PMID- 25748462
TI  - Seeding of mesenchymal stem cells into inner part of interconnected porous
      biodegradable scaffold by a new method with a filter paper.
AB  - An appropriate physical support provided by scaffolds creates a supportive
      environment that directs proliferation and differentiation of stem cells.
      However, it is difficult to homogenously inoculate stem cells into the inner part
      of scaffolds at high cell densities. In this study, mesenchymal stem cells were
      seeded into a hydroxyapatite/poly (D, L-lactic-co-glycolic acid) (HAP/PLGA)
      scaffold that had enough mechanical strength and porous 3-D structure. With an
      aid of a filter paper placed under the bottom of a HAP/PLGA block, the cells
      suspended in a culture medium flowed from the top to the bottom through
      interconnected pores in the scaffold, and distributed almost homogenously, as
      compared to cell distribution near the surface of the block by the conventional
      method using centrifugation or reduced pressure. This simple method with a filter
      paper may be useful in preparation of cell-scaffold complexes for tissue
      engineering. 

PMID- 25748463
TI  - Shear-bond-strength of orthodontic brackets to aged nano-hybrid composite-resin
      surfaces using different surface preparation.
AB  - The aim of this study was to evaluate the effects of different surface
      preparation methods on the shear bond strength (SBS) of orthodontic metal
      brackets to aged nano-hybrid resin composite surfaces in vitro. A total of 100
      restorative composite resin discs, 6 mm in diameter and 3 mm thick, were obtained
      and treated with an ageing procedure. After ageing, the samples were randomly
      divided as follows according to surface preparation methods: (1)Control, (2)37%
      phosphoric acid gel, (3)Sandblasting, (4)Diamond bur, (5)Air-flow and 20 central
      incisor teeth were used for the control etched group. SBS test were applied on
      bonded metal brackets to all samples. SBS values and residual adhesives were
      evaluated. Analysis of variance showed a significant difference (p<0.001) between
      the groups. Sandblasted group had the highest SBS value (12.85 MPa) in
      experimental groups. The sandblasting surface treatment is recommended as an
      effective method of bonding orthodontic metal brackets to nano-hybrid composite
      resin surfaces. 

PMID- 25748464
TI  - Influence of surface treatment of contaminated zirconia on surface free energy
      and resin cement bonding.
AB  - Influences of contamination and cleaning methods on the bonding of resin cement
      to zirconia ceramics were examined. Airborne particle-abraded zirconia (IPS e.max
      ZirCAD) specimens were contaminated with saliva and cleaned with tap water (SC)
      or by application of 37% phosphoric acid (PA), Ivoclean (IC), or additional
      airborne particle abrasion (AB). Specimens without contamination served as
      controls. After application of Monobond Plus to the surface of the specimens,
      resin cement was mixed and inserted into a mold. Surface free energies of the
      specimens were determined by measuring contact angles. Surface treatment and
      storage conditions significantly influenced bond strength, while there was no
      significant interaction between the two factors. Surface free energies of the SC
      and IC groups were significantly lower than those of the other groups. Additional
      AB of saliva-contaminated zirconia increased the strength of bonding with the
      resin cement as well as increased surface free energy. 

PMID- 25748465
TI  - Optical coherence tomography for evaluation of enamel and protective coatings.
AB  - Optical coherence tomography (OCT) is an interferometric imaging technique. This
      study aimed to employ OCT to evaluate four different resin-based materials
      including a coating containing glass-ionomer filler and calcium, a giomer, and
      two fluoride-releasing self-etch resins. The coating and its underlying and
      adjacent enamel were monitored using swept-source OCT (center wavelength: 1330
      nm) at baseline, after 5,000 thermal cycles, and after 1, 4 and 7 days of
      demineralization (pH 4.5). The coatings showed different thicknesses (60-250
      micrometers) and various levels of structural and interfacial integrity. OCT
      could detect a demineralization inhibition zone adjacent to the edge of the
      fluoride- and calcium-releasing material. Localized demineralization was
      occasionally observed under thinner coatings. Protection of susceptible enamel
      surfaces by thin resin-based bioactive coatings provides protection from
      demineralization. OCT can be used to non-destructively monitor the integrity of
      such coatings, as well as enamel changes beneath and adjacent to them. 

PMID- 25748466
TI  - Control of hydroxyapatite crystal growth by gallic acid.
AB  - The purpose of this study is to detect the effect of gallic acid (GA) on
      hydroxyapatie crystal growth and find the mechanism of the regulation. We
      evaluated the morphology of HAP crystals grown under various amounts of GA (0,
      0.05, 1, and 4 gL(-1)). Subsequently, the chemical composition, crystal size and
      the morphology were investigated via the energy-dispersive X-ray spectrometer,
      attenuated total fourier transform infrared spectroscopy, thermogravimetric
      analysis, X-ray diffraction analysis, transmission electron microscope and
      scanning electron microscopy. In all groups, the Ca/P ratio was closed to 1.67.
      In the absence of GA, crystals did not arrange, while in the presence of GA,
      crystals tended to form spherules. The size of the crystals decreased with the
      concentration of GA increased. These results indicated the role of GA on the
      growth and morphology of hydroxyapatite crystals, which might be the key
      mechanism for gallic acid regulating the mineralization. 

PMID- 25748467
TI  - Mechanical properties of orthodontic wires made of super engineering plastic.
AB  - Most orthodontic equipment is fabricated from alloys such as stainless steel, Co
      Cr and Ni-Ti because of their excellent elastic properties. In recent years,
      increasing esthetic demands, metal allergy and interference of metals with
      magnetic resonance imaging have driven the development of non-metallic
      orthodontic materials. In this study, we assessed the feasibility of using three
      super engineering plastics (PEEK, PES and PVDF) as orthodontic wires. PES and
      PVDF demonstrated excellent esthetics, although PEEK showed the highest bending
      strength and creep resistance. PEEK and PVDF showed quite low water absorption.
      Because of recent developments in coloration of PEEK, we conclude that PEEK has
      many advantageous properties that make it a suitable candidate for use as an
      esthetic metal-free orthodontic wire. 

PMID- 25748468
TI  - Influence of various superhydrophilic treatments of titanium on the initial
      attachment, proliferation, and differentiation of osteoblast-like cells.
AB  - The purpose of this study was to investigate the influence of superhydrophilic
      treatments of titanium on the behavior of osteoblastlike cells. Superhydrophilic
      specimens were prepared with sandblast and acid-etching (DW), oxygen plasma
      (Plasma) and ultraviolet light (UV), and were stored in distilled water for 3
      days immediately after these treatments. Specimens stored in air for 3 weeks were
      used as a control Air group. Initial cell attachment, proliferation, alkaline
      phosphatase activity, and osteocalcin secretion of mouse osteoblast-like cells
      MC3T3-E1 were enhanced more on superhydrophilic groups than were Air specimens.
      On confocal laser scanning microscope images of cell morphology, the expression
      of actin filaments was observed on the superhydrophilic groups, whereas
      relatively little actin filament expression was seen on the Air surfaces on all
      culture periods. These results indicate that DW, Plasma, or UV treatment has
      potential for the creation and maintenance of superhydrophilic surfaces and the
      enhancement of the initial attachment, proliferation, and differentiation of
      osteoblast-like cells. 

PMID- 25748469
TI  - Patellar instability factors in isolated medial patellofemoral ligament
      reconstructions--what does the literature tell us? A systematic review.
AB  - BACKGROUND: Many studies have demonstrated good results after medial
      patellofemoral ligament (MPFL) reconstruction for patients with patellar
      instability. The applicability of published studies to the clinical decision
      making process for the individual patient with patellar instability, however, is
      not well elucidated. HYPOTHESIS: There is inconsistency in the reporting of
      preoperative and postoperative variables, which limits the applicability of
      current studies to patients with patellar instability. STUDY DESIGN: Systematic
      review. METHODS: A systematic review of the literature was conducted using the
      search term medial patellofemoral ligament reconstruction to identify studies
      with cohorts of patients with isolated MPFL reconstruction. A combination of
      inclusion and exclusion criteria resulted in 24 studies being reviewed for a
      variety of preoperative demographics, physical examination findings, and imaging
      findings, as well as postoperative outcomes, including redislocation and
      responses to subjective questionnaires. RESULTS: A physical examination of
      lateral patellar translation was reported in 42% of studies, by reporting an
      apprehension sign (n = 9), reporting quadrant translation (n = 7), or both. For
      patellar instability factors on imaging, patellar height was reported as a
      preoperative variable in 75% of studies, and trochlear dysplasia was reported in
      83% of studies. The tibial tubercle-trochlear groove distance was reported as a
      preoperative variable in 42% of studies. The rate of redislocation after index
      surgery was reported in 92% of studies. Patient-related outcome measures were
      reported in all of the studies; the Kujala score was the most common. A
      homogeneous population was selected as part of the authors' surgical indications
      for "isolated" MPFL in 67% of studies, and a heterogeneous population was
      selected in 33% of studies. CONCLUSION: Current literature on MPFL reconstruction
      contains diverse methods of recording preoperative and postoperative variables.
      Most studies report on a homogeneous population, with inconsistent applicability
      to the broad spectrum of patients with patellar instability. Outcomes reporting
      in our current literature needs more clarity and consistency regarding reporting
      methodology to be of value for the treating clinician.

PMID- 25748470
TI  - Identifying sex-specific risk factors for low bone mineral density in adolescent
      runners.
AB  - BACKGROUND: Adolescent runners may be at risk for low bone mineral density (BMD)
      associated with sports participation. Few prior investigations have evaluated
      bone health in young runners, particularly males. PURPOSE: To characterize sex
      specific risk factors for low BMD in adolescent runners. STUDY DESIGN: Cross
      sectional study; Level of evidence, 3. METHODS: Training characteristics,
      fracture history, eating behaviors and attitudes, and menstrual history were
      measured using online questionnaires. A food frequency questionnaire was used to
      identify dietary patterns and measure calcium intake. Runners (female: n = 94,
      male: n = 42) completed dual-energy x-ray absorptiometry (DXA) to measure lumbar
      spine (LS) and total body less head (TBLH) BMD and body composition values,
      including android-to-gynoid (A:G) fat mass ratio. The BMD was standardized to Z
      scores using age, sex, and race/ethnicity reference values. Questionnaire values
      were combined with DXA values to determine risk factors associated with
      differences in BMD Z-scores in LS and TBLH and low bone mass (defined as BMD Z
      score <=-1). RESULTS: In multivariable analyses, risk factors for lower LS BMD Z
      scores in girls included lower A:G ratio, being shorter, and the combination of
      (interaction between) current menstrual irregularity and a history of fracture
      (all P < .01). Later age of menarche, lower A:G ratio, lower lean mass, and
      drinking less milk were associated with lower TBLH BMD Z-scores (P < .01). In
      boys, lower body mass index (BMI) Z-scores and the belief that being thinner
      improves performance were associated with lower LS and TBLH BMD Z-scores (all P <
      .05); lower A:G ratio was additionally associated with lower TBLH Z-scores (P <
      .01). Thirteen girls (14%) and 9 boys (21%) had low bone mass. Girls with a BMI
      <=17.5 kg/m(2) or both menstrual irregularity and a history of fracture were
      significantly more likely to have low bone mass. Boys with a BMI <=17.5 kg/m(2)
      and belief that thinness improves performance were significantly more likely to
      have low bone mass. CONCLUSION: This study identified sex-specific risk factors
      for impaired bone mass in adolescent runners. These risk factors can be helpful
      to guide sports medicine professionals in evaluation and management of young
      runners at risk for impaired bone health.

PMID- 25748471
TI  - Placement of Double Tunnels in ACL Reconstruction Using Bony Landmarks Versus
      Existing Footprint Remnant: A Prospective Clinical Study With 2-Year Follow-up.
AB  - BACKGROUND: The outcomes of double-bundle anterior cruciate ligament
      reconstruction (DB-ACLR) are becoming controversial. One of the main reasons for
      the controversy is the techniques for bone tunnel placement. The common technique
      to place the bone tunnels is to use bony landmarks, while a new approach uses
      footprint remnants. PURPOSE: To investigate if placement of double tunnels using
      bony landmarks produces the same clinical results as that of using existing
      footprint remnants. STUDY DESIGN: Randomized controlled trial; Level of evidence,
      2. METHODS: A total of 72 male patients were randomly divided into 2 groups of 36
      patients each: (A) DB-ACLR tunnel placement using the footprint remnant procedure
      (EF group) and (B) DB-ACLR tunnel placement using the bony landmark procedure (BL
      group). All patients were evaluated before and after surgery. Outcomes were
      measured by KT-2000 arthrometer side-to-side difference, pivot-shift test, and
      Tegner, Lysholm, and International Knee Documentation Committee (IKDC) scores.
      Second-look arthroscopic evaluations were performed in 59 cases (28 and 31 cases
      in the EF and BL groups, respectively). RESULTS: The mean follow-up time was
      36.9+/-4.8 months. Postoperative 3-dimensional computed tomography scans showed
      that bone sockets were variable on both femoral and tibial sides in the EF group
      and almost consistent in the BL group. All of the evaluation indexes were
      significantly improved postoperatively in both groups. There were no revision
      cases in the EF group and 2 in the BL group. The EF group showed a faster range
      of motion (ROM) recovery (at 0 degrees  to 120 degrees ) than did the BL group.
      At final follow-up, there was no significant difference between the EF and BL
      groups in Tegner score (5.88+/-1.39 vs 5.16+/-1.76; P=.058) or pivot-shift test
      (34 vs 32; P=.067). The EF group had a larger proportion of patients with IKDC
      grade A (normal) (33 vs 24; P<.020), smaller side-to-side difference (0.68+/-0.38
      mm vs 1.23+/-0.61 mm; P<.001), higher Lysholm score (91.29+/-4.90 vs 88.71+/
      5.09; P=.032), and better second-look arthroscopic evaluations for graft quality
      in the anteromedial (P=.034), posterolateral (P=.015), and combined bundles
      (P=.029) compared with the BL group. CONCLUSION: Although both techniques
      provided satisfactory clinical results, DB-ACLR using the existing footprint
      remnant for tunnel placement showed better functional results with respect to
      faster ROM recovery, higher subjective outcome scores, and better arthroscopic
      second-look with no revision cases.

PMID- 25748472
TI  - Bone fragment union and remodeling after arthroscopic bony bankart repair for
      traumatic anterior shoulder instability with a glenoid defect: influence on
      postoperative recurrence of instability.
AB  - BACKGROUND: Although good clinical outcomes have been reported after arthroscopic
      bony Bankart repair, the extent of bone union is still unclear. PURPOSE: To
      investigate bone union after arthroscopic bony Bankart repair and its influence
      on postoperative recurrence of instability. STUDY DESIGN: Cohort study; Level of
      evidence, 3. METHODS: Among 113 consecutive shoulders that underwent arthroscopic
      bony Bankart repair, postoperative evaluation of bone union by computed
      tomography (CT) was performed at various times in 81 shoulders. Bone union was
      investigated during 3 periods: 3 to 6 months postoperatively (first period), 7 to
      12 months postoperatively (second period), and 13 months or more postoperatively
      (third period). The influence of the size of the preoperative glenoid defect and
      the size of the bone fragment on bone union was investigated, as well as the
      influence of bone union on postoperative recurrence of instability. In shoulders
      with bone union, bone fragment remodeling and changes in the glenoid defect size
      were also investigated. RESULTS: The bone union rate was 30.5% in the first
      period, 55.3% in the second period, and 84.6% in the third period. Among 53
      shoulders with CT evaluation in the second period or later and follow-up for a
      minimum of 1 year, there was complete union in 33 shoulders (62.3%), partial
      union in 3 (5.7%), nonunion in 8 (15.1%), and no fragment on CT in 9 (17.0%). The
      complete union rate was 50% for 22 shoulders with small bone fragments (<5% of
      the glenoid diameter), 56.3% for 16 shoulders with medium fragments (5%-10%), and
      86.7% for 15 shoulders with large fragments (>10%). The recurrence rate for
      postoperative instability was only 6.1% for shoulders with complete union, while
      it was 50% for shoulders with partial union, nonunion, no fragment, and no
      fragment on CT. The recurrence rate was significantly higher (36.4%) in shoulders
      with small fragments, but it was significantly lower in shoulders with bone
      union. In shoulders with bone union, the bone fragment frequently became larger
      over time, while the size of the glenoid defect decreased significantly from
      18.6% preoperatively to 4.7% postoperatively. CONCLUSION: Bone union was not
      always achieved after arthroscopic bony Bankart repair, and union was often
      delayed. Recurrence of instability was significantly more frequent when bone
      union failed. The size of the glenoid defect decreased significantly in shoulders
      with bone union.

PMID- 25748473
TI  - No association between fibrosis on magnetic resonance imaging at return to play
      and hamstring reinjury risk.
AB  - BACKGROUND: Connective tissue scar (fibrosis) is a common finding on magnetic
      resonance imaging (MRI) after recovery from acute hamstring injuries. Fibrosis
      has been suggested as a predisposing factor for reinjury, but evidence from
      clinical studies is lacking. PURPOSE/HYPOTHESIS: The aim of this study was to
      examine the association between the presence of fibrosis on MRI at return to play
      after an acute hamstring injury and the risk of reinjury. The hypothesis was that
      fibrous tissue on MRI was associated with an increased reinjury risk. STUDY
      DESIGN: Cohort study; Level of evidence, 3. METHODS: Magnetic resonance images
      were obtained from 108 consecutive athletes with modified Peetrons classification
      grade 1 or 2 hamstring injuries within 5 days of injury and within 7 days of
      return to play. The presence and extent of abnormally low signal intensity in the
      intramuscular tissue on MRI, suggestive of fibrosis, were assessed on both T1-
      and T2-weighted images. Reinjuries were recorded over a 1-year follow-up period.
      The association between fibrosis and reinjury risk was analyzed with a Cox
      proportional hazards model. RESULTS: The MRIs of the initial injury showed 45
      (43%) grade 1 and 63 (57%) grade 2 injuries. Median time of return to play was 30
      days (interquartile range [IQR], 22-42 days). At return to play, 41 athletes
      (38%) had fibrosis on MRI with a median longitudinal length of 5.8 cm (IQR, 3.3
      12.5 cm) and a median volume of 1.5 cm3 (IQR, 1.5-3.9 cm3). In athletes with
      fibrosis, 24% (10/41) sustained a reinjury, and in the subjects without fibrosis,
      24% (16/67) had a reinjury, resulting in a hazard ratio of 0.95 (95% CI, 0.43
      2.1; P=.898). CONCLUSION: Fibrosis is commonly seen on MRI at return to play
      after grade 1 or 2 hamstring injuries but is not associated with reinjury risk.

PMID- 25748474
TI  - Magnetic resonance imaging of a small vessel hepatic hemangioma in a cirrhotic
      patient with histopathologic correlation.
AB  - The authors report and discuss a rare case of a small vessel hepatic hemangioma
      in a 59-year-old patient with liver cirrhosis, which was pre-procedurally
      characterized as indeterminate due to atypical magnetic resonance imaging (MRI)
      features. This manuscript reviews the MRI features with pathologic correlation,
      emphasizes the importance of accurate characterization of liver lesions, and
      discusses the role of biopsy. We believe this is the first reported case of a
      small vessel hemangioma in liver cirrhosis with imaging and histopathologic
      correlation. 

PMID- 25748475
TI  - After critical care: patient support after critical care. A mixed method
      longitudinal study using email interviews and questionnaires.
AB  - PURPOSE: To explore experiences and needs over time, of patients discharged from
      ICU using the Intensive Care Experience (ICE-q) questionnaire, Hospital Anxiety
      and Depression Scale (HADS) and EuroQoL (EQ-5D), associated clinical predictors
      (APACHE II, TISS, Length of stay, RIKER scores) and in-depth email interviewing.
      METHODS: A mixed-method, longitudinal study of patients with >48hour ICU stays at
      2 weeks, 6 months, 12 months using the ICE-q, HADS, EQ-5D triangulated with
      clinical predictors, including age, gender, length of stay (ICU and hospital),
      APACHE II and TISS. In-depth qualitative email interviews were completed at 1
      month and 6 months. Grounded Theory analysis was applied to interview data and
      data were triangulated with questionnaire and clinical data. RESULTS: Data was
      collected from January 2010 to March 2012 from 77 participants. Both mean EQ-5D
      visual analogue scale, utility scores and HADS scores improved from 2 weeks to 6
      months, (p=<0.001; p=<0.001), but between 6 and 12 months, no change was found in
      data from either questionnaire, suggesting improvements level off. These
      variations were reflected in qualitative data themes: rehabilitation/recovery in
      the context of chronic illness; impact of critical care; emotional and
      psychological needs (including sub-themes of: information needs and relocation
      anxiety). The overarching, core theme related to adjustment of normality.
      CONCLUSIONS: Patient recovery in this population appears to be shaped by ongoing
      illness and treatment. Email interviews offer a convenient method of gaining in
      depth interview data and could be used as part of ICU follow-up.

PMID- 25748476
TI  - Anatomic Variation of Facial Vein in Carotid-Cavernous Fistula and Trans-Facial
      Vein Embolization.
AB  - OBJECTIVE: Trans-facial vein (FV) embolization via the internal jugular vein is
      an alternative approach to embolization of carotid cavernous fistulas (CCFs). The
      purpose of this study is to report the anatomic variation of FVs and our
      experience of trans-FV embolization of CCFs. METHODS: Over 6 years, 26 patients
      (12 men and 14 women; age range 27-72 years old) with CCFs underwent trans-FV
      embolization because of anterior drainage of fistulas. We retrospectively
      analyzed angioarchitecture of the CCFs focusing on the anatomic variations of FVs
      and angiographic and clinical outcomes after embolization. RESULTS: FVs drained
      to the internal jugular vein in 10 (38%) cases; FVs unexpectedly emptied into the
      external jugular vein in 16 (62%) cases. All FVs entered into the internal
      jugular vein at the level of the hyoid bone. In cases with fistulas to the FV and
      EJV, the termination of FVs was variable including superior (n = 5), inferior (n
      = 1), or at the level of the hyoid bone (n = 10). Successful microcatheterization
      via different insertions of FVs to jugular veins was achieved in all cases. One
      patient had a small residual fistula, and 2 patients had fistula recurrence.
      Temporary impairment of cranial nerve III or VI occurred in 4 patients. The mean
      clinical follow-up time was 18 months. CONCLUSIONS: Trans-FV embolization is an
      effective and safe method to manage CCFs with anterior drainage. However,
      anatomic variations of the FV exist, and a careful work-up of fistula venous
      drainage before trans-FV embolization is essential to reduce erroneous attempts,
      procedure time, and periprocedural risk.

PMID- 25748477
TI  - A Predictive Model of Unfavorable Outcomes After Benign Intracranial Tumor
      Resection.
AB  - BACKGROUND: Benchmarking of outcomes and individualized risk prediction are
      central in patient-oriented shared decision making. We attempted to create a
      predictive model of complications in patients undergoing benign intracranial
      tumor resection. METHODS: We performed a retrospective cohort study involving
      patients who underwent craniotomies for benign intracranial tumor resection
      during the period 2005-2011 and were registered in the National (Nationwide)
      Inpatient Sample database. A model for outcome prediction based on individual
      patient characteristics was developed. RESULTS: There were 19,894 patients who
      underwent benign tumor resection. The respective inpatient postoperative
      incidences were 1.3% for death, 22.7% for unfavorable discharge, 4.2% for treated
      hydrocephalus, 1.1% for cardiac complications, 0.9% for respiratory
      complications, 0.5% for wound infection, 0.5% for deep venous thrombosis, 2.3%
      for pulmonary embolus, and 1.5% for acute renal failure. Multivariable analysis
      identified risk factors independently associated with the above-mentioned
      outcomes. A model for outcome prediction based on patient and hospital
      characteristics was developed and subsequently validated in a bootstrap sample.
      The models demonstrated good discrimination with areas under the curve of 0.85,
      0.76, 0.72, 0.74, 0.72, 0.74, 0.76, 0.68, and 0.86 for postoperative risk of
      death, unfavorable discharge, hydrocephalus, cardiac complications, respiratory
      complications, wound infection, deep venous thrombosis, pulmonary embolus, and
      acute renal failure. The models also had good calibration, as assessed by the
      Hosmer-Lemeshow test. CONCLUSIONS: Our models can provide individualized
      estimates of the risks of postoperative complications based on preoperative
      conditions and potentially can be used as an adjunct for decision making in
      benign intracranial tumor surgery.

PMID- 25748478
TI  - Live birth and cumulative live birth rates in expected poor ovarian responders
      defined by the Bologna criteria following IVF/ICSI treatment.
AB  - OBJECTIVE: To determine the live birth and cumulative live birth rates of
      expected poor ovarian responders according to the Bologna criteria and to compare
      their outcomes with those of expected normal responders. DESIGN: Retrospective
      analysis. SETTING: University infertility clinic. PATIENTS: A total of 1,152
      subfertile women undergoing their first in vitro fertilization (IVF) cycle.
      INTERVENTIONS: Women were classified into 4 groups according to the Bologna
      criteria for comparison. MAIN OUTCOME MEASURE(S): Live birth and cumulative live
      birth rates. RESULTS: Women with expected poor response (POR) had the lowest live
      birth rate than the other 3 groups (23.8%, p = 0.031). Cumulative live birth
      rates were significantly lower in those with expected POR than those with
      expected normal ovarian response (NOR) (35.8% vs 62.8%, p<0.0001). In the
      subgroup analysis, the cumulative live birth rates in expected PORs were
      significantly lower in those who had <=3 oocytes retrieved (18.6% for <=3 oocytes
      vs 44.0% for >3 oocytes, p = 0.006) whereas the live birth rates in fresh cycle
      did not differ (17.8% vs 30.9%, p = 0.108). CONCLUSION: Women who were expected
      POR according to the Bologna criteria had lower live birth and cumulative live
      birth than expected NOR but they still can achieve reasonable treatment outcomes
      and IVF treatment should not be precluded.

PMID- 25748479
TI  - Improving Care for Lesbian, Gay, Bisexual, and Transgender Patients in the
      Emergency Department.

PMID- 25748480
TI  - Quantifying Patient-Physician Communication and Perceptions of Risk During
      Admissions for Possible Acute Coronary Syndromes.
AB  - STUDY OBJECTIVE: Disposition decision for patients with possible acute coronary
      syndrome in the emergency department (ED) is driven primarily by perception of
      short-term risks. We sought to evaluate communication between patient and
      physician about these risks by ascertaining the content of discussions
      surrounding disposition decision. METHODS: We conducted matched-pair surveys of
      patients admitted for possible acute coronary syndrome and their physicians in 2
      academic, inner-city EDs. After disposition conversation, trained research
      assistants administered surveys querying perceived and communicated risk
      estimates and purpose of admission. Primary exclusion criteria were ECG or
      troponin value diagnostic of acute coronary syndrome. The primary outcome measure
      was agreement in assessment of the risk of myocardial infarction, defined as the
      proportion of patient-physician pairs whose risk estimates were within 10% of
      each other. RESULTS: A total of 425 patient-physician survey pairs were
      collected. Fifty-three percent of patients were men. Patients reported discussing
      the likelihood of their symptoms' being due to myocardial infarction in 65% of
      cases, whereas physicians reported this in 46%. After their discussion,
      physicians' (n=415) median estimate of short-term risk was 5% (95% confidence
      interval [CI] 3% to 7%), whereas patients' (n=401) was 8% (95% CI 5% to 11%).
      Most patients (63%; 95% CI 57% to 67%) reported that this estimate remained the
      same or increased after their conversation. Risk agreement within 10% occurred in
      36% of cases (n=404; 95% CI 32% to 41%). Patients' median estimates of the
      mortality of myocardial infarction at home versus in the hospital were 80%
      (n=398; 95% CI 76% to 84%) and 10% (n=390; 95% CI 7% to 13%), respectively,
      whereas physician estimates were 15% (n=403; 95% CI 12% to 18%) and 10% (n=398;
      95% CI 7% to 13%). CONCLUSION: Our survey demonstrates poor communication, with
      overestimation of both the risks of myocardial infarction and potential benefit
      of hospital admission. These findings suggest that communication surrounding
      disposition decisions in chest pain patients may at times be ineffective or
      misleading.

PMID- 25748481
TI  - Correction: Simulating the real origins of communication.

PMID- 25748482
TI  - Health-related quality of life and happiness within an internal medicine
      residency training program: a longitudinal follow-up study.
AB  - PURPOSE: While undergoing a hospital residency training program, residents often
      suffer anxiety and stress. This study aims to evaluate the change in health
      related quality of life and happiness among internal medicine residents, and
      identify prognostic factors. METHODS: Thirty-eight residents in the Ramathibodi
      Hospital internal medicine training program completed the World Health
      Organization Quality of Life-BREF and happiness Measures questionnaires at three
      time points: commencement, day 100, and the end of the second year of training.
      Confidence, expectations, anxiety, and general health were rated. Analyses were
      performed with mixed linear regression. RESULTS: Financial problems were reported
      for 16 residents (42.1%). At baseline, most residents had moderate-to-very high
      confidence, expectations, and general health but also moderate-to-very high
      anxiety. The health-related quality of life score was highest in the social
      domain followed by the environmental, psychological, and physical domains. Their
      psychological, physical, social, and environmental scores significantly decreased
      after enrollment. Their happiness and general health scores were significantly
      reduced after enrollment. The training program duration was negatively associated
      with all domains. Residents with greater confidence had higher health-related
      quality of life scores in the physical, psychological, and environmental domains.
      Moreover, their general health was positively associated with the social and
      environmental domains. CONCLUSION: A reduction in health-related quality of life
      and happiness under the internal medicine residency program is reported. High
      confidence and good physical health may counterbalance the decline in health
      related quality of life and happiness.

PMID- 25748483
TI  - Optimism, well-being, and perceived stigma in individuals living with HIV.
AB  - Given the significant psychological challenges posed by HIV-related stigma for
      individuals living with HIV, investigating psychological resource factors for
      coping with HIV-related stigma is important. Optimism, which refers to
      generalized expectations regarding favorable outcomes, has been associated with
      enhanced psychological adaptation to health conditions, including HIV. Therefore,
      this cross-sectional study investigated associations among optimism,
      psychological well-being, and HIV stigma in a sample of 116 adults living with
      HIV and seeking mental health services. Consistent with study hypotheses,
      optimism was positively associated with psychological well-being, and
      psychological well-being was negatively associated with HIV-related stigma.
      Moreover, results of a full structural equation model suggested a mediation
      pattern such that as optimism increases, psychological well-being increases, and
      perceived HIV-related stigma decreases. The implications of these findings for
      clinical interventions and future research are discussed.

PMID- 25748484
TI  - A novel syndrome of Klippel-Feil anomaly, myopathy, and characteristic facies is
      linked to a null mutation in MYO18B.
AB  - BACKGROUND: Klippel-Feil anomaly (KFA) can be seen in a number of syndromes. We
      describe an apparently novel syndromic association with KFA. METHODS: Clinical
      phenotyping of two consanguineous families followed by combined autozygome/exome
      analysis. RESULTS: Two patients from two apparently unrelated families shared a
      strikingly similar phenotype characterised by KFA, myopathy, mild short stature,
      microcephaly, and distinctive facies. They shared a single founder autozygous
      interval in which whole exome sequencing revealed a truncating mutation in
      MYO18B. There was virtually complete loss of the transcript in peripheral blood,
      indicative of nonsense-mediated decay. Electron microscopy of muscle confirms
      abnormal myosin filaments with accompanying myopathic changes. CONCLUSIONS:
      Deficiency of MYO18B is linked to a novel developmental disorder which combines
      KFA with myopathy. This suggests a widespread developmental role for this gene in
      humans, as observed for its murine ortholog.

PMID- 25748485
TI  - Ixekizumab for treatment of psoriasis.
AB  - Psoriasis is a prevalent chronic inflammatory skin disease of unknown etiology.
      Recent advances in understanding the pathogenesis of psoriasis suggest that IL-17
      is a key proinflammatory mediator present in the skin. Several agents targeting
      IL-17 or its receptor are in clinical trials for the treatment of psoriasis. This
      review focuses on the biological rationale and the results of clinical trials
      with ixekizumab, a humanized IgG4 monoclonal antibody. Ixekizumab binds the IL
      17A homodimer, thereby blocking the binding of IL-17A to the IL-17 receptor. The
      currently available Phase I-III data indicate that ixekizumab is a promising
      drug, although long-term data of efficacy and safety are needed before ixekizumab
      and other IL-17 targeting therapeutics can find their place in clinical practice.

PMID- 25748486
TI  - Prediction of adherent placenta in pregnancy with placenta previa using
      ultrasonography and magnetic resonance imaging.
AB  - OBJECTIVE: Adherent placenta is a life-threatening condition in pregnancy, and is
      often complicated by placenta previa. The aim of this prospective study was to
      determine prenatal imaging findings that predict the presence of adherent
      placenta in pregnancies with placenta previa. STUDY DESIGN: The study included 58
      consecutive pregnant women with placenta previa who underwent both
      ultrasonography and magnetic resonance imaging prenatally. Ultrasonographic
      findings of anterior placental location, grade 2 or higher placental lacunae
      (PL>=G2), loss of retroplacental hypoechoic clear zone (LCZ) and the presence of
      turbulent blood flow in the arteries were evaluated, in addition to MRI findings.
      Forty-three women underwent cesarean section alone; 15 women with adherent
      placenta underwent cesarean section followed by hysterectomy with pathological
      examination. To determine imaging findings that predict adherent placenta,
      univariate and multivariate logistic regression analyses were performed. RESULTS:
      Univariate logistic regression analyses demonstrated that anterior placental
      location, PL>=G2, LCZ, and MRI were associated with the presence of adherent
      placenta. Multivariate analyses revealed that LCZ (p<0.01, odds ratio 15.6, 95%CI
      2.1-114.6) was a single significant predictor of adherent placenta in women with
      placenta previa. CONCLUSION: This prospective study demonstrated for the first
      time that US findings, especially LCZ, might be useful for identifying patients
      at high risk for adherent placenta among pregnant women with placenta previa.

PMID- 25748487
TI  - Change of steroid receptor expression in the posterior vaginal wall after local
      estrogen therapy.
AB  - Little is known about the reaction of the posterior vaginal wall influenced by
      steroid receptor expression. The aim of our study was to evaluate change of
      estrogen and progesterone receptor expression in the posterior vaginal wall after
      local estrogen therapy for vaginal prolapse surgery and to compare this
      expression with a group of untreated women of same age. Furthermore we examined
      the steroid receptor expression among untreated women in each period of life. In
      a prospective clinical study we examined staining intensity and ratio of positive
      cytoblasts in specimens of vaginal tissue sampled during posterior colporrhaphy
      and as control group specimens from autopsied corpses to proof the change in
      steroid receptor expression in treated women after local estrogen therapy
      compared to treatment-naive women of all ages. We compared 60 premenopausal
      female corpses to 43 postmenopausal female corpses and 80 postmenopausal women
      undergoing posterior colporrhaphy to 43 postmenopasusal female corpses. Estrogen
      receptor alpha score was significantly higher in the intervention group in basal
      epithelium (p=0.004), stroma (p<=0.001) and connective tissue (p=0.005). Estrogen
      receptor beta score was significantly higher in basal epithelium (p=0.048),
      progesterone-receptor score was significantly higher in the intervention group in
      stroma and connective tissue (p<=0.001) and in superficial epithelium (p=0.017).
      Local vaginal estrogen therapy leads to increase in estrogen-receptor alpha and
      progesterone-receptor expression of the posterior vaginal wall in postmenopausal
      women, while estrogen-receptor-beta-expression keeps nearly unchanged. This
      explains the fact that proliferation of the vaginal tissue is mediated by
      estrogen-receptor alpha and improves the condition for our prolapse surgery. 

PMID- 25748488
TI  - Satisfaction, quality of life and lumbar pain following laparoscopic
      sacrocolpopexy: suture vs. tackers.
AB  - OBJECTIVE: To compare the operative results and rate of complications, in
      particular dorsolumbar pain, following laparoscopic sacrocolpopexy (LS) using
      sutures or tackers. STUDY DESIGN: A case-control study: LS using tackers (n=35,
      tacker group) compared with LS using sutures (n=65, suture group). In addition to
      clinical evaluation of prolapse, all patients were evaluated for urinary
      incontinence (ICIQ-SF), dorsolumbar pain, overall quality of life (SF-36 score),
      and overall improvement in symptoms (PGI-I), one year after LS. RESULTS: The
      patient characteristics (age, initial stage of prolapse,...) were comparable in
      the two groups, as was operating time (240 vs. 210min, p=0.18). There was no
      significant between-group difference in terms of anatomical correction (median
      post-operative ICS stage: 0 in both groups, p=0.26) or post-operative
      complication rates. The incidence of de novo low back pain appearing after LS was
      equivalent in both groups (50% vs. 25%, in the tacker and suture groups,
      respectively, p=0.11). However, there was a significant difference in lumbar pain
      intensity evaluated using the visual analog scale (4 (IQR 0-6.5) vs. 0 (IQR 0-4)
      in the tacker and suture groups, respectively; p=0.01), and in post-operative
      quality of life, which was better in patients in the suture group according to
      all the questionnaires. CONCLUSION: Our study suggests that the use of tackers
      for prosthesis fixation to the promontory does not increase the incidence of post
      operative dorsolumbar pain, but may increase its intensity and decrease quality
      of life.

PMID- 25748489
TI  - Impact of risk factors other than prematurity on periventricular leukomalacia. A
      population-based matched case control study.
AB  - OBJECTIVE: Periventricular leukomalacia (PVL) is a neonatal brain white matter
      injury associated with development of cerebral palsy, intellectual impairment,
      and visual disturbances. PVL is more common in premature neonates. Our objective
      was to examine the impact of several potential risk factors other than
      prematurity on the incidence of PVL. STUDY DESIGN: A case-control study based on
      the Slovenian National Perinatal Information System data for the period 2002
      2011. All singleton and twin pregnancies delivered at >=22 weeks' in Slovenia
      during the study period were included. Cases were pregnancies with PVL in at
      least one neonate. For each pregnancy in the case cohort, three pregnancies
      matched by gestational age and plurality were selected. Chi-square test was used
      to examine the associations between PVL and several potential risk factors:
      maternal age, pre-pregnancy body-mass-index, preexisting diabetes, gestational
      diabetes, pregnancy after in-vitro-fertilization, severe preeclampsia, vaginal
      delivery, no steroid therapy prior to delivery, small for gestational age, and
      fetal-inflammatory-response-syndrome. P<0.05 was considered statistically
      significant. RESULTS: One lakh ninety one thousand and eighty three singleton and
      3377 twin pregnancies delivered at >=22 weeks' in Slovenia during the study
      period. PVL was diagnosed in 86 singletons (0.045%) and 25 twins (0.74%). In all
      twin pregnancy cases only one twin was diagnosed with PVL. 258 singleton and 75
      twin controls were matched to the 86 singleton and 25 twin cases. Of all risk
      factors studied, only maternal obesity and chorioamnionitis were significantly
      associated with PVL. CONCLUSION: Maternal obesity and chorioamnionitis increase
      the risk of PVL beyond that expected solely from prematurity.

PMID- 25748490
TI  - Geranylgeranylacetone ameliorates lung ischemia/reperfusion injury by HSP70 and
      thioredoxin redox system: NF-kB pathway involved.
AB  - Geranylgeranylacetone (GGA) has been clinically used as an anti-ulcer drug. In
      the present study, we explored the protective effects of GGA on lung
      ischemia/reperfusion injury (IRI) and the underlying mechanism. The results
      demonstrated that GGA ameliorated the lung biochemical and histological
      alterations induced by IRI, which was reversed by HSP70 inhibition. To further
      explore the mechanism of GGA action, we focused on NF-kB and thioredoxin (Trx)
      redox system. It was shown that GGA induced the HSP70 and Trx-1 expression, NF-kB
      nuclear translocation and activated thioredoxin reductase (TrxR). The Trx-1
      expression and TrxR activity was suppressed by HSP70 and NF-kB inhibition, while
      the nuclear NF-kB p65 expression was suppressed by HSP70 inhibitor. These results
      indicated that GGA may protect rat lung against IRI by HSP70 and Trx redox
      system, in which NF-kB pathway may be involved. 

PMID- 25748491
TI  - Effect of repeated simulated clinical use and sterilization on the cutting
      efficiency and flexibility of Hyflex CM nickel-titanium rotary files.
AB  - INTRODUCTION: Recent nickel-titanium manufacturing processes have resulted in an
      alloy that remains in a twinned martensitic phase at operating temperature. This
      alloy has been shown to have increased flexibility with added tolerance to cyclic
      and torsional fatigue. The aim of this study was to assess the effect of repeated
      simulated clinical use and sterilization on cutting efficiency and flexibility of
      Hyflex CM rotary files. METHODS: Cutting efficiency was determined by measuring
      the load required to maintain a constant feed rate while instrumenting simulated
      canals. Flexibility was determined by using a 3-point bending test. Files were
      autoclaved after each use according to the manufacturer's recommendations. Files
      were tested through 10 simulated clinical uses. For cutting efficiency, mean data
      were analyzed by using multiple factor analysis of variance and the Dunnett post
      hoc test (P < .05). For flexibility, mean data were analyzed by using Levene's
      Test of Equality of Error and a general linear model (P < .05). RESULTS: No
      statistically significant decrease in cutting efficiency was noted in groups 2,
      5, 6, and 7. A statistically significant decrease in cutting efficiency was noted
      in groups 3, 4, 8, 9, and 10. No statistically significant decrease in
      flexibility was noted in groups 2, 3, and 7. A statistically significant decrease
      in flexibility was noted in groups 4, 5, 6, 8, 9, 10, and 11. CONCLUSIONS:
      Repeated simulated clinical use and sterilization showed no effect on cutting
      efficiency through 1 use and no effect on flexibility through 2 uses.

PMID- 25748492
TI  - C-reactive protein expression is up-regulated in apical lesions of endodontic
      origin in association with interleukin-6.
AB  - INTRODUCTION: C-reactive protein (CRP) is the prototype component of acute-phase
      proteins induced ultimately by interleukin (IL)-6 in the liver, but it is unknown
      whether periradicular tissues locally express CRP. The present study aimed to
      identify whether CRP messenger RNA synthesis occurs in situ within apical lesions
      of endodontic origin (ALEOs) and healthy periodontal ligament and its association
      with IL-6 and to determine their protein levels and tissue localization. METHODS:
      Patients with asymptomatic apical periodontitis and healthy volunteers presenting
      at the School of Dentistry, University of Chile, Santiago, Chile, were enrolled.
      ALEOs and healthy teeth were obtained and processed for either
      immunohistochemistry and double immunofluorescence to assess IL-6 and CRP tissue
      localization, whereas healthy periodontal ligaments were processed as controls
      for real-time reverse-transcription polymerase chain reaction for their RNA
      expression levels and multiplex assay to determine their protein levels.
      Statistic analysis was performed using the unpaired t test or Mann-Whitney test
      according to data distribution and Pearson correlation. RESULTS: IL-6 and CRP
      were synthesized in ALEOs, whereas their RNA expression and protein levels were
      significantly higher when compared with healthy periodontal ligament. IL-6 and
      CRP immunolocalized to the inflammatory cells, vascular endothelial cells, and
      mesenchymal cells. Both, IL-6 and CRP colocalized in ALEOs, and a positive
      correlation was found between their expression levels (P < .05). CONCLUSIONS: IL
      6 and CRP messenger RNA are constitutively expressed in periodontal ligament and
      up-regulated in ALEOs along with higher protein levels. Given their pleiotropic
      effects, IL-6 and CRP protein levels in apical tissues might partially explain
      the development and progression of ALEOs as well as potentially asymptomatic
      apical periodontitis-associated systemic low-grade inflammation.

PMID- 25748493
TI  - Distribution of genes related to antimicrobial resistance in different oral
      environments: a systematic review.
AB  - INTRODUCTION: The oral cavity is the main source of microorganisms for
      odontogenic infections. It is important to perform an extensive analysis
      regarding the reports on the presence of bacteria that carry resistance genes to
      antimicrobial agents. The aim of the study was to verify the reports on the
      distribution of genes associated with resistance to antibiotics prescribed in
      dentistry in different human oral sites. METHODS: A systematic review was
      conducted in electronic databases and gray literature to analyze clinical studies
      that detected genes of bacterial resistance to antibiotics in saliva,
      supragingival biofilm, and endodontic infections. Data regarding the research
      group, geographic location, sample source, number of subjects, methods for sample
      analysis, the targeted gene groups, and the detection rates were collected.
      Descriptive data analysis was performed. RESULTS: Preliminary analysis was
      performed in 152 titles; 50 abstracts were reviewed, and 29 full texts were
      obtained. Nine articles matched the inclusion criteria (saliva = 2, supragingival
      biofilm = 1, and endodontic infections = 6). The presence of 33 different
      targeted genes was evaluated. The most frequently investigated groups of genes
      were tetracycline and lactamics (tetM, tetQ, tetW, and cfxA). There was a wide
      range for the detection rates of each resistance gene among studies and for each
      specific gene group. CONCLUSIONS: This systematic review highlights the presence
      of resistance genes to antimicrobial agents in saliva, dental biofilm, and
      endodontic infections, especially for tetracycline and lactamics. There is a lack
      of reports on the presence of genes and resulting outcomes obtained through the
      therapeutic approaches for infection control.

PMID- 25748495
TI  - Debridement, antibiotics and implant retention in early postoperative infection
      with Enterococcus sp.

PMID- 25748494
TI  - Antifungal stewardship in a tertiary-care institution: a bedside intervention.
AB  - Antifungal stewardship (AFS) programmes are needed in tertiary-care hospitals.
      Our aim is to describe a bedside non-restrictive AFS programme, and to evaluate
      its economic impact. During the first year of the AFS a bundle of non
      interventional measures were implemented. During the second year an infectious
      diseases specialist visited 453 patients receiving candins, liposomal
      amphotericin B, voriconazole or posaconazole. Monthly costs were studied with an
      interrupted time series (ITS) analysis. The main prescribing departments were
      haematology (35%), medical departments (23%), and intensive care units (20%).
      Reasons to start antifungal therapy were: targeted therapy (36%), prophylaxis
      (32%), empirical therapy (20%) and pre-emptive therapy (12%). At the initial
      visit, diagnostic advice was provided in 40% of cases. The most common
      therapeutic recommendations were to de-escalate the antifungal drug (17%) or to
      suspend it (7%). Annual total antifungal expenditure was reduced from US$3.8
      million to US$2.9 million over the first 2 years, generating net savings of
      US$407,663 and US$824,458 per year after considering the cost of additional staff
      required. The ITS analyses showed a significant economic impact after the first
      12 months of the intervention (p 0.042 at month 13), which was enhanced in the
      following 24 months (p 0.006 at month 35). The number of defined daily doses
      decreased from 66.4 to 54.8 per 1000 patient-days. Incidence of candidaemia was
      reduced from 1.49 to 1.14 (p 0.08) and related mortality was reduced from 28% to
      16% (p 0.1). A collaborative and non-compulsory AFS program based on bedside
      intervention is an efficacious and cost-effective approach that optimizes the use
      of AF drugs. 

PMID- 25748496
TI  - [European Union Network for Patient Safety and Quality of Care (PASQ).
      Development and preliminary results in Europe and in the Spanish National Health
      System].
AB  - BACKGROUND: The joint action, European Union Network for Patient Safety and
      Quality of Care: PaSQ, aims to promote patient safety (PS) in the European Union
      (EU) and to facilitate the exchange of experiences among Member States (MS) and
      stakeholders on issues related to quality of care, PS, and patient involvement.
      The development and preliminary results are presented here, especially as regards
      the Spanish National Health System (SNHS). DEVELOPMENT AND METHODOLOGY: PaSQ is
      developed through 7 work packages, primarily aimed at sharing good practices
      (GP), which were identified using specific questionnaires and selected by means
      of explicit criteria, as well as to implement safe clinical practices (SCP) of
      proven effectiveness and agreed among MS. EVOLUTION OF THE JOINT ACTION: A total
      of 482 GP (39% provided by Spanish professionals) were identified. The 34 events
      organised in the EU, 11 including Spanish participation, facilitate sharing these
      practices. A total of 194 Health Care centres (49% in Spain) are implementing SCP
      (hand hygiene, safe surgery, medication reconciliation, and paediatric early
      warning scores) ACHIEVEMENTS AND FUTURE PERSPECTIVES: PaSQ is making it possible
      to strengthen collaboration between organizations and professionals at EU and
      SNHS level regarding PS and quality of care.

PMID- 25748497
TI  - [Results of implementing a programme to improve the quality of the contents in
      hospital discharge reports in cases of heart failure].
AB  - OBJECTIVES: To analyse the information collected in hospital discharge reports
      (HDR) that are given to patients with a diagnosis of heart failure (HF), and
      demonstrate the improvement in the content of these reports after the
      introduction of an intervention. MATERIAL AND METHODS: HDR with HF as the main
      diagnosis issued by the Department of Internal Medicine were analysed, and the
      presence of the diagnosis, prognosis and therapeutic data in these HDR was
      compared in a sample before and after the intervention, which consisted of
      reporting the results of analysis of the initial sample to the physicians.
      RESULTS: A total of 651 HDR (371 pre-intervention and 280 post-intervention) were
      analysed. Most of the HDR (over 70%) did not include the functional class. Most
      of the HDR did not include information about echocardiogram performed before the
      hospitalization period analysed, and most of the HDR that collected this
      information did not determine if the HF was diastolic or systolic. In the post
      intervention sample there was a lower percentage of HDR that prescribed
      angiotensin-converting enzyme inhibitors or angiotensin receptor blocker ii (26%
      vs 32%, P<.001). In 30% of the pre-intervention sample and 38% of the post
      intervention sample there was indication of beta-blockers (P=.027). CONCLUSIONS:
      A short discussion with the physicians responsible for patients with HF improves
      the inclusion of important data on the diagnosis, prognosis and treatment in the
      HDR.

PMID- 25748498
TI  - [Satisfaction with primary care nursing: use of measurement tools and explanatory
      factors].
AB  - OBJECTIVES: This study aims to assess the psychometric properties of two
      measurement tools for patient satisfaction with nursing care in Primary Care, the
      satisfaction level, and the personal and consultation characteristics associated
      with its variability. METHODS: Subjects randomly selected in 23 Health Care
      centres in the Community of Madrid were included. Satisfaction was measured by
      means of the AMABLE and Baker questionnaires, in which the psychometric
      properties were evaluated. Sociodemographic characteristics of the consultations,
      variables related to health status, and other related to the consultation process
      were collected. An explanatory model using Generalized Estimating Equations was
      constructed. RESULTS: The 662 subjects expressed a mean satisfaction of 4.95/5
      (SD .25) with AMABLE, and 4.83/5 (SD .42) with the Baker questionnaire. AMABLE
      had a single dimension (Cronbach's alpha .85), and Baker three: professional care
      (mean 4.76, SD .48 Cronbach's alpha .74), depth of relationship (mean 3.76, SD
      1.18, Cronbach's alpha .73), and perceived time (mean 4.42, SD .86, Cronbach's
      alpha .47). Ageing, a better perception of health status, and appointments
      arranged by nurses were associated with higher expressed satisfaction. Home care,
      hospital admissions, delayed consultation, extended family, or high family income
      were associated with lower satisfaction. CONCLUSIONS: Satisfaction with nurse
      consultations in Primary Care was very high, and varied depending on personal
      characteristics and on the type of consultation. The assessed tools allowed this
      outcome to be measured properly.

PMID- 25748499
TI  - Apelin protects against acute renal injury by inhibiting TGF-beta1.
AB  - Renal ischemia/reperfusion (I/R) injury is the most common cause of acute kidney
      injury, having a high rate of mortality and no effective therapy currently
      available. Apelin-13, a bioactive peptide, has been shown to inhibit the early
      lesions of diabetic nephropathy in several mouse models by us and others. To test
      whether apelin-13 protects against renal I/R induced injury, male rats were
      exposed to renal I/R injury with or without apelin-13 treatment for 3 days.
      Apelin-13 treatment markedly reduced the injury-induced tubular lesions, renal
      cell apoptosis, and normalized the injury induced renal dysfunction. Apelin-13
      treatment inhibited the injury-induced elevation of inflammatory factors and Tgf
      beta1, as well as apoptosis. Apelin-13 treatment also inhibited the injury
      induced elevation of histone methylation and Kmt2d, a histone methyltransferase
      of H3K4me2, following renal I/R injury. Furthermore, in cultured renal mesangial
      and tubular cells, apelin-13 suppressed the injury-induced elevation of Tgf
      beta1, apoptosis, H3K4me2 and Kmt2d under the in vitro hypoxia/reperfusion (H/R)
      conditions. Consistently, over-expression of apelin significantly inhibited H/R
      induced elevation of TGF-beta1, apoptosis, H3K4me2 and Kmt2d. The present study
      therefore suggests apelin-13 may be a therapeutic candidate for treating acute
      kidney injury.

PMID- 25748500
TI  - Safety of sports facilities and training of graduates in physical education.
AB  - INTRODUCTION: Post-industrial societies have to face the problem of physical
      inactivity and inappropriate lifestyles. Programs to promote physical activity
      are strongly supported by supranational, national and local institutions and
      organizations. These programs can be developed in sport facilities but also in
      places that are not institutionally dedicated to sport. The use of urban and
      working sites has the advantage of better reach the various segments of the
      population, but at the same time requires coordination between various
      professionals in structuring an effective intervention. METHODS: Bibliographical
      research in the historical archives of the library of the University of Rome Foro
      Italico, online databases, paleoigiene (wikigiene), documents archives (GSMS
      SItI, WHO, ISS, OsEPi, INAIL, ISTAT, national laws). RESULTS AND CONCLUSION:
      Several guidelines and regulations face the problem of safety in sport
      environments. The context is in rapid evolution and directions are provided by
      public health authorities. Graduates in Sport and Physical Activity, represent an
      additional resource in terms of: prevention and safety in the workplace, health
      education, application of preventive and adapted physical activities in the
      territory. These tasks can be integrated in all prevention stages: e.g. childhood
      and primary prevention programs in school, adapted physical activity for the
      elderly. The contribution of public health specialists is strategic in the
      surveillance and coordination of integrated projects. At the same time, graduates
      in Physical Education appear to be pivots for health promotion and qualified
      resources for institutions in the territory. Their training should always include
      contents related to prevention and safety, regulations on sport and working
      environments, along with bases of preventive medicine related to the context of
      physical activity.

PMID- 25748501
TI  - The role of the hygienist in prevention and health promotion through physical
      activity: the contribute of the Working Group "Movement Sciences for Health" of
      the Italian Society of Hygiene.
AB  - Inactivity is the fourth leading risk factor for chronic diseases morbidity and
      mortality, with high related costs. Exercise represents a useful instrument of
      preventive medicine due to its effects in maintaining and improving psycho
      physical wellbeing at any age and condition. The promotion of physical activity
      may represent an important prevention strategy for public health, and it implies
      an interaction among several figures from health and wellbeing settings. Due to
      their competencies in prevention and health promotion, hygienists play a
      fundamental role as intermediary among the different actors involved in this
      multidisciplinary scenario. The Working Group "Movement Sciences for Health" of
      the Italian Society of Hygiene, established in 2009, is engaged in detailing,
      evaluating and strengthening the role of physical activity for health promotion.
      It combines rigorous research activities regarding human movement for health with
      their application in public health setting and with the evaluation of their
      sustainability. Its attention is also focused on the safety aspects related to
      structural conditions of sport facilities and to health conditions or behaviours
      of their users as well. These activities led to numerous scientific publications
      and training events. 

PMID- 25748502
TI  - Ballet and stress. A pilot study.
AB  - BACKGROUND: Work-related stress is a complex problem requiring a work environment
      based assessment. Artists like dancers represent a category of atypical workers
      potentially at high risk for work-related stress. Aim of our pilot study is to
      evaluate organizational stress in a population of professional dancers, using the
      HSE Indicator Tool for Work Related Stress. METHODS: We administered the Italian
      version of the HSE Indicator Tool to 38 ballet dancers, males and females. The
      questionnaire evaluates 7 key organizational dimensions: demand, control,
      managers' support, peer support, relationships, role and change. RESULTS: The
      standards required-ideal conditions are achieved in none of the above-mentioned
      dimensions. Change is the only dimension for which results fall between the 20th
      and the 50th percentile, while for other dimensions results fall below the 20th
      percentile suggesting the need for immediate corrective action. In male dancers
      an acceptable situation is highlighted for the dimension "change" compared to
      female dancers. In both sexes there is a high frequency of subjects complaining
      of verbal abuse, bullying and harassment. CONCLUSIONS: Despite the small sample
      size, our pilot study highlights the presence of heightened levels of
      organizational stress. Preventive measures targeted towards improving
      communication between managers and dancers and aimed at team building should be
      implemented.

PMID- 25748503
TI  - Environmental health risk communication in the case "Terra dei Fuochi": content
      analysis of online newspaper articles.
AB  - BACKGROUND: The aim of the study is to evaluate the way in which information is
      conveyed by one of the major national newspapers, in its online version,
      Repubblica.it, about health risks associated with the "Terra dei Fuochi".
      METHODS: A retrospective systematic search in the online newspaper database was
      carried out for articles published from 1st January through 13th May 2014. The
      keyword used was "Terra dei Fuochi". A corpus, containing all articles included,
      was built in order to perform content analysis and text-mining using the T-LAB
      software, together with a critical interpretation. The co-occurrence analysis was
      performed using the keywords: environment, prevention, waste , risk and science.
      RESULTS: A total of 211 articles were retrieved, but only 188 articles met the
      inclusion criteria and were included in the analysis. The section of publication
      with the largest number of articles was represented by Repubblica Napoli edition
      with 50% of articles, whereas, only 2% of articles were included in the
      Environment section, and no article has been placed in the Health section. The
      most occurring lemmas were: waste, Naples, President, environmental - environment
      and health. Lemmas as disaster, drama, alarm and fear occur with medium
      frequency. Among the lemmas with less occurrence there were: remediation, cancer,
      people, information and recycle. However, terms as communication and risk
      management were absent. CONCLUSIONS: This study contributes to our understanding
      of how environmental health risks associated with the "Terra dei Fuochi" issue
      are presented by the newspapers to the public, which has implications for how the
      public may learn about risk management information.

PMID- 25748504
TI  - Assessing human exposure to inorganic arsenic in high-arsenic areas of Latium: a
      biomonitoring study integrated with indicators of dietary intake.
AB  - BACKGROUND: In Latium (central Italy), arsenic concentrations exceeding the
      regulatory limit of 10 MUg/L for drinking water are present in groundwater from a
      large area of volcanic origin. At least in part of the area, high arsenic
      concentrations have been detected also in soil and phytoavailable geogenic
      arsenic enters the food chain. As a result, local population may be exposed to
      inorganic arsenic via water and also through consumption of food with higher than
      background arsenic concentrations. METHODS: A cross sectional study was conducted
      to assess inorganic arsenic exposure and metabolism in 269 residents of 27
      municipalities in the provinces of Viterbo, Rome and Latina. Total arsenic in
      toenails and the sum of inorganic arsenic and methylated metabolites in urine,
      the latter determined by HPLC-ICP-MS, were used as biomarkers of inorganic
      arsenic exposure. All the subjects involved in the study provided samples of the
      water(s) used for drinking and cooking as well as detailed information on water
      use. To get an insight into dietary intake from locally-processed food, inorganic
      arsenic in bread samples collected in affected municipalities of the three
      provinces was determined and compared to background levels of samples from
      reference areas. RESULTS: 30% of the sample used bottled water or resorted to
      water treatment in order to lower the arsenic content <10 MUg/L (Group 1), 51% of
      the sample drank bottled water and used tap water with an arsenic content
      exceeding 10 MUg/L for cooking only (Group 2), 19% of the sample used tap water
      with an arsenic content exceeding 10 MUg/L for both drinking and cooking (Group
      3). Nail arsenic was higher for Group 2 and 3 compared to Group 1, whereas all
      groups had higher nail arsenic than the reference group. The sum of inorganic
      arsenic and related metabolites in urine was higher in Group 3 than in the other
      two groups, and higher in Group 2 compared to Group 1. White bread from the study
      area showed significantly higher inorganic arsenic levels compared to samples
      from reference areas. CONCLUSIONS: Use of toenail arsenic as biomarker of long
      term exposure allowed to retrospectively reconstruct exposure irrespective of
      recent modifications due to changes in water use. In Group 3, urinary
      concentration of inorganic arsenic and metabolites exceeded the upper limit of
      the reference concentration range for the Italian population. Inter-individual
      variability of the efficiency of arsenic metabolism in the study population was
      substantial indicating that a subgroup of the population is more susceptible to
      the toxic effects of inorganic arsenic owing to a lower methylation capability.

PMID- 25748505
TI  - Factors influencing groundwater quality: towards an integrated management
      approach.
AB  - The safety of groundwater resources is a serious issue, particularly when these
      resources are the main source of water for drinking, irrigation and industrial
      use in coastal areas. In Italy, 85% of the water used by the public is of
      underground origin. The aim of this report is to analyze the main factors that
      make groundwater vulnerable. Soil characteristics and filtration capacity can
      promote or hinder the diffusion of environmental contaminants. Global climate
      change influences the prevalence and degree of groundwater contamination.
      Anthropic pressure causes considerable exploitation of water resources, leading
      to reduced water availability and the progressive deterioration of water quality.
      Management of water quality will require a multidisciplinary, dynamic and
      practical approach focused on identifying the measures necessary to reduce
      contamination and mitigate the risks associated with the use of contaminated
      water resources. 

PMID- 25748506
TI  - Mineral water or tap water? An endless debate.
AB  - The consumption of mineral water has been increasing because of the frequent and
      unjustified reports of the water supply contamination. However some authors have
      shown that bottled waters are not always better than tap water. Mineral waters
      are more palatable for organoleptic characteristic because, being pure at source,
      they do not undergo disinfection treatments and are sometimes enriched with CO2.
      In fact, they are characterized by their microbial facies subject to changes
      during the production cycle which can contribute to their contamination. It is
      necessary to provide people with the tools necessary to operate a critical choice
      of the type of water to be consumed not exclusively for their organoleptic
      characteristics or marketing strategies. 

PMID- 25748507
TI  - Research priorities in Italian diabetes nursing care: findings from a Delphi
      study.
AB  - AIM: Defining a set of research priorities for diabetes nursing care in the
      Italian context. DESIGN: A two-step study design based on a modified Delphi
      technique was undertaken in 2013. METHODS: In the first stage of research, five
      systematic reviews of literature were performed. Among them 865 recommendations
      in diabetes nursing care emerged, and 217 (25.1%) were categorized at level IV or
      lower, thus based on a lack of knowledge and therefore a potential research area.
      Homogeneous recommendations among the 217 emerged and were categorized by two
      researchers independently: 96 final recommendations were identified and
      transformed into items embodied into a questionnaire. A Likert scale ranging from
      1 (very low) to 5 (very high) was used to collect the consensus regarding
      priority. For that purpose a sample of 200 nurses was randomly considered.
      Potential participants were invited to cooperate via email through a letter
      reporting aims and methods. In the first round 85 nurses participated; in the
      third and final round, only 13 nurses took part. RESULTS: Participants have
      identified 14 research priorities categorized into three main areas: 1) education
      strategies' effectiveness (n=7); 2) models of care delivery and advanced nursing
      education effectiveness (n=4); and 3) in specific clinical issues (n=3).
      CONCLUSIONS: More research on patient education and on models of care delivery
      and advanced nursing education should be included in any future Italian agenda.

PMID- 25748508
TI  - [Inconsistencies between building regulations in force in Italy for indoor
      environment and wellness factors].
AB  - Indoor environment is one of major health determinants, and the regulations that
      set the sanitary requirements are of primary importance for the protection of
      public health. The authors analyse the critical aspects of the complex Italian
      regulatory system, starting from the EU regulations, through national and
      regional laws, and finally the municipal regulations. They underline the need for
      more uniformity and clarity in the determination of health standards, as well as
      for a simplification of the existing legislation. Moreover, they highlight the
      importance of controlling and monitoring indoor environment, currently almost
      completely absent in Italy due to the effects of the regulatory changes of the
      latest years. 

PMID- 25748509
TI  - Ebola virus disease outbreak: what's going on.
AB  - The current West African Ebola Virus Disease (EVD) outbreak was confirmed in
      March, 2014, and after months of slow, fragmented responses, the EVD has been
      recognized as a public health emergency of international concern. The early
      diagnosis of the disease is difficult without laboratory testing, because its
      symptoms can be seen in many other infections. In the wake of international
      agencies advices, the Italian Ministry of Health, on October 1, 2014, released to
      the Healthcare Professional Workers (HPWs) the Protocol about the management of
      cases and contacts within the national territory. Due to the increasing number of
      humanitarian groups and HPWs involved in the field, the probability to have new
      cases of contamination is higher than ever. Proven specific treatments against
      EVD are not yet available, however, a variety of compounds have been under
      testing. The most effective are select monoclonal antibodies that have a high
      neutralizing potential against epitopes of Ebola Virus. For facing the matter, it
      is important a comprehensive approach according to the recommendations proposed
      by the international agencies because no single institution or country has all
      the capacities to respond to a new and emerging infectious disease. 

PMID- 25748511
TI  - Genetic variation in transmission success of the Lyme borreliosis pathogen
      Borrelia afzelii.
AB  - The vector-to-host and host-to-vector transmission steps are the two critical
      events that define the life cycle of any vector-borne pathogen. We expect
      negative genetic correlations between these two transmission phenotypes, if
      parasite genotypes specialized at invading the vector are less effective at
      infecting the vertebrate host and vice versa. We used the tick-borne bacterium
      Borrelia afzelii, a causative agent of Lyme borreliosis in Europe, to test
      whether genetic trade-offs exist between tick-to-host, systemic (host-to-tick),
      and a third mode of co-feeding (tick-to-tick) transmission. We worked with six
      strains of B. afzelii that were differentiated according to their ospC gene. We
      compared the three components of transmission among the B. afzelii strains using
      laboratory rodents as the vertebrate host and a laboratory colony of Ixodes
      ricinus as the tick vector. We used next generation matrix models to combine
      these transmission components into a single estimate of the reproductive number
      (R0) for each B. afzelii strain. We also tested whether these strain-specific
      estimates of R0 were correlated with the strain-specific frequencies in the
      field. We found significant genetic variation in the three transmission
      components among the B. afzelii strains. This is the first study to document
      genetic variation in co-feeding transmission for any tick-borne pathogen. We
      found no evidence of trade-offs as the three pairwise correlations of the
      transmission rates were all positive. The R0 values from our laboratory study
      explained 45% of the variation in the frequencies of the B. afzelii ospC strains
      in the field. Our study suggests that laboratory estimates of pathogen fitness
      can predict the distribution of pathogen strains in nature. 

PMID- 25748510
TI  - Pervasive variation of transcription factor orthologs contributes to regulatory
      network evolution.
AB  - Differences in transcriptional regulatory networks underlie much of the
      phenotypic variation observed across organisms. Changes to cis-regulatory
      elements are widely believed to be the predominant means by which regulatory
      networks evolve, yet examples of regulatory network divergence due to
      transcription factor (TF) variation have also been observed. To systematically
      ascertain the extent to which TFs contribute to regulatory divergence, we
      analyzed the evolution of the largest class of metazoan TFs, Cys2-His2 zinc
      finger (C2H2-ZF) TFs, across 12 Drosophila species spanning ~45 million years of
      evolution. Remarkably, we uncovered that a significant fraction of all C2H2-ZF 1
      to-1 orthologs in flies exhibit variations that can affect their DNA-binding
      specificities. In addition to loss and recruitment of C2H2-ZF domains, we found
      diverging DNA-contacting residues in ~44% of domains shared between D.
      melanogaster and the other fly species. These diverging DNA-contacting residues,
      found in ~70% of the D. melanogaster C2H2-ZF genes in our analysis and
      corresponding to ~26% of all annotated D. melanogaster TFs, show evidence of
      functional constraint: they tend to be conserved across phylogenetic clades and
      evolve slower than other diverging residues. These same variations were rarely
      found as polymorphisms within a population of D. melanogaster flies, indicating
      their rapid fixation. The predicted specificities of these dynamic domains
      gradually change across phylogenetic distances, suggesting stepwise evolutionary
      trajectories for TF divergence. Further, whereas proteins with conserved C2H2-ZF
      domains are enriched in developmental functions, those with varying domains
      exhibit no functional enrichments. Our work suggests that a subset of highly
      dynamic and largely unstudied TFs are a likely source of regulatory variation in
      Drosophila and other metazoans. 

PMID- 25748512
TI  - Influence of altitude on tick-borne encephalitis infection risk in the natural
      foci of the Altai Republic, Southern Siberia.
AB  - The Altai Republic is a highly endemic area as far as tick-borne encephalitis
      (TBE) is concerned. The aim of the research was to study the effect of altitude
      on the risk of tick-borne encephalitis infection in the Altai Republic. The paper
      analyzes the following data: the study of ixodid ticks collected from the
      vegetation in 116 sites at the 200-2383m elevation above sea level in 2012-2014,
      TBE virus prevalence of these vectors, tick-bite incidence rate, and TBE
      incidence rate of the population. Species identification of 4503 specimens has
      shown that the most common species are Dermacentor nuttalli (45.3%), Ixodes
      persulcatus (33.1%), Dermacentor silvarum (9.4%), Dermacentor reticulatus (8.9%),
      and Haemaphysalis concinna (5.0%). A total of 2997 adult ixodid ticks were
      studied for the presence of the TBE virus; 2163 samples were examined by ELISA,
      while 834 specimens were tested by PCR. The TBE virus prevalence of Dermacentor
      spp. ticks in both reactions was significantly higher than of Ixodes persulcatus
      ticks (p<0.001). The work shows that the altitude is an important factor in the
      development of the epidemiological situation of tick-borne encephalitis: the
      higher the elevation of the area above sea level, the smaller the range of
      vectors. There is also a change of a leading species: in middle altitude (800
      1700m above sea level) the virus is transmitted by ticks of D. nuttalli along
      with I. persulcatus, and in high mountains (above 1700m above sea level) D.
      nuttalli becomes an absolute dominant species. However, these species of ticks
      are less effective vectors than I. persulcatus. With the increase of altitude the
      tick-bite incidence rate decreases (r=-0.78, p<0.05), and TBE incidence also
      reduces (r=-0.67, p<0.05). 

PMID- 25748513
TI  - Management for squamous cell carcinoma of the nasal cavity and ethmoid sinus: A
      single institution experience.
AB  - OBJECTIVE: Here we report our experience of patients with squamous cell carcinoma
      (SCC) of the nasal cavity and ethmoid sinus (NC&ES) together with an analysis of
      treatment outcomes. METHODS: A retrospective analysis was performed using data
      from 25 consecutive patients treated between 2000 and 2012. Four patients were
      diagnosed with T1, 3 with T2, 4 with T3, 7 with T4a, and 7 with T4b disease. No
      patient had lymph node metastasis. RESULTS: Twelve patients were treated with
      surgery with/without radiotherapy and with/without chemotherapy. Of these, 4
      underwent endoscopic surgery without an open approach and 3 required an anterior
      skull base approach. Thirteen were treated with radiotherapy; 1 with radiotherapy
      alone, and 4 and 8 with intravenous and intra-arterial chemotherapy,
      respectively. The 5-yr overall survival for T1-3, T4a, and T4b disease was 53.9%,
      71.4%, and 29.0%, respectively. The 5-yr disease-specific survival for T1-3, T4a,
      and T4b disease was 74.1%, 71.4%, and 29.0%, respectively. CONCLUSION: Our
      treatment policy for patients with SCC of NC&ES, which basically follows the NCCN
      guideline, was considered to be appropriate. However, several points in terms of
      surgery and non-surgical approach remain to be solved through further research.

PMID- 25748514
TI  - Treatment of nostril and nasal stenosis due to facial burn using a self
      expandable metallic esophageal stent.
AB  - For the treatment of nasal and nostril stenosis caused by facial burn, it is
      necessary to perform rhinoplasty and nasal vestibuloplasty using various flaps,
      perform cicatrectomy of the nostrils with a rhinosurgical procedure, and prevent
      restenosis of the nostrils and nasal cavity for a certain period by methods such
      as placement of a nasal retainer or transnasal airway and gauze packing of the
      nasal cavity. With all methods, postoperative placement of a retainer or nasal
      treatment is necessary for the prevention of postoperative restenosis, and the
      patient's cooperation is essential. In a patient who did not cooperate in
      postoperative treatments due to autism and had recurrences of nasal and nostril
      stenosis after conventional surgical treatments, adequate patency of the nasal
      cavity and nostrils could be maintained with minimal postoperative treatment by
      placing a self-expandable metallic esophageal stent. 

PMID- 25748515
TI  - Laryngeal tuberculosis: A report of 17 cases.
AB  - OBJECTIVE: The aim of this study was to reduce misdiagnosis and inappropriate
      treatment of laryngeal tuberculosis. METHODS: Between April 2009 and March 2013,
      1660 inpatients with tuberculosis were treated at the Osaka Prefectural Medical
      Center for Respiratory and Allergic Diseases. Seventeen of these patients were
      diagnosed with laryngeal tuberculosis. Criteria used for diagnosis were findings
      of histologic examination of biopsy specimens (2 patients) or clinical response
      of granuloma to antituberculosis therapy (15 patients). Medical records were used
      for this retrospective study. RESULTS: Patients' age ranged from 30 to 84 years
      with an average of 51.4+/-14.0 years (mean+/-SE); nine were men and eight were
      women. The most frequent chief complaint was hoarseness (n=15). Thirteen patients
      had persistent cough before they showed otolaryngologic symptoms. Endoscopic
      findings were categorized into five types of lesions: perichondritic (n=6),
      ulcerative (n=6), granulomatous (n=6), polypoid (n=1) and nonspecific
      inflammatory (n=1). Laryngeal tuberculosis showed as a single lesion in one
      patient and as multiple lesions in the other patients. The most commonly involved
      site was the true vocal cord (n=16, 94.1%), while 16 patients showed radiographic
      evidence of active pulmonary tuberculosis. These results indicate that
      deterioration of the lesions tended to result in the occurrence of multiple
      lesions. CONCLUSION: While morbidity in tuberculosis has been decreasing in
      Japan, a significant number of patients still has laryngeal tuberculosis in
      association with advanced pulmonary tuberculosis. If a patient has a protracted
      cough, laryngeal tuberculosis should be taken into consideration for differential
      diagnosis. Pulmonary imaging study should be performed for early diagnosis and to
      prevent the infection from spreading.

PMID- 25748516
TI  - Characterization of two novel gammapapillomaviruses, HPV179 and HPV184, isolated
      from common warts of a renal-transplant recipient.
AB  - Gammapapillomavirus (Gamma-PV) is a diverse and rapidly expanding PV-genus,
      currently consisting of 76 fully characterized human papillomavirus (HPV) types.
      In this study, DNA genomes of two novel HPV types, HPV179 and HPV184, obtained
      from two distinct facial verrucae vulgares specimens of a 64 year-old renal
      transplant recipient, were fully cloned, sequenced and characterized. HPV179 and
      HPV184 genomes comprise 7,228-bp and 7,324-bp, respectively, and contain four
      early (E1, E2, E6 and E7) and two late genes (L1 and L2); the non-coding region
      is typically positioned between L1 and E6 genes. Phylogenetic analysis of the L1
      nucleotide sequence placed both novel types within the Gamma-PV genus: HPV179 was
      classified as a novel member of species Gamma-15, additionally containing HPV135
      and HPV146, while HPV184 was classified as a single member of a novel species
      Gamma-25. HPV179 and HPV184 type-specific quantitative real-time PCRs were
      further developed and used in combination with human beta-globin gene
      quantitative real-time PCR to determine the prevalence and viral load of the
      novel types in the patient's facial warts and several follow-up skin specimens,
      and in a representative collection, a total of 569 samples, of HPV-associated
      benign and malignant neoplasms, hair follicles and anal and oral mucosa specimens
      obtained from immunocompetent individuals. HPV179 and HPV184 viral loads in
      patients' facial warts were estimated to be 2,463 and 3,200 genome copies per
      single cell, respectively, suggesting their active role in the development of
      common warts in organ-transplant recipients. In addition, in this particular
      patient, both novel types had established a persistent infection of the skin for
      more than four years. Among immunocompetent individuals, HPV179 was further
      detected in low-copy numbers in a few skin specimens, indicating its cutaneous
      tissue tropism, while HPV184 was further detected in low-copy numbers in one
      mucosal and a few skin specimens, suggesting its dual tissue tropism. 

PMID- 25748517
TI  - Log-Linear Modeling of Agreement among Expert Exposure Assessors.
AB  - BACKGROUND: Evaluation of expert assessment of exposure depends, in the absence
      of a validation measurement, upon measures of agreement among the expert raters.
      Agreement is typically measured using Cohen's Kappa statistic, however, there are
      some well-known limitations to this approach. We demonstrate an alternate method
      that uses log-linear models designed to model agreement. These models contain
      parameters that distinguish between exact agreement (diagonals of agreement
      matrix) and non-exact associations (off-diagonals). In addition, they can
      incorporate covariates to examine whether agreement differs across strata.
      METHODS: We applied these models to evaluate agreement among expert ratings of
      exposure to sensitizers (none, likely, high) in a study of occupational asthma.
      RESULTS: Traditional analyses using weighted kappa suggested potential
      differences in agreement by blue/white collar jobs and office/non-office jobs,
      but not case/control status. However, the evaluation of the covariates and their
      interaction terms in log-linear models found no differences in agreement with
      these covariates and provided evidence that the differences observed using kappa
      were the result of marginal differences in the distribution of ratings rather
      than differences in agreement. Differences in agreement were predicted across the
      exposure scale, with the likely moderately exposed category more difficult for
      the experts to differentiate from the highly exposed category than from the
      unexposed category. CONCLUSIONS: The log-linear models provided valuable
      information about patterns of agreement and the structure of the data that were
      not revealed in analyses using kappa. The models' lack of dependence on marginal
      distributions and the ease of evaluating covariates allow reliable detection of
      observational bias in exposure data.

PMID- 25748518
TI  - Amino Acid Degradations Produced by Lipid Oxidation Products.
AB  - Differently to amino acid degradations produced by carbohydrate-derived reactive
      carbonyls, amino acid degradations produced by lipid oxidation products are
      lesser known in spite of being lipid oxidation a major source of reactive
      carbonyls in food. This article analyzes the conversion of amino acids into
      Strecker aldehydes, alpha-keto acids, and amines produced by lipid-derived free
      radicals and carbonyl compounds, as well as the role of lipid oxidation products
      on the reactions suffered by these compounds: the formation of Strecker aldehydes
      and other aldehydes from alpha-keto acids; the formation of Strecker aldehydes
      and olefins from amines; the formation of shorter aldehydes from Strecker
      aldehydes; and the addition reactions suffered by the olefins produced from the
      amines. The relationships among all these reactions and the effect of reaction
      conditions on them are discussed. This knowledge should contribute to better
      control food processing in order to favor the formation of desirable beneficial
      compounds and to inhibit the production of compounds with deleterious properties.

PMID- 25748519
TI  - Discovering less toxic ionic liquids by using the Microtox(r) toxicity test.
AB  - New Microtox(r) toxicity data of 16 ionic liquids of different cationic and
      anionic composition were determined. The ionic liquids 1-butyl-1
      methylpyrrolidinium trifluoromethanesulfonate, [BMPyr(+)][TFO(-)], 1-butyl-1
      methylpyrrolidinium chloride, [BMPyr(+)][Cl(-)], hydroxypropylmethylimidazolium
      fluoroacetate, [HOPMIM(+)][FCH2COO(-)], and hydroxypropylmethylimidazolium
      glycolate [HOPMIM(+)][glycolate(-)] were found to be less toxic than conventional
      organic solvent such as chloroform or toluene, accoding the Microtox(r) toxicity
      assays. The toxicity of pyrrolidinium cation was lower than the imidazolium and
      pyridinium ones. It was found that the inclusion of an hydroxyl group in the
      alkyl chain length of the cation also reduce the toxicity of the ionic liquid. To
      sum up, the Microtox(r) toxicity assays can be used as screening tool to easily
      determined the toxicity of a wide range of ionic liquids and the toxicity data
      obtained could allow the obtention of structure-toxicity relationships to design
      less toxic ionic liquids. 

PMID- 25748520
TI  - Fulminant amoebic colitis: a clinicopathological study of 30 cases.
AB  - AIMS: To review the clinical and pathological factors associated with fulminant
      amoebic colitis (FAC) requiring colonic resection and its outcome. METHODS: We
      retrospectively identified adult patients admitted to our centre between June
      2007 and December 2011 with FAC who underwent colonic resection and were
      diagnosed with amoebic colitis based on the presence of trophozoites on
      histological examination. The clinical details were extracted from the medical
      notes and correlated with the pathological findings. RESULTS: Thirty patients (18
      men and 12 women) met the inclusion criteria. Their mean age was 50.1 years
      (range 21-89). The most frequent symptoms were abdominal pain, vomiting and
      fever. More than half the patients (16/30) had underlying conditions associated
      with immunosuppression including diabetes mellitus and tuberculosis. Pathological
      investigation of colonic resections showed predominantly right-sided involvement
      with geographic colonic ulcers covered with a creamy-white pseudomembrane,
      perforations, gangrenous changes, amoeboma and lesions mimicking inflammatory
      bowel disease. All showed basophilic dirty necrosis with abundant nuclear debris
      and amoebic trophozoites on histological examination. 21/30 patients (70%) had
      involvement beyond the caecum. 17/30 patients (57%) died. Those with involvement
      beyond the caecum were more likely to die (15/21, 71.4%) than those with less
      extensive disease. CONCLUSIONS: FAC presents as acute abdomen and can mimic
      appendicitis, ischaemic bowel disease, tuberculosis and malignancy. Comorbidities
      causing immunosuppression frequently associated. Mortality remains high despite
      surgery, so FAC should be suspected in every case of acute abdomen with colonic
      perforation if associated with typical gross and microscopic findings and a
      history of stay in an endemic area.

PMID- 25748521
TI  - Photoacoustic spectrum analysis for microstructure characterization in biological
      tissue: analytical model.
AB  - Photoacoustic spectrum (PA) analysis (PASA) has been found to have the ability to
      identify the microstructures in phantoms and biological tissues. PASA adopts the
      procedures in ultrasound spectrum analysis, although the signal generation
      mechanisms related to ultrasound backscatter and PA wave generation differ. The
      purpose of this study was to theoretically validate PASA. The analytical solution
      to the power spectrum of PA signals generated by identical microspheres following
      discrete uniform random distribution in space was derived. The simulation and
      experiment validation of the analytical solution include: (i) the power spectrum
      profile of a single microsphere with a diameter of 300 MUm, and (ii) the PASA
      parameters of the PA signals generated by randomly distributed microspheres 100,
      200, 300, 400 and 500 MUm in diameter, at concentrations of 30, 60, 120, 240, 480
      per 1.5(3) cm(3) in the observation range 0.5-13 MHz.

PMID- 25748522
TI  - Role of 3-D ultrasound in clinical obstetric practice: evolution over 20 years.
AB  - The use of 3-D ultrasound in obstetrics has undergone dramatic development over
      the past 20 years. Since the first publications on this application in clinical
      practice, several 3-D ultrasound techniques and rendering modes have been
      proposed and applied to the study of fetal brain, face and cardiac anatomy. In
      addition, 3-D ultrasound has improved calculations of the volume of fetal organs
      and limbs and estimations of fetal birth weight. And furthermore, angiographic
      patterns of fetal organs and the placenta have been assessed using 3-D power
      Doppler ultrasound quantification. In this review, we aim to summarize current
      evidence on the clinical relevance of these methodologies and their application
      in obstetric practice.

PMID- 25748523
TI  - Comparison of three methods for the confirmation of laryngeal mask airway
      placement in female patients undergoing gynecologic surgery.
AB  - The laryngeal mask airway (LMA) is a supraglottic device that is commonly used to
      provide lung ventilation during general anesthesia. LMA placement needs to be
      confirmed to provide adequate lung ventilation. To investigate the feasibility of
      using ultrasound examination, compared with clinical tests and fiberoptic
      laryngoscopy, to confirm LMA placement, we performed a clinical study of 64
      female patients classified as American Society of Anesthesiologists Physical
      Status I or II who were scheduled for gynecologic surgery with LMA insertion for
      airway management. After insertion, placement of the LMA was confirmed by
      clinical tests, ultrasound examination and fiberoptic laryngoscopy. Of the 64
      women, placement was confirmed as acceptable in 89.1% by clinical tests, in 59.4%
      by fiberoptic laryngoscope assessment and in 67.2% by ultrasound examination.
      With respect to patients with oropharyngeal leaks classified as high, there were
      no differences in confirmation of acceptable placement between clinical tests and
      ultrasound examinations (p = 0.092), but the number of patients determined to
      have acceptable placement by ultrasound examination was greater than that
      determined by fiberoptic laryngoscopy (p = 0.034). Thus, ultrasound examination
      is a superior technique for confirming the seal on the LMA.

PMID- 25748524
TI  - Reply to the Letter to the editor regarding Do not forget to calculate the mean
      shear wave speed as assessed by acoustic radiation force impulse elastography as
      a harmonic mean, not an arithmetical mean.

PMID- 25748525
TI  - Reliability and agreement of ultrasonographic thickness measurements of the
      common lateral extensors of the elbow.
AB  - In individuals with lateral elbow tendinopathy, the thickness of the common
      lateral extensors tendon can be evaluated by musculoskeletal ultrasonography
      (MSU) for diagnostic and evaluative purposes. The reproducibility of these
      thickness measurements should be established before integrating it into daily
      practice. A test-retest design was used to determine the reproducibility of these
      measurements in the longitudinal and transverse planes. Seventy-three healthy
      participants were measured two times by two raters. Intra-class correlation
      coefficient values for inter-rater reliability for the longitudinal and
      transverse planes were 0.67 and 0.49. Intra-class correlation coefficient values
      for intra-rater reliability varied between 0.73 and 0.92. The smallest detectable
      change ranged from 0.50 to 0.78 mm and comprised 9.8%-16.3% of the mean
      thickness. MSU thickness measurement of the common lateral extensors tendon of
      the elbow has fair to excellent intra- and inter-rater reliability. Additionally,
      agreement is acceptable, which makes MSU a valuable tool for the evaluation of
      tendon thickness over time. 

PMID- 25748526
TI  - Total urogenital mobilization by CAH: a step-by-step illustration of the
      technique.
AB  - INTRODUCTION: Congenital adrenal hyperplasia (CAH) resulting from deficient 21
      hydroxylase activity is an autosomal recessive disorder with an incidence of
      1:5000-25,000 in Caucasian populations. Despite various techniques to treat CAH,
      total urogenital mobilization (TUM) has gained popularity. This technique has low
      morbidity, and can be performed by the perineal route with the patient in the
      dorsal lithotomy position without the need to separate the urethra from the
      vagina. We aim to demonstrate in this video the TUM technique step by step.
      METHODS: A 9-month-old child, born with ambiguous genitalia (Prader 3) with a
      46XX karyotype and CAH diagnosis presented to our facility. Endoscopy showed a 2
      cm common channel. RESULTS AND DISCUSSION: The patient was treated as described
      in the video and she had an uneventful clinical outcome with complete healing.
      TUM is an excellent alternative for treating CAH.

PMID- 25748527
TI  - Complete female epispadia: the case for perineal approach.
AB  - INTRODUCTION: Complete female epispadia (CFE) is a rare congenital anomaly
      occurring in 1 of 500,000 live births. The goals of CFE management include
      achieving continence, while protecting the kidneys, and creating functional,
      cosmetic external genitalia. PATIENT AND METHODS: We demonstrate in this video
      the steps of the surgery and present midterm follow-up of a 6-year-old child with
      CFE. RESULTS AND DISCUSSION: The patient had an excellent cosmetic result, and
      reported continence of 3 h period with mild leakage. The perineal infrapubic
      approach offers the possibility of restoring cosmesis and providing resistance in
      one surgery precluding the need for abdominal bladder neck surgery.

PMID- 25748528
TI  - Intermolecular reductive coupling of esters with benzophenones by low-valent
      titanium: synthesis of diarylmethyl ketones revisited.
AB  - The reductive coupling of aliphatic esters with benzophenones by Zn-TiCl4 in THF
      gave two- and four-electron reduced products, diaryl(hydroxy)methyl ketones, and
      diarylmethyl ketones selectively by controlling the reaction conditions. In the
      reaction of aromatic esters with benzophenones, diarylmethyl ketones were
      obtained as the sole products. N-(Alkoxycarbonyl)-(S)-alpha-amino acid methyl
      esters gave optically active diphenylmethyl ketones by reduction with
      benzophenone. The obtained diphenylmethyl ketones were transformed to 4,5-cis
      disubstituted oxazolidin-2-ones stereoselectively. 

PMID- 25748529
TI  - Improvement in muscle strength after an anterior cruciate ligament injury
      corresponds with a decrease in serum cytokines.
AB  - The purpose of this communication was to identify if a decrease in serum cytokine
      concentrations associates with an improvement in muscle strength after an
      anterior cruciate ligament (ACL) injury. To establish groups with contrasting
      serum cytokine concentrations, subjects scheduled for ACL reconstructive surgery
      were separated into one of two groups (gender matched) based on their time from
      injury occurrence: (1) Early (<21-d from injury occurrence; n=22) or (2) Late
      (?21-d from injury occurrence; n=22). Before surgery, each subject provided a
      fasting blood sample and performed single-leg peak isometric force testing on the
      injured (INJ) and non-injured (NI) limbs. Compared to the NI limb, peak isometric
      force in the INJ limb was decreased (p<0.05) in both groups (Early, ~35%; Late,
      ~18%). The deficit in peak isometric force, however, was increased (p<0.05) in
      the Early compared to Late group. Similarly, serum granulocyte macrophage colony
      stimulating factor (GM-CSF), interleukin (IL)-6, and IL-13 were increased (all
      p<0.05) in the Early group. These unique findings show a concurrent increase in
      muscular weakness and serum cytokine concentrations shortly after (<21-d) an ACL
      injury. Importantly, muscular weakness persisted thereafter (?21-d) but at an
      attenuated level and parallel to a decrease in circulating cytokine
      concentrations. We conclude that a decrease in serum cytokines associates with a
      reduction in muscular weakness after an ACL injury.

PMID- 25748530
TI  - 5-HT receptor-mediated modulation of granule cell inhibition after juvenile
      stress recovers after a second exposure to adult stress.
AB  - Aversive experiences in early life are thought to dispose to psychopathologies
      such as mood or anxiety disorders. In a two-hit stress model, we assessed the
      effects of juvenile and/or adult stress on the 5-HT-mediated modulation of
      synaptic inhibition of ventral dentate gyrus granule cells. Combined but not
      single stress exposure led to a significant reduction in activity and increased
      anxiety-like behavior. Similarly, the 5-HT1A receptor-mediated inhibition of
      evoked inhibitory postsynaptic currents (IPSCs) of granule cells was only reduced
      in single stress exposed animals. This was also true for the number of granule
      cells responding with a 5-HT3 receptor-dependent burst of miniature IPSCs. 5-HT3
      receptors are expressed on cholecystokinin (CCK)+ basket cells in the
      hippocampus. In fact, we observed a reduction of steady-state mRNA levels of CCK+
      basket cell markers after single juvenile or adult stress and partial recovery
      after combined stress, thus matching the electrophysiological findings. Adaptive
      changes in 5-HT-mediated modulation of synaptic inhibition and CCK+ basket cells
      in the DG may help to maintain normal levels of anxiety after single juvenile or
      adult stress exposure, as indicated by the increased anxiety that accompanies the
      loss of this regulation upon combined stress. 

PMID- 25748531
TI  - Direct solvothermal phosphorization of nickel foam to fabricate integrated Ni2P
      nanorods/Ni electrodes for efficient electrocatalytic hydrogen evolution.
AB  - We report an easy one-step approach for fabricating integrated Ni2P-nanorods/Ni
      (Ni2P-NRs/Ni) electrodes by direct phosphorization of a commercially available
      nickel foam current collector under solvothermal conditions. The resulting self
      supported Ni2P-NRs/Ni composite electrode exhibits high electrochemical
      performance towards hydrogen evolution reaction in acidic medium. 

PMID- 25748533
TI  - Need of voriconazole high dosages, with documented cerebrospinal fluid
      penetration, for treatment of cerebral aspergillosis in a 6-month-old leukaemic
      girl.
AB  - This case report indicates the usefulness of voriconazole for the treatment of
      central nervous system (CNS) aspergillosis, also in paediatrics. However, it also
      confirms the need for therapeutic drug monitoring (TDM), especially in younger
      children that may require very high dosages in order to achieve plasma and
      cerebrospinal fluid (CSF) therapeutic concentrations.

PMID- 25748532
TI  - Human iPSC-based cardiac microphysiological system for drug screening
      applications.
AB  - Drug discovery and development are hampered by high failure rates attributed to
      the reliance on non-human animal models employed during safety and efficacy
      testing. A fundamental problem in this inefficient process is that non-human
      animal models cannot adequately represent human biology. Thus, there is an urgent
      need for high-content in vitro systems that can better predict drug-induced
      toxicity. Systems that predict cardiotoxicity are of uppermost significance, as
      approximately one third of safety-based pharmaceutical withdrawals are due to
      cardiotoxicty. Here, we present a cardiac microphysiological system (MPS) with
      the attributes required for an ideal in vitro system to predict cardiotoxicity:
      i) cells with a human genetic background; ii) physiologically relevant tissue
      structure (e.g. aligned cells); iii) computationally predictable perfusion
      mimicking human vasculature; and, iv) multiple modes of analysis (e.g.
      biological, electrophysiological, and physiological). Our MPS is able to keep
      human induced pluripotent stem cell derived cardiac tissue viable and functional
      over multiple weeks. Pharmacological studies using the cardiac MPS show half
      maximal inhibitory/effective concentration values (IC50/EC50) that are more
      consistent with the data on tissue scale references compared to cellular scale
      studies. We anticipate the widespread adoption of MPSs for drug screening and
      disease modeling.

PMID- 25748534
TI  - A semi-supervised learning approach for RNA secondary structure prediction.
AB  - RNA secondary structure prediction is a key technology in RNA bioinformatics.
      Most algorithms for RNA secondary structure prediction use probabilistic models,
      in which the model parameters are trained with reliable RNA secondary structures.
      Because of the difficulty of determining RNA secondary structures by experimental
      procedures, such as NMR or X-ray crystal structural analyses, there are still
      many RNA sequences that could be useful for training whose secondary structures
      have not been experimentally determined. In this paper, we introduce a novel semi
      supervised learning approach for training parameters in a probabilistic model of
      RNA secondary structures in which we employ not only RNA sequences with annotated
      secondary structures but also ones with unknown secondary structures. Our model
      is based on a hybrid of generative (stochastic context-free grammars) and
      discriminative models (conditional random fields) that has been successfully
      applied to natural language processing. Computational experiments indicate that
      the accuracy of secondary structure prediction is improved by incorporating RNA
      sequences with unknown secondary structures into training. To our knowledge, this
      is the first study of a semi-supervised learning approach for RNA secondary
      structure prediction. This technique will be useful when the number of reliable
      structures is limited. 

PMID- 25748535
TI  - A new vision of evaluating gene expression signatures.
AB  - Gene expression profiles based on high-throughput technologies contribute to
      molecular classifications of different cell lines and consequently to clinical
      diagnostic tests for cancer types and other diseases. Statistical techniques and
      dimension reduction methods have been devised for identifying minimal gene subset
      with maximal discriminative power. For sets of in silico candidate genes,
      assuming a unique gene signature or performing a parsimonious signature
      evaluation seems to be too restrictive in the context of in vitro signature
      validation. This is mainly due to the high complexity of largely correlated
      expression measurements and the existence of various oncogenic pathways.
      Consequently, it might be more advantageous to identify and evaluate multiple
      gene signatures with a similar good predictive power, which are referred to as
      near-optimal signatures, to be made available for biological validation. For this
      purpose we propose the bead-chain-plot approach originating from swarm
      intelligence techniques, and a small scale computational experiment is conducted
      in order to convey our vision. We simulate the acquisition of candidate genes by
      using a small pool of differentially expressed genes derived from microarray
      based CNS tumour data. The application of the bead-chain-plot provides
      experimental evidence for improved classifications by using near-optimal
      signatures in validation procedures. 

PMID- 25748536
TI  - Identification of transformation products of pesticides and veterinary drugs in
      food and related matrices: use of retrospective analysis.
AB  - Retrospective analysis has been applied in different samples, including honey,
      meat, feed and nutraceutical products from ginkgo biloba, soya, royal jelly and
      green tea, with the aim of searching transformation products of pesticides and
      veterinary drugs, which were not included in an initial analysis. Generic
      extraction and analytical procedures based on high resolution mass spectrometry
      (Exactive-Orbitrap analyser was used) have been applied. All obtained data have
      been reprocessed and some compounds as anhydroerythromycin in honey and 3,5,6
      trichloro-2-pyridinol in feed have been detected, demonstrating the applicability
      and the utility of the procedure. Advantages and disadvantages of retrospective
      approach have been highlighted. 

PMID- 25748537
TI  - Twin-column CaptureSMB: a novel cyclic process for protein A affinity
      chromatography.
AB  - A twin-column counter-current chromatography processes, CaptureSMB, was used for
      the protein A affinity capture of a monoclonal antibody (mAb). By means of
      sequential loading, the process improves the utilization of the stationary phase
      by achieving loadings much closer to the static binding capacity of the resin in
      comparison to batch chromatography. Using a mAb capture case study with protein A
      affinity chromatography, the performance and product quality obtained from
      CaptureSMB and batch processes were compared. The effect of the flow rate, column
      length and titer concentration on the process performance and product quality
      were evaluated. CaptureSMB showed superior performance compared to batch
      chromatography with respect to productivity, capacity utilization, product
      concentration and buffer consumption. A simplified economic evaluation showed
      that CaptureSMB could decrease resin costs of 10-30% depending on the
      manufacturing scenario. 

PMID- 25748538
TI  - Wide injection zone compression in gradient reversed-phase liquid chromatography.
AB  - Chromatographic zone broadening is a common issue in microfluidic chromatography,
      where the sample volume introduced on column often exceeds the column void
      volume. To better understand the propagation of wide chromatographic zones on a
      separation device, a series of MS Excel spreadsheets were developed to simulate
      the process. To computationally simplify these simulations, we investigated the
      effects of injection related zone broadening and its gradient related zone
      compression by tracking only the movements of zone boundaries on column. The
      effects of sample volume, sample solvent, gradient slope, and column length on
      zone broadening were evaluated and compared to experiments performed on 0.32mm
      I.D. microfluidic columns. The repetitive injection method (RIM) was implemented
      to generate experimental chromatograms where large sample volume scenarios can be
      emulated by injecting two discrete small injection plugs spaced in time. A good
      match between predicted and experimental RIM chromatograms was observed. We
      discuss the performance of selected retention models on the accuracy of
      predictions and use the developed spreadsheets for illustration of gradient zone
      focusing for both small molecules and peptides. 

PMID- 25748539
TI  - Sigmapider diagram: a universal and versatile approach for system comparison and
      classification: application to solvent properties.
AB  - Classification methods based on physico-chemical properties are very useful in
      analytical chemistry, both for extraction and separation processes. Depending on
      the number of parameters, several classification approaches can be used: by
      plotting two- or three-dimensional maps (triangles, cubes, spheres); by
      calculating comparison values for one system with reference to another one, i.e.
      the ranking factor F, or the Neue selectivity difference s(2); or with
      chemometric methods (principal component analysis-PCA or hierarchical cluster
      analysis-HCA). All these methods display advantages and drawbacks: some of them
      are limited by the number of studied parameters (e.g. three for triangle or
      sphere plots); others require a new calculation when changing the reference point
      (F; s(2)), while for chemometric methods (PCA, HCA), the relationships between
      the clusters and the physico-chemical properties are not always easily
      understandable. From previous studies performed in supercritical fluid
      chromatography for stationary phase classification on the basis of linear
      solvation energy relationships (LSER) including five parameters, we developed a
      classification map called the Sigmapider diagram. This diagram allows plotting in
      a two-dimensional map the location of varied systems, having as many parameters
      as the ones required getting a satisfactory classification. It can be three,
      five, eight, or any number. In the present paper, we apply this diagram, and the
      calculation mode to obtain this diagram, to different solvent classifications:
      Snyder triangle, solvatochromic solvent selectivity, Hansen parameters, and also
      to LSER Abraham descriptors and COSMO-RS parameters. The new figure based on
      Snyder data does not change the global view of groups, except by the use of
      corrected data from literature, and allows adding the polarity value onto the
      map. For the solvatochromic solvent selectivity, it leads to achieve a better
      view of solvents having no acidic character. For Hansen parameters, the
      "flattening" of the spherical view down to a single plane could be found easier
      to use. For COSMO-RS and with Abraham descriptor, a more subtle classification is
      achieved, mainly due to the use of five parameters instead of three. A strong
      reversed correlation is established between the Rohrschneider polarity P' and the
      normalized V (molecular volume) parameter. The study of the location of solvents
      used for reversed-phase liquid chromatography and the Arizona system for counter
      current chromatography is discussed, as well as the replacement of unsafe
      solvents by greener ones, or the use of these classifications for the study of
      compound solubility. Besides, this paper also shows the ability to the spider
      diagram to plot on a single plane three axes from principal component analyses. 

PMID- 25748540
TI  - The role of methanol addition to water samples in reducing analyte adsorption and
      matrix effects in liquid chromatography-tandem mass spectrometry.
AB  - Liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis coupled simply
      with water filtering before injection has proven to be a simple, economic and
      time-saving method for analyzing trace-level organic pollutants in aqueous
      environments. However, the linearity, precision and detection limits of such
      methods for late-eluting analytes were found to be much poorer than for early
      eluting ones due to adsorption of the analytes in the operating system, such as
      sample vial, flow path and sample loop, creating problems in quantitative
      analysis. Addition of methanol (MeOH) into water samples as a modifier was shown
      to be effective in alleviating or even eliminating the negative effect on signal
      intensity for the late-eluting analytes and at the same time being able to reduce
      certain matrix effects for real water samples. Based on the maximum detection
      signal intensity obtained on desorption of the analytes with MeOH addition, the
      ratio of the detection signal intensity without addition of MeOH to the maximum
      intensity can be used to evaluate the effectiveness of methanol addition.
      Accordingly, the values of <50%, 50-80%, 80-120% could be used to indicate
      strong, medium and no effects, respectively. Based on this concept, an external
      matrix-matched calibration method with the addition of MeOH has been successfully
      established for analyzing fifteen pesticides with diverse physico-chemical
      properties in surface and groundwater with good linearity (r(2): 0.9929-0.9996),
      precision (intra-day relative standard deviation (RSD): 1.4-10.7%, inter-day RSD:
      1.5-9.4%), accuracy (76.9-126.7%) and low limits of detection (0.003-0.028MUg/L).

PMID- 25748541
TI  - High-performance liquid chromatographic enantioseparation of unusual amino acid
      derivatives with axial chirality on polysaccharide-based chiral stationary
      phases.
AB  - The successful enantioseparation of axially chiral amino acid derivatives
      containing a cyclohexylidene moiety on an analytical and semipreparative scale
      was achieved for the first time by HPLC using polysaccharide-based chiral
      stationary phases. Racemic methyl N-benzoylamino esters, easily obtained by
      methanolysis of the corresponding 5(4H)-oxazolones, were subjected to chiral HPLC
      resolution using chiral stationary phases based on immobilized 3,5
      dimethylphenylcarbamate derivatives of amylose (Chiralpak((r)) IA column) or
      cellulose (Chiralpak((r)) IB column). The behaviour of both selectors under
      different elution conditions was evaluated and compared. The amylose column
      showed better performance than the cellulose column for all enantiomers tested.
      The semipreparative resolution of axially chiral amino acid derivatives with
      different side chains has been achieved on a 250mm*20mm ID Chiralpak((r)) IA
      column using the appropriate mixture of n-hexane/chlorofom/ethanol as eluent by
      successive injections of a solution of the sample in chloroform. Using this
      protocol up to 120mg of each enantiomer of the corresponding axially chiral amino
      acid derivative were obtained from 300mg of racemate. [(Sa)-2a, 105mg; (Ra)-2a,
      60mg, [(Sa)-2b, 105mg; (Ra)-2b, 90mg, [(Sa)-2c, 120mg; (Ra)-2c, 100mg]. 

PMID- 25748542
TI  - Isotopologue ratio normalization for non-targeted metabolomics.
AB  - Robust quantification of analytes is a prerequisite for meaningful metabolomics
      experiments. In non-targeted metabolomics it is still hard to compare
      measurements across multiple batches or instruments. For targeted analyses
      isotope dilution mass spectrometry is used to provide a robust normalization
      reference. Here, we present an approach that allows for the automated semi
      quantification of metabolites relative to a fully stable isotope-labeled
      metabolite extract. Unlike many previous approaches, we include both identified
      and unidentified compounds in the data analysis. The internal standards are
      detected in an automated manner using the non-targeted tracer fate detection
      algorithm. The ratios of the light and heavy form of these compounds serve as a
      robust measure to compare metabolite levels across different mass spectrometric
      platforms. As opposed to other methods which require high resolution mass
      spectrometers, our methodology works with low resolution mass spectrometers as
      commonly used in gas chromatography electron impact mass spectrometry (GC-EI-MS)
      based metabolomics. We demonstrate the validity of our method by analyzing
      compound levels in different samples and show that it outperforms conventional
      normalization approaches in terms of intra- and inter-instrument reproducibility.
      We show that a labeled yeast metabolite extract can also serve as a reference for
      mammalian metabolite extracts where complete stable isotope labeling is hard to
      achieve. 

PMID- 25748543
TI  - Trace-chitosan-wrapped multi-walled carbon nanotubes as a new sorbent in
      dispersive micro solid-phase extraction to determine phenolic compounds.
AB  - This report describes the use of trace-chitosan-wrapped multi-walled carbon
      nanotubes (CS-MWCNTs) as a sorbent material in dispersive micro solid-phase
      extraction (DMSPE), which was combined with ultra-high-performance liquid
      chromatography coupled with quadrupole time-of-flight tandem mass spectrometry to
      analyze phenolic compounds in chrysanthemum tea and a chrysanthemum beverage. In
      this study, for the first time, CS-MWCNTs were used as a sorbent for this
      microextraction mode. Moreover, the proposed method exhibits the advantages of
      simplicity, rapidity, small sample amount and ease of operation. Furthermore, all
      of the important parameters that affect the extraction efficiency, such as the
      sorbent, pH, extraction time and type of elution solvent, were investigated and
      optimized in the DMSPE. Under the optimized extraction condition, the limit of
      detection, which was calculated based on a signal-to-noise ratio of 3, was 0.22
      16.19ngmL(-1). Satisfactory recovery values of 89-106% were obtained for the
      tested samples. The results show that the developed method was successfully
      applied to determine the content of chlorogenic acid and flavonoids in complex
      chrysanthemum samples. 

PMID- 25748544
TI  - Telehealth program for type 2 diabetes: usability, satisfaction, and clinical
      usefulness in an urban community health center.
AB  - BACKGROUND: We examined the usability, satisfaction, and clinical impact of a 3
      month diabetes telehealth intervention for poorly controlled type 2 diabetes
      (T2D) patients. The urban community health center sample (n=30) was 56.7% female,
      mean age of 60.6 years, 56.7% high school education or higher, and 73% African
      American and 26% Latino. MATERIALS AND METHODS: We integrated an electronic
      pillbox into an existing diabetes remote home monitoring (RHM) device suite
      comprising a Bluetooth((r)) (Bluetooth SIG, Kirkland, WA)-enabled blood glucose
      meter and an automatic blood pressure monitor connected to a cellular hub for
      data upload to our clinical application. This telehealth program involved minimal
      clinician training and functioned as a nonurgent patient self-management support
      service to increase the scope of clinic services. Telehealth nurse
      interventionists received regular RHM data alerts and called patients by phone at
      scheduled intervals. A graphical report summarizing patient RHM data was sent to
      providers to inform clinical decision making during a scheduled clinic visit at
      the 3-month follow-up. RESULTS: The results showed consistently high levels of
      RHM device use during the intervention period, high ratings of usability and
      program satisfaction from patients, and high ratings of provider satisfaction
      with the program. There was a clinically and statistically significant
      improvement in blood glucose control at 3 months, such that hemoglobin A1c
      improved 0.6% from a baseline level of 8.3% (p<0.05). CONCLUSIONS: These findings
      provide encouraging empirical support for the usability and clinical value of a
      diabetes telehealth program integrating a user-friendly cellular pillbox and
      clinical decision support tools that was delivered to an urban poor T2D clinic
      population.

PMID- 25748545
TI  - 4th congress of the international foot and ankle biomechanics community.

PMID- 25748546
TI  - In silico design of low molecular weight protein-protein interaction inhibitors:
      Overall concept and recent advances.
AB  - Protein-protein interactions (PPIs) are carrying out diverse functions in living
      systems and are playing a major role in the health and disease states. Low
      molecular weight (LMW) "drug-like" inhibitors of PPIs would be very valuable not
      only to enhance our understanding over physiological processes but also for drug
      discovery endeavors. However, PPIs were deemed intractable by LMW chemicals
      during many years. But today, with the new experimental and in silico
      technologies that have been developed, about 50 PPIs have already been inhibited
      by LMW molecules. Here, we first focus on general concepts about protein-protein
      interactions, present a consensual view about ligandable pockets at the protein
      interfaces and the possibilities of using fast and cost effective structure-based
      virtual screening methods to identify PPI hits. We then discuss the design of
      compound collections dedicated to PPIs. Recent financial analyses of the field
      suggest that LMW PPI modulators could be gaining momentum over biologics in the
      coming years supporting further research in this area. 

PMID- 25748547
TI  - Strategies to interfere with PDZ-mediated interactions in neurons: What we can
      learn from the rabies virus.
AB  - PDZ (PSD-95/Dlg/ZO-1) domains play a major role in neuronal homeostasis in which
      they act as scaffold domains regulating cellular trafficking, self-association
      and catalytic activity of essential proteins such as kinases and phosphatases.
      Because of their central role in cell signaling, cellular PDZ-containing proteins
      are preferential targets of viruses to hijack cellular function to their
      advantage. Here, we describe how the viral G protein of the rabies virus
      specifically targets the PDZ domain of neuronal enzymes during viral infection.
      By disrupting the complexes formed by cellular enzymes and their ligands, the
      virus triggers drastic effect on cell signaling and commitment of the cell to
      either survival (virulent strains) or death (vaccinal strains). We provide
      structural and biological evidences that the viral proteins act as competitors
      endowed with specificity and affinity in an essential cellular process by
      mimicking PDZ binding motif of cellular partners. Disruption of critical
      endogenous protein-protein interactions by viral protein drastically alters
      intracellular protein trafficking and catalytic activity of cellular proteins
      that control cell homeostasis. This work opens up many perspectives to mimic
      viral sequences and developing innovative therapies to manipulate cellular
      homeostasis. 

PMID- 25748548
TI  - Genotypic Variability of HIV-1 Reverse Transcriptase Gene from Long-Term
      Antiretroviral-Experienced Patients in Kenya.
AB  - There is continuous need to track genetic profiles of HIV strains circulating in
      different geographic settings to hasten vaccine discovery and inform public
      health and intervention policies. We partially sequenced the reverse
      transcriptase region of the HIV-1 pol gene from a total of 54 Kenyan patients
      aged 18-56 years who continued highly active antiretroviral treatment (HAART) for
      between 8 and 102 months. Subtyping was done using both the JPHMM tool and
      phylogenetic method. HIV-1 subtype A1 was the predominant strain in circulation,
      representing 57.4% and 70.4% of all isolates as determined by JPHMM and
      phylogenetic methods, respectively. Subtypes D (14.8%, 7.4%), C (5.6%, 9.3%), and
      A2 (0%, 5.6%) were determined at respective prevalence by both methods. JPHMM
      identified 22.2% of the isolates as recombinants. This surveillance focused on
      the RT gene and reaffirms the predominance of subtype A and an increasing
      proportion of recombinant strains in the Kenyan epidemic. 

PMID- 25748549
TI  - Strengthening And stretching for Rheumatoid Arthritis of the Hand (SARAH). A
      randomised controlled trial and economic evaluation.
AB  - BACKGROUND: The effectiveness of exercise for improving hand and wrist function
      in people with rheumatoid arthritis (RA) is uncertain. OBJECTIVES: The study aims
      were (1) to estimate the clinical effectiveness and cost-effectiveness of adding
      an optimised exercise programme for hands and upper limbs to standard care for
      patients with RA; and (2) to qualitatively describe the experience of
      participants in the trial with a particular emphasis on acceptability of the
      intervention, exercise behaviours and reasons for adherence/non-adherence.
      DESIGN: A pragmatic, multicentred, individually randomised controlled trial with
      an embedded qualitative study. Outcome assessors were blind to group assignment
      and independent of treatment delivery. SETTING: Seventeen NHS trusts in England
      comprising 21 rheumatology and therapy departments. PARTICIPANTS: Adults with RA
      who had pain and dysfunction of the hands and/or wrists and had been on stable
      medication for at least 3 months. Patients were excluded if they were under 18
      years old, had undergone upper limb surgery/fracture in the last 6 months, were
      on a waiting list for upper limb surgery or were pregnant. INTERVENTIONS: Usual
      care or usual care plus an individualised exercise programme. Usual care
      consisted of joint protection education, general exercise advice and functional
      splinting if required. The exercise programme consisted of six sessions of
      strengthening and stretching exercises with a hand therapist, daily home
      exercises and strategies to maximise adherence. MAIN OUTCOME MEASURES: The
      primary outcome was the Michigan Hand Outcome Questionnaire (MHQ) overall hand
      function subscale score at 12 months. Secondary outcome measures included the
      full MHQ, pain, health-related quality of life (Short Form questionnaire-12
      items), impairment (grip strength, dexterity and range of motion) and self
      efficacy. European Quality of Life-5 Dimensions, medication and health-care use
      were collected for the health economics evaluation. Follow-up was at 4 and 12
      months post randomisation. Analysis was performed on an intention-to-treat basis.
      RESULTS: We randomised 490 patients (244 to usual care, 246 to exercise
      programme). Compliance with the treatments was very good (93% of usual care
      participants and 75% of exercise programme participants completed treatment).
      Outcomes were obtained for 89% of participants at 12 months (222 for usual care,
      216 for exercise programme). There was a statistically significant difference in
      favour of the exercise programme for the primary outcome at 4 and 12 months [mean
      difference 4.6 points, 95% confidence interval (CI) 2.2 to 7.0 points; and mean
      difference 4.4 points, 95% CI 1.6 to 7.1 points, respectively]. There were no
      significant differences in pain scores or adverse events. The estimated
      difference in mean quality-adjusted life-years (QALYs) accrued over 12 months was
      0.01 greater (95% CI -0.03 to 0.05) in the exercise programme group. Imputed
      analysis produced incremental cost-effectiveness ratio estimates of L17,941 (0.59
      probability of cost-effectiveness at willingness-to-pay threshold of L30,000 per
      QALY). The qualitative study found the exercise programme to be acceptable and
      highlighted the importance of the therapist in enabling patients to establish a
      routine and incorporate the exercises into their lives. CONCLUSIONS: The results
      of the Strengthening And stretching for Rheumatoid Arthritis of the Hand trial
      suggest that the addition of an exercise programme for RA hands/wrists to usual
      care is clinically effective and cost-effective when compared with usual care
      alone. No adverse effects were associated with the exercise programme. The
      economic analysis suggests that the intervention is likely to be cost-effective.
      STUDY REGISTRATION: Current Controlled Trials ISRCTN 89936343.

PMID- 25748551
TI  - Invasive measures of myocardial perfusion and ischemia.
AB  - Until recently, our understanding of coronary artery disease (CAD) has been
      largely based on a purely anatomical approach as derived from the invasive
      angiogram. The confirmation of the diagnosis of "significant" CAD, the assessment
      of its extent, the risk stratification of patients, the therapeutic decisions,
      the definition of study end-points, and the validation of non-invasive testing,
      all mainly relied on "eyeballing" the angiogram, i.e. a subjective evaluation of
      the presence of at least 50% (or 70%) diameter stenosis.With the development of
      invasive, wire-based, means to quantify coronary pressure and flow with high
      spatial resolution, one realized that purely angiographic metrics correlated
      poorly with functional information. Currently, it is admitted that both
      anatomical and functional information are needed to define CAD and to optimize
      its management. In the present review, we summarize the main characteristics of
      invasive functional indices of ischemia and perfusion. 

PMID- 25748550
TI  - Trovafloxacin-induced replication stress sensitizes HepG2 cells to tumor necrosis
      factor-alpha-induced cytotoxicity mediated by extracellular signal-regulated
      kinase and ataxia telangiectasia and Rad3-related.
AB  - Use of the fluoroquinolone antibiotic trovafloxacin (TVX) was restricted due to
      idiosyncratic, drug-induced liver injury (IDILI). Previous studies demonstrated
      that tumor necrosis factor-alpha (TNF) and TVX interact to cause death of
      hepatocytes in vitro that was associated with prolonged activation of c-Jun N
      terminal kinase (JNK), activation of caspases 9 and 3, and DNA damage. The
      purpose of this study was to explore further the mechanism by which TVX interacts
      with TNF to cause cytotoxicity. Treatment with TVX caused cell cycle arrest,
      enhanced expression of p21 and impaired proliferation, but cell death only
      occurred after cotreatment with TVX and TNF. Cell death involved activation of
      extracellular signal-related kinase (ERK), which in turn activated caspase 3 and
      ataxia telangiectasia and Rad3-related (ATR), both of which contributed to
      cytotoxicity. Cotreatment of HepG2 cells with TVX and TNF caused double-strand
      breaks in DNA, and ERK contributed to this effect. Inhibition of caspase activity
      abolished the DNA strand breaks. The data suggest a complex interaction of TVX
      and TNF in which TVX causes replication stress, and the downstream effects are
      exacerbated by TNF, leading to hepatocellular death. These results raise the
      possibility that IDILI from TVX results from MAPK and ATR activation in
      hepatocytes initiated by interaction of cytokine signaling with drug-induced
      replication stress.

PMID- 25748552
TI  - Cilostazol induces vasodilation through the activation of Ca(2+)-activated K(+)
      channels in aortic smooth muscle.
AB  - We investigated the vasorelaxant effect of cilostazol and related signaling
      pathways in phenylephrine (Phe)-induced pre-contracted aortic rings. Cilostazol
      induced vasorelaxation in a concentration-dependent manner when aortic rings were
      pre-contracted with Phe. Application of the voltage-dependent K(+) (Kv) channel
      inhibitor 4-AP, the ATP-sensitive K(+) (K(ATP)) channel inhibitor glibenclamide,
      and the inwardly rectifying K(+) (Kir) channel inhibitor Ba(2+) did not alter the
      vasorelaxant effect of cilostazol; however, pre- and post-treatment with the big
      conductance Ca(2+)-activated K(+) (BK(Ca)) channel inhibitor paxilline inhibited
      the vasorelaxant effect of cilostazol. This vasorelaxant effect of cilostazol was
      reduced in the presence of an adenylyl cyclase or a protein kinase A (PKA)
      inhibitor, but not a protein kinase G inhibitor. Inside-out single channel
      recordings revealed that cilostazol induced the activation of BK(Ca) channel
      activity. The vasorelaxant effect of cilostazol was not affected by removal of
      the endothelium. In addition, application of a nitric oxide synthase inhibitor
      and a small-conductance Ca(2+)-activated K(+) (SK(Ca)) channel inhibitor did not
      affect cilostazol-induced vasorelaxation. We conclude that cilostazol induced
      vasorelaxation of the aorta through activation of BK(Ca) channel via a PKA
      dependent signaling mechanism independent of endothelium.

PMID- 25748553
TI  - In vitro activity of ceftazidime, ceftaroline and aztreonam alone and in
      combination with avibactam against European Gram-negative and Gram-positive
      clinical isolates.
AB  - Recent clinical isolates of key Gram-negative and Gram-positive bacteria were
      collected in 2012 from hospitalised patients in medical centres in four European
      countries (France, Germany, Italy and Spain) and were tested using standard broth
      microdilution methodology to assess the impact of 4 mg/L avibactam on the in
      vitro activities of ceftazidime, ceftaroline and aztreonam. Against
      Enterobacteriaceae, addition of avibactam significantly enhanced the level of
      activity of these antimicrobials. MIC(90) values (minimum inhibitory
      concentration that inhibits 90% of the isolates) of ceftazidime, ceftaroline and
      aztreonam for Escherichia coli, Klebsiella pneumoniae, Enterobacter cloacae,
      Enterobacter aerogenes, Citrobacter freundii and Morganella morganii were reduced
      up to 128-fold or greater when combined with avibactam. A two-fold reduction in
      the MIC(90) of ceftazidime to 8 mg/L was noted in Pseudomonas aeruginosa isolates
      when combined with avibactam, whereas little effect of avibactam was noted on the
      MIC values of the test compounds when tested against Acinetobacter baumannii
      isolates. Avibactam had little effect on the excellent activity of ceftazidime,
      ceftaroline and aztreonam against Haemophilus influenzae. It had no impact on the
      in vitro activity of ceftazidime and ceftaroline against staphylococci and
      streptococci. This study demonstrates that addition of avibactam enhances the
      activities of ceftazidime, ceftaroline and aztreonam against Enterobacteriaceae
      and P. aeruginosa but not against A. baumannii.

PMID- 25748554
TI  - Association of haemolytic uraemic syndrome with dysregulation of chemokine
      receptor expression in circulating monocytes.
AB  - Haemolytic uraemic syndrome (HUS) is the major complication of Escherichia coli
      gastrointestinal infections that are Shiga toxin (Stx) producing. Monocytes
      contribute to HUS evolution by producing cytokines that sensitize endothelial
      cells to Stx action and migration to the injured kidney. As CC chemokine
      receptors (CCRs) are involved in monocyte recruitment to injured tissue, we
      analysed the contribution of these receptors to the pathogenesis of HUS. We
      analysed CCR1, CCR2 and CCR5 expression in peripheral monocytes from HUS patients
      during the acute period, with healthy children as controls. We observed an
      increased expression of CCRs per cell in monocytes from HUS patients, accompanied
      by an increase in the absolute number of monocytes CCR1+, CCR2+ and CCR5+. It is
      interesting that prospective analysis confirmed that CCR1 expression positively
      correlated with HUS severity. The evaluation of chemokine levels in plasma showed
      that regulated on activation of normal T-cell-expressed and -secreted (RANTES)
      protein was reduced in plasma from patients with severe HUS, and this decrease
      correlated with thrombocytopenia. Finally, the expression of the higher CCRs was
      accompanied by a loss of functionality which could be due to a mechanism for
      desensitization to compensate for altered receptor expression. The increase in
      CCR expression correlates with HUS severity, suggesting that the dysregulation of
      these receptors might contribute to an increased risk of renal damage. Activated
      monocytes could be recruited by chemokines and then receptors could be
      dysregulated. The dysregulation of CCRs and their ligands observed during the
      acute period suggests that a chemokine pathway would participate in HUS
      development. 

PMID- 25748555
TI  - Upregulated RIP3 Expression Potentiates MLKL Phosphorylation-Mediated Programmed
      Necrosis in Toxic Epidermal Necrolysis.
AB  - Toxic epidermal necrolysis (TEN) is a severe adverse drug reaction involving
      extensive keratinocyte death in the epidermis. Histologically, the skin from TEN
      patients exhibits separation at the dermo-epidermal junction and accompanying
      necrosis of epidermal keratinocytes. Receptor-interacting protein kinase-3 (RIP3
      or RIPK3) is an essential part of the cellular machinery that executes
      "programmed", or "regulated", necrosis and has a key role in spontaneous cell
      death and inflammation in keratinocytes under certain conditions. Here we show
      that RIP3 expression is highly upregulated in skin sections from TEN patients and
      may therefore contribute to the pathological damage in TEN through activation of
      programmed necrotic cell death. The expression level of mixed lineage kinase
      domain-like protein (MLKL), a key downstream component of RIP3, was not
      significantly different in skin lesions of TEN. However, elevated MLKL
      phosphorylation was observed in the skin from TEN patients, indicating the
      presence of RIP3-dependent programmed necrosis. Importantly, in an in vitro model
      of TEN, dabrafenib, an inhibitor of RIP3, prevented RIP3-mediated MLKL
      phosphorylation and decreased cell death. Results from this study suggest that
      the high expression of RIP3 in keratinocytes from TEN patients potentiates MLKL
      phosphorylation/activation and necrotic cell death. Thus, RIP3 represents a
      potential target for treatment of TEN. 

PMID- 25748556
TI  - Acne Treatment Based on Selective Photothermolysis of Sebaceous Follicles with
      Topically Delivered Light-Absorbing Gold Microparticles.
AB  - The pathophysiology of acne vulgaris depends on active sebaceous glands, implying
      that selective destruction of sebaceous glands could be an effective treatment.
      We hypothesized that light-absorbing microparticles could be delivered into
      sebaceous glands, enabling local injury by optical pulses. A suspension of
      topically applied gold-coated silica microparticles exhibiting plasmon resonance
      with strong absorption at 800 nm was delivered into human pre-auricular and swine
      sebaceous glands in vivo, using mechanical vibration. After exposure to 10-50 J
      cm(-2), 30 milliseconds, 800 nm diode laser pulses, microscopy revealed
      preferential thermal injury to sebaceous follicles and glands, consistent with
      predictions from a computational model. Inflammation was mild; gold particles
      were not retained in swine skin 1 month after treatment, and uptake in other
      organs was negligible. Two independent prospective randomized controlled clinical
      trials were performed for treatment of moderate-to-severe facial acne, using
      unblinded and blinded assessments of disease severity. Each trial showed
      clinically and statistically significant improvement of inflammatory acne
      following three treatments given 1-2 weeks apart. In Trial 2, inflammatory
      lesions were significantly reduced at 12 weeks (P=0.015) and 16 weeks (P=0.04)
      compared with sham treatments. Optical microparticles enable selective
      photothermolysis of sebaceous glands. This appears to be a well-tolerated,
      effective treatment for acne vulgaris. 

PMID- 25748557
TI  - The association between negative symptoms, psychotic experiences and later
      schizophrenia: a population-based longitudinal study.
AB  - BACKGROUND: Psychotic experiences are common in the general population, and
      predict later psychotic illness. Much less is known about negative symptoms in
      the general population. METHOD: This study utilized a sample of 4,914 Israel-born
      individuals aged 25-34 years who were screened for psychopathology in the 1980's.
      Though not designed to specifically assess negative symptoms, data were available
      on 9 self-report items representing avolition and social withdrawal, and on 5
      interviewer-rated items assessing speech deficits, flat affect and poor hygiene.
      Psychotic experiences were assessed using the False Beliefs and Perceptions
      subscale of the Psychiatric Epidemiology Research Interview. Psychiatric
      hospitalization was ascertained 24 years later using a nation-wide psychiatric
      hospitalization registry. RESULTS: After removing subjects with diagnosable
      psychotic disorders at baseline, 20.2% had at least one negative symptom.
      Negative symptoms were associated with increased risk of later schizophrenia only
      in the presence of strong (frequent) psychotic experiences (OR = 13.0, 9% CI: 2.1
      79.4). CONCLUSIONS: Negative symptoms are common in the general population,
      though the majority of people with negative symptoms do not manifest a clinically
      diagnosed psychiatric disorder. Negative symptoms and psychotic experiences
      critically depend on each other's co-occurrence in increasing risk for later
      schizophrenia.

PMID- 25748558
TI  - Chronic balance disorders after acoustic neuroma surgery: assessment of
      gravitational vertical perception.
AB  - CONCLUSION: The head tilt response (HTR) test performed in a group of patients
      with chronic dizziness after acoustic neuroma surgery showed alterations in the
      gravitational vertical perception (GV). OBJECTIVE: The assessment of the accuracy
      in the GV through the HTR test in patients with long-term balance disorders after
      acoustic neuroma surgery. METHODS: The HTR was performed in two groups of
      patients that had undergone acoustic neuroma surgery: six uncompensated patients
      (UPs) who maintained vestibular symptoms 1 year after surgery and two compensated
      patients (CPs) without vestibular symptoms. Twelve healthy control adults were
      also tested (control group, CG). Three parameters were measured in the HTR test:
      steady-state error (SSE), rise time (TRS), and mean energy of the error signal
      per step (MEE). RESULTS: The UP group showed higher values for the TRS and MEE
      parameters compared with the CG (p < 0.05) when performing the HTR test to the
      side of the lesion and to the contralateral side, while the SSE only showed
      significant higher values when the patient estimated the GV towards the side of
      the lesion. The two patients in the CP group did not have differences in the
      three parameters assessed when compared with the CG.

PMID- 25748559
TI  - A systematic review of mechanisms of change in mindfulness-based cognitive
      therapy in the treatment of recurrent major depressive disorder.
AB  - BACKGROUND: The investigation of treatment mechanisms in randomized controlled
      trials has considerable clinical and theoretical relevance. Despite the empirical
      support for the effect of mindfulness-based cognitive therapy (MBCT) in the
      treatment of recurrent major depressive disorder (MDD), the specific mechanisms
      by which MBCT leads to therapeutic change remain unclear. OBJECTIVE: By means of
      a systematic review we evaluate how the field is progressing in its empirical
      investigation of mechanisms of change in MBCT for recurrent MDD. METHOD: To
      identify relevant studies, a systematic search was conducted. Studies were coded
      and ranked for quality. RESULTS: The search produced 476 articles, of which 23
      were included. In line with the theoretical premise, 12 studies found that
      alterations in mindfulness, rumination, worry, compassion, or meta-awareness were
      associated with, predicted or mediated MBCT's effect on treatment outcome. In
      addition, preliminary studies indicated that alterations in attention, memory
      specificity, self-discrepancy, emotional reactivity and momentary positive and
      negative affect might play a role in how MBCT exerts its clinical effects.
      CONCLUSION: The results suggest that MBCT could work through some of the MBCT
      model's theoretically predicted mechanisms. However, there is a need for more
      rigorous designs that can assess greater levels of causal specificity.

PMID- 25748560
TI  - Prevalence of HIV, HCV, and High-Risk Behaviors for Substance Users in Drop in
      Centers in Southern Iran.
AB  - OBJECTIVES: Drop In Centers (DICs) are organizations in which health and social
      services are delivered to drug users on the basis of harm-reduction strategies.
      The aim of this epidemiological study was to estimate the prevalence of human
      immunodeficiency virus (HIV) and hepatitis C virus (HCV) infection at these
      centers over a 6-year period. METHODS: All of the DICs (7 in total) visited were
      located in Shiraz, the capital city of Fars province, southern Iran. Every
      patient record in these centers was studied between April 2006 and April 2011.
      Complementary information on the frequency of HIV was collected from the
      Voluntary Counseling and Testing services. A logistic regression model was
      applied to data analysis. The study explored risk factors associated with HIV and
      HCV infections, which were primarily high-risk sexual behavior. RESULTS: This
      study examined 1,327 people, 79.5% of whom were males. The mean age of first
      substance use and the first injection among intravenous drug users (IDUs) were
      20.24 +/- 6.11 and 26.5 +/- 7.3 years, respectively. In total, 13.5% and 20.2% of
      the subjects who registered at the DICs were infected with HCV and HIV,
      respectively. Shared injection, history of imprisonment, maleness, unsafe sex,
      inadequate housing, and low education were risk factors for HIV infection. Shared
      injection, unsafe sex, history of imprisonment, and maleness were predisposing
      factors for HCV infection. A history of imprisonment and substance use upon
      registration at the DIC were significant risk factors for female sex workers.
      CONCLUSIONS: Our study emphasized the implementation of preventive measures like
      education and needle exchange program as harm-reduction strategies. Drop in
      Centers are important for the management of health problems, including HIV
      infection and social problems such as crime. Periodic epidemiological studies on
      DICs are necessary to monitor and modulate the services delivered by these
      centers.

PMID- 25748561
TI  - Prevalent intravenous abuse of methylphenidate among treatment-seeking patients
      with substance abuse disorders: a descriptive population-based study.
AB  - OBJECTIVES: Prescription rates of methylphenidate (MPH) are sharply rising in
      most Western countries. Although it has been reported that MPH has abuse
      potential, little is known about the prevalence of intravenous (IV) abuse of MPH.
      The aim of the study was to investigate the prevalence of IV MPH abuse among
      treatment-seeking IV substance abusers in Iceland. METHODS: This is a descriptive
      population-based study using a semistructured interview assessing
      sociodemographics, substance abuse history, and the method of administration of
      108 IV substance abusers. During 1 year, consecutively admitted adult inpatients
      with substance use disorder at any detoxification center in Iceland that reported
      any IV substance abuse in the past 30 days were invited to participate. Abuse was
      defined as nontherapeutic use of a substance to gain psychological or
      physiological effect. RESULTS: Prevalence of any IV MPH abuse among participants
      was 88% in the last 30 days (95% confidence interval [CI], 0.82-0.94) and MPH was
      the most commonly abused substance (65%) and the preferred substance (63%).
      Around one third (30%) reported MPH as the first IV substance ever abused.
      However, among those reporting a shorter history than 10 years of IV abuse, 42%
      reported MPH as the first IV substance ever abused. CONCLUSIONS: This first
      nationwide study on IV abuse of MPH shows that it is common among treatment
      seeking IV abusers in Iceland and suggests that MPH has high abuse potential.
      Therefore, both the use and possible abuse of MPH in those with high abuse
      potential should be monitored, especially in countries where MPH prescriptions
      rates are on the rise.

PMID- 25748563
TI  - Novel transgenic lines to fluorescently label clathrin and caveolin endosomes in
      live zebrafish.

PMID- 25748562
TI  - Safety and pharmacokinetics of oral cannabidiol when administered concomitantly
      with intravenous fentanyl in humans.
AB  - OBJECTIVES: Cannabidiol (CBD) is hypothesized as a potential treatment for opioid
      addiction, with safety studies an important first step for medication
      development. We determined CBD safety and pharmacokinetics when administered
      concomitantly with a high-potency opioid in healthy subjects. METHODS: This
      double-blind, placebo-controlled cross-over study of CBD, coadministered with
      intravenous fentanyl, was conducted at the Clinical Research Center in Mount
      Sinai Hospital, a tertiary care medical center in New York City. Participants
      were healthy volunteers aged 21 to 65 years with prior opioid exposure,
      regardless of the route. Blood samples were obtained before and after 400 or 800
      mg of CBD pretreatment, followed by a single 0.5 (session 1) or 1.0 MUg/kg
      (session 2) of intravenous fentanyl dose. The primary outcome was the Systematic
      Assessment for Treatment Emergent Events (SAFTEE) to assess safety and adverse
      effects. CBD peak plasma concentrations, time to reach peak plasma concentrations
      (tmax), and area under the curve (AUC) were measured. RESULTS: SAFTEE data were
      similar between groups without respiratory depression or cardiovascular
      complications during any test session. After low-dose CBD, tmax occurred at 3 and
      1.5 hours in sessions 1 and 2, respectively. After high-dose CBD, tmax occurred
      at 3 and 4 hours in sessions 1 and 2, respectively. There were no significant
      differences in plasma CBD or cortisol (AUC P = NS) between sessions. CONCLUSIONS:
      Cannabidiol does not exacerbate adverse effects associated with intravenous
      fentanyl administration. Coadministration of CBD and opioids was safe and well
      tolerated. These data provide the foundation for future studies examining CBD as
      a potential treatment for opioid abuse.

PMID- 25748565
TI  - Venom-spraying behavior of the scorpion Parabuthus transvaalicus (Arachnida:
      Buthidae).
AB  - Many animals use chemical squirting or spraying behavior as a defensive response.
      Some members of the scorpion genus Parabuthus (family Buthidae) can spray their
      venom. We examined the stimulus control and characteristics of venom spraying by
      Parabuthus transvaalicus to better understand the behavioral context for its use.
      Venom spraying occurred mostly, but not always, when the metasoma (tail) was
      contacted (usually grasped by forceps), and was absent during stinging-like
      thrusts of the metasoma apart from contact. Scorpions were significantly more
      likely to spray when contact was also accompanied by airborne stimuli. Sprays
      happened almost instantaneously following grasping by forceps (median=0.23s) as a
      brief (0.07-0.30s, mean=0.18s), fine stream (<5 degrees  arc) that was not
      directed toward the stimulus source; however, rapid independent movements of the
      metasoma and/or telson (stinger) often created a more diffuse spray, increasing
      the possibility of venom contact with the sensitive eyes of potential scorpion
      predators. Successive venom sprays varied considerably in duration and velocity.
      Collectively, these results suggest that venom spraying might be useful as an
      antipredator function and can be modulated based on threat. 

PMID- 25748564
TI  - Placental DNA Methylation Related to Both Infant Toenail Mercury and Adverse
      Neurobehavioral Outcomes.
AB  - BACKGROUND: Prenatal mercury (Hg) exposure is associated with adverse child
      neurobehavioral outcomes. Because Hg can interfere with placental functioning and
      cross the placenta to target the fetal brain, prenatal Hg exposure can inhibit
      fetal growth and development directly and indirectly. OBJECTIVES: We examined
      potential associations between prenatal Hg exposure assessed through infant
      toenail Hg, placental DNA methylation changes, and newborn neurobehavioral
      outcomes. METHODS: The methylation status of > 485,000 CpG loci was interrogated
      in 192 placental samples using Illumina's Infinium HumanMethylation450 BeadArray.
      Hg concentrations were analyzed in toenail clippings from a subset of 41 infants;
      neurobehavior was assessed using the NICU Network Neurobehavioral Scales (NNNS)
      in an independent subset of 151 infants. RESULTS: We identified 339 loci with an
      average methylation difference > 0.125 between any two toenail Hg tertiles.
      Variation among these loci was subsequently found to be associated with a high
      risk neurodevelopmental profile (omnibus p-value = 0.007) characterized by the
      NNNS. Ten loci had p < 0.01 for the association between methylation and the high
      risk NNNS profile. Six of 10 loci reside in the EMID2 gene and were
      hypomethylated in the 16 high-risk profile infants' placentas. Methylation at
      these loci was moderately correlated (correlation coefficients range, -0.33 to 
      0.45) with EMID2 expression. CONCLUSIONS: EMID2 hypomethylation may represent a
      novel mechanism linking in utero Hg exposure and adverse infant neurobehavioral
      outcomes.

PMID- 25748566
TI  - Nebulized pentoxifylline for reducing the duration of oxygen supplementation in
      extremely preterm neonates.
AB  - OBJECTIVE: To evaluate the efficacy and safety of nebulized pentoxifylline for
      reducing the duration of oxygen supplementation in extremely preterm neonates at
      high risk of bronchopulmonary dysplasia (BPD). STUDY DESIGN: Single-center,
      randomized, double-blind, placebo-controlled trial was conducted. Infants of
      23(0) to 27(6) weeks' gestational age requiring mechanical ventilation or >=30%
      supplemental oxygen on continuous positive airway pressure at 72-168 hours were
      randomized to receive 20 mg/kg (1 mL/kg) nebulized pentoxifylline or an equal
      volume of normal saline placebo every 6 hours for 10 consecutive days via a
      vibrating mesh nebulizer. The primary outcome was the duration of oxygen
      supplementation at 40 weeks' postmenstrual age. We used Cox proportional hazards
      regression modeling to analyze outcomes. RESULTS: All infants had adequate data
      for analysis of the primary outcome. Intention-to-treat analysis revealed no
      differences in duration of oxygen supplementation at 40 weeks' postmenstrual age
      between pentoxifylline (n=41) and placebo (n=40) groups (median 2262 vs 2160
      hours, adjusted hazard ratio: 1.14, 95% CI 0.72-1.80, P=.63). There was no
      difference in mortality and further secondary outcomes. No adverse effects were
      noted. CONCLUSIONS: Nebulized pentoxifylline is safe but did not reduce the
      duration of oxygen supplementation in extremely preterm infants at high risk of
      BPD. Dose-ranging studies and large, well-designed clinical trials are required
      to determine whether the use of nebulized or systemic pentoxifylline as a
      prophylactic therapy offers small but relevant benefits for prevention of BPD.
      TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry:
      ACTRN12611000145909.

PMID- 25748567
TI  - Intranasal dexmedetomidine for sedation for pediatric computed tomography
      imaging.
AB  - This prospective observational pilot study evaluated the aerosolized intranasal
      route for dexmedetomidine as a safe, effective, and efficient option for infant
      and pediatric sedation for computed tomography imaging. The mean time to sedation
      was 13.4 minutes, with excellent image quality, no failed sedations, or
      significant adverse events. TRIAL REGISTRATION: Registered with
      ClinicalTrials.gov: NCT01900405.

PMID- 25748569
TI  - Dual emissions from ruthenium(II) complexes having 4-arylethynyl-1,10
      phenanthroline at low temperature.
AB  - A [Ru(phen)3](2+) complex (phen = 1,10-phenanthroline) having an arylethynyl
      group at the 4-position of one of the three phen ligands (aryl:
      (dimesityl)borylduryl group = [RuBE](2+) or duryl group = [RuDE](2+)) showed dual
      emissions at low temperature in propylene carbonate (PC). The shorter emission
      lifetime components (tau(em)(s) ~ 13 MUs) that originated from the lowest-energy
      excited triplet states (T1) of the complexes were almost independent of
      temperature (T = 77-320 K), while the longer emission lifetime components
      (tau(em)(l)), as the T2 emissions appeared below the fluid-to-glass transition
      temperature (Tg ~ 220 K) in PC, were almost constant at 27 MUs in the range of T
      = 77-220 K. The tau(em)(s) components of the complexes were assigned to the
      emissions from the metal-to-ligand charge transfer (MLCT) excited states
      possessing relatively large ligand-centered (LC) excited-state characters
      (T1(MLCT/LC)), while the tau(em)(l) components were shown to be originating from
      the T2(MLCT) excited states. The T2(MLCT) states of the complexes became
      nonemissive above Tg in PC due to fast nonradiative decay through solvent
      reorganization around the T2(MLCT) excited states. The photophysical properties
      of the complexes were also shown to be characterized by the presence of the
      arylethynyl units at the 4-positions of the phen ligands. 

PMID- 25748568
TI  - Vestibular Deficits following Youth Concussion.
AB  - OBJECTIVE: To characterize the prevalence and recovery of pediatric patients with
      concussion who manifest clinical vestibular deficits and to describe the
      correlation of these deficits with neurocognitive function, based on computerized
      neurocognitive testing, in a sample of pediatric patients with concussion.
      METHODS: This was a retrospective cohort study of patients ages 5-18 years with
      concussion referred to a tertiary pediatric hospital-affiliated sports medicine
      clinic from July 1, 2010 to December 31, 2011. A random sample of all eligible
      patient visits was obtained, and all related visits for those patients were
      reviewed. RESULTS: A total of 247 patients were chosen from 3740 eligible visits
      for detailed review and abstraction; 81% showed a vestibular abnormality on
      initial clinical examination. Those patients with vestibular signs on the initial
      examination took a significantly longer time to return to school (median 59 days
      vs 6 days, P=.001) or to be fully cleared (median 106 days vs 29 days, P=.001).
      They additionally scored more poorly on initial computerized neurocognitive
      testing, and it took longer for them to recover from neurocognitive deficits.
      Those patients with 3 or more previous concussions had a greater prevalence of
      vestibular deficits, and it took longer for those deficits to resolve.
      CONCLUSION: Vestibular deficits in children and adolescents with a history of
      concussion are highly prevalent. These deficits appear to be associated with
      extended recovery times and poorer performance on neurocognitive testing. Further
      studies evaluating the effectiveness of vestibular therapy on improving such
      deficits are warranted.

PMID- 25748570
TI  - Phase-contrast scanning transmission electron microscopy.
AB  - This report introduces the first results obtained using phase-contrast scanning
      transmission electron microscopy (P-STEM). A carbon-film phase plate (PP) with a
      small center hole is placed in the condenser aperture plane so that a phase shift
      is introduced in the incident electron waves except those passing through the
      center hole. A cosine-type phase-contrast transfer function emerges when the
      phase-shifted scattered waves interfere with the non-phase-shifted unscattered
      waves, which passed through the center hole before incidence onto the specimen.
      The phase contrast resulting in P-STEM is optically identical to that in phase
      contrast transmission electron microscopy that is used to provide high contrast
      for weak phase objects. Therefore, the use of PPs can enhance the phase contrast
      of the STEM images of specimens in principle. The phase shift resulting from the
      PP, whose thickness corresponds to a phase shift of pi, has been confirmed using
      interference fringes displayed in the Ronchigram of a silicon single crystal
      specimen. The interference fringes were found to abruptly shift at the edge of
      the PP hole by pi. 

PMID- 25748571
TI  - Prevalence and risk factors for trimethoprim-sulfamethoxazole-resistant
      Escherichia coli among women with acute uncomplicated urinary tract infection in
      a developing country.
AB  - BACKGROUND: Prospective studies from developing countries that have investigated
      risk factors for trimethoprim-sulfamethoxazole (TMP-SMX)-resistant Escherichia
      coli in women with uncomplicated urinary tract infection (UTI) remain scarce.
      METHODS: Women with acute uncomplicated UTI were enrolled prospectively. Urine
      was sent for antimicrobial susceptibility testing. Logistic regression analysis
      was used to identify risk factors for TMP-SMX resistance. RESULTS: Of 405
      participants, 229 (56.5%) had bacteriuria (mean age 31.9 +/- 9.5 years). In the
      previous 12 months, 77 (33.6%) had experienced at least one UTI episode and 106
      (46.3%) reported antimicrobial use. The most common uropathogens were E. coli
      (75.8%) and Staphylococcus saprophyticus (8.9%). For the 179 E. coli, resistance
      rates were highest for ampicillin (64.3%) and TMP-SMX (41.3%). Resistance to
      cephalosporins, nitrofurantoin, and fluoroquinolones was much lower compared with
      the hospital laboratory-based surveillance data. Risk factors for TMP-SMX
      resistance were UTI in the last 6 months (odds ratio 2.22; p = 0.04) and the
      number of UTI episodes in the past year (odds ratio 2.06; p = 0.004). The number
      of UTI episodes (adjusted odds ratio 2.21; p = 0.02) remained significant on
      multivariate analysis. CONCLUSIONS: TMP-SMX resistance was high. Number of
      previous UTI episodes was associated with increased risk of resistance; prior
      antimicrobial use was not. Hospital antibiograms should be used with caution when
      treating uncomplicated UTI.

PMID- 25748572
TI  - Regulation of store-operated Ca2+ entry activity by cell cycle dependent up
      regulation of Orai2 in brain capillary endothelial cells.
AB  - Store-operated Ca(2+) entry (SOCE) via Orai1 and STIM1 complex is supposed to
      have obligatory roles in the regulation of cellular functions of vascular
      endothelial cells, while little is known about the contribution of Orai2.
      Quantitative PCR and Western blot analyses indicated the expression of Orai2 and
      STIM2, in addition to Orai1 and STIM1 in bovine brain capillary endothelial cell
      line, t-BBEC117. During the exponential growth of t-BBEC117, the knockdown of
      Orai1 and STIM1 significantly reduced the SOCE activity, whereas Orai2 and STIM2
      siRNAs had no effect. To examine whether endogenous SOCE activity contributes to
      the regulation of cell cycle progression, t-BBEC117 were synchronized using
      double thymidine blockage. At the G2/M phase, Ca(2+) influx via SOCE was
      decreased and Orai2 expression was increased compared to the G0/G1 phase. When
      Orai2 was knocked down at the G2/M phase, the decrease in SOCE was removed, and
      cell proliferation was partly attenuated. Taken together, Orai1 significantly
      contributes to cell proliferation via the functional expression, which is
      presumably independent of the cell cycle phases. In construct, Orai2 is
      specifically up-regulated during the G2/M phase, negatively modulates the SOCE
      activity, and may contribute to the regulation of cell cycle progression in brain
      capillary endothelial cells. 

PMID- 25748573
TI  - Xylosyltransferase II is the predominant isoenzyme which is responsible for the
      steady-state level of xylosyltransferase activity in human serum.
AB  - In mammals, two active xylosyltransferase isoenzymes (EC 2.4.2.16) exist. Both
      xylosyltransferases I and II (XT-I and XT-II) catalyze the transfer of xylose
      from UDP-xylose to select serine residues in the proteoglycan core protein.
      Altered XT activity in human serum was found to correlate directly with various
      diseases such as osteoarthritis, systemic sclerosis, liver fibrosis, and
      pseudoxanthoma elasticum. To interpret the significance of the enzyme activity
      alteration observed in disease states it is important to know which isoenzyme is
      responsible for the XT activity in serum. Until now it was impossible for a
      specific measurement of XT-I or XT-II activity, respectively, because of the
      absence of a suitable enzyme substrate. This issue has now been solved and the
      following experimental study demonstrates for the first time, via the enzyme
      activity that XT-II is the predominant isoenzyme responsible for XT activity in
      human serum. The proof was performed using natural UDP-xylose as the xylose
      donor, as well as the artificial compound UDP-4-azido-4-deoxyxylose, which is a
      selective xylose donor for XT-I. 

PMID- 25748574
TI  - Identification of flavonoids and expression of flavonoid biosynthetic genes in
      two coloured tree peony flowers.
AB  - Tree peony (Paeonia suffruticosa Andr.) has been named the "king of flowers"
      because of its elegant and gorgeous flower colour. Among these colours, the
      molecular mechanisms of white formation and how white turned to red in P.
      suffruticosa is little known. In this study, flower colour variables, flavonoid
      accumulation and expression of flavonoid biosynthetic genes of white ('Xueta')
      and red ('Caihui') P. suffruticosa were investigated. The results showed that the
      flower colours of both cultivars were gradually deepened with the development of
      flowers. Moreover, two anthoxanthin compositions apigenin 7-O-glucoside together
      with apigenin deoxyheso-hexoside were identified in 'Xueta' and 'Caihui', but one
      main anthocyanin composition peonidin 3,5-di-O-glucoside (Pn3G5G) was only found
      in 'Caihui'. Total contents of anthocyanins in 'Caihui' was increased during
      flower development, and the same trend was presented in anthoxanthins and
      flavonoids of these two cultivars, but the contents of these two category
      flavonoid in 'Caihui' were always higher than those in 'Xueta'. Furthermore, nine
      structural genes in flavonoid biosynthetic pathway were isolated including the
      full-length cDNAs of phenylalanine ammonialyase gene (PAL), chalcone synthase
      gene (CHS) and chalcone isomerase gene (CHI), together with the partial-length
      cDNAs of flavanone 3-hydroxylase gene (F3H), flavonoid 3'-hydroxylase gene
      (F3'H), dihydroflavonol 4-reductase gene (DFR), anthocyanidin synthase gene
      (ANS), UDP-glucose: flavonoid 3-O-glucosyltransferase gene (UF3GT) and UDP
      glucose: flavonoid 5-O-glucosyltransferase gene (UF5GT), and PAL, UF3GT and UF5GT
      were reported in P. suffruticosa for the first time. Their expression patterns
      showed that transcription levels of downstream genes in 'Caihui' were basically
      higher than those in 'Xueta', especially PsDFR and PsANS, suggesting that these
      two genes may play a key role in the anthocyanin biosynthesis which resulted in
      the shift from white to red in flowers. These results would provide a better
      understanding of the underlying molecular mechanisms of flower pigmentation in P.
      suffruticosa. 

PMID- 25748575
TI  - An ESRG-interacting protein, COXII, is involved in pro-apoptosis of human
      embryonic stem cells.
AB  - Human embryonic stem cells(hESC) posses very promising application perspective in
      clinical transplant therapies for their characteristics of self-renewal and
      pluripotency. So efforts focusing on the mechanisms of the two characteristics
      are extremely important. ESRG, first identified by our group, is a candidate
      stemness gene of hESC for its much higher expression level in hESC comparing to
      that in 7-day embryoid bodies(EBs). Here, the proteins interacted with ESRG and
      its functions in hESC were explored. Yeast two-hybrid (Y2H) screening system was
      adopted to explore the interacting proteins of ESRG. Then Co-IP was performed to
      confirm the interactions between candidate proteins and ESRG. At last, the
      functions of validated interacting protein were explored by RNA
      interference(RNAi) and Western blot(WB). There were no autonomous activation and
      toxicity in the Y2H system, which verified its availability. Four candidate
      proteins, AAMP, DDT, GNB2L1 and COXII, were discovered, and the interaction
      between ESRG and COXII was ultimately confirmed. The expression of COXII in hESC
      was suppressed by siRNA, and the inhibited mitochondrial apoptosis was observed
      in hESC with downregulated COXII expression. Our work first validated the
      interaction between ESRG and COXII, and demonstrated that COXII serves as a pro
      apoptotic protein in hESC. The results implied that ESRG may play an important
      role in regulating the apoptosis of hESC by interacting with COXII, and thus
      contribute a lot to the maintenance of hESC characteristics. 

PMID- 25748576
TI  - Chloride concentrations in human hepatic cytosol and mitochondria are a function
      of age.
AB  - We recently reported that, in a concentration-dependent manner, chloride protects
      hepatic glutathione transferase zeta 1 from inactivation by dichloroacetate, an
      investigational drug used in treating various acquired and congenital metabolic
      diseases. Despite the importance of chloride ions in normal physiology, and
      decades of study of chloride transport across membranes, the literature lacks
      information on chloride concentrations in animal tissues other than blood. In
      this study we measured chloride concentrations in human liver samples from male
      and female donors aged 1 day to 84 years (n = 97). Because glutathione
      transferase zeta 1 is present in cytosol and, to a lesser extent, in
      mitochondria, we measured chloride in these fractions by high-performance liquid
      chromatography analysis following conversion of the free chloride to
      pentafluorobenzylchloride. We found that chloride concentration decreased with
      age in hepatic cytosol but increased in liver mitochondria. In addition, chloride
      concentrations in cytosol, (105.2 +/- 62.4 mM; range: 24.7-365.7 mM) were
      strikingly higher than those in mitochondria (4.2 +/- 3.8 mM; range 0.9-22.2 mM).
      These results suggest a possible explanation for clinical observations seen in
      patients treated with dichloroacetate, whereby children metabolize the drug more
      rapidly than adults following repeated doses, and also provide information that
      may influence our understanding of normal liver physiology.

PMID- 25748577
TI  - Long-Term Bleb-Related Infections After Trabeculectomy: Incidence, Risk Factors,
      and Influence of Bleb Revision.
AB  - PURPOSE: To report the incidence of late-onset bleb-related infections and to
      identify risk factors for bleb-related infections after trabeculectomy for the
      treatment of glaucoma. DESIGN: Retrospective case series. METHODS: Bleb-related
      infections were defined as blebitis, endophthalmitis, or blebitis with
      endophthalmitis. A total of 1959 eyes of 1423 patients who underwent
      trabeculectomy and who were followed for >=1 year were included. RESULTS: Twenty
      four eyes were diagnosed with bleb-related infections; 15 eyes were found to have
      blebitis and 9 eyes presented with endophthalmitis during the follow-up period of
      5.4 +/- 3.5 years (mean +/- standard deviation). Among 15 eyes with blebitis, 2
      eyes developed endophthalmitis under treatment. The Kaplan-Meier estimated
      incidence of bleb-related infections was 2.0% +/- 0.5% (mean +/- standard error)
      at 10 years. A Cox multivariate analysis showed the significant risk factors for
      a bleb-related infection to be diagnoses of pigmentary glaucoma or juvenile
      glaucoma, history of bleb leak, intraocular pressure sustained below the target
      pressure, chronic blepharitis, and the presence of punctal plugs. Surgical bleb
      revision demonstrated a protective effect against bleb-related infections (P <
      .01) when risk factors were present. CONCLUSIONS: This large case series with
      long-term follow-up demonstrates the incidence of bleb-related infections to be
      less than 2%, and describes the risk factors associated with bleb-related
      infections. A protective effect of surgical bleb revision was demonstrated.
      Clinicians should be constantly vigilant for, and patients made aware of, the
      possibility of bleb-related infections long after trabeculectomy, especially in
      the presence of identified risk factors.

PMID- 25748578
TI  - Intraocular Medulloepitheliomas and Embryonal Tumors With Multilayered Rosettes
      of the Brain: Comparative Roles of LIN28A and C19MC.
AB  - PURPOSE: To compare immunohistochemical and genetic overlaps and differences
      between intraocular medulloepitheliomas and embryonal tumors with multilayered
      rosettes of the brain. DESIGN: Retrospective histopathologic,
      immunohistochemical, and genetic analysis of 20 intraocular medulloepitheliomas.
      METHODS: (1) Review of clinical data and hematoxylin-eosin-stained sections with
      (2) immunohistochemical staining of paraffin sections using a polyclonal antibody
      against the protein LIN28A, and (3) fluorescence in situ hybridization (FISH)
      testing for the amplification of the genetic locus 19q13.42 involving the C19MC
      cluster of miRNA. Ten retinoblastomas served as controls and to determine the
      specificity of these biomarkers for intraocular medulloepitheliomas. RESULTS:
      Nineteen of the 20 intraocular medulloepitheliomas were either diffusely or
      focally LIN28A positive (weak, moderate, or strong). The most intense positivity
      correlated with aggressive behavior such as intraocular tissue invasion or
      extraocular extension. None of the cases studied by FISH harbored an amplicon for
      C19MC. The 10 retinoblastomas were LIN28A and C19MC negative. CONCLUSION: LIN28A
      has a putative role in oncogenesis and is found only in embryonic cells and
      malignancies. Intraocular medulloepitheliomas and embryonal tumors with
      multilayered rosettes of the brain both display LIN28A positivity. Only the
      latter, however, display amplification of the 19q13.42 locus involving C19MC,
      implying that other causative factors are at play in intraocular
      medulloepitheliomas. More aggressive tumor behavior within the eye can be
      partially predicted by LIN28A staining intensity.

PMID- 25748579
TI  - In Vivo confocal microscopic changes of the corneal epithelium and stroma in
      patients with herpes zoster ophthalmicus.
AB  - PURPOSE: To analyze the density and morphology of corneal epithelial cells and
      keratocytes by in vivo confocal microscopy (IVCM) in patients with herpes zoster
      ophthalmicus (HZO) as associated with corneal innervation. DESIGN: Prospective,
      controlled and masked cross-sectional study. METHODS: setting: Single-center
      study. PATIENTS: Thirty eyes with the diagnosis HZO and their contralateral
      clinically unaffected eyes, 15 eyes of 15 normal controls. intervention
      procedures: In vivo confocal microscopy and corneal esthesiometry of the central
      cornea. MAIN OUTCOME MEASURES: Changes in morphology and density of the
      superficial and basal epithelial cells and stromal keratocytes, and correlation
      with corneal sensation. RESULTS: The density of superficial epithelial cells in
      HZO eyes with severe sensation loss (766.5 +/- 25.2 cells/mm(2)) was
      significantly lower than both healthy control eyes (1450.23 +/- 150.83
      cells/mm(2)) and contralateral unaffected eyes (1974.13 +/- 298.24 cells/mm(2))
      (P = .003). Superficial epithelial cell size (1162.5 MUm(2)) was significantly
      larger in HZO eyes with severe loss of sensation, as compared to contralateral
      (441.46 +/- 298.14) or healthy eyes (407.4 +/- 47.2MUm(2); all P < .05). The
      density of basal epithelial cells, anterior keratocytes, and posterior
      keratocytes did not show statistical significance between patients, controls, and
      contralateral unaffected eyes. Changes in superficial epithelial cell density and
      morphology correlated strongly with corneal sensation. CONCLUSIONS: In vivo
      confocal microscopy reveals profound HZO-induced changes in the superficial
      epithelium, as demonstrated by increase in cell size, decrease in cell density,
      and squamous metaplasia. We demonstrate that these changes strongly correlate
      with changes in corneal innervation in eyes affected by HZO.

PMID- 25748581
TI  - Active tuning of all-dielectric metasurfaces.
AB  - All-dielectric metasurfaces provide a powerful platform for highly efficient flat
      optical devices, owing to their strong electric and magnetic dipolar response
      accompanied by negligible losses at near-infrared frequencies. Here we
      experimentally demonstrate dynamic tuning of electric and magnetic resonances in
      all-dielectric silicon nanodisk metasurfaces in the telecom spectral range based
      on the temperature-dependent refractive-index change of a nematic liquid crystal.
      We achieve a maximum resonance tuning range of 40 nm and a pronounced change in
      the transmittance intensity up to a factor of 5. Strongly different tuning rates
      are observed for the electric and the magnetic response, which allows for
      dynamically adjusting the spectral mode separation. Furthermore, we
      experimentally investigate the influence of the anisotropic (temperature
      dependent) dielectric environment provided by the liquid crystal on both the
      electric and magnetic resonances. We demonstrate that the phase transition of the
      liquid crystal from its nematic to its isotropic phase can be used to break the
      symmetry of the optical metasurface response. As such, our approach allows for
      spectral tuning of electric and magnetic resonances of all-dielectric
      metasurfaces as well as switching of the anisotropy of the optical response of
      the device. 

PMID- 25748580
TI  - Cognitive behavioral therapy and tai chi reverse cellular and genomic markers of
      inflammation in late-life insomnia: a randomized controlled trial.
AB  - BACKGROUND: Sleep disturbance is associated with activation of systemic and
      cellular inflammation, as well as proinflammatory transcriptional profiles in
      circulating leukocytes. Whether treatments that target insomnia-related
      complaints might reverse these markers of inflammation in older adults with
      insomnia is not known. METHODS: In this randomized trial, 123 older adults with
      insomnia were randomly assigned to cognitive-behavioral therapy for insomnia (CBT
      I), tai chi chih (TCC), or sleep seminar education active control condition for 2
      hour sessions weekly over 4 months with follow-up at 7 and 16 months. We measured
      C-reactive protein (CRP) at baseline and months 4 and 16; toll-like receptor-4
      activated monocyte production of proinflammatory cytokines at baseline and months
      2, 4, 7, and 16; and genome-wide transcriptional profiling at baseline and month
      4. RESULTS: As compared with sleep seminar education active control condition,
      CBT-I reduced levels of CRP (months 4 and 16, ps < .05), monocyte production of
      proinflammatory cytokines (month 2 only, p < .05), and proinflammatory gene
      expression (month 4, p < .01). TCC marginally reduced CRP (month 4, p = .06) and
      significantly reduced monocyte production of proinflammatory cytokines (months 2,
      4, 7, and 16; all ps < .05) and proinflammatory gene expression (month 4, p <
      .001). In CBT-I and TCC, TELiS promoter-based bioinformatics analyses indicated
      reduced activity of nuclear factor-kappaB and AP-1. CONCLUSIONS: Among older
      adults with insomnia, CBT-I reduced systemic inflammation, TCC reduced cellular
      inflammatory responses, and both treatments reduced expression of genes encoding
      proinflammatory mediators. The findings provide an evidence-based molecular
      framework to understand the potential salutary effects of insomnia treatment on
      inflammation, with implications for inflammatory disease risk.

PMID- 25748583
TI  - Field observation of morpho-dynamic processes during storms at a Pacific beach,
      Japan: role of long-period waves in storm-induced berm erosion.
AB  - Many ultrasonic wave gages were placed with a small spacing across the swash zone
      to monitor either sand level or water level. Continuous monitoring conducted for
      a few years enabled the collection of data on the change in wave properties as
      well as swash-zone profiles. Data sets including two cases of large-scale berm
      erosion were analyzed. The results showed that 1) shoreline erosion started when
      high waves with significant power in long-period (1 to 2 min.) waves reached the
      top of a well-developed berm with the help of rising tide; 2) the beach in the
      swash zone was eroded with higher elevation being more depressed, while the
      bottom elevation just outside the swash zone remained almost unchanged; and 3)
      erosion stopped in a few hours after the berm was completely eroded or the swash
      zone slope became uniformly mild. These findings strongly suggest that long waves
      play a dominant role in the swash-zone dynamics associated with these erosional
      events. 

PMID- 25748584
TI  - Contribution of eNOS variants to the genetic susceptibility of coronary artery
      disease in a Tunisian population.
AB  - Nitric oxide (NO), produced by the enzyme endothelial nitric oxide synthase
      (eNOS), has critical roles in the regulation of vascular homeostasis and
      prevention of atherogenesis by inhibiting leukocytes, platelet activation, and
      smooth muscle cell proliferation. There is strong experimental and clinical
      evidence that abnormalities in eNOS availability play an important role in the
      pathophysiology of coronary artery disease (CAD). Controversial results regarding
      the association of eNOS gene polymorphisms with CAD have been reported. The aim
      of this study is to investigate the relationship of the 894G>T (rs1799983) and
      4a/4b (rs61722009) polymorphisms of the eNOS gene with the presence of CAD in the
      Tunisian population. A total of 332 patients with CAD and 368 controls were
      included in this study. The 894G>T (rs1799983) single-nucleotide polymorphisms
      were analyzed by polymerase chain reaction-restriction fragment length
      polymorphism, and 4a/4b (rs61722009) polymorphism just by polymerase chain
      reaction (PCR). eNOS rs1799983 was significantly associated with CAD under the
      additive, dominant, but not recessive, models (additive model OR: 2.81; 95% CI
      [2.05-3.85]; p<0.001, dominant model OR: 2.84; 95% CI [2.09-3.86]; p<0.001, and
      recessive models p=0.09). This remained significant after adjustment for age,
      gender, diabetes, smoking, and hypertension. In contrast to eNOS rs1799983, eNOS
      rs61722009 was not associated with CAD under any of the genetic models tested.
      These findings suggest that the G894T (rs1799983) polymorphism of the eNOS gene
      was associated with CAD in Tunisian patients. 

PMID- 25748582
TI  - Gene regulatory systems that control gene expression in the Ciona embryo.
AB  - Transcriptional control of gene expression is one of the most important
      regulatory systems in animal development. Specific gene expression is basically
      determined by combinatorial regulation mediated by multiple sequence-specific
      transcription factors. The decoding of animal genomes has provided an opportunity
      for us to systematically examine gene regulatory networks consisting of
      successive layers of control of gene expression. It remains to be determined to
      what extent combinatorial regulation encoded in gene regulatory networks can
      explain spatial and temporal gene-expression patterns. The ascidian Ciona
      intestinalis is one of the animals in which the gene regulatory network has been
      most extensively studied. In this species, most specific gene expression patterns
      in the embryo can be explained by combinations of upstream regulatory genes
      encoding transcription factors and signaling molecules. Systematic scrutiny of
      gene expression patterns and regulatory interactions at the cellular resolution
      have revealed incomplete parts of the network elucidated so far, and have
      identified novel regulatory genes and novel regulatory mechanisms. 

PMID- 25748585
TI  - Can an adipofascial flap be used to prevent adhesions after plating of the
      proximal phalanx? A case report.
AB  - Tendon adhesions in zone IV after proximal phalangeal fractures are common and
      may lead to loss of range of motion at the proximal interphalangeal joint. The
      type of fracture, surgical technique and rehabilitation strategy also influence
      the final functional outcome. Plate fixation is a reliable solution in cases of
      comminuted phalangeal fracture. This article describes how adhesions between the
      plate and extensor apparatus in cases of comminuted fractures of the proximal
      phalanx can be reduced by using an adipofascial flap.

PMID- 25748586
TI  - A rare coronal fracture of the medial carpal column: Case report.
AB  - Carpal coronal fractures are rare. We report the case of a 15 year-old male who
      fell from a balcony and suffered a displaced coronal fracture of the capitate,
      hamate and triquetrum. The diagnosis, which was initially made based on the X
      rays, was confirmed by CT scan. Open reduction and internal fixation using
      Herbert screws was performed. To the best of our knowledge, this is the first
      published case of a coronal fracture of these three bones. The patient returned
      to normal activities after six months.

PMID- 25748587
TI  - Structural, optical, dielectric and antibacterial studies of Mn doped
      Zn0.96Cu0.04O nanoparticles.
AB  - Zn(0.96-x)Cu0.04Mn(x)O (0?x?0.04) nanoparticles were synthesized by sol-gel
      method. The X-ray diffraction pattern indicated that doping of Mn and Cu did not
      change the ZnO hexagonal wurtzite structure. The Mn doped nanoparticles had
      smaller average crystallite size than un-doped Zn0.96Cu0.04O nanoparticles due to
      the distortion in the host ZnO lattice. This distortion prevented the subsequent
      growth and hence the size reduced by Mn doping. The changes in lattice
      parameters, average crystallite size, peak position and peak intensity confirmed
      the Mn substitution in Zn-Cu-O lattice. The Mn and Cu co-doping increased the
      charge carrier density in ZnO nanoparticles which led to increase the dielectric
      constant. The dielectric constant also varied by depend the size of the
      nanoparticles. The change in morphology by Mn-doping was studied by transmission
      electron microscope. The optical absorption and band gap were changed with
      respect to both compositional and size effects. The band gap was initially
      increased from 3.65 to 3.73 eV at 1% of Mn doping, while decreasing trend in band
      gap was noticed for further increase of Mn. The band gap was decreased from 3.73
      to 3.48 eV when Mn concentration was increased from 2% to 4%. Presence of
      chemical bonding and purity of the nanoparticles were confirmed by FTIR spectra.
      The antibacterial study revealed that that the antibacterial activity of
      Zn0.96Cu0.04O is enhanced by Mn doping.

PMID- 25748588
TI  - Crystal growth, morphology, spectrographic characterization and thermal
      properties of Glycine Barium Bromo Chloride crystals.
AB  - Glycine Barium Bromo Chloride material was purified by repeated
      recrystallization. Single crystal was grown by the slow evaporation solution
      technique (SEST). The presence of functional groups in the grown crystals was
      confirmed by Fourier transform infrared spectrum analysis. Thermal properties of
      the crystals were investigated using thermogravimetric (TG) and differential
      thermal analyses (DTA). The dielectric studies were carried out to identify the
      phase transition temperature and the dielectric constant was found. The
      transparency of crystal was tested using UV-visible spectra. Single crystal X-ray
      diffraction study has been carried out to find the crystal system and unit cell
      parameters. 

PMID- 25748589
TI  - Synthesis, characteristics and antimicrobial activity of ZnO nanoparticles.
AB  - The utilization of various plant resources for the bio synthesis of metallic nano
      particles is called green technology and it does not utilize any harmful
      protocols. Present study focuses on the green synthesis of ZnO nano particles by
      Zinc Carbonate and utilizing the bio-components of powder extract of dry ginger
      rhizome (Zingiber officinale). The ZnO nano crystallites of average size range of
      23-26 nm have been synthesized by rapid, simple and eco friendly method. Zinc
      oxide nano particles were characterized by using X-ray diffraction (XRD),
      Scanning Electron Microscope (SEM), Energy Dispersive X-ray spectroscopy (EDX).
      FTIR spectra confirmed the adsorption of surfactant molecules at the surface of
      ZnO nanoparticles and the presence of ZnO bonding. Antimicrobial activity of ZnO
      nano particles was done by well diffusion method against pathogenic organisms
      like Klebsiella pneumonia, Staphylococcus aureus and Candida albicans and
      Penicillium notatum. It is observed that the ZnO synthesized in the process has
      the efficient antimicrobial activity.

PMID- 25748590
TI  - Synthesis, spectroscopic investigation and computational study of 3-(1
      (((methoxycarbonyl)oxy)imino)ethyl)-2H-chromen-2-one.
AB  - The molecular structure and vibrational modes of 3-acetylcoumarin oxime carbonate
      (abbreviated as 3-ACOC) have been investigated by FT-IR, FT-Raman, NMR spectra
      and also by computational methods using HF and B3LYP with 6-311++G(d,p) basis
      set. The optimized geometric parameters (bond lengths, bond angles and dihedral
      angles) were in good agreement with the corresponding experimental values of 3
      ACOC. The calculated vibrational frequencies of normal modes from DFT method
      matched well with the experimental values. The complete assignments were made on
      the basis of the total energy distribution (TED) of the vibrational modes. NMR
      ((1)H and (13)C) chemical shifts were calculated by GIAO method and the results
      were compared with the experimental values. The other parameters like dipole
      moment, polarizability, first order hyperpolarizability, zero-point vibrational
      energy, E(HOMO), E(LUMO), heat capacity and entropy have also been computed.

PMID- 25748591
TI  - A new multicomponent salt of imidazole and tetrabromoterepthalic acid:
      structural, optical, thermal, electrical transport properties and antibacterial
      activity along with Hirshfeld surface analysis.
AB  - Herein, we report the structural, optical, thermal and electrical transport
      properties of a new multicomponent salt (TBTA(2-)).2(IM(+)).(water) [TBTA-IM] of
      tetrabromoterepthalic acid (TBTA) with imidazole (IM). The crystal structure of
      TBTA-IM is determined by both the single crystal and powder X-ray diffraction
      techniques. The structural analysis has revealed that the supramolecular charge
      assisted O(-)?HN(+) hydrogen bonding and Br?pi interactions play the most vital
      role in formation of this multicomponent supramolecular assembly. The Hirshfeld
      surface analysis has been carried out to investigate supramolecular interactions
      and associated 2D fingerprint plots reveal the relative contribution of these
      interactions in the crystal structure quantitatively. According to theoretical
      analysis the HOMO-LUMO energy gap of the salt is 2.92 eV. The salt has been
      characterized by IR, UV-vis and photoluminescence spectroscopic studies. It shows
      direct optical transition with band gaps of 4.1 eV, which indicates that the salt
      is insulating in nature. The photoluminescence spectrum of the salt is
      significantly different from that of TBTA. Further, a comparative study on the
      antibacterial activity of the salt with respect to imidazole, Gatifloxacin and
      Ciprofloxacin has been performed. Moreover, the current-voltage (I-V)
      characteristic of ITO/TBTA-IM/Al sandwich structure exhibits good rectifying
      property and the electron tunneling process governs the electrical transport
      mechanism of the device.

PMID- 25748592
TI  - A new boronic acid fluorescent sensor based on fluorene for monosaccharides at
      physiological pH.
AB  - Fluorescent boronic acids are very useful fluorescent sensor for detection of
      biologically important saccharides. Herein we synthesized a new fluorene-based
      fluorescent boronic acid that shows significant fluorescence changes upon
      addition of saccharides at physiological pH. Upon addition of fructose, sorbitol,
      glucose, galactose, ribose, and maltose at different concentration to the
      solution of 7-(dimethylamino)-9,9-dimethyl-9H-fluoren-2-yl-2-boronic acid (7
      DMAFBA, 1), significant decreases in fluorescent intensity were observed. It was
      found that this boronic acid has high affinity (K(a)=3582.88 M(-1)) and
      selectivity for fructose over glucose at pH=7.4. The sensor 1 showed a linear
      response toward d-fructose in the concentrations ranging from 2.5*10(-5) to 4*10(
      4) mol L(-1) with the detection limit of 1.3*10(-5) mol L(-1).

PMID- 25748593
TI  - 1-Amino-2-hydroxy-4-naphthalenesulfonic acid based Schiff bases or naphtho[1,2
      d]oxazoles: selective synthesis and photophysical properties.
AB  - A series of Schiff base and naphtho[1,2-d]oxazole derivatives were selectively
      synthesized via condensation reaction of 1-amino-2-hydroxy-4-naphthalenesulfonic
      acid and benzaldehyde derivatives at same conditions. The synthesized compounds
      were then characterized by using (1)HNMR, (13)CNMR, FTIR spectroscopies and
      elemental analyses. It was seen that the Schiff bases generated in the presence
      of OH group at ortho position of benzaldehyde derivatives. However, the products
      were naphtho[1,2-d]oxazoles in other cases. Then, the synthesized compounds were
      photophysically investigated by UV absorption and fluorescence emission
      spectroscopies. As a result, these Schiff bases have shown long wavelength
      absorption (lambda(max): 386 nm) and emission (lambda(max): 429-437 nm) effect
      while synthesized naphtho[1,2-d]oxazole derivatives have a set of absorption
      (lambda(max): about 296, 308, 320 nm) and emission maxima (lambda(max): 378-395
      nm) at lower wavelength.

PMID- 25748594
TI  - Growing evidence for a weighty problem.

PMID- 25748595
TI  - [Advanced care directives in Andalusia, 2004-2014].

PMID- 25748596
TI  - Tourism and recreation listed as a threat for a wide diversity of vascular
      plants: a continental scale review.
AB  - Tourism and recreation are diverse and popular activities. They may also
      contribute to the risk of extinction for some plants because of the range and
      severity of their impacts, including in protected areas: but which species, where
      and how? To evaluate the extent to which tourism and recreation may be
      threatening process for plants, we conducted a continental level review of listed
      threats to endangered vascular plants using data from Australia. Of the 659
      vascular plant species listed as critically endangered or endangered by the
      Australian Government, tourism and recreation were listed as a threat(s) for 42%.
      This is more than those listed as threatened by climate change (26%) and close to
      the proportion listed as threatened by altered fire regimes (47%). There are
      plant species with tourism and recreation listed threats in all States and
      Territories and from all but one bioregion in Australia. Although more than 45
      plant families have species with tourism and recreation listed as threats,
      orchids were the most common species listed as at risk from these threats (90
      species). The most common types of threats listed were visitors collecting plants
      in protected areas (113 species), trampling by hikers and others (84 species),
      damage from recreational vehicles (59 species) and road infrastructure (39
      species). Despite the frequency with which tourism and recreation were listed as
      threats in Australia, research quantifying these threats and methods to
      ameliorate their impacts are still limited. Although this lack of information
      contributes to the challenge of managing tourism and recreation, impacts from
      visitors will often be easier to manage within natural areas than those from
      larger scale threats such as altered fire regimes and climate change. 

PMID- 25748597
TI  - Evaluating localism in the management of post-consumer plastic bottles in
      Honolulu, Hawai'i: perspectives from industrial ecology and political ecology.
AB  - Localism or regionalization has become a popular topic in urban design, but
      recent critics raise the question of whether the local or regional scale is most
      desirable for industrial ecosystems. As a way to explore the claim that localized
      metabolism is more sustainable, this study examines the costs and benefits of two
      differentially scaled strategies for the management of post-consumer polyethylene
      terephthalate (PET) bottles originating in the city of Honolulu, Hawai'i: local
      incineration and trans-continental recycling. We first estimate total
      environmental impacts of two options using life cycle assessment, and then
      disaggregate them into local versus non-local impacts to examine the spatial
      distribution of costs and benefits. We further assess the environmental
      justification for localized waste management in relation to the broader socio
      economic motivations that underlie the way that plastics are managed in Honolulu.
      In doing so we assess the scale at which waste management is optimized from an
      environmental standpoint as well as the non-environmental considerations such as
      security and safety that influence the politics of scale involved in urban
      metabolic design. By illustrating the trade-offs between a local versus global
      metabolic pathway for plastic waste, the results from our Honolulu case study are
      globally relevant for communities interested in sustainable urban design and in
      particular urban waste management. 

PMID- 25748598
TI  - Impact of reduced water consumption on sulfide and methane production in rising
      main sewers.
AB  - Reduced water consumption (RWC), for water conservation purposes, is expected to
      change the wastewater composition and flow conditions in sewer networks and
      affect the in-sewer transformation processes. In this study, the impact of
      reduced water consumption on sulfide and methane production in rising main sewers
      was investigated. Two lab-scale rising main sewer systems fed with wastewater of
      different strength and flow rates were operated to mimic sewers under normal and
      RWC conditions (water consumption reduced by 40%). Sulfide concentration under
      the RWC condition increased by 0.7-8.0 mg-S/L, depending on the time of a day.
      Batch test results showed that the RWC did not change the sulfate-reducing
      activity of sewer biofilms, the increased sulfide production being mainly due to
      longer hydraulic retention time (HRT). pH in the RWC system was about 0.2 units
      lower than that in the normal system, indicating that more sulfide would be in
      molecular form under the RWC condition, which would result in increased sulfide
      emission to the atmosphere as confirmed by the model simulation. Model based
      analysis showed that the cost for chemical dosage for sulfide mitigation would
      increase significantly per unit volume of sewage, although the total cost would
      decrease due to a lower sewage flow. The dissolved methane concentration under
      the RWC condition was over two times higher than that under the normal flow
      condition and the total methane discharge was about 1.5 times higher, which would
      potentially result in higher greenhouse gas emissions. Batch tests showed that
      the methanogenic activity of sewer biofilms increased under the RWC condition,
      which along with the longer HRT, led to increased methane production. 

PMID- 25748599
TI  - The conceptual foundation of environmental decision support.
AB  - Environmental decision support intends to use the best available scientific
      knowledge to help decision makers find and evaluate management alternatives. The
      goal of this process is to achieve the best fulfillment of societal objectives.
      This requires a careful analysis of (i) how scientific knowledge can be
      represented and quantified, (ii) how societal preferences can be described and
      elicited, and (iii) how these concepts can best be used to support communication
      with authorities, politicians, and the public in environmental management. The
      goal of this paper is to discuss key requirements for a conceptual framework to
      address these issues and to suggest how these can best be met. We argue that a
      combination of probability theory and scenario planning with multi-attribute
      utility theory fulfills these requirements, and discuss adaptations and
      extensions of these theories to improve their application for supporting
      environmental decision making. With respect to (i) we suggest the use of
      intersubjective probabilities, if required extended to imprecise probabilities,
      to describe the current state of scientific knowledge. To address (ii), we
      emphasize the importance of value functions, in addition to utilities, to support
      decisions under risk. We discuss the need for testing "non-standard" value
      aggregation techniques, the usefulness of flexibility of value functions
      regarding attribute data availability, the elicitation of value functions for sub
      objectives from experts, and the consideration of uncertainty in value and
      utility elicitation. With respect to (iii), we outline a well-structured
      procedure for transparent environmental decision support that is based on a clear
      separation of scientific prediction and societal valuation. We illustrate aspects
      of the suggested methodology by its application to river management in general
      and with a small, didactical case study on spatial river rehabilitation
      prioritization. 

PMID- 25748600
TI  - L-type calcium channels contribute to 5-HT3-receptor-evoked CaMKIIalpha and ERK
      activation and induction of emesis in the least shrew (Cryptotis parva).
AB  - Activation of serotonergic 5-HT3 receptors by its selective agonist 2-methyl
      serotonin (2-Me-5-HT) induces vomiting, which is sensitive to selective
      antagonists of both 5-HT3 receptors (palonosetron) and L-type calcium channels
      (LTCC) (amlodipine or nifedipine). Previously we demonstrated that 5-HT3 receptor
      activation also causes increases in a palonosetron-sensitive manner in: i)
      intracellular Ca(2+) concentration, ii) attachment of calmodulin (CaM) to 5-HT3
      receptor, and iii) phosphorylation of Ca(2+)/calmodulin-dependent protein kinase
      IIalpha (CaMKIIalpha) and extracellular-signal-regulated kinase 1/2 (ERK1/2).
      Here, we investigate the role of the short-acting LTCC blocker nifedipine on 2-Me
      5-HT-evoked intracellular Ca(2+) increase and on downstream intracellular emetic
      signaling, which have been shown to be coupled with 2-Me-5-HT's emetic effects in
      the least shrew. Using the cell-permeant Ca(2+) indicator fluo-4 AM, here we
      present evidence for the contribution of Ca(2+) influx through LTCCs (sensitive
      to nifedipine) in 2-Me-5-HT (1uM) -evoked rise in cytosolic Ca(2+) levels in
      least shrew brainstem slices. Nifedipine pretreatment (10mg/kg, s.c.) also
      suppressed 2-Me-5-HT-evoked interaction of 5-HT3 receptors with CaM as well as
      phosphorylation of CaMKIIalpha and ERK1/2 in the least shrew brainstem, and 5-HT3
      receptors -CaM colocalization in jejunum of the small intestine. In vitro
      exposure of isolated enterochromaffin cells of the small intestine to 2-Me-5-HT
      (1uM) caused CaMKIIalpha phosphorylation, which was also abrogated by nifedipine
      pretreatment (0.1uM). In addition, pretreatment with the CaMKII inhibitor KN62
      (10mg/kg, i.p.) suppressed emesis and also the activation of CaMKIIalpha, and ERK
      in brainstem caused by 2-Me-5-HT (5mg/kg, i.p.). This study provides further
      mechanistic explanation for our published findings that nifedipine can dose
      dependently protect shrews from 2-Me-5-HT-induced vomiting.

PMID- 25748601
TI  - A step ahead of PPARgamma full agonists to PPARgamma partial agonists:
      therapeutic perspectives in the management of diabetic insulin resistance.
AB  - Described since long as a member of the nuclear receptor superfamily, peroxisome
      proliferator-activated receptors (PPARs) regulate the gene expression of proteins
      involved in glucose and lipid metabolism. PPARs indeed regulate several
      physiologic processes, including lipid homeostasis, adipogenesis, inflammation,
      and wound healing. PPARs bind natural or synthetic PPAR ligands can function as
      cellular sensors to regulate the gene transcription. Dyslipidemia, and type 2
      diabetes mellitus (T2DM) with insulin resistance are treated using agonists of
      PPARalpha and PPARgamma, respectively. The PPARgamma is a key regulator of
      insulin sensitization and glucose metabolism, and therefore is considered as an
      imperative pharmacological target to combat diabetic metabolic disease and
      insulin resistance. Of note, currently available PPARgamma full agonists like
      rosiglitazone display serious adverse effects such as fluid retention/oedema,
      weight gain, and increased incidence of cardiovascular events. On the other hand,
      PPARgamma partial agonists are being suggested to devoid or having less incidence
      of these undesirable events, and are under developmental stages. Current research
      is on the way for the development of novel PPARgamma partial agonists with
      enhanced therapeutic efficacy and reduced adverse effects. This review sheds
      lights on the current status of development of PPARgamma partial agonists, for
      the management of T2DM, having comparatively less or no adverse effects to that
      of PPARgamma full agonists.

PMID- 25748602
TI  - Tingenone, a pentacyclic triterpene, induces peripheral antinociception due to
      NO/cGMP and ATP-sensitive K(+) channels pathway activation in mice.
AB  - Substances derived from plants play an important role in the development of new
      analgesic drugs, among them, triterpenoids. The connection between the
      participation of L-arginine/NO/cGMP pathway and the activation of ATP-sensitive
      K(+) channels (KATP) has been established on the peripheral antinociception
      induced by various drugs. The study assessed the involvement of L
      arginine/NO/cGMP/KATP pathway in the antinociceptive effect induced by tingenone,
      from Maytenus imbricata, against the hyperalgesia evoked by prostaglandin E2
      (PGE2) in peripheral pathway. The paw pressure test was used, with hyperalgesia
      induced by intraplantar injection of PGE2 (2 MUg). Tingenone (200 ug/paw)
      administered into the right hind paw induced a local antinociceptive effect, that
      was antagonized by l-NOArg, nonselective nitric oxide synthase (NOS) inhibitor
      and by L-NPA, selective neuronal NOS (nNOS) inhibitor. The L-NIO, selective
      inhibitor of endothelial (eNOS), and the L-NIL, selective inhibitor of inducible
      (iNOS), did not alter the peripheral antinociceptive effect of the tingenone. The
      ODQ, selective soluble guanylyl cyclase inhibitor, prevented the antinociceptive
      effect of tingenone, and zaprinast, inhibitor of the phosphodiesterase that is
      cyclic guanosine monophosphate (cGMP) specific, intensified the peripheral
      antinociceptive effect of the smaller dose of tingenone. Glibenclamide, ATP
      sensitive K(+) channels (KATP) blocker, but not tetraethylammonium chloride,
      voltage-dependent K(+) channel blocker; dequalinium dichloride, blocker of the
      small conductance Ca(2+)-activated K(+) channel, and paxilline, a potent blocker
      of high-conductance Ca(2+)-activated K(+) channels, respectively, prevented the
      peripheral antinociceptive effect of tingenone. The results demonstrate that
      tingenone induced a peripheral antinociceptive effect by L-arginine/NO/cGMP/KATP
      pathway activation, with potential for a new analgesic drug.

PMID- 25748603
TI  - Electronic case management with homeless youth.
AB  - Case management, a widely practiced form of service brokerage, is associated with
      a variety of positive outcomes for homeless youth, but it may be difficult to
      implement, as youth face logistical barriers to attending in-person meetings. As
      part of a larger clinical trial, the current study investigates the feasibility
      of providing electronic case management (ECM) to homeless youth, using cell
      phones, texts, email, and Facebook. Youth were given prepaid cell-phones and a
      case manager who provided four ECM sessions every 2-3 weeks over a 3-month
      period. Contact logs were used to record how many youth engaged in ECM, how many
      attempts were necessary to elicit engagement, and youths' preferred technology
      methods for engaging. Although engagement in the number of ECM sessions varied,
      the majority of youth (87.5%) engaged in at least one ECM session. Youth (41%)
      most commonly needed one contact before they engaged in an ECM session, and the
      majority responded by the third attempt. While youth most commonly answered calls
      directly, their chosen method of returning calls was texting. The majority of
      youth (80%) described ECM positively, reporting themes of convenience,
      connection, and accountability. The use of ECM, particularly of texting, offers
      promising implications for providing services to homeless youth. 

PMID- 25748604
TI  - Routine outcome measurement in mental health service consumers: who should
      provide support for the self-assessments?
AB  - This study examined whether mental health community service users completed
      outcome self-reports differently when assessments were supervised by internal vs.
      external staff. The examination of potential differences between the two has
      useful implications for mental health systems that take upon themselves the
      challenge of Routine Outcome Measurement (ROM), as it might impact allocation of
      public resources and managed care program planning. 73 consumers completed the
      Manchester Short Assessment of Quality of Life (MANSA), a shortened version of
      the Recovery Assessment Scale (RAS), and a functioning questionnaire.
      Questionnaires were administered, once using support provided by internal staff
      and once using support provided by external professional staff, with a one-month
      time interval and in random order. A MANOVA Repeated Measures showed no
      differences in outcomes of quality of life and recovery between internal and
      external support. Functioning scores were higher for the internal support when
      the internal assessments were performed first. Overall, except for the
      differences in functioning assessment, outcome scores were not determined by the
      supporting agency. This might indicate that when measuring quality of life and
      recovery, different supporting methods can be used to gather outcome measures and
      internal staff might be a good default agency to do this. Differences found in
      functioning assessment are discussed. 

PMID- 25748606
TI  - Reduction of insulinotropic properties of GLP-1 and GIP after glucocorticoid
      induced insulin resistance.
AB  - AIMS/HYPOTHESIS: We evaluated the insulinotropic properties of glucagon-like
      peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) in
      healthy individuals at risk of developing type 2 diabetes before and after
      glucocorticoid-induced insulin resistance. METHODS: Nineteen healthy, glucose
      tolerant, first-degree relatives of type 2 diabetic patients underwent OGTT and 7
      mmol/l and 15 mmol/l glucose clamps with concomitant infusions of GLP-1, GIP or
      NaCl and a final infusion of arginine for determination of maximum beta cell
      capacity before and after treatment with dexamethasone. In addition, first-phase
      insulin responses were determined at 7 mmol/l and 15 mmol/l and second-phase
      insulin responses at 7 mmol/l. RESULTS: After dexamethasone treatment, all 19
      participants had increased insulin resistance (HOMA-IR and insulin sensitivity
      index [M/I] values) and 2 h plasma glucose concentrations, while beta cell
      function indices generally increased according to the increased resistance. First
      phase insulin responses induced by GLP-1 and GIP at 7 mmol/l and maximal beta
      cell secretory capacity did not differ before and after dexamethasone, while
      second-phase responses to 7 mmol/l and first-phase responses to 15 mmol/l glucose
      were reduced equally for both hormones. CONCLUSIONS/INTERPRETATION:
      Glucocorticoid-induced insulin resistance in individuals at risk of type 2
      diabetes leads to a reduced insulinotropic effect of the incretin hormones. This
      reduction was not associated with a decrease in the maximal beta cell secretory
      capacity, indicating that the reduced incretin effect in the developing
      dysglycaemia of the present experimental model is due to a specific early
      reduction of the insulinotropic effects of the incretin hormones. TRIAL
      REGISTRATION: Clinicaltrials.gov NCT02235584.

PMID- 25748607
TI  - Di(2-ethylhexyl) phthalate inhibits B cell proliferation and reduces the
      abundance of IgM-secreting cells in cultured immune tissues of the rainbow trout.
AB  - Plasticizer di(2-ethylhexyl) phthalate (DEHP) and its active metabolite MEHP have
      important immunotoxic effects in mammalian species, including inhibition of cell
      proliferation, inflammation inhibition, lowering of the antibody response, and
      apoptosis. Virtually nothing is known about the potential detrimental effects of
      DEHP/MEHP on the teleost immune system, although phthalates are a likely threat
      to fish health. Here we investigated whether short-term in vitro DEHP exposure
      would affect B lineage cells in the rainbow trout, using cultured immune tissues.
      Cell culture conditions, evidence of cellular incorporation of DEHP, and possible
      effects of DEHP on immune genes were first established using the mouse pre-B cell
      line PD31 and data confirmed a dose-dependent cellular uptake of DEHP using
      liquid chromatography-coupled ion trap mass spectrometry. Effects of in vitro
      DEHP exposure on trout B cell proliferation were tested by flow cytometry.
      Significant, dose-dependent inhibition was evident in both anterior and posterior
      kidney cultures after 24 h exposure to >=4 MUM DEHP. DEHP-induced cell death was
      not significant for the range of DEHP tested. Further, the abundance of IgM
      secreting plasmablasts and plasma cells was significantly reduced after in vitro
      exposure of >=16 MUM DEHP for 2 or 7 days. Finally, in vitro DEHP exposure
      significantly lowered the levels of secreted HCmu transcripts in a dose-dependent
      manner. B lineage cells from posterior kidney were more sensitive to effects of
      in vitro DEHP exposure than those from anterior kidney. Together, the data
      support a model where DEHP modifies the normal B cell activation pathways in
      rainbow trout, promoting B cell differentiation while suppressing plasmablast
      expansion, resulting in fewer IgM-secreting plasma cells. Insufficient production
      of protective antibody make fish more susceptible to infection, and increases
      their risk for disease and mortality in polluted waters.

PMID- 25748605
TI  - The drosophila T-box transcription factor midline functions within Insulin/Akt
      and c-Jun-N terminal kinase stress-reactive signaling pathways to regulate
      interommatial bristle formation and cell survival.
AB  - We recently reported that the T-box transcription factor midline (mid) functions
      within the Notch-Delta signaling pathway to specify sensory organ precursor (SOP)
      cell fates in early-staged pupal eye imaginal discs and to suppress apoptosis
      (Das et al.). From genetic and allelic modifier screens, we now report that mid
      interacts with genes downstream of the insulin receptor(InR)/Akt, c-Jun-N
      terminal kinase (JNK) and Notch signaling pathways to regulate interommatidial
      bristle (IOB) formation and cell survival. One of the most significant mid
      interacting genes identified from the modifier screen is dFOXO, a transcription
      factor exhibiting a nucleocytoplasmic subcellular distribution pattern. In common
      with dFOXO, we show that Mid exhibits a nucleocytoplasmic distribution pattern
      within WT third-instar larval (3(o)L) tissue homogenates. Because dFOXO is a
      stress-responsive factor, we assayed the effects of either oxidative or metabolic
      stress responses on modifying the mid mutant phenotype which is characterized by
      a 50% loss of IOBs within the adult compound eye. While metabolic starvation
      stress does not affect the mid mutant phenotype, either 1 mM paraquat or 20%
      coconut oil, oxidative stress inducers, partially suppresses the mid mutant
      phenotype resulting in a significant recovery of IOBs. Another significant mid
      interacting gene we identified is groucho (gro). Mid and Gro are predicted to act
      as corepressors of the enhancer-of-split gene complex downstream of Notch.
      Immunolabeling WT and dFOXO null 3(o)L eye-antennal imaginal discs with anti-Mid
      and anti-Engrailed (En) antibodies indicate that dFOXO is required to activate
      Mid and En expression within photoreceptor neurons of the eye disc. Taken
      together, these studies show that Mid and dFOXO serve as critical effectors of
      cell fate specification and survival within integrated Notch, InR/dAkt, and JNK
      signaling pathways during 3(o)L and pupal eye imaginal disc development. 

PMID- 25748608
TI  - Systemic model of chronic benzodiazepine use among mature adults.
AB  - OBJECTIVES: Our goal was to build a systemic model of chronic use among community
      dwelling mature benzodiazepine (BZD) users. BZDs are commonly prescribed for
      symptoms of anxiety and/or insomnia despite their documented side effects over
      time. METHOD: We conducted in-depth interviews with 23 mature (50 years and over)
      users, 14 women and 9 men, as well as 9 general practitioners and 11 pharmacists.
      We chose the grounded theory approach for our analysis. RESULTS: Results yielded
      a systemic model of chronic BZD use, illustrating onset and maintenance of use,
      and taking into account individual life context, intervening conditions (e.g.
      family and doctor--patient interactions) and structural factors (medicalization,
      ageism, influence of the media and pharmaceutical industry, etc.). Based on our
      findings, we suggest that intervention should go beyond medical issues and extend
      to the individual's perception of aging in the modern society, as well as
      attitudes of families and health professionals regarding long-term BZD use.
      Family members should be involved in the weaning process and adoption of new life
      habits. General practitioners should be better trained regarding geriatric
      psychosocial issues and offer alternatives to prescribe psychotropic drugs such
      as cognitive behavior therapy for insomnia. Also, as a society, we should
      reconsider the highly medicalized stance we take to compensate for age-related
      losses. The influential role of the pharmaceutical industry in the process is
      discussed. CONCLUSION: We conclude that a predominantly biomedical perspective on
      human development diminishes patient-centered care within a socially
      contextualized, individual perspective.

PMID- 25748609
TI  - Effect of alveolar bone support on zygomatic implants in an extra-sinus position-
      a finite element analysis study.
AB  - The objective was to investigate the influence of maxillary alveolar bone on the
      stress distribution of zygomatic implants in an extra-sinus position. A three
      dimensional finite element model was created based on a computed tomography scan
      of an edentulous female patient. Two zygomatic implants were modelled and placed
      in the skull in an extra-sinus position. These were supported by the zygomatic
      bone and the maxillary alveolar bone and were connected by a fixed bridge. This
      model was duplicated, and the area of the maxillary alveolar bone supporting the
      implants was removed. Occlusal and lateral forces were applied to both models and
      the maximum von Mises stresses were recorded. Higher maximum stresses were noted
      in the model with no alveolar support. Occlusal stresses were higher than lateral
      stresses in the model with no alveolar support, while occlusal stresses were
      lower than lateral stresses in the model with alveolar support. Low stresses were
      noted in the zygomatic bone in both models. Maxillary alveolar bone support is
      beneficial in the distribution of forces for zygomatic implants placed in an
      extra-sinus position.

PMID- 25748610
TI  - Setbacks of transoral temporomandibular joint ankylotic mass excision.

PMID- 25748611
TI  - Trunk-pelvis motion, joint loads, and muscle forces during walking with a
      transtibial amputation.
AB  - People with unilateral, transtibial amputation (TTA) have an increased prevalence
      of chronic low back pain (LBP) relative to able-bodied people. However, a
      definitive cause of increased LBP susceptibility has not been determined. The
      purpose of this work was to compare dynamic trunk-pelvis biomechanics between
      people with (n=6) and without (n=6) unilateral TTA during walking using a
      computational modeling approach. A generic, muscle-actuated whole body model was
      scaled to each participant, and experimental walking data were used in a static
      optimization framework to calculate trunk-pelvis motion, L4L5 joint contact
      forces, and muscle forces within the trunk-pelvis region. Results included
      several significant between-group differences in trunk-pelvis biomechanics during
      different phases of the gait cycle. Most significant was greater lateral bending
      toward the residual side during residual single-limb stance (p<0.01), concurrent
      with an elevated L4L5 joint contact force (p=0.02) and greater muscle force from
      the intact-side obliques (p<0.01) in people with TTA relative to able-bodied
      people. During both double-limb support phases, people with TTA also had a
      greater range of axial trunk rotation away from the leading limb, concurrent with
      greater ranges of muscle forces in the erector spinae and obliques. In addition,
      a greater range of force (p=0.03) in residual-side psoas was found during early
      residual limb swing in people with TTA. Repeated exposure to atypical motion and
      joint/muscle loading in people with TTA may contribute to the development of
      secondary musculoskeletal disorders, including chronic, mechanical LBP. 

PMID- 25748613
TI  - Statin treatment: can genetics sharpen the focus?

PMID- 25748612
TI  - Genetic risk, coronary heart disease events, and the clinical benefit of statin
      therapy: an analysis of primary and secondary prevention trials.
AB  - BACKGROUND: Genetic variants have been associated with the risk of coronary heart
      disease. In this study, we tested whether or not a composite of these variants
      could ascertain the risk of both incident and recurrent coronary heart disease
      events and identify those individuals who derive greater clinical benefit from
      statin therapy. METHODS: A community-based cohort study (the Malmo Diet and
      Cancer Study) and four randomised controlled trials of both primary prevention
      (JUPITER and ASCOT) and secondary prevention (CARE and PROVE IT-TIMI 22) with
      statin therapy, comprising a total of 48,421 individuals and 3477 events, were
      included in these analyses. We studied the association of a genetic risk score
      based on 27 genetic variants with incident or recurrent coronary heart disease,
      adjusting for traditional clinical risk factors. We then investigated the
      relative and absolute risk reductions in coronary heart disease events with
      statin therapy stratified by genetic risk. We combined data from the different
      studies using a meta-analysis. FINDINGS: When individuals were divided into low
      (quintile 1), intermediate (quintiles 2-4), and high (quintile 5) genetic risk
      categories, a significant gradient in risk for incident or recurrent coronary
      heart disease was shown. Compared with the low genetic risk category, the
      multivariable-adjusted hazard ratio for coronary heart disease for the
      intermediate genetic risk category was 1.34 (95% CI 1.22-1.47, p<0.0001) and that
      for the high genetic risk category was 1.72 (1.55-1.92, p<0.0001). In terms of
      the benefit of statin therapy in the four randomised trials, we noted a
      significant gradient (p=0.0277) of increasing relative risk reductions across the
      low (13%), intermediate (29%), and high (48%) genetic risk categories. Similarly,
      we noted greater absolute risk reductions in those individuals in higher genetic
      risk categories (p=0.0101), resulting in a roughly threefold decrease in the
      number needed to treat to prevent one coronary heart disease event in the primary
      prevention trials. Specifically, in the primary prevention trials, the number
      needed to treat to prevent one such event in 10 years was 66 in people at low
      genetic risk, 42 in those at intermediate genetic risk, and 25 in those at high
      genetic risk in JUPITER, and 57, 47, and 20, respectively, in ASCOT.
      INTERPRETATION: A genetic risk score identified individuals at increased risk for
      both incident and recurrent coronary heart disease events. People with the
      highest burden of genetic risk derived the largest relative and absolute clinical
      benefit from statin therapy. FUNDING: National Institutes of Health.

PMID- 25748614
TI  - Syrian refugee crisis: when aid is not enough.

PMID- 25748615
TI  - Osteoarthritis.
AB  - Osteoarthritis is a major source of pain, disability, and socioeconomic cost
      worldwide. The epidemiology of the disorder is complex and multifactorial, with
      genetic, biological, and biomechanical components. Aetiological factors are also
      joint specific. Joint replacement is an effective treatment for symptomatic end
      stage disease, although functional outcomes can be poor and the lifespan of
      prostheses is limited. Consequently, the focus is shifting to disease prevention
      and the treatment of early osteoarthritis. This task is challenging since
      conventional imaging techniques can detect only quite advanced disease and the
      relation between pain and structural degeneration is not close. Nevertheless,
      advances in both imaging and biochemical markers offer potential for diagnosis
      and as outcome measures for new treatments. Joint-preserving interventions under
      development include lifestyle modification and pharmaceutical and surgical
      modalities. Some show potential, but at present few have proven ability to arrest
      or delay disease progression. 

PMID- 25748616
TI  - 4 years of the humanitarian tragedy in Syria: who cares?

PMID- 25748617
TI  - Anti-oxidative and anti-inflammatory effects of lipoic acid in rat liver.
AB  - INTRODUCTION: Lipopolysaccharide (LPS) is a key inflammatory component of Gram
      negative bacteria, which after entering the systemic circulation contributes to
      the development of septic hepatic failure. AIM: The aim of this study was to
      evaluate the effects of alpha lipoic acid (LA) on oxidative stress parameters and
      inflammation in endotoxemic rat liver. MATERIAL/METHODS: Male Wistar rats were
      divided into 4 groups, each group consisting of 8 animals. Group I received
      saline and served as a control, Group II received a single dose of LA (60 mg/kg
      i.v.), Group III received lipopolysaccharide (LPS) (15 mg/kg i.v.), and Group IV
      received LPS (15 mg/kg i.v.) and 30 min later received LA (60 mg/kg i.v.). Five
      hours after LPS or LA administration, the animals were sacrificed and the liver
      was isolated for measurements of levels of thiobarbituric acid reactive
      substances (TBARS), hydrogen peroxide (H2O2), total sulfhydryl groups (-SH),
      total glutathione (tGSH) and reduced glutathione (GSH). RESULTS: Injection of LPS
      caused a significant increase in liver TBARS and H2O2 levels and a significant
      decrease in levels of -SH groups, tGSH and GSH. LPS-treated rats also showed an
      increase in TNF-alpha and IL-6 levels and edema in the liver. The administration
      of LA to endotoxemic rats significantly reduced TBARS, H2O2, TNF-alpha, and IL-6
      levels and reduced edema in the liver when compared to the LPS group. This
      antioxidant also resulted in an increase in -SH groups and tGSH and GSH levels
      and ameliorated the glutathione redox status when compared to the LPS group.
      CONCLUSIONS: The results indicated that LA administered 30 min following LPS
      infusion may effectively prevent oxidative stress and inflammation in the liver.
      Thus LA is a potent antioxidant that can be useful in rebuilding LPS-induced
      damaged liver tissue.

PMID- 25748618
TI  - Lung surgery for metastatic epithelial tumours.
AB  - INTRODUCTION: The aim of this study is to evaluate outcomes following the
      surgical treatment of pulmonary metastases in patients with different types of
      epithelial cancers, as well as to identify prognostic factors after
      metastasectomy. MATERIAL/METHODS: We retrospectively reviewed data for 61
      patients who underwent 76 curative resections of pulmonary metastases from
      epithelial tumours during 1997-2002 at our department. Potential prognostic
      factors affecting survival after lung metastasectomy were analysed: disease-free
      interval (DFI), gender, age, the size and number of metastases, mono- or
      bilateral tumour, number of operations and the extent of pulmonary resection.
      RESULTS: The median survival was 36 months. Three factors were identified as
      prognostic for survival after metastasectomy: DFI<24 (p=0.0045), unilateral
      pulmonary metastases (p=0.0062) and no more than one operation (p=0.0065).
      CONCLUSIONS: We concluded that: i) Resection of epithelial pulmonary metastases
      may offer a significant survival benefit for selected patients. ii) Good surgical
      candidates for pulmonary resection are those with a disease-free interval greater
      than 24 months. iii) The total number of thoracotomies, and metastases confined
      to one lung are factors defining patients who experience a better outcome after
      surgery. iv) Lung metastasectomy by conventional surgery is a safe procedure with
      low perioperative morbidity and mortality rates.

PMID- 25748619
TI  - [Long-term use of estrogens: benefit or risk].
AB  - Estrogens are widely used in hormone replacement therapy, gynecology,
      urogynecology and rarely in dermatology. Non-therapeutic use of estrogens is very
      widespread. Estrogens are used as contraceptives, which cause a lot of serious
      side effects. A common clinical problem is skin hyperpigmentation (melasma),
      occurring mainly in women who take contraceptives with high doses of estrogens.
      But low doses of estrogens may also cause skin side effects. The mechanism of
      melasma development is very complicated and not fully understood. It is very
      likely that UV radiation and genetic background can affect melasma development.
      Effective therapy should lead to prevention or alleviation of relapses. Treatment
      should also reduce the area of lesions and improve the appearance of skin. There
      is no effective and universal pattern of treatment, in which only one substance
      or method is used. A combination of different methods is used to optimize the
      therapy. An important role is attributed to prevention, especially protection
      from UV radiation. 

PMID- 25748620
TI  - The use of biodegradable polymers in design of cellular scaffolds.
AB  - The objective of this work was to demonstrate the usage of biodegradable
      polymers, made of calcium alginate and dibutyrylchitin, in the design of cellular
      scaffolds having broad application in reconstructive therapy (dentistry,
      orthopedics). To visualize cells seeded on calcium alginate and dibutyrylchitin
      polymers DAPI staining of fibroblasts nuclei was used. The cytotoxicity of the
      materials and microscopic evaluation of the viability of seeded cells was tested
      with a PKH 67 fluorescent dye. To assess the cellular toxicity the proliferation
      of fibroblasts adjacent to the tested polymers was examined. The vitability of
      cells seeded on polymers was also evaluated by measuring the fluorescence
      intensity of calcein which binds only to live cells. The conducted experiments
      (DAPI and PKH 67 staining) show that the tested materials have a positive
      influence on cell adhesion crucial for wound healing - fibroblasts. The self-made
      dibutyrylchitin dressing do not cause the reduction of viability of cells seeded
      on them. The in vitro study illustrated the interactions between the tested
      materials, constructed of calcium alginate or dibutyrylchitin and mouse
      fibroblasts and proved their usefulness in the design of cellular scaffolds.
      Examined polymers turned out to be of great interest and promise for cellular
      scaffolds design. 

PMID- 25748621
TI  - Genes and childhood leukemia.
AB  - Leukemia is a heterogeneous hematologic malignancy originating from a multipotent
      hematopoietic stem cell. It ranks among the commonest cancers in childhood and is
      characterized by excessive proliferation and differentiation block. The process
      of leukemogenesis is governed by genetic changes at both the cytogenetic and
      molecular level. According to numerous analyses, a large spectrum of mutations
      and rearrangements underlying the disease affect essential cellular transduction
      pathways, genes ensuring proper course of hematopoiesis, oncogenes, tumor
      suppressors and apoptosis regulators. Common lesions include translocations to T
      cell receptor (TCR) loci in T-lineage acute lymphoblastic leukemia (T-ALL),
      mutations of transcription factors regulating B-lineage development and cell
      maturation in B-lineage acute lymphoblastic leukemia (B-ALL) (PAX5, TCF3, EBF1,
      etc.), aberrational disruption of genes coding for transcription factors and
      coactivators in acute myeloid leukemia (AML) (e.g. CBF) or BCR-ABL1 fusion and
      activation of multiple kinases in chronic myeloid leukemia (CML). These
      alterations severely impair cell function. Broadening knowledge of the genetic
      background gives an insight into the pathobiology of a disease and allows for a
      better understanding of it. An appropriate investigation of genomic events yields
      diagnostic, prognostic and therapeutic implications. Broadening knowledge of the
      pathogenesis of leukemia seems to be a promising contribution to precise
      stratification of patients, reducing the toxicity and adverse effects caused by
      medical intervention, treatment personalization and introduction of targeted
      therapy accessible to a wide range of patients. 

PMID- 25748622
TI  - [Amylin under examination. Fibrillation - cytotoxic pancreatic polypeptide
      aggregation].
AB  - In patients or animals affected by type 2 diabetes mellitus (DM2, non-insulin
      dependent diabetes mellitus [NIDDM]), some pathological deposits, called amyloid,
      are observed among cells of islets of Langerhans. Among other constituents, the
      deposits consist of an insoluble, fibrillar form of polypeptide neurohormone
      called amylin, produced by pancreatic beta cells. It is thought that formation of
      fibrillar deposits of misfolded and aggregated polypeptide is highly toxic to
      beta cells and leads to cell dysfunction, cell loss, pancreas destruction and
      progress of the disease. Due to the extreme insolubility of this polypeptide and
      its instant fibrillation, amylin constitutes a methodological problem, and there
      is a need for a special methodology in experiments. Some mechanisms and factors
      that govern amylin fibrillization are rather poorly understood. This article
      presents amylin as a fibrillating molecule and some methods and methodological
      aspects and problems that emerge at successive steps during the fibrillation
      process, including hypothesized cytotoxicity mechanisms of this polypeptide. 

PMID- 25748623
TI  - Seroprevalence of anti-HEV IgG in 182 Polish patients.
AB  - INTRODUCTION: Hepatitis E virus (HEV) infection is an emergent disease in
      developed countries. HEV seroprevalence in such areas significantly exceeds
      values expected when one considers infection with this virus only as a problem
      restricted to classical endemic regions. To date, no related data are available
      in Poland. In this study we aimed to obtain HEV seroprevalence data and compare
      them with similar data for hepatitis A virus (HAV) in Polish patients.
      MATERIAL/METHODS: From February 1st, 2013, to October 15th, 2013, we performed
      anti-HEV IgG (anti-HEV) tests (EIAgen HEV IgG Kit; Adaltis, Milano, Italy) in 182
      patients (101 men and 81 women; 61 patients were HIV-positive) of one center in
      Poland, aged 19-85 (47.2 +/- 14.2 years). RESULTS: We found a 15.9%
      seropositivity rate for anti-HEV (16.3% of the study population with an
      unequivocal test result) and 38.5% for anti-HAV. In 6 cases (3.4%), anti-HEV
      positive persons had never travelled abroad. In contrast to HAV seroprevalence
      data, there was no significant difference in HEV seroprevalence between young
      adults (18-40 years) and older patients (p<0.0001 and p=0.0967, respectively).
      Anti-HEV were found in 21.3% of HIV-infected individuals. CONCLUSIONS: HEV
      infection may occur in Poland. Anti-HAV seropositivity among Polish patients is
      significantly higher than anti-HEV. In contrast to HAV, HEV seroprevalence is
      similar in younger and older patients. The clinical course of HEV infection in
      Polish citizens seems to be largely asymptomatic. Polish HIV patients may be more
      commonly exposed to HEV than similar individuals from other countries.

PMID- 25748624
TI  - [Perinatal sources of stem cells].
AB  - Recently, stem cell biology has become an interesting topic. Several varieties of
      human stem cells have been isolated and identified in vivo and in vitro.
      Successful application of hematopoietic stem cells in hematology has led to the
      search for other sources of stem cells and expanding the scale of their
      application. Perinatal stem cells are a versatile cell population, and they are
      interesting for both scientific and practical objectives. Stem cells from
      perinatal tissue may be particularly useful in the clinic for autologous
      transplantation for fetuses and newborns, and after banking in later stages of
      life, as well as for in utero transplantation in the case of genetic disorders.
      In this review paper we focus on the extraction and therapeutic potential of stem
      cells derived from perinatal tissues such as the placenta, the amnion, amniotic
      fluid, umbilical cord blood and Wharton's jelly. 

PMID- 25748625
TI  - GM-CSF as a target in inflammatory/autoimmune disease: current evidence and
      future therapeutic potential.
AB  - Granulocyte-macrophage colony-stimulating factor (GM-CSF) can be viewed as a pro
      inflammatory cytokine rather than as a key regulator of steady state and systemic
      myelopoiesis. Key aspects of GM-CSF biology need to be clarified such as pro
      survival vs activation/differentiation function, its cellular sources, its
      responsive cell populations, its downstream mediators/pathways, and when GM-CSF
      is relevant. Striking effects of GM-CSF depletion/deletion in some pre-clinical
      autoimmune/inflammation models have been reported. Systemic effects of
      administered GM-CSF are not necessarily informative about its local blockade in
      disease. Recent clinical RA trials, particularly Phase II trials with
      mavrilimumab (anti-GM-CSFRalpha Ab), show rapid and impressive efficacy with no
      significant adverse effects. Larger and longer trials targeting GM-CSF are needed
      and with careful monitoring of unwanted side effects. This review summarizes the
      most recent information on these topics. 

PMID- 25748627
TI  - 2014: Passing of the guard in International Child Neurology.

PMID- 25748626
TI  - HDAC4-myogenin axis as an important marker of HD-related skeletal muscle atrophy.
AB  - Skeletal muscle remodelling and contractile dysfunction occur through both acute
      and chronic disease processes. These include the accumulation of insoluble
      aggregates of misfolded amyloid proteins that is a pathological feature of
      Huntington's disease (HD). While HD has been described primarily as a
      neurological disease, HD patients' exhibit pronounced skeletal muscle atrophy.
      Given that huntingtin is a ubiquitously expressed protein, skeletal muscle fibres
      may be at risk of a cell autonomous HD-related dysfunction. However the mechanism
      leading to skeletal muscle abnormalities in the clinical and pre-clinical HD
      settings remains unknown. To unravel this mechanism, we employed the R6/2
      transgenic and HdhQ150 knock-in mouse models of HD. We found that symptomatic
      animals developed a progressive impairment of the contractile characteristics of
      the hind limb muscles tibialis anterior (TA) and extensor digitorum longus (EDL),
      accompanied by a significant loss of motor units in the EDL. In symptomatic
      animals, these pronounced functional changes were accompanied by an aberrant
      deregulation of contractile protein transcripts and their up-stream
      transcriptional regulators. In addition, HD mouse models develop a significant
      reduction in muscle force, possibly as a result of a deterioration in energy
      metabolism and decreased oxidation that is accompanied by the re-expression of
      the HDAC4-DACH2-myogenin axis. These results show that muscle dysfunction is a
      key pathological feature of HD. 

PMID- 25748628
TI  - Clinical features and long-term outcome of a group of Japanese children with
      inflammatory central nervous system disorders and seropositivity to myelin
      oligodendrocyte glycoprotein antibodies.
AB  - BACKGROUND: Myelin-oligodendrocyte glycoprotein and aquaporin-4 have been
      extensively analyzed as targets for humoral immune reactions in central nervous
      system (CNS) demyelinating diseases, and the results indicated a possible role of
      these antibodies in the pathogenesis of various demyelinating diseases.
      OBJECTIVE: To investigate the antibody titer levels against myelin
      oligodendrocyte glycoprotein and aquaporin-4 in pediatric patients with
      inflammatory CNS disorders, and to evaluate clinical significance to study anti
      myelin-oligodendrocyte glycoprotein antibodies. METHODS: Sera at onset from
      patients with acute disseminated encephalomyelitis (ADEM) in 7, optic neuritis
      (ON) in 5, pediatric MS in 4 and neuromyelitis optica in one were tested for
      myelin-oligodendrocyte glycoprotein and aquaporin-4 antibodies using cell-based
      assays with live transfected cells. The duration of the observation periods
      ranged from 1 to 21 years (median, 10 years). We also described clinical course
      of patients with positive anti-myelin-oligodendrocyte glycoprotein antibodies.
      RESULTS: Among 17 patients diagnosed with inflammatory CNS demyelinating diseases
      nine (52%) were positive to anti-myelin-oligodendrocyte glycoprotein antibodies.
      Of note, all cases with positive anti-myelin-oligodendrocyte glycoprotein
      antibodies showed seronegativity against anti-aquaporin-4 antibodies and had a
      favorable prognosis. CONCLUSIONS: This preliminary report showed that anti-myelin
      oligodendrocyte glycoprotein antibodies testing at onset could be a useful tool
      predicting clinical outcome of children with ADEM, ON, and MS.

PMID- 25748629
TI  - Cortisol is not associated with telomere shortening or chromosomal instability in
      human lymphocytes cultured under low and high folate conditions.
AB  - Chronic psychological stress and nutritional deficiencies are factors that impact
      negatively on human health and disease risk. Chronic stress has been associated
      with accelerated leukocyte telomere shortening in numerous cohorts, however, a
      mechanistic link has proven elusive. This study tested the hypotheses that
      chronic exposure to the stress hormone, cortisol, causes telomere shortening and
      chromosome instability (CIN) in vitro, and that these effects would be further
      exacerbated by folate (vitamin B9) deficiency. Primary human lymphocytes were
      maintained in vitro for 12 days in medium containing either 25 nM folic acid
      (FA(low)) or 100 nM FA (FA(high)), together with either 0, 400, 1000 or 3500 nM
      cortisol. The interactive effects of cortisol and FA were examined by comparing
      telomere length (TL), biomarkers of DNA damage, and cytostasis. At day 12 TL was
      5-17% longer in lymphocytes cultured in FA(low) conditions (mean +/- SD;10.2% +/-
      1.6), compared with those in FA(high) medium (9.1% +/- 1, p = 0.02). Refuting the
      hypothesis, TL was consistently greater in the presence of cortisol. The effect
      of FA deficiency on the frequency of DNA damage was significant for nucleoplasmic
      bridges, circular nuclei, micronuclei and nuclear buds, (p < 0.0001-0.001). The
      effect of cortisol, however, was negligible, only reaching statistical
      significance for the frequency of fused nuclei (p = 0.04). Cortisol was
      significantly associated with reduced cell division and growth and had an
      apparent protective effect on cell viability in the FA(low) conditions.
      Conclusions: Both chronic cortisol exposure, and folate deficiency, resulted in
      telomere elongation, however, the effect of cortisol was marginal relative to
      that of folate. Cortisol was not associated with increased chromosomal
      instability, but caused a significant reduction in cell division and growth.
      Together these results indicate that cortisol is not directly genotoxic and that
      the telomere shortening associated with increased psychological stress in vivo
      may not be explained by a direct effect of cortisol.

PMID- 25748630
TI  - Lower radiation burden in state of the art fluoroscopic cystography compared to
      direct isotope cystography in children.
AB  - INTRODUCTION: Both, fluoroscopic voiding cystourethrography (fVCUG) and direct
      isotope cystography (DIC) are diagnostic tools commonly used in pediatric
      urology. Both methods can detect vesicoureteral reflux (VUR) with a high
      sensitivity. Whilst the possibility to depict anatomical details and important
      structures as for instance the urethra in boys or the detailed calyceal anatomy
      are advantages of fVCUG, a lower radiation burden is thought to be the main
      advantage of DIC. In the last decade, however, a rapid technical evolution has
      occurred in fluoroscopy by implementing digital grid-controlled, variable rate,
      pulsed acquisition technique. As documented in literature this led to a
      substantial decrease in radiation burden conferred during fVCUGs. OBJECTIVE: To
      question the common belief that direct isotope cystography confers less radiation
      burden compared to state of the art fluoroscopic voiding cystography. STUDY
      DESIGN: Radiation burden of direct isotope cystography in 92 children and in
      additional 7 children after an adaption of protocol was compared to radiation
      burden of fluoroscopic voiding cystourethrography in 51. The examinations were
      performed according to institutional protocols. For calculation of mean effective
      radiation dose [mSv] for either method published physical models correcting for
      age and sex were used. For DIC the model published by Stabin et al., 1998 was
      applied, for fVCUG two different physical models were used (Schultz et al., 1999,
      Lee et al., 2009). RESULTS: The radiation burden conferred by direct isotope
      cystography was significantly higher as for fluoroscopic voiding
      cystourethrography. The mean effective radiation dose for direct isotope
      cystography accounted to 0.23 mSv (+/- 0.34 m, median 0.085 mSv) compared to
      0.015 mSv (+/- 0.013, median 0.008 mSv, model by Schultz et al.) - 0.024 mSv (+/-
      0.018, median 0.018 mSv, model by Lee et al.) for fluoroscopic voiding
      cystourethrography. After a protocol adaption to correct for a longer examination
      time in DIC that was caused by filling until calculated bladder capacity, mean
      radiation burden accounted to .07 mSv (median 0.07 mSv) and the values were less
      scattered. DISCUSSION: As it had to be expected from literature, radiation dose
      from fVCUG, if modern image acquisition techniques are used, is even less than
      from DIC. In our protocol, according to nuclear medicine standards, bladders were
      filled until calculated capacity. This resulted in a longer examination time for
      the patients with a higher functional capacity, resulting in relatively higher
      radiation burden. However, also if the protocol is changed or only the patients
      with relatively fast bladder emptying are considered, radiation burden conferred
      by DIC is higher (at least * 2.9, comparing the "worst" case for fVCUG with the
      "best" case for DIC). Absolute radiation burden conferred by either exam is
      extremely low compared to other medical radiation exposures as well as to
      environmental radiation. Consequently it is most probably not relevant for the
      individual childs future risk for cancer or other radiation damage. However,
      because of repeated investigations with correspondingly higher radiation burden
      in this patient group the ALARA (as low as reasonably achievable) principle
      should lead to a optimized use of fVCUG rather than an uncritical use of DIC,
      given that modern acquisition standards are available and radiation measurement
      is performed. Also, fVCUG provides more information concerning anatomical details
      compared to DIC. CONCLUSION: Contrary to common beliefs, effective radiation dose
      conferred during fluoroscopic voiding cystourethrography is significantly lower
      than during direct isotope cystography. The prerequisite for our findings,
      however, is the use of modern image acquisition tools and an optimized protocol.
      Both exams confer low radiation doses probably only relevant to children
      undergoing repeated radiation exposure. Nevertheless, this findings should be
      considered in indication for either exam in order to reduce the radiation burden
      to a minimum whilst optimizing the information yield.

PMID- 25748631
TI  - Can endoscopic balloon dilation for primary obstructive megaureter be effective
      in a long-term follow-up?
AB  - BACKGROUND: Ureteral tapering and reimplantation is an established treatment for
      persistent or progressive primary obstructive megaureter (POM) but may result in
      complications and morbidity. Use of a less invasive technique involving
      endoscopic balloon dilation appears very interesting. OBJECTIVE: The objective of
      this report is to determine if endoscopic balloon dilation for POM is effective
      in the long term as well as to assess complications of the procedure. MATERIAL
      AND METHODS: A retrospective review was done on 19 patients and 20 ureters
      treated with the endoscopic balloon dilation by POM from June 2000 to February
      2010. Surgery was performed solely in those cases in which there was persistence
      of obstruction in the renogram along with one or all of the following conditions:
      impairment of the differential renal function <40%, worsening of the renal pelvic
      dilation, febrile UTI in spite of antibiotic prophylaxis or renal calculi. The
      patients comprised 16 boys and 3 girls with a mean age at surgery of 17 months
      (range 1-44 months). Ten cases were left sided, eight right sided, and one
      bilateral. Under endoscopic and fluoroscopic guidance, a 3-5 Fr dilating balloon
      was inflated to 12-14 atm, or until disappearance of the stenotic obstructive
      area. A double J stent was positioned and withdrawn 2 months later. Follow-up
      recorded the presence of symptoms, number of reintervention procedures
      registered, and included renal ultrasound and MAG-3 renogram. RESULTS: There were
      no perioperative complications. Eighteen ureters showed a non-obstructive pattern
      on MAG-3 renogram after the first endoscopic dilation, representing a 90% success
      rate. One case required a second dilation, which proved successful and two cases
      of recurrent lithiasis required ureterotomy without instances of obstruction. 2
      patients had a febrile UTI and a vesicoureteral reflux was diagnosed in one.
      Renal function was preserved in 95% of patients. The mean follow-up was 6.9 years
      (range 3.9-13.3 years). One patient was lost after the procedure. DISCUSSION: In
      an era of minimally invasive techniques, the search for less invasive procedures
      for treatment of POM has resulted in a variety of surgical options. Angulo et
      al., in 1998 and our group described the first POM treatment with endoscopic
      balloon dilation, which is believed to be a definitive, less invasive, and safe
      treatment. Furthermore, should an endoscopic approach fail, reimplant surgery can
      be performed. Few publications have reported short series with good results in
      the short and medium term. Torino et al. presented five cases in children aged
      less than 1 year, none of these showed evidence of obstruction. Garcia-Aparicio
      et al. presented a series of 13 patients treated with a success rate of 84.6%.
      Christman et al. added laser incision in cases of narrowed ureteral segment 2-3
      cm long and used double stenting. Good outcomes were presented in 71%. Romero et
      al. reported improvement of drainage within the first 18 months after treatment
      in 69% of patients. The potential de novo onset of vesicoureteral reflux may be
      the source of some controversy. We consider that dilation does not significantly
      alter the antireflux mechanism. In VCUG is not systematically performed because
      it is an invasive test. This restricts the conclusions that can be drawn from our
      findings. Nevertheless, some groups continue to systematically perform VCUG.
      CONCLUSIONS: Endoscopic balloon dilation for POM is a safe, feasible, and less
      invasive procedure that shows good outcomes on long-term follow-up. However,
      multicenter studies and prospective trials should be encouraged to provide more
      definitive evidence on its benefits.

PMID- 25748632
TI  - Is There Consistency between the Binding Affinity and Inhibitory Potential of
      Natural Polyphenols as alpha-amylase Inhibitors?
AB  - The inhibitory potential of natural polyphenols for alpha-amylases has attracted
      great interests among researchers. The structure-affinity properties of natural
      polyphenols binding to alpha-amylase and the structure-activity relationship of
      dietary polyphenols inhibiting alpha-amylase were deeply investigated. There is a
      lack of consistency between the structure-affinity relationship and the structure
      activity relationship of natural polyphenols as alpha-amylase inhibitors. Is it
      consistent between the binding affinity and inhibitory potential of natural
      polyphenols as with alpha-amylase inhibitors? It was found that the consistency
      between the binding affinity and inhibitory potential of natural polyphenols as
      with alpha-amylase inhibitors is not equivocal. For example, there is no
      consistency between the binding affinity and the inhibitory potential of
      quercetin and its glycosides as alpha-amylase inhibitors. However, catechins with
      higher alpha-amylase inhibitory potential exhibited higher affinity with alpha
      amylase. 

PMID- 25748633
TI  - Using poetry and art analysis to evoke critical thinking and challenging
      reflection in senior-level nutrition students.

PMID- 25748635
TI  - Asymmetrical squaraines for high-performance small-molecule organic solar cells
      with a short circuit current of over 12 mA cm(-2).
AB  - An asymmetrical squaraine dye (Py-3) with its two electron-donating aryl groups
      directly linked to the electron-withdrawing squaric acid core possesses an ideal
      bandgap of 1.33 eV, together with an intense and broad absorption band in the
      range 550-950 nm. Hence, the resulting solution-processed solar cells display an
      impressive Jsc of 12.03 mA cm(-2) and a PCE of 4.35%.

PMID- 25748634
TI  - Household factors, family behavior patterns, and adherence to dietary and
      physical activity guidelines among children at risk for obesity.
AB  - OBJECTIVE: To describe the proportion of children adhering to recommended
      physical activity and dietary guidelines, and examine demographic and household
      correlates of guideline adherence. DESIGN: Cross-sectional (pre-randomization)
      data from a behavioral intervention trial designed to prevent unhealthy weight
      gain in children. PARTICIPANTS: A total of 421 children (aged 5-10 years) at risk
      for obesity (body mass index percentile, 70-95). MAIN OUTCOMES MEASURED: Physical
      activity (accelerometry), screen time (parent survey), and fruit and vegetable
      and sugar-sweetened beverage intake (24-hour dietary recall). ANALYSIS:
      Proportions meeting guidelines were calculated. Logistic regression examined
      associations between demographic and household factors and whether children met
      recommended guidelines for (1) physical activity (>= 60 min/d), (2) screen time
      (<= 2 h/d), (3) fruit and vegetable intake (>= 5 servings/d), and (4) sugar
      sweetened beverage avoidance. RESULTS: Few children met more than 1 guideline.
      Only 2% met all 4 recommended guidelines and 19% met none. Each guideline had
      unique sociodemographic and domain-specific household predictors (ie,
      availability of certain foods and beverages, media, and active play and exercise
      equipment). CONCLUSIONS AND IMPLICATIONS: Families equipped to promote healthy
      child behavior patterns in 1 activity or dietary domain may not be in others.
      Results have implications for the development of interventions to affect
      children's weight-related behaviors and growth trajectories.

PMID- 25748636
TI  - Measurement of off-diagonal transport coefficients in two-phase flow in porous
      media.
AB  - The prevalent description of low capillary number two-phase flow in porous media
      relies on the independence of phase transport. An extended Darcy's law with a
      saturation dependent effective permeability is used for each phase. The driving
      force for each phase is given by its pressure gradient and the body force. This
      diagonally dominant form neglects momentum transfer from one phase to the other.
      Numerical and analytical modeling in regular geometries have however shown that
      while this approximation is simple and acceptable in some cases, many practical
      problems require inclusion of momentum transfer across the interface. Its
      inclusion leads to a generalized form of extended Darcy's law in which both the
      diagonal relative permeabilities and the off-diagonal terms depend not only on
      saturation but also on the viscosity ratio. Analogous to application of
      thermodynamics to dynamical systems, any of the extended forms of Darcy's law
      assumes quasi-static interfaces of fluids for describing displacement problems.
      Despite the importance of the permeability coefficients in oil recovery, soil
      moisture transport, contaminant removal, etc., direct measurements to infer the
      magnitude of the off-diagonal coefficients have been lacking. The published data
      based on cocurrent and countercurrent displacement experiments are necessarily
      indirect. In this paper, we propose a null experiment to measure the off-diagonal
      term directly. For a given non-wetting phase pressure-gradient, the null method
      is based on measuring a counter pressure drop in the wetting phase required to
      maintain a zero flux. The ratio of the off-diagonal coefficient to the wetting
      phase diagonal coefficient (relative permeability) may then be determined. The
      apparatus is described in detail, along with the results obtained. We demonstrate
      the validity of the experimental results and conclude the paper by comparing
      experimental data to numerical simulation. 

PMID- 25748637
TI  - Cellular and biological evaluation and diagnostic immunohistochemistry of
      cytokeratin 15/19 expression in distinguishing cutaneous basal cell carcinoma.
AB  - Recent studies have investigated the expression of proliferative markers, but
      little is known about the expression of cytokeratin 15 and 19 in different
      histological subtypes of basal cell carcinoma (BCC). We conducted cellular,
      biological, clinicopathological and immunohistochemical analysis on the
      manifestations of 8 BCC by hematoxylin and eosin stain (H&E) staining and
      immunohistochemistry and reviewed relevant literature. Microscopically, the tumor
      cells were multiple remarkable foci of epidermolytic hyperkeratosis with large
      pleomorphic nuclei and scant cytoplasm together with peripheral palisading and
      forming solid nests. Furthermore, the most tumors were composed of highly
      cellular areas with a homogenous population of round, ovoid and spindle cells,
      hyperchromatic nuclei, high cellular pleomorphism, high mitotic index and various
      morphologic patterns. Moreover, the tumors displayed an invasive growth, with
      positive expression of Cytokeratin 19 (CK19) and negative expression of CK15. Our
      study revealed that the expression of CK19 was associated with progression and
      invasion in cases with BCC and immunohistochemistry is indispensable in
      distinguishing this tumor from other types of cutaneous carcinoma. To our best
      knowledge, it may be a considerable biomarker to assess invasiveness of cutaneous
      surface BCC and to guide clinical management of such tumors. 

PMID- 25748638
TI  - Detection of replication competent adenovirus upon serial passaging of
      recombinant adenovirus expressing FMDV capsid proteins.
AB  - Replication deficient human adenovirus type 5 (hAd5) is an important gene
      delivery vehicle and has been used in various fields of biomedical sciences such
      as gene therapy, cancer therapy and vaccination. Inspite of its various useful
      features, emergence of replication competent adenovirus (RCA) in recombinant
      virus stocks is a great concern. In the present study, recombinant adenovirus
      expressing foot-and-mouth disease virus serotype-O capsid proteins was propagated
      in HEK-293 cells and purified by CsCl density gradient ultracentrifugation. The
      virus was serially passaged in HEK-293 cells and at passage level (P) 2-4, 6, 8
      and 12, tested for the presence of RCA. A vector dose of 2 * 10(8) and 1 * 10(10)
      TCID50 of the virus was used in cell line bioassay and PCR, respectively. Our
      results demonstrated that the PCR is more sensitive and rapid technique for the
      detection of RCA in recombinant adenovirus stocks as early as at P3, whereas the
      bioassay detected the RCA at P8.

PMID- 25748639
TI  - Reductive benzylation of singly bonded 1,2,4,15-C60 dimers with an oxazoline or
      imidazoline heterocycle: unexpected formation of 1,2,3,16-C60 adducts and
      insights into the reactivity of singly bonded C60 dimers.
AB  - Upon reduction, singly bonded 1,2,4,15-C60 dimers with an oxazoline or
      imidazoline heterocycle dissociate into monoanionic 1,2,4-C60 intermediates,
      which surprisingly leads to the formation of 1,2,3,16-C60 rather than 1,2,4,15
      C60 adducts of the original configuration by further benzylation, even though the
      analogue of dibenzylated C60 oxazoline with a 1,2,4,15-configuration is stable
      and has been obtained. These results are corroborated by computational
      calculations, which rationalize the reaction and clarify the structure of the
      1,2,3,16-C60 adducts, providing new insights into the intrinsic reactivity of
      singly bonded C60 dimers. 

PMID- 25748640
TI  - Controllable thermal rectification realized in binary phase change composites.
AB  - Phase transition is a natural phenomenon happened around our daily life,
      represented by the process from ice to water. While melting and solidifying at a
      certain temperature, a high heat of fusion is accompanied, classified as the
      latent heat. Phase change material (PCM) has been widely applied to store and
      release large amount of energy attributed to the distinctive thermal behavior.
      Here, with the help of nanoporous materials, we introduce a general strategy to
      achieve the binary eicosane/PEG4000 stuffed reduced graphene oxide aerogels,
      which has two ends with different melting points. It's successfully demonstrated
      this binary PCM composites exhibits thermal rectification characteristic. Partial
      phase transitions within porous networks instantaneously result in one end of the
      thermal conductivity saltation at a critical temperature, and therefore switch on
      or off the thermal rectification with the coefficient up to 1.23. This value can
      be further raised by adjusting the loading content of PCM. The uniqueness of this
      device lies in its performance as a normal thermal conductor at low temperature,
      only exhibiting rectification phenomenon when temperature is higher than a
      critical value. The stated technology has broad applications for thermal energy
      control in macroscopic scale such as energy-efficiency building or nanodevice
      thermal management. 

PMID- 25748641
TI  - Feasibility of a Mobile Phone-Based Surveillance for Surgical Site Infections in
      Rural India.
AB  - OBJECTIVES: To assess the feasibility of using mobile communication technology in
      completing a 30-day follow-up of surgical site infection (SSI). SUBJECTS AND
      METHODS: SSIs are infections occurring up to 30 days after an operative
      procedure. This prospective exploratory study was conducted in a cohort of
      patients who were admitted and operated on in the general surgery wards of a
      rural hospital in India from October 2010 to June 2011. At the time of discharge,
      all patients were requested to follow-up in the surgical outpatient clinic at 30
      days after surgery. If this was not done, a mobile phone-based surveillance was
      done to complete the follow-up. RESULTS: The mean age of the 536 operated-on
      patients was 40 years (95% confidence interval [CI], 38-41 years). The mean
      duration of hospital stay was 10.7 days (95% CI, 9.9-11.6 days). Most (81%)
      operated-on patients were from rural areas, and 397 (75%) were male. Among the
      operated-on patients the ownership of mobile phones was 75% (95% CI, 73-78%). The
      remaining 25% of patients (n=133) used a shared mobile phone. For 380 patients
      (74.5%) the follow-up was completed by mobile phones. The SSI rate at follow-up
      was 6.3% (n=34). In 10 patients, an SSI was detected over the mobile phone.
      CONCLUSIONS: Mobile communication technology is feasible to be used in rural
      settings to complete case follow-up for SSIs.

PMID- 25748642
TI  - Short-term effect of topical brinzolamide 1%-timolol 0.5% fixed combination on
      human central corneal thickness.
AB  - PURPOSE: To evaluate the short-term effect of fixed combination of brinzolamide
      1% and timolol 0.5% (FCBT) application on human central corneal thickness (CCT).
      METHODS: This prospective clinical study included 97 patients having Nd:YAG laser
      posterior capsulotomy for posterior capsule opacification. Patients were
      randomized to receive apraclonidine hydrochloride 0.5% (APRA) (n=48) or FCBT
      (n=49) at 1 h before laser surgery. The baseline CCT was evaluated by
      ultrasonographic pachymetry from the central region ~1 h before the laser
      procedure. CCT measurements were applied just before the laser application and
      then the first, second, and third hour, and the first, third, and seventh day
      after the Nd:YAG laser capsulotomy. RESULTS: There was no statistically
      significant difference between the baseline intraocular pressures, CCTs, and
      demographic and clinical data (age, sex, surgery laser interval, total laser
      energy) of the APRA and the FCBT groups. The mean CCT values of the APRA group at
      the first, second, and third hour, and the first, third, and seventh day were
      553.8+/-28.0, 551.4+/-35.3, 556.8+/-28.7, 552.6+/-27.5, 548.2+/-26.2, and 546.2+/
      25.5 MUm, respectively. The mean CCT values of the FCBT group at the first,
      second, and third hour, and the first, third, and seventh day were 544.21+/-34.4,
      549.4+/-27.6, 555.94+/-33.1, 550.8+/-33.4, 547.2+/-33.6, and 544.9+/-33.4 MUm,
      respectively. No statistically significant difference was detected between the 2
      groups. CONCLUSION: The difference in CCT increase between both groups was not
      statistically significant at any follow-up visits. FCBT application does not have
      a short-term effect on CCT.

PMID- 25748643
TI  - Evidence of the generation of isosaccharinic acids and their subsequent
      degradation by local microbial consortia within hyper-alkaline contaminated
      soils, with relevance to intermediate level radioactive waste disposal.
AB  - The contamination of surface environments with hydroxide rich wastes leads to the
      formation of high pH (>11.0) soil profiles. One such site is a legacy lime works
      at Harpur Hill, Derbyshire where soil profile indicated in-situ pH values up to
      pH 12. Soil and porewater profiles around the site indicated clear evidence of
      the presence of the alpha and beta stereoisomers of isosaccharinic acid (ISA)
      resulting from the anoxic, alkaline degradation of cellulosic material. ISAs are
      of particular interest with regards to the disposal of cellulosic materials
      contained within the intermediate level waste (ILW) inventory of the United
      Kingdom, where they may influence radionuclide mobility via complexation events
      occurring within a geological disposal facility (GDF) concept. The mixing of
      uncontaminated soils with the alkaline leachate of the site resulted in ISA
      generation, where the rate of generation in-situ is likely to be dependent upon
      the prevailing temperature of the soil. Microbial consortia present in the
      uncontaminated soil were capable of surviving conditions imposed by the alkaline
      leachate and demonstrated the ability to utilise ISAs as a carbon source.
      Leachate-contaminated soil was sub-cultured in a cellulose degradation product
      driven microcosm operating at pH 11, the consortia present were capable of the
      degradation of ISAs and the generation of methane from the resultant H2/CO2
      produced from fermentation processes. Following microbial community analysis,
      fermentation processes appear to be predominated by Clostridia from the genus
      Alkaliphilus sp, with methanogenesis being attributed to Methanobacterium and
      Methanomassiliicoccus sp. The study is the first to identify the generation of
      ISA within an anthropogenic environment and advocates the notion that microbial
      activity within an ILW-GDF is likely to influence the impact of ISAs upon
      radionuclide migration. 

PMID- 25748644
TI  - New rubrolide analogues as inhibitors of photosynthesis light reactions.
AB  - Natural products called rubrolides have been investigated as a model for the
      development of new herbicides that act on the photosynthesis apparatus. This
      study comprises a comprehensive analysis of the photosynthesis inhibitory ability
      of 27 new structurally diverse rubrolide analogues. In general, the results
      revealed that the compounds exhibited efficient inhibition of the photosynthetic
      process, but in some cases low water solubility may be a limiting factor. To
      elucidate their mode of action, the effects of the compounds on PSII and PSI, as
      well as their partial reaction on chloroplasts and the chlorophyll a fluorescence
      transients were measured. Our results showed that some of the most active
      rubrolide analogues act as a Hill reaction inhibitors at the QB level by
      interacting with the D1 protein at the reducing side of PSII. All of the active
      analogues follow Tice's rule of 5, which indicates that these compounds present
      physicochemical properties suitable for herbicides. 

PMID- 25748645
TI  - Discovering what is hidden: The role of non-ritualized covert neutralizing
      strategies in Obsessive-Compulsive Disorder.
AB  - BACKGROUND AND OBJECTIVES: Neutralizing strategies are secondary to obsessions
      and an additional cause of distress and interference, but they have received
      little attention in theories and research, especially the non-ritualized covert
      strategies. This study focuses on the comparative impact of non-ritualized covert
      and compulsive-overt strategies in the course of OCD. METHODS: Eighty-two OCD
      adult patients completed measures assessing distress, interference, appraisals
      and overt and covert neutralizing strategies to control obsessions. Thirty-eight
      patients who had completed cognitive therapy were assessed again after treatment.
      RESULTS: Only overt compulsions are associated with OCD severity. Nonetheless,
      considering the main symptom dimension, covert strategies are also associated
      with severity in patients with moral-based obsessions. Patients who used covert
      strategies more frequently, compared to those who use them less, reported more
      sadness, guilt, control importance, interference, and dysfunctional appraisals.
      Regarding the overt strategies, patients who used them more reported more anxiety
      and ascribed more personal meaning to their obsessions than the patients who used
      them less. After treatment, recovered patients decreased their use of both covert
      and overt strategies, while non-recovered patients did not. There was a higher
      rate of non-recovered patients among those who used more non-ritualized covert
      strategies before treatment. LIMITATIONS: Emotions and appraisals were assessed
      with a single item. OCD symptom dimensions were only assessed by the Obsessive
      Compulsive Inventory. CONCLUSIONS: In addition to studying overt compulsions, the
      impact of covert neutralizing strategies on the OCD course and severity warrants
      more in-depth study.

PMID- 25748646
TI  - Seeing is saving: the benefit of 3D imaging in gynecologic brachytherapy.
AB  - Despite a concerning decline in the use of brachytherapy over the past decade, no
      other therapy is able to deliver a very high dose of radiation into or near a
      tumor, with a rapid fall-off of dose to adjacent structures. Compared to
      traditional X-ray-based brachytherapy that relies on points, the use of CT and MR
      for 3D planning of gynecologic brachytherapy provides a much more accurate volume
      based calculation of dose to an image-defined tumor and to the bladder, rectum,
      sigmoid, and other pelvic organs at risk (OAR) for radiation complications. The
      publication of standardized guidelines and an online contouring teaching atlas
      for performing 3D image-based brachytherapy has created a universal platform for
      communication and training. This has resulted in a uniform approach to using
      image-guided brachytherapy for treatment and an internationally accepted format
      for reporting clinical outcomes. Significant improvements in survival and
      reductions in toxicity have been reported with the addition of image guidance to
      increase dose to tumor and decrease dose to the critical OAR. Future improvements
      in individualizing patient treatments should include a more precise definition of
      the target. This will allow dose modulation based on the amount of residual
      disease visualized on images obtained at the time of brachytherapy.

PMID- 25748647
TI  - Serrated lesions in colorectal cancer screening: detection, resection, pathology
      and surveillance.

PMID- 25748648
TI  - Global patterns of cardia and non-cardia gastric cancer incidence in 2012.
AB  - OBJECTIVE: Globally, gastric cancer incidence shows remarkable international
      variation and demonstrates distinct characteristics by the two major
      topographical subsites, cardia (CGC) and non-cardia (NCGC). Because global
      incidence estimates by subsite are lacking, we aimed to describe the worldwide
      incidence patterns of CGC and NCGC separately. DESIGN: Using Cancer Incidence in
      Five Continents Volume X (CI5X), we ascertained the proportions of CGC and NCGC
      by country, sex and age group (<65 and >=65 years). These derived proportions
      were applied to GLOBOCAN 2012 data to estimate country-specific age-standardised
      CGC and NCGC incidence rates (ASR). Regional proportions were used to estimate
      rates for countries not included in CI5X. RESULTS: According to our estimates, in
      2012, there were 260,000 cases of CGC (ASR 3.3 per 100,000) and 691,000 cases of
      NCGC (ASR 8.8) worldwide. The highest regional rates of both gastric cancer
      subsites were in Eastern/Southeastern Asia (in men, ASRs: 8.7 and 21.7 for CGC
      and NCGC, respectively). In most countries NCGC occurred more frequently than CGC
      with an average ratio of 2:1; however, in some populations where NCGC incidence
      rates were lower than the global average, CGC rates were similar or higher than
      NCGC rates. Men had higher rates than women for both subsites but particularly
      for CGC (male-to-female ratio 3:1). CONCLUSIONS: This study has, for the first
      time, quantified global incidence patterns of CGC and NCGC providing new insights
      into the global burden of these cancers. Country-specific estimates are provided;
      however, these should be interpreted with caution. This work will support future
      investigations across populations.

PMID- 25748649
TI  - Population-based assessment of the outcomes in patients with postcolonoscopy
      colorectal cancers.
AB  - OBJECTIVE: The potential for cancers to not be detected on colonoscopy is
      increasingly recognised, but little is known about patient outcomes. The
      objective of this study was to assess the outcomes of patients diagnosed with
      postcolonoscopy colorectal cancers (PCCRCs). DESIGN: We conducted a population
      based retrospective cohort study, including all patients diagnosed with
      colorectal cancer (CRC) in Ontario, Canada from 2003 to 2009. Patients were
      categorised into three groups: DETECTED (diagnosed within 6 months of first
      colonoscopy), PCCRC (diagnosed 6-36 months after first colonoscopy) or NOSCOPE
      (no colonoscopy within 36 months of diagnosis). Univariate and multivariable
      analyses were conducted to study overall survival, surgical treatment, emergency
      presentation and surgical complications. RESULTS: Overall, 45 104 patients were
      included, with 2804 being classified as having a PCCRC. Compared with the
      DETECTED group, PCCRC was associated with a significantly higher likelihood of
      stage IV disease (17.2% vs 12.9%), worse overall survival (5 year OS: 60.8% vs
      68.3%, p<0.0001; adjusted HR: 1.25, 95% CI 1.17 to 1.32, p<0.0001), a higher
      likelihood of emergency presentation (OR: 2.86, 95% CI 2.56 to 3.13, p<0.001) and
      lower likelihood of surgical resection (OR: 0.61, 95% CI 0.55 to 0.67, p<0.001).
      However, patients with PCCRC had significantly better outcomes than those in the
      NOSCOPE group (stage IV: 37.1%, 5 year OS: 38.9%) CONCLUSIONS: Compared with CRC
      detected by colonoscopy, PCCRCs are associated with a higher risk of emergent
      presentation, a lower likelihood of surgical resection and most notably,
      significantly worse oncological outcomes. However, they have better outcomes than
      patients with no recent colonoscopy.

PMID- 25748650
TI  - Adapting the drivers to the road: a new strategy for cancer evolution?

PMID- 25748651
TI  - Zygotic genome activation triggers the DNA replication checkpoint at the
      midblastula transition.
AB  - A conserved feature of the midblastula transition (MBT) is a requirement for a
      functional DNA replication checkpoint to coordinate cell-cycle remodeling and
      zygotic genome activation (ZGA). We have investigated what triggers this
      checkpoint during Drosophila embryogenesis. We find that the magnitude of the
      checkpoint scales with the quantity of transcriptionally engaged DNA. Measuring
      RNA polymerase II (Pol II) binding at 20 min intervals over the course of ZGA
      reveals that the checkpoint coincides with widespread de novo recruitment of Pol
      II that precedes and does not require a functional checkpoint. This recruitment
      drives slowing or stalling of DNA replication at transcriptionally engaged loci.
      Reducing Pol II recruitment in zelda mutants both reduces replication stalling
      and bypasses the requirement for a functional checkpoint. This suggests a model
      where the checkpoint functions as a feedback mechanism to remodel the cell cycle
      in response to nascent ZGA.

PMID- 25748652
TI  - Diffusible crosslinkers generate directed forces in microtubule networks.
AB  - Cytoskeletal remodeling is essential to eukaryotic cell division and
      morphogenesis. The mechanical forces driving the restructuring are attributed to
      the action of molecular motors and the dynamics of cytoskeletal filaments, which
      both consume chemical energy. By contrast, non-enzymatic filament crosslinkers
      are regarded as mere friction-generating entities. Here, we experimentally
      demonstrate that diffusible microtubule crosslinkers of the Ase1/PRC1/Map65
      family generate directed microtubule sliding when confined between partially
      overlapping microtubules. The Ase1-generated forces, directly measured by optical
      tweezers to be in the piconewton-range, were sufficient to antagonize motor
      protein driven microtubule sliding. Force generation is quantitatively explained
      by the entropic expansion of confined Ase1 molecules diffusing within the
      microtubule overlaps. The thermal motion of crosslinkers is thus harnessed to
      generate mechanical work analogous to compressed gas propelling a piston in a
      cylinder. As confinement of diffusible proteins is ubiquitous in cells, the
      associated entropic forces are likely of importance for cellular mechanics beyond
      cytoskeletal networks.

PMID- 25748653
TI  - Hypothalamic Agrp neurons drive stereotypic behaviors beyond feeding.
AB  - The nervous system evolved to coordinate flexible goal-directed behaviors by
      integrating interoceptive and sensory information. Hypothalamic Agrp neurons are
      known to be crucial for feeding behavior. Here, however, we show that these
      neurons also orchestrate other complex behaviors in adult mice. Activation of
      Agrp neurons in the absence of food triggers foraging and repetitive behaviors,
      which are reverted by food consumption. These stereotypic behaviors that are
      triggered by Agrp neurons are coupled with decreased anxiety. NPY5 receptor
      signaling is necessary to mediate the repetitive behaviors after Agrp neuron
      activation while having minor effects on feeding. Thus, we have unmasked a
      functional role for Agrp neurons in controlling repetitive behaviors mediated, at
      least in part, by neuropeptidergic signaling. The findings reveal a new set of
      behaviors coupled to the energy homeostasis circuit and suggest potential
      therapeutic avenues for diseases with stereotypic behaviors.

PMID- 25748655
TI  - Canadian society of allergy and clinical immunology annual scientific meeting
      2013.

PMID- 25748654
TI  - Genome-wide CRISPR screen in a mouse model of tumor growth and metastasis.
AB  - Genetic screens are powerful tools for identifying genes responsible for diverse
      phenotypes. Here we describe a genome-wide CRISPR/Cas9-mediated loss-of-function
      screen in tumor growth and metastasis. We mutagenized a non-metastatic mouse
      cancer cell line using a genome-scale library with 67,405 single-guide RNAs
      (sgRNAs). The mutant cell pool rapidly generates metastases when transplanted
      into immunocompromised mice. Enriched sgRNAs in lung metastases and late-stage
      primary tumors were found to target a small set of genes, suggesting that
      specific loss-of-function mutations drive tumor growth and metastasis. Individual
      sgRNAs and a small pool of 624 sgRNAs targeting the top-scoring genes from the
      primary screen dramatically accelerate metastasis. In all of these experiments,
      the effect of mutations on primary tumor growth positively correlates with the
      development of metastases. Our study demonstrates Cas9-based screening as a
      robust method to systematically assay gene phenotypes in cancer evolution in
      vivo.

PMID- 25748656
TI  - Genetic Characterization of a Unique Recombinant Originating from CRF55_01B,
      CRF01_AE, and CRF07_BC in Shenzhen, China.
AB  - Multiple subtypes were found to be epidemic in the Shenzhen men who have sex with
      men (MSM) population, which always predicts the emergence of a unique
      recombinant. In 2012, CRF55_01B was first reported, which later was proven to
      have originated in MSM in Shenzhen city. In this study, we reported a unique
      recombinant form (URF) of HIV-1 identified in a man who has had sex with men in
      Shenzhen city. The strain showed a genomic schematic map similar to CRF55_01B
      with subtype C segments inserted in the gag and pol genes. The full-length genome
      was amplified in two halves with 1-kb overlap regions. The PCR products were
      cloned and sequenced. A recombination detection program showed that two subtype C
      fragments and two subtype B fragments were inserted into the CRF01_AE backbone
      genome in the gag and pol regions. In the phylogenetic tree, the subtype C
      fragments clustered with CRF07_BC variants and the other segments grouped with
      CRF55_01B strains except for one segment that clustered with CRF01_AE. Similar
      breakpoints between our strain and CRF65_cpx were also observed. The data
      suggested that the URF strain might be the recombinant form of CRF55_01B,
      CRF01_AE, and CRF07_BC. This is the first report of a third generation of
      recombination of HIV-1 that originated from CRF55_01B in China. The
      identification of the URF indicated the severity of the HIV epidemic in Shenzhen
      MSM and the urgent need for epidemiological surveillance of the new
      recombination. 

PMID- 25748657
TI  - Fracture healing: fracture healing understood as the result of a fascinating
      cascade of physical and biological interactions. Part II.
AB  - Based on our own observations an explanation of the different factors influencing
      bone reaction is proposed. Special attention is given to the aspect of tissue
      deformation (strain). We propose thinking in terms of strain rather than of
      instability when contemplating tissue reaction. Considering the observed bone
      behavior should help improving the treatment of fractures and their
      complications.

PMID- 25748658
TI  - Management of femoral shaft fractures.
AB  - Femoral shaft fractures are severe injuries and are often associated with a high
      impact trauma mechanism, frequently seen in multiple injured patients. In
      contrast an indirect trauma mechanism can lead to a complex femoral shaft
      fracture especially in elderly patients with minor bone stock quality. Hence
      management of femoral shaft fractures is often directed by co-morbidities,
      additional injuries and the medical condition of the patient. Timing of fracture
      stabilization is depended on the overall medical condition of the patient, but
      definite fracture fixation can often be implemented in the early total care
      concept in management of multiple injured patients. The treatment of choice is
      intramedullary fracture fixation. Further development of existing intramedullary
      nailing systems now offer comfortable handling and different locking options.
      Ipsilateral fractures of the neck and shaft are therefore facilitated in
      management. Then again increasing numbers of obese patient are representing a new
      patient group with challenging co-factors in fracture management. Sufficient
      preoperative planning is helpful to choose the most adequate fixation device.
      Correct reduction of the fracture and perioperative control of the axis and
      rotation is mandatory to avoid postoperative malrotation, which still represents
      the most frequent complication.

PMID- 25748659
TI  - Evidence based postoperative treatment of distal radius fractures following
      internal locking plate fixation.
AB  - Originally, the treatment method of choice for distal radial fractures (DRF) has
      been a non-operative approach with six to eight weeks of plaster casting. The
      introduction of volar locking plate systems at the beginning of the 21 st century
      has pushed trends towards open reduction and internal fixation (ORIF). While the
      introduction of fixed angle locking plates together with the increasing knowledge
      on wrist function and related variable outcomes has led to consensus that
      operative fixation in instable DRF is the treatment method of choice, there is no
      agreement on a postoperative care of these injuries. The authors will discuss the
      available evidence for current concepts of postoperative treatment of DRFs
      following fixed angle fixation under socioeconomical, biomechanical and burden of
      disease aspects. Further, relevant randomized controlled trials are evaluated
      with regard to applied postoperative treatment regimes and related risks for
      complications.

PMID- 25748660
TI  - [Minimally invasive stabilization of posterior pelvic ring injuries with a
      transiliac internal fixator and two iliosacral screws: comparison of outcome].
AB  - PURPOSE OF THE STUDY: A comparison of radiological and clinical results between
      dorsal pelvic segment stabilization with a transiliac internal fixator (TIFI) and
      that with two iliosacral screws (IS). MATERIAL AND METHODS: In this prospective
      study, both the TIFI and the IS group had 32 patients. The majority of injuries
      were assessed as type C1.3 because only patients with a high-energy mechanism of
      injury were included. Radiological results were evaluated according to the Matta
      scoring system and clinical outcome using the Majeed score and the Pelvic Outcome
      Score. Categorical data were evaluated by the two-sided Fisher's exact test or
      Pearson's chi2 test and continuous data by Student's t-test. A test result with
      p<0.05 was considered statistically significant. RESULTS: In the TIFI group, the
      mean posterior displacement was 2.2 mm, in the IS group it was 1.9 mm
      (p=0.58542). The pelvic outcome scores in the TIFI group were: excellent, 28%;
      good, 12%; fair, 48.0%; and poor, 4 %; in the IS group they were: excellent,
      11.1%; good, 22.2%; fair, 66.7%; and poor, 0.0% (p=0.51731). The Majeed scores
      were as follows: excellent, 56.0%; good, 16.0%; fair, 20.0%; poor 8.0 % for the
      TIFI group and excellent, 50.0%; good, 27.8%; fair, 11.1%; and poor, 11.1% for
      the IS group (p=0.70187). Within the total, average Majeed score was 80.64 points
      in TIFI, 80.67 in IS (p=0.99654). In a sub-analysis of unilateral transforaminal
      fractures (Pohlemann type II), the average score for TIFI was 82.8 points and
      only 53.5 points for IS; the differences were statistically significant
      (p=0.04517). No intraoperative complications were associated with TIFI and one
      injury to the superior gluteal artery (3.1%) and two iatrogenic neurological
      injuries with IS (6.3%; p=0.23810). In the TIFI group, the fixator was removed
      without complications. In the IS group, post-operative wound bleeding following
      screw removal occurred in three patients (20.0%; p=0.22414), complete extraction
      of screws and washers was successful only in seven patients (46.7%), washers were
      left in situ in six patients (40.0 %) and IS removal was not possible in two
      patients (13.3%). The difference in complications between the groups was highly
      significant (p=0.00220). DISCUSSION: The results of our study are in agreement
      with those of the relevant studies published recently as well as with the
      outcomes of transiliac plate fixation reported in the literature. TIFI
      implantation is preferred in transforaminal and central sacral fractures because,
      unlike iliosacral screws, it carries a low risk of excessive compression of the
      sacral foramina and iatrogenic neurological injury. There were no significant
      differences in clinical and radiological findings between TIFI and IS procedures.
      Only in unilateral transforaminal fracture the TIFI stabilization had better
      outcome, as shown by the Majeed score. The IS fixation was associated with a
      higher rate of complications not only in primary implantation, but also at
      implant removal. CONCLUSIONS: The TIFI technique is superior to the IS procedure
      in fixation of unilateral transforaminal fractures and provides a reasonable
      alternative to the existing types of minimally invasive fixation.

PMID- 25748661
TI  - [Risk of bleeding from the internal iliac artery and its branches in pelvic
      fractures: cadaver study].
AB  - PURPOSE OF THE STUDY: The study was designed to investigate whether anatomical
      variations of the anterior and posterior divisions of the internal iliac artery
      and their branches are associated with different risks of bleeding resulting from
      injury to the posterior pelvic segment. MATERIAL AND METHODS: The study was
      carried out on 19 cadavers. The dissected area included the internal iliac artery
      from the common iliac artery bifurcation to the origins of the superior gluteal
      artery, the inferior gluteal artery and the internal pudendal artery. Using an
      electronic slide rule, distances between the bifurcation and the origin of each
      branch from either the anterior or the posterior division were measured. The
      diameter of each vessel was also determined. Findings of the study were compared
      with variations described in the literature. The degree of risk for bleeding
      related to different anatomical variations of the internal iliac artery and its
      branches was evaluated based on the proximity to the bone. RESULTS: There are six
      anatomical variations of internal iliac artery branches. Four of them were found:
      type A1 was recorded in 10 specimens, type A2 in six, type B1 in two and type C
      in one specimen. Types B2 and D were not seen. DISCUSSION: The type B2 and C
      anatomical variations were considered to carry higher risks of bleeding due to
      injury to the posterior pelvic segment. These variations are characterized by
      vessels larger in diameter and a longer course of the posterior division along
      the posterior part of the greater sciatic notch (area often involved in unstable
      pelvic ring fractures). On the other hand, the type C variation showed a longer
      internal iliac artery separated from the bone with a thick layer of soft tissue,
      which suggested lower risk than was attributed to the dominant type A1 variation.
      It was not possible to evaluate type B2 variation because it is very rare and was
      not found in study material. In type A2 and B1 variations, the branches were
      separated from bony structures similarly to the dominant type A1 variation.
      CONCLUSIONS: The cadaver study designed to assess the risk of bleeding associated
      with different morphological variations of the branching pattern of the internal
      iliac artery did not identify any anatomical arrangement that might carry a
      higher risk of injury to the vessels by free bone fragments of the posterior
      segment in unstable pelvic fractures. It can be concluded that less common
      branching patterns of the internal iliac artery are not associated with higher
      risk of bleeding than the dominant type A1 variation.

PMID- 25748662
TI  - [Conservative treatment of acetabular fractures: epidemiology and medium-term
      clinical and radiological results].
AB  - PURPOSE OF THE STUDY: The vast majority of studies on fractures of the acetabulum
      are concerned with surgical treatment. All displaced fractures are presented as
      surgically treated. The purpose of this study was to evaluate the results of
      surgical and conservative treatment of patients with acetabular fractures in
      relation to the degree of fracture displacement. MATERIAL AND METHODS: We
      analysed 140 fractures of the acetabulum treated in our institution by different
      methods between 2009 and 2013. In addition to the use of Letournel's
      classification, we allocated each fracture to one of six groups: 1. Sixty
      displaced fractures treated surgically, 2. Twenty three fractures with a
      displacement of more than 6 mm, 3. Eighteen slightly displaced fractures (2-3 mm
      in the acetabular roof or 4-5 mm in other parts of the acetabulum), 4. Twenty non
      displaced fractures, 5. Six pelvic fractures involving the acetabulum and 6.
      Thirteen fractures of old people, mostly displaced but not examined by CT. Groups
      2 to 6 were treated conservatively. In all patients, demographic and
      epidemiologic factors were analysed in relation to the patient's group
      assignment. In 107 patients, hip function was assessed using the Matta clinical
      grading system at a minimum follow-up of 12 months (average 3.16 years).
      Radiological status, time of admission, start of weight-bearing after the
      accident, working ability, mortality and complications were also evaluated.
      RESULTS: Non-displaced fractures were often associated with serious injury or
      polytrauma in 20 patients; not all of them had excellent functional outcome.
      (mean score, 17.25). Excluding two patients who developed avascular necrosis,
      fourteen slightly displaced fractures had a fixal score of 16.92. Sixteen
      patients with displaced fractures were managed conservatively due to their poor
      medical condition and other circumstances. Their functional outcome (mean score,
      15.25) was significantly worse than that of the patients with non-displaced
      fractures (p=0.02) and worse than the outcome in patients with slightly displaced
      fractures, but the difference was not significant (p=0.32). No occurrence of
      accelerated post-traumatic arthritis was observed in these groups. The mean
      clinical score of 14.80 and 60% of excellent and good results were achieved in
      surgically treated patients. Eight of them were treated by primary hip
      arthroplasty and osteosynthesis. A total of 11 patients required total hip
      arthroplasty because of post-traumatic osteoarthritis, but only one from the
      group of slightly displaced fractures, all others from the group of surgically
      treated patients. DISCUSSION: Displaced fractures of the acetabulum are best
      treated by open reduction and internal fixation. The type of fracture and the
      quality of reduction influence the functional outcome. There are a few studies
      reporting long-term outcomes in conservatively treated acetabular fractures.
      Although conservative treatment continues to be the mainstay of treatment in most
      centres in the developing countries, it is obvious that not all of acetabular
      fractures can or must be treated surgically or identically. We found that, in
      many cases, surgery was too dangerous for the patient and his/her medical
      condition or that the result of surgery was doubtful, mostly because of a late
      presentation. In some cases, primary hip arthroplasty is a solution. Secondary
      total hip replacement is technically more demanding and has a higher rate of
      failure. CONCLUSIONS: Conservative treatment is the method of choice for the
      treatment of non-displaced acetabular fractures. Excellent or very good results
      can also be expected in slightly displaced fractures if acetabular roof
      involvement is minor. In displaced fractures, if the result of surgery is
      doubtful under various circumstances or if high-risk medical conditions are
      present in the patient, conservative treatment can be the method of choice with
      satisfying results. Key words: acetabular fractures, conservative treatment,
      degree of displacement, epidemiology of acetabular fractures.

PMID- 25748663
TI  - [The incidence of osteopenia and osteoporosis in patients with cementless total
      hip arthroplasty].
AB  - PURPOSE OF THE STUDY: The aim of the study was to evaluate the incidence of
      osteopenia and osteoporosis in the patients elected to cementless total hip
      replacement. MATERIAL AND METHODS: The group evaluated comprised 100 patients
      with primary or secondary forms of coxarthrosis who underwent cementless total
      hip arthroplasty (THA). The results of densitometric examination of the lumbar
      spine and proximal femur were analysed. Based on the lowest T-score value, the
      patients were divided into three groups, i.e., fist, normal bone density; second,
      osteopenia; third, osteoporosis. Clinical examination included patient medical
      history, Harris hip scores and visual analogue scale assessment for pain
      intensity; the Kellgren-Lawrence classification was used to measure the grade of
      hip osteoarthritis; blood tests were made to assess the levels of total calcium,
      ionised calcium, phosphorus, vitamin D and the markers of bone resorption and
      formation. RESULTS: Osteoporosis was found in 32 and osteopenia in 21 patients;
      47 patients had normal bone density. Osteoporosis was detected in the lumbar
      spine of 21 patients, in the proximal femur of nine patients and at both sites in
      two patients. In 13 patients this diagnosis was made for the fist time. The
      patients with osteoporosis had a significantly lower body mass index. There were
      no differences in the other characteristics, i.e., age, functional, radiological
      and laboratory findings, among the groups; all three showed the mean vitamin D
      concentration below the lowest level of its physiological range. Insufficient
      vitamin D levels were found in 54 women and 18 men. Of all patients, only 13
      women and four men took vitamin D supplements. DISCUSSION Osteoarthritis and
      osteoporosis are the most frequent complex musculoskeletal diseases. Several
      studies have suggested that these disorders are mutually exclusive. This
      assumption has been based on the absence of radiographic evidence of
      osteoarthritis seen in many elderly patients with femoral neck fractures. Our
      relatively frequent findings of osteopenia and osteoporosis in this study show
      that patients with osteoarthritis may not be protected from the development of
      generalised osteoporosis. Our results are compared with the relevant literature
      data and potential effects of osteoporosis and vitamin D deficiency on total hip
      arthroplasty are discussed. CONCLUSIONS: Hip osteoarthritis does not reduce the
      risk of generalised osteoporosis. We found a relative high incidence of
      osteopenia and osteoporosis as well as vitamin D deficiency in patient with
      advanced form of hip osteoarthritis.

PMID- 25748664
TI  - [Low expression of Tlr-1, -2, -4 a il-2, -2r, -10, -10r and TgFb1 in
      pseudosynovial tissue collected at revision total knee arthroplasty for aseptic
      loosening].
AB  - PURPOSE OF THE STUDY: Aseptic loosening (AL) and periprosthetic osteolysis (PPOL)
      in total hip (THA) and knee (TKA) arthroplasty are linked to an inflammatory
      process initiated by wear debris released from artificial joints. There is still
      limited information about the contribution of Toll-like receptors (TLRs) and
      distinct regulatory cytokines to AL/PPOL in both joints. METHODS: In this study,
      we investigated mRNA expression of TLR-1,-2,-4 and cytokines/receptors (IL-2,-2R,
      10,-10R, TGFb1) in pseudosynovial tissue obtained from 55 patients with
      aseptically failed THAs/TKAs and 37 control patients with hip/knee primary
      osteoarthritis (OA) using quantitative RT-PCR. Immunohistochemical staining was
      used to detect the corresponding proteins. Non-parametric Kruskal-Wallis and Mann
      Whitney tests were used to determine differences between the patient groups.
      RESULTS: When comparing expression profiles between patients with aseptically
      failed THA and TKA, higher amounts of TLR-1,- 2,-4 and IL-2R mRNA transcripts
      were detected in THA patients. The mRNA expression of studied molecules (TLR-1,
      2,-4, IL-2, IL-10, IL-2R, IL-10R, TGFb1) did not differ between THA and OA hip
      tissues. Lower mRNA expression of TLR-1,-2,- 4, IL-10, and IL-10R was detected in
      TKA when compared to control knee OA. Similar mRNA profiles of IL-2, IL-2R, and
      TGFb1 were observed in TKA and knee OA. Using immunohistochemistry, we detected
      low expression of TLR-1 protein in failed THA/TKA, whereas TLR-2 protein levels
      were higher in TKA/THA patients than in OA controls. High individual variability
      in TLR-4 protein levels was detected among patients with aseptically loosened THA
      and TKA. IL-10 protein levels were similar in THA and TKA patient subgroups and
      control subjects, whereas IL-10R protein level was higher in failed TKAs and OA
      controls than in THAs. No difference in IL-2 protein levels was detected between
      patients with THA/TKA and those with OA. DISCUSSION: Our data indicate close
      similarity between the expression patterns in aseptically failed THA and TKA.
      However, certain differences were observed which also suggest unique pathways
      associated with the end-stage of aseptic loosening in THA and TKA. For instance,
      differences in the size, shape and load of polyethylene particles between THA and
      TKA could play some role. The composition of THA and TKA and differences in terms
      of mechanical forces might also be involved. CONCLUSIONS: This is the fist study
      comparing the gene expression profile of a particular set of innate immunity
      regulatory molecules between tissues from aseptically failed THA and TKA. Low
      expression of TLR-1,-2,-4 and cytokines/receptors (IL-2, IL-2R, IL-10, IL-10R,
      and TGFb1) was observed in pseudosynovial tissues obtained from aseptically
      failed THAs and TKAs. Higher amount of TLR transcripts was detected in THA as
      compared to TKA. These findings indicate certain differences in the mechanism of
      aseptic loosening occurring at the site of THA and TKA. Further research is
      warranted.

PMID- 25748665
TI  - [Sternal fractures and their surgical treatment].
AB  - PURPOSE OF THE STUDY: Sternal fractures occur most frequently in vehicle
      accidents, then due to falls from a height and by other blunt chest trauma. Most
      of these injuries are simple, non-displaced fractures only rarely requiring
      surgical management. Based on a retrospective analysis, the authors present their
      experience with the treatment of sternal fractures, emphasizing the use of
      osteosynthesis. MATERIAL AND METHODS: A group of 293 patients treated for fresh
      sternal fractures in the period from 2004 to 2013 were evaluated. Their median
      age was 47.5 years (range, 2 to 86 years). They were allocated to two groups
      according to the method of treatment, ie., conservative versus surgical. The two
      groups were compared in the following characteristics: mechanism and extent of
      trauma, methods of treating the fracture and associated injuries and troponin-T
      and myoglobin values. RESULTS: Of the 293 patients, 16 had surgery (surgical
      group) and the remaining patients were treated conservatively. Eleven patients
      (3.8%) had surgery for instability or chest wall deformity. Five patients (1.7%)
      underwent urgent cardiovascular surgery due to complications of sternum fracture.
      In the surgical group, comminuted fractures were more frequent (p=0.0003), rib
      fractures had a higher incidence rate (p=0.0442), concomitant abdominal injuries
      occurred more often (p=0.0173) and serum levels of troponin-T and myoglobin were
      higher (p<0.0001 and p=0.0114, respectively) than in the other group. DISCUSSION:
      The majority of sternal injuries (90-95%) are non-displaced, simple fractures
      that heal spontaneously. In complicated fractures, reduction and fragment
      fixation relieve pain, provide prevention from respiratory complications and make
      the duration of mechanical ventilation shorter. Our results show that
      osteosynthesis was mostly indicated in displaced and comminuted fractures or
      severe chest deformity. Concomitant intra-abdominal injury is caused by a flexion
      mechanism or an impact on the front of the body. Serious sternal fractures are
      associated with increased serum levels of troponin-T and myoglobin. CONCLUSIONS:
      Plate fixation is a suitable method of stable osteosynthesis in complicated
      sternal fractures. It shortens the duration of mechanical ventilation and repairs
      post-traumatic chest wall deformities.

PMID- 25748666
TI  - [Open talar dislocation].
AB  - PURPOSE OF THE STUDY: Total talar extrusion is a rare injury. It is frequently
      associated with severe soft tissue injury. There is no consensus about an
      appropriate treatment for an extruded talus. Total extrusion of the talus has a
      high possibility of avascular necrosis of the talus or infection. The primary
      goal of this study is a retrospective evaluation of the patients with open total
      talar dislocation treated by immediate reimplantation. MATERIALS AND METHODS: We
      evaluated six patients (mean age, 29.6 years) with an open total talar
      dislocation treated in the Traumatological Hospital Brno. The dislocated talus,
      after debridement, was reduced, held in the correct position by Kirschner wires
      and spanned by external fixation, with two pins placed in the calcaneus and two
      in the distal tibia. The patients were evaluated on the basis of clinical and
      radiographic examination. Two patients underwent secondary reconstruction
      procedures. The four remaining patients were evaluated using the AOFAS score.
      RESULTS: The mean follow-up period was 24.2 months (range, 18-32). Two patients
      had an infection and one developed avascular necrosis of the talus. One patient
      required arthrodesis of the subtalar joint and one talectomy with tibiocalcaneal
      arthrodesis and callus distraction of the tibia. CONCLUSIONS: A primary
      reimplantation of the talus can produce good functional outcome. It is reasonable
      to replace an extruded talus as soon as possible after debridement. Infection and
      avascular necrosis of the talus seem to be difficult to predict.

PMID- 25748667
TI  - Total knee arthroplasty in patient with paraplegia after spinal cord injury.
AB  - The clinical management of paraplegic patients is more complex than in able
      bodied subjects. Spinal cord injury (SCI) affects younger, active people more
      often than the elderly during high-energy fall or traffic accidents. In order to
      return to work after suffering an SCI, patients need to regain their functional
      independence, especially their ability to drive. The literature lacks strong
      evidence addressing the surgical solutions in severe knee arthrosis in paralyzed
      patients after SCI. We present a favourable outcome of total knee arthroplasty
      (TKA) of a stiff knee in extension in a man with T12 grade C paraplegia after
      SCI. We describe an effective rehabilitation protocol after knee arthroplasty in
      patient with damage to the spinal cord. Several factors should be taken into
      account before performing surgery: 1. ability of regaining some of spinal cord
      locomotor function through intensive gait rehabilitation in SCI patients, 2.
      presence of muscle imbalance and knee contractures combined with a risk of bone
      fracture resulting from intensive postoperative rehabilitation, 3. the impaired
      microvasculature of the skin and subcutaneous tissues and increased risk of
      occlusion occurrence of the capillaries and small vessels of the leg, 4. higher
      prevalence of secondary infections via urinary entry sites in patients after SCI,
      5. patient's strong determination and willingness to undergo the arthroplasty
      procedure. TKA might be considered in selected paralyzed patients after SCI,
      especially in those with severe arthrosis as well as significant knee
      contractures. Our study reveals the advantage of performing TKA in improving
      functional state in patients with cord injury.

PMID- 25748668
TI  - Using HIV surveillance registry data to re-link persons to care: the RSVP Project
      in San Francisco.
AB  - BACKGROUND: Persons with unsuppressed HIV viral load (VL) who disengage from care
      may experience poor clinical outcomes and potentially transmit HIV. We assessed
      the feasibility and yield of using the San Francisco Department of Public Health
      (SFDPH) enhanced HIV surveillance system (eHARS) to identify and re-engage such
      persons in care. METHODS: Using SFDPH eHARS data as of 4/20/2012 (index date), we
      selected HIV-infected adults who were alive, had no reported VL or CD4 cell count
      results in the past nine months (proxy for "out-of-care") and a VL >200 copies/mL
      drawn nine to 15 months earlier. We prioritized cases residing locally for
      investigation, and used information from eHARS and medical and public health
      databases to contact them for interview and referral to the SFDPH linkage
      services (LINCS). Twelve months later, we matched-back to eHARS data to assess
      how HIV laboratory reporting delays affected original eligibility, and if persons
      had any HIV laboratory results performed and reported within 12 months after
      index date ('new labs'). RESULTS: Among 434 eligible persons, 282 were
      prioritized for investigation, of whom 75 (27%) were interviewed, 79 (28%) could
      not be located, and 48 (17%) were located out of the area. Among the interviewed,
      54 (72%) persons accepted referral to LINCS. Upon match-back to eHARS data, 324
      (75%) in total were confirmed as eligible, including 221 (78%) of the
      investigated; most had new labs. CONCLUSIONS: Among the investigated persons
      presumed out-of-care, we interviewed and offered LINCS referral to about one
      quarter, demonstrating the feasibility but limited yield of our project. Matching
      to updated surveillance data revealed that a substantial minority did not
      disengage from care and that most re-engaged in HIV care. Verifying persons' HIV
      care status with medical providers and improving timeliness of transfer and cross
      jurisdictional sharing of HIV laboratory data may aid future efforts.

PMID- 25748669
TI  - Developmental bisphenol A (BPA) exposure leads to sex-specific modification of
      hepatic gene expression and epigenome at birth that may exacerbate high-fat diet
      induced hepatic steatosis.
AB  - Developmental bisphenol A (BPA) exposure increases adulthood hepatic steatosis
      with reduced mitochondrial function. To investigate the potential epigenetic
      mechanisms behind developmental BPA-induced hepatic steatosis, pregnant Sprague
      Dawley rats were dosed with vehicle (oil) or BPA (100MUg/kg/day) from gestational
      day 6 until postnatal day (PND) 21. After weaning, offspring were either
      challenged with a high-fat (HF; 45% fat) or remained on a control (C) diet until
      PND110. From PND60 to 90, both BPA and HF diet increased the fat/lean ratio in
      males only, and the combination of BPA and HF diet appeared to cause the highest
      ratio. On PND110, Oil-HF, BPA-C, and BPA-HF males had higher hepatic lipid
      accumulation than Oil-C, with microvesicular steatosis being marked in the BPA-HF
      group. Furthermore, on PND1, BPA increased and modified hepatic triglyceride (TG)
      and free fatty acid (FFA) compositions in males only. In PND1 males, BPA
      increased hepatic expression of FFA uptake gene Fat/Cd36, and decreased the
      expression of TG synthesis- and beta-oxidation-related genes (Dgat, Agpat6,
      Cebpalpha, Cebpbeta, Pck1, Acox1, Cpt1a, Cybb). BPA altered DNA methylation and
      histone marks (H3Ac, H4Ac, H3Me2K4, H3Me3K36), and decreased the binding of
      several transcription factors (Pol II, C/EBPbeta, SREBP1) within the male Cpt1a
      gene, the key beta-oxidation enzyme. In PND1 females, BPA only increased the
      expression of genes involved in FFA uptake and TG synthesis (Lpl, Fasn, and
      Dgat). These data suggest that developmental BPA exposure alters and reprograms
      hepatic beta-oxidation capacity in males, potentially through the epigenetic
      regulation of genes, and further alters the response to a HF diet. 

PMID- 25748670
TI  - Colour parameters and shade correspondence of CAD-CAM ceramic systems.
AB  - OBJECTIVES: To evaluate colour differences between (1) CAD-CAM ceramic systems
      considering shades A1, A2 and A3 and the corresponding nominal shade of VC (Vita
      Classical shade guide) and (2) shades A1-A2, A2-A3 and A1, A2 and A3 within the
      same ceramic system. METHODS: Samples of shades A1, A2 and A3 were fabricated
      (n=5) from CAD-CAM ceramic blocks (IPS e.max((r)) CAD LT and HT, IPS Empress((r))
      CAD LT and HT, ParadigmTM C, and VITABLOCS((r)) Mark II) and polished to 1.0+/
      0.01mm in thickness. Spectral reflectance and colour coordinates were measured
      using a spectroradiometer inside a viewing booth using the CIE D65 illuminant and
      the d/0 degrees  geometry. Spectral reflectance curves were compared using VAF
      coefficient and were statistically analyzed using Kruskal-Wallis and the Mann
      Whitney U test (alpha=0.05). Colour coordinates were statistically analyzed using
      one-way ANOVA, Tukey's test with Bonferroni correction (alpha=0.001). All colour
      differences (DeltaEab(*) and DeltaE00) were analyzed through comparisons with the
      PT - perceptibility and AT - acceptability thresholds for dental ceramics.
      RESULTS: DeltaE between ceramic systems and its corresponding shade ranged from
      6.32 to 13.42 (DeltaEab(*)) and 4.48 to 9.30 (DeltaE00). DeltaE between shades A1
      A2, A2-A3 and A1, A2 and A3 ranged, respectively, 1.93-4.82, 1.22-5.59 and 3.63
      8.84 (DeltaEab(*)); 1.54-3.87, 1.03-3.90 and 2.95-6.51 (DeltaE00). CONCLUSIONS:
      Considering the corresponding nominal shade from VC, none of the ceramic systems
      showed colour differences below the AT. In addition, some ceramic systems showed
      colour differences below AT (shades A1-A2 and A2-A3) and below PT (shades A2-A3).
      CLINICAL SIGNIFICANCE: Careful adjustments should be made to the final shade of
      CAD-CAM ceramic restorations to reach a clinically acceptable shade match.

PMID- 25748672
TI  - Extraction of SelectSecure leads compared to conventional pacing leads in
      patients with congenital heart disease and congenital atrioventricular block.
AB  - BACKGROUND: SelectSecureTM pacing leads (Medtronic Inc) are increasingly being
      used in pediatric patients and adults with structural congenital heart disease.
      The 4Fr lead is ideal for patients who may require lifelong pacing and can be
      advantageous for patients with complex anatomy. OBJECTIVE: The purpose of this
      study was to compare the extraction of SelectSecure leads with conventional
      (stylette-driven) pacing leads in patients with structural congenital heart
      disease and congenital atrioventricular block. METHODS: The data on lead
      extractions from pediatric and adult congenital heart disease (ACHD) patients
      from August 2004 to July 2014 at Bristol Royal Hospital for Children and the
      Bristol Heart Institute were reviewed. Multivariable regression analysis was used
      to determine whether conventional pacing leads were associated with a more
      difficult extraction process. RESULTS: A total of 57 patients underwent pacemaker
      lead extractions (22 SelectSecure, 35 conventional). No deaths occurred. Mean age
      at the time of extraction was 17.6 +/- 10.5 years, mean weight was 47 +/- 18 kg,
      and mean lead age was 5.6 +/- 2.6 years (range 1-11 years). Complex extraction
      (partial extraction/femoral extraction) was more common in patients with
      conventional pacing leads at univariate (P < .01) and multivariate (P = .04)
      levels. Lead age was also a significant predictor of complex extraction (P <
      .01). CONCLUSION: SelectSecure leads can be successfully extracted using
      techniques that are used for conventional pacing leads. They are less likely to
      be partially extracted and are less likely to require extraction using a femoral
      approach compared with conventional pacing leads.

PMID- 25748671
TI  - Immediate human pulp response to ethanol-wet bonding technique.
AB  - OBJECTIVES: To evaluate the short-term response of human pulps to ethanol-wet
      bonding technique. METHODS: Deep class V cavities were prepared on 17 sound
      premolars and divided into three groups. After acid-etching, the cavities from
      groups 1 (G1) and 2 (G2) were filled with 100% ethanol or distilled water,
      respectively, for 60 s before the application of Single Bond 2. In group 3 (G3,
      control), the cavity floor was lined with calcium hydroxide before etching and
      bonding. All cavities were restored with resin composite. Two teeth were used as
      intact control. The teeth were extracted 48h after the clinical procedures. From
      each tooth serial sections were obtained and stained with haematoxylin and eosin
      (H/E) and Masson's trichrome. Bacteria microleakage was assessed using Brown &
      Brenn. All sections were blindly evaluated for five histological features.
      RESULTS: Mean remaining dentine thickness was 463+/-65MUm (G1); 425+/-184MUm
      (G2); and 348+/-194MUm (G3). Similar pulp reactions followed ethanol- or water
      wet bonding techniques. Slight inflammatory responses and disruption of the
      odontoblast layer related to the cavity floor were seen in all groups. Stained
      bacteria were not detected in any cavities. Normal pulp tissue was observed in G3
      except for one case. CONCLUSIONS: After 48h, ethanol-wet bonding does not
      increase pulpal damage compared to water-wet bonding technique. CLINICAL
      SIGNIFICANCE: Ethanol-wet bonding may increase resin-dentine bond durability.
      This study reported the in vivo response of human pulp tissue when 100% ethanol
      was applied previously to an etch-and-rinse simplified adhesive system.

PMID- 25748673
TI  - Neuronally released vasoactive intestinal polypeptide alters atrial
      electrophysiological properties and may promote atrial fibrillation.
AB  - BACKGROUND: Vagal hyperactivity promotes atrial fibrillation (AF), which has been
      almost exclusively attributed to acetylcholine. Vasoactive intestinal polypeptide
      (VIP) and acetylcholine are neurotransmitters co-released during vagal
      stimulation. Exogenous VIP has been shown to promote AF by shortening action
      potential duration (APD), increasing APD spatial heterogeneity, and causing intra
      atrial conduction block. OBJECTIVE: The purpose of this study was to investigate
      the effects of neuronally released VIP on atrial electrophysiologic properties
      during vagal stimulation. METHODS: We used a specific VIP antagonist (H9935) to
      uncover the effects of endogenous VIP released during vagal stimulation in canine
      hearts. RESULTS: H9935 significantly attenuated (1) the vagally induced
      shortening of atrial effective refractory period and widening of atrial
      vulnerability window during stimulation of cervical vagosympathetic trunks (VCNS)
      and (2) vagal effects on APD during stimulation through fat-pad ganglion plexus
      (VGPS). Atropine completely abolished these vagal effects during VCNS and VGPS.
      In contrast, VGPS-induced slowing of local conduction velocity was completely
      abolished by either VIP antagonist or atropine. In pacing-induced AF during VGPS,
      maximal dominant frequencies and their spatial gradients were reduced
      significantly by H9935 and, more pronouncedly, by atropine. Furthermore, VIP
      release in the atria during vagal stimulation was inhibited by atropine, which
      may account for the concealment of VIP effects with muscarinic blockade.
      CONCLUSION: Neuronally released VIP contributes to vagal effects on atrial
      electrophysiologic properties and affects the pathophysiology of vagally induced
      AF. Neuronal release of VIP in the atria is inhibited by muscarinic blockade, a
      novel mechanism by which VIP effects are concealed by atropine during vagal
      stimulation.

PMID- 25748674
TI  - In vivo electromechanical assessment of heart failure patients with prolonged QRS
      duration.
AB  - BACKGROUND: Combined measurement of electrical activation and mechanical
      dyssynchrony in heart failure (HF) patients is scarce but may contain important
      mechanistic and diagnostic clues. OBJECTIVE: The purpose of this study was to
      characterize the electromechanical (EM) coupling in HF patients with prolonged
      QRS duration. METHODS: Ten patients with QRS width >120 ms underwent left
      ventricular (LV) electroanatomic contact mapping using the Noga(r) XP system
      (Biosense Webster). Recorded voltages during the cardiac cycle were converted to
      maps of depolarization time (TD). Electrode positions were tracked and converted
      into maps of time-to-peak shortening (TPS) using custom-made deformation analysis
      software. Correlation analysis was performed between the 2 maps to quantify EM
      coupling. Simulations with the CircAdapt cardiovascular system model were
      performed to mechanistically unravel the observed relation between TD and TPS.
      RESULTS: The delay between earliest LV electrical activation and peak shortening
      differed considerably between patients (TPSmin-TDmin = 360 +/- 73 ms). On
      average, total mechanical dyssynchrony exceeded total electrical activation
      (DeltaTPS = 177 +/- 47 ms vs DeltaTD = 93 +/- 24 ms, P <.001), but a large
      interpatient variability was observed. The TD and TPS maps correlated strongly in
      all patients (median R = 0.87, P <.001). These correlations were similar for
      regions with unipolar voltages above and below 6mV (Mann-Whitney U test, P =
      .93). Computer simulations revealed that increased passive myocardial stiffness
      decreases DeltaTPS relative to DeltaTD and that lower contractility predominantly
      increases TPSmin-TDmin. CONCLUSION: EM coupling in HF patients is maintained, but
      the relationship between TD and TPS differs strongly between patients. Intra
      individual and inter-individual differences may be explained by local and global
      differences in passive and contractile myocardial properties.

PMID- 25748675
TI  - Night darkness-day light and arrhythmogenesis.

PMID- 25748676
TI  - Platelet Rho GTPases-a focus on novel players, roles and relationships.
AB  - Rho GTPases are critical for platelet function. Although the roles of RhoA, Rac
      and Cdc42 are characterized, platelets express other Rho GTPases, whose
      activities are less well understood. This review summarizes our understanding of
      the roles of platelet Rho GTPases and focuses particularly on the functions of
      Rif and RhoG. In human platelets, Rif interacts with cytoskeleton regulators
      including formins mDia1 and mDia3, whereas RhoG binds SNARE-complex proteins and
      cytoskeletal regulators ELMO and DOCK1. Knockout mouse studies suggest that Rif
      plays no critical functions in platelets, likely due to functional overlap with
      other Rho GTPases. In contrast, RhoG is essential for normal granule secretion
      downstream of the collagen receptor GPVI. The central defect in RhoG-/- platelets
      is reduced dense granule secretion, which impedes integrin activation and
      aggregation and limits platelet recruitment to growing thrombi under shear,
      translating into reduced thrombus formation in vivo. Potential avenues for future
      work on Rho GTPases in platelets are also highlighted, including identification
      of the key regulator for platelet filopodia formation and investigation of the
      role of the many Rho GTPase regulators in platelet function in both health and
      disease. 

PMID- 25748678
TI  - Protein stability versus function: effects of destabilizing missense mutations on
      BRCA1 DNA repair activity.
AB  - Mutations in breast cancer susceptibility gene BRCA1 (breast cancer early-onset
      1) are associated with increased risk of developing breast and ovarian cancers.
      BRCA1 is a large protein of 1863 residues with two small structured domains at
      its termini: a RING domain at the N-terminus and a BRCT (BRCA1 C-terminus domain)
      repeat domain at the C-terminus. Previously, we quantified the effects of
      missense mutations on the thermodynamic stability of the BRCT domains, and we
      showed that many are so destabilizing that the folded functional state is
      drastically depopulated at physiological temperature. In the present study, we
      ask whether and how reduced thermodynamic stability of the isolated BRCT mutants
      translates into loss of function of the full-length protein in the cell. We
      assessed the effects of missense mutants on different stages of BRCA1-mediated
      DNA repair by homologous recombination using chicken lymphoblastoid DT40 cells as
      a model system. We found that all of the mutations, regardless of how profound
      their destabilizing effects, retained some DNA repair activity and thereby
      partially rescued the chicken BRCA1 knockout. By contrast, the mutation R1699L,
      which disrupts the binding of phosphorylated proteins (but which is not
      destabilizing), was completely inactive. It is likely that both protein context
      (location of the BRCT domains at the C-terminus of the large BRCA1 protein) and
      cellular environment (binding partners, molecular chaperones) buffer these
      destabilizing effects such that at least some mutant protein is able to adopt the
      folded functional state. 

PMID- 25748679
TI  - Experimental and theoretical studies on the effects of magnetic fields on the
      arrangement of surface spins and the catalytic activity of Pd nanoparticles.
AB  - Nanocatalysts have very high catalytic activities due to surface atoms with their
      unpaired spins. It is the purpose of this paper to investigate the effect of
      magnetic fields (MFs) on the arrangement of surface spins and their catalytic
      activities. Pd nanoparticles supported on MIL-100(Cr) were selected as catalysts
      for the reduction of 4-nitrophenol under MFs. The result demonstrates that MFs
      can reduce the reaction time from 2.6 to 1.4 min under 0.5 T. This study first
      shows that the configuration of surface spins has an effect on the catalytic
      activity, which can be regulated by a foreign MF. 

PMID- 25748677
TI  - Mitochondrial pyruvate transport: a historical perspective and future research
      directions.
AB  - Pyruvate is the end-product of glycolysis, a major substrate for oxidative
      metabolism, and a branching point for glucose, lactate, fatty acid and amino acid
      synthesis. The mitochondrial enzymes that metabolize pyruvate are physically
      separated from cytosolic pyruvate pools and rely on a membrane transport system
      to shuttle pyruvate across the impermeable inner mitochondrial membrane (IMM).
      Despite long-standing acceptance that transport of pyruvate into the
      mitochondrial matrix by a carrier-mediated process is required for the bulk of
      its metabolism, it has taken almost 40 years to determine the molecular identity
      of an IMM pyruvate carrier. Our current understanding is that two proteins,
      mitochondrial pyruvate carriers MPC1 and MPC2, form a hetero-oligomeric complex
      in the IMM to facilitate pyruvate transport. This step is required for
      mitochondrial pyruvate oxidation and carboxylation-critical reactions in
      intermediary metabolism that are dysregulated in several common diseases. The
      identification of these transporter constituents opens the door to the
      identification of novel compounds that modulate MPC activity, with potential
      utility for treating diabetes, cardiovascular disease, cancer, neurodegenerative
      diseases, and other common causes of morbidity and mortality. The purpose of the
      present review is to detail the historical, current and future research
      investigations concerning mitochondrial pyruvate transport, and discuss the
      possible consequences of altered pyruvate transport in various metabolic tissues.

PMID- 25748680
TI  - Molecular effects of lithium are partially mimicked by inositol-monophosphatase
      (IMPA)1 knockout mice in a brain region-dependent manner.
AB  - We have previously shown that homozygote knockout (KO) of inositol
      monophosphatase1 (IMPA1) results in lithium (Li)-like behavior. We now aimed to
      find out whether Li-treated mice and IMPA1 KO mice exhibit neurochemical
      similarity at the gene- and protein-expression level. Hippocampal and frontal
      cortex B-cell lymphoma (Bcl-2), Bcl-2-associated X protein (BAX), P53, Perodoxin2
      (PRDX2), myristoylated alanine-rich C kinase substrate (MARCKS) and neuropeptide
      Y (NPY) mRNA levels, and hippocampal, frontal cortex and hypothalamic cytokine
      levels, all previously reported to be affected by lithium treatment, were
      measured in three groups of mice: wildtype (WT) on regular-food (RF), WT on Li
      supplemented food (Li-treated) and IMPA1-KOs. Hippocampal and frontal cortex Bcl
      2 and MARCKS were the only genes commonly affected (downregulated) by Li and
      IMPA1 KO; Bcl-2 - by 28% and 19%, respectively; MARCKS - by about 20% in both
      regions. The effect of Li and of IMPA1 KO on cytokine levels differed among the
      three brain areas studied. Only in the hippocampus both interventions exerted
      similar effects. Frontal cortex cytokine levels were unaffected neither by Li nor
      by IMPA1 KO. Similar changes in Bcl-2 and MARCKS but not in PRDX2 and NPY
      following both Li-treatment and IMPA1 KO suggest a mechanism different than
      inositol-monophosphatase1 inhibition for Li's effect on the latter genes. The
      cytokine levels results suggest that the mechanism mediating Li's effect on the
      inflammatory system differs among brain regions. Only in the hippocampus the
      results favor the involvement of the phosphatidylinositol (PI) cycle.

PMID- 25748681
TI  - Modeling of human artery tissue with probabilistic approach.
AB  - Accurate modeling of biological soft tissue properties is vital for realistic
      medical simulation. Mechanical response of biological soft tissue always exhibits
      a strong variability due to the complex microstructure and different loading
      conditions. The inhomogeneity in human artery tissue is modeled with a
      computational probabilistic approach by assuming that the instantaneous stress at
      a specific strain varies according to normal distribution. Material parameters of
      the artery tissue which are modeled with a combined logarithmic and polynomial
      energy equation are represented by a statistical function with normal
      distribution. Mean and standard deviation of the material parameters are
      determined using genetic algorithm (GA) and inverse mean-value first-order second
      moment (IMVFOSM) method, respectively. This nondeterministic approach was
      verified using computer simulation based on the Monte-Carlo (MC) method.
      Cumulative distribution function (CDF) of the MC simulation corresponds well with
      that of the experimental stress-strain data and the probabilistic approach is
      further validated using data from other studies. By taking into account the
      inhomogeneous mechanical properties of human biological tissue, the proposed
      method is suitable for realistic virtual simulation as well as an accurate
      computational approach for medical device validation. 

PMID- 25748682
TI  - Monitoring minimal residual disease in children with high-risk relapses of acute
      lymphoblastic leukemia: prognostic relevance of early and late assessment.
AB  - The prognosis for children with high-risk relapsed acute lymphoblastic leukemia
      (ALL) is poor. Here, we assessed the prognostic importance of response during
      induction and consolidation treatment prior to hematopoietic stem cell
      transplantation (HSCT) aiming to evaluate the best time to assess minimal
      residual disease (MRD) for intervention strategies and in future trials in high
      risk ALL relapse patients. Included patients (n=125) were treated uniformly
      according to the ALL-REZ BFM (Berlin-Frankfurt-Munster) 2002 relapse trial
      (median follow-up time=4.8 years). Patients with MRD ?10(-3) after induction
      treatment (76/119, 64%) or immediately preceding HSCT (19/71, 27%) had a
      significantly worse probability of disease-free survival 10 years after relapse
      treatment begin, with 26% (+/-6%) or 23% (+/-7%), respectively, compared with 58%
      (+/-8%) or 48% (+/-7%) for patients with MRD <10(-3). Conventional intensive
      consolidation treatment reduced MRD to <10(-3) before HSCT in 63% of patients,
      whereas MRD remained high or increased in the rest of this patient group. Our
      data support that MRD after induction treatment can be used to quantify the
      activity of different induction treatment strategies in phase II trials. MRD
      persistence at ?10(-3) before HSCT reflects a disease highly resistant to
      conventional intensive chemotherapy and requiring prospective controlled
      investigation of new treatment strategies and drugs. 

PMID- 25748683
TI  - Impact of lenalidomide on immune functions in the setting of maintenance therapy
      for multiple myeloma.

PMID- 25748684
TI  - Membrane lipid rafts, master regulators of hematopoietic stem cell retention in
      bone marrow and their trafficking.
AB  - Cell outer membranes contain glycosphingolipids and protein receptors, which are
      integrated into glycoprotein microdomains, known as lipid rafts, which float
      freely in the membrane bilayer. These structures have an important role in
      assembling signaling molecules (e.g., Rac-1, RhoH and Lyn) together with surface
      receptors, such as the CXCR4 receptor for alpha-chemokine stromal-derived factor
      1, the alpha4beta1-integrin receptor (VLA-4) for vascular cell adhesion molecule
      1 and the c-kit receptor for stem cell factor, which together regulate several
      aspects of hematopoietic stem/progenitor cell (HSPC) biology. Here, we discuss
      the role of lipid raft integrity in the retention and quiescence of normal HSPCs
      in bone marrow niches as well as in regulating HSPC mobilization and homing. We
      will also discuss the pathological consequences of the defect in lipid raft
      integrity seen in paroxysmal nocturnal hemoglobinuria and the emerging evidence
      for the involvement of lipid rafts in hematological malignancies.

PMID- 25748685
TI  - A tale of two siblings: two cases of AML arising from a single pre-leukemic
      DNMT3A mutant clone.

PMID- 25748686
TI  - Efficacy and toxicity of dexamethasone vs methylprednisolone-long-term results in
      more than 1000 patients from the Russian randomized multicentric trial ALL-MB
      2002.

PMID- 25748687
TI  - The immunosuppressive ligands PD-L1 and CD200 are linked in AML T-cell
      immunosuppression: identification of a new immunotherapeutic synapse.

PMID- 25748688
TI  - ZnO-dotted porous ZnS cluster microspheres for high efficient, Pt-free
      photocatalytic hydrogen evolution.
AB  - The Pt-free photocatalytic hydrogen evolution (PHE) has been the focus in the
      photocatalysis field. Here, the ZnO-dotted porous ZnS cluster microsphere (PCMS)
      is designed for high efficient, Pt-free PHE. The PCMS is designed through an easy
      "controlling competitive reaction" strategy by selecting the thiourea as S(2-)
      source and Zn(Ac)2.2H2O as Zn source in ethylene glycol medium. Under suitable
      conditions, one of the PCMS, named PCMS-1, with high SBET specific area of 194
      m(2)g(-1), microsphere size of 100 nm and grain size of 3 nm can be obtained. The
      formation of PCMS is verified by TEM, XAES, XPS, Raman and IR methods.
      Importantly, a series of the experiments and theoretical calculation demonstrate
      that the dotting of ZnO not only makes the photo-generated electrons/hole
      separate efficiently, but also results in the formation of the active catalytic
      sites for PHE. As a result, the PCMS-1 shows the promising activity up to 367
      MUmol h(-1) under Pt-free condition. The PHE activity has no obvious change after
      addition 1 wt.% Pt, implying the presence of active catalytic sites for hydrogen
      evolution in the PCMS-1. The easy synthesis process, low preparation cost of the
      PCMS makes their large potential for Pt-free PHE.

PMID- 25748689
TI  - Extramedullary plasmacytoma of the cricoid cartilage with solitary plasmacytoma
      of the rib.
AB  - BACKGROUND: Extramedullary plasmacytoma is a rare plasma cell neoplasm of the
      soft tissues characterized by the presence of a single, discrete lesion without
      evidence of systemic disease. Extramedullary plasmacytoma may disseminate into
      multiple myeloma, a systemic plasma cell disease. METHODS: A rare case of
      extramedullary plasmacytoma of the cricoid cartilage with solitary plasmacytoma
      of the rib was reviewed. RESULTS: The patient was found to have two discrete
      lesions; one of the cricoid cartilage and one of the lateral left fifth rib.
      Despite the presence of multiple tumors, the patient was not diagnosed with
      multiple myeloma as the bone marrow appeared normal. CONCLUSIONS: Due to the
      rarity of these neoplasms and the unusual localization of the extramedullary
      plasmacytoma tumor, a definitive diagnosis was difficult to make in this case.
      This case may be instructive for the differential diagnosis of laryngeal lesions.

PMID- 25748690
TI  - Minimally invasive surgery for pyriform sinus fistula by transoral
      videolaryngoscopic surgery.
AB  - Pyriform sinus fistula is a rare branchial anomaly that manifests as recurrent
      cervical infection resulting from contamination of the fistula internal orifice
      in the pyriform sinus. Although open neck surgery to resect the fistula has been
      recommended as a definitive treatment, identifying the fistula within the scar is
      difficult and occasionally results in recurrence. Here, we describe a novel
      transoral surgical technique for pyriform sinus fistula using transoral
      videolaryngoscopic surgery (TOVS) as a definitive treatment to resect and close
      the fistula without skin incision. Needle cautery enables fine excision and
      delicate dissection of the fistula tract. TOVS is a safe, easy, and reliable
      treatment and is a suitable first line treatment. 

PMID- 25748691
TI  - An item response theory analysis of the Executive Interview and development of
      the EXIT8: A Project FRONTIER Study.
AB  - INTRODUCTION: The Executive Interview (EXIT25) is an effective measure of
      executive dysfunction, but may be inefficient due to the time it takes to
      complete 25 interview-based items. The current study aimed to examine
      psychometric properties of the EXIT25, with a specific focus on determining
      whether a briefer version of the measure could comprehensively assess executive
      dysfunction. METHOD: The current study applied a graded response model (a type of
      item response theory model for polytomous categorical data) to identify items
      that were most closely related to the underlying construct of executive
      functioning and best discriminated between varying levels of executive
      functioning. Participants were 660 adults ages 40 to 96 years living in West
      Texas, who were recruited through an ongoing epidemiological study of rural
      health and aging, called Project FRONTIER. The EXIT25 was the primary measure
      examined. Participants also completed the Trail Making Test and Controlled Oral
      Word Association Test, among other measures, to examine the convergent validity
      of a brief form of the EXIT25. RESULTS: Eight items were identified that provided
      the majority of the information about the underlying construct of executive
      functioning; total scores on these items were associated with total scores on
      other measures of executive functioning and were able to differentiate between
      cognitively healthy, mildly cognitively impaired, and demented participants. In
      addition, cutoff scores were recommended based on sensitivity and specificity of
      scores. CONCLUSION: A brief, eight-item version of the EXIT25 may be an effective
      and efficient screening for executive dysfunction among older adults.

PMID- 25748692
TI  - Encapsulation method for atom probe tomography analysis of nanoparticles.
AB  - Open-space nanomaterials are a widespread class of technologically important
      materials that are generally incompatible with analysis by atom probe tomography
      (APT) due to issues with specimen preparation, field evaporation and data
      reconstruction. The feasibility of encapsulating such non-compact matter in a
      matrix to enable APT measurements is investigated using nanoparticles as an
      example. Simulations of field evaporation of a void, and the resulting artifacts
      in ion trajectory, underpin the requirement that no voids remain after
      encapsulation. The approach is demonstrated by encapsulating Pt nanoparticles in
      an ZnO:Al matrix created by atomic layer deposition, a growth technique which
      offers very high surface coverage and conformality. APT measurements of the Pt
      nanoparticles are correlated with transmission electron microscopy images and
      numerical simulations in order to evaluate the accuracy of the APT
      reconstruction. 

PMID- 25748693
TI  - Practice Variations between Emergency Physicians and Pediatricians in Treating
      Acute Bronchiolitis in the Emergency Department: A Nationwide Study.
AB  - BACKGROUND: Although supportive care is the mainstay management for acute
      bronchiolitis, non-evidence-based diagnostic testing and medications remain
      common in emergency departments (EDs). OBJECTIVE: Our aim was to compare
      emergency physicians (EPs) and pediatricians practice patterns in the management
      of acute bronchiolitis in the ED. METHODS: A cross-sectional study was conducted
      by using registration and claims datasets from 2008 to 2011. Patients with acute
      bronchiolitis were divided into EP group and pediatrician group. RESULTS: A total
      of 2174 patients were enrolled. The diagnostic tests used, including chest x-ray
      (63.7% vs. 46%; adjusted odds ratio [OR] = 2.27; 95% CI 1.77-2.91), complete
      blood count (33.2% vs. 21.8%; adjusted OR = 1.74; 95% CI 1.33-2.26), C-reactive
      protein (35.1% vs. 22.6%; adjusted OR = 1.79; 95% CI 1.38-2.33), blood culture
      (23.9% vs. 14.3%; adjusted OR = 1.79; 95% CI 1.33-2.39), and arterial blood gas
      (3.7% vs. 1.8%, adjusted OR = 2.38; 95% CI 1.21-4.67), were higher in the EP
      group than in the pediatrician group. Intravenous fluid administration was also
      higher in the EP group (20.8% vs. 3.5%; adjusted OR = 7.49; 95% CI 5.12-10.8). In
      addition, EPs more frequently arranged for hospital admissions (36% vs. 19.5%;
      adjusted OR = 2.51; 95% CI 1.15-3.26). CONCLUSIONS: Both EPs and pediatricians
      had high rates of ordering diagnostic testing for acute bronchiolitis patients in
      ED. Compared with pediatricians, EPs used more diagnostic tests for the patients
      with acute bronchiolitis in ED.

PMID- 25748694
TI  - Glissonian approach during hepathectomy (with video).

PMID- 25748695
TI  - Laparoscopic cholecystectomy and choledocolithotomy with primary suture for
      lithiasis (with video).

PMID- 25748696
TI  - Anterograde cholecystectomy by laparotomy for acute cholecystitis.

PMID- 25748697
TI  - Caudate lobe resection: The laparoscopic approach (with video).

PMID- 25748698
TI  - Renal effects of added low-dose dopamine in acute heart failure patients with
      diuretic resistance to natriuretic peptide.
AB  - Worsening renal function during the early phase of hospitalization is related to
      adverse outcomes in acute heart failure (AHF). This study aimed to clarify
      whether added low-dose dopamine (DA) is clinically beneficial for AHF patients
      with diuretic resistance to human atrial natriuretic peptide (hANP). Twenty-four
      AHF patients, who did not have adequate diuresis by 4 hours after administration
      of hANP, were randomized to a low dose of DA (1-3 MUg.kg.min, n = 12) or a low
      dose of furosemide (10-30 mg injection, n = 12). The significant increase in mean
      hourly urine volume from baseline (265% +/- 204% with hANP + DA; 187% +/- 118%
      with hANP + furosemide) and improvement of dyspnea were similarly observed in
      both groups. Significant decreases in serum creatinine levels were observed by 
      14.0% +/- 14.2% in the hANP + DA group compared with the hANP + furosemide group
      (4.5% +/- 9.6%, P = 0.0011) without increases in the renotubular and myocardial
      markers. The incidence of worsening renal function defined as a rise in serum
      creatinine of >0.3 mg/dL was not observed within 3 days of admission in both
      groups. Added low-dose DA might not have a harmful effect on renal function and
      effects of diuresis and symptom relief without a significant increase in troponin
      T in AHF patients with diuretic resistance to hANP.

PMID- 25748699
TI  - Activation of I(K1) channel by zacopride attenuates left ventricular remodeling
      in rats with myocardial infarction: Retraction.

PMID- 25748700
TI  - Iterative most-likely point registration (IMLP): a robust algorithm for computing
      optimal shape alignment.
AB  - We present a probabilistic registration algorithm that robustly solves the
      problem of rigid-body alignment between two shapes with high accuracy, by aptly
      modeling measurement noise in each shape, whether isotropic or anisotropic. For
      point-cloud shapes, the probabilistic framework additionally enables modeling
      locally-linear surface regions in the vicinity of each point to further improve
      registration accuracy. The proposed Iterative Most-Likely Point (IMLP) algorithm
      is formed as a variant of the popular Iterative Closest Point (ICP) algorithm,
      which iterates between point-correspondence and point-registration steps. IMLP's
      probabilistic framework is used to incorporate a generalized noise model into
      both the correspondence and the registration phases of the algorithm, hence its
      name as a most-likely point method rather than a closest-point method. To
      efficiently compute the most-likely correspondences, we devise a novel search
      strategy based on a principal direction (PD)-tree search. We also propose a new
      approach to solve the generalized total-least-squares (GTLS) sub-problem of the
      registration phase, wherein the point correspondences are registered under a
      generalized noise model. Our GTLS approach has improved accuracy, efficiency, and
      stability compared to prior methods presented for this problem and offers a
      straightforward implementation using standard least squares. We evaluate the
      performance of IMLP relative to a large number of prior algorithms including ICP,
      a robust variant on ICP, Generalized ICP (GICP), and Coherent Point Drift (CPD),
      as well as drawing close comparison with the prior anisotropic registration
      methods of GTLS-ICP and A-ICP. The performance of IMLP is shown to be superior
      with respect to these algorithms over a wide range of noise conditions, outliers,
      and misalignments using both mesh and point-cloud representations of various
      shapes. 

PMID- 25748701
TI  - Analysis of Environmental Chemical Mixtures and Non-Hodgkin Lymphoma Risk in the
      NCI-SEER NHL Study.
AB  - BACKGROUND: There are several suspected environmental risk factors for non
      Hodgkin lymphoma (NHL). The associations between NHL and environmental chemical
      exposures have typically been evaluated for individual chemicals (i.e., one-by
      one). OBJECTIVES: We determined the association between a mixture of 27
      correlated chemicals measured in house dust and NHL risk. METHODS: We conducted a
      population-based case-control study of NHL in four National Cancer Institute
      Surveillance, Epidemiology, and End Results centers--Detroit, Michigan; Iowa; Los
      Angeles County, California; and Seattle, Washington--from 1998 to 2000. We used
      weighted quantile sum (WQS) regression to model the association of a mixture of
      chemicals and risk of NHL. The WQS index was a sum of weighted quartiles for 5
      polychlorinated biphenyls (PCBs), 7 polycyclic aromatic hydrocarbons (PAHs), and
      15 pesticides. We estimated chemical mixture weights and effects for study sites
      combined and for each site individually, and also for histologic subtypes of NHL.
      RESULTS: The WQS index was statistically significantly associated with NHL
      overall [odds ratio (OR) = 1.30; 95% CI: 1.08, 1.56; p = 0.006; for one quartile
      increase] and in the study sites of Detroit (OR = 1.71; 95% CI: 1.02, 2.92; p =
      0.045), Los Angeles (OR = 1.44; 95% CI: 1.00, 2.08; p = 0.049), and Iowa (OR =
      1.76; 95% CI: 1.23, 2.53; p = 0.002). The index was marginally statistically
      significant in Seattle (OR = 1.39; 95% CI: 0.97, 1.99; p = 0.071). The most
      highly weighted chemicals for predicting risk overall were PCB congener 180 and
      propoxur. Highly weighted chemicals varied by study site; PCBs were more highly
      weighted in Detroit, and pesticides were more highly weighted in Iowa.
      CONCLUSIONS: An index of chemical mixtures was significantly associated with NHL.
      Our results show the importance of evaluating chemical mixtures when studying
      cancer risk.

PMID- 25748702
TI  - Association between neovascular age-related macular degeneration and dementia: a
      population-based case-control study in Taiwan.
AB  - BACKGROUND: Most available studies focusing on the association between
      neovascular age-related macular degeneration (AMD) and dementia have conflicting
      results. This study aimed to investigate the association between previously
      diagnosed AMD and dementia using a population-based dataset in Taiwan. METHODS:
      Data for this case-control study were retrospectively collected from the Taiwan
      National Health Insurance Research Database. We identified 13,402 subjects who
      had a diagnosis of dementia as cases, and 40,206 subjects without dementia as
      controls. A conditional logistic regression was used to examine the association
      of dementia with previously diagnosed neovascular AMD. RESULTS: We found that of
      the study sample of 53,608 subjects, 1.01% had previously diagnosed neovascular
      AMD, 1.35% and 0.90% for cases and the controls, respectively (p<0.001). The
      conditional logistic regression analysis suggested that the odds ratio of prior
      neovascular AMD for cases was 1.37 (95% confidence interval: 1.14~1.65) compared
      to the controls after adjusting for subjects' age, monthly income, geographic
      location, urbanization level, and hyperlipidemia, diabetes, hypertension, stroke,
      ischemic heart disease, and whether or not a subjects underwent cataract surgery
      prior to index date than controls. CONCLUSIONS: Dementia subjects were associated
      with a higher proportion of prior neovascular AMD than were the controls.

PMID- 25748703
TI  - Serine proteases of parasitic helminths.
AB  - Serine proteases form one of the most important families of enzymes and perform
      significant functions in a broad range of biological processes, such as intra-
      and extracellular protein metabolism, digestion, blood coagulation, regulation of
      development, and fertilization. A number of serine proteases have been identified
      in parasitic helminths that have putative roles in parasite development and
      nutrition, host tissues and cell invasion, anticoagulation, and immune evasion.
      In this review, we described the serine proteases that have been identified in
      parasitic helminths, including nematodes (Trichinella spiralis, T.
      pseudospiralis, Trichuris muris, Anisakis simplex, Ascaris suum, Onchocerca
      volvulus, O. lienalis, Brugia malayi, Ancylostoma caninum, and Steinernema
      carpocapsae), cestodes (Spirometra mansoni, Echinococcus granulosus, and
      Schistocephalus solidus), and trematodes (Fasciola hepatica, F. gigantica, and
      Schistosoma mansoni). Moreover, the possible biological functions of these serine
      proteases in the endogenous biological phenomena of these parasites and in the
      host-parasite interaction were also discussed. 

PMID- 25748704
TI  - Subtype distribution of Blastocystis in Thai-Myanmar border, Thailand.
AB  - Blastocystis sp. is a common zoonotic intestinal protozoa which has been
      classified into 17 subtypes (STs). A cross-sectional study was conducted to
      determine the prevalence and subtype distribution of Blastocystis in villagers
      living on the Thai-Myanmar border, where the risk of parasitic infection is high.
      A total of 207 stool samples were collected and DNA was extracted. PCR and
      sequencing using primers targeting small-subunit ribosomal RNA (SSU rRNA) gene
      were performed. The prevalence of Blastocystis infection was 37.2% (77/207). ST3
      (19.8%; 41/207) was the predominant subtype, followed by ST1 (11.6%; 24/207), ST2
      (5.3%; 11/207), and ST4 (0.5%; 1/207). A phylogenetic tree was reconstructed
      using the maximum likelihood (ML) method based on the Hasegawa-Kishino-Yano + G +
      I model. The percentage of bootstrapped trees in which the associated taxa
      clustered together was relatively high. Some sequences of Blastocystis positive
      samples (TK18, 39, 46, 71, and 90) were closely related to animals (pig and
      cattle) indicating zoonotic risks. Therefore, proper health education in
      parasitic prevention for the villagers should be promoted to improve their
      personal hygiene. Further longitudinal studies are required to monitor the
      prevalence of parasitic infections after providing health education and to
      investigate Blastocystis ST in animals living in these villages. 

PMID- 25748705
TI  - Antileishmanial and cytotoxic effects of essential oil and methanolic extract of
      Myrtus communis L.
AB  - Plants used for traditional medicine contain a wide range of substances that can
      be used to treat various diseases such as infectious diseases. The present study
      was designed to evaluate the antileishmanial effects of the essential oil and
      methanolic extract of Myrtus communis against Leishmania tropica on an in vitro
      model. Antileishmanial effects of essential oil and methanolic extract of M.
      communis on promastigote forms and their cytotoxic activities against J774 cells
      were evaluated using MTT assay for 72 hr. In addition, their leishmanicidal
      activity against amastigote forms was determined in a macrophage model, for 72
      hr. Findings showed that the main components of essential oil were alpha-pinene
      (24.7%), 1,8-cineole (19.6%), and linalool (12.6%). Findings demonstrated that M.
      communis, particularly its essential oil, significantly (P<0.05) inhibited the
      growth rate of promastigote and amastigote forms of L. tropica based on a dose
      dependent response. The IC50 values for essential oil and methanolic extract was
      8.4 and 28.9 MUg/ml against promastigotes, respectively. These values were 11.6
      and 40.8 MUg/ml against amastigote forms, respectively. Glucantime as control
      drug also revealed IC50 values of 88.3 and 44.6 MUg/ml for promastigotes and
      amastigotes of L. tropica, respectively. The in vitro assay demonstrated no
      significant cytotoxicity in J774 cells. However, essential oil indicated a more
      cytotoxic effect as compared with the methanolic extract of M. communis. The
      findings of the present study demonstrated that M. communis might be a natural
      source for production of a new leishmanicidal agent. 

PMID- 25748706
TI  - Seropositivity and serointensity of Toxoplasma gondii antibodies and DNA among
      patients with schizophrenia.
AB  - The aim of this cross sectional case control study was to examine the
      serofrequency and serointensity of Toxoplasma gondii (Tg) IgG, IgM, and DNA among
      patients with schizophrenia. A total of 101 patients with schizophrenia and 55
      healthy controls from Sungai Buloh Hospital, Selangor, Malaysia and University
      Malaya Medical Center (UMMC) were included in this study. The diagnosis of
      schizophrenia was made based on the Diagnostic and Statistical Manual of Mental
      Disorders, Fourth Edition (DSM-IV). The presence of Tg infection was examined
      using both indirect (ELISA) and direct (quantitative real-time PCR) detection
      methods by measuring Tg IgG and IgM and DNA, respectively. The serofrequency of
      Tg IgG antibodies (51.5%, 52/101) and DNA (32.67%, 33/101) among patients with
      schizophrenia was significantly higher than IgG (18.2%, 10/55) and DNA (3.64%,
      2/55) of the controls (IgG, P=0.000, OD=4.8, CI=2.2-10.5; DNA, P=0.000, OD=12.9,
      CI=2.17-10.51). However, the Tg IgM antibody between patients with schizophrenia
      and controls was not significant (P>0.005). There was no significant difference
      (P>0.005) in both serointensity of Tg IgG and DNA between patients with
      schizophrenia and controls. These findings have further demonstrated the strong
      association between the active Tg infection and schizophrenia. 

PMID- 25748707
TI  - Sensitivity of Plasmodium falciparum to antimalarial drugs in Hainan Island,
      China.
AB  - Pyronaridine and artesunate have been shown to be effective in falciparum malaria
      treatment. However, pyronaridine is rarely used in Hainan Island clinically, and
      artesunate is not widely used as a therapeutic agent. Instead, conventional
      antimalarial drugs, chloroquine and piperaquine, are used, explaining the
      emergence of chloroquine-resistant Plasmodium falciparum. In this article, we
      investigated the sensitivity of P. falciparum to antimalarial drugs used in
      Hainan Island for rational drug therapy. We performed in vivo (28 days) and in
      vitro tests to determine the sensitivity of P. falciparum to antimalarial drugs.
      Total 46 patients with falciparum malaria were treated with
      dihydroartemisinin/piperaquine phosphate (DUO-COTECXIN) and followed up for 28
      day. The cure rate was 97.8%. The mean fever clearance time (22.5 +/- 10.6 hr)
      and the mean parasite clearance time (27.3 +/- 12.2 hr) showed no statistical
      significance with different genders, ages, temperatures, or parasite density (P >
      0.05). The resistance rates of chloroquine, piperaquine, pyronarididine, and
      artesunate detected in vitro were 71.9%, 40.6%, 12.5%, and 0%, respectively (P <
      0.0001). The resistance intensities decreased as follows: chloroquine >
      piperaquine > pyronarididine > artesunate. The inhibitory dose 50 (IC50) was 3.77
      * 10(-6) mol/L, 2.09 * 10(-6) mol/L, 0.09 * 10(-6) mol/L, and 0.05 * 10(-6)
      mol/L, and the mean concentrations for complete inhibition (CIMC) of schizont
      formation were 5.60 * 10(-6) mol/L, 9.26 * 10(-6) mol/L, 0.55 * 10(-6) mol/L, and
      0.07 * 10(-6) mol/L, respectively. Dihydroartemisinin showed a strong therapeutic
      effect against falciparum malaria with a low toxicity.

PMID- 25748708
TI  - Plasmodium vivax drug resistance genes; Pvmdr1 and Pvcrt-o polymorphisms in
      relation to chloroquine sensitivity from a malaria endemic area of Thailand.
AB  - The aim of the study was to explore the possible molecular markers of chloroquine
      resistance in Plasmodium vivax isolates in Thailand. A total of 30 P. vivax
      isolates were collected from a malaria endemic area along the Thai-Myanmar border
      in Mae Sot district of Thailand. Dried blood spot samples were collected for
      analysis of Pvmdr1 and Pvcrt-o polymorphisms. Blood samples (100 MUl) were
      collected by finger-prick for in vitro chloroquine susceptibility testing by
      schizont maturation inhibition assay. Based on the cut-off IC50 of 100 nM, 19
      (63.3%) isolates were classified as chloroquine resistant P. vivax isolates.
      Seven non-synonymous mutations and 2 synonymous were identified in Pvmdr1 gene.
      Y976F and F1076L mutations were detected in 7 (23.3%) and 16 isolates (53.3%),
      respectively. Analysis of Pvcrt-o gene revealed that all isolates were wild-type.
      Our results suggest that chloroquine resistance gene is now spreading in this
      area. Monitoring of chloroquine resistant molecular markers provide a useful tool
      for future control of P. vivax malaria. 

PMID- 25748709
TI  - Immunopathological changes in the brain of immunosuppressed mice experimentally
      infected with Toxocara canis.
AB  - Toxocariasis is a soil-transmitted helminthozoonosis due to infection of humans
      by larvae of Toxocara canis. The disease could produce cognitive and behavioral
      disturbances especially in children. Meanwhile, in our modern era, the incidence
      of immunosuppression has been progressively increasing due to increased incidence
      of malignancy as well as increased use of immunosuppressive agents. The present
      study aimed at comparing some of the pathological and immunological alterations
      in the brain of normal and immunosuppressed mice experimentally infected with T.
      canis. Therefore, 180 Swiss albino mice were divided into 4 groups including
      normal (control) group, immunocompetent T. canis-infected group, immunosuppressed
      group (control), and immunosuppressed infected group. Infected mice were
      subjected to larval counts in the brain, and the brains from all mice were
      assessed for histopathological changes, astrogliosis, and IL-5 mRNA expression
      levels in brain tissues. The results showed that under immunosuppression, there
      were significant increase in brain larval counts, significant enhancement of
      reactive gliosis, and significant reduction in IL-5 mRNA expression. All these
      changes were maximal in the chronic stage of infection. In conclusion, the
      immunopathological alterations in the brains of infected animals were progressive
      over time, and were exaggerated under the effect of immunosuppression as did the
      intensity of cerebral infection. 

PMID- 25748710
TI  - Experimental life history and biological characteristics of Fasciola gigantica
      (Digenea: Fasciolidae).
AB  - This study was conducted to investigate the life history, morphology, and
      maturation of larval stages and adult worms of Fasciola gigantica in experimental
      mice. Lymnaea auricularia rubiginosa was used as the intermediate host, and Oryza
      sativa was used for encystment of the metacercariae, while Mus musculus was used
      as the definitive host for maturation study. Fresh eggs from the gall bladder of
      water buffaloes fully developed into embryonated ones and hatched out at days 11
      12 after incubation at about 29oC. Free-swimming miracidia rapidly penetrated
      into the snail host, and gradually developed into the next larval stages;
      sporocyst, redia, and daughter redia with cercariae. Fully-developed cercariae
      were separated from the redia and shed from the snails on day 39 post-infection
      (PI). Free-swimming cercariae were immediately allowed to adhere to rice plants,
      and capsules were constructed to protect metacercariae on rice plants. Juvenile
      worms were detected in intestines of mice at days 3 and 6 PI, but they were found
      in the bile duct from day 9 PI. Juvenile and adult flukes were recovered from 16
      mice experimentally infected with metacercariae, with the average recovery rate
      of 35.8%. Sexually mature adult flukes were recovered from day 42 PI. It could be
      confirmed that experimentally encysted metacercariae could infect and develop to
      maturity in the experimental host. The present study reports for the first time
      the complete life history of F. gigantica by an experimental study in Thailand.
      The obtained information can be used as a guide for prevention, elimination, and
      treatment of F. gigantica at environment and in other hosts. 

PMID- 25748711
TI  - Identification and molecular characterization of Parkin in Clonorchis sinensis.
AB  - Clonorchis sinensis habitating in the bile duct of mammals causes clonorchiasis
      endemic in East Asian countries. Parkin is a RING-between-RING protein and has E3
      ubiquitin ligase activity catalyzing ubiquitination and degradation of substrate
      proteins. A cDNA clone of C. sinensis was predicted to encode a polypeptide
      homologous to parkin (CsParkin) including 5 domains (Ubl, RING0, RING1, IBR, and
      RING2). The cysteine and histidine residues binding to Zn(2+) were all conserved
      and participated in formation of tertiary structural RINGs. Conserved residues
      were also an E2-binding site in RING1 domain and a catalytic cysteine residue in
      the RING2 domain. Native CsParkin was determined to have an estimated molecular
      weight of 45.7 kDa from C. sinensis adults by immunoblotting. CsParkin revealed
      E3-ubiquitin ligase activity and higher expression in metacercariae than in
      adults. CsParkin was localized in the locomotive and male reproductive organs of
      C. sinensis adults, and extensively in metacercariae. Parkin has been found to
      participate in regulating mitochondrial function and energy metabolism in
      mammalian cells. From these results, it is suggested that CsParkin play roles in
      energy metabolism of the locomotive organs, and possibly in protein metabolism of
      the reproductive organs of C. sinensis. 

PMID- 25748712
TI  - Xenomonitoring of different filarial nematodes using single and multiplex PCR in
      mosquitoes from Assiut Governorate, Egypt.
AB  - Wuchereria bancrofti, Dirofilaria immitis, and Dirofilaria repens are filarial
      nematodes transmitted by mosquitoes belonging to Culex, Aedes, and Anopheles
      genera. Screening by vector dissection is a tiresome technique. We aimed to
      screen filarial parasites in their vectors by single and multiplex PCR and
      evaluate the usefulness of multiplex PCR as a rapid xenomonitoring and
      simultaneous differentiation tool, in area where 3 filarial parasites are
      coexisting. Female mosquitoes were collected from 7 localities in Assiut
      Governorate, were microscopically identified and divided into pools according to
      their species and collection site. Detection of W. bancrofti, D. immitis, and D.
      repens using single PCR was reached followed by multiplex PCR. Usefulness of
      multiplex PCR was evaluated by testing mosquito pools to know which genera and
      species are used by filarial parasites as a vector. An overall estimated rate of
      infection (ERI) in mosquitoes was 0.6%; the highest was Culex spp. (0.47%). W.
      bancrofti, D. immitis, and D. repens could be simultaneously and differentially
      detected in infected vectors by using multiplex PCR. Out of 100 mosquito pools, 8
      were positive for W. bancrofti (ERI of 0.33%) and 3 pools each were positive for
      D. immitis and D. repens (ERI 0.12%). The technique showed 100% sensitivity and
      98% specificity. El-Nikhila, El-Matiaa villages, and Sahel Seleem district in
      Assiut Governorate, Egypt are still endemic foci for filarial parasites.
      Multiplex PCR offers a reliable procedure for molecular xenomonitoring of
      filariasis within their respective vectors in endemic areas. Therefore, it is
      recommended for evaluation of mosquito infection after lymphatic filariasis
      eradication programs. 

PMID- 25748713
TI  - Proteomic screening of antigenic proteins from the hard tick, Haemaphysalis
      longicornis (Acari: Ixodidae).
AB  - Proteomic tools allow large-scale, high-throughput analyses for the detection,
      identification, and functional investigation of proteome. For detection of
      antigens from Haemaphysalis longicornis, 1-dimensional electrophoresis (1-DE)
      quantitative immunoblotting technique combined with 2-dimensional electrophoresis
      (2-DE) immunoblotting was used for whole body proteins from unfed and partially
      fed female ticks. Reactivity bands and 2-DE immunoblotting were performed
      following 2-DE electrophoresis to identify protein spots. The proteome of the
      partially fed female had a larger number of lower molecular weight proteins than
      that of the unfed female tick. The total number of detected spots was 818 for
      unfed and 670 for partially fed female ticks. The 2-DE immunoblotting identified
      10 antigenic spots from unfed females and 8 antigenic spots from partially fed
      females. Matrix Assisted Laser Desorption Ionization-Time of Flight Mass
      Spectrometry (MALDI-TOF) of relevant spots identified calreticulin, putative
      secreted WC salivary protein, and a conserved hypothetical protein from the
      National Center for Biotechnology Information and Swiss Prot protein sequence
      databases. These findings indicate that most of the whole body components of
      these ticks are non-immunogenic. The data reported here will provide guidance in
      the identification of antigenic proteins to prevent infestation and diseases
      transmitted by H. longicornis. 

PMID- 25748715
TI  - First record of Cosmocephalus obvelatus (Acuariidae) in common gulls (Larus
      canus) from Gangneung, Korea.
AB  - A nematode species belonging to the genus Cosmocephalus was collected from the
      stomach of 2 common gulls, Larus canus. The common gulls were found dead on the
      seaside of Gangneung City, the Republic of Korea. The worms were identified and
      classified by light (LM) and scanning electron microscopy (SEM) on the basis of
      important taxonomic characters. The nematodes were characterized by a body length
      9.1-9.3 mm (males) and 15.5-15.9 mm (females) and cordons recurrent in anterior
      direction and anastomosing laterally at about the level of anterior quarter of
      the buccal cavity. The salient bicuspid deirids were located on the posterior to
      the cordons. Lateral alae were well-developed, extending from the level just
      posterior of deirids to the level about middle of the body. LM and SEM
      observations identified the worms as C. obvelatus. This is the first reported
      case of C. obvelatus infection in common gulls in Korea. 

PMID- 25748714
TI  - Comorbid gastric adenocarcinoma and gastric and duodenal Strongyloides
      stercoralis infection: a case report.
AB  - Strongyloides stercoralis can cause systemic infection, termed strongyloidiasis,
      and gastrointestinal ulcer disease in immunocompromised patients. However, to our
      knowledge, there are no reported cases of comorbid gastric adenocarcinoma and S.
      stercoralis infection. Here, we report a case of an 81-year-old Korean man who
      presented with S. stercoralis infection coexisting with early gastric
      adenocarcinoma (T1aN0M0). S. stercoralis eggs, rhabditiform larvae, and adult
      females were observed in normal gastric and duodenal crypts. They were also
      observed in atypical glands representative of adenocarcinoma and adenoma.
      Preliminary laboratory tests revealed mild neutrophilic and eosinophilic
      leukocytosis. A routine stool test failed to detect rhabditiform larvae in the
      patient's fecal sample; however, S. stercoralis was identified by PCR
      amplification and 18S rRNA sequencing using genomic DNA extracted from formalin
      fixed paraffin-embedded tissues. Postoperatively, the patient had a persistent
      fever and was treated with albendazole for 7 days, which alleviated the fever.
      The patient was followed-up by monitoring and laboratory testing for 4 months
      postoperatively, and no abnormalities were observed thus far. The fact that S.
      stercoralis infection may be fatal in immunocompromised patients should be kept
      in mind when assessing high-risk patients. 

PMID- 25748716
TI  - Four additional cases of Diphyllobothrium nihonkaiense infection confirmed by
      analysis of COX1 gene in Korea.
AB  - Most of the diphyllobothriid tapeworms isolated from human samples in the
      Republic of Korea (= Korea) have been identified as Diphyllobothrium nihonkaiense
      by genetic analysis. This paper reports confirmation of D. nihonkaiense
      infections in 4 additional human samples obtained between 1995 and 2014, which
      were analyzed at the Department of Parasitology, Hallym University College of
      Medicine, Korea. Analysis of the mitochondrial cytochrome c oxidase 1 (cox1) gene
      revealed a 98.5-99.5% similarity with a reference D. nihonkaiense sequence in
      GenBank. The present report adds 4 cases of D. nihonkaiense infections to the
      literature, indicating that the dominant diphyllobothriid tapeworm species in
      Korea is D. nihonkaiense but not D. latum. 

PMID- 25748717
TI  - Diphyllobothrium nihonkaiense infections in a family.
AB  - Diphyllobothrium latum and Diphyllobothrium nihonkaiense are morphologically
      similar to each other, and only genetic method can differentiate clearly between
      the 2 species. A strobila of diphyllobothriid tapeworm discharged from a 7-year
      old boy was analyzed to identify the species by mitochondrial cytochrome c
      oxidase subunit 1 (cox1) gene sequencing. He and his family (total 4 persons) ate
      slices of 3 kinds of raw fish 16 days before visiting our outpatient clinic. All
      family members complained of abdominal pain and watery diarrhea. They all
      expelled tapeworm strobilae in their stools. They were treated with a single oral
      dose of praziquantel and then complained of no more symptoms. The cox1 gene
      sequencing of the strobila from the boy revealed 99.9% (687/688 bp) similarity
      with D. nihonkaiense and only 93.2% (641/688 bp) similarity with D. latum. Thus,
      we assigned this tapeworm as D. nihonkaiense. This is the first report of D.
      nihonkaiense infection in a family in Korea, and this report includes the 8th
      pediatric case in Korea. The current report is meaningful because D. nihonkaiense
      infection within a family is rare. 

PMID- 25748718
TI  - Cryptosporidium suis infection in post-weaned and adult pigs in Shaanxi province,
      northwestern China.
AB  - Cryptosporidium spp., ubiquitous enteric parasitic protozoa of vertebrates,
      recently emerged as an important cause of economic loss and zoonosis. The present
      study aimed to determine the distribution and species of Cryptosporidium in post
      weaned and adult pigs in Shaanxi province, northwestern China. A total of 1,337
      fresh fecal samples of post-weaned and adult pigs were collected by sterile
      disposable gloves from 8 areas of Shaanxi province. The samples were examined by
      Sheather's sugar flotation technique and microscopy at * 400 magnification for
      Cryptosporidium infection, and the species in positive samples was further
      identified by PCR amplification of the small subunit (SSU) rRNA gene. A total of
      44 fecal samples were successfully amplified by the nested PCR of the partial SSU
      rRNA, with overall prevalence of 3.3%. The average prevalence of Cryptosporidium
      infection in each pig farms ranged from 0 to 14.4%. Species identification by
      sequencing of SSU rRNA gene revealed that 42 (3.1%) samples were Cryptosporidium
      suis and 2 (0.15%) were Cryptosporidium scrofarum. C. suis had the highest
      prevalence (7.5%) in growers and the lowest in breeding pigs (0.97%). C. suis was
      the predominant species in pre-weaned and adult pigs, while C. scrofarum infected
      pigs older than 3 months only. A season-related difference of C. suis was
      observed in this study, with the highest prevalence in autumn (5.5%) and the
      lowest (1.7%) in winter. The present study provided basic information for control
      of Cryptosporidium infection in pigs and assessment of zoonotic transmission of
      pigs in Shaanxi province, China.

PMID- 25748719
TI  - Occurrence and molecular identification of Giardia duodenalis from stray cats in
      Guangzhou, southern China.
AB  - The objective of this study was to genetically characterize isolates of Giardia
      duodenalis and to determine if zoonotic potential of G. duodenalis could be found
      in stray cats from urban and suburban environments in Guangzhou, China. Among 102
      fresh fecal samples of stray cats, 30 samples were collected in Baiyun district
      (urban) and 72 in Conghua district (suburban). G. duodenalis specimens were
      examined using light microscopy, then the positive specimens were subjected to
      PCR amplification and subsequent sequencing at 4 loci such as glutamate
      dehydrogenase (gdh), triose phosphate isomerase (tpi), beta-giardin (bg), and
      small subunit ribosomal RNA (18S rRNA) genes. The phylogenetic trees were
      constructed using obtained sequences by MEGA5.2 software. Results show that 9.8%
      (10/102) feline fecal samples were found to be positive by microscopy, 10% (3/30)
      in Baiyun district and 9.7% (7/72) in Conghua district. Among the 10 positive
      samples, 9 were single infection (8 isolates, assemblage A; 1 isolate, assemblage
      F) and 1 sample was mixed infection with assemblages A and C. Based on tpi, gdh,
      and bg genes, all sequences of assemblage A showed complete homology with AI
      except for 1 isolate (CHC83). These findings not only confirmed the occurrence of
      G. duodenalis in stray cats, but also showed that zoonotic assemblage A was found
      for the first time in stray cats living in urban and suburban environments in
      China. 

PMID- 25748720
TI  - Prevalence and genetic characterization of Toxoplasma gondii in pet dogs in
      Central China.
AB  - The prevalence and genotype of Toxoplasma gondii infection in dogs in Henan
      Province, Central China was investigated. A total of 125 blood samples were
      collected from pet dogs during April to June 2013, and all samples were examined
      by indirect hemagglutination antibody test (IHA) and nested PCR. The overall T.
      gondii prevalence in pet dogs was 24.0% (30/125), with 20.8% (26/125) in IHA and
      10.4% (13/125) in PCR, respectively. No statistical associations were found
      between animal gender and age and the prevalence of T. gondii infection. Thirteen
      positive DNA samples were genotyped using 11 PCR-RFLP markers, including SAG1,
      (3'+5') SAG2, alt.SAG2, SAG3, BTUB, GRA6, c22-8, c29-2, L358, PK1, and Apico. Of
      these, only 2 samples were genotyped with complete data for all loci, and a novel
      genotype (type III at SAG3 and GRA6 loci, and type I at other loci) was
      identified. This is the first report of genetic characterization of T. gondii
      infection in dogs in China. 

PMID- 25748721
TI  - High genetic variability of Schistosoma haematobium in Mali and Nigeria.
AB  - Schistosoma haematobium is one of the most prevalent parasitic flatworms,
      infecting over 112 million people in Africa. However, little is known about the
      genetic diversity of natural S. haematobium populations from the human host
      because of the inaccessible location of adult worms in the host. We used 4
      microsatellite loci to genotype individually pooled S. haematobium eggs directly
      from each patient sampled at 4 endemic locations in Africa. We found that the
      average allele number of individuals from Mali was significantly higher than that
      from Nigeria. In addition, no significant difference in allelic composition was
      detected among the populations within Nigeria; however, the allelic composition
      was significantly different between Mali and Nigeria populations. This study
      demonstrated a high level of genetic variability of S. haematobium in the
      populations from Mali and Nigeria, the 2 major African endemic countries,
      suggesting that geographical population differentiation may occur in the regions.

PMID- 25748722
TI  - Intestinal nematodes from small mammals captured near the demilitarized zone,
      Gyeonggi province, Republic of Korea.
AB  - A total of 1,708 small mammals (1,617 rodents and 91 soricomorphs), including
      Apodemus agrarius (n = 1,400), Microtus fortis (167), Crocidura lasiura (91), Mus
      musculus (32), Myodes (= Eothenomys) regulus (9), Micromys minutus (6), and
      Tscherskia (= Cricetulus) triton (3), were live-trapped at US/Republic of Korea
      (ROK) military training sites near the demilitarized zone (DMZ) of Paju, Pocheon,
      and Yeoncheon, Gyeonggi Province from December 2004 to December 2009. Small
      mammals were examined for their intestinal nematodes by necropsy. A total of
      1,617 rodents (100%) and 91 (100%) soricomorphs were infected with at least 1
      nematode species, including Nippostrongylus brasiliensis, Heligmosomoides
      polygyrus, Syphacia obvelata, Heterakis spumosa, Protospirura muris, Capillaria
      spp., Trichuris muris, Rictularia affinis, and an unidentified species. N.
      brasiliensis was the most common species infecting small mammals (1,060; 62.1%)
      followed by H. polygyrus (617; 36.1%), S. obvelata (370; 21.7%), H. spumosa (314;
      18.4%), P. muris (123; 7.2%), and Capillaria spp. (59; 3.5%). Low infection rates
      (0.1-0.8%) were observed for T. muris, R. affinis, and an unidentified species.
      The number of recovered worms was highest for N. brasiliensis (21,623 worms; mean
      20.4 worms/infected specimen) followed by S. obvelata (9,235; 25.0 worms), H.
      polygyrus (4,122; 6.7 worms), and H. spumosa (1,160; 3.7 worms). A. agrarius
      demonstrated the highest prevalence for N. brasiliensis (70.9%), followed by M.
      minutus (50.0%), T. triton (33.3%), M. fortis (28.1%), M. musculus (15.6%), C.
      lasiura (13.2%), and M. regulus (0%). This is the first report of nematode
      infections in small mammals captured near the DMZ in ROK. 

PMID- 25748723
TI  - Bioaccessibility and digestive stability of carotenoids in cooked eggs studied
      using a dynamic in vitro gastrointestinal model.
AB  - Among dietary carotenoids, lutein and zeaxanthin are known to protect against age
      related macular degeneration, a leading cause of irreversible vision loss in the
      elderly. Egg yolk is rich in lutein and zeaxanthin, however, the effect of
      cooking and gastrointestinal digestion on yolk carotenoids is poorly understood.
      An in vitro dynamic gastrointestinal model (TIM-1) was used to investigate the
      digestive stability and bioaccessibility of carotenoids from boiled, fried, and
      scrambled eggs. Bioaccessibility but not digestive stability was significantly
      affected by the method of cooking. The main egg carotenoids, all-E-lutein and all
      E-zeaxanthin, were stable during the digestion with average recoveries of 90 and
      88%, respectively. No trans-cis isomerization of carotenoids was observed during
      digestion. Both all-E-lutein and all-E-zeaxanthin from scrambled eggs showed
      significantly lower bioaccessibility compared to boiled eggs. The results
      indicate that the bioaccessibility of egg carotenoids can be affected by
      different food preparation methods. 

PMID- 25748724
TI  - Multiple inorganic toxic substances contaminating the groundwater of Myingyan
      Township, Myanmar: arsenic, manganese, fluoride, iron, and uranium.
AB  - In South Asia, the technological and societal shift from drinking surface water
      to groundwater has resulted in a great reduction of acute diseases due to water
      borne pathogens. However, arsenic and other naturally occurring inorganic toxic
      substances present in groundwater in the region have been linked to a variety of
      chronic diseases, including cancers, heart disease, and neurological problems.
      Due to the highly specific symptoms of chronic arsenic poisoning, arsenic was the
      first inorganic toxic substance to be noticed at unsafe levels in the groundwater
      of West Bengal, India and Bangladesh. Subsequently, other inorganic toxic
      substances, including manganese, uranium, and fluoride have been found at unsafe
      levels in groundwater in South Asia. While numerous drinking water wells
      throughout Myanmar have been tested for arsenic, relatively little is known about
      the concentrations of other inorganic toxic substances in Myanmar groundwater. In
      this study, we analyzed samples from 18 drinking water wells (12 in Myingyan City
      and 6 in nearby Tha Pyay Thar Village) and 2 locations in the Ayeyarwaddy River
      for arsenic, boron, barium, beryllium, cadmium, cobalt, chromium, copper,
      fluoride, iron, mercury, manganese, molybdenum, nickel, lead, antimony, selenium,
      thallium, uranium, vanadium, and zinc. Concentrations of arsenic, manganese,
      fluoride, iron, or uranium exceeded health-based reference values in most wells.
      In addition, any given well usually contained more than one toxic substance at
      unsafe concentrations. While water testing and well sharing could reduce health
      risks, none of the wells sampled provide water that is entirely safe with respect
      to inorganic toxic substances. It is imperative that users of these wells, and
      users of other wells that have not been tested for multiple inorganic toxic
      substances throughout the region, be informed of the need for drinking water
      testing and the health consequences of drinking water contaminated with inorganic
      toxic substances. 

PMID- 25748725
TI  - Developing a "highway code" to steer the structural and electronic properties of
      Fe(III)/Dy(III) coordination clusters.
AB  - In the recently established field of 3d/4f coordination cluster (CC) chemistry
      several burning questions still need to be addressed. It is clear that combining
      3d and 4f metal ions within a coordination cluster core has the potential to lead
      to electronic structures that will be very difficult to describe but can also be
      extremely interesting. Furthermore, understanding why certain core topologies
      seem to be favored is difficult to predict. Here we show that the secondary
      coordination sphere provided by the ligands influences the favored product, as
      demonstrated for the compound [Fe4Dy2(MU3-OH)2(n-bdea)4(C6H5CO2)8].MeCN (1),
      which has a 2Fe:2Dy:2Fe core and was made using [Fe(III)3O(C6H5)CO2)(L)3](+) as
      starting material plus Dy(NO3)3 and N-n-butyl-diethanolamine (n-bdeaH2), compared
      with the compound made using a methyl meta-substituent (R) on the phenyl ring of
      the benzoate, [Fe(III)3O(C6H4Me)CO2)(L)3](+) as starting material, which resulted
      in the "square-in-square" compound [Fe4Dy4(MU3-OH)4(n-bdea)4(O2CC6H4CH3)12].MeCN
      (2) when using ambient conditions. Changing reaction conditions from ambient to
      solvothermal leads to "double-propeller" compounds [Fe4Dy4(MU4-O)3(n
      bdea)3(C6H5CO2)12].13MeCN (3) and [Fe4Dy4(MU4-O)3(n-bdea)3(O2CC6H4CH3)12].MeCN
      (4) forming with this core, resulting irrespective of the substitution on the
      iron benzoate starting material. Furthermore, compounds 1 and 2 can be
      transformed into compounds 3 and 4, respectively, using a solvothermal method.
      Thus, compounds 3 and 4 appear to be the thermodynamically most stable species.
      The factors steering the reactions toward these products are discussed. The
      electronic structures have been investigated using magnetic and Mossbauer
      studies. All compounds are cooperatively coupled 3d/4f systems, with compound 1
      showing single-molecule magnet behavior. 

PMID- 25748726
TI  - BK Virus-Associated Nephropathy with Plasma Cell-Rich Infiltrates Treated by
      Bortezomib-Based Regimen.
AB  - BK virus infection accompanied with plasma cell-rich infiltrates is a dilemma in
      renal transplant recipients. One young female patient diagnosed as BK virus
      associated nephropathy with plasma cell-rich infiltrates at 16 months after renal
      transplant was treated with bortezomib and a sequential immuno-suppressive
      protocol of tacrolimus combined with leflunomide. After a short period of
      reduction, her serum creatinine increased slowly with stable BK viruria. The
      patient underwent repeat biopsy. The histologic changes showed a decrease in
      plasma cells and CD20+ cells in the allograft, but the other mononuclear cells
      showed no difference from the first biopsy. The immunosuppressive protocol was
      converted to tacrolimus combined with enteric-coated mycophenolate sodium. Her
      serum creatinine decreased gradually during 6 months of follow-up. We speculate
      that bortezomib can be used in BK virus-associated nephropathy accompanied with
      plasma cell-rich infiltrates, and this effect might be mediated through a
      decrease of plasma cells and CD20+ cells in the allograft. The dosage and time of
      therapy need to be explored in the future; additional studies of large samples
      are needed.

PMID- 25748727
TI  - Cacna1f gene decreased contractility of skeletal muscle in rat model with
      congenital stationary night blindness.
AB  - The CACNA1F gene encodes a member of the alpha-1F subunit family in the voltage
      dependent calcium channel (Cav1.4) complex. Mutations in this gene result in
      incomplete congenital stationary night blindness (iCSNB2) in humans. And Cav1.4
      mutation could affect the functions of the skeletal muscle. This study
      investigated the role of Cacna1f mutations in alteration of the skeletal muscle
      functions in a Cacna1f mutation rat model (Cacna1f(CSNB2) rat). We found that the
      muscle endurance behaviors of Cacna1f(CSNB2) rats were significantly lower than
      those of the wild-type rats. The high-frequency fatigue resistance of the soleus
      muscle was decreased in Cacna1f(CSNB2) rats under continuous tetanic stimulation.
      The expression levels of the syntaxin (SYN) proteins in the soleus of the
      Cacna1f(CSNB2) rats were lower than those of wild-type rats. SYN was expressed in
      the soleus muscle, but not in the extensor digitorum longus. The Cav1.4 protein
      was not detected in the skeletal muscle of Cacna1f(CSNB2) rats. The Cacna1f mRNA
      level in the soleus of Cacna1f(CSNB2) rats was decreased compared with that in
      wild-type rats. This study demonstrated for the first time that the Cacna1f
      mutation reduces the function of slow-twitch skeletal muscle. And it also
      demonstrated that the Cacna1f gene affects synapse-associated protein expression,
      which may block the signal transmission in synaptic connectivity of the retina
      and skeletal muscle in Cacna1f-mutant rats.

PMID- 25748728
TI  - Increased expression of MMP14 correlates with the poor prognosis of Chinese
      patients with gastric cancer.
AB  - The role of matrix metalloproteinase 14 (MMP14) has been identified to involve
      tumor progression and prognosis. The purpose of this study is to investigate the
      role of MMP14 in tumor progression and prognosis of gastric cancer. This study
      indicated that MMP14 mRNA and protein were overexpressed in gastric cancer tissue
      (P<0.001 and P=0.037, respectively) and significantly associated with clinical
      stage (P=0.005), lymph node metastasis (P=0.003), and distant metastasis
      (P=0.017). Moreover, we found that the overexpression of MMP14 was a significant
      predictor of poor prognosis for gastric cancer patients (P<0.001). Furthermore,
      we performed a meta-analysis which included 594 cases from 3 studies and showed
      that MMP14 overexpression was a significantly poor prognostic factor in Chinese
      patients with gastric cancer and HR (95% CI) was 2.17 (1.64-2.86). In conclusion,
      MMP14 plays an important role on gastric cancer progression and prognosis and
      acts as a convictive biomarker for prognostic prediction for Chinese patients
      with gastric cancer.

PMID- 25748729
TI  - Compound heterozygous protein C deficiency in a family with venous thrombosis:
      Identification and in vitro study of p.Asp297His and p.Val420Leu mutations.
AB  - Hereditary protein C deficiency (PCD) is an autosomal inherited disorder
      associated with high risk for venous thromboembolism (VTE). This study aimed to
      explore the functional consequences of two missense mutations, p.Asp297His and
      p.Val420Ile, responsible for type I/II PCD and recurrent deep vein thrombosis
      (DVT) in a Chinese family. The plasma protein C activities (PC:A) of the proband
      and his sister were reduced to 4% and 5% of normal activity. However, protein C
      antigen (PC:Ag) concentrations were not equally decreased, with levels of 90.5%
      and 88.7%, respectively. Two missense mutations p.Asp297His and p.Val420Leu were
      identified in the protein C gene (PROC). The PC:A and PC:Ag levels in
      heterozygous state for p.Asp297His were 66% and 64.8%, whereas in heterozygous
      state for p.Val420Leu, these levels were 67% and 145%, respectively. Wild type
      (WT) and two mutant PROC cDNA expression plasmids were constructed and
      transfected into HEK 293T cells. Western blot analysis revealed that both
      p.Asp297His and p.Val420Leu showed a normal intracellular protein level. The
      extracellular protein level and specific activity of p.Asp297His were equally
      reduced to 37.7 +/- 4.3% and 22.1 +/- 2.5%, respectively. Mutant p.Val420Leu
      showed a relatively higher PC:Ag level and undetectable PC:A. Immunofluorescence
      staining revealed that WT and p.Val420Leu proteins were largely co-localized with
      both the protein disulfide isomerase (PDI) and cis-Golgi Marker (GM130), while
      the PC p.Asp297His mutant protein was mainly co-localized with PDI and much less
      co-localized with GM130. The thrombosis symptom in this family was associated
      with the two missense mutations in the PROC gene.

PMID- 25748730
TI  - Paeoniflorin diminishes ConA-induced IL-8 production in primary human hepatic
      sinusoidal endothelial cells in the involvement of ERK1/2 and Akt
      phosphorylation.
AB  - Liver diseases are closely associated with elevated levels of interleukin-8 (IL
      8), suggesting the ability to inhibit IL-8 production could enhance the treatment
      of liver diseases. Paeoniflorin is a major active constituent of dried Paeoniae
      Radix Alba root (Baishao in Chinese) which is widely used in China to treat liver
      diseases. We examined the effects and underlying mechanisms of paeoniflorin on IL
      8 production in primary human hepatic sinusoidal endothelial cells (HHSECs).
      Concanavalin A (ConA) at 20 MUg/mL produced a 5.2-fold increase in IL-8 mRNA by
      8h, and a 14.2-fold rise in IL-8 levels by 16 h. Inhibition of MEK (ERK kinase)
      and extracellular signal-regulated kinase (ERK) by PD98059 and U0126, or
      inhibition of phosphatidylinositol 3-kinase (PI3K) by LY294002 blocked both ConA
      induced IL-8 mRNA expression and IL-8 secretion. Paeoniflorin reduced ConA
      induced IL-8 mRNA expression and IL-8 release by 57.9% and 52.8%, respectively,
      and also decreased ConA-stimulated phosphorylation of ERK1/2 and Akt, suggesting
      paeoniflorin inhibits IL-8 expression and release by inhibiting the ERK1/2 and
      Akt pathways. Combining paeoniflorin with U0126 or LY294002 at low doses showed
      supra-additive inhibition of not only phospho-ERK1/2 and phospho-Akt by 46.4% and
      35.0%, but also IL-8 release by 42.4% and 36.1% and IL-8 mRNA expression by 43.5%
      and 31.8%, respectively. In conclusion, paeoniflorin most likely contributes to
      the therapy for liver disease by exerting anti-inflammatory effects on HHSECs
      through blocking IL-8 secretion via downregulation of ERK1/2 and Akt
      phosphorylation.

PMID- 25748731
TI  - Therapeutic effects of Lactobacillus in treating irritable bowel syndrome: a meta
      analysis.
AB  - OBJECTIVE: As the lack of reliable treatment for irritable bowel syndrome (IBS)
      prompts interest in the development of new therapies, we aimed to systematically
      evaluate the effect of Lactobacillus in treating this disease. METHODS: We
      searched MEDLIINE, PubMed, Scopus, Web of Science and the Cochrane Central
      Register of Controlled Trials for the period from 1966 to August 2013 for double
      blind, placebo-controlled trials investigating the efficacy of Lactobacillus
      treatment in the management of IBS. The studies were screened for inclusion based
      on randomization, controls and reported measurable outcomes. We used the Jadad
      score to assess the quality of the articles. The STATA 11.0 and Revman 5.0
      software packages were used for the meta-analysis. The STATA 11.0 software
      program was also used to assess indicators of publication bias according to
      Begg's and Egger's tests. RESULTS: Six randomized, placebo-controlled clinical
      trials met the criteria and were included in the meta-analysis. The Jadad score
      of the articles was >3, and three articles were of high quality. We analyzed the
      heterogeneity of the studies and found no heterogeneity in the meta-analysis. In
      the forest plot, the diamond was on the right side of the vertical line and did
      not intersect with the line. The pooled relative risk for clinical improvement
      with Lactobacillus treatment was 7.69 (95% confidence interval: 2.33-25.43,
      p=0.0008). For adults, the pooled relative risk for clinical improvement with
      Lactobacillus treatment was 17.62 (95% confidence interval: 5.12-60.65,
      p<0.00001). For children, the pooled relative risk for clinical improvement with
      Lactobacillus treatment was 3.71 (95% confidence interval:1.05-13.11, p=0.04).
      Using the STATA 10.0 and Revman 5.0 software programs, we confirmed that
      Lactobacillus exhibited significant efficacy in treating IBS. CONCLUSION:
      Compared with the placebo, Lactobacillus treatment was found to be associated
      with a significantly higher rate of treatment responders in the overall
      population with IBS, without any side effects. As to limitations of the analysis,
      additional research is needed.

PMID- 25748732
TI  - XPD Lys751Gln polymorphisms and the risk of esophageal cancer: an updated meta
      analysis.
AB  - OBJECTIVE: Published data regarding the association between xeroderma pigmentosum
      group D XPD Lys751Gln polymorphisms and esophageal cancer (EC) cancer remain
      controversial. The present meta-analysis aimed to obtain a more precise
      estimation of the relationship between XPD Lys751Gln polymorphisms and the risk
      of EC. METHODS: All eligible case-control studies of Lys751Gln polymorphisms and
      susceptibility to EC were selected from PubMed, Web of Science and CNKI up to
      October 2013. The data were extracted, and pooled odds ratios (ORs) with 95%
      confidence intervals (CIs) were calculated. RESULTS: A total of 21 case-control
      studies from 19 reports were assessed in this meta-analysis, including 6,581
      cases and 8,251 controls. There was a significant association between the XPD
      Lys751Gln polymorphism and the risk of esophageal cancer in the overall
      population (Dominant model: OR=1.30, 95%CI: 1.07-1.57, p<0.05; Lys/Gln vs.
      Gln/Gln: OR=1.20, 95%CI: 1.05-137, p<0.05; Gln/Gln vs. Lys/Lys: OR=1.76, 95%CI:
      1.08-2.85, p=0.02; Recessive model: OR=1.48, 95%CI: 1.06-2.07, p=0.02). Similar
      results were found when stratified according to the cancer type, ethnicity and
      control source. However, no associations were found among smokers or drinkers.
      CONCLUSION: The results of this meta-analysis suggest that XPD Lys751Gln
      polymorphisms contribute to susceptibility to EC.

PMID- 25748733
TI  - Efficacy of combined balloon-occluded retrograde transvenous obliteration and
      simultaneous endoscopic injection sclerotherapy.
AB  - OBJECTIVE: We evaluated the efficacy and safety of balloon-occluded retrograde
      transvenous obliteration (B-RTO) performed using absolute ethanol with iodized
      oil (ET+LPD) and simultaneous endoscopic injection sclerotherapy (EIS) with
      cyanoacrylate (CA) for gastric varices (GVs). METHODS: A total of 16 patients
      with endoscopically proven high-risk GVs treated using combined B-RTO with ET+LPD
      and EIS with CA between January 2007 and July 2012 were enrolled. RESULTS: Twelve
      cases included GVs involving both the cardia and fundus, two cases included
      fundal varices and two cases included cardiac varices. In terms of the form of
      GVs, 10 cases involved F2 lesions and six cases involved F3 lesions. The flow
      vein was the left gastric vein in 13 cases and the posterior gastric vein in
      three cases. The drainage route was a splenorenal shunt in all cases. The average
      dose of ET+LPD was 12.0 mL, while that of CA was 2.45 mL. All complications were
      transient, and no major complications occurred after the procedures. None of the
      patients experienced bleeding or recurrence of gastric varices after the combined
      B-RTO and EIS procedures during an average follow-up period of 38.3 months.
      CONCLUSION: Combined B-RTO with ET+LPD and simultaneous EIS with CA is considered
      to be an effective and safe procedure for treating GVs.

PMID- 25748734
TI  - Perioperative complications of endoscopic submucosal dissection for early gastric
      cancer in elderly Japanese patients 75 years of age or older.
AB  - OBJECTIVE: The number of endoscopic submucosal dissection (ESD) procedures for
      early gastric cancers among patients 75 years of age or older has been
      increasing. We herein examined both the outcomes and complications of ESD in
      elderly patients. METHODS: We investigated the effects of underlying diseases,
      lesion characteristics, treatment outcomes and complications during and in the
      postoperative periods of ESD among elderly patients 75 years of age or older
      versus non-elderly patients less than 75 years of age. Patients A total of 318
      early gastric cancers in consecutive 307 patients, all of whom underwent ESD for
      gastric cancer, were included in this study. RESULTS: The number of patients with
      hypertension and ischemic heart disease was significantly higher in the elderly
      group than in the non-elderly group. The proportion of lesions with an absolute
      indication, extended indication or no indication was not significantly different
      between the groups. During the ESD procedure, the use of atropine sulfate for
      bradycardia was significantly more frequent in the elderly group. No significant
      differences were observed between the groups in terms of the treatment for
      hypertension, oxygen administration or incidence of perforation. In addition,
      there were no significant differences with respect to oxygen administration,
      postoperative bleeding or the occurrence of fever and/or pneumonia after the ESD
      procedure. CONCLUSION: Although bradycardia was more frequently observed in the
      elderly patients during ESD in this study, ESD was performed safely and managed
      appropriately, with infrequent postoperative complications. ESD appears to be
      effective, even in elderly patients.

PMID- 25748735
TI  - Long-term pegylated interferon monotherapy following 72 weeks of pegylated
      interferon and ribavirin in hepatitis C virus genotype-1-infected slow
      responders.
AB  - OBJECTIVE: Slow responders to pegylated interferon (Peg-IFN) and ribavirin (RBV)
      among patients infected with hepatitis C virus (HCV) genotype 1 may benefit from
      an extended treatment course. The aim of this study was to determine the efficacy
      of persistent negative serum HCV RNA over 96 weeks during long-term Peg-IFN
      monotherapy following 72 weeks of combination therapy. METHODS: A total of 46 HCV
      genotype 1-infected slow responders were treated for 72 weeks with Peg-IFN and
      RBV combination therapy alone (n=25) or additional long-term biweekly treatment
      with 90 MUg of Peg-IFN-alpha2a (n=21). The criterion for the completion of long
      term Peg-IFN monotherapy was defined as the attainment of constantly negative HCV
      RNA in the serum over 96 weeks during IFN treatment. RESULTS: The patients with
      sustained negative serum HCV RNA during 96 weeks of IFN treatment had a higher
      rate of sustained virological response (SVR) than those without (81 vs. 40%,
      p=0.012). A multivariate analysis identified sustained negativity of serum HCV
      RNA over 96 weeks of IFN treatment to be a predictive factor for SVR. CONCLUSION:
      In the present study, sustained negative serum HCV RNA over 96 weeks during long
      term Peg-IFN monotherapy following 72 weeks of combination therapy of Peg-IFN and
      RBV resulted in beneficial virological outcomes among HCV genotype 1-infected
      slow responders.

PMID- 25748736
TI  - One of six patients with non-ischemic heart disease exhibit provoked coronary
      spasms: non-ischemic heart disease associated with ischemia?
AB  - OBJECTIVE: The majority of cardiologists do not perform spasm provocation tests
      in patients with non-ischemic heart disease (non-IHD) or non-obstructive coronary
      artery disease (non-ob-CAD). We herein examined the frequency of provoked spasms
      in non-IHD and non-ob-CAD patients, including those with atypical chest pain
      (Aty), valvular heart disease (Val), hypertrophic cardiomyopathy (HCM),
      congestive heart failure (CHF), and others (Oth). METHODS & RESULTS: We performed
      acetylcholine (ACh) spasm provocation tests over a period of 22 years (1991-2012)
      among 1,440 patients, including 981 IHD and 459 non-IHD subjects. A total of 43
      patients with significant organic stenosis were excluded, and the remaining 416
      patients with non-IHD or non-ob-CAD disease were assessed. ACh was injected in
      incremental doses of 20/50/80 MUg into the right coronary artery (RCA) and
      20/50/100/(200) MUg into the left coronary artery (LCA). Positive coronary spasms
      were defined as transient luminal narrowing of >99%. Positive coronary spasms
      were noted in 17.3% of the non-IHDs patients (72/416), compared to 11.4%
      (15/132), 19% (8/42), 16.7% (5/30), 23.9% (16/67), and 19.3% (28/145), in the
      patients in the Aty, Val, HCM, CHF, and Oth groups, respectively. The rate of
      positive provoked spasms was higher in men than women, although not significantly
      [20.6% (46/223) vs. 13.4% (26/193), ns], and significantly higher in the late
      period (2001-2012) than in the early period (1991-2000) (36.8% vs. 7.0%,
      p<0.001). CONCLUSION: Physicians should perform spasm provocation tests in
      patients with IHD as well as non-IHD with non-ob-CAD, as one of six non-IHD
      patients in this study exhibited provoked coronary spasms.

PMID- 25748737
TI  - Associations SELE gene haplotype variant and hypertension in Mongolian and Han
      populations.
AB  - Genetic variation is thought to contribute to the etiology of hypertension, and E
      selectin is a candidate essential hypertension-associated gene. OBJECTIVE: In
      this study, we attempted to test the hypothesis that subtle haplotype variants of
      SELE genes may be sources of essential hypertension in Mongolian and Han
      populations. MATERIALS: A total of 429 unrelated Mongolian herdsmen and 416 Han
      farmers were enrolled, including 212 Mongolian essential hypertension (EH)
      patients, 217 Mongolian normotensives (controls), 200 Han EH patients and 216 Han
      normotensives (controls). METHODS: All nine tag single-nucleotide polymorphisms
      (SNPs) within the SELE gene were retrieved from HapMap and the genotyping was
      performed using a polymerase chain reaction (PCR)/ligase detection reaction
      assay. Results The distributions of the A-allele frequency of rs3917458 and the C
      allele frequency of rs2179172 differed significantly between the hypertensive
      subjects and controls in the Han population. The frequency of haplotype GGC was
      significantly higher in the EH group than in the controls in the Mongolian
      population. In the Han population, a significant difference was observed in the
      haplotype frequency of TCC between the patients and controls, whereas haplotype
      ACA was detected significantly less often in the EH subjects than in the
      controls. CONCLUSION: Meanwhile, the haplotype TCC in the Han hypertensive
      patients and the haplotype GGC in the Mongolian patients had independent effects
      in increasing the risk for EH and maybe used as risk factors for predicting high
      blood pressure. However, the haplotype ACA had an independent effect in
      decreasing the risk of hypertension and may be protective in normotensive
      subjects in the Han population. Therefore, multiple SNPs in combination in SELE
      may confer a risk of hypertension.

PMID- 25748739
TI  - Lifestyle interventions for adults with impaired glucose tolerance: a systematic
      review and meta-analysis of the effects on glycemic control.
AB  - OBJECTIVE: Previous meta-analyses have demonstrated that lifestyle modification
      can reduce the blood glucose levels in patients with type 2 diabetes, although
      the effects of changes in the blood glucose level on impaired glucose tolerance
      (IGT) remain controversial. This review therefore aimed to determine the efficacy
      of lifestyle interventions in adults with IGT. METHODS: We searched the Medline,
      Cochrane Library, EMBASE and Science Citation Index databases and reference lists
      of the included articles. Two independent reviewers extracted the data and
      assessed the quality of the included studies; a total of nine randomized
      controlled trials met the inclusion criteria. In addition, we tested for trial
      heterogeneity and calculated the pooled effects size using the random effects
      model. RESULTS: The overall interventions were associated with a decline in the 2
      hour plasma glucose levels [standardized mean differences (SMD) -0.56; 95%
      confidence interval (CI), -1.01 to -0.10; I(2), 96.6%]. Moreover, dietary
      intervention (SMD -0.53; 95% CI -0.77 to -0.28) and physical intervention (SMD 
      0.42; 95% CI -0.63 to -0.20) were each associated with a decline in the 2-hour
      plasma glucose levels compared with that observed in the control participants.
      The overall interventions were associated with a decline in the fasting plasma
      glucose (FPG) levels (SMD -0.27; 95% CI -0.38 to -0.15; I(2) = 47.1%). In
      addition, physical intervention (SMD -0.25; 95% CI -0.44 to -0.05) and combined
      dietary and physical intervention were each associated with a decreased FPG level
      (SMD -0.28; 95% CI -0.44 to -0.12) compared with that observed in the control
      participants. CONCLUSION: Lifestyle modification based on physical or dietary
      interventions or both is associated with improvements in the 2-hour plasma
      glucose and FPG levels in IGT patients.

PMID- 25748738
TI  - Effects of a high salt intake and potassium supplementation on QT interval
      dispersion in normotensive healthy subjects.
AB  - OBJECTIVE: To evaluate the effects of dietary sodium intake on QT interval
      dispersion (QTd) in normotensive healthy subjects and assess the protective
      effects of dietary potassium. Methods All subjects were sequentially maintained
      on a protocol with a three-day baseline investigation, seven-day low-salt period
      (3 g/day (d), NaCL), seven-day salt loading period (18 g/d, NaCL) and a seven-day
      salt loading with potassium supplementation period (4.5 g/d, KCL). On the last
      day of each period, 24-hour urine samples were collected, the blood pressure
      values were measured and an electrocardiogram was recorded. The QT interval, QTd
      and T peak-T end interval (Tp-Te) were subsequently measured and calculated.
      Patients Sixty-four normotensive subjects, men and women, ranging from 28 to 60
      years of age, were enrolled. Results There were no great fluctuations in heart
      rate after salt loading, whereas the systolic blood pressure (SBP, mmHg) and
      diastolic blood pressure (DBP, mmHg) increased and the corrected QT interval
      (QTc), corrected QT interval dispersion (QTdc) and Tp-Te values were
      significantly prolonged compared to that observed in the low-salt period (SBP,
      118.6 +/- 13.5 vs. 111.7 +/- 11.3, p<0.01; DBP, 76.9 +/- 8.6 vs. 71.7 +/- 7.7,
      p<0.01; QTdc, 60.3 +/- 19.4 vs. 55.6 +/- 19.4, p<0.05; Tp-Te, 83.0 +/- 10.1 vs.
      79.8 +/- 8.5, p<0.01). Surprisingly, all of these changes were reversed by
      potassium supplementation (SBP, 114.5 +/- 12.3 vs.118.6 +/- 13.5, p<0.01; DBP,
      72.2 +/- 7.9 vs.76.9 +/- 8.6, p<0.01;QTd, 42.6 +/- 15.1 vs. 47.4 +/- 19.0,
      p<0.05; QTdc, 52.2 +/- 18.0 vs. 60.3 +/- 19.4, p<0.05; Tp-Te, 79.1 +/- 8.5 vs.
      83.0 +/- 10.1, p<0.01). Conclusion Salt loading prolongs the QT interval, QTd and
      Tp-Te, while dietary potassium supplementation reverses these alterations. These
      findings suggest that potassium supplementation may improve variation in the
      healing time and prevent arrhythmia.

PMID- 25748740
TI  - High salt intake is associated with renal involvement in Japanese patients with
      type 2 diabetes mellitus.
AB  - OBJECTIVE: The aim of our study was to investigate clinical and nutritional
      factors associated with renal involvement in patients with type 2 diabetes.
      PATIENTS: We performed a cross-sectional study of 71 patients with type 2
      diabetes who were being educated at our hospital from September 2006 to February
      2008. The patients were divided into two groups; Group I consisted of 40 patients
      with both an estimated glomerular filtration rate (eGFR) of >= 60 mL/min/1.73
      m(2) and normoalbuminuria, and Group II consisted of 31 patients with either
      microalbuminuria/overt proteinuria or an eGFR of <60 mL/min/1.73 m(2). We
      compared the age, body mass index (BMI), blood pressure, duration from onset of
      diabetes, use of hypoglycemic agents and insulin, biochemistry data, including
      HbA1c, pulse wave velocity corrected by blood pressure (PWVc) and the daily
      intake of several nutrients between the two groups. A multivariate logistic
      regression analysis was performed to identify factors independently associated
      with renal involvement. RESULTS: Group II had significantly higher values for
      BMI, the duration of diabetes, triglycerides, uric acid and PWVc than Group I.
      Group II tended to have a high salt intake compared to Group I. The multivariate
      logistic analysis revealed that the daily salt intake, PWVc and uric acid were
      independent factors associated with renal involvement (odds ratio, 1.15, 1.84 and
      2.00; 95% confidence interval, 1.02-1.31, 1.04-3.27 and 1.04-3.85, respectively).
      CONCLUSION: Our data suggest that a high salt intake, in addition to
      arteriosclerosis, is associated with renal involvement in our cohort with type 2
      diabetes.

PMID- 25748741
TI  - Diffuse alveolar hemorrhage with predominantly right-sided infiltration resulting
      from cardiac comorbidities.
AB  - OBJECTIVE: Radiographic findings in patients with diffuse alveolar hemorrhage
      (DAH) are usually diffuse and bilateral, although they may occasionally be
      unilateral. The clinical aspects of predominantly unilateral DAH are not well
      known. Therefore, our objective was to describe the clinical characteristics of
      predominantly right-sided DAH. METHODS: We retrospectively reviewed data for 460
      bronchoalveolar lavage fluid (BALF) samples collected between January 2009 and
      July 2013. Patients who presented with increasingly hemorrhagic BALF were
      diagnosed with DAH, and unilateral predominance was determined based on the
      degree of infiltration on chest radiographs. RESULTS: The records of 54 patients
      with DAH were evaluated. The leading etiology was pulmonary congestion due to
      heart failure (n=15). The radiographs showed right-sided infiltration in 18
      patients (33%), left-sided infiltration in six patients (11%) and bilateral
      infiltration in 30 patients (56%). Predominantly right-sided DAH was often caused
      by pulmonary congestion resulting from heart failure (10 of 18 patients). A
      multivariate logistic regression analysis revealed a previous history of
      cardiovascular disease to be the only significant predictor of right-sided DAH
      (OR 13.1, 95% CI 2.9-95.4). CONCLUSION: Predominantly right-sided DAH is
      frequently caused by pulmonary congestion resulting from heart failure and is
      significantly related to comorbidities with cardiovascular disease.

PMID- 25748742
TI  - Multiple primary malignancies in patients with non-small cell lung cancer.
AB  - OBJECTIVE: Information regarding multiple primary malignancies is important, as
      it has the potential to clarify etiological factors and may indicate the need to
      refine patient follow-up to include screening for associated malignancies. Upper
      aerodigestive tract cancer often develops in patients with smoking-related lung
      cancer; however, little is known about the frequencies or types of other primary
      malignancies in patients with non-small cell lung cancer (NSCLC) without a
      history of smoking. METHODS: We retrospectively evaluated the records of patients
      examined and/or treated for NSCLC at the Institute of Biomedical Research and
      Innovation between January 2007 and June 2012. Patients In total, 938 patients,
      including 599 men (never-smoker/ever-smoker: 35/564) and 339 women (never
      smoker/ever-smoker: 236/103), were analyzed. RESULTS: Among the 209 patients
      (22.3%) with multiple primary malignancies, 151 had a history of smoking and 58
      were never-smokers. The most common cancers were gastric (43 cases), colorectal
      (33 cases), and prostate (29 cases) cancer. Smoking-related cancer was more
      common in current smokers and ex-smokers for both men and women. Among women with
      NSCLC, never-smokers were more likely to have thyroid cancer than those with a
      history of smoking (5.1% vs. 0%, p=0.021). CONCLUSION: In this study, several
      differences in malignancies were observed between never-smokers and patients with
      a history of smoking. Thyroid cancer and NSCLC co-existed in some women without a
      history of smoking, implicating predisposing factors other than tobacco smoke in
      the onset of these cancers.

PMID- 25748744
TI  - Multi-organ involvement of Sweet's syndrome: a case report and literature review.
AB  - The hallmark of Sweet's syndrome (SS) is the infiltration of mature neutrophils
      in the upper dermis. We herein report a case of SS with multi-organ involvement.
      A 32-year-old man presented with fever, anemia and dyspnea. He was given
      antibiotics, without any improvements. Later, a number of erythematous lesions
      appeared, accompanied by deteriorating respiratory and cardiovascular functions.
      A diagnosis of SS was confirmed on a skin biopsy, and the patient was given
      corticosteroids, the dose of which was reduced after one month. The organ
      function subsequently deteriorated, and he ultimately died of multi-organ
      failure. Early recognition of SS with multi-organ involvement is important in
      patients with SS. 

PMID- 25748743
TI  - Effects of Waon therapy on chronic fatigue syndrome: a pilot study.
AB  - OBJECTIVE: Chronic fatigue syndrome (CFS) is a disabling condition of unknown
      etiology, and no definitive therapy has been identified to date. We developed
      Waon therapy, a form of thermal therapy using a far-infrared dry sauna, and in
      this study herein examined its feasibility and safety in patients with CFS.
      METHODS: Ten consecutive inpatients with CFS stayed in a 60 degrees C sauna for
      15 minutes and then rested on a bed under a blanket for an additional 30 minutes
      outside the sauna room. The treatments were performed once a day, five days a
      week for four weeks. Perceived fatigue, the primary outcome measure, was
      evaluated using a numerical rating scale before, during (two weeks after the
      commencement of therapy) and after therapy. The pain level, evaluated using a
      numerical rating scale, mood, assessed using the Profile of Mood States
      questionnaire, and performance status, assessed using a scale developed for CFS
      patients were also examined before and after therapy. RESULTS: Perceived fatigue
      significantly decreased after therapy, although no significant reductions were
      observed during therapy. In addition, a negative mood, including anxiety,
      depression and fatigue, and the performance status significantly improved after
      therapy. However, the levels of pain and vigor did not change significantly. No
      patients reported any adverse effects during the therapy. CONCLUSION: These
      findings suggest that Waon therapy may be a useful and safe treatment for CFS.

PMID- 25748745
TI  - Guillain-Barre syndrome variant with facial diplegia and paresthesias associated
      with IgM anti-GalNAc-GD1a antibodies.
AB  - We herein report the case of a 19-year-old woman with facial diplegia and
      paresthesias (FDP) preceded by flu-like symptoms. We diagnosed the patient with a
      regional variant of Guillain-Barre syndrome due to decreased tendon reflexes,
      albuminocytological dissociation in the cerebrospinal fluid and demyelinating
      features on nerve conduction studies. The patient also had IgM anti-GalNAc-GD1a
      antibodies, and treatment with glucocorticoids was effective for treating the
      facial diplegia, but not paresthesia. Therefore, facial palsy may have a
      different pathophysiology from paresthesia or other symptoms of FDP, which
      responds to glucocorticoid therapy. 

PMID- 25748746
TI  - Large spontaneous rectus sheath hematoma associated with severe anemia.

PMID- 25748747
TI  - Primary lung sebaceous carcinoma.

PMID- 25748748
TI  - Interstitial pulmonary amyloidosis with Waldenstrom's macroglobulinemia.

PMID- 25748749
TI  - Novel cord-like structures on MRI in a case of hypervirulent Klebsiella
      pneumoniae.

PMID- 25748750
TI  - Hypertrophic osteoarthropathy associated with esophageal cancer.

PMID- 25748751
TI  - The myelinated fiber loss in the corpus callosum of mouse model of schizophrenia
      induced by MK-801.
AB  - Previous magnetic resonance imaging (MRI) and diffusion tensor imaging (DTI)
      investigations have shown that the white matter volume and fractional anisotropy
      (FA) were decreased in schizophrenia (SZ), which indicated impaired white matter
      integrity in SZ. However, the mechanism underlying these abnormalities has been
      less studied. The current study was designed to investigate the possible reasons
      for white matter abnormalities in the mouse model of SZ induced by NMDA receptor
      antagonist using the unbiased stereological methods and transmission electron
      microscope technique. We found that the mice treated with MK-801 demonstrated a
      series of schizophrenia-like behaviors including hyperlocomotor activity and more
      anxiety. The myelinated fibers in the corpus callosum (CC) of the mice treated
      with MK-801 were impaired with splitting lamellae of myelin sheaths and segmental
      demyelination. The CC volume and the total length of the myelinated fibers in the
      CC of the mice treated with MK-801 were significantly decreased by 9.4% and 16.8%
      when compared to those of the mice treated with saline. We further found that the
      loss of the myelinated fibers length was mainly due to the marked loss of the
      myelinated nerve fibers with the diameter of 0.4-0.5 MUm. These results indicated
      that the splitting myelin sheaths, demyelination and the loss of myelinated
      fibers with small diameter might provide one of the structural bases for impaired
      white matter integrity of CC in the mouse model of SZ. These results might also
      provide a baseline for further studies searching for the treatment of SZ through
      targeting white matter. 

PMID- 25748752
TI  - Some personality traits converge gradually by long-term partnership through the
      lifecourse--genetic and environmental structure of Cloninger's temperament and
      character dimensions.
AB  - Temperament and Character Inventory (TCI) is a comprehensive personality
      inventory that is widely used in behavioral genetics. The original theory
      suggested that temperament traits were under genetic influences, whereas
      character traits were gradually built by an interaction between temperaments and
      environment until early adulthood. This study attempted to evaluate TCI by
      examining the genetic and environmental contributions to personality with
      particular attention to spousal effects. From 687 families, a total of 3459
      Korean adult individuals completed the survey. Among them, there were 542
      Monozygotic (MZ) twin pairs and 122 Dizygotic twin pairs. Intraclass correlation
      coefficients (ICCs) and heritability were calculated to examine the genetic and
      shared environmental contributions to personality. Moderate genetic contributions
      (0.17-0.43) were found for all TCI traits along with the evidence of shared
      environment (0.11-0.31) for harm avoidance (HA) and all characters. The ICCs of
      TCI in MZ pairs ranged 0.36-0.46. Spouses' had little resemblance for
      temperament, whereas for character dimensions, spouses (0.27-0.38) were more
      similar than first degree relatives (0.10-0.29). Resemblance between spouses
      increased with duration of marriage for most characters and HA. When the growing
      similarities between spouses were compared with their MZ cotwins' for subgroup of
      81 trios, self-directedness (SD) of character showed even more similarities
      toward their spouses than cotwins as partnership duration increased (r = 0.32).
      Our findings with regard to change in SD into late adulthood support the
      psychobiological theory of temperament and character, which suggests that both
      personality domains have distinct developmental trajectories despite equally
      large genetic influences. 

PMID- 25748753
TI  - Corpus callosum atrophy associated with the degree of cognitive decline in
      patients with Alzheimer's dementia or mild cognitive impairment: a meta-analysis
      of the region of interest structural imaging studies.
AB  - Individual structural neuroimaging studies of the corpus callosum (CC) in
      Alzheimer's disease (AD) and mild cognitive impairment (MCI) with the region of
      interest (ROI) analysis have yielded inconsistent findings. The aim of this study
      was to conduct a meta-analysis of structural imaging studies using ROI technique
      to measure the CC midsagittal area changes in patients with AD or MCI. Databases
      of PubMed, the Cochrane Library, the ISI Web of Science, and Science Direct from
      inception to June 2014 were searched with key words "corpus callosum" or
      "callosal", plus "Alzheimer's disease" or "mild cognitive impairment". Twenty
      three studies with 603 patients with AD, 146 with MCI, and 638 healthy controls
      were included in this meta-analysis. Effect size was used to measure the
      difference between patients with AD or MCI and healthy controls. Significant
      callosal atrophy was found in MCI patients with an effect size of -0.36 (95% CI, 
      0.57 to -0.14; P = 0.001). The degree of the CC atrophy in mild AD was less
      severe than that in moderate AD with a mean effect size -0.69 (95% CI, -0.89 to 
      0.49) versus -0.92 (95% CI, -1.16 to -0.69), respectively. Comparing with healthy
      controls, patients with MCI had atrophy in the anterior portion of the CC (i.e.,
      rostrum and genu). In contrast, patients with AD had atrophy in both anterior and
      posterior portions (i.e., splenium). These results suggest that callosal atrophy
      may be related to the degree of cognitive decline in patients with MCI and AD,
      and it may be used as a biomarker for patients with cognitive deficit even before
      meeting the criteria for AD. 

PMID- 25748754
TI  - Data supporting key components of family medicine-scope, continuity,
      interprofessional care, and more.
AB  - This issue contains multiple articles supporting key components of family
      medicine, either evidence that these components are important, or strategies to
      implement them in practice. For examples, see the articles on interprofessional
      care,(1-5) continuity,(6) cultural competence,(7) continuing competence,(8,9) and
      provision of essential care to the underserved.(10) We provide additional insight
      into how different physicians interpret similar data on older patients.(11) We
      have broad physician input into potential items to be considered in the national
      Choosing Wisely campaign, with many excellent interventions identified that
      should be performed less often.(12) However, choosing wisely for the United
      States population should also require adequate payment to encompass the breadth
      of what family physicians can and want to do to improve health for and with their
      patients.(13) All the articles relate to improving quality and cost of health
      care. 

PMID- 25748755
TI  - Patient empanelment: the importance of understanding who is at home in the
      medical home.

PMID- 25748756
TI  - Only one third of family physicians can estimate their patient panel size.
AB  - In addition to payments for services rendered to individual patients, primary
      care physicians will increasingly be paid for their ability to achieve goals
      across the body of patients most closely associated with them: their "panel." In
      a 2013 survey, however, only one third of family physicians could estimate their
      panel size, raising concern about their ability to perform more advanced primary
      care functions. 

PMID- 25748757
TI  - Use of and interests in complementary and alternative medicine by Hispanic
      patients of a community health center.
AB  - INTRODUCTION: We evaluated complementary and alternative medicine (CAM) use among
      a medically underserved, predominately Hispanic community at the University of
      California Irvine Family Health Center, a federally qualified health center.
      METHODS: A cross-sectional, anonymous survey assessed patient use of, interest
      in, and communication preferences concerning CAM. RESULTS: The 150 respondents
      primarily self-identified as Hispanic (74%), were born outside the United States
      (55%), were medically insured (56%), and had a high school education or less
      (55%). Of these respondents, 63% used at least 1 type of CAM; the most commonly
      used were: vitamins/supplements (32%), herbal medicine (29%), dietary/nutritional
      therapy (26%), massage (24%), meditation/relaxation (15%) and chiropractic (11%).
      Therapies that patients most desired to see provided at the clinic included
      massage, healthier cooking, guidance on herbs/supplements, and diet/nutrition.
      Among respondents, 61% were comfortable disclosing CAM use to physicians, 58%
      agreed physicians should have basic knowledge of CAM, and 47% desired that
      physicians ask about CAM use. CONCLUSIONS: Results demonstrate that CAM use is
      common among patients, and a large proportion of patients have interest in
      accessing CAM through their primary care clinic. Patients recognize the
      importance of communicating CAM use with their providers and seem receptive to
      discussing such topics.

PMID- 25748758
TI  - Patient-oriented evidence that matters (POEMs)TM suggest potential clinical
      topics for the Choosing WiselyTM campaign.
AB  - OBJECTIVE: We propose a method of identifying clinical topics for campaigns like
      Choosing Wisely. METHODS: In the context of an ongoing continuing medication
      education program, we analyzed ratings on every patient-oriented evidence that
      matters (POEM) synopsis delivered in 2012 and 2013. Given the objective of the
      Choosing Wisely campaign, we focused this analysis on 1 specific item in the
      validated questionnaire used by physicians to rate POEMs. This questionnaire item
      is about "avoiding an unnecessary diagnostic test or treatment." For each POEM,
      we calculated frequencies and proportions for this item, then we identified the
      20 POEMs that were most commonly associated with this item in 2012 and 2013.
      Finally, we determined whether the clinical topic of each of these POEMs was
      mentioned in the Choosing Wisely master list. RESULTS: In 2012 and 2013 we
      received 506,809 completed questionnaires (or ratings) linked to 530 POEMs, for
      an average of 956 ratings per POEM. In 59% of these POEMs (n = 312), the most
      commonly expected type of health benefit was "avoiding an unnecessary diagnostic
      test or treatment." We then identified the top 20 POEMs most commonly associated
      with this item in each year by ranking all 312 POEMs from the top down. The
      clinical topic addressed by 29 of these 40 POEMs was not addressed in the
      Choosing Wisely master list. These topics fell into 3 categories: diagnostic
      tests, medical interventions, and surgical interventions. CONCLUSION: "Big data"
      can identify clinical topics relevant to campaigns such as Choosing Wisely. This
      process represents a new way to inform the expert panel approach.

PMID- 25748759
TI  - Insights from exemplar practices on achieving organizational structures in
      primary care.
AB  - PURPOSE: Interprofessional practice (IPP) is associated with better patient care
      outcomes and patient and provider satisfaction, yet little is known about the
      organizational structures that support effective IPP. METHODS: We selected 9
      diverse clinical practice sites with exemplary IPP and conducted site visits with
      nonparticipant observations and interviewed 80 physicians, nurses, pharmacists,
      dieticians, medical and hospital assistants, nurse practitioners, physician
      assistants, clinic managers, physical and occupational therapists, respiratory
      therapists, social workers, psychologists, and others. We independently coded
      field notes and interviews and identified themes and trends using a grounded
      theory approach. Sites were evaluated for IPP using key features identified by
      the 2011 Interprofessional Education Collaboration Expert Panel. RESULTS: The
      primary themes at sites with high IPP were coordination of care and mutual
      respect. Four key organizational features were associated with these 2 themes:
      independent responsibilities for each professional; organizational structures for
      providers to learn about each other's roles; a structure and culture promoting
      accessible, frequent communication about patients; and strong leadership in IPP
      supportive values. CONCLUSIONS: To achieve interprofessional collaboration,
      practice teams require structural supports that facilitate coordination of care
      and mutual respect.

PMID- 25748760
TI  - Improving acute respiratory infection care through nurse phone care and academic
      detailing of physicians.
AB  - INTRODUCTION: To address unnecessary use of antibiotics for uncomplicated acute
      respiratory infection, we implemented a standardized care pathway composed of:
      (1) academic detailing of primary care providers, and (2) telephonic care from
      nurses. METHODS: To evaluate the intervention, we performed a retrospective time
      series study and cost analysis at a primary care provider network in the Pacific
      Northwest with 118 providers at seven sites. The main outcomes were: (1)
      antibiotic rate, (2) provider visits avoided, and (3) cost savings from the payer
      and health care system perspectives. Data were collected for January 2, 2010 to
      November 30, 2013, with the interventions occurring on March 1, 2012. RESULTS:
      There were 54,283 acute upper respiratory infection visits (34,678 [64%] female;
      average age, 52.1 years). After the intervention, nurse phone consultation
      involved 13.8% (3,289 of 23,769) of care episodes. The intervention was
      associated with a 16.5% absolute decrease in antibiotic rate (95% CI, -0.205 to 
      0.125; P < .001), after adjustment. Post intervention, 1983 of 23,769 (8.3%)
      episodes did not require any provider visit (1133 per year). Single institution
      cost savings to payers exceeded $175,000. CONCLUSIONS: Implementation of nurse
      phone care and provider academic detailing was associated with lower
      inappropriate antibiotic usage and fewer unnecessary provider visits.

PMID- 25748761
TI  - Patient care outcomes of a tobacco use registry in an academic family practice.
AB  - PURPOSE: While the potential benefit of a chronic disease registry for tobacco
      use is great, outcome reports have not been generated. We examined the effect of
      implementing a tobacco use registry, including a decision support tool, on
      treatment outcomes within an academic family medicine clinic. METHODS: A chart
      review of 200 patients who smoked and attended the clinic before and after
      registry implementation assessed the number of patients with clinic notes
      documenting (1) counseling for tobacco use, (2) recommendations for cessation
      medication, (3) a set quit date, (4) referrals to the on-site Nicotine Dependence
      Program (NDP) and/or QuitlineNC, and (5) pneumococcal vaccine. Data from the NDP,
      QuitlineNC, and clinic billing records before and after implementation compared
      the number of clinic-generated QuitlineNC fax referrals, new scheduled
      appointments for the NDP, and visits coded for tobacco counseling reimbursement.
      RESULTS: Significant increases in documentation occurred across most chart review
      variables. Significant increases in the number of clinic-generated fax referrals
      to QuitlineNC (from 27 to 96), initial scheduled appointments for the NDP (from
      84 to 148), and coding for tobacco counseling (from 101 to 287) also occurred
      when compared with total patient visits during the same time periods. Patient
      attendance at the NDP (52%) and acceptance of QuitlineNC services (31%) remained
      constant. CONCLUSIONS: The tobacco use registry's decision support tool increased
      evidenced-based tobacco use treatment (referrals, medications, and counseling)
      for patients at an academic family medicine clinic. This novel tool offers
      standardized care for all patients who use tobacco, ensuring improved access to
      effective tobacco use counseling and medication treatments.

PMID- 25748762
TI  - The implementation of a tobacco use registry in an academic family practice.
AB  - PURPOSE: Patients who use tobacco often are not provided evidence-based
      interventions because of barriers such as lack of time or expertise. Using a
      chronic disease model, we sought to improve delivery of care with an innovative
      decision support tool and a tobacco use registry. METHODS: We designed and
      implemented a decision support tool in an academic family medicine clinic. To
      assess barriers, we measured duration of visit and provider confidence (scale of
      0-10) in prescribing cessation medications before and after the introduction of
      the tool. We examined fidelity through daily counts of returned forms. RESULTS:
      No significant differences in mean office visit cycle times occurred for tobacco
      users (64.7 vs 63.1 minutes; P = .90) or between tobacco users and nontobacco
      users (63.1 vs 62.5 minutes; P = 1.00) before or after implementation of the
      decision support tool. Mean provider confidence in prescribing cessation
      medications increased significantly for nicotine inhalers (4.8 vs 6.4; P = .01),
      nicotine nasal spray (3.9 vs 5.5; P = .03) and combination nicotine replacement
      therapy (5.5 vs 6.2; P = .05). Two years after implementation, 88% of forms were
      filled out and returned daily, and >2200 tobacco users have been entered into the
      registry. CONCLUSIONS: The tobacco use decision support tool resulted in an
      increase in provider confidence in prescribing cessation medications without
      lengthening the duration of patients' visits, and the tool continues to be used
      routinely in the practice 2 years after introduction, indicating sustainability.
      The use of a tobacco use registry and decision support tool aids in standardizing
      care and overcoming barriers to cessation counseling.

PMID- 25748763
TI  - continuity of care and avoidable hospitalizations for chronic obstructive
      pulmonary disease (COPD).
AB  - BACKGROUND: Numerous studied suggest that better continuity of care could result
      in better health outcomes. However, few studies have examined the relationship
      between continuity of care and avoidable hospitalizations. METHODS: A
      retrospective cohort study design was adopted. We used secondary data analysis
      based on claim data regarding health care utilization under a universal coverage
      health insurance scheme in Taiwan. The study population included 3,015 subjects
      who were newly diagnosed with chronic obstructive pulmonary disease (COPD) in
      2006. The main outcome was COPD-related avoidable hospitalization, and the
      continuity of care index (COCI) was used to measure continuity of care. A
      logistic regression model was used to control for sex, age, low-income status,
      and health status. RESULTS: With regard to the effects of continuity of care on
      avoidable hospitalizations, dose-response trends were observed. The logistic
      regression model showed that after controlling for covariables, subjects in the
      low COCI group were 129% (adjusted odds ratio, 2.29; 95% confidence interval,
      1.26-4.15) more likely to undergo COPD-related avoidable hospitalizations than
      those in the high COCI group. CONCLUSIONS: Patients with COPD with higher
      continuity of care had a significantly lower likelihood of avoidable
      hospitalization. To prevent future hospitalizations, health policy stakeholders
      should encourage physicians and patients to develop long-term relationships to
      further improve their health outcomes.

PMID- 25748764
TI  - Unconscious biases: racial microaggressions in American Indian health care.
AB  - PURPOSE: This article reports on the prevalence and correlates of microaggressive
      experiences in health care settings reported by American Indian (AI) adults with
      type 2 diabetes mellitus (T2DM). METHODS: This community-based participatory
      research project includes two AI reservation communities. Data were collected via
      in-person article-and-pencil survey interviews with 218 AI adults diagnosed with
      T2DM. RESULTS: Greater than one third of the sample reported experiencing a
      microaggression in interactions with their health providers. Reports of
      microaggressions were correlated with self-reported history of heart attack,
      worse depressive symptoms, and prior-year hospitalization. Depressive symptom
      ratings seemed to account for some of the association between microaggressions
      and hospitalization (but not history of heart attack) in multivariate models.
      CONCLUSIONS: Microaggressive experiences undermine the ideals of patient-centered
      care and in this study were correlated with worse mental and physical health
      reports for AIs living with a chronic disease. Providers should be cognizant of
      these subtle, often unconscious forms of discrimination.

PMID- 25748765
TI  - Diagnosis of frailty after a Comprehensive Geriatric Assessment: differences
      between family physicians and geriatricians.
AB  - BACKGROUND: To compare the outcomes of Comprehensive Geriatric Assessments by
      family physicians and geriatricians. METHODS: An explorative observational study
      was conducted in six family practices (12 ambulatory family practitioners) and 1
      geriatric department (4 hospital-based geriatricians) from a university medical
      center in Nijmegen (the Netherlands). As participants, we included 587 patients
      aged 70 years and older and registered in the six family practices. The main
      outcome measures were the judgment on the following: 1) absence or presence of
      frailty and 2) the state (good-fair-poor) on 8 underlying domains (physical,
      medication, cognition, sensory, instrumental activities of daily living scale,
      mobility, mental, and social) according to family practitioners and geriatricians
      based on a Comprehensive Geriatric Assessment. RESULTS: Family physicians and
      geriatricians agreed on frailty absence/presence in 76% of cases. Geriatricians
      considered elderly more often frail than family physicians did (n = 294, 50% vs n
      = 213, 36%). Disagreement on frailty status was notably found in the patients who
      had less distinct, either poor or good, health states. Discordant frailty
      judgments, in which the geriatrician rated a person as frail and the family
      physicians did not, were related to geriatricians more often rating physical
      health as impaired. Further, geriatricians' judgments of frailty were more
      strongly related to impaired scores on the domains cognition, sensory, mobility,
      and mental compared with family physicians judgments: odds ratios 79.3 versus
      9.3, 7.6 versus 2.0, 25.0 versus 3.0, and 18.0 versus 2.2, respectively. Impaired
      physical health and problematic medication use had equally strong associations
      with frailty in geriatricians and family physicians: odds ratios of 11.5 versus
      10.4 and 2.4 versus 2.5, respectively. CONCLUSIONS: Geriatricians more often
      judge patients as frail compared with family physicians and seem to evaluate the
      available information differently. With increasing collaboration between primary
      and secondary care, understanding these differences becomes increasingly
      relevant.

PMID- 25748766
TI  - Magnesium intake and depression in adults.
AB  - BACKGROUND: Depression is a common and often disabling disorder. Magnesium
      supplementation has been linked to improvement in depressive symptoms, but
      consensus on the relationship between magnesium and depression has not been
      reached. METHODS: The purpose of this study was to test the existence of an
      association between dietary magnesium intake and depression in the adult US
      population. A cross-sectional, population-based data set (National Health and
      Nutrition Examination Survey) was used to explore the relationship of magnesium
      intake and depression in 8894 US adults (mean age, 46.1 years; 47.4% men) from
      2007 to 2010. Using logistic regression to model the relationship between the
      presence of depression (Patient Health Questionnaire score >=5) and low magnesium
      intake (<184 mg/day), we examined the risk ratio (RR) of magnesium intake and its
      95% confidence interval. RESULTS: After adjusting for all potential confounders,
      the strength of the association of very low magnesium intake with depression was
      statistically significant (RR = 1.16; 95% CI, 1.06-1.30). Adjusting for all other
      covariates, low magnesium intake was associated with depression in subjects
      younger than age 65 (RR, 1.22; 95% CI, 1.06-1.40; P = .007) but seemed to be
      protective in seniors (RR, 0.75; 95% CI, 0.56-0.98; P = .032). CONCLUSIONS: We
      found a significant association between very low magnesium intake and depression,
      especially in younger adults. The finding of the potential protective effect of
      low magnesium intake in older adults is surprising and warrants further
      investigation.

PMID- 25748768
TI  - Family physicians' scope of practice and American Board of Family Medicine
      recertification examination performance.
AB  - PURPOSE: Previous research indicated that rural family physicians were more
      likely to pass the American Board of Family Medicine (ABFM) Maintenance of
      Certification for Family Physicians (MC-FP) examination. One possible explanation
      is that rural family physicians may have a broader scope of practice. METHOD:
      This was a cross-sectional study of family physicians taking the ABFM MC-FP
      examination in 2013. Examination results were linked with the Scope of Practice
      for Primary Care (SP4PC) scale. Linear and logistic regression models, with and
      without SP4PC score, determined associations between scope of practice and
      examination results. RESULTS: Among 10,978 examinees, rural physicians had a
      higher passing rate (90.7% vs 86.8%, P < .05) and higher SP4PC score (16.1 vs
      14.3 P < .05) compared with urban physicians. Regression models without SP4PC
      score confirmed that urban physicians were less likely to pass (OR = 0.73; 95%
      CI, 0.62-0.87) and scored lower, -15.6 points, compared with rural physicians.
      Including SP4PC score completely attenuated the relationship between practice
      location and passing (OR = 0.86; 95% CI, 0.73-1.02) and decreased the
      relationship between score and practice location (-5.8 points). Each point
      increase on the SP4PC score was associated with 9% higher odds of passing (OR =
      1.09; 95% CI, 1.07-1.11) and 4.9 more points. CONCLUSION: A broader scope of
      practice rather than rural or urban practice location, was associated with
      increased likelihood of passing the MC-FP examination. If higher board scores are
      associated with providing higher quality of care, then maintaining a broad scope
      of practice may enable the delivery of higher quality primary care.

PMID- 25748767
TI  - Feasibility of portable sleep monitors to detect obstructive sleep apnea (OSA) in
      a vulnerable urban population.
AB  - PURPOSE: Portable sleep monitors may offer a convenient method to expand
      detection of obstructive sleep apnea (OSA), yet few studies have evaluated this
      technology in vulnerable populations. We therefore aimed to assess the
      feasibility and acceptability of portable sleep monitors for detection of OSA in
      a prediabetic, urban minority population. METHODS: We recruited a convenience
      sample of participants at their 12-month follow-up for a community-partnered,
      peer-led lifestyle intervention aimed to prevent diabetes in prediabetic and
      overweight patients in this prospective mixed-methods pilot study. All
      participants wore portable sleep monitors overnight at home. We qualitatively
      explored perceptions about OSA and portable monitors in a subset of participants.
      RESULTS: We tested 72 people, predominantly non-White, female, Spanish speaking,
      uninsured, and of low income. Use of portable sleep monitors was feasible: 100%
      of the monitors were returned and all participants received results. We detected
      OSA in 49% (defined as an Apnea-Hypopnea Index [AHI] >5) and moderate-severe OSA
      in 14% (AHI >15) requiring treatment in 14%. In 21 qualitative interviews,
      participants supported increased use of portable sleep monitors in their
      community, were appropriately concerned that OSA could cause progression to
      diabetes, and thought weight loss could prevent or improve OSA. CONCLUSIONS:
      Portable sleep monitors may represent a feasible method for detecting OSA in high
      risk urban minority populations.

PMID- 25748769
TI  - Inadequate reimbursement for care management to primary care offices.
AB  - BACKGROUND: Care management in primary care can be effective in helping patients
      with chronic disease improve their health; however, primary care practices are
      often challenged to identify revenue to pay for it. This study explored the
      impact of direct reimbursement on the provision of care management in a primary
      care physician organization. METHODS: Using data on expenses and health plan
      reimbursement during the initial 16 months of care management implementation at 5
      practices, we calculated the percentage of related costs that were covered by
      payments. Qualitative data from interviews with practice members were used to
      identify their perceived barriers to care management reimbursement and the impact
      of current reimbursement strategies on service delivery. RESULTS: Direct
      reimbursement for care management covered only 21% of the costs. Reimbursement
      varied by care manager background, patient diagnoses, insurer, and indication for
      the visit. Barriers to gaining reimbursement included patient resistance to
      copay, clinician hesitation to bill for care management visits (for fear the
      patient may receive a bill), differential reimbursement policies of insurers, and
      general lack of reimbursement for care management in many cases. Although
      practice-level quality improvement incentives were an alternative means of
      supporting care management, because these incentives were not directly tied to
      the service of care management, they were used for other activities ultimately
      supporting patient care. CONCLUSIONS: This study highlights the need for
      sufficient reimbursement to initiate and maintain care management for patients in
      primary care as proposed for service reforms under the Affordable Care Act.

PMID- 25748770
TI  - Using a lay cancer screening navigator to increase colorectal cancer screening
      rates.
AB  - INTRODUCTION: Preventive care is often not performed during the ambulatory office
      visit due to the acute nature of the visit. One possible strategy is the use of a
      lay cancer screening navigator using the lay health worker model. METHODS: A
      training program for the lay cancer screening navigator and a patient registry
      for colorectal cancer screening was developed. The RE-AIM framework was used to
      evaluate the intervention. Descriptive statistics were generated for patient
      demographics. RESULTS: Reach: The lay cancer screening navigator contacted 91.9%
      of eligible patients. Effectiveness: At baseline, 28.6% of patients were current
      on their colorectal cancer screening, 40.5% at 6 months, and 42.2% at 12 months.
      Adoption: Patients contacted all reported being receptive to the intervention.
      IMPLEMENTATION: Of the 368 fecal immunochemical test kits mailed, 151 were
      returned (41.0%), and 26 (17.2%) were positive. Maintenance: The percentage of
      patients who were current between 6 months and at 12 months were not
      significantly different. DISCUSSION: This study demonstrates that the use of a
      lay cancer screening navigator to increase the rate of colorectal cancer
      screening is a viable strategy.

PMID- 25748771
TI  - Diagnosis and management of acute coronary syndrome: an evidence-based update.
AB  - Acute coronary syndrome (ACS) describes the range of myocardial ischemic states
      that includes unstable angina, non-ST elevated myocardial infarction (MI), or ST
      elevated MI. ACS is associated with substantial morbidity and mortality and
      places a large financial burden on the health care system. The diagnosis of ACS
      begins with a thorough clinical assessment of a patient's presenting symptoms,
      electrocardiogram, and cardiac troponin levels as well as a review of past
      medical history. Early risk stratification can assist clinicians in determining
      whether an early invasive management strategy or an initial conservative strategy
      should be pursued and can help determine appropriate pharmacologic therapies. Key
      components in the management of ACS include coronary revascularization when
      indicated; prompt initiation of dual antiplatelet therapy and anticoagulation;
      and consideration of adjuvant agents including beta blockers, inhibitors of the
      renin angiotensin system, and HmG-coenzyme A reductase inhibitors. It is
      essential for clinicians to take an individualized approach to treatment and
      consider long-term safety and efficacy when managing patients with a history of
      ACS after hospital discharge. 

PMID- 25748772
TI  - Performance on the Maintenance of Certification for Family Physicians (MC-FP)
      examination: comparison of initial certfiers with experienced physicians.

PMID- 25748773
TI  - An appetite for connection.

PMID- 25748774
TI  - Assembling the Streptococcus thermophilus clustered regularly interspaced short
      palindromic repeats (CRISPR) array for multiplex DNA targeting.
AB  - In addition to the advantages of scalable, affordable, and easy to engineer, the
      clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR
      associated protein (Cas) technology is superior for multiplex targeting, which is
      laborious and inconvenient when achieved by cloning multiple gRNA expressing
      cassettes. Here, we report a simple CRISPR array assembling method which will
      facilitate multiplex targeting usage. First, the Streptococcus thermophilus
      CRISPR3/Cas locus was cloned. Second, different CRISPR arrays were assembled with
      different crRNA spacers. Transformation assays using different Escherichia coli
      strains demonstrated efficient plasmid DNA targeting, and we achieved targeting
      efficiency up to 95% with an assembled CRISPR array with three crRNA spacers. 

PMID- 25748775
TI  - The role of the thalamus in ADHD symptomatology and treatment.
AB  - Attention-deficit hyperactivity disorder (ADHD) is a chronic disorder with
      symptoms of inattention and impulsivity that partially remit with age. A review
      of longitudinal studies of children and adolescents with ADHD showed that the
      majority will have continued cognitive and functional impairments into adulthood.
      The thalamus likely plays a prominent role in ADHD symptomatology, based on
      evidence that the thalamus generates waking-state electroencephalography (EEG)
      rhythms along with extensive thalamic neural circuitry connections with cortical
      and subcortical areas. Research demonstrates a specific abnormality in the
      thalamic pulvinar nucleus in ADHD populations. The thalamus can also play a role
      in ADHD treatment, based on solid evidence that both animals and humans can learn
      to self-regulate EEG oscillations. Given the underarousal and sleep disturbance
      commonly seen in ADHD, along with data that indicate an increased dosage of ADHD
      medication may improve behavioral control at a cost of lowered cognitive
      functioning, further investigation of the role for self-regulation through EEG
      training is warranted. 

PMID- 25748776
TI  - In vitro scleral lutein distribution by cyclodextrin containing nanoemulsions.
AB  - Lutein is a macular pigment that contributes to maintaining eye health. The
      development of lutein-laden nanocarriers for ocular delivery would have the
      advantages of user friendliness and cost-effectiveness. Nano-scaled vehicles such
      as cyclodextrin (CD) and nanoemulsion could overcome the barriers caused by the
      scleral structure. This study focused on the development of hybrid nanocarriers
      containing nanoemulsion and CD for scleral lutein accumulation. In the presence
      of the nanoemulsion, CD forms such as betaCD and hydroxyethyl (HE) betaCD
      increased the partition of lutein into the porcine sclera. A combination of
      nanoemulsion and 2% HEbetaCD enhanced lutein accumulation to 119+/-6 ug g(-1) h(
      1), which was 9.2-fold higher than that with lutein suspension alone. We explored
      the dose effect of CD in nanoemulsion on scleral lutein and found that the
      scleral accumulation of lutein was enhanced by increasing the CD content. The
      novel nanoemulsion had 95% drug-loading efficiency and low cytotoxicity in
      retinal cells. The CD-modified nanoemulsion not only improved the stability and
      entrapment efficacy of lutein in the aqueous system but also enhanced scleral
      lutein accumulation. An increase in the partition coefficient of lutein in
      porcine sclera when using the CD-modified nanoemulsion was also confirmed.

PMID- 25748777
TI  - Synthesis and antimicrobial activity of amino linked heterocycles.
AB  - Amino-linked benzoxazolyl/benzothiazolyl/benzimidazolyl quinazolines were
      prepared and their antimicrobial activity studied. The nitro-substituted
      benzothiazolyl quinazoline (8f) may be a potential antibacterial agent against
      Staphylococcus aureus and nitro-substituted benzimidazolyl quinazoline (9f) may
      be a potential antifungal agent against Aspergillus niger. 

PMID- 25748778
TI  - Preparation of methacrylic acid copolymer S nano-fibers using a solvent-based
      electrospinning method and their application in pharmaceutical formulations.
AB  - In this study, we applied an electrospinning (ES) method, which is mainly
      employed in the textile industry, to the field of pharmaceuticals. We developed
      and modified an ES instrument and then utilized it to produce methacrylic acid
      copolymer S (MAC) nano-fibers to prepare tablets. By attaching a conductor rod
      made from stainless steel to the central part of the nano-fiber-collection plate
      of the ES apparatus, a MAC nano-fiber sheet could be produced effectively. In
      addition, we studied various operating conditions for this new ES method,
      including needle gauge, voltage between the electrodes, distance between the
      needle and nano-fiber-collection plate and the flow rate of MAC polymer solution,
      but these had no significant effect on the diameter of MAC nano-fibers. On the
      other hand, the viscosity (concentration) of MAC polymer solution and
      permittivity of solvent used to dilute MAC were closely related to the mean
      diameter of the nano-fibers. Tableting of MAC nano-fibers was performed using a
      tableting machine without lubricants, and addition of Tween 20 to the tablets
      enabled regulation of the release profile of a water-soluble drug. The modified
      ES method reported here is a useful technique for the controlled-release of drugs
      and has wide-ranging potential for pharmaceutical applications. 

PMID- 25748779
TI  - Characterization of a riboflavin non-aqueous nanosuspension prepared by bead
      milling for cutaneous application.
AB  - The purpose of this study was to characterize the non-aqueous nanosuspension of a
      hydrophilic drug prepared by bead milling for cutaneous application. Riboflavin
      was used as the model hydrophilic drug. The non-aqueous nanosuspensions were
      prepared by grinding riboflavin with zirconia beads using eight non-aqueous
      bases. The mean particle size of riboflavin in the suspensions ranged from 206 to
      469 nm, as determined by the dynamic light scattering method. Among the well
      dispersed samples, riboflavin nanosuspension prepared in oleic acid was selected
      for evaluation of the drug permeability through rat skin. The cumulative amount
      and permeation rate of riboflavin from the nanosuspension were approximately
      three times higher than those for unprocessed riboflavin in oleic acid.
      Fluorescence imaging of the riboflavin nanosuspension suggested improved
      penetration of riboflavin into the stratum corneum. Furthermore, the addition of
      polysorbate 65 or polyglyceryl-6 polyricinoleate to the nanosuspension prepared
      in oleic acid markedly improved the riboflavin dispersibility. These results show
      that the preparation of a nanosuspension in a non-aqueous base by bead milling is
      one of the simple methods to improve the skin permeability of hydrophilic drugs.

PMID- 25748780
TI  - Preparation and evaluation of highly drug-loaded fine globular granules using a
      multi-functional rotor processor.
AB  - The manufacture of highly drug-loaded fine globular granules eventually applied
      for orally disintegrating tablets has been investigated using a unique multi
      functional rotor processor with acetaminophen, which was used as a model drug
      substance. Experimental design and statistical analysis were used to evaluate
      potential relationships between three key operating parameters (i.e., the binder
      flow rate, atomization pressure and rotating speed) and a series of associated
      micromeritics (i.e., granule mean size, proportion of fine particles (106-212
      um), flowability, roundness and water content). The results of multiple linear
      regression analysis revealed several trends, including (1) the binder flow rate
      and atomization pressure had significant positive and negative effects on the
      granule mean size value, Carr's flowability index, granular roundness and water
      content, respectively; (2) the proportion of fine particles was positively
      affected by the product of interaction between the binder flow rate and
      atomization pressure; and (3) the granular roundness was negatively and
      positively affected by the product of interactions between the binder flow rate
      and the atomization pressure, and the binder flow rate and rotating speed,
      respectively. The results of this study led to the identification of optimal
      operating conditions for the preparation of granules, and could therefore be used
      to provide important information for the development of processes for the
      manufacture of highly drug-loaded fine globular granules.

PMID- 25748781
TI  - Design, synthesis and biological evaluation of novel quinazoline-based anti
      inflammatory agents acting as PDE4B inhibitors.
AB  - A novel series of quinzoline based compounds (IIIa-d, VIa-f, IXa-f) were
      designed, synthesized and screened for their inhibitory activity towards the
      PDE4B isoform. The in vivo anti-inflammatory effect of the titled compounds (IIIa
      d, VIa-f, IXa-f) as well as their effect on the level of tumor necrosis factor
      (TNF-alpha) were evaluated. Among all of the synthesized compounds, IXb, IXd and
      IXf, exhibited good inhibitory activity against PDE4B enzyme with inhibition
      percentages of 42, 62 and 68%, respectively. Most of the tested compounds showed
      potent anti-inflammatory activity compared to indomethacin with a marked decrease
      in TNF-alpha level. The ulcerogenic effect of the tested compounds was also
      examined. The gastric mucosa of the tested animals remained intact after oral
      administration of the hit compounds. Additionally, docking study was used to
      explore the possible binding mode of the active compounds on the PDE4B enzyme as
      well as to illustrate the selectivity of the active hits on the PDE4B isoform. 

PMID- 25748782
TI  - Cyclic sulfoxides-garlicnins K1, K2, and H1-extracted from Allium sativum.
AB  - Newly identified cyclic sulfoxides-garlicnins K1 (1), K2 (2), and H1 (3)-were
      isolated from the acetone extracts of the bulbs of garlic, Allium sativum.
      Garlicnin H1 (3) demonstrated potential to suppress tumor cell proliferation by
      regulating macrophage activation. The structures of garlicnins K1 and K2, 3,4
      dimethyl-5-allyl-tetrahydrothiophen-2-one-S-oxides, and the structure of
      garlicnin H1, 3-carboxy-3-hydroxy-4-methyl-5-allylsulfoxide-tetrahydrothiophen-2
      (ethane-1,2-diol)-S-oxide were characterized by spectroscopic analysis. 

PMID- 25748783
TI  - Reaction of acetaldehyde with 5-aminolevulinic acid via dihydropyrazine
      derivative.
AB  - When a solution of 5-aminolevulinic acid (ALA) was incubated with acetaldehyde at
      neutral pH, a product was generated. This product was identified as 3
      ethylpyrazine-2,5-dipropanoic acid (ETPY). ETPY was stable at neutral pH. It has
      been reported that ALA dimerizes at neutral pH generating 3,6-dihydropyrazine-2,5
      dipropanoic acid (DHPY), and subsequently resulting in pyrazine-2,5-dipropanoic
      acid (PY) by autoxidation. In the present reaction, DHPY generated from ALA
      reacted with acetaldehyde, resulting in ETPY. Preadministration of ALA 3 min
      prior to acetaldehyde injection supressed the toxicity of acetaldehyde in male
      mice. These results suggest that ALA may be useful as a scavenger for
      acetaldehyde.

PMID- 25748784
TI  - Pd-catalyzed P-arylation of triarylantimony dicarboxylates with dialkyl H
      phosphites without a base: synthesis of arylphosphonates.
AB  - The reaction of triarylantimony diacetates [Ar3Sb(OAc)2] with dialkyl H
      phosphites [H-PO(OR)2] in the presence of a Pd(PPh3)4 (5 mol%) catalyst led to
      the formation of arylphosphonates in moderate to excellent yield under base-free
      conditions. This reaction is the first example of carbon-phosphorus bond
      formation by using an organoantimony compound as a pseudo-halide.

PMID- 25748785
TI  - Synthesis of new nebularine analogues and their inhibitory activity against
      adenosine deaminase.
AB  - A number of new 2,6-disubstituted-1-deazanebularine analogues as well as two
      structurally related pyrazole-fused tricyclic nucleosides were prepared. Their
      synthesis was carried out by the conversion of 6-amino-2-picoline to a suitable 1
      deazapurine, followed by a Vorbruggen type glycosylation and subsequent
      elaboration of the condensed pyrazole ring. The synthesized nebularine analogues
      proved to be weak adenosine deaminase inhibitors. 

PMID- 25748786
TI  - Geochemical partitioning of Cu and Ni in mangrove sediments: relationships with
      their bioavailability.
AB  - Sequential extraction study was performed to determine the concentrations of non
      residual metal-complexes in the mangrove sediments from the Divar Island, (west
      coast of India). Accumulation of metal in the mangrove roots (from the same
      location) was determined and used as an indicator of bioavailability of metal. An
      attempt was made to establish a mechanistic linkage between the non-residual
      metal complexes and their bioavailability in the mangrove system. The non
      residual fractions of Cu and Ni were mainly associated with Fe/Mn oxyhydroxide
      and organic phases in the sediments. A part of these metal fractions were
      bioavailable in the system. These two phases were the major controlling factors
      for Ni speciation and their bioavailability in the studied sediments. However, Cu
      was found to interact more strongly with the organic phases than Ni in the
      mangrove sediments. Organic phases in the mangrove sediments acted as buffer to
      control the speciation and bioavailability of Cu in the system. 

PMID- 25748787
TI  - [Idiopathic overactive bladder: What to do in case of anticholinergic failure?].

PMID- 25748788
TI  - [Biochemical recurrence after curative treatment for localized prostate cancer:
      Performance of choline PET/CT in the assessment of local recurrence].
AB  - OBJECTIVE: To establish 18 fluorocholine-positron emission tomography/computed
      tomography (F-PET/CT) performances for the detection of local recurrence in a
      population of patients with biochemical failure after primary curative treatment
      for localized prostate carcinoma. MATERIAL AND METHOD: From February 2011 to
      February 2014, 55 patients underwent a F-PET/CT for biochemical relapse after
      primary radical therapy for prostate cancer localized or locally advanced.
      Primary therapies for prostate cancer were 19 radical prostatectomy, 18
      radiotherapy, 13 radiotherapy with hormonal treatment, 3 brachytherapy. The
      median age was 65 years (50-79). The initial staging was 17 T1, 23 T2 and 15 T3,
      52 were N0 and N1 3. The median PSA was 12 (3-127). The Gleason score was less
      than 7, equal to 7 and greater than 7 at 21, 25 and 9 patients respectively. The
      average time to recurrence was 69.5 months (8-147) with a median PSA of 2.9 ng/mL
      (0.48-41). RESULTS: In 42 cases, F-PET/CT showed uptake, suggesting a recurrence,
      metastatic (6), nodal (26) or local isolated (10). The focal uptake in PET
      commissioned in 5 cases prostate biopsy, confirming the histological recurrence
      of prostate cancer in 4 cases. Among the 10 patients with isolated local
      recurrence, 8 underwent salvage radiotherapy. Of the 13 cases where the (F
      PET/CT) showed no recurrence, 7 multiparametric MRI were performed. The MRI
      showed a local recurrence in 3 patients, the diagnoses were confirmed with
      prostate biopsy for two of them. CONCLUSION: In our study, for the patients with
      biochemical relapse of prostate adenocarcinoma localized or locally advanced, (F
      PET/CT) was able to detect local recurrence isolated in nearly half the cases but
      did not show sufficient sensitivity to exclude recurrence local if negative. It
      does not replace MRI or additional prostate biopsy.

PMID- 25748789
TI  - [Multicenter study of Advance (r) suburethral sling for treatment of
      postoperative urinary incontinence of male].
AB  - OBJECTIVES: To estimate in the medium term, the efficiency and morbidity of
      Advance((r)) for the treatment of postoperative urinary incontinence for male,
      and determine predictive preoperative factors of success or failure. MATERIAL AND
      METHODS: Retrospective multicentric clinical study of patients presenting a
      postoperative urinary incontinence and treated by Advance((r)) suburethral sling.
      The importance of the preoperative incontinence was classified in three groups:
      light (pad-test<50 g/day or 1 pad/day), moderated (pad-test between 50 and 100
      g/day or 2 or 3 pads/day), severe (pad-test>100 g/day or >3 pads/day). The
      functional results were classified in 4 categories: continence and improvement,
      defining the criterion of success and unchanged situation and deteriorated
      situation defining the criterion of failure. RESULTS: Sixty-six patients were
      included from 2008 till 2013. The radical prostatectomy was responsible in 85.5%
      of the cases. The incontinence was light, moderated and severe for respectively
      43.4%, 35.6% and 21% of the patients. After treatment, 39.4% of the patients were
      continent and 78.9% in situation of success. The rate of success decreased with
      the severity of the incontinence (respectively 94%, 74% and 56%). For 9 patients,
      implantation of artificial urinary sphincter was performed without operative
      difficulties. Complications were urine retention (n=4), hematoma (n=3) and
      scrotal pains persistent more than one postoperative month (n=11). CONCLUSION:
      Advance((r)) suburethral sling is a technique in which the efficiency decreases
      with the severity of the incontinence, but which does not seem to prevent from
      implanting artificial urinary sphincter. Its main problem is the apparition of
      scrotal pain.

PMID- 25748790
TI  - [Do postoperative drainage types modify outcomes after retrograde intrarenal
      surgery?].
AB  - INTRODUCTION: The aim of the current study was to evaluate if the postoperative
      drainage type modified the outcomes after retrograde flexible ureteroscopy (f
      URS) and intracorporeal lithotripsy f-URS for intrarenal stones. MATERIAL AND
      METHODS: We retrospectively analyzed 162 procedures of f-URS for intrarenal
      stones between January 2010 and January 2013 at a single institute. Independent
      sample t-tests and chi-square tests were used for comparisons of means and
      proportions between patients with ureteral stent or double pigtail stents.
      RESULTS: There were 86 males (52.8%) and 77 females (47.3%) with a mean age of
      52.8 +/- 17 years. Double pigtail stents and ureteral stents were used in 117
      (72.2%) and 45 (27.8%) cases, respectively. Cases with postoperative double
      pigtail stents had a longer operative time (96.2 +/- 35 min vs 81.2 +/- 5 min; P
      = 0.018) and were less often operated by an experienced surgeon (P = 0.001).
      Length of hospital staying (P = 0.804), postoperative complication (P = 0.148)
      and stone free status (P = 0.116) were not different between postoperative
      drainage by double pigtail and ureteral stents. CONCLUSION: Postoperative
      drainage by double pigtail stent was used more often by surgeons in the beginning
      of their RIRS experience and was associated with longer operation time.
      Nevertheless, the postoperative drainage type did not modify the outcomes
      regarding the postoperative complication rate, the length of hospital staying and
      the stones free rate.

PMID- 25748791
TI  - PRMT1-mediated arginine methylation controls ATXN2L localization.
AB  - Arginine methylation is a posttranslational modification that is of importance in
      diverse cellular processes. Recent proteomic mass spectrometry studies reported
      arginine methylation of ataxin-2-like (ATXN2L), the paralog of ataxin-2, a
      protein that is implicated in the neurodegenerative disorder spinocerebellar
      ataxia type 2. Here, we investigated the methylation state of ATXN2L and its
      significance for ATXN2L localization. We first confirmed that ATXN2L is
      asymmetrically dimethylated in vivo, and observed that the nuclear localization
      of ATXN2L is altered under methylation inhibition. We further discovered that
      ATXN2L associates with the protein arginine-N-methyltransferase 1 (PRMT1).
      Finally, we showed that neither mutation of the arginine-glycine-rich motifs of
      ATXN2L nor methylation inhibition alters ATXN2L localization to stress granules,
      suggesting that methylation of ATXN2L is probably not mandatory. 

PMID- 25748792
TI  - Extent of lymph node removal during esophageal cancer surgery and survival.
AB  - BACKGROUND: It is unclear how the extent of surgical lymph node clearance
      influences prognosis after surgery for esophageal cancer. METHODS: This
      nationwide, population-based cohort study included 1044 esophageal cancer
      patients who had undergone esophagectomy between 1987 and 2010 in Sweden, with
      follow-up until 2012. The independent role of lymph node removal in relation to
      survival was analyzed using Cox proportional hazards regression, providing hazard
      ratios (HRs) with 95% confidence intervals (CIs), adjusted for age, sex,
      comorbidity, tumor (T) stage, neo-adjuvant treatment, surgeon volume, and
      calendar period. Statistical tests were two-sided, except tests for trend.
      RESULTS: Analyzed as a linear variable, a higher number of lymph nodes removed
      did not influence the overall five-year mortality (adjusted HR = 1.00, 95% CI =
      0.99 to 1.01). Patients in the third (7-15 nodes) and fourth (16-114 nodes)
      quartiles of removed nodes did not demonstrate any decreased overall five-year
      mortality compared with those in the lowest two quartiles (<7 nodes) (HR = 1.13,
      95% CI = 0.95 to 1.35 and HR = 1.17, 95% CI = 0.94 to 1.46, respectively). In
      early T stages (Tis-T1) the hazard ratios indicated a worse survival with more
      lymphadenectomy using the median as cutoff (HR = 1.53, 95% CI = 1.13 to 2.06).
      Increased lymph node removal did not decrease mortality in any specific T stage.
      A greater number of metastatic nodes and a higher positive-to-negative node ratio
      were associated with strongly increased mortality. All results were similar when
      disease-specific mortality was analyzed. CONCLUSION: This population-based study
      indicates that more extensive lymph node clearance during surgery for esophageal
      cancer may not improve survival. These results challenge current clinical
      guidelines, and further research is needed to change clinical practice.

PMID- 25748793
TI  - The utility of case formulation in treatment decision making; the effect of
      experience and expertise.
AB  - OBJECTIVES: We examined whether case formulation guides the endorsement of
      appropriate treatment strategies. We also considered whether experience and
      training led to more effective treatment decisions. To examine these questions
      two related studies were conducted both of which used a novel paradigm using
      clinically relevant decision-making tasks with multiple sources of information.
      METHODS: Study one examined how clinicians utilised a pre-constructed CBT case
      formulation to plan treatment. Study two utilised a clinician-generated
      formulation to further examine the process of formulation development and the
      impact on treatment planning. Both studies considered the effect of therapist
      experience. RESULTS: Both studies indicated that clinicians used the case
      formulation to select treatment choices that were highly matched to the case as
      described in the vignette. However, differences between experts and novice
      clinicians were only demonstrated when clinicians developed their own
      formulations of case material. When they developed their own formulations the
      experts' formulations were more parsimonious, internally consistent, and
      contained fewer errors and the experts were less swayed by irrelevant treatment
      options. LIMITATIONS: The nature of the experimental task, involving ratings of
      suitability of possible treatment options suggested for the case, limits the
      interpretation that formulation directs the development or generation of the
      clinician's treatment plan. In study two the task may still have limited the
      capacity to demonstrate further differences between expert and novice therapists.
      CONCLUSIONS: Formulation helps guide certain aspects of effective treatment
      decision making. When asked to generate a formulation clinicians with greater
      experience and expertise do this more effectively.

PMID- 25748794
TI  - Prevention of healthcare-associated infections in neonates: room for improvement.
AB  - Infants in neonatal intensive care units (NICUs) are highly susceptible to
      infection due to the immaturity of their immune systems. Healthcare-associated
      infections (HCAIs) are associated with prolonged hospital stay, and represent a
      significant risk factor for neurological development problems and death.
      Improving HCAI control is a priority for NICUs. Many factors contribute to the
      occurrence of HCAIs in neonates such as poor hand hygiene, low nurse-infant
      ratios, environmental contamination and unnecessary use of antibiotics.
      Prevention is based on improving neonatal management, avoiding unnecessary use of
      central venous catheters, restricting use of antibiotics and H2 blockers, and
      introducing antifungal prophylaxis if necessary. Quality improvement
      interventions to reduce HCAIs in neonates seem to be the cornerstone of infection
      control. 

PMID- 25748795
TI  - Caveolin-1 phosphorylation regulates vascular endothelial insulin uptake and is
      impaired by insulin resistance in rats.
AB  - AIMS/HYPOTHESIS: As insulin entry into muscle interstitium is rate-limiting for
      its overall peripheral action, defining the route and regulation of its entry is
      critical. Caveolin-1 is required for caveola formation in vascular endothelial
      cells (ECs) and for EC insulin uptake. Whether this requirement reflects simply
      the need for caveola availability or involves a more active role for
      caveolae/caveolin-1 is not known. Here, we examined the role of insulin
      stimulated tyrosine 14 (Tyr(14))-caveolin-1 phosphorylation in mediating EC
      insulin uptake and the role of cellular Src-kinase (cSrc), TNF-alpha/IL-6 and
      high fat diet (HFD) in regulating this process. METHODS: Freshly isolated ECs
      from normal or HFD-fed rats and/or cultured ECs were treated with FITC-labelled
      or regular insulin with or without a Src or phosphotidylinositol-3-kinase
      inhibitor, TNF-alpha or IL-6, or transfecting FLAG-tagged wild-type (WT) or
      mutant (Y14F) caveolin-1. Tyr(14)-caveolin-1/Tyr(416) cSrc phosphorylation and
      FITC-insulin uptake were quantified by immunostaining and/or western blots.
      RESULTS: Insulin stimulated Tyr(14)-caveolin-1 phosphorylation during EC insulin
      uptake. Inhibiting cSrc, but not phosphotidylinositol-3-kinase, reduced insulin
      stimulated caveolin-1 phosphorylation. Furthermore, inhibiting cSrc reduced FITC
      insulin uptake by ~50%. Overexpression of caveolin-1Y14F inhibited, while
      overexpression of WT caveolin-1 increased, FITC-insulin uptake. Exposure of ECs
      to TNF-alpha or IL-6, or to 1-week HFD feeding eliminated insulin-stimulated
      caveolin-1 phosphorylation and inhibited FITC-insulin uptake to a similar extent.
      CONCLUSIONS/INTERPRETATION: Insulin stimulation of its own uptake requires
      caveolin-1 phosphorylation and Src-kinase activity. HFD in vivo and
      proinflammatory cytokines in vitro both inhibit this process.

PMID- 25748797
TI  - Qualitative studies of psychosocial interventions for dementia: a systematic
      review.
AB  - OBJECTIVES: Whilst a range of psychosocial interventions are used for people with
      dementia, there lacks evidence for the processes which underpin them. Systematic
      reviews focus on quantitative studies and there is a lack of qualitative reviews
      in the area. The review aimed to address this gap by exploring what existing
      qualitative studies reveal about the implementation, effects and processes of
      psychosocial interventions for dementia. METHOD: A systematic literature search
      was conducted, identifying 363 studies. Sixteen studies were found to meet the
      inclusion criteria and assessed for quality using pre-specified criteria.
      Thematic analysis was used to synthesise the findings. RESULTS: There were 10
      descriptive themes. Despite the diversity of the psychosocial interventions,
      there were common themes in relation to (1) contextual and individual factors
      affecting implementation (2) perceived impact of the interventions and (3) the
      processes active in achieving these effects. Study quality was adequate but
      variable. CONCLUSION: Common processes may underlie different psychosocial
      interventions for dementia. The synthesis of qualitative findings can offer
      insight into what makes interventions 'work' and factors which may facilitate or
      impede their use.

PMID- 25748796
TI  - Novel serine-based gemini surfactants as chemical permeation enhancers of local
      anesthetics: A comprehensive study on structure-activity relationships, molecular
      dynamics and dermal delivery.
AB  - This work aims at studying the efficacy of a series of novel biocompatible,
      serine-based surfactants as chemical permeation enhancers for two different local
      anesthetics, tetracaine and ropivacaine, combining an experimental and
      computational approach. The surfactants consist of gemini molecules structurally
      related, but with variations in headgroup charge (nonionic vs. cationic) and in
      the hydrocarbon chain lengths (main and spacer chains). In vitro permeation and
      molecular dynamics studies combined with cytotoxicity profiles were performed to
      investigate the permeation of both drugs, probe skin integrity, and rationalize
      the interactions at molecular level. Results show that these enhancers do not
      have significant deleterious effects on the skin structure and do not cause
      relevant changes on cell viability. Permeation across the skin is clearly
      improved using some of the selected serine-based gemini surfactants, namely the
      cationic ones with long alkyl chains and shorter spacer. This is noteworthy in
      the case of ropivacaine hydrochloride, which is not easily administered through
      the stratum corneum. Molecular dynamics results provide a mechanistic view of the
      surfactant action on lipid membranes that essentially corroborate the
      experimental observations. Overall, this study suggests the viability of these
      serine-based surfactants as suitable and promising delivery agents in
      pharmaceutical formulations. 

PMID- 25748798
TI  - Distribution of tissue characteristics of coronary plaques evaluated by
      integrated backscatter intravascular ultrasound: Differences between the inner
      and outer vessel curvature.
AB  - BACKGROUND: The purpose of the present study was to evaluate the tissue
      characteristics of plaques with moderate or mild stenosis in the inner and outer
      curvature of the left anterior descending artery (LAD) using integrated
      backscatter intravascular ultrasound. METHODS: We evaluated 66 plaques with
      moderate stenosis (plaque burden >50% but <=75%) and 49 plaques with mild
      stenosis (plaque burden >30% but <=50%) in 66 patients undergoing percutaneous
      intervention to the LAD. All plaques were >10mm away from any side branch or
      previously implanted stents. We divided vessel cross-sections into four quadrants
      (inner curvature, outer curvature, clockwise lateral side, and counterclockwise
      lateral side) using the septal branch as a landmark for the inner curvature. We
      averaged relative lipid area, relative fibrous area, and relative calcified area
      in minimal lumen area (MLA), three cross-sections proximal to the site of MLA,
      and three cross-sections distal to the site of MLA. RESULTS: In plaques with
      moderate stenosis, the relative lipid area in the inner curvature was
      significantly greater than in the outer curvature and lateral sides, whereas
      there was no significant difference in plaques with mild stenosis. CONCLUSION:
      The present study provides new findings that lipid pool is clustered in the inner
      curvature and fibrous tissue is clustered in the outer curvature of plaques with
      moderate stenosis in non-branching LAD lesions.

PMID- 25748799
TI  - Enterovirus replication: go with the (counter)flow.
AB  - All (+)RNA viruses replicate on distinct membranous domains; however, how they
      induce and maintain their unique lipid composition is largely unknown. Two recent
      studies reveal that enteroviruses harness the PI4P-cholestrol exchange cycle
      driven by OSBP1 protein and PI4 kinase(s), and that blocking the dynamic lipid
      flow inhibits virus replication. 

PMID- 25748800
TI  - Design and synthesis of nonionic copolypeptide hydrogels with reversible
      thermoresponsive and tunable physical properties.
AB  - Polypeptide-based formulations that undergo liquid to hydrogel transitions upon
      change in temperature have become desirable targets since they can be mixed with
      cells or injected into tissues as liquids, and subsequently transform into rigid
      scaffolds or depots. Such materials have been challenging to prepare using
      synthetic polypeptides, especially when reversible gelation and tunable physical
      properties are desired. Here, we designed and prepared new nonionic diblock
      copolypeptide hydrogels (DCH) containing hydrophilic poly(gamma-[2-(2
      methoxyethoxy)ethyl]-rac-glutamate) and hydrophobic poly(l-leucine) segments,
      named DCHEO, and also further incorporated copolypeptide domains into DCHEO to
      yield unprecedented thermoresponsive DCH, named DCHT. Although previous attempts
      to prepare nonionic hydrogels composed solely of synthetic polypeptides have been
      unsuccessful, our designs yielded materials with highly reversible thermal
      transitions and tunable properties. Nonionic, thermoresponsive DCHT were found to
      support the viability of suspended mesenchymal stem cells in vitro and were able
      to dissolve and provide prolonged release of both hydrophilic and hydrophobic
      molecules. The versatility of these materials was further demonstrated by the
      independent molecular tuning of DCHT liquid viscosity at room temperature and
      DCHT hydrogel stiffness at elevated temperature, as well as the DCHT liquid to
      hydrogel transition temperature itself. 

PMID- 25748801
TI  - Reduction of progesterone, estradiol and hCG secretion by perfluorooctane
      sulfonate via induction of apoptosis in human placental syncytiotrophoblasts.
AB  - INTRODUCTION: Perfluorooctane sulfonate (PFOS) is widely used as surfactants,
      lubricants, adhesives, fire retardants and propellants. Animal experiments have
      shown that PFOS can potentially influence reproductive function. The objective of
      the present study was to investigate the effects of PFOS on the endocrine
      function of human placental syncytiotrophoblasts. METHODS: Primary human
      placental cytotrophoblasts were isolated from term placenta. After
      syncytialization, the levels of aromatase and apoptosis-related proteins
      including caspase3, Bcl-2 and Bax were examined after treatment with PFOS from
      0.0001 MUM to 1 MUM or PFOS (0.1 MUM) in the presence and absence of apoptosis
      inhibitor Z-VAD-FMK (30 MUM) for 24 h. RESULTS: PFOS suppressed aromatase level
      and the secretion of estradiol, hCG and progesterone in a concentration-dependent
      manner from 0.0001 MUM to 1 MUM with a significant inhibition at 0.001 MUM and
      above in human placental syncytiotrophoblasts. Furthermore PFOS reduced cell
      viability and induced apoptosis in human placental syncytiotrophoblasts as
      revealed by increases of pro-apoptosis proteins such as Bax and cleaved-caspase3,
      and decreases of pro-caspase3 and anti-apoptosis protein Bcl-2. The apoptosis
      induced by PFOS was further illustrated by increased DNA fragmentation and
      nuclear condensation. Blocking apoptosis with pan-caspase inhibitor Z-VAD-FMK,
      the impairment of placental endocrine function by PFOS was restored. DISCUSSION:
      These results indicate that PFOS may disrupt the secretion of hCG, progesterone
      and estradiol by human placental syncytiotrophoblasts via induction of apoptosis.

PMID- 25748803
TI  - [Evolving treatment strategies for childhood brain tumours].

PMID- 25748802
TI  - Ephrin-B2 mediates trophoblast-dependent maternal spiral artery remodeling in
      first trimester.
AB  - INTRODUCTION: Maternal spiral artery remodeling after embryo implantation is a
      crucial process for successful pregnancy and rely on well-controlled trophoblast
      functions. Ephrin-B2 is found to be of great importance in various cell functions
      in both benign human tissue and tumors. However, its role in the regulation of
      trophoblast remains unknown. This study is conducted to investigate the role of
      ephrin-B2-induced trophoblast functions related to artery remodeling. METHODS:
      Trophoblast cell line HTR-8/SVneo was used to investigate the effects of ephrin
      B2 inhibition on cell proliferation, apoptosis, migration, invasion and tube
      formation. Placental-decidual co-culture (PDC) system was conducted to verify
      ephrin-B2-induced trophoblast functions ex vivo. Factors involving in artery
      remodeling process, such as matrix metalloproteinases (MMPs), placental growth
      factors (PlGF) and vascular endothelial growth factor (VEGF) were tested at
      transcriptional level. RESULTS: Inhibition of ephrin-B2 suppressed cell
      proliferation and induced cell apoptosis in HTR-8/SVneo cells. Down-regulation of
      ephrin-B2 impaired migration/invasion capabilities of HTR-8/SVneo cells and
      significantly decreased gene expression of MMPs. Also, a worse tube formation and
      a decrease in gene expression of PlGF was observed after down-regulation of
      ephrin-B2. However gene expression of VEGF-A did not show significantly
      statistical difference. These effects were further confirmed by PDC system
      showing an inadequate trophoblast invasion and spiral artery remodeling.
      DISCUSSION: Ephrin-B2 might be act as a positive regulator in maternal artery
      remodeling via both trophoblast invasion and endovascular formation.

PMID- 25748804
TI  - [Clinical features of intracerebral hemorrhage under antithrombotic therapy in
      the warfarin era].
AB  - We investigated the clinical characteristics and prognosis of intracerebral
      hemorrhage(ICH)under antithrombotic therapy. We retrospectively reviewed the
      medical records of 463 patients admitted to our hospital due to ICH during 3-year
      periiod between January 2010 and December 2012. The ICH patients were classified
      into 4 groups: patients with anticoagulant therapy(AC, n=36), antiplatelet
      therapy(AP, n=65), anticoagulant and antiplatelet therapies(AC+AP, n=18), and no
      antiplatelet or anticoagulant therapy(NT, n=344). There were no significant
      differences between the groups in terms of gender, hematoma location, and initial
      hematoma size. Age and previous history of ischemic cerebral disease or ischemic
      coronary disease were significantly higher in the AC, AP, and AC+AP groups than
      in the NT group. The number of patients who had received previous treatment for
      hypertension was higher in the AC, AP, and AC+AP groups, and systolic blood
      pressure at admission was lower in the AC and AC+AP groups than in the NT group.
      Hematoma enlargement occurred more frequently in the AC and AC+AP groups. The AC,
      AP and AC+AP groups showed worse prognosis and higher mortality than the NT
      group. Anticoagulant therapy can be a risk factor for hematoma enlargement, and
      anticoagulant and/or antiplatelet therapy can be a risk factor of poor outcome. 

PMID- 25748805
TI  - [Ruptured tiny middle cerebral artery aneurysm].
AB  - With new neuroimaging techniques, the detection rate of unruptured intracranial
      aneurysms has increased. While most detected aneurysms are small and left
      untreated because of the low risk of rupture, we still encounter many cases of
      small aneurysm rupture. Middle cerebral artery(MCA)aneurysms have lower risk of
      rupture compared to those in the anterior cerebral or internal carotid-posterior
      communicating arteries. Identification of small aneurysms with a high risk of
      rupture is important to improve management of these aneurysms. We report 10 cases
      of ruptured tiny(<3mm)MCA aneurysms. All patients underwent clipping and nine had
      good outcomes. One patient had poor outcome due to the worsening of chronic heart
      failure and kidney failure. A tiny aneurysm can rupture if the aneurysmal wall is
      fragile. Therefore, the fragility of the aneurysmal wall is an important
      predictive factor of rupture. Presently, however, it is difficult to determine
      when an operation for an unruptured tiny aneurysm is indicated; new neuroimaging
      techniques that detect the fragility of the aneurysmal wall are needed. 

PMID- 25748806
TI  - [Formation of a posterior fossa cyst after evacuation of chronic subdural
      hematomas from spinal surgery-induced liquorrhea: a case report].
AB  - Cerebrospinal fluid leaks following spinal surgery are relatively common
      complications. However, subdural hematomas are uncommon, and infratentorial
      subdural hemorrhages are extremely rare. An 80-year-old man who had a history of
      myocardial infarction and was being treated with antiplatelet drugs underwent
      excision of a nerve sheath tumor of the upper cervical spine. Postoperatively,
      the patient developed headache and experienced weakness in both lower extremities
      1 week after the surgery. In addition, he developed vomiting 2 weeks later.
      Magnetic resonance imaging revealed cerebrospinal fluid retention behind the
      upper cervical spine, subdural hematomas in the right supra- and infra-tentorial
      regions, and subdural hygromas in the left supra- and infra-tentorial regions.
      The chronic subdural hematoma in the right supratentorial region was evacuated
      through a burr hole. Marked cerebellar ptosis and hydrocephalus developed
      postoperatively. Thereafter, cerebellar symptoms appeared. The infratentorial
      subdural hematoma and hygromas diminished in size;however, a posterior fossa cyst
      was found behind the fourth ventricle. Ten weeks after the burr hole surgery, a
      ventriculoperitoneal(VP)shunt was installed to decrease the cerebrospinal fluid
      retention behind the fourth ventricle and to cure the liquorrhea by reducing
      cerebrospinal fluid flow into the subarachnoid space of the posterior cranial
      fossa and the spinal canal. The patient's postoperative course was satisfactory,
      and the liquorrhea disappeared. 

PMID- 25748807
TI  - [Metastatic brain tumor from esophageal carcinoma:a report of three cases].
AB  - A metastatic brain tumor originating from esophageal carcinoma is very rare,
      accounting for only about 2% of all intracranial metastatic tumors. We review
      three cases of metastatic brain tumor from esophageal carcinoma and present one
      interesting case. A 60-year-old man was referred to our hospital with aphasia, 3
      years after surgery for esophageal carcinoma. Magnetic resonance imaging
      demonstrated a 7-cm mass lesion with a cystic component in the left temporal
      lobe. Tumor resection was performed and an Ommaya reservoir system was placed.
      Histological analysis indicated squamous cell carcinoma, and metastatic brain
      tumor from esophageal carcinoma was diagnosed. After surgery, the cystic
      component was collapsed by drainage through the Ommaya reservoir, and cyberknife
      therapy was performed as an adjunctive therapy. Regrowth of the cystic component
      and exacerbation of cognitive dysfunction were identified 2 months later, so
      aspiration of cyst fluid through the Ommaya reservoir was continued. However, the
      cystic component regrew 5 months after the operation, and the patient died 1
      month later. Metastatic brain tumors from primary esophageal carcinoma often have
      a cystic component, which makes treatment difficult. Control of cyst growth by
      aspiration using the Ommaya reservoir is effective for improvement of functional
      prognosis in such patients. 

PMID- 25748808
TI  - [A case of akin moyamoya disease associated with type-I diabetes mellitus managed
      by extracranial-intracranial bypass].
AB  - Moyamoya disease is characterized by idiopathic steno-occlusion at the terminal
      portion of the internal carotid artery with concomitant abnormal vascular
      networks that can lead to transient ischemic attacks and hemorrhagic stroke with
      symptoms of headache, confusion, dizziness, ataxia, seizure, and cognitive and
      personality changes. Because these symptoms also occur in patients with type 1
      diabetes mellitus(T1DM), patients with both diseases might go unnoticed and
      without the less common diagnosis of akin moyamoya disease, accurate diagnosis
      and treatment could be delayed. Here, we report the case of a 32-year-old woman
      with past history of T1DM for 26 years presenting with right amaurosis, which was
      diagnosed as akin moyamoya disease even though she had suffered right incomplete
      hemiparesis 2 years ago. She underwent superficial temporal artery-middle
      cerebral artery anastomosis with pial synangiosis in the left hemisphere without
      complication. She had no cerebrovascular events postoperatively. Although akin
      moyamoya disease associated with T1DM is rare in Japan, we recommend that
      clinicians consider the coexistence of both diseases when evaluating patients
      with T1DM who have neurologic signs or symptoms and not overlook the possibility
      of cerebrovascular diseases, such as akin moyamoya disease. 

PMID- 25748809
TI  - [Multiple brain abscesses in the territory of the vertebral-basilar artery
      resulting from an infected aortic arch graft].
AB  - A 62-year-old man with high fever and in a state of disorientation was
      transferred to our hospital. One year before this transfer, he had undergone
      total arch replacement surgery for thoracic aortic dissection. On admission to
      our hospital, head MRI revealed multiple brain abscesses in the territory of the
      vertebral-basilar artery, and chest CT showed gas around the aortic graft, in
      particular, at the origin of the left subclavian artery. We diagnosed him with
      brain abscesses in the left vertebral-basilar artery resulting from an infected
      aortic graft. We immediately began administration of intravenous antibiotics.
      Although his blood, urine, and cerebrospinal fluid cultures were negative,
      fortunately, the brain abscesses and ectopic gas disappeared. Since reports of
      only antibiotic use for treating brain abscesses due to aortic graft infection
      are rare, the appropriate duration of antibiotic administration has not been
      established yet. Therefore, careful observation is required in this case. 

PMID- 25748810
TI  - [Supratentorial-infraoccipital approach supported by navigation and
      intraoperative magnetic resonance imaging for glioma located at the medial
      posterior temporal lobe: two case reports].
AB  - Resection of posteromedial temporal lobe lesions is challenging because surgical
      access through standard approaches requires excessive retraction or resection of
      temporal cortex. The utility of the supratentorial-infraoccipital approach for
      posteromedial temporal lobe lesions was first reported in 1995. Here, we report
      two cases of glioma located at the medial posterior temporal lobe. In both, total
      tumor removal was achieved by a supratentorial-infraoccipital approach using
      neuronavigation and intraoperative magnetic resonance imaging. Both patients
      presented with postoperative quadrantanopia because of optic radiation damage,
      but did not have worsening language, memory, or cognitive functions. 

PMID- 25748811
TI  - [A case of intraventricular isolated neurosarcoidosis diagnosed by
      neuroendoscopic biopsy].
AB  - A 76-year-old woman was admitted to our hospital because of dementia, nausea, and
      speech disturbances. Computed tomography(CT)of her brain showed hydrocephalus and
      an intra-ventricular mass with a left temporo-parieto-occipital low density area.
      She underwent emergency ventricular drainage. Thereafter, she was referred to our
      department: neurosurgery. Gadolinium-enhanced magnetic resonance imaging of the
      brain showed homonymous enhancement in the left lateral, third, and fourth
      ventricles. CT of her chest and abdomen showed no abnormal findings. Initially,
      we performed a neuro-endoscopic biopsy and made a histopathological diagnosis of
      noncaseating granuloma. However, because we did not detect pulmonary or ocular
      lesions, we eventually made a diagnosis of isolated neurosarcoidosis. She
      received a ventricular-peritoneal shunt and steroid pulse therapy, and recovered
      from all her symptoms. Neurosurgeons should be aware of the possibility of
      hydrocephalus mimicking an intraventricular tumor and caused by isolated
      neurosarcoidosis. In this article, we provide a case description and review of
      the literature. 

PMID- 25748812
TI  - [Complete remission of consciousness disturbances and spasticity due to a severe
      subarachnoid hemorrhage after intrathecal baclofen therapy: a case report].
AB  - Typically, intrathecal baclofen therapy(ITB)for spasticity is continuously
      required because the spasticity can recur if the ITB is stopped. Thus, an
      infusion pump for the ITB is permanently implanted. Some sporadic cases
      exhibiting remarkable improvements in their spasticity and consciousness
      disturbances have been reported after implanting the ITB pump. We experienced a
      rare case involving removal of the ITB pump after the spasticity resolved and the
      consciousness disturbances markedly improved. A 15-year-old girl developed a
      subarachnoid hemorrhage due to rupture of an aneurysm in the right anterior
      cerebral artery. Her initial Glasgow Coma Scale score was 4(E1V1M2). Trapping of
      the aneurysm and decompression craniotomy were performed. Subsequently, she
      underwent a tracheotomy, and a percutaneous gastrostomy(PEG)tube was implanted
      because of persistent consciousness disturbances. Cranioplasty and lumbar
      peritoneal shunt for normal pressure hydrocephalus were performed after 1 month.
      An ITB pump was implanted to improve the spasticity observed mainly in the lower
      extremities 61 days after hemorrhage onset. Right hemiparesis remained due to
      Kernohan's notch. After transfer to the rehabilitation hospital, her
      consciousness disturbances and spasticity remarkably improved(1.9 to 1.0 and 3.5
      to 1.0 on the Ashworth scale for the upper and lower extremities, respectively).
      The tracheostomy and PEG tubes were removed, and the baclofen dose was gradually
      reduced. She was completely off baclofen after 7 months, and she was discharged
      with a short leg brace and a cane for walking. The baclofen pump was then
      removed. In this case, temporary ITB improved the spasticity and consciousness
      disturbances. 

PMID- 25748813
TI  - [Required knowledge for stroke specialists (8) cerebral venous thrombosis].

PMID- 25748814
TI  - Induction of transient tenogenic phenotype of high-density cultured human dermal
      fibroblasts.
AB  - Previous study showed that high-density culture supported phenotype maintenance
      of in vitro expanded tenocytes. This study explored the possibility of inducing
      the tenogenic phenotype of dermal fibroblasts by high-density monolayer culture.
      Human fibroblasts were seeded either in high-density (2.5 * 10(6) per 10 cm dish)
      or at low-density (0.36 * 10(6) per 10 cm dish). A preliminary tenogenic
      phenotype was observed in high-density cultured cells after one passage with
      significantly enhanced tenogenic gene expression. With continued cultivation to
      passage 3, scleraxis (SCX), tenomodulin (TNMD), collagen I, III, VI, decorin and
      tenascin-c were all significantly upregulated in high-density cultured dermal
      fibroblasts as opposed to low-density cells. High-density culture also led to
      relatively elongated cell shape, whereas cells appeared in spread shape in low
      density culture. In addition, cytochalasin D treatment disrupted the cellular
      cytoskeleton and resulted in inhibition of density-induced tenogenic gene
      expression. However, high-density cultured fibroblasts failed to induce other
      lineage differentiations (osteogenic, chondrogenic and adipogenic). It also
      failed to induce tenogenic phenotype in high-density cultured chondrocytes.
      Mechanism studies revealed enhanced gene expression of growth and differentiation
      factors (GDF) 5, 6, 7 and 8 and transforming growth factor-beta (TGF-beta)1 in
      the high-density group and enhanced protein production of both GDF8 and TGF
      beta1. Moreover, BMP/GDF signaling inhibitor (LDN193189) and TGF-beta signaling
      inhibitor (LY2109761) could both abrogate the density induced phenotype. In
      conclusion, high-density culture was able to induce transient tenogenic phenotype
      of dermal fibroblasts likely via cell morphology change and production of pro
      tenogenic factors. 

PMID- 25748815
TI  - 18F-fluoro-ethyl-tyrosine positron emission tomography for grading and estimation
      of prognosis in patients with intracranial gliomas.
AB  - INTRODUCTION: Histopathological examination is the standard for grading and
      determination of diagnosis in intrinsic brain tumors though the possibility of
      malignization and tumor heterogeneity always bears the possibility of tumor under
      grading or misjudgement regarding the estimation of prognosis. The aim of the
      present study was to evaluate the use of (18)F-FET-PET (FET-PET) for the grading
      and estimation of prognosis in newly diagnosed patients with intracranial gliomas
      in a clinical setting. METHODS: Patients who were treated for a newly diagnosed
      intracranial glioma between January 2007 and May 2012, and had a preoperative FET
      PET and MRI scan between were included. The ratio of counts in a tumor VOI
      (volume of interest) with maximum uptake to the respective counts in a background
      VOI was calculated to provide the tumor-to-normal (T/N) ratio. The clinical and
      histopathological data (tumor grading, pre- and postoperative neurological
      status, Karnofsky Performance Status Scale scores, and overall survival rates)
      were recorded. RESULTS: One hundred fifty-two patients (39 WHO II, 26 WHO III, 87
      WHO IV) were included. The median T/N ratio was 2.81 (1.1-8.1). The median T/N
      ratio of low-grade glioma patients was 1.65 (1.1-3.7), and 3.14 (1.61-8.1,
      p<0.001) in high-grade glioma patients. The median survival for patients with WHO
      III tumors was 22.8 months (95% CI: 15.87%-NA) and 13.23 months (95% CI: 10.83
      15.6.%) for patients with WHO IV tumors (p=0.0001). For T/N<=1.6, no deaths were
      recorded; for 1.6<T/N<=3, median survival was 25.6 months (95% CI: 16.5%-NA),
      while for T/N>3, median survival was 14.0 months (95% CI: 11.7-16.2%, p<0.001).
      The test of the maximally selected log-rank statistic resulted in a T/N ratio of
      1.88 as the cut-off value, with the greatest difference in overall survival
      between patients with longer and shorter survival. The ROC curve for
      differentiation of low- vs. high-grade tumors with regard to the T/N ratio showed
      an area under the curve (AUC) of 0.903. Regarding the prognostic validity for
      overall survival ROC-curves for 12-month, 24-month and 48-month survival display
      a higher validity for the WHO-classification than for the imaging modalities
      though with an AUC of 0.847 for the 48-month survival T/N ratio and MRI contrast
      enhancement have a high prognostic value as well. CONCLUSION: Our study suggests
      that FET-PET can predict prognosis and survival in patients harboring
      intracranial gliomas and serves as a valuable tool to supplement the established
      clinical and histopathological parameters.

PMID- 25748816
TI  - Is this really an emergency? Reducing potentially preventable emergency
      department visits among nursing home residents.

PMID- 25748817
TI  - Elderly nursing home resident with head drop.

PMID- 25748818
TI  - Azithromycin and Risk of Cardiovascular Death: A Meta-Analytic Review of
      Observational Studies.
AB  - Recent evidence, though conflicting, suggests an association between azithromycin
      use and cardiovascular death. We conducted a systematic review and meta-analysis
      to evaluate the effect of azithromycin on risk of death. Multiple databases were
      searched. Authors independently screened and extracted the data from studies.
      Primary outcome of interest was risk of death (cardiovascular and/or
      noncardiovascular). Subgroup analyses were conducted to explore the source of a
      possible heterogeneity. Random effects model meta-analysis and hazards ratio (HR)
      were used to pool the data and calculate the overall effect estimate,
      respectively. Eight hundred twenty-eight citations, identified with 5 cohort
      studies that involved 2,246,178 episodes of azithromycin use, met our inclusion
      criteria. Azithromycin use was not associated with higher risk of death from any
      cause, HR = 0.99 [confidence interval (CI), 0.82-1.19], I = 54%, or
      cardiovascular cause, HR = 1.15 (CI, 0.66-2.00), I = 64%, but there was a
      moderate degree of heterogeneity. Subgroup analyses have shown no increased risk
      of death with azithromycin use in younger population with zero degree of
      heterogeneity, HR = 0.85 (CI, 0.66-1.09), I = 0%. However, current use of
      azithromycin (within 1-5 days of therapy) was associated with a higher risk of
      death among older population with mild degree of heterogeneity, HR = 1.64 (CI,
      1.23-2.19), I = 4%. In summary, azithromycin use was not associated with higher
      risk of death particularly in younger population. Nevertheless, older population
      might be at higher risk of death with current use of azithromycin, and an
      alternative therapy should probably be considered. 

PMID- 25748819
TI  - Reduced Fat Food Emulsions: Physicochemical, Sensory, and Biological Aspects.
AB  - Fat plays multiple important roles in imparting desirable sensory attributes to
      emulsion-based food products, such as sauces, dressings, soups, beverages, and
      desserts. However, there is concern that over consumption of fats leads to
      increased incidences of chronic diseases, such as obesity, coronary heart
      disease, and diabetes. Consequently, there is a need to develop reduced fat
      products with desirable sensory profiles that match those of their full-fat
      counterparts. The successful design of high quality reduced-fat products requires
      an understanding of the many roles that fat plays in determining the sensory
      attributes of food emulsions, and of appropriate strategies to replace some or
      all of these attributes. This paper reviews our current understanding of the
      influence of fat on the physicochemical and physiological attributes of food
      emulsions, and highlights some of the main approaches that can be used to create
      high quality emulsion-based food products with reduced fat contents. 

PMID- 25748821
TI  - Photoswitchable organic field-effect transistors and memory elements comprising
      an interfacial photochromic layer.
AB  - Optical memory elements based on photoswitchable organic field-effect transistors
      have been designed by using an interfacial layer of photochromic spirooxazine
      molecules sandwiched between semiconductor and dielectric layers. Optical and
      electrical programming of the designed devices leads to multiple discrete states
      demonstrating drastically different electrical characteristics (VTH, IDS) and
      advanced stability. 

PMID- 25748820
TI  - A conserved domain in the scc3 subunit of cohesin mediates the interaction with
      both mcd1 and the cohesin loader complex.
AB  - The Structural Maintenance of Chromosome (SMC) complex, termed cohesin, is
      essential for sister chromatid cohesion. Cohesin is also important for chromosome
      condensation, DNA repair, and gene expression. Cohesin is comprised of Scc3,
      Mcd1, Smc1, and Smc3. Scc3 also binds Pds5 and Wpl1, cohesin-associated proteins
      that regulate cohesin function, and to the Scc2/4 cohesin loader. We mutagenized
      SCC3 to elucidate its role in cohesin function. A 5 amino acid insertion after
      Scc3 residue I358, or a missense mutation of residue D373 in the adjacent
      stromalin conservative domain (SCD) induce inviability and defects in both
      cohesion and cohesin binding to chromosomes. The I358 and D373 mutants abrogate
      Scc3 binding to Mcd1. These results define an Scc3 region extending from I358
      through the SCD required for binding Mcd1, cohesin localization to chromosomes
      and cohesion. Scc3 binding to the cohesin loader, Pds5 and Wpl1 are unaffected in
      I358 mutant and the loader still binds the cohesin core trimer (Mcd1, Smc1 and
      Smc3). Thus, Scc3 plays a critical role in cohesin binding to chromosomes and
      cohesion at a step distinct from loader binding to the cohesin trimer. We show
      that residues Y371 and K372 within the SCD are critical for viability and
      chromosome condensation but dispensable for cohesion. However, scc3 Y371A and
      scc3 K372A bind normally to Mcd1. These alleles also provide evidence that Scc3
      has distinct mechanisms of cohesin loading to different loci. The cohesion
      competence, condensation-incompetence of Y371 and K372 mutants suggests that
      cohesin has at least one activity required specifically for condensation. 

PMID- 25748822
TI  - The primary structure of COMT gene is not involved in the diet shift of the giant
      or the red pandas.

PMID- 25748824
TI  - Enantioselective synthesis of tunable chiral Clickphine P,N-ligands and their
      application in Ir-catalyzed asymmetric hydrogenation.
AB  - A small library of highly tunable chiral Clickphine P,N-ligands has been prepared
      in an enantioselective fashion by Cu(I)-catalyzed asymmetric propargylic
      amination using a single chiral complex and a subsequent in situ cycloaddition
      click reaction. The scope of the propargylic amination to yield optically active
      triazolyl amines is described. The amines are transformed in a one-pot procedure
      to the corresponding Ir-Clickphine complexes, which serve as catalysts for the
      asymmetric hydrogenation of di-, tri-, and tetrasubstituted unfunctionalized
      alkenes. Enantioselectivities of up to 90% ee were obtained in these
      hydrogenations, which are among the best reported in the case of the
      tetrasubstituted substrate 2-(4'-methoxyphenyl)-3-methylbut-2-ene (9) (87% ee).
      This is a demonstration of the effective use of the chiral pool, as from one
      chiral catalyst a library of chiral Ir complexes has been synthesized that can
      hydrogenate various alkenes with high selectivity. 

PMID- 25748823
TI  - Race and reproductive coercion: a qualitative assessment.
AB  - BACKGROUND: Unintended pregnancy is common and disproportionately occurs among
      low-income and African-American (AA) women. Male partners may influence women's
      risk of unintended pregnancy through reproductive coercion, although studies have
      not assessed whether racial differences in reproductive coercion impact AA
      women's disparate risk for unintended pregnancy. We sought to describe women's
      experiences with pregnancy-promoting behaviors by male partners and explore
      differences in such experiences by race. METHODS: Semistructured interviews were
      conducted with low-income, AA and White women aged 18 to 45 years recruited from
      reproductive health clinics in Western Pennsylvania to explore contextual factors
      that shape women's contraceptive behaviors. Narratives were analyzed using
      content analysis and the constant comparison method. FINDINGS: Among the 66
      participants (36 AA and 30 White), 25 (38%) described experiences with male
      partner reproductive coercion. Narratives provided accounts of contraceptive
      sabotage, verbal pressure to promote pregnancy and specific pregnancy outcomes,
      and potential motives behind these behaviors. AA women in the sample reported
      experiences of reproductive coercion more often than White women (53% and 20%,
      respectively). AA women were also more likely than White women to attribute a
      current or prior pregnancy to reproductive coercion. AA women identified
      relationship transiency and impending incarceration as potential motivations for
      men to secure a connection with a female partner via pregnancy. CONCLUSIONS: Our
      findings suggest that reproductive coercion may be a factor contributing to
      disparities in unintended pregnancy. More research, including population-level
      studies, is needed to determine the impact of reproductive coercion on unintended
      pregnancy and to understand the social and structural factors associated with
      pregnancy-promoting behaviors.

PMID- 25748825
TI  - A three-dimensional phase diagram of growth-induced surface instabilities.
AB  - A variety of fascinating morphological patterns arise on surfaces of growing,
      developing or aging tissues, organs and microorganism colonies. These patterns
      can be classified into creases, wrinkles, folds, period-doubles, ridges and
      delaminated-buckles according to their distinctive topographical characteristics.
      One universal mechanism for the pattern formation has been long believed to be
      the mismatch strains between biological layers with different expanding or
      shrinking rates, which induce mechanical instabilities. However, a general model
      that accounts for the formation and evolution of these various surface
      instability patterns still does not exist. Here, we take biological structures at
      their current states as thermodynamic systems, treat each instability pattern as
      a thermodynamic phase, and construct a unified phase diagram that can
      quantitatively predict various types of growth-induced surface instabilities. We
      further validate the phase diagram with our experiments on surface instabilities
      induced by mismatch strains as well as the reported data on growth-induced
      instabilities in various biological systems. The predicted wavelengths and
      amplitudes of various instability patterns match well with our experimental data.
      It is expected that the unified phase diagram will not only advance the
      understanding of biological morphogenesis, but also significantly facilitate the
      design of new materials and structures by rationally harnessing surface
      instabilities. 

PMID- 25748826
TI  - The impact of symbolic and non-symbolic quantity on spatial learning.
AB  - An implicit mapping of number to space via a "mental number line" occurs
      automatically in adulthood. Here, we systematically explore the influence of
      differing representations of quantity (no quantity, non-symbolic magnitudes, and
      symbolic numbers) and directional flow of stimuli (random flow, left-to-right, or
      right-to-left) on learning and attention via a match-to-sample working memory
      task. When recalling a cognitively demanding string of spatial locations,
      subjects performed best when information was presented right-to-left. When non
      symbolic or symbolic numerical arrays were embedded in these spatial locations,
      and mental number line congruency prompted, this effect was attenuated and in
      some cases reversed. In particular, low-performing female participants who viewed
      increasing non-symbolic number arrays paired with the spatial locations exhibited
      better recall for left-to-right directional flow information relative to right-to
      left, and better processing for the left side of space relative to the right side
      of space. The presence of symbolic number during spatial learning enhanced recall
      to a greater degree than non-symbolic number--especially for female participants,
      and especially when cognitive load is high--and this difference was independent
      of directional flow of information. We conclude that quantity representations
      have the potential to scaffold spatial memory, but this potential is subtle, and
      mediated by the nature of the quantity and the gender and performance level of
      the learner.

PMID- 25748827
TI  - Incretin-based drugs and risk of acute pancreatitis: A nested-case control study
      within a healthcare database.
AB  - To assess the association between use of incretin-based drugs for diabetes
      mellitus and the occurrence of acute pancreatitis. A population-based, nested
      case-control study was performed within a cohort of 166,591 patients from the
      Lombardy region (Italy) aged 40 years or older who were newly treated with oral
      antihyperglycaemic agents between 2004 and 2007. Cases were 666 patients who
      experienced acute pancreatitis from April 1, 2008 until December 31, 2012. For
      each case patient, up to 20 controls were randomly selected from the cohort and
      matched on gender, age at cohort entry, and date of index prescription.
      Conditional logistic regression was used to model the risk of acute pancreatitis
      associated with use of incretin-based drugs within 30 days before
      hospitalization, after adjustment for several risk factors, including the use of
      other antihyperglycaemic agents. Sensitivity analyses were performed in order to
      account for possible sources of systematic uncertainty. Use of incretin-based
      drugs within 30 days was reported by 17 (2.6%) cases of acute pancreatitis versus
      193 (1.5%) controls. The corresponding multivariate odds ratio was 1.75 (95%
      confidence interval, 1.02 to 2.99). Slightly lower and no significant excess
      risks were observed by shortening (15 days) and increasing (60 and 90 days) the
      time-window at risk. This study supports a possible increased risk of acute
      pancreatitis in relation to use of incretin-based drugs reported in a few
      previous studies. However, given the potential for bias and the inconsistency
      with other studies, additional investigations are needed to clarify the safety of
      incretin-based-drugs.

PMID- 25748828
TI  - A case of hypoglycemia due to illegitimate sexual enhancement medication.
AB  - Sexual enhancement medication presents a large market for counterfeit versions.
      We report here a case of hypoglycemia caused by an illicit sexual enhancement
      medication containing an extremely large amount of the sulfonylurea drug
      glibenclamide together with a moderate amount sildenafil citrate. 

PMID- 25748829
TI  - WITHDRAWN: Effects of motivational interviewing on lifestyle modification and
      diabetes prevention in adults with pre-diabetes.
AB  - This article has been withdrawn at the request of the 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- 25748830
TI  - The effect of an egg breakfast on satiety in children and adolescents: a
      randomized crossover trial.
AB  - OBJECTIVE: To evaluate the effects of an egg breakfast on lunchtime energy intake
      in children (age 4-6 years) and adolescents (age 14-17 years). METHODS: In 2
      randomized crossover trials, participants received either an egg breakfast or an
      isocaloric bagel breakfast. In both trials, subsequent lunchtime energy intake
      was the primary outcome. The trial with adolescents also measured each
      participant's serum ghrelin, serum peptide YY (PYY), and self-assessment of
      appetite rated using a visual analog scale. RESULTS: Lunchtime food intakes after
      egg and bagel breakfasts were not significantly different for either age group.
      Visual analog scale ratings of hunger and satiety were also not different between
      the 2 treatments in adolescents. Consumption of the egg breakfast led to a
      significant increase in serum PYY levels (p = 0.0001) in adolescents. However,
      increased levels of PYY were not correlated with reduced food intake. CONCLUSION:
      Short-term food intake in children and adolescents is not differentially altered
      by an egg breakfast compared to a bagel breakfast.

PMID- 25748831
TI  - Chronic oleoylethanolamide treatment improves spatial cognitive deficits through
      enhancing hippocampal neurogenesis after transient focal cerebral ischemia.
AB  - Oleoylethanolamide (OEA) has been shown to have neuroprotective effects after
      acute cerebral ischemic injury. The aim of this study was to investigate the
      effects of chronic OEA treatment on ischemia-induced spatial cognitive
      impairments, electrophysiology behavior and hippocampal neurogenesis. Daily
      treatments of 30 mg/kg OEA significantly ameliorated spatial cognitive deficits
      and attenuated the inhibition of long-term potentiation (LTP) in the middle
      cerebral artery occlusion (MCAO) rat model. Moreover, OEA administration improved
      cognitive function in a manner associated with enhanced neurogenesis in the
      hippocampus. Further study demonstrated that treatment with OEA markedly
      increased the expressions of brain-derived neurotrophic factor (BDNF) and
      peroxisome proliferator-activated receptors alpha (PPARalpha). Our data suggest
      that chronic OEA treatment can exert functional recovery of cognitive impairments
      and neuroprotective effects against cerebral ischemic insult in rats via
      triggering of neurogenesis in the hippocampus, which supports the therapeutic use
      of OEA for cerebral ischemia.

PMID- 25748832
TI  - A Scalable Web-Based Module for Improving Surgical and Medical Practitioner
      Knowledge and Attitudes about Palliative and End-of-Life Care.
AB  - BACKGROUND: We built a web-based, interactive, self-directed learning module
      about end-of-life care. OBJECTIVE: The study objective was to develop an online
      module about end-of-life care targeted at surgeons, and to assess the effect of
      the module on attitudes towards and knowledge about end-of-life care. METHODS:
      Informed by a panel of experts in supportive care and educational assessment, we
      developed an instrument that required approximately 15 minutes to complete. The
      module targets surgeons, but is applicable to other practitioners as well. We
      recruited general surgeons, surgical subspecialists, and medical practitioners
      and subspecialists from UCLA and the GLA-VA (N=114). We compared pre- and post
      intervention scores for attitude and knowledge, then used ANOVA to compare the
      pre- and postmodule means for each level of the covariate. We performed
      bivariable analyses to assess the association of subject characteristic and
      change in score over time. We ran separate analyses to assess baseline and change
      scores based on the covariates we had selected a priori. RESULTS: Subjects
      improved meaningfully in all five domains of attitude and in each of the six
      knowledge items. Individuals younger than 30 years of age had the greatest change
      in attitudes about addressing pain, addressing end-of-life goals, and being
      actively involved as death approached; they also had the most marked improvement
      in total knowledge score. Having a family member die of cancer within the last
      five years or a personal experience with palliative care or hospice were
      associated with higher change scores. CONCLUSIONS: A web-based education module
      improved surgical and medical provider attitudes and knowledge about end-of-life
      care.

PMID- 25748833
TI  - Matrix metalloproteinases regulate extracellular levels of SDF-1/CXCL12, IL-6 and
      VEGF in hydrogen peroxide-stimulated human periodontal ligament fibroblasts.
AB  - Periodontitis is a highly prevalent infectious disease characterized by the
      progressive inflammatory destruction of tooth-supporting structures, leading to
      tooth loss. The underling molecular mechanisms of the disease are incompletely
      understood, precluding the development of more efficient screening, diagnostic
      and therapeutic approaches. We investigated the interrelation of three known
      effector mechanisms of the cellular response to periodontal infection, namely
      reactive oxygen species (ROS), matrix metalloproteinases (MMPs) and cytokines in
      primary cell cultures of human periodontal ligament fibroblast (hPDLF). We
      demonstrated that ROS increase the activity/levels of gelatinolytic MMPs, and
      stimulate cytokine secretion in hPDLF. Additionally, we proved that MMPs
      possesses immune modulatory capacity, regulating the secreted levels of cytokines
      in ROS-stimulated hPDLF cultures. This evidence provides further insight in the
      molecular pathogenesis of periodontitis, contributing to the future development
      of more effective therapies.

PMID- 25748834
TI  - Osteoprotegerin concentrations in patients with suspected reversible myocardial
      ischemia: observations from the Akershus Cardiac Examination (ACE) 1 Study.
AB  - Increased circulating osteoprotegerin (OPG) levels have been associated with the
      prevalence and severity of coronary artery disease and the risk of cardiovascular
      death. OPG is a cytokine of the tumor necrosis factor receptor superfamily and is
      expressed in various cell types in the body, including osteoblasts, inflammatory
      cells, vascular smooth muscle cells/endothelial cells and cardiomyocytes. The
      main sources determining OPG levels in the circulation however, are not well
      understood, and whether reversible myocardial ischemia influences OPG levels are
      not known. Accordingly, OPG levels were measured in 198 patients referred for
      exercise stress testing and myocardial perfusion imaging (MPI). In addition OPG
      levels were measured in 8 healthy control subjects performing a maximal bicycle
      stress test. Plasma samples were collected before, immediately after, 1.5h and
      4.5h after exercise stress testing with MPI. OPG levels at baseline were not
      different in patient with reversible myocardial ischemia (n=19) and patients
      without reversible ischemia (n=179) (4.7 [3.6-5.5]pmol/L vs. 4.3 [3.4-5.2]pmol/L,
      p=0.21), and there was an increase in OPG levels immediately after exercise
      regardless of whether or not the patient had reversible ischemia on MPI (absolute
      increase: 0.2 [0-0.55]pmol/L vs. 0.3 [0-0.5]pmol/L, p=0.72). OPG levels also
      increased immediately after stress in the 8 control subjects (3.5 (3.2-3.8)pmol/L
      at baseline to 3.8 (3.5-4.7), p=0.008). In conclusion, OPG levels increase
      acutely during exercise stress testing, but this increase is likely caused by
      mechanisms other than myocardial ischemia.

PMID- 25748835
TI  - Involvement of IL-1 genes in the cellular responses to carbon nanotube exposure.
AB  - The interleukin-1 (IL-1) family has been implicated in cellular responses to
      nanoparticles including carbon nanotubes (CNTs). IL-1alpha and beta are key
      proinflammatory cytokines important in inflammatory and oxidative stress
      responses. The aim of this study was to characterize the role of IL-1 in cellular
      responses of CNTs in cells from IL-1alpha/beta wild type (IL1-WT) mice and cells
      with reduced inflammatory potential from IL-1alpha/beta deficient (IL1-KO) mice.
      Two multi-walled CNTs, CNT-1 containing long and thick fibers and CNT-2
      containing short and thin fibers, were compared to UICC crocidolite asbestos
      fibers. Upon CNT exposure toxicity and apoptosis were affected differently in IL1
      WT and IL1-KO cells. Upregulation of TNFalpha and IL-1alpha mRNA expression in
      IL1-WT cells was dependent on the type of CNT. On the contrary precursor IL
      1alpha protein was downregulated after 24h. The mitogen-activated protein kinase
      (MAPK) c-Jun N-terminal kinase (JNK) was activated in IL1-KO cells and regulated
      by CNTs, whereas no significant changes of extracellular regulated kinase (ERK)
      were observed when comparing IL1-WT and IL1-KO cells. In summary, the results
      presented here indicate that IL-1 contributes to the cellular and molecular
      effects of CNT exposure and that the type of CNT has an important effect on the
      cellular response.

PMID- 25748836
TI  - Knockdown of interleukin-1alpha does not attenuate LPS-induced production of
      interleukin-1beta in mouse macrophages.
AB  - IL-1alpha and IL-1beta are synthesized as 31kDa cell-associated precursors
      following TLR-4 stimulation, but their processing to the mature form and
      secretion require a second intracellular stimulus. The unique localization of the
      precursor of IL-1alpha (pro-IL-1alpha) to the nucleus suggested a role in
      transcriptional regulation of inflammatory cytokines. We explored the hypothesis
      that pro-IL-1alpha is involved in regulation of IL-1beta expression following TLR
      4 stimulation. IL-1beta mRNA and protein levels were specifically decreased in
      macrophages from IL-1alpha-deficient mice following TLR-1/2, TLR-4 or TLR-9
      stimulation, supporting the hypothesis. However, activation of the main upstream
      regulators of IL-1beta expression, IRF3, NFkB and p38/JNK, were not reduced in
      macrophages from IL-1alpha-deficient mice. In order to assess the specific role
      of IL-1alpha in macrophages, we generated mice with myeloid cell deficiency of IL
      1alpha (LyzMCre-loxp). Despite over 90% knockdown of IL-1alpha, TLR-4 stimulated
      macrophages from LyzMCre-loxp mice did not produce lower levels of IL-1beta
      compared to IL-1alpha-loxp-flanked mice. In order to overcome the possibility
      that effects are caused by the incomplete deficiency of IL-1alpha, we generated
      new whole-body IL-1alpha knockout mice (GeneralCre-IL-1alpha) and the findings
      were similar to myeloid cell-deficient IL-1alpha. Collectively, our findings do
      not support the previously suggested role of nuclear IL-1alpha in gene regulation
      of IL-1beta. Rather, they suggest that IL-1alpha acts mainly as an alarmin that
      is sequestered in the nucleus following stimulation with TLR-4.

PMID- 25748837
TI  - Topical application of substance P promotes wound healing in streptozotocin
      induced diabetic rats.
AB  - Substance P (SP) is known to stimulate angiogenesis, fibroblasts proliferation
      and expressions of cytokines and growth factors involved in wound healing.
      However, SP level reduces in dermis in diabetics and, hence, it was hypothesized
      that exogenously applied SP could be helpful in improving wound healing in
      diabetic rats. Excision skin wound was created on the back of diabetic rats and
      rats were divided into three groups i.e. (i) saline-, (ii) gel- and (iii) SP
      treated. Normal saline, pluronic gel and SP (10(-6)M) in gel were topically
      applied once daily for 19days. SP treatment significantly increased the wound
      closure, levels of interleukin-10, and expressions of vascular endothelial growth
      factor, transforming growth factor-beta1, heme oxygenase-1 and endothelial nitric
      oxide synthase, whereas it significantly decreased the expression of tumor
      necrosis factor-alpha, interleukin-1beta and matrix metalloproteinases-9 in the
      granulation/healing tissue. The inflammatory cells were present for long time in
      normal saline-treated group. Histological evaluation revealed better
      extracellular matrix formation with marked fibroblast proliferation and collagen
      deposition in SP-treated group. Early epithelial layer formation, increased
      microvessel density and greater growth associated protein-43 positive nerve
      fibers were also evidenced in SP-treated group. In conclusion, SP treatment
      markedly accelerated cutaneous wound healing in diabetic rats.

PMID- 25748838
TI  - Airway inflammation in children and adolescents with bronchiolitis obliterans.
AB  - BACKGROUND: Airway inflammation plays a major role in the progression of chronic
      lung diseases. The features of airway inflammation are not well defined among
      patients with cases of bronchiolitis obliterans (BO) that began in childhood.
      OBJECTIVES: To investigate the sputum cell and cytokine profiles of stable cases
      of BO regarding lung function and the involvement of small airway disease (SAD).
      METHODS: Twenty patients with BO (median age=14.5, range=7-23years) and 22
      healthy controls (median age=16.5years, range=7-24years) were investigated. Lung
      function parameters and bronchial reversibility testing as well as sputum cell
      and cytokine profiles (IL-1beta, IL-6, IL-8, TNF-alpha, IL-5, IFN-gamma, and
      NFkappaB regulation) were analysed using quantitative RT-PCR and cytometric bead
      assay (CBA) in induced sputum. RESULTS: Patients with BO had significantly lower
      lung function values, including FVC, forced expiratory volume (FEV1), the
      Tiffeneau index (FEV1/VC), and MEF25, but increased functional residual capacity
      (RV/TLC) values. Bronchial reversibility was found in five patients (25%).
      Moreover, airway inflammation (as indicated by total cells, neutrophils, IL
      1beta, IL-6, IL-8, TNF-alpha, and NFkappaB) was significantly increased among
      patients with BO compared with controls. CONCLUSIONS: BO is predominantly a
      neutrophilic disease of the small bronchioles featuring elevated levels of pro
      inflammatory cytokines leading to tissue remodelling and fibrosis of the small
      airways. Future therapies for patients with BO should more efficiently target the
      small airways.

PMID- 25748839
TI  - Angiopoietin-2 associations with the underlying infection and sepsis severity.
AB  - Angiopoietin-2 (Ang-2) is an important mediator in sepsis. We have previously
      shown that endotoxemia levels are related to the underlying infection and affect
      septic patients' outcome. Based on this background we now investigated if
      circulating Ang-2 (cAng-2) and monocyte Ang-2 expression in septic patients are
      associated with the underlying infection and organ failure. We measured cAng-2 in
      288 septic patients (121 with sepsis, 167 with severe sepsis/septic shock) at
      less than 24h post study inclusion (day 1) and on days 3 and 7. Peripheral blood
      mononuclear cells (PBMCs) were additionally isolated; Ang-2 gene expression was
      estimated by means of real-time PCR. Levels of cAng-2 were higher under severe
      sepsis and septic shock, as compared to uncomplicated sepsis; PBMC Ang-2 copies
      were higher in severe sepsis. On day 1, cAng-2 and Ang-2 gene copies were greater
      under severe sepsis/septic shock in sufferers from all types of infections with
      the exception of community-acquired pneumonia and ventilator-associated
      pneumonia. cAng-2 increased proportionally to the number of failing organs, and
      was higher under metabolic acidosis and acute coagulopathy as compared to no
      failing organ. On day 1, copies of Ang-2 were higher in survivors, whereas cAng-2
      was higher in non-survivors. In a large cohort of septic patients, cAng-2
      kinetics appears associated with the underlying infection and organ failure type.

PMID- 25748840
TI  - Effect of Astragalus polysaccharide and its sulfated derivative on growth
      performance and immune condition of lipopolysaccharide-treated broilers.
AB  - This study evaluates the immunomodulating activities of Astragalus polysaccharide
      (APS) and sulfated APS (SAPS) in LPS-infected broiler chicks. SAPS was derived
      using the classic chlorosulfonic acid-pyridine method. On day 16, the birds were
      injected intramuscularly with 0.5 mL of either saline, APS (4 or 8 mg/kg of body
      weight (BW), shorten as APS-4 or APS-8) or SAPS (4 or 8 mg/kg of BW, shorten as
      SAPS-4 or SAPS-8) once a day for three successive days. On days 19 and 20, the
      birds were intraperitoneally injected with 0.5 mL of LPS (1mg/kg of BW). Saline
      was used as blank control. Compared with the blank control, LPS-treated birds
      showed lower daily body weight gain (BWG), average daily feed intake (ADFI),
      villus height and intraepithelial lymphocytes (IEL) number in jejunum, and higher
      feed conversion ratio (FCR, feed:gain), spleen index, plasma NO concentration,
      blood heterophil:lymphocyte (H:L) ratio, and the production of NO in the blood T
      lymphocytes. Compared with the LPS group, birds in APS-4, SAPS-4 and SAPS-8
      groups showed decreased FCR (P<0.05). Moreover, SAPS increased BWG and jejunal
      villus height (P<0.05) at 8 mg/kg BW. Plasma NO concentration was lower in APS-8
      group than that in LPS group (P<0.05). Both APS-8 and SAPS-8 treatments elevated
      the number of jejunal IEL (P<0.05), and decreased blood H:L ratio (P<0.05),
      respectively. Administration of APS or SAPS did not affect the ADFI, immune organ
      index, crypt depth and mucosal thickness of the jejunum, and the number of goblet
      cell. Our findings suggested that APS and SAPS possessed dose-dependent growth
      promoting and immunomodulating effect, and was a potential development direction
      for immunomodulator under early LPS stimulation condition.

PMID- 25748841
TI  - Identification of essential tryptophan in amylomaltase from Corynebacterium
      glutamicum.
AB  - This work aims to identify essential tryptophan residue(s) of amylomaltase from
      Corynebacterium glutamicum (CgAM) through chemical modification and site-directed
      mutagenesis techniques. The recombinant enzyme expressed by Escherichia coli was
      purified and treated with N-bromosuccinimide (NBS), a modifying agent for
      tryptophan. A significant decrease in enzyme activity was observed indicating
      that tryptophan is important for catalysis. Inactivation kinetics with NBS
      resulted in pseudo first-order rate constant (kinact) of 2.31 min(-1). Substrate
      protection experiment confirmed the active site localization of the NBS-modified
      tryptophan residue(s) in CgAM. Site-directed mutagenesis was performed on W330,
      W425 and W673 to localize essential tryptophan residues. Substitution by alanine
      resulted in the loss of intra- and intermolecular transglucosylation activities
      for all mutated CgAMs. Analysis of circular dichroism spectra showed no change in
      the secondary structure of W425A but a significant change for W330A and W673A
      from that of the WT. From these results in combination with X-ray structural data
      and interpretation from the binding interactions in the active site region, W425
      was confirmed to be essential for catalytic activity of CgAM. The hydrophobicity
      of this tryptophan was thought to be critical for substrate binding and
      supporting catalytic action of the three carboxylate residues at the active site.

PMID- 25748842
TI  - pH-responsive release behavior and anti-bacterial activity of bacterial cellulose
      silver nanocomposites.
AB  - Bacterial cellulose (BC) has been extensively explored as some of the most
      promising biomaterials for biomedical applications due to their unique
      properties, such as high crystallinity, high mechanical strength, ultrafine fiber
      network structure, good water holding capacity and biocompatibility. However, BC
      is lack of anti-bacterial activity which is the main issue to be solved. In the
      study, BC-Ag nanocomposites were prepared in situ by introducing silver
      nanoparticles (AgNPs) into BC acting as the templates. The BC and as-prepared BC
      Ag nanocomposites were characterized by several techniques including scanning
      electron microscope, Fourier transform infrared spectra, ultraviolet-visible
      absorption spectra, X-ray diffraction and thermogravimetric analyses. These
      results indicate AgNPs successfully impregnated into BC. The releases of Ag(+) at
      different pH values were studied, which showed pH-responsive release behaviors of
      BC-Ag nanocomposites. The anti-bacterial performances of BC-Ag nanocomposites
      were evaluated with Escherichia coli ATCC 25922, Staphylococcus aureus ATCC 6538,
      Bacillus subtilis ATCC 9372 and Candida albicans CMCC(F) 98001, which frequently
      causes medical associated infections. The experimental results showed BC-Ag
      nanocomposites have excellent anti-bacterial activities, thus confirming its
      utility as potential wound dressings. 

PMID- 25748843
TI  - Preparation and characterisation of gelatin-gum arabic aldehyde nanogels via
      inverse miniemulsion technique.
AB  - Gelatin-gum arabic aldehyde nanogels designed by a nanoreactor concept using
      inverse miniemulsion technique were reported. Stable separate miniemulsions were
      prepared from gelatin (Gel) and gum arabic aldehyde (GAA). These emulsions were
      intermixed under sonication to obtain cross-linked nanogels. During fusion, cross
      linking occurred between aldehyde groups of GAA and amino groups of gelatin. The
      concentration of the surfactant and weight fraction of water in the inverse
      miniemulsion was optimised so as to yield nanogels with controlled particle size.
      Properties of the nanogels were studied by FT-IR spectroscopy, particle size
      analysis and XRD. Surface morphology of the nanogels was established by Scanning
      Electron Microscopy (SEM). SEM and particle size analysis confirmed that nanogels
      possess spherical morphology with an average diameter of 151 +/- 6 nm. Hemolysis
      property of the nanogels was examined and the results indicated that the nanogels
      were hemocompatible. The in vitro cytotoxicity of the nanogels towards MCF-7
      cells was evaluated by MTT assay and the nanogels showed nontoxic behaviour
      towards the cells. All these studies confirm that these nanogels are potential
      candidates in applications such as drug and gene delivery.

PMID- 25748844
TI  - Effect of different drying methods on chemical composition and bioactivity of
      finger citron polysaccharides.
AB  - Traditionally, people like to take dried finger citron fruits (FC) as adjuvant
      herbal medicines to treat a diversity of chronic diseases like asthma,
      hypertension and respiratory tract infections. Many healing properties are
      attributed to FC polysaccharides (FCPs), one of the main active ingredients of
      FC. Three drying methods, freeze drying (FDM), hot air drying (HDM) and vacuum
      drying methods (VDM) were comparatively studied on the physicochemical and
      antioxidant properties of FCPs. The results showed these FCPs were similar in UV
      and FT-IR spectrum. However, they showed significant differences (p<0.05) in
      yields of crude polysaccharides and contents of protein and ash. Compared with
      VDM and HDM, FDM resulted in the properties of FCPs with lower molecular weight
      distribution, higher reducing power and scavenging abilities on DPPH, OH, and O2(
      ). Available data obtained in vitro models suggested that FDM was an appropriate
      and effective treatment for obtaining crude polysaccharides from FC fruits.
      Hence, drying methods used for preparation of FCPs can affect physicochemical and
      associated functional properties. 

PMID- 25748845
TI  - Characteristics of thermostable amylopullulanase of Geobacillus thermoleovorans
      and its truncated variants.
AB  - The far-UV CD spectroscopic analysis of the secondary structure in the
      temperature range between 30 and 90 degrees C revealed a compact and thermally
      stable structure of C-terminal truncated amylopullulanase of Geobacillus
      thermoleovorans NP33 (gt-apuDeltaC) with a higher melting temperature [58 degrees
      C] than G. thermoleovorans NP33 amylopullulanase (gt-apu) [50 degrees C] and the
      N-terminal truncated amylopullulanase from G. thermoleovorans NP33 (gt-apuDeltaN)
      [55 degrees C]. A significant decline in random coils in gt-apuDeltaC and gt
      apuDeltaN suggested an improvement in conformational stability, and thus, an
      enhancement in their thermal stability. The improvement in the thermostability of
      gt-apuDeltaC was corroborated by the thermodynamic parameters for enzyme
      inactivation. The Trp fluorescence emission (335 nm) and the acrylamide quenching
      constant (22.69 M(-1)) of gt-apuDeltaC indicated that the C-terminal truncation
      increases the conformational stability of the protein with the deeply buried
      tryptophan residues. The 8-Anilino Naphthalene Sulfonic acid (ANS) fluorescence
      experiments indicated the unfolding of gt-apu to expose its hydrophobic surface
      to a greater extent than the gt-apuDeltaC and gt-apuDeltaN.

PMID- 25748846
TI  - Effect of different chitosan derivatives on in vitro scratch wound assay: a
      comparative study.
AB  - Different strategies have been developed to make the wound-healing process faster
      and less painful. Recently, numerous studies demonstrated the ability of chitosan
      to accelerate wound healing. Aim of the present study has been to evaluate the
      effect of different chitosan derivatives to improve wound healing process.
      Quaternary ammonium-chitosan conjugates with low or high molecular weight (MW)
      and their thiolated derivatives effect were studied on human skin fibroblasts in
      terms of viability and migration (scratch wound assay). Results were compared
      both with basal medium (untreated cells) and with a positive control (chitosan
      chlorhydrate). After 24h both high and low MW chitosan derivatives were non-toxic
      up to 10 MUg/ml. The concentration of 10 MUg/ml was used for wound healing
      experiments. High-MW quaternary ammonium-chitosan conjugates bearing thiol groups
      on their chains were more effective in promoting cell migration than the non
      thiolated conjugates and the chitosan chlorhydrate. Moreover, they significantly
      improve wound healing process compared to untreated cells. According to the
      present in vitro preliminary results, high MW thiolated quaternary ammonium
      chitosan conjugates can be considered good candidates for the management of
      wounds.

PMID- 25748847
TI  - Mutations at calcium binding site III in cyclodextrin glycosyltransferase improve
      beta-cyclodextrin specificity.
AB  - Cyclodextrin glycosyltransferases (CGTases, EC 2.4.1.19) are industrially
      important enzymes that produce cyclodextrins from starch by intramolecular
      transglycosylation. In this study, the effects of amino acid residue at position
      315 in calcium binding site III (CaIII) on product specificity of CGTase were
      investigated by replacing Ala315 in the CGTase from Bacillus circulans STB01 with
      arginine, aspartic acid, threonine, leucine and valine. The cgt gene, which
      encodes this enzyme, was expressed in B. subtilis WB600 alongside site-directed
      mutants A315R, A315D, A315T, A315L and A315V. The results showed that CaIII plays
      an important role in cyclodextrin product specificity. Replacement of Ala315 by
      charged amino acid residues enhanced beta-cyclodextrin specificity, compared with
      the wild-type CGTase. Mutations A315R and A315D resulted in an approximately 10%
      increase in beta-cyclodextrin activity. Furthermore, under conditions resembling
      the industrial production processes, the mutants A315R and A315D displayed
      obvious increases in the production of beta-cyclodextrin, indicating they were
      much more suitable for the industrial production of beta-cyclodextrin than the
      wild-type enzyme. The enhancement of beta-cyclodextrin specificity for the
      mutants might be due to the stability of CaIII by charged amino acid
      substitutions. 

PMID- 25748848
TI  - Effect of incubation temperature on the self-assembly of regenerated silk
      fibroin: a study using AFM.
AB  - Understanding effect of temperature on the molecular self-assembly process will
      be helpful to unravel the structure-function relationship of biomolecule and to
      provide important information for the bottom-up approach to nanotechnology. In
      this work, the effect of incubation temperature on the secondary structures and
      morphological structures of regenerated silk fibroin (RSF) was systematically
      studied using atomic force microscopy and Fourier Transform infrared
      spectroscopy. The effect of incubation temperature on RSF self-assembly was
      dependent on RSF concentration. For the RSF solution with relatively low
      concentrations (15 MUg/mL and 60 MUg/mL), the increase of the incubation
      temperature mainly accelerated the formation and aggregation of antiparallel beta
      sheet protofibrils and decreased the formation of random coil
      protofilaments/globule-like molecules. For the RSF solution with relatively high
      concentrations (300 MUg/mL and 1.5mg/mL), the increase of the incubation
      temperature mainly accelerated the formation and aggregation of antiparallel beta
      sheet RSF features (protofibrils and globule-like features) and decreased the
      formation of random coil bead-like features. This work implies that the
      morphology and conformation of biomacromolecules could be tuned by controlling
      the incubation temperature. Further, it will be beneficial to basic understanding
      of the nanoscale structure formation in different silk-based biomaterials.

PMID- 25748849
TI  - Electrospun polyurethane-dextran nanofiber mats loaded with Estradiol for post
      menopausal wound dressing.
AB  - Post-menopausal wound care management is a substantial burden on health services,
      since there are an increased number of elderly populations linked with age
      related delayed wound healing. The controlled estrogen replacement can accelerate
      healing of acute cutaneous wounds, linked to its potent anti-inflammatory
      activity. The electrospinning technique can be used to introduce the desired
      therapeutic agents to the nanofiber matrix. So here we introduce a new material
      for wound tissue dressing, in which a polyurethane-dextran composite nanofibrous
      wound dressing material loaded with beta-estradiol was obtained through
      electrospinning. Dextran can promote neovascularization and skin regeneration in
      chronic wounds. This study involves the characterization of these nanofibers and
      analysis of cell growth and proliferation to determine the efficiency of tissue
      regeneration on these biocomposite polymer nanofibrous scaffolds and to study the
      possibility of using it as a potential wound dressing material in the in vivo
      models. 

PMID- 25748850
TI  - A conformation-based phage-display panning to screen neutralizing anti-VEGF VHHs
      with VEGFR2 mimicry behavior.
AB  - The potency of VEGF-based anti-angiogenic strategies in cancer therapy and the
      brilliant characteristics of VHHs motivated us to directly block VEGF binding to
      its receptor with neutralizing single domain antibodies, thereby fading away the
      VEGF signaling pathway. Considering with high resolution crystal structure of
      VEGF-RBD/VEGFR2 complex, we could adopt a combinatorial screening strategy:
      stringent panning and competition ELISA, to direct the panning procedure to
      dominantly screen the favorable binders that bind and block the key functional
      regions of VEGF. Based on competition assay, the majority of the screened clones
      (82%) showed the VEGFR2 mimicry behavior for binding to VEGF molecule. The phage
      pool gets enriched in favor of sequences that bind the receptor binding sites of
      VEGF. Different immunoassays and molecular docking simulation verified that all
      selected VHHs could bind and cover the receptor binding sites of VEGF.
      Consequently, some modifications in panning procedure with considering the
      structural features and detailed information of functional regions of a protein
      antigen, led us to successfully trap the high-affinity specific binders against
      its hot functional regions. Since the selected VHHs could cover the receptor
      binding site of VEGF and block VEGF binding to the receptor, they might be
      promising candidates for anti-angiogenic therapies. 

PMID- 25748851
TI  - Chitosan nanoparticle based delivery systems for sustainable agriculture.
AB  - Development of technologies that improve food productivity without any adverse
      impact on the ecosystem is the need of hour. In this context, development of
      controlled delivery systems for slow and sustained release of agrochemicals or
      genetic materials is crucial. Chitosan has emerged as a valuable carrier for
      controlled delivery of agrochemicals and genetic materials because of its proven
      biocompatibility, biodegradability, non-toxicity, and adsorption abilities. The
      major advantages of encapsulating agrochemicals and genetic material in a
      chitosan matrix include its ability to function as a protective reservoir for the
      active ingredients, protecting the ingredients from the surrounding environment
      while they are in the chitosan domain, and then controlling their release,
      allowing them to serve as efficient gene delivery systems for plant
      transformation or controlled release of pesticides. Despite the great progress in
      the use of chitosan in the area of medical and pharmaceutical sciences, there is
      still a wide knowledge gap regarding the potential application of chitosan for
      encapsulation of active ingredients in agriculture. Hence, the present article
      describes the current status of chitosan nanoparticle-based delivery systems in
      agriculture, and to highlight challenges that need to be overcome. 

PMID- 25748852
TI  - Improvement of interaction between PVA and chitosan via magnetite nanoparticles
      for drug delivery application.
AB  - Magnetite nanoparticles were synthesized by coprecipitation under ultrasonication
      followed by coating with chitosan. Polyvinyl alcohol (PVA) is then combined with
      the chitosan that coated the magnetite nanoparticles. The combination occurs by
      hydrogen binding and ionic cross-linking of the amino and hydroxyl groups of
      chitosan and PVA respectively. The magnetite nanoparticles have an average size
      of 10.62 nm that was confirmed by TEM. The VSM measurements showed that
      nanoparticles were superparamagnetic. The coatings on the core nanoparticles were
      estimated by AAS and the attachments of coating to the nanoparticles were
      confirmed by FT-IR analysis. Physicochemical properties of nanoparticles were
      measured by DLS and zeta potential. Naked magnetite, chitosan and PVA coating
      have zeta potential of +36.4, +48.1 and -12.5 mV respectively. The unspecific
      adsorption and interaction between nanoparticles and bovine serum albumin (BSA)
      were investigated systematically by UV-vis spectroscopy method. The nanoparticles
      that were modified by PVA present low protein adsorption, which makes them a
      practical choice for preventing opsonization in clinical application and drug
      delivery.

PMID- 25748853
TI  - Alternative nanostructures for thermophones.
AB  - Thermophones are highly promising for applications such as high-power SONAR
      arrays, flexible loudspeakers, and noise cancellation devices. So far,
      freestanding carbon nanotube aerogel sheets provide the most attractive
      performance as a thermoacoustic heat source. However, the limited accessibility
      of large-size freestanding carbon nanotube aerogel sheets and other even more
      exotic materials recently investigated hampers the field. We describe alternative
      materials for a thermoacoustic heat source with high-energy conversion
      efficiency, additional functionalities, environmentally friendly, and cost
      effective production technologies. We discuss the thermoacoustic performance of
      alternative nanostructured materials and compare their spectral and power
      dependencies of sound pressure in air. We demonstrate that the heat capacity of
      aerogel-like nanostructures can be extracted by a thorough analysis of the sound
      pressure spectra. The study presented here focuses on engineering thermal
      gradients in the vicinity of nanostructures and subsequent heat dissipation
      processes from the interior of encapsulated thermoacoustic projectors.
      Applications of thermoacoustic projectors for high-power SONAR arrays, sound
      cancellation, and optimal thermal design, regarding enhanced energy conversion
      efficiency, are discussed. 

PMID- 25748854
TI  - Interdisciplinary research teams.

PMID- 25748855
TI  - Perfectionism and stuttering: Findings of an online survey.
AB  - PURPOSE: Using a multi-dimensional measure of perfectionism: the Frost Multi
      dimensional Perfectionism Scale (FMPS: Frost, Marten, Lahart, & Rosenblate,
      1990), this study investigates: (a) whether adults who stutter (AWS) display more
      perfectionistic attitudes and beliefs than those who do not stutter, and (b)
      whether, in AWS, more perfectionistic attitudes and beliefs are associated with
      greater self-reported difficulty communicating verbally and speaking fluently.
      METHOD: In the first analysis, FMPS responses from 81 AWS and 81 matched,
      normally-fluent controls were analyzed using logistic regression to investigate
      the relative contributions of four FMPS perfectionism-subscale self-ratings to
      the likelihood of being in the AWS group. In the subsequent analyses, data from
      the 81 AWS were analyzed using linear multiple regression to determine which FMPS
      subscale self-ratings best predicted their Communication-Difficulty and Fluency
      Difficulty scores. RESULTS: Both the likelihood of being a member of the AWS
      group, and also the magnitude of the AWS group's Communication-Difficulty and
      Fluency-Difficulty scores, were positively part-correlated to respondents'
      Concern over Mistakes-Doubts about Actions (CMD) subscale self-ratings but
      negatively part-correlated to their Personal Standards (PS) subscale self
      ratings. CONCLUSIONS: The FMPS profiles of respondents who stutter suggest that,
      as a group, they are not abnormally perfectionistic overall, but may be (or
      perceive themselves to be) abnormally error-prone. Also, AWS who are more
      concerned about their errors and uncertain of their actions experience more
      difficulty communicating verbally and speaking fluently. EDUCATIONAL OBJECTIVES:
      After reading this article, participants will be able to: (a) describe the
      findings of previous research investigating the role of perfectionism in
      stuttering and psychopathologies; (b) discuss why a multidimensional assessment
      of perfectionism is important in relation to stuttering; (c) discuss ways in
      which data from perfectionism assessments can contribute to the planning of
      therapy for adults who stutter.

PMID- 25748856
TI  - Near-infrared supercontinuum laser beam source in the second and third near
      infrared optical windows used to image more deeply through thick tissue as
      compared with images from a lamp source.
AB  - With the use of longer near-infrared (NIR) wavelengths, image quality can be
      increased due to less scattering (described by the inverse wavelength power
      dependence 1/lambda(n) where n >= 1 ) and minimal absorption from water
      molecules. Longer NIR windows, known as the second (1100 nm to 1350 nm) and third
      (1600 to 1870 nm) NIR windows are utilized to penetrate more deeply into tissue
      media and produce high-quality images. An NIR supercontinuum (SC) laser light
      source, with wavelengths in the second and third NIR optical windows to image
      tissue provides ballistic imaging of tissue. The SC ballistic beam can penetrate
      depths of up to 10 mm through tissue.

PMID- 25748857
TI  - Photoacoustic lifetime imaging for direct in vivo tissue oxygen monitoring.
AB  - Measuring the partial pressure of oxygen (pO2) in tissue may provide physicians
      with essential information about the physiological state of tissue. However,
      currently available methods for measuring or imaging tissue pO2 have significant
      limitations, preventing them from being widely used in clinics. Recently, we have
      reported a direct and noninvasive in vivo imaging modality based on the
      photoacoustic lifetime which overcomes certain drawbacks of the existing methods.
      The technique maps the excited triplet state of oxygen-sensitive dye, thus
      reflecting the spatial and temporal distributions of tissue oxygen. Here, we
      present two studies which apply photoacoustic lifetime imaging (PALI) to monitor
      changes of tissue oxygen induced by external modulations. The first study
      modulates tissue oxygen by controlling the percentage of oxygen a normal mouse
      inhales. We demonstrate that PALI is able to reflect the change in oxygen level
      with respect to normal, oxygen-rich, and oxygen-poor breathing conditions. The
      second study involves an acute ischemia model using a thin thread tied around the
      hindlimb of a normal mouse to reduce the blood flow. PALI images were acquired
      before, during, and after the restriction. The drop of tissue pO2 and recovery
      from hypoxia due to reperfusion were tracked and observed by PALI.

PMID- 25748859
TI  - Proceedings of the international summit on emergency medicine and trauma 2014.

PMID- 25748858
TI  - The selective impairment of resting-state functional connectivity of the lateral
      subregion of the frontal pole in schizophrenia.
AB  - OBJECTIVE: Although extensive resting-state functional connectivity (rsFC)
      changes have been reported in schizophrenia, rsFC changes of the frontal pole
      (FP) remain unclear. The FP contains several subregions with different connection
      patterns; however, it is unknown whether the FP subregions are differentially
      affected in schizophrenia. To explore this possibility, we compared rsFC
      differences of the FP subregions between schizophrenia patients and healthy
      controls. METHOD: One hundred healthy controls and 91 patients with schizophrenia
      underwent resting-state functional MRI with a sensitivity-encoded spiral-in
      (SENSE-SPIRAL) imaging sequence to reduced susceptibility-induced signal loss and
      distortion. The FP was subdivided into the orbital (FPo), medial (FPm), and
      lateral (FPl) subregions. Mean fMRI time series were extracted for each FP
      subregion and entered into a seed-based rsFC analysis. RESULTS: The FP subregions
      exhibited differential rsFC patterns in both healthy controls and schizophrenia
      patients. Direct comparison between groups revealed reduced rsFCs between the
      bilateral FPl and several cognitive-related regions, including the dorsolateral
      prefrontal cortex, medial prefrontal cortex, anterior cingulate cortex, posterior
      cingulate cortex/precuneus, temporal cortex and inferior parietal lobule in
      schizophrenia. Although the FPl exhibited obvious atrophy, rsFC changes were
      unrelated to volumetric atrophy in the FPl, to duration of illness, and to
      antipsychotic medication dosage. No significant differences were observed in the
      rsFCs of other FP subregions. CONCLUSION: These findings suggest a selective (the
      lateral subregion) functional disconnection of the FP subregions in
      schizophrenia.

PMID- 25748860
TI  - Excess mortality during the first year after arterial trauma.
AB  - INTRODUCTION: Extant studies on arterial trauma originate from outside Denmark
      and their findings may therefore not apply to a Danish setting. The aim of the
      present study was to investigate the long-term mortality and clinical
      characteristics of patients with arterial trauma treated in Odense University
      Hospital (OUH). METHODS: This study was based on a historical cohort comprising
      all arterial traumas treated at OUH between 1990 and 2012. The Personal
      Identification Numbers were drawn and cross-referenced between The Danish
      Vascular Registry and the Accident Analysis Group. Mortality was compared with
      the expected mortality from the entire Danish population, matched to age, sex and
      date of trauma. RESULTS: A total of 231 patients were analysed. The median follow
      up period was 6.9 years (range: 0-22.47). Traffic was the most common cause of
      arterial trauma, violence the least common. Patients were mainly men (69%) with a
      median age of 32 years. Women had a median age of 46 years. The mortality rate
      ratios were as follows: overall in the first year 15.34 (95% confidence interval
      (CI): 10.34-21.93). Overall mortality rate ratios for year 1-5 was 1.66 (95% CI:
      0.82-2.98); but when stratified, the effect was only significant in the
      reconstructed subgroup (2.22 (95% CI: 1.01-4.24). CONCLUSION: Excess mortality
      was observed in patients with arterial traumas in the first year. However,
      patients receiving reconstructive arterial surgery after traumas had an excess
      mortality, even after adjustment for the effect of the first year. Whether the
      observed mortality is due to surgery itself, patients' risk behaviour or other
      factors remains unclear. Further national investigation is needed. FUNDING: not
      relevant. TRIAL REGISTRATION: not relevant. The study was approved by the Danish
      Data Protection Agency on 14 June 2013.

PMID- 25748861
TI  - Few Danish pregnant women follow guidelines on periconceptional use of folic
      acid.
AB  - INTRODUCTION: Approximately 60-70 pregnancies are affected by neural tube defects
      (NTD) in Denmark annually. Folic acid (FA) deficiency can cause NTD.
      Periconceptional FA supplementation reduces the risk of NTD by up to 70-80%.
      Danish women planning pregnancy are recommended 0.4 mg of FA daily from at least
      one month before planned conception and continuing throughout the first 12 weeks
      of pregnancy. The aim of the present study was to examine the knowledge about and
      use of FA supplementation among Danish pregnant women. METHODS: From 11 October
      2012 to 15 November 2012, all women attending for a routine nuchal translucency
      scan were given a questionnaire regarding their knowledge and use of FA
      supplementation during their current pregnancy. RESULTS: A total of 462 women
      answered the questionnaire. 95% had taken FA supplements at some point during
      their pregnancy, but only 10.4% as recommended. More than 80% stated knowledge
      about recommendations before the current pregnancy. Positive predictors of
      knowledge were: age > 30 years, multiparity, Danish origin and education > 3
      years. CONCLUSION: Despite national recommendations on periconceptional FA
      supplementation, our study showed that women do not follow these recommendations.
      Especially women with a low socio-economic status were likely to lack knowledge
      about FA supplementation in relation to pregnancy. There is a need for revision
      of the existing national recommendations and for other initiatives aiming to
      improve women's intake of FA, including FA fortification of flour and/or other
      food products. FUNDING: not relevant. TRIAL REGISTRATION: The study was approved
      by the Danish Data Protection Agency (No.: 01855 HVH-2012-044).

PMID- 25748862
TI  - Patients use normalisation techniques to cope with the quality-of-life effects of
      anal cancer.
AB  - INTRODUCTION: Anal cancer is a rare malignancy, but during the past three
      decades, its incidence has increased in both sexes. Approximately 90% of anal
      cancers are related to human papillomavirus infection. The primary treatment for
      anal cancer is radiotherapy or radio-chemotherapy. This quality of life (QoL)
      study aimed at obtaining in-depth knowledge about patients' experiences with anal
      cancer and its impact on their QoL. METHODS: A literature study identified topics
      for qualitative interviews with six anal cancer patients who had received
      oncological treatment and were without recurrent disease. The interviews were
      analysed using a medical anthroo-logical approach focusing on patients' health
      related phys-ical, psycho-sexual and social QoL. RESULTS: The participants
      suffered from common sequelae of anal cancer treatment, mainly ano-genital pain,
      reduced sphincter function and sexual dysfunction. The participants employed a
      number of "normalisation techniques", including dissociation from other cancer
      patients, delimitation of the cancer to a perceived external and peripheral body
      part and fast resumption of their usual activities. CONCLUSION: Anal sphincter
      dysfunction and sexual problems after radiotherapy for anal cancer may have a
      major impact on patients' QoL. By maintaining normalcy, patients tried to
      distance themselves from this tabooed cancer disease. FUNDING: not relevant.
      TRIAL REGISTRATION: not relevant, but approval was obtained from the Danish Data
      Protection Agency.

PMID- 25748863
TI  - Using a double-layered palmaris longus tendon for suspension of facial paralysis.
AB  - INTRODUCTION: Facial palsy is a debilitating condition entailing both cosmetic
      and functional limitations. Static suspension procedures can be performed when
      more advanced dynamic techniques are not indicated. Since 2006, we have used a
      double-layered palmaris longus tendon graft through an ovular skin excision in
      the nasolabial fold for access. The aim of this paper is to present our surgical
      technique and case series. METHODS: This study was a retrospective case series in
      a university hospital setting. All patients who had this procedure performed were
      included before August 2013. Data from electronic patient records were retrieved,
      patients were invited for a follow-up visit and results were measured using the
      Lip Reanimation Outcomes Questionnaire. Furthermore, standardised photographs
      were taken and evaluated by multiple surgeons. RESULTS: A total of 13 patients
      were included with a mean follow-up of 49 months (range: 3-89 months). 93% noted
      an improvement of their facial appearance at follow-up. Seven out of 11 patients
      with preoperative problems with speech noted an improvement at follow-up. Eight
      out of 12 patients with preoperative problems with oral competence noted an
      improvement at follow-up. Photographic evaluation revealed an acceptable symmetry
      at rest with an increasing asymmetry with increasing smile intensity. No post
      operative complications or donor site morbidity was noted in any of our patients.
      CONCLUSION: Our technique is easy to perform with no noteworthy complications,
      and it improves the quality of life of patients with facial palsy. It is an
      acceptable alternative when more advanced procedures are not indicated. FUNDING:
      not relevant. TRIAL REGISTRATION: not relevant.

PMID- 25748864
TI  - Effectiveness of anti-tumour necrosis factor-alpha therapy in Danish patients
      with inflammatory bowel diseases.
AB  - INTRODUCTION: The objective of this study was to evaluate the outcome of anti
      tumour necrosis factor-alpha (anti-TNF) treatment in a large cohort of patients
      with inflammatory bowel diseases (IBD), including Crohn's disease (CD) and
      ulcerative colitis (UC) in clinical practice and to establish a cohort for future
      studies of genetic markers associated with treatment response. METHODS: A
      national, clinically based cohort of previously naive anti-TNF treated patients
      from 18 medical departments was established. The patients were screened for
      tuberculosis prior to treatment initiation. By combining the unique personal
      identification number of Danish citizens (the CPR number) from blood samples with
      data from the National Patient Registry, patients with International
      Classification of Diseases, Version 10 (ICD-10) codes K50-K63 were identified.
      Treatment efficacy reflected the maximum response within 22 weeks. RESULTS: Among
      492 patients with CD and 267 patients with UC, 74%/13%/14% and 65%/12%/24% were
      responders, partial responders and non-responders to anti-TNF therapy,
      respectively. More patients with UC than with CD were non-responders (odds ratio
      (OR) = 1.96, 95% confidence interval (CI): 1.34-2.87, p = 0.001). Young age was
      associated with a beneficial response (p = 0.03), whereas smoking >= 10
      cigarettes/day was associated with non-response among patients with CD (OR =
      2.33, 95% CI: 1.13-4.81, p = 0.03). CONCLUSION: In this clinically based cohort
      of Danish patients with IBD treated with anti-TNF, high response rates were
      found. Heavy smoking was associated with non-response, whereas young age at
      treatment initiation was associated with a beneficial response among patients
      with CD. Thus, the results obtained in this cohort recruited from clinical
      practice were similar to those previously obtained in clinical trials. FUNDING:
      The work was funded by Health Research Fund of Central Denmark Region, Colitis
      Crohn Foreningen and the University of Aarhus (PhD grant). TRIAL REGISTRATION:
      Clinicaltrials NCT02322008.

PMID- 25748865
TI  - Hospital contacts after bite by the European adder (Vipera berus).
AB  - INTRODUCTION: Bites by the European adder, Vipera berus, may cause significant
      morbidity in bite victims, but this can be reduced through adequate treatment.
      Since the previous Danish study, a new treatment and a severity grading has been
      taken into use. The aims of this study were to review clinical cases after a bite
      from V. berus in The North Denmark Region and to evaluate the treatment given.
      METHODS: In the regional health-care database, we retrospectively identified all
      patients discharged with the International Classification of Diseases, 10th
      version (ICD-10) code "T 63.0 snake venom" in the 2007-2013 period. We reviewed
      patient records for patient demographics, clinical information and information
      about treatment. RESULTS: During the study period, 76 patients were discharged
      from a hospital after being bitten by V. berus in The North Denmark Region.
      Envenomation grade 2 or 3 was seen in 61% of victims, and 21% of these were
      treated with antivenom. T-wave inversion was seen in 9% of the 54 patients in
      whom an electrocardiography had been performed. The median duration of admittance
      was 24 hours (mean 48 hours), and risk factors for a prolonged stay at the
      hospital were grade 2 or 3 envenomation, leukocytosis and moderate/massive oedema
      at the time of admittance. CONCLUSION: Patients were admitted for a longer time
      than reported from a previous Danish study on adder bites, and many patients were
      possibly undertreated with regard to use of antivenom according to
      recommendations in recent guidelines. No adverse effects were noted due to
      administration of antivenom. T-wave inversion was observed more frequently than
      previously described. FUNDING: not relevant. TRIAL REGISTRATION: The study was
      recorded with The North Denmark Region in accordance with a directive from the
      Danish Data Protection Agency.

PMID- 25748866
TI  - Arthroscopic subacromial decompression results in normal shoulder function after
      two years in less than 50% of patients.
AB  - INTRODUCTION: The aim of this study was to evaluate the outcome two years after
      arthroscopic subacromial decompression using the Western Ontario Rotator-Cuff
      (WORC) index and a diagram-based questionnaire to self-assess active shoulder
      range of motion (ROM). METHODS: Outcomes in 80 patients with impingement of the
      shoulder undergoing arthroscopic subacromial decompression were prospectively
      assessed preoperatively, at three months and at two years post-operatively using
      the WORC index. All patients had received non-operative treatment for at least
      six months before undergoing surgery. Active range of motion was measured
      preoperatively by the examining physician and at two years by the patient him
      /herself using a diagram-based questionnaire to self-assess active shoulder ROM.
      A total of 75 patients (94%), of whom 31 were women, completed the study. The
      median age was 56 years. In all, 31 patients had additional resection of the
      acromioclavicular joint. RESULTS: WORC scores improved significantly from
      preoperatively (median: 1,392) to three months (median: 204) and two years post
      operatively (median: 243) (p < 0.001). A clinically significant decrease in the
      WORC index was observed in 83% of patients, but only 45% reported near normal or
      normal WORC scores, and 56% presented with a reduced active ROM at two years.
      CONCLUSION: Arthroscopic subacromial decompression -appears effective in
      alleviating symptoms in patients with subacromial impingement who are resistant
      to conservative treatment, but can only be expected to restore normal shoulder
      function as measured by the WORC in less than 50% of the cases. FUNDING: not
      relevant. TRIAL REGISTRATION: not relevant.

PMID- 25748867
TI  - Body mass index is not associated with reoperation rates in patients with a
      surgically treated perforated peptic ulcer.
AB  - INTRODUCTION: The aim of the present nationwide Danish cohort study was to
      examine the association between body mass index (BMI) and reoperation in patients
      who are sur-gically treated for perforated peptic ulcer (PPU). METHODS: This was
      a nationwide cohort study of all Danish patients who were surgically treated for
      benign gastric or duodenal PPU between 2011 and 2013. OUTCOME MEASURES:
      reoperation within 30 days of the primary surgical procedure and 90-day survival.
      The association between BMI and reoperation are presented as crude and adjusted
      odds ratios (OR) with 95% confidence intervals (CIs). RESULTS: A total of 726
      patients were included. The median age was 69.5 years (range: 18.2-101.7 years),
      51.4% were women (n = 373), 78.4% (n = 569) of the patients had at least one co
      existing disease, and 47.5% (n = 345) were categorised as American Society of
      Anesthesiologists (ASA) class >= 3. Re-operative surgery was done in 124 patients
      (17.1%). No statistically significant adjusted association between underweight,
      overweight or obesity and re-operation was found (adjusted OR (95% CI): 0.456
      (0.181-1.148), 1.468 (0.857-2.517), and 1.314 (0.663-2.601), respectively).
      Patients undergoing reoperative surgery had a statistically significantly lower
      crude 90-day survival than patients without need of reperative surgery; 63.9%
      (83/124) versus 75.9% (457/602), p = 0.037. CONCLUSION: In the present nationwide
      cohort study of PPU patients, no statistically significantly adjusted correlation
      between BMI and re-operation rates was found. Patients undergoing reoperative
      surgery had a decreased 90-day survival. FUNDING: not relevant. TRIAL
      REGISTRATION: not relevant.

PMID- 25748868
TI  - Legislation hampers medical research in acute situations.
AB  - INTRODUCTION: Informed consent in incapacitated adults is permitted in the form
      of proxy consent by both the patients' closest relative (next of kin, NOK) and
      general practitioner (GP). In research in acute situations not involving
      pharmaceuticals, Danish legislation allows for randomisation and subsequent proxy
      consent, as soon as possible. The aim of this study was to describe the delay
      associated with obtaining consent and to assess whether consent from NOK or
      GP/Danish Health and Medicines Authority is obtained with delays beyond the
      intervention. METHODS: In a prospective study, 171 comatose out-of-hospital
      cardiac arrest (OHCA) patients were randomised to targeted temperature
      management. Patients were randomised before NOK could be informed, and proxy
      consent was obtained as soon as possible. Written consent from NOK and GP were
      our study data. RESULTS: We obtained all legally required consent: 169 cases of
      consent were obtained from NOK, two patients gave consent before NOK, in no cases
      was consent denied by the proxy. Consent from NOK was obtained with a median
      delay of zero days (interquartile range (IQR): 0-1, max. 128 days). Delay from
      NOK consent to GP consent was a median of nine days (IQR: 6-23, max. 527 days).
      CONCLUSION: NOK fully accepted participation in a clinical trial after OHCA with
      short delays in consent. Consent from GPs was associated with long delays beyond
      the intervention, which make GPs less appropriate for proxy consent of
      incapacitated adults in acute situations. The Ethics Committees' approval of the
      trial justified by their competence and authority, combined with the NOK's
      insight into the patient's wishes may be a relevant and feasible alternative to
      the current consent procedure. FUNDING: This work was supported by the European
      Regional Development Fund through the Interreg IV A OKS programme (NYPS ID:
      167157) with regards to authors JHT, CH, NN and JK. TRIAL REGISTRATION: not
      relevant.

PMID- 25748869
TI  - Education, occupation and risk-taking behaviour among adults with attention
      deficit/hyperactivity disorder.
AB  - INTRODUCTION: No Danish studies examining functional impairments in a
      naturalistic sample of clinically referred adults with attention
      deficit/hyperactivity disorder (ADHD) are available. Our study aimed to examine
      educational and occupational outcomes and risk-taking behaviour in a Danish
      clinical sample of adults with ADHD. METHODS: Naturalistic, cross-sectional study
      of 155 ADHD adults consecutively referred to a Danish ADHD clinic from 2010 to
      2011. RESULTS: A total of 51% had primary/lower secondary school only as their
      highest education, and 65% were not self-supporting at the time of their
      assessment. Criminal behaviour was found in more than 50%, suspension of driving
      licence in 16% and risk-taking sexual behaviour in 37-51%. Co-morbidity did not
      significantly increase the odds for a low educational level or of risk-taking
      behaviours. Having a personality disorder (PD) increased occupational
      vulnerability. Male gender and ADHD-C (combined type) were significantly
      associated with criminality and suspension of driving licence. Patients with
      substance use disorders and PD had non-significantly increased odds for risk
      taking behaviours. CONCLUSION: Functional impairments were evident in this Danish
      sample of adults with ADHD. Most of our findings could not be accounted for by co
      morbidity, underlining the importance of targeting treatment at ADHD itself.
      FUNDING: This research was funded by The Psychiatric Research Foundation of the
      Central Denmark Region. TRIAL REGISTRATION: not relevant.

PMID- 25748870
TI  - Operative treatment with nerve repair can restore function in patients with
      traction injuries in the brachial plexus.
AB  - INTRODUCTION: Brachial plexus injuries are usually a result of road traffic
      accidents and a cause of severe disability that typically affects young adult
      males. In 2010, a national centre was established for referral of these cases
      from Danish trauma centres. In this paper, we report on our surgical activity and
      reflect on the role for this new national centre. METHODS: Records from all our
      operated patients were reviewed retrospectively. For outcome analysis, we focused
      on patients who had sustained traction injuries with a surgical follow-up
      exceeding one year. We used either nerve grafting or transfers for nerve repairs
      based on the pattern of nerve injury seen intraoperatively. RESULTS: Overall, 24
      patients were operated, and 12 patients were included in the outcome analysis.
      The six patients with upper brachial plexus palsies all regained shoulder
      function and useful elbow flexion. Of the six patients with complete brachial
      plexus palsies, four regained shoulder function, while only one regained useful
      elbow function, and this was after nerve transfers. CONCLUSION: Operative
      treatment provides satisfactory results in patients with upper brachial plexus
      palsies, while improvement is warranted in patients with complete brachial plexus
      palsies. Our data suggest that nerve transfers may result in a better functional
      outcome than nerve grafting. We believe that there is a role for a Danish centre
      for the treatment of these injuries. FUNDING: not relevant. TRIAL REGISTRATION:
      not relevant.

PMID- 25748871
TI  - Endoscopic ultrasonography is a valuable diagnostic tool in patients with
      incidental findings in the pancreas or bile ducts.
AB  - INTRODUCTION: Incidental findings are often seen at computed tomographies (CT).
      This study describes patients who had an endoscopic ultrasonography (EUS) because
      of an incidental finding in the pancreas/bile duct. METHODS: Patients referred
      for EUS between September 2012 and September 2013 because of an incidental
      finding in the pancreas/bile duct at a CT were prospectively enrolled. After EUS,
      the findings of this procedure were noted together with the plan for further
      diagnostic work-up or therapy. A follow-up was made after 6 months and 1 year
      after EUS was performed. RESULTS: A total of 47 patients (24 women, 23 men) were
      registered with an incidental finding. The median age was 69 years (range: 45-83
      years). Diagnoses after performing EUS were: normal findings (n = 16), cystic
      lesion (n = 16), mass lesion (n = 6), inconclusive (n = 6) and other specified (n
      = 3). The plan after EUS was: no further evaluation (n = 27), referred for new
      EUS or other imaging procedures (n = 14) and referred for surgery/endoscopic
      retrograde cholangiopancreatography (n = 6). In total, 6 patients proved to have
      neoplastic diseases in the pancreas. None of the patients who were stopped from
      further evaluation following EUS later proved to have a malignant disease in the
      pancreas. CONCLUSION: EUS is a valuable diagnostic tool in patients with
      incidental findings in the pancreas/bile duct noted at a CT. Many patients can be
      stopped from further diagnostic work-up after EUS with a minimal risk of
      overlooking a malignant disease. FUNDING: not relevant. TRIAL REGISTRATION: The
      study was approved by the Danish Data Protection Agency via Region of Southern
      Denmark (case no. 13/27,321).

PMID- 25748872
TI  - Danish Guidelines 2015 for percutaneous dilatational tracheostomy in the
      intensive care unit.
AB  - Percutaneous dilatational tracheostomy is a common procedure in intensive care.
      This updated Danish national guideline describes indications, contraindications
      and complications, and gives recommendations for timing, anaesthesia, and
      technique, use of fibre bronchoscopy and ultrasound guidance, as well as
      decannulation strategy, training, and education. 

PMID- 25748873
TI  - Surgical treatment of functional ischemic mitral regurgitation.
AB  - In many ways we are at a crossroad in terms of what constitutes optimal FIMR
      treatment: is CABG combined with mitral valve ring annuloplasty better than CABG
      alone in moderate FIMR? Is mitral valve repair really better than replacement?
      And does adding a valvular repair or subvalvular reverse remodeling procedure
      shift that balance? In the present thesis I aim to shed further light on these
      questions by addressing the current status and future perspectives of the
      surgical treatment of FIMR. CURRENT SURGICAL TREATMENT FOR FIMR. CABG alone: The
      overall impression from the literature is that patients are left with a high
      grade of persistent/recurrent FIMR from isolated CABG. CABG is most effective to
      treat FIMR in patients with viable myocardium (at least five viable segments) and
      absence of dyssynchrony between papillary muscles (< 60 ms). Mitral valve ring
      annuloplasty. A vast number of different designs are available to perform mitral
      valve ring annuloplasty with variations over the theme of complete/partial and
      rigid/semi-rigid/flexible. Also, the three-dimensional shape of the rigid and
      semi-rigid rings is the subject of great variation. A rigid or semi-rigid down
      sized mitral valve ring annuloplasty is the most advocated treatment in chronic
      FIMR grade 2+ or higher. Combined CABG and mitral valve ring annuloplasty: CABG
      combined with mitral valve ring annuloplasty leads to reverse LV remodeling and
      reduced volumes. Despite this, the recurrence rate after combined CABG and mitral
      valve ring annuloplasty is 20-30% at 2-4 years follow-up. This is also true for
      studies strictly using down-sized mitral valve ring annuloplasty by two sizes. A
      number of preoperative risk factors to develop recurrent FIMR were identified,
      e.g. LVEDD > 65-70 mm, coaptation depth > 10 mm, anterior leaflet angle > 27-39.5
      degrees , posterior leaflet angle > 45 degrees  and interpapillary muscle
      distance > 20 mm. CABG alone vs. combined CABG and mitral valve ring
      annuloplasty: The current available literature, including three randomized
      studies and a meta analysis, indicate that combined CABG and mitral valve ring
      annuloplasty has no late survival difference compared with CABG alone, and early
      mortality might even be higher. Meanwhile, adding a mitral valve ring
      annuloplasty results in a lower NYHA functional class, most likely as a
      consequence of a lower incidence of persistent or recurrent FIMR. More randomized
      studies are being conducted to further address this topic. Mitral valve ring
      annuloplasty vs. mitral valve replacement. The early survival may be higher after
      repair compared with replacement, meanwhile, the literature is more ambiguous in
      terms of late survival advantages, and recent reports find no late survival
      advantage from repair over replacement. The recurrence rates after ring
      annuloplasty addressed above were also present in this subset of patients,
      whereas the incidence of recurrent FIMR after valve replacement is scarcely
      reported. There was an overall tendency of slightly higher incidence of
      reoperations after ring annuloplasty. The mitral valve annulus: Innovations in
      mitral valve ring annuloplasty: The latest innovation in mitral valve ring
      annuloplasty design includes adjustable rings, allowing adjustment of septo
      lateral dimensions intra- or postoperatively. Minimally invasive ring
      annuloplasty using indirect coronary sinus devices, has been introduced, but so
      far have produced suboptimal results in terms of safety and efficacy. Also, first
      in man testing of direct percutaneous catheter based mitral annuloplasty
      techniques have been conducted. Leaflets and chordae: Direct repair techniques:
      Surgical methods have been developed to directly address the mitral valve
      leaflets and chordae tendineae to correct leaflet tethering in FIMR. Both the
      Alfieri stich and the minimally invasive MitraClip attaches the anterior and
      posterior leaflets, typically the A2-P2 region, to correct incomplete leaflet
      coaptation. Patch augmentation of the posterior leaflet in the P2-P3 region
      increases coaptation in the area most prone to cause FIMR. Chordal cutting of the
      secondary "strut" chordae releases the anterior leaflet from the tethering due to
      papillary muscle displacement and improves mitral valve geometry. The mitral
      subvalvular apparatus: Numerous subvalvular approaches to improve outcome in
      patients with FIMR have been introduced. They include very invasive techniques
      such as surgical ventricular restoration procedure, surgical techniques directly
      addressing the papillary muscle dis-placement, and beating heart procedures using
      transventricular and epicardial devices applied in a few minutes. The role of the
      transventricular and epicardial devices still remains to be defined and many of
      these devices seem to have a hard time ganing their footing in the clinical
      practise and until now only constitute a footnote in the surgical literature.
      Meanwhile, the current results with adjunct techniques to CABG and ring
      annuloplasty, such as the papillary muscle approximation technique introduced by
      Hvass et al and the papillary muscle relocation technique introduced by Kron et
      al and further developed by Langer et al are gaining continuing support in the
      surgical community since these techniques can be used with only little added time
      consumption but with very good clinical outcome.

PMID- 25748874
TI  - Blood pressure and arterial stiffness in obese children and adolescents.
AB  - Obesity, elevated blood pressure (BP) and arterial stiffness are risk factors for
      cardiovascular disease. A strong relationship exists between obesity and elevated
      BP in both children and adults. Obesity and elevated BP in childhood track into
      adult life increasing the risk of cardiovascular disease in adulthood. Ambulatory
      BP is the most precise measure to evaluate the BP burden, whereas carotid-femoral
      pulse wave velocity (cfPWV) is regarded as the gold standard for evaluating
      arterial (i.e. aortic) stiffness. These measures might contribute to a better
      understanding of obesity's adverse impact on the cardiovascular system, and
      ultimately a better prevention and treatment of childhood obesity. The overall
      aim of the present PhD thesis is to investigate arterial stiffness and 24-hour BP
      in obese children and adolescents, and evaluate whether these measures are
      influenced by weight reduction. The present PhD thesis is based on four
      scientific papers.  In a cross-sectional design, 104 severe obese children and
      adolescents with an age of 10-18 years were recruited when newly referred to the
      Children's Obesity Clinic, Holbaek University Hospital, and compared to 50 normal
      weighted age and gender matched control individuals. Ambulatory BP was measured,
      and cfPWV was investigated in two ways in respect to the distance measure of
      aorta; the previously recommended length - the so called subtracted distance, and
      the currently recommended length - the direct distance. In a longitudinal design,
      the obese patients were re-investigated after one-year of lifestyle intervention
      at the Children's Obesity Clinic in purpose of reducing the degree of obesity. In
      the cross-sectional design, the obese group had higher measures of obesity, while
      matched for age, gender and height, when compared to the control group. In the
      longitudinal design, 74% of the 72 followed up obese patients experienced a
      significant weight reduction. CfPWV was dependent on the method used to measure
      the length of the aorta. The subtracted distance was not consistent in its
      relation to height in the obese and the control group. Opposite, the direct
      distance was consistent in its relation to height in the two groups. Therefore,
      cfPWV using the direct distance (cfPWV-direct) was regarded as the appropriate
      measure of arterial stiffness. CfPWV-direct was reduced in the obese group after
      adjustment for known confounders. In the longitudinal design, weight reduction
      across one year did not have an impact on cfPWV-direct in the obese patients. In
      fact, cfPWV-direct was higher at follow-up, which was explained by the increased
      age and partly by changes in BP and heart rate. The obese group had a relatively
      higher night- than day-time BP when compared to the control group. The obesity
      related elevated night-time BP was independent of arterial stiffness and insulin
      resistance. Although night-time systolic BP was related to arterial stiffness and
      tended to be related to insulin resistance, insulin resistance and arterial
      stiffness were not related. In the longitudinal design, changes in anthropometric
      obesity measures across one year were associated with changes in 24-hour, day-
      and night-time BP, and consistent when evaluated in standardised values that
      accounted for growth. No association was found between changes in anthropometric
      obesity measures and changes in clinic BP. In conclusion, the results suggest
      that obesity in children is not "yet" associated with structural changes in aorta
      when evaluated with the appropriate new method of cfPWV. In this respect, weight
      reduction did not have an impact on arterial stiffness. The ambulatory BP, namely
      the night-time BP, was elevated in the obese patients, whereas changes in
      anthropometric obesity measures were related to changes in ambulatory BP but not
      to changes in clinic BP. In perspective, it is reassuring that weight changes are
      accompanied with a change in 24-hour BP as ambulatory BP is the most precise
      measure to evaluate the BP burden, and it emphasises the use of 24-hour
      ambulatory BP measurements in children and adolescents. It is important to
      recognise, that obese children who recover their normal weight before adulthood
      will have a similar cardiovascular risk as those who were never obese. Hence,
      early treatment and prevention of childhood obesity is important because it may
      prevent irreversible damage to the cardiovascular system. 

PMID- 25748875
TI  - Faecal retention: a common cause in functional bowel disorders, appendicitis and
      haemorrhoids--with medical and surgical therapy.
AB  - The present studies explored whether faecal retention in the colon is a causative
      factor in functional bowel disease, appendicitis, and haemorrhoids. Faecal
      retention was characterized by colon transit time (CTT) after radio-opaque marker
      ingestion and estimation of faecal loading on abdominal radiographs at 48 h and
      96 h. Specific hypotheses were tested in patients (n = 251 plus 281) and in
      healthy random controls (n = 44). A questionnaire was completed for each patient,
      covering abdominal and anorectal symptoms and without a priori grouping. Patients
      with functional bowel disorders, predominantly women, had a significantly
      increased CTT and faecal load compared to controls. The CTT was significantly and
      positively correlated with segmental and total faecal loading. The faecal load
      was equal at 48 h and 96 h, mirroring the presence of permanent faecal
      reservoirs. In these first clinical studies to correlate bowel symptoms with CTT
      and colon faecal loading, abdominal bloating was significantly correlated with
      faecal loading in the right colon, total faecal load, and CTT. Abdominal pain was
      significantly and positively correlated to distal faecal loading and
      significantly associated with bloating. A new phenomenon with a high faecal load
      and a normal CTT was observed in a subset of patients (n = 90), proving faecal
      retention as hidden constipation. The CTT and faecal load were significantly
      higher in the right-side compared to the left and distal segments. Within the
      control group of healthy persons, the right-sided faecal load was significantly
      greater than the left and distal load. The CTT and faecal load significantly
      positively correlated with a palpable mass in the left iliac fossa and meteorism.
      Cluster analysis revealed that CTT and faecal load positively correlated with a
      symptom factor consisting of bloating, proctalgia and infrequent defecation of
      solid faeces. On the other hand, CTT and faecal load negatively correlated with a
      symptom factor comprising frequent easy defecations, repetitiveness, and
      incompleteness with solid or liquid faeces. The majority of patients with a heavy
      faecal load but normal CTT had repetitive daily defecation, mostly with ease and
      with altering faecal consistence. Flue-like episodes co-existed in symptom
      factors with abdominal pain and meteorism, and these symptoms together with a
      palpable right iliac fossa mass and tenderness, and in other factors with seldom
      and difficult defecation, and with epigastric discomfort and halitosis. Patients
      with seldom and difficult defecation of solid faeces experienced abdominal pain
      significantly more often and presented a palpable mass in the right iliac fossa
      with tenderness and meteorism. The CTT was significantly prolonged and faecal
      load significantly increased. In patients with a normal CTT and increased faecal
      load, only patients with abdominal pain had a significant correlation between
      faecal loading and bloating. CTT and faecal load were shown for the first time to
      increase significantly with the number of colonic redundancies (colon length),
      which also resulted in significantly increased bloating and pain. Intervention
      with a bowel stimulation regimen combining a fibre-rich diet, fluid, physical
      activity, and a prokinetic drug was essential to proving that abdominal symptoms
      and defecation disorders are caused by faecal retention, with or without a
      prolonged CTT. The CTT was significantly reduced, as was faecal load. Bloating
      and pain were reduced significantly. The defecation became easy with solid
      faeces, towards one per day and with significant reductions in incompleteness and
      repetitiveness. Proctalgia and flue-like episodes were significantly reduced. The
      intervention significantly reduced the presence of a tender palpable mass in the
      right fossa and rectal constipation. In patients with a normal CTT but increased
      faecal load, the intervention did not significantly change the CTT or load, but
      bloating and pain were significantly reduced, just as defecation improved
      overall. The novel knowledge of faecal retention in the patients does not explain
      why faecal retention occurs. However, it may be inferred from the present results
      that a constipated or irritable bowel may belong to the same underlying disease
      dimension, where faecal retention is a common factor. Thus, measuring CTT and
      faecal load is suggested as a guide to a positive functional diagnosis of bowel
      disorders compared to the constellation of symptoms alone. Thirty-five patients
      underwent surgery after being refractory to the conservative treatment for
      constipation. They had a significantly prolonged CTT and heavy faecal loading,
      which was responsible for the aggravated abdominal and defaecatory symptoms. The
      operated patients presented with a redundant colon (dolichocolon) significantly
      more often. These patients also had an extremely high rate of previous
      appendectomy. Twenty-one patients underwent hemicolectomy, and 11 patients had a
      subtotal colectomy with an ileosigmoidal anastomosis; three patients received a
      stoma. However, some patients had to have the initial segmental colectomy
      converted to a final subtotal colectomy because of persisting symptoms. Six more
      subtotal colectomies have been performed and the leakage rate of all colectomies
      is then 4.9 % (one patient died). After a mean follow-up of 5 years, the vast
      majority of patients were without abdominal pain and bloating, having two to four
      defecations daily with control and their quality of life had increased
      considerably. A faecalith is often located in the appendix, the occlusion of
      which is responsible for many cases of acute appendicitis, which is infrequent in
      all except white populations. An effort to trace the origin of the faecalith to
      faecal retention in the colon was made in a case control study (56 patients and
      44 random controls). The CTT was longer and faecal load greater in patients with
      appendicitis compared to controls, though the difference was not significant.
      Power calculations showed that more patients were needed to reach statistical
      significance for these parameters. The presence of a faecalith was most often
      associated with a gangrenous or perforated appendix. No significant differences
      were found between the CTT and faecal load of patients who had or did not have a
      faecalith. However, the right-sided faecal load was significantly higher than the
      left and distal load. Haemorrhoids are often a consequence of constipation and
      defaecatory disorders and were found in every second patient with functional
      bowel disorders. The present studies are the first Danish reports of a novel
      operation to cure this disease, stapled haemorrhoidopexy (n = 40 and 258
      patients). The majority of patients had prolapsed haemorrhoids, and the
      durability of procedure was confirmed with a follow-up of up to 5 years, meaning
      a normal anus. The operation time was short, post-operative pain was low, and
      recovery was rapid. No incontinence was observed, and patient satisfaction was
      high and significantly correlated with the appearance of a normal anus without
      prolapse. The cumulative risk of re-operation was greatest in the first 2 years
      after the stapled haemorrhoidopexy. Patients with persisting haemorrhoidal
      prolapse had the procedure repeated with results as good as those obtained in the
      rest of the patients. It was shown in a statistical model that the preoperative
      severity of haemorrhoidal disease and the immediate postoperative result
      contributed significantly to predicting the outcome that is the durability of the
      operation. The most frequent post-operative complication was bleeding requiring
      surgical haemostasis. One serious complication occurred after an anastomotic leak
      from a highly placed anastomosis, resulting in retro rectal, retro- and intra
      peritoneal, and mediastinal gas. The patient recovered after conservative
      treatment and without surgical intervention. The stapling technique now used has
      revolutionized the surgical treatment of prolapsing haemorrhoids. Finally, a
      common cause may be suspected for diseases constantly associated with one
      another. Epidemiological evidence has recognized that constipation,
      diverticulosis and IBS increase the risk of colon cancer (and adenomas), diseases
      exceedingly rare in communities exempt from appendicitis. Haemorrhoids are a
      colonic co-morbidity as well. Notably, the patients with a functional bowel
      disorder had a much higher rate of a previous appendectomy than the background
      population. In addition, the patients who had previously had an appendectomy had
      a significantly longer CTT compared to patients, who had not. The data points to
      the involvement of faecal retention in the origin of faecaliths and, thus, acute
      appendicitis. Faecal reservoirs were shown in the right and left colon segments
      in both patients and controls, which are the same areas bearing the highest
      incidences of adenomateous polyps and malignancies. Familial colorectal cancer
      occurred significantly more often in patients who had a higher faecal load than
      the controls. Four malignancies and 25 adenomas were identified. An increased
      faecal load in the colon with or without delayed transit will increase bacterial
      counts and create a chronic inflammation of the colonic mucosa, which is a risk
      factor for cancer onset. A functional bowel disorder is then likely to occur with
      gradually transition from a primary functional disease into specific organic
      diseases. A diet rich in fibre and regular physical activity have a therapeutic
      and preventive effect on colorectal diseases associated with faecal retention. A
      "common cause" was earlier proposed for constipation, colon diverticula, cancer,
      appendicitis, and haemorrhoids. The actual results of the present studies support
      this unifying theory for these diet-related diseases, in which the functional
      retention of faeces maybe the common cause.

PMID- 25748876
TI  - The effect of direct referral for fast CT scan in early lung cancer detection in
      general practice. A clinical, cluster-randomised trial.
AB  - This PhD thesis is based on the project "The effect of direct referral for fast
      CT scan in early lung cancer detection in general practice. A clinical, cluster
      randomised trial", performed in Denmark in 2010-2013. The thesis includes four
      papers and focuses on early lung cancer diagnostics in general practice.
      INTRODUCTION: A total of 4200 new cases of lung cancer are diagnosed in Denmark
      annually. The stage of the disease is an important prognostic factor; thus, the
      opportunity for curative treatment declines with more advanced tumour stage. Lung
      cancer patients in Denmark (like in the UK) have a poorer prognosis than lung
      cancer patients in other European countries. One explanation could be delayed
      diagnosis. A fast-track pathway was therefore introduced in an attempt to
      expedite the diagnosis of cancer. However, it seems that not all patients can be
      diagnosed through this pathway. In order to ensure fast and early lung cancer
      diagnosis, it is crucial to examine the initial diagnostic process in general and
      the role general practice plays in lung cancer diagnostics in particular. The
      specific areas of investigation include the pathways to diagnosis, the
      characteristics of patients who are at special risk of delayed diagnosis and the
      level of prediagnostic activity in general practice. A chest radiograph is often
      the first choice in the investigation of lung cancer. Unfortunately, radiographs
      are less suitable for central and small tumours. Low-dose computer tomography
      (LDCT), however, has a high sensitivity for lung cancer which implies that it can
      be used to detect patients with localised, potentially curable disease. AIM: The
      aim of this thesis was to increase our knowledge of the initial stages of lung
      cancer diagnostics in general practice. The thesis also examined the effect of a
      direct referral from general practice to an additional diagnostic test, the LDCT.
      The aims of this thesis were: 1) To describe Danish patients' pathways to the
      diagnosis of lung cancer in general and the prediagnostic activity leading up to
      diagnosis in particular. An additional aim was to explore the diagnostic
      intervals for specific patient groups (Paper I). 2) In a randomised, controlled
      trial including all patients referred for the existing fast-track scheme to
      either direct chest and upper abdomen CE-MDCT or to evaluation by the chest
      physician, (i) to test: Fast-track performance measured by the number of CE-MDCT
      scans and chest physician specialist time per diagnosis  (Paper II) 3) In a two
      arm, clinical, controlled, cluster-randomised trial where direct referral to CT
      together with a lung cancer update is compared with usual practice, (i) to test
      how CT is used in this group of patients and the outcome of CT (Paper III); and
      (ii) to test the effect of either modality on the time to lung cancer diagnosis,
      the TNM stage and the use of the fast-track pathway for lung cancer (Paper IV).
      METHODS: Study I was a national registry-based cohort study of 971 consecutive,
      incident lung cancer patients in 2010 Data were derived from national registries
      and questionnaires filled in by general practitioners (GPs). Study II was a
      randomised, controlled trial enrolling 493 patients referred from general
      practice to a fast-track evaluation. Half of the patients were randomly assigned
      to the intervention and went straight to a chest CT before a chest physician
      evaluation. Studies III and IV were a cluster-randomised, controlled trial (IV)
      and a cohort study nested in the trial (III). A total of 199 general practices
      with 266 GPs were randomised into two groups. Intervention GPs were offered
      direct access to a low-dose chest CT combined with a meeting on early lung cancer
      detection. Study III concerned the intervention arm solely and reported uses and
      outcomes of the scans. Study IV evaluated the effect of direct low-dose CT on the
      time to diagnosis and stage at diagnoses for patients from intervention and
      control GPs. RESULTS: In Study I, we found that GPs were involved in 2/3 of all
      lung cancer diagnostic pathways. One quarter of the patients followed the obvious
      pathway from general practice to fast-track detection. At least one radiograph
      was performed in 85.6% of patients, whereas 1/3 of all patients had two or more
      radiograph performed during the 90 days preceding diagnosis. Patients with co
      morbidity or unspecific symptoms more often had two or more X-rays performed than
      patients without these characteristics. In Study II, there was no difference
      between the groups in the number of CTs performed. In the intervention group,
      chest physicians spent mean 13.3 minutes less per referred patient than in the
      control group. In Study III, we found that 648 patients were referred to low-dose
      CT during a 19-month period. Half of the referred patients needed further work
      up, and 15 (2.3%) of the patients had lung cancer, 60% in a localised stage. For
      all patients, 6.8% were diagnosed with a severe lung disease. In all, 2/3 of the
      GPs used the CT opportunity; and the referral rate was 61% higher for GPs
      participating in the lung cancer meeting than for GPs who did not participate in
      such meetings. In Study IV, we found that direct, low-dose CT from primary care
      did not significantly influence stage at diagnosis and had only a limited impact
      on time to diagnosis. CONCLUSION AND PERSPECTIVES: This thesis contributes to the
      knowledge of the early diagnosis of lung cancer in Denmark. General practice was
      found to play an important role, but only a small part of Danish lung cancer
      patients were diagnosed from general practice through the fast-track pathway.
      This together with the fact that a high proportion of patients had two or more
      radiographs within the 90 days preceding the diagnosis indicate that other
      diagnostic strategies should be tested in an attempt to provide GPs with the best
      opportunity for early diagnosis. This thesis provides evidence that GPs are,
      indeed, able to refer patients straight-to-test in the fast-track pathway. This
      knowledge may be used when organising other fast tracks. Furthermore, GPs
      participating in education about early lung cancer diagnosis were willing to
      refer patients direct to low-dose CT (LDCT) from primary care. Half of the
      patients needed further diagnostic work-up, and 2.3% of all patients referred
      were diagnosed with lung cancer. In addition, many lung diseases were diagnosed
      by LDCT. No effect on time to diagnosis or stage at diagnosis was found when
      patients from intervention GPs were compared with patients from control GPs. The
      effect of combining direct access to LDCT with referral to the existing fast
      track pathway should be analysed as it may ensure earlier and faster lung cancer
      detection in primary care. Direct access to LDCT scan may also be an alternative
      to lung cancer screening. Furthermore, if a LDCT screening program is going to be
      implemented, it should be considered to supplement the program with access to CT
      directly from primary care for the symptomatic, not-screened patients.

PMID- 25748878
TI  - Exploring the performance of the National Early Warning Score (NEWS) in a
      European emergency department.
AB  - BACKGROUND: Several triage systems have been developed for use in the emergency
      department (ED), however they are not designed to detect deterioration in
      patients. Deteriorating patients may be at risk of going undetected during their
      ED stay and are therefore vulnerable to develop serious adverse events (SAEs).
      The national early warning score (NEWS) has a good ability to discriminate ward
      patients at risk of SAEs. The utility of NEWS had not yet been studied in an ED.
      OBJECTIVE: To explore the performance of the NEWS in an ED with regard to
      predicting adverse outcomes. DESIGN: A prospective observational study. Patients
      Eligible patients were those presenting to the ED during the 6 week study period
      with an Emergency Severity Index (ESI) of 2 and 3 not triaged to the
      resuscitation room. INTERVENTION: NEWS was documented at three time points: on
      arrival (T0), hour after arrival (T1) and at transfer to the general ward/ICU
      (T2). The outcomes of interest were: hospital admission, ICU admission, length of
      stay and 30 day mortality. RESULTS: A total of 300 patients were assessed for
      eligibility. Complete data was able to be collected for 274 patients on arrival
      at the ED. NEWS was significantly correlated with patient outcomes, including 30
      day mortality, hospital admission, and length of stay at all-time points.
      CONCLUSION: The NEWS measured at different time points was a good predictor of
      patient outcomes and can be of additional value in the ED to longitudinally
      monitor patients throughout their stay in the ED and in the hospital.

PMID- 25748879
TI  - Effects of a reduced disulfide bond on aggregation properties of the human IgG1
      CH3 domain.
AB  - Recombinant human monoclonal antibodies have become important protein-based
      therapeutics for the treatment of various diseases. An IgG1 molecule, which is
      now mainly used for antibody preparation, consists of a total of 12
      immunoglobulin domains. Each domain has one disulfide bond. The CH3 domain is the
      C-terminal domain of the heavy chain of IgG1. The disulfide bonds of some of the
      CH3 domains are known to be reduced in recombinant human monoclonal antibodies.
      The lack of intramolecular disulfide bonds may decrease the stability and
      increase the aggregation propensity of an antibody molecule. To investigate the
      effects of a reduced disulfide bond in the CH3 domain on conformational stability
      and aggregation propensity, we performed several physicochemical measurements
      including circular dichroism, differential scanning calorimetry (DSC), and 2D
      NMR. DSC measurements showed that both the stability and reversibility of the
      reduced form were lower than those of the oxidized form. In addition, detailed
      analyses of the thermal denaturation data revealed that, although a dominant
      fraction of the reduced form retained a stable dimeric structure, some fractions
      assumed a less-specifically associated oligomeric state between monomers. The
      results of the present study revealed the characteristic aggregation properties
      of antibody molecules. 

PMID- 25748880
TI  - Critical determinants for substrate recognition and catalysis in the M.
      tuberculosis class II AP-endonuclease/3'-5' exonuclease III.
AB  - The Mycobacterium tuberculosis AP-endonuclease/3'-5' exodeoxyribonuclease
      (MtbXthA) is an important player in DNA base excision repair (BER). We
      demonstrate that the enzyme has robust apurinic/apyrimidinic (AP) endonuclease
      activity, 3'-5' exonuclease, phosphatase, and phosphodiesterase activities. The
      enzyme functions as an AP-endonuclease at high ionic environments, while the 3'
      5'-exonuclease activity is predominant at low ionic environments. Our molecular
      modelling and mutational experiments show that E57 and D251 are critical for
      catalysis. Although nicked DNA and gapped DNA are fair substrates of MtbXthA, the
      gap-size did not affect the excision activity and furthermore, a substrate with a
      recessed 3'-end is preferred. To understand the determinants of abasic-site
      recognition, we examined the possible roles of (i) the base opposite the abasic
      site, (ii) the abasic ribose ring itself, (iii) local distortions in the AP-site,
      and (iv) conserved residues located near the active site. Our experiments
      demonstrate that the first three determinants do not play a role in MtbXthA, and
      in fact the enzyme exhibits robust endonucleolytic activity against single
      stranded AP DNA also. Regarding the fourth determinant, it is known that the
      catalytic-site of AP endonucleases is surrounded by conserved aromatic residues
      and intriguingly, the exact residues that are directly involved in abasic site
      recognition vary with the individual proteins. We therefore, used a combination
      of mutational analysis, kinetic assays, and structure-based modelling, to
      identify that Y237, supported by Y137, mediates the formation of the MtbXthA-AP
      DNA complex and AP-site incision. 

PMID- 25748882
TI  - The spatial profile of mask-induced compression for perception and action.
AB  - Stimuli briefly flashed just before a saccade are perceived closer to the saccade
      target, a phenomenon known as saccadic compression of space. We have recently
      demonstrated that similar mislocalizations of flashed stimuli can be observed in
      the absence of saccades: brief probes were attracted towards a visual reference
      when followed by a mask. To examine the spatial profile of this new phenomenon of
      masked-induced compression, here we used a pair of references that draw the probe
      into the gap between them. Strong compression was found when we masked the probe
      and presented it following a reference pair, whereas little or no compression
      occurred for the probe without the reference pair or without the mask. When the
      two references were arranged vertically, horizontal mislocalizations prevailed.
      That is, probes presented to the left or right of the vertically arranged
      references were "drawn in" to be seen aligned with the references. In contrast,
      when we arranged the two references horizontally, we found vertical compression
      for stimuli presented above or below the references. Finally, when participants
      were to indicate the perceived probe location by making an eye movement towards
      it, saccade landing positions were compressed in a similar fashion as perceptual
      judgments, confirming the robustness of mask-induced compression. Our findings
      challenge pure oculomotor accounts of saccadic compression of space that assume a
      vital role for saccade-specific signals such as corollary discharge or the
      updating of eye position. Instead, we suggest that saccade- and mask-induced
      compression both reflect how the visual system deals with disruptions. 

PMID- 25748881
TI  - Introduction of germline residues improves the stability of anti-HIV mAb 2G12
      IgM.
AB  - Immunoglobulins M (IgMs) are gaining increasing attention as biopharmaceuticals
      since their multivalent mode of binding can give rise to high avidity.
      Furthermore, IgMs are potent activators of the complement system. However, they
      are frequently difficult to express recombinantly and can suffer from low
      conformational stability. Here, the broadly neutralizing anti-HIV-1 antibody 2G12
      was class-switched to IgM and then further engineered by introduction of 17
      germline residues. The impact of these changes on the structure and
      conformational stability of the antibody was then assessed using a range of
      biophysical techniques. We also investigated the effects of the class switch and
      germline substitutions on the ligand-binding properties of 2G12 and its capacity
      for HIV-1 neutralization. Our results demonstrate that the introduced germline
      residues improve the conformational and thermal stability of 2G12-IgM without
      altering its overall shape and ligand-binding properties. Interestingly, the
      engineered protein was found to exhibit much lower neutralization potency than
      its wild-type counterpart, indicating that potent antigen recognition is not
      solely responsible for IgM-mediated HIV-1 inactivation. 

PMID- 25748883
TI  - Evaluating the effects of charged oligopeptide motifs coupled with RGD on
      osteogenic differentiation of mesenchymal stem cells.
AB  - Mesenchymal stem cells, due to their multilineage differentiation potential, have
      emerged as a promising cell candidate for cell-based therapy. In recent years,
      biomaterials were artificially synthesized to control the differentiation of
      mesenchymal stem cells. In this study, a series of charged or neutral
      oligopeptide motifs coupled with RGD were synthesized and used for surface
      modification using quartz substrates as model. Cell behaviors on the modified
      surfaces with different charged oligopeptide motifs were studied. It was found
      that these different charged oligopeptide motifs coupled with RGD were
      biocompatible for cell proliferation and adhesion. Moreover, it was demonstrated
      that the positively charged oligopeptide motif could inhibit osteogenic
      differentiation, while the negatively charged and neutral oligopeptide motifs
      could enhance osteogenic differentiation in the presence of RGD. This work may
      bring us enlightenment that different charged oligopeptide motifs coupled with
      RGD may be used for biomaterial surface modification for different stem cell
      based therapies. 

PMID- 25748885
TI  - Clinical characteristics and outcomes on discharge of women admitted to a Medium
      Secure Unit over a 4-year period.
AB  - There are limited data on women in Medium Secure settings. This study aimed to
      address this by assessing the characteristics of 45 consecutive admissions to the
      female ward of a Medium Secure Unit in the United Kingdom over a four-year
      period. Data on demographics, clinical outcomes and from HONOS-Secure/HONOS and
      HCR-20 assessments were prospectively collected. Psychiatric diagnoses were
      recorded using ICD-10 criteria. Data on quality of life from WHO-QoL-BREF surveys
      were analysed. There was a high proportion of ethnic minorities (57.8%), high
      rates of childhood and adult abuse and low socioeconomic status. 62.2% of the
      patients had schizophrenia, 57.8% had multiple diagnoses. The median length of
      stay at discharge was 465.5 days. There were statistically significant reductions
      in rates of self-harm and HoNOS-Secure/HoNOS and HCR-20 scores following
      intervention. Scores on WHO-QoL-BREF compared favourably to a large-scale sample
      with mental health difficulties. Many characteristics of this sample were
      comparable to samples from similar populations. However the particularly high
      proportion of ethnic minorities suggested that the profile of our patients
      differs from nationwide samples. Intervention by our service was associated with
      reduced self-harm and improvements in well-defined clinical outcomes and quality
      of life measures using validated scales.

PMID- 25748886
TI  - Outpatient commitment and procedural due process.
AB  - A large empirical literature on Kendra's Law has assessed the impact of court
      ordered outpatient treatment on outcomes such as treatment adherence, psychiatric
      hospitalization, quality of life, and treatment costs. Missing from the empirical
      literature, however, is a better understanding of procedural due process under
      Kendra's Law. Procedural due process concerns the safeguards that must be in
      place when governments deprive persons of their liberties, for example--notice,
      the right to a hearing and the right to appeal. This article reports the findings
      from a qualitative study of procedural due process and assisted outpatient
      treatment hearings under Kendra's Law. Attorneys reported significant barriers to
      effective advocacy on behalf of their clients. Further, despite the shift from a
      medical model of civil commitment to a judicial model in the 1970s, by and large
      judges continue to accord great deference to clinical testimony.

PMID- 25748884
TI  - Disrupted fornix integrity in children with chromosome 22q11.2 deletion syndrome.
AB  - The fornix is the primary subcortical output fiber system of the hippocampal
      formation. In children with 22q11.2 deletion syndrome (22q11.2DS), hippocampal
      volume reduction has been commonly reported, but few studies as yet have
      evaluated the integrity of the fornix. Therefore, we investigated the fornix of
      45 school-aged children with 22q11.2DS and 38 matched typically developing (TD)
      children. Probabilistic diffusion tensor imaging (DTI) tractography was used to
      reconstruct the body of the fornix in each child's brain native space. Compared
      with children, significantly lower fractional anisotropy (FA) and higher radial
      diffusivity (RD) was observed bilaterally in the body of the fornix in children
      with 22q11.2DS. Irregularities were especially prominent in the posterior aspect
      of the fornix where it emerges from the hippocampus. Smaller volumes of the
      hippocampal formations were also found in the 22q11.2DS group. The reduced
      hippocampal volumes were correlated with lower fornix FA and higher fornix RD in
      the right hemisphere. Our findings provide neuroanatomical evidence of disrupted
      hippocampal connectivity in children with 22q11.2DS, which may help to further
      understand the biological basis of spatial impairments, affective regulation, and
      other factors related to the ultra-high risk for schizophrenia in this
      population. 

PMID- 25748887
TI  - Incidence of functional bi-temporal connections in the human brain in vivo and
      their relevance to epilepsy surgery.
AB  - The incidence of functional connections between human temporal lobes and their
      latencies were investigated using intracranial EEG responses to electrical
      stimulation with 1 msec single pulses in 91 patients assessed for surgery for
      treatment of epilepsy. The areas studied were amygdala, hippocampus,
      parahippocampal gyrus, fusiform gyrus, inferior and mid temporal gyrus.
      Furthermore, we assessed whether the presence of such connections are related to
      seizure onset extent and postsurgical seizure control. Responses were seen in any
      region of the contralateral temporal lobe when stimulating temporal regions in 30
      patients out of the 91 (32.96%). Bi-hippocampal or bi-amygdalar projections were
      seen in only 5% of temporal lobes (N = 60) and between both fusiform gyri in 7.1%
      (N = 126). All other bilateral connections occurred in less than 5% of
      hemispheres. Depending on the structures, latencies ranged between 20 and 90
      msec, with an average value of 60.2 msec. There were no statistical difference in
      the proportion of patients showing Engel Class I between patients with and
      without contralateral temporal connections. No difference was found in the
      proportion of patients showing bilateral or unilateral seizure onset among
      patients with and without contralateral temporal projections. The present
      findings corroborate that the functionality of bilateral temporal connections in
      humans is limited and does not affect the surgical outcome.

PMID- 25748889
TI  - Double-blind peer review.

PMID- 25748890
TI  - Roche spends $1 billion on Foundation Medicine's tumor profiling.

PMID- 25748892
TI  - $1-million price tag set for Glybera gene therapy.

PMID- 25748895
TI  - Amgen's bispecific antibody puffs across finish line.

PMID- 25748898
TI  - First US biosimilar edges towards market.

PMID- 25748899
TI  - Scotts' GM grass grows free from regulation.

PMID- 25748900
TI  - Next-generation stem cell therapy poised to enter EU market.

PMID- 25748903
TI  - Correction.

PMID- 25748902
TI  - Weight loss 'electroceutical' device wins FDA okay.

PMID- 25748904
TI  - Shire bags NPS, including newly approved biologic for hypoparathyroidism.

PMID- 25748907
TI  - Drugging the gut microbiome.
AB  - Using conventional drug discovery and novel synthetic biology approaches, some
      investigators and companies are mining our resident microbes and their
      metabolites for targets in small-molecule drug programs. Ken Garber reports.

PMID- 25748909
TI  - How to set up collaborations between academia and industrial biotech companies.

PMID- 25748908
TI  - Keys to the kingdom.

PMID- 25748910
TI  - Quality score compression improves genotyping accuracy.

PMID- 25748911
TI  - Ballgown bridges the gap between transcriptome assembly and expression analysis.

PMID- 25748912
TI  - Nature Biotechnology's academic spinouts of 2014.

PMID- 25748913
TI  - Law, history and lessons in the CRISPR patent conflict.

PMID- 25748915
TI  - An integrated microprobe for the brain.

PMID- 25748916
TI  - Singling out blood development.

PMID- 25748917
TI  - Engineering insect-free cereals.

PMID- 25748918
TI  - A systems approach to traditional oriental medicine.

PMID- 25748919
TI  - Total target cash compensation shows a healthy increase at private life-science
      companies.

PMID- 25748922
TI  - Impaired conscious memory in non-clinical schizotypy.
AB  - INTRODUCTION: Impaired controlled and preserved/enhanced automatic memory
      processes have been reported in schizotypy. This memory pattern has been
      considered as a marker of vulnerability to schizophrenia. Our aim was to further
      explore this memory pattern in non-clinical schizotypy in order to determine
      which specific dimensions of schizotypy (i.e., positive, negative or
      disorganised), and more specifically which components of the dimensions, are most
      closely related to memory dysfunctions. METHODS: Fifty-seven undergraduate
      students performed a category-production task. This was adapted for use with the
      process dissociation procedure in order to dissociate between automatic and
      controlled memory processes. The level of schizotypy was assessed using the
      Schizotypal Personality Questionnaire. RESULTS: Regression analyses confirmed
      that controlled memory processes decreased as schizotypy increased. The positive
      factors (more specifically, the ideas of reference subscale) and disorganised
      factors (more specifically, the odd or eccentric behaviour subscale) were
      negatively correlated with the controlled memory processes. CONCLUSIONS: Our
      study supports the idea that impaired controlled processes are an early cognitive
      marker of vulnerability to schizophrenia and confirm that the disorganised factor
      contributes the most to vulnerability to memory dysfunction. It also emphasises
      the importance of dissociating between each of the features characterising
      schizotypy rather than considering it as a whole.

PMID- 25748921
TI  - A high-throughput in vitro drug screen in a genetically engineered mouse model of
      diffuse intrinsic pontine glioma identifies BMS-754807 as a promising therapeutic
      agent.
AB  - Diffuse intrinsic pontine gliomas (DIPGs) represent a particularly lethal type of
      pediatric brain cancer with no effective therapeutic options. Our laboratory has
      previously reported the development of genetically engineered DIPG mouse models
      using the RCAS/tv-a system, including a model driven by PDGF-B, H3.3K27M, and p53
      loss. These models can serve as a platform in which to test novel therapeutics
      prior to the initiation of human clinical trials. In this study, an in vitro high
      throughput drug screen as part of the DIPG preclinical consortium using cell
      lines derived from our DIPG models identified BMS-754807 as a drug of interest in
      DIPG. BMS-754807 is a potent and reversible small molecule multi-kinase inhibitor
      with many targets including IGF-1R, IR, MET, TRKA, TRKB, AURKA, AURKB. In vitro
      evaluation showed significant cytotoxic effects with an IC50 of 0.13 MUM,
      significant inhibition of proliferation at a concentration of 1.5 MUM, as well as
      inhibition of AKT activation. Interestingly, IGF-1R signaling was absent in serum
      free cultures from the PDGF-B; H3.3K27M; p53 deficient model suggesting that the
      antitumor activity of BMS-754807 in this model is independent of IGF-1R. In vivo,
      systemic administration of BMS-754807 to DIPG-bearing mice did not prolong
      survival. Pharmacokinetic analysis demonstrated that tumor tissue drug
      concentrations of BMS-754807 were well below the identified IC50, suggesting that
      inadequate drug delivery may limit in vivo efficacy. In summary, an unbiased in
      vitro drug screen identified BMS-754807 as a potential therapeutic agent in DIPG,
      but BMS-754807 treatment in vivo by systemic delivery did not significantly
      prolong survival of DIPG-bearing mice. 

PMID- 25748923
TI  - Does toxicity of aromatic pollutants increase under remote atmospheric
      conditions?
AB  - Aromatic compounds contribute significantly to the budget of atmospheric
      pollutants and represent considerable hazard to living organisms. However, they
      are only rarely included into atmospheric models which deviate substantially from
      field measurements. A powerful experimental-simulation tool for the assessment of
      the impact of low- and semi-volatile aromatic pollutants on the environment due
      to their atmospheric aqueous phase aging has been developed and introduced for
      the first time. The case study herein reveals that remote biotopes might be the
      most damaged by wet urban guaiacol-containing biomass burning aerosols. It is
      shown that only after the primary pollutant guaiacol has been consumed, its
      probably most toxic nitroaromatic product is largely formed. Revising the recent
      understanding of atmospheric aqueous phase chemistry, which is mostly concerned
      with the radical nitration mechanisms, the observed phenomenon is mainly
      attributed to the electrophilic nitrogen-containing reactive species. Here, their
      intriguing role is closely inspected and discussed from the ecological
      perspective. 

PMID- 25748924
TI  - Review and analysis of existing mobile phone applications for health care
      associated infection prevention.
AB  - BACKGROUND: The expanding number of mobile health applications (apps) holds
      potential to reduce and eliminate health care-associated infections (HAIs) in
      clinical practice. The purpose of this review was to identify and provide an
      overview of the apps available to support prevention of HAIs and to assess their
      functionality and potential uses in clinical care. METHODS: We searched 3 online
      mobile app stores using the following terms: infection prevention, prevention,
      hand hygiene, hand washing, and specific HAI terms (catheter-associated urinary
      tract infection [CAUTI], central line-associated bloodstream infections, surgical
      site infection, and ventilator associated pneumonia [VAP]). RESULTS: Search
      queries yielded a total of 2,646 potentially relevant apps, of which 17 met our
      final inclusion criteria. The areas of focus were CAUTI (n = 1, 5.9%), VAP (n =
      1, 5.9%), environmental monitoring (n = 2, 11.8%), and hand hygiene (n = 2,
      11.8%); the remainder (n = 11, 64.7%) were focused on >1 area (eg, multiple
      infection prevention bundles, infection prevention guidelines). Almost all of the
      apps (70.6%) had a maximum of two functions. CONCLUSION: Mobile apps may help
      reduce HAI by providing easy access to guidelines, hand hygiene monitoring
      support, or step-by-step procedures aimed at reducing infections at the point of
      clinical care. Given the dearth of available apps and the lack of functionality
      with those that are available, there is a need for further development of mobile
      apps for HAI prevention at the point of care.

PMID- 25748925
TI  - Chromosome togetherness at the onset of ESC differentiation.
AB  - Pairing of homologous alleles is a phenomenon generally associated with imprinted
      and mono-allelically expressed loci. In this issue, Hogan et al. (2015) examine
      the earliest steps between pluripotency and lineage commitment in ESCs and find a
      critical role for transient pairing of Oct4 alleles in exiting the pluripotent
      state. 

PMID- 25748926
TI  - Charting a map through the cellular reprogramming landscape.
AB  - Analysis of the molecular mechanisms underlying somatic cell reprogramming into
      iPSCs is hampered by low efficiency of conversion and resulting cellular
      heterogeneity. In this issue of Cell Stem Cell, Zunder et al. (2015) utilize mass
      cytometry to perform high-throughput, single-cell analyses and provide a detailed
      molecular roadmap of the reprogramming process. 

PMID- 25748927
TI  - Confetti clarifies controversy: neural crest stem cells are multipotent.
AB  - Neural crest precursors generate diverse cell lineages during development, which
      have been proposed to arise either from multipotent precursor cells or pools of
      heterogeneous, restricted progenitors. Now in Cell Stem Cell, Baggiolini et al.
      (2015) perform rigorous in vivo lineage tracing to show that individual neural
      crest precursors are multipotent.

PMID- 25748928
TI  - Hostile takeover: glioma stem cells recruit TAMs to support tumor progression.
AB  - The dynamic interaction between cancer cells and immune cells is a critical
      concern for developing effective tumor immunotherapies. In a recent issue of
      Nature Cell Biology, Zhou et al. (2015) report that glioma stem cells secrete
      Periostin (POSTN), which recruits tumor-associated macrophages (TAMs) and
      supports the tumor-promoting M2 subtype. 

PMID- 25748929
TI  - Seven actionable strategies for advancing women in science, engineering, and
      medicine.
AB  - Achieving gender equality in science will require devising and implementing
      strategies to overcome the political, administrative, financial, and cultural
      challenges that exist in the current environment. In this forum, we propose an
      initial shortlist of recommendations to promote gender equality in science and
      stimulate future efforts to level the field. 

PMID- 25748931
TI  - Mesenchymal cell contributions to the stem cell niche.
AB  - Mesenchymal stromal cells (MSCs) are heterogeneous and primitive cells discovered
      first in the bone marrow (BM). They have putative roles in maintaining tissue
      homeostasis and are increasingly recognized as components of stem cell niches,
      which are best defined in the blood. The absence of in vivo MSC markers has
      limited our ability to track their behavior in vivo and draw comparisons with in
      vitro observations. Here we review the historical background of BM-MSCs, advances
      made in their prospective isolation, their developmental origin and contribution
      to maintaining subsets of hematopoietic cells, and how mesenchymal cells
      contribute to other stem cell niches.

PMID- 25748930
TI  - The cancer stem cell niche: how essential is the niche in regulating stemness of
      tumor cells?
AB  - Cancer stem cells (CSCs) are tumor cells that have the principal properties of
      self-renewal, clonal tumor initiation capacity, and clonal long-term repopulation
      potential. CSCs reside in niches, which are anatomically distinct regions within
      the tumor microenvironment. These niches maintain the principle properties of
      CSCs, preserve their phenotypic plasticity, protect them from the immune system,
      and facilitate their metastatic potential. In this perspective, we focus on the
      CSC niche and discuss its contribution to tumor initiation and progression. Since
      CSCs survive many commonly employed cancer therapies, we examine the prospects of
      targeting the niche components as preferable therapeutic targets. 

PMID- 25748932
TI  - Normal and leukemic stem cell niches: insights and therapeutic opportunities.
AB  - Hematopoietic stem cells (HSCs) rely on instructive cues from the bone marrow
      (BM) niche to maintain their quiescence and adapt blood production to the
      organism's needs. Alterations in the BM niche are commonly observed in blood
      malignancies and directly contribute to the aberrant function of disease
      initiating leukemic stem cells (LSCs). Here, we review recent insights into the
      cellular and molecular determinants of the normal HSC niche and describe how
      genetic changes in stromal cells and leukemia-induced BM niche remodeling
      contribute to blood malignancies. Moreover, we discuss how these findings can be
      applied to non-cell-autonomous therapies targeting the LSC niche. 

PMID- 25748933
TI  - Transient pairing of homologous Oct4 alleles accompanies the onset of embryonic
      stem cell differentiation.
AB  - The relationship between chromatin organization and transcriptional regulation is
      an area of intense investigation. We characterized the spatial relationships
      between alleles of the Oct4, Sox2, and Nanog genes in single cells during the
      earliest stages of mouse embryonic stem cell (ESC) differentiation and during
      embryonic development. We describe homologous pairing of the Oct4 alleles during
      ESC differentiation and embryogenesis, and we present evidence that pairing is
      correlated with the kinetics of ESC differentiation. Importantly, we identify
      critical DNA elements within the Oct4 promoter/enhancer region that mediate
      pairing of Oct4 alleles. Finally, we show that mutation of OCT4/SOX2 binding
      sites within this region abolishes inter-chromosomal interactions and affects
      accumulation of the repressive H3K9me2 modification at the Oct4 enhancer. Our
      findings demonstrate that chromatin organization and transcriptional programs are
      intimately connected in ESCs and that the dynamic positioning of the Oct4 alleles
      is associated with the transition from pluripotency to lineage specification. 

PMID- 25748934
TI  - Premigratory and migratory neural crest cells are multipotent in vivo.
AB  - The neural crest (NC) is an embryonic stem/progenitor cell population that
      generates a diverse array of cell lineages, including peripheral neurons,
      myelinating Schwann cells, and melanocytes, among others. However, there is a
      long-standing controversy as to whether this broad developmental perspective
      reflects in vivo multipotency of individual NC cells or whether the NC is
      comprised of a heterogeneous mixture of lineage-restricted progenitors. Here, we
      resolve this controversy by performing in vivo fate mapping of single trunk NC
      cells both at premigratory and migratory stages using the R26R-Confetti mouse
      model. By combining quantitative clonal analyses with definitive markers of
      differentiation, we demonstrate that the vast majority of individual NC cells are
      multipotent, with only few clones contributing to single derivatives.
      Intriguingly, multipotency is maintained in migratory NC cells. Thus, our
      findings provide definitive evidence for the in vivo multipotency of both
      premigratory and migrating NC cells in the mouse. 

PMID- 25748936
TI  - Exploring strategies to operationalize cognitive reserve: A systematic review of
      reviews.
AB  - INTRODUCTION: The cognitive reserve hypothesis suggests that across the lifespan,
      higher education, regular participation in social or mentally stimulating
      activities, and complexity of occupation increase an individual's resistance to
      dementia. However, there is currently no consensus regarding how to assess or
      measure cognitive reserve. METHOD: We performed a systematic review of reviews
      focused on the concept of cognitive reserve to examine key elements of the
      definition and highlight limitations. We searched Embase.com, MEDLINE (OvidSP),
      the Cochrane Library, Web of Science, Scopus, Google Scholar, and PubMed.
      RESULTS: Five systematic reviews were identified. These incorporated findings
      from cohort, cross-sectional, and case-control studies, and the outcomes examined
      included Alzheimer's disease, vascular dementia, nonspecified dementia, all
      dementias, and cognitive decline or cognitive impairment. Education, occupation,
      and leisure or mentally stimulating activities were suggested to supply cognitive
      reserve and offer a protective effect against the risk of dementia. Premorbid IQ
      and socioeconomic status have not been investigated as thoroughly and showed
      inconsistent results. Two of the reviews showed that when combining different
      indicators in the analyses/definition, including education, occupation, mentally
      stimulating activities, and premorbid IQ, cognitive reserve had a protective
      effect against cognitive decline. However, other indicators may also supply the
      reserve, including dietary habits and genetic indicators, but research is lacking
      with regard to creating a full cognitive reserve model. CONCLUSIONS: This review
      highlights the lack of consensus regarding a definition of cognitive reserve.
      Further research is required to clarify how the indicators already identified may
      provide cognitive reserve and offer a protective effect against dementia.
      Agreement on the indicators that constitute the cognitive reserve model is needed
      before testing possible interventions that may increase the reserve supply and
      improve cognition.

PMID- 25748937
TI  - A frontal extramedullary plasmacytoma mimicking parafalcine meningioma.

PMID- 25748935
TI  - A continuous molecular roadmap to iPSC reprogramming through progression analysis
      of single-cell mass cytometry.
AB  - To analyze cellular reprogramming at the single-cell level, mass cytometry was
      used to simultaneously measure markers of pluripotency, differentiation, cell
      cycle status, and cellular signaling throughout the reprogramming process. Time
      resolved progression analysis of the resulting data sets was used to construct a
      continuous molecular roadmap for three independent reprogramming systems.
      Although these systems varied substantially in Oct4, Sox2, Klf4, and c-Myc
      stoichiometry, they presented a common set of reprogramming landmarks. Early in
      the reprogramming process, Oct4(high)Klf4(high) cells transitioned to a
      CD73(high)CD104(high)CD54(low) partially reprogrammed state. Ki67(low) cells from
      this intermediate population reverted to a MEF-like phenotype, but Ki67(high)
      cells advanced through the M-E-T and then bifurcated into two distinct
      populations: an ESC-like Nanog(high)Sox2(high)CD54(high) population and a
      mesendoderm-like Nanog(low)Sox2(low)Lin28(high)CD24(high)PDGFR-alpha(high)
      population. The methods developed here for time-resolved, single-cell progression
      analysis may be used for the study of additional complex and dynamic systems,
      such as cancer progression and embryonic development. 

PMID- 25748938
TI  - Chondromyxoid fibroma of the frontal bone mimicking meningioma.
AB  - Chondromyxoid fibroma (CMF) is a rare benign cartilaginous tumor that usually
      arises from lower-extremity long-bone metaphyses, with approximately 5.4% of all
      CMFs presenting in the craniofacial bones. Chondromyxoid fibroma of the frontal
      bone is exceedingly rare, with only a few cases reported. Herein, we report
      another case of CMF arising from the frontal bone mimicking meningioma. We
      suggest that histopathologic examination is of vital importance for the diagnosis
      of CMF; complete surgical resection is the best treatment option for frontal CMF.

PMID- 25748939
TI  - Treatment of mandibular symphyseal fracture combined with dislocated
      intracapsular condylar fractures.
AB  - OBJECTIVES: To evaluate the treatment methods of mandibular symphyseal fracture
      combined with dislocated intracapsular condylar fractures (MSF&DICF) and to
      compare the effect of different treatment methods of condylar fractures. METHODS:
      Twenty-eight patients with MSF&DICF were included in this study. Twenty-two sites
      were treated by open reduction, and all the medial condylar fragments were fixed
      with titanium screws; whereas the other 22 sites underwent close treatment. The
      surgical effect between these 2 groups was compared based on clinical examination
      and radiographic examination results. RESULTS: Seventeen of 22 condyle fractures
      were repositioned in the surgery group, whereas 4 of 22 condyle fractures were
      repositioned in the close treatment group. Statistical difference was observed
      between these 2 groups (P < 0.01). Functional outcomes of the patients treated in
      the surgical treatment group also were better than those in the close treatment
      group. CONCLUSIONS: The dislocated intracapsular condyle fractures should be
      treated by surgical reduction with the maintenance of the attachment of lateral
      pterygoid muscle, which is beneficial to repositioning the dislocated condyle to
      its original physiological position, to closure of the mandibular lingual gap, to
      restore the mandibular width.

PMID- 25748940
TI  - Temporal bone resorption: an uncommon complication after mandibular distraction.
AB  - Temporal bone absorption is a very infrequent complication following a intraoral
      mandibular distraction. We present a case of severe temporal bone absorption with
      skull base bone destruction in a child who experienced the mandibular distraction
      operation. In her follow-up of the 6th month, it was observed that the implanted
      distraction device drilled to the temporal bone and stretch into the middle
      cranial fossa. We recommend to optimize the positioning of the osteotomy and the
      design of the distraction to avoid the otential risk of adjacent skull
      destruction. 

PMID- 25748941
TI  - Pleomorphic adenoma arising from the palpebral lobe of the lacrimal gland in a
      patient with thyroid-associated ophthalmopathy.
AB  - PURPOSE/BACKGROUND: To report a rare coexistence of pleomorphic adenoma arising
      from the palpebral lobe of the lacrimal gland and thyroid-associated
      ophthalmopathy in a Chinese patient. METHODS: Case report of clinical features
      and imaging findings, orbital surgery, and histopathologic examination. RESULTS:
      A Chinese woman (48 years old) with hyperthyroidism showed a gradually growing
      mass in the lateral region of the left upper eyelid that was present for 4 years
      and bilateral proptosis for 5 years. There was a slightly lower eyelid retraction
      in both eyes. Proptosis was 20 mm in the right eye and 22 mm in the left. A well
      defined, nontender mass was palpable in the lateral upper eyelid of the left eye.
      Ultrasonography and computed tomography revealed a rounded homogenous mass
      measuring 14.1 * 13.2 mm in the lateral upper eyelid of the left eye and enlarged
      superior, medial, and inferior recti muscles in both eyes. At surgery, a grayish
      white round mass was observed after removal of the palpebral lobe of the lacrimal
      gland. The histopathological diagnosis was pleomorphic adenoma of the lacrimal
      gland. CONCLUSIONS: The coexistence of a pleomorphic adenoma of the lacrimal
      gland and thyroid-associated ophthalmopathy may indicate a pleomorphic adenoma
      likely due to an unknown autoimmune disorder.

PMID- 25748942
TI  - Secondary reconstruction for mandibular osteoradionecrosis defect with fibula
      osteomyocutaneous flap flowthrough from radial forearm flap using
      stereolithographic 3-dimensional printing modeling technology.
AB  - Osteoradionecrosis (ORN) is one of the most serious complications of oral and
      nasopharyngeal malignant neoplasms after radiotherapy. The incidence of
      mandibular ORN is significantly higher than that of maxilla. A radical surgical
      intervention such as mandibulectomy for advanced ORN is appropriate and effective
      to relieve pain and control infection. However, recovery of functionality and
      aesthetics is usually not the primary purpose of the one-stage radical surgery.
      Some patients often need a 2-stage operation owing to the bone defect, scar
      contracture, or recurrence. Although free flap has been proven as a reliable way
      to repair the complex maxillofacial defects, it is still a great challenge for
      surgeons to reconstruct the secondary complex mandibular ORN defects. Here, we
      report a case of secondary composite mandibular ORN reconstruction using the
      preoperative 3-dimensional biomodel planning and flowthrough radial forearm flap
      for free fibula osteocutaneous flap. 

PMID- 25748943
TI  - Western Europe, state formation, and genetic pacification.
AB  - Through its monopoly on violence, the State tends to pacify social relations.
      Such pacification proceeded slowly in Western Europe between the 5th and 11th
      centuries, being hindered by the rudimentary nature of law enforcement, the
      belief in a man's right to settle personal disputes as he saw fit, and the
      Church's opposition to the death penalty. These hindrances began to dissolve in
      the 11th century with a consensus by Church and State that the wicked should be
      punished so that the good may live in peace. Courts imposed the death penalty
      more and more often and, by the late Middle Ages, were condemning to death
      between 0.5 and 1.0% of all men of each generation, with perhaps just as many
      offenders dying at the scene of the crime or in prison while awaiting trial.
      Meanwhile, the homicide rate plummeted from the 14th century to the 20th. The
      pool of violent men dried up until most murders occurred under conditions of
      jealousy, intoxication, or extreme stress. The decline in personal violence is
      usually attributed to harsher punishment and the longer-term effects of cultural
      conditioning. It may also be, however, that this new cultural environment
      selected against propensities for violence. 

PMID- 25748944
TI  - In vitro impact of human milk oligosaccharides on Enterobacteriaceae growth.
AB  - Human milk oligosaccharides (HMOs) function as prebiotics in the infant gut by
      selecting for specific species of bifidobacteria and bacteroides, but little is
      known about their potential utilization by Enterobacteriaceae, the relative
      numbers of which have been linked to the onset of necrotizing enterocolitis in
      preterm infants. In this study, the in vitro growth of purified HMOs and other
      related carbohydrates was evaluated using individual strains of
      Enterobacteriaceae and an Enterobacteriaceae consortia enriched from piglet
      feces. None of the Enterobacteriaceae strains grew on 2'-fucosyllactose, 6'
      sialyllactose, or lacto-N-neotetraose (LNnT); however, several strains were
      capable of utilizing galactooligosaccharides, maltodextrin, and the mono- and
      disaccharide components of HMOs for growth. The enriched fecal consortia also did
      not grow on 2'-fucosyllactose or 6'-sialyllactose, but there was limited growth
      on LNnT. It was concluded that 2'-fucosyllactose and 6'-sialyllactose
      supplementation of preterm infant formula should not lead to an increase in
      Enterobacteriaceae; however, supplementation with LNnT may require further study.

PMID- 25748945
TI  - Iridium-bipyridine periodic mesoporous organosilica catalyzed direct C-H
      borylation using a pinacolborane.
AB  - Heterogeneous catalysis for direct C-H borylation of arenes and heteroarenes in
      the combination of iridium (Ir) complex fixed on periodic mesoporous organosilica
      containing bipyridine ligands within the framework (Ir-BPy-PMO) and pinacolborane
      (HBpin) is reported. Ir-BPy-PMO showed higher catalytic activity toward the
      borylation of benzene with inexpensive HBpin compared to expensive
      bis(pinacolato)diboron (B2pin2). The precatalyst could be handled without the use
      of a glove box. The catalyst was easily recovered from reaction mixtures by
      simple filtration under air. The recovered catalyst still showed good catalytic
      activity for at least three more times for the borylation of benzene. A variety
      of arenes and heteroarenes were successfully borylated with high boron efficiency
      by Ir-BPy-PMO using HBpin, whereas almost no activity was observed for borylation
      of some heteroarenes with B2pin2. The system using Ir-BPy-PMO and HBpin was also
      utilized in syntheses of multi-boronated thiophene-based building blocks
      containing ladder-, acenefused-, and fused-thiophene skeletons. The combination
      of a stable and reusable solid catalyst and inexpensive HBpin is expected to be
      superior to conventional approaches for the development of industrial
      applications. 

PMID- 25748946
TI  - Correction to "Avenaciolides: potential MurA-targeted inhibitors against
      peptidoglycan biosynthesis in methicillin-resistant Staphylococcus aureus
      (MRSA)".

PMID- 25748947
TI  - Potential parasite transmission in multi-host networks based on parasite sharing.
AB  - Epidemiological networks are commonly used to explore dynamics of parasite
      transmission among individuals in a population of a given host species. However,
      many parasites infect multiple host species, and thus multi-host networks may
      offer a better framework for investigating parasite dynamics. We investigated the
      factors that influence parasite sharing--and thus potential transmission pathways
      -among rodent hosts in Southeast Asia. We focused on differences between networks
      of a single host species and networks that involve multiple host species. In host
      parasite networks, modularity (the extent to which the network is divided into
      subgroups of rodents that interact with similar parasites) was higher in the
      multi-species than in the single-species networks. This suggests that phylogeny
      affects patterns of parasite sharing, which was confirmed in analyses showing
      that it predicted affiliation of individuals to modules. We then constructed
      "potential transmission networks" based on the host-parasite networks, in which
      edges depict the similarity between a pair of individuals in the parasites they
      share. The centrality of individuals in these networks differed between multi-
      and single-species networks, with species identity and individual characteristics
      influencing their position in the networks. Simulations further revealed that
      parasite dynamics differed between multi- and single-species networks. We
      conclude that multi-host networks based on parasite sharing can provide new
      insights into the potential for transmission among hosts in an ecological
      community. In addition, the factors that determine the nature of parasite sharing
      (i.e. structure of the host-parasite network) may impact transmission patterns.

PMID- 25748948
TI  - Poor transferability of species distribution models for a pelagic predator, the
      grey petrel, indicates contrasting habitat preferences across ocean basins.
AB  - Species distribution models (SDMs) are increasingly applied in conservation
      management to predict suitable habitat for poorly known populations. High
      predictive performance of SDMs is evident in validations performed within the
      model calibration area (interpolation), but few studies have assessed SDM
      transferability to novel areas (extrapolation), particularly across large spatial
      scales or pelagic ecosystems. We performed rigorous SDM validation tests on
      distribution data from three populations of a long-ranging marine predator, the
      grey petrel Procellaria cinerea, to assess model transferability across the
      Southern Hemisphere (25-65 degrees S). Oceanographic data were combined with
      tracks of grey petrels from two remote sub-Antarctic islands (Antipodes and
      Kerguelen) using boosted regression trees to generate three SDMs: one for each
      island population, and a combined model. The predictive performance of these
      models was assessed using withheld tracking data from within the model
      calibration areas (interpolation), and from a third population, Marion Island
      (extrapolation). Predictive performance was assessed using k-fold cross
      validation and point biserial correlation. The two population-specific SDMs
      included the same predictor variables and suggested birds responded to the same
      broad-scale oceanographic influences. However, all model validation tests,
      including of the combined model, determined strong interpolation but weak
      extrapolation capabilities. These results indicate that habitat use reflects both
      its availability and bird preferences, such that the realized distribution
      patterns differ for each population. The spatial predictions by the three SDMs
      were compared with tracking data and fishing effort to demonstrate the
      conservation pitfalls of extrapolating SDMs outside calibration regions. This
      exercise revealed that SDM predictions would have led to an underestimate of
      overlap with fishing effort and potentially misinformed bycatch mitigation
      efforts. Although SDMs can elucidate potential distribution patterns relative to
      large-scale climatic and oceanographic conditions, knowledge of local habitat
      availability and preferences is necessary to understand and successfully predict
      region-specific realized distribution patterns. 

PMID- 25748949
TI  - The Revised Formal Social Support for Autonomy and Dependence in Pain Inventory
      (FSSADI_PAIN): Confirmatory Factor Analysis and Validity.
AB  - Pain among older adults is common and generally associated with high levels of
      functional disability. Despite its important role in elders' pain experiences,
      perceived (formal) social support (PSS) has shown inconsistent effects on their
      functional autonomy. This suggests a moderator role of 2 recently conceptualized
      functions of PSS: perceived promotion of dependence versus autonomy. The present
      study aimed at revising and further validating the Formal Social Support for
      Autonomy and Dependence in Pain Inventory (FSSADI_PAIN), which measures these 2
      PSS functions among institutionalized elders in pain. Two hundred fifty older
      adults (mean age = 81.36 years, 75.2% women) completed the revised FSSADI_PAIN
      along with measures of physical functioning (ie, Medical Outcome Study Short Form
      36) and informal PSS (ie, Social Support Scale of Medical Outcomes Study).
      Confirmatory factor analyses showed a good fit for a 2-factor structure: 1)
      perceived promotion of autonomy (n = 4 items; alpha = .89), and 2) perceived
      promotion of dependence (n = 4 items; alpha = .85). The revised FSSADI_PAIN
      showed good content, discriminant, and criterion-related validity; it
      discriminated the PSS of male and female older adults and also of elders with
      different levels of physical functioning. In conclusion, the revised FSSADI_PAIN
      is an innovative, valid, and reliable tool that allows us to assess 2 important
      functions of PSS, which may play a relevant role in the prevention and reduction
      of pain-related physical disability and functional dependence among
      institutionalized older adults. PERSPECTIVE: This article presents a revised
      version of the FSSADI_PAIN that assesses elders' perceived promotion of
      functional autonomy/dependence as 2 independent functions of perceived social
      support. This measure may contribute to future research on the role of close
      interpersonal contexts on the promotion of active aging among elders with chronic
      pain.

PMID- 25748950
TI  - Association between the PPARGC1A polymorphism and aerobic capacity in Japanese
      middle-aged men.
AB  - OBJECTIVE: A lower frequency for the peroxisome proliferator-activated receptor
      gamma coactivator 1alpha (PPARGC1A) Ser482 allele has been reported in elite
      level endurance athletes among Caucasians, although this gene polymorphism has
      not been found to be associated with aerobic capacity in German, Dutch or Chinese
      populations. The purpose of the current study was to examine the associations
      between the Gly482Ser polymorphism and aerobic fitness in 112 Japanese middle
      aged men. METHODS: The PPARGC1A Gly482Ser polymorphism was identified according
      to a TaqMan((r)) SNP genotyping assay. Habitual physical activity was objectively
      measured using an accelerometer. The lactate threshold (LT), an index of aerobic
      fitness, was measured based on a submaximal graded exercise test performed on an
      electric cycle ergometer. The association between the LT and the Gly482Ser
      polymorphism was assessed according to a multiple regression analysis and
      analysis of covariance, with adjustment for potential confounders (age, body mass
      index, cigarette smoking, physical activity level and regular exercise). RESULTS:
      A significant association was observed between the PPARGC1A Gly482Ser
      polymorphism and LT, as carriers of the Ser482 had higher LT values than the
      Gly482 carriers. CONCLUSION: The current results suggest that the PPARGC1A Ser482
      allele is associated with a higher aerobic capacity in Japanese middle-aged men.

PMID- 25748951
TI  - Evaluation of myocardial triglyceride accumulation assessed on 1H-magnetic
      resonance spectroscopy in apparently healthy Japanese subjects.
AB  - OBJECTIVE: Proton magnetic resonance spectroscopy ((1)H-MRS) enables the
      clinician to noninvasively assess the amount of ectopic fat in the liver,
      skeletal muscle and myocardium. Recent studies have reported that the myocardial
      triglyceride (TG) content is associated with aging, metabolic disorders and
      cardiac dysfunction. However, the clinical usefulness of myocardial TG
      measurements in Japanese subjects has not been fully investigated. METHODS: The
      myocardial TG content was evaluated using (1)H-MRS in 37 apparently healthy
      Japanese subjects, and the left ventricular function was measured on cardiac
      magnetic resonance imaging (MRI). Blood pressure, body composition and
      biochemical markers were measured in a fasting state, and cardiopulmonary
      exercise testing (CPX) was performed to evaluate exercise capacity. RESULTS: The
      mean myocardial TG content was 0.85+/-0.40%. The myocardial TG content was
      significantly associated with the percent body fat (r=0.39), serum triglyceride
      level (r=0.40), estimated glomerular filtration rate (r=-0.37), anaerobic
      threshold (r=-0.36), maximal load of CPX (r=0.39), left ventricular end-diastolic
      volume (r=-0.41) and left ventricular end-systolic volume (LVESV) (r=-0.51) (all:
      p<0.05). In a multivariate analysis, the LVESV was found to be an independent
      factor of the myocardial TG content. CONCLUSION: (1)H-MRS may be useful for
      assessing the associations between the myocardial TG content and various clinical
      parameters, including those reflecting obesity, metabolic disorders, cardiac
      morphology and exercise capacity, noninvasively, even in Japanese subjects.

PMID- 25748952
TI  - Risk of chronic kidney disease in non-obese individuals with clustering of
      metabolic factors: a longitudinal study.
AB  - OBJECTIVE: The impact of the clustering of metabolic factors on chronic kidney
      disease (CKD) in non-obese individuals remains unclear. METHODS: We conducted a
      follow-up study of 23,894 Japanese adults (age, 18-69 years) who continuously
      received annual health examinations between 2000 and 2011. Obesity, high blood
      pressure, high triglycerides, low high-density lipoprotein (HDL) cholesterol and
      high fasting blood sugar were defined as metabolic factors, and CKD was defined
      as renal dysfunction (estimated glomerular filtration rate: <60 mL/min/1.73 m(2))
      or proteinuria (dipstick test: >=1+). The association between the clustering of
      metabolic factors and CKD was assessed based on the presence or absence of
      obesity using a Cox proportional hazard model. RESULTS: Of 2,867 subjects with
      >=3 metabolic factors, 650 (22.7%) were non-obese. These individuals were older
      and had higher metabolic risks than their obese counterparts at baseline. Among
      the entire cohort of 23,894 subjects, 1,764 developed renal dysfunction and 904
      developed proteinuria during an average follow-up period of 7.8 years. The
      cumulative incidence of renal dysfunction was higher (22.1% vs. 16.1%), whereas
      that of proteinuria was lower (10.5% vs. 14.4%), among the non-obese subjects
      with >=3 metabolic factors than the obese subjects with >=3 metabolic factors
      after 11 years. The adjusted relative risk (RR) (95% confidence interval) of
      renal dysfunction was 1.54 (1.34-1.77) and 1.67 (1.35-2.07) for the obese and non
      obese subjects with >=3 metabolic factors, respectively. CONCLUSION: Non-obese
      subjects with >=3 metabolic factors, who are missed based on the essential
      criterion of obesity for metabolic syndrome, may have an equal or slightly higher
      risk of renal dysfunction than obese subjects with >=3 metabolic factors.

PMID- 25748953
TI  - Development of nodular regenerative hyperplasia (NRH) with portal hypertension
      following the administration of oxaliplatin for the recurrence of colon cancer.
AB  - Nodular regenerative hyperplasia (NRH) is associated with autoimmune and
      hematologic diseases and may lead to portal hypertension. We herein report a case
      of NRH diagnosed based on a liver biopsy. A 63-year-old woman developed
      esophageal varices and splenomegaly. She had undergone surgery for transverse
      colon cancer 24 years earlier and received systemic chemotherapy (FOLFOX4
      including oxaliplatin) to treat lymph node metastasis 21 years after the
      operation. The present liver biopsy confirmed NRH, and, after two years, she
      received endoscopic injection sclerotherapy. Oxaliplatin was suspected to be the
      causative agent of NRH in this case. Therefore, physicians must consider the
      possibility of NRH in patients who receive chemotherapy. 

PMID- 25748954
TI  - Hepatic peribiliary cysts with rapidly progressive refractory obstructive
      jaundice and esophageal varices.
AB  - A 54-year-old man with decompensated alcoholic liver cirrhosis presented with
      acute cholangitis. Although no localized lesions were detected in the liver on
      contrast-enhanced computed tomography and no risky varices were noted on
      endoscopy, hepatic peribiliary cysts (HPBCs) developed along the intrahepatic
      portal vein in the course of only 40 days. Moreover, esophageal varices with the
      red color sign grew rapidly during the same period, and the patient ultimately
      died due to rupture. HPBC formation is a rare complication of liver disease,
      including cirrhosis. Although HPBCs are generally harmless, on rare occasions
      they may induce the rapid progression of esophageal varices. 

PMID- 25748955
TI  - Drug-induced liver injury with serious multiform exudative erythema following the
      use of an over-the-counter medication containing ibuprofen.
AB  - A 36-year-old Japanese woman took over-the-counter (OTC) medication for headaches
      for 20 days. Subsequently, five days after discontinuing the medication, a skin
      rash developed over the patient's upper and lower limbs and face, in addition to
      a fever, brown urine and serious liver dysfunction. Drug lymphocyte stimulation
      tests implicated ibuprofen, a main component of the OTC drugs, which has the
      potential to induce this pathology, and a diagnosis of drug-induced liver injury
      with multiform exudative erythema was made. The patient's symptoms and liver
      function tests returned to normal following treatment with systemic steroids. 

PMID- 25748956
TI  - Methotrexate-related primary hepatic lymphoma in a patient with rheumatoid
      arthritis.
AB  - A 56-year-old woman with rheumatoid arthritis treated with methotrexate (MTX) was
      admitted to our hospital due to multiple liver tumors. Contrast-enhanced computed
      tomography (CT) revealed multiple hypovascular masses, and 18F-fluorodeoxyglucose
      positron emission tomography CT showed diffuse abnormal accumulation in the liver
      only. We therefore made a diagnosis of MTX-related primary hepatic lymphoma (MTX
      PHL) exhibiting features of diffuse large B-cell lymphoma. Although MTX has been
      reported to increase the risk of lymphoproliferative disorders, MTX-PHL has not
      been reported previously. The present case is the first case in which MTX appears
      to have been involved in the development of PHL. 

PMID- 25748957
TI  - Clear visualization of extravasation on angiography using carbon dioxide in a
      case of hepatocellular carcinoma rupture with unclear visualization using iodine
      contrast agent.
AB  - A 62-year-old woman with hepatocellular carcinoma (HCC) and asthma presented with
      acute abdominal pain and a decreased hemoglobin level. Peritoneal fluid was
      detected around the lesion, and rupture was suspected based on the findings of
      computed tomography. Extravasation of the HCC tumor was not detected on
      angiography with iodine contrast agent; however, such extravasation was clearly
      observed on angiography with carbon dioxide (CO2). CO2 angiography is sometimes
      utilized in patients with arterial bleeding. This modality be more effective and
      safe than angiography with iodine contrast agent for assessing potential ruptured
      HCC lesions. 

PMID- 25748958
TI  - Early surgical intervention and optimal medical treatment for Candida
      parapsilosis endocarditis.
AB  - We herein report the case of a 72-year-old man with endocarditis of the aortic
      valve who underwent urgent aortic valve replacement 36 hours after admission due
      to an aggravation of aortic valve regurgitation. Postoperative cultures of the
      blood and site of valve vegetation identified Candida parapsilosis as a pathogen.
      Antifungal therapy with amphotericin B and fluconazole was initiated after
      surgical treatment. Thereafter, the patient displayed a favorable clinical
      course. Candida parapsilosis endocarditis involving the native valves is
      extremely rare and associated with a very high mortality rate. Prompt surgical
      treatment and the aggressive use of antifungal agents are required to save the
      patient's life. 

PMID- 25748959
TI  - Primary aldosteronism presenting with an atypical aldosterone-renin ratio in the
      acute phase of cerebral hemorrhage.
AB  - The aldosterone-renin ratio (ARR) is considered to be the most reliable and
      sensitive screening parameter for primary aldosteronism (PA). However, little is
      known regarding how stroke influences the ARR. We herein present a case of a 35
      year-old man who was ultimately found to have PA after diagnostic challenges. The
      patient showed an atypical ARR in the acute phase of cerebral hemorrhage. We
      therefore conclude that the ARR may be inappropriately decreased immediately
      after stroke in patients with PA, presumably due to sympathetic activation and
      the effects of medications. When diagnosing PA in patients with stroke, we
      suggest reevaluating the ARR in the stable phase. 

PMID- 25748960
TI  - Onset of reversible flaccid quadriplegia during treatment of thyrotoxic crisis.
AB  - Two unrelated women were hospitalized for thyrotoxic crisis complicated by
      multiple organ failure. Both patients were treated with antithyroid drugs and
      hydrocortisone, as well as insulin for hyperglycemia, and underwent mechanical
      ventilation with sedation. Flaccid quadriplegia became apparent after each
      patient completely recovered their level of consciousness once sedation was
      discontinued on days 6 and 15, respectively. Three to six months of
      rehabilitation was required for the muscle strength to fully improve in both
      cases. Thyrotoxicosis in addition to critical illness polyneuromyopathy and the
      administration of glucocorticoid therapy may have contributed to the onset of
      quadriplegia in these two cases. Flaccid quadriplegia is one of the serious
      neuromuscular conditions experienced during the treatment of thyrotoxic crisis. 

PMID- 25748961
TI  - Partially thrombosed vertebral artery dissecting aneurysm presenting as delayed
      bulbar compression after lateral medullary infarction.
AB  - A 48-year-old man experienced lateral medullary infarction resulting from
      spontaneous vertebral artery (VA) dissection. Minimal fusiform dilatation was
      noted on basi-parallel anatomic scanning-magnetic resonance imaging; therefore,
      the patient was treated conservatively. Eight months later, he experienced
      deterioration of dysphagia and the onset of gait ataxia. Repeated imaging studies
      showed enlargement of the VA aneurysm with bulbar compression. Parent artery
      occlusion on the proximal side of the VA affected by the dissection relieved the
      patient's symptoms. Although the majority of dissected lesions stabilize within a
      few months, studies with longer observation periods and more frequent
      neuroimaging examinations are required. 

PMID- 25748962
TI  - Ankylosing spondylitis associated with pulmonary arterial hypertension.
AB  - Pulmonary arterial hypertension (PAH) is a frequent complication of connective
      tissue diseases, such as systemic sclerosis, systemic lupus erythematosus and
      rheumatoid arthritis. However, the occurrence of PAH in a patient with ankylosing
      spondylitis (AS) has not been previously reported with a detailed clinical
      description in the English literature. We herein report the first case of AS
      associated PAH in a 27-year-old Taiwanese man with a chief complaint of
      intermittent palpitations lasting for two years. To the best of our knowledge,
      this is the first reported case of AS associated with PAH with a detailed
      clinical description and findings of right heart catheterization published in the
      English literature. 

PMID- 25748963
TI  - Successful treatment of cardiac lymphoma.

PMID- 25748964
TI  - Mesenteric cavernous hemangioma with urological symptoms.

PMID- 25748965
TI  - Diagnostic accuracy of diffusion MRI with quantitative ADC measurements in
      differentiating glioma recurrence from radiation necrosis.
AB  - OBJECTIVE: Differentiating radiation necrosis from glioma recurrence remains a
      great challenge. Several advanced imaging modalities have been developed to
      differentiate between these two entities with disparate outcomes. We conducted a
      meta-analysis to evaluate the diagnostic quality of diffusion MRI in
      differentiating glioma recurrence from radiation necrosis. METHOD: PubMed, Embase
      and Chinese Biomedical databases were systematically searched to identify
      published articles about evaluation of diffusion MRI for the differential
      diagnosis of glioma recurrence from radiation necrosis. Pooled sensitivity (SEN),
      specificity (SPE), negative likelihood ratio (NLR), positive likelihood ratio
      (PLR), and diagnostic odds ratio (DOR) were calculated. RESULTS: Nine studies
      involving 284 patients (288 lesions) met all inclusion and exclusion criteria.
      Quantitative synthesis of studies showed that the pooled weighted values were
      determined to be SEN: 0.82 (95% CI: 0.75, 0.87); SPE: 0.84 (95% CI: 0.76, 0.91);
      PLR: 5.10 (95% CI: 3.27, 7.95); NLR: 0.21 (95% CI: 0.15, 0.29); and DOR: 23.90
      (95% CI: 12.44, 45.89). CONCLUSIONS: This meta-analysis shows that diffusion MRI
      has moderate diagnostic performance in differentiating glioma recurrence from
      radiation necrosis using quantitative ADC. It is recommended not to use diffusion
      MRI alone in differentiating between glioma recurrence and radiation necrosis.
      Multimodal imaging trials should be implemented in the future.

PMID- 25748966
TI  - Fatigue in patients with multiple sclerosis: from movement preparation to motor
      execution.
AB  - BACKGROUND: The neural mechanisms underlying fatigue in multiple sclerosis (MS)
      are still poorly understood. Cortico-cortical and cortico-subcortical circuitry
      abnormalities may play a central role in its pathogenesis. Our previous studies
      suggest that central fatigue may be related to an impairment of volition drive
      during movement preparation. OBJECTIVE: We further explored the central
      mechanisms of fatigue at the premovement level in MS patients during a sustained
      motor task. METHODS: In MS patients with (MS-F) and without (MS-NF) fatigue and
      age-matched healthy controls, we evaluated the motor cortex excitability and the
      premovement facilitation (PMF) through transcranial magnetic stimulation before
      and after 5min of sequenced finger-tapping movements at a fixed frequency of 2Hz.
      RESULTS: In MS-F patients, the number of correct sequences performed and the
      ability to keep a fixed movement rate during the 5-min motor task were
      significantly decreased in comparison to the normal controls and MS-NF patients.
      Also, in MS-F patients, post-exercise PMF was significantly decreased. The PMF
      abnormalities were highly correlated with the performance decay. CONCLUSIONS: PMF
      may be considered as a kind of servo-mechanism which could play a crucial role
      during sustained motor task in order to prevent motor performance disruption and
      to avoid motor exhaustion.

PMID- 25748967
TI  - Methylphenidate prolongs symptom-free period of experimental prion disease in
      mice.

PMID- 25748968
TI  - Elderly and forgetful with transient neurological spells: a story of two
      amyloids?

PMID- 25748969
TI  - Satisfaction and perceived quality of life results in patients operated on for
      primary hernia of the abdominal wall.
AB  - INTRODUCTION: Outpatient surgery is currently the standard procedure in 60-70% of
      the most prevalent surgical procedures. Minimally invasive models in health care
      have improved basic aspects such as postoperative pain and hospital stay, but
      there are few publications related to perceived quality shown by patients, such
      as the need for informal care at home or delay before surgery. The aim of the
      study was to determine the global satisfaction perceived by patients undergoing
      abdominal wall hernia repair. METHODS: An ad hoc split questionnaire has been
      completed on satisfaction after a week and postoperative quality a month after
      intervention by 203 patients operated on for abdominal hernia in a year.
      Variables included postoperative pain, need for informal care, surgical delay,
      information supplied, professional management and overall satisfaction. RESULTS:
      A total of 48.28% of patients needed informal care at home. They were largely
      attended by women, wives or daughters, for a few days. In 45.81% they were
      discharged on the same day, and 53.2% in less than 72 h. Overall satisfaction in
      the program of day surgery and short hospital stay was 94.6%. CONCLUSIONS: The
      overall process of satisfaction was not related to age, sex or educational level
      of patients, while there was an inverse relationship between satisfaction and
      days of hospitalization and days of pain that required analgesia at home.

PMID- 25748972
TI  - Outside looking in, inside looking out--expanding the concept of health.

PMID- 25748970
TI  - Molecular basis of chromatic adaptation in pennate diatom Phaeodactylum
      tricornutum.
AB  - The remarkable adaptability of diatoms living in a highly variable environment
      assures their prominence among marine primary producers. The present study
      integrates biochemical, biophysical and genomic data to bring new insights into
      the molecular mechanism of chromatic adaptation of pennate diatoms in model
      species Phaeodactylum tricornutum, a marine eukaryote alga possessing the
      capability to shift its absorption up to ~700 nm as a consequence of incident
      light enhanced in the red component. Presence of these low energy spectral forms
      of Chl a is manifested by room temperature fluorescence emission maximum at 710
      nm (F710). Here we report a successful isolation of the supramolecular protein
      complex emitting F710 and identify a member of the Fucoxanthin Chlorophyll a/c
      binding Protein family, Lhcf15, as its key building block. This red-shifted
      antenna complex of P. tricornutum appears to be functionally connected to
      photosystem II. Phylogenetic analyses do not support relation of Lhcf15 of P.
      tricornutum to other known red-shifted antenna proteins thus indicating a case of
      convergent evolutionary adaptation towards survival in shaded environments.

PMID- 25748971
TI  - Reconsidering "inattention" in attention-deficit hyperactivity disorder:
      implications for neuropsychological assessment and intervention.
AB  - Attention-deficit hyperactivity disorder (ADHD) does not exist. This explicit
      statement needs elucidation of course given ADHD is a common neurodevelopmental
      disorder, but it provides the reader with the impetus to reconsider long-held
      beliefs about this condition and its treatment. Surely, there is a disorder
      called ADHD from which this thesis is framed, but primary attention and
      hyperactivity-impulsivity problems are mediated by different albeit interrelated
      brain systems. Like many neurodevelopmental disorders (e.g., learning
      disabilities, autism spectrum disorder), the medical and psychological
      professions have used a single, large inclusive ADHD diagnostic category to
      represent children with different etiologies for their overt symptoms. Despite
      neurobiological differences among children diagnosed with ADHD, the clinical
      position that attention-deficit or primary attention problems are sufficient for
      ADHD identification undermines clinical practice. This commonly accepted dubious
      position not only undermines the diagnostic utility of our neuropsychological
      measures, but it attenuates treatment effects as well. Supported with evidence
      from our ongoing ADHD research program, this data-based review will support these
      contentions and provide implications for diagnosis and treatment of children with
      attention problems. 

PMID- 25748973
TI  - Simulation-based medical education in pediatrics.
AB  - The use of simulation-based medical education (SBME) in pediatrics has grown
      rapidly over the past 2 decades and is expected to continue to grow. Similar to
      other instructional formats used in medical education, SBME is an instructional
      methodology that facilitates learning. Successful use of SBME in pediatrics
      requires attention to basic educational principles, including the incorporation
      of clear learning objectives. To facilitate learning during simulation the
      psychological safety of the participants must be ensured, and when done
      correctly, SBME is a powerful tool to enhance patient safety in pediatrics. Here
      we provide an overview of SBME in pediatrics and review key topics in the field.
      We first review the tools of the trade and examine various types of simulators
      used in pediatric SBME, including human patient simulators, task trainers,
      standardized patients, and virtual reality simulation. Then we explore several
      uses of simulation that have been shown to lead to effective learning, including
      curriculum integration, feedback and debriefing, deliberate practice, mastery
      learning, and range of difficulty and clinical variation. Examples of how these
      practices have been successfully used in pediatrics are provided. Finally, we
      discuss the future of pediatric SBME. As a community, pediatric simulation
      educators and researchers have been a leading force in the advancement of
      simulation in medicine. As the use of SBME in pediatrics expands, we hope this
      perspective will serve as a guide for those interested in improving the state of
      pediatric SBME. 

PMID- 25748974
TI  - Developing leaders in pediatric graduate medical education: the APPD LEAD
      Program.

PMID- 25748975
TI  - Lucky.

PMID- 25748976
TI  - Effect of provider prompts on adolescent immunization rates: a randomized trial.
AB  - OBJECTIVE: Adolescent immunization rates are suboptimal. Experts recommend
      provider prompts at health care visits to improve rates. We assessed the impact
      of either electronic health record (EHR) or nurse- or staff-initiated provider
      prompts on adolescent immunization rates. METHODS: We conducted a randomized
      controlled trial, allocating practices in 1 of 2 practice-based research networks
      (PBRN) to provider prompts or standard-of-care control. Ten primary care
      practices participated, 5 intervention and 5 controls, each matched in pairs on
      urban, suburban, or rural location and practice type (pediatric or family
      medicine), from a PBRN in Greater Rochester, New York (GR-PBRN); and 12
      practices, 6 intervention, 6 controls, similarly matched, from a national
      pediatric continuity clinic PBRN (CORNET). The study period was 1 year per
      practice, ranging from June 2011 to January 2013. Study participants were
      adolescents 11 to 17 years attending these 22 practices; random sample of chart
      reviews per practice for baseline and postintervention year to assess
      immunization rates (n = 7,040 total chart reviews for adolescents with >1 visit
      in a period). The intervention was an EHR prompt (4 GR-PBRN and 5 CORNET practice
      pairs) (alert) that appeared on providers' computer screens at all office visits,
      indicating the specific immunizations that adolescents were recommended to
      receive. Staff prompts (1 GR-PBRN pair and 1 CORNET pair) in the form of a
      reminder sheet was placed on the provider's desk in the exam room indicating the
      vaccines due. We compared immunization rates, stratified by PBRN, for routine
      vaccines (meningococcus, pertussis, human papillomavirus, influenza) at study
      beginning and end. RESULTS: Intervention and control practices within each PBRN
      were similar at baseline for demographics and immunization rates. Immunization
      rates at the study end for adolescents who were behind on immunizations at study
      initiation were not significantly different for intervention versus control
      practices for any vaccine or combination of vaccines. Results were similar for
      each PBRN and also when only EHR-based prompts was assessed. For example, at
      study end, 3-dose human papillomavirus vaccination rates for GR-PBRN intervention
      versus control practices were 51% versus 53% (adjusted odds ratio 0.96; 95%
      confidence interval 0.64-1.34); CORNET intervention versus control rates were 50%
      versus 42% (adjusted odds ratio 1.06; 95% confidence interval 0.68-1.88).
      CONCLUSIONS AND RELEVANCE: In both a local and national setting, provider prompts
      failed to improve adolescent immunization rates. More rigorous practice-based
      changes are needed.

PMID- 25748978
TI  - Sweet Syndrome After Autologous Stem Cell Transplant.
AB  - Sweet syndrome (acute febrile neutrophilic dermatosis) is a rare clinical entity
      characterized by skin lesions, neutrophilia, fever, and neutrophilic infiltration
      of the dermis. It may be a consequence of malignant disease, comorbidities, or
      drugs. We present a case of acute febrile neutrophilic dermatosis in a patient
      after autologous stem cell transplant.

PMID- 25748977
TI  - Family-based obesity treatment in children with disabilities.
AB  - OBJECTIVE: To assess the relative effectiveness of an interdisciplinary, family
      centered, tertiary-care pediatric weight management program for the treatment of
      patients with and without cognitive disabilities (CD). METHODS: Retrospective
      analysis of the clinical database of a tertiary-care pediatric weight management
      clinic (n = 453), extracting data from electronic health records including
      longitudinal change in weight status (body mass index [BMI] z-score) and
      frequency of attrition from treatment. Upon review of medical records, children
      enrolled in the treatment program were classified as having no CD (n = 342) or CD
      (n = 111). RESULTS: At baseline, there were no between-group differences in BMI
      or BMI z-score. After 4 months of treatment, 66% (299) of patients remained
      enrolled, and complete case data were available for 219 children in final
      analyses. There were no statistically significant differences in attrition
      between the 2 groups (no CD vs CD). Mean change in BMI z-score across all groups
      was -0.03 +/- 0.13 (P < .001). Change in BMI z-score was significantly greater
      among patients with CD (-0.07 +/- 0.15) compared to those without CD (-0.03 +/-
      0.12) (difference 0.04, 95% confidence interval 0.005-0.08, P = .029). These
      change estimates were observed after adjusting for processes potentially
      associated with attrition. CONCLUSIONS: Children with CD treated in an
      interdisciplinary, family-centered obesity clinic had similar or better outcomes
      compared to peers without CD. This success may be attributable to the patient
      centered nature of this behavioral weight management program, which focused on
      leveraging the unique strengths and capabilities of each individual patient and
      family.

PMID- 25748979
TI  - [Inhibition of aflatoxin production and fungal growth on stored corn by allyl
      isothiocyanate vapor].
AB  - Studies were conducted to determine the effectiveness of allyl isothiocyanate
      (AIT) vapor treatment with a commercial mustard seed extract (Wasaouro((r))) in
      controlling aflatoxin-producing fungi on stored corn. The concentration of AIT in
      the closed container peaked at 54.6 ng/mL on the 14th day and remained at 21.8
      ng/mL on the 42nd day. AIT inhibited visible growth of aflatoxigenic molds in
      unsterilized corn and in sterilized corn inoculated with various aflatoxigenic
      fungi. However, fungi such as Aspergillus glaucus group, A. penicillioides and A.
      restrictus were detected by means of culture methods. 

PMID- 25748980
TI  - [Analysis of colorants in foods using liquid chromatography-mass spectrometry].
AB  - A method using liquid chromatography coupled with mass spectrometry (LC-MS) was
      developed for the simultaneous determination of colorants in foods. Twenty-five
      colorants were extracted from foods with water or methanol and ammonia water, and
      cleaned up with a solid-phase extraction column. Recovery rates were between 71
      and 113%, and relative standard deviations were less than 10%. The detection
      limits of the colorants were 0.2-0.8 MUg/g. The analytical method using LC-MS
      established in this study is suitable for the detection of colorants in processed
      foods. 

PMID- 25748981
TI  - [Determination method of ultra-high-intensity sweetener, advantame, in processed
      foods by HPLC and LC-MS/MS].
AB  - A simple method using HPLC and LC-MS/MS was developed for the determination of
      ultra-high-intensity sweetener, advantame, in processed foods. Advantame was
      extracted by dialysis, and cleaned up on a Sep-Pak Plus C18 cartridge, then
      determined by HPLC and LC-MS/MS. The recoveries from 5 kinds of processed foods
      fortified at the levels of 0.001 g/kg and 0.01 g/kg were 64.1-89.9% (RSD 0.9
      6.9%) by HPLC and 68.8-99.9% (RSD 0.8-4.9%) by LC-MS/MS. The quantitation limit
      was 0.0004 g/kg by HPLC and 0.00004 g/kg by LC-MS/MS. 

PMID- 25748982
TI  - [Single-laboratory validation study of simple and simultaneous determination
      method for pesticide residues in meat by LC-MS/MS].
AB  - We performed a single-laboratory validation study of a simple and simultaneous
      determination method for pesticide residues in meat using LC-MS/MS. Water was
      added to the sample and the mixture was homogenized. Next, pesticides were
      extracted with acetonitrile containing 1 vol% formic acid using a homogenizer,
      and salted out with magnesium sulfate, trisodium citrate and sodium chloride.
      After centrifugation, the acetonitrile layer was made up to standard volume and
      analyzed by LC-MS/MS. This method was assessed by performing recovery tests in
      retail bovine, swine and chicken muscle samples spiked with the 132 pesticides at
      the levels of 0.01 and 0.04 MUg/g. Among them, 125 pesticides satisfied the
      Japanese method validation guideline criteria in bovine, 120 in swine and 127 in
      chicken. 

PMID- 25748983
TI  - [Validation study of analysis of Malachite green in broiled eels (Kabayaki) by LC
      MS/MS].
AB  - An improved method for analysis of Malachite green (MG) and its metabolite,
      Leucomalachite green (LMG), in broiled eels without using dichloromethane was
      developed. This method was evaluated by means of recovery tests according to the
      guideline for validation of analytical methods by the Ministry of Health, Labour
      and Welfare of Japan. MG and LMG were extracted from spiked samples with
      acetonitrile and citric acid/disodium hydrogen phosphate buffer solution, and
      were salted-out with sodium chloride. The acetonitrile layer was dried over
      anhydrous sodium sulfate and purified on C18 and strongly acidic cation exchange
      columns. MG and LMG in the purified solution were determined quantitatively using
      LC-MS/MS by the internal standard method with surrogates, MG and LMG labeled with
      deuterium (MG-d5, LMG-d6). The recovery rates of MG and LMG were 99.2% and 93.6%,
      respectively. The relative standard deviations of repeatability were 2.2% for MG
      and 4.4% for LMG, and the relative standard deviations of within-laboratory
      reproducibility were 3.5% for MG and 5.1% for LMG. 

PMID- 25748984
TI  - Study of fluorescence probe transfer mechanism based on a new type of excited
      state intramolecular proton transfer.
AB  - 3-Hydroxyflavone (3-HF) is a typical representative of a new type of fluorescent
      molecular probe. The intramolecular proton transfer mechanisms of 3-HF and its
      derivatives have been studied theoretically based on detailed density functional
      theory. An optical physical cycle diagram of intramolecular proton transfer of 3
      HF and its derivatives has been found based on the optimal configuration before
      and after proton transfer. An analysis of the absorption and fluorescence spectra
      of these probes explains their optical physical mechanism, which agrees well with
      experimental results. This correlation indicates that the adopted theory is
      reasonable and effective. The primary bond lengths, angles and infrared
      vibrational spectra indicate that the intramolecular hydrogen bonds were
      strengthened, which is an indication of the excited-state intramolecular proton
      transfer (ESIPT) processes. The constructed potential energy curves of the ground
      and first excited state based on these three chromophores provide the ESIPT
      mechanism, which demonstrates that potential barriers lower than the 6kcal/mol
      and justifies the ESIPT processes occur in the first excited state. The
      fluorescence quenching phenomenon has been explained based on the ESIPT
      mechanism. 

PMID- 25748985
TI  - A novel polymer inclusion membranes based optode for sensitive determination of
      Al3+ ions.
AB  - A novel approach for the determination of Al(3+) from aqueous samples was
      developed using an optode membrane produced by physical inclusion of Al(3+)
      selective reagent, which is morin into a plasticized poly(vinyl chloride). The
      inclusion of Triton X-100 was found to be valuable and useful for enhancing the
      sorption of Al(3+) ions from liquid phase into the membrane phase, thus
      increasing the intensity of optode's absorption. The optode showed a linear
      increase in the absorbance at lambda(max)=425 nm over the concentration range of
      1.85*10(-6)-1.1*10(-4) mol L(-1) (0.05-3 MUg mL(-1)) of Al(3+) ions in aqueous
      solution after 5 min. The limit of detection was determined to be 1.04*10(-6) mol
      L(-1) (0.028 MUg mL(-1)). The optode developed in the present work was easily
      prepared and found to be stable, has good mechanical strength, sensitive and
      reusable. In addition, the optode was tested for Al(3+) determination in lake
      water, river water and pharmaceutical samples, which the result was satisfactory.

PMID- 25748986
TI  - In vitro bioactivity evaluation, mechanical properties and microstructural
      characterization of Na2O-CaO-B2O3-P2O5 glasses.
AB  - Na2O-CaO-B2O3-P2O5 glasses have been prepared by the melt-quenching method. B2O3
      content was systematically increased from 5 to 30 mol%, at the expense of P2O5,
      in the chemical composition of these glasses. Density, Vickers microhardness and
      fracture toughness of the prepared glasses were measured. In vitro bioactivity of
      the glasses was assessed by soaking in the simulated body fluid (SBF) at 37+/-0.5
      degrees C for 3, 7, 14 and 30 days. The glasses were tested in the form of glass
      grains as well as bulk slabs. The structure and composition of the solid reaction
      products were analyzed using X-ray diffraction (XRD), Fourier transform infrared
      spectroscopy (FTIR), transmission electron microscopy (TEM) and scanning electron
      microscopy (SEM) coupled with energy dispersive spectroscopy (EDS). The kinetics
      of degradation of the glass particles were monitored by measuring the weight loss
      of the particles and the ionic concentration of Ca, P and B in the SBF solution
      using inductive coupled plasma-atomic emission spectroscopy (ICP-AES). The
      obtained results revealed the formation of a bioactive hydroxyapatite (HA) layer,
      composed of nano-crystallites, on the surface of glass grains after the in vitro
      assays. The results have been used to understand the formation of HA as a
      function of glass composition and soaking time in the SBF. It can be pointed out
      that increasing B2O3 content in glass composition enhances the bioactivity of
      glasses. The nanometric particle size of the formed HA and in vitro bioactivity
      of the studied glasses make them possible candidates for tissue engineering
      application.

PMID- 25748987
TI  - Synthesis, characterization, fluorescence and catalytic activity of some new
      complexes of unsymmetrical Schiff base of 2-pyridinecarboxaldehyde with 2,6
      diaminopyridine.
AB  - The Schiff base, 2-[(pyridin-2-ylmethylidene)amino]-6-aminopyridine (L) was
      synthesized by 1:1 condensation of 2-pyridinecarboxaldehyde and 2,6
      diaminopyridine. The ligand and its complexes were characterized by different
      physicochemical studies. The analytical and spectroscopic tools indicated that
      the synthesized complexes have the general formulae: [M(L)Cl2].2H2O (M=Cu(II),
      Ni(II) and Co(II)), [La(L)3](NO3)3.3H2O and [Sm(L)(ClO4)3].3H2O. Vibrational
      spectra indicated the coordination of L to metal ions through its pyridyl and
      azomethine nitrogen atoms. The presence of water molecules in all reported
      complexes has been supported by TG/DTA studies. Kinetic and thermodynamic
      parameters were computed using Coats and Redfern method. The prepared ligand and
      its complexes exhibited intraligand (pi-pi*) fluorescence and can potentially
      serve as photoactive materials. The catalytic activity of the complexes toward
      the decomposition of hydrogen peroxide was investigated. Both the ligand and its
      complexes have been screened for antibacterial activities.

PMID- 25748988
TI  - Surface-enhanced Raman spectroscopy of genomic DNA from in vitro grown tomato
      (Lycopersicon esculentum Mill.) cultivars before and after plant
      cryopreservation.
AB  - In this work the surface-enhanced Raman scattering (SERS) spectra of five genomic
      DNAs from non-cryopreserved control tomato plants (Lycopersicon esculentum Mill.
      cultivars Siriana, Darsirius, Kristin, Pontica and Capriciu) respectively, have
      been analyzed in the wavenumber range 400-1800 cm(-1). Structural changes induced
      in genomic DNAs upon cryopreservation were discussed in detail for four of the
      above mentioned tomato cultivars. The surface-enhanced Raman vibrational modes
      for each of these cases, spectroscopic band assignments and structural
      interpretations of genomic DNAs are reported. We have found, that DNA isolated
      from Siriana cultivar leaf tissues suffers the weakest structural changes upon
      cryogenic storage of tomato shoot apices. On the contrary, genomic DNA extracted
      from Pontica cultivar is the most responsive system to cryopreservation process.
      Particularly, both C2'-endo-anti and C3'-endo-anti conformations have been
      detected. As a general observation, the wavenumber range 1511-1652 cm(-1), being
      due to dA, dG and dT residues seems to be influenced by cryopreservation process.
      These changes could reflect unstacking of DNA bases. However, not significant
      structural changes of genomic DNAs from Siriana, Darsirius and Kristin have been
      found upon cryopreservation process of tomato cultivars. Based on this work,
      specific plant DNA-ligand interactions or accurate local structure of DNA in the
      proximity of a metallic surface, might be further investigated using surface
      enhanced Raman spectroscopy.

PMID- 25748989
TI  - Synthesis, X-ray, NMR, FT-IR, UV/vis, DFT and TD-DFT studies of N-(4
      chlorobutanoyl)-N'-(2-, 3- and 4-methylphenyl)thiourea derivatives.
AB  - A new isomers of thiourea derivatives, namely N-(4-chlorobutanoyl)-N'-(2
      methylphenyl)-thiourea (1a), N-(4-chlorobutanoyl)-N'-(3-methylphenyl)thiourea
      (1b) and N-(4-chlorobutanoyl)-N'-(4-methylphenyl)thiourea (1c) have been
      synthesized by refluxing mixture of equimolar amounts of 4
      chlorobutanoylisothiocyanate with 2, 3 or 4-toluidine, respectively. The three
      isomers were characterized by spectroscopic (UV/vis, FT-IR and NMR) and X-ray
      crystallography techniques. To investigate the isomerization effect on
      spectroscopic data, DFT and TD-DFT calculations have been carried out using five
      hybrid functionals (B3LYP, B3P86, CAM-B3LYP, M06-2X and PBE0) to predict UV/vis
      absorption bands (n->pi* and pi->pi*), (1)H and (13)C NMR chemical shifts, FT-IR
      vibration modes and X-ray parameters (bonds, bond angles and torsion angles) for
      1a, 1b and 1c isomers. The results showed that the isomerization effect is
      significant on lambda(MAX) absorption bands, while for IR and NMR the effect is
      negligible. In accordance with previous studies, B3LYP, B3P86 and PBE0 gave the
      most reliable to predict the excitation energies of thiourea derivatives.

PMID- 25748990
TI  - Sonochemical synthesis of LiNi0.5Mn1.5O4 and its electrochemical performance as a
      cathode material for 5 V Li-ion batteries.
AB  - LiNi0.5Mn1.5O4 was synthesized as a cathode material for Li-ion batteries by a
      sonochemical reaction followed by annealing, and was characterized by XRD, SEM,
      HRTEM and Raman spectroscopy in conjunction with electrochemical measurements.
      Two samples were prepared by a sonochemical process, one without using glucose
      (sample-S1) and another with glucose (sample-S2). An initial discharge specific
      capacity of 130 mA h g(-1) is obtained for LiNi0.5Mn1.5O4 at a relatively slow
      rate of C/10 in galvanostatic charge-discharge cycling. The capacity retention
      upon 50 cycles at this rate was around 95.4% and 98.9% for sample-S1 and sample
      S2, respectively, at 30 degrees C.

PMID- 25748991
TI  - Structural properties and interaction energies affecting drug design. An approach
      combining molecular simulations, statistics, interaction energies and neural
      networks.
AB  - In order to elucidate some basic principles for protein-ligand interactions, a
      subset of 87 structures of human proteins with their ligands was obtained from
      the PDB databank. After a short molecular dynamics simulation (to ensure
      structure stability), a variety of interaction energies and structural parameters
      were extracted. Linear regression was performed to determine which of these
      parameters have a potentially significant contribution to the protein-ligand
      interaction. The parameters exhibiting relatively high correlation coefficients
      were selected. Important factors seem to be the number of ligand atoms, the ratio
      of N, O and S atoms to total ligand atoms, the hydrophobic/polar aminoacid ratio
      and the ratio of cavity size to the sum of ligand plus water atoms in the cavity.
      An important factor also seems to be the immobile water molecules in the cavity.
      Nine of these parameters were used as known inputs to train a neural network in
      the prediction of seven other. Eight structures were left out of the training to
      test the quality of the predictions. After optimization of the neural network,
      the predictions were fairly accurate given the relatively small number of
      structures, especially in the prediction of the number of nitrogen and sulfur
      atoms of the ligand. 

PMID- 25748992
TI  - [Interstitial lung disease induced by hydroxychloroquine].

PMID- 25748993
TI  - [A prospective study of drug-facilitated sexual assault in Barcelona].
AB  - BACKGROUND AND OBJECTIVE: To determine the frequency and characteristics of
      suspected drug-facilitated sexual assault (DFSA) among the victims of sexual
      assault in Barcelona. MATERIAL AND METHODS: Prospective study of every adult
      consulting an emergency service because of alleged sexual assault and receiving
      forensic assessment in the city of Barcelona in 2011. RESULTS: A total of 35 of
      114 cases (30.7%) met suspected DFSA criteria. Compared with the other victims,
      suspected DFSA cases were more likely to experience amnesia, to have been
      assaulted by night, after a social situation and by a recently acquainted man, to
      have used alcohol before the assault and to be foreigners. In this group ethanol
      was detected in blood or urine in 48.4% of analyzed cases; their mean back
      calculated blood alcohol concentration was 2.29g/l (SD 0.685). Also, at least one
      central nervous system drug other than ethanol was detected in 60,6%, mainly
      stimulant drugs of abuse. CONCLUSIONS: Suspected DFSA is frequent among victims
      of alleged sexual assault in Barcelona nowadays. The depressor substance most
      commonly encountered is alcohol, which contributes to victims' vulnerability.

PMID- 25748994
TI  - [Actinomyces odontolyticus pneumonia in a patient with iatrogenic A
      hypogammaglobulinemia].

PMID- 25748995
TI  - [Transparency and benchmarking for sustainability of the health system].

PMID- 25748996
TI  - Effects of properties of manganese oxide-impregnated catalysts and flue gas
      condition on multipollutant control of Hg0 and NO.
AB  - This research investigated the effects of manganese oxide (MnOx) impregnation on
      the physical/chemical properties and multi pollutant control effectiveness of
      Hg(0) and NO using a V2O5-WO3/TiO2-SiO2 selective catalytic reduction (SCR)
      catalyst. Raw and MnOx-treated SCR samples were bean-shaped nanoparticles with
      sizes within 10-30 nm. Impregnating MnOx of <= 5 wt% caused limited changes in
      physical properties of the catalyst. The decrease in surface area when the
      impregnated MnOx amount was 10 wt% may stem from the pore blockage and particle
      growth or aggregation of the catalyst. Mn(4+) was the main valence state of
      impregnated MnOx. Apparent crystallinity of MnOx was not observed based on X-ray
      diffraction. MnOx impregnation enhanced the Hg(0) oxidation and NO/SO2 removal of
      SCR catalyst. The 5 and 10% MnOx-impregnated samples had the greatest multi
      pollutant control potentials for Hg(0) oxidation and NO removal; however, the
      increasing SO2 removal that may be mainly due to SO2-SO3 conversion should be
      cautioned. HCl and O2 greatly promoted Hg(0) oxidation. SO2 enhanced Hg(0)
      oxidation at <= 200 ppm while NO and NH3 consistently inhibited Hg(0) oxidation.
      Elevating flue gas temperature enhanced Hg(0) oxidation. Overall, MnOx
      impregnated catalysts show stable and consistent multi pollutant removal
      effectiveness under the test conditions.

PMID- 25748997
TI  - Photoelectrocatalytic activity of a hydrothermally grown branched Zno nanorod
      array electrode for paracetamol degradation.
AB  - Hierarchical branched ZnO nanorod (B-ZnR) arrays as an electrode for efficient
      photoelectrocatalytic degradation of paracetamol were grown on fluorine-doped tin
      oxide substrates using a solution route. The morphologic and structural studies
      show the ZnO trunks are single-crystalline hexagonal wurtzite ZnO with a [0001]
      growth direction and are densely covered by c-axis-oriented ZnO branches. The
      obvious enhancement in photocurrent response of the B-ZnR electrode was obtained
      than that in the ZnO nanoparticle (ZnO NP) electrode. For the
      photoelectrocatalytic degradation of paracetamol in 20 h, the conversion fraction
      of the drug increased from 32% over ZnO NP electrode to 62% over B-ZnR arrays
      with about 3-fold increase in initial reaction rate. The light intensity
      dependent photoelectrocatalytic experiment indicated that the superior
      performance over the B-ZnR electrode was mainly ascribed to the increased
      specific surface area without significantly sacrificing the charge transport and
      pollutant diffusion efficiencies. Two aromatic intermediate compounds were
      observed and eventually converted into harmless carboxylic acids and ammonia.
      Hierarchical tree-like ZnO arrays can be considered effective alternatives to
      improve photoelectro degradation rates without the need for expensive additives.

PMID- 25748998
TI  - Geochemical anomalies of toxic elements and arsenic speciation in airborne
      particles from Cu mining and smelting activities: influence on air quality.
AB  - A characterization of chemical composition and source contribution of PM10 in
      three representative environments of southwest Spain related to mining activities
      (mineral extraction, mining waste and Cu-smelting) has been performed. A study of
      geochemical anomalies was conducted in the samples collected at the three
      stations between July 2012 and October 2013. The influence of Cu-smelting
      processes was compared to other mining activities, where common tracers were
      identified. The Cu and As concentrations in the study area are higher than in
      other rural and urban stations of Spain, in which geochemical anomalies of As,
      Se, Bi, Cd, and Pb have been reported. The results of source contribution showed
      similar geochemical signatures in the industrial and mining factors. However, the
      contribution to PM10 is different according to the type of industrial activity.
      These results have been confirmed performing an arsenic speciation analysis of
      the PM10 samples, in which the mean extraction efficiency of arsenic depended on
      the origin of the samples. These finding indicate that the atmospheric
      particulate matter emitted from Cu-smelting has a high residence time in the
      atmosphere. This indicates that the Cu-smelter can impact areas of high
      ecological interest and considered as clean air. 

PMID- 25748999
TI  - One-pot approach for synthesis of N-doped TiO2/ZnFe2O4 hybrid as an efficient
      photocatalyst for degradation of aqueous organic pollutants.
AB  - N-doped TiO2/ZnFe2O4 catalysts were successfully prepared by coupling nitrogen
      modified TiO2 with ZnFe2O4 via a one-pot vapor-thermal method. The
      physicochemical properties of the as-prepared catalysts have been characterized
      using various spectroscopic and microscopic techniques. The UV-vis-light-driven
      photocatalytic activities of the hybrids were evaluated and the effects of the
      amount of photocatalyst, different types of dyes, catalyst stability on
      photodegradation of organic dyes were investigated. Moreover, degradation
      kinetics and mechanism as well as the roles of N doping, ZnFe2O4 and TiO2 have
      been analyzed. It was revealed that N-doped TiO2/ZnFe2O4 exhibited an improved
      performance compared with TiO2/ZnFe2O4 or ZnFe2O4 because of the formation of a
      heterostructure at the interface as well as the introduction of N species. Active
      species such as holes, electrons, hydroxyl radicals, and superoxide radicals
      involved in the photodegradation process were detected by using different types
      of scavengers. Because of ZnFe2O4 in the hybrid, the catalyst shows
      ferromagnetism, and thus, the hybrid catalyst is easily isolated from the
      reaction mixture after the photocatalytic experiments. This work not only offers
      a simple method for the fabrication of N doped TiO2/ZnFe2O4 hybrids, but also
      provides an effective and conveniently recyclable photocatalyst for the
      purification of water. 

PMID- 25749000
TI  - Parameters influencing ciprofloxacin, ofloxacin, amoxicillin and sulfamethoxazole
      retention by natural and converted calcium phosphates.
AB  - The retention of four antibiotics, ciprofloxacin, ofloxacin, amoxicillin and
      sulfamethoxazole by a natural phosphate rock (francolite) was studied and
      compared with a converted hydroxyapatite powder. The maximum sorption capacities
      were found to correlate with the molecular weight of the molecules. The
      mechanisms of sorption depended mostly on the charge of the antibiotic whereas
      the kinetics of the process was sensitive to their hydrophobic/hydrophilic
      character. The two materials showed slightly distinct affinities for the various
      antibiotics but exhibited similar maximum sorption capacities despite different
      specific surface areas. This was mainly attributed to the more pronounced
      hydrophobic character of the francolite phase constituting the natural phosphate.
      These data enlighten that the retention properties of these mineral phases depend
      on a complex interplay between the inter-molecular and molecule-solid
      interactions. These findings are relevant to understand better the contribution
      of calcium phosphates in the fate and retention of antibiotics in soils. 

PMID- 25749001
TI  - Lymphatic drainage patterns in oral squamous cell carcinoma: findings of the
      ACOSOG Z0360 (Alliance) study.
AB  - OBJECTIVE: The purpose of our study was to correlate sentinel lymph nodes (SLN)
      found on planar lymphoscintigraphy (LS) to SLN found with gamma probe-directed
      sentinel lymph node biopsy (SLNB) for T1/T2 N0 oral cavity cancer. STUDY DESIGN:
      Prospective cooperative group trial. SETTING: Academic medical centers. SUBJECTS
      AND METHODS: One hundred forty adults with untreated T1/T2 N0 squamous cell
      carcinoma (SCC) of the oral cavity underwent planar LS, resection, SLNB, and neck
      dissection. Location of SLN by planar LS and SLNB and of metastases were compared
      to each other and historical data of regional metastases. RESULTS: SLNs located
      by planar LS and SLNB were predominantly in levels I through IV. There was
      heterogeneity in the number of SLNs found at planar LS and at SLNB, which was
      significantly different in levels II and III (P < .0001). In 14 of 33 cases with
      bilateral drainage on planar LS, SLNB detected only unilateral SLN. Sensitivity
      of planar LS in predicting the level of SLN was 41% to 63%, and specificity was
      68% to 95%. Comparison of locations of the metastases to historical data showed
      fewer metastases to level I in our study (P = .03). Metastases occurred
      predominantly in levels I through III. In 1 case of a lateral tongue cancer, a
      contralateral SLN was the only positive node. CONCLUSION: Lymphatic drainage
      patterns and metastases involved predominantly levels I through III. Planar LS is
      not sensitive for predicting the levels of SLN, and in levels II and III, the
      rate of detection of SLN between the 2 modalities is significantly different.

PMID- 25749002
TI  - Predictors of clinical and microbiological treatment failure in neonatal
      bloodstream infections.
AB  - This study aimed to identify independent predictors of clinical and
      microbiological treatment failure and develop a predictive model for neonates
      with bloodstream infection (BSI). This study included 1087 episodes of BSIs in
      793 neonates in a tertiary-level neonatal intensive care unit of northern Taiwan
      between 2004 and 2012. Patient demographics, underlying chronic comorbidities,
      clinical features, antimicrobial treatment and microbiological characteristics
      were evaluated. The presence of underlying congenital anomalies (odds ratio [OR]
      2.12, 95% confidence interval [CI] 1.09 to 4.10) and pulmonary hypertension (OR
      3.63, 95% CI 1.70 to 7.74), infections caused by multidrug-resistant gram
      negative bacteria (OR 2.89, 95% CI 1.23 to 6.79), group B Streptococcus (OR 3.15,
      95% CI 1.33 to 7.46), and fungi (OR 4.13, 95% CI 2.02 to 8.46), a Neonatal
      Therapeutic Intervention Scoring System score of >= 23 (OR 6.96, 95% CI 2.55 to
      28.58), inappropriate antibiotics (OR 2.13, 95% CI 1.41 to 3.23), and concomitant
      meningitis (OR 4.25, 95% CI 2.08 to 8.69) and ventilator-associated pneumonia (OR
      2.73, 95% CI 1.22 to 6.13) were identified as independent risk factors for 28-day
      treatment failure in neonatal BSI. A risk score model was created by adding the
      points for each independent risk factor, and had a c-statistic of 0.83. Patients
      with risk scores of 0, 4, 8, 12 and 15 had estimated 28-day treatment failure
      rates of approximately 3.5%, 17.0%, 53.5%, 86.6% and 95.9%, respectively. This
      predictive model, calculated after documentation of a BSI, reflects a spectrum of
      BSI severity and was associated with subsequent treatment failure through illness
      severity score and case mix variables. This simple score could prove useful in
      clinical and research settings, and practical in estimating the prognosis. 

PMID- 25749004
TI  - Peripapillary choroidal thickness in childhood.
AB  - Changes in the thickness of the invivo peripapillary choroid have been documented
      in a range of ocular conditions in adults; however, choroidal thickness in the
      peripapillary region of children has not been examined in detail. This study
      therefore aimed to investigate the thickness of the peripapillary choroid and the
      overlying retinal nerve fibre layer (RNFL) in a population of normal children
      with a range of refractive errors. Ninety-three children (37 myopes and 56 non
      myopes) aged between 11 and 16 years, had measurements of peripapillary choroidal
      and RNFL thickness derived from enhanced depth imaging optical coherence
      tomography images (EDI-OCT, Heidelberg Spectralis). The average thickness was
      determined in a series of five 0.25 mm width concentric annuli (each divided into
      8 equal sized 45 degrees  sectors) centred on the optic nerve head boundary,
      accounting for individual ocular magnification factors and the disc-fovea angle.
      Significant variations in peripapillary choroidal thickness were found to occur
      with both annulus location (p < 0.001) and sector position (p < 0.001) in this
      population of children. The innermost annulus (closest to the edge of the optic
      disc) exhibited the thinnest choroid (mean 77 +/- 16 MUm) and the outermost
      annulus, the thickest choroid (191 +/- 52 MUm). The choroid was thinnest inferior
      to the optic nerve head (139 +/- 38 MUm) and was thickest in the superior
      temporal sector (157 +/- 40 MUm). Significant differences in the distribution of
      choroidal thickness were also associated with myopia, with myopic children having
      significantly thinner choroids in the inner and outer annuli of the nasal and
      temporal sectors respectively (p < 0.001). RNFL thickness also varied
      significantly with annulus location and sector (p < 0.001), and showed
      differences in thickness distribution associated with refractive error. This
      study establishes the normal variations in the thickness of the peripapillary
      choroid with radial distance and azimuthal angle from the optic nerve head
      boundary. A significant thinning of the peripapillary choroid associated with
      myopia in childhood was also observed in both nasal and temporal regions. The
      changes in peripapillary RNFL and choroidal thickness associated with refractive
      error are consistent with a redistribution of these tissues occurring with myopic
      axial elongation in childhood.

PMID- 25749003
TI  - Susceptibility in vitro of canine methicillin-resistant and -susceptible
      staphylococcal isolates to fusidic acid, chlorhexidine and miconazole:
      opportunities for topical therapy of canine superficial pyoderma.
AB  - OBJECTIVES: Increasing multidrug resistance amongst canine pathogenic
      staphylococci has renewed interest in topical antibacterial therapy for skin
      infections in the context of responsible veterinary prescribing. We therefore
      determined the activity in vitro of three clinically relevant topical agents and
      synergism between two of them against Staphylococcus pseudintermedius and
      Staphylococcus aureus. METHODS: The MICs of fusidic acid (n = 199), chlorhexidine
      (n = 198), miconazole (n = 198) and a 1:1 combination of miconazole/chlorhexidine
      (n = 198) were determined for canine isolates [50 MRSA and 49 methicillin
      resistant S. pseudintermedius (MRSP), 50 MSSA and 50 methicillin-susceptible S.
      pseudintermedius (MSSP)] collected from the UK and Germany using an agar dilution
      method (CLSI VET01-A4). Fractional inhibitory concentration (FIC) indices were
      calculated to assess the interaction of miconazole with chlorhexidine. RESULTS:
      MICs of each drug/combination were significantly (P < 0.0005) higher for S.
      aureus when compared with S. pseudintermedius. Most strains (n = 172) had an MIC
      of fusidic acid of <=0.03 mg/L (MIC >=64 mg/L, n = 5 MRSA). All strains had MICs
      of chlorhexidine of 0.5-4 mg/L, except for one MRSA (MIC = 8 mg/L). All but four
      strains had MICs of miconazole of 1-4 mg/L (MIC = 16 mg/L, n = 3; MIC = 256 mg/L,
      n = 1). Miconazole/chlorhexidine (1:1 ratio) had a synergistic effect against
      49/50 MRSA, 31/50 MSSA, 12/49 MRSP and 23/49 MSSP. CONCLUSIONS: Since the
      majority of these staphylococci, including methicillin-resistant isolates, had
      MICs that should be readily exceeded by topical skin application of these agents,
      their therapeutic efficacy for canine superficial pyoderma should be assessed.
      The synergistic interaction shown in vitro supports further clinical evaluation
      of miconazole/chlorhexidine combination therapy for staphylococcal infection.

PMID- 25749005
TI  - The Aorta-Gonad-Mesonephros Organ Culture Recapitulates 5hmC Reorganization and
      Replication-Dependent and Independent Loss of DNA Methylation in the Germline.
AB  - Removal of cytosine methylation from the genome is critical for reprogramming and
      transdifferentiation and plays a central role in our understanding of the
      fundamental principles of embryo lineage development. One of the major models for
      studying cytosine demethylation is the mammalian germ line during the primordial
      germ cell (PGC) stage of embryo development. It is now understood that oxidation
      of 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC) is required to remove
      cytosine methylation in a locus-specific manner in PGCs; however, the mechanisms
      downstream of 5hmC are controversial and hypothesized to involve either active
      demethylation or replication-coupled loss. In the current study, we used the
      aorta-gonad-mesonephros (AGM) organ culture model to show that this model
      recapitulates germ line reprogramming, including 5hmC reorganization and loss of
      cytosine methylation from Snrpn and H19 imprinting control centers (ICCs). To
      directly address the hypothesis that cell proliferation is required for cytosine
      demethylation, we blocked PI3-kinase-dependent PGC proliferation and show that
      this leads to a G1 and G2/M cell cycle arrest in PGCs, together with retained
      levels of cytosine methylation at the Snrpn ICC, but not at the H19 ICC. Taken
      together, the AGM organ culture model is an important tool to evaluate mechanisms
      of locus-specific demethylation and the role of PI3-kinase-dependent PGC
      proliferation in the locus-specific removal of cytosine methylation from the
      genome. 

PMID- 25749006
TI  - A single bout of dynamic exercise by healthy adults enhances the generation of
      monocyte-derived-dendritic cells.
AB  - The ex vivo generation of monocyte-derived-dendritic cells (mo-DCs) has
      facilitated the use of DCs in immunotherapy research. However, low blood monocyte
      numbers frequently limit the manufacture of sufficient numbers of mo-DCs for
      subsequent experimental and clinical procedures. Because exercise mobilizes
      monocytes to the blood, we tested if acute dynamic exercise by healthy adults
      would augment the generation of mo-DCs without compromising their differentiation
      or function. We compared mo-DC generation from before- and after-exercise blood
      over 8-days of culture. Function was assessed by FITC-dextran uptake and the
      stimulation of autologous cytomegalovirus (pp65)-specific-T-cells. Supporting the
      hypothesis, we found a near fourfold increase in number of mo-DCs generated after
      exercise. Furthermore, relative FITC-dextran uptake, differentiation rate, and
      stimulation of pp65-specific-T-cells did not differ between before- and after
      exercise mo-DCs. We conclude that exercise enhances the ex vivo generation of mo
      DCs without compromising their function, and so may overcome some limitations
      associated with manufacturing these cells for immunotherapy. 

PMID- 25749007
TI  - The aryl hydrocarbon receptor regulates an essential transcriptional element in
      the immunoglobulin heavy chain gene.
AB  - Ig heavy chain (Igh) transcription involves several regulatory elements including
      the 3'Igh regulatory region (3'IghRR). 3'IghRR activity is modulated by several
      transcription factors, including NF-kappaB and AP-1 and potentially the aryl
      hydrocarbon receptor (AhR). The prototypical AhR ligand 2,3,7,8
      tetrachlorodibenzo-p-dioxin (TCDD) inhibits antibody secretion and 3'IghRR
      activity. However, the exact mechanism is unknown and TCDD can modulate NF-kappaB
      and AP-1 in an AhR-independent manner. To determine if the AhR is a significant
      regulator of the 3'IghRR, we utilized a mouse B-cell line that stably expresses a
      3'IghRR-regulated transgene and either an AhR antagonist or shRNA targeting the
      AhR. Disruption of the AhR pathway reversed TCDD-induced suppression of the
      3'IghRR-regulated transgene and of endogenous Ig demonstrating a biologically
      significant effect of the AhR on 3'IghRR activation. Altered human 3'IGHRR
      activity by AhR ligands, which include dietary, environmental, and pharmaceutical
      chemicals, may have significant implications to human diseases previously
      associated with the 3'IGHRR. 

PMID- 25749008
TI  - ERK1/2 acts as a switch between necrotic and apoptotic cell death in ether
      phospholipid edelfosine-treated glioblastoma cells.
AB  - Glioblastoma is characterized by constitutive apoptosis resistance and survival
      signaling expression, but paradoxically is a necrosis-prone neoplasm. Incubation
      of human U118 glioblastoma cells with the antitumor alkylphospholipid analog
      edelfosine induced a potent necrotic cell death, whereas apoptosis was scarce.
      Preincubation of U118 cells with the selective MEK1/2 inhibitor U0126, which
      inhibits MEK1/2-mediated activation of ERK1/2, led to a switch from necrosis to
      caspase-dependent apoptosis following edelfosine treatment. Combined treatment of
      U0126 and edelfosine totally inhibited ERK1/2 phosphorylation, and led to RIPK1
      and RelA/NF-kappaB degradation, together with a strong activation of caspase-3
      and -8. This apoptotic response was accompanied by the activation of the
      intrinsic apoptotic pathway with mitochondrial transmembrane potential loss, Bcl
      xL degradation and caspase-9 activation. Inhibition of ERK phosphorylation also
      led to a dramatic increase in edelfosine-induced apoptosis when the
      alkylphospholipid analog was used at a low micromolar range, suggesting that ERK
      phosphorylation acts as a potent regulator of apoptotic cell death in edelfosine
      treated U118 cells. These data show that inhibition of MEK1/2-ERK1/2 signaling
      pathway highly potentiates edelfosine-induced apoptosis in glioblastoma U118
      cells and switches the type of edelfosine-induced cell death from necrosis to
      apoptosis. 

PMID- 25749009
TI  - The incidence and burden of hospital-treated sports-related injury in people aged
      15+ years in Victoria, Australia, 2004-2010: a future epidemic of osteoarthritis?
AB  - OBJECTIVES: Previous sports injury is a known risk factor for subsequent
      osteoarthritis (OA), but population-based rates of sports injury are unknown. The
      aims of this study were to: (1) describe the trends in the population incidence
      and burden of all hospital-treated sports injury in Victoria, Australia in adults
      aged 15+ years; (2) determine the incidence of lower limb and knee injuries; and
      (3) quantify their population health burden as average direct hospital costs per
      injury and lengths of stay. METHODS: Health sector data relating to adults aged
      15+ years, for 2004-2010 inclusive, was extracted from the Victorian Admitted
      Episodes Dataset (VAED) and Victorian Emergency Minimum Dataset (VEMD). Data
      relating to sports injuries were identified using activity codes in each dataset
      Trends in injury frequency and rates were determined, and economic burden was
      calculated. RESULTS: The overall annual rate of hospital treated sports injuries
      increased by 24% (P = 0.001), and lower limb injuries by 26% (P = 0.001) over the
      7 years. The associated accumulated economic burden was $265 million for all
      sports injuries and $110 million for lower limb injuries over the 7-years.
      CONCLUSIONS: The findings of this study show a significant increase in sports
      injuries in the state of Victoria, Australia over a 7-year period. As previous
      sports injury is a risk factor for the development of OA, the future incidence of
      OA will escalate, placing an even greater burden on health care systems.
      Population-wide preventative strategies that reduce the risk of sports injury are
      urgently required in order to reduce the future burden of OA.

PMID- 25749010
TI  - Ankle motion influences the external knee adduction moment and may predict who
      will respond to lateral wedge insoles?: an ancillary analysis from the SILK
      trial.
AB  - OBJECTIVE: Lateral wedge insoles are a potential simple treatment for medial knee
      osteoarthritis (OA) patients by reducing the external knee adduction moment
      (EKAM). However in some patients, an increase in their EKAM is seen.
      Understanding the role of the ankle joint complex in the response to lateral
      wedge insoles is critical in understanding and potentially identifying why some
      patients respond differently to lateral wedge insoles. METHOD: Participants with
      medial tibiofemoral OA underwent gait analysis whilst walking in a control shoe
      and a lateral wedge insole. We evaluated if dynamic ankle joint complex coronal
      plane biomechanical measures could explain and identify those participants that
      increased (biomechanical non-responder) or decreased (biomechanical responder)
      EKAM under lateral wedge conditions compared to the control shoe. RESULTS: Of the
      70 participants studied (43 male), 33% increased their EKAM and 67% decreased
      their EKAM. Overall, lateral wedge insoles shifted the centre of foot pressure
      laterally, increased eversion of the ankle/subtalar joint complex (STJ) and the
      eversion moment compared to the control condition. Ankle angle at peak EKAM and
      peak eversion ankle/STJ complex angle in the control condition predicted if
      individuals were likely to decrease EKAM under lateral wedge conditions.
      CONCLUSIONS: Coronal plane ankle/STJ complex biomechanical measures play a key
      role in reducing EKAM when wearing lateral wedge insoles. These findings may
      assist in the identification of those individuals that could benefit more from
      wearing lateral wedge insoles.

PMID- 25749011
TI  - Enrichment of committed human nucleus pulposus cells expressing chondroitin
      sulfate proteoglycans under alginate encapsulation.
AB  - OBJECTIVE: Intervertebral disc (IVD) degeneration is associated with a
      malfunction of the nucleus pulposus (NP). Alginate culturing provides a favorable
      microenvironment for the phenotypic maintenance of chondrocyte-like NP cells.
      However, NP cells are recently evidenced to present heterogeneous populations,
      including progenitors, fibroblastic cells and primitive NP cells. The aim of this
      study is to profile the phenotypic changes of distinct human NP cells populations
      and describe the dynamic expression of chondroitin sulfate glycosaminoglycans (CS
      GAGs) in extended alginate encapsulation. METHOD: Non-degenerated (ND-NPC) and
      degenerated (D-NPC) NP cells were expanded in monolayers, and subject to 28-day
      culture in alginate after serial passaging. CS-GAG compositional expression in
      monolayer-/alginate-cultured NP cells was evaluated by carbohydrate
      electrophoresis. Cellular phenotypic changes were assessed by immunologic
      detection and gene expression analysis. RESULTS: Relative to D-NPC, ND-NPC
      displayed remarkably higher expression levels of chondroitin-4-sulfate GAGs over
      the 28-day culture. Compared with monolayer culture, ND-NPC showed increased NP
      marker expression of KRT18, KRT19, and CDH2, as well as chondrocyte markers SOX9
      and MIA in alginate culture. In contrast, expression of fibroblastic marker
      COL1A1, COL3A1, and FN1 were reduced. Interestingly, ND-NPC showed a loss of
      Tie2+ but gain in KRT19+/CD24+ population during alginate culture. In contrast, D
      NPC showed more consistent expression levels of NP surface markers during
      culture. CONCLUSION: We demonstrate for the first time that extended alginate
      culture selectively enriches the committed NP cells and favors chondroitin-4
      sulfate proteoglycan production. These findings suggest its validity as a model
      to investigate IVD cell function.

PMID- 25749012
TI  - Pain sensitization in people with knee osteoarthritis: a systematic review and
      meta-analysis.
AB  - OBJECTIVE: Emerging evidence suggests that pain sensitization plays an important
      role in pain associated with knee osteoarthritis (OA). This systematic review and
      meta-analysis examined the evidence for pain sensitization in people with knee OA
      and the relationship between pain sensitization and symptom severity. METHODS: A
      search of electronic databases and reference lists was carried out. All full text
      observational studies published between 2000 and 2014 with the aim of
      investigating pain sensitization in humans with knee OA using quantitative
      sensory testing (QST) measures of hyperalgesia and central hyperexcitability were
      eligible for inclusion. Meta-analysis of data was carried out using a random
      effects model, which included results comparing knee OA participants to controls,
      and results comparing high symptom severity to low symptom severity. RESULTS:
      Fifteen studies were identified following screening and quality appraisal. For
      the meta-analysis, pressure pain threshold (PPT) and heat pain threshold (HPT)
      means and standard deviations were pooled using random effects models. The point
      estimate was large for differences in PPTs between knee OA participants and
      controls [-0.85; confidence interval (CI): -1.1 to -0.6], and moderate for PPT
      differences between knee OA participants with high symptom severity vs those with
      low symptom severity (0.51; CI: -0.73 to -0.30). A small point estimate was found
      for differences in HPTs between knee OA participants and controls (-0.42; CI: 
      0.87 to 0.02). CONCLUSION: Evidence from this systematic review and meta-analysis
      suggests that pain sensitization is present in people with knee OA and may be
      associated with knee OA symptom severity.

PMID- 25749013
TI  - Vaginal bleeding and hemorrhagic prepatellar bursitis in a preadolescent girl,
      possibly related to fluoxetine.

PMID- 25749014
TI  - SAR refinement of antileishmanial N(2),N(4)-disubstituted quinazoline-2,4
      diamines.
AB  - Visceral leishmaniasis is a neglected parasitic disease that has a high fatality
      rate in the absence of treatment. New drugs that are inexpensive, orally active,
      and effective could be useful tools in the fight against this disease. We
      previously showed that N(2),N(4)-disubstituted quinazoline-2,4-diamines displayed
      low- to sub-micromolar potency against intracellular Leishmania, and lead
      compound N(4)-(furan-2-ylmethyl)-N(2)-isopropyl-7-methylquinazoline-2,4-diamine
      (4) exhibited modest efficacy in an acute murine model of visceral leishmaniasis.
      In the present work, thirty-one N(2),N(4)-disubstituted quinazoline-2,4-diamines
      that had not previously been examined for their antileishmanial activity were
      evaluated for their potency and selectivity against Leishmania donovani, the
      causative parasite of visceral leishmaniasis. Quinazoline-2,4-diamines with
      aromatic substituents at both N(2) and N(4) exhibited potent in vitro
      antileishmanial activity but relatively low selectivity, while compounds
      substituted with small alkyl groups at either N(2) or N(4) generally showed lower
      antileishmanial potency but were less toxic to a murine macrophage cell line.
      Based on their in vitro antileishmanial potency, N(4)-benzyl-N(2)-(4
      chlorobenzyl)quinazoline-2,4-diamine (15) and N(2)-benzyl-N(4)
      isopropylquinazoline-2,4-diamine (40) were selected for in vivo evaluation of
      their pharmacokinetic and antileishmanial properties. While 15 displayed a longer
      plasma half-life and a greater area under the curve than 40, both compounds
      showed low efficacy in an acute murine visceral leishmaniasis model. Although the
      present study did not identify new quinazoline-2,4-diamines with promising in
      vivo efficacy, the reduced in vitro toxicity of derivatives bearing small alkyl
      groups at either N(2) or N(4) may provide clues for the design of safe and
      effective antileishmanial quinazolines. 

PMID- 25749015
TI  - Plasmid DNA mono-ion complex stabilized by hydrogen bond for in vivo diffusive
      gene delivery.
AB  - Our original concept of the mono-ion complex (MIC) between plasmid DNA (pDNA) and
      a monocationic biocompatible polymer has been stabilized by hydrogen bond
      formation. To form the hydrogen bond with pDNA, omega-amide-pentylimidazolium end
      modified poly(ethylene glycol), that is, APe-Im-PEG, has been synthesized.
      Agarose gel retardation assay and circular dichroism measurement have revealed
      that the MIC between pDNA and APe-Im-PEG has been stabilized by the hydrogen bond
      between pDNA and the omega-amide group and that the stable MIC has surprisingly
      further migrated into gel, as compared with naked pDNA. The rise of melting
      temperature suggests that the specific hydrogen bond forms between an adenine
      thymine base pair and the omega-amide group. The resulting pDNA MIC with APe-Im
      PEG has enhanced gene expression by intramuscular administration in mice, as
      compared with a poly(ethylenimine) polyion complex (PIC). These results suggest
      that the pDNA MIC is diffusive in vivo administration site, as compared with pDNA
      PICs. Our methodology for MIC stabilization by a omega-amide group is expected to
      offer superior supramolecular systems to those by ubiquitous PICs for in vivo
      diffusive gene delivery. 

PMID- 25749016
TI  - Prion protein fragment (106-126) induces prothrombotic state by raising platelet
      intracellular calcium and microparticle release.
AB  - Prion diseases are neurodegenerative disorders where infectious prion proteins
      (PrP) accumulate in brain leading to aggregation of amyloid fibrils and neuronal
      cell death. The amino acid sequence 106-126 from prion proteins, PrP(106-126), is
      highly amyloidogenic and implicated in prion-induced pathologies. As PrP is known
      to be expressed in blood following leakage from brain tissue, we sought to
      investigate its biological effects on human platelets, which have been widely
      employed as 'peripheral' model for neurons. Our findings suggested that, PrP(106
      126) (20MUM) induced dramatic 30-fold rise in intracellular calcium (from 105+/
      30 to 3425+/-525nM) in platelets, which was attributable to influx from
      extracellular fluid with comparatively less contribution from intracellular
      stores. Calcium mobilization was associated with 8-10-fold stimulation in the
      activity of thiol protease calpain that led to partial cleavage of cytoskeleton
      associated protein talin and extensive shedding of microparticles from platelets,
      thus transforming platelets to 'activated' phenotype. Both proteolysis of talin
      and microparticle release were precluded by calpeptin, a specific inhibitor of
      calpain. As microparticles are endowed with phosphatidylserine-enriched surface
      and hence are pro-coagulant in nature, exposure to prion favored a thrombogenic
      state in the organism. 

PMID- 25749017
TI  - Attention/vigilance in schizophrenia: performance results from a large multi-site
      study of the Consortium on the Genetics of Schizophrenia (COGS).
AB  - Attention/vigilance impairments are present in individuals with schizophrenia
      across psychotic and remitted states and in their first-degree relatives. An
      important question is whether deficits in attention/vigilance can be consistently
      and reliably measured across sites varying in many participant demographic,
      clinical, and functional characteristics, as needed for large-scale genetic
      studies of endophenotypes. We examined Continuous Performance Test (CPT) data
      from phase 2 of the Consortium on the Genetics of Schizophrenia (COGS-2), the
      largest-scale assessment of cognitive and psychophysiological endophenotypes
      relevant to schizophrenia. The CPT data from 2251 participants from five sites
      were examined. A perceptual-load vigilance task (the Degraded Stimulus CPT or DS
      CPT) and a memory-load vigilance task (CPT-Identical Pairs or CPT-IP) were
      utilized. Schizophrenia patients performed more poorly than healthy comparison
      subjects (HCS) across sites, despite significant site differences in participant
      age, sex, education, and racial distribution. Patient-HCS differences in
      signal/noise discrimination (d') in the DS-CPT varied significantly across sites,
      but averaged a medium effect size. CPT-IP performance showed large patient-HCS
      differences across sites. Poor CPT performance was independent of or weakly
      correlated with symptom severity, but was significantly associated with lower
      educational achievement and functional capacity. Current smoking was associated
      with poorer CPT-IP d'. Patients taking both atypical and typical antipsychotic
      medication performed more poorly than those on no or atypical antipsychotic
      medications, likely reflecting their greater severity of illness. We conclude
      that CPT deficits in schizophrenia can be reliably detected across sites, are
      relatively independent of current symptom severity, and are related to functional
      capacity. 

PMID- 25749018
TI  - Proinflammatory cytokines and their membrane-bound receptors are altered in the
      lymphocytes of schizophrenia patients.
AB  - Abnormalities of protein levels of proinflammatory cytokines and their soluble
      receptors have been reported in the plasma/serum of schizophrenia (SZ) patients.
      To examine if SZ is also associated with the abnormal gene expression of
      cytokines and their membrane-bound receptors, we studied mRNA expression of
      proinflammatory cytokines and their receptors in lymphocytes of SZ patients and
      normal control (NC) subjects. We determined the protein and mRNA expression of
      proinflammatory cytokines and mRNA expression of their receptors in lymphocytes
      from 30 SZ patients and 30 drug-free NC subjects. The subjects were diagnosed
      according to DSM-IV criteria. Protein levels of cytokines were determined by
      ELISA, and mRNA levels in lymphocytes were determined by the qPCR method. We
      found that the mRNA levels of IL-6, TNF-alpha, IL-1R1, TNFR1, and TNFR2, but not
      IL-1beta, IL-1R2, IL-1RA, IL-6R, or GP130 were significantly increased in
      lymphocytes of SZ patients compared with NC subjects. We also found that the
      protein expression of IL-6 and TNF-alpha, but not IL-1beta, was also
      significantly increased in SZ patients compared with NC subjects. These studies
      suggest that in addition to the reported abnormalities of proinflammatory
      cytokines and their soluble receptors in the plasma of SZ patients, an abnormal
      gene expression of these cytokines and their membrane-bound receptors may be
      involved in the pathogenesis of SZ. 

PMID- 25749019
TI  - Social cognitive functioning in prodromal psychosis: A meta-analysis.
AB  - BACKGROUND: There is substantial evidence regarding a social cognitive deficit in
      schizophrenia, and it has been suggested to be a trait-marker of this disorder.
      However, a domain-by-domain analysis of social cognitive deficits in individuals
      at clinical high risk (CHR) for psychosis has not been performed. METHOD:
      Electronic databases were searched for studies regarding social cognitive
      performance in individuals at CHR. The included social cognitive domains, which
      were classified based on the Social Cognition Psychometric Evaluation (SCOPE)
      initiative of the National Institute of Mental Health (NIMH), were as follows:
      theory of mind (ToM), social perception (SP), attributional bias (AB), and
      emotion processing (EP). RESULTS: Twenty studies that included 1229 individuals
      at CHR and 825 healthy controls met the inclusion criteria. The overall effect
      size for social cognition was medium (g=-0.477). The largest effect size was
      identified for AB (g=-0.708). A medium effect size was identified for EP (g=
      0.446) and ToM (g=-0.425), and small effects were identified for SP (g=-0.383).
      CONCLUSION: This is the first quantitative domain-by-domain social cognitive meta
      analysis regarding CHR individuals. The present study indicated that individuals
      at CHR exhibited significant impairments in all domains of social cognition
      compared with healthy controls, with the largest effect size identified for AB.
      The identification of social cognitive domains that reflect an increased risk for
      impending psychosis and of predictors of the conversion to psychosis via a
      longitudinal follow-up study is required.

PMID- 25749020
TI  - Building models for postmortem abnormalities in hippocampus of schizophrenics.
AB  - Postmortem studies have suggested that there is abnormal GABAergic activity in
      the hippocampus in schizophrenia (SZ). In micro-dissected human hippocampal
      slices, a loss of interneurons and a compensatory upregulation of GABAA receptor
      binding activity on interneurons, but not PNs, has suggested that disinhibitory
      GABA-to-GABA connections are abnormal in stratum oriens (SO) of CA3/2, but not
      CA1, in schizophrenia. Abnormal expression changes in the expression of kainate
      receptor (KAR) subunits 5, 6 and 7, as well as an inwardly-rectifying
      hyperpolarization-activated cationic channel (Ih3; HCN3) may play important roles
      in regulating GABA cell activity at the SO CA3/2 locus. The exclusive neurons at
      this site are GABAergic interneurons; these cells also receive direct projections
      from the basolateral amygdala (BLA). When the BLA is stimulated by stereotaxic
      infusion of picrotoxin in rats, KARs influence axodendritic and presynaptic
      inhibitory mechanisms that regulate both inhibitory and disinhibitory
      interneurons in the SO-CA3/2 locus. The rat model described here was specifically
      developed to extend our understanding of these and other postmortem findings and
      has suggested that GABAergic abnormalities and possible disturbances in
      oscillatory rhythms may be related to a dysfunction of disinhibitory interneurons
      at the SO-CA3/2 site of schizophrenics. 

PMID- 25749021
TI  - Development of loop-mediated isothermal amplification (LAMP) for detection of
      Babesia gibsoni infection in dogs.
AB  - Diagnosis of canine babesiosis, caused by Babesia gibsoni is difficult,
      especially in chronically infected dogs. A loop mediated isothermal amplification
      (LAMP) assay was developed and standardized by using four oligonucleotide primers
      targeting the hypervariable region of 18S rRNA gene (GenBank Acc. no. KC461261).
      The primers specifically amplified B. gibsoni DNA, while no amplification was
      detected with DNA from non-infected dogs as well as from dogs infected with
      Babesia canis vogeli, Hepatozoon canis, Ehrlichia canis and Trypanosoma evansi.
      The assay could detect 1.35 * 10(-7) parasitaemia and 10(-4) dilution of
      recombinant plasmid, equivalent to 12 pg of target DNA. All the samples were
      tested by nested PCR as well as LAMP assay. LAMP was found to be 10 times more
      sensitive than nested PCR targeting the same gene. Out of 75 suspected field
      samples, collected from different parts of the country, LAMP could detect B.
      gibsoni in 43 samples, while nested PCR and microscopy could detect 37 and 23
      samples, respectively. High sensitivity, specificity and rapidity of LAMP assay
      may be exploited for screening large number of samples in a field setting.

PMID- 25749022
TI  - Sepsis drives the cost in perforated peptic ulcer.

PMID- 25749023
TI  - Primary systemic therapy for breast cancer: Does the patient's involvement in
      decision-making create a new future?
AB  - OBJECTIVE: Primary systemic therapy (PST) followed by surgery is the standard
      initial treatment for locally advanced breast cancer (LABC). However, some
      patients are averse to mastectomy or breast-conserving surgery and do not consent
      to these procedures. The reasons for this controversial decision, the factors
      influencing the decision-making and optimal solutions for decision aiding need to
      be investigated. METHODS: We addressed these questions by a review of literature
      on the possibilities associated with different patient choices and subsequent
      treatment options in relation to LABC. RESULTS: A total of 5 reviews and 22
      clinical studies were summarized in relation to decision making and the most
      successful decision aids. A discussion is given of the issues of those few
      patients who cannot be convinced to undergo surgery. CONCLUSION: Currently there
      is no guideline for the treatment of patients who reject the surgical procedures
      after PST. Medical oncologists should be able to apply decision aid modalities in
      a personalized manner to give all needed information to their patients thereby
      ensuring a deliberate decision-making process, facilitating acceptance of a need
      for surgery, and thus improving the chances of prolonged survival. PRACTICE
      IMPLICATIONS: Currently multidisciplinary tumor boards are the most suitable
      decision aids in oncological practice.

PMID- 25749024
TI  - Releasing test results directly to patients: A multisite survey of physician
      perspectives.
AB  - OBJECTIVE: To determine physician perspectives about direct notification of
      normal and abnormal test results. METHODS: We conducted a cross-sectional survey
      at five clinical sites in the US and Australia. The US-based study was conducted
      via web-based survey of primary care physicians and specialists between July and
      October 2012. An identical paper-based survey was self-administered between June
      and September 2012 with specialists in Australia. RESULTS: Of 1417 physicians
      invited, 315 (22.2%) completed the survey. Two-thirds (65.3%) believed that
      patients should be directly notified of normal results, but only 21.3% were
      comfortable with direct notification of clinically significant abnormal results.
      Physicians were more likely to endorse direct notification of abnormal results if
      they believed it would reduce the number of patients lost to follow-up (OR=4.98,
      95%CI=2.21-1.21) or if they had personally missed an abnormal test result
      (OR=2.95, 95%CI=1.44-6.02). Conversely, physicians were less likely to endorse if
      they believed that direct notification interfered with the practice of medicine
      (OR=0.39, 95%CI=0.20-0.74). CONCLUSION: Physicians we surveyed generally favor
      direct notification of normal results but appear to have substantial concerns
      about direct notification of abnormal results. PRACTICE IMPLICATIONS: Widespread
      use of direct notification should be accompanied by strategies to help patients
      manage test result abnormalities they receive.

PMID- 25749025
TI  - Fix and forget or fix and report: a qualitative study of tensions at the front
      line of incident reporting.
AB  - INTRODUCTION: Practitioners frequently encounter safety problems that they
      themselves can resolve on the spot. We ask: when faced with such a problem, do
      practitioners fix it in the moment and forget about it, or do they fix it in the
      moment and report it? We consider factors underlying these two approaches.
      METHODS: We used a qualitative case study design employing in-depth interviews
      with 40 healthcare practitioners in a tertiary care hospital in Ontario, Canada.
      We conducted a thematic analysis, and compared the findings with the literature.
      RESULTS: 'Fixing and forgetting' was the main choice that most practitioners made
      in situations where they faced problems that they themselves could resolve. These
      situations included (A) handling near misses, which were seen as unworthy of
      reporting since they did not result in actual harm to the patient, (B)
      prioritising solving individual patients' safety problems, which were viewed as
      unique or one-time events and (C) encountering re-occurring safety problems,
      which were framed as inevitable, routine events. In only a few instances was
      'fixing and reporting' mentioned as a way that the providers dealt with problems
      that they could resolve. CONCLUSIONS: We found that generally healthcare
      providers do not prioritise reporting if a safety problem is fixed. We argue that
      fixing and forgetting patient safety problems encountered may not serve patient
      safety as well as fixing and reporting. The latter approach aligns with recent
      calls for patient safety to be more preventive. We consider implications for
      practice.

PMID- 25749026
TI  - Bad assumptions on primary care diagnostic errors. Response to: 'Advancing the
      science of measurement of diagnostic errors in healthcare: the Safer Dx
      framework' by Singh and Sittig.

PMID- 25749027
TI  - Pay-for-performance policy and data-driven decision making within nursing homes:
      a qualitative study.
AB  - INTRODUCTION: Health systems globally and within the USA have introduced nursing
      home pay-for-performance (P4P) programmes in response to the need for improved
      nursing home quality. Central to the challenge of administering effective P4P is
      the availability of accurate, timely and clinically appropriate data for decision
      making. We aimed to explore ways in which data were collected, thought about and
      used as a result of participation in a P4P programme. METHODS: Semistructured
      interviews were conducted with 232 nursing home employees from within 70 nursing
      homes that participated in P4P-sponsored quality improvement (QI) projects.
      Interview data were analysed to identify themes surrounding collecting, thinking
      about and using data for QI decision making. RESULTS: The term 'data' appeared
      247 times in the interviews, and over 92% of these instances (228/247) were
      spontaneous references by nursing home staff. Overall, 34% of respondents
      (79/232) referred directly to 'data' in their interviews. Nursing home leadership
      more frequently discussed data use than direct care staff. Emergent themes
      included using data to identify a QI problem, gathering data in new ways at the
      local level, and measuring outcomes in response to P4P participation. Alterations
      in data use as a result of policy change were theoretically consistent with the
      revised version of the Promoting Action on Research Implementation in Health
      Services framework, which posits that successful implementation is a function of
      evidence, context and facilitation. CONCLUSIONS: Providing a reimbursement
      context that facilitates the collection and use of reliable local evidence may be
      an important consideration to others contemplating the adaptation of P4P
      policies.

PMID- 25749028
TI  - Application of a trigger tool in near real time to inform quality improvement
      activities: a prospective study in a general medicine ward.
AB  - BACKGROUND: Retrospective record review using trigger tools remains the most
      widely used method for measuring adverse events (AEs) to identify targets for
      improvement and measure temporal trends. However, medical records often contain
      limited information about factors contributing to AEs. We implemented an
      augmented trigger tool that supplemented record review with debriefing front-line
      staff to obtain details not included in the medical record. We hypothesised that
      this would foster the identification of factors contributing to AEs that could
      inform improvement initiatives. METHOD: A trained observer prospectively
      identified events in consecutive patients admitted to a general medical ward in a
      tertiary care academic medical centre (November 2010 to February 2011 inclusive),
      gathering information from record review and debriefing front-line staff in near
      real time. An interprofessional team reviewed events to identify preventable and
      potential AEs and characterised contributing factors using a previously published
      taxonomy. RESULTS: Among 141 patients, 14 (10%; 95% CI 5% to 15%) experienced at
      least one preventable AE; 32 patients (23%; 95% CI 16% to 30%) experienced at
      least one potential AE. The most common contributing factors included policy and
      procedural problems (eg, routine protocol violations, conflicting policies; 37%),
      communication and teamwork problems (34%), and medication process problems (23%).
      However, these broad categories each included distinct subcategories that seemed
      to require different interventions. For instance, the 32 identified communication
      and teamwork problems comprised 7 distinct subcategories (eg, ineffective
      intraprofessional handovers, poor interprofessional communication, lacking a
      shared patient care, paging problems). Thus, even the major categories of
      contributing factors consisted of subcategories that individually related to a
      much smaller subset of AEs. CONCLUSIONS: Prospective application of an augmented
      trigger tool identified a wide range of factors contributing to AEs. However, the
      majority of contributing factors accounted for a small number of AEs, and more
      general categories were too heterogeneous to inform specific interventions.
      Successfully using trigger tools to stimulate quality improvement activities may
      require development of a framework that better classifies events that share
      contributing factors amenable to the same intervention.

PMID- 25749029
TI  - Effect of taurine on rat Achilles tendon healing.
AB  - Taurine has anti-inflammatory and antioxidant characteristics. We have introduced
      taurine into a tendon-healing model to evaluate its effects on tendon healing and
      adhesion formation. Two groups of 16 rats underwent diversion and repair of the
      Achilles tendon. One group received a taurine injection (200 mg/ml) at the repair
      site, while the other group received 1 ml of saline. Specimens were harvested at
      6 weeks and underwent biomechanical and histological evaluation. No tendon
      ruptured. Average maximum load was significantly greater in the taurine-applied
      group compared with the control group (p < 0.05). Similarly, average energy
      uptake was significantly higher in the taurine-applied group compared with the
      control group (p < 0.05). We observed no significant differences in stiffness in
      both groups (p > 0.05). After histological assessment, we found that fibroblast
      proliferation, edema, and inflammation statistically decreased in the treatment
      group (p < 0.05). These findings could indicate greater tendon strength with less
      adhesion formation, and taurine may have an effect on adhesion formation. 

PMID- 25749031
TI  - FAK activation is required for IGF1R-mediated regulation of EMT, migration, and
      invasion in mesenchymal triple negative breast cancer cells.
AB  - Triple negative breast cancer (TNBC) is a highly metastatic disease that
      currently lacks effective prevention and treatment strategies. The insulin-like
      growth factor 1 receptor (IGF1R) and focal adhesion kinase (FAK) signaling
      pathways function in numerous developmental processes, and alterations in both
      are linked with a number of common pathological diseases. Overexpression of IGF1R
      and FAK are closely associated with metastatic breast tumors. The present study
      investigated the interrelationship between IGF1R and FAK signaling in regulating
      the malignant properties of TNBC cells. Using small hairpin RNA (shRNA)-mediated
      IGF1R silencing methods, we showed that IGF1R is essential for sustaining
      mesenchymal morphologies of TNBC cells and modulates the expression of EMT
      related markers. We further showed that IGF1R overexpression promotes migratory
      and invasive behaviors of TNBC cell lines. Most importantly, IGF1R-driven
      migration and invasion is predominantly mediated by FAK activation and can be
      suppressed using pharmacological inhibitors of FAK. Our findings in TNBC cells
      demonstrate a novel role of the IGF1R/FAK signaling pathway in regulating
      critical processes involved in the metastatic cascade. These results may improve
      the current understanding of the basic molecular mechanisms of TNBC metastasis
      and provide a strong rationale for co-targeting of IGF1R and FAK as therapy for
      mesenchymal TNBCs. 

PMID- 25749030
TI  - Subthreshold IKK activation modulates the effector functions of primary mast
      cells and allows specific targeting of transformed mast cells.
AB  - Mast cell differentiation and proliferation depends on IL-3. IL-3 induces the
      activation of MAP-kinases and STATs and consequently induces proliferation and
      survival. Dysregulation of IL-3 signaling pathways also contribute to
      inflammation and tumorigenesis. We show here that IL-3 induces a SFK- and Ca2+
      dependent activation of the inhibitor of kappaB kinases 2 (IKK2) which results in
      mast cell proliferation and survival but does not induce IkappaBalpha-degradation
      and NFkappaB activation. Therefore we propose the term "subthreshold IKK
      activation".This subthreshold IKK activation also primes mast cells for enhanced
      responsiveness to IL-33R signaling. Consequently, co-stimulation with IL-3 and IL
      33 increases IKK activation and massively enhances cytokine production induced by
      IL-33.We further reveal that in neoplastic mast cells expressing constitutively
      active Ras, subthreshold IKK activation is associated with uncontrolled
      proliferation. Consequently, pharmacological IKK inhibition reduces tumor growth
      selectively by inducing apoptosis in vivo.Together, subthreshold IKK activation
      is crucial to mediate the full IL-33-induced effector functions in primary mast
      cells and to mediate uncontrolled proliferation of neoplastic mast cells. Thus,
      IKK2 is a new molecularly defined target structure.

PMID- 25749032
TI  - miR-27a and miR-27a* contribute to metastatic properties of osteosarcoma cells.
AB  - Osteosarcoma (OS) is the most common primary malignant bone tumor in adolescents
      and young adults. The essential mechanisms underlying osteosarcomagenesis and
      progression continue to be obscure. MicroRNAs (miRNAs) have far-reaching effects
      on the cellular biology of development and cancer. We recently reported that
      unique miRNA signatures associate with the pathogenesis and progression of OS. Of
      particular interest, we found that higher expression of miR-27a is associated
      with clinical metastatic disease. We report here that overexpression of miR
      27a/miR-27a*, a microRNA pair derived from a single precursor, promotes pulmonary
      OS metastases formation. By contrast, sequestering miR-27a/miR-27a* by sponge
      technology suppressed OS cells invasion and metastases formation. miR-27a/miR
      27a* directly repressed CBFA2T3 expression among other target genes. We
      demonstrated that CBFA2T3 is downregulated in majority of OS samples and its over
      expression significantly attenuated OS metastatic process mediated by miR-27a/miR
      27a* underscoring CBFA2T3 functions as a tumor suppressor in OS. These findings
      establish that miR-27a/miR-27a* pair plays a significant role in OS metastasis
      and proposes it as a potential diagnostic and therapeutic target in managing OS
      metastases. 

PMID- 25749033
TI  - Global analysis of H3K4me3 and H3K27me3 profiles in glioblastoma stem cells and
      identification of SLC17A7 as a bivalent tumor suppressor gene.
AB  - Epigenetic changes, including H3K4me3 and H3K27me3 histone modification, play an
      important role in carcinogenesis. However, no genome-wide histone modification
      map has been generated for gliomas. Here, we report a genome-wide map of H3K4me3
      and H3K27me3 histone modifications for 8 glioma stem cell (GSC) lines, together
      with the associated gene activation or repression patterns. In addition, we
      compared the genome-wide histone modification maps of GSC lines to those of
      astrocytes to identify unique gene activation or repression profiles in GSCs and
      astrocytes. We also identified a set of bivalent genes, which are genes that are
      associated with both H3K4me3 and H3K27me3 marks and are poised for action in
      embryonic stem cells. These bivalent genes are potential targets for inducing
      differentiation in glioblastoma (GBM) as a therapeutic approach. Finally, we
      identified SLC17A7 as a bivalent tumor suppressor gene in GBM, as it is down
      regulated at both the protein and RNA levels in GBM tissues compared with normal
      brain tissues, and it inhibits GBM cell proliferation, migration and invasion. 

PMID- 25749034
TI  - NPM/ALK mutants resistant to ASP3026 display variable sensitivity to alternative
      ALK inhibitors but succumb to the novel compound PF-06463922.
AB  - ALK is involved in the onset of several tumors. Crizotinib (XalkoriTM), a potent
      ALK inhibitor, represents the current front-line treatment for ALK+ NSCLC and
      shows great clinical efficacy. However, resistant disease often develops after
      initial response. ASP3026 is a novel second-generation ALK inhibitor with
      activity on crizotinib-resistant ALK-L1196M gatekeeper mutant. As resistance is
      likely to be a relevant hurdle for any drug, we sought to determine the
      resistance profile of ASP3026 in the context of NPM/ALK+ ALCL. We selected six
      ASP3026-resistant cell lines by culturing human ALCL cells in the presence of
      increasing concentrations of drug. The established resistant cell lines carry
      several point mutations in the ALK kinase domain (G1128S, C1156F, I1171N/T,
      F1174I, N1178H, E1210K and C1156F/D1203N were the most frequent) that are shown
      to confer resistance to ASP3026 in the Ba/F3 cell model. All mutants were
      profiled for cross-resistance against a panel of clinically relevant inhibitors
      including ceritinib, alectinib, crizotinib, AP26113 and PF-06463922. Finally, a
      genetically heterogeneous ASP3026-resistant cell line was exposed to second-line
      treatment simulations with all inhibitors. The population evolved according to
      relative sensitivity of its mutant subclones to the various drugs. Compound PF
      06463922 did not allow the outgrowth of any resistant clone, at non-toxic doses. 

PMID- 25749035
TI  - Glutamate and asparagine cataplerosis underlie glutamine addiction in melanoma.
AB  - Glutamine dependence is a prominent feature of cancer metabolism, and here we
      show that melanoma cells, irrespective of their oncogenic background, depend on
      glutamine for growth. A quantitative audit of how carbon from glutamine is used
      showed that TCA-cycle-derived glutamate is, in most melanoma cells, the major
      glutamine-derived cataplerotic output and product of glutaminolysis. In the
      absence of glutamine, TCA cycle metabolites were liable to depletion through
      aminotransferase-mediated alpha-ketoglutarate-to-glutamate conversion and
      glutamate secretion. Aspartate was an essential cataplerotic output, as melanoma
      cells demonstrated a limited capacity to salvage external aspartate. Also, the
      absence of asparagine increased the glutamine requirement, pointing to
      vulnerability in the aspartate-asparagine biosynthetic pathway within melanoma
      metabolism. In contrast to melanoma cells, melanocytes could grow in the absence
      of glutamine. Melanocytes use more glutamine for protein synthesis rather than
      secreting it as glutamate and are less prone to loss of glutamate and TCA cycle
      metabolites when starved of glutamine.

PMID- 25749036
TI  - FBXW7 suppresses epithelial-mesenchymal transition, stemness and metastatic
      potential of cholangiocarcinoma cells.
AB  - Epithelial-mesenchymal transition (EMT) plays a fundamental role in cancer
      metastasis. The ubiquitin ligase FBXW7, a general tumor suppressor in human
      cancer, has been implicated in diverse cellular processes, however, its role in
      cholangiocarcinoma (CCA) metastasis has not been identified. Here, we report a
      crucial role of FBXW7 in CCA metastasis by regulating EMT. Loss of FBXW7
      expression was detected in CCA cells and clinical specimens. Clinicopathological
      analysis revealed a close correlation between FBXW7 deficiency and metastasis,
      TNM stage and differentiation in intrahepatic CCA and perihilar CCA. Moreover,
      FBXW7 silencing in CCA cells dramatically promoted EMT, stem-like capacity and
      metastasis both in vitro and in vivo. Conversely, FBXW7 overexpression attenuated
      these processes. Mechanistically, treatment with rapamycin, a mTOR inhibitor,
      inhibited EMT, stem-like capacity and metastasis induced by FBXW7 silencing both
      in vitro and in vivo. Furthermore, the expression of EMT regulating transcription
      factors, snail, slug and ZEB1, were also decreased markedly with rapamycin
      treatment. In addition, silencing ZEB1 inhibited EMT and metastasis of both CCA
      cells and FBXW7 deficient CCA cells, which implicated the potential role of ZEB1
      in FBXW7/mTOR signaling pathway related CCA metastasis. In conclusion, our
      findings defined a pivotal function of FBXW7 in CCA metastasis by regulating EMT.

PMID- 25749037
TI  - Autophagy protects against dasatinib-induced hepatotoxicity via p38 signaling.
AB  - Liver dysfunction is a common side effect associated with the treatment of
      dasatinib and its mechanism is poorly understood. Autophagy has been thought to
      be a potent survival or death factor for liver dysfunction, which may shed the
      light on a novel strategy for the intervention of hepatotoxicity caused by
      dasatinib. In this study, we show for the first time that autophagy is induced,
      which is consistent with the formation of liver damage. Autophagy inhibition
      exacerbated dasatinib-induced liver failure, suggesting that autophagy acted as a
      self-defense mechanism to promote survival. Oxidative stress has been shown to be
      an important stimulus for autophagy and hepatotoxicity. Interestingly, dasatinib
      increased the activity of p38, which is a critical modulator of the oxidative
      stress related to liver injury and autophagy. p38 silencing significantly blocked
      LC3-II induction and p62 reduction by dasatinib, which was accompanied by
      increased caspase-3 and PARP cleavage, indicating that autophagy alleviated
      dasatinib-induced hepatotoxicity via p38 signaling. Finally, the p38 agonist
      isoproterenol hydrochloride (ISO) alleviated dasatinib-induced liver failure by
      enhancing autophagy without affecting the anticancer activity of dasatinib. Thus,
      this study revealed that p38-activated autophagy promoted survival during liver
      injury, which may provide novel approaches for managing the clinical applications
      of dasatinib. 

PMID- 25749038
TI  - Targeting WISP1 to sensitize esophageal squamous cell carcinoma to irradiation.
AB  - Radiotherapy is a primary treatment modality for esophageal squamous cell
      carcinoma (ESCC). However, most of patients benefited little from radiotherapy
      due to refractory radioresistance. We found that WISP1, a downstream target gene
      of Wnt/beta-catenin pathway, was re-expressed in 67.3% of ESCC patients as an
      oncofetal gene. Expression of WISP1 predicted prognosis of ESCC patients treated
      with radiotherapy. Overall survival in WISP1-positive patients was significantly
      poorer than in WISP1-negative patients. Serum concentration of WISP1 after
      radiotherapy reversely correlated with relapse-free survival. Gain and loss of
      function studies confirmed that WISP1 mediated radioresistance both in esophageal
      squamous cancer cells and in xenograft tumor models. Further studies revealed
      that WISP1 contributed to radioresistance primarily by repressing irradiation
      induced DNA damage and activating PI3K kinase. LncRNA BOKAS was up-regulated
      following radiation and promoted WISP1 expression and resultant radioresistance.
      Furthermore, WISP1 facilitated its own expression in response to radiation,
      creating a positive feedback loop and increased radioresistance. Our study
      revealed WISP1 as a potential target to overcome radioresistance in ESCC.

PMID- 25749039
TI  - Recurrent SKIL-activating rearrangements in ETS-negative prostate cancer.
AB  - Prostate cancer is the third most common cause of male cancer death in developed
      countries, and one of the most comprehensively characterized human cancers.
      Roughly 60% of prostate cancers harbor gene fusions that juxtapose ETS-family
      transcription factors with androgen regulated promoters. A second subtype,
      characterized by SPINK1 overexpression, accounts for 15% of prostate cancers.
      Here we report the discovery of a new prostate cancer subtype characterized by
      rearrangements juxtaposing the SMAD inhibitor SKIL with androgen regulated
      promoters, leading to increased SKIL expression. SKIL fusions were found in 6 of
      540 (1.1%) prostate cancers and 1 of 27 (3.7%) cell lines and xenografts. 6 of 7
      SKIL-positive cancers were negative for ETS overexpression, suggesting mutual
      exclusivity with ETS fusions. SKIL knockdown led to growth arrest in PC-3 and
      LNCaP cell line models of prostate cancer, and its overexpression led to
      increased invasiveness in RWPE-1 cells. The role of SKIL as a prostate cancer
      oncogene lends support to recent studies on the role of TGF-beta signaling as a
      rate-limiting step in prostate cancer progression. Our findings highlight SKIL as
      an oncogene and potential therapeutic target in 1-2% of prostate cancers,
      amounting to an estimated 10,000 cancer diagnoses per year worldwide. 

PMID- 25749040
TI  - ROCK inhibition promotes microtentacles that enhance reattachment of breast
      cancer cells.
AB  - The presence of circulating tumor cells (CTCs) in blood predicts poor patient
      outcome and CTC frequency is correlated with higher risk of metastasis. Recently
      discovered, novel microtubule-based structures, microtentacles, can enhance
      reattachment of CTCs to the vasculature. Microtentacles are highly dynamic
      membrane protrusions formed in detached cells and occur when physical forces
      generated by the outwardly expanding microtubules overcome the contractile force
      of the actin cortex. Rho-associated kinase (ROCK) is a major regulator of
      actomyosin contractility and Rho/ROCK over-activation is implicated in tumor
      metastasis. ROCK inhibitors are gaining popularity as potential cancer
      therapeutics based on their success in reducing adherent tumor cell migration and
      invasion. However, the effect of ROCK inhibition on detached cells in circulation
      is largely unknown. In this study, we use breast tumor cells in suspension to
      mimic detached CTCs and show that destabilizing the actin cortex through ROCK
      inhibition in suspended cells promotes the formation of microtentacles and
      enhances reattachment of cells from suspension. Conversely, increasing actomyosin
      contraction by Rho over-activation reduces microtentacle frequency and
      reattachment. Although ROCK inhibitors may be effective in reducing adherent
      tumor cell behavior, our results indicate that they could inadvertently increase
      metastatic potential of non-adherent CTCs by increasing their reattachment
      efficacy. 

PMID- 25749041
TI  - Efficacy and safety of decitabine in combination with G-CSF, low-dose cytarabine
      and aclarubicin in newly diagnosed elderly patients with acute myeloid leukemia.
AB  - PURPOSE: This prospective phase II, open label, study was designed to assess the
      efficacy and safety of D-CAG induction treatment for elderly patients with newly
      diagnosed AML. EXPERIMENTAL DESIGN: All patients in this study were treated with
      decitabine of 15 mg/m2 for 5 days and G-CSF for priming, in combination with
      cytarabine of 10-mg/m2 q12h for 7 days and aclarubicin of 10 mg/day for 4 days (D
      CAG). RESULTS: Among 85 evaluable patients, overall response rate (ORR) and
      complete remission (CR) were 82.4% and 64.7%, respectively, after 1 cycle of
      therapy. The ORR in patients aged <70 years was 83.0% and 81.6% in patients aged
      >=70 years. There was a significantly longer median overall survival (OS) in
      patients with response (16 months) than in those without response (7 months, p<
      0.0001). The OS for patients aged >=70 years and 60-69 years was 10 months and 12
      months, respectively (p=0.4994). The two-year OS probability was 19.2% and the
      twenty-month survival rate was 33.8%. Induction mortality of D-CAG treated
      elderly patients with AML is 4.4%. CONCLUSION: D-CAG regimen was well tolerated
      and showed a promising clinic efficacy in elderly patients with AML (>=70 years).

PMID- 25749042
TI  - Antibody response to BK polyomavirus as a prognostic biomarker and potential
      therapeutic target in prostate cancer.
AB  - Infectious agents, including the BK polyomavirus (BKPyV), have been proposed as
      important inflammatory pathogens in prostate cancer. Here, we evaluated whether
      the preoperative antibody response to BKPyV large T antigen (LTag) and viral
      capsid protein 1 (VP1) was associated with the risk of biochemical recurrence in
      226 patients undergoing radical prostatectomy for primary prostate cancer.
      Essentially, the multivariate Cox regression analysis revealed that preoperative
      seropositivity to BKPyV LTag significantly reduced the risk of biochemical
      recurrence, independently of established predictors of biochemical recurrence
      such as tumor stage, Gleason score and surgical margin status. The predictive
      accuracy of the regression model was denotatively increased by the inclusion of
      the BKPyV LTag serostatus. In contrast, the VP1 serostatus was of no prognostic
      value. Finally, the BKPyV LTag serostatus was associated with a peculiar cytokine
      gene expression profile upon assessment of the cellular immune response elicited
      by LTag. Taken together, our findings suggest that the BKPyV LTag serology may
      serve as a prognostic factor in prostate cancer. If validated in additional
      studies, this biomarker may allow for better treatment decisions after radical
      prostatectomy. Finally, the favorable outcome of LTag seropositive patients may
      provide a potential opportunity for novel therapeutic approaches targeting a
      viral antigen. 

PMID- 25749043
TI  - Coexpression analysis of CD133 and CD44 identifies proneural and mesenchymal
      subtypes of glioblastoma multiforme.
AB  - Accumulating evidence suggests that the stem cell markers CD133 and CD44 indicate
      molecular subtype in Glioblastoma Multiforme (GBM). Gene coexpression analysis of
      The Cancer Genome Atlas GBM dataset was undertaken to compare markers of the
      Glioblastoma Stem-Progenitor Cell (GSPC) phenotype. Pearson correlation
      identified genes coexpressed with stem cell markers, which were then used to
      build a gene signature that classifies patients based on a CD133 coexpression
      module signature (CD133-M) or CD44-M subtype. CD133-M tumors were enriched for
      the Proneural (PN) GBM subtype compared to Mesenchymal (MES) subtype for CD44-M
      tumors. Gene set enrichment identified DNA replication/cell cycle genes in the
      CD133-M and invasion/migration in CD44-M, while functional experiments showed
      enhanced cellular growth in CD133 expressing cells and enhanced invasion in cells
      expressing CD44. As with the 4 major molecular subtypes of GBM, there was no long
      term survival difference between CD44-M and CD133-M patients, although CD44-M
      patients responded better to temozolomide while CD133-M patients benefited from
      radiotherapy. The use of a targeted coexpression approach to predict functional
      properties of surface marker expressing cells is novel, and in the context of
      GBM, supports accumulating evidence that CD133 and CD44 protein marker expression
      correlates with molecular subtype. 

PMID- 25749044
TI  - Function of phosphorylation of NF-kB p65 ser536 in prostate cancer oncogenesis.
AB  - Majority of prostate cancer (PCa) patients carry TMPRSS2/ERG (T/E) fusion genes
      and there has been tremendous interest in understanding how the T/E fusion may
      promote progression of PCa. We showed that T/E fusion can activate NF-kB pathway
      by increasing phosphorylation of NF-kB p65 Ser536 (p536), but the function of
      p536 has never been studied in PCa. We report here that active p536 can
      significantly increase cell motility and transform PNT1a cells (an immortalized
      normal cell line), suggesting p536 plays a critical role in promoting PCa
      tumorigenesis. We have discovered a set of p536 regulated genes, among which we
      validated the regulation of CCL2 by p536. Based on all evidence, we favor that
      T/E fusion, NF-kB p536 and CCL2 form a signaling chain. Finally, PNT1a cells (not
      tumorigenic) can form tumors in SCID mice when overexpressing of either wild type
      or active p65 in the presence of activated AKT, demonstrating synergistic
      activities of NF-kB and AKT signals in promoting PCa tumorigenesis. These
      findings indicate that combination therapies targeting T/E fusion, NF-kB, CCL2
      and/or AKT pathways may have efficacy in T/E fusion gene expressing PCa. If
      successful, such targeted therapy will benefit more than half of PCa patients who
      carry T/E fusions. 

PMID- 25749045
TI  - Mechanistic rationale for MCL1 inhibition during androgen deprivation therapy.
AB  - Androgen deprivation therapy induces apoptosis or cell cycle arrest in prostate
      cancer (PCa) cells. Here we set out to analyze whether MCL1, a known mediator of
      chemotherapy resistance regulates the cellular response to androgen withdrawal.
      Analysis of MCL1 protein and mRNA expression in PCa tissue and primary cell
      culture specimens of luminal and basal origin, respectively, reveals higher
      expression in cancerous tissue compared to benign origin. Using PCa cellular
      models in vitro and in vivo we show that MCL1 expression is upregulated in
      androgen-deprived PCa cells. Regulation of MCL1 through the AR signaling axis is
      indirectly mediated via a cell cycle-dependent mechanism. Using constructs
      downregulating or overexpressing MCL1 we demonstrate that expression of MCL1
      prevents induction of apoptosis when PCa cells are grown under steroid-deprived
      conditions. The BH3-mimetic Obatoclax induces apoptosis and decreases MCL1
      expression in androgen-sensitive PCa cells, while castration-resistant PCa cells
      are less sensitive and react with an upregulation of MCL1 expression. Synergistic
      effects of Obatoclax with androgen receptor inactivation can be observed.
      Moreover, clonogenicity of primary basal PCa cells is efficiently inhibited by
      Obatoclax. Altogether, our results suggest that MCL1 is a key molecule deciding
      over the fate of PCa cells upon inactivation of androgen receptor signaling. 

PMID- 25749046
TI  - Targeting argininosuccinate synthetase negative melanomas using combination of
      arginine degrading enzyme and cisplatin.
AB  - Loss of argininosuccinate synthetase (ASS) expression in melanoma makes these
      tumor cells vulnerable to arginine deprivation. Pegylated arginine deiminase (ADI
      PEG20) which degrades arginine to citrulline and ammonia has been used clinically
      and partial responses and stable disease have been noted with minimal toxicity.
      In order to improve the therapeutic efficacy of ADI-PEG20, we have combined ADI
      PEG20 with a DNA damaging agent, cisplatin. We have shown that the combination of
      the two drugs together significantly improved the therapeutic efficacy when
      compared to ADI-PEG20 alone or cisplatin alone in 4 melanoma cell lines,
      regardless of their BRAF mutation. In-vivo study also exhibited the same effect
      as in-vitro with no added toxicity to either agent alone. The underlying
      mechanism is complex, but increased DNA damage upon arginine deprivation due to
      decreased DNA repair proteins, FANCD2, ATM, and CHK1/2 most likely leads to
      increased apoptosis. This action is further intensified by increased proapoptotic
      protein, NOXA, and decreased antiapoptotic proteins, SURVIVIN, BCL2 and XIAP. The
      autophagic process which protects cells from apoptosis upon ADI-PEG20 treatment
      also dampens upon cisplatin administration. Thus, the combination of arginine
      deprivation and cisplatin function in concert to kill tumor cells which do not
      express ASS without added toxicity to normal cells. 

PMID- 25749047
TI  - Free ISG15 triggers an antitumor immune response against breast cancer: a new
      perspective.
AB  - Interferon-Stimulated Gene 15 (ISG15), an antagonist of the canonical ubiquitin
      pathway, is frequently overexpressed in various cancers. In cancer cells, ISG15
      is detected as free (intracellular) and conjugated to cellular proteins
      (ISGylation). Free ISG15 is also secreted into the extracellular milieu.
      ISGylation has protumor functions and extracellular free ISG15 has
      immunomodulatory properties in vitro. Therefore, whether ISG15 is a tumor
      suppressor or tumor promoter in vivo remains controversial. The current study
      aimed to clarify the role of free ISG15 in tumorigenesis. Breast cancer cells
      stably expressing control, ISG15, and UbcH8 (ISG15-specific E2 ligase) shRNAs
      were used to assess the immunoregulatory and antitumor function of free ISG15 in
      cell culture (in vitro) and in nude mice (in vivo). We show that extracellular
      free ISG15 suppresses breast tumor growth and increases NK cell infiltration into
      xenografted breast tumors in nude mice, and intracellular free ISG15 enhances
      major histocompatibility complex (MHC) class I surface expression in breast
      cancer cells. We conclude that free ISG15 may have antitumor and immunoregulatory
      function in vivo. These findings provides the basis for developing strategies to
      increase systemic levels of free ISG15 to treat cancer patients overexpressing
      the ISG15 pathway. 

PMID- 25749048
TI  - A standardized autopsy procurement allows for the comprehensive study of DIPG
      biology.
AB  - Diffuse intrinsic pontine glioma (DIPG) is one of the least understood and most
      deadly childhood cancers. Historically, there has been a paucity of DIPG
      specimens for molecular analysis. However, due to the generous participation of
      DIPG families in programs for postmortem specimen donation, there has been a
      recent surge in molecular analysis of newly available tumor specimens.
      Collaborative efforts to share data and tumor specimens have resulted in rapid
      discoveries in other pediatric brain tumors, such as medulloblastoma, and
      therefore have the potential to shed light on the biology of DIPG. Given the
      generous gift of postmortem tissue donation from DIPG patients, there is a need
      for standardized postmortem specimen accrual to facilitate rapid and effective
      multi-institutional molecular studies.We developed and implemented an autopsy
      protocol for rapid procurement, documenting and storing these specimens. Sixteen
      autopsies were performed throughout the United States and Canada and processed
      using a standard protocol and inventory method, including specimen imaging,
      fixation, snap freezing, orthotopic injection, or preservation. This allowed for
      comparative clinical and biological studies of rare postmortem DIPG tissue
      specimens, generation of in vivo and in vitro models of DIPG, and detailed
      records to facilitate collaborative analysis. 

PMID- 25749049
TI  - Multiple mechanisms of MYCN dysregulation in Wilms tumour.
AB  - Genomic gain of the proto-oncogene transcription factor gene MYCN is associated
      with poor prognosis in several childhood cancers. Here we present a comprehensive
      copy number analysis of MYCN in Wilms tumour (WT), demonstrating that gain of
      this gene is associated with anaplasia and with poorer relapse-free and overall
      survival, independent of histology. Using whole exome and gene-specific
      sequencing, together with methylation and expression profiling, we show that MYCN
      is targeted by other mechanisms, including a recurrent somatic mutation, P44L,
      and specific DNA hypomethylation events associated with MYCN overexpression in
      tumours with high risk histologies. We describe parallel evolution of genomic
      copy number gain and point mutation of MYCN in the contralateral tumours of a
      remarkable bilateral case in which independent contralateral mutations of TP53
      also evolve over time. We report a second bilateral case in which MYCN gain is a
      germline aberration. Our results suggest a significant role for MYCN
      dysregulation in the molecular biology of Wilms tumour. We conclude that MYCN
      gain is prognostically significant, and suggest that the novel P44L somatic
      variant is likely to be an activating mutation. 

PMID- 25749050
TI  - Differences and similarities in rheumatology specialty training programmes across
      European countries.
AB  - OBJECTIVES: To analyse the similarities and discrepancies between the official
      rheumatology specialty training programmes across Europe. METHODS: A steering
      committee defined the main aspects of training to be assessed. In 2013, the
      rheumatology official training programmes were reviewed for each of the European
      League Against Rheumatism (EULAR) countries and two local physicians
      independently extracted data on the structure of training, included competencies
      and assessments performed. Analyses were descriptive. RESULTS: 41 of the 45 EULAR
      countries currently provide specialist training in rheumatology; in the remaining
      four rheumatologists are trained abroad. 36 (88%) had a single national
      curriculum, one country had two national curricula and four had only local or
      university-specific curricula. The mean length of training programmes in
      rheumatology was 45 (SD 19) months, ranging between 3 and 72 months. General
      internal medicine training was mandatory in 40 (98%) countries, and was performed
      prior to and/or during the rheumatology training programme (mean length: 33 (19)
      months). 33 (80%) countries had a formal final examination. CONCLUSIONS: Most
      European countries provide training in rheumatology, but the length, structure,
      contents and assessments of these training programmes are quite heterogeneous. In
      order to promote excellence in standards of care and to support physicians'
      mobility, a certain degree of harmonisation should be encouraged.

PMID- 25749051
TI  - Is chondroitin sulfate plus glucosamine superior to placebo in the treatment of
      knee osteoarthritis?

PMID- 25749052
TI  - Conformational diversity and the emergence of sequence signatures during
      evolution.
AB  - Proteins' native structure is an ensemble of conformers in equilibrium, including
      all their respective functional states and intermediates. The induced-fit first
      and the pre-equilibrium theories later, described how structural changes are
      required to explain the allosteric and cooperative behaviours in proteins, which
      are key to protein function. The conformational ensemble concept has become a key
      tool in explaining an endless list of essential protein properties such as
      function, enzyme and antibody promiscuity, signal transduction, protein-protein
      recognition, origin of diseases, origin of new protein functions, evolutionary
      rate and order-disorder transitions, among others. Conformational diversity is
      encoded by the amino acid sequence and such a signature can be evidenced through
      evolutionary studies as evolutionary rate, conservation and coevolution. 

PMID- 25749053
TI  - Valproic acid attenuates acute lung injury induced by ischemia-reperfusion in
      rats.
AB  - BACKGROUND: Evidence reveals that histone deacetylase (HDAC) inhibition has
      potential for the treatment of inflammatory diseases. The protective effect of
      HDAC inhibition involves multiple mechanisms. Heme oxygenase-1 (HO-1) is
      protective in lung injury as a key regulator of antioxidant response. The authors
      examined whether HDAC inhibition provided protection against ischemia-reperfusion
      (I/R) lung injury in rats by up-regulating HO-1 activity. METHODS: Acute lung
      injury was induced by producing 40 min of ischemia followed by 60 min of
      reperfusion in isolated perfused rat lungs. The rats were randomly allotted to
      control group, I/R group, or I/R + valproic acid (VPA) group with or without an
      HO-1 activity inhibitor (zinc protoporphyrin IX) (n = 6 per group). RESULTS: I/R
      caused significant increases in the lung edema, pulmonary arterial pressure, lung
      injury scores, tumor necrosis factor-alpha, and cytokine-induced neutrophil
      chemoattractant-1 concentrations in bronchoalveolar lavage fluid. Malondialdehyde
      levels, carbonyl contents, and myeloperoxidase-positive cells in lung tissue were
      also significantly increased. I/R stimulated the degradation of inhibitor of
      nuclear factor-kappaB-alpha, nuclear translocation of nuclear factor-kappaB, and
      up-regulation of HO-1 activity. Furthermore, I/R decreased B-cell lymphoma-2,
      heat shock protein 70, acetylated histone H3 protein expression, and increased
      the caspase-3 activity in the rat lungs. In contrast, VPA treatment significantly
      attenuated all the parameters of lung injury, oxidative stress, apoptosis, and
      inflammation. In addition, VPA treatment also enhanced HO-1 activity. Treatment
      with zinc protoporphyrin IX blocked the protective effect of VPA. CONCLUSIONS:
      VPA protected against I/R-induced lung injury. The protective mechanism may be
      partly due to enhanced HO-1 activity following HDAC inhibition.

PMID- 25749054
TI  - Commercially Available Rapid Methods for Detection of Selected Food-borne
      Pathogens.
AB  - Generally, the enumeration and isolation of food-borne pathogens is performed
      using culture-dependent methods. These methods are sensitive, inexpensive, and
      provide both qualitative and quantitative assessment of the microorganisms
      present in a sample, but these are time-consuming. For this reason, researchers
      are developing new techniques that allow detection of food pathogens in shorter
      period of time. This review identifies commercially available methods for rapid
      detection and quantification of Listeria monocytogenes, Salmonella spp.,
      Staphylococcus aureus, and Shiga toxin-producing Escherichia coli in food
      samples. Three categories are discussed: immunologically based methods, nucleic
      acid-based assays, and biosensors. This review describes the basic mechanism and
      capabilities of each method, discusses the difficulties of choosing the most
      convenient method, and provides an overview of the future challenges for the
      technology for rapid detection of microorganisms. 

PMID- 25749055
TI  - High dysphagia: a case report.

PMID- 25749056
TI  - End of the debate on hormonal contraception and HIV risk?

PMID- 25749057
TI  - Shortening treatment of tuberculosis: lessons from fluoroquinolone trials.

PMID- 25749058
TI  - Climate change and infectious disease: time for a new normal?

PMID- 25749059
TI  - Brucellar aortitis and brucellar spondylitis.

PMID- 25749060
TI  - Severe fever with thrombocytopenia syndrome in China.

PMID- 25749061
TI  - Ebola: lessons learned from HIV and tuberculosis epidemics.

PMID- 25749062
TI  - Ebola: between mathematics and reality.

PMID- 25749063
TI  - Modelling the effect of early detection of Ebola.

PMID- 25749064
TI  - Community-based care of Ebola virus disease in west Africa.

PMID- 25749065
TI  - Prioritising clean water and sanitation.

PMID- 25749066
TI  - International Sepsis Forum 2014.

PMID- 25749067
TI  - India fights rabies.

PMID- 25749071
TI  - Time-Related Changes in Yield and Harms of Screening Breast Magnetic Resonance
      Imaging.
AB  - PURPOSE: Breast magnetic resonance imaging (MRI) is accepted as a useful adjunct
      to screening mammography for women at high risk for breast cancer. Nevertheless,
      concerns about false-positive findings remain, and data about MRI harms and
      yields are limited. The aim of this study was to quantify harms and yields of
      breast MRI over time in a large series of patients. METHODS: A retrospective
      review was performed of patients at increased risk for breast cancer who
      underwent annual screening digital mammography and MRI from 2007 to 2013. Harms
      were defined as events not producing a breast cancer diagnosis (ultrasonography
      [US], imaging-guided core or surgical biopsy procedure, recommendation for short
      term follow-up, or a combination). RESULTS: Of 350 high-risk patients offered MRI
      screening, 320 underwent 757 screening MRI procedures over time. The median age
      at the first MRI was 48 years. All patients met American Cancer Society criteria
      for annual screening breast MRI. Total harms were highest with the first MRI
      procedure and decreased with subsequent MRI screening. Of 75 biopsy procedures
      performed, including 58 US- or MRI-guided core biopsy procedures and 17 surgical
      biopsy procedures, 6 specimens were found to be malignant, including 2 resulting
      from biopsy procedures performed based on findings from the first MRI scan, 0
      from the second MRI scan, 3 from the third MRI scan, and 1 from the fourth MRI
      scan. CONCLUSION: Among women followed with screening MRI, the number of harms
      was shown to decrease over time. Breast cancer continued to be detected in MRI
      studies performed over time. This study demonstrates the utility of MRI screening
      performed over time in high-risk women.

PMID- 25749072
TI  - Efficacy of Scalp Cooling in Preventing Chemotherapy-Induced Alopecia in Breast
      Cancer Patients Receiving Adjuvant Docetaxel and Cyclophosphamide Chemotherapy.
AB  - BACKGROUND: Chemotherapy-induced alopecia (CIA) is a distressing adverse effect
      of many chemotherapy agents. The TC (docetaxel [Taxotere] and cyclophosphamide)
      chemotherapy regimen is typically associated with complete alopecia. Scalp
      cooling with cold caps has been reported to minimize or prevent CIA. We conducted
      a prospective study to assess efficacy of scalp cooling in preventing CIA among
      women receiving adjuvant TC chemotherapy for breast cancer. METHODS: Women at the
      Weill Cornell Breast Center who independently elected to use scalp cooling with
      cold caps during adjuvant TC chemotherapy were asked to participate. Degree of
      hair loss was assessed by a single practitioner using Dean's alopecia scale
      (grade 1/excellent [< 25% hair loss], grade 2/good [25%-50% hair loss], grade
      3/moderate [50%-75% hair loss], grade 4/poor [> 75% hair loss]), by digital
      photographs, and by patient self-report of hair thinning or the need to wear a
      wig/head covering, or both. Assessments were made before each chemotherapy
      treatment and at follow-up visits between 3 weeks and 3 months after completion
      of chemotherapy. RESULTS: Of 20 evaluable patients, 10% reported a need to wear a
      wig/head covering at the follow-up visit. Dean's alopecia score was excellent for
      65% of patients, good for 25% of patients, and moderate or poor for 10% of
      patients. The majority of patients reported hair thinning after every
      chemotherapy cycle. No patient discontinued therapy because of an intolerance to
      cold caps. CONCLUSION: Scalp cooling with cold caps appears to be effective in
      preventing CIA among the majority of women undergoing treatment with TC
      chemotherapy.

PMID- 25749073
TI  - Influence of excipients on solubility and dissolution of pharmaceuticals.
AB  - In this work, solubilities and dissolution profiles of the active pharmaceutical
      ingredients (APIs) indomethacin and naproxen were measured in water in the
      presence of one excipient out of polyethylene glycol (PEG) 2000, 6000 and 12000,
      polyvinylpyrrolidone (PVP) K 25 and mannitol. It was found that the solubility of
      indomethacin and naproxen was increased with an addition of the selected
      excipients, which was also predicted by the perturbed-chain statistical
      associating fluid theory (PC-SAFT). The two-step chemical-potential-gradient
      model was applied to investigate the dissolution mechanism of indomethacin and
      naproxen in water in the presence of the excipient. It was found that the
      dissolution mechanisms of indomethacin and naproxen were changed by the presence
      of excipients. Although the solubility of the API was increased by the addition
      of excipients, the dissolution rate of the API was decreased in some cases. This
      was mainly due to the combination of the molecular interactions between the API
      and the polymer with the influence of the excipients on the kinetic part (rate
      constant of the surface reaction or diffusion of the API or both) of API
      dissolution as function of PEG molar mass as well as of the API type. Based upon
      the determined rate constants, the dissolution profiles were modeled with a high
      accuracy compared with the experimental data.

PMID- 25749074
TI  - Time-course of performance changes and underlying mechanisms during and after
      repetitive moderately weight-loaded knee extensions.
AB  - The purpose of this study was to investigate the mechanisms of fatigue
      development induced by isoload (IL) fatiguing knee extensions. Nine physically
      active males (age=23+/-2years, height=179+/-7cm, mass=76+/-7kg) performed
      repetitive ballistic knee extensions at 30% of the isometric maximal voluntary
      peak torque. Fatigue development was assessed throughout the fatiguing exercise
      by quantifying changes in peak torque, agonist and antagonist electromyographic
      activity (EMG) and torque- and EMG-angle relationships. Before and after the
      fatiguing exercise, isometric maximal voluntary contractions were performed to
      measure peak torque (MVIC torque), voluntary activation (VA) and resting twitch
      torque. IL peak torque decreased from the middle of the fatiguing exercise while
      the agonist and antagonist EMG amplitude increased consistently during the entire
      exercise (P<.005). The pattern of the torque-angle relationship changed with
      fatigue (P<.005) reflecting a change in torque production strategy even if the
      EMG-angle relationships were not modified. Post-exercise testing revealed a
      decrease in MVIC torque (-31%; P<.005). VA was unchanged (P=.60) while the
      resting twitch torque was impaired to a great extent (-46%; P<.005) suggesting
      that local muscular mechanisms but not neural drive were altered during single
      joint IL fatiguing task. 

PMID- 25749075
TI  - Vascular normalization induced by sinomenine hydrochloride results in suppressed
      mammary tumor growth and metastasis.
AB  - Solid tumor vasculature is characterized by structural and functional abnormality
      and results in a hostile tumor microenvironment that mediates several deleterious
      aspects of tumor behavior. Sinomenine is an alkaloid extracted from the Chinese
      medicinal plant, Sinomenium acutum, which has been utilized to treat rheumatism
      in China for over 2000 years. Though sinomenine has been demonstrated to mediate
      a wide range of pharmacological actions, few studies have focused on its effect
      on tumor vasculature. We showed here that intraperitoneally administration of 100
      mg/kg sinomenine hydrochloride (SH, the hydrochloride chemical form of
      sinomenine) in two orthotopic mouse breast cancer models for 14 days, delayed
      mammary tumor growth and decreased metastasis by inducing vascular maturity and
      enhancing tumor perfusion, while improving chemotherapy and tumor immunity. The
      effects of SH on tumor vessels were caused in part by its capability to restore
      the balance between pro-angiogenic factor (bFGF) and anti-angiogenic factor
      (PF4). However 200 mg/kg SH didn't exhibit the similar inhibitory effect on tumor
      progression due to the immunosuppressive microenvironment caused by excessive
      vessel pruning, G-CSF upregulation, and GM-CSF downregulation. Altogether, our
      findings suggest that SH induced vasculature normalization contributes to its
      anti-tumor and anti-metastasis effect on breast cancer at certain dosage. 

PMID- 25749077
TI  - Clinical and histologic outcomes of socket grafting after flapless tooth
      extraction: a systematic review of randomized controlled clinical trials.
AB  - STATEMENT OF PROBLEM: Several biomaterials and techniques have been reported for
      socket grafting and alveolar ridge preservation. However, the evidence for
      clinical and histologic outcomes for socket grafting with different types of
      materials in flapless extraction is not clear. PURPOSE: The purpose of this
      systematic review was to analyze the outcomes of a socket grafting procedure
      performed with flapless extraction of teeth in order to determine which graft
      material results in the least loss of socket dimensions, the maximum amount of
      vital bone, the least remnant graft material, and the least amount of connective
      tissue after a minimum of 12 weeks of healing. Secondary outcomes, including the
      predictability of regenerating deficient buccal bone, necessity of barrier
      membranes, and coverage with autogenous soft tissue graft, were also evaluated.
      MATERIAL AND METHODS: An electronic search for articles in the English-language
      literature was performed independently by multiple investigators using a
      systematic search process with the PubMed search engine. After applying
      predetermined inclusion and exclusion criteria, the final list of randomized
      controlled clinical trials (RCTs) for flapless extraction and socket grafting was
      analyzed to derive results for the various objectives of the study. RESULTS: The
      initial electronic search resulted in 2898 titles. The systematic application of
      inclusion and exclusion criteria resulted in 32 RCTs studying 1354 sockets, which
      addressed the clinical and histologic outcomes of flapless extraction with socket
      grafting and provided dimensional and histologic information at or beyond the 12
      week reentry period. From these RCTs, the mean loss of buccolingual width at the
      ridge crest was lowest for xenografts (1.3 mm), followed by allografts (1.63 mm),
      alloplasts (2.13 mm), and sockets without any socket grafting (2.79 mm). Only 3
      studies reported on loss of width at 3 mm below the ridge crest. The mean loss of
      buccal wall height from the ridge crest was lowest for xenografts (0.57 mm) and
      allografts (0.58 mm), followed by alloplasts (0.77 mm) and sockets without any
      grafting (1.74 mm). The mean histologic outcomes at or beyond the 12-week reentry
      period revealed the highest vital bone content for sockets grafted with
      alloplasts (45.53%), followed by sockets with no graft material (41.07%),
      xenografts (35.72%), and allografts (29.93%). The amount of remnant graft
      material was highest for sockets grafted with allografts (21.75%), followed by
      xenografts (19.3%) and alloplasts (13.67%). The highest connective tissue content
      at the time of reentry was seen for sockets with no grafting (52.53%), followed
      by allografts (51.03%), xenografts (44.42%), and alloplast (38.39%). Data for new
      and emerging biomaterials such as cell therapy and tissue regenerative materials
      were not amenable to calculations because of biomaterial heterogeneity and small
      sample sizes. CONCLUSIONS: After flapless extraction of teeth, and using a
      minimum healing period of 12 weeks as a temporal measure, xenografts and
      allografts resulted in the least loss of socket dimensions compared to alloplasts
      or sockets with no grafting. Histologic outcomes after a minimum of 12 weeks of
      healing showed that sockets grafted with alloplasts had the maximum amount of
      vital bone and the least amount of remnant graft material and remnant connective
      tissue. There is a limited but emerging body of evidence for the predictable
      regeneration of deficient buccal bone with socket grafting materials, need for
      barrier membranes, use of tissue engineering, and use of autogenous soft tissue
      grafts from the palate to cover the socket.

PMID- 25749076
TI  - Complex genomic rearrangements at the PLP1 locus include triplication and
      quadruplication.
AB  - Inverted repeats (IRs) can facilitate structural variation as crucibles of
      genomic rearrangement. Complex duplication-inverted triplication-duplication (DUP
      TRP/INV-DUP) rearrangements that contain breakpoint junctions within IRs have
      been recently associated with both MECP2 duplication syndrome (MIM#300260) and
      Pelizaeus-Merzbacher disease (PMD, MIM#312080). We investigated 17 unrelated PMD
      subjects with copy number gains at the PLP1 locus including triplication and
      quadruplication of specific genomic intervals-16/17 were found to have a DUP
      TRP/INV-DUP rearrangement product. An IR distal to PLP1 facilitates DUP-TRP/INV
      DUP formation as well as an inversion structural variation found frequently
      amongst normal individuals. We show that a homology-or homeology-driven
      replicative mechanism of DNA repair can apparently mediate template switches
      within stretches of microhomology. Moreover, we provide evidence that
      quadruplication and potentially higher order amplification of a genomic interval
      can occur in a manner consistent with rolling circle amplification as predicted
      by the microhomology-mediated break induced replication (MMBIR) model. 

PMID- 25749078
TI  - Airborne-particle abrasion parameters on the quality of titanium-ceramic bonds.
AB  - STATEMENT OF PROBLEM: Airborne-particle abrasion of titanium is a clinically
      acceptable method of surface preparation. It is crucial to know the effectiveness
      of bond strength between the metal substructure and the veneering ceramics after
      this kind of surface treatment. PURPOSE: The purpose of this study was to
      determine how the particle size of the abrasive material and pressure affected
      treated surfaces and the strength of titanium-ceramic bonds. MATERIAL AND
      METHODS: Disks made of titanium (Tritan CpTi grade 1, Dentaurum, 99.5% Ti) were
      treated in an airborne-particle abrasion process with 50, 110, and 250 MUm
      aluminum oxide (Al2O3) at pressures of 0.2, 0.4, and 0.6 MPa. To characterize the
      treated surfaces, the following values were measured: roughness, free surface
      energy, and the quantity of abrasive particles attached to the surface.
      Subsequently, the strength of the metal-ceramic bond was determined. Apart from
      the strength tests, fractures were observed to determine the character and
      fracture location in the course of the strength tests. The results of the
      experiment were analyzed with 2-way ANOVA and the Tukey HSD test (alpha=.05).
      RESULTS: Both the pressure and the particle size of Al2O3 used in the airborne
      particle abrasion affected the strength of the titanium-ceramic bond (P<.05). A
      statistically significant difference was found between the group subjected to
      airborne-particle abrasion under a pressure of 0.4 MPa with 110-MUm Al2O3
      particles and the other experimental groups (P<.05). CONCLUSION: This study
      demonstrates that the highest bond strength between a ceramic and titanium
      substructure can be achieved after airborne-particle abrasion at an angle close
      to 45 degrees with 110-MUm Al2O3 particles under 0.4 MPa of pressure.

PMID- 25749079
TI  - Laser and plasma dental soldering techniques applied to Ti-6Al-4V alloy: ultimate
      tensile strength and finite element analysis.
AB  - STATEMENT OF PROBLEM: The literature provides limited information regarding the
      performance of Ti-6Al-4V laser and plasma joints welded in prefabricated bars in
      dental applications. PURPOSE: The purpose of this study was to evaluate the
      mechanical strength of different diameters of Ti-6Al-4V alloy welded with laser
      and plasma techniques. MATERIAL AND METHODS: Forty-five dumbbell-shaped rods were
      created from Ti-6Al-4V and divided into 9 groups (n=5): a control group with 3-mm
      and intact bars; groups PL2.5, PL3, PL4, and PL5 (specimens with 2.5-, 3-, 4-,
      and 5-mm diameters welded with plasma); and groups L2.5, L3, L4, and L5
      (specimens with 2.5-, 3-, 4-, and 5-mm diameters welded with laser). The
      specimens were tested for ultimate tensile strength (UTS), and elongation
      percentages (EP) were obtained. Fractured specimens were analyzed by
      stereomicroscopy, and welded area percentages (WAP) were calculated. Images were
      made with scanning electron microscopy. In the initial analysis, the data were
      analyzed with a 2-way ANOVA (2*4) and the Tukey Honestly Significant Difference
      (HSD) test. In the second analysis, the UTS and EP data were analyzed with 1-way
      ANOVA, and the Dunnett test was used to compare the 4 experimental groups with
      the control group (alpha=.05). The Pearson and Spearman correlation coefficient
      tests were applied to correlate the study factors. Finite element models were
      developed in a workbench environment with boundary conditions simulating those of
      a tensile test. RESULTS: The 2-way ANOVA showed that the factors welding type and
      diameter were significant for the UTS and WAP values. However, the interaction
      between them was not significant. The 1-way ANOVA showed statistically
      significant differences among the groups for UTS, WAP, and EP values. The Dunnett
      test showed that all the tested groups had lower UTS and EP values than the
      control group. The 2.5- and 3-mm diameter groups showed higher values for UTS and
      WAP than the other test groups. A positive correlation was found between welded
      area percentage and UTS and a negative correlation between these parameters and
      the diameters of the specimens. No statistically significant difference was found
      between the weld techniques. CONCLUSIONS: Under the experimental conditions
      described, diameters of 2.5 and 3 mm resulted in higher UTS and WAP for both
      laser and plasma welding and appear to be the best option for joining
      prefabricated rods in this kind of union.

PMID- 25749080
TI  - Prosthetic rehabilitation of an extensive midfacial and palatal postsurgical
      defect with an implant-supported cross arch framework: a clinical report.
AB  - When aggressive cancer is surgically treated, the extent of the lesion dictates
      the amount of tissue excised. The removal of extensive amounts of tissue,
      including crucial landmarks, complicates prosthesis design. This clinical report
      details the rehabilitation of a patient who had a total maxillectomy coupled with
      extensive surgical removal of the midface. With the aid of computer-generated
      implant placement, a large computer-aided design and computer-aided manufacturing
      milled titanium framework, a Hader bar, and magnetic keepers, a successful
      implant retained definitive obturator and facial prosthesis were fabricated that
      satisfied both esthetic and functional needs.

PMID- 25749081
TI  - Effect of the coefficient of friction and tightening speed on the preload induced
      at the dental implant complex with the finite element method.
AB  - STATEMENT OF PROBLEM: To prevent screw loosening, a clear understanding of the
      factors influencing secure preload is necessary. PURPOSE: The purpose of this
      study was to investigate the effect of coefficient of friction and tightening
      speed on screw tightening based on energy distribution method with exact
      geometric modeling and finite element analysis. MATERIAL AND METHODS: To simulate
      the proper boundary conditions of the screw tightening process, the supporting
      bone of an implant was considered. The exact geometry of the implant complex,
      including the Straumann dental implant, direct crown attachment, and abutment
      screw were modeled with Solidworks software. Abutment screw/implant and
      implant/bone interfaces were designed as spiral thread helixes. The screw
      tightening process was simulated with Abaqus software, and to achieve the target
      torque, an angular displacement was applied to the abutment screw head at
      different coefficients of friction and tightening speeds. The values of torque,
      preload, energy distribution, elastic energy, and efficiency were obtained at the
      target torque of 35 Ncm. Additionally, the torque distribution ratio and preload
      simulated values were compared to theoretically predicted values. RESULTS: Upon
      reducing the coefficient of friction and enhancing the tightening speed, the
      angle of turn increased at the target torque. As the angle of turn increased, the
      elastic energy and preload also increased. Additionally, by increasing the
      coefficient of friction, the frictional dissipation energy increased but the
      efficiency decreased, whereas the increase in tightening speed insignificantly
      affected efficiency. CONCLUSION: The results of this study indicate that the
      coefficient of friction is the most influential factor on efficiency. Increasing
      the tightening speed lowered the response rate to the frictional resistance, thus
      diminishing the coefficient of friction and slightly increasing the preload.
      Increasing the tightening speed has the same result as reducing the coefficient
      of friction.

PMID- 25749082
TI  - Management of pain and sublingual hematoma caused by suture irritation after
      implant surgery: a clinical report.
AB  - Hematoma in the sublingual region is an adverse consequence of implant surgery in
      the mandibular posterior region. Improved knowledge and understanding of the
      anatomy as well as the use of advanced radiographic imaging have all contributed
      to minimizing adverse surgical complications in this region. Delayed sublingual
      hematoma caused by suture irritation after implant surgery has not previously
      been reported. This article describes the management of a patient with a delayed
      sublingual hematoma after implant surgery in the posterior mandible had been
      performed. No evidence of encroachment of the vascular structures was noted at
      the time of implant surgery. However, at a 48-hour follow-up, the patient
      presented with severe pain and irritation of the sublingual mucosa, along with
      extravasation and a collection of blood in the sublingual region. Based on the
      patient's symptoms and clinical signs, the source of the problem was determined
      to be the stiff tags of polypropylene suture, which had been used to attain
      primary closure of the surgical flaps. The situation was conservatively and
      successfully managed by the use of a custom soft tissue guard to protect the
      patient's sublingual mucosa and the tongue from the stiff suture tags. Various
      suture materials and measures for preventing and managing similar situations are
      discussed in this article.

PMID- 25749083
TI  - Effects of different polishing protocols on the surface roughness of Y-TZP
      surfaces used for custom-made implant abutments: a controlled morphologic SEM and
      profilometric pilot study.
AB  - STATEMENT OF PROBLEM: Limited information is available on how to treat the
      surface of computer-aided design/computer-aided manufacturing (CAD/CAM)-derived
      implant abutments made of yttria tetragonal zirconia polycrystal (Y-TZP).
      PURPOSE: The purpose of this study was to assess and compare 4 different
      standardized polishing protocols of dental zirconia with a standard handpiece and
      abrasives and to identify a standardized protocol to obtain a surface roughness
      of Ra=0.2 MUm on dental Y-TZP. MATERIAL AND METHODS: Forty specimens of Y-TZP
      were produced and finished with 4 different polishing protocols with standard
      dental abrasives. Protocol Co used a coarse rubber abrasive, protocol Me used the
      rubber abrasive of protocol Co plus a medium rubber abrasive, protocol Fi used
      the polishing sequences of protocol Me plus a fine rubber abrasive, and protocol
      UF used protocol Me plus ultrafine high-gloss polishing. Ten machined titanium
      disks served as control (C). Roughness measurement and scanning electron
      microscopy was performed for each specimen and tested for differences with ANOVA
      with Bonferroni correction and the Student t test (alpha=.05). RESULTS: In the
      zirconia groups, Co (Ra 0.29 +/-0.38 MUm) showed significantly higher Ra values
      than Me (Ra 0.22 +/-0.38 MUm; P=.003), Fi (Ra 0.17 +/-0.37 MUm; P<.001), and UF
      (Ra 0.07 +/-0.06 MUm; P<.001). UF showed the significantly lowest Ra values of
      all zirconia groups (Co and Me: P<.001, Fi: P=.002). Differences between Me and
      Fi were not significant (P=.116). Comparison of the 4 zirconia surfaces to the
      control group (C; Ra=0.17 +/-0.03) revealed significant differences for Co
      (P<.001) and UF (P=.006) but not Me (P=1.000) and Fi (P=.055). In comparison with
      the literature-based optimal roughness of Ra=0.2 MUm, significant differences
      were found for Co, Fi, and UF (P<.05), but not for Me (P=.117). However, the
      machined titanium surface (C) also showed significantly smoother Ra values than
      0.2 MUm (P<.05, Student t test). CONCLUSIONS: A roughness of Ra=0.2 MUm on
      zirconia can be achieved by following protocol Me, whereas a roughness comparable
      to machined titanium is present after protocol Fi.

PMID- 25749084
TI  - Stress on implant-supported fixed prostheses with different numbers of abutments
      after the application of acrylic resin.
AB  - STATEMENT OF PROBLEM: Clinical procedures and laboratory processing techniques
      inevitably induce stress in the implant/abutment/prosthesis system and may have
      negative effects when different numbers of implants are used. PURPOSE: The
      purpose of the study was to evaluate the tension on the abutments of implant
      supported fixed prostheses and to determine the effect of the application of an
      esthetic veneer (acrylic resin) and the number of abutments (5 or 4). MATERIAL
      AND METHODS: Four palladium-silver alloy cast bars were fabricated to simulate
      implant-supported fixed complete prostheses. Strain gauges were fixed on the
      abutments to measure the tension before and after the application of the esthetic
      veneer. The values of tension were measured in models with 5 or 4 abutments. Data
      were analyzed with a repeated measures ANOVA. RESULTS: No statistically
      significant differences were found for the main factors (esthetic veneer, P=.22;
      number of abutments, P=.14) despite the large effect size. CONCLUSIONS: The
      results of this study suggest that the tension in the abutments of an implant
      supported fixed prosthesis is not affected by the application of acrylic resin
      veneering or by reducing the number of abutments.

PMID- 25749085
TI  - Denture adhesives: a systematic review.
AB  - STATEMENT OF PROBLEM: Denture adhesives have been the objective of scientific
      research for over half a century. Although they are used by denture wearers
      worldwide, investigations of their effectiveness and biocompatibility have led to
      controversial conclusions. PURPOSE: The purpose of this study was to review the
      literature data with regard to the effectiveness and biocompatibility of denture
      adhesives as well as the attitudes of both patients and dental professionals
      toward these materials. MATERIAL AND METHODS: An electronic search of English
      peer-reviewed dental literature in the Medline database was conducted to evaluate
      the effectiveness and biocompatibility of denture adhesives. There was no
      limitation in publication year, so the search included all the available
      scientific evidence included in that particular database until March 2014.
      Specific inclusion criteria were used for the selection of the appropriate
      articles. A manual search of the citations of the obtained articles followed to
      extend the electronic search. RESULTS: A full text review was carried out for
      only 32 articles. Of the 32 articles, 21 examined the efficacy of denture
      adhesives in terms of retention and stability and masticatory performance, 6
      evaluated the issue of the biocompatibility of denture adhesives, and 5 presented
      the attitudes of either professionals or patients toward these materials.
      CONCLUSIONS: The majority of clinical studies supported the fact that denture
      adhesives enhance the retention, stability, and masticatory performance of a
      removable prosthesis. In terms of biocompatibility, long-term in vivo studies to
      investigate potential harmful effects were lacking. Patients are satisfied with
      denture adhesives that meet their needs.

PMID- 25749086
TI  - A radiographic measurement technique for crest bone changes related to dental
      implants.

PMID- 25749087
TI  - A technique for facilitating pattern fabrication and clinical evaluation in
      partial auricular defects.

PMID- 25749088
TI  - Penetration depth of monomer systems into acrylic resin denture teeth used as
      pontics.
AB  - STATEMENT OF PROBLEM: The ways of softening and dissolving the surface of acrylic
      resin denture teeth need to be specified to obtain more durable prosthetic
      treatments that include resin denture teeth. PURPOSE: The purpose of this study
      was to analyze the penetration depth of 4 monomer systems applied during
      different exposure times on the acrylic resin denture teeth used as pontics of
      directly fabricated fiber-reinforced composite fixed dental prostheses. The
      penetration depth contributes to the adhesion of the tooth to the adhesive resin.
      MATERIAL AND METHODS: Ninety-six specimens were divided into 3 groups according
      to the acrylic resin denture tooth used: Artic 8 (Heraeus Kultzer), experimental
      tooth (GC), and Vitapan (Vita). Each group was divided into 4 subgroups according
      to the monomer system used: methylmethacrylate (99%), composite primer, a
      flowable composite resin, and a photopolymerizing dimethacrylate resin. The 4
      monomer systems were labeled with rhodamine B to determine their penetration
      depth into the acrylic resin denture teeth. After exposure times of 1, 5, 15, and
      60 minutes, the monomers were photopolymerized for 5 minutes, with the exception
      of methylmethacrylate. The specimens were cut orthogonally from gingival to
      occlusal in 4 slices (n=8/subgroup). The penetration depths of monomers were
      measured by a confocal scanning type microscope. Differences in the penetration
      depths were evaluated with ANOVA. RESULTS: ANOVA (R(2)=.699) revealed significant
      differences in the penetration depths according to the exposure times (P<.001),
      monomers (P<.001), brands used (P=.047), and their mutual interaction (P<.001).
      CONCLUSIONS: The ability of monomers to penetrate the surface of acrylic resin
      denture teeth was influenced by the monomer systems, which might improve the bond
      between the pontics and the fiber-reinforced composite frameworks of fixed dental
      prostheses.

PMID- 25749089
TI  - Effect of implant angulation and impression technique on impressions of
      NobelActive implants.
AB  - STATEMENT OF PROBLEM: How the configuration of the NobelActive internal conical
      connection affects implant impressions is uncertain. PURPOSE: The purpose of this
      study was to measure the effect in vitro of closed and open tray impression
      techniques for NobelActive implants placed at various angulations. MATERIAL AND
      METHODS: Six NobelActive implants were placed in a master maxillary cast as
      follows: 0 degrees of angulation to a line drawn perpendicular to the occlusal
      plane in the first molar area, 15 degrees of angulation to a line drawn
      perpendicular to the occlusal plane in the first premolar area, and 30 degrees of
      angulation to a line drawn perpendicular to the occlusal plane in the lateral
      incisor area. Twelve open tray and 12 closed tray impressions were made.
      Occlusal, lateral, and frontal view photographs of the resulting casts were used
      to measure the linear and angular displacement of implant analogs. Statistical
      analysis was performed with a factorial analysis of variance (ANOVA), followed by
      the Tukey HSD test (alpha=.05). RESULTS: No significant difference was found in
      the impressions made of NobelActive implants with the open or closed tray
      technique (linear displacement: F=0.93, P=.34; angular displacement: F=2.09,
      P=.15). In addition, implant angulation (0, 15, or 30 degrees) had no effect on
      the linear or angular displacement of impressions (linear displacement: F=2.72,
      P=.07; angular displacement: F=0.86, P=.43). Finally, no significant interaction
      was found between impression technique and implant angulation on NobelActive
      implants (F=0.25, P=.77; F=1.60, P=.20). CONCLUSIONS: Within the limitations of
      this study, impression technique (open vs closed tray) and implant angulation (0,
      15, and 30 degrees) had no significant effect on in vitro impressions of
      NobelActive implants.

PMID- 25749090
TI  - Effect of airborne-particle abrasion of presintered zirconia on surface roughness
      and bacterial adhesion.
AB  - STATEMENT OF PROBLEM: Factors associated with implant periodontal disease of
      zirconia restorations such as surface roughness remain largely unknown. PURPOSE:
      The purpose of this study was to investigate how airborne-particle abrasion
      before sintering affects roughness and bacterial adhesion on the surface of
      zirconia. MATERIAL AND METHODS: Thirty presintered zirconia specimens were
      divided into 6 groups of 5 after being polished with silicon carbide paper (1200
      grit). A different surface treatment was applied to each group (no treatment
      [group Ct] and 120-MUm alumina abrasion for 5, 8, 10, 12, and 15 seconds [A5s,
      A8s, A10s, A12s, and A15s]), and the specimens were then densely sintered. The
      mean centric linear roughness (Ra) was measured, and the 3D measurement of
      surface roughness (3D roughness) was determined. The number of colony forming
      units (CFUs) of Streptococcus mutans adhering to the surface was also examined.
      One-way ANOVA was used for data analysis (alpha=.05). RESULTS: Airborne-particle
      abrasion before sintering significantly increased surface roughness. Group A8s,
      A10s, A12s, and A15s showed statistically significant higher CFU/mL than did
      group A5s (P<.05). No difference was found in CFU/mL between group Ct and A5s
      (P=.230). CONCLUSIONS: Airborne-particle abrasion before sintering is a useful
      method of increasing the surface roughness of zirconia. Ra < 0.58 MUm is
      necessary to inhibit the adherence of S. mutans to zirconia.

PMID- 25749091
TI  - Effect of joint design and welding type on the flexural strength and weld
      penetration of Ti-6Al-4V alloy bars.
AB  - STATEMENT OF PROBLEM: Framework longevity is a key factor for the success of
      complete-arch prostheses and commonly depends on the welding methods. However, no
      consensus has been reached on the joint design and welding type for improving
      framework resistance. PURPOSE: The purpose of this study was to assess the effect
      of different joint designs and welding methods with tungsten inert gas (TIG) or
      laser to join titanium alloy bars (Ti-6Al-4V). MATERIAL AND METHODS: Seventy
      titanium alloy bar specimens were prepared (3.18 mm in diameter * 40.0 mm in
      length) and divided into 7 groups (n=10): the C-control group consisting of
      intact specimens without joints and the remaining 6 groups consisting of
      specimens sectioned perpendicular to the long-axis and rejoined using an I-, X30
      , or X45-shaped joint design with TIG welding (TI, TX30, and TX45) or laser
      welding (LI, LX30, and LX45). The specimens were tested with 3-point bending. The
      fracture surfaces were first evaluated with stereomicroscopy to measure the weld
      penetration area and then analyzed with scanning electron microscopy (SEM). The
      data were statistically analyzed with 2-way ANOVA and the Tukey post hoc test, 1
      way ANOVA and the Dunnett test, and the Pearson correlation test (alpha=.05).
      RESULTS: Specimens from the X30 and X45 groups showed higher flexural strength
      (P<.05) and welded area (P<.05) than specimens from the I groups, regardless of
      the welding type. TIG welded groups showed significantly higher flexural strength
      than the laser groups (P<.05), regardless of the joint design. TIG welding also
      resulted in higher welded areas than laser welding for the I-shaped specimens. No
      significant differences were found for the weld penetration area in the X45
      group, either for laser or TIG welding. SEM analysis showed more pores at the
      fracture surfaces of the laser specimens. Fracture surfaces indicative of regions
      of increased ductility were detected for the TIG specimens. CONCLUSIONS: TIG
      welding resulted in higher flexural strength for the joined titanium specimens
      than laser welding. For both welding methods, X30- and X45-shaped joint designs
      resulted in higher flexural strength and welding penetration than the I-shaped
      joint design.

PMID- 25749092
TI  - Dynamic nature of abutment screw retightening: finite element study of the effect
      of retightening on the settling effect.
AB  - STATEMENT OF PROBLEM: A fundamental problem in fully understanding the dynamic
      nature of screw loosening is lack of recognition of the entire process of screw
      tightening and retightening. PURPOSE: The purpose of this study was to explain
      the dynamic nature of abutment screw retightening by using finite element methods
      to investigate the effect of the coefficient of friction and retightening on the
      settling effect. MATERIAL AND METHODS: Precise computer models were designed of a
      Straumann dental implant, a directly attached crown, an abutment screw, and the
      bone surrounding the implant. All threaded interfaces were designed with a spiral
      thread helix with a specific coefficient of static and kinetic friction, and the
      surfaces were characterized as fine, regular, and rough. Abaqus software was used
      for dynamic simulation, which involved applying rotational displacement to the
      abutment screw and torque controlling during the steps of tightening, relaxation,
      retightening, and second relaxation and at different coefficients of friction.
      The obtained torque and preload values were compared to the predicted values.
      RESULTS: When surfaces changed from fine to rough, the remaining torque and
      preload decreased, and the settling effect increased. Upon retightening, the
      remaining torque and preload increased, and the settling effect also decreased.
      CONCLUSIONS: The reduction of the coefficient of friction contributes to
      increases in the preload and decreases in the settling effect. Retightening
      reduced the settling effect and had an insignificant effect on the preload. At
      high coefficients of friction, the retightening effect was intensified.

PMID- 25749093
TI  - Translucency of esthetic dental restorative CAD/CAM materials and composite
      resins with respect to thickness and surface roughness.
AB  - STATEMENT OF PROBLEM: Little information is available about the translucency of
      monolithic CAD/CAM materials. PURPOSE: The purpose of this study was to evaluate
      the translucency of restorative CAD/CAM materials and direct composite resins
      with respect to thickness and surface roughness. MATERIALS AND METHODS: In total,
      240 disk-shaped specimens (12*14*1 mm and 12*14*2 mm) of 3 different CAD/CAM
      glass ceramics (CELTRA Duo, IPS e.max CAD, IPS Empress CAD), a fine-structure
      feldspathic ceramic (VITA Mark II), a hybrid ceramic (VITA Enamic), a resin
      nanoceramic composite resin (LAVA Ultimate), an experimental (CAD/CAM nanohybrid
      composite resin), 2 interim materials (Telio CAD; VITA CAD-Temp), and 3 direct
      composite resins (Tetric EvoCeram; Filtek Supreme XTE; Tetric EvoCeram Bulk Fill)
      were fabricated (n=10). After 3 different surface pretreatments (polished, rough
      SiC P1200, or SiC P500), absolute translucency and surface roughness were
      measured using spectrophotometry and tactile profilometry. The influence of
      material type, thickness, and roughness on absolute translucency was analyzed
      using a multivariate analysis, 1-way ANOVA, and the Tukey HSD post hoc test
      (P<.05). Pearson correlations and statistical hypothesis tests were used to
      assess the results (P<.05). RESULTS: The effect of all tested parameters was
      significant among the materials (P<.05). The greatest influence on the measured
      translucency was thickness (partial eta squared etaP2=.988), closely followed by
      material (.982), and the pretreatment method (.835). The surface roughness was
      strongly influenced by the pretreatment method (.975) and type of material
      (.941). CONCLUSION: Thickness and surface roughness are major factors affecting
      the absolute translucency of adhesively luted restorations.

PMID- 25749096
TI  - An international comparison of the association among literacy, education, and
      health across the United States, Canada, Switzerland, Italy, Norway, and Bermuda:
      implications for health disparities.
AB  - The relationship between education and health is well-established, but
      theoretical pathways are not fully understood. Economic resources, stress, and
      health behaviors partially explain how education influences health, but further
      study is needed. Previous studies show that health literacy mediates the
      education-health relationship, as do general literacy skills. However, little is
      known whether such mediation effects are consistent across different societies.
      This study analyzed data from the International Assessment of Adult Literacy and
      Life Skills Survey conducted in Canada, the United States, Italy, Norway,
      Switzerland, and Bermuda to investigate the mediation effects of literacy on the
      education-health relationship and the degree of such mediation in different
      cultural contexts. Results showed that literacy skills mediated the effect of
      education on health in all study locations, but the degree of mediation varied.
      This mediation effect was particularly strong in Bermuda. This study also found
      that different types of literacy skills are more or less important in each study
      location. For example, numeracy skills in the United States and prose (reading)
      literacy skills in Italy were stronger predictors of health than were other
      literacy skills. These findings suggest a new direction for addressing health
      disparities: focusing on relevant types of literacy skills. 

PMID- 25749095
TI  - Retinoic acid-induced IgG production in TLR-activated human primary B cells
      involves ULK1-mediated autophagy.
AB  - In the present study we have established a vital role of autophagy in retinoic
      acid (RA)-induced differentiation of toll-like receptor (TLR)-stimulated human B
      cells into Ig-secreting cells. Thus, RA enhanced autophagy in TLR9- and CD180
      stimulated peripheral blood B cells, as revealed by increased levels of the
      autophagosomal marker LC3B-II, enhanced colocalization between LC3B and the
      lysosomal marker Lyso-ID, by a larger percentage of cells with more than 5
      characteristic LC3B puncta, and by the concomitant reduction in the level of
      SQSTM1/p62. Furthermore, RA induced expression of the autophagy-inducing protein
      ULK1 at the transcriptional level, in a process that required the retinoic acid
      receptor RAR. By inhibiting autophagy with specific inhibitors or by knocking
      down ULK1 by siRNA, the RA-stimulated IgG production in TLR9- and CD180-mediated
      cells was markedly reduced. We propose that the identified prominent role of
      autophagy in RA-mediated IgG-production in normal human B cells provides a novel
      mechanism whereby vitamin A exerts its important functions in the immune system. 

PMID- 25749094
TI  - Cellular connections, microenvironment and brain angiogenesis in diabetes: Lost
      communication signals in the post-stroke period.
AB  - Diabetes not only increases the risk but also worsens the motor and cognitive
      recovery after stroke, which is the leading cause of disability worldwide. Repair
      after stroke requires coordinated communication among various cell types in the
      central nervous system as well as circulating cells. Vascular restoration is
      critical for the enhancement of neurogenesis and neuroplasticity. Given that
      vascular disease is a major component of all complications associated with
      diabetes including stroke, this review will focus on cellular communications that
      are important for vascular restoration in the context of diabetes. This article
      is part of a Special Issue entitled SI: Cell Interactions In Stroke. 

PMID- 25749097
TI  - Prenatal stress enhances excitatory synaptic transmission and impairs long-term
      potentiation in the frontal cortex of adult offspring rats.
AB  - The effects of prenatal stress procedure were investigated in 3 months old male
      rats. Prenatally stressed rats showed depressive-like behavior in the forced swim
      test, including increased immobility, decreased mobility and decreased climbing.
      In ex vivo frontal cortex slices originating from prenatally stressed animals,
      the amplitude of extracellular field potentials (FPs) recorded in cortical layer
      II/III was larger, and the mean amplitude ratio of pharmacologically-isolated
      NMDA to the AMPA/kainate component of the field potential--smaller than in
      control preparations. Prenatal stress also resulted in a reduced magnitude of
      long-term potentiation (LTP). These effects were accompanied by an increase in
      the mean frequency, but not the mean amplitude, of spontaneous excitatory
      postsynaptic currents (sEPSCs) in layer II/III pyramidal neurons. These data
      demonstrate that stress during pregnancy may lead not only to behavioral
      disturbances, but also impairs the glutamatergic transmission and long-term
      synaptic plasticity in the frontal cortex of the adult offspring.

PMID- 25749098
TI  - Basal Hippocampal Activity and Its Functional Connectivity Predicts Cocaine
      Relapse.
AB  - BACKGROUND: Cocaine-induced neuroplastic changes may result in a heightened
      propensity for relapse. Using regional cerebral blood flow (rCBF) as a marker of
      basal neuronal activity, this study assessed alterations in rCBF and related
      resting state functional connectivity (rsFC) to prospectively predict relapse in
      patients following treatment for cocaine use disorder (CUD). METHODS:
      Pseudocontinuous arterial spin labeling functional magnetic resonance imaging and
      resting blood oxygen level-dependent functional magnetic resonance imaging data
      were acquired in the same scan session in abstinent participants with CUD before
      residential treatment discharge and in 20 healthy matched control subjects.
      Substance use was assessed twice weekly following discharge. Relapsed
      participants were defined as those who used stimulants within 30 days following
      treatment discharge (n = 22); early remission participants (n = 18) did not.
      RESULTS: Voxel-wise, whole-brain analysis revealed enhanced rCBF only in the left
      posterior hippocampus (pHp) in the relapsed group compared with the early
      remission and control groups. Using this pHp as a seed, increased rsFC strength
      with the posterior cingulate cortex (PCC)/precuneus was seen in the relapsed
      versus early remission subgroups. Together, both increased pHp rCBF and
      strengthened pHp-PCC rsFC predicted relapse with 75% accuracy at 30, 60, and 90
      days following treatment. CONCLUSIONS: In CUD participants at risk of early
      relapse, increased pHp basal activity and pHp-PCC circuit strength may reflect
      the propensity for heightened reactivity to cocaine cues and persistent cocaine
      related ruminations. Mechanisms to mute hyperactivated brain regions and delink
      dysregulated neural circuits may prove useful to prevent relapse in patients with
      CUD.

PMID- 25749100
TI  - Phthalates and neurotoxic effects on hippocampal network plasticity.
AB  - Phthalates are synthetically derived chemicals used as plasticizers in a variety
      of common household products. They are not chemically bound to plastic polymers
      and over time, easily migrate out of these products and into the environment.
      Experimental investigations evaluating the biological impact of phthalate
      exposure on developing organisms are critical given that estimates of phthalate
      exposure are considerably higher in infants and children compared to adults.
      Extensive growth and re-organization of neurocircuitry occurs during development
      leaving the brain highly susceptible to environmental insults. This review
      summarizes the effects of phthalate exposure on brain structure and function with
      particular emphasis on developmental aspects of hippocampal structural and
      functional plasticity. In general, it appears that widespread disruptions in
      hippocampal functional and structural plasticity occur following developmental
      (pre-, peri- and post-natal) exposure to phthalates. Whether these changes occur
      as a direct neurotoxic effect of phthalates or an indirect effect through
      disruption of endogenous endocrine functions is not fully understood.
      Comprehensive investigations that simultaneously assess the neurodevelopmental,
      neurotoxic, neuroendocrine and behavioral correlates of phthalate exposure are
      needed to provide an opportunity to thoroughly evaluate the neurotoxic potential
      of phthalates throughout the lifespan. 

PMID- 25749099
TI  - Alterations of Mitochondrial DNA Copy Number and Telomere Length With Early
      Adversity and Psychopathology.
AB  - BACKGROUND: Telomere shortening and alterations of mitochondrial biogenesis are
      involved in cellular aging. Childhood adversity is associated with telomere
      shortening, and several investigations have shown short telomeres in psychiatric
      disorders. Recent studies have examined whether mitochondria might be involved in
      neuropsychiatric conditions; findings are limited and no prior work has examined
      this in relation to stress exposure. METHODS: Two-hundred ninety healthy adults
      provided information on childhood parental loss and maltreatment and completed
      diagnostic interviews. Participants were categorized into four groups based upon
      the presence or absence of childhood adversity and the presence or absence of
      lifetime psychopathology (depressive, anxiety, and substance use disorders).
      Telomere length and mitochondrial DNA (mtDNA) copy number were measured from
      leukocyte DNA by quantitative polymerase chain reaction. RESULTS: Childhood
      adversity and lifetime psychopathology were each associated with shorter
      telomeres (p < .01) and higher mtDNA copy numbers (p < .001). Significantly
      higher mtDNA copy numbers and shorter telomeres were seen in individuals with
      major depression, depressive disorders, and anxiety disorders, as well as those
      with parental loss and childhood maltreatment. A history of substance disorders
      was also associated with significantly higher mtDNA copy numbers. CONCLUSIONS:
      This study provides the first evidence of an alteration of mitochondrial
      biogenesis with early life stress and with anxiety and substance use disorders.
      We replicate prior work on telomere length and psychopathology and show that this
      effect is not secondary to medication use or comorbid medical illness. Finally,
      we show that early life stress and psychopathology are each associated with these
      markers of cellular aging.

PMID- 25749101
TI  - Towards a comprehensive understanding of brain machinery by correlative
      microscopy.

PMID- 25749102
TI  - Altered core and skin temperature responses to endurance exercise in heart
      failure patients and healthy controls.
AB  - BACKGROUND: Exercise training represents a central aspect of rehabilitation of
      heart failure patients. Previous work on passive heating suggests impaired
      thermoregulatory responses in heart failure patients. However, no previous study
      directly examined thermoregulatory responses to an exercise bout, that is, active
      heating, as typically applied in rehabilitation settings in heart failure.
      DESIGN: Cross-sectional observational study to compare changes in core body
      temperature (Tcore) and skin temperature (Tskin) during exercise between heart
      failure patients and controls. METHODS: Fourteen heart failure subjects (65 +/- 7
      years, 13:1 male:female) and 14 healthy controls (61 +/- 5 years, 12:2
      male:female) were included. Tcore (telemetric temperature pill) and Tskin (skin
      thermistors) were measured continuously during a 45-min cycle exercise at
      comparable relative exercise intensity. RESULTS: Tcore increased to a similar
      extent in both groups (controls 1.1 +/- 0.4C, heart failure patients 0.9 +/-
      0.3C, 'time*group': p = 0.15). Tskin decreased during the initial phase of
      exercise in both groups, followed by an increase in Tskin in controls (1.2 +/-
      1.0C), whilst Tskin remained low in HF patients (-0.3 +/- 1.4C) ('time*group': p
      < 0.001). Furthermore, we found that a given change in Tcore was associated with
      a smaller increase in Tskin in heart failure patients compared with controls.
      When comparing heart failure patients and controls who performed exercise at
      similar absolute workload, between-group differences disappeared (p-values >
      0.05). CONCLUSION: Heart failure patients and controls show comparable exercise
      induced increase in Tcore, whilst heart failure patients demonstrate altered
      Tskin responses to exercise and attenuated elevation in Tskin per increase in
      Tcore. These impaired thermoregulatory responses to exercise are, at least
      partly, explained by the lower absolute workload and lower physical fitness level
      in heart failure patients.

PMID- 25749104
TI  - Pregnane X receptor knockout mice display aging-dependent wearing of articular
      cartilage.
AB  - Steroid and xenobiotic receptor (SXR) and its murine ortholog, pregnane X
      receptor (PXR), are nuclear receptors that are expressed at high levels in the
      liver and the intestine where they function as xenobiotic sensors that induce
      expression of genes involved in detoxification and drug excretion. Recent
      evidence showed that SXR and PXR are also expressed in bone tissue where they
      mediate bone metabolism. Here we report that systemic deletion of PXR results in
      aging-dependent wearing of articular cartilage of knee joints.
      Histomorphometrical analysis showed remarkable reduction of width and an enlarged
      gap between femoral and tibial articular cartilage in PXR knockout mice. We
      hypothesized that genes induced by SXR in chondrocytes have a protective effect
      on articular cartilage and identified Fam20a (family with sequence similarity
      20a) as an SXR-dependent gene induced by the known SXR ligands, rifampicin and
      vitamin K2. Lastly, we demonstrated the biological significance of Fam20a
      expression in chondrocytes by evaluating osteoarthritis-related gene expression
      of primary articular chondrocytes. Consistent with epidemiological findings, our
      results indicate that SXR/PXR protects against aging-dependent wearing of
      articular cartilage and that ligands for SXR/PXR have potential role in
      preventing osteoarthritis caused by aging. 

PMID- 25749105
TI  - Extremophilic polysaccharide nanoparticles for cancer nanotherapy and evaluation
      of antioxidant properties.
AB  - Polysaccharides that show finest bioactivities and physicochemical properties are
      always promising for bionanoscience applications. Mauran is such a macromolecule
      extracted from halophilic bacterium, Halomonas maura for biotechnology and
      nanoscience applications. Antioxidant properties of MR/CH nanoparticles were
      studied using biochemical assays to prove the versatility of these test
      nanoparticles for biomedical applications. Here, we demonstrate the prospects of
      extremophilic polysaccharide, mauran based nanoparticles for scavenging reactive
      oxygen species in both in vitro and ex vivo conditions. 5-fluorouracil loaded
      MR/CH nanoparticles were tested for anticancer proliferation and compared their
      therapeutic efficiency using breast adenocarcinoma and glioma cells.
      Fluorescently labeled nanoparticles were employed to show the cellular uptake of
      these nanocarriers using confocal microscopic imaging and flow cytometry. 

PMID- 25749103
TI  - Regulation of Oxidative Stress in Pulmonary Artery Endothelium. Modulation of
      Extracellular Superoxide Dismutase and NOX4 Expression Using Histone Deacetylase
      Class I Inhibitors.
AB  - An imbalance between oxidants and antioxidants is considered a major factor in
      the development of pulmonary vascular diseases. Oxidative stress seen in
      pulmonary vascular cells is regulated by increased expression of prooxidant
      enzymes (e.g., nicotinamide adenine dinucleotide phosphate reduced oxidases)
      and/or decreased production of antioxidants and antioxidant enzymes (e.g.,
      superoxide dismutases). We and others have shown that expression of antioxidant
      genes in pulmonary artery cells is regulated by epigenetic mechanisms. In this
      study, we investigate the regulation of oxidative stress in pulmonary artery
      cells using inhibitors of histone deacetylases (HDACs). Human pulmonary artery
      endothelial cells (HPAECs) and human pulmonary artery smooth muscle cells were
      exposed to an array of HDAC inhibitors followed by analysis of anti- and
      prooxidant gene expression using quantitative RT-PCR and quantitative RT-PCR
      array. We found that exposure of HPAECs to scriptaid, N-[4
      [(hydroxyamino)carbonyl]phenyl]-alpha-(1-methylethyl)-benzeneacetamide, and
      trichostatin A for 24 hours induced expression of extracellular superoxide
      dismutase (EC-SOD) up to 10-fold, whereas expression of the prooxidant gene NADPH
      oxidase 4 was decreased by more than 95%. We also found that this differential
      regulation of anti- and prooxidant gene expression resulted in significant
      attenuation in the cellular levels of reactive oxygen species. Induction of EC
      SOD expression was attenuated by the Janus kinase 2 protein kinase inhibitor
      AG490 and by silencing Janus kinase 2 expression. Augmentation of EC-SOD
      expression using scriptaid was associated with increased histone H3 (Lys27)
      acetylation and H3 (Lys4) trimethylation at the gene promoter. We have determined
      that oxidative stress in pulmonary endothelial cells is regulated by epigenetic
      mechanisms and can be modulated using HDAC inhibitors.

PMID- 25749106
TI  - Intrinsic viscosity and rheological properties of natural and substituted guar
      gums in seawater.
AB  - The intrinsic viscosity and rheological properties of guar gum (GG),
      hydroxypropyl guar (HPG) and carboxymethyl guar (CMG) in seawater and the effects
      of shear rate, concentration, temperature and pH on these properties were
      investigated. An intrinsic viscosity-increasing effect was observed with GG and
      HPG in seawater (SW) compared to deionized water (DW), whereas the intrinsic
      viscosity of CMG in seawater was much lower than that in DW due to a screening
      effect that reduced the repulsion between the polymer chains. Regardless of the
      functional groups, all sample solutions was well characterized by a modified
      Cross model that exhibited the transition from Newtonian to pseudoplastic in the
      low shear rate range at the concentrations of interest to industries, and their
      viscosity increased with the increase in their concentration but decreased with
      the increase in temperature. In contrast to nonionic GG or HPG, anionic CMG had a
      slightly decreased viscosity property in SW, exhibiting polyelectrolyte viscosity
      behavior. The alpha value in the zero-shear rate viscosity vs. concentration
      power-law equation for the samples gave the order of CMG>HPG>GG while the SW
      solution of CMG had the lowest viscous flow activation energy and exhibited a
      strong pH-dependent viscosity by a different shear rate. 

PMID- 25749107
TI  - Cognitive rigidity is mirrored by autonomic inflexibility in daily life
      perseverative cognition.
AB  - Mind wandering (MW) can be persistent and therefore has been included in the
      repetitive thinking conceptualization. In line with a dimensional view of
      psychopathology, we hypothesized the existence of a MW-Perseverative Cognition
      (PC) continuum, where the latter is characterized by a rigid and defensive
      pattern with attentional, behavioral, affective, and autonomic perseverative
      manifestations. Ambulatory heart rate (HR) and variability (HRV) of 42
      participants were recorded for 24h. Approximately every 30 min during waking,
      subjects reported their ongoing thoughts and moods using electronic diaries. MW
      was characterized by less effort to inhibit the thought and less interference
      with ongoing activities, absence of mood worsening, and higher HRV compared to
      PC. Worse sleep quality was predicted by higher levels of trait rumination and
      daily PC. Results suggest that MW and PC represent the functional and
      pathological ends of a continuum, respectively.

PMID- 25749108
TI  - Determination of para-arsanilic acid with improved diazotization reaction using
      differential pulse cathodic stripping voltammetry in aqueous system.
AB  - Para-arsanilic acid (p-ASA) has been widely used in the poultry industry to
      promote growth and prevent dysentery. It is excreted unchanged in the manure and
      released into non-target sites causing organoarsenic pollution risk to the
      environment and living system. Therefore, simple and effective analytical
      strategies are demanded for determining the samples that contain p-ASA. However,
      direct determination of both p-ASA and ortho-arsanilic acid (o-ASA) using
      differential pulse cathodic stripping voltammetry (DPCSV) gives the similar
      voltammograms that directly hamper the analysis used by the DPCSV technique. In
      this study, a method to determine and differentiate p-ASA from o-ASA via
      diazotization and coupling reaction of the amine groups followed by the direct
      DPCSV determination of diazo compounds is presented. The diazotization reaction
      carried out at pH 1.5 and 0 +/- 1 degrees C for 10 min showed two reduction peaks
      in DPCSV at-70 mV and -440 mV vs. Ag/AgCl (KCl 3 M). However, when the
      diazotization reaction was performed at pH 12.5 and 0 +/- 1 degrees C for 40 min,
      a coloured azo compound was produced and the DPCSV showed only one reduction peak
      that appeared at -600 mV vs. Ag/AgCl (3 M of KCl). The results of this study show
      that only p-ASA compound gave a reduction peak, whereas o-ASA compound did not
      give any peak. The detection limit of p-ASA was found to be 4 * 10(-8 )M. As a
      result, the proposed electro-analytical technique might be a good candidate to
      determine and differentiate the p-ASA present in the poultry and environmental
      samples.

PMID- 25749109
TI  - A conceptual framework for Taiwan's hospital clinical performance indicators.

PMID- 25749110
TI  - Evaluation of crown-root angulation of lateral incisors adjacent to palatally
      impacted canines.
AB  - BACKGROUND: The objective of this study is to explore differences in crown-to
      root angulation between lateral incisors adjacent to palatally impacted canines
      (PICs) and lateral incisors adjacent to normally erupted canines (NECs). METHODS:
      Orthodontic records of 100 subjects (51 with PICs and 49 with NECs) were
      reviewed. Crown-to-root angulations of all lateral incisors were measured
      manually on the final panoramic radiographs. Also, three experienced
      orthodontists were asked to visually inspect the morphology of the lateral
      incisors on the panoramic radiographs. A mixed model was used to test the
      difference in crown-to-root angulation of the lateral incisor between the
      experimental and the control groups. The association between the examiners'
      observations and the presence of a canine impaction was assessed by means of a
      chi-square test. All analyses were performed at the 0.05 level of statistical
      significance. RESULTS: A significant (p = 0.009) difference of 2.3 degrees  in
      crown-to-root angulation was found between groups. Also, 66.7% of the lateral
      incisors that were identified as "abnormal" by the panel of orthodontists were
      adjacent to a PIC. A percentage of 65.2 of lateral incisors that were identified
      as "normal" were located adjacent to NECs. CONCLUSIONS: The root of lateral
      incisors adjacent to PICs is angulated more mesially compared to lateral incisors
      adjacent to NECs. In addition, clinicians are somewhat able to predict if a
      canine is palatally impacted by visually observing the crown-to-root angulation
      of the adjacent lateral incisor. Evaluating the crown-to-root angulation of a
      lateral incisor on a panoramic image might facilitate an early diagnosis of
      palatally impacted canines.

PMID- 25749111
TI  - Subcellular Redistribution of Root Aquaporins Induced by Hydrogen Peroxide.
AB  - Aquaporins are water channel proteins that mediate the fine-tuning of cell
      membrane water permeability during development or in response to environmental
      stresses. The present work focuses on the oxidative stress-induced redistribution
      of plasma membrane intrinsic protein (PIP) aquaporins from the plasma membrane
      (PM) to intracellular membranes. This process was investigated in the Arabidopsis
      root. Sucrose density gradient centrifugation showed that exposure of roots to
      0.5 mM H2O2 induces significant depletion in PM fractions of several abundant PIP
      homologs after 15 min. Analyses by single-particle tracking and fluorescence
      correlative spectroscopy showed that, in the PM of epidermal cells, H2O2
      treatment induces an increase in lateral motion and a reduction in the density of
      a fluorescently tagged form of the prototypal AtPIP2;1 isoform, respectively. Co
      expression analyses of AtPIP2;1 with endomembrane markers revealed that H2O2
      triggers AtPIP2;1 accumulation in the late endosomal compartments. Life-time
      analyses established that the high stability of PIPs was maintained under
      oxidative stress conditions, suggesting that H2O2 triggers a mechanism for
      intracellular sequestration of PM aquaporins without further degradation. In
      addition to information on cellular regulation of aquaporins, this study provides
      novel and complementary insights into the dynamic remodeling of plant internal
      membranes during oxidative stress responses. 

PMID- 25749112
TI  - Efficient Virus-Mediated Genome Editing in Plants Using the CRISPR/Cas9 System.

PMID- 25749113
TI  - [Is screening for lung cancer within reach?].

PMID- 25749114
TI  - [Virus in the brain].

PMID- 25749115
TI  - [Continuous heart rehabilitation - how hard can it be?].

PMID- 25749116
TI  - [Fibrin adhesives and cyanoacrylates in surgical specialties].
AB  - Fibrin adhesives and cyanoacrylates are used in surgical specialties due to their
      ability of fixating tissue. The fibrin-based adhesives mimic the blood's own
      coagulation cascade, while the cyanoacrylate-based products function like
      commercially available superglue. The use of adhesives varies from skin
      lacerations to highly complicated surgical procedures, and adhesives provide an
      alternative or combined method of fixation to traditional fixation as suture. We
      present results from various clinical studies to investigate the use of fibrin
      based and cyanoacrylate adhesives. 

PMID- 25749117
TI  - [Flow cytometry: a fast method to detect foetomaternal haemorrhage].
AB  - The passage of foetal blood into maternal circulation is termed a foetomaternal
      haemorrhage (FMH). Most cases are clinically insignificant. However, in some
      cases a large FMH causes serious anaemia in the newborn child. Flow cytometry is
      a precise and fast method to analyse maternal blood for FMH and can be used both
      antenatally and postnatally. The clinician should consider using the analysis in
      cases of unexplained anaemia. We describe a case with severe FMH. 

PMID- 25749118
TI  - [Analgesic management of acute pain in patients receiving methadone or
      buprenorphine].
AB  - In Denmark, approximately 7,600 patients receive maintenance therapy with
      methadone or buprenorphine because of opioid addiction. These patients have an
      increased risk of inadequate pain treatment during hospitalization, among others
      because of tolerance to opioids and poor communication with the staff. The
      present article describes four common misconceptions among health-care providers
      that underlie inadequate pain treatment and provides practical recommendations
      for the analgesic management of acute pain in patients receiving methadone or
      buprenorphine. 

PMID- 25749119
TI  - [Neurogenic oropharyngeal dysphagia is a frequent condition in patients admitted
      to the ICU].
AB  - Neurogenic oropharyngeal dysphagia (NOD) is a frequent condition in neurological
      patients admitted to the ICU, particularly in patients with brainstem lesions.
      The CNS damage itself can predispose to dysphagia, but also the treatment and
      preventive measures may predispose to and exacerbate the condition. Frequent
      pneumonia in a neurological patient is a warning signal that should cause
      screening for dysphagia. Complications are serious and can be fatal. Neurological
      patients should be examined for NOD before decannulation. Treatment is difficult,
      so prevention and multidisciplinary neurological rehabilitation is important. 

PMID- 25749120
TI  - [Sexual side effects after radical prostatectomy are not limited to erectile
      dysfunction].
AB  - Urinary incontinence (UI) during sexual activity, orgasmic dysfunction, and
      altered penile morphology are common sexual side effects after radical
      prostatectomy (RP). However, in spite of research showing that the vast majority
      of patients experience one or more of these problems, they are unknown to most
      clinicians. Daytime UI, non-nerve sparing surgery, and erectile dysfunction can
      help identify patients at risk. Prior to surgery, patients should be informed of
      the above-mentioned side effects. Patients with manifest symptoms after an RP may
      benefit from expert sexual counselling. 

PMID- 25749121
TI  - 6th Drug Hypersensitivity Meeting (DHM 6).

PMID- 25749122
TI  - Current state of anti-PD-L1 and anti-PD-1 agents in cancer therapy.
AB  - Immunotherapy for the treatment of cancer is rapidly evolving from therapies that
      globally and non-specifically simulate the immune system to more targeted
      activation of individual components of the immune system. The net result of this
      targeted approach is decreased toxicity and increased efficacy of immunotherapy.
      More specifically, therapies that inhibit the interaction between programmed
      death ligand 1 (PD-L1), present on the surface of tumor or antigen-presenting
      cells, and programmed death 1 (PD-1), present on the surface of activated
      lymphocytes, are generating much excitement and enthusiasm, even in malignancies
      that are not traditionally considered to be immunogenic. Herein, we review the
      current landscape of anti-PD-1 and anti-PD-L1 therapies in the world of oncology.
      We have performed a comprehensive literature search on the data available through
      PubMed, Medline, Scopus, the ClinicalTrials.gov registry, and abstracts from
      major oncology meetings in order to summarize the clinical data of anti-PD-1/PD
      L1 therapies. 

PMID- 25749123
TI  - Mechanically robust superhydrophobic steel surface with anti-icing, UV
      durability, and corrosion resistance properties.
AB  - A superhydrophobic steel surface was prepared through a facile method: combining
      hydrogen peroxide and an acid (hydrochloric acid or nitric acid) to obtain
      hierarchical structures on steel, followed by a surface modification treatment.
      Empirical grid maps based on different volumes of H2O2/acid were presented,
      revealing a wettability gradient from "hydrophobic" to "rose effect" and finally
      to "lotus effect". Surface grafting has been demonstrated to be realized only on
      the oxidized area. As-prepared superhydrophobic surfaces exhibited excellent anti
      icing properties according to the water-dripping test under overcooled conditions
      and the artificial "steam-freezing" (from 50  degrees C with 90% humidity to the 
      20  degrees C condition) test. In addition, the surfaces could withstand peeling
      with 3M adhesive tape at least 70 times with an applied pressure of 31.2 kPa,
      abrasion by 400 grid SiC sandpaper for 110 cm under 16 kPa, or water impacting
      for 3 h without losing superhydrophobicity, suggesting superior mechanical
      durability. Moreover, outstanding corrosion resistance and UV-durability were
      obtained on the prepared surface. This successful fabrication of a robust, anti
      icing, UV-durable, and anticorrosion superhydrophobic surface could yield a
      prospective candidate for various practical applications. 

PMID- 25749124
TI  - Abundance and distribution of polychlorinated biphenyls (PCBs) in breast tissue.
AB  - Many environmental chemicals accumulate in human tissues and may contribute to
      cancer risk. Polychlorinated biphenyls (PCBs) are associated with adverse health
      effects, but relationships between PCB exposure and breast cancer are unclear. In
      this study, we sought to determine whether bioaccumulation of PCBs differs within
      regions of the human breast and whether PCB levels are associated with clinical
      and pathological characteristics in breast cancer patients. Tissue sections
      (n=245) were collected from breast quadrants from 51 women with a diagnosis
      ranging from disease-free to metastatic breast cancer. Ninety-seven PCB congeners
      were assayed by high resolution gas chromatography. ANOVA was used to examine PCB
      distribution within the breast and relationships with clinical/pathological
      variables. Pearson product-moment correlations assessed relationships between age
      at mastectomy and PCB levels. PCBs were abundant in breast tissues with a median
      concentration of 293.4ng/g lipid (range 15.4-1636.3ng/g). PCB levels in breast
      tissue were significantly different (p<0.001) among functional groupings of
      congeners defined by structure-activity properties: Group I (28.2ng/g), Group II
      (96.6ng/g), Group III (166.0ng/g). Total PCB concentration was highly correlated
      with age at mastectomy, but the distribution of PCBs did not differ by breast
      quadrant. PCB levels were not associated with patient status or tumor
      characteristics. In conclusion, PCB congeners with carcinogenic potential were
      present at high levels in the human breast, but were not associated with clinical
      or pathological characteristics in breast cancer patients. 

PMID- 25749125
TI  - Synergism between exposure to mercury and use of iodine supplements on thyroid
      hormones in pregnant women.
AB  - OBJECTIVE: To evaluate the association between mercury exposure and thyroid
      stimulating hormone (TSH), total triiodothyronine (TT3) and free thyroxine (FT4)
      levels during pregnancy as well as to explore if there is any synergic action
      between mercury and intake of iodine from different sources. METHODS: The study
      population was 1407 pregnant women participating in the Spanish INMA birth cohort
      study. Total mercury concentrations were analyzed in cord blood. Thyroid hormones
      (THs) were measured in serum samples collected at 13.2+/-1.5 weeks of gestation.
      The association between mercury and TH levels was evaluated with multivariate
      linear regression models. Effect modification caused by iodine intake from
      supplements and diet was also evaluated. RESULTS: The geometric means of TSH,
      TT3, FT4 and mercury were 1.1MUU/L, 2.4nmol/L, 10.5pmol/L and 7.7MUg/L,
      respectively. Mercury levels were marginally significantly associated with TT3
      (beta: -0.05; 95%CI: -0.10, 0.01), but were neither associated with TSH nor FT4.
      The inverse association between mercury and TT3 levels was stronger among the
      iodine supplement consumers (-0.08; 95%CI: -0.15, -0.02, interaction p
      value=0.07). The association with FT4 followed the same pattern, albeit not
      significant. CONCLUSION: Prenatal mercury exposure was inversely associated with
      TT3 levels among women who took iodine supplements during pregnancy. These
      results could be of public health concern, although further research is needed.

PMID- 25749126
TI  - Nanoscale copper in the soil-plant system - toxicity and underlying potential
      mechanisms.
AB  - Nanoscale copper particles (nano-Cu) are used in many antimicrobial formulations
      and products for their antimicrobial activity. They may enter deliberately and/or
      accidentally into terrestrial environments including soils. Being the major 'eco
      receptors' of nanoscale particles in the terrestrial ecosystem, soil-microbiota
      and plants (the soil-plant system) have been used as a model to dissect the
      potential impact of these particles on the environmental and human health. In the
      soil-plant system, the plant can be an indirect non-target organism of the soil
      associated nano-Cu that may in turn affect plant-based products and their
      consumers. By all accounts, information pertaining to nano-Cu toxicity and the
      underlying potential mechanisms in the soil-plant system remains scanty,
      deficient and little discussed. Therefore, based on some recent reports from
      (bio)chemical, molecular and genetic studies of nano-Cu versus soil-plant system,
      this article: (i) overviews the status, chemistry and toxicity of nano-Cu in soil
      and plants, (ii) discusses critically the poorly understood potential mechanisms
      of nano-Cu toxicity and tolerance both in soil-microbiota and plants, and (iii)
      proposes future research directions. It appears from studies hitherto made that
      the uncontrolled generation and inefficient metabolism of reactive oxygen species
      through different reactions are the major factors underpinning the overall nano
      Cu consequences in both the systems. However, it is not clear whether the nano-Cu
      or the ion released from it is the cause of the toxicity. We advocate to
      intensify the multi-approach studies focused at a complete characterization of
      the nano-Cu, its toxicity (during life cycles of the least-explored soil
      microbiota and plants), and behavior in an environmentally relevant terrestrial
      exposure setting. Such studies may help to obtain a deeper insight into nano-Cu
      actions and address adequately the nano-Cu-associated safety concerns in the
      'soil-plant system'. 

PMID- 25749127
TI  - Turning univalent stimuli bivalent: Synesthesia can cause cognitive conflict in
      task switching.
AB  - In this study we investigated whether synesthetic color experiences have similar
      effects as real colors in cognitive conflict adaptation. We tested 24 synesthetes
      and two yoke-matched control groups in a task-switching experiment that involved
      regular switches between three simple decision tasks (a color decision, a form
      decision, and a size decision). In most of the trials the stimuli were univalent,
      that is, specific for each task. However, occasionally, black graphemes were
      presented for the size decisions and we tested whether they would trigger
      synesthetic color experiences and thus, turn them into bivalent stimuli. The
      results confirmed this expectation. We were also interested in their effect for
      subsequent performance (i.e., the bivalency effect). The results showed that for
      synesthetic colors the bivalency effect was not as pronounced as for real colors.
      The latter result may be related to differences between synesthetes and controls
      in coping with color conflict. 

PMID- 25749128
TI  - Identification and characterization of a vitamin D3 decomposition product
      bactericidal against Helicobacter pylori.
AB  - This study demonstrated that the vitamin D3 decomposition product VDP1 exerts an
      antibacterial action against Helicobacter pylori but not against other bacteria.
      Treatment with VDP1 induced a collapse of cell membrane structures of H. pylori
      and ultimately lysed the bacterial cells. A unique dimyristoyl
      phosphatidylethanolamine in the membrane lipid compositions contributed to the
      interaction of VDP1 with H. pylori cells. In separate experiments, VDP1 had no
      influence on the viability of the human cancer cell lines MKN45 and T47D and
      lacked any vitamin D3-like hormonal action against the latter. In both (1)H and
      (13)C NMR analyses, the spectra patterns of VDP1 corresponded with those of
      Grundmann's ketone. These results suggest that VDP1 (or Grundmann's ketone-type
      indene compound) may become a fundamental structure for the development of new
      antibacterial substances with selective bactericidal action against H. pylori.

PMID- 25749129
TI  - Cerebrospinal fluid tau levels are a marker for molecular subtype in sporadic
      Creutzfeldt-Jakob disease.
AB  - The molecular subtype of sporadic Creutzfeldt-Jakob disease (sCJD) is an
      important prognostic marker for patient survival. However, subtype determination
      is not possible during lifetime. Because the rate of disease progression is
      associated with the molecular subtype, this study aimed at investigating if total
      tau, a marker of neuronal death, allows premortem diagnosis of molecular subtype
      when codon 129 genotype is known. Two hundred ninety-six sCJD patients were
      tested for their cerebrospinal fluid total tau level at the time of diagnosis and
      were investigated for their sCJD subtype postmortem. There was a significant
      association between tau levels and the prion protein type in patients with codon
      129 MM (p < 0.001), MV (p = 0.004), and VV (p = 0.001) genotype. Receiver
      operating characteristic analyses showed values of area under the curve of 0.76
      0.80 for the different genotypes indicating a good diagnostic validity of the
      test. Total tau can be used as a diagnostic test for the assessment of prion
      protein type when codon 129 genotype is known. It provides valuable information
      for physicians and next of kin about the further course of disease. 

PMID- 25749130
TI  - Physical capacity and risk for long-term sickness absence: a prospective cohort
      study among 8664 female health care workers.
AB  - OBJECTIVE: To assess the prospective associations between self-reported physical
      capacity and risk of long-term sickness absence among female health care workers.
      METHODS: Female health care workers answered a questionnaire about physical
      capacity and were followed in a national register of sickness absence lasting for
      two or more consecutive weeks during 1-year follow-up. Using Cox regression
      hazard ratio analyses adjusted for age, smoking, body mass index, physical
      workload, job seniority, psychosocial work conditions, and previous sickness
      absence, we modeled risk estimates for sickness absence from low and medium
      physical capacity. RESULTS: Low and medium aerobic fitness, low muscle strength,
      low flexibility, and low overall physical capacity significantly increased the
      risk for sickness absence with 20% to 34% compared with health care workers with
      high capacity. CONCLUSIONS: Low physical capacity increases the risk of long-term
      sickness absence among female health care workers.

PMID- 25749131
TI  - Relationship of night and shift work with weight change and lifestyle behaviors.
AB  - OBJECTIVE: To prospectively study the association of night and shift work with
      weight change and lifestyle behaviors. METHODS: Workers participating in the
      Netherlands Working Conditions Cohort Study (2008 and 2009) (N = 5951) reported
      night and shift work, weight and height. Groups included stable night or shift
      work, from day work to night or shift work, from night or shift work to day work,
      and no night or shift work in 2008 and 2009. Regression analyses were used to
      study association changes in night and shift work with weight change and changes
      in lifestyle behaviors. RESULTS: A larger weight change was seen in normal-weight
      workers changing from day to shift work (beta = 0.93%; 95% confidence interval,
      0.01 to 1.85) compared with stable no shift workers. No further associations of
      night and shift work with weight change were observed, neither in normal-weight,
      overweight, and obese workers. CONCLUSIONS: Despite the fact that starting night
      or shift work is associated with some unhealthy lifestyle habits, this study did
      not confirm a positive association of night and shift work with weight change
      over 1 year, except for normal-weight workers moving from day to shift work.

PMID- 25749132
TI  - Effects of an internet-based cognitive behavioral therapy intervention on
      improving work engagement and other work-related outcomes: an analysis of
      secondary outcomes of a randomized controlled trial.
AB  - OBJECTIVE: This study reported a randomized controlled trial of the effectiveness
      of an Internet-based cognitive behavioral therapy (iCBT) program on work
      engagement and secondary work-related outcomes. METHODS: Participants who
      fulfilled the inclusion criteria were randomly allocated to an intervention or a
      control group (N = 381 for each). A 6-week, 6-lesson iCBT program using a Manga
      (Japanese comic) story was provided only to the intervention group. Work
      engagement was assessed at baseline and at 3- and 6-month follow-ups for both
      groups. RESULTS: The iCBT program showed a significant intervention effect on
      work engagement (P = 0.04) with small effect sizes (Cohen's d = 0.16 at 6-month
      follow-up). CONCLUSIONS: The study showed computerized cognitive behavior therapy
      delivered via the Internet to be effective (with a small effect size) in
      increasing work engagement in the general working population. TRIAL REGISTRATION:
      UMIN Clinical Trials Registry (UMIN-CTR) UMIN000006210.

PMID- 25749133
TI  - Change rates and prevalence of a dichotomous variable: simulations and
      applications.
AB  - A common modelling approach in public health and epidemiology divides the
      population under study into compartments containing persons that share the same
      status. Here we consider a three-state model with the compartments: A, B and
      Dead. States A and B may be the states of any dichotomous variable, for example,
      Healthy and Ill, respectively. The transitions between the states are described
      by change rates, which depend on calendar time and on age. So far, a rigorous
      mathematical calculation of the prevalence of property B has been difficult,
      which has limited the use of the model in epidemiology and public health. We
      develop a partial differential equation (PDE) that simplifies the use of the
      three-state model. To demonstrate the validity of the PDE, it is applied to two
      simulation studies, one about a hypothetical chronic disease and one about
      dementia in Germany. In two further applications, the PDE may provide insights
      into smoking behaviour of males in Germany and the knowledge about the ovulatory
      cycle in Egyptian women. 

PMID- 25749134
TI  - Rapid in situ identification of bioactive compounds in plants by in vivo
      nanospray high-resolution mass spectrometry.
AB  - A method for the rapid in situ identification of bioactive compounds in fresh
      plants has been developed using in vivo nanospray coupled to high-resolution mass
      spectrometry (HR-MS). Using a homemade in vivo nanospray ion source, the plant
      liquid was drawn out from a target region and ionized in situ. The ionized
      bioactive compounds were then identified using Q-Orbitrap HR-MS. The accurate
      mass measurements of these bioactive compounds were performed by full-scan or
      selected ion monitoring (SIM), and tandem mass spectrometry (MS/MS) was used in
      the structural elucidation. Without sample pretreatment, 12 bioactive compounds
      in 7 different plant species were identified, namely, isoalliin in onion;
      butylphthalide in celery; N-methylpelletierine, pelletierine, and
      pseudopelletierine in pomegranate; chlorogenic acid in crabapple; solamargine,
      solasonine, and solasodine in nightshade; aloin and aloe-emodin in aloe; and
      menthone in mint. This work demonstrates that in vivo nanospray HR-MS is a good
      method for rapid in situ identification of bioactive compounds in plants. 

PMID- 25749136
TI  - An open chain carboxyethyltin functionalized sandwich-type tungstophosphate based
      on a trivacant Dawson subunit: synthesis, characterization and properties.
AB  - A Dawson sandwich-type polyoxometalate {C(NH2)3}12H4[alphabetabetaalpha
      {(Sn(C3H4O2))2Mn2(P2W15O56)2}].22H2O (abbreviated as SnR-Mn-P2W15),
      functionalized by open chain carboxyethyltin groups, was first prepared in
      aqueous solution under conventional reaction conditions, and then structurally
      characterized by physicochemical and spectroscopic methods. Single crystal X-ray
      diffraction analysis revealed that two Mn(2+) cations and two [Sn(CH2CH2COO)](2+)
      groups are located in the internal and external positions in the so-called
      equatorial region of SnR-Mn-P2W15, respectively. Intriguingly, two exposed
      carboxyl groups act as stretching-arm brackets, which provide a favorable
      structure for potential further functionalization. The electrocatalytic activity
      of SnR-Mn-P2W15 towards the reduction of hydrogen peroxide and nitrite was
      studied. Additionally, its acid catalysis and oxidation catalysis activities in
      organic synthesis were investigated. 

PMID- 25749135
TI  - Pathogenesis of Staphylococcus aureus abscesses.
AB  - Staphylococcus aureus causes many types of human infections and syndromes-most
      notably skin and soft tissue infections. Abscesses are a frequent manifestation
      of S. aureus skin and soft tissue infections and are formed, in part, to contain
      the nidus of infection. Polymorphonuclear leukocytes (neutrophils) are the
      primary cellular host defense against S. aureus infections and a major component
      of S. aureus abscesses. These host cells contain and produce many antimicrobial
      agents that are effective at killing bacteria, but can also cause non-specific
      damage to host tissues and contribute to the formation of abscesses. By
      comparison, S. aureus produces several molecules that also contribute to the
      formation of abscesses. Such molecules include those that recruit neutrophils,
      cause host cell lysis, and are involved in the formation of the fibrin capsule
      surrounding the abscess. Herein, we review our current knowledge of the
      mechanisms and processes underlying the formation of S. aureus abscesses,
      including the involvement of polymorphonuclear leukocytes, and provide a brief
      overview of therapeutic approaches.

PMID- 25749137
TI  - StAR Protein Stability in Y1 and Kin-8 Mouse Adrenocortical Cells.
AB  - The steroidogenic acute regulatory protein (STAR) protein expression is required
      for cholesterol transport into mitochondria to initiate steroidogenesis in the
      adrenal and gonads. STAR is synthesized as a 37 kDa precursor protein which is
      targeted to the mitochondria and imported and processed to an intra-mitochondrial
      30 kDa protein. Tropic hormone stimulation of the cAMP-dependent protein kinase A
      (PKA) signaling pathway is the major contributor to the transcriptional and post
      transcriptional regulation of STAR synthesis. Many studies have focused on the
      mechanisms of cAMP-PKA mediated control of STAR synthesis while there are few
      reports on STAR degradation pathways. The objective of this study was to
      determine the effect of cAMP-PKA-dependent signaling on STAR protein stability.
      We have used the cAMP-PKA responsive Y1 mouse adrenocortical cells and the PKA
      deficient Kin-8 cells to measure STAR phosphorylation and protein half-life.
      Western blot analysis and standard radiolabeled pulse-chase experiments were used
      to determine STAR phosphorylation status and protein half-life, respectively. Our
      data demonstrate that PKA-dependent STAR phosphorylation does not contribute to
      30 kDa STAR protein stability in the mitochondria. We further show that
      inhibition of the 26S proteasome does not block precursor STAR phosphorylation or
      steroid production in Y1 cells. These data suggest STAR can maintain function and
      promote steroidogenesis under conditions of proteasome inhibition. 

PMID- 25749138
TI  - The clinical course of patients with implantable cardioverter-defibrillators:
      Extended experience on clinical outcome, device replacements, and device-related
      complications.
AB  - BACKGROUND: Large randomized trials demonstrated the beneficial effect of
      implantable cardioverter-defibrillator (ICD) and cardiac resynchronization
      therapy-defibrillator (CRT-D) treatments in selected patients. Data on long-term
      follow-up of patients outside the setting of clinical trials are scarce.
      OBJECTIVE: The aim of this study was to evaluate the long-term outcome of ICD and
      CRT-D recipients. METHODS: All patients who underwent ICD (n = 1729 [57%]) or CRT
      D (n = 1326 [43%]) implantation at the Leiden University Medical Center since
      1996 were evaluated. Follow-up visits were performed every 3-6 months, and events
      were registered. Cumulative incidence curves of device therapy and device-related
      complications were adjusted for the competing risk of all-cause mortality.
      RESULTS: After a median follow-up of 5.1 years (25th-75th percentile 3.1-7.8
      years), 842 patients (28%) died. The cumulative incidence of all-cause mortality
      was 49% (95% confidence interval [CI] 45%-54%) in ICD recipients after 12 years
      of follow-up and 55% (95% CI 52%-58%) in CRT-D recipients after 8 years of follow
      up. A total of 1081 patients (35%) received appropriate defibrillator therapy.
      The cumulative incidence of appropriate therapy in ICD patients was 58% (95% CI
      54%-62%) after 12 years of follow-up and 39% (95% CI 35%-43%) in CRT-D patients
      after 8 years of follow-up. Twelve-year cumulative incidences of adverse events
      were 20% (95% CI 18%-22%) for inappropriate shock, 6% (95% CI 5%-8%) for device
      related infection, and 17% (95% CI 14%-21%) for lead failure. CONCLUSION: After
      long-term follow-up of ICD (12 years) and CRT-D (8 years) recipients, 49% of ICD
      recipients and 55% of CRT-D recipients had died. Appropriate ICD therapy was
      received by the majority (58%) of ICD recipients and by almost 40% of CRT-D
      recipients.

PMID- 25749139
TI  - Impact of long-axis function on cardiac surgical outcomes in patients with
      radiation-associated heart disease.
AB  - BACKGROUND: Malignancy-associated thoracic radiation leads to radiation
      associated cardiac disease (RACD) that often necessitates cardiac surgery.
      Myocardial dysfunction is common in patients with RACD. We sought to determine
      the predictive value of global left ventricular ejection fraction and long-axis
      function left ventricular global longitudinal strain (LV-GLS) in such patients.
      METHODS: We studied 163 patients (age, 63 +/- 14 years; 74% women) who had RACD
      and underwent cardiac surgery (20% had reoperations) between 2000 and 2003. In
      addition to standard echocardiography, LV-GLS (%) was derived from the average of
      18 segments in 3 apical views of the left ventricle, using velocity vector
      imaging. Standard clinical and demographic parameters were recorded. All-cause
      mortality was recorded. RESULTS: The mean duration between cardiac surgery and
      the last chest radiation was 18 +/- 12 years. The median European System for
      Cardiac Operative Risk Evaluation (EuroSCORE) was 8, and 88 patients died over
      6.6 +/- 4 years. A total of 52% of patients had >= II+ mitral regurgitation; 23%
      of patients had severe aortic stenosis; and 39% of patients had >= II+ tricuspid
      regurgitation. The mean left ventricular ejection fraction was 54% +/- 13%, and
      the mean LV-GLS was -12.9% +/- 4%. In a Cox proportional survival analysis, lower
      LV-GLS was predictive of mortality in univariable analysis (hazard ratio, 1.07
      (95% confidence interval, 1.01-1.14); P = .006); however, after adjustment for
      other variables, the association became nonsignificant. In patients with a
      EuroSCORE <median, abnormal LV-GLS (<-14.5%) was associated with significantly
      higher mortality (48%), compared with those with normal LV-GLS (32%).
      CONCLUSIONS: In patients who have RACD and undergo cardiac surgery, LV-GLS does
      not sufficiently discriminate and is not independently predictive of long-term
      outcomes. However, in patients with a low EuroSCORE, abnormal LV-GLS was
      associated with higher mortality, compared with those with normal LV-GLS.

PMID- 25749140
TI  - Labetalol, nebivolol, and propranolol relax human radial artery used as coronary
      bypass graft.
AB  - OBJECTIVE: Beta-blockers are a heterogeneous class of agents that are used in the
      treatment of many cardiovascular diseases, especially hypertension and
      atherosclerosis, and that are commonly prescribed after cardiac surgery. In the
      present study, the aim is to investigate the vasorelaxant effects of some common
      beta-adrenoceptor blockers on the human radial artery in vitro, as well as their
      relaxation mechanisms. METHODS: Radial artery rings sourced from human patients
      were mounted in an organ bath and tested for changes in isometric tension in
      relaxation response to labetalol, nebivolol, and propranolol in the presence and
      absence of NG-nitro-L-arginine methyl ester (3 * 10(-5) mol/L) and tetraethyl
      ammonium (3 * 10(-4) mol/L). RESULTS: The labetalol (10(-8) to 10(-4) mol/L),
      nebivolol (10(-8) to 10(-4) mol/L), and propranolol (10(-8) to 10(-4) mol/L)
      induced concentration-dependent relaxations on the radial artery rings, which had
      been precontracted with phenylephrine (10(-6) mol/L). The relaxation response
      induced by labetalol in the isolated radial artery rings was significantly higher
      when compared with the nebivolol and propranolol samples (P < .05). NG-nitro-L
      arginine methyl ester significantly reduced the relaxation of nebivolol (P <
      .05), and tetraethyl ammonium significantly reduced the relaxation of labetalol,
      nebivolol, and propranolol (P < .05). CONCLUSIONS: We speculated that the
      relaxant effect of labetalol, nebivolol, and propranolol was due partly to the
      Ca(2+)-activated K(+) channels. In addition, the relaxation induced by nebivolol
      was largely related with nitric oxide release. Nebivolol, and partly propranolol,
      may provide significant therapeutic benefit, but labetalol can be a good
      alternative for coronary artery bypass grafting with radial artery use.

PMID- 25749141
TI  - Failure-to-rescue: An evolving quality metric.

PMID- 25749142
TI  - Long-term follow-up of a patient with Uhl anomaly after biologic and mechanical
      circulatory support.

PMID- 25749143
TI  - The value of measuring value.

PMID- 25749144
TI  - Cutting corners.

PMID- 25749145
TI  - Antidiabetic and antidyslipidemic activities of aqueous leaf extract of
      Dioscoreophyllum cumminsii (Stapf) Diels in alloxan-induced diabetic rats.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Dioscoreophyllum cumminsii (Stapf) Diels leaves
      are used in the management of diabetics in Nigeria. Thus, the antidiabetic
      activity of aqueous D. cumminsii leaf extract and its capability to halt
      oxidative stress and dyslipidemia in alloxan-induced diabetic rats was
      investigated. METHODOLOGY: Antidiabetic was evaluated in alloxan-induced diabetes
      rats. Diabetic rats were treated with 50, 100 and 200mg/kg body weight of the
      extract. RESULT: The aqueous extract of D. cumminsii leaves significantly reduced
      blood glucose level in a dose dependent manner with highest dose producing 72%
      reduction after 21 days administration, which was compared significantly (P<0.05)
      with the control group and glibenclamide treated groups. Similarly, aqueous
      extract of D. cumminsii significantly reversed reduction in insulin in alloxan
      induced diabetic rats. Alloxan-induced diabetic mediated alterations in liver and
      serum cholesterol, triacylglycerides, high-density lipoprotein cholesterol
      (HDLc), low density lipoprotein cholesterol (LDLc) and very low-density
      lipoprotein cholesterol (VLDLc) were significantly (P<0.05) restored by the
      extract. Aqueous extract of D. cumminsii leaves significantly attenuated the
      decrease in the activities of superoxide dismutase, catalase, glutathione
      peroxidase, glutathione reductase and glucose 6-phosphate dehydrogenase in the
      liver and pancreas of alloxan-induced diabetic rats. Elevation in the
      concentration of malondialdehyde was significantly (P<0.05) lowered by D.
      cumminsii leaves extract. The diabetic-mediated alteration in the architecture of
      liver was alleviated by the extract. CONCLUSION: Overall, aqueous extract of D.
      cumminsii leaves at all doses investigated reduced blood glucose level and
      prevented oxidative stress and dyslipidemia in alloxan-induced diabetic rats.

PMID- 25749146
TI  - Extracellular ATP modulates synaptic plasticity induced by activation of
      metabotropic glutamate receptors in the hippocampus.
AB  - Synaptic plasticity is believed to be a cellular mechanism for memory formation
      in the brain. It has been known that the metabotropic glutamate receptor (mGluR)
      is required for persistent forms of memory and induction of synaptic plasticity.
      Application of mGluR agonists induces synaptic plasticity in the absence of
      electrical conditioning stimulation, such as high or low frequency stimulation.
      The direction of the mGluR-induced synaptic plasticity, i.e., either long-term
      potentiation (LTP) or long-term-depression (LTD), is dependent on whether N
      methyl-D-aspartate receptors (NMDARs) are co-activated with mGluRs. ATP has
      modulatory effects on neuronal functions and, in particular, there is increasing
      evidence that it plays a crucial role in synaptic plasticity. LTP can be induced
      by application of ATP, and this effect is inhibited by NMDAR antagonist. Although
      cooperative effects of NMDARs and mGluRs and of NMDARs and extracellular ATP in
      synaptic plasticity have been revealed, the effect of extracellular ATP on mGluR
      induced synaptic plasticity is unknown. In this article, we summarize published
      data on mGluR- and ATP-induced synaptic plasticity, and present new data showing
      that extracellular ATP facilitates both the LTP and LTD induced by mGluR
      activation. 

PMID- 25749148
TI  - Regulation of mouse chondrocyte differentiation by CCAAT/enhancer-binding
      proteins.
AB  - CCAAT/enhancer-binding protein (C/EBP) beta regulates chondrocyte differentiaion
      and proliferation during endochondral ossification. However, expression and
      function of other C/EBP family members in chondrocytes have not been fully
      understood. To understand the comprehensive regulation of chondrocyte
      differentiation by C/EBPs, we initially examined their expression levels. Among
      four members (C/EBPalpha, C/EBPbeta, C/EBPdelta and C/EBPepsilon) with
      transactivation domain, expression of Cebpb and Cebpd was abundant compared to
      Cebpa, while Cebpe was hardly expressed in mouse isolated chondrocytes.
      Doxycycline (DOX)-inducible overexpression of each of the three C/EBPs
      (C/EBPalpha, C/EBPbeta and C/EBPdelta) in ATDC5 cells suppressed expressions of
      early differentiation markers including Col2a1, aggrecan and Sox9, enhanced those
      of late differentiation markers including Mmp13, Vegfa and Col10a1, and
      decelerated cell proliferation, indicating their overlapped functions in
      chondrocytes. In contrast, DOX-inducible overexpression of A-CEBP, which exerts a
      dominant-negative effect against all C/EBPs, increased expressions of early
      differentiation markers and decreased those of late differentiation markers.
      Finally, microarray and gene ontology analyses showed that A-CEBP altered many
      genes related with various events or tissues such as skeletal development,
      cartilage, cell cycle, inflammation and apoptosis. In conclusion, C/EBPalpha,
      C/EBPbeta and C/EBPdelta regulate proliferation and differentiation of
      chondrocytes and possibly is involved with apoptosis and inflammation. C/EBPs may
      play a variety of roles in the homeostasis of joint cartilage under physiological
      and pathological conditions. 

PMID- 25749147
TI  - Adipose stem cell sheets improved cardiac function in the rat myocardial
      infarction, but did not alter cardiac contractile responses to beta-adrenergic
      stimulation.
AB  - Adipose stem cells (ASCs) are a source of regenerative cells available for
      autologous transplantation to hearts. We compared protective actions of ASC
      sheets on rat myocardial infarction (MI) in comparison with those of skeletal
      myoblast cell sheets. Their effects on infarcted hearts were evaluated by
      biological, histochemical as well as physiological analyses. ASC sheets secreted
      higher concentrations of angiogenic factors (HGF, VEGF, and bFGF; P < 0.05) under
      normoxic and hypoxic conditions than those of myoblast cell sheets, associated
      with reduction of cell apoptosis (P < 0.05). Like myoblast cell sheets, ASC
      sheets improved cardiac function (P < 0.05) and decreased the plasma level of ANP
      (P < 0.05) in MI hearts. ASC sheets restored cardiac remodeling characterized by
      fibrosis, cardiac hypertrophy and impaired angiogenesis (P < 0.05), which was
      associated with increases in angiogenic factors (P < 0.05). In isolated perfused
      rat hearts, ASC sheets improved both systolic and diastolic functions, which was
      comparable to cardiac functions of myoblast cell sheets, while both cell sheets
      failed to restore cardiac contractile response to either isoproterenol,
      pimobendan or dibutyryl cAMP. These results indicated that ASC sheets improved
      cardiac function and remodeling of MI hearts mediated by their paracrine action
      and this improvement was comparable to those by myoblast cell sheets. 

PMID- 25749149
TI  - Characterization of mesenchymal progenitor cells in the crown and root pulp of
      primary teeth.
AB  - The existence of progenitor/mesenchymal stem cells (MSCs) was demonstrated
      previously in human primary/deciduous teeth. In this study, we examined dental
      pulp cells from root portion (root cells) of primary teeth without discernible
      root resorption and compared them with pulp cells from the crown portion (crown
      cells). Root cells and crown cells were characterized and compared to each other
      based on progenitor/MSC characteristics and on their generation efficiency of
      induced pluripotent stem (iPS) cells. Root cells and crown cells included cells
      manifesting typical progenitor/MSC properties such as osteogenic and adipogenic
      differentiation potential and clonogenicity. Interestingly, root cells showed a
      higher expression level of embryonic stem cell marker, KLF4, than crown cells.
      Moreover, the number of colony-forming unit-fibroblast and cell proliferation
      rate were higher for root cells than crown cells, and the efficiency of
      generating iPS cells from root cells was approximately four times higher than
      that from crown cells. Taken together, these results suggest that root cells from
      primary teeth show the MSC-like properties and thus could be a potent alternative
      source for iPS cell generation and the subsequent transplantation therapy. 

PMID- 25749150
TI  - Effect of plantar subcutaneous administration of bergamot essential oil and
      linalool on formalin-induced nociceptive behavior in mice.
AB  - This study investigated the effect of bergamot essential oil (BEO) or linalool, a
      major volatile component of BEO, on the nociceptive response to formalin. Plantar
      subcutaneous injection of BEO or linalool into the ipsilateral hindpaw reduced
      both the first and late phases of the formalin-induced licking and biting
      responses in mice. Plantar subcutaneous injection of BEO or linalool into the
      contralateral hindpaw did not yield an antinociceptive effect, suggesting that
      the antinociceptive effect of BEO or linalool in the formalin test occurred
      peripherally. Intraperitoneal and plantar subcutaneous injection pretreatment
      with naloxone hydrochloride, an opioid receptor antagonist, significantly
      attenuated both BEO- and linalool-induced antinociception. Pretreatment with
      naloxone methiodide, a peripherally acting opioid receptor antagonists, also
      significantly antagonized the antinociceptive effects of BEO and linalool. Our
      results provide evidence for the involvement of peripheral opioids in
      antinociception induced by BEO and linalool. These results suggest that
      activation of peripheral opioid receptors may play an important role in reducing
      formalin-induced nociception.

PMID- 25749151
TI  - Enhancing osteoblast-affinity of titanium scaffolds for bone engineering by use
      of ultraviolet light treatment.
AB  - Ultraviolet (UV) treatment immediately prior to use is attracting attention as an
      effective surface conditioning method for titanium to improve osteoblast
      affinity. The affinity of titanium to osteoblasts in two-dimensional plate
      culture has been well studied, but that in three-dimensional cultures remains
      unclear. Here, we examined the effect of UV treatment on titanium scaffolds,
      comprising micro-thin titanium fibers, used in bone engineering. Titanium
      scaffolds, with and without UV treatment, were seeded with rat bone marrow
      derived osteoblasts, and the number of cells attached to scaffolds and
      osteoblastic phenotype in the cultures were examined. UV treatment improved the
      wettability of scaffolds and significantly reduced the percentage of surface
      carbon. Along with these physicochemical changes in the scaffolds, cell
      attachment increased by a factor of 1.3 as compared to that of the untreated
      control. In addition, alkaline phosphatase activity and calcium deposition
      significantly increased by a factor of 2.3 and 2.0, respectively. Robust
      formation of mineralized structures consisting of clear peaks of calcium and
      phosphorus was observed in the UV-treated scaffolds. The observed increase in
      osteoblast affinity and capability of mineralized matrix formation indicates the
      potential use of UV-treated titanium scaffolds for bone engineering. 

PMID- 25749152
TI  - Bifidobacterium species lower serum glucose, increase expressions of insulin
      signaling proteins, and improve adipokine profile in diabetic mice.
AB  - This study, using C57BL/6J mice with streptozotocin (STZ)-induced diabetes, aimed
      to determine whether Bifidobacterium species (spp.) both induces the expressions
      of proteins in the insulin signaling pathway and enhances the expressions of
      certain adipocytokines. The protein expressions of IkappaB kinase alpha
      (IKKalpha), IkappaB kinase beta (IKKbeta), nuclear factor-kappaB inhibitor alpha
      (IkappaBalpha), and the mitogen-activated protein kinase (MAPK) pathway were also
      investigated. Oral administration of Bifidobacterium spp. reduced blood glucose
      levels significantly and increased the protein expressions of insulin receptor
      beta, insulin receptor substrate 1, protein kinase B (Akt/PKB), IKKalpha, and
      IkappaBalpha. Extracellular-signal-regulated kinase 2 (ERK2) showed increased
      expression. Bifidobacterium spp. also induced the adiponectin expression and
      decreased both macrophage chemoattractant protein-1 (MCP-1) and interleukin-6 (IL
      6) expression. In addition, IKKbeta, c-Jun NH2-terminal kinase (JNK) and p38 MAP
      kinase expressions showed no significant changes in both groups. In conclusion,
      Bifidobacterium spp. may be the promising bacteria for treating diabetes. 

PMID- 25749153
TI  - Characterization of thylakoid lipid membranes from cyanobacteria and higher
      plants by molecular dynamics simulations.
AB  - The thylakoid membrane is mainly composed of non-common lipids, so called
      galactolipids. Despite the importance of these lipids for the function of the
      photosynthetic reaction centers, the molecular organization of these membranes is
      largely unexplored. Here we use multiscale molecular dynamics simulations to
      characterize the thylakoid membrane of both cyanobacteria and higher plants. We
      consider mixtures of up to five different galactolipids plus phosphatidylglycerol
      to represent these complex membranes. We find that the different lipids generally
      mix well, although nanoscale heterogeneities are observed especially in case of
      the plant membrane. The fluidity of the cyanobacterial membrane is markedly
      reduced compared to the plant membrane, even considering elevated temperatures at
      which thermophilic cyanobacteria are found. We also find that the plant membrane
      more readily undergoes a phase transformation to an inverted hexagonal phase. We
      furthermore characterized the conformation and dynamics of the cofactors
      plastoquinone and plastoquinol, revealing of the fast flip-flop rates for the non
      reduced form. Together, our results provide a molecular view on the dynamical
      organization of the thylakoid membrane. 

PMID- 25749154
TI  - Structure and membrane interactions of chionodracine, a piscidin-like
      antimicrobial peptide from the icefish Chionodraco hamatus.
AB  - Chionodracine (Cnd) is a 22-residue peptide of the piscidin family expressed in
      the gills of the Chionodraco hamatus as protection from bacterial infections.
      Here, we report the effects of synthetic Cnd on both Psychrobacter sp. TAD1 and
      Escherichia coli bacteria, as well as membrane models. We found that Cnd
      perforates the inner and outer membranes of Psychrobacter sp. TAD1, making
      discrete pores that cause the cellular content to leak out. Membrane disruption
      studies using intrinsic and extrinsic fluorescence spectroscopy revealed that Cnd
      behaves similarly to other piscidins, with comparable membrane partition
      coefficients. Membrane accessibility assays and structural studies using NMR in
      detergent micelles show that Cnd adopts a canonical topology of antimicrobial
      helical peptides, with the hydrophobic face toward the lipid environment and the
      hydrophilic face toward the bulk solvent. The analysis of Cnd free energy of
      binding to vesicles with different lipid contents indicates a preference for
      charged phospholipids and a more marked binding to native E. coli extracts. Taken
      with previous studies on piscidin-like peptides, we conclude that Cnd first
      adsorbs to the membrane, and then forms pores together with membrane
      fragmentation. Since Cnd has only marginal hemolytic activity, it constitutes a
      good template for developing new antimicrobial agents. 

PMID- 25749156
TI  - Evaluating orbital-ventral medial system regulation of personal attention: a
      critical need for neuropsychological assessment and intervention.
AB  - Attention to self and environment form the basis of effective social exchange and
      relationships. Although implicit in this basic social competency is the ability
      to be self-aware and responsive to the circumstances of others, many
      neuropsychologists have yet to understand or measure its basic functions, let
      alone recognize the brain-behavior relationships that govern this area. Several
      years ago, interest in "emotional intelligence" rose to the forefront of popular
      psychology, but we are still unraveling the cortical, subcortical, and
      neurocellular interactions that produce this nebulous construct, and we are
      determining how dysfunctional frontal-subcortical and cortico-cerebellar
      circuitry can lead to aberrant social dynamics and ultimately psychopathology
      when maladaptive patterns become routinized. In this article, we explore the
      orbital-ventral medial circuitry thought to govern emotional attention, personal
      self-regulation, social concern and exchange, and affective aspects of
      interpersonal relationships. Our examination notes both the dearth of and need
      for neuropsychological research on the biological basis and measurement of
      executive regulation of emotional attention, behavioral regulation, and social
      competence. We conclude with a call for development of neuropsychological
      measures and methods that can foster differential diagnosis and targeted
      treatment strategies for children with orbital-ventral medial circuit
      dysfunction. 

PMID- 25749157
TI  - Correction: Body mass index: accounting for full time sedentary occupation and 24
      hr self-reported time use.

PMID- 25749155
TI  - Bioelectrical regulation of cell cycle and the planarian model system.
AB  - Cell cycle regulation through the manipulation of endogenous membrane potentials
      offers tremendous opportunities to control cellular processes during tissue
      repair and cancer formation. However, the molecular mechanisms by which
      biophysical signals modulate the cell cycle remain underappreciated and poorly
      understood. Cells in complex organisms generate and maintain a constant voltage
      gradient across the plasma membrane known as the transmembrane potential. This
      potential, generated through the combined efforts of various ion transporters,
      pumps and channels, is known to drive a wide range of cellular processes such as
      cellular proliferation, migration and tissue regeneration while its deregulation
      can lead to tumorigenesis. These cellular regulatory events, coordinated by ionic
      flow, correspond to a new and exciting field termed molecular bioelectricity. We
      aim to present a brief discussion on the biophysical machinery involving membrane
      potential and the mechanisms mediating cell cycle progression and cancer
      transformation. Furthermore, we present the planarian Schmidtea mediterranea as a
      tractable model system for understanding principles behind molecular
      bioelectricity at both the cellular and organismal level. This article is part of
      a Special Issue entitled: Membrane channels and transporters in cancers. 

PMID- 25749158
TI  - Induced pluripotent stem cells: from derivation to application in biochemical and
      biomedical research.
AB  - This review considers different methods for obtaining induced pluripotent stem
      (iPS) cells and their use in biochemical and biomedical research. Some viral and
      nonviral methods for obtaining iPS cells are described. Basic factors involved in
      reprogramming are considered. It is also demonstrated that the most suitable
      source of iPS cells are skin fibroblasts. Properties of iPS cells and embryonic
      stem cells are compared, and some advantages of iPS cells for biological and
      biomedical investigations are emphasized. The possibilities for application of
      iPS cells in the development of cell models of some neurodegenerative diseases,
      drug screening, and cell therapy are also considered. 

PMID- 25749159
TI  - Functions of noncoding sequences in mammalian genomes.
AB  - Most of the mammalian genome consists of nucleotide sequences not coding for
      proteins. Exons of genes make up only 3% of the human genome, while the
      significance of most other sequences remains unknown. Recent genome studies with
      high-throughput methods demonstrate that the so-called noncoding part of the
      genome may perform important functions. This hypothesis is supported by three
      groups of experimental data: 1) approximately 10% of the sequences, most of which
      are located in noncoding parts of the genome, is evolutionarily conserved and
      thus can be of functional importance; 2) up to 99% of the mammalian genome is
      being transcribed forming short and long noncoding RNAs in addition to common
      mRNA; and 3) mutations in noncoding parts of the genome can be accompanied by
      progression of pathological states of the organism. In the light of these data,
      in the review we consider the functional role of numerous known sequences of
      noncoding parts of the genome including introns, DNA methylation regions,
      enhancers and locus control regions, insulators, S/MAR sequences, pseudogenes,
      and genes of noncoding RNAs, as well as transposons and simple repeats of
      centromeric and telomeric regions of chromosomes. The assumption is made that the
      intergenic noncoding sequences without definite/clear functions can be involved
      in spatial organization of genetic loci in interphase nuclei. 

PMID- 25749160
TI  - Flagella of halophilic archaea: differences in supramolecular organization.
AB  - Archaeal flagella are similar functionally to bacterial flagella, but
      structurally they are completely different. Helical archaeal flagellar filaments
      are formed of protein subunits called flagellins (archaellins). Notwithstanding
      progress in studies of archaeal flagella achieved in recent years, many problems
      in this area are still unsolved. In this review, we analyze the formation of
      these supramolecular structures by the example of flagellar filaments of
      halophilic archaea. Recent data on the structure of the flagellar filaments
      demonstrate that their supramolecular organization differs considerably in
      different haloarchaeal species. 

PMID- 25749161
TI  - How membrane surface affects protein structure.
AB  - The immediate environment of the negatively charged membrane surface is
      characterized by decreased dielectric constant and pH value. These conditions can
      be modeled by water-alcohol mixtures at moderately low pH. Several globular
      proteins were investigated under these conditions, and their conformational
      behavior in the presence of phospholipid membranes was determined, as well as
      under conditions modeling the immediate environment of the membrane surface.
      These proteins underwent conformational transitions from the native to a molten
      globule-like state. Increased flexibility of the protein structure facilitated
      protein functioning. Our experimental data allow understanding forces that affect
      the structure of a protein functioning near the membrane surface (in other words,
      in the membrane field). Similar conformational states are widely reported in the
      literature. This indicates that the negatively charged membrane surface can serve
      as a moderately denaturing agent in the cell. We conclude that the effect of the
      membrane field on the protein structure must be taken into account. 

PMID- 25749162
TI  - Mechanisms of amyloid fibril formation.
AB  - Amyloid and amyloid-like aggregates are elongated unbranched fibrils consisting
      of beta-structures of separate monomers positioned perpendicular to the fibril
      axis and stacked strictly above each other. In their physicochemical properties,
      amyloid fibrils are reminiscent of synthetic polymers rather than usual proteins
      because they are stable to the action of denaturing agents and proteases. Their
      mechanical stability can be compared to a spider's web, that in spite of its
      ability to stretch, is stronger than steel. It is not surprising that a large
      number of diseases are accompanied with amyloid fibril depositing in different
      organs. Pathologies provoked by depositing of incorrectly folded proteins include
      Alzheimer's, Parkinson's, and Huntington's diseases. In addition, this group of
      diseases involves mucoviscidosis, some types of diabetes, and hereditary
      cataracts. Each type of amyloidosis is characterized by aggregation of a certain
      type of protein that is soluble in general, and thus leads to specific
      distortions of functions of the corresponding organs. Therefore, it is important
      to understand the process of transformation of "native" proteins to amyloid
      fibrils to clarify how these molecules acquire such strength and what key
      elements of this process determine the pathway of erroneous protein folding. This
      review presents our analysis of complied information on the mechanisms of
      formation and biochemical properties of amyloid fibrils. 

PMID- 25749163
TI  - Acid-sensing ion channels and their modulators.
AB  - According to a modern look acid-sensing ion channels (ASICs) are one of the most
      important receptors that perceive pH change in the body. ASICs represent proton
      gated Na+-selective channels, which are expressed in neurons of the central and
      peripheral nervous system. These channels are attracting attention of researchers
      around the world, as they are involved in various physiological processes in the
      body. Drop of pH may occur in tissues in norm (e.g. the accumulation of lactic
      acid, the release of protons upon ATP hydrolysis) and pathology (inflammation,
      ischemic stroke, tissue damage and seizure). These processes are accompanied by
      unpleasant pain sensations, which may be short-lived or can lead to chronic
      inflammatory diseases. Modulators of ASIC channels activity are potential
      candidates for new effective analgesic and neuroprotection drugs. This review
      summarizes available information about structure, function, and physiological
      role of ASIC channels. In addition a description of all known ligands of these
      channels and their practical relevance is provided. 

PMID- 25749164
TI  - Cation-chloride cotransporters: regulation, physiological significance, and role
      in pathogenesis of arterial hypertension.
AB  - This review summarizes the data on the functioning of carriers providing
      electroneutral symport of sodium, potassium, and chloride (Na(+),K(+),2Cl(-)
      cotransport), potassium and chloride (K(+),Cl(-) cotransport), and sodium and
      chloride (K(+),Cl(-) cotransport) as well as molecular mechanisms of the
      regulation of these carriers and their physiological significance. We emphasized
      the involvement of chloride-coupled carriers in the regulation of cell volume and
      intracellular chloride concentration and novel data on the role of ubiquitous
      isoform of Na(+),K(+),2Cl(-) cotransporter NKCC1 in regulation of vascular smooth
      muscle contraction and activity of GABA(A) receptors. Finally, we analyzed the
      data on activation of NKCC1 in patients with essential hypertension and its role
      in the long-term maintenance of elevated systemic blood pressure and myogenic
      response in microcirculatory beds.

PMID- 25749165
TI  - Role of glutathione, glutathione transferase, and glutaredoxin in regulation of
      redox-dependent processes.
AB  - Over the last decade fundamentally new features have been revealed for the
      participation of glutathione and glutathione-dependent enzymes (glutathione
      transferase and glutaredoxin) in cell proliferation, apoptosis, protein folding,
      and cell signaling. Reduced glutathione (GSH) plays an important role in
      maintaining cellular redox status by participating in thiol-disulfide exchange,
      which regulates a number of cell functions including gene expression and the
      activity of individual enzymes and enzyme systems. Maintaining optimum GSH/GSSG
      ratio is essential to cell viability. Decrease in the ratio can serve as an
      indicator of damage to the cell redox status and of changes in redox-dependent
      gene regulation. Disturbance of intracellular GSH balance is observed in a number
      of pathologies including cancer. Consequences of inappropriate GSH/GSSG ratio
      include significant changes in the mechanism of cellular redox-dependent
      signaling controlled both nonenzymatically and enzymatically with the
      participation of isoforms of glutathione transferase and glutaredoxin. This
      review summarizes recent data on the role of glutathione, glutathione
      transferase, and glutaredoxin in the regulation of cellular redox-dependent
      processes. 

PMID- 25749166
TI  - Structural and functional studies of multiheme cytochromes C involved in
      extracellular electron transport in bacterial dissimilatory metal reduction.
AB  - Bacteria utilizing insoluble mineral forms of metal oxides as electron acceptors
      in respiratory processes are widespread in the nature. The electron transfer from
      a pool of reduced quinones in the cytoplasmic membrane across the periplasm to
      the bacterial outer membrane and then to an extracellular acceptor is a key step
      in bacterial dissimilatory metal reduction. Multiheme cytochromes c play a
      crucial role in the extracellular electron transfer. The bacterium Shewanella
      oneidensis MR-1 was used as a model organism to study the mechanism of
      extracellular electron transport. In this review, we discuss recent data on the
      composition, structures, and functions of multiheme cytochromes c and their
      functional complexes responsible for extracellular electron transport in
      Shewanella oneidensis. 

PMID- 25749167
TI  - Diversity of phosphorus reserves in microorganisms.
AB  - Phosphorus compounds are indispensable components of the Earth's biomass
      metabolized by all living organisms. Under excess of phosphorus compounds in the
      environment, microorganisms accumulate reserve phosphorus compounds that are used
      under phosphorus limitation. These compounds vary in their structure and also
      perform structural and regulatory functions in microbial cells. The most common
      phosphorus reserve in microorganism is inorganic polyphosphates, but in some
      archae and bacteria insoluble magnesium phosphate plays this role. Some yeasts
      produce phosphomannan as a phosphorus reserve. This review covers also other
      topics, i.e. accumulation of phosphorus reserves under nutrient limitation,
      phosphorus reserves in activated sludge, mycorrhiza, and the role of mineral
      phosphorus compounds in mammals. 

PMID- 25749168
TI  - Alternative oxidase: distribution, induction, properties, structure, regulation,
      and functions.
AB  - The respiratory chain in the majority of organisms with aerobic type metabolism
      features the concomitant existence of the phosphorylating cytochrome pathway and
      the cyanide- and antimycin A-insensitive oxidative route comprising a so-called
      alternative oxidase (AOX) as a terminal oxidase. In this review, the history of
      AOX discovery is described. Considerable evidence is presented that AOX occurs
      widely in organisms at various levels of organization and is not confined to the
      plant kingdom. This enzyme has not been found only in Archaea, mammals, some
      yeasts and protists. Bioinformatics research revealed the sequences
      characteristic of AOX in representatives of various taxonomic groups. Based on
      multiple alignments of these sequences, a phylogenetic tree was constructed to
      infer their possible evolution. The ways of AOX activation, as well as regulatory
      interactions between AOX and the main respiratory chain are described. Data are
      summarized concerning the properties of AOX and the AOX-encoding genes whose
      expression is either constitutive or induced by various factors. Information is
      presented on the structure of AOX, its active center, and the ubiquinone-binding
      site. The principal functions of AOX are analyzed, including the cases of cell
      survival, optimization of respiratory metabolism, protection against excess of
      reactive oxygen species, and adaptation to variable nutrition sources and to
      biotic and abiotic stress factors. It is emphasized that different AOX functions
      complement each other in many instances and are not mutually exclusive. Examples
      are given to demonstrate that AOX is an important tool to overcome the adverse
      aftereffects of restricted activity of the main respiratory chain in cells and
      whole animals. This is the first comprehensive review on alternative oxidases of
      various organisms ranging from yeasts and protists to vascular plants. 

PMID- 25749169
TI  - Human herpes simplex virus: life cycle and development of inhibitors.
AB  - WHO reports that 90% of human population is infected by different types of
      herpesviruses, which develop latency or cause oral and genital herpes,
      conjunctivitis, eczema herpeticum, and other diseases. Herpesvirus almost always
      accompanies HIV-infection and complicates AIDS treatment. Herpes simplex virus
      type 1 is one of the most wide spread viruses from the Herpesviridae family. HSV
      virion, genome structure, replication mechanisms, antiherpes drug development
      strategies, including design of prodrugs, and mutations causing ACV-resistance in
      clinical HSV isolates are discussed in this review. 

PMID- 25749170
TI  - Improved development of somatic cell cloned mouse embryos by vitamin C and
      latrunculin A.
AB  - Impaired development of embryos produced by somatic cell nuclear transfer (SCNT)
      is mostly associated with faulty reprogramming of the somatic nucleus to a
      totipotent state and can be improved by treatment with epigenetic modifiers. Here
      we report that addition of 100 MUM vitamin C (VitC) to embryo culture medium for
      at least 16 h post-activation significantly increases mouse blastocyst formation
      and, when combined with the use of latrunculin A (LatA) during micromanipulation
      and activation procedures, also development to term. In spite of this, no
      significant effects on pluripotency (OCT4 and NANOG) or nuclear reprogramming
      markers (H3K14 acetylation, H3K9 methylation and DNA methylation and
      hydroxymethylation) could be detected. The use of LatA alone significantly
      improved in vitro development, but not full-term development. On the other hand,
      the simultaneous treatment of cloned embryos with VitC and the histone
      deacetylase inhibitor psammaplin A (PsA), in combination with the use of LatA,
      resulted in cloning efficiencies equivalent to those of VitC or PsA treatments
      alone, and the effects on pluripotency and nuclear reprogramming markers were
      less evident than when only the PsA treatment was applied. These results suggest
      that although both epigenetic modifiers improve cloning efficiencies, possibly
      through different mechanisms, they do not show an additive effect when combined.
      Improvement of SCNT efficiency is essential for its applications in reproductive
      and therapeutic cloning, and identification of molecules which increase this
      efficiency should facilitate studies on the mechanism of nuclear reprogramming
      and acquisition of totipotency. 

PMID- 25749171
TI  - Targeting Glutamatergic Signaling and the PI3 Kinase Pathway to Halt Melanoma
      Progression.
AB  - Our group has previously reported that the majority of human melanomas (>60%)
      express the metabotropic glutamate receptor 1 (GRM1) and that the glutamate
      release inhibitor riluzole, a drug currently used to treat amyotrophic lateral
      sclerosis, can induce apoptosis in GRM1-expressing melanoma cells. Our group
      previously reported that in vitro riluzole treatment reduces cell growth in three
      dimensional (3D) soft agar colony assays by 80% in cells with wildtype
      phosphoinositide 3-kinase (PI3K) pathway activation. However, melanoma cell lines
      harboring constitutive activating mutations of the PI3K pathway (PTEN and NRAS
      mutations) showed only a 35% to 40% decrease in colony formation in soft agar in
      the presence of riluzole. In this study, we have continued our preclinical
      studies of riluzole and its effect on melanoma cells alone and in combination
      with inhibitors of the PI3 kinase pathway: the AKT inhibitor, API-2, and the
      mammalian target of rapamycin (mTOR) inhibitor, rapamycin. We modeled these
      combinatorial therapies on various melanoma cell lines in 3D and 2D systems and
      in vivo. Riluzole combined with mTOR inhibition is more effective at halting
      melanoma anchorage-independent growth and xenograft tumor progression than either
      agent alone. PI3K signaling changes associated with this combinatorial treatment
      shows that 3D (nanoculture) modeling of cell signaling more closely resembles in
      vivo signaling than monolayer models. Riluzole combined with mTOR inhibition is
      effective at halting tumor cell progression independent of BRAF mutational
      status. This makes this combinatorial therapy a potentially viable alternative
      for metastatic melanoma patients who are BRAF WT and are therefore ineligible for
      vemurafenib therapy. 

PMID- 25749172
TI  - Reduced Expression of the Antigen Processing Machinery Components TAP2, LMP2, and
      LMP7 in Tonsillar and Base of Tongue Cancer and Implications for Clinical
      Outcome.
AB  - OBJECTIVES: Patients with human papillomavirus (HPV)-positive tonsillar squamous
      cell carcinoma (TSCC) and base of tongue squamous cell carcinoma (BOTSCC) have a
      better clinical outcome than those with corresponding HPV-negative tumors.
      Moreover, there is a strong positive correlation between absent/low as opposed to
      strong HLA class I expression and favorable clinical outcome for HPV-positive
      tumors, while the reverse applies to HPV-negative tumors. The expression of the
      antigen processing machinery (APM) components TAP1, TAP2, LMP2, and LMP7 in these
      tumors in relation to HPV status, HLA class I expression, each other, and
      clinical outcome was therefore investigated. MATERIAL AND METHODS: Formalin-fixed
      paraffin-embedded TSCC and BOTSCC, derived from 151 patients and previously
      analyzed for HPV DNA, HLA class I, and LMP10 expression were stained by
      immunohistochemistry for TAP1, TAP2, LMP2, and LMP7. RESULTS: Absent/low TAP2,
      LMP2, and LMP7 expression, similar to HLA class I and LMP10, was common in TSCC
      and BOTSCC, irrespective of HPV status. Expression of TAP1 and TAP2 was
      correlated, as was LMP2 to LMP7. LMP2 and LMP7 expression was also associated to
      HLA class I expression. Moreover, absence of LMP7 was linked to increased disease
      free survival in both HPV-positive and HPV-negative cases. CONCLUSION: Reduced
      expression of TAP2, LMP2, and LMP7 was frequent in TSCC and BOTSCC and their
      expression as well as that of TAP1 was often interrelated. Furthermore, low LMP7
      expression correlated to better clinical outcome and may, together with HPV
      status, potentially be used for prediction of treatment response.

PMID- 25749173
TI  - A Meta-Analysis of SMAD4 Immunohistochemistry as a Prognostic Marker in
      Colorectal Cancer.
AB  - AIM: SMAD4 immunohistochemistry is considered a valuable prognostic marker in
      colorectal cancer, but individual studies have often been small and the results
      variable. A meta-analysis could potentially clarify these findings. METHODS: In
      September 2014, a Pubmed and Google Scholar search was conducted to find
      publications that reported the prognostic value of SMAD4 expression. A meta
      analysis was performed to clarify the association between SMAD4 expression and
      survival outcomes. RESULTS: 137 studies were found, of which 13 were considered
      eligible. The studies consisted of a total of 3800 patients. Three different
      endpoints were taken into account, namely, overall survival (OS), disease-free
      survival (DFS), and cancer-specific survival (CSS). In addition, the studies were
      divided into univariate and multivariate analyses. The pooled hazard ratios were
      given as follows: univariate CSS = 1.75 [95% confidence interval (CI): 0.93-3.32;
      z= 1.69; P= .09]; multivariate CSS = 2.17 (95% CI: 1.56-3.01; z= 4.65; P= .000);
      univariate DFS = 2.11 (95% CI: 1.36-3.28; z= 3.32; P= .001); multivariate DFS =
      2.15 (95% CI: 1.56-3.01; z= 4.65; P= .000); univariate OS and DFS = 2.30 (95% CI:
      1.41-3.73; z= 3.36; P= .001); univariate OS = 2.28 (95% CI: 1.30-4.00; z= 2.89;
      P= .004). CONCLUSION: The results of the presented meta-analyses indicate that
      SMAD4 expression status using immunohistochemistry is a prognostic marker for
      patient survival.

PMID- 25749175
TI  - Changing pattern in malignant mesothelioma survival.
AB  - Survival for mesothelioma has been shown to be poor, with marginal improvement
      over time. Recent advances in the understanding of pathophysiology and treatment
      of mesothelioma may impact therapy to improve survival that may not be evident
      from available clinical trials that are often small and not randomized. Therapies
      may affect survival differently based on mesothelioma location (pleural vs
      peritoneal). Data are conflicting regarding the effect of asbestos exposure on
      mesothelioma location. OBJECTIVES: We examined survival in a large cohort of
      mesothelioma subjects analyzed by tumor location and presence and mode of
      asbestos exposure. METHODS: Data were analyzed from cases (n = 380) diagnosed
      with mesothelioma from 1992 to 2012. Cases were either drawn from treatment
      referrals, independent medical evaluation for medical legal purposes, or
      volunteers who were diagnosed with mesothelioma. Subjects completed an
      occupational medical questionnaire, personal interview with the examining
      physician, and physician review of the medical record. RESULTS: This study
      reports better survival for mesothelioma than historical reports. Survival for
      peritoneal mesothelioma was longer than that for pleural mesothelioma (hazard
      ratio = 0.36, 95% confidence interval = 0.24-0.54, P < .001) after adjusting for
      gender and age at diagnosis. Non-occupational cases were more likely to be 1)
      diagnosed with peritoneal mesothelioma, 2) female, 3) exposed, and 4) diagnosed
      at a younger age and to have a 5) shorter latency compared to occupational cases
      (P < .001). CONCLUSION: Peritoneal mesothelioma was more likely associated with
      non-occupational exposure, thus emphasizing the importance of exposure history in
      enhancing early diagnosis and treatment impact.

PMID- 25749174
TI  - Quantitative ultrasound spectroscopic imaging for characterization of disease
      extent in prostate cancer patients.
AB  - Three-dimensional quantitative ultrasound spectroscopic imaging of prostate was
      investigated clinically for the noninvasive detection and extent characterization
      of disease in cancer patients and compared to whole-mount, whole-gland
      histopathology of radical prostatectomy specimens. Fifteen patients with prostate
      cancer underwent a volumetric transrectal ultrasound scan before radical
      prostatectomy. Conventional-frequency (~5MHz) ultrasound images and
      radiofrequency data were collected from patients. Normalized power spectra were
      used as the basis of quantitative ultrasound spectroscopy. Specifically, color
      coded parametric maps of 0-MHz intercept, midband fit, and spectral slope were
      computed and used to characterize prostate tissue in ultrasound images. Areas of
      cancer were identified in whole-mount histopathology specimens, and disease
      extent was correlated to that estimated from quantitative ultrasound parametric
      images. Midband fit and 0-MHz intercept parameters were found to be best
      associated with the presence of disease as located on histopathology whole-mount
      sections. Obtained results indicated a correlation between disease extent
      estimated noninvasively based on midband fit parametric images and that
      identified histopathologically on prostatectomy specimens, with an r(2) value of
      0.71 (P<.0001). The 0-MHz intercept parameter demonstrated a lower level of
      correlation with histopathology. Spectral slope parametric maps offered no
      discrimination of disease. Multiple regression analysis produced a hybrid disease
      characterization model (r(2)=0.764, P<.05), implying that the midband fit
      biomarker had the greatest correlation with the histopathologic extent of
      disease. This work demonstrates that quantitative ultrasound spectroscopic
      imaging can be used for detecting prostate cancer and characterizing disease
      extent noninvasively, with corresponding gross three-dimensional histopathologic
      correlation. 

PMID- 25749176
TI  - Molecular Subgroup Analysis of Clinical Outcomes in a Phase 3 Study of
      Gemcitabine and Oxaliplatin with or without Erlotinib in Advanced Biliary Tract
      Cancer.
AB  - BACKGROUND: We previously reported that the addition of erlotinib to gemcitabine
      and oxaliplatin (GEMOX) resulted in greater antitumor activity and might be a
      treatment option for patients with biliary tract cancers (BTCs). Molecular
      subgroup analysis of treatment outcomes in patients who had specimens available
      for analysis was undertaken. METHODS: Epidermal growth factor receptor (EGFR),
      KRAS, and PIK3CA mutations were evaluated using peptide nucleic acid-locked
      nucleic acid polymerase chain reaction clamp reactions. Survival and response
      rates (RRs) were analyzed according to the mutational status. Sixty-four patients
      (48.1%) were available for mutational analysis in the chemotherapy alone group
      and 61 (45.1%) in the chemotherapy plus erlotinib group. RESULTS: 1.6% (2/116)
      harbored an EGFR mutation (2 patients; exon 20), 9.6% (12/121) harbored a KRAS
      mutation (12 patients; exon 2), and 9.6% (12/118) harbored a PIK3CA mutation (10
      patients, exon 9 and 2 patients, exon 20). The addition of erlotinib to GEMOX in
      patients with KRAS wild-type disease (n = 109) resulted in significant
      improvements in overall response compared with GEMOX alone (30.2% vs 12.5%, P =
      .024). In 95 patients with both wild-type KRAS and PIK3CA, there was evidence of
      a benefit associated with the addition of erlotinib to GEMOX with respect to RR
      as compared with GEMOX alone (P = .04). CONCLUSION: This study demonstrates that
      KRAS mutational status might be considered a predictive biomarker for the
      response to erlotinib in BTCs. Additionally, the mutation status of PIK3CA may be
      a determinant for adding erlotinib to chemotherapy in KRAS wild-type BTCs.

PMID- 25749177
TI  - Targeting mcl-1 for radiosensitization of pancreatic cancers.
AB  - In order to identify targets whose inhibition may enhance the efficacy of
      chemoradiation in pancreatic cancer, we previously conducted an RNAi library
      screen of 8,800 genes. We identified Mcl-1 (myeloid cell leukemia-1), an anti
      apoptotic member of the Bcl-2 family, as a target for sensitizing pancreatic
      cancer cells to chemoradiation. In the present study we investigated Mcl-1
      inhibition by either genetic or pharmacological approaches as a radiosensitizing
      strategy in pancreatic cancer cells. Mcl-1 depletion by siRNA produced
      significant radiosensitization in BxPC-3 and Panc-1 cells in association with
      Caspase-3 activation and PARP cleavage, but only minimal radiosensitization in
      MiaPaCa-2 cells. We next tested the ability of the recently identified,
      selective, small molecule inhibitor of Mcl-1, UMI77, to radiosensitize in
      pancreatic cancer cells. UMI77 caused dissociation of Mcl-1 from the pro
      apoptotic protein Bak and produced significant radiosensitization in BxPC-3 and
      Panc-1 cells, but minimal radiosensitization in MiaPaCa-2 cells.
      Radiosensitization by UMI77 was associated with Caspase-3 activation and PARP
      cleavage. Importantly, UMI77 did not radiosensitize normal small intestinal
      cells. In contrast, ABT-737, an established inhibitor of Bcl-2, Bcl-XL, and Bcl
      w, failed to radiosensitize pancreatic cancer cells suggesting the unique
      importance of Mcl-1 relative to other Bcl-2 family members to radiation survival
      in pancreatic cancer cells. Taken together, these results validate Mcl-1 as a
      target for radiosensitization of pancreatic cancer cells and demonstrate the
      ability of small molecules which bind the canonical BH3 groove of Mcl-1, causing
      displacement of Mcl-1 from Bak, to selectively radiosensitize pancreatic cancer
      cells. 

PMID- 25749178
TI  - Determining the Variability of Lesion Size Measurements from CT Patient Data Sets
      Acquired under "No Change" Conditions.
AB  - PURPOSE: To determine the variability of lesion size measurements in computed
      tomography data sets of patients imaged under a "no change" ("coffee break")
      condition and to determine the impact of two reading paradigms on measurement
      variability. METHOD AND MATERIALS: Using data sets from 32 non-small cell lung
      cancer patients scanned twice within 15 minutes ("no change"), measurements were
      performed by five radiologists in two phases: (1) independent reading of each
      computed tomography dataset (timepoint): (2) a locked, sequential reading of
      datasets. Readers performed measurements using several sizing methods, including
      one-dimensional (1D) longest in-slice dimension and 3D semi-automated segmented
      volume. Change in size was estimated by comparing measurements performed on both
      timepoints for the same lesion, for each reader and each measurement method. For
      each reading paradigm, results were pooled across lesions, across readers, and
      across both readers and lesions, for each measurement method. RESULTS: The mean
      percent difference (+/-SD) when pooled across both readers and lesions for 1D and
      3D measurements extracted from contours was 2.8 +/- 22.2% and 23.4 +/- 105.0%,
      respectively, for the independent reads. For the locked, sequential reads, the
      mean percent differences (+/-SD) reduced to 2.52 +/- 14.2% and 7.4 +/- 44.2% for
      the 1D and 3D measurements, respectively. CONCLUSION: Even under a "no change"
      condition between scans, there is variation in lesion size measurements due to
      repeat scans and variations in reader, lesion, and measurement method. This
      variation is reduced when using a locked, sequential reading paradigm compared to
      an independent reading paradigm.

PMID- 25749179
TI  - Mxi1 and mxi1-0 antagonize N-myc function and independently mediate apoptosis in
      neuroblastoma.
AB  - Neuroblastoma (NB) is the third most common malignancy of childhood, and outcomes
      for children with advanced disease remain poor; amplification of the MYCN gene
      portends a particularly poor prognosis. Mxi1 antagonizes N-Myc by competing for
      binding to Max and E-boxes. Unlike N-Myc, Mxi1 mediates transcriptional
      repression and suppresses cell proliferation. Mxi1 and Mxi1-0 (an alternatively
      transcribed Mxi1 isoform) share identical Max and DNA binding domains but differ
      in amino-terminal sequences. Because of the conservation of these critical
      binding domains, we hypothesized that Mxi1-0 antagonizes N-Myc activity similar
      to Mxi1. SHEP NB cells and SHEP cells stably transfected with MYCN (SHEP/MYCN)
      were transiently transfected with vectors containing full-length Mxi1, full
      length Mxi1-0, or the common Mxi domain encoded by exons 2 to 6 (ex2-6). After
      incubation in low serum, parental SHEP/MYCN cell numbers were reduced compared
      with SHEP cells. Activated caspase-3 staining and DNA fragmentation ELISA
      confirmed that SHEP/MYCN cells undergo apoptosis in low serum, while SHEP/MYCN
      cells transfected with Mxi1 or Mxi1-0 do not. However, SHEP/MYCN cells
      transfected with Mxi1 or Mxi1-0 and grown in normal serum showed proliferation
      rates similar to SHEP cells. Mxi ex2-6 did not affect cell number in low or
      normal serum, suggesting that amino terminal domains of Mxi1 and Mxi1-0 are
      critical for antagonism. In the absence of N-Myc, Mxi1 and Mxi1-0 induce
      apoptosis independently through the caspase-8-dependent extrinsic pathway, while
      N-Myc activates the caspase-9-dependent intrinsic pathway. Together, these data
      indicate that Mxi1 and Mxi1-0 antagonize N-Myc but also independently impact NB
      cell survival. 

PMID- 25749180
TI  - Gender gap in medicine: only one woman councilor in the Japan Surgical Society.
AB  - Japan ranks low in the global gender gap index. Academic promotion is difficult
      for women doctors, and the leaky pipeline of women doctors is evident in academic
      medicine. The Japan Surgical Society (JSS) has 2,874 (7.2% of total membership)
      female members as of April 2014. The total number of councilors in JSS has
      increased, but there is still only one female member on the Council. The fact
      that there are so few women in decision-making positions makes it challenging to
      fight for equality. The Japanese Association of Medical Science (JAMS) is an
      association with exclusive institutional membership comprising the major medical
      societies in Japan, and currently has a membership of 122 specialist medical
      societies. It is essential to have at least one female committee member in each
      committee of the JAMS, which would provide opportunities to establish career
      paths for women doctors, to make rules that suit the lifestyle of women doctors,
      and to improve work-life balance. 

PMID- 25749181
TI  - Study of early stages of amyloid Abeta13-23 formation using molecular dynamics
      simulation in implicit environments.
AB  - beta-amyloid aggregation and formation of senile plaques is one of the hallmarks
      of Alzheimer's disease (AD). It leads to degeneration of neurons and decline of
      cognitive functions. The most aggregative and toxic form of beta-amyloid is
      Abeta1-42 but in experiments, the shorter forms able to form aggregates are also
      used. The early stages of amyloid formation are of special interest due to the
      influence of this peptide on progression of AD. Here, we employed nine helices of
      undecapeptide Abeta13-23 and studied progress of amyloid formation using 500ns
      molecular dynamics simulation and implicit membrane environment. The small beta
      sheets emerged very early during simulation as separated two-strand structures
      and a presence of the membrane facilitated this process. Later, the larger beta
      sheets were formed. However, the ninth helix which did not form paired structure
      stayed unchanged till the end of MD simulation. Paired helix-helix interactions
      seemed to be a driving force of beta-sheet formation at early stages of amyloid
      formation. Contrary, the specific interactions between alpha-helix and beta-sheet
      can be very stable and be stabilized by the membrane. 

PMID- 25749182
TI  - Adaptive myoelectric pattern recognition toward improved multifunctional
      prosthesis control.
AB  - The non-stationary property of electromyography (EMG) signals in real life
      settings usually hinders the clinical application of the myoelectric pattern
      recognition for prosthesis control. The classical EMG pattern recognition
      approach consists of two separate steps: training and testing, without
      considering the changes between training and testing data induced by electrode
      shift, fatigue, impedance changes and psychological factors, and often results in
      performance degradation. The aim of this study was to develop an adaptive
      myoelectric pattern recognition system, aiming to retrain the classifier online
      with the testing data without supervision, providing a self-correction mechanism
      for suppressing misclassifications. This paper presents an adaptive unsupervised
      classifier based on support vector machine (SVM) to improve the classification
      performance. Experimental data from 15 healthy subjects were used to evaluate
      performance. Preliminary study on intra-session and inter-session EMG data was
      conducted to verify the performance of the unsupervised adaptive SVM classifier.
      The unsupervised adaptive SVM classifier outperformed the conventional SVM by
      3.3% and 8.0% for the combination of time-domain and autoregressive features in
      the intra-session and inter-session tests, respectively. The proposed approach is
      capable of incorporating the useful information in testing data to the
      classification model by taking into account the overtime changes in the testing
      data with respect to the training data to retrain the original classifier,
      therefore providing a self-correction mechanism for suppressing
      misclassifications. 

PMID- 25749184
TI  - Coupled within-host and between-host dynamics and evolution of virulence.
AB  - Mathematical models coupling within- and between-host dynamics can be helpful for
      deriving trade-off functions between disease transmission and virulence at the
      population level. Such functions have been used to study the evolution of
      virulence and to explore the possibility of a conflict between natural selection
      at individual and population levels for directly transmitted diseases (Gilchrist
      and Coombs, 2006). In this paper, a new coupled model for environmentally-driven
      diseases is analyzed to study similar biological questions. It extends the model
      in Cen et al. (2014) and Feng et al. (2013) by including the disease-induced host
      mortality. It is shown that the extended model exhibits similar dynamical
      behaviors including the possible occurrence of a backward bifurcation. It is also
      shown that the within-host pathogen load and the disease prevalence at the
      positive stable equilibrium are increasing functions of the within- and between
      host reproduction numbers (Rw0 and Rb0), respectively. Optimal parasite
      strategies will maximize these reproduction numbers at the two levels, and a
      conflict may exist between the two levels. Our results highlight the role of
      inter-dependence of variables and parameters in the fast and slow systems for
      persistence of infections and evolution of pathogens in an environmentally-driven
      disease. Our results also demonstrate the importance of incorporating explicit
      links of the within- and between-host dynamics into the computation of threshold
      conditions for disease control. 

PMID- 25749183
TI  - Translocase of inner mitochondrial membrane 44 alters the mitochondrial fusion
      and fission dynamics and protects from type 2 diabetes.
AB  - OBJECTIVE: In obesity and type 2 diabetes, the impairment of mitochondrial
      function in white adipose tissue (WAT) is linked to a reduction in whole body
      insulin sensitivity. Timm44 is upregulated in the kidneys of streptozotocin
      induced diabetic mice. In the inner mitochondrial membrane, Timm44 anchors
      mitochondrial heat-shock protein 70 (mtHsp70) to the translocase of inner
      mitochondrial membrane 23 (TIM23) complex and facilitates the import of
      mitochondria-targeted preproteins into the mitochondrial matrix dependent on the
      inner membrane potential and ATP hydrolysis on ATPase domain of mtHsp70. METHODS:
      We generated the aP2-promoter driven Timm44 transgenic (Tg) mouse model and
      investigated whether Timm44 Tg mice fed high-fat/high-sucrose (HFHS) chow are
      protected from type 2 diabetes and obesity. RESULTS: The body weight of aP2
      promoter driven Timm44 Tg mice was lower than that of wild type mice, and insulin
      sensitivity was greater in Timm44 Tg mice than in wild type mice. Although WAT
      weight was not altered in Timm44 Tg mice fed HFHS chow, adipocyte size was
      reduced, and mitochondrial fusion associated with decreased expression of fission
      genes, such as Dnm1l and Fis1, was observed. In addition, when fed standard (STD)
      chow, the expressions of the fusion genes Opa1, Mfn1 and Mfn2, and Mfn1 were
      significantly increased in Timm44 Tg mice compared to wild type mice, and fused
      mitochondria were also observed in Timm44 Tg mice fed STD chow. CONCLUSIONS: The
      Timm44 gene may be a new target for the treatment of type 2 diabetes.

PMID- 25749185
TI  - Mathematical model of the effect of ischemia-reperfusion on brain capillary
      collapse and tissue swelling.
AB  - Restoration of an adequate cerebral blood supply after an ischemic attack is a
      primary clinical goal. However, the blood-brain barrier may break down after a
      prolonged ischemia causing the fluid in the blood plasma to filtrate and
      accumulate into the cerebral tissue interstitial space. Accumulation of this
      filtration fluid causes the cerebral tissue to swell, a condition known as
      vasogenic oedema. Tissue swelling causes the cerebral microvessels to be
      compressed, which may further obstruct the blood flow into the tissue, thus
      leading to the no-reflow phenomenon or a secondary ischemic stroke. The actual
      mechanism of this however is still not fully understood. A new model is developed
      here to study the effect of reperfusion on the formation of vasogenic oedema and
      cerebral microvessel collapse. The formation of vasogenic oedema is modelled
      using the capillary filtration equation while vessel collapse is modelled using
      the tube law of microvessel. Tissue swelling is quantified in terms of
      displacement, which is modelled using poroelastic theory. The results show that
      there is an increase in tissue displacement and interstitial pressure after
      reperfusion. In addition, the results also show that vessel collapse can occur at
      high value of reperfusion pressure, low blood osmotic pressure, high cerebral
      capillary permeability and low cerebral capillary stiffness. This model provides
      insight on the formation of ischemia-reperfusion injury by tissue swelling and
      vessel collapse. 

PMID- 25749186
TI  - [T. Bultez in reply to the article by M. Constant. Nuchal translucency: not so
      simple! Gynecol Obstet Fertil 2014; 42: 820-821].

PMID- 25749187
TI  - [Satisfaction in ambulatory patients with breast-conserving surgery and sentinel
      node biopsy for breast cancer].
AB  - OBJECTIVE: The objective of this study was to evaluate outpatient satisfaction
      for breast cancer surgery and compare with inpatient satisfaction. PATIENTS AND
      METHODS: Our observational prospective study included all patients who underwent
      breast cancer surgical procedure (breast-conserving surgery and sentinel node
      biopsy) between July and December 2013 in a cancer center. Patients were asked to
      answer a questionnaire at discharge and 30 days after surgery. RESULTS: One
      hundred and fifty-five patients (exclusively women) were included; the outpatient
      group comprised 102 patients and the inpatient group 53. The study showed no
      statistical difference in patients' satisfaction betweeen the two groups at
      discharge (P=0.20) and 30 days after surgery (P=0.30); 101 (99%) outpatients and
      44 (95.7%) inpatients had very good or excellent level of satisfaction at
      discharge and 88 (92,7%) and 49 (98%), respectively 30 days after surgery. The
      overall mean satisfaction score was 9.1+/-1.2 [3-10] at discharge and 8.7+/-1.3
      [3-10] 30 days after surgery. DISCUSSION AND CONCLUSION: Our study found high
      degree of satisfaction after breast surgery for cancer both for outpatients and
      inpatients. This suggests that ambulatory surgery is possible and valid for this
      type of oncologic breast surgery.

PMID- 25749188
TI  - Deferoxamine reduces intracerebral hemorrhage-induced white matter damage in aged
      rats.
AB  - Iron contributes to c-Jun N-terminal kinases (JNK) activation in young rats and
      white matter injury in piglets after intracerebral hemorrhage (ICH). In the
      present study, we examined the effect of deferoxamine on ICH-induced white matter
      injury and JNK activation and in aged rats. Male Fischer 344 rats (18months old)
      had either an intracaudate injection of 100MUl of autologous blood or a needle
      insertion (sham). The rats were treated with deferoxamine or vehicle with
      different regimen (dosage, duration and time window). White matter injury and
      activation of JNK were examined. We found that a dose of DFX should be at more
      than 10mg/kg for a therapeutic duration more than 2days with a therapeutic time
      window of 12h to reduce ICH-induced white matter loss at 2months. ICH-induced
      white matter injury was associated with JNK activation. The protein levels of
      phosphorylated-JNK (P-JNK) were upregulated at day-1 after ICH and then gradually
      decreased. P-JNK immunoreactivity was mostly located in white matter bundles. ICH
      induced JNK activation was reduced by DFX treatment. This study demonstrated that
      DFX can reduce ICH-induced JNK activation and white matter damage. 

PMID- 25749189
TI  - PI3Kgamma deficiency enhances seizures severity and associated outcomes in a
      mouse model of convulsions induced by intrahippocampal injection of pilocarpine.
AB  - Phosphatidylinositol 3-kinase (PI3K) is an enzyme involved in different
      pathophysiological processes, including neurological disorders. However, its role
      in seizures and postictal outcomes is still not fully understood. We investigated
      the role of PI3Kgamma on seizures, production of neurotrophic and inflammatory
      mediators, expression of a marker for microglia, neuronal death and hippocampal
      neurogenesis in mice (WT and PI3Kgamma(-/-)) subjected to intrahippocampal
      microinjection of pilocarpine. PI3Kgamma(-/-) mice presented a more severe status
      epilepticus (SE) than WT mice. In hippocampal synaptosomes, genetic or
      pharmacological blockade of PI3Kgamma enhanced the release of glutamate and the
      cytosolic calcium concentration induced by KCl. There was an enhanced neuronal
      death and a decrease in the doublecortin positive cells in the dentate gyrus of
      PI3Kgamma(-/-) animals after the induction of SE. Levels of BDNF were
      significantly increased in the hippocampus of WT and PI3Kgamma(-/-) mice,
      although in the prefrontal cortex, only PI3Kgamma(-/-) animals showed significant
      increase in the levels of this neurotrophic factor. Pilocarpine increased
      hippocampal microglial immunolabeling in both groups, albeit in the prelimbic,
      medial and motor regions of the prefrontal cortex this increase was observed only
      in PI3Kgamma(-/-) mice. Regarding the levels of inflammatory mediators,
      pilocarpine injection increased interleukin (IL) 6 in the hippocampus of WT and
      PI3Kgamma(-/-) animals and in the prefrontal cortex of PI3Kgamma(-/-) animals 24h
      after the stimulus. Levels of TNFalpha were enhanced in the hippocampus and
      prefrontal cortex of only PI3Kgamma(-/-) mice at this time point. On the other
      hand, PI3Kgamma deletion impaired the increase in IL-10 in the hippocampus
      induced by pilocarpine. In conclusion, the lack of PI3Kgamma revealed a
      deleterious effect in an animal model of convulsions induced by pilocarpine,
      suggesting that this enzyme may play a protective role in seizures and
      pathological outcomes associated with this condition. 

PMID- 25749190
TI  - Mirror-image pain after nerve reconstruction in rats is related to enhanced
      density of epidermal peptidergic nerve fibers.
AB  - Mirror-image pain is a phenomenon in which unprovoked pain is detected on the
      uninjured contralateral side after unilateral nerve injury. Although it has been
      implicated that enhanced production of nerve growth factor (NGF) in the
      contralateral dorsal root ganglion is important in the development of mirror
      image pain, it is not known if this is related to enhanced expression of
      nociceptive fibers in the contralateral skin. Mechanical and thermal sensitivity
      in the contralateral hind paw was measured at four different time points (5, 10,
      20 and 30weeks) after transection and immediate end-to-end reconstruction of the
      sciatic nerve in rats. These findings were compared to the density of epidermal
      (peptidergic and non-peptidergic) nerve fibers on the contralateral hind paw.
      Mechanical hypersensitivity of the contralateral hind paw was observed at 10weeks
      PO, a time point in which both subgroups of epidermal nerve fibers reached
      control values. Thermal hypersensitivity was observed with simultaneous increase
      in the density of epidermal peptidergic nerve fibers of the contralateral hind
      paw at 20weeks PO. Both thermal sensitivity and the density of epidermal nerve
      fibers returned to control values 30weeks PO. We conclude that changes in skin
      innervation and sensitivity are present on the uninjured corresponding side in a
      transient pain model. Therefore, the contralateral side cannot serve as control.
      Moreover, the current study confirms the involvement of the peripheral nervous
      system in the development of mirror-image pain. 

PMID- 25749191
TI  - Cardiomyocyte Regeneration in the mdx Mouse Model of Nonischemic Cardiomyopathy.
AB  - Endogenous regeneration has been demonstrated in the mammalian heart after
      ischemic injury. However, approximately one-third of cases of heart failure are
      secondary to nonischemic heart disease and cardiac regeneration in these cases
      remains relatively unexplored. We, therefore, aimed at quantifying the rate of
      new cardiomyocyte formation at different stages of nonischemic cardiomyopathy.
      Six-, 12-, 29-, and 44-week-old mdx mice received a 7 day pulse of BrdU.
      Quantification of isolated cardiomyocyte nuclei was undertaken using cytometric
      analysis to exclude nondiploid nuclei. Between 6-7 and 12-13 weeks, there was a
      statistically significant increase in the number of BrdU-labeled nuclei in the
      mdx hearts compared with wild-type controls. This difference was lost by the 29
      30 week time point, and a significant decrease in cardiomyocyte generation was
      observed in both the control and mdx hearts by 44-45 weeks. Immunohistochemical
      analysis demonstrated BrdU-labeled nuclei exclusively in mononucleated
      cardiomyocytes. This study demonstrates cardiomyocyte regeneration in a
      nonischemic model of mammalian cardiomyopathy, controlling for changes in nuclear
      ploidy, which is lost with age, and confirms a decrease in baseline rates of
      cardiomyocyte regeneration with aging. While not attempting to address the
      cellular source of regeneration, it confirms the potential utility of innate
      regeneration as a therapeutic target. 

PMID- 25749192
TI  - Model study of enhanced oil recovery by flooding with aqueous surfactant solution
      and comparison with theory.
AB  - With the aim of elucidating the details of enhanced oil recovery by surfactant
      solution flooding, we have determined the detailed behavior of model systems
      consisting of a packed column of calcium carbonate particles as the porous rock,
      n-decane as the trapped oil, and aqueous solutions of the anionic surfactant
      sodium bis(2-ethylhexyl) sulfosuccinate (AOT). The AOT concentration was varied
      from zero to above the critical aggregation concentration (cac). The salt content
      of the aqueous solutions was varied to give systems of widely different, post-cac
      oil-water interfacial tensions. The systems were characterized in detail by
      measuring the permeability behavior of the packed columns, the adsorption
      isotherms of AOT from the water to the oil-water interface and to the water
      calcium carbonate interface, and oil-water-calcium carbonate contact angles.
      Measurements of the percent oil recovery by pumping surfactant solutions into
      calcium carbonate-packed columns initially filled with oil were analyzed in terms
      of the characterization results. We show that the measured contact angles as a
      function of AOT concentration are in reasonable agreement with those calculated
      from values of the surface energy of the calcium carbonate-air surface plus the
      measured adsorption isotherms. Surfactant adsorption onto the calcium carbonate
      water interface causes depletion of its aqueous-phase concentration, and we
      derive equations which enable the concentration of nonadsorbed surfactant within
      the packed column to be estimated from measured parameters. The percent oil
      recovery as a function of the surfactant concentration is determined solely by
      the oil-water-calcium carbonate contact angle for nonadsorbed surfactant
      concentrations less than the cac. For surfactant concentrations greater than the
      cac, additional oil removal occurs by a combination of solubilization and
      emulsification plus oil mobilization due to the low oil-water interfacial tension
      and a pumping pressure increase. 

PMID- 25749193
TI  - Fear of stimulant therapy for children and adolescents with attention
      deficit/hyperactivity disorder.

PMID- 25749194
TI  - eIF2alpha phosphorylation as a biomarker of immunogenic cell death.
AB  - Cancer cells exposed to some forms of chemotherapy and radiotherapy die while
      eliciting an adaptive immune response. Such a functionally peculiar variant of
      apoptosis has been dubbed immunogenic cell death (ICD). One of the central events
      in the course of ICD is the activation of an endoplasmic reticulum (ER) stress
      response. This is instrumental for cells undergoing ICD to emit all the signals
      that are required for their demise to be perceived as immunogenic by the host,
      and culminates with the phosphorylation of eukaryotic translation initiation
      factor 2alpha (eIF2alpha). In particular, eIF2alpha phosphorylation is required
      for the pre-apoptotic exposure of the ER chaperone calreticulin (CALR) on the
      cell surface, which is a central determinant of ICD. Importantly, phosphorylated
      eIF2alpha can be quantified in both preclinical and clinical samples by
      immunoblotting or immunohistochemistry using phosphoneoepitope-specific
      monoclonal antibodies. Of note, the phosphorylation of eIF2alpha and CALR
      exposure do not necessarily correlate with each other, and neither of these
      parameters is sufficient for cell death to be perceived as immunogenic.
      Nonetheless, accumulating data indicate that assessing the degree of
      phosphorylation of eIF2alpha provides a convenient parameter to monitor ICD.
      Here, we discuss the role of the ER stress response in ICD and the potential
      value of eIF2alpha phosphorylation as a biomarker for this clinically relevant
      variant of apoptosis. 

PMID- 25749196
TI  - Effects of rivaroxaban versus warfarin on hospitalization days and other health
      care resource utilization in patients with nonvalvular atrial fibrillation: an
      observational study from a cohort of matched users.
AB  - PURPOSE: Compared with warfarin, the new target-specific oral anticoagulant
      agents may have advantages, such as shorter hospital length of stay, in patients
      with nonvalvular atrial fibrillation (NVAF). The objective of the present study
      was to assess, among patients with NVAF, the effects of rivaroxaban versus
      warfarin on the number of hospitalization days and other health care resource
      utilization in a cohort of rivaroxaban users and matched warfarin users. METHODS:
      Data from health care claims dated from May 2011 to December 2012 from the Humana
      database were analyzed. Adult patients newly initiated on treatment with
      rivaroxaban or warfarin, with >=2 diagnoses of AF (ICD-9-CM code 427.31), and
      without valvular AF were identified. Based on propensity score methods, warfarin
      recipients were matched 1:1 to rivaroxaban recipients. The end of the observation
      period was defined as the end of data availability, the end of insurance
      coverage, death, the date of a switch to another anticoagulant agent, or day 14
      of treatment nonpersistence. The total number of hospitalization days and other
      health care resource utilization parameters (numbers of hospitalizations,
      emergency department [ED] visits, and outpatient visits) were evaluated using the
      method by Lin et al. FINDINGS: Matches for all rivaroxaban recipients were found,
      and the characteristics of the matched groups (n = 2253 per group) were well
      balanced. The mean age of both cohorts was 74 years; 46% were female. The
      estimated mean total numbers of hospitalization days were significantly less in
      rivaroxaban users compared with those in warfarin users (all-cause, 2.71 vs 3.87
      days [P = 0.032]; AF-related, 2.11 vs 3.02 days [P = 0.014]). The numbers of
      outpatient visits were also significantly less (all-cause, 25.26 vs 35.79 visits
      [P < 0.001]; AF-related, 5.48 vs 9.06 visits [P < 0.001]). Rivaroxaban users had
      a lesser estimated mean number of all-cause hospitalizations compared with
      warfarin users (0.55 vs 0.73; P = 0.084), and a significantly lesser estimated
      mean number of AF-related hospitalizations (0.40 vs 0.57; P = 0.022). The
      difference in the estimated mean numbers of all-cause ED visits was not
      statistically significant between the rivaroxaban and warfarin users.
      IMPLICATIONS: In this study conducted in clinical practice, the estimated mean
      numbers of hospitalization days, outpatient visits, and AF-related
      hospitalizations associated with rivaroxaban were significantly less than were
      those associated with warfarin in these patients with NVAF. The corresponding
      estimated difference in all-cause ED visits was not statistically significant.

PMID- 25749197
TI  - Behavioural, hormonal and neurobiological mechanisms of aggressive behaviour in
      human and nonhuman primates.
AB  - Aggression is a key component for social behaviour and can have an adaptive value
      or deleterious consequences. Here, we review the role of sex-related differences
      in aggressive behaviour in both human and nonhuman primates. First, we address
      aggression in primates, which varies deeply between species, both in intensity
      and in display, ranging from animals that are very aggressive, such as
      chimpanzees, to the nonaggressive bonobos. Aggression also influences the
      hierarchical structure of gorillas and chimpanzees, and is used as the main tool
      for dealing with other groups. With regard to human aggression, it can be
      considered a relevant adaptation for survival or can have negative impacts on
      social interaction for both sexes. Gender plays a critical role in aggressive and
      competitive behaviours, which are determined by a cascade of physiological
      changes, including GABAergic and serotonergic systems, and sex neurosteroids. The
      understanding of the neurobiological bases and behavioural determinants of
      different types of aggression is fundamental for minimising these negative
      impacts. 

PMID- 25749198
TI  - Evaluation of potential gender-related differences in behavioral and cognitive
      alterations following pilocarpine-induced status epilepticus in C57BL/6 mice.
AB  - Together with pharmacoresistant seizures, the quality of life of temporal lobe
      epilepsy (TLE) patients is negatively impacted by behavioral comorbidities
      including but not limited to depression, anxiety and cognitive deficits. The
      pilocarpine model of TLE has been widely used to study characteristics of human
      TLE, including behavioral comorbidities. Since the outcomes of pilocarpine
      induced TLE might vary depending on several experimental factors, we sought to
      investigate potential gender-related differences regarding selected behavioral
      alterations in C57BL6 mice. We found that epileptic mice, independent of gender,
      displayed increased anxiety-like behavior in the open-field test. In the object
      recognition test, epileptic mice, regardless of gender, showed a decreased
      recognition index at 24 (but not at 4) hours after training. On the other hand,
      no significant differences were found regarding mice learning and memory
      performance in the Barnes maze paradigm. Motor coordination and balance as
      assessed by the beam walk and rotarod tests were not impaired in epileptic mice
      of both genders. However, female mice, independent of epilepsy, performed the
      beam walk and rotarod tasks better than their male counterparts. We also found
      that only male epileptic mice displayed disturbed behavior in the forced swim
      test, but the mice of both genders displayed anhedonia-like behavior in the taste
      preference test. Lastly, we found that the extent of hilar cell loss is similar
      in both genders. In summary, both genders can be successfully employed to study
      behavioral comorbidities of TLE; however, taking the potential gender differences
      into account may help choose the more appropriated gender for a given task, which
      may be of value for the minimization of the number of animals used during the
      experiments. 

PMID- 25749199
TI  - Emergence of a pandrug-resistant VIM-1-producing Providencia stuartii clonal
      strain causing an outbreak in a Greek intensive care unit.
AB  - Here we describe an outbreak caused by a pandrug-resistant Providencia stuartii
      strain involving 15 critically ill patients in a Greek intensive care unit (ICU)
      during September-November 2011. All isolates harboured the blaVIM-1 gene and a
      class 1 integron structure of 1913 bp as well as blaSHV-5 and blaTEM-1. Pulsed
      field gel electrophoresis (PFGE) demonstrated that isolates from all 15 patients
      belonged to a single P. stuartii clonal type. As all of the infected patients
      were hospitalised during overlapping time periods, horizontal intra-ICU
      transmission was considered as the main route for the dissemination of the
      outbreak strain. The outbreak ended following reinforcement of infection control
      measures, including implementation of additional barrier precautions for infected
      patients. 

PMID- 25749200
TI  - Subtleties in practical application of prolonged infusion of beta-lactam
      antibiotics.
AB  - Prolonged infusion (PI) of beta-lactam antibiotics is increasingly used in order
      to optimise antibiotic exposure in critically ill patients. Physicians are often
      not aware of a number of subtleties that may jeopardise the treatment. In this
      clinically based paper, we stress pragmatic issues, such as the importance of a
      loading dose before PI, and discuss a number of important practicalities that are
      mandatory to benefit from the pharmacokinetic advantages of prolonged beta-lactam
      antibiotic administration. 

PMID- 25749201
TI  - The Birmingham Burn Centre archive: A photographic history of post-war burn care
      in the United Kingdom.
AB  - The Medical Research Council Burns and Industrial Injuries Unit at the Birmingham
      Accident Hospital pioneered civilian burn care and research in the United Kingdom
      during the post-war years. A photographic archive has been discovered that
      documents this period from 1945 to 1975. The aim of this project was to sort,
      digitize and archive the images in a secure format for future reference. The
      photographs detail the management of burns patients, from injury causation and
      surgical intervention, to nursing care, rehabilitation and long-term follow-up. A
      total of 2650 images files were collected from over 600 patients. Many novel
      surgical, nursing, dressing and rehabilitation strategies are documented and
      discussed. We have chosen to report part of the archive under the sections of (1)
      aseptic and antimicrobial burn care; (2) burn excision and wound closure; (3)
      rehabilitation, reconstruction and long-term outcomes; (4) accident prevention;
      and (5) response to a major burns incident. The Birmingham collection gives us a
      valuable insight into the approach to civilian burn care in the post-war years,
      and we present a case from the archive to the modern day, the longest clinical
      photographic follow-up to date. 

PMID- 25749203
TI  - Human papillomavirus and Epstein-Barr virus associated conditions of the oral
      mucosa.
AB  - Human papillomavirus (HPV) and Epstein-Barr virus (EBV) infections of the oral
      mucosa may present as both benign and malignant conditions. Squamous papilloma,
      verruca vulgaris, and condyloma acuminatum are benign, HPV-associated growths
      treated with simple excision while multifocal epithelial hyperplasia (Heck
      disease) usually occurs in children and adolescents and resolves over time. HPV
      associated oral dysplasia is uncommon and HPV-carcinoma comprises 6% of oral
      squamous cell carcinomas. EBV is responsible for oral hairy leukoplakia, a benign
      condition seen in immunocompromised patients, while the EBV-associated
      mucocutaneous ulcer is a recently-described, indolent condition associated with
      an atypical lymphoid proliferation seen immunocompromised patients as well as
      older adults, the latter likely because of immunosenescence. Awareness of these
      conditions is important for the practicing pathologist because some of these
      conditions may represent the first sign of underlying immunocompromise. 

PMID- 25749202
TI  - Role of dendritic cell subsets in immunity and their contribution to
      noninfectious uveitis.
AB  - Dendritic cells (DCs) are a heterogeneous population. Murine DCs consist of
      conventional DCs (cDCs) and plasmacytoid DCs (pDCs). In humans, the analogous
      populations are myeloid DCs (mDCs) and pDCs. Though distinct in phenotypes and
      functions, studies have shown that these DC subsets may interact or "crosstalk"
      during immune responses. For example, cDCs may facilitate pDC maturation, and
      pDCs may enhance antigen presentation of cDCs in certain pathogenic conditions or
      even take on a cDC phenotype themselves. The role of DCs in noninfectious uveitis
      has been studied primarily in the experimental autoimmune uveitis mouse model and
      to a more limited extent in patients. Recent evidence shows that the number,
      phenotype, and function of DC subsets are altered in this disease. We provide an
      overview of selected recent developments of pDCs and cDCs/mDCs, with special
      attention to their interaction and the dual roles of DC subsets in noninfectious
      uveitis. 

PMID- 25749204
TI  - Renal neoplasia: From morphologic to molecular diagnosis.

PMID- 25749205
TI  - Predictive value of immunohistochemistry in pre-malignant lesions of the
      gastrointestinal tract.
AB  - Immunohistochemistry can be an important adjunct to histopathology for the
      diagnosis of pre-malignant lesions of the gastrointestinal tract and in patient
      risk stratification. The purpose of this review is to provide information and
      guidance on the usefulness of immunohistochemical markers that facilitate the
      diagnosis of dysplasia and help to predict risk for the development of carcinoma
      in pre-malignant lesions of the gastrointestinal tract. Particular emphasis is
      given to the role of immunohistochemistry in the assessment of epithelial
      dysplasia in the setting of Barrett's esophagus and inflammatory bowel disease;
      supplementary immunohistochemistry for subtyping adenomas of the stomach and
      ampulla and serrated polyps of the colon and rectum; and ancillary markers of
      squamous neoplasia of the anal canal. 

PMID- 25749195
TI  - Evasion of anti-growth signaling: A key step in tumorigenesis and potential
      target for treatment and prophylaxis by natural compounds.
AB  - The evasion of anti-growth signaling is an important characteristic of cancer
      cells. In order to continue to proliferate, cancer cells must somehow uncouple
      themselves from the many signals that exist to slow down cell growth. Here, we
      define the anti-growth signaling process, and review several important pathways
      involved in growth signaling: p53, phosphatase and tensin homolog (PTEN),
      retinoblastoma protein (Rb), Hippo, growth differentiation factor 15 (GDF15), AT
      rich interactive domain 1A (ARID1A), Notch, insulin-like growth factor (IGF), and
      Kruppel-like factor 5 (KLF5) pathways. Aberrations in these processes in cancer
      cells involve mutations and thus the suppression of genes that prevent growth, as
      well as mutation and activation of genes involved in driving cell growth. Using
      these pathways as examples, we prioritize molecular targets that might be
      leveraged to promote anti-growth signaling in cancer cells. Interestingly,
      naturally occurring phytochemicals found in human diets (either singly or as
      mixtures) may promote anti-growth signaling, and do so without the potentially
      adverse effects associated with synthetic chemicals. We review examples of
      naturally occurring phytochemicals that may be applied to prevent cancer by
      antagonizing growth signaling, and propose one phytochemical for each pathway.
      These are: epigallocatechin-3-gallate (EGCG) for the Rb pathway, luteolin for
      p53, curcumin for PTEN, porphyrins for Hippo, genistein for GDF15, resveratrol
      for ARID1A, withaferin A for Notch and diguelin for the IGF1-receptor pathway.
      The coordination of anti-growth signaling and natural compound studies will
      provide insight into the future application of these compounds in the clinical
      setting. 

PMID- 25749206
TI  - Salient characteristics of youth with type 1 diabetes initiating continuous
      glucose monitoring.
AB  - OBJECTIVE: Consistent continuous glucose monitoring (CGM) use is a challenge in
      youth with type 1 diabetes. This study aimed to investigate patient and family
      behavioral and clinical characteristics associated with interest in implementing
      CGM. RESEARCH DESIGN AND METHODS: In a cross-sectional study, we compared 120
      youth interested in starting CGM (the CGM group) with a general sample of 238
      youth with type 1 diabetes (the Standard group). Youth and their parents
      completed validated surveys assessing adherence to diabetes management, diabetes
      specific family conflict, parent involvement in diabetes management, and youth
      quality of life. Demographic and clinical data were obtained from chart review
      and interview. RESULTS: Youth participants had a mean age of 13.0+/-2.8 years,
      diabetes duration of 6.3+/-3.4 years, and hemoglobin A1c (HbA1c) level of 8.2+/
      1.0% (66+/-11 mmol/mol). Youth in the CGM group performed more frequent blood
      glucose monitoring, had lower HbA1c levels, and were more likely to be treated by
      continuous subcutaneous insulin infusion (CSII) and to be living in two-parent
      homes than youth in the Standard group. Compared with the Standard group, youth
      interested in wearing a CGM device and their parents reported greater adherence
      to diabetes management, less diabetes-specific family conflict, and higher youth
      quality of life. No differences were found between groups with respect to parent
      involvement in diabetes management by both youth and parent reports. CONCLUSIONS:
      In efforts to enhance CGM uptake, it is important to address factors such as
      blood glucose monitoring frequency, CSII use, adherence, and diabetes-specific
      family conflict when considering youth with type 1 diabetes for CGM
      implementation.

PMID- 25749208
TI  - D-beta-hydroxybutyrate: an anti-aging ketone body.

PMID- 25749209
TI  - Rituximab by subcutaneous route.
AB  - Rituximab has become a keystone of the treatment of B-cell lymphoproliferation.
      The standard administration route is intravenous infusion with risks of infusion
      related reactions. In order to make administration easier, increase convenience
      for the patient and improve cost effectiveness, a subcutaneous (sc.) form has
      recently been developed. Early phase clinical studies in patients with follicular
      lymphoma have shown that a fixed dose of 1400 mg by sc. route yielded at least
      non-inferior pharmacokinetics that are at least as good as those of intravenous
      rituximab, as measured by Ctrough levels. The safety profile was also comparable.
      Preliminary analyses of clinical efficacy showed at least non-inferior response
      rates. Although additional information is required, these results suggest that
      sc. rituximab may become a useful option for treating patients with B-cell non
      Hodgkin's lymphoma. 

PMID- 25749207
TI  - Dual effects of collagenase-3 on melanoma: metastasis promotion and disruption of
      vasculogenic mimicry.
AB  - Vasculogenic mimicry (VM) is a functional microcirculation formed by tumor cells.
      Matrix metalloproteinases (MMPs), especially MMP-2 and MMP-9, promote VM
      formation. Another specific MMP, collagenase-3 (MMP-13), has broad substrate
      specificity and potentially affects tumor metastasis and invasion. Here we found
      that MMP-13 was associated with metastasis and poor survival in 79 patients with
      melanoma. MMP-13 expression was inversely correlated with VM. These results were
      confirmed in human and mouse melanoma cell lines. We found that MMP-13 cleaves
      laminin-5 (Ln-5) into small fragments to accelerate tumor metastasis. Degradation
      of Ln-5 and VE-cadherin by MMP-13 inhibited VM formation. In conclusion, MMP-13
      has a dual effect in melanoma, as it promotes invasion and metastasis but
      disrupts VM formation. 

PMID- 25749210
TI  - Conflicts of interest.

PMID- 25749211
TI  - Sentinel lymph node biopsy for melanoma: is there a correlation of preoperative
      lymphatic mapping with sentinel lymph nodes harvested?
AB  - BACKGROUND: Nodal status is the most significant prognostic factor in melanoma.
      No study has examined the relationship between lymphoscintigraphy, gamma probe
      counts, harvested nodes, and nodal status. METHODS: Two-hundred sixty two
      patients were identified who underwent sentinel lymph node biopsy for melanoma
      between 2001 and 2010. Clinicopathologic and treatment information was collected.
      The number of lymph nodes and basins demonstrated on lymphoscintigraphy was
      compared to those at surgery. gamma Probe counts were compared. RESULTS: Median
      age was 54.5 years (range, 18-90 years) with 52.3% male. Average Breslow depth
      was 2.0 (1.9) mm; 99.6% of lymphoscintigraphy studies identified at least 1
      basin, 80% showed only 1 (range, 0-4). Lymphoscintigraphy identified on average
      1.5 (0.9) sentinel nodes and 31% with secondary node. Surgery excised on average
      2.6 (1.4) nodes involving 1.2 (0.5) basins; 17.6% had a positive sentinel lymph
      node. There was no difference in the sum or average of gamma counts between
      positive and negative sentinel lymph node groups (P = 0.2, P = 0.5). When
      comparing lymphoscintigraphy and surgical excision, the correlation of lymphatic
      basins was r = 0.67 and of lymph node numbers was r = 0.33. CONCLUSIONS:
      Lymphoscintigraphy should be used to identify the proper lymphatic basins for a
      sentinel node procedure, however, the removal of nodes must continue until the
      background count is less than 10%. The correlation of lymph node number
      identified on lymphoscintigraphy to surgical excision is weak. gamma Probe counts
      cannot be used to differentiate positive from negative nodes and the positive
      lymph node is not always the hottest node.

PMID- 25749212
TI  - Reconstruction of the dynamic velopharyngeal function by combined radial forearm
      palmaris longus tenocutaneous free flap, and superiorly based pharyngeal flap in
      postoncologic total palatal defect.
AB  - We attempted to reconstruct dynamic palatal function using a radial forearm
      palmaris longus tenocutaneous free flap in conjunction with a pharyngeal flap for
      a postoncologic total-palate defect in a 67-year-old male patient. This
      reconstruction involved 3 important tasks, namely, separating the oral and nasal
      cavities, preserving the velopharyngeal space to avoid sleep apnea, and
      maintaining velopharyngeal closure to avoid nasal regurgitation during
      swallowing. In our technique, the radial forearm flap separates the oral and
      nasal cavities with an open rhinopharyngeal space, and a superiorly based
      pharyngeal flap, which is sutured to the posterior end of the forearm flap,
      limits the rhinopharyngeal space, and forms the bilateral velopharyngeal port.
      Furthermore, the palmaris longus tendon, which is attached to the forearm flap,
      is secured to the superior constrictor muscle to create a horizontal muscle
      sling. Contraction of the superior constrictor muscle leads to shrinkage of the
      sling, resulting in velopharyngeal closure. Swallowing therapy was started 4
      weeks after the surgery. The patient could resume oral intake without any
      difficulties 6 months after the surgery. Speech intelligibility changed from
      severe to minimal hypernasality. 

PMID- 25749213
TI  - Conservative management of partial extensor tendon lacerations greater than half
      the width of the tendon in manual workers.
AB  - Conservative management (without suturing or splints) of partial extensor tendon
      lacerations greater than half the width of the tendon has not been previously
      investigated. In this prospective study, a total of 45 injured tendons (with
      lacerations involving 55%-90% of the width of the tendon) in 39 patients were
      treated conservatively. Injury zones I, III, and V of the fingers; and zones I
      and III of the thumb were excluded. Immediate non-resistive active mobilization
      was initiated and continued for 4 weeks, followed by resistive exercises.
      Patients were allowed to go back to work after 6 weeks. There were no cases of
      ruptures, triggering, infection, or complex regional pain syndrome. At final
      follow-up (8-9 months after injury), all patients obtained full range of motion
      with no extension lags. All patients were able to go back to normal duties. We
      conclude that early active motion without the use of splints or sutures in major
      extensor tendon lacerations in zones II, IV, VI-VIII of the fingers; and zones
      II, IV, and V of the thumb is safe. 

PMID- 25749214
TI  - Dosimetric parameters predict short-term quality-of-life outcomes for patients
      receiving stereotactic body radiation therapy for prostate cancer.
AB  - PURPOSE: Stereotactic body radiation therapy (SBRT) is a treatment option for
      patients with localized prostate cancer, with reported clinical and health
      related quality-of-life (QOL) outcomes comparable to standard fractionation
      radiation therapy. The goal of this study was to evaluate correlations between
      short-term QOL outcomes and dosimetric parameters to guide future prostate SBRT
      planning. METHODS AND MATERIALS: From 2010 to 2013, QOL data were prospectively
      collected from 75 patients enrolled in a prostate SBRT clinical trial. A
      comparison was made between Expanded Prostate Cancer Index Composite scores for
      patients with the top 25th percentile versus the bottom 75th percentile of the
      following dose-volume histogram parameters: planning target volume V100; bladder
      V50 and V100; and rectum V50, V80, V90, and V100. A linear mixed-effect model was
      used to estimate the difference between the 2 strata for each parameter. RESULTS:
      Median follow-up was 12 months. Patients with planning target volume V100 volumes
      >120 cm(3) had the worst reduction in urinary QOL. Urinary QOL was also decreased
      significantly in patients with bladder V100 volumes >5.5 cm(3). Bowel QOL was
      decreased significantly in patients with rectal V90 and V100 volumes >4.2 and
      >1.5 cm(3), respectively. CONCLUSIONS: Patients with large prostate size or large
      volumes of rectum and bladder that receive >=90% of the prescribed radiation dose
      are more susceptible to short-term QOL decrements after prostate SBRT. These
      volumes should be minimized to maximize recovery to baseline QOL after prostate
      SBRT.

PMID- 25749215
TI  - Dosimetric feasibility of magnetic resonance imaging-guided tri-cobalt 60
      preoperative intensity modulated radiation therapy for soft tissue sarcomas of
      the extremity.
AB  - PURPOSE: The purpose of this study was to investigate the dosimetric differences
      of delivering preoperative intensity modulated radiation therapy (IMRT) to
      patients with soft tissue sarcomas of the extremity (ESTS) with a teletherapy
      system equipped with 3 rotating (60)Co sources and a built-in magnetic resonance
      imaging and with standard linear accelerator (LINAC)-based IMRT. METHODS AND
      MATERIALS: The primary study population consisted of 9 patients treated with
      preoperative radiation for ESTS between 2008 and 2014 with LINAC-based static
      field IMRT. LINAC plans were designed to deliver 50 Gy in 25 fractions to 95% of
      the planning target volume (PTV). Tri-(60)Co system IMRT plans were designed with
      ViewRay system software. RESULTS: Tri-(60)Co-based IMRT plans achieved equivalent
      target coverage and dosimetry for organs at risk (long bone, skin, and skin
      corridor) compared with LINAC-based IMRT plans. The maximum and minimum PTV
      doses, heterogeneity indices, and ratio of the dose to 50% of the volume were
      equivalent for both planning systems. One LINAC plan violated the maximum bone
      dose constraint, whereas none of the tri-(60)Co plans did. CONCLUSIONS: Using a
      tri-(60)Co system, we were able to achieve equivalent dosimetry to the PTV and
      organs at risk for patients with ESTS compared with LINAC-based IMRT plans. The
      tri-(60)Co system may be advantageous over current treatment platforms by
      allowing PTV reduction and by elimination of the additional radiation dose
      associated with daily image guidance, but this needs to be evaluated
      prospectively.

PMID- 25749216
TI  - Global harmonisation in vaccine price.

PMID- 25749217
TI  - PANGEA-HIV: phylogenetics for generalised epidemics in Africa.

PMID- 25749218
TI  - Combination HIV prevention and the battle of the sexes.

PMID- 25749219
TI  - Corrections. The expanding role of co-trimoxazole in developing countries.

PMID- 25749220
TI  - Corrections. Emergency Ebola response: a new approach to the rapid design and
      development of vaccines against emerging diseases.

PMID- 25749221
TI  - Corrections. Hospital organisation, management, and structure for prevention of
      health-care-associated infection: a systematic review and expert consensus.

PMID- 25749222
TI  - Corrections. Travel-associated infection presenting in Europe (2008-12): an
      analysis of EuroTravNet longitudinal, surveillance data, and evaluation of the
      effect of the pre-travel consultation.

PMID- 25749223
TI  - Corrections. Comparative effectiveness of high-dose versus standard-dose
      influenza vaccines in US residents aged 65 years and older from 2012 to 2013
      using Medicare data: a retrospective cohort analysis.

PMID- 25749224
TI  - Combined antiparasitic treatment for neurocysticercosis.

PMID- 25749225
TI  - Combined antiparasitic treatment for neurocysticercosis.

PMID- 25749226
TI  - Combined antiparasitic treatment for neurocysticercosis.

PMID- 25749227
TI  - Combined antiparasitic treatment for neurocysticercosis - Authors' reply.

PMID- 25749228
TI  - Influenza vaccine for Hajj and Umrah pilgrims.

PMID- 25749229
TI  - HEV-associated cryoglobulinaemia and extrahepatic manifestations of hepatitis E.

PMID- 25749230
TI  - New CDC guidelines recommend circumcision to cut HIV risk.

PMID- 25749231
TI  - New antibiotic development hailed as game changing.

PMID- 25749234
TI  - BT Slingsby: driving forward innovation in global health.

PMID- 25749237
TI  - Primary iliopsoas abscess in a diabetic patient.

PMID- 25749238
TI  - The Health Benefits of Selected Culinary Herbs and Spices Found in the
      Traditional Mediterranean Diet.
AB  - The Mediterranean diet is considered one of the healthiest diets in the world.
      This is often attributed to low saturated fat consumption, moderate wine
      consumption, and high vegetable consumption. However, herbs and spices associated
      with these diets may also play an important role in the quality of this diet.
      This review summarizes the most recent research regarding the anti-diabetic, anti
      inflammatory, anti-hyperlipidemic and anti-hypertensive properties of this
      collection of culinary species. Additionally, this review briefly summarizes
      studies performed on lesser known herbs from around the world, with the goal of
      identifying new culinary species that may be useful in the treatment or
      prevention of diseases. 

PMID- 25749239
TI  - Correction: Pyridine synthesis from oximes and alkynes via rhodium(III)
      catalysis: Cp* and Cp(t) provide complementary selectivity.

PMID- 25749240
TI  - Audio-vocal responses of vocal fundamental frequency and formant during sustained
      vowel vocalizations in different noises.
AB  - Sustained vocalizations of vowels [a], [i], and syllable [me] were collected in
      twenty normal-hearing individuals. On vocalizations, five conditions of different
      audio-vocal feedback were introduced separately to the speakers including no
      masking, wearing supra-aural headphones only, speech-noise masking, high-pass
      noise masking, and broad-band-noise masking. Power spectral analysis of vocal
      fundamental frequency (F0) was used to evaluate the modulations of F0 and linear
      predictive-coding was used to acquire first two formants. The results showed that
      while the formant frequencies were not significantly shifted, low-frequency
      modulations (<3 Hz) of F0 significantly increased with reduced audio-vocal
      feedback across speech sounds and were significantly correlated with auditory
      awareness of speakers' own voices. For sustained speech production, the motor
      speech controls on F0 may depend on a feedback mechanism while articulation
      should rely more on a feedforward mechanism. Power spectral analysis of F0 might
      be applied to evaluate audio-vocal control for various hearing and neurological
      disorders in the future. 

PMID- 25749241
TI  - Author's response to "Venous thromboembolism in heart transplantation. Should we
      consider genetic predisposition?".

PMID- 25749242
TI  - Percutaneous thoracic paravertebral block reduces refractory ventricular
      tachyarrhythmias after left ventricular assist device implantation.

PMID- 25749244
TI  - Kuehne LK, Reiber H, Bechter K, Hagberg L, Fuchs D., Cerebrospinal fluid
      neopterin is brain-derived and not associated with blood-CSF barrier dysfunction
      in non-inflammatory affective and schizophrenic spectrum disorders. Journal of
      Psychiatric Research, Volume 47, Issue 10, October 2013, pages 1417-1422.

PMID- 25749243
TI  - Irisin - a myth rather than an exercise-inducible myokine.
AB  - The myokine irisin is supposed to be cleaved from a transmembrane precursor,
      FNDC5 (fibronectin type III domain containing 5), and to mediate beneficial
      effects of exercise on human metabolism. However, evidence for irisin circulating
      in blood is largely based on commercial ELISA kits which are based on polyclonal
      antibodies (pAbs) not previously tested for cross-reacting serum proteins. We
      have analyzed four commercial pAbs by Western blotting, which revealed prominent
      cross-reactivity with non-specific proteins in human and animal sera. Using
      recombinant glycosylated and non-glycosylated irisin as positive controls, we
      found no immune-reactive bands of the expected size in any biological samples. A
      FNDC5 signature was identified at ~20 kDa by mass spectrometry in human serum but
      was not detected by the commercial pAbs tested. Our results call into question
      all previous data obtained with commercial ELISA kits for irisin, and provide
      evidence against a physiological role for irisin in humans and other species. 

PMID- 25749245
TI  - Soft tissue surgery: a rapidly evolving field.

PMID- 25749246
TI  - Inactivated polio vaccination using a microneedle patch is immunogenic in the
      rhesus macaque.
AB  - The phased replacement of oral polio vaccine (OPV) with inactivated polio vaccine
      (IPV) is expected to significantly complicate mass vaccination campaigns, which
      are an important component of the global polio eradication endgame strategy. To
      simplify mass vaccination with IPV, we developed microneedle patches that are
      easy to administer, have a small package size, generate no sharps waste and are
      inexpensive to manufacture. When administered to rhesus macaques, neutralizing
      antibody titers were equivalent among monkeys vaccinated using microneedle
      patches and conventional intramuscular injection for IPV types 1 and 2. Serologic
      response to IPV type 3 vaccination was weaker after microneedle patch vaccination
      compared to intramuscular injection; however, we suspect the administered type 3
      dose was lower due to a flawed pre-production IPV type 3 analytical method. IPV
      vaccination using microneedle patches was well tolerated by the monkeys. We
      conclude that IPV vaccination using a microneedle patch is immunogenic in rhesus
      macaques and may offer a simpler method of IPV vaccination of people to
      facilitate polio eradication. 

PMID- 25749247
TI  - Relationship between Guillain-Barre syndrome, influenza-related hospitalizations,
      and influenza vaccine coverage.
AB  - Some studies reported an increased risk of Guillain-Barre syndrome (GBS) within
      six weeks of influenza vaccination. It has also been suggested that this finding
      could have been confounded by influenza illnesses. We explored the complex
      relationship between influenza illness, influenza vaccination, and GBS, from an
      ecologic perspective using nationally representative data. We also studied
      seasonal patterns for GBS hospitalizations. Monthly hospitalization data (2000
      2009) for GBS, and pneumonia and influenza (P&I) in the Nationwide Inpatient
      Sample were included. Seasonal influenza vaccination coverage for 2004-2005
      through the 2008-2009 influenza seasons (August-May) was estimated from the
      National Health Interview Survey data. GBS seasonality was determined using
      Poisson regression. GBS and P&I temporal clusters were identified using scan
      statistics. The association between P&I and GBS hospitalizations in the same
      month (concurrent) or in the following month (lagged) were determined using
      negative binomial regression. Vaccine coverage increased over the years (from
      19.7% during 2004-2005 to 35.5% during 2008-2009 season) but GBS hospitalization
      did not follow a similar pattern. Overall, a significant correlation between
      monthly P&I and GBS hospitalizations was observed (Spearman's correlation
      coefficient=0.7016, p<0.0001). A significant (p=0.001) cluster of P&I
      hospitalizations during December 2004-March 2005 overlapped a significant
      (p=0.001) cluster of GBS hospitalizations during January 2005-February 2005.
      After accounting for effects of monthly vaccine coverage and age, P&I
      hospitalization was significantly associated (p<0.0001) with GBS hospitalization
      in the concurrent month but not with GBS hospitalization in the following month.
      Monthly vaccine coverage was not associated with GBS hospitalization in adjusted
      models (both concurrent and lagged). GBS hospitalizations demonstrated a seasonal
      pattern with winter months having higher rates compared to the month of June. P&I
      hospitalization rates were significantly correlated with hospitalization rates
      for GBS. Vaccine coverage did not significantly affect the rates of GBS
      hospitalization at the population level. 

PMID- 25749249
TI  - WHO consultation on clinical evaluation of vaccines, 17-18 July 2014, WHO
      Headquarters, Geneva, Switzerland.
AB  - A World Health Organization (WHO) consultation on guidelines for National
      Regulatory Authorities (NRAs) and vaccine manufacturers on clinical evaluation of
      vaccines was held from 17 to 18 July 2014, to review key scientific challenges
      that regulators have been facing since the establishment of the WHO Guidelines on
      Clinical Evaluation of Vaccines. The guidelines, adopted by the WHO Expert
      Committee on Biological Standardization (ECBS) in 2001, have served as the basis
      for setting or updating national requirements for the evaluation and licensing of
      a broad range of vaccines as well as for WHO vaccine prequalification. Regulators
      from Australia, Brazil, China, Canada, Germany, India, Republic of Korea, South
      Africa, United States of America and the United Kingdom were represented. The
      International Federation for Pharmaceutical Manufacturers' Association (IFPMA)
      and the Developing Country Vaccine Manufacturers' Network (DCVMN) provided
      industry representation. The consultation concluded that the guidelines should be
      revised to address issues that were raised in the context of vaccines that were
      the subject of clinical development in the past decade. Although the current
      guidelines have served well over time, it was recognized that an update would
      further increase their utility and would help regulators, manufacturers, vaccine
      developers and academia to respond to the challenging questions regarding the
      safety, immunogenicity, efficacy and effectiveness of vaccines intended for
      global use. A summary of the main outcomes of the consultation and proposals for
      the next steps regarding the guidelines and beyond are provided in this report. 

PMID- 25749248
TI  - Vaccines, our shared responsibility.
AB  - The Developing Countries Vaccine Manufacturers' Network (DCVMN) held its
      fifteenth annual meeting from October 27-29, 2014, New Delhi, India. The DCVMN,
      together with the co-organizing institution Panacea Biotec, welcomed over 240
      delegates representing high-profile governmental and nongovernmental global
      health organizations from 36 countries. Over the three-day meeting, attendees
      exchanged information about their efforts to achieve their shared goal of
      preventing death and disability from known and emerging infectious diseases.
      Special praise was extended to all stakeholders involved in the success of polio
      eradication in South East Asia and highlighted challenges in vaccine supply for
      measles-rubella immunization over the coming decades. Innovative vaccines and
      vaccine delivery technologies indicated creative solutions for achieving global
      immunization goals. Discussions were focused on three major themes including
      regulatory challenges for developing countries that may be overcome with better
      communication; global collaborations and partnerships for leveraging investments
      and enable uninterrupted supply of affordable and suitable vaccines; and leading
      innovation in vaccines difficult to develop, such as dengue, Chikungunya, typhoid
      conjugated and EV71, and needle-free technologies that may speed up vaccine
      delivery. Moving further into the Decade of Vaccines, participants renewed their
      commitment to shared responsibility toward a world free of vaccine-preventable
      diseases. 

PMID- 25749250
TI  - Underdeveloped or underreported? Coverage of pretesting practices and
      recommendations for design of text message-based health behavior change
      interventions.
AB  - Text messaging interventions for health are becoming increasingly popular, but it
      is unclear how rigorously such interventions are developed and pretested before
      being implemented. Pretesting is important to the development of successful
      health communication interventions. This study reviewed the literature published
      on text messaging health behavior change interventions and examined pretesting
      practices. Results showed that pretesting is rarely mentioned in articles,
      although it is not clear as to why. Six articles mentioned pretesting practices
      conducted for their mobile intervention, and three articles were written
      specifically on the pretesting of an intervention. Most pretesting used
      qualitative methods. Recommendations are provided on pretesting best practices
      and pretesting reporting to help other researchers in the field of mobile health.

PMID- 25749251
TI  - Statement of removal.
AB  - Article title: Phosphorylation of the p52 NF-kB subunit. Authors: Benjamin Barre
      and Neil D Perkins. Journal: Cell Cycle. Bibliometrics: Volume 9, Issue 24, 2010
      pages 4774-4775. DOI: 10.4161/cc.9.24.14246.Publisher: Taylor & Francis. We, the
      Editor and Publisher of Cell Cycle, have removed the following accepted
      manuscript that was posted online 15 December 2010: Benjamin Barre and Neil D
      Perkins, "P Phosphorylation of the p52 NF-kB subunit" DOI: 10.4161/cc.9.24.14246.
      Cell Cycle. This article has been removed due to a number of issues with the
      original 2010 Cell Cycle article entitled "Regulation of activity and function of
      the p52 NF-kB subunit following DNA damage" (Barre B., et al. Cell Cycle 2010;
      9:4795-804; PMID: 21131783; http://dx.doi.org/10.4161/cc.9.24.14245). This
      article is a commentary on the retracted paper detailed above. Consequently, in
      our opinion the integrity of the manuscript has been compromised, and there is no
      option but to retract the paper. We note we received, peer-reviewed, accepted,
      and published the article in good faith. The retracted article will remain online
      to maintain the scholarly record, but it will be digitally watermarked on each
      page as RETRACTED.

PMID- 25749253
TI  - Mental health service utilization in sub-Saharan Africa: is public mental health
      literacy the problem? Setting the perspectives right.
AB  - The severely constrained resources for mental health service in less-developed
      regions like sub-Saharan Africa underscore the need for good public mental health
      literacy as a potential additional mental health resource. Several studies
      examining the level of public knowledge about the nature and dynamics of mental
      illness in sub-Saharan Africa in the last decade had concluded that such
      knowledge was poor and had called for further public enlightenment. What was
      thought to be mental health 'ignorance' has also been blamed for poor mainstream
      service utilization. These views however assume that non-alignment of the views
      of community dwellers in sub-Saharan Africa with the biomedical understanding of
      mental illness connotes 'ignorance', and that correcting such 'ignorance' will
      translate to improvements in service utilization. Within the framework of
      contemporary thinking in mental health literacy, this paper argues that such
      assumptions are not culturally nuanced and may have overrated the usefulness of
      de-contextualized public engagement in enhancing mental health service
      utilization in the region. The paper concludes with a discourse on how to
      contextualize public mental health enlightenment in the region and the wider
      policy initiatives that can improve mental health service utilization. 

PMID- 25749254
TI  - Fluid Dynamics and Biofilm Removal Generated by Syringe-delivered and 2
      Ultrasonic-assisted Irrigation Methods: A Novel Experimental Approach.
AB  - INTRODUCTION: Thorough understanding of fluid dynamics in root canal irrigation
      and corresponding antibiofilm capacity will support improved disinfection
      strategies. This study aimed to develop a standardized, simulated root canal
      model that allows real-time analysis of fluid/irrigation dynamics and its
      correlation with biofilm elimination. METHODS: A maxillary incisor with an
      instrumented root canal was imaged with micro-computed tomography. The canal
      volume was reconstructed in 3 dimensions and replicated in soft lithography-based
      models microfabricated from polyethylene glycol-modified polydimethylsiloxane.
      Canals were irrigated by using a syringe (SI) and 2 ultrasonic-assisted methods,
      intermittent (IUAI) and continuous (CUAI). Real-time fluid movement within the
      apical 3 mm of canals was imaged by using microparticle image velocimetry. In
      similar models, canals were inoculated with Enterococcus faecalis to grow 3-week
      old biofilms. Biofilm reduction by irrigation with SI, CUAI, and IUAI was
      assessed by using a crystal violet assay and compared with an untreated control.
      RESULTS: SI generated higher velocity and shear stress in the apical 1-2 mm than
      0-1 and 2-3 mm. IUAI generated consistently low shear stress in the apical 3 mm.
      CUAI generated consistently high levels of velocity and shear stress; it was the
      highest of the groups in the apical 0-1 and 2-3 mm. Biofilm was significantly
      reduced compared with the control only by CUAI (two-sample permutation test, P =
      .005). CONCLUSIONS: CUAI exhibited the highest mechanical effects of fluid flow
      in the apical 3 mm, which correlated with significant biofilm reduction. The soft
      lithography-based models provided a novel model/method for study of correlations
      between fluid dynamics and the antibiofilm capacity of root canal irrigation
      methods.

PMID- 25749255
TI  - Histologic examination of teeth with necrotic pulps and periapical lesions
      treated with 2 scaffolds: an animal investigation.
AB  - INTRODUCTION: Traditional pulp regeneration procedures that use a blood clot as a
      scaffold have produced histologic evidence of bone, cementum, and connective
      tissue growth within the root. Platelet-rich plasma (PRP) is a bioactive scaffold
      containing growth factors that enhance wound healing. AIM: The aim of this study
      was to histologically compare the tissues generated when PRP or a blood clot is
      placed into teeth with preexisting necrotic pulps and periapical lesions.
      METHODS: Twenty-four canine teeth from 6 immature ferrets were used. Two ferrets
      served as positive controls. Sixteen experimental canine teeth from 4 ferrets
      were infected, debrided, treated with a triple antibiotic paste, and randomly
      distributed to the following groups: group 1 (blood clot/Gelfoam), group 2 (PRP),
      and group 3 (no scaffold). At 3 months, the ferrets were sacrificed, and the
      tissues were evaluated histologically. Data were analyzed by using the Fisher
      exact test (P < .05). RESULTS: In 3 of 6 teeth in the PRP group, 2 of 6 teeth in
      the blood clot group, and 1 of 4 teeth in the no scaffold group, an ingrowth of
      hard tissues was observed in the apical third of the roots. When using PRP or a
      blood clot as a scaffold, we found significantly more apical narrowing and hard
      tissue deposition in comparison to not using a scaffold (P < .05). CONCLUSIONS:
      The use of PRP or blood clots as scaffolds results in the ingrowth of bone-like,
      cementum-like, and connective tissue in the apical third of the roots at
      inconsistent rates.

PMID- 25749252
TI  - A systems-level interrogation identifies regulators of Drosophila blood cell
      number and survival.
AB  - In multicellular organisms, cell number is typically determined by a balance of
      intracellular signals that positively and negatively regulate cell survival and
      proliferation. Dissecting these signaling networks facilitates the understanding
      of normal development and tumorigenesis. Here, we study signaling by the
      Drosophila PDGF/VEGF Receptor (Pvr) in embryonic blood cells (hemocytes) and in
      the related cell line Kc as a model for the requirement of PDGF/VEGF receptors in
      vertebrate cell survival and proliferation. The system allows the investigation
      of downstream and parallel signaling networks, based on the ability of Pvr to
      activate Ras/Erk, Akt/TOR, and yet-uncharacterized signaling pathway/s, which
      redundantly mediate cell survival and contribute to proliferation. Using Kc
      cells, we performed a genome wide RNAi screen for regulators of cell number in a
      sensitized, Pvr deficient background. We identified the receptor tyrosine kinase
      (RTK) Insulin-like receptor (InR) as a major Pvr Enhancer, and the nuclear
      hormone receptors Ecdysone receptor (EcR) and ultraspiracle (usp), corresponding
      to mammalian Retinoid X Receptor (RXR), as Pvr Suppressors. In vivo analysis in
      the Drosophila embryo revealed a previously unrecognized role for EcR to promote
      apoptotic death of embryonic blood cells, which is balanced with pro-survival
      signaling by Pvr and InR. Phosphoproteomic analysis demonstrates distinct modes
      of cell number regulation by EcR and RTK signaling. We define common
      phosphorylation targets of Pvr and InR that include regulators of cell survival,
      and unique targets responsible for specialized receptor functions. Interestingly,
      our analysis reveals that the selection of phosphorylation targets by signaling
      receptors shows qualitative changes depending on the signaling status of the
      cell, which may have wide-reaching implications for other cell regulatory
      systems. 

PMID- 25749256
TI  - Reducing the vigilance decrement: The effects of perceptual variability.
AB  - The longer we are required to monitor for rare but critical events, the accuracy
      and speed with which we detect such events tend to suffer (the 'vigilance
      decrement') with more difficult tasks yielding larger decrements. Here, we
      present a striking example of a situation in which increasing the difficulty and
      complexity of a novel vigilance task actually decreases the vigilance decrement.
      In a 'Stable' condition participants monitored for the same critical target
      throughout the task, whereas in a 'Variable' condition, participants monitored
      for many possible instantiations of the critical target. Despite the fact that
      the Variable condition was objectively more difficult, the vigilance decrement
      was significantly reduced in response times relative to the Stable condition. We
      discuss these findings in light of 'overload' and 'underload' theories of the
      vigilance decrement and suggest that perceptual variability may provide bottom-up
      support for the maintenance of attentional resource allocation to an external
      task. 

PMID- 25749257
TI  - Clinical relevance of herpes simplex virus viremia in Intensive Care Unit
      patients.
AB  - OBJECTIVES: To determine the clinical relevance of herpes simplex virus (HSV)
      viremia episodes in critically ill adult patients. METHODS: 1556 blood samples
      obtained for HSV PCR analysis in Intensive Care Unit (ICU) patients over 4 years
      were retrospectively analyzed, focusing on the comprehensive analysis of 88 HSV
      viremic patients. RESULTS: HSV DNA was detected in 11.8% of samples from the ICU.
      HSV viral loads remained below 5*10(2) copies/ml in 68.2% of patients and
      exceeded 10(4) copies/ml in 7.9%. Episodes of HSV-viremia correlated with
      immunosuppressed status and mechanical ventilation in 79.5% and 65.9% of
      patients, respectively. Only a subset of patients exhibited HSV-related organ
      damage, including pneumonia and hepatitis (10.2% and 2.3%, respectively). The
      mortality rate in HSV-viremic patients was not significantly increased compared
      to the overall mortality rate in the ICU (27.3% vs. 22.9%, p = 0.33). Only
      patients with high HSV viral loads tended to have a higher, though non
      significant, death rate (57.1%, p = 0.14). CONCLUSIONS: Our results suggest HSV
      viremia is common in ICU patients, potentially favored by immunocompromised
      status and mechanical ventilation. The global impact of HSV-viremia on mortality
      in the ICU was low. Quantifying HSV DNA may help identifying patients at-risk of
      severe HSV-induced symptoms.

PMID- 25749258
TI  - Acute graft-versus-host disease, invasive aspergillosis and Clostridium difficile
      colitis after peripheral blood stem cell transplantation: A complex network of
      causalities and a challenge for prevention.
AB  - Graft-versus-host disease (GVHD) is a known risk factor for invasive
      aspergillosis (IA), but remains poorly studied in relation to Clostridium
      difficile infection (CDI). We report a case of a 58-years-old patient who
      developed an IA within a protected room, CDI and GVHD after allogeneic allogeneic
      peripheral blood stem cell transplantation (PBSCT). Factors associated with this
      complex condition in patients receiving allogeneic PBSCT need to be identified. 

PMID- 25749259
TI  - Multidisciplinary treatment of olfactory neuroblastoma: Patterns of failure and
      management of recurrence.
AB  - PURPOSE: Esthesioneuroblastoma is an uncommon malignancy of the head and neck for
      which there is no defined treatment protocol. The purpose of this study is to
      report our experience with the treatment and patterns of failure of this disease.
      METHODS AND MATERIALS: From 1994 to 2012, 37 previously unreported patients with
      esthesioneuroblastoma were evaluated, and 32 eventually treated for cure at 2
      academic medical centers. All patients were staged with Kadish criteria. The mean
      and median follow-ups were 96.1 and 76.5 months respectively (range 6-240
      months). RESULTS: The Kadish stage was A in 6 patients, B in 13 patients, and C
      in 13 patients. Four patients were initially treated with concurrent chemo
      radiation therapy. Twenty-eight patients were treated with primary surgery. Two
      (2) underwent open medial maxillectomy and 26 underwent craniofacial resection
      (open - 17, endoscopic - 9). Three patients received curative surgical resection
      only. Seven patients failed either within the cranial axis or distantly, 6 of the
      7 are dead of disease, 10-194 months following initial treatment. Six patients
      had isolated neck recurrences, 4/6 were salvaged with neck dissection and
      additional chemo-radiation and remain alive 30-194 months following initial
      treatment. Estimated overall survival rate at 10 years was 78% based on Kadish
      and T stages. CONCLUSION: In this retrospective analysis of 32 patients, Kadish
      stage C and stage T3/T4 tumors were associated with worse outcome. Total
      radiation dose of 60 Gy, margin status, patient age, were not found to have
      significant prognostic value.

PMID- 25749260
TI  - Pharmacists' role in tuberculosis: Prevention, screening, and treatment.

PMID- 25749261
TI  - 30/60/10 Rule of effective performance planning.

PMID- 25749263
TI  - Evaluating health outcomes following a pharmacist-provided comprehensive
      pretravel health clinic in a supermarket pharmacy.
AB  - OBJECTIVES: To evaluate health outcomes and acceptance of pharmacists'
      recommendations of travel health including prevalance of immunizations, sunburn,
      insect-borne diseases, traveler's diarrhea, and altitude sickness, and assess
      patient satisfaction with the pretravel health clinic. DESIGN: Retrospective
      cross-sectional study design. SETTING: Central Virginia, July 2011 to June 2012.
      PARTICIPANTS: Patients 18 years and older who had an appointment with the
      pharmacist for pretravel health. INTERVENTION: Interview/survey administered to
      patients by telephone. MAIN OUTCOME MEASURES: Health outcomes, acceptance rates
      of pharmacist's travel health recommendations, and patient satisfaction. RESULTS:
      Of 356 patients eligible to participate in the study, 103 patients participated,
      30 patients declined, and 223 patients could not be reached by telephone (29%
      response rate). Pharmacists' recommendations for travel immunizations (100%
      acceptance rate for yellow fever and 82% for Typhoid) and nonpharmacologic
      preventive measures (prevention of sunburn, traveler's diarrhea, insect bites,
      and altitude sickness) were well accepted by respondents, and occurrence of these
      adverse events was low. Patients were satisfied overall with the education and
      services that the pharmacist delivered in the pretravel health clinic.
      CONCLUSION: Pharmacists providing services in pretravel health clinics can have
      substantial impact on the health of patients traveling internationally.

PMID- 25749264
TI  - Physician-pharmacist collaborative care model for buprenorphine-maintained opioid
      dependent patients.
AB  - OBJECTIVES: To develop a physician-pharmacist collaborative practice for opioid
      dependent patients designed to increase access to treatment, optimize patient
      care, reduce cost, minimize physician burden, and prevent diversion. SETTING:
      Suburban health department. PRACTICE DESCRIPTION: Physician-pharmacist
      buprenorphine/naloxone maintenance practice. PRACTICE INNOVATION: Traditionally,
      health department buprenorphine/naloxone patients have been referred to community
      physicians at considerable cost with varying outcomes. In this pilot project,
      patients were managed using a drug therapy management model. Intake assessments
      and follow-up appointments were conducted by the pharmacist. The pharmacist
      debriefed with the physician and documented each interaction, allowing for
      efficient assessment completion. The physician appended notes, when applicable,
      and cosigned each patient's record. The pharmacist prevented diversion by
      gathering data from outside providers, pharmacies, and laboratories. RESULTS:
      This health department program improved care by producing structure and expanding
      treatment options. A total of 12 patients completed full intakes with 135 follow
      up appointments equating to an estimated savings of $22,000. The program
      demonstrated a 91% attendance rate, 100% 6-month retention rate, and 73% 12-month
      retention rate. Overall, 127 (98%) urine toxicology screens were positive for
      buprenorphine and 114 (88%) were positive for buprenorphine and negative for
      opioids. CONCLUSION: Physician and pharmacist collaboration optimized care of
      buprenorphine-maintained patients. Data from this pilot were used to develop a
      permanent physician-pharmacist program and to obtain approval for the first state
      approved opioid use disorder drug therapy management protocol.

PMID- 25749265
TI  - Pharmacist provider status legislation: Projections and prospects.
AB  - OBJECTIVE: To compare legislation at the federal level that would recognize
      pharmacists as health care providers under Medicare Part B with similar state
      level efforts in an attempt to identify the strengths and weaknesses of these
      options and forecast outcomes. SUMMARY: The current primary care provider
      shortage poses a significant threat to public health in the United States. The
      effort to achieve federal provider status for pharmacists, currently in the form
      of identical bills introduced in January 2015 into the U.S. House of
      Representatives and the U.S. Senate as the Pharmacy and Medically Underserved
      Areas Enhancement Act (H.R. 592 and S. 314), would amend the Social Security Act
      to recognize pharmacists as health care providers in sections of Medicare Part B
      that specify coverage and reimbursement. This action has budgetary implications
      owing to the compensation that would accrue to pharmacists caring for Medicare
      beneficiaries. Passage of these bills into law could improve public health by
      sustainably increasing access to pharmacists' patient care services in medically
      underserved areas. In this article, the legislation's strengths and weaknesses
      are analyzed. The resulting information may be used to forecast the bills' fate
      as well as plan strategies to help support their success. Comparison of the bills
      with existing, state-level efforts is used as a framework for such policy
      analysis. CONCLUSION: While the current political climate benefits the bills in
      the U.S. Congress, established legislative precedents suggest that parts of H.R.
      592/S. 314, specifically those regarding compensation mechanisms, may require
      negotiated amendment to improve their chances of success.

PMID- 25749266
TI  - Vaccine Update: Recommendation for conjugate pneumococcal and pneumococcal
      polysaccharide vaccines in adults older than 65 years.

PMID- 25749267
TI  - Ledipasvir/sofosbuvir; ombitasvir/paritaprevir/ritonavir/dasabuvir sodium
      monohydrate; and peramivir.

PMID- 25749268
TI  - Transitions of care programs with pharmacists continue to demonstrate benefit.

PMID- 25749270
TI  - Preventing medication errors in transitions of care: A patient case approach.
AB  - OBJECTIVE: To discuss common causes of medication errors occurring upon
      transitions of care and review key interventions that should be implemented to
      ensure effective communication and accurate completion of medication
      reconciliation. DATA SOURCES: MEDLINE (1946 to November 2014) using MeSH terms
      medication errors, medication reconciliation, and nursing homes in addition to
      conventional text words, including transitions of care and medication safety;
      Agency for Healthcare Research and Quality Patient Safety Network using search
      terms transitions of care, medication errors, and medication reconciliation; and
      relevant websites of national organizations pertaining to transitions of care and
      medication reconciliation. STUDY SELECTION: Limited to English-language journals
      with no limitation set on the year of publication for clinical trials, meta
      analyses, and reviews. DATA EXTRACTION: At the authors' discretion, preference
      was given to references focusing on pharmacists' role in transitions of care and
      medication reconciliation. RESULTS: Most medication errors stem from a lack of
      effective communication between health care providers during transitions of care.
      Part of successful communication and correct patient hand-off is completing
      accurate medication reconciliation. A patient case highlights a life-threatening
      medication error that occurred during a transition of care due to ineffective
      communication between a pharmacist and nurse while transferring medication
      information. CONCLUSION: To provide patients with accurate medication
      information, pharmacists should perform medication reconciliation upon
      transitions of care using The Joint Commission's five-step process. Pharmacists
      can conduct numerous interventions to prevent medication errors during
      transitions of care and ensure patient safety. Pharmacists are integral to
      evaluating the appropriateness of medication use, ensuring information is updated
      in the health record, and verbally communicating accurate information to other
      health professionals.

PMID- 25749271
TI  - The vegetative buds of Salix myrsinifolia are responsive to elevated UV-B and
      temperature.
AB  - The predicted rise in temperature and variable changes in ultraviolet-B radiation
      will have marked effects on plant growth and metabolism. Different vegetative
      parts of trees have been studied to detect the impacts of enhanced temperature
      and UV-B, but the effects on buds have rarely been considered. In the present
      study, Salix myrsinifolia clones were subjected to enhanced UV-B and temperature
      over two growing seasons starting from 2009, and measured springtime bud
      development and concentrations of phenolic compounds. In 2010 and 2011 the buds
      under increased temperature were up to 30% longer than those in control plots. On
      the other hand, UV-B combined with elevated temperature significantly decreased
      bud length by 4-5% in 2010. This effect was stronger in males than in females.
      The vegetative buds contained high constitutive amounts of chlorogenic acid
      derivatives, which may explain the weak increase in hyperin and chlorogenic acid
      that are usual UV-B sheltering compounds. The elevated temperature treatment
      significantly increased salicin content (about 18% in males and 22% in females),
      while triandrin concentration decreased by only 50% in females. Our results
      indicate that vegetative bud size is highly affected by seasonal temperature,
      while UV-B induced a weaker and transient effect. 

PMID- 25749272
TI  - The effects of UV radiation during the vegetative period on antioxidant compounds
      and postharvest quality of broccoli (Brassica oleracea L.).
AB  - In this study, the effects of supplementary UV radiation during the vegetative
      period on antioxidant compounds, antioxidant activity and postharvest quality of
      broccoli heads during long term storage was studied. The broccolis were grown
      under three different doses of supplementary UV radiation (2.2, 8.8 and 16.4
      kJ/m(2)/day) in a soilless system in a glasshouse. Harvested broccoli heads were
      stored at 0  degrees C in modified atmosphere packaging for 60 days. The
      supplementary UV radiation (280-315 nm) during the vegetative period
      significantly decreased total carotenoid, the chlorophyll a and chlorophyll b
      content but increased the ascorbic acid, total phenolic and flavonoid contents of
      broccolis. All supplementary UV treatments slightly reduced the antioxidant
      activity of the broccolis, however, no remarkable change was observed between 2.2
      and 8.8 kJ/m(2) radiation levels. The sinigrin and glucotropaeolin contents of
      the broccolis were substantially increased by UV treatments. The prolonged
      storage period resulted in decreased ascorbic acid, total phenolic and flavonoid
      contents, as well as antioxidant activity. Discoloration of the heads, due to
      decreased chlorophyll and carotenoid contents, was also observed with prolonged
      storage duration. Glucosinolates levels showed an increasing tendency till the
      45th day of storage, and then their levels started to decline. The weight loss of
      broccoli heads during storage progressively increased with storage time in all
      treatments. Total soluble solids, solids content and titratable acidity decreased
      continuously during storage. Titratable acidity was not affected by UV radiation
      doses during the storage time whereas soluble solids and solids content (dry
      matter) were significantly affected by UV doses. Supplementary UV radiation
      increased the lightness (L*) and chroma (C*) values of the broccoli heads. Pre
      harvest UV radiation during vegetative period seems to be a promising tool for
      increasing the beneficial health components of broccolis.

PMID- 25749273
TI  - Nanoscale electrostatic control of oxide interfaces.
AB  - We develop a robust and versatile platform to define nanostructures at oxide
      interfaces via patterned top gates. Using LaAlO3/SrTiO3 as a model system, we
      demonstrate controllable electrostatic confinement of electrons to nanoscale
      regions in the conducting interface. The excellent gate response, ultralow
      leakage currents, and long-term stability of these gates allow us to perform a
      variety of studies in different device geometries from room temperature down to
      50 mK. Using a split-gate device we demonstrate the formation of a narrow
      conducting channel whose width can be controllably reduced via the application of
      appropriate gate voltages. We also show that a single narrow gate can be used to
      induce locally a superconducting to insulating transition. Furthermore, in the
      superconducting regime we see indications of a gate-voltage controlled Josephson
      effect. 

PMID- 25749274
TI  - Joint effect of CENTD2 and KCNQ1 polymorphisms on the risk of type 2 diabetes
      mellitus among Chinese Han population.
AB  - Genome-wide association studies (GWAS) in populations of European ancestry have
      identified nine single nuclear polymorphisms (SNP) on chromosome 11 related to
      type 2 diabetes (T2D) susceptibility. Herein, we further evaluate the association
      of these SNPs and T2D in a Chinese Han population. We performed a case-control
      study of 2925 T2D cases and 3281 controls to evaluate the association of five
      SNPs of KCNJ11, MTNR1B, CENTD2 and LOC387761 and T2D in addition to the
      previously reported four SNPs of KCNQ1. Multiple logistic regression was used to
      evaluate SNP's effect by adjustment for confounding factor age, sex and BMI. In
      the first stage, SNPs rs1552224 at CENTD2 were significantly associated with T2D
      and the association was statistically significant in the whole study population
      (P = 0.001) although it was not replicated in the second stage. rs1552224 and
      rs2237897 of KCNQ1 showed significant joint effect on T2D and there was a
      significant decreased risk of T2D with the number increase of risk alleles (P for
      trend = 3.81 * 10(-17)). Compared to those without carrying any risk allele,
      individuals carrying one, two, and three or four risk alleles had a 30.7%, 44.8%
      and 62.0% decreased risk for developing T2D, respectively. Our finding suggests
      that genetic variant rs1552224 of CENTD2 on chromosome 11 contributes to an
      independent effect as well as joint cumulative effect with rs2237897 of KCNQ1 on
      the risk of T2D in Chinese Han population, and further functional research would
      be warranted.

PMID- 25749275
TI  - Altered transition metal homeostasis in the cuprizone model of demyelination.
AB  - In the cuprizone model of demyelination, the neurotoxin cuprizone is fed to mice
      to induce a reproducible pattern of demyelination in the brain. Cuprizone is a
      copper chelator and it has been hypothesized that it induces a copper deficiency
      in the brain, which leads to demyelination. To test this hypothesis and
      investigate the possible role of other transition metals in the model, we fed
      C57Bl/6 mice a standard dose of cuprizone (0.2% dry chemical to dry food weight)
      for 6 weeks then measured levels of copper, manganese, iron, and zinc in regions
      of the brain and visceral organs. As expected, this treatment induced
      demyelination in the mice. We found, however, that while the treatment
      significantly reduced copper concentrations in the blood and liver in treated
      animals, there was no significant difference in concentrations in brain regions
      relative to control. Interestingly, cuprizone disrupted concentrations of the
      other transition metals in the visceral organs, with the most notable changes
      being decreased manganese and increased iron in the liver. In the brain,
      manganese concentrations were also significantly reduced in the cerebellum and
      striatum. These data suggest a possible role of manganese deficiency in the brain
      in the cuprizone model. 

PMID- 25749276
TI  - In situ nasal gel drug delivery: A novel approach for brain targeting through the
      mucosal membrane.
AB  - Recently, sustained and controlled drug delivery has become the demand, and
      research has been undertaken in achieving much better drug product effectiveness,
      reliability and safety. The in situ polymeric system has gained much attention,
      to develop a controlled release system. It has been used as a vehicle for local
      and systemic drug delivery. Nowadays, it has created much interest, because of
      its characteristics of high vascularization, high permeability, rapid onset of
      action, low enzymatic degradation, and avoidance of hepatic first pass
      metabolism. The main aim of this review is to provide knowledge of different
      mechanisms of nasal absorption and approaches for nasal drug delivery. 

PMID- 25749277
TI  - Ibuprofen microencapsulation within acrylamide-grafted chitosan and
      methylcellulose interpenetrating polymer network microspheres: Synthesis,
      characterization, and release studies.
AB  - This study deals with the development of interpenetrating polymer network (IPN)
      microspheres of acrylamide (AAm) grafted onto a chitosan (CS) backbone and
      methylcellulose (MC). Chitosan-graft-polyacrylamide (CS-g-PAAm) was synthesized
      by cerium (IV) ammonium nitrate-induced free radical graft polymerization. The
      grafting percentage was found to be 50.58%. The synthesized graft copolymer and
      MC were used to prepare microspheres by the water-in-oil (w/o) emulsion
      crosslinking method, and crosslinked with glutaraldehyde (GA) as drug delivery
      matrices of ibuprofen (IBU). The release of IBU from microspheres decreased when
      the amount of CS-g-PAAm in the polymer matrix and amount of crosslinker added
      were increased, while it increased with the increase of the IBU/polymer ratio. 

PMID- 25749278
TI  - The effect of silver nanoparticles on zebrafish embryonic development and
      toxicology.
AB  - The unique physical and chemical characteristics of nanomaterials, such as the
      effects of their small size, surface effects, very high rates of reaction, and
      quantum tunnel effect, have aroused great interest among scholars. However,
      improper usage has led to an increasing number of nanomaterials entering the
      environment through various channels, greatly threatening the security of the
      ecological environment and human health. The urgent need for a scientific
      assessment of their biosafety can enable nanomaterials to truly benefit humanity.
      However, the current research in this field is extremely limited with regard to
      safety standards and waste disposal. In this study, we used silver nanoparticles
      (nano-Ag) and zebrafish embryos as experimental subjects, and we have reported
      the deleterious effect on zebrafish embryos treated with different concentrations
      of nano-Ag, with respect to morphological features (mortality, deformity rate,
      and heartbeat) and the analysis of expression of relevant genes (sox17, gsc, ntl,
      otx2); we found a dose-dependent increase in mortality and hatching delay. The
      results of in situ hybridization indicated that nano-Ag causes a dose-dependent
      toxicity in embryonic development, and would affect their development and lead to
      deformity, delayed development, and even death. The safety limit for the
      concentration of nano-Ag was found to be less than 5 mg/L. 

PMID- 25749279
TI  - The effect of cationic starch on hemoglobin, and the primary attempt to
      encapsulate hemoglobin.
AB  - Though starch has been a common material used for drug delivery, it has not been
      used as an encapsulation material for hemoglobin-based oxygen carriers. In this
      study, cationic amylose (CA) was synthesized by an etherification reaction. The
      interaction behaviors between CA and hemoglobin (Hb) were measured by zeta
      potential, size, and UV-Vis absorption spectra at different pH values. Cationic
      starch encapsulated Hb by electrostatic adhesion, reverse micelles, and cross
      linking, and showed a core shell structure with a size of around 100 nm, when
      measured immediately after dispersing in PBS solution. However, we found that it
      was prone to swell, aggregate, and leak Hb with a longer duration of dispersal in
      PBS. 

PMID- 25749280
TI  - Synthesis of a specific monolithic column with artificial recognition sites for L
      glutamic acid via cryo-crosslinking of imprinted nanoparticles.
AB  - In this study, a new molecular imprinting (MIP)-based monolithic cryogel column
      was prepared using chemically crosslinked molecularly imprinted nanoparticles, to
      achieve a simplified chromatographic separation (SPE) for a model compound, L
      glutamic acid (L-Glu). Cryogelation through crosslinking of imprinted
      nanoparticles forms stable monolithic cryogel columns. This technique reduces the
      leakage of nanoparticles and increases the surface area, while protecting the
      structural features of the cryogel for stable and efficient recognition of the
      template molecule. A non-imprinted monolithic cryogel column (NIP) was also
      prepared, using non-imprinted nanoparticles produced without the addition of L
      Glu during polymerization. The molecularly imprinted monolithic cryogel column
      (MIP) indicates apparent recognition selectivity and a good adsorption capacity
      compared to the NIP. Also, we have achieved a significant increase in the
      adsorption capacity, using the advantage of high surface area of the
      nanoparticles. 

PMID- 25749281
TI  - Green synthesis of silver nanoparticles by Bacillus methylotrophicus, and their
      antimicrobial activity.
AB  - The synthesis of silver nanoparticles (AgNPs) by microorganisms is an area
      attracting growing interest in nanobiotechnology, due to the applications of
      these nanoparticles in various products including cosmetics and biosensors, and
      in the biomedical, clinical, and bioimaging fields as well. Various
      microorganisms have been found to be able to synthesize AgNPs when silver salts
      are supplied in the reaction system. The main objectives of this study were to
      evaluate the efficiency of synthesis of AgNPs by the strain Bacillus
      methylotrophicus DC3, isolated from the soil of Korean ginseng, a traditionally
      known oriental medicinal plant in Korea. The AgNPs showed maximum absorbance at
      416 nm, when assayed by ultraviolet-visible spectroscopy (UV-vis). The field
      emission transmission electron micrograph (FE-TEM) results showed that the
      particles were spherical and 10-30 nm in size. In addition, the product was also
      characterized by energy dispersive X-ray spectroscopy (EDX), which displayed a 3
      keV peak corresponding to the silver nanocrystal. Elemental mapping results also
      confirmed the presence of silver elements in the electron micrograph region.
      Furthermore, the AgNPs demonstrated antimicrobial activity against various
      pathogenic microorganisms such as Candida albicans, Salmonella enterica,
      Escherichia coli, and Vibrio parahaemolyticus, with enhanced antimicrobial
      activity being exhibited against C. albicans. Therefore, the current study
      describes the simple, efficient, and green method of synthesis of AgNPs by B.
      methylotrophicus DC3. 

PMID- 25749282
TI  - Characterization and biological abatement of diffuse methane emissions and odour
      in an innovative wastewater treatment plant.
AB  - An innovative and patented process for medium-high strength sewage which
      comprises an anaerobic step followed by a hybrid anoxic-aerobic chamber and a
      final ultrafiltration stage was characterized in terms of methane fugitive
      emissions as well as odours. The operation at ambient temperature implies higher
      methane content in the liquid anaerobic effluent, which finally causes
      concentrations around 0.01-2.4% in the off-gas released in the anoxic-aerobic
      chamber (1.25% average). Mass balances indicate that these emissions account for
      up to 30-35% of the total methane generated in the anaerobic reactor. A
      conventional biofilter (BF) operated at an empty bed residence time of 4 min was
      used to treat these emissions for 70 d. In spite of the fluctuations in the
      methane inlet concentrations derived from the operation of the wastewater
      treatment plant (WWTP), it was possible to operate at pseudo-steady-state
      conditions, achieving average removal efficiencies of 76.5% and maximum
      elimination capacities of 30.1 g m(-3) h(-1). Odour removal was quantified as
      99.1%. Fluorescence in situ hybridization probes as well as metabolic activity
      assays demonstrated the suitability of the biomass developed in the WWTP as
      inoculum to start up the BF due to the presence of methanotrophic bacteria.

PMID- 25749283
TI  - Measurement of waist and hip circumference with a body surface scanner:
      feasibility, validity, reliability, and correlations with markers of the
      metabolic syndrome.
AB  - OBJECTIVE: Body surface scanners (BS), which visualize a 3D image of the human
      body, facilitate the computation of numerous body measures, including height,
      waist circumference (WC) and hip circumference (HC). However, limited information
      is available regarding validity and reliability of these automated measurements
      (AM) and their correlation with parameters of the Metabolic Syndrome (MetS)
      compared to traditional manual measurements (MM). METHODS: As part of a cross
      sectional feasibility study, AM of WC, HC and height were assessed twice in 60
      participants using a 3D BS (VitussmartXXL). Additionally, MM were taken by
      trained personnel according to WHO guidelines. Participants underwent an
      interview, bioelectrical impedance analysis, and blood pressure measurement.
      Blood samples were taken to determine HbA1c, HDL-cholesterol, triglycerides, and
      uric acid. Validity was assessed based on the agreement between AM and MM, using
      Bland-Altman-plots, correlation analysis, and paired t-tests. Reliability was
      assessed using intraclass correlation coefficients (ICC) based on two repeated
      AM. Further, we calculated age-adjusted Pearson correlation for AM and MM with
      fat mass, systolic blood pressure, HbA1c, HDL-cholesterol, triglycerides, and
      uric acid. RESULTS: Body measures were higher in AM compared to MM but both
      measurements were strongly correlated (WC, men, difference = 1.5 cm, r = 0.97;
      women, d = 4.7 cm, r = 0.96; HC, men, d = 2.3 cm, r = 0.97; women, d = 3.0 cm; r
      = 0.98). Reliability was high for all AM (nearly all ICC>0.98). Correlations of
      WC, HC, and the waist-to-hip ratio (WHR) with parameters of MetS were similar
      between AM and MM; for example the correlation of WC assessed by AM with HDL
      cholesterol was r = 0.35 in men, and r = -0.48 in women, respectively whereas
      correlation of WC measured manually with HDL cholesterol was r = -0.41 in men,
      and r = -0.49 in women, respectively. CONCLUSIONS: Although AM of WC, HC, and WHR
      are higher when compared to MM based on WHO guidelines, our data indicate good
      validity, excellent reliability, and similar correlations to parameters of the
      MetS.

PMID- 25749284
TI  - Organizer regions in marine colonial hydrozoans.
AB  - Organizers are specific tissue regions of developing organisms that provide
      accuracy and robustness to the body plan formation. Hydrozoan cnidarians (both
      solitary and colonial) require organizer regions for maintaining the regular body
      patterning during continuous tissue dynamics during asexual reproduction and
      growth. While the hypostomal organizer of the solitary Hydra has been studied
      relatively well, our knowledge of organizers in colonial hydrozoans remains
      fragmentary and incomplete. As colonial hydrozoans demonstrate an amazing
      diversity of morphological and life history traits, it is of special interest to
      investigate the organizers specific for particular ontogenetic stages and
      particular types of colonies. In the present study we aimed to assess the
      inductive capacities of several candidate organizer regions in hydroids with
      different colony organization. We carried out grafting experiments on colonial
      hydrozoans belonging to Leptothecata and Anthoathecata. We confirmed that the
      hypostome tip is an organizer in the colonial Anthoathecata as it is in the
      solitary polyp Hydra. We also found that the posterior tip of the larva is an
      organizer in hydroids regardless of the peculiarities of their metamorphosis mode
      and colony structure. We show for the first time that the shoot growing tip,
      which can be considered a key evolutionary novelty of Leptothecata, is an
      organizer region. Taken together, our data demonstrate that organizers function
      throughout the larval and polypoid stages in colonial hydroids. 

PMID- 25749285
TI  - Arteria praebronchialis found on MDCT: potentially dangerous aberrant artery
      supplying the left lower lobe.
AB  - PURPOSE: To describe the incidence and CT features of a rare branching pattern of
      the pulmonary artery, the Arteria praebronchialis (AP): According to the initial
      description, the AP originates as the first branch of the left pulmonary artery,
      crosses the front of the left mainstem bronchus and then runs along the
      mediastinal margin as it gives off branches to one or more of the basal segments.
      MATERIALS AND METHODS: Since the incidental discovery of the first patient,
      contrast-enhanced CT was screened by one radiologist for the presence of AP,
      until three more cases were identified. In those four patients, segmental and
      lobar branching patterns of the AP were assessed. RESULTS: The estimated
      incidence of the AP was 0.03%. All four patients were men. Compared to the normal
      interlobar artery, the AP was smaller (n = 2), larger (n = 1), or of an equal
      size (n = 1). The segmental branches of the AP to the upper lobe (present in
      three patients) were A3 and A4 (n = 1), A3 and A5 (n = 1) and A4+5 (n = 1),
      respectively. Regarding the supply of the left lower lobe, AP gave off A7+8 and
      A9 (n = 2), A7+8 (n = 1), and A7 and A10 (n = 1), respectively. In two patients,
      a contralateral variant of pulmonary arterial branching was found, with (right)
      A7 arising as the first branch of right pulmonary artery. CONCLUSION: The AP is
      extremely rare, but has a strong male predilection and highly diverse branching
      patterns in both the current study and the literature. Radiologists should
      familiarize themselves with the CT features of this surgically important
      variation, and be able to describe its lobar and segmental blood supply.

PMID- 25749286
TI  - [New operative intervention in adenocarcinoma of the rhinopharynx].
AB  - Polymorphous low-grade adenocarcinoma is a rare tumour of the rhinopharynx. This
      is a case report of a 32-year-old Danish man who was treated by primary surgical
      excision in Hong Kong via the maxillary swing approach and post-operative
      irradiation therapy in Denmark. Since September 2012 this surgical modality has
      been offered at Rigshospitalet in Copenhagen. 

PMID- 25749287
TI  - [Analysis of medical short-term admissions of elderly patients with focus on
      alternatives to hospitalization].
AB  - By a retrospective medical record review it is studied if 334 admissions of acute
      short-term hospitalization (< 24 hours) of elderly medical patients could have
      been substituted by alternative solutions. 27% of these admissions were evaluated
      as substitutable. This study cannot confirm that the number of medical short-term
      admissions of elderly patients could be reduced by one or more specific
      interventions, nor that the medical short-term hospitalization generally is
      inappropriate. 

PMID- 25749288
TI  - [Sexual dysfunction is frequent in patients with anal fistulas and anal
      fissures].
AB  - Anal fistulas and fissures are frequent disorders. Affected patients may have
      significant psychosocial and sexual dysfunction. A few studies have investigated
      patients with anal fissures and fistulas with regard to sexual dysfunction. These
      studies showed a significant degree of sexual dysfunction among the affected
      patients. Data are surprisingly limited in this field. More studies are needed to
      describe this issue and to define a successful treatment for these patients. 

PMID- 25749289
TI  - [Certain opioids can preferably be administered transdermally].
AB  - Many patients experience acute or chronic pain. The options for treating these
      pain conditions are many, and particularly products for topical application are
      gaining ground. NSAID for topical use is a good alternative to NSAID administered
      orally due to less systemic side effects. Transdermally delivered opioids have
      proven to be as effective as morphine in pain management of chronic, moderate to
      severe pain. The steady delivery and lower risk of breakthrough pain overweigh
      the higher cost and risk of adverse events compared to the orally delivered
      opioids. 

PMID- 25749290
TI  - [Perivascular epithelioid cell tumours in the liver].
AB  - The PEComa family is a group of tumours having perivascular epithelioid cells
      (PEC) as the predominating component. PEComas occur in various organs and are
      considered to be benign tumours. However, rare cases showing pleomorphic
      morphology, atypical mitoses or necrosis should be considered malignant sarcomas.
      The precise incidence is unknown but PEComas are reported with increasing
      frequency. Standard treatment is surgery but there are no guidelines on further
      follow-up or treatment. PEComa in the liver is a rare tumour, and to our
      knowledge this is the first published case from Denmark. 

PMID- 25749291
TI  - Mechanical properties of endothelialized fibroblast-derived vascular scaffolds
      stimulated in a bioreactor.
AB  - There is an ongoing clinical need for tissue-engineered small-diameter (<6mm)
      vascular grafts since clinical applications are restricted by the limited
      availability of autologous living grafts or the lack of suitability of synthetic
      grafts. The present study uses our self-assembly approach to produce a fibroblast
      derived decellularized vascular scaffold that can then be available off-the
      shelf. Briefly, scaffolds were produced using human dermal fibroblasts sheets
      rolled around a mandrel, maintained in culture to allow for the formation of
      cohesive and three-dimensional tubular constructs, and then decellularized by
      immersion in deionized water. Constructs were then endothelialized and perfused
      for 1week in an appropriate bioreactor. Mechanical testing results showed that
      the decellularization process did not influence the resistance of the tissue and
      an increase in ultimate tensile strength was observed following the perfusion of
      the construct in the bioreactor. These fibroblast-derived vascular scaffolds
      could be stored and later used to deliver readily implantable grafts within
      4weeks including an autologous endothelial cell isolation and seeding process.
      This technology could greatly accelerate the clinical availability of tissue
      engineered blood vessels. 

PMID- 25749292
TI  - Orientation and conformation of anti-CD34 antibody immobilised on untreated and
      plasma treated polycarbonate.
AB  - The conformation and orientation of proteins immobilised on synthetic materials
      determine their ability to bind their antigens and thereby the sensitivity of the
      microarrays and biosensors employing them. Plasma immersion ion implantation
      (PIII) of polymers significantly increases both their wettability and protein
      binding capacity. This paper addresses the hypothesis that a PIII treated polymer
      surface modifies the native protein conformation less significantly than a more
      hydrophobic untreated surface and that the differences in surface properties also
      affect the protein orientation. To prove this, the orientation and conformation
      of rat anti-mouse CD34 antibody immobilized on untreated and PIII treated
      polycarbonate (PC) were investigated using ToF-SIMS and FTIR-ATR spectroscopy.
      Analysis of the primary structure of anti-CD34 antibody and principal component
      analysis of ToF-SIMS data were applied to detect the difference in the
      orientation of the antibody attached to untreated and PIII treated PC. The
      difference in the antibody conformation was analysed using deconvolution of the
      Amide I peak (in FTIR-ATR spectra) and curve-fitting. It was found that compared
      to the PIII treated sample, the antibody immobilized on the untreated PC sample
      has a secondary structure with a lower fraction of beta-sheets and a higher
      fraction of alpha-helices and disordered fragments. Also, it was found that anti
      CD34 antibody has a higher tendency to occur in the inactive 'tail-up'
      orientation when immobilized on an untreated PC surface than on a PIII treated
      surface. These findings confirm the above hypothesis. 

PMID- 25749293
TI  - Antibacterial activity of chitosan nanofiber meshes with liposomes immobilized
      releasing gentamicin.
AB  - Chitsan (Ch) nanofiber mesh (NFM) is a material with natural characteristics
      favoring its use in human wound dressing. The present work proposes a gentamicin
      loaded liposome immobilized at the surface of Ch NFMs to promote its
      antibacterial activity. To achieve this purpose, Ch NFMs were functionalized with
      thiol groups, and gentamicin-loaded liposomes were covalently immobilized by the
      reaction of the SH groups with maleimide. The maximum concentration of SH groups
      (55.52+/-11.19nmolcm(-2)) was obtained at pH 7. A fluorescent dye was covalently
      bound to the SH groups present at the surface of electrospun Ch NFMs. Their
      spatial distribution was uniform throughout the NFMs when analyzed by
      fluorescence microscopy. Gentamicin was successfully encapsulated into the
      liposomes with an efficiency of 17%. Gentamicin-loaded liposomes were uniformly
      distributed at the surface of the Ch NFMs and the drug release kinetic showed a
      sustained release of gentamicin during 16h, achieving a steady state at 24h. The
      in vitro susceptibility tests confirmed that the gentamicin released from the
      liposomes immobilized at the surface of electrospun Ch NFM has bactericidal
      activity against Escherichia coli, Pseudomonas aeruginosa and Staphylococcus
      aureus. The results show that the developed system has promising performance for
      wound dressing applications, avoiding infections caused by these common
      pathogens. 

PMID- 25749294
TI  - Water-soluble photopolymerizable chitosan hydrogels for biofabrication via two
      photon polymerization.
AB  - Fabrication of three-dimensional (3D) hydrogel microenvironments with predefined
      geometry and porosity can facilitate important requirements in tissue engineering
      and regenerative medicine. Chitosan (CH) is well known as a biocompatible
      hydrogel with prospective biological properties for biomedical aims. So far,
      microstructuring of this soft material presents a great limitation for its
      application as functional supporting material for guided tissue formation.
      Enabling photopolymerization, chemically modified CH can be applied for the
      biofabrication of reproducible 3D scaffolds using rapid prototyping techniques
      like two-photon polymerization (2PP) or others. The application of this technique
      allows precise serial fabrication of computer-designed microstructure geometries
      by scanning a femtosecond laser beam within a photosensitive material. This work
      explores a new synthesis of water-soluble photosensitive chitosan and the
      fabrication of well-defined microstructures from the generated materials. To
      modulate the mechanical and biochemical properties of the material, CH was
      combined and cross-linked with synthetic poly(ethylene glycol) diacrylate. For a
      biological adaption to the in vivo situation, CH was covalently crosslinked with
      a photosensitive modified vascular endothelial growth factor (VEGF). Performed in
      vitro studies reveal that modified CH is biocompatible. VEGF enhances CH
      bioactivity. Furthermore, a 3D CH scaffold can be successfully seeded with cells.
      Therefore, the established CH holds great promise for future applications in
      tissue engineering. 

PMID- 25749295
TI  - Fabrication of modular multifunctional delivery for antitumor drugs based on host
      guest recognition.
AB  - Herein, learning from the idea of the modular concept widely used in ship
      building, as a design approach that assembles some subdivided smaller modules to
      a specific ship, a new modular multifunctional drug delivery (MMDD) with
      excellent biocompatibility was directly prepared by a flexible host-guest
      interaction between pH-sensitive benzimidazole-graft-dextran (Dex-BM) and pre
      synthesized multifunctional cyclodextrins. In this drug system, pH-sensitive Dex
      BM acted as the main case and pre-synthesized multifunctional cyclodextrins were
      the changeable modules. To verify the feasibility of MMDD in cancer chemotherapy,
      doxorubicin (DOX) was used as a model drug. In vitro drug release experiments
      indicated that the drug released around 80% from DOX-loaded MMDD at pH 5.3, while
      approximately 40% of DOX released under the condition of pH 7.4. Moreover, the
      targeting antitumor activity of DOX-loaded MMDD was investigated in HeLa and
      HepG2 cells using MTT assays, confocal laser scanning microscopy and flow
      cytometer, which indicated that the targeted DOX-loaded MMDD provided an
      efficient drug delivery platform for inhibition of different cancer cells.
      Meantime, the incorporation of different functional modules into one system was
      also investigated, simultaneously exhibiting targeting and imaging property.
      These features suggest that this modular multifunctional drug delivery system can
      efficiently enhance the inhibition of cellular proliferation in vitro, and
      according to the needs in clinical treatment, some targeting and imaging
      molecules can be chosen. 

PMID- 25749296
TI  - Enzymatic regulation of functional vascular networks using gelatin hydrogels.
AB  - To manufacture tissue engineering-based functional tissues, scaffold materials
      that can be sufficiently vascularized to mimic the functionality and complexity
      of native tissues are needed. Currently, vascular network bioengineering is
      largely carried out using natural hydrogels as embedding scaffolds, but most
      natural hydrogels have poor mechanical stability and durability, factors that
      critically limit their widespread use. In this study, we examined the suitability
      of gelatin-phenolic hydroxyl (gelatin-Ph) hydrogels that can be enzymatically
      crosslinked, allowing tuning of the storage modulus and the proteolytic
      degradation rate, for use as injectable hydrogels to support the human progenitor
      cell-based formation of a stable and mature vascular network. Porcine gelatin-Ph
      hydrogels were found to be cytocompatible with human blood-derived endothelial
      colony-forming cells and white adipose tissue-derived mesenchymal stem cells,
      resulting in >87% viability, and cell proliferation and spreading could be
      modulated by using hydrogels with different proteolytic degradability and
      stiffness. In addition, gelatin was extracted from mouse dermis and murine
      gelatin-Ph hydrogels were prepared. Importantly, implantation of human cell-laden
      porcine or murine gelatin-Ph hydrogels into immunodeficient mice resulted in the
      rapid formation of functional anastomoses between the bioengineered human
      vascular network and the mouse vasculature. Furthermore, the degree of enzymatic
      crosslinking of the gelatin-Ph hydrogels could be used to modulate cell behavior
      and the extent of vascular network formation in vivo. Our report details a
      technique for the synthesis of gelatin-Ph hydrogels from allogeneic or xenogeneic
      dermal skin and suggests that these hydrogels can be used for biomedical
      applications that require the formation of microvascular networks, including the
      development of complex engineered tissues. 

PMID- 25749297
TI  - Darapladib, a lipoprotein-associated phospholipase A2 inhibitor, in diabetic
      macular edema: a 3-month placebo-controlled study.
AB  - PURPOSE: To investigate the potential of lipoprotein-associated phospholipase A2
      inhibition as a novel mechanism to reduce edema and improve vision in center
      involved diabetic macular edema (DME). DESIGN: Prospective, multicenter,
      randomized, double-masked, placebo-controlled phase IIa study. PARTICIPANTS:
      Fifty-four center-involved DME patients randomized 2:1 to receive darapladib (n =
      36) or placebo (n = 18). METHODS: Darapladib 160 mg or placebo monotherapy was
      administered orally once daily for 3 months, and patients were followed up
      monthly for 4 months. MAIN OUTCOME MEASURES: Mean change from baseline in best
      corrected visual acuity (BCVA) and the center subfield and center point of the
      study eye at month 3 as determined by spectral-domain optical coherence
      tomography. RESULTS: Five patients in the study received intravitreal anti
      vascular endothelial growth factor rescue therapy before the day 90 assessment, 2
      of 36 (6%) in the darapladib arm and 3 of 18 (17%) in the placebo arm.
      Administration of 160 mg darapladib for 3 months resulted in statistically
      significant mean improvements, from baseline to month 3, in BCVA of 4.1 Early
      Treatment Diabetic Retinopathy Study (ETDRS) letters (95% confidence interval
      [CI], 2.3-5.8) and of 57 MUm in central subfield thickness (95% CI, -84 to -30)
      in the study eyes. An increase in BCVA of 1.7 ETDRS letters (95% CI, -1.0 to 4.4)
      and a decrease in center subfield thickness of 34 MUm (95% CI, -75 to 6.8) for
      the placebo group were not significant. No ocular severe adverse events (SAEs) or
      SAEs considered related to darapladib were reported. One SAE of myocardial
      infarction, not considered related to darapladib, was reported, and 1 SAE of
      severe diarrhea was reported in a placebo patient, subsequently withdrawn from
      the study. Study eye ocular adverse events (AEs) and nonocular AEs were similar
      between treatment groups. CONCLUSIONS: Once-daily oral darapladib administered
      for 3 months demonstrated modest improvements in vision and macular edema that
      warrant additional investigation of this novel lipoprotein-associated
      phospholipase A2 inhibitory mechanism for the treatment of DME.

PMID- 25749298
TI  - Core-shell Ti@Si coaxial nanorod arrays formed directly on current collectors for
      lithium-ion batteries.
AB  - Silicon is a promising candidate to replace the dominantly used carbon as the
      anode material for lithium ion batteries (LIBs). Si has the highest theoretical
      capacity (4200 mA.h/g) and is one of the most abundant elements. Unfortunately,
      Si has the issues of huge volume variation upon dis/charge cycling and low
      conductivity, leading to poor cycling and rate performances. Designing special
      nanostructures and improving conductivity and integration of Si electrodes could
      dramatically enhance their performance. Here, we introduce a novel strategy to
      integrate the core-shell nanorod arrays of Ti@Si on Ti foil with good
      conductivity as an additive-free electrode. The Ti core functions as a stable
      metallic support for the Si shell and dramatically reduces the diffusion length.
      The as-prepared core-shell nanorod arrays of Ti@Si on Ti foil, without any
      postsynthesis treatment, as electrodes demonstrated reversible capacity of 1125
      mA.h/g over at least 30 cycles with highly improved Coulombic efficiency. 

PMID- 25749300
TI  - Abstracts of the 33rd Annual Meeting of the European Malignant Hyperthermia Group
      (EMHG), May15-17, 2014, Wurzburg, Germany.

PMID- 25749299
TI  - TAAR1 Modulates Cortical Glutamate NMDA Receptor Function.
AB  - Trace Amine-Associated Receptor 1 (TAAR1) is a G protein-coupled receptor
      expressed in the mammalian brain and known to influence subcortical monoaminergic
      transmission. Monoamines, such as dopamine, also play an important role within
      the prefrontal cortex (PFC) circuitry, which is critically involved in high
      o5rder cognitive processes. TAAR1-selective ligands have shown potential
      antipsychotic, antidepressant, and pro-cognitive effects in experimental animal
      models; however, it remains unclear whether TAAR1 can affect PFC-related
      processes and functions. In this study, we document a distinct pattern of
      expression of TAAR1 in the PFC, as well as altered subunit composition and
      deficient functionality of the glutamate N-methyl-D-aspartate (NMDA) receptors in
      the pyramidal neurons of layer V of PFC in mice lacking TAAR1. The dysregulated
      cortical glutamate transmission in TAAR1-KO mice was associated with aberrant
      behaviors in several tests, indicating a perseverative and impulsive phenotype of
      mutants. Conversely, pharmacological activation of TAAR1 with selective agonists
      reduced premature impulsive responses observed in the fixed-interval conditioning
      schedule in normal mice. Our study indicates that TAAR1 plays an important role
      in the modulation of NMDA receptor-mediated glutamate transmission in the PFC and
      related functions. Furthermore, these data suggest that the development of TAAR1
      based drugs could provide a novel therapeutic approach for the treatment of
      disorders related to aberrant cortical functions. 

PMID- 25749301
TI  - High incubation temperatures enhance mitochondrial energy metabolism in reptile
      embryos.
AB  - Developmental rate increases exponentially with increasing temperature in
      ectothermic animals, but the biochemical basis underlying this thermal dependence
      is largely unexplored. We measured mitochondrial respiration and metabolic enzyme
      activities of turtle embryos (Pelodiscus sinensis) incubated at different
      temperatures to identify the metabolic basis of the rapid development occurring
      at high temperatures in reptile embryos. Developmental rate increased with
      increasing incubation temperatures in the embryos of P. sinensis.
      Correspondingly, in addition to the thermal dependence of mitochondrial
      respiration and metabolic enzyme activities, high-temperature incubation further
      enhanced mitochondrial respiration and COX activities in the embryos. This
      suggests that embryos may adjust mitochondrial respiration and metabolic enzyme
      activities in response to developmental temperature to achieve high developmental
      rates at high temperatures. Our study highlights the importance of biochemical
      investigations in understanding the proximate mechanisms by which temperature
      affects embryonic development. 

PMID- 25749303
TI  - Identification of DNA-binding proteins that interact with the 5'-flanking region
      of the human D-amino acid oxidase gene by pull-down assay coupled with two
      dimensional gel electrophoresis and mass spectrometry.
AB  - D-Amino acid oxidase (DAO) is a flavoenzyme that metabolizes D-amino acids and is
      expected to be a promising therapeutic target of schizophrenia and glioblastoma.
      The study of DNA-binding proteins has yielded much information in the regulation
      of transcription and other biological processes. However, proteins interacting
      with DAO gene have not been elucidated. Our assessment of human DAO promoter
      activity using luciferase reporter system indicated the 5'-flanking region of
      this gene (-4289 bp from transcription initiation site) has a regulatory sequence
      for gene expression, which is regulated by multi-protein complexes interacting
      with this region. By using pull-down assay coupled with two-dimensional gel
      electrophoresis and mass spectrometry, we identified six proteins binding to the
      5'-flanking region of the human DAO gene (zinc finger C2HC domain-containing
      protein 1A; histidine-tRNA ligase, cytoplasmic; molybdenum cofactor biosynthesis
      protein; 60S ribosomal protein L37; calponin-1; calmodulin binding protein and
      heterogeneous nuclear ribonucleoprotein A2/B1). These preliminary results will
      contribute to the advance in the understanding of the potential factors
      associated with the regulatory mechanism of DAO expression.

PMID- 25749302
TI  - Mesial temporal lobe and memory function in autism spectrum disorder: an
      exploration of volumetric findings.
AB  - Studies have shown that individuals with autism spectrum disorder (ASD) tend to
      perform significantly below typical developing individuals on standardized
      measures of memory, even when not significantly different on measures of IQ. The
      current study sought to examine within ASD whether anatomical correlates of
      memory performance differed between those with average-to-above-average IQ (AIQ
      group) and those with low-average to borderline ability (LIQ group) as well as in
      relations to typically developing comparisons (TDC). Using automated volumetric
      analyses, we examined regional volume of classic memory areas including the
      hippocampus, parahippocampal gyrus, entorhinal cortex, and amygdala in an all
      male sample AIQ (n = 38) and LIQ (n = 18) individuals with ASD along with 30
      typically developing comparisons (TDC). Memory performance was assessed using the
      Test of Memory and Learning (TOMAL) compared among the groups and then correlated
      with regional brain volumes. Analyses revealed group differences on almost all
      facets of memory and learning as assessed by the various subtests of the TOMAL.
      The three groups did not differ on any region of interest (ROI) memory-related
      brain volumes. However, significant size-memory function interactions were
      observed. Negative correlations were found between the volume of the amygdala and
      composite, verbal, and delayed memory indices for the LIQ ASD group, indicating
      larger volume related to poorer performance. Implications for general memory
      functioning and dysfunctional neural connectivity in ASD are discussed. 

PMID- 25749304
TI  - Immunohistochemical localization of D-beta-aspartic acid-containing proteins in
      pterygium.
AB  - Biologically uncommon D-beta-aspartic acid (D-beta-Asp) residues have been
      reported to accumulate in organs affected by age-related disorders. In the
      present study, we investigated the localization of D-beta-Asp-containing proteins
      in cases of pterygium, one of the most prominent age-related ocular conditions.
      Immunohistochemical localization of D-beta-Asp-containing proteins was
      investigated in surgical specimens of pterygium from 20 patients and control
      specimens from 10 patients. Strong immunoreactivity to D-beta-Asp-containing
      proteins was observed in subepithelial elastotic lesions and surrounding
      collagenous lesions from all surgical specimens with pterygia. In contrast, no
      immunoreactivity to D-beta-Asp-containing proteins was seen in pterygium-free
      specimens. D-beta-Asp-containing proteins are produced in organs as they are
      affected by the aging process. In addition, conversion of L- to D-aspartyl
      residues is accelerated by ultraviolet (UV) irradiation. Since pterygia can form
      due to aging or UV exposure, it is reasonable to find D-beta-Asp-containing
      proteins in specimens with pterygia. Furthermore, since D-beta-Asp is a non
      native amino acid, D-beta-Asp-containing proteins may be recognized as allogeneic
      antigens. Therefore, D-beta-Asp-containing proteins in pterygia may responsible
      for the fibrovascular changes seen in the disorder.

PMID- 25749305
TI  - Microglial interleukin-1beta in the ipsilateral dorsal horn inhibits the
      development of mirror-image contralateral mechanical allodynia through astrocyte
      activation in a rat model of inflammatory pain.
AB  - Damage on one side of the body can also result in pain on the contralateral
      unaffected side, called mirror-image pain (MIP). Currently, the mechanisms
      responsible for the development of MIP are unknown. In this study, we
      investigated the involvement of spinal microglia and interleukin-1beta (IL-1beta)
      in the development of MIP using a peripheral inflammatory pain model. After
      unilateral carrageenan injection, mechanical allodynia (MA) in both hind paws and
      the expression levels of spinal Iba-1, IL-1beta, and GFAP were evaluated.
      Ipsilateral MA was induced beginning at 3 hours after carrageenan injection,
      whereas contralateral MA showed a delayed onset occurring 5 days after injection.
      A single intrathecal (i.t.) injection of minocycline, a tetracycline derivative
      that displays selective inhibition of microglial activation, or an interleukin-1
      receptor antagonist (IL-1ra) on the day of carrageenan injection caused an early
      temporary induction of contralateral MA, whereas repeated i.t. treatment with
      these drugs from days 0 to 3 resulted in a long-lasting contralateral MA, which
      was evident in its advanced development. We further showed that IL-1beta was
      localized to microglia and that minocycline inhibited the carrageenan-induced
      increases in spinal Iba-1 and IL-1beta expression. Conversely, minocycline or IL
      1ra pretreatment increased GFAP expression as compared with that of control rats.
      However, i.t. pretreatment with fluorocitrate, an astrocyte inhibitor, restored
      minocycline- or IL-1ra-induced contralateral MA. These results suggest that
      spinal IL-1beta derived from activated microglia temporarily suppresses astrocyte
      activation, which can ultimately prevent the development of contralateral MA
      under inflammatory conditions. These findings imply that microglial IL-1beta
      plays an important role in regulating the induction of inflammatory MIP. 

PMID- 25749307
TI  - Synthesis and characterization of a trinuclear iridium(III) based catalyst for
      the photocatalytic reduction of CO2.
AB  - A trimetallic Ir(iii) based complex () was synthesized and fully characterized by
      spectroscopic and electrochemical methods. A detailed comparison to its mono- ()
      and bimetallic () analogue regarding the photocatalytic reduction of CO2 is
      outlined. In particular, the effect of intramolecular quenching, provided by
      ethyl tethers, was investigated. Moreover, the relationship between the
      photophysical properties, the lifetime of the excited state, the quenching
      efficiency and the catalytic performance is presented. Notably, the covalent
      linkage of the Ir(iii) moieties within the three-armed ligand structure (complex
      ) leads to a twofold increase of the turn over number (TON) compared to its
      monometallic analogue . Taking in account the quantum efficiency of 10% and the
      TONCO = 60 (per Ir(iii) center), complex is a highly active Ir(iii) based
      photocatalyst. 

PMID- 25749306
TI  - Combination of morphine with nortriptyline for neuropathic pain.
AB  - First-line neuropathic pain drugs, including tricyclic antidepressants, are not
      always effective, and opioids have been recommended as second line. This trial
      evaluates a nortriptyline-morphine combination, compared with each monotherapy.
      In this randomized, double-blind crossover trial, patients with neuropathic pain
      were enrolled at 1 site between January 25, 2010, and May 22, 2014, and
      randomized in a 1:1:1 ratio using a balanced Latin square design to receive oral
      nortriptyline, morphine, and their combination. During each of three 6-week
      periods, doses were titrated toward maximal tolerated dose (MTD). The primary
      outcome was average daily pain at MTD, and secondary outcomes included other
      pain, mood and quality of life measures, and adverse effects. Sixty-two patients
      were screened, 52 enrolled, and 39 completed at least 2 treatment periods.
      Average daily pain (0-10) at baseline was 5.3 and at MTD was 2.6 for combination
      vs 3.1 for nortriptyline (P = 0.046) and 3.4 for morphine (P = 0.002). Brief Pain
      Inventory scores for average and present pain were also significantly lower for
      combination vs each monotherapy. Combination treatment resulted in moderate
      severe constipation in 43% vs 46% with morphine (P = 0.82) and 5% with
      nortriptyline (P < 0.0001). Combination treatment resulted in moderate-severe dry
      mouth in 58% vs 49% with nortriptyline (P = 0.84) and 13% with morphine (P <
      0.0001). This trial suggests superior efficacy of a nortriptyline-morphine
      combination over either monotherapy with constipation, dry mouth, and somnolence
      as the most frequent adverse effects. 

PMID- 25749308
TI  - Controlled formation of emulsion gels stabilized by salted myofibrillar protein
      under malondialdehyde (MDA)-induced oxidative stress.
AB  - This study presented the cold-set gelation of emulsions stabilized by salted
      myofibrillar protein (MP) under oxidative stress originated from malondialdehyde
      (MDA). Gel properties were compared over a range of MDA/NaCl concentrations
      including gel viscoelastic properties, strength, water-holding capacity (WHC),
      amount of protein entrapped, and microstructure. The oxidative stability of
      emulsion gels as indicated by lipid hydroperoxide was further determined and
      compared. Results indicated that emulsion stabilized by MP at swollen state under
      certain ionic strengths (0.2-0.6 M) was the premise of gel formation under MDA.
      In the presence of intermediate MDA concentrations (2.5-10 mM), the emulsion gels
      showed an improved elasticity, strength, WHC, and oxidative stability. This
      improvement should be mainly attributed to the enhanced protein-protein cross
      linkings via MDA, which were homogeneously formed among absorbed and/or
      unabsorbed proteins, entrapping a greater amount and fractions of protein within
      network. Therefore, the oil droplets were better adherent to the gel matrix.
      Nevertheless, addition of high MDA concentrations (25-50 mM) led to the formation
      of excessive covalent bonds, which might break protein-protein bonds and trigger
      the desorption of protein from the interface. This ultimately caused "oil leak"
      phenomena as well as the collapse of gel structure and, thus, overall decreased
      gel properties and oxidative stability. 

PMID- 25749309
TI  - Beyond the border: effects of an expanding algal habitat on the fauna of
      neighbouring habitats.
AB  - The impacts of novel habitat-forming organisms on associated fauna have been
      difficult to predict, and may affect the fauna of neighbouring habitats due to
      changes in the spatial configuration of habitat patches of differing quality.
      Here, we test whether the localised expansion of a native habitat-forming
      macroalga, Caulerpa filiformis, on subtidal reefs can affect the abundance of
      fauna associated with a neighbouring macroalgal habitat. C. filiformis was a
      functionally distinct habitat for fauna, and the total abundance of epifauna
      associated with the resident alga, Sargassum linearifolium, was reduced at some
      sites when in close proximity to or surrounded by C. filiformis. Experimental
      manipulation of habitat configuration demonstrated that the low abundance of
      gastropods on S. linearifolium when surrounded by C. filiformis was likely
      explained by C. filiformis acting as a physical dispersal barrier for mobile
      fauna. Changes to the spatial configuration of novel and resident habitats can
      thus affect the abundance of fauna in addition to the direct replacement of
      habitats by species undergoing range expansions or increasing in abundance. 

PMID- 25749310
TI  - Design of a large outcome trial for a multivalent human papillomavirus L1 virus
      like particle vaccine.
AB  - BACKGROUND: The 9-valent human papillomavirus (HPV) (9vHPV) vaccine targets the
      four HPV types (6/11/16/18) covered by the licensed quadrivalent HPV (qHPV)
      vaccine and five additional types (31/33/45/52/58). A large outcome trial of
      9vHPV vaccine was conducted. METHODS: An active control (qHPV vaccine) was used
      because a placebo is not ethically acceptable. Since qHPV vaccine is (and 9vHPV
      vaccine was anticipated to be) highly efficacious against HPV 6/11/16/18, low
      incidence of HPV 6/11/16/18-associated disease was expected. Consequently, an
      efficacy comparison of 9vHPV versus qHPV vaccine for HPV 6/11/16/18 would have
      been prohibitively large in size. Moreover, no minimum antibody level predicting
      protection against infection or disease is defined for HPV vaccination. As an
      alternative approach, the two vaccines were compared using immunogenicity
      bridging for HPV 6/11/16/18 and clinical efficacy for HPV 31/33/45/52/58.
      RESULTS: The two co-primary objectives were to demonstrate: (1) non-inferior anti
      HPV 6/11/16/18 antibody response; and (2) superior efficacy in HPV 31/33/45/52/58
      related clinical outcome, for 9vHPV vaccine versus qHPV vaccine. For HPV
      6/11/16/18, supportive analyses included a non-inferiority assessment of the
      percent risk reduction (compared to historical placebo) for 9vHPV versus qHPV
      vaccine. CONCLUSIONS: A Phase III study of 9vHPV vaccine was successfully
      implemented. Experience from this study design may be applicable when developing
      a multivalent vaccine covering the same serotypes as an existing vaccine plus
      additional serotypes and there is no immune correlate of protection. Also, this
      study established that efficacy of a new HPV vaccine may be demonstrated using
      immunogenicity endpoints, which may open new options in HPV vaccine development.

PMID- 25749311
TI  - Statistical issues for design and analysis of single-arm multi-stage phase II
      cancer clinical trials.
AB  - BACKGROUND: Phase II trials have been very widely conducted and published every
      year for cancer clinical research. In spite of the fast progress in design and
      analysis methods, single-arm two-stage design is still the most popular for phase
      II cancer clinical trials. Because of their small sample sizes, statistical
      methods based on large sample approximation are not appropriate for design and
      analysis of phase II trials. METHODS: As a prospective clinical research, the
      analysis method of a phase II trial is predetermined at the design stage and it
      is analyzed during and at the end of the trial as planned by the design. The
      analysis method of a trial should be matched with the design method. For two
      stage single arm phase II trials, Simon's method has been the standards for
      choosing an optimal design, but the resulting data have been analyzed and
      published ignoring the two-stage design aspect with small sample sizes.
      CONCLUSIONS: In this article, we review analysis methods that exactly get along
      with the exact two-stage design method. We also discuss some statistical methods
      to improve the existing design and analysis methods for single-arm two-stage
      phase II trials.

PMID- 25749313
TI  - What did we learn from PEGASEAS forum "Science and Governance of the Channel
      Marine Ecosystem"?
AB  - As one of the busiest marine ecosystems in the world, the English Channel is
      subjected to strong pressures due to the human activities occurring within it.
      Effective governance is required to improve the combined management of different
      activities and so secure the benefits provided by the Channel ecosystem. In July
      2014, a Cross-Channel Forum, entitled "Science and Governance of the Channel
      Marine Ecosystem", was held in Caen (France) as part of the INTERREG project
      "Promoting Effective Governance of the Channel Ecosystem" (PEGASEAS). Here we use
      outputs from the Forum as a framework for providing Channel-specific advice and
      recommendations on marine governance themes, including the identification of
      knowledge gaps, which may form the foundation of future projects for the next
      INTERREG project call (2015-2020). 

PMID- 25749312
TI  - PROMIS--Prostate MR imaging study: A paired validating cohort study evaluating
      the role of multi-parametric MRI in men with clinical suspicion of prostate
      cancer.
AB  - BACKGROUND: Transrectal ultrasound-guided prostate biopsies are prone to
      detection errors. Multi-parametric MRI (MP-MRI) may improve the diagnostic
      pathway. METHODS: PROMIS is a prospective validating paired-cohort study that
      meets criteria for level 1 evidence in diagnostic test evaluation. PROMIS will
      investigate whether multi-parametric (MP)-MRI can discriminate between men with
      and without clinically-significant prostate cancer who are at risk prior to first
      biopsy. Up to 714 men will have MP-MRI (index), 10-12 core TRUS-biopsy (standard)
      and 5mm transperineal template mapping (TPM) biopsies (reference). The conduct
      and reporting of each test will be blinded to the others. RESULTS: PROMIS will
      measure and compare sensitivity, specificity, and positive and negative
      predictive values of both MP-MRI and TRUS-biopsy against TPM biopsies. The MP-MRI
      results will be used to determine the proportion of men who could safely avoid
      biopsy without compromising detection of clinically-significant cancers. For the
      primary outcome, significant cancer on TPM is defined as Gleason grade >/= 4+3
      and/or maximum cancer core length of >= 6 mm. PROMIS will also assess inter
      observer variability among radiologists among other secondary outcomes. Cost
      effectiveness of MP-MRI prior to biopsy will also be evaluated. CONCLUSIONS:
      PROMIS will determine whether MP-MRI of the prostate prior to first biopsy
      improves the detection accuracy of clinically-significant cancer.

PMID- 25749314
TI  - Rebuttal to published article "Review of oil spill remote sensing" by M. Fingas
      and C. Brown.

PMID- 25749315
TI  - Physiological perturbations in juvenile cuttlefish Sepia officinalis induced by
      subchronic exposure to dissolved zinc.
AB  - Although cephalopod early life stage development often occurs in coastal areas
      where contamination is real and continuous, the physiological perturbations
      induced by contaminants have been rarely investigated. This study focused on the
      Zn as it is one of the trace metals the most concentrated in coastal waters,
      worldwide. As Zn-tolerance limits were unknown in juvenile Sepia officinalis, the
      aim of this study was to estimate the threshold inducing mortality during the 2
      first weeks post-hatching, and to determine its sensitivity using digestive and
      immune enzymatic assays, as well as growth and behavior follow-up during the
      first 5weeks post-hatching. Our study highlighted a Zn-mortality threshold lying
      between 185 and 230MUgl(-1), and growth reductions occurring after 5-week at
      108MUgl(-1) and above, associated with enzymatic perturbations. These results
      underline a relatively important sensitivity of juvenile cuttlefish to Zn,
      pointed out by a wide diversity of biomarkers. 

PMID- 25749316
TI  - Debris ingestion by juvenile marine turtles: an underestimated problem.
AB  - Marine turtles are an iconic group of endangered animals threatened by debris
      ingestion. However, key aspects related to debris ingestion are still poorly
      known, including its effects on mortality and the original use of the ingested
      debris. Therefore, we analysed the impact of debris ingestion in 265 green
      turtles (Chelonia mydas) over a large geographical area and different habitats
      along the Brazilian coast. We determined the death rate due to debris ingestion
      and quantified the amount of debris that is sufficient to cause the death of
      juvenile green turtles. Additionally, we investigated the original use of the
      ingested debris. We found that a surprisingly small amount of debris was
      sufficient to block the digestive tract and cause death. We suggested that debris
      ingestion has a high death potential that may be masked by other causes of death.
      An expressive part of the ingested debris come from disposable and short-lived
      products. 

PMID- 25749317
TI  - Hypertension and the fat-soluble vitamins A, D and E.
AB  - Hypertension affects populations globally and is thus a public health and socio
      economic problem. Macronutrient and micronutrient deficiencies are common in the
      general population, and may be even more prevalent in hypertensive patients. This
      study aimed to determine a possible association between hypertension and intake
      of fat-soluble vitamins A, D and E. Participants were from the cross-sectional
      Hortega nutrition study conducted with a random sample of 1514 people (50.3%
      women, 49.7% men) and two groups: nonhypertensive controls>=40 years old (n=429;
      28.3%); unknown untreated hypertension cases>=40 years old (n=246; 16.2%).
      Biochemical and anthropometric measurements were taken. Data on dietary intakes,
      education, socio-economic status, place of residence, health habits,
      comorbidities, alcohol consumption and smoking were collected and assessed. A
      descriptive data study was done and compared by ANOVA and Chi-Square. No p value
      higher than 0.05 was considered significant. The results showed that vitamin A
      intake was higher in the hypertensive subpopulation (1732.77+/-962.27 ug vs.
      1655.89+/-902.81 ug), and vitamin D and E intakes were lower (8.13+/-9.71 ug vs.
      8.25+/-9.52 ug and 18.79+/-7.84 mg vs. 18.60+/-8.20 mg, respectively). No
      statistically significant differences were found in any adjusted model. This
      study did not significantly associate intake of vitamins A, D and E with
      hypertension in people aged over 40. Future studies on this topic and a larger
      sample are necessary.

PMID- 25749318
TI  - Ensuring healthy American Indian generations for tomorrow through safe and
      healthy indoor environments.
AB  - American Indians (AI) have the highest rate of severe physical housing problems
      in the U.S. (3.9%). Little information exists about the environmental hazards in
      AI homes. The purposes of this paper are to discuss challenges that were
      encountered when recruiting AI for a home-and employment-based environmental
      health assessments, highlight major successes, and propose recommendations for
      future indoor environmental health studies. The Center for American Indian
      Community Health (CAICH) and Children's Mercy Hospital's Center for Environmental
      Health and Allergy and Immunology Research Lab collaborated to provide
      educational sessions and healthy home assessments for AI. Through educational
      trainings, more than 240 AI were trained on the primary causes of health problems
      in homes. A total of 72 homes and places of employment were assessed by AI
      environmental health specialists. The top three categories with the most concerns
      observed in the homes/places of employment were allergens/dust (98%),
      safety/injury (89%) and chemical exposure (82%). While some information on
      smoking inside the home was collected, these numbers may have been underreported
      due to stigma. This was CAICH's first endeavor in environmental health and
      although challenges arose, many more successes were achieved. 

PMID- 25749319
TI  - Changes in socioeconomic inequalities in the use of dental care following major
      healthcare reform in Chile, 2004-2009.
AB  - The study examines changes in the distribution and socioeconomic inequalities of
      dental care utilization among adults after the major healthcare reform in Chile,
      2004-2009. We evaluated the proportion of people who visited the dentist at least
      once in the previous two years, and the mean number of visits. These outcome
      variables were stratified by sex, age (20-39, 40-59, 60-63; >=64 years),
      educational level (primary, secondary, higher), type of health insurance (public,
      private, uninsured), and socioeconomic status (quintiles of an asset-index). We
      also used the concentration index (CIndex) to assess the extent of socioeconomic
      inequalities in the use of dental care, stratified by age and sex as a proxy for
      dental care needs. The use of dental care significantly increased between 2004
      and 2009, especially in those with public health insurance, with lower
      educational level and lower socioeconomic status. The CIndex for the total
      population significantly decreased both for the proportion who used dental care,
      and also the mean number of visits. Findings suggest that the use of dental care
      increased and socioeconomic-related inequalities in the utilization of dental
      care declined after a Major Health Reform, which included universal coverage for
      some dental cares in Chile. However, efforts to ameliorate these inequalities
      require an approach that moves beyond a sole focus on rectifying health coverage.

PMID- 25749320
TI  - Future premature mortality due to O3, secondary inorganic aerosols and primary PM
      in Europe--sensitivity to changes in climate, anthropogenic emissions, population
      and building stock.
AB  - Air pollution is an important environmental factor associated with health impacts
      in Europe and considerable resources are used to reduce exposure to air pollution
      through emission reductions. These reductions will have non-linear effects on
      exposure due, e.g., to interactions between climate and atmospheric chemistry. By
      using an integrated assessment model, we quantify the effect of changes in
      climate, emissions and population demography on exposure and health impacts in
      Europe. The sensitivity to the changes is assessed by investigating the
      differences between the decades 2000-2009, 2050-2059 and 2080-2089. We focus on
      the number of premature deaths related to atmospheric ozone, Secondary Inorganic
      Aerosols and primary PM. For the Nordic region we furthermore include a
      projection on how population exposure might develop due to changes in building
      stock with increased energy efficiency. Reductions in emissions cause a large
      significant decrease in mortality, while climate effects on chemistry and
      emissions only affects premature mortality by a few percent. Changes in
      population demography lead to a larger relative increase in chronic mortality
      than the relative increase in population. Finally, the projected changes in
      building stock and infiltration rates in the Nordic indicate that this factor may
      be very important for assessments of population exposure in the future. 

PMID- 25749321
TI  - Mycobacteria in water used for personal hygiene in heavy industry and collieries:
      a potential risk for employees.
AB  - Environmental mycobacteria (EM) constitute a health risk, particularly for
      immunocompromised people. Workers in heavy industry and in collieries represent
      an at-risk group of people as their immunity is often weakened by long-term
      employment in dusty environments, frequent smoking and an increased occurrence of
      pulmonary diseases. This study was concerned with the presence of EM in non
      drinking water used for the hygiene of employees in six large industrial
      companies and collieries. Over a period of ten years, 1096 samples of surface
      water treated for hygiene purposes (treated surface water) and treated surface
      water diluted with mining water were examined. EM were detected in 63.4 and 41.5%
      samples of treated surface water and treated surface water diluted with mining
      water, respectively. Mycobacterium gordonae, M. avium-intracellulare and M.
      kansasii were the most frequently detected species. Adoption of suitable
      precautions should be enforced to reduce the incidence of mycobacteria in shower
      water and to decrease the infectious pressure on employees belonging to an at
      risk group of people. 

PMID- 25749322
TI  - Cadmium modulates biofilm formation by Staphylococcus epidermidis.
AB  - The aim of the study was to evaluate the effect of cadmium exposure on
      Staphylococcus epidermidis (ATCC 35984) biofilm formation. Bacteria were cultured
      in the absence or presence of different concentrations (0-50 uM) of cadmium.
      Biofilm formation and bacterial viability were assessed. Quantitative Real Time
      PCR (qRT-PCR) was used to determine the mRNA expression of molecular markers of
      S. epidermidis biofilm formation and dispersion. S. epidermidis biofilm formation
      was stimulated (p<0.001) by 1.56 and 3.13 uM cadmium. Confocal laser scanning
      microscopy (CLSM) analysis confirmed an increase in biofilm thickness (23 and 22
      um, versus 17.8 um in the controls) after exposure to 1.56 or 3.13 uM cadmium,
      respectively. qRT-PCR was performed showing the up-regulation of atlE, embp, aap,
      icaA and icaB after exposure to 3.13 uM cadmium. Taken together, these findings
      show that cadmium at low, sub-toxic concentrations acts as inducer of S.
      epidermidis biofilm formation.

PMID- 25749323
TI  - Influence of commonly used primer systems on automated ribosomal intergenic
      spacer analysis of bacterial communities in environmental samples.
AB  - Due to the high diversity of bacteria in many ecosystems, their slow generation
      times, specific but mostly unknown nutrient requirements and syntrophic
      interactions, isolation based approaches in microbial ecology mostly fail to
      describe microbial community structure. Thus, cultivation independent techniques,
      which rely on directly extracted nucleic acids from the environment, are a well
      used alternative. For example, bacterial automated ribosomal intergenic spacer
      analysis (B-ARISA) is one of the widely used methods for fingerprinting bacterial
      communities after PCR-based amplification of selected regions of the operon
      coding for rRNA genes using community DNA. However, B-ARISA alone does not
      provide any taxonomic information and the results may be severely biased in
      relation to the primer set selection. Furthermore, amplified DNA stemming from
      mitochondrial or chloroplast templates might strongly bias the obtained
      fingerprints. In this study, we determined the applicability of three different B
      ARISA primer sets to the study of bacterial communities. The results from in
      silico analysis harnessing publicly available sequence databases showed that all
      three primer sets tested are specific to bacteria but only two primers sets
      assure high bacterial taxa coverage (1406f/23Sr and ITSF/ITSReub). Considering
      the study of bacteria in a plant interface, the primer set ITSF/ITSReub was found
      to amplify (in silico) sequences of some important crop species such as Sorghum
      bicolor and Zea mays. Bacterial genera and plant species potentially amplified by
      different primer sets are given. These data were confirmed when DNA extracted
      from soil and plant samples were analyzed. The presented information could be
      useful when interpreting existing B-ARISA results and planning B-ARISA
      experiments, especially when plant DNA can be expected. 

PMID- 25749324
TI  - Natural antifouling compounds: Effectiveness in preventing invertebrate
      settlement and adhesion.
AB  - Biofouling represents a major economic issue regarding maritime industries and
      also raise important environmental concern. International legislation is
      restricting the use of biocidal-based antifouling (AF) coatings, and increasing
      efforts have been applied in the search for environmentally friendly AF agents. A
      wide diversity of natural AF compounds has been described for their ability to
      inhibit the settlement of macrofouling species. However poor information on the
      specific AF targets was available before the application of different molecular
      approaches both on invertebrate settlement strategies and bioadhesive
      characterization and also on the mechanistic effects of natural AF compounds.
      This review focuses on the relevant information about the main invertebrate
      macrofouler species settlement and bioadhesive mechanisms, which might help in
      the understanding of the reported effects, attributed to effective and non-toxic
      natural AF compounds towards this macrofouling species. It also aims to
      contribute to the elucidation of promising biotechnological strategies in the
      development of natural effective environmentally friendly AF paints. 

PMID- 25749325
TI  - [Development of a staging classification for leisure activities and social
      communication in dependent elderly persons].
AB  - AIM: The aim of this study was to develop a simple staging classification to
      measure leisure activity and social communication among the elderly at geriatric
      health care facilities. METHODS: In order to construct a staging scale for
      measuring the participation of the elderly subjects, we developed a list of 28
      items for three domains: leisure activities, social participation and
      communication. Data were obtained from users of institutional and day care
      services at geriatric health service facilities. The Rasch model was applied to
      test the degree of item fit and difficulty. Simple staging scales were
      constructed based on 12 leisure activity and nine social communication items. The
      validity and reliability were tested using these newly developed scales according
      to the Rasch model and assessments of the test-retest reliability. RESULTS: The
      participants were 3,458 elderly persons, of whom 1,560 were currently using
      institutional services and 1,898 were using day care services. Among the 28
      items, "traveling" was identified as the most difficult and "watching television"
      was identified as the easiest. Because items related to "social participation,"
      such as volunteer activities, exhibited a low frequency, they were not used in
      the further analyses. Simple staging scales were constructed by analyzing the
      remaining items of leisure activities and social communication according to the
      Rasch model. The thresholds within the scales were determined in order of item
      difficulty. Cohen's kappa, as assessed by two different evaluators, was 0.75 for
      leisure activities and 0.77 for social communication. CONCLUSIONS: In this study,
      we developed staging scales for leisure activity and social communication. The
      construct validity and test-retest reliability were adequate for both scales.
      Service providers can improve service quality by using these scales for
      individual case management of elderly persons in conjunction with existing scales
      of activities of daily living.

PMID- 25749326
TI  - [Factors associated with malnutrition in community-dwelling disabled elderly--the
      KANAGAWA-AICHI Disabled Elderly Cohort (KAIDEC) Study].
AB  - AIM: This study aimed to identify factors associated with malnutrition in
      community-dwelling disabled elderly. METHODS: A cross-sectional study of baseline
      data for 1,142 community-dwelling elderly (81.2+/-8.7 years) from of the KANAGAWA
      AICHI Disabled Elderly Cohort (KAIDEC) study was conducted. The data included the
      participants' demographic characteristics, nutritional status (Mini Nutritional
      Assessment short-form: MNA-SF), dysphagia status (Dysphagia Severity scale: DSS),
      comorbidity, basic activities of daily living (bADL), hospitalization with in the
      past three months and care level according to the Long-Term Care Insurance
      program. The participants were considered to be in malnutrition or at risk of
      malnutrition if their MNA-SF score was 0-7 or 8-11, respectively. The chi square
      test, analysis of variance, Jonckheere-Terpstra trend test and logistic
      regression analysis were used for the statistical analysis. RESULTS: A total of
      16.7% of the participants were classified as having malnutrition. In addition, a
      higher prevalence of malnutrition was associated with a higher care level in the
      long-term care insurance program, and malnutrition was associated with a lower
      bADL score, the presence of dysphagia and dementia and hospitalization with in
      the past three months. CONCLUSIONS: The present study demonstrated that
      malnutrition in community-dwelling disabled elderly is associated with a lower
      bADL score, the presence of dysphagia and dementia and hospitalization with in
      the past three months.

PMID- 25749327
TI  - [Examination of cases of pseudogout in succession to inflammatory disease in the
      elderly].
AB  - AIM: Pseudogout is an important causative disease of febrile illness in elderly
      patients. We experienced cases of pseudogout during or after the progression of
      inflammatory disease. METHODS: We investigated 14 patients with pseudogout
      admitted to the Department of Geriatric Medicine at Kyorin University Hospital.
      Seven patients who developed inflammatory disease prior to the onset of
      pseudogout are described in greater detail. RESULTS: The affected joint was the
      knee joint in 12 of 14 cases. Other joints were affected in four cases, and four
      patients had more than two affected joints in this series. Clear joint cartilage
      calcification was noted on X-rays in nine of 14 cases, and CPPD crystals were
      detected in two patients treated with joint puncture. NSAIDs were administered in
      all cases for treatment. Seven patients had a preceding inflammatory disease,
      with infectious disease in all cases. Repeat elevation of temperature and
      inflammatory reactions were seen in seven cases, with progression to bimodal
      disease in two cases. The average duration of antimicrobial use was 11 days. In
      three cases, the average duration of antimicrobial use was 33 days, and two or
      more antimicrobials were used for long-term treatment. CONCLUSIONS: Pseudogout
      appears as delayed infective disease and fever of unknown origin in the elderly.
      This condition may easily be overlooked until joint symptoms become apparent. It
      is extremely important to keep pseudogout in mind as a differential diagnosis of
      thermogenesis in elderly patients.

PMID- 25749328
TI  - [A case of an elderly woman with dementia in whom nutrition via gastrostomy was
      discontinued after considerable discussion according to the guidelines].
AB  - A 94-year-old woman with Alzheimer's disease had been receiving nourishment via
      gastrostomy for three years and in a state in which communication was not
      possible. Upon the family's request for consultation and advice, and after a
      considerable discussion according to the guidelines, the decision was made to
      stop the gastrostomy feeding. The patient subsequently coincidentally contracted
      influenza one week later and died due to pneumonia. Based on our experience of
      making the decision to stop nutritional supplementation via gastrostomy according
      to the guidelines, there are various issues, such as the psychological distress
      of the family, which cannot be resolved based on the guidelines. 

PMID- 25749329
TI  - [A case of renal spindle cell carcinoma].
AB  - An asymptomatic 67-year-old woman was found to have renal tumors by chance on a
      screening abdominal ultrasound examination. Although surgical resection was
      planned for both a diagnostic purposes and treatment, she suddenly developed
      hemorrhage from the cerebral metastasis in the left thalamus, and the surgical
      procedure was postponed. Irradiation with a gamma knife was performed to treat
      the cerebral metastasis; however, the patient's general condition quickly
      worsened, and she died six months after diagnosis. An autopsy showed typical
      spindle cells in the primary lesion with multiple metastases. Renal spindle cell
      carcinoma is a relatively rare type of the renal carcinoma that is both very
      aggressive and exhibits a poor prognosis, with few established treatments. Hence,
      obtaining an early diagnosis on abdominal ultrasound is important in such cases. 

PMID- 25749330
TI  - [Successful treatment with rituximab in a patient with splenic marginal zone B
      cell lymphoma accompanied by cold agglutinin disease].
AB  - An 81-year-old man was admitted to our hospital due to dyspnea in July 2008. A
      physical examination revealed marked splenomegaly, and the results of laboratory
      tests were as follows: hemoglobin (Hb)=7.0 g/dL, Ret=6.4%, WBC=24,100/MUL (Ly:
      20,003/MUL), indirect bilirubin=3.6 mg/dL, LDH=232 IU/L. The cold agglutinin
      titer was 1 : 8,192, and a direct antiglobulin test was positive. A PET scan
      showed abnormal accumulation in the spleen and bone marrow. A bone marrow
      aspirate examination and biopsy demonstrated diffuse involvement of abnormal
      lymphocytes that were found to be positive for CD20 and negative for CD5, CD10,
      and cyclin D1. The immunoglobulin genes were clonally rearranged. Based on these
      findings, splenic marginal zone B-cell lymphoma (SMZL) associated with cold
      agglutinin disease (CAD) was diagnosed. Because the patient refused splenectomy,
      he was treated with four cycles of rituximab therapy (375 mg/kg, once a week).
      The Hb level and lymphocyte count subsequently normalized and the splenomegaly
      resolved. One year later, he relapsed and was again treated with rituximab
      therapy with complete remission. CAD accompanied by SMZL is very rare. Rituximab
      may be chosen as an alternative and effective therapeutic option in patients with
      SMZL-particularly those with autoimmune hemolytic anemia. 

PMID- 25749331
TI  - [HIV-associated nephropathy with amoebic enteritis: a case report and literature
      review].
AB  - We herein describe a case of HIV-associated nephropathy (HIVAN) in a 64-year-old
      HIV antibody-positive man presenting with proteinuria. Laboratory examinations
      showed positive proteinuria, a high beta2-microglobulin level and decreased
      creatinine clearance. He underwent a percutaneous renal biopsy, and a pathologic
      evaluation revealed a collapsing form of focal sclerosing glomerulosclerosis.
      Histologically, HIVAN is a collapsing form of focal sclerosing glomerulosclerosis
      (FSGS), which can be distinguished from idiopathic FSGS by the presence of
      microcystic tubular dilatation and interstitial inflammation. The patient was
      diagnosed with HIV-associated nephropathy and was started on ART. The HIV
      associated nephropathy did not progress to acute renal failure, and long-term
      survival has been observed for over 12 years. 

PMID- 25749332
TI  - [Acyclovir-induced neurotoxicity and acute kidney injury in an elderly diabetic
      patient treated with valacyclovir: report of a case].
AB  - An 83-year-old Japanese man had a 29-year history of well-controlled diabetes
      mellitus. His HbA1c level was approximately 6.0%, with no microalbuminuria and a
      serum creatinine level seven days before admission of 0.8 mg/dl (eGFR: 69.67
      ml/min/1.73 m(2)). Five days before admission, he visited an ophthalmologist with
      inflammation of the right palpebra and conjunctiva and began taking valacyclovir
      at a dose of 3,000 mg for the treatment of herpes zoster. Two days before
      admission, he was prescribed loxoprofen at a dose of 180 mg for a headache. One
      day prior to admission, he developed dysarthria, wandering and loss of appetite.
      He was subsequently admitted to our hospital with progressive deterioration of
      consciousness (Japan Coma Scale: II-20). On admission, he exhibited renal
      dysfunction, with a serum creatinine level of 5.11 mg/dl (eGFR: 9.16 ml/min/1.73
      m(2)). Based on his diverse symptoms and current treatment with valacyclovir, the
      patient was diagnosed with acyclovir-induced neurotoxicity and his symptoms
      rapidly improved after hemodialysis. The serum acyclovir level on admission was
      found to be 9.25 MUg/ml. Although acyclovir-induced neurotoxicity is commonly
      seen in elderly patients with renal dysfunction, there are also reports of this
      condition in patients with a normal renal function. Valacyclovir is frequently
      prescribed to the elderly to treat diseases such as herpes zoster. As
      valacyclovir induces renal dysfunction, which raises the serum acyclovir level to
      the toxic range, special attention must be paid when administering this drug in
      elderly subjects. 

PMID- 25749333
TI  - [Tuberculosis of the thyroid gland mimicking thyroid carcinoma in the elderly].
AB  - A 76-year-old woman with a 10-year history of chronic glomerulonephritis was
      treated at a clinic after presenting with a gradual worsening of the renal
      function. The patient had no history of tuberculosis. She was subsequently
      hospitalized for uremic symptoms and treated with internal shunt insertion and
      dialysis. Thyroid ultrasonography was performed to screen for secondary
      hyperparathyroidism, which revealed a calcified thyroid mass and cervical lymph
      node swelling. Fine-needle aspiration biopsy was thus conducted to assess
      suspected thyroid cancer. The cytological findings showed few follicular
      epithelial cells, without any signs of malignancy. However, a diagnosis of
      thyroid cancer continued to be strongly suspected based on the imaging features.
      Total thyroidectomy and bilateral cervical regional lymph node dissection were
      therefore performed, and the pathological examination of the thyroidectomy
      specimen disclosed scattered epithelioid granulomas with caseous necrosis in the
      entire right lobe as well as the cervical lymph nodes. Based on these findings,
      the patient was diagnosed with thyroid tuberculosis. As the symptoms and imaging
      findings of tuberculosis are nonspecific in elderly patients, it is necessary to
      consider this disease in this population. We therefore propose the inclusion of
      thyroid tuberculosis in the differential diagnosis of elderly patients who
      present with malignant thyroid tumors on aspiration biopsy cytology, regardless
      of whether or not they have a previous history of tuberculosis. 

PMID- 25749337
TI  - Caloric restriction mimetic 2-deoxyglucose alleviated lethal liver injury induced
      by lipopolysaccharide/D-galactosamine in mice.
AB  - The glycolytic inhibitor 2-deoxyglucose (2-DG) is a calorie restriction (CR)
      mimetic produces CR-like beneficial effects in both acute and chronic
      pathological processes, but whether 2-DG is also helpful in critical and life
      threatening situation is not known. In the present study, the potential benefits
      of 2-DG in lipopolysaccharide/D-galactosamine (LPS/D-Gal)-induced lethal liver
      injury were investigated. The results indicated that treatment with 2-DG
      suppressed the elevation of plasma aminotransferases, alleviated the
      histopathological abnormalities and improved the survival rate of LPS/D-Gal
      exposed mice. Treatment with 2-DG also suppressed the production of pro-apoptotic
      cytokine TNF-alpha, the phosphorylation of JNK, the activation of caspase cascade
      and the count of TUNEL-positive apoptotic hepatocytes. These data suggested that
      the CR mimetic 2-DG could also provide beneficial effects in lethal pathological
      process such as LPS/D-Gal-induced fulminant liver injury.

PMID- 25749338
TI  - TLR2 deficiency attenuates skeletal muscle atrophy in mice.
AB  - Oxidative stress and inflammation are associated with skeletal muscle atrophy.
      Because the activation of toll-like receptor (TLR) 2 induces oxidative stress and
      inflammation, TLR2 may be directly linked to skeletal muscle atrophy. This study
      examined the role of TLR2 in skeletal muscle atrophy in wild-type (WT) and TLR2
      knockout (KO) mice. Immobilization for 2 weeks increased the expression of
      cytokine genes and the levels of carbonylated proteins and nitrotyrosine in the
      skeletal muscle, but these increases were lower in the TLR2 KO mice. Muscle
      weight loss and a reduction in treadmill running times induced by immobilization
      were also attenuated in TLR2 KO mice. Furthermore, immobilization increased the
      protein levels of forkhead box O 1/3, atrogin-1 and muscle ring finger 1 in the
      WT mice, which was attenuated in TLR2 KO mice. In addition, immobilization
      associated increases in ubiquitinated protein levels were lower in the TLR2 KO
      mice. Immobilization increased the phosphorylation of Akt and p70S6K similarly in
      WT and KO mice. Furthermore, cardiotoxin injection into the skeletal muscle
      increased the protein levels of atrogin-1, interleukin-6, and nitrotyrosine and
      increased the levels of ubiquitinated proteins, although these levels were
      increased to a lesser extent in TLR2 KO mice. These results suggest that TLR2 is
      involved in skeletal muscle atrophy, and the inhibition of TLR2 offers a
      potential target for preventing skeletal muscle atrophy. 

PMID- 25749339
TI  - Osteopontin-induced brown adipogenesis from white preadipocytes through a PI3K
      AKT dependent signaling.
AB  - Recent studies have shown that OPN (osteopontin) plays critical roles in cell
      survival, differentiation, bio-mineralization, cancer and cardiovascular
      remodeling. However, its roles in the differentiation of brown adipocytes and the
      underlying mechanisms remain unclear. Therefore, the aim of this study was to
      investigate the roles of OPN in the brown adipogenesis and the underlying
      mechanisms. It was shown that the OPN successfully induced the differentiation of
      3T3-L1 white preadipocytes into the PRDM16(+) (PRD1-BF1-RIZ1 homologous domain
      containing 16) and UCP-1(+) (uncoupling protein-1) brown adipocytes in a
      concentration and time-dependent manner. Also, activation of PI3K
      (phosphatidylinositol 3-kinase)-AKT pathway was required for the OPN-induced
      brown adipogenesis. The findings suggest OPN plays an important role in promoting
      the differentiation of the brown adipocytes and might provide a potential novel
      therapeutic approach for the treatment of obesity and related disorders. 

PMID- 25749340
TI  - Tumor promotion by exposure to radiofrequency electromagnetic fields below
      exposure limits for humans.
AB  - The vast majority of in vitro and in vivo studies did not find cancerogenic
      effects of exposure to electromagnetic fields (RF-EMF), i.e. emitted by mobile
      phones and base stations. Previously published results from a pilot study with
      carcinogen-treated mice, however, suggested tumor-promoting effects of RF-EMF
      (Tillmann et al., 2010). We have performed a replication study using higher
      numbers of animals per group and including two additional exposure levels (0
      (sham), 0.04, 0.4 and 2 W/kg SAR). We could confirm and extend the originally
      reported findings. Numbers of tumors of the lungs and livers in exposed animals
      were significantly higher than in sham-exposed controls. In addition, lymphomas
      were also found to be significantly elevated by exposure. A clear dose-response
      effect is absent. We hypothesize that these tumor-promoting effects may be caused
      by metabolic changes due to exposure. Since many of the tumor-promoting effects
      in our study were seen at low to moderate exposure levels (0.04 and 0.4 W/kg
      SAR), thus well below exposure limits for the users of mobile phones, further
      studies are warranted to investigate the underlying mechanisms. Our findings may
      help to understand the repeatedly reported increased incidences of brain tumors
      in heavy users of mobile phones. 

PMID- 25749341
TI  - Increased sensitivity of apolipoprotein E knockout mice to copper-induced
      oxidative injury to the liver.
AB  - Apolipoprotein E (ApoE) genotypes are related to clinical presentations in
      patients with Wilson's disease, indicating that ApoE may play an important role
      in the disease. However, our understanding of the role of ApoE in Wilson's
      disease is limited. High copper concentration in Wilson's disease induces
      excessive generation of free oxygen radicals. Meanwhile, ApoE proteins possess
      antioxidant effects. We therefore determined whether copper-induced oxidative
      damage differ in the liver of wild-type and ApoE knockout (ApoE(-/-)) mice. Both
      wild-type and ApoE(-/-) mice were intragastrically administered with 0.2 mL of
      copper sulfate pentahydrate (200 mg/kg; a total dose of 4 mg/d) or the same
      volume of saline daily for 12 weeks, respectively. Copper and oxidative stress
      markers in the liver tissue and in the serum were assessed. Our results showed
      that, compared with the wild-type mice administered with copper, TBARS as a
      marker of lipid peroxidation, the expression of oxygenase-1 (HO-1), NAD(P)H
      dehydrogenase, and quinone 1 (NQO1) significantly increased in the ApoE(-/-) mice
      administered with copper, meanwhile superoxide dismutase (SOD) activity
      significantly decreased. Thus, it is concluded that ApoE may protect the liver
      from copper-induced oxidative damage in Wilson's disease.

PMID- 25749342
TI  - Chikusetsusaponin IVa methyl ester induces cell cycle arrest by the inhibition of
      nuclear translocation of beta-catenin in HCT116 cells.
AB  - We demonstrate that chikusetsusaponin IVa methyl ester (CME), a triterpenoid
      saponin from the root of Achyranthes japonica, has an anticancer activity. We
      investigate its molecular mechanism in depth in HCT116 cells. CME reduces the
      amount of beta-catenin in nucleus and inhibits the binding of beta-catenin to
      specific DNA sequences (TCF binding elements, TBE) in target gene promoters.
      Thus, CME appears to decrease the expression of cell cycle regulatory proteins
      such as Cyclin D1, as a representative target for beta-catenin, as well as CDK2
      and CDK4. As a result of the decrease of the cell cycle regulatory proteins, CME
      inhibits cell proliferation by arresting the cell cycle at the G0/G1 phase.
      Therefore, we suggest that CME as a novel Wnt/beta-catenin inhibitor can be a
      putative agent for the treatment of colorectal cancers. 

PMID- 25749343
TI  - 10-oxo-12(Z)-octadecenoic acid, a linoleic acid metabolite produced by gut lactic
      acid bacteria, potently activates PPARgamma and stimulates adipogenesis.
AB  - Our previous study has shown that gut lactic acid bacteria generate various kinds
      of fatty acids from polyunsaturated fatty acids such as linoleic acid (LA). In
      this study, we investigated the effects of LA and LA-derived fatty acids on the
      activation of peroxisome proliferator-activated receptors (PPARs) which regulate
      whole-body energy metabolism. None of the fatty acids activated PPARdelta,
      whereas almost all activated PPARalpha in luciferase assays. Two fatty acids
      potently activated PPARgamma, a master regulator of adipocyte differentiation,
      with 10-oxo-12(Z)-octadecenoic acid (KetoA) having the most potency. In 3T3-L1
      cells, KetoA induced adipocyte differentiation via the activation of PPARgamma,
      and increased adiponectin production and insulin-stimulated glucose uptake. These
      findings suggest that fatty acids, including KetoA, generated in gut by lactic
      acid bacteria may be involved in the regulation of host energy metabolism. 

PMID- 25749344
TI  - Optimization of anti-CD20 humanized antibody hu8E4 by site-directed mutation
      based on epitope analysis.
AB  - Despite the effectiveness of the anti-CD20 chimeric antibody (mAb), rituximab, in
      treating B-cell lymphomas, its efficacy remains variable and often modest. Hu8E4
      is an anti-CD20 humanized antibody which exhibits markedly higher antitumor
      activity compared with rituximab. Previous studies have indicated that rituximab
      and almost all known anti-CD20 murine mAbs recognize the A170/P172 motif within
      the large extracellular loop of CD20. In this study, we demonstrated that hu8E4
      also recognized the A170/P172 motif, suggesting that the epitopes recognized by
      rituximab and hu8E4 are very similar. Based on this, three single mutations
      (D57E, Y102K and Y102T) at the heavy chain variable region that can improve the
      affinity of rituximab were transferred to hu8E4. The results showed that D57E and
      Y102T but not Y102K successfully enhanced the binding of hu8E4 to CD20. Out of
      these hu8E4 mutants, hu8E4D57E exhibited the highest affinity. The in vitro and
      in vivo antitumor activity of hu8E4D57E was further investigated. Our data
      indicated that hu8E4D57E was as effective as hu8E4 in mediating CDC and inducing
      apoptosis in B-lymphoma cells, but it was more potent in ADCC than hu8E4.
      Importantly, hu8E4D57E was shown to be significantly more effective than Hu8E4 in
      prolonging the survival of SCID mice bearing disseminated B-lymphoma cells,
      suggesting that it might be a promising therapeutic agent for B-cell lymphomas.
      Moreover, this study also suggests that the mutations that can improve the
      affinity of rituximab may be transferred to other anti-CD20 murine mAbs to
      enhance their binding to CD20. 

PMID- 25749345
TI  - Crystal structure and biochemical properties of ReH16_A1887, the 3-ketoacyl-CoA
      thiolase from Ralstonia eutropha H16.
AB  - ReH16_A1887 from Ralstonia eutropha is an enzyme annotated as a 3-ketoacyl-CoA
      thiolase, and it catalyzes the fourth step of beta-oxidation degradative pathways
      by converting 3-ketoacyl-CoA to acyl-CoA. We determined the crystal structures of
      ReH16_A1887 in the apo-form and in complex with its CoA substrate. ReH16_A1887
      functions as a dimer, and the monomer of ReH16_A1887 comprises three subdomains
      (I, II, and III). The structural comparison between the apo-form and the CoA
      bound form revealed that ReH16_A1887 undergoes a structural change in the lid
      subdomain (subdomain III) upon the binding of the CoA substrate. The CoA molecule
      was stabilized by hydrogen bonding with positively charged residues such as
      Lys18, Arg210, and Arg217, and residues Thr213 and Gln151 aid its binding as
      well. At the active site of ReH16_A1887, highly conserved residues such as Cys91,
      His348, and Cys378 were located near the thiol-group of CoA, indicating that
      ReH16_A1887 might catalyze the thiolase reaction in a way similar to other
      thiolases. Moreover, in the vicinity of the covalent nucleophile Cys91, a
      hydrophobic hole that might serve as a binding site for the acyl-group of 3
      ketoacyl-CoA was observed. The residues involved in enzyme catalysis and
      substrate-binding were further confirmed by site-directed mutagenesis
      experiments. 

PMID- 25749346
TI  - Minimal important difference of the 6-minute walk distance in lung cancer.
AB  - The 6-minute walk distance (6MWD) is one of the most commonly used measures of
      functional capacity in lung cancer, however, the minimal important difference
      (MID) has not been established. The aims of this exploratory study are, in lung
      cancer, to estimate (1) the MID of the 6MWD and (2) relationship between 6MWD,
      demographic and disease-related factors. Fifty-six participants with stage I-IV
      lung cancer completed the 6MWD prior to treatment and 10 weeks later. No exercise
      intervention occurred. Additional measures included European Organization for
      Research and Treatment of Cancer questionnaire (EORTC-QLQ-C30) and questionnaires
      assessing function, physical activity and symptoms. MID was calculated using
      anchor- and distribution-based methods. The mean 6MWD decline in participants
      classed as deteriorated was 60 m compared with 16 m in participants classed as
      not-deteriorated (p = 0.01). The receiver operating curve indicated a cut-off
      value for clinically relevant change to be 42 m (95% confidence interval (CI) 6
      75) (area under curve = 0.66, 95% CI 0.51-0.81) or a 9.5% change. Distribution
      based methods indicated an MID between 22 m (95% CI 18-26) and 32 m (95% CI 20
      42). Higher 6MWD correlated with better function (r = -0.42, p = 0.001), physical
      activity (r = 0.56, p < 0.005) and dyspnoea (r = -0.44, p = 0.001). The MID for
      deterioration of the 6MWD in lung cancer is estimated to be between 22 m and 42 m
      or a change of 9.5%. 

PMID- 25749347
TI  - Measuring fatigue as a symptom in COPD: From descriptors and questionnaires to
      the importance of the problem.
AB  - Fatigue is a symptom commonly diagnosed in cancers and in many other chronic
      debilitating diseases and is one of the main therapeutic targets for various
      pharmacologic and non-pharmacologic interventions. However, in chronic
      obstructive pulmonary disease (COPD), this symptom, which can be considered as
      the main extrapulmonary clinical feature of the disease, can impact significantly
      on the health-related quality of life of the patients. The aims of this review
      are to discuss the issues related to fatigue assessment in COPD and to highlight
      the importance of this symptom in this setting based on the data retrieved from
      articles published between 1987 through August 2014 available on MEDLINE
      database. Fatigue can be measured by various scales or questionnaires that are
      designed for generic purposes or for COPD-related purposes but is still
      underdiagnosed and undertreated. This is due to the fact that its clinical and
      prognostic relevance are not appropriately acknowledged. The early identification
      of fatigue clinical descriptors from patients' reports could help with better
      management of this symptom. 

PMID- 25749349
TI  - Dienogest in the treatment of endometriosis: systematic review.
AB  - PURPOSE: Endometriosis is a prevalent disease that affects 5-15 % of women of
      reproductive age. The aim of this study is to assess the effect of dienogest in
      the treatment of endometriosis. METHODS: The search was applied to electronic
      databases PubMed, Cochrane, EMBASE and Lilacs until September 2014, in a public
      tertiary hospital. We performed a systematic literature search of randomized
      trials comparing dienogest to other medical therapies in the treatment of
      endometriosis, as well as their references list, using the keywords "dienogest"
      and "endometriosis" by two independent authors. The data extraction were
      performed by two authors using predefined data fields. Nine randomized trials
      were included. Dienogest 2 mg/day was superior to placebo in reducing pelvic pain
      (27.4 versus 15.1 mm, P < 0.0001), with similar results to buserelin,
      leuprorelin, leuprolide acetate and triptorelin, in controlling symptoms
      associated with endometriosis. Dienogest 2 mg/day was effective in reducing
      endometriotic lesions (11.4 +/- 1.71-3.6 +/- 0.95, P < 0.001). The extended
      therapy with dienogest 2 mg/day also showed an improvement in pelvic pain after
      24-52 weeks (-22.5 +/- 32.1 and -28.4 +/- 29.9 mm, respectively) with tolerable
      side effects. CONCLUSION: Dienogest should be considered as an alternative for
      controlling symptoms related to endometriosis. Nevertheless, in this systematic
      review, no studies were found comparing dienogest with first-line therapy, such
      as progestins and estrogen-progestogen combinations, which are proved to be
      effective in the treatment of endometriosis, are less expensive, and also can be
      used for contraception.

PMID- 25749348
TI  - Reduced Hedonic Capacity/Approach Motivation Relates to Blunted Responsivity to
      Gain and Loss Feedback in Children.
AB  - Adolescents and adults with major depressive disorder or elevated depressive
      symptoms show reduced reward responses and tend to show enhanced responses to
      negative stimuli. However, reward-related behaviors and adaptive responses to
      negative feedback undergo dramatic changes across puberty. Thus, key questions
      remain regarding how altered incentive processing relates to depressive and
      anhedonic symptoms in prepubertal child populations. Twenty-four nonclinical
      prepubertal children 7-10 years of age (15 male; 16 Caucasian) completed two
      signal detection tasks that assessed behavioral responsivity to candy gain and
      loss feedback, respectively. These tasks were based on Pizzagalli's probabilistic
      reward task where asymmetric feedback leads to greater bias toward the more
      frequently rewarded response in more hedonic or nondepressed adults. We further
      modified the task to create a version where incorrect responses could result in
      losses from an original allotment of candy. Children and parents/guardians also
      completed individual difference questionnaires to assess the child's depressive
      symptoms, general affect, and hedonic capacity/approach motivation. Regressions
      indicated a relation between hedonic capacity/approach motivation (child self
      report) and response bias in both gain and loss tasks. No significant relations
      were observed between depressive (child self-report), internalizing (parent
      report), or externalizing symptoms (parent report) and bias in either the gain or
      loss task in this small sample. These results suggest that reduced hedonic
      capacity/approach motivation is associated with blunted responses to both gain
      and loss feedback in prepubertal children.

PMID- 25749350
TI  - Systematic search for rare variants in Finnish early-onset colorectal cancer
      patients.
AB  - The heritability of colorectal cancer (CRC) is incompletely understood, and the
      contribution of undiscovered rare variants may be important. In search of rare
      disease-causing variants, we exome sequenced 22 CRC patients who were diagnosed
      before the age of 40 years. Exome sequencing data from 95 familial CRC patients
      were available as a validation set. Cases with known CRC syndromes were excluded.
      All patients were from Finland, a country known for its genetically homogenous
      population. We searched for rare nonsynonymous variants with allele frequencies
      below 0.1% in 3,374 Finnish and 58,112 non-Finnish controls. In addition,
      homozygous and compound heterozygous variants were studied. No genes with rare
      loss-of-function variants were present in more than one early-onset CRC patient.
      Three genes (ADAMTS4, CYTL1, and SYNE1) harbored rare loss-of-function variants
      in both early-onset and familial CRC cases. Five genes with homozygous variants
      in early-onset CRC cases were found (MCTP2, ARHGAP12, ATM, DONSON, and ROS1),
      including one gene (MCTP2) with a homozygous splice site variant. All discovered
      homozygous variants were exclusive to one early-onset CRC case. Independent
      replication is required to associate the discovered variants with CRC. These
      findings, together with a lack of family history in 19 of 22 (86%) early-onset
      patients, suggest genetic heterogeneity in unexplained early-onset CRC patients,
      thus emphasizing the requirement for large sample sizes and careful study designs
      to elucidate the role of rare variants in CRC susceptibility.

PMID- 25749351
TI  - Rare occurrence of a STAT5B N642H mutation in adult T-cell acute lymphoblastic
      leukemia.

PMID- 25749352
TI  - Expression and localization of testis developmental related gene 1 (TDRG1) in
      human spermatozoa.
AB  - Testis-specific proteins, synthesized during spermatogenesis and spermiogenesis,
      are necessary for spermatid differentiation and/or for mature sperm function
      during fertilization. However, majority of these genes have neither been
      identified nor fully characterized. Testis developmental related gene 1 (TDRG1),
      a newly identified human testis-specific gene, encodes a 100-amino-acid protein
      without any characterized protein domains, and it may play a role in
      spermatogenesis. However, whether this human-specific protein is important for
      mature sperm function remains unclear. As an initial effort, in this study, we
      aimed to systematically investigate the expression and localization of TDRG1 in
      normal human spermatozoa. Thus, immunohistochemistry was used to analyze the
      distribution of TDRG1 in human testis. Reverse transcription-polymerase chain
      reaction, western blot analysis and indirect immunofluorescence were used to
      determine the expression and localization of TDRG1 in normal human spermatozoa.
      The immunohistochemistry results showed that the TDRG1 protein was expressed in
      spermatogenic cells in the seminiferous tubules of human testis. Interestingly,
      the TDRG1 was more abundant in spermatogenic cells at the late stages of
      spermatogenesis. The TDRG1 antibody specifically recognized an 11-kDa protein
      only in soluble extracts from normal human spermatozoa. Indirect
      immunofluorescence assays indicated that TDRG1 located in the midpiece, principal
      piece and flagellum of normal human spermatozoa. In conclusion, TDRG1 was found
      not only in spermatogonia, but also in spermatozoa. The localization of TDRG1 in
      human normal spermatozoa implies its potential regulatory role in sperm motility.

PMID- 25749353
TI  - The shaking palsy.

PMID- 25749354
TI  - Cardiovascular autonomic testing performed with a new integrated instrumental
      approach is useful in differentiating MSA-P from PD at an early stage.
AB  - OBJECTIVE: To evaluate whether a battery of cardiovascular autonomic tests
      (Ewing's battery, EB) performed with a new integrated instrumental approach is
      useful in differentiating multiple system atrophy with predominant parkinsonism
      (MSA-P) from Parkinson's disease (PD) at an early stage. METHODS: We
      retrospectively analyzed EB tests of all the patients (n = 99) with a
      parkinsonian syndrome referred to our clinic who performed EB during the first
      diagnostic workup and were subsequently evaluated at least once a year until a
      final diagnosis of MSA-P (n = 34) or PD (n = 65). Thirty-eight controls matched
      for age and sex were included. EB consisted of head-up tilt test (HUTT), Valsalva
      manoeuvre (VM), deep breathing, and sustained handgrip whose correct execution
      and results were checked and obtained automatically. Results were compared
      between groups. Discriminant analysis was performed to identify MSA-P or PD
      patients. RESULTS: Orthostatic hypotension was found in 22 MSA-P and 3 PD
      patients. Cardiovascular reflexes indices were significantly more affected in MSA
      P compared to PD and controls. EB presented a 91% sensitivity and 94% specificity
      in the differentiation of MSA-P and PD. HUTT + VM presented a 91% sensitivity and
      92% specificity. CONCLUSIONS: Our results suggest that EB or HUTT + VM performed
      with an integrated instrumental approach and analyzed with the discriminant
      procedure may distinguish MSA-P from PD at an early stage and might improve the
      accuracy of current diagnostic criteria. However, a validation in separate
      samples and prospective studies is needed.

PMID- 25749356
TI  - Correction: A modified chronic infection model for testing treatment of
      Staphylococcus aureus biofilms on implants.

PMID- 25749355
TI  - Side of motor onset is associated with hemisphere-specific memory decline and
      lateralized gray matter loss in Parkinson's disease.
AB  - BACKGROUND: Parkinson's disease (PD) is a neurodegenerative disorder that
      generally begins with asymmetric motor symptoms that persist over time. This
      suggests that the dysfunction in the nigrostriatal motor circuit may be
      lateralized. The present study examined whether the asymmetric motor presentation
      is associated with hemisphere-specific cognitive decline and lateralized gray
      matter volume loss. METHODS: Data from comprehensive cognitive tests that
      measured visuospatial and verbal functions and high-resolution T1-weighted
      magnetic resonance images of the brain were acquired in 23 PD subjects with left
      side motor symptom onset (PDL), 23 PD subjects with right-side onset (PDR), and
      23 matched Controls. GM volume differences were assessed using voxel-based
      morphometry (VBM). Cognitive results and VBM were compared among the three
      groups, and correlation analyses were performed between those cognitive domains
      and brain areas that showed significant differences. RESULTS: PDL subjects had
      lower performance on visuospatial memory tasks compared to PDR. Furthermore, PDL
      subjects experienced lateralized GM loss, which was localized predominantly in
      the right hemisphere contralateral to the side of motor symptom onset.
      Visuospatial memory performance in PDL was correlated with GM loss in the right
      middle frontal gyrus and precuneus. CONCLUSION: These data suggest that the onset
      of asymmetric motor symptoms in PD may be associated with hemisphere-specific
      memory decline and lateralized GM loss, particularly in PDL. This study
      underscores the importance of classifying PD subgroups based on the side of motor
      symptom onset for clinical care and research to optimize cognitive outcomes.

PMID- 25749357
TI  - Pharmacological stimulation of metabotropic glutamate receptor type 4 in a rat
      model of Parkinson's disease and L-DOPA-induced dyskinesia: Comparison between a
      positive allosteric modulator and an orthosteric agonist.
AB  - Metabotropic glutamate receptor 4 (mGlu4) negatively modulates GABA and glutamate
      release in the 'indirect pathway' of the basal ganglia, and has thus been
      proposed as a potential target to treat motor symptoms in Parkinson's disease.
      Here, we present an extensive comparison of the behavioural effects produced by
      the mGlu4 positive allosteric modulator (PAM), VU0364770, and the mGlu4
      orthosteric agonist, LSP1-2111, in rats with unilateral 6-OHDA lesions. The
      compounds' activity was initially assessed in a test of haloperidol-induced
      catalepsy in intact rats, and effective doses were then evaluated in the
      hemiparkinsonian animal model. Neither of the two compounds modified the
      development of dyskinetic behaviours elicited by chronic treatment with full
      doses of l-DOPA. When given together with l-DOPA to rats with already established
      dyskinesias, neither VU0364770 nor LSP1-2111 modified the abnormal involuntary
      movement scores. VU0364770 potentiated, however, the motor stimulant effect of a
      subthreshold l-DOPA dose in certain behavioural tests, whereas LSP1-2111 lacked
      this ability. Taken together, these results indicate that a pharmacological
      stimulation of mGlu4 lacks intrinsic antidyskinetic activity, but may have DOPA
      sparing activity in Parkinson's disease. For the latter indication, mGlu4 PAMs
      appear to provide a better option than orthosteric agonists.

PMID- 25749358
TI  - Extinction and reinstatement to cocaine-associated cues in male and female
      juvenile rats and the role of D1 dopamine receptor.
AB  - Extinction of behaviors in response to drug-associated cues and prevention of
      reinstatement are integral for addiction treatment, and can reverse or ameliorate
      the harmful consequences of drug use. The mechanisms controlling extinction and
      reinstatement involve prefrontal cortical dopamine receptors, which change in
      expression and activity during the juvenile and adolescent transitions until they
      mature in adulthood. Little is known about the role that PFC D1 dopamine
      receptors play in extinction of drug-paired associations early in life. We used
      extinction of place preferences for cocaine in juvenile male and female rats
      following genetic, cell-specific overexpression of D1 on glutamatergic cells in
      the PFC. All subjects needed to demonstrate cocaine preferences for inclusion in
      the extinction studies. Here, male juveniles with a preference to 10 mg/kg
      cocaine took longer to extinguish preferences compared to both male adults and
      female juveniles. Female juveniles extinguished more rapidly than male juveniles
      at 20 mg/kg cocaine. Overexpression of D1 in juvenile males significantly
      facilitated extinction relative to juvenile male controls, whereas D1 prolonged
      expression of extinction in adults overexpressing D1 and adolescents who
      naturally have elevated D1 expression. These data suggest that an immature D1
      profile in juveniles prevented the learning of new associations, and D1
      overexpression may provide sufficient activity to facilitate extinction learning.
      D1 overexpression reduced reinstatement to a priming dose of cocaine in juvenile
      males. Together, these data show D1 expression may re-program motivational
      circuitry to facilitate extinction learning during juvenility that is normally
      unavailable to juveniles and that sex differences exist.

PMID- 25749359
TI  - Resting state BOLD functional connectivity at 3T: spin echo versus gradient echo
      EPI.
AB  - Previous evidence showed that, due to refocusing of static dephasing effects
      around large vessels, spin-echo (SE) BOLD signals offer an increased linearity
      and promptness with respect to gradient-echo (GE) acquisition, even at low field.
      These characteristics suggest that, despite the reduced sensitivity, SE fMRI
      might also provide a potential benefit when investigating spontaneous
      fluctuations of brain activity. However, there are no reports on the application
      of spin-echo fMRI for connectivity studies at low field. In this study we
      compared resting state functional connectivity as measured with GE and SE EPI
      sequences at 3T. Main results showed that, within subject, the GE sensitivity is
      overall larger with respect to that of SE, but to a less extent than previously
      reported for activation studies. Noteworthy, the reduced sensitivity of SE was
      counterbalanced by a reduced inter-subject variability, resulting in comparable
      group statistical connectivity maps for the two sequences. Furthermore, the SE
      method performed better in the ventral portion of the default mode network, a
      region affected by signal dropout in standard GE acquisition. Future studies
      should clarify if these features of the SE BOLD signal can be beneficial to
      distinguish subtle variations of functional connectivity across different
      populations and/or treatments when vascular confounds or regions affected by
      signal dropout can be a critical issue. 

PMID- 25749360
TI  - Safety and efficacy of micafungin for prophylaxis against invasive fungal
      infections in Japanese patients undergoing hematopoietic stem cell
      transplantation: Results of a post-marketing surveillance study.
AB  - Invasive fungal infections are a major cause of morbidity and mortality in
      patients with hematopoietic stem cell transplantation. A prospective multicenter
      post-marketing observational surveillance study was conducted from July 2007 to
      June 2010 to assess the safety and efficacy of micafungin, an echinocandin
      antifungal, for prophylaxis against invasive fungal infections in Japanese
      patients undergoing hematopoietic stem cell transplantation. Among 241 patients
      evaluated for safety, 143 adverse drug reactions were reported in 86 patients
      (35.7%), with hepatobiliary disorders the most frequently reported adverse drug
      reactions. The success rate for prophylaxis at the end of observation was 72.8%
      (131/180 patients), and the incidence of breakthrough infections was only 4.4%
      (8/180 patients). In conclusion, micafungin had sufficient safety and efficacy
      for prophylaxis against invasive fungal infections in Japanese patients with
      various backgrounds undergoing hematopoietic stem cell transplantation. 

PMID- 25749361
TI  - Agaricus section Arvenses: three new species in highland subtropical Southwest
      China.
AB  - Agaricus is a genus of saprobic basidiomycetes with more than 400 species
      recognized worldwide, with about 50 species known in China. Our objective was to
      investigate three new species of section Arvenses in highland subtropical
      Southwest China. Agaricus guizhouensis is a new species characterized by a white
      pileus with yellowish squamules, small ellipsoid spores and cheilocystidia with
      yellowish-brown pigments; another new species, Agaricus longistipes is recognized
      by its slender stipe, and its elongate-ellipsoid basidiospores; the third new
      one, Agaricus megalocarpus is remarkable by its large size and its pileus surface
      covered with fine brown squamules. It is firstly reported for Guizhou Province
      that Agaricus abruptibulbus, Agaricus flocculosipes, and Agaricus subrufescens
      are illustrated. Two probable new species require further studying. A
      phylogenetic analyses of rDNA-ITS sequence data belonging to section Arvenses
      showed that the section Arvenses is monophyletic and can be subdivided in five
      branches, the branch of A. subrufescens and four clades (A-D). The eight species
      from highland subtropical Southwest China were distributed in all five branches,
      indicating that this highland is at the climatic crossroads. The white pileus
      trait and the potential interest are discussed. These data suggest a potential
      species richness that remains to be discovered. 

PMID- 25749362
TI  - Candida and Fusarium species known as opportunistic human pathogens from customer
      accessible parts of residential washing machines.
AB  - Energy constraints have altered consumer practice regarding the use of household
      washing machines. Washing machines were developed that use lower washing
      temperatures, smaller amounts of water and biodegradable detergents. These
      conditions may favour the enrichment of opportunistic human pathogenic fungi. We
      focused on the isolation of fungi from two user-accessible parts of washing
      machines that often contain microbial biofilms: drawers for detergents and rubber
      door seals. Out of 70 residential washing machines sampled in Slovenia, 79% were
      positive for fungi. In total, 72 strains belonging to 12 genera and 26 species
      were isolated. Among these, members of the Fusarium oxysporum and Fusarium solani
      species complexes, Candida parapsilosis and Exophiala phaeomuriformis represented
      44% of fungi detected. These species are known as opportunistic human pathogens
      and can cause skin, nail or eye infections also in healthy humans. A machine
      learning analysis revealed that presence of detergents and softeners followed by
      washing temperature, represent most critical factors for fungal colonization.
      Three washing machines with persisting malodour that resulted in bad smelling
      laundry were analysed for the presence of fungi and bacteria. In these cases,
      fungi were isolated in low numbers (7.5 %), while bacteria Micrococcus luteus,
      Pseudomonas aeruginosa, and Sphingomonas species prevailed. 

PMID- 25749363
TI  - Proteomic profile of Aspergillus flavus in response to water activity.
AB  - Aspergillus flavus, a common contaminant of crops and stored grains, can produce
      aflatoxins that are harmful to humans and other animals. Water activity (aw) is
      one of the key factors influencing both fungal growth and mycotoxin production.
      In this study, we used the isobaric tagging for relative and absolute
      quantitation (iTRAQ) technique to investigate the effect of aw on the proteomic
      profile of A. flavus. A total of 3566 proteins were identified, of which 837 were
      differentially expressed in response to variations in aw. Among these 837
      proteins, 403 were over-expressed at 0.99 aw, whereas 434 proteins were over
      expressed at 0.93 aw. According to Gene Ontology (GO) analysis, the secretion of
      extracellular hydrolases increased as aw was raised, suggesting that
      extracellular hydrolases may play a critical role in induction of aflatoxin
      biosynthesis. On the basis of Clusters of Orthologous Groups (COG) and Kyoto
      Encyclopedia of Genes and Genomes (KEGG) categorizations, we identified an
      exportin protein, KapK, that may down-regulate aflatoxin biosynthesis by changing
      the location of NirA. Finally, we considered the role of two osmotic stress
      related proteins (Sln1 and Glo1) in the Hog1 pathway and investigated the
      expression patterns of proteins related to aflatoxin biosynthesis. The data
      uncovered in this study are critical for understanding the effect of water stress
      on toxin production and for the development of strategies to control toxin
      contamination of agricultural products. 

PMID- 25749364
TI  - The European race of Gremmeniella abietina hosts a single species of
      Gammapartitivirus showing a global distribution and possible recombinant events
      in its history.
AB  - The population genetics of the family Partitiviridae was studied within the
      European race of the conifer pathogen Gremmeniella abietina. One hundred sixty
      two isolates were collected from different countries, including Canada, the Czech
      Republic, Finland, Italy, Montenegro, Serbia, Spain, Switzerland, Turkey and the
      United States. A unique species of G. abietina RNA virus-MS1 (GaRV-MS1) appears
      to occur indistinctly in G. abietina biotypes A and B, without a particular
      geographical distribution pattern. Forty-six isolates were shown to host GaRV-MS1
      according to direct specific RT-PCR screening, and the virus was more common in
      biotype A than B. Phylogenetic analysis based on 46 partial coat protein (CP)
      cDNA sequences divided the GaRV-MS1 population into two closely related clades,
      while RNA-dependent RNA polymerase (RdRp) sequences revealed only one clade. The
      evolution of the virus appears to mainly occur through purifying selection but
      also through recombination. Recombination events were detected within alignments
      of the three complete CP and RdRp sequences of GaRV-MS1. This is the first time
      that recombination events have been directly identified in fungal partitiviruses
      and in G. abietina in particular. The results suggest that the population
      dynamics of GaRV-MS1 do not have a direct impact on the genetic structure of its
      host, G. abietina, though they might have had an innocuous ancestral
      relationship. 

PMID- 25749365
TI  - Combined morphological and molecular approach for identification of Stemphylium
      vesicarium inoculum in pear orchards.
AB  - Stemphylium vesicarium is the causal agent of brown spot of pear, an important
      disease reported in pear-growing areas of Europe. The pathogen is able to
      colonize pear leaf debris and dead tissues of herbaceous plants and produce
      abundant ascospores and conidia that are capable of infecting pear trees.
      Inoculum monitoring in pear orchards is mainly achieved through spore traps and
      species identification is based on conidial morphology, but the similarities on
      conidial traits among species of Stemphylium make correct identification
      difficult. In this work a total of thirty-seven Stemphylium isolates from pear
      orchards were characterized at the morphological, pathogenic, and molecular
      level. Correspondence among ITS and gpd sequences and morphological traits were
      evaluated. Species identification based exclusively on morphological data was not
      feasible. Combined morphological and molecular data were necessary for
      unambiguous identification of isolates in the S. vesicarium species group. Only
      isolates identified as S. vesicarium were pathogenic on pear. The study revealed
      that several species of Stemphylium coexist in pear orchards with S. vesicarium,
      the causal agent of BSP, and that combined morphological and molecular data are
      needed to differentiate them. Consequently, direct measurements of the airborne
      inoculum using volumetric spore traps may overestimate the actual pathogen
      population.

PMID- 25749366
TI  - Assessment of Ustilago maydis as a fungal model for root infection studies.
AB  - Ustilago maydis is a fungus infecting aerial parts of maize to form smutted
      galls. Due to its interest as a genetic tool in plant pathology, we evaluated its
      ability to penetrate into plant roots. The fungus can penetrate between epidermic
      root cells, forming inter and intracellular pseudohyphae. Root infection didn't
      provoke gall formation on the maize lines tested, and targeted PCR detection
      showed that U. maydis, unlike the other maize smut fungus Sporisorium reilianum,
      has a weak aptitude to grow from the roots up to the aerial part of maize. We
      also observed that U. maydis can infect Medicago truncatula hairy roots as an
      alternative host. This plant species is a model host to study root symbiosis, and
      this pathosystem can provide new insights on root-microbe interactions.
      Considering that U. maydis could be a soil fungus, we tested its responsiveness
      to GR24, a strigolactone analogue. Strigolactones are root exuded molecules which
      activate mitochondrial metabolism of arbuscular mycorrhizal (AM) fungi.
      Physiologic and molecular analysis revealed that GR24 also increases cell
      respiration of U. maydis. This result points out that strigolactones could have
      an incidence on several rhizospheric microbes. These data provide evidences that
      the biotrophic pathogen U. maydis has to be considered for studying root
      infection.

PMID- 25749367
TI  - Carbon and nitrogen limitation increase chitosan antifungal activity in
      Neurospora crassa and fungal human pathogens.
AB  - Chitosan permeabilizes plasma membrane and kills sensitive filamentous fungi and
      yeast. Membrane fluidity and cell energy determine chitosan sensitivity in fungi.
      A five-fold reduction of both glucose (main carbon (C) source) and nitrogen (N)
      increased 2-fold Neurospora crassa sensitivity to chitosan. We linked this
      increase with production of intracellular reactive oxygen species (ROS) and
      plasma membrane permeabilization. Releasing N. crassa from nutrient limitation
      reduced chitosan antifungal activity in spite of high ROS intracellular levels.
      With lactate instead of glucose, C and N limitation increased N. crassa
      sensitivity to chitosan further (4-fold) than what glucose did. Nutrient
      limitation also increased sensitivity of filamentous fungi and yeast human
      pathogens to chitosan. For Fusarium proliferatum, lowering 100-fold C and N
      content in the growth medium, increased 16-fold chitosan sensitivity. Similar
      results were found for Candida spp. (including fluconazole resistant strains) and
      Cryptococcus spp. Severe C and N limitation increased chitosan antifungal
      activity for all pathogens tested. Chitosan at 100 MUg ml(-1) was lethal for most
      fungal human pathogens tested but non-toxic to HEK293 and COS7 mammalian cell
      lines. Besides, chitosan increased 90% survival of Galleria mellonella larvae
      infected with C. albicans. These results are of paramount for developing chitosan
      as antifungal. 

PMID- 25749368
TI  - Occurrence and genetic diversity of the Plasmopara halstedii virus in sunflower
      downy mildew populations of the world.
AB  - Plasmopara halstedii virus (PhV) is a ss(+)RNA virus that exclusively occurs in
      the sunflower downy mildew pathogen Plasmopara halstedii, a biotrophic oomycete
      of severe economic impact. The virus origin and its genomic variability are
      unknown. A PCR-based screening of 128 samples of P. halstedii from five
      continents and up to 40 y old was conducted. PhV RNA was found in over 90 % of
      the isolates with no correlation to geographic origin or pathotype of its host.
      Sequence analyses of the two open reading frames (ORFs) revealed only 18 single
      nucleotide polymorphisms (SNPs) in 3873 nucleotides. The SNPs had no recognizable
      effect on the two encoded virus proteins. In 398 nucleotides of the untranslated
      regions (UTRs) of the RNA 2 strand eight additional SNPs and one short deletion
      was found. Modelling experiments revealed no effects of these variations on the
      secondary structure of the RNA. The results showed the presence of PhV in P.
      halstedii isolates of global origin and the existence of the virus since more
      than 40 y. The virus genome revealed a surprisingly low variation in both coding
      and noncoding parts. No sequence differences were correlated with host pathotype
      or geographic populations of the oomycete. 

PMID- 25749369
TI  - Structural stability and functional remodeling of high-density lipoproteins.
AB  - Lipoproteins are protein-lipid nanoparticles that transport lipids in circulation
      and are central in atherosclerosis and other disorders of lipid metabolism.
      Apolipoproteins form flexible structural scaffolds and important functional
      ligands on the particle surface and direct lipoprotein metabolism. Lipoproteins
      undergo multiple rounds of metabolic remodeling that is crucial to lipid
      transport. Important aspects of this remodeling, including apolipoprotein
      dissociation and particle fusion, are mimicked in thermal or chemical
      denaturation and are modulated by free energy barriers. Here we review the
      biophysical studies that revealed the kinetic mechanism of lipoprotein
      stabilization and unraveled its structural basis. The main focus is on high
      density lipoprotein (HDL). An inverse correlation between stability and functions
      of various HDLs in cholesterol transport suggests the functional role of
      structural disorder. A mechanism for the conformational adaptation of the major
      HDL proteins, apoA-I and apoA-II, to the increasing lipid load is proposed.
      Together, these studies help understand why HDL forms discrete subclasses
      separated by kinetic barriers, which have distinct composition, conformation and
      functional properties. Understanding these properties may help improve HDL
      quality and develop novel therapies for cardiovascular disease. 

PMID- 25749370
TI  - Quantitative assessment of telomerase components in cancer cell lines.
AB  - Besides its canonical function of catalyzing the formation of telomeric repeats,
      many groups have recently reported non-canonical functions of hTERT in
      particular, and telomerase in general. Regulating transcription is the central
      basis of non-canonical functions of telomerase. However, unlike reverse
      transcriptase activity of telomerase that requires only a few molecules of
      enzymatically active hTERT, non-canonical functions of hTERT or other telomerase
      components theoretically require several hundred copies. Here, we provide the
      first direct quantification of all the telomerase components in human cancer cell
      lines. We demonstrate that telomerase components do not exist in a 1:1
      stoichiometric ratio, and there are several hundred copies of hTERT in cells.
      This provides the molecular basis of hTERT to function in other signaling
      cascades, including transcription. 

PMID- 25749372
TI  - Modeling the effect of reflective calf hutch covers on reducing heat loss.
AB  - This study determined if a reflective film could theoretically be useful in
      moderating the rate of heat loss from calves housed in polyethylene hutches
      during cold weather. An engineering approach was used in which rate of heat loss
      was modeled using 38-l steel drums filled with body temperature water and covered
      by fresh calf hide. The reflective film (cover) consisted of aluminized 0.0635 mm
      low-density olive color polyethylene. The non-reflective olive side was sprayed
      with flat black paint. Covers were 1.8 * 3 m with the aluminized side facing the
      hutch. Two of four hutches were either uncovered or had covers across the top and
      sides. During the night, (mean temperature +/- SE -13.6 +/- 0.29  degrees C), the
      rate of temperature loss was -0.21  degrees C per 5-min interval over 28
      temperature readings in the covered and -0.25  degrees C in the uncovered (R (2)
      = 0.99). During the daytime (mean +/- SE 14.3 +/- 0.52  degrees C), rate of heat
      loss was -0.15  degrees C per 5-min interval over 33 temperature readings in the
      covered and -0.11  degrees C in the uncovered (R (2) = 0.99). Reflective film
      reduced the rate of heat loss during cold nights, but when the sun was shining on
      the hutches during midday, the uncovered hutches warmed up more and, hence,
      reduced the rate of heat loss when compared to the covered. Further research is
      needed on the orientation of hutches in relationship to the sun and with live
      calves because calves would be able to move into the sun during cold sunny days.

PMID- 25749373
TI  - Neurodegenerative diseases in the era of targeted therapeutics: how to handle a
      tangled issue.
AB  - Neurodegenerative diseases are age-related and relentlessly progressive with
      increasing prevalence and no cure or lasting symptomatic therapy. The well
      recognized prodromal phase in many forms of neurodegeneration suggests a
      prolonged period of neuronal compensated dysfunction prior to cell loss that may
      be amenable to therapeutic intervention. Although most efforts to date have been
      focused on misfolded toxic proteins, it is now clear that widespread changes in
      protein homeostasis occur early in these diseases and understanding this
      fundamental biology is key to the design of targeted therapies. What has emerged
      from molecular genetics and animal studies is a previously less appreciated
      association of neurodegenerative diseases with defects in the molecular
      regulation of protein trafficking between cellular organelles, especially the
      intricate network of endosomes, lysosomes, autophagosomes and mitochondria. Here
      we summarized the broader concepts that stemmed from this Special Issue on
      "Protein Clearance in Neurodegenerative diseases: from mechanisms to therapies".
      This article is part of a Special Issue entitled 'Neuronal Protein'. 

PMID- 25749374
TI  - WNK1 is involved in Nogo66 inhibition of OPC differentiation.
AB  - LINGO-1 is a transmembrane receptor expressed primarily in the central nervous
      system (CNS) and plays an important role in myelination. Recent studies have
      indicated that it is also involved in oligodendrocyte precursor cell (OPC)
      survival and differentiation; however, the downstream signaling pathway
      underlying OPC development is unknown. In our previous study, we found that LINGO
      1 is associated with WNK1 in mediating Nogo-induced neurite extension inhibition
      by RhoA activation. In an effort to identify the role of LINGO-1-WNK1 in OPCs, we
      first confirmed that WNK1 is also expressed in OPCs and co-localized with LINGO
      1, which suppresses WNK1 expression by RNA interference-attenuated Nogo66-induced
      inhibition of OPC differentiation. Furthermore, we mapped the WNK1 kinase domain
      using several fragmented peptides to identify the key region of interaction with
      LINGO-1. We found that a sequence corresponding to the D6 peptide is necessary
      for the interaction. Finally, we found that using the TAT-D6 peptide to introduce
      D6 peptide into primary cultured OPC inhibits the association between LINGO-1 and
      WNK1 and significantly attenuates Nogo66-induced inhibition of OPC
      differentiation. Taken together, our results show that WNK1, via a specific
      region on WNK1 kinase domain, interacts with LINGO-1, thus mediating Nogo66
      inhibited OPC differentiation. 

PMID- 25749371
TI  - Advances in reprogramming-based study of neurologic disorders.
AB  - The technology to convert adult human non-neural cells into neural lineages,
      through induced pluripotent stem cells (iPSCs), somatic cell nuclear transfer,
      and direct lineage reprogramming or transdifferentiation has progressed
      tremendously in recent years. Reprogramming-based approaches aimed at
      manipulating cellular identity have enormous potential for disease modeling, high
      throughput drug screening, cell therapy, and personalized medicine. Human iPSC
      (hiPSC)-based cellular disease models have provided proof of principle evidence
      of the validity of this system. However, several challenges remain before patient
      specific neurons produced by reprogramming can provide reliable insights into
      disease mechanisms or be efficiently applied to drug discovery and
      transplantation therapy. This review will first discuss limitations of currently
      available reprogramming-based methods in faithfully and reproducibly
      recapitulating disease pathology. Specifically, we will address issues such as
      culture heterogeneity, interline and inter-individual variability, and
      limitations of two-dimensional differentiation paradigms. Second, we will assess
      recent progress and the future prospects of reprogramming-based neurologic
      disease modeling. This includes three-dimensional disease modeling, advances in
      reprogramming technology, prescreening of hiPSCs and creating isogenic disease
      models using gene editing. 

PMID- 25749375
TI  - Transition-metal-catalyzed direct addition of unactivated C-H bonds to polar
      unsaturated bonds.

PMID- 25749376
TI  - Can ionization mass spectrometry coupled with ultrasonic scalpel a fine detection
      method for intraoperative pathological analysis?
AB  - Ionization mass spectrometry (IMS) has been reported to detect surgical smoke
      component and analyze the distribution of phospholipids found in the smoke. Based
      on the previous studies, electrosurgical and laser knife coupled IMS has been
      reported to assess pathogenic diagnosis such as tumor malignancy and to guide
      tumor resection such as real-time surgical margin control. In addition, US
      operation is a more closed space for smoke detection than the others. Thus, in
      this study we speculate that ultrasonic scalpel (US) generated smoke could also
      be detected, which might has a better detection effect and the assessment would
      has a fine application prospect. 

PMID- 25749377
TI  - Periodontitis as a risk factor for systemic disease: Are microparticles the
      missing link?
AB  - Periodontitis is an oral inflammatory disease affecting the teeth supportive
      tissue. Its bacterial infectious etiology is well established. Periodontitis has
      been associated with increased prevalence of systemic diseases such as
      cardiovascular diseases, diabetes, rheumatoid arthritis, preeclampsia, preterm
      birth and inflammatory bowel disease. The rational of considering periodontitis
      as risk factor for systemic disease is the passage of inflammatory cytokines
      and/or bacteria in the bloodstream, thus affecting distant organs. Membrane
      microparticles are released by multiple cells in inflammatory environment. Recent
      data suggested the role of these microparticles in the pathogenic process of many
      systemic diseases, that can be also associated to periodontitis. We hypothesized
      that periodontitis could be a chronic reservoir of microparticles, hence
      elucidating partially the interaction with systemic diseases initiation or
      progression. 

PMID- 25749378
TI  - Identification of a novel synthetic lethality of combined inhibition of hedgehog
      and PI3K signaling in rhabdomyosarcoma.
AB  - We previously reported that aberrant HH pathway activation confers a poor
      prognosis in rhabdomyosarcoma (RMS). Searching for new treatment strategies we
      therefore targeted HH signaling. Here, we identify a novel synthetic lethality of
      concomitant inhibition of HH and PI3K/AKT/mTOR pathways in RMS by GLI1/2
      inhibitor GANT61 and PI3K/mTOR inhibitor PI103. Synergistic drug interaction is
      confirmed by calculation of combination index (CI < 0.2). Similarly, genetic
      silencing of GLI1/2 significantly increases PI103-induced apoptosis. GANT61 and
      PI103 also synergize to induce apoptosis in cultured primary RMS cells
      emphasizing the clinical relevance of this combination. Importantly, GANT61/PI103
      cotreatment suppresses clonogenic survival, three-dimensional sphere formation
      and tumor growth in an in vivo model of RMS. Mechanistic studies reveal that
      GANT61 and PI103 cooperate to trigger caspase-dependent apoptosis via the
      mitochondrial pathway, as demonstrated by several lines of evidence. First,
      GANT61/PI103 cotreatment increases mRNA and protein expression of NOXA and BMF,
      which is required for apoptosis, since knockdown of NOXA or BMF significantly
      reduces GANT61/PI103-induced apoptosis. Second, GANT61/PI103 cotreatment triggers
      BAK/BAX activation, which contributes to GANT61/PI103-mediated apoptosis, since
      knockdown of BAK provides protection. Third, ectopic expression of BCL-2 or non
      degradable phospho-mutant MCL-1 significantly rescue GANT61/PI103-triggered
      apoptosis. Fourth, GANT61/PI103 cotreatment initiate activation of the caspase
      cascade via apoptosome-mediated cleavage of the initiator caspase-9, as indicated
      by changes in the cleavage pattern of caspases (e.g. accumulation of the caspase
      9 p35 cleavage fragment) upon addition of the caspase inhibitor zVAD.fmk. Thus,
      combined GLI1/2 and PI3K/mTOR inhibition represents a promising novel approach
      for synergistic apoptosis induction and tumor growth reduction with implications
      for new treatment strategies in RMS. 

PMID- 25749379
TI  - Enzastaurin inhibits ABCB1-mediated drug efflux independently of effects on
      protein kinase C signalling and the cellular p53 status.
AB  - The PKCbeta inhibitor enzastaurin was tested in parental neuroblastoma and
      rhabdomyosarcoma cell lines, their vincristine-resistant sub-lines, primary
      neuroblastoma cells, ABCB1-transduced, ABCG2-transduced, and p53-depleted cells.
      Enzastaurin IC50s ranged from 3.3 to 9.5 MUM in cell lines and primary cells
      independently of the ABCB1, ABCG2, or p53 status. Enzastaurin 0.3125 MUM
      interfered with ABCB1-mediated drug transport. PKCalpha and PKCbeta may
      phosphorylate and activate ABCB1 under the control of p53. However, enzastaurin
      exerted similar effects on ABCB1 in the presence or absence of functional p53.
      Also, enzastaurin inhibited PKC signalling only in concentrations >= 1.25 MUM.
      The investigated cell lines did not express PKCbeta. PKCalpha depletion reduced
      PKC signalling but did not affect ABCB1 activity. Intracellular levels of the
      fluorescent ABCB1 substrate rhodamine 123 rapidly decreased after wash-out of
      extracellular enzastaurin, and enzastaurin induced ABCB1 ATPase activity
      resembling the ABCB1 substrate verapamil. Computational docking experiments
      detected a direct interaction of enzastaurin and ABCB1. These data suggest that
      enzastaurin directly interferes with ABCB1 function. Enzastaurin further
      inhibited ABCG2-mediated drug transport but by a different mechanism since it
      reduced ABCG2 ATPase activity. These findings are important for the further
      development of therapies combining enzastaurin with ABC transporter substrates.

PMID- 25749380
TI  - Detection of high mobility group A2 specific mRNA in the plasma of patients
      affected by epithelial ovarian cancer.
AB  - Ovarian cancer is the most lethal gynecological malignancy and the high mortality
      rate is associated with advanced-stage disease at the time of the diagnosis. In
      order to find new tools to make diagnosis of Epithelial Ovarian Cancer (EOC) at
      early stages we have analyzed the presence of specific HMGA2 mRNA in the plasma
      of patients affected by this neoplasm. HMGA2 overexpression represents a feature
      of several malignances including ovarian carcinomas. Notably, we detected HMGA2
      specific mRNA in the plasma of 40 out 47 patients with EOC, but not in the plasma
      of healthy donors. All cases found positive for HMGA2 mRNA in the plasma showed
      HMGA2 protein expression in EOC tissues. Therefore, on the basis of these
      results, the analysis of circulating HMGA2 specific mRNA might be considered a
      very promising tool for the early diagnosis of EOC. 

PMID- 25749381
TI  - CSIG promotes hepatocellular carcinoma proliferation by activating c-MYC
      expression.
AB  - Cellular senescence-inhibited gene (CSIG) protein significantly prolongs the
      progression of replicative senescence, but its role in tumorigenesis is unclear.
      To reveal the role of CSIG in HCC, we determined its expression in HCC tissues
      and surrounding tissues and its functions in tumor cell proliferation in vitro
      and in vivo. CSIG protein was overexpressed in 86.4% of the human HCC cancerous
      tissues as compared with matched surrounding tissues, and its protein expression
      was greater in HCC cells than the non-transformed hepatic cell line L02.
      Furthermore, upregulation of CSIG significantly increased the colony formation of
      SMMC7721 and HepG2 cells, and silencing CSIG could induce cell cycle arrest and
      cell apoptosis. The tumorigenic ability of CSIG was confirmed in vivo in a mouse
      xenograft model. Our results showed that CSIG promoted the proliferation of HepG2
      and SMMC7721 cells in vivo. Finally, CSIG protein directly interacted with c-MYC
      protein and increased c-MYC protein levels; the ubiquitination and degradation of
      c-MYC protein was increased with knockdown of CSIG. CSIG could also increase the
      expression of c-MYC protein in SMMC7721 cells in vivo, and it was noted that the
      level of c-MYC protein was also elevated in most human cancerous tissues with
      high level of CSIG. 

PMID- 25749382
TI  - The histone code reader SPIN1 controls RET signaling in liposarcoma.
AB  - The histone code reader Spindlin1 (SPIN1) has been implicated in tumorigenesis
      and tumor growth, but the underlying molecular mechanisms remain poorly
      understood. Here, we show that reducing SPIN1 levels strongly impairs
      proliferation and increases apoptosis of liposarcoma cells in vitro and in
      xenograft mouse models. Combining signaling pathway, genome-wide chromatin
      binding, and transcriptome analyses, we found that SPIN1 directly enhances
      expression of GDNF, an activator of the RET signaling pathway, in cooperation
      with the transcription factor MAZ. Accordingly, knockdown of SPIN1 or MAZ results
      in reduced levels of GDNF and activated RET explaining diminished liposarcoma
      cell proliferation and survival. In line with these observations, levels of
      SPIN1, GDNF, activated RET, and MAZ are increased in human liposarcoma compared
      to normal adipose tissue or lipoma. Importantly, a mutation of SPIN1 within the
      reader domain interfering with chromatin binding reduces liposarcoma cell
      proliferation and survival. Together, our data describe a molecular mechanism for
      SPIN1 function in liposarcoma and suggest that targeting SPIN1 chromatin
      association with small molecule inhibitors may represent a novel therapeutic
      strategy. 

PMID- 25749383
TI  - Osteopontin promotes a cancer stem cell-like phenotype in hepatocellular
      carcinoma cells via an integrin-NF-kappaB-HIF-1alpha pathway.
AB  - There is increasing evidence to suggest that hepatocellular carcinomas (HCCs) are
      sustained by a distinct subpopulation of self-renewing cells known as cancer stem
      cells. However, the precise signals required for maintenance of stemness-like
      properties of these cells are yet to be elucidated. Here, we demonstrated that
      the level of oncoprotein osteopontin (OPN) in tumor cells of the edge of bulk
      tumors was significantly correlated with the clinical prognosis of patients with
      HCC. OPN was highly expressed in side population fractions of HCC cell lines, as
      well as in dormant cells, spheroids and chemo-resistant cancer cells, all of
      which are considered as having stemness-like cellular features. Depletion of OPN
      in HCC cell lines resulted in a reduction in the proportion of side population
      fractions, formation of hepato-spheroids, expression of stem-cell-associated
      genes and decreased tumorigenecity in immunodeficient mice. Mechanistically, OPN
      was demonstrated to bind to integrin alphavbeta3 and activate the transcription
      factor NF-kappaB, which resulted in upregulation of HIF-1alpha transcription and
      its downstream gene, BMI1, to mediate maintenance of the stemness-like phenotype.
      Suppression of the alphavbeta3-NF-kappaB-HIF-1alpha pathway decreased OPN
      mediated self-renewal capabilities. Levels of OPN protein expression were
      significantly correlated with HIF-1alpha protein levels in HCC tumor tissue
      samples. OPN might promote a cancer stem cell-like phenotype via the alphavbeta3
      NF-kappaB-HIF-1alpha pathway. Our findings offer strong support for OPN
      requirement in maintaining stem-like properties in HCC cells. 

PMID- 25749384
TI  - Fibrillin-1, induced by Aurora-A but inhibited by BRCA2, promotes ovarian cancer
      metastasis.
AB  - While Aurora-A (Aur A) provokes, BRCA2 restrains primary tumorigenesis, the roles
      of Aur A and BRCA2 in cancer metastasis remains unclear. Here, we show that the
      metastatic promoting markers SLUG, FBN1, and MMP2, 9, 13 are either stimulated or
      suppressed by Aur A or BRCA2, but the metastatic suppressors E-cadherin, beta
      catenin, and p53 are either inhibited or promoted by Aur A or BRCA2, leading to
      enhanced or reduced cell migration and invasion. Further study suggests that FBN1
      inhibits E-cadherin and beta-catenin, but stimulates MMP2, 9, 13. Depletion of
      SLUG abrogates FBN1 and MMP9, but increases E-cadherin, while p53 decreases both
      SLUG and FBN1. Animal assays demonstrate that FBN1 promotes both ovarian
      tumorigenesis and metastasis. Clinically, overexpression of BRCA2 or Aur A in
      ovarian cancer tissues predicts good or poor overall and disease free survivals.
      High expression of SLUG or FBN1 indicates poor overall survivals, whereas high
      expression of FBN1 but not of SLUG predicts poor disease free survival. No
      significant associations between p53 expression and patient survivals were found.
      Overall, FBN1, acts at the downstream of Aur A and BRCA2, promotes ovarian cancer
      metastasis through the p53 and SLUG-associated signaling, which may be useful for
      ovarian cancer diagnosis and treatment. 

PMID- 25749385
TI  - G9a is essential for EMT-mediated metastasis and maintenance of cancer stem cell
      like characters in head and neck squamous cell carcinoma.
AB  - Head and neck squamous cell carcinoma (HNSCC) is a particularly aggressive cancer
      with poor prognosis, largely due to lymph node metastasis and local recurrence.
      Emerging evidence suggests that epithelial-to-mesenchymal transition (EMT) is
      important for cancer metastasis, and correlated with increased cancer stem cells
      (CSCs) characteristics. However, the mechanisms underlying metastasis to lymph
      nodes in HNSCC is poorly defined. In this study, we show that E-cadherin
      repression correlates with cancer metastasis and poor prognosis in HNSCC. We
      found that G9a, a histone methyltransferase, interacts with Snail and mediates
      Snail-induced transcriptional repression of E-cadherin and EMT, through
      methylation of histone H3 lysine-9 (H3K9). Moreover, G9a is required for both
      lymph node-related metastasis and TGF-beta-induced EMT in HNSCC cells since
      knockdown of G9a reversed EMT, inhibited cell migration and tumorsphere
      formation, and suppressed the expression of CSC markers. Our study demonstrates
      that the G9a protein is essential for the induction of EMT and CSC-like
      properties in HNSCC. Thus, targeting the G9a-Snail axis may represent a novel
      strategy for treatment of metastatic HNSCC. 

PMID- 25749386
TI  - Radiation-induced PGE2 sustains human glioma cells growth and survival through
      EGF signaling.
AB  - Glioblastoma Multiforme (GBM) is the most common brain cancer in adults.
      Radiotherapy (RT) is the most effective post-operative treatment for the patients
      even though GBM is one of the most radio-resistant tumors. Dead or dying cells
      within the tumor are thought to promote resistance to treatment through
      mechanisms that are very poorly understood. We have evaluated the role of
      Prostaglandin E2 (PGE2), a versatile bioactive lipid, in GBM radio-resistance. We
      used an in vitro approach using 3D primary cultures derived from representative
      GBM patients. We show that irradiated glioma cells produced and released PGE2 in
      important quantities independently of the induction of cell death. We demonstrate
      that the addition of PGE2 enhances cell survival and proliferation though its
      ability to trans-activate the Epithelial Growth Factor receptor (EGFR) and to
      activate beta-catenin. Indeed, PGE2 can substitute for EGF to promote primary
      cultures survival and growth in vitro and the effect is likely to occur though
      the Prostaglandin E2 receptor EP2. 

PMID- 25749387
TI  - The miR-491-3p/mTORC2/FOXO1 regulatory loop modulates chemo-sensitivity in human
      tongue cancer.
AB  - We found that levels of miR-491-3p were decreased in multidrug-resistant tongue
      cancer (TC) cells. Induction of miR-491-3p expression sensitized TC cells to
      chemotherapy. In agreement, functional inhibition of miR-491-3p enhanced
      resistance of TC cells to chemotherapy. We found that miR-491-3p directly
      targeted mTORC2 component Rictor and inhibited mTORC2 activity, which was
      increased in resistant TC cells with high p-Akt(Ser473), p-SGK1(Ser422) and p
      FOXO1(Thr24) levels. Inhibition of mTORC2 activity via either Rictor knockdown or
      mTOR inhibitor in turn sensitized TC cells to chemotherapy. In agreement,
      overexpression of Rictor increased the mTORC2 activity and induced resistance of
      TC cells to chemotherapy. As a feedback loop, mTORC2 downregulated miR-491-3p
      expression by inactivating FOXO1, which otherwise would transcriptionally induce
      miR-491-3p expression. Levels of miR-491-3 and Rictor or mTORC2 activity
      negatively correlated in TC tissues. Finally, low levels of miR-491-3p and highly
      expressed Rictor were associated with poor prognosis in tongue cancer patients.
      These data provide a rationale for targeted intervention on miR-491-3p/mTORC2
      axis to enhance the efficacy of chemotherapy against tongue cancer. 

PMID- 25749390
TI  - EPA guidance on the early intervention in clinical high risk states of psychoses.
AB  - This guidance paper from the European Psychiatric Association (EPA) aims to
      provide evidence-based recommendations on early intervention in clinical high
      risk (CHR) states of psychosis, assessed according to the EPA guidance on early
      detection. The recommendations were derived from a meta-analysis of current
      empirical evidence on the efficacy of psychological and pharmacological
      interventions in CHR samples. Eligible studies had to investigate conversion rate
      and/or functioning as a treatment outcome in CHR patients defined by the ultra
      high risk and/or basic symptom criteria. Besides analyses on treatment effects on
      conversion rate and functional outcome, age and type of intervention were
      examined as potential moderators. Based on data from 15 studies (n=1394), early
      intervention generally produced significantly reduced conversion rates at 6- to
      48-month follow-up compared to control conditions. However, early intervention
      failed to achieve significantly greater functional improvements because both
      early intervention and control conditions produced similar positive effects. With
      regard to the type of intervention, both psychological and pharmacological
      interventions produced significant effects on conversion rates, but not on
      functional outcome relative to the control conditions. Early intervention in
      youth samples was generally less effective than in predominantly adult samples.
      Seven evidence-based recommendations for early intervention in CHR samples could
      have been formulated, although more studies are needed to investigate the
      specificity of treatment effects and potential age effects in order to tailor
      interventions to the individual treatment needs and risk status. 

PMID- 25749388
TI  - NDRG4, a novel candidate tumor suppressor, is a predictor of overall survival of
      colorectal cancer patients.
AB  - The role of NDRG4 in human malignancies is largely unknown. We investigated the
      role of NDRG4 protein in colorectal cancer and its prognostic value in a hospital
      based retrospective training cohort of 272 patients and a prospective validation
      cohort of 708 patients were. Cell line was transfected with an NDRG4 expression
      construct to confirm the suppression of PI3K-AKT activity by NDRG4. Appropriate
      statistical methods were utilized for analysis. Results showed that NDRG4 protein
      expression was significantly decreased from normal mucosa, chronic colitis,
      ulcerative colitis, atypical hyperplasia to colorectal cancer. Significant
      negative correlations were found between NDRG4 staining and p-AKT. Patients with
      positive NDRG4 staining had favorable survival in both study cohorts. In
      multivariate analysis, NDRG4 staining proved to be an independent predictor of
      overall survival. Moreover, the prognostic role of NDRG4 was stratified by p-AKT.
      Overexpression of NDRG4 in colorectal cancer cell can significantly suppress PI3K
      AKT activity, even after EGF stimulation. These results indicated NDRG4 protein
      expression was decreased in colorectal cancer. It may play its tumor suppressive
      role in carcinogenesis and progression through attenuation of PI3K-AKT activity.
      Therefore, high risk colorectal cancer patients could be better identified based
      on the combination of NDRG4 and PI3K-AKT activity.

PMID- 25749389
TI  - Circular RNA ITCH has inhibitory effect on ESCC by suppressing the Wnt/beta
      catenin pathway.
AB  - Circular RNAs with exonic sequences represent a special form of non-coding RNAs,
      discovered by analyzing a handful of transcribed genes. It has been observed that
      circular RNAs function as microRNA sponges. In the present study, we investigated
      whether the expression of circular RNAs is altered during the development of
      esophageal squamous cell carcinoma (ESCC). Using a TaqMan-based reverse
      transcriptase polymerase chain reaction assay, the relationship between cir-ITCH
      and ESCC was analyzed in a total of 684 ESCC and paired adjacent non-tumor tissue
      samples from eastern and southern China. We found that cir-ITCH expression was
      usually low in ESCC compared to the peritumoral tissue. The functional relevance
      of cir-ITCH was further examined by biochemical assays. As sponge of miR-7, miR
      17, and miR-214, cir-ITCH might increase the level of ITCH. ITCH hyper expression
      promotes ubiquitination and degradation of phosphorylated Dvl2, thereby
      inhibiting the Wnt/beta-catenin pathway. These results indicate that cir-ITCH may
      have an inhibitory effect on ESCC by regulating the Wnt pathway. 

PMID- 25749391
TI  - Time to local recurrence as a prognostic factor in patients with rectal cancer.
AB  - AIMS: Survival after the local recurrence of rectal cancer is influenced by
      several factors. The aim of this study was to ascertain whether the time interval
      from primary surgery for rectal cancer to local recurrence diagnosis has any
      impact on survival. METHODS: Population-based data was collected from the Swedish
      Colorectal Cancer Registry. 7410 patients were operated with radical abdominal
      surgery for rectal cancer during the period 1995-2002. Of these, 386 (5%)
      developed a local recurrence as a first event. The patients were divided into two
      groups: early local recurrence (ELR), diagnosed <12 months after primary surgery,
      and late local recurrence (LLR), diagnosed >=12 months after primary surgery.
      Kaplan-Meier curves and hazard ratios were calculated for survival analyses.
      Survival was calculated from the date of the local recurrence diagnosis to death
      or end of follow-up. RESULTS: Ninety-five patients had ELR and 291 patients LLR.
      Median time to local recurrence was 1.7 (0.1-7.9) years. Patients with a stage
      III primary tumour and non-irradiated patients were more common in the ELR
      compared with the LLR group. Factors that influenced survival were age at
      diagnosis of local recurrence (p < 0.001), stage of primary tumour (p = 0.027),
      and surgical resection of local recurrence (p < 0.001). Time to diagnosis of
      local recurrence had no influence on survival. CONCLUSIONS: No difference in
      survival from date of diagnosis of local recurrence was seen between patients
      with ELR and patients with LLR. All patients with local recurrence should
      therefore be assessed for potential curative surgery, disregarding time to local
      recurrence.

PMID- 25749392
TI  - Medication adherence in type 2 diabetes patients in Nigeria.
AB  - BACKGROUND: Medication adherence is a major universal factor influencing patient
      health outcomes, particularly in chronic diseases such as diabetes. Poor
      adherence to antidiabetes medication can cause therapeutic failure, leading to
      manifestation of diabetes-related complications, such as retinopathy, neuropathy,
      nephropathy, etc., reduced quality of life, and increased healthcare costs. To
      forestall these, likely predictors of medication nonadherence should be assessed
      and addressed appropriately. The purpose of this work was therefore to assess
      medication adherence among type 2 diabetes patients and to identify patient
      characteristics and probable factors associated with nonadherence. SUBJECTS AND
      METHODS: A descriptive, cross-sectional research design was used. The study was
      conducted on 360 ambulatory type 2 diabetes patients attending an endocrinology
      clinic between June 2012 and February 2013. The eight-item Modified Morisky
      Adherence Scale was used to assess medication adherence; sociodemographic
      information and respondents' opinion on the possible barrier(s) to medication
      adherence were also obtained. Data were analyzed using SPSS version 14.0 software
      (SPSS, Inc., Chicago, IL). RESULTS: Of the 303 patients included in the final
      analysis, 19.8% of respondents were judged to be highly adherent. Medium and low
      adherers were 30.0% and 50.2%, respectively. The median adherence score was 5.75
      (interquartile range, 4.5-7.0). Adherence to medication correlated with low
      literacy level (P=0.008), forgetfulness (P=0.009), high cost of medication
      (P=0.014), limited access to care (P=0.001), complexity of regimen (P=0.001),
      poor patient-provider communication (P=0.000), lack of trust in the provider
      (P=0.046), and depression (P=0.031). No statistically significant relationship
      was found between patients' characteristics and medication adherence.
      CONCLUSIONS: Medication adherence was generally poor among the cohorts studied.

PMID- 25749393
TI  - 2014 update on interventional cardiology.
AB  - This article reviews the most relevant publications and studies in the field of
      interventional cardiology in 2014. In the area of coronary interventional
      procedures, integrated treatment of acute coronary syndrome continues to be the
      subject of numerous studies that evaluate different devices and pharmacological
      and mechanical strategies that can be used without increasing the risk of
      hemorrhage or the need for reintervention. Certain anatomical substrates continue
      to generate a considerable number of publications, both on the outcomes with
      different stents and on the use of specific techniques. Bioabsorbable drug
      eluting stents are used in increasingly complex lesions with promising results.
      The development of interventional procedures for structural heart disease
      continues to advance, with new evidence on percutaneously placed aortic valve
      prostheses, the outcome of percutaneous mitral valve repair, and the safety and
      efficacy of left atrial appendage occlusion. Finally, renal denervation has
      generated one of the major debates of the year. 

PMID- 25749394
TI  - DNA vaccination with genes encoding Toxoplasma gondii antigens ROP5 and GRA15
      induces protective immunity against toxoplasmosis in Kunming mice.
AB  - OBJECTIVES: To evaluate the protective efficacy of a DNA vaccine encoding
      Toxoplasma gondii rhoptry protein 5 (ROP5) and GRA15 antigens. METHODS: We
      constructed eukaryotic plasmids expressing pVAX-ROP5 and pVAX-GRA15, and measured
      the immune responses to these DNA vaccines. RESULTS: Kunming mice immunized with
      pVAX-ROP5 or pVAX-GRA15 showed significantly increased serum IgG2a titers; Th1
      responses association with the production of IFN-gamma, IL-2, IL12 p40 and IL-12
      p70; cell-mediated cytotoxic activity with increased frequencies of IFN-gamma
      secreting CD8(+) T cells (CD8(+) IFN-gamma+ T cells), as well as prolonged
      survival time (19.4 +/- 4.9 days for ROP5; 17.8 +/- 3.8 days for GRA15) and brain
      cyst reduction (57.4% for ROP5; 65.9% for GRA15) compared to control mice. Co
      administration with pVAX-ROP5 and pVAX-GRA15 boosted the cellular and humoral
      immune responses, and significantly increased cyst reduction (79%) and prolonged
      the survival of immunized mice (22.7 +/- 7.2 days). CONCLUSION: Co-immunization
      of pVAX-ROP5 and pVAX-GRA15 increase the protective efficacy.

PMID- 25749395
TI  - Translational research: innovative intervention strategies for promoting child
      and adolescent health and improving the quality of pediatric nursing practice.

PMID- 25749396
TI  - "And I think that we can fix it": mental models used in high-risk surgical
      decision making.
AB  - OBJECTIVE: To examine how surgeons use the "fix-it" model to communicate with
      patients before high-risk operations. BACKGROUND: The "fix-it" model
      characterizes disease as an isolated abnormality that can be restored to normal
      form and function through medical intervention. This mental model is familiar to
      patients and physicians, but it is ineffective for chronic conditions and
      treatments that cannot achieve normalcy. Overuse may lead to permissive decision
      making favoring intervention. Efforts to improve surgical decision making will
      need to consider how mental models function in clinical practice, including "fix
      it." METHODS: We observed surgeons who routinely perform high-risk surgery during
      preoperative discussions with patients. We used qualitative content analysis to
      explore the use of "fix-it" in 48 audio-recorded conversations. RESULTS: Surgeons
      used the "fix-it" model for 2 separate purposes during preoperative
      conversations: (1) as an explanatory tool to facilitate patient understanding of
      disease and surgery, and (2) as a deliberation framework to assist in decision
      making. Although surgeons commonly used "fix-it" as an explanatory model,
      surgeons explicitly discussed limitations of the "fix-it" model as an independent
      rationale for operating as they deliberated about the value of surgery.
      CONCLUSIONS: Although the use of "fix-it" is familiar for explaining medical
      information to patients, surgeons recognize that the model can be problematic for
      determining the value of an operation. Whether patients can transition between
      understanding how their disease is fixed with surgery to a subsequent
      deliberation about whether they should have surgery is unclear and may have
      broader implications for surgical decision making.

PMID- 25749397
TI  - Edward Bermingham and the archives of clinical surgery: America's First Surgical
      Journal.
AB  - OBJECTIVE: To explore the life of Edward J. Bermingham (1853-1922) and his
      founding, in 1876, of the Archives of Clinical Surgery, the nation's first
      surgical journal. BACKGROUND: Beginning in the 1870s, American medicine found
      itself in the middle of a revolution marked by fundamental economic, scientific,
      and social transformations. For those physicians who wanted to be regarded as
      surgeons, the push toward specialization was foremost among these changes. The
      rise of surgery as a specialty was accomplished through various new initiatives;
      among them was the development of dedicated literature in the form of specialty
      journals to disseminate news of surgical research and technical innovations in a
      timely fashion. METHODS: An analysis of the published medical and lay literature
      and unpublished documents relating to Edward J. Bermingham and the Archives of
      Clinical Surgery. RESULTS: At a time when surgery was not considered a separate
      branch of medicine but a mere technical mode of treatment, Bermingham's
      publication of the Archives of Clinical Surgery was a milestone event in the
      ensuing rise of surgery as a specialty within the whole of medicine. CONCLUSIONS:
      The long forgotten Archives of Clinical Surgery provides a unique window into the
      world of surgery, as it existed when the medical revolution and the process of
      specialization were just beginning. For this reason, the Archives is among the
      more important primary resources with which to gain an understanding of
      prescientific surgery as it reached its endpoint in America.

PMID- 25749398
TI  - Theoretical investigation of thermodynamic stability and mobility of the
      intrinsic point defects in Ti3AC2 (A = Si, Al).
AB  - Nano-laminated Ti3AC2 (A = Si, Al) are highlighted as nuclear materials for a
      generation IV (GIV) reactor because they show high tolerance to radiation damage
      and remain crystalline under irradiation of high fluence heavy ions. In this
      paper, the energetics of formation and migration of intrinsic point defects are
      predicted by density functional theory calculations. We find that the space near
      the A atomic plane acts as a point defect sink and can accommodate lattice
      disorder. The migration energy barriers of Si/Al vacancy and TiSi anti-site
      defects along the atomic plane A are in the range of 0.3 to 0.9 eV, indicating
      their high mobility and the fast recovery of Si/Al Frenkel defects and Ti-A
      antisite pairs after irradiation. This layered structure induced large disorder
      accommodation and fast defect recovery must play an important role in the micro
      structural response of Ti3AC2 to irradiation. 

PMID- 25749399
TI  - African palm ethno-medicine.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: This study is the first to demonstrate the
      breadth and patterns of the medicinal applications of African palms. It sheds
      light on species with the potential to provide new therapeutic agents for use in
      biomedicine; and links the gap between traditional use of palms and
      pharmacological evaluation for the beneficial effects of palm products on human
      health. Last but not least, the study provides recommendations for the areas that
      should be targeted in future ethno-botanical surveys. AIM OF THE STUDY: The
      primary objective of this survey was to assemble all available ethno-medicinal
      data on African palms, and investigate patterns of palm uses in traditional
      medicine; and highlight possible under-investigated areas. MATERIALS AND METHODS:
      References were found through bibliographic searches using several sources
      including PubMed, Embase, and Google Scholar and search engines of the State and
      University Libraries of Aarhus, National Library of Denmark and Copenhagen
      University Libraries, Harvard University Libraries, and the Mertz Library.
      Information about ethno-medicinal uses of palms was extracted and digitized in a
      database. Additionally, we used an African palm distribution database to compute
      the proportion of palm species that have been used for medicinal purposes in each
      country. RESULTS: We found 782 medicinal uses mentioned in 156 references. At
      least 23 different palm species (some remained unidentified) were used
      medicinally in 35 out of Africa's 48 countries. The most commonly used species
      were Elaeis guineensis, Phoenix dactylifera, Cocos nucifera, and Borassus
      aethiopum. Medicinal uses were in 25 different use categories of which the most
      common ones were Infections/Infestations and Digestive System Disorders. Twenty
      four different parts of the palms were used in traditional medicine, with most of
      the uses related to fruit (and palm oil), root, seed and leaf. Palms were used in
      traditional medicine mostly without being mixed with other plants, and less
      commonly in mixtures, sometimes in mixture with products of animal origin. Future
      ethno-botanical surveys should be directed at the central African region, because
      palm species richness (and plant species richness in general) is particularly
      high in this area, and only few ethno-botanical studies available have focused on
      this region. CONCLUSION: The wide time span covered by our database (3500 years)
      shows that African palms have been used medicinally by many societies across the
      continent from time immemorial until today. Most medicinal use records for
      African palms were found in two categories that relate to most prevailing
      diseases and disorders in the region. By analyzing ethno-medicinal studies in one
      database we were able to demonstrate the value of palms in traditional medicine,
      and provide recommendations for the areas that should be targeted in future ethno
      botanical surveys.

PMID- 25749401
TI  - Intentional gestural communication and discrimination of human attentional states
      in rhesus macaques (Macaca mulatta).
AB  - The present study tested intentionality of a learned begging gesture and
      attention-reading abilities in rhesus macaques (Macaca mulatta). Subjects were
      trained to produce a begging gesture towards a hidden food reward that could be
      delivered by a human experimenter. More specifically, we investigated which
      attentional cues--body, face and/or eyes orientation of a human partner--were
      taken into account by the macaques in order to communicate with her. Our results
      provide strong evidence of intentional communication: the monkeys adjusted their
      behaviour to that of the partner. The latter's attentional state influenced the
      monkeys' likelihood of performing begging gestures and showing gaze alternation
      between the partner and the hidden food. By contrast, we found no evidence of
      attention-getting behaviours, persistence or elaboration of new communicative
      behaviours. Our results also showed that rhesus macaques discriminated gross cues
      including the presence, body and face orientation of the human experimenter but
      not her eyes. However, the monkeys emitted more gaze alternation and monitored
      the human's attentional state more closely when she also displayed gaze
      alternation, suggesting an important role of joint attention in gestural
      communication.

PMID- 25749400
TI  - Metabolomic identification of biochemical changes induced by fluoxetine and
      imipramine in a chronic mild stress mouse model of depression.
AB  - Metabolomics was applied to a C57BL/6N mouse model of chronic unpredictable mild
      stress (CMS). Such mice were treated with two antidepressants from different
      categories: fluoxetine and imipramine. Metabolic profiling of the hippocampus was
      performed using gas chromatography-mass spectrometry analysis on samples prepared
      under optimized conditions, followed by principal component analysis, partial
      least squares-discriminant analysis, and pair-wise orthogonal projections to
      latent structures discriminant analyses. Body weight measurement and behavior
      tests including an open field test and the forced swimming test were completed
      with the mice as a measure of the phenotypes of depression and antidepressive
      effects. As a result, 23 metabolites that had been differentially expressed among
      the control, CMS, and antidepressant-treated groups demonstrated that amino acid
      metabolism, energy metabolism, adenosine receptors, and neurotransmitters are
      commonly perturbed by drug treatment. Potential predictive markers for treatment
      effect were identified: myo-inositol for fluoxetine and lysine and oleic acid for
      imipramine. Collectively, the current study provides insights into the molecular
      mechanisms of the antidepressant effects of two widely used medications. 

PMID- 25749402
TI  - Cerebral amyloid angiopathy-associated microbleed mimicking transient ischemic
      attack.

PMID- 25749403
TI  - Lost in Translation: Physician Understanding and Communication of Risk to
      Patients With Possible Acute Coronary Syndrome Is Unacceptable and in Dire Need
      of Resuscitation.

PMID- 25749404
TI  - Choosing Analgesics Wisely: What We Know (and Still Need to Know) About Long-Term
      Consequences of Opioids.

PMID- 25749405
TI  - Versatility of Streptomyces sp. M7 to bioremediate soils co-contaminated with
      Cr(VI) and lindane.
AB  - The aim of this work was to study the impact of environmental factors on the
      bioremediation of Cr(VI) and lindane contaminated soil, by an actinobacterium,
      Streptomyces sp. M7, in order to optimize the process. Soil samples were
      contaminated with 25 ug kg(-1) of lindane and 50 mg kg(-1) of Cr(VI) and
      inoculated with Streptomyces sp. M7. The lowest inoculum concentration which
      simultaneously produced highest removal of Cr(VI) and lindane was 1 g kg(-1). The
      influence of physical and chemical parameters was assessed using a full factorial
      design. The factors and levels tested were: Temperature: 25, 30, 35 degrees C;
      Humidity: 10%, 20%, 30%; Initial Cr(VI) concentration: 20, 50, 80 mg kg(-1);
      Initial lindane concentration: 10, 25, 40 ug kg(-1). Streptomyces sp. M7
      exhibited strong versatility, showing the ability to bioremediate co-contaminated
      soil samples at several physicochemical conditions. Streptomyces sp. M7 inoculum
      size was optimized. Also, it was fitted a model to study this process, and it was
      possible to predict the system performance, knowing the initial conditions.
      Moreover, optimum temperature and humidity conditions for the bioremediation of
      soil with different concentrations of Cr(VI) and lindane were determined. Lettuce
      seedlings were a suitable biomarker to evaluate the contaminants mixture
      toxicity. Streptomyces sp. M7 carried out a successful bioremediation, which was
      demonstrated through ecotoxicity test with Lactuca sativa.

PMID- 25749406
TI  - Physician review websites: effects of the proportion and position of negative
      reviews on readers' willingness to choose the doctor.
AB  - Health consumers are increasingly turning to physician review websites to
      research potential health care providers. This experiment examined how the
      proportion and position of negative reviews on such websites influence readers'
      willingness to choose the reviewed physician. A 5 * 2 (Proportion of Negative
      Reviews * Position of Negative Reviews) factorial design was implemented,
      augmented with two standalone comparison groups. Five hundred participants were
      recruited through a crowdsource website and were randomly assigned to read a
      webpage screenshot corresponding to 1 of 12 experimental conditions. The
      participants then completed a questionnaire that assessed evaluations of and
      cognitive elaborations (thoughts) about the physician. The authors hypothesized
      that readers would be less willing to use a physician's services when reviews
      were predominantly negative and negative comments were positioned before positive
      comments. As hypothesized, an increase in the proportion of negative reviews led
      to a reduced willingness to use the physician's services. However, this effect
      was not moderated by the level of cognitive elaboration. A primacy effect was
      found for negative reviews such that readers were less willing to use the
      physician's services when negative reviews were presented before positive
      reviews, rather than after. Implications for future research are discussed. 

PMID- 25749407
TI  - Hypermethylated ERG as a cell-free fetal DNA biomarker for non-invasive prenatal
      testing of Down syndrome.
AB  - BACKGROUND: Previous reports have shown that the ERG gene is hypermethylated in
      the placenta and hypomethylated in maternal blood cells. In this study, we
      explore the feasibility of hypermethylated ERG as a cell-free fetal (cff) DNA
      biomarker for non-invasive prenatal testing (NIPT) of Down syndrome. METHODS: We
      randomly selected 90 healthy pregnant women, including 30 cases at each trimester
      of pregnancy. In addition, 15 pregnant women were recruited as the case group
      whose fetuses had been confirmed to have trisomy 21 by amniotic fluid analysis at
      18th to 26th week gestation. Using HpaII, MspI to digest cell-free maternal
      plasma DNA, we performed SYBR Green PCR to detect methylated sites of ERG
      sequences, and analyzed the concentrations of cff DNA in maternal plasma in
      different gestational trimesters and the case group. RESULTS: The ERG median
      concentrations of the maternal plasma after Hpa II digestion (LG copies/ml) in
      first, second and third-trimesters were 5.38, 6.10, and 7.04, respectively
      (Kruskal-Wallis, P<0.01); and that in the trisomy 21 case group was 6.85, which
      was higher than the second-trimester (Mann-Whitney, P<0.01). CONCLUSIONS: The
      study demonstrated that ERG gene is hypermethylated in cff DNA but hypomethylated
      in maternal DNA; and the median concentration of ERG gene in the trisomy 21 case
      group is higher than that in the gestational trimester matched normal group. ERG
      gene, as a fetal DNA biomarker, may be useful for NIPT of Down syndrome.

PMID- 25749408
TI  - Neonatal infections due to multi-resistant strains: Epidemiology, current
      treatment, emerging therapeutic approaches and prevention.
AB  - Severe infections represent the main cause of neonatal mortality accounting for
      more than one million neonatal deaths worldwide every year. Antibiotics are the
      most commonly prescribed medications in neonatal intensive care units. The
      benefits of antibiotic therapy when indicated are clearly enormous, but the
      continued and widespread use of antibiotics has generated over the years a strong
      selective pressure on microorganisms, favoring the emergence of resistant
      strains. Health agencies worldwide are galvanizing attention toward antibiotic
      resistance in gram-positive and gram-negative bacteria. Infections in neonatal
      units due to multidrug and extensively multidrug resistant bacteria are rising
      and are already seriously challenging antibiotic treatment options. While there
      is a growing choice of agents against multi-resistant gram-positive bacteria, new
      options for multi-resistant gram-negative bacteria in the clinical practice have
      decreased significantly in the last 20 years making the treatment of infections
      caused by multidrug-resistant pathogens challenging mostly in neonates. Treatment
      options are currently limited and will be some years before any new treatment for
      neonates become available for clinical use, if ever. The aim of the review is to
      highlight the current knowledge on antibiotic resistance in the neonatal
      population, the possible therapeutic choices, and the prevention strategies to
      adopt in order to reduce the emergency and spread of resistant strains.

PMID- 25749409
TI  - Isolation and structure determination of new siderophore albachelin from
      Amycolatopsis alba.
AB  - A new siderophore named albachelin was isolated from iron deficient culture of
      Amycolatopsis alba. The planar structure of albachelin was elucidated by the
      combination of ESI-MS/MS experiment and NMR spectroscopic analyses of the gallium
      (III) complex. The structure of albachelin was determined to be a linear peptide
      consisting of 6 mol of amino acids including 3 mol of serine, one mol each of N
      alpha-acethyl-N-delta-hydroxy-N-delta-formylornithine, N-alpha-methyl-N-delta
      hydroxyornithine, and cyclic N-hydroxyornithine. The stereochemistries of amino
      acids constituting albachelin were analyzed by applying modified Marfey method to
      the hydrolysate of albachelin. Based on bioinformatics, we deduced and discussed
      the possible biosynthetic gene cluster involved in albachelin biosynthesis from
      the genome sequence of A. alba. By prediction of substrates for adenylation
      domains, a non-ribosomal peptide biosynthetase gene (AMYAL_RS0130210) was
      proposed to be the main biosynthetic gene for albachelin biosynthesis. The
      related genes including transporter for siderophore were found near the NRPS gene
      as a gene cluster.

PMID- 25749410
TI  - [Expectations of patients with ovarian cancer. Results of the European
      investigation EXPRESSION III in French patients from GINECO group].
AB  - EXPRESSION III was designed to evaluate the information, needs and expectations
      of patients with ovarian cancer in different European countries. This abstract
      focuses on specific results from French OC patients. Two hundred and fifty-seven
      patients filled a 27-item questionnaire during a medical visit. Median age range
      was 63 years (26-89). Nearly all the patients (94 %) had primary surgery and
      adjuvant chemotherapy (95 %), 50 % had recurrent disease. At the time of the
      survey, 85 % reported symptoms: fatigue: 88 %, neuropathy: 55 %, nausea/vomiting:
      40 %, pain: 39 %. Patients wished for non-alopeciant treatment (52 %) and a
      better management of fatigue (42 %). Eighty percent of the patients knew their
      chemotherapy but 60 % ignored their initial disease stage and how to find more
      information for treatment choice (91 %). Most patients (92 %) preferred to get it
      directly from their physician. Sixty-six percent expressed the need for clear
      information about their life expectancy. Still 21 % patients did not want to get
      negative information. French patients need for more support and clearer
      information on their disease. Direct information from their physician remains the
      mainstay of communication. 

PMID- 25749411
TI  - Molecular characterization of Cryptosporidium spp. among children in rural Ghana.
AB  - BACKGROUND: The relevance of Cryptosporidium infections for the burden of
      childhood diarrhoea in endemic settings has been shown in recent years. This
      study describes Cryptosporidium subtypes among symptomatic and asymptomatic
      children in rural Ghana to analyse subtype-specific demographic, geographical,
      seasonal and clinical differences in order to inform appropriate control measures
      in endemic areas. METHODOLOGY/PRINCIPAL FINDINGS: Stool samples were collected
      from 2232 children below 14 years of age presenting with and without
      gastrointestinal symptoms at the Agogo Presbyterian Hospital in the rural Ashanti
      region of Ghana between May 2007 and September 2008. Samples were screened for
      Cryptosporidium spp. by PCR and isolates were classified into subtypes based on
      sequence differences in the gp60 gene. Subtype specific frequencies for age, sex,
      location and season have been determined and associations with disease symptoms
      have been analysed within a case-control study. Cryptosporidium infections were
      diagnosed in 116 of 2232 (5.2%) stool samples. Subtyping of 88 isolates revealed
      IIcA5G3 (n = 26, 29.6%), IbA13G3 (n = 17, 19.3%) and IaA21R3 (n = 12, 13.6%) as
      the three most frequent subtypes of the two species C. hominis and C. parvum,
      known to be transmitted anthroponotically. Infections peak at early rainy season
      with 67.9% and 50.0% of infections during the months April, May and June for 2007
      and 2008 respectively. C. hominis infection was mainly associated with diarrhoea
      (odds ratio [OR] = 2.4; 95% confidence interval [CI]: 1.2-4.9) whereas C. parvum
      infection was associated with both diarrhoea (OR = 2.6; CI: 1.2-5.8) and vomiting
      (OR = 3.1; 95% CI: 1.5-6.1). CONCLUSIONS/SIGNIFICANCE: Cryptosporidiosis is
      characterized by seasonal anthroponotic transmission of strains typically found
      in Sub-Saharan Africa. The infection mainly affects young infants, with vomiting
      and diarrhoea being one of the leading symptoms in C. parvum infection. Combining
      molecular typing and clinical data provides valuable information for physicians
      and is able to track sources of infections.

PMID- 25749413
TI  - More than one in two venous thromboembolism treated in French hospitals occurs
      during the hospital stays.
AB  - OBJECTIVE: The objective was to describe the prevalence of venous
      thromboembolism, pulmonary embolism, and deep vein thrombosis among hospitalized
      patients and the percentages of those occurring during the hospital stays.
      METHODS: French DRG gave now the opportunity to investigate the frequency of
      venous thromboembolism occurring during the hospital stay. Statistics are issued
      from the national PMSI MCO databases encoded using the CIM10. Since 2010-2011 it
      is possible to differentiate the reason for hospital admission from the
      pathologies which secondly occurred. Any stay with the ICD-10 codes selected was
      considered as a hospital-occurred thrombosis unless it was the principal
      diagnosis of the first medical unit summary. To eliminate outpatient
      consultations or in day care, stays of <48 h were excluded. RESULTS: The results
      pertain to the 78,838,983 hospitalizations in France from 2005 to 2011 and on the
      18,683,603 hospital stays in 2010-2011. The incidence of hospital stays came to
      860,343 (1.09%) for venous thromboembolism, with 428,261 (0.543%) for deep vein
      thrombosis without pulmonary embolism and 432,082 (0.548%) for pulmonary
      embolism. It corresponds to an incidence of 189 per 100,000 inhabitants. Out of
      100 hospital stays involving venous thromboembolism, for 40.3% venous
      thromboembolism was the cause of hospitalization whereas 59.7% can be considered
      to have occurred during hospital stay. These distributions are of 25.6 and 74.4%
      for deep vein thrombosis, respectively, 53.8 and 46.2% for pulmonary embolism.
      CONCLUSION: The high proportion of hospital-occurred venous thromboembolism is an
      alarming situation that should question the quality of prevention and/or its
      effectiveness.

PMID- 25749414
TI  - Vitamin D as an adjunctive therapy in asthma. Part 2: A review of human studies.
AB  - Vitamin D deficiency (VDD) is highly prevalent worldwide, with adverse effects on
      bone health but also potentially other unfavorable consequences. VDD and asthma
      incidence/severity share many common risk factors, including winter season,
      industrialization, poor diet, obesity, dark skin pigmentation, and high latitude.
      Multiple anatomical areas relevant to asthma contain both the enzyme responsible
      for producing activated vitamin D and the vitamin D receptor suggesting that
      activated vitamin D (1,25-dihydroxyvitamin D) may have important local effects at
      these sites. Emerging evidence suggests that VDD is associated with increased
      airway hyperresponsiveness, decreased pulmonary function, worse asthma control,
      and possibly decreased response to standard anti-asthma therapy. However the
      effect is inconsistent with preliminary evidence from different studies
      suggesting vitamin D is both beneficial and detrimental to asthma genesis and
      severity. Current evidence suggests that supplementation with moderate doses of
      vitamin D may be appropriate for maintenance of bone health in asthmatics,
      particularly steroid users. However emerging data from an increasing number of
      randomized, controlled, intervention studies of vitamin D supplementation in
      pediatric and adult asthma are becoming available and should help determine the
      importance, if any of vitamin D for asthma pathogenesis. The purpose of this
      second of a two-part review is to review the current human literature on vitamin
      D and asthma, discussing the possible consequences of VDD for asthma and the
      potential for vitamin D repletion as adjunct therapy. 

PMID- 25749412
TI  - PIM kinase (and Akt) biology and signaling in tumors.
AB  - The initiation and progression of human cancer is frequently linked to the
      uncontrolled activation of survival kinases. Two such pro-survival kinases that
      are commonly amplified in cancer are PIM and Akt. These oncogenic proteins are
      serine/threonine kinases that regulate tumorigenesis by phosphorylating
      substrates that control the cell cycle, cellular metabolism, proliferation, and
      survival. Growing evidence suggests that cross-talk exists between the PIM and
      Akt kinases, indicating that they control partially overlapping survival
      signaling pathways that are critical to the initiation, progression, and
      metastatic spread of many types of cancer. The PI3K/Akt signaling pathway is
      activated in many human tumors, and it is well established as a promising
      anticancer target. Likewise, based on the role of PIM kinases in normal and tumor
      tissues, it is clear that this family of kinases represents an interesting target
      for anticancer therapy. Pharmacological inhibition of PIM has the potential to
      significantly influence the efficacy of standard and targeted therapies. This
      review focuses on the regulation of PIM kinases, their role in tumorigenesis, and
      the biological impact of their interaction with the Akt signaling pathway on the
      efficacy of cancer therapy. 

PMID- 25749415
TI  - Antimicrobial resistance, virulence factors and genetic lineages of hospital
      onset methicillin-resistant Staphylococcus aureus isolates detected in a hospital
      in Zaragoza.
AB  - INTRODUCTION: MRSA population dynamics is undergoing significant changes, and for
      this reason it is important to know which clones are circulating in our
      nosocomial environment. MATERIALS AND METHODS: A total of 118 MRSA isolates were
      collected from clinical samples from patients with previous hospital or
      healthcare contact (named as hospital-onset MRSA (HO-MRSA)) during a one year
      period. Susceptibility testing was performed by disk diffusion and microdilution.
      The presence of resistance genes and virulence factors were tested by PCR. All
      isolates were typed by SCCmec, spa and agr typing. PFGE and MLST were applied to
      a selection of them. RESULTS: Eighty-three HO-MRSA isolates (70.3%) were
      resistant to any antibiotic included in the macrolide-lincosamide-streptogramin B
      group. Among these isolates, the M phenotype was the most frequent (73.5%). One
      hundred and seven of HO-MRSA isolates (90.7%) showed aminoglycoside resistance.
      The combination aac(6')-Ie-aph(2")-Ia+ant(4')-Ia genes was the most frequent
      (22.4%). Tetracycline resistance rates in HO-MRSA isolates were low (3.4%),
      although a high level of mupirocin resistance was observed (25.4%). Most of the
      HO-MRSA isolates (approximately 90%) showed SCCmec type IVc and agr type II.
      Fifteen unrelated pulsotypes were identified. CC5 was the most prevalent (88.1%),
      followed by CC8 (5.9%), CC22 (2.5%), CC398 (2.5%) and CC1 (0.8%). CONCLUSION:
      CC5/ST125/t067 lineage was the most frequent. This lineage was related to
      aminoglycoside resistance, and to a lesser extent, with macrolide resistance. The
      presence of international clones as EMRSA-15 (CC22/ST22), European clones as
      CC5/ST228, community clones related to CC1 or CC8 and livestock associated
      clones, as CC398, were observed in a low percentage.

PMID- 25749416
TI  - Cost/efficacy analysis of preferred Spanish AIDS study group regimens and the
      dual therapy with lopinavir/ritonavir plus lamivudine for initial ART in HIV
      infected adults.
AB  - INTRODUCTION: The National AIDS Plan and the Spanish AIDS study group (GESIDA)
      proposes "preferred regimens" (PR) of antiretroviral treatment (ART) as initial
      therapy in HIV-infected patients. In 2013, the recommended regimens were all
      triple therapy regimens. The Gardel Study assessed the efficacy of a dual therapy
      (DT) combination of lopinavir/ritonavir (LPV/r) plus lamivudine (3TC). Our
      objective is to evaluate the GESIDA PR and the DT regimen LPV/r+3TC cost/efficacy
      ratios. METHODS: Decision tree models were built. EFFICACY: probability of having
      viral load <50 copies/mL at week 48. ART regime cost: costs of ART, adverse
      effects, and drug resistance tests during the first 48 weeks. RESULTS:
      Cost/efficacy ratios varied between 5,817 and 13,930 euros per responder at 48
      weeks, for the DT of LPV/r+3TC and tenofovir DF/emtricitabine+raltegravir,
      respectively. CONCLUSIONS: Taking into account the official Spanish prices of
      ART, the most efficient regimen was DT of LPV/r+3TC, followed by the triple
      therapy with non-nucleoside containing regimens.

PMID- 25749417
TI  - Bevacizumab increases the risk of infections in cancer patients: A systematic
      review and pooled analysis of 41 randomized controlled trials.
AB  - BACKGROUND: Bevacizumab, a recombinant humanized monoclonal antibody that targets
      the vascular endothelial growth factor, has been approved for use in a variety of
      malignancies. There have been reports of infections associated with the use of
      bevacizumab. We performed this meta-analysis to determine the overall incidence
      and risk of infections associated with bevacizumab in cancer patients. METHODS:
      Pubmed and oncology conference proceedings were searched for relevant studies
      from January 2000 to June 2014. Studies were limited to phase II and phase III
      randomized controlled trials (RCTs) of bevacizumab in cancer patients with
      adequate safety profiles. Summary incidences, relative risks (RRs), and 95%
      confidence intervals (95%CIs) were calculated by using either random effects or
      fixed effect models according to the heterogeneity of included studies. RESULTS:
      In total 33,526 patients from 41 RCTs were included. The use of bevacizumab
      significantly increased the risk of developing all-grade (RR 1.45, 95%CI: 1.27
      1.66, p<0.001) and high-grade (RR 1.59, 95%CI: 1.42-1.79, p<0.001) infections in
      cancer patients. Sensitivity analysis indicated that the significance estimate of
      pooled RRs was not significantly influenced by omitting any single study. On
      subgroup analysis, the risk of developing high-grade infection varied
      significantly with concomitant drugs (p=0.008). When stratified according to
      specific infectious events, the use of bevacizumab significantly increased the
      risk of developing severe febrile neutropenia (RR 1.57, 95%CI: 1.34-1.84;
      p<0.001) and fistulae/abscesses (RR 2.13, 95%CI: 1.06-4.27; p=0.033). No evidence
      of publication bias was observed. CONCLUSIONS: Bevacizumab treatment
      significantly increases the risk of infectious events developing in cancer
      patients. The risk may vary with concomitant drugs. Clinicians should be aware of
      the risks of infections with the administration of this drug in cancer patients.

PMID- 25749418
TI  - [In time: human milk is the feeding strategy to prevent necrotizing
      enterocolitis].

PMID- 25749419
TI  - Triapine-mediated ABCB1 induction via PKC induces widespread therapy
      unresponsiveness but is not underlying acquired triapine resistance.
AB  - Although triapine is promising for treatment of advanced leukemia, it failed
      against solid tumors due to widely unknown reasons. To address this issue, a new
      triapine-resistant cell line (SW480/tria) was generated by drug selection and
      investigated in this study. Notably, SW480/tria cells displayed broad cross
      resistance against several known ABCB1 substrates due to high ABCB1 levels
      (induced by promoter hypomethylation). However, ABCB1 inhibition did not re
      sensitize SW480/tria cells to triapine and subsequent analysis revealed that
      triapine is only a weak ABCB1 substrate without significant interaction with the
      ABCB1 transport function. Interestingly, in chemo-naive, parental SW480 cells
      short-time (24 h) treatment with triapine stimulated ABCB1 expression. These
      effects were based on activation of protein kinase C (PKC), a known response to
      cellular stress. In accordance, SW480/tria cells were characterized by elevated
      levels of PKC. Together, this led to the conclusion that increased ABCB1
      expression is not the major mechanism of triapine resistance in SW480/tria cells.
      In contrast, increased ABCB1 expression was found to be a consequence of triapine
      stress-induced PKC activation. These data are especially of importance when
      considering the choice of chemotherapeutics for combination with triapine.

PMID- 25749420
TI  - Autophagy contributes to the enrichment and survival of colorectal cancer stem
      cells under oxaliplatin treatment.
AB  - Currently, chemoresistance is an important cause of treatment failure in
      colorectal cancer. Cancer stem cells, which are a population of multi-potent
      cells with the capacity to self-renew and differentiate, have been found to
      participate in chemoresistance. In the present study, the chemotherapeutic drug
      oxaliplatin induced autophagy in colorectal cancer cell lines, which in turn
      protected cancer cells from apoptosis. Further results showed that oxaliplatin
      induced autophagy enriched the population of colorectal CSCs and participated in
      maintaining the stemness of colorectal CSCs, thus making the cells more resistant
      to chemotherapy. Taken together, the results indicate that autophagy might
      enhance the chemoresistance of colorectal cancer cells by protecting the stemness
      and chemoresistance of colorectal CSCs. Our study demonstrates that autophagy
      plays a pro-survival role in colorectal CSCs subjected to oxaliplatin. Therefore,
      targeting autophagy may be considered as a potential therapeutic strategy to
      address chemoresistance in the treatment of colorectal cancer.

PMID- 25749421
TI  - A feedback regulation between miR-145 and DNA methyltransferase 3b in prostate
      cancer cell and their responses to irradiation.
AB  - It is believed that epigenetic modification plays roles in cancer initiation and
      progression. Both microRNA and DNA methyltransferase are epigenetic regulation
      factors. It was found that miR-145 upregulates while DNMT3b downregulates in PC3
      cells. Presence of any negative correlationship and their response to irradiation
      were investigated in the current study. We found that miR-145 downregulated
      DNMT3b expression by directly targeting the 3'-UTR of DNMT3b mRNA and knockdown
      of DNMT3b increased expression of miR-145 via CpG island promoter
      hypomethylation, suggesting that there is a crucial crosstalk between miR-145 and
      DNMT3b via a double-negative feedback loop. Responses of the miR-145 and DNMT3b
      to irradiation are a negative correlation. We also found that either
      overexpression of miR-145 or knockdown of DNMT3b sensitized prostate cancer cells
      to X-ray radiation. Our findings enrich the complex relationships between miRNA
      and DNMTs in carcinogenesis and irradiation stress. It also sheds light on the
      potential combination of ionizing radiation and epigenetic regulation in prostate
      cancer therapy.

PMID- 25749422
TI  - WP1130 increases doxorubicin sensitivity in hepatocellular carcinoma cells
      through usp9x-dependent p53 degradation.
AB  - Resistance to chemotherapeutic drugs is a major obstacle in hepatocellular
      carcinoma (HCC) therapy. However, the underlying mechanisms are not well
      understood. Recent evidence suggests that deubiquitinases (DUB) are key
      regulators in the mechanisms of cell proliferation, apoptosis and
      chemoresistance. The present study aimed to investigate whether WP1130, which
      inhibits activity of deubiquitinases, exerts synergistic cytotoxicity with
      doxorubicin in HCC and the underlying mechanisms. In the study, we found that
      Huh7, HepG2, and SNU387 HCC cells with p53 expression displayed enhanced response
      to the combination therapy compared with p53-deficient HCC cells (Hep3B) in the
      manner of inhibiting cell proliferation. Downregulation of p53 abolished the
      synergistic cytotoxicity of doxorubicin and WP1130 on HCC cells. Mechanistically,
      we found that combined treatment with WP1130 suppressed doxorubicin-mediated
      upregulation of p53 via promoting its ubiquitin-proteasome dependent degradation,
      whereas knockdown of DUB usp9x abolished this effect. Taken together, these
      results demonstrate that combined treatment with WP1130 sensitized HCC cells to
      doxorubicin via usp9x-depedent p53 degradation. 

PMID- 25749424
TI  - Monkeys pass the mirror test after training.

PMID- 25749423
TI  - Therapeutic potential of berberine against neurodegenerative diseases.
AB  - Berberine (BBR) is an organic small molecule isolated from various plants that
      have been used in traditional Chinese medicine. Isolation of this compound was
      its induction into modern medicine, and its usefulness became quickly apparent as
      seen in its ability to combat bacterial diarrhea, type 2 diabetes,
      hypercholesterolemia, inflammation, heart diseases, and more. However, BBR's
      effects on neurodegenerative diseases remained relatively unexplored until its
      ability to stunt Alzheimer's disease (AD) progression was characterized. In this
      review, we will delve into the multi-faceted defensive capabilities and bio
      molecular pathways of BBR against AD, Parkinson's disease (PD), and trauma
      induced neurodegeneration. The multiple effects of BBR, some of which enhance
      neuro-protective factors/pathways and others counteract targets that induce
      neurodegeneration, suggest that there are many more branches to the diverse
      capabilities of BBR that have yet to be uncovered. The promising results seen
      provide a convincing and substantial basis to support further scientific
      exploration and development of the therapeutic potential of BBR against
      neurodegenerative diseases. 

PMID- 25749425
TI  - COLD1: a cold sensor in rice.

PMID- 25749426
TI  - Plasmon-plasmon hybridization and bandwidth enhancement in nanostructured
      graphene.
AB  - Graphene plasmonic structures with long-range layering periodicity are presented.
      Resonance energy scaling with the number of graphene layers involved in plasmonic
      excitation allows these structures to support multiple plasmonic modes that
      couple and hybridize due to their physical proximity. Hybridized states exhibit
      bandwidth enhancements of 100-200% compared to unhybridized modes, and resonance
      energies deviate from what is usually observed in coupled plasmonic systems.
      Origins of this behavior are discussed, and experimental observations are
      computationally modeled. This work is a precursor and template for the study of
      plasmonic hybridization in other two-dimensional material systems with layering
      periodicity. 

PMID- 25749427
TI  - Letter to the editor concerning the review of Prof. Sheldon L. Kaplan "Recent
      lessons for the management of bone and joint infections"--Bacteriostatic or
      bactericidal agents in osteoarticular infections?

PMID- 25749428
TI  - Duty to Inform and Informed Consent in Diagnostic Radiology: How Ethics and Law
      can Better Guide Practice.
AB  - Although there is consensus on the fact that ionizing radiation used in
      radiological examinations can affect health, the stochastic (random) nature of
      risk makes it difficult to anticipate and assess specific health implications for
      patients. The issue of radiation protection is peculiar as any dosage received in
      life is cumulative, the sensitivity to radiation is highly variable from one
      person to another, and between 20 % and 50 % of radiological examinations appear
      not to be necessary. In this context, one might reasonably assume that
      information and patient consent would play an important role in regulating
      radiological practice. However, there is to date no clear consensus regarding the
      nature and content of-or even need for-consent by patients exposed to ionizing
      radiation. While law and ethics support the same principles for respecting the
      dignity of the person (inviolability and integrity), in the context of radiology
      practice, they do not provide a consistent message to guide clinical decision
      making. This article analyzes the issue of healthcare professionals' duty to
      inform and obtain patient consent for radiological examinations. Considering that
      both law and ethics have as one of their aims to protect vulnerable populations,
      it is important that they begin to give greater attention to issues raised by the
      use of ionizing radiation in medicine. While the situation in Canada serves as a
      backdrop for a reflective analysis of the problem, the conclusions are pertinent
      for professional practice in other jurisdictions because the principles
      underlying health law and jurisprudence are fairly general. 

PMID- 25749429
TI  - [Rehabilitation after polytrauma : Definitions and treatment approaches].
AB  - After initial resuscitation and surgical reconstruction of structural damages,
      the functional rehabilitation is one of the critical columns of polytraumatized
      patient management. This programme starts as early as the initial therapy in the
      trauma bay and proceeds until socio-professional reintegration of the patient
      into his pre-traumatic environment.Thus, three phases of a rehabilitation were
      identified: the early rehabilitation, the post-acute rehabilitation and the
      continuative rehabilitation.Since the mortality after major trauma is
      continuously decreasing, the life quality of trauma victims came more and more
      into the focus of the actual scientific discussion. To improve this life quality,
      several rehabilitation programmes were developed and varius instruments were
      developed to quantify outcome results, such as the GOS or the SF-36,
      respectively.The aim of this review is to describe these various programmes and
      instruments, to improve the individual rehabilitation process for polytraumatized
      patients. 

PMID- 25749430
TI  - [Knee laxity in anterior cruciate ligament reconstruction : The influence of
      graft rotation using interference screw fixation].
AB  - BACKGROUND: The use of interference screws for femoral graft fixation in anterior
      cruciate ligament (ACL) reconstruction with hamstring grafts can result in
      rotation of the graft around the screw leading to changes in the final position
      of the graft within the bone tunnel. MATERIAL AND METHODS: In a prospective study
      107 patients (54 right and 53 left knees) underwent ACL reconstruction with a
      hamstring tendon autograft. Femoral fixation of the graft was performed with a
      standard right-thread screw in all cases. Patients were assessed at 6 months
      postoperatively with the international knee documentation committee (IKDC)
      standard evaluation including instrumented laxity measurements and the results
      were compared between right and left knees. RESULTS: A significantly higher
      postoperative anterior laxity was observed in left knees with a negative Lachman
      test in only 64 % of the cases compared with 87 % in the group of right knees.
      Accordingly, instrumented laxity measurements of the reconstructed knee compared
      with the contralateral knee revealed significant differences between left and
      right knees (left knees 1.8+/-1.2 mm and right knees 1.0+/-1.4 mm). CONCLUSIONS:
      This study demonstrates the importance of femoral graft positioning and its
      sensitivity to multiple influencing factors. The use of standard right-thread
      interference screws for femoral graft fixation in the mirrored situation of right
      and left knees may produce a systematic error in ACL reconstruction. Due to a
      possible rotation of the graft around the screw, the final position of the
      transplant may vary thus leading to significant changes in anterior translation
      of the operated knee.

PMID- 25749431
TI  - Self-reported trait mindfulness and affective reactivity: a motivational approach
      using multiple psychophysiological measures.
AB  - As a form of attention, mindfulness is qualitatively receptive and non-reactive,
      and is thought to facilitate adaptive emotional responding. One suggested
      mechanism is that mindfulness facilitates disengagement from an affective
      stimulus and thereby decreases affective reactivity. However, mindfulness has
      been conceptualized as a state, intervention, and trait. Because evidence is
      mixed as to whether self-reported trait mindfulness decreases affective
      reactivity, we used a multi-method approach to study the relationship between
      individual differences in self-reported trait mindfulness and electrocortical,
      electrodermal, electromyographic, and self-reported responses to emotional
      pictures. Specifically, while participants (N = 51) passively viewed pleasant,
      neutral, and unpleasant IAPS pictures, we recorded high-density (128 channels)
      electrocortical, electrodermal, and electromyographic data to the pictures as
      well as to acoustic startle probes presented during the pictures. Afterwards,
      participants rated their subjective valence and arousal while viewing the
      pictures again. If trait mindfulness spontaneously reduces general emotional
      reactivity, then for individuals reporting high rather than low mindfulness,
      response differences between emotional and neutral pictures would show relatively
      decreased early posterior negativity (EPN) and late positive potential (LPP)
      amplitudes, decreased skin conductance responses, and decreased subjective
      ratings for valence and arousal. High mindfulness would also be associated with
      decreased emotional modulation of startle eyeblink and P3 amplitudes. Although
      results showed clear effects of emotion on the dependent measures, in general,
      mindfulness did not moderate these effects. For most measures, effect sizes were
      small with rather narrow confidence intervals. These data do not support the
      hypothesis that individual differences in self-reported trait mindfulness are
      related to spontaneous emotional responses during picture viewing. 

PMID- 25749432
TI  - An ERP Study of Causative Cleft Construction in Japanese: Evidence for the
      Preference of Shorter Linear Distance in Sentence Comprehension.
AB  - This study examined the processing of two types of Japanese causative cleft
      constructions (subject-gap vs. object-gap) by conducting an event-related brain
      potential experiment to clarify the processing mechanism of long-distance
      dependencies. The results demonstrated that the subject-gap constructions
      elicited larger P600 effects than the object-gap constructions. Based on these
      findings, we argue that the linear distance rather than the structural distance
      between the extracted argument (filler) and its original gap position is a
      crucial factor for determining processing costs of gap-filler dependency in
      Japanese causative cleft constructions. This argument indicates that (at least)
      some types of long-distance dependencies are sensitive to linear distance. 

PMID- 25749433
TI  - Missing relationship of moyamoya and persistent primitive artery in Europeans.
      Another distinctive feature or artifact?
AB  - PURPOSE: Previous studies found higher incidence of persistent primitive arteries
      in Asian moyamoya (MM) patients than in the general population, which was thought
      to be a characteristic trait of the MM entity in general. We analyzed incidence
      of persistent primitive arteries and demographics of patients with European MM
      treated in one single center. First, we compared our large dataset to existing
      literature and second, we raised the question whether European MM demonstrates
      similar high prevalence of persistent primitive arteries as it was previously
      presented within Asian MM. METHODS: All European MM on whom revascularization
      surgery was performed from 1999 to 2013 were included. Demographics and
      associated diseases were obtained by retrospective chart review. Two independent
      readers evaluated 122 MM angiograms to determine the occurrence of persistent
      primitive arteries as well as the Suzuki score. RESULTS: We identified 112 cases
      with MM disease, 10 with MM syndrome. Mean age at time of diagnosis was 38.2
      (range 6-64 years); a peak incidence in early childhood was not observed. Ninety
      (73.8%) were women, associated systemic diseases were found in four patients.
      Seven cases (5.7%) presented with unilaterally affected vessels. The majority of
      patients (71; 58.2%) were graded Suzuki Score 3. One 14-year-old boy with
      moyamoya presented with a primitive trigeminal artery (0.89%). CONCLUSIONS: We
      did not find a bimodal age distribution, but only a second peak during adulthood.
      Unlike previous studies on Asian moyamoya patients, our collective does not
      exhibit a higher prevalence of persistent primitive arteries than the normal
      population.

PMID- 25749434
TI  - Layer-by-layer assembly of multifunctional porous N-doped carbon nanotube hybrid
      architectures for flexible conductors and beyond.
AB  - Coassemble diverse functional nanomaterials with carbon nanotubes (CNTs) to form
      three-dimensional (3D) porous CNTs hybrid architectures (CHAs) are potentially
      desirable for applications in energy storage, flexible conductors, and catalysis,
      because of diverse functionalities and synergistic effects in the CHAs. Herein,
      we report a scalable strategy to incorporate various functional nanomaterials
      with N-doped CNTs (N-CNTs) into such 3D porous CHAs on the polyurethane (PU)
      sponge skeletons via layer-by-layer (LbL) assembly. To investigate their
      properties and applications, the specific CHAs based on N-CNTs and Ag
      nanoparticles (NPs), denoted as PU-(N-CNTs/Ag NPs)n, are developed. The unique
      binary structure enables these specific CHAs conductors to possess reliable
      mechanical and electrical performance under various elastic deformations as well
      as excellent hydrophilicity. Moreover, they are employed as strain-gauge sensor
      and heterogeneous catalyst, respectively. The sensor could detect continuous
      signal, static signal, and pulse signal with superior sustainability and
      reversibility, indicating an important branch of electromechanical devices.
      Furthermore, the synergistic effects among N-CNTs, Ag NPs, and porous structure
      endow the CHAs with excellent performance in catalysis. We have a great
      expectation that LbL assembly can afford a universal route for incorporating
      diverse functional materials into one structure. 

PMID- 25749435
TI  - Cell-based bone regeneration for alveolar ridge augmentation--cell source,
      endogenous cell recruitment and immunomodulatory function.
AB  - Alveolar ridge plays a pivotal role in supporting dental prosthesis particularly
      in edentulous and semi-dentulous patients. However the alveolar ridge undergoes
      atrophic change after tooth loss. The vertical and horizontal volume of the
      alveolar ridge restricts the design of dental prosthesis; thus, maintaining
      sufficient alveolar ridge volume is vital for successful oral rehabilitation.
      Recent progress in regenerative approaches has conferred marked benefits in
      prosthetic dentistry, enabling regeneration of the atrophic alveolar ridge. In
      order to achieve successful alveolar ridge augmentation, sufficient numbers of
      osteogenic cells are necessary; therefore, autologous osteoprogenitor cells are
      isolated, expanded in vitro, and transplanted to the specific anatomical site
      where the bone is required. Recent studies have gradually elucidated that
      transplanted osteoprogenitor cells are not only a source of bone forming
      osteoblasts, they appear to play multiple roles, such as recruitment of
      endogenous osteoprogenitor cells and immunomodulatory function, at the forefront
      of bone regeneration. This review focuses on the current consensus of cell-based
      bone augmentation therapies with emphasis on cell sources, transplanted cell
      survival, endogenous stem cell recruitment and immunomodulatory function of
      transplanted osteoprogenitor cells. Furthermore, if we were able to control the
      mobilization of endogenous osteoprogenitor cells, large-scale surgery may no
      longer be necessary. Such treatment strategy may open a new era of safer and more
      effective alveolar ridge augmentation treatment options. 

PMID- 25749436
TI  - Reactivity of zirconia with phosphate-bonded investments for hot-pressing.
AB  - PURPOSE: The aim of the present study was to investigate the reactivity of
      zirconia to phosphate-bonded investment on the process of hot-pressing technique.
      METHODS: Disc-shaped specimens, 16 mm diameter and 0.4mm thick were prepared by
      cutting and grinding. These specimens were finally sintered. Half of them were
      sandblasted. The non-sandblasted specimens were used for controls. Both of
      zirconia discs with and without sandblasting were invested into the three kinds
      of phosphate-bonded investment. The investments were fired and broken to take out
      specimens. The biaxial strengths were measured in the way of the biaxial flexural
      tests according to ISO-6872. RESULTS: The biaxial strengths were ranged 762-1200
      MPa at the average. The biaxial strengths of sandblasted zirconia discs heated
      with phosphate-bonded investment were decreased significantly (p < 0.01). SEM and
      EPMA revealed that the various compounds were observed on the sandblasted
      specimens. XRD revealed that surfaces of specimens heated with the phosphate
      bonded investment showed the formation of phosphate compounds. CONCLUSIONS: The
      phosphate compounds inhibit stress-induction phase transformation of zirconia and
      decrease the biaxial strength.

PMID- 25749437
TI  - Factors affecting the selection of minimally invasive surgery for stage 0/I
      colorectal cancer.
AB  - PURPOSE: To evaluate which factors affect selection of minimally invasive surgery
      (MIS) or open procedures for patients with stage 0/I colorectal cancer. The short
      term and oncologic outcomes of MIS were also compared to those of open
      procedures. METHODS: A total of 181 consecutive patients underwent either MIS
      (laparoscopy: n = 146, robot: n = 8) or open (n = 27) colorectal resection for
      stage 0/I disease. RESULTS: Elderly patients (>=80) were more common in the open
      procedure group (22.2%) than the MIS (7.8%) group (p = .02). Surgeon A performed
      more MIS procedures than surgeon B (p = .003). There were no differences in the
      30-day complication rate between open (37%) and MIS (21.4%) groups (p = .08).
      Time to tolerable diet (p = .002) and length of hospital stay (p = .02) were
      shorter in the MIS group. There were no differences in the cancer-specific
      survival (p = .71) and recurrence-free survival rates (p = .67) between open and
      MIS procedures. CONCLUSIONS: Patient factors (old age) and surgeon factors
      (surgeon B) were barriers to the choice of MIS. Old age and operating surgeons
      were not associated with adverse 30-day complications. The short-term and
      oncologic outcomes of MIS were comparable to those of open procedures. It is safe
      to expand the indication for MIS to elderly patients.

PMID- 25749438
TI  - Effect of surgical experience on the macroscopic diagnosis of appendicitis: a
      retrospective cohort study.
AB  - BACKGROUND: We aimed to determine whether intraoperative macroscopic assessment
      of the appendix improves with surgical experience and whether the accuracy of the
      intraoperative assessment of the appendix is different in respect to sex of the
      patient. METHODS: Medical records of all appendicectomies performed during an 18
      month period (2011-2012) at Westmead Hospital, Australia were reviewed. Accuracy
      of intraoperative macroscopic description correlating to histopathology was
      compared between groups based on the training level of the surgeon. RESULTS:
      Correlation between the intraoperative diagnosis and final histopathology result
      was 83.5% of the 303 cases. The diagnostic accuracy amongst junior trainees,
      senior trainees and consultants did not differ with accuracy rates of 85%, 81.6%
      and 88.2% respectively, (P = 0.44). The false negative rate was higher in females
      than in males (19.1% versus 7.2%; P = 0.007). CONCLUSIONS: Our findings
      demonstrated that operator experience does not affect the accuracy of the
      intraoperative assessment of appendixes. We recommend that an appendicectomy be
      performed when clinically indicated regardless of macroscopic appearance.

PMID- 25749439
TI  - Factors Affecting Bacterial Inactivation during High Hydrostatic Pressure
      Processing of Foods: A Review.
AB  - Although, the High Hydrostatic Pressure (HHP) technology has been gaining gradual
      popularity in food industry since last two decades, intensive research is needed
      to explore the missing information. Bacterial inactivation in food by using HHP
      applications can be enhanced by getting deeper insights of the process. Some of
      these aspects have been already studied in detail (like pressure, time, and
      temperature, etc.), while some others still need to be investigated in more
      details (like pH, rates of compression, and decompression, etc.). Selection of
      process parameters is mainly dependent on type of matrix and target bacteria.
      This intensive review provides comprehensive information about the variety of
      aspects that can determine the bacterial inactivation potential of HHP process
      indicating the fields of future research on this subject including pH shifts of
      the pressure treated samples and critical limits of compression and decompression
      rates to accelerate the process efficacy. 

PMID- 25749440
TI  - Skeletal muscle signature of a champion sprint runner.
AB  - We had the unique opportunity to study the skeletal muscle characteristics, at
      the single fiber level, of a world champion sprint runner who is the current
      indoor world record holder in the 60-m hurdles (7.30 s) and former world record
      holder in 110-m hurdles (12.91 s). Muscle biopsies were obtained from the vastus
      lateralis at rest and 4 h after a high-intensity exercise challenge (4 * 7
      repetitions of resistance exercise). Single muscle fiber analyses were conducted
      for fiber type distribution (myosin heavy chain, MHC), fiber size, contractile
      function (strength, speed, and power) and mRNA expression (before and after the
      exercise bout). The world-class sprinter's leg muscle had a high abundance (24%)
      of the pure MHC IIx muscle fibers with a total fast-twitch fiber population of
      71%. Power output of the MHC IIx fibers (35.1 +/- 1.4 W/l) was 2-fold higher than
      MHC IIa fibers (17.1 +/- 0.5 W/l) and 14-fold greater than MHC I fibers (2.5 +/-
      0.1 W/l). Additionally, the MHC IIx fibers were highly responsive to intense
      exercise at the transcriptional level for genes involved with muscle growth and
      remodeling (Fn14 and myostatin). To our knowledge, the abundance of pure MHC IIx
      muscle fibers is the highest observed in an elite sprinter. Further, the power
      output of the MHC IIa and MHC IIx muscle fibers was greater than any human values
      reported to date. These data provide a myocellular basis for the high level of
      sprinting success achieved by this individual. 

PMID- 25749441
TI  - Glucose uptake during contraction in isolated skeletal muscles from neuronal
      nitric oxide synthase MU knockout mice.
AB  - Inhibition of nitric oxide synthase (NOS) significantly attenuates the increase
      in skeletal muscle glucose uptake during contraction/exercise, and a greater
      attenuation is observed in individuals with Type 2 diabetes compared with healthy
      individuals. Therefore, NO appears to play an important role in mediating muscle
      glucose uptake during contraction. In this study, we investigated the involvement
      of neuronal NOSMU (nNOSMU), the main NOS isoform activated during contraction, on
      skeletal muscle glucose uptake during ex vivo contraction. Extensor digitorum
      longus muscles were isolated from nNOSMU(-/-) and nNOSMU(+/+) mice. Muscles were
      contracted ex vivo in a temperature-controlled (30 degrees C) organ bath with or
      without the presence of the NOS inhibitor N(G)-monomethyl-l-arginine (L-NMMA) and
      the NOS substrate L-arginine. Glucose uptake was determined by radioactive
      tracers. Skeletal muscle glucose uptake increased approximately fourfold during
      contraction in muscles from both nNOSMU(-/-) and nNOSMU(+/+) mice. L-NMMA
      significantly attenuated the increase in muscle glucose uptake during contraction
      in both genotypes. This attenuation was reversed by L-arginine, suggesting that L
      NMMA attenuated the increase in muscle glucose uptake during contraction by
      inhibiting NOS and not via a nonspecific effect of the inhibitor. Low levels of
      NOS activity (~4%) were detected in muscles from nNOSMU(-/-) mice, and there was
      no evidence of compensation from other NOS isoform or AMP-activated protein
      kinase which is also involved in mediating muscle glucose uptake during
      contraction. These results indicate that NO regulates skeletal muscle glucose
      uptake during ex vivo contraction independently of nNOSMU.

PMID- 25749442
TI  - Hypoxia-inducible factor-1 modulates the expression of vascular endothelial
      growth factor and endothelial nitric oxide synthase induced by eccentric
      exercise.
AB  - The present study investigated the effects of acute and chronic eccentric
      exercise on the hypoxia-inducible factor (HIF)-1alpha activation response and the
      concomitant modulation of vascular endothelial growth factor (VEGF) and
      endothelial nitric oxide synthase (eNOS) expression in rat skeletal muscle.
      Twenty-four male Wistar rats were randomly assigned to three experimental groups:
      rested control group, acutely exercised group after an intermittent downhill
      protocol for 90 min, and acutely exercise group with a previous eccentric
      training of 8 wk. HIF-1alpha activation, VEGF and eNOS gene expression, protein
      content, and promoter activation were assessed in vastus lateralis muscle
      biopsies. Acute eccentric exercise induced a marked activation of HIF-1alpha and
      resulted in increased VEGF and eNOS mRNA level and protein concentration. The
      binding of HIF-1alpha to the VEGF and eNOS promoters, measured by a chromatin
      immunoprecipitation assay, was undetectable in rested rats, whereas it was
      evident in acutely exercised animals. Acute exercise also increased
      myeloperoxidase, toll-like receptor-4, tumor necrosis factor-alpha, and
      interleukin-1beta protein content, suggesting a contribution of proinflammatory
      stimuli to HIF-1alpha activation and VEGF overexpression. All of these effects
      were partially abolished by training. Moreover, training resulted in an increased
      capillary density. In summary, our findings indicate that eccentric exercise
      prompts an HIF-1alpha response in untrained skeletal muscle that contributes to
      the upregulation of VEGF and eNOS gene expression and is attenuated after an
      eccentric training program. 

PMID- 25749443
TI  - Prior head-down tilt does not impair the cerebrovascular response to head-up
      tilt.
AB  - The hypothesis that cerebrovascular autoregulation was not impaired during head
      up tilt (HUT) that followed brief exposures to varying degrees of prior head-down
      tilt (HDT) was tested in 10 healthy young men and women. Cerebral mean flow
      velocity (MFV) and cardiovascular responses were measured in transitions to a 60
      s period of 75 degrees  HUT that followed supine rest (control) or 15 s HDT at 
      10 degrees , -25 degrees , and -55 degrees . During HDT, heart rate (HR) was
      reduced for -25 degrees  and -55 degrees , and cardiac output was lower at -55
      degrees  HDT. MFV increased during -10 degrees  HDT, but not in the other
      conditions even though blood pressure at the middle cerebral artery (BPMCA)
      increased. On the transition to HUT, HR increased only for -55 degrees 
      condition, but stroke volume and cardiac output transiently increased for -25
      degrees  and -55 degrees . Total peripheral resistance index decreased in
      proportion to the magnitude of HDT and recovered over the first 20 s of HUT. MFV
      was significantly less in all HDT conditions compared with the control in the
      first 5-s period of HUT, but it recovered quickly. An autoregulation correction
      index derived from MFV recovery relative to BPMCA decline revealed a delay in the
      first 5 s for prior HDT compared with control but then a rapid increase to
      briefly exceed control after -55 degrees  HDT. This study showed that
      cerebrovascular autoregulation is modified by but not impaired by brief HDT prior
      to HUT and that cerebral MFV recovered quickly and more rapidly than arterial
      blood pressure to protect against cerebral hypoperfusion and potential syncope. 

PMID- 25749444
TI  - Clinical outcomes and cardiovascular responses to exercise training in heart
      failure patients with preserved ejection fraction: a systematic review and meta
      analysis.
AB  - Exercise training induces physical adaptations for heart failure patients with
      systolic dysfunction, but less is known about those patients with preserved
      ejection fraction. To establish whether exercise training produces changes in
      peak Vo2 and related measures, quality of life, general health, and diastolic
      function in heart failure patients with preserved ejection fraction. We conducted
      a MEDLINE search (1985 to October 10, 2014), for exercise-based rehabilitation
      trials in heart failure, using search terms "exercise training, heart failure
      with preserved ejection fraction, heart failure with normal ejection fraction,
      peak Vo2, and diastolic heart dysfunction". Seven intervention studies were
      included providing a total of 144 exercising subjects and 114 control subjects, a
      total of 258 participants. Peak Vo2 increased by a mean difference (MD) 2.13
      ml.kg(-1).min(-1) [95% confidence interval (CI) 1.54 to 2.71, P < 0.00001] in
      exercise training vs. sedentary control, equating to a 17% improvement from
      baseline. The corresponding data are provided for the following exercise test
      variables: Ve/Vco2 slope, MD 0.85 ml.kg(-1).min(-1) (95% CI 0.05 to 1.65, P =
      0.04); maximum heart rate, MD 5.60 beats per minute (95% CI 3.95 to 7.25, P <
      0.00001); Six-Minute Walk Test, MD 32.1 m (95% CI 17.2 to 47.1, P < 0.0001); and
      indices of diastolic function: E/A ratio, MD 0.07 (95% CI 0.02 to 0.12, P =
      0.005); E/E' ratio MD -2.31 (95% CI -3.44 to -1.19, P < 0.0001); deceleration
      time (DT), MD -13.2 ms (95% CI -19.8 to -6.5, P = 0.0001); and quality of life:
      Minnesota Living with Heart Failure Questionnaire, MD -6.50 (95% CI -9.47 to 
      3.53, P < 0.0001); and short form-36 health survey (physical dimension), MD 15.6
      (95% CI 7.4 to 23.8, P = 0.0002). In 3,744 h patient-hours of training, not one
      death was directly attributable to exercise. Exercise training appears to effect
      several health-related improvements in people with heart failure and preserved
      ejection fraction.

PMID- 25749446
TI  - Cardiac hypertrophy reduction in SHR by specific silencing of myocardial
      Na(+)/H(+) exchanger.
AB  - We examined the effect of specific and local silencing of sodium/hydrogen
      exchanger isoform 1 (NHE1) with a small hairpin RNA delivered by lentivirus (L
      shNHE1) in the cardiac left ventricle (LV) wall of spontaneously hypertensive
      rats, to reduce cardiac hypertrophy. Thirty days after the lentivirus was
      injected, NHE1 protein expression was reduced 53.3 +/- 3% in the LV of the L
      shNHE1 compared with the control group injected with L-shSCR (NHE1 scrambled
      sequence), without affecting its expression in other organs, such as liver and
      lung. Hypertrophic parameters as LV weight-to-body weight and LV weight-to-tibia
      length ratio were significantly reduced in animals injected with L-shNHE1 (2.32
      +/- 0.5 and 19.30 +/- 0.42 mg/mm, respectively) compared with L-shSCR-injected
      rats (2.68 +/- 0.06 and 21.53 +/- 0.64 mg/mm, respectively). Histochemical
      analysis demonstrated a reduction of cardiomyocytes cross-sectional area in
      animals treated with L-shNHE1 compared with L-shSCR (309,81 +/- 20,86 vs. 424,52
      +/- 21 MUm(2), P < 0.05). Echocardiography at the beginning and at the end of the
      treatment showed that shNHE1 expression for 30 days induced 9% reduction of LV
      mass. Also, animals treated with L-shNHE1 exhibited a reduced LV wall thickness
      without changing LV diastolic dimension and arterial pressure, indicating an
      increased parietal stress. In addition, midwall shortening was not modified,
      despite the increased wall tension, suggesting an improvement of cardiac
      function. Chronic shNHE1 expression in the heart emerges as a possible
      methodology to reduce pathological cardiac hypertrophy, avoiding potentially
      undesired effects caused from a body-wide inhibition of NHE1.

PMID- 25749445
TI  - Impaired myocardial function does not explain reduced left ventricular filling
      and stroke volume at rest or during exercise at high altitude.
AB  - Impaired myocardial systolic contraction and diastolic relaxation have been
      suggested as possible mechanisms contributing to the decreased stroke volume (SV)
      observed at high altitude (HA). To determine whether intrinsic myocardial
      performance is a limiting factor in the generation of SV at HA, we assessed left
      ventricular (LV) systolic and diastolic mechanics and volumes in 10 healthy
      participants (aged 32 +/- 7; mean +/- SD) at rest and during exercise at sea
      level (SL; 344 m) and after 10 days at 5,050 m. In contrast to SL, LV end
      diastolic volume was ~19% lower at rest (P = 0.004) and did not increase during
      exercise despite a greater untwisting velocity. Furthermore, resting SV was lower
      at HA (~17%; 60 +/- 10 vs. 70 +/- 8 ml) despite higher LV twist (43%), apical
      rotation (115%), and circumferential strain (17%). With exercise at HA, the
      increase in SV was limited (12 vs. 22 ml at SL), and LV apical rotation failed to
      augment. For the first time, we have demonstrated that EDV does not increase upon
      exercise at high altitude despite enhanced in vivo diastolic relaxation. The
      increase in LV mechanics at rest may represent a mechanism by which SV is
      defended in the presence of a reduced EDV. However, likely because of the higher
      LV mechanics at rest, no further increase was observed up to 50% peak power.
      Consequently, although hypoxia does not suppress systolic function per se, the
      capacity to increase SV through greater deformation during submaximal exercise at
      HA is restricted.

PMID- 25749447
TI  - Mechanisms contributing to the response of upper-airway muscles to changes in
      airway pressure.
AB  - This study assessed the effects of inhaled lignocaine to reduce upper airway
      surface mechanoreceptor activity on 1) basal genioglossus and tensor palatini
      EMG, 2) genioglossus reflex responses to large pulses (~10 cmH2O) of negative
      airway pressure, and 3) upper airway collapsibility in 15 awake individuals.
      Genioglossus and tensor palatini muscle EMG and airway pressures were recorded
      during quiet nasal breathing and during brief pulses (250 ms) of negative upper
      airway pressure. Lignocaine reduced peak inspiratory (5.6 +/- 1.5 vs. 3.8 +/-
      1.1% maximum; mean +/- SE, P < 0.01) and tonic (2.8 +/- 0.8 vs. 2.1 +/- 0.7%
      maximum; P < 0.05) genioglossus EMG during quiet breathing but had no effect on
      tensor palatini EMG (5.0 +/- 0.8 vs. 5.0 +/- 0.5% maximum; P = 0.97).
      Genioglossus reflex excitation to negative pressure pulses decreased after
      anesthesia (60.9 +/- 20.7 vs. 23.6 +/- 5.2 MUV; P < 0.05), but not when expressed
      as a percentage of the immediate prestimulus baseline. Reflex excitation was
      closely related to the change in baseline EMG following lignocaine (r(2) = 0.98).
      A short-latency genioglossus reflex to rapid increases from negative to
      atmospheric pressure was also observed. The upper airway collapsibility index
      (%difference) between nadir choanal and epiglottic pressure increased after
      lignocaine (17.8 +/- 3.7 vs. 28.8 +/- 7.5%; P < 0.05). These findings indicate
      that surface receptors modulate genioglossus but not tensor palatini activity
      during quiet breathing. However, removal of input from surface mechanoreceptors
      has minimal effect on genioglossus reflex responses to large (~10 cmH2O), sudden
      changes in airway pressure. Changes in pressure rather than negative pressure per
      se can elicit genioglossus reflex responses. These findings challenge previous
      views and have important implications for upper airway muscle control. 

PMID- 25749448
TI  - Exercise training-induced bradycardia: evidence for enhanced parasympathetic
      regulation without changes in intrinsic sinoatrial node function.
AB  - The mechanisms responsible for exercise-induced reductions in baseline heart rate
      (HR), known as training bradycardia, remain controversial. Therefore, changes in
      cardiac autonomic regulation and intrinsic sinoatrial nodal (SAN) rate were
      evaluated using dogs randomly assigned to either a 10- to 12-wk exercise training
      (Ex, n = 15) or an equivalent sedentary period (Sed, n = 10). Intrinsic HR was
      revealed by combined autonomic nervous system (ANS) blockade (propranolol +
      atropine, iv) before and after completion of the study. At the end of the study,
      SAN function was further evaluated by examining the SAN recovery time (SNRT)
      following rapid atrial pacing and the response to adenosine in anesthetized
      animals. As expected, both the response to submaximal exercise and baseline HR
      significantly (P < 0.01) decreased, and heart rate variability (HRV; e.g., high
      frequency R-R interval variability) significantly (P < 0.01) increased in the Ex
      group but did not change in the Sed group. Atropine also induced significantly (P
      < 0.01) greater reductions in HRV in the Ex group compared with the Sed group;
      propranolol elicited similar HR and HRV changes in both groups. In contrast,
      neither intrinsic HR (Ex before, 141.2 +/- 6.7; Ex after, 146.0 +/- 8.0 vs. Sed
      before, 143.3 +/- 11.1; Sed after, 141.0 +/- 11.3 beats per minute), the response
      to adenosine, corrected SNRT, nor atrial fibrosis and atrial fibrillation
      inducibility differed in the Ex group vs. the Sed group. These data suggest that
      in a large-animal model, training bradycardia results from an enhanced cardiac
      parasympathetic regulation and not from changes in intrinsic properties of the
      SAN. 

PMID- 25749449
TI  - Hemoglobin mass and intravascular volume kinetics during and after exposure to
      3,454-m altitude.
AB  - High altitude (HA) exposure facilitates a rapid contraction of plasma volume (PV)
      and a slower occurring expansion of hemoglobin mass (Hbmass). The kinetics of the
      Hbmass expansion has never been examined by multiple repeated measurements, and
      this was our primary study aim. The second aim was to investigate the mechanisms
      mediating the PV contraction. Nine healthy, normally trained sea-level (SL)
      residents (8 males, 1 female) sojourned for 28 days at 3,454 m. Hbmass was
      measured and PV was estimated by carbon monoxide rebreathing at SL, on every 4th
      day at HA, and 1 and 2 wk upon return to SL. Four weeks at HA increased Hbmass by
      5.26% (range 2.5-11.1%; P < 0.001). The individual Hbmass increases commenced
      with up to 12 days of delay and reached a maximal rate of 4.04 +/- 1.02 g/day
      after 14.9 +/- 5.2 days. The probability for Hbmass to plateau increased steeply
      after 20-24 days. Upon return to SL Hbmass decayed by -2.46 +/- 2.3 g/day,
      reaching values similar to baseline after 2 wk. PV, aldosterone concentration,
      and renin activity were reduced at HA (P < 0.001) while the total circulating
      protein mass remained unaffected. In summary, the Hbmass response to HA exposure
      followed a sigmoidal pattern with a delayed onset and a plateau after ~3 wk. The
      decay rate of Hbmass upon descent to SL did not indicate major changes in the
      rate of erythrolysis. Moreover, our data support that PV contraction at HA is
      regulated by the renin-angiotensin-aldosterone axis and not by changes in oncotic
      pressure.

PMID- 25749451
TI  - Structural biology: Hand in hand structure and function of T6SSs.

PMID- 25749452
TI  - A switch in time.

PMID- 25749450
TI  - Salmonellae interactions with host processes.
AB  - Salmonellae invasion and intracellular replication within host cells result in a
      range of diseases, including gastroenteritis, bacteraemia, enteric fever and
      focal infections. In recent years, considerable progress has been made in our
      understanding of the molecular mechanisms that salmonellae use to alter host cell
      physiology; through the delivery of effector proteins with specific activities
      and through the modulation of defence and stress response pathways. In this
      Review, we summarize our current knowledge of the complex interplay between
      bacterial and host factors that leads to inflammation, disease and, in most
      cases, control of the infection by its animal hosts, with a particular focus on
      Salmonella enterica subsp. enterica serovar Typhimurium. We also highlight gaps
      in our knowledge of the contributions of salmonellae and the host to disease
      pathogenesis, and we suggest future avenues for further study. 

PMID- 25749453
TI  - Bacterial genetics: What CRISPR memories are made of.

PMID- 25749456
TI  - 7th WINFOCUS Italian Congress on Ultrasound in Emergency, Anaesthesiology and
      Critical Care.

PMID- 25749454
TI  - Now you see me, now you don't: the interaction of Salmonella with innate immune
      receptors.
AB  - Salmonella enterica serovars are associated with an estimated 1 million deaths
      annually and are also useful model organisms for investigating the mechanisms of
      host-bacterium interactions. The insights gained from studies on non-typhoidal
      Salmonella (NTS) serovars have provided a fascinating overview of the mechanisms
      by which the innate immune system detects and responds to bacterial pathogens.
      However, specific virulence factors and changes in virulence gene regulation in
      S. enterica subsp. enterica serovar Typhi alter the innate immune responses to
      this pathogen. In this Review, we compare and contrast the interactions of S.
      Typhi and NTS serovars with host innate immune receptors and discuss why the
      disease manifestations associated with S. Typhi infection differ considerably
      from those associated with the closely related NTS serovars. 

PMID- 25749455
TI  - Innovations in EMS Fellow Education.

PMID- 25749457
TI  - Hematologic and immunological characteristics of Henoch-Schonlein purpura in rat
      and rabbit models induced with ovalbumin based on type III hypersensitivity.
AB  - Henoch-Schonlein purpura (HSP) is a common systemic vasculitis in children.
      Animal models of HSP are needed to better understand the mechanism of HSP. Here,
      we investigated hematologic and immunologic profiles in HSP rat and rabbit
      models. Models were established with ovalbumin (OVA) based on type III
      hypersensitivity. During the acute phase, the models exhibited varying degrees of
      cutaneous purpura, joint inflammatory response, gastrointestinal bleeding,
      glomerular capsule protein exudation, vascular dilatation, and increased IgA
      expression and immune complex deposition. Twenty four hours after antigen
      challenge, compared with the controls, the models showed a significantly
      increased white blood cell count and granulocytes count and percentage, decreased
      number and percentage of lymphocytes, no change in platelet concentration,
      significantly increased serum IL-4 and TNF-alpha levels, and decreased CD4(+) T
      cell, CD4/CD8 ratio, and C3 and C4 levels. Compared with the hematologic and
      immunologic profiles in pediatric HSP patients, the rat and rabbit HSP models can
      mimic pediatric HSP characteristics. Our studies provide two useful animal models
      for further investigations of the pathogenesis, diagnosis, drug screening and
      treatment of HSP. 

PMID- 25749458
TI  - Blood-brain barrier dysfunction following traumatic brain injury: correlation of
      K(trans) (DCE-MRI) and SUVR (99mTc-DTPA SPECT) but not serum S100B.
AB  - OBJECTIVE: Damage to the blood-brain barrier (BBB) is an important secondary
      mechanism that occurs following traumatic brain injury (TBI) and may provide a
      potential therapeutic target to improve patient outcome. For such a progress to
      be realised, an accurate assessment of BBB compromise needs to be established.
      METHODS: Fourteen patients with TBI were prospectively recruited. Post-traumatic
      BBB dysfunction was assessed using dynamic contrast-enhanced MRI (DCE-MRI),
      single-photon emission computerised tomography (SPECT) and serum S100B levels.
      RESULTS: A statistically significant correlation between standardised uptake
      value ratio (SUVR) calculated from 99mTc-DTPA SPECT and K(trans) (a volume
      transfer constant) from DCE-MRI was found for those eight patients who had
      concurrent scans. The positive correlation persisted when the data were corrected
      for patient age, number of days following trauma and both parameters combined. We
      found no statistically significant correlation between either of the imaging
      modalities and concurrent serum S100B levels. DISCUSSION: The correlation of
      SPECT with DCE-MRI suggests that either scan may be used to assess post-traumatic
      BBB damage. We could not support serum S100B to be an accurate measure of BBB
      damage when sampled a number of days following injury but the small number of
      patients, the heterogeneity in TBI patients and the delay following injury makes
      any firm conclusions regarding S100B and BBB difficult.

PMID- 25749459
TI  - Umbilical laparoendoscopic partial cystectomy.
AB  - OBJECTIVE: To present our center's experience in single-port umbilical
      laparoendoscopic partial cystectomies, in both benign and malignant pathologies.
      Patient characteristics, perioperative aspects and the surgical techniques used
      are reviewed. MATERIAL AND METHOD: Since May 2012, five patients have undergone a
      transumbilical single-port laparoendoscopic partial cystectomy with curved
      equipment through a reusable multichannel system and a 3.5mm accessory trocar.
      Patients were three males and two females aged between 28 and 78 (median: 44+/
      42.5) years. The etiologies were endometriosis (in 2 cases), a tumor in the
      diverticulum, a congenital bladder diverticulum and ureterocele (1 case of each).
      RESULTS: Median surgery time was 273+/-163.4minutes, and intraoperative bleeding
      250+/-175ml. None of the patients required transfusion. The postoperative period
      was uneventful, with good results and no complications. The hospital stay was 3+/
      1 days. With monitoring of 20+/-17.5 months, morphological and functional
      recovery in the bladder and ureter was confirmed in all cases and the patient
      with neoplastic disease was disease-free more than 2 years after the surgery.
      CONCLUSIONS: An umbilical laparoendoscopic partial cystectomy represents a viable
      surgical option and ensures that excellent surgical and cosmetic results are
      achieved.

PMID- 25749460
TI  - Uncontrolled non-heartbeating donors (types i-ii) with normothermic recirculation
      vs. heartbeating donors: evaluation of functional results and survival.
AB  - OBJECTIVE: Non-heartbeating donors (NHBD) are an alternative to heartbeating
      donors (HBD). Our objective was to compare functional results and kidney survival
      from NHBDs and HBDs. MATERIAL AND METHODS: A retrospective study comparing the
      results of 236 normothermically preserved kidneys from type i and ii type NHBDs
      with the results of 250 from HBDs that were transplanted in our center between
      2005 and 2012. Homogeneity between groups was tested and we evaluated the
      presence of delayed graft function (DGF) associated with pretransplant variables
      of the donor and recipient. RESULTS: Both groups show homogeneity in
      pretransplant characteristics in terms of: age, HLA incompatibilities, and
      recipient hemodialysis time. Average follow-up time was 33 months (range 0-87)
      for NHBDs and 38 months (range 0-90) for HBDs. 5.5% of NHBDs showed primary non
      function (PNF) vs. 4% of HBDs (P=.42) and 80.9% of DGF vs. 46.8% of HBDs
      (P<.001). At the end of the follow-up, there were no statistically significant
      differences in the survival of grafts (92.8% for NHBD vs. 93.6% for HBD, P=.71)
      and recipients (99.1% NHBD vs. 98.6% HBD, P=.28). CONCLUSIONS: Although the DGF
      percentage was greater for NHBDs, final creatinine as well as graft and recipient
      survival were similar for both groups. Therefore, in our experience, kidneys from
      NHBDs have similar results to those from HBDs and are an excellent source of
      organs for transplantation.

PMID- 25749461
TI  - Defining multidrug-resistant tuberculosis: correlating GenoType MTBDRplus assay
      results with minimum inhibitory concentrations.
AB  - This study correlates MICs of rifampicin (RIF) and isoniazid (INH) with GenoType
      MTBDRplus assay results for drug-resistant Mycobacterium tuberculosis (MTB)
      clinical isolates. MICs of RIF and INH were established for 84 and 90 isolates,
      respectively, testing 7 concentrations of each drug. Genotypic resistance to each
      drug was determined by GenoType MTBDRplus assay with 50 representative mutations
      confirmed by pyrosequencing, with mutations in the rpoB gene associated with RIF
      resistance and mutations in the katG and/or inhA genes associated with INH
      resistance. Based upon the correlation of MICs with specific genetic profiles,
      relative resistance levels were established for each isolate. Results indicate
      that MTB phenotypic resistance, currently based upon the testing of isolate
      susceptibility to a single drug concentration, may be more accurately profiled
      via quantitative MICs, and therefore, the correlation of molecular diagnostic
      results with specific MICs may allow for more optimal treatment of infections. 

PMID- 25749462
TI  - Utility of recombinant fragment C for assessment of anti-tetanus antibodies in
      plasma.
AB  - Anti-tetanus antibodies in biological samples are typically detected using an
      enzyme-linked immunosorbent assay based on toxoided tetanus neurotoxin as
      antigen. We demonstrate that recombinantly produced fragment C of the toxin heavy
      chain is an effective alternative antigen for assessment of tetanus-immune status
      in plasma samples. 

PMID- 25749463
TI  - Unusual Tract and Complication of a Percutaneous Gastrostomy Tube.

PMID- 25749464
TI  - Acute Pancreatitis in the Pediatric Intensive Care Unit.
AB  - AIM: The aim of this study is to describe the demographics and outcomes of
      children with a discharge diagnosis of acute pancreatitis (AP) from the pediatric
      intensive care unit (PICU). METHODS: Data for this retrospective cohort study
      were obtained from a multisite, clinical PICU database. PICU discharges with a
      primary or secondary diagnosis of AP (SAP) between 2009 and 2013 from 113 centers
      were reviewed. We also obtained the Pediatric Index of Mortality 2 Risk of
      Mortality (PIM2ROM), an indicator of the severity of illness. RESULTS: Of 360,162
      PICU discharges, 2026 with a diagnosis of AP were analyzed further (0.56%)-331
      had a primary diagnosis of AP, whereas 1695 had a SAP. Among children with
      primary AP, median PIM2ROM was 1.0% (interquartile range [IQR] 0.8%-1.4%). Fifty
      five children with primary AP (16.6%) required mechanical ventilation (MV) for a
      median of 3.8 days (IQR 1.0-9.3). The length of stay (LOS) in PICU was a median
      of 2.95 days (IQR 1.53-5.90). Only 1 patient died (mortality 0.3%). Among
      children with secondary AP, median PIM2ROM was 1.1% (IQR 0.8%-4.0%). A total of
      711 children (42.0%) with secondary AP required MV for a median of 5.8 days (IQR
      1.8-14.0). PICU LOS was a median of 4.43 days (IQR 1.84-11.22). There were 115
      deaths in this group (mortality 6.8%). Median PIM2ROM, PICU LOS, mortality (all P
      < 0.001), and length of MV (P = 0.035) were significantly greater in children
      with secondary AP than with primary AP. CONCLUSIONS: Unlike in adult series,
      children with AP rarely die. Patients with secondary AP experience more morbidity
      and mortality than patients with primary AP.

PMID- 25749465
TI  - Source apportionment of airborne nanoparticles in a Middle Eastern city using
      positive matrix factorization.
AB  - Airborne nanoparticles have been studied worldwide, but little is known about
      their sources in the Middle East region, where hot, arid and dusty climatic
      conditions generally prevail. For the first time in Kuwait, we carried out size
      resolved measurements of particle number distributions (PNDs) and concentrations
      (PNCs) in the 5-1000 nm size range. Measurements were made continuously for 31
      days during the summer months of May and June 2013 using a fast-response
      differential mobility spectrometer (Cambustion DMS500) at a sampling rate of 10
      Hz. Sources and their contributions were identified using the positive matrix
      factorization (PMF) approach that was applied to the PND data. Simultaneous
      measurements of gaseous pollutants (i.e., O3, NO, NOx, SO2 and CO), PM10, wind
      speed and direction were also carried out to aid the interpretation of the PMF
      results through the conditional probability function plots and Pearson product
      moment correlations. Six major sources of PNCs were identified, contributing ~46%
      (fresh traffic emissions), 27% (aged traffic emissions), 9% (industrial
      emissions), 9% (regional background), 6% (miscellaneous sources) and 3% (Arabian
      dust transport) of the total PNCs. The sources of nanoparticles and their PND
      profiles identified could serve as reference data to design more detailed field
      studies in the future and treat these sources in dispersion modelling and health
      impact assessment studies. 

PMID- 25749466
TI  - Long-term Clinical Outcomes Following Resectoscopic Endometrial Ablation of Non
      atypical Endometrial Hyperplasia in Women With Abnormal Uterine Bleeding.

PMID- 25749467
TI  - Long-term Clinical Outcomes After Resectoscopic Endometrial Ablation of
      Nonatypical Endometrial Hyperplasia in Women With Abnormal Uterine Bleeding.

PMID- 25749468
TI  - Adipokine levels during the first or early second trimester of pregnancy and
      subsequent risk of gestational diabetes mellitus: A systematic review.
AB  - OBJECTIVE: We aimed to systematically review available literature linking
      adipokines to gestational diabetes mellitus (GDM) for a comprehensive
      understanding of the roles of adipokines in the development of GDM. METHODS: We
      searched PubMed/MEDLINE and EMBASE databases for published studies on adipokines
      and GDM through October 21, 2014. We included articles if they had a prospective
      study design (i.e., blood samples for adipokines measurement were collected
      before GDM diagnosis). Random-effects models were used to pool the weighted mean
      differences comparing levels of adipokines between GDM cases and non-GDM
      controls. RESULTS: Of 1523 potentially relevant articles, we included 25
      prospective studies relating adipokines to incident GDM. Our meta-analysis of
      nine prospective studies on adiponectin and eight prospective studies on leptin
      indicated that adiponectin levels in the first or early second trimester of
      pregnancy were 2.25 MUg/ml lower (95% CI: 1.75-2.75), whereas leptin levels were
      7.25 ng/ml higher (95% CI 3.27-11.22), among women who later developed GDM than
      women who did not. Prospective data were sparse and findings were inconsistent
      for visfatin, retinol binding protein (RBP-4), resistin, tumor necrosis factor
      alpha (TNF-alpha), interleukin-6 (IL-6), and vaspin. We did not identify
      prospective studies for several novel adipokines, including chemerin, apelin,
      omentin, or adipocyte fatty acid-binding protein. Moreover, no published
      prospective studies with longitudinal assessment of adipokines and incident GDM
      were identified. CONCLUSION: Adiponectin levels in the first or second trimester
      of pregnancy are lower among pregnant women who later develop GDM than non-GDM
      women, whereas leptin levels are higher. Well-designed prospective studies with
      longitudinal assessment of adipokines during pregnancy are needed to understand
      the trajectories and dynamic associations of adipokines with GDM risk.

PMID- 25749469
TI  - Biochemical properties and structure analysis of a DAG-Like lipase from
      Malassezia globosa.
AB  - Diacylglycerol (DAG)-like lipases are found to play an important role in the life
      sciences and industrial fields. A putative DAG-like lipase (MgMDL2) from
      Malassezia globosa was cloned and expressed in recombinant Pichia pastoris. The
      recombinant MgMDL2 was expressed as a glycosylated protein and purified into
      homogeneity by anion exchange chromatography. The activity of recombinant MgMDL2
      was optimal at 15  degrees C and pH 6.0, and it keeps over 50% of relative
      activity at 5  degrees C, suggesting that MgMDL2 was a cold active lipase. MgMDL2
      retained over 80% of initial activity after incubation at 30 and 40  degrees C
      for 2.5 h, but it was not stable at 50  degrees C. Incubation of methanol and
      ethanol at a concentration of 30% for 2 h did not affect the recombinant enzyme
      activity, while metal ions, including Ca2+, Mn2+ and Ni2+, sharply inhibited the
      MgMDL2 activity at 5 mM by 42%, 35% and 36%, respectively. MgMDL2 exhibited a
      preference for medium chain-length esters with highest activity toward p
      nitrophenyl caprylate, while it was active on mono- and diacylglycerol but not on
      triacylglycerol, indicating that it was a typical DAG-like lipase. By homology
      modeling, Phe278 was predicted to be involved in the preference of MgMDL2 for
      monoacyl- and diacyl-glyceride substrates, but not triglycerides. 

PMID- 25749470
TI  - Silk fibroin-based nanoparticles for drug delivery.
AB  - Silk fibroin (SF) is a protein-based biomacromolecule with excellent
      biocompatibility, biodegradability and low immunogenicity. The development of SF
      based nanoparticles for drug delivery have received considerable attention due to
      high binding capacity for various drugs, controlled drug release properties and
      mild preparation conditions. By adjusting the particle size, the chemical
      structure and properties, the modified or recombinant SF-based nanoparticles can
      be designed to improve the therapeutic efficiency of drugs encapsulated into
      these nanoparticles. Therefore, they can be used to deliver small molecule drugs
      (e.g., anti-cancer drugs), protein and growth factor drugs, gene drugs, etc. This
      paper reviews recent progress on SF-based nanoparticles, including chemical
      structure, properties, and preparation methods. In addition, the applications of
      SF-based nanoparticles as carriers for therapeutic drugs are also reviewed. 

PMID- 25749471
TI  - Secretion of human protein C in mouse milk.
AB  - To determine the production of recombinant human protein C (rec-hPC) in milk, we
      created two homozygous mice lines for the goat beta-casein/hPC transgene. Females
      and males of both lines (#10 and #11) displayed normal growth, fertility, and
      lactated normally. The copy number of the transgene was about fivefold higher in
      #10 line as compared to #11 line. mRNA expression of the transgene was only
      detected in the mammary glands of both lines. Furthermore, mRNA expression was
      fourfold higher on day 7 than on day 1 during lactation. Northern blot analysis
      of mRNA expression in the #10 line of transgenic (Tg) mice indicated a strong
      expression of the transgene in the mammary glands after seven days of lactation.
      Comparison of rec-hPC protein level with that of mRNA in the mammary glands
      showed a very similar pattern. A 52-kDa band corresponding to the hPC protein was
      strongly detected in mammary glands of the #10 line during lactation. We also
      detected two bands of heavy chain and one weak band of light chain in the milk of
      the #10 and #11 lines. One single band at 52 kDa was detected from CHO cells
      transfected with hPC cDNA. hPC was mainly localized in the alveolar epithelial
      cell of the mammary glands. The protein is strongly expressed in the cytoplasm of
      the cultured mammary gland tissue. hPC protein produced in milk ranged from 2 to
      28 ng/mL. These experiments indicated that rec-hPC can be produced at high levels
      in mice mammary glands. 

PMID- 25749473
TI  - Monitoring the spatiotemporal activities of miRNAs in small animal models using
      molecular imaging modalities.
AB  - MicroRNAs (miRNAs) are a class of small non-coding RNAs that regulate gene
      expression by binding mRNA targets via sequence complementary inducing
      translational repression and/or mRNA degradation. A current challenge in the
      field of miRNA biology is to understand the functionality of miRNAs under
      physiopathological conditions. Recent evidence indicates that miRNA expression is
      more complex than simple regulation at the transcriptional level. MiRNAs undergo
      complex post-transcriptional regulations such miRNA processing, editing,
      accumulation and re-cycling within P-bodies. They are dynamically regulated and
      have a well-orchestrated spatiotemporal localization pattern. Real-time and
      spatio-temporal analyses of miRNA expression are difficult to evaluate and often
      underestimated. Therefore, important information connecting miRNA expression and
      function can be lost. Conventional miRNA profiling methods such as Northern blot,
      real-time PCR, microarray, in situ hybridization and deep sequencing continue to
      contribute to our knowledge of miRNA biology. However, these methods can seldom
      shed light on the spatiotemporal organization and function of miRNAs in real
      time. Non-invasive molecular imaging methods have the potential to address these
      issues and are thus attracting increasing attention. This paper reviews the state
      of-the-art of methods used to detect miRNAs and discusses their contribution in
      the emerging field of miRNA biology and therapy. 

PMID- 25749472
TI  - Cancer stratification by molecular imaging.
AB  - The lack of specificity of traditional cytotoxic drugs has triggered the
      development of anticancer agents that selectively address specific molecular
      targets. An intrinsic property of these specialized drugs is their limited
      applicability for specific patient subgroups. Consequently, the generation of
      information about tumor characteristics is the key to exploit the potential of
      these drugs. Currently, cancer stratification relies on three approaches: Gene
      expression analysis and cancer proteomics, immunohistochemistry and molecular
      imaging. In order to enable the precise localization of functionally expressed
      targets, molecular imaging combines highly selective biomarkers and intense
      signal sources. Thus, cancer stratification and localization are performed
      simultaneously. Many cancer types are characterized by altered receptor
      expression, such as somatostatin receptors, folate receptors or Her2 (human
      epidermal growth factor receptor 2). Similar correlations are also known for a
      multitude of transporters, such as glucose transporters, amino acid transporters
      or hNIS (human sodium iodide symporter), as well as cell specific proteins, such
      as the prostate specific membrane antigen, integrins, and CD20. This review
      provides a comprehensive description of the methods, targets and agents used in
      molecular imaging, to outline their application for cancer stratification.
      Emphasis is placed on radiotracers which are used to identify altered expression
      patterns of cancer associated markers. 

PMID- 25749474
TI  - Glibenclamide for the treatment of ischemic and hemorrhagic stroke.
AB  - Ischemic and hemorrhagic strokes are associated with severe functional disability
      and high mortality. Except for recombinant tissue plasminogen activator,
      therapies targeting the underlying pathophysiology of central nervous system
      (CNS) ischemia and hemorrhage are strikingly lacking. Sur1-regulated channels
      play essential roles in necrotic cell death and cerebral edema following ischemic
      insults, and in neuroinflammation after hemorrhagic injuries. Inhibiting
      endothelial, neuronal, astrocytic and oligodendroglial sulfonylurea receptor 1
      transient receptor potential melastatin 4 (Sur1-Trpm4) channels and, in some
      cases, microglial KATP (Sur1-Kir6.2) channels, with glibenclamide is protective
      in a variety of contexts. Robust preclinical studies have shown that
      glibenclamide and other sulfonylurea agents reduce infarct volumes, edema and
      hemorrhagic conversion, and improve outcomes in rodent models of ischemic stroke.
      Retrospective studies suggest that diabetic patients on sulfonylurea drugs at
      stroke presentation fare better if they continue on drug. Additional laboratory
      investigations have implicated Sur1 in the pathophysiology of hemorrhagic CNS
      insults. In clinically relevant models of subarachnoid hemorrhage, glibenclamide
      reduces adverse neuroinflammatory and behavioral outcomes. Here, we provide an
      overview of the preclinical studies of glibenclamide therapy for CNS ischemia and
      hemorrhage, discuss the available data from clinical investigations, and conclude
      with promising preclinical results that suggest glibenclamide may be an effective
      therapeutic option for ischemic and hemorrhagic stroke. 

PMID- 25749475
TI  - Faldaprevir for the treatment of hepatitis C.
AB  - The current treatments for chronic hepatitis C virus (HCV) genotype 1 infection
      are combinations of direct-acting antivirals, and faldaprevir is one of the new
      generation of HCV NS3/4A protease inhibitors. At the end of 2013, the US Food and
      Drug Administration (FDA) approved the HCV NS3/4A protease inhibitor simeprevir
      and the HCV NS5B polymerase inhibitor sofosbuvir. Simeprevir or sofosbuvir in
      combination with pegylated interferon and ribavirin are available for clinical
      use. Faldaprevir, another HCV NS3/4A protease inhibitor that also has fewer
      adverse events than telaprevir or boceprevir, is under development. Of interest,
      faldaprevir in combination with pegylated interferon and ribavirin, and
      interferon-free treatment with faldaprevir in combination with deleobuvir plus
      ribavirin provides high sustained virological response rates for HCV genotype 1
      infection. The aim of this article is to review these data concerning
      faldaprevir. Faldaprevir in combination with pegylated interferon and ribavirin
      treatment appears to be associated with fewer adverse events than telaprevir or
      boceprevir in combination with pegylated interferon and ribavirin, and may be one
      of the therapeutic options for treatment-naive patients with HCV genotype 1. The
      interferon-free combination of faldaprevir and deleobuvir with ribavirin was
      effective for HCV genotype 1 infection and may hold promise for interferon
      ineligible and interferon-intolerant patients. 

PMID- 25749476
TI  - Transcriptome microRNA profiling of bovine mammary glands infected with
      Staphylococcus aureus.
AB  - MicroRNAs are small non-coding RNA molecules that are important regulators of
      gene expression at the post-transcriptional level. miRNAs impact the processes of
      cell proliferation, differentiation and apoptosis. Thus, the regulation of miRNA
      expression profiles associated with mastitis will be conducive for its control.
      In this study, Staphylococcus aureus (S. aureus) was administered to the mammary
      gland of Chinese Holstein cows to construct a bacteria-type mastitis model. Total
      RNA was isolated from bovine mammary gland tissue samples from the S. aureus
      induced mastitis group and controls. miRNAs were analyzed using Solexa sequencing
      and bioinformatics processing for the experimental group and control group. Two
      miRNA libraries were constructed respectively. A total of 370 known bovine miRNAs
      and 341 novel mi RNAs were detected for the S. aureus and 358 known bovine miRNAs
      and 232 novel miRNAs for control groups. A total of 77 miRNAs in the S. aureus
      group showed significant differences compared to the control group. GO (Gene
      Ontology) analysis showed these target genes were involved in the regulation of
      cells, binding, etc., while KEGG (Kyoto Encyclopedia of Genes and Genomes)
      analysis showed that these genes were enriched in endocytosis, and olfactory
      transduction pathways involved in cancer. These results provide an experimental
      basis to reveal the cause and regulatory mechanism of mastitis and also suggest
      the potential of miRNAs to serve as biomarkers for the diagnosis of mastitis in
      dairy cows. 

PMID- 25749478
TI  - Nonsuicidal self-injury as a prospective predictor of suicide attempts in a
      clinical sample of military personnel.
AB  - BACKGROUND: Nonsuicidal self-injury (NSSI) is a risk factor for suicide attempts,
      but it has received little attention in military populations, for whom suicide
      rates have doubled over the past decade. In the current study, the relationship
      of NSSI with future suicide attempts was prospectively examined in a sample of
      active duty Soldiers receiving outpatient psychiatric treatment for suicide
      ideation and/or a recent suicide attempt. METHODS: Data were collected as part of
      a two-year prospective study of 152 active duty Soldiers (87% male, 71%
      Caucasian, mean age=27.53) in outpatient mental health care who reported current
      suicide ideation and/or a suicide attempt during the month preceding intake.
      Suicide attempts and NSSI were assessed using the Suicide Attempt Self Injury
      Interview. RESULTS: Forty percent of Soldiers with a history of nonsuicidal self
      injury and 25% of Soldiers with a history of suicide attempt made a suicide
      attempt during the 2-year follow-up. Soldiers with a history of nonsuicidal self
      injury were more than twice as likely to make a subsequent suicide attempt
      (hazard ratio [HR]=2.25, P=.045). Soldiers with a history of suicide attempt were
      no more likely to make a subsequent suicide attempt than Soldiers without a
      previous suicide attempt (HR=.88, P=.787). Thirty percent of Soldiers with a
      history of suicide attempt had also engaged in nonsuicidal self-injury. Forty-two
      percent of Soldiers with histories of both nonsuicidal self-injury and suicide
      attempt made a subsequent suicide attempt and were more likely to make a suicide
      attempt during follow-up than Soldiers with a history of suicide attempt only.
      Number of NSSI episodes, but not number of suicide attempts, was significantly
      associated with increased risk for future suicide attempt. Results were unchanged
      when adjusting for baseline symptom severity. LIMITATIONS: Predominantly male,
      active duty Army sample. CONCLUSIONS: Among Soldiers in outpatient mental health
      care, a history of NSSI is a stronger predictor of future suicide attempts than a
      history of suicide attempts. Soldiers with a history of both NSSI and suicide
      attempt are at especially increased risk.

PMID- 25749477
TI  - Anticarcinogenic properties of medium chain fatty acids on human colorectal, skin
      and breast cancer cells in vitro.
AB  - Colorectal cancer, breast cancer and skin cancer are commonly-reported cancer
      types in the U.S. Although radiation and chemotherapy are routinely used to treat
      cancer, they produce side effects in patients. Additionally, resistance to
      chemotherapeutic drugs has been noticed in cancers. Thus, there is a need for
      effective and safe bioprophylactics and biotherapeutics in cancer therapy. The
      medicinal value of goat milk has been recognized for centuries and is primarily
      attributed to three fatty acids, namely capric, caprylic and caproic acids. This
      research investigates the anticancer property of these fatty acids on human
      colorectal, skin and mammary gland cancer cells. The cancer cells were treated
      with various concentrations of fatty acids for 48 h, and cell viability was
      monitored by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide
      (MTT) reduction assay. Additionally, real-time quantitative PCR (RT-qPCR) was
      performed to elucidate the potential anti-cancer mechanisms of the three fatty
      acids under investigation. Capric, caprylic and caproic acids reduced cancer cell
      viability by 70% to 90% (p < 0.05) compared to controls. RT-qPCR data indicated
      that these natural molecules produced anticancer effects by down-regulating cell
      cycle regulatory genes and up-regulating genes involved in apoptosis. Future
      research will validate the anticancer effect of these fatty acids in an
      appropriate in vivo model. 

PMID- 25749479
TI  - Prevalence and correlates of psychiatric disorders among former juvenile
      detainees in the United States.
AB  - OBJECTIVE: Juvenile offenders face increased liability for psychiatric disorders
      and greater psychopathology, but little is known about the psychiatric status of
      former juvenile delinquents as adults. METHOD: Drawing on data from Wave 1 and
      Wave 2 of the NESARC, logistic regression models examine correlates of
      psychiatric disorders in a large nationally representative sample of former
      juvenile detainees in adulthood (n=1177) compared to adults who did not have a
      history of juvenile offending (n=33,193). Further, we explored the psychosocial
      correlates associated with the increased likelihood of psychiatric disorders
      among former juvenile detainees. RESULTS: Nearly half of former juvenile
      detainees met criteria for one or more psychiatric disorders in the past twelve
      months and approximately two-thirds meet criteria for any lifetime personality
      disorder. Compared to the general population, former juvenile detainees not only
      denote greater psychiatric comorbidity across a range of affective, personality,
      and substance use disorders but are also more likely to report childhood
      adversity. CONCLUSIONS: Former juvenile detainees experience significantly
      greater and more varied psychiatric problems across adulthood.

PMID- 25749480
TI  - Understanding emotion and emotional scarring in recurrent depression.
AB  - BACKGROUND: A single-item assessment of sad mood after remission from MDD is
      predictive of relapse, yet the mechanisms that play a role in depressive relapse
      remain poorly understood. METHODS: In 283 patients, remitted from recurrent
      depression (DSM-IV-TR criteria; HAM-D17 score <= 10), we examined emotional
      scarring, that is, whether the number of previous depressive episodes was
      associated with higher levels of sad mood as assessed with a 1-item Visual
      Analogue Mood Scale (VAMS). We then fitted a cross-sectional multivariate
      regression model to predict sad mood levels, including the Dysfunctional Attitude
      Scale Version-A, cognitive reactivity (Leiden Index of Depression Sensitivity),
      Ruminative Response Scale, and Everyday Problem Checklist. RESULTS: Patients with
      greater numbers of prior episodes experienced higher levels of sad mood after
      remission. In multivariate regression, intensity of daily stress and
      dysfunctional beliefs were associated with the VAMS (Adj. R(2)=.091) although not
      over and above depressive symptomatology (Adj. R(2)=.114). Cognitive reactivity
      was not associated with sadness. CONCLUSIONS: Our finding that patients with more
      previous MDEs reported higher levels of sad mood while remitted could be
      indicative of emotional scarring. Dysfunctional beliefs and intensity of daily
      stress were associated with sad mood but not over and above residual symptoms.
      Thus, illness related characteristics especially are associated with sad mood
      after remission. More negative affect after remission could result in lower
      stress tolerance or more stress intensity could result in negative affect. Future
      studies should examine premorbid sadness in a longitudinal cohort, and should
      study the exact pathway from stress, affect, and cognition to relapse.

PMID- 25749481
TI  - Chronic stress exacerbates neuronal loss associated with secondary
      neurodegeneration and suppresses microglial-like cells following focal motor
      cortex ischemia in the mouse.
AB  - Post-stroke patients describe suffering from persistent and unremitting levels of
      distress. Using an experimental model of focal cortical ischemia in adult male
      C57BL/6 mice, we examined whether exposure to chronic stress could modify the
      development of secondary thalamic neurodegeneration (STND), which is commonly
      reported to be associated with impaired functional recovery. We were particularly
      focused on the modulatory role of microglia-like cells, as several clinical
      studies have linked microglial activation to the development of STND. One month
      following the induction of cortical ischemia we identified that numbers of
      microglial-like cells, as well as putative markers of microglial structural
      reorganization (Iba-1), complement processing (CD11b), phagocytosis (CD68), and
      antigen presentation (MHC-II) were all significantly elevated in response to
      occlusion. We further identified that these changes co-occurred with a decrease
      in the numbers of mature neurons within the thalamus. Occluded animals that were
      also exposed to chronic stress exhibited significantly lower levels of Iba-1
      positive cells and a reduced expression of Iba-1 and CD11b compared to the
      'occlusion-alone' group. Interestingly, the dampened expression of
      microglial/monocyte markers observed in stressed animals was associated with
      significant additional loss of neurons. These findings indicate that the process
      of STND can be negatively modified, potentially in a microglial dependent manner,
      by exposure to chronic stress. 

PMID- 25749482
TI  - Neutralization of colony-stimulating factor 1 receptor prevents sickness behavior
      syndrome by reprogramming inflammatory monocytes to produce IL-10.
AB  - Sickness behavior syndrome (SBS) as characterized by fatigue and depression
      impairs quality of life in patients with inflammatory diseases caused by
      infections and autoimmunity. Systemic engagement of CD40 in mice leads to an
      inflammatory syndrome with acute hepatitis, lymphadenopathy and development of
      SBS as evidenced by induction of sleep and weight loss. In the study presented
      here we show that the elimination of resident tissue macrophages in mice by
      antibody-mediated neutralization of colony-stimulating factor-1 receptor (CSF1R)
      did not prevent CD40 induced hepatitis, but conferred resistance to the
      development of SBS. The protective effect of CSF1R mAb on weight loss and
      behavior changes induced by CD40 activation coincided with the transformation of
      pro-inflammatory monocytes to IL-10 producing myeloid cells. In IL-10 knockout
      mice CSF1R neutralization failed to exert protection from the occurrence of SBS.
      This study establishes the unexpected key role of CSF1R in the polarization of
      inflammatory monocytes and thereby SBS in inflammatory liver diseases. 

PMID- 25749483
TI  - Predictive processing of pitch trends in newborn infants.
AB  - The notion of predictive sound processing suggests that the auditory system
      prepares for upcoming sounds once it has detected regular features within a
      sequence. Here we investigated whether predictive processes are operating at
      birth in the human auditory system. Event-related potentials (ERP) were recorded
      from healthy newborns to occasional ascending pitch steps occurring in the 2nd or
      the 5th position within trains of tones with otherwise monotonously descending
      pitch. If the trains were processed in a predictive manner only deviant pitch
      steps occurring in the later train position would elicit the discriminative
      mismatch response (MMR). Deviants delivered in the 5th but not in the 2nd
      position of the tone trains elicited a significant MMR response. These results
      suggest that newborns represent pitch trends within sound sequences and they
      process them in a predictive manner. This article is part of a Special Issue
      entitled SI: Prediction and Attention. 

PMID- 25749484
TI  - Introduction and validation of a less painful algorithm to estimate the
      nociceptive flexion reflex threshold.
AB  - The nociceptive flexion reflex (NFR) is a widely used tool to investigate spinal
      nociception for scientific and diagnostic purposes, but its clinical use is
      currently limited due to the painful measurement procedure, especially
      restricting its applicability for patients suffering from chronic pain disorders.
      Here we introduce a less painful algorithm to assess the NFR threshold.
      Application of this new algorithm leads to a reduction of subjective pain ratings
      by over 30% compared to the standard algorithm. We show that the reflex threshold
      estimates resulting from application of the new algorithm can be used
      interchangeably with those of the standard algorithm after adjusting for the
      constant difference between the algorithms. Furthermore, we show that the new
      algorithm can be applied at shorter interstimulus intervals than are commonly
      used with the standard algorithm, since reflex threshold values remain unchanged
      and no habituation effects occur when reducing the interstimulus interval for the
      new algorithm down to 3s. Finally we demonstrate the utility of the new algorithm
      to investigate the modulation of nociception through different states of
      attention. Taken together, the here presented new algorithm could increase the
      utility of the NFR for investigation of nociception in subjects who were
      previously not able to endure the measurement procedure, such as chronic pain
      patients. 

PMID- 25749485
TI  - The ethical challenges in rheumatology.
AB  - Ethical dilemmas arise with regularity, indeed daily, in the practice of
      rheumatology. As such, the practitioner must have the sensitivity and capacity to
      recognize them, reflect on their implications, and formulate responses directed
      at their mitigation. This article presents relevant ethical considerations (old
      and new) arising in the contemporary practice of rheumatology. A number of
      considerations stand out for their relevance to the rheumatic diseases.
      Conspicuous among these are the high costs associated with modern antirheumatic
      therapy, the complex relationship between physicians and the pharmaceutical
      industry, as well as challenges to the provision of care to patients suffering
      from complex chronic diseases. In this regard, patient autonomy is discussed, as
      is the need to insure for the provision of the time and resources for adequate
      patient education. The importance of such concerns goes beyond the patients'
      themselves extending to the future generation of physicians who we will educate. 

PMID- 25749486
TI  - Age at migration, language proficiency, and socioeconomic outcomes: evidence from
      Australia.
AB  - This study estimates the causal effects of language proficiency on the economic
      and social integration of Australian immigrants. Identifying the effects of
      languages on socioeconomic outcomes is inherently difficult owing to the
      endogeneity of language skills. Using the phenomenon that younger children learn
      languages more easily than older children, we construct an instrumental variable
      for language proficiency. To achieve this, we consider the age at arrival of
      immigrants who came as children from Anglophone and non-Anglophone countries. We
      find a significant positive effect of English proficiency on wages and promotions
      among adults who immigrated to Australia as children. Higher levels of English
      proficiency are associated with increased risk-taking, more smoking, and more
      exercise for men, but have considerable health benefits for women. English
      language proficiency has a significant influence on partner choice and a number
      of social outcomes, as well as on children's outcomes, including their levels of
      academic achievement. The results are robust to alternative specifications,
      including accounting for between-sibling differences and alternative measures of
      English skills. 

PMID- 25749487
TI  - Trends in the economic consequences of marital and cohabitation dissolution in
      the United States.
AB  - Mothers in the United States use a combination of employment, public transfers,
      and private safety nets to cushion the economic losses of romantic union
      dissolution, but changes in maternal labor force participation, government
      transfer programs, and private social networks may have altered the economic
      impact of union dissolution over time. Using nationally representative panels
      from the Survey of Income and Program Participation (SIPP) from 1984 to 2007, we
      show that the economic consequences of divorce have declined since the 1980s
      owing to the growth in married women's earnings and their receipt of child
      support and income from personal networks. In contrast, the economic consequences
      of cohabitation dissolution were modest in the 1980s but have worsened over time.
      Cohabiting mothers' income losses associated with union dissolution now closely
      resemble those of divorced mothers. These trends imply that changes in marital
      stability have not contributed to rising income instability among families with
      children, but trends in the extent and economic costs of cohabitation have likely
      contributed to rising income instability for less-advantaged children. 

PMID- 25749488
TI  - Juvenile salmon usage of the Skeena River estuary.
AB  - Migratory salmon transit estuary habitats on their way out to the ocean but this
      phase of their life cycle is more poorly understood than other phases. The
      estuaries of large river systems in particular may support many populations and
      several species of salmon that originate from throughout the upstream river. The
      Skeena River of British Columbia, Canada, is a large river system with high
      salmon population- and species-level diversity. The estuary of the Skeena River
      is under pressure from industrial development, with two gas liquefaction
      terminals and a potash loading facility in various stages of environmental review
      processes, providing motivation for understanding the usage of the estuary by
      juvenile salmon. We conducted a juvenile salmonid sampling program throughout the
      Skeena River estuary in 2007 and 2013 to investigate the spatial and temporal
      distribution of different species and populations of salmon. We captured six
      species of juvenile anadromous salmonids throughout the estuary in both years,
      and found that areas proposed for development support some of the highest
      abundances of some species of salmon. Specifically, the highest abundances of
      sockeye (both years), Chinook in 2007, and coho salmon in 2013 were captured in
      areas proposed for development. For example, juvenile sockeye salmon were 2-8
      times more abundant in the proposed development areas. Genetic stock assignment
      demonstrated that the Chinook salmon and most of the sockeye salmon that were
      captured originated from throughout the Skeena watershed, while some sockeye
      salmon came from the Nass, Stikine, Southeast Alaska, and coastal systems on the
      northern and central coasts of British Columbia. These fish support extensive
      commercial, recreational, and First Nations fisheries throughout the Skeena River
      and beyond. Our results demonstrate that estuary habitats integrate species and
      population diversity of salmon, and that if proposed development negatively
      affects the salmon populations that use the estuary, then numerous fisheries
      would also be negatively affected. 

PMID- 25749489
TI  - Repositioning chairs in benign paroxysmal positional vertigo: implications and
      clinical outcome.
AB  - The objective was to evaluate the clinical value of repositioning chairs in
      management of refractory benign paroxysmal positional vertigo (BPPV) and to study
      how different BPPV subtypes respond to treatment. We performed a retrospective
      chart review of 150 consecutive cases with refractory vertigo referred to our
      clinic within a 10-month period. The BPPV patients were managed with classical
      manual manoeuvres, the Epley Omniax((r)) rotator (EO) or the TRV chair (TRV). In
      addition, a comprehensive review of the literature was performed. BPPV was
      identified in 95 cases. The number of needed treatments for posterior
      canalolithiasis versus posterior cupulolithiasis, horizontal cupulolithiasis and
      multi-canal affection was significant (p < 0.01). Thirty-seven (38 %) patients
      required only one repositioning manoeuvre and the overall symptom relief was 91.7
      100 % after 3 treatments. Eleven patients (12 %) experienced relapse within the
      1/2-year follow-up period. Horizontal cupulolithiasis and multi-canal affection
      constituted the most resilient cases. The literature search identified 9
      repositioning chair studies. The EO and the TRV are highly valuable assets in
      diagnosis and management of BPPV of particularly complex and refractory cases.
      However, further validation is anticipated through controlled clinical trials.

PMID- 25749490
TI  - A single-item screening question for fear of recurrence in head and neck cancer.
AB  - Fear of recurrence (FoR) is the most frequent concern patients wish to discuss in
      head and neck review clinics. The aim of the study was to design a simple
      screening question on fear of recurrence to be incorporated into the University
      of Washington Quality of Life Questionnaire (UW-QOLv4), for use in clinical
      practice. A cross-sectional survey comprising 528 patients was conducted. 11 %
      selected the two most severe FoR categories. FoR responses correlated strongly
      (Spearman r s = -0.82) with the mean score of the seven items of the Fear of
      Recurrence Questionnaire. There was also a strong association with anxiety and
      mood dysfunction as measured from the UW-QOL, and with overall QOL. Patients more
      affected by FoR tended to be younger and post-radiotherapy or chemotherapy. The
      FoR screening question may be a useful addition to the UW-QOLv4 to help identify
      patients with significant FoR to receive extra support.

PMID- 25749491
TI  - Can we improve breast cancer mortality in Okinawa? Consensus of the 7th Okinawa
      Breast Oncology Meeting.
AB  - The rate of breast cancer mortality in Okinawa has gradually been increasing up
      to 2010. Now Okinawa has the second worst mortality rate in Japan, in part due to
      the enormous dietary changes resulting from the post-World War II US military
      occupation, high incidence of obesity, high non-optimal treatment rate, and low
      breast-cancer screening rate. To reduce breast cancer mortality in Okinawa, we
      established the Okinawa Breast Oncology Meeting (OBOM) in 2012. At the 7th OBOM
      held on January 10th, 2014, we discussed the breast cancer mortality in Okinawa
      focusing on lifestyle, breast cancer screening and optimal treatments. The
      Okinawan women who were overweight and/or obese during premenopausal and
      postmenopausal ages had a statistically significant higher risk of breast cancer
      development compared to those with non-overweight and/or obese women. The
      traditional diet of Okinawa consists of foods low in calories but rich in
      nutritional value. Therefore, we recommend Okinawan people not to forget the
      Okinawan traditional lifestyle, and to reduce their bodyweight to prevent breast
      cancer. One of the main goals of the OBOM is to raise breast cancer screening
      attendance rates to 50% (29.2% in 2010). We should standardize the quality
      control for breast cancer screening in Okinawa. It is important to continue
      enlightening the Okinawan population to receive optimal treatment. In addition,
      we are striving to establish systematic medical cooperation between the hospitals
      specializing in breast cancer treatment with rural hospitals. The OBOM group
      endeavors to contribute to the improvement of breast cancer mortality in Okinawa.

PMID- 25749492
TI  - Substrate elasticity modulates the responsiveness of mesenchymal stem cells to
      commitment cues.
AB  - Fate choices of stem cells are regulated in response to a complex array of
      biochemical and physical signals from their microenvironmental niche. Whereas the
      molecular composition and the role of mechanical niche cues have been extensively
      studied, relatively little is known about how both effectors act in concert to
      modulate stem cell fate. Here we utilized a recently developed artificial niche
      microarray platform to investigate whether the stiffness of a cell culture
      substrate influences how niche signaling factors exert their role on adipogenic
      differentiation of human mesenchymal stem cells (hMSC). We found that substrate
      stiffness imposes a strictly non-overlapping range of differentiation,
      highlighting the dominance of physical over the biochemical factors. At a given
      stiffness, a significant protein-dependent effect on adipogenic differentiation
      was observed. Furthermore, we show that synergistic interactions between proteins
      can also be driven by the substrate stiffness. Our results thus highlight the
      importance of considering the mechanical properties of a target tissue when
      investigating biochemical niche signals in vitro. 

PMID- 25749493
TI  - Agreement between physiotherapists rating scapular posture in multiple planes in
      patients with neck pain: Reliability study.
AB  - OBJECTIVE: Evaluation of scapular posture is an integral component of the
      clinical assessment of painful neck disorders. The aim of this study was to
      evaluate agreement between therapist judgements of scapula posture in multiple
      biomechanical planes in individuals with neck pain. DESIGN: Inter-therapist
      reliability study. SETTING: Research laboratory. PARTICIPANTS: Fifteen
      participants with chronic neck pain. MAIN OUTCOME MEASURES: Four physiotherapists
      recorded ratings of scapular orientation (relative to the thorax) in five
      different scapula postural planes (plane of scapula, sagittal plane, transverse
      plane, horizontal plane, and vertical plane) under four test conditions (at rest,
      and during three isometric shoulder conditions) in all participants. Inter
      therapist reliability was expressed using both generalized and paired kappa
      coefficient. RESULTS: Following adjustment for expected agreement and the high
      prevalence of neutral ratings (81%), on average both the generalised kappa (0.37)
      as well as Cohen's Kappa for the two therapist pairs (0.45 and 0.42) demonstrated
      only slight to moderate inter-therapist reliability. CONCLUSIONS: The findings
      suggest that ratings of scapular posture in individuals with neck pain by visual
      inspection has only slight to moderate reliability and should only be used in
      conjunction with other clinical tests when judging scapula function in these
      patients.

PMID- 25749494
TI  - Differences in delivery of respiratory treatments by on-call physiotherapists in
      mechanically ventilated children: a randomised crossover trial.
AB  - OBJECTIVES: To investigate differences, if any, in the delivery of respiratory
      treatments to mechanically ventilated children between non-respiratory on-call
      physiotherapists and specialist respiratory physiotherapists. SETTING:
      Paediatric, tertiary care hospital in the United Kingdom. PARTICIPANTS: 93
      children (aged between 3 days and 16 years), and 22 physiotherapists (10
      specialist respiratory physiotherapists) were recruited to the study.
      INTERVENTIONS: Recruited children received two physiotherapy treatments during a
      single day, one delivered by a non-respiratory physiotherapist, the other by a
      specialist respiratory physiotherapist in a randomised order. Selection, delivery
      and effects of techniques were recorded for each treatment. OUTCOME MEASURES:
      Primary outcomes were selection and application of treatment components.
      Secondary outcomes included respiratory effects (in terms of changes in flow,
      volume and pressure) of selected treatment components. RESULTS: Both non
      respiratory on-call physiotherapists and specialist respiratory physiotherapists
      used combinations of saline instillation, manual lung inflations, chest wall
      vibrations and endotracheal suction during treatments. However specialist
      respiratory physiotherapists used combinations of chest wall vibrations with
      suction, and recruitment manoeuvres, significantly more frequently than non
      respiratory on-call physiotherapists (92% vs 52%, and 87% vs 46% of treatments
      respectively, P<0.001). Chest wall vibrations delivered by non-respiratory on
      call physiotherapists were 15% less effective at increasing peak expiratory flow.
      CONCLUSION: Clinically important differences between non-respiratory and
      specialist respiratory physiotherapists' treatment outcomes may be related to
      differences in the selection and application of techniques. This suggests an
      important training need for non-respiratory on-call physiotherapists,
      particularly in the effective delivery of physiotherapy techniques. TRIAL
      REGISTRATION: Clinicaltrials.gov NCT01999426.

PMID- 25749495
TI  - Clinical effects of specialist and on-call respiratory physiotherapy treatments
      in mechanically ventilated children: A randomised crossover trial.
AB  - OBJECTIVES: The study investigated treatment outcomes when respiratory
      physiotherapy was delivered by non-respiratory on-call physiotherapists, compared
      with specialist respiratory physiotherapists. DESIGN: Prospective, randomised
      crossover trial. SETTING: Paediatric, tertiary care hospital in the United
      Kingdom. PARTICIPANTS: Mechanically ventilated children requiring two
      physiotherapy interventions during a single day were eligible. Twenty two
      physiotherapists (10 non-respiratory) and 93 patients were recruited.
      INTERVENTIONS: Patients received one treatment from a non-respiratory
      physiotherapist and another from a respiratory physiotherapist, in a randomised
      order. Treatments were individualised to the patients' needs, often including re
      positioning followed by manual lung inflations, chest wall vibrations and
      endotracheal suction. MAIN OUTCOME MEASURES: The primary outcome was respiratory
      compliance. Secondary outcomes included adverse physiological events and
      clinically important respiratory changes (according to an a priori definition).
      RESULTS: Treatments delivered to 63 patients were analysed. There were
      significant improvements to respiratory compliance (mean increase [95% confidence
      intervals], 0.07 and 0.08ml.cmH2O(-1).kg(-1) [0.01 to 0.14 and 0.04 to 0.13],
      p<0.01, for on-call and respiratory physiotherapists' treatments respectively).
      Case-by-case, there were fewer clinically important improvements following non
      respiratory physiotherapists' treatments compared with the respiratory
      physiotherapists' (n=27 [43%] versus n=40 [63%], p=0.03). Eleven adverse events
      occurred, eight following non-respiratory physiotherapists' treatments.
      CONCLUSIONS: Significant disparities exist in treatment outcomes when patients
      are treated by non-respiratory on-call physiotherapists, compared with specialist
      respiratory physiotherapists. There is an urgent need for targeted training
      strategies, or alternative service delivery models, to be explored. This should
      aim to address the quality of respiratory physiotherapy services, both during and
      outside of normal working hours. CLINICAL TRIAL REGISTRATION NUMBER:
      Clinicaltrials.gov, NCT01999426.

PMID- 25749496
TI  - ECDI-fixed allogeneic splenocytes combined with alpha1-antitrypsin prolong
      survival of rat renal allografts.
AB  - Pre- and post-transplant infusions of donor splenocytes treated with 1-ethyl-3
      (3'-dimethylaminopropyl)-carbodiimide (ECDI-SPs) induce donor-specific tolerance
      and prolong rat renal allograft survival. However, proinflammatory cytokine
      production during peritransplantation negates the effects of ECDI-SPs. Therefore,
      we reasoned that blocking proinflammatory cytokines would promote long-term ECDI
      SP-induced allograft survival. We therefore examined the effects of infusing ECDI
      SPs alone or in combination with a short course of alpha1-Antitrypsin (AAT) on
      the long-term outcomes of a rat kidney allograft model. The data showed that ECDI
      SPs+AAT promote renal allograft survival compared with ECDI-SPs alone. This
      effect was accompanied by expansion of Foxp3+ Tregs, enhanced alloantigen
      specific Treg function, and modulation of expression levels of proinflammatory
      cytokines IL-1beta, IL-6, TNF-alpha, and the anti-inflammatory cytokine IL-10. In
      conclusion, our strategy of combining ECDI-SPs and AAT provides a promising
      approach for inducing specific transplant tolerance.

PMID- 25749497
TI  - Thalidomide prevents cigarette smoke extract-induced lung damage in mice.
AB  - Chronic obstructive pulmonary disease (COPD) is characterized by a progressive
      airway obstruction that is not completely reversible and is mainly caused by
      smoking tobacco. COPD is a major cause of morbidity and mortality worldwide and
      there are currently no proven effective treatments. The pathogenesis of COPD
      involves several factors such as chronic inflammation, oxidative stress, and
      apoptosis. Cytokines play important roles in chronic inflammation. Thalidomide
      (Thal) has been used to treat multiple myeloma due to its inhibitory effects on
      IL-6-induced cell growth. We recently demonstrated that thalidomide (Thal) played
      important roles in cytokine-induced lung damage in a bleomycin-induced pulmonary
      fibrosis model in mice. We herein examined the preventative effects of Thal on
      cigarette smoke extract (CSE)-induced emphysematous changes in mice. We performed
      histological examinations and quantitative measurements of the expression of IL
      1beta and IL-6 mRNA, as well as apoptosis in CSE-induced mouse lung tissues
      treated with or without Thal. The results of the histological examination showed
      that Thal ameliorated CSE-induced emphysema in mice. It also inhibited the
      expression of IL-1beta and IL-6 mRNA in mouse lung tissues. Thal decreased
      apoptosis in the mouse lung. In vitro studies revealed that Thal decreased 1) the
      expression of IL-1beta and IL-6 in human lung epithelial cells, and 2) CSE
      induced apoptosis and the inhibition of cell growth, which may be the underlying
      mechanisms for the preventative effects of Thal on emphysema. These results
      provide a rationale for exploring the clinical use of Thal for COPD. 

PMID- 25749498
TI  - N-3-(oxododecanoyl)-L-homoserine lactone promotes the induction of regulatory T
      cells by preventing human dendritic cell maturation.
AB  - N-3-(Oxododecanoyl)-L-homoserine lactone (C12) is a small bacterial signaling
      molecule secreted by Pseudomonas aeruginosa (PA), which activates mammalian cells
      through TLR4-independent mechanisms. C12 acts as an immunosuppressant and it has
      been shown to modulate murine bone marrow-derived dendritic cell-mediated T
      helper 2 (Th2) cell polarizations in vitro. In the present study, we initially
      examined the impact of C12 on the maturation of human monocyte-derived dendritic
      cells (Mo-DCs) and the induction of regulatory T-cells (iTregs) in culture. Our
      findings demonstrate that C12-treated Mo-DCs failed to undergo lipopolysaccharide
      (LPS)-induced maturation. At the molecular level, C12 blocked the upregulation of
      surface molecules, including CD11c, HLA-DR, CD40, and CD80, and it switched to an
      interleukin (IL)-10(high), IL-12p70(low) phenotype. Moreover, C12 selectively
      inhibited the capacity of Mo-DCs to stimulate the proliferation of allogeneic
      CD4(+) T-cells. Otherwise, the C12-treated Mo-DCs promoted the generation of
      CD4(+)CD25(+)Foxp3(+)-induced regulatory T-cells (iTregs) and enhanced their IL
      10 and transforming growth factor (TGF)-beta production associated with reduced
      interferon (IFN)-gamma and IL-12p70 production. These findings provide new
      insights towards understanding the persistence of chronic inflammation in PA
      infection. 

PMID- 25749499
TI  - The short-term effects of graded activity versus physiotherapy in patients with
      chronic low back pain: A randomized controlled trial.
AB  - BACKGROUND: Chronic low back pain is one of the most common problematic health
      conditions worldwide and is highly associated with disability, quality of life,
      emotional changes, and work absenteeism. Graded activity programs, based on
      cognitive behavioral therapy, and exercises are common treatments for patients
      with low back pain. However, recent evidence has shown that there is no evidence
      to support graded activity for patients with chronic nonspecific low back pain.
      AIM: to compare the effectiveness of graded activity and physiotherapy in
      patients with chronic nonspecific low back pain. METHODS: A total of 66 patients
      with chronic nonspecific low back pain were randomized to perform either graded
      activity (moderate intensity treadmill walking, brief education and strength
      exercises) or physiotherapy (strengthening, stretching and motor control). These
      patients received individual sessions twice a week for six weeks. The primary
      measures were intensity of pain (Pain Numerical Rating Scale) and disability
      (Rolland Morris Disability Questionnaire). RESULTS: After six weeks, significant
      improvements have been observed in all outcome measures of both groups, with a
      non-significant difference between the groups. For intensity of pain (mean
      difference = 0.1 points, 95% confidence interval [CI] = -1.1-1.3) and disability
      (mean difference = 0.8 points, 95% confidence interval [CI] = -2.6-4.2). No
      differences were found in the remaining outcomes. CONCLUSION: The results of this
      study suggest that graded activity and physiotherapy showed to be effective and
      have similar effects for patients with chronic nonspecific low back pain.

PMID- 25749500
TI  - Correction: Mutation rules and the evolution of sparseness and modularity in
      biological systems.

PMID- 25749501
TI  - Intermittent fasting results in tissue-specific changes in bioenergetics and
      redox state.
AB  - Intermittent fasting (IF) is a dietary intervention often used as an alternative
      to caloric restriction (CR) and characterized by 24 hour cycles alternating ad
      libitum feeding and fasting. Although the consequences of CR are well studied,
      the effects of IF on redox status are not. Here, we address the effects of IF on
      redox state markers in different tissues in order to uncover how changes in
      feeding frequency alter redox balance in rats. IF rats displayed lower body mass
      due to decreased energy conversion efficiency. Livers in IF rats presented
      increased mitochondrial respiratory capacity and enhanced levels of protein
      carbonyls. Surprisingly, IF animals also presented an increase in oxidative
      damage in the brain that was not related to changes in mitochondrial
      bioenergetics. Conversely, IF promoted a substantial protection against oxidative
      damage in the heart. No difference in mitochondrial bioenergetics or redox
      homeostasis was observed in skeletal muscles of IF animals. Overall, IF affects
      redox balance in a tissue-specific manner, leading to redox imbalance in the
      liver and brain and protection against oxidative damage in the heart. 

PMID- 25749502
TI  - Combination of granulocyte colony-stimulating factor and erythropoietin improves
      outcomes of patients with decompensated cirrhosis.
AB  - BACKGROUND & AIMS: Patients with decompensated cirrhosis have significantly
      reduced survival without liver transplantation. Granulocyte colony-stimulating
      factor (G-CSF) has been shown to increase survival in patients with acute-on
      chronic liver failure, and erythropoietin promoted hepatic regeneration in animal
      studies. We performed a double-blind, randomized, placebo-controlled trial to
      determine whether co-administration of these growth factors improved outcomes for
      patients with advanced cirrhosis. METHODS: In a prospective study, consecutive
      patients with decompensated cirrhosis seen at the Institute of Liver and Biliary
      Sciences, New Delhi (from May 2011 through June 2012) were randomly assigned to
      groups given subcutaneous G-CSF (5 MUg/kg/d) for 5 days and then every third day
      (12 total doses), along with subcutaneous darbopoietin alpha(40 mcg/wk) for 4
      weeks (GDP group, n = 29), or only placebos (control group, n = 26). All patients
      also received standard medical therapy and were followed for 12 months. Histology
      was performed on liver biopsies. The primary end point was survival at 12 months.
      RESULTS: Baseline characteristics of patients were comparable; alcohol intake was
      the most common etiology of cirrhosis. A higher proportion of patients in the GDP
      group than controls survived until 12 months (68.6% vs 26.9%; P = .003). At 12
      months, Child-Turcotte Pugh scores were reduced by 48.6% in the GDP group and
      39.1% in the control group, from baseline (P = .001); Model for End Stage Liver
      Disease scores were reduced by 40.4% and 33%, respectively (P = .03). The need
      for large-volume paracentesis was significantly reduced in GDP group, compared
      with controls (P < .05). A lower proportion of patients in the GDP group
      developed septic shock (6.9%) during follow-up compared with controls (38.5%; P =
      .005). No major adverse events were observed in either group. CONCLUSIONS: In a
      single-center randomized trial, a significantly larger proportion of patients
      with decompensated cirrhosis given a combination of G-CSF and darbopoietin alpha
      survived for 12 months more than patients given only placebo. The combination
      therapy also reduced liver severity scores and sepsis to a greater extent than
      placebo. Clinicaltrials.gov ID: NCT01384565.

PMID- 25749503
TI  - Effect of testing for cancer on cancer- and venous thromboembolism (VTE)-related
      mortality and morbidity in patients with unprovoked VTE.
AB  - BACKGROUND: Venous thromboembolism (VTE) is a collective term for two conditions:
      deep vein thrombosis (DVT) and pulmonary embolism (PE). A proportion of patients
      with VTE have no underlying or immediately predisposing risk factors and the VTE
      is referred to as unprovoked. Unprovoked VTE can often be the first clinical
      manifestation of an underlying malignancy. This has raised the question of
      whether patients with an unprovoked VTE should be investigated for an underlying
      cancer. Treatment for VTE is different in cancer and non-cancer patients and a
      correct diagnosis would ensure that patients received the optimal treatment for
      VTE to prevent recurrence and further morbidity. Furthermore, an appropriate
      cancer diagnosis at an earlier, potentially curative stage could avoid the risk
      of cancer progression and thus lead to improvements in cancer-related mortality
      and morbidity. OBJECTIVES: To determine whether testing for undiagnosed cancer in
      patients with a first episode of unprovoked VTE (DVT or PE) is effective in
      reducing cancer and VTE-related mortality and morbidity and to establish which
      tests for cancer are most useful. SEARCH METHODS: The Cochrane Peripheral
      Vascular Diseases Group Trials Search Co-ordinator searched the Specialised
      Register (last searched January 2015) and the Cochrane Register of Studies (CRS)
      (2014, Issue 12). Clinical trials databases were searched. The reference lists of
      relevant articles were also checked. SELECTION CRITERIA: Randomised and quasi
      randomised trials in which patients with an unprovoked VTE were allocated to
      receive specific tests for cancer or clinically indicated tests only were
      eligible for inclusion in this review. Primary outcomes included all-cause
      mortality, cancer-related mortality and VTE-related mortality. DATA COLLECTION
      AND ANALYSIS: Selection of the studies, quality assessment and data extraction
      were completed independently by two review authors. Any disagreements were
      resolved by discussion. MAIN RESULTS: Two studies with a combined total of 396
      patients met the inclusion criteria for this review. Both studies assessed the
      effect of testing for cancer versus clinically indicated tests only in patients
      with an unprovoked VTE. The quality of the evidence was moderate because although
      the studies were judged to be at low or unclear risk of bias, there was concern
      that the studies were small as reflected in the wide confidence intervals (CIs).
      Pooled analysis showed that testing for cancer was consistent with either a
      benefit or no benefit on cancer-related mortality (odds ratio (OR) 0.49, 95% CI
      0.15 to 1.67, P = 0.26). One study showed that, overall, malignancies were less
      advanced in patients belonging to the extensive screening group than in patients
      of the control group (64% versus 20%, P = 0.047) and that tested patients were
      diagnosed earlier than untested patients (mean 1 month versus 11.6 months to
      cancer diagnosis from the time of diagnosis of VTE). Standard deviations were not
      provided for time to diagnosis, so it was not possible to perform an independent
      statistical analysis on this association. Neither study measured all-cause
      mortality, VTE-related morbidity and mortality, side effects of anticoagulation,
      side effects of cancer tests or patient satisfaction. AUTHORS' CONCLUSIONS:
      Testing for cancer in patients with idiopathic VTE leads to earlier diagnosis of
      cancer at an earlier stage of the disease. However, there is currently
      insufficient evidence to draw definitive conclusions concerning the effectiveness
      of testing for undiagnosed cancer in patients with a first episode of unprovoked
      VTE (DVT or PE) in reducing cancer and VTE-related morbidity and mortality. The
      results are imprecise and could be consistent with either harm or benefit.
      Further good-quality large-scale randomised controlled trials are required before
      firm conclusions can be made.

PMID- 25749504
TI  - Increase in developmental instability in a field-collected Chironomus population
      maintained under laboratory conditions.
AB  - In order to be a relevant indicator of exposure towards teratogenic stressors,
      morphological defects should not be passed on to the next generation. In this
      study, we compare morphological variations in Chironomids collected from a
      contaminated river stretch with those of their progeny, reared in uncontaminated
      sediment under laboratory conditions. We focused on mentum defects (deformities,
      fluctuating asymmetry and mean shape change), measured by geometric
      morphometrics. We observed no significant variation in deformity rate between the
      parental generation and its progeny. On the contrary, we observed a significant
      increase in fluctuating asymmetry and a significant decrease in mentum centroid
      size in the offspring. Our results suggest that shape defects are not caused by
      direct exposure to teratogenic stressors alone. We propose four hypotheses to
      explain this: (a) teratogenic contaminants are present in egg-clutches, (b)
      contaminants at the sampling site have mutagenic effects, (c) costs of tolerance,
      and (d) contamination-induced genetic impoverishment.

PMID- 25749505
TI  - Pesticides for apicultural and/or agricultural application found in Belgian honey
      bee wax combs.
AB  - In a Belgian pilot study honey bee wax combs from ten hives were analyzed on the
      presence of almost 300 organochlorine and organophosphorous compounds by LC-MS/MS
      and GC-MS/MS. Traces of 18 pesticides were found and not a single sample was free
      of residues. The number of residues found per sample ranged from 3 to 13, and the
      pesticides found could be categorized as (1) pesticides for solely apicultural
      (veterinary) application, (2) pesticides for solely agricultural (crop
      protection) application, (3) pesticides for mixed agricultural and apicultural
      (veterinary) application. The frequencies and quantities of some environmental
      pollutants bear us high concerns. Most alarming was the detection of lindane
      (gamma-HCH) and dichlorodiphenyltrichloroethane (including its breakdown product
      dichlorodiphenyldichloroethylene), two insecticides that are banned in Europe.
      The present comprehensive residue analysis, however, also reveals residues of
      pesticides never found in beeswax before, i.e. DEET, propargite and bromophos. 

PMID- 25749506
TI  - Condition and Health of Rufous Bush Robin (Cercotrichas galactotes) Nestlings in
      a Polluted Oasis Habitat in Southern Tunisia.
AB  - We investigated whether the proximity to the Gabes-Ghannouche factory complex of
      phosphate treatment, in south-eastern Tunisia, was associated with notable
      changes in the condition and health of Rufous bush robin (Cercotrichas
      galactotes) nestlings hatched in the neighbouring oasis habitat. Results
      demonstrated that excrements of nestlings hatched in one oasis close to the
      factory complex contained higher concentrations of lead and zinc than the
      excrements of nestlings from one oasis situated 20 km away. Furthermore, when
      effects of age and nestling number in the nest were controlled, nestlings hatched
      near the factory complex showed reduced tarsus length, rectrix length,
      haematocrit level and haemoglobin concentration, but higher levels of fluctuating
      asymmetry compared to those from the more distant oasis. Overall, results suggest
      that the proximity to the factory complex was associated with increased exposure
      to metals and deterioration in nestling condition and development. 

PMID- 25749507
TI  - Hydrochemistry indicating groundwater contamination and the potential fate of
      chlorohydrocarbons in combined polluted groundwater: a case study at a
      contamination site in North China.
AB  - Groundwater contamination characteristics and the potential fate of
      chlorohydrocarbons were investigated at a combined polluted groundwater site in
      North China. Groundwater chemistry and (2)D and (18)O isotope compositions
      indicated that high salination of groundwater was related with chemical
      pollution. The elevated salinity plume was consistent with the domain where
      typical chlorohydrocarbon contaminants occurred. The concentrations of heavy
      metals, oxidation-reduction potential, and pH in organic polluted areas
      significantly differed from those in peripheral (background) areas, indicating
      modified hydrochemistry possibly resulting from organic pollution. Under the
      presented redox conditions of groundwater, monochlorobenzene oxidation may have
      occurred when the trichlorohydrocarbons underwent reductive dechlorination. These
      findings suggested that inorganic hydrochemistry effectively indicated the
      occurrence of chemical contamination in groundwater and the potential fate of
      chlorohydrocarbons.

PMID- 25749508
TI  - Effects of the lipid regulating drug clofibric acid on PPARalpha-regulated gene
      transcript levels in common carp (Cyprinus carpio) at pharmacological and
      environmental exposure levels.
AB  - In mammals, the peroxisome proliferator-activated receptor alpha (PPARalpha)
      plays a key role in regulating various genes involved in lipid metabolism, bile
      acid synthesis and cholesterol homeostasis, and is activated by a diverse group
      of compounds collectively termed peroxisome proliferators (PPs). Specific PPs
      have been detected in the aquatic environment; however little is known on their
      pharmacological activity in fish. We investigated the bioavailability and
      persistence of the human PPARalpha ligand clofibric acid (CFA) in carp, together
      with various relevant endpoints, at a concentration similar to therapeutic levels
      in humans (20mg/L) and for an environmentally relevant concentration (4MUg/L).
      Exposure to pharmacologically-relevant concentrations of CFA resulted in
      increased transcript levels of a number of known PPARalpha target genes together
      with increased acyl-coA oxidase (Acox1) activity, supporting stimulation of lipid
      metabolism pathways in carp which are known to be similarly activated in mammals.
      Although Cu,Zn-superoxide dismutase (Sod1) activity was not affected, mRNA levels
      of several biotransformation genes were also increased, paralleling previous
      reports in mammals and indicating a potential role in hepatic detoxification for
      PPARalpha in carp. Importantly, transcription of some of these genes (and Acox1
      activity) were affected at exposure concentrations comparable with those reported
      in effluent discharges. Collectively, these data suggest that CFA is
      pharmacologically active in carp and has the potential to invoke PPARalpha
      related responses in fish exposed in the environment, particularly considering
      that CFA may represent just one of a number of PPAR-active compounds present to
      which wild fish may be exposed. 

PMID- 25749510
TI  - Double-strand breaks from a radical commonly produced by DNA-damaging agents.
AB  - Double-strand breaks are widely accepted to be the most toxic form of DNA damage.
      Molecules that produce double-strand breaks via a single chemical event are
      typically very cytotoxic and far less common than those that form single-strand
      breaks. It was recently reported that a commonly formed C4'-radical produces
      double-strand breaks under aerobic conditions. Experiments described herein
      indicate that a peroxyl radical initiates strand damage on the complementary
      strand via C4'-hydrogen atom abstraction. Inferential evidence suggests that a
      C3'-peroxyl radical induces complementary strand damage more efficiently than
      does a C4'-peroxyl radical. Complementary strand hydrogen atom abstraction by the
      peroxyl radical is efficiently quenched by thiols. This mechanism could
      contribute to the higher than expected yield of double-strand breaks produced by
      ionizing radiation. 

PMID- 25749511
TI  - The IL-6/gp130/STAT3 signaling axis: recent advances towards specific inhibition.
AB  - Interleukin-6 has long been recognized as a prototypic pro-inflammatory cytokine
      that is involved in the pathogenesis of all inflammatory diseases. Activation of
      the gp130 homodimer by IL-6 leads to the initiation of Jak/STAT signaling, a
      pathway that is often constitutively switched on in inflammatory malignancies.
      However, a plethora of studies in the last decade has convincingly shown that
      only signaling via the soluble IL-6R (trans-signaling) accounts for the
      deleterious effects of IL-6, whereas classic signaling via the membrane-bound
      receptor is essential for the regenerative and anti-bacterial effects of IL-6
      (classic signaling). In this review, we highlight recent developments in the
      field of IL-6 research, and specifically focus on advances towards a safe and
      specific inhibition of IL-6 trans-signaling. 

PMID- 25749512
TI  - [Evidence-based medicine: Analysis of the randomized trial "imiquimod vs. surgery
      for basal cell carcinoma"].

PMID- 25749509
TI  - Pharmacological options for the management of refractory cancer pain-what is the
      evidence?
AB  - Refractory cancer pain that does not respond to standard opioid and/or co
      analgesic therapy occurs in 10-20 % of patients. Risk factors include young age,
      neuropathic pain type, incident pain, psychological distress, previous opioid
      use, high tolerance, a history of addiction and impaired cognition. The
      management of patients with refractory pain remains a challenge. Treatment
      options include opioid manipulation (parenteral delivery, rotation, combination,
      methadone and buprenorphine), non-opioids and co-analgesics (paracetamol, non
      steroidal anti-inflammatory agents, antidepressants and anticonvulsants), NMDA
      receptor antagonists, cannabinoids, lignocaine and corticosteroids. The evidence
      of benefit for any of these agents is weak, and each additional agent increases
      the risk of adverse events. Evidence-based guidelines cannot, therefore, be
      developed at present. New approaches are recommended including targeted opioid
      therapy, multimodal analgesia, a goal-oriented approach to pain management and
      increasing use of the multidisciplinary team and support services. 

PMID- 25749513
TI  - [Advancement cheek flap for nasal sidewall defects].
AB  - BACKGROUND: The nasal sidewall and adjacent cheek are frequent sites of cutaneous
      tumour. The aim of this study is to present an advancement-rotation cheek flap
      technique for nasal sidewall and paranasal cheek defects. PATIENTS AND METHODS:
      This is a retrospective, non-comparative study of patients undergoing a cheek
      advancement-rotation flap for nasal sidewall and paranasal cheek defects between
      September 2008 and October 2012. Sex, age, histological type of the excised
      lesion, method of anaesthesia, size of the defects, any occurrence of
      complications and results were compiled from the medical record. RESULTS: Eleven
      patients with a mean age of 66 years were included. For 10 patients, the tumour
      was a basal cell carcinoma and in one case was a squamous cell carcinoma. The
      defects were located in the nasal sidewall and paranasal cheek in four cases, the
      paranasal cheek/lower eyelid in five cases and in the nasal sidewall, anterior
      cheek and lower eyelid in two cases. All but one had surgery under a local
      anaesthetic. No patients presented post-surgical complications. One patient had a
      subcutaneous granuloma which subsequently subsided completely. The aesthetic
      result was good: two of the 11 patients had a marked nasolabial fold, one patient
      had a mild cutaneous deformity due to flap movement under eyelid. No recurrence
      of carcinoma was observed during follow-up of between 14 and 40 months.
      CONCLUSION: This flap should be considered for defects measuring under 3 cm on
      all or part of the nasal sidewall, paranasal cheek and lower eyelid fold.

PMID- 25749515
TI  - The influence of marital status on stage at diagnosis and survival of patients
      with colorectal cancer.
AB  - Marital status was found to be an independent prognostic factor for survival in
      various cancer types, but it hasn't been fully studied in colorectal cancer
      (CRC). The Surveillance, Epidemiology and End Results database was used to
      compare survival outcomes with marital status in each stage. In total, 112, 776
      eligible patients were identified. Patients in the widowed group were more
      frequently elderly women, more common of colon cancer, and more stage I/II in
      tumor stage (P < 0.001), but the surgery rate was comparable to that for the
      married group (94.72% VS 94.10%). Married CRC patients had better 5year cause
      specific survival (CSS) than those unmarried (P < 0.05). Further analysis showed
      that widowed patients always presented the lowest CSS compared with that of
      other' group. Widowed patients had 5% reduction 5-year CSS compared with married
      patients at stage I (94.8% vs 89.8%, P < 0.001), 9.4% reduction at stage II
      (85.9% vs 76.5%, P < 0.001), 16.7% reduction at stage III (70.6% vs 53.9%, P <
      0.001) and 6.2% reduction at stage IV(14.4% VS 8.2%, P < 0.001). These results
      showed that unmarried patients were at greater risk of cancer specific mortality.
      Despite favorable clinicpathological characteristics, widowed patients were at
      highest risk of death compared with other groups. 

PMID- 25749514
TI  - DC120, a novel AKT inhibitor, preferentially suppresses nasopharyngeal carcinoma
      cancer stem-like cells by downregulating Sox2.
AB  - Side population (SP) contains cancer stem-like cells (CSLCs). In this study, we
      characterized SP cells from nasopharyngeal carcinoma (NPC) cell lines and found
      that SP cells had a higher self-renewal ability in vitro and greater
      tumorigenicity in vivo. The AKT pathway was activated in NPC SP cells. DC120, a 2
      pyrimidyl-5-amidothiazole inhibitor of the ATP binding site of AKT, inhibited
      phosphorylation of FKHRL1 and GSK-3beta. DC120 inhibited SP fraction, the sphere
      forming ability in vitro and growth of primary xenografts as well as secondary
      xenografts' tumor recurrence. This inhibition was accompanied by reduced
      expression of stem-related gene Sox2 due to induction of p27 and miR-30a. A
      combination of DC120 and CDDP more effectively inhibited NPC cells compared with
      monotherapy in vitro and in vivo. Clinical evaluation of DC120 is warranted. 

PMID- 25749516
TI  - ColoLipidGene: signature of lipid metabolism-related genes to predict prognosis
      in stage-II colon cancer patients.
AB  - Lipid metabolism plays an essential role in carcinogenesis due to the
      requirements of tumoral cells to sustain increased structural, energetic and
      biosynthetic precursor demands for cell proliferation. We investigated the
      association between expression of lipid metabolism-related genes and clinical
      outcome in intermediate-stage colon cancer patients with the aim of identifying a
      metabolic profile associated with greater malignancy and increased risk of
      relapse. Expression profile of 70 lipid metabolism-related genes was determined
      in 77 patients with stage II colon cancer. Cox regression analyses using c-index
      methodology was applied to identify a metabolic-related signature associated to
      prognosis. The metabolic signature was further confirmed in two independent
      validation sets of 120 patients and additionally, in a group of 264 patients from
      a public database. The combined analysis of these 4 genes, ABCA1, ACSL1, AGPAT1
      and SCD, constitutes a metabolic-signature (ColoLipidGene) able to accurately
      stratify stage II colon cancer patients with 5-fold higher risk of relapse with
      strong statistical power in the four independent groups of patients. The
      identification of a group of 4 genes that predict survival in intermediate-stage
      colon cancer patients allows delineation of a high-risk group that may benefit
      from adjuvant therapy, and avoids the toxic and unnecessary chemotherapy in
      patients classified as low-risk group. 

PMID- 25749517
TI  - Inhibition of PI3K/AKT/mTOR axis disrupts oxidative stress-mediated survival of
      melanoma cells.
AB  - Elevated oxidative stress in cancer cells contributes to hyperactive
      proliferation and enhanced survival, which can be exploited using agents that
      increase reactive oxygen species (ROS) beyond a threshold level. Here we show
      that melanoma cells exhibit an oxidative stress phenotype compared with normal
      melanocytes, as evidenced by increased total cellular ROS, KEAP1/NRF2 pathway
      activity, protein damage, and elevated oxidized glutathione. Our overall
      objective was to test whether augmenting this high oxidative stress level in
      melanoma cells would inhibit their dependence on oncogenic PI3K/AKT/mTOR-mediated
      survival. We report that NexrutineR augmented the constitutively elevated
      oxidative stress markers in melanoma cells, which was abrogated by N-acetyl
      cysteine (NAC) pre-treatment. NexrutineR disrupted growth homeostasis by
      inhibiting proliferation, survival, and colony formation in melanoma cells
      without affecting melanocyte cell viability. Increased oxidative stress in
      melanoma cells inhibited PI3K/AKT/mTOR pathway through disruption of mTORC1
      formation and phosphorylation of downstream targets p70S6K, 4EBP1 and rpS6. NAC
      pre-treatment reversed inhibition of mTORC1 targets, demonstrating a ROS
      dependent mechanism. Overall, our results illustrate the importance of disruption
      of the intrinsically high oxidative stress in melanoma cells to selectively
      inhibit their survival mediated by PI3K/AKT/mTOR. 

PMID- 25749518
TI  - ZBRK1, a novel tumor suppressor, activates VHL gene transcription through
      formation of a complex with VHL and p300 in renal cancer.
AB  - Inactivation or mutation of the VHL gene causes various tumors, including clear
      cell renal cell carcinoma (ccRCC). In the present study, we identified ZBRK1 as a
      novel VHL interacting protein by yeast two-hybrid screening, and found a single
      ZBRK1-binding site located in the VHL promoter region. Ectopic expression of
      ZBRK1 increases transcriptional activity of the VHL, whereas the depletion of
      endogenous ZBRK1 by shRNA leads to reduction of VHL expression. We also
      demonstrate that the inhibition of VEGF transcription by ZBRK1 overexpression is
      dependent on VHL/HIF pathway. Moreover, VHL is confirmed to serve as a bridge
      component for the association of ZBRK1 and p300, which leads to an increase in
      ZBRK1 transcriptional activity in the VHL promoter. We further provide striking
      evidences that ZBRK1 acts as a tumor suppressor in renal carcinoma by a variety
      of in vitro and in vivo assays, and ZBRK1 may represent a molecular marker to
      distinguish patients with ccRCC at high risk from those with a better survival
      prognosis. Taken together, these findings suggest that ZBRK1 suppresses renal
      cancer progression perhaps by regulating VHL expression. 

PMID- 25749519
TI  - NF-kappaB-mediated miR-124 suppresses metastasis of non-small-cell lung cancer by
      targeting MYO10.
AB  - Recently, dysregulation of microRNAs plays a critical role in cancer metastasis.
      Here, an in vivo selection approach was used to generate highly aggressive NSCLC
      sub-cell lines followed by comparing the microRNAs expression using microarrays.
      miR-124 was notably deregulated in both highly invasive sub-cell lines and node
      positive NSCLC specimens. Over-expression of miR-124 robustly attenuated
      migration and metastatic ability of the aggressive cells. MYO10 was subsequently
      identified as a novel functional downstream target of miR-124, and was up
      regulated in node-positive NSCLC tissues. Knockdown of MYO10 inhibited cell
      migration, whereas forced MYO10 expression markedly rescued miR-124-mediated
      suppression of cell metastasis. Additionally, we found an activated NF-kappaB
      centered inflammatory loop in the highly aggressive cells leading to down
      regulation of miR-124. These results suggest that NF-kappaB-regulated miR-124
      targets MYO10, inhibits cell invasion and metastasis, and is down-regulated in
      node-positive NSCLC.

PMID- 25749520
TI  - Leukemia inhibitory factor receptor is a novel immunomarker in distinction of
      well-differentiated HCC from dysplastic nodules.
AB  - Differential diagnosis of well-differentiated hepatocellular carcinoma (WD-HCC)
      and high-grade dysplastic nodules (HGDNs) represents a challenge for
      pathologists. Several immunohistochemistry markers have been identified to
      distinguish hepatocellular carcinoma (HCC) from HGDNs. However, sensitivity or
      specificity of the individual marker is still limited. In this study, we analyzed
      dynamic alteration of leukemia inhibitory factor receptor (LIFR) and CD34 during
      hepatocarcinogenesis from dysplastic nodules to small HCC. The diagnostic
      performance of LIFR and CD34 combination in WD-HCC and HGDNs was investigated by
      logistic regression models and validated in an independent validation cohort.
      LIFR was decreased and CD34 was increased along with stepwise progression of
      hepatocarcinogenesis from low-grade dysplastic nodules (LGDNs) to small HCC. The
      sensitivity and specificity of the LIFR and CD34 combination for WD-HCC detection
      were 93.5% and 90.5%, respectively. In addition, colony formation assay was used
      to explore the role of LIFR in tumorigenesis. Silencing of LIFR could
      significantly promote colony formation of HCC cells, whereas ectopic
      overexpression of LIFR resulted in impaired ability of colony formation of HCC
      cells. These findings indicate that LIFR and CD34 combination may be used as an
      available differential diagnostic model for WD-HCC from HGDNs in clinical
      practice. 

PMID- 25749521
TI  - TNKS1BP1 functions in DNA double-strand break repair though facilitating DNA-PKcs
      autophosphorylation dependent on PARP-1.
AB  - TNKS1BP1 was originally identified as an interaction protein of tankyrase 1,
      which belongs to the poly(ADP-ribose) polymerase (PARP) superfamily. PARP members
      play important roles for example in DNA repair, telomere stability and mitosis
      regulation. Although the TNKS1BP1 protein was considered to be a poly(ADP
      ribosyl)ation acceptor of tankyrase 1, its function is still unknown. Here we
      firstly identified that TNKS1BP1 was up-regulated by ionizing radiation (IR) and
      the depletion of TNKS1BP1 significantly sensitized cancer cells to IR. Neutral
      comet assay, pulsed-field gel electrophoresis, and gammaH2AX foci analysis
      indicated that TNKS1BP1 is required for the efficient repair of DNA double-strand
      breaks (DSB). The TNKS1BP1 protein was demonstrated to interact with DNA
      dependent protein kinase (DNA-PKcs) and poly(ADP-ribose) polymerase 1 (PARP-1),
      by co-immunoprecipitation analysis. Moreover, TNKS1BP1 was shown to promote the
      association of PARP-1 and DNA-PKcs. Overexpression of TNKS1BP1 induced the
      autophosphorylation of DNA-PKcs/Ser2056 in a PARP-1 dependent manner, which
      contributed to an increased capability of DNA DSB repair. Inhibition of PARP-1
      blocked the TNKS1BP1-mediated DNA-PKcs autophosphorylation and attenuated the
      PARylation of DNA-PKcs. TNKS1BP1 is a newly described component of the DNA DSB
      repair machinery, which provides much more mechanistic evidence for the rationale
      of developing effective anticancer measures by targeting PARP-1 and DNA-PKcs. 

PMID- 25749522
TI  - Computational prediction and experimental validation of a novel synthesized pan
      PIM inhibitor PI003 and its apoptosis-inducing mechanisms in cervical cancer.
AB  - PIM protein family, short-lived serine/threonine kinases (PIM1, PIM2 and PIM3),
      are weak oncogenes but contribute to tumorigenesis as cancer targets. Thus,
      design of a novel pan-PIM inhibitor is still a challenge for current cancer drug
      discovery. Herein, we used a Naive Bayesian model to construct the PIM network
      and identified Bad and Hsp90 to interact with PIMs. Then, we screened a series of
      candidate small-molecule compounds targeting PIMs, and subsequently synthesized a
      novel small-molecule compound PI003 with remarkable anti-proliferative activities
      in cervical cancer cells. Moreover, we found that PI003 induced apoptosis via the
      death-receptor and mitochondrial pathways by targeting PIMs and affecting Bad and
      Hsp90. Combined with microRNA microarray analyses, we demonstrated that some
      microRNAs such as miR-1296 and miR-1299 could affect PIM1-STAT3 pathway in PI003
      induced apoptosis. Finally, we reported that PI003 had remarkable anti-tumor
      activity and apoptosis-inducing effect in in vivo mouse model. In conclusion,
      these results demonstrate that PI003, as a novel synthesized pan-PIM inhibitor,
      induces the death-receptor and mitochondrial apoptosis involved in microRNA
      regulation, and also possessed remarkable anti-tumor activity and apoptosis
      inducing effect in vivo. Thus, these findings would shed light on discovering
      more potential new small-molecule pan-PIM inhibitors in future cervical cancer
      therapy.

PMID- 25749523
TI  - Treatment-induced cell cycle kinetics dictate tumor response to chemotherapy.
AB  - Chemotherapy fails to provide durable cure for the majority of cancer patients.
      To identify mechanisms associated with chemotherapy resistance, we identified
      genes differentially expressed before and after chemotherapeutic treatment of
      breast cancer patients. Treatment response resulted in either increased or
      decreased cell cycle gene expression. Tumors in which cell cycle gene expression
      was increased by chemotherapy were likely to be chemotherapy sensitive, whereas
      tumors in which cell cycle gene transcripts were decreased by chemotherapy were
      resistant to these agents. A gene expression signature that predicted these
      changes proved to be a robust and novel index that predicted the response of
      patients with breast, ovarian, and colon tumors to chemotherapy. Investigations
      in tumor cell lines supported these findings, and linked treatment induced cell
      cycle changes with p53 signaling and G1/G0 arrest. Hence, chemotherapy
      resistance, which can be predicted based on dynamics in cell cycle gene
      expression, is associated with TP53 integrity. 

PMID- 25749524
TI  - A direct plasma assay of circulating microRNA-210 of hypoxia can identify early
      systemic metastasis recurrence in melanoma patients.
AB  - Circulating cell-free(cf) microRNAs (miRNAs) have been reported to exist in
      plasma. MicroRNA-210(miR-210) is known to play important roles in the tumor
      hypoxic state. We hypothesized that the expression levels of cf-miR-210 in plasma
      would predict early clinical recurrence in melanoma patients. A direct miRNA
      assay on plasma (RT-qPCR-DP) was developed to improve cf-miRNA assay logistics,
      eliminate RNA extraction, and reduce specimen amount required. RNA was extracted
      from formalin-fixed paraffin-embedded (FFPE) melanoma tissues (n = 108) and
      assessed by RT-qPCR. Plasma (10 MUl; n = 264) was procured from AJCC Stage III/IV
      patients in phase III clinical trials. A RT-qPCR-DP was performed to detect cf
      miR-210. MiR-210 was significantly higher in metastatic tumors compared to
      primary tumors. Cf-miR-210 was significantly higher in melanoma patients versus
      healthy donor controls. In serial bloods within individual patients, cf-miR-210 <
      3 months prior to disease recurrence significantly increased compared to baseline
      levels (p = 0.012). ROC curve analysis demonstrated that patients with elevated
      cf-miR-210 were more likely to have disease recurrence. Moreover, cf-miR-210
      increase significantly correlated with poorer prognosis (p < 0.001). Lactate
      dehydrogenase (LDH) level was also assessed within patients, and the AIC values
      for proportional hazards regression models of cf-miR-210(120.01) and LDH (122.91)
      demonstrated that cf-miR-210 is a better recurrence indicator. We concluded
      enhanced cf-miR-210 provides identification of early systemic melanoma
      recurrence. 

PMID- 25749526
TI  - Further validation of the Multiple Sclerosis Self-Efficacy Scale.
AB  - PURPOSE: This study examined the factorial and construct validity of the Multiple
      Sclerosis Self-Efficacy (MSSE) Scale in two samples of people with multiple
      sclerosis (MS). METHOD: Two samples (n's = 292, 275) of participants with MS were
      recruited from across the United States. Participants in both studies completed a
      questionnaire battery that included the MSSE and measures of symptoms,
      dysfunction, disability, psychosocial aspects, mental/emotional well-being, and
      quality of life. Factorial validity was tested using confirmatory factor analysis
      (CFA), whereas construct validity was examined based on bivariate correlations
      with scores from other measures. RESULTS: The two-factor measurement model
      provided a poor fit for the 18 items on the MSSE in both the samples. This model
      provided a good fit for a modified, 10-item scale in both samples. The 10-item
      version of the MSSE was highly correlated with the original MSSE (r = 0.97, p <
      0.001) and related constructs (e.g. disability, r = 0.69, p < 0.0001). The
      standardized Cronbach's alphas of the two subscales (function and control) of the
      10-item version ranged between 0.78 and 0.94 for both samples. CONCLUSIONS:
      Scores from the modified, 10-item version of the MSSE provide a valid and
      reliable measure of MS-specific self-efficacy among persons with MS. Implications
      for Rehabilitation The importance of self-efficacy in managing the consequences
      of multiple sclerosis (MS) has increased. The Multiple Sclerosis Self-Efficacy
      (MSSE) Scale was developed and validated for measuring self-efficacy in function
      maintenance and control over MS from patients' perspectives. In the past almost
      20 years, this scale has not undergone additional validation of its factor
      structure and construct validity in large-scale samples of persons with MS. The
      original two-factor construct did not provide a good fit for the 18 items on the
      MSSE in two independent samples. We modified the MSSE and found the 10 items
      fitted by the two-factor construct well with one sample and demonstrated cross
      validity of the 10 items in the second sample. The 10-item version of the MSSE
      has good reliability and construct validity in both independent samples.
      Researchers and clinicians should adopt these 10 items when examining MS self
      efficacy of patients.

PMID- 25749525
TI  - Transcriptome-wide identification and study of cancer-specific splicing events
      across multiple tumors.
AB  - Dysregulation of alternative splicing (AS) is one of the molecular hallmarks of
      cancer, with splicing alteration of numerous genes in cancer patients. However,
      studying splicing mis-regulation in cancer is complicated by the large noise
      generated from tissue-specific splicing. To obtain a global picture of cancer
      specific splicing, we analyzed transcriptome sequencing data from 1149 patients
      in The Cancer Genome Atlas project, producing a core set of AS events
      significantly altered across multiple cancer types. These cancer-specific AS
      events are highly conserved, are more likely to maintain protein reading frame,
      and mainly function in cell cycle, cell adhesion/migration, and insulin signaling
      pathways. Furthermore, these events can serve as new molecular biomarkers to
      distinguish cancer from normal tissues, to separate cancer subtypes, and to
      predict patient survival. We also found that most genes whose expression is
      closely associated with cancer-specific splicing are key regulators of the cell
      cycle. This study uncovers a common set of cancer-specific AS events altered
      across multiple cancers, providing mechanistic insight into how splicing is mis
      regulated in cancers. 

PMID- 25749527
TI  - Rotavirus VP6 protein expressed in cell culture by HSV-1-based vectors.

PMID- 25749528
TI  - Late sciatic nerve axonotmesis following acetabular reconstruction plate.
AB  - Sciatic nerve injuries associated with acetabular fractures can be post
      traumatic, perioperative or postoperative. Late postoperative injury is very
      uncommon and can be due to heterotopic ossifications, muscular scarring, or
      implant migration. A case is presented of a patient with a previous transverse
      acetabular fracture treated with a reconstruction plate for the posterior column.
      After 17 years, she presented with progressive pain and motor deficit in the
      sciatic territory. Radiological and neurophysiological assessments were performed
      and the patient underwent surgical decompression of the sciatic nerve. A
      transection of the nerve was observed that was due to extended compression of one
      of the screws. At 4 years postoperatively, her pain had substantially diminished
      and the paresthesias in her leg had resolved. However, her motor symptoms did not
      improve. This case report could be relevant due to this uncommon delayed sciatic
      nerve injury due to prolonged hardware impingement. 

PMID- 25749529
TI  - A real-time chirp-coded imaging system with tissue attenuation compensation.
AB  - In ultrasound imaging, pulse compression methods based on the transmission (TX)
      of long coded pulses and matched receive filtering can be used to improve the
      penetration depth while preserving the axial resolution (coded-imaging). The
      performance of most of these methods is affected by the frequency dependent
      attenuation of tissue, which causes mismatch of the receiver filter. This,
      together with the involved additional computational load, has probably so far
      limited the implementation of pulse compression methods in real-time imaging
      systems. In this paper, a real-time low-computational-cost coded-imaging system
      operating on the beamformed and demodulated data received by a linear array probe
      is presented. The system has been implemented by extending the firmware and the
      software of the ULA-OP research platform. In particular, pulse compression is
      performed by exploiting the computational resources of a single digital signal
      processor. Each image line is produced in less than 20 MUs, so that, e.g., 192
      line frames can be generated at up to 200 fps. Although the system may work with
      a large class of codes, this paper has been focused on the test of linear
      frequency modulated chirps. The new system has been used to experimentally
      investigate the effects of tissue attenuation so that the design of the receive
      compression filter can be accordingly guided. Tests made with different chirp
      signals confirm that, although the attainable compression gain in attenuating
      media is lower than the theoretical value expected for a given TX Time-Bandwidth
      product (BT), good SNR gains can be obtained. For example, by using a chirp
      signal having BT=19, a 13 dB compression gain has been measured. By adapting the
      frequency band of the receiver to the band of the received echo, the signal-to
      noise ratio and the penetration depth have been further increased, as shown by
      real-time tests conducted on phantoms and in vivo. In particular, a 2.7 dB SNR
      increase has been measured through a novel attenuation compensation scheme, which
      only requires to shift the demodulation frequency by 1 MHz. The proposed method
      characterizes for its simplicity and easy implementation.

PMID- 25749530
TI  - Advantages and Disadvantages of Transtibial, Anteromedial Portal, and Outside-In
      Femoral Tunnel Drilling in Single-Bundle Anterior Cruciate Ligament
      Reconstruction: A Systematic Review.
AB  - PURPOSE: Controversy exists regarding the best method for creating the knee
      anterior cruciate ligament (ACL) femoral tunnel or socket. The purpose of this
      study was to systematically review the risks, benefits, advantages, and
      disadvantages of the endoscopic transtibial (TT) technique, anteromedial portal
      technique, outside-in technique, and outside-in retrograde drilling technique for
      creating the ACL femoral tunnel. METHODS: A PubMed search of English-language
      studies published between January 1, 2000, and February 17, 2014, was performed
      using the following keywords: "anterior cruciate ligament" AND "femoral tunnel."
      Included were studies reporting risks, benefits, advantages, and/or disadvantages
      of any ACL femoral technique. In addition, references of included articles were
      reviewed to identify potential studies missed in the original search. RESULTS: A
      total of 27 articles were identified through the search. TT technique advantages
      include familiarity and proven long-term outcomes; disadvantages include the risk
      of nonanatomic placement because of constrained (TT) drilling. Anteromedial
      portal technique advantages include unconstrained anatomic placement;
      disadvantages include technical challenges, short tunnels or sockets, and
      posterior-wall blowout. Outside-in technique advantages include unconstrained
      anatomic placement; disadvantages include the need for 2 incisions. Retrograde
      drilling technique advantages include unconstrained anatomic placement, as well
      as all-epiphyseal drilling in skeletally immature patients; disadvantages include
      the need for fluoroscopy for all-epiphyseal drilling. CONCLUSIONS: There is no
      one, single, established "gold-standard" technique for creation of the ACL
      femoral socket. Four accepted techniques show diverse and subjective advantages,
      disadvantages, risks, and benefits. LEVEL OF EVIDENCE: Level V, systematic review
      of Level II through V evidence.

PMID- 25749531
TI  - Biochemical and Cellular Assessment of Acetabular Chondral Flaps Identified
      During Hip Arthroscopy.
AB  - PURPOSE: To analyze chondral flaps debrided during hip arthroscopy to determine
      their biochemical and cellular composition. METHODS: Thirty-one full-thickness
      acetabular chondral flaps were collected during hip arthroscopy. Biochemical
      analysis was undertaken in 21 flaps from 20 patients, and cellular viability was
      determined in 10 flaps from 10 patients. Biochemical analysis included
      concentrations of (1) DNA (an indicator of chondrocyte content), (2)
      hydroxyproline (an indicator of collagen content), and (3) glycosaminoglycan (an
      indicator of chondrocyte biosynthesis). Higher values for these parameters
      indicated more healthy tissue. The flaps were examined to determine the
      percentage of viable chondrocytes. RESULTS: The percentage of acetabular chondral
      flap specimens that had concentrations within 1 SD of the mean values reported in
      previous normal cartilage studies was 38% for DNA, 0% for glycosaminoglycan, and
      43% for hydroxyproline. The average cellular viability of our acetabular chondral
      flap specimens was 39% (SD, 14%). Only 2 of the 10 specimens had more than half
      the cells still viable. There was no correlation between (1) the gross
      examination of the joint or knowledge of the patient's demographic
      characteristics and symptoms and (2) biochemical properties and cell viability of
      the flap, with one exception: a degenerative appearance of the surrounding
      cartilage correlated with a higher hydroxyproline concentration. CONCLUSIONS:
      Although full-thickness acetabular chondral flaps can appear normal grossly, the
      biochemical properties and percentage of live chondrocytes in full-thickness
      chondral flaps encountered in hip arthroscopy show that this tissue is not
      normal. CLINICAL RELEVANCE: There has been recent interest in repairing chondral
      flaps encountered during hip arthroscopy. These data suggest that acetabular
      chondral flaps are not biochemically and cellularly normal. Although these flaps
      may still be valuable mechanically and/or as a scaffold in some conductive or
      inductive capacity, further study is required to assess the clinical benefit of
      repair.

PMID- 25749533
TI  - Promoting Health Literacy in an HIV-infected Population: Creating Staff
      Awareness.

PMID- 25749532
TI  - HIV-infected Women's Perspectives on the Use of the Internet for Social Support:
      A Potential Role for Online Group-based Interventions.
AB  - While the development and implementation of HIV-related online interventions has
      expanded, few have been tailored for women or have leveraged Web 2.0's
      capabilities to provide social support. We conducted semi-structured interviews
      with 27 women with HIV at an urban community health center to understand their
      perspectives on the potential role of the Internet and the use of an online group
      format to provide social support. Data were analyzed using the constant
      comparative method. We identified six themes: a need for groups and increased
      sense of connectedness, convenience and accessibility, trust as a precondition
      for participating, online groups as a potential facilitator or barrier to
      expression, limited digital access and literacy, and privacy concerns. Overall,
      women were highly supportive of online group-based interventions but acknowledged
      the need for increased digital access and Internet navigation training. Hybrid
      (in-person and online) interventions may be most useful for women with HIV. 

PMID- 25749535
TI  - [Oncology-related issues of angiotensin-receptor blockers].
AB  - Recently controversial data emerged regarding the cancer inducing activity of
      angiotensin-receptor blockers. There may be several reasons which may explain the
      controversial data published in the scientific literature including wrong trial
      design or misinterpretation of data. Considering the large number of patients
      receiving treatment for hypertension, it is essential to have a clear view of the
      cancer-related safety of these drugs. This paper tries to give an overview on
      this issue based on data available in the literature. According to our present
      knowledge, angiotensin-receptor blockers exert more likely anticancer activity
      rather than carcinogenesis inducing effect. In fact, some oncologic trials point
      to this direction, because angiotensin-receptor blockers are suggested as co
      treatment to chemotherapy in cases of pancreatic, oesophageal and gastric
      cancers.

PMID- 25749536
TI  - [Ocular symptoms and treatment of Ebola virus disease].
AB  - Ocular signs and symptoms of Ebola infection initially suggest banal
      conjunctivitis, but in advanced cases severe haemorrhagic conjunctivitis appears
      and, in the final stage of the disease, retinal and chorioidal haemorrhages may
      occur which can cause even blindness. Although the viral infection accompanied by
      ocular symptoms of a non-specific conjunctivitis, the high fever present from the
      onset of the disease should raise the suspicion of Ebola infection. There is no
      causal therapy know so far, and the only adjunctive treatment may be delivered by
      an ophthalmologist. Because the virus can be detected in the tear, it can
      theoretically be the mediator of the infection and, therefore, ophthalmological
      examinations should be carried out with the highest caution. In case of suspected
      Ebola infection the nearest competent healthcare authority should be immediately
      alerted in order to take further actions.

PMID- 25749534
TI  - Clinicopathologic characteristics and outcomes of renal thrombotic
      microangiopathy in anti-neutrophil cytoplasmic autoantibody-associated
      glomerulonephritis.
AB  - BACKGROUND AND OBJECTIVES: Thrombotic microangiopathy (TMA) in ANCA-associated
      vasculitis (AAV) has been mainly reported in isolated case reports. The aim of
      this study was to analyze clinical and pathologic characteristics and prognosis
      of patients with renal TMA in ANCA-associated GN in a large cohort of Chinese
      patients. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Clinical and renal
      histopathologic data of 220 patients with biopsy-proven ANCA-associated GN from
      1996 to 2013 were retrospectively analyzed. Patients were followed up for a
      median period of 32 (interquartile range [IQR], 12-65) months, and outcomes of
      patients were analyzed. RESULTS: Among the 220 patients with ANCA-associated GN,
      30 were identified having concomitant renal TMA by pathologic evaluation.
      Compared with the non-TMA group, patients with renal TMA presented with more
      severe renal injury, as evidenced clinically by a higher level of serum
      creatinine at diagnosis (5.0 [IQR, 3.5-9.0] versus 3.2 [IQR, 1.7-6.8] mg/dl;
      P=0.02) and pathologically by a higher percentage of cellular crescents (15.0%
      [IQR, 6.9%-34.9%] versus 6.9% [IQR, 0%-21.1%]; P=0.04) and more severe
      interstitial infiltration (2 [IQR, 2-2] versus 2 [IQR, 1-2]; P=0.03) in renal
      biopsies. Furthermore, multivariate analysis showed that renal TMA was
      independently associated with mortality of patients with AAV after adjusting for
      age, sex, initial serum creatinine, tubular atrophy, and interstitial fibrosis
      (hazard ratio, 1.92; 95% confidence interval, 1.08 to 3.41; P=0.03) or for age,
      sex, the histopathologic classification scheme proposed by Berden et al. (J Am
      Soc Nephrol 21: 1628-1636, 2010), tubular atrophy, and interstitial fibrosis
      (hazard ratio, 1.95; 95% confidence interval, 1.07 to 3.55; P=0.03). CONCLUSIONS:
      Renal TMA in ANCA-associated GN is not rare and presents with more severe renal
      injury. Renal TMA is independently associated with all-cause mortality in
      patients with AAV.

PMID- 25749537
TI  - [Cloning and law in Hungary].
AB  - Reproductive human cloning is prohibited in Hungary, as in many other countries.
      Therapeutic human cloning is not prohibited, just like in many other countries.
      Stem cell therapy is also allowed. Article III, paragraph (3) of the Hungarian
      basic law (constitution) strictly forbids total human cloning. Article 1 of the
      Additional Protocol to the Oviedo Convention, on the Prohibition of Cloning Human
      Beings (1998) stipulates that any intervention seeking to create a human being
      genetically identical to another human being, whether living or dead, is
      prohibited. In Hungary, according to Article 174 of the Criminal Code, total
      human cloning constitutes a crime. Article 180, paragraph (3) of the Hungarian
      Act on Health declares that embryos shall not be brought about for research
      purposes; research shall be conducted only on embryos brought about for
      reproductive purposes when this is authorized by the persons entitled to decide
      upon its disposal, or when the embryo is damaged. Article 180, paragraph (5) of
      the Hungarian Act on Health stipulates that multiple individuals who genetically
      conform to one another shall not be brought about. According to Article 181,
      paragraph (1) of the Hungarian Act on Health, an embryo used for research shall
      be kept alive for not longer than 14 days, not counting the time it was frozen
      for storage and the time period of research.

PMID- 25749538
TI  - [The relationship of work-related psychosocial risk factors with depressive
      symptoms among Hungarian workers: preliminary results of the Hungarian Work
      Stress Survey].
AB  - INTRODUCTION: Research has shown that psychosocial stress acts as a risk factor
      for mental disorders. AIM: The present study aims at processing the preliminary
      results of the Hungarian Survey of Work Stress, concerning the relationship
      between depressive symptoms and work stress. METHODS: Cross-sectional survey
      among Hungarian workers was carried out (n = 1058, 27.5% man, 72.5% woman, age
      37.2 years, SD = 11 years). Psychosocial factors were measured using the COPSOQ
      II questionnaire, while BDI-9 was used for the assessment of depressive symptoms.
      Statistical analysis was carried out applying Spearman's correlation and logistic
      regression. RESULTS: A quarter of the workers reported moderate or severe
      symptoms of depression (BDI>=19). The study confirmed the association between
      depressive symptoms and work-family conflict (OR = 2.21, CI: 1.82-2.68),
      possibilities for development (OR = 0.76, CI: 0.59-0.97) meaning of work (OR =
      0.69, CI: 0.59-0.89) and commitment (OR = 0.60, CI: 0.47-0.78). CONCLUSION: The
      results point toward the need of such organizational measures that allow for the
      reduction of psychosocial stress.

PMID- 25749539
TI  - [Autoimmune haemolytic anaemia: a review and report of four cases].
AB  - Treatment of autoimmune haemolytic anaemia is still a challenge to clinicians.
      Even today it may be lethal. Half of the cases are secondary due to an underlying
      disease, and the others are primary or idiopathic cases. According to the
      specificity and type of autoantibodies there are warm and cold type forms of
      autoimmune haemolytic anaemia. The hallmark of the diagnosis is to detect the
      presence of haemolysis by clinical and laboratory signs and detect the underlying
      autoantibodies. Treatment of autoimmune haemolytic anaemia is still a challenge
      to clinicians. We still loose patients due to excessive haemolysis or severe
      infections caused by immunosuppression. First line treatment is corticosteroids.
      Other immunosuppressive agents like: cyclophosphamide, azathioprine, cyclosporine
      or the off label rituximab can be used in case of corticosteroid refractoriness.
      Splenectomy is a considerable option in selective cases. The authors discuss
      treatment options and highlight difficulties by presenting 4 cases.

PMID- 25749540
TI  - [Jozsef Honti Dr. (1938-2014)].

PMID- 25749542
TI  - Sudden sensorineural hearing loss: Is antiviral treatment really necessary?
AB  - OBJECTIVES: It was aimed to investigate the necessity of antiviral agents in the
      ISSHL treatment. METHODS: In this study, the patients, diagnosed with sudden
      hearing loss and admitted in the first 7 days of hearing loss were divided into
      two groups; a combination therapy was administered to one of the groups, and
      famciclovir was administered to the other group as an antiviral treatment in
      addition to the combined therapy. Both groups were compared in terms of levels of
      recovery. RESULTS: No statistically significant difference was found in the
      recovery rates between the two groups (p=0.7). CONCLUSION: In this study, the
      additional antiviral treatment was found to have no effect on the remission rates
      in patients with ISSHL treated with combined therapy.

PMID- 25749543
TI  - An objective analysis of sebum, pH and moisture levels of the external ear canal
      skin.
AB  - OBJECTIVE: To determine sebum, pH and moisture levels of external ear canal skin,
      and compare the patients who complain of ear itching and the normal population
      for these parameters. And evaluate the improvement subjectively in the ones given
      dexamethasone sodium phosphate (DSP) cream or placebo-water in oil emulsion type
      cream, and to determine the changes in sebum, pH and moisture levels after the
      treatment. METHODS: 32 females with the complaint of isolated external ear canal
      itching and 42 healthy women were included in this randomized prospective
      controlled study. The sebum, pH and moisture levels of ear skin of the patients
      and the controls were determined from baseline and following treatment. Patients
      used DSP in their right and the placebo in their left ears for 15 days.
      Subjective analysis of itching level was measured at baseline, and on 15th and
      30th days using visual analog scale (VAS). RESULTS: There was no statistically
      significant difference between pretreatment and post-treatment pH and sebum
      levels of the study group and the control group. However, pretreatment and post
      treatment moisture levels of the study group were significantly higher (p<0.001).
      CONCLUSION: The study found an association of increased moisture levels of the
      external ear canal skin and isolated ear itching.

PMID- 25749544
TI  - Case presentation of an intranasal ectopic tooth in a pediatric patient.
AB  - An ectopic tooth in the nasal cavity is a rare phenomenon, especially on the
      inferior turbinate. In most of the reported cases, no etiological explanation of
      the intranasal teeth has been suggested or found. In children, intranasal ectopic
      teeth are usually associated with cleft lip and alveolus. Here, we report a rare
      case of a pediatric patient with unilateral nasal obstruction due to an
      intranasal ectopic tooth originating from the inferior turbinate without any
      facial and dental deformities. This case is unique due to the unusual location of
      the ectopic tooth and its presentation in a child without facial and dental
      deformities. 

PMID- 25749545
TI  - Understanding the ionic liquid [NC4111][NTf2] from individual building blocks: an
      IR-spectroscopic study.
AB  - This study explores the interactions underlying the IR spectra of the ionic
      liquid [NC4111][NTf2] and its deuterated isotopomer [d9-NC4111][NTf2] by first
      isolating the spectra of charged ionic building blocks using mass-selective CIVP
      spectroscopy and then following the evolution of these bands upon sequential
      assembly of the ionic constituents. The spectra of the (1,1) and (2,2) neutral
      ion pairs are recorded using superfluid helium droplets as well as a solid neon
      matrix, while those of the larger charged aggregates are again obtained with
      CIVP. In general, the cluster spectra are similar to that of the bulk, with the
      (2,2) system displaying the closest resemblance. Analysis of the polarization
      dependent band intensities of the neutral ion pairs in liquid droplets as a
      function of external electric field yields dipole moments of the neutral
      aggregates. This information allows a coarse assessment of the packing structure
      of the neutral pairs to be antiparallel at 0.37 K, in contrast to the parallel
      arrangement found for the assembly of small, high-dipole neutral molecules with
      large rotational constants (e.g., HCN). The role of an extra anion or cation
      attached to both the (1,1) and the (2,2) ion pairs to form the charged clusters
      is discussed in the context of an additional remote, more unfavorable binding
      site intrinsic to the nature of the charged IL clusters and as such not
      anticipated in the bulk phase. Whereas for the anion itself only the lowest
      energy trans conformer was observed, the higher clusters showed an additional
      population of the cis conformer. The interactions are found to be consistent with
      a minimal role of hydrogen bonding. 

PMID- 25749546
TI  - The etiology of low-grade gliomas: pathological and clinical considerations about
      radiation-induced low-grade gliomas.
AB  - The only environmental factor undoubtedly linked to an increased risk of brain
      tumors (including gliomas) is therapeutic X-rays. We aim to conduct a detailed
      study of radiation-induced low-grade gliomas, in order to better understand the
      pathogenesis of such gliomas. Furthermore, we want do prove whether or not there
      are significant differences, according to clinical features and biological
      behavior, between this type of tumor and general low-grade gliomas. We analyzed
      the existent literature of low-grade radiation-induced glioma case reports and
      other epidemiological reports based on the experience of the senior author. We
      were able to collect 20 cases of such gliomas. Demographic data and previous X
      ray details, along with latency intervals of all patients are provided. The
      amount of radiation able to cause mutations is not necessarily very high, as
      tumors occur even after low doses of radiation (as 3-5 GY). The incidence of this
      kind of tumors may be underestimated and may rise in the future. Care must be
      taken when observing patients who were irradiated more than 10 years before,
      especially in the recent years in which access to radiosurgical and radiation
      therapies has increased in the general population for treating many cerebral
      pathologies. Radiation-induced low-grade gliomas appear to be different from
      general gliomas only in terms of age in which they occur. In terms of clinical
      and biological behavior, there seem to be no differences, even though exceptional
      cases are reported.

PMID- 25749547
TI  - Role of monovalent and divalent metal cations in human ribokinase catalysis and
      regulation.
AB  - Human ribokinase (RK) is a member of the ribokinase family, and is the first
      enzyme responsible for D-ribose metabolism, since D-ribose must first be
      converted into D-ribose-5-phosphate to be further metabolized and incorporated
      into ATP or other high energy phosphorylated compounds. Despite its biological
      importance, RK is poorly characterized in eukaryotes and especially in human. We
      have conducted a comprehensive study involving catalytic and regulatory features
      of the human enzyme, focusing on divalent and monovalent metal regulatory
      effects. Mg(2+), Mn(2+), and Co(2+) support enzyme activity although at different
      rates, with Mn(2+) being the most effective. Analysis of the divalent cation
      requirement in the wild type enzyme demonstrates that in addition to that
      chelated by the nucleotide substrate, an activating cation (either Mn(2+) or
      Mg(2+)) is required to obtain full activity of the enzyme, with the affinity for
      both divalent cations being almost the same (4 and 8 uM respectively). Besides
      metal cation activation, inhibition of the enzyme activity by increasing
      concentrations of Mn(2+) but not Mg(2+) is observed. Also the role of residues
      N199 and E202 of the highly conserved NXXE motif present at the active site has
      been evaluated regarding Mg(2+) and phosphate binding. K(+) (but not Na(+)) and
      PO4 (3-) activate the wild type enzyme, whereas the N199L and E202L mutants
      display a dramatic decrease in kcat and require higher free Mg(2+) concentrations
      than the wild type enzyme to reach maximal activity, and the activating effect of
      PO4 (3-) is lost. The results demonstrated a complex regulation of the human
      ribokinase activity where residues Asn199 and Glu202 play an important role.

PMID- 25749548
TI  - Estimating development cost of an interactive website based cancer screening
      promotion program.
AB  - OBJECTIVES: The aim of this study was to estimate the initial development costs
      for an innovative talk show format tailored intervention delivered via the
      interactive web, for increasing cancer screening in women 50-75 who were non
      adherent to screening guidelines for colorectal cancer and/or breast cancer.
      METHODS: The cost of the intervention development was estimated from a societal
      perspective. Micro costing methods plus vendor contract costs were used to
      estimate cost. Staff logs were used to track personnel time. Non-personnel costs
      include all additional resources used to produce the intervention. RESULTS:
      Development cost of the interactive web based intervention was $.39 million, of
      which 77% was direct cost. About 98% of the cost was incurred in personnel time
      cost, contract cost and overhead cost. CONCLUSIONS: The new web-based disease
      prevention medium required substantial investment in health promotion and media
      specialist time. The development cost was primarily driven by the high level of
      human capital required. The cost of intervention development is important
      information for assessing and planning future public and private investments in
      web-based health promotion interventions.

PMID- 25749549
TI  - Achieving large linear elasticity and high strength in bulk nanocompsite via
      synergistic effect.
AB  - Elastic strain in bulk metallic materials is usually limited to only a fraction
      of 1%. Developing bulk metallic materials showing large linear elasticity and
      high strength has proven to be difficult. Here, based on the synergistic effect
      between nanowires and orientated martensite NiTi shape memory alloy, we developed
      an in-situ Nb nanowires -orientated martensitic NiTi matrix composite showing an
      ultra-large linear elastic strain of 4% and an ultrahigh yield strength of 1.8
      GPa. This material also has a high mechanical energy storage efficiency of 96%
      and a high energy storage density of 36 J/cm(3) that is almost one order of
      larger than that of spring steel. It is demonstrated that the synergistic effect
      allows the exceptional mechanical properties of nanowires to be harvested at
      macro scale and the mechanical properties of matrix to be greatly improved,
      resulting in these superior properties. This study provides new avenues for
      developing advanced composites with superior properties by using effective
      synergistic effect between components. 

PMID- 25749550
TI  - Factors influencing the provision of adherence support by community pharmacists:
      A structural equation modeling approach.
AB  - BACKGROUND: Non-adherence to medication represents an important barrier to
      achieving optimum patient outcomes. Community pharmacists are well placed to
      deliver interventions to support adherence. AIMS: To investigate community
      pharmacists' activities in supporting patient adherence; and identify factors
      influencing pharmacists' provision of adherence support. METHOD: A random sample
      of 2020 Australian community pharmacies was mailed a questionnaire investigating
      their provision of adherence support. The self-completed, structured
      questionnaire consisted of eight sections, five of which were relevant to this
      study: strategies used to identify non-adherent patients, strategies used to
      support patients' adherence to medications, pharmacists' attitudes toward
      provision of adherence support, perceived barriers to provision of adherence
      support, and demographics. Structural equation modeling (SEM) was used to
      determine potential influencing factors. RESULTS: A response rate of 31% was
      achieved (n = 627). Pharmacists reported using strategies to identify non
      adherent patients for less than half (45%) of the prescriptions dispensed. A mean
      of 8.4 +/- 14.9 (mean +/- SD) strategies was used by respondents in the 7 days
      prior to survey completion. Dose administration aids was the most commonly used
      strategy (provided by 96.5% of respondents). Time pressure for patients (68%) was
      perceived by pharmacists as the main barrier to adherence support. SEM identified
      "stakeholders/skills" and "number of full time equivalent staff" as influencing
      provision of adherence support strategies. CONCLUSION: Provision of adherence
      support by pharmacists was episodic and infrequent, impeded by a number of
      barriers. By addressing barriers, it is possible to enable pharmacists to become
      more proactive and effective in supporting patient adherence.

PMID- 25749551
TI  - MEG analysis of neural dynamics in attention-deficit/hyperactivity disorder with
      fuzzy entropy.
AB  - The aim of this study was to analyze the neural dynamics in attention
      deficit/hyperactivity disorder (ADHD). For this purpose, magnetoencephalographic
      (MEG) background activity was analyzed using fuzzy entropy (FuzzyEn), an entropy
      measure that quantifies signal irregularity, in 13 ADHD patients and 14 control
      children. Additionally, relative power (RP) was computed in conventional
      frequency bands (delta, theta, alpha, beta and gamma). FuzzyEn results showed
      that MEG activity was more regular in ADHD patients than in controls. Moreover,
      we found an increase of power in delta band and a decrease in the remaining
      frequency bands. Statistically significant differences (p-values <0.05;
      nonparametric permutation test for multiple comparisons) were detected for
      FuzzyEn in the posterior and left temporal regions, and for RP in the posterior,
      anterior and left temporal regions. Our results support the hypothesis that ADHD
      involves widespread functional brain abnormalities, affecting more areas than
      fronto-striatal circuits, such as the left temporal and posterior regions. 

PMID- 25749552
TI  - Instrumenting gait with an accelerometer: a system and algorithm examination.
AB  - Gait is an important clinical assessment tool since changes in gait may reflect
      changes in general health. Measurement of gait is a complex process which has
      been restricted to the laboratory until relatively recently. The application of
      an inexpensive body worn sensor with appropriate gait algorithms (BWM) is an
      attractive alternative and offers the potential to assess gait in any setting. In
      this study we investigated the use of a low-cost BWM, compared to laboratory
      reference using a robust testing protocol in both younger and older adults. We
      observed that the BWM is a valid tool for estimating total step count and mean
      spatio-temporal gait characteristics however agreement for variability and
      asymmetry results was poor. We conducted a detailed investigation to explain the
      poor agreement between systems and determined it was due to inherent differences
      between the systems rather than inability of the sensor to measure the gait
      characteristics. The results highlight caution in the choice of reference system
      for validation studies. The BWM used in this study has the potential to gather
      longitudinal (real-world) spatio-temporal gait data that could be readily used in
      large lifestyle-based intervention studies, but further refinement of the
      algorithm(s) is required. 

PMID- 25749553
TI  - Generation of tidal volume via gentle chest pressure in children over one year
      old.
AB  - BACKGROUND: In the event of cardiac arrest, cardiopulmonary resuscitation (CPR)
      is a well-established technique to maintain oxygenation of tissues and organs
      until medical equipment and staff are available. During CPR, chest compressions
      help circulate blood and have been shown in animal models to be a means of short
      term oxygenation. In this study, we tested whether gentle chest pressure can
      generate meaningful tidal volume in paediatric subjects. METHODS: This
      prospective cohort pilot study recruited children under the age of 17 years and
      undergoing any surgery requiring general anaesthetic and endotracheal intubation.
      After induction of general anaesthesia, tidal volumes were obtained before and
      after intubation by applying a downward force on the chest which was not greater
      than the patient's weight. Mean tidal volumes were compared for unprotected
      versus protected airway and for type of surgery. RESULTS: Mean tidal volume
      generated with an unprotected and protected airway was 2.7 (1.7) and 2.9 (2.3)
      mL/kg, respectively. Mean tidal volume generated with mechanical ventilation was
      13.6 (4.9) mL/kg. No statistical significance was found when comparing tidal
      volumes generated with an unprotected or protected airway (p = 0.20), type of
      surgery (tonsillectomy and/or adenoidectomy versus other surgery) (unprotected, p
      = 0.09; protected, p = 0.37), and when age difference between groups was taken
      into account (p = 0.34). CONCLUSIONS: Using gentle chest pressure, we were able
      to generate over 20% of the tidal volume achieved with mechanical ventilation.
      Our results suggest that gentle chest pressure may be a means to support
      temporary airflow in children.

PMID- 25749555
TI  - Parsing susceptibility and severity dimensions of health risk perceptions.
AB  - Risk perceptions, an important determinant of positive behavioral change, are
      often conceptualized as an additive or multiplicative index of two concepts:
      susceptibility to and severity of a health risk. Susceptibility is the
      possibility of experiencing a health risk, whereas severity is its seriousness or
      harmfulness. This article challenged the current theorization of risk
      perceptions. To demonstrate the differential perceptions of susceptibility and
      severity, two self-report studies (N = 70, each) and one reaction time study (N =
      476) provided data on 50 health conditions that varied on several risk
      characteristics (e.g., prevalence, personal experience). Results showed that
      susceptibility and severity were two distinct, inversely related concepts.
      Perceived susceptibility and severity varied by risk characteristics, mainly
      prevalence (i.e., how common a health risk was perceived to be). Self-report data
      showed that a progressive increase in perceptions of a health risk prevalence
      rates was associated with an increase in susceptibility and a decrease in
      severity (and vice versa). Reaction-time data mirrored this pattern and showed
      these differential perceptions of susceptibility and severity were highly
      accessible, as evident by fast reaction times. Several individual differences
      (e.g., optimism) emerged as significant predictors of risk perceptions and their
      accessibility. Theoretical and practical implications are discussed. 

PMID- 25749556
TI  - [Intrathyroid parathyroid adenoma in a patient with chronic lithium treatment].

PMID- 25749557
TI  - Upcoming biomarkers for the diagnosis of Kawasaki disease: A review.
AB  - Kawasaki disease (KD) is a major cause of acquired heart disease among children
      and increases the risk of myocardial infarction. While the biochemical basis of
      the disease is unclear, the evidence suggests interplay between a microbial
      infection and a genetic predisposition in the development of the disease.
      Diagnosis of KD based on clinical observation is not completely reliable and is
      problematic due to the time-sensitive nature of the disease. Hence,
      identification of inflammatory, proteomic, and genetic biomarkers may assist in
      earlier and more effective diagnosis and treatment. This review of observational
      studies and clinical trials analyzes biomarkers in recent research that may be
      used to establish a gold standard test for KD diagnosis. 65 articles in the
      literature are assessed to investigate these new biomarkers in addition to
      biomarkers presently in use. ESR>=40mm/h, leukocyte count >=16*10(9)/L and
      increased WBC count are together suggestive of the presence of KD. Among
      proteomic biomarkers, elevated NT-proBNP and differing levels of several other
      proteomic biomarkers such as iNOS in monocytes and neutrophils have been observed
      in KD patients. Genetic polymorphisms of six HLA class I genes have also been
      linked with the disease, alongside MICA alleles A4 and A5.1. The results suggest
      that NT-proBNP is currently a very promising biomarker for future investigation;
      further research is warranted to allow for accurate and early detection of the
      disease using this biomarker. 

PMID- 25749558
TI  - Physical activity in relation to body size and composition in women in UK
      Biobank.
AB  - PURPOSE: Physical activity is thought to protect against obesity, but the
      evidence is limited and few large studies of this topic have direct, objective
      measures of several different anthropometric variables. We examined the
      association of self-reported physical activity with measures of total and central
      adiposity. METHODS: Our cross-sectional study included 38,201 premenopausal and
      94,592 postmenopausal healthy women aged 40 to 70 years in UK Biobank, recruited
      from 2006 to 2010. RESULTS: Means for total and vigorous physical activity were
      31.3 (SD, 30.8) and 9.7 (SD, 14.8) metabolic equivalent h/wk, respectively, for
      premenopausal and 34.4 (SD, 33.1) and 8.9 (SD, 15.6) metabolic equivalent h/wk,
      respectively, for postmenopausal women. Multiple linear regression models showed
      that in both premenopausal and postmenopausal women, body mass index, body fat
      mass and percentage, trunk fat mass and percentage, waist and hip circumference,
      and waist-to-hip ratio were lower in women with higher physical activity (P <
      .0001). Within each category of total physical activity, a larger proportion of
      vigorous physical activity was associated with lower adiposity (P < .0001).
      CONCLUSIONS: These findings support the roles of a physically active lifestyle
      and vigorous exercise in maintaining healthy body size and composition. Higher
      exercise intensity may be associated with lower adiposity, beyond the influence
      of exercise frequency and duration.

PMID- 25749560
TI  - The impact of the CB2-63 polymorphism on the histological presentation of chronic
      hepatitis B.
AB  - The impact of the cannabinoid receptor 2 (CB2) rs35761398 polymorphism on chronic
      hepatitis B (CHB) was evaluated in 106 consecutive biopsy-proven CHB patients
      naive for antiviral therapy. A histological activity index (HAI) > 8 (Ishak
      scoring) was more frequent in patients with CB2-63 RR than in those with CB2-63
      QR or QQ (37% vs. 16.7%, p < 0.05). The logistic regression analysis identified
      CB2-63 RR (p < 0.05) and a fibrosis score >3 (p < 0.005) as independently
      associated with an HAI >8. The observation that the CB2-63 RR variant is an
      independent predictor of extensive necroinflammation opens up new prospects in
      the study of CHB.

PMID- 25749559
TI  - What matters most: quantifying an epidemiology of consequence.
AB  - Risk factor epidemiology has contributed to substantial public health success. In
      this essay, we argue, however, that the focus on risk factor epidemiology has led
      epidemiology to ever increasing focus on the estimation of precise causal effects
      of exposures on an outcome at the expense of engagement with the broader causal
      architecture that produces population health. To conduct an epidemiology of
      consequence, a systematic effort is needed to engage our science in a critical
      reflection both about how well and under what conditions or assumptions we can
      assess causal effects and also on what will truly matter most for changing
      population health. Such an approach changes the priorities and values of the
      discipline and requires reorientation of how we structure the questions we ask
      and the methods we use, as well as how we teach epidemiology to our emerging
      scholars.

PMID- 25749562
TI  - The burden of chikungunya in the Pacific.

PMID- 25749561
TI  - Epidemiology of invasive fungal diseases among patients with haematological
      disorders in the Asia-Pacific: a prospective observational study.
AB  - We conducted a 2-year multicentre prospective observational study to determine
      the epidemiology of and mortality associated with invasive fungal diseases (IFDs)
      among patients with haematological disorders in Asia. Eleven institutions from 8
      countries/regions participated, with 412 subjects (28.2% possible, 38.3% probable
      and 33.5% proven IFDs) recruited. The epidemiology of IFDs in participating
      institutions was similar to Western centres, with Aspergillus spp. (65.9%) or
      Candida spp. (26.7%) causing the majority of probable and proven IFDs. The
      overall 30-day mortality was 22.1%. Progressive haematological disorder (odds
      ratio [OR] 5.192), invasive candidiasis (OR 3.679), and chronic renal disease (OR
      6.677) were independently associated with mortality. 

PMID- 25749554
TI  - Brain and kidney, victims of atrial microembolism in elderly hospitalized
      patients? Data from the REPOSI study.
AB  - BACKGROUND: It is well known that atrial fibrillation (AF) and chronic kidney
      disease (CKD) are associated with a higher risk of stroke, and new evidence links
      AF to cognitive impairment, independently from an overt stroke (CI). Our aim was
      to investigate, assuming an underlying role of atrial microembolism, the impact
      of CI and CKD in elderly hospitalized patients with AF. METHODS: We
      retrospectively analyzed the data collected on elderly patients in 66 Italian
      hospitals, in the frame of the REPOSI project. We analyzed the clinical
      characteristics of patients with AF and different degrees of CI. Multivariate
      logistic analysis was used to explore the relationship between variables and
      mortality. RESULTS: Among the 1384 patients enrolled, 321 had AF. Patients with
      AF were older, had worse CI and disability and higher rates of stroke,
      hypertension, heart failure, and CKD, and less than 50% were on anticoagulant
      therapy. Among patients with AF, those with worse CI and those with lower
      estimated glomerular filtration rate (eGFR) had a higher mortality risk (odds
      ratio 1.13, p=0.006). Higher disability levels, older age, higher systolic blood
      pressure, and higher eGFR were related to lower probability of oral anticoagulant
      prescription. Lower mortality rates were found in patients on oral anticoagulant
      therapy. CONCLUSIONS: Elderly hospitalized patients with AF are more likely
      affected by CI and CKD, two conditions that expose them to a higher mortality
      risk. Oral anticoagulant therapy, still underused and not optimally enforced, may
      afford protection from thromboembolic episodes that probably concur to the high
      mortality.

PMID- 25749563
TI  - Prevalence of phylogroups and O25/ST131 in susceptible and extended-spectrum beta
      lactamase-producing Escherichia coli isolates, the Netherlands.
AB  - To assess the distribution of phylogroups and O25/ST131 in the Netherlands, we
      performed a real-time polymerase chain reaction (PCR) on a collection of 108 wild
      type Escherichia coli (WT-EC) and 134 extended-spectrum beta-lactamase-producing
      E. coli (ESBL-EC). Phylogroup B2 was predominant, but ESBL-EC were less likely to
      belong to this phylogroup (48.5%) than were WT-EC (66.7%; p = 0.005). In WT-EC,
      phylogroups B2 and D seem to be more virulent, having a higher prevalence among
      midstream urine isolates and blood culture isolates, than in catheter-related
      urine isolates (83.3% and 87.9% vs. 61.9%; p 0.048). O25/ST131 is associated with
      ESBL production, being almost absent among phylogroup B2 WT-EC (61.5% vs. 5.6%; p
      < 0.001).

PMID- 25749564
TI  - Cytotoxic and genotoxic characterization of aluminum and silicon oxide
      nanoparticles in macrophages.
AB  - OBJECTIVE: Although aluminum oxide and silicon oxide nanoparticles are currently
      available as dental materials, there is a lack of basic information concerning
      their biocompatibility. This study evaluates the biological responses of cultured
      macrophages (RAW264) to aluminum oxide (Al2O3NPs) and silicon oxide nanoparticles
      (SiO2NPs) by analyzing cytotoxicity and genotoxicity. METHODS: The nanoparticles
      are amorphous and spherical, with diameters of 13 nm for the Al2O3NPs and 12 nm
      for the SiO2NPs. The cultured RAW264 are exposed to the nanoparticles (NPs) and
      examined for cytotoxicity using the WST-8 cell viability and Hoechst/PI apoptosis
      assay, for genotoxicity by micronucleus analysis, for changes in nuclear shape
      (deformed nuclei) and for comet assay using confocal microscopy, and
      micromorphological analysis is done using scanning and transmission electron
      microscopes. RESULTS: Nuclei and DNA damage because of exposure to both types of
      NPs is observed by inmunostaining genotoxicity testing. The cytotoxicity and
      genotoxicity are well correlated in this study. Numerous NPs are observed as
      large aggregates in vesicles, but less or nonexistent NP internalization is seen
      in the nucleus or cytoplasm. These morphological results suggest that a primary
      cause of cell disruption is the chemical changes of the NPs in the low pH of
      vesicles (i.e., ionization of Al2O3 or SiO2) for both types of oxide NPs.
      SIGNIFICANCE: Although further research on the elution of NP concentrations on
      cell or tissue activity under simulated clinical conditions is required, NP
      concentrations over 200 MUg/mL are large enough to induce cytotoxic and genotoxic
      effects to cells.

PMID- 25749565
TI  - The Ferritin-Heavy-Polypeptide-Like-17 (FTHL17) gene encodes a ferritin with low
      stability and no ferroxidase activity and with a partial nuclear localization.
AB  - BACKGROUND: Three functional ferritin genes have been identified so far in
      mammals, and they encode the cytosolic Heavy (FTH) and Light chain (FTL) and the
      mitochondrial ferritin. The expression of a transcript by a fourth ferritin-like
      gene (Ferritin-Heavy-Polypeptide-Like-17, FTHL17) on the X chromosome was
      reported in mouse spermatogonia and in early embryonic cells. METHODS: The
      intronless human FTHL17 gene encodes a protein with 64% identity to human FTH
      with substitution of key residues of the ferroxidase center. The gene was cloned
      into vectors for expression in Escherichia coli and mammalian cells, linked to a
      flag-tag. RESULTS: The recombinant FTHL17 from E. coli purified as an assembled
      24-mer ferritin devoid of ferroxidase activity and with a reduced physical
      stability. When transiently expressed in mammalian cells the flag-FTHL17
      assembled in ferritin shells that showed reduced stability to denaturants
      compared with flag H and L ferritins. Immunocytochemistry with anti-flag antibody
      decorated the nuclei of flag-FTHL17 transfected COS cells, but not those of the
      cells transfected with flag-FTH or flag-FTL. CONCLUSIONS: We concluded that
      FTHL17 encodes a ferritin-like protein without ferroxidase activity. Its
      restricted embryonic expression and partial nuclear localization suggest that
      this novel ferritin type may have functions other than iron storage. GENERAL
      SIGNIFICANCE: The work confirms the presence of a fourth functional human
      ferritin gene with properties distinct from the canonical cytosolic ones.

PMID- 25749567
TI  - Characterisation and comparison of temporal release profiles of nitric oxide
      generating donors.
AB  - BACKGROUND: Nitric oxide (NO) is a vital signalling molecule in a variety of
      tissues including the neuronal, vascular and reproductive system. However, its
      high diffusibility and inactivation make characterisation of nitrergic signalling
      difficult. The use of NO donors is essential to characterise downstream
      signalling pathways but knowledge of donor release capacities is lacking, thus
      making comparisons of donor responses difficult. NEW METHOD: This study
      characterises NO profiles of commonly used NO donors. Donors were stored under
      defined conditions and temporal release profiles detected to allow determination
      of released NO concentrations. RESULTS: Using NO-sensitive microsensors we
      assessed release profiles of NO donors following different storage times and
      conditions. We found that donors such as NOC-5 and PAPA-NONOate decayed
      substantially within days, whereas SNP and GSNO showed greater stability
      releasing consistent levels of NO over days. In all donors tested, the amount of
      released NO differs between frozen and unfrozen stocks. COMPARISON WITH EXISTING
      METHOD(S): Fluorescent and amperometric approaches to measure NO concentrations
      yield a wide range of levels. However, due to a lack of characterisation of the
      release profiles, inconsistent effects on NO signalling have been widely
      documented. Our systematic assessment of release profiles of a range of NO donors
      therefore provides new essential data allowing for improved and defined
      investigations of nitrergic signalling. CONCLUSIONS: This is the first systematic
      comparison of temporal release profiles of different NO donors allowing
      researchers to compare conditions across different studies and the use of defined
      NO levels by choosing specific donors and concentrations.

PMID- 25749568
TI  - Estimating the sample size required to detect an arterial spin labelling magnetic
      resonance imaging perfusion abnormality in voxel-wise group analyses.
AB  - BACKGROUND: Voxel-based analyses are pervasive across the range of neuroimaging
      techniques. In the case of perfusion imaging using arterial spin labelling (ASL),
      a low signal-to-noise technique, there is a tradeoff between the contrast-to
      noise required to detect a perfusion abnormality and its spatial localisation. In
      exploratory studies, the use of an a priori region of interest (ROI), which has
      the benefit of averaging multiple voxels, may not be justified. Thus the question
      considered in this study pertains to the sample size that is required to detect a
      voxel-level perfusion difference between groups and two algorithms are
      considered. NEW METHOD: Empirical 3T ASL data were acquired from 25 older adults
      and simulations were performed based on the group template cerebral blood flow
      (CBF) images. General linear model (GLM) and permutation-based algorithms were
      tested for their ability to detect a predefined hypoperfused ROI. Simulation
      parameters included: inter and intra-subject variability, degree of hypoperfusion
      and sample size. The true positive rate was used as a measure of sensitivity.
      RESULTS: For a modest group perfusion difference, i.e., 10%, 37 participants per
      group were required when using the permutation-based algorithm, whereas 20
      participants were required for the GLM-based algorithm. COMPARISON WITH EXISTING
      METHODS: This study advances the perfusion power calculation literature by
      considering a voxel-wise analysis with correction for multiple comparison.
      CONCLUSIONS: The sample size requirement to detect group differences decreased
      exponentially in proportion to increased degree of hypoperfusion. In addition,
      sensitivity to detect a perfusion abnormality was influenced by the choice of
      algorithm.

PMID- 25749569
TI  - Wnt1 Participates in Inflammation Induced by Lipopolysaccharide Through
      Upregulating Scavenger Receptor A and NF-kB.
AB  - The study investigated the role of wnt1 in the inflammatory response initiated by
      lipolysaccharide (LPS), and analyzed the association between wnt1, NF-KB, and
      inflammatory factors. THP-1 cells were activated with phorbol-12-myristate-13
      acetate (PMA) and treated with LPS to induce inflammation. THP-1 cells were
      transfected with wnt1siRNA and overexpression plasmid to explore the relationship
      among wnt1, SRA, and NF-KB. Inhibitor of beta-catenin and siRNA of FZD1were used
      to investigate the signaling events involved in SRA activation induced by wnt1.
      Levels of NF-kB protein and inflammatory cytokines were assessed followingwnt1
      siRNA and LPS treatment. PMA activation and LPS treatment of THP-1 cells
      increased wnt1 protein levels. Wnt1 promoted SRA expression through activation of
      canonical wnt pathway. Wnt1 increased NF-kB protein levels and enhanced the
      secretion of IL-6, TNF-alpha, and iNOS through binding to SRA. These findings
      suggest that wnt1 increased SRA and NF-kB protein levels and participated in the
      inflammatory response. 

PMID- 25749570
TI  - Postsurgical Acute Phase Reaction is Associated with Decreased Levels of
      Circulating Myostatin.
AB  - Muscle strength is of importance for postsurgical rehabilitation. Myostatin is a
      growth factor that regulates the size of muscles and could thus influence muscle
      mass and function in the postsurgical period. The aim of the present study was to
      study the changes in myostatin levels during the postsurgical inflammatory
      period. Myostatin was analysed in serum samples from two elective surgery groups,
      orthopaedic surgery (n = 24) and coronary bypass patients (n = 21). The samples
      were collected prior to surgery and 4 and 30 days after surgery. In the
      orthopaedic group, the median myostatin levels decreased from 3582 ng/L prior to
      surgery to 774 ng/L at day 4 (p < 0.001) and to 2016 ng/L at day 30 (p < 0.001).
      Median CRP increased from 2.35 mg/L preoperatively to 117 mg/L at day 4 and
      decreased to 5.5 mg/L at day 30 in the same group. The coronary bypass group
      showed a similar pattern with a decrease in myostatin from 4212 ng/L to 2574 ng/L
      at day 4 (p < 0.001) and to 2808 ng/L at day 30 (p = 0.002). Median CRP increased
      from 1.80 mg/L preoperatively to 136 mg/L at day 4 and returned to 6.12 mg/L at
      day 30 in the coronary bypass group. There was a significant decrease in
      myostatin concentrations both in the early and late postsurgical period. The
      lowest myostatin concentration time point coincided with the highest CRP
      concentration time point. 

PMID- 25749571
TI  - Test-retest reliability of the Muslim Religiosity Scale: follow-up to "Religious
      involvement and health among dialysis patients in Saudi Arabia".
AB  - The intra-class correlation coefficient for the scale was 0.961, 95 % CI 0.912
      0.983. We conclude that the MRS is a highly reliable measure of Muslim
      religiosity over time. 

PMID- 25749572
TI  - The ten barriers to appropriate management of patients at the end of their life.
AB  - The development of ICUs as the final option for seriously ill patients,
      especially the elderly frail patient at the end of his/her life, has meant that
      intensivists have increasingly taken on the role of diagnosing the dying. Our
      society, and even our medical colleagues, do not necessarily understand what we
      can achieve in ICUs, and even more importantly, what we cannot achieve. The next
      crucial step for us as individuals, and through our professional bodies, is to
      engage our society in discussions on our role and encourage debate and
      discussion, being aware of the controversies that will inevitably result.
      Birthing in the 1950s was medicalised without discussion with women and their
      families. In a similar manner, dying has been medicalised in the twenty-first
      century. It has not been a conspiracy and the use of futile and expensive
      treatment at the EoL transition is not necessarily anyone's choice. The specialty
      of intensive care has a particularly important role in facilitating discussions
      with our society in order to define different ways of managing dying.

PMID- 25749573
TI  - Ulcerative necrosis of the uvula following endotracheal intubation.

PMID- 25749574
TI  - Measuring diaphragm thickness with ultrasound in mechanically ventilated
      patients: feasibility, reproducibility and validity.

PMID- 25749576
TI  - Echocardiographic Diagnosis of Ventricular Tachycardia.

PMID- 25749575
TI  - Ginkgolide B protects against cisplatin-induced ototoxicity: enhancement of Akt
      Nrf2-HO-1 signaling and reduction of NADPH oxidase.
AB  - Cisplatin is a widely used chemotherapeutic drug for the treatment of various
      cancers. However, the ototoxicity severely limited its maximum dose. The present
      study was designed to evaluate the effect of Ginkgolide B (GB), a major component
      of Ginkgo biloba extracts, on cisplatin-induced ototoxicity and to elucidate the
      molecular mechanism in vitro and in vivo. In HEI-OC1 auditory cells, GB
      concentration-dependently inhibited the reduction of cell viability and increase
      in apoptosis exerted by cisplatin. Cisplatin-activated mitochondrial apoptotic
      molecular events were significantly inhibited by GB. In addition, GB notably
      suppressed the increase in NOX2 and p47(phox) expression and the decrease in
      nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1)
      expression in cisplatin-exposed cells. Inhibition of Nrf2 using SiRNA and
      blockage of HO-1 by zinc protoporphyrin IX (ZnPP) suppressed the protective
      effects of GB. Moreover, GB prevented cisplatin-induced reduction of Akt
      phosphorylation and LY294002, an inhibitor of PI3 K/Akt signaling, blocked the
      anti-apoptotic effect of GB in cisplatin-treated cells. Furthermore, the
      protective effect of GB was tested in cisplatin-exposed rats. GB treatment
      markedly protected animals against cisplatin-induced hearing loss and vestibular
      dysfunction. Inhibition of Akt and HO-1 significantly suppressed the improvement
      in hearing loss and vestibular dysfunction in GB-treated rats. We demonstrate
      that GB decreases ROS generation through reducing NOX2 expression and enhancing
      activity through Akt-Nrf2-HO-1 pathway, resulting in inhibition of mitochondrial
      apoptosis and final reduction of cisplatin-induced ototoxicity in vitro and in
      vivo. Our findings have gained an insight into the mechanism of GB-exerted
      protective effect against cisplatin-induced ototoxicity. 

PMID- 25749577
TI  - Reliability and validity of the Turkish pediatric Voice Handicap index.
AB  - OBJECTIVES: The aim of this study is to develop a Turkish version of the
      pediatric voice index (pVHI) and to evaluate its reliability and validity for
      cultural adaptation. METHODS: The original pVHI was translated to Turkish. It was
      administered to 151 parents of 40 dysphonic children and 111 non-dysphonic
      children. A cross-sectional descriptive model is used with two-sample
      methodology. The reliability, validity measures, sensitivity, specifity and
      receiver operating characteristics (ROC) analysis with AUC values were
      calculated. RESULTS: The findings showed that the Turkish version of the pVHI had
      highly significant validity, reliability and excellent internal consistency,
      sensitivity and specifity for functional, physical and emotional domains and the
      total score. CONCLUSIONS: The Turkish version of the pVHI is a valid and reliable
      tool to assess the parents' perception about their children with voice disorders.

PMID- 25749578
TI  - Quantification of Corticospinal Tracts with Diffusion Tensor Imaging in Brainstem
      Surgery: Prognostic Value in 14 Consecutive Cases at 3T Magnetic Resonance
      Imaging.
AB  - OBJECTIVE: In this study, we investigated the potential prognostic role of
      morphologic and quantitative diffusion tensor imaging (DTI) in patients with
      brainstem cavernoma (BSC) in terms of postoperative outcome. METHODS: In this
      retrospective study of 14 brainstem cavernoma patients, we analyzed pre- and
      postoperative DTI data. White matter tractography of corticospinal tracts (CSTs)
      was performed with the Fiber Assignment by Continuous Tracking algorithm, and
      morphologic characteristics of CSTs were compared with clinically assessed motor
      strength. Fractional anisotropy (FA) and apparent diffusion coefficient (ADC)
      were measured in ipsi- and contralesional regions of interest at the lesion
      level, as well as levels caudal and rostral to the lesion. Correlation analysis
      was performed between lateral index (LI) of ipsi-/contralateral FA and ADC values
      and patients' motor function. RESULTS: Preoperatively, normal morphologic
      features of CSTs corresponded to normal motor function in 4 patients. The other
      10 morphologically abnormal preoperative CSTs didn't show corresponding motor
      impairment either in pre- or postoperative follow-up period. The sensitivity,
      specificity, positive predictive, and negative predictive values of white matter
      tractographic morphology on preoperative motor function were 100%, 57.1%, 70%,
      and 100%, respectively. The corresponding values on follow-up motor function were
      100%, 33.3%, 20%, and 100%, respectively. The mean FA at lesion level was
      significantly lower than the corresponding FA at the contralateral hemisphere (P
      = 0.009). In areas caudal to the lesion the same trend yet without statistic
      significance was observed (P = 0.23). There was no significant laterality
      difference of mean FAs rostral to the level of the lesion. No correlation in LI
      of FA or ADC in the 3 anatomic levels with simultaneous and long-term follow up
      motor function was observed. Restoration of the morphology of the affected CST
      postoperatively was associated with a trend for decreasing ADC compared with the
      preoperative measurements. CONCLUSION: Intact CST morphology in DTI predicts a
      favorable postoperative outcome in patients with BSC. Interrupted CSTs and
      decreased FA values correlate well within BSC lesion level; nevertheless,
      morphologic characteristics and diffusion parameter changes at lesion level
      cannot predict poor prognosis. Caudal and rostral diffusion parameters can
      provide more information of the integrity of CSTs compared with morphologic study
      alone.

PMID- 25749579
TI  - Outcomes After Surgery and Radiotherapy for Papillary Tumor of the Pineal Region.
AB  - BACKGROUND: Papillary tumor of the pineal region (PTPR) is a rare neuroectodermal
      tumor that was first described in 2003 and formally codified by the World Health
      Organization in 2007. Limited reports suggest surgical resection is the mainstay
      of treatment; however, the role of multimodality therapy is not well defined. We
      evaluated our institutional experience in the treatment of PTPR. METHODS: A
      retrospective review of 8 patients with pathologically confirmed PTPR diagnosed
      between 1999 and 2013 was performed. RESULTS: The median age at diagnosis was 37
      years (range, 25-56 years). After a median follow-up period of 60 months (range,
      10-170 months), 7 of 8 patients were still living. All patients underwent maximum
      safe surgical resection; 5 received adjuvant radiation (63%). Overall and
      progression-free survival 5 years after diagnosis were 100% and 51%,
      respectively. Progression-free survival 5 years after completion of adjuvant
      radiotherapy was 64%. Crude recurrence rates for patients receiving adjuvant
      radiotherapy (n = 5) and patients not receiving adjuvant radiotherapy (n = 3)
      were 20% and 67%, respectively. Crude recurrence rate after gross total resection
      (GTR) and no adjuvant radiotherapy (n = 2) was 100% versus 0% when adjuvant
      radiotherapy was administered after GTR (n = 2). After subtotal resection, 3
      patients received adjuvant radiotherapy; 1 of these patients had out-of-field
      recurrence at 46 months (crude recurrence rate 33%). In all cases, salvage with
      radiation at the time of recurrence was effective. CONCLUSIONS: Our institutional
      experience confirms a recent multicenter retrospective series showing excellent
      survival but high risk of local recurrence for PTPR. Our findings suggest that
      radiotherapy provides durable local control, particularly when administered in
      the adjuvant setting after GTR.

PMID- 25749580
TI  - Fighting Cancer on All Fronts: Stereotactic Radiosurgery and the Role for
      Aggressive Primary Treatment in Non-Small Cell Lung Cancer Patients with One
      Brain Metastasis.

PMID- 25749581
TI  - Multiportal Combined Transorbital Transnasal Endoscopic Approach for the
      Management of Selected Skull Base Lesions: Preliminary Experience.
AB  - BACKGROUND: Skull base lesions are challenging to treat and may be managed using
      several approaches each with its own advantages and limitations. In selected
      cases, a modular, combined, multiportal approach could overcome the limits of a
      single approach and respond well to the needs of the patient. METHODS: We report
      a preclinical study on 5 cadaveric specimens and 4 preliminary clinical
      experiences with the combined multiportal transnasal transorbital endoscopic
      approach for the management of selected complex skull base pathologies. The
      technical feasibility and safety of this combined approach were evaluated in the
      preclinical study. The applicability in vivo of such an approach, together with
      early and late complications, specific morbidity, and hospitalization time were
      analyzed in the preliminary clinical experiences. RESULTS: The transnasal
      endoscopic extended approach combined with the transorbital endoscopic approach
      offered greater visualization and tissue handling than a single approach alone
      could. The multiportal combined transorbital transnasal endoscopic approach was
      used effectively in vivo to resect 1 case of malignant schwannoma arising from
      the second branch of the trigeminal nerve and 3 cases of spheno-orbital
      meningioma without significant complications and with minimal morbidity for the
      patients. CONCLUSIONS: The multiportal combined transorbital transnasal
      endoscopic approach is a safe and effective procedure for management of selected
      complex skull base lesions that is able to capitalize on the advantages and
      overcome the limitations of each single approach. This combined approach offers a
      multiperspective view of the spaces and allows for a more synergized procedure,
      especially when dealing with multicompartmental lesions.

PMID- 25749583
TI  - Extinction during memory reconsolidation blocks recovery of fear in adolescents.
AB  - Adolescence is a time of intensified emotional experiences, during which anxiety
      and stress-related disorders peak. The most effective behavioral therapies for
      treating these disorders share exposure-based techniques as a core component.
      Exposure-based therapies build on the principles of fear extinction learning and
      involve desensitizing the individual to cues that trigger anxiety. Yet, recent
      evidence shows an adolescent-specific diminished capacity to extinguish fear
      responses, suggesting that adolescents may respond less well to exposure-based
      therapies than other age groups. Here we demonstrate an alternative method for
      blocking the recall of fear memories in adolescents, building on principles of
      memory reconsolidation in adults. During memory reconsolidation, a memory that is
      recalled becomes labile during which time it can be updated. Prior research has
      shown that extinction training during memory reconsolidation attenuates the
      recovery of fear memory in human adults and in rodents. Using this method, we
      show attenuation of fear memory in adolescent humans. These findings have
      significant implications for treating one of the most vulnerable populations to
      anxiety and stress related disorders - adolescents - by optimizing exposure
      therapy based on principles of memory reconsolidation. 

PMID- 25749582
TI  - BDNF-TrkB pathway mediates neuroprotection of hydrogen sulfide against
      formaldehyde-induced toxicity to PC12 cells.
AB  - Formaldehyde (FA) is a common environmental contaminant that has toxic effects on
      the central nervous system (CNS). Our previous data demonstrated that hydrogen
      sulfide (H2S), the third endogenous gaseous mediator, has protective effects
      against FA-induced neurotoxicity. As is known to all, Brain-derived neurotropic
      factor (BDNF), a member of the neurotrophin gene family, mediates its
      neuroprotective properties via various intracellular signaling pathways triggered
      by activating the tyrosine kinase receptor B (TrkB). Intriguingly, our previous
      data have illustrated the upregulatory role of H2S on BDNF protein expression in
      the hippocampus of rats. Therefore, in this study, we hypothesized that H2S
      provides neuroprotection against FA toxicity by regulating BDNF-TrkB pathway. In
      the present study, we found that NaHS, a donor of H2S, upregulated the level of
      BDNF protein in PC12 cells, and significantly rescued FA-induced downregulation
      of BDNF levels. Furthermore, we found that pretreatment of PC12 cells with K252a,
      an inhibitor of the BDNF receptor TrkB, markedly reversed the inhibition of NaHS
      on FA-induced cytotoxicity and ablated the protective effects of NaHS on FA
      induced oxidative stress, including the accumulation of intracellular reactive
      oxygen species (ROS), 4-hydroxy-2-trans-nonenal (4-HNE), and malondialdehyde
      (MDA). We also showed that K252a abolished the inhibition of NaHS on FA-induced
      apoptosis, as well as the activation of caspase-3 in PC12 cells. In addition,
      K252a reversed the protection of H2S against FA-induced downregulation of Bcl-2
      protein expression and upregulation of Bax protein expression in PC12 cells.
      These data indicate that the BDNF-TrkB pathway mediates the neuroprotection of
      H2S against FA-induced cytotoxicity, oxidative stress and apoptosis in PC12
      cells. These findings provide a novel mechanism underlying the protection of H2S
      against FA-induced neurotoxicity. 

PMID- 25749584
TI  - [Anemia in elderly patients admitted to an acute geriatric ward].
AB  - OBJECTIVE: To describe the characteristics, prevalence and prognostic of anemia
      in older patients admitted to an acute geriatric unit. MATERIAL AND METHODS: A
      prospective descriptive study was conducted on patients admitted to a geriatric
      unit. Anemia was defined using the World Health Organization criteria. A
      comprehensive geriatric assessment was performed on all patients. When possible,
      a telephone follow-up re-evaluation (mortality, functional status) was performed
      one year after discharge. RESULTS: A total of 145 patients were studied. The mean
      age was 81 years, and 93 (64.13%) were anemic. Chronic diseases and iron
      deficiency anemia were the most frequent. Anemic patients had lower scores in the
      Barthel Index (P<.05). The mortality one year after discharge was 47.9%, with no
      differences between anemic or non-anemic patients (OR 2.07, [0.98-4.4]). All the
      geriatric indexes (Barthel index; Charlson comorbidity index, Mini-mental state
      examination and Mini Nutritional Assessment) showed worse scores in patients who
      died one year after discharge. CONCLUSIONS: The prevalence of anemia in the
      elderly admitted to a geriatric unit is elevated, and associated with a poorer
      functional status.

PMID- 25749585
TI  - [New specialties, new skills. Identification of areas of personal and shared
      skills in the different health professions].

PMID- 25749586
TI  - The 5th Congress of the Brazilian Biotechnology Society (SBBIOTEC): Meeting
      abstracts.

PMID- 25749587
TI  - Use of 18F-FDG-PET-CT for Assessment of Response to Neoadjuvant Chemotherapy in
      Children With Wilms Tumor.
AB  - PURPOSE: The aim of this study was to evaluate the predictive value of fluorine
      18-fluorodeoxyglucose positron emission tomography with computed tomography (F
      FDG-PET-CT) in the assessment of histologic response to neoadjuvant chemotherapy
      in children with Wilms tumors (WTs). MATERIALS AND METHODS: We prospectively
      registered 12 patients with WTs who were treated with 2 cycles of neoadjuvant
      chemotherapy and surgery. All patients underwent sequential F-FDG-PET-CT before
      (PET-CT1) and after (PET-CT2) neoadjuvant chemotherapy. Maximum standardized
      uptake value (SUVmax) was measured on PET-CT1 (SUV1) and PET-CT2 (SUV2). The
      percentage change in SUVmax (SUVmax reduction) was calculated. After surgery the
      effects of neoadjuvant chemotherapy were graded histopathologically: >=90%
      necrosis indicated a good response and <90% necrosis was considered a poor
      response. The correlation between SUVmax reduction and histologic response was
      estimated using the Spearman correlation coefficient. RESULTS: Among the 12
      patients who underwent PET-CT before and after chemotherapy, SUVmax reduction was
      significantly different between the good response group and the poor response
      group (P=0.035). A significant, in terms of P value, correlation was found
      between pathologic response and SUVmax reduction (r=0.700; 95% confidence
      interval, 0.060-0.935; P=0.011). A threshold of 66% reduction in SUVmax was
      identified, with which partition, there were 8 good histologic responders (>=66%
      decrease in SUVmax) and 4 poor responders. The histologic complete response rate
      of the good responders was 87.5%, whereas that of poor responders was 0%. SUV1>=7
      and SUV2>=2.4 were both considered to be with high risk of recurrence. In
      patients with SUV1>=7, 4/5 cases relapsed and 4/6 patients with SUV2>=2.4
      relapsed. CONCLUSIONS: As there seems to be a good correlation of changes in
      SUVmax and histologic response, PET-CT has the potential of predicting the
      response to neoadjuvant chemotherapy in children with WT. SUV1 and SUV2 by
      themselves might be a good prognosticator of the clinical outcome of WT pediatric
      patients treated with International Society of Pediatric Oncology protocols,
      although the reduction rate of SUVmax is much less powerful for prognosis.

PMID- 25749588
TI  - Advancing the science of integrative oncology to inform patient-centered care for
      cancer survivors.

PMID- 25749589
TI  - Survivorship care planning: unique opportunity to champion integrative oncology?

PMID- 25749590
TI  - National Cancer Institute's support of research to further integrative oncology
      practice.

PMID- 25749591
TI  - Building the evidence base for integrative approaches to care of cancer
      survivors.

PMID- 25749592
TI  - Integrative oncology and wellness considerations in cancer survivorship.

PMID- 25749593
TI  - A patients' perspective on integrative oncology: getting past the "war," living
      with and beyond cancer.

PMID- 25749594
TI  - Advancing the evidence base and transforming cancer care through
      interprofessional collegiality: the society for integrative oncology.

PMID- 25749596
TI  - Expectancy in real and sham electroacupuncture: does believing make it so?
AB  - BACKGROUND: The large placebo effect observed in prior acupuncture trials
      presents a substantial challenge for interpretation of the efficacy of
      acupuncture. We sought to evaluate the relationship between response expectancy,
      a key component of the placebo effect over time, and treatment outcome in real
      and sham electroacupuncture (EA). METHODS: We analyzed data from a randomized
      controlled trial of EA and sham acupuncture (SA) for joint pain attributable to
      aromatase inhibitors among women with breast cancer. Responders were identified
      using the Patient Global Impression of Change instrument at Week 8 (end of
      intervention). The Acupuncture Expectancy Scale (AES) was used to measure
      expectancy four times during the trial. Linear mixed-effects models were used to
      evaluate the association between expectancy and treatment response. RESULTS: In
      the wait list control group, AES remained unchanged over treatment. In the SA
      group, Baseline AES was significantly higher in responders than nonresponders
      (15.5 vs 12.1, P = .005) and AES did not change over time. In the EA group,
      Baseline AES scores did not differ between responders and nonresponders (14.8 vs
      15.3, P = .64); however, AES increased in responders compared with nonresponders
      over time (P = .004 for responder and time interaction term) with significant
      difference at the end of trial for responders versus nonresponders (16.2 vs 11.7,
      P = .004). CONCLUSIONS: Baseline higher response expectancy predicts treatment
      response in SA, but not in EA. Divergent mechanisms may exist for how SA and EA
      influence pain outcomes, and patients with low expectancy may do better with EA
      than SA.

PMID- 25749597
TI  - Tailoring mind-body therapies to individual needs: patients' program preference
      and psychological traits as moderators of the effects of mindfulness-based cancer
      recovery and supportive-expressive therapy in distressed breast cancer survivors.
AB  - BACKGROUND: Mindfulness-based cancer recovery (MBCR) and supportive-expressive
      therapy (SET) are well-validated psycho-oncological interventions, and we have
      previously reported health benefits of both programs. However, little is known
      about patients' characteristics or program preferences that may influence
      outcomes. Therefore, this study examined moderators of the effects of MBCR and
      SET on psychological well-being among breast cancer survivors. METHODS: A multi
      site randomized controlled trial was conducted between 2007 and 2012 in two
      Canadian cities (Calgary and Vancouver). A total of 271 distressed stage I-III
      breast cancer survivors were randomized into MBCR, SET or a 1-day stress
      management seminar (SMS). Baseline measures of moderator variables included
      program preference, personality traits, emotional suppression, and repressive
      coping. Outcome measures of mood, stress symptoms, quality of life, spiritual
      well-being, post-traumatic growth, social support, and salivary cortisol were
      measured pre- and post intervention. Hierarchical regression analyses were used
      to assess moderator effects on outcomes. RESULTS: The most preferred program was
      MBCR (55%). Those who were randomized to their preference improved more over time
      on quality of life and spiritual well-being post-intervention regardless of the
      actual intervention type received. Women with greater psychological morbidity at
      baseline showed greater improvement in stress symptoms and quality of life if
      they received their preferred versus nonpreferred program. CONCLUSIONS: Patients'
      program preference and baseline psychological functioning, rather than
      personality, were predictive of program benefits. These results suggest
      incorporating program preference can maximize the efficacy of integrative
      oncology interventions, and emphasize the methodological importance of assessing
      and accommodating for preferences when conducting mind-body clinical trials.

PMID- 25749595
TI  - Tai chi, cellular inflammation, and transcriptome dynamics in breast cancer
      survivors with insomnia: a randomized controlled trial.
AB  - BACKGROUND: Mind-body therapies such as Tai Chi are widely used by breast cancer
      survivors, yet effects on inflammation are not known. This study hypothesized
      that Tai Chi Chih (TCC) would reduce systemic, cellular, and genomic markers of
      inflammation as compared with cognitive behavioral therapy for insomnia (CBT-I).
      METHODS: In this randomized trial for the treatment of insomnia, 90 breast cancer
      survivors with insomnia were assigned to TCC or CBT-I for 2-hour sessions weekly
      for 3 months. At baseline and postintervention, blood samples were obtained for
      measurement of C-reactive protein and toll-like receptor-4-activated monocyte
      production of interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF), with a
      random subsample (n = 48) analyzed by genome-wide transcriptional profiling.
      RESULTS: Levels of C-reactive protein did not change in the TCC and CBT-I groups.
      Levels of toll-like receptor-4-activated monocyte production of IL-6 and TNF
      combined showed an overall reduction in TCC versus CBT-I (P < .02), with similar
      effects for IL-6 (P = .07) and TNF (P < .05) alone. For genome-wide
      transcriptional profiling of circulating peripheral blood mononuclear cells,
      expression of genes encoding proinflammatory mediators showed an overall
      reduction in TCC versus CBT-I (P = .001). TELiS promoter-based bioinformatics
      analyses implicated a reduction of activity of the proinflammatory transcription
      factor, nuclear factor-kappaB, in structuring these differences. CONCLUSIONS:
      Among breast cancer survivors with insomnia, 3 months of TCC reduced cellular
      inflammatory responses, and reduced expression of genes encoding proinflammatory
      mediators. Given the link between inflammation and cancer, these findings provide
      an evidence-based molecular framework to understand the potential salutary
      effects of TCC on cancer survivorship.

PMID- 25749598
TI  - Does a community-based stress management intervention affect psychological
      adaptation among underserved black breast cancer survivors?
AB  - BACKGROUND: In this randomized trial, Project CARE, we examined whether
      participation in a cognitive-behavioral stress management and breast cancer
      wellness and education program improved psychological outcomes among a sample of
      underserved black breast cancer survivors. METHODS: Both complementary medicine
      interventions were 10-sessions, manualized, group-based, and were culturally
      adapted for black women in the community from evidence-based interventions.
      Participants were 114 black women (mean age = 51.1, 27-77 years) who had
      completed breast cancer treatment 0-12 months before enrollment (stages 0-IV,
      mean time since cancer diagnosis = 14.1 months). Women were enrolled upon
      completion of curative treatment (ie, surgical, chemotherapy, radiation oncology)
      and randomized to receive cognitive-behavioral stress management or cancer
      wellness and education program. RESULTS: There was a remarkable 95% retention
      rate from baseline to 6-month follow-up. Participants in both conditions showed
      statistically significant improvement on indices of psychological well-being,
      including overall quality of life (Functional Assessment of Cancer Therapy
      Breast), intrusive thoughts (Impact of Event Scale-Revised), depressive symptoms
      (Center for Epidemiologic Studies-Depression), and stress levels (Perceived
      Stress Scale) over the 6-month postintervention follow-up (all repeated measures
      analysis of variance within-subjects time effects: P < .05, except for overall
      mood; Profile of Mood States-Short Version). Contrary to hypotheses, however,
      condition * time effects were not statistically significant. CONCLUSIONS:
      Findings suggest that improvements in multiple measures over time may have been
      due to intensive training in stress management, extensive provision of breast
      cancer information, or participation in an ongoing supportive group of
      individuals from a similar racial background. Implications bear on decisions
      about appropriate control groups, the timing of intervention delivery during the
      treatment trajectory, and perceived support from the research team.

PMID- 25749599
TI  - Associations between healthy lifestyle behaviors and complementary and
      alternative medicine use: integrated wellness.
AB  - BACKGROUND: Conventional medicine, lifestyle modification, and complementary and
      alternative medicine (CAM) are potential strategies to decrease the risk of late
      effects in pediatric cancer survivors. This study aimed to compare the
      characteristics and usage patterns of CAM and lifestyle therapies among survivors
      of childhood cancer. METHODS: We report the results of a cross sectional survey
      comparing usage patterns of CAM and lifestyle therapies among childhood cancer
      survivors. CAM therapies were defined by NCCAM classifications and lifestyle
      therapies were defined as dietary changes, conventional supplements with dietary
      reference intake values, and exercise. RESULTS: One hundred fifty-five (95%)
      patients approached in person and 45 (34%) patients approached by mail consented
      to participate. Sixty-eight used at least one lifestyle therapy and 58% used at
      least one CAM therapy. CAM users had 4.7 times the odds of using lifestyle
      therapies than non-CAM users (P < .0001); the odds of using dietary change and
      conventional supplements was greater in CAM users than non-CAM users (odds ratio
      [OR] = 3.55, P < .0001 and OR = 4.80, P < .0001 respectively). Use of the top
      three CAM therapies was associated with overall lifestyle therapy use (OR = 12.52
      and P < .0001, OR = 7.071 and P = .0004, and OR = 2.925 and P = .0089 for
      juicing, yoga/movement, and touch therapies, respectively). Lifestyle therapies
      and CAM had similar perceived efficacy (92%-90%, respectively). CONCLUSIONS: This
      data reports a strong association between CAM and lifestyle therapies and may
      identify a population with commitment to general wellness. Use of one therapy may
      promote use of other therapies and this potential synergistic relationship can be
      targeted in future interventions.

PMID- 25749600
TI  - Effects of integrative medicine on pain and anxiety among oncology inpatients.
AB  - BACKGROUND: Few studies have investigated the effectiveness of integrative
      medicine (IM) therapies on pain and anxiety among oncology inpatients. METHODS:
      Retrospective data obtained from electronic medical records identified patients
      with an oncology International Classification of Diseases-9 code who were
      admitted to a large Midwestern hospital between July 1, 2009 and December 31,
      2012. Outcomes were change in patient-reported pain and anxiety, rated before and
      after individual IM treatment sessions, using a numeric scale (0-10). RESULTS: Of
      10948 hospital admissions over the study period, 1833 (17%) included IM therapy.
      Older patients had reduced odds of receiving any IM therapy (odds ratio [OR]:
      0.97, 95% confidence interval [95% CI] = 0.96 to 0.98) and females had 63% (OR:
      1.63, 95% CI = 1.38 to 1.92) higher odds of receiving any IM therapy compared
      with males. Moderate (OR: 1.97, 95% CI = 1.61 to 2.41), major (OR: 3.54, 95% CI =
      2.88 to 4.35), and extreme (OR: 5.96, 95% CI = 4.71 to 7.56) illness severity
      were significantly associated with higher odds of receiving IM therapy compared
      with admissions of minor illness severity. After receiving IM therapy, patients
      averaged a 46.9% (95% CI = 45.1% to 48.6%, P <.001) reduction in pain and a 56.1%
      (95% CI = 54.3% to 58.0%, P <.001) reduction in anxiety. Bodywork and traditional
      Chinese Medicine therapies were most effective for reducing pain, while no
      significant differences among therapies for reducing anxiety were observed.
      CONCLUSIONS: IM services to oncology inpatients resulted in substantial decreases
      in pain and anxiety. Observational studies using electronic medical records
      provide unique information about real-world utilization of IM. Future studies are
      warranted and should explore potential synergy of opioid analgesics and IM
      therapy for pain control.

PMID- 25749601
TI  - A hybrid effectiveness-implementation trial of an evidence-based exercise
      intervention for breast cancer survivors.
AB  - BACKGROUND: The primary aims of this hybrid Type 1 effectiveness-implementation
      trial were to quantitatively assess whether an evidence-based exercise
      intervention for breast cancer survivors, Strength After Breast Cancer, was safe
      and effective in a new setting and to qualitatively assess barriers to
      implementation. METHODS: A cohort of 84 survivors completed measurements related
      to limb volume, muscle strength, and body image at baseline, 67 survivors
      completed measurements 12 months later. Qualitative methods were used to
      understand barriers to implementation experienced by referring oncology
      clinicians and physical therapists who delivered the program. RESULTS: Similar to
      the efficacy trial, the revised intervention demonstrated safety with regard to
      lymphedema, and led to improvements in lymphedema symptoms, muscular strength,
      and body image. Comparison of effects in the effectiveness trial to effects in
      the efficacy trial revealed larger strength increases in the efficacy trial than
      in the effectiveness trial (P < .04), but few other differences were found.
      Qualitative implementation data suggested significant barriers around
      intervention characteristics, payment, eligibility criteria, the referral
      process, the need for champions (ie, advocates), and the need to adapt during
      implementation of the intervention, which should be considered in future
      dissemination and implementation efforts. CONCLUSIONS: This trial successfully
      demonstrated that a physical therapy led strength training program for breast
      cancer survivors can be implemented in a community setting while retaining the
      effectiveness and safety of the clinical trial. However, during the translation
      process, strategies to reduce barriers to implementation are required. This new
      program can inform larger scale dissemination and implementation efforts.

PMID- 25749606
TI  - Women in science.

PMID- 25749607
TI  - Compensation of matrix effects in a standard addition method for metformin in
      postmortem blood using liquid chromatography-electrospray-tandem mass
      spectrometry.
AB  - This work describes a procedure to evaluate matrix effects in a combined dilution
      and standard addition method (SAM) using liquid chromatography-electrospray
      tandem mass spectrometry. The method was validated and applied to an analysis of
      metformin in postmortem blood samples. The analytical method included protein
      precipitation with methanol, followed by liquid chromatographic separation of
      metformin on Gemini NX-C18 reversed-phase column using a gradient consisting of
      methanol and ammonium acetate at pH 3.2. The mass spectrometric analysis was
      performed with a quadrupole-linear ion trap mass spectrometer equipped with a
      turbo ion spray interface in a positive ion mode using selected reaction
      monitoring. Quantitation was performed based on an SAM. Validation for metformin
      revealed a practical limit of quantification of 0.1 mg/L, a linear range from 0.1
      to 3.0 mg/L, average precision 10%, accuracy (bias) 9% and reproducibility 10%.
      Combined matrix effects were evaluated by k-values (slopes) of calibration plots,
      postextraction addition approach and a comparison of within- and between-sample
      precision (relative standard deviation). It was demonstrated that the method
      contained matrix effects which were fully compensated for using dilution and the
      SAM. 

PMID- 25749609
TI  - Systematic nasogastric tube in aortic surgery: is it necessary?
AB  - BACKGROUND: Routine nasogastric tube (NGT) decompression has been traditionally
      used to prevent nausea and vomiting after abdominal surgery. Besides, many
      studies having demonstrated no benefits derived from this practice after an
      elective laparotomy, little evidence has been published regarding its use in
      aortic surgery. In this study, we analyze the effects of the selective use of the
      NGT in patients undergoing infrarenal aortic surgery in our center. METHODS:
      Prospective cohort study including patients who underwent elective infrarenal
      aortic surgery between January 2011 and December 2012. Patients were
      prospectively included in group A (systematic NGT placement) and group B
      (nonsystematic NGT). The main end point was the occurrence of postoperative
      nausea and vomiting (PONV). Secondary end points were postoperative
      complications, time to first oral intake, and hospital stay. RESULTS: One hundred
      patients were finally included in the study, 50 patients per group. Preoperative
      and intraoperative data were similar between both groups. Higher incidence of
      PONV (48% vs. 10%; relative risk, 2.4; 95% confidence interval [CI], 1.3-4.5; P =
      0.003) was observed in group A. Selective NGT behaved as a protective factor
      regarding earlier first oral intake in first postoperative 48 hours (hazard
      ratio, 0.67; 95% CI, 0.45-0.99; P = 0.05). There were no differences in other
      adverse events although a trend toward fewer respiratory complications was
      observed in patients with nonsystematic NGT. CONCLUSIONS: This study demonstrates
      higher incidence of PONV and longer time to first oral intake in patients with
      systematic NGT with no benefits derived from this practice. Based on these
      results, selective NGT decompression should be encouraged in patients undergoing
      infrarenal aortic surgery.

PMID- 25749602
TI  - Clinical practice guidelines on the use of integrative therapies as supportive
      care in patients treated for breast cancer.
AB  - BACKGROUND: The majority of breast cancer patients use complementary and/or
      integrative therapies during and beyond cancer treatment to manage symptoms,
      prevent toxicities, and improve quality of life. Practice guidelines are needed
      to inform clinicians and patients about safe and effective therapies. METHODS:
      Following the Institute of Medicine's guideline development process, a systematic
      review identified randomized controlled trials testing the use of integrative
      therapies for supportive care in patients receiving breast cancer treatment.
      Trials were included if the majority of participants had breast cancer and/or
      breast cancer patient results were reported separately, and outcomes were
      clinically relevant. Recommendations were organized by outcome and graded based
      upon a modified version of the US Preventive Services Task Force grading system.
      RESULTS: The search (January 1, 1990-December 31, 2013) identified 4900 articles,
      of which 203 were eligible for analysis. Meditation, yoga, and relaxation with
      imagery are recommended for routine use for common conditions, including anxiety
      and mood disorders (Grade A). Stress management, yoga, massage, music therapy,
      energy conservation, and meditation are recommended for stress reduction,
      anxiety, depression, fatigue, and quality of life (Grade B). Many interventions
      (n = 32) had weaker evidence of benefit (Grade C). Some interventions (n = 7)
      were deemed unlikely to provide any benefit (Grade D). Notably, only one
      intervention, acetyl-l-carnitine for the prevention of taxane-induced neuropathy,
      was identified as likely harmful (Grade H) as it was found to increase
      neuropathy. The majority of intervention/modality combinations (n = 138) did not
      have sufficient evidence to form specific recommendations (Grade I). CONCLUSIONS:
      Specific integrative therapies can be recommended as evidence-based supportive
      care options during breast cancer treatment. Most integrative therapies require
      further investigation via well-designed controlled trials with meaningful
      outcomes.

PMID- 25749608
TI  - Thiazide Diuretics in Chronic Kidney Disease.
AB  - Widely prevalent in the general population, chronic kidney disease (CKD) is
      frequently complicated with hypertension. Control of hypertension in this high
      risk population is a major modifiable cardiovascular and renal risk factor but
      often requires multiple medications. Although thiazides are an attractive agent,
      guidelines have previously recommended against thiazide use in stage 4 CKD. We
      review the updated guidelines on thiazide use in advanced CKD, the
      antihypertensive mechanism of thiazides, and the clinical studies of thiazides in
      CKD. Older uncontrolled studies have shown that metolazone reduces blood pressure
      in CKD, but more recently small randomized controlled trials of
      hydrochlorothiazide in CKD have shown significant improvement in mean arterial
      pressure of 15 mmHg. Two recent uncontrolled studies of chlorthalidone including
      one that used ambulatory blood pressure monitoring found significant improvements
      in blood pressure. These findings all suggest that thiazides may be efficacious
      even in advanced CKD; however, electrolyte abnormalities were common in the
      studies reviewed so close monitoring is necessary during use. Adequately powered
      randomized trials are now needed before the routine use of thiazide diuretics in
      advanced CKD can be recommended. 

PMID- 25749610
TI  - An adult case of idiopathic internal carotid-internal jugular vein arteriovenous
      fistula.
AB  - Carotid-jugular fistula is an abnormal connection between the carotid artery
      and/or its branches and jugular vein. It can develop either because of trauma or
      spontaneous causes. Traumatic fistula may occur after head injuries and can range
      from minor falls to severe penetrating wounds. Traumatic fistula may also result
      from endovascular therapy; however, these fistulas may be congenital
      arteriovenous connections that open spontaneously in the setting of collagen
      vascular disease, atherosclerotic disease, hypertension, or childbirth.
      Spontaneous fistulas between internal carotid artery and internal jugular vein
      are very exceptional diseases; therefore, this case is presented for its rare
      incidence in literature. 

PMID- 25749611
TI  - Appendages of the cyanobacterial cell.
AB  - Extracellular non-flagellar appendages, called pili or fimbriae, are widespread
      in gram-negative bacteria. They are involved in many different functions,
      including motility, adhesion, biofilm formation, and uptake of DNA. Sequencing
      data for a large number of cyanobacterial genomes revealed that most of them
      contain genes for pili synthesis. However, only for a very few cyanobacteria
      structure and function of these appendages have been analyzed. Here, we review
      the structure and function of type IV pili in Synechocystis sp. PCC 6803 and
      analyze the distribution of type IV pili associated genes in other cyanobacteria.
      Further, we discuss the role of the RNA-chaperone Hfq in pilus function and the
      presence of genes for the chaperone-usher pathway of pilus assembly in
      cyanobacteria. 

PMID- 25749612
TI  - p38 MAP Kinase Inhibition Reduces Propionibacterium acnes-Induced Inflammation in
      Vitro.
AB  - INTRODUCTION: Propionibacterium acnes, a ubiquitous skin bacterium, stimulates
      keratinocytes to produce a number of proinflammatory cytokines and may contribute
      to inflammatory acne. The aim of the study was to investigate whether P. acnes
      induced proinflammatory cytokine release is mediated by P. acnes-induced
      activation of p38 mitogen-activated protein kinase (p38 MAPK or p38) in human
      keratinocytes. METHODS: Immunohistochemistry was used to evaluate p38
      phosphorylation in human skin samples with or without acne. Primary human
      keratinocytes and epidermal skin equivalents were exposed to viable P. acnes.
      Phosphorylation of MAPKs without or with p38 inhibitors was examined by Western
      blot and cytokine secretion was detected by Enzyme-Linked Immunosorbent Assay
      (ELISA). RESULTS: Increased levels of phospho-p38 were observed in human acne
      lesions, predominantly in follicular and perifollicular keratinocytes. Exposure
      of cultured human keratinocytes to viable P. acnes resulted in phosphorylation of
      multiple members of the MAPK family, including rapid and transient activation of
      p38 and extracellular signal-related kinase (ERK1/2) and relatively slow but
      sustained activation of c-Jun N-terminal kinases (JNK1/2). Viable P. acnes
      induced the secretion of interleukin-1alpha (IL-1alpha), tumor necrosis factor
      alpha (TNF-alpha), and IL-8 from human keratinocytes. The phosphorylation of p38
      (phospho-p38) and the secretion of cytokines induced by P. acnes in cultured
      keratinocytes were inhibited by SB203580, a p38alpha/beta inhibitor. Furthermore,
      SCIO-469, a selective inhibitor of p38alpha, showed similar effects in cultured
      keratinocytes. Topical treatment of SCIO-469 inhibited the P. acnes-induced
      phospho-p38 and cytokine secretion in human epidermal equivalents. CONCLUSION:
      The data demonstrate that P. acnes induces p38-dependent inflammatory responses
      in keratinocytes, and suggest that p38 may play an important role in the
      pathogenesis of inflammatory acne. FUNDING: Johnson & Johnson.

PMID- 25749613
TI  - Predictive factors of recurrence and malignant transformation in vocal cord
      leukoplakia.
AB  - The aim of this study was to define the predictive risk factors of vocal cord
      leukoplakia recurrence and malignant transformation. From January 2009 to
      December 2013, 63 patients with a diagnosis of vocal cord leukoplakia were
      identified based on their medical records. The 63 patients comprised 62 males and
      one female. This study showed that the extent of vocal cord leukoplakia resulted
      in statistically significant differences for both the recurrence of vocal cord
      leukoplakia and malignant transformation (p < 0.05). In addition, this study
      revealed that the degree of dysplasia resulted in statistically significant
      differences for both the recurrence of vocal cord leukoplakia and malignant
      transformation (p < 0.05). We suggest that the extent of lesion and the degree of
      dysplasia are predictive factors for the risk of recurrence and malignant
      transformation.

PMID- 25749614
TI  - Balloon catheter dilation technology combined with a fibrolaryngoscope to treat a
      maxillary sinus cyst.
AB  - A prospective randomized controlled study was conducted to investigate the effect
      of balloon catheter dilation technology combined with a fibrolaryngoscope in the
      treatment of a maxillary sinus cyst. The clinical data of 14 cases (19 maxillary
      sinuses) with balloon catheter dilation technology combined with a
      fibrolaryngoscope to remove sinus cysts (balloon group) and 16 cases (23
      maxillary sinuses) with conventional nasal endoscopic sinus surgery to remove
      sinus cysts (conventional group) were analyzed. All cases have completed the
      preoperative and postoperative SNOT-20, nasal endoscopy and coronal sinus CT
      scan. Lund-Kennedy endoscopic and Lund-Mackay CT scan staging scores were
      recorded. All patients were followed up for 24 weeks after the operation. The
      SNOT-20 scores, Lund-Kennedy endoscopic and Lund-Mackay CT scan staging scores
      were lower in the balloon group than that in the control group. Balloon catheter
      dilation technology combined with a fibrolaryngoscope can effectively preserve
      the function and structures of the nasal cavity and sinus, making it a good
      choice in the treatment of a retention cyst of the maxillary sinus.

PMID- 25749615
TI  - Influence of middle ear mucosal condition on post-tympanoplasty audiologic
      outcome.
AB  - In this study, the association between the middle ear mucosal condition and post
      tympanoplasty audiologic outcome was investigated in patients with chronic otitis
      media without cholesteatoma. One hundred and forty-three patients with chronic
      otitis media were collected in the Department of Otorhinolaryngology-Head and
      Neck Surgery at Asan Medical Center between January, 2009 and December, 2011. In
      the course of tympanoplasty, the status of the middle ear mucosa was divided into
      normal or abnormal by one surgeon. Pure tone audiometry was performed
      preoperatively and postoperatively, and post-tympanoplasty tympanogram was also
      conducted to estimate the condition of middle ear cavity. Of the 143 patients,
      there were 73 patients with normal middle ear mucosa and 70 patients with
      abnormal middle ear mucosa around Eustachian tube opening. The mean ABG of
      subjects with normal middle ear mucosa was 20.1 dB preoperatively, and 9.7 dB
      postoperatively (p < 0.001). Preoperative mean ABG was 22.4 dB and postoperative
      mean ABG was 16.4 dB in abnormal middle ear mucosa group (p = 0.137).
      Postoperative ABGs for 500 and 1000 Hz (7.1, 7.7 dB) in normal middle ear mucosa
      patients were significantly lower than those (17.2, 19.4 dB) in abnormal middle
      ear mucosa patients (p < 0.001). There was statistically significant correlation
      between middle ear mucosa status and post-tympanoplasty audiologic outcomes. The
      better condition of middle ear ventilation, the better postoperative hearing
      thresholds revealed after tympanoplasty.

PMID- 25749616
TI  - Ultrasonography in the diagnosis of nasal bone fractures: a comparison with
      conventional radiography and computed tomography.
AB  - The purpose of this study was to evaluate and compare the diagnostic efficacy of
      ultrasonography (US) with radiography and multi-detector computed tomography (CT)
      for the detection of nasal bone fractures. Forty-one patients with a nasal bone
      fracture who underwent prospective US examinations were included. Plain
      radiographs and CT images were obtained on the day of trauma. For US
      examinations, radiologist used a linear array transducer (L17-5 MHz) in 24
      patients and hockey-stick probe (L15-7 MHz) in 17. The bony component of the nose
      was divided into three parts (right and left lateral nasal walls, and midline of
      nasal bone). Fracture detection by three modalities was subjected to analysis.
      Furthermore, findings made by each modality were compared with intraoperative
      findings. Nasal bone fractures were located in the right lateral wall (n = 28),
      midline of nasal bone (n = 31), or left lateral wall (n = 31). For right and left
      lateral nasal walls, CT had greater sensitivity and specificity than US or
      radiography, and better agreed with intraoperative findings. However, for midline
      fractures of nasal bone, US had higher specificity, positive predictive value,
      and negative predictive value than CT. Although two US evaluations showed good
      agreements at all three sites, US findings obtained by the hockey-stick probe
      showed closer agreement with intraoperative findings for both lateral nasal wall
      and midline of nasal bone. Although CT showed higher sensitivity and specificity
      than US or radiography, US found to be helpful for evaluating the midline of
      nasal bone. Furthermore, for US examinations of the nasal bone, a smaller probe
      and higher frequency may be required.

PMID- 25749617
TI  - Quantification and localization of hesperidin and rutin in Citrus sinensis
      grafted on C. limonia after Xylella fastidiosa infection by HPLC-UV and MALDI
      imaging mass spectrometry.
AB  - A high performance liquid chromatography-ultraviolet (HPLC-UV) method was
      developed for quantifying hesperidin and rutin levels in leaves and stems of
      Citrus limonia, with a good linearity over a range of 1.0-80.0 and 1.0-50.0 MUg
      mL(-1) respectively, with r(2)>0.999 for all curves. The limits of detection
      (LOD) for both flavonoids were 0.6 and 0.5 MUg mL(-1), respectively, with
      quantification (LOQ) being 2.0 and 1.0 MUg mL(-1), respectively. The
      quantification method was applied to Citrus sinensis grafted onto C. limonia with
      and without CVC (citrus variegated chlorosis) symptoms after Xylella fastidiosa
      infection. The total content of rutin was low and practically constant in all
      analyses in comparison with hesperidin, which showed a significant increase in
      its amount in symptomatic leaves. Scanning electron microscopy studies on leaves
      with CVC symptoms showed vessel occlusion by biofilm, and a crystallized material
      was noted. Considering the difficulty in isolating these crystals for analysis,
      tissue sections were analyzed by matrix-assisted laser desorption/ionization mass
      spectrometry imaging (MALDI MSI) to confirm the presence of hesperidin at the
      site of infection. The images constructed from MS/MS data with a specific
      diagnostic fragment ion (m/z 483) also showed higher ion intensities for it in
      infected plants than in healthy ones, mainly in the vessel regions. These data
      suggest that hesperidin plays a role in the plant-pathogen interaction, probably
      as a phytoanticipin. This method was also applied to C. sinensis and C. limonia
      seedlings, and comparison with the graft results showed that the rootstock had an
      increased hesperidin content ~3.6 fold greater in the graft stem than in the stem
      of C. sinensis seedlings. Increase in hesperidin content by rootstock can be
      related to induced internal defense mechanisms.

PMID- 25749618
TI  - Isolation and structural elements of a water-soluble free radical scavenger from
      Nyctanthes arbor-tristis leaves.
AB  - The leaves of Nyctanthes arbor-tristis L. (Oleaceae) are used in Ayurvedic
      medicine for the management of a range of diseases, but reports on its
      phytochemicals and pharmacological properties are inadequate. Herein, we report
      purification of an antioxidative polysaccharide (F2) extracted from its leaves by
      water. The presence of a highly branched polysaccharide (75 kDa) containing
      esterified phenolic acids was revealed by chemical, chromatographic and
      spectroscopic analyses. Particularly, ESMS analysis of per acetylated oligomeric
      fragments derived by Smith degradation provides important structural information
      on a spectrum of glycerol tagged oligosaccharides. This polysaccharide showed
      dose dependent free radical scavenging capacity as evidenced by DPPH and Ferric
      reducing power assay. This pharmacologically active compound (F2) formed a water
      soluble complex with bovine serum albumin over pH 4.0-7.4. Accordingly,
      traditional aqueous extraction method provides a molecular entity that induces a
      pharmacological effect: this could epitomize a smart approach in phytotherapeutic
      management.

PMID- 25749619
TI  - Novel synthesis of thick wall coatings of titania supported Bi poisoned Pd
      catalysts and application in selective hydrogenation of acetylene alcohols in
      capillary microreactors.
AB  - Catalysis in microreactors allows reactions to be performed in a very small
      volume, reducing the environmental problems and greatly intensifying the
      processes through easy pressure control and the elimination of heat- and mass
      transfer limitations. In this study, we report a novel method for the controlled
      synthesis of micrometre-thick mesoporous TiO2 catalytic coatings on the walls of
      long channels (>1 m) of capillary microreactors in a single deposition step. The
      method uses elevated temperature and introduces a convenient control parameter of
      the deposition rate (displacement speed controlled by a stepper motor), which
      allows deposition from concentrated and viscous sols without channel clogging. A
      capillary microreactor wall-coated with titania supported Bi-poisoned Pd catalyst
      was obtained using the method and used for the semihydrogenation of 2-methyl-3
      butyn-2-ol providing 93 +/- 1.5% alkene yield for 100 h without deactivation.
      Although the coating method was applied only for TiO2 deposition, it is
      nonetheless suitable for the deposition of volatile sols. 

PMID- 25749620
TI  - PCDD/Fs in air and soil around an e-waste dismantling area with open burning of
      insulated wires in south China.
AB  - Polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs) in ambient air and
      farmland soil sampled in 2006 around an e-waste dismantling area with open
      burning of insulated wires in Longtang in south China were investigated. The
      total toxic equivalent concentrations of PCDD/Fs were 3.2-31.7 pg/m(3) in air and
      5.8 12.4 ng/kg in farmland soil at an e-waste site and 0.063-0.091 pg/m(3) in air
      at a background site. PCDD/Fs in the air at the e-waste site were characterized
      with dominant 1,2,3,4,6,7,8-HpCDF and OCDF and higher concentrations of furans
      than dioxins, suggesting open burning of insulated wires was likely to be the
      main source of PCDD/Fs. Compared with the results in this study, the level of
      PCDD/F tended to lessen with the average TEQ concentration decreasing by 41 % and
      the pattern changed to be dominated by OCDD in the air of Longtang in 2010 when
      insulated wires were openly burned in only a small scale. Our results indicate
      that the lower chlorinated congeners with higher vapor pressures have enhanced
      atmospheric transport tendencies.

PMID- 25749622
TI  - Who are coauthors and what should be their responsibilities?

PMID- 25749621
TI  - Polyploidisation and geographic differentiation drive diversification in a
      European High Mountain Plant Group (Doronicum clusii Aggregate, Asteraceae).
AB  - Range shifts (especially during the Pleistocene), polyploidisation and
      hybridization are major factors affecting high-mountain biodiversity. A good
      system to study their role in the European high mountains is the Doronicum clusii
      aggregate (Asteraceae), whose four taxa (D. clusii s.s., D. stiriacum, D.
      glaciale subsp. glaciale and D. glaciale subsp. calcareum) are differentiated
      geographically, ecologically (basiphilous versus silicicolous) and/or via their
      ploidy levels (diploid versus tetraploid). Here, we use DNA sequences (three
      plastid and one nuclear spacer) and AFLP fingerprinting data generated for 58
      populations to infer phylogenetic relationships, origin of polyploids-whose
      ploidy level was confirmed by chromosomally calibrated DNA ploidy level estimates
      and phylogeographic history. Taxonomic conclusions were informed, among others,
      by a Gaussian clustering method for species delimitation using dominant
      multilocus data. Based on molecular data we identified three lineages: (i)
      silicicolous diploid D. clusii s.s. in the Alps, (ii) silicicolous tetraploid D.
      stiriacum in the eastern Alps (outside the range of D. clusii s.s.) and the
      Carpathians and (iii) the basiphilous diploids D. glaciale subsp. glaciale
      (eastern Alps) and D. glaciale subsp. calcareum (northeastern Alps); each taxon
      was identified as distinct by the Gaussian clustering, but the separation of D.
      glaciale subsp. calcareum and D. glaciale subsp. glaciale was not stable,
      supporting their taxonomic treatment as subspecies. Carpathian and Alpine
      populations of D. stiriacum were genetically differentiated suggesting phases of
      vicariance, probably during the Pleistocene. The origin (autopolyploid versus
      allopolyploid) of D. stiriacum remained unclear. Doronicum glaciale subsp.
      calcareum was genetically and morphologically weakly separated from D. glaciale
      subsp. glaciale but exhibited significantly higher genetic diversity and rarity.
      This suggests that the more widespread D. glaciale subsp. glaciale originated
      from D. glaciale subsp. calcareum, which is restricted to a prominent Pleistocene
      refugium previously identified in other alpine plant species. 

PMID- 25749623
TI  - A study comparing videocapillaroscopy and dermoscopy in the assessment of
      nailfold capillaries in patients with systemic sclerosis-spectrum disorders.
AB  - OBJECTIVES: Nailfold videocapillaroscopy (NVC), the current gold standard for
      detection of capillary abnormalities suggestive of an SSc-spectrum disorder, is
      not widely available: a key question is whether lower-magnification, easy-to-use
      dermoscopy compares favourably. This is especially relevant given the inclusion
      of capillaroscopic abnormality within the 2013 classification criteria for SSc.
      Our objectives were to examine the ability to classify capillaries and to
      evaluate abnormality (severity), by both NVC and dermoscopy, to determine whether
      these differ between general and specialist rheumatologists, and to compare intra
      and interrater reliability of both techniques. METHODS: NVC and dermoscopy
      images were acquired from all 10 nailbeds of 32 subjects with a range of
      capillary abnormalities. Images were graded (using a web-based interface) on a 0
      3 scale of severity: normal (0), mildly (1), definitely (2) and grossly abnormal
      (3), and an unclassifiable category. Raters graded images from four subjects (40
      nailbeds) using each technique, with five repeated images to estimate intrarater
      reliability. RESULTS: Forty-eight rheumatologists from 12 countries participated
      in the study (22 generalists, 26 specialists). While most images could be graded
      by both techniques, more were graded by NVC (84% vs 70%) and were systematically
      scored higher by NVC (mean difference 0.43 between the ratings). Agreement
      between the techniques was moderate. Intra- and interrater reliability were
      comparable for the two techniques in the classifiability of images and the
      grading of severity. CONCLUSION: Our results suggest that dermoscopy is
      comparable to NVC, although NVC images were more likely to be classifiable and
      were graded more severely.

PMID- 25749624
TI  - Association of antidepressant treatment with emergency admission to medical units
      for patients 65 years or older.
AB  - INTRODUCTION: There is increasing evidence relating the presence of depression in
      seniors and the risk of hospital admission in medical departments from the
      Emergency Services. OBJECTIVE: To determine the impact of antidepressant
      treatment (ATD) as a protective factor for emergency hospitalization in older
      people. METHOD: All patients aged 65 and over who required urgent attention for
      medical reasons at the Emergency Department of the Corporacio Sanitaria i
      Universitaria Parc Tauli (Sabadell, Barcelona, Spain) for the period between
      January and October 2012 were included in the study. Sociodemographic variables,
      alcohol and tobacco use, medical history and psychopharmacological treatment were
      obtained. The necessary sample size was calculated and a simple randomization was
      performed. Subsequently, a descriptive statistical analysis and parametric tests
      were conducted. RESULTS: A total of 674 patients (53% women) were evaluated, with
      a mean age of 78.45 years, and 27.6% of the cases (71% women) were receiving ATD.
      Among the 333 admitted patients (50%), 83 individuals (24.6%) had previously
      received ATD; this contrasts with the 103 cases (30.6%) of prior ATD treatment
      among the patients who were not admitted. After comparative analysis, the
      relationship between previous use of ATD and being admitted to hospital was not
      statistically significant in our global sample. This relationship was only
      statistically significant among the group aged 75 and over (neg. sig. 0.012).
      CONCLUSIONS: In our study, ATD was associated with a decreased risk of hospital
      admission for urgent medical conditions in people aged 75 and over. Treating
      depression may protect the elderly against admission to the Emergency department
      and may potentially be a quality criterion in preventing complications in this
      population.

PMID- 25749625
TI  - Tumor shrinkage associated with whole-mount histopathologic techniques in oral
      tongue carcinoma.
AB  - Shrinkage artifact of tumor tissue from histologic processing has not been
      rigorously quantified, particularly where the entire tumor is represented in a
      whole-mount specimen. Fourteen patients underwent partial-glossectomy for oral
      tongue carcinoma (OTC). Specimens were embedded into agar, cut into 3 mm blocks
      and photographed (macroscopic image), prior to histopathologic processing.
      Histology slides were digitized. Contours were made of tumor on both image sets
      and area plotted against block position. Volume estimates were mathematically
      derived based on these plots. The tumors shrank in volume by 20.2% (p=0.0006) on
      average; shrinkage by area ranged for all image pairs 0-48%. Tumor volume>median
      was significant in absolute shrinkage (p=0.002) but not percent shrinkage
      (p=0.42). Age, gender, and T stage were independent of shrinkage. This data shows
      whole-mount techniques produce shrinkage artifact in OTC that varies between
      tumors and blocks in the same tumor. In order to account for shrinkage,
      measurement must be performed case-by-case.

PMID- 25749626
TI  - Pneumothorax-associated fibroblastic lesion in combination with localized pleural
      angiomatosis: A possible cause of juvenile spontaneous hemopneumothorax.
AB  - Spontaneous hemopneumothorax is an uncommon but potentially life-threatening
      condition, with a potential for a rapid ventilatory collapse and a large
      collection of hidden blood loss into the pleural cavity. Here, we report the
      first case in the literature on pneumothorax-associated fibroblastic lesion in
      combination with localized pleural angiomatosis in a 19-year-old Caucasian male,
      resulting in massive spontaneous hemopneumothorax and hypovolemic shock. Our
      findings support a causal link between this condition and pneumothorax. The
      possible superimposed hemothorax is explainable by the pleural involvement of
      large angiomatous vessels, prone to rupture. 

PMID- 25749627
TI  - Penile pseudomyogenic hemangioendothelioma/epithelioid sarcoma-like
      hemangioendothelioma with a novel pattern of SERPINE1-FOSB fusion detected by RT
      PCR--report of a case.
AB  - We experienced a rare case of penile mesenchymal tumor in a 43-year-old Japanese
      man. At least three nodules were observed around the penis. The tumors were
      composed of spindle- to oval-shaped atypical cells with and without prominent
      nucleoli. These cells were like myogenic cells, but negative for myogenic
      markers. They were positive for endothelial markers, such as ERG, Fli1 and CD31.
      They were also positive for nuclear and cytoplasmic FOSB which are not expressed
      in epithelioid hemangioendothelioma or epithelioid sarcoma. These pathological
      and immunohistochemical findings strongly suggested pseudomyogenic
      hemangioendothelioma/epithelioid sarcoma-like hemangioendothelioma (PHE/ES-HE).
      Since a recent report directly proved that two cases of PHE/ES-HE have SERPINE1
      FOSB fusion gene by reverse transcription-polymerase chain reaction (RT-PCR), we
      examined whether the fusion gene is present or not in the present case by RT-PCR
      using fresh frozen surgical material. Sequencing of the PCR product revealed that
      this case has SERPINE1-FOSB fusion. The fusion pattern of our case was different
      from those of two previously reported cases. In our case, 86 nucleotides of
      SERPINE1 intron 1 were inserted between SERPINE1 exon 1 and the middle portion of
      FOSB exon 1, and a putative translation start codon was identified in SERPINE1
      intron 1. Thus, this is the third case of PHE/ES-HE with SERPINE1-FOSB fusion
      proved by RT-PCR. 

PMID- 25749628
TI  - [Primary infection and pulmonary tuberculosis].
AB  - Tuberculosis is a major public health problem worldwide. Indeed, a third of the
      world population is infected with Mycobacterium tuberculosis and more than 8
      million new cases of tuberculosis each year. Pulmonary tuberculosis is the most
      common location. Its diagnosis is difficult and often established with a delay
      causing a spread of infection. The diagnosis of tuberculosis infection is mainly
      based on immunological tests represented by the tuberculin skin test and
      detection of gamma interferon, while the diagnosis of pulmonary tuberculosis is
      suspected on epidemiological context, lasting general and respiratory symptoms,
      contrasting usually with normal lung examination, and a chest radiography showing
      suggestive lesions. The radioclinical feature may be atypical in patients with
      extreme ages and in case of immunodeficiency. Confirmation of tuberculosis is
      bacteriological. Conventional bacteriological methods remain the reference.
      Innovative tests using the technique of molecular biology have improved the
      diagnosis of tuberculosis in terms of sensitivity and especially speed. However,
      those techniques are of limited use.

PMID- 25749632
TI  - Perphenazine for schizophrenia.
AB  - BACKGROUND: Perphenazine is an old phenothiazine antipsychotic with a potency
      similar to haloperidol. It has been used for many years and is popular in the
      northern European countries and Japan. OBJECTIVES: To examine the clinical
      effects and safety of perphenazine for those with schizophrenia and schizophrenia
      like psychoses. SEARCH METHODS: We updated our original search using the Cochrane
      Schizophrenia Group's register (September 2013), references of all included
      studies and contacted pharmaceutical companies and authors of included studies in
      order to identify further trials. SELECTION CRITERIA: We included all randomised
      controlled trials that compared perphenazine with other treatments for people
      with schizophrenia and/or schizophrenia-like psychoses. We excluded trials of
      depot formulations of perphenazine. DATA COLLECTION AND ANALYSIS: Two review
      authors independently inspected citations and, where possible, abstracts. We
      ordered papers, inspected and quality assessed them. We extracted data, again
      working independently. If loss to follow-up was greater than 50% we considered
      results as 'prone to bias'. For dichotomous data, we calculated risk ratios (RR)
      and for continuous data we calculated mean differences (MD), both with the 95%
      confidence intervals (CI). We assessed quality of data using the GRADE (Grading
      of Recommendations Assessment, Development and Evaluationtool) and assessed risk
      of bias for included studies. MAIN RESULTS: Thirty-one studies fulfilled the
      inclusion criteria, with a total of 4662 participants (of which 4522 were
      receiving the drugs relevant to our comparison) and presented data that could be
      used for at least one comparison. The trial centres were located in Europe
      (especially Scandinavia), Japan and Northern America.When comparing perphenazine
      with placebo, for our primary outcome of clinical response, results favoured
      perphenazine with significantly more people receiving placebo rated as either 'no
      better or deterioration' for global state than people receiving perphenazine (1
      RCT, n = 61 RR 0.32 CI 0.13 to 0.78, very low quality evidence). More people
      receiving placebo relapsed, although not a statistically significant number (1
      RCT, n = 48, RR 0.14 CI 0.02 to 1.07, very low quality evidence). Death was not
      reported in the perphenazine versus placebo comparison. Experiences of dystonia
      were equivocal between groups (1 RCT, n = 48, RR 1.00 CI 0.07 to 15.08, very low
      quality evidence); other outcomes not reported in this comparison include serious
      adverse events, economic outcomes, and service use and hospitalisation.For the
      comparison of perphenazine versus any other antipsychotic drugs, no real
      differences in effect between the drugs were found. There was no significant
      difference between groups for those considered 'no better or deterioration' (17
      RCTs, n = 1879, RR 1.04 CI 0.91 to 1.17, very low quality evidence). For mental
      state outcome of 'no effect' of the study drug, there was again no significant
      difference between groups (4 RCTs, n = 383, RR 1.24 CI 0.61 to 2.52, very low
      quality evidence). Death was not reported in any of the included studies. There
      was no significant difference in rates of dystonia with perphenazine versus any
      other antipsychotic drugs (4 RCTs, n = 416, RR 1.36 CI 0.23 to 8.16, very low
      quality evidence), nor was there a significant difference between groups for
      serious adverse events (2 RCTs, n = 1760, RR 0.98 CI 0.68 to 1.41, very low
      quality evidence). AUTHORS' CONCLUSIONS: Although perphenazine has been used in
      randomised trials for more than 50 years, incomplete reporting and the variety of
      comparators used make it impossible to draw clear conclusions. All data for the
      main outcomes in this review were of very low quality evidence. At best we can
      say that perphenazine showed similar effects and adverse events as several of the
      other antipsychotic drugs. Since perphenazine is a relatively inexpensive and
      frequently used compound, further trials are justified to clarify the properties
      of this classical antipsychotic drug.

PMID- 25749630
TI  - Preferred features of oral treatments and predictors of non-adherence: two web
      based choice experiments in multiple sclerosis patients.
AB  - BACKGROUND: Oral disease modifying therapies (DMTs) for multiple sclerosis (MS)
      differ in efficacy, tolerability, and safety. OBJECTIVE: We sought to understand
      how these attributes impact patient preference and predicted DMT non-adherence
      among oral-naive MS patients. METHODS: Adult MS patients from the
      "PatientsLikeMe" Web-based health data-sharing platform completed a discrete
      choice exercise where they were asked to express their preference for one of
      three hypothetical oral DMTs, each with a certain combination of levels of tested
      attributes. Another Web-based exercise tested a number of possible drivers of non
      adherence, mainly side effects. Data from an MS clinic were used to adjust for
      sample bias. Respondents' preferences were analyzed using Hierarchical Bayesian
      estimation. RESULTS: A total of 319 patients completed all questions. Most
      respondents were female (77.7%, 248/319) with mean age 48 years (SD 10). Liver
      toxicity was the attribute that emerged as the most important driver of patient
      preference (25.8%, relative importance out of 100%), followed by severe side
      effects (15.3%), delay to disability progression (10.7%), and common side effects
      (10.4%). The most important drivers of predicted non-adherence were frequency of
      daily dosing (17.4% out of 100%), hair thinning (14.8%), use during pregnancy
      (14.1%), severe side effects (13.8%), and diarrhea (13.0%). CONCLUSIONS:
      Understanding the important concerns expressed by patients may help health care
      providers to understand and educate their patients more completely about these
      concerns. This knowledge may therefore improve both choices of appropriate
      therapy and adherence to therapy over time.

PMID- 25749634
TI  - Concurrent correlates of Chinese word recognition in deaf and hard-of-hearing
      children.
AB  - The aim of this study was to explore the relative contributions of phonological,
      semantic radical, and morphological awareness to Chinese word recognition in deaf
      and hard-of-hearing (DHH) children. Measures of word recognition, general
      intelligence, phonological, semantic radical, and morphological awareness were
      administered to 32 DHH and 35 hearing children in Hong Kong. Hierarchical
      regression analyses showed that tone, semantic radical, and morphological
      awareness made independent contributions to word recognition in DHH children
      after the effects of age and intelligence were statistically controlled for.
      Semantic radical and morphological awareness was found to explain significantly
      more variance than tone awareness in predicting word recognition in DHH children.
      This study has replicated previous evidence regarding the importance of semantic
      radical and morphological awareness in Chinese word recognition in hearing
      children and extended its significance to DHH children. 

PMID- 25749635
TI  - Photo-catalytic activities of plant hormones on semiconductor nanoparticles by
      laser-activated electron tunneling and emitting.
AB  - Understanding of the dynamic process of laser-induced ultrafast electron
      tunneling is still very limited. It has been thought that the photo-catalytic
      reaction of adsorbents on the surface is either dependent on the number of
      resultant electron-hole pairs where excess energy is lost to the lattice through
      coupling with phonon modes, or dependent on irradiation photon wavelength. We
      used UV (355 nm) laser pulses to excite electrons from the valence band to the
      conduction band of titanium dioxide (TiO2), zinc oxide (ZnO) and bismuth cobalt
      zinc oxide (Bi2O3)0.07(CoO)0.03(ZnO)0.9 semiconductor nanoparticles with
      different photo catalytic properties. Photoelectrons are extracted, accelerated
      in a static electric field and eventually captured by charge deficient atoms of
      adsorbed organic molecules. A time-of-flight mass spectrometer was used to detect
      negative molecules and fragment ions generated by un-paired electron directed
      bond cleavages. We show that the probability of electron tunneling is determined
      by the strength of the static electric field and intrinsic electron mobility of
      semiconductors. Photo-catalytic dissociation or polymerization reactions of
      adsorbents are highly dependent on the kinetic energy of tunneling electrons as
      well as the strength of laser influx. By using this approach, photo-activities of
      phytohormones have been investigated.

PMID- 25749636
TI  - A survey of cyclic and linear siloxanes in indoor dust and their implications for
      human exposures in twelve countries.
AB  - Siloxanes are used widely in a variety of consumer products, including cosmetics,
      personal care products, medical and electrical devices, cookware, and building
      materials. Nevertheless, little is known on the occurrence of siloxanes in indoor
      dust. In this survey, five cyclic (D3-D7) and 11 linear (L4-L14) siloxanes were
      determined in 310 indoor dust samples collected from 12 countries. Dust samples
      collected from Greece contained the highest concentrations of total cyclic
      siloxanes (TCSi), ranging from 118 to 25,100ng/g (median: 1380), and total linear
      siloxanes (TLSi), ranging from 129 to 4990ng/g (median: 772). The median total
      siloxane (TSi) concentrations in dust samples from 12 countries were in the
      following decreasing order: Greece (2970ng/g), Kuwait (2400), South Korea (1810),
      Japan (1500), the USA (1220), China (1070), Romania (538), Colombia (230),
      Vietnam (206), Saudi Arabia (132), India (116), and Pakistan (68.3). TLSi
      concentrations as high as 42,800ng/g (Kuwait) and TCSi concentrations as high as
      25,000ng/g (Greece) were found in indoor dust samples. Among the 16 siloxanes
      determined, decamethylcyclopentasiloxane (D5) was found at the highest
      concentration in dust samples from all countries, except for Japan and South
      Korea, with a predominance of L11; Kuwait, with L10; and Pakistan and Romania,
      with L12. The composition profiles of 16 siloxanes in dust samples varied by
      country. TCSi accounted for a major proportion of TSi concentrations in dust
      collected from Colombia (90%), India (80%) and Saudi Arabia (70%), whereas TLSi
      predominated in samples collected from Japan (89%), Kuwait (85%), and South Korea
      (78%). Based on the measured median TSi concentrations in indoor dust, we
      estimated human exposure doses through indoor dust ingestion for various age
      groups. The exposure doses ranged from 0.27 to 11.9ng/kg-bw/d for toddlers and
      0.06 to 2.48ng/kg-bw/d for adults.

PMID- 25749629
TI  - RIG-I in RNA virus recognition.
AB  - Antiviral immunity is initiated upon host recognition of viral products via non
      self molecular patterns known as pathogen-associated molecular patterns (PAMPs).
      Such recognition initiates signaling cascades that induce intracellular innate
      immune defenses and an inflammatory response that facilitates development of the
      acquired immune response. The retinoic acid-inducible gene I (RIG-I) and the RIG
      I-like receptor (RLR) protein family are key cytoplasmic pathogen recognition
      receptors that are implicated in the recognition of viruses across genera and
      virus families, including functioning as major sensors of RNA viruses, and
      promoting recognition of some DNA viruses. RIG-I, the charter member of the RLR
      family, is activated upon binding to PAMP RNA. Activated RIG-I signals by
      interacting with the adapter protein MAVS leading to a signaling cascade that
      activates the transcription factors IRF3 and NF-kappaB. These actions induce the
      expression of antiviral gene products and the production of type I and III
      interferons that lead to an antiviral state in the infected cell and surrounding
      tissue. RIG-I signaling is essential for the control of infection by many RNA
      viruses. Recently, RIG-I crosstalk with other pathogen recognition receptors and
      components of the inflammasome has been described. In this review, we discuss the
      current knowledge regarding the role of RIG-I in recognition of a variety of
      virus families and its role in programming the adaptive immune response through
      cross-talk with parallel arms of the innate immune system, including how RIG-I
      can be leveraged for antiviral therapy. 

PMID- 25749637
TI  - Accumulation of 19 environmental phenolic and xenobiotic heterocyclic aromatic
      compounds in human adipose tissue.
AB  - The extensive use of environmental phenols (e.g., bisphenol A) and heterocyclic
      aromatic compounds (e.g., benzothiazole) in consumer products as well as
      widespread exposure of humans to these compounds have been well documented.
      Biomonitoring studies have used urinary measurements to assess exposures, based
      on the assumption that these chemicals are metabolized and eliminated in urine.
      Despite the fact that some of these chemicals are moderately lipophilic, the
      extent of their accumulation in adipose fat tissues has not been convincingly
      demonstrated. In this study, human adipose fat samples (N=20) collected from New
      York City, USA, were analyzed for the presence of environmental phenols,
      including bisphenol A (BPA), benzophenone-3 (BP-3), triclosan (TCS), and
      parabens, as well as heterocyclic aromatic compounds, including benzotriazole
      (BTR), benzothiazole (BTH), and their derivatives. BPA and TCS were frequently
      detected in adipose tissues at concentrations (geometric mean [GM]: 3.95ng/g wet
      wt for BPA and 7.21ng/g wet wt for TCS) similar to or below the values reported
      for human urine. High concentrations of BP-3 were found in human adipose tissues
      (GM: 43.4; maximum: 4940ng/g wet wt) and a positive correlation between BP-3
      concentrations and donor's age was observed. The metabolite of parabens, p
      hydroxybenzoic acid (p-HB), also was found at elevated levels (GM: 4160; max.:
      17,400ng/g wet wt) and a positive correlation between donor's age and sum
      concentration of parabens and p-HB were found. The GM concentrations of BTR and
      BTH in human adipose tissues were below 1ng/g, although the methylated forms of
      BTR (i.e., TTR and XTR) and the hydrated form of BTH (i.e., 2-OH-BTH) were
      frequently detected in adipose samples, indicating widespread exposure to these
      compounds. Our results suggest that adipose tissue is an important repository for
      BP-3 and parabens, including p-HB, in the human body.

PMID- 25749638
TI  - Dry-contact microelectrode membranes for wireless detection of electrical
      phenotypes in neonatal mouse hearts.
AB  - Continuous monitoring of aberrant electrical rhythms during heart injury and
      repair requires prolonged data acquisition. We hereby developed a wearable
      microelectrode membrane that could be adherent to the chest of neonatal mice for
      in situ wireless recording of electrocardiogram (ECG) signals. The novel dry
      contact membrane with a meshed parylene-C pad adjacent to the microelectrodes and
      the expandable meandrous strips allowed for varying size of the neonates. The
      performance was evaluated at the system level; specifically, the ECG signals
      (MUV) acquired from the microelectrodes underwent two-stage amplification, band
      pass filtering, and optical data transmission by an infrared Light Emitting Diode
      (LED) to the data-receiving unit. The circuitry was prototyped on a printed
      circuit board (PCB), consuming less than 300 MUW, and was completely powered by
      an inductive coupling link. Distinct P waves, QRS complexes, and T waves of ECG
      signals were demonstrated from the non-pharmacologically sedated neonates at ~600
      beats per minutes. Thus, we demonstrate the feasibility of both real-time and
      wireless monitoring cardiac rhythms in a neonatal mouse (17-20 mm and <1 g) via
      dry-contact microelectrode membrane; thus, providing a basis for diagnosing
      aberrant electrical conduction in animal models of cardiac injury and repair. 

PMID- 25749640
TI  - Highly efficient capture and harvest of circulating tumor cells on a microfluidic
      chip integrated with herringbone and micropost arrays.
AB  - Circulating tumor cells (CTCs), which are derived from primary tumor site and
      transported to distant organs, are considered as the major cause of metastasis.
      So far, various techniques have been applied for CTC isolation and enumeration.
      However, there exists great demand to improve the sensitivity of CTC capture, and
      it remains challenging to elute the cells efficiently from device for further
      biomolecular and cellular analyses. In this study, we fabricate a dual functional
      chip integrated with herringbone structure and micropost array to achieve CTC
      capture and elution through EpCAM-based immunoreaction. Hep3B tumor cell line is
      selected as the model of CTCs for processing using this device. The results
      demonstrate that the capture limit of Hep3B cells can reach up to 10 cells (per
      mL of sample volume) with capture efficiency of 80% on average. Moreover, the
      elution rate of the captured Hep3B cells can reach up to 69.4% on average for
      cell number ranging from 1 to 100. These results demonstrate that this device
      exhibits dual functions with considerably high capture rate and elution rate,
      indicating its promising capability for cancer diagnosis and therapeutics.

PMID- 25749639
TI  - Development and characterization of hollow microprobe array as a potential tool
      for versatile and massively parallel manipulation of single cells.
AB  - Parallel manipulation of single cells is important for reconstructing in vivo
      cellular microenvironments and studying cell functions. To manipulate single
      cells and reconstruct their environments, development of a versatile manipulation
      tool is necessary. In this study, we developed an array of hollow probes using
      microelectromechanical systems fabrication technology and demonstrated the
      manipulation of single cells. We conducted a cell aspiration experiment with a
      glass pipette and modeled a cell using a standard linear solid model, which
      provided information for designing hollow stepped probes for minimally invasive
      single-cell manipulation. We etched a silicon wafer on both sides and formed
      through holes with stepped structures. The inner diameters of the holes were
      reduced by SiO2 deposition of plasma-enhanced chemical vapor deposition to trap
      cells on the tips. This fabrication process makes it possible to control the wall
      thickness, inner diameter, and outer diameter of the probes. With the fabricated
      probes, single cells were manipulated and placed in microwells at a single-cell
      level in a parallel manner. We studied the capture, release, and survival rates
      of cells at different suction and release pressures and found that the cell
      trapping rate was directly proportional to the suction pressure, whereas the
      release rate and viability decreased with increasing the suction pressure. The
      proposed manipulation system makes it possible to place cells in a well array and
      observe the adherence, spreading, culture, and death of the cells. This system
      has potential as a tool for massively parallel manipulation and for three
      dimensional hetero cellular assays. 

PMID- 25749642
TI  - The Theory of Everything and a neglected tropical disease: a Hawking legacy.

PMID- 25749641
TI  - Effects of exercise intensity compared to albuterol in individuals with cystic
      fibrosis.
AB  - BACKGROUND: Although exercise is a vital component of the therapy prescribed to
      individuals with cystic fibrosis (CF), it is not a priority due to a finite
      amount of treatment time and the view that exercise is not as beneficial as
      pharmacological treatments by many individuals with CF. We sought to compare the
      therapeutic benefits of exercise and their prescribed bronchodilator albuterol.
      METHODS: CF (n = 14) and healthy (n = 16) subjects completed three visits, a
      baseline screening with VO2 max test and two treatment visits. On the two
      treatment visits, subjects completed spirometry and diffusing capacity of the
      lungs for nitric oxide (DLNO) maneuvers either at baseline, 60, and 110 min post
      albuterol administration, or at baseline and the midway point of three separate
      15 min exercise bouts at low, moderate and vigorous intensity (25, 50 and 65% of
      the maximum workload, respectively). RESULTS: With moderate exercise the increase
      in DLNO was double (39 +/- 8 vs 15  +/- 6% change) and the level of
      bronchodilation similar (23% change) when compared to 110 min post-albuterol in
      individuals with CF. During exercise FVC became reduced (-309 +/- 66 mL with
      moderate exercise) and the increase in FEV1 was attenuated (103 +/- 39 vs 236 +/-
      58 mL, exercise vs. albuterol) when compared with the response to albuterol in
      individuals with CF. Epinephrine (EPI) release increased 39, 72 and 144% change
      with low, moderate and vigorous intensity exercise respectively for individuals
      with CF, but this increase was blunted when compared to healthy subjects.
      CONCLUSION: Our results suggest that moderate intensity exercise is the optimal
      intensity for individuals with CF, as low intensity exercise increases EPI less
      than 50% and vigorous intensity exercise is over taxing, such that airflow can be
      restricted. Although the duration of the beneficial effect is uncertain, exercise
      can promote greater improvements in gas diffusion and comparable bronchodilation
      when compared to albuterol.

PMID- 25749643
TI  - Black pleural effusion.

PMID- 25749644
TI  - Digoxin use in patients with atrial fibrillation and adverse cardiovascular
      outcomes: a retrospective analysis of the Rivaroxaban Once Daily Oral Direct
      Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke
      and Embolism Trial in Atrial Fibrillation (ROCKET AF).
AB  - BACKGROUND: Digoxin is a widely used drug for ventricular rate control in
      patients with atrial fibrillation (AF), despite a scarcity of randomised trial
      data. We studied the use and outcomes of digoxin in patients in the Rivaroxaban
      Once Daily Oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonism
      for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET AF).
      METHODS: For this retrospective analysis, we included and classified patients
      from ROCKET AF on the basis of digoxin use at baseline and during the study.
      Patients in ROCKET AF were recruited from 45 countries and had AF and risk
      factors putting them at moderate-to-high risk of stroke, with or without heart
      failure. We used Cox proportional hazards regression models adjusted for baseline
      characteristics and drugs to investigate the association of digoxin with all
      cause mortality, vascular death, and sudden death. ROCKET AF was registered with
      ClinicalTrials.gov, number NCT00403767. FINDINGS: In 14,171 randomly assigned
      patients, digoxin was used at baseline in 5239 (37%). Patients given digoxin were
      more likely to be female (42% vs 38%) and have a history of heart failure (73% vs
      56%), diabetes (43% vs 38%), and persistent AF (88% vs 77%; p<0.0001 for each
      comparison). After adjustment, digoxin was associated with increased all-cause
      mortality (5.41 vs 4.30 events per 100 patients-years; hazard ratio 1.17; 95% CI
      1.04-1.32; p=0.0093), vascular death (3.55 vs 2.69 per 100 patient-years; 1.19;
      1.03-1.39, p=0.0201), and sudden death (1.68 vs 1.12 events per 100 patient
      years; 1.36; 1.08-1.70, p=0.0076). INTERPRETATION: Digoxin treatment was
      associated with a significant increase in all-cause mortality, vascular death,
      and sudden death in patients with AF. This association was independent of other
      measured prognostic factors, and although residual confounding could account for
      these results, these data show the possibility of digoxin having these effects. A
      randomised trial of digoxin in treatment of AF patients with and without heart
      failure is needed. FUNDING: Janssen Research & Development and Bayer HealthCare
      AG.

PMID- 25749645
TI  - Digoxin use in atrial fibrillation: a critical reappraisal.

PMID- 25749647
TI  - Impulsivity in bipolar and substance use disorders.
AB  - BACKGROUND: Bipolar disorder (BD) is commonly associated with increased
      impulsivity, particularly during manic and depressed episodes; also impulsivity
      remains elevated during euthymic phases. Impulsivity is also a factor in the
      initiation and maintenance of substance use disorders (SUD). Impulsivity can
      predispose to substance abuse or can result from it. Impulsivity appears to be
      relatively independent of mood state and is higher in individuals with past
      substance use. Thus, we wanted to compare the impulsivity of BD and SUD closely
      associated with impulsivity and identify potential differences. METHODS:
      Impulsivity was evaluated by the Barratt Impulsiveness Scale (BIS-11A), in 35
      bipolar interepisode disorder male patients without comorbid substance use
      disorder and 40 substance use disorder male patients. The BIS-11A mean scores for
      the two groups were compared through one-way between-groups ANOVA. RESULTS: There
      was no difference between the BD and substance use disorder groups on total and
      subscale attentional, motor impulsivity measures. However, for the male patients
      there was difference on the nonplanning subscale. The male BD patient group
      scored higher than the male substance use disorder patient group regarding
      nonplanning impulsivity. CONCLUSIONS: Our results replicate the findings that
      interepisode BD and substance use disorder patients both have increased total
      impulsivity; furthermore, the findings also indicate that trait impulsivity is
      not completely the same in subscales. Both groups were similar on attention and
      motor impulsivity subscales; however, on the nonplanning subscale, BD patients
      were more impulsive than the substance use disorder patients.

PMID- 25749646
TI  - Increased Sensitivity to Cocaine Self-Administration in HIV-1 Transgenic Rats is
      Associated with Changes in Striatal Dopamine Transporter Binding.
AB  - Cocaine abuse in HIV patients accelerates the progression and severity of
      neuropathology, motor impairment and cognitive dysfunction compared to non-drug
      using HIV patients. Cocaine and HIV interact with the dopamine transporter (DAT);
      however, the effect of their interaction on DAT binding remains understudied. The
      present study compared the dose-response functions for intravenous self
      administration of cocaine and heroin between male HIV-1 transgenic (HIV-1 Tg) and
      Fischer 344 rats. The cocaine and heroin dose-response functions exhibit an
      inverted U-shape for both HIV-1 Tg and F344 rats. For cocaine, the number of
      infusions for each dose on the ascending limb was greater for HIV-1 Tg versus
      F344 rats. No significant changes in the heroin dose-response function were
      observed in HIV-1 Tg animals. Following the conclusion of self-administration
      experiments, DAT binding was assessed in striatal membranes. Saturation binding
      of the cocaine analog [(125)I] 3beta-(4-iodophenyl)tropan-2beta-carboxylic acid
      methyl ester ([(125)I]RTI-55) in rat striatal membranes resulted in binding
      curves that were best fit to a two-site binding model, allowing for calculation
      of dissociation constant (Kd) and binding density (Bmax) values that correspond
      to high- and low-affinity DAT binding sites. Control HIV-1 Tg rats exhibited a
      significantly greater affinity (i.e., decrease in Kd value) in the low-affinity
      DAT binding site compared to control F344 rats. Furthermore, cocaine self
      administration in HIV-1 Tg rats increased low-affinity Kd (i.e., decreased
      affinity) compared to levels observed in control F344 rats. Cocaine also
      increased low-affinity Bmax in HIV-1 Tg rats as compared to controls, indicating
      an increase in the number of low-affinity DAT binding sites. F344 rats did not
      exhibit any change in high- or low-affinity Kd or Bmax values following cocaine
      or heroin self-administration. The increase in DAT affinity in cocaine HIV-1 Tg
      rats is consistent with the leftward shift of the ascending limb of the cocaine
      dose-response curve observed in HIV-1 Tg vs. F344 rats, and has major
      implications for the function of cocaine binding to DAT in HIV patients. The
      absence of HIV-related changes in heroin intake are likely due to less
      dopaminergic involvement in the mediation of heroin reward, further emphasizing
      the preferential influence of HIV on dopamine-related behaviors. 

PMID- 25749648
TI  - The association of serotype and pulsed-field gel electrophoresis genotype in
      isolates of Streptococcus pneumoniae isolated in Israel.
AB  - The relationship between Streptococcus pneumoniae isolates causing invasive
      infections in children admitted to a single center in central Israel was examined
      by pulsed-field gel electrophoresis (PFGE) and serotyping. Although there was a
      close correlation between serotype and PFGE clone, the genetic diversity varied
      by serotype, with some genotypes comprising multiple serotypes. Additionally,
      clones C and D were associated with higher penicillin minimum inhibitory
      concentrations. Serotyping alone may be insufficient for epidemiological mapping
      of pneumococcal isolates in the era of pneumococcal conjugate polysaccharide
      vaccines. 

PMID- 25749649
TI  - Comparative evaluation of the new xTAG GPP multiplex assay in the laboratory
      diagnosis of acute gastroenteritis. Clinical assessment and potential application
      from a multicentre Italian study.
AB  - OBJECTIVE: Gastroenteritis caused by a single pathogen or multiple pathogens
      remains a major diagnostic challenge for the laboratory. The treatment of
      diarrhoea is based on microbiological results. Diagnosis is achieved using
      different laboratory techniques that have variable sensitivity and specificity.
      xTAG GPP is a new multiplex PCR assay that simultaneously detects 15 different
      pathogens responsible for diarrhoea. The results of the first multicentre study
      in Italy to evaluate the potential clinical application of the GPP assay in the
      laboratory diagnosis of diarrhoea are reported here. METHODS: Faeces specimens
      (N=664) from hospitalized patients were tested with the GPP assay using a Luminex
      200 instrument. All specimens were run using comparator methods following a
      routine algorithm: culture for bacteria, enzyme immunoassay and PCR for viruses,
      and microscopy for parasites. RESULTS: Of the samples tested with the GPP, 53.61%
      (356/664) gave positive results, as compared to 45.33% by routine testing. Of the
      positive specimens, 34.55% showed the presence of genomic DNA from multiple
      pathogens. The Luminex method showed an increase in the percentage of positivity
      of 8.28%. CONCLUSIONS: The GPP assay can be considered a helpful tool for the
      detection of gastrointestinal pathogens, with a hands-on time of 5h; it provides
      accurate data for the clinical management of hospitalized patients and for
      epidemiological surveillance.

PMID- 25749650
TI  - Understanding hermaphrodite species through game theory.
AB  - We investigate the existence and stability of sexual strategies (sequential
      hermaphrodite, successive hermaphrodite or gonochore) at a proximate level. To
      accomplish this, we constructed and analyzed a general dynamical game model
      structured by size and sex. Our main objective is to study how costs of changing
      sex and of sexual competition should shape the sexual behavior of a
      hermaphrodite. We prove that, at the proximate level, size alone is insufficient
      to explain the tendency for a pair of prospective copulants to elect the male
      sexual role by virtue of the disparity in the energetic costs of eggs and sperm.
      In fact, we show that the stability of sequential vs. simultaneous hermaphrodite
      depends on sex change costs, while the stability of protandrous vs. protogynous
      strategies depends on competition cost. 

PMID- 25749651
TI  - Recalled Initiation and Duration of Maternal Breastfeeding Among Children with
      and Without ADHD in a Well Characterized Case-Control Sample.
AB  - Early environmental influences are increasingly of interest in understanding ADHD
      as a neurodevelopmental condition, particularly in light of recognition that gene
      by environment interplay are likely involved in this condition. Breastfeeding
      duration predicts cognitive development, as well as development of brain white
      matter connectivity, in areas similar to those seen in ADHD. Prior studies show
      an association between breastfeeding and ADHD but without adequate evaluation of
      ADHD. A case control cohort of 474 children aged 7-13 years was examined, 291
      with well characterized ADHD (71.5 % male) and the rest typically developing
      controls (51.9 % male). Mothers retrospectively reported on breast feeding
      initiation and duration. Initiation of breastfeeding was not associated with
      child ADHD, but shorter duration of breastfeeding was associated with child ADHD
      with a medium effect size (d = 0.40, p < 0.05); this effect held after covarying
      a broad set of potential confounders, including child oppositional defiant and
      conduct problems and including maternal and paternal ADHD symptoms. Effects were
      replicated across both parent and teacher ratings of child ADHD symptoms. Shorter
      duration of breastfeeding is among several risk factors in early life associated
      with future ADHD, or else longer duration is protective. The direction of this
      effect is unknown, however. It may be that some children are more difficult to
      breastfeed or that breastfeeding provides nutrients or other benefits that reduce
      future chance of ADHD.

PMID- 25749652
TI  - Novel inhibitor discovery and the conformational analysis of inhibitors of
      listeriolysin O via protein-ligand modeling.
AB  - Increasing bacterial resistance to available antibiotics makes the discovery of
      novel efficacious antibacterial agents a priority. A previous report showed that
      listeriolysin O (LLO) is a critical virulence factor and suggested that it is a
      target for developing anti-virulence drugs against Listeria monocytogenes
      infections. In this study, we report the discovery of LLO natural compound
      inhibitors with differential activity by using hemolysis assay. The mechanism of
      action of the inhibitors was consistent with that of fisetin, a natural flavonoid
      without antimicrobial activity, which we showed in our previous report via
      molecular simulation. Furthermore, a substantial increase in anti-hemolytic
      activity was observed when the single bond (C1-C2) was replaced by a double bond
      (C1-C2) in the inhibitor molecule. This change was based on the decomposition of
      the ligand-residue interaction, which indicated that the double bond (C1-C2) in
      the inhibitors was required for their inhibition of LLO. The current MD
      simulation work provides insights into the mechanism by which the compounds
      inhibit LLO at the atomic level and will be useful for the development of new,
      selective LLO inhibitors. 

PMID- 25749653
TI  - Quantitative analysis of the patella following the harvest of a quadriceps tendon
      autograft with a bone block.
AB  - PURPOSE: The objective of this study was to determine parameters associated with
      patellar fracture after quadriceps tendon autograft harvest. METHODS: Thirteen
      non-fractured and five fractured patella surface models were created based on
      patient data obtained from a prospective randomized clinical trial in order to
      assess geometric parameters and bending stress. Measurements that describe the
      bone block harvest site geometry were used to calculate three normalized
      parameters. The relative depth parameter describes the thickness of the bone
      block harvest site with respect to the thickness of the patella at the harvest
      site. The asymmetry parameter defines the medial-lateral location of the bone
      bock harvest site. The normalized bending stress parameter assesses the bending
      stress experienced by the remaining bone beneath the bone block harvest site.
      RESULTS: The relative depth of the bone block harvest site in the non-fractured
      patellae was 27 +/- 12 % and for the fractured patellae was 42 +/- 14 % (p <
      0.05). With a value <1 indicating a more lateral location of the harvest site,
      asymmetry for the non-fractured group was 1.0 +/- 0.5 and 0.7 +/- 0.4 for the
      fractured group (n.s.). The maximum bending stress experienced by the non
      fractured patellae was (1.8 * 10(-3) +/- 1.3 * 10(-3)) mm(-3) * M and for the
      fractured patellae was over three times greater (6.3 * 10(-3) +/- 3.7 * 10(-3))
      mm(-3) * M (p < 0.05). CONCLUSION: Based on the non-uniform geometry of the
      patella, an emphasis should be made on harvesting a standard percentage of
      patella thickness rather than a fixed depth. In order to minimize the incidence
      of a patellar fracture, bone blocks should not be taken laterally and should not
      exceed 30 % of the total patella thickness at the harvest site.

PMID- 25749654
TI  - Biomechanical evaluation contribution of the acetabular labrum to hip stability.
AB  - PURPOSE: Knowledge of the effect of hip pathologies on hip biomechanics is
      important to the understanding of the development of osteoarthritis, and the
      contribution of the labrum to hip joint stability has had limited study. The
      purpose of this study was to evaluate the effect of labral injury to stability of
      the femoral head in the acetabular socket. METHODS: Ten cadaver hip specimens
      were tested using a robotic system under four different loading conditions: axial
      loading (80 N) along the femoral axis and axial loading (80 N) combined with
      either anterior, posterior or lateral loading (60 N). The hip states were
      examined were intact, with a 1.5 cm capsulotomy and with a 1 cm resection of the
      anterosuperior labrum. RESULTS: At 30 degrees  of flexion, under axial load, the
      displacement of the hip with capsulotomy and labral resection (9.6 +/- 2.5 mm)
      was significantly larger then the hip with capsulotomy alone (5.6 +/- 4.1 mm, p =
      0.005) and the intact hip (5.2 +/- 3.8 mm, p = 0.005). Also, at 30 degrees  of
      flexion, the displacement under combined axial and anterior/posterior load was
      increased with capsulotomy and labral resection. CONCLUSION: The acetabular
      labrum provides stability to the hip joint in response to a distraction force and
      combined distraction and translation forces. One centimetre of labral resection
      caused significant displacement ("wobbling" effect) of the femoral head within
      the acetabulum with normal range of motion. Successful labral repair could be
      crucial for restoration of the hip biomechanics and prevention of coxarthrosis.

PMID- 25749655
TI  - Erratum to: Functional assessments for decision-making regarding return to sports
      following ACL reconstruction. Part I: development of a new test battery.

PMID- 25749657
TI  - Marine pollution and assessment of marine status in Latin America.

PMID- 25749656
TI  - Patterns of cancer care costs in a country with detailed individual data.
AB  - OBJECTIVE: To determine health system expenditure on cancers by time since
      diagnosis using data for an entire country. METHODS: New Zealand cancer registry
      data was linked to hospitalization, pharmaceutical, outpatient, general practice,
      laboratory, and other datasets, with costs ascribed to each event occurring in
      2006-2011. "Excess" cancer costs were estimated by subtracting "expected costs"
      for citizens without cancer from the "total cost" for cancer patients ($2011
      inflation-adjusted). Gamma regressions were used to estimate costs per person
      month. RESULTS: For first adult cancer diagnosed that the excess cost per person
      was between US$3400 and US$4300 in the first month postdiagnosis (varied by sex
      and age), fell to US$50-US$150 per month at 2 or more years postdiagnosis
      (excluding those within a year of death), but increased again if dying from their
      cancer (US$3800-US$8300 in the last month of life). Such patterns varied by
      cancer, for example, in the first month postdiagnosis for 65 year olds it varied
      20-fold from US$800 for prostate to US$15,900 for brain cancer. Per diagnosed
      case, total excess costs varied from US$5000 (melanoma) to US$66,000 (bone and
      connective tissue) [Corrected]. Excess cancer costs made up 6.5% of total
      Vote:Health expenditure in 2010-2011, with colorectal (14.7%), breast (14.4%)
      being the top 2 contributors, and prostate, non-Hodgkin lymphoma, leukemia, and
      lung each contributing about 6%. CONCLUSIONS: Costs vary substantially by time
      since diagnosis and cancer type. The results and regression equations reported in
      this paper can be used in modeling requiring cancer costs by time since diagnosis
      and proximity to death.

PMID- 25749658
TI  - Effects of complementary and integrative medicine on cancer survivorship.
AB  - Cancer survivorship has become a topic of great interest in the past few years.
      Unfortunately, even with successful treatment as well as good follow-up care,
      many patients continue to experience unmet physical, emotional, and spiritual
      needs as well as having an unsettling fear, fear of recurrence, a fear which most
      survivors share, even many years after their treatment ended. As a result,
      patients are continually looking for additional ways to address these needs and
      fears. Among the most popular approach is the use of complementary and
      integrative medicine (CIM). Most studies on CIM use among cancer patients and
      survivors concentrate on symptom improvement and improvement of quality of life
      and do not touch a crucial question if these therapies can affect patients'
      survival in terms of prolongation of life. Interestingly, in recent years, there
      are a growing number of studies that suggest that approaches such as mind-body
      interventions, enhanced general nutrition, nutritional supplements, physical
      activity, and other CIM approaches may have a positive effect on survival of
      cancer patients. Although additional studies are needed to confirm these
      findings, given the low cost of these CIM interventions, their minimal risk, and
      the potential magnitude of their effects, these approaches might be considered as
      additional important tools to integrate into cancer survivorship care plans. 

PMID- 25749659
TI  - Low-level red laser improves healing of second-degree burn when applied during
      proliferative phase.
AB  - The aim of this study was to investigate the effects of low-level red laser on
      tissue repair in rats submitted to second-degree burn, evaluating if the timing
      of laser treatment influences the healing process. The animals had their backs
      shaved and divided as follows: control group (n = 12)-rats burned and not
      irradiated, early laser group (n = 12)-rats burned and irradiated from day 1
      after injury for five consecutive days, and late laser group (n = 14)-rats burned
      and irradiated from day 4 after injury for five consecutive days. Laser
      irradiation was according to a clinical protocol (20 J/cm(2), 100 mW, continuous
      wave emission mode, 660 nm) as recommended by the laser device manufacturer. Half
      of the animals were sacrificed 10 days after burn, and the other animals were
      sacrificed 21 days after burn. The late laser group accelerated wound contraction
      10 and 21 days after burn. The late laser group accelerated reepithelialization
      18 days after burn. The late laser group increases the granulation tissue 10 and
      21 days after burn. Both irradiated groups increased type III collagen expression
      and TGF-beta 21 days after burn. Both irradiated groups increased macrophage and
      myofibroblast numbers 10 days after burn and decreased 21 days after. Low-level
      red laser exposure contributes to the process of tissue repair of second-degree
      burns, but the intervention during proliferative phase is crucial in the final
      outcome of the repair process. 

PMID- 25749660
TI  - Regulation of myelopoiesis by the transcription factor IRF8.
AB  - Interferon regulatory factor-8 (IRF8) is a transcription factor expressed in
      hematopoietic cells, particularly in mononuclear phagocytes
      [monocytes/macrophages and dendritic cells (DCs)] and their progenitors. Various
      studies have demonstrated that IRF8 is essential for the development of
      monocytes, DCs, eosinophils, and basophils. Conversely, IRF8 suppresses the
      generation of neutrophils. Accordingly, Irf8 (-/-) mice develop immunodeficiency
      and a chronic myeloid leukemia (CML)-like disease. Mutations and loss of
      expression of the human IRF8 gene are also associated with immunodeficiency and
      CML, respectively. Recent findings have begun to reveal the transcription factor
      network and epigenetic changes governed by IRF8. For example, in mononuclear
      phagocyte progenitors, IRF8 cooperates with PU.1 to promote the formation of
      promoter-distal enhancers to induce monocyte-related genes including the critical
      downstream transcription factor gene Klf4. On the other hand, IRF8 blocks
      C/EBPalpha activity to suppress the neutrophil differentiation program. Indeed,
      Irf8 (-/-) mononuclear phagocyte progenitors fail to efficiently generate
      monocytes and DCs and, instead, aberrantly give rise to neutrophils. This article
      provides an overview of recent advances in our understanding of the role of IRF8
      in myelopoiesis and related diseases. 

PMID- 25749661
TI  - Pseudo-Pelger-Huet anomaly and granulocytic dysplasia associated with human
      granulocytic anaplasmosis.
AB  - Pseudo-Pelger-Huet anomaly (PHA) refers to mono- or bi-lobed granulocytes,
      reportedly observed in patients with severe infections and inflammation or
      hematological malignancies including myelodysplastic syndrome (MDS) or acute
      myeloid leukemia (AML). Dysplastic changes in granulocytes are typical
      manifestations in MDS and granulocytic leukemias. Here, we report the unique case
      of a patient found to have human granulocytic anaplasmosis (HGA), a tick-borne
      disease caused by Anaplasma phagocytophilum, a Gram-negative coccobacillus. This
      patient showed striking hematological manifestations including a large number of
      pseudo-PHA, a severe degree of left shift, and dysplastic granulocytes. These
      hematological presentations on the peripheral smear all resolved with doxycycline
      treatment, implying that the changes were most likely reactive manifestations
      secondary to HGA, rather than underlying hematological malignancies such as MDS
      or AML. 

PMID- 25749662
TI  - Phase I study of pegylated liposomal doxorubicin in combination with bortezomib
      for Japanese patients with relapsed or refractory multiple myeloma.
AB  - This phase I open-label study evaluated the tolerability of pegylated liposomal
      doxorubicin (PLD) and bortezomib combination in Japanese patients with relapsed
      or refractory multiple myeloma. Eligible patients (>=20 years) who had >=1 line
      of prior chemotherapy received bortezomib 1.3 mg/m(2) rapid intravenous infusion
      on days 1, 4, 8 and 11 (each 21-day cycle), followed by PLD 30 mg/m(2)
      intravenous infusion on day 4 (each cycle), up to 6 cycles. Dose-limiting
      toxicity (DLT), defined as Grade 4 hematologic or Grade >=3 non-hematologic, was
      evaluated through end of day 21. All three patients enrolled in the study
      developed DLTs [Grade 4 thrombocytopenia (n = 2) and Grade 3 ileus (n = 1)]. The
      study was, therefore, terminated without adding new patients, as per protocol
      specified criteria. The most common Grade 3-4 adverse events (AEs) were
      hematologic, including thrombocytopenia, leucopenia, and neutropenia. The
      treatment was prematurely discontinued in all three patients due to AEs: Grade 3
      bronchiolitis (serious AE), Grade 3 peripheral sensory neuropathy, and Grade 2
      stomatitis. All patients achieved partial response (efficacy, secondary
      endpoint). In conclusion, the tolerability of PLD and bortezomib combination at
      dose levels approved in various countries was not confirmed in relapsed or
      refractory multiple myeloma patients from Japan.

PMID- 25749663
TI  - Targeted spontaneous reporting of suspected renal toxicity in patients undergoing
      highly active anti-retroviral therapy in two public health facilities in Uganda.
AB  - BACKGROUND: Although the national HIV control programme in Uganda has a well
      established system for monitoring disease progression and treatment outcomes,
      monitoring of adverse drug reactions (ADRs) is inadequate. In order to address
      under-reporting of ADRs, the National Pharmacovigilance Centre, in collaboration
      with the HIV control programme, piloted a targeted spontaneous reporting (TSR)
      system as a complementary method to traditional spontaneous reporting. METHODS:
      From April 2012 to March 2014, all cases of suspected renal toxicity in 10,225
      patients on tenofovir-based regimens were monitored in the regional
      pharmacovigilance centres of Masaka and Mbale. The identification of renal
      toxicity was performed using serum creatinine, urinalysis, and other signs and
      symptoms of kidney injury. RESULTS: There was one suspected renal toxicity
      reported for every 200 patients on a tenofovir-based regimen. Some of the serious
      reactions reported were death in two cases and bone demineralisation in five
      patients. Most of patients had been on treatment for 2 years. Those that had been
      on tenofovir for more than 4 years had raised serum creatinine levels,
      emphasising the importance of monitoring for the risk of renal damage for longer.
      We also found that the reporting rate of suspected ADRs for all medicines in the
      two sites increased almost fivefold during the implementation period. CONCLUSION:
      Although the occurrence of suspected tenofovir renal toxicity of HIV patients is
      low, there is need to monitor those at risk so as to prevent irreversible kidney
      injury. TSR can complement spontaneous reporting for collecting safety data on
      particular drugs and increase ADR reporting rates.

PMID- 25749664
TI  - The effect of pulmonary hypertension on aerobic exercise capacity in lung
      transplant candidates with advanced emphysema.
AB  - PURPOSE: Mild pulmonary hypertension (PH) in patients with advanced COPD is
      common, but its effects on exercise capacity are controversial. The objective of
      our study was to investigate the effects of mild PH (35 > mPAP >= 25 mmHg) on
      exercise capacity in patients with advanced emphysema, candidates for lung
      transplantation. METHODS: We retrospectively reviewed and compare the data from
      right heart catheterization and cardiopulmonary exercise test, performed in
      patients with advanced emphysema, candidate for lung transplantation. RESULTS:
      Twenty patients with emphysema and no PH and 24 patients with emphysema
      associated with mild PH included in the study. Both patient groups had severe
      airways obstruction with markedly reduced FEV1 (24.9% P +/- 8.9 and 25.9% P +/-
      11.7, respectively), and severely reduced DLCO (35.2% P +/- 17.3 and 39.2% P +/-
      15.9). Both patients group demonstrated mark reduction in maximum workload and
      peak VO2 together with increased ventilatory equivalent for CO2 and extremely low
      breathing reserve. There was no correlation between mPAP and any of the exercise
      measurement. CONCLUSIONS: Our study suggests that exercise capacity in patients
      with advanced emphysema is limited by the ventilatory impairment and the presence
      of mild PH has no farther impact on exercise capability.

PMID- 25749665
TI  - Transforming and simplifying the treatment of pulmonary embolism: "safe dose"
      thrombolysis plus new oral anticoagulants.
AB  - BACKGROUND: Administration of systemic thrombolysis in pulmonary embolism (PE)
      has been limited to severe forms due to the risk of intracerebral hemorrhage
      (ICH). There is growing evidence from small studies that low-dose systemic
      thrombolysis has equal efficacy to standard dose, while eliminating the risk of
      ICH. Little data exists on the combined use of low-dose systemic thrombolysis and
      new oral anticoagulants (NOAC). We evaluated the clinical and echocardiographic
      outcome of patients treated with low or "safe dose" thrombolysis (SDT) and NOAC
      at intermediate term. METHODS: We retrospectively identified 159 patients with
      massive and submassive PE who were treated with SDT and NOAC over a 2-year period
      by our group. They were followed prospectively for PE-related mortality,
      recurrent PE, bleeding, change in right/left ventricle (RV/LV) size, pulmonary
      artery systolic pressure (PASP), and clinical improvement at a mean follow-up of
      18 +/- 3 months. RESULTS: At 6 months, the RV/LV size was reduced from 1.29 +/-
      0.28 to 0.89 +/- 0.03 (p < 0.001). The PASP dropped from 53.12 +/- 3.85 mmHg to
      30.39 +/- 3.93 mmHg (p < 0.001). There was no ICH or in-hospital major or minor
      bleeding. At 18 months, three patients died of cancer. Recurrent PE developed in
      one patient who had been later switched to warfarin. The duration of
      hospitalization was 1.8 +/- 0.3 days. CONCLUSION: With combination of SDT and
      NOAC, treatment of massive and submassive PE becomes identical and is transformed
      from an "anticoagulation first" to a "thrombolysis first" approach, thereby
      making treatment streamlined, simple, safe and effective, accessible and
      inexpensive.

PMID- 25749667
TI  - Intrapulmonary mature teratoma mimicking a fungus ball.

PMID- 25749666
TI  - An experimental model-based exploration of cytokines in ablative radiation
      induced lung injury in vivo and in vitro.
AB  - INTRODUCTION: Stereotactic ablative radiotherapy is a newly emerging radiotherapy
      treatment method that, compared with conventionally fractionated radiation
      therapy (CFRT), allows an ablative dose of radiation to be delivered to a
      confined area around a tumor. The aim of the present study was to investigate the
      changes of various cytokines that may be involved in ablative radiation-induced
      lung injury in vitro and in vivo. METHODS: In the in vivo study, ablative-dose
      radiation was delivered to a small volume of the left lung of C3H/HeJCr mice
      using a small-animal irradiator. The levels of 24 cytokines in the peripheral
      blood were tested at several time points after irradiation. For the in vitro
      study, three mouse cell types (type II pneumocytes, alveolar macrophages, and
      fibroblasts) known to play important roles in radiation-induced pneumonitis and
      lung fibrosis were analyzed using a co-culture system. RESULTS: In the in vivo
      study, we found obvious patterns of serum cytokine changes depending on the
      volume of tissue irradiated (2-mm vs. 3.5-mm collimator). Only the levels of 3
      cytokines increased with the 2-mm collimator at the acute phase (1-2 weeks after
      irradiation), while the majority of cytokines were elevated with the 3.5-mm
      collimator. In the in vitro co-culture system, after the cells were given an
      ablative dose of irradiation, the levels of five cytokines (GM-CSF, G-CSF, IL-6,
      MCP-1, and KC) increased significantly in a dose-dependent manner. CONCLUSIONS:
      The cytokine levels in our radiation-induced lung injury model showed specific
      changes, both in vivo and in vitro. These results imply that biological studies
      related to ablative-dose small-volume irradiation should be investigated using
      the corresponding experimental models rather than on those simulating large
      volume CFRT.

PMID- 25749668
TI  - Drugs prescribed by medical students: a suitable practice?

PMID- 25749669
TI  - Has New York City fallen into the local trap?
AB  - OBJECTIVES: Municipal policies aiming to improve equity in food access and health
      often rely on the assumption that neighborhoods with limited healthy food
      availability and high levels of diet-related illness should be the subject of
      targeted policy-driven change. This study explored this assumption in the context
      of recent food policy developments in New York City with the objective of
      empirically examining the geography of everyday food behavior in high- and low
      income neighborhoods. STUDY DESIGN: This research used a multi method comparative
      design. Areas at the poles of income inequality in New York City were identified
      using census data and geographic information systems. Qualitative and geographic
      data were collected from individual eaters living and/or working in those areas.
      METHODS: A review of food policies in New York City from 2005 to 2012.
      Qualitative and geographic data were collected using space-time food diaries and
      mental mapping interviews. RESULTS: People living in the low-income study area
      had more localized food geographies than residents of the high-income study area.
      Individual-level qualitative data revealed that eaters with the least financial
      resources, those with physical disabilities, and those who were unemployed
      reported all or nearly all of their food events taking place within their
      neighborhoods. Eaters from the low-income area suggested that the barriers to
      healthy food that policy incentives should address were the high price of food
      and the consumer environment within stores, not the number of supermarkets in
      their area. Residents of the high-income area also expressed dissatisfaction with
      food prices and the in-store environment of their local supermarkets. These
      eaters leveraged their financial, technological, and transportation resources to
      overcome those barriers to fresh food. CONCLUSIONS: The policy review found that
      New York City's recent nutrition and food policies are to a great extent
      geographically targeted to low-income areas. As such, they miss opportunities for
      citywide interventions that would create food environment changes welcomed by
      residents of both high- and low-income areas. The recent nutrition and food
      policies also have the potential unintended negative consequence of promoting
      gentrification.

PMID- 25749670
TI  - Work-site wellness programmes in Sweden: a cross-sectional study of physical
      activity, self-efficacy, and health.
AB  - In Sweden, a work-site wellness programme implies reimbursing some of the
      expenses for health-promoting activities. Although work-site wellness programmes
      are readily available in Sweden, a large number of employees elect not to
      participate. OBJECTIVES: The aim of this study was to investigate the association
      of physical activity, self-reported general health assessment and self-efficacy
      with participation in a work-site wellness programme. STUDY DESIGN: A cross
      sectional study design was used. METHODS: An online questionnaire was distributed
      to employees of a manufacturing company with 2500 employees in southwest Sweden.
      RESULTS: Those who took advantage of the work-site wellness programme assessed
      their general health as better and had higher assessment of physical activity.
      The study showed that being enlisted also implies a higher level of physical
      activity and general health; however, the effect sizes of these correlations were
      small. Self-efficacy, i.e. perceived behavioural control, was not associated with
      participation in the work-site wellness programme. However, self-efficacy was
      correlated with both general health assessment and physical activity. A
      regression analysis to determine explanatory contributions to the general health
      assessment score showed no significant contribution from participation in a work
      site wellness programme, but was instead explained by perceived behavioural
      control and physical activity. CONCLUSIONS: Given the small effect size of the
      difference in physical activity between participators and non-participators in
      the work-site wellness programme, it is probable that only a small proportion of
      participators changed their health-promoting activities as a result of the work
      site wellness programme.

PMID- 25749671
TI  - Population-based incidence and cost of non-fatal injuries in Iran: a consistent
      under-recognized public health concern.
AB  - OBJECTIVES: To investigate the incidence and determinants of non-fatal injuries,
      and the cost imposed on victims in an Iranian population aged 15-64 years.
      DESIGN: Cross-sectional household survey. METHODS: Three-stage probability
      sampling was conducted for selection of a representative sample of Iranians. Data
      on the demographics, history and cost of injury were obtained from face-to-face
      interviews and telephone calls. RESULTS: In total, 7886 subjects were included in
      this study. The annual incidence rate of all injuries was 905 (95% confidence
      interval 853-957) per 1000 population (approximately nine injuries per ten
      Iranians). The mean (+/-standard error) incidence rates of first aid injuries
      (FAIs; medical care not required) and medical-attended injuries (MAIs; medical
      treatment sought) were 737 +/- 24 and 168 +/- 12 per 1000 population,
      respectively. Young, urban females were at highest risk for FAIs, and single
      males were at highest risk for MAIs. The most common injury description was as
      follows: non-paid work (activity), home (place), inanimate mechanical force
      (mechanism), upper limb (site of injury) and open wound (type of injury). For
      MAIs, the most common place of treatment was hospital. Traffic-related injuries
      had the highest total cost and the lowest out-of-pocket cost. Total and out-of
      pocket costs of non-fatal injuries in Iran in 2011 have been estimated to be
      US$6,111,138,000 and US$1,480,411,000, respectively. CONCLUSION: Non-fatal
      injuries are an under-recognized public health problem. Cost-control policies are
      essential to reduce the out-of-pocket cost of injuries.

PMID- 25749672
TI  - Global health education in the United Kingdom: a review of university
      undergraduate and postgraduate programmes and courses.
AB  - OBJECTIVES: This study reviews the current state of global health education (GHE)
      in the United Kingdom (UK) through the collation and synthesis of data on
      undergraduate and postgraduate global health degree programmes. It examines both
      the curriculum provided and profile of the student currently studying global
      health in the UK. STUDY DESIGN: Descriptive, case study design. METHODS: A
      systematic review of the literature identified a set of global health 'core
      competencies' that students could acquire through their chosen programme of
      study. Those competencies were synthesized and then compared to core and elective
      courses currently offered by global health degree programmes at UK universities.
      A questionnaire was designed and sent electronically to all global health
      Programme Directors requesting generic information regarding the profile of their
      global health students. RESULTS: Fifteen universities in the UK, based in England
      and Scotland, offered twenty-five postgraduate and six undergraduate global
      health degree programmes in 2012-13. Two Universities were developing a full,
      three-year, undergraduate degree programme in global health. Sixteen core
      competencies for a medical and non-medical student constituency were identified.
      Of these, just three 'core competencies' - epidemiology of tropical diseases,
      health systems (including health system management), and health care services -
      corresponded directly to core and elective courses offered by >50% of UK
      universities. The five most frequently offered subjects were: health systems
      (including health system management), research methods, public health (including
      specialisations in prevention, treatment and care), epidemiology, and health
      economics. CONCLUSIONS: GHE in UK universities has seen comparable growth to
      North American institutions, becoming Europe's regional hub for undergraduate and
      postgraduate courses and programmes. As with the US and Canadian experience, GHE
      at the undergraduate level is offered primarily to medical students through
      intercalated degree programmes. At the postgraduate level, there is more
      innovation in content and mode of delivery, with a small number of UK
      universities providing students from a diversity of backgrounds the opportunity
      to study global health from multidisciplinary perspectives. Distance learning is
      also seeking to make the delivery of GHE truly global, with a growing number of
      universities recognizing its potential to further innovate in global health
      pedagogy. While demand for GHE is predicted to remain robust, to ensure the needs
      of students and practitioners are met, more critical reflection on global health
      curricula, the desired profile of graduates, and equity of access is required.

PMID- 25749673
TI  - Effectiveness of high-intensity nutritional interventions for overweight
      Brazilian women.

PMID- 25749674
TI  - Parental smoking and exposure to environmental tobacco smoke are associated with
      waterpipe smoking among youth: results from a national survey in Lebanon.
AB  - OBJECTIVES: Waterpipe tobacco smoking (WTS) is a growing public health concern
      worldwide yet little is known about the epidemiology of use among young people.
      The objectives of this study were to examine the prevalence, patterns and
      correlates of WTS among students across Lebanon. STUDY DESIGN: The study design
      was a cross sectional survey. METHODS: 126-item tobacco questionnaire was
      conducted among 1128 sixth and seventh grade students across Lebanon. Current
      patterns of use were descriptively analysed, and logistic regression models
      examined correlates of WTS. RESULTS: Ever WTS prevalence was 44.3%, current WTS
      prevalence was triple that of cigarettes (22.1% vs 7.4%), and 40.0% of current
      users were at least weekly or daily smokers. Initiation and patterns of use, as
      well as addiction and cessation attitudes have been reported. Significant
      correlates of current WTS included older age, reduced religiosity, peer and
      parent tobacco use, recent waterpipe advertisement exposure, increased
      pluralistic ignorance and current cigarette use. Significant correlates of ever
      WTS were similar to current WTS, but included second hand waterpipe tobacco smoke
      exposure at home and did not include recent waterpipe advertisement exposure.
      Neither gender nor socio-economic status were significant correlates of current
      or ever WTS. CONCLUSIONS: Waterpipe is the most common form of tobacco smoking,
      and is used regularly, among sixth and seventh grade Lebanese students. It should
      be considered a public health priority with increased tobacco surveillance and
      legislation. Widespread educational and policy interventions might help
      denormalize the social acceptability of WTS. Meanwhile, more research is needed
      to understand the changing paradigm of WTS epidemiology and the health outcomes
      among young smokers.

PMID- 25749675
TI  - The efficiency of second order orientation coherence detection.
AB  - Neurons in early visual cortex respond to both luminance- (1st order) and
      contrast-modulated (2nd order) local features in the visual field. In later extra
      striate areas neurons with larger receptive fields integrate information across
      the visual field. For example, local luminance-defined features can be integrated
      into contours and shapes. Evidence for the global integration of features defined
      by contrast-modulation is less well established. While good performance in some
      shape tasks has been demonstrated with 2nd order stimuli, the integration of
      contours fails with 2nd order elements. Recently we developed a global
      orientation coherence task that is more basic than contour integration, bearing
      similarity to the well-established global motion coherence task. Similar to our
      previous 1st order result for this task, we find 2nd order coherence detection to
      be scale-invariant. There was a small but significant threshold elevation for 2nd
      order relative to 1st order. We used a noise masking approach to compare the
      efficiency of orientation integration for the 1st and 2nd order. We find a
      significant deficit for 2nd order detection at both the local and global level,
      however the small size of this effect stands in stark contrast against previous
      results from contour-integration experiments, which are almost impossible with
      2nd order stimuli. 

PMID- 25749676
TI  - Allocentric coding: spatial range and combination rules.
AB  - When a visual target is presented with neighboring landmarks, its location can be
      determined both relative to the self (egocentric coding) and relative to these
      landmarks (allocentric coding). In the present study, we investigated (1) how
      allocentric coding depends on the distance between the targets and their
      surrounding landmarks (i.e. the spatial range) and (2) how allocentric and
      egocentric coding interact with each other across targets-landmarks distances
      (i.e. the combination rules). Subjects performed a memory-based pointing task
      toward previously gazed targets briefly superimposed (200ms) on background images
      of cluttered city landscapes. A variable portion of the images was occluded in
      order to control the distance between the targets and the closest potential
      landmarks within those images. The pointing responses were performed after large
      saccades and the reappearance of the images at their initial location. However,
      in some trials, the images' elements were slightly shifted (+/-3 degrees ) in
      order to introduce a subliminal conflict between the allocentric and egocentric
      reference frames. The influence of allocentric coding in the pointing responses
      was found to decrease with increasing target-landmarks distances, although it
      remained significant even at the largest distances (?10 degrees ). Interestingly,
      both the decreasing influence of allocentric coding and the concomitant increase
      in pointing responses variability were well captured by a Bayesian model in which
      the weighted combination of allocentric and egocentric cues is governed by a
      coupling prior. 

PMID- 25749677
TI  - The 'laws' of binocular rivalry: 50 years of Levelt's propositions.
AB  - It has been fifty years since Levelt's monograph On Binocular Rivalry (1965) was
      published, but its four propositions that describe the relation between stimulus
      strength and the phenomenology of binocular rivalry remain a benchmark for
      theorists and experimentalists even today. In this review, we will revisit the
      original conception of the four propositions and the scientific landscape in
      which this happened. We will also provide a brief update concerning distributions
      of dominance durations, another aspect of Levelt's monograph that has maintained
      a prominent presence in the field. In a critical evaluation of Levelt's
      propositions against current knowledge of binocular rivalry we will then
      demonstrate that the original propositions are not completely compatible with
      what is known today, but that they can, in a straightforward way, be modified to
      encapsulate the progress that has been made over the past fifty years. The
      resulting modified, propositions are shown to apply to a broad range of bistable
      perceptual phenomena, not just binocular rivalry, and they allow important
      inferences about the underlying neural systems. We argue that these inferences
      reflect canonical neural properties that play a role in visual perception in
      general, and we discuss ways in which future research can build on the work
      reviewed here to attain a better understanding of these properties. 

PMID- 25749678
TI  - Synthesis, antifungal activity and QSAR of some novel carboxylic acid amides.
AB  - A series of novel aromatic carboxylic acid amides were synthesized and tested for
      their activities against six phytopathogenic fungi by an in vitro mycelia growth
      inhibition assay. Most of them displayed moderate to good activity. Among them N
      (2-(1H-indazol-1-yl)phenyl)-2-(trifluoromethyl)benzamide (3c) exhibited the
      highest antifungal activity against Pythium aphanidermatum (EC50 = 16.75 ug/mL)
      and Rhizoctonia solani (EC50 = 19.19 ug/mL), compared to the reference compound
      boscalid with EC50 values of 10.68 and 14.47 ug/mL, respectively. Comparative
      molecular field analysis (CoMFA) and comparative molecular similarity indices
      analysis (CoMSIA) were employed to develop a three-dimensional quantitative
      structure-activity relationship model for the activity of the compounds. In the
      molecular docking, a fluorine atom and the carbonyl oxygen atom of 3c formed
      hydrogen bonds toward the hydroxyl hydrogens of TYR58 and TRP173. 

PMID- 25749679
TI  - Untargeted NMR-based methodology in the study of fruit metabolites.
AB  - In this review, fundamental aspects of the untargeted NMR-based methodology
      applied to fruit characterization are described. The strategy to perform the
      structure elucidation of fruit metabolites is discussed with some examples of
      spectral assignments by 2D experiments. Primary ubiquitous metabolites as well as
      secondary species-specific metabolites, identified in different fruits using an
      untargeted 1H-NMR approach, are summarized in a comprehensive way. Crucial
      aspects regarding the quantitative elaboration of spectral data are also
      discussed. The usefulness of the NMR-based metabolic profiling was highlighted
      using some results regarding quality, adulteration, varieties and geographical
      origin of fruits and fruit-derived products such as juices. 

PMID- 25749680
TI  - Nitric oxide released from luminal s-nitroso-N-acetylcysteine increases gastric
      mucosal blood flow.
AB  - Nitric oxide (NO)-mediated vasodilation plays a key role in gastric mucosal
      defense, and NO-donor drugs may protect against diseases associated with gastric
      mucosal blood flow (GMBF) deficiencies. In this study, we used the ex vivo
      gastric chamber method and Laser Doppler Flowmetry to characterize the effects of
      luminal aqueous NO-donor drug S-nitroso-N-acetylcysteine (SNAC) solution
      administration compared to aqueous NaNO2 and NaNO3 solutions (pH 7.4) on GMBF in
      Sprague-Dawley rats. SNAC solutions (600 MUM and 12 mM) led to a rapid threefold
      increase in GMBF, which was maintained during the incubation of the solutions
      with the gastric mucosa, while NaNO2 or NaNO3 solutions (12 mM) did not affect
      GMBF. SNAC solutions (600 MUM and 12 mM) spontaneously released NO at 37  degrees
      C at a constant rate of 0.3 or 14 nmol.mL-1.min-1, respectively, while NaNO2 (12
      mM) released NO at a rate of 0.06 nmol.mL-1.min-1 and NaNO3 (12 mM) did not
      release NO. These results suggest that the SNAC-induced GMBF increase is due to
      their higher rates of spontaneous NO release compared to equimolar NaNO2
      solutions. Taken together, our data indicate that oral SNAC administration is a
      potential approach for gastric acid-peptic disorder prevention and treatment. 

PMID- 25749681
TI  - Carbopol-incorporated thermoreversible gel for intranasal drug delivery.
AB  - The present study describes the preparation and evaluation of a poloxamer 407
      (P407)-based thermoreversible gel using Carbopol 934P (C934P) as a mucoadhesive
      polymer and hydroxypropyl-beta-cyclodextrin (HP-beta-CD) for enhancing the
      aqueous solubility and intranasal absorption of fexofenadine hydrochloride (FXD
      HCl). The prepared gels were characterized by gelation temperature,
      viscoelasticity, and drug release profile. Thermoreversibility of P407/C934P gel
      was demonstrated by rheological studies. The incorporation of carbopol into P407
      gel also reduced the amounts of drug released from the gel formulations (p <
      0.05). In vivo pharmacokinetic results of the prepared gel formulations in
      rabbits (at 0.5 mg/kg dose) showed that the relative bioavailability of drug from
      P407/C934P gel was 11.3 and 2.7-fold higher than those of drug solution and P407
      gel group, respectively. These findings suggested that developed thermoreversible
      gels could be used as promising dosage forms to improve intranasal drug
      absorption. 

PMID- 25749682
TI  - DNA-catalyzed Henry reaction in pure water and the striking influence of organic
      buffer systems.
AB  - In this manuscript we report a critical evaluation of the ability of natural DNA
      to mediate the nitroaldol (Henry) reaction at physiological temperature in pure
      water. Under these conditions, no background reaction took place (i.e., control
      experiment without DNA). Both heteroaromatic aldehydes (e.g., 2
      pyridinecarboxaldehyde) and aromatic aldehydes bearing strong or moderate
      electron-withdrawing groups reacted satisfactorily with nitromethane obeying
      first order kinetics and affording the corresponding beta-nitroalcohols in good
      yields within 24 h. In contrast, aliphatic aldehydes and aromatic aldehydes
      having electron-donating groups either did not react or were poorly converted.
      Moreover, we discovered that a number of metal-free organic buffers efficiently
      promote the Henry reaction when they were used as reaction media without adding
      external catalysts. This constitutes an important observation because the
      influence of organic buffers in chemical processes has been traditionally
      underestimated. 

PMID- 25749683
TI  - Tethering in RNA: an RNA-binding fragment discovery tool.
AB  - Tethering has been extensively used to study small molecule interactions with
      proteins through reversible disulfide bond forming reactions to cysteine
      residues. We describe the adaptation of Tethering to the study of small molecule
      binding to RNA using a thiol-containing adenosine analog (ASH). Among 30
      disulfide-containing small molecules screened for efficient Tethering to ASH
      bearing RNAs derived from pre-miR21, a benzotriazole-containing compound showed
      prominent adduct formation and selectivity for one of the RNAs tested. The
      results of this screen demonstrate the viability of using thiol-modified nucleic
      acids to discover molecules with binding affinity and specificity for the purpose
      of therapeutic compound lead discovery. 

PMID- 25749684
TI  - Answer to the Letter to the Editor of C. Brembilla et al. concerning "Dynamic
      cervical myelopathy in young adults" by Hattou L, Morandi X, Le Reste PJ, et al:
      Eur Spine J 2014, 23:1515-22.

PMID- 25749686
TI  - Poena, the goddess of divine retribution.

PMID- 25749685
TI  - Letter to the Editor concerning "Anterior stand-alone fusion revisited: a
      prospective clinical, X-ray and CT investigation" by C. J. Siepe, K. Stosch
      Wiechert, F. Heider, et al. Eur Spine J; 2014 Dec 5. DOI 10.1007/s00586-014-3642
      y: [Epub ahead of print]: Can the Radiological Evaluation on the Sagittal
      Alignment be ignored at the Final Follow-up?

PMID- 25749687
TI  - Anterior transoral atlantoaxial release and posterior instrumented fusion for
      irreducible congenital basilar invagination.
AB  - PURPOSE: Recently, it has been demonstrated that anterior release of tight
      structures via a transoral approach can assist posterior distraction-reduction
      technique in restoring the cranio-cervical anatomy in irreducible atlantoaxial
      dislocations. Our aim was to evaluate the radiological and clinical outcome of
      anterior release and posterior instrumentation for irreducible congenital basilar
      invagination. METHODS: A consecutive series of 15 patients (2007-2009) with
      irreducible congenital basilar invagination were treated with anterior release
      using transoral approach. A retrospective chart review was performed. All
      patients presented with myelopathy. Dislocation was treated as irreducible if
      acceptable reduction was not achieved with traction under general anesthesia and
      neuromuscular paralysis. The anterior release comprised of transverse sectioning
      the longus colli and capitis, C1-C2 joint capsular release and intra-articular
      adhesiolysis with or without anterior C1 arch excision. Cantilever mechanism
      using posterior instrumentation was used to correct any residual malalignment.
      RESULTS: Mean age was 21.4 (10-50) years. Average duration of follow-up was 28
      (24-40) months. The average preoperative JOA score was 11.4 (8-16), which
      improved to 15.4 (10-18) after surgery. Anatomical reduction was achieved in
      thirteen patients. Fusion was documented in all patients. Complications included
      persistent nasal phonation in one, and superficial wound dehiscence in one.
      CONCLUSION: We believe that a significant number of irreducible dislocations can
      be anatomically reduced with this procedure thus avoiding odontoid excision.
      Encouraging results from this short series have given us a new perspective in
      dealing with these challenging problems.

PMID- 25749688
TI  - A MRI study of lumbar plexus with respect to the lateral transpsoas approach to
      the lumbar spine.
AB  - PURPOSE: To evaluate the relative position between lumbar plexus and access
      corridor of minimally invasive lateral transpsoas lumbar approach, as well as the
      approach safety. METHODS: Three-dimensional fast imaging employing steady-state
      acquisition (3D FIESTA) sequence images of lumbar spine were obtained from 58
      patients with lumbar degenerative diseases for reconstruction to analyze the
      distribution of lumbar plexus from L1-L2 to L4-L5 level with respect to the
      transpsoas lumbar approach. The axial image distance (AID) between the anterior
      edge of lumbar plexus and the sagittal central perpendicular line (SCPL) of disc
      was measured. SCPL was drawn perpendicularly to the sagittal plane of
      intervertebral disc and it passed through its central point, which is initial
      dilator trajectory for transpsoas approach. As related to the SCPL of disc, the
      distance with a positive value was set to indicate neural tissue posterior to it,
      while anterior to it was represented by a negative value. RESULTS: In relation to
      SCPL of disc, the AID of lumbar plexus was measured 13.01 +/- 1.70, 8.61 +/-
      2.26, 1.12 +/- 2.37 and -5.42 +/- 3.26 mm from L1-L2 to L4-L5 level,
      respectively, while the AID of genitofemoral nerve was recorded -1.13 +/- 2.87, 
      5.78 +/- 2.33 and -10.53 +/- 3.30 mm from L2-L3 to L4-L5 level accordingly.
      CONCLUSION: With respect to the SCPL of disc, a trajectory of guide wire or a
      radiographic reference landmark to place working channel, lumbar plexus lies
      posteriorly to it from L1-L2 to L3-L4 level and shifts anteriorly to it at L4-L5
      level, while genitofemoral nerve locates anteriorly to the SCPL from L2-L3 to L4
      L5 level. Neural retraction may take place during sequential dilation of access
      corridor especially at L4-L5 level.

PMID- 25749689
TI  - ALIF and total disc replacement versus 2-level circumferential fusion with TLIF:
      a prospective, randomized, clinical and radiological trial.
AB  - STUDY DESIGN: Prospective, randomized trial. PURPOSE: The treatment of
      degenerative disc disease (DDD) with two-level fusion has been associated with a
      reasonable rate of complications. The aim of the present study was to compare
      (Hybrid) stand-alone anterior lumbar interbody fusion (ALIF) at L5/S1 with total
      disc replacement at L4/5 (TDR) as an alternative surgical strategy to (Fusion) 2
      level circumferential fusion employing transforaminal lumbar interbody fusion
      (TLIF) with transpedicular stabilization at L4-S1. METHODS: A total of 62
      patients with symptomatic DDD of segments L5/S1 (Modic >=2 degrees ) and L4/5
      (Modic <=2 degrees ; positive discography) were enrolled; 31 were treated with
      Hybrid and 31 with Fusion. Preoperatively, at 0, 12, and a mean follow-up of 37
      months, clinical (ODI, VAS) and radiological evaluations (plain/extension-flexion
      radiographs evaluated for implant failure, fusion, global and segmental lordosis,
      and ROM) were performed. RESULTS: In 26 of 31 Hybrid and 24 of 31 Fusion patients
      available at the final follow-up, we found a significant clinical improvement
      compared to preoperatively. Hybrid patients had significantly lower VAS scores
      immediately postoperatively and at follow-up compared to Fusion patients. The
      complication rates were low and similar between the groups. Lumbar lordosis
      increased in both groups. The increase was mainly located at L4-S1 in the Hybrid
      group and at L1-L4 in the Fusion group. Hybrid patients presented with increased
      ROM at L4/5 and L3/4, and Fusion patients presented with increased ROM at L3/4,
      with significantly greater ROM at L3/4 compared to Hybrid patients at follow-up.
      CONCLUSIONS: Hybrid surgery is a viable surgical alternative for the presented
      indication. Approach-related inferior trauma and the balanced restoration of
      lumbar lordosis resulted in superior clinical outcomes compared to two-level
      circumferential fusion with TLIF.

PMID- 25749690
TI  - Methods to determine pedicle screw placement accuracy in spine surgery: a
      systematic review.
AB  - STUDY DESIGN: Systematic review. OBJECTIVES: The aims of this systematic review
      were: (1) to determine the most commonly used methods for assessing pedicle screw
      placement accuracy, and (2) assess the difference in pedicle screw placement
      accuracy between navigation and free-hand techniques according to the
      classification method. BACKGROUND DATA: Pedicle screw fixation and spine surgery
      have almost become synonymous. However, there is currently no gold standard
      method to assess pedicle screw placement accuracy. We reviewed the literature to
      determine current techniques used by spine surgeons for the assessment of pedicle
      screw accuracy. METHODS: We systematically reviewed the medical literature (OVID
      Medline, Embase, PubMed) to identify all articles published between 2010 and 2013
      that have assessed pedicle screw placement accuracy in humans. Two independent
      reviewers with a third independent mediator performed study screening, selection
      and data extraction using a blinded and objective protocol. RESULTS: A total of
      68 relevant articles were included in this systematic review, for a total of 3442
      patients, 60 cadavers and 43,305 pedicle screws. The most widely used method (37
      articles) was based on 2 mm breach increments measured on computer tomography
      images. The second most widely used method consisted of an "in" or "out"
      classification system (16 articles). The remaining 15 articles used variable
      classification systems. Our result suggests that an average of 91.4% of pedicle
      screws placed with free-hand or fluoroscopy technique where within the safe zone
      (<2 mm breach) in comparison to an average of 97.3% of pedicle screws using
      navigation (p < 0.001) for the 2 mm increment method. Similarly, the in or out
      classification also showed statistically significant difference between free-hand
      and navigated techniques (p < 0.001). CONCLUSION: The grading system based on 2
      mm increments seems to be the most widely accepted method for determining pedicle
      screw placement accuracy. All grading systems were based on imaging alone without
      taking into account the direction of the breach or patient's symptoms.

PMID- 25749691
TI  - Blogging as a viable research methodology for young people with arthritis: a
      qualitative study.
AB  - BACKGROUND: The development of services that are responsive to the needs of users
      is a health policy priority. Finding ways of engaging young people in research to
      gain insights into their particular experiences, perspectives, and needs is vital
      but challenging. These data are critical to improving services in ways that meet
      the needs of young people. OBJECTIVE: Our aim was to evaluate Web-based blogging
      as a viable method for understanding the daily experiences and condition
      management strategies of young people with juvenile arthritis. METHODS: To meet
      the objectives of the study, a qualitative approach was required to gather
      information on the experiences and perspectives of young people regarding the
      management of their condition and its daily impact. In collaboration with a group
      of young people with arthritis, a custom website was developed. This website
      provided the opportunity for young people (aged 11-19) with arthritis from a
      United Kingdom pediatric hospital to contribute blogs. It was designed so that
      young people were free to write about whatever was important to them, but the
      site also included some structure and prompts to facilitate the writing of blogs.
      Qualitative analytical procedures were employed, supported by NVivo software.
      RESULTS: Engagement in the study by young people was variable in terms of their
      participation rates, frequency of website visits, and the length of their blogs.
      Young people used the site in different ways, some responding to the website
      categories and prompts that the team created, while others used it as a diary to
      record their experiences and thoughts. In line with principles of qualitative
      inquiry, the data collection was participant-led. Young people were in control of
      what, how much, and how often they wrote. However, some young people expressed
      difficulty regarding knowing what they should blog about. For a number of
      reasons, discussed here, the blogs may also not be fully reflective of
      experiences and perspectives of the participants. However, the data obtained
      provided insights into young people's experiences of living with arthritis and
      their use of medicines in the context of their daily lives. CONCLUSIONS: Web
      based research with young people presents opportunities and challenges for
      researchers. Web-based blogging methodology has the potential to give young
      people and parents the space and empowerment to express their own ideas and
      concerns. However, this project suggests that it might not be the best way to
      engage a large diverse group of young people and might most effectively be
      combined with other approaches. Despite these limitations, the study provided
      valuable data about the experience and impact of living with a long-term
      condition from the perspectives of young people with arthritis.

PMID- 25749692
TI  - MRI and retinal abnormalities in isolated optic neuritis with myelin
      oligodendrocyte glycoprotein and aquaporin-4 antibodies: a comparative study.

PMID- 25749693
TI  - Effect of orthostatic hypotension on sustained attention in patients with
      autonomic failure.
AB  - INTRODUCTION: Orthostatic hypotension has been associated with impaired cognitive
      function, but cognitive function during orthostatic hypotension has hardly been
      studied. We studied the effect of orthostatic hypotension, induced by head-up
      tilt (HUT), on sustained attention in patients with autonomic failure. METHODS:
      We studied the sustained attention to response task (SART) in the supine position
      and during HUT in 10 patients with autonomic failure and 10 age-matched and sex
      matched controls. To avoid syncope, the tilting angle was tailored to patients to
      reach a stable systolic blood pressure below 100 mm Hg. Controls were all tilted
      at an angle of 60 degrees . Cerebral blood flow velocity, blood pressure and
      heart rate were measured continuously. RESULTS: In patients, systolic blood
      pressure was 61.4 mm Hg lower during HUT than in the supine position (p<0.001).
      Patients did not make more SART errors during HUT than in the supine position (
      1.3 errors, p=0.3). Controls made 2.3 fewer errors during SART in the HUT
      position compared to the supine position (p=0.020). SART performance led to an
      increase in systolic blood pressure (+11.8 mm Hg, p=0.018) and diastolic blood
      pressure (+5.8 mm Hg, p=0.017) during SART in the HUT position, as well as to a
      trend towards increased cerebral blood flow velocity (+3.8 m/s, p=0.101).
      DISCUSSION: Orthostatic hypotension in patients with autonomic failure was not
      associated with impaired sustained attention. This might partly be explained by
      the observation that SART performance led to a blood pressure increase. Moreover,
      the upright position was associated with better performance in controls and, to a
      lesser extent, also in patients.

PMID- 25749695
TI  - Antibiotics for treating acute chest syndrome in people with sickle cell disease.
AB  - BACKGROUND: The clinical presentation of acute chest syndrome is similar whether
      due to infectious or non-infectious causes, thus antibiotics are usually
      prescribed to treat all episodes. Many different pathogens, including bacteria,
      have been implicated as causative agents of acute chest syndrome. There is no
      standardized approach to antibiotic therapy and treatment is likely to vary from
      country to country. Thus, there is a need to identify the efficacy and safety of
      different antibiotic treatment approaches for people with sickle cell disease
      suffering from acute chest syndrome. This is an update of a Cochrane review first
      published in 2007, and previously updated in 2013. OBJECTIVES: To determine
      whether an empirical antibiotic treatment approach (used alone or in
      combination):1. is effective for acute chest syndrome compared to placebo or
      standard treatment;2. is safe for acute chest syndrome compared to placebo or
      standard treatment;Further objectives are to determine whether there are
      important variations in efficacy and safety:3. for different treatment
      regimens,4. by participant age, or geographical location of the clinical trials.
      SEARCH METHODS: We searched The Group's Haemoglobinopathies Trials Register,
      which comprises references identified from comprehensive electronic database
      searches and handsearching of relevant journals and abstract books of conference
      proceedings. We also searched the LILACS database (1982 to 23 February 2015),
      African Index Medicus (1982 to 23 February 2015). and the World Health
      Organization International Clinical Trials Registry Platform Search Portal (23
      February 2015).Date of most recent search of the Haemoglobinopathies Trials
      Register: 20 January 2015. SELECTION CRITERIA: We searched for published or
      unpublished randomised controlled trials. DATA COLLECTION AND ANALYSIS: Each
      author intended to independently extract data and assess trial quality by
      standard Cochrane Collaboration methodologies, but no eligible randomised
      controlled trials were identified. MAIN RESULTS: For this update, we were unable
      to find any randomised controlled trials on antibiotic treatment approaches for
      acute chest syndrome in people with sickle cell disease. AUTHORS' CONCLUSIONS:
      This update was unable to identify randomised controlled trials on efficacy and
      safety of the antibiotic treatment approaches for people with sickle cell disease
      suffering from acute chest syndrome. Randomised controlled trials are needed to
      establish the optimum antibiotic treatment for this condition.

PMID- 25749694
TI  - Regulation of the rplY gene encoding 5S rRNA binding protein L25 in Escherichia
      coli and related bacteria.
AB  - Ribosomal protein (r-protein) L25 is one of the three r-proteins (L25, L5, L18)
      that interact with 5S rRNA in eubacteria. Specific binding of L25 with a certain
      domain of 5S r-RNA, a so-called loop E, has been studied in detail, but
      information about regulation of L25 synthesis has remained totally lacking. In
      contrast to the rplE (L5) and rplR (L18) genes that belong to the polycistronic
      spc-operon and are regulated at the translation level by r-protein S8, the rplY
      (L25) gene forms an independent transcription unit. The main goal of this work
      was to study the regulation of the rplY expression in vivo. We show that the rplY
      promoter is down-regulated by ppGpp and its cofactor DksA in response to amino
      acid starvation. At the level of translation, the rplY expression is subjected to
      the negative feedback control. The 5'-untranslated region of the rplY mRNA
      comprises specific sequence/structure features, including an atypical SD-like
      sequence, which are highly conserved in a subset of gamma-proteobacterial
      families. Despite the lack of a canonical SD element, the rplY'-'lacZ single-copy
      reporter showed unusually high translation efficiency. Expression of the rplY
      gene in trans decreased the translation yield, indicating the mechanism of
      autogenous repression. Site-directed mutagenesis of the rplY 5' UTR revealed an
      important role of the conserved elements in the translation control. Thus, the
      rplY expression regulation represents one more example of regulatory pathways
      that control ribosome biogenesis in Escherichia coli and related bacteria.

PMID- 25749696
TI  - An event-based account of conformity.
AB  - People often change their behavior and beliefs when confronted with deviating
      behavior and beliefs of others, but the mechanisms underlying such phenomena of
      conformity are not well understood. Here we suggest that people cognitively
      represent their own actions and others' actions in comparable ways (theory of
      event coding), so that they may fail to distinguish these two categories of
      actions. If so, other people's actions that have no social meaning should induce
      conformity effects, especially if those actions are similar to one's own actions.
      We found that female participants adjusted their manual judgments of the beauty
      of female faces in the direction consistent with distracting information without
      any social meaning (numbers falling within the range of the judgment scale) and
      that this effect was enhanced when the distracting information was presented in
      movies showing the actual manual decision-making acts. These results confirm that
      similarity between an observed action and one's own action matters. We also found
      that the magnitude of the standard conformity effect was statistically equivalent
      to the movie-induced effect. 

PMID- 25749697
TI  - Improving vision among older adults: behavioral training to improve sight.
AB  - A major problem for the rapidly growing population of older adults (age 65 and
      over) is age-related declines in vision, which have been associated with
      increased risk of falls and vehicle crashes. Research suggests that this
      increased risk is associated with declines in contrast sensitivity and visual
      acuity. We examined whether a perceptual-learning task could be used to improve
      age-related declines in contrast sensitivity. Older and younger adults were
      trained over 7 days using a forced-choice orientation-discrimination task with
      stimuli that varied in contrast with multiple levels of additive noise. Older
      adults performed as well after training as did college-age younger adults prior
      to training. Improvements transferred to performance for an untrained stimulus
      orientation and were not associated with changes in retinal illuminance.
      Improvements in far acuity in younger adults and in near acuity in older adults
      were also found. These findings indicate that behavioral interventions can
      greatly improve visual performance for older adults. 

PMID- 25749698
TI  - Two languages, two minds: flexible cognitive processing driven by language of
      operation.
AB  - People make sense of objects and events around them by classifying them into
      identifiable categories. The extent to which language affects this process has
      been the focus of a long-standing debate: Do different languages cause their
      speakers to behave differently? Here, we show that fluent German-English
      bilinguals categorize motion events according to the grammatical constraints of
      the language in which they operate. First, as predicted from cross-linguistic
      differences in motion encoding, bilingual participants functioning in a German
      testing context prefer to match events on the basis of motion completion to a
      greater extent than do bilingual participants in an English context. Second, when
      bilingual participants experience verbal interference in English, their
      categorization behavior is congruent with that predicted for German; when
      bilingual participants experience verbal interference in German, their
      categorization becomes congruent with that predicted for English. These findings
      show that language effects on cognition are context-bound and transient,
      revealing unprecedented levels of malleability in human cognition. 

PMID- 25749699
TI  - Relevant and robust: a response to Marcus and Davis (2013).

PMID- 25749700
TI  - Gender cognition in transgender children.
AB  - A visible and growing cohort of transgender children in North America live
      according to their expressed gender rather than their natal sex, yet scientific
      research has largely ignored this population. In the current study, we adopted
      methodological advances from social-cognition research to investigate whether 5-
      to 12-year-old prepubescent transgender children (N = 32), who were presenting
      themselves according to their gender identity in everyday life, showed patterns
      of gender cognition more consistent with their expressed gender or their natal
      sex, or instead appeared to be confused about their gender identity. Using
      implicit and explicit measures, we found that transgender children showed a clear
      pattern: They viewed themselves in terms of their expressed gender and showed
      preferences for their expressed gender, with response patterns mirroring those of
      two cisgender (nontransgender) control groups. These results provide evidence
      that, early in development, transgender youth are statistically indistinguishable
      from cisgender children of the same gender identity. 

PMID- 25749701
TI  - Body weight misperception in adolescence and incident obesity in young adulthood.
AB  - Misperceptions of one's weight are common in adolescence. Adolescents of normal
      weight who misperceive themselves as being overweight tend to engage in unhealthy
      dieting practices and behaviors that are conducive to obesity. To examine whether
      this misperception is associated with a risk of obesity during early adulthood,
      we analyzed data from the National Longitudinal Study of Adolescent Health (N =
      6,523; mean age at baseline = 16 years; 58% female). Adolescents who misperceived
      themselves as being overweight had greater odds of becoming obese over the 12
      year follow-up period than adolescents who perceived their weight accurately
      (odds ratio = 1.41, 95% confidence interval = [1.22, 1.64]). Although the
      increase in the odds associated with misperception of weight was apparent for
      both sexes, it was significantly stronger among boys (1.89 greater odds) than
      among girls (1.29 greater odds). The present research indicates that weight-based
      self-stigmatization, much like weight-based social stigmatization, is a powerful
      risk factor for incident obesity. This finding underscores the importance of
      addressing inaccurate body weight perceptions, even among adolescents of normal
      weight. 

PMID- 25749702
TI  - How do stereotypes influence choice?
AB  - In the study reported here, I tracked one process through which stereotypes
      affect choice. The Implicit Association Test (IAT) and a measurement of
      predecisional information distortion were used to assess the influence of the
      association between male gender and career on the evaluation of information
      related to the job performance of stereotypical targets (male) and
      nonstereotypical targets (female). When the IAT revealed a strong association
      between male gender and career and the installed leader in the choice process was
      a stereotypical target, decision makers supported the leader with more proleader
      distortion; when the IAT revealed a strong association between male gender and
      career and the installed leader in the choice process was a nonstereotypical
      target, decision makers supported the trailer with less antitrailer distortion. A
      stronger association between male gender and career therefore resulted in an
      upward shift of the evaluation related to the stereotypical target (both as a
      trailer and a leader), which subsequently biased choice. 

PMID- 25749703
TI  - Still searching for principles: a response to Goodman et al. (2015).

PMID- 25749704
TI  - Narrating the generative life.
AB  - Generativity is an adult's concern for and commitment to promoting the well-being
      of future generations. Analyzing lengthy life-narrative interviews of late
      midlife adults, we examined the extent to which a particular kind of life story
      is empirically linked to self-report measures of generativity and other indices
      of psychosocial adaptation in midlife. The results showed that highly generative
      adults are significantly more likely than their less-generative counterparts to
      construe their lives as variations on a prototypical redemption narrative,
      wherein the story's protagonist (a) enjoys an early advantage in life, (b)
      exhibits sensitivity to the suffering of other people, (c) develops a clear moral
      framework, (d) repeatedly transforms negative scenes into positive outcomes, and
      (e) pursues prosocial goals for the future. The psychological and cultural
      features of redemptive life stories are considered, as are the problems and
      potentialities of life-narrative research in psychological science. 

PMID- 25749705
TI  - Selection and characterization of camelid nanobodies towards urokinase-type
      plasminogen activator.
AB  - Urokinase-type plasminogen activator (uPA) is a trypsin-like serine protease that
      plays a vital role in extracellular conversion of inactive plasminogen into
      catalytically active plasmin. Activated plasmin facilitates the release of
      several proteolytic enzymes, which control processes like pericellular
      proteolysis and remodeling of ECM. uPA and the receptor uPAR, are overexpressed
      in a number of malignant tumours and uPA/uPAR play major roles in adhesion,
      migration, invasion and metastasis of cancer cells. Elevated levels of uPA have
      been reported as a risk biomarker for disease relapse, increased cancer
      malignancy and poor survival prognosis. For these reasons uPA is considered an
      important target for anticancer drug therapy. In this study we isolated two camel
      single domain antibodies (nanobodies) from a naive library by phage display. The
      nanobody sequences were sequence-optimized for Escherichia coli expression,
      cloned into the pET22-B(+) vector system, expressed in BL-21 cells and purified
      from the periplasmic fraction by IMAC. ELISA tests demonstrated that the purified
      nanobodies were specific for uPA when tested towards other trypsin-like serine
      proteases. The apparent affinities of the nanobodies were determined by
      competitive ELISA to 80 nM and 522 nM, respectively. The best binder did not
      inhibit uPA (nAb-C3), however the lowest affinity binder (nAb-C8) was able to
      inhibit the uPA-mediated cleavage of the substrate S-2444. The results validate
      the naive library as a resource for retrieval of relevant lead molecules and the
      novel uPA-nanobodies can be useful pharmacological tools to study uPA structure
      function relationships.

PMID- 25749706
TI  - Molecular characterization of the liver-expressed antimicrobial peptide 2 (LEAP
      2) in a teleost fish, Plecoglossus altivelis: antimicrobial activity and
      molecular mechanism.
AB  - Liver-expressed antimicrobial peptide 2 (LEAP-2) is widespread in fish and plays
      an important role in the host's innate immune system. In this study, full-length
      cDNA for LEAP-2 (PaLEAP-2) gene was cloned and sequenced from ayu, Plecoglossus
      altivelis. PaLEAP-2 mRNA was detected in a wide range of tissues, with the
      highest level of transcripts found in the liver. Upon induction by Vibrio
      anguillarum, its expression significantly increased in the liver, kidney, spleen,
      gill, and heart, but decreased in the intestine. The PaLEAP-2 mature peptide was
      chemically synthesized; it exhibited selective antimicrobial activity against
      various bacteria in vitro. PaLEAP-2 at high concentration reduced the bacterial
      load and improved the survival rate of V. anguillarum-infected ayu. Moreover, it
      inhibited the expression of mRNAs for TNF-alpha and IL-1beta in V. anguillarum
      infected ayu, both at high and low concentrations. PaLEAP-2 induced hydrolysis of
      the pET-22b plasmid DNA and bacterium genomic DNA. These results suggest that
      PaLEAP-2 plays a role in ayu immune responses against bacterial infection. 

PMID- 25749707
TI  - An immunoproteomic approach for characterization of dormancy within
      Staphylococcus epidermidis biofilms.
AB  - Virulence of Staphylococcus epidermidis is mainly attributed to surface
      colonization and biofilm formation in indwelling medical devices. Physiological
      heterogeneity of biofilms may influence host immune response and sensitivity to
      antibiotics. Dormant cells, among others, contribute to biofilm heterogeneity.
      The aim of this study was to identify immunogenic proteins of S. epidermidis
      biofilms associated with dormancy mechanism, by using two-dimensional
      electrophoresis (2-DE) immunoblotting and mass spectrometry (MS). A total of 19
      bacterial proteins, recognized by human serum samples, were identified. These
      proteins were mainly involved in small molecule metabolic biological processes.
      Catalytic activity and ion binding were the most representative molecular
      functions. CodY and GpmA proteins were more reactive to sera when biofilm
      dormancy was induced, while FtnA and ClpP were more reactive when dormancy was
      prevented. This is the first work that identifies differences in immunoreactive
      proteins within bacterial biofilms with induced or prevented dormancy.
      Considering the importance of dormancy within biofilms, further evaluation of
      these proteins can provide insights into the mechanisms related to dormancy and
      help to improve current understanding on how dormancy affects the host immune
      response. 

PMID- 25749708
TI  - Skeletal muscle quantitative nuclear magnetic resonance imaging follow-up of
      adult Pompe patients.
AB  - Adult late-onset Pompe disease is most often a slowly progressive limb-girdle and
      spine extensor muscle dystrophy, due to defective lysosomal acid maltase. With
      the exception of the few patients who present with a dramatically accelerated
      clinical course, standard diagnostic imaging fail to detect and evaluate disease
      progression between two successive visits. In muscle dystrophy of very rapid
      evolution, like the Duchenne disease, quantitative NMR imaging has successfully
      demonstrated its capacity to objectivate both disease activity and degenerative
      changes progression over short follow-up periods. The purpose of this
      retrospective monocentric open-label study was to investigate whether
      quantitative NMR imaging can monitor disease progression in adult Pompe patients
      despite its very slow nature. Quantitative imaging of Pompe patients succeeded in
      demonstrating that muscle fatty infiltration increased on average by 0.9%/year,
      with the hamstring and adductor muscles showing the fastest degradation. Muscle
      water T2 mapping revealed that 32% of all muscles had abnormally high T2 in at
      least one of two successive examinations. When muscle water T2 was abnormal,
      fatty degenerative changes were further increased by 0.61%/year. Enzyme
      replacement therapy resulted in 0.68%/year slowdown of the muscle fatty
      infiltration, in both muscles with normal and high T2s.

PMID- 25749709
TI  - Staphylococcus epidermidis serine--aspartate repeat protein G (SdrG) binds to
      osteoblast integrin alpha V beta 3.
AB  - Staphylococcus epidermidis is the leading etiologic agent of orthopaedic implant
      infection. Contamination of the implanted device during insertion allows bacteria
      gain entry into the sterile bone environment leading to condition known as
      osteomyelitis. Osteomyelitis is characterised by weakened bones associated with
      progressive bone loss. The mechanism through which S. epidermidis interacts with
      bone cells to cause osteomyelitis is poorly understood. We demonstrate here that
      S. epidermidis can bind to osteoblasts in the absence of matrix proteins. S.
      epidermidis strains lacking the cell wall protein SdrG had a significantly
      reduced ability to bind to osteoblasts. Consistent with this, expression of SdrG
      in Lactococcus lactis resulted in significantly increased binding to the
      osteoblasts. Protein analysis identified that SdrG contains a potential integrin
      recognition motif. alphaVbeta3 is a major integrin expressed on osteoblasts and
      typically recognises RGD motifs in its ligands. Our results demonstrate that S.
      epidermidis binds to recombinant purified alphaVbeta3, and that a mutant lacking
      SdrG failed to bind. Blocking alphaVbeta3 on osteoblasts significantly reduced
      binding to S. epidermidis. These studies are the first to identify a mechanism
      through which S. epidermidis binds to osteoblasts and potentially offers a
      mechanism through which implant infection caused by S. epidermidis leads to
      osteomyelitis. 

PMID- 25749710
TI  - Staphylococcus aureus dry stress survivors have a heritable fitness advantage in
      subsequent dry exposure.
AB  - Staphylococcus aureus is a major cause of hospital-acquired infections. The
      ability to survive on abiotic surfaces is an important characteristic that
      facilitates transmission between human hosts. We found that S. aureus survivors
      of dry surface incubation are resistant to subsequent dry stress exposure.
      Survivors also had reduced sensitivity to the disinfectant chlorhexidine
      gluconate, but not to ethanol. By using a set of mutants in cardiolipin synthase
      genes, we further demonstrated that the housekeeping cardiolipin synthase, Cls2,
      was significant for survival on dry surface. Taken together, this study provides
      insights into S. aureus survival outside of a host. 

PMID- 25749711
TI  - Reliability of modified sensory interaction test as measured with force platform.
AB  - The test-retest reliability of the modified sensory interaction test on a force
      platform was performed in a group of 26 young and 15 elderly females for four
      sensory conditions: standing on firm and compliant surface with eyes open and
      closed. The test-retest reliability was good to excellent in both groups, with
      higher level of test-retest reliability in more demanding conditions. The most
      reliable time-domain variables for standing on firm surface with eyes open were:
      sway area from principal components (ICC = 0.77) for young and mean velocity,
      medio-lateral and total path lengths (ICC = 0.91) for elderly. For eyes closed,
      the most reliable variables were antero-posterior path length and sway area
      calculated by Fourier coefficients (ICC = 0.85) for young and medio-lateral path
      length (ICC = 0.93) for elderly. For compliant surface with open eyes, the most
      reliable variable was medio-lateral variability (ICC = 0.83) for young and total
      path length and mean velocity (ICC = 0.92) for elderly participants, whereas for
      eyes closed the most reliable variables were mean velocity, total and medio
      lateral path lengths for young, and mean velocity for elderly group, all with ICC
      = 0.90. Modified sensory interaction test is therefore a reliable measure for
      balance and could be recommended as an outcome measure for balance retraining
      programmes. 

PMID- 25749712
TI  - Direct and indirect costs associated with ankylosing spondylitis and related
      disease activity scores in Turkey.
AB  - This study assessed quality of life, direct and indirect healthcare costs related
      to ankylosing spondylitis (AS). This study included 650 prevalent AS patients
      visiting seven centers at tertiary healthcare institutions in Turkey who were
      interviewed using a standard questionnaire to determine annual direct and
      indirect healthcare costs. Eligible patients were age >=18 years with AS for at
      least 12 months. Direct costs were categorized as inpatient, outpatient and
      pharmacy, and AS-related consultation. Indirect costs were categorized as workday
      loss, additional AS-related costs, and caregiver costs. Clinical outcome measures
      were obtained, including Patients' Global Disease Activity (Pt-GDA); visual
      analog scale (Pain-VAS) for pain; Bath Ankylosing Spondylitis Disease Activity
      Index (BASDAI), Functional Index (BASFI), and Metrology Index (BASMI) scores, and
      EuroQoL 5 dimension (EQ-5D) health status survey scores. Mean (?,335.20) and
      median (?5,671.00) annual costs per patient were calculated. Pharmacy costs
      (?4,032.73) were highest among overall expenditures, followed by additional AS
      related consultation (?2,480.38), outpatient (?225.02), and inpatient costs
      (?29.98). Over half of AS patients (54.8 %) experienced work loss. Related
      average annual costs were ?414.16, based on income level. 10.3 % of AS patients
      incurred an additional ?2,008.07 in 1 year. 6.8 % of patients required caregivers
      and incurred ?778.70 in average annual patient paid costs. Mean Pt-GDA, Pain-VAS,
      EQ-5D, BASDAI, BASFI, and BASMI scores were 4.4, 40.5, 62.7, 3.6, 3.1, and 2.9,
      respectively. Direct and indirect AS-related costs are high and represent a
      considerable economic burden on Turkish AS patients.

PMID- 25749713
TI  - Brief Report: A Longitudinal Study of Excessive Smiling and Laughing in Children
      with Angelman Syndrome.
AB  - Elevated laughing and smiling is a key characteristic of the Angelman syndrome
      behavioral phenotype, with cross-sectional studies reporting changes with
      environment and age. This study compares levels of laughing and smiling in 12
      participants across three experimental conditions [full social interaction (with
      eye contact), social interaction with no eye contact, proximity only] at two data
      points. No differences were noted in frequency of laughing and smiling over time
      in any condition. However, with age as a covariate, the frequency of laughing and
      smiling decreased over time in the full social interaction (with eye contact)
      condition only. As this is the first longitudinal study to explore these
      behaviors in Angelman syndrome, the results suggest a gene-environment-time
      interaction within the behavioral phenotype. 

PMID- 25749714
TI  - Characteristics and trends of psychosomatic medicine in top mainstream medical
      journals.

PMID- 25749715
TI  - Factitious mastectomy and hysterectomy: the importance of staying abreast of the
      medical record.

PMID- 25749716
TI  - Comment on "metabolic syndrome and elevated C-reactive protein levels in elderly
      patients with newly diagnosed depression".

PMID- 25749717
TI  - Multidisciplinary team meetings in urogynaecology.
AB  - INTRODUCTION AND HYPOTHESIS: The concept of multidisciplinary team (MDT) is well
      accepted in the current National Health Service (NHS) and is considered good
      practice for the management of chronic conditions. There has been a recent drive
      to have MDTs in managing women with incontinence and complex prolapse as a result
      of recommendations by National Institute for Health and Care Excellence (NICE)
      guidance, Medicines and Healthcare Products Regulatory Agency (MHRA) etc.
      Currently, there are no data on the outcome of case discussion at urogynaecology
      MDTs. The aim of this study was to review the clinical impact of discussion of a
      select group of cases at an urogynaecology MDT and review the clinical literature
      to justify the MDT approach. METHODS: MDT proformas of cases discussed from
      October 2012 to December 2013 were reviewed. Outcomes of the MDT were compared
      with recommendations at the initial consultation. This included change in
      management plan, type of surgery and surgeon as well as time delay due to MDT
      discussion. RESULTS: One hundred six proformas were available for analysis. Age
      range was 23-89 (58) years. Average time from clinic visit to MDT discussion was
      8.32 + 5.9 days. The MDT recommended a change in management plan in 31 cases
      (29.3%), with 11 cases (10.4%) resulting in alternative surgery and 1 case (0.9%)
      with an alternative surgeon. In 18.5% of cases, MDT discussion formulated the
      initial management plan. CONCLUSIONS: Case discussions at our MDT provide an
      effective clinical forum to formulate management plans for complex cases. The
      decision-making process is made robust, without significant impact on waiting
      time. Investment in setting up MDTs has financial implications but provides
      patient benefit.

PMID- 25749718
TI  - Weight loss at the first month of palliative chemotherapy predicts survival
      outcomes in patients with advanced gastric cancer.
AB  - BACKGROUND: Weight loss during chemotherapy is a significant prognostic factor
      for poor survival in patients with advanced gastric cancer (AGC). However, in
      most studies, weight loss was measured at the end of chemotherapy, limiting its
      clinical use. In this study, we evaluated whether weight loss during the first
      month of chemotherapy could predict survival outcomes in patients with AGC.
      METHODS: We analyzed 719 patients with metastatic or recurrent AGC who were
      receiving palliative chemotherapy. We calculated the initial body mass index
      (BMIi), percent weight loss after 1 month of chemotherapy (DeltaW 1m), percent
      weight loss after last administration of chemotherapy (DeltaW end), and average
      weight loss per month during chemotherapy (DeltaW/m). We correlated these data
      with overall survival (OS) by receiver-operating characteristic (ROC) curves and
      Kaplan-Meier curves, and performed a subgroup analysis using Cox regression.
      RESULTS: The probabilities of longer OS had stronger correlations with DeltaW/m
      and DeltaW 1m than with DeltaW end or BMIi. A significant positive correlation
      between DeltaW 1m and DeltaW/m (r (2) = 0.591, p < 0.001) was observed. Median OS
      of patients with DeltaW 1m more than 3 % was significantly shorter than in
      patients with less weight loss (OS: 9.7 vs. 16.3 months, p < 0.001). Subgroup
      analysis revealed that DeltaW 1m accompanied poor survival irrespective of other
      clinical characteristics. CONCLUSION: Weight loss at the very first month of
      palliative chemotherapy could predict unfavorable survival outcomes in AGC.

PMID- 25749720
TI  - Relationship between mean platelet volume and retinopathy of prematurity.
AB  - PURPOSE: We aimed to investigate the association between mean platelet volume
      (MPV) and the occurrence of type 1 retinopathy of prematurity (ROP). MATERIALS
      AND METHODS: This was a retrospective case-control study. Cases with ROP required
      laser surgery; controls developed no ROP or stage 1 ROP. Most recent peripheral
      blood platelet indices before laser (case) and matched age (control) were
      abstracted. Student's t-test and multivariate logistic regression analysis were
      used. RESULTS: A significant difference was found in MPV values between infants
      with ROP and control groups (10.76 +/- 1.27 fl, 10.04 +/- 0.91 fl, p = 0.0001).
      No significant differences were found in the mean platelet counts or MPV/Platelet
      counts between the two groups (p = 0.4151, p = 0.1460, respectively). There was a
      1.94-fold increase in the risk of retinopathy of prematurity (OR:1.94; p = 0.005)
      as the MPV value increased. CONCLUSIONS: Elevated MPV is associated with the
      occurrence of type 1 ROP. A hypothesis is presented concerning the role of
      platelets as sequester and deliverer angiogenesis regulators during the
      neovascularization phase of ROP.

PMID- 25749719
TI  - The RUNX1-PU.1 axis in the control of hematopoiesis.
AB  - The differentiation from multipotent hematopoietic stem cells (HSC) to mature and
      functional blood cells requires the finely tuned regulation of gene expression at
      each stage of development. Specific transcription factors play a key role in this
      process as they modulate the expression of their target genes in an exquisitely
      lineage-specific manner. A large number of important transcriptional regulators
      have been identified which establish and maintain specific gene expression
      patterns during hematopoietic development. Hematopoiesis is therefore a paradigm
      for investigating how transcription factors function in mammalian cells, thanks
      also to the evolution of genome-wide and the next-generation sequencing
      technologies. In this review, we focus on the current knowledge of the biological
      and functional properties of the hematopoietic master regulator RUNX1 (also known
      as AML1, CBFA2, PEBP2aB) transcription factor and its main downstream target
      PU.1. We will outline their relationship in determining the fate of the myeloid
      lineage during normal stem cell development and under conditions when
      hematopoietic development is subverted by leukemic transformation. 

PMID- 25749721
TI  - Change in vision after retinal pigment epithelium tear following the use of anti
      VEGF therapy for age-related macular degeneration.
AB  - PURPOSE: We investigated visual acuity outcomes and their associations in the
      setting of retinal pigment epithelium tear (RPET) following the use of anti
      vascular endothelial growth factor (anti-VEGF) agents. METHODS: This
      retrospective review included all patients treated for neovascular age-related
      macular degeneration (AMD) with an anti-VEGF agent who subsequently developed an
      RPET. All patients who developed an RPET were identified and outcome measures
      data were recorded and analysed. The main outcome measures were best corrected
      visual acuity (BCVA) and spectral domain optical coherence tomography
      characteristics. RESULTS: Among the 14 participants identified, a subfoveal RPET
      was associated with the loss of one or more lines of vision from baseline (p =
      0.03). There was no association between the size of the RPET and BCVA at the time
      of the RPET or final BCVA. The development of a disciform scar was associated
      both with a BCVA at the time of the RPET of < 6/24 (p = 0.02) and a final BCVA of
      < 6/24 (p = 0.02). Ongoing treatment with an anti-VEGF agent following an RPET
      saw five patients (35.7 %) have an improvement in their BCVA and all patients
      maintained their BCVA following the RPET with ongoing anti-VEGF treatment.
      CONCLUSIONS: Visual decline following an RPET is associated with subfoveal
      location of the RPET (p = 0.03) and later development of a disciform scar. These
      data also suggest that the ongoing use of an anti-VEGF agent may stabilise vision
      in some patients following an RPET and for some patients there may be an
      improvement in visual acuity despite the RPET, depending on its location.

PMID- 25749722
TI  - Computational approaches for pharmacovigilance signal detection: toward
      integrated and semantically-enriched frameworks.
AB  - Computational signal detection constitutes a key element of postmarketing drug
      monitoring and surveillance. Diverse data sources are considered within the
      'search space' of pharmacovigilance scientists, and respective data analysis
      methods are employed, all with their qualities and shortcomings, towards more
      timely and accurate signal detection. Recent systematic comparative studies
      highlighted not only event-based and data-source-based differential performance
      across methods but also their complementarity. These findings reinforce the
      arguments for exploiting all possible information sources for drug safety and the
      parallel use of multiple signal detection methods. Combinatorial signal detection
      has been pursued in few studies up to now, employing a rather limited number of
      methods and data sources but illustrating well-promising outcomes. However, the
      large-scale realization of this approach requires systematic frameworks to
      address the challenges of the concurrent analysis setting. In this paper, we
      argue that semantic technologies provide the means to address some of these
      challenges, and we particularly highlight their contribution in (a) annotating
      data sources and analysis methods with quality attributes to facilitate their
      selection given the analysis scope; (b) consistently defining study parameters
      such as health outcomes and drugs of interest, and providing guidance for study
      setup; (c) expressing analysis outcomes in a common format enabling data sharing
      and systematic comparisons; and (d) assessing/supporting the novelty of the
      aggregated outcomes through access to reference knowledge sources related to drug
      safety. A semantically-enriched framework can facilitate seamless access and use
      of different data sources and computational methods in an integrated fashion,
      bringing a new perspective for large-scale, knowledge-intensive signal detection.

PMID- 25749723
TI  - Comprehensive care in gynecologic oncology: The importance of palliative care.

PMID- 25749724
TI  - Seven years follow-up for total lumbar facet joint replacement (TOPS) in the
      management of lumbar spinal stenosis and degenerative spondylolisthesis.
AB  - PURPOSE: To evaluate the feasibility and clinical improvement of a total
      posterior arthroplasty system in the surgical management of lumbar degenerative
      spondylolisthesis and or spinal stenosis. METHODS: During a 1-year period (June
      2006 to July 2007), ten patients were enrolled in a non-randomized prospective
      clinical study. The primary indication was neurogenic claudication due to spinal
      stenosis with single-level degenerative spondylolisthesis. Patients were
      evaluated with X-rays and MRI scans, visual analog scale (VAS) for back and leg
      pain, the Oswestry disability questionnaire, and the SF-36 health survey
      preoperatively, at 6 weeks, 3 months and 6 months and at 1, 2, 3 and 7 years
      postoperatively. RESULTS: The VAS score for back pain dropped from 56.2
      preoperatively to 12.5 at 6 weeks and 19 at 7 years follow-up. The VAS score for
      worse leg pain dropped from 83.5 before surgery to 13 at 6 weeks and 8.8 at 7
      years follow-up. The ODI dropped from 49.1 preoperatively to 13.5 at 6 weeks and
      7.8 at 7 years follow-up. MRI examination at 7 years after surgery did not
      demonstrate stenosis adjacent to the stabilized segment. Spondylolisthesis did
      not progress in any of the cases. One patient had a symptomatic L3-L4 far lateral
      disc herniation 5 years after surgery whose symptoms resolved with non-operative
      treatment. In one patient, conversion to posterolateral fusion was performed due
      to an early device malfunction. CONCLUSION: In patients with spinal stenosis and
      degenerative spondylolisthesis, decompression and posterior arthroplasty with the
      TOPS System can maintain clinical improvement and radiologic stability over time.

PMID- 25749725
TI  - Differentiation of tuberculosis and metastatic cancer in the spine using dynamic
      contrast-enhanced MRI.
AB  - PURPOSE: To investigate the differences between imaging features of spinal
      tuberculosis (TB) and metastatic cancer measured by dynamic contrast-enhanced
      magnetic resonance imaging (DCE-MRI). The presentation of TB on convention MRI
      may not show the typical TB signs, and they may be mis-diagnosed as malignant
      diseases. DCE-MRI may provide additional information to help making differential
      diagnosis. MATERIALS AND METHODS: DCE-MRI was performed in 24 TB and 22
      metastatic cancer patients. The DCE kinetic pattern was determined as "wash-out",
      "plateau" or "persistent enhancement". The characteristic DCE parameters were
      calculated from the signal intensity time course. The two-compartmental
      pharmacokinetic model was used to obtain K (trans), which is the parameter
      associated with the delivery of MR contrast agents into the lesion, and k ep,
      which is the parameter associated with the distribution and clearance of contrast
      agents from the lesion. RESULTS: Of the 24 TB, one case showed the wash-out
      kinetic pattern, 12 cases showed the plateau pattern, and 11 cases showed the
      persistent enhancement pattern. Of the 22 metastatic cancers, 12 cases showed
      wash-out, 7 cases showed plateau, and 3 cases showed persistent enhancement
      patterns. Compared to the metastatic cancer group, the TB group had a lower k ep
      (0.27 +/- 0.15 vs. 0.49 +/- 0.23 min(-1), P < 0.001). The ROC analysis showed
      that the area under the curve was 0.780 for k ep. CONCLUSIONS: DCE-MRI may
      provide additional information for differentiation between spinal TB and
      metastasis, when their manifestations on conventional imaging were similar.

PMID- 25749726
TI  - Cervical spine balance: postoperative radiologic changes in adult scoliosis
      surgery.
AB  - PURPOSE: Cervical spine alignment interests appeared recently and relationships
      between the pelvis and the cervical spine have been reported but remain unclear.
      In this study, postoperative changes for cranial, cervical, lumbar and sagittal
      balance parameters have been measured in adult scoliosis surgery without major
      sagittal malalignment to appreciate the adaptation of the cervical spine.
      METHODS: Twenty-nine consecutive patients with a surgical adult degenerative
      scoliosis treated with a T8-T11 to iliac fusion without PSO or multiple Ponte's
      osteotomies had preoperative and postoperative full spine EOS radiographies to
      measure spino-pelvic parameters. Correlation analysis between the different
      parameters was performed. RESULTS: Lower cervical, lordosis, lumbar lordosis and
      thoracic kyphosis were increased in postoperative as no changes were observed for
      upper cervical lordosis. C1-C7 CL highly correlated (0.85 in preoperative and
      0.87 in postoperative) with C7 slope, which highly correlated itself with global
      balance parameters (0.74 in preoperative and 0.71 in postoperative for CAM-PL)
      underlining the relationship between cervical spine alignment and global
      malalignment. CONCLUSIONS: Modifications of lower CL are observed, as upper CL
      remains constant. If no correlation was found for LL, TK and CL changes, CL
      appears to be highly correlated with C7 slope, which highly correlated itself
      with sagittal global balance parameters. C7 slope appears as a base for CL
      influenced by the spine global alignment.

PMID- 25749727
TI  - Medially misplaced pedicle screws in patients without neurological deficits
      following scoliosis surgery: to observe or to remove?
AB  - PURPOSE: This study investigated whether pedicle screws medially misplaced into
      the spinal canal without neurological complications should be removed or not.
      METHODS: A total of 86 patients with scoliosis that underwent spinal fusion using
      988 pedicle screws were retrospectively reviewed after a minimum follow-up of 2
      years. The inclusion criteria were: (1) patients without outstanding problems
      during the insertion of pedicle screws, (2) patients without neurological
      deficits either intraoperatively or postoperatively, and (3) patients that had
      all implants removed after bone union upon the request of the patient. Medial
      perforations were evaluated using immediate postoperative helical CT images and
      classified into three grades: grade 1 (0-2 mm), grade 2 (2-4 mm), and grade 3
      (over 4 mm). All unexpected events were recorded at the time of removal. RESULTS:
      CT images obtained 2 years postoperatively exhibited neither loosening of screws
      nor pseudoarthrosis in all patients. CSF leakage from screw holes were recognized
      in 3 of 87 medially misplaced screws (3.4 %). There was no CSF leakage in grade 1
      (35 screws), one CSF leakage (2.5 %) in grade 2 (40 screws), and two (16.7 %) in
      grade 3 (12 screws). No neurological abnormalities occurred either
      intraoperatively or postoperatively. CONCLUSION: This study indicated that screws
      medially misplaced at a distance greater than 2 mm, especially 4 mm, may be a
      cause of negative effects on the neural structure and should be removed during
      the early phase of the postoperative period, even among patients without
      postoperative neurological abnormalities.

PMID- 25749728
TI  - The effect of vertebral fracture on the early neurologic recovery in patients
      with central cord syndrome.
AB  - PURPOSE: To compare early changes in the ASIA Motor Score (AMS) between patients
      with central cord syndrome (CCS) from an acute fracture to patients without a
      fracture. METHODS: Patients with CCS were identified and stratified based on the
      presence of a fracture. The AMS through the first week of the patients'
      hospitalization was obtained. Initial injury severity as well as early neurologic
      recovery was measured using the AMS. Analysis of variance was performed to
      determine if age, gender, rectal tone at presentation, congenital stenosis, or
      surgery within 24 h significantly effected the change in AMS. RESULTS: A strong
      trend (p = 0.0504) towards a more severe initial neurologic injury in patients
      with a fracture (AMS 59.7) than in patients without a fracture (AMS 70.2) was
      identified. However, in the week after injury, patients with a fracture had an
      improvement in their neurologic function (DeltaAMS +4.8) while patients without a
      fracture demonstrated neurologic decline (DeltaAMS -5.9). The change in AMS
      between patients with and without a fracture was nearly significant (p = 0.06).
      CONCLUSION: Patients with central cord syndrome present with similar symptoms,
      but injuries with and without a fracture may be associated with a different early
      neurologic recovery. Patients with a fracture have a more severe injury at
      initial presentation, but tend to have neurologic improvement in the first week;
      conversely patients without a fracture have a less severe initial neurologic
      injury, but tend to have a slight decline in neurologic function over the first
      week.

PMID- 25749729
TI  - Influence of the respirator on volatile organic compounds: an animal study in
      rats over 24 hours.
AB  - Long-term animal studies are needed to accomplish measurements of volatile
      organic compounds (VOCs) for medical diagnostics. In order to analyze the time
      course of VOCs, it is necessary to ventilate these animals. Therefore, a total of
      10 male Sprague-Dawley rats were anaesthetized and ventilated with synthetic air
      via tracheotomy for 24 h. An ion mobility spectrometry coupled to multi-capillary
      columns (MCC-IMS) was used to analyze the expired air. To identify background
      contaminations produced by the respirator itself, six comparative measurements
      were conducted with ventilators only. Overall, a number of 37 peaks could be
      detected within the positive mode. According to the ratio peak intensity rat/
      peak intensity ventilator blank, 22 peaks with a ratio >1.5 were defined as
      expired VOCs, 12 peaks with a ratio between 0.5 and 1.5 as unaffected VOCs, and
      three peaks with a ratio <0.5 as resorbed VOCs. The peak intensity of 12 expired
      VOCs changed significantly during the 24 h measurement. These results represent
      the basis for future intervention studies. Notably, online VOC analysis with MCC
      IMS is possible over 24 h in ventilated rats and allows different experimental
      approaches. 

PMID- 25749730
TI  - Populus * canescens grown on Cr-rich tannery waste: Comparison of leaf and root
      biochemical and proteomic responses.
AB  - Treatment of tannery effluents generates large amounts of sediments containing
      concentrated doses of metals (mainly chromium). Such waste is most commonly
      disposed of by landfilling, which is hazardous to the ecosystem due to Cr
      leaching. Afforestation of disposal sites with fast growing trees could stabilize
      contaminants in the soil and prevent them from spreading. The aim of this study
      was to examine the adaptation of Populus * canescens Sm. to tannery waste using
      biochemical and proteomic methods. We analyzed changes in the leaves and fine
      roots of poplar planted in soil or tannery waste. We found no obvious symptoms of
      metal stress, such as: elevated hydrogen peroxide levels or lipid peroxidation,
      but we observed activation of many elements of antioxidative system. Comparison
      of 2-DE protein profiles of leaves and fine roots from poplar grown on soil or
      tannery waste revealed increased expression of glycolytic enzymes and proteins
      involved in the synthesis of cell wall components, changes in the levels of
      proteins associated with photosynthesis, stress-related proteins, proteasome
      subunits and methionine biosynthesis enzymes. This experiment demonstrated that
      proteomic analysis has the potential to link the effects of Cr-rich tannery waste
      with biological consequences.

PMID- 25749731
TI  - Using the quantum yields of photosystem II and the rate of net photosynthesis to
      monitor high irradiance and temperature stress in chrysanthemum (Dendranthema
      grandiflora).
AB  - Under a dynamic greenhouse climate control regime, temperature is adjusted to
      optimise plant physiological responses to prevailing irradiance levels; thus,
      both temperature and irradiance are used by the plant to maximise the rate of
      photosynthesis, assuming other factors are not limiting. The control regime may
      be optimised by monitoring plant responses, and may be promptly adjusted when
      plant performance is affected by extreme microclimatic conditions, such as high
      irradiance or temperature. To determine the stress indicators of plants based on
      their physiological responses, net photosynthesis (Pn) and four chlorophyll-a
      fluorescence parameters: maximum photochemical efficiency of PSII [Fv/Fm],
      electron transport rate [ETR], PSII operating efficiency [F'q/F'm], and non
      photochemical quenching [NPQ] were assessed for potted chrysanthemum
      (Dendranthema grandiflora Tzvelev) 'Coral Charm' under different temperature (20,
      24, 28, 32, 36  degrees C) and daily light integrals (DLI; 11, 20, 31, and 43 mol
      m(-2) created by a PAR of 171, 311, 485 and 667 MUmol m(-2) s(-1) for 16 h). High
      irradiance (667 MUmol m(-2) s(-1)) combined with high temperature (>32  degrees
      C) significantly (p < 0.05) decreased Fv/Fm. Under high irradiance, the maximum
      Pn and ETR were reached at 24  degrees C. Increased irradiance decreased the PSII
      operating efficiency and increased NPQ, while both high irradiance and
      temperature had a significant effect on the PSII operating efficiency at
      temperatures >28  degrees C. Under high irradiance and temperature, changes in
      the NPQ determined the PSII operating efficiency, with no major change in the
      fraction of open PSII centres (qL) (indicating a QA redox state). We conclude
      that 1) chrysanthemum plants cope with excess irradiance by non-radiative
      dissipation or a reversible stress response, with the effect on the Pn and
      quantum yield of PSII remaining low until the temperature reaches 28  degrees C
      and 2) the integration of online measurements to monitor photosynthesis and PSII
      operating efficiency may be used to optimise dynamic greenhouse control regimes
      by detecting plant stress caused by extreme microclimatic conditions.

PMID- 25749732
TI  - Ultraviolet-B protection of ascorbate and tocopherol in plants related with their
      function on the stability on carotenoid and phenylpropanoid compounds.
AB  - Ascorbate and tocopherol are important hydrophilic or lipophilic antioxidants in
      plants, while their crucial roles in the antioxidant defense system under
      ultraviolet B radiation were not well understood. The mutants of Arabidopsis
      thaliana deficient in ascorbate (vtc1 and vtc2) or tocopherol (vte1) were used to
      analyze their physiological, biochemical and metabolic change in responses to
      Ultraviolet B radiation. Results showed that loss of either ascorbate or
      tocopherol caused reduction in phenylpropanoid and flavonol glycosides compounds,
      as well as reduction in superoxide dismutase activity and total cellular
      antioxidant capacity. This ultimately led to higher oxidative stress as well as
      lower levels of photosynthetic pigments (carotenoid and chlorophyll) and CO2
      assimilation rate in the vtc1, vtc2, and vte1 mutants than the wild type under UV
      B radiation, besides unstable early light-induced protein (ELIP1) in those
      mutants. On the other hand, the loss of tocopherol in vte1 mutants was
      compensated by the increase of zeaxanthin and anthocyanin contents, which armed
      vte1 mutants with higher heat dissipation capacity in PS II and higher
      antioxidative capacity than vtc mutants. Consequently the tolerance to UV-B
      radiation were much higher in vte1 mutant than in vtc mutants, furthermore, PS II
      function and light harvesting protein (LHCb1) abundance were reduced only in
      ascorbate-deficient mutant relative to wild type. Our results suggested that the
      ascorbate and tocopherol provided not only direct protective function against UV
      B radiation but also indirect effects by influencing other protective system, in
      particular by affecting the stability of various carotenoid and phenylpropanoid
      compounds.

PMID- 25749733
TI  - A nomogram based on mammary ductoscopic indicators for evaluating the risk of
      breast cancer in intraductal neoplasms with nipple discharge.
AB  - Mammary ductoscopy (MD) is commonly used to detect intraductal lesions associated
      with nipple discharge. This study investigated the relationships between
      ductoscopic image-based indicators and breast cancer risk, and developed a
      nomogram for evaluating breast cancer risk in intraductal neoplasms with nipple
      discharge. A total of 879 consecutive inpatients (916 breasts) with nipple
      discharge who underwent selective duct excision for intraductal neoplasms
      detected by MD from June 2008 to April 2014 were analyzed retrospectively. A
      nomogram was developed using a multivariate logistic regression model based on
      data from a training set (687 cases) and validated in an independent validation
      set (229 cases). A Youden-derived cut-off value was assigned to the nomogram for
      the diagnosis of breast cancer. Color of discharge, location, appearance, and
      surface of neoplasm, and morphology of ductal wall were independent predictors
      for breast cancer in multivariate logistic regression analysis. A nomogram based
      on these predictors performed well. The P value of the Hosmer-Lemeshow test for
      the prediction model was 0.36. Area under the curve values of 0.812 (95 %
      confidence interval (CI) 0.763-0.860) and 0.738 (95 % CI 0.635-0.841) was
      obtained in the training and validation sets, respectively. The accuracies of the
      nomogram for breast cancer diagnosis were 71.2 % in the training set and 75.5 %
      in the validation set. We developed a nomogram for evaluating breast cancer risk
      in intraductal neoplasms with nipple discharge based on MD image findings. This
      model may aid individual risk assessment and guide treatment in clinical
      practice.

PMID- 25749734
TI  - The impact of breast cancer-related lymphedema on the ability to perform upper
      extremity activities of daily living.
AB  - We sought to assess the association of breast cancer-related lymphedema (BCRL)
      with the ability to perform upper extremity activities of daily living (ADL) in
      our patient population. 324 breast cancer patients who had received treatment for
      unilateral breast cancer at our institution between 2005 and 2014 were
      prospectively screened for lymphedema. Bilateral arm measurements were performed
      pre-operatively and during post-operative follow-up using a Perometer. Patients
      completed an extensive quality of life (QOL) questionnaire at the time of each
      study assessment. Lymphedema was defined as a relative volume change (RVC) of
      >=10% from the patient's pre-operative baseline measurement. Linear regression
      models were used to evaluate the relationship between post-operative arm function
      score (as a continuous variable) and RVC, demographic, clinical, and QOL factors.
      By multivariate analysis, greater fear of lymphedema (p < 0.0001), more pain (p <
      0.0001), body mass index >25 (p = 0.0015), mastectomy (p = 0.0001), and having an
      axillary node dissection (p = 0.0045) were all associated with lower functional
      scores. Higher emotional well-being score (p < 0.0001) and adjuvant chemotherapy
      (p = 0.0005) were associated with higher post-operative functional score. Neither
      low-level volume changes (5-10 % RVC) nor BCRL (RVC >=10 %) were associated with
      ability to perform upper extremity ADL as measured by self-report (p = 0.99, p =
      0.79). This prospective study demonstrates that low-level changes in arm volume
      (RVC 5-10 %) as well as clinically significant BCRL (RVC >=10 %) did not impact
      the self-reported ability to use the affected extremity for ADL. These findings
      may help to inform clinicians and patients on the importance of prospective
      screening for lymphedema and QOL which enables early detection and intervention.

PMID- 25749735
TI  - Azithromycin for acute lower respiratory tract infections.
AB  - BACKGROUND: Acute lower respiratory tract infections (LRTI) range from acute
      bronchitis and acute exacerbations of chronic bronchitis to pneumonia.
      Approximately five million people die from acute respiratory tract infections
      annually. Among these, pneumonia represents the most frequent cause of mortality,
      hospitalisation and medical consultation. Azithromycin is a macrolide antibiotic,
      structurally modified from erythromycin and noted for its activity against some
      gram-negative organisms associated with respiratory tract infections,
      particularly Haemophilus influenzae (H. influenzae). OBJECTIVES: To compare the
      effectiveness of azithromycin to amoxycillin or amoxycillin/clavulanic acid
      (amoxyclav) in the treatment of LRTI, in terms of clinical failure, incidence of
      adverse events and microbial eradication. SEARCH METHODS: We searched CENTRAL
      (2014, Issue 10), MEDLINE (January 1966 to October week 4, 2014) and EMBASE
      (January 1974 to November 2014). SELECTION CRITERIA: Randomised controlled trials
      (RCTs) and quasi-RCTs, comparing azithromycin to amoxycillin or
      amoxycillin/clavulanic acid in participants with clinical evidence of an acute
      LRTI, such as acute bronchitis, pneumonia and acute exacerbation of chronic
      bronchitis. DATA COLLECTION AND ANALYSIS: The review authors independently
      assessed all potential studies identified from the searches for methodological
      quality. We extracted and analysed relevant data separately. We resolved
      discrepancies through discussion. We initially pooled all types of acute LRTI in
      the meta-analyses. We investigated the heterogeneity of results using the forest
      plot and Chi(2) test. We also used the index of the I(2) statistic to measure
      inconsistent results among trials. We conducted subgroup and sensitivity
      analyses. MAIN RESULTS: We included 16 trials involving 2648 participants. We
      were able to analyse 15 of the trials with 2496 participants. The pooled analysis
      of all the trials showed that there was no significant difference in the
      incidence of clinical failure on about days 10 to 14 between the two groups (risk
      ratio (RR), random-effects 1.09; 95% confidence interval (CI) 0.64 to 1.85). A
      subgroup analysis in trials with acute bronchitis participants showed
      significantly lower clinical failure in the azithromycin group compared to
      amoxycillin or amoxyclav (RR random-effects 0.63; 95% CI 0.45 to 0.88). A
      sensitivity analysis showed a non-significant reduction in clinical failure in
      azithromycin-treated participants (RR 0.55; 95% CI 0.25 to 1.21) in three
      adequately concealed studies, compared to RR 1.32; 95% CI 0.70 to 2.49 in 12
      studies with inadequate concealment. Twelve trials reported the incidence of
      microbial eradication and there was no significant difference between the two
      groups (RR 0.95; 95% CI 0.87 to 1.03). The reduction of adverse events in the
      azithromycin group was RR 0.76 (95% CI 0.57 to 1.00). AUTHORS' CONCLUSIONS: There
      is unclear evidence that azithromycin is superior to amoxycillin or amoxyclav in
      treating acute LRTI. In patients with acute bronchitis of a suspected bacterial
      cause, azithromycin tends to be more effective in terms of lower incidence of
      treatment failure and adverse events than amoxycillin or amoxyclav. However, most
      studies were of unclear methodological quality and had small sample sizes; future
      trials of high methodological quality and adequate sizes are needed.

PMID- 25749736
TI  - Intergenerational Perspectives on Autonomy Following a Transition to a Continuing
      Care Retirement Community.
AB  - The study evaluated the concept of autonomy from the perspective of older adults
      and their adult children following a transition of the older adult to a
      continuing care retirement community (CCRC). Overall, 70 interviews (with older
      adults and their adult children; 34 dyads) were analyzed, using a line-by-line
      open coding, followed by dyadic analysis. Autonomy was not portrayed as a
      uniform, homogenous construct, but rather encompassed four different domains: (a)
      the focus of one's attention or concerns: on others, on self, or not at all; (b)
      the ability to exercise decisions and make independent choices; (c) the degree of
      physical functioning and ability of the older adult; and (d) the financial
      ability of the older adult. The duality in the relationships between older adults
      and their adult children is discussed in relation to the give and take of
      autonomy that occur following a transition to a CCRC. 

PMID- 25749738
TI  - Writing Prozak Diaries in Tehran: Generational Anomie and Psychiatric
      Subjectivities.
AB  - I explore the historical and cultural shifts that underlie the normalization of
      the term depreshen and the emergence of public psychiatric discourses in 1990s
      Iran. I do this by investigating the cultural sensibilities of a particular
      generation, the self-identified 1980s generation, and the ways they situate what
      is perceived as depreshen in social anomie and the memories of the Iran-Iraq war.
      I argue that psychiatrization of psychological distress in Iran was not simply a
      de-politicizing hegemonic biomedical discourse, but that the contemporary Iranian
      discourses of psychological pathology and social loss evolved in public, hand-in
      hand, through the medicalization of post-war loss. Psychiatric subjectivity
      describes conditions where individuals internalize psychiatry as a mode of
      thinking, and performatively articulate not only their desires, hopes, and
      anxieties, but also historical losses as embodied in individual and collective
      brains. I underscore my interlocutors' simultaneous historicization and
      medicalization of their depreshen, arguing that psychiatrically medicalized
      individuals are performative actors in the discursive formation of both
      biomedical and social truth. Depreshen, in the larger sense of the word, has
      become one way to navigate ruptured pasts, slippery presents, and uncertain
      futures. 

PMID- 25749737
TI  - Polymorphisms in the AOX2 gene are associated with the rooting ability of olive
      cuttings.
AB  - KEY MESSAGE: Different rooting ability candidate genes were tested on an olive
      cross progeny. Our results demonstrated that only the AOX2 gene was strongly
      induced. OeAOX2 was fully characterised and correlated to phenotypical traits.
      The formation of adventitious roots is a key step in the vegetative propagation
      of trees crop species, and this ability is under strict genetic control. While
      numerous studies have been carried out to identify genes controlling adventitious
      root formation, only a few loci have been characterised. In this work, candidate
      genes that were putatively involved in rooting ability were identified in olive
      (Olea europaea L.) by similarity with orthologs identified in other plant
      species. The mRNA levels of these genes were analysed by real-time PCR during
      root induction in high- (HR) and low-rooting (LR) individuals. Interestingly,
      alternative oxidase 2 (AOX2), which was previously reported to be a functional
      marker for rooting in olive cuttings, showed a strong induction in HR
      individuals. From the OeAOX2 full-length gene, alleles and effective
      polymorphisms were distinguished and analysed in the cross progeny, which were
      segregated based on rooting. The results revealed a possible correlation between
      two single nucleotide polymorphisms of OeAOX2 gene and rooting ability.

PMID- 25749739
TI  - Reactive Oxygen Species (ROS) in human semen: determination of a reference range.
AB  - PURPOSE: High levels of reactive oxygen species (ROS) are a leading cause of male
      factor infertility. Measurement of ROS has been hampered by a lack of
      standardisation and confounding variables including choice of controls and sample
      selection. This study aimed to determine a reference range for ROS in human
      semen. METHODS: Semen samples were obtained from men attending for routine semen
      analysis who gave informed consent for the study. Samples were assigned groups:
      Group 1 (N = 94) normal semen parameters, no leucocytospermia; Group 2 (N = 100)
      abnormal semen parameters, no leucocytospermia; Group 3 (N = 41) any semen
      parameters with leucocytospermia. ROS levels were assayed in fresh neat semen
      using a chemiluminescence assay measured in a single tube luminometer. Data are
      reported in relative light units (RLU)/sec/10(6) sperm RESULTS: ROS levels were
      significantly different between Groups 1, 2 and 3 (19.75 +/- 8.12, 95.03 +/-
      33.63, 890.17 +/- 310.23 RLU/sec/10(6) sperm respectively; p < 0.001). Group 3
      gave the highest value confirming this group as the optimum choice for positive
      controls. The reference range < 24.1 RLU/sec/10(6) sperm was determined by ROC
      analysis that differentiates a reference population (Group 1) from a positive
      control group (Group 3), optimising the sensitivity and specificity (80.5 and
      87.2% respectively) of the test. CONCLUSIONS: We have determined a reference
      range for ROS in human semen and identified a patient population that falls
      outside the normal range. This simple, cost effective assay can be incorporated
      into routine diagnostic testing to aid in the diagnosis of male infertility,
      especially with regard to unexplained infertility.

PMID- 25749740
TI  - Endpoint comparison for bone mineral density measurements in North Central Cancer
      Treatment Group cancer clinical trials N02C1 and N03CC (Alliance).
AB  - Bone mineral density (BMD) measurement can vary depending upon anatomical site,
      machine, and normative values used. This analysis compared different BMD
      endpoints in two clinical trials. Trial results differed across endpoints. Future
      clinical trials should consider inclusion of multiple endpoints in sensitivity
      analysis to ensure sound overall study conclusions. INTRODUCTION: Methodological
      issues hamper efficacy assessment of osteoporosis prevention agents in cancer
      survivors. Osteoporosis diagnosis can vary depending upon which bone mineral
      density (BMD) anatomical site and machine is used and which set of normative
      values are applied. This analysis compared different endpoints for osteoporosis
      treatment efficacy assessment in two clinical studies. METHODS: Data from North
      Central Cancer Treatment Group phase III clinical trials N02C1 and N03CC
      (Alliance) were employed involving 774 patients each comparing two treatments for
      osteoporosis prevention. Endpoints for three anatomical sites included raw BMD
      score (RawBMD); raw machine-based, sample-standardized, and reference population
      standardized T scores (RawT, TSamp, TRef); and standard normal percentile
      corresponding to the reference population-standardized T score (TPerc). For each,
      treatment arm comparison was carried out using three statistical tests using
      change and percentage change from baseline (CB, %CB) at 1 year. RESULTS: Baseline
      correlations among endpoints ranged from 0.79 to 1.00. RawBMD and TPerc produced
      more statistically significant results (14 and 19 each out of 36 tests) compared
      to RawT (11/36), TSamp (8/36), and TRef (7/36). Spine produced the most
      statistically significant results (26/60) relative to femoral neck (20/60) and
      total hip (13/60). Lastly, CB resulted in 44 statistically significant results
      out of 90 tests, whereas %CB resulted in only 15 significant results.
      CONCLUSIONS: Treatment comparisons and interpretations were different across
      endpoints and anatomical sites. Transforming via sample statistics provided
      similar results as transforming via reference or machine-based norms. However,
      RawBMD and TPerc may be more sensitive to change as clinical trial endpoints.

PMID- 25749741
TI  - Necessity of therapy for post-thyroidectomy hypocalcaemia: a multi-centre
      experience.
AB  - PURPOSE: Hypoparathyroidism is one of the most common and most feared
      complications of total thyroidectomy (TT). The aim of this study is to detect
      possible markers that may facilitate early tracing of hypocalcaemia-prone
      patients in order to reduce clinical cost by optimizing patient discharge and to
      avoid unnecessary treatment. METHODS: Over an 18-month period, 995 patients, 23 %
      male and 77 % female, aged 52.9 +/- 13.4 years, underwent TT in ten Lombardy
      hospitals. The following parameters were analyzed: calcaemia before and 12-24 and
      48 h after surgery, pre- and post-operative parathyroid hormone (PTH) at 24 h and
      pre-operative 25OH vitamin D. RESULTS: Mortality was nil and morbidity was 22.4
      %. Mean 24-h calcaemia and PTH were 2.17 +/- 0.15 mmol/l and 31.81 +/- 20.35
      pg/ml, respectively; mean 24-h PTH decay was 36.7 +/- 34.12 %. Four hundred
      seventy-three (47.5 %) patients were hypocalcaemic at discharge; 142 of whom had
      transient hypoparathyroidism that became permanent in 27. Patients developing
      hypocalcaemia had significantly higher values of PTH and calcium decay. At
      multiple logistic regression, only 24-h calcium decay, PTH drop and the presence
      of symptoms and parathyroid auto-grafting were significantly related to
      hypoparathyroidism. The association of these factors had a 99.2 % negative
      predictive value (NPV) for the development of hypoparathyroidism. A 70 % PTH drop
      had a 93.75 NPV for transient hypoparathyroidism. A 12 % calcaemia decay had a
      95.7 NPV for hypoparathyroidism. CONCLUSIONS: Hypocalcaemic asymptomatic patients
      with less than 70 % PTH and 12 % calcaemia decay may be safely discharged without
      treatment. Symptomatic patients and those with parathyroid grafting should
      receive calcium and vitamin D.

PMID- 25749742
TI  - Musculoskeletal: what is different in children? Playing in "bouncy house":
      injures foot: pain for 1 week.

PMID- 25749743
TI  - The burden of non-adherence to cardiovascular medications among the aging
      population in Australia: a meta-analysis.
AB  - BACKGROUND: Non-adherence to cardiovascular medications is a problem worldwide,
      even in Australia, which has a socialized medical system, Medicare. OBJECTIVE:
      The aim of this systematic review was to evaluate the burden of non-adherence to
      cardiovascular medications and factors thereof in Australia. DATA SOURCES:
      Pubmed, Embase, CINAHL, PsycInfo, Cochrane Library databases were searched.
      ELIGIBILITY CRITERIA: Articles were included if they were in English, peer
      reviewed and provided empirical data on adherence to cardiovascular medication
      for an Australian cohort. METHODS: A meta-analysis of prevalence of medication
      non-adherence using the double arcsine square root transformed proportion was
      undertaken. Studies were pooled in homogenous prevalence groups and factors that
      differed across groups were ascertained. RESULTS: Five studies, including eight
      datasets and 76,867 subjects were analyzed. Three more or less homogenous
      prevalence categories were discernable: low [19 %, 95 % confidence interval (CI)
      15-24], moderate (26 %, 95 % CI 23-29) and high (43 %, 95 % CI 43-44; this was a
      single study) prevalence of non-adherence. There were minimal clear patterns
      across groups in relation to typical factors of non-adherence (patient,
      condition, healthcare system or socioeconomic factors). Measurements used for non
      adherence were similar for six of the eight included datasets, suggesting this
      did not affect prevalence of non-adherence or inclusion in a prevalence group.
      CONCLUSIONS: Non-adherence to cardiovascular medications is a serious problem in
      the aging Australian setting with an overall prevalence of between 14 and 43 %.
      The lack of patterns in the typical factors of non-adherence suggests that
      another factor, such as patients' beliefs about their conditions and medications,
      may be playing a stronger role in their non-adherence than clinical or
      sociodemographic factors. This is an area for further research.

PMID- 25749744
TI  - Recent advances in the developmental aspects of borderline personality disorder.
AB  - The aim of the current paper was to review the most recent advances in the
      developmental aspects of borderline personality disorder (BPD) over the last 3
      years to highlight the most significant trends in the field. In so doing, we
      identify and discuss two exciting new trends: (a) an emphasis on the biological
      basis of adolescent BPD and (b) empirical evidence in support of long-held
      theories of the development of BPD. Together, these trends suggest that for the
      first time, empirical findings are beginning to emerge in support of complex and
      reciprocal biology * environment interactions over time in the development of
      BPD. We discuss the emerging literature and highlight the translational impact of
      this work for the assessment and intervention of adolescent BPD. 

PMID- 25749745
TI  - Assessment of female sexual arousal in forensic populations.
AB  - Sexual offenses cause significant harm to victims, their families, and society as
      a whole and thus are an important social concern. While it is commonly assumed
      that sexual offenses are committed solely by males, research has shown that
      approximately 5 % of sex crimes in the USA and Canada are committed by females.
      Penile plethysmography (PPG) is a method to measure male genital arousal, which
      is commonly used in the assessment and treatment of male sex offenders and men
      with paraphilic sexual interests. Similarly, vaginal photoplethysmography (VPP)
      is a test to measure female genital arousal and is commonly used to assess female
      sexual dysfunctions. Although VPP is currently the most validated method to
      measure genital arousal in women, its use with female sex offenders or females
      with paraphilic sexual interests has been almost nonexistent. One explanation for
      this is that some research has suggested that female genital arousal may not be
      category-specific, meaning that women will respond to any sexual cues, not just
      those involving their preferred sexual interests. However, not all research
      supports this finding. Due to the potential benefits of using VPP in the
      assessment and treatment of female sex offenders or females with paraphilic
      sexual interests, it is important that further research be done before dismissing
      the use of VPP in forensic populations. The purpose of this article is to review
      the current research on VPP and its applicability to female sex offenders and
      females with paraphilic sexual interests. 

PMID- 25749746
TI  - Personality disorders in DSM-5: emerging research on the alternative model.
AB  - The current categorical classification of personality disorders, originally
      introduced in the Diagnostic and Statistical Manual of Mental Disorders (DSM
      III), has been found to suffer from numerous shortcomings that hamper its
      usefulness for research and for clinical application. The Personality and
      Personality Disorders Work Group for DSM-5 was charged with developing an
      alternative model that would address many of these concerns. The developed model
      involved a hybrid dimensional/categorical model that represented personality
      disorders as combinations of core impairments in personality functioning with
      specific configurations of problematic personality traits. The Board of Trustees
      of the American Psychiatric Association did not accept the Task Force
      recommendation to implement this novel approach, and thus this alternative model
      was included in Sect. III of the DSM-5 among concepts requiring additional study.
      This review provides an overview of the emerging research on this alternative
      model, addressing each of the primary components of the model. 

PMID- 25749748
TI  - Psychological mechanisms of effective cognitive-behavioral treatments for PTSD.
AB  - Several psychotherapies have been established as effective treatments for
      posttraumatic stress disorder (PTSD) including prolonged exposure, cognitive
      processing therapy, and cognitive therapy for PTSD. Understanding the key
      mechanisms of these treatments, i.e., how these treatments lead to therapeutic
      benefits, will enable us to maximize the efficacy, effectiveness, and efficiency
      of these therapies. This article provides an overview of the theorized mechanisms
      for each of these treatments, reviews the recent empirical evidence on
      psychological mechanisms of these treatments, discusses the ongoing debates in
      the field, and provides recommendations for future research. Few studies to date
      have examined whether changes in purported treatment mechanisms predict
      subsequent changes in treatment outcomes. Future clinical trials examining
      treatments for PTSD should use study designs that enable researchers to establish
      the temporal precedence of change in treatment mechanisms prior to symptom
      reduction. Moreover, further research is needed that explores the links between
      specific treatment components, underlying change mechanisms, and treatment
      outcomes. 

PMID- 25749747
TI  - Recent advances in neuroimaging to model eating disorder neurobiology.
AB  - The eating disorders (EDs) anorexia nervosa (AN), bulimia nervosa (BN), and binge
      eating disorder (BED) are severe psychiatric disorders with high mortality. There
      are many symptoms, such as food restriction, episodic binge eating, purging, or
      excessive exercise that are either overlapping or lie on opposite ends of a scale
      or spectrum across those disorders. Identifying how specific ED behaviors are
      linked to particular neurobiological mechanisms could help better categorize ED
      subgroups and develop specific treatments. This review provides support from
      recent brain imaging research that brain structure and function measures can be
      linked to disorder-specific biological or behavioral variables, which may help
      distinguish ED subgroups, or find commonalities between them. Brain structure and
      function may therefore be suitable research targets to further study the
      relationship between dimensions of behavior and brain function relevant to EDs
      and beyond the categorical AN, BN, and BED distinctions. 

PMID- 25749749
TI  - Sexual behavior and autism spectrum disorders: an update and discussion.
AB  - In the last few years, we have gained a deeper understanding about sexuality
      among individuals with autism spectrum disorder (ASD). Greater interest in this
      subject and improvements in the empirical study of ASD populations are driving
      this enlightenment. The data is dispelling antiquated notions that ASD
      individuals are asexual, sexually unknowledgeable and inexperienced, and/or
      disinterested in relationships. We still have a ways to go in examining
      paraphilic or deviant arousal sexual behaviors among ASD individuals. This
      manuscript provides an update on sexuality research in ASD in the last few years.
      This is accompanied by a discussion of the paraphilic type sexual behaviors
      observed among some ASD individuals. 

PMID- 25749751
TI  - Psychopharmacological strategies in the management of posttraumatic stress
      disorder (PTSD): what have we learned?
AB  - There have been significant advancements in the pharmacologic management of
      posttraumatic stress disorder (PTSD) in the past two decades. Multisite
      randomized clinical trials (RCTs) have noted the efficacy of selective serotonin
      reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNR
      Is) for PTSD treatment. Unfortunately, there have been no new medications
      approved to treat PTSD in the past 10 years. Although there have been exciting
      new findings in our knowledge of the neurobiology of PTSD, clinical trials
      testing new medications have lagged. This review summarizes recent research that
      builds on the unique pathophysiology of PTSD and suggests ways to move the field
      forward.

PMID- 25749750
TI  - Current considerations regarding food addiction.
AB  - "Food addiction" is an emerging area, and behavioral and biological overlaps have
      been observed between eating and addictive disorders. Potential misconceptions
      about applying an addiction framework to problematic eating behavior may inhibit
      scientific progress. Critiques of "food addiction" that focus on descriptive
      differences between overeating and illicit drugs are similar to early criticisms
      of the addictiveness of tobacco. Although food is necessary for survival, the
      highly processed foods associated with addictive-like eating may provide little
      health benefit. Individual differences are important in determining who develops
      an addiction. If certain foods are addictive, the identification of possible risk
      factors for "food addiction" is an important next step. Not all treatments for
      addiction require abstinence. Addiction interventions that focus on moderation or
      controlled use may lead to novel approaches to treating eating-related problems.
      Finally, addiction-related policies that focus on environmental (instead of
      educational) targets may have a larger public health impact in reducing
      overeating. 

PMID- 25749752
TI  - The distinct prediction standards for radiological assessments associated with
      soft tissue injuries in the acute tibial plateau fracture.
AB  - The goal of this study was to assess the incidence of soft tissue injury in the
      tibial plateau fracture by magnetic resonance image (MRI) and reveal the
      relationship between the articular widening/depression and the risk of meniscus
      and ligament disorder. A total of 54 patients with tibial plateau fracture were
      indicated for operative intervention. Soft tissue injuries were assessed by MRI.
      Meniscus, anterior/posterior cruciate ligaments and medial/lateral collateral
      ligaments injuries on MRI were evaluated. The articular widening/depression was
      measured in picture archiving and communication systems. Schatzker classification
      of fracture types was not significantly associated with soft tissue injuries. The
      rates of soft tissue injury in types IV and II (respectively, 85.7 and 74.1 %)
      were higher than those in other types. The meniscus injury was the most common
      soft tissue damage, and the incidence of meniscus injury was 55.6 %. When LPDCT
      and LPWCT were, respectively, about 7.6 mm and 10.1 mm and LPDX-ray and LPWX-ray,
      respectively, 5.6 and 7.4 mm, more attention should be paid on the collateral and
      cruciate ligament injuries in types I, II and III. Furthermore, when LPWCT and
      LPWX-ray were, respectively, about 10.3 and 8.6 mm, the collateral and cruciate
      ligaments were susceptible to injury in types IV and V. In conclusion, tibial
      plateau fracture can occur high morbidity of soft tissue injury, including
      meniscus and ligament disorder. X-ray and CT scan had different predicting
      standards for soft tissue injury, and the articular widening/depression in the
      tibial plateau was associated with meniscus and ligament injuries.

PMID- 25749753
TI  - Contact between the acetabulum and dome of a Kerboull-type plate influences the
      stress on the plate and screw.
AB  - We used a three-dimensional finite element method to investigate the conditions
      behind the Kerboull-type (KT) dome. The KT plate dome was divided into five
      areas, and 14 models were created to examine different conditions of dome contact
      with the acetabulum. The maximum stress on the KT plate and screws was estimated
      for each model. Furthermore, to investigate the impact of the contact area with
      the acetabulum on the KT plate, a multiple regression analysis was conducted
      using the analysis results. The dome-acetabulum contact area affected the maximum
      equivalent stress on the KT plate; good contact with two specific areas of the
      vertical and horizontal beams (Areas 3 and 5) reduced the maximum equivalent
      stress. The maximum equivalent stress on the hook increased when the hardness of
      the bone representing the acetabulum varied. Thus, we confirmed the technical
      importance of providing a plate with a broad area of appropriate support from the
      bone and cement in the posterior portion of the dome and also proved the
      importance of supporting the area of the plate in the direction of the load at
      the center of the cross-plate and near the hook. 

PMID- 25749754
TI  - Electrochemical sensor system for breath analysis of aldehydes, CO and NO.
AB  - Bulky and hyphenated laboratory-based analytical instrumentation such as gas
      chromatography/mass spectrometry is still required to trace breath biomarkers in
      the low ppbV level. Innovative sensor-based technologies could provide on-site
      and point-of-care (POC) detection of volatile biomarkers such as breath aldehydes
      related to oxidative stress and cancer. An electrochemical sensor system was
      developed for direct detection of the total abundance of aldehydes in exhaled
      breath in the ppbV level and for simultaneous determination of the airway
      inflammation markers carbon monoxide (CO) and nitric oxide (NO). The sensor
      system was tested in vitro with gaseous standard mixtures and in vivo in
      spontaneously breathing patients and under mechanical ventilation in an animal
      model. The sensor system provided in vitro and in vivo detection of trace levels
      of aldehydes, CO and NO. Inertness of the tubing system was important for
      reliable results. Sensitivity of the aldehyde sensor increased with humidity.
      Response time for analysis of breath samples was about 22 s and relative standard
      deviations of sensor amplitudes were <5%. Detection limits in the low ppbV range
      and a linear range of more than two orders of magnitude could be achieved for
      volatile aldehydes. Cross sensitivities were moderate for alcohols such as
      ethanol or isopropanol and negligible for other typical breath volatile organic
      compounds such as acetone, isoprene or propofol. In proof of concept analyses in
      patients suffering from lung cancer and diabetes, aldehyde and CO sensor signals
      differed between the groups. Elevated CO levels indicated previous smoking. In a
      mechanically ventilated pig, continuous monitoring of breath aldehyde
      concentrations in the low ppbV was realized. Cumulative aldehyde measurements may
      add interesting and complementary information to the conventional parameters used
      in clinical breath research. POC applicability, easy handling and low cost of
      sensors facilitate measurements in large patient cohorts.

PMID- 25749755
TI  - The Risk Factors of Lymph Node Metastasis in Early Gastric Cancer.
AB  - Endoscopic mucosal resection (EMR) or endoscopic submucosal dissection (ESD) is
      an effective alternative treatment for early gastric cancer. However, a major
      concern is the likelihood of lymph node metastasis. From December 1987 to
      December 2006, 391 patients who underwent curative surgery for gastric cancer
      with mucosal (T1a, n = 265) or submucosal (T1b, n = 126) invasion and a retrieved
      lymph node number ? 15 were enrolled. The frequency and risk factors of lymph
      node metastasis were analyzed. The frequency of lymph node metastasis was 4.9 %
      in T1a lesions and 21.4 % in T1b lesions. Although the depth of submucosal tumor
      invasion was < 2 mm, there was a 28.6 % chance of lymph node metastasis. A T1b
      lesion, i.e., the width of the submucosal tumor invasion was < 5 mm, resulted in
      fewer lymph node metastases than lesions > 5 mm in width. Multivariate analysis
      demonstrated that Lauren's diffuse type and lymphatic invasion were independent
      risk factors for lymph node metastasis in T1a lesions, while lymphatic invasion
      was the strongest risk factor for lymph node metastasis in T1b lesions. EMR/ESD
      is a good alternative for T1a intestinal type adenocarcinoma without lymphatic
      invasion. Surgical resection is necessary for patients with T1b gastric cancer
      with lymphatic invasion.

PMID- 25749756
TI  - Cognitive impairment and neurogenotoxic effects in rats exposed to low-intensity
      microwave radiation.
AB  - The health hazard of microwave radiation (MWR) has become a recent subject of
      interest as a result of the enormous increase in mobile phone usage. The present
      study aimed to investigate the effects of chronic low-intensity microwave
      exposure on cognitive function, heat shock protein 70 (HSP70), and DNA damage in
      rat brain. Experiments were performed on male Fischer rats exposed to MWR for 180
      days at 3 different frequencies, namely, 900, 1800 MHz, and 2450 MHz. Animals
      were divided into 4 groups: group I: sham exposed; group II: exposed to MWR at
      900 MHz, specific absorption rate (SAR) 5.953 * 10(-4) W/kg; group III: exposed
      to 1800 MHz, SAR 5.835 * 10(-4) W/kg; and group IV: exposed to 2450 MHz, SAR
      6.672 * 10(-4) W/kg. All the rats were tested for cognitive function at the end
      of the exposure period and were subsequently sacrificed to collect brain. Level
      of HSP70 was estimated by enzyme-linked immunotarget assay and DNA damage was
      assessed using alkaline comet assay in all the groups. The results showed
      declined cognitive function, elevated HSP70 level, and DNA damage in the brain of
      microwave-exposed animals. The results indicated that, chronic low-intensity
      microwave exposure in the frequency range of 900 to 2450 MHz may cause hazardous
      effects on the brain.

PMID- 25749757
TI  - Integrative transcriptome-wide analyses reveal critical HER2-regulated mRNAs and
      lincRNAs in HER2+ breast cancer.
AB  - Breast cancer is a major health problem affecting millions of women worldwide.
      Over 200,000 new cases are diagnosed annually in the USA, with approximately
      40,000 of these cases resulting in death. HER2-positive (HER2+) breast tumors,
      representing 20-30 % of early-stage breast cancer diagnoses, are characterized by
      the amplification of the HER2 gene. However, the critical genes and pathways that
      become affected by HER2 amplification in humans are yet to be specifically
      identified. Furthermore, it is yet to be determined if HER2 amplification also
      affects the expression of long intervening non-coding (linc)RNAs, which are
      involved in the epigenetic regulation of gene expression. We examined changes in
      gene expression by next generation RNA sequencing in human tumors pre- and post-
      HER2 inhibition by trastuzumab in vivo, and changes in gene expression in
      response to HER2 knock down in cell culture models. We integrated our results
      with gene expression analysis of HER2+ tumors vs matched normal tissue from The
      Cancer Genome Atlas. The integrative analyses of these datasets led to the
      identification of a small set of mRNAs, and the associated biological pathways
      that become deregulated by HER2 amplification. Furthermore, our analyses
      identified three lincRNAs that become deregulated in response to HER2
      amplification both in vitro and in vivo. Our results should provide the
      foundation for functional studies of these candidate mRNAs and lincRNAs to
      further our understanding of how HER2 amplification results in tumorigenesis.
      Also, the identified lincRNAs could potentially open the door for future RNA
      based biomarkers and therapeutics in HER2+ breast cancer. 

PMID- 25749759
TI  - Allergenic characterization of a novel allergen, homologous to chymotrypsin, from
      german cockroach.
AB  - PURPOSE: Cockroach feces are known to be rich in IgE-reactive components. Various
      protease allergens were identified by proteomic analysis of German cockroach
      fecal extract in a previous study. In this study, we characterized a novel
      allergen, a chymotrypsin-like serine protease. METHODS: A cDNA sequence
      homologous to chymotrypsin was obtained by analysis of German cockroach expressed
      sequence tag (EST) clones. The recombinant chymotrypsins from the German
      cockroach and house dust mite (Der f 6) were expressed in Escherichia coli using
      the pEXP5NT/TOPO vector system, and their allergenicity was investigated by
      ELISA. RESULTS: The deduced amino acid sequence of German cockroach chymotrypsin
      showed 32.7 to 43.1% identity with mite group 3 (trypsin) and group 6
      (chymotrypsin) allergens. Sera from 8 of 28 German cockroach allergy subjects
      (28.6%) showed IgE binding to the recombinant protein. IgE binding to the
      recombinant cockroach chymotrypsin was inhibited by house dust mite chymotrypsin
      Der f 6, while it minimally inhibited the German cockroach whole body extract.
      CONCLUSIONS: A novel allergen homologous to chymotrypsin was identified from the
      German cockroach and was cross-reactive with Der f 6.

PMID- 25749758
TI  - Specific immunotherapy in atopic dermatitis.
AB  - Allergen specific immunotherapy (SIT) using house dust mite (HDM) extracts has
      been performed mainly with patients of asthma and allergic rhinitis. In the
      meanwhile, there has been a long debate on the efficacy of SIT in atopic
      dermatitis (AD) with only a few double-blind placebo-controlled trials. However,
      several randomized controlled trials of SIT in AD revealed significant
      improvement of clinical symptoms and also, positive result was shown by a
      following meta-analysis study of these trials. In order to predict and evaluate
      the treatment outcome, finding a biomarker that can predict treatment responses
      and treatment end-points is critical but it is very challenging at the same time
      due to the complexity of causes and mechanisms of AD. Other considerations
      including standardization of the easiest and safest treatment protocol and
      optimizing the treatment preparations should be studied as well. This review
      summarizes the basics of SIT in AD including the brief mechanisms, treatment
      methods and schedules, and also highlights the clinical efficacy of SIT in AD
      along with mild, controllable adverse reactions. Immunologic effects and studies
      of various biomarkers are also introduced and finally, future considerations with
      upcoming studies on SIT were discussed. 

PMID- 25749760
TI  - Copy number variation burden on asthma subgenome in normal cohorts identifies
      susceptibility markers.
AB  - PURPOSE: Asthma is a complex disease caused by interplay of genes and environment
      on the genome of an individual. Copy number variations (CNVs) are more common
      compared to the other variations that disrupt genome organization. The effect of
      CNVs on asthma subgenome has been less studied compared to studies on the other
      variations. We report the assessments of CNV burden in asthma genes of normal
      cohorts carried out in different geographical areas of the world and discuss the
      relevance of the observation with respect to asthma pathogenesis. METHODS: CNV
      analysis was performed using Affymerix high-resolution arrays, and various
      bioinformatics tools were used to understand the influence of genes on asthma
      pathogenesis. RESULTS: This study identified 61 genes associated with asthma and
      provided various mechanisms and pathways underlying asthma pathogenesis. CCL3L1,
      ADAM8, and MUC5B were the most prevalent asthma genes. Among them, CCL3L1 was
      found across all 12 populations in varying copy number states. This study also
      identified the inheritance of asthma-CNVs from parents to offspring creating the
      latent period for manifestation of asthma. CONCLUSIONS: This study revealed CNV
      burden with varying copy number states and identified susceptibility towards the
      disease manifestation. It can be hypothesized that primary CNVs may not be the
      initiating event in the pathogenesis of asthma and additional preceding mutations
      or CNVs may be required. The initiator or primary CNVs sensitize normal cohorts
      leading to an increased probability of accumulating mutations or exposure to
      allergic stimulating agents that can augment the development of asthma.

PMID- 25749761
TI  - Reliability and validity of a korean version of the leicester cough
      questionnaire.
AB  - PURPOSE: There are no specific tools for measurement of the severity of chronic
      cough in Korea. We developed a Korean version of the Leicester Cough
      Questionnaire (LCQ) and tested its scaling and clinical properties. METHODS: The
      LCQ was adapted for Korean conditions following a forward-backward translation
      procedure. All patients referred to chronic cough clinics at 5 university
      hospitals between May 2011 and October 2013 completed 2 questionnaires, the LCQ
      and the Short-Form 36 (SF-36), upon presentation and completed the LCQ and the
      Global Rating of Change (GRC) upon follow-up visits after 2 or 4 weeks.
      Concurrent validation, internal consistency, repeatability, and responsiveness
      were determined. RESULTS: For the concurrent validation, the correlation
      coefficients (n=202 patients) between the LCQ and SF-36 varied between 0.42 and
      0.58. The internal consistency of the LCQ (n=207) was high for each of the
      domains with a Cronbach's alpha coefficient of 0.82-0.94. The repeatability of
      the LCQ in patients with no change in cough (n=23) was high, with intra-class
      correlation coefficients of 0.66-0.81. Patients who reported an improvement in
      cough (n=30) on follow-up visits demonstrated significant improvement in each of
      the domains of the LCQ. CONCLUSIONS: The Korean version of the LCQ is a valid and
      reliable questionnaire for measurement of the severity of cough in patients with
      chronic cough.

PMID- 25749762
TI  - Association Between PTPN22 Polymorphisms and IgE Responses to Staphylococcal
      Superantigens in Chronic Urticaria.
AB  - Protein tyrosine phosphatase-22 (PTPN22) gene encodes lymphoid-specific tyrosine
      phosphatase (Lyp), an inhibitor of T cell activation. A polymorphism of the
      PTPN22 gene has been found to be associated with chronic urticaria (CU). We
      investigated the associations between PTPN22 gene polymorphisms and CU
      characteristics, including serum specific IgE antibodies response to toxic shock
      syndrome toxin-1 (TSST-1) and staphylococcal enterotoxin A (SEA). CU patients
      (n=409) and normal healthy controls (n=388) were enrolled in the present study.
      Serum specific IgE to TSST-1 and SEA were measured by ImmunoCAP(r). Five PTPN22
      single nucleotide polymorphisms, -1123G>C, 1858C>T, 13145A>G, 14943C>T, and
      20628A>G, were genotyped. There were no significant differences in genotype or
      haplotype frequencies of these polymorphisms between the 2 groups. CU patients
      carrying the GG genotype at 20628A>G (P=0.035) or haplotype 3 [GGG] (P=0.047) had
      a significantly higher prevalence of serum specific IgE to TSST-1 compared to non
      carriers. Similarly, CT/TT genotype at 14943C>T had a significantly higher
      prevalence of serum specific IgE to SEA (P=0.045). The findings suggest that the
      PTPN22 gene polymorphisms at 20628A>G and 14943C>T may enhance serum specific IgE
      responses to TSST-1 and SEA, which may contribute to CU pathogenesis. 

PMID- 25749763
TI  - Immunologic evaluation of patients with cefotetan-induced anaphylaxis.
AB  - Cefotetan is a commonly prescribed second-generation cephalosporin that acts
      against a wide range of bacteria. However, cefotetan-induced hypersensitivity has
      rarely been reported. We report 2 cases of cefotetan-induced anaphylaxis with
      immunologic evaluation. The first case was a 70-year-old asthmatic woman who had
      dyspnea and hypotension during administration of cefotetan, in which high serum
      specific IgE to cefotetan-human serum albumin (HSA) conjugate was detected by
      enzyme-linked immunosorbent assay. The second case was a 63-year-old asthmatic
      woman who complained of chest tightness and dyspnea during cefotetan infusion, in
      which high serum-specific IgG1 and IgG4 with no serum specific IgE to cefotetan
      HSA conjugate was detected. The basophil activation test using basophils from the
      patient showed a significant up-regulation of CD63 with the addition of anti-IgG4
      antibody compared with that in non-atopic healthy controls. In conclusion,
      cefotetan can induce anaphylaxis, which may involve both IgE- and IgG4-mediated
      responses in the pathogenic mechanism. 

PMID- 25749764
TI  - Bee Pollen-Induced Anaphylaxis: A Case Report and Literature Review.
AB  - Bee pollen is pollen granules packed by honey bees and is widely consumed as
      natural healthy supplements. Bee pollen-induced anaphylaxis has rarely been
      reported, and its allergenic components have never been studied. A 40-year-old
      male came to the emergency room with generalized urticaria, facial edema,
      dyspnea, nausea, vomiting, abdominal pain, and diarrhea 1 hour after ingesting
      one tablespoon of bee pollen. Oxygen saturation was 91%. His symptoms resolved
      after injection of epinephrine, chlorpheniramine, and dexamethasone. He had
      seasonal allergic rhinitis in autumn. Microscopic examination of the bee pollen
      revealed Japanese hop, chrysanthemum, ragweed, and dandelion pollens. Skin-prick
      with bee pollen extracts showed positive reactions at 0.1 mg/mL (A/H ratio > 3+).
      Serum specific IgE to ragweed was 25.2, chrysanthemum 20.6, and dandelion 11.4
      kU/L; however, Japanese hop, honey-bee venom and yellow-jacket venom were
      negative (UniCAP(r), Thermo Fisher Scientific, Uppsala, Sweden). Enzyme-linked
      immunosorbent assay (ELISA) confirmed serum specific IgE to bee-pollen extracts,
      and an ELISA inhibition assay for evaluation of cross-allergenicity of bee pollen
      and other weed pollens showed more than 90% of inhibition with chrysanthemum and
      dandelion and ~40% inhibition with ragweed at a concentration of 1 MUg/mL. Sodium
      dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) and IgE-immunoblot
      analysis revealed 9 protein bands (11, 14, 17, 28, 34, 45, 52, 72, and 90 kDa)
      and strong IgE binding at 28-34 kDa, 45 and 52 kDa. In conclusion, healthcare
      providers should be aware of the potential risk of severe allergic reactions upon
      ingestion of bee pollen, especially in patients with pollen allergy. 

PMID- 25749765
TI  - Hypersensitivity Pneumonitis Caused by Cephalosporins With Identical R1 Side
      Chains.
AB  - Drug-induced hypersensitivity pneumonitis results from interactions between
      pharmacologic agents and the human immune system. We describe a 54-year-old man
      with hypersensitivity pneumonitis caused by cephalosporins with identical R1 side
      chains. The patient, who complained of cough with sputum, was prescribed
      ceftriaxone and clarithromycin at a local clinic. The following day, he
      complained of dyspnea, and chest X-ray revealed worsening of inflammation. Upon
      admission to our hospital, antibiotics were changed to cefepime with
      levofloxacin, but his pneumonia appeared to progress. Changing antibiotics to
      meropenem with ciprofloxacin improved his symptoms and radiologic findings.
      Antibiotics were de-escalated to ceftazidime with levofloxacin, and his condition
      improved. During later treatment, he was mistakenly prescribed cefotaxime, which
      led to nausea, vomiting, dyspnea and fever, and indications of pneumonitis on
      chest X-ray. We performed bronchoalveolar lavage, and the findings included
      lymphocytosis (23%), eosinophilia (17%), and a low cluster of differentiation
      (CD) 4 to CD8 ratio (0.1), informing a diagnosis of drug-induced pneumonitis.
      After a medication change, his symptoms improved and he was discharged. One year
      later, he was hospitalized for acute respiratory distress syndrome following
      treatment with ceftriaxone and aminoglycosides for an upper respiratory tract
      infection. After steroid therapy, he recovered completely. In this patient,
      hypersensitivity reaction in the lungs was caused by ceftriaxone, cefotaxime, and
      cefepime, but not by ceftazidime, indicating that the patient's hypersensitivity
      pneumonitis was to the common R1 side chain of the cephalosporins. 

PMID- 25749766
TI  - Basophil Activation Tests Based on CD193 Marker in Dipyrone Allergy.

PMID- 25749767
TI  - Basophil activation tests: a diagnostic break-through in opiate allergy.

PMID- 25749768
TI  - Seven steps to the diagnosis of NSAIDs hypersensitivity: how to apply a new
      classification in real practice?
AB  - Frequent use of non-steroidal anti-inflammatory drugs (NSAIDs) has been
      paralleled by increasing occurrence of adverse reactions, which vary from mild
      local skin rashes or gastric irritation to severe, generalized symptoms and even
      life-threatening anaphylaxis. NSAID-induced hypersensitivity reactions may
      involve both immunological and non-immunological mechanisms and should be
      differentiated from type A adverse reactions. Clinical diagnosis and effective
      management of a hypersensitive patient cannot be achieved without identifying the
      underlying mechanism. In this review, we discuss the current classification of
      NSAID-induced adverse reactions and propose a practical diagnostic algorithm that
      involves 7 steps leading to the determination of the type of NSAID-induced
      hypersensitivity and allows for proper patient management. 

PMID- 25749769
TI  - Local immunoglobulin e in the nasal mucosa: clinical implications.
AB  - Immunoglobulin E (IgE) can be highly elevated in the airway mucosa independently
      of IgE serum levels and atopic status. Mostly, systemic markers are assessed to
      investigate inflammation in airway disease for research or clinical practice. A
      more accurate but more cumbersome approach to determine inflammation at the
      target organ would be to evaluate markers locally. We review evidence for local
      production of IgE in allergic rhinitis (AR) and chronic rhinosinusitis with nasal
      polyps (CRSwNP). Diagnostic and therapeutic consequences in clinical practice are
      discussed. We describe that the airway mucosa has the intrinsic capability to
      produce IgE. Moreover, not only do IgE-positive B cells reside within the mucosa,
      but all tools are present locally for affinity maturation by somatic
      hypermutation (SHM), clonal expansion, and class switch recombination to IgE.
      Recognizing local IgE in the absence of systemic IgE has diagnostic and
      therapeutic consequences. Therefore, we emphasize the importance of local IgE in
      patients with a history of AR or CRSwNP. 

PMID- 25749770
TI  - Novel Risk Factors for Allergic Rhinitis in Korean Elementary School Children:
      ARCO-kids Phase II in a Community.
AB  - PURPOSE: Allergic rhinitis (AR) is a multifactorial disease whose genetic and
      environmental risk factors have been studied for decades. Many pediatric studies
      have pointed out the familial history of allergy, hygiene hypothesis, breast
      feeding, pet ownership, and diets as risk factors of AR. However, most of factors
      are still up for debate. This preliminary report aimed to confirm the known risk
      factors and find the novel risk factors for AR in the Korean pediatric
      population. METHODS: A bi-seasonal, winter and summer, study in 2 elementary
      schools included all students whose parents completed the questionnaire of
      medical and social histories, quality of life, infant and early-childhood
      history, and the living styles. Skin prick tests and endoscopic examinations were
      conducted on all participants. RESULTS: Among total 1,020 children, 338
      participants had AR. The multivariate logistic regression analysis highlighted 6
      factors: male gender (OR, 2.10; 95% CI, 1.32-3.33), older age (1.65; 1.03-2.65),
      previous history of allergic conjunctivitis (14.25; 4.99-40.74), asthma (2.73;
      0.96-7.76) and pneumonia (0.39; 0.19-0.82), and an hour increase in daily playing
      time (0.90; 0.80-1.00). CONCLUSIONS: Lack of pneumonia in early childhood and
      short playing time are newly found risk factors for Korean pediatric AR in this
      study confirming male gender, older age and previous history of allergic
      conjunctivitis and asthma as the risk factors.

PMID- 25749771
TI  - TMEM16A-Mediated Mucin Secretion in IL-13-Induced Nasal Epithelial Cells From
      Chronic Rhinosinusitis Patients.
AB  - PURPOSE: Chronic rhinosinusitis with nasal polyps (CRSwNP), a mainly Th2 cytokine
      mediated disease, often involves mucus secretion. Recent evidence suggests that
      transmembrane protein 16A (TMEM16A), a calcium-activated Cl- channel (CaCC), can
      regulate mucus secretion from airway epithelium by transepithelial electrolyte
      transport and hydration. However, the role of TMEM16A in mucin
      production/secretion in the airway epithelium is not clear. This study was
      conducted to determine the role of TMEM16A in mediating mucin secretion in human
      nasal polyp epithelial cells (HNPECs) induced by IL-13. METHODS: Human sinonasal
      mucosa tissue and dissociated sinonasal epithelium from control subjects and
      patients with CRSwNP were assessed for the expression of TMEM16A and the
      secretion of human mucin 5AC (MUC5AC) by immunohistochemistry, Western blot
      analysis, and enzyme-linked immuno-sorbent assay (ELISA). A model of the Th2
      inflammatory environment was created by exposure of primary air-liquid interface
      (ALI)-cultured HNPECs to interleukin-13 (IL-13) for 14 days, with subsequent
      assessment of TMEM16A expression in cell lysates by Western blotting and MUC5AC
      secretion in apical washings of cells by ELISA. RESULTS: The expressions of
      TMEM16A and MUC5AC were increased in human nasal polyp tissue and dissociated
      nasal polyp epithelium. TMEM16A was detected in IL-13-treated HNPECs,
      specifically in MUC5AC-positive cells but not in ciliated cells. IL-13 treatment
      increased percentages of TMEM16A-positive cells, MUC5AC-positive cells, and cells
      coexpressing TMEM16A/MUC5AC, the expression of TMEM16A protein, and the secretion
      of MUC5AC. T16Ainh-A01, a TMEM16A inhibitor, attenuated these IL-13-induced
      effects. CONCLUSIONS: The expression of TMEM16A and MUC5AC are increased in
      CRSwNP, which might be a direct effect of Th2 cytokines present in the sinonasal
      mucosa in CRSwNP. Down-regulation of TMEM16A expression and MUC5AC secretion in
      HNPECs by T16Ainh-A01 indicates that TMEM16A might play an important role in
      mucin secretion in upper airway inflammatory diseases.

PMID- 25749772
TI  - IgE-Binding Epitope Mapping and Tissue Localization of the Major American
      Cockroach Allergen Per a 2.
AB  - PURPOSE: Cockroaches are the second leading allergen in Taiwan. Sensitization to
      Per a 2, the major American cockroach allergen, correlates with clinical severity
      among patients with airway allergy, but there is limited information on IgE
      epitopes and tissue localization of Per a 2. This study aimed to identify Per a 2
      linear IgE-binding epitopes and its distribution in the body of a cockroach.
      METHODS: The cDNA of Per a 2 was used as a template and combined with
      oligonucleotide primers specific to the target areas with appropriate restriction
      enzyme sites. Eleven overlapping fragments of Per a 2 covering the whole allergen
      molecule, except 20 residues of signal peptide, were generated by PCR. Mature Per
      a 2 and overlapping deletion mutants were affinity-purified and assayed for IgE
      reactivity by immunoblotting. Three synthetic peptides comprising the B cell
      epitopes were evaluated by direct binding ELISA. Rabbit anti-Per a 2 antibody was
      used for immunohistochemistry. RESULTS: Human linear IgE-binding epitopes of Per
      a 2 were located at the amino acid sequences 57-86, 200-211, and 299-309. There
      was positive IgE binding to 10 tested Per a 2-allergic sera in 3 synthetic
      peptides, but none in the controls. Immunostaining revealed that Per a 2 was
      localized partly in the mouth and midgut of the cockroach, with the most intense
      staining observed in the hindgut, suggesting that the Per a 2 allergen might be
      excreted through the feces. CONCLUSIONS: Information on the IgE-binding epitope
      of Per a 2 may be used for designing more specific diagnostic and therapeutic
      approaches to cockroach allergy.

PMID- 25749773
TI  - Profiles of IgE Sensitization to Der f 1, Der f 2, Der f 6, Der f 8, Der f 10,
      and Der f 20 in Korean House Dust Mite Allergy Patients.
AB  - PURPOSE: Measurement of IgE specific to purified house dust mite (HDM) allergens
      may improve allergy diagnosis. This study aimed to investigate the sensitization
      profiles of Korean HDM allergic subjects suffering from respiratory allergy and
      atopic dermatitis (AD) to Der f 1, Der f 2, Der f 6, Der f 8, Der f 10, and Der f
      20. METHODS: Recombinant HDM allergens were produced in Pichia pastoris (Der f 1)
      or Escherichia coli (5 allergens). IgE reactivity to the individual recombinant
      allergens and total extract of mite was assessed by ELISA. RESULTS: Der f 1 was
      recognized by 79.1%, Der f 2 by 79.1%, Der f 6 by 9.3%, Der f 8 by 6.2%, Der f 10
      by 6.2%, and Der f 20 by 6.6% of the patients' sera tested, while the prevalence
      of IgE reactivity to total mite extract was 94.7%. Combination of Der f 1 and Der
      f 2 had a sensitivity of 87.6%. Specific IgE to Der f 2 alone was detected from
      89.4% of HDM-sensitized respiratory allergy subjects and 92.3% to the combination
      of the 2 major allergens Der f 1 and Der f 2. However, sera from fewer patients
      with AD, namely 72.4% and 71.0%, recognized Der f 1 and Der f 2, respectively.
      The combination of 2 major allergens allowed diagnosis of 84.5% of the AD
      patients. No correlation between sensitization to specific allergens and HDM
      allergy entity was found. CONCLUSIONS: Der f 2 was the most frequently sensitized
      allergen among the HDM-sensitized respiratory and AD patients in Korea, and the
      combination of the group 1 and 2 major allergens increased the diagnostic
      sensitivity. Minor allergens did not significantly improve diagnostic
      sensitivity. However, further studies are needed to analyze the relationship
      between sensitization to other HDM allergens and the disease entity of the HDM
      allergy.

PMID- 25749774
TI  - IgE Reactivity of the Dog Lipocalin Allergen Can f 4 and the Development of a
      Sandwich ELISA for Its Quantification.
AB  - PURPOSE: Divergent results on the IgE reactivity of dog-allergic subjects to Can
      f 4 have been reported. The aim of this study was to evaluate the significance of
      Can f 4 in dog allergy and to develop an immunochemical method for measuring Can
      f 4 content in environmental samples. METHODS: We purified the natural dog
      allergen Can f 4 from a dog dander extract by monoclonal antibody-based affinity
      chromatography and generated its variant in a recombinant form. Sixty-three dog
      allergic patients and 12 nonallergic control subjects were recruited in the
      study. The IgE-binding capacity of natural Can f 4 and its recombinant variant
      was assessed by ELISA, immunoblotting, and skin prick tests (SPT). RESULTS:
      Eighty-one percent of the dog-allergic patients showed a positive result to the
      immunoaffinity-purified natural Can f 4 in IgE ELISA, but only 46% in IgE
      immunoblotting. Respective results with the recombinant Can f 4 variant were 54%
      and 49%. SPT results reflected those obtained in ELISA and immunoblotting. The
      overall IgE reactivity of the immunoaffinity-purified natural Can f 4 was found
      to depend strongly on the integrity of the allergen's conformation. A sandwich
      ELISA based on monoclonal antibodies was found to be functional for measuring Can
      f 4 in environmental samples. CONCLUSIONS: Can f 4 is a major allergen of dog
      together with Can f 1 and Can f 5. In combination with other dog allergens, it
      improves the reliability of allergy tests in dog allergy.

PMID- 25749775
TI  - Der p2 Internalization by Epithelium Synergistically Augments Toll-like Receptor
      Mediated Proinflammatory Signaling.
AB  - PURPOSE: House-dust-mite (HDM) major allergen Der p2 shares homology and function
      with Toll-like receptor (TLR) signaling protein myeloid differentiation-2 (MD2)
      and may lead to airway inflammation. Should Der p2 be internalized by human
      airway epithelium, it has the theoretical propensity to potentiate epithelium
      activation. This study aimed to demonstrate the internalization of Der p2 by
      airway epithelium and to investigate the effects of Der p2 on MD2 expression and
      epithelium activation. METHODS: Internalization of recombinant, enhanced green
      fluorescent protein-labelled Der p2 (rDer p2-EGFP) into human airway epithelium
      (BEAS-2B) was tracked by laser confocal microscopy and confirmed by
      immunoblotting. Reverse-transcription polymerase chain reaction (RT-PCR),
      immunoblotting, and immunohistochemical staining were used to determine the
      effect of Der p2 on MD2 expression in vitro and ex vivo. Expression of messenger
      RNA (mRNA) encoding receptors/cytokines was measured by RT-PCR. Secretion of
      interleukin-6/interleukin-8 (IL-6/IL-8) was measured by enzyme-linked
      immunosorbent assay (ELISA). RESULTS: Internalization of Der p2 by BEAS-2B was
      confirmed by confocal microscopy and immunoblotting using rDer p2-EGFP and rDer
      p2, respectively. Expression of MD2 protein was increased in BEAS-2B and human
      nasal polyp airway epithelium cultured with rDer p2. Recombinant Der p2-cultured
      BEAS-2B caused little spontaneous IL-6/IL-8 secretion but significantly augmented
      by TLR ligand LPS. IL-6 secretion was up-regulated after MD2 transfection.
      Internalization of Der p2 was reduced by TLR2 RNA knockdown. Dexamethasone,
      calcitriol, anti-MD2/anti-TLR2 antibodies, and signalling inhibitors
      significantly reduced LPS+Der p2-induced IL-6/IL-8 secretion. CONCLUSIONS: Human
      airway epithelium may internalize Der p2, which potentiates the response to
      environmental proinflammatory stimuli through MD2 and TLRs. This study highlights
      a novel mechanism and alleviates IL-6/IL-8 secretion in mite-induced airway
      inflammation.

PMID- 25749776
TI  - The Association of Lung Function, Bronchial Hyperresponsiveness, and Exhaled
      Nitric Oxide Differs Between Atopic and Non-atopic Asthma in Children.
AB  - PURPOSE: Although many previous studies have attempted to identify differences
      between atopic asthma (AA) and non-atopic asthma (NAA), they have mainly focused
      on the difference of each variable of lung function and airway inflammation. The
      aim of this study was to evaluate relationships between lung function, bronchial
      hyperresponsiveness (BHR), and the exhaled nitric oxide (eNO) levels in children
      with AA and NAA. METHODS: One hundred and thirty six asthmatic children aged 5-15
      years and 40 normal controls were recruited. Asthma cases were classified as AA
      (n=100) or NAA (n=36) from skin prick test results. Lung function, BHR to
      methacholine and adenosine-5'-monophosphate (AMP), eNO, blood eosinophils, and
      serum total IgE were measured. RESULTS: The AA and NAA cases shared common
      features including a reduced small airway function and increased BHR to
      methacholine. However, children with AA showed higher BHR to AMP and eNO levels
      than those with NAA. When the relationships among these variables in the AA and
      NAA cases were evaluated, the AA group showed significant relationships between
      lung function, BHR to AMP or methacholine and eNO levels. However, the children
      in the NAA group showed an association between small airway function and BHR to
      methacholine only. CONCLUSIONS: These findings suggest that the pathogenesis of
      NAA may differ from that of AA during childhood in terms of the relationship
      between lung function, airway inflammation and BHR.

PMID- 25749777
TI  - Expression and Regulation of Transcription Factor FoxA2 in Chronic Rhinosinusitis
      With and Without Nasal Polyps.
AB  - PURPOSE: Chronic rhinosinusitis (CRS) is characterized by the excessive
      production of mucus. However, the molecular mechanism underlying mucin
      overproduction in CRS with or without nasal polyps (CRSwNP and CRSsNP,
      respectively) is poorly understood. This study was conducted to assess the
      importance of the transcription factor FoxA2 in mucin production and to
      investigate the targeting of FoxA2 as a potential therapeutic strategy for mucus
      hypersecretion in CRS patients. METHODS: We enrolled 15 CRSwNP patients, 15
      CRSsNP patients, and 10 normal controls in this study. The expression levels of
      FoxA2, MUC5AC, and MUC5B in inflamed and healthy nasal tissues were examined via
      immunohistochemistry and quantitative reverse transcription-polymerase chain
      reaction, and the levels of several proinflammatory cytokines in nasal secretions
      were measured via FlowCytomix analysis. In addition, the expression of MUC5AC and
      FoxA2 was determined in polyp-derived epithelial cells and NCI-H292 cells after
      in vitro stimulation. RESULTS: FoxA2 was significantly down-regulated, and MUC5AC
      and MUC5B were significantly up-regulated in both the CRSwNP and CRSsNP patients
      compared to the controls (P<0.05), and the protein level of FoxA2 was negatively
      associated with the IL-6 level in the CRS patients (P<0.05). IL-6 significantly
      increased MUC5AC expression but inhibited FoxA2 expression in vitro (P<0.05).
      Transfection with a FoxA2 expression plasmid significantly decreased MUC5AC
      promoter activity (P<0.05) and inhibited IL-6-induced MUC5AC production (P<0.05).
      In addition, clarithromycin significantly alleviated IL-6-induced FoxA2
      suppression and decreased MUC5AC expression in vitro (P<0.05). CONCLUSIONS: Our
      findings suggest that FoxA2 may be considered a therapeutic target for the
      modulation of mucus hypersecretion in CRS patients.

PMID- 25749778
TI  - Antiallergic Function of KR62980, a Peroxisome Proliferator-Activated Receptor
      gamma Agonist, in a Mouse Allergic Rhinitis Model.
AB  - PURPOSE: Peroxisome proliferator-activated receptor gamma (PPAR-gamma) has been
      shown to play an important role in the control of inflammatory responses acting
      on macrophages, mast cells, T cells and eosinophils. A novel PPAR-gamma ligand,
      KR62980 have been recently focused on due to the lower undesirable effects than
      other PPAR-gamma ligands such as rosiglitazone and pioglitazone. The present
      study was aimed to investigate the effects of KR62980 on nasal symptoms and
      immunopathological profiles in allergic nasal mucosa in murine allergic rhinitis
      model. METHODS: BALB/c mice were sensitized and challenged intranasally with
      ovalbumin (OVA). KR62980 was administered intraperitoneally or orally 3 hours
      before each intranasal OVA challenge. RESULTS: Administration of KR62980
      significantly decreased the number of nasal rubbing, nasal sneezing, ova-specific
      IgE and total IgE in serum, secretion of Interleukin (IL)-4, IL-5, and IL-17 from
      the spleen and eosinophilic infiltration in the nasal mucosa. KR62980 decreased
      the expression of IL-4, IL-5 and IL-10 mRNAs in the nasal mucosal tissue, while,
      it elevated the level of IL-10 and IFN-gamma in splenocyte culture. KR62980
      seemed to decrease IL-17 level in local and systemic level even though it did not
      reach to statistical significance. The anti-inflammatory effect was more definite
      when the KR62980 was administered intraorally than intraperitoneally.
      CONCLUSIONS: A novel PPAR-gamma ligand, KR62980 can attenuate OVA-induced
      allergic inflammation in mice mainly through modulation of Th2 cytokines. This
      finding suggests that PPAR-gamma might have a role in the treatment of allergic
      rhinitis.

PMID- 25749779
TI  - Inhibitory Effect of Delphinidin on Extracellular Matrix Production via the
      MAPK/NF-kappaB Pathway in Nasal Polyp-Derived Fibroblasts.
AB  - PURPOSE: Nasal polyps are associated with chronic inflammation of the mucous
      membranes in the nose and paranasal sinuses and involved in extracellular matrix
      (ECM) accumulation. Delphinidin promotes ECM degradation in hepatitis and cardiac
      fibrosis. The aims of this study were to examine the inhibitory effect of
      delphinidin on TGF-beta1-induced myofibroblast differentiation and ECM
      accumulation, and to determine the underlying mechanisms in nasal polyp-derived
      fibroblasts (NPDFs). METHODS: NPDFs were stimulated with TGF-beta1, with or
      without delphinidin, and the expression levels of alpha-SMA, fibronectin, and
      collagen type I were determined by RT-PCR, Western blot analysis, and collagen
      assay. The expression of alpha-SMA protein was measured by immunocytochemical
      staining. Mitogen-activated protein kinase and NF-kappaB activation induced by
      TGF-beta1 were determined by Western blot analysis. The transcriptional activity
      of NF-kappaB was measured by luciferase assay. RESULTS: The expression levels of
      alpha-SMA, fibronectin, and collagen type I increased in TGF-beta1-stimulated
      NPDFs. In TGF-beta1-induced NPDFs, delphinidin inhibited the expression of alpha
      SMA, fibronectin, and collagen. Inhibitors of MAPK and NF-kappaB blocked the
      expression of alpha-SMA, fibronectin, and collagen type I. Delphinidin suppressed
      the activation of MAPK and NF-kappaB induced by TGF-beta1 stimulation.
      CONCLUSIONS: These results suggest that delphinidin may inhibit TGF-beta1-induced
      myofibroblast differentiation and ECM production through the MAPK/NF-kappaB
      signaling pathway in NPDFs.

PMID- 25749780
TI  - Association of Single Nucleotide Polymorphisms in the MD-2 Gene Promoter Region
      With Der p 2 Allergy.
AB  - PURPOSE: Sensitization to house dust mite (Dermatophagoides pteronyssinus) is a
      considerable risk factor for the progression of allergic disease. The group 2
      allergen from Dermatophagoides pteronyssinus, Der p 2, is considered a major one
      in patients with specific immunoglobulin E (IgE) to Der p 2. Der p 2 has
      structural homology with myeloid differentiation 2 (MD-2), which is involved in
      the lipopolysaccharide-binding component of the Toll-like receptor 4 signaling
      pathway and the development of inflammation. The aim of this study was to examine
      the genetic association of single nucleotide polymorphisms (SNPs) in the promoter
      region of MD-2 with Der p 2-sensitive allergy. METHODS: We investigated
      associations between cohort's characteristics, including 280 allergic and 80
      healthy subjects by examining total IgE, eosinophils, D. pteronyssinus-specific
      IgE, Der p 2-specific IgE, the number of IgE-producing B cells induced by Der p
      2, and the odds ratio of allergic symptoms. RESULTS: Based on the 1,000 genome
      project data, the minor allele frequencies of the rs1809441 and rs1809442 are
      0.467 and 0.474, respectively. However, the correlation of linkage disequilibrium
      (LD) between these 2 SNPs is D'=1, the genotype frequencies of the 2 MD-2 (LY96)
      SNPs (rs1809441 and rs1809442) that are located nearby were significantly
      different between allergic and health subjects: the TT genotype of rs1809441 and
      the GG genotype of rs1809442 were more frequent in allergic subjects than in
      healthy subjects (16.1% vs 2.5% in both genotypes). The allergic patients with
      these genotypes exhibited significantly higher levels of D. pteronyssinus
      specific IgE and Der p 2-specific Ig E, and a larger number of Der p 2-activated
      B cells. In addition, these 2 SNPs in the MD-2 promoter region were significantly
      associated with the prevalence of nasal, skin, and asthmatic allergic symptoms.
      CONCLUSIONS: Our results indicated that 2 SNPs in the MD-2 promoter region were
      significantly associated with Der p 2-specific Ig E, and thereby suggest that
      these SNPs may play a major role in susceptibility to Der p 2-triggered immune
      responses in a Taiwanese population.

PMID- 25749781
TI  - Diagnostic Decision Points of Specific IgE Concentrations in Korean Children With
      Egg and Cow's Milk Allergies.
AB  - PURPOSE: The purpose of this study was to evaluate the utility of specific IgE
      (sIgE) concentrations for the diagnosis of immediate-type egg and cow's milk (CM)
      allergies in Korean children and to determine the optimal cutoff levels. METHODS:
      In this prospective study, children >=12 months of age with suspected egg or CM
      allergy were enrolled. Food allergy was diagnosed by an open oral food challenge
      (OFC) or through the presence of a convincing history after ingestion of egg or
      CM. The cutoff levels of sIgE for egg white (EW) and CM were determined by
      analyzing the receiver operating characteristic curves. RESULTS: Out of 273
      children, 52 (19.0%) were confirmed to have egg allergy. CM allergy was found in
      52 (23.1%) of 225 children. The EW-sIgE concentration indicating a positive
      predictive value (PPV) of >90% was 28.1 kU/L in children <24 months of age and
      22.9 kU/L in those >=24 months of age. For CM-sIgE, the concentration of 31.4
      kU/L in children <24 months of age and 10.1 kU/L in those >=24 months of age
      indicated a >90% PPV. EW-sIgE levels of 3.45 kU/L presented a negative predictive
      value (NPV) of 93.6% in children <24 months of age, while 1.80 kU/L in those >=24
      months of age presented a NPV of 99.2%. The CM-sIgE levels of 0.59 kU/L in
      children <24 months of age and 0.94 kU/L in those >=24 months of age showed NPVs
      of 100% and 96.9%. CONCLUSIONS: Our results indicate that different diagnostic
      decision points (DDPs) of sIgE levels should be used for the diagnosis of egg or
      CM allergy in Korean children. The data also suggest that DDPs with high PPV and
      high NPV are useful for determining whether OFC is required in children with
      suspected egg or CM allergy.

PMID- 25749782
TI  - Japanese Cedar (Cryptomeria japonica) Pollinosis in Jeju, Korea: Is It
      Increasing?
AB  - Jeju is an island in South Korea located in a temperate climate zone. The
      Japanese cedar tree (JC) has become the dominant tree species while used widely
      to provide a windbreak for the tangerine orchard industry. An increase in pollen
      counts precedes atopic sensitization to pollen and pollinosis, but JC pollinosis
      in Jeju has never been studied. We investigated JC pollen counts, sensitization
      to JC pollen, and JC pollinosis. Participants were recruited among schoolchildren
      residing in Jeju City, the northern region (NR) and Seogwipo City, the southern
      region (SR) of the island. The JC pollen counts were monitored. Sensitization
      rates to common aeroallergens were evaluated by skin prick tests. Symptoms of
      pollinosis were surveyed. Among 1,225 schoolchildren (49.6% boys, median age 13
      years), 566 (46.2%) were atopic. The rate of sensitization to Dermatophagoides
      pteronyssinus (35.8%) was highest, followed by D. farinae (26.2%), and JC pollen
      (17.6%). In the SR, 156 children (23.8%) were sensitized to JC pollen; this rate
      was significantly higher than that in the NR (59 children, 10.4%, P<0.001). A
      significant increment in the sensitization rate for JC pollen with increasing
      school level was observed only in the SR. JC pollen season in the SR started
      earlier and lasted longer than that in the NR. JC pollen season in Jeju was
      defined as extending from late January to mid-April. The prevalence of JC
      pollinosis was estimated to be 8.5%. The prevalence differed significantly
      between the NR and SR (5.3% vs 11.3%, P<0.001), mainly due to the difference in
      sensitization rates. JC pollen is the major outdoor allergen for early spring
      pollinosis in Jeju. JC pollen season is from late January to mid-April. Warmer
      weather during the flowering season scatters more JC pollen in the atmosphere,
      resulting in a higher sensitization rate in atopic individuals and, consequently,
      making JC pollinosis more prevalent. 

PMID- 25749783
TI  - Fractional exhaled nitric oxide: comparison between portable devices and
      correlation with sputum eosinophils.
AB  - This study was performed to compare the 2 different portable devices measuring
      fractional exhaled nitric oxide (FeNO) and to see the correlation between FeNO
      and induced sputum eosinophil count (ISE). Forty consecutive subjects clinically
      suspected to have asthma underwent FeNO measurement by NIOX-MINO(r) and
      NObreath(r) concurrently. All also had induced sputum analysis, methacholine
      provocation test or bronchodilator response test, and spin prick test. Agreement
      between the 2 devices was evaluated. The correlation between FeNO and ISE was
      assessed, as well as the cut-off level of FeNO to identify ISE >=3%. The
      intraclass correlation coefficient (ICC) between FeNO levels measured by NIOX
      MINO(r) (FeNO(NIOX-MINO)) and NObreath(r) (FeNO(NObreath)) was 0.972 with 95%
      confidence interval of 0.948-0.985. The 95% limits of agreement were -28.9 to
      19.9 ppb. The correlation coefficient between ISE and FeNO(NIOX-MINO) was 0.733
      (P<0.001), and 0.751 between ISE and FeNO(NObreath) (P<0.001). The ROC curve
      found that the FeNO(NIOXMINO) of 37.5 ppb and the FeNO(NObreath) of 36.5 ppb
      identified ISE >=3% with 90% sensitivity and 81% specificity. Age, sex, body mass
      index, smoking history, atopy, and the presence of asthma did not affect the FeNO
      level and its correlation with ISE. The NIOX-MINO (r) and NObreath(r) agree with
      each other to a high degree. Both devices showed close correlation with ISE with
      similar cut-off value in identifying ISE >=3%. 

PMID- 25749784
TI  - Immunomodulatory Effects of Lactobacillus salivarius LS01 and Bifidobacterium
      breve BR03, Alone and in Combination, on Peripheral Blood Mononuclear Cells of
      Allergic Asthmatics.
AB  - The aim of this study was to evaluate probiotic characteristics of Lactobacillus
      salivarius LS01 and Bifidobacterium breve BR03 alone and in combination and their
      immunomodulatory activity in asthmatic subjects. Subjects affected by allergic
      asthma were recruited. Initially, LS01 and BR03 were analyzed for their growth
      compatibility by a broth compatibility assay. To study the antimicrobial activity
      of probiotic strains, an agar diffusion assay was performed. Finally, cytokine
      production by peripheral blood mononuclear cells (PBMCs) stimulated with LS01 and
      BR03 was determined by means of specific quantitative enzyme-linked immunosorbent
      assay (ELISA). The growth of some clinical pathogens were slightly inhibited by
      LS01 and LS01-BR03 co-culture supernatant not neutralized to pH 6.5, while only
      the growth of E. coli and S. aureus was inhibited by the supernatant of LS01 and
      LS01-BR03 neutralized to pH 6.5. Furthermore, LS01 and BR03 combination was able
      to decrease the secretion of proinflammatory cytokines by PBMCs, leading to an
      intense increase in IL-10 production. L. salivarius LS01 and B. breve BR03 showed
      promising probiotic properties and beneficial immunomodulatory activity that are
      increased when the 2 strains are used in combination in the same formulation. 

PMID- 25749785
TI  - Sorafenib induces delayed-onset cutaneous hypersensitivity: a case series.
AB  - Sorafenib is an oral multikinase inhibitor with clinical activity against
      hepatocellular carcinoma (HCC) and renal cell carcinoma. Administration of
      sorafenib carries a variety of adverse cutaneous reactions. Common adverse
      effects induced by sorafenib include hand-foot skin reactions, facial erythema,
      splinter subungual hemorrhage, and alopecia. Although erythema multiforme (EM)
      related to sorafenib has been reported, delayed-type cutaneous hypersensitivity
      reactions are rare in patients treated with sorafenib and there has been no case
      of Stevens-Johnson syndrome (SJS) reported so far. We recently experienced 3
      cases of delayed-type cutaneous hypersensitivity related to administration of
      sorafenib. The first case was a 47-year female had targetoid erythematous rashes
      on her arms 12 days after starting sorafenib for HCC. The rashes spread from the
      arms to the trunk rapidly except for the hands and feet, and erosive lesions
      developed in the oral mucosa and lips. She was diagnosed as SJS. The second case
      was an 81-year-old male had maculopapular eruptions with multiple targetoid
      lesions on the trunk, arms, and legs 10 days after starting sorafenib for his
      HCC. There was no evidence of mucosal involvement. He was diagnosed with EM. The
      last one was a 20-year-old female developed generalized maculopapular eruptions
      in the whole body 10 days after starting sorafenib for the treatment of HCC. All
      3 patients completely recovered after discontinuation of sorafenib. 

PMID- 25749786
TI  - Multivariate modelling of prostate cancer combining magnetic resonance derived
      T2, diffusion, dynamic contrast-enhanced and spectroscopic parameters.
AB  - OBJECTIVES: The objectives are determine the optimal combination of MR parameters
      for discriminating tumour within the prostate using linear discriminant analysis
      (LDA) and to compare model accuracy with that of an experienced radiologist.
      METHODS: Multiparameter MRIs in 24 patients before prostatectomy were acquired.
      Tumour outlines from whole-mount histology, T2-defined peripheral zone (PZ), and
      central gland (CG) were superimposed onto slice-matched parametric maps. T2,
      Apparent Diffusion Coefficient, initial area under the gadolinium curve, vascular
      parameters (K(trans),Kep,Ve), and (choline+polyamines+creatine)/citrate were
      compared between tumour and non-tumour tissues. Receiver operating characteristic
      (ROC) curves determined sensitivity and specificity at spectroscopic voxel
      resolution and per lesion, and LDA determined the optimal multiparametric model
      for identifying tumours. Accuracy was compared with an expert observer. RESULTS:
      Tumours were significantly different from PZ and CG for all parameters (all p <
      0.001). Area under the ROC curve for discriminating tumour from non-tumour was
      significantly greater (p < 0.001) for the multiparametric model than for
      individual parameters; at 90 % specificity, sensitivity was 41 % (MRSI voxel
      resolution) and 59 % per lesion. At this specificity, an expert observer achieved
      28 % and 49 % sensitivity, respectively. CONCLUSION: The model was more accurate
      when parameters from all techniques were included and performed better than an
      expert observer evaluating these data. KEY POINTS: * The combined model increases
      diagnostic accuracy in prostate cancer compared with individual parameters * The
      optimal combined model includes parameters from diffusion, spectroscopy,
      perfusion, and anatominal MRI * The computed model improves tumour detection
      compared to an expert viewing parametric maps.

PMID- 25749787
TI  - Investigation of Apparent Diffusion Coefficient from Ultra-high b-Values in
      Parkinson's Disease.
AB  - OBJECTIVES: To assess brain damage in Parkinson's disease (PD) based on apparent
      diffusion coefficient (ADC) data obtained from ultra-high b-values. METHODS:
      Eighteen PD patients and 18 controls received diffusion-weighted imaging (DWI)
      with standard b-values (0, 1,000 s/mm(2)) and 15 b-values (0-5,000 s/mm(2)).
      Standard ADC (ADCst) maps were calculated from standard b-values, while maps of
      pure diffusion coefficients (D), pseudo-diffusion coefficients (D(*)), and ultra
      high ADCs (ADCuh) were calculated from the 15 b-values using a tri-component
      model. In this model, D and D(*) values were quantified with a bi-exponential
      equation using b-values less than 2,000 s/mm(2), while ADCuh was quantified by
      fitting the signals at ultra-high b-values (2,000-5,000 s/mm(2)) to the mono
      exponential equation. ADCst, ADCuh, D, and D(*) of the globus pallidus (GP),
      putamen (P), and substantia nigra (SN) were compared between PD patients and
      normal control subjects. RESULTS: ADCuh of the GP, P, and SN was significantly
      lower in PD patients than those in control subjects (P < 0.001), while ADCst, D,
      and D(*) of the GP, P and SN were not different between the two groups (P >
      0.05). CONCLUSIONS: ADCuh may be a useful measurement for evaluating brain damage
      in PD patients. KEY POINTS: * DWI with ultra-high b-values may provide new
      insight into Parkinson's disease pathology * ADC calculated using ultra-high b
      values is different between PD and controls * ADC uh may be associated with water
      transportation by aquaporins.

PMID- 25749788
TI  - Chemistry of withaferin-A: chemo, regio, and stereoselective synthesis of novel
      spiro-pyrrolizidino-oxindole adducts of withaferin-A via one-pot three-component
      [3+2] azomethine ylide cycloaddition and their cytotoxicity evaluation.
AB  - Withaferin-A (WA) has attracted the attention of chemists as well as biologists
      due to its interesting structure and various bio-activities. In light of the
      promising biological importance of WA as well as pyrrolidine-2-spiro-3'-oxindole
      ring system, we became interested in the synthesis of a combined motif involving
      both the ring systems via the 1,3-dipolar cycloaddition of WA at Delta(2)-bond of
      the alpha,beta-unsaturated carbonyl system. We now report a facile, atom-economic
      synthesis of novel spiro-pyrrolizidino-oxindole adducts of withaferin-A (10
      compounds) via the intermolecular cycloaddition of azomethine ylides generated in
      situ from proline and isatins/acenaphthoquinone. The reaction is highly chemo,
      regio, and stereoselective affording the cis-fused products with beta-orienting
      hydrogen. The structures were determined by 1D/2D NMR spectroscopic data analysis
      and unequivocally confirmed by X-ray crystallographic analysis in some cases.
      Bioevaluation of the compounds against six cancer lines (e.g., CHO, HepG2, HeLa,
      HEK 293, MDCK-II, and Caco-2) identified 4 promising potential anticancer
      compounds.

PMID- 25749790
TI  - ABC Spotlight on effect-directed analysis--dose instead of concentration.

PMID- 25749789
TI  - MicroRNAs as potential biomarkers for noninvasive detection of fetal trisomy 21.
AB  - PURPOSE: The objective of this study was to discover a panel of microRNAs
      (miRNAs) as potential biomarkers for noninvasive prenatal testing (NIPT) of
      trisomy 21 (T21) and to predict the biological functions of identified biomarkers
      using bioinformatics tools. METHODS: Using microarray-based genome-wide
      expression profiling, we compared the expression levels of miRNAs in whole blood
      samples from non-pregnant women, whole blood samples from pregnant women with
      euploid or T21 fetuses, and placenta samples from euploid or T21 fetuses. We
      analyzed the differentially expressed miRNAs according to disease and tissue type
      (P value <0.05 and two-fold expression change). To predict functions of target
      genes of miRNAs, the functional annotation tools were used. RESULTS: We
      identified 299 miRNAs which reasonably separate the whole blood from the
      placenta. Among the identified miRNAs, 150 miRNAs were up-regulated in the
      placenta, and 149 miRNAs were down-regulated. Most of the up-regulated miRNAs in
      the placenta were members of the mir-498, mir-379, and mir-127 clusters. Among
      the up-regulated miRNAs in the placenta, mir-1973 and mir-3196 were expressed at
      higher levels in the T21 placenta than in the euploid placenta. The two miRNAs
      potentially regulate 203 target genes that are involved in development of brain,
      central nervous system, and nervous system. The genes are significantly
      associated with T21-related disorder such as congenital abnormalities, mental
      disorders, and nervous system diseases. CONCLUSIONS: Our study indicates placenta
      specific miRNAs that may be potential biomarkers for NIPT of fetal T21 and
      provides new insights into the molecular mechanisms of T21 via regulation of
      miRNAs.

PMID- 25749791
TI  - Analysis of doxorubicin distribution in MCF-7 cells treated with drug-loaded
      nanoparticles by combination of two fluorescence-based techniques, confocal
      spectral imaging and capillary electrophoresis.
AB  - The intracellular distribution of the antiancer drug doxorubicin (DOX) was
      followed qualitatively by fluorescence confocal spectral imaging (FCSI) and
      quantitatively by capillary electrophoresis (CE). FCSI permits the localization
      of the major fluorescent species in cell compartments, with spectral shifts
      indicating the polarity of the respective environment. However, distinction
      between drug and metabolites by FCSI is difficult due to their similar
      fluorochromes, and direct quantification of their fluorescence is complicated by
      quantum yield variation between different subcellular environments. On the other
      hand, capillary electrophoresis with fluorescence detection (CE-LIF) is a
      quantitative method capable of separating doxorubicin and its metabolites. In
      this paper, we propose a method for determining drug and metabolite concentration
      in enriched nuclear and cytosolic fractions of cancer cells by CE-LIF, and we
      compare these data with those of FCSI. Significant differences in the subcellular
      distribution of DOX are observed between the drug administered as a molecular
      solution or as a suspension of drug-loaded iron oxide nanoparticles coated with
      polyethylene glycol. Comparative analysis of the CE-LIF vs FCSI data may lead to
      a tentative calibration of this latter method in terms of DOX fluorescence
      quantum yields in the nucleus and more or less polar regions of the cytosol. 

PMID- 25749792
TI  - A simple method for the subnanomolar quantitation of seven ophthalmic drugs in
      the rabbit eye.
AB  - This study describes the development and validation of a new liquid
      chromatography-tandem mass spectrometry (MS/MS) method capable of simultaneous
      quantitation of seven ophthalmic drugs-pilocarpine, lidocaine, atropine,
      proparacaine, timolol, prednisolone, and triamcinolone acetonide-within regions
      of the rabbit eye. The complete validation of the method was performed using an
      Agilent 1100 series high-performance liquid chromatography system coupled to a
      4000 QTRAP MS/MS detector in positive TurboIonSpray mode with pooled drug
      solutions. The method sensitivity, evaluated by the lower limit of quantitation
      in two simulated matrices, yielded lower limits of quantitation of 0.25 nmol L(
      1) for most of the drugs. The precision in the low, medium, and high ranges of
      the calibration curves, the freeze-thaw stability over 1 month, the intraday
      precision, and the interday precision were all within a 15% limit. The method was
      used to quantitate the different drugs in the cornea, aqueous humor, vitreous
      humor, and remaining eye tissues of the rabbit eye. It was validated to a
      concentration of up to 1.36 ng/g in humors and 5.43 ng/g in tissues. The
      unprecedented low detection limit of the present method and its ease of
      implementation allow easy, robust, and reliable quantitation of multiple drugs
      for rapid in vitro and in vivo evaluation of the local pharmacokinetics of these
      compounds.

PMID- 25749793
TI  - An LCMS method for the assay of melittin in cosmetic formulations containing bee
      venom.
AB  - There is a growing interest in the potential of bee venom in cosmetics as a
      rejuvenating agent. Products currently on the market do not specify exactly their
      content of bee venom (BV). Therefore, we developed a method for the detection and
      quantification of melittin, as a marker of bee venom content, in selected
      commercial creams which contained BV according to their marketing claims, in
      order to gauge the relative quality of such formulations. A quantitative method
      was achieved following a rigorous extraction procedure involving sonication,
      liquid-liquid extraction and solid phase extraction since carryover of excipients
      was found to cause a rapid deterioration in the chromatographic performance. The
      method employed a standard additions approach using, as spiking standard,
      purified melittin isolated from bee venom and standardised by quantitative NMR.
      The aqueous extracts of the spiked creams were analysed by reversed phase LCMS on
      an LTQ Orbitrap mass spectrometer. The purity of the melittin spiking standard
      was determined to be 96.0%. The lowest measured mean melittin content in the
      creams was 3.19 ppm (+/-1.58 ppm 95% CI) while the highest was 37.21 ppm (+/-2.01
      ppm 95% CI). The method showed adequate linearity (R (2) >= 0.98) and a recovery
      of 87.7-102.2% from a spiked blank cream. An assay precision of <20% RSD was
      achieved for all but one sample where the RSD value was 27.5%. The method was
      sensitive enough for use in routine assay of BV-containing cosmetic creams.
      Differences in the melittin content of the commercial products assayed were
      nearly tenfold.

PMID- 25749794
TI  - Fast determination of harmala alkaloids in edible algae by capillary
      electrophoresis mass spectrometry.
AB  - The use of algae as a foodstuff is rapidly expanding worldwide from the East
      Asian countries, where they are also used for medical care. Harmala alkaloids
      (HAlk) are a family of bioactive compounds found in the extracts of some plants,
      including wakame (Undaria pinnatifida), an edible marine invasive algae. HAlks
      are based on a characteristic beta-carboline structure with at least one amino
      ionizable group. In this work, we report the successful separation of a mixture
      of six HAlks (harmine, harmaline, harmol, harmalol, harmane, and norharmane) by
      capillary electrophoresis ion-trap mass spectrometry (CE-IT-MS) in less than 8
      min. Optimum separation in fused-silica capillaries and detection sensitivity in
      positive-ion mode were achieved using a background electrolyte (BGE) with 25 mmol
      L(-1) ammonium acetate (pH 7.8) and 10% (v/v) methanol, and a sheath liquid with
      60:40 (v/v) isopropanol-water and 0.05% (v/v) formic acid. The separation method
      was validated in terms of linearity, limits of detection and quantification,
      repeatability, and reproducibility. Later, a sample pretreatment was carefully
      optimized to determine HAlks in commercial wakame samples with excellent recovery
      and repeatability. For the complex wakame extracts, the MS-MS fragmentation
      patterns of the different HAlks were useful to ensure a reliable identification.
      The complete procedure was validated using the standard-addition calibration
      method, determining matrix effects on the studied compounds. Harmalol, harmine,
      and harmaline were naturally present in the samples and were quantified at very
      low concentrations, ranging from 7 to 24 MUg kg(-1) dry algae.

PMID- 25749795
TI  - A preliminary study on postmortem interval estimation of suffocated rats by GC
      MS/MS-based plasma metabolic profiling.
AB  - Estimation of postmortem interval (PMI) is an important goal in judicial autopsy.
      Although many approaches can estimate PMI through physical findings and
      biochemical tests, accurate PMI calculation by these conventional methods remains
      difficult because PMI is readily affected by surrounding conditions, such as
      ambient temperature and humidity. In this study, Sprague-Dawley (SD) rats (10
      weeks) were sacrificed by suffocation, and blood was collected by dissection at
      various time intervals (0, 3, 6, 12, 24, and 48 h; n = 6) after death. A total of
      70 endogenous metabolites were detected in plasma by gas chromatography-tandem
      mass spectrometry (GC-MS/MS). Each time group was separated from each other on
      the principal component analysis (PCA) score plot, suggesting that the various
      endogenous metabolites changed with time after death. To prepare a prediction
      model of a PMI, a partial least squares (or projection to latent structure, PLS)
      regression model was constructed using the levels of significantly different
      metabolites determined by variable importance in the projection (VIP) score and
      the Kruskal-Wallis test (P < 0.05). Because the constructed PLS regression model
      could successfully predict each PMI, this model was validated with another
      validation set (n = 3). In conclusion, plasma metabolic profiling demonstrated
      its ability to successfully estimate PMI under a certain condition. This result
      can be considered to be the first step for using the metabolomics method in
      future forensic casework. 

PMID- 25749796
TI  - Rapid evaluation of 25 key sphingolipids and phosphosphingolipids in human plasma
      by LC-MS/MS.
AB  - We report on a new, sensitive, and fast LC-MS/MS method for the simultaneous
      determination of 25 key sphingolipid components in human plasma, including
      phosphorylated sphinganine and sphingosine, in a single 9-min run. This method
      enables an effective and high-throughput coverage of the metabolic changes
      involving the sphingolipidome during physiological or pathological states. The
      method is based on liquid-liquid extraction followed by reversed-phase LC-MS/MS.
      Exogenous odd-chain lipids are used as cost-effective but reliable internal
      standards. The method was fully validated in surrogate matrix and naive human
      plasma following FDA guidelines. Sample stability and dilution integrity were
      also tested and verified. 

PMID- 25749797
TI  - Quantitation of endogenous nucleoside triphosphates and nucleosides in human
      cells by liquid chromatography tandem mass spectrometry.
AB  - Nucleosides and nucleoside triphosphates are the building blocks of nucleic acids
      and important bioactive metabolites, existing in all living cells. In the present
      study, two liquid chromatography tandem mass spectrometry methods were developed
      to quantify both groups of compounds from the same sample with a shared
      extraction procedure. After a simple protein precipitation with methanol, the
      nucleosides were separated with reversed phase chromatography on an Atlantis T3
      column while for the separation of the nucleoside triphosphates, an anion
      exchange column (BioBasic AX) was used. No addition of ion pair reagent was
      required. A 5500 QTrap was used as analyzer, operating as triple quadrupole. The
      analytical method for the nucleoside triphosphates has been validated according
      to the guidelines of the US Food and Drug Administration. The lower limit of
      quantification values were determined as 10 pg on column (0.5 ng/mL in the
      injection solution) for deoxyadenosine triphosphate and deoxyguanosine
      triphosphate, 20 pg (1 ng/mL) for deoxycytidine triphosphate and thymidine
      triphosphate, 100 pg (5 ng/mL) for cytidine triphosphate and guanosine
      triphosphate, and 500 pg (25 ng/mL) for adenosine triphosphate und uridine
      triphosphate respectively. This methodology has been applied to the quantitation
      of nucleosides and nucleoside triphosphates in primary human CD4 T lymphocytes
      and macrophages. As expected, the concentrations for ribonucleosides and
      ribonucleoside triphophates were considerably higher than those obtained for the
      deoxy derivatives. Upon T cell receptor activation, the levels of all analytes,
      with the notable exceptions of deoxyadenosine triphosphate and deoxyguanosine
      triphosphate, were found to be elevated in CD4 T cells. 

PMID- 25749798
TI  - Quantitative analysis of PEG-functionalized colloidal gold nanoparticles using
      charged aerosol detection.
AB  - Surface characteristics of a nanoparticle, such as functionalization with
      polyethylene glycol (PEG), are critical to understand and achieve optimal
      biocompatibility. Routine physicochemical characterization such as UV-vis
      spectroscopy (for gold nanoparticles), dynamic light scattering, and zeta
      potential are commonly used to assess the presence of PEG. However, these
      techniques are merely qualitative and are not sensitive enough to distinguish
      differences in PEG quantity, density, or presentation. As an alternative, two
      methods are described here which allow for quantitative measurement of PEG on
      PEGylated gold nanoparticles. The first, a displacement method, utilizes
      dithiothreitol to displace PEG from the gold surface. The dithiothreitol-coated
      gold nanoparticles are separated from the mixture via centrifugation, and the
      excess dithiothreitol and dissociated PEG are separated through reversed-phase
      high-performance liquid chromatography (RP-HPLC). The second, a dissolution
      method, utilizes potassium cyanide to dissolve the gold nanoparticles and
      liberate PEG. Excess CN(-), Au(CN)2 (-), and free PEG are separated using RP
      HPLC. In both techniques, the free PEG can be quantified against a standard curve
      using charged aerosol detection. The displacement and dissolution methods are
      validated here using 2-, 5-, 10-, and 20-kDa PEGylated 30-nm colloidal gold
      nanoparticles. Further value in these techniques is demonstrated not only by
      quantitating the total PEG fraction but also by being able to be adapted to
      quantitate the free unbound PEG and the bound PEG fractions. This is an important
      distinction, as differences in the bound and unbound PEG fractions can affect
      biocompatibility, which would not be detected in techniques that only quantitate
      the total PEG fraction. 

PMID- 25749799
TI  - Synthesis of magnetic molecularly imprinted polymers for the selective separation
      and determination of metronidazole in cosmetic samples.
AB  - In this study, novel magnetic molecularly imprinted polymers (MMIPs) were
      developed as a sorbent for solid-phase extraction (SPE) and used for the
      selective separation of metronidazole (MNZ) in cosmetics; MNZ was detected by
      high-performance liquid chromatography (HPLC). First, magnetic Fe3O4
      nanoparticles (NPs) were prepared by the co-precipitation of Fe(2+)and Fe(3+)
      ions in an ammonia solution; then oleic acid (OA) was modified onto the surface
      of Fe3O4NPs. Finally, the MMIP was prepared by aqueous suspension polymerization,
      involving the copolymerization of Fe3O4NPs@OA with MNZ as the template molecule,
      methacrylic acid (MAA) as the functional monomer, ethylene glycol maleic rosinate
      acrylate (EGMRA) as the cross-linking agent, and 2,2-azobisisobutyronitrile
      (AIBN) as the initiator. The MMIP materials showed high selective adsorption
      capacity and fast binding kinetics for MNZ; the maximum adsorption amount of the
      MMIP to MNZ was 46.7 mg/g. The assay showed a linear range from 0.1 to 20.0
      MUg/mL for MNZ with the correlation coefficient 0.999. The relative standard
      deviations (RSD) of intra- and inter-day ranging from 0.71 to 2.45% and from 1.06
      to 5.20% were obtained. The MMIP can be applied to the enrichment and
      determination of MNZ in cosmetic products with the recoveries of spiked toner,
      powder, and cream cosmetic samples ranging from 90.6 to 104.2, 84.1 to 91.4, and
      90.3 to 100.4%, respectively, and the RSD was <3.54%.

PMID- 25749800
TI  - Time perception and the experience of agency.
AB  - In the current study, we investigate whether sense of agency over an effect
      coincides with the perceived time of the effect that occurs either at its usual
      time or earlier or later than usual. One group of participants usually perceived
      an action effect immediately after the action, another group delayed by 250 ms.
      In test blocks the effect stimulus was sometimes presented earlier or later than
      usual. Participants judged either the degree of experienced agency over the
      effect or whether the effect had appeared at its usual time, or earlier or later
      than usual. In both groups experienced agency and the perception of the effect's
      time 'as usual' were highly correlated. To rule out that time judgments
      influenced sense of agency, we replicated the pattern of agency judgments in
      Experiment 2 in which participants only judged agency. Taken together, we
      demonstrated that agency and time judgments vary similarly across temporal
      deviations of effects irrespective of to which delay participants were adapted
      to. The high correlation of judgment types indicates that perceiving an effect at
      its usual time and sensing to have caused the effect are closely related. In
      contrast, physical temporal proximity of actions and effects has only a minor
      impact on experienced agency. 

PMID- 25749801
TI  - Haptic computer-assisted patient-specific preoperative planning for orthopedic
      fractures surgery.
AB  - PURPOSE: The aim of orthopedic trauma surgery is to restore the anatomy and
      function of displaced bone fragments to support osteosynthesis. For complex
      cases, including pelvic bone and multi-fragment femoral neck and distal radius
      fractures, preoperative planning with a CT scan is indicated. The planning
      consists of (1) fracture reduction-determining the locations and anatomical sites
      of origin of the fractured bone fragments and (2) fracture fixation-selecting and
      placing fixation screws and plates. The current bone fragment manipulation,
      hardware selection, and positioning processes based on 2D slices and a computer
      mouse are time-consuming and require a technician. METHODS: We present a novel 3D
      haptic-based system for patient-specific preoperative planning of orthopedic
      fracture surgery based on CT scans. The system provides the surgeon with an
      interactive, intuitive, and comprehensive, planning tool that supports fracture
      reduction and fixation. Its unique features include: (1) two-hand haptic
      manipulation of 3D bone fragments and fixation hardware models; (2) 3D
      stereoscopic visualization and multiple viewing modes; (3) ligaments and pivot
      motion constraints to facilitate fracture reduction; (4) semiautomatic and
      automatic fracture reduction modes; and (5) interactive custom fixation plate
      creation to fit the bone morphology. RESULTS: We evaluate our system with two
      experimental studies: (1) accuracy and repeatability of manual fracture reduction
      and (2) accuracy of our automatic virtual bone fracture reduction method. The
      surgeons achieved a mean accuracy of less than 1 mm for the manual reduction and
      1.8 mm (std [Formula: see text] 1.1 mm) for the automatic reduction. CONCLUSION:
      3D haptic-based patient-specific preoperative planning of orthopedic fracture
      surgery from CT scans is useful and accurate and may have significant advantages
      for evaluating and planning complex fractures surgery.

PMID- 25749803
TI  - Use of adjectives in abstracts when reporting results of randomized, controlled
      trials from industry and academia.
AB  - OBJECTIVE: Accurate representation of study findings is crucial to preserve
      public trust. The language used to describe results could affect perceptions of
      the efficacy or safety of interventions. We sought to compare the adjectives used
      in clinical trial reports of industry-authored and non-industry-authored
      research. METHODS: We included studies in PubMed that were randomized trials and
      had an abstract. Studies were classified as "non-industry-authored" when all
      authors had academic or governmental affiliations, or as "industry-authored" when
      any of the authors had industry affiliations. Abstracts were analyzed using a
      part-of-speech tagger to identify adjectives. To reduce the risk of false
      positives, the analysis was restricted to adjectives considered relevant to
      "coloring" (influencing interpretation) of trial results. Differences between
      groups were determined using exact tests, stratifying by journal. RESULTS: A
      total of 306,007 publications met the inclusion criteria. We were able to
      classify 16,789 abstracts; 9,085 were industry-authored research, and 7,704 were
      non-industry-authored research. We found a differential use of adjectives between
      industry-authored and non-industry-authored reports. Adjectives such as "well
      tolerated" and "meaningful" were more commonly used in the title or conclusion of
      the abstract by industry authors, while adjectives such as "feasible" were more
      commonly used by non-industry authors. CONCLUSIONS: There are differences in the
      adjectives used when study findings are described in industry-authored reports
      compared with non-industry-authored reports. Authors should avoid overusing
      adjectives that could be inaccurate or result in misperceptions. Editors and peer
      reviewers should be attentive to the use of adjectives and assess whether the
      usage is context appropriate.

PMID- 25749802
TI  - The role of stem cell therapies in degenerative lumbar spine disease: a review.
AB  - Degenerative conditions of the lumbar spine are extremely common. Ninety percent
      of people over the age of 60 years have degenerative change on imaging; however,
      only a small minority of people will require spine surgery (Hicks et al. Spine
      (Phila Pa 1976) 34(12):1301-1306, 2009). This minority, however, constitutes a
      core element of spinal surgery practice. Whilst the patient outcomes from spinal
      surgeries have improved in recent years, some patients will remain with pain and
      disability despite technically successful surgery. Advances in regenerative
      medicine and stem cell therapies, particularly the use of mesenchymal stem cells
      and allogeneic mesenchymal precursor cells, have led to numerous clinical trials
      utilising these cell-based therapies to treat degenerative spinal conditions.
      Through cartilage formation and disc regeneration, fusion enhancement or via
      modification of pain pathways, stem cells are well suited to enhance spinal
      surgery practice. This review will focus on the outcomes of lumbar spinal
      procedures and the role of stem cells in the treatment of degenerative lumbar
      conditions to enhance clinical practice. The current status of clinical trials
      utilising stem cell therapies will be discussed, providing clinicians with an
      overview of the various cell-based treatments likely to be available to patients
      in the near future.

PMID- 25749804
TI  - Budget impact analysis of warfarin reversal therapies among hip fracture patients
      in Finland.
AB  - BACKGROUND: Hip fractures require operation within 36-48 h, and they are most
      common in the elderly. A high International Normalized Ratio should be corrected
      before surgery. In the current study, we analyzed the budget impact of various
      warfarin reversal approaches. METHODS: Four reversal strategies were chosen for
      the budget impact analysis: the temporary withholding of warfarin, administration
      of vitamin K, fresh frozen plasma (FFP), and a four-factor prothrombin complex
      concentrate (PCC). RESULTS: We estimated that, annually, 410 hip fracture
      patients potentially require warfarin reversal in Finland. The least costly
      treatment was vitamin K, which accounted for ?289,000 in direct healthcare costs,
      and the most costly treatment option was warfarin cessation, which accounted for
      ?1,157,000. In the budget impact analysis, vitamin K, PCC and FFP would be cost
      saving to healthcare compared with the current treatment mix. CONCLUSION: The
      various warfarin reversal strategies have different onset times, which may
      substantially impact the subsequent healthcare costs.

PMID- 25749805
TI  - Hydrophilic polymer embolism: an underrecognized iatrogenic cause of ischemia,
      inflammation, and coagulopathy.

PMID- 25749806
TI  - Risk of and risk factors for hypoglycemia and associated arrhythmias in patients
      with type 2 diabetes and cardiovascular disease: a cohort study under real-world
      conditions.
AB  - AIMS: Severe hypoglycemia is one of the strongest predictors of adverse clinical
      outcomes in patients with type 2 diabetes. Our study addressed the question
      whether there is a relationship between hypoglycemic events (HE) and severe
      cardiac arrhythmias in type 2 diabetic patients with established clinical risk
      factors under real-world conditions. METHODS: We included 94 patients with type 2
      diabetes and documented cardiovascular disease, in which interstitial glucose
      values and Holter ECG were recorded for 5 days in parallel. Patients received a
      stable treatment with insulin and/or sulfonylurea and were instructed to record
      symptoms of hypoglycemia or arrhythmias. RESULTS: Continuous glucose monitoring
      revealed 54 HE (interstitial glucose <3.1 mmol/l) in a total of 26 patients.
      Patients perceived only 39 % of HE during the day and 11 % of HE during the
      night. Patients with HE had a significantly higher number of severe ventricular
      arrhythmias [ventricular tachycardia (VT) 32.8 +/- 60 vs. 0.9 +/- 4.2, p =
      0.019], and multivariate regression analysis revealed the duration of severe HE
      and TSH level as independent predictors of the occurrence of a VT. CONCLUSIONS:
      In conclusion, our study suggests that hypoglycemia might be able to trigger at
      least under certain circumstances, such as low TSH, ventricular arrhythmias under
      real-world conditions. The large number of unrecognized HE and VT in vulnerable
      patients treated with insulin or sulfonylurea should encourage the practitioner
      to focus on stable glucose control and to search for silent HE.

PMID- 25749807
TI  - Exhaled methane concentration profiles during exercise on an ergometer.
AB  - Exhaled methane concentration measurements are extensively used in medical
      investigation of certain gastrointestinal conditions. However, the dynamics of
      endogenous methane release is largely unknown. Breath methane profiles during
      ergometer tests were measured by means of a photoacoustic spectroscopy based
      sensor. Five methane-producing volunteers (with exhaled methane level being at
      least 1 ppm higher than room air) were measured. The experimental protocol
      consisted of 5 min rest--15 min pedalling (at a workload of 75 W)--5 min rest. In
      addition, hemodynamic and respiratory parameters were determined and compared to
      the estimated alveolar methane concentration. The alveolar breath methane level
      decreased considerably, by a factor of 3-4 within 1.5 min, while the estimated
      ventilation-perfusion ratio increased by a factor of 2-3. Mean pre-exercise and
      exercise methane concentrations were 11.4 ppm (SD:7.3) and 2.8 ppm (SD:1.9),
      respectively. The changes can be described by the high sensitivity of exhaled
      methane to ventilation-perfusion ratio and are in line with the Farhi equation.

PMID- 25749808
TI  - Post partial nephrectomy surveillance imaging: an evidence-based approach.
AB  - To ensure the early detection of recurrent disease, all patients should undergo
      routine surveillance following partial nephrectomy for renal cell carcinoma. In
      order to optimize resource allocation and avoid unnecessary radiation exposure,
      the frequency and duration of surveillance should be tailored to the individual
      patient's risk of cancer recurrence. The evidence for surveillance after partial
      nephrectomy is presented reviewing the current literature on prognostic models
      and proposed surveillance protocols based on the timing and patterns of renal
      cell carcinoma recurrence. In addition, we review recent guidelines on post
      partial nephrectomy surveillance as well as the literature on novel imaging
      techniques that may aid in early disease discovery.

PMID- 25749809
TI  - Lack of Evidence That Male Fetal Microchimerism is Present in Endometriosis.
AB  - INTRODUCTION: Fetal microchimerism has been implicated in the etiology of
      autoimmune diseases. This study was done to test the hypothesis that male fetal
      microchimerism is present in eutopic and ectopic endometrium (EM) obtained from
      women with endometriosis but not in eutopic EM from women without endometriosis.
      METHODS: A total of 31 patients were selected, including women with endometriosis
      (paired eutopic and ectopic EM; n = 19) and women without endometriosis (eutopic
      EM; n = 12). Tricolor interphase fluorescence in situ hybridization analysis was
      performed by cohybridization of CEP Y SpectrumAqua and CEP X SpectrumGreen
      (SG)/CEP Y SpectrumOrange probes. RESULTS: Ectopic EM from women with
      endometriosis had 75% XX chromosomes (double SG signals) and 25% X chromosomes
      (single SG signal). Y chromosomes were not observed in any of the eutopic/ectopic
      endometrial tissues from cases or controls. CONCLUSIONS: We were unable to
      confirm our hypothesis that male fetal microchimerism is present in eutopic
      and/or ectopic EM obtained from women with endometriosis.

PMID- 25749810
TI  - Evaluation of Trastuzumab Anti-Tumor Efficacy and its Correlation with HER-2
      Status in Patient-Derived Gastric Adenocarcinoma Xenograft Models.
AB  - The aim of the study was to investigate trastuzumab anti-tumor efficacy and its
      correlation with HER-2 status in primary xenograft models derived from Chinese
      patients with gastric adenocarcinoma. Patient-derived gastric adenocarcinoma
      xenograft (PDGAX) mouse models were firstly generated by implanting gastric
      adenocarcinoma tissues from patients into immune deficient mice. A high degree of
      histological and molecular similarity between the PDGAX mouse models and their
      corresponding patients' gastric adenocarcinoma tissues was shown by pathological
      observation, HER-2 expression, HER-2 gene copy number, and mutation detection.
      Based on Hoffmann's criteria in gastric cancer, three models (PDGAX001, PDGAX003
      and PDGAX005) were defined as HER-2 positive with fluorescence in situ
      hybridization (FISH) amplification or immunohistochemistry (IHC) 2+/ 3+, while
      two models (PDGAX002, PDGAX004) were defined as HER-2 negative. Upon trastuzumab
      treatment, significant tumor regression (105 % TGI) was observed in model
      PDGAX005 (TP53 wt), while moderate sensitivity (26 % TGI) was observed in
      PDGAX003, and resistance was observed in PDGAX001, 002 and 004. A significant
      increase in HER-2 gene copy number was only observed in PDGAX005 (TP53 wt).
      Interestingly, trastuzumab showed no efficacy in PDGAX001 (HER2 IHC 3+ and FISH
      amplification, but with mutant TP53). Consistent with this finding, phosphor-HER2
      modulation by trastuzumab was observed in model PDGAX005, but not in PDGAX001.

PMID- 25749812
TI  - Infected patent foramen ovale (PFO).

PMID- 25749811
TI  - Sensitivity of Melanoma Cells to EGFR and FGFR Activation but Not Inhibition is
      Influenced by Oncogenic BRAF and NRAS Mutations.
AB  - BRAF and NRAS are the two most frequent oncogenic driver mutations in melanoma
      and are pivotal components of both the EGF and FGF signaling network.
      Accordingly, we investigated the effect of BRAF and NRAS oncogenic mutation on
      the response to the stimulation and inhibition of epidermal and fibroblast growth
      factor receptors in melanoma cells. In the three BRAF mutant, two NRAS mutant and
      two double wild-type cell lines growth factor receptor expression had been
      verified by qRT-PCR. Cell proliferation and migration were determined by the
      analysis of 3-days-long time-lapse videomicroscopic recordings. Of note, a more
      profound response was found in motility as compared to proliferation and double
      wild-type cells displayed a higher sensitivity to EGF and FGF2 treatment when
      compared to mutant cells. Both baseline and induced activation of the growth
      factor signaling was assessed by immunoblot analysis of the phosphorylation of
      the downstream effectors Erk1/2. Low baseline and higher inducibility of the
      signaling pathway was characteristic in double wild-type cells. In contrast,
      oncogenic BRAF or NRAS mutation did not influence the response to EGF or FGF
      receptor inhibitors in vitro. Our findings demonstrate that the oncogenic
      mutations in melanoma have a profound impact on the motogenic effect of the
      activation of growth factor receptor signaling. Since emerging molecularly
      targeted therapies aim at the growth factor receptor signaling, the appropriate
      mutational analysis of individual melanoma cases is essential in both preclinical
      studies and in the clinical trials and practice. 

PMID- 25749813
TI  - Use of Model-Based Iterative Reconstruction (MBIR) in reduced-dose CT for routine
      follow-up of patients with malignant lymphoma: dose savings, image quality and
      phantom study.
AB  - OBJECTIVES: To evaluate both in vivo and in phantom studies, dose reduction, and
      image quality of body CT reconstructed with model-based iterative reconstruction
      (MBIR), performed during patient follow-ups for lymphoma. METHODS: This study
      included 40 patients (mean age 49 years) with lymphoma. All underwent reduced
      dose CT during follow-up, reconstructed using MBIR or 50 % advanced statistical
      iterative reconstruction (ASIR). All had previously undergone a standard dose CT
      with filtered back projection (FBP) reconstruction. The volume CT dose index
      (CTDIvol), the density measures in liver, spleen, fat, air, and muscle, and the
      image quality (noise and signal to noise ratio, SNR) (ANOVA) observed using
      standard or reduced-dose CT were compared both in patients and a phantom study
      (Catphan 600) (Kruskal Wallis). RESULTS: The CTDIvol was decreased on reduced
      dose body CT (4.06 mGy vs. 15.64 mGy p < 0.0001). SNR was higher in reduced-dose
      CT reconstructed with MBIR than in 50 % ASIR or than standard dose CT with FBP
      (patients, p <= 0.01; phantoms, p = 0.003). Low contrast detectability and
      spatial resolution in phantoms were not altered on MBIR-reconstructed CT (p >=
      0.11). CONCLUSION: Reduced-dose CT with MBIR reconstruction can decrease
      radiation dose delivered to patients with lymphoma, while keeping an image
      quality similar to that obtained on standard-dose CT. KEY POINTS: * In lymphoma
      patients, CT dose reduction is a major concern. * Reduced-dose body CT provides a
      fourfold radiation dose reduction. * Optimized CT reconstruction techniques
      (MBIR) can maintain image quality.

PMID- 25749815
TI  - Is there an appropriate time to initiate the rehabilitation of human gametes
      destined for human ARTs?

PMID- 25749814
TI  - Porcine EEF1A1 and EEF1A2 genes: genomic structure, polymorphism, mapping and
      expression.
AB  - Eukaryotic translation elongation factor 1 alpha (EEF1A) plays a key role in
      protein synthesis. In higher vertebrates EEF1A occurs in two isoforms, EEF1A1 and
      EEF1A2, encoded by distinct genes. The purpose of this study was to compare the
      two porcine genes as for the genomic sequence, gene organization and mRNA
      expression in different tissues, as well as to search for polymorphism and
      chromosomal assignment. Standard methods of DNA and mRNA analysis were used. We
      determined the complete genomic sequence of the porcine EEF1A1 and EEF1A2 genes.
      The two genes differ in the lengths of transcription units (3102 and 8588 bp,
      respectively), but have similar genomic organization and their coding sequences
      are highly similar (78% identity of coding sequences and 92.4% identity of amino
      acid sequences). Several polymorphisms in the two genes were detected. EEF1A1 and
      EEF1A2 were mapped to SSC1p11.1 and SSC17q23.3, respectively. mRNA of EEF1A1 was
      expressed in all studied tissues (the highest expression was in 44-day fetal
      muscle and low expression in adult liver and brain), while EEF1A2 was expressed
      only in skeletal-muscle, tongue, heart, diaphragm and brain tissues. EEF1A2 was
      not expressed in fetal muscle tissue (44 days). In this paper results are
      provided on genomic sequences, genomic organization, polymorphism, chromosomal
      assignment and spatial and temporal expressions of the porcine EEF1A1 and EEF1A2
      genes. Novel polymorphisms were described in both genes. Porcine EEF1A2 was
      studied for the first time.

PMID- 25749816
TI  - Molecular Genetic Diagnosis of a Bethlem Myopathy Family with an Autosomal
      Dominant COL6A1 Mutation, as Evidenced by Exome Sequencing.
AB  - BACKGROUND: We describe herein the application of whole exome sequencing (WES)
      for the molecular genetic diagnosis of a large Korean family with dominantly
      inherited myopathy. CASE REPORT: The affected individuals presented with slowly
      progressive proximal weakness and ankle contracture. They were initially
      diagnosed with limb-girdle muscular dystrophy (LGMD) based on clinical and
      pathologic features. However, WES and subsequent capillary sequencing identified
      a pathogenic splicing-site mutation (c.1056+1G>A) in COL6A1, which was previously
      reported to be an underlying cause of Bethlem myopathy. After identification of
      the genetic cause of the disease, careful neurologic examination revealed subtle
      contracture of the interphalangeal joint in the affected members, which is a
      characteristic sign of Bethlem myopathy. Therefore, we revised the original
      diagnosis from LGMD to Bethlem myopathy. CONCLUSIONS: This is the first report of
      identification of COL6A1-mediated Bethlem myopathy in Korea, and indicates the
      utility of WES for the diagnosis of muscular dystrophy.

PMID- 25749817
TI  - The Overlap between Fibromyalgia Syndrome and Myotonia Congenita.
AB  - BACKGROUND: Fibromyalgia syndrome (FMS) is a complex disorder characterized by
      chronic widespread pain (CWP), multiple areas of tenderness, sleep disturbance,
      fatigue, and mood or cognitive dysfunction. Myotonia congenita (MC) is an
      inherited myopathic disorder that is caused by mutations in the gene encoding the
      skeletal muscle chloride channel, which can infrequently manifest as generalized
      muscle cramps or myalgia. CASE REPORT: The first case was a 33-year-old woman who
      complained of CWP and chronic headache occurring during pregnancy, and the second
      case was a 37-year-old man with CWP and depression who suffered from cold-induced
      muscle cramps. These two patients were initially diagnosed with FMS by
      rheumatologists, based on CWP of longer than 3 months duration and mechanical
      tenderness in specific body regions. However, these two FMS patients were
      subsequently also diagnosed with MC. CONCLUSIONS: These two cases are the first
      report of an overlap of CWP between FMS and MC.

PMID- 25749818
TI  - Congenital horner syndrome with heterochromia iridis associated with ipsilateral
      internal carotid artery hypoplasia.
AB  - BACKGROUND: Horner syndrome (HS), also known as Claude-Bernard-Horner syndrome or
      oculosympathetic palsy, comprises ipsilateral ptosis, miosis, and facial
      anhidrosis. CASE REPORT: We report herein the case of a 67-year-old man who
      presented with congenital HS associated with ipsilateral hypoplasia of the
      internal carotid artery (ICA), as revealed by heterochromia iridis and confirmed
      by computed tomography (CT). CONCLUSIONS: CT evaluation of the skull base is
      essential to establish this diagnosis and distinguish aplasia from
      agenesis/hypoplasia (by the absence or hypoplasia of the carotid canal) or from
      acquired ICA obstruction as demonstrated by angiographic CT.

PMID- 25749819
TI  - Abnormal Head Impulse Test in a Unilateral Cerebellar Lesion.
AB  - BACKGROUND: The findings of head impulse tests (HIT) are usually normal in
      cerebellar lesions. CASE REPORT: A 46-year-old male presented with progressive
      dizziness and imbalance of 3 weeks duration. The patient exhibited catch-up
      saccades during bedside horizontal HIT to either side, which was more evident
      during the rightward HIT. However, results of bithermal caloric tests and
      rotatory chair test were normal. MRI revealed a lesion in the inferior cerebellum
      near the flocculus. CONCLUSIONS: This case provides additional evidence that
      damage to the flocculus or its connections may impair the vestibulo-ocular reflex
      only during high-speed stimuli, especially when the stimuli are applied to the
      contralesional side. By observing accompanying cerebellar signs, the abnormal HIT
      findings caused by a cerebellar disorder can be distinguished from those produced
      by peripheral vestibular disorders.

PMID- 25749820
TI  - Recurrent Cardioembolic Stroke Treated Successfully with Repeated Mechanical
      Thrombectomy within the Acute Index Stroke Period.
AB  - BACKGROUND: The safety of repeated mechanical thrombectomy within the acute
      stroke period has not yet been clearly demonstrated. We describe herein a patient
      who was successfully treated with repeated mechanical thrombectomy within the
      acute index stroke period. CASE REPORT: A 50-year-old woman with atrial
      fibrillation presented with left-sided weakness caused by occlusion of the right
      middle cerebral artery (MCA). Emergent mechanical thrombectomy with the Solitaire
      device achieved complete recanalization. The left MCA occlusion redeveloped at 6
      days after the first treatment, at which time her international normalized ratio
      (INR) was 2.3. Endovascular thrombectomy was reattempted rapidly and complete
      recanalization was achieved again. Her neurologic symptoms resolved after the
      thrombectomy. CONCLUSIONS: This case demonstrates that repeated mechanical
      thrombectomy can be safely and successfully performed even in a patient with a
      high INR and a recurrent stroke during the acute period after the index stroke.

PMID- 25749821
TI  - The Need for a Coagulation Assay after Initiation of New Oral Anticoagulants in
      Patients with Renal Dysfunction: A Case Report.
AB  - BACKGROUND: Dabigatran etexilate, a new oral anticoagulant, was recently approved
      as an efficacious alternative to warfarin for the prevention of first and
      recurrent stroke in patients with nonvalvular atrial fibrillation. Limited data
      are available for dabigatran use in patients with a creatinine clearance rate
      (CrCL) of 15-30 mL/min. Furthermore, current guidelines do not recommend frequent
      blood monitoring after dabigatran use. We report herein a patient with severe
      renal dysfunction who exhibited profound coagulopathy after 2 days of dabigatran
      use. CASE REPORT: An 87-year-old woman was admitted for altered mental status and
      left-side weakness. She was diagnosed with right middle cerebral artery
      infarction. The baseline assessment revealed a serum creatinine concentration of
      1.29 mg/dL and a CrCL of 27.2 mL/min. Dabigatran therapy was started 5 weeks
      after admission at a dosage of 110 mg twice daily. After 2 days of dabigatran
      use, the patient developed multiple bruises and evidence of upper
      gastrointestinal bleeding. Laboratory tests demonstrated a severe coagulopathy,
      with a prothrombin time of 85.9 sec, an international normalized ratio of 11.36,
      an activated partial thromboplastin time of 119.2 sec, and a thrombin time of
      230.8 sec. Serial assessment of the patient's renal function revealed substantial
      fluctuation of the CrCL (range, 17.9-26.5 mL/min). CONCLUSIONS: The present case
      emphasizes the need for frequent checking of renal function and assessment using
      coagulation assays after commencing dabigatran therapy in patients with moderate
      to-severe renal impairment.

PMID- 25749822
TI  - A Novel F45S SOD1 Mutation in Amyotrophic Lateral Sclerosis Coexisting with
      Bullous Pemphigoid.
AB  - BACKGROUND: The coexistence of an autoimmune disease and amyotrophic lateral
      sclerosis (ALS) has led to the hypothesis that immune-mediated pathological
      mechanisms are overlapping in the two diseases. We report herein a rare
      coexistence of bullous pemphigoid (BP) in a novel mutation (F45S) of the gene
      encoding Cu/Zn superoxide dismutase (SOD1) in an ALS patient, and discuss a role
      for the SOD1 mutation in this unusual overlap. CASE REPORT: A 57-year-old male
      with familial ALS, including vesicles and tense bullae on erythematous bases, was
      diagnosed with BP. Direct immunofluorescence revealed deposits of C3 and
      immunoglobulin G in the basement membrane zone. Direct sequencing of SOD1 in the
      patient revealed a novel mutation (c.137T>C; F45S). CONCLUSIONS: We report a
      novel SOD1 mutation in ALS, which was combined with BP. This novel SOD1 mutation
      could affect the phenotype of a combined autoimmune disease and matrix
      metalloproteinase-9. There may therefore be common factors linking BP and ALS
      with the SOD1 mutation.

PMID- 25749823
TI  - Autoantibody-Mediated Sensory Polyneuropathy Associated with Indolent B-Cell Non
      Hodgkin's Lymphoma: A Report of Two Cases.
AB  - BACKGROUND AND PURPOSE: Abnormalities of the peripheral nervous system occur in
      5% of patients with lymphoma. Polyneuropathy has not been described in patients
      with mantle-cell and marginal-zone B-cell lymphomas. CASE REPORT: Two elderly
      patients with indolent non-Hodgkin's lymphoma developed a progressive sensory
      polyneuropathy that was associated with serum autoantibodies directed against
      asialosyl/sialosyl gangliosides and myelin-associated glycoprotein/sulfated
      glucuronyl paragloboside, respectively, which are peripheral-nerve antigens. The
      oligoclonal pattern of these antibodies hinted at a lymphoma-induced immune
      dysregulation. The neuropathy stabilized clinically during treatment with
      intravenous immunoglobulin G. B-cell lymphoma was managed with a "watchful
      waiting" approach. CONCLUSIONS: The concept of antigen-specific, immune-mediated
      neuropathy associated with slow-growing lymphoma of mature B-cells may be
      underrecognized. The principle of treating the illness underlying neuropathy may
      not be always indicated or necessary if risk-benefit and cost-benefit analyses
      are taken into account.

PMID- 25749824
TI  - EEG Source Imaging in Partial Epilepsy in Comparison with Presurgical Evaluation
      and Magnetoencephalography.
AB  - BACKGROUND AND PURPOSE: The aim of this study was to determine the usefulness of
      three-dimensional (3D) scalp EEG source imaging (ESI) in partial epilepsy in
      comparison with the results of presurgical evaluation, magnetoencephalography
      (MEG), and electrocorticography (ECoG). METHODS: The epilepsy syndrome of 27
      partial epilepsy patients was determined by presurgical evaluations. EEG
      recordings were made using 70 scalp electrodes, and the 3D coordinates of the
      electrodes were digitized. ESI images of individual and averaged spikes were
      analyzed by Curry software with a boundary element method. MEG and ECoG were
      performed in 23 and 9 patients, respectively. RESULTS: ESI and MEG source imaging
      (MSI) results were well concordant with the results of presurgical evaluations
      (in 96.3% and 100% cases for ESI and MSI, respectively) at the lobar level.
      However, there were no spikes in the MEG recordings of three patients. The ESI
      results were well concordant with MSI results in 90.0% of cases. Compared to
      ECoG, the ESI results tended to be localized deeper than the cortex, whereas the
      MSI results were generally localized on the cortical surface. ESI was well
      concordant with ECoG in 8 of 9 (88.9%) cases, and MSI was also well concordant
      with ECoG in 4 of 5 (80.0%) cases. The EEG single dipoles in one patient with
      mesial temporal lobe epilepsy were tightly clustered with the averaged dipole
      when a 3 Hz high-pass filter was used. CONCLUSIONS: The ESI results were well
      concordant with the results of the presurgical evaluation, MSI, and ECoG. The ESI
      analysis was found to be useful for localizing the seizure focus and is
      recommended for the presurgical evaluation of intractable epilepsy patients.

PMID- 25749826
TI  - Higher levels of reactive oxygen species are associated with anergy in chronic
      lymphocytic leukemia.

PMID- 25749825
TI  - Randomized trial of radiation-free central nervous system prophylaxis comparing
      intrathecal triple therapy with liposomal cytarabine in acute lymphoblastic
      leukemia.
AB  - Developing optimal radiation-free central nervous system prophylaxis is a
      desirable goal in acute lymphoblastic leukemia, to avoid the long-term toxicity
      associated with cranial irradiation. In a randomized, phase II trial enrolling
      145 adult patients, we compared intrathecal liposomal cytarabine (50 mg: 6/8
      injections in B-/T-cell subsets, respectively) with intrathecal triple therapy
      (methotrexate/cytarabine/prednisone: 12 injections). Systemic therapy included
      methotrexate plus cytarabine or L-asparaginase courses, with methotrexate
      augmented to 2.5 and 5 g/m(2) in Philadelphia-negative B- and T-cell disease,
      respectively. The primary study objective was the comparative assessment of the
      risk/benefit ratio, combining the analysis of feasibility, toxicity and efficacy.
      In the liposomal cytarabine arm 17/71 patients (24%) developed grade 3-4
      neurotoxicity compared to 2/74 (3%) in the triple therapy arm (P=0.0002), the
      median number of episodes of neurotoxicity of any grade was one per patient
      compared to zero, respectively (P=0.0001), and even though no permanent
      disabilities or deaths were registered, four patients (6%) discontinued
      intrathecal prophylaxis on account of these toxic side effects (P=0.06).
      Neurotoxicity worsened with liposomal cytarabine every 14 days (T-cell disease),
      and was improved by the adjunct of intrathecal dexamethasone. Two patients in the
      liposomal cytarabine arm suffered from a meningeal relapse (none with T-cell
      disease, only one after high-dose chemotherapy) compared to four in the triple
      therapy arm (1 with T-cell disease). While intrathecal liposomal cytarabine could
      contribute to improved, radiation-free central nervous system prophylaxis, the
      toxicity reported in this trial does not support its use at 50 mg and prompts the
      investigation of a lower dosage. (clinicaltrials.gov identifier: NCT-00795756). 

PMID- 25749827
TI  - The clinical significance of K-Cl cotransport activity in red cells of patients
      with HbSC disease.
AB  - HbSC disease is the second commonest form of sickle cell disease, with poorly
      understood pathophysiology and few treatments. We studied the role of K-Cl
      cotransport activity in determining clinical and laboratory features, and
      investigated its potential role as a biomarker. Samples were collected from 110
      patients with HbSC disease and 41 with sickle cell anemia (HbSS). K-Cl
      cotransport activity was measured in the oxygenated (K-Cl cotransport(100)) and
      deoxygenated (K-Cl cotransport(0)) states, using radioactive tracer studies. K-Cl
      cotransport activity was high in HbSC and decreased significantly on
      deoxygenation. K-Cl cotransport activity correlated significantly and positively
      with the formation of sickle cells. On multiple regression analysis, K-Cl
      cotransport increased significantly and independently with increasing
      reticulocyte count and age. K-Cl cotransport activity was increased in patients
      who attended hospital with acute pain in 2011 compared to those who did not (K-Cl
      cotransport(100): mean 3.87 versus 3.20, P=0.009, independent samples T-test; K
      Cl cotransport(0): mean 0.96 versus 0.68, P=0.037). On logistic regression only K
      Cl cotransport was associated with hospital attendance. Increased K-Cl
      cotransport activity was associated with the presence of retinopathy, but this
      effect was confounded by age. This study links variability in a fundamental
      aspect of cellular pathology with a clinical outcome, suggesting that K-Cl
      cotransport is central to the pathology of HbSC disease. Increased K-Cl
      cotransport activity is associated with increasing age, which may be of
      pathophysiological significance. Effective inhibition of K-Cl cotransport
      activity is likely to be of therapeutic benefit.

PMID- 25749828
TI  - Regulatory T cells and progenitor B cells are independent prognostic predictors
      in lower risk myelodysplastic syndromes.

PMID- 25749829
TI  - Somatic mutations of cell-free circulating DNA detected by next-generation
      sequencing reflect the genetic changes in both germinal center B-cell-like and
      activated B-cell-like diffuse large B-cell lymphomas at the time of diagnosis.

PMID- 25749831
TI  - The incidence of contrast medium-induced nephropathy following endovascular
      aortic aneurysm repair: assessment of risk factors.
AB  - PURPOSE: The aim of the study was to investigate the incidence of contrast medium
      induced nephropathy (CIN) and risk factors for CIN following endovascular
      abdominal aortic aneurysm repair or thoracic endovascular aortic aneurysm repair.
      MATERIALS AND METHODS: After exclusion criteria, 139 (121 males, 18 females)
      patients aged 20-86 (median 65.5) years who underwent endovascular aortic
      aneurysm repair between January 2002 and September 2013 were included in this
      retrospective study. CIN, with >=25% increase in serum creatinine levels within 3
      days after contrast medium administration, was compared to the patients'
      demographics, risk factors, type and complexity of the endovascular operation,
      parameters regarding to the contrast medium, preoperative estimated glomerular
      filtration rate (eGFR), and preoperative and early postoperative serum
      parameters. Statistical analyses were performed with Kolmogorov-Smirnov, chi (2)
      and Student's t tests. RESULTS: CIN, detected in 39 of 139 patients (28%), was
      correlated with preoperative eGFR <60 ml/min/1.73 m(2) (P = 0.04) and high
      preoperative and postoperative serum urea and creatinine levels. Postoperative
      serum urea levels (P < 0.001) were significant in multivariate analysis.
      CONCLUSION: In patients undergoing endovascular aortic aneurysm repair, CIN was
      correlated with preoperative and postoperative renal impairment, while it was not
      correlated with the contrast medium dose.

PMID- 25749830
TI  - Benefits of a 12-week lifestyle modification program including diet and combined
      aerobic and resistance exercise on albuminuria in diabetic and non-diabetic
      Japanese populations.
AB  - BACKGROUND: Albuminuria is a biomarker for chronic kidney disease and an
      independent predictor of cardiovascular and all-cause mortality. A recent meta
      analysis concluded that these risks increase with urinary albumin concentration,
      even when below the microalbuminuria threshold. Thus, minimizing urinary albumin
      may be a valuable therapeutic goal regardless of disease status. METHODS: We
      investigated the benefits and safety of a 12-week lifestyle modification program
      including diet and combined aerobic and resistance exercise for reducing
      albuminuria in 295 normoalbuminuric or microalbuminuric Japanese adults,
      including 30 with type 2 diabetes mellitus (T2DM), 104 with metabolic syndrome
      (MS), and 145 with hypertension (HT). RESULTS: In the study population, the
      urinary albumin:creatinine ratio (UACR) was reduced significantly (DeltaUACR -3.8
      +/- 16.8 mg/g, P < 0.001) with no change in estimated glomerular filtration rate
      (eGFR) (DeltaeGFR -0.4 +/- 7.4 mL/min/1.73 m(2), P = 0.343). The reduction in
      UACR was associated with decreased fasting plasma glucose (P < 0.05). The UACR
      was also reduced in the T2DM, MS, and HT groups with no change in eGFR. Reduced
      UACR was associated with decreased fasting plasma glucose in the MS group and
      decreased systolic blood pressure in the HT group. The UACR was also reduced in
      46 subjects using renin-angiotensin system inhibitors with no change in eGFR.
      CONCLUSIONS: Our 12-week lifestyle modification program reduced UACR, maintained
      eGFR, and improved multiple fitness findings in Japanese subjects including T2DM,
      MS, and HT patients.

PMID- 25749833
TI  - Ossification of the petrosphenoidal ligament: multidetector computed tomography
      findings of an unusual variation with a potential role in abducens nerve palsy.
AB  - PURPOSE: The petrosphenoidal ligament (PSL) forms the roof of Dorello's canal in
      which the abducens nerve courses. An ossified PSL may play a role in abducens
      nerve palsy although it is controversial. Therefore, we aimed to investigate the
      incidence and the imaging features of PSL ossification using multidetector
      computed tomography (MDCT). MATERIALS AND METHODS: Consecutive head CT scans,
      performed between January 2014 and May 2014, were retrospectively evaluated by
      two radiologists to look for a partial or complete ossification at the expected
      site of the PSL using axial, reformatted coronal and sagittal images. RESULTS: We
      found 46 patients (32 men, 14 women) with ossification of the PSL out of 523 head
      CT scans (46/523, 8.8%). A total of 61 PSL ossifications (31 unilateral; 15
      bilateral) were found in 1,046 petroclival regions (61/1,046, 5.8%). Of these 61
      ossifications, 34 (34/523, 6.5%) were on the right and 27 (27/523, 5.1%) were on
      the left; 38 (38/1,046, 3.6%) were classified as partial and 23 (23/1,046, 2.2%)
      were classified as complete. CONCLUSION: Ossification of the PSL is not a rare
      finding on MDCT. This imaging technique can reliably demonstrate the imaging
      features of an ossified PSL.

PMID- 25749832
TI  - "Cerebellar peduncle quarter notes" formed by the superior and middle cerebellar
      peduncles: comparison with a diffusion tensor study of spinocerebellar
      degeneration.
AB  - PURPOSE: To investigate morphological changes of the superior and middle
      cerebellar peduncles (SCP, MCP) in spinocerebellar degeneration (SCD) by
      observing "cerebellar peduncle quarter notes". MATERIALS AND METHODS: We examined
      21 patients with SCD, including nine patients with multiple system atrophy
      cerebellar type (MSA-C), and 24 controls. We measured SCP angle and performed
      diffusion tensor analysis to quantify the apparent diffusion coefficient (ADC)
      and fractional anisotropy (FA) of the MCP. We quantified the relationship between
      SCP angle and the ADC and FA of the MCP, and compared these variables between MSA
      C patients and controls. RESULTS: There was statistically significant negative
      correlation between SCP angle and FA of the MCP, and a positive correlation
      between SCP angle and the ADC of the MCP. Mean SCP angle was larger among MSA-C
      patients than among normal controls. CONCLUSIONS: SCP angle tended to be larger
      among patients with severe degeneration of the MCP. The SCP angle, quantified by
      observing "cerebellar peduncle quarter notes", may be a simple index for
      evaluation of degeneration of the MCP.

PMID- 25749834
TI  - [Between 100 and 200 years before the microbiome...].
AB  - Before the era of microbiote, our ancestors patiently discovered, described and
      cultivated pathogens, including those responsible for dermatoses. The very well
      known ectoparasites were represented in the earliest books on cutaneous diseases
      at the end of XVIII(th) century and the first half of the XIX(th) century. Fungi
      were discovered in the 1840s, rapidly followed by numerous bacteria, including
      those causing tuberculosis and lepra. This article is illustrated by images that
      often showed for the first time parasites and bacteria in books dedicated to
      cutaneous diseases. Engravings and photographs from the books of Willan, Rayer
      and Hardy show accurate images of pathogens. Microscopic images can also be found
      in the textbooks of Simon, Leloir, Sabouraud, Unna and many others. Darier
      himself believed that "Darier's disease" was due to a parasite, which explains
      why he named his disease "Vegetant follicular psorospermosis". 

PMID- 25749835
TI  - [Diversity of cutaneous bacteria decreases inflammation].
AB  - Human microbiota includes all microorganisms, saprophytes and pathogens that
      colonize our bodies. Recent advances in metagenomic analysis techniques have
      expanded our knowledge of the microbiota and fundamentally changed our view of
      its relationships with the immune system. The commensal flora appears to be
      essential to the development of the immune system, and the diversity of the
      microbiota is correlated with good health status of individuals. These findings
      open up new conceptual and therapeutic approaches in chronic inflammatory
      diseases. 

PMID- 25749836
TI  - [Skin microbiota and atopic dermatitis: toward new therapeutic options?].
AB  - The skin in patients with atopic dermatitis (AD) is constantly colonized by S.
      aureus, in part due to a deficit in epidermal antimicrobial peptides. S. aureus
      can cause secondary infections but is also involved in the occurrence and
      severity of the inflammatory flares of AD. Thus, the diversity of skin microbiota
      is abnormal in AD. Dynamic studies of the microbiota showed that the prevalence
      of staphylococcae sp. is further increased during flares of AD. This dysbiosis
      leads to an increase in inflammatory reactions in which staphylococcal toxins
      play an important role. Changes in the gut microbiota also play a role in the
      early maturation of the immune system and the occurrence of allergic reactions.
      Attempts in the modulation of skin microbiota have recently been made showing
      that a cream containing a lysate of a non pathogenic Gram negative bacteria, V.
      filiformis, is capable of improving the manifestations of AD. These effects may
      be driven by a regulation of skin innate immunity through Toll like receptors
      (TLR-2), the secretion of IL-10 and the induction of regulatory T cells. 

PMID- 25749837
TI  - Volatile S-nitrosothiols and the typical smell of cancer.
AB  - An unconventional approach to investigations into the identification of typical
      volatile emissions during illnesses gives rise to the proposal of a new class of
      cancer markers. Until now, cancer markers seem not to have been conclusively
      identified, though the obvious behavior of dogs points to their existence. The
      focus has been directed towards molecules containing sulfurous functionalities.
      Among such compounds, S-nitrosothiols (SNOs) are known to be involved in
      important physiological processes in living organisms and they are described as
      being typically elevated in cancer. Volatile SNOs (vSNOs) are proposed to be the
      source of the significant smell of cancer. Synthetic vSNOs are known to have
      lifetimes of between some minutes and several hours, which may be the main reason
      as to why they have been ignored until now, and also for the inability of
      analytics to detect them in vivo. Based on typical structures occurring in the
      volatile sulfur organics being emitted from human breath, four vSNOs have been
      synthesized and characterized by tandem mass spectrometry and gas
      chromatography/mass spectrometry. Simulating the relatively fatty consistency of
      cancer tissue by diluting the samples in n-decane, surprisingly reduces their
      tendency to decompose to lifetimes of weeks even at room temperature. A sniffer
      dog was trained with the synthetic vSNOs, and the results of the tests indicate
      that synthetic and cancer smells are very similar or even the same. The findings
      can be a clue for further target-oriented systematic optimization of existing
      sensitive measurement methods to prove vSNOs as cancer emissions and finally
      establish future methods for cancer diagnosis based on screening for this new
      class of volatile illness markers.

PMID- 25749838
TI  - Changes in autopsy rates among cancer patients and their impact on cancer
      statistics from a public health point of view: a longitudinal study from 1980 to
      2010 with data from Cancer Registry Zurich.
AB  - During the last decades, autopsy rates have dramatically decreased in many
      countries. The Cancer Registry Zurich, which exists since 1980, provides the
      opportunity to address to what extent the number of autopsies in cancer patients
      has changed over a longer period of time and how often autopsies provide a
      diagnosis of clinically undetected cancer. Data from the Cancer Registry Zurich
      consisting of 102,434 cancer cases among 89,933 deceased patients between 1980
      and 2010 were analyzed by means of descriptive statistics. The autopsy rate
      declined from 60 % in 1980 to 7 % in 2010. The total number of autopsies
      performed decreased from 1179 in 1986 to 220 in 2010. Furthermore, there was also
      a decline in the rate of newly detected tumours based on autopsy information. In
      1980, the rate of newly detected tumours through autopsy was 42 % compared with
      2010, when the rate had declined to 17 %. A consequence of the reduced autopsy
      rate is the reduction of incidental findings at autopsy in cancer registration.
      However, this reduction has not negatively affected the total incidence of
      cancer. It seems that the state-of-the-art diagnostic tools used for tumour
      detection are sufficiently reliable, allowing the scientific community to trust
      the quality of data provided by cancer registries in spite of decreasing autopsy
      rates.

PMID- 25749839
TI  - Glioblastoma after AVM radiosurgery. Case report and review of the literature.
AB  - BACKGROUND: Stereotactic radiosurgery (SRS) is considered to be a relatively safe
      procedure in cerebral arteriovenous malformation management. There are very few
      reported cases of SRS-associated/induced malignancies. METHODS: We show the case
      of a 21-year-old female who presented with a 21-mm(3) ruptured AVM in the right
      mesial frontocallosal region. Embolization and/or radiosurgery was proposed. She
      preferred radiosurgery. The AVM was treated with CyberKnife((r)) SRS. RESULTS:
      She presented behavior changes 6 years after SRS. MRI showed a right subcortical
      frontal lesion with increased perfusion, more consistent with high-grade glioma.
      The lesion's center was within the irradiated region of the previous SRS, having
      received an estimated radiation dose of 4 Gy. Pathological examination noted a
      hypercellular tumor showing astrocytic tumor cells with moderate pleomorphism in
      a fibrillary background, endothelial proliferation, and tumor necrosis surrounded
      by perinecrotic pseudopalisades. Numerous mitotic figures were seen. The
      appearances were those of glioblastoma, WHO grade IV, with neuronal
      differentiation. SRS-associated/-induced GBM after treatment of a large AM is
      exceptional. SRS-associated/-induced malignancies are mostly GBMs and occur on
      average after a latency of 9.4 years, within very low-dose peripheral regions as
      well as the full-dose regions; 33.3 % of patients were under 20 years at the time
      of SRS, and in 66 % the lesion treated was a vascular pathology. CONCLUSION:
      Although it is unlikely that the risk of radiation-induced cancer will change the
      current standard of practice, patients must be warned of this potential
      possibility before treatment.

PMID- 25749840
TI  - Visual outcomes after treatment of paraclinoid aneurysms: comparison of surgical
      and endovascular interventions.

PMID- 25749841
TI  - Pathogenesis of radiosurgery-induced cyst formation in patients with cerebral
      arteriovenous malformations.

PMID- 25749842
TI  - The ethics of "primo non nocere", professional responsibility and shared decision
      making in high-stakes neurosurgery.

PMID- 25749843
TI  - The association between time spent in sedentary behaviors and blood pressure: a
      systematic review and meta-analysis.
AB  - BACKGROUND AND OBJECTIVE: Sedentary behaviors, defined as waking behaviors with
      low energy expenditure while sitting, are positively associated with several
      adverse health outcomes. However, the association between sedentary behaviors and
      blood pressure (BP) is inconclusive. This study aimed to conduct a systematic
      review and meta-analysis on the association between time spent in sedentary
      behaviors and BP. METHODS: We searched PubMed, MEDLINE, and Web of Science for
      papers published before August 2014 that assessed the association between time
      spent in sedentary behaviors and BP. Studies on both adults and children were
      included. Only good quality studies were included. The pooled estimates of
      systolic BP (SBP) and diastolic BP (DBP) increase per hour of time spent in
      sedentary behaviors a day were computed using a fixed-effects model and a random
      effects model, respectively. Another pooled estimate of odds ratio per hour of
      time spent in sedentary behaviors a day on having high BP was computed using a
      fixed-effects model. A sub-group analysis was conducted for studies using self
      reported and objectively assessed time spent in sedentary behaviors separately.
      RESULTS: A total of 31 papers of good quality were included in the systematic
      review, 18 of which found no association between time spent in sedentary
      behaviors and BP (58.1%). A total of 28 papers were included in the meta
      analysis. Pooled effects showed that an additional hour of time spent in
      sedentary behaviors per day was associated with an increase of 0.06 mmHg (108,228
      participants, 95% CI 0.01-0.11, p = 0.01) of SBP and 0.20 mmHg (107,791
      participants, 95% CI 0.10-0.29, p < 0.001) of DBP. Accelerometer-assessed time
      spent in sedentary behaviors was not associated with either SBP (p = 0.06) or DBP
      (p = 0.33). The odds ratio (OR) of having high BP with an additional hour of time
      spent in sedentary behaviors per day was 1.02 (98,798 participants, 95% CI 1.003
      1.03, p = 0.02). CONCLUSIONS: Self-reported but not accelerometer-assessed time
      spent in sedentary behaviors was associated with BP. Further studies are
      warranted to determine the preventive effect of reducing sedentary behaviors on
      high BP.

PMID- 25749844
TI  - Type I IFN signaling on dendritic cells is required for NK cell-mediated anti
      tumor immunity.
AB  - NK cells play a vital role in innate anti-tumor immunity. Crosstalk between NK
      cells and dendritic cells (DCs) has come to the forefront in protection against
      tumors in the context of DC vaccines. We previously discovered that NK cell
      activation mediates the anti-tumor activity elicited by DC vaccines in response
      to melanoma tumor challenge in a murine lung metastasis model. In this study, we
      sought to explore the mechanism behind this NK-DC communication, specifically
      looking at the involvement of IL-15 and type I IFN signaling. Using DCs from IL
      15(-/-) and IL-15Ralpha(-/-) mice, we found that the anti-tumor effect of the
      vaccine remained comparable with DCs from wild type mice. Moreover, DCs derived
      from IFN-alpha/betaR(-/-) mice also maintained their anti-tumor effect.
      Interestingly, endogenous DCs were found to accumulate in the draining lymph
      nodes post-immunization and their depletion abolished the anti-tumor effect of
      the vaccine. Our findings suggest the important role that type I IFN signaling
      and endogenous DCs play in DC vaccine-mediated anti-tumor protection. Our data
      suggest that type I IFNs from vaccine DCs activate host DCs to provide NK cell
      mediated anti-tumor immunity. 

PMID- 25749845
TI  - Versicolols A and B, two new prenylated isocoumarins from endophytic fungus
      Aspergillus versicolor and their cytotoxic activity.
AB  - Versicolols A and B (1 and 2), two rare prenylated isocoumarin derivatives, along
      with five known isocoumarins (3-7) were isolated from the fermentation products
      of an endophytic fungus Aspergillus versicolor. Their structures were elucidated
      on the basis of extensive spectroscopic analysis, including 1D- and 2D-NMR
      techniques. Compounds 1 and 2 were evaluated for their cytotoxicity against five
      human tumor cell lines. The results showed that compounds 1 exhibited weak
      cytotoxicity against A549 and MCF7 cells with IC50 values of 9.4 and 8.8 MUm, and
      compound 2 exhibited weak cytotoxicity against SHSY5Y and MCF7 cells with IC50
      values of 8.2 and 6.8 MUm, respectively.

PMID- 25749846
TI  - Treatment of Meniere's Disease.
AB  - OPINION STATEMENT: Diagnosis of Meniere's disease is made with a characteristic
      patient history, including discrete episodes of vertigo lasting 20 min or longer,
      accompanied by sensorineural hearing loss, which is typically low frequency at
      first, aural fullness, and tinnitus. Workup includes audiometry, a contrast
      enhanced MRI of the internal auditory canals, and exclusion of other diseases
      that can produce similar symptoms, like otosyphilis, autoimmune inner ear
      disease, perilymphatic fistula, superior semicircular canal syndrome, Lyme
      disease, multiple sclerosis, vestibular paroxysmia, and temporal bone tumors. A
      history of migraine should be sought as well because of a high rate of co
      occurrence (Rauch, Otolaryngol Clin North Am 43:1011-1017, 2010). Treatment
      begins with conservative measures, including low salt diet, avoidance of stress
      and caffeine, and sleep hygiene. Medical therapy with a diuretic is the usual
      next step. If that fails to control symptoms, then the options of intratympanic
      (IT) steroids and betahistine are discussed. Next tier treatments include the
      Meniett device and endolymphatic sac surgery, but the efficacy of both is
      controversial. If the above measures fail to provide symptomatic control of
      vertigo, then ablative therapies like intratympanic gentamicin are considered.
      Rarely, vestibular nerve section or labyrinthectomy is considered for a patient
      with severe symptoms who does not show a reduction in vestibular function with
      gentamicin. Benzodiazepines and anti-emetics are used for symptomatic control
      during vertigo episodes. Rehabilitative options for unilateral vestibular
      weakness include physical therapy and for unilateral hearing loss include
      conventional hearing aids, contralateral routing of sound (CROS) and
      osseointegrated hearing aids.

PMID- 25749847
TI  - How treatment monitoring is influencing treatment decisions in glioblastomas.
AB  - OPINION STATEMENT: Glioblastoma (GBM), the most common malignant primary tumor in
      adults, carries a dismal prognosis with an average median survival of 14-16
      months. The current standard of care for newly diagnosed GBM consists of maximal
      safe resection followed by fractionated radiotherapy combined with concurrent
      temozolomide and 6 to 12 cycles of adjuvant temozolomide. The determination of
      treatment response and clinical decision-making in the treatment of GBM depends
      on accurate radiographic assessment. Differentiating treatment response from
      tumor progression is challenging and combines long-term follow-up using standard
      MRI, with assessing clinical status and corticosteroid dependency. At
      progression, bevacizumab is the mainstay of treatment. Incorporation of
      antiangiogenic therapies leads to rapid blood-brain barrier normalization with
      remarkable radiographic response often not accompanied by the expected survival
      benefit, further complicating imaging assessment. Improved radiographic
      interpretation criteria, such as the Response Assessment in Neuro-Oncology (RANO)
      criteria, incorporate non-enhancing disease but still fall short of definitely
      distinguishing tumor progression, pseudoresponse, and pseudoprogression. With new
      evolving treatment modalities for this devastating disease, advanced imaging
      modalities are increasingly becoming part of routine clinical care in a field
      where neuroimaging has such essential role in guiding treatment decisions and
      defining clinical trial eligibility and efficacy.

PMID- 25749848
TI  - Non-culprit coronary lesions in young patients have higher rates of
      atherosclerotic progression.
AB  - The present study aimed to investigate whether non-culprit coronary lesions
      (NCCLs) in young patients (<45 years) who underwent percutaneous coronary
      intervention (PCI) with stents have higher rates of atherosclerotic progression
      than older patients. Eight hundred and forty-eight consecutive patients who
      underwent successful PCI with stents and second coronary angiography in a single
      center from January 7, 2008 to May 7, 2013 were enrolled. NCCL progression was
      assessed using three-dimensional quantitative coronary angiography and was
      defined as >= 10% diameter reduction of preexisting stenoses of >= 50%, >= 30%
      diameter reduction of <50% stenoses, development of a new stenosis of >= 30% in a
      previously normal segment, or progression to total occlusion. The mean time
      interval between two catheterization was 10.79 months; 136 (16.0%) patients
      exhibited progression of NCCLs. Multivariate Cox regression analysis (stepwise)
      showed young age to be an independent determinant of NCCL progression. Compared
      with the older patients(>= 45 years), the crude hazard ratio (HR) for NCCL
      progression in the young patients(<45 years) was 2.17 (95% CI 1.42-3.30; P <
      0.001); the association remained significant after adjustment for sex, ST
      elevation myocardial infarction, body mass index, systolic and diastolic blood
      pressure, serum lipids, fasting blood glucose, smoking, drinking, hypertension,
      family history of coronary heart disease, diabetes mellitus, medication use and
      NCCL characteristics (adjusted HR 1.70, 95% CI 1.06-2.72; P = 0.029). NCCLs in
      young patients (<45 years) with coronary artery disease have high rates of
      atherosclerotic progression.

PMID- 25749849
TI  - Alternaria-Associated Fungus Ball of Orbit Nose and Paranasal Sinuses: Case
      Report of a Rare Clinical Entity.
AB  - Alternaria-associated fungus ball of maxillar, ethmoidal paranasal sinuses, nasal
      cavity and orbit with bone erosion is extremely rare. Till recently, only two
      cases of this infection in immune competitive patients have been reported. We are
      herein describing the case of immune-competent woman who suffered of nasal
      congestion for 10 years. Patient was treated for tumor-like lesion in right
      maxillar sinus, where propagation in right nose cavity, right ethmoidal cells and
      right orbita was present. The organism that was seen in surgical removal of
      fungal debris by histological study, in using mycological testing, was proven as
      Alternaria alternata. Combination of surgical intervention and treatment with
      itraconazole eradicated fungal infection, and the disease was not relapsed in
      follow-up period of 2 years.

PMID- 25749850
TI  - In vivo study of novelly formulated porcine-derived fibrinogen as an efficient
      sealant.
AB  - Fibrinogen has been used as surgical sealant in the clinical setting for decades.
      The application of human plasma-derived fibrinogen is limited due to high cost
      and the risk of prion and virus infection. We developed a novel arginine
      formulated fibrinogen from cryoprecipitates of porcine plasma. This porcine
      derived fibrinogen exhibited excellent stability during sterilization and better
      hemostatic efficacy than a leading commercial hemostatic product in a nonlethal
      hemorrhage model. Therefore, it has the potential to be more economical and
      readily available while having a decreased risk of human blood-borne pathogen
      transmission. 

PMID- 25749851
TI  - Delay-sensitive and delay-insensitive deconvolution perfusion-CT: similar
      ischemic core and penumbra volumes if appropriate threshold selected for each.
AB  - INTRODUCTION: Perfusion-CT (PCT) processing involves deconvolution, a
      mathematical operation that computes the perfusion parameters from the PCT time
      density curves and an arterial curve. Delay-sensitive deconvolution does not
      correct for arrival delay of contrast, whereas delay-insensitive deconvolution
      does. The goal of this study was to compare delay-sensitive and delay-insensitive
      deconvolution PCT in terms of delineation of the ischemic core and penumbra.
      METHODS: We retrospectively identified 100 patients with acute ischemic stroke
      who underwent admission PCT and CT angiography (CTA), a follow-up vascular study
      to determine recanalization status, and a follow-up noncontrast head CT (NCT) or
      MRI to calculate final infarct volume. PCT datasets were processed twice, once
      using delay-sensitive deconvolution and once using delay-insensitive
      deconvolution. Regions of interest (ROIs) were drawn, and cerebral blood flow
      (CBF), cerebral blood volume (CBV), and mean transit time (MTT) in these ROIs
      were recorded and compared. Volume and geographic distribution of ischemic core
      and penumbra using both deconvolution methods were also recorded and compared.
      RESULTS: MTT and CBF values are affected by the deconvolution method used (p <
      0.05), while CBV values remain unchanged. Optimal thresholds to delineate
      ischemic core and penumbra are different for delay-sensitive (145 % MTT, CBV 2 ml
      * 100 g(-1) * min(-1)) and delay-insensitive deconvolution (135 % MTT, CBV 2 ml *
      100 g(-1) * min(-1) for delay-insensitive deconvolution). When applying these
      different thresholds, however, the predicted ischemic core (p = 0.366) and
      penumbra (p = 0.405) were similar with both methods. CONCLUSION: Both delay
      sensitive and delay-insensitive deconvolution methods are appropriate for PCT
      processing in acute ischemic stroke patients. The predicted ischemic core and
      penumbra are similar with both methods when using different sets of thresholds,
      specific for each deconvolution method.

PMID- 25749852
TI  - Infected cardiac-implantable electronic devices: prevention, diagnosis, and
      treatment.
AB  - Cardiac implantable electronic device (CIED) infection, according to current
      trends, appears to be an increasing problem. It can be indolent and its diagnosis
      challenging. Cardiac implantable electronic device infections are potentially
      lethal, and timely diagnosis and early initiation of correct treatment are of
      highest importance for patient prognosis. For reducing CIED infections, careful
      patient selection, preventative measures, and appropriate choice of device are
      key. The current review presents available data and consensus opinion within the
      field of CIED infection and identifies important current practice points and
      aspects for future development. Strategies for reducing CIED infection should be
      tested in sufficiently powered and well-designed multicentre randomized
      controlled trials. 

PMID- 25749853
TI  - Thrombus trapped in patent foramen ovale.

PMID- 25749854
TI  - Early Cholecystectomy Is Superior to Delayed Cholecystectomy for Acute
      Cholecystitis: a Meta-analysis.
AB  - INTRODUCTION: The timing of laparoscopic cholecystectomy for acute cholecystitis
      remains an issue for debate amongst general surgeons. The aim of this study was
      to compare clinical outcomes between early and delayed cholecystectomy for acute
      cholecystitis. The primary outcome measures included mortality rates,
      complication rates, length of hospital stay and conversion rates to open
      procedures. MATERIALS AND METHODS: A search of electronic databases was performed
      for randomised controlled trials. Fifteen studies were included. RESULTS: Early
      surgery has a decreased risk of wound infections (RR 0.57, 95 % CI 0.35-0.93,
      p=0.01) compared with delayed surgery but no difference in mortality, bile duct
      injuries, bile duct leaks and the risk of conversion to open surgery. Of patients
      in the delayed group, 9.7 % failed initial non-operative management and underwent
      emergency LC. Early surgery had a significantly reduced total hospital stay and
      mean hospital costs compared with delayed surgery. CONCLUSION: Early laparoscopic
      cholecystectomy in acute cholecystitis demonstrated decreased incidence of wound
      infections, a shorter total length of stay and decreased costs with no difference
      in the rates of mortality, bile duct injuries, bile leaks and conversions. These
      results support that early laparoscopic cholecystectomy is the best care and
      should be considered a routine in patients presenting with acute cholecystitis.

PMID- 25749855
TI  - Predictive factors for surgery among patients with pancreatic cysts in the
      absence of high-risk features for malignancy.
AB  - BACKGROUND: Without a reliable biopsy technique for pancreatic cysts, consensus
      based guidelines are used to guide surgical utilization. The primary objective of
      this study was to characterize the proportion of operations performed outside of
      these guidelines. METHODS: A 5-year retrospective review between July 1, 2007,
      and June 30, 2012, was performed of consecutive patients seen at a single
      tertiary medical center for a pancreatic cyst. Manual chart review for relevant
      clinical variables and cyst characteristics was performed. RESULTS: During this
      period, 148 patients underwent surgery, and of these, 23 (16 %) patients had no
      high-risk criteria by the 2006 Sendai criteria. None of these harbored high-grade
      dysplastic or cancerous lesions. A high cyst carcinoembryonic antigen (CEA) level
      (35 %), patient anxiety (26 %), and physician concern (22 %) were explicit
      reasons to proceed to surgery. An elevated cyst CEA level >192 ng/ml was the most
      significant predictor (OR 5.14 (95 % confidence interval (CI) 1.47-18.0) for
      surgery without high-risk criteria. CONCLUSION: A high cyst CEA level was
      significantly associated with the decision to operate outside of consensus-based
      guidelines. The misuse of cyst CEA in the management of pancreatic cysts
      negatively impacts patient anxiety, increases physician uncertainty, and leads to
      surgery with minimal benefit.

PMID- 25749856
TI  - Towards adaptive IMRT sequencing for the MR-linac.
AB  - The MRI linear accelerator (MR-linac) that is currently being installed in the
      University Medical Center Utrecht (Utrecht, The Netherlands), will be able to
      track the patient's target(s) and Organ(s) At Risk during radiation delivery. In
      this paper, we present a treatment planning system for intensity-modulated
      radiotherapy (IMRT). It is capable of Adaptive Radiotherapy and consists of a GPU
      Monte Carlo dose engine, an inverse dose optimization algorithm and a novel
      adaptive sequencing algorithm. The system is able to compensate for patient
      anatomy changes and enables radiation delivery immediately from the first
      calculated segment. IMRT plans meeting all clinical constraints were generated
      for two breast cases, one spinal bone metastasis case, two prostate cases with
      integrated boost regions and one head and neck case. These plans were generated
      by the segment weighted version of our algorithm, in a 0 T environment in order
      to test the feasibility of the new sequencing strategy in current clinical
      conditions, yielding very small differences between the fluence and sequenced
      distributions. All plans went through stringent experimental quality assurance on
      Delta4 and passed all clinical tests currently performed in our institute. A new
      inter-fraction adaptation scheme built on top of this algorithm is also proposed
      that enables convergence to the ideal dose distribution without the need of a
      final segment weight optimization. The first results of this method confirm that
      convergence is achieved within the first fractions of the treatment. These
      features combined will lead to a fully adaptive intra-fraction planning system
      able to take into account patient anatomy updates during treatment.

PMID- 25749857
TI  - Bidirectional transynaptic degeneration after resection of brainstem pilocytic
      astrocytoma.

PMID- 25749858
TI  - How to identify hypertensive patients at high cardiovascular risk? The role of
      echocardiography.
AB  - Scientific authorities recommend that patients with arterial hypertension should
      be managed not only on the basis of blood pressure (BP) levels, but also on the
      assemement of total cardiovascular risk. In particular, evaluation of target
      organ damage (TOD) is of major relevance for identifying hypertensive individuals
      at high cardiovascular risk independently of clinic BP levels. Evidence of
      cardiac and extra-cardiac TOD has been consistently associated with worse
      cardiovascular prognosis. Unfortunately, detection of TOD markedly depends on
      sensitivity of diagnostic tools, at difference from evaluation of risk factors
      and associated diseases, usually reliably provided by accurate clinical
      examination and routine investigation. The purpose of this paper was to provide
      an updated, comprehensive review on the role of echocardiography in identifying
      hypertensive patients apparently uncomplicated, but exposed to a high
      cardiovascular risk due to the presence of subclinical structural and functional
      cardiac alterations of adverse prognostic significance. 

PMID- 25749861
TI  - Emerging roles of protocadherins: from self-avoidance to enhancement of motility.
AB  - Protocadherins are a group of transmembrane proteins belonging to the cadherin
      superfamily that are subgrouped into 'clustered' and 'non-clustered'
      protocadherins. Although cadherin superfamily members are known to regulate
      various forms of cell-cell interactions, including cell-cell adhesion, the
      functions of protocadherins have long been elusive. Recent studies are, however,
      uncovering their unique roles. The clustered protocadherins regulate neuronal
      survival, as well as dendrite self-avoidance. Combinatorial expression of
      clustered protocadherin isoforms creates a great diversity of adhesive
      specificity for cells, and this process is likely to underlie the dendritic self
      avoidance. Non-clustered protocadherins promote cell motility rather than the
      stabilization of cell adhesion, unlike the classic cadherins, and mediate dynamic
      cellular processes, such as growth cone migration. Protocadherin dysfunction in
      humans is implicated in neurological disorders, such as epilepsy and mental
      retardation. This Commentary provides an overview of recent findings regarding
      protocadherin functions, as well as a discussion of the molecular basis
      underlying these functions. 

PMID- 25749860
TI  - Modeling the effective connectivity of the visual network in healthy and
      photosensitive, epileptic baboons.
AB  - The baboon provides a model of photosensitive, generalized epilepsy. This study
      compares cerebral blood flow responses during intermittent light stimulation
      (ILS) between photosensitive (PS) and healthy control (CTL) baboons using H 2
      (15) O-PET. We examined effective connectivity associated with visual stimulation
      in both groups using structural equation modeling (SEM). Eight PS and six CTL
      baboons, matched for age, gender and weight, were classified on the basis of
      scalp EEG findings performed during the neuroimaging studies. Five H 2 (15) O-PET
      studies were acquired alternating between resting and activation (ILS at 25 Hz)
      scans. PET images were acquired in 3D mode and co-registered with MRI. SEM
      demonstrated differences in neural connectivity between PS and CTL groups during
      ILS that were not previously identified using traditional activation analyses.
      First-level pathways consisted of similar posterior-to-anterior projections in
      both groups. While second-level pathways were mainly lateralized to the left
      hemisphere in the CTL group, they consisted of bilateral anterior-to-posterior
      projections in the PS baboons. Third- and fourth-level pathways were only evident
      in PS baboons. This is the first functional neuroimaging study used to model the
      photoparoxysmal response (PPR) using a primate model of photosensitive,
      generalized epilepsy. Evidence of increased interhemispheric connectivity and
      bidirectional feedback loops in the PS baboons represents electrophysiological
      synchronization associated with the generation of epileptic discharges. PS
      baboons demonstrated decreased model stability compared to controls, which may be
      attributed to greater variability in the driving response or PPRs, or to the
      influence of regions not included in the model.

PMID- 25749859
TI  - Axotomy of tributaries of the pelvic and pudendal nerves induces changes in the
      neurochemistry of mouse dorsal root ganglion neurons and the spinal cord.
AB  - Using immunohistochemical techniques, we characterized changes in the expression
      of several neurochemical markers in lumbar 4-sacral 2 (L4-S2) dorsal root
      ganglion (DRG) neuron profiles (NPs) and the spinal cord of BALB/c mice after
      axotomy of the L6 and S1 spinal nerves, major tributaries of the pelvic
      (targeting pelvic visceral organs) and pudendal (targeting perineum and
      genitalia) nerves. Sham animals were included. Expression of cyclic AMP-dependent
      transcription factor 3 (ATF3), calcitonin gene-related peptide (CGRP), transient
      receptor potential cation channel subfamily V, member 1 (TRPV1), tyrosine
      hydroxylase (TH) and vesicular glutamate transporters (VGLUT) types 1 and -2 was
      analysed seven days after injury. L6-S1 axotomy induced dramatic de novo
      expression of ATF3 in many L6-S1 DRG NPs, and parallel significant
      downregulations in the percentage of CGRP-, TRPV1-, TH- and VGLUT2-immunoreactive
      (IR) DRG NPs, as compared to their expression in uninjured DRGs (contralateral L6
      S1-AXO; sham mice); VGLUT1 expression remained unaltered. Sham L6-S1 DRGs only
      showed a small ipsilateral increase in ATF3-IR NPs (other markers were
      unchanged). L6-S1-AXO induced de novo expression of ATF3 in several lumbosacral
      spinal cord motoneurons and parasympathetic preganglionic neurons; in sham mice
      the effect was limited to a few motoneurons. Finally, a moderate decrease in CGRP
      and TRPV1-like-immunoreactivities was observed in the ipsilateral superficial
      dorsal horn neuropil. In conclusion, injury of a mixed visceral/non-visceral
      nerve leads to considerable neurochemical alterations in DRGs matched, to some
      extent, in the spinal cord. Changes in these and potentially other nociception
      related molecules could contribute to pain due to injury of nerves in the
      abdominopelvic cavity.

PMID- 25749862
TI  - The dual structural roles of the membrane distal region of the alpha-integrin
      cytoplasmic tail during integrin inside-out activation.
AB  - Studies on the mechanism of integrin inside-out activation have been focused on
      the role of beta-integrin cytoplasmic tails, which are relatively conserved and
      bear binding sites for the intracellular activators including talin and kindlin.
      Cytoplasmic tails for alpha-integrins share a conserved GFFKR motif at the
      membrane-proximal region and this forms a specific interface with the beta
      integrin membrane-proximal region to keep the integrin inactive. The alpha
      integrin membrane-distal regions, after the GFFKR motif, are diverse both in
      length and sequence and their roles in integrin activation have not been well
      defined. In this study, we report that the alpha-integrin cytoplasmic membrane
      distal region contributes to maintaining integrin in the resting state and to
      integrin inside-out activation. Complete deletion of the alpha-integrin membrane
      distal region diminished talin- and kindlin-mediated integrin ligand binding and
      conformational change. A proper length and suitable amino acids in alpha-integrin
      membrane-distal region was found to be important for integrin inside-out
      activation. Our data establish an essential role for the alpha-integrin
      cytoplasmic membrane-distal region in integrin activation and provide new
      insights into how talin and kindlin induce the high-affinity integrin
      conformation that is required for fully functional integrins. 

PMID- 25749864
TI  - Co-expression of VGLUT1 and VGAT sustains glutamate and GABA co-release and is
      regulated by activity in cortical neurons.
AB  - In adult neocortex, VGLUT1 (also known as SLC17A7), the main glutamate vesicular
      transporter, and VGAT (also known as SLC32A1), the gamma-aminobutyric acid (GABA)
      vesicular transporter, are co-expressed in a subset of axon terminals forming
      both symmetric and asymmetric synapses, where they are sorted into the same
      vesicles. However, the functional consequence of this colocalization in cortical
      neurons has not been clarified. Here, we tested the hypothesis that cortical axon
      terminals co-expressing VGLUT1 and VGAT can evoke simultaneously monosynaptic
      glutamate and GABA responses, and investigated whether the amount of terminals co
      expressing VGLUT1 and VGAT is affected by perturbations of excitation-inhibition
      balance. In rat primary cortical neurons, we found that a proportion of synaptic
      and autaptic responses were indeed sensitive to consecutive application of
      selective glutamate and GABAA receptor blockers. These 'mixed' synapses exhibited
      paired-pulse depression. Notably, reducing the activity of the neuronal network
      by treatment with glutamate receptor antagonists decreased the amount of 'mixed'
      synapses, whereas reducing spontaneous inhibition by treatment with bicuculline
      increased them. These synapses might contribute to homeostatic regulation of
      excitation-inhibition balance. 

PMID- 25749863
TI  - The adipocyte clock controls brown adipogenesis through the TGF-beta and BMP
      signaling pathways.
AB  - The molecular clock is intimately linked to metabolic regulation, and brown
      adipose tissue plays a key role in energy homeostasis. However, whether the cell
      intrinsic clock machinery participates in brown adipocyte development is unknown.
      Here, we show that Bmal1 (also known as ARNTL), the essential clock transcription
      activator, inhibits brown adipogenesis to adversely affect brown fat formation
      and thermogenic capacity. Global ablation of Bmal1 in mice increases brown fat
      mass and cold tolerance, and adipocyte-selective inactivation of Bmal1
      recapitulates these effects and demonstrates its cell-autonomous role in brown
      adipocyte formation. Further loss- and gain-of-function studies in mesenchymal
      precursors and committed brown progenitors reveal that Bmal1 inhibits brown
      adipocyte lineage commitment and terminal differentiation. Mechanistically, Bmal1
      inhibits brown adipogenesis through direct transcriptional control of key
      components of the TGF-beta pathway together with reciprocally altered BMP
      signaling; activation of TGF-beta or blockade of BMP pathways suppresses enhanced
      differentiation in Bmal1-deficient brown adipocytes. Collectively, our study
      demonstrates a novel temporal regulatory mechanism in fine-tuning brown adipocyte
      lineage progression to affect brown fat formation and thermogenic regulation,
      which could be targeted therapeutically to combat obesity. 

PMID- 25749865
TI  - CORR Insights((r)): Are Allogeneic Blood Transfusions Associated With Decreased
      Survival After Surgery for Long-bone Metastatic Fractures?

PMID- 25749866
TI  - CORR Insights((r)): development of a mouse model of ischemic osteonecrosis.

PMID- 25749867
TI  - Clinical pharmacokinetics of the anti-interleukin-20 monoclonal antibody NNC0109
      0012 in healthy volunteers and patients with psoriasis or rheumatoid arthritis.
AB  - INTRODUCTION: NNC0109-0012, a novel human monoclonal antibody that binds to and
      neutralizes the activity of interleukin-20, was investigated as a potential
      treatment for inflammatory diseases. Pharmacokinetic (PK) modeling was performed
      using data from four completed clinical phase 1/2 trials to better understand the
      clinical PK of NNC0109-0012. METHODS: The populations included were patients with
      rheumatoid arthritis (RA), chronic plaque psoriasis, and healthy volunteers.
      NNC0109-0012 was administered subcutaneously at various dose levels (0.01-3
      mg/kg) as single dose, once weekly, or multiple doses every second week for up to
      12 doses. Noncompartmental methods were used to describe the PK parameters.
      Population PK was analyzed using nonlinear mixed-effects modeling, with body
      weight as the main covariate and gender, age, and population as additional
      covariates. RESULTS: Across studies (N = 116), mean age and body weight ranged
      from 38 to 58 years and 72 to 96 kg, respectively. NNC0109-0012 displays linear
      PK. Time to maximum plasma concentration occurred at approximately 1 week, and
      the terminal half-life was approximately 3 weeks. Clearance and volume of
      distribution increased proportionally to body weight. No difference in clearance
      or volume of distribution was observed between gender or different age groups;
      however, clearance was slightly lower in healthy volunteers than in patients with
      RA. CONCLUSION: The PK profile of NNC0109-0012 is similar to other monoclonal
      antibodies directed against soluble targets.

PMID- 25749868
TI  - Statin-induced decrease in ATP-binding cassette transporter A1 expression via
      microRNA33 induction may counteract cholesterol efflux to high-density
      lipoprotein.
AB  - PURPOSE: Cholesterol efflux from macrophages to HDL, measured in vitro, is
      augmented by treatment with agents which raise HDL cholesterol. In vitro,
      cholesterol depletion by statins is known to trigger a positive feedback on the
      cholesterol synthetic pathway via sterol regulatory element-binding protein
      (SREBP) transcription and changes in expression of SREBP regulated genes
      including microRNA33 (miR33) which is co-transcribed with SREBP and down
      regulates ABCA1 and ABCG1 expression. METHODS: We investigated whether miR33 up
      regulation, associated with SREBP increased transcription by statins, reduces
      macrophage ATP-binding cassette (ABC) transporter expression, thereby decreasing
      HDL-mediated cholesterol efflux at the tissue level. RESULTS: In human macrophage
      THP-1 cells cholesterol-loaded with acetylated LDL, incubation with 1 MUM
      atorvastatin increased miR33 by 33 % (P < 0.05), and decreased ABCA1 messenger
      RNA (mRNA) and ABCG1 mRNA by 47 % (P < 0.05) and 27 % (NS), respectively. In
      J774A.1 mouse macrophage, labelled with 3H-cholesterol, ABCA1 mRNA and ABCA1
      mediated cholesterol efflux were decreased by 1 MUM statin: simvastatin >
      pitavastatin > atorvastatin > rosuvastatin > pravastatin. HDL incubated with
      rhCETP and dalcetrapib increased ABCA1-mediated cholesterol efflux. However,
      incremental simvastatin concentrations decreased cholesterol efflux to HDL
      treated with rhCETP and dalcetrapib. When HDL was incubated with rhCETP, addition
      of dalcetrapib augmented ABCA1-mediated cholesterol efflux from J774A.1
      macrophages. However, simvastatin >=1 MUM virtually eliminated any HDL-ABCA1
      mediated cholesterol efflux and any augmentation of that process by dalcetrapib.
      CONCLUSIONS: In vitro, statins increase miR33 expression, and decrease ABCA1
      expression and cholesterol efflux from peripheral tissues; this may counteract
      the potential benefit of agents that raise HDL and apolipoprotein A-I in statin
      treated patients.

PMID- 25749869
TI  - HIV patients have impaired diastolic function that is not aggravated by anti
      retroviral treatment.
AB  - PURPOSE: Recent studies have shown that HIV infection is independently associated
      with heart failure. Diastolic dysfunction (DD) is frequent in HIV patients, but
      it is unclear whether this is an effect of the HIV infection itself or of the
      anti-retroviral therapy (ART). Our aim was to compare diastolic function in HIV
      treatment-naive, HIV-ART patients and controls. METHODS: We prospectively
      enrolled 206 consecutive patients with HIV-1 infection and 30 controls, selected
      by frequency matching for age and sex. HIV patients were divided in two
      subgroups: ART-naive (n = 88) and ART (n = 118). Diastolic function was assessed
      and graded by echocardiography, according to modern consensus criteria and using
      tissue Doppler analysis. RESULTS: Compared to controls, ART-naive patients had
      lower E' velocities (E' septal: 10.2 +/- 2.4 vs 11.9 +/- 2.6 cm/s, p = 0.02),
      higher E/E' ratio (7.8 +/- 1.9 vs 6.9 +/- 1.6,p = 0.02) and higher prevalence of
      DD (19 % vs 3.3 %,p = 0.05). HIV patients under ART also had worse diastolic
      function compared to controls (E' septal: 10.3 +/- 2.5 cm/s;p < 0.01; E/E'ratio:
      8.0 +/- 2.0,p < 0.01; DD prevalence: 23 %;p = 0.01), but no significant
      differences were found between ART-naive and ART HIV subgroups. In multivariable
      logistic regression analysis, age and body mass index were the only independent
      predictors of reduced diastolic reserve in HIV patients. Regarding systolic
      function, there were no significant differences in ejection fraction or S'
      velocities between controls and HIV subgroups. CONCLUSIONS: HIV treatment-naive
      patients have reduced diastolic reserve that is not worsened by ART. These data
      reinforce the association of diastolic dysfunction with the HIV infection itself
      and not with the anti-retroviral therapy.

PMID- 25749870
TI  - Erratum to: Correlation of chemical shifts predicted by molecular dynamics
      simulations for partially disordered proteins.

PMID- 25749871
TI  - Simultaneous acquisition of 2D and 3D solid-state NMR experiments for sequential
      assignment of oriented membrane protein samples.
AB  - We present a new method called DAISY (Dual Acquisition orIented ssNMR
      spectroScopY) for the simultaneous acquisition of 2D and 3D oriented solid-state
      NMR experiments for membrane proteins reconstituted in mechanically or
      magnetically aligned lipid bilayers. DAISY utilizes dual acquisition of sine and
      cosine dipolar or chemical shift coherences and long living (15)N longitudinal
      polarization to obtain two multi-dimensional spectra, simultaneously. In these
      new experiments, the first acquisition gives the polarization inversion spin
      exchange at the magic angle (PISEMA) or heteronuclear correlation (HETCOR)
      spectra, the second acquisition gives PISEMA-mixing or HETCOR-mixing spectra,
      where the mixing element enables inter-residue correlations through (15)N-(15)N
      homonuclear polarization transfer. The analysis of the two 2D spectra (first and
      second acquisitions) enables one to distinguish (15)N-(15)N inter-residue
      correlations for sequential assignment of membrane proteins. DAISY can be
      implemented in 3D experiments that include the polarization inversion spin
      exchange at magic angle via I spin coherence (PISEMAI) sequence, as we show for
      the simultaneous acquisition of 3D PISEMAI-HETCOR and 3D PISEMAI-HETCOR-mixing
      experiments.

PMID- 25749872
TI  - Extending the eNOE data set of large proteins by evaluation of NOEs with
      unresolved diagonals.
AB  - The representation of a protein's spatial sampling at atomic resolution is
      fundamental for understanding its function. NMR has been established as the best
      suited technique toward this goal for small proteins. However, the accessible
      information content rapidly deteriorates with increasing protein size. We have
      recently demonstrated that for small proteins distance restraints with an
      accuracy smaller than 0.1 A can be obtained by replacing traditional semi
      quantitative Nuclear Overhauser Effects (NOEs) with exact NOEs (eNOE). The high
      quality of the data allowed us to calculate structural ensembles of the small
      model protein GB3 consisting of multiple rather than a single state. The analysis
      has been limited to small proteins because NOEs of spins with unresolved diagonal
      peaks cannot be used. Here we propose a simple approach to translate such NOEs
      into correct upper distance restraints, which opens access to larger
      biomolecules. We demonstrate that for 16 kDa cyclophilin A the collection of such
      restraints extends the original 1254 eNOEs to 3471.

PMID- 25749873
TI  - Perceptions of usage and unintended consequences of provision of ready-to-use
      therapeutic food for management of severe acute child malnutrition. A qualitative
      study in Southern Ethiopia.
AB  - BACKGROUND: Severe acute child malnutrition (SAM) is associated with high risk of
      mortality. To increase programme effectiveness in management of SAM, community
      based management of acute malnutrition (CMAM) programme that treats SAM using
      ready-to-use-therapeutic foods (RUTF) has been scaled-up and integrated into
      existing government health systems. The study aimed to examine caregivers' and
      health workers perceptions of usages of RUTF in a chronically food insecure area
      in South Ethiopia. METHODS: This qualitative study recorded, transcribed and
      translated focus group discussions and individual interviews with caregivers of
      SAM children and community health workers (CHWs). Data were complemented with
      field notes before qualitative content analysis was applied. RESULTS: RUTF was
      perceived and used as an effective treatment of SAM; however, caregivers also see
      it as food to be shared and when necessary a commodity to be sold for collective
      benefits for the household. Caregivers expected prolonged provision of RUTF to
      contribute to household resources, while the programme guidelines prescribed RUTF
      as a short-term treatment to an acute condition in a child. To get prolonged
      access to RUTF caregivers altered the identities of SAM children and sought
      multiple admissions to CMAM programme at different health posts that lead to
      various control measures by the CHWs. CONCLUSION: Even though health workers
      provide RUTF as a treatment for SAM children, their caregivers use it also for
      meeting broader food and economic needs of the household endangering the
      effectiveness of CMAM programme. In chronically food insecure contexts,
      interventions that also address economic and food needs of entire household are
      essential to ensure successful treatment of SAM children. This may need a shift
      to view SAM as a symptom of broader problems affecting a family rather than a
      disease in an individual child.

PMID- 25749874
TI  - Prevalence and Correlates of Self-Reported ADD/ADHD in a Large National Sample of
      Canadian Adults.
AB  - OBJECTIVE: The objective of this study was to examine the prevalence and
      correlates of self-reported attention deficit disorder (ADD)/ADHD in Canadian
      adults. METHOD: Prevalence of self-reported ADD/ADHD was examined in a large
      national sample of Canadians ( n = 16,957). Demographic variables, lifetime, and
      current psychiatric comorbidities were then compared in a group of adults with
      self-reported ADD/ADHD ( n = 488) and an age- and gender-matched control group (
      n = 488). RESULTS: The prevalence of self-reported ADD/ADHD was 2.9%.
      Significantly higher lifetime and current prevalence rates of major depressive
      disorder, bipolar I and II disorders, generalized anxiety disorder, and substance
      use disorders were observed in the ADD/ADHD group compared with the control
      group. Within the ADD/ADHD group, lifetime and 12-month prevalence rates of major
      depressive disorder and generalized anxiety disorder were significantly higher in
      women, whereas lifetime and current rates of some substance use disorders were
      significantly higher in men. CONCLUSION: In a national sample of Canadian adults,
      self-reported ADD/ADHD was associated with significant psychiatric comorbidity.
      Gender differences were also noted.

PMID- 25749875
TI  - The role of checkpoints in the treatment of GBM.
AB  - Targeted immunotherapy is founded on the principle that augmentation of effector
      T cell activity in the tumor microenvironment can translate to tumor regression.
      Targeted checkpoint inhibitors in the form of agonist or antagonist monoclonal
      antibodies have come to the fore as a promising strategy to activate systemic
      immunity and enhance T cell activity by blocking negative signals, enhancing
      positive signals, or altering the cytokine milieu. This review will examine
      several immune checkpoints and checkpoint modulators that play a role in cancer
      pathogenesis, with an emphasis on malignant gliomas. 

PMID- 25749876
TI  - Wnt5a/Ror2 mediates temporomandibular joint subchondral bone remodeling.
AB  - Increased subchondral trabecular bone turnover due to imbalanced bone-resorbing
      and bone-forming activities is a hallmark of osteoarthritis (OA). Wnt5a/Ror2
      signaling, which can derive from bone marrow stromal cells (BMSCs), takes a role
      in modulating osteoblast and osteoclast formation. We showed previously that
      experimentally unilateral anterior crossbites (UACs) elicited OA-like lesions in
      mice temporomandibular joints (TMJs), displaying as subchondral trabecular bone
      loss. Herein, we tested the role of BMSC-derived Wnt5a/Ror2 signaling in
      regulating osteoclast precursor migration and differentiation in this process.
      The data confirmed the decreased bone mass, increased tartrate-resistant acid
      phosphatase (TRAP)-positive cell number, and enhanced osteoclast activity in TMJ
      subchondral trabecular bone of UAC-treated rats. Interestingly, the osteoblast
      activity in the tissue of TMJ subchondral trabecular bone of these UAC-treated
      rats was also enhanced, displaying as upregulated expressions of osteoblast
      markers and increased proliferation, migration, and differentiation capabilities
      of the locally isolated BMSCs. These BMSCs showed an increased CXCL12 protein
      expression level and upregulated messenger RNA expressions of Rankl, Wnt5a, and
      Ror2. Ex vivo data showed that their capacities of inducing migration and
      differentiation of osteoclast precursors were enhanced, and these enhanced
      capabilities were restrained after blocking their Ror2 signaling using small
      interfering RNA (siRNA) assays. Reducing Ror2 expression in the BMSC cell line by
      siRNA or blocking the downstream signalings with specific inhibitors also
      demonstrated a suppression of the capacity of the BMSC cell line to promote Wnt5a
      dependent migration (including SP600125 and cyclosporine A) and differentiation
      (cyclosporine A only) of osteoclast precursors. These findings support the idea
      that Wnt5a/Ror2 signaling in TMJ subchondral BMSCs enhanced by UAC promoted BMSCs
      to increase Cxcl12 and Rankl expression, in which JNK and/or Ca(2+)/NFAT pathways
      were involved and therefore were engaged in enhancing the migration and
      differentiation of osteoclast precursors, leading to increased osteoclast
      activity and an overall TMJ subchondral trabecular bone loss in the UAC-treated
      rats. 

PMID- 25749877
TI  - Analysis of the tortuosity of the internal carotid artery in the cavernous sinus.
AB  - BACKGROUND: The morphology of the internal carotid artery at the skull base is
      important in radiologic interpretation, surgery, and more recently, endovascular
      interventional and diagnostic procedures. Therefore, a thorough knowledge of the
      shape of the carotid siphon can be important in the clinical realm. METHODS: In
      this study, we evaluated the shape of the carotid siphon from a lateral
      perspective on cerebral angiography. These shapes were then correlated to the
      Lang and Reiter classification. RESULTS: Types A, B, and C were distributed as
      follows: type A 12 (30%), B 16 (40%), 12 (30%). There was no significant
      difference (p > 0.05) in patient ages between the three types (type A 54.6 +/-
      14.2 years, type B 55.1 +/- 14.9 years, and type C 52.7 +/- 16.9 years).
      Normalized for gender disproportion, there was no significant gender predominance
      for any type (type A female:male = 1.4:1; type B female:male = 1.1:1; type C
      female:male = 0.7:1). CONCLUSIONS: Such a classification scheme with additional
      application in another group might be of use to future studies aimed at the
      morphology of the cavernous part of the internal carotid artery.

PMID- 25749878
TI  - Dietary soy isoflavones increase metastasis to lungs in an experimental model of
      breast cancer with bone micro-tumors.
AB  - Bone is one of the most common sites for metastasis in breast cancer (BC). Micro
      metastasis in bone marrow was detected in 30% of patients with stage I, II, or
      III BC at primary surgery and is a strong indicator of poor prognosis. The role
      dietary soy isoflavones play in BC with bone micro-metastasis is unclear. In this
      study, we examined the effects of genistein, daidzein, (-)-equol or a mixture of
      soy isoflavones on BC with bone micro-metastasis using an experimental model of
      murine mammary cancer 4T1 cells engineered with luciferase. A small number (1000)
      of 4T1 cells were injected into the tibia of female Balb/c mice to establish
      micro-tumors in bone. Soy isoflavones were supplemented in the AIN-93G diet at
      750 mg/kg and were provided to mice from 3 weeks before to 3 weeks after cell
      injection. Bioluminescent imaging was conducted on day 2 (D2), D6, D8, D16 and
      D20 post cell injection and the results indicated dietary soy isoflavones
      enhanced the growth of bone micro-tumors on D8. Furthermore, dietary soy
      isoflavones stimulated metastatic tumor formation in lungs and increased Ki-67
      protein expression in these metastasized tumors. In vitro, soy isoflavones (<10
      uM) had limited effects on the growth, motility or invasion of 4T1 cells. Thus,
      the in vivo stimulatory effect could be likely due to systemic effects between
      the host, 4T1 tumors and soy isoflavones. In conclusion, soy isoflavones
      stimulate BC with bone micro-metastasis in mice and further investigations are
      needed regarding their consumption by BC survivors.

PMID- 25749879
TI  - Dormancy and growth of metastatic breast cancer cells in a bone-like
      microenvironment.
AB  - Breast cancer can reoccur, often as bone metastasis, many years if not decades
      after the primary tumor has been treated. The factors that stimulate dormant
      metastases to grow are not known, but bone metastases are often associated with
      skeletal trauma. We used a dormancy model of MDA-MB-231BRMS1, a metastasis
      suppressed human breast cancer cell line, co-cultured with MC3T3-E1 osteoblasts
      in a long term, three dimensional culture system to test the hypothesis that bone
      remodeling cytokines could stimulate dormant cells to grow. The cancer cells
      attached to the matrix produced by MC3T3-E1 osteoblasts but grew slowly or not at
      all until the addition of bone remodeling cytokines, TNFalpha and IL-beta.
      Stimulation of cell proliferation by these cytokines was suppressed with
      indomethacin, an inhibitor of cyclooxygenase and of prostaglandin production, or
      a prostaglandin E2 (PGE2) receptor antagonist. Addition of PGE2 directly to the
      cultures also stimulated cell proliferation. MCF-7, non-metastatic breast cancer
      cells, remained dormant when co-cultured with normal human osteoblast and
      fibroblast growth factor. Similar to the MDA-MB-231BRMS1 cells, MCF-7
      proliferation increased in response to TNFalpha and IL-beta. These findings
      suggest that changes in the bone microenvironment due to inflammatory cytokines
      associated with bone repair or excess turnover may trigger the occurrence of
      latent bone metastasis. 

PMID- 25749880
TI  - Simulating Strategies for Improving Control of Hypertension Among Patients with
      Usual Source of Care in the United States: The Blood Pressure Control Model.
AB  - BACKGROUND: Only half of hypertensive adults achieve blood pressure (BP) control
      in the United States, and it is unclear how BP control rates may be improved most
      effectively and efficiently at the population level. OBJECTIVE: We sought to
      compare the potential effects of system-wide isolated improvements in medication
      adherence, visit frequency, and higher physician prescription rate on achieving
      BP control at 52 weeks. DESIGN: We developed a Markov microsimulation model of
      patient-level, physician-level, and system-level processes involved in
      controlling hypertension with medications. The model is informed by data from
      national surveys, cohort studies and trials, and was validated against two
      multicenter clinical trials (ALLHAT and VALUE). SUBJECTS: We studied a simulated,
      nationally representative cohort of patients with diagnosed but uncontrolled
      hypertension with a usual source of care. INTERVENTIONS: We simulated a base case
      and improvements of 10 and 50%, and an ideal scenario for three modifiable
      parameters: visit frequency, treatment intensification, and medication adherence.
      Ideal scenarios were defined as 100% for treatment intensification and adherence,
      and return visits occurring within 4 weeks of an elevated office systolic BP.
      MAIN OUTCOME: BP control at 52 weeks of follow-up was examined. RESULTS: Among
      25,000 hypothetical adult patients with uncontrolled hypertension (systolic BP >=
      140 mmHg), only 18% achieved BP control after 52 weeks using base-case
      assumptions. With 10/50%/idealized enhancements in each isolated parameter,
      enhanced treatment intensification achieved the greatest BP control (19/23/71%),
      compared with enhanced visit frequency (19/21/35%) and medication adherence
      (19/23/26%). When all three processes were idealized, the model predicted a BP
      control rate of 95% at 52 weeks. CONCLUSION: Substantial improvements in BP
      control can only be achieved through major improvements in processes of care.
      Healthcare systems may achieve greater success by increasing the frequency of
      clinical encounters and improving physicians' prescribing behavior than by
      attempting to improve patient adherence to medications.

PMID- 25749881
TI  - Hospital Evaluations by Social Media: A Comparative Analysis of Facebook Ratings
      among Performance Outliers.
AB  - BACKGROUND: An increasing number of hospitals and health systems utilize social
      media to allow users to provide feedback and ratings. The correlation between
      ratings on social media and more conventional hospital quality metrics remains
      largely unclear, raising concern that healthcare consumers may make decisions on
      inaccurate or inappropriate information regarding quality. OBJECTIVES: The
      purpose of this study was to examine the extent to which hospitals utilize social
      media and whether user-generated metrics on Facebook((r)) correlate with a
      Hospital Compare((r)) metric, specifically 30-day all cause unplanned hospital
      readmission rates. DESIGN AND PARTICIPANTS: This was a retrospective cross
      sectional study conducted among all U.S. hospitals performing outside the
      confidence interval for the national average on 30-day hospital readmission rates
      as reported on Hospital Compare. Participants were 315 hospitals performing
      better than U.S. national rate on 30-day readmissions and 364 hospitals
      performing worse than the U.S. national rate. MAIN MEASURES: The study analyzed
      ratings of hospitals on Facebook's five-star rating scale, 30-day readmission
      rates, and hospital characteristics including beds, teaching status, urban vs.
      rural location, and ownership type. KEY RESULTS: Hospitals performing better than
      the national average on 30-day readmissions were more likely to use Facebook than
      lower-performing hospitals (93.3 % vs. 83.5 %; p < 0.01). The average rating for
      hospitals with low readmission rates (4.15 +/- 0.31) was higher than that for
      hospitals with higher readmission rates (4.05 +/- 0.41, p < 0.01). Major teaching
      hospitals were 14.3 times more likely to be in the high readmission rate group. A
      one-star increase in Facebook rating was associated with increased odds of the
      hospital belonging to the low readmission rate group by a factor of 5.0 (CI: 2.6
      10.3, p <  0.01), when controlling for hospital characteristics and Facebook
      related variables. CONCLUSIONS: Hospitals with lower rates of 30-day hospital
      wide unplanned readmissions have higher ratings on Facebook than hospitals with
      higher readmission rates. These findings add strength to the concept that
      aggregate measures of patient satisfaction on social media correlate with more
      traditionally accepted measures of hospital quality.

PMID- 25749883
TI  - Capsule commentary on Goetz et al., The effect of charge display on cost of care
      and physician practice behaviors: a systematic review.

PMID- 25749882
TI  - Yelp for Prescribers: A Quasi-Experimental Study of Providing Antibiotic Cost
      Data and Prescription of High-Cost Antibiotics in an Academic and Tertiary Care
      Hospital.
AB  - BACKGROUND: Physicians frequently prescribe antibiotics to inpatients without
      knowledge of medication cost. It is not well understood whether providing cost
      data would change prescribing behavior. OBJECTIVE: To evaluate the association
      between providing cost data alongside culture and antibiotic susceptibility
      results and prescribing of high-cost antibiotics. DESIGN: Quasi-experimental pre
      post analysis. PARTICIPANTS: Inpatients diagnosed with bacteremia or urinary
      tract infection in two tertiary care hospitals. INTERVENTION: Cost category data
      for each antibiotic ($, $$, $$$, or $$) were added to culture and susceptibility
      testing results available to physicians. MAIN MEASURES: Average cost category of
      antibiotics prescribed to patients after the receipt of susceptibility testing
      results. KEY RESULTS: There was a significant decrease in the average cost
      category of antibiotics per patient after the intervention (pre-intervention =
      1.9 $ vs. post-intervention = 1.7 $, where 1.5 $ would mean that the average
      number of dollar signs for antibiotics prescribed was between $ and $$, p =
      0.002). After adjusting for age, insurance type, and prior length of stay, the
      odds ratio (OR) of a patient's average antibiotic being higher cost vs. lower
      cost after the intervention compared to before the intervention was 0.74 [95%
      confidence interval (CI) 0.56, 0.98]. The intervention was associated with a
      31.3% reduction in the average cost per unit of antibiotics prescribed (p <
      0.001). CONCLUSIONS: Providing physicians with cost feedback alongside
      susceptibility testing data was associated with a significant decrease in
      prescription of high-cost antibiotics. This intervention is intuitive, low cost,
      and may shift providers toward lower cost medications when equally acceptable
      options are available.

PMID- 25749884
TI  - Epidemics avoidable and unavoidable.

PMID- 25749886
TI  - Determination of reliable force platform parameters and number of trial to
      evaluate sit-to-stand movement.
AB  - BACKGROUND: Sit-to-stand (STS) movement is useful for evaluating lower limb
      muscle function, especially from force platforms. Nevertheless, due to a lack of
      standardization of the STS movement (e.g., position, subject's instructions,
      etc.), it is difficult to compare results obtained in previous studies. AIMS: The
      aim of the present study was to determine the most relevant condition,
      parameters, and number of trial to perform STS movements. METHODS: In this study,
      STS mechanical (maximal and mean force, impulse) and temporal parameters were
      measured in the vertical, medio-lateral and antero-posterior axes using a force
      platform. Five STS conditions (i.e., with or without armrests, variation of the
      height of the chair and the movement speed) were analyzed to evaluate
      repeatability of different standardized procedures. RESULTS: Most of the
      mechanical and temporal parameters were influenced by the STS condition (p <
      0.05). Regarding vertical axis, results showed a strong to perfect repeatability
      for all parameters (0.72 < ICC < 0.9) for only one condition: STS performed as
      rapidly as possible with a 90 degrees  knee angle when seated, without using
      armrests. Regardless conditions of performance, our results also showed that the
      most repeatable parameters were mean and peak force in medio-lateral axis, and
      the impulse measured in the three directions. Three trials should be performed to
      reach high repeatability. CONCLUSION: Our results suggest that the fast
      condition, with a 90 degrees  knee joint angle, with arms crossed over the chest,
      is the most reliable condition to evaluate performance during STS movement.

PMID- 25749885
TI  - Mitochondrial mechanisms of redox cycling agents implicated in Parkinson's
      disease.
AB  - Environmental agents have been implicated in Parkinson's disease (PD) based on
      epidemiological studies and the ability of toxicants to replicate features of PD.
      However, the precise mechanisms by which toxicants induce dopaminergic toxicity
      observed in the idiopathic form of PD remain to be fully understood. The roles of
      ROS and mitochondria are strongly suggested in the mechanisms by which these
      toxicants exert dopaminergic toxicity. There are marked differences and
      similarities shared by the toxicants in increasing steady-state levels of
      mitochondrial ROS. Furthermore, toxicants increase steady-state mitochondrial ROS
      levels by stimulating the production, inhibiting the antioxidant pathways of
      both. This review will focus on the role of mitochondria and ROS in PD associated
      with environmental exposures to redox-based toxicants. 

PMID- 25749887
TI  - Factors associating with shuttle walking test results in community-dwelling
      elderly people.
AB  - BACKGROUND: The shuttle walking test (SWT) is a simple, widely used method for
      assessing endurance performance in the elderly. Despite widespread community use,
      its associated factors are unclear. AIMS: We aim to identify previously undefined
      SWT association factors in community-dwelling elderly people. METHODS: Herein,
      149 healthy elderly Japanese subjects performed the SWT, and were assessed for
      height, weight, smoking history, 10-m walk time, Timed Up and Go (TUG) scores,
      handgrip strength, skeletal mass index (SMI), forced vital capacity (FVC), forced
      expiratory volume in 1 s (FEV1), cardio-ankle vascular index, and ankle brachial
      index. We divided men and women into higher and lower SWT score groups, compared
      between-group parameters, and performed stepwise multivariate logistic regression
      analysis to identify factors independently associated with SWT scores. RESULTS:
      Age, BMI, 10-m walk time, TUG score, SMI, FVC (L; %-predicted), and FEV1 (L; %
      predicted) were significantly different between SWT score groups for men, while
      in women, significant differences were observed in age, TUG score, handgrip
      strength, FVC (L; %-predicted), and FEV1 (L; %-predicted) (p < 0.05). In the
      multivariate logistic regression model, 10-m walk time, and FEV1 showed
      significant associations with SWT results in men; among women, age was the only
      significantly associated factor (p < 0.05). CONCLUSIONS: Results indicate that
      better lung function and shorter walk time independently associate with SWT
      results in community-dwelling men; in women, age is the only association. Our
      findings may offer insight when considering the focus of community exercise
      programs among the elderly.

PMID- 25749888
TI  - Effects of feline hyperthyroidism on kidney function: a review.
AB  - Chronic kidney disease and hyperthyroidism are two commonly diagnosed conditions
      in the geriatric feline population, and are often seen concurrently. Management
      of both diseases is recommended; however, the physiologic implications of both
      diseases must be understood to ensure the most favorable outcome for each
      patient. This report reviews the complex interplay between hyperthyroidism and
      kidney function, as well as the effects of hyperthyroid therapy on kidney
      function. 

PMID- 25749889
TI  - Retrograde intrarenal surgery for the treatment of renal stones: is fluoroscopy
      free technique achievable?
AB  - The aim of this study was to present the safety and efficacy of retrograde
      intrarenal surgery (RIRS) procedures that minimize the intraoperative radiation
      exposure. The totally endoscopy-guided RIRS technique included the following
      steps: (a) preoperative assessment of pelvicaliceal system anatomy and stone
      characteristics, (b) thorough evaluation of the ureters by rigid ureteroscopy,
      (c) a step-wise approach of introducing the ureteral sheath, (d) gathering stones
      in the more accessible renal calyx before fragmenting them, and (e) a modified
      holmium laser technique. The RIRS procedures performed by a single surgeon
      between October 2012 and October 2013 in consecutive patients with renal stones
      were retrospectively reviewed. The mean stone size was 1.4 +/- 0.4 (range 0.8
      2.0) cm. The median operative time was 74.5 min. Fluoroscopy was only used in one
      patient who had a double collecting system with two ureters. The stone-free
      status was achieved in 134 (95.7%) patients one month after surgery. Five (3.6%)
      patients had minor complications, including hematuria and fever. No major
      intraoperative complication was observed. We believe that with appropriate
      preparation, RIRS without fluoroscopic guidance can be safely and efficiently
      performed by experienced urologists in selected patients with renal stones.

PMID- 25749890
TI  - Loss of Glial Cells of the Hippocampus in a Rat Model of Post-traumatic Stress
      Disorder.
AB  - Single prolonged stress (SPS) rats is a rodent model of post traumatic stress
      disorder (PTSD). Abnormal hippocampal morphology and function were found in the
      PTSD patients. Our previous study has shown that SPS induce loss of hippocampal
      neurons. But the effects of SPS on glial cells in the hippocampus have not been
      evaluated. In the present study, wistar male rats were examined at 1, 4, 7, or 14
      days after SPS. The morris water maze were performed to examine hippocampal
      dependent cognition. The neurometabolite and morphological change in the
      hippocampal neurons and glial cells were investigated using in vivo proton
      magnetic resonance spectroscopy and transmission electron microscopy.
      Immunofluorescence histochemistry and western blotting for Glial fibrillary
      acidic protein (GFAP) was used to evaluate change of astrocytes. SPS rats showed
      increased escape latency. The significant reductions in N-acetylaspartate,
      creatine, and choline-containing compounds in the hippocampus of SPS rats were
      found. Moreover, abnormal morphological characteristics in glial cells of the SPS
      group were observed. The number of GFAP-positive cells, intensity of GFAP-ir and
      GFAP-protein within the hippocampus increased after SPS at 1 day, and then
      decreased. The findings suggested that SPS induced loss/impairment of glial cell
      in the hippocampus; also loss of glial cells may due to the astrocytes reduction
      within the hippocampus of SPS rats.

PMID- 25749891
TI  - Glutamate-Dependent BMAL1 Regulation in Cultured Bergmann Glia Cells.
AB  - Glutamate, the major excitatory amino acid, activates a wide variety of signal
      transduction cascades. This neurotransmitter is involved in photic entrainment of
      circadian rhythms, which regulate physiological and behavioral functions. The
      circadian clock in vertebrates is based on a transcription-translation feedback
      loop in which Brain and muscle aryl hydrocarbon receptor nuclear translocator
      (ARNT)-like protein 1 (BMAL1) acts as transcriptional activator of others clock
      genes. This protein is expressed in nearly all suprachiasmatic nucleus neurons,
      as well as in the granular layer of the cerebellum. In this context, we decided
      to investigate the role of glutamate in the molecular mechanisms involved in the
      processes of transcription/translation of BMAL1 protein. To this end, primary
      cultures of chick cerebellar Bergmann glial cells were stimulated with
      glutamatergic ligands and we found that BMAL1 levels increased in a dose- and
      time dependent manner. Additionally, we studied the phosphorylation of serine
      residues in BMAL1 under glutamate stimulation and we were able to detect an
      increase in the phosphorylation of this protein. The increased expression of
      BMAL1 is most probably the result of a stabilization of the protein after it has
      been phosphorylated by the cyclic AMP-dependent protein kinase and/or the
      Ca(2+)/diacylglycerol dependent protein kinase. The present results strongly
      suggest that glutamate participates in regulating BMAL1 in glial cells and that
      these cells might prove to be important in the control of circadian rhythms in
      the cerebellum.

PMID- 25749893
TI  - Probabilistic approach to lysozyme crystal nucleation kinetics.
AB  - Nucleation of lysozyme crystals in quiescent solutions at a regime of progressive
      nucleation is investigated under an optical microscope at conditions of constant
      supersaturation. A method based on the stochastic nature of crystal nucleation
      and using discrete time sampling of small solution volumes for the presence or
      absence of detectable crystals is developed. It allows probabilities for crystal
      detection to be experimentally estimated. One hundred single samplings were used
      for each probability determination for 18 time intervals and six lysozyme
      concentrations. Fitting of a particular probability function to experimentally
      obtained data made possible the direct evaluation of stationary rates for
      lysozyme crystal nucleation, the time for growth of supernuclei to a detectable
      size and probability distribution of nucleation times. Obtained stationary
      nucleation rates were then used for the calculation of other nucleation
      parameters, such as the kinetic nucleation factor, nucleus size, work for nucleus
      formation and effective specific surface energy of the nucleus. The experimental
      method itself is simple and adaptable and can be used for crystal nucleation
      studies of arbitrary soluble substances with known solubility at particular
      solution conditions. 

PMID- 25749892
TI  - Early identification of renal transplant recipients with high risk of
      polyomavirus-associated nephropathy.
AB  - Polyomavirus BK (BKPyV) is ubiquitous among humans. Following primary infection,
      the virus remains latent predominantly in the hosts' uroepithelial cells. Up to
      10 % of renal transplant recipients show a viral reactivation that can lead to
      polyomavirus-associated nephropathy (PyVAN). In the absence of early treatments,
      the risk of graft loss is up to 80 %. Monitoring viral load in urine and plasma
      by real-time PCR after transplantation is the most common diagnostic tool to
      detect viral reactivation. In the present retrospective study, BKPyV-DNA loads in
      urine and plasma by quantitative real-time PCR were associated with clinical
      data, including HLA haplotype, blood parameters and viral genotype, of 40 renal
      transplant recipients at the University Clinics of Cologne. Seventeen out of 329
      patients screened for BKPyV from January 2009 to October 2013 were detected BKPyV
      positive in urine only, whereas in 23 patients the virus became additionally
      detectable in plasma. Among these, ten patients progressed to PyVAN. Overall, the
      present study showed that the detection from the third month onwards after
      transplantation of a first viruric episode with a median viral load of 1 * 10(8)
      copies/mL, followed after few days by a first viremic episode with a median viral
      load of >1 * 10(4) copies/mL, was strongly associated with the development of
      PyVAN. In conclusion, the viral load and the temporal profile of the first
      viruric and viremic episode post-transplantation, in combination with specific
      features of the host immune response, should be considered as relevant clinical
      determinants of the risk of renal transplant recipients to progress to PyVAN.

PMID- 25749894
TI  - Drug overprescription in nursing homes: an empirical evaluation of administrative
      data.
AB  - A widely discussed shortcoming of long-term care in nursing homes for the elderly
      is the inappropriate or suboptimal drug utilization, particularly of psychotropic
      drugs. Using administrative data from the largest sickness fund in Germany, this
      study was designed to estimate the effect of institutionalization on the drug
      intake of the frail elderly. Difference-in-differences propensity score matching
      techniques were used to compare drug prescriptions for the frail elderly who
      entered a nursing home with those who remained in the outpatient care system;
      findings suggest that nursing home residents receive more doses of
      antipsychotics, antidepressants, and analgesics. The potential overprescription
      correlates with estimated drug costs of about ?87 million per year.

PMID- 25749895
TI  - Systematic and Meta-Analytic Review: Triggering Agents of Parental Perception of
      Child's Vulnerability in Instances of Preterm Birth.
AB  - OBJECTIVE: Parental perception of a child vulnerability (PPCV) to illness, not
      justified by medically noticeable symptoms, is a situation well known to medical
      and paramedical staff. It is still disputed whether PPCV is triggered by the
      child's health problems or by parental emotional status. This review is aimed to
      clarify the etiology of PPCV in instances of preterm birth. METHOD: PRISMA
      guidelines were followed. MEDLINE and Scopus indexes were searched. Of the 70
      articles yielded by the search, 14 met the inclusion criteria for the systematic
      review, of which 10 could be included in the meta-analysis. RESULTS: Children's
      physiological factors and parents' psychological factors were both found to
      significantly influence PPCV, in different ways, at different ages of the child.
      CONCLUSION: PPCV etiology appears to mostly depend on parents' psychological
      factors. A better understanding of PPCV etiology could help protect children from
      distorted parental interaction and reduce parental demands for unnecessary
      medical care.

PMID- 25749896
TI  - Relationship Between Child and Maternal Sleep: A Developmental and Cross-Cultural
      Comparison.
AB  - The aim of this study was to assess the relationship between young children's
      sleep and maternal sleep from both a developmental and a cross-cultural
      perspective. Mothers of 10,085 young children completed the Brief Infant/Child
      Sleep Questionnaire and the Pittsburgh Sleep Quality Index. Overall, there were
      significant relationships between maternal and child sleep for bedtime, waketime,
      number of night wakings, and total nighttime sleep time across ages and cultures,
      although these relationships were stronger with younger children than preschool
      aged children. Mothers report that their child's sleep pattern significantly
      impacts their sleep and daytime function, and they do not feel confident in
      managing their child's sleep pattern. Thus, interventions to improve children's
      sleep and develop good sleep habits, especially in early childhood, are likely to
      improve the quality of life of the whole family. 

PMID- 25749897
TI  - P5-2 of rice black-streaked dwarf virus is a non-structural protein targeted to
      chloroplasts.
AB  - The genome segment S5 of rice black-streaked dwarf virus (genus Fijivirus, family
      Reoviridae) is functionally bicistronic in infected plants. It has a conserved
      second ORF (P5-2) partially overlapping the major ORF in a different reading
      frame, but its function remains unknown. P5-2 was detected in infected plants,
      but not in purified viral particles by Western blotting, indicating that it is a
      non-structural protein. In immunoelectron microscopy, polyclonal antibodies
      against P5-2 specifically labelled chloroplasts of infected rice plants. When P5
      2 fused with green fluorescent protein was transiently expressed in leaves of
      Nicotiana benthamiana, fluorescence was also co-localized with chloroplasts.
      Experiments with deletion mutants of P5-2 showed that its N-terminal part was
      responsible for its targeting to chloroplasts. 

PMID- 25749899
TI  - Gross anatomical classification of the courses of the human sublingual artery.
AB  - The purpose of the present study was to classify the courses of the human
      sublingual artery. For this purpose, the arteries supplying the floor of the
      mouth and the tongue were gross anatomically investigated using 101 sides of 53
      cadavers. The courses were divided into three categories: those passing medial or
      lateral to the hyoglossus (categories M and L) and that piercing the mylohyoid
      (category P); they were subdivided into five types. Category M had one type,
      regarded as the usual one, in which the lingual artery took the usual pattern of
      distribution. Categories L and P, in which the sublingual artery arose from the
      facial or submental artery, had the respective two types and were collectively
      regarded as the unusual type. Sixty-one and 36 of the 101 sides were of the usual
      and unusual types, respectively, the latter of which included 17 of category L
      and 19 of category P. The remaining four were variations of the lingual artery
      itself. On examining the types by gender, the usual type was more often found in
      females (75.6%), whereas the unusual type was more often found in males (48.1%).
      Bilateral occurrence of the same type was often found in both the usual type
      (77.4%) and the unusual type (65.0%). Existence of the sublingual artery branch
      significantly increased the thicknesses of the submental arteries. The
      classification proposed here will conceivably contribute to safer dental implant
      surgery and more accurate interpretation of angiographic images of arteries in
      the floor of the mouth.

PMID- 25749901
TI  - Administration of fenugreek seed extract produces better effects in the
      glibenclamide-induced inhibition in hepatic lipid peroxidation: An in vitro
      study.
AB  - OBJECTIVE: To evaluate the comparative effects of fenugreek (Trigonella foenum
      graecum) seed extract (FSE) alone and in combination with an antidiabetic
      conventional medicine, glibenclamide (GLB), on the inhibition of in vitro lipid
      peroxidation (LPO) in liver, the major target organ of a drug. METHODS: LPO was
      induced by ferrous sulphate (FeSo4), hydrogen peroxide (H2O2) and carbon
      tetrachloride (CCl4) and the effects of test seed extract and/or GLB were
      evaluated. RESULTS: While FeSo4, H2O2 and CCl4 markedly enhanced the hepatic LPO,
      simultaneous administration of FSE reduced it in a concentration dependent
      manner. However, when both FSE and GLB were added to the incubation mixture,
      chemically induced hepatic LPO was further inhibited. The test extract also
      exhibited high antioxidative activity in 1,1-diphenyl-2-picrylhydrazyl radical
      and in 2,2'-azinobis, 3-ethylbenzothiazoline-6-sulphonic acid radical scavenging
      assays. CONCLUSION: FSE therapy in moderate concentration along with a
      hypoglycemic drug may prove to be advantageous in ameliorating diabetes mellitus
      and other diseases that are LPO mediated.

PMID- 25749900
TI  - Treatment results and prognostic factors for intracranial nongerminomatous germ
      cell tumors: single institute experience.
AB  - PURPOSE: This study aimed to evaluate the treatment of intracranial
      nongerminomatous germ cell tumors (NGGCT) and to identify the prognostic factors
      for survival. METHODS: Thirty-nine patients with nondisseminated NGGCTs,
      excluding those with pure mature teratomas, were treated between January 1985 and
      December 2010. Twenty-four patients received gross total or partial removal, 11
      had excision biopsies, and 4 had no surgery. Radiotherapy was given
      postoperatively or definitively with a median tumor bed dose of 54 Gy (range 30
      54) with or without craniospinal irradiation. All patients received ten cycles of
      adjuvant chemotherapy, vinblastine, bleomycin, etoposide, and cisplatin after
      radiotherapy, except for one with mixed anaplastic astrocytoma component who
      received oral temozolomide. Survival and prognostic factors were estimated by the
      Kaplan-Meier method and log-rank tests, respectively. RESULTS: After a median
      follow-up of 77.7 months (range 14-336), the 6-year overall survival (OS) and
      progression-free survival (PFS) were 74.4 and 79.5 %, respectively. Inferior PFS
      was associated with lesions in the suprasellar region (p = 0.017), poor
      pathological features (p = 0.048), and with poor image (p < 0.0001) and tumor
      marker (TM) response (p = 0.003) to irradiation. Decreased OS was associated with
      lesions in the suprasellar region (p = 0.026) and with poor image (p < 0.0001)
      and TM response (p = 0.027) to irradiation. Neither the extent of surgery nor the
      radiation field was found to significantly influence survival. CONCLUSIONS: By
      our multimodality approach, patients achieved comparable outcomes. Other than
      poor pathological features, patients with poor responses to radiotherapy are
      prone to early recurrence and inferior survival. These patients should be focused
      for more intensive adjuvant treatment.

PMID- 25749902
TI  - Ginkgo Biloba extract for angina pectoris: a systematic review.
AB  - OBJECTIVE: To evaluate the efficacy and safety of Ginkgo Biloba extract for
      patients with angina pectoris according to the available evidence. METHODS:
      Electronic databases were searched for all of the randomized controlled trials
      (RCTs) of angina pectoris treatments with Ginkgo Biloba extract, either alone or
      combined with routine Western medicine (RWM), and controlled by untreated,
      placebo, Chinese patent medicine, or RWM treatment. The RCTs were retrieved from
      the following electronic databases: PubMed/MEDLINE, ProQuest Health and Medical
      Complete, Springer, Elsevier, and ProQuest Dissertations and Theses, Wanfang
      Data, China National Knowledge Infrastructure (CNKI), VIP database, China Biology
      Medicine (CBM), Chinese Medical Citation Index (CMCI), from the earliest database
      records to December 2012. No language restriction was applied. Study selection,
      data extraction, quality assessment, and data analyses were conducted according
      to the Cochrane standards. RevMan 5.1.0 provided by Cochrane Collaboration The
      data were analysed by using. RESULTS: A total of 23 RCTs (involving 2,529
      patients) were included and the methodological quality was evaluated as generally
      low. Ginkgo Biloba extract with RWM was more effective in angina relief and
      electrocardiogram improvement than RWM alone. Reported adverse events included
      epigastric discomfort, nausea, gastrointestinal reaction, and bitter taste.
      CONCLUSIONS: Ginkgo Biloba extract may have beneficial effects on patients with
      angina pectoris, although the low quality of existing trials makes it difficult
      to draw a satisfactory conclusion. More rigorous, high quality clinical trials
      are needed to provide conclusive evidence.

PMID- 25749903
TI  - Clinical characteristics of abnormal savda syndrome type in human
      immunodeficiency virus infection and acquired immune deficiency syndrome
      patients: A cross-sectional investigation in Xinjiang, China.
AB  - OBJECTIVE: To investigate the distribution of abnormal hilit syndromes in
      traditional Uighur medicine (TUM) among human immunodeficiency virus infection
      and acquired immune deficiency syndrome (HIV/AIDS) patients, and to find out the
      clinical characteristics of abnormal savda syndrome type HIV/AIDS patients.
      METHODS: Between June and July in 2012, 307 eligible HIV/AIDS patients from in
      patient department and out-patient clinics of Xinjiang Uighur Autonomous Region
      the Sixth People's Hospital in Urumqi were investigated. TUM syndrome
      differentiation was performed by a senior TUM physician. Each participant
      completed a Sign and Symptom Check-List for Persons Living with HIV/AIDS (SSC
      HIV) questionnaire. Depression was evaluated by using Hamilton Rating Scale for
      Depression Questionnaire. Blood specimen was collected from each participant to
      test the levels of blood chemicals. RESULTS: Of 307 HIV/AIDS patients, 189
      (61.6%) were abnormal savda syndrome type, 118 (38.4%) were non-abnormal-savda
      syndrome type. Mean CD4 counts of abnormal savda syndrome type patients was
      (227.61+/-192.93) cells/uL, and the prevalence of anemia, thrombocytopenia, and
      elevated cystatin C were 49.7%, 28.6%, and 44.7%, which were significantly higher
      than those in the non-abnormal-savda syndrome type patients (26.3%, 16.0% and
      25.0%,P<0.05). In addition, depression (79.9%) and HIV/AIDS-related symptoms such
      as fatigue (42.3%), back aches (40.7%), lack of appetite (33.9%), night sweats
      (31.7%) were more common among abnormal savda syndrome patients (P<0.05).
      CONCLUSION: Abnormal savda syndrome is the dominant syndrome among HIV/AIDS
      patients, and they present a more sever clinical manifestation.

PMID- 25749904
TI  - Comparison of Shenfu Injection () and epinephrine on catecholamine levels in a
      porcine model of prolonged cardiac arrest.
AB  - OBJECTIVE: To compare the effects of Shenfu Injection (SFI) and epinephrine (EPI)
      on catecholamine levels in a porcine model of prolonged cardiac arrest (CA).
      METHODS: After 8 min of untreated ventricular fibrillation, 24 Wuzhishan
      miniature pigs were randomly assigned to one of the three groups (n=8 per group)
      and received central venous injection, respectively: SFI group (1 mL/kg), EPI
      group (20 MUg/kg EPI), and normal saline (NS) group. Cardiac output (CO), maximum
      rate of increase/decrease in left ventricular pressure (+/-dp/dt), serum levels
      of EPI, norepinephrine (NE), and dopamine (DA) were determined at baseline and at
      0.5, 1, 2, and 4 h after restoration of spontaneous circulation. RESULTS: The
      duration of cardiopulmonary resuscitation was shorter in the EPI and SFI groups
      than in the NS group (P<0.05). The EPI level increased significantly after
      restoration of spontaneous circulation (ROSC) in all three groups, and was
      significantly different between the EPI group and the other two groups
      immediately after ROSC (both P<0.01), but these differences gradually disappeared
      over time. There were no significant differences in NE or DA levels among the
      three groups, and there were no correlations between catecholamine levels and CO
      or dp/dt (P>0.05). CONCLUSIONS: SFI did not significantly affect endogenous
      catecholamine levels during cardiopulmonary resuscitation after prolonged
      ventricular fibrillation. However, SFI improved oxygen metabolism, and produced a
      better hemodynamic status compared with EPI. SFI might be a potentially
      vasopressor drug for the treatment of CA.

PMID- 25749905
TI  - Evaluation of the cholinergic hypothesis in Alzheimer's disease with
      neuropsychological methods.
AB  - AIM: This study aimed at evaluating the cholinergic hypothesis in Alzheimer's
      disease (AD) patients utilizing the pupillometry method, cognitive tests and
      Hamilton Depression Rating Scale (HAM-D), as well as to examine whether a
      correlation between cognitive tests and pupillometry exists. METHODS: Forty-two
      patients with mean age 69.2 +/- 7.0 years and documented AD volunteered to
      participate in this study, while 33 healthy matched subjects served as controls.
      All subjects underwent a pupillometric measurement and performed the Wechsler
      Memory Scale (WMS) and Mini Mental State Examination (MMSE). Also, HAM-D was used
      to assess the severity of depressive symptoms. The pupillometric parameters
      studied were (1) latency for the onset of constriction (T1), (2) maximum
      constriction velocity (VCmax), and (3) maximum constriction acceleration (ACmax).
      RESULTS: In AD patients MMSE and WMS score were correlated with ACmax (r = 
      0.409, p < 0.05 and r = -0.513, p < 0.05, respectively) and VCmax (r = -0.664, p
      < 0.05 and r = -0.771, p < 0.05), respectively. Moreover, T1 was found to be
      significantly increased by 23 % (p < 0.05) in AD patients compared to healthy
      subjects. Conversely, the mean scores of VCmax and ACmax were significantly
      decreased in AD patients by 46 % (p < 0.05) and by 47 % (p < 0.05), respectively,
      as compared to healthy subjects. There was no significant difference between the
      two groups for HAM-D. Additionally, AD patients showed decreased score in WMS by
      40 % (p < 0.05) and in MMSE by 28.5 % (p < 0.05) compared to healthy subjects. Of
      the indices that were studied VCmax and ACmax are governed mainly by the action
      of the Parasympathetic Nervous System. CONCLUSIONS: The results of this study
      demonstrated that there is a correlation between cognitive tests and pupillometry
      in AD patients. Thus, pupillometry could be considered as a sensitive technique
      for the investigation of cholinergic deficits, which indirectly lead to memory
      and cognitive disorders in AD patients.

PMID- 25749906
TI  - Phthalate Metabolites in Urine Samples from School Children in Taipei, Taiwan.
AB  - In 2011, Taiwan authorities reported that two phthalates, including di-(2
      ethylhexyl) phthalate and di-iso-nonyl phthalate, were intentionally introduced
      into a variety of foods and beverages during the course of 15 years. However,
      little is known about body burdens of phthalate contaminations in local
      residents, especially children recently living in Taiwan. In the present study,
      five target phthalate metabolite analytes-including mono-methyl phthalate, mono
      ethyl phthalate, mono-n-butyl phthalate (MBP), mono-benzyl phthalate (MBzP), and
      mono-(2-ethylhexyl) phthalate (MEHP)-in spot urine samples were analyzed by way
      of high performance liquid chromatography-tandem mass spectrometry-mass
      spectrometry. All of the urine samples were collected from 225 healthy school
      children between 12 and 15 years of age (average 13.6) in the Taipei area,
      Taiwan, between 2009 and 2010. As the dominant urinary phthalate metabolites in
      Taiwanese school children, MEHP and MBP contributed 61 and 29 % of all of the
      target analytes, respectively. MEHP had the highest median of 29.8 MUg/g
      creatinine (range of 13.1-72.8), which was greater than those reported for school
      children in the other countries during the same period, whereas MBP had a median
      of 14.3 MUg/g creatinine (range 7.91-27.8). Statistically, urinary concentrations
      of MBP, MBzP, and MEHP were determined to have significantly positive
      correlations with the ages of Taiwanese school children (p < 0.05). Furthermore,
      urinary levels of MBzP in male children were considerably greater than those in
      female children (p = 0.006). 

PMID- 25749907
TI  - Albert W. Frenkel (1919-2015): photosynthesis research pioneer, much-loved
      teacher, and scholar.
AB  - Albert W. Frenkel, a pioneer in photosynthesis research, and discoverer of
      photophosphorylation in photosynthetic bacteria, is remembered here by two of us:
      Govindjee (historical corner editor of photosynthesis research) and Susanna
      Frenkel (SF; Albert Frenkel's daughter, who provided most of the family
      information). 

PMID- 25749908
TI  - Demonstration of the effectiveness of zinc in diarrhoea of children living in
      Switzerland.
AB  - We designed a double-blinded randomized clinical trial of zinc (10 or 20 mg of
      zinc sulphate for 2-5 month-old or 6-59 month-old children, respectively, during
      10 days) vs. placebo in otherwise healthy children aged 2 months to 5 years who
      presented with acute diarrhoea (i.e. >=3 stools/day for less than 72 h). Eighty
      seven patients (median age 14 months; range 3.1-58.3) were analysed in an
      intention-to-treat approach. Forty-two patients took zinc and 45 placebo. There
      was no difference in the duration nor in the frequency of diarrhoea, but only 5%
      of the zinc group still had diarrhoea at 120 h of treatment compared to 20% in
      the placebo group (P = 0.05). Thirty-one patients (13 zinc and 18 placebo) were
      available for per-protocol analyses. The median (IQR) duration of diarrhoea in
      zinc-treated patients was 47.5 h (18.3-72) and differed significantly from the
      placebo group (median 76.3; IQR 52.8-137) (P = 0.03). The frequency of diarrhoea
      was also lower in the zinc group (P = 0.02). CONCLUSION: zinc treatment decreases
      the frequency and severity of diarrhoea in children aged 2 months to 5 years
      living in Switzerland. However, the intention-to-treat analysis reveals
      compliance issues that question the proper duration of treatment and the choice
      of optimal pharmaceutical formulation.

PMID- 25749909
TI  - Influence of disordered packing pattern on elastic modulus of single-stranded DNA
      film on substrate.
AB  - Determining mechanical properties of single-stranded DNA film grafted on gold
      surface is critical for analysis and design of DNA-microcantilever biosensors.
      However, it remains an open issue to quantify the relations among the disordered
      packing patterns of DNA chains, the mechanical properties of DNA film and the
      resultant biodetection signals. In this paper, first, the bending experiment of
      microcantilever is carried out to provide the basic data for a refined multi
      scale model of microcantilever deflection induced by ssDNA immobilization. In the
      model, the complicated interactions in DNA film (consisting of DNA, water
      molecules and salt ions) are simplified as effective interactions among coarse
      grained soft cylinders, which can reveal the varieties of DNA structure in the
      circumstances of different lengths and salt concentrations; Ohshima's
      distribution of net charge density is employed to incorporate compositional
      variations of salt ions along the thickness direction into the Strey's mesoscopic
      empirical potential on molecular interactions in DNA solutions, and the related
      model parameters for ssDNA film on substrate are obtained from the curve fitting
      with our microcantilever bending experiment. Second, the effect of nanoscopic
      distribution of DNA chains on elastic modulus of ssDNA film is studied by a
      thought experiment of uniaxial compression, and the disordered patterns of DNA
      chains are generated by Monte Carlo method. Simulation results point out that
      nanoscale ssDNA film shows size effect, gradient and diversity in elastic modulus
      and can achieve maximum stiffness by preferring a disordered and energetically
      favorable packing pattern collectively induced by electrostatic force, hydration
      force and configurational entropy. 

PMID- 25749910
TI  - The Duesseldorf warning signs for primary immunodeficiency: is it time to change
      the rules?
AB  - OBJECTIVE: Different sets of warning signs can be used if primary
      immunodeficiency (PID) is suspected: those of the Jeffrey Modell Foundation
      (JMF), the German Patients' Organisation for Primary Immunodeficiencies (DSAI)
      and the Association of the Scientific Medical Societies in Germany (AWMF). A few
      studies have tested the JMF criteria, with unconvincing results, but the
      diagnostic models of the DSAI and AWMF have not been tested at all. We set out to
      establish the utility of these three scoring systems and compare them with our
      own set of five warning signs (Duesseldorf criteria). DESIGN: Prospective study.
      PATIENTS: Two hundred ten patients admitted to our hospital between 2010 and 2012
      with suspected PID. RESULTS: PID were found in 36 (17 %) of the patients
      admitted. Of the established sets of warning signs, the JMF and the DSAI had
      inadequate sensitivity, while the DSAI and the AWMF showed insufficient
      specificity. Our own criteria were analyzed with regard to maximal specificity
      and sensitivity (Youden Index) and sensitivity and yielded NPV of 0.89 and 0.91
      respectively. Youden index revealed combination of five signs and symptoms:
      lymphopenia, otitis media >7, failure to thrive, failure to grow normally,
      pneumonia >1. For maximum negative predictive value the following set was found:
      lymphopenia, hypogammglobulinemia, failure to thrive, growth disorders, iv
      antibiotics and abscesses. CONCLUSION: In contrast to the new, evaluated
      Duesseldorf criteria, all three established sets of warning signs proved
      inadequate for preselection of patients for admission to specialized PID centers.
      The Duesseldorf criteria should now being tested in further studies.

PMID- 25749911
TI  - The effect of LDL particles on the behaviour of epithelial noncancer and cancer
      cell lines after in vitro induced injury.
AB  - Cell spreading capability and cell proliferation are the major processes in wound
      healing of injured epithelia as well as in tumour progression. The effect of low
      density lipoprotein (LDL) particles as a major extracellular source of
      cholesterol was evaluated in the re-epithelisation assay of in vitro induced
      injury. We selected two noncancer cell lines with different dependence on LDL
      concentrations, the kidney epithelial cells (MDCK) with higher dependence and
      keratinocytes (HaCaT) with lower dependence on LDL, and three cancer cell lines
      originating from epithelial cells: A549 (alveolar), CaCo-2 (intestinal) and RT4
      (urothelial). All cells were incubated in a control medium, in an LDL-enriched
      medium or in an LDL-deficient medium. The LDL-enriched medium stimulated cell
      spreading of MDCK cells which, together with increased proliferation of these
      cells, resulted in an enhanced re-epithelisation of in vitro induced injury. LDL
      deficiency caused lower cell spreading which resulted in a decreased re
      epithelisation despite the higher proliferation of MDCK cells in this medium. The
      re-epithelisation of keratinocytes (HaCaT) was not affected by altered LDL
      concentrations. In cancer cell lines A549, CaCo-2 and RT4, wide heterogeneity
      regarding cell proliferation and spreading capability was observed after
      treatment with different LDL concentrations. LDL had no influence on actin
      filament and tight junction distribution in any of the tested cell lines. The
      cholesterol content of all cell types, except for CaCo-2 cells, proved to be
      independent of the LDL level. Further research of the beneficial effects of LDL
      is needed to prove LDL as a safe enhancer of epithelial wound healing. 

PMID- 25749912
TI  - Hydroxysafflor yellow A (HYSA) inhibited the proliferation and differentiation of
      3T3-L1 preadipocytes.
AB  - Hydroxysafflor yellow A (HSYA), a main component of safflor yellow, has been
      demonstrated to prevent steroid-induced avascular necrosis of femoral head by
      inhibiting primary bone marrow-derived mesenchymal stromal cells adipogenic
      differentiation induced by steroid. In this study, we investigate the effect of
      HSYA on the proliferation and adipogenesis of mouse 3T3-L1 preadipocytes. The
      effects of HSYA on proliferation and differentiation of 3T3-L1 cells and its
      possible mechanism were studied by 3-(4,5-dimethylthiazol-2-yl) 2,5-diphenyl
      tetrazolium bromide spectrophotometry, Oil Red O staining, intracellular
      triglyceride assays, real-time quantitative RT-PCR, transient transfection and
      dual luciferase reporter gene methods. HSYA inhibited the proliferation of 3T3-L1
      preadipocytes and cell viability greatly decreased in a dose and time dependent
      manner. HSYA (1 mg/l) notably reduced the amount of intracellular lipid and
      triglyceride content in adipocytes by 21.3 % (2.13 +/- 0.36 vs 2.71 +/- 0.40, P <
      0.01) and 22.6 % (1.33 +/- 0.07 vs 1.72 +/- 0.07, P < 0.01) on days 8 following
      the differentiation, respectively. HSYA (1 mg/l) significantly increased hormone
      sensitive lipase (HSL) mRNA expression and promoter activities by 2.4- and 1.55
      fold, respectively (P < 0.01), in differentiated 3T3-L1 adipocytes. HSYA inhibits
      the proliferation and adipogenesis of 3T3-L1 preadipocytes. The inhibitory action
      of HYSA on adipogenesis may be due to the promotion of lipolytic-specific enzyme
      HSL expression by increasing HSL promoter activity. 

PMID- 25749913
TI  - Development and characterization of a monoclonal antibody against the putative T
      cells of Labeo rohita.
AB  - In this study, we have described the development and characterization of
      monoclonal antibodies (MAbs) directed against thymocytes of rohu, Labeo rohita.
      MAbs were obtained by immunizing BALB/c mice with freshly isolated and nylon wool
      column enriched mononuclear cells of thymus. Positive clones against thymocytes
      were screened by cellular ELISA. The hybridoma showing strong reactivity with
      nylon wool enriched mononuclear cells, and non-reactivity with a rohu thymus
      macrophage cell line and rohu serum was selected and subjected to single cell
      cloning by limiting dilution. The MAbs secreted by a positive clone were
      designated as E6 MAb. Western blotting of reduced protein from enriched
      thymocytes showed that E6 reacted with a 166.2 kDa polypeptide and belongs to the
      IgG1 subclass. Flow cytometric analysis of gated lymphocytes, revealed that the
      percentage of E6 positive (E6+) cells in thymus (n = 5, 720.4 +/- 79.70 g) was
      89.7 %. Similarly, the percentage of E6+ cells in kidney, spleen and blood (n =
      5) was 6.71, 1.71 and 1.88 %, respectively. In indirect immunoperoxidase test,
      E6+ cells appeared to be lymphoid cells with a high nucleus to cytoplasmic ratio
      and were densely packed in the central region of thymus whereas, a few cells were
      found to be positive in kidney and spleen sections. E6 MAb also reacted with a
      small population of lymphocytes in blood smear. This MAb appears to be a suitable
      marker for T lymphocytes and can be a valuable tool in studying immune response
      and ontogeny of L. rohita immune system. 

PMID- 25749915
TI  - Development of an optimized 5-stage protocol for the in vitro preparation of
      insulin-secreting cells from mouse ES cells.
AB  - In order to produce insulin-secreting cells with a high value of glucose
      stimulated insulin secretion (GSIS) from mouse embryonic stem cells, we have
      developed an optimized 5-stage protocol by referring to culture conditions so far
      reported elsewhere. This protocol is characterized by 4 points: (1) use of an
      activin-free medium in the first stage, (2) use of gelatin/fibronectin coated
      culture dishes in 1-4 stages throughout, (3) removal of undifferentiated cells by
      cell sorter at the end of 4th stage, and (4) sedimental culture in the 5th stage.
      GSIS value of the produced cells reached 2.4, that was at a higher rank of those
      so far reported. The produced cells were transplanted in diabetes model mice but
      no remedy effect was observed. Then transplantation was conducted in pre-diabetes
      model mice, in which GSIS was impaired without affecting insulin producing
      function. The transplantation of 5 * 10(6) cells resulted in a marked improvement
      of glucose tolerance within 20 days. This effect decreased but was still observed
      at 120 days post-transplantation. This demonstrates the feasibility of the novel
      optimized protocol. 

PMID- 25749914
TI  - Developments in techniques for the isolation, enrichment, main culture conditions
      and identification of spermatogonial stem cells.
AB  - The in vitro culture system of spermatogonial stem cells (SSCs) provides a basis
      for studies on spermatogenesis, and also contributes to the development of new
      methods for the preservation of livestock and animal genetic modification. In
      vitro culture systems have mainly been established for mouse SSCs, but are
      lacking for farm animals. We reviewed and analyzed the current progress in SSC
      techniques such as isolation, purification, cultivation and identification. Based
      on the published studies, we concluded that two-step enzyme digestion and
      magnetic-activated cell sorting are fast becoming the main methods for isolation
      and enrichment of SSCs. With regard to the culture systems, serum and feeders
      were earlier thought to play an important role in the self-renewal and
      proliferation of SSCs, but serum- and feeder-free culture systems as a means of
      overcoming the limitations of SSC differentiation in long-term SSC culture are
      being explored. However, there is still a need to establish more efficient and
      ideal culture systems that can also be used for SSC culture in larger mammals.
      Although the lack of SSC-specific surface markers has seriously affected the
      efficiency of purification and identification, the transgenic study is helpful
      for our identification of SSCs. Therefore, future studies on SSC techniques
      should focus on improving serum- and feeder-free culture techniques, and
      discovering and identifying specific surface markers of SSCs, which will provide
      new ideas for the optimization of SSC culture systems for mice and promote
      related studies in farm animals. 

PMID- 25749916
TI  - Novel physiological insight into a lotus root appearance in stable coronary
      artery diseases; Report of two cases.
AB  - So far physiological significance of multiple intraluminal channels separated by
      thin wall structures, so called "a lotus root appearance", in an angiographic
      insignificant lesion in patients with suspected angina pectoris has remained
      undetermined. Here we present two cases that showed a "reverse visual-functional
      mismatch" phenomenon of a lotus root appearance using the indexes of myocardial
      fractional flow reserve and/or coronary flow velocity reserve. Our findings may
      provide a novel physiological insight into a lotus root appearance as a high
      possibility of critical functional stenosis in those with stable coronary artery
      diseases. 

PMID- 25749919
TI  - Teaching Cultural Competence to Psychiatry Residents: Seven Core Concepts and
      Their Implications for Therapeutic Technique.
AB  - The authors describe the Tulane Model for teaching cultural competence to
      psychiatry residents in order to outline an innovative approach to curricula
      development in academic psychiatry. The authors focus on the didactic experience
      that takes place during the first and second postgraduate years and present seven
      core concepts that should inform the emerging clinician's thinking in the
      formulation of every clinical case. The authors discuss the correspondence
      between each core concept and the Outline for Cultural Formulation, introduced in
      Diagnostic and Statistical Manual of Mental Disorders (DSM)-IV and updated in DSM
      5. The authors illustrate how each of the core concepts is utilized as a
      guideline for teaching residents a process for eliciting culturally relevant
      information from their patients and their personal histories and how to apply
      that knowledge in the assessment and treatment of patients in clinical settings. 

PMID- 25749917
TI  - Functional neuroanatomical correlates of episodic memory impairment in early
      phase psychosis.
AB  - Studies have demonstrated that episodic memory (EM) is often preferentially
      disrupted in schizophrenia. The neural substrates that mediate EM impairment in
      this illness are not fully understood. Several functional magnetic resonance
      imaging (fMRI) studies have employed EM probe tasks to elucidate the neural
      underpinnings of impairment, though results have been inconsistent. The majority
      of EM imaging studies have been conducted in chronic forms of schizophrenia with
      relatively few studies in early phase patients. Early phase schizophrenia studies
      are important because they may provide information regarding when EM deficits
      occur and address potential confounds more frequently observed in chronic
      populations. In this study, we assessed brain activation during the performance
      of visual scene encoding and recognition fMRI tasks in patients with earlyphase
      psychosis (n = 35) and age, sex, and race matched healthy control subjects (n =
      20). Patients demonstrated significantly lower activation than controls in the
      right hippocampus and left fusiform gyrus during scene encoding and lower
      activation in the posterior cingulate, precuneus, and left middle temporal cortex
      during recognition of target scenes. Symptom levels were not related to the
      imaging findings, though better cognitive performance in patients was associated
      with greater right hippocampal activation during encoding. These results provide
      evidence of altered function in neuroanatomical circuitry subserving EM early in
      the course of psychotic illness, which may have implications for
      pathophysiological models of this illness.

PMID- 25749918
TI  - Transcatheter closure of patent ductus arteriosus: 11 years of clinical
      experience in Cipto Mangunkusumo Hospital, Jakarta, Indonesia.
AB  - Transcatheter closure of patent ductus arteriosus (PDA) has been suggested to be
      the standard treatment of PDA. Although, in general, the procedure shows a high
      successful rate, outcomes may vary among pediatric cardiology centers. To
      evaluate the effectiveness of transcatheter closure of PDA in Cipto Mangunkusumo
      Hospital, Jakarta, Indonesia, this was a retrospective study on patients who
      underwent transcatheter closure of PDA in Cipto Mangunkusumo Hospital during the
      period of 2002-2013. Hospital registry was reviewed and data about patients'
      characteristics, PDA severity, procedure, and outcomes were retrieved. There were
      298 patients, of whom 90 were males, who underwent transcatheter closure of PDA
      during the study period. Median age was 3.4 years (1 months-18 years), and median
      body weight was 12 (3.6-59) kg. The diameter of PDA ranged from 1.1 to 15.4 mm
      with a median of 3.7 mm. Device could be deployed in all patients, in which most
      were the Amplatzer ductal occluder (69.8 %) and the remainders were coils. Median
      fluoroscopy time was 15.4 (1.5-87) min, and procedure time was 76 (30-200) min.
      Complete closure was achieved in most patients (97.3 %), whereas device migration
      occurred in a minority (0.3 %) of patients. No major complication occurred during
      or after the procedure. Transient anemia and bradycardia were found in 3.7 and
      1.3 % patients, respectively. Most patients were discharged from the hospital at
      1 day after the procedure. Transcatheter closure method is a safe and effective
      procedure to close PDA.

PMID- 25749920
TI  - The Impact of Medical School on Student Mental Health.

PMID- 25749921
TI  - Design and Piloting of an Integrated Neuroscience Elective for Medical Students
      in Their Clinical Clerkships.

PMID- 25749922
TI  - The Time is Now: Improving Substance Abuse Training in Medical Schools.
AB  - This commentary highlights the growing demand for substance abuse prevention and
      treatment, summarizes the literature regarding the current insufficiencies in
      substance abuse training in medical schools, and suggests strategies to address
      this gap in physician education. The authors describe how the combination of
      mandated coverage for substance abuse services and expanding treatment needs
      means that more physicians, regardless of their patient populations, will be
      faced with addressing the problem of substance use. The authors review the
      literature on substance abuse training in medical schools, which indicates
      insufficient exposure to this topic. The authors describe how current substance
      abuse training at medical schools is focused on transmitting scientific knowledge
      with relatively little education or training in attitudes and skills central to
      effective prevention and treatment. Given the gap between clinical need and
      physician education, the authors suggest several strategies for medical schools
      to increase training in substance abuse knowledge, attitudes, and skills, which
      will enhance the practice of evidence-based care. The authors posit that medical
      curricular reform, combined with initiatives to change clinical culture around
      substance abuse, will translate into improved rates of screening, shorter overall
      length of treatment, effective referrals for continued treatment, and increased
      access to care for individuals who use substances and so reduce the morbidity and
      mortality associated with substance use. 

PMID- 25749923
TI  - Geriatric psychiatry in the psychiatry clerkship: a survey of current education
      practices.
AB  - OBJECTIVE: The aging of the US population and shortage of geriatric psychiatrists
      mean that all medical students must be prepared to evaluate psychiatric symptoms
      in older patients. The authors sought to describe current geriatric psychiatry
      teaching practices during the psychiatry clerkship. METHODS: Psychiatry clerkship
      directors at 110 American medical schools were surveyed about didactic and
      clinical experiences of geriatric psychiatry. RESULTS: Sixty-two (56 %) of
      programs responded. One fifth of programs lacked specific instruction in
      geriatric psychiatry. Programs were more likely to include instruction on
      dementia than late-life depression. Increased geriatric psychiatry educational
      offerings were associated with the following: number of geriatric psychiatrists
      on faculty, presence of a geriatric psychiatrist on the medical education
      committee, and inclusion of geriatric psychiatry specific items in clerkship
      learning objectives. CONCLUSIONS: Current practices in some clerkships are
      inadequate to prepare medical students to care for older patients with
      psychiatric symptoms.

PMID- 25749924
TI  - Evaluating Psychometric Properties of the Spanish-version of the Pediatric
      Functional Assessment of Chronic Illness Therapy-Perceived Cognitive Function
      (pedsFACIT-PCF).
AB  - PURPOSE: The pediatric Functional Assessment of Chronic Illness Therapy-Perceived
      Cognitive Function (pedsFACIT-PCF) is a 13-item short-form derived from the
      pediatric Perceived Cognitive Function item bank (pedsPCF), which was developed
      to measure children's daily cognitive behaviors and was validated on the US
      general population and children with cancer. This study evaluated the
      psychometric properties of Spanish language pedsFACIT-PCF and the measurement
      equivalence between Spanish and English versions. METHODS: pedsFACIT-PCF items
      were translated into Spanish using a standard iterative methodology. A total of
      1358 English- and 604 Spanish-speaking children aged 8-17 years who completed
      English and Spanish versions of pedsFACIT-PCF, respectively, were administered
      through an Internet survey company. Unidimensionality was evaluated using
      confirmatory factor analysis. Item responses were modeled using item response
      theory. The presence and impact of differential item functioning (DIF) were
      evaluated using ordinal logistic regression. RESULTS: Unidimensionality of the
      pedsFACIT-PCF was supported. One of the 13 items demonstrated statistically
      significant DIF by language; however, impacts of language DIF on both individual
      scores and at the test level were negligible. No Spanish items showed DIF with
      respect to age and gender. CONCLUSIONS: The 13-item pedsFACIT-PCF demonstrated
      stable measurement properties on language, gender and age and can be used for
      future trials.

PMID- 25749925
TI  - A longitudinal analysis on pain treatment satisfaction among Chinese patients
      with chronic pain: predictors and association with medical adherence, disability,
      and quality of life.
AB  - BACKGROUND: Patient satisfaction research in chronic pain treatment is scarce
      internationally and is nonexistent in Chinese communities like Hong Kong. This
      longitudinal study examined the relationships between medical adherence, pain
      treatment satisfaction, disability, and quality of life (QoL) in a sample of
      Chinese patients with chronic pain. METHODS: A total of 178 patients with chronic
      pain were assessed at baseline, 3 and 6 months following baseline. Medical
      adherence and pain treatment satisfaction were assessed by the Participant
      Compliance Reporting Scale and the Pain Treatment Satisfaction Scale (PTSS),
      respectively. QoL, depression, pain catastrophizing, and pain-related fear were
      assessed using SF-12, the depression subscale of the Hospital Anxiety and
      Depression Scale (HADS-D), the Pain Catastrophizing Scale, and the Tampa Scale
      for Kinesiophobia, respectively. Linear mixed effects models (LME) were fitted to
      identify predictors of pain treatment satisfaction, medical adherence, and QoL.
      RESULTS: Results of univariate LME analyses showed significant quadratic time
      effects on four PTSS scores and significant associations between disability grade
      and PTSS scores (all p < 0.05). Medical adherence was not significantly
      associated with satisfaction regarding pain medication (model 1). Satisfaction
      with medication characteristics emerged as an independent predictor of medical
      adherence (model 2: std beta = -0.11, p < 0.05) after controlling for
      sociodemographic and pain variables. Neither medical adherence nor pain treatment
      satisfaction predicted QoL outcomes (models 3 and 4). CONCLUSIONS: Distinct
      trajectories in pain treatment satisfaction were displayed in the current sample
      of Chinese patients with different disability grading chronic pain. Within pain
      treatment, only medication characteristics significantly impacted patients'
      medical adherence.

PMID- 25749926
TI  - Comparison of the Biological Impacts of the Fluoride Compounds by Graphical Risk
      Visualization Map Technique.
AB  - Various fluoride compounds are widely used in industry. The present risk
      assessment study was conducted using a series of inorganic binary fluorides of
      the type XFn, where X(n) = Na(+), K(+), Li(+), Mg(2+), Ca(2+), Sr(2+), Ba(2+),
      Al(3+), Nd(3+), La(3+), Ce(3+), Sm(3+), Gd(3+), Y(3+), Yb(2+), and Zn(2+). The
      aqueous solutions of these salts were orally administrated to 16 experimental
      groups (one for each of the salts tested). The levels of fluoride, N-acetyl-beta
      D-glucosaminidase in cumulative 24-h urine samples and creatinine clearance were
      measured to assess possible acute renal damages. The levels of fluoride, alanine
      aminotransferase, and aspartate aminotransferase were also determined in serum
      samples to assess possible acute hepatic damages. The results reveal that sodium
      fluoride (NaF), potassium fluoride (KF), and zinc fluoride tetrahydrate (ZnF2
      (.)4H2O) can carry the fluoride ion into the bloodstream and that it is excreted
      via urine more readily than the other compounds tested. These fluorides were
      assigned the highest risk impact factor. Most of the rare earth fluorides are
      insoluble in water while those groups 2 and 13 of the periodic table are slightly
      soluble, so that they do not have a significant negative risk. These findings
      suggest that the biological impact of fluoride depends on the accompanying
      counter ion and its solubility. The risk map obtained in the present study shows
      that the graphical visualization map technique employed is a valuable new tool to
      assess the toxicological risk of chemical compounds. 

PMID- 25749927
TI  - Effects of Dietary Cadmium and Boron Supplementation on Performance, Eggshell
      Quality and Mineral Concentrations of Bone in Laying Hens.
AB  - This study was conducted to determine the effects of supplementation of different
      levels of cadmium and boron on performance, eggshell quality, and mineral
      concentrations of bone in layer diets. In this trial, a total of 144 layer
      chickens, 21 weeks old, were randomly divided into 12 experimental groups. In
      each experimental group, there were four replicates, and in each of the
      replicates, there were three hens. Experimental diets consisted of all possible
      combinations of four levels of added cadmium (0, 5, 15, and 45 mg/kg) and three
      levels of added boron (0, 60, and 120 mg/kg) to the basal diet. Added cadmium (15
      or 45 mg/kg) had a significant adverse effect on performance parameters (P <
      0.01). Eggshell thickness increased with the addition of 5 mg/kg level of cadmium
      to the diet (P < 0.01). Tibia cadmium content increased with the addition of
      cadmium and boron in the diet (P < 0.01). However, tibia boron content decreased
      with the supplementation of cadmium (P < 0.01). These results indicate that the
      addition of boron to the diet did not prevent adverse effect of cadmium on
      performance and eggshell quality, or accumulation of cadmium in bone. 

PMID- 25749928
TI  - Non-Hodgkin lymphoma in pediatric patients with common variable immunodeficiency.
AB  - Common variable immunodeficiency (CVID) is a heterogeneous primary
      immunodeficiency associated with an increased risk of malignancy in adulthood,
      with lymphoma as one of the major causes of death. The aim of this study is to
      describe those malignancies detected in our cohort of pediatric CVID patients. We
      reviewed the clinical and laboratory data and the treatments and their outcomes
      in all pediatric CVID patients from our institution that developed a neoplasia.
      Four malignancies were diagnosed in three out of 27 pediatric CVID patients.
      Three malignancies were non-Hodgkin lymphoma (NHL) of B cell origin (mean age at
      diagnosis: 8 years old), and the remaining was a low-grade astrocytoma. Among
      NHL, two were mucosa-associated lymphoid tissue (MALT) lymphomas and one was
      associated with Epstein-Barr virus infection. NHL developed before CVID diagnosis
      in two patients. CVID patients showed different clinical phenotypes and belonged
      to different groups according Euroclass and Pediatric classification criteria.
      CONCLUSIONS: Malignancies, especially lymphoma, may develop in pediatric CVID
      patients with no previous signs of lymphoid hyperplasia and even before CVID
      diagnosis. Consequently, strategies for cancer prevention and/or early diagnosis
      are required in pediatric CVID patients.

PMID- 25749930
TI  - Closure of Melanoma Defects on the Sole of the Foot Using Glaborous Skin: The End
      of the Flap?
AB  - INTRODUCTION: Plantar melanomas are a challenge to reconstruct after wide
      excision. Non-glaborous skin grafts have resulted in tissue loss, hyperkeratosis,
      marginal scarring, and poor functional outcomes, leading many to utilize various
      flaps for reconstruction that are technically demanding and associated with
      increased failure rates. Glaborous skin is better suited to withstand compressive
      and shear forces, and provides a more robust graft for plantar defects. METHODS:
      Data were collected prospectively. Wide excision to the plantar fascia and
      sentinel lymph node biopsies were performed as indicated. The defect was treated
      with negative pressure dressings until granulation tissue was flush with
      surrounding skin. Two 8/1000 inch grafts were harvested from the ipsilateral non
      weight-bearing instep. The epidermis/papillary dermis was replaced on the donor
      site and the deeper glaborous dermal graft was secured to the defect. This
      technique is demonstrated in the multimedia file. Primary endpoints were graft
      take, complication rates, and functional outcomes. RESULTS: Consecutive plantar
      melanomas of the foot were prepared for glaborous grafting. Mean Breslow
      thickness was 3.9 mm (range 1.25-10; n = 5), and the average width of the defect
      was 6.2 cm. Mean follow-up was 304 days. The graft take was 100 %, and pre- and
      post-surgery results are displayed in the media file and Fig. 1. There were no
      recipient site complications, incidences of significant hypo- or
      hyperpigmentation, or hypertrophic scarring at either site. One patient
      experienced a donor site hematoma without delayed healing or hypertrophic
      scarring. There were no other donor or recipient site complications. Cosmesis was
      excellent, with minimal to no residual contour irregularity. Functional outcomes
      demonstrated a 100 % return to baseline activities without orthotics, including
      snowboarding and windsurfing. CONCLUSION: Glabrous dermal grafting of plantar
      defects after melanoma resection is extremely reliable, affords excellent
      cosmesis, has minimal to no donor site morbidity, and results in excellent
      functional outcomes. Flaps are now rarely performed for these patients at our
      institution. Fig. 1 Plantar melanoma defect before and after split-thickness
      glaborous skin grafting using the current technique.

PMID- 25749929
TI  - Protective role of cannabinoid receptor 2 activation in
      galactosamine/lipopolysaccharide-induced acute liver failure through regulation
      of macrophage polarization and microRNAs.
AB  - Acute liver failure (ALF) is a potentially life-threatening disorder without any
      effective treatment strategies. d-Galactosamine (GalN)/lipopolysaccharide (LPS)
      induced ALF is a widely used animal model to identify novel hepato-protective
      agents. In the present study, we investigated the potential of a cannabinoid
      receptor 2 (CB2) agonist, JWH-133 [(6aR,10aR)-3-(1,1-dimethylbutyl)-6a,7,10,10a
      tetrahydro-6,6,9-trimethyl-6H-dibenzo[b,d]pyran], in the amelioration of GalN/LPS
      induced ALF. JWH-133 treatment protected the mice from ALF-associated mortality,
      mitigated alanine transaminase and proinflammatory cytokines, suppressed
      histopathological and apoptotic liver damage, and reduced liver infiltration of
      mononuclear cells (MNCs). Furthermore, JWH-133 pretreatment of M1/M2-polarized
      macrophages significantly increased the secretion of anti-inflammatory cytokine
      interleukin-10 (IL-10) in M1 macrophages and potentiated the expression of M2
      markers in M2-polarized macrophages. In vivo, JWH-133 treatment also suppressed
      ALF-triggered expression of M1 markers in liver MNCs, while increasing the
      expression of M2 markers such as Arg1 and IL-10. microRNA (miR) microarray
      analysis revealed that JWH-133 treatment altered the expression of only a few
      miRs in the liver MNCs. Gene ontology analysis of the targets of miRs suggested
      that Toll-like receptor (TLR) signaling was among the most significantly targeted
      cellular pathways. Among the altered miRs, miR-145 was found to be the most
      significantly decreased. This finding correlated with concurrent upregulated
      expression of its predicted target gene, interleukin-1 receptor-associated kinase
      3, a negative regulator of TLR4 signaling. Together, these data are the first to
      demonstrate that CB2 activation attenuates GalN/LPS-induced ALF by inducing an M1
      to M2 shift in macrophages and by regulating the expression of unique miRs that
      target key molecules involved in the TLR4 pathway. 

PMID- 25749932
TI  - Molecular Pathogenesis and Targeted Therapy of Pancreatic Cancer.
AB  - Accumulation of multiple genetic and/or epigenetic abnormalities is required for
      generation and progression of cancers, and the survival of cancer cells might
      depend on addiction to these abnormalities. Because disruption of such dependency
      on the abnormal molecules should cause the cancer cell death, so-called oncogene
      addiction is the rationale for molecular targeted therapy. Pancreatic cancer,
      especially pancreatic ductal adenocarcinoma, is one of the most lethal
      malignancies in humans, and remains a challenging problem in targeted therapy
      compared to other malignancies such as pancreatic neuroendocrine tumor. This
      review summarizes the molecular pathogenesis of pancreatic cancer on the basis of
      the recent studies of driver mutations including chromatin remodeling factors,
      and promising concepts "cancer stemness" and "stromal niche" for the strategy of
      novel targeted therapy. 

PMID- 25749931
TI  - Long-Term Outcomes of Conversion Hepatectomy for Initially Unresectable
      Colorectal Liver Metastases.
AB  - BACKGROUND: Chemotherapy, including molecular targeted agents, for metastatic
      colorectal cancer has greatly improved recently and offers an increased chance of
      conversion hepatectomy for patients with initially unresectable liver metastases.
      However, the long-term outcomes of conversion hepatectomy remain controversial.
      METHODS: We retrospectively assessed a consecutive series of 210 patients with
      colorectal liver metastases to evaluate the long-term outcomes of patients who
      underwent conversion hepatectomy and to clarify the predictive factors related to
      the conversion rate. RESULTS: Ninety-four cases were initially resectable and
      underwent primary hepatectomy. Of the 116 patients with initially unresectable
      liver metastases, 104 patients underwent chemotherapy (systemic or hepatic artery
      infusion). Twenty-four percent (11/46) of the initially unresectable liver
      limited metastases that became resectable after chemotherapy were subsequently
      treated with conversion hepatectomy; however, there were no cases of conversion
      among the patients with extrahepatic metastases. The final resection rate of
      liver metastases was 50 % (105/210), including conversion hepatectomies. The
      predicted 5-year survival rate in the conversion hepatectomy group was 76 %. The
      conversion rate was significantly (P < 0.05) higher in patients with liver
      limited metastases (24 %), patients with no LN involvement (27 %), the hepatic
      arterial infusion chemotherapy group (33 %), patients treated with anti-EGFR
      agents (21 %), and patients with a complete or partial response (33 %).
      CONCLUSIONS: Twenty-four percent of the patients with initially unresectable
      liver-limited metastases became resectable after chemotherapy, and the survival
      rate after conversion hepatectomy was not inferior to that of the primary
      hepatectomy cases. Chemotherapy regimens with high response rates are needed to
      achieve a higher conversion rate.

PMID- 25749933
TI  - Prevalence and comorbidity of mental disorders among adolescents living in
      residential youth care.
AB  - Most adolescents are placed in residential youth care (RYC) because of severe
      psychosocial strains and child maltreatment, which represent risk factors for
      developing mental disorders. To plan RYC units and ensure that residents receive
      evidence-based psychiatric interventions, it is necessary to obtain reliable and
      valid prevalence estimates of mental disorders in this population. However, there
      is a lacuna of research on diagnoses derived from standardized clinical
      interviews. The aim of this study was to assess the prevalence and comorbidity of
      mental disorders applying diagnostic interviews in an entire population of
      adolescents living in RYC in Norway. All young people in RYC were invited to
      participate in the study. Eighty-six RYC institutions with 601 eligible
      adolescents were included and 400 adolescents, 12-20 years old, participated in
      the study, yielding a response rate of 67 %. Anonymous Child Behaviour Checklist
      scores for 141 (70 %) of the declining residents were also available, allowing
      diagnoses according to the Diagnostic and Statistical Manual of Mental Disorders
      Fourth Edition (DSM-IV) for 541 youths to be estimated. Diagnoses were assessed
      by trained interviewers with the Child and Adolescent Psychiatric Assessment
      interview (CAPA). Seventy-six point two per cent (71.5-80.8 CI 95 %) of
      adolescents received at least one 3-month DSM-IV diagnosis. Prevalence rates for
      internalizing psychiatric disorders were higher than for behavioural disorders.
      Comorbidity was high between these two groups. Mental disorders were prevalent
      among children and youth in RYC. Our results create major concerns and challenge
      the existing organization of the RYC system.

PMID- 25749934
TI  - The Relationship Between Colonic Macrophages and MicroRNA-128 in the Pathogenesis
      of Slow Transit Constipation.
AB  - BACKGROUND: Recent evidence suggests that colonic macrophages and microRNAs play
      important roles in motor activity in the gastrointestinal tract. However, there
      are almost no data concerning colonic macrophages and microRNAs in slow transit
      constipation. AIM: The purpose of this study was to investigate colonic
      macrophages and microRNA-128 expression in the pathogenesis of slow transit
      constipation in colon tissues. METHODS: Full-thickness colonic specimens from
      patients undergoing surgery for slow transit constipation, due to refractoriness
      to other therapeutic interventions (n = 25), were compared to controls (n = 25),
      and the number of colonic macrophages (as evaluated by specific monoclonal
      antibodies) was counted. Gene expression analysis of microRNA-128 was performed
      by microRNA microarray and qRT-PCR. Lastly, bioinformatics analysis, coupled with
      luciferase reporter assays, was used to investigate the mRNA transcript(s)
      targeted by microRNA-128. RESULTS: Compared to controls, 20 of 25 slow transit
      constipation patients (80 %) had significantly higher numbers of macrophages in
      colonic specimens, coupled with down-regulation of microRNA-128. Linear
      regression analyses showed a significant negative correlation between macrophage
      number and microRNA-128 expression level. Among 83 bioinformatically predicated
      candidates, mitogen-activated protein kinase 14 (p38alpha) was validated to be a
      direct target of microRNA-128 in human intestinal epithelial cells. CONCLUSIONS:
      This study presents evidence for the negative correlation of macrophage number
      and microRNA-128 expression, in slow transit constipation patients, representing
      a possible mechanism of impaired gastrointestinal motility.

PMID- 25749935
TI  - Gut microbiota: a key player in health and disease. A review focused on obesity.
AB  - Gut microbiota, its evolutive dynamics and influence on host through its
      protective, trophic and metabolic actions, has a key role in health and opens
      unique opportunities for the identification of new markers of the
      physiopathological state of each individual. Alterations in gut microbiota
      composition have been associated with plenty disorders. Of interest, the vast
      number of studies demonstrates the role of microbiota in obesity, a serious
      public health problem that has reached epidemic proportions in many developed and
      middle-income countries. The economic and health costs of this condition and its
      comorbidities such as fatty liver, insulin resistance/diabetes, or cardiovascular
      events are considerable. Therefore, every strategy designed to reduce obesity
      would imply important savings. Targeting microbiota, in order to restore/modulate
      the microbiota composition with antibiotics, probiotics, prebiotics, or even
      fecal transplants, is considered as a promising strategy for the development of
      new solutions for the treatment of obesity. However, there is still lot to do in
      this field in order to identify the exact composition of microbiota in "health"
      and the specific mechanisms that regulate the host-microbiotal crosstalk. In
      addition, it is important to note that changes not only in the gut microbiota
      profile (abundance) but also in its metabolism and functions need to be taken
      into account in the context of contribution in the physiopathology of obesity and
      related disorders. 

PMID- 25749936
TI  - The association between alterations of eye movement control and cerebral
      intrinsic functional connectivity in Parkinson's disease.
AB  - Patients with Parkinson's disease (PD) present with eye movement disturbances
      that accompany the cardinal motor symptoms. Previous studies have consistently
      found evidence that large-scale functional networks are critically involved in
      eye movement control. We challenged the hypothesis that altered eye movement
      control in patients with PD is closely related to alterations of whole-brain
      functional connectivity in association with the neurodegenerative process.
      Saccadic and pursuit eye movements by video-oculography and 'resting-state'
      functional MRI (3 Tesla) were recorded from 53 subjects, i.e. 31 patients with PD
      and 22 matched healthy controls. Video-oculographically, a broad spectrum of eye
      movement impairments was demonstrated in PD patients vs. controls, including
      interrupted smooth pursuit, hypometric saccades, and a high distractibility in
      anti-saccades. Significant correlations between altered oculomotor parameters and
      functional connectivity measures were observed, i.e. the worse the oculomotor
      performance was, the more the regional functional connectivity in cortical,
      limbic, thalamic, cerebellar, and brainstem areas was decreased. Remarkably,
      decreased connectivity between major nodes of the default mode network was
      tightly correlated with the prevalence of saccadic intrusions as a measure for
      distractability. In conclusion, dysfunctional eye movement control in PD seems to
      be primarily associated with (cortical) executive deficits, rather than being
      related to the ponto-cerebellar circuits or the oculomotor brainstem nuclei.
      Worsened eye movement performance together with the potential pathophysiological
      substrate of decreased intrinsic functional connectivity in predominantly
      oculomotor-associated cerebral functional networks may constitute a behavioral
      marker in PD. 

PMID- 25749937
TI  - The Gut Microbiota of Workers of the Litter-Feeding Termite Syntermes wheeleri
      (Termitidae: Syntermitinae): Archaeal, Bacterial, and Fungal Communities.
AB  - The gut microbiota of termites allows them to thrive on a variety of different
      materials such as wood, litter, and soil. For that reason, they play important
      roles in the decomposition of biomass in diverse biomes. This function is
      essential in the savanna, where litter-feeding termites are one of the few
      invertebrates active during the dry season. In this study, we describe the gut
      microbiota of workers (third and fourth instars) of the species Syntermes
      wheeleri, a litter-feeding termite from the Brazilian savanna. Results of 16S and
      18S ribosomal RNA (rRNA) gene-targeted pyrosequencing using primers sets specific
      to each domain have revealed its bacterial, archaeal, and fungal diversities.
      Firmicutes accounted for more than half of the operational taxonomic units of the
      Bacteria domain. The most abundant fungal species were from the class
      Dothideomycetes of the phylum Ascomycota. The methanogenic orders
      Methanobacteriales, Methanosarcinales, and Methanomicrobiales of the phylum
      Euryarchaeota accounted for the greatest part of the Archaea detected in this
      termite. A comparison of the gut microbiota of the two instars revealed a
      difference in operational taxonomic unit (OTU) abundance but not in species
      richness. This description of the whole gut microbiota represents the first study
      to evaluate relationships among bacteria, archaea, fungi, and host in S.
      wheeleri. 

PMID- 25749938
TI  - Effects of forest management practices in temperate beech forests on bacterial
      and fungal communities involved in leaf litter degradation.
AB  - Forest management practices (FMPs) significantly influence important ecological
      processes and services in Central European forests, such as leaf litter
      decomposition and nutrient cycling. Changes in leaf litter diversity, and thus,
      its quality as well as microbial community structure and function induced by
      different FMPs were hypothesized to be the main drivers causing shifts in
      decomposition rates and nutrient release in managed forests. In a litterbag
      experiment lasting 473 days, we aimed to investigate the effects of FMPs (even
      aged timber management, selective logging and unmanaged) on bacterial and fungal
      communities involved in leaf litter degradation over time. Our results showed
      that microbial communities in leaf litter were strongly influenced by both FMPs
      and sampling date. The results from nonmetric multidimensional scaling (NMDS)
      ordination revealed distinct patterns of bacterial and fungal successions over
      time in leaf litter. We demonstrated that FMPs and sampling dates can influence a
      range of factors, including leaf litter quality, microbial macronutrients, and
      pH, which significantly correlate with microbial community successions. 

PMID- 25749939
TI  - Laparoscopic colon and rectal resections with intracorporeal anastomosis and
      trans-vaginal specimen extraction for colorectal cancer. A case series and
      systematic literature review.
AB  - PURPOSE: Intracorporeal anastomosis associated to trans-vaginal specimen
      extraction decreases the extent of colon mobilisation and the number and size of
      abdominal incisions, improving the benefits of minimally invasive surgery in
      female patients. The aim of this study was to evaluate the safety and
      effectiveness of this procedure for colorectal cancer. METHODS: Between 2009 and
      2013, 13 female patients underwent laparoscopic colon and rectal resection for
      colorectal cancer with intracorporeal anastomosis and trans-vaginal specimen
      extraction: 2 right colectomies, 1 transverse colon resection, 4 left colectomies
      and 6 anterior resections were performed. A MEDLINE search of publications on the
      presented procedure for colon neoplasms was carried out. RESULTS: There were no
      intraoperative complications and no conversions. Postoperative visual analogue
      scale (VAS) score in the pelvis, abdomen and shoulder was moderate. In the
      postoperative period, we observed two colorectal anastomotic strictures,
      successfully treated with pneumatic endoscopic dilation. Median length of the
      specimen was 18.5 cm, with a median tumour size of 5.5 cm in diameter. Median
      number of retrieved lymph nodes was 12. All circumferential resection margins
      were negative. During a mean follow-up of 31 months (range, 6-62), there was
      neither evidence of recurrent disease nor disorders related to the genitourinary
      system. The aesthetic outcome was considered satisfactory in all patients. Nine
      studies were identified in the systematic review. CONCLUSIONS: Our case series,
      according to the results of the literature, showed that intracorporeal
      anastomosis associated to trans-vaginal specimen extraction is feasible and safe
      in selected female patients.

PMID- 25749940
TI  - Regulatory, legislative, and policy updates with anticoagulant use.
AB  - Thromboembolism afflicts millions of patients annually in the United States and
      is associated with a significant cost burden. Recent advances in oral
      anticoagulation have provided clinicians with more options for management of
      these diseases. Accordingly, regulatory, legislative, and policy-making
      organizations have intervened with the aim of improving patient outcomes,
      ensuring patient safety, and reducing costs. There have been a number of recent
      developments in surveillance, litigation, and regulatory oversight that
      clinicians should recognize. In this review article we summarize key updates
      related to the management of anticoagulant therapy as it relates to thrombosis
      prevention and treatment. 

PMID- 25749941
TI  - Affinity chromatography: a historical perspective.
AB  - Affinity chromatography is one of the most selective and versatile forms of
      liquid chromatography for the separation or analysis of chemicals in complex
      mixtures. This method makes use of a biologically related agent as the stationary
      phase, which provides an affinity column with the ability to bind selectively and
      reversibly to a given target in a sample. This review examines the early work in
      this method and various developments that have lead to the current status of this
      technique. The general principles of affinity chromatography are briefly
      described as part of this discussion. Past and recent efforts in the generation
      of new binding agents, supports, and immobilization methods for this method are
      considered. Various applications of affinity chromatography are also summarized,
      as well as the influence this field has played in the creation of other affinity
      based separation or analysis methods. 

PMID- 25749942
TI  - Protein purification by aminosquarylium cyanine dye-affinity chromatography.
AB  - Affinity chromatography (AC) is one of the most important techniques for the
      separation and purification of biomolecules, being probably the most selective
      technique for protein purification. It is based on unique specific reversible
      interactions between the target molecule and a ligand. In this affinity
      interaction, the choice of the ligand is extremely important for the success of
      the purification protocol. The growing interest in AC has motivated an intense
      research effort toward the development of materials able to overcome the
      disadvantages of conventional natural ligands, namely their high cost and
      chemical and biological lability. In this context, synthetic dyes have emerged,
      in recent decades, as a promising alternative to biological ligands. Herein,
      detailed protocols for the assembling of a new chromatographic dye-ligand
      affinity support bearing an immobilized aminosquarylium cyanine dye on an agarose
      based matrix (Sepharose CL-6B) and for the separation of a mixture o f three
      standard proteins: lysozyme, alpha-chymotrypsin, and trypsin are provided.

PMID- 25749943
TI  - One-step purification of phosphinothricin acetyltransferase using reactive dye
      affinity chromatography.
AB  - Reactive dye purification is an affinity purification technique offering unique
      selectivity and high purification potential. Historically, purification of
      phosphinothricin acetyltransferase (PAT) has involved several steps of
      precipitation and column chromatography. Here, we describe a novel purification
      method that is simple, time-saving, inexpensive, and reproducible. The novel
      method employs a single chromatography step using a reactive dye resin, Reactive
      brown 10-agarose. Reactive brown 10 preferentially binds the PAT protein, which
      can then be specifically released by one of its substrates, acetyl-CoA. Using
      Reactive brown 10-agarose, PAT protein can be purified to homogeneity from E.
      coli or plant tissue with high recovery efficiency. 

PMID- 25749944
TI  - Antibody purification from human plasma by metal-chelated affinity membranes.
AB  - Immobilized metal ion affinity chromatography (IMAC) has been used for
      purification of proteins. IMAC introduces a new approach for selectively
      interacting biomolecules on the basis of their affinities for metal ions. The
      separation is based on different binding abilities of the proteins to the
      chelated metal ions on support. Here, N-methacryloyl-(L)-histidine methyl ester
      (MAH) is used as the metal-chelating ligand. Poly(hydroxyethyl methacrylate)
      Poly(HEMA) based membranes were prepared by photo-polymerization technique. Then,
      Zn(2+), Ni(2+), Co(2+), and Cu(2+) ions were chelated directly on the poly(HEMA
      MAH) membranes for purification of immunoglobulin G (IgG) from human plasma. 

PMID- 25749945
TI  - Specific recognition of supercoiled plasmid DNA by affinity chromatography using
      a synthetic aromatic ligand.
AB  - Liquid chromatography is the method of choice for the purification of plasmid DNA
      (pDNA), since it is simple, robust, versatile, and highly reproducible. The most
      important features of a chromatographic procedure are the use of suitable
      stationary phases and ligands. As conventional purification protocols are being
      replaced by more sophisticated and selective procedures, the focus changes toward
      designing and selecting ligands of high affinity and specificity. In fact, the
      chemical composition of the chromatographic supports determines the interactions
      established with the target molecules, allowing their preferential retention over
      the undesirable ones. Here it is described the selective recognition and
      purification of supercoiled pDNA by affinity chromatography, using an
      intercalative molecule (3,8-diamino-6-phenylphenanthridine) as ligand. 

PMID- 25749946
TI  - Cell affinity separations on microfluidic devices.
AB  - Separating cells from a heterogeneous sample on microfluidic devices is a very
      important unit operation in biological and medical research. Microfluidic
      affinity cell chromatography is a label-free separation technique, providing ease
      of operation, low cost, and rapid analysis. In this chapter, protocols for cell
      affinity separation in polydimethylsiloxane (PDMS)-glass microdevices and glass
      capillaries are described. 

PMID- 25749947
TI  - Aptamer-modified magnetic beads in affinity separation of proteins.
AB  - Aptamers are valuable alternative ligands for affinity separations. Here, we
      describe the aptamer-based affinity separation of His-tagged proteins using an
      aptamer directed against the His-tag. The immobilization of the aptamer to
      magnetic beads is described as well as the aptamer-based purification and proper
      methods for the characterization of the process. Moreover, indications for the
      transfer of the process to other aptamers are given. 

PMID- 25749948
TI  - The Strep-tag system for one-step affinity purification of proteins from
      mammalian cell culture.
AB  - The Strep-tag-or its improved version Strep-tagII-is an eight amino acid sequence
      that can be easily fused or conjugated to any protein or peptide of interest and
      that was engineered for high affinity toward streptavidin, which otherwise is
      widely known as a tight biotin-binding reagent. Especially in combination with
      immobilized Strep-Tactin, a mutant streptavidin specifically optimized toward the
      Strep-tagII, this system enables the facile one-step affinity purification of
      various biomolecules, including oligomeric and even membrane proteins. The Strep
      tagII/Strep-Tactin interaction shows exquisite specificity, thus allowing
      efficient separation from host cell proteins, and it can be reversed simply by
      addition of biotin (or a suitable derivative thereof, such as desthiobiotin).
      Therefore, this system has become very popular for the highly efficient affinity
      chromatography under biochemically mild conditions. Here, we describe the
      purification of Strep-tagged proteins from mammalian cell lysates and cell
      culture supernatants. 

PMID- 25749949
TI  - Robotic high-throughput purification of affinity-tagged recombinant proteins.
AB  - Affinity purification of recombinant proteins has become the method of choice to
      obtain good quantities and qualities of proteins for a variety of downstream
      biochemical applications. While manual or FPLC-assisted purification techniques
      are generally time-consuming and labor-intensive, the advent of high-throughput
      technologies and liquid handling robotics has simplified and accelerated this
      process significantly. Additionally, without the human factor as a potential
      source of error, automated purification protocols allow for the generation of
      large numbers of proteins simultaneously and under directly comparable
      conditions. The delivered material is ideal for activity comparisons of different
      variants of the same protein. Here, we present our strategy for the simultaneous
      purification of up to 24 affinity-tagged proteins for activity measurements in
      biochemical assays. The protocol described is suitable for the scale typically
      required in individual research laboratories. 

PMID- 25749950
TI  - Macroporous silica particles derivatized for enhanced lectin affinity enrichment
      of glycoproteins.
AB  - This chapter details procedures for (1) functionalizing macroporous silica
      particles with lectins, a class of proteins that have affinity for the glycan
      moieties on glycoproteins, and (2) utilizing the lectin-silica material for high
      performance affinity chromatography (HPAC) to enrich glycoproteins from small
      volumes of biological sample materials. 

PMID- 25749951
TI  - Immobilized magnetic beads-based multi-target affinity selection coupled with
      HPLC-MS for screening active compounds from traditional Chinese medicine and
      natural products.
AB  - Screening and identifying active compounds from traditional Chinese medicine
      (TCM) and other natural products plays an important role in drug discovery. Here,
      we describe a magnetic beads-based multi-target affinity selection-mass
      spectrometry approach for screening bioactive compounds from natural products.
      Key steps and parameters including activation of magnetic beads, enzyme/protein
      immobilization, characterization of functional magnetic beads, screening and
      identifying active compounds from a complex mixture by LC/MS, are illustrated.
      The proposed approach is rapid and efficient in screening and identification of
      bioactive compounds from complex natural products. 

PMID- 25749952
TI  - Mixed-bed affinity chromatography: principles and methods.
AB  - Mixed-bed chromatography is far from being a well-established technology within
      the panoply of bioseparation tools. Composed of an assembly of distinct sorbents
      that are mixed in a single bed, they have been mostly developed in the last
      decade for the reduction of dynamic concentration range where they allowed
      discovering many low-copy proteins within very complex proteomes. Other
      interesting preparative applications of mixed-bed chromatography have since been
      developed. In this chapter the basic concepts first and then detailed application
      recipes are described for (1) the reduction of protein dynamic concentration
      range, (2) the removal of impurity traces at the last stage of a biopurification
      process, and (3) the selection and use of sorbents as mixed bed in protein
      purification.

PMID- 25749953
TI  - Preparation and characterization of fluorophenylboronic acid-functionalized
      affinity monolithic columns for the selective enrichment of cis-diol-containing
      biomolecules.
AB  - Boronate affinity monolithic columns have been developed into an important means
      for the selective recognition and capture of cis-diol-containing biomolecules,
      such as glycoproteins, nucleosides and saccharides. The ligands of boronic acids
      are playing an important role in boronate affinity monolithic columns. Although
      several boronate affinity monoliths with high affinity toward cis-diol-containing
      biomolecules have been reported, only few publications are focused on their
      detailed procedures for preparation and characterization. This chapter describes
      in detail the preparation and characterization of a boronate affinity monolithic
      column applying 2,4-difluoro-3-formyl-phenylboronic acid (DFFPBA) as a ligand.
      The DFFPBA-functionalized monolithic column not only exhibited an ultrahigh
      boronate affinity toward cis-diol-containing biomolecules, but also showed great
      potential for the selective enrichment of cis-diol-containing biomolecules in
      real samples. 

PMID- 25749954
TI  - Introduction to macroporous cryogels.
AB  - Cryogels are highly elastic three-dimensional materials consisting of a network
      of interconnected macropores. This unique morphology combined with high
      mechanical and chemical stability provides excellent mass flow properties. The
      matrices are synthesized at subzero temperatures from almost any gel-forming
      precursor. The main fields of application are in biotechnology as 3D-scaffold for
      cell cultivation, and tissue engineering, or bioseparation as chromatographic
      media for the separation and purification of biomolecules. This chapter briefly
      highlights the preparation, properties, and application of these materials. 

PMID- 25749955
TI  - Cryogels with affinity ligands as tools in protein purification.
AB  - Affinity chromatography is one of the well-known separation techniques especially
      if high purity is desired. Introducing ligands on monolithic structure gives the
      possibility for purifying complex media such as plasma and crude extract. This
      chapter is focusing on the preparation of cryogels as monolithic column and
      immobilization of concanavalin A on its surface as ligand for capturing the
      glycoprotein horseradish peroxidase. 

PMID- 25749956
TI  - Direct capture of His6-tagged proteins using megaporous cryogels developed for
      metal-ion affinity chromatography.
AB  - Immobilized metal-ion affinity chromatography (IMAC) has been developed for the
      rapid isolation and purification of recombinant proteins. In this chapter,
      megaporous cryogels were synthesized having metal-ion affinity functionality, and
      their adsorptive properties were investigated. These cryogels have large pore
      sizes ranging from 10 to 100 MUm with corresponding porosities between 80 and
      90%. The synthesized IMAC-cryogel had a total ligand density of 770 MUmol/g.
      Twelve milligram of a His6-tagged protein (NAD(P)H-dependent 2-cyclohexen-1-one
      reductase) can be purified from a crude cell extract per gram of IMAC-cryogels.
      The protein binding capacity is increased with higher degrees of grafting,
      although a slight decrease in column efficiency may result. This chapter provides
      methodologies for a rapid single-step purification of recombinant His6-tagged
      proteins from crude cell extracts using IMAC-cryogels.

PMID- 25749957
TI  - Ni(II) chelated IDA functionalized poly(HEMA-GMA) cryogels for urease adsorption.
AB  - Cryogelic support materials have been intensively used for the purification and
      separation of biomolecules. Cryogels are cheap materials, they can be easily used
      for different purposes and their chemical and physical stabilities are very high.
      Cryogels can also be easily functionalized with different type of ligands and are
      be applicable to different affinity systems. Within these affinity systems,
      immobilized metal affinity chromatography (IMAC) offers efficient and simple
      protein purification strategies. IMAC technology has been deeply applied to
      bioseparations studies. In the present chapter, the preparation of a cryogel
      support material and the functionalization with the chelating agent iminodiacetic
      acid (IDA) and the subsequent Ni(II) chelation are described. Characterization
      techniques and the cryogel preparation method are summarized and urease
      adsorption studies on the metal chelate cryogel are briefly explained. 

PMID- 25749958
TI  - A novel chromatographic media: histidine-containing composite cryogels for HIgG
      separation from human serum.
AB  - Histidine-containing microspheres (HCM) with 2 MUm in size were synthesized by
      suspension polymerization of poly(hydroxyethyl methacrylate) and N-methacryloyl-L
      histidine methyl ester. Then, they were used to prepare composite cryogel columns
      by an embedding process for affinity depletion of immunoglobulin G (HIgG) from
      human serum via histidine groups on microspheres. Here, we describe HIgG
      adsorption performance of composite cryogel columns in both aqueous solution and
      human serum.

PMID- 25749959
TI  - Molecularly imprinted cryogels for human serum albumin depletion.
AB  - Molecularly imprinted polymers can be used for the selective capture of a target
      molecule from complex medium. Cryogels novel matrices, which characterized by
      their supermacropores that makes their use advantageous when studying with
      biological samples. By combining high selectivity of the molecular imprinting
      approach with using cryogel as a base polymer, in this protocol, preparation of
      the albumin-imprinted cryogels is described. This material is a useful candidate
      for the selective albumin depletion from the human serum sample prior to the
      detailed proteomic analysis. 

PMID- 25749960
TI  - Interpenetrating polymer network composite cryogels with tailored porous
      morphology and sorption properties.
AB  - Cryogels, by their particular morphology and mechanical properties, proved to be
      invaluable materials in biomedicine and biotechnology as carriers for molecules
      and cells, chromatographic materials for cell separations and cell culture.
      Methods used in the characterization of porosity and sorption properties of
      cryogels are very needful tools, which assist the investigator in the decision on
      the performances of the gel. Herein, we describe the preparation of ionic
      interpenetrating polymer network composite cryogels and the characterization
      methods of their porous morphology, and then the methods used for testing their
      sorption properties for ionic dyes used as models for drugs. 

PMID- 25749961
TI  - Analysis of drug-protein interactions by high-performance affinity
      chromatography: interactions of sulfonylurea drugs with normal and glycated human
      serum albumin.
AB  - High-performance affinity chromatography (HPAC) is a type of liquid
      chromatography that has seen growing use as a tool for the study of drug-protein
      interactions. This report describes how HPAC can be used to provide information
      on the number of binding sites, equilibrium constants, and changes in binding
      that can occur during drug-protein interactions. This approach will be
      illustrated through recent data that have been obtained by HPAC for the binding
      of sulfonylurea drugs and other solutes to the protein human serum albumin (HSA),
      and especially to forms of this protein that have been modified by non-enzymatic
      glycation. The theory and use of both frontal analysis and zonal elution
      competition studies in such work will be discussed. Various practical aspects of
      these experiments will be presented, as well as factors to consider in the
      extension of these methods to other drugs and proteins or additional types of
      biological interactions. 

PMID- 25749962
TI  - Accurate protein-peptide titration experiments by nuclear magnetic resonance
      using low-volume samples.
AB  - NMR spectroscopy allows measurements of very accurate values of equilibrium
      dissociation constants using chemical shift perturbation methods, provided that
      the concentrations of the binding partners are known with high precision and
      accuracy. The accuracy and precision of these experiments are improved if
      performed using individual capillary tubes, a method enabling full automation of
      the measurement. We provide here a protocol to set up and perform these
      experiments as well as a robust method to measure peptide concentrations using
      tryptophan as an internal standard. 

PMID- 25749963
TI  - Characterization of the binding strengths between boronic acids and cis-diol
      containing biomolecules by affinity capillary electrophoresis.
AB  - The affinity of boronic acids toward cis-diol-containing biomolecules has found
      wide applications in many fields, such as sensing, separation, drug delivery, and
      functional materials. A sound understanding of the binding interactions will
      greatly facilitate exquisite applications of this chemistry. Traditional
      techniques are associated with some apparent drawbacks, so they are only
      applicable to a limited range of boronic acids and cis-diol-containing
      biomolecules. This chapter describes an affinity capillary electrophoresis (ACE)
      method for the characterization of the binding strengths between boronic acids
      and cis-diol-containing biomolecules. As compared with existing approaches, such
      as (11)B NMR, the ACE method exhibits several significant advantages: (1)
      possibility of simultaneous study of multiple interactions, (2) low requirement
      on the purity of the binding species, (3) widely applicable to almost all types
      of cis-diol-containing compounds and boronic acids, and (4) high accuracy and
      precision. 

PMID- 25749964
TI  - Determination of the kinetic rate constant of cyclodextrin supramolecular systems
      by high-performance affinity chromatography.
AB  - The kinetics of the association and dissociation are fundamental kinetic
      processes for the host-guest interactions (such as the drug-target and drug
      excipient interactions) and the in vivo performance of supramolecules. With
      advantages of rapid speed, high precision and ease of automation, the high
      performance affinity chromatography (HPAC) is one of the best techniques to
      measure the interaction kinetics of weak to moderate affinities, such as the
      typical host-guest interactions of drug and cyclodextrins by using a cyclodextrin
      immobilized column. The measurement involves the equilibration of the
      cyclodextrin column, the upload and elution of the samples (non-retained
      substances and retained solutes) at different flow rates on the cyclodextrin and
      control column, and data analysis. It has been indicated that cyclodextrin
      immobilized chromatography is a cost-efficient high-throughput tool for the
      measurement of (small molecule) drug-cyclodextrin interactions as well as the
      dissociation of other supramolecules with relatively weak, fast, and extensive
      interactions. 

PMID- 25749965
TI  - Molecular modeling of the affinity chromatography of monoclonal antibodies.
AB  - Molecular modeling is a methodology that offers the possibility of studying
      complex systems such as protein-ligand complexes from an atomistic point of view,
      making available information that can be difficultly obtained from experimental
      studies. Here, a protocol for the construction of molecular models of the
      interaction between antibodies and ligands that can be used for an affinity
      chromatography process is presented. The outlined methodology focuses mostly on
      the description of a procedure that may be adopted to determine the structure and
      free energy of interaction between the antibody and the affinity ligand. A
      procedure to extend the proposed methodology to include the effect of the
      environment (buffer solution, spacer, support matrix) is also briefly outlined. 

PMID- 25749966
TI  - Testosterone in men with hypogonadism and high cardiovascular risk, Pros.
AB  - Although numerous randomized studies have shown that testosterone replacement
      therapy (TRT) improves intermediate outcomes in patients at risk and in those
      with proven cardiovascular disease (CVD), results derived mainly from registries
      and observational studies have suggested an increased cardiovascular risk in
      elderly men receiving often supra-therapeutic doses of testosterone. Recent meta
      analyses have shown that when testosterone has been used in patients with pre
      existing cardiovascular conditions, the effect on the disease has been either
      beneficial or neutral. Similar results have been reported in hypo- and eugonadal
      men. Contrasting results have been reported by two trials of testosterone
      treatment in frail elderly men. Reports from poorly analyzed databases have
      reported an increased risk of cardiovascular events with testosterone use. More
      recently, a population-based study showed no increased cardiovascular risk of
      testosterone replacement in hypogonadal men. Available data from controlled
      clinical trials suggest that the use of testosterone in elderly men does not
      increase cardiovascular risk nor the risk of events. Studies in men with CVD,
      angina, or heart failure report a benefit from testosterone replacement in men
      with or without hypogonadism. Therefore, at present, the cardiovascular benefits
      of TRT in elderly men outweigh the risks. This is particularly evident in those
      men with pre-existing CVD. 

PMID- 25749967
TI  - Genome-wide patterns of genetic variation among silkworms.
AB  - Although the draft genome sequence of silkworm is available for a decade, its
      genetic variations, especially structural variations, are far from well explored.
      In this study, we identified 1,298,659 SNPs and 9,731 indels, of which 32 % of
      SNPs and 92.2 % of indels were novel compared to previous silkworm re-sequencing
      analysis. In addition, we applied a read depth-based approach to investigate copy
      number variations among 21 silkworm strains at genome-wide level. This effort
      resulted in 562 duplicated and 41 deleted CNV regions, and among them 442 CNV
      were newly identified. Functional annotation of genes affected by these genetic
      variations reveal that these genes include a wide spectrum of molecular
      functions, such as immunity and drug detoxification, which are important for the
      adaptive evolution of silkworms. We further validated the predicted CNV regions
      using q-PCR. 94.7 % (36/38) of the selected regions show divergent copy numbers
      compared to a single-copy gene OR2. In addition, potential presence/absence
      variations are also observed in our study: 11 genes are present in the reference
      genome, but absent in other strains. Overall, we draw an integrative map of
      silkworm genetic variation at genome-wide level. The identification of genetic
      variations in this study improves our understanding that these variants play
      important roles in shaping phenotypic variations between wild and domesticated
      silkworms.

PMID- 25749972
TI  - From histones to ribosomes: a chromatin regulator tangoes with translation.
AB  - Histone lysine methylation is a critical regulator of chromatin-templated
      processes such as gene transcription and DNA repair, and is dynamically
      controlled by enzymes that write and erase this posttranslational modification.
      Although histone methylation has been well studied, the functions of nonhistone
      lysine methylation and its regulatory enzymes, particularly outside the nucleus,
      are poorly defined. In this issue of Cancer Discovery, Van Rechem and colleagues
      shed light on a new role for the lysine demethylase KDM4A as a regulator of
      protein translation and identify a single-nucleotide polymorphism in the KDM4A
      gene as a candidate biomarker for mTOR inhibitor therapy.

PMID- 25749973
TI  - Targeting ETV1 in gastrointestinal stromal tumors: tripping the circuit breaker
      in GIST?
AB  - Activating mutations in the KIT or PDGFRA receptor tyrosine kinase genes are the
      key oncogenic drivers in the majority of gastrointestinal stromal tumors (GIST),
      but novel results now show that aberrant kinase signaling is potentiated by a
      positive feedback circuit that involves the ETS transcription factor ETV1.
      Targeting ETV1 can disrupt this circuit and represents a promising new
      therapeutic approach for the treatment of GISTs.

PMID- 25749974
TI  - Aberrant cytokine production by nonmalignant cells in the pathogenesis of
      myeloproliferative tumors and response to JAK inhibitor therapies.
AB  - Kleppe and colleagues use detailed cytokine profiling analyses to investigate the
      role of aberrant proinflammatory cytokine secretion in the pathogenesis of
      myeloproliferative neoplasms. Their analyses implicate constitutive activation of
      STAT3 in both malignant and nonmalignant bone marrow cell populations as a driver
      of aberrant cytokine secretion and as a cellular target mediating the therapeutic
      activity of ruxolitinib.

PMID- 25749975
TI  - Design and Fabrication of an MRI-Compatible, Autonomous Incubation System.
AB  - Tissue engineers have long sought access to an autonomous, imaging-compatible
      tissue incubation system that, with minimum operator handling, can provide real
      time visualization and quantification of cells, tissue constructs, and organs.
      This type of screening system, capable of operating noninvasively to validate
      tissue, can overcome current limitations like temperature shock, unsustainable
      cellular environments, sample contamination, and handling/stress. However, this
      type of system has been a major challenge, until now. Here, we describe the
      design, fabrication, and characterization of an innovative, autonomous incubation
      system that is compatible with a 9.4 T magnetic resonance imaging (MRI) scanner.
      Termed the e-incubator (patent pending; application number: 13/953,984), this
      microcontroller-based system is integrated into an MRI scanner and noninvasively
      screens cells and tissue cultures in an environment where temperature, pH, and
      media/gas handling are regulated. The 4-week study discussed herein details the
      continuous operation of the e-incubator for a tissue-engineered osteogenic
      construct, validated by LIVE/DEAD((r)) cell assays and histology. The evolving MR
      quantitative parameters of the osteogenic construct were used as biomarkers for
      bone tissue engineering and to further validate the quality of the product
      noninvasively before harvesting. Importantly, the e-incubator reliably
      facilitates culturing cells and tissue constructs to create engineered tissues
      and/or investigate disease therapies. 

PMID- 25749976
TI  - Transient stop-flow arm arterial-venous equilibrium pressure measurement:
      determination of precision of the technique.
AB  - Transient stop-flow arm arterial-venous equilibrium pressure (Pmsf-arm) is a
      validated technique for measuring the mean systemic filling pressure (Pmsf). Pmsf
      is a functional measure of the effective intravascular volume status. This study
      aims to assess the precision of the Pmsf-arm measurement. Pmsf-arm was measured
      by inflating a pneumatic tourniquet around the upper arm 50 mmHg above systolic
      pressure for 60 s, four times consecutively, with an interval of 5 min. Arterial
      (Pa) and venous pressure (Pv) were recorded every 10 s. Pa-Pv difference was
      calculated to determine the stop-flow time. The coefficient error (CE) was
      determined and used to derive the least significant change (LSC) in Pmsf-arm that
      this technique could reliably detect. The rANOVA test was used to compare
      repeated measurements of the four determinations of Pmsf-arm. 80 measurements of
      Pmsf-arm were studied in 20 patients. Pa and Pv equalised after 60 s of inflation
      (Pa-Pv difference 0 +/- 0.01 mmHg). There were no significant differences of Pmsf
      arm values among determinations. For a single measurement, the CE was 5 % (+/-2
      %) and the LSC was 14 % (+/-5 %). Averaging two, three and four measurements the
      CE improves to 4 % (+/-1 %), 3 % (+/-1 %) and 3 % (+/-1 %) respectively, and the
      LSC was reduced to 10 % (+/-4 %), 8 % (+/-3 %) and 7 % (+/-3 %) respectively. One
      measurement of Pmsf-arm can reliably detect changes on Pmsf-arm of 14 %. The
      precision of Pmsf-arm technique improves when averaging two or three
      measurements. 

PMID- 25749977
TI  - In vitro evaluation of an ultrasonic cardiac output monitoring (USCOM) device.
AB  - Non-invasive cardiac output monitoring techniques provide high yield, low risk
      mechanisms to identify and individually treat shock in the emergency setting. The
      non-invasive ultrasonic cardiac output monitoring (USCOM) device uses an
      ultrasound probe applied externally to the chest; however limitations exist with
      previous validation strategies. This study presents the in vitro validation of
      the USCOM device against calibrated flow sensors and compares user variability in
      simulated healthy and septic conditions. A validated mock circulation loop was
      used to simulate each condition with a range of cardiac outputs (2-10 l/min) and
      heart rates (50-95 bpm). Three users with varying degrees of experience using the
      USCOM device measured cardiac output and heart rate by placing the ultrasound
      probe on the mock aorta. Users were blinded to the condition, heart rate and
      cardiac output which were randomly generated. Results were reported as linear
      regression slope (beta). All users estimated heart rate in both conditions with
      reasonable accuracy (beta = 0.86-1.01), while cardiac output in the sepsis
      condition was estimated with great precision (beta = 1.03-1.04). Users generally
      overestimated the cardiac output in the healthy simulation (beta = 1.07-1.26) and
      reported greater difficulty estimating reduced cardiac output compared with
      higher values. Although there was some variability between users, particularly in
      the healthy condition (P < 0.01), all estimations were within a clinically
      acceptable range. In this study the USCOM provided a suitable measurement of
      cardiac output and heart rate when compared with our in vitro system. It is a
      promising technique to assist with the identification and treatment of shock. 

PMID- 25749978
TI  - Nucleocapsid Protein: A Desirable Target for Future Therapies Against HIV-1.
AB  - The currently available anti-HIV-1 therapeutics is highly beneficial to infected
      patients. However, clinical failures occur as a result of the ability of HIV-1 to
      rapidly mutate. One approach to overcome drug resistance is to target HIV-1
      proteins that are highly conserved among phylogenetically distant viral strains
      and currently not targeted by available therapies. In this respect, the
      nucleocapsid (NC) protein, a zinc finger protein, is particularly attractive, as
      it is highly conserved and plays a central role in virus replication, mainly by
      interacting with nucleic acids. The compelling rationale for considering NC as a
      viable drug target is illustrated by the fact that point mutants of this protein
      lead to noninfectious viruses and by the inability to select viruses resistant to
      a first generation of anti-NC drugs. In our review, we discuss the most relevant
      properties and functions of NC, as well as recent developments of small molecules
      targeting NC. Zinc ejectors show strong antiviral activity, but are endowed with
      a low therapeutic index due to their lack of specificity, which has resulted in
      toxicity. Currently, they are mainly being investigated for use as topical
      microbicides. Greater specificity may be achieved by using non-covalent NC
      inhibitors (NCIs) targeting the hydrophobic platform at the top of the zinc
      fingers or key nucleic acid partners of NC. Within the last few years, innovative
      methodologies have been developed to identify NCIs. Though the antiviral activity
      of the identified NCIs needs still to be improved, these compounds strongly
      support the druggability of NC and pave the way for future structure-based design
      and optimization of efficient NCIs. 

PMID- 25749979
TI  - Leukemia stem cells: the root of chronic myeloid leukemia.
AB  - Chronic myeloid leukemia (CML) is a clonal myeloproliferative disorder
      characterized by a chromosome translocation that generates the Bcr-Abl oncogene
      encoding a constitutive kinase activity. Despite remarkable success in
      controlling CML at chronic phase by Bcr-Abl tyrosine kinase inhibitors (TKIs), a
      significant proportion of CML patients treated with TKIs develop drug resistance
      due to the inability of TKIs to kill leukemia stem cells (LSCs) that are
      responsible for initiation, drug resistance, and relapse of CML. Therefore, there
      is an urgent need for more potent and safer therapies against leukemia stem cells
      for curing CML. A number of LSC-associated targets and corresponding signaling
      pathways, including CaMKII-gamma, a critical molecular switch for co-activating
      multiple LSC-associated signaling pathways, have been identified over the past
      decades and various small inhibitors targeting LSC are also under development.
      Increasing evidence shows that leukemia stem cells are the root of CML and
      targeting LSC may offer a curable treatment option for CML patients. This review
      summarizes the molecular biology of LSC and its-associated targets, and the
      potential clinical application in chronic myeloid leukemia. 

PMID- 25749981
TI  - Isolation and characterization of carotenoid cleavage dioxygenase 4 genes from
      different citrus species.
AB  - In plants, the carotenoid cleavage dioxygenase 4 (CCD4) could target on
      plastoglobules and cleave specific carotenoids, producing apocarotenoids and
      volatile compounds. These compounds are important for color and aroma formation
      in fruits and flowers. In this study, five CCD4 gene members (CCD4a, b, c, d, and
      e) were investigated in different citrus species including mandarin, pummelo, and
      sweet orange. Sequence analysis showed that the CCD4 genes from all the species
      examined exhibited extensive allelic variability (including SNPs and frame-shift
      mutations). Furthermore, the distribution of the CCD4 allelic mutation sites
      supported our previous hypothesis that the sweet orange originated from the
      hybridization of mandarin and pummelo. A derived cleaved amplified polymorphic
      sequence (dCAPs) marker was then successfully developed based on the allelic
      polymorphism of CCD4c, providing an ideal molecular marker for studying the
      genetic relationship between citrus species. Quantitative RT-PCR analysis
      identified differential expression patterns for the CCD4 genes in tissues/organs,
      and CCD4b was shown to have a high-level expression in citrus fruit flavedos
      (especially those with a deep orange-reddish color). HPLC-based detection of a
      key component (i.e., beta-citraurin) for orange-reddish flavedo formation in
      different citrus revealed a positive correlation between CCD4b expression levels
      and the presence of beta-citraurin, suggesting that CCD4b may be responsible for
      beta-citraurin biosynthesis in flavedo. In summary, this study not only
      reinforced the anticipated roles of CCD4 genes in flavedo color formation in
      citrus, but also provided new information about gene expression patterns, allelic
      polymorphism characteristics, and sequence variability for this gene subfamily.

PMID- 25749980
TI  - Current review of genetics of human obesity: from molecular mechanisms to an
      evolutionary perspective.
AB  - It is well-known that obesity is a complex multifactorial and heterogeneous
      condition with an important genetic component. Recently, major advances in
      obesity research emerged concerning the molecular mechanisms contributing to the
      obese condition. This review outlines several studies and data concerning the
      genetics and other important factors in the susceptibility risk to develop
      obesity. Based in the genetic etiology three main categories of obesity are
      considered: monogenic, syndromic, and common obesity. For the monogenic forms of
      obesity, the gene causing the phenotype is clearly identified, whereas for the
      common obesity the loci architecture underlying the phenotype is still being
      characterized. Given that, in this review we focus mainly in this obesity form,
      reviewing loci found until now by genome-wide association studies related with
      the susceptibility risk to develop obesity. Moreover, we also detail the obesity
      related loci identified in children and in different ethnic groups, trying to
      highlight the complexity of the genetics underlying the common obese phenotype.
      Importantly, we also focus in the evolutionary hypotheses that have been proposed
      trying to explain how natural selection favored the spread of genes that increase
      the risk for an obese phenotype and how this predisposition to obesity evolved.
      Other factors are important in the obesity condition, and thus, we also discuss
      the epigenetic mechanisms involved in the susceptibility and development of
      obesity. Covering all these topics we expect to provide a complete and recent
      perspective about the underlying mechanisms involved in the development and
      origin of obesity. Only with a full understanding of the factors and mechanisms
      contributing to obesity, it will be possible to provide and allow the development
      of new therapeutic approaches to this condition.

PMID- 25749983
TI  - Adequacy of lymph node yield and staging in rectal cancer should not be
      determined based on a minimum number of lymph nodes evaluated.

PMID- 25749984
TI  - Building a FP-CIT SPECT Brain Template Using a Posterization Approach.
AB  - Spatial affine registration of brain images to a common template is usually
      performed as a preprocessing step in intersubject and intrasubject comparison
      studies, computer-aided diagnosis, region of interest selection and brain
      segmentation in tomography. Nevertheless, it is not straightforward to build a
      template of [123I]FP-CIT SPECT brain images because they exhibit very low
      intensity values outside the striatum. In this work, we present a procedure to
      automatically build a [123I]FP-CIT SPECT template in the standard Montreal
      Neurological Institute (MNI) space. The proposed methodology consists of a head
      voxel selection using the Otsu's method, followed by a posterization of the
      source images to three different levels: background, head, and striatum.
      Analogously, we also design a posterized version of a brain image in the MNI
      space; subsequently, we perform a spatial affine registration of the posterized
      source images to this image. The intensity of the transformed images is
      normalized linearly, assuming that the histogram of the intensity values follows
      an alpha-stable distribution. Lastly, we build the [123I]FP-CIT SPECT template by
      means of the transformed and normalized images. The proposed methodology is a
      fully automatic procedure that has been shown to work accurately even when a high
      resolution magnetic resonance image for each subject is not available.

PMID- 25749982
TI  - Autoimmune hepatitis.
AB  - Autoimmune hepatitis is a chronic liver disease putatively caused by loss of
      tolerance to hepatocyte-specific autoantigens. It is characterized by female
      predilection, elevated aminotransferase levels, autoantibodies, increased gamma
      globulin or IgG levels and biopsy evidence of interface hepatitis. It is
      currently divided into types 1 and 2, based on expression of autoantibodies.
      Autoantigenic epitopes have been identified only for the less frequent type 2.
      Although autoimmune hepatitis occurs in childhood, this review focuses on disease
      in adults. In the absence of pathognomonic biomarkers, diagnosis requires
      consideration of clinical, biochemical, serological and histological features,
      which have been codified into validated diagnostic scoring systems. Since many
      features also occur in other chronic liver diseases, these scoring systems aid
      evaluation of the differential diagnosis. New practice guidelines have redefined
      criteria for remission to include complete biochemical and histological
      normalization on immunosuppressive therapy. Immunosuppression is most often
      successful using prednisone or prednisolone and azathioprine; however, the
      combination of budesonide and azathioprine for non-cirrhotic patients offers
      distinct advantages. Patients failing standard immunosuppression are candidates
      for alternative immunosuppressive regimens, yet none of the options has been
      studied in a randomized, controlled trial. Overlap syndromes with either primary
      sclerosing cholangitis or primary biliary cirrhosis occur in a minority. Liver
      transplantation represents a life-saving option for patients presenting with
      acute liver failure, severely decompensated cirrhosis or hepatocellular
      carcinoma. Transplant recipients are at risk for recurrent autoimmune hepatitis
      in the allograft, and de novo disease may occur in patients transplanted for
      other indications. Patients transplanted for AIH are also at risk for recurrent
      or de novo inflammatory bowel disease. Progress in our understanding of the
      immunopathogenesis should lead to identification of specific diagnostic and
      prognostic biomarkers and new therapeutic strategies.

PMID- 25749985
TI  - Segmentation of the Cerebellar Peduncles Using a Random Forest Classifier and a
      Multi-object Geometric Deformable Model: Application to Spinocerebellar Ataxia
      Type 6.
AB  - The cerebellar peduncles, comprising the superior cerebellar peduncles (SCPs),
      the middle cerebellar peduncle (MCP), and the inferior cerebellar peduncles
      (ICPs), are white matter tracts that connect the cerebellum to other parts of the
      central nervous system. Methods for automatic segmentation and quantification of
      the cerebellar peduncles are needed for objectively and efficiently studying
      their structure and function. Diffusion tensor imaging (DTI) provides key
      information to support this goal, but it remains challenging because the tensors
      change dramatically in the decussation of the SCPs (dSCP), the region where the
      SCPs cross. This paper presents an automatic method for segmenting the cerebellar
      peduncles, including the dSCP. The method uses volumetric segmentation concepts
      based on extracted DTI features. The dSCP and noncrossing portions of the
      peduncles are modeled as separate objects, and are initially classified using a
      random forest classifier together with the DTI features. To obtain geometrically
      correct results, a multi-object geometric deformable model is used to refine the
      random forest classification. The method was evaluated using a leave-one-out
      cross-validation on five control subjects and four patients with spinocerebellar
      ataxia type 6 (SCA6). It was then used to evaluate group differences in the
      peduncles in a population of 32 controls and 11 SCA6 patients. In the SCA6 group,
      we have observed significant decreases in the volumes of the dSCP and the ICPs
      and significant increases in the mean diffusivity in the noncrossing SCPs, the
      MCP, and the ICPs. These results are consistent with a degeneration of the
      cerebellar peduncles in SCA6 patients. 

PMID- 25749986
TI  - Safety, tolerability, and pharmacokinetics of single and multiple doses of
      intravenous cixutumumab (IMC-A12), an inhibitor of the insulin-like growth factor
      I receptor, administered weekly or every 2 weeks in patients with advanced solid
      tumors.
AB  - BACKGROUND: Type 1 insulin-like growth factor receptor (IGF-IR) signaling is
      often dysregulated in cancer. Cixutumumab, a fully human IgG1 monoclonal
      antibody, blocks IGF-IR and inhibits downstream signaling. The current study
      determined the recommended dose, safety, and pharmacokinetic (PK) profile of
      weekly or every-2-week dosing of cixutumumab. PATIENTS AND METHODS: Two open
      label, multicenter phase I studies evaluated weekly (3-15 mg/kg) or every-2-weeks
      (6-15 mg/kg) dosing of cixutumumab in patients with advanced solid tumors. Serial
      blood samples for PK were collected up to 168-336 h (day 8-15) following the
      first administration of cixutumumab. Efficacy was evaluated as best overall tumor
      response. RESULTS: A total of 24 and 16 patients were enrolled in the weekly and
      every-2-week dosing studies, respectively. Treatment-emergent adverse events
      (>=10%) included hyperglycemia, fatigue, anemia, nausea, and vomiting. Severe
      adverse events (AE) were infrequent; one serious AE (grade 3 electrocardiogram QT
      prolongation) was deemed possibly cixutumumab-related (10 mg/kg every-2-weeks).
      One death occurred due to disease progression (6 mg/kg weekly cohort). Maximum
      serum concentrations increased with dose. A maximum tolerated dose was not
      identified; pre-determined target serum minimum concentrations (60 MUg/mL) were
      achieved with >=6 mg/kg weekly and >=10 mg/kg every-2-week dosing. Cixutumumab
      terminal elimination half-life is approximately a week (individual range, t1/2 =
      4.58-9.33 days based upon 10 mg/kg every 2 weeks). Overall, stable disease was
      achieved in 25% of all patients. CONCLUSIONS: Cixutumumab was associated with
      favorable safety and PK profiles. A dosing regimen of 10 mg/kg every 2 weeks was
      recommended for subsequent disease-focused clinical trials.

PMID- 25749987
TI  - A correlation between decreased parathyroid alpha-Klotho and fibroblast growth
      factor receptor 1 expression with pathological category and parathyroid gland
      volume in dialysis patients.
AB  - OBJECTIVES: The objective of this study was to investigate alpha-Klotho and
      fibroblast growth factor receptor 1 (FGFR1) expression in hyperplastic
      parathyroid glands, as well as their role in the development of renal
      hyperparathyroidism. METHODS: Hyperplastic parathyroid glands (n = 90) were
      obtained from 24 patients who received parathyroidectomy due to secondary renal
      hyperparathyroidism. Normal parathyroid tissue was obtained from glands (n = 6)
      that were inadvertently removed, in conjunction with thyroidectomy, from patients
      with thyroid carcinoma. The expression of alpha-Klotho and FGFR1 in the
      parathyroid tissue was detected using immunohistochemical staining. RESULTS: The
      expression of alpha-Klotho and FGFR1 was significantly reduced in the
      hyperplastic parathyroid tissue compared to that in the normal parathyroid
      tissue. The expression of alpha-Klotho decreased further with increasing
      parathyroid pathology. A significant positive correlation was observed between
      alpha-Klotho and FGFR1 (r = 0.38, P < 0.01). FGFR1 (r = -0.21, P < 0.05) and
      alpha-Klotho (r = -0.42, P < 0.01) were negatively correlated with the volume of
      the hyperplastic parathyroid tissue. CONCLUSION: The expression of alpha-Klotho
      and FGFR1 decreases in the parathyroid glands of dialysis patients with secondary
      hyperparathyroidism, and this decrease may play an important role in the
      pathogenesis of secondary renal hyperparathyroidism.

PMID- 25749988
TI  - Association of renal function, estimated by four equations, with coronary artery
      disease.
AB  - OBJECTIVE: Individuals with impaired renal function are at increased risk of
      coronary artery disease (CAD). CAD is also associated with an increased
      likelihood of having chronic kidney disease (CKD). In the present study, we
      sought to determine the association between impaired renal function with CAD
      presence and CAD severity based on four different estimated glomerular filtration
      rate (eGFR) equations. METHODS: We estimated GFR values using four equations:
      modification of diet in renal disease (MDRD), Cockcroft-Gault (C-G), chronic
      kidney disease epidemiology (CKD-Epi), and Mayo Quadratic. Three hundred and
      fifty-six CAD patients were classified by the number of stenotic coronary
      arteries occluded >50%, while the CAD severity was categorized based on the
      number of involved coronary arteries determined to be healthy, single- and multi
      vessel disease. RESULTS: The mean values of eGFR calculated by CKD-Epi, MDRD,
      Mayo, and C-G equations were 77.44, 71.34, 96.33, and 89.49 mL/min/1.73 m(2)
      respectively. Based on these equations, the prevalence of eGFR <60 mL/min/1.73
      m(2) among the patients with significant CAD was 41.5, 45.2, 50, and 42.9%,
      respectively. eGFR values calculated by four formulas were significantly higher
      in healthy subjects than those with single-vessel disease (p < 0.001, p = 0.004,
      p = 0.003, and p = 0.028, respectively). Prediction of CAD severity was
      statistically significant for men but not women. After controlling for the
      confounding effects of other covariates, three of the equations were
      independently related to significant CAD: CKD-Epi (p = 0.004, beta = 0.969), MDRD
      (p = 0.003, beta = 0.965), and C-G (p = 0.021, beta = 0.978). CONCLUSION: The
      present study established that accurate eGFR equations commonly used still
      accurate to determine the association of the impaired renal function with CAD
      presence and extent.

PMID- 25749989
TI  - Maintaining the accuracy of the (60)Co calibration service at the ARPANSA post
      source replacement in 2010.
AB  - The Australian Radiation Protection and Nuclear Safety Agency (ARPANSA) maintains
      a (60)Co teletherapy source primarily for the calibration of therapy dosemeters.
      The source and encapsulating head were replaced in early 2010 with an Eldorado 78
      head and new (60)Co source. In this article we present the results of ongoing
      accuracy and stability measurements since the replacement. A number of formal and
      informal indirect comparisons have been carried out with laboratories holding
      primary and secondary standards for (60)Co. ARPANSA chambers have also been
      calibrated at international primary standard laboratories allowing comparison of
      calibration coefficients and thus (60)Co absorbed dose standards. (60)Co
      calibration coefficients supplied by manufacturers of chambers were compared to
      those measured at the ARPANSA when this calibration was traceable to a primary
      standard. ARPANSA also participates in an annual international mailed dosimetry
      audit conducted by the International Atomic Energy Agency. The results thus far
      demonstrate that the absorbed doses to water delivered by the new ARPANSA (60)Co
      source are consistent with international doses within the stated uncertainties. 

PMID- 25749990
TI  - Interactome analysis reveals that FAM161A, deficient in recessive retinitis
      pigmentosa, is a component of the Golgi-centrosomal network.
AB  - Defects in FAM161A, a protein of unknown function localized at the cilium of
      retinal photoreceptor cells, cause retinitis pigmentosa, a form of hereditary
      blindness. By using different fragments of this protein as baits to screen cDNA
      libraries of human and bovine retinas, we defined a yeast two-hybrid-based
      FAM161A interactome, identifying 53 bona fide partners. In addition to
      statistically significant enrichment in ciliary proteins, as expected, this
      interactome revealed a substantial bias towards proteins from the Golgi
      apparatus, the centrosome and the microtubule network. Validation of interaction
      with key partners by co-immunoprecipitation and proximity ligation assay
      confirmed that FAM161A is a member of the recently recognized Golgi-centrosomal
      interactome, a network of proteins interconnecting Golgi maintenance,
      intracellular transport and centrosome organization. Notable FAM161A interactors
      included AKAP9, FIP3, GOLGA3, KIFC3, KLC2, PDE4DIP, NIN and TRIP11. Furthermore,
      analysis of FAM161A localization during the cell cycle revealed that this protein
      followed the centrosome during all stages of mitosis, likely reflecting a
      specific compartmentalization related to its role at the ciliary basal body
      during the G0 phase. Altogether, these findings suggest that FAM161A's activities
      are probably not limited to ciliary tasks but also extend to more general
      cellular functions, highlighting possible novel mechanisms for the molecular
      pathology of retinal disease. 

PMID- 25749992
TI  - Three-dimensional spheroid culture of human umbilical cord mesenchymal stem cells
      promotes cell yield and stemness maintenance.
AB  - Mesenchymal stem cell (MSC) transplantation is a promising treatment of many
      diseases. However, conventional techniques with cells being cultured as a
      monolayer result in slow cell proliferation and insufficient yield to meet
      clinical demands. Three-dimensional (3D) culture systems are gaining attention
      with regard to recreating a complex microenvironment and to understanding the
      conditions experienced by cells. Our aim is to establish a novel 3D system for
      the culture of human umbilical cord MSCs (hUC-MSCs) within a real 3D
      microenvironment but with no digestion or passaging. Primary hUC-MSCs were
      isolated and grown in serum-free medium (SFM) on a suspension Rocker system. Cell
      characteristics including proliferation, phenotype and multipotency were
      recorded. The therapeutic effects of 3D-cultured hUC-MSCs on carbon tetrachloride
      (CCl4)-induced acute liver failure in mouse models were examined. In the 3D
      Rocker system, hUC-MSCs formed spheroids in SFM and maintained high viability and
      active proliferation. Compared with monolayer culture, the 3D-culture system
      yielded more hUC-MSCs cells within the same volume. The spheroids expressed
      higher levels of stem cell markers and displayed stronger multipotency. After
      transplantation into mouse, 3D hUC-MSCs significantly promoted the secretion of
      interferon-gamma and interleukin-6 but inhibited that of tumor necrosis factor
      alpha, thereby alleviating liver necrosis and promoting regeneration following
      CCl4 injury. The 3D culture of hUC-MSCs thus promotes cell yield and stemness
      maintenance and represents a promising strategy for hUC-MSCs expansion on an
      industrial scale with great potential for cell therapy and biotechnology.

PMID- 25749993
TI  - Deviance detection in auditory subcortical structures: what can we learn from
      neurochemistry and neural connectivity?
AB  - A remarkable ability of animals that is critical for survival is to detect and
      respond to to unexpected stimuli in an ever-changing world. Auditory neurons that
      show stimulus-specific adaptation (SSA), i.e., a decrease in their response to
      frequently occurring stimuli while maintaining responsiveness when different
      stimuli are presented, might participate in the coding of deviance occurrence.
      Traditionally, deviance detection is measured by the mismatch negativity (MMN)
      potential in studies of evoked local field potentials. We present a review of the
      state-of-the-art of SSA in auditory subcortical nuclei, i.e., the inferior
      colliculus and medial geniculate body of the thalamus, and link the differential
      receptor distribution and neural connectivity of those regions in which extreme
      SSA has been found. Furthermore, we review both SSA and MMN-like responses in
      auditory and non-auditory areas that exhibit multimodal sensitivities that we
      suggest conform to a distributed network encoding for deviance detection. The
      understanding of the neurochemistry and response similarities across these
      different regions will contribute to a better understanding of the neural
      mechanism underlying deviance detection. 

PMID- 25749991
TI  - Combined gene/cell therapies provide long-term and pervasive rescue of multiple
      pathological symptoms in a murine model of globoid cell leukodystrophy.
AB  - Globoid cell leukodystrophy (GLD) is a lysosomal storage disease caused by
      deficient activity of beta-galactocerebrosidase (GALC). The infantile forms
      manifest with rapid and progressive central and peripheral demyelination, which
      represent a major hurdle for any treatment approach. We demonstrate here that
      neonatal lentiviral vector-mediated intracerebral gene therapy (IC GT) or
      transplantation of GALC-overexpressing neural stem cells (NSC) synergize with
      bone marrow transplant (BMT) providing dramatic extension of lifespan and global
      clinical-pathological rescue in a relevant GLD murine model. We show that timely
      and long-lasting delivery of functional GALC in affected tissues ensured by the
      exclusive complementary mode of action of the treatments underlies the
      outstanding benefit. In particular, the contribution of neural stem cell
      transplantation and IC GT during the early asymptomatic stage of the disease is
      instrumental to enhance long-term advantage upon BMT. We clarify the input of
      central nervous system, peripheral nervous system and periphery to the disease,
      and the relative contribution of treatments to the final therapeutic outcome,
      with important implications for treatment strategies to be tried in human
      patients. This study gives proof-of-concept of efficacy, tolerability and
      clinical relevance of the combined gene/cell therapies proposed here, which may
      constitute a feasible and effective therapeutic opportunity for children affected
      by GLD. 

PMID- 25749994
TI  - Establishing the Psychometric Properties of the Comprehensive Ethos Towards
      Wellness Questionnaire in a Norwegian Population.
AB  - AIM: to replicate and establish the psychometric properties of the 74-item
      comprehensive Ethos Towards Wellness Questionnaire in a healthy Norwegian
      population in terms of content and construct validity as well as homogeneity and
      stability reliability. METHOD: A questionnaire with a methodological and
      developmental design was sent on two occasions to 214 healthy middle-aged
      participants and processed in two phases. RESULTS: The three life context and the
      ethos indexes at ordinal scale level showed an overall satisfactory construct
      validity (communalities > 0.30, factor loadings > 0.30, and factor total variance
      > 50%). On two occasions 4 weeks apart, reliability in terms of homogeneity
      (Cronbach's alpha > .70) and stability (intraclass correlation coefficient >
      0.70) were also considered satisfactory for the same four indexes. CONCLUSIONS:
      This newly developed and possibly only questionnaire that focuses on "grasping
      the big human picture," based on both philosophical reasoning and empirical
      recommendations of wellness, was found to be valid and reliable in the screening
      and follow-up of wellness and ethos in a healthy Norwegian population.

PMID- 25749995
TI  - Pilot Study: Use of Mindfulness, Self-Compassion, and Yoga Practices With Low
      Income and/or Uninsured Patients With Depression and/or Anxiety.
AB  - PURPOSE: This pilot study was conducted to determine the effectiveness of
      mindfulness practices, including self-compassion and yoga, on depression and/or
      anxiety in uninsured and/or low-income patients. DESIGN: The design was repeated
      measures with one group. METHOD: Patients received 8 weeks of mindfulness
      training including self-compassion and yoga. Depression and anxiety symptoms,
      self-compassion, and psychological well-being were measured four times. FINDINGS:
      Interventions were effective in helping uninsured and low-income patients reduce
      depression and/or anxiety symptoms. CONCLUSION: This study may have implications
      for a cost-effective treatment for these disorders. The findings from this study
      can provide useful information to health care providers.

PMID- 25749996
TI  - Complete genome sequence of a new recombinant echovirus 25 strain isolated from a
      neonatal patient with hand, foot, and mouth disease complicated by encephalitis
      in Beijing, China.
AB  - Although human echovirus 25 (E-25), a type of the enterovirus B species, is
      implicated in aseptic meningitis, information on its gene structure, evolution,
      and virulence are limited. We report here the complete genome sequence of a novel
      recombinant E-25 strain (E25/2010/CHN/BJ) isolated from a neonate with hand,
      foot, and mouth disease complicated by encephalitis in Beijing, China in 2010.
      The complete viral genome consists of 7429 nucleotides (nts), including a 6585-nt
      open reading frame. Phylogenetic dendrogram based on VP1 gene regions revealed
      that this strain belonged to subgroup D4, which contains the other E-25 strains
      isolated from China in recent years. The difference in the amino acid sites
      (P130S, K/T135I) of the VP1 region may affect its immunogenicity. SimPlot and
      Bootscan analyses suggested that E25/2010/CHN/BJ is a recombination result of E
      25 and Coxsackievirus B3 (CVB-3) strains. Our results would facilitate the study
      of the origin, evolution, and molecular epidemiology of E-25. 

PMID- 25749997
TI  - Fluorometric RdRp assay with self-priming RNA.
AB  - There is an outmost need for the identification of specific antiviral compounds.
      Current antivirals lack specificity, making them susceptible to off-target
      effects, and highlighting importance of development of assays to discover
      antivirals targeting viral specific proteins. Previous studies for identification
      of inhibitors of RNA-dependent RNA polymerase (RdRp) mostly relied on radioactive
      methods. This study describes a fluorometric approach to assess in vitro activity
      of viral RdRp for drug screening. Using readily available DNA- and RNA-specific
      fluorophores, we determined an optimum fluorometric approach that could be used
      in antiviral discovery specifically for RNA viruses by targeting RdRp. Here, we
      show that double-stranded RNA could be successfully distinguished from single
      stranded RNA. In addition, we provide a strategy based on self-priming RNA to
      assess RdRp activity. 

PMID- 25749998
TI  - Pulmonary embolism and pulmonary hypertension: two issues often neglected in
      cardiology.

PMID- 25750000
TI  - Influence of Hyphal Inoculum potential on the Competitive Success of Fungi
      Colonizing Wood.
AB  - The relative amounts of hyphal inoculum in forest soils may determine the
      capacity for fungi to compete with and replace early colonizers of wood in ground
      contact. Our aim in this study was to test the flexibility of priority effects
      (colonization timing) by varying the timing of inoculum introduction (i.e.,
      precolonization) and amount of inoculum (i.e., inoculum potential). We controlled
      these variables in soil-block microcosms using fungi with known competitive
      outcomes in similar conditions, tracking isolate-specific fungal biomass, and
      residue physiochemistry over time. In the precolonization trial (experiment I), a
      brown rot fungus Gloeophyllum trabeum was given 1, 3, or 5 weeks to precolonize
      wood blocks (oak, birch, pine, and spruce) prior the introduction of a white rot
      fungus, Irpex lacteus, a more aggressive colonizer in this set-up. In the
      inoculum potential trial (experiment II), the fungi were inoculated
      simultaneously, but with eightfold higher brown rot inoculum than that of
      experiment I. As expected, longer precolonization duration increased the chance
      for the less-competitive brown rot fungus to outcompete its white rot opponent.
      Higher brown rot fungal inoculum outside of the wood matrix also resulted in
      competitive success for the brown rot isolate in most cases. These temporal
      shifts in fungal dominance were detectable in a 'community snapshot' as isolate
      specific quantitative PCR, but also as functionally-relevant consequences of wood
      rot type, including carbohydrate depolymerization and pH. These results from a
      controlled system reinforce fungal-fungal interaction and suggest that relative
      inoculum availability beyond the wood matrix (i.e., soils) might regulate the
      duration of priority effects and shift the functional trajectory of wood
      decomposition. 

PMID- 25750001
TI  - The Hemodynamic Response of Spreading Depolarization Observed by Near Infrared
      Spectroscopy After Aneurysmal Subarachnoid Hemorrhage.
AB  - BACKGROUND: Electrocorticography (ECoG) in brain-injured patients allows to
      detect spreading depolarization, a potential mechanism of secondary ischemia.
      Here, we describe the relationship of spreading depolarization with changes in
      cerebral hemodynamics using a brain tissue probe applying near infrared
      spectroscopy (NIRS). METHODS: Simultaneous ECoG and NIRS monitoring was performed
      in a patient with severe aneurysmal subarachnoid hemorrhage. Changes in cerebral
      blood oxygenation and regional cerebral blood volume were studied before and
      after the occurrence of spreading depolarization. Cerebral blood flow
      measurements were performed daily using an indocyanine green dye dilution mode.
      RESULTS: Single events of spreading depolarizations demonstrated with transient
      hyperoxic responses and increase in cerebral blood volume. On the other hand,
      temporal clusters of recurrent spreading depolarizations were associated with
      prolonged hypoxic responses and decrease in cerebral blood volume. Cerebral blood
      flow measurements showed higher values before compared to after onset of
      spreading depolarization (33.7 +/- 8.4 vs. 24.2 +/- 4.5 ml/100 g/min).
      CONCLUSIONS: The findings suggest that NIRS monitoring in the cerebral white
      matter might reflect the hemodynamic signature of spreading depolarization
      detected by ECoG recordings. This is of potential interest for the further
      development of both neuromonitoring methods.

PMID- 25750005
TI  - Exploring primary school headteachers' perspectives on the barriers and
      facilitators of preventing childhood obesity.
AB  - BACKGROUND: Headteachers of primary schools in England are a crucial partner for
      childhood obesity prevention. Understanding how this works in practice is limited
      by their views being underrepresented or missing from the evidence base. The aim
      of this study was to explore primary school headteachers' perspectives on
      childhood obesity and the perceived barriers and facilitators of prevention.
      METHODS: A qualitative study with a purposive sample of 14 primary school
      headteachers from the Yorkshire and Humber region of England was conducted. Semi
      structured interviews were audio-taped, transcribed and analysed using an
      inductive thematic approach. RESULTS: An extensive range of barriers and
      facilitators emerged within four key themes; understanding childhood obesity,
      primary school setting, the role of parents and external partners. A lack of
      knowledge, awareness and skills to deal with the sensitivity and complexity of
      childhood obesity across all school stakeholders presents the most significant
      barrier to effective action. CONCLUSIONS: Headteachers recognize primary schools
      are a crucial setting for childhood obesity prevention; however their school's
      often do not have the capability, capacity and confidence to make a meaningful
      and sustainable impact. To increase headteachers' ability and desire to prevent
      childhood obesity, schools require specialist and tailored training, resources
      and support from external partners such as public health teams and school nursing
      services.

PMID- 25750006
TI  - Stop regain: a pilot psychological intervention for bariatric patients
      experiencing weight regain.
AB  - BACKGROUND: A subset of bariatric patients fails to achieve or maintain long-term
      successful weight loss. Psychological and behavioral factors contributing to poor
      long-term outcomes include decreased adherence to surgical eating guidelines,
      life stressors that derail weight maintenance, unhealthy eating patterns, and
      substance use. OBJECTIVES: A 6-week pilot group behavioral intervention utilizing
      techniques of cognitive behavioral therapy (CBT) and dialectical behavior therapy
      (DBT) was developed to treat bariatric patients experiencing weight regain.
      SETTING: Patients were treated at a large Midwestern academic medical center.
      METHODS: Twenty-eight patients (93% female, 100% Caucasian) with a mean age of 53
      and a mean BMI of 35.6 had regained an average of 17 kg or 37% of the weight lost
      after initially successful Roux-en-Y gastric bypass (RYGB). All patients
      completed the Structured Clinical Interview for DSM-IV-TR (SCID I) modules
      assessing mood and substance dependence, and completed a series of questionnaires
      before and after group treatment, with weekly assessment of depressive symptoms,
      binge eating, and alcohol use. Results were analyzed utilizing repeated measures
      ANOVA. RESULTS: Weight decreased during the intervention by an average of 1.6 +/-
      2.38 kg (p <= 0.01). Level of depressive symptoms improved for treatment
      completers (p <= 0.01). Food records indicated that grazing patterns decreased (p
      <= 0.01) and subjective binge eating episodes decreased (p <= 0.03). CONCLUSIONS:
      A 6-week pilot group behavioral intervention demonstrated an ability to help
      patients reverse their pattern of weight regain. Tailored behavioral
      interventions may be a useful treatment to enhance maintenance of long-term
      weight loss.

PMID- 25750007
TI  - A comparison of aortic valve replacement via an anterior right minithoracotomy
      with standard sternotomy: a propensity score analysis of 492 patients.
AB  - OBJECTIVES: Right anterior minithoracotomy with central arterial cannulation is
      our preferred technique of minimally invasive aortic valve replacement (AVR). We
      compared perioperative outcomes with this technique to those via sternotomy.
      METHODS: Between March 1999 and December 2013, 492 patients underwent isolated
      AVR via either sternotomy (SAVR, n = 198) or minimally invasive right anterior
      thoracotomy (MIAVR, n = 294) in our institution. Univariate comparisons between
      groups were made to evaluate overall outcomes and adverse events. To control
      treatment selection bias, propensity scores were constructed from core patient
      characteristics. A propensity score-stratified analysis of outcome and adverse
      events was then performed. RESULTS: Overall mortality was 2.5 and 1.0% in the
      SAVR and MIAVR groups, respectively. Hospital and ICU stays were shorter, there
      was less intraoperative blood product usage, and fewer wound infections in the
      MIAVR group. There were no differences in other adverse events, including
      strokes. The composite end-point of alive and adverse event-free was
      significantly more common in the MIAVR group (83 vs 74%, P = 0.002). After
      adjusting for the propensity score, hospital and ICU stays remained shorter and
      intraoperative blood product usage remained less in the MIAVR group. There was no
      difference in mortality, stroke or other adverse events between groups.
      CONCLUSION: Minimally invasive AVR via an anterior right thoracotomy with
      predominately central cannulation can be performed with morbidity and mortality
      similar to that of a sternotomy approach. There appear to be advantages to this
      minimally invasive approach when compared with sternotomy in terms of less
      intraoperative blood product usage, lower wound infection rates and decreased
      hospital stays. If mortality and the occurrence of adverse events are taken
      together, MIAVR may be associated with better outcomes. As minimally invasive AVR
      becomes more common, further long-term follow-up is needed and a prospective
      multicentre randomized trial would be warranted.

PMID- 25750008
TI  - The effects of hydrogen gas inhalation during ex vivo lung perfusion on donor
      lungs obtained after cardiac death.
AB  - OBJECTIVES: Lung transplantation is a well-established treatment of end-stage
      lung disease; however, it is limited by a shortage of donor lungs. To overcome
      this problem, donation after cardiac death (DCD) and ex vivo lung perfusion
      (EVLP) are being widely investigated. In this study, the effect of hydrogen gas,
      a known antioxidant, was investigated on a DCD lung model during EVLP. METHODS:
      Ten pigs were randomized into either a control (n = 5) or a hydrogen group (n =
      5). After fibrillation by electric shock, no further treatment was administered
      in order to induce warm ischaemic injury for 1 h. The lungs were then procured,
      followed by 4 h of EVLP. During EVLP, the lungs were ventilated with room air in
      the control group, and with 2% hydrogen gas in the hydrogen group. Oxygen
      capacity (OC), pulmonary vascular resistance (PVR) and peak airway pressure (PAP)
      were measured every hour, and the expressions of interleukin-1 beta (IL-1beta),
      IL-6 (IL-6), IL-8 (IL-8) and tumour necrosis factor-alpha (TNF-alpha) were
      evaluated in lung tissue after EVLP. Pathological evaluations were performed
      using lung injury severity (LIS) scores and the wet/dry ratio was also measured.
      RESULTS: The OC in the hydrogen group was higher than in the control group, but
      the difference was not statistically significant (P = 0.0862). PVR (P = 0.0111)
      and PAP (P = 0.0189) were statistically significantly lower in the hydrogen
      group. Compared with the control group, the hydrogen group had a statistically
      significantly lower expression of IL-1beta (P = 0.0317), IL-6 (P = 0.0159), IL-8
      (P = 0.0195) and TNF-alpha (P = 0.0159). The LIS scores (P = 0.0358) and wet/dry
      ratios (P = 0.040) were also significantly lower in the hydrogen group.
      CONCLUSIONS: Hydrogen gas inhalation during EVLP improved the function of DCD
      lungs, which may increase the utilization of DCD lungs.

PMID- 25750009
TI  - Bicuspid aortic valve disease and ascending aortic aneurysm: should an aortic
      root replacement be mandatory??.
AB  - OBJECTIVES: The higher risk of adverse aortic events in patients with bicuspid
      aortic valve (BAV) disease and ascending aorta aneurysm is known, but the
      management of moderate aortic root dilatation in younger patients is a
      controversial issue. The aim of the study was to compare survival in patients
      with or without root replacement. METHODS: We reviewed 166 consecutive patients
      with BAV disease and concomitant ascending aorta aneurysm (mean ascending aorta
      diameter: 51.4 +/- 7.2 mm) undergoing cardiac surgery from 1994 to 2010. A total
      of 77 patients underwent Bentall procedure (90.9% male, mean age: 55.7 +/- 12.7
      years, Bentall group), whereas the remaining 89 patients underwent aortic valve
      replacement with supracoronary ascending aorta replacement (SAAR 71.9% male, mean
      age: 60.5 +/- 11.2 years, SAAR group, P = 0.002). The preoperative mean diameter
      of the root was 44.0 +/- 7.2 mm in the Bentall, and 38.5 +/- 4.8 mm in the SAAR
      group (P < 0.0001). RESULTS: In-hospital mortality was 2.6% in the Bentall, and
      2.3% in the SAAR groups. Overall survival was 84 and 81% in the Bentall (median
      follow-up: 105 months) versus 89 and 88% in the SAAR (median follow-up: 73
      months) groups at 10 and 15 years (P = 0.36), respectively. The mean
      cardiopulmonary bypass (CPB) time was 201 +/- 56 min and 174 +/- 58 min (P =
      0.0016), the mean cross-clamp time 156 +/- 42 min and 132 +/- 38 min (P = 0.0008)
      in the Bentall and SAAR groups, respectively. Four sudden deaths have occurred in
      the Bentall group and in 2 in the SAAR group. Progressive dilatation of the
      aortic root in the SAAR group was not significat (postoperative mean diameter:
      36.3 +/- 4.4 mm). Neither subgroup of patients in the SAAR with preoperative
      moderate dilatation of aortic root had significat aortic dilatation at the mean
      follow-up of 73 +/- 39 months (preoperative diameter: 43.5 +/- 2.3 mm versus
      postoperative: 39.1 +/- 4.2 mm). One patient in Bentall and 1 in the SAAR groups
      were reoperated for tubular graft infection. CONCLUSIONS: In patients with BAV
      disease, ascending aorta aneurysm and moderate dilatation of the root, the
      significat reduction of CPB and cross-clamp times, the stability of the residual
      root at long term and the low risk of adverse aortic events associated with SAAR
      compared with the Bentall procedure have led us to consider the isolated aortic
      valve replacement with supracoronary aorta replacement an alternative strategy to
      the Bentall procedure, especially in high-risk and older patients.

PMID- 25750011
TI  - Application of exercise transcutaneous oxygen pressure measurements for detection
      of proximal lower extremity arterial disease: a case report.
AB  - Proximal claudication is secondary to ischemia caused by peripheral artery
      disease (PAD), whereas proximal pseudo-claudication is secondary to other disease
      processes such as hip arthritis, spinal stenosis, neuropathy, and so forth. The
      differentiation between the two can be challenging. Exercise transcutaneous
      oxygen pressure measurement (exercise-TcPO2) allows noninvasive detection of flow
      reducing lesions in the proximal arteries and tributaries of the lower extremity
      arterial tree. We present the first case report in the United States using an
      exercise-TcPO2 algorithm. A 71-year-old diabetic patient with proximal left-sided
      and right-calf claudication with indeterminate ankle-brachial indices underwent
      an exercise-TcPO2 study before and after endovascular intervention. Four TcPO2
      probes were placed: one at chest level (reference probe), one on each buttock,
      and one on the symptomatic calf. The Delta from Resting Oxygen Pressure (DROP)
      index was calculated at each probe site using a previously validated protocol.
      Proximal left- and right-calf ischemia were confirmed by the initial exercise
      TcPO2, and, after endovascular treatment of the left iliac artery lesion,
      improvements in proximal exercise-TcPO2 values were found. These data suggest
      that exercise-TcPO2 can be useful in PAD evaluation in patients with non
      compressible arteries and/or proximal claudication.

PMID- 25750010
TI  - European multicentre experience with the sutureless Perceval valve: clinical and
      haemodynamic outcomes up to 5 years in over 700 patients.
AB  - OBJECTIVES: This report summarizes the 5-year clinical and haemodynamic data from
      three prospective, European multicentre trials with the Perceval sutureless
      aortic valve. METHODS: From April 2007 to August 2012, 731 consecutive patients
      (mean age: 78.5 years; 68.1% females; mean logistic EuroSCORE 10.9%) underwent
      AVR with the Perceval valve in 25 European centres. Isolated AVR was performed in
      498 (68.1%) patients. A minimally invasive approach was performed in 189 (25.9%)
      cases. The cumulative follow-up was 729 patients-years. RESULTS: In isolated AVR,
      mean cross-clamp and cardiopulmonary bypass times were 30.8 and 50.8 min in full
      sternotomy, and 37.6 and 64.4 min in the minimally invasive approach,
      respectively. Early cardiac-related deaths occurred in 1.9%. Overall survival
      rates at 1 and 5 years were 92.1 and 74.7%, respectively. Major paravalvular leak
      occurred in 1.4% and 1% at early and late follow-up, respectively. Significant
      improvement in clinical status was observed postoperatively in the majority of
      patients. Mean and peak gradients decreased from 42.9 and 74.0 mmHg
      preoperatively, to 7.8 and 16 mmHg at the 3-year follow-up. LV mass decreased
      from 254.5 to 177.4 g at 3 years. CONCLUSIONS: This European multicentre
      experience, with the largest cohort of patients with sutureless valves to date,
      shows excellent clinical and haemodynamic results that remain stable even up to
      the 5-year follow-up. Even in this elderly patient cohort with 40% octogenarians,
      both early and late mortality rates were very low. There were no valve
      migrations, structural valve degeneration or valve thrombosis in the follow-up.
      The sutureless technique is a promising alternative to biological aortic valve
      replacement.

PMID- 25750012
TI  - Venous thromboembolism in systemic autoimmune diseases: A narrative review with
      emphasis on primary systemic vasculitides.
AB  - Venous thromboembolism (VTE) is a prevalent multifactorial health condition
      associated with significant morbidity and mortality. Population-based
      epidemiological studies have revealed an association between systemic autoimmune
      diseases and deep venous thrombosis (DVT)/VTE. The etiopathogenesis of increased
      risk of VTE in systemic autoimmune diseases is not entirely clear but multiple
      contributors have been explored, especially in the context of systemic
      inflammation and disordered thrombogenesis. Epidemiologic data on increased risk
      of VTE in patients with primary systemic vasculitides (PSV) have accumulated in
      recent years and some of these studies suggest the increased risk while patients
      have active diseases. This could lead us to hypothesize that venous vascular
      inflammation has a role to play in this phenomenon, but this is unproven. The
      role of immunosuppressive agents in modulating the risk of VTE in patients with
      PSV is not yet clear except for Behcet's disease, where most of the studies are
      retrospective. Sensitizing physicians to this complication has implications for
      prevention and optimal management of patients with these complex diseases. This
      review will focus on the epidemiology and available evidence regarding
      pathogenesis, and will attempt to summarize the best available data regarding
      evaluation and treatment of these patients. 

PMID- 25750013
TI  - The effect of intrinsic and acquired resistances on chemotherapy effectiveness.
AB  - Although chemotherapy is one of the most common treatments for cancer, it can be
      only partially successful. Drug resistance is the main cause of the failure of
      chemotherapy. In this work, we present a mathematical model to study the impact
      of both intrinsic (preexisting) and acquired (induced by the drugs) resistances
      on chemotherapy effectiveness. Our simulations show that intrinsic resistance
      could be as dangerous as acquired resistance. In particular, our simulations
      suggest that tumors composed by even a small fraction of intrinsically resistant
      cells may lead to an unsuccessful therapy very quickly. Our results emphasize the
      importance of monitoring both intrinsic and acquired resistances during treatment
      in order to succeed and the importance of doing more experimental and genetic
      research in order to develop a pretreatment clinical test to avoid intrinsic
      resistance. 

PMID- 25750014
TI  - Assessment of the impact of chlorophyll derivatives to control parasites in
      aquatic ecosystems.
AB  - Several research groups have studied new biopesticides which are less toxic to
      the environment and capable of controlling the vectors of parasitic diseases,
      especially in aquatic ecosystems. Pest control by photodynamic substances is an
      alternative to chemical or other measures, with chlorophyll and its derivatives
      as the most studied substances supported by their easy availability and low
      production costs. The impact of chlorophyll derivatives on four different
      species, a small crustacean (Daphnia similis), a unicellular alga (Euglena
      gracilis) and two species of fish (Astyanax bimaculatus and Cyprynus carpio) were
      tested under short-term conditions. In addition, the effects of long-term
      exposure were evaluated in D. similis and E. gracilis. In short-term tests,
      mortality of D. similis (EC50 = 7.75 mg/L) was most strongly affected by
      chlorophyllin, followed by E. gracilis (EC50 = 12.73 mg/L). The fish species
      showed a greater resistance documented by their EC50 values of 17.58 and 29.96
      mg/L in C. carpio and A. bimaculatus, respectively. A risk quotient is calculated
      by dividing an estimate of exposure by an estimate of effect. It indicated that
      chlorophyll derivatives can be applied in nature to control the vectors of
      parasitic diseases under short-term conditions, but long-term exposure requires
      new formulations. 

PMID- 25750015
TI  - Effects of eutrophic seawater and temperature on the physiology and morphology of
      Hypnea musciformis J. V. Lamouroux (Gigartinales, Rhodophyta).
AB  - As both food and source of a kappa-carrageenan, Hypnea musciformis represents a
      species of great economic interest. It also synthesizes substances with
      antiviral, anti-helminthic and anti-inflammatory potential and shows promise for
      use as a bioindicator of cadmium. In this study, we investigated the combined
      effects of seawater from three urbanized areas (area 1: natural runoff, NRA; area
      2: urbanized runoff and sewage with treatment, RTA; area 3: urbanized runoff and
      untreated sewage, RUS) and three different temperatures (15, 25 and 30  degrees
      C) on the growth rate, photosynthetic efficiency, photosynthetic pigments and
      cell morphology of H. musciformis. After 4 days (96 h) of culture, the biomass of
      H. musciformis showed differences that fluctuated among the areas and temperature
      treatments. Specifically, the specimens cultivated in 35  degrees C had low
      values of ETRmax, alpha(ETR), beta(ETR), and Fv/Fm photosynthetic parameters, as
      well as changes in cell morphology, with reduction in photosynthetic pigments and
      drastic reduction in growth rates. When combined with the extreme temperatures,
      high concentrations of ammonium ion in seawater effluent caused an inhibition of
      photosynthetic activity, as well as significant variation in chlorophyll a and
      carotenoid contents. As observed by light microscopy, the synergism between
      different temperatures and pollutants found in eutrophic waters caused changes in
      cellular morphology with increased cell wall thickening and decreased floridean
      starch grains. H. musciformis also showed important changes in physiological
      response to each factor independently, as well as changes resulting from the
      synergistic interaction of these factors combined. Therefore, we can conclude
      that extreme temperature combined with the effect of eutrophic waters, especially
      RUS, caused distinct morphological and physiological changes in the red alga H.
      musciformis.

PMID- 25750016
TI  - Tissue microcirculation measured by vascular occlusion test during anesthesia
      induction.
AB  - Tissue microcirculation measured by vascular occlusion test is impaired during
      septic shock. However, it has not been investigated extensively during anesthesia
      induction. The aim of the study is to evaluate tissue microcirculation during
      anesthesia induction. We hypothesized that during anesthesia induction, tissue
      microcirculation measured by vascular occlusion test might be enhanced with
      peripheral vasodilation during anesthesia induction. We conducted a prospective
      observational study of 50 adult patients undergoing cardiac surgery. During
      anesthesia induction, we measured and analyzed tissue oxygen saturation, vascular
      occlusion test, cerebral oximetry, forearm-minus-fingertip skin temperature
      gradients and hemodynamic data in order to evaluate microcirculation as related
      to alterations in peripheral vasodilation as reflected by increased Tforearm
      finger thermal gradients. During anesthesia induction, recovery slope during
      vascular occlusion test and cerebral oxygen saturation increased from 4.0 (1.5)
      to 4.7 (1.3) % s(-1) (p = 0.02) and 64.0 (10.2) to 74.2 (9.2) % (p < 0.001),
      respectively. Forearm-minus-fingertip skin temperature gradients decreased from
      1.9 (2.9) to -1.4 (2.2)  degrees C (p < 0.001). There was an inverse correlation
      between changes in the skin temperature gradients and changes in cerebral
      oximetry (r = 0.33; p = 0.02). During anesthesia induction, blood pressure and
      forearm-minus-fingertip skin temperature gradients decrease while cerebral
      oximetry and vascular occlusion test recovery slope increase. These findings
      suggest that anesthesia induction increases tissue microcirculation with
      peripheral vasodilation. 

PMID- 25750017
TI  - Pulse transit time shows vascular changes caused by propofol in children.
AB  - Pulse transit time (PTT) is the time that it takes for the arterial pulse
      pressure wave to travel from the aortic valve to the periphery. It is a simple
      noninvasive technique for evaluating vascular changes. This study investigated
      the vascular changes by propofol during the induction of anesthesia in pediatric
      patients with the measuring of PTT. Without premedication, 2 mg/kg of propofol
      was administered intravenously with monitoring of electrocardiogram (ECG) and
      photoplethysmograph (PPG) in 20 pediatric patients aged 3-7 years. The ECG and
      PPG data were obtained for 1 min before propofol injection (baseline PTT) and 2
      min after administration of propofol in the operating room. The PTT was defined
      as the time interval from the R-wave on the ECG to the maximum upslope of the
      corresponding PPG. The PTT was calculated off-line after collecting the data. The
      mean baseline PTT was 166.2 +/- 25.9 ms and maximum PTT after propofol injection
      was 315.9 +/- 64.9 ms (the interval between injection and the peak was 17.3 +/-
      7.6 s). The PTT after the peak changed variously; most of the patients showed no
      plateau; the PTT decreased progressively after the peak. The PTT after propofol
      administration prolonged in short time and rapidly recovered toward to the
      baseline values in pediatric patients. In conclusion, the baseline PTT in
      children is shorter comparing with adults and the vasodilatory effect of propofol
      on the vessels as described by the PTT was rapid and the recovery was faster,
      although the response to propofol was more varied than in adults.

PMID- 25750018
TI  - Computational study of missense mutations in phenylalanine hydroxylase.
AB  - Hyperphenylalaninemia (HPA) is one of the most common metabolic disorders. HPA,
      which is transmitted by an autosomal recessive mode of inheritance, is caused by
      mutations of the phenylalanine hydroxylase gene. Most mutations are missense and
      lead to reduced protein stability and/or impaired catalytic function. The impact
      of such mutations varies, ranging from classical phenylketonuria (PKU), mild PKU,
      to non-PKU HPA phenotypes. Despite the fact that HPA is a monogenic disease,
      clinical data show that one PKU genotype can be associated with more in vivo
      phenotypes, which indicates the role of other (still unknown) factors. To better
      understand the phenotype-genotype relationships, we analyzed computationally the
      impact of missense mutations in homozygotes stored in the BIOPKU database. A
      total of 34 selected homozygous genotypes was divided into two main groups
      according to their phenotypes: (A) genotypes leading to non-PKU HPA or combined
      phenotype non-PKU HPA/mild PKU and (B) genotypes leading to classical PKU, mild
      PKU or combined phenotype mild PKU/classical PKU. Combining in silico analysis
      and molecular dynamics simulations (in total 3 MUs) we described the structural
      impact of the mutations, which allowed us to separate 32 out of 34 mutations
      between groups A and B. Testing the simulation conditions revealed that the
      outcome of mutant simulations can be modulated by the ionic strength. We also
      employed programs SNPs3D, Polyphen-2, and SIFT but based on the predictions
      performed we were not able to discriminate mutations with mild and severe PKU
      phenotypes. 

PMID- 25750019
TI  - Analysis of the flexibility and stability of the structure of magainin in a
      bilayer, and in aqueous and nonaqueous solutions using molecular dynamics
      simulations.
AB  - The precise mode of the antimicrobial activity of Magainin (Mag)-an antimicrobial
      peptide (AMP)-is still unclear. In this study, the conformation of Mag was
      characterized in water, and in a methanol and lipid bilayer [palmitoyl
      oleoylphosphatidylcholine (POPC)] using a molecular dynamics (MD) simulation
      technique. To describe the role conformation plays in Mag function, the global
      conformational differences within three systems were studied. Through analysis of
      the resulting configuration ensembles, the differences in the three systems, such
      as overall flexibility and average secondary structure, were studied. It is
      suggested that these differences may be important enough to influence
      interactions with lipid biomembranes, thereby influencing key properties such as
      penetration into cell membrane and stability. 

PMID- 25750020
TI  - Electronic structure of modelized vs. real carbon-chain containing organometallic
      dinuclear complexes: similarities and differences.
AB  - DFT calculations were carried out on the homo- and hetero-bimetallic model wires
      [(eta(5)-C5H5)(dpe)Fe-C=C-C6H4-C=C-Fe(dpe)(eta(5)-C5H5)] (1'), [(eta(7)
      C7H7)(dpe)Mo-C=C-C6H4-C=C-Mo(dpe)(eta(7)-C7H7)] (2'), and [(eta(5)-C5H5)(dpe)Fe
      C=C-C6H4-C=C-Mo(dpe)(eta(7)-C7H7)] (3') used to tentatively mimic [(eta(5)
      C5Me5)(dppe)Fe-C=C-C6H4-C=C-Fe(dppe)(eta(5)-C5Me5)] (1), [(eta(7)-C7H7)(dppe)Mo
      C=C-C6H4-C=C-Mo(dppe)(eta(7)-C7H7)] (2), and [(eta(5)-C5Me5)(dppe)Fe-C=C-C6H4-C=C
      Mo(dppe)(eta(7)-C7H7)] (3), respectively in order to analyze the similarities and
      the differences between models and real compounds previously theoretically and
      experimentally studied, with respect to their molecular structures and
      properties. A comparison of the metrical data computed for the models and the
      real systems shows some slight discrepancy between the metal-ancillary ligand
      distances - shorter distances are observed in the formers - but comparable metal
      Calpha and Calpha-Cbeta distances. Incidentally, distances computed for the model
      molecules match more closely those measured experimentally. Replacement of a dppe
      ligand tethered to the metal centers by a dpe group does not much alter the
      electronic properties. Therefore, overall, data obtained for the Mo2 models 2'
      compare rather well with those computed for the real systems 2. Larger alteration
      is noticed when Cp* is substituted by Cp, even if the general trends observed for
      the real iron species 1 and 3 are kept overall for the iron models 1' and 3'.
      Indeed, the smaller electron-donor properties of Cp affect somewhat the nodal
      properties of the HOMOs (less metallic character) and increase the HOMO-LUMO gaps
      and the ionization potentials. Despite this, similarities between models and real
      compounds largely overtake differences. It is shown that calculations on models
      provide quite acceptable results.

PMID- 25750021
TI  - Computational design of small phenothiazine dyes for dye-sensitized solar cells
      by functionalizations affecting the thiophene unit.
AB  - We present a computational density functional theory study of the potential to
      improve the solar absorbance of small organic dyes featuring a phenothiazine
      donor and an acceptor moiety that combines a thiophene unit and a cyanoacrylic
      group. We consider different conjugation orders and functional groups on and
      around the thiophene unit, including electron-donating and electron-withdrawing
      moieties (H, F, CH3, CF3, and CN). We predict that by combining change of
      conjugation order and functionalization with electron withdrawing CN groups, it
      must be possible to decrease the excitation energy by up to 60 % vs. the parent
      dye (which would correspond to a redshift of the absorption peak maximum from 450
      nm to 726 nm), effectively enabling red light absorption with small dyes. The
      contraction of the band gap is mostly due to the stabilization of the LUMO (by up
      to 1.8 eV), so that-in spite of the kinetic redundancy of the parent dye with
      respect to the conduction-band minimum of TiO2-care must be taken to ensure
      efficient injection when using the dyes in dye-sensitized solar cells. By
      studying 50 dyes, of which 44 are new dyes that are studied for the first time in
      this work, we identify parameters (such as charges, dihedral angles between donor
      and acceptor groups, bond length alternation) which can serve as predictors of
      the band gap. We find that bond length alternation or dihedral angles are not
      good predictors, while the charge on the thiophene unit is. 

PMID- 25750022
TI  - The effect of ligands on the thermal stability of sulfotransferases: a molecular
      dynamics simulation study.
AB  - Human cytosolic sulfotransferases (hSULTs) are important phase II metabolic
      enzymes. They catalyze transfer of the sulfuryl-group (-SO3) from 3'
      phosphoadenosine 5'-phosphosulfate (PAPS) to the hydroxyl or primary amine
      moieties of a large number of endogenous and xenobiotic substrates. Broad
      selectivity and specificity of binding and activity within the sulfortransferases
      family could be detected by thermal denaturation assays, which have been made
      more and more suitable for high throughput screening based on recent technical
      advances. Here molecular dynamics simulations were used to explore the effect of
      the cofactor (PAPS) and substrate (LCA) on the thermal stability of the enzyme.
      It was found that the apo-enzyme unfolded fastest upon heating. The holo-enzyme
      with bound substrate LCA unfolded slowest. This thermo-denaturation order is
      consistent with that observed in experiments. Further it was found that the
      cofactor and substrate will pronouncedly increase the thermal stability of the
      active pocket regions that interact directly with the ligands. In addition,
      cofactor and substrate show noticeable synergy effect on the thermal stability of
      the enzyme. 

PMID- 25750023
TI  - New insights into the insertion reactions of germylenoid H2GeLiF with RH (R = F,
      OH, NH2).
AB  - In the present work, a new pathway of the insertion reactions of H2GeLiF with RH
      (R = F, OH, NH2) was investigated using DFT B3LYP and QCISD methods. The
      geometries of the stationary points on the potential energy surfaces in the
      reactions were optimized at the B3LYP/6-311 + G (d, p) level and then the single
      point energies were calculated at the QCISD/6-311++G (d, p) level. The calculated
      results indicated that the initial step of all the reactions is the isomerization
      of the p-complex structure to a three-membered-ring structure. After
      isomerization, the insertion reactions of three-membered-ring H2GeLiF with RH (R
      = F, OH, NH2) take place. The QCISD/6-311++G (d, p)//B3LYP/6-311 + G (d, p)
      calculated potential energy barriers of the three reactions were 89.77, 137.40,
      and 167.45 kJ mol(-1), respectively. Under the same situation, the insertion
      reactions should occur easily in the following order H-F > H-OH > H-NH2. Compared
      with the direct insertion reactions of H2GeLiF with RH (R = F, OH, NH2), the two
      step insertions have lower activation barriers and should be more favorable. 

PMID- 25750024
TI  - Theoretical insight on atmospheric chemistry of HFE-365mcf3: reactions with OH
      radicals, atmospheric lifetime, and fate of alkoxy radicals
      (CF3CF2CH(O(*))OCH3/CF3CF2CH2OCH2O(*)).
AB  - In the present work, theoretical study on the mechanism and kinetics of the gas
      phase reactions of CF3CF2CH2OCH3 (HFE-365mcf3) with the OH radicals have been
      performed using meta-hybrid modern density functional M06-2X in conjunction with
      6-31+G(d,p) basis set. Reaction profiles for OH-initiated hydrogen abstraction
      are modeled including the formation of pre-reactive and post-reactive complexes
      at entrance and exit channels. Our calculations reveal that hydrogen abstraction
      from the -CH2 group is thermodynamically more facile than that from the -CH3
      group. This is further ascertained by the calculated C-H bond dissociation energy
      of CF3CF2CH2OCH3 molecule. The rate constants of the titled reactions are
      computed over the temperature range of 250-450 K. The calculated rate constant
      value at 298 K is found to be in reasonable agreement with the experimental
      results. The atmospheric life time of HFE-365mcf3 is estimated to be 42 days. The
      atmospheric fate of the alkoxy radicals, CF3CF2CH(O(*))OCH3 and CF3CF2CH2OCH2O(*)
      are also investigated for the first time using the same level of theory. Out of
      three plausible decomposition channels, our results clearly point out that
      reaction with O2 is the dominant atmospheric sink for the decomposition of
      CF3CF2CH(O(*))OCH3 radical in the atmosphere. 

PMID- 25750025
TI  - BagMOOV: A novel ensemble for heart disease prediction bootstrap aggregation with
      multi-objective optimized voting.
AB  - Conventional clinical decision support systems are based on individual
      classifiers or simple combination of these classifiers which tend to show
      moderate performance. This research paper presents a novel classifier ensemble
      framework based on enhanced bagging approach with multi-objective weighted voting
      scheme for prediction and analysis of heart disease. The proposed model overcomes
      the limitations of conventional performance by utilizing an ensemble of five
      heterogeneous classifiers: Naive Bayes, linear regression, quadratic discriminant
      analysis, instance based learner and support vector machines. Five different
      datasets are used for experimentation, evaluation and validation. The datasets
      are obtained from publicly available data repositories. Effectiveness of the
      proposed ensemble is investigated by comparison of results with several
      classifiers. Prediction results of the proposed ensemble model are assessed by
      ten fold cross validation and ANOVA statistics. The experimental evaluation shows
      that the proposed framework deals with all type of attributes and achieved high
      diagnosis accuracy of 84.16 %, 93.29 % sensitivity, 96.70 % specificity, and
      82.15 % f-measure. The f-ratio higher than f-critical and p value less than 0.05
      for 95 % confidence interval indicate that the results are extremely
      statistically significant for most of the datasets. 

PMID- 25750026
TI  - Retroperitoneal perirenal myxoid liposarcoma.
AB  - Liposarcomas are neoplasms of mesodermic origin, are derived from adipose tissue
      and represent <1% of all malignant tumours. Primary liposarcomas of the kidney
      are very rare. Here, we present the cases of two patients diagnosed with
      retroperitoneal perirenal myxoid liposarcoma. The patients were diagnosed via
      imaging, which in both cases revealed a huge right retroperitoneal tumour mass
      compressing the abdominal organs and large blood vessels. Surgical intervention
      consisting of en bloc resection of the tumour and the right kidney was performed
      using a transperitoneal approach. Three years after the surgery, both patients
      presented local recurrence, for which they underwent chemotherapy. Liposarcomas
      with renal origin are rare clinical entities with a high rate of malignancy and a
      poor prognosis. Because the use of chemotherapy and radiotherapy in the treatment
      of such liposarcomas is controversial, the treatment of choice is wide surgical
      resection with clean margins. 

PMID- 25750027
TI  - Society for Maternal Fetal Medicine 2015 Annual Pregnancy Meeting supplemental
      episode 5: Post-Meeting Round-Up (Part 1 of 3).

PMID- 25750028
TI  - Autocrine DNA fragmentation of intra-epithelial lymphocytes (IELs) in mouse small
      intestine.
AB  - Intraepithelial lymphocytes (IELs) are present in the intestinal epithelium.
      Mechanisms of IELs for the protection of villi from foreign antigens and from
      infections by micro-organisms have not been sufficiently explained. Although more
      than 70% of mouse duodenal and jejunal IELs bear gammadeltaTCR (gammadeltaIELs),
      the functions of gammadeltaIELs are little investigated. We stimulate
      gammadeltaIELs by anti-CD3 monoclonal antibody (mAb) injection. The mAb activates
      gammadeltaIELs to release Granzyme B (GrB) into the spaces surrounding the
      gammadeltaIELs and intestinal villous epithelial cells (IECs). Released GrB
      induces DNA fragmentation in IECs independently of Perforin (Pfn). IECs
      immediately repair their fragmented DNA. Activated IELs reduce their cell size,
      remain for some time in the epithelium after the activation and are ultimately
      eliminated without leaving the site. We focus our attention on the response of
      IELs to the released GrB present in the gap surrounding IELs, after activation,
      in order to examine whether the released GrB has a similar effect on IELs to that
      observed on IECs in our previous studies. DNA fragmentation is also induced in
      IELs together with the repair of fragmented DNA thereafter. The time-kinetics of
      both events were found to be identical to those observed in IECs. DNA
      fragmentation in IELs is Pfn-independent. Here, we present Pfn-independent
      "autocrine DNA fragmentation" in IELs and the repair of fragmented DNA in IELs
      and discuss their biological significance. Autocrine DNA fragmentation has never
      been reported to date in vivo.

PMID- 25750029
TI  - Risperidone Attenuates Modified Stress-Re-stress Paradigm-Induced Mitochondrial
      Dysfunction and Apoptosis in Rats Exhibiting Post-traumatic Stress Disorder-Like
      Symptoms.
AB  - Mitochondria play a significant role in the pathophysiology of post-traumatic
      stress disorder (PTSD). Risperidone and paroxetine were evaluated for their
      effect on mitochondrial dysfunction and mitochondria-dependent apoptosis in
      discrete brain regions in modified stress re-stress (SRS) animal model of PTSD.
      Male rats were subjected to stress protocol of 2 h restraint and 20 min forced
      swim followed by halothane anesthesia on day 2 (D-2). Thereafter, rats were
      exposed to re-stress (forced swim) on D-8 and at 6-day intervals on D-14, D-20, D
      26, and D-32. The rats were treated with risperidone (0.01, 0.1, and 1.0 mg/kg
      p.o.) and paroxetine (10.0 mg/kg p.o.) from D-8 to D-32. Risperidone at median
      dose and paroxetine ameliorated modified SRS-induced depressive-like symptom
      (increase in immobility period) in forced swim, anxiety-like behavior (decrease
      in percentage of open arm entries and time spent) in elevated plus maze and
      cognitive deficits (loss in spatial recognition memory) in Y-maze tests on D-32.
      Risperidone, but not paroxetine, attenuated modified SRS-induced decreases in
      plasma corticosterone levels. Risperidone ameliorated increase in the activity of
      mitochondrial respiratory complex (I, II, IV, and V), decreases in the levels of
      mitochondrial membrane potential, cytochrome-C and caspase-9 in the hippocampus,
      hypothalamus, pre-frontal cortex, and amygdala. However, both drugs attenuated
      modified SRS-induced increase in the number of apoptotic cells and caspase-3
      levels in all the brain regions indicating anti-apoptotic activity of these
      drugs. Hence, these results suggest that anti-apoptotic activity could be a
      common mechanism for anti-PTSD-like effect irrespective of the pathways of
      apoptosis in the modified SRS model.

PMID- 25750030
TI  - Mutational analysis to identify the residues essential for the inhibition of N
      acetyl glutamate kinase of Corynebacterium glutamicum.
AB  - N-acetyl glutamate kinase (NAGK) is a key enzyme in the synthesis of L-arginine
      that is inhibited by its end product L-arginine in Corynebacterium glutamicum (C.
      glutamicum). In this study, the potential binding sites of arginine and the
      residues essential for its inhibition were identified by homology modeling,
      inhibitor docking, and site-directed mutagenesis. The allosteric inhibition of
      NAGK was successfully alleviated by a mutation, as determined through analysis of
      mutant enzymes, which were overexpressed in vivo in C. glutamicum ATCC14067.
      Analysis of the mutant enzymes and docking analysis demonstrated that residue W23
      positions an arginine molecule, and the interaction between arginine and residues
      L282, L283, and T284 may play an important role in the remote inhibitory process.
      Based on the results of the docking analysis of the effective mutants, we propose
      a linkage mechanism for the remote allosteric regulation of NAGK activity, in
      which residue R209 may play an essential role. In this study, the structure of
      the arginine-binding site of C. glutamicum NAGK (CgNAGK) was successfully
      predicted and the roles of the relevant residues were identified, providing new
      insight into the allosteric regulation of CgNAGK activity and a solid platform
      for the future construction of an optimized L-arginine producing strain. 

PMID- 25750031
TI  - A high-efficiency recombineering system with PCR-based ssDNA in Bacillus subtilis
      mediated by the native phage recombinase GP35.
AB  - Bacillus subtilis and its closely related species are important strains for
      industry, agriculture, and medicine. However, it is difficult to perform genetic
      manipulations using the endogenous recombination machinery. In many bacteria,
      phage recombineering systems have been employed to improve recombineering
      frequencies. To date, an efficient phage recombineering system for B. subtilis
      has not been reported. Here, we, for the first time, identified that GP35 from
      the native phage SPP1 exhibited a high recombination activity in B. subtilis. On
      this basis, we developed a high-efficiency GP35-meditated recombineering system.
      Taking single-stranded DNA (ssDNA) as a recombineering substrate, ten
      recombinases from diverse sources were investigated in B. subtilis W168. GP35
      showed the highest recombineering frequency (1.71 +/- 0.15 * 10(-1)). Besides
      targeting the purine nucleoside phosphorylase gene (deoD), we also demonstrated
      the utility of GP35 and Beta from Escherichia coli lambda phage by deleting the
      alpha-amylase gene (amyE) and uracil phosphoribosyltransferase gene (upp). In all
      three genetic loci, GP35 exhibited a higher frequency than Beta. Moreover, a
      phylogenetic tree comparing the kinship of different recombinase hosts with B.
      subtilis was constructed, and the relationship between the recombineering
      frequency and the kinship of the host was further analyzed. The results suggested
      that closer kinship to B. subtilis resulted in higher frequency in B. subtilis.
      In conclusion, the recombinase from native phage or prophage can significantly
      promote the genetic recombineering frequency in its host, providing an effective
      genetic tool for constructing genetically engineered strains and investigating
      bacterial physiology.

PMID- 25750032
TI  - Imaging Chronic Tuberculous Lesions Using Sodium [(18)F]Fluoride Positron
      Emission Tomography in Mice.
AB  - PURPOSE: Calcification is a hallmark of chronic tuberculosis (TB) in humans,
      often noted years to decades (after the initial infection) on chest radiography,
      but not visualized well with traditional positron emission tomography (PET). We
      hypothesized that sodium [(18)F]fluoride (Na[(18)F]F) PET could be used to detect
      microcalcifications in a chronically Mycobacterium tuberculosis-infected murine
      model. PROCEDURES: C3HeB/FeJ mice, which develop necrotic and hypoxic TB lesions,
      were aerosol-infected with M. tuberculosis and imaged with Na[(18)F]F PET.
      RESULTS: Pulmonary TB lesions from chronically infected mice demonstrated
      significantly higher Na[(18)F]F uptake compared with acutely infected or
      uninfected animals (P < 0.01), while no differences were noted in the blood or
      bone compartments (P > 0.08). Ex vivo biodistribution studies confirmed the
      imaging findings, and tissue histology demonstrated microcalcifications in TB
      lesions from chronically infected mice, which has not been demonstrated
      previously in a murine model. CONCLUSION: Na[(18)F]F PET can be used for the
      detection of chronic TB lesions and could prove to be a useful noninvasive
      biomarker for TB studies.

PMID- 25750033
TI  - Effects of freshwater leaching on potential bioavailability of heavy metals in
      tidal flat soils.
AB  - Leaching experiments were conducted to investigate the effects of desalination
      levels and sediment depths on potential bioavailability of heavy metal (Cd, Cr,
      Cu, Fe, Mn, Ni, Pb, and Zn) in tidal flat soils. The data showed that both the
      desalination levels (p < 0.001) and soil depths (p < 0.001) had significant
      effects on the concentrations of acid-volatile sulfide (AVS). AVS concentrations
      generally exhibited increasing trends with an increase in depth and decreasing
      trends with enhanced desalination levels. The desalination levels had significant
      (p < 0.05) effects on the concentrations of simultaneously extracted metal (SEM;
      Cd, Cr, Cu, Fe, Mn, Pb, and Zn). Moreover, the concentrations of SEM (Cd, Cr, Cu,
      Fe, Mn, Pb, and Zn) generally tended to decrease with an increase in the
      desalination level. The desalination treatment significantly reduced the ratios
      of SEM/AVS compared with control. However, the ratios of SEM/AVS increased with
      enhanced desalination levels in treatments. Results reveal that low desalination
      treatment is better for reducing toxicity to benthic organisms than high
      desalination treatment. Since these reclaimed tidal flats with low desalinisation
      are suitable for saline water aquaculture, transforming the present land use of
      reclaimed tidal flats from fresh water aquaculture into saline water aquaculture
      may reduce health risk of heavy metals remained in sediments. These results will
      also contribute to our understanding of the dynamic behavior of heavy metals in
      the reclamation of tidal flats during leaching and the role of the ratio of
      SEM/AVS predictions on assessing the ecological risks of reclaimed tidal flats. 

PMID- 25750034
TI  - Identification of suitable endogenous controls for gene and miRNA expression
      studies in irradiated prostate cancer cells.
AB  - This study aimed to to evaluate the stability of commonly used endogenous control
      genes for messenger RNA (mRNA) (N = 16) and miRNAs (N = 3) expression studies in
      prostate cell lines following irradiation. The stability of endogenous control
      genes expression in irradiated (6 Gy) versus unirradiated controls was quantified
      using NormFinder and coefficient of variation analyses. HPRT1 and 18S were
      identified as most and least stable endogenous controls, respectively, for mRNA
      expression studies in irradiated prostate cells. SNORD48 and miR16 miRNA
      endogenous controls tested were associated with low coefficient of variations
      following irradiation (6 Gy). This study highlights that commonly used endogenous
      controls can be responsive to radiation and validation is required prior to
      gene/miRNAs expression studies.

PMID- 25750035
TI  - Erratum to: Endothelin-1 overexpression: a potential biomarker of unfavorable
      prognosis in non-metastatic muscle-invasive bladder cancer.

PMID- 25750036
TI  - Mutation-introduced dimerization of receptor tyrosine kinases: from protein
      structure aberrations to carcinogenesis.
AB  - Cancer is the greatest challenge to human health in our era. Perturbations of
      receptor tyrosine kinase (RTK) function contribute to a large chunk of cancer
      etiology. Current evidence supports that mutations in RTKs mediate receptor
      dimerization and result in ligand-independent kinase activity and tumorigenesis,
      indicating that mutation-introduced receptor dimerization is a critical component
      of oncogenesis RTK mutations. However, there are no specialized reviews of this
      important principle. In the current review, we discuss the physiological and
      harmless RTK function and subsequently examine mutation-introduced dimerization
      of RTKs and the role of these mutations in tumorigenesis. We also summarize the
      protein structure characteristics that are important for dimerization and
      introduce research methods and tools to predict and validate the existence of
      oncogenic mutations introduced by dimerization in RTKs. 

PMID- 25750037
TI  - Role of Yes-associated protein 1 in gliomas: pathologic and therapeutic aspects.
AB  - The activation of proline-rich phosphoprotein Yes-associated protein 1 (YAP1)
      possesses a possible link between stem/progenitor cells, organ size, and cancer.
      YAP1 has been indicated as an oncoprotein, and overexpression of YAP1 is reported
      in many human brain tumors, including infiltrating gliomas. During normal brain
      development, the neurofibromatosis 2 (NF2) protein suppresses YAP1 activity in
      neural progenitor cells to promote guidepost cell differentiation, but loss of
      NF2 causes elevating YAP1 activity in midline neural progenitors, which disrupts
      guidepost formation. Overexpression of endogenous CD44 (cancer stem cell marker)
      promotes phosphorylation/inactivation of NF2, and upregulates YAP1 expression and
      leads to cancer cell resistance in glioblastoma. The hippo pathway is also
      related to the YAP1 action. However, the mechanism of YAP1 action in glioma is
      still far from clear understanding. Advances in clinical management based on an
      improved understanding of the function of YAP1 may help to serve as a molecular
      target in glioma therapeutics. Knockdown of YAP1 by shRNA technology has been
      shown to reduce glioma in vitro; however, clinical implications are still under
      investigation. YAP1 can be used as a diagnostic marker for gliomas to monitor the
      disease status and may help to evaluate its treatment effects. More functional
      experiments are needed to support the direct roles of YAP1 on gliomas at
      molecular and cellular levels. 

PMID- 25750038
TI  - Appropriate time for selective biliary cannulation by trainees during ERCP--a
      randomized trial.
AB  - BACKGROUND AND STUDY AIM: The allocation of sufficient time for trainees to
      attempt cannulation is necessary for learning and to ensure success with
      endoscopic retrograde cholangiopancreatography (ERCP) training. However, it is
      important to balance the benefit to trainee practice against the potential risks
      to patients. The appropriate time for attempted cannulation by trainees remains
      unclear. PATIENTS AND METHODS: Three different time limits (5, 10, 15 minutes)
      were set for cannulation attempts made by four trainees in patients with native
      papilla undergoing ERCP. Patients were randomly assigned to the 5-, 10-, or 15
      minute groups in a 1:1:1 ratio. Rectal indomethacin was used in high-risk
      patients. The primary outcome was successful cannulation within the allocated
      time. Secondary outcomes included performance scores, overall success rate, and
      post-ERCP pancreatitis (PEP). RESULTS: A total of 256 patients were randomly
      assigned to the 5-minute (n = 84), 10-minute (n = 86), or 15-minute (n = 86)
      groups. Patients' baseline characteristics were comparable. Success rates for
      selective bile duct cannulation by trainees were 43.8 %, 75.0 %, and 71.8 % in
      the 5-, 10-, and 15-minute groups, respectively (P < 0.001). Trainees' self
      reported performance scores and video assessment by an independent reviewer were
      comparable between the 10- and 15-minute groups, which were higher than the 5
      minute group (both P  < 0.001). Trainers took over the cannulation procedure when
      trainees did not succeed within the allocated time. There was no significant
      difference in the overall success rates in cannulation between the three groups.
      No differences were noted in the use of rectal indomethacin and overall
      complication rates. Four patients in each group developed PEP (P = 0.996).
      CONCLUSION: A time of 10 minutes was considered to be appropriate for trainees to
      attempt cannulation, with acceptable cannulation success rates and complications.
      TRIAL REGISTRATION: ClinicalTrials.gov number (NCT01851226).

PMID- 25750039
TI  - Age-Related Changes in Pharyngeal Lumen Size: A Retrospective MRI Analysis.
AB  - Age-related loss of muscle bulk and strength (sarcopenia) is often cited as a
      potential mechanism underlying age-related changes in swallowing. Our goal was to
      explore this phenomenon in the pharynx, specifically, by measuring pharyngeal
      wall thickness and pharyngeal lumen area in a sample of young versus older women.
      MRI scans of the neck were retrospectively reviewed from 60 women equally
      stratified into three age groups (20s, 60s, 70+). Four de-identified slices were
      extracted per scan for randomized, blinded analysis: one mid-sagittal and three
      axial slices were selected at the anterior inferior border of C2 and C3, and at
      the pit of the vallecula. Pixel-based measures of pharyngeal wall thickness and
      pharyngeal lumen area were completed using ImageJ and then converted to metric
      units. Measures of pharyngeal wall thickness and pharyngeal lumen area were
      compared between age groups with one-way ANOVAs using Sidak adjustments for post
      hoc pairwise comparisons. A significant main effect for age was observed across
      all variables whereby pharyngeal wall thickness decreased and pharyngeal lumen
      area increased with advancing age. Pairwise comparisons revealed significant
      differences between 20s versus 70+ for all variables and 20s versus 60s for all
      variables except those measured at C2. Effect sizes ranged from 0.54 to 1.34.
      Consistent with existing sacropenia literature, the pharyngeal muscles appear to
      atrophy with age and consequently, the size of the pharyngeal lumen increases. 

PMID- 25750040
TI  - Adjuvant sorafenib therapy in patients with resected hepatocellular carcinoma:
      evaluation of predictive factors.
AB  - Currently there is no predictor for survival after adjuvant sorafenib in patients
      with hepatocellular carcinoma (HCC) who have undergone curative resection. Thirty
      eight patients who underwent curative resection of HCC received adjuvant
      sorafenib therapy between August 2009 and March 2012. Clinicopathological
      parameters including patient factors, tumor factors, liver background, and
      inflammatory factors (before surgery and dynamic changes after sorafenib therapy)
      were evaluated to identify predictors for overall survival (OS) and recurrence
      free survival (RFS). The recurrence rate, mortality rate, and clinicopathological
      data were also compared. Increased NLR after sorafenib (HR = 3.199, 95 % CI 1.365
      7.545, P = 0.008), increased GGT after sorafenib (HR = 3.204, 95 % CI 1.333
      7.700, P = 0.009), and the presence of portal vein thrombosis (HR = 2.381, 95 %
      CI 1.064-5.328, P = 0.035) were risk factors related to RFS. By contrast,
      increased NLR after sorafenib was the only independent risk factor related to OS
      (HR = 4.647, 95 % CI 1.266-17.053, P = 0.021). Patients with increased NLR or
      increased GGT after sorafenib had a higher incidence of recurrence and death.
      Patients who had increased NLR tended to have higher preoperative levels of NLR
      and GGT. There were no differences in clinicopathological factors in patients
      with increased GGT and decreased GGT. In conclusion, increased NLR predicted a
      worse OS and RFS in patients with HCC who underwent curative resection with
      adjuvant sorafenib therapy. Increased GGT predicted a worse OS. NLR and GGT can
      be monitored dynamically before and after sorafenib therapy.

PMID- 25750041
TI  - Perspectives and practical applications of medical oncologists on defensive
      medicine (SYSIPHUS study): a study of the Palliative Care Working Committee of
      the Turkish Oncology Group (TOG).
AB  - Defensive medicine occasionally indulges unnecessary treatment requests to defend
      against lawsuits for medical errors and the use of unapproved medical
      applications. This study determines the attitudes and orientations of medical
      oncologists on defensive medicine. A cross-sectional survey was sent by e-mail to
      medical oncologists. The survey was designed to determine the participants'
      demographic characteristics and defensive medicine practices. The survey measured
      the attitudes about defensive medicine practices of the oncologists based on a
      five-point Likert scale (never, rarely, sometimes, often, and always). One
      hundred and forty-six of a total of 402 physicians serving in oncology were fully
      filled, and the rate of return invitation was 36 %. The majority of participants
      were male, with a duration of between 7 and 9 years of work as university
      hospital officials, and the mean age was 46 +/- 9 (years). International
      guidelines were followed in the most common is NCCN, and the majority of
      respondents felt that the application of these guidelines improves their
      defensive medicine. All participants of defensive medicine who stand on the basis
      of the definition were found to be more afraid of complaints by patients'
      relatives. Physicians of 45 % was noted that applying defensive medicine. Among
      the participants were the most frequent checkups of positive defensive approach
      is defined as increasing or shortening the follow-up period, while avoiding high
      risk patients were detected as described in the definition of negative defensive
      medicine. Both professional groups in both the positive and negative defensive
      medicine approach defensive medicine approach, academic tasks, work experience
      and job time, there was a significant correlation between the location. Made in
      single- and multi-variable analyses, positions were identified both positive and
      negative defensive medicine is an independent risk factor for direction.
      Improving the working conditions of young physicians to protect against medical
      error may require additional educational opportunities. 

PMID- 25750042
TI  - Induction FOLFOX followed by preoperative hyperfractionated radiotherapy plus
      bolus 5-fluorouracil in locally advanced rectal carcinoma: single arm phase I-II
      study.
AB  - Induction chemotherapy has many benefits of in locally advanced rectal cancer
      (LARC); one of these is the better control of distant failure. Hyperfractionated
      radiotherapy (HFRT) is new approach still on evaluation in preoperative setting
      of rectal cancer. We aimed to evaluate the efficacy of induction FOLFOX followed
      by HFRT in LARC. From September 2011 to December 2013, 27 patients with LARC were
      enrolled in this prospective, phase I-II study. Induction FOLFOX bolus was given
      for two cycles followed by HFRT (1.5 Gy twice day for 30 fractions over 3 weeks
      for a total of 45 Gy). 5-fluorouracil (5-FU) bolus was administrated during first
      and last 3 days of radiotherapy. Surgical resection was performed in 4-5 weeks
      further and followed by adjuvant FOLFOX bolus regimen. Twenty-one (77.8 %)
      patients were males and 22. 2 % of patients were females, and the median age at
      diagnosis was 46 years. Low sited tumor was the most presenting site (55.6 %).
      Clinically positive lymph nodes were presented in 70.4 % of patients. Twenty
      patients (74.1 %) underwent sphincter sparing procedure. Pathological complete
      response (pCR) was achieved in seven patients (25.9 %). Tumor and nodal
      downstaging were recorded in (70.3 %) and (42.1 %) of patients, respectively.
      Acute and late toxicities were in acceptable range. Two-year disease-free
      survival was 70.2 %, and overall survival was 87.5 %. Induction FOLFOX followed
      by HFRT and concurrent 5-FU improves pCR in LARC, and this combination was
      feasible with acceptable toxicity. Further evaluations are mandatory for this new
      approach.

PMID- 25750043
TI  - Infection and integration of high-risk human papillomavirus in HPV-associated
      cancer cells.
AB  - High-risk human papillomaviruses (HPV) have been associated with many human
      cancers in clinical studies. Integration of HPV into the human genome is a
      suspected etiological factor in the induction of some HPV-associated cancers. The
      characteristics of HPV integration in certain HPV-integrated cancer cells remain
      unclear. In this study, ten HPV-associated carcinoma cell lines were evaluated
      for the presence, genotype, and integration status of HPV by nested polymerase
      chain reaction. The HPV genome did not insert in the genome of a mammary cancer
      cell line (MCF7), adrenal neuroblastoma cell line (NH-6), or three esophageal
      carcinoma cell lines (KYSE150, KYSE450 and KYSE140). HPV type 18 DNA did infect
      cell lines of tongue cancer (Tca83), hepatocellular carcinoma (Hep G2), and lung
      carcinoma (A549), but the HPV type 18 genes were not transcribed into mRNA.
      However, HPV type 18 integrated into the genomes of the esophageal carcinoma cell
      lines EC9706 and EC109, and the integration sites for both cell lines were in
      loci 8q24, which is a gene desert area adjacent to fragile sites. We speculate
      that HPV transcripts are more likely to integrate near highly susceptible fragile
      sites. This study suggests that HPV integration is still a significant issue that
      needs to be fully examined and can possibly be used as individualized biomarkers
      for the early diagnosis of HPV-related cancers. 

PMID- 25750044
TI  - Mathematical modeling of the fermentation of acid-hydrolyzed pyrolytic sugars to
      ethanol by the engineered strain Escherichia coli ACCC 11177.
AB  - Pyrolysate from waste cotton was acid hydrolyzed and detoxified to yield
      pyrolytic sugars, which were fermented to ethanol by the strain Escherichia coli
      ACCC 11177. Mathematical models based on the fermentation data were also
      constructed. Pyrolysate containing an initial levoglucosan concentration of
      146.34 g/L gave a glucose yield of 150 % after hydrolysis, suggesting that other
      compounds were hydrolyzed to glucose as well. Ethyl acetate-based extraction of
      bacterial growth inhibitors with an ethyl acetate/hydrolysate ratio of 1:0.5
      enabled hydrolysate fermentation by E. coli ACCC 11177, without a standard
      absorption treatment. Batch processing in a fermenter exhibited a maximum ethanol
      yield and productivity of 0.41 g/g and 0.93 g/L.h(-1), respectively. The cell
      growth rate (r x ) was consistent with a logistic equation [Formula: see text],
      which was determined as a function of cell growth (X). Glucose consumption rate
      (r s ) and ethanol formation rate (r p ) were accurately validated by the
      equations [Formula: see text] and [Formula: see text], respectively. Together,
      our results suggest that combining mathematical models with fermenter
      fermentation processes can enable optimized ethanol production from cellulosic
      pyrolysate with E. coli. Similar approaches may facilitate the production of
      other commercially important organic substances.

PMID- 25750045
TI  - Plant-endophyte symbiosis, an ecological perspective.
AB  - Endophytism is the phenomenon of mutualistic association of a plant with a
      microorganism wherein the microbe lives within the tissues of the plant without
      causing any symptoms of disease. In addition to being a treasured biological
      resource, endophytes play diverse indispensable functions in nature for plant
      growth, development, stress tolerance, and adaptation. Our understanding of
      endophytism and its ecological aspects are overtly limited, and we have only
      recently started to appreciate its essence. Endophytes may impact plant biology
      through the production of diverse chemical entities including, but not limited
      to, plant growth hormones and by modulating the gene expression of defense and
      other secondary metabolic pathways of the host. Studies have shown differential
      recruitment of endophytes in endophytic populations of plants growing in the same
      locations, indicating host specificity and that endophytes evolve in a
      coordinated fashion with the host plants. Endophytic technology can be employed
      for the efficient production of agricultural and economically important plants
      and plant products. The rational application of endophytes to manipulate the
      microbiota, intimately associated with plants, can help in enhancement of
      production of agricultural produce, increased production of key metabolites in
      medicinal and aromatic plants, as well as adaption to new bio-geographic regions
      through tolerance to various biotic and abiotic conditions. However, the
      potential of endophytic biology can be judiciously harnessed only when we obtain
      insight into the molecular mechanism of this unique mutualistic relationship. In
      this paper, we present a discussion on endophytes, endophytism, their
      significance, and diverse functions in nature as unraveled by the latest research
      to understand this universal natural phenomenon.

PMID- 25750047
TI  - The glyoxylate shunt is essential for CO2-requiring oligotrophic growth of
      Rhodococcus erythropolis N9T-4.
AB  - Rhodococcus erythropolis N9T-4 shows extremely oligotrophic growth requiring
      atmospheric CO2 and forms its colonies on an inorganic basal medium (BM) without
      any additional carbon source. Screening of a random mutation library constructed
      by a unique genome deletion method that we established indicated that the aceA,
      aceB, and pckG genes encoding isocitrate lyase, malate synthase, and
      phosphoenolpyruvate carboxykinase, respectively, were requisite for survival on
      BM plates. The aceA- and aceB deletion mutants and the pckG deletion mutant grew
      well on BM plates containing L-malate and D-glucose, respectively, suggesting
      that the glyoxylate (GO) shunt and gluconeogenesis are essential for the
      oligotrophic growth of N9T-4. Interestingly, most of the enzyme activities in the
      TCA cycle were observed in the cell-free extract of N9T-4, with perhaps the most
      important exception being alpha-ketoglutarate dehydrogenase (KGDH) activity.
      Instead of the KGDH activity, we detected a remarkable level of alpha
      ketoglutarate decarboxylase (KGD) activity, which is the activity exhibited by
      the E1 component of the KGDH complex in Mycobacterium tuberculosis. The
      recombinant KGD of N9T-4 catalyzed the decarboxylation of alpha-ketoglutarate to
      form succinic semialdehyde (SSA) in a time-dependent manner. Since N9T-4 also
      showed a detectable SSA dehydrogenase activity, we concluded that N9T-4 possesses
      a variant TCA cycle, which uses SSA rather than succinyl-CoA. These results
      suggest that oligotrophic N9T-4 cells utilize the GO shunt to avoid the loss of
      carbons as CO2 and to conserve CoA units in the TCA cycle. 

PMID- 25750046
TI  - Lactic acid bacteria--20 years exploring their potential as live vectors for
      mucosal vaccination.
AB  - Lactic acid bacteria (LAB) are a diverse group of Gram-positive, nonsporulating,
      low G + C content bacteria. Many of them have been given generally regarded as
      safe status. Over the past two decades, intensive genetic and molecular research
      carried out on LAB, mainly Lactococcus lactis and some species of the
      Lactobacillus genus, has revealed new, potential biomedical LAB applications,
      including the use of LAB as adjuvants, immunostimulators, or therapeutic drug
      delivery systems, or as factories to produce therapeutic molecules. LAB enable
      immunization via the mucosal route, which increases effectiveness against
      pathogens that use the mucosa as the major route of entry into the human body. In
      this review, we concentrate on the encouraging application of Lactococcus and
      Lactobacillus genera for the development of live mucosal vaccines. First, we
      present the progress that has recently been made in the field of developing tools
      for LAB genetic manipulations, which has resulted in the successful expression of
      many bacterial, parasitic, and viral antigens in LAB strains. Next, we discuss
      the factors influencing the efficacy of the constructed vaccine prototypes that
      have been tested in various animal models. Apart from the research focused on an
      application of live LABs as carriers of foreign antigens, a lot of work has been
      recently done on the potential usage of nonliving, nonrecombinant L. lactis
      designated as Gram-positive enhancer matrix (GEM), as a delivery system for
      mucosal vaccination. The advantages and disadvantages of both strategies are also
      presented.

PMID- 25750048
TI  - Biochemical and functional characterizations of tyrosine phosphatases from
      pathogenic and nonpathogenic mycobacteria: indication of phenyl cyclopropyl
      methyl-/phenyl butenyl azoles as tyrosine phosphatase inhibitors.
AB  - Tyrosine phosphorylation is one of the most common means of posttranslational
      modifications which can generate novel recognition motifs for protein
      interactions and thereafter affecting cellular localization, protein stability,
      and enzyme activity. Mycobacterium tuberculosis (Mtb) possesses a wide range of
      signal transduction systems, including two protein tyrosine phosphatases (PtpA
      and PtpB). Since functional diversities between protein tyrosine phosphatases
      (PTPases) are illustrated by regulatory domains and subunits, we have
      characterized the nature of tyrosine phosphatases from slow-grower pathogenic
      species Mtb and from fast-grower nonpathogenic species Mycobacterium smegmatis
      (MS). The findings delineate that the enzymes present in MS have significantly
      lesser phosphatase activity than PTPases of Mtb as evidenced by low K cat/K m of
      recombinantly expressed proteins. The K cat/K m for Mtb PtpA was 500-1000-fold
      higher than MS PTPases. We have designed and synthesized phenyl cyclopropyl
      methyl-/phenyl butenyl azoles which inhibit growth of mycobacteria, in culture
      and in macrophages. The mechanism of efficacy of these compounds against
      mycobacteria was identified and suggested that the inhibition may possibly be
      mediated via the targeting of Mtb tyrosine phosphatase. The results further added
      that these compounds exclusively inhibit PtpA of Mtb. 

PMID- 25750049
TI  - Biosynthesis and production of glycosylated flavonoids in Escherichia coli:
      current state and perspectives.
AB  - Flavonoids are plant secondary metabolites containing several hydroxyl groups
      that are targets for modification reactions such as methylation and
      glycosylation. In plants, flavonoids are present as glycones. Although glucose is
      the most common sugar attached to flavonoids, arabinose, galactose, glucuronic
      acid, rhamnose, and xylose are also linked to flavonoids. Depending on the kind
      and the position of the attached sugar, flavonoid glycones show different
      biological properties. Flavonoid-O-glycosides are synthesized by uridine
      diphosphate-dependent glycosyltransferases (UGTs), which use nucleotide sugar as
      a sugar donor and a diverse compound as a sugar acceptor. Recently, diverse
      flavonoid-O-glycosides have been synthesized in Escherichia coli by introducing
      UGTs from plants and bacteria and modifying endogenous pathways. The nucleotide
      sugar biosynthesis pathway in E. coli has been engineered to provide the proper
      nucleotide sugar for flavonoid-O-glycoside biosynthesis. In this review, we will
      discuss recent advances in flavonoid-O-glycoside biosynthesis using engineered E.
      coli.

PMID- 25750050
TI  - Modeling the transfer of arsenic from soil to carrot (Daucus carota L.)--a
      greenhouse and field-based study.
AB  - Reliable empirical models describing arsenic (As) transfer in soil-plant systems
      are needed to estimate the human As burden from dietary intake. A greenhouse
      experiment was conducted in parallel with a field trial located at three sites
      through China to develop and validate soil-plant transfer models to predict As
      concentrations in carrot (Daucus carota L.). Stepwise multiple linear regression
      relationships were based on soil properties and the pseudo total (aqua regia) or
      available (0.5 M NaHCO3) soil As fractions. Carrot As contents were best
      predicted by the pseudo total soil As concentrations in combination with soil pH
      and Fe oxide, with the percentage of variation explained being up to 70 %. The
      constructed prediction model was further validated and improved to avoid
      overprotection using data from the field trial. The final obtained model is of
      great practical relevance to the prediction of As uptake under field conditions.

PMID- 25750051
TI  - Consideration of the bioavailability of metal/metalloid species in freshwaters:
      experiences regarding the implementation of biotic ligand model-based approaches
      in risk assessment frameworks.
AB  - After the scientific development of biotic ligand models (BLMs) in recent
      decades, these models are now considered suitable for implementation in
      regulatory risk assessment of metals in freshwater bodies. The BLM approach has
      been described in many peer-reviewed publications, and the original complex BLMs
      have been applied in prospective risk assessment reports for metals and metal
      compounds. BLMs are now also recommended as suitable concepts for the site
      specific evaluation of monitoring data in the context of the European Water
      Framework Directive. However, the use is hampered by the data requirements for
      the original BLMs (about 10 water parameters). Recently, several user-friendly
      BLM-based bioavailability software tools for assessing the aquatic toxicity of
      relevant metals (mainly copper, nickel, and zinc) became available. These tools
      only need a basic set of commonly determined water parameters as input (i.e., pH,
      hardness, dissolved organic matter, and dissolved metal concentration). Such
      tools seem appropriate to foster the implementation of routine site-specific
      water quality assessments. This work aims to review the existing bioavailability
      based regulatory approaches and the application of available BLM-based
      bioavailability tools for this purpose. Advantages and possible drawbacks of
      these tools (e.g., feasibility, boundaries of validity) are discussed, and
      recommendations for further implementation are given. 

PMID- 25750052
TI  - Hypersexual, Sexually Compulsive, or Just Highly Sexually Active? Investigating
      Three Distinct Groups of Gay and Bisexual Men and Their Profiles of HIV-Related
      Sexual Risk.
AB  - Emerging research supports the notion that sexual compulsivity (SC) and
      hypersexual disorder (HD) among gay and bisexual men (GBM) might be
      conceptualized as comprising three groups-Neither SC nor HD; SC only, and Both SC
      and HD-that capture distinct levels of severity across the SC/HD continuum. We
      examined data from 370 highly sexually active GBM to assess how the three groups
      compare across a range of risk factors for HIV infection. Comparisons focused on
      psychosexual measures-temptation for condomless anal sex (CAS), self-efficacy for
      avoiding CAS, sexual excitation and inhibition-as well as reports of actual
      sexual behavior. Nearly half (48.9 %) of this highly sexually active sample was
      classified as Neither SC nor HD, 30 % as SC Only, and 21.1 % as Both SC and HD.
      While we found no significant differences between the three groups on reported
      number of male partners, anal sex acts, or anal sex acts with serodiscordant
      partners, the Both SC and HD group reported higher numbers of CAS acts and CAS
      acts with serodiscordant partners and also had a higher proportion of their anal
      sex acts without condoms compared to the SC Only group. Our findings support the
      validity of a three-group classification system of SC/HD severity in
      differentiating psychosexual and HIV-related sexual risk behavior outcomes in a
      sample of GBM who report similarly high levels of sexual activity.
      Notwithstanding the need for sex positive HIV prevention programs, interventions
      that attempt to help Both SC and HD men deal with distress and address their
      psychosexual needs specifically may derive HIV prevention benefits. 

PMID- 25750053
TI  - A study on toxic and essential elements in rice from the Republic of Kazakhstan:
      comparing the level of contamination in rice from the European Community.
AB  - Selected toxic elements (total As, Cd, Cr, Hg, Pb, Sr, U and V) and essential
      elements (Co, Cu, Fe, Mn and Zn) were analyzed using an inductively coupled
      plasma mass spectrometry (ICP-MS) in unpolished and milled rice collected from
      Kazakhstan and milled rice from Spain and Portugal to evaluate the potential
      health risk to the population. Arsenic species (arsenite, arsenate,
      arsenobetaine, dimethylarsinate and monomethilarsonate) were analyzed using HPLC
      IC-MS. From 146 samples analyzed, none of them exceeded the maximum limit set by
      the European Legislation for Cd or Pb or values recommended by the Codex
      Alimentarius. Concentrations of Sr, U and V were below LOD and those of Hg, Pb,
      Co and Cr between <LOD and 0.54 mg/kg (highest concentration of Cr) in milled
      rice. Portuguese rice samples contained the highest mean concentration of As, Hg,
      Pb, Co, Cr, Cu, Mn and Zn. The highest mean of arsenobetaine (0.001 mg/kg),
      dimethylarsinate (0.27 mg/kg) and monomethilarsonate (0.02 mg/kg) was found in
      Spanish rice and that of arsenite (0.30 mg/kg) in Kazakh rice. Inorganic As in
      samples from Kazakhstan was above the ML (0.2 mg/kg) proposed by FAO/WHO, but in
      seven samples from Spain and in four from Portugal were above the limit. The
      estimated weekly intake of total or inorganic As(III, V), Cd, Hg and Pb for rice
      consumption by Kazakh, Spanish and Portuguese adults and children was lower than
      the provisional tolerable weekly intake established by Joint FAO/WHO Expert
      Committee on Food Additives and the European Food Safety Authority. 

PMID- 25750054
TI  - Heavy metals and parasitic geohelminths toxicity among geophagous pregnant women:
      a case study of Nakuru Municipality, Kenya.
AB  - Geophagia is defined as deliberate consumption of earths' materials, e.g. soil,
      clay and soft stones. The practice is widespread among pregnant women, and there
      are conflicting views as to whether it is beneficial to health or not. Geophagic
      materials may be a source of micronutrients though the materials may bind the
      micronutrients thus reducing or hindering their bioavailability in the body.
      Geophagia is closely associated with geohelminthic infections among pregnant
      women and heavy metal poisoning, which constitute significant public health
      problem in many developing countries such as Kenya. In our research, the
      geophagic materials consumed by the pregnant women were studied. A total of 38
      geophagic materials in the possession by different pregnant women were analysed.
      The collected samples were subjected to standard digestion procedures and
      analysed for zinc, lead and iron by atomic absorption spectroscopy. Results
      indicated that the geophagic materials contained elevated levels of Fe at mean
      concentration value of 80.10 ppm, Pb at 3.28 ppm and Zn 1.81 ppm for a 1.00 g
      sample. An average of 20 g of the geophagic materials was being consumed per day.
      Based on the average consumption, the pregnant women were exposed to 65.52 ppm Pb
      per day, 36.2 ppm Zn per day and 1602 ppm Fe per day. Lead exceeded the WHO-lead
      exposure limits of 25 ppm/day for pregnant women. The materials were also
      subjected to microscopic examination for Ascaris lumbricoides, Trichuris
      trichiura, Taenia Spp., Necator americanus and Ancylostoma duodenale. In
      conclusion, the women were exposed to heavy metals-iron, zinc and lead, but there
      was no observable eggs, larvae or adult species of the geohelminths. The key
      recommendation was that there is need to integrate public health education on
      geophagia, lead screening and testing with antenatal support care systems. This
      will enhance maternal and child health, thus reducing infant and maternal
      morbidity and mortality rates. 

PMID- 25750055
TI  - Melt processing and property testing of a model system of plastics contained in
      waste from electrical and electronic equipment.
AB  - In the present research, blending of polymers used in electrical and electronic
      equipment, i.e. acrylonitrile-butadiene-styrene terpolymer, polycarbonate and
      polypropylene, was performed in a twin-screw extruder, in order to explore the
      effect process parameters on the mixture properties, in an attempt to determine
      some characteristics of a fast and economical procedure for waste management. The
      addition of polycarbonate in acrylonitrile-butadiene-styrene terpolymer seemed to
      increase its thermal stability. Also, the addition of polypropylene in
      acrylonitrile-butadiene-styrene terpolymer facilitates its melt processing,
      whereas the addition of acrylonitrile-butadiene-styrene terpolymer in
      polypropylene improves its mechanical performance. Moreover, the upgrading of the
      above blends by incorporating 2 phr organically modified montmorillonite was
      investigated. The prepared nanocomposites exhibit greater tensile strength,
      elastic modulus and storage modulus, as well as higher melt viscosity, compared
      with the unreinforced blends. The incorporation of montmorillonite nanoplatelets
      in polycarbonate-rich acrylonitrile-butadiene-styrene terpolymer/polycarbonate
      blends turns the thermal degradation mechanism into a two-stage process.
      Alternatively to mechanical recycling, the energy recovery from the combustion of
      acrylonitrile-butadiene-styrene terpolymer/polycarbonate and acrylonitrile
      butadiene-styrene terpolymer/polypropylene blends was recorded by measuring the
      gross calorific value. Comparing the investigated polymers, polypropylene
      presents the higher gross calorific value, followed by acrylonitrile-butadiene
      styrene terpolymer and then polycarbonate. The above study allows a rough
      comparative evaluation of various methodologies for treating plastics from waste
      from electrical and electronic equipment.

PMID- 25750056
TI  - Reduction of acid rock drainage using steel slag in cover systems over sulfide
      rock waste piles.
AB  - The extraction of gold, coal, nickel, uranium, copper and other earth-moving
      activities almost always leads to environmental damage. In metal and coal
      extraction, exposure of sulfide minerals to the atmosphere leads to generation of
      acid rock drainage (ARD) and in underground mining to acid mine drainage (AMD)
      due to contamination of infiltrating groundwater. This study proposes to develop
      a reactive cover system that inhibits infiltration of oxygen and also releases
      alkalinity to increase the pH of generated ARD and attenuate metal contaminants
      at the same time. The reactive cover system is constructed using steel slag, a
      waste product generated from steel industries. This study shows that this type of
      cover system has the potential to reduce some of the adverse effects of sulfide
      mine waste disposal on land. Geochemical and geotechnical characterization tests
      were carried out. Different proportions of sulfide mine waste and steel slag were
      studied in leachate extraction tests. The best proportion was 33% of steel slag
      in dry weight. Other tests were conducted as follows: soil consolidation,
      saturated permeability and soil water characteristic curve. The cover system was
      numerically modeled through unsaturated flux analysis using Vadose/w. The
      solution proposed is an oxygen transport barrier that allows rain water
      percolation to treat the ARD in the waste rock pile. The results showed that the
      waste pile slope is an important factor and the cover system must have 5 m
      thickness to achieve an acceptable effectiveness. 

PMID- 25750057
TI  - Robotic liver surgery: preliminary experience in a tertiary hepato-biliary unit.
AB  - Minimally invasive liver surgery is performed with increasing frequency by
      hepatic surgeons. Laparoscopy was the first approach to be used and it is
      currently safely feasible in selected patients by experienced surgeons. Minor and
      major laparoscopic hepatectomies are now performed as a routine procedure in
      tertiary referral centers, with increasing evidence of long-term results
      comparable to traditional surgery together with the advantages of a minimally
      invasive approach. Robotic surgery, first developed for military purposes, showed
      to overcome some of the limits of laparoscopy, with an improved visual
      magnification, a 3-dimensional view and enhanced dexterity with better movement
      control. This allows an easier approach for resections in the posterior segments
      and for lesions close to major vessels. We present our preliminary experience of
      20 consecutive robotic liver resection. Indications were colo-rectal liver
      metastasis (n = 7), hepatocellular carcinoma (n = 6), liver hemangioma (n = 2),
      biliary cystoadenoma (n = 2), breast cancer liver metastasis (n = 1), lung cancer
      liver metastasis (n = 1), symptomatic left liver lithiasis (n = 1). No conversion
      to laparotomy have been made and no hepatic pedicle clamping has been performed.
      The median duration of surgery was 141 min. There was no mortality, global
      morbidity was 10%. Median tumor size was 36 mm. Median post-operative length of
      stay was 5.7 days. Robotic surgery can be safely performed by experienced hepatic
      surgeons, resections of lesions in the posterior segments and close to the major
      vessels seem to be the best indication. Further studies are needed to clarify the
      exact role of robotics in liver surgery.

PMID- 25750058
TI  - Association of magnesium in serum and urine with carotid intima-media thickness
      and serum lipids in middle-aged and elderly Chinese: a community-based cross
      sectional study.
AB  - OBJECTIVE: Previous studies suggested that magnesium (Mg) might protect against
      atherosclerosis, but data were scarce in an Asian population. We examined the
      association of Mg levels in serum and urine with carotid intima-media thickness
      (cIMT) and serum lipids in Chinese adults. METHODS: This community-based cross
      sectional study recruited 2,837 participants aged 40-75 years in Guangzhou,
      China. General information, lifestyle factors, serum and urinary concentrations
      of Mg and cardiometabolic factors were determined. The cIMTs of the common
      carotid artery (CCA) and the carotid bifurcation (BIF) were measured
      ultrasonographically. RESULTS: The mean (SD) concentration of serum Mg was 0.85
      (0.07) mmol/L and median (IQR) for urinary Mg excretion was 2.29 (1.56-3.51)
      mmol/L. After adjustment for potential covariates, both serum and the urinary
      concentrations of Mg were inversely associated with CCA-IMT, but not with BIF
      IMT. The regression coefficients (standard errors) were -100 (29) um (total), -86
      (34) um (women) and -117 (52) um (men) CCA-IMT per 1 mmol/L of serum Mg, and -41
      (8) um (total), -41 (10) um (women) and -44 (15) um (men) CCA-IMT per 1 unit of
      urinary Mg/creatinine (log mmol/mmol) (all p < 0.05), respectively. Higher serum
      Mg levels were associated with higher total cholesterol, HDLc, LDLc and
      triglyceride, but lower non-HDLc/HDLc in total population (all p < 0.05). Similar
      relationships of urinary Mg with lipoproteins were also found in total population
      (all p < 0.05). CONCLUSION: Higher levels of serum and urinary Mg are associated
      with lower CCA-IMTs, and the role of Mg in lipid metabolism needs further
      investigation.

PMID- 25750059
TI  - Iodine status in healthy pregnant women in Korea: a first report.
AB  - PURPOSE: Proper iodine intake is important during pregnancy for both fetal
      neurodevelopment and maternal thyroid function. Korea is known as a high iodine
      intake area. However, there are no data regarding iodine status in pregnant
      Korean women. Therefore, we evaluated the iodine status of pregnant women in
      Korea by measuring urine iodine concentration. METHODS: This study had an
      observational, prospective design. We enrolled 344 healthy pregnant women who
      visited Samsung Medical Center in Korea for a routine antenatal checkup between
      April 2012 and September 2013. We measured iodine and creatinine concentration
      (Cr) in spot urine samples and TSH level in serum at the time of enrollment.
      RESULTS: The median urinary iodine concentration (UIC) and UIC adjusted by Cr
      were 427.3 MUg/L and 447.9 MUg/gCr, respectively. There was no difference in
      median UIC according to trimester of pregnancy (P value = 0.953). Serum TSH level
      was not different according to UIC level when subjects were grouped according to
      WHO iodine recommendations (P value = 0.401). CONCLUSIONS: The median UIC of
      healthy pregnant women in Korea was 427.3 MUg/L and 447.9 MUg/gCr, which are more
      than adequate according to WHO criteria. Considering the wide range of UIC, we
      recommend active education about adequate iodine intake during pregnancy in areas
      where iodine intake is more than adequate according to WHO criteria.

PMID- 25750060
TI  - The complexity of dialytic therapy in hyperammonemic neonates.
AB  - The utilization of renal replacement therapy (RRT) in the setting of hyperammonia
      is a rare and complicated occurrence. Data demonstrate that the quicker the
      ammonia level is normalized, the better the neurological outcome. The optimal
      form of RRT is often decided by local practice. The recent work by Picca and
      colleagues details a larger series of children who underwent RRT for hyperammonia
      and adds some credence to the use of peritoneal dialysis (PD) in this population.
      While these authors conclude that PD is not optimal, they do note that the use of
      PD may be an option when other forms of RRT are not available. The results
      reinforce the general maxim that you should continue to do that which you do well
      and often, which in this context refers to continuing to use your form of RRT
      until alternative modalities are available. 

PMID- 25750062
TI  - Disruption of the proximal tibiofibular joint in the setting of multi-ligament
      knee injury.
AB  - Instability of the proximal tibiofibular joint is a relatively uncommon condition
      when in isolation; however, instability of the proximal tibiofibular joint is far
      more frequent in those presenting with a severe multi-ligament injury of the
      knee. If this joint is left unstable, repair of a co-existent injury of the
      posterolateral corner may fail, regardless of the proficiency of the technique.
      We present two patients with disruption of the proximal tibiofibular joint,
      including the MRI appearance, who initially presented to our hospital for
      management of significant polytrauma, as well as multi-ligament injury of the
      ipsilateral knee. 

PMID- 25750061
TI  - Clinically Combating Reward Deficiency Syndrome (RDS) with Dopamine Agonist
      Therapy as a Paradigm Shift: Dopamine for Dinner?
AB  - Everyday, there are several millions of people that are increasingly unable to
      combat their frustrating and even fatal romance with getting high and/or
      experiencing "normal" feelings of well-being. In the USA, the FDA has approved
      pharmaceuticals for drug and alcohol abuse: tobacco and nicotine replacement
      therapy. The National Institute on Drug Abuse (NIDA) and the National Institute
      on Alcohol Abuse and Alcoholism (NIAAA) remarkably continue to provide an
      increasing understanding of the intricate functions of brain reward circuitry
      through sophisticated neuroimaging and molecular genetic applied technology.
      Similar work is intensely investigated on a worldwide basis with enhanced clarity
      and increased interaction between not only individual scientists but across many
      disciplines. However, while it is universally agreed that dopamine is a major
      neurotransmitter in terms of reward dependence, there remains controversy
      regarding how to modulate its role clinically to treat and prevent relapse for
      both substance and non-substance-related addictive behaviors. While the existing
      FDA-approved medications promote blocking dopamine, we argue that a more prudent
      paradigm shift should be biphasic-short-term blockade and long-term upregulation,
      enhancing functional connectivity of brain reward circuits. 

PMID- 25750064
TI  - Lysobacter lycopersici sp. nov., isolated from tomato plant Solanum lycopersicum.
AB  - A Gram-stain negative, aerobic, rod-shaped and non-spore-forming bacterium, CC-Bw
      6(T) was isolated from chopped tomato stems. Analysis of the 16S rRNA gene
      sequence of the strain CC-Bw-6(T) showed its affiliation with the genus
      Lysobacter within the class Gammaproteobacteria. Strain CC-Bw-6(T) was found to
      be most closely related to Lysobacter panaciterrae KCTC 12601(T) (97.0%) and
      Lysobacter daecheongensis KCTC 12600(T) (96.8%), and showed lower similarity
      (<96.5%) to other Lysobacter species. DNA-DNA relatedness between strain CC-Bw
      6(T) and L. panaciterrae KCTC 12601(T) was 10.8%, the G+C content of the genomic
      DNA is 69.9 mol%. Strain CC-Bw-6(T) was determined to possess C(11:0) iso,
      C(11:0) iso 3OH, C(14:0) iso, C(15:0) anteiso, C(15:1) omega5c, C(16:1) omega5c,
      C(16:0), C(15:0) iso, C(16:0) iso, C(17:0) iso and C(16:0) 10-methyl/C(17:1) iso
      omega9c as predominant fatty acids. The major polar lipid profile consists of
      phosphatidylethanolamine, phosphatidylglycerol, diphosphatidylglycerol and
      unidentified phospholipids. The predominant polyamine is spermidine, and
      ubiquinone-8 is the predominant respiratory quinone. Analysis of phenotypic, geno
      and phylogenetic characteristics revealed a distinct taxonomic position of
      strain CC-Bw-6(T) with respect to other Lysobacter species. Based on the
      phylogenetic, chemotaxonomic and phenotypic data presented here, we propose a
      novel species with the name Lysobacter lycopersici sp. nov. The type strain is CC
      Bw-6(T) (=BCRC 80612(T) = JCM 19164(T)).

PMID- 25750063
TI  - Mediterranean diet and leukocyte telomere length in a multi-ethnic elderly
      population.
AB  - Leukocyte telomere length (LTL) is considered as the marker of biological aging
      and may be related to environmental factors. The current study aimed to examine
      the relation between Mediterranean-type diet and LTL. We used a cross-sectional
      study of 1743 multi-ethnic community residents of New York aged 65 years or
      older. Mediterranean-type diet (MeDi) was calculated from dietary information
      collected using a food frequency questionnaire. LTL was measured from leukocyte
      DNA using a real-time PCR method to measure T/S ratio, the ratio of telomere (T)
      to single-copy gene (S) sequence. Regression analysis showed that the MeDi score
      was not associated with LTL in the overall study population (beta = 12.5; p =
      0.32) after adjusting for age, sex, education, ethnicity, caloric intake,
      smoking, and physical and leisure activities. However, we found a significant
      association between MeDi and LTL among non-Hispanic whites (beta = 48.3; p =
      0.05), and the results held after excluding dementia subjects (beta = 49.6; p =
      0.05). We further found that, in the whole population, vegetable and cereal
      consumption above the sex-specific population median was associated with longer
      LTL (beta = 89.1, p = 0.04) and shorter LTL (beta = -93.5; p = 0.03),
      respectively. Among non-Hispanic whites, intake of meat or dairy below sex
      specific population medians was associated with longer LTL (beta = 154.7, p =
      0.05; beta = 240.5, p < 0.001, respectively). We found that higher adherence to a
      MeDi was associated with longer LTL among whites but not among African Americans
      and Hispanics. Additionally, a diet high in vegetables but low in cereal, meat,
      and dairy might be associated with longer LTL among healthy elderly.

PMID- 25750065
TI  - Effects of saltwater intrusion on pinewood vegetation using satellite ASTER data:
      the case study of Ravenna (Italy).
AB  - The San Vitale pinewood (Ravenna, Italy) is part of the remaining wooded areas
      within the southeastern Po Valley. Several studies demonstrated a widespread
      saltwater intrusion in the phreatic aquifer caused by natural and human factors
      in this area as the whole complex coastal system. Groundwater salinization
      affects soils and vegetation, which takes up water from the shallow aquifer.
      Changes in groundwater salinity induce variations of the leaf properties and
      vegetation cover, recognizable by satellite sensors as a response to different
      spectral bands. A procedure to identify stressed areas from satellite remote
      sensing data, reducing the expensive and time-consuming ground monitoring
      campaign, was developed. Multispectral Advanced Spaceborne Thermal Emission and
      Reflection Radiometer (ASTER) data, acquired between May 2005 and August 2005,
      were used to calculate Normalized Difference Vegetation Index (NDVI). Within the
      same vegetation type (thermophilic deciduous forest), the areas with the higher
      vegetation index were taken as reference to identify the most stressed areas
      using a statistical approach. To confirm the findings, a comparison was conducted
      using contemporary groundwater salinity data. The results were coherent in the
      areas with highest and lowest average NDVI values. Instead, to better understand
      the behavior of the intermediate areas, other parameters influencing vegetation
      (meteorological data, water table depth, and tree density) were added for the
      interpretation of the results. 

PMID- 25750066
TI  - Spatio-temporal evaluation of Yamchi Dam basin water quality using Canadian water
      quality index.
AB  - In recent years, the growth of population and increase of the industries around
      the tributaries of Yamchi Dam basin have led to deterioration of dam water
      quality. This study aimed to evaluate the quality of the Yamchi Dam basin water,
      which is used for drinking and irrigation consumptions using Canadian Water
      Quality Index (CWQI) model, and to determine the main water pollution sources of
      this basin. Initially, nine sampling stations were selected in the sensitive
      locations of the mentioned basin's tributaries, and 12 physico-chemical
      parameters and 2 biological parameters were measured. The CWQI for drinking
      consumptions was under 40 at all the stations indicating a poor water quality for
      drinking consumptions. On the other hand, the CWQI was 62-100 for irrigation at
      different stations; thus, the water had an excellent to fair quality for
      irrigation consumptions. Almost in all the stations, the quality of irrigation
      and drinking water in cold season was better. Besides, for drinking use, total
      coliform and fecal coliform had the highest frequency of failure, and total
      coliform had the maximum deviation from the specified objective. For irrigation
      use, total suspended solids had the highest frequency of failure and deviation
      from the objective in most of the stations. The pisciculture center, aquaculture
      center, and the Nir City wastewater discharge were determined as the main
      pollution sources of the Yamchi Dam basin. Therefore, to improve the water
      quality in this important surface water resource, urban and industrial wastewater
      treatment prior to disposal and more stringent environmental legislations are
      recommended. 

PMID- 25750067
TI  - Assessment of ground and surface water quality along the river Varuna, Varanasi,
      India.
AB  - Multivariate statistical techniques were employed for monitoring of ground
      surface water interactions in rivers. The river Varuna is situated in the Indo
      Gangetic plain and is a small tributary of river Ganga. The study area was
      monitored at seven sampling sites for 3 years (2010-12), and eight physio
      chemical parameters were taken into account for this study. The data obtained
      were analysed by multivariate statistical techniques so as to reveal the
      underlying implicit information regarding proposed interactions for the relevant
      area. The principal component analysis (PCA) and cluster analysis (CA), and the
      results of correlations were also studied for all parameters monitored at every
      site. Methods used in this study are essentially multivariate statistical in
      nature and facilitate the interpretation of data so as to extract meaningful
      information from the datasets. The PCA technique was able to compress the data
      from eight to three parameters and captured about 78.5% of the total variance by
      performing varimax rotation over the principal components. The varifactors, as
      yielded from PCA, were treated by CA which grouped them convincingly into three
      groups having similar characteristics and source of contamination. Moreover, the
      loading of variables on significant PCs showed correlations between various
      ground water and surface water (GW-SW) parameters. The correlation coefficients
      calculated for various physiochemical parameters for ground and surface water
      established the correlations between them. Thus, this study presents the utility
      of multivariate statistical techniques for evaluation of the proposed
      interactions and effective future monitoring of potential sites.

PMID- 25750068
TI  - Seasonal and intradiurnal variation of airborne pollen concentrations in Bodrum,
      SW Turkey.
AB  - An aeropalynological study was performed in Bodrum, the famous tourism center in
      southwestern Turkey with a Hirst-type volumetric 7-day pollen and spore trap for
      2 years (2007-2008). In Bodrum, 25,099 pollen grains as a mean value belonging to
      41 taxa were recorded annually during the study period, and pollen grains from
      woody plant taxa had the largest atmospheric contribution of 86.99% and 24 taxa.
      However, 17 herbaceous plant taxa constituted 12.82% of the annual total pollen
      count, and 0.19% were unidentified. An average annual pollen index of 22.66% was
      recorded in March, despite differences from year to year. The highest pollen
      variability of 34 taxa was recorded in April and May. Predominant pollen types
      belonged to Cupressaceae/Taxaceae (42.73%), Quercus (15.95%), Pinus (9.78%), Olea
      europaea (9.04%), Poaceae (5.50%), Betula (1.82%), Pistacia (1.74%), Morus
      (1.72%), Urticaceae (1.46%), and Plantago (1.28%) and generated 91.03 of the
      annual total. In total, 32.59% of the mean annual total pollen index was recorded
      in the morning, and less pollen was recorded in the evening (18.71%). Maximum
      pollen concentration was recorded between 11:00 and 12:00 a.m.

PMID- 25750069
TI  - The determination of physiological and DNA changes in seedlings of maize (Zea
      mays L.) seeds exposed to the waters of the Gediz River and copper heavy metal
      stress.
AB  - In this study, the effects of the heavy metal-polluted waters of the Gediz River,
      which flow into the Aegean Sea, and different concentrations of copper (Cu)
      solutions on maize (Zea mays L.) seedlings are investigated with physiological
      parameters and random amplified polymorphic DNA (RAPD) assay. Results displayed
      physiologically a significant difference in root and stem length between the
      control seedlings and the seedlings grown with the waters of the Gediz River.
      Also, the certain ascending concentrations of copper solution (80, 160, 320, 640,
      and 1280 ppm) caused a significant decrease in root and stem length of seedlings
      compared to the control seedlings. As a result of the waters of the Gediz River
      and copper solution treatment, the changes occurred in RAPD profiles of seedlings
      observed as variations like increment and/or loss of bands compared with the
      control seedlings. And these changes were reflected as a decrease in genomic
      template stability (GTS, changes in RAPD profile) derived by genotoxicity. RAPD
      band profiles and GTS values showed consistent results with physiological
      parameter. In conclusion, the study revealed the environmental risk and negative
      effect of waters of the Gediz River on maize seedlings and the suitability of
      RAPD assay for the detection of environmental toxicology. 

PMID- 25750070
TI  - HIV eradication symposium: will the brain be left behind?
AB  - On 18 July 2014, the National Institute of Mental Health in collaboration with
      ViiV Health Care and Boehringer Ingelheim supported a symposium on HIV
      eradication and what it meant for the brain. The symposium was an affiliated
      event to the 20th International AIDS Conference. The meeting was held in
      Melbourne, Australia, and brought together investigators currently working on HIV
      eradication together with investigators who are working on the neurological
      complications of HIV. The purpose of the meeting was to bring the two fields of
      HIV eradication and HIV neurology together to foster dialogue and cross talk to
      move the eradication field forward in the context of issues relating to the brain
      as a potential reservoir of HIV. The outcomes of the symposium were that there
      was substantive but not definitive evidence for the brain as an HIV reservoir
      that will provide a challenge to HIV eradication. Secondly, the brain as a
      clinically significant reservoir for HIV is not necessarily present in all
      patients. Consequently, there is an urgent need for the development of biomarkers
      to identify and quantify the HIV reservoir in the brain. Lastly, when designing
      and developing eradication strategies, it is critical that approaches to target
      the brain reservoir be included. 

PMID- 25750071
TI  - Genetic diversity and proviral DNA load in different neural compartments of HIV-1
      subtype C infection.
AB  - In India, the low prevalence of HIV-associated dementia (HAD) in the Human
      immunodeficiency virus type 1 (HIV-1) subtype C infection is quite paradoxical
      given the high-rate of macrophage infiltration into the brain. Whether the direct
      viral burden in individual brain compartments could be associated with the
      variability of the neurologic manifestations is controversial. To understand this
      paradox, we examined the proviral DNA load in nine different brain regions and
      three different peripheral tissues derived from ten human subjects at autopsy.
      Using a highly sensitive TaqMan probe-based real-time PCR, we determined the
      proviral load in multiple samples processed in parallel from each site. Unlike
      previously published reports, the present analysis identified uniform proviral
      distribution among the brain compartments examined without preferential
      accumulation of the DNA in any one of them. The overall viral DNA burden in the
      brain tissues was very low, approximately 1 viral integration per 1000 cells or
      less. In a subset of the tissue samples tested, the HIV DNA mostly existed in a
      free unintegrated form. The V3-V5 envelope sequences, demonstrated a brain
      specific compartmentalization in four of the ten subjects and a phylogenetic
      overlap between the neural and non-neural compartments in three other subjects.
      The envelope sequences phylogenetically belonged to subtype C and the majority of
      them were R5 tropic. To the best of our knowledge, the present study represents
      the first analysis of the proviral burden in subtype C postmortem human brain
      tissues. Future studies should determine the presence of the viral antigens, the
      viral transcripts, and the proviral DNA, in parallel, in different brain
      compartments to shed more light on the significance of the viral burden on
      neurologic consequences of HIV infection. 

PMID- 25750072
TI  - The effects of antiretroviral treatment initiation on cognition in HIV-infected
      individuals with advanced disease in Pune, India.
AB  - There has been a reduction in the most severe cases of HIV-associated
      neurocognitive disorders (HAND) with advances in antiretroviral treatment (ART).
      But the prevalence of milder forms of HAND still remains high. Data from
      systematically conducted studies on the effects of ART on cognition are scanty in
      India, where HIV-1 clade C is prevalent. The purpose of the present study was to
      assess the effect of antiretroviral therapy in HIV-seropositive (HIV+)
      individuals (n = 92) with CD4 cell counts <200 cells/mm(3). The overall and
      domain-specific levels of cognitive functioning were determined using a locally
      recruited normative sample, and a change in neurocognitive functioning at the 1
      year follow-up visit was analyzed. Results revealed cognitive impairment in 44.6
      % of the HIV+ group at baseline. At the 1-year follow-up, the group showed
      significant improvement in the Learning domain (p < 0.05). HIV+ individuals
      showing improvement in the global cognitive scores had a significantly lower
      baseline CD4 cell count compared to others. Overall, the degree of improvement
      associated with the magnitude of rise in CD4 suggests the possibility that early,
      mild subclinical deficits may also benefit from treatment.

PMID- 25750073
TI  - [Risk stratification for sudden cardiac death in ischemic heart disease.
      Programmed ventricular stimulation].
AB  - Programmed ventricular stimulation was used extensively in the 1970s and has
      markedly improved our knowledge about the electrophysiological mechanisms of
      reentrant ventricular arrhythmias. In numerous observational but also randomized
      studies, it was shown that the induction of a monomorphic ventricular tachycardia
      by programmed ventricular stimulation was associated with an increased risk of
      spontaneous ventricular tachycardia or even sudden cardiac death in the future.
      Despite these results and the guidelines of ACC and ESC recommending the use of
      programmed ventricular stimulation in patients with recent and remote myocardial
      infarction, reduced ejection fraction, and complex ventricular arrhythmias or
      syncope, programmed ventricular stimulation is only seldom used and does not play
      a relevant role in clinical practice today. The purpose of this overview is to
      reevaluate the importance of programmed ventricular stimulation for the risk
      evaluation of patients with ischemic heart disease in consideration of the
      current literature. 

PMID- 25750074
TI  - Optimizing HLA matching in a highly sensitized pediatric patient using ABO
      incompatible and paired exchange kidney transplantation.
AB  - BACKGROUND: Kidney transplantation is the treatment of choice for end-stage renal
      disease. However, since pediatric patients have long projected life-years, it is
      also optimal for them to get well-matched transplants to minimize long-term
      sensitization. In North America, pediatric kidney transplantation is largely
      dependent upon the use of deceased donor organs, making it challenging to
      identify timely, well-matched transplants. Pediatric recipients may have willing
      living donors who are either HLA- or ABO-incompatible (ABOi); therefore, one
      solution is to utilize ABOi transplants and paired exchange programs to enhance
      HLA matching and living donation. CASE-DIAGNOSIS/TREATMENT: We adopted this
      approach for a highly sensitized patient with cPRA 90%, who received a successful
      ABOi paired exchange transplant. The recipient received pre-transplant
      immunomodulation until an acceptable isohemagglutinin titer <1:8 was reached
      before transplantation. The patient was induced with anti-thymocyte globulin and
      maintained on steroid-based triple immunosuppression. Eighteen-month allograft
      function is excellent with an estimated glomerular filtration rate (eGFR) of
      83.53 ml/min/1.73 m(2). The patient did not develop de novo donor-specific HLA
      antibodies or have any episodes of acute rejection CONCLUSIONS: This case
      highlights the safety and efficacy of using paired exchange in combination with
      ABOi transplants in pediatric kidney transplantation to optimize HLA matching,
      minimize wait times, and enhance allograft survival.

PMID- 25750076
TI  - Consequences of the Chicago DSD Consensus: A Personal Perspective.
AB  - A decade has passed since the Chicago Consensus meeting was convened to consider
      how to improve the management of individuals and their families with an intersex
      disorder. It is apposite to review, from an individual perspective, what impact
      the Consensus has had on clinical practice and research. Emphasis is placed on
      nomenclature and DSD classification, multidisciplinary team working, striving to
      reach a causative diagnosis for DSD, the value of uniformity of collective case
      registries for rare conditions, and the potential for meaningful clinical outcome
      studies and basic scientific research. The impact of the Consensus can be gauged
      objectively by an exponential increase in DSD-related publications in the medical
      and scientific literature and organisation of numerous national and international
      meetings. Psychologists and social scientists have embraced the subject area and
      enhanced the holistic approach to management of DSD. Much needs to be done to
      improve diagnosis, and to identify measures to predict outcome that can be used
      both in sex assignment decision-making and to improve the quality of life for
      young adults with DSD. Though challenging, these goals are attainable through
      specialist multidisciplinary clinics working at local level and the DSD community
      at large, collaborating at national and international levels to tap the data
      resources now being developed. 

PMID- 25750075
TI  - Kidney transplantation in children with decreased left ventricular systolic
      function: a Midwest Pediatric Nephrology Consortium study.
AB  - BACKGROUND: Left ventricular (LV) systolic dysfunction is a relatively uncommon
      but serious complication of pediatric chronic kidney disease, and may be related
      to uremia and uncontrolled hypertension. There is limited information on the
      strategy for managing these children. In some cases, combined heart-kidney
      transplant may be considered or kidney transplant delayed until cardiac function
      improves. It is unknown whether these patients are at increased risk for poor
      outcomes after kidney transplantation. METHODS: We conducted a retrospective,
      multicenter study on the outcomes of children with severe and symptomatic
      cardiomyopathy who underwent kidney transplantation. RESULTS: Eleven patients
      receiving maintenance dialysis with systolic dysfunction underwent kidney
      transplantation without simultaneous heart transplant. Nine patients had
      congestive heart failure in the pre-transplant period. There were no identified
      complications post-transplant related to the underlying cardiac dysfunction. LV
      systolic function normalized in all patients and the mean shortening fraction
      increased from 19.0 +/- 4.6 % to 32.0 +/- 4.4 % (p < 0.0001). CONCLUSIONS: Kidney
      transplantation should be considered for children receiving maintenance dialysis
      with severe LV dysfunction.

PMID- 25750077
TI  - Increased Risk of Unfavorable Metabolic Outcome in Patients with Clinically
      Nonfunctioning Pituitary Adenomas.
AB  - The aim of this study was to investigate atherosclerotic risk markers in women
      with clinically nonfunctioning pituitary adenomas (CNFAs). Records of 47 women
      with CNFAs and 73 healthy women who were treated as outpatients between January
      2010 and March 2014 were evaluated retrospectively. All study data were obtained
      from file records. Lipid parameters, mean platelet volume (MPV), total
      testosterone (TT), androstenedione (AS), and dehydroepiandrostenedione sulfate
      (DHEAS) were recorded. Insulin resistance (IR) was calculated with homeostatic
      model assessment-insulin resistance (HOMA-IR). Among the atherosclerotic risk
      markers, the HOMA-IR and AS levels were higher in patients with CNFAs than in
      healthy subjects (p=0.003, p=0.021, respectively). A positive correlation between
      AS and insulin/HOMA-IR levels was found among the metabolic parameters in the
      patients with CNFAs (p=0.001, r=0.550, p=0.004, r=0.498, respectively). The data
      showed that patients with CNFAs had high atherosclerotic risk markers such as
      insulin resistance and hyperandrogenemia. Insulin resistance may also cause
      hyperandrogenemia in patients with CNFAs. 

PMID- 25750078
TI  - Integration of Peripheral and Glandular Regulation of Triiodothyronine Production
      by Thyrotropin in Untreated and Thyroxine-Treated Subjects.
AB  - The objective of the study was to evaluate the roles of central and peripheral T3
      regulation. In a prospective study involving 1,796 patients, the equilibria
      between FT3 and TSH were compared in untreated and L-T4-treated patients with
      varying functional states, residual thyroid secretory capacities and magnitudes
      of TSH stimulation. T3 concentrations were stable over wide variations in TSH
      levels (from 0.2 to 7 mU/l) and endogenous T4 production in untreated patients,
      but unbalanced in L-T4-treated athyreotic patients where T3 correlated with
      exogenous T4 supply. T3 stability was related to TSH-stimulated deiodinase
      activity by clinical observation, as predicted by theoretical modelling.
      Deiodinase activity in treated patients was reduced due to both diminished
      responsiveness to TSH and lack of thyroidal capacity. Deiodinase activity was
      increased in high thyroid volume, compared to lower volumes in euthyroid patients
      (<5 ml, p<0.001). While deiodinase differed between euthyroid and subclinically
      hypothyroid patients in high volume, 26.7 nmol/s (23.6, 29.2), n=214 vs. 28.9
      nmol/s (26.7, 31.5), n=20, p=0.02, it was equivalent between the 2 functional
      groups in low volume, 23.3 nmol/s (21.3, 26.1), n=117 vs. 24.6 nmol/s (22.2,
      27.5), n=38, p=0.22. These findings suggest that the thyroid gland and peripheral
      tissues are integrated in the physiological process of T3 homeostasis in humans
      via a feed-forward TSH motif, which coordinates peripheral and central regulatory
      mechanisms. Regulatory and capacity deficiencies collectively impair T3
      homeostasis in L-T4-treated patients.

PMID- 25750079
TI  - The Influence of Intranasal Insulin on Hypothalamic-Pituitary-Thyroid Axis in
      Normal and Diabetic Rats.
AB  - The functions of hypothalamic-pituitary-thyroid axis are attenuated in type 1
      diabetes mellitus due to insulin deficiency. The use of intranasally administered
      insulin is of considerable interest for treatment of diabetes and cognitive
      disorders, but its effect on the thyroid system has not been investigated yet. We
      studied the influence of long-term treatment with intranasal insulin on the
      hypothalamic-pituitary-thyroid axis of nondiabetic rats and diabetic animals with
      streptozotocin models of acute and mild type 1 diabetes mellitus. This treatment
      was carried out for 28 days in acute (daily does of 0.3, 0.6, and 1.5 IU of
      insulin per rat) and for 135 days in mild diabetes (daily dose of 0.45 IU/rat).
      Nondiabetic rats were treated in a similar manner. Intranasal insulin in both
      models of diabetes resulted in the improvement of thyroid status; manifested as
      increase of thyroid hormones levels and restoration of response to thyroliberin.
      In acute diabetes, a daily dose of 0.6 IU/rat was the most effective. Twenty
      eight days treatment of nondiabetic rats with intranasal insulin at a dose of 0.3
      IU/rat resulted in a significant increase of free and total thyroxine levels.
      Longer treatment of rats with mild diabetes and nondiabetic animals significantly
      increased thyrotropin level. Thus, long-term intranasal insulin treatment
      restored the hypothalamic-pituitary-thyroid axis function in type 1 diabetes, but
      led to a significant increase in the thyrotropin level, which must be considered
      when designing a strategy for the use of intranasal insulin in clinical
      applications. 

PMID- 25750080
TI  - Adolescents with Disorders of Sex Development (DSD)--Lost in Transition?
AB  - Children with chronic illnesses face multiple challenges as they mature into
      adulthood, which relate to independence, access to care, and changes in care
      providers. The scope and magnitude of these problems is amplified in children
      with disorders of sex development (DSD). In these children, the normal
      progression of pubertal events can be early, late, contrasexual,
      pharmacologically assisted, or some combination of these features. The diagnosis
      of DSD can occur in childhood, which gives the family some time to prepare for
      future events, but in other cases, the diagnosis is made during adolescence as
      the condition becomes apparent. This article discusses the difficulties these
      children and their families face during adolescence, provides an overview of the
      transitioning process, and uses a few conditions as examples to illustrate
      particular aspects. 

PMID- 25750081
TI  - Pick of the year 2014.

PMID- 25750082
TI  - A putative low-molecular-mass penicillin-binding protein (PBP) of Mycobacterium
      smegmatis exhibits prominent physiological characteristics of DD-carboxypeptidase
      and beta-lactamase.
AB  - DD-carboxypeptidases (DD-CPases) are low-molecular-mass (LMM) penicillin-binding
      proteins (PBPs) that are mainly involved in peptidoglycan remodelling, but little
      is known about the dd-CPases of mycobacteria. In this study, a putative DD-CPase
      of Mycobacterium smegmatis, MSMEG_2433 is characterized. The gene for the
      membrane-bound form of MSMEG_2433 was cloned and expressed in Escherichia coli in
      its active form, as revealed by its ability to bind to the Bocillin-FL
      (fluorescent penicillin). Interestingly, in vivo expression of MSMEG_2433 could
      restore the cell shape oddities of the septuple PBP mutant of E. coli, which was
      a prominent physiological characteristic of DD-CPases. Moreover, expression of
      MSMEG_2433 in trans elevated beta-lactam resistance in PBP deletion mutants
      (DeltadacAdacC) of E. coli, strengthening its physiology as a dd-CPase. To
      confirm the biochemical reason behind such physiological behaviours, a soluble
      form of MSMEG_2433 (sMSMEG_2433) was created, expressed and purified. In
      agreement with the observed physiological phenomena, sMSMEG_2433 exhibited DD
      CPase activity against artificial and peptidoglycan-mimetic DD-CPase substrates.
      To our surprise, enzymic analyses of MSMEG_2433 revealed efficient deacylation
      for beta-lactam substrates at physiological pH, which is a unique characteristic
      of beta-lactamases. In addition to the MSMEG_2433 active site that favours dd
      CPase activity, in silico analyses also predicted the presence of an omega-loop
      like region in MSMEG_2433, which is an important determinant of its beta
      lactamase activity. Based on the in vitro, in vivo and in silico studies, we
      conclude that MSMEG_2433 is a dual enzyme, possessing both DD-CPase and beta
      lactamase activities.

PMID- 25750083
TI  - pspK gene prevalence and characterization of non-typable Streptococcus pneumonia
      isolates from Asian countries.
AB  - Recently, it has been reported that some non-typable (NT) Streptococcus
      pneumoniae isolates from Korea and other countries contained a novel gene pspK in
      the capsular polysaccharide synthesis (cps) locus. In this study, we investigated
      the presence of pspK in 120 NT S. pneumoniae isolates from 12 Asian countries;
      isolate characteristics were also examined. The presence of pspK was assayed by
      PCR. Clonality of NT S. pneumoniae isolates containing pspK was investigated by
      MLST and PFGE. Antimicrobial susceptibility testing was performed and the
      structure of pspK was also determined. Nineteen NT isolates (15.8 %) were
      identified as containing pspK: two isolates from Korea, four from Vietnam, two
      from Hong Kong, eight from Thailand, and one each from Taiwan, the Philippines
      and Saudi Arabia. Seven isolates from Korea, Vietnam and Thailand were identified
      as ST1106, whereas just one or two belonged to ST310, ST393, ST10137, ST2754 or
      ST4136. All but one of the ST1106 NT isolates showed non-susceptibility to
      penicillin, and all isolates were resistant to cefuroxime, erythromycin,
      clindamycin and trimethoprim/sulfamethoxazole. The structure of pspK was similar
      amongst 20 isolates, which had a R1-R2-like region and a variable number of
      repeats in the repetitive region. However, one isolate (P05-11) from the
      Philippines lacked the R1-R2 region. NT S. pneumoniae isolates containing pspK
      were distributed across several Asian countries. Although MLST analysis suggested
      that most pspK-containing NT S. pneumoniae isolates may have emerged
      independently, ST1106 isolates with the selective advantage of antimicrobial
      resistance may have disseminated clonally throughout the countries. 

PMID- 25750085
TI  - Global and regional brain glucose metabolism decline after systemic chemotherapy.

PMID- 25750084
TI  - Volumetric assessment of recurrent or progressive gliomas: comparison between F
      DOPA PET and perfusion-weighted MRI.
AB  - PURPOSE: To compare the diagnostic information obtained with 6-[(18)F]-fluoro-L
      3,4-dihydroxyphenylalanine (F-DOPA) PET and relative cerebral blood volume (rCBV)
      maps in recurrent or progressive glioma. METHODS: All patients with recurrent or
      progressive glioma referred for F-DOPA imaging at our institution between May
      2010 and May 2014 were retrospectively included, provided that macroscopic
      disease was visible on conventional MRI images and that rCBV maps were available
      for comparison. The final analysis included 50 paired studies (44 patients).
      After image registration, automatic tumour segmentation of both sets of images
      was performed using the average signal in a large reference VOI including grey
      and white matter multiplied by 1.6. Tumour volumes identified by both modalities
      were compared and their spatial congruence calculated. The distances between F
      DOPA uptake and rCBV hot spots, tumour-to-brain ratios (TBRs) and normalized
      histograms were also computed. RESULTS: On visual inspection, 49 of the 50 F-DOPA
      and 45 of the 50 rCBV studies were classified as positive. The tumour volume
      delineated using F-DOPA (F-DOPAvol 1.6) greatly exceeded that of rCBV maps
      (rCBVvol 1.6). The median F-DOPAvol 1.6 and rCBVvol 1.6 were 11.44 ml (range 0 -
      220.95 ml) and 1.04 ml (range 0 - 26.30 ml), respectively (p < 0.00001). Overall,
      the median overlapping volume was 0.27 ml, resulting in a spatial congruence of
      1.38 % (range 0 - 39.22 %). The mean hot spot distance was 27.17 mm (+/-16.92
      mm). F-DOPA uptake TBR was significantly higher than rCBV TBR (1.76 +/- 0.60 vs.
      1.15 +/- 0.52, respectively; p < 0.0001). The histogram analysis showed that F
      DOPA provided better separation of tumour from background. In 6 of the 50 studies
      (12 %), however, physiological uptake in the striatum interfered with tumour
      delineation. CONCLUSION: The information provided by F-DOPA PET and rCBV maps are
      substantially different. Image interpretation is easier and a larger tumour
      extent is identified on F-DOPA PET images than on rCBV maps. The clinical impact
      of such differences needs to be explored in future studies.

PMID- 25750086
TI  - The anti-inflammatory secoiridoid glycosides from gentianae scabrae radix: the
      root and rhizome of Gentiana scabra.
AB  - Gentianae Scabrae Radix is a well-known traditional medicine that is used for the
      treatment of hepatitis, cholecystitis and inflammatory diseases. It consists
      mainly of secoiridoid glycosides, with representatives of gentiopicroside,
      sweroside and swertiamarin. In the present study, a chemical investigation of the
      CHCl3 extract of Gentianae Scabrae Radix derived from Gentiana scabra Bunge
      yielded seven new (1-7) and ten known (8-17) secoiridoid glycosides. Their
      structures were elucidated by extensive spectroscopic analyses and comparison
      with literature data. All 17 compounds were evaluated for their inhibitory
      effects against NO, IL-6 and TNF-alpha productions induced by lipopolysaccharide
      (LPS) in RAW264 cells. Among them, 8-epi-kingiside derivatives 1-3; kingiside
      derivatives 4, 5 and 10; and a sweroside derivative 6 showed inhibition activity
      against IL-6 production with IC50 values of 51.70-61.10 MUM, whereas sweroside
      derivatives 12 and 15-17 and a swertiamarin derivative 13 showed inhibition
      effects on both NO and IL-6 productions with IC50 values of 64.74-94.95 and 48.91
      75.45 MUM, respectively. All the compounds exhibited weak inhibitory activity
      (IC50 > 100 MUM) in a TNF-alpha bioassay. Finally, a primary structure-activity
      relationship of these secoiridoid glycosides is discussed. 

PMID- 25750087
TI  - PRKACA mutations in cortisol-producing adenomas and adrenal hyperplasia: a single
      center study of 60 cases.
AB  - OBJECTIVE: Cortisol excess due to adrenal adenomas or hyperplasia causes
      Cushing's syndrome. Recent genetic studies have identified a somatic
      PRKACA(L206R) mutation as a cause of cortisol-producing adenomas. We aimed to
      compare the clinical features of PRKACA-mutant lesions with those of CTNNB1
      mutations, and to search for similar mutations in unilateral hyperplasia or
      tumors co-secreting aldosterone. DESIGN, PATIENTS, AND METHODS: In this study, 60
      patients with cortisol excess who had adrenalectomies at our institution between
      1992 and 2013 were assessed, and somatic mutations were determined by Sanger
      sequencing. A total of 36 patients had overt Cushing's syndrome, the remainder
      were subclinical: 59 cases were adenomas (three bilateral) and one was classified
      as hyperplasia. Four tumors had proven co-secretion of aldosterone. RESULTS:
      Among cortisol-secreting unilateral lesions without evidence of co-secretion
      (n=52), we identified somatic mutations in PRKACA (L206R) in 23.1%, CTNNB1 (S45P,
      S45F) in 23.1%, GNAS (R201C) in 5.8%, and CTNNB1+GNAS (S45P, R201H) in 1.9%.
      PRKACA and GNAS mutations were mutually exclusive. Of the co-secreting tumors,
      two (50%) had mutations in KCNJ5 (G151R and L168R). The hyperplastic gland showed
      a PRKACA(L206R) mutation, while patients with bilateral adenomas did not have
      known somatic mutations. PRKACA-mutant lesions were associated with younger age,
      overt Cushing's syndrome, and higher cortisol levels vs non-PRKACA-mutant or
      CTNNB1-mutant lesions. CTNNB1 mutations were more significantly associated with
      right than left lesions. CONCLUSIONS: PRKACA(L206R) is present not only in
      adenomas, but also in unilateral hyperplasia and is associated with more severe
      autonomous cortisol secretion. Bilateral adenomas may be caused by yet-unknown
      germline mutations.

PMID- 25750088
TI  - Kangiella chungangensis sp. nov. isolated from a marine sand.
AB  - A Gram-negative bacterium, designated CAU 1040(T), which was isolated from marine
      sand obtained from Jeju Island in South Korea, was characterized as an aerobic
      rod-shaped organism that that was non-motile, non-spore-forming and halophilic.
      The bacterium grew optimally at 37  degrees C, at pH 8, and in the presence of 2%
      (w/v) NaCl. The taxonomic classification of CAU 1040(T) was investigated using a
      polyphasic characterization approach. While phylogenetic analysis of the 16S rRNA
      gene sequence revealed that CAU 1040(T) belongs to the genus Kangiella, the
      strain exhibited only 94.4-95.4% sequence similarity to the previously described
      Kangiella species. Similar to other Kangiella species, Q-8 was the predominant
      ubiquionone and iso-C(15:0) was the major cellular fatty acid detected in strain
      CAU 1040(T). The predominant polar lipids identified were diphosphatidylglycerol,
      phosphatidylglycerol, and phosphatidylethanolamine. The G+C content of the CAU
      1040(T) genome was 45.3 mol%. The phylogenetic, physiological, biochemical and
      chemotaxonomic data obtained in this study indicate that strain CAU 1040(T)
      represents a novel species of the genus Kangiella, for which the name Kangiella
      chungangensis sp. nov. is hereby proposed. The type strain is CAU 1040(T) (KCTC
      42299(T), NBRC 110728(T)).

PMID- 25750089
TI  - Introduction to the Special Issue: Public Health Genetics and Genomics.
AB  - This special issue of the Journal of Genetic Counseling is dedicated to public
      health genetics and genomics. The seventeen papers featured in this issue span
      such topics as genetic counselors in public health roles, newborn screening,
      population screening, ethics, and health beliefs and behaviors. In this
      introduction to the special issue, we review some history of public health
      genetics and genomics, present the Centers for Disease Control and Prevention's
      "10 Essential Public Health Services" with associated genetics specific
      recommendations and priorities, and briefly overview how each article ties into
      the world of public health genetics and genomics. We hope this issue encourages
      genetic counselors to visualize their ever expanding and important roles in
      public health genetics and genomics, as well as their contributions to improving
      population health.

PMID- 25750090
TI  - One-year safety and quality of life outcomes in patients with atrial fibrillation
      on dronedarone: prospective, non-interventional study in German ambulatory care.
AB  - BACKGROUND AND AIMS: The multichannel blocker dronedarone is currently indicated
      for the maintenance of sinus rhythm after successful cardioversion in adult
      clinically stable patients with paroxysmal or persistent atrial fibrillation
      (AF), with careful monitoring of cardiac, hepatic and renal function. We aimed to
      investigate patients' quality of life (QoL) and tolerability and effectiveness of
      dronedarone under real life conditions. METHODS: In the 1-year prospective, non
      interventional IMPULS study, 161 office-based cardiologists, general
      practitioners and internists throughout Germany documented 549 patients with AF
      who were currently or newly prescribed dronedarone (safety set, SS). Of those,
      342 patients (full analysis set, FAS) provided data on QoL at baseline, 6 months
      and 12 months). RESULTS: Mean age of patients was 67.6/66.3 years; 53.0 %/57.3 %
      were men (SS/FAS). AF type at inclusion in the SS/FAS was paroxysmal in 71.9
      %/71.3 % and persistent in 26.0 %/26.6 % (missing in 2.0 %/2.0 %). The proportion
      of patients in sinus rhythm increased from 44.6 % at baseline to 70.2 % (SS). The
      mean value on the 100-point visual analogue scale (EuroQol EQ-5D) increased from
      62.3 +/- 17.1 at baseline by 11.4 +/- 18.7 points (FAS, p<0.0001). The AF-QoL
      Psychological Domain improved from 44.6 +/- 22.6 at baseline by 16.0 +/- 23.5
      points at 1 year (p<0.0001), the AF-QoL physical domain from 49.5 +/- 22.1 by
      10.9 +/- 22.5 points (p<0.0001), and the AF-QoL sexual domain from 61.8 +/- 27.1
      by 6.6 +/- 28.2 points (p<0.0001). In all, 136 patients (24.8 % of all patients
      in the safety set) had at least one adverse drug reaction (ADR) causally related
      to dronedarone. CONCLUSIONS: Various dimensions of quality of life of patients
      with AF were improved on dronedarone under clinical practice conditions. No
      previously unknown safety issues were noted.

PMID- 25750092
TI  - Erratum to: A robust asymmetry in loudness between rising- and falling-intensity
      tones.

PMID- 25750091
TI  - Roles of selenoprotein antioxidant protection in zebrafish, Danio rerio,
      subjected to dietary oxidative stress.
AB  - In vertebrates, selenium (Se) is an essential micronutrient for vertebrates that
      is involved in antioxidant protection and thyroid hormone regulation among other
      roles and functions through its incorporation into proteins, the selenoproteins.
      Long-chain polyunsaturated fatty acids, such as docosahexaenoic acid (DHA), are
      essential nutrients for fish although high dietary levels may lead to increased
      oxidative stress due to the high degree of unsaturation. The present study
      investigated the effects of Se supplementation on zebrafish, Danio rerio,
      oxidative status together with selenoprotein expression profiles when subjected
      to a high-DHA diet. Fish were fed for 8 weeks with one of the four experimental
      diets, containing high or low DHA in combination with or without organic Se (7
      mg/kg). Fish performance, Se content, fatty acid composition and TBARS of
      zebrafish were determined, as well as gene expression of selected selenoproteins
      in liver and muscle. The Se levels in whole fish reflected dietary content. High
      dietary DHA increased oxidative stress as indicated by reduced growth and high
      TBARS content, although Se supplementation reduced oxidation. The expression
      patterns of selenoproteins varied between liver and muscle with only deiodinase
      type II displaying a transcriptional response when high dietary Se was supplied.
      High dietary DHA decreased selenoprotein W expression in muscle and sps2
      expression in liver regardless of the dietary Se content. These data suggest that
      oxidative stress protection associated with a high dietary intake of Se may not
      be solely mediated by transcriptional changes in teleost selenoprotein
      expression. 

PMID- 25750093
TI  - Circulating levels of adiponectin, resistin, and visfatin after mud-bath therapy
      in patients with bilateral knee osteoarthritis.
AB  - Adipocytokines, including adiponectin, resistin, and visfatin may play an
      important role in the pathophysiology of osteoarthritis (OA). Spa therapy is one
      of the most commonly used non-pharmacological approaches for OA, but its
      mechanisms of action are not completely known. The aim of the present study was
      to assess whether a cycle of mud-bath therapy (MBT) influences the serum levels
      of adiponectin, resistin, and visfatin in patients with knee OA. As part of a
      prospective randomized, single blind-controlled trial evaluating the efficacy of
      MBT in knee OA, we included in this study 95 outpatients. One group (n = 49)
      received a cycle of MBT at the spa center of Chianciano Terme (Italy) in addition
      to the usual treatment, and one group (control group; n = 46) continued their
      regular care routine alone. Patients were assessed at basal time and at the end
      of the study (15 days) for clinical and biochemical parameters. Clinical
      assessments included spontaneous pain on a visual analog scale (VAS) score and
      the Western Ontario and McMaster Universities index (WOMAC) subscores for knee OA
      evaluated as total pain score (W-TPS), total stiffness score (W-TSS), and total
      physical function score (W-TPFS). Adiponectin, resistin and visfatin serum levels
      were assessed by enzyme immunoassay methods. At the end of the mud-bath therapy,
      serum adiponectin levels showed a significant decrease (p < 0.001), while no
      significant modifications were found in the control group at day 15. Serum
      resistin showed a significant decrease (p < 0.0001) in the MBT group at the end
      of the study and a significant increase in the control patients (p < 0.001). No
      significant modifications of visfatin were found in MBT. Furthermore, we tested
      the relationships between demographic and clinical parameters and adipocytokine
      concentrations measured in the MBT group at basal and at the end of the study. In
      conclusion, the present study shows that a cycle of MBT can modify serum levels
      of adiponectin and resistin but not the circulating levels of visfatin. In view
      of the recent evidences about the involvement of adiponectin and resistin in the
      pathogenesis and progression of OA, the decrease of these adipokines after mud
      bath therapy may play a protective role in the course of the disease. However, it
      remains to be clarified which of the mechanisms of action of MBT may have
      determined the changes in serum levels of adiponectin and resistin that we
      observed.

PMID- 25750094
TI  - [Riociguat: stimulator of soluble guanylate-cyclase. New mode of action for the
      treatment of pulmonary arterial and non operable chronic thromboembolic pulmonary
      hypertension].
AB  - Riociguat is the first clinically available soluble Guanylate-cyclase stimulator
      (sGC) and representative of a completely new class of drugs. Riociguat is
      approved for pulmonary arterial hypertension (PAH) and non-operable or
      recurrent/persistent chronic thromboembolic pulmonary hypertension (CTEPH).
      Moreover, Riociguat is currently under investigation for a wider spectrum of
      diseases. This article focusses on its mode of action and clinical trial data.
      Finally, based on these data, the status of approval, as well as the costs a
      proposal is given how Riociguat can be integrated in the current treatment of PAH
      and CTEPH.

PMID- 25750095
TI  - [Standardization of spirometry: 2015 update. Published by German Atemwegsliga,
      German Respiratory Society and German Society of Occupational and Environmental
      Medicine].
AB  - Spirometry is a simple test and considered the gold standard in lung function. An
      obstructive ventilatory defect is a disproportionate reduction of maximal airflow
      from the lung in relation to the maximal volume that can be displaced from the
      lung. It implies airway narrowing and is defined by a reduced FEV1/FVC ratio
      below the 5th percentile of the predicted value (lower limit of normal, LLN). A
      restrictive disorder may be suspected when vital capacity (FVC) is reduced and
      FEV1/FVC is normal. It is definitely proven, however, only by a decrease in TLC
      below the 5th percentile of predicted value (LLN). The measurement of TLC by body
      plethysmography is necessary to confirm or exclude a restrictive defect or
      hyperinflation of the lung when FVC is below the LLN. 2012 a task force of the
      ERS published new reference values based on 74,187 records from healthy non
      smoking males and females from 26 countries. The new reference equations for the
      3-95 age range are now available that include appropriate age-dependent mean
      values and lower limits of normal (LLN). This presentation aims at providing the
      reader with recommendations dealing with standardization and interpretation of
      spirometry.

PMID- 25750096
TI  - [Surgical staging of lung cancer].
AB  - Proper staging of lung cancer represents the basis for any stage-adapted and
      optimized treatment. This is today implemented in specialized centers mainly
      through the use of modern imaging methods and minimally-invasive measures.
      However, general thoracic surgery has a role not only in the therapeutic
      management of lung cancer, but offers additional staging information whenever
      endoscopic or interventional methods fail to achieve representative tissue
      biopsies of mediastinal lymph nodes or suspect lesions for conclusive diagnosis.
      The thoracic surgical armentarium comprises of cervical or extended
      mediastinoscopy, video-assisted mediastinal lymphadenectomy (VAMLA), anterior
      mediastinotomy (Chamberlain procedure) and video-thoracoscopy (VATS). Indications
      for any invasive diagnostic methods always have to respect a therapeutic benefit
      for the patient. 

PMID- 25750097
TI  - [Unmet need in asthma management and future treatment options].

PMID- 25750099
TI  - Clinical application of sonoelastography in thyroid, prostate, kidney, pancreas,
      and deep venous thrombosis.
AB  - This article reviews the clinical applications of current ultrasound elastography
      methods in non-hepatic conditions including thyroid nodules, prostate cancer,
      chronic kidney disease, solid renal lesions, pancreatic lesions, and deep vein
      thrombosis. Pathophysiology alters tissue mechanical properties via
      ultrastructural changes including fibrosis, increased cellularity, bleeding, and
      necrosis, creating a target biomarker, which can be imaged qualitatively or
      quantitatively with US elastography. US elastography methods can add information
      to conventional US methods and improve the diagnostic performance of conventional
      US in a range of disease processes.

PMID- 25750098
TI  - Giant Cell Tumor of the Larynx Treated by Surgery and Adjuvant Denosumab: Case
      Report and Review of the Literature.
AB  - Giant cell tumor of the larynx (GCTL) is a rare entity; only 34 cases have been
      reported in the literature. We report a case of GCTL in a 46 year-old male
      presenting clinical, radiographic, histological and therapeutic features.
      Previously reported cases are also reviewed. 

PMID- 25750100
TI  - Effect of embryo culture media on percentage of males at birth.
AB  - STUDY QUESTION: Does embryo culture medium influence the percentage of males at
      birth? SUMMARY ANSWER: The percentage of males delivered after ICSI cycles using
      G5TM medium was statistically significantly higher than after cycles where
      Global, G5TM PLUS, and Quinn's Advantage Media were used. WHAT IS KNOWN ALREADY:
      Male and female embryos have different physiologies during preimplantation
      development. Manipulating the energy substrate and adding growth factors have a
      differential impact on the development of male and female embryos. STUDY DESIGN,
      SIZE AND DURATION: This was a retrospective analysis of the percentage of males
      at birth, and included 4411 singletons born from fresh embryo transfer cycles
      between January 2011 and August 2013 at the Center for Reproductive Medicine of
      Third Hospital Peking University. PARTICIPANTS/MATERIALS, SETTING, AND METHODS:
      Only singleton gestations were included. Participants were excluded if
      preimplantation genetic diagnosis, donor oocytes and donor sperm were used. The
      database between January 2011 and August 2013 was searched with unique medical
      record number, all patients were present in the database with only one cycle.
      Demographics, cycle characteristics and the percentage of male babies in the four
      culture media groups were compared with analysis of variance or chi(2) tests.
      Multivariable logistic regression was done to determine the association between
      the sex at birth and culture media after adjusting for other confounding factors,
      including parental age, parental BMI, type of infertility, parity, number of
      embryos transferred, number of early gestational sacs, cycles with testicular
      sperm aspiration (TESA)/percutaneous epididymal sperm aspiration
      (PESA)/testicular sperm extraction (TESE), number of oocytes retrieved, cycles
      with blastocyst transfers, and gestational age within ICSI group. MAIN RESULTS
      AND THE ROLE OF CHANCE: Within the IVF group, the percentage of males at birth
      for G5TM, Global, Quinn's and G5TM PLUS media were comparable (P > 0.05);
      however, within the ICSI group, the percentage of male babies in cycles using
      G5TM(56.1%) was statistically significantly higher than in cycles that used
      Global (47.2%; P = 0.003), G5TM PLUS (47.7%; P = 0.005) or Quinn's media (45.0%;
      P = 0.009). There were no statistically significant differences in the percentage
      of males at birth between cycles that used Global, G5TM PLUS and Quinn's media (P
      > 0.05). Multivariable logistic regression indicated that culture media (G5TM
      versus Global, G5TM PLUS, and Quinn's) were significantly associated with the sex
      at birth (P = 0.008) after adjusting for parental age, parental BMI, type of
      infertility, parity, number of embryos transferred, number of early gestational
      sacs, cycles with TESA/PESA/TESE, number of oocytes retrieved, cycles with
      blastocyst transfers, and gestational age. LIMITATIONS AND REASONS FOR CAUTION:
      This study was not a randomized controlled trial and allocation of treatment
      cycles over the four media was not completely at random. Cigarette smoking was
      not included in the current study because this confounding factor was not
      registered in our database. Moreover, intra-variability of sperm selection
      between the five embryologists may directly affect the percentage of males. WIDER
      IMPLICATIONS OF THESE FINDINGS: Our study suggests that human embryogenesis
      responds differently to G5TM, Global, G5TM PLUS and Quinn's Advantage Medium.
      This finding can be generalized to other commercial culture media. STUDY
      FUNDING/COMPETING INTERESTS: National Natural Science Foundation of China for
      Young Scholars (81300483 and 81200466). The authors have no conflicts of interest
      to declare. TRIAL REGISTRATION NUMBER: Not applicable.

PMID- 25750101
TI  - Aberrant activation of signal transducer and activator of transcription-3 (STAT3)
      signaling in endometriosis.
AB  - STUDY QUESTION: Are STAT3 signaling molecules differentially expressed in
      endometriosis? SUMMARY ANSWER: Levels of phospho-STAT3 and HIF1A, its downstream
      signaling molecule, are significantly higher in eutopic endometrium from women
      with endometriosis when compared with women without the disease. WHAT IS KNOWN
      ALREADY: Endometriosis is an estrogen-dependent inflammatory condition.
      Interleukin 6 (IL-6) is an inflammatory survival cytokine known to induce
      prolonged activation of STAT3 via association with the IL-6 receptor. STUDY
      DESIGN, SIZE, DURATION: Cross-sectional measurements of STAT3 and HIF1A protein
      levels in eutopic endometrium from women with endometriosis versus those without.
      PARTICIPANTS/MATERIALS, SETTING, METHODS: Levels of phospho-STAT3 (pSTAT3) and
      HIF1A were examined in the endometrium of patients with and without endometriosis
      as well as in a non-human primate animal model using western blot and
      immunohistochemical analysis. MAIN RESULTS AND THE ROLE OF CHANCE: Levels of
      pSTAT3 were significantly higher in the eutopic endometrium from women with
      endometriosis when compared with women without the disease in both the
      proliferative and secretory phases. HIF1A is known to be stabilized by STAT3 and
      IL-6. Our immunohistochemistry results show abundant HIF1A expression within the
      eutopic endometrial epithelial cells of women with endometriosis. Furthermore,
      pSTAT3 and HIF1A proteins are co-localized in endometriosis. This aberrant
      activation of pSTAT3 and HIF1A is confirmed by sequential analysis of eutopic
      endometrium using a baboon animal model of induced endometriosis. Lastly, we
      confirmed this IL-6 induction of both STAT3 phosphorylation and HIF1A mRNA
      expression in Ishikawa human endometrial adenocarcinoma cell line. LIMITATIONS,
      REASONS FOR CAUTION: Ishikawa cancer cell line was used to study a benign
      disease. The peritoneal fluid contains various inflammatory cytokines in addition
      to IL-6 and so it is possible that other cytokines may affect the activity and
      expression of STAT3 signaling molecules. WIDER IMPLICATIONS OF THE FINDINGS: Our
      results imply that aberrant activation of STAT3 signaling plays an important role
      in the pathogenesis of endometriosis. Our findings could progress in our
      understanding of the etiology and pathophysiology of endometriosis and potential
      therapeutic interventions by targeted pharmacological. STUDY FUNDING/COMPETING
      INTERESTS: This work was supported by NIH R01 HD067721 (to S.L.Y and B.A.L) and
      NIH R01 HD057873 and American Cancer Society Research Grant RSG-12-084-01-TBG (to
      J.-W.J.). There are no conflicts of interest.

PMID- 25750102
TI  - Improving patient-centredness in partnership with female patients: a cluster RCT
      in fertility care.
AB  - QUESTION: What is the effect of a multifaceted intervention with participation of
      patients on improvement of patient-centredness in fertility care? SUMMARY ANSWER:
      A multifaceted intervention with participation of patients did not improve total
      patient-centredness scores provided by women in fertility care. WHAT IS KNOWN
      ALREADY: We should provide care that takes into account the preferences and needs
      of patients, i.e. patient-centred care. Especially infertile patients who suffer
      from a high emotional burden of treatment could benefit from a more patient
      centred approach in healthcare. However, the improvement of patient-centred care
      is still needed, because effective strategies to come to improvement are lacking.
      STUDY DESIGN, SIZE AND DURATION: A cluster RCT was performed within 32 Dutch
      fertility clinics, covering about one-third of all Dutch hospitals. After
      randomization, 16 clinics in the intervention group were exposed to a
      multifaceted improvement strategy for patient-centred fertility care for 1 year.
      This strategy comprised audit and feedback, educational outreach visits and
      patient-mediated interventions. The remaining 16 clinics in the control group
      performed care as usual. PARTICIPANTS/MATERIALS, SETTING AND METHODS: The
      clinics' levels of patient-centredness were measured, using the validated Patient
      centredness Questionnaire-Infertility (PCQ-Infertility). At baseline measurement,
      a total of 1620 women in couples undergoing fertility care (this included both
      male, female, mixed infertility and infertility of unknown cause) in one of the
      participating clinics were randomly selected to participate in the study and
      complete the questionnaire. For the after measurement, we randomly selected a
      comparable sample of 1565 women in infertile couples. Both women who had already
      started their treatment before the start of the study (67%) and women who started
      their treatment after the start of this study (33%) were included. To avoid bias,
      we only included the responses of non-pregnant respondents. MAIN RESULTS AND ROLE
      OF CHANCE: The final analysis involved 30 clinics. A total of 946 women (response
      58.4%) completed their questionnaire at baseline measurement and also a total of
      946 women (response 60.4%) at after measurement. After excluding the pregnant
      patients, respectively 696 and 730 questionnaires were eligible for analysis at
      baseline and after measurement. The total score of case-mix adjusted PCQ
      Infertility at after measurement did not differ significantly between the
      intervention and control group (B = 0.06; 95% confidence interval (CI) = -0.04
      0.15; P = 0.25). However, scores on the continuity of care subscale were
      significantly higher in the intervention group compared with the control group (B
      = 0.20; 95% CI = 0.00-0.40; P < 0.05). The addition of three interaction terms to
      the model had a significant impact: (i) being younger than 36 years, (ii)
      beginning treatment after the study had started and (iii) using complementary and
      alternative medicine. If women met all three conditions, the scores in the
      intervention group were on average 0.31 points higher compared with the control
      group (95% CI = 0.14-0.48; P = <0.001). LIMITATIONS, REASONS FOR CAUTION: Our
      response rates are sufficient, but the responses of many women are still lacking
      which might have biased our results. Furthermore, the PCQ-Infertility scores at
      baseline measurement were already reasonably high, which could have limited the
      effect of the multifaceted improvement strategy. Because we only included women
      in infertile couples in our study, we cannot draw conclusions on the effect of an
      improvement strategy for patient-centred fertility care for partners. WIDER
      IMPLICATION OF THE FINDINGS: A multifaceted intervention with participation of
      patients did not improve total patient-centredness scores, although some effect
      could be observed in specific groups of women and in specific dimensions of
      patient-centredness. These results can guide future research, in which we should
      focus more on personalized strategies and outcome measures. STUDY
      FUNDING/COMPETING INTERESTS: This work was supported by Merck Sharp & Dohme
      (MSD), The Netherlands. There are no competing interests. TRIAL REGISTRATION:
      Clinical Trials NCT01481064.

PMID- 25750103
TI  - AMH mutations with reduced in vitro bioactivity are related to premature ovarian
      insufficiency.
AB  - STUDY QUESTION: Could anti-Mullerian hormone (AMH) mutations be implicated in the
      development of idiopathic premature ovarian insufficiency (POI)? SUMMARY ANSWER:
      Three rare or unknown missense variants of the AMH gene were identified in a
      cohort of 55 POI patients; all three variants showed a drastically reduced in
      vitro bioactivity. WHAT IS KNOWN ALREADY: Genetic factors are implicated in 5-15%
      of cases of POI. However, only a few genes have been shown to be involved in its
      development. AMH inhibits the recruitment of primordial follicles in the ovary
      and defective or absent AMH leads to premature depletion of the primordial
      follicle pool in AMH null mice. STUDY DESIGN, SIZE, DURATION: The whole coding
      sequence and the exon-intron junction of the AMH gene was sequenced in a cohort
      of 55 POI patients recruited over a period of 8 years. The studied variants were
      also sequenced in 197 ethnically matched controls. PARTICIPANTS/MATERIALS,
      SETTING, METHODS: POI was defined as amenorrhea of more than 4 months with
      increased FSH before the age of 40. Patients with POI resulting from radio- or
      chemotherapy, surgery, chromosomal anomalies or FMR1 gene pre-mutation were
      excluded from the study. Recombinant human wild-type (wt) and mutated AMH
      proteins were produced in HEK293 T cells. KK-1 cells transfected with the AMH
      receptor type 2 (AMHR2) and a BMP responsive element coupled to a luciferase
      reporter vector were stimulated with different concentrations of wt AMH and the
      three tested variants. MAIN RESULTS AND THE ROLE OF CHANCE: The whole coding
      sequence of the AMH gene could be performed and analyzed for 50 POI patients: 16
      variants were found, including 6 missense variants from which 1 was unknown
      (R444H) and 2 were very rare (G264R and D288E). The variant D288E was also found
      in one of the patient's mother who also underwent POI at 32 years old. The
      stimulation of the AMHR2 assessed by the luciferase activity was drastically
      reduced for the three variants when compared with the wt AMH. LIMITATIONS,
      REASONS FOR CAUTION: The study is limited by a relatively small number of
      patients in the POI cohort. WIDER IMPLICATIONS OF THE FINDINGS: This is the first
      time that the bioactivity of AMH variants related to POI patients is tested in
      vitro. The functional study showed a drastic reduction of the protein activity
      for the three variants, supporting their contribution to the development of the
      ovarian insufficiency. The familial segregation further supports the implication
      of AMH in the development of POI. STUDY FUNDING/COMPETING INTERESTS: The study
      was performed thanks to funding from the 'Fondation Erasme'. No conflicts of
      interest are declared.

PMID- 25750104
TI  - Psychosocial development of full term singletons, born after preimplantation
      genetic diagnosis (PGD) at preschool age and family functioning: a prospective
      case-controlled study and multi-informant approach.
AB  - STUDY QUESTION: Do full term singletons born after preimplantation genetic
      diagnosis (PGD) differ in their psychosocial functioning from children born after
      intracytoplasmic sperm injection (ICSI) and spontaneous conceived controls (SC)?
      SUMMARY ANSWER: The psychosocial maturation process of 5-6-year-old PGD children
      is comparable between the three conception groups (PGD, ICSI and SC). WHAT IS
      ALREADY KNOWN: In general, a lot of research has been published regarding follow
      up of children born after artificial reproductive technologies (ART), which
      mainly is reassuring. But the ART population itself is marked by broad diversity
      [IVF, ICSI, gamete donation, preimplantation genetic screening (PGS) or PGD]
      which complicates comparisons. Some literature concerning the socio-emotional
      development of PGD/PGS children is available and it suggests a normal maturation
      process. However, the complex reality of PGD families (e.g. safety of the
      technique and psychological burden of genetic histories) asks for an exclusive
      PGD sample with matched control groups and a multi-informant approach. STUDY
      DESIGN, SIZE, DURATION: Between April 2011 and May 2013, the psychosocial
      wellbeing of preschoolers and their families born after PGD was assessed in a
      prospective case-controlled, matched follow-up study, with a multi-informant
      approach. PARTICIPANTS/MATERIALS, SETTING, METHODS: A group of 47 PGD, 50 ICSI
      and 55 SC 5-6-year-old children participated in a follow-up study performed at
      the Centre for Medical Genetics of the Universitair Ziekenhuis Brussel (UZ
      Brussel). Assessments took place in the hospital and in kindergartens. Children
      performed the Bene-Anthony family relations test (FRT), yielding their
      perceptions upon family relationships. Parents and teachers completed the child
      behaviour checklist (CBCL) and Caregiver Teacher Report Form (C-/TRF),
      respectively. Parental and family functioning were measured by the NEO-FFi, the
      parenting stress index (PSI), the Greenberger Work-Parenting Investment
      Questionnaire and the Marlowe-Crowne Social Desirability Scale (MCSDS).
      Statistical analysis was performed by using analysis of covariance (ANCOVA). MAIN
      RESULTS AND THE ROLE OF CHANCE: No differences were detected between the
      psychosocial development of PGD children and the control groups. Parents did not
      differ in reporting problem behaviour and they were stricter than teachers.
      Concerning family functioning the ART parents scored comparable with each other.
      PGD and ICSI mothers were emotionally more stable [NEO-FFi
      Neuroticism/emotionality: P = 0.013, eta(2) = 0.066; 95% confidence interval (CI)
      95% (0.003;0.148)]. They experienced less parental stress in general [PSI, Total
      stress: P = 0.001, eta(2) = 0.102, 95% CI (0.02;0.192)] and on different
      sublevels opposed to their SC counterparts. Yet ART mothers presented higher
      ratings on the NEO-FFi Conscientiousness [P = 0.011, eta(2) = 0.064; 95% CI
      (0.003;0.144)] indicating a higher feeling of competence and goal directedness.
      Mediation analysis confirmed: PGD and ICSI mothers who experienced less family
      stress were emotionally more stable. A power analysis indicated that a sample
      with 152 children is sufficient to detect a medium size effect with 80% power
      using ANCOVA. LIMITATIONS, REASONS FOR CAUTION: The current sample comprised only
      Dutch speaking Caucasians, hence conclusions should be drawn cautiously. Future
      research should include larger groups, prematures, multiples and children from
      different cultural backgrounds. WIDER IMPLICATIONS OF THE FINDINGS: This current
      research is the first to compare PGD preschoolers with matched controls. Concerns
      about the behavioural effects on the offspring should not inhibit the use of PGD.
      Furthermore, our findings suggest that on the long run ART procedures might
      enhance personal resources of women to cope with family stress. These findings
      are reassuring for women who might feel insecure and anxious during their ART
      trajectory. STUDY FUNDING/COMPETING INTERESTS: This research project gained
      funding from the OZR (a grant by the Research group of the Vrije Universiteit
      Brussel), the FWO (Fonds Wetenschappelijk Onderzoek) and the Wetenschappelijk
      Fonds Willy Gepts. The UZ Brussel and the Centre of Medical Genetics received
      funding from pharmaceutical firms for data collection. UZ Brussel and the Centre
      for Medical Genetics have received many educational grants for organizing the
      data collection, from IBSA, Ferring, Organon, Shering-Plough, Merck and Merck
      Belgium. M.B. has received consultancy and speaker's fees from Organon, Serono
      Symposia and Merck. The other authors have no competing interests. TRIAL
      REGISTRATION NUMBER: not applicable.

PMID- 25750106
TI  - Breathing biofeedback as an adjunct to exposure in cognitive behavioral therapy
      hastens the reduction of PTSD symptoms: a pilot study.
AB  - Although trauma-focused cognitive behavioral therapy (TF-CBT) with exposure is an
      effective treatment for posttraumatic stress disorder (PTSD), not all patients
      recover. Addition of breathing biofeedback to exposure in TF-CBT is suggested as
      a promising complementary technique to improve recovery of PTSD symptoms.
      Patients (n = 8) with chronic PTSD were randomized to regular TF-CBT or TF-CBT
      with complementary breathing biofeedback to exposure. PTSD symptoms were measured
      before, during and after TF-CBT with the Impact of Event Scale-Revised. The
      results show that breathing biofeedback is feasible and can easily be
      complemented to TF-CBT. Although PTSD symptoms significantly decreased from pre
      to post treatment in both conditions, there was a clear trend towards a
      significantly faster (p = .051) symptom reduction in biofeedback compared to
      regular TF-CBT. The most important limitation was the small sample size. The
      hastened clinical improvement in the biofeedback condition supports the idea that
      breathing biofeedback may be an effective complementary component to exposure in
      PTSD patients. The mechanism of action of breathing biofeedback may relate to
      competing working memory resources decreasing vividness and emotionality, similar
      to eye movement desensitization and reprocessing. Future research is needed to
      examine this.

PMID- 25750105
TI  - Endometrial stromal fibroblasts from women with polycystic ovary syndrome have
      impaired progesterone-mediated decidualization, aberrant cytokine profiles and
      promote enhanced immune cell migration in vitro.
AB  - STUDY QUESTION: Do endometrial stromal fibroblasts (eSF) in women with polycystic
      ovary syndrome (PCOS) (eSFpcos) exhibit altered estrogen and/or progesterone (P4)
      responses, which may explain some of the adverse reproductive outcomes and
      endometrial pathologies in these women? SUMMARY ANSWER: In vitro, eSF from women
      with PCOS exhibit an aberrant decidualization response and concomitant changes in
      pro-inflammatory cytokine, chemokine and matrix metalloproteinase (MMP) release
      and immune cell chemoattraction. In vivo these aberrations may result in
      suboptimal implantation and predisposition to endometrial cancer. WHAT IS KNOWN
      ALREADY: The endometrium in women with PCOS has several abnormalities including
      progesterone (P4) resistance at the gene expression level, likely contributing to
      subfertility, pregnancy complications and increased endometrial cancer risk in
      PCOS women. STUDY DESIGN, SIZE, DURATION: Prospective, university-based, case
      control, in vitro study. PARTICIPANTS/MATERIALS, SETTING, METHODS: Cultures of
      eSFPCOS (n = 12, Rotterdam and NIH criteria) and eSFControl (Ctrl) (n = 6,
      regular cycle length, no signs of hyperandrogenism) were treated with vehicle,
      estradiol (E2, 10 nM) or E2P4 (10 nM/1 MUM) for 14 days. Progesterone receptor
      (PGR) mRNA was assessed with quantitative real-time PCR (qRT-PCR) and eSF
      decidualization was confirmed by insulin-like growth factor-binding protein-1
      (IGFBP-1) transcript and protein expression. Fractalkine (CX3CL1), granulocyte
      macrophage colony-stimulating factor (GM-CSF), interleukin (IL) 6, 8 and 11,
      macrophage chemoattractant protein (MCP) 1 and 3, CCL5 (RANTES) and MMPs (MMP1,
      2, 3, 7, 9, 10 and 12) were measured in conditioned media by Luminex multiplex
      assays, and chemotactic activity of the conditioned media was tested in a
      migration assay using CD14+ monocyte and CD4+ T-cell migration assay. Effects of
      IL-6 (0.02, 0.2, 2 or 20 ng/ml) or IL-8 (0.04, 0.4, 4, or 40 ng/ml) or
      combination (0.2 ng/ml IL-6 and 4.0 ng/ml IL-8) on 14-d decidualization were also
      tested. ANOVA with pre-planned contrasts was used for statistical analysis. MAIN
      RESULTS AND THE ROLE OF CHANCE: Hormonal challenge with E2P4 to induce
      decidualization revealed two distinct subsets of eSFPCOS. Eight eSFPCOS (dPCOS)
      and all eSFCtrl (dCtrl) cultures showed a normal decidualization response to E2P4
      as determined by morphology and IGFBP-1 secretion. However, 4 eSFPCOS cultures
      showed blunted decidualization (ndPCOS) in morphological assessment and low IGFBP
      1 levels even though all three groups exhibited normal estrogen-mediated increase
      in PGR expression. Interestingly dPCOS had decreased IL-6 and GM-SCF secretion
      compared with dCtrl, whereas the ndPCOS cultures showed increased IL-6 and 8,
      MCP1, RANTES and GM-CSF secretion at base-line and/or in response to E2 or E2P4
      compared with dCtrl and/or dPCOS. Furthermore, even though PGR expression was
      similar in all three groups, P4 inhibition of MMP secretion was attenuated in
      ndPCOS resulting in higher MMP2 and 3 levels. The conditioned media from ndPCOS
      had increased chemoattractic activity compared with dCtrl and dPCOS media.
      Exogenously added IL-6 and/or 8 did not inhibit decidualization in eSFCtrl
      indicating that high levels of these cytokines in ndPCOS samples were not likely
      a cause for the aberrant decidualization. LIMITATIONS, REASONS FOR CAUTION: This
      is an in vitro study with a small sample size, utilizing stromal cell cultures
      from proliferative and secretory phase endometrium. The effect of PCOS on
      endometrial epithelium, another major histoarchitectural cell compartment of the
      endometrium, was not evaluated and should be considered in future studies.
      Furthermore, results obtained should also be confirmed in a larger data set and
      with mid/late secretory phase in vivo samples and models. WIDER IMPLICATIONS OF
      THE FINDINGS: The alterations seen in ndPCOS may contribute to endometrial
      dysfunction, subfertility and pregnancy complications in PCOS women. The results
      emphasize the importance of understanding immune responses related to the
      implantation process and normal endometrial homeostasis in women with PCOS. STUDY
      FUNDING/COMPETING INTERESTS: Sigrid Juselius Foundation, Academy of Finland,
      Finnish Medical Foundation, Orion-Farmos Research Foundation (to T.T.P.), the NIH
      Eunice Kennedy Shriver National Institute of Child Health and Human Development
      (NICHD) U54HD 055764-07 Specialized Cooperative Centers Program in Reproduction
      and Infertility Research (to L.C.G.), the NICHD the Ruth L. Kirschstein National
      Research Service Awards grant 1F32HD074423-03 (to J.C.C.). The authors have no
      competing interests.

PMID- 25750107
TI  - Assessment of Body Mass Index, Sugar Sweetened Beverage Intake and Time Spent in
      Physical Activity of American Indian Children in Oklahoma.
AB  - American Indian (AI) children have a combined overweight and obesity prevalence
      of 53%. Behaviors that contribute to obesity, such as sugar sweetened beverage
      (SSB) intake and time spent in physical activity (PA), have been poorly explored
      in this population. The purpose of this study is to report body mass index (BMI),
      SSB intake, and time spent in PA of 7-to-13-year-old AI children who reside in
      rural and urban areas in Oklahoma. Cross-sectional survey study. Self-reported
      SSB intake in the last month, and time spent in PA were collected via
      questionnaires. Height and weight were professionally measured. The sample
      included 124 7-to-13-year-old AI children who attended a diabetes prevention
      summer camp in 2013. BMI percentile, overweight and obesity prevalence, SSB
      intake, time spent in PA, and number of participants meeting the Physical
      Activity Guidelines for Americans. Descriptive characteristics for BMI
      percentile, overweight and obesity, SSB intake, time spent in PA, and meeting PA
      recommendations were calculated using means, standard deviations, and
      frequencies. Independent t test and Chi square analyses were used to test for
      gender differences. Participants were 10.2 +/- 1.5 years old and 57% female.
      Sixty-three percent were overweight or obese. Children consumed 309 +/- 309
      kcal/day of SSB and spent 4.4 +/- 3.8 h per week in moderate-to-vigorous PA.
      Approximately 32% met the 2008 Physical Activity Guidelines for Americans. No
      gender differences were observed. The prevalence of overweight and obesity was
      higher than previously reported in a similar population, and higher than that of
      US children in the general population. SSB intake and physical activity levels
      were also found to be higher in this group than in the general population.

PMID- 25750108
TI  - The Male Factor: Human Papillomavirus (HPV) and HPV4 Vaccine Acceptance Among
      African American Young Men.
AB  - The Human Papillomavirus (HPV) is one of the most prevalent sexually transmitted
      infections (STD) in the United States. In the U.S., racial and ethnic minorities
      are disproportionality affected by STDs. In 2009 the Food and Drug Administration
      approved the HPV4 vaccine for young men. It is necessary to understand African
      American young men's HPV knowledge, health beliefs, and perceived risk in
      relation to HPV4 vaccine acceptance. To date, there remains paucity in the
      literature regarding African American young men's HPV knowledge and HPV4 vaccine
      acceptance. The current study was a non-probability convenience sample of 68
      African American college students. This study was part of a larger project of
      HPV4 vaccine acceptance. Participants completed a 68-item questionnaire about
      personal characteristics, HPV, and the HPV4 vaccine. A majority of the young men
      had heard about HPV (85%, n = 58), however, only 38% (n = 26) new about the HPV4
      vaccine for women. Only 12.2% (n = 9) of the respondents knew of an HPV4 vaccine
      for men. The top three barriers to HPV4 vaccination were that insurance would not
      cover the vaccine; they would have to pay a lot for the vaccine and worrying that
      the vaccine is not safe. Study findings suggest that HPV and HPV4 education
      programs, and low or no cost HPV4 vaccinations for African American young men are
      needed.

PMID- 25750109
TI  - Interim results of pleurectomy/decortication and intraoperative intrapleural
      hyperthermic cisplatin perfusion for patients with malignant pleural mesothelioma
      intolerable to extrapleural pneumonectomy.
AB  - OBJECTIVE: Surgical procedure for malignant pleural mesothelioma (MPM) remains
      controversial. We reviewed our protocol including pleurectomy/decortication (P/D)
      for patients with malignant pleural mesothelioma who were intolerable to
      extrapleural pneumonectomy (EPP). PATIENTS AND METHODS: From June 2010 to April
      2014, 14 patients with MPM were intended to treat with multimodality therapy
      including surgery. Four patients who were intolerable to EPP received a protocol
      consisting of P/D and intraoperative intrapleural hyperthermic cisplatin
      perfusion, followed by systemic chemotherapy. Ten patients received trimodality
      treatment of EPP, systemic chemotherapy, and intensity modulated radiation
      therapy for hemithorax. Surgical outcomes of acute operative results and interim
      survivals were examined and compared between the groups. RESULTS: All patients
      obtained macroscopic complete resection and received multimodality treatment in
      P/D and EPP groups. Operation time was longer in P/D group; however, there were
      no differences in ICU stays or hospitalizations. Four patients in P/D group and
      seven patients in EPP group experienced postoperative complications; however,
      there was no operative morality. EPP group suffered from cardiac complications
      and P/D group had prolonged airleak. Full walk recovery was obtained earlier in
      P/D group. One patient in P/D group had a local recurrence 11 months after
      surgery, while the other three patients survived 23-41 months with no evidence of
      diseases. CONCLUSIONS: P/D and intraoperative intrapleural cisplatin perfusion
      achieved a favorable macroscopic resection in patients with MPM who were
      intolerable to EPP. Postoperative complications were manageable and survival
      could be promising. Further study warrants with a larger number of patients.

PMID- 25750110
TI  - Lumbar lordosis and sacral slope in lumbar spinal stenosis: standard values and
      measurement accuracy.
AB  - STUDY DESIGN: Radiological study. PURPOSE: To asses standard values, intra- and
      interobserver reliability and reproducibility of sacral slope (SS) and lumbar
      lordosis (LL) and the correlation of these parameters in patients with lumbar
      spinal stenosis (LSS). METHODS: Anteroposterior and lateral X-rays of the lumbar
      spine of 102 patients with LSS were included in this retrospective, radiologic
      study. Measurements of SS and LL were carried out by five examiners.
      Intraobserver correlation and correlation between LL and SS were calculated with
      Pearson's r linear correlation coefficient and intraclass correlation
      coefficients (ICC) were calculated for inter- and intraobserver reliability. In
      addition, patients were examined in subgroups with respect to previous surgery
      and the current therapy. RESULTS: Lumbar lordosis averaged 45.6 degrees  (range
      2.5 degrees -74.9 degrees ; SD 14.2 degrees ), intraobserver correlation was
      between Pearson r = 0.93 and 0.98. The measurement of SS averaged 35.3 degrees 
      (range 13.8 degrees -66.9 degrees ; SD 9.6 degrees ), intraobserver correlation
      was between Pearson r = 0.89 and 0.96. Intraobserver reliability ranged from
      0.966 to 0.992 ICC in LL measurements and 0.944-0.983 ICC in SS measurements.
      There was an interobserver reliability ICC of 0.944 in LL and 0.990 in SS.
      Correlation between LL and SS averaged r = 0.79. No statistically significant
      differences were observed between the analyzed subgroups. CONCLUSION: Manual
      measurement of LL and SS in patients with LSS on lateral radiographs is easily
      performed with excellent intra- and interobserver reliability. Correlation
      between LL and SS is very high. Differences between patients with and without
      previous decompression were not statistically significant.

PMID- 25750111
TI  - Lung Infarction Following Pulmonary Embolism: A Comparative Study on Clinical
      Conditions and CT Findings to Identify Predisposing Factors.
AB  - PURPOSE: The aim of this study was to identify factors predisposing to lung
      infarction in patients with pulmonary embolism (PE). MATERIALS AND METHODS: We
      performed a retrospective analysis on 154 patients with the final diagnosis of PE
      being examined between January 2009 and December 2012 by means of a Toshiba
      Aquilion 64 CT scanner. The severity of clinical symptoms was defined by means of
      a clinical index with 4 classes. The pulmonary clot load was quantified using a
      modified severity index of PE as proposed by Miller. We correlated several
      potential predictors of pulmonary infarction such as demographic data, pulmonary
      clot burden, distance of total vascular obstruction and pleura, the presence of
      cardiac congestion, signs of chronic bronchitis or emphysema with the occurrence
      of pulmonary infarction. RESULTS: Computed tomography revealed 78 areas of
      pulmonary infarction in 45/154 (29.2 %) patients. The presence of infarction was
      significantly higher in the right lung than in the left lung (p < 0.001). We
      found no correlation between pulmonary infarction and the presence of
      accompanying malignant diseases (r = -0.069), signs of chronic bronchitis (r = 
      0.109), cardiac congestion (r = -0.076), the quantified clot burden score (r =
      0.176), and the severity of symptoms (r = -0.024). Only a very weak negative
      correlation between the presence of infarction and age (r = -0.199) was seen.
      However, we could demonstrate a moderate negative correlation between the
      distance of total vascular occlusion and the occurrence of infarction (r = 
      0.504). CONCLUSION: Neither cardiac congestion nor the degree of pulmonary
      vascular obstruction are main factors predisposing to pulmonary infarction in
      patients with PE. It seems that a peripheral total vascular obstruction more
      often results in infarction than even massive central clot burden.

PMID- 25750112
TI  - Prenatal radiation exposure: dose calculation.
AB  - The unborn child requires special protection. In this context, the indication for
      an X-ray examination is to be checked critically. If thereupon radiation of the
      lower abdomen including the uterus cannot be avoided, the examination should be
      postponed until the end of pregnancy or alternative examination techniques should
      be considered. Under certain circumstances, either accidental or in unavoidable
      cases after a thorough risk assessment, radiation exposure of the unborn may take
      place. In some of these cases an expert radiation hygiene consultation may be
      required. This consultation should comprise the expected risks for the unborn
      while not perturbing the mother or the involved medical staff. For the risk
      assessment in case of an in-utero x-ray exposition deterministic damages with a
      defined threshold dose are distinguished from stochastic damages without a
      definable threshold dose. The occurrence of deterministic damages depends on the
      dose and the developmental stage of the unborn at the time of radiation. To
      calculate the risks of an in-utero radiation exposure a three-stage concept is
      commonly applied. Depending on the amount of radiation, the radiation dose is
      either estimated, roughly calculated using standard tables or, in critical cases,
      accurately calculated based on the individual event. The complexity of the
      calculation thereby increases from stage to stage. An estimation based on stage
      one is easily feasible whereas calculations based on stages two and especially
      three are more complex and often necessitate execution by specialists. This
      article demonstrates in detail the risks for the unborn child pertaining to its
      developmental phase and explains the three-stage concept as an evaluation scheme.
      It should be noted, that all risk estimations are subject to considerable
      uncertainties. * Radiation exposure of the unborn child can result in both
      deterministic as well as stochastic damage und hitherto should be avoided or
      reduced to a minimum.* In case of radiation a suitable hygiene consultation may
      be necessary.* For risk assessment a three-stage concept is applied, which,
      depending on the radiation exposure, estimates or calculates the dose for the
      unborn child.* The radiologist plays a crucial role as a competent advisor and
      provider of reliable expert information. Citation Format: * Scharwachter C, Roser
      A, Schwartz CA et al. Prenatal Radiation Exposure: Dose Calculation. Fortschr
      Rontgenstr 2015; 187: 338 - 346. 

PMID- 25750113
TI  - Modern Radiological Postoperative Diagnostics of the Hip Joint in Children and
      Adults.
AB  - The assessment of bone healing and loosening of endoprosthesis material was long
      the primary indication for postoperative projection radiography and CT imaging of
      the hip joint following trauma and endoprosthesis implantation. With the
      increasing number of joint-preserving surgery, e. g. of surgical hip luxation and
      hip arthroscopy for the treatment of femoroacetabular impingement (FAI), high
      resolution imaging of intra-articular pathologies before and after surgery has
      become increasingly important. In this review article, diagnostic imaging of the
      hip joint is presented following common trauma surgery and orthopedic surgery
      interventions. The imaging modalities of projection radiography, CT and MRI
      including direct MR-arthrography are discussed with regard to their diagnostic
      capability in the postoperative assessment of the hip joint. Among others topics,
      imaging is discussed following hip arthroplasty, following surgical hip luxation
      and arthroscopic interventions for the treatment of FAI, as well as following
      core decompression for avascular necrosis of the femoral head. Moreover,
      orthopedic interventions of the hip joint in children and adolescents are
      presented and the dedicated reporting of postoperative imaging is outlined. KEY
      POINTS: * Consolidation of osteotomies and position of implants should be
      assessed in postoperative imaging. * MRI is useful for confirming correct
      articulation after treatment of congenital hip dislocation. * Radiologically
      assessable complications after total hip replacement are inlay wear, loosening,
      dislocation, periarticular ossifications and infection. * MRI can detect and
      classify pseudotumours in cases of metal-metal pairing after total hip
      replacement.

PMID- 25750114
TI  - [Increased sclerosis of the iliac fossa: not at first glance a chondroblastic
      osteosarcoma of the pelvis].

PMID- 25750115
TI  - Stiff Young Woman.

PMID- 25750116
TI  - [Rare manifestation of atherosclerosis in the abdominal aorta in the form of a
      "Coral Reef aorta"].

PMID- 25750117
TI  - [Cerebral infarction in the posterior circulation region with active giant cell
      arteritis - rapid and definitive diagnosis by CTA].

PMID- 25750118
TI  - [Amyloidosis of the brain].

PMID- 25750119
TI  - [Primary cardiac tumor - differential angiosarcoma diagnosis versus
      extraintestinal GIST].

PMID- 25750120
TI  - [Diffuse increased FDG uptake of the atrial myocardium in the PET-CT as a result
      of irradiation-induced afterload].

PMID- 25750121
TI  - [Acute, subperiosteal hematoma of the ilium].

PMID- 25750122
TI  - [A rare cause of pathological fractures in childhood: primary hyperoxaluria].

PMID- 25750123
TI  - [Ileal varices as a rare cause of lower gastrointestinal bleeding].

PMID- 25750124
TI  - The role of molecular imaging in the evaluation of myocardial and peripheral
      angiogenesis.
AB  - Angiogenesis, or the formation of new microvasculature, is a physiological
      process that may occur in the setting of chronic tissue ischemia and can play an
      important role in improving tissue perfusion and blood flow following myocardial
      infarction or in the presence of peripheral vascular disease (PVD). Molecular
      imaging of angiogenesis within the cardiovascular system is a developing field of
      study. Targeted imaging of angiogenesis has the potential for non-invasive
      assessment of the underlying molecular signaling events associated with the
      angiogenic process and, when applied in conjunction with physiological perfusion
      imaging, may be utilized to predict and evaluate clinical outcomes in the setting
      of ischemic heart disease or PVD. This review discusses the developing
      radiotracer-based imaging techniques and technology currently in use that possess
      potential for clinical translation, with specific focus on PET and SPECT imaging
      of myocardial and peripheral angiogenesis. 

PMID- 25750125
TI  - The guanine nucleotide exchange factor (GEF) Asef2 promotes dendritic spine
      formation via Rac activation and spinophilin-dependent targeting.
AB  - Dendritic spines are actin-rich protrusions that establish excitatory synaptic
      contacts with surrounding neurons. Reorganization of the actin cytoskeleton is
      critical for the development and plasticity of dendritic spines, which is the
      basis for learning and memory. Rho family GTPases are emerging as important
      modulators of spines and synapses, predominantly through their ability to
      regulate actin dynamics. Much less is known, however, about the function of
      guanine nucleotide exchange factors (GEFs), which activate these GTPases, in
      spine and synapse development. In this study we show that the Rho family GEF
      Asef2 is found at synaptic sites, where it promotes dendritic spine and synapse
      formation. Knockdown of endogenous Asef2 with shRNAs impairs spine and synapse
      formation, whereas exogenous expression of Asef2 causes an increase in spine and
      synapse density. This effect of Asef2 on spines and synapses is abrogated by
      expression of GEF activity-deficient Asef2 mutants or by knockdown of Rac,
      suggesting that Asef2-Rac signaling mediates spine development. Because Asef2
      interacts with the F-actin-binding protein spinophilin, which localizes to
      spines, we investigated the role of spinophilin in Asef2-promoted spine
      formation. Spinophilin recruits Asef2 to spines, and knockdown of spinophilin
      hinders spine and synapse formation in Asef2-expressing neurons. Furthermore,
      inhibition of N-methyl-d-aspartate receptor (NMDA) activity blocks spinophilin
      mediated localization of Asef2 to spines. These results collectively point to
      spinophilin-Asef2-Rac signaling as a novel mechanism for the development of
      dendritic spines and synapses. 

PMID- 25750126
TI  - Systemic amyloidosis: lessons from beta2-microglobulin.
AB  - beta2-Microglobulin is responsible for systemic amyloidosis affecting patients
      undergoing long-term hemodialysis. Its genetic variant D76N causes a very rare
      form of familial systemic amyloidosis. These two types of amyloidoses differ
      significantly in terms of the tissue localization of deposits and for major
      pathological features. Considering how the amyloidogenesis of the beta2
      microglobulin mechanism has been scrutinized in depth for the last three decades,
      the comparative analysis of molecular and pathological properties of wild type
      beta2-microglobulin and of the D76N variant offers a unique opportunity to
      critically reconsider the current understanding of the relation between the
      protein's structural properties and its pathologic behavior. 

PMID- 25750127
TI  - Rapid Trimming of Cell Surface Polysialic Acid (PolySia) by Exovesicular
      Sialidase Triggers Release of Preexisting Surface Neurotrophin.
AB  - As acidic glycocalyx on primary mouse microglial cells and a mouse microglial
      cell line Ra2, expression of polysialic acid (polySia/PSA), a polymer of the
      sialic acid Neu5Ac (N-acetylneuraminic acid), was demonstrated. PolySia is known
      to modulate cell adhesion, migration, and localization of neurotrophins mainly on
      neural cells. PolySia on Ra2 cells disappeared very rapidly after an inflammatory
      stimulus. Results of knockdown and inhibitor studies indicated that rapid surface
      clearance of polySia was achieved by secretion of endogenous sialidase Neu1 as an
      exovesicular component. Neu1-mediated polySia turnover was accompanied by the
      release of brain-derived neurotrophic factor normally retained by polySia
      molecules. Introduction of a single oxygen atom change into polySia by exogenous
      feeding of the non-neural sialic acid Neu5Gc (N-glycolylneuraminic acid) caused
      resistance to Neu1-induced polySia turnover and also inhibited the associated
      release of brain-derived neurotrophic factor. These results indicate the
      importance of rapid turnover of the polySia glycocalyx by exovesicular sialidases
      in neurotrophin regulation. 

PMID- 25750128
TI  - Examination of Sec22 Homodimer Formation and Role in SNARE-dependent Membrane
      Fusion.
AB  - Soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE)
      protein complexes play essential roles in catalyzing intracellular membrane
      fusion events although the assembly pathway and molecular arrangement of SNARE
      complexes in membrane fusion reactions are not well understood. Here we monitored
      interactions of the R-SNARE protein Sec22 through a cysteine scanning approach
      and detected efficient formation of cross-linked Sec22 homodimers in cellular
      membranes when cysteine residues were positioned in the SNARE motif or C terminus
      of the transmembrane domain. When specific Sec22 cysteine derivatives are present
      on both donor COPII vesicles and acceptor Golgi membranes, the formation of
      disulfide cross-links provide clear readouts on trans- and cis-SNARE arrangements
      during this fusion event. The Sec22 transmembrane domain was required for
      efficient homodimer formation and for membrane fusion suggesting a functional
      role for Sec22 homodimers. We propose that Sec22 homodimers promote assembly of
      higher-order SNARE complexes to catalyze membrane fusion. Sec22 is also reported
      to function in macroautophagy and in formation of endoplasmic reticulum-plasma
      membrane contact sites therefore homodimer assembly may regulate Sec22 activity
      across a range of cellular processes. 

PMID- 25750130
TI  - A review of forty five open tibial fractures covered with free flaps. Analysis of
      complications, microbiology and prognostic factors.
AB  - PURPOSE: Treatment of open fractures is complex and controversial. The purpose of
      the present study is to add evidence to the management of open tibial fractures,
      where tissue loss necessitates cover with a free flap. We identified factors that
      increase the risk of complications. We questioned whether early flap coverage
      improved the clinical outcome and whether we could improve our antibiotic
      treatment of open fractures. METHODS: From 2002 to 2013 we treated 56 patients
      with an open tibial fracture covered with a free flap. We reviewed patient
      records and databases for type of trauma, smoking, time to tissue cover,
      infection, amputations, flap loss and union of fracture. We identified factors
      that increase the risk of complications. We analysed the organisms cultured from
      open fractures to propose the optimal antibiotic prophylaxis. Follow-up was a
      minimum of one year. Primary outcome was infection, bacterial sensitivity
      pattern, amputation, flap failure and union of the fracture. RESULTS: When soft
      tissue cover was delayed beyond seven days, infection rate increased from 27 to
      60 % (p < 0.04). High-energy trauma patients had a higher risk of amputation,
      infection, flap failure and non-union. Smokers had a higher risk of non-union and
      flap failure. The bacteria found were often resistant to Cefuroxime,
      aminoglycosides or amoxicillin, but sensitive to vancomycin or meropenem.
      CONCLUSION: Flap cover within one week is essential to avoid infection. High
      energy trauma and smoking are important predictors of complications. We suggest
      antibiotic prophylaxis with vancomycin and meropenem until the wound is covered
      in these complex injuries.

PMID- 25750129
TI  - Down-regulation of ZmEXPB6 (Zea mays beta-expansin 6) protein is correlated with
      salt-mediated growth reduction in the leaves of Z. mays L.
AB  - The salt-sensitive crop Zea mays L. shows a rapid leaf growth reduction upon NaCl
      stress. There is increasing evidence that salinity impairs the ability of the
      cell walls to expand, ultimately inhibiting growth. Wall-loosening is a
      prerequisite for cell wall expansion, a process that is under the control of cell
      wall-located expansin proteins. In this study the abundance of those proteins was
      analyzed against salt stress using gel-based two-dimensional proteomics and two
      dimensional Western blotting. Results show that ZmEXPB6 (Z. mays beta-expansin 6)
      protein is lacking in growth-inhibited leaves of salt-stressed maize. Of note,
      the exogenous application of heterologously expressed and metal-chelate-affinity
      chromatography-purified ZmEXPB6 on growth-reduced leaves that lack native ZmEXPB6
      under NaCl stress partially restored leaf growth. In vitro assays on frozen
      thawed leaf sections revealed that recombinant ZmEXPB6 acts on the capacity of
      the walls to extend. Our results identify expansins as a factor that partially
      restores leaf growth of maize in saline environments. 

PMID- 25750131
TI  - Comparison of the pre-shaped anatomical locking plate of 3.5 mm versus 4.5 mm for
      the treatment of tibial plateau fractures.
AB  - PURPOSE: Treatment of tibial plateau fractures is discussed. A retrospective
      comparative study of fractures treated with an anatomical locking plate of 4.5 mm
      or 3.5 mm. Our hypothesis is that the 3.5 mm plates give an equivalent hold of
      fractures with comparable results and better clinical tolerance. METHODS: From
      May 2010 to October 2011, 18 patients were operated on using a 4.5-mm LCPTM
      anatomical plate (group A) and 20 patients received a3.5-mm LCPTM anatomical
      plate (group B). Groups were comparable. One fracture was open. RESULTS: For the
      Group A, 14 patients had a follow up of 35.3 months and for the Group B, 16
      patients had a follow up of 27 months. Mobility was comparable in both groups.
      The Hospital for Special Surgery (HSS) score was 86.4 versus 80.6, the Lysholm
      score was 83.6 versus 77 for groups A and B respectively. Consolidation was 3.25
      months versus 3.35 months and mean axis was 183.1 degrees  versus 181.6 degrees 
      for groups A and B. Mechanical axes during revision were statistically different
      to the controlateral axes. One secondary displacement was noted in group A and
      one secondary displacement in group B. Group A had eight patients reporting
      discomfort with the material versus three in group B (p < 0.05). CONCLUSION: The
      hypothesis is proven. In regards to the results, there is no significant
      difference between the two groups but the clinical tolerance was better in group
      B. More time is needed in the long term to better evaluate these severe
      fractures.

PMID- 25750132
TI  - Bone transplantation and tissue engineering, part IV. Mesenchymal stem cells:
      history in orthopedic surgery from Cohnheim and Goujon to the Nobel Prize of
      Yamanaka.
AB  - In 1867 the German pathologist Cohnheim hypothesized that non-hematopoietic, bone
      marrow-derived cells could migrate through the blood stream to distant sites of
      injury and participate in tissue regeneration. In 1868, the French physiologist
      Goujon studied the osteogenic potential of bone marrow on rabbits. Friedenstein
      demonstrated the existence of a nonhematopoietic stem cell within bone marrow
      more than a hundred years later. Since this discovery, the research on
      mesenchymal stem cell (MSC) has explored their therapeutic potential. The
      prevalent view during the second century was that mature cells were permanently
      locked into the differentiated state and could not return to a fully immature,
      pluripotent stem-cell state. Recently, Japanese scientist (first orthopaedist)
      Shinya Yamanaka proved that introduction of a small set of transcription factors
      into a differentiated cell was sufficient to revert the cell to a pluripotent
      state. Yamanaka shared the Nobel Prize in Physiology or Medicine and opened a new
      door for potential applications of MSCs. This manuscript describes the concept of
      MSCs from the period when it was relegated to the imagination to the beginning of
      the twenty-first century and their application in orthopaedic surgery.

PMID- 25750134
TI  - "Open-book" pelvic fracture with soft tissue serious damage in a child.
AB  - Open-book fractures of the pelvis are uncommon during childhood and require
      urgent treatment from the association with other abdominal, vascular or nervous
      injuries. The case discussed is an open-book fracture (type B1, Tile
      classification) associated with triradiate cartilage injury (type I, Salter
      Harris classification) in an 11-year-old female. Surgical treatment was delayed
      for 2 months due to an associated extensive cutaneous lesion which required an
      adequate treatment. The delayed intervention did not affect the radiological and
      clinical healing of the fracture. 

PMID- 25750133
TI  - Sex, but not Apolipoprotein E Polymorphism, Differences in Spatial Performance in
      Young Adults.
AB  - The purpose of this study was to examine how sex and apolipoprotein E (APOE)
      genotype contribute to individual differences in spatial learning and memory. The
      associations of APOE genotype with neurocognitive function have been well studied
      among the elderly but less is known at earlier ages. Young adults (n = 169, 88
      females) completed three neurocognitive tasks: mental rotation, spatial span, and
      Memory Island, a spatial navigation test. Males outperformed females on all three
      tasks: finding the hidden targets more quickly on Memory Island (Cohen's d =
      0.62) and obtaining higher scores on mental rotation (d = 0.54) and spatial span
      (d = 0.37). In contrast, no significant effects of APOE were observed. The
      identified sex differences elaborate upon past literature documenting sexually
      dimorphic performance on specific neurobehavioral tasks.

PMID- 25750135
TI  - Misidentification of English Language Proficiency in Triage: Impact on
      Satisfaction and Door-to-Room Time.
AB  - We examined triage nurses' assessment of patients' language proficiency compared
      to patients' self-reported proficiency and the impact of language discordance on
      door-to-room time and patient satisfaction. This was a prospective study of
      emergency department walk-in patients. Patients completed a survey in which they
      identified their language proficiency. On a Likert scale, patients ranked how
      well they felt they were understood and how satisfied they were with the triage
      process. Nurses completed surveys identifying the patient's primary language and
      how well they felt they understood the patient. Door-to-room times were obtained
      from medical records. 163 patients were enrolled. 66% of patients identified
      themselves as having good English proficiency, while 34% of patients had limited
      English proficiency. Nurses misclassified 27% of self-identified Spanish-speaking
      patients as being English proficient. Spanish-speakers felt less satisfied with
      triage than English-speakers (p < 0.01). There were no differences in door-to
      room time. Triage nurses overestimate patient language skills. Spanish-speaking
      patients feel less satisfied with triage than English-speakers.

PMID- 25750137
TI  - No need for use of drainage after minimally invasive unicompartmental knee
      arthroplasty: a prospective randomized, controlled trial.
AB  - OBJECTIVE: Drainage is a common procedure in unicompartmental knee arthroplasty
      (UKA), but evidence regarding its effectiveness is lacking. The aim of this study
      was to investigate the benefits of drainage after minimally invasive UKA with
      effective blood loss management. METHODS: This was a prospective, randomized,
      controlled trial to determine whether drainage after UKA provides benefits with
      respect to blood loss, drainage volume, complications, pain score, knee score,
      range of motion and cost. The 96 patients who underwent surgery between January
      2012 and March 2013 were randomly divided into two groups: group A (n = 48) was
      treated without drainage, and group B (n = 48) with drainage. All UKA procedures
      were performed with the same minimally invasive surgical technique. Tranexamic
      acid and bone wax were used for the management of blood loss in all patients. The
      preoperative baseline parameters of the two groups did not differ significantly.
      RESULTS: The mean drainage volume in group B was 75.7 +/- 51.2 mL when the
      drainage was present. Total blood loss in group A and group B was 240.3 +/- 73.3
      mL and 274.1 +/- 99.5 mL, respectively. These amounts did not differ
      significantly but both were significantly lower than the data reported for total
      knee arthroplasty. There was no difference in mean postoperative hemoglobin and
      hematocrit between groups. Differences in wound infection, incidence of deep vein
      thrombosis, postoperative Hospital for Special Surgery knee score, visual analog
      score, and range of motion were not statistically significant between groups.
      Hospitalization costs for UKA were lower in the absence of drainage. CONCLUSIONS:
      The use of drainage in unilateral UKA provides no apparent advantage. With
      effective blood loss management and a minimally invasive procedure, blood loss
      and drainage volume in UKA are very low. Drainage does not improve the results.
      Foregoing non-drainage after UKA reduces both hospital costs and visible blood
      loss. Therefore, drainage is unnecessary in routine UKA.

PMID- 25750136
TI  - Physical Activity Disparities Between US-born and Immigrant Children by Maternal
      Region of Origin.
AB  - We examined and compared patterns in physical activity participation for children
      of US-born and immigrant mothers from seven world geographic regions, and tested
      whether the physical activity differences were attenuated by socioeconomic status
      or maternal language proficiency. Using the Early Childhood Longitudinal Study
      Kindergarten data (N = 18,850) we utilized logistic regression to predict
      adequate vigorous physical activity and participation in group and individual
      sports for kindergarten children. US-born children of US-born parents have
      significantly higher rates of physical activity compared to immigrant children.
      Children of Mexican, Southeast Asian, and Caribbean immigrants were especially
      unlikely to participate in sports. These disparities were not significantly
      attenuated by socioeconomic status, but accounting for language proficiency
      reduced some differences between the US-born and immigrant children, particularly
      for group sports participation. Researchers interested in improving the physical
      activity patterns of second-generation children should consider the relevance of
      language barriers in promoting healthy living. 

PMID- 25750139
TI  - There ain't nothing like a Dame: a commentary on Lonsdale (1947) 'Divergent beam
      X-ray photography of crystals'.
AB  - Prof. Dame Kathleen Lonsdale was one of the two first female Fellows of the Royal
      Society, having originally been a student of that great British scientist and
      Nobel Laureate William Henry Bragg. She came to fame initially for her solution
      of the crystal structure of hexamethyl benzene, thus demonstrating that the
      benzene ring was flat, of considerable importance to organic chemistry, where it
      had been proposed before but without proof. This was at a time when the solution
      of crystal structures was in its infancy, and in its day this work was considered
      a triumph. As a rare example then of a female physicist, Lonsdale became
      interested in various aspects of the diffraction of X-rays, and in particular
      published an important paper on a form of diffraction in which a strongly
      divergent source was used rather than the usual highly collimated beam. The
      photographs thus obtained showed a series of arcs and circles, whose positions
      were so sensitive that they could be used to determine the quality of crystals
      such as diamond, and even to calculate their lattice dimensions, and hence carbon
      carbon bond lengths, to hitherto extraordinary precision. Lonsdale also became
      known not just as a scientist but as a peace activist and an active member of the
      Society of Friends. This commentary was written to celebrate the 350th
      anniversary of the journal Philosophical Transactions of the Royal Society. 

PMID- 25750138
TI  - Role of second-look ultrasound examinations for MR-detected lesions in patients
      with breast cancer.
AB  - PURPOSE: To assess the clinical value of second-look ultrasound (US) examination
      for the evaluation of additional enhancing lesions detected on magnetic resonance
      (MR) imaging. MATERIALS AND METHODS: Between May 2008 and February 2011, 794
      consecutive patients with histologically confirmed breast cancer underwent breast
      MR imaging. We included 101 patients with 132 additional enhancing breast lesions
      detected on MR imaging who underwent second-look US.  The imaging features and
      lesion category according to the Breast Imaging and Reporting and Data System (BI
      RADS) were assessed with MR and US imaging, respectively. RESULTS: According to
      the BI-RADS system, 67 lesions (50.8 %) were classified as category 0, 33 lesions
      (25.0 %) as category 3, and 32 lesions (24.2 %) as category 4. Of the 67
      indeterminate lesions on MR imaging, 34 (50.7 %) were demonstrated on second-look
      US. 11 of these 34 lesions showed suspicious sonographic features, including 1
      lesion that showed malignancy (9.1 %, 1/11). Most of the suspicious lesions on MR
      imaging (26 of 32 BI-RADS category 4 lesions, 81.3 %) were demonstrated on second
      look US, and 17 were malignant (65.4 %, 17/26). Of the 6 BI-RADS category 4
      lesions without sonographic correlation, 1 was malignant (16.7 %, 1/6).
      CONCLUSION: Second-look US examination was useful for evaluating MR-detected
      lesions in patients with breast cancer.

PMID- 25750140
TI  - Learned modesty and the first lady's comet: a commentary on Caroline Herschel
      (1787) 'An account of a new comet'.
AB  - Long before women were allowed to become Fellows of the Royal Society, or obtain
      university degrees, one woman managed to get her voice heard, her discovery
      verified and her achievement celebrated. That woman was Caroline Herschel, who,
      as this paper will discuss, managed to find ways to fit comet discoveries into
      her domestic life, and present them in ways that were socially acceptable.
      Caroline lived in a time when strict rules dictated how women (and men) should
      behave and present themselves and their work. Caroline understood these rules,
      and used them carefully as she announced each discovery, starting with this comet
      which she found in 1786. Caroline discovered her comets at a time when
      astronomers were mainly concerned with position, identifying where things were
      and how they were moving. Since her discoveries, research has moved on, as
      astronomers, using techniques from other fields, and most recently sending
      experiments into space, have learned more about what comets are and what they can
      tell us about our solar system. Caroline's paper marks one small, early step in
      this much bigger journey to understand comets. This commentary was written to
      celebrate the 350th anniversary of the journal Philosophical Transactions of the
      Royal Society. 

PMID- 25750141
TI  - How does your crystal grow? A commentary on Burton, Cabrera and Frank (1951) 'The
      growth of crystals and the equilibrium structure of their surfaces'.
AB  - The key ideas presented in the classic paper 'The growth of crystals and the
      equilibrium structure of their surfaces' by W. K. Burton, N. Cabrera and F. C.
      Frank, published in Philosophical Transactions A in 1951, are summarized and put
      in the context of both the state of knowledge at the time of publication and the
      considerable amount of work since that time that has built on and developed these
      ideas. Many of these developments exploit the huge increase in the capabilities
      of computer modelling that complement the original analytic approach of the
      paper. The dearth of relevant experimental data at the time of the original
      publication has been transformed by the application of increasingly sophisticated
      modern methods of surface science. This commentary was written to celebrate the
      350th anniversary of the journal Philosophical Transactions of the Royal Society.

PMID- 25750142
TI  - A harbinger of plate tectonics: a commentary on Bullard, Everett and Smith (1965)
      'The fit of the continents around the Atlantic'.
AB  - In the 1960s, geology was transformed by the paradigm of plate tectonics. The
      1965 paper of Bullard, Everett and Smith was a linking transition between the
      theories of continental drift and plate tectonics. They showed, conclusively,
      that the continents around the Atlantic were once contiguous and that the
      Atlantic Ocean had grown at rates of a few centimetres per year since the Early
      Jurassic, about 160 Ma. They achieved fits of the continental margins at the 500
      fathom line (approx. 900 m), not the shorelines, by minimizing misfits between
      conjugate margins and finding axes, poles and angles of rotation, using Euler's
      theorem, that defined the unique single finite difference rotation that carried
      congruent continents from contiguity to their present positions, recognizing that
      the real motion may have been more complex around a number of finite motion
      poles. Critically, they were concerned only with kinematic reality and were not
      restricted by considerations of the mechanism by which continents split and
      oceans grow. Many of the defining features of plate tectonics were explicit or
      implicit in their reconstructions, such as the torsional rigidity of continents,
      Euler's theorem, closure of the Tethyan ocean(s), major continental margin shear
      zones, the rapid rotation of small continental blocks (Iberia) around nearby
      poles, the consequent opening of small wedge-shaped oceans (Bay of Biscay), and
      misfit overlaps (deltas and volcanic piles) and underlaps (stretched continental
      edges). This commentary was written to celebrate the 350th anniversary of the
      journal Philosophical Transactions of the Royal Society. 

PMID- 25750143
TI  - Newton shows the light: a commentary on Newton (1672) 'A letter ... containing
      his new theory about light and colours...'.
AB  - Isaac Newton's reputation was initially established by his 1672 paper on the
      refraction of light through a prism; this is now seen as a ground-breaking
      account and the foundation of modern optics. In it, he claimed to refute
      Cartesian ideas of light modification by definitively demonstrating that the
      refrangibility of a ray is linked to its colour, hence arguing that colour is an
      intrinsic property of light and does not arise from passing through a medium.
      Newton's later significance as a world-famous scientific genius and the apparent
      confirmation of his experimental results have tended to obscure the realities of
      his reception at the time. This paper explores the rhetorical strategies Newton
      deployed to convince his audience that his conclusions were certain and
      unchallengeable. This commentary was written to celebrate the 350th anniversary
      of the journal Philosophical Transactions of the Royal Society. 

PMID- 25750144
TI  - Sir Humphry Davy and the coal miners of the world: a commentary on Davy (1816)
      'An account of an invention for giving light in explosive mixtures of fire-damp
      in coal mines'.
AB  - In the period between 1815 and 1818, Sir Humphry Davy read four papers to the
      Royal Society and published a monograph dealing with a safety lamp for coal
      miners, all of which record in detail the experimental work that he carried out,
      with his assistant Michael Faraday, so as to determine how to prevent
      catastrophic accidents in coal mines by the explosion of fire-damp (methane) in
      the presence of a naked flame. This article describes the key experiments that he
      performed at the Royal Institution and some of the subsequent trials made in the
      coal mines of the north of England. It begins, however, with an account of Davy's
      prior achievements in science before he was approached for help by the clergymen
      and doctors in the Gateshead and Newcastle upon Tyne areas. There is little doubt
      that the Davy lamp, from the 1820s onwards, transformed the coal industry
      worldwide. It also profoundly influenced the science of combustion, and in the
      words of a pioneer in that field, W. A. Bone, FRS, 'There is no better model of
      logical experimental procedure, accurate reasoning, philosophical outlook and
      fine literary expression.' It is a remarkable fact that it took Davy essentially
      only two weeks from the time he was given samples of fire-damp to solve the
      problem and to devise his renowned miner's safety lamp. A brief account is also
      given of the contemporaneous invention of a safety lamp by George Stephenson, and
      of some of Davy's subsequent accomplishments. This commentary was written to
      celebrate the 350th anniversary of the journal Philosophical Transactions of the
      Royal Society. 

PMID- 25750145
TI  - The birth of the electric machines: a commentary on Faraday (1832) 'Experimental
      researches in electricity'.
AB  - The history of science is filled with examples of key discoveries and
      breakthroughs that have been published as landmark texts or journal papers, and
      to which one can trace the origins of whole disciplines. Such paradigm-shifting
      publications include Copernicus' De revolutionibus orbium coelestium (1543),
      Isaac Newton's Philosophiae Naturalis Principia Mathematica (1687) and Albert
      Einstein's papers on relativity (1905 and 1915). Michael Faraday's 1832 paper on
      electromagnetic induction sits proudly among these works and in a sense can be
      regarded as having an almost immediate effect in transforming our world in a very
      real sense more than any of the others listed. Here we review the status of the
      subject-the relationship between magnetism and electricity both before and after
      Faraday's paper and delve into the details of the key experiments he carried out
      at the Royal Institution outlining clearly how he discovered the process of
      electromagnetic induction, whereby an electric current could be induced to flow
      through a conductor that experiences a changing magnetic field. His ideas would
      not only enable Maxwell's later development of his theory of classical
      electromagnetism, but would directly lead to the development of the electric
      dynamo and electric motor, two technological advances that are the very
      foundations of the modern world. This commentary was written to celebrate the
      350th anniversary of the journal Philosophical Transactions of the Royal Society.

PMID- 25750146
TI  - Gases, God and the balance of nature: a commentary on Priestley (1772)
      'Observations on different kinds of air'.
AB  - Historians of chemistry usually associate the eighteenth century with the
      Chemical Revolution, but it could just as readily be called 'the century of
      gases' (or 'airs', as they were called in the eighteenth century). In the early
      part of the century, the British pneumatic chemists struggled to replace the
      traditional notion 'Air', understood as an inert chemical element, with the
      concept of 'air', regarded as the third state of matter, encompassing a wide
      variety of chemical species. These developments constituted a necessary condition
      for the Chemical Revolution, which occurred in the latter part of the century. In
      'Observations', Priestley took pneumatic chemistry to a new level, with the
      discovery of eight simple inorganic gases. Motivated by his belief in a
      benevolent God and a pious utilitarianism, Priestly explored the role of the
      atmosphere in the balance of nature and the politics of the state, which he
      linked to the movement of Rational Dissent. He styled himself an 'aerial
      philosopher' to signal the interdisciplinary nature of his inquiries, which he
      regarded not as a branch of ordinary chemistry, but as a mode of thought that
      encompassed physics, chemistry and natural theology. Priestley saw it as a source
      of principles and secrets of nature more extensive than that of 'gravity itself'.
      This commentary was written to celebrate the 350th anniversary of the journal
      Philosophical Transactions of the Royal Society. 

PMID- 25750147
TI  - Tactics for mechanized reasoning: a commentary on Milner (1984) 'The use of
      machines to assist in rigorous proof'.
AB  - Robin Milner's paper, 'The use of machines to assist in rigorous proof',
      introduces methods for automating mathematical reasoning that are a milestone in
      the development of computer-assisted theorem proving. His ideas, particularly his
      theory of tactics, revolutionized the architecture of proof assistants. His
      methodology for automating rigorous proof soundly, particularly his theory of
      type polymorphism in programing, led to major contributions to the theory and
      design of programing languages. His citation for the 1991 ACM A.M. Turing award,
      the most prestigious award in computer science, credits him with, among other
      achievements, 'probably the first theoretically based yet practical tool for
      machine assisted proof construction'. This commentary was written to celebrate
      the 350th anniversary of the journal Philosophical Transactions of the Royal
      Society. 

PMID- 25750148
TI  - First steps in modelling turbulence and its origins: a commentary on Reynolds
      (1895) 'On the dynamical theory of incompressible viscous fluids and the
      determination of the criterion'.
AB  - Reynolds' paper sought to explain the change in character of flow through a pipe
      from laminar to turbulent that his earlier experiments had shown to occur when
      the dimensionless group that today bears his name exceeded approximately 2000.
      This he did by decomposing the velocity into mean and fluctuating components and
      noting how the average kinetic energy generation and dissipation rates changed
      with Reynolds number. The paper was only grudgingly accepted by two very
      distinguished referees and initially raised little external interest. As years
      went by, however, the averaged form of the equations of motion, known as the
      Reynolds equations (which were an intermediate stage in Reynolds' analysis)
      became the acknowledged starting point for computing turbulent flows. Moreover,
      some 50 years after his paper, a refinement of his strategy for predicting
      transition was also successfully taken up. For some engineering problems, the
      continual rapid growth of computing resources has meant that more detailed
      approaches for computing turbulent flow phenomena can nowadays be employed.
      However, this growth of computing power likewise makes possible a Reynolds
      averaging strategy for complex flow systems in industry or the environment which
      formerly had to adopt less comprehensive analyses. Thus, Reynolds' approach may
      well remain in use throughout the present century. This commentary was written to
      celebrate the 350th anniversary of the journal Philosophical Transactions of the
      Royal Society. 

PMID- 25750149
TI  - Bending space-time: a commentary on Dyson, Eddington and Davidson (1920) 'A
      determination of the deflection of light by the Sun's gravitational field'.
AB  - The famous eclipse expedition of 1919 to Sobral, Brazil, and the island of
      Principe, in the Gulf of Guinea, led by Dyson, Eddington and Davidson was a
      turning point in the history of relativity, not only because of its importance as
      a test of Einstein's General Theory of Relativity, but also because of the
      intense public interest which was aroused by the success of the expedition. The
      dramatic sequence of events which occurred is reviewed, as well as the long-term
      impact of its success. The gravitational bending of electromagnetic waves by
      massive bodies is a subject of the greatest importance for contemporary and
      future astronomy, astrophysics and cosmology. Examples of the potential impact of
      this key tool of modern observational astronomy are presented. This commentary
      was written to celebrate the 350th anniversary of the journal Philosophical
      Transactions of the Royal Society. 

PMID- 25750150
TI  - Deep questions about the nature of early-life signals: a commentary on Lister
      (1673) 'A description of certain stones figured like plants'.
AB  - In 1673, Martin Lister explored the preservation of 'St Cuthbert's beads' plus
      other fossil crinoid remains from approximately 350 Ma Carboniferous limestone in
      northern England. He used taphonomic evidence (transport, disarticulation, burial
      and cementation) to infer an origin as petrified plant remains, in contrast with
      his views expressed elsewhere that fossil mollusc shells could have formed
      abiogenically, by 'plastic forces' within rock. Lister also observed pentagonal
      symmetry, now seen as characteristic of living echinoderm skeletons. A postscript
      from John Ray supports Lister's 'taphonomic' observations and accepts the
      biogenicity of these fossil 'vegetables'. Ray then concluded with a prophecy,
      predicting the discovery of comparable living fossils in remote ocean waters.
      These early discussions compare with current debates about the character of
      candidate microfossils from the early Earth and Mars. Interesting biomorphs are
      now tested against the abiogenic null hypotheses, making use of features such as
      those pioneered by Lister, including evidence for geological context, rules for
      growth and taphonomy. Advanced techniques now allow us to extend this list of
      criteria to include the nanoscale mapping of biology-like behaviour patterns plus
      metabolic pathways. Whereas the science of palaeobiology once began with tests
      for biogenicity, the same is now true for geobiology and astrobiology. This
      commentary was written to celebrate the 350th anniversary of the journal
      Philosophical Transactions of the Royal Society. 

PMID- 25750151
TI  - From evidence to understanding: a commentary on Fisher (1922) 'On the
      mathematical foundations of theoretical statistics'.
AB  - The nature of statistics has changed over time. It was originally concerned with
      descriptive 'matters of state'--with summarizing population numbers, economic
      strength and social conditions. But during the course of the twentieth century
      its aim broadened to include inference--how to use data to shed light on
      underlying mechanisms, about what might happen in the future, about what would
      happen if certain actions were taken. Central to this development was Ronald
      Fisher. Over the course of his life he was responsible for many of the major
      conceptual advances in statistics. This is particularly illustrated by his 1922
      paper, in which he introduced many of the concepts which remain fundamental to
      our understanding of how to extract meaning from data, right to the present day.
      It is no exaggeration to say that Fisher's work, as illustrated by the ideas he
      described and developed in this paper, underlies all modern science, and much
      more besides. This commentary was written to celebrate the 350th anniversary of
      the journal Philosophical Transactions of the Royal Society.

PMID- 25750152
TI  - Heat, work and subtle fluids: a commentary on Joule (1850) 'On the mechanical
      equivalent of heat'.
AB  - James Joule played the major role in establishing the conservation of energy, or
      the first law of thermodynamics, as a universal, all-pervasive principle of
      physics. He was an experimentalist par excellence and his place in the
      development of thermodynamics is unarguable. This article discusses Joule's life
      and scientific work culminating in the 1850 paper, where he presented his
      detailed measurements of the mechanical equivalent of heat using his famous
      paddle-wheel apparatus. Joule's long series of experiments in the 1840s leading
      to his realisation that the conservation of energy was probably of universal
      validity is discussed in context with the work of other pioneers, notably Sadi
      Carnot, who effectively formulated the principle of the second law of
      thermodynamics a quarter of a century before the first law was accepted. The
      story of Joule's work is a story of an uphill struggle against a critical
      scientific establishment unwilling to accept the mounting evidence until it was
      impossible to ignore. His difficulties in attracting funding and publishing in
      reputable journals despite the quality of his work will resonate with many young
      scientists and engineers of the present day. This commentary was written to
      celebrate the 350th anniversary of the journal Philosophical Transactions of the
      Royal Society. 

PMID- 25750153
TI  - An amateur's contribution to the design of Telford's Menai Suspension Bridge: a
      commentary on Gilbert (1826) 'On the mathematical theory of suspension bridges'.
AB  - Davies Gilbert's work on the catenary is notable on two counts. First, it
      influenced Thomas Telford in formulating his final design for the Menai Strait
      suspension bridge (1826); and second, it established for the first time the form
      of the 'catenary of equal strength'. The classical catenary is a uniform flexible
      chain or cable hanging freely under gravity between supports. The 'catenary of
      equal strength' is the form of a cable whose cross-sectional area is made
      proportional to the tension at each point, so that the tensile stress is uniform
      throughout. In this paper I provide a sketch of the lives and achievements of
      Gilbert and Telford, and of their interaction over the Menai Bridge. There
      follows a commentary on Gilbert's 1826 paper, and on his two related
      publications; and a brief sketch of the earlier history of the catenary. I then
      describe the development of the suspension bridge up to the present time.
      Finally, I discuss relations between mathematical analysts and practical
      engineers. This commentary was written to celebrate the 350th anniversary of the
      journal Philosophical Transactions of the Royal Society. 

PMID- 25750154
TI  - Celebrating 350 years of Philosophical Transactions: physical sciences papers.

PMID- 25750155
TI  - '...a paper ...I hold to be great guns': a commentary on Maxwell (1865) 'A
      dynamical theory of the electromagnetic field'.
AB  - Maxwell's great paper of 1865 established his dynamical theory of the
      electromagnetic field. The origins of the paper lay in his earlier papers of
      1856, in which he began the mathematical elaboration of Faraday's researches into
      electromagnetism, and of 1861-1862, in which the displacement current was
      introduced. These earlier works were based upon mechanical analogies. In the
      paper of 1865, the focus shifts to the role of the fields themselves as a
      description of electromagnetic phenomena. The somewhat artificial mechanical
      models by which he had arrived at his field equations a few years earlier were
      stripped away. Maxwell's introduction of the concept of fields to explain
      physical phenomena provided the essential link between the mechanical world of
      Newtonian physics and the theory of fields, as elaborated by Einstein and others,
      which lies at the heart of twentieth and twenty-first century physics. This
      commentary was written to celebrate the 350th anniversary of the journal
      Philosophical Transactions of the Royal Society. 

PMID- 25750156
TI  - Electrolysis within anaerobic bioreactors stimulates breakdown of toxic products
      from azo dye treatment.
AB  - Azo dyes are the most widely used coloring agents in the textile industry, but
      are difficult to treat. When textile effluents are discharged into waterways, azo
      dyes and their degradation products are known to be environmentally toxic. An
      electrochemical system consisting of a graphite-plate anode and a stainless-steel
      mesh cathode was placed into a lab-scale anaerobic bioreactor to evaluate the
      removal of an azo dye (Direct Black 22) from synthetic textile wastewater. At
      applied potentials of 2.5 and 3.0 V when water electrolysis occurs, no
      improvement in azo dye removal efficiency was observed compared to the control
      reactor (an integrated system with electrodes but without an applied potential).
      However, applying such electric potentials produces oxygen via electrolysis and
      promoted the aerobic degradation of aromatic amines, which are toxic,
      intermediate products of anaerobic azo dye degradation. The removal of these
      amines indicates a decrease in overall toxicity of the effluent from a single
      stage anaerobic bioreactor, which warrants further optimization in anaerobic
      digestion. 

PMID- 25750157
TI  - Accelerometer-assessed physical activity and sedentary time among colon cancer
      survivors: associations with psychological health outcomes.
AB  - PURPOSE: The purpose of this study was to determine associations of objectively
      assessed moderate-to-vigorous intensity physical activity (MVPA) and sedentary
      time with psychological health outcomes including depression symptoms, anxiety
      symptoms, and overall satisfaction with life in colon cancer survivors. METHODS:
      Colon cancer survivors (N = 180) from Alberta, Canada (n = 91), and Western
      Australia (n = 89) completed a mailed survey that assessed depression symptom
      severity, state anxiety, and satisfaction with life (SWL). Sedentary time and
      MVPA were assessed using the Actigraph((r)) GT3X+ accelerometer (60-s epochs) via
      a 7-day monitoring protocol. MVPA and sedentary time were corrected for wear time
      and then examined as quartiles (Q). Multivariate analysis of variance was used to
      examine associations of MVPA and sedentary time with psychological health.
      RESULTS: There was a significant association between psychological health
      outcomes and objectively assessed MVPA [Wilks' lambda = 0.886, F(3382.2) = 2.156,
      p = 0.024] that suggested a small and significant association between MVPA and
      SWL (p = 0.032). A significant multivariate analysis of variance (MANOVA) [Wilks'
      lambda = 0.945, F(3159) = 3.1, p = 0.028] suggested participants meeting
      guidelines reported significantly fewer anxiety symptoms (M(diff) = -1.23, p =
      0.027) and higher perceptions of SWL (M(diff) = 3.0, p = 0.008). No significant
      associations emerged for sedentary time [Wilks' lambda = 0.956, F(9382.3) =
      0.788, p = 0.628]. CONCLUSIONS: Contrary to previously published research using
      self-reports, objectively assessed MVPA and sedentary time were not associated
      with depression symptoms. Objectively assessed MVPA was associated with SWL and
      anxiety outcomes in colon cancer survivors. IMPLICATIONS FOR CANCER SURVIVORS:
      Colon cancer survivors should continue to engage in regular and sustained MVPA
      for the accrual of psychological health benefits.

PMID- 25750158
TI  - Hormonal dysfunction is frequent in cancer survivors treated with radiotherapy to
      the head and neck region.
AB  - PURPOSE: Cancer treatment may lead to hormonal dysfunction. Therefore, we
      assessed the prevalence of dysfunction in four hormonal axes among long-term
      cancer survivors who received radiotherapy to the head and neck region and
      analyzed associations between hormonal status and clinical variables. METHODS: We
      included 140 cancer survivors who received radiotherapy to the head and neck
      region, either locally or through total body irradiation after a diagnosis of
      lymphoma, plasmacytoma/multiple myeloma, or carcinoma of the epipharynx.
      Radiation doses to the pituitary gland and thyroid gland were estimated, and
      blood samples were collected to analyze hormonal levels. RESULTS: At a median of
      16 years after their cancer diagnosis, 46% of cancer survivors showed dysfunction
      in one hormonal axis, 24% had dysfunction in two axes, and 3% had dysfunction in
      three axes. Twenty cancer survivors (14%) had hormone levels consistent with
      pituitary dysfunction. Cancer survivors who had received an estimated 30 Gray
      (Gy) or more to the pituitary gland had an increased risk for pituitary
      dysfunction in one of the hormonal axes (odds ratio [OR] 3.16, confidence
      interval [CI] 1.02-9.87, p = 0.047) and for growth hormone dysfunction alone (OR
      2.96, CI 1.02-8.55, p = 0.045). CONCLUSIONS: Abnormal hormone values are frequent
      after radiotherapy to the head and neck region. IMPLICATIONS FOR CANCER
      SURVIVORS: Screening for hormonal dysfunction during follow-up might be
      indicated.

PMID- 25750159
TI  - A study of the human skin-whitening effects of resveratryl triacetate.
AB  - Resveratrol has a variety of bioactivities that include its anti-melanogenic
      effects, but its use in cosmetics has been challenging partly because of its
      chemical instability. Resveratryl triacetate (RTA) is a prodrug that can enhance
      stability. The purpose of this study was to examine the skin safety and whitening
      effects of RTA in human subjects. The primary skin irritation potentials of RTA
      and resveratrol were tested at 0.1 and 0.5 % on human subjects. Resveratrol at a
      concentration of 0.5 % induced weak skin irritation, whereas RTA did not induce
      any skin responses. The skin-whitening efficacy of a cosmetic formulation
      containing 0.4 % RTA was evaluated in two different test models. In the
      artificial tanning model, the test product and the control product were applied
      twice daily to the skin of the forearms of 22 human subjects after pigmentation
      induction by ultraviolet irradiation. Applying the test and the control products
      to the artificial tanning model for 8 weeks increased the individual topology
      angles (ITA degrees ) by 17.06 and 13.81 %, respectively, a difference that was
      statistically significant (p < 0.05). In the hyperpigmentation model, the test
      product and the control product were applied twice daily to the faces of 21 human
      subjects. The averaged intensity of the hyperpigmented spots decreased by 2.67 %
      in the test group and 1.46 % in the control group, a difference that was
      statistically significant (p < 0.05). Therefore, RTA incorporated into cosmetic
      formulations can whiten human skin without inducing skin irritation.

PMID- 25750160
TI  - Using urine drug testing to support healthy boundaries in clinical care.
AB  - Risk management is first and foremost about protecting patients. This article
      will examine risk management in general, and urine drug testing (UDT) in
      particular, as core constituents in an effective, comprehensive risk management
      strategy. The article will explore UDT as a tool to help practitioners and
      patients make better choices in the clinical management of chronic pain. How one
      makes these difficult clinical decisions based on UDT results as well common
      barriers encountered in conducting patient-centered UDT will also be examined. 

PMID- 25750161
TI  - Immunoassay in healthcare testing applications.
AB  - Immunoassay is used extensively for drug testing in pain management. Drug testing
      for the purpose of compliance monitoring is fundamentally different from forensic
      applications, which may rely on immunoassay screening to rapidly identify
      "negative" samples. In clinical settings, focus is shifted from identification of
      select drugs of abuse with low positivity rates to detection of a wide variety of
      licit and illicit compounds with expected high positivity rates. The primary drug
      classes of interest in this population, opioids and benzodiazepines, require
      special testing considerations when immunoassay is used. This review highlights
      the performance characteristics of immunoassay, with special emphasis on
      prescription drug classes and testing at the point-of-care. 

PMID- 25750162
TI  - A primer on definitive gas and liquid chromatography drug testing: What
      clinicians need to know.
AB  - OBJECTIVE: To describe the differences between mass spectrometry technologies and
      compare and contrast them with immunoassay techniques of urine drug testing
      (UDT). Highlight the potential importance of the differences among these
      technologies for clinicians so as to allow them make decisions in their use in
      patient care. METHODS: Review of mass spectrometry techniques, including gas
      chromatography, liquid chromatography, and time-of-flight techniques. RESULTS:
      The potential clinical implications of these technologies stemming from their
      scope and accuracy are presented. SIGNIFICANCE: UDT is an important clinical
      tool, though there are differences in technology and testing processes with
      important implications for clinical decision making. It is crucial, therefore,
      that clinicians have an understanding of the technologies behind the tests they
      order, so that their interpretation and use of results are based on an
      understanding of the strengths and weaknesses of the technologies used.

PMID- 25750163
TI  - Choosing the right laboratory: a review of clinical and forensic toxicology
      services for urine drug testing in pain management.
AB  - Urine drug testing (UDT) services are provided by a variety of clinical,
      forensic, and reference/specialty laboratories. These UDT services differ based
      on the principal activity of the laboratory. Clinical laboratories provide
      testing primarily focused on medical care (eg, emergency care, inpatients, and
      outpatient clinics), whereas forensic laboratories perform toxicology tests
      related to postmortem and criminal investigations, and drug-free workplace
      programs. Some laboratories now provide UDT specifically designed for monitoring
      patients on chronic opioid therapy. Accreditation programs for clinical
      laboratories have existed for nearly half a century, and a federal certification
      program for drug-testing laboratories was established in the 1980s. Standards of
      practice for forensic toxicology services other than workplace drug testing have
      been established in recent years. However, no accreditation program currently
      exists for UDT in pain management, and this review considers several aspects of
      laboratory accreditation and certification relevant to toxicology services, with
      the intention to provide guidance to clinicians in their selection of the
      appropriate laboratory for UDT surveillance of their patients on opioid therapy. 

PMID- 25750165
TI  - Specimen validity testing in urine drug monitoring of medications and illicit
      drugs: clinical implications.
AB  - OBJECTIVE: To discuss the importance of specimen validity testing (SVT) in urine
      drug testing (UDT) and the clinical role it plays in identifying efforts to
      subvert the UDT process. METHODS: A discussion of the clinical impact of SVT is
      presented. RESULTS: A discussion of pH, specific gravity, creatinine, and
      oxidation for monitoring the adulteration of UDT samples is presented along with
      the clinical significance of such tests. SIGNIFICANCE: SVT has a significant
      place in healthcare efforts to measure patient adherence, behavior, and honesty
      in communication with clinicians. SVT is typically ordered by treating clinicians
      who use the results to make therapeutic decisions regarding specific medical
      problems of their patient, including those related to medication and illicit drug
      use. In the absence of SVT, a healthcare provider may fail to identify a
      patient's adulteration of their urine sample in an attempt at deceiving the
      provider. Moreover, the presence of some underlying medical conditions may
      obfuscate the UDT results.

PMID- 25750164
TI  - Treatment changes following aberrant urine drug test results for patients
      prescribed chronic opioid therapy.
AB  - BACKGROUND/OBJECTIVE: Urine drug testing (UDT) may be used to help screen for
      prescription opioid misuse. There are little data available describing usual pain
      care practices for patients who have aberrant UDT results. The goal of this
      research was to evaluate the clinical care for patients prescribed chronic opioid
      therapy (COT) and have an aberrant UDT. DESIGN: Retrospective cohort study.
      SETTING: VA Medical Center in the Pacific Northwest. PARTICIPANTS: Patients with
      chronic pain who were prescribed COT and had a UDT result that was positive for
      an illicit or nonprescribed substance. MAIN OUTCOME MEASURES: This was an
      exploratory study designed to document usual care practices. RESULTS:
      Participants' (n = 83) mean age was 49.5 (SD = 9.6) and 81.5 percent were male.
      The most common substances detected on UDT were marijuana (69 percent) or a
      nonprescribed opioid (25 percent); 18 percent had a UDT positive for two or more
      substances. Plans to modify treatment were documented in 69 percent of cases. The
      most common treatment change after aberrant UDT results was instituting more
      frequent UDTs, which occurred in 43 percent of cases. Clinicians documented plans
      to alter their opioid prescribing (eg, terminating opioids, requiring more
      frequent fills, changing opioid dose, or transitioning to another opioid) in 52
      percent of cases, but implemented these changes in only 24 percent. DISCUSSION:
      Current methods for optimizing treatment after obtaining aberrant UDT results
      should be enhanced. To improve the utility of UDT to reduce prescription opioid
      misuse, additional interventions and support for clinicians need to be developed
      and tested.

PMID- 25750166
TI  - Trends in drug use from urine drug testing of addiction treatment clients.
AB  - OBJECTIVE: Urine drug testing (UDT) can play an important role in the care of
      patients in recovery from addiction, and it has become necessary for providers
      and programs to utilize specific, accurate testing beyond what immunoassay (IA)
      provides. DESIGN: A database of addiction treatment and recovery programs was
      sampled to demonstrate national trends in drug abuse and to explore potential
      clinical implications of differing results due to the type of testing utilized.
      SETTING: Deidentified data was selected from a national laboratory testing
      company that had undergone liquid chromatography tandem mass spectrometry (LC
      MS/MS). PATIENTS/PARTICIPANTS: A total of 4,299 samples were selected for study.
      INTERVENTIONS: Descriptive statistics of the trends are presented. RESULTS: In
      total, 48.5 percent (n = 2,082) of the samples were deemed in full agreement
      between the practice reports and the results of LC-MS/MS testing. The remaining
      51.5 percent of samples fell into one of seven categories of unexpected results,
      with the most frequent being detection of an unreported prescription medication
      (n = 1,097). CONCLUSIONS: Results of UDT demonstrate that more than half of
      samples yield unexpected results from specimens collected in addiction treatment.
      When comparing results of IA and LC-MS/MS, it is important to consider the limits
      of IA in the detection of drug use by these patients.

PMID- 25750167
TI  - Drug testing and adherence monitoring in pain management: Oral fluid testing.
AB  - A review of the utility of oral fluid in drug testing and adherence monitoring in
      pain management is presented. The article includes a description of the "State of
      the Art"; drug deposition; advantages and drawbacks of oral fluid testing; and
      overall related literature. 

PMID- 25750168
TI  - FDA/DEA/PDMP/UDT: alphabet soup or sensible and integrated risk management?
AB  - OBJECTIVE: Both prescription drug monitoring programs (PDMP) and urine drug
      testing (UDT) are recommended as parts of an ongoing risk management approach for
      controlled substance prescribing. The authors provide an editorial and commentary
      to discuss the unique contributions of each to promote better clinical decision
      making for prescribers. DESIGN: A commentary is employed along with brief
      discussion comparing four states with an active PDMP in place to three states
      without an active PDMP as it relates back to findings on UDT in those states from
      a laboratory conducting liquid chromatography tandem mass spectrometry.
      CONCLUSIONS: The commentary focuses on the place of both tools (UDT and PDMP) in
      risk management efforts. The argument is made that relying on a PDMP alone would
      lead to clinical decisions that may miss a great deal of problematic or aberrant
      behaviors.

PMID- 25750169
TI  - Medication monitoring and drug testing ethics project.
AB  - In 2012, Duke University initiated a research project, funded by an unrestricted
      research grant from Millennium Laboratories, a drug testing company. The project
      focused on assessing the frequency and nature of questionable, unethical, and
      illegal business practices in the clinical drug testing industry and assessing
      the potential for establishing a business code of ethics. Laboratory leaders,
      clinicians, industry attorneys, ethicists, and consultants participated in the
      survey, were interviewed, and attended two face-to-face meetings to discuss a way
      forward. The study demonstrated broad acknowledgment of variations in the legal
      and regulatory environment, resulting in inconsistent enforcement of industry
      practices. Study participants expressed agreement that overtly illegal practices
      sometimes exist, particularly when laboratory representatives and clinicians
      discuss reimbursement, extent of testing, and potential business incentives with
      medical practitioners. Most respondents reported directly observing probable
      violations involving marketing materials, contracts, or, in the case of some
      individuals, directly soliciting people with offers of clinical supplies and
      other "freebies." While many study respondents were skeptical that voluntary
      standards alone would eliminate questionable business practices, most viewed
      ethics codes and credentialing as an important first step that could potentially
      mitigate uneven enforcement, while improving quality of care and facilitating
      preferred payment options for credentialed parties. Many were willing to
      participate in future discussions and industry-wide initiatives to improve the
      environment. 

PMID- 25750170
TI  - Evaluating motives: Two simple tests to identify and avoid entanglement in
      legally dubious urine drug testing schemes.
AB  - OBJECTIVE: This article educates healthcare practitioners on the legal framework
      prohibiting abusive practices in urine drug testing (UDT) in medical settings,
      discusses several profit-driven UDT schemes that have resulted in enforcement
      actions, and provides recommendations for best practices in UDT to comply with
      state and federal fraud and anti-kickback statutes. METHODS: The authors
      carefully reviewed and analyzed statutes, regulations, adivsory opinions, case
      law, court documents, articles from legal journals, and news articles. RESULTS:
      Certain facts-driven UDT arrangements tend to violate federal and state
      healthcare laws and regulations, including Stark law, the anti-kickback statute,
      the criminal health care fraud statute, and the False Claims Act. CONCLUSIONS:
      Healthcare practitioners who use UDT can help ensure that they are in compliance
      with applicable federal and state laws by evaluating whether their actions are
      motivated by providing proper care to their patients rather than by profits. They
      must avoid schemes that violate the spirit of the law while appearing to comply
      with the letter of the law. Such a simple self-evaluation of motive can reduce a
      practitioner's likelihood of civil fines and criminal liability.

PMID- 25750171
TI  - APRIL promotes breast tumor growth and metastasis and is associated with
      aggressive basal breast cancer.
AB  - APRIL (a proliferation-inducing ligand) is a cytokine of the tumor necrosis
      factor family associated mainly with hematologic malignancies. APRIL is also
      overexpressed in breast carcinoma tissue lesions, although neither its role in
      breast tumorigenesis nor the underlying molecular mechanism is known. Here, we
      show that several breast cancer cell lines express APRIL and both its receptors,
      B cell maturation antigen (BCMA) and transmembrane activator and CAML-interactor
      (TACI), independently of luminal or basal tumor cell phenotype, and that the
      mitogen-activated protein kinases p38, ERK1/2, and JNK1/2 are activated in
      response to APRIL. The inflammatory stimulus poly I:C, a toll-like receptor (TLR)
      3 ligand, enhanced APRIL secretion. Silencing experiments decreased cell
      proliferation, demonstrating that APRIL is a critical autocrine factor for breast
      tumor growth. Studies of 4T1 orthotopic breast tumors in APRIL transgenic mice
      showed that an APRIL-enriched environment increased tumor growth and promoted
      lung metastasis associated with enhanced tumor cell proliferation; BCMA and TACI
      expression suggests that both participate in these processes. We detected APRIL,
      BCMA and TACI in human luminal, triple-negative breast carcinomas and HER2 breast
      carcinomas, with increased levels in more aggressive basal tumors. APRIL was
      observed near Ki67(+) nuclei and was distributed heterogeneously in the cancer
      cells, in the leukocyte infiltrate, and in the myoepithelial layer adjacent to
      the tumor area; these results imply that APRIL provides proliferation signals to
      tumor cells through paracrine and autocrine signaling. Our study identifies
      participation of APRIL signaling in breast cancer promotion; we propose
      impairment of this pathway as a potential therapeutic strategy. 

PMID- 25750172
TI  - PU.1 downregulation in murine radiation-induced acute myeloid leukaemia (AML):
      from molecular mechanism to human AML.
AB  - The transcription factor PU.1, encoded by the murine Sfpi1 gene (SPI1 in humans),
      is a member of the Ets transcription factor family and plays a vital role in
      commitment and maturation of the myeloid and lymphoid lineages. Murine studies
      directly link primary acute myeloid leukaemia (AML) and decreased PU.1 expression
      in specifically modified strains. Similarly, a radiation-induced chromosome 2
      deletion and subsequent Sfpi1 point mutation in the remaining allele lead to
      murine radiation-induced AML. Consistent with murine data, heterozygous deletion
      of the SPI1 locus and mutation of the -14kb SPI1 upstream regulatory element were
      described previously in human primary AML, although they are rare events. Other
      mechanisms linked to PU.1 downregulation in human AML include TP53 deletion, FLT3
      ITD mutation and the recurrent AML1-ETO [t(8;21)] and PML-RARA [t(15;17)]
      translocations. This review provides an up-to-date overview on our current
      understanding of the involvement of PU.1 in the initiation and development of
      radiation-induced AML, together with recommendations for future murine and human
      studies. 

PMID- 25750173
TI  - Aberrantly expressed Fra-1 by IL-6/STAT3 transactivation promotes colorectal
      cancer aggressiveness through epithelial-mesenchymal transition.
AB  - The pro-inflammatory cytokine interleukin-6 (IL-6) in tumor microenvironment has
      been suggested to promote development and progression of colorectal cancer (CRC).
      However, the underlying molecular mechanisms remain elusive. In this study, we
      demonstrate that fos-related antigen-1 (Fra-1) plays a critical role in IL-6
      induced CRC aggressiveness and epithelial-mesenchymal transition (EMT). In CRC
      cell lines, the expression of Fra-1 gene was found significantly upregulated
      during IL-6-driven EMT process. The Fra-1 induction occurred at transcriptional
      level in a manner dependent on signal transducer and activator of transcription 3
      (STAT3), during which both phosphorylated and acetylated post-translational
      modifications were required for STAT3 activation to directly bind to the Fra-1
      promoter. Importantly, RNA interference-based attenuation of either STAT3 or Fra
      1 prevented IL-6-induced EMT, cell migration and invasion, whereas ectopic
      expression of Fra-1 markedly reversed the STAT3-knockdown effect and enhanced CRC
      cell aggressiveness by regulating the expression of EMT-promoting factors (ZEB1,
      Snail, Slug, MMP-2 and MMP-9). Furthermore, Fra-1 levels were positively
      correlated with the local invasion depth as well as lymph node and liver
      metastasis in a total of 229 CRC patients. Intense immunohistochemical staining
      of Fra-1 was observed at the tumor marginal area adjacent to inflammatory cells
      and in parallel with IL-6 secretion and STAT3 activation in CRC tissues.
      Together, this study proposes the existence of an aberrant IL-6/STAT3/Fra-1
      signaling axis leading to CRC aggressiveness through EMT induction, which
      suggests novel therapeutic opportunities for the malignant disease. 

PMID- 25750175
TI  - Improvements in progression-free and overall survival due to the use of anti
      angiogenic agents in gynecologic cancers.
AB  - OPINION STATEMENT: In ovarian cancer (OC), the best established anti-angiogenic
      drug, bevacizumab, has demonstrated only modest prolonged progression free
      survival (PFS) and no increased overall survival (OS). The unanswered question is
      in which clinical situation bevacizumab might benefit ovarian cancer patients
      most. The cost-benefit analysis in the primary treatment was found not to be
      favorable but the use in the recurrent OC setting might be more compelling. Multi
      targeted anti-angiogenic tyrosine kinase inhibitors (TKI) such as cediranib and
      pazopanib have shown some therapeutic benefits with improvements of PFS and OS in
      patients with platinum-sensitive as well as resistant OC, in whom there is a
      major need for novel therapies. Very promising is also the observed improvement
      of PFS in recurrent OC in patients when combining cediranib with the PARP
      inhibitor olaparib without giving additional chemotherapy. The anti-angiogenic
      agent trebananib has achieved similar results like TKI, but has a favorable
      toxicity profile which does not overlap with those of VEGF inhibitors. In
      cervical cancer the addition of bevacizumab to combination chemotherapy in
      patients with recurrent, persistent or metastatic chemotherapy-naive disease
      results in a significant increase in OS. Considering the lack of therapeutic
      options in this difficult clinical setting, the inclusion of bevacizumab most
      likely will become a new standard for recurrent cervical cancer. In uterine
      sarcomas as very aggressive malignancies with a substantial need for better
      therapies the observed improved PFS with sorafenib warrants further
      investigation. No data showing a convincing improvement of survival in
      endometrial cancer have been presented yet. In view of the limited PFS and OS
      benefit observed with anti-angiogenics in gynecologic oncology, increased
      morbidity due to side effects of this treatment resulting in loss of quality of
      life and also substantial costs have to be taken into consideration. Thorough
      case selection based on molecular subgrouping of gynecologic cancers will
      therefore be a prerequisite for future anti-angiogenic therapy. This will require
      the integration of molecular diagnostics which still have to be developed and
      standardized.

PMID- 25750174
TI  - Activation of peroxisome proliferator-activated receptor alpha induces lysosomal
      biogenesis in brain cells: implications for lysosomal storage disorders.
AB  - Lysosomes are ubiquitous membrane-enclosed organelles filled with an acidic
      interior and are central to the autophagic, endocytic, or phagocytic pathway. In
      contrast to its classical function as the waste management machinery, lysosomes
      are now considered to be an integral part of various cellular signaling
      processes. The diverse functionality of this single organelle requires a very
      complex and coordinated regulation of its activity with transcription factor EB
      (TFEB), a master regulator of lysosomal biogenesis, at its core. However,
      mechanisms by which TFEB is regulated are poorly understood. This study
      demonstrates that gemfibrozil, an agonist of peroxisome proliferator-activated
      receptor (PPAR) alpha, alone and in conjunction with all-trans-retinoic acid is
      capable of enhancing TFEB in brain cells. We also observed that PPARalpha, but
      not PPARbeta and PPARgamma, is involved in gemfibrozil-mediated up-regulation of
      TFEB. Reporter assay and chromatin immunoprecipitation studies confirmed the
      recruitment of retinoid X receptor alpha, PPARalpha, and PGC1alpha on the PPAR
      binding site on the Tfeb promoter as well. Subsequently, the drug-mediated
      induction of TFEB caused an increase in lysosomal protein and the lysosomal
      abundance in cell. Collectively, this study reinforces the link between lysosomal
      biogenesis and lipid metabolism with TFEB at the crossroads. Furthermore,
      gemfibrozil may be of therapeutic value in the treatment of lysosomal storage
      disorders in which autophagy-lysosome pathway plays an important role. 

PMID- 25750176
TI  - A privacy preserving secure and efficient authentication scheme for telecare
      medical information systems.
AB  - The Telecare medical information system (TMIS) presents effective healthcare
      delivery services by employing information and communication technologies. The
      emerging privacy and security are always a matter of great concern in TMIS.
      Recently, Chen at al. presented a password based authentication schemes to
      address the privacy and security. Later on, it is proved insecure against various
      active and passive attacks. To erase the drawbacks of Chen et al.'s anonymous
      authentication scheme, several password based authentication schemes have been
      proposed using public key cryptosystem. However, most of them do not present pre
      smart card authentication which leads to inefficient login and password change
      phases. To present an authentication scheme with pre-smart card authentication,
      we present an improved anonymous smart card based authentication scheme for TMIS.
      The proposed scheme protects user anonymity and satisfies all the desirable
      security attributes. Moreover, the proposed scheme presents efficient login and
      password change phases where incorrect input can be quickly detected and a user
      can freely change his password without server assistance. Moreover, we
      demonstrate the validity of the proposed scheme by utilizing the widely-accepted
      BAN (Burrows, Abadi, and Needham) logic. The proposed scheme is also comparable
      in terms of computational overheads with relevant schemes. 

PMID- 25750177
TI  - Development of de novo major involvement during follow-up in Behcet's syndrome.
AB  - The primary aim of the study was to evaluate the incidence of de novo major
      involvement during follow-up in a cohort of patients with Behcet's syndrome (BS);
      the secondary aim was to analyse the epidemiological profile and the long-term
      outcome of those patients who developed new major involvement. Among our cohort
      of 120 BS patients, we evaluated all subjects who had no major organ involvement
      during the early years of their disease; specifically, at disease onset, the 52%
      of the cohort presented a prevalent mucocutaneous involvement. The primary
      outcomes were represented by the following: Hatemi et al. (Rheum Dis Clin North
      Am 39(2):245-61, 2013) the incidence of de novo major involvement during the
      follow-up and Hatemi et al. (Clin Exp Rheumatol 32(4 Suppl 84):S112-22, 2014) the
      use of immunosuppressive drugs during the follow-up. We have defined the
      development of de novo major involvement during the follow-up as the occurrence
      of severe ocular, vascular or CNS involvement after a latency period from the
      diagnosis of at least 3 years. Among 62 patients characterized by a mild onset of
      disease, we observed that after at least 3 years from the diagnosis, 21 BS
      patients (34%) still developed serious morbidities. Specifically, three patients
      developed ocular involvement, nine patients developed neurological involvement
      and nine patients presented vascular involvement. Comparing main epidemiological
      and clinical findings of the two groups, we observed that patients who developed
      de novo major involvement were more frequently males and younger; furthermore,
      95% of these patients were characterized by a young onset of disease (p < 0.001).
      Being free of major organ complication in the first years of BS is not necessary
      a sign of a favourable outcome. Globally, the development of de novo major
      involvement during the coursfce of BS suggests that a tight control is strongly
      recommended during the course of the disease.

PMID- 25750178
TI  - An Arabidopsis Transcriptional Regulatory Map Reveals Distinct Functional and
      Evolutionary Features of Novel Transcription Factors.
AB  - Transcription factors (TFs) play key roles in both development and stress
      responses. By integrating into and rewiring original systems, novel TFs
      contribute significantly to the evolution of transcriptional regulatory networks.
      Here, we report a high-confidence transcriptional regulatory map covering 388 TFs
      from 47 families in Arabidopsis. Systematic analysis of this map revealed the
      architectural heterogeneity of developmental and stress response subnetworks and
      identified three types of novel network motifs that are absent from unicellular
      organisms and essential for multicellular development. Moreover, TFs of novel
      families that emerged during plant landing present higher binding specificities
      and are preferentially wired into developmental processes and these novel network
      motifs. Further unveiled connection between the binding specificity and wiring
      preference of TFs explains the wiring preferences of novel-family TFs. These
      results reveal distinct functional and evolutionary features of novel TFs,
      suggesting a plausible mechanism for their contribution to the evolution of
      multicellular organisms. 

PMID- 25750179
TI  - Evolutionary Advantage Conferred by an Eukaryote-to-Eukaryote Gene Transfer Event
      in Wine Yeasts.
AB  - Although an increasing number of horizontal gene transfers have been reported in
      eukaryotes, experimental evidence for their adaptive value is lacking. Here, we
      report the recent transfer of a 158-kb genomic region between Torulaspora
      microellipsoides and Saccharomyces cerevisiae wine yeasts or closely related
      strains. This genomic region has undergone several rearrangements in S.
      cerevisiae strains, including gene loss and gene conversion between two tandemly
      duplicated FOT genes encoding oligopeptide transporters. We show that FOT genes
      confer a strong competitive advantage during grape must fermentation by
      increasing the number and diversity of oligopeptides that yeast can utilize as a
      source of nitrogen, thereby improving biomass formation, fermentation efficiency,
      and cell viability. Thus, the acquisition of FOT genes has favored yeast
      adaptation to the nitrogen-limited wine fermentation environment. This finding
      indicates that anthropic environments offer substantial ecological opportunity
      for evolutionary diversification through gene exchange between distant yeast
      species. 

PMID- 25750180
TI  - Asymmetric Context-Dependent Mutation Patterns Revealed through Mutation
      Accumulation Experiments.
AB  - Despite the general assumption that site-specific mutation rates are independent
      of the local sequence context, a growing body of evidence suggests otherwise. To
      further examine context-dependent patterns of mutation, we amassed 5,645
      spontaneous mutations in wild- type (WT) and mismatch-repair deficient (MMR(-))
      mutation-accumulation (MA) lines of the gram-positive model organism Bacillus
      subtilis. We then analyzed>7,500 spontaneous base-substitution mutations across
      B. subtilis, Escherichia coli, and Mesoplasma florum WT and MMR(-) MA lines,
      finding a context-dependent mutation pattern that is asymmetric around the origin
      of replication. Different neighboring nucleotides can alter site-specific
      mutation rates by as much as 75-fold, with sites neighboring G:C base pairs or
      dimers involving alternating pyrimidine-purine and purine-pyrimidine nucleotides
      having significantly elevated mutation rates. The influence of context-dependent
      mutation on genome architecture is strongest in M. florum, consistent with the
      reduced efficiency of selection in organisms with low effective population size.
      If not properly accounted for, the disparities arising from patterns of context
      dependent mutation can significantly influence interpretations of positive and
      purifying selection. 

PMID- 25750181
TI  - Interfaces between allergen structure and diagnosis: know your epitopes.
AB  - Allergy diagnosis is based on the patient's clinical history and can be
      strengthened by tests that confirm the origin of sensitization. In the past 25
      years, these tests have evolved from the exclusive in vivo or in vitro use of
      allergen extracts, to complementary molecular-based diagnostics that rely on in
      vitro measurements of IgE reactivity to individual allergens. For this to occur,
      an increase in our understanding of the molecular structure of allergens, largely
      due to the development of technologies such as molecular cloning and expression
      of recombinant allergens, X-ray crystallography, or nuclear magnetic resonance
      (NMR), has been essential. New in vitro microarray or multiplex systems are now
      available to measure IgE against a selected panel of purified natural or
      recombinant allergens. The determination of the three-dimensional structure of
      allergens has facilitated detailed molecular studies, including the analysis of
      antigenic determinants for diagnostic purposes. 

PMID- 25750182
TI  - Correlation between systemic lupus erythematosus and cytomegalovirus infection
      detected by different methods.
AB  - Human cytomegalovirus (HCMV), a beta-herpes virus subfamily member, leads to a
      lifelong, latent infection in most humans, but the correlation between HCMV
      infection and systemic lupus erythematosus (SLE) remains controversial. We
      analyzed the relevance of HCMV infection in SLE by analyzing the peripheral blood
      leukocytes (PBLs) and serum samples of 60 patients with SLE and 111 healthy
      individuals. HCMV genes UL55 and UL138 were detected in PBLs by polymerase chain
      reaction (PCR), and HCMV-specific serum IgG and IgM antibodies were investigated
      by enzyme-linked immunosorbent assay. The relationship between cellular HCMV
      infection in PBLs and common clinical indicators of SLE was further explored.
      Data indicated that the frequency of positive IgG and IgM anti-CMV antibodies was
      not significantly different in SLE patients and controls. However, compared to
      the healthy controls, the titers of IgG and IgM anti-CMV antibodies in SLE
      patients were significantly higher. The detection of cellular HCMV infection
      showed that almost all subjects were positive for UL138 gene in PBLs, but the
      positivity for UL55 gene was lower in PBLs. HCMV UL138 detection in PBLs was
      highly consistent with the frequency of the HCMV-specific IgG test and did not
      show significant difference in SLE patients and healthy controls. However,
      compared with that in healthy people, the positivity rate for cellular HCMV UL55
      detection was significantly higher in SLE patients (P < 0.001). In addition,
      cellular HCMV UL55 with positive detection in PBLs was associated with
      significantly different clinical characteristics of SLE than that with negative
      detection. In conclusion, our data confirmed that the HCMV infection was related
      to the development of SLE. Especially, some clinical strains or substrains of
      HCMV, such as containing the UL55 gene in HCMV's genome, might play a vital role
      in the development of SLE. 

PMID- 25750183
TI  - Low-molecular-weight adiponectin is more closely associated with disease activity
      of rheumatoid arthritis than other adiponectin multimeric forms.
AB  - Adiponectin is divided into high-molecular-weight (HMW), medium-molecular-weight
      (MMW), and low-molecular-weight (LMW) forms. These forms differ not only in the
      number of adiponectin molecules but also in their biological activity. There are
      conflicting findings regarding the role of adiponectin in rheumatoid arthritis
      (RA). Moreover, few reports have described the relationships between serum
      adiponectin multimers levels and RA. Therefore, we examined the association of
      total adiponectin and its multimers with RA. Two study groups were examined: 180
      recently diagnosed untreated RA patients with disease duration less than 1 year
      (RA group) and 160 age- and sex-matched control subjects (control group). RA
      related factors, blood pressure, body mass index, glucose, complete lipid
      profile, and adiponectin multimers were measured. The levels of total adiponectin
      and each multimer of adiponectin were significantly lower in the RA than in the
      control (P < 0.01). Serum levels of total, HMW, MMW, and LMW were positively
      correlated with triglycerides levels and negatively correlated with the Disease
      Activity Score for 28 joints (DAS28). Multivariate regression analysis showed
      that total, HMW, and MMW adiponectin were independently associated with serum
      triglycerides level. LMW adiponectin was independently correlated with serum
      triglycerides level and DAS28. The decreased LMW adiponectin levels may be
      associated with disease activity of RA.

PMID- 25750184
TI  - Increased levels of HSPA5 in the serum of patients with inflammatory myopathies-
      preliminary findings.
AB  - Endoplasmic reticulum (ER) stress is suggested to play an important role in the
      pathogenesis of myositis recently. The aim of this study was to investigate the
      serum concentration of an ER stress-specific chaperone protein HSPA5 in patients
      with inflammatory myopathies. Forty-five patients (27 with polymyositis (PM) and
      18 with dermatomyositis (DM)) were included in the study, and all received
      prednisone therapy. Serum samples were collected from each patient before and
      after prednisone treatment. Serum HSPA5 levels were detected by enzyme-linked
      immunosorbent assays. The serum level of HSPA5 was significantly higher in
      myositis patients than in controls. In addition, the concentrations in the DM
      subgroup were significantly higher than in the PM groups. Serum HSPA5 levels were
      positively correlated with creatine kinase (CK) and C-reactive protein (CRP) in
      PM patients. In patients with DM, the serum HSPA5 concentrations were also found
      significantly correlated with CK, but not with CRP. After prednisone treatment,
      serum HSPA5 levels significantly decreased compared to baseline in steroid
      responders, but no marked decrease was observed in steroid non-responders. Serum
      HSPA5 is increased in patients with DM and PM. Increased concentrations of HSPA5
      in serum may reflect the enhanced ER stress in muscle tissue. Decrease in serum
      HSPA5 levels appears in patients with clinical remission; therefore, HSPA5 may be
      a potential biomarker for inflammatory myopathies.

PMID- 25750185
TI  - Characterization of Peptides from Capsicum annuum Hybrid Seeds with Inhibitory
      Activity Against alpha-Amylase, Serine Proteinases and Fungi.
AB  - Over the last several years, the activity of antimicrobial peptides (AMPs),
      isolated from plant species, against different microorganisms has been
      demonstrated. More recently, some of these AMPs have been described as potent
      inhibitors of alpha-amylases and serine proteinases from insects and mammals. The
      aim of this work was to obtain AMPs from protein extracts of a hybrid Capsicum
      (Ikeda * UENF 1381) seeds and to evaluate their microbial and enzyme inhibitory
      activities. Initially, proteins were extracted from the Capsicum hybrid seeds in
      buffer (sodium phosphate pH 5.4,) and precipitated with ammonium sulfate (90%
      saturated). Extract of hybrid seeds was subjected to size exclusion
      chromatography, and three fractions were obtained: S1, S2 and S3. The amino acid
      sequence, obtained by mass spectrometry, of the 6 kDa peptide from the S3
      fraction, named HyPep, showed 100% identity with PSI-1.2, a serine protease
      inhibitor isolated from C. annuum seeds, however the bifunctionality of this
      inhibitor against two enzymes is being shown for the first time in this work. The
      S3 fraction showed the highest antifungal activity, inhibiting all the yeast
      strains tested, and it also exhibited inhibitory activity against human salivary
      and Callosobruchus maculatus alpha-amylases as well as serine proteinases.

PMID- 25750187
TI  - Effects of the polyphenol resveratrol on contractility of human term pregnant
      myometrium.
AB  - The ideal agent for prevention and treatment of uterine abnormal contractility
      has not been found. The polyphenol resveratrol possesses a wide spectrum of
      pharmacologic properties, but its influence on the contractility of human
      myometrium is not defined. The present study evaluated the effect of resveratrol
      on the oxytocin-induced contractions of human term pregnant myometrium in vitro
      and the contribution of different K(+) channels to resveratrol action.
      Resveratrol induced a concentration-dependent relaxation of myometrium
      contractions (pD2 value and maximal responses were 4.52 and 82.25%,
      respectively). Glibenclamide, a selective blocker of ATP-sensitive (KATP),
      iberiotoxin, a selective blockers of big-calcium sensitive (BK(Ca)) and 4
      aminopiridine, a non-selective blocker of voltage-sensitive (Kv) channels induced
      a significant shift to the right of the concentration-response curves of
      resveratrol. Inhibition achieved by 0.1 mM resveratrol was insensitive to all
      K(+) channel blockers. A K(+) channel opener, pinacidil, inhibited oxytocin
      induced contractions of pregnant myometrium with comparable potency and efficacy
      to resveratrol (pD2 values and maximal relaxation were 4.52 and 83.67%,
      respectively). Based on K(+) channel opener/blocker affinities, it appears that
      the inhibitory response of resveratrol involves different myometrial K(+)
      channels. When applied in high concentrations, resveratrol has an additional K(+)
      channel-independent mechanism(s) of action. Furthermore, immunohistochemistry
      staining and western blot analyses detected the presence and distribution of
      KATP, BK(Ca) and Kv channel proteins in pregnant myometrium.

PMID- 25750186
TI  - Sarcopenic obesity and the pathogenesis of exercise intolerance in heart failure
      with preserved ejection fraction.
AB  - Heart failure with preserved ejection fraction (HFpEF) is the most common form of
      heart failure (HF) in older adults. The primary chronic symptom in patients with
      HFpEF, even when well compensated, is severe exercise intolerance. Cardiac and
      peripheral functions contribute equally to exercise intolerance in HFpEF, though
      the latter has been the focus of fewer studies. Of note, multiple studies with
      exercise training have shown that exercise intolerance can improve significantly
      in the absence of improvements in exercise cardiac output, indicating a role of
      peripheral, noncardiac adaptations. In addition, clinical drug trials performed
      to date in HFpEF, all of which have focused on influencing cardiovascular
      function, have not been positive on primary clinical outcomes and most have not
      improved exercise capacity. Mounting evidence indicates that sarcopenic obesity,
      characterized by the coexistence of excess fat mass and decreased muscle mass,
      could contribute to the pathophysiology of exercise intolerance in older HFpEF
      patients and may provide avenues for novel treatments. 

PMID- 25750188
TI  - Role of secreted modular calcium-binding protein 1 (SMOC1) in transforming growth
      factor beta signalling and angiogenesis.
AB  - AIMS: Secreted modular calcium-binding protein 1 (SMOC1) is a matricellular
      protein that potentially interferes with growth factor receptor signalling. The
      aim of this study was to determine how its expression is regulated in endothelial
      cells and its role in the regulation of endothelial cell function. METHODS AND
      RESULTS: SMOC1 was expressed by native murine endothelial cells as well as by
      cultured human, porcine, and murine endothelial cells. SMOC1 expression in
      cultured cells was increased by hypoxia via the down-regulation of miR-223, and
      SMOC1 expression was increased in lungs from miR-223-deficient mice. Silencing
      SMOC1 (small interfering RNA) attenuated endothelial cell proliferation,
      migration, and sprouting in in vitro angiogenesis assays. Similarly endothelial
      cell sprouting from aortic rings ex vivo as well as postnatal retinal
      angiogenesis in vivo was attenuated in SMOC1(+/-) mice. In endothelial cells,
      transforming growth factor (TGF)-beta signalling via activin-like kinase (ALK) 5
      leads to quiescence, whereas TGF-beta signalling via ALK1 results in endothelial
      cell activation. SMOC1 acted as a negative regulator of ALK5/SMAD2 signalling,
      resulting in altered alpha2 integrin levels. Mechanistically, SMOC1 associated
      (immunohistochemistry, proximity ligation assay, and co-immunoprecipitation) with
      endoglin; an endothelium-specific type III auxiliary receptor for the TGF-beta
      super family and the effects of SMOC1 down-regulation on SMAD2 phosphorylation
      were abolished by the down-regulation of endoglin. CONCLUSION: These results
      indicate that SMOC1 is an ALK5 antagonist produced by endothelial cells that tips
      TGF-beta signalling towards ALK1 activation, thus promoting endothelial cell
      proliferation and angiogenesis.

PMID- 25750189
TI  - In vivo assessment of cardiac metabolism and function in the abdominal aortic
      banding model of compensated cardiac hypertrophy.
AB  - AIMS: Left ventricular hypertrophy is an adaptive response of the heart to
      chronic mechanical overload and can lead to functional deterioration and heart
      failure. Changes in cardiac energy metabolism are considered as key to the
      hypertrophic remodelling process. The concurrence of obesity and hypertrophy has
      been associated with contractile dysfunction, and this work therefore aimed to
      investigate the in vivo structural, functional, and metabolic remodelling that
      occurs in the hypertrophied heart in the setting of a high-fat, high-sucrose,
      Western diet (WD). METHODS AND RESULTS: Following induction of cardiac
      hypertrophy through abdominal aortic banding, male Sprague Dawley rats were
      exposed to either a standard diet or a WD (containing 45% fat and 16% sucrose)
      for up to 14 weeks. Cardiac structural and functional characteristics were
      determined by CINE MRI, and in vivo metabolism was investigated using
      hyperpolarized (13)C-labelled pyruvate. Cardiac hypertrophy was observed at all
      time points, irrespective of dietary manipulation, with no evidence of cardiac
      dysfunction. Pyruvate dehydrogenase flux was unchanged in the hypertrophied
      animals at any time point, but increased incorporation of the (13)C label into
      lactate was observed by 9 weeks and maintained at 14 weeks, indicative of
      enhanced glycolysis. CONCLUSION: Hypertrophied hearts revealed little evidence of
      a switch towards increased glucose oxidation but rather an uncoupling of
      glycolytic metabolism from glucose oxidation. This was maintained under
      conditions of dietary stress provided by a WD but, at this compensated phase of
      hypertrophy, did not result in any contractile dysfunction.

PMID- 25750190
TI  - Peptidyl-prolyl isomerases: a full cast of critical actors in cardiovascular
      diseases.
AB  - Peptidyl-prolyl cis-trans-isomerases are a highly conserved family of
      immunophilins. The three peptidyl-prolyl cis-trans-isomerase subfamilies are
      cyclophilins, FK-506-binding proteins, and parvulins. Peptidyl-prolyl cis-trans
      isomerases are expressed in multiple human tissues and regulate different
      cellular functions, e.g. calcium handling, protein folding, and gene expression.
      Moreover, these subfamilies have been shown to be consistently involved in
      several cardiac and vascular diseases including heart failure, arrhythmias,
      vascular stenosis, endothelial dysfunction, atherosclerosis, and hypertension.
      This review provides a concise description of the peptidyl-prolyl cis-trans
      isomerases and presents an incisive selection of studies focused on their
      relationship with cardiovascular diseases. 

PMID- 25750192
TI  - Inhibition of indoleamine 2,3-dioxygenase promotes vascular inflammation and
      increases atherosclerosis in Apoe-/- mice.
AB  - AIMS: Atherosclerosis is a chronic inflammatory disease that is initiated by the
      retention and accumulation of low-density lipoprotein in the artery, leading to
      maladaptive response of cells from the immune system and vessel wall. Strong
      evidence implicates indoleamine 2,3-dioxygenase (IDO), the first and rate
      limiting enzyme of the kynurenine pathway of tryptophan (Trp) degradation, with
      immune regulation and anti-inflammatory mechanisms in different diseases.
      However, the role of IDO and the endogenous degradation of Trp have never been
      directly examined in atherosclerosis development. We used the IDO inhibitor 1
      methyl-Trp (1-MT) to determine the role of IDO-mediated Trp metabolism in
      vascular inflammation and atherosclerosis. METHODS AND RESULTS: Apoe(-/-) mice
      were treated with 1-MT in drinking water for 8 weeks. Systemic IDO inhibition led
      to a significant increase in atherosclerotic lesions that were ~58 and 54% larger
      in the aortic arch and root, respectively. 1-MT treatment enhanced vascular
      inflammation, up-regulated VCAM-1 and CCL2, and increased CD68 macrophage
      accumulation into the plaque. Notably, the rise in VCAM-1 expression was not
      limited to the plaque but also found in smooth muscle cells (SMCs) of the tunica
      media. Furthermore, we found that IDO-dependent Trp metabolism by SMCs regulates
      VCAM-1 expression, and that 1-MT-induced acceleration of atherosclerosis and
      vascular inflammation can be reversed by exogenous administration of the Trp
      metabolite 3-hydroxyanthranilic acid (3-HAA). CONCLUSION: IDO-mediated Trp
      metabolism regulates vascular inflammation and plaque formation in
      hypercholesterolaemic Apoe(-/-) mice. Our data establish that this pathway plays
      a major role in the pathological process of atherogenesis.

PMID- 25750191
TI  - Regulation of leucocyte homeostasis in the circulation.
AB  - The functions of blood cells extend well beyond the immune functions of
      leucocytes or the respiratory and hemostatic functions of erythrocytes and
      platelets. Seen as a whole, the bloodstream is in charge of nurturing and
      protecting all organs by carrying a mixture of cell populations in transit from
      one organ to another. To optimize these functions, evolution has provided blood
      and the vascular system that carries it with various mechanisms that ensure the
      appropriate influx and egress of cells into and from the circulation where and
      when needed. How this homeostatic control of blood is achieved has been the
      object of study for over a century, and although the major mechanisms that govern
      it are now fairly well understood, several new concepts and mediators have
      recently emerged that emphasize the dynamism of this liquid tissue. Here we
      review old and new concepts that relate to the maintenance and regulation of
      leucocyte homeostasis in blood and briefly discuss the mechanisms for platelets
      and red blood cells. 

PMID- 25750194
TI  - Extensive myocardial calcification after acute myocarditis.

PMID- 25750195
TI  - E-learning in cardiovascular imaging: another step towards a structured
      educational approach.

PMID- 25750193
TI  - Left atrial strain is a powerful predictor of atrial fibrillation recurrence
      after catheter ablation: study of a heterogeneous population with sinus rhythm or
      atrial fibrillation.
AB  - AIMS: Accumulating data show the efficacy of catheter ablation (CA) for atrial
      fibrillation (AF); however, postoperative recurrence is not uncommon. The aim of
      this study was to identify predictors of AF recurrence in patients undergoing CA.
      METHODS AND RESULTS: We studied 100 patients with symptomatic paroxysmal (68) or
      persistent (32) AF who underwent CA preceded by transthoracic echocardiographic
      examination. Of these, 50 had sinus rhythm during echocardiography (Group NSR)
      and 50 had AF rhythm (Group AF). The left atrial (LA) strain was measured by two
      dimensional speckle tracking echocardiography. Echocardiographic parameters were
      compared between the patients with AF recurrence and no recurrence. During 12
      months of follow-up, 26 of 100 patients (11 in Group NSR and 15 in Group AF) had
      AF recurrence; these patients had significantly longer AF duration, a lower LA
      global strain (LA-GS), lower LA lateral total strain (LA-LS), and larger maximum
      LA volume index (LAVImax) than those who maintained sinus rhythm. Multivariate
      logistic regression identified basal LA-LS and LAVImax as independent predictors
      of AF recurrence. Furthermore, receiver operating characteristic analyses
      revealed that basal LA-LS was the most useful parameter for predicting AF
      recurrence [area under the curve (AUC): 0.84 vs. 0.74 in LAVImax]. Subanalyses
      showed that LAVImax was another independent predictor of AF recurrence in Group
      AF, but not in Group NSR, while basal LA-LS was a significant predictor in both
      groups. CONCLUSION: LA myocardial function assessed by basal LA-LS could predict
      AF recurrence after CA. Notably, such an assessment could be applicable even
      during AF rhythm, suggesting its convenience in the clinical setting without
      defibrillation before analysis.

PMID- 25750196
TI  - Bronchogenic cyst compressing the pulmonary artery and the left atrium.

PMID- 25750197
TI  - Malcoaptation of the pulmonary valve diagnosed using transthoracic 3D
      echocardiography.

PMID- 25750198
TI  - Normal left-atrial structure and function despite concentric left-ventricular
      remodelling in a cohort of patients with Anderson-Fabry disease.
AB  - AIMS: Anderson-Fabry Disease (AFD) is an important cause of cardiomyopathy
      characterized by concentric left-ventricular hypertrophy (LVH). We evaluated the
      extent of left-atrial (LA) structural and functional remodelling in this group of
      patients given that LA remodelling is a marker of adverse outcomes in the
      presence of LVH. METHODS AND RESULTS: Clinical profiles were obtained and cardiac
      MRI was performed in cohorts of patients with AFD (n = 31), healthy controls (n =
      23), and a positive control cohort with known concentric remodelling and LVH
      (CR/H, n = 21). Of patients with AFD, 58% were on enzyme-replacement therapy
      (ERT), 84% were on renin-angiotensin system antagonism, and 65% were on statins.
      Despite a similar increase in LV mass index in the AFD when compared with the
      CR/H cohort, mean LA volumes for the AFD group were similar to those seen in the
      healthy control group. Following from this, we observed that the percentage
      contribution to LV stroke volume due to elastic/passive and active LA emptying
      was similar in the AFD and healthy control groups, while passive emptying was
      significantly lower in the CR/H group. The consequences of LVH in the AFD cohort
      were manifested in atrioventricular uncoupling, whereby the extent of
      elastic/passive and active LA emptying was not a function of the extent of
      longitudinal movement of the mitral annular plane, as it was in healthy control
      subjects. CONCLUSION: Left-atrial structure and function were relatively normal
      in our cohort of patients with AFD, who were also judiciously treated with a
      contemporary strategy that includes renin-angiotensin system antagonism, statins,
      and ERT.

PMID- 25750199
TI  - 3-D Transoesophageal echocardiography for guiding percutaneous stenting of
      pulmonary vein stenosis.

PMID- 25750200
TI  - Chronic giant hydatid cyst fistulized to the left ventricle: long-term survival
      without surgery.

PMID- 25750201
TI  - Left ventricular diastolic function, assessed by echocardiography and tissue
      Doppler imaging, is a strong predictor of cardiovascular events, superior to
      global left ventricular longitudinal strain, in patients with type 2 diabetes.
AB  - AIMS: The aim of the study was to determine whether left ventricular systolic
      function, in terms of global left ventricular longitudinal strain (GLS), and
      diastolic function, expressed as the ratio between early diastolic transmitral
      flow and mitral annular motion velocities (E/e'), can predict cardiovascular
      events in patients with diabetes mellitus type 2. METHODS AND RESULTS: We
      prospectively investigated 406 consecutive patients, aged 55-65 years, with
      diabetes mellitus, who participated in the CARDIPP study. Echocardiography, pulse
      pressure (pp), and glycosylated haemoglobin (HbA1c) were analysed. Twelve cases
      of myocardial infarction and seven cases of stroke were identified during the
      follow-up period of 67 +/- 17 months. Univariate Cox regression analysis showed
      that E/e' was a strong predictor of cardiovascular events (hazards ratio 1.12;
      95% confidence interval 1.06-1.18, P < 0.001). E/e' was prospectively associated
      with cardiovascular events independent of age, sex, GLS, left ventricular
      ejection fraction (LVEF), pp, and HbA1c in multivariate analysis. Receiver
      operating characteristic curves showed that E/e' and HbA1c were the strongest
      predictors for cardiovascular events, both having an area under the curve (AUC)
      of 0.71 followed by LVEF with an AUC of 0.65 and GLS of 0.61. In a Kaplan-Meyer
      analysis, the cumulative probability of an event during the follow-up period was
      8.6% for patients with an E/e' ratio >15 compared with 2.6% for patients with
      E/e' <=15, P = 0.011. CONCLUSION: In middle-aged patients with type 2 diabetes,
      E/e' is a strong predictor of myocardial infarction and stroke, comparable with
      HbA1c and superior to GLS and LVEF.

PMID- 25750202
TI  - Giant and electrically silent right atrium.

PMID- 25750203
TI  - Novel missense mutation in WNT6 in 100 couples with unexplained recurrent
      miscarriage.
AB  - STUDY QUESTION: Do mutations and/or polymorphisms in coding sequences in Wingless
      Type MMTV Integration Site Family, Member 6 (WNT6) play a role in unexplained
      recurrent miscarriage (unexplained RM) in Chinese couples? SUMMARY ANSWER: We
      found four mutations in the coding sequences of WNT6 which appear to exist in a
      small proportion of Chinese women with unexplained RM. WHAT IS KNOWN ALREADY:
      WNT6 has been proved to be essential for stromal cell proliferation during
      decidualization in mice, but in humans WNT6 has not been studied in recurrent
      miscarriage populations. STUDY DESIGN, SIZE, DURATION: For this study, 100
      couples with unexplained RM (at least three or more unexplained spontaneous
      miscarriages), and 100 ethnically matched fertile couples (at least one live
      birth and no history of pregnancy pathologies) were recruited. All the
      participants were chosen over a 7-year period from the National Research Center
      for Assisted Reproductive Technology and Reproductive Genetics at Shandong
      University, Jinan, China. PARTICIPANTS/MATERIALS, SETTING, METHODS: Patients were
      recruited following extensive clinical studies. Genomic DNA was isolated from
      peripheral blood. Mutation analysis in the coding regions of WNT6 was performed
      by PCR amplification and DNA sequences testing in all participants. Functional
      effects of missense variants were predicted using Polyphen-2 and sorting
      intolerant from tolerant (SIFT). MAIN RESULTS AND THE ROLE OF CHANCE: Four rare
      novel mutations, including one missense mutation, were found in intron 1, exon 3
      and the 3' untranslated region of WNT6 in four women with unexplained RM. Gene
      software predictions showed that the missense mutation in exon 3 could alter the
      function of WNT6. No mutations or polymorphisms were detected in the male
      partners of the unexplained RM patients or in the fertile controls. To further
      validate the findings, we continued to screen this missense mutation site in
      another 100 peripheral blood samples of normal fertile females, and there was
      still no positive result. LIMITATIONS, REASONS FOR CAUTION: There is no direct
      evidence to validate whether these novel mutations discovered in the present
      research are related to unexplained RM. Further studies are warranted to
      investigate the role of WNT6 in unexplained RM, including larger studies in an
      independent group. WIDER IMPLICATIONS OF THE FINDINGS: These results provide
      evidence to suggest the importance of WNT6 in reproductive failure and may
      support the hypothesis that WNT6 is essential for stromal cell proliferation
      during decidualization. STUDY FUNDING/COMPETING INTERESTS: This work was
      supported by Science and Technology Development Planning of Shandong
      (2013GGE27001), the National Natural Science Foundation of China (81300459), the
      Science Projection of Bureau of Public Health in Weifang (2012044) and the
      Science Research Foundation Item of No-earnings Health Vocation. The authors have
      no competing interests to declare.

PMID- 25750205
TI  - Observation shows, intervention teaches - Claude Bernard.

PMID- 25750204
TI  - Induction of post-menstrual regeneration by ovarian steroid withdrawal in the
      functionalis of xenografted human endometrium.
AB  - STUDY QUESTION: Does the endometrial functionalis have the potential to undergo
      self-renewal after menstruation and how is this process controlled by ovarian
      steroids? SUMMARY ANSWER: Endometrial xenografts subjected to withdrawal of
      estradiol and progesterone shrink but also show signs of proliferation and tissue
      repair; new estradiol supply prevents atrophy but is not sufficient to increase
      graft volume. WHAT IS KNOWN ALREADY: Menstruation, i.e. cyclic proteolysis of the
      extracellular matrix of endometrial functionalis, is induced by a fall in
      estrogen and progesterone concentration and is followed by tissue regeneration.
      However, there is debate about whether regenerating cells must originate from the
      basalis or from stem cells and whether new estrogen supply is required for the
      early repair concomitant with menstruation. STUDY DESIGN, SIZE, DURATION:
      Fragments from human endometrial functionalis (from 24 hysterectomy specimens)
      were xenografted in ovariectomized SCID mice and submitted to a 4-day estradiol
      and progesterone withdrawal (to mimic menstruation) followed by re-exposure to
      estradiol (to mimic the proliferative phase). We measured signs of proliferation
      and changes in graft volume. PARTICIPANTS/MATERIALS, SETTING, METHODS:
      Endometrium was collected from spontaneously cycling women. Cell proliferation
      was examined by immunolabeling Ki-67, cyclin D1 and phosphorylated-histone H3.
      Xenograft volume was measured by magnetic resonance imaging. Xenograft
      histomorphometry was performed to determine how the different tissue compartments
      contributed to volume change. MAIN RESULTS AND THE ROLE OF CHANCE: Hormone
      withdrawal induced a rapid decrease in graft volume mainly attributable to stroma
      condensation and breakdown, concomitant with an increase of proliferation
      markers. Reinsertion of estradiol pellets after induced menstruation blocked
      volume decrease and stimulated epithelial and stromal growth, but, surprisingly,
      did not induce graft enlargement. Reinsertion of both estradiol and progesterone
      pellets blocked apoptosis. LIMITATIONS, REASONS FOR CAUTION: Mechanisms of
      endometrial remodeling are different in women and mice and the contribution of
      circulating inflammatory cells in both species remains to be clarified. Moreover,
      during human menstruation, endometrial fragments resulting from tissue
      proteolysis can be expelled by the menstrual flow, unlike in this model. WIDER
      IMPLICATIONS OF THE FINDINGS: Menstruation is a multifocal event within the
      functionalis. This is the first evidence that endometrial fragments that are not
      shed after menstrual tissue breakdown can support endometrial regeneration.
      Endometriosis is commonly thought to result from the retrograde migration of
      menstrual fragments of the degraded functionalis into the peritoneal cavity. Our
      study supports their potential to regenerate as ectopic endometrium. STUDY
      FUNDING/COMPETING INTERESTS: This work was supported by the Fonds de la Recherche
      Scientifique Medicale, Concerted Research Actions, Communaute Francaise de
      Belgique, Region wallonne, Region bruxelloise and Loterie nationale. P.H. and
      B.F.J. are research associates of the Belgian Fonds de la Recherche Scientifique
      (F.R.S.-F.N.R.S.). E.M. is Associate Editor at Human Reproduction. There is no
      conflict of interest to declare.

PMID- 25750206
TI  - Reply: time-lapse in the IVF lab: how should we assess potential benefit?

PMID- 25750207
TI  - Time-lapse in the IVF lab: how should we assess potential benefit?

PMID- 25750209
TI  - Risks of conservative management in women with ovarian endometriomas undergoing
      IVF.
AB  - BACKGROUND: Classical surgical management of endometriotic ovarian cysts using
      the laparoscopic stripping technique has been recently questioned because of the
      surgical-related injury to the ovarian reserve. Accordingly, available guidelines
      suggest that endometriomas with a mean diameter below 4 cm should not be
      systematically removed before IVF procedures. However, conservative management
      may have some potential drawbacks and risks. The presence of the endometrioma may
      theoretically interfere with ovarian responsiveness to hyperstimulation and
      oocyte competence, the retrieval of the oocytes may be more difficult and risky,
      the disease may progress during the procedure, pregnancy outcome may be affected
      and there is the risk of missing occult malignancies with cancer development
      later in life. In the present review, we aimed at assessing whether these risks
      do exist and, if so, at estimating their clinical relevance. METHODS: We searched
      PubMed for articles published in the English language between January 1990 and
      August 2014 that reported on endometriomas and assisted reproductive techniques.
      Special care was given to studies reporting data purporting to distinguish the
      effects of ovarian endometriomas per se from those consequent to surgery for
      endometriosis or from endometriosis in general. RESULTS: Based on the evidence
      reviewed in the present study, it can be concluded that conservative management
      may actually expose women to four of the following theoretical risks, i.e.
      infection of the endometriomas, follicular fluid contamination with the
      endometrioma content, higher risk of pregnancy complications and cancer
      development later in life. The first three conditions do not justify surgery
      because these events are uncommon and the number of women needed to be treated
      would be exceedingly high and would not justify the costs and risks of the
      intervention. Albeit also very rare, the possibility of developing ovarian cancer
      later in life is more troublesome because it is a life-threatening condition.
      However, this alarmism is supported by only one cohort study and this risk can be
      effectively prevented by postponing surgery until after the IVF programme is
      concluded or when women have definitely satisfied their reproductive wishes.
      CONCLUSION: The available evidence on the risks of conservative management does
      not support systematic surgery before IVF in women with small ovarian
      endometriomas.

PMID- 25750208
TI  - Human primordial germ cell commitment in vitro associates with a unique PRDM14
      expression profile.
AB  - Primordial germ cells (PGCs) develop only into sperm and oocytes in vivo. The
      molecular mechanisms underlying human PGC specification are poorly understood due
      to inaccessibility of cell materials and lack of in vitro models for tracking the
      earliest stages of germ cell development. Here, we describe a defined and
      stepwise differentiation system for inducing pre-migratory PGC-like cells
      (PGCLCs) from human pluripotent stem cells (PSCs). In response to cytokines, PSCs
      differentiate first into a heterogeneous mesoderm-like cell population and then
      into PGCLCs, which exhibit minimal PRDM14 expression. PGC specification in humans
      is similar to the murine process, with the sequential activation of mesodermal
      and PGC genes, and the suppression of neural induction and of de novo DNA
      methylation, suggesting that human PGC formation is induced via epigenesis, the
      process of germ cell specification via inductive signals from surrounding somatic
      cells. This study demonstrates that PGC commitment in humans shares key features
      with that of the mouse, but also highlights key differences, including
      transcriptional regulation during the early stage of human PGC development (3-6
      weeks). A more comprehensive understanding of human germ cell development may
      lead to methodology for successfully generating PSC-derived gametes for
      reproductive medicine.

PMID- 25750211
TI  - Outcome with peripheral versus central cannulation in acute Type A dissection ?.
AB  - OBJECTIVES: Acute aortic dissection type A (AADA) is still an emergency operation
      with high morbidity and mortality. In this acute situation quick cannulation to
      the heart-lung machine and systemic cooling is often life-saving. However, the
      often easy access to the femoral vessels for cannulation leads to an arterial
      backflow in the descending aorta with the likelihood of plaque rupture and
      cerebral embolism. We analysed the outcome after initial femoral versus central
      cannulation for AADA. METHODS: All patients with acute aortic dissection type A
      operated between January 2003 and December 2012 were evaluated for the type of
      arterial cannulation (femoral vs central) for initial bypass. Demographic data
      and outcome parameters were accessed. No patient was excluded. RESULTS: One
      hundred and seventy-seven patients were operated on with acute type A dissection
      in the last 10 years; 94 (53.1%) were initially cannulated in the central aortic
      vessels and 83 (46.9%) in the femoral artery. The patients were comparable with
      regard to age (61.1 +/- 14.9 vs 62.2 +/- 15.0 years, P = 0.607), gender (male, 62
      vs 69%, P = 0.348), EuroSCORE (11.5 +/- 4.0 vs 12.8 +/- 4.3, P = 0.057) and
      previous sternotomy (17% in both groups). Bypass (243 +/- 105 vs 233 +/- 83 min,
      P = 0.471), cross-clamp (160 +/- 86 vs 150 +/- 66 min, P = 0.381) and circulatory
      arrest times (47.8 +/- 24.7 vs 42.5 +/- 21.7 min, P = 0.130) were similar as were
      lowest temperatures (17.7 +/- 1.8 vs 17.6 +/- 1.3, P = 0.652). Postoperative
      cerebral infarction and 30-day mortality were comparable between the cannulation
      groups (13 vs 9%, P = 0.449 and 20 vs 17%, P = 0.699, central vs peripheral
      cannulation). Only postoperative need for dialysis was borderline significantly
      higher in the femoral cannulation group (28 vs 40%, P = 0.073). CONCLUSIONS: This
      single-centre study with 177 patients could show that an acute aortic dissection
      type A can be operated on with central and peripheral cannulation with similar
      results. Risk for early mortality was driven by the preoperative clinical and
      haemodynamic status before operation rather than the cannulation technique.

PMID- 25750210
TI  - A streptococcal lipid toxin induces membrane permeabilization and pyroptosis
      leading to fetal injury.
AB  - Group B streptococci (GBS) are Gram-positive bacteria that cause infections in
      utero and in newborns. We recently showed that the GBS pigment is hemolytic and
      increased pigment production promotes bacterial penetration of human placenta.
      However, mechanisms utilized by the hemolytic pigment to induce host cell lysis
      and the consequence on fetal injury are not known. Here, we show that the GBS
      pigment induces membrane permeability in artificial lipid bilayers and host
      cells. Membrane defects induced by the GBS pigment trigger K(+) efflux leading to
      osmotic lysis of red blood cells or pyroptosis in human macrophages. Macrophages
      lacking the NLRP3 inflammasome recovered from pigment-induced cell damage. In a
      murine model of in utero infection, hyperpigmented GBS strains induced fetal
      injury in both an NLRP3 inflammasome-dependent and NLRP3 inflammasome-independent
      manner. These results demonstrate that the dual mechanism of action of the
      bacterial pigment/lipid toxin leading to hemolysis or pyroptosis exacerbates
      fetal injury and suggest that preventing both activities of the hemolytic lipid
      is likely critical to reduce GBS fetal injury and preterm birth.

PMID- 25750212
TI  - Gender difference in adrenal sensitivity to ACTH is abolished in type 2 diabetes.
AB  - OBJECTIVE: Dysfunction of the hypothalamus-pituitary-adrenal (HPA) axis has been
      implicated in type 2 diabetes (T2D). The aim of this study was to investigate the
      impact of T2D and gender on the HPA axis. METHODS: Synthetic ACTH (1 MUg) was
      administered to 21 subjects with T2D (age 62 (54-70) years, 11 men/ten women,
      HbA1c 49+/-2 mmol/mol, treated with diet or oral antidiabetic drugs) and 38
      controls (age 58 (41-67) years, 20 men/18 women). Fasting basal B-glucose, serum
      cortisol, insulin, IGF1 and IGFBP1 concentrations were measured, and sampling for
      all but IGF1 was repeated 30, 60, and 90 min after ACTH injection. Patients took
      0.25 mg dexamethasone at 2200-2300 h and returned the next morning for the
      measurement of serum cortisol concentration. DESIGN: Cross-sectional study.
      RESULTS: Patients with T2D had similar fasting serum cortisol, IGF1 and IGFBP1
      concentrations; however, serum cortisol concentration after administration of
      dexamethasone did not differ between the groups. Healthy women exhibited higher
      peak cortisol levels compared with healthy men (675+/-26 vs 582+/-21 nmol/l,
      P=0.014), while the peak levels were equally high in men and women with T2D,
      resulting in a higher peak level in men with T2D compared with healthy men (691+/
      42 vs 582+/-21 nmol/l, P=0.024). Serum cortisol concentration after
      administration of dexamethasone did not differ between the groups, nor did IGF1
      and IGFBP1. NOVELTY OF THE FINDINGS: Some studies have previously indicated
      disturbed regulation of the hypothalamus-pituitary-adrenal (HPA) axis in subjects
      with type 2 diabetes (T2D); however, much remains unknown in this area. To the
      best of our knowledge, this is the first study to show that the gender difference
      in the adrenal response to ACTH (with greater reactivity in women) is abolished
      in T2D. While the clinical implications cannot be determined by this paper, it is
      known that gender differences exist in the pathogenesis and complications of T2D.
      Thus, our findings suggest that further research into gender differences in the
      HPA axis is warranted. CONCLUSIONS: Gender differences in adrenal response to
      ACTH were abolished in T2D. Men with T2D had a higher peak cortisol compared with
      controls. Further studies are needed to elucidate the clinical implications.

PMID- 25750215
TI  - Combined analysis of unipolar and bipolar voltage mapping identifies recurrences
      after unmappable scar-related ventricular tachycardia ablation.
AB  - AIMS: Scars causing ventricular tachycardia can extend deep to and beyond bipolar
      low-voltage areas (LVAs) and they may be a reason for endocardial ablation
      failure. Analysis of endocardial unipolar voltage maps has been used to detect
      scar transmurality and epicardial scar. We hypothesized that endocardial unipolar
      LVA around the overlying bipolar LVA may predict endocardial ablation recurrence
      in patients with structural heart disease undergoing substrate modification.
      METHODS AND RESULTS: Twenty consecutive patients with structural heart disease
      (11 ischaemic and 9 non-ischaemic cardiomyopathy) and undergoing substrate
      modification due to unmappable ventricular tachycardia (VT) (18 males, 51 +/- 11
      age, LVEF: 36 +/- 7%) were retrospectively reviewed. Bipolar LVA defined as <1.5
      mV and unipolar LVA defined as <8.3 mV, respectively, on electro-anatomic mapping
      system. Peripheral unipolar LVA (pUni-LVA) surrounding bipolar LVA was measured
      and compared patients with and without VT recurrence at 6-month follow-up period.
      : Mean unipolar voltage and mean bipolar voltage was 6.26 +/- 4.99 and 1.90 +/-
      2.30 mV, respectively. Bipolar voltage and unipolar voltage in corresponding
      points were correlated (r = 0.652, P = 0.0001). In all patients, unipolar LVAs
      were larger than the bipolar LVAs. Bipolar LVA (91.1 +/- 93.5 vs. 87.5 +/- 47.5
      cm(2), P = 0.91) and unipolar LVA (148.1 +/- 96.3 vs. 104.7 +/- 44.2 cm(2), P =
      0.21) were similar in patients with and without VT recurrence, respectively.
      Peripheral unipolar LVA was significantly larger in patients with VT recurrence
      than without (57.0 +/- 40.4 vs. 17.2 +/- 12.9 cm(2), P = 0.01). CONCLUSION: In
      patients with structural heart disease and unmappable VT, pUni-LVA surrounding
      bipolar scar predicts recurrence of VT ablation. The results of this pilot study
      highlight the importance of intramural/epicardial substrate on endocardial VT
      ablation outcome.

PMID- 25750213
TI  - Neospora caninum Recruits Host Cell Structures to Its Parasitophorous Vacuole and
      Salvages Lipids from Organelles.
AB  - Toxoplasma gondii and Neospora caninum, which cause the diseases toxoplasmosis
      and neosporosis, respectively, are two closely related apicomplexan parasites.
      They have similar heteroxenous life cycles and conserved genomes and share many
      metabolic features. Despite these similarities, T. gondii and N. caninum differ
      in their transmission strategies and zoonotic potential. Comparative analyses of
      the two parasites are important to identify the unique biological features that
      underlie the basis of host preference and pathogenicity. T. gondii and N. caninum
      are obligate intravacuolar parasites; in contrast to T. gondii, events that occur
      during N. caninum infection remain largely uncharacterized. We examined the
      capability of N. caninum (Liverpool isolate) to interact with host organelles and
      scavenge nutrients in comparison to that of T. gondii (RH strain). N. caninum
      reorganizes the host microtubular cytoskeleton and attracts endoplasmic reticulum
      (ER), mitochondria, lysosomes, multivesicular bodies, and Golgi vesicles to its
      vacuole though with some notable differences from T. gondii. For example, the
      host ER gathers around the N. caninum parasitophorous vacuole (PV) but does not
      physically associate with the vacuolar membrane; the host Golgi apparatus
      surrounds the N. caninum PV but does not fragment into ministacks. N. caninum
      relies on plasma lipoproteins and scavenges cholesterol from NPC1-containing
      endocytic organelles. This parasite salvages sphingolipids from host Golgi Rab14
      vesicles that it sequesters into its vacuole. Our data highlight a remarkable
      degree of conservation in the intracellular infection program of N. caninum and
      T. gondii. The minor differences between the two parasites related to the
      recruitment and rearrangement of host organelles around their vacuoles likely
      reflect divergent evolutionary paths. 

PMID- 25750216
TI  - Transseptal puncture from the jugular vein and balloon cryoablation for atrial
      fibrillation in a patient with azygos continuation of an interrupted inferior
      vena cava.
AB  - AIMS: Inferior vena cava (IVC) interruption is a rare anatomic variant where the
      azygos vein (AV) drains the blood from the IVC to the upper part of the right
      atrium via the superior vena cava. Here, we report balloon cryoablation of the
      pulmonary veins (PVs) via superior access in a patient with atrial fibrillation.
      METHODS AND RESULTS: After the first failed ablation attempt due to IVC
      interruption, balloon cryoablation with a 28-mm Arctic Front Advance cryoballoon
      (Medtronic CryoCath LP, Quebec, Canada) via superior access was performed; it
      requires only a single transseptal puncture (TP), and the patient had optimal PV
      anatomy. Deflectable electrodes were inserted into the right ventricle and
      coronary sinus from the right femoral vein. The right internal jugular vein was
      accessed using an SL0 transseptal sheath and BRK needle. The TP was performed
      under transoesophageal echocardiographic guidance with a Safe Sept wire because
      the septum was stiff. All PVs were engaged: the left using an ablation catheter
      before balloon insertion and the inferior following a 'push-up' technique because
      of a leak above the veins. Cryothermal energy was delivered after checking for
      occlusion. The procedure lasted 210 min, fluoroscopy time was 78 min, and air
      kerma dose was 194 mGy. During the 6-month follow-up, no episodes of atrial
      fibrillation were detected on several Holter recordings. CONCLUSIONS: Successful
      PV isolation in patients with AV continuation of an interrupted IVC can be safely
      performed using superior access with balloon cryoablation, after several
      modifications of standard equipment.

PMID- 25750214
TI  - Analysis of the Candida albicans Phosphoproteome.
AB  - Candida albicans is an important human fungal pathogen in both immunocompetent
      and immunocompromised individuals. C. albicans regulation has been studied in
      many contexts, including morphological transitions, mating competence, biofilm
      formation, stress resistance, and cell wall synthesis. Analysis of kinase- and
      phosphatase-deficient mutants has made it clear that protein phosphorylation
      plays an important role in the regulation of these pathways. In this study, to
      further our understanding of phosphorylation in C. albicans regulation, we
      performed a deep analysis of the phosphoproteome in C. albicans. We identified
      19,590 unique peptides that corresponded to 15,906 unique phosphosites on 2,896
      proteins. The ratios of serine, threonine, and tyrosine phosphosites were 80.01%,
      18.11%, and 1.81%, respectively. The majority of proteins (2,111) contained at
      least two detected phosphorylation sites. Consistent with findings in other
      fungi, cytoskeletal proteins were among the most highly phosphorylated proteins,
      and there were differences in Gene Ontology (GO) terms for proteins with serine
      and threonine versus tyrosine phosphorylation sites. This large-scale analysis
      identified phosphosites in protein components of Mediator, an important
      transcriptional coregulatory protein complex. A targeted analysis of the
      phosphosites in Mediator complex proteins confirmed the large-scale studies, and
      further in vitro assays identified a subset of these phosphorylations that were
      catalyzed by Cdk8 (Ssn3), a kinase within the Mediator complex. These data
      represent the deepest single analysis of a fungal phosphoproteome and lay the
      groundwork for future analyses of the C. albicans phosphoproteome and specific
      phosphoproteins. 

PMID- 25750217
TI  - SLE or hypothyroidism: who can triumph in cardiac tamponade?
AB  - A 36-year-old Hispanic woman with a history of systemic lupus erythaematosus
      (SLE) in remission presented with progressive dyspnoea, bilateral leg swelling
      and increasing fatigue with rapid weight gain over the past few months. Her
      physical examination showed mildly tender thyromegaly and pericardial rub.
      Investigations showed new onset marked hypothyroidism as well as an active lupus
      serology with echocardiogram confirming severe pericardial effusion and a
      tamponade phenomenon. Urgent pericardiocentesis relieved her acute symptoms, and
      prompt treatment with thyroxine replacement and immunosuppression for lupus
      disease was initiated. Pericardial fluid analysis remained negative for any
      malignancy and/or infection/s. The patient had a gradual and consistent
      improvement with this treatment. She was discharged and appeared to be clinically
      stable at subsequent follow-up visits. However, the case remained a diagnostic
      dilemma over whether the tamponade was being driven by hypothyroidism versus
      lupus, leaving us with an opportunity to explore further. 

PMID- 25750218
TI  - Endocarditis of the native aortic valve caused by Lactobacillus jensenii.
AB  - Lactobacilli are Gram-positive anaerobic rods or coccobacilli, commonly found as
      commensals in human mucosa. Rarely, they can cause serious infections such as
      infective endocarditis (IE), and the most frequently implicated species causing
      serious infections are L. casei and L. rhamnosus. IE caused by Lactobacillus
      jensenii is very rare, with only six reported cases so far, to the best of our
      knowledge. We present a case of native aortic valve endocarditis caused by L.
      jensenii, complicated by root abscess and complete heart block, and requiring
      emergent surgical intervention. 

PMID- 25750219
TI  - Spontaneous iliopsoas muscle haematoma as a complication of anticoagulation in
      acute cerebral venous thrombosis: to stop or not to stop (the anticoagulation)?
AB  - Spontaneous iliopsoas muscle haematoma is an infrequent complication of
      anticoagulation, potentially causing neurological dysfunction through compression
      of the femoral nerve or lumbar plexus. The authors report the case of a puerperal
      woman admitted for an extensive cerebral venous thrombosis. Anticoagulation was
      started, with clinical improvement. The patient later reported low back pain
      irradiating to the right thigh and developed neurological impairment consistent
      with lumbar plexus dysfunction. A pelvic CT scan revealed a right iliopsoas
      muscle haematoma. Considering the risk of anticoagulation suspension, a
      conservative approach was chosen, with maintenance of anticoagulation. Clinical
      and functional improvement occurred, with mild right hip and knee flexion paresis
      as sequelae. Anticoagulation complications are challenging, especially when
      interruption of anticoagulation may threaten vital and functional outcomes.
      Therefore, a careful evaluation is essential, since no clinical guidelines are
      available. In this case, continuing anticoagulation provided a good functional
      outcome. 

PMID- 25750220
TI  - Zinner syndrome: an uncommon cause of painful ejaculation.
AB  - Zinner syndrome refers to the triad of ipsilateral renal agenesis, seminal
      vesicle cysts and ejaculatory duct obstruction. Ipsilateral renal agenesis may be
      associated with seminal vesicle cysts in 70% of cases, but a remnant ureteral bud
      has been shown to coexist in only 27% of these cases. While some patients may
      remain asymptomatic and are discovered incidentally, others present with symptoms
      related to seminal vesicle cysts or ejaculatory duct obstruction: voiding or
      ejaculatory difficulty or pain. The diagnosis is made with imaging findings, and
      differentiation from other pelvic cysts requires a multimodality approach. In
      this report, we present typical imaging findings of a patient who presented with
      painful ejaculation where there was a congenital seminal vesicle cyst with
      ipsilateral renal agenesis associated with a remnant ureteral bud draining into
      the seminal vesicle cyst and also associated with a cyst of the prostatic
      utricle. We discuss the relevant embryological basis for this unusual combination
      of findings. 

PMID- 25750221
TI  - Massive surgical emphysema secondary to iatrogenic tracheal laceration.
AB  - A 78-year-old woman was admitted for a revision total hip replacement following a
      failed dynamic hip screw placed emergently 4 months earlier. Anaesthetic
      management consisted of general anaesthesia with endotracheal intubation and
      femoral nerve block. The patient's perioperative course was unremarkable except
      for a promptly recognised and corrected oesophageal intubation and a short period
      of breathing against a closed adjustable pressure limiting valve. In recovery,
      following a period of hypotension resistant to fluid therapy, she suddenly
      desaturated, developed severe facial and upper thoracic subcutaneous emphysema
      and type 2 respiratory failure. She was diagnosed with bilateral pneumothoraces,
      pneumomediastinum, pneumopericardium and surgical emphysema. This was treated
      emergently with supplemental oxygen and bilateral chest drains. A CT scan
      demonstrated a tracheal laceration, which was managed conservatively in the
      critical care unit. The patient had a tracheostomy on day 5 to treat an on-going
      air leak and later made a full recovery.

PMID- 25750222
TI  - Gross haematuria associated with penetration of an inferior vena cava filter into
      the right renal collecting system.
AB  - Inferior vena cava (IVC) filters are a viable alternative for patients with
      venous thromboembolic disease for whom standard anticoagulation therapy is
      contraindicated. Rare complications associated with their use, however, include
      misplacement and IVC penetration. We report a case of a 63-year-old woman who
      developed gross haematuria following IVC filter penetration into both the right
      renal collecting system and renal pelvis, for which open caval removal and
      reconstruction was required. This is an unusual case of IVC filter penetration
      causing symptomatic haematuria and requiring surgical intervention. 

PMID- 25750223
TI  - Sclerosing lipogranuloma of the eyelid: unusual complication following nasal
      packing in endoscopic sinus surgery.
AB  - An eyelid or orbital lipogranuloma can occur following nasal packing with liquid
      paraffin, petroleum jelly or an antibiotic-based cream. It usually presents a few
      weeks or months after the initial procedure. We present a report of three such
      cases of sclerosing lipogranuloma involving the eyelid, which occurred following
      a sinonasal surgery where nasal packing using petroleum jelly was performed. The
      typical clinical course and the classical histopathological features are
      highlighted. All cases were diagnosed by histopathological examination as
      sclerosing lipogranuloma. Complete surgical removal resulted in complete
      resolution on 1 month follow-up. The diagnosis is based on a high degree of
      suspicion following a detailed history of prior use of lipid-based products for
      nasal packing following endonasal surgery. Histopathology is diagnostic. Surgical
      excision is the treatment of choice, however, due to its infiltrative nature, it
      may be difficult to obtain a complete cure.

PMID- 25750224
TI  - Hyaline globules in fine-needle aspiration smears of salivary gland neoplasms.
AB  - Most salivary gland neoplasms can be accurately diagnosed on fine-needle
      aspiration cytology. Few cases present with overlapping cytomorphological
      features, so accurate distinction in these cases may be difficult. We describe a
      case of pleomorphic adenoma that had a close resemblance to adenoid cystic
      carcinoma on smears due to presence of numerous hyaline globules and bare nuclei.
      Careful analysis of cellular details along with corroborative clinical evidence
      clinched the correct diagnosis. This article discusses cytological features of
      salivary gland tumours in which hyaline globules can be seen on smears. 

PMID- 25750225
TI  - T-cell primary leptomeningeal lymphoma in cerebellopontine angle.
AB  - Primary meningeal lymphomas are very rare and those derived from T cells are even
      more infrequent (less than 5% of primary central nervous system lymphomas).
      Cerebellopontine angle involvement in the primary T-cell lymphoma is exceptional.
      Clinical presentation depends on the type of lesions, and histological diagnosis
      is needed. We present a rare case of a 50-year-old woman who presented with
      clinical cerebellar syndrome with posterior opsoclonus-myoclonus syndrome.
      Necropsy evaluation revealed primary diffuse leptomeningeal non-Hodgkin's T-cell
      lymphoma.

PMID- 25750226
TI  - Kyphoscoliosis: looking beyond the spine.

PMID- 25750227
TI  - 18F-FDG-PET-positive adrenal tumour.

PMID- 25750228
TI  - Neonatal thyrotoxicosis caused by maternal autoimmune hyperthyroidism.
AB  - Neonatal immune hyperthyroidism is a rare but potentially fatal condition. It
      occurs in 1-5% of infants born to women with Graves' disease (GD). In most of the
      cases it is due to maternal antibodies transferred from the mother into the fetal
      compartment, stimulating the fetal thyroid by binding thyrotropin (thyroid
      stimulating hormone, TSH) receptor. We present a case of neonatal thyrotoxicosis
      due to maternal GD detected at 25 days of age and discuss the potential pitfalls
      in the diagnosis.

PMID- 25750229
TI  - Forging patterns and making waves from biology to geology: a commentary on Turing
      (1952) 'The chemical basis of morphogenesis'.
AB  - Alan Turing was neither a biologist nor a chemist, and yet the paper he published
      in 1952, 'The chemical basis of morphogenesis', on the spontaneous formation of
      patterns in systems undergoing reaction and diffusion of their ingredients has
      had a substantial impact on both fields, as well as in other areas as disparate
      as geomorphology and criminology. Motivated by the question of how a spherical
      embryo becomes a decidedly non-spherical organism such as a human being, Turing
      devised a mathematical model that explained how random fluctuations can drive the
      emergence of pattern and structure from initial uniformity. The spontaneous
      appearance of pattern and form in a system far away from its equilibrium state
      occurs in many types of natural process, and in some artificial ones too. It is
      often driven by very general mechanisms, of which Turing's model supplies one of
      the most versatile. For that reason, these patterns show striking similarities in
      systems that seem superficially to share nothing in common, such as the stripes
      of sand ripples and of pigmentation on a zebra skin. New examples of 'Turing
      patterns' in biology and beyond are still being discovered today. This commentary
      was written to celebrate the 350th anniversary of the journal Philosophical
      Transactions of the Royal Society.

PMID- 25750230
TI  - Every inch a finch: a commentary on Grant (1993) 'Hybridization of Darwin's
      finches on Isla Daphne Major, Galapagos'.
AB  - One of the most familiar features of the natural world is that most animals and
      plants fall into distinct categories known as species. The attempt to understand
      the nature of species and the origin of new species was the enterprise that drove
      the early development of evolutionary biology and has continued to be a major
      focus of research. Individuals belonging to the same species usually share a
      distinctive appearance and way of life, and they can mate together successfully
      and produce viable offspring. New species may evolve, therefore, either through
      ecological divergence or through sexual isolation. The balance between these
      processes will depend on the extent of hybridization, especially in the early
      stages of divergence. Detecting and measuring hybridization in natural
      populations, however, requires intensive, long-term field programmes that are
      seldom undertaken, leaving a gap in our understanding of species formation. The
      finch community of a small, isolated island in the Galapagos provided an
      opportunity to discover how frequently hybridization takes place between closely
      related species in a pristine location, and Peter Grant's paper, published in
      Philosophical Transactions B in 1993, reports the observations that he and his
      collaborators made during the first 20 years of what is now one of the classical
      studies of evolution in action. This commentary was written to celebrate the
      350th anniversary of the journal Philosophical Transactions of the Royal Society.

PMID- 25750231
TI  - How mathematical epidemiology became a field of biology: a commentary on Anderson
      and May (1981) 'The population dynamics of microparasites and their invertebrate
      hosts'.
AB  - We discuss the context, content and importance of the paper 'The population
      dynamics of microparasites and their invertebrate hosts', by R. M. Anderson and
      R. M. May, published in the Philosophical Transactions of the Royal Society as a
      stand-alone issue in 1981. We do this from the broader perspective of the study
      of infectious disease dynamics, rather than the specific perspective of the
      dynamics of insect pathogens. We argue that their 1981 paper fits seamlessly in
      the systematic study of infectious disease dynamics that was initiated by the
      authors in 1978, combining effective use of simple mathematical models, firmly
      rooted in biology, with observable or empirically measurable ingredients and
      quantities, and promoting extensive capacity building. This systematic approach,
      taking ecology and biology rather than applied mathematics as the motivation for
      advance, proved essential for the maturation of the field, and culminated in
      their landmark textbook of 1991. This commentary was written to celebrate the
      350th anniversary of the journal Philosophical Transactions of the Royal Society.

PMID- 25750232
TI  - Focusing by shape change in the lens of the eye: a commentary on Young (1801) 'On
      the mechanism of the eye'.
AB  - In his Bakerian Lecture paper of 1801, Thomas Young provided the best account up
      to that time of the eye's optical system, including refraction by the cornea and
      the surfaces of the lens. He built a device, an optometer, for determining the
      eye's state of focus, making it possible to prescribe appropriate correction
      lenses. His main contribution, however, was to show that accommodation, the eye's
      focusing mechanism, was not the result of changes to the curvature of the cornea,
      nor to the length of the eye, but was due entirely to changes in the shape of the
      lens, which he described with impressive accuracy. He was wrong, however, in
      believing that the reason the lens bulges when focusing on near objects was
      because it behaved as a contracting muscle. Half a century later, Helmholtz
      showed that the lens bulges not by its own contraction, but when it is relaxed as
      a result of contraction of newly discovered circular muscles in the ciliary body.
      This commentary was written to celebrate the 350th anniversary of the journal
      Philosophical Transactions of the Royal Society.

PMID- 25750233
TI  - The beginning of connectomics: a commentary on White et al. (1986) 'The structure
      of the nervous system of the nematode Caenorhabditis elegans'.
AB  - The article 'Structure of the nervous system of the nematode Caenorhabditis
      elegans' (aka 'The mind of a worm') by White et al., published for the first time
      the complete set of synaptic connections in the nervous system of an animal. The
      work was carried out as part of a programme to begin to understand how genes
      determine the structure of a nervous system and how a nervous system creates
      behaviour. It became a major stimulus to the field of C. elegans research, which
      has since contributed insights into all areas of biology. Twenty-six years
      elapsed before developments, notably more powerful computers, made new studies of
      this kind possible. It is hoped that one day knowledge of synaptic structure, the
      connectome, together with results of many other investigations, will lead to an
      understanding of the human brain. This commentary was written to celebrate the
      350th anniversary of the journal Philosophical Transactions of the Royal Society.

PMID- 25750234
TI  - Gas valves, forests and global change: a commentary on Jarvis (1976) 'The
      interpretation of the variations in leaf water potential and stomatal conductance
      found in canopies in the field'.
AB  - Microscopic turgor-operated gas valves on leaf surfaces-stomata-facilitate gas
      exchange between the plant and the atmosphere, and respond to multiple
      environmental and endogenous cues. Collectively, stomatal activities affect
      everything from the productivity of forests, grasslands and crops to biophysical
      feedbacks between land surface vegetation and climate. In 1976, plant
      physiologist Paul Jarvis reported an empirical model describing stomatal
      responses to key environmental and plant conditions that predicted the flux of
      water vapour from leaves into the surrounding atmosphere. Subsequent theoretical
      advances, building on this earlier approach, established the current paradigm for
      capturing the physiological behaviour of stomata that became incorporated into
      sophisticated models of land carbon cycling. However, these models struggle to
      accurately predict observed trends in the physiological responses of Northern
      Hemisphere forests to recent atmospheric CO2 increases, highlighting the need for
      improved representation of the role of stomata in regulating forest-climate
      interactions. Bridging this gap between observations and theory as atmospheric
      CO2 rises and climate change accelerates creates challenging opportunities for
      the next generation of physiologists to advance planetary ecology and climate
      science. This commentary was written to celebrate the 350th anniversary of the
      journal Philosophical Transactions of the Royal Society.

PMID- 25750235
TI  - Extraordinary fossils reveal the nature of Cambrian life: a commentary on
      Whittington (1975) 'The enigmatic animal Opabinia regalis, Middle Cambrian,
      Burgess Shale, British Columbia'.
AB  - Harry Whittington's 1975 monograph on Opabinia was the first to highlight how
      some of the Burgess Shale animals differ markedly from those that populate
      today's oceans. Categorized by Stephen J. Gould as a 'weird wonder' (Wonderful
      life, 1989) Opabinia, together with other unusual Burgess Shale fossils,
      stimulated ongoing debates about the early evolution of the major animal groups
      and the nature of the Cambrian explosion. The subsequent discovery of a number of
      other exceptionally preserved fossil faunas of Cambrian and early Ordovician age
      has significantly augmented the information available on this critical interval
      in the history of life. Although Opabinia initially defied assignment to any
      group of modern animals, it is now interpreted as lying below anomalocaridids on
      the stem leading to the living arthropods. This commentary was written to
      celebrate the 350th anniversary of the journal Philosophical Transactions of the
      Royal Society.

PMID- 25750236
TI  - A model model: a commentary on DiFrancesco and Noble (1985) 'A model of cardiac
      electrical activity incorporating ionic pumps and concentration changes'.
AB  - This paper summarizes the advances made by the DiFrancesco and Noble (DFN) model
      of cardiac cellular electrophysiology, which was published in Philosophical
      Transactions B in 1985. This model was developed at a time when the introduction
      of new techniques and provision of experimental data had resulted in an explosion
      of knowledge about the cellular and biophysical properties of the heart. It
      advanced the cardiac modelling field from a period when computer models
      considered only the voltage-dependent channels in the surface membrane. In
      particular, it included a consideration of changes of both intra- and
      extracellular ionic concentrations. In this paper, we summarize the most
      important contributions of the DiFrancesco and Noble paper. We also describe how
      computer modelling has developed subsequently with the extension from the single
      cell to the whole heart as well as its use in understanding disease and
      predicting the effects of pharmaceutical interventions. This commentary was
      written to celebrate the 350th anniversary of the journal Philosophical
      Transactions of the Royal Society. 

PMID- 25750237
TI  - From plant extract to molecular panacea: a commentary on Stone (1763) 'An account
      of the success of the bark of the willow in the cure of the agues'.
AB  - The application of aspirin-like drugs in modern medicine is very broad,
      encompassing the treatment of inflammation, pain and a variety of cardiovascular
      conditions. Although anecdotal accounts of willow bark extract as an anti
      inflammatory drug have occurred since written records began (for example by
      Hippocrates), the first convincing demonstration of a potent anti-pyretic effect
      of willow bark containing salicylates was made by the English cleric Edward Stone
      in the late eighteenth century. Here, we discuss the route to optimizing and
      understanding the mechanism of action of anti-inflammatory drugs that have their
      origins in Stone's seminal study, 'An account of the success of the bark of the
      willow in the cure of agues'. This commentary was written to celebrate the 350th
      anniversary of the journal Philosophical Transactions of the Royal Society. 

PMID- 25750238
TI  - The early evolution of land plants, from fossils to genomics: a commentary on
      Lang (1937) 'On the plant-remains from the Downtonian of England and Wales'.
AB  - During the 1920s, the botanist W. H. Lang set out to collect and investigate some
      very unpromising fossils of uncertain affinity, which predated the known
      geological record of life on land. His discoveries led to a landmark publication
      in 1937, 'On the plant-remains from the Downtonian of England and Wales', in
      which he revealed a diversity of small fossil organisms of great simplicity that
      shed light on the nature of the earliest known land plants. These and subsequent
      discoveries have taken on new relevance as botanists seek to understand the plant
      genome and the early evolution of fundamental organ systems. Also, our developing
      knowledge of the composition of early land-based ecosystems and the interactions
      among their various components is contributing to our understanding of how life
      on land affects key Earth Systems (e.g. carbon cycle). The emerging paradigm is
      one of early life on land dominated by microbes, small bryophyte-like organisms
      and lichens. Collectively called cryptogamic covers, these are comparable with
      those that dominate certain ecosystems today. This commentary was written to
      celebrate the 350th anniversary of the journal Philosophical Transactions of the
      Royal Society.

PMID- 25750239
TI  - The unseen world: reflections on Leeuwenhoek (1677) 'Concerning little animals'.
AB  - Leeuwenhoek's 1677 paper, the famous 'letter on the protozoa', gives the first
      detailed description of protists and bacteria living in a range of environments.
      The colloquial, diaristic style conceals the workings of a startlingly original
      experimental mind. Later scientists could not match the resolution and clarity of
      Leeuwenhoek's microscopes, so his discoveries were doubted or even dismissed over
      the following centuries, limiting their direct influence on the history of
      biology; but work in the twentieth century confirmed Leeuwenhoek's discovery of
      bacterial cells, with a resolution of less than 1 um. Leeuwenhoek delighted most
      in the forms, interactions and behaviour of his little 'animalcules', which
      inhabited a previously unimagined microcosmos. In these reflections on the
      scientific reach of Leeuwenhoek's ideas and observations, I equate his questions
      with the preoccupations of our genomic era: what is the nature of Leeuwenhoek's
      animalcules, where do they come from, how do they relate to each other? Even with
      the powerful tools of modern biology, the answers are far from resolved-these
      questions still challenge our understanding of microbial evolution. This
      commentary was written to celebrate the 350th anniversary of the journal
      Philosophical Transactions of the Royal Society.

PMID- 25750240
TI  - From high symmetry to high resolution in biological electron microscopy: a
      commentary on Crowther (1971) 'Procedures for three-dimensional reconstruction of
      spherical viruses by Fourier synthesis from electron micrographs'.
AB  - Elucidation of the structure of biological macromolecules and larger assemblies
      has been essential to understanding the roles they play in living processes.
      Methods for three-dimensional structure determination of biological assemblies
      from images recorded in the electron microscope were therefore a key development.
      In his paper published in Philosophical Transactions B in 1971, Crowther
      described new computational procedures applied to the first three-dimensional
      reconstruction of an icosahedral virus from images of virus particles preserved
      in negative stain. The method for determining the relative orientation of
      randomly oriented particles and combining their images for reconstruction
      exploited the high symmetry of the virus particle. Computational methods for
      image analysis have since been extended to include biological assemblies without
      symmetry. Further experimental advances, combined with image analysis, have led
      to the method of cryomicroscopy, which is now used by structural biologists to
      study the structure and dynamics of biological machines and assemblies in atomic
      detail. This commentary was written to celebrate the 350th anniversary of the
      journal Philosophical Transactions of the Royal Society. 

PMID- 25750241
TI  - The prevention and eradication of smallpox: a commentary on Sloane (1755) 'An
      account of inoculation'.
AB  - Sir Hans Sloane's account of inoculation as a means to protect against smallpox
      followed several earlier articles published in Philosophical Transactions on this
      procedure. Inoculation (also called 'variolation') involved the introduction of
      small amounts of infectious material from smallpox vesicles into the skin of
      healthy subjects, with the goal of inducing mild symptoms that would result in
      protection against the more severe naturally acquired disease. It began to be
      practised in England in 1721 thanks to the efforts of Lady Mary Wortley Montagu
      who influenced Sloane to promote its use, including the inoculation of the royal
      family's children. When Edward Jenner's inoculation with the cow pox
      ('vaccination') followed 75 years later as a safer yet equally effective
      procedure, the scene was set for the eventual control of smallpox epidemics
      culminating in the worldwide eradication of smallpox in 1977, officially
      proclaimed by WHO in 1980. Here, we discuss the significance of variolation and
      vaccination with respect to scientific, public health and ethical controversies
      concerning these 'weapons of mass protection'. This commentary was written to
      celebrate the 350th anniversary of the journal Philosophical Transactions of the
      Royal Society. 

PMID- 25750242
TI  - Deciphering death: a commentary on Gompertz (1825) 'On the nature of the function
      expressive of the law of human mortality, and on a new mode of determining the
      value of life contingencies'.
AB  - In 1825, the actuary Benjamin Gompertz read a paper, 'On the nature of the
      function expressive of the law of human mortality, and on a new mode of
      determining the value of life contingencies', to the Royal Society in which he
      showed that over much of the adult human lifespan, age-specific mortality rates
      increased in an exponential manner. Gompertz's work played an important role in
      shaping the emerging statistical science that underpins the pricing of life
      insurance and annuities. Latterly, as the subject of ageing itself became the
      focus of scientific study, the Gompertz model provided a powerful stimulus to
      examine the patterns of death across the life course not only in humans but also
      in a wide range of other organisms. The idea that the Gompertz model might
      constitute a fundamental 'law of mortality' has given way to the recognition that
      other patterns exist, not only across the species range but also in advanced old
      age. Nevertheless, Gompertz's way of representing the function expressive of the
      pattern of much of adult mortality retains considerable relevance for studying
      the factors that influence the intrinsic biology of ageing. This commentary was
      written to celebrate the 350th anniversary of the journal Philosophical
      Transactions of the Royal Society.

PMID- 25750243
TI  - Celebrating 350 years of Philosophical Transactions: life sciences papers.

PMID- 25750244
TI  - Foreseeing fates: a commentary on Manton (1928) 'On the embryology of a mysid
      crustacean, Hemimysis lamornae'.
AB  - Sidnie Manton became best known for her work on arthropod locomotion, and for
      proposing radical views on the evolution of arthropods that were accepted for a
      generation. However, her early training was as an embryologist, and the work that
      she carried out at the beginning of her career still stands as one of the major
      twentieth century contributions to the study of crustacean embryology. Here, I
      review her first major paper, largely completed while she was a graduate student,
      describing embryonic development in Hemimysis lamornae, a small shrimp-like
      animal found in the seas around the UK. The clarity of her writing and the
      quality of her figures set a standard that laid the basis for subsequent work,
      and although not all of her conclusions have stood the test of time, they remain
      a standard reference for work today. This commentary was written to celebrate the
      350th anniversary of the journal Philosophical Transactions of the Royal Society.

PMID- 25750245
TI  - Medawar's legacy to cellular immunology and clinical transplantation: a
      commentary on Billingham, Brent and Medawar (1956) 'Quantitative studies on
      tissue transplantation immunity. III. Actively acquired tolerance'.
AB  - 'Quantitative studies on tissue transplantation immunity. III. Actively acquired
      tolerance', published in Philosophical Transactions B in 1956 by Peter Medawar
      and his colleagues, PhD graduate Leslie Brent and postdoctoral fellow Rupert
      Billingham, is a full description of the concept of acquired transplantation
      tolerance. Their 1953 Nature paper (Billingham RE et al. 1953 Nature 172, 603
      606. (doi:10.1038/172603a0)) had provided initial evidence with experimental
      results from a small number of neonatal mice, with mention of similar findings in
      chicks. The Philosophical Transactions B 1956 paper is clothed with an
      astonishing amount of further experimental detail. It is written in Peter
      Medawar's landmark style: witty, perceptive and full of images that can be
      recalled even when details of the supporting information have faded. Those images
      are provided not just by a series of 20 colour plates showing skin graft
      recipient mice, rats, rabbits, chickens and duck, bearing fur or plumage of donor
      origin, but by his choice of metaphor, simile and analogy to express the
      questions being addressed and the interpretation of their results, along with
      those of relevant published data and his prescient ideas of what the results
      might portend. This work influenced both immunology researchers and clinicians
      and helped to lay the foundations for successful transplantation programmes. It
      led to the award of a Nobel prize in 1960 to Medawar, and subsequently to several
      scientists who advanced these areas. This commentary was written to celebrate the
      350th anniversary of the journal Philosophical Transactions of the Royal Society.

PMID- 25750246
TI  - Memory, modelling and Marr: a commentary on Marr (1971) 'Simple memory: a theory
      of archicortex'.
AB  - David Marr's theory of the archicortex, a brain structure now more commonly known
      as the hippocampus and hippocampal formation, is an epochal contribution to
      theoretical neuroscience. Addressing the problem of how information about 10 000
      events could be stored in the archicortex during the day so that they can be
      retrieved using partial information and then transferred to the neocortex
      overnight, the paper presages a whole wealth of later empirical and theoretical
      work, proving impressively prescient. Despite this impending success, Marr later
      apparently grew dissatisfied with this style of modelling, but he went on to make
      seminal suggestions that continue to resonate loudly throughout the field of
      theoretical neuroscience. We describe Marr's theory of the archicortex and his
      theory of theories, setting them into their original and a contemporary context,
      and assessing their impact. This commentary was written to celebrate the 350th
      anniversary of the journal Philosophical Transactions of the Royal Society.

PMID- 25750248
TI  - The "Right Stuff" Revisited: What Have We Learned About the Determinants of Daily
      Functioning in Schizophrenia?
AB  - It has been about 15 years since we published our article asking whether we are
      measuring the "Right Stuff" as we search for predictors and determinants of
      functional outcome in schizophrenia. At that time, we raised the question as to
      whether the neurocognitive assessments used to study outcome in schizophrenia
      were too narrow to capture the wide variability in factors that determine daily
      functioning. While the study of the determinants of functioning in schizophrenia
      has grown and matured, we are struck by 3 aspects of the article that evolved in
      different directions. First, the selection of outcome domains in the Right Stuff
      meta-analysis reflects a focus at that time on predictors of psychiatric
      rehabilitation. Second, expansion beyond traditional neurocognitive domains
      occurred in one suggested area (social cognition), but not another (learning
      potential). Third, the field has responded assertively to the recommendation to
      evaluate more informed and informative theoretical models. 

PMID- 25750250
TI  - Dimitrios Trichopoulos: in memoriam (1938-2014).

PMID- 25750247
TI  - Modeling determinants of medication attitudes and poor adherence in early
      nonaffective psychosis: implications for intervention.
AB  - We aimed to design a multimodal intervention to improve adherence following first
      episode psychosis, consistent with current evidence. Existing literature
      identified medication attitudes, insight, and characteristics of support as
      important determinants of adherence to medication: we examined medication
      attitudes, self-esteem, and insight in an early psychosis cohort better to
      understand their relationships. Existing longitudinal data from 309 patients with
      early Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition,
      nonaffective psychosis (83% first episode) were analyzed to test the hypothesis
      that medication attitudes, while meaningfully different from "insight,"
      correlated with insight and self-esteem, and change in each influenced the
      others. Rosenberg Self-Esteem Scale, Birchwood Insight Scale, and Positive and
      Negative Syndrome Scale insight were assessed at presentation, after 6 weeks and
      3 and 18 months. Drug Attitudes Inventory (DAI) and treatment satisfaction were
      rated from 6 weeks onward. Structural equation models of their relationships were
      compared. Insight measures' and DAI's predictive validity were compared against
      relapse, readmission, and remission. Analysis found five latent constructs best
      fitted the data: medication attitudes, self-esteem, accepting need for treatment,
      self-rated insight, and objective insight. All were related and each affected the
      others as it changed, except self-esteem and medication attitudes. Low self
      reported insight at presentation predicted readmission. Good 6-week insight
      (unlike drug attitudes) predicted remission. Literature review and data modeling
      indicated that a multimodal intervention using motivational interviewing, online
      psychoeducation, and SMS text medication reminders to enhance adherence without
      damaging self-concept was feasible and appropriate. 

PMID- 25750251
TI  - Opportunities for translational epidemiology: the important role of observational
      studies to advance precision oncology.
AB  - Within current oncology practice, several genomic applications are being used to
      inform treatment decisions with molecularly targeted therapies in breast, lung,
      colorectal, melanoma, and other cancers. This commentary introduces a conceptual
      framework connecting the full spectrum of biomedical research disciplines,
      including fundamental laboratory research, clinical trials, and observational
      studies in the translation of genomic applications into clinical practice. The
      conceptual framework illustrates the contribution that well-designed
      observational epidemiologic studies provide to the successful translation of
      these applications, and characterizes the role observational epidemiology plays
      in driving the dynamic and iterative bench-to-bedside, and bedside-to-bench
      translation continuum. We also discuss how the principles of this conceptual
      model, emphasizing integration of multidisciplinary research, can be applied to
      the evolving paradigm in "precision oncology" focusing on multiplex tumor
      sequencing, and we identify opportunities for observational studies to contribute
      to the successful and efficient translation of this paradigm.Cancer Epidemiol
      Biomarkers Prev; 24(3); 484-9. (c)2015 AACR. 

PMID- 25750252
TI  - BOLD Variability is Related to Dopaminergic Neurotransmission and Cognitive
      Aging.
AB  - Dopamine (DA) losses are associated with various aging-related cognitive
      deficits. Typically, higher moment-to-moment brain signal variability in large
      scale patterns of voxels in neocortical regions is linked to better cognitive
      performance and younger adult age, yet the physiological mechanisms regulating
      brain signal variability are unknown. We explored the relationship among adult
      age, DA availability, and blood oxygen level-dependent (BOLD) signal variability,
      while younger and older participants performed a spatial working memory (SWM)
      task. We quantified striatal and extrastriatal DA D1 receptor density with
      [(11)C]SCH23390 and positron emission tomography in all participants. We found
      that BOLD variability in a neocortical region was negatively related to age and
      positively related to SWM performance. In contrast, BOLD variability in
      subcortical regions and bilateral hippocampus was positively related to age and
      slower responses, and negatively related to D1 density in caudate and
      dorsolateral prefrontal cortex. Furthermore, BOLD variability in neocortical
      regions was positively associated with task-related disengagement of the default
      mode network, a network whose activation needs to be suppressed for efficient SWM
      processing. Our results show that age-related DA losses contribute to changes in
      brain signal variability in subcortical regions and suggest a potential
      mechanism, by which neocortical BOLD variability supports cognitive performance. 

PMID- 25750254
TI  - Age-Dependent Long-Term Potentiation Deficits in the Prefrontal Cortex of the
      Fmr1 Knockout Mouse Model of Fragile X Syndrome.
AB  - The most common inherited monogenetic cause of intellectual disability is Fragile
      X syndrome (FXS). The clinical symptoms of FXS evolve with age during adulthood;
      however, neurophysiological data exploring this phenomenon are limited. The Fmr1
      knockout (Fmr1KO) mouse models FXS, but studies in these mice of prefrontal
      cortex (PFC) function are underrepresented, and aging linked data are absent. We
      studied synaptic physiology and activity-dependent synaptic plasticity in the
      medial PFC of Fmr1KO mice from 2 to 12 months. In young adult Fmr1KO mice, NMDA
      receptor (NMDAR)-mediated long-term potentiation (LTP) is intact; however, in 12
      month-old mice this LTP is impaired. In parallel, there was an increase in the
      AMPAR/NMDAR ratio and a concomitant decrease of synaptic NMDAR currents in 12
      month-old Fmr1KO mice. We found that acute pharmacological blockade of mGlu5
      receptor in 12-month-old Fmr1KO mice restored a normal AMPAR/NMDAR ratio and LTP.
      Taken together, the data reveal an age-dependent deficit in LTP in Fmr1KO mice,
      which may correlate to some of the complex age-related deficits in FXS.

PMID- 25750255
TI  - Distributed Cortical Phase Synchronization in the EEG Reveals Parallel Attention
      and Working Memory Processes Involved in the Attentional Blink.
AB  - Attentional blink (AB) describes a visuo-perceptual phenomenon in which the
      second of 2 targets within a rapid serial visual presentation stream is not
      detected. There are several cognitive models attempting to explain the
      fundamentals of this information processing bottleneck. Here, we used
      electroencephalographic recordings and the analysis of interregional phase
      synchronization of rhythmical brain activity to investigate the neural bases of
      the AB. By investigating the time course of interregional phase synchronization
      separately for trials in which participants failed to report the second target
      correctly (AB trials) and trials in which no AB occurred, and by clustering
      interregional connections based on their functional similarity, it was possible
      to define several distinct cortical networks. Analyzing these networks comprising
      phase synchronization--over a large spectrum of brain frequencies from theta to
      gamma activity--it was possible to identify neural correlates for cognitive
      subfunctions involved in the AB, such as the encoding of targets into working
      memory, tuning of attentional filters, and the recruitment of general cognitive
      resources. This parallel activation of functionally distinct neural processes
      substantiates the eligibility of several cognitive models on the AB.

PMID- 25750253
TI  - Cognitive Control Network Contributions to Memory-Guided Visual Attention.
AB  - Visual attentional capacity is severely limited, but humans excel in familiar
      visual contexts, in part because long-term memories guide efficient deployment of
      attention. To investigate the neural substrates that support memory-guided visual
      attention, we performed a set of functional MRI experiments that contrast long
      term, memory-guided visuospatial attention with stimulus-guided visuospatial
      attention in a change detection task. Whereas the dorsal attention network was
      activated for both forms of attention, the cognitive control network(CCN) was
      preferentially activated during memory-guided attention. Three posterior nodes in
      the CCN, posterior precuneus, posterior callosal sulcus/mid-cingulate, and
      lateral intraparietal sulcus exhibited the greatest specificity for memory-guided
      attention. These 3 regions exhibit functional connectivity at rest, and we
      propose that they form a subnetwork within the broader CCN. Based on the task
      activation patterns, we conclude that the nodes of this subnetwork are
      preferentially recruited for long-term memory guidance of visuospatial attention.

PMID- 25750256
TI  - Supplementary Eye Field Encodes Confidence in Decisions Under Risk.
AB  - Choices are made with varying degrees of confidence, a cognitive signal
      representing the subjective belief in the optimality of the choice. Confidence
      has been mostly studied in the context of perceptual judgments, in which choice
      accuracy can be measured using objective criteria. Here, we study confidence in
      subjective value-based decisions. We recorded in the supplementary eye field
      (SEF) of monkeys performing a gambling task, where they had to use subjective
      criteria for placing bets. We found neural signals in the SEF that explicitly
      represent choice confidence independent from reward expectation. This confidence
      signal appeared after the choice and diminished before the choice outcome. Most
      of this neuronal activity was negatively correlated with confidence, and was
      strongest in trials on which the monkey spontaneously withdrew his choice. Such
      confidence-related activity indicates that the SEF not only guides saccade
      selection, but also evaluates the likelihood that the choice was optimal. This
      internal evaluation influences decisions concerning the willingness to bear later
      costs that follow from the choice or to avoid them. More generally, our findings
      indicate that choice confidence is an integral component of all forms of decision
      making, whether they are based on perceptual evidence or on value estimations. 

PMID- 25750258
TI  - Integration of Distinct Objects in Visual Working Memory Depends on Strong
      Objecthood Cues Even for Different-Dimension Conjunctions.
AB  - What makes an integrated object in visual working memory (WM)? Past evidence
      suggested that WM holds all features of multidimensional objects together, but
      struggles to integrate color-color conjunctions. This difficulty was previously
      attributed to a challenge in same-dimension integration, but here we argue that
      it arises from the integration of 2 distinct objects. To test this, we examined
      the integration of distinct different-dimension features (a colored square and a
      tilted bar). We monitored the contralateral delay activity, an event-related
      potential component sensitive to the number of objects in WM. The results
      indicated that color and orientation belonging to distinct objects in a shared
      location were not integrated in WM (Experiment 1), even following a common fate
      Gestalt cue (Experiment 2). These conjunctions were better integrated in a less
      demanding task (Experiment 3), and in the original WM task, but with a less
      individuating version of the original stimuli (Experiment 4). Our results
      identify the critical factor in WM integration at same- versus separate-objects,
      rather than at same- versus different-dimensions. Compared with the perfect
      integration of an object's features, the integration of several objects is
      demanding, and depends on an interaction between the grouping cues and task
      demands, among other factors. 

PMID- 25750257
TI  - Altered Structural Brain Networks in Tuberous Sclerosis Complex.
AB  - Tuberous sclerosis complex (TSC) is characterized by benign hamartomas in
      multiple organs including the brain and its clinical phenotypes may be associated
      with abnormal neural connections. We aimed to provide the first detailed findings
      on disrupted structural brain networks in TSC patients. Structural whole-brain
      connectivity maps were constructed using structural and diffusion MRI in 20 TSC
      (age range: 3-24 years) and 20 typically developing (TD; 3-23 years) subjects. We
      assessed global (short- and long-association and interhemispheric fibers) and
      regional white matter connectivity, and performed graph theoretical analysis
      using gyral pattern- and atlas-based node parcellations. Significantly higher
      mean diffusivity (MD) was shown in TSC patients than in TD controls throughout
      the whole brain and positively correlated with tuber load severity. A significant
      increase in MD was mainly influenced by an increase in radial diffusivity.
      Furthermore, interhemispheric connectivity was particularly reduced in TSC, which
      leads to increased network segregation within hemispheres. TSC patients with
      developmental delay (DD) showed significantly higher MD than those without DD
      primarily in intrahemispheric connections. Our analysis allows non-biased
      determination of differential white matter involvement, which may provide better
      measures of "lesion load" and lead to a better understanding of disease
      mechanisms. 

PMID- 25750260
TI  - Novel human homologues of p47phox and p67phox participate in activation of
      superoxide-producing NADPH oxidases.

PMID- 25750261
TI  - IPP5, a novel protein inhibitor of protein phosphatase 1, promotes G1/S
      progression in a Thr-40-dependent manner.

PMID- 25750262
TI  - Identification of small molecule inhibitors of pre-mRNA splicing.

PMID- 25750259
TI  - Concept Representation Reflects Multimodal Abstraction: A Framework for Embodied
      Semantics.
AB  - Recent research indicates that sensory and motor cortical areas play a
      significant role in the neural representation of concepts. However, little is
      known about the overall architecture of this representational system, including
      the role played by higher level areas that integrate different types of sensory
      and motor information. The present study addressed this issue by investigating
      the simultaneous contributions of multiple sensory-motor modalities to semantic
      word processing. With a multivariate fMRI design, we examined activation
      associated with 5 sensory-motor attributes--color, shape, visual motion, sound,
      and manipulation--for 900 words. Regions responsive to each attribute were
      identified using independent ratings of the attributes' relevance to the meaning
      of each word. The results indicate that these aspects of conceptual knowledge are
      encoded in multimodal and higher level unimodal areas involved in processing the
      corresponding types of information during perception and action, in agreement
      with embodied theories of semantics. They also reveal a hierarchical system of
      abstracted sensory-motor representations incorporating a major division between
      object interaction and object perception processes.

PMID- 25750263
TI  - Budding yeast Swe1 is involved in the control of mitotic spindle elongation and
      is regulated by Cdc14 phosphatase during mitosis.

PMID- 25750264
TI  - Zinc-binding domain-dependent, deaminase-independent actions of apolipoprotein B
      mRNA-editing enzyme, catalytic polypeptide 2 (Apobec2), mediate its effect on
      zebrafish retina regeneration.

PMID- 25750265
TI  - ASXL1 represses retinoic acid receptor-mediated transcription through associating
      with HP1 and LSD1.

PMID- 25750266
TI  - HDAC3-dependent reversible lysine acetylation of cardiac myosin heavy chain
      isoforms modulates their enzymatic and motor activity.

PMID- 25750267
TI  - Role of inflammatory infiltrates in triple negative breast cancer.
AB  - Triple negative breast cancer (TNBC) is a heterogenous disease often
      characterised by aggressive biology and poor prognosis. Efforts to precisely
      treat TNBC have been compounded by the lack of specific therapeutic molecular
      targets. Recent transcriptomic studies have revealed, among others, an
      immunomodulatory subtype of TNBC, whereby activated immune response genes are
      associated with good prognosis. Since then, a great deal of effort has been made
      to understand the immune microenvironment of some TNBC subtype, which comprises
      several immune cell populations including lymphocytes and macrophages. There is
      increasing evidence that the basal subtype may be significantly regulated by
      tumour-infiltrating T-cells and that high levels of tumour-infiltrating CD8+ T
      cells may be a reflection of improved prognosis with chemotherapy sensitivity in
      TNBC. On the other hand, tumour-associated macrophages have been associated with
      a relatively poor outcome in TNBC. Comparison of the immune signatures in TNBC
      with non-TNBC may furthermore help us to understand these immune mechanisms
      potentially leading to new therapeutic approaches. Within this short review, we
      discuss the current scientific evidence regarding (a) the role of tumour
      infiltrating lymphocytes in the clinical outcome in TNBC and (b) the newly
      discovered immunomodulatory genotype that may provide for a therapeutic target in
      TNBC. 

PMID- 25750269
TI  - Topics in chemotherapy, molecular-targeted therapy, and immunotherapy for newly
      diagnosed glioblastoma multiforme.
AB  - Glioblastoma multiforme (GBM) is the most common primary brain tumor in adults,
      and it is associated with poor survival. The standard therapy for newly-diagnosed
      GBM is radiotherapy with concurrent temozolomide following maximal surgical
      resection. To improve the outcome of these patients, combinations of the standard
      therapy plus molecular-targeted agents have been tested in clinical trials.
      However, the addition of gefitinib to the standard therapy did not appear to
      improve clinical outcome, and the standard therapy plus bevacizumab showed no
      improvement in overall survival, although a 4-month improvement in progression
      free survival (PFS) was observed. Phase II data have indicated the potential
      efficacy of talampanel combined with the standard therapy for patients with newly
      diagnosed GBM, and these findings are awaiting validation in phase III trials. In
      addition, phase II trials have demonstrated that adjuvant immunotherapy is
      effective and tolerable for treatment of patients with GBM. In this article, we
      discuss topics in chemotherapy, molecular-targeted therapy, and immunotherapy for
      patients with newly-diagnosed GBM. 

PMID- 25750268
TI  - Perivascular epithelioid tumours (PEComas) of the gynaecological tract.
AB  - Perivascular epithelioid tumours (PEComas) of the gynaecological tract are rare
      tumours which were first recognised and diagnosed within the last 20 years. They
      represent a unique diagnostic challenge with regard to their accurate and
      reproducible distinction from more common entities such as smooth muscle tumours
      of the uterine corpus. In this review article, we trace the development of the
      concept of the PEComa tumour family, highlight what is known about extra
      gynaecological tract PEComa at an immunohistochemical, molecular and therapeutic
      level and then present a summary of all reported cases of gynaecological tract
      PEComa to date. In the summary, we highlight rare subtypes of gynaecological
      tract PEComa and compare the performances of extant prognostic classification
      systems for malignancy in these tumours.

PMID- 25750270
TI  - Diagnostic potential of ancillary molecular testing in differentiation of benign
      and malignant thyroid nodules.
AB  - Fine needle aspiration (FNA) cytology, being the mainstay to diagnose thyroid
      nodules, does not provide definitive results in a subset of patients. The use of
      molecular markers testing has been described as a useful aid in differentiation
      of thyroid nodules that present with an indeterminate cytodiagnosis. Molecular
      tests, such as the Afirma gene classifier, mutational assay and
      immunohistochemical markers have been increasingly used to further increase the
      accuracy and defer unnecessary surgeries for benign thyroid nodules. However, in
      light of the current literature, their emerging roles in clinical practice are
      limited due to financial and technical limitations. Nevertheless, their
      synergistic implementation can predict the risk of malignancy and yield an
      accurate diagnosis. This review discusses the clinical utility of various
      molecular tests done on FNA indeterminate nodules to avoid diagnostic
      thyroidectomies and warrant the need of future multi-Institutional studies. 

PMID- 25750271
TI  - Co-targeting ER and HER family receptors induces apoptosis in HER2-normal or
      overexpressing breast cancer models.
AB  - BACKGROUND: Estrogen receptor (ER) and human epidermal growth factor receptor
      (HER) family receptors interact in breast cancer; co-targeting these receptors is
      of interest. We previously reported on a synergistic growth inhibition for the
      combination of trastuzumab plus tamoxifen in HER2+/ER+ BT474 cells, but no
      induction of apoptosis. Herein we describe the effects of co-targeting in models
      of differing HER2 overexpression status (MCF7 HER2-normal/ER+, BT474 HER2
      overexpressing/ER+). MATERIALS AND METHODS: Assays of proliferation were carried
      out using WST-1, cell cycle using flow cytometry, and apoptosis by determination
      of sub-G1 population and by annexin-V. RESULTS: Combining a dual HER2/EGFR kinase
      inhibitor with anti-estrogens induces apoptosis of BT474 cells. Furthermore, in
      MCF7 cells, despite HER2-normal status and lack of response to single-agent HER2
      inhibitors, addition of HER2 inhibitors or dual HER2/EGFR inhibitor to anti
      estrogens augments the antiproliferative effect of anti-estrogens, and converts
      the drug effect from cytostatic to apoptosis-inducing. CONCLUSION: ER-HER co
      targeting enhanced the antitumor effects and can bring about effects of targeting
      HER2 in models of HER2-normal breast cancer.

PMID- 25750272
TI  - Transduction of a novel HLA-DRB1*04:05-restricted, WT1-specific TCR gene into
      human CD4+ T cells confers killing activity against human leukemia cells.
AB  - BACKGROUND/AIM: Wilms' tumor gene 1 (WT1) product is a pan-tumor-associated
      antigen. We previously identified WT1 protein-derived promiscuous helper peptide,
      WT1332. Therefore, isolation and characterization of the WT1332-specific T-cell
      receptors (TCRs) are useful to develop broadly applicable TCR gene-based adoptive
      immunotherapy. MATERIALS AND METHODS: A novel HLA-DRB1*04:05-restricted WT1332
      specific TCR gene was cloned and transduced into human CD4+ T-cells by using a
      lentiviral vector. RESULTS: The WT1332-specific TCR-transduced CD4+ T-cells
      showed strong proliferation and Th1-cytokine production in an HLA-DRB1*04:05
      restricted, WT1332-specific manner. Furthermore, the WT1332-specific TCR
      transduced CD4+ T-cells could lyse HLA-DRB1*04:05-positive, WT1-expressing
      leukemia cells in vitro. CONCLUSION: The novel TCR gene cloned here should be a
      promising tool to develop adoptive immunotherapy of WT1332-specific TCR
      transduced CD4+ T-cells for the treatment of WT1-expressing cancer, such as
      leukemia.

PMID- 25750273
TI  - The effect of silibinin in enhancing toxicity of temozolomide and etoposide in
      p53 and PTEN-mutated resistant glioma cell lines.
AB  - Glioblastoma multiforme (GBM) is an intractable brain tumor, associated with poor
      prognosis and low survival rate. Combination therapy such as surgery,
      radiotherapy and temozolomide is considered standard in overcoming this
      aggressive cancer, despite poor prognosis. There is a need to identify potential
      agents, which may augment the chemotherapeutic effects of standard drugs such as
      temozolomide. In this project, we evaluated the effects of silibinin, a natural
      plant component of milk thistle seeds, to potentiate toxic effects of
      chemotherapy drugs such as temozolomide, etoposide and irinotecan on LN229, U87
      and A172 (P53 and phosphatase and tensin homolog (PTEN) -tumor suppressor
      mutated) glioma cell lines. Data from this work suggest that silibinin was
      effective in potentiating the cytotoxic efficacy of temozolomide in LN229, U87
      and A172 cells. While silibinin reduced survivin protein expression only in LN229
      cells, its ability to potentiate cytotoxicity of chemo therapy drugs occurred
      irrespective of survivin protein levels. The data also demonstrated that
      silibinin potentiated the effect of etoposide and but not irinotecan in LN229
      cells. Future research will be required to evaluate the in vivo efficacy of
      silibinin to delineate its mechanism of action and its ability to cross the blood
      brain barrier. 

PMID- 25750274
TI  - MicroRNA expression in differentially metastasizing tumors of the head and neck:
      adenoid cystic versus squamous cell carcinoma.
AB  - BACKGROUND/AIM: Head and neck adenoid cystic carcinoma (HNACC) is a rare
      malignancy of the salivary glands with a tendency to metastasize in lung or liver
      without lymph node involvement, whereas squamous cell carcinoma (HNSCC)
      preferentially metastasizes to locoregional lymph nodes. The expression patterns
      of microRNA, a class of small non-coding RNA transcripts, involved in gene
      regulation and various developmental processes, could be of influence during the
      metastatic process. The aim of the present study was to compare mircoRNA
      expression patterns of HNACC and HNSCC. MATERIALS AND METHODS: In a total of 21
      tissue samples, a genome-wide screening for microRNAs was performed. A microRNA
      array platform was used for the identification of target microRNA. RESULTS: Five
      microRNAs, hsa-MiR-214, hsa-MiR-125a-5p, hsa-MiR-574-3p, hsa-MiR-199a-3p/199b-3p
      and hsa-miR-199a-5p were identified to be over-expressed in HNACC compared to
      HNSCC, whereas hsa-MiR-452 showed a lower expression level. CONCLUSION: Our data
      showed significantly different expression patterns of mircoRNA in HNACC and HNSCC
      supporting the theory of tumor-specific expression and giving hints for different
      clinical behavior.

PMID- 25750275
TI  - Chondroitin sulfate proteoglycan-4 does not protect melanoma cells during
      inhibition of PI3K and mTOR pathways.
AB  - BACKGROUND: Chondroitin sulfate proteoglycan-4 (CSPG4) is commonly expressed in
      melanoma cells and induces melanoma cell proliferation and migration by
      enhancement of activation of the extracellular signal-regulated kinase 1, 2
      (ERK1,2) pathway. The phosphoinositide 3-kinase (PI3K) -protein kinase B (AKT)
      and mammalian target of rapamycin (mTOR) pathways are also frequently de
      regulated in melanoma. We hypothesized that CSPG4, by sustained activation of
      PI3K, may reduce the effect of the dual inhibition of PI3K-AKT and mTOR pathways.
      MATERIALS AND METHODS: CSPG4-negative melanoma cell line WM1552C was transfected
      with CSPG4 and CSPG4 lacking cytoplasmic domain (melanoma-associated chondroitin
      sulfate proteoglycan (MCSP)DeltaCD). To assess the effect of CSPG4 on the mTOR
      pathway, PF-5212384, a dual PI3K/mTOR inhibitor was used. Cell proliferation and
      downstream signaling from mTOR was assayed in the presence of CSPG4. RESULTS:
      Forced CSPG4 expression did not provide any protection to melanoma cells from the
      pharmacological inhibition of mTOR pathway in vitro. In addition, we demonstrated
      that inhibition of signaling molecules downstream of AKT and mTOR was not
      diminished in the presence of CSPG4 when the cells were treated with the
      PI3K/mTOR inhibitor. CONCLUSION: CSPG4 expression does not have any impact on
      survival and signaling activity of melanoma cells during PI3K/mTOR inhibition.

PMID- 25750276
TI  - Remodeling of tannic acid crosslinked collagen type I induces apoptosis in ER+
      breast cancer cells.
AB  - BACKGROUND: The naturally-occurring phytochemical tannic acid (TA) has anticancer
      properties. We have demonstrated that estrogen receptor-positive (ER+) breast
      cancer cells are more sensitive to effects of TA than triple-negative breast
      cancer cells and normal breast epithelial cells. In the present study, cells were
      grown on TA-crosslinked collagen beads. Growing cells remodel collagen and
      release TA, which affects attached cells. MATERIALS AND METHODS: The ER+ breast
      cancer cell line MCF7 and the normal breast epithelial cell line MCF10A were
      grown on TA-crosslinked collagen beads in roller bottles. Concentrations of TA in
      conditioned media were determined. Induced apoptosis was imaged and quantified.
      Caspase gene expression was calculated by real-time polymerase chain reaction
      (PCR). RESULTS: Both cell lines attached and grew on TA-crosslinked collagen
      beads where they remodeled collagen and released TA into surrounding medium.
      Released TA induced caspase-mediated apoptosis. CONCLUSION: TA induced apoptosis
      in a concentration-dependent manner, with ER+ MCF7 cells displaying more
      sensitivity to effects of TA.

PMID- 25750277
TI  - Ectopic expression of protein kinase C-beta sensitizes head and neck squamous
      cell carcinoma to diterpene esters.
AB  - BACKGROUND: The objective of this study was to examine the effect of specific
      Protein kinase C (PKC) isoform re-expression in solid malignancies, particularly
      head and neck squamous cell carcinoma cell lines, and the impact this may have on
      treatment with known activators of PKC. MATERIALS AND METHODS: The constitutive
      expression of PKC isoforms were determined in six head and neck squamous cell
      carcinoma (SCC) cell lines. Cytotoxicity of the prototypic phorbol ester, 12-O
      tetradecanoylphorbol-13-acetate (TPA) and the novel diterpene ester PEP005 was
      established. Viral transduction to re-express PKCbeta isoforms in two of these
      cell lines was performed, and its effect on the sensitivity to the compounds was
      quantified. RESULTS: Tongue and hypopharyngeal SCC cell lines were resistant to
      both TPA and PEP005, with the concentration required to inhibit growth by 50%
      (IC50) being >1,000 ng/ml. CAL-27 (tongue SCC) and FaDu (hypopharyngeal SCC) cell
      lines re-expressing PKCbetaI and -betaII isoforms demonstrated IC50 of 1-5 ng/ml
      with TPA or PEP005. CONCLUSION: Re-expression of PKCbeta in head and neck SCC
      cell lines leads to cells one thousand-times more sensitive to the cytotoxic
      effects of phorbol or diterpene esters in culture. This highlights the importance
      of the isoform in tumor progression and presents the potential benefit of these
      compounds in malignancies expressing the protein, and in combination therapy.

PMID- 25750278
TI  - Prognostic impact of blood biomarkers TS and DPD in neoadjuvant-treated
      esophageal cancer patients.
AB  - BACKGROUND/AIM: The prognostic value of TS (thymidylate synthase) and DPD
      (dihydropyrimidine dehydrogenase) RNA expression in the blood of patients with
      esophageal cancer is not known. The aim of the present study was to evaluate the
      significance of these molecular alterations in the blood as a prognostic marker
      for patients with neoadjuvant-treated esophageal cancer. PATIENTS AND METHODS: A
      total of 29 patients with locally advanced esophageal cancer (cT3-T4, Nx, M0)
      were enrolled in this prospective study. All patients received neoadjuvant
      chemoradiation followed by a transthoracic resection (curative transthoracic en
      bloc esophagectomy, RO). Peripheral blood samples were drawn before initiation of
      therapy. The analysis was performed using quantitative real-time-polymerase chain
      reaction (RT-PCR). The histomorphological regressions grading after neoadjuvant
      therapy was defined as follows: major response (MaR)=less than 10% vital tumor
      tissue, minor response (MiR)=more than 10% vital tumor tissue. RESULTS: Nineteen
      out of 29 patients (65.5%) had a MiR and 10 (34.5%) had a MaR. The median
      survival of patients was 2.08 years (range=0.15-4.53). Among the tested genes,
      the RNA expression of TS was significantly associated with prognosis of patients.
      Patients with TS expression above 0.78 had a median survival of 1.1 years
      (range=0.21-3.96) compared to 2.6 years (range=0.15 to 4.53) in patients with TS
      expression lower than 0.78 (p=0.031, log rank test). There was no association
      between clinical variables (e.g., tumor stage, gender, age, etc.) and the RNA
      expression of TS in the serum. CONCLUSION: The RNA expression of TS in the blood
      is a potential prognostic marker in patients with neoadjuvant-treated esophageal
      cancer. The significance of these molecular alterations as non-invasive
      prognostic marker for esophageal cancer should be evaluated in prospective
      studies.

PMID- 25750279
TI  - The protective effect of pyrimidine nucleosides on human HaCaT keratinocytes
      treated with 5-FU.
AB  - BACKGROUND: Therapy with 5-fluorouracil (5-FU) and capecitabine is often
      complicated by skin toxicity (hand-foot syndrome, HFS). Topical application of
      uridine ointment is beneficial for alleviating HFS and other pyrimidine
      nucleosides have been described as 5-FU toxicity modulators. We tested pyrimidine
      nucleosides and their combinations to find the best combination for topical
      therapy of HFS. MATERIALS AND METHODS: Cellular viability was measured by the
      real-time cell analyser and methyl thiazol tetrazolium (MTT) assay in order to
      evaluate the effect of pyrimidine nucleosides on HaCaT keratinocytes treated with
      5-FU. The results were confirmed by evaluation of the cellular colonization by
      microphotography. RESULTS: Cytidine and uridine protected keratinocytes to the
      same extent. Thymidine enhanced the protective effect when added to cytidine or
      uridine. Deoxycytidine did not have any protective effect. CONCLUSION: Our
      findings support the rationale for using uridine or cytidine in combination with
      thymidine in ointment for HFS treatment.

PMID- 25750280
TI  - Effect of anaesthetic technique on immune cell infiltration in breast cancer: a
      follow-up pilot analysis of a prospective, randomised, investigator-masked study.
AB  - BACKGROUND: Live animal studies using an inoculation model of breast cancer
      indicate that anaesthetic drugs and techniques differentially affect cancer
      metastasis, inversely related to Natural Killer (NK) cell and T lymphocyte
      levels. Clinical histological studies demonstrate that the distribution of these
      immune cells and macrophages in intra-tumoral cancer tissue can predict prognosis
      and response to therapy. No study has evaluated whether the anaesthetic technique
      influences human breast cancer immune cell infiltration. MATERIALS AND METHODS:
      Excised breast cancer specimens from patients previously enrolled in an ongoing,
      prospective, randomised trial (NCT00418457) investigating the effect of
      anaesthetic technique on long-term breast cancer outcome were
      immunohistochemically stained to enable a colour deconvolution technique to
      summate marked immune cell infiltration: CD56 (NK cells), CD4 (T helper cells),
      CD8 (T suppressor cells) and CD68 (macrophages). Patients were randomised to
      receive either a propofol-paravertebral anaesthetic with continuing analgesia
      (PPA, n=12) or a balanced general anaesthesia with opioid analgesia (GA, n=16)
      for 24 h postoperatively. Investigators were masked to group allocation. RESULTS:
      Normalised positive intensity values, (median (interquartile range (IQR)), for
      CD56 were lower in GA121 (116-134) versus 136 (132-142), p=0.015. CD4 was also
      lower in GA10.9 (5.5-27.8) versus PPA 19.7 (14.4-83.5), p=0.03 but CD8 5.5 (4.0
      9.75) versus 13.0 (5.0-14.5) respectively, p=0.24 and CD 68 infiltration 5.8
      (3.25-8.75) versus 8.0 (3.0-8.75), p=0.74 were not significantly different.
      CONCLUSION: PPA induces increased levels of NK and T helper cell infiltration
      into breast cancer tissue compared with GA but not T suppressor cells or macro
      phages. This is consistent with the hypothesis that the anaesthetic technique may
      affect perioperative immune function conducive to resisting breast cancer
      recurrence and metastasis.

PMID- 25750281
TI  - Expression of Sonic Hedgehog (SHH) in human lung cancer and the impact of
      YangZheng XiaoJi on SHH-mediated biological function of lung cancer cells and
      tumor growth.
AB  - Sonic Hedgehog (SHH) is a protein that is aberrantly expressed in various human
      tumors. SHH and its signaling molecules have been indicated as potential
      therapeutic targets. In the present study, we evaluated the expression of SHH
      transcript in human non-small cell lung cancer (NSCLC) tissues and investigated
      the impact of inhibiting SHH together with a traditional Chinese medicine
      formula, YangZheng XiaoJi (YZXJ), on the function and growth of lung cancer
      cells. Human NSCLC tissues had significantly higher levels of the SHH transcript
      compared matched normal lung tissues (n=83). TNM2 tumors and tumors with pleural
      invasion had higher levels than TNM1 and non-invasive tumors. High SHH levels
      were associated with a shorter overall survival (OS) of the patients. A SHH
      inhibitor, cyclopamine, and YZXJ alone or in combination had a marked inhibitory
      effect on cellular invasion and cellular migration of human lung cancer cells,
      A549 and SKMES1. YangZheng XiaoJi and its combination with cyclopamine also
      significantly reduced the growth of lung tumors in vivo together with a reduction
      of SHH and smoothened (Smo) proteins in the lung tumors. The present study
      provides evidence that blocking SHH by way of small inhibitor and by YangZheng
      XiaoJi has a profound influence on lung cancer cells as seen by in vitro invasion
      and cell migration and in vivo tumor growth. Together with the aberrant
      expression of SHH in NSCLC tumors in the patients, it is suggested that SHH is a
      potential target for therapies for NSCLC. 

PMID- 25750282
TI  - A metastatic hepatoma model of rats using the 13762-MAT-B-III cell line: basic
      characteristics and potential as a tool for interventional oncology experiments.
AB  - AIM: To evaluate the characteristics of a 13762-MAT-B-III model in the rat liver
      and to assess the adequacy of the model for transarterial embolization (TAE)
      study. MATERIALS AND METHODS: One hundred thousand 13762-MAT-B-III rat breast
      cancer cells were inoculated into the livers of 11 Fisher 344 rats. Natural
      course via magnetic resonance imaging (MRI) follow-up, histological
      characteristics and tumor response after TAE were evaluated. RESULTS: The tumor
      induction rate of the 13762-MAT-B-III hepatoma model was 100%. Except for one
      tumor that started to regress after 14 days, the 13762-MAT-B-III hepatomas showed
      rapid growth, up to 13.1+/-1.4 mm, at 21 days. Peritoneal seeding was observed in
      all rats. TAE was conducted successfully in three rats on day 11. The TAE-treated
      hepatomas were significantly smaller on day 21 (p=0.040) and had a significantly
      greater apoptosis ratio (p=0.046). CONCLUSION: The 13762-MAT-B-III hepatoma model
      can be useful in many interventional oncology studies by providing consistent and
      rapidly growing tumors.

PMID- 25750283
TI  - DNA damage in dihydroartemisinin-resistant Molt-4 cells.
AB  - Artemisinin generates carbon-based free radicals when it reacts with iron, and
      induces molecular damage and apoptosis. Its toxicity is more selective toward
      cancer cells because cancer cells contain a higher level of intracellular free
      iron. Dihydroartemisinin (DHA), an analog of artemisinin, has selective
      cytotoxicity toward Molt-4 human lymphoblastoid cells. A major concern is whether
      cancer cells could develop resistance to DHA, thus limiting its therapeutic
      efficacy. We have developed a DHA-resistant Molt-4 cell line (RTN) and found out
      that these cells exhibited resistance to DHA but no significant cross- resistance
      to artemisinin-tagged holotransferrin (ART-TF), a synthetic artemisinin compound.
      In the present study, we investigated DNA damage induced by DHA and ART-TF in
      both Molt-4 and RTN cells using the comet assay. RTN cells exhibited a
      significantly lower level of basal and X-ray-induced DNA damage compared to Molt
      4 cells. Both DHA and ART-TF induced DNA damage in Molt-4 cells, whereas DNA
      damage was induced in RTN cells by ART-TF, and not DHA. The result of this study
      shows that by the cell selection method, it is possible to generate a Molt-4 cell
      line which is not sensitive to DHA, but sensitive to ART-TF, as measured by DNA
      damage. 

PMID- 25750284
TI  - Interrogation of microRNAs involved in gastric cancer using 5p-arm and 3p-arm
      annotated microRNAs.
AB  - MicroRNAs are derived from endogenous stem-loop precursors, and play important
      roles in various biological processes. From next-generation sequencing data, it
      is suggested that both the 5p-arm and 3p-arm of mature miRNAs could be generated
      from a single miRNA hairpin precursor; however, the current miRNA databases fail
      to provide comprehensive arm annotation features, which could result in ambiguous
      and incomplete analyses. In the present report, we have annotated over 99.7% of
      miRNAs with the correct 5p-arm and 3p-arm features. The length distribution of
      all annotated miRNAs is around 22 nucleotides; however, the 5p-arm miRNAs seem to
      be longer than those of the 3p-arm, which is evident in the 23-nucleotide group.
      Our study effort generates comprehensive miRNA arm-feature annotation which can
      be utilized for better interrogation of miRNAs. In further analysis of human
      gastric cancer tissues, we identified 38 down-regulated miRNAs and 22 up
      regulated arm-specific miRNAs using this new comprehensives miRNA list. 

PMID- 25750285
TI  - Detection of peritoneal dissemination with near-infrared fluorescence
      laparoscopic imaging using a liposomal formulation of a synthesized indocyanine
      green liposomal derivative.
AB  - BACKGROUND/AIM: Although conventional staging laparoscopy (SL) has improved the
      diagnostic accuracy of peritoneal dissemination, novel technology is needed to
      increase the sensitivity of SL. We herein describe a new imaging method employing
      near-infrared (NIR) fluorescence imaging using a liposomal synthesized
      indocyanine green (ICG) liposomal derivative, LP-ICG-C18. METHODS AND RESULTS: LP
      ICG-C18 is a NIR-photoactivating probe in which an ICG fluorophore is covalently
      conjugated with a phospholipid moiety. Nude mice were intraperitoneally injected
      with gastric cancer cells. Twelve days later, the mice were given intravenous
      injections of LP-ICG-C18 at a dose of 0.15 mg/kg. A NIR imaging system was used
      to identify the disseminated tumors. The disseminated nodules in mice were
      detected without any difficulties. Disseminated tumor nodules were collected from
      mice with or without injections of liposomal formulation and were transferred
      into the swine peritoneal cavity. The nodules in the swine peritoneal cavity were
      clearly and promptly defined by the NIR imaging system. CONCLUSION: NIR
      fluorescing liposomal probes can effectively target peritoneal disseminated
      tumors and can be easily detected by a NIR imaging system. These results warrant
      future clinical trials of our imaging system and may contribute to a more precise
      diagnosis and therapeutic approach for gastric cancer patients.

PMID- 25750286
TI  - HVEM expression contributes to tumor progression and prognosis in human
      colorectal cancer.
AB  - BACKGROUND: Herpesvirus entry mediator (HVEM) has been recently suggested to play
      certain roles in cancer biology. We examined HVEM expression in human colorectal
      cancer (CRC) to reveal its clinical importance. MATERIALS AND METHODS:
      Immunohistochemical staining was carried-out in normal epithelium, benign and
      malignant lesions. RESULTS: While intense HVEM expression was not observed in
      normal epithelium and hyperplastic polyps, 24% of adenoma and more than half of
      CRCs had high HVEM expression. In 234 CRCs, HVEM expression was significantly
      associated with tumor status and pathological stage. Patients with high HVEM
      expression had a significantly poorer prognosis than those with low expression.
      Importantly, HVEM status had an independent prognostic value in CRC. Furthermore,
      HVEM status was inversely corrected with the presence of tumor-infiltrating T
      cells. CONCLUSION: HVEM may play a critical role in tumor progression and immune
      evasion, and may also be a novel prognostic marker and potential therapeutic
      target in human CRC.

PMID- 25750287
TI  - Flunarizine exhibits in vitro efficacy against lymphoma and multiple myeloma
      cells.
AB  - BACKGROUND/AIM: Novel agents such as lenalidomide and bortezomib have
      significantly improved today's therapy of multiple myeloma. Despite recent
      innovations, new therapeutic options are needed. The Wingless-related integration
      site (WNT) pathway is aberrantly activated in lymphoma and myeloma and therefore
      renders WNT signaling molecules attractive for the development of targeted
      therapies. Flunarizine was used in this study as it has chemical features similar
      to those of other known WNT inhibitors and already proven proapoptotic properties
      in leukemia cells. MATERIALS AND METHODS: The antitumor apoptotic effect of
      flunarizine at doses ranging from 0.1-200 MUM was investigated on three human
      lymphoma cell lines, one murine and four human myeloma cell lines by 3'3
      Dihexyloxacarbocyanine iodide and propidium iodide staining in flow cytometry.
      RESULTS: Flunarizine induced significant apoptotic activity in all tested myeloma
      and lymphoma cell lines in a dose-dependent manner. CONCLUSION: Our results
      reveal a significant selective induction of apoptosis by flunarizine and suggest
      an in vivo effect against lymphoma and myeloma.

PMID- 25750288
TI  - PCK3145 inhibits proliferation and induces apoptosis in breast and colon cancer
      cells.
AB  - AIM: To explore the effects of PCK3145 beyond prostate cancer. MATERIALS AND
      METHODS: Using Trypan blue, MTT proliferation assays, cell cycle and apoptosis
      analysis, we assessed the effects of PCK3145 on prostate (PC-3), breast (MCF-7)
      and colon (HT-29) human cancer cell lines and in osteosarcoma (MG-63) cells; any
      synergistic effects with docetaxel and oxaliplatin were also explored. RESULTS:
      PCK3145 inhibited proliferation and induced apoptosis of PC-3, MCF-7 and HT-29
      cells in a dose- and time-dependent manner but not in the MG-63 cell line,
      consistent with the low expression of the laminin receptor (LR) in the latter
      cell line. PCK3145 produced rapid (within 5 min) and transient (up to 60 min)
      activation of MEK and ERK1/2. Synergistic effects were observed with docetaxel
      and oxaliplatin. CONCLUSION: PCK3145 can exert anticancer activity not only on
      prostate but also on breast and colon cancer cells, possibly through LR-mediated
      activation of MEK and ERK1/2 phosphorylation.

PMID- 25750289
TI  - A long noncoding RNA, lncRNA-ATB, is involved in the progression and prognosis of
      colorectal cancer.
AB  - BACKGROUND/AIM: A long noncoding RNA (lncRNA) activated by transforming growth
      factor (TGF)-beta (lncRNA-ATB) was recently described to promote the invasion
      metastasis cascade in hepatocellular carcinoma. The aim of the present study was
      to clarify the clinicopathological role and prognostic relevance of lncRNA-ATB in
      colorectal cancer (CRC). MATERIALS AND METHODS: lncRNA-ATB expression was
      evaluated by real-time reverse transcription polymerase chain reaction in 124
      patients with CRC. Patients were divided into two groups based on the median
      lncRNA-ATB expression. RESULTS: High lncRNA-ATB expression was significantly
      associated with greater tumor size, depth of tumor invasion, lymphatic invasion,
      vascular invasion, and lymph node metastasis. Patients of the high-lncRNA-ATB
      expression group had significantly poorer outcomes than those of the low
      expression group. Additionally, levels of lncRNA-ATB expression were
      significantly higher in patients with hematogenous metastases. CONCLUSION: lncRNA
      ATB may be involved in the progression of CRC and be a novel indicator of poor
      prognosis in patients with CRC.

PMID- 25750290
TI  - Small molecules alter VEGFR and PTEN expression in HPV-positive and -negative
      SCC: new hope for targeted-therapy.
AB  - BACKGROUND/AIM: Prognosis for patients with head and neck squamous cell carcinoma
      (HNSCC) is poor in most cases and has not improved despite advances in therapy.
      Novel therapeutic approaches are mandatory in order to improve the situation.
      Everolimus, an inhibitor of mammalian target of rapamycin, as well as the multi
      tyrosine kinase inhibitors sorafenib and sunitinib, has demonstrated a
      substantial therapeutic effect in various types of human cancer with moderate
      side-effects. Expression of vascular endothelial growth factor receptor (VEGFR) 1
      and 2, and of the tumor-suppressor protein phosphatase and tensin homolog deleted
      on chromosome 10 (PTEN) were evaluated in chemonaive human papillomavirus (HPV)
      positive and -negative squamous cell carcinoma (SCC) and after exposure to
      everolimus, sorafenib or sunitinib. MATERIALS AND METHODS: p16-positive CERV196
      and p16-negative HNSCC 11A and 14C cells were incubated with different drug
      concentrations for 48-192 h. Expression of VEGFR1 and -2 as well as PTEN were
      determined by enzyme-linked immunosorbent assay and was compared to a chemonaive
      control. RESULTS: VEGFR1 and -2, as well as PTEN, were expressed in all three
      cell lines. Sunitinib, sorafenib and everolimus significantly reduced the
      expression of VEGFR1 and -2, especially in p16-positive CERV196 cells. Sunitinib
      appeared to be more effective in reducing VEGFR1 and -2 expression than sorafenib
      and everolimus. PTEN levels were remarkably lower in HPV-positive CERV196 cells.
      PTEN expression increased significantly under sunitinib and sorafenib in HNSCC
      11A and CERV196 cells. Everolimus, on the other hand, led to a significant
      decrease of PTEN expression in these cell lines. CONCLUSION: The tested drugs
      displayed a remarkable anti-angiogenic effect by inhibition of VEGFR1 and -2
      expression. Sunitinib and sorafenib were able to increase PTEN expression, which
      might induce apoptosis of cancer cells. HPV-positive CERV196 cells were
      characterized by an increased susceptibility to these small-molecule drugs.
      Further studies are imperative to scrutinize HPV status-dependent differences in
      drug response and possible implications for future treatment options.

PMID- 25750291
TI  - miR-200a, miR-200b and miR-429 are onco-miRs that target the PTEN gene in
      endometrioid endometrial carcinoma.
AB  - Endometrioid endometrial carcinoma (EEC) is a common malignancy of the female
      genital tract. However, no adequate biomarker is currently available for
      predicting the prognosis of this cancer. Recent studies have revealed
      dysregulated expression of several microRNAs (miRNAs) in various cancer tissues,
      and therefore, these cancer-associated miRNAs (also called onco-miRs) could be
      promising prognostic biomarkers of cancer progression or metastasis. In this
      study, in order to identify onco-miRs and their possible targets involved in EEC,
      we performed microarray-based integrative analyses of miRNA and mRNA expression
      in specimens excised from EEC lesions and adjacent normal endometrial tissues.
      Using integrated statistical analyses, we identified miR-200a, miR-200b and miR
      429 as highly up-regulated onco-miRs in EECs. Conversely, we detected expression
      of a tumor-suppressor gene, phosphatase and tensin homolog (PTEN), which was
      predicted in silico using a miRNA-targeting mRNA prediction algorithm, as a
      target of the three miRNAs and which was down-regulated in EECs. Furthermore,
      these miRNAs were validated to target PTEN experimentally using luciferase assays
      and real-time polymerase chain reaction. These results suggest that the
      occurrence of EEC is, at least in part, mediated by miRNA-induced suppression of
      PTEN expression. 

PMID- 25750292
TI  - Aberrant methylation of GCNT2 is tightly related to lymph node metastasis of
      primary CRC.
AB  - BACKGROUND: Glycoprotein expression profile is dramatically altered in human
      cancers; however, specific glycogenes have not been fully identified. MATERIALS
      AND METHODS: A comprehensive real-time polymerase chain reaction (PCR) system for
      glycogenes (CRPS-G) identified several outstanding glycogenes. GCNT2 was of
      particular interest after GCNT2 expression and epigenetics were rigorously
      investigated in primary colorectal cancer (CRC). RESULTS: The highlights of this
      work can be summarized as follows: (i) Expression of GCNT2 was remarkably
      suppressed. (ii) Silenced expression of GCNT2 was reactivated by combined
      demethylating agents. (iii) Promoter DNA methylation of GCNT2 was silenced in CRC
      cell lines and tissues. Hypomethylation of GCNT2 variant 2 is tightly associated
      with lymph node metastasis in primary CRC. (iv) GCNT2 methylation level in the
      normal tissues also showed a close association with that in the tumor tissues and
      reflected lymph node metastasis. CONCLUSION: We identified aberrant expression of
      GCNT2, which can be explained by promoter DNA hypermethylation. Hypomethylation
      of the GCNT2 variant 2 reflected lymph node metastasis of CRC in the tumor and
      normal tissues.

PMID- 25750294
TI  - beta-catenin Helices in the cytoplasm of sporadic and FAP duodenal adenomas.
AB  - BACKGROUND: Initiation and progression in conventional adenomas is triggered by
      deregulation of Wnt/beta-catenin signaling. In the absence of Wnt signal (off
      state), beta-catenin prevents phosphorylation of glycogen synthase kinase (GSK)
      3beta leading to aberrant nuclear accumulation in human tumors. While
      investigating the nuclear expression of beta-catenin in biopsies from duodenal
      adenomas, we observed a non-previously reported phenomenon, namely the presence
      of beta-catenin cytoplasmic helices (coils). MATERIALS AND METHODS: Sections from
      39 biopsies were immunostained with beta-catenin: 25 from duodenal adenomas and
      the remaining 14 had normal duodenal mucosa (n=11) or polypoid gastric duodenal
      metaplasia (n=3). RESULTS: Eighteen out of the 25 duodenal adenomas (72%) showed
      beta-catenin helices; in contrast, none of the 33 control biopsies (including
      those with normal duodenal mucosa, gastric duodenal metaplasia and normal mucosa
      adjacent to 19 adenomas) showed beta-catenin helices (p<0.05). The review of
      diagnostic H&E-stained sections and of beta-catenin-stained nuclei revealed that
      the dysplastic nuclei were arranged in a picket fence-like fashion along the
      basement membrane of the glands and not as loops within the dysplastic glands;
      the nuclei of the dysplastic glands were not forming part of the beta-catenin
      helices. DISCUSSION: If these beta-catenin coils are unrelated to an abnormal
      nuclear distribution at the base of the dysplastic glands, the rational
      explanation might be that the helices highlight changes taking place in the
      cytoplasm of affected glandular cells. CONCLUSION: According to some authors,
      mutations in the beta-catenin genes are always associated with a morphologically
      neoplastic course. It is herein proposed that beta-catenin helices in duodenal
      adenomas might uncover a novel cytoplasmic phenomenon ensuing during the adenoma
      carcinoma pathway.

PMID- 25750293
TI  - TSU-68 ameliorates hepatocellular carcinoma growth by inhibiting
      microenvironmental platelet-derived growth factor signaling.
AB  - BACKGROUND: TSU-68 is a multikinase inhibitor that targets platelet-derived
      growth factor receptors (PDGFRs). In the present study, we evaluated the effect
      of TSU-68 on the tumor-microenvironment interaction in hepatocellular carcinoma
      (HCC). MATERIALS AND METHODS: HCC and fibroblast cell lines (HuH7, Hep3B, HuH1
      and WI-38) were used to evaluate their interactions. Cancer characteristics were
      evaluated by spheroid formation and tumorigenicity in immunodeficient mice. Time
      lapse image analysis was performed to monitor cell motility. RESULTS: Although
      PDGFA was abundantly expressed, PDGFR-alpha was predominantly located in the
      cytoplasm and was not functional in HuH7 cells. Co-culture experiments
      demonstrated that HCC cells induced phosphorylation of PDGFR-alpha in WI-38
      fibroblasts and that stimulated fibroblasts, in turn, boosted the spheroid
      formation capacity of HCC cells. TSU-68 inhibited phosphorylation of PDGFR-alpha
      in WI-38 cells and suppressed the growth of subcutaneously co-injected HuH7/WI-38
      tumor xenografts. CONCLUSION: TSU-68 inhibits stromal PDGF signaling activated by
      cancer cells and suppresses HCC growth.

PMID- 25750295
TI  - Efficacy of combination chemotherapy using a novel oral chemotherapeutic agent,
      TAS-102, with irinotecan hydrochloride on human colorectal and gastric cancer
      xenografts.
AB  - TAS-102 is a novel oral nucleoside antitumor agent consisting of trifluridine and
      tipiracil hydrochloride at a molar ratio of 1:0.5. TAS-102 was approved in Japan
      in March 2014 for the treatment of patients with unresectable, advanced or
      recurrent colorectal cancer that is refractory to standard therapies. In the
      present study, enhancement of the therapeutic efficacy using a combination
      therapy of TAS-102 and irinotecan hydrochloride (CPT-11) was evaluated in a
      colorectal and gastric cancer xenograft-bearing nude mouse model. TAS-102 was
      orally administered twice a day from day 1 to 14, and CPT-11 was administered
      intravenously on days 1 and 8. The growth-inhibitory activity was evaluated based
      on the tumor volume and the growth-delay period, which was estimated based on the
      period required to reach a tumor volume that was five-times greater than the
      initial volume (RTV5). The tumor growth-inhibitory activity and the RTV5 of the
      group receiving TAS-102 with CPT-11 were significantly superior to those of both
      agents as monotherapy for mice with KM12C, KM12C/5-FU, DLD-1/5-FU, and SC-2
      xenografts (p<0.01). No significant decrease in body weight was observed. The
      present pre-clinical findings indicated that the combination of TAS-102 and CPT
      11 is a promising treatment option for colorectal or gastric cancer, not only for
      chemo-naive tumors, but also for recurrent tumors after 5-fluorouracil (5-FU)
      based chemotherapy. 

PMID- 25750296
TI  - MicroRNA-503 promotes tumor progression and acts as a novel biomarker for
      prognosis in oesophageal cancer.
AB  - AIM: This study investigated microRNA (miR)-503 expression levels and evaluated
      its clinical significance in patients with oesophageal cancer (EC). MATERIALS AND
      METHODS: miR-503 expression was quantified by quantitative reverse transcription
      polymerase chain reaction in 49 EC tissue samples and 12 adjacent normal tissues
      from 49 patients with EC. The association between miR-503 expression and
      clinicopathological factors, including prognostic outcomes, were assessed.
      RESULTS: miR-503 was found up-regulated in EC tissues compared to adjacent normal
      tissues. High miR-503 expression was significantly associated with large tumor
      size. Kaplan-Meier analysis showed that patients with high miR-503 expression had
      significantly poorer disease-free and overall survival than those with lower
      expression levels. High miR-503 expression was identified as an independent
      prognostic predictor in patients with EC according to multivariate analysis.
      CONCLUSION: miR-503 expression affects tumor cell proliferation in EC. Evaluation
      of miR-503 expression might thus help identify patients with EC with poor
      prognosis and higher risk of early recurrence.

PMID- 25750297
TI  - Antiproliferative activities of Fagara xanthoxyloides and Pseudocedrela kotschyi
      against prostate cancer cell lines.
AB  - BACKGROUND/AIM: Roots of Fagara zanthoxyloides and Pseudocedrela kotchyii are
      used as chewing sticks and as medicinal remedies for diarrhea, cough and fever in
      West Africa. Extracts of the two plants also possess anti-bacterial, anti-fungal
      and anti-malarial activities. The aim of the present study was to determine the
      effects of such extracts on the growth, proliferation and induction of apoptosis
      in four prostate cancer cell lines. Materials and Methods. Androgen-independent
      PC3 and DU-145 and androgen-dependent LNCaP and CWR-22 prostate cancer cell lines
      were cultured for five days with different concentrations of the extracts and
      examined for growth inhibition and evidence of apoptosis. RESULTS: Irrespective
      of their androgen dependence, all four cancer cell lines exhibited a dose
      dependent decrease in cell proliferation and viability by the 3-[4,5
      dimethylthiazol-2yl]-2,5-diphenyltetrazolium bromide (MTT) assay and in induction
      of apoptosis. The results also show that LNCap cells were the most sensitive to
      the two extracts, with highest inhibition at day 3 and exhibiting the highest
      rate of apoptosis. Conclusion. These observations suggest that F. zanthoxyloides
      and P. kotchyii could serve as potential chemopreventive agents in the treatment
      of prostate cancer.

PMID- 25750298
TI  - Phosphatidylserine-specific phospholipase A1 (PS-PLA1) expression in colorectal
      cancer correlates with tumor invasion and hematogenous metastasis.
AB  - BACKGROUND: The function of phosphatidylserine-specific phospholipase A1 (PS
      PLA1), a phospholipase that acts specifically on phosphatidylserine and produces
      lysophosphatidylserine, a lysophospholipid mediator, has not been fully
      elucidated. We evaluated the role of PS-PLA1 in oncogenesis and metastasis of
      colorectal cancer (CRC). MATERIALS AND METHODS: Specimens from 85 patients with
      CRC were immunostained with a monoclonal antibody against PS-PLA1. The
      correlation between PS-PLA1 expression and the clinicopathological variables was
      analyzed. RESULTS: Tumor depth and hematogenous metastasis independently
      positively correlated with PS-PLA1 expression. High PS-PLA1 expression was
      associated with shorter disease-free survival, although it was not an independent
      predictive factor. CONCLUSION: PS-PLA1 expression in CRC is associated with tumor
      invasion and metastasis.

PMID- 25750300
TI  - Sulfobetaine (dimethylsulfoniopropionate) and glycine betaine show incompatible
      involvement in crucial Ehrlich ascites carcinoma in mice.
AB  - BACKGROUND/AIM: The role of methylation reactions in cancer was examined using
      the methylating agents, sulfobetaine [dimethylsulfonioproponate (DMSP)], and
      glycine betaine (GB), in murine crucial Ehrlich ascites carcinoma (EAC) for up to
      10 days. RESULTS: DMSP administration in EAC-bearing mice mitigated EAC, while GB
      administration clearly promoted EAC. However, the immune cell profiles did not
      differ largely between animals receiving DMSP and those receiving GB. Moreover,
      DMSP and GB had merely any effects on proliferation of EAC cells in vitro.
      Injection of DMSP into normal mice interestingly led to macrophage accumulation
      in the peritoneal cavity in a dose-dependent manner at early rearing. CONCLUSION:
      These results indicate that GB promoted EAC by the methylation of cancer promotor
      gene, whereas DMSP ameliorated EAC by the accumulation of activated macrophages
      with a rapid response and long life span during cancer progression.

PMID- 25750299
TI  - Effects on DNA repair in human lymphocytes exposed to the food dye tartrazine
      yellow.
AB  - Tartrazine is a food additive that belongs to a class of artificial dyes and
      contains an azo group. Studies about its genotoxic, cytotoxic and mutagenic
      effects are controversial and, in some cases, unsatisfactory. This work evaluated
      the potential in vitro cytotoxicity, genotoxicity and effects on DNA repair of
      human lymphocytes exposed to the dye. We assessed the cytotoxicity of tartrazine
      by 3-(4,5-Dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide test and the
      response of DNA repair through comet assay (alkaline version). We used different
      concentrations of the dye, ranging from 0.25-64.0 mM. The results demonstrated
      that tartrazine has no cytotoxic effects. However, this dye had a significant
      genotoxic effect at all concentrations tested. Although most of the damage was
      amenable to repair, some damage remained higher than positive control after 24 h
      of repair. These data demonstrate that tartrazine may be harmful to health and
      its prolonged use could trigger carcinogenesis. 

PMID- 25750301
TI  - Chemotherapy-induced changes and immunosenescence of CD8+ T-cells in patients
      with breast cancer.
AB  - BACKGROUND: Changes in sub-populations of cytotoxic (CD8+) T-cells, which are
      observed in aging and in conditions of chronic immune stimulation, are not well
      documented in cancer. MATERIALS AND METHODS: Using flow cytometry, CD8+ T-cell
      subsets were analyzed in patients with breast cancer undergoing DNA-damaging
      chemotherapy and in an older female control group during a six-month longitudinal
      study, to explore shifts in CD8+ T-cells and the effect of DNA-damaging
      chemotherapy on different T-cell sub-populations. RESULTS: As expected, there was
      a consistent decrease in absolute numbers of leukocytes, lymphocytes, T-cells and
      CD8+ T-cells during chemotherapy in patients with cancer. Among the T-cells,
      there was a lower CD8-/CD8+ ratio, persisting over the six months, in patients
      with cancer compared to controls. The proportion of CD28-CD57+ cells also
      remained higher among patients with cancer throughout the sampling duration. The
      number of CD28+CD57- and CD28-CD5- cells decreased faster during DNA-damaging
      chemotherapy than CD28+CD57+ and CD28-CD57+ cells, while only CD28-CD57- cells
      showed a significant reconstitutive capacity after six months. CONCLUSION:
      Immunosenescence appeared to be pronounced in patients with breast cancer, with
      senescent CD8+ T-cells playing a role. The normal condition was not restored
      after six months of chemotherapy.

PMID- 25750302
TI  - Anticancer effect of a novel palladium-saccharinate complex of terpyridine by
      inducing apoptosis on Ehrlich ascites carcinoma (EAC) in Balb-C mice.
AB  - BACKGROUND/AIM: [Pd(sac)(terpy)](sac)*4H2O (sac=saccharinate and terpy=2,2':6',2"
      terpyridine) is newly-synthesized palladium(II) (Pd) complex. We investigated the
      antiproliferative and apoptotic effects of this complex on Ehrlich ascites
      carcinoma (EAC). MATERIALS AND METHODS: EAC cells were administered to 33 Balb/c
      mice. Mice were divided randomly into four groups: control, cisplatin, Pd(II)
      complex and paclitaxel. Control group animals received 0.9% NaCl; other groups
      received treatments cisplatin, Pd(II) complex and paclitaxel on days 7 and 12. At
      day 14, animals were sacrificed. Expression of active caspase-3, p53 and
      proliferating cell nuclear antigen (PCNA) was investigated and apoptosis was
      evaluated by terminal deoxynucleotidyltransferase (TdT)-mediated nick-end
      labelling (TUNEL) technique. RESULTS: Expression of p53 and PCNA were found to be
      decreased (p<0.0001), cells with active caspase-3 and TUNEL-positive cells were
      found to be increased (p<0.0001) in all treatment groups. CONCLUSION: Like
      cisplatin and paclitaxel, this Pd(II) complex has a strong anticancer activity
      against EAC by inducing apoptosis and suppressing proliferation in vivo.

PMID- 25750303
TI  - Supernatants of tumours treated with chemotherapy can alter tumour growth and
      development in vivo.
AB  - BACKGROUND: Tumour-derived supernatants are comprised of bioactive substances
      that have the capacity to transform host systems rendering them more supportive
      of tumour growth. Certain chemotherapies are able to alter the make-up of these
      supernatants. MATERIALS AND METHODS: We explored the effects that vaccination
      with supernatants derived from tumours may have on tumour growth in a BALB/c
      model. RESULTS: A number of cytokines were detected in the supernatants capable
      of increasing B-cell lymphoma 2 (BCL2) protein expression in cancer cells; of
      note, significantly higher levels of granulocyte-macrophage colony stimulating
      factor (GM-CSF) were detected in chemotherapy-treated supernatants compared to
      controls. Vaccinating mice with supernatants from untreated tumours significantly
      impeded the growth of sub-cutaneous-implanted tumours. However, this anticancer
      effect was significantly diminished if the supernatants used were from cancer
      cells treated with gemcitabine. CONCLUSION: The study lends in vivo support to
      the idea that tumours produce bioactive components that can influence host
      biology and that certain chemotherapies can negate these.

PMID- 25750304
TI  - Elimination of Ras Suppressor-1 from hepatocellular carcinoma cells hinders their
      in vitro metastatic properties.
AB  - BACKGROUND/AIM: Extracellular matrix (ECM) is of great significance for
      homeostasis in the liver. In fact, one of the stages leading to hepatocellular
      carcinoma (HCC) includes accumulation of excess ECM. Ras Suppressor-1 (RSU-1) is
      localized in the cell-ECM adhesions but its role in HCC is unexplored. MATERIALS
      AND METHODS: We investigated the expression and role of RSU-1 in two HCC cell
      lines that differ in aggressiveness; non-invasive Alexander cells and highly
      invasive HepG2 cells. RESULTS: Our results showed that RSU-1 expression is
      elevated in HepG2 cells both at the mRNA and protein level, while its silencing
      leads to increased cell proliferation in both cell lines. Interestingly, RSU-1
      depletion from highly invasive HepG2 cells reduces cell adhesion and invasion.
      CONCLUSION: This is the first study to provide in vitro evidence for the
      involvement of RSU-1 in HCC cell invasive behavior.

PMID- 25750305
TI  - Expression of immunohistochemical markers of progression in pre-cancerous and
      cancerous human colon: correlation with serum vitamin D levels.
AB  - BACKGROUND/AIM: We aimed to evaluate vitamin D levels in blood, as well as the
      immunohistological expression of beta-catenin, p21 activated kinase (PAK1), p53
      and Ki67 in relation to histological type and grading of colonic tumors. RESULTS
      were compared to the expression in normal and adenomatous colon. MATERIALS AND
      METHODS: We analyzed colorectal specimens from 20 patients with colorectal tumors
      for expression of beta-catenin, PAK1, p53 and Ki67. Associations between the
      expression of these markers and levels of vitamin D in serum were analyzed.
      RESULTS: The average 25-hydroxy-vitamin D (25OHD) level in a healthy population
      was 20.53 ng/ml, while that in patients with colorectal cancer was 5.99 ng/ml.
      The average vitamin D level in patients with positive nuclear beta-catenin was
      4.58 ng/ml, which was lower than that of patients with negative nuclear beta
      catenin expression. Patients with positive nuclear PAK1 also had low vitamin D
      levels in their blood (4.51 ng/ml). Patients with positive nuclear p53 had
      significantly lower vitamin D levels (4.18 ng/ml), compared to patients without
      nuclear p53 expression. In patients with Ki67 expression in at least 50% of
      cells, the average vitamin D level was 6.27 ng/ml, while in patients with Ki67
      staining in fewer than 50% of cells, the average vitamin D levels in serum was
      double (13.42 ng/ml).

PMID- 25750306
TI  - APOBEC3B: a potential factor suppressing growth of human hepatocellular carcinoma
      cells.
AB  - BACKGROUND: To realize the role of apolipoprotein B mRNA editing enzyme,
      catalytic polypeptide-like 3B (APOBEC3B) in hepatocellular carcinoma (HCC)
      occurrence, mRNAs of APOBEC3B from tumor and non-tumor tissues of patients with
      hepatectomy were isolated and in vitro studies were designed. MATERIALS AND
      METHODS: Seventy-two tumor and non-tumor tissue samples, as well as clinical
      data, were collected from HCC patients during hepatectomy. The mRNA of APOBEC3B
      was assessed by real-time polymerase chain reaction. The viability of pLV
      APOBEC3B-transfected Hep 3B cells was then determined. Cell growth of pLV
      APOBEC3B-transfected Hep 3B cells was evaluated by in vitro migration assay.
      RESULTS: The real-time polymerase chain reaction results indicated a higher
      expression of APOBEC3B mRNA in tumor tissues than in non-tumor tissues of
      patients with HBsAg+ HCC. The expression of APOBEC3B in tumor or non-tumor tissue
      was not found to be a risk factor of recurrence in patients with HCC. The cell
      viability assay results indicated the growth-inhibitory effects of APOBEC3B on
      Hep 3B cells. The cell migration results indicated that APOBEC3B inhibits wound
      healing in Hep 3B cells. CONCLUSION: Based on these observations, we infer that
      APOBEC3B is a potential factor contributing to suppression of tumor growth in
      HCC.

PMID- 25750307
TI  - Predominance of Th17 over regulatory T-cells in pleural effusions of patients
      with lung cancer implicates a proinflammatory profile.
AB  - BACKGROUND: Regulatory T-(Treg) and pro-inflammatory T-helper 17 (Th17) cells
      have been reported to be involved in the pathogenesis of pleural effusions caused
      by lung cancer. However, the presence of these subsets might not be a consequence
      of tumor pathogenesis, but rather a result of the pleural effusion itself,
      irrespective of its origin. In the present study, we analyzed the balance between
      these CD4+ T-cell subsets and compared them with those in non-malignant pleural
      effusions. PATIENTS AND METHODS: We detected the frequencies of Treg and Th17
      cells, identified as cluster of differentiation (CD)3+CD4+CD25+CD127low/- and
      CD3+CD4+ retinoid-related orphan receptor gammat (RORgammat)+ cells respectively,
      and proportions of interleukin (IL)17A-producing CD4+ cells in pleural effusions
      of patients with lung cancer, tuberculous and non-chronic pathologies by flow
      cytometry. The cytokine profile of stimulated CD4+ T-cells from tuberculosis and
      cancer groups was compared. RESULTS: The proportion of Th17 cells were increased
      whereas Tregs were decreased in both tuberculosis and cancer, but not in non
      chronic pathologies. Nevertheless, CD4+ T-cells from lung cancer effusions
      secreted interferon (IFN)gamma, IL6 and IL17A, whereas CD4+ T-cells from
      tuberculous effusions secreted IL10 and low levels of IFNgamma. CONCLUSION:
      Although effusions from patients with chronic pathologies presented higher
      proportions of Th17 cells in comparison to those with non-chronic pathologies,
      only Th17 cells from malignant effusions maintained their proinflammatory profile
      after stimulation. Thus, in the pleural compartment of patients with lung cancer,
      a proinflammatory environment might be favored and possibly maintained by Th17
      response.

PMID- 25750308
TI  - AKT/mTOR down-regulation by CX-4945, a CK2 inhibitor, promotes apoptosis in
      chemorefractory non-small cell lung cancer cells.
AB  - AIM: The response to chemotherapeutic drugs in non-small cell lung cancer (NSCLC)
      is unsatisfactory, leading to poor outcomes. This study the aimed to investigates
      anticancer effects of CX-4945, a potent casein kinase II (CK2) inhibitor, in
      chemorefractory NSCLC cells. MATERIALS AND METHODS: Cell proliferation and
      apoptosis assay were carried-out by annexin V-FITC and FACScan after drug
      treatment with paclitaxel, cisplatin and CX-4945. AKT/mTOR and CK2alpha signals
      were measured by western blotting. Treatment was carried-out using siRNA to
      inhibit CK2alpha. RESULTS: Paclitaxel, and cisplatin effectively inhibited cell
      proliferation and induced apoptosis in A549 cells, while not in H1299, Calu-1 and
      H358 cells. In these chemorefractory cell lines, AKT signalling was maintained
      despite drug treatment. However, CX-4945 suppressed cell growth, with cell-cycle
      arrest at G2/M phase and induced apoptosis with an increase of cleaved caspase-3
      and PARP1 in a dose-dependent manner. Accordingly, AKT and its downstream signals
      such as mTOR and p70S6K were down-regulated by CX-4945. Transfection of CK2alpha
      siRNA had similar effects to CX-4945 treatment on cell proliferation and
      apoptosis. CONCLUSION: CX-4945 shows a promising anticancer action through down
      regulation of AKT/mTOR signals, suggesting its possible application for treatment
      of chemorefractory lung cancer.

PMID- 25750309
TI  - In vitro exposure of NK-92 cells to serum from patients with non-small cell lung
      cancer impairs their cytotoxicity.
AB  - AIM: To investigate the effect of serum from patients with non-small cell lung
      cancer (NSCLC) on in vitro cytotoxicity of the clonal cell line NK-92. MATERIALS
      AND METHODS: Twenty-six patients with NSCLC were included in this study. NK-92
      cells were incubated in medium supplemented with 25% of each patient's serum
      (before and after chemotherapy) for 24 h, then washed and tested for cytotoxicity
      against NK-sensitive K562 targets. RESULTS: The cytotoxicity of NK-92 cells
      exposed to serum from patients with NSCLC before chemotherapy initiation was
      significantly reduced compared to that upon incubated with serum from healthy
      individuals (p<0.001). NK-92 cytotoxicity was further reduced upon exposure to
      patient's serum after the first and third chemo therapy cycles (p<0.001).
      CONCLUSION: The results of our in vitro study suggest that serum of patients with
      NSCLC may exert per se an inhibitory effect on the cytotoxicity of NK-92 cells
      and this negative regulation may be enhanced with chemotherapy.

PMID- 25750311
TI  - The concurrent use of aromatase inhibitors and radiotherapy induces
      echocardiographic changes in patients with breast cancer.
AB  - AIM: Adjuvant radiotherapy (RT) for left-sided breast cancer has a negative
      impact on cardiac health. The concurrent use of aromatase inhibitors (AIs) during
      RT was found to increase the anticancer efficacy of radiation in pre-clinical
      models. We evaluated whether the acute effects of RT on cardiac functions are
      augmented by the concurrent use of AIs. PATIENTS AND METHODS: Sixty patients with
      early-stage left-sided breast cancer underwent a 2D echocardiography,
      electrocardiogram and cardiac biomarker measurements before and after adjuvant
      breast RT. Data were analyzed in two groups according to AI use. RESULTS: We
      observed a significant (p<0.05) decrease in right ventricular systolic function
      during RT in tricuspid annular plane systolic excursion (TAPSE). TAPSE decreased
      by 3.0 mm [95% confidence interval (CI)=1.9-4.1 mm] in the AI group and 1.4 mm
      (95% CI=0.3-2.4 mm) in the non-AI group. In addition, left ventricular diastolic
      function decreased among patients using AI, as the mitral inflow E-wave decreased
      5.8 cm/s (95% CI=1.8-9.7 cm/s) (p=0.006). CONCLUSION: The concurrent use of AI
      during RT for left-sided breast cancer led to a more pronounced change on right
      ventricular systolic function and left ventricular diastolic functions compared
      to RT alone.

PMID- 25750310
TI  - Vitamin D receptor genetic polymorphisms are associated with PSA level, Gleason
      score and prostate cancer risk in African-American men.
AB  - BACKGROUND/AIM: Several studies have revealed an association between single
      nucleotide polymorphisms (SNPs) in the VDR gene and prostate cancer (PCa) risk in
      European and Asian populations. To investigate whether VDR SNPs are associated
      with PCa risk in African-American (AA) men, nine VDR SNPs were analyzed in a case
      control study. MATERIALS AND METHODS: Multiple and binary logistic regression
      models were applied to analyze the clinical and genotypic data. RESULTS: rs731236
      and rs7975232 were significantly associated with PCa risk (p<0.05). In the
      analysis of clinical phenotypes, rs731236, rs1544410 and rs3782905 were strongly
      associated with high PSA level (p<0.05), whereas rs1544410 and rs2239185 showed a
      statistically significant association with high Gleason score (p<0.05). Haplotype
      analysis revealed several VDR haplotypes associated with PCa risk. Additionally,
      a trend existed, where as the number of risk alleles increased in the haplotype,
      the greater was the association with risk (p-trend=0.01). CONCLUSION: These
      results suggest that the VDR SNPs may be associated with PCa risk and other
      clinical phenotypes of PCa in AA men.

PMID- 25750312
TI  - Phase I study of everolimus, cetuximab and irinotecan as second-line therapy in
      metastatic colorectal cancer.
AB  - AIM: To evaluate feasible doses of weekly everolimus and irinotecan given with
      cetuximab for previously treated metastatic colorectal cancer (mCRC). PATIENTS
      AND METHODS: Adults with mCRC that progressed after 5-fluorouracil or
      capecitabine-plus-oxaliplatin were treated using a sequential dose escalation
      scheme. Dosing decisions were based on the probability of experiencing a dose
      limiting toxicity (DLT) during the first two 21-day treatment cycles. RESULTS:
      Patients received everolimus 30 mg/week plus irinotecan 350 mg/m2 q3w (n=5; dose
      A1) or everolimus 30 mg/week plus irinotecan 250 mg/m2 q3w (n=14; dose B1). Among
      patients evaluable for the maximum tolerated dose, two out of four in A1 and one
      out of eight in B1 experienced four DLTs. The trial was terminated early based on
      changes in clinical practice and emerging data on everolimus dosing. CONCLUSION:
      The feasible doses of everolimus and irinotecan administered with cetuximab as
      second-line therapy in mCRC were 30 mg/week and 250 mg/m2, respectively.

PMID- 25750313
TI  - Matched-pair analysis of dendritic cell versus targeted-therapy in patients with
      metastatic renal cell carcinoma.
AB  - BACKGROUND/AIM: Although targeted-therapy (TT) for patients with metastatic renal
      cell cancer (mRCC) has shown an improved outcome, their prognosis is still very
      poor. Immunotherapy with dendritic cells (DC) as one promising new treatment
      tries to fight cancer by boosting the patient's own immune system. The present
      analysis matches two different methods of treatment against mRCC, namely
      sequential TT versus DC vaccine therapy, by comparison of long-term overall
      survival (OS). PATIENTS AND METHODS: Data of patients treated with DC vaccines
      (N=30) in three clinical phase I/II trials (1999-2003) and patients treated with
      clinical standard targeted-therapy (N=30) at the University Hospital of Bonn
      (2010-2013) were analyzed regarding their OS, as well as specific characteristics
      such as number and localization of metastatic sites. RESULTS: The mean OS from
      the first treatment was significantly higher in the TT than in the DC group (48
      versus 21 months, range=3-85 months versus 1-57 months, respectively; p=0.0002).
      Patients with one (p=0.036) or two metastases (p=0.037) and especially patients
      with bone metastases (52 versus 12 months; p<0.0001) benefited significantly from
      TT. However, there was no significant difference between therapy types in
      patients with lung (p=0.147) or liver (p=0.745) metastases, or in patients with
      more than two metastatic sites (p=0.074). CONCLUSION: Targeted therapy is an
      effective treatment against mRCC, but is limited due to common adverse events and
      a higher toxicity when combinations of different-targeted agents are used.
      Immunotherapy with DC vaccines seems to be a potent and well-tolerated therapy
      against mRCC, possibly showing higher benefit for patients with specific sites of
      metastasis, and should be investigated as a co-treatment with TT in further
      studies.

PMID- 25750314
TI  - Hybrid-including endoscopic versus open hepatic resection for patients with
      hepatocellular carcinoma meeting the Milan criteria: a propensity case-matched
      analysis.
AB  - AIM: To clarify the surgical outcome of patients who underwent endoscopic
      hepatectomy (EH) compared to those of conventional open hepatectomy (OH) for
      hepatocellular carcinoma (HCC). PATIENTS AND METHODS: Between 1999 and 2011, 269
      HCC patients meeting the Milan criteria were divided into EH (n=89) and OH groups
      (n=180). To equalize the background covariates, a one-to-one propensity case
      matched analysis was used. RESULTS: With propensity matching, 52 EH and 52 OH
      patients showed comparable preoperative clinical characteristics. The operation
      time (320 min, p=0.049) and the median blood loss (180 g, p<0.001) was
      significantly lesser with EH, while the median postoperative hospital stay (11
      days, p=0.002) was significantly shorter for EH. The cumulative disease-free and
      overall survival rates were equivalent in both groups. CONCLUSION: EH for HCC
      patients meeting the Milan criteria is less invasive and might provide an
      equivalent disease-free and overall survival when compared to conventional OH.

PMID- 25750315
TI  - Surgery at primary versus relapsed epithelial ovarian cancer: a study on aspects
      of anaesthesiological management.
AB  - BACKGROUND: Primary cytoreductive surgery (CS) for epithelial ovarian cancer
      (EOC) is well-established. CS at relapse remains controversial, with an unclear
      morbidity profile. PATIENTS AND METHODS: We analyzed 121 patients with EOC who
      underwent CS. Two groups were identified by timing of surgery due to primary
      disease and due to recurrent disease. RESULTS: CS for primary versus recurrent
      EOC led to no differences in haemodynamic management, such as transfusion rates,
      application of vasopressors, ICU and hospital length of stay, or mortality. The
      risk for postoperative ileus was higher in patients with relapsed versus primary
      EOC. This might be attributed to patients being operated due to preoperative
      ileus and a higher small bowel resection rate at CS for relapse. CONCLUSION: CS
      for EOC relapse does not seem to be more challenging in terms of perioperative
      management compared to that at initial diagnosis. The major surgical morbidity
      profile was comparable apart from a higher risk for postoperative ileus at
      relapse.

PMID- 25750316
TI  - Efficacy of tegafur-uracil in advanced urothelial cancer patients after the
      treatment failure of platinum-based chemotherapy.
AB  - BACKGROUND: Platinum-based chemotherapy is the first-line treatment for advanced
      urinary tract urothelial cancers. However, the optimal second-line treatment is
      unclear. Although tegafur-uracil is sometimes used for advanced urothelial cancer
      patients after the treatment failure of platinum-based chemotherapy, there is
      little evidence regarding its use as a second-line treatment. PATIENTS AND
      METHODS: Advanced urothelial cancer patients previously treated with platinum
      based chemotherapy were retrospectively analyzed. Overall survival (OS) was
      compared between patients with and without tegafur-uracil treatment. RESULTS:
      Thirty-one patients (27 and 4 patients with and without tegafur-uracil treatment,
      respectively) were analyzed. OS from the last day of the final chemotherapy
      course was better in patients with tegafur-uracil treatment than in those without
      (p<0.001, 358 and 66.5 days of the median survival time, respectively).
      CONCLUSION: Tegafur-uracil may be a candidate for the secondary treatment of
      advanced urothelial cancer patients after the treatment failure of platinum-based
      chemotherapy.

PMID- 25750317
TI  - A case of endobronchial NUT midline carcinoma with intraluminal growth.
AB  - BACKGROUND: NUT midline carcinoma (NMC) is a rare, lethal form of differentiated
      squamous cell carcinoma characterized by chromosomal rearrangement of the NUT
      gene. Its highly aggressive nature commonly leads to unresectable and metastatic
      lesions. CASE REPORT: We report on a case of endobronchial NMC in a middle-aged
      man who was treated by bronchoscopic electrocautery followed by Ewing sarcoma
      based chemotherapy with concurrent chemoradiotherapy. The patient's disease
      continued to be stable 31 months after diagnosis. REVIEW: NMC is a challenging
      disease entity, which is difficult to diagnose and treat, and has a dismal
      overall survival. Most cases of NMC are widely metastatic or unresectable when
      diagnosed. DISCUSSION: This is the first reported case that involves intraluminal
      tumour growth of NMC and demonstrates the effectiveness of early intensive local
      therapy aided by bronchoscopic techniques.

PMID- 25750318
TI  - Pancreatoduodenectomy en bloc with portal and superior mesenteric artery
      resection--a case report and literature review.
AB  - BACKGROUND: Pancreatic cancer is one of the most lethal malignancies and is
      associated with a very poor overall survival. However, it seems that the only
      curative option remains an aggressive surgical approach capable of obtaining a
      radical resection. Unfortunately, this desiderate is even harder to be obtained
      when it comes to pancreatic tumors with vascular invasion. CASE REPORT: We
      present the case of a 65-year-old patient who was diagnosed with a
      cephalopancreatic tumor invading both the portal vein and the superior mesenteric
      artery. RESULTS: Whipple procedure was performed with portal and superior
      mesenteric artery resection; the continuity of the portal vein was established by
      an end-to-end anastomosis, while the superior mesenteric artery was re-implanted
      in the infra-renal aorta. CONCLUSION: Due to improvements of surgical techniques
      and postoperative management, the postoperative morbidity and early mortality
      significantly decreased and enabled the surgeon to perform ultra-radical surgery
      with better outcome.

PMID- 25750319
TI  - Long-term platinum retention after platinum-based chemotherapy in testicular
      cancer survivors: a 20-year follow-up study.
AB  - AIM: Evaluation of long-term platinum (Pt) retention in testicular cancer
      survivors (TCSs) treated with platinum-based chemotherapy to elucidate possible
      mechanisms of developing late effects. PATIENTS AND METHODS: 458 TCSs treated
      1980-1994 participated in a national follow-up study (2007-2008). Four treatment
      groups were evaluated for long-term serum Pt levels: surgery (n=135), cumulative
      cisplatin<=850 mg (n=252), cisplatin>850 mg (n=57) and carboplatin (n=14).
      RESULTS: The median observation time was 20 (range=13-28) years. The median Pt
      level according to treatment group was: surgery, 50 ng/l; cisplatin<=850 mg, 85
      ng/l; cisplatin>850 mg, 106 ng/l; carboplatin, 40 ng/l. The risk for having a Pt
      level in the highest quartile was positively associated with cisplatin dose
      (Ordinal regression (OR)=1.29, per 100 mg increase in cisplatin dose, 95%
      Confidence interval (CI)=1.20-1.38), and negatively associated with follow-up
      time (OR=0.50 per 5-year increase in follow-up time, 95% CI=0.37-0.68).
      CONCLUSION: Pt levels are significantly elevated in serum at a median of 20 years
      after cisplatin-based chemotherapy for testicular cancer.

PMID- 25750320
TI  - Emotional personality/proximity versus emotional authenticity in patient
      physician communication in healthy study participants, and in patients with
      benign breast disease, and breast cancer: a prospective case-control study in
      Finland.
AB  - BACKGROUND/AIM: The associations between emotional personality, proximity and
      authenticity in patient-physician communication during breast cancer (BC)
      consultations are rarely considered together in a prospective study. We,
      therefore, investigated emotional personality/proximity versus authenticity in
      patient-physician communication in healthy study subjects (HSS) and in patients
      with benign breast disease (BBD) and breast cancer (BC). PATIENTS AND METHODS: In
      the Kuopio Breast Cancer Study, 115 women with breast symptoms were evaluated
      regarding emotional personality, proximity and authenticity in their a patient
      physician communication before any diagnostic procedures were carried-out.
      RESULTS: The emotional personality and the emotional proximity in patient
      physician communication was highly significantly positively correlated in the BBD
      group. The kappa-values for emotional personality versus emotional proximity in
      the HSS, BBD and BC groups were statistically significant. There was also a
      highly significant positive correlation between emotional personality and
      emotional authenticity in the HSS, BBD and BC groups and the kappa values in the
      HSS, BBD and BC groups were statistically significant. There was a highly
      significant positive correlation between emotional proximity and emotional
      authenticity in the BBD group, and the weighted kappa-values in the BBD group
      were statistically significant. CONCLUSION: The results of the present study
      support a powerful link between emotional personality/proximity and emotional
      authenticity, and provides new information in patient-physician communication in
      the HSS, BBD and BC groups. This finding is of clinical importance, since during
      breast disease consultation, barriers to patient-physician communication may be
      associated with difficulties in early BC diagnosis in the breast cancer
      diagnostic unit.

PMID- 25750321
TI  - The impact of thyroid nodule size on the risk of malignancy in follicular
      neoplasms.
AB  - BACKGROUND/AIM: Studies have shown that the risk of malignancy in follicular
      neoplasms is as high as 30%. Often, surgery is recommended for such lesions, not
      for therapeutic purposes but as a diagnostic method, leading to increased
      hospital costs and related morbidities. Recent studies have suggested that tumor
      size predicts malignant potential of these follicular neoplasms. Our aim was to
      identify the impact of nodule size on the risk of malignancy for such lesions.
      PATIENTS AND METHODS: A retrospective medical chart review was undertaken for
      patients who underwent thyroid surgery at a single academic North American
      Institution. A total of 120 follicular lesions, follicular neoplasms (Bethesda
      category IV) or follicular lesions of undetermined significance (Bethesda
      category III) in 110 patients undergoing thyroid surgery were evaluated. Nodule
      size as measured by ultrasound, fine-needle aspiration cytological results, and
      final histopathology reports were reviewed. Analysis was performed by
      classification according to nodule size: <3 cm, >=3 cm, <4 cm and >=4 cm.
      RESULTS: Out of the 120 nodules, 48 (40%) were reported to be malignant on final
      pathological examination. The malignancy rate in nodules<3 cm and >= 3cm was 41%
      and 37.8%, respectively (p=0.84). When 4 cm was used as the cut-off, the rate in
      nodules<4 cm and >=4 cm was 40.6% and 37.5%, respectively (p=0.82). CONCLUSION:
      Increased thyroid nodule size does not increase the malignancy rate for
      follicular neoplasms. Hence, we recommend against routine total thyroidectomy for
      patients with follicular neoplasms based on the size criteria.

PMID- 25750322
TI  - Aberrant P53 expression lacks prognostic or predictive significance in colorectal
      cancer: results from the VICTOR trial.
AB  - AIM: Biomarkers with prognostic and predictive value can help stratify patients
      with colorectal cancer (CRC) into appropriate treatment groups. We sought to
      evaluate the clinical utility of P53 protein expression as a biomarker in VICTOR,
      a large phase III trial of rofecoxib in stage II and III CRC. PATIENTS AND
      METHODS: Tissue micro arrays were constructed from 884 tumors and the expression
      of P53 was examined by immunohistochemistry. Tumors were dichotomised as either
      P53-positive (nuclear expression in >10% of cells or the 'absent' pattern, both
      representing TP53 mutation) or P53-negative (nuclear expression in <10% of
      cells). RESULTS: Aberrant P53 expression was found in 65% (482/740) of patients.
      It was associated with distal location (p<0.001) and stage III disease (p<0.001).
      No effect was observed on disease-free or overall survival, and there was no
      interaction with chemotherapy or radiotherapy. CONCLUSION: Analysis of P53
      expression in the patients recruited to the VICTOR trial confirmed that P53
      expression is associated with site and stage of CRC. However, independently, this
      biomarker has neither prognostic nor predictive utility in this cohort of
      patients.

PMID- 25750323
TI  - Antiviral therapy and long-term outcome for hepatitis B virus-related
      hepatocellular carcinoma after curative liver resection in a Japanese cohort.
AB  - AIM: The aim of this study was to determine whether antiviral therapy with
      nucleotide/nucleoside analog (NA) is beneficial for Japanese patients with
      hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) who underwent
      initial curative liver resection. PATIENTS AND METHODS: In 162 patients with
      positive hepatitis B surface antigen and negative anti-hepatitis C virus
      antibody, sixty-two patients received antiviral therapy with NA (NA group) and
      the remaining 100 patients did not (non-NA group). Prognostic factors for disease
      free survival (DFS) and overall survival (OS) were evaluated. Moreover, to
      equalize the background covariates, a one-to-one propensity case-matched analysis
      was used. RESULTS: NA administered were lamivudine (LAM) solely for 21 patients,
      LAM plus adefovir dipivoxil (ADV) for 6, LAM switched to entecavir (ETV) for 5
      and ETV solely for 31. DFS did not significantly differ between the NA group and
      non-NA group (p=0.19). However, OS was significantly different (p=0.0063); 1-,3-
      and 5-year OS were 100% and 85.9%, 88.3% and 61.9% and 65.1% and 58.0%,
      respectively. In multivariate analysis, no antiviral therapy with NA was an
      independent poor prognostic factor (hazard ratio (HR)=2.72; p=0.0229). However,
      after propensity case-matched analysis, disease-free and overall survival were
      not significantly different between the two groups. CONCLUSION: In a Japanese
      cohort, antiviral therapy with NAs might provide longer survival for
      postoperative HBV-related HCC patients compared to patients without antiviral
      therapy. However, deterministic evaluation was impossible by this study alone.

PMID- 25750324
TI  - EBV, HSV, CMV and HPV in laryngeal and oropharyngeal carcinoma in Polish
      patients.
AB  - The role of viruses in the etiology of oral cancer has been proposed in many
      studies. The aim of the present study was to analyze the prevalence of Epstein
      Barr virus, Human Herpes virus type 1, Cytomegalovirus and Human Papilloma virus
      among patients with oral squamous cell carcinoma in a Polish population. We
      investigated fresh-frozen tumor tissue fragments obtained from 80 patients with
      OSCC using the polymerase chain reaction assay. HPV was detected in 32.5% (22.5%
      were HPV 16), more often in laryngeal (36%) than in oropharyngeal carcinoma
      (26.6%). EBV was identified in 57.5%, HHV-1 in 7.5%, and CMV in 10% of patients.
      Co-infection with one or more viruses was detected in 30% of cases and most
      frequently it was co-infection with EBV and HPV (15%). Further studies are
      necessary to determine the potential role of EBV and the possible importance of
      HHV-1 as an infection co-factor in oropharyngeal cancer. 

PMID- 25750325
TI  - The alternatively spliced actinin-4 variant as a prognostic marker for metastasis
      in small-cell lung cancer.
AB  - BACKGROUND: The alternatively spliced actinin-4 variant (ACTN4va) is expressed in
      small-cell lung cancer (SCLC) and is thought to be a potential diagnostic marker.
      However, ACTN4va expression has not been examined in transbronchial biopsy
      specimens. MATERIALS AND METHODS: We retrospectively examined the relationship
      between ACTN4va expression, clinical factors and survival in 104 consecutive
      newly-diagnosed SCLC patients. RESULTS: Of the 104 screened cases, 83 (median
      age=69 years; transbronchial biopsy, 71) were included in our study. Survival was
      significantly different in the group with no distant metastasis (1996 vs. 422
      days, respectively; p=0.000115) but was not significantly different with regard
      to ACTN4va expression in the group with distant metastasis (293 vs. 254 days,
      respectively; p=0.678). CONCLUSION: ACTN4va expression was identifiable in small
      biopsy samples. ACTN4va expression was also significantly related to distant
      metastasis and could stratify SCLC patients according to prognosis.

PMID- 25750326
TI  - Validity of sentinel lymph node biopsy by ICG fluorescence for early head and
      neck cancer.
AB  - AIM: This study was designed to assess the validity of sentinel lymph node (SLN)
      biopsy using either the combination of indocyanine green (ICG) fluorescence and
      radioisotope (RI) or ICG-alone in SLN mapping for early head and neck cancer
      patients. PATIENTS AND METHODS: Nineteen patients received SLN biopsy with the
      following method. Thirteen patients received SLN biopsy with only RI, 2 patients
      with only ICG and 4 patients with the combination of ICG and RI. Detection time
      for each method of SLN biopsy was measured to evaluate the validity of SLN with
      the combination of ICG and RI. RESULTS: A total of 41 SLNs were identified by RI
      or ICG. All SLNs identified by ICG could be localized intraoperatively. The
      number of SLNs identified by the combination of ICG and RI was greater than that
      of SLNs identified by RI-alone. One of the patients who underwent SLN biopsy by
      RI-alone was diagnosed with a metastatic lymph node one year later, then
      underwent neck dissection. Mean detection time for SLN biopsy with ICG or with
      the combination of ICG and RI tended to be shorter than that of RI-alone.
      CONCLUSION: SLN biopsy with the combination of ICG and RI enabled us to identify
      SLNs more easily and rapidly than by using RI alone.

PMID- 25750327
TI  - Operation for preservation of lung parenchyma in central lung cancer--in vivo and
      ex situ reimplantation techniques.
AB  - BACKGROUND/AIM: Lobar reimplantation techniques enable the safe resection of lung
      cancer when pneumonectomy is not desirable or not feasible. We report our
      experience with this procedure. PATIENTS AND METHODS: Patients with difficult to
      resect upper/middle lobe non-small cell lung cancer were included. In situ
      reimplantation technique requires the reanastomosis of the pulmonary vein of the
      healthy lower lobe to the upper lobe stump; bench surgery reimplantation involves
      the ex vivo surgical treatment of the whole excised lung and subsequent
      reimplantation of the healthy remnant. RESULTS: Nine patients with upper-middle
      lobe lung cancer underwent in situ reimplantation, mean age=70.7+/-4.2 years; 6
      patients underwent ex situ resection, mean age=64.3+/-18.4 years. One obese
      patient succumbed due to thrombosis of the anastomosed pulmonary vein. One
      patient developed a stroke. CONCLUSION: The procedure was in general well
      tolerated and enables for curative resection of otherwise unresectable lung
      cancer.

PMID- 25750328
TI  - Circulating hepatocyte growth factor is correlated with resistance to cetuximab
      in metastatic colorectal cancer.
AB  - BACKGROUND/AIM: The epidermal growth factor family (EGF) has been suggested to
      influence the sensitivity to anti-epidermal growth factor receptor therapy. We
      examined the correlation between circulating levels of the epidermal growth
      factors amphiregulin and transforming growth factor-alpha (TGF-alpha) and the MET
      ligand hepatocyte growth factor and sensitivity to the anti-epidermal growth
      factor receptor antibody in colorectal cancer (CRC) patients. MATERIALS AND
      METHODS: Plasma levels of each ligand were measured by enzyme-linked
      immunosorbent assay in 51 patients with wild-type KRAS CRC. RESULTS: Patients
      with high hepatocyte growth factor (HGF) levels had a significantly lower disease
      control rate (DCR) and shorter median progression-free survival (PFS) and overall
      survival (OS) than those with low expression levels. Amphiregulin was correlated
      with objective response rate (ORR) but not with PFS or OS. Cetuximab response and
      survival were not associated with TGF-alpha. CONCLUSION: Circulating HGF may help
      identify CRC patients most likely to benefit from anti-epidermal growth factor
      receptor antibody therapy.

PMID- 25750329
TI  - Surgical loupes at 5.0* magnification and the VIO soft-coagulation system can
      prevent postoperative pancreatic fistula in duct-to-mucosa
      pancreaticojejunostomy.
AB  - BACKGROUND/AIM: Postoperative pancreatic fistula (POPF) remains a major
      complication after pancreaticoduodenectomy (PD). In this study, we examined
      whether our new method using surgical loupes at 5.0* magnification and the VIO
      soft coagulation system (SC) for duct-to-mucosa pancreaticojejunostomy (PJ) can
      prevent POPF. PATIENTS AND METHODS: A retrospective cohort study was performed in
      81 consecutive patients who underwent PD and duct-to-mucosa PJ for periampullary
      tumors by a single surgeon during a recent 5-year period from 2008 to 2012. These
      patients were divided into two groups according to the nature of the PJ; the
      conventional group (n=46) and the 5.0* loupes+SC group (n=35). Short-term
      surgical results including POPF were compared and an independent risk factor for
      POPF was identified using the stepwise logistic regression analysis in our
      series. RESULTS: The rate of Grade B/C POPF was significantly decreased in the
      5.0* loupes+SC group (2.9%) compared to that of the conventional group (9.9%,
      p=0.04). The absence of 5.0* loupes+SC for PJ was identified as the independent
      risk factor for Grade B/C POPF (odds ratio, 5.23; p-value, 0.03). CONCLUSION:
      5.0* surgical loupes+SC for duct-to-mucosa PJ could be used as a novel technique
      for preventing POPF after PD.

PMID- 25750330
TI  - Vinorelbine and cisplatin in patients with advanced non-small cell lung cancer
      with interstitial pneumonia.
AB  - AIM: The aim of the present study was to investigate the efficacy and
      tolerability of vinorelbine and cisplatin for the treatment of patients with
      advanced (stage IIIB, IV or relapse) non-small cell lung cancer (NSCLC) with
      interstitial pneumonia (IP). PATIENTS AND METHODS: A total of 67 patients treated
      with vinorelbine and cisplatin as a first-line chemo therapy between January 2002
      and December 2013 were retrospectively reviewed. RESULTS: The overall response
      rate was 34.3% [95% confidence interval (CI)=22.9%-45.7%). The median progression
      free survival, median overall survival, and 1-year survival rates were 3.7 months
      (95% CI=3.1-4.3 months), 7.4 months (95% CI=5.4-9.4 months), and 22.4% (95%
      CI=12.4%-32.4%), respectively. The incidence of acute exacerbation of IP
      following first-line chemotherapy was 10.4%. CONCLUSION: The combination of
      vinorelbine and cisplatin is a feasible treatment option for advanced NSCLC
      patients with IP, after careful consideration of the potential risks and benefits
      on an individual basis.

PMID- 25750331
TI  - Circulating pigment epithelium-derived factor (PEDF) is associated with
      pathological grade of prostate cancer.
AB  - BACKGROUND/AIM: Pigment epithelium-derived factor (PEDF) plays a protective role
      against oxidative stress. Levels of circulating PEDF have not been examined in
      patients with prostate cancer. We examined whether PEDF can be used to predict
      the clinical features of prostate cancer prior to therapy. MATERIALS AND METHODS:
      Two hundred patients with an abnormal serum level of prostate-specific antigen
      (PSA) who underwent biopsy between 2008 and 2011 were identified for
      retrospective analysis. We determined the relationship of the PEDF level to
      clinical parameters of prostate cancer. We measured levels of PEDF and 8-hydroxy
      2'-deoxyguanosine (8-OHdG) in all 200 patients, 100 of whom had histologically
      confirmed prostate cancer at the outset. We also investigated the PEDF expression
      in prostate cancer tissues by immunohistochemistry. RESULTS: The PEDF level was
      significantly higher in patients with prostate cancer than in those without.
      Statistical analysis confirmed that PEDF was significant, positively associated
      with pathological grading (Gleason score). However, PEDF expression was only
      detected in few prostate cancer cells by immunohistochemistry. Levels of the
      oxidative marker, 8-OHdG, in patients with prostate cancer are higher than in
      those without cancer. CONCLUSION: Preoperative PEDF measurement in patients with
      prostate cancer may provide clinically relevant information regarding the
      pathological grade of tumor.

PMID- 25750332
TI  - Primary malignant melanoma of the breast: case report and review of the
      literature.
AB  - BACKGROUND: Melanoma of the breast is a rare disease and may present as a
      metastatic manifestation of primary cutaneous melanoma or as primary malignant
      melanoma of the breast (PMMB). Clinical presentations of PMMB vary and surgery is
      the mainstay of treatment. CASE REPORT: We present the case of a 54-year-old
      woman with a primary malignant melanoma of the left breast. She was treated with
      mastectomy, axillary sentinel lymph node excision and primary reconstruction with
      a tissue expander. Final histology revealed a malignant melanoma with 10 cm in
      the largest diameter. Molecular characterization by DNA-sequencing showed B-RAF,
      N-RAS and c-kit wild types. Immunohistochemical characterization demonstrated
      weak expression of S100 and melan-A and strong expression of polyclonal S100.
      HMB45, tyrosine kinase and the cytokeratins AE1/AE3 and MNF 116 were not
      expressed. Lymphoma-specific markers (CD30, CD3, CD20) and sarcoma-specific
      markers (desmin, actin, CD34) were also negative. The tumor proliferation rate
      according to Mib1-staining was 90%. Staging of the abdomen, chest, head and bones
      showed no evidence of metastases. A dermatological examination showed no primary
      melanoma of the skin. Interferon-alpha was suggested as adjuvant therapy but
      declined by the patient. With a follow-up of 6 months, the patient is still alive
      with no evidence of disease. CONCLUSION: PMMB is rare and may be successfully
      treated with surgical excision. Locally advanced PMMB may occur without regional
      and distant metastases.

PMID- 25750333
TI  - Cyclin A correlates with YB1, progression and resistance to chemotherapy in human
      epithelial ovarian cancer.
AB  - BACKGROUND: Cyclin A is a cell-cycle regulatory gene and its overexpression
      promotes tumor cell growth. Y-Box-binding protein 1 (YB1) is a
      transcription/translation factor involved in tumor growth, invasion, and drug
      resistance. We investigated whether an association exists between protein
      products of these genes in epithelial ovarian cancer (EOC) specimens and
      clinicopathological parameters, patient response and EOC sensitivity to platinum
      based first-line chemotherapy. PATIENTS AND METHODS: Cyclin A and YB1 expression
      were analyzed by immunohistochemistry in 54 human primary EOC tissues.
      Immunolabeling of both proteins was graded according to their staining intensity
      (scale 0-3) and the proportion of immunostained cancer cells (scale 0-4) to
      obtain a staining index (SI; value=0-12). RESULTS: Significantly higher cyclin A
      immunostaining (SI>=4) in EOC specimens was discovered in patients with advanced
      (International Federation of Gynaecology and Obstetrics (FIGO) III and IV,
      p=0.003), poorly differentiated (G3, p<0.001) tumors, and tumors of those with
      residual disease>1 cm (p=0.001). YB1 immunostaining was significantly higher in
      EOCs from patients with suboptimal debulking (p=0.025). Over-expression of cyclin
      A (SI>=9) in EOCs was significantly linked with poorer patient response (p=0.001)
      and higher resistance of tumors to platinum-based first-line chemotherapy
      (p=0.007), while immunolabeling of YB1 in EOCs was not significantly associated
      with either of these variables (p>0.05). Cyclin A expression was significantly
      and positively correlated with that of YB1 (R=0.588, p<0.001). CONCLUSION:
      Increased cyclin A expression in EOC is related to a more aggressive tumor
      behavior and predicts the response of patients to first-line platinum-based
      chemotherapy.

PMID- 25750334
TI  - Clinical outcomes of patients with localized and locally advanced prostate cancer
      undergoing high-dose-rate brachytherapy with external-beam radiotherapy at our
      institute.
AB  - AIM: To report the clinical outcomes of localized and locally advanced prostate
      cancer patients undergoing high-dose-rate brachytherapy (HDR-BT) with external
      beam radiotherapy (HDR-BT+EBRT) at the Kanazawa University Hospital. PATIENTS AND
      METHODS: From 1999 until 2012, we examined 327 patients with T1c-T3bN0M0 prostate
      cancer that underwent HDR-BT+EBRT and were followed-up for >=1 year. Before 2005,
      treatment consisted of HDR-BT at 18 Gy/3 fractions and EBRT to the prostate at 44
      Gy/22 fractions, whereas after 2006, treatment consisted of HDR-BT at 19 Gy/2
      fractions and EBRT to the prostate at 46 Gy/23 fractions. RESULTS: Median age was
      68 years (range=45-84 years), median follow-up duration was 57 months (range=12
      148 months), and median prostate-specific antigen (PSA) level at diagnosis was
      9.2 ng/ml (range=2.6-458.6 ng/ml). The patients' clinical stages were T1c:82,
      T2a:112, T2b:70, T2c:5, T3a:29, T3b:29, and their Gleason score was <=6:120,
      7:108, >=8:99, respectively. The 5-year overall survival, and biochemical
      recurrence-free survival (bRFS) was 97.5% and 95.3%, respectively. Recurrence was
      reported in 20 cases (6.1%), and 11 patients died during follow-up, but only 1
      patient died of prostate cancer. The 5-year recurrence-free survival bRFS for the
      patients in low-risk, intermediate-risk, and high-risk groups according to the
      D'Amico risk classification criteria were 100%, 95.6%, and 90.7%, respectively.
      Regarding adverse events genitourinary toxicity was major, and thus, 8.8%
      patients had urethral stricture and 4.3% patients were classified as grade 3.
      CONCLUSION: HDR-BT+EBRT is considered a suitable treatment modality for localized
      and locally advanced prostate cancer, including high-risk cases. However,
      genitourinary toxicity is observed frequently, and therefore, it may be necessary
      to modify the therapeutic planning of the HDR-BT+EBRT modality.

PMID- 25750335
TI  - Impact of radical surgery on outcome in locally advanced breast cancer patients
      without metastasis at the time of diagnosis.
AB  - BACKGROUND/AIM: In the era of (18)F-fluorodeoxyglucose positron emission
      tomography/computed tomography ((18)FDG-PET/CT), more patients are being
      diagnosed with N3M0 disease. The objective of this study was to assess the
      prognostic impact of radical lymph node surgery (RLNS) in patients with locally
      advanced breast cancer classified as lymph node N3 disease according to the
      American Joint Committee on Cancer (AJCC) 2002 in whom there is no known distant
      metastasis and in the context of multimodal therapy. PATIENTS AND METHODS: This
      was a two-Center retrospective study that included patients with breast cancer
      classified as N3M0 after (18)FDG-PET/CT assessment. We reviewed the clinical
      characteristics, surgical treatment and oncological outcomes of those patients.
      RESULTS: Thirty-nine patients fulfilled the inclusion criteria. Multimodal
      treatment included neo-adjuvant chemotherapy (n=34), adjuvant radiotherapy
      (n=33), adjuvant chemotherapy (n=18) or neo- or adjuvant hormone therapy (n=17).
      Surgical treatment was not homogeneous. Eight patients had undergone RLNS and 31
      conventional axillary lymph node dissection (CD). There was no significant
      difference in median overall survival between the RLNS group and the CD group (32
      months (28-36) vs. 49 months (42-56) respectively (p=0.25)). The overall
      recurrence rate was 23%. Out of the 8 patients who had under gone RLNS, three had
      relapsed (two with distant metastases and one local). CONCLUSION: RLNS was not
      proven to be beneficial in our study. In order to guide surgical management for
      these patients, PET/CT and magnetic resonance imaging (MRI) could be of interest,
      therefore a pilot study to improve reproducible surgical management would be of
      interest.

PMID- 25750336
TI  - Prognostic factor of severe complications in patients with hypopharyngeal cancer
      with primary concurrent chemoradiotherapy.
AB  - BACKGROUND/AIM: Organ-preservation treatment for hypopharyngeal cancer has
      recently become a popular treatment option. However, the severe complications and
      poor quality of life after non-surgical treatment should be avoided. We accessed
      the laryngeal or pharyngeal dysfunction-related complications after concurrent
      chemoradiotherapy (CCRT) as the primary treatment for hypopharyngeal cancer.
      PATIENTS AND METHODS: Data concerning all patients treated for hypopharyngeal
      cancer with primary non-surgical treatment at the China Medical University
      Hospital from 2002 to 2012 were retrospectively reviewed. RESULTS: A total of 161
      patients were included with a median age of 56.6 years. The disease control rates
      (disease-free >12 months) and severe complication rates were correlated to the
      tumor (T) stage and nodal (N) stage. In the successful treatment group, the
      complication rate was related to the N stage. The overall pharyngeal dysfunction,
      laryngeal dysfunction and aspiration rates were 36%, 27% and 25%, respectively.
      For patients with T4a disease, hyoid bone invasion significantly increased the
      severe complication rate (p=0.0212). CONCLUSION: The treatment outcome was
      correlated to the T and N stage. A higher rate of laryngopharyngeal dysfunction
      occurred when treating hyoid bone invasion in T4a patients with primary non
      surgical treatment. In advanced stage, but still resectable hypopharyngeal
      tumors, the poorer quality of life due to non-function larynx was noted after
      treating with CCRT.

PMID- 25750337
TI  - The effect of re-operation on survival in patients with recurrent glioblastoma.
AB  - BACKGROUND: Treatment options for glioblastoma (GBM) at recurrence have limited
      efficacy. Re-surgery has been used for confirmation of recurrent disease and to
      provide relief of symptoms but the real impact on survival is unknown. PATIENTS
      AND METHODS: A retrospective analysis was performed for GBM patients followed
      between 01/2005 and 06/2010 at our Institution. RESULTS: Two hundred and thirty
      two patients with recurrent GBM were evaluated. One hundred and two patients
      (44%) were treated with re-surgery followed by chemotherapy and 130 patients
      (56%) with chemotherapy alone. In multivariate analysis, no significant effect of
      re-surgery was found, with age (p=0.001), MGMT methylation (p=0.002) and PFS at 6
      months (p=0.0001) being significant prognostic factors. CONCLUSION: Second
      surgery might have a limited impact in the clinical course of recurrent GBM
      patients.

PMID- 25750338
TI  - Significance of histopathological evaluation of pancreatic fibrosis to predict
      postoperative course after pancreatic surgery.
AB  - BACKGROUND/AIM: Pancreatic stellate cells (PSC) play a critical role in
      pancreatic fibrosis and the apparent diffusion coefficient (ADC) value based on
      the diffusion-weighted image (DWI) from magnetic resonance imaging (MRI) may be a
      predictor of tissue fibrosis. This study aimed to evaluate the pancreas texture
      from both histopathological and radiological viewpoints and to investigate the
      effect of pancreas texture on occurrence of postoperative pancreatic fistula
      (PF). PATIENTS AND METHODS: We divided 40 patients into soft-pancreas group and
      hard-pancreas group, according to the histopathological evaluation of pancreatic
      fibrosis. We compared ADC values and occurrences of PF between the two groups.
      RESULTS: Histopathological measurement lengths of interlobular and intralobular
      fibrosis increased significantly with the progression of fibrosis grade and PSC
      stage, while PSC stage correlated significantly with fibrosis grade (r=0.868,
      p<0.001). PF was detected in 14 out of 40 patients, including grade A in 7
      patients and grade B/C in 7 patients, but there were no operative deaths.
      Pancreas texture (soft/hard), determined based on the combination of fibrosis
      grade and PSC stage, was 16/10 (no PF) and 14/0 (grade A/B/C PF) and the
      difference in the incidence was significant (p=0.022). Though ADC value was
      significantly lower in the hard-compared to the soft-pancreas group (1.48+/-0.42
      vs. 1.73+/-0.27*10(-3) mm(2)/sec; p=0.033), there was no significant difference
      in ADC value between no PF versus grade A/B/C PF group. CONCLUSION:
      Histopathological evaluation of pancreas texture correlated negatively with ADC
      values and is critical to predict the occurrence of PF.

PMID- 25750339
TI  - Proton beam therapy combined with concurrent chemotherapy for esophageal cancer.
AB  - BACKGROUND/AIM: The aim of the present study was to evaluate the outcomes of
      proton beam therapy (PBT) concurrently combined with chemotherapy consisting of
      cisplatin and 5-fluorouracil for esophageal cancer. PATIENTS AND METHODS: Forty
      consecutive patients (stage I in 16 patients, II in 9 and III in 15) treated
      between 2008 and 2012 were evaluated. A total dose of 60 Gray equivalents (GyE)
      in 30 fractions was delivered, and an additional boost of 4-10 GyE was given when
      residual tumors were suspected. The median follow-up time was 24 months (range=7
      66 months). RESULTS: No cardio-pulmonary toxicities of grade 3 or higher were
      observed. Recurrences were observed in 16 patients, and the 2-year rates of
      disease-specific survival and locoregional control were 77% and 66%,
      respectively. CONCLUSION: Irrespective of the small sample size and short follow
      up time of the study, proton beam therapy combined with chemo therapy seems to be
      feasible for esophageal cancer.

PMID- 25750340
TI  - Role of p53 Codon72 SNP in breast cancer risk and anthracycline resistance.
AB  - BACKGROUND/AIM: We undertook a case-control and a case-case study to examine the
      possible association of p53 codon72 polymorphism with the breast cancer risk and
      resistance to anthracycline-based chemotherapy. PATIENTS AND METHODS: Case
      control study: This study enrolled 175 patients with breast cancer treated at the
      Salah Aziez Institute and 159 healthy Tunisian women (matched for age, ethnicity
      and origin), used as a control, with no clinical evidence of any neoplastic
      disorder. Case-Case study: 400 breast cancer patients, with invasive ductal
      carcinoma (IDC) treated with anthracycline based-chemotherapy. Genomic DNA was
      isolated from whole-blood leucocytes using the phenol-chloroform method.
      Anthracycline response was scored according to the World Health Organization
      (WHO) criteria. P53 codon72 polymorphism was genotyped using real-time polymerase
      chain reaction (RT-PCR) with the TaqMan method. Data were statistically analyzed
      using the Chi-square test. RESULTS: Clinical data revealed that among the 400
      patients, one quarter was resistant to chemotherapy treatment. Genetic data
      revealed that the p53 Arg72Pro genotype was found to be greatly associated with
      breast cancer risk (p<0.001), as well as tumor site (p=0.046). However,
      resistance to anthracycline-based chemotherapy does not seem to be correlated
      with p53 codon72 polymorphism in our population. Also, the distribution of tumor
      size, lymph node involvement and tumor grade was not significantly different
      among the polymorphic variants. CONCLUSION: We conclude that p53 codon72
      polymorphism is involved in susceptibility to developing breast cancer. It may be
      a factor of progression when breast sites are taken into account. However, there
      is no evidence indicating that Arg72Pro SNP may influence response to
      anthracycline-based chemotherapy.

PMID- 25750341
TI  - The impact of radiotherapy on symptoms, anxiety and QoL in patients with cancer.
AB  - AIM: To evaluate prospectively disease- and treatment-related symptoms, anxiety
      and quality of life (QoL), in patients with different types of cancer undergoing
      external-beam radiotherapy (RT) and examine the relationship among them, at
      baseline and at the end of the treatment. PATIENTS AND METHODS: This study
      included 90 patients with cancer. Patients' QoL was evaluated using the Linear
      Analog Scale Assessment (LASAs) questionnaire, anxiety was measured with the
      Spielberger state and trait inventory (STAI), while symptoms were assessed using
      the MD Anderson Symptom Inventory (MDASI). The assessments were carried-out at
      baseline and at the end of RT. RESULTS: At baseline, the QoL scores were reduced
      (7.5+/-6.5) and MDASI elevated (2.35+/-1.7). Patients' QoL was correlated with
      symptoms (r=-0.684, p=0.0005). A correlation was found between STAI-trait with
      MDASI scores (r=0.214, p=0.046). At the second assessment, there were significant
      correlations between MDASI and QoL (r=-0.68, p=0.0005). The STAI-trait had a
      moderate correlation with MDASI score (r=0.43, p=0.0005) and with QoL (r=-0.253,
      p=0.0017). CONCLUSION: The present study showed a significant impact of symptoms
      and high levels of anxiety following RT, which correlated with a compromised QoL.
      The worsening in patients' perception of their QoL did not seem to lead to a
      significant reduction in daily activities or treatment tolerance.

PMID- 25750342
TI  - Treatment of multiple unresectable basal cell carcinomas from Gorlin-Goltz
      syndrome: a case report.
AB  - BACKGROUND: Nevoid basal cell carcinoma syndrome (NBCCS), which is also known by
      other names, including Gorlin-Goltz syndrome and multiple basal-cell carcinoma
      (BCC) syndrome, is a rare multi-systemic disease inherited in a dominant
      autosomal manner with complete penetrance and variable expressivity. The main
      clinical manifestations include multiple BCCs, odontogenic keratocysts of the
      jaw, hyperkeratosis of the palms and soles, skeletal abnormalities, intracranial
      calcifications and facial deformities. PATIENTS AND METHODS: A 31-year-old male
      diagnosed with Gorlin-Goltz syndrome with multiple unresectable facial BCCs was
      treated with the Hedgehog inhibitor vismodegib. RESULTS: After one month of
      therapy on vismodegib, there were significant reductions in the size of multiple
      BCCs on the patient's face. The patient remains on this therapy. CONCLUSION:
      Hedgehog pathway inhibition is an effective strategy to treat unresectable BCCs
      from Gorlin-Goltz syndrome. Although vismodegib shows some promising clinical
      results in the early phase of its use, there are concerns of possible resistance
      developing within months. Duration of therapy, role of maintenance treatment and
      drug modification to reduce resistance need to be explored in future case
      studies.

PMID- 25750343
TI  - Role of salvage stereotactic body radiation therapy in post-surgical loco
      regional recurrence in a selected population of non-small cell lung cancer
      patients.
AB  - AIM: This is a retrospective analysis of a selected series of high-risk non-small
      cell lung cancer (NSCLC) patients with post-surgical loco-regional relapse
      treated with salvage stereotactic body radiotherapy (SBRT). Outcome and toxicity
      profiles were assessed. PATIENTS AND METHODS: Twenty-eight patients (unfit for
      surgery or systemic therapy) with 30 lesions underwent salvage SBRT as an
      alternative therapy because of advanced age, co-morbid conditions or no response
      obtained from other treatments. RESULTS: Complete and partial responses were 16%
      and 70%, respectively. Local progression was observed in 3 patients. Regional
      relapse occurred in 5 patients. Distant progression occurred in 10 patients. The
      2-year overall survival (OS) and disease-free survival (DFS) were 57.5% and
      36.6%, respectively. Radiation acute pneumonitis occurred as follows: three
      patients developed grade 1, two patients experienced grade 2 and one patient
      experienced grade 3 toxicity. CONCLUSION: Stereotactic body radiotherapy could
      have an alternative role in isolated loco-regional relapse in patients unfit or
      resistant to other therapies.

PMID- 25750344
TI  - Associations between driver gene mutations and cytotoxic chemosensitivity in
      patients with non-small cell lung cancer.
AB  - BACKGROUND/AIM: Patients with non-small cell lung cancer (NSCLC) harboring
      epidermal growth factor receptor (EGFR) gene mutations or echinoderm microtubule
      associated protein-like 4-anaplastic lymphoma kinase (EML4-ALK) rearrangement
      often have a better prognosis when they are treated with specific inhibitors than
      when treated with cytotoxic agents. However, the associations between gene
      mutations and cytotoxic chemosensitivity are still unclear. The objective of the
      present study was to identify which clinicopathological factors, including
      genetic mutations, influence chemosensitivity, determined using the succinate
      dehydrogenase inhibition (SDI) test in patients with NSCLC. MATERIALS AND
      METHODS: The chemosensitivity of tumor tissues from 96 patients with NSCLC who
      underwent surgical resection was evaluated using the SDI test. RESULTS: In
      patients with adenocarcinoma, tumors with EGFR gene mutations were significantly
      more sensitive to 5-fluorouracil (5-FU) than tumors without EGFR gene mutations
      (p<0.0149). CONCLUSION: Our data suggest that patients with adenocarcinoma
      harboring EGFR gene mutations may be susceptible to 5-FU.

PMID- 25750345
TI  - Lack of difference in acute nephrotoxicity of intravenous bisphosphonates
      zoledronic acid and ibandronate in women with breast cancer and bone metastases.
AB  - BACKGROUND: More than 50% of patients with advanced breast cancer develop bone
      metastases that may lead to multiple complications such as pathological
      fractures, bone pain or hypercalcaemia. The standard treatment, besides
      endocrine, targeted-therapy or chemotherapy, is the use of bisphosphonates.
      However, one of their main adverse side-effects is bisphosphonate-induced
      nephrotoxicity. The mechanism by which the latter occurs is not well-understood,
      although emerging evidence suggests that the effect of bisphosphonates on the
      kidney may differ between agents. PATIENTS AND METHODS: The aim of this
      evaluation was to compare the renal toxicity of 6 mg ibandronate i.v. versus 4 mg
      zoledronic acid i.v. over a period of six months in women with breast cancer and
      bone metastases. A prospective randomized trial was carried out to examine
      specific kidney and other parameters (alpha1- and beta2-microglobulin, albumin,
      alpha2-macroglobulin, IgG and C-reactive protein (CRP) generated from spontaneous
      urine samples from 17 patients of each group. RESULTS: We were unable to find any
      significant difference between the two treatment groups with regard to renal
      toxicity. All patients, independently of the applied bisphosphonate, experienced
      only temporary renal dysfunction without any evidence of irreversible damage in
      terms of acute nephrotoxicity during the study period. alpha1-Microglobulin, a
      marker for proximal tubular damage, in particular, was not differently elevated
      in either group. CONCLUSION: Both applied bisphosphonates were found to be well
      tolerated and safe with regard to renal toxicity during a six-month treatment
      period in patients with otherwise healthy kidneys having advanced breast cancer
      and bone metastases.

PMID- 25750346
TI  - Biomarkers of apoptosis and necrosis in patients with hepatocellular carcinoma
      treated with sorafenib.
AB  - BACKGROUND/AIM: Sorafenib is the medical reference for treatment of
      hepatocellular carcinoma (HCC). Multiple forms of cytotoxicity are induced by
      sorafenib in HCC cells in vitro but it is unclear what extent of apoptosis and
      necrosis is induced in HCC patients receiving sorafenib. PATIENTS AND METHODS:
      The M30 and M65 biomarkers, which reflect the release of cytokeratin-18 and its
      apoptotic cleavage fragments, were measured in patients with HCC (n=36) and
      matched patients with cirrhosis (n=47). A serum sample was collected from 20
      patients with HCC four weeks after the onset of treatment with sorafenib.
      RESULTS: Basal serum levels of M30 and M65 were increased in patients with HCC
      compared to those with uncomplicated cirrhosis. No statistically significant
      increase in the level of M30 or M65 was found in the sera of patients with HCC
      after sorafenib. CONCLUSION: The findings indicate that sorafenib is not a potent
      inducer of HCC cell death in most patients.

PMID- 25750347
TI  - Risk of second primary cancer in patients with B-cell non-Hodgkin lymphoma
      receiving rituximab-containing chemotherapy: a nationwide population-based study.
AB  - AIM: This study aimed to evaluate the risk of second primary cancer (SPC) in
      patients receiving rituximab-containing chemotherapy. PATIENTS AND METHODS: A
      nationwide, population-based study was conducted using the National Health
      Insurance Database of Taiwan. Propensity score matching was performed to correct
      sample selection bias and logistic regression analysis was used to calculate odds
      ratios. RESULTS: Patients receiving rituximab-containing chemotherapy or
      conventional chemotherapy were enrolled. After adjustment by propensity score
      matching, there were 1,607 patients in each group. SPC was noted in 11 patients
      (0.68%) with rituximab-containing chemotherapy and in 19 patients (1.18%) with
      conventional chemotherapy (p=0.142). There was no significant difference in the
      age distribution at onset of SPC (p=0.327). Multivariate logistic regression
      analysis revealed rituximab-containing chemotherapy was not associated with risk
      of SPC (odds ratio (OR)=0.58; 95% confidence interval (CI)=0.28-1.23; p=0.157).
      CONCLUSION: Incorporation of rituximab into conventional anti-lymphoma
      chemotherapy did not increase the risk of SPC in patients with B-cell non-Hodgkin
      lymphoma (NHL).

PMID- 25750348
TI  - Safety and efficacy of adjuvant therapy with oxaliplatin, leucovorin and 5
      fluorouracil after mesorectal excision with lateral pelvic lymph node dissection
      for stage iii lower rectal cancer.
AB  - BACKGROUND/AIM: Preoperative chemoradiotherapy followed by total mesorectal
      excision (TME) is the standard treatment for stage III lower rectal cancer
      worldwide. However, in Japan, the standard treatment is TME with lateral pelvic
      lymph node dissection (LPLD) followed by adjuvant chemotherapy. We examined the
      safety and efficacy of adjuvant therapy with oxaliplatin, leucovorin, and 5
      fluorouracil (modified FOLFOX6) after TME with LPLD. PATIENTS AND METHODS: This
      retrospective study included 33 patients who received modified FOLFOX6 after TME
      with LPLD for stage III lower rectal cancer. RESULTS: The overall completion rate
      of 12 cycles of adjuvant modified FOLFOX6 was 76%. Grade 3 or 4 neutropenia was
      observed in eight patients (24%). Sensory neuropathy was observed in 32 patients
      (97%) with 4 (12%) having a grade 3 event. The disease-free survival (DFS) rate
      was 45% at 3 years. CONCLUSION: Adjuvant modified FOLFOX6 was feasible in
      patients with stage III lower rectal cancer after TME with LPLD.

PMID- 25750408
TI  - Changes in plant species composition of coastal dune habitats over a 20-year
      period.
AB  - Coastal sandy ecosystems are increasingly being threatened by human pressure,
      causing loss of biodiversity, habitat degradation and landscape modifications.
      However, there are still very few detailed studies focussing on compositional
      changes in coastal dune plant communities over time. In this work, we
      investigated how coastal dune European Union (EU) habitats (from pioneer annual
      beach communities to Mediterranean scrubs on the landward fixed dunes) have
      changed during the last 20 years. Using phytosociological releves conducted in
      1989-90 and in 2010-12, we investigated changes in floristic composition over
      time. We then compared plant cover and the proportion of ruderal, alien and
      habitat diagnostic species ('focal species') in the two periods. Finally, we used
      Ellenberg indicator values to define the 'preferences' of the plant species for
      temperature and moisture. We found that only fore dune habitats showed
      significant differences in species cover between the two time periods, with
      higher plant cover in the more recent releves and a significant increase in
      thermophilic species. Although previous studies have demonstrated consistent
      habitat loss in this area, we observed that all coastal dune plant communities
      remain well represented, after a 20-year period. However, fore dunes have been
      experiencing significant compositional changes. Although we cannot confirm
      whether the observed changes are strictly related to climatic changes, to human
      pressure or to both, we hypothesize that a moderate increment in average yearly
      temperature may have promoted the increase in plant cover and the spread of
      thermophilic species. Thus, even though human activities are major driving forces
      of change in coastal dune vegetation, at the community scale climatic factors may
      also play important roles. Our study draws on re-visitation studies which appear
      to constitute a powerful tool for the assessment of the conservation status of EU
      habitats. 

PMID- 25750409
TI  - Relative importance of phenotypic trait matching and species' abundances in
      determining plant-avian seed dispersal interactions in a small insular community.
AB  - Network theory has provided a general way to understand mutualistic plant-animal
      interactions at the community level. However, the mechanisms responsible for
      interaction patterns remain controversial. In this study we use a combination of
      statistical models and probability matrices to evaluate the relative importance
      of species morphological and nutritional (phenotypic) traits and species
      abundance in determining interactions between fleshy-fruited plants and birds
      that disperse their seeds. The models included variables associated with species
      abundance, a suite of variables associated with phenotypic traits (fruit
      diameter, bird bill width, fruit nutrient compounds), and the species identity of
      the avian disperser. Results show that both phenotypic traits and species
      abundance are important determinants of pairwise interactions. However, when
      considered separately, fruit diameter and bill width were more important in
      determining seed dispersal interactions. The effect of fruit compounds was less
      substantial and only important when considered together with abundance-related
      variables and/or the factor 'animal species'. 

PMID- 25750410
TI  - Evolutionary genetics of insect innate immunity.
AB  - Patterns of evolution in immune defense genes help to understand the evolutionary
      dynamics between hosts and pathogens. Multiple insect genomes have been
      sequenced, with many of them having annotated immune genes, which paves the way
      for a comparative genomic analysis of insect immunity. In this review, I
      summarize the current state of comparative and evolutionary genomics of insect
      innate immune defense. The focus is on the conserved and divergent components of
      immunity with an emphasis on gene family evolution and evolution at the sequence
      level; both population genetics and molecular evolution frameworks are
      considered. 

PMID- 25750411
TI  - Integrating evo-devo with ecology for a better understanding of phenotypic
      evolution.
AB  - Evolutionary developmental biology (evo-devo) has provided invaluable
      contributions to our understanding of the mechanistic relationship between
      genotypic and phenotypic change. Similarly, evolutionary ecology has greatly
      advanced our understanding of the relationship between the phenotype and the
      environment. To fully understand the evolution of organismal diversity, a
      thorough integration of these two fields is required. This integration remains
      highly challenging because model systems offering a rich ecological and
      evolutionary background, together with the availability of developmental genetic
      tools and genomic resources, are scarce. In this review, we introduce the semi
      aquatic bugs (Gerromorpha, Heteroptera) as original models well suited to study
      why and how organisms diversify. The Gerromorpha invaded water surfaces over 200
      mya and diversified into a range of remarkable new forms within this new
      ecological habitat. We summarize the biology and evolutionary history of this
      group of insects and highlight a set of characters associated with the habitat
      change and the diversification that followed. We further discuss the
      morphological, behavioral, molecular and genomic tools available that together
      make semi-aquatic bugs a prime model for integration across disciplines. We
      present case studies showing how the implementation and combination of these
      approaches can advance our understanding of how the interaction between
      genotypes, phenotypes and the environment drives the evolution of distinct
      morphologies. Finally, we explain how the same set of experimental designs can be
      applied in other systems to address similar biological questions. 

PMID- 25750412
TI  - Unsteady turbulent boundary layers in swimming rainbow trout.
AB  - The boundary layers of rainbow trout, Oncorhynchus mykiss, swimming at 1.02+/
      0.09 L s(-1) (mean+/-s.d., N=4), were measured by the particle image velocimetry
      (PIV) technique at a Reynolds number of 4*10(5). The boundary layer profile
      showed unsteadiness, oscillating above and beneath the classical logarithmic law
      of the wall with body motion. Across the entire surface regions that were
      measured, local Reynolds numbers based on momentum thickness, which is the
      distance that is perpendicular to the fish surface through which the boundary
      layer momentum flows at free-stream velocity, were greater than the critical
      value of 320 for the laminar-to-turbulent transition. The skin friction was
      dampened on the convex surface while the surface was moving towards a free-stream
      flow and increased on the concave surface while retreating. These observations
      contradict the result of a previous study using different species swimming by
      different methods. Boundary layer compression accompanied by an increase in local
      skin friction was not observed. Thus, the overall results may not support
      absolutely the Bone-Lighthill boundary layer thinning hypothesis that the
      undulatory motions of swimming fish cause a large increase in their friction drag
      because of the compression of the boundary layer. In some cases, marginal flow
      separation occurred on the convex surface in the relatively anterior surface
      region, but the separated flow reattached to the fish surface immediately
      downstream. Therefore, we believe that a severe impact due to induced drag
      components (i.e. pressure drag) on the swimming performance, an inevitable
      consequence of flow separation, was avoided.

PMID- 25750413
TI  - Paracellular pathway remodeling enhances sodium secretion by teleost fish in
      hypersaline environments.
AB  - In vertebrate salt-secreting epithelia, Na(+) moves passively down an
      electrochemical gradient via a paracellular pathway. We assessed how this pathway
      is modified to allow Na(+) secretion in hypersaline environments. Mummichogs
      (Fundulus heteroclitus) acclimated to hypersaline [2* seawater (2SW), 640/00] for
      30 days developed invasive projections of accessory cells with an increased area
      of tight junctions, detected by punctate distribution of CFTR (cystic fibrosis
      transmembrane conductance regulator) immunofluorescence and transmission electron
      miscroscopy of the opercular epithelia, which form a gill-like tissue rich in
      ionocytes. Distribution of CFTR was not explained by membrane raft organization,
      because chlorpromazine (50 MUmol l(-1)) and filipin (1.5 MUmol l(-1)) did not
      affect opercular epithelia electrophysiology. Isolated opercular epithelia bathed
      in SW on the mucosal side had a transepithelial potential (Vt) of +40.1+/-0.9 mV
      (N=24), sufficient for passive Na(+) secretion (Nernst equilibrium
      voltage=ENa=+24.11 mV). Opercular epithelia from fish acclimated to 2SW and
      bathed in 2SW had higher Vt of +45.1+/-1.2 mV (N=24), sufficient for passive
      Na(+) secretion (ENa=+40.74 mV), but with diminished net driving force.
      Bumetanide block of Cl(-) secretion reduced Vt by 45% and 29% in SW and 2SW,
      respectively, a decrease in the driving force for Na(+) extrusion. Estimates of
      shunt conductance from epithelial conductance (Gt) versus short-circuit current
      (Isc) plots (extrapolation to zero Isc) suggested a reduction in total epithelial
      shunt conductance in 2SW-acclimated fish. In contrast, the morphological
      elaboration of tight junctions, leading to an increase in accessory-cell-ionocyte
      contact points, suggests an increase in local paracellular conductance,
      compensating for the diminished net driving force for Na(+) and allowing salt
      secretion, even in extreme salinities.

PMID- 25750415
TI  - Vision in avian emberizid foragers: maximizing both binocular vision and fronto
      lateral visual acuity.
AB  - Avian species vary in their visual system configuration, but previous studies
      have often compared single visual traits between two to three distantly related
      species. However, birds use different visual dimensions that cannot be maximized
      simultaneously to meet different perceptual demands, potentially leading to trade
      offs between visual traits. We studied the degree of inter-specific variation in
      multiple visual traits related to foraging and anti-predator behaviors in nine
      species of closely related emberizid sparrows, controlling for phylogenetic
      effects. Emberizid sparrows maximize binocular vision, even seeing their bill
      tips in some eye positions, which may enhance the detection of prey and
      facilitate food handling. Sparrows have a single retinal center of acute vision
      (i.e. fovea) projecting fronto-laterally (but not into the binocular field). The
      foveal projection close to the edge of the binocular field may shorten the time
      to gather and process both monocular and binocular visual information from the
      foraging substrate. Contrary to previous work, we found that species with larger
      visual fields had higher visual acuity, which may compensate for larger blind
      spots (i.e. pectens) above the center of acute vision, enhancing predator
      detection. Finally, species with a steeper change in ganglion cell density across
      the retina had higher eye movement amplitude, probably due to a more pronounced
      reduction in visual resolution away from the fovea, which would need to be moved
      around more frequently. The visual configuration of emberizid passive prey
      foragers is substantially different from that of previously studied avian groups
      (e.g. sit-and-wait and tactile foragers).

PMID- 25750414
TI  - Expression and light-triggered movement of rhodopsins in the larval visual system
      of mosquitoes.
AB  - During the larval stages, the visual system of the mosquito Aedes aegypti
      contains five stemmata, often referred to as larval ocelli, positioned laterally
      on each side of the larval head. Here we show that stemmata contain two
      photoreceptor types, distinguished by the expression of different rhodopsins. The
      rhodopsin Aaop3 (GPROP3) is expressed in the majority of the larval
      photoreceptors. There are two small clusters of photoreceptors located within the
      satellite and central stemmata that express the rhodopsin Aaop7 (GPROP7) instead
      of Aaop3. Electroretinogram analysis of transgenic Aaop7 Drosophila indicates
      that Aaop3 and Aaop7, both classified as long-wavelength rhodopsins, possess
      similar but not identical spectral properties. Light triggers an extensive
      translocation of Aaop3 from the photosensitive rhabdoms to the cytoplasmic
      compartment, whereas light-driven translocation of Aaop7 is limited. The results
      suggest that these photoreceptor cell types play distinct roles in larval vision.
      An additional component of the larval visual system is the adult compound eye,
      which starts to develop at the anterior face of the larval stemmata during the
      1st instar stage. The photoreceptors of the developing compound eye show
      rhodopsin expression during the 4th larval instar stage, consistent with
      indications from previous reports that the adult compound eye contributes to
      larval and pupal visual capabilities.

PMID- 25750416
TI  - Effect of light intensity on flight control and temporal properties of
      photoreceptors in bumblebees.
AB  - To control flight, insects rely on the pattern of visual motion generated on the
      retina as they move through the environment. When light levels fall, vision
      becomes less reliable and flight control thus becomes more challenging. Here, we
      investigated the effect of light intensity on flight control by filming the
      trajectories of free-flying bumblebees (Bombus terrestris, Linnaeus 1758) in an
      experimental tunnel at different light levels. As light levels fell, flight speed
      decreased and the flight trajectories became more tortuous but the bees were
      still remarkably good at centring their flight about the tunnel's midline. To
      investigate whether this robust flight performance can be explained by visual
      adaptations in the bumblebee retina, we also examined the response speed of the
      green-sensitive photoreceptors at the same light intensities. We found that the
      response speed of the photoreceptors significantly decreased as light levels
      fell. This indicates that bumblebees have both behavioural (reduction in flight
      speed) and retinal (reduction in response speed of the photoreceptors)
      adaptations to allow them to fly in dim light. However, the more tortuous flight
      paths recorded in dim light suggest that these adaptations do not support flight
      with the same precision during the twilight hours of the day.

PMID- 25750417
TI  - Detecting and overcoming systematic bias in high-throughput screening
      technologies: a comprehensive review of practical issues and methodological
      solutions.
AB  - Significant efforts have been made recently to improve data throughput and data
      quality in screening technologies related to drug design. The modern
      pharmaceutical industry relies heavily on high-throughput screening (HTS) and
      high-content screening (HCS) technologies, which include small molecule,
      complementary DNA (cDNA) and RNA interference (RNAi) types of screening. Data
      generated by these screening technologies are subject to several environmental
      and procedural systematic biases, which introduce errors into the hit
      identification process. We first review systematic biases typical of HTS and HCS
      screens. We highlight that study design issues and the way in which data are
      generated are crucial for providing unbiased screening results. Considering
      various data sets, including the publicly available ChemBank data, we assess the
      rates of systematic bias in experimental HTS by using plate-specific and assay
      specific error detection tests. We describe main data normalization and
      correction techniques and introduce a general data preprocessing protocol. This
      protocol can be recommended for academic and industrial researchers involved in
      the analysis of current or next-generation HTS data. 

PMID- 25750418
TI  - EpIC: a rational pipeline for epitope immunogenicity characterization.
AB  - Efforts to develop peptide-based vaccines, in particular those requiring site
      specific targeting of self-proteins, rely on the ability to optimize the
      immunogenicity of the peptide epitopes. Currently, screening of candidate
      vaccines is typically performed through low-throughput, high-cost animal trials.
      To improve on this we present the program EpIC, which enables high-throughput
      prediction of peptide immunogenicity based on the endogenous occurrence of B-cell
      epitopes within native protein sequences. This information informs rational
      selection of immunogenicity-optimized epitopes for peptide vaccines. AVAILABILITY
      AND IMPLEMENTATION: EpIC is available as a web server at
      http://saphire.usask.ca/saphire/epic.

PMID- 25750419
TI  - Contribution of glutathione to the control of cellular redox homeostasis under
      toxic metal and metalloid stress.
AB  - The accumulation of toxic metals and metalloids, such as cadmium (Cd), mercury
      (Hg), or arsenic (As), as a consequence of various anthropogenic activities,
      poses a serious threat to the environment and human health. The ability of plants
      to take up mineral nutrients from the soil can be exploited to develop
      phytoremediation technologies able to alleviate the negative impact of toxic
      elements in terrestrial ecosystems. However, we must select plant species or
      populations capable of tolerating exposure to hazardous elements. The tolerance
      of plant cells to toxic elements is highly dependent on glutathione (GSH)
      metabolism. GSH is a biothiol tripeptide that plays a fundamental dual role:
      first, as an antioxidant to mitigate the redox imbalance caused by toxic
      metal(loid) accumulation, and second as a precursor of phytochelatins (PCs),
      ligand peptides that limit the free ion cellular concentration of those
      pollutants. The sulphur assimilation pathway, synthesis of GSH, and production of
      PCs are tightly regulated in order to alleviate the phytotoxicity of different
      hazardous elements, which might induce specific stress signatures. This review
      provides an update on mechanisms of tolerance that depend on biothiols in plant
      cells exposed to toxic elements, with a particular emphasis on the Hg-triggered
      responses, and considering the contribution of hormones to their regulation. 

PMID- 25750420
TI  - Cysteines under ROS attack in plants: a proteomics view.
AB  - Plants generate reactive oxygen species (ROS) as part of their metabolism and in
      response to various external stress factors, potentially causing significant
      damage to biomolecules and cell structures. During the course of evolution,
      plants have adapted to ROS toxicity, and use ROS as signalling messengers that
      activate defence responses. Cysteine (Cys) residues in proteins are one of the
      most sensitive targets for ROS-mediated post-translational modifications, and
      they have become key residues for ROS signalling studies. The reactivity of Cys
      residues towards ROS, and their ability to react to different oxidation states,
      allow them to appear at the crossroads of highly dynamic oxidative events. As
      such, a redox-active cysteine can be present as S-glutathionylated (-SSG),
      disulfide bonded (S-S), sulfenylated (-SOH), sulfinylated (-SO2H), and
      sulfonylated (-SO3H). The sulfenic acid (-SOH) form has been considered as part
      of ROS-sensing pathways, as it leads to further modifications which affect
      protein structure and function. Redox proteomic studies are required to
      understand how and why cysteines undergo oxidative post-translational
      modifications and to identify the ROS-sensor proteins. Here, we update current
      knowledge of cysteine reactivity with ROS. Further, we give an overview of
      proteomic techniques that have been applied to identify different redox-modified
      cysteines in plants. There is a particular focus on the identification of
      sulfenylated proteins, which have the potential to be involved in plant signal
      transduction.

PMID- 25750421
TI  - Transcription profiling of the chilling requirement for bud break in apples: a
      putative role for FLC-like genes.
AB  - Apple production depends on the fulfilment of a chilling requirement for bud
      dormancy release. Insufficient winter chilling results in irregular and
      suboptimal bud break in the spring, with negative impacts on apple yield. Trees
      from apple cultivars with contrasting chilling requirements for bud break were
      used to investigate the expression of the entire set of apple genes in response
      to chilling accumulation in the field and controlled conditions. Total RNA was
      analysed on the AryANE v.1.0 oligonucleotide microarray chip representing 57,000
      apple genes. The data were tested for functional enrichment, and differential
      expression was confirmed by real-time PCR. The largest number of differentially
      expressed genes was found in samples treated with cold temperatures. Cold
      exposure mostly repressed expression of transcripts related to photosynthesis,
      and long-term cold exposure repressed flavonoid biosynthesis genes. Among the
      differentially expressed selected candidates, we identified genes whose
      annotations were related to the circadian clock, hormonal signalling, regulation
      of growth, and flower development. Two genes, annotated as FLOWERING LOCUS C-like
      and MADS AFFECTING FLOWERING, showed strong differential expression in several
      comparisons. One of these two genes was upregulated in most comparisons involving
      dormancy release, and this gene's chromosomal position co-localized with the
      confidence interval of a major quantitative trait locus for the timing of bud
      break. These results indicate that photosynthesis and auxin transport are major
      regulatory nodes of apple dormancy and unveil strong candidates for the control
      of bud dormancy.

PMID- 25750422
TI  - Molecular control of wood formation in trees.
AB  - Wood (also termed secondary xylem) is the most abundant biomass produced by
      plants, and is one of the most important sinks for atmospheric carbon dioxide.
      The development of wood begins with the differentiation of the lateral meristem,
      vascular cambium, into secondary xylem mother cells followed by cell expansion,
      secondary wall deposition, programmed cell death, and finally heartwood
      formation. Significant progress has been made in the past decade in uncovering
      the molecular players involved in various developmental stages of wood formation
      in tree species. Hormonal signalling has been shown to play critical roles in
      vascular cambium cell proliferation and a peptide-receptor-transcription factor
      regulatory mechanism similar to that controlling the activity of apical meristems
      is proposed to be involved in the maintenance of vascular cambium activity. It
      has been demonstrated that the differentiation of vascular cambium into xylem
      mother cells is regulated by plant hormones and HD-ZIP III transcription factors,
      and the coordinated activation of secondary wall biosynthesis genes during wood
      formation is mediated by a transcription network encompassing secondary wall NAC
      and MYB master switches and their downstream transcription factors. Most genes
      encoding the biosynthesis enzymes for wood components (cellulose, xylan,
      glucomannan, and lignin) have been identified in poplar and a number of them have
      been functionally characterized. With the availability of genome sequences of
      tree species from both gymnosperms and angiosperms, and the identification of a
      suite of wood-associated genes, it is expected that our understanding of the
      molecular control of wood formation in trees will be greatly accelerated. 

PMID- 25750423
TI  - Oxidative post-translational modifications of cysteine residues in plant signal
      transduction.
AB  - In plants, fluctuation of the redox balance by altered levels of reactive oxygen
      species (ROS) can affect many aspects of cellular physiology. ROS homeostasis is
      governed by a diversified set of antioxidant systems. Perturbation of this
      homeostasis leads to transient or permanent changes in the redox status and is
      exploited by plants in different stress signalling mechanisms. Understanding how
      plants sense ROS and transduce these stimuli into downstream biological responses
      is still a major challenge. ROS can provoke reversible and irreversible
      modifications to proteins that act in diverse signalling pathways. These
      oxidative post-translational modifications (Ox-PTMs) lead to oxidative damage
      and/or trigger structural alterations in these target proteins. Characterization
      of the effect of individual Ox-PTMs on individual proteins is the key to a better
      understanding of how cells interpret the oxidative signals that arise from
      developmental cues and stress conditions. This review focuses on ROS-mediated Ox
      PTMs on cysteine (Cys) residues. The Cys side chain, with its high nucleophilic
      capacity, appears to be the principle target of ROS. Ox-PTMs on Cys residues
      participate in various signalling cascades initiated by plant stress hormones. We
      review the mechanistic aspects and functional consequences of Cys Ox-PTMs on
      specific target proteins in view of stress signalling events. 

PMID- 25750425
TI  - Heat tolerance around flowering in wheat identified as a key trait for increased
      yield potential in Europe under climate change.
AB  - To deliver food security for the 9 billon population in 2050, a 70% increase in
      world food supply will be required. Projected climatic and environmental changes
      emphasize the need for breeding strategies that delivers both a substantial
      increase in yield potential and resilience to extreme weather events such as heat
      waves, late frost, and drought. Heat stress around sensitive stages of wheat
      development has been identified as a possible threat to wheat production in
      Europe. However, no estimates have been made to assess yield losses due to
      increased frequency and magnitude of heat stress under climate change. Using
      existing experimental data, the Sirius wheat model was refined by incorporating
      the effects of extreme temperature during flowering and grain filling on
      accelerated leaf senescence, grain number, and grain weight. This allowed us, for
      the first time, to quantify yield losses resulting from heat stress under climate
      change. The model was used to optimize wheat ideotypes for CMIP5-based climate
      scenarios for 2050 at six sites in Europe with diverse climates. The yield
      potential for heat-tolerant ideotypes can be substantially increased in the
      future (e.g. by 80% at Seville, 100% at Debrecen) compared with the current
      cultivars by selecting an optimal combination of wheat traits, e.g. optimal
      phenology and extended duration of grain filling. However, at two sites, Seville
      and Debrecen, the grain yields of heat-sensitive ideotypes were substantially
      lower (by 54% and 16%) and more variable compared with heat-tolerant ideotypes,
      because the extended grain filling required for the increased yield potential was
      in conflict with episodes of high temperature during flowering and grain filling.
      Despite much earlier flowering at these sites, the risk of heat stress affecting
      yields of heat-sensitive ideotypes remained high. Therefore, heat tolerance in
      wheat is likely to become a key trait for increased yield potential and yield
      stability in southern Europe in the future. 

PMID- 25750424
TI  - Identification of rice cornichon as a possible cargo receptor for the Golgi
      localized sodium transporter OsHKT1;3.
AB  - Membrane proteins are synthesized and folded in the endoplasmic reticulum (ER),
      and continue their path to their site of residence along the secretory pathway.
      The COPII system has been identified as a key player for selecting and directing
      the fate of membrane and secretory cargo proteins. Selection of cargo proteins
      within the COPII vesicles is achieved by cargo receptors. The cornichon cargo
      receptor belongs to a conserved protein family found in eukaryotes that has been
      demonstrated to participate in the selection of integral membrane proteins as
      cargo for their correct targeting. Here it is demonstrated at the cellular level
      that rice cornichon OsCNIH1 interacts with OsHKT1;3 and, in yeast cells, enables
      the expression of the sodium transporter to the Golgi apparatus. Physical and
      functional HKT-cornichon interactions are confirmed by the mating-based split
      ubiquitin system, bimolecular fluorescence complementation, and Xenopus oocyte
      and yeast expression systems. The interaction between the two proteins occurs in
      the ER of plant cells and their co-expression in oocytes leads to the
      sequestration of the transporter in the ER. In the yeast cornichon mutant erv14,
      OsHKT1;3 is mistargeted, preventing the toxic effects of sodium transport in the
      cell observed in wild-type cells or in the erv14 mutant that co-expressed
      OsHKT1;3 with either OsCNIH1 or Erv14p. Identification and characterization of
      rice cornichon as a possible cargo receptor opens up the opportunity to improve
      our knowledge on membrane protein targeting in plant cells. 

PMID- 25750426
TI  - Nitric oxide is a ubiquitous signal for maintaining redox balance in plant cells:
      regulation of ascorbate peroxidase as a case study.
AB  - Oxidative and nitrosative stresses and their respective antioxidant responses are
      common metabolic adjustments operating in all biological systems. These stresses
      result from an increase in reactive oxygen species (ROS) and reactive nitrogen
      species (RNS) and an imbalance in the antioxidant response. Plants respond to ROS
      and RNS accumulation by increasing the level of the antioxidant molecules
      glutathione and ascorbate and by activating specific antioxidant enzymes. Nitric
      oxide (NO) is a free radical considered to be toxic or protective depending on
      its concentration, combination with ROS compounds, and subcellular localization.
      In this review we focus on the mechanisms of NO action in combination with ROS on
      the regulation of the antioxidant system in plants. In particular, we describe
      the redox post-translational modifications of cytosolic ascorbate peroxidase and
      its influence on enzyme activity. The regulation of ascorbate peroxidase activity
      by NO as a redox sensor of acute oxidative stress or as part of a hormone-induced
      signalling pathway leading to lateral root development is presented and
      discussed. 

PMID- 25750427
TI  - Root length densities of UK wheat and oilseed rape crops with implications for
      water capture and yield.
AB  - Root length density (RLD) was measured to 1 m depth for 17 commercial crops of
      winter wheat (Triticum aestivum) and 40 crops of winter oilseed rape [Brassica
      napus; oilseed rape (OSR)] grown in the UK between 2004 and 2013. Taking the
      critical RLD (cRLD) for water capture as 1cm cm(-3), RLDs appeared inadequate for
      full water capture on average below a depth of 0.32 m for winter wheat and below
      0.45 m for OSR. These depths compare unfavourably (for wheat) with average depths
      of 'full capture' of 0.86 m and 0.48 m, respectively, determined for three wheat
      crops and one OSR crop studied in the 1970s and 1980s, and treated as references
      here. A simple model of water uptake and yield indicated that these shortfalls in
      wheat and OSR rooting compared with the reference data might be associated with
      shortfalls of up to 3.5 t ha(-1) and 1.2 t ha(-1), respectively, in grain yields
      under water-limited conditions, as increasingly occur through climate change.
      Coupled with decreased summer rainfall, poor rooting of modern arable crops could
      explain much of the yield stagnation that has been observed on UK farms since the
      1990s. Methods of monitoring and improving rooting under commercial conditions
      are reviewed and discussed. 

PMID- 25750428
TI  - The importance of safeguarding genome integrity in germination and seed
      longevity.
AB  - Seeds are important to agriculture and conservation of plant biodiversity. In
      agriculture, seed germination performance is an important determinant of crop
      yield, in particular under adverse climatic conditions. Deterioration in seed
      quality is associated with the accumulation of cellular damage to macromolecules
      including lipids, protein, and DNA. Mechanisms that mitigate the deleterious
      cellular damage incurred in the quiescent state and in cycles of desiccation
      hydration are crucial for the maintenance of seed viability and germination
      vigour. In early-imbibing seeds, damage to the embryo genome must be repaired
      prior to initiation of cell division to minimize growth inhibition and mutation
      of genetic information. Here we review recent advances that have established
      molecular links between genome integrity and seed quality. These studies
      identified that maintenance of genome integrity is particularly important to the
      seed stage of the plant lifecycle, revealing new insight into the physiological
      roles of plant DNA repair and recombination mechanisms. The high conservation of
      DNA repair and recombination factors across plant species underlines their
      potential as promising targets for the improvement of crop performance and
      development of molecular markers for prediction of seed vigour. 

PMID- 25750429
TI  - Identifying traits for genotypic adaptation using crop models.
AB  - Genotypic adaptation involves the incorporation of novel traits in crop varieties
      so as to enhance food productivity and stability and is expected to be one of the
      most important adaptation strategies to future climate change. Simulation
      modelling can provide the basis for evaluating the biophysical potential of crop
      traits for genotypic adaptation. This review focuses on the use of models for
      assessing the potential benefits of genotypic adaptation as a response strategy
      to projected climate change impacts. Some key crop responses to the environment,
      as well as the role of models and model ensembles for assessing impacts and
      adaptation, are first reviewed. Next, the review describes crop-climate models
      can help focus the development of future-adapted crop germplasm in breeding
      programmes. While recently published modelling studies have demonstrated the
      potential of genotypic adaptation strategies and ideotype design, it is argued
      that, for model-based studies of genotypic adaptation to be used in crop
      breeding, it is critical that modelled traits are better grounded in genetic and
      physiological knowledge. To this aim, two main goals need to be pursued in future
      studies: (i) a better understanding of plant processes that limit productivity
      under future climate change; and (ii) a coupling between genetic and crop growth
      models-perhaps at the expense of the number of traits analysed. Importantly, the
      latter may imply additional complexity (and likely uncertainty) in crop modelling
      studies. Hence, appropriately constraining processes and parameters in models and
      a shift from simply quantifying uncertainty to actually quantifying robustness
      towards modelling choices are two key aspects that need to be included into
      future crop model-based analyses of genotypic adaptation. 

PMID- 25750430
TI  - The role of reactive oxygen species and nitric oxide in programmed cell death
      associated with self-incompatibility.
AB  - Successful sexual reproduction often relies on the ability of plants to recognize
      self- or genetically-related pollen and prevent pollen tube growth soon after
      germination in order to avoid self-fertilization. Angiosperms have developed
      different reproductive barriers, one of the most extended being self
      incompatibility (SI). With SI, pistils are able to reject self or genetically
      related pollen thus promoting genetic variability. There are basically two
      distinct systems of SI: gametophytic (GSI) and sporophytic (SSI) based on their
      different molecular and genetic control mechanisms. In both types of SI,
      programmed cell death (PCD) has been found to play an important role in the
      rejection of self-incompatible pollen. Although reactive oxygen species (ROS)
      were initially recognized as toxic metabolic products, in recent years, a new
      role for ROS has become apparent: the control and regulation of biological
      processes such as growth, development, response to biotic and abiotic
      environmental stimuli, and PCD. Together with ROS, nitric oxide (NO) has become
      recognized as a key regulator of PCD. PCD is an important mechanism for the
      controlled elimination of targeted cells in both animals and plants. The major
      focus of this review is to discuss how ROS and NO control male-female cross-talk
      during fertilization in order to trigger PCD in self-incompatible pollen,
      providing a highly effective way to prevent self-fertilization. 

PMID- 25750431
TI  - Myeloid HIFs are dispensable for resolution of inflammation during skeletal
      muscle regeneration.
AB  - Besides their role in cellular responses to hypoxia, hypoxia-inducible factors
      (HIFs) are involved in innate immunity and also have anti-inflammatory (M2)
      functions, such as resolution of inflammation preceding healing. Whereas the
      first steps of the inflammatory response are associated with proinflammatory (M1)
      macrophages (MPs), resolution of inflammation is associated with anti
      inflammatory MPs exhibiting an M2 phenotype. This M1 to M2 sequence is observed
      during postinjury muscle regeneration, which provides an excellent paradigm to
      study the resolution of sterile inflammation. In this study, using in vitro and
      in vivo approaches in murine models, we demonstrated that deletion of hif1a or
      hif2a in MPs has no impact on the acquisition of an M2 phenotype. Furthermore,
      using a multiscale methodological approach, we showed that muscles did not
      require macrophagic hif1a or hif2a to regenerate. These results indicate that
      macrophagic HIFs do not play a crucial role during skeletal muscle regeneration
      induced by sterile tissue damage. 

PMID- 25750432
TI  - IFN-gamma priming of macrophages represses a part of the inflammatory program and
      attenuates neutrophil recruitment.
AB  - Macrophages form a heterogeneous population of immune cells, which is critical
      for both the initiation and resolution of inflammation. They can be skewed to a
      proinflammatory subtype by the Th1 cytokine IFN-gamma and further activated with
      TLR triggers, such as LPS. In this work, we investigated the effects of IFN-gamma
      priming on LPS-induced gene expression in primary mouse macrophages.
      Surprisingly, we found that IFN-gamma priming represses a subset of LPS-induced
      genes, particularly genes involved in cellular movement and leukocyte
      recruitment. We found STAT1-binding motifs enriched in the promoters of these
      repressed genes. Furthermore, in the absence of STAT1, affected genes are
      derepressed. We also observed epigenetic remodeling by IFN-gamma priming on
      enhancer or promoter sites of repressed genes, which resulted in less NF-kappaB
      p65 recruitment to these sites without effects on global NF-kappaB activation.
      Finally, the epigenetic and transcriptional changes induced by IFN-gamma priming
      reduce neutrophil recruitment in vitro and in vivo. Our data show that IFN-gamma
      priming changes the inflammatory repertoire of macrophages, leading to a change
      in neutrophil recruitment to inflammatory sites. 

PMID- 25750433
TI  - TCAIM decreases T cell priming capacity of dendritic cells by inhibiting TLR
      induced Ca2+ influx and IL-2 production.
AB  - We previously showed that the T cell activation inhibitor, mitochondrial (Tcaim)
      is highly expressed in grafts of tolerance-developing transplant recipients and
      that the encoded protein is localized within mitochondria. In this study, we show
      that CD11c(+) dendritic cells (DCs), as main producers of TCAIM, downregulate
      Tcaim expression after LPS stimulation or in vivo alloantigen challenge. LPS
      stimulated TCAIM-overexpressing bone marrow-derived DC (BMDCs) have a reduced
      capacity to induce proliferation of and cytokine expression by cocultured
      allogeneic T cells; this is not due to diminished upregulation of MHC or
      costimulatory molecules. Transcriptional profiling also revealed normal LPS
      mediated upregulation of the majority of genes involved in TLR signaling.
      However, TCAIM BMDCs did not induce Il2 mRNA expression upon LPS stimulation in
      comparison with Control-BMDCs. In addition, TCAIM overexpression abolished LPS
      mediated Ca(2+) influx and mitochondrial reactive oxygen species formation.
      Addition of IL-2 to BMDC-T cell cocultures restored the priming capacity of TCAIM
      BMDCs for cocultured allogeneic CD8(+) T cells. Furthermore, BMDCs of IL-2
      deficient mice showed similarly abolished LPS-induced T cell priming as TCAIM
      overexpressing wild type BMDCs. Thus, TCAIM interferes with TLR4 signaling in
      BMDCs and subsequently impairs their T cell priming capacity, which supports its
      role for tolerance induction. 

PMID- 25750434
TI  - RHAMM deficiency disrupts folliculogenesis resulting in female hypofertility.
AB  - The postnatal mammalian ovary contains the primary follicles, each comprising an
      immature oocyte surrounded by a layer of somatic granulosa cells. Oocytes reach
      meiotic and developmental competence via folliculogenesis. During this process,
      the granulosa cells proliferate massively around the oocyte, form an extensive
      extracellular matrix (ECM) and differentiate into cumulus cells. As the ECM
      component hyaluronic acid (HA) is thought to form the backbone of the oocyte
      granulosa cell complex, we deleted the relevant domain of the Receptor for HA
      Mediated Motility (RHAMM) gene in the mouse. This resulted in folliculogenesis
      defects and female hypofertility, although HA-induced signalling was not
      affected. We report that wild-type RHAMM localises at the mitotic spindle of
      granulosa cells, surrounding the oocyte. Deletion of the RHAMM C-terminus in vivo
      abolishes its spindle association, resulting in impaired spindle orientation in
      the dividing granulosa cells, folliculogenesis defects and subsequent female
      hypofertility. These data reveal the first identified physiological function for
      RHAMM, during oogenesis, and the importance of this spindle-associated function
      for female fertility. 

PMID- 25750435
TI  - Efficient retina formation requires suppression of both Activin and BMP signaling
      pathways in pluripotent cells.
AB  - Retina formation requires the correct spatiotemporal patterning of key regulatory
      factors. While it is known that repression of several signaling pathways lead to
      specification of retinal fates, addition of only Noggin, a known BMP antagonist,
      can convert pluripotent Xenopus laevis animal cap cells to functional retinal
      cells. The aim of this study is to determine the intracellular molecular events
      that occur during this conversion. Surprisingly, blocking BMP signaling alone
      failed to mimic Noggin treatment. Overexpressing Noggin in pluripotent cells
      resulted in a concentration-dependent suppression of both Smad1 and Smad2
      phosphorylation, which act downstream of BMP and Activin signaling, respectively.
      This caused a decrease in downstream targets: endothelial marker, xk81, and
      mesodermal marker, xbra. We treated pluripotent cells with dominant-negative
      receptors or the chemical inhibitors, dorsomorphin and SB431542, which each
      target either the BMP or Activin signaling pathway. We determined the effect of
      these treatments on retina formation using the Animal Cap Transplant (ACT) assay;
      in which treated pluripotent cells were transplanted into the eye field of host
      embryos. We found that inhibition of Activin signaling, in the presence of BMP
      signaling inhibition, promotes efficient retinal specification in Xenopus tissue,
      mimicking the affect of adding Noggin alone. In whole embryos, we found that the
      eye field marker, rax, expanded when adding both dominant-negative Smad1 and
      Smad2, as did treating the cells with both dorsomorphin and SB431542. Future
      studies could translate these findings to a mammalian culture assay, in order to
      more efficiently produce retinal cells in culture. 

PMID- 25750437
TI  - The effect of water temperature on routine swimming behaviour of new born guppies
      (Poecilia reticulata).
AB  - Guppies have successfully established populations in places with thermal regimes
      very different from the Tropical conditions in their native range. This indicates
      a remarkable capacity for thermal adaptation. Given their vulnerability to
      predation as juveniles, acute changes in temperature, which can alter predator
      prey relationships, can impact juvenile survival and have amplified consequences
      at the population level. To understand how temperature may impact juvenile
      survival and gain insight into their success as an invasive species, we
      researched the effect of acute temperature changes on the routine swimming
      behaviour of juvenile guppies. Using a novel 3-dimensional tracking technique, we
      calculated 4 routine swimming parameters, speed, depth, and variation in speed or
      depth, at 6 different test temperatures (17, 20, 23, 26, 29, or 32 degrees C).
      These temperatures cover their natural thermal range and also extended past it in
      order to include upper and lower thermal limits. Using model selection, we found
      that body length and temperature had a significant positive relationship with
      speed. Variation in speed decreased with rising temperatures and fish swam
      slightly closer to the bottom at higher temperatures. All juveniles increased
      variation in depth at higher temperatures, though larger individuals maintained
      slightly more consistent depths. Our results indicate that guppies have a large
      thermal range and show substantial plasticity in routine swimming behaviours,
      which may account for their success as an invasive species. 

PMID- 25750436
TI  - MASTL promotes cyclin B1 destruction by enforcing Cdc20-independent binding of
      cyclin B1 to the APC/C.
AB  - When cells enter mitosis, the anaphase-promoting complex/cyclosome (APC/C) is
      activated by phosphorylation and binding of Cdc20. The RXXL destruction box (D
      box) of cyclin B1 only binds Cdc20 after release of the spindle checkpoint in
      metaphase, initiating cyclin B1 ubiquitination upon chromosome bi-orientation.
      However, we found that cyclin B1, through Cdk1 and Cks, is targeted to the
      phosphorylated APC/C(Cdc20) at the start of prometaphase, when the spindle
      checkpoint is still active. Here, we show that MASTL is essential for cyclin B1
      recruitment to the mitotic APC/C and that this occurs entirely independently of
      Cdc20. Importantly, MASTL-directed binding of cyclin B1 to spindle checkpoint
      inhibited APC/C(Cdc20) critically supports efficient cyclin B1 destruction after
      checkpoint release. A high incidence of anaphase bridges observed in response to
      MASTL RNAi may result from cyclin B1 remaining after securin destruction, which
      is insufficient to keep MASTL-depleted cells in mitosis but delays the activation
      of separase. 

PMID- 25750438
TI  - A single and rapid calcium wave at egg activation in Drosophila.
AB  - Activation is an essential process that accompanies fertilisation in all animals
      and heralds major cellular changes, most notably, resumption of the cell cycle.
      While activation involves wave-like oscillations in intracellular Ca(2+)
      concentration in mammals, ascidians and polychaete worms and a single Ca(2+) peak
      in fish and frogs, in insects, such as Drosophila, to date, it has not been shown
      what changes in intracellular Ca(2+) levels occur. Here, we utilise ratiometric
      imaging of Ca(2+) indicator dyes and genetically encoded Ca(2+) indicator
      proteins to identify and characterise a single, rapid, transient wave of Ca(2+)
      in the Drosophila egg at activation. Using genetic tools, physical manipulation
      and pharmacological treatments we demonstrate that the propagation of the Ca(2+)
      wave requires an intact actin cytoskeleton and an increase in intracellular
      Ca(2+) can be uncoupled from egg swelling, but not from progression of the cell
      cycle. We further show that mechanical pressure alone is not sufficient to
      initiate a Ca(2+) wave. We also find that processing bodies, sites of mRNA decay
      and translational regulation, become dispersed following the Ca(2+) transient.
      Based on this data we propose the following model for egg activation in
      Drosophila: exposure to lateral oviduct fluid initiates an increase in
      intracellular Ca(2+) at the egg posterior via osmotic swelling, possibly through
      mechano-sensitive Ca(2+) channels; a single Ca(2+) wave then propagates in an
      actin dependent manner; this Ca(2+) wave co-ordinates key developmental events
      including resumption of the cell cycle and initiation of translation of mRNAs
      such as bicoid. 

PMID- 25750439
TI  - Analytic P-value calculation for the higher criticism test in finite d problems.
AB  - The higher criticism is effective for testing a joint null hypothesis against a
      sparse alternative, e.g., for testing the effect of a gene or a genetic pathway
      that consists of d genetic markers. Accurate p-value calculations for the higher
      criticism based on the asymptotic distribution require a very large d, which is
      not the case for the number of genetic variants in a gene or a pathway. In this
      paper we propose an analytic method that accurately computes the p-value of the
      higher criticism test for finite d problems. Unlike previous treatments, this
      method does not rely on asymptotics in d or simulation, and is exact for
      arbitrary d when the test statistics are normally distributed. The method is
      particularly computationally advantageous when d is not large. We illustrate the
      proposed method with a case-control genome-wide association study of lung cancer
      and compare its power to competing methods through simulations.

PMID- 25750440
TI  - Trends in veterinary medicine in Canada.

PMID- 25750441
TI  - Ethical question of the month--March 2015.

PMID- 25750442
TI  - Perianal neuroendocrine tumor with suspected lymph node metastasis causing
      colonic compression and subsequent megacolon.
AB  - An 8-year-old spayed female domestic shorthair cat was presented with a 4- to 5
      month history of a progressively growing mass above her anus and an inability to
      defecate for 3 to 4 wk. External perianal and internal regional masses were
      subsequently identified and diagnosed as tumors of neuroendocrine origin through
      surgical excision and histopathologic evaluation. The cat was treated with 2
      courses of chemotherapy and radiation therapy. 

PMID- 25750443
TI  - Urticaria pigmentosa-like disease in a dog.
AB  - Urticaria pigmentosa is a rare dermatologic syndrome in humans, cats, and dogs.
      This report documents a case of canine urticaria pigmentosa-like disease with
      unusual features and no C-kit mutation. 

PMID- 25750444
TI  - Optic neuropathy in a herd of beef cattle in Alberta associated with consumption
      of moldy corn.
AB  - A group of beef cattle in eastern Alberta was investigated due to sudden onset of
      blindness after grazing on standing corn in mid-winter. Fumonisin-producing
      Fusarium spp. were isolated from the corn. Blindness was due to an optic nerve
      degeneration suspected to be secondary to fumonisin mycotoxin. 

PMID- 25750445
TI  - Bilateral renal dysplasia, hydronephrosis, and hydroureter in a septic neonatal
      foal.
AB  - A Canadian warmblood foal treated for septic polyarthritis was diagnosed with
      bilateral congenital renal dysplasia, hydronephrosis, and hydroureter at 2 weeks
      of age based on abdominal ultrasound and postmortem examination. Intermittent
      abdominal pain throughout the course of treatment was attributed to
      hydronephrosis and hydroureter. 

PMID- 25750446
TI  - The use of computed tomography to diagnose chronic shoulder arthritis in an
      American white pelican (Pelecanus erythrorhynchos).
AB  - An American white pelican was presented with a complete left wing droop and no
      abnormal findings on conventional radiography. Computed tomography was used to
      diagnose chronic shoulder arthritis as a sequela to a suspected traumatic
      compressive fracture. This is the first case report to describe use of computed
      tomography to evaluate the avian shoulder joint. 

PMID- 25750448
TI  - Mucopolysaccharidosis type VI in a juvenile miniature schnauzer dog with
      concurrent hypertriglyceridemia, necrotizing pancreatitis, and diabetic
      ketoacidosis.
AB  - A 7-month-old, neutered male miniature schnauzer dog with a history of
      cryptorchidism and umbilical hernia was referred for diabetic ketoacidosis.
      Clinical evaluation revealed stunted growth, skeletal abnormalities,
      hypertriglyceridemia, diabetic ketoacidosis, and acute necrotizing pancreatitis.
      Further testing was diagnostic for mucopolysaccharidosis type VI causing the
      stunted growth and skeletal deformities, but no connection between
      mucopolysaccharidosis type VI, hypertriglyceridemia, and pancreatic diseases was
      found. 

PMID- 25750447
TI  - Pulmonary Echinococcus multilocularis metastasis in a dog.
AB  - A young adult Labrador retriever dog was presented for surgical debulking of
      hepatic alveolar echinococcosis. Computed tomography detected hepatomegaly with
      multiple large cavitary masses with extension of tissue from a lesion wall into
      the caudal vena cava and numerous nodules in all lung lobes. Following
      euthanasia, histology confirmed parasitic vesicles with granulomatous reaction in
      all lesions, and polymerase chain reaction (PCR) established the causative agent
      to be Echinococcus multilocularis. This report is the first to present imaging
      features of pulmonary E. multilocularis granulomata in a dog. 

PMID- 25750449
TI  - Suspected primary hematomyelia in 3 dogs.
AB  - Primary hematomyelia refers to hemorrhage occurring within the spinal cord
      without an identifiable etiology. Clinical signs, magnetic resonance imaging
      characteristics, and histopathological findings are described. Diagnosis was made
      through histological analysis and rule-outs for underlying factors. Following
      removal of the hematoma, neurologic deficits improved, although some residual
      deficits persisted. 

PMID- 25750450
TI  - Associations among Haemophilus parasuis, Mycoplasma hyorhinis, and porcine
      reproductive and respiratory syndrome virus infections in pigs with
      polyserositis.
AB  - The objective of this study was to determine the associations among Haemophilus
      parasuis, Mycoplasma hyorhinis, and porcine reproductive and respiratory syndrome
      (PRRS) virus (EU-field strain) infections in 95 pigs with polyserositis. A
      significant association between H. parasuis and M. hyorhinis was identified. H.
      parasuis and M. hyorhinis were significantly more often detected in PRRS virus
      positive pigs. 

PMID- 25750451
TI  - Foramen magnum decompression surgery in 23 Chiari-like malformation patients 2007
      2010: outcomes and owner survey results.
AB  - Chiari-like malformation (CLM) with syringomyelia (SM) in dogs is particularly
      prominent in the Cavalier King Charles spaniel breed, but has also been reported
      in several other small breed dogs. Over a period of 3 years, 23 canine patients
      were treated surgically for CLM-SM. Surgery consisted of foramen magnum
      decompression, durotomy, duraplasty, and free autogenous adipose tissue grafting
      (fat graft). All patients were re-evaluated clinically at least 1 month after
      surgery and some up to 3 years after surgery. Improvement was noted on all
      clinical evaluations. A questionnaire was mailed to all 23 owners after a period
      of at least 1 year after surgery. Seventeen surveys were returned. No patient has
      required additional surgery to date, 94% (16/17) had some improvement in quality
      of life after surgery, and none were judged to deteriorate to less than the pre
      surgical status. The authors conclude that this surgical procedure, combined with
      medical therapy, resulted in favorable long-term outcomes.

PMID- 25750452
TI  - Mandibulectomy for treatment of fractures associated with severe periodontal
      disease.
AB  - Six cases of mandibular fractures associated with severe periodontal disease that
      had been treated by mandibulectomy, due to intense bone loss, were evaluated
      retrospectively. The dogs were mainly older, small breed dogs that had suffered a
      traumatic event. Four dogs had a bilateral mandibulectomy and 2 a unilateral
      mandibulectomy. 

PMID- 25750453
TI  - Periodontology: an overview of alveolar bone expansion.

PMID- 25750454
TI  - Diagnostic ophthalmology.

PMID- 25750455
TI  - Low hanging fruit: the foregone revenue of elective surgeries.

PMID- 25750457
TI  - Lipid Analysis of Airway Epithelial Cells for Studying Respiratory Diseases.
AB  - Airway epithelial cells play an important role in the pathogenesis of
      inflammatory lung diseases such as asthma, cystic fibrosis and COPD. Studies
      concerning the function of the lipid metabolism of the airway epithelium are so
      far based only on the detection of lipids by immunohistochemistry but
      quantitative analyses have not been performed. Although recent advances in mass
      spectrometry have allowed to identify a variety of lipid classes simultaneously
      in isolated tissue samples, up until now, these methods were not suitable to
      analyze lipids in the airway epithelium. To determine all major lipid classes in
      airway epithelial cells, we used an LC-MS-based approach that can easily be
      combined with the specific isolation procedure to obtain epithelial cells. We
      tested the suitability of this method with a mouse model of experimental asthma.
      In response to allergen challenge, perturbations in the sphingolipids were
      detected, which led to increased levels of ceramides. We expanded the scope of
      this approach analysing human bronchus samples without pathological findings of
      adenocarcinoma patients. For the human lung epithelium an unusual lipid class
      distribution was found in which ceramide was the predominant sphingolipid. In
      summary, we show that disease progression and lipid metabolism perturbation can
      be monitored in animal models and that the method can be used for the analysis of
      clinical samples.

PMID- 25750458
TI  - Molecular structure studies of (1S,2S)-2-benzyl-2,3-dihydro-2-(1H-inden-2-yl)-1H
      inden-1-ol.
AB  - The single enantiomer (1S,2S)-2-benzyl-2,3-dihydro-2-(1H-inden-2-yl)-1H-inden-1
      ol (2), has recently been synthesized and isolated from its corresponding
      diastereoisomer (1). The molecular and crystal structures of this novel compound
      have been fully analyzed. The relative and absolute configurations have been
      determined by using a combination of analytical tools including X-ray
      crystallography, X-ray Powder Diffraction (XRPD) analysis and Nuclear Magnetic
      Resonance (NMR) spectroscopy.

PMID- 25750456
TI  - Clinical Glycomics Employing Graphitized Carbon Liquid Chromatography-Mass
      Spectrometry.
AB  - Glycoconjugates and free glycan are involved in a variety of biological processes
      such as cell-cell interaction and cell trafficking. Alterations in the complex
      glycosylation machinery have been correlated with various pathological processes
      including cancer progression and metastasis. Mass Spectrometry (MS) has evolved
      as one of the most powerful tools in glycomics and glycoproteomics and in
      combination with porous graphitized carbon-liquid chromatography (PGC-LC) it is a
      versatile and sensitive technique for the analysis of glycans and to some extent
      also glycopeptides. PGC-LC-ESI-MS analysis is characterized by a high isomer
      separation power enabling a specific glycan compound analysis on the level of
      individual structures. This allows the investigation of the biological relevance
      of particular glycan structures and glycan features. Consequently, this strategy
      is a very powerful technique suitable for clinical research, such as cancer
      biomarker discovery, as well as in-depth analysis of recombinant glycoproteins.
      In this review, we will focus on how PGC in conjunction with MS detection can
      deliver specific structural information for clinical research on protein-bound N
      glycans and mucin-type O-glycans. In addition, we will briefly review PGC
      analysis approaches for glycopeptides, glycosaminoglycans (GAGs) and human milk
      oligosaccharides (HMOs). The presented applications cover systems that vary
      vastly with regard to complexity such as purified glycoproteins, cells, tissue or
      body fluids revealing specific glycosylation changes associated with various
      biological processes including cancer and inflammation.

PMID- 25750459
TI  - Measuring Returns to Hospital Care: Evidence from Ambulance Referral Patterns.
AB  - Medicare spending exceeds 4% of GDP in the US each year, and there are concerns
      that moral hazard problems have led to overspending. This paper considers whether
      hospitals that treat patients more aggressively and receive higher payments from
      Medicare improve health outcomes for their patients. An innovation is a new lens
      to compare hospital performance for emergency patients: plausibly exogenous
      variation in ambulance-company assignment among patients who live near one
      another. Using Medicare data from 2002-2010, we show that ambulance company
      assignment importantly affects hospital choice for patients in the same ZIP code.
      Using data for New York State from 2000-2006 that matches exact patient addresses
      to hospital discharge records, we show that patients who live very near each
      other but on either side of ambulance service area boundaries go to different
      types of hospitals. Both identification strategies show that higher-cost
      hospitals achieve better patient outcomes for a variety of emergency conditions.
      Using our Medicare sample, the estimates imply that a one standard deviation
      increase in Medicare reimbursement leads to a 4 percentage point reduction in
      mortality (10% compared to the mean). Taking into account one-year spending after
      the health shock, the implied cost per at least one year of life saved is
      approximately $80,000. These results are found across different types of
      hospitals and patients, as well across both identification strategies.

PMID- 25750460
TI  - The characters of Palaeozoic jawed vertebrates.
AB  - Newly discovered fossils from the Silurian and Devonian periods are beginning to
      challenge embedded perceptions about the origin and early diversification of
      jawed vertebrates (gnathostomes). Nevertheless, an explicit cladistic framework
      for the relationships of these fossils relative to the principal crown lineages
      of the jawed vertebrates (osteichthyans: bony fishes and tetrapods;
      chondrichthyans: sharks, batoids, and chimaeras) remains elusive. We critically
      review the systematics and character distributions of early gnathostomes and
      provide a clearly stated hierarchy of synapomorphies covering the jaw-bearing
      stem gnathostomes and osteichthyan and chondrichthyan stem groups. We show that
      character lists, designed to support the monophyly of putative groups, tend to
      overstate their strength and lack cladistic corroboration. By contrast,
      synapomorphic hierarchies are more open to refutation and must explicitly
      confront conflicting evidence. Our proposed synapomorphy scheme is used to
      evaluate the status of the problematic fossil groups Acanthodii and Placodermi,
      and suggest profitable avenues for future research. We interpret placoderms as a
      paraphyletic array of stem-group gnathostomes, and suggest what we regard as two
      equally plausible placements of acanthodians: exclusively on the chondrichthyan
      stem, or distributed on both the chondrichthyan and osteichthyan stems.

PMID- 25750461
TI  - Insights into copper coordination in the EcoRI-DNA complex by ESR spectroscopy.
AB  - The EcoRI restriction endonuclease requires one divalent metal ion in each of two
      symmetrical and identical catalytic sites to catalyse double-strand DNA cleavage.
      Recently, we showed that Cu2+ binds outside the catalytic sites to a pair of new
      sites at H114 in each sub-unit, and inhibits Mg2+ -catalysed DNA cleavage. In
      order to provide more detailed structural information on this new metal ion
      binding site, we performed W-band (~94 GHz) and X-band (~9.5 GHz) electron spin
      resonance spectroscopic measurements on the EcoRI-DNA-(Cu2+ )2 complex. Cu2+
      binding results in two distinct components with different gzz and Azz values. X
      band electron spin echo envelope modulation results indicate that both components
      arise from a Cu2+ coordinated to histidine. This observation is further confirmed
      by the hyperfine sub-level correlation results. W-band electron nuclear double
      resonance spectra provide evidence for equatorial coordination of water molecules
      to the Cu2+ ions.

PMID- 25750462
TI  - Bi-national Social Networks and Assimilation: A Test of the Importance of
      Transnationalism.
AB  - While the concept of transnationalism has gained widespread popularity among
      scholars as a way to describe immigrants' long-term maintenance of cross-border
      ties to their origin communities, critics have argued that the overall proportion
      of immigrants who engage in transnational behavior is low and that, as a result,
      transnationalism has little sustained effect on the process of immigrant
      adaptation and assimilation. In this paper, we argue that a key shortcoming in
      the current empirical debate on transnationalism is the lack of data on the
      social networks that connect migrants to each other and to non-migrants in
      communities of origin. To address this shortcoming, our analysis uses unique bi
      national data on the social network connecting an immigrant sending community in
      Guanajuato, Mexico, to two destination areas in the United States. We test for
      the effect of respondents' positions in cross-border networks on their migration
      intentions and attitudes towards the United States using data on the opinions of
      their peers, their participation in cross border and local communication
      networks, and their structural position in the network. The results indicate
      qualified empirical support for a network-based model of transnationalism; in the
      U.S. sample we find evidence of network clustering consistent with peer effects,
      while in the Mexican sample we find evidence of the importance of cross-border
      communication with friends.

PMID- 25750463
TI  - Fast and Adaptive Sparse Precision Matrix Estimation in High Dimensions.
AB  - This paper proposes a new method for estimating sparse precision matrices in the
      high dimensional setting. It has been popular to study fast computation and
      adaptive procedures for this problem. We propose a novel approach, called Sparse
      Column-wise Inverse Operator, to address these two issues. We analyze an adaptive
      procedure based on cross validation, and establish its convergence rate under the
      Frobenius norm. The convergence rates under other matrix norms are also
      established. This method also enjoys the advantage of fast computation for large
      scale problems, via a coordinate descent algorithm. Numerical merits are
      illustrated using both simulated and real datasets. In particular, it performs
      favorably on an HIV brain tissue dataset and an ADHD resting-state fMRI dataset.

PMID- 25750464
TI  - The New Immigrant Survey and Research on American Stratification.

PMID- 25750465
TI  - Orthographic and semantic processing in young readers.
AB  - This investigation examined orthographic and semantic processing during reading
      acquisition. Children in first through fourth grade were presented with a target
      word and two response alternatives, and were asked to identify the semantic
      match. Words were presented in four conditions: an exact match and unrelated foil
      (STONE - STONE - EARS), an exact match and an orthographic neighbor foil (STONE -
      STONE - STOVE), a synonym match and an unrelated foil (STONE - ROCK - EARS), and
      a synonym match and an orthographic neighbor foil (STONE - ROCK - STOVE).
      Accuracy and reaction time results suggest that orthographic and semantic
      processing follow a two-step acquisition pattern. First, the orthographic
      component of reading develops quickly, however, forming strong conceptual links
      from orthographic to semantic representations follows a protracted trajectory,
      which matures between the third and fourth grade. These results are consistent
      with research that suggests younger children rely on more concrete, perceptual
      systems and then transition to more flexible, abstract cognition.

PMID- 25750466
TI  - Academic discourse: Dissociating standardized and conversational measures of
      language proficiency in bilingual kindergarteners.
AB  - This study examined the relationship between performance on standardized measures
      of language proficiency and conversational measures of the same features used in
      academic discourse among 24 monolingual and 25 bilingual kindergarteners.
      Academic discourse performance was considered for both its linguistic and its
      genre features in two discourse forms: narrative and explanation. Bilinguals
      performed more poorly than monolinguals on standardized measures of language
      proficiency, yet they performed similarly to monolinguals in the discourse-based
      linguistic and genre features. Moreover, genre features were more strongly
      related to linguistic features assessed through discourse than to standardized
      tests of these same features. These findings indicate that standardized measures
      of language proficiency underrepresent the abilities of bilingual children and
      that children's second language proficiency may be more accurately reflected in
      conversation.

PMID- 25750467
TI  - School Choice in London and Paris - A Comparison of Middle-class Strategies.
AB  - Education is one major public service in which quasi-markets and other choice
      based mechanisms are now established methods of delivery. The types of school
      people choose, and the extent to which their choices are realized, have a
      fundamental impact on the outcomes of any mechanism of school choice. In this
      article, we provide a comparative analysis of the school choice strategies of
      middle-class families in London and Paris. We draw on approximately 200 in-depth
      interviews carried out across the two cities. This enables us to investigate the
      extent to which middle-class school choice strategies transcend the institutional
      context provided by both the local (state and private) schools market and
      national education policy in England and France. We discuss these findings in the
      context of current school choice policy and consider their implications for
      future policy design.

PMID- 25750468
TI  - "?Como estas?" "I'm good." Conversational code-switching is related to profiles
      of expressive and receptive proficiency in Spanish-English bilingual toddlers.
AB  - Relations between bilingual children's patterns of conversational code-switching
      (responding to one language with another), the balance of their dual language
      input, and their expressive and receptive proficiency in two languages were
      examined in 115 21/2-year-old simultaneous Spanish-English bilinguals in the U.S.
      Children were more likely to code-switch in response to Spanish than English.
      Children's expressive vocabulary scores were higher in English than in Spanish,
      while their English and Spanish receptive language scores were not different.
      Analyses of subgroups of children with different but consistent patterns of code
      switching confirmed that children who code-switched to English showed greater
      English skills, specifically in the expressive domain. Children who did not code
      switch were more balanced bilinguals in both expressive and receptive skills.
      Children with other code-switching patterns showed still different profiles of
      dual language expressive and receptive proficiency. These findings reveal that
      some, but not all, bilingual children show different profiles of expressive and
      receptive skill in their two languages and that these proficiency profiles are
      related to their language choices in conversation.

PMID- 25750469
TI  - The Implications of Grandparent Coresidence for Economic Hardship among Children
      in Mother-Only Families.
AB  - Estimates suggest that more than 6 million children live with at least one
      grandparent. Despite evidence establishing the growing prevalence of this
      arrangement, limited research has focused on estimating the implications of co
      residence for the economic well-being of grandchildren. Using data from the 2001
      panel of the Survey of Income and Program Participation, this paper examines
      levels of financial hardship among a particularly vulnerable group of children -
      those living in mother-only families. Findings suggest that children living in
      mother-only families that include a grandparent are substantially less likely to
      be living below or near the poverty level, compared to children living in mother
      only families without a grandparent present. The financial security of children
      in these three-generation households is enhanced through significant economic
      contributions of the grandparents, and from household receipt of a wide range of
      financial resources, including means-tested cash transfers and other income such
      as Social Security.

PMID- 25750470
TI  - Techniques to derive geometries for image-based Eulerian computations.
AB  - PURPOSE: The performance of three frequently used level set-based segmentation
      methods is examined for the purpose of defining features and boundary conditions
      for image-based Eulerian fluid and solid mechanics models. The focus of the
      evaluation is to identify an approach that produces the best geometric
      representation from a computational fluid/solid modeling point of view. In
      particular, extraction of geometries from a wide variety of imaging modalities
      and noise intensities, to supply to an immersed boundary approach, is targeted.
      DESIGN/METHODOLOGY/APPROACH: Two- and three-dimensional images, acquired from
      optical, X-ray CT, and ultrasound imaging modalities, are segmented with active
      contours, k-means, and adaptive clustering methods. Segmentation contours are
      converted to level sets and smoothed as necessary for use in fluid/solid
      simulations. Results produced by the three approaches are compared visually and
      with contrast ratio, signal-to-noise ratio, and contrast-to-noise ratio measures.
      FINDINGS: While the active contours method possesses built-in smoothing and
      regularization and produces continuous contours, the clustering methods (k-means
      and adaptive clustering) produce discrete (pixelated) contours that require
      smoothing using speckle-reducing anisotropic diffusion (SRAD). Thus, for images
      with high contrast and low to moderate noise, active contours are generally
      preferable. However, adaptive clustering is found to be far superior to the other
      two methods for images possessing high levels of noise and global intensity
      variations, due to its more sophisticated use of local pixel/voxel intensity
      statistics. ORIGINALITY/VALUE: It is often difficult to know a priori which
      segmentation will perform best for a given image type, particularly when
      geometric modeling is the ultimate goal. This work offers insight to the
      algorithm selection process, as well as outlining a practical framework for
      generating useful geometric surfaces in an Eulerian setting.

PMID- 25750471
TI  - Associations between the prenatal environment and cardiovascular risk factors in
      adolescent girls: Internalizing and externalizing behavior symptoms as mediators.
AB  - This longitudinal study examines links among adolescent internalizing and
      externalizing symptoms, the prenatal environment (e.g., nicotine exposure) and
      pre/perinatal maternal health, and cardiovascular risk factors. Girls (N=262)
      ages 11-17 reported internalizing and externalizing behaviors and mothers
      reported about the prenatal environment and maternal health during and 3 months
      post-pregnancy. Adolescent cardiovascular risk included adiposity, smoking, blood
      pressure, and salivary C-reactive protein. Internalizing symptoms mediated
      relations between prenatal exposures/maternal health and adiposity; externalizing
      symptoms mediated relations between prenatal exposures and adolescent smoking.
      Healthcare providers who attend to internalizing and externalizing symptoms in
      girls may ultimately influence cardiovascular health, especially among those with
      pre/perinatal risk factors.

PMID- 25750472
TI  - A Preliminary Study of Depressive Symptoms in Mothers of 3-Year-Old Prematurely
      Born Children.
AB  - This exploratory study examined the effects of maternal depressive symptoms on
      mothers' perceptions of their 3-year-old prematurely born children, interactive
      behaviors, and child outcomes. Mother and child interactive behaviors were coded
      from naturalistic observations in their homes. Education and marital status were
      found to be significantly related to maternal depressive symptoms. Factor
      analyses were conducted to determine the most prominent behaviors related to
      maternal depressive symptoms. In a small sample of mothers, the quality of the
      maternal-child relationship was negatively affected by elevated depressive
      symptoms. Mothers of prematurely born children may report depressive symptoms
      that continue into early childhood.

PMID- 25750473
TI  - Is There a "Workable" Race-Neutral Alternative to Affirmative Action in College
      Admissions?
AB  - The 2013 decision by the U.S. Supreme Court in the Fisher v. University of Texas
      at Austin case clarified when and how it is legally permissible for universities
      to use an applicant's race or ethnicity in its admissions decisions. The court
      concluded that such use is permissible when "no workable race-neutral
      alternatives would produce the educational benefits of diversity." This paper
      shows that replacing traditional affirmative action with a system that uses an
      applicant's predicted likelihood of being an underrepresented racial minority as
      a proxy for the applicant's actual minority status can yield an admitted class
      that has a lower predicted grade point average and likelihood of graduating than
      the class that would have been admitted using traditional affirmative action.
      This result suggests that race-neutral alternatives may not be "workable" from
      the university's perspective.

PMID- 25750474
TI  - The role of nucleating agents in high-pressure-induced gamma crystallization in
      isotactic polypropylene.
AB  - Nucleation of the gamma-form in isotactic polypropylene (PP) under high pressure
      was investigated. Three nucleating agents were used to nucleate crystallization
      of PP under atmospheric pressure: commercial Hyperform HPN-20E from Milliken
      Chemical, poly(tetrafluoroethylene) particles nucleating the alpha-form, and
      calcium pimelate nucleating the beta-form. Crystallization of neat PP and PP with
      addition of 0.2 wt% of the nucleating agents was studied. Specimens were either
      kept at 200  degrees C under pressure of 200 MPa for time ranging from 2 min to 4
      h or for 15 min under pressure ranging from 1.3 to 300 MPa. After cooling to
      ambient temperature and releasing the pressure, the specimens were analyzed by
      DSC, WAXD, and PLM to have an insight into the structure and to determine a
      crystallinity level and contents of crystallographic forms. Both alpha-nucleating
      agents strongly nucleated crystallization of PP under high pressure in the gamma
      form, whereas the beta-nucleating agent had only a slight effect. The results
      show the possibility to use nucleating agents to nucleate the gamma-form of PP
      under high pressure.

PMID- 25750475
TI  - Unsupported or Turned Against: Understanding How Two Types of Negative Social
      Reactions to Sexual Assault Relate to Post-Assault Outcomes.
AB  - Social reactions to disclosures of sexual assault have significant effects on
      women's post-assault outcomes (see Ullman, 2010, for a review). The Social
      Reactions Questionnaire (SRQ; Ullman, 2000) measures these reactions (as reported
      by survivors) and aggregates them into positive and negative scales. However,
      studies indicate that only some "negative" reactions have a negative valence for
      survivors whereas others produce a mixed (positive and negative) valence. The
      current study compares a one-primary-factor model of "negative reactions" to a
      model with two primary factors that we have labeled "turning against" and
      "unsupportive acknowledgement." Results showed that although one primary factor
      was plausible, two primary factors provided a better fit to the data. To assess
      the discriminant validity of the two factors, we performed regressions predicting
      social support, psychological adjustment, and coping behaviors. Analyses
      supported the hypotheses that reactions of being turned against were related to
      social withdrawal, increased self-blame, and decreased sexual assertiveness
      whereas reactions of unsupportive acknowledgment were related to both adaptive
      and maladaptive coping. Against predictions, depression and PTSD were more
      related to receiving unsupportive acknowledgment than to receiving turning
      against reactions. Implications for interventions and research are discussed.
      Importantly, almost all women (94%) in our sample received reactions that
      acknowledged that an assault occurred but failed to provide support, and this
      lack of support was associated with worse coping than even more hostile reactions
      such as being blamed or stigmatized. Therefore, there seems a great need for
      effective programs to train community members to respond to survivors with the
      kind of emotional and tangible support that promotes better outcomes.

PMID- 25750476
TI  - Evaluation of ergosterol content in the air of various environments.
AB  - The aim of the study was to compare the content of ergosterol in different
      microorganisms (bacteria, yeasts and moulds) isolated from the air as well as in
      six species of moulds in their different morphological forms-live mycelium, dead
      mycelium, and spores. Evaluation of the level of mould contamination of the air
      in various places using culture method and ergosterol determination was also
      performed. The analysis of ergosterol was carried out by gas chromatography
      equipped with flame ionisation detector. For evaluation of the results, analysis
      of variance and multiple comparison test were used. The quantity of ergosterol in
      the spores of various species of mould was in the range 1.9-9.4 pg/spore. The
      presence of yeasts and bacteria in the air does not significantly affect
      ergosterol concentration, in view of the low content of that sterol in their
      cells (max. 0.009 pg/cell for bacteria and 0.39 pg/cell for yeast). An ergosterol
      concentration above 1 ng per m3 can be considered an indicator of excessive mould
      contamination of indoor air. Based on determination of ergosterol in the air of
      mouldy rooms the result obtained may be compared with the culture method, due to
      the 1,000 times higher concentration of ergosterol in the mycelium compared with
      spores. However, in the analysis of outdoor air, in view of the presence of mould
      mainly in the form of spores and the degradation of ergosterol by UV radiation,
      analysis of that compound may indicate a lower level of contamination compared
      with the culture method.

PMID- 25750477
TI  - Effects of meteorological factors on the composition of selected fungal spores in
      the air.
AB  - The aim of the study was to determine functional relationships between
      composition of air spora and meteorological factors, using multivariate
      statistical technique: canonical correspondence analysis (CCA). Analyses were
      conducted for the data collected during the 4 year (2007-2010) and, in order to
      show the dynamics of such relationships, for each year separately. The CCA
      results indicated that all statistically significant variables accounted for 15.3
      % of the total variance in the spore data in the 4 years. The largest amount of
      the total variance was explained in this period by the mean air temperature (9.2
      %). The meteorological factors impacted spore composition differently in
      different years, when analysis was done for each year separately. The highest
      values of the total variance in the spore data, explained by the statistically
      significant variables, were found in 2010 (32.3 %), with the highest contribution
      of mean air temperature (23.8 %). In that year, the above-mentioned parameter had
      the lowest value in comparison to other years. Canonical correspondence analysis
      provides not only a comprehensive assessment of the impact of meteorological
      factors on specific spore combinations in the air, but also informative graphical
      presentations of the results, illustrating the correlation between the occurrence
      of particular spore taxa and meteorological variables.

PMID- 25750478
TI  - A Preliminary Examination of the Role of Emotion Differentiation in the
      Relationship between Borderline Personality and Urges for Maladaptive Behaviors.
AB  - BACKGROUND AND OBJECTIVES: Impulsive, maladaptive, and potentially self-damaging
      behaviors are a hallmark feature of borderline personality (BP) pathology.
      Difficulties with emotion regulation have been implicated in both BP pathology
      and maladaptive behaviors. One facet of emotion regulation that may be
      particularly important in the relation between BP pathology and urges for
      maladaptive behaviors is emotion differentiation. METHODS: Over one day, 84
      participants high (n = 34) and low (n = 50) in BP pathology responded to
      questions regarding state emotions and urges to engage in maladaptive behaviors
      using handheld computers, in addition to a measure of emotion-related
      difficulties controlling impulsive behaviors. RESULTS: Results revealed that
      individuals high in BP pathology reported greater emotion-related impulsivity as
      well as daily urges to engage in maladaptive behaviors. However, the association
      between BP group and both baseline emotion-related impulsivity and daily urges
      for maladaptive behaviors was strongest among individuals who had low levels of
      positive emotion differentiation. Conversely, negative emotion differentiation
      did not significantly moderate the relationships between BP group and either
      emotion-related difficulties controlling impulsive behaviors or state urges for
      maladaptive behaviors. LIMITATIONS: Limitations to the present study include the
      reliance upon an analogue sample and the relatively brief monitoring period.
      CONCLUSIONS: Despite limitations, these results suggest that, among individuals
      with high BP pathology, the ability to differentiate between positive emotions
      may be a particularly important target in the reduction of maladaptive behaviors.

PMID- 25750479
TI  - The occurrence of female-to-male partner violence among male intimate partner
      violence offenders mandated to treatment: a brief research report.
AB  - Little is known about the perceived perpetration of female-to-male intimate
      partner violence by victims of male offenders mandated to treatment. Sixty-eight
      male perpetrators of partner violence completed measures of dyadic violent and
      aggressive responding at intake and at a 12-week follow-up. Approximately 20% of
      male offenders reported partner violence perpetration and 30% reported
      victimization with bidirectional violence as the most common configuration of
      couple violence. Maladaptive responses to conflict were prevalent across
      partners. Significant and highly correlated reductions in aversive behaviors were
      detected across the assessment period for both males and their female partners.
      Results are interpreted within the context of motivational models of female-to
      male partner violence and current treatment approaches.

PMID- 25750480
TI  - Toward a Framework for Multicultural STEM-Focused Career Interventions.
AB  - Numerous federal and national commissions have called for policies, funds, and
      initiatives aimed at expanding the nation's science, technology, engineering, and
      mathematics (STEM) workforce and education investments to create a significantly
      larger, more diverse talent pool of individuals who pursue technical careers.
      Career development professionals are poised to contribute to the equity discourse
      about broadening STEM participation. However, few are aware of STEM-related
      career development matters, career opportunities and pathways, or strategies for
      promoting STEM pursuits. The author summarizes STEM education and workforce
      trends and articulates an equity imperative for broadening and diversifying STEM
      participation. The author then offers a multicultural STEM-focused career
      development framework to encourage career development professionals' knowledge
      and awareness of STEM education and careers and delineates considerations for
      practice aimed at increasing the attainment and achievement of diverse groups in
      STEM fields.

PMID- 25750481
TI  - Why Do You Make Us Feel Good? Correlates and Interpersonal Consequences of
      Affective Presence in Speed-dating.
AB  - Recent research indicates that people consistently make others feel a certain way
      (e.g. happy or stressed). This individual difference has been termed affective
      presence, but little is known about its correlates or consequences. The present
      study investigated the following: (i) whether affective presence influences
      others' romantic interest in a person and (ii) what types of people have positive
      and negative affective presence. Forty volunteers took part in a speed-dating
      event, during which they dated six or seven opposite-sex partners. A Social
      Relations Model analysis confirmed that individuals prompted consistent positive
      emotional reactions in others. Participants were more likely to want to see dates
      with greater positive affective presence again in the future, and positive
      affective presence explained the effects of perceived responsiveness on romantic
      interest. Associations between positive affective presence and trait predictors,
      including emotion regulation, emotional expressiveness, attachment style,
      agreeableness and extraversion, were also observed. The findings indicate that
      what emotionally distinguishes one individual from another lies in part in the
      emotional consequences of their behaviours on others. (c) 2013 The Authors.
      European Journal of Personality published by John Wiley & Sons Ltd on behalf of
      European Association of Personality Psychology.

PMID- 25750482
TI  - Hydrolytic Fitness of N-glycosyl Bonds: Comparing the Deglycosylation Kinetics of
      Modified, Alternative and Native Nucleosides.
AB  - Nature's selection of the contemporary nucleobases in RNA and DNA continues to
      intrigue the origin of life community. While the prebiotic synthesis of the N
      glycosyl bond has historically been a central area of investigation, variations
      in hydrolytic stabilities among the N-glycosyl bonds may have presented an
      additional selection pressure that contributed to nucleobase and nucleoside
      evolution. To experimentally probe this hypothesis, a systematic kinetic analysis
      of the hydrolytic deglycosylation reactions of modified, alternative and native
      nucleosides was undertaken. Rate constants were measured as a function of
      temperature (at pH 1) to produce Arrhenius and Eyring plots for extrapolation to
      37 degrees C and determination of thermodynamic activation parameters. Rate
      enhancements based on the differences in reaction rates of deoxyribo- and ribo
      glycosidic bonds were found to vary under the same conditions. Rate constants of
      deoxynucleosides were also measured across the pH range of 1 - 3 (at 50 degrees
      C), which highlighted how simple changes to the heterocycle alone can lead to
      significant variation in deglycosylation rates. The contemporary nucleosides
      exhibited the slowest deglycosylation rates in comparison to the non
      native/alternative nucleosides, which we suggest as experimental support for
      nature's selection of the fittest N-glycosyl bonds.

PMID- 25750483
TI  - Osteoarthritis: A Critical Review.
AB  - Patients with osteoarthritis (OA) are faced with a barrage of treatment options,
      from recommendations from friends and social media to medications prescribed by
      the primary care physician. The purpose of this article is to critically review
      current approaches to generalized or monoarticular OA based on available evidence
      and to illustrate multidisciplinary and multimodal treatment strategies for the
      management of OA. Treatment options assessed for efficacy include patient
      education; oral and topical pharmacological agents; complementary and alternative
      medicine; surgery; manual medicine; acupuncture; interventional procedures
      (corticosteroid injection, viscosupplementation, and pulsed radiofrequency);
      bracing; assistive devices; physical therapy; and physical modalities.
      Multidisciplinary and multimodal treatment strategies combined with early
      detection and prevention strategies provide the best benefit to patients. This
      review also illustrates that traditional and alternative modalities of treatment
      can be both synergistic and beneficial. Physicians should be aware of the variety
      of tools available for the management of OA and the associated symptoms. Those
      healthcare providers who can best individualize treatment plans for specific
      patients and inspire their patients to embrace healthy lifestyle modifications
      will achieve the best results.

PMID- 25750484
TI  - A Review of Spasticity Treatments: Pharmacological and Interventional Approaches.
AB  - Spasticity is a velocity-dependent increase in muscle tone and uncontrolled,
      repetitive, involuntary contractions of skeletal muscles. Spasticity presents as
      upper motor neuron symptoms in patients with central nervous system pathology
      such as stroke, spinal cord injury, brain injury, or multiple sclerosis. As a
      result, a patient can have significant pain and limited mobility, which can lead
      to decreased quality of life and difficulty maintaining personal care. In this
      article we discuss mechanisms, indications, efficacy, and side effects of the
      most accepted current treatments. Currently available treatment options include
      oral medications and interventional procedures. Oral medications comprise
      centrally acting agents, such as baclofen, clonidine, and tizanidine, as well as
      anticonvulsants such as benzodiazepines and gabapentin and peripherally acting
      dantrolene. Interventional procedures include focal injections of botulinum
      toxin, phenol or alcohol, and an intrathecal baclofen pump. Surgical treatments
      include selective dorsal rhizotomy and neurectomy. We found that there are
      several treatments available with data to support their use, but many still need
      further research to prove their efficacy and develop optimal utilization.

PMID- 25750486
TI  - Writing Quality in Chinese Children: Speed and Fluency Matter.
AB  - There were two goals of the present study. The first was to create a scoring
      scheme by which 9-year-old Chinese children's writing compositions could be rated
      to form a total score for writing quality. The second was to examine cognitive
      correlates of writing quality at age 9 from measures administered at ages 6-9.
      Age 9 writing compositions were scored using a 7-element rubric; following
      confirmatory factor analyses, 5 of these elements were retained to represent
      overall writing quality for subsequent analyses. Measures of vocabulary
      knowledge, Chinese word dictation, phonological awareness, speed of processing,
      speeded naming, and handwriting fluency at ages 6-9 were all significantly
      associated with the obtained overall writing quality measure even when the
      statistical effect of age was removed. With vocabulary knowledge, dictation
      skill, age, gender, and phonological awareness included in a regression equation,
      35% of the variance in age 9 writing quality was explained. With the variables of
      speed of processing, speeded naming, and handwriting fluency additionally
      included as a block, 12% additional variance in the equation was explained. In
      addition to gender, overall unique correlates of writing quality were dictation,
      speed of processing, and handwriting fluency, underscoring the importance of both
      general automaticity and specific writing fluency for writing quality development
      in children.

PMID- 25750485
TI  - Central Neuropathic Pain in Spinal Cord Injury.
AB  - Spinal cord injury (SCI) is a devastating medical condition affecting 1.2 million
      people in the United States. Central neuropathic pain is one of the most common
      medical complications of SCI. Current treatment options include opioids,
      antiepileptic agents such as gabapentin, antispastic agents such as baclofen or
      tizanidine, and tricyclic acid. Other options include complementary,
      nonpharmacological treatment such as exercise or acupuncture, interventional
      treatments, and psychological approaches. Although these treatment options exist,
      central neuropathic pain in patients with SCI is still extremely difficult to
      treat because of its complexity. To develop and provide more effective treatment
      options to these patients, proper assessment of and classification tools for
      central neuropathic pain, as well as a better understanding of the
      pathophysiology, are needed. A combination of approaches, from standard general
      pain assessments to medically specific questions unique to SCI pathophysiology,
      is essential for this population. A multidisciplinary approach to patient care,
      in addition with a better understanding of pathophysiology and diagnosis, will
      lead to improved management and treatment of patients with SCI displaying central
      neuropathic pain. Here we summarize the most recent classification tools,
      pathophysiology, and current treatment options for patients with SCI with central
      neuropathic pain.

PMID- 25750487
TI  - Romance, recovery & community re-entry for criminal justice involved women:
      Conceptualizing and measuring intimate relationship factors and power.
AB  - Researchers have suggested that interpersonal relationships, particularly
      romantic relationships, may influence women's attempts at substance abuse
      recovery and community re-entry after criminal justice system involvement. The
      present paper evaluates relational and power theories to conceptualize the
      influence of romantic partner and romantic relationship qualities on pathways in
      and out of substance abuse and crime. The paper then combines these
      conceptualizations with a complementary empirical analysis to describe an ongoing
      research project that longitudinally investigates these relational and power
      driven factors on women's substance abuse recovery and community re-entry success
      among former substance abusing, recently criminally involved women. This paper is
      designed to encourage the integration of theory and empirical analysis by
      detailing how each of these concepts are operationalized and measured. Future
      research and clinical implications are also discussed.

PMID- 25750488
TI  - Group descent algorithms for nonconvex penalized linear and logistic regression
      models with grouped predictors.
AB  - Penalized regression is an attractive framework for variable selection problems.
      Often, variables possess a grouping structure, and the relevant selection problem
      is that of selecting groups, not individual variables. The group lasso has been
      proposed as a way of extending the ideas of the lasso to the problem of group
      selection. Nonconvex penalties such as SCAD and MCP have been proposed and shown
      to have several advantages over the lasso; these penalties may also be extended
      to the group selection problem, giving rise to group SCAD and group MCP methods.
      Here, we describe algorithms for fitting these models stably and efficiently. In
      addition, we present simulation results and real data examples comparing and
      contrasting the statistical properties of these methods.

PMID- 25750489
TI  - Simplified Warfarin Dose-response Pharmacodynamic Models.
AB  - Warfarin is a frequently used oral anticoagulant for long-term prevention and
      treatment of thromboembolic events. Due to its narrow therapeutic range and large
      inter-individual dose-response variability, it is highly desirable to personalize
      warfarin dosing. However, the complexity of the conventional kinetic
      pharmacodynamic (K-PD) models hampers the development of the personalized dose
      management. To avert this challenge, we propose simplified PD models for warfarin
      dose-response relationship, which is motivated by ideas from control theory. The
      simplified models were further applied to longitudinal data of 37 patients
      undergoing anticoagulation treatment using the standard two-stage approach and
      then compared with the conventional K-PD models. Data analysis shows that all
      models have a similar predictive ability, but the simplified models are most
      parsimonious.

PMID- 25750490
TI  - New developments in the visual cycle: functional role of 11-cis retinyl esters in
      the retinal pigment epithelium.
AB  - Although both 11-cis and all-tmns retinyl esters exist in the retinal pigment
      epithelium, the relative importance of each in the visual cycle has been unclear.
      Recent data indicate that there are 2 biochemical pathways leading to the
      formation of 11-cis retinoids from the retinal pigment epithelium pool of retinyl
      esters. One well-established pathway is located in the endoplasmic reticulum
      where all-trans retinyl esters are hydrolyzed, isomerized, and then oxidized to
      form 11-cis retinal (endoplasmic reticulum pathway). A more recently identified
      pathway resides within the plasma membrane where 11-cis retinyl esters are
      hydrolyzed directly to 11-cis retinol (plasma membrane pathway). Either or both
      pathways may provide 11-cis retinoids for regeneration of rod and cone visual
      pigments. Recent reports have suggested that the regeneration of rod and cone
      pigments are carried out by different mechanisms, and that 11-cis retinyl esters
      (plasma membrane pathway) in the retinal pigment epithelium may be specific to
      cone pigment regeneration. In this paper we review both visual pathways and
      consider data in support of the hypothesis that 1 of these 2 pathways' (the
      plasma membrane pathway) functions to provide visual pigment chromophores
      selectively for cone photoreceptors.

PMID- 25750491
TI  - Longitudinal Associations Among Religiousness, Delay Discounting, and Substance
      Use Initiation in Early Adolescence.
AB  - Prior research indicates that religiousness is related negatively to adolescent
      health risk behaviors, yet how such protective effects operate is not well
      understood. This study examined the longitudinal associations among
      organizational and personal religiousness, delay discounting, and substance use
      initiation (alcohol, cigarette, and marijuana use). The sample comprised 106
      early adolescents (10-13 years of age, 52% female) who were not using substances
      at Time 1. Path analyses suggested that high levels of personal religiousness at
      Time 1 were related to low levels of substance use at Time 2 (2.4 years later),
      mediated by low levels of delay discounting. Delay discounting appears to be an
      important contributor to the protective effect of religiousness on the
      development of substance use among adolescents.

PMID- 25750492
TI  - Gender, Contraceptive Attitudes, and Condom Use in Adolescent Romantic
      Relationships: A Dyadic Approach.
AB  - Although sexual risk behavior occurs in a dyadic context, most studies of
      adolescent sexual behavior focus on individuals. This study uses couple data (N =
      488 couples) from the National Longitudinal Study of Adolescent Health to examine
      how partners' contraceptive attitudes correlate over time and whether male or
      female partners' attitudes are better predictors of condom use. Net of their own
      prior attitudes, partners' prior attitudes predicted both male and female
      adolescents' Wave 2 attitudes. This association was stronger for female than for
      male adolescents, suggesting that female attitudes were influenced more by males'
      prior attitudes than vice versa. When entered together, only male adolescents'
      attitudes predicted dyadic condom use. Findings suggest that male partners may
      have greater influence on adolescent contraceptive decisions, and that prevention
      programs should emphasize the relational context of sexual behavior.

PMID- 25750493
TI  - What Do Urban Black Mothers Tell Their Adolescents About Alcohol And Other Drugs?
AB  - The current study utilized qualitative content analysis to examine messages
      conveyed about alcohol and other drugs by urban Black mothers (N=130) with a
      personal, familial, or personal and familial history of problematic substance use
      to younger and older adolescents (M = 15.2 years). Data from a two-cohort
      longitudinal sample revealed considerable similarity in themes across the younger
      and older cohorts. Results suggest Black mothers offer more messages of
      information and advice to younger adolescents, while communicating directives
      related to use to older adolescents.

PMID- 25750494
TI  - The BlackBerry Project: The Hidden World of Adolescents' Text Messaging and
      Relations With Internalizing Symptoms.
AB  - In this naturalistic study of adolescents' text messaging, participants (N = 172,
      81 girls, age 14) were given BlackBerry devices configured to save their text
      messages to a secure archive for coding. Two, 2-day transcripts collected four
      months apart within the same academic year were microcoded for content. Results
      showed that most text message utterances were positive or neutral, and that
      adolescents sent text messages primarily to peers and to romantic partners. Only
      a few sex differences emerged. Frequency of text messages containing negative
      talk positively predicted overall internalizing symptoms and anxious depression.
      Text messaging about sex was positively associated with overall internalizing and
      somatic complaints for girls, but not for boys.

PMID- 25750495
TI  - Long-term Effects of Fathers' Depressed Mood on Youth Internalizing Symptoms in
      Early Adulthood.
AB  - While an accumulating body of research has documented increased risk for
      psychopathology among children of depressed fathers, most studies have used cross
      sectional design and little is known about offspring outcomes beyond childhood.
      Using prospective data from a community sample (N = 395), we found that paternal
      depressive symptoms when children were in early adolescence (age 13) predicted
      offspring depressive and anxiety symptoms at age 21, controlling for baseline
      youth symptoms, maternal depressive symptoms, and other known correlates of
      internalizing problems in early adulthood. Associations were not moderated by
      maternal depressive symptoms or child gender. These results suggest that the
      unique and long-term effects of paternal depression on children's risk for mood
      disorders may persist into adulthood.

PMID- 25750496
TI  - Schools, Peers, and Prejudice in Adolescence.
AB  - Adolescents' perceptions of the prejudice in their social environments can factor
      into their developmental outcomes. The degree to which others in the environment
      perceive such prejudice-regardless of adolescents' own perceptions-also matters
      by shedding light on the contextual climate in which adolescents spend their
      daily lives. Drawing on the National Longitudinal Study of Adolescent Health,
      this study revealed that schoolwide perceptions of peer prejudice, which tap into
      the interpersonal climate of schools, appeared to be particularly risky for
      adolescents' academic achievement. In contrast, adolescents' own perceptions of
      peer prejudice at schools were associated with their feelings of alienation in
      school. Importantly, these patterns did not vary substantially by several markers
      of vulnerability to social stigmatization.

PMID- 25750497
TI  - Risks and benefits of text message-delivered and small group-delivered sexual
      health interventions among African American women in the Midwestern U.S.
AB  - Interventions to decrease acquisition and transmission of sexually transmitted
      diseases among African American women using text messages versus small group
      delivery modalities pose distinct research risks and benefits. Determining the
      relative risk-benefit ratio of studies using these different modalities has
      relied on the expertise of investigators and their institutional review boards.
      In this study, African American women participated in focus groups and surveys to
      elicit and compare risks and benefits inherent in these two intervention delivery
      modalities, focusing on issues such as convenience, privacy, and stigma of
      participation. Some risk/benefit variables were implicated in willingness to
      participate the two intervention modalities.

PMID- 25750498
TI  - Consent Challenges for Participation of Young Men Who Have Sex With Men (YMSM) in
      HIV Prevention Research in Thailand.
AB  - Young men who have sex with men (YMSM) under 18 years are often excluded from HIV
      prevention research in Thailand due to cultural attitudes toward youth sexuality,
      social stigma, and difficulties obtaining guardian permission. Culturally
      sensitive focus group discussions conducted with parents and YMSM in Bangkok,
      Thailand identified barriers and facilitators related to minors' participation in
      HIV prevention research. Although gender and class differences emerged, mothers
      and fathers were generally accepting of research to reduce HIV risk, but not in
      favor of waiver. Youth's positive attitude toward parental permission was
      tempered by concerns about harms posed by disclosing same-sex attraction through
      permission forms.

PMID- 25750499
TI  - Synthesis and selected immunological properties of 10-substituted 1,8
      diazaphenothiazines.
AB  - A new type of tricyclic azaphenothiazines-1,8-diazaphenothiazines-was obtained in
      the reaction of 2,3- and 3,4-disubstituted pyridines. The reaction ran as the
      Smiles rearrangement. The 1,8-diazaphenothiazine system was determined using NOE
      experiment and 2D NMR spectra (COSY, HSQC, HMBC). 10H-1,8-diazaphenothiazine was
      transformed into 10-derivatives with alkyl, aminoalkyl, amidoalkyl,
      sulfonamidoalkyl, and nitrogen half-mustard groups. The compounds were tested for
      their effects on phytohemagglutinin A-induced proliferative response of human
      peripheral blood mononuclear cells (PBMC) and lipopolysaccharide-induced tumor
      necrosis factor alpha production by human whole blood cultures. The compounds
      exhibited differential, dose-dependent inhibitory activities in these tests. All
      the compounds were low toxic against PBMC. The compounds showing the highest
      antiproliferative activity strongly inhibited the growth of leukemia L-1210 and
      colon cancer SW-948 cell lines, similarly as cisplatin, a reference drug.

PMID- 25750500
TI  - Synthesis and Evaluation of Mefway Analogs as Ligands for Serotonin 5HT1A
      Receptors.
AB  - 18F-Mefway (N-{2-[4-(2'-methoxyphenyl)piperazinyl]ethyl}-N-(2-pyridyl)-N-(4'-18F
      fluoro-methylcyclohexane)carboxamide) was developed and evaluated for use as a
      PET ligand for imaging 5-HT1A receptors. Ongoing studies of 18F-Mefway have shown
      it to be an effective PET radiotracer. We have synthesized isomers of Mefway by
      changing the position of the methyl-group in attempts to evaluate stability for
      imaging purposes. 2-Methyl-, 3-methyl-, and 4-methyl-cyclohexane-1-carboxylic
      acids and 3-carbomethoxy-, 4-carbomethoxycyclohexane-1-carboxylic acids were
      coupled with WAY-100634 to provide the methylcyclohexyl derivatives (2-, 3- and 4
      methyl). Mefway and 3-Mefway analogs were prepared by reduction of carbomethoxy
      derivatives followed by fluorination. In vitro binding affinities for the
      methylated derivatives in rat brain homogenates was found to be 10.4 nM (2
      methyl), 77 nM (3-methyl) and 21.5 nM (4-methyl). Binding affinity of 3-Mefway
      and 4-Mefway was found to be 17.4 nM and 6.26 nM, respectively. Our results
      suggest that 3-methyl/3-fluoromethyl substituent has approx. 3-fold lower
      affinities compared to the 4-methyl/4-fluoromethyl substituent.

PMID- 25750501
TI  - Synthesis of quinoline/naphthalene-containing azaphenothiazines and their potent
      in vitro antioxidant properties.
AB  - New tetracyclic and pentacyclic azaphenothiazines containing one or two quinoline
      rings instead of benzene rings were obtained in the original reactions of
      isomeric diquinodithiins, dichlorodiquinolinyl sulfides, and disulfide with
      aromatic amines. The type of ring fusion in the azaphenothiazine system was
      concluded from the 1H NMR spectra. The obtained azaphenothiazines were evaluated
      in vitro for their antioxidant activity on rat hepatic microsomal membranes for
      protection of non-enzymatic lipid peroxidation promoted by the Fe2+/ascorbic acid
      redox system. Most compounds exhibited a very significant antioxidant activity
      with IC50 values between 1 and 23 MUM. The degree of antioxidant activity depends
      on the lipophilicity and molecular size as well as the (non)substitution of the
      thiazine nitrogen atom and type of ring system fusion. It is the first time to
      our knowledge that azaphenothiazines are shown to exhibit such potent antioxidant
      activity.

PMID- 25750502
TI  - Economic Hardship, Parent Positive Communication and Mental Health in Urban
      Adolescents Seeking Outpatient Psychiatric Care.
AB  - Economic hardship and poor parenting behaviors are associated with increased risk
      for mental health problems in community adolescents. However, less is known about
      the impact of socioeconomic status (SES) and parenting behaviors on youth at
      elevated risk for mental health problems, such as teens seeking outpatient
      psychiatric care. This study examined whether family SES and parent positive
      communication were directly and indirectly associated with mental health symptoms
      six months later in urban teens seeking outpatient treatment, after accounting
      for baseline levels of symptoms. At baseline, adolescent participants (N = 346;
      42% female; 61% African-American) ages 12 to 19 years old (M = 14.9; SD = 1.8)
      and their primary caregivers reported on SES and teen internalizing and
      externalizing symptoms and engaged in a videotaped discussion of a real-life
      conflict to assess parent positive communication. At 6-month follow-up, 81% (N =
      279) of families were retained and teens and caregivers again reported
      internalizing and externalizing symptoms. Structural Equation Modeling (SEM) was
      used to test the hypothesized models with a sample of 338, using the full
      information likelihood method to adjust for missing data. For parent-reported
      externalizing symptoms, SEM revealed support for the indirect association of SES
      with follow-up externalizing symptoms via parent positive communication and
      externalizing symptoms at baseline. For parent reported internalizing symptoms,
      there was a direct association between SES and follow-up internalizing symptoms,
      but not an indirect effect via parent positive communication. Youth-reported
      symptoms were not associated with SES nor with parent positive communication.
      Current findings extend prior research on adolescent mental health in a diverse
      sample of urban youth seeking outpatient psychiatric care. These families may
      benefit from interventions that directly target SES-related difficulties and
      parent positive communication.

PMID- 25750503
TI  - Maternal mental health and children's internalizing and externalizing behaviors:
      Beyond maternal substance use disorders.
AB  - Maternal substance abuse and mental disorders can have adverse impacts on child
      development. We investigated the impact of maternal mental health on child
      behaviors based on a long-term follow-up study of mothers and their children
      approximately 10 years after mothers' admission to drug abuse treatment. Mothers
      (n=396) were assessed at admission to drug treatment during 2000 to 2002, and at
      follow-up in 2010-2011. At follow-up, each mother was asked to assess one target
      child using the Child Behavior Checklist for ages 6-18 (CBCL). Mothers' mental
      disorder diagnoses were obtained from records maintained by the California
      Department of Mental Health in 2009. About 46% of mothers had comorbid mental
      disorders; 27% had depressive disorder, 15% bipolar disorder, 15% adjustment
      disorder, 13% anxiety disorder, and 6% psychotic disorder. Of these mothers, more
      than half had two or more mental disorder diagnoses. The average age of the
      target child was approximately 10 years old (range 6 to 17). Relative to children
      of mothers without comorbid mental disorders, children were more likely to
      demonstrate internalizing behaviors if their mothers had comorbid
      depression/anxiety disorders (OR=2.0, 95%CI:1.0-4.0) or severe mental disorders
      (psychoses, bipolar) (OR=3.4, 95%CI:1.5-7.6). For externalizing behaviors, family
      problems was the only significant predictor (OR=3.2, 95%CI:1.7-6.0 for children
      of mothers with depression/anxiety disorders, OR=3.9, 95%CI:1.9-7.8 for severe
      mental disorders). Addressing maternal mental disorders (particularly severe
      mental disorders) and family problems are important for child well-being as these
      factors were significantly related to emotional and problem behaviors of
      children.

PMID- 25750504
TI  - Associations Among Parental Stress, Child Competence, and School-Readiness:
      Findings from the PACE Study.
AB  - Perceived parental stress has been consistently shown to negatively impact child
      functioning and ability to cope with stressful situations. Utilizing data from
      the parenting our children to excellence program, the current study examined the
      relationships among perceived parenting stress, coping competence, and school
      readiness in a sample of African American and Caucasian parents of preschool
      children (age 3-6) considered at high risk for child physical abuse. We
      hypothesized that child competence would mediate the relation between perceived
      parental stress and children's school readiness. We tested a longitudinal latent
      variable model and found that parent-reported (but not teacher-reported) child
      competence mediated the relation between perceived parental stress and school
      readiness, controlling for family income, parent's education level, and child's
      sex. These results suggest that parents' perceived stress plays a role in both
      how they view their children's competence and how children perform academically.

PMID- 25750505
TI  - Link between Monitoring Behavior and Adolescent Adjustment: An Analysis of Direct
      and Indirect Effects.
AB  - The purpose of the current investigation was to explore whether monitoring
      behavior (i.e., parental solicitation, child disclosure, and parental
      involvement) was directly and indirectly (via parental knowledge and parent-youth
      openness) related to adolescent adjustment (i.e., antisocial behavior, substance
      use, and school grades). The sample consisted of 206 families with adolescents
      (ages 10-18 years) from predominantly low-income, high-risk neighborhoods.
      Monitoring behavior (parent reports), parental knowledge and parent-youth
      openness (youth reports), and adolescent adjustment (parent and youth reports)
      were all based on questionnaire data collected during a laboratory assessment.
      Results showed that when the monitoring behavior factors were examined
      simultaneously, only child disclosure was significantly and inversely related to
      youth antisocial behavior. In contrast, only parental involvement was
      significantly associated with less substance use. Moreover, school grades were
      significantly and incrementally predicted by both child disclosure and parental
      involvement. Parental solicitation was not significantly related to any of the
      adolescent outcomes. The findings also demonstrated evidence of indirect effects
      (via parental knowledge) in the link between monitoring behavior and adolescent
      adjustment. Implications regarding the socialization process during adolescence
      are discussed.

PMID- 25750506
TI  - Predictors, Moderators, and Treatment Parameters of Community and Clinic-Based
      Treatment for Child Disruptive Behavior Disorders.
AB  - This study examines predictors, moderators, and treatment parameters associated
      with two key child outcomes in a recent clinical trial comparing the effects of a
      modular treatment that was applied by study clinicians in the community (COMM) or
      a clinic (CLINIC) for children with oppositional defiant disorder (ODD) or
      conduct disorder (CD). Based on a literature review, moderator and predictor
      variables across child, parent, and family domains were examined in relation to
      changes in parental ratings of the severity of externalizing behavior problems or
      the number of ODD and CD symptoms endorsed on psychiatric interview at
      pretreatment, posttreatment, and 36-month posttreatment follow-up. In addition,
      associations between parameters of treatment (e.g., hours of child, parent, and
      parent-child treatment received, treatment completion, referral for additional
      services at discharge) and child outcomes were explored. Path models identified
      few moderators (e.g., level of child impairment, attention deficit hyperactivity
      disorder diagnosis, level of family conflict) and several predictors (child
      trauma history, family income, parental employment, parental depression) of
      treatment response. Treatment response was also related to a few treatment
      parameters (e.g., hours of child and parent treatment received, treatment
      completion, referral for additional services at discharge). We discuss the
      implications of these findings for maximizing the benefits of modular treatment
      by optimizing or personalizing intervention approaches for children with behavior
      disorders.

PMID- 25750507
TI  - Distress in the Desert: Neighborhood Disorder, Resident Satisfaction, and Quality
      of Life during the Las Vegas Foreclosure Crisis.
AB  - Using surveys collected from a sample of households nested within 'naturally
      occurring' neighborhoods in Las Vegas, NV during the 2007-2009 economic
      recession, this study examines the associations between real and perceived
      measures of neighborhood distress (foreclosure rate, physical decay, crime) and
      residents' reports of neighborhood quality of life and neighborhood satisfaction.
      Consistent with social disorganization theory, both real and perceived measures
      of neighborhood disorder were negatively associated with quality of life and
      neighborhood satisfaction. Residents' perceptions of neighborliness partially
      acted as a buffer against the effects of neighborhood distress, including housing
      foreclosures, on quality of life and neighborhood satisfaction.

PMID- 25750509
TI  - Fall Prevention for Community-Living Older Adults: A Tale of Two Systematic
      Reviews.

PMID- 25750508
TI  - Preventing COPD exacerbations: new options for a crucial and growing problem.

PMID- 25750510
TI  - CYP1B1 copy number variation is not a major contributor to primary congenital
      glaucoma.
AB  - PURPOSE: To evaluate the prevalence and the diagnostic utility of testing for
      CYP1B1 copy number variation (CNV) in primary congenital glaucoma (PCG) cases
      unexplained by CYP1B1 point mutations in The Australian and New Zealand Registry
      of Advanced Glaucoma. METHODS: In total, 50 PCG cases either heterozygous for
      disease-causing variants or with no CYP1B1 sequence variants were included in the
      study. CYP1B1 CNV was analyzed by Multiplex Ligation-dependent Probe
      Amplification (MLPA). RESULTS: No deletions or duplications were found in any of
      the cases. CONCLUSION: This is the first study to report on CYP1B1 CNV in PCG
      cases. Our findings show that this mechanism is not a major contributor to the
      phenotype and is of limited diagnostic utility.

PMID- 25750511
TI  - Associations of polymorphisms of LOXL1 gene with primary open-angle glaucoma: a
      meta-analysis based on 5,293 subjects.
AB  - OBJECTIVE: Previous studies indicated that the relationship between lysyl oxidase
      like 1 (LOXL1) gene polymorphisms and primary open-angle glaucoma (POAG) remains
      inconsistent. In the present study, we aimed to perform a meta-analysis to
      investigate the association of LOXL1 polymorphisms with POAG risk. METHODS:
      Literatures were electronically searched in the PubMed, EMBASE, CNKI, Wanfang,
      and VIP databases. The published literatures, which are case-control or cohort
      studies on the relationship between the polymorphisms (rs1048661, rs3825942,
      rs2165241) of the LOXL1 gene and POAG, were documented. RESULTS: We included 13
      literatures including 5,293 subjects for the present study. A meta-analysis
      showed that the risk of POAG in individuals carrying the C allele of rs2165241
      was 1.26 times higher compared with those carrying the T allele (odds ratio
      (OR)=1.26, 95% confidence interval (CI): 1.09~1.46) in the total population. In
      the Caucasian population, we also found that individuals carrying the C allele of
      rs2165241 have an increased risk for POAG compared to those subjects carrying the
      T allele (OR=1.42, 95% CI: 1.19~1.69, p=0.0001). In addition, we found that the
      rs1048661 polymorphism was associated with POAG in the Asian population (OR=1.17,
      95% CI: 1.02~1.35, p=0.03), and rs3825942 was associated with POAG in the
      Caucasian population (OR=2.69, 95% CI: 1.61~4.47, p<0.001). CONCLUSIONS: The
      polymorphisms of the LOXL1 gene were associated with the susceptibility of POAG.

PMID- 25750512
TI  - Intimate Partner Violence and Drinking Among Victims of Adult Sexual Assault.
AB  - Intimate partner violence is associated with problem drinking. Correlates of
      alcohol consumption frequency and problem drinking were examined among female
      sexual assault survivors (N = 1863). Data were analyzed with blockwise multiple
      regressions. Results show heavy alcohol consumption and problem drinking were
      associated with intimate partner violence history, sexual assault by
      strangers/acquaintances, and maladaptive coping. Physical Intimate Partner
      Violence (IPV) history and partner sexual assault showed distinct effects on
      drinking outcomes among women. Physical IPV history partially mediated the effect
      of Child Sexual Abuse (CSA) on problem drinking. Research is needed to examine
      the relationship between victimization histories and drinking among female sexual
      assault victims. This may enable treatments and interventions to be tailored to
      the trauma histories of female victims.

PMID- 25750513
TI  - Do physicians communicate the adverse effects of medications that older patients
      want to hear?
AB  - BACKGROUND AND OBJECTIVES: Physicians routinely discuss adverse effects of
      medications, but whether discussions match older patients' desire for information
      is unexplored. This study compares patient preferences for adverse effect
      discussions with reported physician practice. METHODS: Cross-sectional survey of
      a convenience sample of 100 practicing primary care physicians from 9 medical
      groups and 178 patients recruited from 11 senior centers in the Los Angeles
      metropolitan area. Physicians listed the adverse effects they typically discuss
      when prescribing an ACE inhibitor. Patients were given a hypothetical scenario
      about a new medication prescription, and were asked to circle the three adverse
      effects they most wanted to hear about from a list. RESULTS: More than 90 % of
      patients wanted a physician to discuss medication adverse effects: they wanted
      information about both dangerous (75 % of patients) and common (66 % of patients)
      adverse effects. However, patients most commonly chose to hear about adverse
      effects occurring for < 1 % of patients and selected a wide range of adverse
      effects for discussion. Physicians reported most frequently educating patients
      about more common and life-threatening adverse effects. Patients who wanted to
      discuss more adverse effects were more worried about adverse effects than those
      wishing to hear fewer (4.0 vs. 3.4 on a 5-point Likert scale; p = 0.02).
      CONCLUSIONS: For the studied medication, there was little concordance between the
      medication adverse effects physicians say they discuss and what patients want to
      hear. Physicians cannot practically verbally satisfy patients' information
      desires about the adverse effects of new medications during time-compressed
      office visits. Innovative solutions are needed.

PMID- 25750514
TI  - Evaluation of the efficacy and safety of a new device for eye drops instillation
      in patients with glaucoma.
AB  - OBJECTIVE: This study evaluated the efficacy and safety of a new device
      (Eyedrop((r))) designed for eye drop instillation in patients with and without
      glaucoma. METHODS: This prospective study included consecutive patients with
      glaucoma and healthy participants. After a complete eye examination and
      determination of baseline intraocular pressure (IOP), topical hypotensive
      medication was introduced in both eyes, and the Eyedrop((r)) delivery device (a
      plastic device in which the bottle with eye drops is inserted) was made available
      to all participants (with video and written instructions) for use in one eye,
      randomly chosen. In the second phase, all patients were evaluated by an
      experienced examiner for IOP determination, investigation of possible associated
      side effects, and ease of instilling eye drops (by a visual analog scale [VAS]; 0
      10). RESULTS: Thirty two participants (mean age 42.3+/-16.2 years) were
      evaluated. Of these, 44% had glaucoma. There was no significant difference in
      mean IOP variation when comparing the eye using (-3.9+/-2.9 mmHg) or not using
      the device (-3.3+/-2.6 mmHg; P=0.36). The subjective rating of the facility of
      drops instillation was significantly higher with the Eyedrop((r)) applicator (VAS
      =7.6+/-1.6) than without it (VAS =6.2+/-1.8; P<0.01), with a higher frequency of
      positive device-related evaluations (VAS score >5) among participants without
      prior experience with eye drop instillation (78.6% [11/14]) versus those already
      experienced (66.7% [12/18]). No difference in the frequency of side effects or in
      the distribution pattern of fluorescein between eyes was observed (P>=0.63).
      CONCLUSION: Eyedrop((r)) received a better subjective response regarding the ease
      of instillation of hypotensive eye drops compared to traditional instillation,
      especially in patients with no previous experience with eye drops. Using the
      device did not result in any loss of hypotensive effect or increase in the
      frequency of side effects.

PMID- 25750515
TI  - Causes of isolated recurrent ipsilateral sixth nerve palsies in older adults: a
      case series and review of the literature.
AB  - PURPOSE: The etiology of recurrent isolated sixth nerve palsies in older adults
      has not been well described in the literature. Sixth nerve palsies presenting
      with a chronic, relapsing, and remitting course are uncommon, but can herald a
      diagnosis of high morbidity and mortality in the older population. PATIENTS AND
      METHODS: Our method was a retrospective case series study. A review of clinical
      records of 782 patients >=50 years of age diagnosed with recurrent sixth nerve
      palsies was performed over a 10-year period from 1995-2005 in a neuro
      ophthalmology clinic in Reno, Nevada. A review of the current literature
      regarding similar cases was also performed on PubMed. RESULTS: Seven patients
      >=50 years of age with chronic, recurrent sixth nerve palsies were identified.
      Five were males and two were females. Four of seven (57%) patients had structural
      lesions located in the parasellar or petrous apex cavernous sinus regions. One of
      seven (14.29%) had a recurrent painful ophthalmoplegic neuropathy (International
      Headache Society [IHS] 13.9), previously termed ophthalmoplegic migraine; one of
      seven (14.29%) presented with an intracavernous carotid artery aneurysm; and one
      of seven (14.29%) presented with microvascular disease. CONCLUSION: The clinical
      presentation of an isolated recurrent diplopia from a sixth nerve palsy should
      prompt the neurologist or ophthalmologist to order a magnetic resonance imaging
      (MRI) scan of the brain with and without gadolinium as part of the initial workup
      to rule out a non-microvascular cause, such as a compressive lesion, which can
      increase morbidity and mortality in adults >50 years of age.

PMID- 25750516
TI  - Refractive outcomes of an advanced aspherically optimized profile for myopia
      corrections by LASIK: a retrospective comparison with the standard aspherically
      optimized profile.
AB  - PURPOSE: A retrospective comparison of refractive outcomes of a new, aspherically
      optimized profile with an enhanced energy correction feature (Triple-A) and the
      conventionally used aspherically optimized profile (ASA, or aberration smart
      ablation) for correction of low-to-high myopia. SETTING: Augen-OP-Centrum,
      Cologne, Germany. DESIGN: Retrospective nonrandomized comparative study. METHODS:
      A central database at the Augen-OP-Centrum was used to gather retrospective data
      for low-to-high myopia (up to -10 D). One hundred and seven eyes (56 patients)
      were treated with the ASA profile, and 79 eyes (46 patients) were treated with
      the Triple-A profile. Postoperative outcomes were evaluated at 1 month, 3 months,
      6 months, and 1 year follow-up time points. RESULTS: The Triple-A profile showed
      better predictability indicated by a significantly lower standard deviation of
      residuals (0.32-0.34 vs 0.36-0.44, Triple-A vs ASA) in the 6-month to 1-year
      period. The Triple-A group had better stability across all time intervals and
      achieved better postoperative astigmatism improvements with significantly lower
      scatter. This group achieved better safety at 1 year, with 100% of eyes showing
      no change or gain in Snellen lines, compared with 97% in the ASA group. A better
      safety index was observed for the Triple-A group at later time points. The Triple
      A group had a better efficacy index and a higher percentage of eyes with an
      uncorrected Snellen visual acuity of 20/20 or greater at all investigated follow
      up time points. CONCLUSION: The new aspherically optimized Triple-A profile can
      safely and effectively correct low-to-high myopia. It has demonstrated
      superiority over the ASA profile in most refractive outcomes.

PMID- 25750517
TI  - Ocular manifestations of rheumatoid arthritis and their correlation with anti
      cyclic citrullinated peptide antibodies.
AB  - PURPOSE: To study the ocular manifestations of rheumatoid arthritis and to
      correlate the role of anti-cyclic citrullinated peptide antibody (anti-CCP
      antibody) with the ocular manifestations. METHODS: Three-hundred and ninety-two
      eyes of the 196 rheumatoid arthritis patients who attended the ophthalmology
      outpatient department underwent a detailed ocular examination using slit lamp
      biomicroscopy and ophthalmoscopy. The tear function of all the patients was
      assessed using Schirmer's test, tear film break-up time and ocular surface
      staining. The anti-CCP antibody titers for all the rheumatoid arthritis patients
      were estimated using enzyme-linked immunosorbent assay tests. RESULTS: Seventy
      seven patients (135 eyes, 39%) out of the 196 patients studied had ocular
      manifestations typical of rheumatoid arthritis. Dry eye was the most common
      manifestation (28%, 54 patients). Of the patients, 78% was females (60 patients).
      The mean duration of rheumatoid arthritis in patients with ocular manifestations
      was 5.4+/-2.7 years and without ocular manifestations was 2.1+/-1.6years. Three
      percent of the patients had episcleritis (six patients). Scleritis was present in
      2% of the patients (four patients). Peripheral ulcerative keratitis and
      sclerosing keratitis was present in 1% of the population each (two patients
      each). Eighty-five percent (66 patients) had bilateral manifestations 15% (eleven
      patients) had unilateral manifestations. There was a strong association between
      the presence of anti-CCP antibodies and ocular manifestations of rheumatoid
      arthritis which was shown by the statistically significant P-value of <0.0001.
      CONCLUSION: Ocular manifestations are a significant part of the extra-articular
      manifestation of rheumatoid arthritis. Dry eye was the most common ocular
      manifestation. There was a statistically significant association between the
      presence of anti-CCP antibodies specific to rheumatoid arthritis and the ocular
      manifestations.

PMID- 25750518
TI  - Varicella zoster virus-associated anterior uveitis in a seronegative adult
      without a history of chickenpox.
AB  - AIM: The aim of this report was to present a case of varicella zoster virus (VZV)
      associated anterior uveitis, which developed in an adult who was seronegative for
      anti-VZV antibodies. CASE PRESENTATION: A 66-year-old male patient was referred
      to the National Defense Medical College, Tokorozawa City, Japan with
      iridocyclitis in his right eye. On examination, intraocular pressure was 30 mmHg
      in the right eye, and biomicroscopy revealed ciliary injection, corneal
      epithelial edema, mutton fat keratic precipitates, flare, and infiltrating cells
      in the anterior chamber. Serological tests were negative for anti-VZV antibodies,
      but VZV-DNA copies of 1.28*10(7) copies/mL were detected by quantitative reverse
      transcriptase polymerase chain reaction using the aqueous humor obtained from the
      right eye. Iridocyclitis was reduced by administration of oral valaciclovir in
      addition to corticosteroid eye drops, and serum anti-VZV antibodies were first
      detected after 4 months' administration. When ocular inflammation was resolved
      after 6 months, VZV-DNA could not be detected in the aqueous humor any more.
      CONCLUSION: VZV-associated uveitis may develop in an adult with undetectable
      serum anti-VZV antibodies. Multiplex polymerase chain reaction of the aqueous
      humor is the key investigation necessary for the diagnosis in such cases.

PMID- 25750519
TI  - Fluorescence detection of tramadol in healthy Chinese volunteers by high
      performance liquid chromatography and bioequivalence assessment.
AB  - This study developed a revised high-performance liquid chromatography
      fluorescence method to determine plasma tramadol concentration, and thereby to
      examine the bioequivalence of two tramadol formulations among healthy male
      Chinese volunteers. The study used a double-blind, randomized, 2*2 crossover
      design principle. Calculated pharmacokinetic parameters for both formulations
      were consistent with previous reports. According to the observation of vital
      signs and laboratory measurement, no subjects had any adverse reactions. The
      geometric mean ratios (90% confidence interval) of the test drug/reference drug
      for tramadol were 100.2% (95.3%-103.4%) for the area under the plasma
      concentration-time curve (AUC) from time zero to the last measurable
      concentration, 99.6% (94.2%-102.7%) for the AUC from administration to infinite
      time, and 100.8% (93.1%-106.4%) for maximum concentration. For the 90% confidence
      intervals of the test/reference AUC ratio and maximum concentration ratio of
      tramadol, both were in the acceptance range for bioequivalence. According to the
      two preparations by pharmacokinetic parameter statistics, the half-life, mean
      residence time, and clearance values showed no significant statistical
      differences. Therefore, the conclusion of this study was that the two tramadol
      formulations (tablets and capsules) were bioequivalent. 

PMID- 25750520
TI  - Pharmacokinetic-pharmacodynamic analysis to evaluate the effect of moxifloxacin
      on QT interval prolongation in healthy Korean male subjects.
AB  - A single 400 mg dose of moxifloxacin has been the standard positive control for
      thorough QT (TQT) studies. However, it is not clearly known whether a 400 mg dose
      is also applicable to TQT studies in Asian subjects, including Koreans. Thus, we
      aimed to develop a pharmacokinetic (PK)-pharmacodynamic (PD) model for
      moxifloxacin, to evaluate the time course of its effect on QT intervals in
      Koreans. Data from three TQT studies of 33 healthy male Korean subjects who
      received 400 and 800 mg of moxifloxacin and placebo (water) were used. Twelve
      lead electrocardiograms were taken for 2 consecutive days: 1 day to record
      diurnal changes and the next day to record moxifloxacin or placebo effects.
      Peripheral blood samples were also obtained for PK analysis. The PK-PD data
      obtained were analyzed using a nonlinear mixed-effects method (NONMEM ver. 7.2).
      A two-compartment linear model with first-order absorption provided the best
      description of moxifloxacin PK. Individualized QT interval correction, by heart
      rate, was performed by a power model, and the circadian variation of QT intervals
      was described by two mixed-effect cosine functions. The effect of moxifloxacin on
      QT interval prolongation was well explained by the nonlinear dose-response (Emax)
      model, and the effect by 800 mg was only slightly greater than that of 400 mg.
      Although Koreans appeared to be more sensitive to moxifloxacin-induced QT
      prolongation than were Caucasians, the PK-PD model developed suggests that a 400
      mg dose of moxifloxacin is also applicable to QT studies in Korean subjects. 

PMID- 25750522
TI  - Patients' Experiences of LIving with CANcer-associated thrombosis: the PELICAN
      study.
AB  - INTRODUCTION: Thrombosis remains the most common preventable cause of mortality
      in cancer patients receiving chemotherapy. Whilst the prophylaxis and treatment
      of this condition is well understood, the patient experience and subsequent
      behavioral factors are not. METHODS: Patients receiving treatment for cancer
      associated thrombosis (CAT) were interviewed about their experiences of CAT
      within the context of their cancer journey. Twenty interviews were transcribed
      and analyzed using framework analysis. RESULTS: Chemotherapy patients were well
      informed about the risks of febrile neutropenia, how to recognize it, and when to
      seek medical attention. However, they had limited knowledge about CAT and
      received no information about the condition. Red flag symptoms suggestive of CAT
      were attributed to chemotherapy or the underlying cancer, resulting in delayed
      presentation to hospital, and diagnosis. The CAT journey was considered a
      distressing one, with limited support or information, in complete juxtaposition
      with the treatment they received for their cancer. Patients felt there was little
      ownership for the management of CAT, which further added to their distress.
      CONCLUSION: CAT is a common occurrence and patients view their experiences of it
      within the context of their overall cancer journey. However, patients receive
      little information to help recognize CAT and access timely treatment on the
      development of symptoms. Whilst other cancer complications have clear treatment
      pathways, thrombosis does not appear to have been afforded the same priority. A
      proactive approach to increase patient awareness, coupled with established CAT
      pathways is likely to reduce mortality, morbidity, and long-term psychological
      distress.

PMID- 25750521
TI  - Noncoding RNAs as potential biomarkers to predict the outcome in pancreatic
      cancer.
AB  - Pancreatic ductal adenocarcinoma (PDAC), a common digestive system cancer, is
      highly malignant and has a poor disease outcome. Currently, all available
      examination and detection methods cannot accurately predict the clinical outcome.
      Therefore, it is extremely important to identify novel molecular biomarkers for
      personalized medication and to significantly improve the overall outcome. The
      "noncoding RNAs" (ncRNAs) are a group of RNAs that do not code for proteins, and
      they are categorized as structural RNAs and regulatory RNAs. It has been shown
      that microRNAs and long ncRNAs function as regulatory RNAs to affect the
      progression of various diseases. Many studies have confirmed a role for ncRNAs in
      the progression of PDAC during the last few years. Because of the significant
      role of ncRNAs in PDAC, ncRNA profiling may be used to predict PDAC outcome with
      high accuracy. This review comprehensively analyzes the value of ncRNAs as
      potential biomarkers to predict the outcome in PDAC and the possible mechanisms
      thereof. 

PMID- 25750523
TI  - Dietary education must fit into everyday life: a qualitative study of people with
      a Pakistani background and type 2 diabetes.
AB  - BACKGROUND: The high prevalence of diabetes among South Asian populations in
      European countries partially derives from unhealthy changes in dietary patterns.
      Limited studies address perspectives of South Asian populations with respect to
      utility of diabetes education in everyday life. This study explores perspectives
      on dietary diabetes education and healthy food choices of people living in
      Denmark who have a Pakistani background and type 2 diabetes. METHODS: In-depth
      interviews were conducted between October 2012 and December 2013 with 12
      participants with type 2 diabetes who had received dietary diabetes education.
      Data analysis was systematic and was based on grounded theory principles.
      RESULTS: Participants described the process of integrating and utilizing dietary
      education in everyday life as challenging. Perceived barriers of the integration
      and utilization included a lack of a connection between the content of the
      education and life conditions, a lack of support from their social networks for
      dietary change, difficulty integrating the education into everyday life, and
      failure to include the participants' taste preferences in the educational
      setting. CONCLUSION: Dietary education that is sensitive to the attitudes,
      wishes, and preferences of the participants and that aims at establishing a
      connection to the everyday life of the participants might facilitate successful
      changes in dietary practices among people with a Pakistani background and type 2
      diabetes. The findings suggest that more focus should be placed on collaborative
      processes in the dietary educational setting in order to achieve appropriate
      education and to improve communication between this population and health care
      professionals.

PMID- 25750524
TI  - Functional capacity, physical activity, and quality of life in hypoxemic patients
      with chronic obstructive pulmonary disease.
AB  - BACKGROUND: The risk of hypoxemia increases with the progression of chronic
      obstructive pulmonary disease (COPD) and the deterioration of pulmonary function.
      The aim of this study was to compare functional capacity, physical activity, and
      quality of life in hypoxemic and non-hypoxemic patients with COPD. METHODS:
      Thirty-nine COPD patients (mean age: 62.0+/-7.03 years) were included in this
      study. Arterial blood gas tensions were measured, and patients were divided into
      two groups according to oxygen partial pressure (PaO2), the hypoxemic COPD (PaO2
      <60 mmHg) (n=18), and the control (PaO2 >=60 mmHg) (n=21) groups. Functional
      exercise capacity was evaluated using the 6-minute walk test (6MWT). Oxygen
      saturation, dyspnea, and fatigue perception were measured before and after the
      6MWT. Physical activity was assessed using the International Physical Activity
      Questionnaire (IPAQ) and an accelerometer. Quality of life was assessed using the
      St George's Respiratory Questionnaire (SGRQ). RESULTS: The number of emergency
      visits and hospitalizations were higher in hypoxemic patients (P<0.05). Lung
      function parameters, 6MWT distance, exercise oxygen saturation, IPAQ total score,
      and energy expenditure during daily life were significantly lower, but percentage
      of maximum heart rate reached during the 6MWT was significantly higher, in
      hypoxemic COPD patients than in controls (P<0.05). CONCLUSION: Hypoxemia has a
      profound effect on functional capacity and physical activity in patients with
      COPD.

PMID- 25750525
TI  - The effect of comorbidities on COPD assessment: a pilot study.
AB  - INTRODUCTION: Patients with chronic obstructive pulmonary disease (COPD)
      frequently suffer from comorbidities. COPD severity may be evaluated by the
      Global initiative for chronic Obstructive Lung Disease (GOLD) combined risk
      assessment score (GOLD score). Spirometry, body plethysmography, diffusing
      capacity of the lung for carbon monoxide (DLCO), and high-resolution computed
      tomography (HR-CT) measure lung function and elucidate pulmonary pathology. This
      study assesses associations between GOLD score and measurements of lung function
      in COPD patients with and without (<=1) comorbidities. It evaluates whether the
      presence of comorbidities influences evaluation by GOLD score of COPD severity,
      and questions whether GOLD score describes morbidity rather than COPD severity.
      METHODS: In this prospective study, 106 patients with stable COPD were included.
      Patients treated for lung cancer were excluded. Demographics, oxygen saturation
      (SpO2), modified Medical Research Council Dyspnea Scale, COPD exacerbations, and
      comorbidities were recorded. Body plethysmography and DLCO were measured, and HR
      CT performed and evaluated for emphysema and airways disease. COPD severity was
      stratified by the GOLD score. Correlation analyses: 1) GOLD score, 2) emphysema
      grade, and 3) airways disease and lung function parameters, described by: forced
      expiratory volume in the first second in percent of expected value (FEV1%),
      inspiratory capacity (IC%), total lung volume (TLC%), IC/TLC, and SpO2.
      Correlation analyses between subgroups and hierarchical cluster analysis were
      performed. RESULTS: Significant associations were found between GOLD score and
      both emphysema grade (correlation coefficients [cc]: -0.2, P=0.03) and lung
      function parameters (cc: -0.5 to -0.7, P-values all <0.001) weakened in patients
      with >1 comorbidity (cc: -0.4 to -0.5, P-values all 0.001). Significant
      differences between subgroups were found in GOLD score and both FEV1% (cc: -0.2,
      P=0.02) and IC/TLC (cc: -0.2, P=0.02). Comorbidities were associated with GOLD
      score and composite measures in hierarchical cluster analysis. CONCLUSION: The
      presence of comorbidities influences the relationship between GOLD score and lung
      function measurements. GOLD score may be more representative of morbidity than of
      COPD severity.

PMID- 25750526
TI  - Electroencephalography reveals lower regional blood perfusion and atrophy of the
      temporoparietal network associated with memory deficits and hippocampal volume
      reduction in mild cognitive impairment due to Alzheimer's disease.
AB  - BACKGROUND: An increased electroencephalographic (EEG) upper/lower alpha power
      ratio has been associated with less regional blood perfusion, atrophy of the
      temporoparietal region of the brain, and reduction of hippocampal volume in
      subjects affected by mild cognitive impairment due to Alzheimer's disease as
      compared with subjects who do not develop the disease. Moreover, EEG theta
      frequency activity is quite different in these groups. This study investigated
      the correlation between biomarkers and memory performance. METHODS: EEG
      alpha3/alpha2 power ratio and cortical thickness were computed in 74 adult
      subjects with prodromal Alzheimer's disease. Twenty of these subjects also
      underwent assessment of blood perfusion by single-photon emission computed
      tomography (SPECT). Pearson's r was used to assess the correlation between
      cortical thinning, brain perfusion, and memory impairment. RESULTS: In the higher
      alpha3/alpha2 frequency power ratio group, greater cortical atrophy and lower
      regional perfusion in the temporoparietal cortex was correlated with an increase
      in EEG theta frequency. Memory impairment was more pronounced in the magnetic
      resonance imaging group and SPECT groups. CONCLUSION: A high EEG upper/low alpha
      power ratio was associated with cortical thinning and less perfusion in the
      temporoparietal area. Moreover, atrophy and less regional perfusion were
      significantly correlated with memory impairment in subjects with prodromal
      Alzheimer's disease. The EEG upper/lower alpha frequency power ratio could be
      useful for identifying individuals at risk for progression to Alzheimer's
      dementia and may be of value in the clinical context.

PMID- 25750527
TI  - Effect of stent-assisted angioplasty on cognitive status and serum levels of
      amyloid beta in patients with intracranial and/or extracranial artery stenosis.
AB  - AIM: The study reported here aimed to examine how stent-assisted angioplasty
      affects cognitive status and serum levels of amyloid betas (Abetas) 1-40 and 1-42
      in patients with cerebral arterial stenosis. METHODS: Patients with cerebral
      arterial stenosis were given stent-assisted angioplasty plus conventional
      treatment (stent-assisted angioplasty group) or conventional treatment alone
      (control group). Cognitive status and Abeta1-40 and Abeta1-42 serum levels were
      determined before treatment and at 4 and 8 weeks after treatment. RESULTS: At 4
      weeks after treatment, cognitive status in patients with stent-assisted
      angioplasty had clearly improved. Abeta1-42 serum levels changed insignificantly
      in all patients. However, Abeta1-40 serum levels and Abeta1-40/Abeta1-42 ratio
      decreased further in patients with stent-assisted angioplasty than in patients
      who received conventional treatment (controls). Eight weeks after treatment,
      cognitive status in patients who had undergone stent-assisted angioplasty were
      continuing to improve, Abeta1-42 serum levels had begun to increase dramatically,
      and Abeta1-40 serum levels and Abeta1-40/Abeta1-42 ratio had declined further.
      CONCLUSION: Stent-assisted angioplasty could improve cognitive status and
      decrease Abeta1-40 serum levels and Abeta1-40/Abeta1-42 ratio.

PMID- 25750528
TI  - Hyperprolactinemia during antipsychotics treatment increases the level of
      coagulation markers.
AB  - OBJECTIVE: The strong association between psychiatric patients who receive
      antipsychotics and the incidence of venous thromboembolism (VTE) is known.
      Although previous reports suggest that hyperprolactinemia often increases markers
      of activated coagulation, few studies have examined the direct relationship
      between the prolactin level elevated by antipsychotics and activated markers of
      activated coagulation. METHOD: The participants included 182 patients with
      schizophrenia (male =89, female =93) who received antipsychotic treatments for at
      least 3 months. Markers of VTE (D-dimer, fibrin/fibrinogen degradation products,
      and thrombin-antithrombin complex) and serum prolactin concentrations were
      measured. RESULTS: Prolactin levels were significantly correlated with the
      logarithmic transformation of the D-dimer (r=0.320, P=0.002) and
      fibrin/fibrinogen degradation product levels (r=0.236, P=0.026) but not of the
      thrombin-antithrombin complex level (r=0.117, ns) among men. However, no
      correlations were found between the VTE markers and prolactin levels among women.
      These results were confirmed using multiple regression analyses that included
      demographic factors and antipsychotic dosages. CONCLUSION: The current study
      indicates that hyperprolactinemia is associated with an increase in markers of
      activated coagulation among men receiving antipsychotics. This finding clinically
      implies that monitoring and modulating prolactin levels among men are important
      to decrease the risk of VTE.

PMID- 25750529
TI  - A case-control proton magnetic resonance spectroscopy study confirms cerebellar
      dysfunction in benign adult familial myoclonic epilepsy.
AB  - BACKGROUND: Benign adult familial myoclonic epilepsy (BAFME) is a rare form of
      epilepsy syndrome. The pathogenesis of BAFME remains unclear, though it seems to
      involve dysfunction of the cerebellum. OBJECTIVES: The purpose of this study was
      to use proton magnetic resonance spectroscopy ((1)H-MRS) to investigate whether
      neurochemical changes underlie abnormal brain function in BAFME. METHODS: Twelve
      BAFME patients from one family and 12 age- and sex-matched healthy controls were
      enrolled in this study. The ratios of NAA/Cr, NAA/Cho, Cho/Cr, and NAA/(Cr+Cho)
      were analyzed. RESULTS: The BAFME patients exhibited a decreased N
      acetylaspartate (NAA)/choline (Cho) ratio in the cerebellar cortex, whereas there
      were no significant differences in the NAA/creatine (Cr), Cho/Cr, and
      NAA/(Cr+Cho) ratios compared with healthy controls. There were no significant
      differences in (1)H-MRS values in the frontal cortex or thalamus between the
      BAFME patients and controls. No correlation was detected between the NAA/Cho
      ratio in the cerebellar cortex and disease duration, myoclonus severity, or
      tremor severity. CONCLUSION: Our results indicate clear cerebellar dysfunction in
      BAFME. (1)H-MRS is a useful tool for the diagnosis of BAFME in combination with
      family history and electrophysiological examination.

PMID- 25750530
TI  - Korean Medication Algorithm Project for Bipolar Disorder: third revision.
AB  - OBJECTIVE: To constitute the third revision of the guidelines for the treatment
      of bipolar disorder issued by the Korean Medication Algorithm Project for Bipolar
      Disorder (KMAP-BP 2014). METHODS: A 56-item questionnaire was used to obtain the
      consensus of experts regarding pharmacological treatment strategies for the
      various phases of bipolar disorder and for special populations. The review
      committee included 110 Korean psychiatrists and 38 experts for child and
      adolescent psychiatry. Of the committee members, 64 general psychiatrists and 23
      child and adolescent psychiatrists responded to the survey. RESULTS: The
      treatment of choice (TOC) for euphoric, mixed, and psychotic mania was the
      combination of a mood stabilizer (MS) and an atypical antipsychotic (AAP); the
      TOC for acute mild depression was monotherapy with MS or AAP; and the TOC for
      moderate or severe depression was MS plus AAP/antidepressant. The first-line
      maintenance treatment following mania or depression was MS monotherapy or MS plus
      AAP; the first-line treatment after mania was AAP monotherapy; and the first-line
      treatment after depression was lamotrigine (LTG) monotherapy, LTG plus MS/AAP, or
      MS plus AAP plus LTG. The first-line treatment strategy for mania in children and
      adolescents was MS plus AAP or AAP monotherapy. For geriatric bipolar patients,
      the TOC for mania was AAP/MS monotherapy, and the TOC for depression was AAP plus
      MS or AAP monotherapy. CONCLUSION: The expert consensus in the KMAP-BP 2014
      differed from that in previous publications; most notably, the preference for AAP
      was increased in the treatment of acute mania, depression, and maintenance
      treatment. There was increased expert preference for the use of AAP and LTG. The
      major limitation of the present study is that it was based on the consensus of
      Korean experts rather than on experimental evidence.

PMID- 25750531
TI  - Minocycline upregulates cyclic AMP response element binding protein and brain
      derived neurotrophic factor in the hippocampus of cerebral ischemia rats and
      improves behavioral deficits.
AB  - BACKGROUND AND PURPOSE: The cAMP response element binding protein (CREB) plays an
      important role in the mechanism of cognitive impairment and is also pivotal in
      the switch from short-term to long-term memory. Brain-derived neurotrophic factor
      (BDNF) seems a promising avenue in the treatment of cerebral ischemia injury
      since this neurotrophin could stimulate structural plasticity and repair
      cognitive impairment. Several findings have displayed that the dysregulation of
      the CREB-BDNF cascade has been involved in cognitive impairment. The aim of this
      study was to investigate the effect of cerebral ischemia on learning and memory
      as well as on the levels of CREB, phosphorylated CREB (pCREB), and BDNF, and to
      determine the effect of minocycline on CREB, pCREB, BDNF, and behavioral
      functional recovery after cerebral ischemia. METHODS: The animal model was
      established by permanent bilateral occlusion of both common carotid arteries.
      Behavior was evaluated 5 days before decapitation with Morris water maze and open
      field task. Four days after permanent bilateral occlusion of both common carotid
      arteries, minocycline was administered by douche via the stomach for 4 weeks.
      CREB and pCREB were examined by Western blotting, reverse transcription
      polymerase chain reaction, and immunohistochemistry. BDNF was measured by
      immunohistochemistry and Western blotting. RESULTS: The model rats after
      minocycline treatment swam shorter distances than control rats before finding the
      platform (P=0.0007). The number of times the platform position was crossed for
      sham-operation rats was more than that of the model groups in the corresponding
      platform location (P=0.0021). The number of times the platform position was
      crossed for minocycline treatment animals was significantly increased compared to
      the model groups in the corresponding platform position (P=0.0016). CREB, pCREB,
      and BDNF were downregulated after permanent bilateral occlusion of both common
      carotid arteries in the model group. Minocycline increased the expression of
      CREB, pCREB, and BDNF, and improved cognitive suffered from impairment of
      permanent bilateral occlusion of both common carotid arteries. CONCLUSION:
      Minocycline improved cognitive impairment from cerebral ischemia via enhancing
      CREB, pCREB, and BDNF activity in the hippocampus.

PMID- 25750532
TI  - Toward an online cognitive and emotional battery to predict treatment remission
      in depression.
AB  - PURPOSE: To evaluate the performance of a cognitive and emotional test battery in
      a representative sample of depressed outpatients to inform likelihood of
      remission over 8 weeks of treatment with each of three common antidepressant
      medications. PATIENTS AND METHODS: Outpatients 18-65 years old with nonpsychotic
      major depressive disorder (17 sites) were randomized to escitalopram, sertraline
      or venlafaxine-XR (extended release). Participants scored >=12 on the baseline 16
      item Quick Inventory of Depressive Symptomatology - Self-Report and completed 8
      weeks of treatment. The baseline test battery measured cognitive and emotional
      status. Exploratory multivariate logistic regression models predicting remission
      (16-item Quick Inventory of Depressive Symptomatology - Self-Report score <=5 at
      8 weeks) were developed independently for each medication in subgroups stratified
      by age, sex, or cognitive and emotional test performance. The model with the
      highest cross-validated accuracy determined the participant proportion in each
      arm for whom remission could be predicted with an accuracy >=10% above chance.
      The proportion for whom a prediction could be made with very high certainty
      (positive predictive value and negative predictive value exceeding 80%) was
      calculated by incrementally increasing test battery thresholds to predict
      remission/non-remission. RESULTS: The test battery, individually developed for
      each medication, improved identification of remitting and non-remitting
      participants by >=10% beyond chance for 243 of 467 participants. The overall
      remission rates were escitalopram: 40.8%, sertraline: 30.3%, and venlafaxine-XR:
      31.1%. Within this subset for whom prediction exceeded chance, test battery
      thresholds established a negative predictive value of >=80%, which identified
      40.9% of participants not remitting on escitalopram, 77.1% of participants not
      remitting on sertraline, and 38.7% of participants not remitting on venlafaxine
      XR (all including 20% false negatives). CONCLUSION: The test battery identified
      about 50% of each medication group as being >=10% more or less likely to remit
      than by chance, and identified about 38% of individuals who did not remit with
      >=80% certainty. Clinicians might choose to avoid this specific medication in
      these particular patients.

PMID- 25750534
TI  - Optimal management of Meniere's disease.
AB  - Confusion in the nomenclature of Meniere's disease and lack of a standard
      definition of the disorder until 1995 has hampered accurate assessment of
      treatment efficacy since the presently defined disorder was first described in
      1938. The lack of a widely accepted mechanism of the disease has also delayed the
      development of rational treatments. Past treatments have focused on relieving
      elevated pressures in the hydropic ear and more recently on treatment of
      underlying migraine. Present dietary methods of control include sodium
      restriction and migraine trigger elimination. Pharmacologic treatments include
      diuretics, migraine prophylactic medications, histamine analogs, and oral
      steroids. Surgical procedures include intratympanic steroid perfusion, shunts,
      and ablative procedures when conservative treatments fail. External pressure
      devices are also used. Evidence of efficacy is lacking for most interventions
      other than ablation. At our institution, Meniere's disease is treated as a
      cerebrovascular disorder. Control of risk factors for cerebrovascular ischemia is
      combined with treatment of pressure dysfunction in the hydropic ear. Screening
      for risk factors is performed at presentation. Migraine, dyslipidemia, obesity,
      diabetes, sleep apnea, hypertension, and atherosclerosis are among the major
      factors that often require medical management. Migraine prophylactic medications,
      magnesium supplementation, sodium restriction, migraine trigger elimination,
      diuretics, anticoagulants, and antihypertensives are among the treatments used
      initially. Steroids administered orally or intratympanically are used if control
      is not achieved medically, and ablation remains the definitive treatment in
      unilateral cases experiencing treatment failure. 

PMID- 25750535
TI  - Clinical use of azelnidipine in the treatment of hypertension in Chinese
      patients.
AB  - BACKGROUND: Hypertension is the most common chronic disease and the calcium
      channel antagonist is the most popularly used antihypertensive drug in Chinese
      patients. Azelnidipine is a third generation and long-acting dihydropyridine
      calcium channel antagonist. A series of research has demonstrated that
      azelnidipine produced an effective antihypertensive effect in patients with
      essential hypertension. Now it is need to summarize clinical use of azelnidipine
      in the treatment of hypertension in Chinese patients. METHODS: Relevant
      literature was identified by performing searches in PubMed and CNKI (China
      National Knowledge Infrastructure), covering the period from January 2003 (the
      year azelnidipine was launched) to July 2014. We included studies that described
      pharmacology of azelnidipine, especially the pharmacokinetics, clinical efficacy,
      and safety and tolerability of azelnidipine in a Chinese population. The full
      text of each article was strictly reviewed, and data interpretation was
      performed. RESULTS: In Chinese healthy volunteers, a single-dose oral
      administration of azelnidipine 8-16 mg had a peak plasma concentration of 1.66
      23.06 ng/mL and time to peak plasma concentration was 2.6-4.0 hours and the area
      under the plasma concentration versus time curve from time 0 hour to 96 hours was
      17.9-429 ng/mL.h and elimination half-life was 16.0-28.0 hours. A number of
      clinical trials have demonstrated that azelnidipine produced a significant
      reduction in blood pressure in Chinese patients with mild-to-moderate
      hypertension, which was similar to that of other effective antihypertensive drugs
      such as amlodipine, zofenopril, and nifedipine. In addition to its
      antihypertensive effect, azelnidipine had other cardiovascular protective effects
      as well, like anti-oxidative action, decreasing heart rate, and improving
      systolic and diastolic function. Azelnidipine was generally well tolerated in
      Chinese patients and no severe adverse events were observed. CONCLUSION:
      Azelnidipine is effective and safe in the treatment of hypertension in Chinese
      patients.

PMID- 25750533
TI  - Advances in diagnosis and treatment of trigeminal neuralgia.
AB  - Various drugs and surgical procedures have been utilized for the treatment of
      trigeminal neuralgia (TN). Despite numerous available approaches, the results are
      not completely satisfying. The need for more contemporaneous drugs to control the
      pain attacks is a common experience. Moreover, a number of patients become drug
      resistant, needing a surgical procedure to treat the neuralgia. Nonetheless, pain
      recurrence after one or more surgical operations is also frequently seen. These
      facts reflect the lack of the precise understanding of the TN pathogenesis.
      Classically, it has been related to a neurovascular compression at the trigeminal
      nerve root entry-zone in the prepontine cistern. However, it has been evidenced
      that in the pain onset and recurrence, various neurophysiological mechanisms
      other than the neurovascular conflict are involved. Recently, the introduction of
      new magnetic resonance techniques, such as voxel-based morphometry, diffusion
      tensor imaging, three-dimensional time-of-flight magnetic resonance angiography,
      and fluid attenuated inversion recovery sequences, has provided new insight about
      the TN pathogenesis. Some of these new sequences have also been used to better
      preoperatively evidence the neurovascular conflict in the surgical planning of
      microvascular decompression. Moreover, the endoscopy (during microvascular
      decompression) and the intraoperative computed tomography with integrated
      neuronavigation (during percutaneous procedures) have been recently introduced in
      the challenging cases. In the last few years, efforts have been made in order to
      better define the optimal target when performing the gamma knife radiosurgery.
      Moreover, some authors have also evidenced that neurostimulation might represent
      an opportunity in TN refractory to other surgical treatments. The aim of this
      work was to review the recent literature about the pathogenesis, diagnosis, and
      medical and surgical treatments, and discuss the significant advances in all
      these fields. 

PMID- 25750536
TI  - Role of physiotherapy and patient education in lymphedema control following
      breast cancer surgery.
AB  - INTRODUCTION: This retrospective cohort study evaluated whether education in
      combination with physiotherapy can reduce the risk of breast cancer-related
      lymphedema (BCRL). METHODS: We analyzed 1,217 women diagnosed with unilateral
      breast cancer between January 2007 and December 2011 who underwent tumor
      resection and axillary lymph node dissection. The patients were divided into
      three groups: Group A (n=415), who received neither education nor physiotherapy
      postsurgery; Group B (n=672), who received an educational program on BCRL between
      Days 0 and 7 postsurgery; and Group C (n=130), who received an educational
      program on BCRL between Days 0 and 7 postsurgery, followed by a physiotherapy
      program. All patients were monitored until October 2013 to determine whether BCRL
      developed. BCRL risk factors were evaluated using Cox proportional hazards
      models. RESULTS: During the follow-up, 188 patients (15.4%) developed lymphedema,
      including 77 (18.6%) in Group A, 101 (15.0%) in Group B, and 10 (7.7%) in Group C
      (P=0.010). The median period from surgery to lymphedema was 0.54 years
      (interquartile range =0.18-1.78). The independent risk factors for BCRL included
      positive axillary lymph node invasion, a higher (>20) number of dissected
      axillary lymph nodes, and having undergone radiation therapy, whereas receiving
      an educational program followed by physiotherapy was a protective factor against
      BCRL (hazard ratio =0.35, 95% confidence interval =0.18-0.67, P=0.002).
      CONCLUSION: Patient education that begins within the first week postsurgery and
      is followed by physiotherapy is effective in reducing the risk of BCRL in women
      with breast cancer.

PMID- 25750537
TI  - Integrating risk minimization planning throughout the clinical development and
      commercialization lifecycle: an opinion on how drug development could be
      improved.
AB  - Pharmaceutical risk minimization programs are now an established requirement in
      the regulatory landscape. However, pharmaceutical companies have been slow to
      recognize and embrace the significant potential these programs offer in terms of
      enhancing trust with health care professionals and patients, and for providing a
      mechanism for bringing products to the market that might not otherwise have been
      approved. Pitfalls of the current drug development process include risk
      minimization programs that are not data driven; missed opportunities to
      incorporate pragmatic methods and market-based insights, outmoded tools and data
      sources, lack of rapid evaluative learning to support timely adaption, lack of
      systematic approaches for patient engagement, and questions on staffing and
      organizational infrastructure. We propose better integration of risk minimization
      with clinical drug development and commercialization work streams throughout the
      product lifecycle. We articulate a vision and propose broad adoption of
      organizational models for incorporating risk minimization expertise into the drug
      development process. Three organizational models are discussed and compared:
      outsource/external vendor, embedded risk management specialist model, and Center
      of Excellence. 

PMID- 25750538
TI  - Effectiveness and tolerability of second-line treatment with vildagliptin versus
      other oral drugs for type 2 diabetes in a real-world setting in the Middle East:
      results from the EDGE study.
AB  - BACKGROUND: Type 2 diabetes mellitus (T2DM) is a chronic progressive disease that
      requires treatment intensification with antihyperglycemic agents due to
      progressive deterioration of beta-cell function. A large observational study of
      45,868 patients with T2DM across 27 countries (EDGE) assessed the effectiveness
      and safety of vildagliptin as add-on to other oral antidiabetic drugs (OADs)
      versus other comparator OAD combinations. Here, we present results from the
      Middle East countries (Bahrain, Jordan, Kuwait, Lebanon, Oman, Palestine, and the
      United Arab Emirates). METHODS: Patients inadequately controlled with OAD
      monotherapy were eligible after the add-on treatment was chosen by the physician
      based on clinical judgment and patient need. Patients were assigned to either
      vildagliptin or comparator OADs (sulfonylureas, thiazolidinediones, glinides,
      alpha-glucosidase inhibitors, or metformin, except incretin-based therapies)
      based on the add-on therapy. The primary endpoint was the proportion of patients
      achieving a glycated hemoglobin (HbA1c) reduction of >0.3% without peripheral
      edema, hypoglycemia, discontinuation due to a gastrointestinal event, or weight
      gain>=5%. One of the secondary endpoints was the proportion of patients achieving
      HbA1c<7% without hypoglycemia or weight gain. Change in HbA1c from baseline to
      study endpoint and safety were also assessed. RESULTS: Of the 4,780 patients
      enrolled in the Middle East, 2,513 received vildagliptin and 2,267 received other
      OADs. Overall, the mean (+/-standard deviation) age at baseline was 52.1+/-10.2
      years, mean HbA1c was 8.5%+/-1.3%, and mean T2DM duration was 4.2+/-4.0 years.
      The proportion of patients achieving the primary (76.1% versus 61.6%, P<0.0001)
      and secondary (54.8% versus 29.9%, P<0.0001) endpoints was higher with
      vildagliptin than with the comparator OADs. The unadjusted odds ratios for the
      primary and secondary endpoints were 1.98 (95% confidence interval 1.75-2.25) and
      2.8 (95% confidence interval 2.5-3.2), respectively, in favor of vildagliptin.
      Vildagliptin achieved a numerically greater reduction in HbA1c (1.7%) from
      baseline versus comparator OADs (1.4%). The overall incidence of adverse events
      was comparable between studied cohorts. CONCLUSION: In real life, treatment with
      vildagliptin was associated with a higher proportion of patients with T2DM
      achieving better glycemic control without tolerability issues in the Middle East.

PMID- 25750539
TI  - Strokes in young adults: epidemiology and prevention.
AB  - Strokes in young adults are reported as being uncommon, comprising 10%-15% of all
      stroke patients. However, compared with stroke in older adults, stroke in the
      young has a disproportionately large economic impact by leaving victims disabled
      before their most productive years. Recent publications report an increased
      incidence of stroke in young adults. This is important given the fact that
      younger stroke patients have a clearly increased risk of death compared with the
      general population. The prevalence of standard modifiable vascular risk factors
      in young stroke patients is different from that in older patients. Modifiable
      risk factors for stroke, such as dyslipidemia, smoking, and hypertension, are
      highly prevalent in the young stroke population, with no significant difference
      in geographic, climatic, nutritional, lifestyle, or genetic diversity. The list
      of potential stroke etiologies among young adults is extensive. Strokes of
      undetermined and of other determined etiology are the most common types among
      young patients according to TOAST (Trial of Org 10172 in Acute Stroke Treatment)
      criteria. Prevention is the primary treatment strategy aimed at reducing
      morbidity and mortality related to stroke. Therefore, primary prevention is very
      important with regard to stroke in young adults, and aggressive treatment of risk
      factors for stroke, such as hypertension, smoking, and dyslipidemia, is
      essential. The best form of secondary stroke prevention is directed toward stroke
      etiology as well as treatment of additional risk factors. However, there is a
      lack of specific recommendations and guidelines for stroke management in young
      adults. In conclusion, strokes in young adults are a major public health problem
      and further research, with standardized methodology, is needed in order to give
      us more precise epidemiologic data. Given the increasing incidence of stroke in
      the young, there is an objective need for more research in order to reduce this
      burden. 

PMID- 25750540
TI  - Extended-release niacin/laropiprant significantly improves lipid levels in type 2
      diabetes mellitus irrespective of baseline glycemic control.
AB  - BACKGROUND: The degree of glycemic control in patients with type 2 diabetes
      mellitus (T2DM) may alter lipid levels and may alter the efficacy of lipid
      modifying agents. OBJECTIVE: Evaluate the lipid-modifying efficacy of extended
      release niacin/laropiprant (ERN/LRPT) in subgroups of patients with T2DM with
      better or poorer glycemic control. METHODS: Post hoc analysis of clinical trial
      data from patients with T2DM who were randomized 4:3 to double-blind ERN/LRPT or
      placebo (n=796), examining the lipid-modifying effects of ERN/LRPT in patients
      with glycosylated hemoglobin or fasting plasma glucose levels above and below
      median baseline levels. RESULTS: At Week 12 of treatment, ERN/LRPT significantly
      improved low-density lipoprotein cholesterol, high-density lipoprotein
      cholesterol (HDL-C), non-high-density lipoprotein cholesterol, triglycerides, and
      lipoprotein (a), compared with placebo, with equal efficacy in patients above or
      below median baseline glycemic control. Compared with placebo, over 36 weeks of
      treatment more patients treated with ERN/LRPT had worsening of their diabetes and
      required intensification of antihyperglycemic medication, irrespective of
      baseline glycemic control. Incidences of other adverse experiences were generally
      low in all treatment groups. CONCLUSION: The lipid-modifying effects of ERN/LRPT
      are independent of the degree of baseline glycemic control in patients with T2DM
      (NCT00485758).

PMID- 25750541
TI  - Assessment of selected cytokines, proteins, and growth factors in the peritoneal
      fluid of patients with ovarian cancer and benign gynecological conditions.
AB  - OBJECTIVES: The ovarian tumor microenvironment, ie, the peritoneal fluid, is an
      intriguing research subject. The goal of this study was to assess the behavior of
      selected cytokines and growth factors within the peritoneal fluid in pathologies
      associated with ascites and to assess the relationship between the levels of
      these substances and select prognostic factors of ovarian cancer. METHODS: A
      total of 74 patients were enrolled in the study, including 36 patients with
      ovarian cancer and 38 patients with benign gynecological conditions. Peritoneal
      fluid collected during surgical procedures was used to assess the levels of
      interleukin (IL)-6, IL-8, stem cell factor (SCF), dickkopf-1, growth
      differentiation factor-15 (GDF-15), tumor necrosis factor-related apoptosis
      inducing ligand (TRAIL), osteoprotegerin (OPG), osteopontin, osteonectin, and
      human epididymis protein 4. The median levels of these factors were compared
      between the two groups, and the levels of selected factors were assessed in the
      ovarian cancer group with regard to the clinical stage of cancer, tumor
      differentiation, presence of peritoneal spread and positive peritoneal fluid
      cytology results. The diagnostic value of the analyzed proteins within the
      peritoneal fluid was also assessed. RESULTS: Differences were observed between
      the patients with ovarian cancer and the patients with benign gynecological
      conditions associated with ascites with regard to the levels of IL-6, IL-8, GDF
      15, SCF, osteopontin, osteonectin, and OPG. There were no differences in dickkopf
      1, TRAIL, and human epididymis protein 4 levels between the two study groups.
      Cancer stage affected only the mean SCF and OPG levels, with lower SCF values and
      higher OPG values in advanced cancers compared to less-advanced cancers. Tumor
      differentiation was associated with significantly lower SCF values in the group
      of poorly differentiated tumors. A significant reduction in SCF values and a
      significant increase in OPG and IL-6 values were also observed within cancer cell
      positive peritoneal fluid. Peritoneal spread was associated with higher levels of
      TRAIL, osteonectin, and IL-6 in ovarian cancer patients. CONCLUSION: On the basis
      of the conducted studies, it appears that of the studied factors, GDF-15, SCF,
      and OPG deserve special attention in the context of future research on the tumor
      microenvironment. With regard to diagnostics, attention should be given primarily
      to GDF-15, IL-6, and osteonectin.

PMID- 25750542
TI  - Validation of the Memorial Sloan Kettering Cancer Center nomogram for predicting
      non-sentinel lymph node metastasis in sentinel lymph node-positive breast-cancer
      patients.
AB  - BACKGROUND: The main purpose of the study reported here was to validate the
      clinical value of the Memorial Sloan Kettering Cancer Center (MSKCC) nomogram
      that predicts non-sentinel lymph node (SLN) metastasis in SLN-positive patients
      with breast cancer. METHODS: Data on 1,576 patients who received sentinel lymph
      node biopsy (SLNB) at the Shandong Cancer Hospital from December 2001 to March
      2014 were collected in this study, and data on 509 patients with positive SLN
      were analyzed to evaluate the risk factors for non-SLN metastasis. The MSKCC
      nomogram was used to estimate the probability of non-SLN metastasis and was
      compared with actual probability after grouping into deciles. A receiver
      operating characteristic (ROC) curve was drawn and predictive accuracy was
      assessed by calculating the area under the ROC curve. RESULTS: Tumor size,
      histological grade, lymphovascular invasion, multifocality, number of positive
      SLNs, and number of negative SLNs were correlated with non-SLN metastasis
      (P<0.05) by univariate analysis. However, multivariate analysis showed that tumor
      size (P=0.039), histological grade (P=0.043), lymphovascular invasion (P=0.001),
      number of positive SLNs (P=0.001), and number of negative SLNs (P=0.000) were
      identified as independent predictors for non-SLN metastasis. The trend of actual
      probability in various decile groups was comparable to the predicted probability.
      The area under the ROC curve was 0.722. Patients with predictive values lower
      than 10% (97/492, 19.7%) had a frequency of non-SLN metastasis of 17.5% (17/97).
      CONCLUSION: The MSKCC nomogram can provide an accurate prediction of the
      probability of non-SLN metastasis, and offers a reference basis about axillary
      lymph node dissection. Axillary lymph node dissection could be avoided in
      patients with predictive values lower than 10%.

PMID- 25750543
TI  - Nimotuzumab abrogates acquired radioresistance of KYSE-150R esophageal cancer
      cells by inhibiting EGFR signaling and cellular DNA repair.
AB  - BACKGROUND: Acquired radioresistance of cancer is common after repeated
      irradiation and often leads to treatment failure. This study aimed to examine the
      effects of nimotuzumab on acquired radioresistance in human esophageal carcinoma
      cells and to investigate its underlying mechanisms. METHODS: The radioresistant
      human esophageal carcinoma cell line KYSE-150R was generated by using
      fractionated irradiation. KYSE-150R cells were pretreated with or without
      nimotuzumab before ionizing radiation. Cell growth and colony formation were
      measured to quantitate the effects of radiation. The gamma-H2AX foci assay was
      employed to determine cellular DNA-repairing capacity. The phosphorylation of key
      molecules involved in the epidermal growth factor receptor (EGFR) signaling
      pathway and cellular DNA repair was measured by Western blot analysis. RESULTS:
      Nimotuzumab enhanced radiation-induced inhibition on cell growth and clonogenic
      survival in KYSE-150R cells. The average number of gamma-H2AX foci increased in
      the irradiated cells treated with nimotuzumab. Nimotuzumab inhibited
      phosphorylation of the EGFR and its downstream molecules AKT and ERK.
      Phosphorylation of the DNA repair-related proteins DNA-PKcs, ATM, and RAD51 was
      also inhibited by nimotuzumab. CONCLUSIONS: These results indicate that
      nimotuzumab can inhibit key cancer survival mechanisms, the EGFR signaling
      pathway, and DNA repair and thereby reverse acquired radioresistance in KYSE-150R
      cell line.

PMID- 25750544
TI  - An update on PARP inhibitors for the treatment of cancer.
AB  - The development of poly (adenosine diphosphate [ADP]) ribose polymerase (PARP)
      inhibitors (PARPi) has progressed greatly over the last few years and has shown
      encouraging results in the BRCA1/2 mutation-related cancers. This article
      attempts to summarize the rationale and theory behind PARPi, the clinical trials
      already reported, as well as ongoing studies designed to determine the role of
      PARPi in patients with and without germline mutations of BRCA genes. Future plans
      for PARPi both as monotherapy and in combination with standard cytotoxics, other
      biological agents, and as radiosensitizers are also covered. The widening scope
      of PARPi adds another important targeted agent to the growing list of molecular
      inhibitors; future and ongoing trials will identify the most effective role for
      PARPi, including for patients other than BRCA germline mutation carriers. 

PMID- 25750545
TI  - Health services financing and delivery: analysis of policy options for Dubai,
      United Arab Emirates.
AB  - INTRODUCTION: A national health account (NHA) provides a systematic approach to
      mapping the flow of health sector funds within a specified health system over a
      defined time period. This article attempts to present a profile of health system
      financing in Dubai, United Arab Emirates using data from NHAs, and to compare the
      functional structures of financing schemes in Dubai with schemes in Qatar and
      selected member countries of the Organization for Economic Cooperation and
      Development (OECD). METHODS: The author analyzed secondary data published in NHAs
      of Dubai and Qatar and data collected by the OECD countries and publicly
      available from Eurostat (Statistical Office of the European Union) of 25 OECD
      countries for comparative analysis. All health financing indicators used were as
      defined in the international System of Health Accounts (SHA). RESULTS: In Dubai,
      spending on inpatient care was the highest-costing component, with 30% of current
      health expenditures (CHE). Spending on outpatient care was the second highest
      costing component and accounted for about 23% of the CHE. Household spending
      accounted for about 22% of CHE (equivalent to US$187 per capita), compared to an
      average of 20% of CHE of OECD countries. Dubai spent 0.02% of CHE on long-term
      care, compared to an average of 11% of CHE of OECD countries. Dubai spent about
      6% of CHE on prevention and public health services, compared to an average of
      3.2% of CHE of OECD countries. CONCLUSION: The findings point to potential
      opportunities for growth and improvement in several health policy issues in
      Dubai, including increasing focus and funding of preventive services; shifting
      from inpatient care to day surgery, outpatient, and home-based services and
      strengthening long-term care; and introducing cost-containment measures for
      pharmaceuticals. More investment in the translation of NHA data into policy is
      suggested for future researchers.

PMID- 25750546
TI  - The association between lower back pain and health status, work productivity, and
      health care resource use in Japan.
AB  - INTRODUCTION: This study investigated the effect of pain severity on health
      status, work productivity, health care resource use, and costs among respondents
      with lower back pain (LBP), in Japan. MATERIALS AND METHODS: Data from the 2013
      Japan National Health and Wellness Survey, a survey of Japanese adults, were
      analyzed (N=30,000). All respondents provided informed consent, and the protocol
      was institutional review board-approved. Respondents who reported experiencing
      LBP were propensity score-matched to those without LBP, based on demographics and
      health history. Using regression modeling, patients with mild, moderate, and
      severe pain were compared against matched controls, with respect to health status
      (Mental and Physical Component Summary scores, and health utilities from the
      Short Form((r))-36 Health Survey version 2), work productivity (Work Productivity
      and Activity Impairment - General Health version), health care resource use, and
      annual per-patient costs (estimated using published annual wages and resource use
      event costs). RESULTS: A total 1,897 patients reported experiencing LBP in the
      past month (6.32%); 52.45% reported their pain as mild, 32.79% as moderate, and
      14.76% as severe. Increasing pain severity was associated with significantly
      lower levels of mental component scores (46.99 [mild], 42.93 [moderate], and
      40.58 [severe] vs 48.10 [matched controls]), physical component scores (50.29
      [mild], 46.74 [moderate], and 43.94 [severe] vs 52.93 [matched controls]), and
      health utilities (0.72 [mild], 0.66 [moderate], and 0.62 [severe] vs 0.76
      [matched controls]) (all P<0.05). Indirect costs were significantly higher
      (P<0.05) among those with moderate (Y1.69 million [MM] [equivalent to $17,000,
      based on United States dollar exchange rates on September 1, 2014]) and severe
      (Y1.88 MM [$19,000]) pain, relative to matched controls (Y0.95 MM [$9,500]).
      Direct costs were only marginally different (P=0.05) between those with severe
      pain and matched controls (Y1.33 MM [$13,000] vs Y0.54 MM [$5,000]). CONCLUSION:
      Increasing pain severity among respondents with LBP was associated with
      significantly worse health status, to a clinically-relevant degree, along with
      greater indirect and direct costs, in Japan.

PMID- 25750548
TI  - Does whole-body cryotherapy improve vertical jump recovery following a high
      intensity exercise bout?
AB  - Whole-body cryotherapy (WBC) has been used as a recovery strategy following
      different sports activities. Thus, the aim of the study reported here was to
      examine the effect of WBC on vertical jump recovery following a high-intensity
      exercise (HIE) bout. Twelve trained men (mean +/- standard deviation age = 23.9+/
      5.9 years) were randomly exposed to two different conditions separated by 7 days:
      1) WBC (3 minutes of WBC at -110 degrees C immediately after the HIE) and 2)
      control (CON; no WBC after the HIE). The HIE consisted of six sets of ten
      repetitions of knee extensions at 60 degrees  . s(-1) concentric and 180 degrees 
      . s(-1) eccentric on an isokinetic dynamometer. The vertical jump test was used
      to evaluate the influence of HIE on lower extremity muscular performance. The
      vertical jump was performed on a force platform before HIE (T1) and 30 minutes
      after (T2) the WBC and CON conditions. As a result of HIE, jump height, muscle
      power, and maximal velocity (Vmax) had significant decreases between T1 and T2,
      however no significance was found between the WBC and CON conditions. The results
      indicate that one session of WBC had no effect on vertical jump following an HIE
      compared with a CON condition. WBC may not improve muscle-function (dependent on
      stretch-shortening cycle) recovery in very short periods (ie, 30 minutes)
      following HIE. 

PMID- 25750547
TI  - Carbon monoxide: a critical quantitative analysis and review of the extent and
      limitations of its second messenger function.
AB  - Endogenously produced carbon monoxide (CO) is commonly believed to be a
      ubiquitous second messenger involved in a wide range of physiological and
      pathological responses. The major evidence supporting this concept is that CO is
      produced endogenously via heme oxygenase-catalyzed breakdown of heme and that
      experimental exposure to CO alters tissue function. However, it remains to be
      conclusively demonstrated that there are specific receptors for CO and that
      endogenous CO production is sufficient to alter tissue function. Unlike other
      signaling molecules, CO is not significantly metabolized, and it is removed from
      cells solely via rapid diffusion into blood, which serves as a near infinite
      sink. This non-metabolizable nature of CO renders the physiology of this gas
      uniquely susceptible to quantitative modeling. This review analyzes each of the
      steps involved in CO signaling: 1) the background CO partial pressure (PCO) and
      the blood and tissue CO binding; 2) the affinity of the putative CO receptors; 3)
      the rate of endogenous tissue CO production; and 4) the tissue PCO that results
      from the balance between this endogenous CO production and diffusion to the blood
      sink. Because existing data demonstrate that virtually all endogenous CO
      production results from the routine "housekeeping" turnover of heme, only a small
      fraction can play a signaling role. The novel aspect of the present report is to
      demonstrate via physiological modeling that this small fraction of CO production
      is seemingly insufficient to raise intracellular PCO to the levels required for
      the conventional, specific messenger receptor activation. It is concluded that
      the many physiological alterations observed with exogenous CO administration are
      probably produced by the non-specific CO inhibition of cytochrome C oxidase
      activity, with release of reactive oxygen species (ROS) and that this ROS
      signaling pathway is a potential effector mechanism for endogenously produced CO.

PMID- 25750549
TI  - Current perspectives on attachment and bonding in the dog-human dyad.
AB  - This article reviews recent research concerning dog-human relationships and how
      attributes that arise from them can be measured. It highlights the influence of
      human characteristics on dog behavior, and consequently, the dog-human bond. Of
      particular importance are the influences of human attitudes and personality.
      These themes have received surprisingly little attention from researchers.
      Identifying human attributes that contribute to successful dog-human
      relationships could assist in the development of a behavioral template to ensure
      dyadic potential is optimized. Additionally, this article reveals how dyadic
      functionality and working performance may not necessarily be mutually inclusive.
      Potential underpinnings of various dog-human relationships and how these may
      influence dogs' perceptions of their handlers are also discussed. The article
      considers attachment bonds between humans and dogs, how these may potentially
      clash with or complement each other, and the effects of different bonds on the
      dog-human dyad as a whole. We review existing tools designed to measure the dog
      human bond and offer potential refinements to improve their accuracy. Positive
      attitudes and affiliative interactions seem to contribute to the enhanced well
      being of both species, as reflected in resultant physiological changes. Thus,
      promoting positive dog-human relationships would capitalize on these benefits,
      thereby improving animal welfare. Finally, this article proposes future research
      directions that may assist in disambiguating what constitutes successful bonding
      between dogs and the humans in their lives. 

PMID- 25750550
TI  - Stroke warning campaigns: delivering better patient outcomes? A systematic
      review.
AB  - BACKGROUND: Patient delay in presenting to hospital with stroke symptoms remains
      one of the major barriers to thrombolysis treatment, leading to its suboptimal
      use internationally. Educational interventions such as mass media campaigns and
      community initiatives aim to reduce patient delays by promoting the signs and
      symptoms of a stroke, but no consistent evidence exists to show that such
      interventions result in appropriate behavioral responses to stroke symptoms.
      METHODS: A systematic literature search and narrative synthesis were conducted to
      examine whether public educational interventions were successful in the reduction
      of patient delay to hospital presentation with stroke symptoms. Three databases,
      MEDLINE, CINAHL, and PsycINFO, were searched to identify quantitative studies
      with measurable behavioral end points, including time to hospital presentation,
      thrombolysis rates, ambulance use, and emergency department (ED) presentations
      with stroke. RESULTS: Fifteen studies met the inclusion criteria: one randomized
      controlled trial, two time series analyses, three controlled before and after
      studies, five uncontrolled before and after studies, two retrospective
      observational studies, and two prospective observational studies. Studies were
      heterogeneous in quality; thus, meta-analysis was not feasible. Thirteen studies
      examined prehospital delay, with ten studies reporting a significant reduction in
      delay times, with a varied magnitude of effect. Eight studies examined
      thrombolysis rates, with only three studies reporting a statistically significant
      increase in thrombolysis administration. Five studies examined ambulance usage,
      and four reported a statistically significant increase in ambulance transports
      following the intervention. Three studies examining ED presentations reported
      significantly increased ED presentations following intervention. Public
      educational interventions varied widely on type, duration, and content, with
      description of intervention development largely absent from studies, limiting the
      potential replication of successful interventions. CONCLUSIONS: Positive
      intervention effects were reported in the majority of studies; however,
      methodological weaknesses evident in a number of studies limited the
      generalizability of the observed effects. Reporting of specific intervention
      design was suboptimal and impeded the identification of key intervention
      components for reducing patient delay. The parallel delivery of public and
      professional interventions further limited the identification of successful
      intervention components. A lack of studies of sound methodological quality using,
      at a minimum, a controlled before and after design was identified in this review,
      and thus studies incorporating a rigorous study design are required to strengthen
      the evidence for public interventions to reduce patient delay in stroke. The
      potential clinical benefits of public interventions are far-reaching, and the
      challenge remains in translating knowledge improvements and correct behavioral
      intentions to appropriate behavior when stroke occurs.

PMID- 25750551
TI  - Prevalence of and factors associated with regular khat chewing among university
      students in Ethiopia.
AB  - PURPOSE: Khat (Catha edulis) is commonly chewed for its psychostimulant and
      euphorigenic effects in Africa and the Arabian Peninsula. Students use it to help
      them study for long hours especially during the period of examination. However,
      how regularly khat is chewed among university students and its associated factors
      are not well documented. In this article we report on the prevalence of and
      factors associated with regular khat chewing among university students in
      Ethiopia. METHODS: We did a cross-sectional study from May 20, 2014 to June 23,
      2014 on a sample of 1,255 regular students recruited from all campuses of Hawassa
      University, southern Ethiopia. The data were collected using self-administered
      questionnaires. We analyzed the data to identify factors associated with current
      regular khat chewing using complex sample adjusted logistic regression analysis.
      RESULTS: The prevalence of current regular khat chewing was 10.5% (95% confidence
      interval [CI]: 6.1%-14.9%). After controlling for sex, religion, year of study,
      having a father who chews khat, cigarette smoking and alcohol drinking in the
      adjusted logistic regression model, living off-campus in rented houses as
      compared to living in the university dormitory (adjusted odds ratio [95% CI]
      =8.09 [1.56-42.01]), and having friends who chew khat (adjusted odds ratio [95%
      CI] =4.62 [1.98-10.74]) were found to significantly increase the odds of current
      regular khat use. CONCLUSION: Students living outside the university campus in
      rented houses compared to those living in dormitory and those with khat chewing
      peers are more likely to use khat. A multipronged prevention approach involving
      students, the university officials, the surrounding community, and regulatory
      bodies is required.

PMID- 25750552
TI  - Roadmap for elimination of gastric cancer in Korea.
AB  - Most gastric cancers are caused by infection with the common human bacterial
      pathogen, Helicobacter pylori. It is now accepted that gastric cancer can be
      prevented and virtually eliminated by H. pylori eradication and this knowledge
      was responsible for country-wide H. pylori eradication combined with secondary
      cancer prevention for those with residual risk that was introduced in Japan in
      2013. Korea is a high H. pylori prevalence and high gastric cancer incidence
      country and a good candidate for a gastric cancer elimination program. The
      presence of an H. pylori infection is now considered as an indication for
      treatment of the infection. However, antimicrobial drug resistance is common
      among H. pylori in Korea making effective therapy problematic. Country-wide
      studies of the local and regional antimicrobial resistance patterns are needed to
      choose the most appropriate therapies. H. pylori and gastric cancer eradication
      can be both efficient and cost effective making it possible and practical to make
      Korea H. pylori and gastric cancer free. There is no reason to delay. 

PMID- 25750553
TI  - Microvascular angina: angina that predominantly affects women.
AB  - In women receiving evaluation for suspected ischemic symptoms, a "normal"
      diagnosis is five times more common than it is in men. These women are often
      labeled as having cardiac syndrome X, also known as microvascular angina (MVA).
      MVA is defined as angina pectoris caused by abnormalities of the small coronary
      arteries, and is characterized by effort chest pain and evidence of myocardial
      ischemia with a non-invasive stress test, although the coronary arteries can
      appear normal or near normal by angiography. MVA patients are often neglected due
      to the assumption of a good prognosis. However, MVA has important prognostic
      implications and a proper diagnosis is necessary in order to relieve the
      patients' symptoms and improve clinical outcomes. The coronary microvasculature
      cannot be directly imaged using coronary angiography, due to the small diameter
      of the vessels; therefore, the coronary microvascular must be assessed
      functionally. Treatment of MVA initially includes standard anti-ischemic drugs
      (beta-blockers, calcium antagonists, and nitrates), although control of symptoms
      is often insufficient. In this review, we discuss the pathophysiology, diagnosis,
      and treatment of MVA. 

PMID- 25750555
TI  - The simpler, the better: culprit-only intervention is beneficial in patients with
      chronic kidney disease with concurrent acute myocardial infarction and
      multivessel disease.

PMID- 25750554
TI  - Applications of systems approaches in the study of rheumatic diseases.
AB  - The complex interaction of molecules within a biological system constitutes a
      functional module. These modules are then acted upon by both internal and
      external factors, such as genetic and environmental stresses, which under certain
      conditions can manifest as complex disease phenotypes. Recent advances in high
      throughput biological analyses, in combination with improved computational
      methods for data enrichment, functional annotation, and network visualization,
      have enabled a much deeper understanding of the mechanisms underlying important
      biological processes by identifying functional modules that are temporally and
      spatially perturbed in the context of disease development. Systems biology
      approaches such as these have produced compelling observations that would be
      impossible to replicate using classical methodologies, with greater insights
      expected as both the technology and methods improve in the coming years. Here, we
      examine the use of systems biology and network analysis in the study of a wide
      range of rheumatic diseases to better understand the underlying molecular and
      clinical features. 

PMID- 25750556
TI  - Smoking cessation and chronic obstructive pulmonary disease.

PMID- 25750557
TI  - Clinical significance of Providencia bacteremia or bacteriuria.

PMID- 25750558
TI  - Long-term virological outcome in chronic hepatitis B patients with a partial
      virological response to entecavir.
AB  - BACKGROUND/AIMS: The clinical outcome of patients with a partial virological
      response (PVR) to entecavir (ETV), in particular nucloes(t)ide analogue (NA)
      experienced patients, has not been thoroughly investigated. The aim of the
      present study was to assess long-term outcomes in NA-naive and NA-experienced
      chronic hepatitis B patients with a PVR to ETV. METHODS: Chronic hepatitis B
      patients treated with ETV (0.5 mg/day) for at least 1 year were enrolled
      retrospectively. PVR was defined as a decrease in hepatitis B virus (HBV) DNA
      titer of more than 2 log10 IU/mL, yet with residual serum HBV DNA, as determined
      by real time-polymerase chain reaction, at week 48 of ETV therapy. RESULTS: A
      total of 202 patients (127 NA-naive and 75 NA-experienced, male 70.8%, antigen
      positive 53.2%, baseline serum HBV DNA 6.2 +/- 1.5 log10 IU/mL) were analyzed.
      Twenty-eight patients demonstrated a PVR. The PVR was associated with a high
      serum HBV DNA titer at baseline and at week 24. Virological response (< 60 IU/mL)
      was achieved in 46.2%, 61.5%, 77.6%, and 85% of patients with PVR at week 72, 96,
      144, and 192, respectively. Resistance to antivirals developed in two NA
      experienced patients. Failure of virological response (VR) in patients with PVR
      was associated with high levels of serum HBV DNA at week 48. CONCLUSIONS:
      Patients with PVR to ETV had favorable long-term virological outcomes. The low
      serum level of HBV DNA (< 200 IU/mL) at week 48 was associated with subsequent
      development of a VR in patients with PVR to ETV.

PMID- 25750560
TI  - Awareness of chronic obstructive pulmonary disease in current smokers: a
      nationwide survey.
AB  - BACKGROUND/AIMS: Cigarette smoking is the most common risk factor for chronic
      obstructive pulmonary disease (COPD). However, few studies of the attitudes
      toward COPD of smokers, the group at risk of developing this condition, have been
      conducted. The purpose of this study was to explore the awareness of and
      attitudes toward COPD of current smokers. METHODS: The sample consisted of 502
      individuals aged 45 and older from throughout Korea who smoked at least 10 packs
      of cigarettes per year. Telephone interviews using a structured questionnaire
      were conducted with respondents. RESULTS: First, we evaluated the health status
      of subjects, finding that 45.4% considered themselves to be in good health. We
      also asked about COPD-related symptoms, and 60.6% of subjects reported such
      symptoms. However, only 1.2% of subjects had been diagnosed with or treated for
      COPD, only 0.4% spontaneously mentioned COPD as a respiratory disease, and only
      26.5% recognized COPD as a respiratory disease after seeing a list of such
      diseases. Television ranked as the top source of information about COPD. The
      willingness of 45.0% of subjects to stop smoking increased after being informed
      about COPD. CONCLUSIONS: Despite having COPD-related symptoms, most smokers did
      not know that COPD is a respiratory disease. The attitudes of smokers toward COPD
      and smoking cessation varied according to socioeconomic status. In summary, a
      continuous effort to increase the awareness of COPD among smokers is needed.
      Additionally, strategies tailored according to different socioeconomic groups
      will also be necessary.

PMID- 25750559
TI  - Effect of revascularization strategy in patients with acute myocardial infarction
      and renal insufficiency with multivessel disease.
AB  - BACKGROUND/AIMS: The aim of this study was to compare the risk of complications
      and outcome between infarct-related artery (IRA)-only revascularization and
      multivessel (MV) revascularization in patients with acute myocardial infarction
      (MI) with renal insufficiency and MV disease. METHODS: A total of 1,031 acute MI
      patients with renal insufficiency and MV disease who were registered in the Korea
      Working Group on Myocardial Infarction were enrolled. They were divided into two
      groups (IRA-only revascularization group, n = 404; MV revascularization group, n
      = 627), and investigated the cumulative incidence of major adverse cardiac events
      (MACE) and the incidence of complications after percutaneous coronary
      intervention (PCI). RESULTS: Complications after PCI occurred in 19.9% of all
      patients (206/1,031). Complications after PCI occurred more frequently in the MV
      revascularization group compared with the IRA-only revascularization group (20.1%
      [126/627] vs. 15.3% [62/404], respectively; p = 0.029]. The overall in-hospital
      mortality rate was 6.3%, and there was no significant difference between the
      groups (5.2% in the IRA-only revascularization group vs. 7.0% in the MV
      revascularization group; p = 0.241). The total incidence of MACE was 11.1%, and
      there was no significant difference between the groups (11.6% in the IRA-only
      revascularization group vs. 10.7% in the MV revascularization group; p = 0.636).
      CONCLUSIONS: The incidence of complications after PCI was significantly lower in
      the IRA-only revascularization group compared with the MV revascularization
      group. However, there were no significant difference in the 12-month outcomes
      between groups in patients with acute MI and renal insufficiency with MV disease.

PMID- 25750561
TI  - Cutoff value of serum procalcitonin as a diagnostic biomarker of infection in end
      stage renal disease patients.
AB  - BACKGROUND/AIMS: Serum procalcitonin (PCT) levels are low in healthy individuals
      but are elevated in patients with a serious bacterial infection or sepsis. In
      this study, we examined the ability of serum PCT concentration to diagnose
      infections in end-stage renal disease (ESRD) patients, and sought to determine an
      appropriate threshold level. METHODS: Serum PCT levels were measured in ESRD
      patients on antibiotic therapy for a suspected bacterial infection (ESRD
      infection [iESRD] group, n = 21), and compared with those of ESRD patients on
      hemodialysis with no sign of infection (ESRD control [cESRD] group, n = 20).
      RESULTS: The mean serum PCT concentration of the iESRD group was significantly
      higher than in the cESRD group (2.95 +/- 3.67 ng/mL vs. 0.50 +/- 0.49 ng/mL, p =
      0.006), but serum PCT concentrations did not correlate with severity of
      infection. The optimized threshold level derived for serum PCT was 0.75 ng/mL,
      rather than the currently used 0.5 ng/mL; this threshold demonstrated a
      sensitivity and specificity of 76.2% and 80.0% for infection and 100% and 60.6%
      for systemic inflammatory response syndrome, respectively, compared with the
      cutoff of 0.5 ng/mL. CONCLUSIONS: This study suggests that serum PCT at a cutoff
      value of 0.75 ng/mL is an appropriate indicator of infection in ESRD patients.

PMID- 25750562
TI  - Relationship between duration of hospital-acquired acute kidney injury and
      mortality: a prospective observational study.
AB  - BACKGROUND/AIMS: New definitions of acute kidney injury (AKI) have recently
      emerged. Some studies have suggested that duration of AKI is an additional
      predictive parameter for mortality. Here, we evaluated whether AKI duration was
      predictive of long-term mortality in patients with hospital-acquired acute kidney
      injury (HAAKI). METHODS: We prospectively enrolled patients who developed HAAKI
      at an urban university hospital, from September 2007 to August 2008 and followed
      them until December 2011. Patients were divided into two groups by duration of
      the AKI (1 to 5 days vs. >= 6 days), and long-term mortality was compared.
      RESULTS: HAAKI developed in 1.2% of patients during the enrollment period. The
      median follow-up period was 240 days (interquartile range, 53 to 1,428). In 42.3%
      of patients (n = 52), the AKI lasted 1 to 5 days, while it lasted >= 6 days in
      57.7% (n = 71). Survival analysis showed that a longer duration of AKI increased
      the risk of death. Long-term survival was significantly different in the two
      groups. CONCLUSIONS: The duration of AKI influenced mortality rates in
      hospitalized patients. Thus, AKI duration is a parameter affecting mortality in
      HAAKI.

PMID- 25750563
TI  - Treatment of BK virus-associated hemorrhagic cystitis with low-dose intravenous
      cidofovir in patients undergoing allogeneic hematopoietic cell transplantation.
AB  - BACKGROUND/AIMS: BK virus (BKV) has been associated with late-onset hemorrhagic
      cystitis (HC) in recipients of hematopoietic stem cell transplantation (HSCT).
      Cidofovir has been used at higher doses (3 to 5 mg/kg/wk) with probenecid
      prophylaxis; however, cidofovir may result in nephrotoxicity or cytopenia at high
      doses. METHODS: Allogeneic HSCT recipients with BKV-associated HC are treated
      with 1 mg/kg intravenous cidofovir weekly at our institution. A microbiological
      response was defined as at least a one log reduction in urinary BKV viral load,
      and a clinical response was defined as improvement in symptoms and stability or
      reduction in cystitis grade. RESULTS: Eight patients received a median of 4
      weekly (range, 2 to 11) doses of cidofovir. HC occurred a median 69 days (range,
      16 to 311) after allogeneic HSCT. A clinical response was detected in 7/8
      patients (86%), and 4/5 (80%) had a measurable microbiological response. One
      patient died of uncontrolled graft-versus-host disease; therefore, we could not
      measure the clinical response to HC treatment. One microbiological non-responder
      had a stable BKV viral load with clinical improvement. Only three patients showed
      transient grade 2 serum creatinine toxicities, which resolved after completion of
      concomitant calcineurin inhibitor treatment. CONCLUSIONS: Weekly intravenous low
      dose cidofovir without probenecid appears to be a safe and effective treatment
      option for patients with BKV-associated HC.

PMID- 25750564
TI  - Clinical and microbiological features of Providencia bacteremia: experience at a
      tertiary care hospital.
AB  - BACKGROUND/AIMS: Providencia species frequently colonize urinary catheters and
      cause urinary tract infections (UTIs); however, bacteremia is uncommon and not
      well understood. We investigated the clinical features of Providencia bacteremia
      and the antibiotic susceptibility of Providencia species. METHODS: We identified
      cases of Providencia bacteremia from May 2001 to April 2013 at a tertiary care
      hospital. The medical records of pertinent patients were reviewed. RESULTS:
      Fourteen cases of Providencia bacteremia occurred; the incidence rate was 0.41
      per 10,000 admissions. The median age of the patients was 64.5 years. Eleven
      cases (78.6%) were nosocomial infections and nine cases (64.3%) were
      polymicrobial bacteremia. The most common underlying conditions were
      cerebrovascular/neurologic disease (n = 10) and an indwelling urinary catheter (n
      = 10, 71.4%). A UTI was the most common source of bacteremia (n = 5, 35.7%). The
      overall mortality rate was 29% (n = 4); in each case, death occurred within 4
      days of the onset of bacteremia. Primary bacteremia was more fatal than other
      types of bacteremia (mortality rate, 75% [3/4] vs. 10% [1/10], p = 0.041). The
      underlying disease severity, Acute Physiologic and Chronic Health Evaluation II
      scores, and Pitt bacteremia scores were significantly higher in nonsurvivors (p =
      0.016, p =0.004, and p = 0.002, respectively). Susceptibility to cefepime,
      imipenem, and piperacillin/tazobactam was noted in 100%, 86%, and 86% of the
      isolates, respectively. CONCLUSIONS: Providencia bacteremia occurred frequently
      in elderly patients with cerebrovascular or neurologic disease. Although
      Providencia bacteremia is uncommon, it can be rapidly fatal and polymicrobial.
      These characteristics suggest that the selection of appropriate antibiotic
      therapy could be complicated in Providencia bacteremia.

PMID- 25750565
TI  - Association of nasal inflammation and lower airway responsiveness in
      schoolchildren based on an epidemiological survey.
AB  - BACKGROUND/AIMS: We sought to increase our understanding of the rhinitis-asthma
      relationship and improve strategies for the treatment of patients with these
      diseases. The aim of this study was to identify a connection between upper airway
      inflammation and lower airway responsiveness. METHODS: We counted eosinophils on
      nasal smears, and performed spirometry, allergic skin tests, and methacholine
      challenge tests in 308 schoolchildren plus a questionnaire on respiratory
      symptoms. The methacholine concentration causing a 20% fall in forced expiratory
      volume in 1 second (PC20 < 25 mg/mL) was used as the threshold of bronchial
      hyperresponsiveness (BHR). RESULTS: In total, 26% of subjects had positive nasal
      eosinophils on a smear, and 46.2% of subjects had BHR at < 25 mg/mL methacholine
      PC20. Nasal symptoms were higher in subjects with than without nasal eosinophils
      (p = 0.012). Asthma symptoms did not differ between subjects with and without
      nasal eosinophils. Nasal eosinophils were higher in subjects with atopy than
      those without (p = 0.006), and there was no difference in PC20 methacholine
      according to atopy (15.5 +/- 1.07 vs. 17.5 +/- 0.62; p > 0.05). No difference in
      BHR was detected when comparing subjects with and without nasal eosinophils.
      There were significant differences in the PC20 between subjects with greater than
      50% nasal eosinophils and without nasal eosinophils (11.01 +/- 2.92 mg/mL vs.
      17.38 +/- 0.61 mg/mL; p < 0.001). CONCLUSIONS: These findings demonstrated that
      nasal eosinophilic inflammation might contribute to lower airway responsiveness
      in schoolchildren, based on an epidemiological survey.

PMID- 25750566
TI  - Pulmonary hypertension in systemic lupus erythematosus: an independent predictor
      of patient survival.
AB  - BACKGROUND/AIMS: We investigated whether transthoracic echocardiography-suspected
      pulmonary hypertension (PH) affects survival in systemic lupus erythematosus
      (SLE) patients and examined factors associated with PH occurrence and survival.
      METHODS: This retrospective single-center study included 154 Korean SLE patients
      fulfilling the American College of Rheumatology criteria (January 1995 to June
      2013). Student t test, Mann-Whitney U test, Kaplan-Meier curves, and log-rank
      tests were used for comparisons. RESULTS: A total of 35 SLE patients with PH
      (SLE/PH+) and 119 without PH (SLE/PH-) were analyzed. Higher percentages of
      interstitial lung disease, Raynaud's phenomenon (RP), World Health Organization
      functional classification III/IV, and cardiomegaly were found in SLE/PH+ compared
      to SLE/PH-. Furthermore, the Systemic Lupus International Collaborating
      Clinics/American College of Rheumatology Damage Index was significantly higher in
      SLE/PH+ (2.46 +/- 1.245 vs. 1.00 +/- 1.235), whereas survival rates were
      significantly higher in SLE/PH- in log-rank tests (p = 0.001). In multivariate
      analysis, the adjusted mortality hazard ratio (HR) for SLE/PH+ patients was 3.10.
      Subgroup analysis demonstrated a higher percentage of lupus nephritis in the
      SLE/PH+ patients who died (p = 0.039) and low complement-3 levels (p = 0.007). In
      univariate analysis, the mortality HR for SLE/PH+ patients with lupus nephritis
      was 4.62, whereas the presence of RP decreased the mortality risk in multivariate
      analysis; adjusted HR, 0.10. CONCLUSIONS: PH is an independent factor predicting
      survival in SLE patients. The presence of lupus nephritis resulted in an
      increased trend for mortality, whereas coexistence of RP was associated with a
      better survival prognosis in SLE/PH+ patients.

PMID- 25750567
TI  - Clinical characteristics of male and female Korean patients with systemic lupus
      erythematosus: a comparative study.
AB  - BACKGROUND/AIMS: To compare the clinical characteristics and outcomes of systemic
      lupus erythematosus between male and female Korean patients. METHODS: A
      retrospective analysis was performed at a single tertiary hospital from August
      1994 to May 2010. Male patients were matched with two to three female patients
      based on age and disease duration. Organ damage was assessed using the Systemic
      Lupus International Collaborating Clinics/American College of Rheumatology damage
      index (SLICC/ACR DI). RESULTS: Fifty-three male patients were compared with 150
      female patients. Renal disorders were found more frequently in male patients at
      disease onset (p < 0.001); the adjusted odds ratio (OR) demonstrated a
      significant sex preponderance for renal manifestations (OR, 3.26; 95% confidence
      interval [CI], 1.62 to 6.57). Diffuse proliferative lupus nephritis and end-stage
      renal disease requiring dialysis during the disease course were more prevalent in
      male patients (p = 0.025 and p < 0.001, respectively). The risk for requiring
      long-term dialysis was significantly higher in male than in female patients (OR,
      4.02; 95% CI, 1.07 to 15.06), as was the mean SLICC/ACR DI (1.55 +/- 1.35 vs.
      1.02 +/- 1.57, respectively; p = 0.028). CONCLUSIONS: Our data demonstrate that
      Korean patients with lupus have characteristics similar to those of cohorts
      reported previously. Male patients had significantly higher incidences of renal
      manifestations and organ damage.

PMID- 25750568
TI  - Achalasia secondary to lung adenocarcinoma.

PMID- 25750569
TI  - Spontaneous perforation and dissection of the sinus of Valsalva and
      interventricular septum with intracardiac thrombus in a patient with Behcet's
      disease.

PMID- 25750570
TI  - Development of bilateral gluteal pyomyositis during treatment of acute
      pyelonephritis in a patient with diabetes.

PMID- 25750571
TI  - Congenital nephrogenic diabetes insipidus with end-stage renal disease.

PMID- 25750572
TI  - Appropriate oral antibiotics for bone and joint infections based on the
      susceptibility of clinical Staphylococcus aureus isolates.

PMID- 25750573
TI  - A giant carotid aneurysm with intrasellar extension: a rare cause of
      panhypopituitarism.

PMID- 25750574
TI  - Intrathoracic kidney with left-sided Bochdalek hernia in a woman with bacteremic
      acute pyelonephritis due to Escherichia coli.

PMID- 25750575
TI  - Erratum: Disease burden of pneumonia in Korean adults aged over 50 years
      stratified by age and underlying diseases.
AB  - This corrects the article on p. 764 in vol. 29, PMID: 25378975.

PMID- 25750578
TI  - Decreased diastolic wall strain is associated with adverse left ventricular
      remodeling even in patients with normal left ventricular diastolic function.
AB  - BACKGROUND: The pathophysiology of diastolic dysfunction is complex, but can be
      simply described as impaired LV myocardial relaxation and/or increased LV
      stiffness. The objective of this study is to clarify true normal left ventricular
      (LV) diastolic function and early stage of diastolic dysfunction before
      relaxation abnormality develops in patients with normal LV diastolic function
      using simple diastolic wall strain (DWS) in South Korea. METHODS: DWS which is a
      non-invasive, load-independent, and reproducible estimator of LV stiffness using
      two-dimensional echocardiography using the difference between posterior wall
      thickness in systole and diastole to approximate LV stiffness. A total of 349
      consecutive patients with normal LV diastolic function by echocardiography were
      enrolled. According to DWS, patients were divided into two groups: high DWS
      (>=median 175) vs. low DWS (<median 174). RESULTS: Patients with low DWS were
      more obese and showed higher blood pressure, and had more prevalent hypertension
      and hyperlipidemia. In addition, those with low DWS had higher LV end-systolic
      volume, LV mass index, E/E' and lower ejection fraction and E' velocity. Among
      them, higher LVESV and LVMI were independently associated with low DWS.
      CONCLUSIONS: These data suggests that simple DWS might be helpful in identifying
      a subgroup of subtle diastolic dysfunction. Our data suggest that early change of
      diastolic dysfunction might start with abnormal LV geographic changes preceding
      functional changes.

PMID- 25750577
TI  - Different characteristics of heart failure due to pump failure and
      bradyarrhythmia.
AB  - BACKGROUND: Heart failure (HF) can be caused by left ventricular (LV) pump
      failure as well as by bradyarrhythmias. Hemodynamic differences between HF by LV
      pump failure and that by bradyarrhythmia have not been fully investigated. We
      hypothesized that HF by LV pump failure could be associated with both reduced
      cardiac output (CO) and increased LV filling pressure due to associated LV
      diastolic dysfunction, whereas HF by bradyarrhythmia could be associated with
      reduced CO but only modestly increased LV filling pressure due to the absence of
      LV diastolic dysfunction. METHODS: In 39 patients with HF by LV pump failure (LV
      ejection fraction <35%), 24 with HF by bradyarrhythmia, and 22 normal controls,
      LV volume, ejection fraction, stroke volume, left atrial volume, and early
      diastolic mitral valve flow to tissue annular velocity ratio (E/E') were measured
      by echocardiography. RESULTS: Compared to patients with HF by LV pump failure,
      those with HF by bradyarrhythmia had significantly lower heart rates, less LV
      dilatation, preserved LV ejection fraction, preserved stroke volume, similarly
      reduced cardiac index (1.8 +/- 0.4 vs. 1.6 +/- 0.4 L/min/m(2), n.s.), preserved
      LV diastolic function (E') (4.4 +/- 2.1 vs. 7.1 +/- 2.9 cm/s, p < 0.001), less
      dilated end-systolic LA volume, and preserved E/E' (24 +/- 10 vs. 13 +/- 7, p <
      0.001). CONCLUSIONS: HF by LV pump failure is characterized by both significantly
      reduced CO and increased LV filling pressure, whereas HF by bradyarrhythmia is
      characterized by a similar reduction in CO but only modestly increased LV filling
      pressure.

PMID- 25750579
TI  - Characterization of concentration, particle size distribution, and contributing
      factors to ambient hexavalent chromium in an area with multiple emission sources.
AB  - Airborne hexavalent chromium (Cr(VI)) is a known pulmonary carcinogen and can be
      emitted from both natural and anthropogenic sources, including diesel emissions.
      However, there is limited knowledge about ambient Cr(VI) concentration levels and
      its particle size distribution. This pilot study characterized ambient Cr(VI)
      concentrations in the New Jersey Meadowlands (NJ ML) district, which is close to
      the heavily trafficked New Jersey Turnpike (NJTPK) as well as Chromium Ore
      Processing Residue (COPR) waste sites. Monitoring was simultaneously conducted at
      two sites, William site (~50 m from NJTPK) and MERI site (~700 m from NJTPK). The
      distance between the two sites is approximately 6.2 km. Ambient Cr(VI)
      concentrations and PM2.5 mass concentrations were concurrently measured at both
      sites during summer and winter. The summer concentrations (mean +/- S.D.
      [median]), 0.13 +/- 0.06 [0.12] ng/m3 at the MERI site and 0.08 +/- 0.05 [0.07]
      ng/m3 at the William site, were all significantly higher than the winter
      concentrations, 0.02 +/- 0.01 [0.02] ng/m3 and 0.03 +/- 0.01 [0.03] ng/m3 at the
      MERI and William sites, respectively. The site difference (i.e., MERI > William)
      was observed for summer Cr(VI) concentrations; however, no differences for winter
      and pooled datasets. These results suggest higher Cr(VI) concentrations may be
      attributed from stronger atmospheric reactions such as photo-oxidation of Cr(III)
      to Cr(VI) in the summer. The Cr(VI) distribution as a function of particle size,
      ranging from 0.18 to 18 MUm, was determined at the William site. It was found
      that Cr(VI) was enriched in the particles less than 2.5 MUm in diameter (PM2.5).
      This finding suggested potential health concerns, because PM2.5 are easily
      inhaled and deposited in the alveoli. A multiple linear regression analysis
      confirmed ambient Cr(VI) concentrations were significantly affected by
      meteorological factors (i.e., temperature and humidity) and reactive
      gases/particles (i.e., O3, Fe and Mn).

PMID- 25750580
TI  - Receptive vocabulary differences in monolingual and bilingual children.
AB  - Studies often report that bilingual participants possess a smaller vocabulary in
      the language of testing than monolinguals, especially in research with children.
      However, each study is based on a small sample so it is difficult to determine
      whether the vocabulary difference is due to sampling error. We report the results
      of an analysis of 1,738 children between 3 and 10 years old and demonstrate a
      consistent difference in receptive vocabulary between the two groups. Two
      preliminary analyses suggest that this difference does not change with different
      language pairs and is largely confined to words relevant to a home context rather
      than a school context.

PMID- 25750581
TI  - Health issues of older people with intellectual disability in group homes?
AB  - BACKGROUND: This paper explores how group home staff in Victoria, Australia,
      responded to residents with an intellectual disability (ID) as they developed age
      related health conditions. METHOD: The analysis was based on a longitudinal study
      that followed 17 ageing group home residents over a 3-year period. Eighty-three
      interviews were conducted with 30 group home staff in 17 group homes. Dimensional
      analysis, a variant of grounded theory, guided data collection and analysis.
      RESULTS: Findings revealed that the organisations all had systems in place to
      address health issues. However, the results also suggest an inability of staff to
      differentiate between significant health conditions and normal age-related
      changes, thus contributing to delays in care for serious medical conditions.
      CONCLUSIONS: Lack of knowledge about normal ageing and an absence of
      organisational policies influence timeliness of diagnosis and treatment for
      people with ID. Group home staff could be more effective advocates for older
      residents, leading to improvements in health outcomes, if they had basic
      knowledge about normal ageing and symptoms of common age-related illnesses and if
      group home agencies provided clearer guidance to their staff. The study has
      implications for staff education and organisational policy development for group
      homes.

PMID- 25750582
TI  - Socioeconomic and gender group differences in early literacy skills: a multiple
      group confirmatory factor analysis approach.
AB  - Socioeconomic status and gender are important demographic variables that strongly
      relate to academic achievement. This study examined the early literacy skills
      differences between 4 sociodemographic groups, namely, boys ineligible for free
      or reduced-price lunch (FRL), girls ineligible for FRL, boys eligible for FRL,
      and girls eligible for FRL. Data on kindergarteners (N = 462) were analysed using
      multiple-group confirmatory factory analysis. Early literacy skill differences
      between boys and girls are more nuanced than previously reported; subsidy status
      and gender interact. Both boys and girls from high-poverty households performed
      significantly lower than the girls from low-poverty households in alphabet
      knowledge, phonological awareness, and spelling. There were gender gaps, with a
      female advantage, among children from high-poverty households in alphabet
      knowledge and spelling and among children from low-poverty households in alphabet
      knowledge. These results highlight the importance of employing methodologically
      sound techniques to ascertain group differences in componential early literacy
      skills.

PMID- 25750583
TI  - Inhibiting diffusion of complex contagions in social networks: theoretical and
      experimental results.
AB  - We consider the problem of inhibiting undesirable contagions (e.g. rumors, spread
      of mob behavior) in social networks. Much of the work in this context has been
      carried out under the 1-threshold model, where diffusion occurs when a node has
      just one neighbor with the contagion. We study the problem of inhibiting more
      complex contagions in social networks where nodes may have thresholds larger than
      1. The goal is to minimize the propagation of the contagion by removing a small
      number of nodes (called critical nodes) from the network. We study several
      versions of this problem and prove that, in general, they cannot even be
      efficiently approximated to within any factor rho >= 1, unless P = NP. We develop
      efficient and practical heuristics for these problems and carry out an
      experimental study of their performance on three well known social networks,
      namely epinions, wikipedia and slashdot. Our results show that these heuristics
      perform significantly better than five other known methods. We also establish an
      efficiently computable upper bound on the number of nodes to which a contagion
      can spread and evaluate this bound on many real and synthetic networks.

PMID- 25750584
TI  - A polymer encapsulation approach to prepare zwitterion-like, biocompatible
      quantum dots with wide pH and ionic stability.
AB  - A surface modification approach adopting polymer encapsulation was developed to
      prepare zwitterion-like quantum dots (ZWL-QDs). The fundamental physical,
      chemical, and biological properties of the ZWL-QDs were characterized. It is
      found that the ZWL-QDs almost preserve the quantum yield (QY) of native
      hydrophobic QDs in organic solvents, and also are compact in size (7 ~ 10 nm
      hydrodynamic diameter) and stable over wide pHs or in high salinity solutions.
      Further cellular study shows that the ZWL-QDs with a concentration less than 100
      nM have a minimal cytotoxicity and thus are biocompatible. Characterizing and
      understanding these essential properties of the ZWL-QDs are an important step
      before employing them for various applications.

PMID- 25750585
TI  - Synthesis and complexing properties of diglycol resorcinarene podands.
AB  - Synthesis of new podands from resorcinarene and diethylene glycols are reported.
      The binding properties of these podands with alkali metal cations was studied by
      means of ESI-MS. The experimental results for podands with long diethylene glycol
      arms show the stable inclusion complexes with one or two metal cations and high
      affinity for sodium and potassium ions. This podands under appropriate conditions
      can thus form a sufficiently long cavity to accommodate more than one metal ion
      inside without disturbance of the axial symmetry like an ion channel. Podand with
      shorter arms, obtained from ethylene glycol form complexes with 1:1 stoichiometry
      and also readily dimers or trimers. In the presence of alkali metal cations this
      podand selectively binds cesium ions. The significant affinity of synthesized
      podands for the biologically important alkali metal ions may affect living
      organisms. Antibacterial activities were tested with series of Gram-positive and
      Gram-negative bacteria.

PMID- 25750586
TI  - Dexmedetomidine versus remifentanil in postoperative pain control after spinal
      surgery: a randomized controlled study.
AB  - BACKGROUND: Total intravenous anesthesia (TIVA) is used widely in spinal surgery
      because inhalational anesthetics are known to decrease the amplitude of motor
      evoked potentials. Presently, dexmedetomidine is used as an adjuvant for propofol
      based TIVA. We compared the effects of remifentanil and dexmedetomidine on pain
      intensity as well as the analgesic requirements after post-anesthesia care unit
      (PACU) discharge in patients undergoing spinal surgery. METHODS: Forty patients
      scheduled for posterior lumbar interbody fusion (PLIF) surgery under general
      anesthesia were enrolled. Anesthesia was maintained using propofol at 3-12
      mg/kg/h and remifentanil at 0.01-0.2 MUg/kg/min in Remifentanil group or
      dexmedetomidine at 0.01-0.02 MUg/kg/min in Dexmedetomidine group, keeping the
      bispectral index between 40 and 60. Patient-controlled analgesia (PCA) made of
      hydromophone was applied once the patients opened their eyes in the PACU. The
      visual analog scale (VAS) score, PCA dosage administered, and postoperative
      nausea and vomiting (PONV) were recorded at the time of discharge from the PACU
      (T1) and at 2 (T2), 8 (T3), 24 (T4), and 48 hours (T5) after surgery. RESULTS:
      The VAS score in Remifentanil group was significantly higher than that in
      Dexmedetomidine group at immediate and late postoperative period (4.1 +/- 2.0 vs.
      2.3 +/- 2.2 at T1, and 4.0 +/- 2.2 vs. 2.6 +/- 1.7 at T5; P < 0.05).
      Dexmedtomidine group had a statistically significantly lower PCA requirement at
      every time point after surgery except directly before discharge from the PACU
      (3.0 +/- 1.2 ml vs. 2.3 +/- 1.4 ml at T1; P > 0.05, but 69.7 +/- 21.4 ml vs. 52.8
      +/- 10.8 ml at T5; P < 0.05). Patients in Remifentanil group displayed more PONV
      until 24 hours post-surgery. CONCLUSIONS: Dexmedetomidine displayed superior
      efficacy in alleviating pain and in postoperative pain management for 48 hours
      after PLIF. Therefore, dexmedetomidine may be used instead of remifentanil as an
      adjuvant in propofol-based TIVA. TRIAL REGISTRATION: Clinical Research
      Information Service (CRiS) Identifier: KCT0001041.

PMID- 25750587
TI  - The role of health-related claims and health-related symbols in consumer
      behaviour: Design and conceptual framework of the CLYMBOL project and initial
      results.
AB  - Health claims and symbols are potential aids to help consumers identify foods
      that are healthier options. However, little is known as to how health claims and
      symbols are used by consumers in real-world shopping situations, thus making the
      science-based formulation of new labelling policies and the evaluation of
      existing ones difficult. The objective of the European Union-funded project Role
      of health-related CLaims and sYMBOLs in consumer behaviour (CLYMBOL) is to
      determine how health-related information provided through claims and symbols, in
      their context, can affect consumer understanding, purchase and consumption. To do
      this, a wide range of qualitative and quantitative consumer research methods are
      being used, including product sampling, sorting studies (i.e. how consumers
      categorise claims and symbols according to concepts such as familiarity and
      relevance), cross-country surveys, eye-tracking (i.e. what consumers look at and
      for how long), laboratory and in-store experiments, structured interviews, as
      well as analysis of population panel data. EU Member States differ with regard to
      their history of use and regulation of health claims and symbols prior to the
      harmonisation of 2006. Findings to date indicate the need for more structured and
      harmonised research on the effects of health claims and symbols on consumer
      behaviour, particularly taking into account country-wide differences and
      individual characteristics such as motivation and ability to process health
      related information. Based on the studies within CLYMBOL, implications and
      recommendations for stakeholders such as policymakers will be provided.

PMID- 25750589
TI  - Rivaroxaban versus enoxaparin/vitamin K antagonist therapy in patients with
      venous thromboembolism and renal impairment.
AB  - BACKGROUND: Patients with renal impairment receiving classical anticoagulation
      for venous thromboembolism (VTE) are at increased risk of bleeding and possibly
      pulmonary embolism. We examined the efficacy and safety of oral rivaroxaban in
      patients with VTE with and without renal impairment. METHODS: Prespecified
      subgroup analysis of the EINSTEIN DVT and EINSTEIN PE studies comparing fixed
      dose rivaroxaban with enoxaparin/a vitamin K antagonist (VKA), performed in 8246
      patients enrolled from 2007 to 2011 in 314 hospitals. RESULTS: Outcomes were
      recurrent VTE and major or clinically relevant nonmajor bleeding in patients with
      normal renal function (n = 5569; 67.3%) or mild (n = 2037; 24.6%), moderate (n =
      636; 7.7%), or severe (n = 21; 0.3%) renal impairment. Rates of recurrent VTE
      were 1.8%, 2.8%, 3.3%, and 4.8% in patients with normal renal function and mild,
      moderate, and severe renal impairment, respectively (ptrend = 0.001). Hazard
      ratios for recurrent VTE were similar between treatment groups across renal
      function categories (pinteraction = 0.72). Major bleeding in rivaroxaban
      recipients occurred in 0.8%, 1.4%, 0.9%, and 0%, respectively (ptrend = 0.50).
      Respective rates in enoxaparin/VKA recipients were 1.0%, 3.0%, 3.9%, and 9.1%
      (ptrend < 0.001). Rivaroxaban-enoxaparin/VKA hazard ratios were 0.79 (95%
      confidence interval [CI] 0.46-1.36) for normal renal function, 0.44 (95% CI 0.24
      0.84) for mild renal impairment, and 0.23 (95% CI 0.06-0.81) for moderate renal
      impairment (pinteraction = 0.034). CONCLUSIONS: Patients with symptomatic VTE and
      renal impairment are at increased risk of recurrent VTE. Renal impairment
      increased the risk of major bleeding in enoxaparin/VKA-treated patients but not
      in rivaroxaban-treated patients. TRIAL REGISTRATION: NCT00440193 and NCT00439777.

PMID- 25750590
TI  - Where are they now? Cash and Counseling successes and challenges over time.
AB  - The positive results of the Cash & Counseling Demonstration and Evaluation (CCDE)
      led to the funding of a replication project that included 12 more states in 2008.
      Since then, the political and economic environments have changed. The authors
      sought to investigate how well the three original and 12 replication CCDE
      programs are coping with current challenges, and how their experiences may inform
      the growth and sustainability of emerging participant-directed programs.
      Semistructured telephone interviews were conducted with the 15 Cash & Counseling
      state program administrators. Key topics addressed included: successful aspects
      of state programs, biggest challenges for each program, and information program
      administrators would like to learn from state colleagues. Themes related to
      budget issues (e.g., staff shortages and program funding cuts) and non-budget
      related issues (e.g., understanding of program operations) emerged from the
      interviews. State program administrators also discussed program successes. To
      promote the sustainability and growth of participant-directed programs, existing
      participant-directed programs should be tied to national policy trends as well as
      review whether or not the programs address participant-directed principles. The
      development of new participant-directed programs should be based on other states'
      experiences as discussed in this paper.

PMID- 25750591
TI  - Dormant Masculinity: Moderating Effects of Acute Alcohol Intoxication on the
      Relation Between Male Role Norms and Antigay Aggression.
AB  - Acute alcohol intoxication was examined as a moderator of the association between
      men's adherence to traditional gender norms and aggression towards a gay male.
      Participants were 164 heterosexual drinking men between the ages of 21-30.
      Participants completed a battery of questionnaires that included a measure of
      adherence to male role norms (i.e., status, toughness, antifemininity), were
      randomly assigned to consume an alcohol or no-alcohol control beverage, and
      completed the Taylor Aggression Paradigm in which electric shocks were
      administered to, and received from, a fictitious gay or heterosexual male
      opponent. Results indicated a greater adherence to both the toughness (beta =
      .50, p = .002) and antifeminine (beta = .37, p = .023) norms predicted high
      levels of aggression towards a gay man only among participants who were
      intoxicated. This interaction effect was not detected for the status norm.
      Consistent with previous research, findings suggest that adherence to the
      toughness norm does not increase sober men's risk of aggression toward gay men.
      However, this is the first study to demonstrate that alcohol intoxication may
      activate concepts of toughness, and thus influence men to act in line with this
      facet of the masculine concept. Importantly, these data support the view that
      men's adherence to various dimensions of masculinity may be dormant in some
      contexts, only to be activated, and subsequently demonstrated, in other contexts.

PMID- 25750588
TI  - Measurement of non-VKA oral anticoagulants versus classic ones: the appropriate
      use of hemostasis assays.
AB  - Traditional anticoagulant agents such as vitamin K antagonists (VKAs),
      unfractionated heparin (UFH), low molecular weight heparins (LMWHs) and
      fondaparinux have been widely used in the prevention and treatment of
      thromboembolic diseases. However, these agents are associated with limitations,
      such as the need for regular coagulation monitoring (VKAs and UFH) or a
      parenteral route of administration (UFH, LMWHs and fondaparinux). Several non-VKA
      oral anticoagulants (NOACs) are now widely used in the prevention and treatment
      of thromboembolic diseases and in stroke prevention in non-valvular atrial
      fibrillation. Unlike VKAs, NOACs exhibit predictable pharmacokinetics and
      pharmacodynamics. They are therefore usually given at fixed doses without routine
      coagulation monitoring. However, in certain patient populations or special
      clinical circumstances, measurement of drug exposure may be useful, such as in
      suspected overdose, in patients experiencing a hemorrhagic or thromboembolic
      event during the treatment's period, in those with acute renal failure, in
      patients who require urgent surgery or in case of an invasive procedure. This
      article aims at providing guidance on laboratory testing of classic
      anticoagulants and NOACs. 

PMID- 25750592
TI  - Alcohol Use Disorders: Translational Utility of DSM-IV Liabilities to the DSM-5
      System.
AB  - OBJECTIVES: Young adults have some of the highest rates of problem drinking and
      alcohol use disorders (AUDs) relative to any other age. However, recent evidence
      suggests that the DSM-IV hierarchical classification system of AUDs does not
      validly represent symptoms in the population; instead, it evinces a unitary,
      dimensional classification scheme. The DSM-5 has been altered to fit this
      changing, evidence-based conceptualization. Nevertheless, little is understood
      about the degree to which known risk factors for DSM-IV AUD diagnoses will
      transfer to the new DSM-5 guidelines in this group of high-risk drinkers. The
      current study built a coherent model of liabilities for DSM-IV AUDs in young
      adults and tested for transferability to DSM-5. METHODS: N = 496 college students
      (51.10% male) were assessed on a variety of factors related to AUD risk,
      including demographics, substance use (past 90-days), and drinking motives.
      Liability models were created using all variables in Structural Equation Modeling
      to test direct and indirect effects on DSM diagnostic status. The best model
      under the DSM-IV was chosen based on fit and parsimony. This model was then
      applied to the DSM-5 system to test for transferability. RESULTS: The best the
      fitting model for DSM-IV included direct influences of drug use, quantity
      frequency of alcohol consumption, and social and coping drinking motives.
      Improved model fit was found when the DSM-5 system was the outcome. CONCLUSIONS:
      Knowledge of risk factors for AUDs appear to transfer well to the new diagnostic
      system.

PMID- 25750593
TI  - Systems Engineering and Point of Care Testing: Report from the NIBIB POCT/Systems
      Engineering Workshop.
AB  - The first part of this manuscript is an introduction to systems engineering and
      how it may be applied to health care and point of care testing (POCT). Systems
      engineering is an interdisciplinary field that seeks to better understand and
      manage changes in complex systems and projects as whole. Systems are sets of
      interconnected elements which interact with each other, are dynamic, change over
      time and are subject to complex behaviors. The second part of this paper reports
      on the results of the National Institute of Biomedical Imaging and Bioengineering
      (NIBIB) workshop exploring the future of point of care testing and technologies
      and the recognition that these new technologies do not exist in isolation. That
      they exist within ecosystems of other technologies and systems; and these systems
      influence their likelihood of success or failure and their effectiveness. In this
      workshop, a diverse group of individuals from around the country, from
      disciplines ranging from clinical care, engineering, regulatory affairs and many
      others to members of the three major National Institutes of Health (NIH) funded
      efforts in the areas the Centers for POCT for sexually transmitted disease, POCT
      for the future of Cancer Care, POCT primary care research network, gathered
      together for a modified deep dive workshop exploring the current state of the
      art, mapping probable future directions and developing longer term goals. The
      invitees were broken up into 4 thematic groups: Home, Outpatient, Public/shared
      space and Rural/global. Each group proceeded to explore the problem and solution
      space for point of care tests and technology within their theme. While each
      thematic area had specific challenges, many commonalities also emerged. This
      effort thus helped create a conceptual framework for POCT as well as identifying
      many of the challenges for POCT going forward. Four main dimensions were
      identified as defining the functional space for both point of care testing and
      treatment, these are: Time, Location, Interpretation and Tempo. A framework is
      presented in this paper. There were several current and future challenges
      identified through the workshop. These broadly fall into the categories of
      technology development and implementation. More specifically these are in the
      areas of: 1) Design, 2) Patient driven demand and technology, 3) Information
      Characteristics and Presentation, 4) Health Information Systems, 5) Connectivity,
      6) Workflow and implementation, 7) Maintenance/Cost, and 8) Quality Control.
      Definitions of these challenge areas and recommendations to address them are
      provided.

PMID- 25750594
TI  - Integration of Network Biology and Imaging to Study Cancer Phenotypes and
      Responses.
AB  - Ever growing "omics" data and continuously accumulated biological knowledge
      provide an unprecedented opportunity to identify molecular biomarkers and their
      interactions that are responsible for cancer phenotypes that can be accurately
      defined by clinical measurements such as in vivo imaging. Since signaling or
      regulatory networks are dynamic and context-specific, systematic efforts to
      characterize such structural alterations must effectively distinguish significant
      network rewiring from random background fluctuations. Here we introduced a novel
      integration of network biology and imaging to study cancer phenotypes and
      responses to treatments at the molecular systems level. Specifically,
      Differential Dependence Network (DDN) analysis was used to detect statistically
      significant topological rewiring in molecular networks between two phenotypic
      conditions, and in vivo Magnetic Resonance Imaging (MRI) was used to more
      accurately define phenotypic sample groups for such differential analysis. We
      applied DDN to analyze two distinct phenotypic groups of breast cancer and study
      how genomic instability affects the molecular network topologies in high-grade
      ovarian cancer. Further, FDA-approved arsenic trioxide (ATO) and the ND2-SmoA1
      mouse model of Medulloblastoma (MB) were used to extend our analyses of combined
      MRI and Reverse Phase Protein Microarray (RPMA) data to assess tumor responses to
      ATO and to uncover the complexity of therapeutic molecular biology. 

PMID- 25750596
TI  - Assessing the Effectiveness of Breast Cancer Education Workshops among Samoan and
      Pacific Islander Women in Southern California.
AB  - BACKGROUND: Samoans experience among the worst five-year breast cancer survival
      rates in the U.S., largely due to late stage diagnosis. There is great potential
      for screening interventions to reduce cancer mortality among Samoans. This paper
      examines the effectiveness of a culturally and linguistically tailored breast
      cancer education workshop for Samoan and other Pacific Islander women in Southern
      California. METHODS: Educational workshops were conducted in churches, homes, and
      the Samoan National Nurses Association office to Pacific Islander women.
      Effectiveness was assessed using pre- and post-tests. Self-administered
      questionnaires queried participants about demographics, access, personal or
      family breast cancer history, screening knowledge and behaviors, and plans to
      obtain screening (n=495). RESULTS: Participants were predominantly Samoan, with
      57% reporting they were >=40 years of age. At pre-test, half of the participants
      did not know how to perform Breast Self Examination (BSE), 40% never had a
      Clinical Breast Examination (CBE), and 30% never had a mammogram. Less than 40%
      reported having a mammogram in the past two years. At post-test, 98% reported
      increased knowledge. Older women were more likely to report plans for screening
      at post-test. CONCLUSIONS: Health educators in Samoan and other Pacific Islander
      communities must recognize and appropriately address screening barriers such as
      cultural beliefs and lack of knowledge, and should consider working with
      important institutions such as the church.

PMID- 25750595
TI  - A Deep Learning Network Approach to ab initio Protein Secondary Structure
      Prediction.
AB  - Ab initio protein secondary structure (SS) predictions are utilized to generate
      tertiary structure predictions, which are increasingly demanded due to the rapid
      discovery of proteins. Although recent developments have slightly exceeded
      previous methods of SS prediction, accuracy has stagnated around 80 percent and
      many wonder if prediction cannot be advanced beyond this ceiling. Disciplines
      that have traditionally employed neural networks are experimenting with novel
      deep learning techniques in attempts to stimulate progress. Since neural networks
      have historically played an important role in SS prediction, we wanted to
      determine whether deep learning could contribute to the advancement of this field
      as well. We developed an SS predictor that makes use of the position-specific
      scoring matrix generated by PSI-BLAST and deep learning network architectures,
      which we call DNSS. Graphical processing units and CUDA software optimize the
      deep network architecture and efficiently train the deep networks. Optimal
      parameters for the training process were determined, and a workflow comprising
      three separately trained deep networks was constructed in order to make refined
      predictions. This deep learning network approach was used to predict SS for a
      fully independent test dataset of 198 proteins, achieving a Q3 accuracy of 80.7
      percent and a Sov accuracy of 74.2 percent. 

PMID- 25750597
TI  - Ergogenic effects of caffeine and sodium bicarbonate supplementation on
      intermittent exercise performance preceded by intense arm cranking exercise.
AB  - BACKGROUND: Caffeine and sodium bicarbonate ingestion have been suggested to
      improve high-intensity intermittent exercise, but it is unclear if these
      ergogenic substances affect performance under provoked metabolic acidification.
      To study the effects of caffeine and sodium bicarbonate on intense intermittent
      exercise performance and metabolic markers under exercise-induced acidification,
      intense arm-cranking exercise was performed prior to intense intermittent running
      after intake of placebo, caffeine and sodium bicarbonate. METHODS: Male team
      sports athletes (n = 12) ingested sodium bicarbonate (NaHCO3; 0.4 g.kg(-1) b.w.),
      caffeine (CAF; 6 mg.kg(-1) b.w.) or placebo (PLA) on three different occasions.
      Thereafter, participants engaged in intense arm exercise prior to the Yo-Yo
      intermittent recovery test level-2 (Yo-Yo IR2). Heart rate, blood lactate and
      glucose as well as rating of perceived exertion (RPE) were determined during the
      protocol. RESULTS: CAF and NaHCO3 elicited a 14 and 23% improvement (P < 0.05),
      respectively, in Yo-Yo IR2 performance, post arm exercise compared to PLA. The
      NaHCO3 trial displayed higher [blood lactate] (P < 0.05) compared to CAF and PLA
      (10.5 +/- 1.9 vs. 8.8 +/- 1.7 and 7.7 +/- 2.0 mmol.L(-1), respectively) after the
      Yo-Yo IR2. At exhaustion CAF demonstrated higher (P < 0.05) [blood glucose]
      compared to PLA and NaHCO3 (5.5 +/- 0.7 vs. 4.2 +/- 0.9 vs. 4.1 +/- 0.9 mmol.L(
      1), respectively). RPE was lower (P < 0.05) during the Yo-Yo IR2 test in the
      NaHCO3 trial in comparison to CAF and PLA, while no difference in heart rate was
      observed between trials. CONCLUSIONS: Caffeine and sodium bicarbonate
      administration improved Yo-Yo IR2 performance and lowered perceived exertion
      after intense arm cranking exercise, with greater overall effects of sodium
      bicarbonate intake.

PMID- 25750598
TI  - Pluralism as Outcome: The Ecology of Religious Resources, Suppliers, and
      Consumers.
AB  - A great deal of interest has surrounded the topic of religious pluralism and the
      effects of the frequently used pluralism index on outcomes such as religious
      participation rates. But surprisingly little work has tried to understand the
      sources of pluralism or what the pluralism index is actually measuring. In an
      attempt to reframe the debate, we treat pluralism as an outcome variable. Drawing
      on ideas in the organizational ecology literature and data from previous studies
      on pluralism and participation, we show that the pluralism of religious suppliers
      is a product of the pluralism of religious preferences and the number of
      potential adherents within an environment. This pluralism of suppliers, in turn,
      produces a pluralism of religious consumers. We then distinguish between expected
      pluralism and observed pluralism, and we argue that a relationship between
      pluralism and participation will be expected only when a meaningful gap between
      these two measures exists. We close by examining the previous research to show
      how this reframing of the pluralism and participation question sheds light on
      that literature.

PMID- 25750599
TI  - Sleep in the Context of   Healthy Aging and   Psychiatric Syndromes.
AB  - Humans spend approximately one-third of their lives asleep. Whether due to
      evolutionary or ontogenetic factors, sleep and psychiatric disorders change with
      age. Although much of sleep remains an enigma, sleep research is experiencing an
      exponential increase in its understanding of the causes, correlates, and
      consequences of sleep disturbances. Although the relationship between age-related
      sleep and psychiatric conditions is a common clinical observation, empirical
      investigations remain scarce. Thus, treating patients with symptoms of sleep
      disorders in the context of psychiatric conditions remains a challenge. This
      article reviews the state-of-the-science of sleep disorders in the context of
      psychiatric conditions in late-life.

PMID- 25750600
TI  - Interventions for Sleep   Disturbance in Bipolar   Disorder.
AB  - Bipolar disorder is a severe and chronic disorder, ranked in the top 10 leading
      causes of disability worldwide. Sleep disturbances are strongly coupled with
      interepisode dysfunction and symptom worsening in bipolar disorder. Experimental
      studies suggest that sleep deprivation can trigger manic relapse. There is
      evidence that sleep deprivation can have an adverse impact on emotion regulation
      the following day. The clinical management of the sleep disturbances experienced
      by bipolar patients, including insomnia, hypersomnia delayed sleep phase, and
      irregular sleep-wake schedule, may include medication approaches, psychological
      interventions, light therapies and sleep deprivation.

PMID- 25750601
TI  - Pattern-mixture-type Estimation and Testing of Neuroblastoma Treatment Regimes.
AB  - Sequentially randomized designs are commonly used in biomedical research,
      particularly in clinical trials, to assess and compare the effects of different
      treatment regimes. In such designs, eligible patients are first randomized to one
      of the initial therapies, then patients with some intermediate response (e.g.
      without progressive diseases) are randomized to one of the maintenance therapies.
      The goal is to evaluate dynamic treatment regimes consisting of an initial
      therapy, the intermediate response, and a maintenance therapy. In this article,
      we demonstrate the use of pattern-mixture model (commonly used for analyzing
      missing data) for estimating the effects of treatment regimes based on familiar
      survival analysis techniques such as Nelson-Aalen and parametric models.
      Moreover, we demonstrate how to use estimates from pattern-mixture models to test
      for the differences across treatment regimes in a weighted log-rank setting. We
      investigate the properties of the proposed estimators and test in a Monte Carlo
      simulation study. Finally we demonstrate the methods using the long-term survival
      data from the high risk neuroblastoma study.

PMID- 25750603
TI  - Metabolic profiling of a transgenic Caenorhabditis elegans Alzheimer model.
AB  - Despite decades of research, no early-onset biomarkers are currently available
      for Alzheimer's disease, a cureless neurodegenerative disease afflicting millions
      worldwide. In this study, transgenic Caenorhabditis elegans were used to
      investigate changes in the metabolome after induced expression of amyloid-beta.
      GC- and LC-MS-based platforms determined a total of 157 differential features.
      Some of these were identified using in-house (GC-MS) or public libraries (LC-MS),
      revealing changes in allantoin, cystathionine and tyrosine levels. Since C.
      elegans is far better suited to metabolomics studies than most other model
      systems, the accordance of these findings with vertebrate literature is promising
      and argues for further use of C. elegans as a model of human pathology in the
      study of AD.

PMID- 25750602
TI  - A 'rule of 0.5' for the metabolite-likeness of approved pharmaceutical drugs.
AB  - We exploit the recent availability of a community reconstruction of the human
      metabolic network ('Recon2') to study how close in structural terms are marketed
      drugs to the nearest known metabolite(s) that Recon2 contains. While other
      encodings using different kinds of chemical fingerprints give greater
      differences, we find using the 166 Public MDL Molecular Access (MACCS) keys that
      90 % of marketed drugs have a Tanimoto similarity of more than 0.5 to the
      (structurally) 'nearest' human metabolite. This suggests a 'rule of 0.5' mnemonic
      for assessing the metabolite-like properties that characterise successful,
      marketed drugs. Multiobjective clustering leads to a similar conclusion, while
      artificial (synthetic) structures are seen to be less human-metabolite-like. This
      'rule of 0.5' may have considerable predictive value in chemical biology and drug
      discovery, and may represent a powerful filter for decision making processes.

PMID- 25750605
TI  - Network Analysis of Functional Brain Connectivity Driven by Gamma-Band Auditory
      Steady-State Response in Auditory Hallucinations.
AB  - The auditory steady-state response (ASSR) may reflect activity from different
      regions of the brain. Particularly, it was reported that the gamma-band ASSR
      plays an important role in working memory, speech understanding, and recognition.
      Traditionally, the ASSR has been determined by power spectral density analysis,
      which cannot detect the exact overall distributed properties of the ASSR.
      Functional network analysis has recently been applied in electroencephalography
      studies. Previous studies on resting or working state found a small-world
      organization of the brain network. Some researchers have studied dysfunctional
      networks caused by diseases. The present study investigates the brain connection
      networks of schizophrenia patients with auditory hallucinations during an ASSR
      task. A directed transfer function is utilized to estimate the brain connectivity
      patterns. Moreover, the structures of brain networks are analyzed by converting
      the connectivity matrices into graphs. It is found that for normal subjects,
      network connections are mainly distributed at the central and frontal-temporal
      regions. This indicates that the central regions act as transmission hubs of
      information under ASSR stimulation. For patients, network connections seem
      unordered. The finding that the path length was larger in patients compared to
      that in normal subjects under most thresholds provides insight into the
      structures of connectivity patterns. The results suggest that there are more
      synchronous oscillations that cover a long distance on the cortex but a less
      efficient network for patients with auditory hallucinations.

PMID- 25750606
TI  - Effect of Congenital Anomalies of the Papillary Muscles on Mitral Valve Function.
AB  - Parachute mitral valves (PMVs) and parachute-like asymmetric mitral valves
      (PLAMVs) are associated with congenital anomalies of the papillary muscles.
      Current imaging modalities cannot provide detailed biomechanical information.
      This study describes computational evaluation techniques based on three
      dimensional (3D) echocardiographic data to determine the biomechanical and
      physiologic characteristics of PMVs and PLAMVs. The closing and opening mechanics
      of a normal mitral valve (MV), two types of PLAMV with different degrees of
      asymmetry, and a true PMV were investigated. MV geometric data in a patient with
      a normal MV was acquired from 3D echocardiography. The pathologic MVs were
      modeled by altering the configuration of the papillary muscles in the normal MV
      model. Dynamic finite element simulations of the normal MV, PLAMVs, and true PMV
      were performed. There was a strong correlation between the reduction of mitral
      orifice size and the degree of asymmetry of the papillary muscle location. The
      PLAMVs demonstrated decreased leaflet coaptation and tenting height. The true PMV
      revealed severely wrinkled leaflet deformation and narrowed interchordal spaces,
      leading to uneven leaflet coaptation. There were considerable decreases in
      leaflet coaptation and abnormal leaflet deformation corresponding to the
      anomalous location of the papillary muscle tips. This computational MV evaluation
      strategy provides a powerful tool to better understand biomechanical and
      pathophysiologic MV abnormalities.

PMID- 25750604
TI  - Mechanical Impedance and Its Relations to Motor Control, Limb Dynamics, and
      Motion Biomechanics.
AB  - The concept of mechanical impedance represents the interactive relationship
      between deformation kinematics and the resulting dynamics in human joints or
      limbs. A major component of impedance, stiffness, is defined as the ratio between
      the force change to the displacement change and is strongly related to muscle
      activation. The set of impedance components, including effective mass, inertia,
      damping, and stiffness, is important in determining the performance of the many
      tasks assigned to the limbs and in counteracting undesired effects of applied
      loads and disturbances. Specifically for the upper limb, impedance enables
      controlling manual tasks and reaching motions. In the lower limb, impedance is
      responsible for the transmission and attenuation of impact forces in tasks of
      repulsive loadings. This review presents an updated account of the works on
      mechanical impedance and its relations with motor control, limb dynamics, and
      motion biomechanics. Basic questions related to the linearity and nonlinearity of
      impedance and to the factors that affect mechanical impedance are treated with
      relevance to upper and lower limb functions, joint performance, trunk stability,
      and seating under dynamic conditions. Methods for the derivation of mechanical
      impedance, both those for within the system and material-structural approaches,
      are reviewed. For system approaches, special attention is given to methods aimed
      at revealing the correct and sufficient degree of nonlinearity of impedance. This
      is particularly relevant in the design of spring-based artificial legs and
      robotic arms. Finally, due to the intricate relation between impedance and muscle
      activity, methods for the explicit expression of impedance of contractile tissue
      are reviewed.

PMID- 25750608
TI  - Living longer, working longer: the need for a comprehensive approach to labour
      market reform in response to demographic changes.

PMID- 25750607
TI  - Impact of Haemodialysis on Insulin Kinetics of Acute Kidney Injury Patients in
      Critical Care.
AB  - Critically ill patients are occasionally associated with an abrupt decline in
      renal function secondary to their primary diagnosis. The effect and impact of
      haemodialysis (HD) on insulin kinetics and endogenous insulin secretion in
      critically ill patients remains unclear. This study investigates the insulin
      kinetics of patients with severe acute kidney injury (AKI) who required HD
      treatment and glycaemic control (GC). Evidence shows that tight GC benefits the
      onset and progression of renal involvement in precocious phases of diabetic
      nephropathy for type 2 diabetes. The main objective of GC is to reduce
      hyperglycaemia while determining insulin sensitivity. Insulin sensitivity (SI )
      is defined as the body response to the effects of insulin by lowering blood
      glucose levels. Particularly, this study used SI to track changes in insulin
      levels during HD therapy. Model-based insulin sensitivity profiles were
      identified for 51 critically ill patients with severe AKI on specialized relative
      insulin nutrition titration GC during intervals on HD (OFF/ON) and after HD
      (ON/OFF). The metabolic effects of HD were observed through changes in SI over
      the ON/OFF and OFF/ON transitions. Changes in model-based SI at the OFF/ON and
      ON/OFF transitions indicate changes in endogenous insulin secretion and/or
      changes in effective insulin clearance. Patients exhibited a median reduction of 
      29 % (interquartile range (IQR): [-58, 6 %], p = 0.02) in measured SI after the
      OFF/ON dialysis transition, and a median increase of +9 % (IQR -15 to 28 %, p =
      0.7) after the ON/OFF transition. Almost 90 % of patients exhibited decreased SI
      at the OFF/ON transition, and 55 % exhibited increased SI at the ON/OFF
      transition. Results indicate that HD commencement has a significant effect on
      insulin pharmacokinetics at a cohort and per-patient level. These changes in
      metabolic behaviour are most likely caused by changes in insulin clearance or/and
      endogenous insulin secretion.

PMID- 25750609
TI  - Targeting of Cancer Cells Using Quantum Dot-Polypeptide Hybrid Assemblies that
      Function as Molecular Imaging Agents and Carrier Systems.
AB  - We report a highly tunable quantum dot (QD)-polypeptide hybrid assembly system
      with potential uses for both molecular imaging and delivery of biomolecular cargo
      to cancer cells. In this work, we demonstrate the tunability of the assembly
      system, its application for imaging cancer cells, and its ability to carry a
      biomolecule. The assemblies are formed through the self-assembly of carboxyl
      functionalized QDs and poly(diethylene glycol-L-lysine)-poly(L-lysine) (PEGLL
      PLL) diblock copolypeptide molecules, and they are modified with peptide ligands
      containing a cyclic arginine-glycine-aspartate [c(RGD)] motif that has affinity
      for alphavbeta3 and alphavbeta5 integrins overexpressed on the tumor vasculature.
      To illustrate the tunability of the QD-polypeptide assembly system, we show that
      binding to U87MG glioblastoma cells can be modulated and optimized by changing
      either the conditions under which the assemblies are formed or the relative
      lengths of the PEGLL and PLL blocks in the PEGLL-PLL molecules. The optimized
      c(RGD)-modified assemblies bind integrin receptors on U87MG cells and are
      endocytosed, as demonstrated by flow cytometry and live-cell imaging. Binding
      specificity is confirmed by competition with an excess of free c(RGD) peptide.
      Finally, we show that the QD-polypeptide assemblies can be loaded with
      fluorescently labeled ovalbumin, as a proof-of-concept for their potential use in
      biomolecule delivery.

PMID- 25750610
TI  - Tenogenic Induction of Human MSCs by Anisotropically Aligned Collagen
      Biotextiles.
AB  - A novel biofabrication modality, electrophoretic compaction with macromolecular
      alignment, was utilized to make collagen threads that mimic the native tendon's
      structure and mechanical properties. A device with kinematic electrodes was
      designed to fabricate collagen threads in continuous length. For the first time,
      a 3D-biotextile was woven purely from collagen. Mechanical properties and load
      displacement behavior of the biotextile mimicked those of the native tendon while
      presenting a porosity of 80%. The open pore network facilitated cell seeding
      across the continuum of the bioscaffold. Mesenchymal stem cells (MSCs) seeded in
      the woven scaffold underwent tenogenic differentiation in the absence of growth
      factors and synthesized a matrix that was positive for tenomodulin, COMP and type
      I collagen. Up-regulation of tenomodulin, a tendon specific marker, was 11.6 +/-
      3.5 fold, COMP was up-regulated 16.7 +/- 5.5 fold, and Col I was up-regulated 6.9
      +/- 2.7 fold greater on ELAC threads when compared to randomly oriented collagen
      gels. These results demonstrate that a bioscaffold woven by using collagen
      threads with densely compacted and anisotropically aligned substrate texture
      stimulates tenogenesis topographically, rendering the electrochemically aligned
      collagen as a promising candidate for functional repair of tendons and ligaments.

PMID- 25750612
TI  - Assessing parameter identifiability for dynamic causal modeling of fMRI data.
AB  - Deterministic dynamic causal modeling (DCM) for fMRI data is a sophisticated
      approach to analyse effective connectivity in terms of directed interactions
      between brain regions of interest. To date it is difficult to know if acquired
      fMRI data will yield precise estimation of DCM parameters. Focusing on parameter
      identifiability, an important prerequisite for research questions on directed
      connectivity, we present an approach inferring if parameters of an envisaged DCM
      are identifiable based on information from fMRI data. With the freely available
      "attention to motion" dataset, we investigate identifiability of two DCMs and
      show how different imaging specifications impact on identifiability. We used the
      profile likelihood, which has successfully been applied in systems biology, to
      assess the identifiability of parameters in a DCM with specified scanning
      parameters. Parameters are identifiable when minima of the profile likelihood as
      well as finite confidence intervals for the parameters exist. Intermediate epoch
      duration, shorter TR and longer session duration generally increased the
      information content in the data and thus improved identifiability. Irrespective
      of biological factors such as size and location of a region, attention should be
      paid to densely interconnected regions in a DCM, as those seem to be prone to non
      identifiability. Our approach, available in the DCMident toolbox, enables to
      judge if the parameters of an envisaged DCM are sufficiently determined by
      underlying data without priors as opposed to primarily reflecting the Bayesian
      priors in a SPM-DCM. Assessments with the DCMident toolbox prior to a study will
      lead to improved identifiability of the parameters and thus might prevent
      suboptimal data acquisition. Thus, the toolbox can be used as a preprocessing
      step to provide immediate statements on parameter identifiability. 

PMID- 25750613
TI  - Transcriptomic analysis and 3D bioengineering of astrocytes indicate ROCK
      inhibition produces cytotrophic astrogliosis.
AB  - Astrocytes provide trophic, structural and metabolic support to neurons, and are
      considered genuine targets in regenerative neurobiology, as their phenotype
      arbitrates brain integrity during injury. Inhibitors of Rho kinase (ROCK) cause
      stellation of cultured 2D astrocytes, increased L-glutamate transport, augmented
      G-actin, and elevated expression of BDNF and anti-oxidant genes. Here we further
      explored the signposts of a cytotrophic, "healthy" phenotype by data-mining of
      our astrocytic transcriptome in the presence of Fasudil. Gene expression profiles
      of motor and autophagic cellular cascades and inflammatory/angiogenic responses
      were all inhibited, favoring adoption of an anti-migratory phenotype. Like ROCK
      inhibition, tissue engineered bioscaffolds can influence the extracellular
      matrix. We built upon our evidence that astrocytes maintained on 3D poly-epsilon
      caprolactone (PCL) electrospun scaffolds adopt a cytotrophic phenotype similar to
      that produced by Fasudil. Using these procedures, employing mature 3D cultured
      astrocytes, Fasudil (100 MUM) or Y27632 (30 MUM) added for the last 72 h of
      culture altered arborization, which featured numerous additional minor processes
      as shown by GFAP and AHNAK immunolabelling. Both ROCK inhibitors decreased F
      actin, but increased G-actin labeling, indicative of disassembly of actin stress
      fibers. ROCK inhibitors provide additional beneficial effects for bioengineered
      3D astrocytes, including enlargement of the overall arbor. Potentially, the
      combined strategy of bio-compatible scaffolds with ROCK inhibition offers unique
      advantages for the management of glial scarring. Overall these data emphasize
      that manipulation of the astrocyte phenotype to achieve a "healthy biology"
      offers new hope for the management of inflammation in neuropathologies. 

PMID- 25750615
TI  - Buffer mobility and the regulation of neuronal calcium domains.
AB  - The diffusion of calcium inside neurons is determined in part by the
      intracellular calcium binding species that rapidly bind to free calcium ions upon
      entry. It has long been known that some portion of a neuron's intracellular
      calcium binding capacity must be fixed or poorly mobile, as calcium diffusion is
      strongly slowed in the intracellular environment relative to diffusion in
      cytosolic extract. The working assumption was that these immobile calcium binding
      sites are provided by structural proteins bound to the cytoskeleton or
      intracellular membranes and may thereby be relatively similar in composition and
      capacity across different cell types. However, recent evidence suggests that the
      immobile buffering capacity can vary greatly between cell types and that some
      mobile calcium binding proteins may alter their mobility upon binding calcium,
      thus blurring the line between mobile and immobile. The ways in which immobile
      buffering capacity might be relevant to different calcium domains within neurons
      has been explored primarily through modeling. In certain regimes, the presence of
      immobile buffers and the interaction between mobile and immobile buffers have
      been shown to result in complex spatiotemporal patterns of free calcium. In
      total, these experimental and modeling findings call for a more nuanced
      consideration of the local intracellular calcium microenvironment. In this review
      we focus on the different amounts, affinities, and mobilities of immobile calcium
      binding species; propose a new conceptual category of physically diffusible but
      functionally immobile buffers; and discuss how these buffers might interact with
      mobile calcium binding partners to generate characteristic calcium domains. 

PMID- 25750614
TI  - Epigenetic regulation in the inner ear and its potential roles in development,
      protection, and regeneration.
AB  - The burgeoning field of epigenetics is beginning to make a significant impact on
      our understanding of tissue development, maintenance, and function. Epigenetic
      mechanisms regulate the structure and activity of the genome in response to
      intracellular and environmental cues that direct cell-type specific gene
      networks. The inner ear is comprised of highly specialized cell types with
      identical genomes that originate from a single totipotent zygote. During inner
      ear development specific combinations of transcription factors and epigenetic
      modifiers must function in a coordinated manner to establish and maintain
      cellular identity. These epigenetic regulatory mechanisms contribute to the
      maintenance of distinct chromatin states and cell-type specific gene expression
      patterns. In this review, we highlight emerging paradigms for epigenetic
      modifications related to inner ear development, and how epigenetics may have a
      significant role in hearing loss, protection, and regeneration. 

PMID- 25750611
TI  - Sex hormones affect neurotransmitters and shape the adult female brain during
      hormonal transition periods.
AB  - Sex hormones have been implicated in neurite outgrowth, synaptogenesis, dendritic
      branching, myelination and other important mechanisms of neural plasticity. Here
      we review the evidence from animal experiments and human studies reporting
      interactions between sex hormones and the dominant neurotransmitters, such as
      serotonin, dopamine, GABA and glutamate. We provide an overview of accumulating
      data during physiological and pathological conditions and discuss currently
      conceptualized theories on how sex hormones potentially trigger neuroplasticity
      changes through these four neurochemical systems. Many brain regions have been
      demonstrated to express high densities for estrogen- and progesterone receptors,
      such as the amygdala, the hypothalamus, and the hippocampus. As the hippocampus
      is of particular relevance in the context of mediating structural plasticity in
      the adult brain, we put particular emphasis on what evidence could be gathered
      thus far that links differences in behavior, neurochemical patterns and
      hippocampal structure to a changing hormonal environment. Finally, we discuss how
      physiologically occurring hormonal transition periods in humans can be used to
      model how changes in sex hormones influence functional connectivity,
      neurotransmission and brain structure in vivo. 

PMID- 25750616
TI  - Deletion of KIBRA, protein expressed in kidney and brain, increases filopodial
      like long dendritic spines in neocortical and hippocampal neurons in vivo and in
      vitro.
AB  - Spines are small protrusions arising from dendrites that receive most excitatory
      synaptic input in the brain. Dendritic spines represent dynamic structures that
      undergo activity-dependent adaptations, for example, during synaptic plasticity.
      Alterations of spine morphology, changes of spine type ratios or density have
      consequently been found in paradigms of learning and memory, and accompany many
      neuropsychiatric disorders. Polymorphisms in the gene encoding KIBRA, a protein
      present in kidney and brain, are linked to memory performance and cognition in
      humans and mouse models. Deletion of KIBRA impairs long-term synaptic plasticity
      and postsynaptic receptor recycling but no information is available on the
      morphology of dendritic spines in null-mutant mice. Here, we directly examine the
      role of KIBRA in spinous synapses using knockout mice. Since KIBRA is normally
      highly expressed in neocortex and hippocampus at juvenile age, we analyze synapse
      morphology in intact tissue and in neuronal cultures from these brain regions.
      Quantification of different dendritic spine types in Golgi-impregnated sections
      and in transfected neurons coherently reveal a robust increase of filopodial-like
      long protrusions in the absence of KIBRA. While distribution of pre- and
      postsynaptic marker proteins, overall synapse ultrastructure and density of
      asymmetric contacts were remarkably normal, electron microscopy additionally
      uncovered less perforated synapses and spinules in knockout neurons. Thus, our
      results indicate that KIBRA is involved in the maintenance of normal ratios of
      spinous synapses, and may thus provide a structural correlate of altered
      cognitive functions when this memory-associated molecule is mutated. 

PMID- 25750617
TI  - Thyroid hormone and the developing hypothalamus.
AB  - Thyroid hormone (TH) plays an essential role in normal brain development and
      function. Both TH excess and insufficiency during development lead to structural
      brain abnormalities. Proper TH signaling is dependent on active transport of the
      prohormone thyroxine (T4) across the blood-brain-barrier and into brain cells. In
      the brain T4 undergoes local deiodination into the more active 3,3',5
      triiodothyronine (T3), which binds to nuclear TH receptors (TRs). TRs are already
      expressed during the first trimester of pregnancy, even before the fetal thyroid
      becomes functional. Throughout pregnancy, the fetus is largely dependent on the
      maternal TH supply. Recent studies in mice have shown that normal hypothalamic
      development requires intact TH signaling. In addition, the development of the
      human lateral hypothalamic zone coincides with a strong increase in T3 and TR
      mRNA concentrations in the brain. During this time the fetal hypothalamus already
      shows evidence for TH signaling. Expression of components crucial for central TH
      signaling show a specific developmental timing in the human hypothalamus. A
      coordinated expression of deiodinases in combination with TH transporters
      suggests that TH concentrations are regulated to prevent untimely maturation of
      brain cells. Even though the fetus depends on the maternal TH supply, there is
      evidence suggesting a role for the fetal hypothalamus in the regulation of TH
      serum concentrations. A decrease in expression of proteins involved in TH
      signaling towards the end of pregnancy may indicate a lower fetal TH demand. This
      may be relevant for the thyrotropin (TSH) surge that is usually observed after
      birth, and supports a role for the hypothalamus in the regulation of TH
      concentrations during the fetal period anticipating birth. 

PMID- 25750619
TI  - Why humans might help strangers.
AB  - Humans regularly help strangers, even when interactions are apparently unobserved
      and unlikely to be repeated. Such situations have been simulated in the
      laboratory using anonymous one-shot games (e.g., prisoner's dilemma) where the
      payoff matrices used make helping biologically altruistic. As in real-life,
      participants often cooperate in the lab in these one-shot games with non
      relatives, despite that fact that helping is under negative selection under these
      circumstances. Two broad explanations for such behavior prevail. The "big
      mistake" or "mismatch" theorists argue that behavior is constrained by
      psychological mechanisms that evolved predominantly in the context of repeated
      interactions with known individuals. In contrast, the cultural group selection
      theorists posit that humans have been selected to cooperate in anonymous one-shot
      interactions due to strong between-group competition, which creates
      interdependence among in-group members. We present these two hypotheses before
      discussing alternative routes by which humans could increase their direct fitness
      by cooperating with strangers under natural conditions. In doing so, we explain
      why the standard lab games do not capture real-life in various important aspects.
      First, asymmetries in the cost of perceptual errors regarding the context of the
      interaction (one-shot vs. repeated; anonymous vs. public) might have selected for
      strategies that minimize the chance of making costly behavioral errors. Second,
      helping strangers might be a successful strategy for identifying other
      cooperative individuals in the population, where partner choice can turn
      strangers into interaction partners. Third, in contrast to the assumptions of the
      prisoner's dilemma model, it is possible that benefits of cooperation follow a
      non-linear function of investment. Non-linear benefits result in negative
      frequency dependence even in one-shot games. Finally, in many real-world
      situations individuals are able to parcel investments such that a one-shot
      interaction is turned into a repeated game of many decisions. 

PMID- 25750620
TI  - Comparing different stimulus configurations for population receptive field
      mapping in human fMRI.
AB  - Population receptive field (pRF) mapping is a widely used approach to measuring
      aggregate human visual receptive field properties by recording non-invasive
      signals using functional MRI. Despite growing interest, no study to date has
      systematically investigated the effects of different stimulus configurations on
      pRF estimates from human visual cortex. Here we compared the effects of three
      different stimulus configurations on a model-based approach to pRF estimation:
      size-invariant bars and eccentricity-scaled bars defined in Cartesian coordinates
      and traveling along the cardinal axes, and a novel simultaneous "wedge and ring"
      stimulus defined in polar coordinates, systematically covering polar and
      eccentricity axes. We found that the presence or absence of eccentricity scaling
      had a significant effect on goodness of fit and pRF size estimates. Further,
      variability in pRF size estimates was directly influenced by stimulus
      configuration, particularly for higher visual areas including V5/MT+. Finally, we
      compared eccentricity estimation between phase-encoded and model-based pRF
      approaches. We observed a tendency for more peripheral eccentricity estimates
      using phase-encoded methods, independent of stimulus size. We conclude that both
      eccentricity scaling and polar rather than Cartesian stimulus configuration are
      important considerations for optimal experimental design in pRF mapping. While
      all stimulus configurations produce adequate estimates, simultaneous wedge and
      ring stimulation produced higher fit reliability, with a significant advantage in
      reduced acquisition time. 

PMID- 25750621
TI  - A multimodal approach for determining brain networks by jointly modeling
      functional and structural connectivity.
AB  - Recent innovations in neuroimaging technology have provided opportunities for
      researchers to investigate connectivity in the human brain by examining the
      anatomical circuitry as well as functional relationships between brain regions.
      Existing statistical approaches for connectivity generally examine resting-state
      or task-related functional connectivity (FC) between brain regions or separately
      examine structural linkages. As a means to determine brain networks, we present a
      unified Bayesian framework for analyzing FC utilizing the knowledge of associated
      structural connections, which extends an approach by Patel et al. (2006a) that
      considers only functional data. We introduce an FC measure that rests upon
      assessments of functional coherence between regional brain activity identified
      from functional magnetic resonance imaging (fMRI) data. Our structural
      connectivity (SC) information is drawn from diffusion tensor imaging (DTI) data,
      which is used to quantify probabilities of SC between brain regions. We formulate
      a prior distribution for FC that depends upon the probability of SC between brain
      regions, with this dependence adhering to structural-functional links revealed by
      our fMRI and DTI data. We further characterize the functional hierarchy of
      functionally connected brain regions by defining an ascendancy measure that
      compares the marginal probabilities of elevated activity between regions. In
      addition, we describe topological properties of the network, which is composed of
      connected region pairs, by performing graph theoretic analyses. We demonstrate
      the use of our Bayesian model using fMRI and DTI data from a study of auditory
      processing. We further illustrate the advantages of our method by comparisons to
      methods that only incorporate functional information. 

PMID- 25750618
TI  - Chronic SSRI stimulation of astrocytic 5-HT2B receptors change multiple gene
      expressions/editings and metabolism of glutamate, glucose and glycogen: a
      potential paradigm shift.
AB  - It is firmly believed that the mechanism of action of SSRIs in major depression
      is to inhibit the serotonin transporter, SERT, and increase extracellular
      concentration of serotonin. However, this undisputed observation does not prove
      that SERT inhibition is the mechanism, let alone the only mechanism, by which
      SSRI's exert their therapeutic effects. It has recently been demonstrated that 5
      HT2B receptor stimulation is needed for the antidepressant effect of fluoxetine
      in vivo. The ability of all five currently used SSRIs to stimulate the 5-HT2B
      receptor equipotentially in cultured astrocytes has been known for several years,
      and increasing evidence has shown the importance of astrocytes and astrocyte
      neuronal interactions for neuroplasticity and complex brain activity. This paper
      reviews acute and chronic effects of 5-HT2B receptor stimulation in cultured
      astrocytes and in astrocytes freshly isolated from brains of mice treated with
      fluoxetine for 14 days together with effects of anti-depressant therapy on
      turnover of glutamate and GABA and metabolism of glucose and glycogen. It is
      suggested that these events are causally related to the mechanism of action of
      SSRIs and of interest for development of newer antidepressant drugs. 

PMID- 25750622
TI  - Medical data transformation using rewriting.
AB  - This paper presents a system for declaratively transforming medical subjects'
      data into a common data model representation. Our work is part of the "GAAIN"
      project on Alzheimer's disease data federation across multiple data providers. We
      present a general purpose data transformation system that we have developed by
      leveraging the existing state-of-the-art in data integration and query rewriting.
      In this work we have further extended the current technology with new formalisms
      that facilitate expressing a broader range of data transformation tasks, plus new
      execution methodologies to ensure efficient data transformation for disease
      datasets. 

PMID- 25750623
TI  - Properties and molecular identity of NMDA receptors at synaptic and non-synaptic
      inputs in cerebellar molecular layer interneurons.
AB  - N-methyl-D-aspartate receptors (NMDARs) in cerebellar molecular layer
      interneurons (MLIs) are expressed and activated in unusual ways: at parallel
      fibre (PF) synapses they are only recruited by repetitive stimuli, suggesting an
      extrasynaptic location, whereas their activation by climbing fibre is purely
      mediated by spillover. NMDARs are thought to play an important role in plasticity
      at different levels of the cerebellar circuitry. Evaluation of the location,
      functional properties and physiological roles of NMDARs will be facilitated by
      knowledge of the NMDAR isoforms recruited. Here we show that MLI-NMDARs activated
      by both PF and climbing fibre inputs have similar kinetics and contain GluN2B but
      not GluN2A subunits. On the other hand, no evidence was found of functional
      NMDARs in the axons of MLIs. At the PF-Purkinje cell (PF-PC) synapse, the
      activation of GluN2A-containing NMDARs has been shown to be necessary for the
      induction of long-term depression (LTD). Our results therefore provide a clear
      distinction between the NMDARs located on MLIs and those involved in plasticity
      at PF-PC synapses. 

PMID- 25750624
TI  - Hepatotoxic potential of asarones: in vitro evaluation of hepatotoxicity and
      quantitative determination in herbal products.
AB  - alpha and beta asarones are natural constituents of some aromatic plants,
      especially species of the genus Acorus (Araceae). In addition to reports of
      beneficial properties of asarones, genotoxicity and carcinogenicity are also
      reported. Due to potential toxic effects of beta-asarone, a limit of exposure
      from herbal products of ~2 MUg/kg body weight/day has been set temporarily until
      a full benefit/risk assessment has been carried out by the European Medicines
      Agency. Therefore, it is important to monitor levels of beta-asarone in herbal
      products. In this study, we developed a simple, rapid and validated GC-MS method
      for quantitative determination of asarones and applied it in 20 pediatric herbal
      products after detecting high concentrations of beta-asarone in a product
      suspected to be implicated in hepatotoxicity in a 3 month old infant.
      Furthermore, targeted toxicological effects were further investigated in human
      hepatocytes (THLE-2 cells) by employing various in vitro assays, with the goal of
      elucidating possible mechanisms for the observed toxicity. Results showed that
      some of the products contained as much as 4-25 times greater amounts of beta
      asarone than the recommended levels. In 4 of 10 samples found to contain
      asarones, the presence of asarones could not be linked to the labeled
      ingredients, possibly due to poor quality control. Cell-based investigations in
      THLE-2 cells confirmed the cytotoxicity of beta-asarone (IC50 = 40.0 +/- 2.0
      MUg/mL) which was associated with significant lipid peroxidation and glutathione
      depletion. This observed cytotoxic effect is likely due to induction of oxidative
      stress by asarones. Overall, the results of this study ascertained the usability
      of this GC-MS method for the quantitative determination of asarones from herbal
      products, and shed light on the importance of controlling the concentration of
      potentially toxic asarones in herbal products to safeguard consumer safety,
      especially when the target consumers are young children. Further investigations
      of the toxicity of asarones are warranted. 

PMID- 25750625
TI  - The relevance of theobromine for the beneficial effects of cocoa consumption.
AB  - Cocoa consumption began in America and in the mid sixteenth Century it quickly
      spread to Europe. Beyond being considered a pleasant habit due to its rich sweet
      lingering taste, chocolate was considered a good nutrient and even a medicine.
      Traditionally, health benefits of cocoa have been related with the high content
      of antioxidants of Theobroma cocoa beans. However, the direct psychoactive effect
      due to methylxanthines in cocoa is notable. Theobromine and caffeine, in the
      proportions found in cocoa, are responsible for the liking of the food/beverage.
      These compounds influence in a positive way our moods and our state of alertness.
      Theobromine, which is found in higher amounts than caffeine, seems to be behind
      several effects attributed to cocoa intake. The main mechanisms of action are
      inhibition of phosphodiesterases and blockade of adenosine receptors. Further
      mechanisms are being explored to better understand the health benefits associated
      to theobromine consumption. Unlike what happens in other mammals -pets- included,
      theobromine is safe for humans and has fewer unwanted effects than caffeine.
      Therefore, theobromine deserves attention as one of the most attractive molecules
      in cocoa. 

PMID- 25750626
TI  - Systems pharmacology approaches for optimization of antiangiogenic therapies:
      challenges and opportunities.
AB  - Targeted therapies have become an important therapeutic paradigm for multiple
      malignancies. The rapid development of resistance to these therapies impedes the
      successful management of advanced cancer. Due to the redundancy in angiogenic
      signaling, alternative proangiogenic factors are activated upon treatment with
      anti-VEGF agents. Higher doses of the agents lead to greater stimulation of
      compensatory proangiogenic pathways that limit the therapeutic efficacy of VEGF
      targeted drugs and produce escape mechanisms for tumor. Evidence suggests that
      dose intensity and schedules affect the dynamics of the development of this
      resistance. Thus, an optimal dosing regimen is crucial to maximizing the
      therapeutic benefit of antiangiogenic agents and limiting treatment resistance. A
      systems pharmacology approach using multiscale computational modeling can
      facilitate a mechanistic understanding of these dynamics of angiogenic biomarkers
      and their impacts on tumor reduction and resistance. Herein, we discuss a systems
      pharmacology approach integrating the biology of VEGF-targeted therapy
      resistance, including circulating biomarkers, and pharmacodynamics to enable the
      optimization of antiangiogenic therapy for therapeutic gains. 

PMID- 25750627
TI  - Dissection of the radical reactions linked to fetal hemoglobin reveals enhanced
      pseudoperoxidase activity.
AB  - In the presence of excess hydrogen peroxide (H2O2), ferrous (Fe(+2)) human
      hemoglobin (Hb) (alpha2beta2) undergoes a rapid conversion to a higher oxidation
      ferryl state (Fe(+4)) which rapidly autoreduces back to the ferric form (Fe(+3))
      as H2O2 is consumed in the reaction. In the presence of additional H2O2 the
      ferric state can form both ferryl Hb and an associated protein radical in a
      pseudoperoxidative cycle that results in the loss of radicals and heme
      degradation. We examined whether adult HbA (beta2alpha2) exhibits a different
      pseudoenzymatic activity than fetal Hb (gamma2alpha2) due to the switch of gamma
      to beta subunits. Rapid mixing of the ferric forms of both proteins with excess
      H2O2 resulted in biphasic kinetic time courses that can be assigned to gamma/beta
      and alpha, respectively. Although there was a 1.5 fold increase in the fast
      reacting gamma /beta subunits the slower reacting phases (attributed to alpha
      subunits of both proteins) were essentially the same. However, the rate constant
      for the auto-reduction of ferryl back to ferric for both proteins was found to be
      76% higher for HbF than HbA and in the presence of the mild reducing agent,
      ascorbate there was a 3-fold higher reduction rate in ferryl HbF as opposed to
      ferryl HbA. Using quantitative mass spectrometry in the presence of H2O2 we found
      oxidized gamma/beta Cys93, to be more abundantly present in HbA than HbF, whereas
      higher levels of nitrated beta Tyr35 containing peptides were found in HbA
      samples treated with nitrite. The extraordinary stability of HbF reported here
      may explain the evolutionary advantage this protein may confer onto co-inherited
      hemoglobinopathies and can also be utilized in the engineering of oxidatively
      stable Hb-based oxygen carriers. 

PMID- 25750628
TI  - MicroRNAs in renal fibrosis.
AB  - MicroRNAs (miRNAs) are endogenous short non-coding RNAs that regulate most of
      important cellular processes by inhibiting gene expression through the post
      transcriptional repression of their target mRNAs. In kidneys, miRNAs have been
      associated in renal development, homeostasis, and physiological functions.
      Results from clinical and experimental animal studies demonstrate that miRNAs
      play essential roles in the pathogenesis of various renal diseases. Chronic
      kidney diseases (CKD) is characterized by renal fibrosis. Transforming growth
      factor beta (TGF-beta) is recognized as a major mediator of renal fibrosis
      because it is able to stimulate the accumulation of extracellular matrix (ECM)
      proteins to impair normal kidney function. Recently, emerging evidence
      demonstrate the relationship between TGF-beta signaling and miRNAs expression
      during renal diseases. TGF-beta regulates expression of several microRNAs, such
      as miR-21, miR-192, miR-200, miR-433, and miR-29. MiR-21, miR-192, and miR-433
      which are positively induced by TGF-beta signaling play a pathological role in
      kidney diseases. In contrast, members in both miR-29 and miR-200 families which
      are inhibited by TGF-beta signaling protect kidneys from renal fibrosis by
      suppressing the deposition of ECM and preventing epithelial-to-mesenchymal
      transition, respectively. Clinically, the presence of miRNAs in blood and urine
      has been examined to be early biomarkers for detecting renal diseases. From
      experimental animal studies of CKD, targeting microRNAs also provides evidence
      about therapeutic potential of miRNAs during renal diseases. Now, it comes to the
      stage to examine the exact mechanisms of miRNAs during the initiation and
      progression of renal diseases. Therefore, determining the function of miRNAs in
      renal fibrosis may facilitate the development of both early diagnosis and
      treatment of renal diseases. 

PMID- 25750629
TI  - Endogenous attention modulates attentional and motor interference from
      distractors: evidence from behavioral and electrophysiological results.
AB  - Selective visual attention enhances the processing of relevant stimuli and
      filters out irrelevant stimuli and/or distractors. However, irrelevant
      information is sometimes processed, as demonstrated by the Simon effect (Simon
      and Rudell, 1967). We examined whether fully irrelevant distractors (task and
      target-irrelevant) produce interference (measured as the Simon effect), and
      whether endogenous orienting modulated this interference. Despite being fully
      irrelevant, distractors were attentionally coded (as reflected by the distractor
      related N2pc component), and interfered with the processing of the target
      response (as reflected by the target-related lateralized readiness potential
      component). Distractors' attentional capture depended on endogenous attention,
      and their interference with target responses was modulated by both endogenous
      attention and distractor location repetition. These results demonstrate both
      endogenous attentional and motor modulations over the Simon effect produced by
      fully irrelevant distractors. 

PMID- 25750630
TI  - Unifying treatments for depression: an application of the Free Energy Principle.
AB  - Major Depressive Disorder is a debilitating and increasingly prevalent
      psychiatric condition (Compton et al., 2006; Andersen et al., 2011). At present,
      its primary treatments are antidepressant medications and psychotherapy.
      Curiously, although the pharmacological effects of antidepressants manifest
      within hours, remission of clinical symptoms takes a number of weeks-if at all.
      Independently, support has grown for an idea-proposed as early as Helmholtz (von
      Helmholtz, 1924)-that the brain is a prediction machine, holding generative
      models for the purpose of inferring causes of sensory information (Dayan et al.,
      1995; Rao and Ballard, 1999; Knill and Pouget, 2004; Friston et al., 2006;
      Friston, 2010). If the brain does indeed represent a collection of beliefs about
      the causal structure of the world, then the depressed phenotype may emerge from a
      collection of depressive beliefs. These beliefs are modified gradually through
      successive combinations of expectations with observations. As a result,
      phenotypic remission ought to take some time as the brain's relevant statistical
      structures become less pessimistic. 

PMID- 25750632
TI  - Challenges in determining whether creativity and mental illness are associated.

PMID- 25750631
TI  - Tactile input and empathy modulate the perception of ambiguous biological motion.
AB  - Evidence has shown that task-irrelevant auditory cues can bias perceptual
      decisions regarding directional information associated with biological motion, as
      indicated in perceptual tasks using point-light walkers (PLWs) (Brooks et al.,
      2007). In the current study, we extended the investigation of cross-modal
      influences to the tactile domain by asking how tactile input resolves perceptual
      ambiguity in visual apparent motion, and how empathy plays a role in this cross
      modal interaction. In Experiment 1, we simulated the tactile feedback on the
      observers' fingertips when the (upright or inverted) PLWs (comprised of either
      all red or all green dots) were walking (leftwards or rightwards). The temporal
      periods between tactile events and critical visual events (the PLW's feet hitting
      the ground) were manipulated so that the tap could lead, synchronize, or lag the
      visual foot-hitting-ground event. We found that the temporal structures between
      tactile (feedback) and visual (hitting) events systematically biases the
      directional perception for upright PLWs, making either leftwards or rightwards
      more dominant. However, this effect was absent for inverted PLWs. In Experiment
      2, we examined how empathy modulates cross-modal capture. Instead of giving
      tactile feedback on participants' fingertips, we gave taps on their ankles and
      presented the PLWs with motion directions of approaching (facing toward
      observer)/receding (facing away from observer) to resemble normal walking
      postures. With the same temporal structure, we found that individuals with higher
      empathy were more subject to perceptual bias in the presence of tactile feedback.
      Taken together, our findings showed that task-irrelevant tactile input can
      resolve the otherwise ambiguous perception of the direction of biological motion,
      and this cross-modal bias was mediated by higher level social-cognitive factors,
      including empathy. 

PMID- 25750633
TI  - Basic and supplementary sensory feedback in handwriting.
AB  - The mastering of handwriting is so essential in our society that it is important
      to try to find new methods for facilitating its learning and rehabilitation. The
      ability to control the graphic movements clearly impacts on the quality of the
      writing. This control allows both the programming of letter formation before
      movement execution and the online adjustments during execution, thanks to diverse
      sensory feedback (FB). New technologies improve existing techniques or enable new
      methods to supply the writer with real-time computer-assisted FB. The
      possibilities are numerous and various. Therefore, two main questions arise: (1)
      What aspect of the movement is concerned and (2) How can we best inform the
      writer to help them correct their handwriting? In a first step, we report studies
      on FB naturally used by the writer. The purpose is to determine which information
      is carried by each sensory modality, how it is used in handwriting control and
      how this control changes with practice and learning. In a second step, we report
      studies on supplementary FB provided to the writer to help them to better control
      and learn how to write. We suggest that, depending on their contents, certain
      sensory modalities will be more appropriate than others to assist handwriting
      motor control. We emphasize particularly the relevance of auditory modality as
      online supplementary FB on handwriting movements. Using real-time supplementary
      FB to assist in the handwriting process is probably destined for a brilliant
      future with the growing availability and rapid development of tablets. 

PMID- 25750635
TI  - Salicylate-induced hearing loss and gap detection deficits in rats.
AB  - To test the "tinnitus gap-filling" hypothesis in an animal psychoacoustic
      paradigm, rats were tested using a go/no-go operant gap detection task in which
      silent intervals of various durations were embedded within a continuous noise.
      Gap detection thresholds were measured before and after treatment with a dose of
      sodium salicylate (200 mg/kg) that reliably induces tinnitus in rats. Noise-burst
      detection thresholds were also measured to document the amount of hearing loss
      and aid in interpreting the gap detection results. As in the previous human
      psychophysical experiments, salicylate had little or no effect on gap thresholds
      measured in broadband noise presented at high-stimulus levels (30-60 dB SPL); gap
      detection thresholds were always 10 ms or less. Salicylate also did not affect
      gap thresholds presented in narrowband noise at 60 dB SPL. Therefore, rats
      treated with a dose of salicylate that reliably induces tinnitus have no
      difficulty detecting silent gaps as long as the noise in which they are embedded
      is clearly audible. 

PMID- 25750634
TI  - Pharmacogenetics of antipsychotic-induced movement disorders as a resource for
      better understanding Parkinson's disease modifier genes.
AB  - Antipsychotic-induced movement disorders are major side effects of antipsychotic
      drugs among schizophrenia patients, and include antipsychotic-induced
      parkinsonism (AIP) and tardive dyskinesia (TD). Substantial pharmacogenetic work
      has been done in this field, and several susceptibility variants have been
      suggested. In this paper, the genetics of antipsychotic-induced movement
      disorders is considered in a broader context. We hypothesize that genetic
      variants that are risk factors for AIP and TD may provide insights into the
      pathophysiology of motor symptoms in Parkinson's disease (PD). Since loss of
      dopaminergic stimulation (albeit pharmacological in AIP and degenerative in PD)
      is shared by the two clinical entities, genes associated with susceptibility to
      AIP may be modifier genes that influence clinical expression of PD motor sub
      phenotypes, such as age at onset, disease severity, or rate of progression. This
      is due to their possible functional influence on compensatory mechanisms for
      striatal dopamine loss. Better compensatory potential might be beneficial at the
      early and later stages of the PD course. AIP vulnerability variants could also be
      related to latent impairment in the nigrostriatal pathway, affecting its
      functionality, and leading to subclinical dopaminergic deficits in the striatum.
      Susceptibility of PD patients to early development of l-DOPA induced dyskinesia
      (LID) is an additional relevant sub-phenotype. LID might share a common genetic
      background with TD, with which it shares clinical features. Genetic risk variants
      may predispose to both phenotypes, exerting a pleiotropic effect. According to
      this hypothesis, elucidating the genetics of antipsychotic-induced movement
      disorders may advance our understanding of multiple aspects of PD and it clinical
      course, rendering this a potentially rewarding field of study. 

PMID- 25750636
TI  - Promoter methylation status of Ras-association domain family members in
      pheochromocytoma.
AB  - Pheochromocytomas (PCCs) are rare neuroendocrine tumors that arise from the
      medulla of the adrenal gland or the sympathetic ganglia and are characterized by
      the secretion of catecholamines. In 30-40% of patients, PCCs are genetically
      determined by susceptibility genes as various as RET, VHL, and NF1. We have
      analyzed the Ras-association domain family members (RASSFs) in PCCs regarding
      their inactivating promoter hypermethylation status. Previously, we reported a
      promoter methylation in PCC for the first family member RASSF1A. Promoter
      hypermethylation of CpG islands leads to the silencing of the according
      transcript and is a common mechanism for inactivation of tumor suppressors. In
      this study, we observed inactivating DNA modifications for the RASSF members
      RASSF2, RASSF5A, RASSF9, and RASSF10, but not for the members RASSF3, RASSF4,
      RASSF5C, RASSF6, RASSF7, and RASSF8. The degree of promoter methylation was 19%
      for RASSF2, 67% for RASSF5A, 18% for RASSF9, and 74% for RASSF10. Interestingly,
      the degree of hypermethylation for RASSF10 in hereditary PCCs was 89 vs. 60% in
      sporadic PCCs. A similar but less dramatic effect was observed in RASSF5A and
      RASSF9. Including all RASSF members, we found that of 25 PCCs, 92% show promoter
      methylation in at least in one RASSF member. In 75% of the hereditary PCC
      samples, we found two or more methylated RASSF promoters, whereas in sporadic
      PCCs only 46% were observed. In summary, we could show that in PCC several RASSF
      members are strongly hypermethylated in their promoter regions and methylation of
      more than one RASSF member occurs in the majority of PCCs. This adds the
      inactivation of genes of the RASSF tumor suppressor family to the already known
      deregulated genes of PCC. 

PMID- 25750637
TI  - Heavy metal whole-cell biosensors using eukaryotic microorganisms: an updated
      critical review.
AB  - This review analyzes the advantages and disadvantages of using eukaryotic
      microorganisms to design whole-cell biosensors (WCBs) for monitoring
      environmental heavy metal pollution in soil or aquatic habitats. Basic
      considerations for designing a eukaryotic WCB are also shown. A comparative
      analysis of the promoter genes used to design WCBs is carried out, and the
      sensitivity and reproducibility of the main reporter genes used is also reviewed.
      Three main eukaryotic taxonomic groups are considered: yeasts, microalgae, and
      ciliated protozoa. Models that have been widely analyzed as potential WCBs are
      the Saccharomyces cerevisiae model among yeasts, the Tetrahymena thermophila
      model for ciliates and Chlamydomonas model for microalgae. The advantages and
      disadvantages of each microbial group are discussed, and a ranking of sensitivity
      to the same type of metal pollutant from reported eukaryotic WCBs is also shown.
      General conclusions and possible future developments of eukaryotic WCBs are
      reported. 

PMID- 25750639
TI  - Characterization of a single mutation in TraQ in a strain of Escherichia coli
      partially resistant to Qbeta infection.
AB  - Bacteria and virulent bacteriophages are in a prey-predator relationship.
      Experimental models under simplified conditions with the presence of bacteria and
      bacteriophages have been used to elucidate the mechanisms that have enabled both
      prey and predator to coexist over long periods. In experimental coevolution
      conducted with Escherichia coli and the virulent RNA bacteriophage Qbeta in
      serial transfer, both coexisted for at least for 54 days, during which time they
      continued to change genetically and phenotypically. By day 16, an E. coli strain
      partially resistant to Qbeta appeared and caused an approximately 10(4)-fold
      decrease in Qbeta amplification. Whole-genome analysis of this strain suggested
      that a single mutation in TraQ was responsible for the partially resistant
      phenotype. TraQ interacts with propilin, encoded by the traA gene and a precursor
      of pilin, which is a component of the F pilus. The present study was performed to
      elucidate the mechanism underlying the coexistence of E. coli and Qbeta by
      investigating how a mutation in TraQ altered the physiological state of E. coli,
      and thus the amplification of Qbeta. Overexpression of wild-type TraQ in the
      partially resistant E. coli strain resulted in recovery of both TraA protein
      content, including propilin and pilin, and Qbeta amplification to levels
      comparable to those observed in the susceptible strain. Intriguingly,
      overexpression of the mutant TraQ in the partially resistant strains also
      increased the levels of TraA protein and Qbeta amplification, but these increases
      were smaller than those observed in the wild-type strain or the partially
      resistant strain expressing wild-type TraQ. The results of this study represent
      an example of how E. coli can become partially resistant to RNA bacteriophage
      infection via changes in a protein involved in maturation of a receptor rather
      than in the receptor itself and of how E. coli can stably coexist with virulent
      RNA bacteriophages. 

PMID- 25750638
TI  - Pre-symptomatic diagnosis and treatment of filovirus diseases.
AB  - Filoviruses are virulent human pathogens which cause severe illness with high
      case fatality rates and for which there are no available FDA-approved vaccines or
      therapeutics. Diagnostic tools including antibody- and molecular-based assays,
      mass spectrometry, and next-generation sequencing are continually under
      development. Assays using the polymerase chain reaction (PCR) have become the
      mainstay for the detection of filoviruses in outbreak settings. In many cases,
      real-time reverse transcriptase-PCR allows for the detection of filoviruses to be
      carried out with minimal manipulation and equipment and can provide results in
      less than 2 h. In cases of novel, highly diverse filoviruses, random-primed
      pyrosequencing approaches have proved useful. Ideally, diagnostic tests would
      allow for diagnosis of filovirus infection as early as possible after infection,
      either before symptoms begin, in the event of a known exposure or epidemiologic
      outbreak, or post-symptomatically. If tests could provide an early definitive
      diagnosis, then this information may be used to inform the choice of possible
      therapeutics. Several exciting new candidate therapeutics have been described
      recently; molecules that have therapeutic activity when administered to animal
      models of infection several days post-exposure, once signs of disease have begun.
      The latest data for candidate nucleoside analogs, small interfering RNA (siRNA)
      molecules, phosphorodiamidate (PMO) molecules, as well as antibody and blood
      product therapeutics and therapeutic vaccines are discussed. For filovirus
      researchers and government agencies interested in making treatments available for
      a nation's defense as well as its general public, having the right diagnostic
      tools to identify filovirus infections, as well as a panel of available
      therapeutics for treatment when needed, is a high priority. Additional research
      in both areas is required for ultimate success, but significant progress is being
      made to reach these goals. 

PMID- 25750640
TI  - Elevated atmospheric CO2 levels affect community structure of rice root
      associated bacteria.
AB  - A number of studies have shown that elevated atmospheric CO2 ([CO2]) affects rice
      yields and grain quality. However, the responses of root-associated bacteria to
      [CO2] elevation have not been characterized in a large-scale field study. We
      conducted a free-air CO2 enrichment (FACE) experiment (ambient + 200 MUmol.mol(
      1)) using three rice cultivars (Akita 63, Takanari, and Koshihikari) and two
      experimental lines of Koshihikari [chromosome segment substitution and near
      isogenic lines (NILs)] to determine the effects of [CO2] elevation on the
      community structure of rice root-associated bacteria. Microbial DNA was extracted
      from rice roots at the panicle formation stage and analyzed by pyrosequencing the
      bacterial 16S rRNA gene to characterize the members of the bacterial community.
      Principal coordinate analysis of a weighted UniFrac distance matrix revealed that
      the community structure was clearly affected by elevated [CO2]. The predominant
      community members at class level were Alpha-, Beta-, and Gamma-proteobacteria in
      the control (ambient) and FACE plots. The relative abundance of Methylocystaceae,
      the major methane-oxidizing bacteria in rice roots, tended to decrease with
      increasing [CO2] levels. Quantitative PCR revealed a decreased copy number of the
      methane monooxygenase (pmoA) gene and increased methyl coenzyme M reductase
      (mcrA) in elevated [CO2]. These results suggest elevated [CO2] suppresses methane
      oxidation and promotes methanogenesis in rice roots; this process affects the
      carbon cycle in rice paddy fields. 

PMID- 25750641
TI  - Sudden infant death syndrome and the genetics of inflammation.
AB  - Several studies report signs of slight infection prior to death in cases of
      sudden infant death syndrome (SIDS). Based on this, a hypothesis of an altered
      immunological homeostasis has been postulated. The cytokines are important
      cellular mediators that are crucial for infant health by regulating cell activity
      during the inflammatory process. The pro-inflammatory cytokines favor
      inflammation; the most important of these are IL-1alpha, IL-1beta, IL-6, IL-8, IL
      12, IL-18, TNF-alpha, and IFN-gamma. These cytokines are controlled by the anti
      inflammatory cytokines. This is accomplished by reducing the pro-inflammatory
      cytokine production, and thus counteracts their biological effect. The major anti
      inflammatory cytokines are interleukin-1 receptor antagonist (IL-1ra), IL-4, IL
      10, IL-11, and IL-13. The last decade there has been focused on genetic studies
      within genes that are important for the immune system, for SIDS with a special
      interest of the genes encoding the cytokines. This is because the cytokine genes
      are considered to be the genes most likely to explain the vulnerability to
      infection, and several studies have investigated these genes in an attempt to
      uncover associations between SIDS and different genetic variants. So far, the
      genes encoding IL-1, IL-6, IL-10, and TNF-alpha are the most investigated within
      SIDS research, and several studies indicate associations between specific
      variants of these genes and SIDS. Taken together, this may indicate that in at
      least a subset of SIDS predisposing genetic variants of the immune genes are
      involved. However, the immune system and the cytokine network are complex, and
      more studies are needed in order to better understand the interplay between
      different genetic variations and how this may contribute to an unfavorable
      immunological response. 

PMID- 25750643
TI  - Metabolic responses to sulfur dioxide in grapevine (Vitis vinifera L.):
      photosynthetic tissues and berries.
AB  - Research on sulfur metabolism in plants has historically been undertaken within
      the context of industrial pollution. Resolution of the problem of sulfur
      pollution has led to sulfur deficiency in many soils. Key questions remain
      concerning how different plant organs deal with reactive and potentially toxic
      sulfur metabolites. In this review, we discuss sulfur dioxide/sulfite
      assimilation in grape berries in relation to gene expression and quality traits,
      features that remain significant to the food industry. We consider the intrinsic
      metabolism of sulfite and its consequences for fruit biology and postharvest
      physiology, comparing the different responses in fruit and leaves. We also
      highlight inconsistencies in what is considered the "ambient" environmental or
      industrial exposures to SO2. We discuss these findings in relation to the
      persistent threat to the table grape industry that intergovernmental agencies
      will revoke the industry's exemption to the worldwide ban on the use of SO2 for
      preservation of fresh foods. Transcriptome profiling studies on fruit suggest
      that added value may accrue from effects of SO2 fumigation on the expression of
      genes encoding components involved in processes that underpin traits related to
      customer satisfaction, particularly in table grapes, where SO2 fumigation may
      extend for several months. 

PMID- 25750642
TI  - Are Platelets Cells? And if Yes, are They Immune Cells?
AB  - Small fragments circulating in the blood were formally identified by the end of
      the nineteenth century, and it was suggested that they assisted coagulation via
      interactions with vessel endothelia. Wright, at the beginning of the twentieth
      century, identified their bone-marrow origin. For long, platelets have been
      considered sticky assistants of hemostasis and pollutants of blood or tissue
      samples; they were just cell fragments. As such, however, they were acknowledged
      as immunizing (to specific HPA and HLA markers): the platelet's dark face. The
      enlightened face showed that besides hemostasis, platelets contained factors
      involved in healing. As early as 1930s, platelets entered the arsenal of
      medicines were transfused, and were soon manipulated to become a kind of glue to
      repair damaged tissues. Some gladly categorized platelets as cells but they were
      certainly not fully licensed as such for cell physiologists. Actually, platelets
      possess almost every characteristic of cells, apart from being capable of
      organizing their genes: they have neither a nucleus nor genes. This view
      prevailed until it became evident that platelets play a role in homeostasis and
      interact with cells other than with vascular endothelial cells; then began the
      era of physiological and also pathological inflammation. Platelets have now
      entered the field of immunity as inflammatory cells. Does assistance to immune
      cells itself suffice to license a cell as an "immune cell"? Platelets prove
      capable of sensing different types of signals and organizing an appropriate
      response. Many cells can do that. However, platelets can use a complete
      signalosome (apart from the last transcription step, though it is likely that
      this step can be circumvented by retrotranscribing RNA messages). The question
      has also arisen as to whether platelets can present antigen via their abundantly
      expressed MHC class I molecules. In combination, these properties argue in favor
      of allowing platelets the title of immune cells. 

PMID- 25750644
TI  - Linking salinity stress tolerance with tissue-specific Na(+) sequestration in
      wheat roots.
AB  - Salinity stress tolerance is a physiologically complex trait that is conferred by
      the large array of interacting mechanisms. Among these, vacuolar Na(+)
      sequestration has always been considered as one of the key components
      differentiating between sensitive and tolerant species and genotypes. However,
      vacuolar Na(+) sequestration has been rarely considered in the context of the
      tissue-specific expression and regulation of appropriate transporters
      contributing to Na(+) removal from the cytosol. In this work, six bread wheat
      varieties contrasting in their salinity tolerance (three tolerant and three
      sensitive) were used to understand the essentiality of vacuolar Na(+)
      sequestration between functionally different root tissues, and link it with the
      overall salinity stress tolerance in this species. Roots of 4-day old wheat
      seedlings were treated with 100 mM NaCl for 3 days, and then Na(+) distribution
      between cytosol and vacuole was quantified by CoroNa Green fluorescent dye
      imaging. Our major observations were as follows: (1) salinity stress tolerance
      correlated positively with vacuolar Na(+) sequestration ability in the mature
      root zone but not in the root apex; (2) contrary to expectations, cytosolic Na(+)
      levels in root meristem were significantly higher in salt tolerant than sensitive
      group, while vacuolar Na(+) levels showed an opposite trend. These results are
      interpreted as meristem cells playing a role of the "salt sensor;" (3) no
      significant difference in the vacuolar Na(+) sequestration ability was found
      between sensitive and tolerant groups in either transition or elongation zones;
      (4) the overall Na(+) accumulation was highest in the elongation zone, suggesting
      its role in osmotic adjustment and turgor maintenance required to drive root
      expansion growth. Overall, the reported results suggest high tissue-specificity
      of Na(+) uptake, signaling, and sequestration in wheat roots. The implications of
      these findings for plant breeding for salinity stress tolerance are discussed. 

PMID- 25750645
TI  - Arabidopsis flower specific defense gene expression patterns affect resistance to
      pathogens.
AB  - We investigated whether the Arabidopsis flower evolved protective measures to
      increase reproductive success. Firstly, analyses of available transcriptome data
      show that the most highly expressed transcripts in the closed sepal (stage 12)
      are enriched in genes with roles in responses to chemical stimuli and cellular
      metabolic processes. At stage 15, there is enrichment in transcripts with a role
      in responses to biotic stimuli. Comparative analyses between the sepal and petal
      in the open flower mark an over-representation of transcripts with a role in
      responses to stress and catalytic activity. Secondly, the content of the biotic
      defense-associated phytohormone salicylic acid (SA) in sepals and petals is
      significantly higher than in leaves. To understand whether the high levels of
      stress responsive transcripts and the higher SA content affect defense, wild-type
      plants (Col-0) and transgenic plants defective in SA accumulation (nahG) were
      challenged with the biotrophic fungus Golovinomyces cichoracearum, the causal
      agent of powdery mildew, and the necrotrophic fungus Botrytis cinerea. NahG
      leaves were more sensitive than those of Col-0, suggesting that in leaves SA has
      a role in the defense against biotrophs. In contrast, sepals and petals of both
      genotypes were resistant to G. cichoracearum, indicating that in the flower,
      resistance to the biotrophic pathogen is not critically dependent on SA, but
      likely dependent on the up-regulation of stress-responsive genes. Since sepals
      and petals of both genotypes are equally susceptible to B. cinerea, we conclude
      that neither stress-response genes nor increased SA accumulation offers
      protection against the necrotrophic pathogen. These results are interpreted in
      the light of the distinctive role of the flower and we propose that in the early
      stages, the sepal may act as a chemical defense barrier of the developing
      reproductive structures against biotrophic pathogens. 

PMID- 25750646
TI  - A little bit of sex matters for genome evolution in asexual plants.
AB  - Genome evolution in asexual organisms is theoretically expected to be shaped by
      various factors: first, hybrid origin, and polyploidy confer a genomic
      constitution of highly heterozygous genotypes with multiple copies of genes;
      second, asexuality confers a lack of recombination and variation in populations,
      which reduces the efficiency of selection against deleterious mutations; hence,
      the accumulation of mutations and a gradual increase in mutational load (Muller's
      ratchet) would lead to rapid extinction of asexual lineages; third, allelic
      sequence divergence is expected to result in rapid divergence of lineages
      (Meselson effect). Recent transcriptome studies on the asexual polyploid complex
      Ranunculus auricomus using single-nucleotide polymorphisms confirmed neutral
      allelic sequence divergence within a short time frame, but rejected a hypothesis
      of a genome-wide accumulation of mutations in asexuals compared to sexuals,
      except for a few genes related to reproductive development. We discuss a general
      model that the observed incidence of facultative sexuality in plants may unmask
      deleterious mutations with partial dominance and expose them efficiently to
      purging selection. A little bit of sex may help to avoid genomic decay and
      extinction. 

PMID- 25750647
TI  - Uptake of carbamazepine by rhizomes and endophytic bacteria of Phragmites
      australis.
AB  - Carbamazepine is an antiepileptic and mood-stabilizing drug which is used widely
      in Europe and North America. In the environment, it is found as a persistent and
      recalcitrant contaminant, being one of the most prominent hazardous
      pharmaceuticals and personal care products in effluents of wastewater treatment
      plants. Phragmites australis is one of the species with both, the highest
      potential of detoxification and phytoremediation. It has been used successfully
      in the treatment of industrial and municipal wastewater. Recently, the
      identification of endophytic microorganisms from different plant species growing
      in contaminated sites has provided a list of candidates which could be used as
      bio-inoculants for bioremediation of difficult compounds. In this study,
      Phragmites australis plants were exposed to 5 mg/L of carbamazepine. After 9 days
      the plants had removed 90% of the initial concentration. Endophytic bacteria were
      isolated from these plants and further characterized. Phylogenetic analysis based
      on 16S rDNA sequencing revealed that the majority of these isolates belong to
      three groups: Proteobacteria, Actinobacteria, and Bacteroidetes. Carbamazepine
      uptake and plant growth promoting (PGP) traits were analyzed among the isolates.
      Ninety percent of the isolates produce indole acetic acid (IAA) and all of them
      possess at least one of the PGP traits tested. One isolate identified as
      Chryseobacterium taeanense combines good carbamazepine uptake and all of the PGP
      traits. Rhizobium daejeonense can remove carbamazepine and produces 23 MUg/mL of
      IAA. Diaphorobacter nitroreducens and Achromobacter mucicolens are suitable for
      carbamazepine removal while both, Pseudomonas veronii and Pseudomonas lini show
      high siderophore production and phosphate solubilization. Alone or in
      combination, these isolates might be applied as inoculates in constructed
      wetlands in order to enhance the phytoremediation of carbamazepine during
      wastewater treatment. 

PMID- 25750648
TI  - Fructan biosynthesis and degradation as part of plant metabolism controlling
      sugar fluxes during durum wheat kernel maturation.
AB  - Wheat kernels contain fructans, fructose based oligosaccharides with prebiotic
      properties, in levels between 2 and 35 weight % depending on the developmental
      stage of the kernel. To improve knowledge on the metabolic pathways leading to
      fructan storage and degradation, carbohydrate fluxes occurring during durum wheat
      kernel development were analyzed. Kernels were collected at various developmental
      stages and quali-quantitative analysis of carbohydrates (mono- and di
      saccharides, fructans, starch) was performed, alongside analysis of the
      activities and gene expression of the enzymes involved in their biosynthesis and
      hydrolysis. High resolution HPAEC-PAD of fructan contained in durum wheat kernels
      revealed that fructan content is higher at the beginning of kernel development,
      when fructans with higher DP, such as bifurcose and 1,1-nystose, were mainly
      found. The changes in fructan pool observed during kernel maturation might be
      part of the signaling pathways influencing carbohydrate metabolism and storage in
      wheat kernels during development. During the first developmental stages fructan
      accumulation may contribute to make kernels more effective Suc sinks and to
      participate in osmotic regulation while the observed decrease in their content
      may mark the transition to later developmental stages, transition that is also
      orchestrated by changes in redox balance. 

PMID- 25750649
TI  - Differential response to sulfur nutrition of two common bean genotypes differing
      in storage protein composition.
AB  - It has been hypothesized that the relatively low concentration of sulfur amino
      acids in legume seeds might be an ecological adaptation to nutrient poor,
      marginal soils. SARC1 and SMARC1N-PN1 are genetically related lines of common
      bean (dry bean, Phaseolus vulgaris) differing in seed storage protein
      composition. In SMARC1N-PN1, the lack of phaseolin and major lectins is
      compensated by increased levels of sulfur-rich proteins, resulting in an enhanced
      concentration of cysteine and methionine, mostly at the expense of the abundant
      non-protein amino acid, S-methylcysteine. To identify potential effects
      associated with an increased concentration of sulfur amino acids in the protein
      pool, the response of the two genotypes to low and high sulfur nutrition was
      evaluated under controlled conditions. Seed yield was increased by the high
      sulfate treatment in SMARC1N-PN1. The seed concentrations of sulfur, sulfate, and
      S-methylcysteine were altered by the sulfur treatment in both genotypes. The
      concentration of total cysteine and extractible globulins was increased
      specifically in SMARC1N-PN1. Proteomic analysis identified arcelin-like protein
      4, lipoxygenase-3, albumin-2, and alpha amylase inhibitor beta chain as having
      increased levels under high sulfur conditions. Lipoxygenase-3 accumulation was
      sensitive to sulfur nutrition only in SMARC1N-PN1. Under field conditions, both
      SARC1 and SMARC1N-PN1 exhibited a slight increase in yield in response to sulfur
      treatment, typical for common bean. 

PMID- 25750650
TI  - Eucalyptus obliqua seedling growth in organic vs. mineral soil horizons.
AB  - Eucalyptus obliqua, the most widespread timber tree in Tasmania, is a pioneer
      after fire which can eliminate the organic layer of forest soil, exposing the
      underlying mineral soil. We compared seedling growth, mycorrhiza formation, and
      mineral nutrient limitation in organic layer vs. mineral soil. We grew E. obliqua
      seedlings separately in pots of organic layer and mineral soil in a glasshouse.
      Additional treatments of organic soil only, involved fully crossed methyl-bromide
      fumigation and fertilization. Fertilization comprised chelated iron for 121 days
      after transplant (DAT) followed by soluble phosphorus. At 357 DAT, whole plant
      dry weight was three times greater in ambient organic than in mineral soil. In
      organic soil, fumigation halved ectomycorrhiza abundance and reduced seedling
      growth at 149 DAT, but by 357 DAT when negative effects of fumigation on seedling
      growth had disappeared, neither fumigation nor fertilization affected mycorrhiza
      abundance. Iron fertilization diminished seedling growth, but subsequent
      phosphorus fertilization improved it. E. obliqua seedlings grow much better in
      organic layer soil than in mineral soil, although phosphorus remains limiting.
      The prevalent forestry practice of burning to mineral soil after timber harvest
      exposes a poor growth medium likely only partially compensated by fire-induced
      mineral soil alterations. 

PMID- 25750651
TI  - CoVennTree: a new method for the comparative analysis of large datasets.
AB  - The visualization of massive datasets, such as those resulting from comparative
      metatranscriptome analyses or the analysis of microbial population structures
      using ribosomal RNA sequences, is a challenging task. We developed a new method
      called CoVennTree (Comparative weighted Venn Tree) that simultaneously compares
      up to three multifarious datasets by aggregating and propagating information from
      the bottom to the top level and produces a graphical output in Cytoscape. With
      the introduction of weighted Venn structures, the contents and relationships of
      various datasets can be correlated and simultaneously aggregated without losing
      information. We demonstrate the suitability of this approach using a dataset of
      16S rDNA sequences obtained from microbial populations at three different depths
      of the Gulf of Aqaba in the Red Sea. CoVennTree has been integrated into the
      Galaxy ToolShed and can be directly downloaded and integrated into the user
      instance. 

PMID- 25750652
TI  - Genomic selection needs to be carefully assessed to meet specific requirements in
      livestock breeding programs.
AB  - Genomic selection is a promising development in agriculture, aiming improved
      production by exploiting molecular genetic markers to design novel breeding
      programs and to develop new markers-based models for genetic evaluation. It opens
      opportunities for research, as novel algorithms and lab methodologies are
      developed. Genomic selection can be applied in many breeds and species. Further
      research on the implementation of genomic selection (GS) in breeding programs is
      highly desirable not only for the common good, but also the private sector
      (breeding companies). It has been projected that this approach will improve
      selection routines, especially in species with long reproduction cycles, late or
      sex-limited or expensive trait recording and for complex traits. The task of
      integrating GS into existing breeding programs is, however, not straightforward.
      Despite successful integration into breeding programs for dairy cattle, it has
      yet to be shown how much emphasis can be given to the genomic information and how
      much additional phenotypic information is needed from new selection candidates.
      Genomic selection is already part of future planning in many breeding companies
      of pigs and beef cattle among others, but further research is needed to fully
      estimate how effective the use of genomic information will be for the prediction
      of the performance of future breeding stock. Genomic prediction of production in
      crossbreeding and across-breed schemes, costs and choice of individuals for
      genotyping are reasons for a reluctance to fully rely on genomic information for
      selection decisions. Breeding objectives are highly dependent on the industry and
      the additional gain when using genomic information has to be considered
      carefully. This review synthesizes some of the suggested approaches in selected
      livestock species including cattle, pig, chicken, and fish. It outlines tasks to
      help understanding possible consequences when applying genomic information in
      breeding scenarios. 

PMID- 25750653
TI  - Effects of mountain formation and uplift on biological diversity.

PMID- 25750655
TI  - The influence of self-compassion on emotional well-being among early and older
      adolescent males and females.
AB  - Self-compassion has been associated with well-being in adult samples, but has
      rarely been assessed in adolescents. In this study, 90 students ages 11-18
      completed an online survey assessing self-compassion, life satisfaction,
      perceived stress and positive and negative affect. Findings indicated that older
      female adolescents had lower self-compassion than either older male adolescents
      or early adolescents of either gender, and self-compassion was associated
      significantly with all dimensions of emotional well-being with the exception of
      positive affect. Additionally, phase of adolescence, but not gender, was found to
      moderate the relationship between self-compassion and dimensions of well-being;
      for older adolescents, the inverse relationship between self-compassion and
      negative affect was stronger. Lastly, the influence of the various components of
      self-compassion was investigated and discussed.

PMID- 25750654
TI  - The altered fate of aging satellite cells is determined by signaling and
      epigenetic changes.
AB  - Skeletal muscle is a striated tissue composed of multinucleated fibers that
      contract under the control of the somatic nervous system to direct movement. The
      stem cells of skeletal muscle, known as satellite cells, are responsible for
      muscle fiber growth, turnover, and regeneration. Satellite cells are activated
      and proliferate in response to stimuli, and simplistically, have two main fates
      to repopulate the satellite cell niche, or differentiate to regenerate or repair
      muscle fibers. However, the ability to regenerate muscle and replace lost
      myofibers declines with age. This loss of function may be a result of extrinsic
      changes in the niche, such as alterations in signaling or modifications to the
      extracellular matrix. However, intrinsic epigenetic changes within satellite
      cells may also affect cell fate and cause a decline in regenerative capacity.
      This review will describe the mechanisms that regulate cell fate decisions in
      adult skeletal muscle, and how changes during aging affect muscle fiber turnover
      and regeneration. 

PMID- 25750656
TI  - Infants and young children feeding practices and nutritional status in two
      districts of Zambia.
AB  - BACKGROUND: Appropriate feeding is important in improving nutrition and child
      survival. Documentation of knowledge of caregiver on infant feeding is scanty in
      Zambia. The aim of this study was to describe feeding practices and nutritional
      status among infants and young children (IYC) in two districts in Zambia: Kafue
      and Mazabuka. METHODS: A cross-sectional study was conducted between January and
      March 2006 using both quantitative and qualitative methods. A questionnaire was
      administered to caregiver of children aged under24 months. Lengths and weights of
      all children were measured. Focused group discussions were conducted in selected
      communities to assess parents or guardian knowledge, attitude and practice
      related to infant feeding. RESULTS: A total of 634 caregivers (361 from Kafue and
      273 from Mazabuka) participated in the study. About 311/618 (54.0%) of the
      caregiver knew the definition and recommended duration of exclusive breastfeeding
      (EBF) and when to introduce complementary feeds. Two hundred and fifty-one
      (81.2%) out of 310 respondents had acquired this knowledge from the health
      workers. Only 145/481 (30.1%) of the respondents practiced exclusive
      breastfeeding up to six months with 56/626 (8.9%) of the mothers giving
      prelacteal feeds. Although 596/629 (94.8%) of the respondents reported that the
      child does not need anything other than breast milk in the first three days of
      life, only 318/630 (50.5%) of them considered colostrum to be good. Complementary
      feeds were introduced early before six months of age and were usually not of
      adequate quality and quantity. Three hundred and ninety-one (64%) out of 603
      caregivers knew that there would be no harm to the child if exclusively breastfed
      up to six months. Most of the children's nutritional status was normal with
      25/594 (4.2%) severely stunted, 10/596 (1.7%) severely underweight and 3/594
      (0.5%) severely wasted. CONCLUSIONS: The caregiver in the communities knew about
      the recommended feeding practices, but this knowledge did not translate into good
      practice. Knowing that most of the mothers will breastfeed and have heard about
      appropriate breastfeeding, is important in the development of sustainable
      strategies required to improve feeding practices and, thus, nutritional status of
      children.

PMID- 25750658
TI  - High-throughput phenotyping of seminal root traits in wheat.
AB  - BACKGROUND: Water availability is a major limiting factor for wheat (Triticum
      aestivum L.) production in rain-fed agricultural systems worldwide. Root system
      architecture has important functional implications for the timing and extent of
      soil water extraction, yet selection for root architectural traits in breeding
      programs has been limited by a lack of suitable phenotyping methods. The aim of
      this research was to develop low-cost high-throughput phenotyping methods to
      facilitate selection for desirable root architectural traits. Here, we report two
      methods, one using clear pots and the other using growth pouches, to assess the
      angle and the number of seminal roots in wheat seedlings- two proxy traits
      associated with the root architecture of mature wheat plants. RESULTS: Both
      methods revealed genetic variation for seminal root angle and number in the panel
      of 24 wheat cultivars. The clear pot method provided higher heritability and
      higher genetic correlations across experiments compared to the growth pouch
      method. In addition, the clear pot method was more efficient - requiring less
      time, space, and labour compared to the growth pouch method. Therefore the clear
      pot method was considered the most suitable for large-scale and high-throughput
      screening of seedling root characteristics in crop improvement programs.
      CONCLUSIONS: The clear-pot method could be easily integrated in breeding programs
      targeting drought tolerance to rapidly enrich breeding populations with desirable
      alleles. For instance, selection for narrow root angle and high number of seminal
      roots could lead to deeper root systems with higher branching at depth. Such root
      characteristics are highly desirable in wheat to cope with anticipated future
      climate conditions, particularly where crops rely heavily on stored soil moisture
      at depth, including some Australian, Indian, South American, and African cropping
      regions.

PMID- 25750657
TI  - Food security for infants and young children: an opportunity for breastfeeding
      policy?
AB  - BACKGROUND: Increased global demand for imported breast milk substitutes (infant
      formula, follow-on formula and toddler milks) in Asia, particularly China, and
      food safety recalls have led to shortages of these products in high income
      countries. At the same time, commodification and trade of expressed breast milk
      have fuelled debate about its regulation, cost and distribution. In many
      economies suboptimal rates of breastfeeding continue to be perpetuated, at least
      partially, because of a failure to recognise the time, labour and opportunity
      costs of breast milk production. To date, these issues have not figured
      prominently in discussions of food security. Policy responses have been piecemeal
      and reveal conflicts between promotion and protection of breastfeeding and a
      deregulated trade environment that facilitates the marketing and consumption of
      breast milk substitutes. DISCUSSION: The elements of food security are the
      availability, accessibility, utilization and stability of supply of nutritionally
      appropriate and acceptable quantities of food. These concepts have been applied
      to food sources for infants and young children: breastfeeding, shared breast milk
      and breast milk substitutes, in accordance with World Health Organization
      (WHO)/United Nations Children's Fund (UNICEF) guidelines on infant feeding. A
      preliminary analysis indicates that a food security framework may be used to
      respond appropriately to the human rights, ethical, economic and environmental
      sustainability issues that affect the supply and affordability of different
      infant foods. SUMMARY: Food security for infants and young children is not
      possible without high rates of breastfeeding. Existing international and national
      instruments to protect, promote and support breastfeeding have not been
      implemented on a wide scale globally. These instruments need review to take into
      account the emerging trade environment that includes use of the internet, breast
      milk markets and globalised supply chains for breast milk substitutes. New
      approaches are required to handle the long-standing policy conflicts that
      surround infant and young child feeding. Placing breastfeeding in a food security
      framework may achieve the political attention and policy co-ordination required
      to accelerate breastfeeding rates in a range of economies.

PMID- 25750659
TI  - LocusTrack: Integrated visualization of GWAS results and genomic annotation.
AB  - BACKGROUND: Genome-wide association studies (GWAS) are an important tool for the
      mapping of complex traits and diseases. Visual inspection of genomic annotations
      may be used to generate insights into the biological mechanisms underlying GWAS
      identified loci. RESULTS: We developed LocusTrack, a web-based application that
      annotates and creates plots of regional GWAS results and incorporates user
      specified tracks that display annotations such as linkage disequilibrium (LD),
      phylogenetic conservation, chromatin state, and other genomic and regulatory
      elements. Currently, LocusTrack can integrate annotation tracks from the UCSC
      genome-browser as well as from any tracks provided by the user. CONCLUSION:
      LocusTrack is an easy-to-use application and can be accessed at the following
      URL: http://gump.qimr.edu.au/general/gabrieC/LocusTrack/. Users can upload and
      manage GWAS results and select from and/or provide annotation tracks using simple
      and intuitive menus. LocusTrack scripts and associated data can be downloaded
      from the website and run locally.

PMID- 25750660
TI  - Anti-foreigner Sentiment: State of the Art.
AB  - This review presents the contributions of anti-foreigner sentiment research, its
      theoretical and methodological limitations, and potential solutions for its
      further development. Six different explanations are proposed to account for the
      distribution of anti-foreigner sentiment within and across countries: economic
      competition, human capital, cultural affinity, social capital, political values,
      and the institutional environment. In this review, we argue that much of the
      extant literature heavily emphasizes variables, rather than causal mechanisms,
      and exhibits three main methodological limitations: (a) variable selection bias;
      (b) determining causality; and (c) endogeneity. We propose synthesizing
      prevailing theoretical perspectives around causal mechanisms and reformulating
      predictive models to strengthen a promising research program.

PMID- 25750661
TI  - Training safer surgeons: How do patients view the role of simulation in
      orthopaedic training?
AB  - BACKGROUND: Simulation allows training without posing risk to patient safety. It
      has developed in response to the demand for patient safety and the reduced
      training times for surgeons. Whilst there is an increasing role of simulation in
      orthopaedic training, the perception of patients and the general public of this
      novel method is yet unknown. Patients and the public were given the opportunity
      to perform a diagnostic knee arthroscopy on a virtual reality ARTHRO Mentor
      simulator. After their practice session, participants answered a validated
      questionnaire based on a 5-point Likert Scale assessing their opinions on
      arthroscopic simulation. Primary objective was observing perception of patients
      on orthopaedic virtual reality simulation. FINDINGS: There were a total of 159
      respondents, of which 86% were of the opinion that simulators are widely used in
      surgical training and 94% felt that they should be compulsory. 91% would feel
      safer having an operation by a surgeon trained on simulators, 87% desired their
      surgeon to be trained on simulators and 72% believed that additional simulator
      training resulted in better surgeons. Moreover, none of the respondents would
      want their operation to be performed by a surgeon who had not trained on a
      simulator. Cronbach's alpha was 0.969. CONCLUSIONS: There is also a clear public
      consensus for this method of training to be more widely utilised and it would
      enhance public perception of safer training of orthopaedic surgeons. This study
      of public perception provides a mandate to increase investment and infrastructure
      in orthopaedic simulation as part of promoting clinical governance.

PMID- 25750662
TI  - Measuring self-regulation in a physically active context: Psychometric analyses
      of scores derived from an observer-rated measure of self-regulation.
AB  - The purpose of this study is to report psychometric properties of scores obtained
      using a novel observer-rated measure of children's self-regulation, the Response
      to Challenge Scale (RCS). The RCS was developed to rate children's self
      regulatory abilities in a physically active context (e.g., while completing a
      physical challenge course). The RCS and other study measures were administered in
      a private school sample of 207 children. Analyses of score distributions
      indicated that the RCS was able to capture variance among children in self
      regulatory abilities; the distribution was normal for the Affective, Cognitive,
      and Total Self-Regulation scales. Validity analyses revealed significant positive
      correlations between Cognitive, Affective, Motor, and Total Self-Regulation and
      executive function task performance; significant negative correlations between
      Cognitive Regulation and teacher-rated hyperactivity and inattention; significant
      negative correlations between Affective, Motor, and Total Self-Regulation and
      teacher ratings of peer problems; and significant positive correlations between
      Cognitive and Affective Regulation and parent ratings of prosocial behavior.
      Parent and teacher rated Total Difficulties scores were both negatively
      correlated with RCS Total Self-Regulation scores. Results suggest that it is
      possible for observers to rate self-regulatory abilities in the context of
      physical activities, and that these ratings correspond with performance on tasks
      requiring executive function as well as teacher and parent ratings of children's
      difficulties.

PMID- 25750663
TI  - Preparation of water soluble carbon nanotubes and assessment of their biological
      activity in embryonic zebrafish.
AB  - Carbon nanotubes (CNTs) are currently one of the most important classes of
      nanomaterials with unique properties sparking off numerous applications in many
      fields, including electronics, material science and medicine. However,
      applications of CNTs in medicine and other biological fields are hampered by
      their insolubility in aqueous media and concerns regarding toxicity. In this
      study, seven types of CNTs, including two single-walled, one double-walled, and
      four multi-walled, were evaluated for possible toxicological effects. Soluble
      CNTs were prepared by treatment with a mixture of acids (D2SO4 and DNO3), washed
      with Milli-Q water and oven dried. Transmission electron microscopy, thermal
      gravimetric analysis, and other techniques were used to characterize the prepared
      CNTs. CNT toxicity was assessed using the embryonic zebrafish. Results showed
      that none of the CNTs studied caused significant adverse developmental effects.
      These results support the potential safe use of CNTs as components of indwelling
      medical devices and drug delivery tools.

PMID- 25750664
TI  - Stereoselective virtual screening of the ZINC database using atom pair 3D
      fingerprints.
AB  - BACKGROUND: Tools to explore large compound databases in search for analogs of
      query molecules provide a strategically important support in drug discovery to
      help identify available analogs of any given reference or hit compound by ligand
      based virtual screening (LBVS). We recently showed that large databases can be
      formatted for very fast searching with various 2D-fingerprints using the city
      block distance as similarity measure, in particular a 2D-atom pair fingerprint
      (APfp) and the related category extended atom pair fingerprint (Xfp) which
      efficiently encode molecular shape and pharmacophores, but do not perceive
      stereochemistry. Here we investigated related 3D-atom pair fingerprints to enable
      rapid stereoselective searches in the ZINC database (23.2 million 3D structures).
      RESULTS: Molecular fingerprints counting atom pairs at increasing through-space
      distance intervals were designed using either all atoms (16-bit 3DAPfp) or
      different atom categories (80-bit 3DXfp). These 3D-fingerprints retrieved
      molecular shape and pharmacophore analogs (defined by OpenEye ROCS scoring
      functions) of 110,000 compounds from the Cambridge Structural Database with equal
      or better accuracy than the 2D-fingerprints APfp and Xfp, and showed comparable
      performance in recovering actives from decoys in the DUD database. LBVS by 3DXfp
      or 3DAPfp similarity was stereoselective and gave very different analogs when
      starting from different diastereomers of the same chiral drug. Results were also
      different from LBVS with the parent 2D-fingerprints Xfp or APfp. 3D- and 2D
      fingerprints also gave very different results in LBVS of folded molecules where
      through-space distances between atom pairs are much shorter than topological
      distances. CONCLUSIONS: 3DAPfp and 3DXfp are suitable for stereoselective
      searches for shape and pharmacophore analogs of query molecules in large
      databases. Web-browsers for searching ZINC by 3DAPfp and 3DXfp similarity are
      accessible at www.gdb.unibe.ch and should provide useful assistance to drug
      discovery projects. Graphical abstractAtom pair fingerprints based on through
      space distances (3DAPfp) provide better shape encoding than atom pair
      fingerprints based on topological distances (APfp) as measured by the recovery of
      ROCS shape analogs by fp similarity.

PMID- 25750666
TI  - The role of enteric hormone GLP-2 in the response of bone markers to a mixed meal
      in postmenopausal women with type 2 diabetes mellitus.
AB  - BACKGROUND: Type 2 diabetes mellitus (T2D) is a complex disease associated with
      several chronic complications, including bone fragility and high fracture risk
      due to mechanisms not yet fully understood. The influence of the gastrointestinal
      tract and its hormones on bone remodeling has been demonstrated in healthy
      individuals. Glucagon-like peptide 2 (GLP-2), an enteric hormone secreted in
      response to nutrient intake, has been implicated as a mediator of nutrient
      effects on bone remodeling. This study aimed to analyze the dynamics of bone
      resorption marker C-terminal telopeptide of type I collagen (CTX), bone formation
      marker osteocalcin, and GLP-2 in response to a mixed meal in diabetic
      postmenopausal women. METHODS: Forty-three postmenopausal women with osteopenia
      or osteoporosis (20 controls - group CO - and 23 diabetic - group T2D) were
      subjected to a standard mixed meal tolerance test, with determination of serum
      CTX, plasma osteocalcin and serum GLP-2 concentrations at baseline and 30, 60,
      120 and 180 minutes after the meal. RESULTS: T2D women had higher body mass index
      as well as higher femoral neck and total hip bone mineral density. At baseline,
      luteinizing hormone, follicle-stimulating hormone, osteocalcin and CTX levels
      were lower in group T2D. In response to the mixed meal, CTX and osteocalcin
      levels decreased and GLP-2 levels increased in both groups. The expected CTX
      suppression in response to the mixed meal was lower in group T2D. CONCLUSIONS:
      Bone turnover markers were significantly reduced in T2D women at baseline.
      Confirming the role of nutrient intake as a stimulating factor, GLP-2 increased
      in response to the mixed meal in both groups. Importantly, CTX variation in
      response to the mixed meal was reduced in T2D women, suggesting abnormal response
      of bone remodeling to nutrient intake in T2D.

PMID- 25750668
TI  - 2015--another step along the road in a 40-year journey...

PMID- 25750667
TI  - HERV-K(HML-2) rec and np9 transcripts not restricted to disease but present in
      many normal human tissues.
AB  - BACKGROUND: Human endogenous retroviruses of the HERV-K(HML-2) group have been
      associated with the development of tumor diseases. Various HERV-K(HML-2) loci
      encode retrovirus-like proteins, and expression of such proteins is upregulated
      in certain tumor types. HERV-K(HML-2)-encoded Rec and Np9 proteins interact with
      functionally important cellular proteins and may contribute to tumor development.
      Though, the biological role of HERV-K(HML-2) transcription and encoded proteins
      in health and disease is less understood. We therefore investigated transcription
      specifically of HERV-K(HML-2) rec and np9 mRNAs in a panel of normal human
      tissues. RESULTS: We obtained evidence for rec and np9 mRNA being present in all
      examined 16 normal tissue types. A total of 18 different HERV-K(HML-2) loci were
      identified as generating rec or np9 mRNA, among them loci not present in the
      human reference genome and several of the loci harboring open reading frames for
      Rec or Np9 proteins. Our analysis identified additional alternative splicing
      events of HERV-K(HML-2) transcripts, some of them encoding variant Rec/Np9
      proteins. We also identified a second HERV-K(HML-2) locus formed by L1-mediated
      retrotransposition that is likewise transcribed in various human tissues.
      CONCLUSIONS: HERV-K(HML-2) rec and np9 transcripts from different HERV-K(HML-2)
      loci appear to be present in various normal human tissues. It is conceivable that
      Rec and Np9 proteins and variants of those proteins are part of the proteome of
      normal human tissues and thus various cell types. Transcription of HERV-K(HML-2)
      may thus also have functional relevance in normal human cell physiology.

PMID- 25750665
TI  - Harnessing the power of yeast to elucidate the role of sphingolipids in metabolic
      and signaling processes pertinent to psychiatric disorders.
AB  - The development of therapies for neuropsychiatric disorders is hampered by the
      lack of understanding of the mechanisms underlying their pathologies. While
      aberrant sphingolipid metabolism is associated with psychiatric illness, the role
      of sphingolipids in these disorders is not understood. The genetically tractable
      yeast model can be exploited in order to elucidate the cellular consequences of
      sphingolipid perturbation. Hypotheses generated from studies in yeast and tested
      in mammalian cells may contribute to our understanding of the role of
      sphingolipids in psychiatric disorders and to the development of new treatments.
      Here, we compare sphingolipid metabolism in yeast and mammalian cells, discuss
      studies implicating sphingolipids in psychiatric disorders and propose approaches
      that utilize yeast in order to elucidate sphingolipid function and identify drugs
      that target sphingolipid synthesis.

PMID- 25750669
TI  - A workshop on asthma management programs and centers in Brazil: reviewing and
      explaining concepts.
AB  - OBJECTIVE: To report the results of a workshop regarding asthma management
      programs and centers (AMPCs) in Brazil, so that they can be used as a tool for
      the improvement and advancement of current and future AMPCs. METHODS: The
      workshop consisted of five presentations and the corresponding group discussions.
      The working groups discussed the following themes: implementation of asthma
      management strategies; human resources needed for AMPCs; financial resources
      needed for AMPCs; and operational maintenance of AMPCs. RESULTS: The workshop
      involved 39 participants, from all regions of the country, representing
      associations of asthma patients (n = 3), universities (n = 7), and AMPCs (n =
      29). We found a direct relationship between a lack of planning and the failure of
      AMPCs. Based on the experiences reported during the workshop, the common
      assumptions about AMPCs in Brazil were the importance of raising awareness of
      managers; greater community participation; interdependence between primary care
      and specialized care; awareness of regionalization; and use of medications
      available in the public health system. CONCLUSIONS: Brazil already has a core of
      experience in the area of asthma management programs. The implementation of
      strategies for the management of chronic respiratory disease and their
      incorporation into health care system protocols would seem to be a natural
      progression. However, there is minimal experience in this area. Joint efforts by
      individuals with expertise in AMPCs could promote the implementation of asthma
      management strategies, thus speeding the creation of treatment networks, which
      might have a multiplier effect, precluding the need for isolated centers to start
      from zero.

PMID- 25750670
TI  - Negative impact of asthma on patients in different age groups.
AB  - OBJECTIVE: To evaluate the impact of asthma on patients in Brazil, by age group
      (12-17 years, 18-40 years, and >= 41 years). METHODS: From a survey conducted in
      Latin America in 2011, we obtained data on 400 patients diagnosed with asthma and
      residing in one of four Brazilian state capitals (Sao Paulo, Rio de Janeiro,
      Curitiba, and Salvador). The data had been collected using a standardized
      questionnaire in face-to-face interviews. For the patients who were minors, the
      parents/guardians had completed the questionnaire. The questions addressed asthma
      control, number of hospitalizations, number of emergency room visits, and
      school/work absenteeism, as well as the impact of asthma on the quality of life,
      sleep, and leisure. We stratified the data by the selected age groups. RESULTS:
      The proportions of patients who responded in the affirmative to the following
      questions were significantly higher in the 12- to 17-year age group than in the
      other two groups: "Have you had at least one episode of severe asthma that
      prevented you from playing/exercising in the last 12 months?" (p = 0.012); "Have
      you been absent from school/work in the last 12 months?" (p < 0.001); "Have you
      discontinued your asthma relief or control medication in the last 12 months?" (p
      = 0.008). In addition, 30.2% of the patients in the 12- to 17-year age group
      reported that normal physical exertion was very limiting (p = 0.010 vs. the other
      groups), whereas 14% of the patients in the >= 41-year age group described social
      activities as very limiting (p = 0.011 vs. the other groups). CONCLUSIONS: In
      this sample, asthma had a greater impact on the patients between 12 and 17 years
      of age, which might be attributable to poor treatment compliance.

PMID- 25750671
TI  - Endobronchial ultrasound-guided transbronchial needle aspiration for lung cancer
      staging: early experience in Brazil.
AB  - OBJECTIVE: Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS
      TBNA) is a minimally invasive, safe and accurate method for collecting samples
      from mediastinal and hilar lymph nodes. This study focused on the initial results
      obtained with EBUS-TBNA for lung cancer and lymph node staging at three teaching
      hospitals in Brazil. METHODS: This was a retrospective analysis of patients
      diagnosed with lung cancer and submitted to EBUS-TBNA for mediastinal lymph node
      staging. The EBUS-TBNA procedures, which involved the use of an EBUS scope, an
      ultrasound processor, and a compatible, disposable 22 G needle, were performed
      while the patients were under general anesthesia. RESULTS: Between January of
      2011 and January of 2014, 149 patients underwent EBUS-TBNA for lymph node
      staging. The mean age was 66 +/- 12 years, and 58% were male. A total of 407
      lymph nodes were sampled by EBUS-TBNA. The most common types of lung neoplasm
      were adenocarcinoma (in 67%) and squamous cell carcinoma (in 24%). For lung
      cancer staging, EBUS-TBNA was found to have a sensitivity of 96%, a specificity
      of 100%, and a negative predictive value of 85%. CONCLUSIONS: We found EBUS-TBNA
      to be a safe and accurate method for lymph node staging in lung cancer patients.

PMID- 25750672
TI  - Preoperative predictive factors for intensive care unit admission after pulmonary
      resection.
AB  - OBJECTIVE: To determine whether the use of a set of preoperative variables can
      predict the need for postoperative ICU admission. METHODS: This was a prospective
      observational cohort study of 120 patients undergoing elective pulmonary
      resection between July of 2009 and April of 2012. Prediction of ICU admission was
      based on the presence of one or more of the following preoperative
      characteristics: predicted pneumonectomy; severe/very severe COPD; severe
      restrictive lung disease; FEV1 or DLCO predicted to be < 40% postoperatively;
      SpO2 on room air at rest < 90%; need for cardiac monitoring as a precautionary
      measure; or American Society of Anesthesiologists physical status >= 3. The gold
      standard for mandatory admission to the ICU was based on the presence of one or
      more of the following postoperative characteristics: maintenance of mechanical
      ventilation or reintubation; acute respiratory failure or need for noninvasive
      ventilation; hemodynamic instability or shock; intraoperative or immediate
      postoperative complications (clinical or surgical); or a recommendation by the
      anesthesiologist or surgeon to continue treatment in the ICU. RESULTS: Among the
      120 patients evaluated, 24 (20.0%) were predicted to require ICU admission, and
      ICU admission was considered mandatory in 16 (66.6%) of those 24. In contrast,
      among the 96 patients for whom ICU admission was not predicted, it was required
      in 14 (14.5%). The use of the criteria for predicting ICU admission showed good
      accuracy (81.6%), sensitivity of 53.3%, specificity of 91%, positive predictive
      value of 66.6%, and negative predictive value of 85.4%. CONCLUSIONS: The use of
      preoperative criteria for predicting the need for ICU admission after elective
      pulmonary resection is feasible and can reduce the number of patients staying in
      the ICU only for monitoring.

PMID- 25750673
TI  - Chronic intermittent hypoxia increases encoding pigment epithelium-derived factor
      gene expression, although not that of the protein itself, in the temporal cortex
      of rats.
AB  - OBJECTIVE: Obstructive sleep apnea syndrome is mainly characterized by
      intermittent hypoxia (IH) during sleep, being associated with several
      complications. Exposure to IH is the most widely used animal model of sleep
      apnea, short-term IH exposure resulting in cognitive and neuronal impairment.
      Pigment epithelium-derived factor (PEDF) is a hypoxia-sensitive factor acting as
      a neurotrophic, neuroprotective, and antiangiogenic agent. Our study analyzed
      performance on learning and cognitive tasks, as well as PEDF gene expression and
      PEDF protein expression in specific brain structures, in rats exposed to long
      term IH. METHODS: Male Wistar rats were exposed to IH (oxygen concentrations of
      21-5%) for 6 weeks-the chronic IH (CIH) group-or normoxia for 6 weeks-the control
      group. After CIH exposure, a group of rats were allowed to recover under normoxic
      conditions for 2 weeks (the CIH+N group). All rats underwent the Morris water
      maze test for learning and memory, PEDF gene expression and PEDF protein
      expression in the hippocampus, frontal cortex, and temporal cortex being
      subsequently assessed. RESULTS: The CIH and CIH+N groups showed increased PEDF
      gene expression in the temporal cortex, PEDF protein expression remaining
      unaltered. PEDF gene expression and PEDF protein expression remained unaltered in
      the frontal cortex and hippocampus. Long-term exposure to IH did not affect
      cognitive function. CONCLUSIONS: Long-term exposure to IH selectively increases
      PEDF gene expression at the transcriptional level, although only in the temporal
      cortex. This increase is probably a protective mechanism against IH-induced
      injury.

PMID- 25750674
TI  - Community-acquired pneumonia: economics of inpatient medical care vis-a-vis
      clinical severity.
AB  - OBJECTIVE: To assess the direct and indirect costs of diagnosing and treating
      community-acquired pneumonia (CAP), correlating those costs with CAP severity at
      diagnosis and identifying the major cost drivers. METHODS: This was a prospective
      cost analysis study using bottom-up costing. Clinical severity and mortality risk
      were assessed with the pneumonia severity index (PSI) and the mental Confusion
      Urea-Respiratory rate-Blood pressure-age >= 65 years (CURB-65) scale,
      respectively. The sample comprised 95 inpatients hospitalized for newly diagnosed
      CAP. The analysis was run from a societal perspective with a time horizon of one
      year. RESULTS: Expressed as mean +/- standard deviation, in Euros, the direct and
      indirect medical costs per CAP patient were 696 +/- 531 and 410 +/- 283,
      respectively, the total per-patient cost therefore being 1,106 +/- 657. The
      combined budget impact of our patient cohort, in Euros, was 105,087 (66,109 and
      38,979 in direct and indirect costs, respectively). The major cost drivers, in
      descending order, were the opportunity cost (lost productivity); diagnosis and
      treatment of comorbidities; and administration of medications, oxygen, and blood
      derivatives. The CURB-65 and PSI scores both correlated with the indirect costs
      of CAP treatment. The PSI score correlated positively with the overall frequency
      of use of health care services. Neither score showed any clear relationship with
      the direct costs of CAP treatment. CONCLUSIONS: Clinical severity at admission
      appears to be unrelated to the costs of CAP treatment. This is mostly
      attributable to unwarranted hospital admission (or unnecessarily long hospital
      stays) in cases of mild pneumonia, as well as to over-prescription of
      antibiotics. Authorities should strive to improve adherence to guidelines and
      promote cost-effective prescribing practices among physicians in southeastern
      Europe.

PMID- 25750675
TI  - Diagnostic accuracy of the Bedside Lung Ultrasound in Emergency protocol for the
      diagnosis of acute respiratory failure in spontaneously breathing patients.
AB  - OBJECTIVE: Bedside lung ultrasound (LUS) is a noninvasive, readily available
      imaging modality that can complement clinical evaluation. The Bedside Lung
      Ultrasound in Emergency (BLUE) protocol has demonstrated a high diagnostic
      accuracy in patients with acute respiratory failure (ARF). Recently, bedside LUS
      has been added to the medical training program of our ICU. The aim of this study
      was to investigate the accuracy of LUS based on the BLUE protocol, when performed
      by physicians who are not ultrasound experts, to guide the diagnosis of ARF.
      METHODS: Over a one-year period, all spontaneously breathing adult patients
      consecutively admitted to the ICU for ARF were prospectively included. After
      training, 4 non-ultrasound experts performed LUS within 20 minutes of patient
      admission. They were blinded to patient medical history. LUS diagnosis was
      compared with the final clinical diagnosis made by the ICU team before patients
      were discharged from the ICU (gold standard). RESULTS: Thirty-seven patients were
      included in the analysis (mean age, 73.2 +/- 14.7 years; APACHE II, 19.2 +/-
      7.3). LUS diagnosis had a good agreement with the final diagnosis in 84% of
      patients (overall kappa, 0.81). The most common etiologies for ARF were pneumonia
      (n = 17) and hemodynamic lung edema (n = 15). The sensitivity and specificity of
      LUS as measured against the final diagnosis were, respectively, 88% and 90% for
      pneumonia and 86% and 87% for hemodynamic lung edema. CONCLUSIONS: LUS based on
      the BLUE protocol was reproducible by physicians who are not ultrasound experts
      and accurate for the diagnosis of pneumonia and hemodynamic lung edema.

PMID- 25750676
TI  - Chronic rhinosinusitis and nasal polyposis in cystic fibrosis: update on
      diagnosis and treatment.
AB  - Although cystic fibrosis (CF) is an irreversible genetic disease, advances in
      treatment have increased the life expectancy of CF patients. Upper airway
      involvement, which is mainly due to pathological changes in the paranasal
      sinuses, is prevalent in CF patients, although many are only mildly symptomatic
      (with few symptoms). The objective of this literature review was to discuss the
      pathophysiology and current therapeutic management of chronic rhinosinusitis
      (CRS) in CF patients. The review was based on current evidence, which was
      classified in accordance with the Oxford Centre for Evidence-Based Medicine
      criteria. When symptomatic, CRS with nasal polyps can affect quality of life and
      can lead to pulmonary exacerbations, given that the paranasal sinuses can be
      colonized with pathogenic bacteria, especially Pseudomonas aeruginosa. Infection
      with P. aeruginosa plays a crucial role in morbidity and mortality after lung
      transplantation in CF patients. Although clinical treatment of the upper airways
      is recommended as initial management, this recommendation is often extrapolated
      from studies of CRS in the general population. When sinonasal disease is
      refractory to noninvasive therapy, surgery is indicated. Further studies are
      needed in order to gain a better understanding of upper airway involvement and
      improve the management of CRS in CF patients, with the objective of preserving
      lung function and avoiding unnecessary invasive procedures. 

PMID- 25750677
TI  - Risk factors associated with adverse reactions to antituberculosis drugs.
AB  - This review sought to identify the available scientific evidence on risk factors
      associated with adverse reactions to antituberculosis drugs. We performed a
      systematic review of studies published in the 1965-2012 period and indexed in the
      MEDLINE and LILACS databases. A total of 1,389 articles were initially selected.
      After reading their abstracts, we selected 85 studies. Of those 85 studies, 16
      were included in the review. Risk factors for adverse reactions to
      antituberculosis drugs included age > 60 years, treatment regimens, alcoholism,
      anemia, and HIV co-infection, as well as sodium, iron, and albumin deficiency.
      Protective factors against hepatic adverse effects of antituberculosis drugs
      included being male (combined OR = 0.38; 95% CI: 0.20-0.72) and showing a
      rapid/intermediate N-acetyltransferase 2 acetylator phenotype (combined OR =
      0.41; 95% CI: 0.18-0.90). There is evidence to support the need for management of
      adverse reactions to antituberculosis drugs at public health care facilities. 

PMID- 25750678
TI  - Video-assisted thoracoscopic implantation of a diaphragmatic pacemaker in a child
      with tetraplegia: indications, technique, and results.
AB  - We report the case of a child with tetraplegia after cervical trauma, who
      subsequently underwent diaphragmatic pacemaker implantation. We reviewed the
      major indications for diaphragmatic pacing and the types of devices employed. We
      highlight the unequivocal benefit of diaphragmatic pacing in the social and
      educational reintegration of individuals with tetraplegia. 

PMID- 25750679
TI  - Nonadherence to treatment in lung transplant recipients: a matter of life and
      death.

PMID- 25750680
TI  - Anxiety, depression, and motivation for smoking cessation in hospitalized
      patients with and without cancer.

PMID- 25750681
TI  - Incidence of spontaneous subdural hematoma in incident cases of pulmonary
      arterial hypertension: a registry of cases occurring over a five-year period.

PMID- 25750682
TI  - Hibernoma: an uncommon cause of a pleural mass.

PMID- 25750683
TI  - The Societal Importance of Embracing Counterintuitive Thought in Science:
      Assisted Exercise in Preterm Infants for Long-term Health Outcomes.
AB  - For research to lead to progressive change, scientists and society must embrace
      what may seem counterintuitive. While there is often resistance to changing views
      of what we presume to already understand, we must be open to evolving knowledge
      and evidence. Our research is examining the effect of a novel intervention
      designed to increase physical activity of premature babies in their first year of
      life on: (1) body composition, (2) associated biochemical and cellular mechanisms
      of growth and inflammation, and (3) quality of maternal care. This study is novel
      because it is counterintuitive to prevailing knowledge of the care and treatment
      of infants born prematurely. Traditionally, we swaddle infants and restrict their
      movement in order to minimize energy expenditure. We are proposing the opposite:
      to increase energy expenditure in a systematic, controlled way in order to
      increase muscle mass and bone density, with the ultimate goal of preventing
      diseases associated with lack of muscle mass or bone density. Our research
      actively engages the mothers in the study by learning about their perceptions and
      their experiences of doing the exercise with their infants because the mothers,
      too, are aware of the prevailing views that are counter to what they are being
      asked to do. The mothers have taught us, however, that they are willing to
      participate in this exercise study, while paradoxically also viewing their
      infants as "fragile" and are fearful of hurting their infants. Our thesis in this
      research-based paper is that science and society must work in tandem to be
      effective.

PMID- 25750684
TI  - Design and Synthesis of an Artificial Pulmonary Pleura for High Throughput
      Studies in Acellular Human Lungs.
AB  - Whole organ decellularization of complex organs, such as lungs, presents a unique
      opportunity for use of acellular scaffolds for ex vivo tissue engineering or for
      studying cell-extracellular matrix interactions ex vivo. A growing body of
      literature investigating decellularizing and recellularizing rodent lungs has
      provided important proof of concept models and rodent lungs are readily available
      for high throughput studies. In contrast, comparable progress in large animal and
      human lungs has been impeded owing to more limited availability and difficulties
      in handling larger tissue. While the use of smaller segments of acellular large
      animal or human lungs would maximize usage from a single lung, excision of small
      acellular segments compromises the integrity of the pleural layer, leaving the
      terminal ends of blood vessels and airways exposed. We have developed a novel
      pleural coating using non-toxic ionically crosslinked alginate or
      photocrosslinked methacrylated alginate which can be applied to excised acellular
      lung segments, permits inflation of small segments, and significantly enhances
      retention of cells inoculated through cannulated airways or blood vessels.
      Further, photocrosslinking methacrylated alginate, using eosin Y and
      triethanolamine (TEOA) at 530nm wavelength, results in a mechanically stable
      pleural coating that permits effective cyclic 3-dimensional stretch, i.e.
      mechanical ventilation, of individual segments.

PMID- 25750685
TI  - Visual search for feature conjunctions: an fMRI study comparing alcohol-related
      neurodevelopmental disorder (ARND) to ADHD.
AB  - BACKGROUND: Alcohol-related neurodevelopmental disorder (ARND) falls under the
      umbrella of fetal alcohol spectrum disorder (FASD). Diagnosis of ARND is
      difficult because individuals do not demonstrate the characteristic facial
      features associated with fetal alcohol syndrome (FAS). While attentional problems
      in ARND are similar to those found in attention-deficit/hyperactivity disorder
      (ADHD), the underlying impairment in attention pathways may be different.
      METHODS: Functional magnetic resonance imaging (fMRI) and diffusion tensor
      imaging (DTI) was conducted at 3 T. Sixty-three children aged 10 to 14 years
      diagnosed with ARND, ADHD, and typically developing (TD) controls performed a
      single-feature and a feature-conjunction visual search task. RESULTS: Dorsal and
      ventral attention pathways were activated during both attention tasks in all
      groups. Significantly greater activation was observed in ARND subjects during a
      single-feature search as compared to TD and ADHD groups, suggesting ARND subjects
      require greater neural recruitment to perform this simple task. ARND subjects
      appear unable to effectively use the very efficient automatic perceptual 'pop
      out' mechanism employed by TD and ADHD groups during presentation of the
      disjunction array. By comparison, activation was lower in ARND compared to TD and
      ADHD subjects during the more difficult conjunction search task as compared to
      the single-feature search. Analysis of DTI data using tract-based spatial
      statistics (TBSS) showed areas of significantly lower fractional anisotropy (FA)
      and higher mean diffusivity (MD) in the right inferior longitudinal fasciculus
      (ILF) in ARND compared to TD subjects. Damage to the white matter of the ILF may
      compromise the ventral attention pathway and may require subjects to use the
      dorsal attention pathway, which is associated with effortful top-down processing,
      for tasks that should be automatic. Decreased functional activity in the right
      temporoparietal junction (TPJ) of ARND subjects may be due to a reduction in the
      white matter tract's ability to efficiently convey information critical to
      performance of the attention tasks. CONCLUSIONS: Limited activation patterns in
      ARND suggest problems in information processing along the ventral frontoparietal
      attention pathway. Poor integrity of the ILF, which connects the functional
      components of the ventral attention network, in ARND subjects may contribute to
      the attention deficits characteristic of the disorder.

PMID- 25750686
TI  - A national survey of Rett syndrome: behavioural characteristics.
AB  - BACKGROUND: The aim was to gain a UK national sample of people with Rett syndrome
      (RTT) across the age range and compare their characteristics using a variety of
      relevant behavioural measures with a well-chosen contrast group. METHODS: The
      achieved sample was 91 girls and women, aged from 4 to 47 years, of whom 71 were
      known to be MECP2 positive. The contrast group (n = 66), matched for age, gender,
      language and self-help skills, comprised individuals with six other syndromes
      associated with intellectual disability. Parental questionnaire measures of RTT
      specific characteristics, impulsivity, overactivity, mood, interest and pleasure,
      repetitive behaviour and self-injury were administered. RESULTS: Hand
      stereotypies, breathing irregularities, night-time unrest and anxiety or
      inappropriate fear were commonly reported among the RTT sample. Problems of low
      mood were also reported as common. However, mood and interest and pleasure were
      no lower than found in the contrast group. In addition, self-injury was lower
      than in the contrast group and was associated with factors found to predict self
      injury in other groups of people with severe intellectual disabilities.
      CONCLUSIONS: There is variability in the manifestation of problem behaviours
      potentially associated with the syndrome across individuals, with some more
      severely affected in most areas than others. Some of this variability appears to
      be underpinned by genetic mutation.

PMID- 25750688
TI  - Physiological Differences Across Populations Reflecting Early Life and Later Life
      Nutritional Status and Later Life Risk for Chronic Disease.

PMID- 25750687
TI  - Moving beyond Mindfulness: Defining Equanimity as an Outcome Measure in
      Meditation and Contemplative Research.
AB  - In light of a growing interest in contemplative practices such as meditation, the
      emerging field of contemplative science has been challenged to describe and
      objectively measure how these practices affect health and well-being. While
      "mindfulness" itself has been proposed as a measurable outcome of contemplative
      practices, this concept encompasses multiple components, some of which, as we
      review here, may be better characterized as equanimity. Equanimity can be defined
      as an even-minded mental state or dispositional tendency toward all experiences
      or objects, regardless of their origin or their affective valence (pleasant,
      unpleasant, or neutral). In this article we propose that equanimity be used as an
      outcome measure in contemplative research. We first define and discuss the inter
      relationship between mindfulness and equanimity from the perspectives of both
      classical Buddhism and modern psychology and present existing meditation
      techniques for cultivating equanimity. We then review psychological,
      physiological, and neuroimaging methods that have been used to assess equanimity,
      either directly or indirectly. In conclusion, we propose that equanimity captures
      potentially the most important psychological element in the improvement of well
      being, and therefore should be a focus in future research studies.

PMID- 25750689
TI  - Spatial perturbation with synthetic protein scaffold reveals robustness of
      asymmetric cell division.
AB  - Asymmetric cell division is an important mechanism for creating diversity in a
      cellular population. Stem cells commonly perform asymmetric division to generate
      both a daughter stem cell for self-renewal and a more differentiated daughter
      cell to populate the tissue. During asymmetric cell division, protein cell fate
      determinants asymmetrically localize to the opposite poles of a dividing cell to
      cause distinct cell fate. However, it remains unclear whether cell fate
      determination is robust to fluctuations and noise during this spatial allocation
      process. To answer this question, we engineered Caulobacter, a bacterial model
      for asymmetric division, to express synthetic scaffolds with modular protein
      interaction domains. These scaffolds perturbed the spatial distribution of the
      PleC-DivJ-DivK phospho-signaling network without changing their endogenous
      expression levels. Surprisingly, enforcing symmetrical distribution of these cell
      fate determinants did not result in symmetric daughter fate or any morphological
      defects. Further computational analysis suggested that PleC and DivJ form a
      robust phospho-switch that can tolerate high amount of spatial variation. This
      insight may shed light on the presence of similar phospho-switches in stem cell
      asymmetric division regulation. Overall, our study demonstrates that synthetic
      protein scaffolds can provide a useful tool to probe biological systems for
      better understanding of their operating principles.

PMID- 25750691
TI  - Novel Biomarkers: Utility in Patients with Acute Chest Pain and Relationship to
      Coronary Artery Disease on Coronary CT Angiography.
AB  - Acute chest pain remains one of the most common patient presentations encountered
      in the emergency department. With the evolution of biomarkers and improvement in
      cardiac imaging there has been advancement in risk stratification of patients,
      but millions of dollars continue to be spent in the assessment of chest pain.
      Investigators have explored possible comparative alternatives to the traditional
      work up of chest pain. In this review, we will discuss the current state of
      biomarker use in the evaluation of acute chest pain. We will review established
      and emerging circulating biomarkers and their addition to cardiac CT for
      appropriate diagnosis of coronary artery disease.

PMID- 25750692
TI  - Dye-Staining Angioscopy for Coronary Artery Disease.
AB  - Novel imaging techniques using biomarkers have clarified the mechanisms of
      hitherto unanswered or misunderstood phenomena of coronary artery disease and
      enabled evaluation of myocardial blood and tissue fluid flows in vivo. Dye
      staining coronary angioscopy using Evans blue (EB) as the biomarker can visualize
      fibrin and damaged endothelial cells, revealing that the so-called platelet
      thrombus is frequently a fibrin-rich thrombus; occlusive transparent fibrin
      thrombus, but not platelet thrombus, is not infrequently a cause of acute
      coronary syndrome; "fluffy" coronary luminal surface is caused by fibrin threads
      arising from damaged endothelial cells and is a residue of an occlusive thrombus
      after autolysis in patients with acute coronary syndrome without angiographically
      demonstrable coronary stenosis; and web or membrane-like fibrin thrombus is a
      cause of stent edge restenosis. Fluorescent angioscopy using visual or near
      infrared light wavelengths is now used clinically for molecular imaging of the
      substances such as lipoproteins and cholesterol that constitute coronary plaques.
      Dye-staining cardioscopy using EB or fluorescein enables direct and real-time
      visualization of subendocardial microcirculation.

PMID- 25750690
TI  - Bayesian Models for fMRI Data Analysis.
AB  - Functional magnetic resonance imaging (fMRI), a noninvasive neuroimaging method
      that provides an indirect measure of neuronal activity by detecting blood flow
      changes, has experienced an explosive growth in the past years. Statistical
      methods play a crucial role in understanding and analyzing fMRI data. Bayesian
      approaches, in particular, have shown great promise in applications. A remarkable
      feature of fully Bayesian approaches is that they allow a flexible modeling of
      spatial and temporal correlations in the data. This paper provides a review of
      the most relevant models developed in recent years. We divide methods according
      to the objective of the analysis. We start from spatio-temporal models for fMRI
      data that detect task-related activation patterns. We then address the very
      important problem of estimating brain connectivity. We also touch upon methods
      that focus on making predictions of an individual's brain activity or a clinical
      or behavioral response. We conclude with a discussion of recent integrative
      models that aim at combining fMRI data with other imaging modalities, such as
      EEG/MEG and DTI data, measured on the same subjects. We also briefly discuss the
      emerging field of imaging genetics.

PMID- 25750693
TI  - SYMMETRIC NON-RIGID IMAGE REGISTRATION VIA AN ADAPTIVE QUASI-VOLUME-PRESERVING
      CONSTRAINT.
AB  - The standard implementation of non-rigid image registration is asymmetric, even
      though symmetry might be an intrinsic attribute of the particular application,
      e.g., pairwise image alignment. Current approaches to restore symmetry to non
      rigid registration, although successful in achieving inverse-consistency,
      generally alter the objective function through implicit inclusion of a non
      uniform weight in the integral that is computed on the native space of an input
      image. This inhomogeneous integral measure, which varies through the course of
      the registration, results in regional biases by allowing image regions to
      contribute differently to the objective function. In this work, instead of
      symmetrizing the objective function, we address the root of the problem: the non
      uniformity of the integral in both the asymmetric and the symmetrized
      implementations. We introduce a new quasi-volume-preserving constraint that keeps
      the forward and backward objective functions arbitrarily close to each other -
      hence the registration symmetry - without compromising the uniformity of the
      integrals. We show the advantages of our method through experiments on synthetic
      images and real X-ray and MRI data.

PMID- 25750694
TI  - Capacity building for long-term community-academic health partnership outcomes.
AB  - Too often, populations experiencing the greatest burden of disease and
      disparities in health outcomes are left out of or ineffectively involved in
      academic-led efforts to address issues that impact them the most. Community-based
      participatory research (CBPR) is an approach increasingly being used to address
      these issues, but the science of CBPR is still viewed by many as a nascent field.
      Important to the development of the science of CBPR is documentation of the
      partnership process, particularly capacity building activities important to
      establishing the CBPR research infrastructure. This paper uses a CBPR Logic Model
      as a structure for documenting partnership capacity building activities of a long
      term community-academic partnership addressing public health issues in Arkansas,
      U.S. Illustrative activities, programs, and experiences are described for each of
      the model's four constructs: context, group dynamics, interventions, and
      outcomes. Lessons learned through this process were: capacity building is
      required by both academic and community partners; shared activities provide a
      common base of experiences and expectations; and creating a common language
      facilitates dialogue about difficult issues. Development of community
      partnerships with one institutional unit promoted community engagement
      institution-wide, enhanced individual and partnership capacity, and increased
      opportunity to address priority issues.

PMID- 25750695
TI  - P2X4 receptor-eNOS signaling pathway in cardiac myocytes as a novel protective
      mechanism in heart failure.
AB  - We have demonstrated using immunoprecipitation and immunostaining a novel
      physical association of the P2X4 receptor (P2X4R), a ligand-gated ion channel,
      with the cardioprotective, calcium-dependent enzyme endothelial nitric oxide
      synthase (eNOS). Treatment of murine ventricular myocytes with the P2XR agonist 2
      methylthioATP (2-meSATP) to induce a current (mainly Na(+)) increased the
      formation of nitric oxide (NO), as measured using a fluorescent probe. Possible
      candidates for downstream effectors mediating eNOS activity include cyclic GMP
      and PKG or cellular protein nitrosylation. A cardiac-specific P2X4R
      overexpressing mouse line was protected from heart failure (HF) with improved
      cardiac function and survival in post-infarct, pressure overload, and
      calsequestrin (CSQ) overexpression models of HF. Although the role of the P2X4R
      in other tissues such as the endothelium and monocytes awaits characterization in
      tissue-specific KO, cardiac-specific activation of eNOS may be more
      cardioprotective than an increased activity of global systemic eNOS. The intra
      myocyte formation of NO may be more advantageous over NO derived externally from
      a donor. A small molecule drug stimulating this sarcolemmal pathway or gene
      therapy-mediated overexpression of the P2X4R in cardiac myocytes may represent a
      new therapy for both ischemic and pressure overloaded HF. 

PMID- 25750696
TI  - Machine learning applications in cancer prognosis and prediction.
AB  - Cancer has been characterized as a heterogeneous disease consisting of many
      different subtypes. The early diagnosis and prognosis of a cancer type have
      become a necessity in cancer research, as it can facilitate the subsequent
      clinical management of patients. The importance of classifying cancer patients
      into high or low risk groups has led many research teams, from the biomedical and
      the bioinformatics field, to study the application of machine learning (ML)
      methods. Therefore, these techniques have been utilized as an aim to model the
      progression and treatment of cancerous conditions. In addition, the ability of ML
      tools to detect key features from complex datasets reveals their importance. A
      variety of these techniques, including Artificial Neural Networks (ANNs),
      Bayesian Networks (BNs), Support Vector Machines (SVMs) and Decision Trees (DTs)
      have been widely applied in cancer research for the development of predictive
      models, resulting in effective and accurate decision making. Even though it is
      evident that the use of ML methods can improve our understanding of cancer
      progression, an appropriate level of validation is needed in order for these
      methods to be considered in the everyday clinical practice. In this work, we
      present a review of recent ML approaches employed in the modeling of cancer
      progression. The predictive models discussed here are based on various supervised
      ML techniques as well as on different input features and data samples. Given the
      growing trend on the application of ML methods in cancer research, we present
      here the most recent publications that employ these techniques as an aim to model
      cancer risk or patient outcomes. 

PMID- 25750697
TI  - Systems-based approaches to unravel multi-species microbial community
      functioning.
AB  - Some of the most transformative discoveries promising to enable the resolution of
      this century's grand societal challenges will most likely arise from
      environmental science and particularly environmental microbiology and
      biotechnology. Understanding how microbes interact in situ, and how microbial
      communities respond to environmental changes remains an enormous challenge for
      science. Systems biology offers a powerful experimental strategy to tackle the
      exciting task of deciphering microbial interactions. In this framework, entire
      microbial communities are considered as metaorganisms and each level of
      biological information (DNA, RNA, proteins and metabolites) is investigated along
      with in situ environmental characteristics. In this way, systems biology can help
      unravel the interactions between the different parts of an ecosystem ultimately
      responsible for its emergent properties. Indeed each level of biological
      information provides a different level of characterisation of the microbial
      communities. Metagenomics, metatranscriptomics, metaproteomics, metabolomics and
      SIP-omics can be employed to investigate collectively microbial community
      structure, potential, function, activity and interactions. Omics approaches are
      enabled by high-throughput 21st century technologies and this review will discuss
      how their implementation has revolutionised our understanding of microbial
      communities. 

PMID- 25750698
TI  - The role of water in protein's behavior: The two dynamical crossovers studied by
      NMR and FTIR techniques.
AB  - The role the solvent plays in determining the biological activity of proteins is
      of primary importance. Water is the solvent of life and proteins need at least a
      water monolayer covering their surface in order to become biologically active. We
      study how the properties of water and the effect of its coupling with the
      hydrophilic moieties of proteins govern the regime of protein activity. In
      particular we follow, by means of Fourier Transform Infrared spectroscopy, the
      thermal evolution of the amide vibrational modes of hydrated lysozyme in the
      temperature interval 180 K < T < 350 K. In such a way we are able to observe the
      thermal limit of biological activity characterizing hydrated lysozyme. Finally we
      focus on the region of lysozyme thermal denaturation by following the evolution
      of the proton Nuclear Magnetic Resonance (NMR) spectra for 298 K < T < 366 K with
      the High-Resolution Magic Angle Spinning probe. Our data suggest that the
      hydrogen bond coupling between hydration water and protein hydrophilic groups is
      crucial in triggering the main mechanisms that define the enzymatic activity of
      proteins. 

PMID- 25750699
TI  - Computationally Modeling Lipid Metabolism and Aging: A Mini-review.
AB  - One of the greatest challenges in biology is to improve the understanding of the
      mechanisms which underpin aging and how these affect health. The need to better
      understand aging is amplified by demographic changes, which have caused a gradual
      increase in the global population of older people. Aging western populations have
      resulted in a rise in the prevalence of age-related pathologies. Of these
      diseases, cardiovascular disease is the most common underlying condition in older
      people. The dysregulation of lipid metabolism due to aging impinges significantly
      on cardiovascular health. However, the multifaceted nature of lipid metabolism
      and the complexities of its interaction with aging make it challenging to
      understand by conventional means. To address this challenge computational
      modeling, a key component of the systems biology paradigm is being used to study
      the dynamics of lipid metabolism. This mini-review briefly outlines the key
      regulators of lipid metabolism, their dysregulation, and how computational
      modeling is being used to gain an increased insight into this system. 

PMID- 25750700
TI  - Stage-specific control of stem cell niche architecture in the Drosophila testis
      by the posterior Hox gene Abd-B.
AB  - A fundamental question in biology is how complex structures are maintained after
      their initial specification. We address this question by reviewing the role of
      the Hox gene Abd-B in Drosophila testis organogenesis, which proceeds through
      embryonic, larval and pupal stages to reach maturation in adult stages. The data
      presented in this review highlight a cell- and stage-specific function of Abd-B,
      since the mechanisms regulating stem cell niche positioning and architecture at
      different stages seem to be different despite the employment of similar factors.
      In addition to its described role in the male embryonic gonads, sustained
      activity of Abd-B in the pre-meiotic germline spermatocytes during larval stages
      is required to maintain the architecture of the stem cell niche by regulating
      betaPS-integrin localization in the neighboring somatic cyst cells. Loss of Abd-B
      is associated with cell non-autonomous effects within the niche, leading to a
      dramatic reduction of pre-meiotic cell populations in adult testes.
      Identification of Abd-B target genes revealed that Abd-B mediates its effects by
      controlling the activity of the sevenless ligand Boss via its direct targets
      Src42A and Sec63. During adult stages, when testis morphogenesis is completed
      with the addition of the acto-myosin sheath originating from the genital disc,
      stem cell niche positioning and integrity are regulated by Abd-B activity in the
      acto-myosin sheath whereas integrin acts in an Abd-B independent way. It seems
      that the occurrence of new cell types and cell interactions in the course of
      testis organogenesis made it necessary to adapt the system to the new cellular
      conditions by reusing the same players for testis stem cell niche positioning in
      an alternative manner. 

PMID- 25750701
TI  - A new paradigm for known metabolite identification in metabonomics/metabolomics:
      metabolite identification efficiency.
AB  - A new paradigm is proposed for assessing confidence in the identification of
      known metabolites in metabonomics studies using NMR spectroscopy approaches. This
      new paradigm is based upon the analysis of the amount of metabolite
      identification information retrieved from NMR spectra relative to the molecular
      size of the metabolite. Several new indices are proposed including: metabolite
      identification efficiency (MIE) and metabolite identification carbon efficiency
      (MICE), both of which can be easily calculated. These indices, together with some
      guidelines, can be used to provide a better indication of known metabolite
      identification confidence in metabonomics studies than existing methods. Since
      known metabolite identification in untargeted metabonomics studies is one of the
      key bottlenecks facing the science currently, it is hoped that these concepts
      based on molecular spectroscopic informatics, will find utility in the field. 

PMID- 25750702
TI  - Possible Biomarkers for the Early Detection of HIV-associated Heart Diseases: A
      Proteomics and Bioinformatics Prediction.
AB  - The frequency of cardiovascular disorders is increasing in HIV-infected
      individuals despite a significant reduction in the viral load by antiretroviral
      therapies (ART). Since the CD4 + T-cells are responsible for the viral load as
      well as immunological responses, we hypothesized that chronic HIV-infection of T
      cells produces novel proteins/enzymes that cause cardiac dysfunctions. To
      identify specific factors that might cause cardiac disorders without the
      influence of numerous cofactors produced by other pathogenic microorganisms that
      co-inhabit most HIV-infected individuals, we analyzed genome-wide proteomes of a
      CD4 + T-cell line at different stages of HIV replication and cell growth over > 6
      months. Subtractive analyses of several hundred differentially regulated proteins
      from HIV-infected and uninfected counterpart cells and comparisons with proteins
      expressed from the same cells after treating with the antiviral drug
      Zidovudine/AZT and inhibiting virus replication, identified a well-coordinated
      network of 12 soluble/diffusible proteins in HIV-infected cells. Functional
      categorization, bioinformatics and statistical analyses of each protein predicted
      that the expression of cardiac-specific Ca2 + kinase together with multiple Ca2 +
      release channels causes a sustained overload of Ca2 + in the heart which induces
      fetal/cardiac myosin heavy chains (MYH6 and MYH7) and a myosin light-chain
      kinase. Each of these proteins has been shown to cause cardiac stress,
      arrhythmia, hypertrophic signaling, cardiomyopathy and heart failure (p = 8 * 10(
      11)). Translational studies using the newly discovered proteins produced by HIV
      infection alone would provide additional biomarkers that could be added to the
      conventional markers for an early diagnosis and/or development of specific
      therapeutic interventions for heart diseases in HIV-infected individuals. 

PMID- 25750703
TI  - Antiviral Drug- and Multidrug Resistance in Cytomegalovirus Infected SCT
      Patients.
AB  - In pediatric and adult patients after stem cell transplantation (SCT)
      disseminated infections caused by human cytomegalovirus (HCMV) can cause life
      threatening diseases. For treatment, the three antivirals ganciclovir (GCV),
      foscarnet (PFA) and cidofovir (CDV) are approved and most frequently used.
      Resistance to all of these antiviral drugs may induce a severe problem in this
      patient cohort. Responsible for resistance phenomena are mutations in the HCMV
      phosphotransferase-gene (UL97) and the polymerase-gene (UL54). Most frequently
      mutations in the UL97-gene are associated with resistance to GCV. Resistance
      against all three drugs is associated to mutations in the UL54-gene. Monitoring
      of drug resistance by genotyping is mostly done by PCR-based Sanger sequencing.
      For phenotyping with cell culture the isolation of HCMV is a prerequisite. The
      development of multidrug resistance with mutation in both genes is rare, but it
      is often associated with a fatal outcome. The manifestation of multidrug
      resistance is mostly associated with combined UL97/UL54-mutations. Normally,
      mutations in the UL97 gene occur initially followed by UL54 mutation after
      therapy switch. The appearance of UL54-mutation alone without any detection of
      UL97-mutation is rare. Interestingly, in a number of patients the UL97 mutation
      could be detected in specific compartments exclusively and not in blood. 

PMID- 25750704
TI  - Neuroprotection Mediated by P2Y13 Nucleotide Receptors in Neurons.
AB  - ADP-specific P2Y13 receptor constitutes one of the most recently identified
      nucleotide receptor and the understanding of their physiological role is
      currently under investigation. Cerebellar astrocytes and granule neurons provide
      excellent models to study P2Y13 expression and function since the first
      identification of ADP-evoked calcium responses not attributable to the related
      P2Y1 receptor was performed in these cell populations. In this regard, all
      responses induced by ADP analogues in astrocytes resulted to be Gi-coupled
      activities mediated by P2Y13 instead of P2Y1 receptors. Similarly, both glycogen
      synthase kinase-3 (GSK3) and ERK1/2 signaling triggered by 2MeSADP in cerebellar
      granule neurons were also dependent on Gi-coupled receptors, and mediated by PI3K
      activity. In granule neurons, P2Y13 receptor was specifically coupled to the main
      neuronal survival PI3K/Akt-cascade targeting GSK3 phosphorylation. GSK3
      inhibition led to nuclear translocation of transcriptional targets, including
      beta-catenin and Nrf2. The activation of the Nrf2/heme oxygenase-1 (HO-1) axis
      was responsible for the prosurvival effect against oxidative stress. In addition,
      P2Y13-mediated ERK1/2 signaling in granule neurons also triggered activation of
      transcription factors, such as CREB, which underlined the antiapoptotic action
      against glutamate-induced excitotoxicity. Finally, a novel signaling mechanism
      has been recently described for a P2Y13 receptor in granule neurons that involved
      the expression of a dual protein phosphatase, DUSP2. This activity contributed to
      regulate MAPK activation after genotoxic stress. In conclusion, P2Y13 receptors
      harbored in cerebellar astrocytes and granule neurons exhibit specific signaling
      properties that link them to specialized functions at the level of
      neuroprotection and trophic activity in both cerebellar cell populations. 

PMID- 25750705
TI  - Hypersensitive pupillary light reflex in infants at risk for autism.
AB  - BACKGROUND: Post mortem brain tissue data and animal modeling work indicate
      cholinergic disruptions in autism. Moreover, the cholinergic system plays a key
      role in the early neurodevelopmental processes believed to be derailed early in
      life in individuals with the disorder. Yet, there is no data from human infants
      supporting a developmentally important role of this neurotransmitter system.
      Because the pupillary light reflex depends largely on cholinergic synaptic
      transmission, we assessed this reflex in a sample of infants at risk for autism
      as well as infants at low (average) risk. METHODS: Ten-month-old infants with an
      older sibling with autism (n = 29, 16 females), and thus a genetic predisposition
      to developing the disorder themselves, were presented with white flashes on a
      computer monitor, and pupillary responses were captured using eye tracking. A
      control group matched on age and developmental level (n = 15, seven females) was
      also tested. RESULTS: The siblings of children with autism had a faster and
      stronger pupillary light reflex compared to control infants. Baseline pupil
      diameter was equal in the two groups, ruling out tonic autonomic imbalance as an
      explanation for these differences. CONCLUSIONS: This study establishes that
      infant siblings of children with autism have hypersensitive pupillary light
      reflexes, a result which supports the view that altered sensory processing in
      infancy is associated with elevated autism risk. Moreover, the study indicates
      that individual differences in autism susceptibility are linked to differences in
      the cholinergic system during an early developmental period.

PMID- 25750706
TI  - Identification of 2,4-diamino-6,7-dimethoxyquinoline derivatives as G9a
      inhibitors?Electronic supplementary information (ESI) available. See DOI:
      10.1039/c4md00274a.
AB  - G9a is a histone lysine methyltransferase (HKMT) involved in epigenetic
      regulation via the installation of histone methylation marks. 6,7
      Dimethoxyquinazoline analogues, such as BIX-01294, are established as potent,
      substrate competitive inhibitors of G9a. With an objective to identify novel
      chemotypes for substrate competitive inhibitors of G9a, we have designed and
      synthesised a range of heterocyclic scaffolds, and investigated their ability to
      inhibit G9a. These studies have led to improved understanding of the key
      pharmacophoric features of BIX-01294 and the identification of a new core
      quinoline inhibitory scaffold, which retains excellent potency and high
      selectivity. Molecular docking was carried out to explain the observed in vitro
      data.

PMID- 25750707
TI  - Criteria for selecting microhaplotypes: mixture detection and deconvolution.
AB  - BACKGROUND: DNA sequencing is likely to become a standard typing method in
      forensics in the near future. We define a microhaplotype to be a locus with two
      or more single nucleotide polymorphisms (SNPs) that occur within a short segment
      of DNA (e.g., 200 bp) that can be covered by a single sequence run and
      collectively define a multiallelic locus. Microhaplotypes can be highly
      informative for many forensic questions, including detection of mixtures of two
      or more sources in a DNA sample, a common problem in forensic practice. RESULTS:
      When all alleles are equally frequent, the probability of detecting three or more
      alleles in a mixture is at maximum. The classical population genetics concept of
      effective number of alleles at a locus, termed Ae, converts the unequal allele
      frequencies at a locus into a value that is equivalent to some number of equally
      frequent alleles, allowing microhaplotype loci to be ranked. The expectations for
      the ability to qualitatively detect mixtures are given for different integer
      values of Ae, and the cumulative probabilities of detecting mixtures based on
      testing multiple microhaps are shown to exceed 95% with as few as five loci with
      average Ae values of even slightly greater than 3.0. CONCLUSIONS: Microhaplotypes
      with Ae values of >3 will be exceedingly useful in ordinary forensic practice.
      Based on our studies, 3-SNP microhaplotypes will sometimes meet this criterion,
      but 4-SNP microhaplotypes can even exceed this criterion and have values >4.

PMID- 25750708
TI  - Focusing of mammalian cells under an ultrahigh pH gradient created by
      unidirectional electropulsation in a confined microchamber?Electronic
      supplementary information (ESI) available: Figures S1-S5 and videos S1-S2. See
      DOI: 10.1039/c4sc00319eClick here for additional data file.Click here for
      additional data file.Click here for additional data file.
AB  - The transport and manipulation of cells in microfluidic structures are often
      critically required in cellular analysis. Cells typically make consistent
      movement in a dc electric field in a single direction, due to their
      electrophoretic mobility or electroosmotic flow or the combination of the two.
      Here we demonstrate that mammalian cells focus to the middle of a closed
      microfluidic chamber under the application of unidirectional direct current
      pulses. With experimental and computational data, we show that under the pulses
      electrochemical reactions take place in the confined microscale space and create
      an ultrahigh and nonlinear pH gradient (~2 orders of magnitude higher than the
      ones in protein isoelectric focusing) at the middle of the chamber. The varying
      local pH affects the cell surface charge and the electrophoretic mobility,
      leading to focusing in free solution. Our approach provides a new and simple
      method for focusing and concentrating mammalian cells at the microscale.

PMID- 25750709
TI  - Expression of drug transporters in human kidney: impact of sex, age, and
      ethnicity.
AB  - BACKGROUND: Differences in expression of drug transporters in human kidney
      contribute to changes in pharmacokinetics and toxicokinetics of a variety of drug
      compounds. The basal expression levels of genes involved in drug transport
      processes in the kidney introduces differences in bioavailability, distribution,
      and clearance of drugs, possibly influencing drug efficacy and adverse reactions.
      Sex differences in gene expression of transporters are a key cause of differences
      in sex-dependent pharmacokinetics, which may characterize many drugs and
      contribute to individual differences in drug efficacy and toxicity. Therefore,
      evaluating the expression of drug transporters in normal human kidneys is
      important to better understand differences in drug bioavailability, distribution,
      and clearance of drugs in humans. Other factors such as age and ethnicity may
      also contribute to individual differences in gene expression of drug transporters
      in the human kidney. METHODS: Quantitative real-time PCR (QRT-PCR) was performed
      to determine the gene expression of 30 drug transporters in 95 age-matched normal
      human kidney tissues. Multiple Student's t-tests (Sidak-Bonferroni correction)
      and two-way ANOVA (Bonferroni correction) analyses were used to determine
      statistically significant differences. RESULTS: In the 30 transporter genes
      examined, sex, ethnicity, and age differences in gene expression were exhibited
      in normal human kidney tissue. These changes in expression were not found to be
      differentially significant. However, sex-age and sex-ethnicity interactions were
      found to be statistically significant. For sex-age interactions, SCL22A12 was
      found to be significantly higher expressed in females <50 years compared to males
      <50 years. Expression levels of SLC22A2, SLC22A12, SLC6A16, and ABCB6 were
      significantly higher in females <50 years compared to females >=50 years. In sex
      ethnicity interactions, expression levels of ATP7B and KCNJ8 were found to be
      significantly higher in African American females compared to European American
      females. Also, the expression of SLC31A2 was significantly higher in European
      American males compared to European American females. CONCLUSIONS: Sex, age, and
      ethnic differences impacted the expression of drug transporters in normal human
      kidneys, which suggests that the analysis of gene expression of drug transporters
      will aid in improving the usage/dosage of drug therapies influencing personalized
      medicine and susceptibility to adverse drug reactions.

PMID- 25750710
TI  - Life history correlates of fecal bacterial species richness in a wild population
      of the blue tit Cyanistes caeruleus.
AB  - Very little is known about the normal gastrointestinal flora of wild birds, or
      how it might affect or reflect the host's life-history traits. The aim of this
      study was to survey the species richness of bacteria in the feces of a wild
      population of blue tits Cyanistes caeruleus and to explore the relationships
      between bacterial species richness and various life-history traits, such as age,
      sex, and reproductive success. Using PCR-TGGE, 55 operational taxonomic units
      (OTUs) were identified in blue tit feces. DNA sequencing revealed that the 16S
      rRNA gene was amplified from a diverse range of bacteria, including those that
      shared closest homology with Bacillus licheniformis, Campylobacter lari,
      Pseudomonas spp., and Salmonella spp. For adults, there was a significant
      negative relationship between bacterial species richness and the likelihood of
      being detected alive the following breeding season; bacterial richness was
      consistent across years but declined through the breeding season; and breeding
      pairs had significantly more similar bacterial richness than expected by chance
      alone. Reduced adult survival was correlated with the presence of an OTU most
      closely resembling C. lari; enhanced adult survival was associated with an OTU
      most similar to Arthrobacter spp. For nestlings, there was no significant change
      in bacterial species richness between the first and second week after hatching,
      and nestlings sharing the same nest had significantly more similar bacterial
      richness. Collectively, these results provide compelling evidence that bacterial
      species richness was associated with several aspects of the life history of their
      hosts. 

PMID- 25750711
TI  - Plant diversity and identity effects on predatory nematodes and their prey.
AB  - There is considerable evidence that both plant diversity and plant identity can
      influence the level of predation and predator abundance aboveground. However, how
      the level of predation in the soil and the abundance of predatory soil fauna are
      related to plant diversity and identity remains largely unknown. In a
      biodiversity field experiment, we examined the effects of plant diversity and
      identity on the infectivity of entomopathogenic nematodes (EPNs, Heterorhabditis
      and Steinernema spp.), which prey on soil arthropods, and abundance of
      carnivorous non-EPNs, which are predators of other nematode groups. To obtain a
      comprehensive view of the potential prey/food availability, we also quantified
      the abundance of soil insects and nonpredatory nematodes and the root biomass in
      the experimental plots. We used structural equation modeling (SEM) to investigate
      possible pathways by which plant diversity and identity may affect EPN
      infectivity and the abundance of carnivorous non-EPNs. Heterorhabditis spp.
      infectivity and the abundance of carnivorous non-EPNs were not directly related
      to plant diversity or the proportion of legumes, grasses and forbs in the plant
      community. However, Steinernema spp. infectivity was higher in monocultures of
      Festuca rubra and Trifolium pratense than in monocultures of the other six plant
      species. SEM revealed that legumes positively affected Steinernema infectivity,
      whereas plant diversity indirectly affected the infectivity of
      HeterorhabditisEPNs via effects on the abundance of soil insects. The abundance
      of prey (soil insects and root-feeding, bacterivorous, and fungivorous nematodes)
      increased with higher plant diversity. The abundance of prey nematodes was also
      positively affected by legumes. These plant community effects could not be
      explained by changes in root biomass. Our results show that plant diversity and
      identity effects on belowground biota (particularly soil nematode community) can
      differ between organisms that belong to the same feeding guild and that
      generalizations about plant diversity effects on soil organisms should be made
      with great caution. 

PMID- 25750712
TI  - Transcriptomics of two evolutionary novelties: how to make a sperm-transfer organ
      out of an anal fin and a sexually selected "sword" out of a caudal fin.
AB  - Swords are exaggerated male ornaments of swordtail fishes that have been of great
      interest to evolutionary biologists ever since Darwin described them in the
      Descent of Man (1871). They are a novel sexually selected trait derived from
      modified ventral caudal fin rays and are only found in the genus Xiphophorus.
      Another phylogenetically more widespread and older male trait is the gonopodium,
      an intromittent organ found in all poeciliid fishes, that is derived from a
      modified anal fin. Despite many evolutionary and behavioral studies on both
      traits, little is known so far about the molecular mechanisms underlying their
      development. By investigating transcriptomic changes (utilizing a RNA-Seq
      approach) in response to testosterone treatment in the swordtail fish,
      Xiphophorus hellerii, we aimed to better understand the architecture of the gene
      regulatory networks underpinning the development of these two evolutionary
      novelties. Large numbers of genes with tissue-specific expression patterns were
      identified. Among the "sword genes" those involved in embryonic organ
      development, sexual character development and coloration were highly expressed,
      while in the gonopodium rather more morphogenesis-related genes were found.
      Interestingly, many genes and genetic pathways are shared between both developing
      novel traits derived from median fins: the sword and the gonopodium. Our analyses
      show that a larger set of gene networks was co-opted during the development and
      evolution of the "older" gonopodium than in the "younger," and morphologically
      less complex trait, the sword. We provide a catalog of candidate genes for future
      efforts to dissect the development of those sexually selected exaggerated male
      traits in swordtails. 

PMID- 25750713
TI  - Metacommunity and phylogenetic structure determine wildlife and zoonotic
      infectious disease patterns in time and space.
AB  - The potential for disease transmission at the interface of wildlife, domestic
      animals and humans has become a major concern for public health and conservation
      biology. Research in this subject is commonly conducted at local scales while the
      regional context is neglected. We argue that prevalence of infection at local and
      regional levels is influenced by three mechanisms occurring at the landscape
      level in a metacommunity context. First, (1) dispersal, colonization, and
      extinction of pathogens, reservoir or vector hosts, and nonreservoir hosts, may
      be due to stochastic and niche-based processes, thus determining distribution of
      all species, and then their potential interactions, across local communities
      (metacommunity structure). Second, (2) anthropogenic processes may drive
      environmental filtering of hosts, nonhosts, and pathogens. Finally, (3)
      phylogenetic diversity relative to reservoir or vector host(s), within and
      between local communities may facilitate pathogen persistence and circulation.
      Using a metacommunity approach, public heath scientists may better evaluate the
      factors that predispose certain times and places for the origin and emergence of
      infectious diseases. The multidisciplinary approach we describe fits within a
      comprehensive One Health and Ecohealth framework addressing zoonotic infectious
      disease outbreaks and their relationship to their hosts, other animals, humans,
      and the environment. 

PMID- 25750714
TI  - Saturating light and not increased carbon dioxide under ocean acidification
      drives photosynthesis and growth in Ulva rigida (Chlorophyta).
AB  - Carbon physiology of a genetically identified Ulva rigida was investigated under
      different CO2(aq) and light levels. The study was designed to answer whether (1)
      light or exogenous inorganic carbon (Ci) pool is driving growth; and (2) elevated
      CO2(aq) concentration under ocean acidification (OA) will downregulate CAext
      mediated [Formula: see text] dehydration and alter the stable carbon isotope
      (delta (13)C) signatures toward more CO2 use to support higher growth rate. At
      pHT 9.0 where CO2(aq) is <1 MUmol L(-1), inhibition of the known [Formula: see
      text] use mechanisms, that is, direct [Formula: see text] uptake through the AE
      port and CAext-mediated [Formula: see text] dehydration decreased net
      photosynthesis (NPS) by only 56-83%, leaving the carbon uptake mechanism for the
      remaining 17-44% of the NPS unaccounted. An in silico search for carbon
      concentrating mechanism elements in expressed sequence tag libraries of Ulva
      found putative light-dependent [Formula: see text] transporters to which the
      remaining NPS can be attributed. The shift in delta (13)C signatures from -220/00
      toward -100/00 under saturating light but not under elevated CO2(aq) suggest
      preference and substantial [Formula: see text] use to support photosynthesis and
      growth. U. rigida is Ci saturated, and growth was primarily controlled by light.
      Therefore, increased levels of CO2(aq) predicted for the future will not, in
      isolation, stimulate Ulva blooms. 

PMID- 25750715
TI  - Phylogenetic and morphological relationships between nonvolant small mammals
      reveal assembly processes at different spatial scales.
AB  - The relative roles of historical processes, environmental filtering, and
      ecological interactions in the organization of species assemblages vary depending
      on the spatial scale. We evaluated the phylogenetic and morphological
      relationships between species and individuals (i.e., inter- and intraspecific
      variability) of Neotropical nonvolant small mammals coexisting in grassland
      forest ecotones, in landscapes and in regions, that is, three different scales.
      We used a phylogenetic tree to infer evolutionary relationships, and
      morphological traits as indicators of performance and niche similarities between
      species and individuals. Subsequently, we applied phylogenetic and morphologic
      indexes of diversity and distance between species to evaluate small mammal
      assemblage structures on the three scales. The results indicated a repulsion
      pattern near forest edges, showing that phylogenetically similar species
      coexisted less often than expected by chance. The strategies for niche
      differentiation might explain the phylogenetic repulsion observed at the edge.
      Phylogenetic and morphological clustering in the grassland and at the forest
      interior indicated the coexistence of closely related and ecologically similar
      species and individuals. Coexistence patterns were similar whether species-trait
      values or individual values were used. At the landscape and regional scales,
      assemblages showed a predominant pattern of phylogenetic and morphological
      clustering. Environmental filters influenced the coexistence patterns at three
      scales, showing the importance of phylogenetically conserved ecological
      tolerances in enabling taxa co-occurrence. Evidence of phylogenetic repulsion in
      one region indicated that other processes beyond environmental filtering are
      important for community assembly at broad scales. Finally, ecological
      interactions and environmental filtering seemed important at the local scale,
      while environmental filtering and historical colonization seemed important for
      community assembly at broader scales. 

PMID- 25750716
TI  - Structure and diversity of phyllostomid bat assemblages on riparian corridors in
      a human-dominated tropical landscape.
AB  - Tropical forests around the world have been lost, mainly because of agricultural
      activities. Linear elements like riparian vegetation in fragmented tropical
      landscapes help maintain the native flora and fauna. Information about the role
      of riparian corridors as a reservoir of bat species, however, is scanty. We
      assessed the value of riparian corridors on the conservation of phyllostomid bat
      assemblage in an agricultural landscape of southern Mexico. For 2 years (2011
      2013), mist-netting at ground level was carried out twice during the dry season
      (December to May) and twice during the wet season (June to November) in different
      habitats: (1) riparian corridors in mature forest, (2) riparian corridors in
      pasture, (3) continuous forest away from riparian vegetation, and (4) open
      pastures. Each habitat was replicated three times. To determine the influence of
      vegetation structure on bat assemblages, all trees (>=10 cm dbh) were sampled in
      all habitats. Overall, 1752 individuals belonging to 28 species of Phyllostomidae
      were captured with Sternodermatinae being the most rich and abundant subfamily.
      Riparian corridors in mature forest and pastures had the greatest species
      richness and shared 65% of all species. Open pastures had the lowest richness and
      abundance of bats with no Phyllostominae species recorded. Six of the 18 species
      recorded could be considered as habitat indicators. There was a positive
      relationship between bat species composition and tree basal area. Our findings
      suggest that contrary to our expectations, bats with generalist habits and
      naturally abundant could be useful detector taxa of habitat modification, rather
      than bats strongly associated with undisturbed forest. Also in human-dominated
      landscapes, the maintenance of habitat elements such as large trees in riparian
      corridors can serve as reservoirs for bat species, especially for those that are
      strongly associated with undisturbed forest. 

PMID- 25750717
TI  - Sexually selected UV signals in the tropical ornate jumping spider, Cosmophasis
      umbratica may incur costs from predation.
AB  - Sexually selected ornaments and signals are costly to maintain if they are
      maladaptive in nonreproductive contexts. The jumping spider Cosmophasis umbratica
      exhibits distinct sexual dichromatism with males displaying elaborate UV body
      markings that signal male quality. Female C. umbratica respond favorably to UV
      reflecting males and ignore males that have their UV masked. However, Portia
      labiata, a UV-sensitive spider-eating specialist and a natural predator of C.
      umbratica, is known to use UV reflectance as a cue when hunting prey. We
      investigated the cost of these UV signals in C. umbratica in terms of their
      predation risk. Under experimental conditions, three choice scenarios were
      presented to P. labiata individuals. Choices by P. labiata were made between male
      C. umbratica with and without the UV signal; a UV-reflecting male and non-UV
      reflecting female; and a UV-masked male and female. The presence and absence of
      UV signals was manipulated using an optical filter. Portia labiata exhibited a
      strong bias toward UV+ individuals. These results suggest the sexually selected
      trait of UV reflectance increases the visibility of males to UV-sensitive
      predators. The extent of this male-specific UV signal then is potentially
      moderated by predation pressure. Interestingly though, P. labiata still preferred
      males to females irrespective of whether UV reflectance was present or not. This
      suggests P. labiata can switch cues when conditions to detect UV reflectance are
      not optimal. 

PMID- 25750718
TI  - Limnological regime shifts caused by climate warming and Lesser Snow Goose
      population expansion in the western Hudson Bay Lowlands (Manitoba, Canada).
AB  - Shallow lakes are dominant features in subarctic and Arctic landscapes and are
      responsive to multiple stressors, which can lead to rapid changes in limnological
      regimes with consequences for aquatic resources. We address this theme in the
      coastal tundra region of Wapusk National Park, western Hudson Bay Lowlands
      (Canada), where climate has warmed during the past century and the Lesser Snow
      Goose (LSG; Chen caerulescens caerulescens) population has grown rapidly during
      the past ?40 years. Integration of limnological and paleolimnological analyses
      documents profound responses of productivity, nutrient cycling, and aquatic
      habitat to warming at three ponds ("WAP 12", "WAP 20", and "WAP 21"), and to LSG
      disturbance at the two ponds located in an active nesting area (WAP 20, WAP 21).
      Based on multiparameter analysis of (210)Pb-dated sediment records from all three
      ponds, a regime shift occurred between 1875 and 1900 CE marked by a transition
      from low productivity, turbid, and nutrient-poor conditions of the Little Ice Age
      to conditions of higher productivity, lower nitrogen availability, and the
      development of benthic biofilm habitat as a result of climate warming. Beginning
      in the mid-1970s, sediment records from WAP 20 and WAP 21 reveal a second regime
      shift characterized by accelerated productivity and increased nitrogen
      availability. Coupled with 3 years of limnological data, results suggest that
      increased productivity at WAP 20 and WAP 21 led to atmospheric CO2 invasion to
      meet algal photosynthetic demand. This limnological regime shift is attributed to
      an increase in the supply of catchment-derived nutrients from the arrival of LSG
      and their subsequent disturbance to the landscape. Collectively, findings
      discriminate the consequences of warming and LSG disturbance on tundra ponds from
      which we identify a suite of sensitive limnological and paleolimnological
      measures that can be utilized to inform aquatic ecosystem monitoring. 

PMID- 25750719
TI  - On the analysis of phylogenetically paired designs.
AB  - As phylogenetically controlled experimental designs become increasingly common in
      ecology, the need arises for a standardized statistical treatment of these
      datasets. Phylogenetically paired designs circumvent the need for resolved
      phylogenies and have been used to compare species groups, particularly in the
      areas of invasion biology and adaptation. Despite the widespread use of this
      approach, the statistical analysis of paired designs has not been critically
      evaluated. We propose a mixed model approach that includes random effects for
      pair and species. These random effects introduce a "two-layer" compound symmetry
      variance structure that captures both the correlations between observations on
      related species within a pair as well as the correlations between the repeated
      measurements within species. We conducted a simulation study to assess the effect
      of model misspecification on Type I and II error rates. We also provide an
      illustrative example with data containing taxonomically similar species and
      several outcome variables of interest. We found that a mixed model with species
      and pair as random effects performed better in these phylogenetically explicit
      simulations than two commonly used reference models (no or single random effect)
      by optimizing Type I error rates and power. The proposed mixed model produces
      acceptable Type I and II error rates despite the absence of a phylogenetic tree.
      This design can be generalized to a variety of datasets to analyze repeated
      measurements in clusters of related subjects/species. 

PMID- 25750720
TI  - Interactions with successional stage and nutrient status determines the life-form
      specific effects of increased soil temperature on boreal forest floor vegetation.
AB  - The boreal forest is one of the largest terrestrial biomes and plays a key role
      for the global carbon balance and climate. The forest floor vegetation has a
      strong influence on the carbon and nitrogen cycles of the forests and is
      sensitive to changes in temperature conditions and nutrient availability.
      Additionally, the effects of climate warming on forest floor vegetation have been
      suggested to be moderated by the tree layer. Data on the effects of soil warming
      on forest floor vegetation from the boreal forest are, however, very scarce. We
      studied the effects on the forest floor vegetation in a long-term (18 years) soil
      warming and fertilization experiment in a Norway spruce stand in northern Sweden.
      During the first 9 years, warming favored early successional species such as
      grasses and forbs at the expense of dwarf shrubs and bryophytes in unfertilized
      stands, while the effects were smaller after fertilization. Hence, warming led to
      significant changes in species composition and an increase in species richness in
      the open canopy nutrient limited forest. After another 9 years of warming and
      increasing tree canopy closure, most of the initial effects had ceased,
      indicating an interaction between forest succession and warming. The only
      remaining effect of warming was on the abundance of bryophytes, which contrary to
      the initial phase was strongly favored by warming. We propose that the suggested
      moderating effects of the tree layer are specific to plant life-form and conclude
      that the successional phase of the forest may have a considerable impact on the
      effects of climate change on forest floor vegetation and its feedback effects on
      the carbon and nitrogen cycles, and thus on the climate. 

PMID- 25750721
TI  - Parasitism and the expression of sexual dimorphism.
AB  - Although a negative covariance between parasite load and sexually selected trait
      expression is a requirement of few sexual selection models, such a covariance may
      be a general result of life-history allocation trade-offs. If both allocation to
      sexually selected traits and to somatic maintenance (immunocompetence) are
      condition dependent, then in populations where individuals vary in condition, a
      positive covariance between trait expression and immunocompetence, and thus a
      negative covariance between trait and parasite load, is expected. We test the
      prediction that parasite load is generally related to the expression of sexual
      dimorphism across two breeding seasons in a wild salamander population and show
      that males have higher trematode parasite loads for their body size than females
      and that a key sexually selected trait covaries negatively with parasite load in
      males. We found evidence of a weaker negative relationship between the analogous
      female trait and parasite infection. These results underscore that parasite
      infection may covary with expression of sexually selected traits, both within and
      among species, regardless of the model of sexual selection, and also suggest that
      the evolution of condition dependence in males may affect the evolution of female
      trait expression. 

PMID- 25750722
TI  - Temperature and zooplankton size structure: climate control and basin-scale
      comparison in the North Pacific.
AB  - The global distribution of zooplankton community structure is known to follow
      latitudinal temperature gradients: larger species in cooler, higher latitudinal
      regions. However, interspecific relationships between temperature and size in
      zooplankton communities have not been fully examined in terms of temporal
      variation. To re-examine the relationship on a temporal scale and the effects of
      climate control thereon, we investigated the variation in copepod size structure
      in the eastern and western subarctic North Pacific in 2000-2011. This report
      presents the first basin-scale comparison of zooplankton community changes in the
      North Pacific based on a fully standardized data set obtained from the Continuous
      Plankton Recorder (CPR) survey. We found an increase in copepod community size
      (CCS) after 2006-2007 in the both regions because of the increased dominance of
      large cold-water species. Sea surface temperature varied in an east-west dipole
      manner, showing the typical Pacific Decadal Oscillation pattern: cooling in the
      east and warming in the west after 2006-2007. The observed positive correlation
      between CCS and sea surface temperature in the western North Pacific was
      inconsistent with the conventional interspecific temperature-size relationship.
      We explained this discrepancy by the geographical shift of the upper boundary of
      the thermal niche, the 9 degrees C isotherm, of large cold-water species. In the
      eastern North Pacific, the boundary stretched northeast, to cover a large part of
      the sampling area after 2006-2007. In contrast, in the western North Pacific, the
      isotherm location hardly changed and the sampling area remained within its
      thermal niche throughout the study period, despite the warming that occurred. Our
      study suggests that while a climate-induced basin-scale cool-warm cycle can alter
      copepod community size and might subsequently impact the functions of the marine
      ecosystem in the North Pacific, the interspecific temperature-size relationship
      is not invariant and that understanding region-specific processes linking climate
      and ecosystem is indispensable. 

PMID- 25750723
TI  - No evidence that within-group male relatedness reduces harm to females in
      Drosophila.
AB  - Conflict between males and females over whether, when, and how often to mate
      often leads to the evolution of sexually antagonistic interactions that reduce
      female reproductive success. Because the offspring of relatives contribute to
      inclusive fitness, high relatedness between rival males might be expected to
      reduce competition and result in the evolution of reduced harm to females. A
      recent study investigated this possibility in Drosophila melanogaster and
      concluded that groups of brothers cause less harm to females than groups of
      unrelated males, attributing the effect to kin selection. That study did not
      control for the rearing environment of males, rendering the results impossible to
      interpret in the context of kin selection. Here, we conducted a similar
      experiment while manipulating whether males developed with kin prior to being
      placed with females. We found no difference between related and unrelated males
      in the harm caused to females when males were reared separately. In contrast,
      when related males developed and emerged together before the experiment, female
      reproductive output was higher. Our results show that relatedness among males is
      insufficient to reduce harm to females, while a shared rearing environment -
      resulting in males similar to or familiar with one another - is necessary to
      generate this pattern. 

PMID- 25750724
TI  - Genetic structure and historical demography of Schizothorax nukiangensis
      (Cyprinidae) in continuous habitat.
AB  - Geographic distance, different living habitats or Pleistocene climatic
      oscillations have frequently been found to shape population genetic structure in
      many species. The genetic structure of Schizothorax nukiangensis, a high
      altitude, valuable fish species, which is distributed throughout the Nujiang
      River, was investigated by mitochondrial DNA sequence analysis. The cytochrome c
      oxidase subunit I (COI), cytochrome b (cytb), and the mitochondrial control
      region (MCR) of S. nukiangensis were concatenated for examination of population
      structure and demographic history. The concatenated data set (2405 bp) implied a
      pronounced genetic population structure (overall F ST = 0.149) and defined two
      population units. Strong differentiation was detected between the Sanjiangkou
      (SJK) population and other populations due to environmental heterogeneity,
      dispersal ability, and/or glacial cycles. Additional DNA sequencing of the
      nuclear RAG2 gene also examined significant differentiation between two units and
      between SJK and the upstream populations (U-unit). Recent expansion events
      suggest that S. nukiangensis may have undergone a rapid increase during warm
      interglacial periods. Surprisingly, S. nukiangensis appears to have undergone an
      obvious expansion during the last glaciations (LG) for cold hardiness and a sharp
      contraction from 1.5 ka to the present. However, two population units exhibited
      different reflections during the LG, which might be closely related to their
      living habitats and cold hardiness. A clear pattern of isolation by distance was
      detected in S. nukiangensis due to feeding habits, limited dispersal ability,
      and/or philopatry. It is vitally important that more attention be given to S.
      nukiangensis due to low genetic diversity, lack of gene flow, and recent
      population contraction. 

PMID- 25750726
TI  - Synthesis of a 2,4,6,8,10-dodecapentanoic acid thioester as a substrate for
      biosynthesis of Heat Stable Antifungal Factor (HSAF).
AB  - The N-acetylcystamine (SNAC) thioester of dodecapentaenoic acid, an analog of a
      putative intermediate in the biosynthesis of Heat Stable Antifungal Factor
      (HSAF), is synthesized. Key steps include sequential Horner-Emmons homologations
      with the Weinreb amide of diethylphosponoacetic acid, and thioesterification of
      an aldol-derived 3-hydroxyalkanoate, which serves as a stable precursor of the
      sensitive polyenoate. The thioester was investigated as a biosynthetic substrate
      using a purified nonribosomal peptide synthetase and was not incorporated in the
      observed products.

PMID- 25750727
TI  - The surgical admissions proforma: Does it make a difference?
AB  - Admissions records are essential in communicating key information regarding
      unwell patients and at handover of care. We designed, implemented and evaluated
      the impact of a standardised surgical clerking proforma on documentation and
      clinician acceptability in comparison to freehand clerking. A clerking proforma
      was implemented for all acute general surgical admissions. Documentation was
      assessed according to 32 criteria based on the Royal College of Surgeons of
      England guidelines, for admissions before (n = 72) and after (n = 96)
      implementation. Fisher's exact test and regression analysis were used to compare
      groups. Surgical team members were surveyed regarding attitudes towards the new
      proforma. Proforma uptake was 73%. After implementation, documentation increased
      in 28/32 criteria. This was statistically significant in 17 criteria, including
      past surgical history (p < 0.01), medication history (p = 0.03), ADLs (p = 0.02),
      systems review (p < 0.01), blood pressure (p < 0.01), blood results (p = 0.02)
      and advice given to the patient (p = 0.02). The proforma remained beneficial
      after regression analysis accounted for differences in time of day, seniority of
      the doctor and nights or weekends (coefficient = 0.12 [p < 0.01]). 89% of the
      surgical team felt the form improved quality of documentation and preferred its
      use to freehand clerking. 94% felt it was beneficial on the post-take ward-round.
      Audit quality control was also more reliable with the proforma (inter-observer
      agreement = 99.3% [kappa = 0.997]) versus freehand clerking (97.1% [kappa =
      0.941]). Our study demonstrates that a standardised surgical clerking proformas
      improves the quantity and quality of documentation in comparison to freehand
      clerking, is preferred by health professionals and improves reliability of the
      audit quality control process. 

PMID- 25750728
TI  - Gluteal Compartment Syndrome following bariatric surgery: A rare but important
      complication.
AB  - Gluteal Compartment Syndrome is a rare condition caused by excessive pressure
      within the gluteal compartments which leads to a number of potentially serious
      sequelae including rhabdomyolysis, nerve damage, renal failure and death. As
      bariatric patients are heavy and during prolonged bariatric procedures lie in one
      position for extended periods of time, they are especially susceptible to
      developing this complication. It is therefore essential that bariatric surgeons
      are aware of this complication and how to minimise the chances of it occurring
      and how to diagnose it. We describe a case of Gluteal Compartment Syndrome in a
      patient following a gastric bypass and review the aetiology, pathophysiology,
      treatment and prevention of this complication. 

PMID- 25750729
TI  - Public attitudes toward immigration in turbulent times.

PMID- 25750730
TI  - New focus of Kyasanur Forest disease virus activity in a tribal area in Kerala,
      India, 2014.
AB  - BACKGROUND: Kyasanur Forest disease (KFD) is a febrile illness characterized by
      hemorrhages, and is reported endemic in the Shimoga district in Karnataka state,
      India. It is caused by the KFD virus (KFDV) of the family Flaviviridae, and is
      transmitted to monkeys and humans by Haemaphysalis ticks. FINDINGS: We
      investigated a new focus of KFD among tribals in a reserve forest in Kerala
      state, India. A suspected case was defined as a person presenting with acute
      fever, headache, or myalgia. Human sera were collected and tested for KFDV RNA by
      real-time RT-PCR, RT-nPCR assay, and anti-KFDV IgM and IgG by ELISA. The index
      case was a tribal woman with febrile illness, severe myalgia, gum bleeding, and
      hematemesis. Anti-KFDV IgM antibody was detected in acute and convalescent sera
      of the index case along with IgG in the second serum. None of her family members
      reported fever. On verbal autopsy, two more fatal cases were identified as
      probable primary cases. Acute serum from a case in the second cluster was
      detected positive for KFDV RNA by real time RT-PCR (Ct = 32) and RT-nPCR.
      Sequences of E gene showed highest similarity of 98.0% with the KFDV W-377
      isolate nucleotide and 100% identity with amino acid. Anti-KFDV IgM was detected
      in the serum of one family member of the index case, as well as in one out of 17
      other tribals. CONCLUSIONS: We confirmed a new focus of KFDV activity among
      tribals in a reserve forest in the Malappuram district of Kerala, India.

PMID- 25750731
TI  - The phosphoinositide 3-kinase pathway and therapy resistance in cancer.
AB  - The phosphoinositide 3-kinase (PI3K)/Akt/mechanistic target of rapamycin (mTOR)
      signaling network is a master regulator of processes that contribute to
      tumorigenesis and tumor maintenance. The PI3K pathway also plays a critical role
      in driving resistance to diverse anti-cancer therapies. This review article
      focuses on mechanisms by which the PI3K pathway contributes to therapy resistance
      in cancer, and highlights potential combination therapy strategies to circumvent
      resistance driven by PI3K signaling. In addition, resistance mechanisms that
      limit the clinical efficacy of small molecule inhibitors of the PI3K pathway are
      discussed. 

PMID- 25750732
TI  - Structure and mechanism of ABC transporters.
AB  - All living organisms depend on primary and secondary membrane transport for the
      supply of external nutrients and removal or sequestration of unwanted (toxic)
      compounds. Due to the chemical diversity of cellular molecules, it comes as no
      surprise that a significant part of the proteome is dedicated to the active
      transport of cargo across the plasma membrane or the membranes of subcellular
      organelles. Transport against a chemical gradient can be driven by, for example,
      the free energy change associated with ATP hydrolysis (primary transport), or
      facilitated by the potential energy of the chemical gradient of another molecule
      (secondary transport). Primary transporters include the rotary motor ATPases (F-,
      A-, and V-ATPases), P-type ATPases and a large family of integral membrane
      proteins referred to as "ABC" (ATP binding cassette) transporters. ABC
      transporters are widespread in all forms of life and are characterized by two
      nucleotide-binding domains (NBD) and two transmembrane domains (TMDs). ATP
      hydrolysis on the NBD drives conformational changes in the TMD, resulting in
      alternating access from inside and outside of the cell for unidirectional
      transport across the lipid bilayer. Common to all ABC transporters is a signature
      sequence or motif, LSGGQ, that is involved in nucleotide binding. Both importing
      and exporting ABC transporters are found in bacteria, whereas the majority of
      eukaryotic family members function in the direction of export. Recent progress
      with the X-ray crystal structure determination of a variety of bacterial and
      eukaryotic ABC transporters has helped to advance our understanding of the ATP
      hydrolysis-driven transport mechanism but has also illustrated the large
      structural and functional diversity within the family. 

PMID- 25750733
TI  - Holding the inflammatory system in check: NLRs keep it cool.
AB  - Inflammation is a double-edged sword. While short-lived, acute inflammation is
      essential for the repair and resolution of infection and damage, uncontrolled and
      unresolved chronic inflammation is central to several diseases, including cancer,
      autoimmune diseases, allergy, metabolic disease, and cardiovascular disease. This
      report aims to review the literature regarding several members of the nucleotide
      binding domain, leucine-rich repeat-containing receptor (NLR) family of pattern
      recognition sensors/receptors that serve as checkpoints for inflammation.
      Understanding the negative regulation of inflammation is highly relevant to the
      development of therapeutics for inflammatory as well as infectious diseases. 

PMID- 25750734
TI  - Potential mechanisms to explain how LABAs and PDE4 inhibitors enhance the
      clinical efficacy of glucocorticoids in inflammatory lung diseases.
AB  - Inhaled glucocorticoids acting via the glucocorticoid receptor are a mainstay
      treatment option for individuals with asthma. There is a consensus that the
      remedial actions of inhaled glucocorticoids are due to their ability to suppress
      inflammation by modulating gene expression. While inhaled glucocorticoids are
      generally effective in asthma, there are subjects with moderate-to-severe disease
      in whom inhaled glucocorticoids fail to provide adequate control. For these
      individuals, asthma guidelines recommend that a long-acting beta2-adrenoceptor
      agonist (LABA) be administered concurrently with an inhaled glucocorticoid. This
      so-called "combination therapy" is often effective and clinically superior to the
      inhaled glucocorticoid alone, irrespective of dose. LABAs, and another class of
      drug known as phosphodiesterase 4 (PDE4) inhibitors, may also enhance the
      efficacy of inhaled glucocorticoids in chronic obstructive pulmonary disease
      (COPD). In both conditions, these drugs are believed to work by elevating the
      concentration of cyclic adenosine-3',5'-monophosphate (cAMP) in target cells and
      tissues. Despite the success of inhaled glucocorticoid/LABA combination therapy,
      it remains unclear how an increase in cAMP enhances the clinical efficacy of an
      inhaled glucocorticoid. In this report, we provide a state-of-the-art appraisal,
      including unresolved and controversial issues, of how cAMP-elevating drugs and
      inhaled glucocorticoids interact at a molecular level to deliver enhanced anti
      inflammatory benefit over inhaled glucocorticoid monotherapy. We also speculate
      on ways to further exploit this desirable interaction. Critical discussion of how
      these two drug classes regulate gene transcription, often in a synergistic
      manner, is a particular focus. Indeed, because interplay between glucocorticoid
      receptor and cAMP signaling pathways may contribute to the superiority of inhaled
      glucocorticoid/LABA combination therapy, understanding this interaction may
      provide a logical framework to rationally design these multicomponent
      therapeutics that was not previously possible. 

PMID- 25750735
TI  - Solving the puzzle of autoimmunity: critical questions.
AB  - Despite recent advances in delineating the pathogenic mechanisms of autoimmune
      disease, the puzzle that reveals the true picture of these diverse immunological
      disorders is yet to be solved. We know that the human leukocyte antigen (HLA)
      loci as well as many different genetic susceptibility loci with relatively small
      effect sizes predispose to various autoimmune diseases and that environmental
      factors are involved in triggering disease. Models for mechanisms of disease
      become increasingly complex as relationships between components of both the
      adaptive and innate immune systems are untangled at the molecular level. In this
      article, we pose some of the important questions about autoimmunity where the
      answers will advance our understanding of disease pathogenesis and improve the
      rational design of novel therapies. How is autoimmunity triggered, and what
      components of the immune response drive the clinical manifestations of disease?
      What determines whether a genetically predisposed individual will develop an
      autoimmune disease? Is restoring immune tolerance the secret to finding cures for
      autoimmune disease? Current research efforts seek answers to these big questions.

PMID- 25750736
TI  - Autophagy in cancer.
AB  - Autophagy is a catabolic degradation process in which cellular proteins and
      organelles are engulfed by double-membrane autophagosomes and degraded in
      lysosomes. Autophagy has emerged as a critical pathway in tumor development and
      cancer therapy, although its precise function remains a conundrum. The current
      consensus is that autophagy has a dual role in cancer. On the one hand, autophagy
      functions as a tumor suppressor mechanism by preventing the accumulation of
      damaged organelles and aggregated proteins. On the other hand, autophagy is a key
      cell survival mechanism for established tumors; therefore autophagy inhibition
      suppresses tumor progression. Here, we summarize recent progress on the role of
      autophagy in tumorigenesis and cancer therapy. 

PMID- 25750737
TI  - New tangles in the auxin signaling web.
AB  - Plants use auxin to relay critical information that shapes their growth and
      development. Auxin perception and transcriptional activation are mediated by the
      degradation of Aux/IAA repressor proteins. Degradation of Aux/IAAs relieves
      repression on Auxin Response Factors (ARFs), which bind DNA sequences called
      Auxin Response Elements (AuxREs). In most higher plant genomes, multiple paralogs
      exist for each part of the auxin nuclear signaling pathway. This potential
      combinatorial diversity in signaling pathways likely contributes to the myriad of
      context-specific responses to auxin. Recent structures of several domains from
      ARF proteins have exposed new modes of ARF dimerization, new models for ARF-AuxRE
      specificity, and the strong likelihood of larger order complexes formed by ARF
      and Aux/IAA homo- and heteromultimerization. Preliminary experiments support a
      role for these novel interactions in planta, further increasing the potential
      architectural complexity of this seemingly simple pathway. 

PMID- 25750738
TI  - Sublingual thyroid ectopy: similarities and differences with Kallmann syndrome.
AB  - Permanent primary congenital hypothyroidism (CH), the commonest cause of
      preventable intellectual disability, is due to defects in the embryonic
      development of the thyroid in the vast majority of cases. These defects are
      collectively called thyroid dysgenesis. The thyroid may be absent (athyreosis)
      but, more commonly, a sublingual thyroid ectopy without lateral lobes, is the
      only thyroid tissue present. Such an ectopy presumably results from an arrest in
      the downward migration of the median anlage. Thyroid ectopy almost always occurs
      in a sporadic fashion. However, first-degree relatives are affected more often
      than chance alone would predict. On the other hand, almost all reported
      monozygotic twin pairs are discordant for thyroid ectopy. Current research is
      aimed at reconciling these contradictory epidemiological data. We propose a two
      hit mechanism associating a germline predisposing factor with another genetic or
      epigenetic alteration within the ectopic thyroid tissue itself or, as in some
      forms of Kallmann syndrome, in the structures surrounding the thyroid during
      embryogenesis. Thyroid ectopy, a model for sporadic congenital malformations in
      humans, is also associated with congenital heart disease, and molecular
      mechanisms common to thyroid and heart development are being unraveled. 

PMID- 25750739
TI  - Empiric/pre-emptive anti-Candida therapy in non-neutropenic ICU patients.
AB  - The potential of the systemic antifungal treatment of non-immunocompromised
      patients with sepsis, extra-digestive Candida colonization and multiple organ
      failure is unknown, although it represents three out of four antifungal
      treatments prescribed in intensive care units. It may allow an early treatment of
      invasive fungal infection at incubation phase, but exposes patients to
      unnecessary antifungal treatments with subsequent costs and antifungal selection
      pressure. As early diagnostic tests for invasive candidiasis are still considered
      insufficient, the potential of this strategy needs to be demonstrated by a
      randomized controlled trial. Such a trial is currently ongoing. 

PMID- 25750740
TI  - Treatment of distant metastases from follicular cell-derived thyroid cancer.
AB  - Distant metastases from thyroid cancer of follicular origin are uncommon.
      Treatment includes levothyroxine administration at suppressive doses, focal
      treatment modalities with surgery, external radiation therapy and thermal
      ablation, and radioiodine in patients with uptake of (131)I in their metastases.
      Two thirds of distant metastases will become refractory to radioiodine at some
      point, and when there is a significant tumor burden and documented progression on
      imaging, a treatment with a kinase inhibitor may provide benefits. 

PMID- 25750741
TI  - Root hair growth: it's a one way street.
AB  - Over the last few decades, our understanding of directed cell growth in different
      organisms has substantially improved. Tip-growing cells in plants elongate
      rapidly via targeted deposition of cell wall and membrane material at the cell
      apex, and use turgor pressure as a driving force for expansion. This type of
      polar growth requires a high degree of coordination between a plethora of
      cellular and extracellular components and compounds, including calcium dynamics,
      apoplastic reactive oxygen species and pH, the cytoskeleton, and vesicular
      trafficking. In this review, we attempt to outline and summarize the factors that
      control root hair growth and how they work together as a team. 

PMID- 25750742
TI  - Recent advances in the diagnosis and management of pre-eclampsia.
AB  - Pre-eclampsia complicates around 5% of pregnancies and hypertensive disorders of
      pregnancy are responsible for over 60,000 maternal deaths worldwide annually. Pre
      eclampsia is characterized by hypertension and features of multiple organ
      disease. Diagnosis remains a challenge as clinical presentation is highly
      variable and even with severe disease a woman can be asymptomatic. Pre-eclampsia
      is characterized by abnormal placentation with subsequent maternal inflammatory
      and vascular response. Improved understanding of the underlying pathophysiology
      relating to the role of angiogenic factors, has emerged and placed intense
      interest on their role in prognostic modelling or diagnosis of pre-eclampsia.
      This article summarizes new developments in diagnosis with a focus on angiogenic
      biomarkers for prediction of disease onset, and recent advances in management
      strategies for patients with pre-eclampsia. 

PMID- 25750743
TI  - Health status and related factors in farmers by SF-12.
AB  - OBJECTIVES: This study was performed to understand farmers' health status by
      general characteristic, and to find out the related factors. METHODS: All the 984
      subjects were interviewed by means of a structured questionnaire and SF-12. Among
      them, only 812 were eligible for analysis. Statistical methods used included
      frequency, t-test, ANOVA, binary logistic regression with SPSS 19.0. RESULTS: In
      binary logistic regression, marital status, smoking, regular exercise and monthly
      day off were associated with physical component score. Marital status, smoking
      and score of pesticide protective device wearing were associated with mental
      component score. CONCLUSIONS: This study suggests that effort to develop health
      promotion programs for workers of agricultural industry considering these results
      can improve their perceived health status.

PMID- 25750744
TI  - Characterization of in vitro transcriptional responses of dorsal root ganglia
      cultured in the presence and absence of blastema cells from regenerating
      salamander limbs.
AB  - During salamander limb regeneration, nerves provide signals that induce the
      formation of a mass of proliferative cells called the blastema. To better
      understand these signals, we developed a blastema-dorsal root ganglia (DRG) co
      culture model system to test the hypothesis that nerves differentially express
      genes in response to cues provided by the blastema. DRG with proximal and distal
      nerve trunks were isolated from axolotls (Ambystoma mexicanum), cultured for five
      days, and subjected to microarray analysis. Relative to freshly isolated DRG,
      1,541 Affymetrix probe sets were identified as differentially expressed and many
      of the predicted genes are known to function in injury and neurodevelopmental
      responses observed for mammalian DRG. We then cultured 5-day DRG explants for an
      additional five days with or without co-cultured blastema cells. On Day 10, we
      identified 27 genes whose expression in cultured DRG was significantly affected
      by the presence or absence of blastema cells. Overall, our study established a
      DRG-blastema in vitro culture system and identified candidate genes for future
      investigations of axon regrowth, nerve-blastema signaling, and neural regulation
      of limb regeneration.

PMID- 25750745
TI  - Hydrogel: Preparation, characterization, and applications: A review.
AB  - Hydrogel products constitute a group of polymeric materials, the hydrophilic
      structure of which renders them capable of holding large amounts of water in
      their three-dimensional networks. Extensive employment of these products in a
      number of industrial and environmental areas of application is considered to be
      of prime importance. As expected, natural hydrogels were gradually replaced by
      synthetic types due to their higher water absorption capacity, long service life,
      and wide varieties of raw chemical resources. Literature on this subject was
      found to be expanding, especially in the scientific areas of research. However, a
      number of publications and technical reports dealing with hydrogel products from
      the engineering points of view were examined to overview technological aspects
      covering this growing multidisciplinary field of research. The primary objective
      of this article is to review the literature concerning classification of
      hydrogels on different bases, physical and chemical characteristics of these
      products, and technical feasibility of their utilization. It also involved
      technologies adopted for hydrogel production together with process design
      implications, block diagrams, and optimized conditions of the preparation
      process. An innovated category of recent generations of hydrogel materials was
      also presented in some details. 

PMID- 25750746
TI  - A review on solar cells from Si-single crystals to porous materials and quantum
      dots.
AB  - Solar energy conversion to electricity through photovoltaics or to useful fuel
      through photoelectrochemical cells was still a main task for research groups and
      developments sectors. In this article we are reviewing the development of the
      different generations of solar cells. The fabrication of solar cells has passed
      through a large number of improvement steps considering the technological and
      economic aspects. The first generation solar cells were based on Si wafers,
      mainly single crystals. Permanent researches on cost reduction and improved solar
      cell efficiency have led to the marketing of solar modules having 12-16% solar
      conversion efficiency. Application of polycrystalline Si and other forms of Si
      have reduced the cost but on the expense of the solar conversion efficiency. The
      second generation solar cells were based on thin film technology. Thin films of
      amorphous Si, CIS (copper-indium-selenide) and t-Si were employed. Solar
      conversion efficiencies of about 12% have been achieved with a remarkable cost
      reduction. The third generation solar cells are based on nano-crystals and nano
      porous materials. An advanced photovoltaic cell, originally developed for
      satellites with solar conversion efficiency of 37.3%, based on concentration of
      the solar spectrum up to 400 suns was developed. It is based on extremely thin
      concentration cells. New sensitizer or semiconductor systems are necessary to
      broaden the photo-response in solar spectrum. Hybrids of solar and conventional
      devices may provide an interim benefit in seeking economically valuable devices.
      New quantum dot solar cells based on CdSe-TiO2 architecture have been developed. 

PMID- 25750747
TI  - Endothelial progenitor cells regenerate infracted myocardium with
      neovascularisation development.
AB  - We achieved possibility of isolation, characterization human umbilical cord blood
      endothelial progenitor cells (EPCs), examination potency of EPCs to form new
      blood vessels and differentiation into cardiomyoctes in canines with acute
      myocardial infarction (AMI). EPCs were separated and cultured from umbilical cord
      blood. Their phenotypes were confirmed by uptake of double stains dioctadecyl
      tetramethylindocarbocyanine-labeled acetylated LDL and FITC-labeled Ulex
      europaeus agglutinin 1 (DILDL-UEA-1). EPCs of cord blood were counted. Human
      VEGFR-2 and eNOS from the cultured EPCs were assessed by qPCR. Human EPCs was
      transplanted intramyocardially in canines with AMI. ECG and cardiac enzymes (CK
      MB and Troponin I) were measured to assess severity of cellular damage.
      Histopathology was done to assess neovascularisation. Immunostaining was done to
      detect EPCs transdifferentiation into cardiomyocytes in peri-infarct cardiac
      tissue. qPCR for human genes (hVEGFR-2, and eNOS) was done to assess homing and
      angiogenic function of transplanted EPCs. Cultured human cord blood exhibited an
      increased number of EPCs and significant high expression of hVEGFR-2 and eNOS
      genes in the culture cells. Histopathology showed increased neovascularization
      and immunostaining showed presence of EPCs newly differentiated into
      cardiomyocyte-like cells. Our findings suggested that hEPCs can mediate
      angiogenesis and differentiate into cardiomyoctes in canines with AMI. 

PMID- 25750748
TI  - Diagnostic value of combined static-excretory MR Urography in children with
      hydronephrosis.
AB  - The aim of this study was to determine the feasibility, accuracy and diagnostic
      potential of combined static-excretory MR Urography in children with
      sonographically detected hydronephrosis. We prospectively evaluated 28 children
      (11 girls and 17 boys), mean age 8.3 years (range 2 months-16 years). Static
      excretory MR Urography was performed in all cases. The results of MR Urography
      were compared with the results of other imaging modalities, cystoscopy and
      surgery. In 28 children, 61 renal units were evaluated by MR Urography (the renal
      unit is the kidney and its draining ureter). The final diagnoses included: normal
      renal units (n = 23); uretropelvic junction obstruction (n = 14); megaureter (n =
      8); midureteric stricture (n = 1), complicated duplicated systems (n = 5), post
      ESWL non-obstructive dilation (n = 2), extrarenal pelvis (n = 4), dysplastic
      kidney (n = 4). Complex pathology and more than one disease entity in were found
      in 7 children. The MRI diagnosis correlated with the final diagnosis in 57 units,
      with diagnostic accuracy 93.4%. In conclusions static and excretory MRU give both
      morphological and functional information in a single examination without exposure
      to ionizing radiation and iodinated contrast agent. It is a valuable imaging
      technique for children with upper urinary tract dilatation; especially in cases
      of complex congenital pathologies and severely hydronephrotic kidney. 

PMID- 25750749
TI  - A statistical experimental design approach to evaluate the influence of various
      penetration enhancers on transdermal drug delivery of buprenorphine.
AB  - A series of drug-in-adhesive transdermal drug delivery systems (patch) with
      different chemical penetration enhancers were designed to deliver drug through
      the skin as a site of application. The objective of our effort was to study the
      influence of various chemical penetration enhancers on skin permeation rate and
      adhesion properties of a transdermal drug delivery system using Box-Behnken
      experimental design. The response surface methodology based on a three-level,
      three-variable Box-Behnken design was used to evaluate the interactive effects on
      dependent variables including, the rate of skin permeation and adhesion
      properties, namely peel strength and tack value. Levulinic acid, lauryl alcohol,
      and Tween 80 were used as penetration enhancers (patch formulations, containing 0
      8% of each chemical penetration enhancer). Buprenorphine was used as a model
      penetrant drug. The results showed that incorporation of 20% chemical penetration
      enhancer into the mixture led to maximum skin permeation flux of buprenorphine
      from abdominal rat skin while the adhesion properties decreased. Also that skin
      flux in presence of levulinic acid (1.594 MUg/cm(2) h) was higher than Tween 80
      (1.473 MUg/cm(2) h) and lauryl alcohol (0.843 MUg/cm(2) h), and in mixing these
      enhancers together, an additional effect was observed. Moreover, it was found
      that each enhancer increased the tack value, while levulinic acid and lauryl
      alcohol improved the peel strength but Tween 80 reduced it. These findings
      indicated that the best chemical skin penetration enhancer for buprenorphine
      patch was levulinic acid. Among the designed formulations, the one which
      contained 12% (wt/wt) enhancers exhibited the highest efficiency. 

PMID- 25750750
TI  - An enhanced method for human action recognition.
AB  - This paper presents a fast and simple method for human action recognition. The
      proposed technique relies on detecting interest points using SIFT (scale
      invariant feature transform) from each frame of the video. A fine-tuning step is
      used here to limit the number of interesting points according to the amount of
      details. Then the popular approach Bag of Video Words is applied with a new
      normalization technique. This normalization technique remarkably improves the
      results. Finally a multi class linear Support Vector Machine (SVM) is utilized
      for classification. Experiments were conducted on the KTH and Weizmann datasets.
      The results demonstrate that our approach outperforms most existing methods,
      achieving accuracy of 97.89% for KTH and 96.66% for Weizmann. 

PMID- 25750751
TI  - Solar drying of whole mint plant under natural and forced convection.
AB  - Two identical prototype solar dryers (direct and indirect) having the same
      dimensions were used to dry whole mint. Both prototypes were operated under
      natural and forced convection modes. In the case of the later one the ambient air
      was entered the dryer with the velocity of 4.2 m s(-1). The effect of flow mode
      and the type of solar dryers on the drying kinetics of whole mint were
      investigated. Ten empirical models were used to fit the drying curves; nine of
      them represented well the solar drying behavior of mint. The results indicated
      that drying of mint under different operating conditions occurred in the falling
      rate period, where no constant rate period of drying was observed. Also, the
      obtained data revealed that the drying rate of mint under forced convection was
      higher than that of mint under natural convection, especially during first hours
      of drying (first day). The values of the effective diffusivity coefficient for
      the mint drying ranged between 1.2 * 10(-11) and 1.33 * 10(-11) m(2) s(-1). 

PMID- 25750753
TI  - Experimental and modeling study on effects of N2 and CO2 on ignition
      characteristics of methane/air mixture.
AB  - The ignition delay times of methane/air mixture diluted by N2 and CO2 were
      experimentally measured in a chemical shock tube. The experiments were performed
      over the temperature range of 1300-2100 K, pressure range of 0.1-1.0 MPa,
      equivalence ratio range of 0.5-2.0 and for the dilution coefficients of 0%, 20%
      and 50%. The results suggest that a linear relationship exists between the
      reciprocal of temperature and the logarithm of the ignition delay times.
      Meanwhile, with ignition temperature and pressure increasing, the measured
      ignition delay times of methane/air mixture are decreasing. Furthermore, an
      increase in the dilution coefficient of N2 or CO2 results in increasing ignition
      delays and the inhibition effect of CO2 on methane/air mixture ignition is
      stronger than that of N2. Simulated ignition delays of methane/air mixture using
      three kinetic models were compared to the experimental data. Results show that
      GRI_3.0 mechanism gives the best prediction on ignition delays of methane/air
      mixture and it was selected to identify the effects of N2 and CO2 on ignition
      delays and the key elementary reactions in the ignition chemistry of methane/air
      mixture. Comparisons of the calculated ignition delays with the experimental data
      of methane/air mixture diluted by N2 and CO2 show excellent agreement, and
      sensitivity coefficients of chain branching reactions which promote mixture
      ignition decrease with increasing dilution coefficient of N2 or CO2. 

PMID- 25750752
TI  - Roles of dehydrin genes in wheat tolerance to drought stress.
AB  - Physiological parameters and expression levels of drought related genes were
      analyzed in early vegetative stage of two bread wheat cultivars (Sids and Gmiza)
      differ in drought tolerance capacity. Both cultivars were imposed to gradual
      water depletion started on day 17 till day 32 after sowing. Sids, the more
      tolerant cultivar to drought showed higher fresh and dry weights than the drought
      sensitive genotype, Gmiza. Under water stress, Sids had higher membrane stability
      index (MSI), lower accumulated H2O2 and higher activity of the antioxidant
      enzymes; catalase (CAT), guaiacol peroxidase (GPX), ascorbate peroxidase (APX)
      and superoxide dismutase (SOD) than Gmiza. On the other hand, the differential
      expression patterns of the genes dhn, wcor and dreb were observed due to water
      deficit intensity according to cultivar's tolerance to drought. The DNA sequence
      alignment of dun showed high similarity of about 80-92% identities with other
      related plants. The most striking overall observed trend was the highly induction
      in the expression of dun, wcor and dreb in leaves of the tolerant genotype, Sids
      under severe water stress. 

PMID- 25750754
TI  - Theoretical and experimental studies on the corrosion inhibition potentials of
      some purines for aluminum in 0.1 M HCl.
AB  - Experimental aspect of the corrosion inhibition potential of adenine (AD),
      guanine (GU) and, hypoxanthine (HYP) was carried out using weight loss,
      potentiodynamic polarization and electrochemical impedance spectroscopy (EIS)
      methods while the theoretical aspect of the work was carried out by calculations
      of semi-empirical parameters (for AM1, MNDO, CNDO, PM3 and RM1 Hamiltonians),
      Fukui functions and inhibitor-metal interaction energies. Results obtained from
      the experimental studies were in good agreement and indicated that adenine (AD),
      guanine (GU) and hypoxanthine (HYP) are good adsorption inhibitors for the
      corrosion of aluminum in solutions of HCl. Data obtained from electrochemical
      experiment revealed that the studied purines functioned by adsorption on the
      aluminum/HCl interface and inhibited the cathodic half reaction to a greater
      extent and anodic half reaction to a lesser extent. The adsorption of the purines
      on the metal surface was found to be exothermic and spontaneous. Deviation of the
      adsorption characteristics of the studied purines from the Langmuir adsorption
      model was compensated by the fitness of Flory Huggins and El Awardy et al.
      adsorption models. Quantum chemical studies revealed that the experimental
      inhibition efficiencies of the studied purines are functions of some quantum
      chemical parameters including total energy of the molecules (TE), energy gap (E L
      H), electronic energy of the molecule (EE), dipole moment and core-core repulsion
      energy (CCR). Fukui functions analysis through DFT and MP2 theories indicated
      slight complications and unphysical results. However, results obtained from
      calculated Huckel charges, molecular orbital and interaction energies, the
      adsorption of the inhibitors proceeded through the imine nitrogen (N5) in GU,
      emanine nitrogen (N7) in AD and the pyridine nitrogen (N5) in HPY. 

PMID- 25750755
TI  - Modifications induced by gamma irradiation to Makrofol polymer nuclear track
      detector.
AB  - The aim of the present study was extended from obtaining information about the
      interaction of gamma rays with Makrofol DE 7-2 track detector to introduce the
      basis that can be used in concerning simple sensor for gamma irradiation and bio
      engineering applications. Makrofol polymer samples were irradiated with 1.25 MeV
      (60)Co gamma radiations at doses ranging from 20 to 1000 kG y. The modifications
      of irradiated samples so induced were analyzed using UV-vis spectrometry,
      photoluminescence spectroscopy, and the measurements of Vickers' hardness.
      Moreover, the change in wettability of irradiated Makrofol was investigated by
      the contact angle determination of the distilled water. UV-vis spectroscopy shows
      a noticeable decrease in the energy band gap due to gamma irradiation. This
      decrease could be attributed to the appearance of a shift to UV spectra toward
      higher wavelength region after irradiation. Photoluminescence spectra reveal a
      remarkable change in the integrated photoluminescence intensity with increasing
      gamma doses, which may be resulted from some matrix disorder through the creation
      of some defected states in the irradiated polymer. The hardness was found to
      increase from 4.78 MPa for the unirradiated sample to 23.67 MPa for the highest
      gamma dose. The contact angle investigations show that the wettability of the
      modified samples increases with increasing the gamma doses. The result obtained
      from present investigation furnishes evidence that the gamma irradiations are a
      successful technique to modify the Makrofol DE 7-2 polymer properties to use it
      in suitable applications. 

PMID- 25750756
TI  - Hybrid composites prepared from Industrial waste: Mechanical and swelling
      behavior.
AB  - In this assessment, hybrid composites were prepared from the combination of
      industrial waste, as marble waste powder (MWP) with conventional fillers, carbon
      black (CB) as well as silica as reinforcing material, incorporated with natural
      rubber (NR). The properties studied were curing, mechanical and swelling
      behavior. Assimilation of CB as well as silica into MWP containing NR compound
      responded in decreasing the scorch time and cure time besides increasing in the
      torque. Additionally, increasing the CB and silica in their respective NR hybrid
      composite increases the tensile, tear, modulus, hardness, and cross-link density,
      but decreases the elongation and swelling coefficient. The degradation property
      e.g., thermal aging of the hybrid composite was also estimated. The overall
      behavior at 70  degrees C aging temperature signified that the replacement of MS
      by CB and silica improved the aging performance. 

PMID- 25750757
TI  - Genetic diversity of geographically distinct Streptococcus dysgalactiae isolates
      from fish.
AB  - Streptococcus dysgalactiae is an emerging pathogen of fish. Clinically, infection
      is characterized by the development of necrotic lesions at the caudal peduncle of
      infected fishes. The pathogen has been recently isolated from different fish
      species in many countries. Twenty S. dysgalactiae isolates collected from Japan,
      Taiwan, Malaysia and Indonesia were molecularly characterized by biased
      sinusoidal field gel electrophoresis (BSFGE) using SmaI enzyme, and tuf gene
      sequencing analysis. DNA sequencing of ten S. dysgalactiae revealed no genetic
      variation in the tuf amplicons, except for three strains. The restriction
      patterns of chromosomal DNA measured by BSFGE were differentiated into six
      distinct types and one subtype among collected strains. To our knowledge, this
      report gives the first snapshot of S. dysgalactiae isolates collected from
      different countries that are localized geographically and differed on a
      multinational level. This genetic unrelatedness among different isolates might
      suggest a high recombination rate and low genetic stability. 

PMID- 25750758
TI  - The Response to Challenge Scale (RCS): The Development and Construct Validity of
      an Observer-Rated Measure of Children's Self-Regulation.
AB  - In this manuscript, I present an observer-rated measure of child self-regulation,
      the Response to Challenge Scale (RCS). The RCS was designed to measure children's
      cognitive, affective, and motor regulation in response to a physical challenge
      course. 198 children (Kindergarten through fifth grade) were evaluated using the
      RCS. All children individually completed a challenge course on two separate
      occasions four months apart. During their completion of the tasks, research
      trained observers rated the degree to which children exhibited cognitive,
      affective, and motor regulation. In a fully-crossed research design, five raters
      on Occasion 1 and six raters on Occasion 2 rated all children. I examined the RCS
      within the Generalizability Theory (GT) framework to analyze construct validity
      (PRS). Results demonstrated that raters are able to distinguish between
      children's self-regulation in various domains, providing some validity evidence
      for the RCS, and supporting the theory that self-regulation is a construct that
      is evidenced in different domains (Baumeister, 1997).

PMID- 25750759
TI  - Implications of miRNAs in Colorectal Cancer Chemoresistance.
AB  - With the exponential growth of research efforts on non-coding microRNAs (miRNAs)
      in the past decade, miRNAs have been demonstrated to be important in many major
      human diseases, including diabetes, heart disease, and cancer. Due to the broad
      regulatory function of miRNAs, alterations of their expression can have profound
      consequences on multiple critical genes and pathways. One of the major issues
      related to the success of treating advanced colorectal cancer is chemoresistance.
      In this review, we will present some of the recent advancements in miRNA research
      related to chemoresistance mechanisms to 5-FU based chemotherapy in colorectal
      cancer and cancer stem cells. We believe that this miRNA-mediated resistance
      mechanism will offer novel strategies to develop future anti-cancer therapies.

PMID- 25750760
TI  - HIV-Care Outcome in Saudi Arabia; a Longitudinal Cohort.
AB  - BACKGROUND: Clinical characteristics of HIV-1 infection in people inhabiting
      Western, Sub-Saharan African, and South-East Asian countries are well recognized.
      However, very little information is available with regard to HIV-1 infection and
      treatment outcome in MENA countries including the Gulf Cooperation Council (GCC)
      states. METHODS: Clinical, demographic and epidemiologic characteristics of 602
      HIV-1 infected patients followed in the adult Infectious Diseases Clinic of King
      Faisal Specialist Hospital and Research Centre, in Riyadh, Kingdom of Saudi
      Arabia a tertiary referral center were longitudinally collected from 1989 to
      2010. RESULTS: Of the 602 HIV-1 infected patients in this observation period, 70%
      were male. The major mode of HIV-1 transmission was heterosexual contact (55%).
      At diagnosis, opportunistic infections were found in 49% of patients, most
      commonly being pneumocysitis. AIDS associated neoplasia was also noted in 6% of
      patients. A hundred and forty-seven patients (24%) died from the cohort by the
      end of the observation period. The mortality rate peaked in 1992 at 90 deaths per
      1000 person-year, whereas the mortality rate gradually decreased to <1% from 1993
      2010. In 2010, 71% of the patients were receiving highly active retroviral
      therapy. CONCLUSIONS: These data describe the clinical characteristic of HIV-1
      infected patients at a major tertiary referral hospital in KSA over a 20-year
      period. Initiation of antiretroviral therapy resulted in a significant reduction
      in both morbidity and mortality. Future studies are needed in the design and
      implementation of targeted treatment and prevention strategies for HIV-1
      infection in KSA.

PMID- 25750761
TI  - Plasma Amylin and Cognition in Diabetes in the Absence and the Presence of
      Insulin Treatment.
AB  - BACKGROUND: Plasma amylin is positively associated with cognitive function in
      humans. Amylin treatment improves memory in Alzheimer's mouse models. However,
      the relationship between plasma amylin, diabetes and cognition is not clear.
      OBJECTIVES: In this study we examined the concentration of plasma amylin, its
      relationship with diabetes and cognition. MATERIAL AND METHOD: A cross-sectional,
      homebound elderly population with data of plasma amylin under fasting condition
      and cognitive measurements was used. RESULTS: We found that subjects with a long
      and chronic duration of diabetes were more likely to take insulin treatment and
      have reduced secretion of amylin. Compared to non-diabetics, diabetic subjects
      without insulin treatment had a higher concentration, but those with insulin
      treatment had a lower concentration, of plasma amylin [median (Q1, Q3): 20 (11.0,
      36.2) vs. 25.2 (13.2, 50.6) vs. 15.0 (4.9, 33.8), p<0.0001]. In the whole sample
      vs. in the absence of diabetes, plasma amylin was positively associated with
      logical memory delayed recall (beta= +0.61, SE=0.25, p=0.02 vs. beta=+0.80,
      SE=0.33, p=0.02) and block design (beta=+0.62, SE=0.24, p=0.009 vs. beta=+0.93,
      SE=0.31, p=0.003), and negatively associated with Trailmaking A scores (beta= 
      6.21, SE=1.55, p<0.0001 vs. beta=-7.51, SE=1.95, p=0.0001) and Trailmaking B
      (beta= -4.32, SE=2.13, p=0.04 vs. beta= -5.86, SE=2.73, p=0.04). All these
      relationships disappeared in the presence of diabetes regardless the treatment.
      CONCLUSION: This study suggests that secretion of amylin by pancreas compensates
      and then deteriorates depending on the duration of diabetes. Amylin's activities
      for cognition are impaired in the presence of diabetes.

PMID- 25750762
TI  - Optimal Concentration of 2,2,2-Trichloroacetic Acid for Protein Precipitation
      Based on Response Surface Methodology.
AB  - For low protein concentrations containing biological samples (in proteomics) and
      for non proteinaceous compound assays (in bioanalysis), there is a critical need
      for a simple, fast, and cost-effective protein enrichment or precipitation
      method. However, 2,2,2-trichloroacetic acid (TCA) is traditionally used for
      protein precipitation at ineffective concentrations for very low protein
      containing samples. It is hypothesized that response surface methodology, can be
      used to systematically identify the optimal TCA concentration for protein
      precipitation in a wider concentration range. To test this hypothesis, a central
      composite design is used to assess the effects of two factors (X1 = volume of
      aqueous solution of protein, and X2 = volume of TCA solution 6.1N) on the optical
      absorbance of the supernatant (Y1), and the percentage of protein precipitated
      (Y2). Using either bovine serum albumin (BSA) as a model protein or human urine
      (with 20 ppm protein content), 4% w/v (a saddle point) is the optimal
      concentration of the TCA solution for protein precipitation that is visualized by
      SDS-PAGE analysis. At this optimal concentration, the Y2-values range from 76.26
      to 92.67% w/w for 0.016 to 2 mg/mL of BSA solution. It is also useful for protein
      enrichment and xenobiotic analysis in protein-free supernatant as applied to
      tenofovir (a model HIV microbicide). In these conditions, the limit of detection
      and limit of quantitation of tenofovir are respectively 0.0014 mg/mL and 0.0042
      mg/mL. This optimal concentration of TCA provides optimal condition for protein
      purification and analysis of any xenobiotic compound like tenofovir.

PMID- 25750763
TI  - Tumor Infiltrating Lymphocytes - The Next Step in Assessing Outcome and Response
      to Treatment in Patients with Breast Cancer.
AB  - Tumor infiltrating lymphocytes are studied for their potential as new clinically
      useful prognostic and predictive biomarkers in patients with triple negative and
      HER-2/neu amplified breast cancer. This area of research could also help guide
      the development of novel therapeutic approaches for these diseases.

PMID- 25750764
TI  - The Vps39-like TRAP1 is an effector of Rab5 and likely the missing Vps3 subunit
      of human CORVET.
AB  - Membrane fusion in the endocytic pathway is mediated by a protein machinery
      consistent of Rab GTPases, tethering factors and SNAREs. In yeast, the endosomal
      CORVET and lysosomal HOPS tethering complexes share 4 of their 6 subunits. The 2
      additional subunits in each complex - Vps3 and Vps8 for CORVET, and the
      homologous Vps39 and Vps41 for HOPS - bind directly to Rab5 and Rab7,
      respectively. In humans, all subunits for HOPS have been described. However,
      human CORVET remains poorly characterized and a homolog of Vps3 is still missing.
      Here we characterize 2 previously identified Vps39 isoforms, hVps39-1/hVam6/TLP
      and hVps39-2/TRAP1, in yeast and HEK293 cells. None of them can compensate the
      loss of the endogenous yeast Vps39, though the specific interaction of hVps39-1
      with the virus-specific LT protein was reproduced. Both human Vps39 proteins show
      a cytosolic localization in yeast and mammalian cells. However, hVps39-2/TRAP1
      strongly co-localizes with co-expressed Rab5 and interacts directly with Rab5-GTP
      in vitro. We conclude that hVps39-2/TRAP1 is an endosomal protein and an effector
      of Rab5, suggesting a role of the protein as a subunit of the putative human
      CORVET complex.

PMID- 25750766
TI  - Coping, acculturation, and psychological adaptation among migrants: a theoretical
      and empirical review and synthesis of the literature.
AB  - Given the continuous, dynamic demographic changes internationally due to
      intensive worldwide migration and globalization, the need to more fully
      understand how migrants adapt and cope with acculturation experiences in their
      new host cultural environment is imperative and timely. However, a comprehensive
      review of what we currently know about the relationship between coping behavior
      and acculturation experience for individuals undergoing cultural changes has not
      yet been undertaken. Hence, the current article aims to compile, review, and
      examine cumulative cross-cultural psychological research that sheds light on the
      relationships among coping, acculturation, and psychological and mental health
      outcomes for migrants. To this end, this present article reviews prevailing
      literature pertaining to: (a) the stress and coping conceptual perspective of
      acculturation; (b) four theoretical models of coping, acculturation and cultural
      adaptation; (c) differential coping pattern among diverse acculturating migrant
      groups; and (d) the relationship between coping variabilities and acculturation
      levels among migrants. In terms of theoretical understanding, this review points
      to the relative strengths and limitations associated with each of the four
      theoretical models on coping-acculturation-adaptation. These theories and the
      empirical studies reviewed in this article further highlight the central role of
      coping behaviors/strategies in the acculturation process and outcome for migrants
      and ethnic populations, both conceptually and functionally. Moreover, the review
      shows that across studies culturally preferred coping patterns exist among
      acculturating migrants and migrant groups and vary with migrants' acculturation
      levels. Implications and limitations of the existing literature for coping,
      acculturation, and psychological adaptation research are discussed and
      recommendations for future research are put forth.

PMID- 25750765
TI  - Dietary Risk Reduction Factors for the Barrett's Esophagus-Esophageal
      Adenocarcinoma Continuum: A Review of the Recent Literature.
AB  - Esophageal adenocarcinoma (EA) incidence is among the most rapidly increasing of
      any cancer type in the U.S., and prognosis is poor. Prevalence of the potential
      precursor lesion, Barrett's esophagus (BE), is also increasing. Candidates for
      safe and effective risk reduction strategies are needed, potentially including
      dietary components. In this qualitative review, we summarize recently published
      epidemiologic studies, in context of earlier work, on dietary intake and BE-EA
      outcomes. Potential cohort study/intervention trial candidates which could be
      increased to reduce BE-EA development include intake of: (1) fruits and
      vegetables; vegetables; fruit (EA only); (2) beta-carotene and vitamins C and E;
      (3) folate (EA only); and (4) total fiber (EA only). Also, (5) red and processed
      meat intake could be targeted for dietary reduction/omission to reduce EA
      development. Few dietary constituents have been evaluated among EA patients to
      examine associations with mortality, thus interventions conducted among EA
      patients are premature.

PMID- 25750767
TI  - Perceived behavioral control, intention to get vaccinated, and usage of online
      information about the human papillomavirus vaccine.
AB  - Objective: Human papillomavirus (HPV) and the HPV vaccine have been examined
      through multiple lenses over the past several years, though there is little work
      examining the role of perceived behavioral control (PBC) and its impact on
      potential recipients retrieving, understanding, and using online information with
      regard to the vaccine. Method: This study used survey data to examine the role of
      PBC as a moderator between attitudes and intention, and subjective norms (SN) and
      intention to get the HPV vaccine; and PBC as a moderator when seeking out
      Facebook, YouTube, and Twitter as information sources about HPV. Support was
      found for each prediction. Results: The interaction term of SN * PBC in
      particular had a strong influence on intention to get the vaccine. Discussion:
      Planned behavior variables explain intention to get the HPV vaccine, but data
      also suggest a need to root this research within intervention-based strategies.

PMID- 25750768
TI  - Beliefs about causes of weight gain, effective weight gain prevention strategies,
      and barriers to weight management in the Australian population.
AB  - Purpose: To identify beliefs held by the general public regarding causes of
      weight gain, weight prevention strategies, and barriers to weight management; and
      to examine whether such beliefs predict the actual body mass of participants.
      Methods: A questionnaire-based survey was administered to participants recruited
      from regional and metropolitan areas of Australia. This questionnaire obtained
      demographic information, height, weight; as well as beliefs about causes of
      weight gain, weight prevention strategies, and barriers to weight management.
      Results: The sample consisted of 376 participants (94 males, 282 females) between
      the ages of 18 years and 88 years (mean age = 43.25, SD = 13.64). The range and
      nature of the belief dimensions identified suggest that the Australian public
      have an understanding of the interaction between internal and external factors
      that impact on weight gain but also prevent successful weight management. Beliefs
      about prevention strategies and barriers to effective weight management were
      found to predict the participants' actual body mass, even after controlling for
      demographic characteristics. Conclusions: The general public have a good
      understanding of the multiple contributing factors to weight gain and successful
      weight management. However, this understanding may not necessarily lead to
      individuals adopting the required lifestyle changes that result in achievement or
      maintenance of healthy weight levels.

PMID- 25750769
TI  - Sexually transmitted infections among migrants' wives remaining in rural homes -
      a pilot study of the remaining women in rural Wuhan, China.
AB  - The growing HIV/AIDS epidemic in China appears to be related to the vast rural-to
      urban migration, with rural migrants serving as a "living bridge" for the spread
      of HIV. The purpose of this study is to examine whether migrants' wives remaining
      in rural homes play a role in spreading the virus. Participants were recruited
      from 12 rural villages. Social and demographic factors, sexual behaviour, and
      HIV/AIDS knowledge were assessed using survey questionnaire. Reproductive tract
      infection (RTI; syphilis, chlamydia, gonorrhea, vaginalis trichomonas, and
      candidiasis) were assessed using blood and vaginal specimens. Among the total 63
      participants, 28 (44.4%) were wives remaining behind while their husbands
      migrated to a city ("remaining") and 35 were women whose spouses remained in the
      rural setting ("comparison"). The reported median duration (inter-quarter range
      (IQR)) since the last episode of sex with husband was nine months (IQR: 7-15) for
      the remaining women and three months (IQR: 2-7) for the comparison women (Z =
      3.95, p < 0.01). RTI was 32.1% for remaining women and 17.1% for the comparison
      women (Odds ratio = 2.28, 95%CI: 0.70-7.48, p = 0.165). The high rate of RTI
      suggests that remaining women in rural areas may be at increased risk for
      acquiring HIV infection compared to women whose husbands remained in rural homes.

PMID- 25750770
TI  - Health behaviors among college students: the influence of future time perspective
      and basic psychological need satisfaction.
AB  - Health behavior change may prevent many fatal diseases, and may be influenced by
      social and motivational constructs. We assessed the interaction effect of future
      time perspective and basic psychological need fulfillment on positive and
      negative health behaviors. Future time perspective was associated with more
      positive, and less negative, health behaviors. Need fulfillment was associated
      with only positive health behaviors. In moderation analyses, individuals
      reporting both high need fulfillment and future perspective reported greater
      positive health behaviors, and were especially unlikely to smoke. Enhancing
      future-mindedness and supporting need satisfaction in interventions targeting
      modifiable health behaviors is encouraged.

PMID- 25750771
TI  - Stress and law enforcers: testing the relationship between law enforcement work
      stressors and health-related issues.
AB  - This study examines the relationship between law enforcement work-related
      stressors and health issues. Specifically, this study attempts to determine the
      effects of stress-producing factors (e.g. vigorous activities at work, shift
      change, perceived danger associated with police work, etc.) on physiological
      health-related issues (e.g. the number of reported health issues, high blood
      pressure, back pain, and headaches) and psychosocial behavior problems (e.g.
      alcohol consumption and cigarette smoking) among police officers. The analyses
      are based on a total 1632 law enforcement officers, who represent 51 police
      agencies in the three major cities, New York City, Dallas Texas, and Minneapolis,
      USA. The research findings that emerged from this study show that the number of
      days in vigorous activities and perceived physiological demands have the
      strongest influence on the number of health-related issues. Working without a
      partner and frequent shift changes had the strongest influence on alcohol
      consumption by police officers.

PMID- 25750772
TI  - Utilization of formal health services for children aged 1-5 in Aceh after the
      2004 tsunami: Which children did not receive the health care they needed?
      Implications for other natural disaster relief efforts.
AB  - Aceh, Indonesia, was the hardest-hit area in the December 26, 2004 Indian Ocean
      earthquake and tsunami, with more than 500,000 people displaced, 120,000 people
      dead, and total damages and losses estimated at $4.5 billion. The relief effort
      following the tsunami was also immense, with billions of dollars of aid pledged
      to this province alone. Since then, there have been several natural disasters,
      including Typhoon Haiyan, which have caused great loss of life and displacement
      and for which these results are applicable. This study aimed to determine and
      assess utilization patterns of health services for children under the age of five
      with diarrhea, cough and difficulty breathing, fever, or skin disease and to
      identify determinants of formal and non-formal healthcare usage. A household
      survey of 1439 households was administered to caretakers of children aged 1-5
      years. A sample of clusters within Banda Aceh and Aceh Besar were selected and
      those caretakers within the cluster who fit the inclusion criteria were
      interviewed. In the two weeks prior to the survey, 78.3% of respondents utilized
      formal health services as the first line of care for their child's illness
      episode. Factors significantly associated with decreased formal healthcare usage
      for the sick children were if the children were living in a displaced household,
      if the children's mother or father were not living, and if the children's
      caretaker was not the mother. Although utilization of formal health services for
      children was quite high after the tsunami, there were certain children who
      received significantly less care, including those who were displaced, those who
      were being cared for by someone other than their mother, and those for whom one
      or both parents had died. Among the recommendations are suggestions to target
      these children to ensure that they receive the health care they need.

PMID- 25750773
TI  - Languages of Grief: a model for understanding the expressions of the bereaved.
AB  - The aim of this work is to provide an overview of the key features of the
      expressions of grief. Grief is a response to loss or anticipated loss. Although
      universal, its oral and nonverbal expression varies across cultures and
      individuals. Loss is produced by an event perceived to be negative to varying
      degrees by the individuals involved and has the potential to trigger long-term
      changes in a person's cognitions and relationships. The languages used by the
      bereaved to express grief differ from the language used by professionals,
      creating dissonance between the two. Data were obtained from English language
      Medline and CINAHL databases, from professional and personal experiences,
      interviews with experts, and exploration of cemetery memorials. Blog websites and
      social networks provided additional materials for further refinement of the
      model. Content analysis of the materials and agreement by the authors as to the
      themes resulted in the development of the model. To bridge the gap between
      professional language and that used by the bereaved, a Languages of Grief model
      was developed consisting of four Modes of Expression, four Types of Language,
      plus three Contingent Factors. The Languages of Grief provides a framework for
      comprehending the grief of the individual, contributing to clinical
      understanding, and fruitful exploration by professionals in better understanding
      the use of languages by the bereaved. Attention to the Modes of Expression, Types
      of Language, and Contingent Factors provides the professional with a richer
      understanding of the grieving individual, a step in providing appropriate support
      to the bereaved. The Languages of Grief provides a framework for application to
      discrete occurrences with the goal of understanding grief from the perspective of
      the bereaved.

PMID- 25750774
TI  - Is pubertal timing associated with involvement in bullying in middle adolescence?
AB  - Off-time pubertal maturation is associated with mental disorders, presumably due
      to stress caused by deviation from peers that could also attract negative
      attention and result in being bullied. Stress related to off-time maturation
      could be acted out by involving oneself in bullying behavior. The associations
      between pubertal timing and involvement in bullying have so far not been a focus
      of research. The objective is to explore associations between off-time pubertal
      maturation and involvement in bullying. Cross-sectional and longitudinal
      associations between self-reported pubertal timing and involvement in bullying as
      victims and perpetrators were studied in a sample of 2070 Finnish adolescents
      aged 15-17 who participated in the Adolescent Mental Health Cohort Study.
      Internalizing (depression) and externalizing (conduct disorder) symptoms were
      controlled for. The adolescents were recruited to response the baseline survey in
      2002-2003 (T1) and follow-up two years later (T2). In T1, response rate was 94.4%
      of all eligible students. The 2070 participants in T2 comprised 63.1% of the T1
      participants. Early maturation among boys was cross-sectionally associated with
      being a bully, and late maturation with exclusion from peer group. After two
      years, the associations had disappeared. Among girls, no associations were
      detected between pubertal timing and involvement in bullying. Off-time pubertal
      maturation places boys at risk for involvement in bullying. The influence is
      transient and supports the stressful change hypothesis of pubertal timing.

PMID- 25750775
TI  - Physical restraint use and older patients' length of hospital stay.
AB  - In both acute care and residential care settings, physical restraints are
      frequently used in the management of patients, older people in particular.
      Recently, the negative outcomes of physical restraint use have often been
      reported, but very limited research effort has been made to examine whether such
      nursing practice have any adverse effects on patients' length of stay (LOS) in
      hospitals. The aim of this study was to examine the association between physical
      restraint use on older patients during hospitalization and their LOS. Medical
      records of 910 older patients aged 60 years and above admitted to one of the Hong
      Kong public hospitals in 2007 were randomly selected and recorded during July to
      September 2011. The recorded items included patients' general health status,
      physical and cognitive function, the use of physical restraints, and patients'
      LOS. Hierarchical regression analysis was conducted to analyze the data. The
      results indicated that older patients' general health status, physical, and
      cognitive function were important factors affecting their LOS. Independent of
      these factors, the physical restraint use was still significantly predictive of
      longer LOS, and these two blocks of variables together served as an effective
      model in predicting older patients' LOS in the hospital. Since physical restraint
      use has been found to be predictive of longer hospital stay, physical restraints
      should be used with more caution and the use of it should be reduced on older
      patients in the hospital caring setting. All relevant health care staff should be
      aware of the negative effects of physical restraint use and should reduce the use
      of it in hospital caring and nursing home settings.

PMID- 25750776
TI  - Substance abuse prevention in Cape Town's peri-urban settlements: local health
      trainers' perspectives.
AB  - South Africa currently experiences high levels of alcohol and other drug (AOD)
      abuse. As a result there is a need for the initiation of regional AOD abuse
      prevention programmes with a specific focus on youth prevention strategies. The
      Medical Knowledge Institute (MKI) is a non-profit organisation which develops and
      facilitates health information workshops to members of disadvantaged peri-urban
      communities in South Africa. This research investigated the views of eight local
      MKI health trainers on factors contributing to AOD abuse in their communities.
      Although the expected focus of the discussion was on prevention strategies and
      effective interventions, the trainers placed more emphasis on the individual and
      community factors influencing AOD abuse. The themes which emerged through the
      research included: status, government, (di)stress, gender, recreation,
      consequences and community. This research holds significance as it has the
      potential to assist further development of community-based AOD prevention
      workshops and to guide public health policy and service development for AOD
      abuse.

PMID- 25750777
TI  - Assessing base rates of sexual behavior using the unmatched count technique.
AB  - Estimating the prevalence of sexual behaviors is difficult because of self-report
      biases. This is particularly relevant in assessing high-risk sexual behaviors for
      the purpose of reducing the transmission and acquisition of sexually transmitted
      infections (STIs) and HIV/AIDS. The present study employed the unmatched count
      technique (UCT), which provides estimates of the prevalence of risky sexual
      behaviors without requiring participants to confess to socially undesirable or
      stigmatized behaviors. Compared to a standard, anonymous self-report
      questionnaire, the UCT protocol revealed that people were less likely to notify
      their partners about STIs or discuss their history of sexual experiences. Effects
      were particularly large in women suggesting that women may be more likely to
      misrepresent their sexual behaviors. The findings suggest that conventional,
      anonymous self-report questionnaire data of base rates of risky sexual behavior
      and sexual communication are consistently inaccurate. These discrepant base rates
      suggest that the UCT might provide a better estimate of the frequency of these
      behaviors. Results suggest that inconsistent sexual behavior is more rampant than
      anonymous questionnaires suggest. They also underscore the need for improvements
      in the anonymity of assessment of sexual behaviors, which could in turn improve
      the targeting of prevention efforts. Results have important public health
      implications because accurate assessment of sexual behaviors is crucial for
      developing effective STI prevention interventions among target populations.

PMID- 25750778
TI  - Hopelessness, individualism, collectivism, and substance use among young rural-to
      urban migrants in China.
AB  - The current study aimed to investigate the impact of individualism, collectivism,
      and hopelessness on substance use. Hopelessness was hypothesized as a mediator
      between individualism and substance use, and between collectivism and substance
      use. We tested the hypothesis using a survey of 641 young rural-to-urban migrants
      in China. Consistent with our hypotheses, individualistic orientation predicted
      increased hopelessness and subsequently predicted more substance use, whereas
      collectivistic orientation was associated with decreased hopelessness and
      subsequently predicted less substance use. Hopelessness fully mediated the
      relations between individualism and substance use and between collectivism and
      substance use. The theoretical and practical implications of these findings were
      discussed.

PMID- 25750779
TI  - Cortisol reactivity to psychosocial stress is greater in sexual risk takers.
AB  - Several studies have reported an association between deviant behaviour and
      cortisol reactivity to stress. However, relatively few studies have investigated
      the relationship between psychobiological stress reactivity and sexual risk
      taking behaviours. In this study, cortisol reactivity to the Trier Social Stress
      Test (TSST) was measured in 26 healthy young adults prior to the administration
      of a sexual health and behaviour questionnaire. The cortisol response to the TSST
      was greater in those individuals who reported that at least one of their previous
      two sexual partners was someone whom they had just met. Results are discussed in
      the context of a model which suggests that early life stress dysregulates the
      hypothalamic-pituitary-adrenal axis and increases the likelihood of later life
      risk-taking behaviour. The findings have implications in terms of improving our
      understanding of psychobiological factors which predispose individuals to engage
      in adverse sexual health behaviours.

PMID- 25750780
TI  - "At 150 kg, you can't run" men's weight loss stories in a popular health magazine
      provide appropriate examples of good health practice.
AB  - We explore weight loss stories from 47 men collected from the Australian edition
      of Men's Health magazine between January 2009 and December 2012. Our analysis
      uses a mixed methods approach that combines thematic analysis and descriptive
      statistics to examine weight loss strategies against clinical practice guidelines
      for the management of overweight and obesity. All the stories reported the use of
      physical activity for weight loss and most stories detailed dietary changes for
      weight loss. Our findings indicate that most of the men reportedly used some form
      of behavioural strategies to assist them in their behaviour change efforts. The
      weight loss methods used were consistent with clinical practice guidelines, with
      the exception of some dietary practices. As narratives may assist with behaviour
      change, stories like those examined in this study could prove to be very useful
      in promoting weight loss to men.

PMID- 25750781
TI  - Benefit finding in response to general life stress: measurement and correlates.
AB  - Benefit finding herein defined as "the process of deriving positive growth from
      adversity" has become a key construct in the evolution of positive psychology,
      and research suggests that it may provide the basis for a resource model of
      stress and coping. However, measures of benefit finding have tended to be domain
      specific. The current study focused on developing a more generic multidimensional
      measure of benefit finding. A measure of benefit finding was developed and tested
      in 855 students (574 females and 281 males) aged between 18 and 40 years. A 28
      item scale with six dimensions was produced and Confirmatory Factor Analysis
      (CFA) confirmed the scale structure. The model proposed that psychological and
      social resources would mediate the relationship between experienced stressors and
      benefit finding. Structural equation modelling with Analysis of Moment Structures
      (AMOS) shows that the model is a good fit for the data and psychological and
      social resources partially mediated the relationship. It is argued that
      psychological and social resources enable benefit finding in relation to life
      stress and provide a focus for the development of preventive interventions to
      improve positive health.

PMID- 25750782
TI  - Predictors of colonoscopy use one year after colonoscopy: prospective study of
      surveillance behavior for colorectal cancer.
AB  - We hypothesized that perceived risk of colorectal cancer (CRC) and CRC worry
      would be the main predictors of surveillance behavior in patients undergoing
      colonoscopy. We therefore assessed factors predicting colonoscopy use for re
      examination one year after colonoscopy. Patients who had undergone colonoscopy
      and were scheduled for re-examination one year later were recruited. Patients
      were administered questionnaires after baseline colonoscopy assessing demographic
      factors, perceived risk, CRC worry, cancer preventability, knowledge of CRC and
      results of colonoscopy. We confirmed whether participants underwent colonoscopy
      re-examinations one year later (follow-up). Finally, 56 participants completed
      the research and were used in the final analysis (response rate = 65.1%). We
      found that 37.5% of the participants who underwent baseline colonoscopy underwent
      follow-up colonoscopy one year later. Follow-up colonoscopy was not significantly
      associated with any psychological variables, but was significantly associated
      with educational status (postsecondary) (odds ratio [OR] = 7.10, 95% confidence
      interval [CI] = 1.83-27.56) and the results of baseline colonoscopy in patients
      who did not undergo polypectomy but had remaining polyps (OR = 4.26, 95% CI =
      1.02-17.84). Additionally, significant differences in cancer threat-related
      variables were observed among groups of patients who, during baseline
      colonoscopy, underwent polypectomy but had no remaining polyps, had polyps
      removed with some polyps remaining, or did not undergo polypectomy but had
      remaining polyps (p < .05), with the latter group having a significant
      relationship with repeat colonoscopy. Cancer threat-related variables were not
      predictive of repeat colonoscopy after one year. In contrast, patient educational
      status and the colonoscopy results were predictors. We also found a non-linear
      relationship between high CRC threat and inhibition of the screening behavior in
      that the CRC threat functions as motivation for the surveillance behavior of
      colonoscopy.

PMID- 25750783
TI  - Vulnerability to unhealthy behaviours across different age groups in Swedish
      Adolescents: a cross-sectional study.
AB  - Purpose: There is lack of evidence on the effects of health-promoting programmes
      among adolescents. Health behaviour models and studies seldom compare the
      underlying factors of unhealthy behaviours between different adolescent age
      groups. The main objective of this study was to investigate factors including
      sociodemographic parameters that were associated with vulnerability to health
      damaging behaviours and non-adoption of health-enhancing behaviours in different
      adolescent age groups. Methods: A survey was conducted among 10,590 pupils in the
      age groups of 13-14, 15-16 and 17-18 years. Structural equation modelling was
      performed to determine whether health-damaging behaviours (smoking and alcohol
      consumption) and non-adoption of health-enhancing behaviours (regular meal habits
      and physical activity) shared an underlying vulnerability. This method was also
      used to determine whether gender and socio-economic status were associated with
      an underlying vulnerability to unhealthy behaviours. Results: The findings gave
      rise to three models, which may reflect the underlying vulnerability to health
      damaging behaviours and non-adoption of health-enhancing behaviours at different
      ages during adolescence. The four behaviours shared what was interpreted as an
      underlying vulnerability in the 15-16-year-old age group. In the youngest group,
      all behaviours except for non-participation in physical activity shared an
      underlying vulnerability. Similarly, alcohol consumption did not form part of the
      underlying vulnerability in the oldest group. Lower socio-economic status was
      associated with an underlying vulnerability in all the age groups; female gender
      was associated with vulnerability in the youngest adolescents and male gender
      among the oldest adolescents. Conclusions: These results suggest that
      intervention studies should investigate the benefits of health-promoting
      programmes designed to prevent health-damaging behaviours and promote health
      enhancing behaviours in adolescents of different ages. Future studies should
      examine other factors that may contribute to the underlying vulnerability in
      different age groups.

PMID- 25750784
TI  - Improving predictive accuracy of a survey measure of risk for narcolepsy.
AB  - Narcolepsy is a brain disorder that may go unrecognized and untreated for many
      years. The ability to use easily obtained survey information about symptoms of
      narcolepsy would facilitate identification of individuals potentially at risk for
      narcolepsy who could be referred for further testing. The purpose of the present
      study was to explore whether a survey instrument could successfully distinguish
      narcolepsy from other sleep disorders using data that could easily be obtained
      from a community or general patient sample. The hypothesized model added the
      Epworth Sleepiness Scale to a narcolepsy symptoms checklist to explore whether it
      improved accuracy of classification. Data related to symptoms were extracted from
      medical records of patients with a known diagnosis of narcolepsy, obstructive
      sleep apnea, or insomnia. The sample was then randomly split in half, allowing
      exploratory and confirmatory binary logistic regression. Adding the Epworth
      Sleepiness Scale score to the original list of symptoms more accurately
      classified those with or without narcolepsy. Although these findings require
      additional testing before they can be confirmed and generalized, they suggest
      that a self-report screening instrument for narcolepsy with acceptable accuracy
      is possible.

PMID- 25750785
TI  - Confirmatory factor analysis for two questionnaires of caregiving in eating
      disorders.
AB  - Objective: Caring for someone diagnosed with an eating disorder (ED) is
      associated with a high level of burden and psychological distress which can
      inadvertently contribute to the maintenance of the illness. The Eating Disorders
      Symptom Impact Scale (EDSIS) and Accommodation and Enabling Scale for Eating
      Disorders (AESED) are self-report scales to assess elements of caregiving
      theorised to contribute to the maintenance of an ED. Further validation and
      confirmation of the factor structures for these scales are necessary for rigorous
      evaluation of complex interventions which target these modifiable elements of
      caregiving. Method: EDSIS and AESED data from 268 carers of people with anorexia
      nervosa (AN), recruited from consecutive admissions to 15 UK inpatient or day
      patient hospital units, were subjected to confirmatory factor analysis to test
      model fit by applying the existing factor structures: (a) four-factor structure
      for the EDSIS and (b) five-factor structure for the AESED. Results: Confirmatory
      factor analytic results support the existing four-factor and five-factor
      structures for the EDSIS and the AESED, respectively. Discussion: The present
      findings provide further validation of the EDSIS and the AESED as tools to assess
      modifiable elements of caregiving for someone with an ED.

PMID- 25750786
TI  - Psychometric properties of the forensic inpatient quality of life questionnaire:
      quality of life assessment for long-term forensic psychiatric care.
AB  - A substantial group of forensic psychiatric patients require (life)long forensic
      psychiatric care. Instead of aiming at re-entry into society, treatment in long
      term forensic psychiatric care (LFPC) is principally aimed at medical and
      psychiatric care and optimising quality of life (QoL). To assess QoL in LFPC, the
      influence of both the mental disorder and the restrictive context should be
      considered. Therefore, a new instrument was developed: the Forensic inpatient QoL
      questionnaire (FQL). The FQL is based on the results of concept-mapping with
      patients and staff within LFPC. The main purpose of this study is to evaluate the
      psychometric properties of the FQL. One hundred and sixty-three FQLs, filled out
      by 98 male long-term forensic psychiatric patients, were included for testing
      reliability and content validity. For testing construct validity, 53 patients
      additionally completed the World Health Organisation Quality of Life-Brief
      version and 50 of them the Affect Balance Scale. Outcomes indicate that the FQL
      has good psychometric properties. Fifteen of the 16 FQL domains showed adequate
      to good reliability (Cronbach's alpha range .69-.91) and 9 domains met the
      criteria for homogeneity. Content validity was demonstrated by exploratory factor
      analysis, which revealed a three-factor structure: social well-being, physical
      well-being and leave. Construct validity was supported by 59% correctly
      hypothesised inter- and intrascale Pearson's correlation coefficients. Good
      psychometric properties and its clinical-based development make the FQL a valid
      and useful instrument for QoL assessment in LFPC. The FQL could therefore
      contribute to evidence-based and more advanced treatment programmes in LFPC.

PMID- 25750787
TI  - The spiritual health of veterans with a history of suicide ideation.
AB  - Introduction: In recent years, considerable empirical attention has been devoted
      to examining the increased risk of suicide observed in some Veteran populations.
      This has led to a renewed focus on developing novel support options which can be
      used to respond to Veterans in distress, reducing their risk of suicide.
      Spirituality and religion, however, have been largely absent from any public
      discourse related to suicide prevention, not least of all in Veteran populations.
      Aim: The aim of this cross-sectional study is to compare the self-rated spiritual
      health of Veterans with and without suicide ideation. Identifying differences
      which may exist between these two groups could highlight the relevance of
      spiritual well-being to Veteran suicide prevention efforts. Materials and
      Methods: Data were collected using pencil-and-paper surveys, called Spiritual
      Assessments, distributed within the general population of in- and outpatients at
      a U.S. Department of Veterans Affairs Medical Center. Using Likert-type scales,
      this study examines the self-rated spiritual health, spiritual devotion, and
      significance ascribed to spirituality in a sample of 5378 Veterans. Statistical
      analysis took place using chi-squared to examine differences in the distribution
      of responses between ideators and non-ideators. Results: Ideators significantly
      more often rated their spiritual health as worse than that of non-ideators. Even
      with similar levels of spiritual devotion or significance ascribed to spiritual
      life, ideators continued to significantly more often rate their spiritual health
      as worse than that of non-ideators. Conclusion: The results show that Veterans
      with suicide ideation more often rate their spiritual health as worse than that
      of Veterans without suicide ideation. This suggests that spiritual well-being may
      indeed be relevant to suicide prevention efforts in Veteran populations.

PMID- 25750788
TI  - An evaluation of public, private, and mobile health clinic usage for children
      under age 5 in Aceh after the tsunami: implications for future disasters.
AB  - Background: Aceh, Indonesia, was the hardest-hit area in the 26 December 2004
      Indian Ocean earthquake and tsunami, with more than 500,000 people displaced,
      120,000 people dead, and total damages and losses estimated at $4.5 billion. The
      relief effort following the tsunami was also immense. Objectives: This study
      aimed to determine and assess utilization patterns of formal public versus
      private and mobile health services for children under age 5 with diarrhea, cough
      and difficulty breathing, fever, or skin disease and to identify determinants of
      care usage. Methods: A household survey of 962 households was administered to
      caretakers of children aged 1-5 years. A sample of clusters within Banda Aceh and
      Aceh Besar were selected and those caretakers within the cluster who fit the
      inclusion criteria were interviewed. Results: Of those caretakers who utilized
      formal health services as the first line of care for their sick child, 62% used a
      public health facility, 30% used a private health facility, and 8% used a mobile
      clinic. In terms of significant factors associated with public, private, and
      mobile care utilization, mobile clinics were at one side of the spectrum and
      private clinics were at the other side overall, with public care somewhere in
      between. This was true for several variables. Mobile clinic users reported the
      lowest cost of services and medicine and the highest perceived level of
      accessibility, and private care users reported the highest perceived level of
      satisfaction. Conclusions: Utilization of formal health services for children was
      quite high after the tsunami. The caretaker's perceived satisfaction with public
      health services could have been improved. Mobile clinics were an accessible
      source of health care and could be used in future disaster relief efforts to
      target those populations that seek less care for their sick children, including
      displaced populations, and those children whose parents have died.

PMID- 25750789
TI  - A process-oriented measure of habit strength for moderate-to-vigorous physical
      activity.
AB  - Purpose: Habitual action is an important aspect of health behaviour, but the
      relevance of various habit strength indicators continues to be debated. This
      study focused specifically on moderate-to-vigorous physical activity (MVPA) and
      evaluated the construct validity of a framework emphasizing patterned action,
      stimulus-response bonding, automaticity, and negative consequences for
      nonperformance as indicators of habit strength for this form of exercise.
      Methods: Upper-level undergraduates (N = 124) provided demographic information
      and responded to questionnaire items assessing historical MVPA involvement,
      current MVPA involvement, and the four proposed habit strength dimensions. Factor
      analyses were used to examine the latent structure of the habit strength
      indicators, and the model's construct validity was evaluated via an examination
      of relationships with repetition history and current behaviour. Results: At a
      measurement level, findings indicated that the proposed four-component model
      possessed psychometric integrity as a coherent set of factors. Criterion-related
      validity was also demonstrated via significant changes in three of the four
      factors as a function of past involvement in MVPA and significant correlations
      with the frequency, duration, and intensity of current MVPA. Conclusions: These
      findings support the construct validity of this exercise habit strength model and
      suggest that it could provide a template for future research on how MVPA habits
      are developed and maintained.

PMID- 25750790
TI  - Life stress as a determinant of emotional well-being: development and validation
      of a Spanish-Language Checklist of Stressful Life Events.
AB  - Objectives: To develop a screening instrument for investigating the prevalence
      and impact of stressful life events in Spanish-speaking Peruvian adults.
      Background: Researchers have demonstrated the causal connection between life
      stress and psychosocial and physical complaints. The need for contextually
      relevant and updated instruments has been also addressed. Methods: A sequential
      exploratory design combined qualitative and quantitative information from two
      studies: first, the content validity of 20 severe stressors (N = 46); then, a
      criterion-related validity process with affective symptoms as criteria (Hopkins
      Symptom Checklist (HSCL-25), N = 844). Results: 93% of the participants reported
      one to eight life events (X = 3.93, Mdn = 3, SD = 7.77). Events increase
      significantly until 60 years of age (Mdn = 6). Adults born in inland regions (Mdn
      = 4) or with secondary or technical education (Mdn = 5) reported significantly
      more stressors than participants born in Lima or with higher education. There are
      no differences by gender. Four-step hierarchical models showed that life stress
      is the best unique predictor (beta) of HSCL anxiety, depression and general
      distress (p < .001). Age and gender are significant for the three criteria (p <
      .01, p < .001); lower education and unemployment are significant unique
      predictors of general distress and depression (p < .01; p < .05). Previously, the
      two-factor structure of the HSCL-25 was verified (Satorra-Bentler chi-square,
      root-mean-square error of approximation = 0.059; standardized root-mean-square
      residual = 0.055). Conclusion: The Spanish-Language Checklist of Stressful Life
      Events is a valid instrument to identify adults with significant levels of life
      stress and possible risk for mental and physical health (clinical utility).

PMID- 25750791
TI  - Measuring age-specific variations in income-related inequalities in smoking
      behavior in Germany.
AB  - Although monitoring smoking behavior is considered as most important to tackle
      the smoking epidemic, empirical evidence concerning age-specific variations of
      its income-related inequalities still seems scarce. This paper uses a
      semiparametric extension of the concentration index to measure age-specific
      variations of income-related inequalities in smoking behavior. First, current
      smoking is used to describe peoples' actual smoking status. Second, ever-smoking
      is included to approximate how inequalities in smoking behavior changed with the
      evolution of the smoking epidemic. Finally, smoking cessation is considered to
      indicate an individual's ability to conquer the habit. Cross-sectional data from
      the 2009 survey of the German microcensus reveal that current smoking is most
      prevalent among adolescents and young adults, more common among the worse-off in
      younger age groups and concentrated among the better-off in older age groups.
      Concentration of ever-smoking among the economically deprived is only found for
      younger adults. Smoking cessation is more common among higher income ever-smokers
      in all age groups. One may deduce from these results that anti-smoking policies
      should particularly aim at younger individuals in lower-income households.

PMID- 25750792
TI  - Predicting Internet risks: a longitudinal panel study of gratifications-sought,
      Internet addiction symptoms, and social media use among children and adolescents.
AB  - This study used longitudinal panel survey data collected from 417 adolescents at
      2 points in time 1 year apart. It examined relationships between Internet risks
      changes in Time 2 and social media gratifications-sought, Internet addiction
      symptoms, and social media use all measured at Time 1. By controlling for age,
      gender, education, and criterion variable scores in Internet addiction at Time 1,
      entertainment and instant messaging use at Time 1 significantly predicted
      increased Internet addiction measured at Time 2. The study also controlled for
      demographics and scores of criterion variables in Internet risks: targeted for
      harassment, privacy exposed, and pornographic or violent content consumed in Time
      1. Gratifications-sought (including status-gaining, expressing opinions, and
      identity experimentation), Internet addiction symptoms (including withdrawal and
      negative life consequences), and social media use (in particular, blogs, and
      Facebook) significantly predicted Internet risk changes in Time 2. These findings
      suggest that, with their predictive power, these predictors at Time 1 could be
      used to identify those adolescents who are likely to develop Internet addiction
      symptoms and the likelihood of experiencing Internet risks based on their
      previous gratifications-sought, previous addiction symptoms, and their habits of
      social media use at Time 1.

PMID- 25750793
TI  - Reference-dependent preferences for maternity wards: an exploration of two
      reference points.
AB  - It is now well established that a person's valuation of the benefit from an
      outcome of a decision is determined by the intrinsic "consumption utility" of the
      outcome itself and also by the relation of the outcome to some reference point.
      The most notable expression of such reference-dependent preferences is loss
      aversion. What precisely this reference point is, however, is less clear. This
      paper claims and provides empirical evidence for the existence of more than one
      reference point. Using a discrete choice experiment in the Israeli public health
      care sector, within a sample of 219 women who had given birth, it is shown that
      respondents refer to two reference points: (i) a constant scenario that is used
      in the experiment; and (ii) also the actual state of the quantitative attributes
      of the service (number of beds in room of hospitalization; and travel time from
      residence to hospital). In line with the loss aversion theory, it is also shown
      that losses (vis-a-vis the constant scenario and vis-a-vis the actual state)
      accumulate and have reinforced effects, while gains do not.

PMID- 25750794
TI  - The prevalence of musculoskeletal pain and use of painkillers among adolescent
      male ice hockey players in Finland.
AB  - Participating in competitive sport increases the risk for injuries and
      musculoskeletal pain among adolescent athletes. There is also evidence that the
      use of prescription drugs has increased among sport club athletes. The purpose of
      this study was to evaluate the use of painkillers among young male ice hockey
      players (IHP) in comparison to schoolboys (controls) and its relation to the
      prevalence of musculoskeletal pain and problems during activities and sleeping.
      Information was gathered through a questionnaire, completed by 121 IHP and
      compared to the responses of 618 age-matched controls. Results showed that
      monthly existing pain was at 82% for IHP, and 72% for controls, though IHP had
      statistically more musculoskeletal pain in their lower limbs (56% vs. 44%), lower
      back (54% vs. 35%), and buttocks (26% vs. 11%). There were no group differences
      in the neck, upper back, upper limb, or chest areas. The disability index was
      statistically similar for both groups, as musculoskeletal pain causing
      difficulties in daily activities and sleeping was reported by a minority of
      subjects. Despite this similarity, IHP used more painkillers than controls (18%
      vs. 10%). Further nuanced research is encouraged to compare athletes and non
      athletes in relation to painkillers.

PMID- 25750795
TI  - Systematic literature review of Internet interventions across health behaviors.
AB  - Purpose: This review examines Internet interventions aiming to change health
      behaviors in the general population. Methods: Internet health interventions in
      the USA published between January 2005 and December 2013 were identified through
      Medline and CINAHL. Keywords used were (Internet or e-health or social media or
      web) paired with (intervention or program*). A total of 38 articles met all
      criteria and were reviewed. Results: Studies were analyzed by targeted health
      behavior interventions: tobacco (5), alcohol (4), weight loss (7), physical
      activity (PA) (7), nutrition (2), PA and nutrition combined (5), HIV or sexual
      health (4), and chronic diseases (4). Interventions ranged from one session to 24
      weeks (average 6-12 weeks). Common strategies used, including web-based
      information, tailored feedback, weekly e-mails, goal setting, and self
      assessment. Social cognitive theory and the transtheoretical models were the most
      commonly used frameworks. Recruitment strategies were typically media based
      varied by settings and populations. Except for the tobacco interventions, the
      majority studies yielded significant outcomes. Conclusion: This review provides
      updates and synthesized knowledge on the design and consistent effectiveness of
      Internet interventions across health behaviors. Results have implications for
      public health and healthcare professionals, as they play a key role in developing
      and delivering health promotion interventions as well as in assisting the
      communities and clients serviced obtaining evidence-based health information.

PMID- 25750796
TI  - Strategies for improving the quality of verbal patient and family education: a
      review of the literature and creation of the EDUCATE model.
AB  - Objective: Patient and family education includes print, audio-visual methods,
      demonstration, and verbal instruction. Our objective was to study verbal
      instruction as a component of patient and family education and make
      recommendations for best practices for healthcare providers who use this method.
      Methods: We conducted a literature review of articles from 1990 to 2014 about
      verbal education and collaborated on departmental presentations to determine best
      practices. A survey was sent to all nursing staff to determine perceptions of
      verbal education and barriers to learning. Results: Through our work, we were
      able to identify verbal education models, best practices, and needs. We then
      constructed the EDUCATE model of verbal education, which built upon our findings.
      Conclusion: Verbal education of patients and family members requires a
      multidisciplinary approach that takes into account learning styles, literacy, and
      culture to apply clear communication and methods for the assessment of learning.
      Providers need the skills, time, and training to effectively perform patient and
      family verbal education every time they care for patients. Further research needs
      to be performed on how to test, document, and quantify patients' comprehension
      and retention of verbal instructions.

PMID- 25750797
TI  - Physical function and quality of well-being in fibromyalgia: the applicability of
      the goodness-of-fit hypothesis.
AB  - Objective: The goodness-of-fit hypothesis suggests that the effectiveness of a
      coping strategy depends on the match between type of strategy (problem-focused,
      emotion-focused) and the level of perceived control. This hypothesis was examined
      as a predictor of physical functioning and quality of well-being (QWB) in a large
      sample of women with fibromyalgia. Methods: Participants were 478 women with
      diagnosed fibromyalgia (Mage = 54.31, SD = 11.2), who were part of a larger
      intervention in which no intervention effects were found. Hierarchical, mixed
      selection regressions were performed to determine whether the relationship
      between coping and control-predicted physical functioning and QWB. Results:
      Participants who reported having lower levels of perceived control over their
      fibromyalgia syndrome and who engaged in more self-controlling coping (emotion
      focused strategy) experienced greater QWB and physical functioning than those who
      used less self-controlling coping. Various main effects for coping and perceived
      control were also found. Level of physical functioning was also related to escape
      avoidance, distancing, and perceived control. The level of QWB was related to
      social-support seeking, accepting responsibility, distancing, problem-solving,
      and perceived control. Conclusions: This study provides a greater understanding
      of the relationships among coping, perceived control, physical functioning, and
      well-being for women with fibromyalgia. Implications and directions for future
      research are discussed.

PMID- 25750798
TI  - COMT and 5-HT1A-receptor genotypes potentially affect executive functions
      improvement after cognitive remediation in schizophrenia.
AB  - Cognitive remediation therapy (CRT) has been proved to improve cognitive deficits
      in schizophrenia and to enhance functional outcomes of classical rehabilitation.
      However, CRT outcomes are heterogeneous and predictors of response are still
      unknown. Genetic variability, especially in the dopaminergic system, has been
      hypothesized to affect CRT. We previously reported that rs4680 of the catechol-O
      methyltrasferase (COMT) influences improvements in executive functions in
      patients treated with CRT, but this result was not confirmed by other studies.
      Such inconsistent findings may depend, other than on clinical variables, also on
      other genes involved in cognition. Recent studies proved that serotonin 1A
      receptor (5-HT1A-R) regulates dopamine in the prefrontal cortex (PFC), and
      clinical works suggested a 5-HT1A-R role in cognition. We then analysed possible
      effects of COMT rs4680 and 5-HT1A-R rs6295 on CRT outcomes, taking into account
      also clinical and demographic factors. Eighty-six clinically stabilized
      schizophrenia patients treated with three months CRT were assessed with the
      Wisconsin Card Sorting Test, as a measure of executive functions, at enrolment
      and after CRT treatment, and underwent COMT and 5-HT1A-R genotyping. We found a
      significant main effect of COMT genotype and an interaction with 5-HT1A-R on
      executive function improvement after CRT. The results suggest that these two
      polymorphisms may have an additive effect on individual capacity to recover from
      cognitive deficit, probably through their role on PFC dopaminergic transmission
      modulation, known to be critical for modulating cognitive functions.

PMID- 25750799
TI  - Trauma-related obsessive-compulsive disorder: a review.
AB  - Obsessive-compulsive disorder (OCD) is a highly researched and conceptualized
      disorder, and yet it remains one of the most debilitating, widespread, and
      expensive disorders one can be afflicted with [Real, E., Labad, J., Alonso, P.,
      Segalas, C., Jimenez-Murcia, S., Bueno, B., ... Menchon, J. M. (2011). Stressful
      life events at onset of obsessive-compulsive disorder are associated with a
      distinct clinical pattern. Depression and Anxiety, 28, 367-376.
      doi:10.1002/da.20792]. Exposure treatments and cognitive-behavioural therapy
      (CBT) have been largely accepted as best practice for those with OCD, and yet
      there are still many who are left with "treatment-resistant OCD" [Rowa, K.,
      Antony, M., & Swinson, R. (2007). Exposure and response prevention. In C. Purdon,
      M. Antony, & L. J. Summerfeldt (Eds.), Psychological treatment of obsessive
      compulsive disorder: Fundamentals and beyond (pp. 79-109). Washington, DC:
      American Psychological Association; Foa, E. B. (2010). Cognitive behavioural
      therapy of obsessive-compulsive disorder. Dialogues of Clinical Neuroscience, 12,
      199-207]. Similarly, exposure treatments and CBT have been accepted as best
      practice for trauma-related distress (i.e. post-traumatic stress disorder; Foa,
      E. B., Keane, T. M., Friedman, M. J., & Cohen, J. A. (2009). Effective treatments
      for PTSD: Practice guidelines from the international society for traumatic
      studies (2nd ed.). New York, NY: The Guilford Press). From a literature review,
      evidence has been provided that demonstrates a high prevalence rate (30-82%) of
      OCD among individuals with a traumatic history in comparison to the prevalence
      rate of the general population (1.1-1.8%; [Cromer, K. R., Schmidt, N. B., &
      Murphy, D. L. (2006). An investigation of traumatic life events and obsessive
      compulsive disorder. Behaviour Research and Therapy, 45, 1683-1691.
      doi:10.1016/j.brat.2006.08.018; Fontenelle, L. F., Cocchi, L., Harrison, B. J.,
      Shavitt, R. G., do Rosario, M. C., Ferrao, Y. A., ... Torres, A. R. (2012).
      Towards a post-traumatic subtype of obsessive-compulsive disorder. Journal of
      Anxiety Disorders, 26, 377-383. doi:10.1016/j.janxdis.2011.12.001; Gershuny, B.
      S., Baer, L., Parker, H., Gentes, E. L., Infield, A. L., & Jenike, M. A. (2008).
      Trauma and posttraumatic stress disorder in treatment-resistant obsessive
      compulsive disorder. Depression and Anxiety, 25, 69-71. doi:10.1002/da.20284]).
      Evidence was collected for a post-traumatic OCD and treatments of trauma-related
      OCD were considered. OCD and traumatic histories have a significant enough
      overlap that trauma should be a consideration when treating an individual with
      OCD. Given the overlap of the client base with OCD and traumatic histories, as
      well as the overlap in treatment options for those who experience OCD and trauma
      induced symptoms, the author will discuss the importance of assessing for
      traumatic history in clients with OCD as well as approaching treatment from a
      dual-focus orientation.

PMID- 25750800
TI  - A bifactor model of the Posttraumatic Growth Inventory.
AB  - Purpose: The Posttraumatic Growth Inventory (PTGI) is a self-administered
      measurement instrument designed to provide information concerning positive
      psychological changes after a traumatic life event. The aim of the present study
      was to examine the psychometric properties of the PTGI in a Hungarian sample. By
      examining a bifactor model of the instrument, we also wanted to contribute to the
      establishment of an evidence-based practice concerning the use of different score
      types (total score versus subscale scores). Methods: Altogether, 691 Hungarian
      respondents (82.2% female; Mage = 33.0 +/- 13.4 years), who experienced some kind
      of trauma or loss, participated in this study. Results: A series of confirmatory
      factor analyses revealed that among the tested first- and second-order models, a
      bifactor model provided the best-fit to our data (chi2/df = 4.32, Comparative Fit
      Index = .91, root mean square error of approximation = .07, standardized root
      mean square residual = .04). Further, the Hungarian version of the PTGI showed
      high internal consistency (Cronbach's alpha = .93, omega total = .95, omega
      hierarchical = .87) and test-retest reliability (r = .90; p < .01) coefficients.
      However, omega hierarchical coefficients (.14-.40) and explained variance values
      (.05-.10) for the subscales were low. Conclusions: The present study provided
      empirical support for the psychometric adequacy of the Hungarian adaptation of
      the PTGI and suggests that only the total and not the subscale scores of the
      inventory should be used.

PMID- 25750801
TI  - Research conducted on Caribbean women's perceived human immunodeficiency virus
      risks: A narrative review and methodological critique.
AB  - Background: Caribbean women have the highest human immunodeficiency virus (HIV)
      infection rates among women in the Americas; however, their self-assessment of
      HIV risk is alarmingly low. This reflects a low perceived risk for HIV. English
      speaking Caribbean countries are typically understudied in this area. It is
      important for health researchers and practitioners to understand the underlying
      perceptions of women who are now driving this epidemic. This review discusses and
      critiques the published literature that examines Caribbean women's perceived HIV
      risks. Methods: Medline, PsycINFO, Global Health, Women's Studies International,
      and Academic Search Complete databases were searched using various combinations
      of the following keywords: Caribbean, women, HIV, STD, AIDS, risk, perceived
      risk, risk perception, and sex. Searches were restricted to English. A total of
      69 peer-reviewed studies were obtained from the initial 239 records. The reviewer
      screened the peer-reviewed articles and excluded 50 studies that did not directly
      assess perceived HIV risks in Caribbean women. An additional 12 studies were
      excluded based on the following exclusion criteria: an undetermined proportion or
      more than 50% of the sample consisted of pregnant women, sex workers, drug users,
      Latinas, and/or people living with HIV/AIDS. Results: Seven studies on perceived
      HIV risk in Caribbean women were reviewed. Jamaican women were the most
      represented ethnic demographic (43%). All studies assessed perceived risk as a
      subset of HIV psychosocial factors, sexual-risk behaviors, HIV knowledge,
      attitudes, and beliefs. Four studies used cross-sectional research design and two
      studies used qualitative methodology. Only one study described items used to
      measure perceived risk. General findings indicate overall perceptions of
      invulnerability among Caribbean women, despite high sexual-risk behaviors.
      Conclusions: Published studies that specifically assess Caribbean women's HIV
      risk perceptions are currently lacking. Qualitative research is needed to further
      evaluate and explore perceived risks. This will better inform practical
      strategies that can enable women to discern between their perceived and actual
      risks, and invariably reduce sexual risk-taking behaviors.

PMID- 25750802
TI  - Disseminating skills to carers of people with eating disorders: an examination of
      treatment fidelity in lay and professional carer coaches.
AB  - Family members of people with eating disorders (EDs) have high levels of stress
      and can use maladaptive methods of coping. We have developed an intervention,
      using motivational interviewing (MI) strategies that trains lay and professional
      carer coaches (CCs) to support carers of adolescents with EDs to use more
      adaptive coping procedures. The aim of this study is to measure treatment
      integrity in coaches with either academic or lived experience. Eleven coaches
      were trained and supervised by an expert trainer and an 'expert by experience'
      trainer. Six of the coaches had prior training in clinical work and/or psychology
      and five had personal experience of supporting a loved one with an ED. Two audio
      taped sessions (Sessions 3 and 7) from each family coached (n = 22) were assessed
      for fidelity to MI. Half the sessions (50% n = 11) had a Motivational
      Interviewing Treatment Integrity global score above the suggested cut-off for
      recommended competency. Prior clinical training was related to higher treatment
      fidelity and experiential training (having coached a greater number of families)
      improved treatment fidelity in the lay carer group. These preliminary findings
      suggest that: "lay CCs" can be trained to deliver an intervention based on MI.
      Further exploration of a more effective means of training, monitoring and
      supervision is required to maximise the quality of the intervention.

PMID- 25750803
TI  - Autonomous and controlled motivational regulations for multiple health-related
      behaviors: between- and within-participants analyses.
AB  - Self-determination theory has been applied to the prediction of a number of
      health-related behaviors with self-determined or autonomous forms of motivation
      generally more effective in predicting health behavior than non-self-determined
      or controlled forms. Research has been confined to examining the motivational
      predictors in single health behaviors rather than comparing effects across
      multiple behaviors. The present study addressed this gap in the literature by
      testing the relative contribution of autonomous and controlling motivation to the
      prediction of a large number of health-related behaviors, and examining
      individual differences in self-determined motivation as a moderator of the
      effects of autonomous and controlling motivation on health behavior. Participants
      were undergraduate students (N = 140) who completed measures of autonomous and
      controlled motivational regulations and behavioral intention for 20 health
      related behaviors at an initial occasion with follow-up behavioral measures taken
      four weeks later. Path analysis was used to test a process model for each
      behavior in which motivational regulations predicted behavior mediated by
      intentions. Some minor idiosyncratic findings aside, between-participants
      analyses revealed significant effects for autonomous motivational regulations on
      intentions and behavior across the 20 behaviors. Effects for controlled
      motivation on intentions and behavior were relatively modest by comparison.
      Intentions mediated the effect of autonomous motivation on behavior. Within
      participants analyses were used to segregate the sample into individuals who
      based their intentions on autonomous motivation (autonomy-oriented) and
      controlled motivation (control-oriented). Replicating the between-participants
      path analyses for the process model in the autonomy- and control-oriented samples
      did not alter the relative effects of the motivational orientations on intention
      and behavior. Results provide evidence for consistent effects of autonomous
      motivation on intentions and behavior across multiple health-related behaviors
      with little evidence of moderation by individual differences. Findings have
      implications for the generalizability of proposed effects in self-determination
      theory and intentions as a mediator of distal motivational factors on health
      related behavior.

PMID- 25750804
TI  - Mortality among long-stay patients with schizophrenia during the setting-up of
      community facilities under the Yuli model.
AB  - Objective: Over the past 15 years, Yuli Veterans Hospital (YVH) in Taiwan has
      developed the Yuli model to reform long-stay care for psychiatric patients. The
      development of the Yuli model could be divided into pre-early (1998-1999), early
      (2000-2006) and late (2007-2008) periods according to the setting-up of the
      community facilities. In the pre-early period, a vocational rehabilitation
      program was established for psychiatric patients in YVH. In the later periods,
      the independent living skills training and the program for social reintegration
      were instituted in the community facilities. This study aimed to evaluate
      mortality among the long-stay patients with schizophrenia during the three
      periods. Methods: In all, 2457 patients with schizophrenia who had been
      hospitalized for at least one year initially were retrospectively followed from 1
      January 1998 to 31 December 2008. Compared with the general population in Taiwan,
      we calculated the age- and sex-specific standardized mortality ratios (SMRs) of
      those patients by cause of death during the three periods. Results: Most of the
      patients were male (81.3%). The mean +/- SD age of the patients was 57.83 +/-
      16.95 years. The all-, natural- and unnatural-cause mortalities of the patients
      were nearly two times greater than those of the general population during the
      whole study period. Compared with those in the pre-early and early periods, all
      patients in the late period had the lowest mortality gaps. In the pre-early,
      early and late periods, the all-cause SMR were 5.40 (95% confidence interval (CI)
      = 4.27-6.81), 2.90 (95% CI = 2.20-3.79) and 1.17 (95% CI = 0.54-2.22),
      respectively, for the 50-69-year-old male patients. Nearly half of all the
      patients who participated the whole comprehensive rehabilitation program belonged
      to this sex and age group (N = 156, 46.6%). Conclusions: With the setting-up of
      community facilities for the comprehensive rehabilitation program, the mortality
      gaps among the 50-69-year-old male patients apparently decreased using the Yuli
      model.

PMID- 25750805
TI  - Urbanisation and sexual health: understanding bisexually active men in Hanoi,
      Vietnam.
AB  - Background: Men who have sex with men (MSM) in Vietnam are receiving increased
      attention in recognition of their high-risk behaviours and potential for human
      immunodeficiency virus (HIV) infection and transmission. Due to societal
      pressures, many MSM in Vietnam are also bisexually active, which ultimately
      increases the transmission risks beyond the MSM population. Evidence is emerging
      that indicates a greater proportion of women in Asia with low-risk sexual
      activities are contracting HIV from their male partners who have become HIV
      infected through male-male sex. Methodology: Fourteen focus group discussions
      exploring sexual and social networks were conducted in Hanoi between July 2010
      and September 2010. A total of 96 individuals participated in these sessions.
      Findings: A risk environment approach was used to analyse the focus group themes
      of social stigma and marriage, sex with other men in closed settings and
      transactional sex in Hanoi, an increasingly urbanising and westernising city.
      Implications: Despite limited evidence globally that bisexual men act as a bridge
      for sexually transmitted diseases, there is particular concern in Vietnam about
      this potential risk. HIV rates amongst MSM are rapidly rising and there are
      reports of women contracting HIV from their male partners who are bisexually
      active.

PMID- 25750806
TI  - Indonesian experts' perspectives on a curriculum for psychologists working in
      primary health care in Indonesia.
AB  - Mental health is a critical issue in Indonesia, since its population ranks among
      the top five in the world and the prevalence of common mental disorders is 11.6%
      of the adult population. However, the need to build an effective mental health
      care system that is accessible to the whole population has only been recently
      addressed. The Aceh tsunami in 2004 brought to the forefront an unexpected window
      of opportunity to build a mental health-care system. Integration of mental health
      care into primary health care is a key strategy to close the treatment gap for
      people with mental disorders. Existing integration of psychologists into primary
      health care is a big step to meet the shortage of mental health-care specialists.
      As primary mental health care is an emerging field, the perspectives of
      Indonesian experts on Indonesian mental health care are needed to develop a
      curriculum for training psychologists to work in primary health care. In this
      study, data have been collected through semi-structured interviews with 24
      Indonesian mental health experts, and three focus group discussions with 26
      psychologists. Overall, experts agreed that to be able to work in primary health
      care psychologists should have roles and training ranging from clinical to
      advocacy skills. Participants also agreed that psychologists should work in the
      community and contribute to primary health care as service providers and that
      strong collaborations between psychologists and other primary health-care
      providers are the key; these can be developed partly through referral and by
      respecting each other's unique strengths.

PMID- 25750808
TI  - Collectivism/individualism and its relationship to behavioral and physiological
      immunity.
AB  - The interaction between the behavioral and physiological immune systems provides
      fertile ground for research. Here, we examine the interactions between fear of
      disease, collectivism/individualism, disgust, visual perception and salivary IgA.
      First, we parsed collectivism/individualism into ancestry and psychological
      processes and examined their relationships to fear of disease. Both ancestral and
      psychological collectivists scored higher on a test of hypochondria than
      individualists. Additionally, in two studies we exposed participants to slides of
      diseased, injured or healthy individuals. Diseased and injured stimuli were rated
      as equally disgusting, while diseased stimuli were rated as more disgusting than
      healthy stimuli. We measured salivary IgA in participants before and after they
      viewed the stimuli. Participants provided information on their ancestral
      collectivism or individualism. Salivary IgA levels increased after participants
      viewed images of diseased or injured individuals. Participants with collectivist
      ancestry tended to react to the diseased and injured images with an increase in
      IgA, while levels of IgA remained the same or decreased in individualists in one
      study but we failed to replicate the effect in the second study. An increased
      salivary IgA response to potentially diseased individuals is adaptive, because
      salivary IgA plays an important role in protecting individuals from contracting
      an infection. The response may be related to increased preoccupation with disease
      states.

PMID- 25750807
TI  - Cognitive functioning, depression, and HIV medication adherence in India: a
      randomized pilot trial.
AB  - Objective: India is home to the third-largest number of people living with HIV in
      the world, and no-cost antiretroviral therapy (ART) has been available across the
      country since 2004. However, rates of adherence to ART are often subpar in India,
      and interventions to increase adherence are warranted. Cognitive impairment and
      depression have been associated with ART non-adherence, and may also limit the
      impact of behavioral interventions designed to improve adherence. Studies have
      not evaluated the impact of cognitive impairment and depression on response to
      adherence interventions in India. Methods: Individuals new to ART (<=12 months
      prescribed) were recruited from a public hospital in Chandigarh, India.
      Participants (N = 80) were randomized to either a group medication adherence
      intervention (MAI) or an enhanced standard of care (ESOC) condition. The MAI
      consisted of three monthly gender-concordant group cognitive-behavioral sessions
      addressing HIV and ART, adherence, and HIV-related coping and social support.
      Participants were assessed at baseline for depression and cognitive functioning,
      and assessed monthly for adherence by pill count. Results: Adherence among
      participants receiving the MAI improved by about one day's dose over the course
      of the study, and no improvement was noted among those in the ESOC. Additionally,
      high rates of cognitive impairment (57%) and depression (25%) were identified
      among participants. There was no evidence that cognitive impairment moderated
      response to the intervention. However, while non-depressed participants
      benefitted from the intervention, depressed participants failed to show the same
      improvement. Conclusions: Results of this pilot study suggest that group
      behavioral interventions can be an effective strategy to promote ART adherence in
      this population, even among those demonstrating cognitive impairment. However,
      because of the negative impact of depression on adherence, future studies should
      continue to develop strategies to identify and treat it among people living with
      HIV in India.

PMID- 25750809
TI  - Self-arranged exposure for overcoming blood-injection-injury Phobia: a case
      study.
AB  - Blood-injection-injury (BII) phobia is both common and dangerous, because it can
      lead to avoidance of medical procedures for diagnosis and treatment. It also
      tends to prevent individuals from donating blood for use in the healthcare of
      others. BII phobia often has an unusual characteristic for a type of phobia -
      fainting. The typical treatment for BII phobia involves teaching the client how
      to avoid fainting and staging multiple gradual-exposure trials for the client. In
      this case report, an adult with the phobia obtained initial, mostly written,
      guidance from a psychologist, arranged her own applied muscle-tension practice
      sessions to learn how to keep from fainting, created her own fear hierarchy, and
      staged exposure trials herself, ending years of avoidance of blood withdrawal. By
      the end of the trials, she was able to give blood for a medical test and to
      donate blood for the first time in her life and to work as a volunteer at a blood
      donation center. The results provide the first evidence that adults with BII
      phobia can end the phobia by arranging their own sessions of applied-tension
      practice and gradual self-exposure. The results suggest a new option for treating
      specific phobias in general with some adults: initial professional guidance
      followed by self-arranged gradual-exposure trials.

PMID- 25750810
TI  - Respect in final-year student nurse-patient encounters - an interpretative
      phenomenological analysis.
AB  - Very little is known regarding health-care professionals' understanding and
      experiences of respect towards patients. The study aimed to explore student
      nurses' understanding and experiences of respect in their encounters with
      patients. Semi-structured interviews were conducted with eight final-year student
      nurses with practice placements across different health-care trusts in the UK.
      Transcripts were analysed using interpretative phenomenological analysis (IPA).
      Three super-ordinate themes were identified: understanding of what it means to
      show respect, negotiating role expectations and personal attitudes in practice,
      and barriers related to the performance of the nursing role. The factors
      identified should be investigated further and addressed as they are likely to
      influence patients' experiences of feeling respected in nurse-patient
      interactions and subsequently their well-being and health-related behaviours.

PMID- 25750811
TI  - The relationship between attributional style and destructive responses to job
      dissatisfaction: an exploratory study of internal migrant workers in China.
AB  - This study examines the relationship between attributional style and destructive
      responses to job dissatisfaction among internal migrant workers in mainland
      China. Contrary to previous studies conducted in the West, we found that
      internality of bad events was negatively related to destructive responses to job
      dissatisfaction. Stability and globality were positively related to destructive
      responses to job dissatisfaction. We suggest that the concept of interdependent
      self-construal may explain the unique positive meaning of internality of bad
      events among Chinese migrant workers. The practical significance of the findings
      is discussed.

PMID- 25750812
TI  - "Am I carrier?" The patient's lived experience of thrombophilia genetic screening
      and its outcome.
AB  - How do patients with thrombophilia experience a physician's request to undergo a
      genetic test? How do they experience the test outcome? To answer these questions,
      we conducted an interpretative phenomenological analysis study, based on 10 in
      depth interviews with patients who underwent genetic testing for thrombophilia in
      Italy, half with positive and half with negative results. The experience of
      undergoing genetic screening for thrombophilia plays an important role in
      reconfiguring patients' signification of their illness experience. A positive
      outcome becomes a cue to reorganize in a more adaptive way the illness meaning at
      the cognitive and emotive levels, whereas a negative outcome appears more
      distressing and confusing. As a clinical implication of the study, clinicians
      should consider communicating carefully with the patients regardless from the
      positive/negative test results and they should explore the patient's specific
      reaction and understanding of test result.

PMID- 25750813
TI  - Perceived discrimination, schooling arrangements and psychological adjustments of
      rural-to-urban migrant children in Beijing, China.
AB  - Objectives: The global literature has revealed potential negative impacts of
      migration and discrimination on individual's psychological adjustments. However,
      the psychological adjustments among internal migrant children in developing
      countries are rarely assessed. This study simultaneously examines perceived
      discrimination and schooling arrangements in relation to psychological
      adjustments among rural-to-urban migrant children in China. Methods: A sample of
      657 migrant children was recruited in Beijing, China. Cross-sectional
      associations of self-reported perceived discrimination and schooling arrangements
      (i.e. public school and migrant children school (MCS)) with psychological
      adjustment outcomes (i.e. social anxiety, depression and loneliness) were
      examined by general linear model. Results: (1) Compared with migrant children in
      public school, migrant children in MCS had lower family incomes, and their
      parents had received less education. (2) Migrant children in MCS reported higher
      levels of social anxiety, depression and loneliness than did their counterparts.
      Children who reported high level of perceived discrimination also reported the
      highest level of social anxiety, depression and loneliness. (3) Perceived
      discrimination had main effects on social anxiety and depression after
      controlling for the covariates. A significant interaction between perceived
      discrimination and schooling arrangements on loneliness was found. Specifically,
      the migrant children in MCS reported higher loneliness scores than did migrant
      children in public school only at low level of perceived discrimination; however,
      schooling arrangements was unrelated to loneliness at medium and high levels of
      discrimination. Conclusions: These results indicate that migration-related
      perceived discrimination is negatively associated with migrant children's
      psychological adjustments. These findings suggest that effective interventions
      should be developed to improve migrant children's capacities to cope with
      migration-related discrimination and improve their psychological adjustments,
      especially in terms of loneliness.

PMID- 25750814
TI  - A clustering method to identify who benefits most from the treatment group in
      clinical trials.
AB  - In randomized controlled trials (RCTs), the most compelling need is to determine
      whether the treatment condition was more effective than control. However, it is
      generally recognized that not all participants in the treatment group of most
      clinical trials benefit equally. While subgroup analyses are often used to
      compare treatment effectiveness across pre-determined subgroups categorized by
      patient characteristics, methods to empirically identify naturally occurring
      clusters of persons who benefit most from the treatment group have rarely been
      implemented. This article provides a modeling framework to accomplish this
      important task. Utilizing information about individuals from the treatment group
      who had poor outcomes, the present study proposes an a priori clustering strategy
      that classifies the individuals with initially good outcomes in the treatment
      group into: (a) group GE (good outcome, effective), the latent subgroup of
      individuals for whom the treatment is likely to be effective and (b) group GI
      (good outcome, ineffective), the latent subgroup of individuals for whom the
      treatment is not likely to be effective. The method is illustrated through a re
      analysis of a publically available data set from the National Institute on Drug
      Abuse. The RCT examines the effectiveness of motivational enhancement therapy
      from 461 outpatients with substance abuse problems. The proposed method
      identified latent subgroups GE and GI, and the comparison between the two groups
      revealed several significantly different and informative characteristics even
      though both subgroups had good outcomes during the immediate post-therapy period.
      As a diagnostic means utilizing out-of-sample forecasting performance, the
      present study compared the relapse rates during the long-term follow-up period
      for the two subgroups. As expected, group GI, composed of individuals for whom
      the treatment was hypothesized to be ineffective, had a significantly higher
      relapse rate than group GE (63% vs. 27%; chi2 = 9.99, p-value = .002).

PMID- 25750815
TI  - Childhood-onset schizophrenia: what do we really know?
AB  - Childhood-onset schizophrenia (COS) is a rare, chronic mental illness that is
      diagnosed in children prior to the age of 13. COS is a controversial diagnosis
      among clinicians and can be very difficult to diagnose for a number of reasons.
      Schizophrenia is a psychotic disorder characterized by hallucinations, delusions,
      flat affect, limited motivation and anhedonia. The psychotic nature of this
      disorder is quite disruptive to the child's emotional regulation, behavioural
      control and can reduce the child's ability to perform daily tasks that are
      crucial to adaptive functioning. Prior to the onset of schizophrenia, children
      often develop premorbid abnormalities, which are disturbances to a child's
      functioning that may serve as warning signs. These disturbances can manifest in a
      variety of behavioural ways and may include introversion, depression, aggression,
      suicidal ideation and manic-like behaviours. This article will review the
      clinical presentation of schizophrenia in children and examine the existing
      knowledge around aetiology, treatment approaches, assessment techniques and
      differential diagnostic considerations. Gaps in the literature are identified and
      directions for future research are discussed.

PMID- 25750816
TI  - Type 2 diabetes mellitus, physical activity, exercise self-efficacy, and body
      satisfaction. An application of the transtheoretical model in older adults.
AB  - Physical activity (PA) is a relevant component of the treatment of Type 2
      diabetes mellitus (T2DM). However, to prevent its related morbidities, PA
      requires an immediate and lasting change of lifestyle. Exercise self-efficacy and
      body satisfaction were used in a sample of older adults with T2DM, classified in
      different stages of change, to predict levels of PA. Results show that exercise
      self-efficacy increases linearly from precontemplation to maintenance stage,
      while body satisfaction shows an inverted U shape. However, only stages of
      change, other than exercise self-efficacy, add a significant and noticeable
      contribution to prediction of levels of PA. This evidence claims a tailored
      approach to PA in older adults with T2DM and advises behavioural health
      interventions based on exercise self-efficacy.

PMID- 25750817
TI  - The interaction between dietary and life goals: using goal systems theory to
      explore healthy diet and life goals.
AB  - Objective: To examine the types of life and dietary goals individuals report and
      how these goal domains interact as framed by goal systems theory. Methods: This
      work is a cross-sectional survey study. Measures included the incidence of common
      life and dietary goals and how these goals interact with and facilitate each
      other. Results: The results of a quantitative survey (n = 46 participants), which
      was informed by two focus groups (n = 17 participants), showed that participants
      are trying to achieve several different life (e.g. achieving financial success)
      and dietary goals (e.g. eating more fruits and vegetables, drinking more water,
      and losing weight) and that these two types of goals interact to both facilitate
      and conflict with each other. Having a life goal of exercising was significantly
      associated with healthy eating goals when compared with other life goals (p's <
      .05), suggesting these goals may be linked and help to facilitate one another.
      Being in the maintenance phase with the goal of healthy eating was associated
      with participants feeling like they were more successful in their other non-diet
      related health goals (p < .05), suggesting maintenance of goals can facilitate
      success in achieving other goals. Conclusions: Life goals can have an impact on a
      person's ability to achieve and maintain dietary and other health goals. Health
      educators may help to facilitate long-term behavior change by examining a
      person's life goals as well as dietary goals.

PMID- 25750818
TI  - International experts' perspectives on a curriculum for psychologists working in
      primary health care: implication for Indonesia.
AB  - Enhancing primary health care to incorporate mental health services is a key
      strategy for closing the treatment gap for people with mental disorders. The
      integration of psychological care into primary health care is a critical step in
      addressing poor access to mental health specialists. As the psychology profession
      is increasingly called upon to prepare psychologists for primary health care
      settings, an international experts' consensus is valuable in guiding the
      development of a high-quality curriculum for psychologists working in the primary
      health care context. A Delphi method was used to gain a consensus on the most
      appropriate roles and training for psychologists. Initial constructs and themes
      were derived from a detailed literature review and sent to 114 international
      experts in primary mental health care from five continents. Overall, 52 experts
      who participated agreed that psychologists should have wide-ranging roles and
      skills including clinical, health promotion and advocacy skills. This study has
      identified the specific roles and training needed by psychologists to enable them
      to work more effectively in primary health care settings. The consensus will
      inform the development of a curriculum for psychologists working in primary
      health care in Indonesia, and is part of a broader suite of studies.

PMID- 25750819
TI  - Does pain mediate or moderate the relationship between physical activity and
      depressive symptoms in older people? Findings from The Irish Longitudinal Study
      on Ageing (TILDA).
AB  - Background. Depression is an increasing problem in older adults, which is
      exacerbated by under diagnosis and ineffective treatment options. Broadly
      speaking, as people age, their levels of regular physical activity (PA) decrease,
      while their experience of chronic pain increases. PA has been shown to be an
      effective, yet under-utilised, treatment for depression in this age-cohort
      although the influence of pain on the relationship between PA and depressive
      symptoms has not been considered. Methods. Secondary analysis of national data
      from The Irish Longitudinal Study on Ageing (TILDA, 2011) (n = 8163 participants
      aged 50 years and older) examined the mediating or moderating role of pain in the
      relationship between depressive symptoms and PA, and the impact of PA, pain and
      depressive symptoms on health-care utilisation. Results. Approximately 8.5% TILDA
      older adults were depressed. No mediating or moderating effects of pain were
      found in the association between PA and depressive symptoms. Higher levels of PA
      were found to be independently associated with lower depressive symptoms, while
      higher levels of pain significantly increased the likelihood of depressive
      symptoms supporting previous findings. Depressive symptoms and higher levels of
      pain were also found to significantly increase health-care utilisation.
      Conclusions. Consistent with previous findings in this field, both PA and pain
      were found to be independently associated with depressive symptoms in Irish older
      adults. Furthermore, pain does not play a mediating or moderating role in the
      relationship between PA and depressive symptoms. Continued support for ongoing
      initiatives in this area aimed at increasing PA in older adults as a means to
      improve both physical and mental well-being is advised. The absence of any
      synergistic effect between PA and pain suggests that clinicians and health
      service providers should continue to promote PA as a treatment for depression,
      irrespective of the pain levels of their patients.

PMID- 25750820
TI  - Do work relationships matter? Characteristics of workplace interactions that
      enhance or detract from employee perceptions of well-being and health behaviors.
AB  - This qualitative case study adopted the position that health and health behaviors
      are complex social constructs influenced by multiple factors. Framed by the
      social ecological model, the study explored how work interactions enhanced or
      detracted from the perceptions of well-being and health behaviors. Despite the
      fact that previous studies indicated that the social workplace environment
      contributed to employee health, there was little information regarding the
      characteristics. Specifically, little was known about how employees perceived the
      connections between workplace interactions and health, or how social interactions
      enhanced or detracted from well-being and health behaviors. The participants
      included 19 volunteers recruited from four companies, who shared their
      experiences of workplace interactions through interviews and journaling
      assignments. The findings indicated that feelings of well-being were enhanced by
      work interactions, which were trusting, collaborative, and positive, as well as
      when participants felt valued and respected. The study also found that
      interactions detracted from well-being and health behaviors when interactions
      lacked the aforementioned characteristics, and also included lack of justice and
      empathy. The enhancing and detracting relationships generated physical symptoms,
      and influenced sleeping and eating patterns, socializing, exercise, personal
      relations, careers, and energy. Surprisingly, the study found that regardless of
      how broadly participants defined health, when they were asked to rate their
      health, participants uniformly rated theirs on physical attributes alone. The
      exclusive consideration of physical attributes suggests that participants may
      have unconsciously adopted the typical western medical view of health - an
      individually determined and physiologic characteristic. Despite research
      suggesting health is more than biology, and despite defining health broadly,
      participants uniformly adopted this traditional view. The study also offers human
      resource development professionals with evidence supporting interventions aimed
      at minimizing workplace incivility. Interventions designed to improve employee
      engagement could minimize financial and human costs of negative interactions. The
      bottom line is that workplaces should be physically, emotionally, and
      psychologically safe for well-being and healthy behaviors to flourish.

PMID- 25750821
TI  - An exploratory research on the role of family in youth's drug addiction.
AB  - Most of the researches in Pakistan are concerned with the aetiological factors of
      drug addiction among the youth. However, few studies seek to explore the social
      aspects of this phenomenon. The present study aimed to explore the role of
      family, the influence of parental involvement, and communication styles in
      youth's drug addiction in a qualitative manner. Twenty drug addicts (age range 18
      28 years) were taken as a sample from drug rehabilitation centres in Rawalpindi
      and Islamabad, Pakistan. A structured interview guide was administered comprising
      questions related to the individual's habits, relationship with family and
      friends, and modes of communication within the family. Case profiles of the
      participants were also taken. The rehabilitation centres offered family therapy
      and the researcher, as a non-participant, observed these sessions as part of the
      analysis. The demographic information revealed that majority of the participants
      were poly-substance abusers (80%) and the significant reasons for starting drugs
      were the company of peers and curiosity. The thematic analysis revealed parental
      involvement and emotional expressiveness as two major components in family
      communication. It was found that parents were concerned about their children, but
      were not assertive in the implementation of family rules. It was also found that
      the major life decisions of the participants were taken by their parents, which
      is a characteristic of collectivist Pakistani society.

PMID- 25750822
TI  - Health anxiety and healthcare costs in Japanese individuals: an Internet survey.
AB  - Aim: Health anxiety, also known as hypochondriasis, is classifiable as an anxiety
      disorder. The aim of this study was to examine the relationship between health
      anxiety and healthcare costs. Method: Participants - 100 Japanese individuals
      from the general population with chronic health problems and 100 without chronic
      health problems - were recruited via the Internet. They completed self-report
      scales measuring health anxiety, state anxiety, depression, obsessionality, and a
      scale specifically developed for this study that measured the use of healthcare
      services and the personal costs of respondents' healthcare. Results: Health
      anxiety was associated with more incidents of inpatient care and greater
      healthcare expenditure. These associations remained significant even after
      controlling for state anxiety, depression, obsessionality, and the presence of
      chronic health problems. Conclusion: We conclude that health anxiety is related
      to personal as well as social costs in Japan.

PMID- 25750825
TI  - The impact of chronic illness in suicidality: a qualitative exploration.
AB  - Objectives: To explore the experiences of patients with chronic physical illness
      in relation to suicidal behaviours and ideas. Design: A qualitative study using
      semi-structured interviews. Methods: Fourteen patients with either multiple
      sclerosis or stage 5 chronic kidney disease were interviewed. Grounded theory was
      used to analyse the data. Results: Suicidal ideation was commonly reported by the
      study participants, and the relationship between the impact of a chronic physical
      illness, suicidality and risk factors was described. Several participants
      reported having planned suicide attempts as a consequence of finding living with
      their illness intolerable, and some had used non-adherence to treatment as a
      deliberate method to end their life. Conclusion: The findings suggest suicidality
      may be a relatively common experience in those with chronic illness facing a
      future of further losses, and that alongside passive thoughts of not being alive
      this may also include active thoughts about suicide. Health professionals should
      be alert to intentional non-adherence to treatment as an attempt to end one's
      life.

PMID- 25750824
TI  - Posttraumatic stress in intensive care unit survivors - a prospective study.
AB  - Aims: This study aimed to estimate the prevalence of severe Posttraumatic Stress
      Disorder (PTSD) symptoms and to identify factors associated with PTSD in
      survivors of intensive care unit (ICU) treatment following traumatic injury.
      Methods: Fifty-two patients who were admitted to an ICU through the emergency
      ward following traumatic injury were prospectively followed. Information on
      injury severity and ICU treatment were obtained through medical records.
      Demographic information and measures of acute stress symptoms, experienced social
      support, coping style, sense of coherence (SOC) and locus of control were
      assessed within one-month post-accident (T1). At the six months follow-up (T2),
      PTSD was assessed with the Harvard Trauma Questionnaire (HTQ). Results: In the
      six months follow-up, 10 respondents (19.2%) had HTQ total scores reaching a
      level suggestive of PTSD (N = 52), and 11 respondents (21%) had symptom levels
      indicating subclinical PTSD. Female, five illness factors: coma time, mechanical
      ventilation, sedation, benzodiazepine, pain relieving medication, and four
      psychological factors: symptoms of acute stress (T1), fear of death and/or
      feeling completely helpless and powerless in relation to the accident and/or ICU
      (T1), SOC (T1) and more external locus of control (T1) correlated significantly
      with PTSD symptoms at T2. In the linear regression analysis, female, length of
      sedation, dissociation (T1), hypervigilance (T1), and external locus of control
      predicted 58% of the variation of PTSD. Conclusions: High levels of PTSD symptoms
      occurred in 19.2% of respondents in six months following traumatic injury
      requiring ICU admission. Screening for the variables gender, length of sedation,
      dissociation, hypervigilance, and locus of control after ICU admission following
      traumatic injuries may help to predict who will develop PTSD.

PMID- 25750823
TI  - Online interventions for depression and anxiety - a systematic review.
AB  - Background: Access to mental health care is limited. Internet-based interventions
      (IBIs) may help bridge that gap by improving access especially for those who are
      unable to receive expert care. Aim: This review explores current research on the
      effectiveness of IBIs for depression and anxiety. Results: For depression,
      therapist-guided cognitive behavioral therapy (CBT) had larger effect sizes
      consistently across studies, ranging from 0.6 to 1.9; while stand-alone CBT
      (without therapist guidance) had a more modest effect size of 0.3-0.7. Even other
      interventions for depression (non-CBT/non-randomized controlled trial (RCT))
      showed modestly high effect sizes (0.2-1.7). For anxiety disorders, studies
      showed robust effect sizes for therapist-assisted interventions with effect sizes
      of 0.7-1.7 (efficacy similar to face-to-face CBT) and stand-alone CBT studies
      also showed large effect sizes (0.6-1.7). Non-CBT/Non-RCT studies (only 3) also
      showed significant reduction in anxiety scores at the end of the interventions.
      Conclusion: IBIs for anxiety and depression appear to be effective in reducing
      symptomatology for both depression and anxiety, which were enhanced by the
      guidance of a therapist. Further research is needed to identify various
      predictive factors and the extent to which stand-alone Internet therapies may be
      effective in the future as well as effects for different patient populations.

PMID- 25750826
TI  - Diet behaviour among young people in transition to adulthood (18-25 year olds): a
      mixed method study.
AB  - Background: Young people (18-25 years) during the adolescence/adulthood
      transition are vulnerable to weight gain and notoriously hard to reach. Despite
      increased levels of overweight/obesity in this age group, diet behaviour, a major
      contributor to obesity, is poorly understood. The purpose of this study was to
      explore diet behaviour among 18-25 year olds with influential factors including
      attitudes, motivators and barriers. Methods: An explanatory mixed method study
      design, based on health Behaviour Change Theories was used. Those at
      University/college and in the community, including those Not in Education,
      Employment or Training (NEET) were included. An initial quantitative
      questionnaire survey underpinned by the Theory of Planned Behaviour and Social
      Cognitive Theory was conducted and the results from this were incorporated into
      the qualitative phase. Seven focus groups were conducted among similar young
      people, varying in education and socioeconomic status. Exploratory univariate
      analysis was followed by multi-staged modelling to analyse the quantitative data.
      'Framework Analysis' was used to analyse the focus groups. Results: 1313
      questionnaires were analysed. Self-reported overweight/obesity prevalence was
      22%, increasing with age, particularly in males. Based on the survey, 40% of
      young people reported eating an adequate amount of fruits and vegetables and 59%
      eating regular meals, but 32% reported unhealthy snacking. Based on the
      statistical modelling, positive attitudes towards diet and high intention (89%),
      did not translate into healthy diet behaviour. From the focus group discussions,
      the main motivators for diet behaviour were 'self-appearance' and having 'variety
      of food'. There were mixed opinions on 'cost' of food and 'taste'. Conclusion:
      Elements deemed really important to young people have been identified. This mixed
      method study is the largest in this vulnerable and neglected group covering a
      wide spectrum of the community. It provides evidence base to inform tailored
      interventions for a healthy diet within this age group.

PMID- 25750827
TI  - Unique and shared techniques in cognitive-behavioural and short-term
      psychodynamic psychotherapy: a content analysis of randomised trials on
      depression.
AB  - Randomised controlled trials (RCTs) of psychotherapeutic interventions assume
      that specific techniques are used in treatments, which are responsible for
      changes in the client's symptoms. This assumption also holds true for meta
      analyses, where evidence for specific interventions and techniques is compiled.
      However, it has also been argued that different treatments share important
      techniques and that an upcoming consensus about useful treatment strategies is
      leading to a greater integration of treatments. This makes assumptions about the
      effectiveness of specific interventions ingredients questionable if the shared
      (common) techniques are more often used in interventions than are the unique
      techniques. This study investigated the unique or shared techniques in RCTs of
      cognitive-behavioural therapy (CBT) and short-term psychodynamic psychotherapy
      (STPP). Psychotherapeutic techniques were coded from 42 masked treatment
      descriptions of RCTs in the field of depression (1979-2010). CBT techniques were
      often used in studies identified as either CBT or STPP. However, STPP techniques
      were only used in STPP-identified studies. Empirical clustering of treatment
      descriptions did not confirm the original distinction of CBT versus STPP, but
      instead showed substantial heterogeneity within both approaches. Extraction of
      psychotherapeutic techniques from the treatment descriptions is feasible and
      could be used as a content-based approach to classify treatments in systematic
      reviews and meta-analyses.

PMID- 25750828
TI  - The support needs of terminally ill people living alone at home: a narrative
      review.
AB  - Context: The number of terminally ill people who live alone at home and without a
      caregiver is growing and exerting pressure on the stretched resources of home
      based palliative care services. Objectives: We aimed to highlight the unmet
      support needs of terminally ill people who live alone at home and have no primary
      caregiver and identify specific models of care that have been used to address
      these gaps. Methods: We conducted a narrative review of empirical research
      published in peer-reviewed journals in English using a systematic approach,
      searching databases 2002-2013. This review identified 547 abstracts as being
      potentially relevant. Of these, 95 were retrieved and assessed, with 37 studies
      finally reviewed. Results: Majority of the studies highlighted the reduced
      likelihood of this group to be cared for and die at home and the experiences of
      more psychosocial distress and more hospital admissions than people with a
      primary caregiver. Few studies reported on the development of models of care but
      showed that the challenges faced by this group may be mitigated by interventions
      tailored to meet their specific needs. Conclusion: This is the first review to
      highlight the growing challenges facing community palliative care services in
      supporting the increasing number of people living alone who require care. There
      is a need for more studies to examine the effectiveness of informal support
      networks and suitable models of care and to provide directions that will inform
      service planning for this growing and challenging group.

PMID- 25750829
TI  - Australian experts' perspectives on a curriculum for psychologists working in
      primary health care: implication for Indonesia.
AB  - In Indonesia there is a pressing need to scale up mental health services due to a
      substantial unmet need for mental health care. Integrating psychologists into
      primary health care can potentially deliver affordable mental health services to
      communities and help to close the treatment gap. Australia is one of the pioneers
      in integrating mental health into primary health care, and the mental health
      reforms in Australia may have some implications for Indonesia. The aim of this
      paper is to examine the Australian experience and to reflect in particular on
      lessons that may be learnt to inform the development of curriculum for
      psychologists working in primary health care in Indonesia. Data were collected
      through semi-structured interviews with 12 Australian experts in primary mental
      health care. The focus of the interview was on the roles and skills of
      psychologists working in primary health care with a particular focus on the
      appropriate curriculum for psychologists. Overall, the Australian experts agreed
      that psychologists' roles and training should include both clinical skills and
      public mental health skills. The experts also agreed that psychologists should be
      able to educate the community about mental health issues and be capable of
      undertaking research and evaluation of programs. A central theme was the need for
      strong collaborations with general practitioners and existing agencies in the
      community so that psychologists are able to make appropriate referrals and also
      accept referrals. The lessons learnt from the Australian experience, which are
      most applicable to the Indonesian setting are: (1) the importance of adequate
      government funding of psychologists; (2) the value of evidence-based treatments
      such as Cognitive Behavioural Therapy; (3) the need to specifically train
      psychologists for primary care; (4) the need for flexibility in the psychologist
      workforce (e.g. location); and (5) the value of continuing supervision for
      psychologists to support them in their role.

PMID- 25750830
TI  - Workplace risk factors for anxiety and depression in male-dominated industries: a
      systematic review.
AB  - Background and Aims: Working conditions are an important health determinant.
      Employment factors can negatively affect mental health (MH), but there is little
      research on MH risk factors in male-dominated industries (MDI). Method: A
      systematic review of risk factors for anxiety and depression disorders in MDI was
      undertaken. MDI comprised >= 70% male workers and included agriculture,
      construction, mining, manufacturing, transport and utilities. Major electronic
      databases (CINAHL, Cochrane Library, Informit, PsycINFO, PubMed and Scopus) were
      searched. Each study was categorised according to National Health and Medical
      Research Council's hierarchy of evidence and study quality was assessed according
      to six methodological criteria. Results: Nineteen studies met the inclusion
      criteria. Four categories of risk were identified: individual factors, team
      environment, work conditions and work-home interference. The main risk factors
      associated with anxiety and depression in MDI were poor health and lifestyles,
      unsupportive workplace relationships, job overload and job demands. Some studies
      indicated a higher risk of anxiety and depression for blue-collar workers.
      Conclusion: Substantial gaps exist in the evidence. Studies with stronger
      methodologies are required. Available evidence suggests that comprehensive
      primary, secondary and tertiary prevention approaches to address MH risk factors
      in MDI are necessary. There is a need for organisationally focused workplace MH
      policies and interventions.

PMID- 25750831
TI  - Students' benefits and barriers to mental health help-seeking.
AB  - Stigma is recognized as a potential barrier to seeking help for a mental health
      disorder. The present study assessed college students' perceived benefits and
      barriers to obtaining mental health treatment and stigma-related attitudes via a
      four-page survey. A total of 682 students at one Midwestern university
      participated in the study. Findings indicated that females perceived a greater
      number of benefits to having participated in mental health services and held
      significantly lower stigma-related attitudes than did males. Students who had
      ever received mental health services reported significantly more barriers to
      treatment than did students who had never received services. Health professionals
      should target students with educational programs about positive outcomes related
      to receiving mental health services and work with treatment centers to reduce
      barriers for receiving services.

PMID- 25750832
TI  - Low perceived social support predicts later depression but not social phobia in
      middle adolescence.
AB  - Social phobia and depression are common and highly comorbid disorders in
      adolescence. There is a lack of studies on possible psychosocial shared risk
      factors for these disorders. The current study examined if low social support is
      a shared risk factor for both disorders among adolescent girls and boys. This
      study is a part of the Adolescent Mental Health Cohort Study's two-year follow
      up. We studied cross-sectional and longitudinal associations of perceived social
      support with social phobia, depression, and comorbid social phobia and depression
      among girls and boys. The study sample consisted of 2070 15-year-old adolescents
      at baseline. Depression was measured by the 13-item Beck Depression Inventory,
      social phobia by the Social Phobia Inventory (SPIN), and perceived social support
      by the Perceived Social Support Scale-Revised (PSSS-R). Girls reported higher
      scores on the PSSS-R than boys in total scores and in friend and significant
      other subscales. Cross-sectional PSSS-R scores were lower among adolescents with
      social phobia, depression, and comorbid disorder than among those without these
      disorders. Low PSSS-R total score and significant other subscale were risk
      factors for depression among both genders, and low support from friends among
      girls only. Low perceived social support from any source was not a risk factor
      for social phobia or comorbid social phobia and depression. As conclusion of the
      study, low perceived social support was a risk factor for depression, but not a
      shared risk factor for depression and social phobia. Interventions enhancing
      perceived social support should be an important issue in treatment of depression.

PMID- 25750833
TI  - Recalled attributes of parents with Alzheimer's disease: relevance for
      caregiving.
AB  - Health psychology has long been involved in studies of factors that lead to more
      effective caregiving. Drawing on the theory of distributive justice, the
      underlying hypothesis of this paper was that perceptions of what a demented
      parent was like, prior to becoming ill, influence an adult child caregiver's
      provision of care, as well as the caregiver's own well-being. A secondary
      question dealt with the nature of retrospective ratings by caregiver informants.
      The sample consisted of triads of two adult children (N = 385) and a parent (N =
      201) diagnosed with Alzheimer's disease, although in a few instances only one
      adult child was interviewed. Both retrospective and current ratings of the parent
      were made by caregivers, who were administered a semantic differential instrument
      twice over a 10-month period. Comparison of ratings from first and second
      interview waves suggested that perceptions of what a parent was like, prior to
      the onset of dementia, were more stable over time than perceptions of what the
      parent was currently like, at each interview. Ratings of premorbid attributes
      were more strongly related to ratings of the present for those parents who
      displayed the least evidence of cognitive decline. Regression analyses supported
      the hypothesized relationship between adult children's perceptions and both
      provision of care and well-being variables. Results have implications for
      projections of caregiver burden and for placement into long-term care.

PMID- 25750834
TI  - Changes in language use mediate expressive writing's benefits on health-related
      quality of life following myocardial infarction.
AB  - The present study assessed linguistic mediators on the effects of expressive
      writing on health-related quality of life (HRQOL), depression and anxiety
      following myocardial infarction (MI). One hundred and twenty-one cardiac patients
      were randomised (expressive writing = 61; control = 60), 98 (expressive writing =
      47; control = 51) provided pre- and post-data, with 89 (expressive writing = 43;
      control = 46) completing the three-month follow-up. The expressive writing group
      wrote (20 mins/day for three consecutive days) about their thoughts and feelings
      regarding their MI, and the control group wrote (20 mins/day for three
      consecutive days) about daily events that occurred during the year prior to the
      MI. The outcome measures of depression, anxiety and HRQOL were completed pre
      randomisation, post-intervention and three months post-intervention; the
      mediating variables assessed were changes in (a) positive emotion words, (b)
      negative emotion words and (c) cognitive-processing words. Three months post
      intervention, the expressive writing group had significantly higher HRQOL. The
      positive effects of expressive writing were significantly associated with
      increases in both positive emotion words and cognitive-processing words across
      the three days of expressive writing. Expressive writing is a beneficial
      intervention that may enhance HRQOL among cardiac patients.

PMID- 25750835
TI  - Maladaptive rumination moderates the effects of written emotional disclosure on
      ambulatory blood pressure levels in females.
AB  - Written emotional disclosure (WED) has beneficial effects on health outcomes.
      However, its effectiveness is influenced by a number of variables. This
      exploratory study tested whether trait rumination, which comprises brooding, a
      maladaptive component, and reflection, an adaptive component, moderated the
      effects of WED on ambulatory blood pressure (ABP) in female participants. Fifty
      two participants were randomized to write about their most stressful/traumatic
      life experience(s) or non-emotive topics, for 20 minutes, on 3 consecutive days.
      Two weeks and 14 weeks later, ABP was recorded over a single day. Using
      hierarchical linear modelling, an effect of condition was found at 2 weeks but
      not at 14 weeks indicating that higher levels of ABP were observed following WED.
      There was also a significant condition by brooding interaction at two weeks such
      that higher ABP was observed in low brooders in the WED condition compared with
      low brooders in the control condition. However, within the WED condition, the
      lowest ABP was exhibited by participants high in brooding. The findings indicated
      that WED led to short-lived increases in ABP which disappeared in the medium
      term. Researchers ought to build upon this exploratory study and investigate
      further the potential moderating role of brooding within WED. Individual
      differences in brooding may account for (some of) the mixed and inconsistent
      findings in past WED research.

PMID- 25750836
TI  - Contributions of Feature Binding During Encoding and Functional Connectivity of
      the Medial Temporal Lobe Structures to Episodic Memory Deficits Across the
      Prodromal and First-Episode Phases of Schizophrenia.
AB  - Patients with and at risk for psychosis may have difficulty using associative
      strategies to facilitate episodic memory encoding and recall. In parallel
      studies, patients with first-episode schizophrenia (n = 27) and high psychosis
      risk (n = 28) compared with control participants (n = 22 and n = 20,
      respectively) underwent functional MRI during a remember-know memory task.
      Psychophysiological interaction analyses, using medial temporal lobe (MTL)
      structures as regions of interest, were conducted to measure functional
      connectivity patterns supporting successful episodic memory. During encoding,
      patients with first-episode schizophrenia demonstrated reduced functional
      coupling between MTL regions and regions involved in stimulus representations,
      stimulus selection, and cognitive control. Relative to control participants and
      patients with high psychosis risk who did not convert to psychosis, patients with
      high psychosis risk who later converted to psychosis also demonstrated reduced
      connectivity between MTL regions and auditory-verbal and visual-association
      regions. These results suggest that episodic memory deficits in schizophrenia are
      related to inefficient recruitment of cortical connections involved in
      associative memory formation; such deficits precede the onset of psychosis among
      those individuals at high clinical risk.

PMID- 25750837
TI  - ICD-11 Complex PTSD in US National and Veteran Samples: Prevalence and Structural
      Associations with PTSD.
AB  - The eleventh edition of the International Classification of Diseases (ICD-11) is
      under development and current proposals include major changes to trauma-related
      psychiatric diagnoses, including a heavily restricted definition of posttraumatic
      stress disorder (PTSD) and the addition of complex PTSD (CPTSD). We aimed to test
      the postulates of CPTSD in samples of 2695 community participants and 323 trauma
      exposed military veterans. CPTSD prevalence estimates were 0.6% and 13% in the
      community and veteran samples, respectively; one-quarter to one-half of those
      with PTSD met criteria for CPTSD. There were no differences in trauma exposure
      across diagnoses. A factor mixture model with two latent dimensional variables
      and four latent classes provided the best fit in both samples: classes differed
      by their level of symptom severity but did not differ as a function of the
      proposed PTSD versus CPTSD diagnoses. These findings should raise concerns about
      the distinctions between CPTSD and PTSD proposed for ICD-11.

PMID- 25750838
TI  - Spiritual and Religious Resources in African American Women: Protection from
      Depressive Symptoms Following Birth.
AB  - Many women experience depressive symptoms after birth, and rates among African
      Americans are as high as 40 percent. Spirituality and religiosity are valued in
      African American communities, but their relevance to new mothers has not been
      empirically tested. We examined effects of religiosity and spirituality on
      trajectories of depressive symptoms during the year following childbirth. Data
      were collected by the Eunice Kennedy Shriver NICHD Community and Child Health
      Network (CCHN) focused on maternal-child health disparities. The sample consisted
      of 702 low SES African American predominantly Christian women. Participants were
      interviewed in their homes throughout the year following a birth. Spirituality
      and religiosity each independently predicted changes in depressive symptoms with
      low levels predicting increases over time. Effects of religiosity were mediated
      by a woman's spirituality. Religiosity and spirituality functioned as
      significant, interrelated protective factors in this study which provides novel
      insight about lower income African American women following birth.

PMID- 25750839
TI  - Preservation of frontal sinus anatomy and outflow tract following frontal trauma
      with dural defect.
AB  - Our case report describes a young male mechanic who was hit in his face by a
      spring while repairing a car, resulting in traumatic injury to the frontal sinus,
      with fractures of both the anterior and the posterior tables with dural defect
      and cerebrospinal fluid leak. Current guidelines recommend that comminuted and/or
      displaced fractures of the posterior table of the frontal sinus with dural
      defects should be either cranialized or obliterated. In this patient, instead of
      cranializing or obliterating the frontal sinus, we managed to preserve the
      frontal sinus anatomy and its outflow tract using a combined open bicoronal and
      nasoendoscopic approach. This avoids the long-term complications associated with
      cranialization or obliteration including mucocele formation and frontocutaneous
      fistula. 

PMID- 25750840
TI  - An assessment of histological margins and recurrence of melanoma in situ.
AB  - BACKGROUND: Melanoma in situ (MIS) accounts for up to 27% of all melanomas. MIS
      has no metastatic potential and the aim should be to excise the lesion completely
      with a clear histological margin, although margin clearance remains undefined. We
      aimed to assess the relation of histological excision margins of MIS to
      recurrence and progression to invasive disease. METHODS: We analyzed all patients
      with MIS excised by wide local excision or staged excision in our institution
      over a 5-year period from December 2008 to January 2014 using a prospectively
      maintained database. Clinicopathologic details included patient demographics,
      anatomical site of lesion, melanoma subtype, histological excision margin, and
      recurrence. RESULTS: A total of 410 patients had MIS excised during this time,
      the majority of which were lentigo maligna subtype (79%). The average
      histological excision margin was 3.7 mm. The rate of recurrence was 2.2% (9/410),
      with a median follow-up of 23 months. Lentigo maligna had a similar rate of
      recurrence to non-lentigo MIS (2.3% vs 1.2%) (P = 0.69). The mean excision margin
      of those that recurred was 1.9 mm compared with an average of 3.8 mm in those
      that did not. The rate of recurrence of MIS with histological excision margin
      <=3.00 mm was 3.8% compared with 0.5% in those with a histological margin >3.00
      mm (P = 0.03). One case of MIS recurred as invasive disease. CONCLUSION: At
      institutions using wide local excision or staged excision for MIS, a histological
      margin of >3.0 mm is required to achieve a low recurrence rate.

PMID- 25750842
TI  - The lipogluteoplasty in circumferential bodylifting.

PMID- 25750841
TI  - Combined Submental-tongue Flap for Reconstruction of Subtotal Traumatic Avulsion
      of Lower Lip: A Technical Note.
AB  - Delayed reconstruction of large lower lip defects after traumatic avulsion is a
      challenge in medically compromised patients with concomitant cheek skin burn.
      Combination of orthograde submental transposition flap and anteriorly based
      ventral rectangular myomucosal tongue flap is useful. The former reconstructs the
      body of the defect, and the latter masks the red lip, resembling vermilion. In
      this article, the detailed surgical technique is explained. Literature review of
      tongue flap and submental flap in the lower lip reconstruction is presented. 

PMID- 25750843
TI  - Obstruction of vena cava and collateral flow after abdominal reconstruction for
      gastroschisis.
AB  - The upper limit of intra-abdominal pressure after closure of gastroschisis has
      been suggested around 20 mm Hg. An acute abdominal compartmental syndrome may
      produce intestinal ischemia with perforation and hepatic or renal failure. We
      present a case of a baby born with gastroschisis and ileal atresias 2 decades
      ago. The closure of the defect entailed a borderline abdominal compartmental
      syndrome with caval occlusion and development of collateral venous circulation.
      This was evidenced by a phlebographic study at the age of 8. At the age of 19,
      the patient continued to show a superficial, varicose net and some aesthetic
      concerns. This minor condition seems not previously reported. The authors intend
      to raise awareness about current methods for indirect assessment of intra
      abdominal pressure when performing abdominal reconstruction for a gastroschisis
      defect. 

PMID- 25750844
TI  - Mandibular metastases of papillary thyroid carcinoma treated by
      hemimandibulectomy and costochondral rib graft.
AB  - Papillary thyroid carcinoma (PTC) is the most common and well-differentiated
      cancer of the thyroid. Unlike most cancers, spread to local lymph node does not
      worsen the survival rate of PTC, and complete resection of the metastases seems
      to be important and may have favorable effects on the prognosis. A 33-year-old
      woman was referred to our clinic with a mass involving the right angulus
      mandible. Incisional biopsy of the mass diagnosed follicular variant of papillary
      thyroid carcinoma. Right hemimandibulectomy was performed and reconstructed with
      costochondral rib graft. The patient survived for 5 years after the
      hemimandibulectomy. Metastases to the oral cavity indicate a grave prognosis, but
      PTC has relatively indolent biological behavior; long-term survival is usually
      possible even in patients with metastatic disease. 

PMID- 25750845
TI  - Closure of huge palatal fistula in an adult patient with isolated cleft palate: a
      technical note.
AB  - Closure of huge palatal fistula surrounded by fully erupted permanent dentition
      in the adult patients with cleft is a challenge. Posteriorly based buccinator
      myomucosal flap is a neurovascular pedicled flap, with inherent nature of thin
      thickness, saliva secretion, and axial pattern blood supply. Vicinity of donor
      site to the palate and low donor-site morbidity are the other advantages. It is
      an ideal choice in such situation. In this article, the details of surgical
      technique and the effectiveness of this method are presented. 

PMID- 25750846
TI  - Current Status of Surgical Planning for Orthognathic Surgery: Traditional Methods
      versus 3D Surgical Planning.
AB  - BACKGROUND: Orthognathic surgery has traditionally been performed using stone
      model surgery. This involves translating desired clinical movements of the
      maxilla and mandible into stone models that are then cut and repositioned into
      class I occlusion from which a splint is generated. Model surgery is an accurate
      and reproducible method of surgical correction of the dentofacial skeleton in
      cleft and noncleft patients, albeit considerably time-consuming. With the advent
      of computed tomography scanning, 3D imaging and virtual surgical planning (VSP)
      have gained a foothold in orthognathic surgery with VSP rapidly replacing
      traditional model surgery in many parts of the country and the world. What has
      yet to be determined is whether the application and feasibility of virtual model
      surgery is at a point where it will eliminate the need for traditional model
      surgery in both the private and academic setting. METHODS: Traditional model
      surgery was compared with VSP splint fabrication to determine the feasibility of
      use and accuracy of application in orthognathic surgery within our institution.
      RESULTS: VSP was found to generate acrylic splints of equal quality to model
      surgery splints in a fraction of the time. Drawbacks of VSP splint fabrication
      are the increased cost of production and certain limitations as it relates to
      complex craniofacial patients. CONCLUSIONS: It is our opinion that virtual model
      surgery will displace and replace traditional model surgery as it will become
      cost and time effective in both the private and academic setting for
      practitioners providing orthognathic surgical care in cleft and noncleft
      patients.

PMID- 25750847
TI  - Total nasal skeletal reconstruction disfigured by granulomatosis with polyangitis
      (wegener granulomatosis).
AB  - BACKGROUND: Nasal deformity is a common disorder in Wegener granulomatosis, which
      is produced by polyangitis of medium-sized vessels. This process may cause
      necrosis and destruction of the nasal mucosa and osteocartilaginous framework. At
      this time, there is a lack of published data on nasal deformities associated with
      Wegener granulomatosis. METHODS: We present a 53-year-old woman with completely
      necrotized nasal lining and osteocartilage. The patient had a history of
      granulomatosis with polyangitis that was currently in remission. We reconstructed
      the patient's nose with fifth and sixth rib cartilages over 3 successive
      surgeries over a 2-year period. RESULTS: During the 3-year follow-up period,
      neither infection nor significant cartilage graft resorption was observed, and
      the aesthetic result was acceptable both to the patient and her physicians.
      CONCLUSIONS: In spite of contamination to the nasal lining and immune
      compromising medications, nasal reconstruction is usually successful when
      considering these factors. Access to strong and abundant fifth or sixth rib
      cartilage presents an opportunity to reconstruct nasal destruction due to
      iatrogenic or autoimmune processes.

PMID- 25750848
TI  - Establishing a Reproducible Hypertrophic Scar following Thermal Injury: A Porcine
      Model.
AB  - BACKGROUND: Our complete understanding of hypertrophic scarring is still
      deficient, as portrayed by the poor clinical outcomes when treating them. To
      address the need for alternative treatment strategies, we assess the swine animal
      burn model as an initial approach for immature scar evaluation and therapeutic
      application. METHODS: Thermal contact burns were created on the dorsum of 3
      domestic swine with the use of a branding iron at 170 degrees F for 20 seconds.
      Deep partial-thickness burns were cared for with absorptive dressings over 10
      weeks and wounds evaluated with laser and negative pressure transduction,
      histology, photographic analysis, and RNA isolation. RESULTS: Overall average
      stiffness (mm Hg/mm) increased and elasticity (mm) decreased in the scars from
      the initial burn injury to 8 weeks when compared with normal skin (P < 0.01).
      Scars were thicker, more erythematous, and uniform in the caudal dorsum. The
      percent change of erythema in wounds increased from weeks 6 to 10. Histology
      demonstrated loss of dermal papillae, increased myofibroblast presence,
      vertically oriented vessels, epidermal and dermal hypercellularity, and parallel
      layered collagen deposition. Immature scars remained elevated at 10 weeks, and
      minimal RNA was able to be isolated from the tissue. CONCLUSIONS: Deep partial
      thickness thermal injury to the back of domestic swine produces an immature
      hypertrophic scar by 10 weeks following burn with thickness appearing to coincide
      with the location along the dorsal axis. With minimal pig to pig variation, we
      describe our technique to provide a testable immature scar model.

PMID- 25750849
TI  - Intraoperative Use of Indocyanine Green Fluorescence Angiography during Distally
      Based Radial Artery Perforator Flap for Squamous Cell Carcinoma of the Thumb.
AB  - Distally based radial artery perforator flap (DBRAPF) is useful for hand defects;
      however, the location of the perforator varies among individuals. Preoperative
      evaluation has been a problematic issue when performing this flap. A 64-year-old
      man developed squamous cell carcinoma on an old burn scar at the dorsal thumb and
      was referred to our clinic for further treatment. After wide resection of the
      tumor, including the long and short extensors of the thumb, we reconstructed the
      defect with DBRAPF. At that time, near-infrared fluorescence angiography with
      indocyanine green (ICG) was used to identify the position of the perforator.
      After injecting ICG intravenously, we could observe its uptake at approximately 5
      cm proximal to the styloid process. We designed a 10 * 6 cm island flap with that
      uptake as pivot point. During flap elevation, the perforator could be confirmed
      at the point of uptake; the flap was then transferred to the defect by rotating
      the pedicle at the identified point. The vascularity of the flap could also be
      checked intraoperatively through ICG angiography. The tip of the flap that showed
      weak ICG fluorescence indicated epidermal necrosis. Nevertheless, the entire flap
      was viable and enabled good functionality without tumor recurrence and metastasis
      after 5 years. Using ICG angiography, DBRAPF could be performed smoothly, easily,
      and safely. 

PMID- 25750850
TI  - A novel nonsurgical treatment for pincer nail that involves mechanical force
      control.
AB  - We hypothesize that nails have an automatic curvature feature and that their flat
      shape is maintained by the daily upward mechanical forces from the finger/toe
      pad. Thus, nail deformities, such as pincer nail, spoon nail, and koilonychias,
      may be caused by an imbalance between these forces and can be treated by
      controlling these forces. Here, we report the case of a 55-year-old man whose
      severe pincer nail was effectively treated by thinning the nail, which reduced
      the automatic curvature force. This is the first report to show that pincer nail
      can be treated by a nonsurgical method that reduces the automatic curvature
      force, thus obviating the need for surgery. This supports the notion that
      mechanical stimulus-based treatments have high therapeutic potential for nail
      deformities. 

PMID- 25750851
TI  - Video Capture of Plastic Surgery Procedures Using the GoPro HERO 3+.
AB  - BACKGROUND: Significant improvements can be made in recoding surgical procedures,
      particularly in capturing high-quality video recordings from the surgeons' point
      of view. This study examined the utility of the GoPro HERO 3+ Black Edition
      camera for high-definition, point-of-view recordings of plastic and
      reconstructive surgery. METHODS: The GoPro HERO 3+ Black Edition camera was head
      mounted on the surgeon and oriented to the surgeon's perspective using the GoPro
      App. The camera was used to record 4 cases: 2 fat graft procedures and 2 breast
      reconstructions. During cases 1-3, an assistant remotely controlled the GoPro via
      the GoPro App. For case 4 the GoPro was linked to a WiFi remote, and controlled
      by the surgeon. RESULTS: Camera settings for case 1 were as follows: 1080p video
      resolution; 48 fps; Protune mode on; wide field of view; 16:9 aspect ratio. The
      lighting contrast due to the overhead lights resulted in limited washout of the
      video image. Camera settings were adjusted for cases 2-4 to a narrow field of
      view, which enabled the camera's automatic white balance to better compensate for
      bright lights focused on the surgical field. Cases 2-4 captured video sufficient
      for teaching or presentation purposes. CONCLUSIONS: The GoPro HERO 3+ Black
      Edition camera enables high-quality, cost-effective video recording of plastic
      and reconstructive surgery procedures. When set to a narrow field of view and
      automatic white balance, the camera is able to sufficiently compensate for the
      contrasting light environment of the operating room and capture high-resolution,
      detailed video.

PMID- 25750852
TI  - Culture, inequality, and health: evidence from the MIDUS and MIDJA comparison.
AB  - This article seeks to forge scientific connections between three overarching
      themes (culture, inequality, health). Although the influence of cultural context
      on human experience has gained notable research prominence, it has rarely
      embraced another large arena of science focused on the influence social
      hierarchies have on how well and how long people live. That literature is
      increasingly focused psychosocial factors, working interactively with biological
      and brain-based mechanisms, to account for why those with low socioeconomic
      standing have poorer health. Our central question is whether and how these
      processes might vary by cultural context. We draw on emerging findings from two
      parallel studies, Midlife in the U.S. and Midlife in Japan, to illustrate the
      cultural specificity evident in how psychosocial and neurobiological factors are
      linked with each other as well as how position in social hierarchies matters for
      psychological experience and biology. We conclude with suggestions for future
      multidisciplinary research seeking to understand how social hierarchies matter
      for people's health, albeit in ways that may possibly differ across cultural
      contexts.

PMID- 25750854
TI  - Invasive rhino-orbito-cerebral mucormycosis in a diabetic patient - the need for
      prompt treatment.
AB  - Mucormycosis is a rare life threatening fungal infection predominately seen in
      immunocompromised or diabetic patients. The following case is of a known type II
      diabetic patient who presented with sepsis and sudden unilateral loss of vision
      secondary to infective rhino-orbito-cerebral mucormycosis. Treatment of the
      condition required extensive surgical intervention and medical management for a
      life saving outcome. 

PMID- 25750853
TI  - The Effects of Aerobic Exercise on Cognitive and Neural Decline in Aging and
      Cardiovascular Disease.
AB  - Aging is characterized by a decline in cognitive functions, particularly in the
      domains of executive function, processing speed and episodic memory. These age
      related declines are exacerbated by cardiovascular disease (CVD) and
      cardiovascular risk factors (hypertension, diabetes, obesity, elevated total
      cholesterol). Structural and functional alterations in brain regions, including
      the fronto-parietal and medial temporal lobes, have been linked to age- and CVD
      related cognitive decline. Multiple recent studies indicate that aerobic exercise
      programs may slow the progression of age-related neural changes and reduce the
      risk for mild cognitive impairment as well as dementia. We review age- and CVD
      related decline in cognition and the underlying changes in brain morphology and
      function, and then clarify the impact of aerobic exercise on moderating these
      patterns.

PMID- 25750855
TI  - Cutaneous infection by different Alternaria species in a liver transplant
      recipient.
AB  - Fungal invasive infections are rare in general population but are an emergent
      cause of infection in the immunocompromized population, especially in the solid
      organ transplant recipients. Herein the authors report a clinical case of a liver
      transplanted patient suffering a cutaneous co-existent infection with A.
      alternata as well as A. infectoria. To our knowledge this is the first case of
      cutaneous concomitant infection due to those two species reported not only in
      Portugal but also worldwide. The patient was treated with surgical excision of
      the lesions and oral itraconazol without relapse. 

PMID- 25750856
TI  - From respiratory sensitization to food allergy: Anaphylactic reaction after
      ingestion of mushrooms (Agaricus bisporus).
AB  - We report a case of a 38-year-old mold-allergic patient who developed episodes of
      generalized urticaria and systemic anaphylactic shock immediately after ingesting
      button mushrooms. A manganese-dependent superoxide dismutase (MnSOD) and a NADP
      dependent mannitol dehydrogenase (MtDH) from Agaricus bisporus mushroom were
      identified as patient-specific IgE-binding proteins. Cross-reactivity between A.
      bisporus MnSOD and mold aeroallergens was confirmed. We conclude that prior
      sensitization to mold aeroallergens might explain severe food reactions to cross
      reacting homologs mushroom proteins. 

PMID- 25750857
TI  - Hematogenous dissemination of Candida dubliniensis causing spondylodiscitis and
      spinal abscess in a HIV-1 and HCV-coinfected patient.
AB  - We report a case of spondylodiscitis and spinal abscess following haematogenous
      dissemination of the emerging yeast Candida dubliniensis in a human
      immunodeficiency virus-1 (HIV-1) and hepatitis C virus (HCV)-coinfected patient.
      Although C. dubliniensis is considered less virulent compared to its closest
      known relative Candida albicans, reports of severe fungal infections are
      increasing. This case indicates that the pathogenicity of C. dubliniensis may be
      higher than previously believed. Therefore fungal infections caused by this
      dimorph fungus should be kept in mind in immunocompromised patients with
      spondylodiscitis and spinal abscess. 

PMID- 25750858
TI  - Image-guided Interstitial Photodynamic Therapy for Squamous Cell Carcinomas:
      Preclinical investigation.
AB  - OBJECTIVE: Photodynamic therapy (PDT) is a clinically approved minimally invasive
      treatment for cancer. In this preclinical study, using an imaging-guided
      approach, we examined the potential utility of PDT in the management of bulky
      squamous cell carcinomas (SCCs). METHODS: To mimic bulky oropharyngeal cancers
      seen in the clinical setting, intramuscular SCCs were established in six-to-eight
      week old female C3H mice. Animals were injected with the photosensitizer, 2
      [hexyloxyethyl]-2-devinyl pyropheophorbide-a (HPPH; 0.4 MUmol/kg, i.v.) and
      tumors were illuminated 24 hours post injection with 665 nm light. PDT as a
      single treatment modality was administered by surface illumination or by
      interstitial placement of fibers (iPDT). Magnetic resonance imaging was used to
      guide treatment and assess tumor response to PDT along with correlative
      histopathologic assessment. RESULTS: Interstitial HPPH-PDT resulted in a marked
      change on T2 maps 24 hours post treatment compared to untreated controls or
      transcutaneous illumination. Corresponding apparent diffusion coefficient maps
      also showed hyperintense areas in tumors following iPDT suggestive of effective
      photodynamic cell kill. Histologic sections (H&E) confirmed presence of extensive
      tumor necrosis following iPDT. CONCLUSIONS: These results highlight the potential
      utility of PDT in the treatment of bulky oropharyngeal cancers. The findings of
      our study also demonstrate the utility of MRI as a non-invasive tool for mapping
      of early tissue response to PDT.

PMID- 25750859
TI  - Low frequency of Y anomaly detected in Australian Brahman cow-herds.
AB  - Indicine cattle have lower reproductive performance in comparison to taurine. A
      chromosomal anomaly characterized by the presence Y markers in females was
      reported and associated with infertility in cattle. The aim of this study was to
      investigate the occurrence of the anomaly in Brahman cows. Brahman cows (n = 929)
      were genotyped for a Y chromosome specific region using real time-PCR. Only six
      out of 929 cows had the anomaly (0.6%). The anomaly frequency was much lower in
      Brahman cows than in the crossbred population, in which it was first detected. It
      also seems that the anomaly doesn't affect pregnancy in the population. Due to
      the low frequency, association analyses couldn't be executed. Further, SNP signal
      of the pseudoautosomal boundary region of the Y chromosome was investigated using
      HD SNP chip. Pooled DNA of "non-pregnant" and "pregnant" cows were compared and
      no difference in SNP allele frequency was observed. Results suggest that the
      anomaly had a very low frequency in this Australian Brahman population and had no
      effect on reproduction. Further studies comparing pregnant cows and cows that
      failed to conceive should be executed after better assembly and annotation of the
      Y chromosome in cattle. 

PMID- 25750860
TI  - Start codon targeted (SCoT) polymorphism reveals genetic diversity in wild and
      domesticated populations of ramie (Boehmeria nivea L. Gaudich.), a premium
      textile fiber producing species.
AB  - Twenty-four start codon targeted (SCoT) markers were used to assess genetic
      diversity and population structure of indigenous, introduced and domesticated
      ramie (Boehmeria nivea L. Gaudich.). A total of 155 genotypes from five
      populations were investigated for SCoT polymorphism, which produced 136 amplicons
      with 87.5% polymorphism. Polymorphism information content and resolving power of
      the SCoT markers were 0.69 and 3.22, respectively. The Indian ramie populations
      exhibited high SCoT polymorphism (> 50%), high genetic differentiation (GST =
      0.27) and moderate gene flow (Nm = 1.34). Analysis of molecular variance
      identified significant differences for genetic polymorphism among the populations
      explaining 13.1% of the total variation. The domesticated population exhibited
      higher genetic polymorphism and heterozygosity compared to natural populations.
      Cluster analysis supported population genetic analysis and suggested close
      association between introduced and domesticated genotypes. The present study
      shows effectiveness of employing SCoT markers in a cross pollinated heterozygous
      species like Boehmeria, and would be useful for further studies in population
      genetics, conservation genetics and cultivar improvement. 

PMID- 25750861
TI  - Mutation analysis of methylmalonyl CoA mutase gene exon 2 in Egyptian families:
      Identification of 25 novel allelic variants.
AB  - Methylmalonic aciduria (MMA) is an autosomal recessive disorder of methylmalonate
      and cobalamin (cbl; vitamin B12) metabolism. It is an inborn error of organic
      acid metabolism which commonly results from a defect in the gene encoding the
      methylmalonyl-CoA mutase (MCM) apoenzyme. Here we report the results of mutation
      study of exon 2 of the methylmalonyl CoA mutase (MUT) gene, coding MCM residues
      from 1 to 128, in ten unrelated Egyptian families affected with methylmalonic
      aciduria. Patients were presented with a wide-anion gap metabolic acidosis. The
      diagnosis has established by the measurement of C3 (propionylcarnitine) and C3:C2
      (propionylcarnitine/acetylcarnitine) in blood by using liquid chromatography
      tandem mass spectrometry (LC/MS-MS) and was confirmed by the detection of an
      abnormally elevated level of methylmalonic acid in urine by using gas
      chromatography-mass spectrometry (GC/MS) and isocratic cation exchange high
      performance liquid-chromatography (HPLC). Direct sequencing of gDNA of the MUT
      gene exon 2 has revealed a total of 26 allelic variants: ten of which were
      intronic, eight were located upstream to the exon 2 coding region, four were
      novel modifications predicted to affect the splicing region, three were novel
      mutations within the coding region: c.15G > A (p.K5K), c.165C > A (p.N55K) and
      c.7del (p.R3EfsX14), as well as the previously reported mutation c.323G > A
      (p.R108H). 

PMID- 25750862
TI  - From black box to toolbox: Outlining device functionality, engagement activities,
      and the pervasive information architecture of mHealth interventions.
AB  - mHealth interventions that deliver content via mobile phones represent a
      burgeoning area of health behavior change. The current paper examines two themes
      that can inform the underlying design of mHealth interventions: (1) mobile device
      functionality, which represents the technological toolbox available to
      intervention developers; and (2) the pervasive information architecture of
      mHealth interventions, which determines how intervention content can be delivered
      concurrently using mobile phones, personal computers, and other devices. We posit
      that developers of mHealth interventions will be better able to achieve the
      promise of this burgeoning arena by leveraging the toolbox and functionality of
      mobile devices in order to engage participants and encourage meaningful behavior
      change within the context of a carefully designed pervasive information
      architecture.

PMID- 25750865
TI  - Short-term effect of botulinum toxin a injection on spastic equinovarus foot in
      cerebral palsy patients: a study using the foot pressure measurement system.
AB  - OBJECTIVE: To evaluate the therapeutic effect of botulinum toxin A (BTX-A)
      injection on spastic gastrocnemius (GCM) and tibialis posterior muscles (TPo) by
      using the foot pressure measurement system (FPMS). METHODS: Eighteen ambulatory
      CP patients were recruited in this study. BTX-A was injected into the GCM at a
      dose of 6-12 units/kg and TPo at a dose of 4-9 units/kg according to the severity
      of equinus and varus deformity. Foot contact pattern, pressure time integral
      (PTI), coronal index using the FPMS and Modified Ashworth Scale (MAS), and visual
      inspection of gait pattern were used for evaluation of the therapeutic effect of
      BTX-A injection. Clinical and FPMS data were statistically analyzed according to
      the muscle group. RESULTS: A significant decrease in the MAS score of the GCM and
      TPo was observed, and spastic equinovarus pattern during gait showed improvement
      after injection. The GCM+TPo injection group showed a significant decrease in
      forefoot, lateral forefoot pad, and lateral column PTI, and a significant
      increase in hindfoot PTI and coronal index. In the GCM only injection group,
      forefoot PTI and lateral column PTI were significantly decreased and hindfoot PTI
      was significantly increased. The TPo only injection group showed a significant
      decrease in lateral column PTI and a significant increase in the coronal index.
      Change in PTI in the hindfoot showed a significant correlation with the change in
      MAS score of the GCM. Change in PTI of the lateral column and coronal index
      showed a significant correlation with the change in MAS score of the TPo.
      CONCLUSION: The FPMS demonstrated the quantitative therapeutic effect of BTX-A on
      abnormal pressure distribution in equinovarus foot in detail. The FPMS can be a
      useful additional tool for evaluation of the effect of BTX-A injection.

PMID- 25750863
TI  - Threading the cloak: palliative care education for care providers of adolescents
      and young adults with cancer.
AB  - Medical providers are trained to investigate, diagnose, and treat cancer. Their
      primary goal is to maximize the chances of curing the patient, with less training
      provided on palliative care concepts and the unique developmental needs inherent
      in this population. Early, systematic integration of palliative care into
      standard oncology practice represents a valuable, imperative approach to
      improving the overall cancer experience for adolescents and young adults (AYAs).
      The importance of competent, confident, and compassionate providers for AYAs
      warrants the development of effective educational strategies for teaching AYA
      palliative care. Just as palliative care should be integrated early in the
      disease trajectory of AYA patients, palliative care training should be integrated
      early in professional development of trainees. As the AYA age spectrum represents
      sequential transitions through developmental stages, trainees experience changes
      in their learning needs during their progression through sequential phases of
      training. This article reviews unique epidemiologic, developmental, and
      psychosocial factors that make the provision of palliative care especially
      challenging in AYAs. A conceptual framework is provided for AYA palliative care
      education. Critical instructional strategies including experiential learning,
      group didactic opportunity, shared learning among care disciplines, bereaved
      family members as educators, and online learning are reviewed. Educational issues
      for provider training are addressed from the perspective of the trainer, trainee,
      and AYA. Goals and objectives for an AYA palliative care cancer rotation are
      presented. Guidance is also provided on ways to support an AYA's quality of life
      as end of life nears.

PMID- 25750866
TI  - Correlation of foot posture index with plantar pressure and radiographic
      measurements in pediatric flatfoot.
AB  - OBJECTIVE: To investigate the correlation between the Foot Posture Index (FPI)
      (including talar head palpation, curvature at the lateral malleoli,
      inversion/eversion of the calcaneus, talonavicular bulging, congruence of the
      medical longitudinal arch, and abduction/adduction of the forefoot on the rare
      foot), plantar pressure distribution, and pediatric flatfoot radiographic
      findings. METHODS: Nineteen children with flatfoot (age, 9.32+/-2.67 years) were
      included as the study group. Eight segments of plantar pressure were measured
      with the GaitView platform pressure pad and the FPI was measured in children. The
      four angles were measured on foot radiographs. We analyzed the correlation
      between the FPI, plantar pressure characteristics, and the radiographic angles in
      children with flatfoot. RESULTS: The ratio of hallux segment pressure and the
      second through fifth toe segment pressure was correlated with the FPI (r=0.385,
      p=0.017). The FPI was correlated with the lateral talo-first metatarsal angle
      (r=0.422, p=0.008) and calcaneal pitch (r=-0.411, p=0.01). CONCLUSION: Our
      results show a correlation between the FPI and plantar pressure. The FPI and
      pediatric flatfoot radiography are useful tools to evaluate pediatric flatfoot.

PMID- 25750867
TI  - Factors that affect the rehabilitation duration in patients with congenital
      muscular torticollis.
AB  - OBJECTIVE: To determine which factors affect the rehabilitation duration in
      patients with congenital muscular torticollis (CMT) and to predict the duration
      of rehabilitation and prognosis. METHODS: One hundred and eighteen patients (79
      males and 39 females) who were diagnosed with CMT and received physical therapy
      were enrolled in this study. We retrospectively reviewed the information in terms
      of sex, gestational age, birth weight, methods of delivery, fetal presentation,
      age at diagnosis, the affected sternocleidomastoid (SCM) muscle site, SCM muscle
      thickness, ratio of muscle thickness on the affected side to that on the
      unaffected side (called the 'abnormal/normal [A/N] ratio'), and range of motion
      for cervical rotation and side bending. RESULTS: The SCM muscle thickness and A/N
      ratio had a positive linear relationship with the rehabilitation duration.
      Patients who were in the breech position needed longer rehabilitation. The birth
      weight and age at diagnosis were negatively correlated with the rehabilitation
      duration. However, the cervical range of motion, mass site, sex, gestational age,
      and methods of delivery were not correlated with the rehabilitation duration.
      CONCLUSION: Patients with a thicker SCM, lower birth weight, and history of
      breech delivery had a longer rehabilitation duration.

PMID- 25750868
TI  - The effect of treadmill exercise on gait efficiency during overground walking in
      adults with cerebral palsy.
AB  - OBJECTIVE: To investigate the effect of treadmill walking exercise as a treatment
      method to improve gait efficiency in adults with cerebral palsy (CP) and to
      determine gait efficiency during overground walking after the treadmill walking
      exercise. METHODS: Fourteen adults with CP were recruited in the experimental
      group of treadmill walking exercise. A control group of 7 adults with CP who
      attended conventional physical therapy were also recruited. The treadmill walking
      exercise protocol consisted of 3-5 training sessions per week for 1-2 months
      (total 20 sessions). Gait distance, velocity, VO2, VCO2, O2 rate (mL/kg.min), and
      O2 cost (mL/kg.m) were assessed at the beginning and at the end of the treadmill
      walking exercise. The parameters were measured by KB1-C oximeter. RESULTS: After
      the treadmill walking exercise, gait distance during overground walking up to 6
      minutes significantly increased from 151.29+/-91.79 to 193.93+/-79.01 m, and gait
      velocity increased from 28.09+/-14.29 to 33.49+/-12.69 m/min (p<0.05). Energy
      efficiency evaluated by O2 cost during overground walking significantly improved
      from 0.56+/-0.36 to 0.41+/-0.18 mL/kg.m (p<0.05), whereas O2 rate did not improve
      significantly after the treadmill walking exercise. On the other hand, gait
      velocity and O2 cost during overground walking were not significantly changed in
      the control group. CONCLUSION: Treadmill walking exercise improved the gait
      efficiency by decreased energy expenditure during overground walking in adults
      with CP. Therefore, treadmill walking exercise can be an important method for
      gait training in adults with CP who have higher energy expenditure.

PMID- 25750869
TI  - Determination of injection site in flexor digitorum longus for effective and safe
      botulinum toxin injection.
AB  - OBJECTIVE: To determine the optimal injection site in the flexor digitorum longus
      (FDL) muscle for effective botulinum toxin injection. METHODS: Fourteen specimens
      from eight adult Korean cadavers were used in this study. The most proximal
      medial point of the tibia plateau was defined as the proximal reference point;
      the most distal tip of the medial malleolus was defined as the distal reference
      point. The distance of a line connecting the proximal and distal reference points
      was defined as the reference length. The X-coordinate was the distance from the
      proximal reference point to the intramuscular motor endpoint (IME), or motor
      entry point (MEP) on the reference line, and the Y-coordinate was the distance
      from the nearest point from MEP on the medial border of the tibia to the MEP. IME
      and MEP distances from the proximal reference point were evaluated using the raw
      value and the X-coordinate to reference length ratio was determined as a
      percentage. RESULTS: The majority of IMEs were located within 30%-60% of the
      reference length from the proximal reference point. The majority of the MEPs were
      located within 40%-60% of the reference length from the proximal reference point.
      CONCLUSION: We recommend the anatomical site for a botulinum toxin injection in
      the FDL to be within a region 30%-60% of the reference length from the proximal
      reference point.

PMID- 25750870
TI  - Anatomical basis of pronator teres for electromyography needle placement using
      ultrasonography.
AB  - OBJECTIVE: To find the optimal needle insertion site for needle electromyography
      of the pronator teres (PT) muscle among commonly used sites. METHODS: Fifty
      forearms of 25 healthy subjects were evaluated. Four expected needle insertion
      points were designated as follows. Point 0 was positioned at the midpoint between
      the medial epicondyle and medial border of biceps tendon in the elbow crease.
      Points 1, 2, and 3 were located 2 cm, 3.5 cm and 5 cm distal to point 0,
      respectively. We assumed that the thickness of PT and the distances between a
      vertical line from each point to the medial margin of the PT were significant
      parameters for finding the optimal site. Thus, we measured these parameters
      through ultrasonographic examination. RESULTS: In men, the PT was thickest at
      point 2, and in women, at point 1. The distance between the expected needle
      insertion line and medial margin of PT was longest at point 1 in both men and
      women, and was statistically significant compared to points 2 and 3. Both men and
      women had neurovascular bundles located lateral to the expected needle insertion
      line. CONCLUSION: The most appropriate and safe needle electromyographic
      insertional site for the PT is 2-3.5 cm distal to the mid-point between the
      biceps tendon and medial epicondyle in the elbow crease and the needle should be
      inserted upward and medial.

PMID- 25750871
TI  - Ultrasound-guided lateral femoral cutaneous nerve conduction study.
AB  - OBJECTIVE: To verify the utility of the lateral femoral cutaneous nerve (LFCN)
      ultrasound-guided conduction technique compared to that of the conventional nerve
      conduction technique. METHODS: Fifty-eight legs of 29 healthy participants (18
      males and 11 females; mean age, 42.7+/-14.9 years) were recruited. The
      conventional technique was performed bilaterally. The LFCN was localized by
      ultrasound. Cross-sectional area (CSA) of the LFCN and the distance between the
      anterior superior iliac spine (ASIS) and the LFCN was measured. The nerve
      conduction study was repeated with the corrected cathode location. Sensory nerve
      action potential (SNAP) amplitudes of the LFCN were recorded and compared between
      the ultrasound-guided and conventional techniques. RESULTS: Mean body mass index
      of the participants was 23.7+/-3.5 kg/m(2), CSA was 4.2+/-1.9 mm(2), and the
      distance between the ASIS and LFCN was 5.6+/-1.7 mm. The mean amplitude values
      were 6.07+/-0.52 uV and 6.66+/-0.54 uV using the conventional and ultrasound
      guided techniques, respectively. The SNAP amplitude of the LFCN using the
      ultrasound-guided technique was significantly larger than that recorded using the
      conventional technique. CONCLUSION: Correcting the stimulation position using the
      ultrasound-guided technique helped obtain increased SNAP amplitude.

PMID- 25750872
TI  - Branching patterns of medial and inferior calcaneal nerves around the tarsal
      tunnel.
AB  - OBJECTIVE: To demonstrate the bifurcation pattern of the tibial nerve and its
      branches. METHODS: Eleven legs of seven fresh cadavers were dissected. The
      reference line for the bifurcation point of tibial nerve branches was an
      imaginary horizontal line passing the tip of the medial malleolus. The distances
      between the reference line and the bifurcation points were measured. The
      bifurcation branching patterns were categorized as type I, the pattern in which
      the medial calcaneal nerve (MCN) branched most proximally; type II, the pattern
      in which the three branches occurred at the same point; and type III, in which
      MCN branched most distally. RESULTS: There were seven cases (64%) of type I,
      three cases (27%) of type III, and one case (9%) of type II. The median MCN
      branching point was 0.2 cm (range, -1 to 3 cm). The median bifurcation points of
      the lateral plantar nerves and inferior calcaneal nerves was -0.6 cm (range, -1.5
      to 1 cm) and -2.5 cm (range, -3.5 to -1 cm), respectively. CONCLUSION: MCN
      originated from the tibial nerve in most cases, and plantar nerves were
      bifurcated below the medial malleolus. In all cases, inferior calcaneal nerves
      originated from the lateral plantar nerve. These anatomical findings could be
      useful for performing procedures, such as nerve block or electrophysiologic
      studies.

PMID- 25750873
TI  - Feasibility of Applying the Extended ICF Core Set for Stroke to Clinical Settings
      in Rehabilitation: A Preliminary Study.
AB  - OBJECTIVE: To evaluate the potential feasibility of application of the extended
      International Classification of Functioning, Disability and Health (ICF) Core Set
      for stroke. METHODS: We retrospectively reviewed the medical records of 40 stroke
      outpatients (>6 months after onset) admitted to the Department of Rehabilitation
      Medicine for comprehensive rehabilitation. Clinical information of the patients
      were respectively evaluated to link to the 166 second-level categories of the
      extended ICF Core Set for stroke. RESULTS: Clinical information could be linked
      to 111 different ICF categories, 58 categories of the body functions component,
      eight categories of the body structures component, 38 categories of the
      activities and participation component, and seven categories of the environmental
      factors component. CONCLUSION: The body functions component might be feasible for
      application of the extended ICF Core Set for stroke to clinical settings. The
      activities and participation component and environmental factors component may
      not be directly applied to clinical settings without additional evaluation tools
      including interview and questionnaire.

PMID- 25750874
TI  - The relationship between initial trunk performances and functional prognosis in
      patients with stroke.
AB  - OBJECTIVE: To confirm the relationship between initial trunk performance and
      functional outcomes according to gait ability, and whether initial trunk
      performance is of predictive value in terms of functional prognosis in patients
      with stroke. METHODS: We reviewed 135 patients who suffered from stroke. Trunk
      performance of the patients was evaluated using the Trunk Impairment Scale (TIS).
      The patients were divided into 2 groups according to gait ability at initial
      stage of stroke. Correlation analyses were performed to assess relationship
      between initial TIS and functional outcomes. We also evaluated the relationship
      between initial TIS and the Korean version of Modified Barthel Index (K-MBI)
      subitems. Finally, stepwise multiple regression analyses were performed to
      examine the predictive validity of initial TIS and its subscales with functional
      outcomes. RESULTS: For both groups, initial TIS was correlated with K-MBI and
      Functional Ambulation Categories at 4 weeks after stroke; however, the
      relationship did not remain stable at 6 months in ambulatory patients. All K-MBI
      subitems, which were associated with trunk movement, as well as others about
      basic skills was correlated with initial TIS. Finally, when of subscales TIS,
      dynamic sitting balance (TIS-D) was included in by stepwise multiple regression
      analyses, high proportion of the explained variance was represented. CONCLUSION:
      The strong relationship between trunk performance and functional outcomes in
      patients with stroke emphasizes the importance of trunk rehabilitation. Indeed,
      an evaluation of a patient's initial TIS after stroke, especially TIS-D, could be
      helpful in predicting patient's functional prognosis.

PMID- 25750875
TI  - The effect of post-stroke depression on rehabilitation outcome and the impact of
      caregiver type as a factor of post-stroke depression.
AB  - OBJECTIVE: To evaluate the effect of post-stroke depression (PSD) on
      rehabilitation outcome and to investigate the risk factors of PSD, especially,
      the role of caregivers type (family or professional) in subacute stroke patients.
      METHODS: Two hundred twenty-six stroke patients were enrolled retrospectively.
      All the subjects' basic characteristics, Korean version of the Beck Depression
      Inventory (K-BDI), Korean version of the Modified Barthel Index (K-MBI), and the
      modified Rankin Scale (mRS) were recorded when the patient was transferred into
      the Department of Rehabilitation Medicine and at the time of discharge. The
      results were statistically analyzed by using SPSS ver. 20.0. RESULTS: The
      patients' K-BDI score showed a significantly negative association with K-MBI at
      discharge (beta=-0.473, p<0.001) and a significantly positive association with
      the mRS score at discharge (beta=0.316, p<0.001). Patients with lesions on the
      left hemisphere (odds ratio [OR], 3.882; 95% confidence interval [CI], 1.726
      8.733) and professional caregiver support (OR, 0.028; 95% CI, 0.012-0.065) had a
      higher rate of depression. CONCLUSION: Depression was prevalent in stroke
      patients, and it had a negative effect on patients' functional outcome. Patients
      who had a lesion on the right hemisphere had less depression. The type of
      caregiver was related to the incidence of subacute PSD, and family caregivers
      were found to lower the frequency of stroke patients' depression.

PMID- 25750876
TI  - The effect of dual-task training on balance and cognition in patients with
      subacute post-stroke.
AB  - OBJECTIVE: To investigate the effect of dual-task training on the recovery of
      balance ability and cognitive function in patients with subacute stroke. METHODS:
      Twenty patients (12 males and eight females; average age, 59.70 years) with
      subacute stroke were enrolled in this study. All participants were randomly
      assigned to one of two groups, the dual-task group (n=10) or the control group
      (n=10). The dual task was simultaneous balance and cognitive training using the
      BioRescue. All patients were evaluated with posturographic parameters and the
      Berg Balance Scale for balance ability, a computerized neuropsychological test
      and the Korean version of the Mini-Mental State Examination for cognitive
      function, the Fugl-Meyer Assessment for motor function, and the Korean-Modified
      Barthel Index for activities of daily living (ADL) function before and after 4
      weeks of rehabilitation. RESULTS: The dual-task group showed significant
      improvements in the pressure of the weight distribution index (WDI), surface
      area, and length of the stability index during the eyes-open condition; surface
      area of the limit of stability (LOS) on the hemiparetic and intact sides, and the
      auditory continuous performance test and backward visual span test after
      rehabilitation. Although no significant difference was observed for the changes
      in balance ability or cognitive, motor, and ADL functions between the groups,
      changes in the WDI pressure during the eyes-open condition and in the area ratio
      of LOS (hemiparetic/intact) showed a tendency to improve in the dual-task group.
      CONCLUSION: Our findings suggest that dual-task training could be as effective as
      conventional balance training for improving balance and cognition in subacute
      post-stroke patients.

PMID- 25750877
TI  - Effect of regular exercise on cardiopulmonary fitness in males with spinal cord
      injury.
AB  - OBJECTIVE: To evaluate the cardiopulmonary endurance of subjects with spinal cord
      injury by measuring the maximal oxygen consumption with varying degrees of spinal
      cord injury level, age, and regular exercise. METHODS: We instructed the subjects
      to perform exercises using arm ergometer on healthy adults at 20 years of age or
      older with spinal cord injury, and their maximal oxygen consumption (VO2max) was
      measured with a metabolic measurement system. The exercise proceeded stepwise
      according to the exercise protocol and was stopped when the subject was exhausted
      or when VO2 reached an equilibriu. RESULTS: Among the 40 subjects, there were 10
      subjects with cervical cord injury, 27 with thoracic cord injury, and 3 with
      lumbar cord injury. Twenty-five subjects who were exercised regularly showed
      statistically higher results of VO2max than those who did not exercise regularly.
      Subjects with cervical injury showed statistically lower VO2max than the subjects
      with thoracic or lumbar injury out of the 40 subjects with neurologic injury. In
      addition, higher age showed a statistically lower VO2max. Lastly, the regularly
      exercising paraplegic group showed higher VO2max than the non-exercising
      paraplegic group. CONCLUSION: There are differences in VO2max of subjects with
      spinal cord injury according to the degree of neurologic injury, age, and whether
      the subject participates in regular exercise. We found that regular exercise
      increased the VO2max in individuals with spinal cord injury.

PMID- 25750878
TI  - Correlates of bone mineral density and sagittal spinal balance in the aged.
AB  - OBJECTIVE: To investigate the relationship between bone mineral density (BMD) and
      sagittal spinal balance in the Korean elderly population. METHODS: The
      retrospective study included subjects aged 60 years and above, who had whole
      spine lateral radiography and dual-energy X-ray absorptiometry (DEXA) within a
      year's gap between each other. Sagittal vertical axis (SVA) for evaluation of
      sagittal spinal balance and five spinopelvic parameters were measured through
      radiography. The presence of compression fracture was identified. Correlations of
      BMD T-scores with SVA and with the spinopelvic parameters were assessed using
      Pearson correlation coefficient (PCC). Linear regression analyses were performed
      between SVA and the clinical and radiologic variables. RESULTS: One hundred
      twenty-two subjects (42 males and 80 females; mean age, 69.93+/-5.5 years) were
      included in the study. BMD, femur or spine, was not correlated with SVA or any
      spinopelvic parameters in both genders (PCC<+/-0.2), except that spine BMD in men
      was associated with sacral slope. Univariate regression analysis revealed
      association between SVA and lumbar lordosis, pelvic tilt, and compression
      fractures in both genders; it was also associated with age and pelvic incidence
      in females and with sacral slope in males. Multivariate linear regression model
      showed lumbar lordosis and compression fracture as variables affecting SVA in
      both sexes; pelvic incidence was another factor affecting SVA in women only.
      CONCLUSION: BMD was not associated with sagittal spinal balance in the aged.
      Sagittal spinal balance was explained partly by lumbar lordosis and compression
      fracture. Further study is warranted to understand progression of sagittal
      imbalance with age.

PMID- 25750879
TI  - Pain-related evoked potential in healthy adults.
AB  - OBJECTIVE: To investigate the normal data of pain-related evoked potentials
      (PREP) elicited with a concentric surface electrode among normal, healthy adults
      and the relationship between PREP and pain intensity. METHODS: Sixty healthy
      volunteers (22 men and 38 women; aged 36.4+/-10.7 years; height, 165.4+/-7.8 cm)
      were enrolled. Routine nerve conduction study (NCS) was done to measure PREP
      following electrical stimulation of hands (C7 dermatome) and feet (L5 dermatome).
      Negative peak (N), positive peak (P) latencies, peak to peak (NP) amplitudes,
      conduction velocity (CV), and verbal rating scale (VRS) score were obtained.
      Linear regression analysis tested for significant relevance between variables of
      PREP and VRS score. RESULTS: Normal NCS results were obtained in all subjects. N
      latency of hand PREP was 163.8 +/-40.0 ms (right) and 161.0+/-39.9 ms (left). N
      latency of foot PREP was 178.0+/-43.9 ms (right), 180.4+/-43.4 ms (left). NP
      amplitude of hands was 20.6+/-10.6 uV (right) and 21.9+/-11.6 uV (left). NP
      amplitude of feet was 18.8+/-8.3 uV (right) and 19.0+/-8.4 uV (left). The
      calculated CV was 13.2+/-4.7 m/s and VRS score was 3.8+/-1.0. A highly
      significant positive correlation was evident between VRS score and NP amplitude
      (y=0.1069x+1.781, r=0.877, n=60, p<0.0001). CONCLUSION: PREP among normal,
      healthy adults revealed a statistically significant correlation between PREP
      amplitude and VRS score.

PMID- 25750880
TI  - Predictive value of sympathetic skin response in diagnosing complex regional pain
      syndrome: a case-control study.
AB  - OBJECTIVE: To investigate the predictive value of the sympathetic skin response
      (SSR) in diagnosing complex regional pain syndrome (CRPS) by comparing three
      diagnostic modalities-SSR, three-phasic bone scans (TPBS), and thermography.
      METHODS: Thirteen patients with severe limb pain were recruited. Among them, 6
      were diagnosed with CRPS according to the proposed revised CRPS clinical
      diagnostic criteria described by the International Association for the Study of
      Pain. SSR was measured in either the hands or feet bilaterally and was considered
      abnormal when the latency was prolonged. A positive TPBS finding was defined as
      diffuse increased tracer uptake on the delayed image. Thermographic findings were
      considered positive if a temperature asymmetry greater than 1.00C was detected
      between the extremities. RESULTS: Five of 6 CRPS patients showed prolonged
      latency on SSR (83% sensitivity). TPBS was positive in the 5 CRPS patients who
      underwent TPBS (100% sensitivity). Thermography was positive in 4 of 5 CRPS
      patients who underwent the procedure (80% sensitivity). The remaining 7 non-CRPS
      patients differed on examination. SSR latencies within normal limit were noted in
      4 of 7 non-CRPS patients (57% specificity). Results were negative in 4 of 5 non
      CRPS patients who underwent TPBS (80% specificity), and negative in 3 of 5 non
      CRPS patients who underwent thermography (60% specificity). CONCLUSION: SSR may
      be helpful in detecting CRPS.

PMID- 25750881
TI  - Monomelic amyotrophy (hirayama disease) with upper motor neuron signs: a case
      report.
AB  - Monomelic amyotrophy (MMA), also known as Hirayama disease, is a sporadic
      juvenile muscular atrophy in the distal upper extremities. This disorder rarely
      involves proximal upper extremities and presents minimal sensory symptoms with no
      upper motor neuron (UMN) signs. It is caused by anterior displacement of the
      posterior dural sac and compression of the cervical cord during neck flexion. An
      18-year-old boy visited our clinic with a 5-year history of left upper extremity
      pain and slowly progressive weakness affecting the left shoulder. Atrophy was
      present in the left supraspinatus and infraspinatus. On neurological examination,
      positive UMN signs were evident in both upper and lower extremities.
      Electrodiagnostic study showed root lesion involving the fifth to seventh
      cervical segment of the cord with chronic and ongoing denervation in the fifth
      and sixth cervical segment innervated muscles. Cervical magnetic resonance
      imaging (MRI) showed asymmetric cord atrophy apparent in the left side and
      intramedullary high signal intensity along the fourth to sixth cervical vertebral
      levels. With neck flexion, cervical MRI revealed anterior displacement of
      posterior dural sac, which results in the cord compression of those segments. The
      mechanisms of myelopathy in our patient seem to be same as that of MMA. We report
      a MMA patient involving proximal limb with UMN signs in biomechanical concerns
      and discuss clinical importance of cervical MRI with neck flexion. The case
      highlights that clinical variation might cause misdiagnosis. 

PMID- 25750882
TI  - Correction of camptocormia using a cruciform anterior spinal hyperextension brace
      and back extensor strengthening exercise in a patient with Parkinson disease.
AB  - Parkinson disease, one of the most common neurodegenerative diseases, is
      characterized by cardinal motor features including bradykinesia, rigidity,
      resting tremor, postural instability, freezing gait, and fatigue. Of these,
      postural instability in the form of hyperflexion of the thoracolumbar spine upon
      standing and walking that disappears on recumbent positioning is called
      camptocormia. Many different trials have been conducted on the treatment of
      camptocormia, including physiotherapy, corsets, medications, and deep brain
      stimulation. However, there is insufficient evidence as to which treatment
      modality is the most valid in terms of effectiveness, cost, safety, and patient
      satisfaction. In this study, we present a patient whose symptom of camptocormia
      was effectively resolved using a cruciform anterior spinal hyperextension (CASH)
      brace and back extensor strengthening exercise which was modified through follow
      ups based on a short-term outpatient setting for proper application with minimal
      discomfort. The patient was satisfied with the amount of correction provided by
      the brace and exercise. 

PMID- 25750883
TI  - Conversion of percutaneous endoscopic gastrostomy to gastrojejunostomy under
      fluoroscopic guidance for treatment of gastrocutaneous fistula.
AB  - Persistent enterocutaneous fistula after the removal of a gastrostomy tube is an
      unusual complication of percutaneous endoscopic gastrostomy (PEG). The following
      case report describes an 81-year-old man diagnosed with stroke and dysphagia in
      May 2008. The patient had been using a PEG since 2008, and PEG site infection
      occurred in June 2013. The PEG tube was removed and a new PEG tube was inserted.
      Thereafter, formation of gastrocutaneous fistula around the previous infected PEG
      site was observed. The fistula was refractory to medical management, accompanied
      by long duration of fasting and peripheral alimentation. Therefore,
      gastrojejunostomy tube insertion via the previously inserted PEG tube was
      performed, under fluoroscopic guidance; this mode of management was successful.
      For patients who have a gastrocutaneous fistula, gastrojejunostomy tube insertion
      via the pre-existing PEG tube is a safe and effective alternative management for
      enteral feeding. 

PMID- 25750884
TI  - Hepatic encephalopathy with corticospinal tract involvement demonstrated by
      diffusion tensor tractography.
AB  - A 50-year-old man with liver cirrhosis and esophageal varix for 3 years was
      diagnosed with hematemesis and treated for a bleeding varix. However, bleeding
      recurred 11 days later, and he developed drowsiness with left hemiparesis. His
      left upper and lower extremity muscle strengths based on the manual muscle test
      at the onset were grade 2/5 and 1/5, respectively. The Babinski sign was
      positive. His serum ammonia level was elevated to 129.9 ug/dL (normal, 20-80
      ug/dL). Magnetic resonance imaging revealed restriction on diffusion and T2
      hyperintensities with decreased apparent diffusion coefficient values in the
      bilateral frontoparietooccipital cortex. The effect was more severe in the right
      hemisphere and right parietooccipital cortices, which were compatible with
      hepatic encephalopathy. Although the patient's mental status recovered,
      significant left-sided weakness and sensory deficit persisted even after 6
      months. Diffusion tensor tractography (DTT) performed 3 months post-onset showed
      decreased volume of the right corticospinal tract. We reported a patient with
      hepatic encephalopathy involving the corticospinal tract by DTT. 

PMID- 25750885
TI  - Concomitant acute transverse myelitis and sensory motor axonal polyneuropathy in
      two children: two case reports.
AB  - Acute transverse myelitis (ATM) is an upper motor neuron disease of the spinal
      cord, and concomitant association of peripheral polyneuropathy, particularly the
      axonal type, is rarely reported in children. Our cases presented with ATM
      complicated with axonal type polyneuropathy. Axonal type polyneuropathy may be
      caused by acute motor-sensory axonal neuropathy (AMSAN) or critical illness
      polyneuropathy and myopathy (CIPNM). These cases emphasize the need for nerve and
      muscle biopsies to make the differential diagnosis between AMSAN and CIPNM in
      patients with ATM complicated with axonal polyneuropathy. 

PMID- 25750886
TI  - Traumatic atypical tetraplegia without radiologic abnormalities including
      magnetic resonance imaging in an adult: a case report.
AB  - Although spinal cord injury without radiographic abnormality (SCIWORA) literally
      refers to the specific type of spinal cord injury, however, some extents of
      spinal cord injuries can be detected by magnetic resonance imaging (MRI) in most
      of cases. We introduce an atypical case of spinal cord injury without radiologic
      abnormality. A 42-year-old male tetraplegic patient underwent MRI and computed
      tomography, and no specific lesions were found in any segments of the spinal
      cord. Moreover, the tetraplegic patient showed normal urodynamic function despite
      severe paralysis and absent somatosensory evoked potentials from the lower limbs.

PMID- 25750887
TI  - Novel information on anatomic factors causing grasp reflex in frontal lobe
      infarction: a case report.
AB  - We report a patient with a severe limitation of function in the right hand
      resulting from grasp reflex following a stroke affecting the left anterior
      cerebral artery region. We describe, using diffusion tensor tractography (DTT), a
      disconnection between the bilateral frontal lobes via the corpus callosum. The
      patient could not control his right hand at all, even though his bilateral
      corticospinal tracts were intact. We noted that over the infarcted lesion on DTT,
      the white matter was invisible from the corpus callosum to the prefrontal cortex.
      These findings reflected a unique pattern of white-matter disconnection between
      the ipsilateral medial frontal lobe and ipsilateral and contralateral frontal
      cortex causing hand function deterioration in the form of severe grasp reflex. 

PMID- 25750888
TI  - Periprosthetic fractures following total knee arthroplasty.
AB  - Periprosthetic fractures after total knee arthroplasty may occur in any part of
      the femur, tibia and patella, and the most common pattern involves the
      supracondylar area of the distal femur. Supracondylar periprosthetic fractures
      frequently occur above a well-fixed prosthesis, and risk factors include anterior
      femoral cortical notching and use of the rotational constrained implant.
      Periprosthetic tibial fractures are frequently associated with loose components
      and malalignment or malposition of implants. Fractures of the patella are much
      less common and associated with rheumatoid arthritis, use of steroid,
      osteonecrosis and malalignment of implants. Most patients with periprosthetic
      fractures around the knee are the elderly with poor bone quality. There are many
      difficulties and increased risk of nonunion after treatment because reduction and
      internal fixation is interfered with by preexisting prosthesis and bone cement.
      Additionally, previous soft tissue injury is another disadvantageous condition
      for bone healing. Many authors reported good clinical outcomes after non
      operative treatment of undisplaced or minimally displaced periprosthetic
      fractures; however, open reduction or revision arthroplasty was required in
      displaced fractures or fractures with unstable prosthesis. Periprosthetic
      fractures around the knee should be prevented by appropriate technique during
      total knee arthroplasty. Nevertheless, if a periprosthetic fracture occurs, an
      appropriate treatment method should be selected considering the stability of the
      prosthesis, displacement of fracture and bone quality. 

PMID- 25750889
TI  - Usefulness of the korean knee score for evaluation of the results of total knee
      arthroplasty.
AB  - PURPOSE: The Korean Knee score (KKS) was designed to reflect the floor-sitting
      lifestyle that necessitates high knee flexion. The purpose of this study is to
      assess whether the KKS reflects the floor-sitting lifestyle more accurately than
      the previously developed Knee Society clinical rating system. In addition, the
      presence of ceiling effects was compared between the two rating systems.
      MATERIALS AND METHODS: Eighty-one consecutive patients (120 knees) who were
      assessed regularly after total knee arthroplasty (TKA) on an outpatient basis
      between January 2012 and December 2012 were enrolled. All patients were asked to
      complete a questionnaire to assess the Knee Society Knee score (KSKS), Knee
      Society Function score (KSFS), and KKS. RESULTS: At the final follow-up, the mean
      KSKS, KSFS, and KKS were 91.2, 86.0, and 70.1, respectively, and the scores were
      similar between the >=125 degrees  maximum flexion group and <125 degrees 
      maximum flexion group. However, the 'floor life' subdomain score of the KKS was
      significantly higher in the >125 degrees  maximum flexion group (15.13 vs. 11.24,
      p=0.001). The number of cases with the highest possible score was 24 (20%) for
      the KSKS and 47 (39%) for the KSFS, whereas none of the cases obtained the
      highest possible KKS. According to the standard deviation method, more
      substantial ceiling effects were present in the KSKS (83 cases, 69.1%) and KSFS
      (67 cases, 55.8%) than in the KKS (23 cases, 19.2%). CONCLUSIONS: Although, the
      KKS was effective in reducing the ceiling effect, it demonstrated limited
      improvement in assessing the ability to perform high knee flexion after TKA.
      However, the 'floor life' subdomain of KSS appeared to be valid for evaluating
      high flexion of the knee.

PMID- 25750890
TI  - Results of gender-specific total knee arthroplasty: comparative study with
      traditional implant in female patients.
AB  - PURPOSE: To compare the incidence of overhang between two distinct femoral
      components and whether there is clinical and radiological benefit of gender
      specific implants in short-term follow-up. MATERIALS AND METHODS: One hundred and
      four knees in consecutive 66 female patients who underwent primary total knee
      arthroplasty due to primary osteoarthritis were included in this study. Overhang
      was measured and recorded in every cut surface of femur with both gender-specific
      and traditional trial femoral components respectively in every patient. Then, the
      knees were divided into two groups according to the type of the permanent femoral
      component they received. Clinical and radiological outcomes were compared between
      2 groups at minimum 3 years after operation. RESULTS: Mean follow-up duration was
      41.3 months (range, 36 to 50 months). Sixty two knees (59.6%) showed femoral
      overhang at least in one area with a traditional trial component, while 26 knees
      (25.0%) did with a gender-specific trial component (p<0.001). In terms of range
      of motion, Hospital for Special Surgery knee score, radiographic result, patella
      tilt angle and displacement, no significant difference was observed between two
      groups. CONCLUSIONS: The use of gender-specific implants substantially reduced
      the incidence of femoral overhang but did not demonstrate any clinical,
      functional or radiologic benefit in short-term follow-up.

PMID- 25750891
TI  - Patients still wish for key improvements after total knee arthroplasty.
AB  - PURPOSE: Our goals were to rigorously document and explore the interrelationships
      of various parameters in the aftermath of total knee arthroplasty (TKA),
      including patient characteristics, clinical scores, satisfaction levels, and
      patient-perceived improvements. MATERIALS AND METHODS: A questionnaire addressing
      sociodemographic factors, levels of satisfaction, and "wished-for" improvements
      was administered to 180 patients at least 1 year post primary TKA. Both
      satisfaction levels and wished-for improvements were assessed through nine paired
      parameters. Patients responded using an 11-point visual analogue scale (VAS) and
      the results were summarized as mean VAS score. Correlations between clinical
      scores and satisfaction levels and between satisfaction levels and desired
      improvements were analyzed. RESULTS: Patient satisfaction levels were only modest
      (mean score, 4-7) for eight of the nine parameters, including pain relief and
      restoration of daily living activities, the top two ranked parameters in wished
      for improvement while high-flexion activity constituted the top source of
      discontent. Wished-for improvement was high in seven parameters, the top three
      being restoration of daily living activities, pain relief, and high-flexion
      activity. The effects of sociodemographic factors on satisfaction levels and
      wished-for improvement varied. Satisfaction levels correlated positively with
      functional outcomes, and satisfaction in pain relief and restoration of daily
      living activities correlated more often and most strongly with clinical scores.
      CONCLUSIONS: Following TKA, patient satisfaction is not high for a number of
      issues, with improvements clearly needed in restoring daily living activities and
      relieving pain. Continued efforts to achieve better surgical outcomes should
      address patient-perceived shortcomings.

PMID- 25750892
TI  - Anatomic Double-Bundle Anterior Cruciate Ligament Reconstruction Using an Outside
      in Technique: Two- to Six-Year Clinical and Radiological Follow-up.
AB  - PURPOSE: We evaluated the clinical and radiological outcomes of double-bundle
      anterior cruciate ligament (ACL) reconstruction using an outside-in technique
      with a follow-up of two- to six-years, especially in terms of the sports activity
      level and radiological degeneration. MATERIALS AND METHODS: Sixty-seven patients
      who were available for a minimum two-year follow-up after double-bundle ACL
      reconstruction using an outside-in technique were retrospectively evaluated. The
      mean follow-up period was 43.7 months. The knee function and stability were
      evaluated before the operation, one year after the operation (short-term follow
      up), and more than two years after the operation (last follow-up). RESULTS:
      Regarding the knee function, the Lysholm score, International Knee Documentation
      Committee (IKDC) evaluation, and hop test showed significant improvement.
      Regarding the stability, the Lachman test, pivot shift test, KT-2000 arthrometer
      data, and anterior drawer radiographs using Telos showed significant improvement.
      Regarding the sports activity level, the patients who returned to pre-injury
      level activity was 68.7% according to the Tegner activity score and 76.1%
      according to the Cincinnati sports activity scale score. The incidence of
      aggravated degeneration or development of greater than IKDC grade A degeneration
      after surgery was 10.4%. CONCLUSIONS: Double-bundle ACL reconstruction using an
      outside-in technique showed favorable clinical and radiological outcomes with
      respect to the knee function and stability, joint degeneraion, and, especially,
      return to pre-injury sports activity.

PMID- 25750893
TI  - Single-Bundle Anterior Cruciate Ligament Reconstruction with Semitendinosus
      Tendon Using the PINN-ACL CrossPin System: Minimum 4-Year Follow-up.
AB  - PURPOSE: This study evaluated mid-term results of anterior cruciate ligament
      (ACL) reconstruction using the PINN-ACL CrossPin system that allowed for short
      graft fixation. MATERIALS AND METHODS: Forty-three patients underwent single
      bundle ACL reconstruction with a 4-strand semitendinosus tendon graft using the
      PINN-ACL CrossPin system. Femoral fixation was done using the PINN-ACL CrossPin
      system, and the tibial side was fixed with post-tie and a bioabsorbable
      interference screw. The mean follow-up period was 50 months. Evaluation was done
      using the Lachman test, pivot-shift test, International Knee Documentation
      Committee (IKDC) score and grade. Anterior displacement was assessed. RESULTS:
      There was improvement in the Lachman test and pivot-shift test at final follow
      up, form grade II (n=40) or III (n=3) to grade I (n=3) or 0 (n=40) and from grade
      I (n=20) or II (n=10) to grade I (n=8) or 0 (n=22), respectively. The mean IKDC
      score was 88.7, and grade A and B were 93.0% at final follow-up. Side-to-side
      difference was improved from 6.7 mm to 2.1 mm at final follow-up. Complications
      occurred in 3 patients, a re-ruptured due to trauma at 2 years after surgery and
      a deep infection and a superficial infection. CONCLUSIONS: The mid-term follow-up
      results of ACL reconstruction with the PINN-ACL CrossPin system were
      satisfactory. The PINN-ACL CrossPin can be considered as a useful instrument for
      short graft fixation.

PMID- 25750894
TI  - Coronal alignment of the lower limb and the incidence of constitutional varus
      knee in korean females.
AB  - PURPOSE: In total knee arthroplasty (TKA), it is important to restore neutral
      mechanical alignment. The purpose of this study was to assess whether the lower
      limb alignment is neutral in healthy Korean females and investigate the incidence
      of constitutional varus knees among them. MATERIALS AND METHODS: Weight-bearing
      full-leg standing radiographs were obtained from 118 healthy females between the
      ages of 20 to 39 years. One radiologist and two orthopaedic surgeons measured the
      hip-knee-ankle angle (HKAA), medial proximal tibial angle (MPTA), and femoral
      anatomic mechanical angle (FAMA) on the radiographs and compared with the
      traditional gold standard HKAA of 0 degrees , MPTA of 3 degrees  varus, and FAMA
      of 6 degrees . RESULTS: The interobserver reliability of the three independent
      observers was high (p<0.001). The HKAA of the study subjects (1.35 degrees +/
      2.04 degrees ) was significantly different from the standard HKAA of 0 degrees 
      (p<0.001), but no statistically significant difference was observed in the MPTA (
      3.18 degrees +/-1.61 degrees ) and FAMA (5.99 degrees +/-0.70 degrees ) from the
      standard values (p=0.083 and p=0.887, respectively). The incidence of
      constitutional varus alignment was 20.34%. CONCLUSIONS: In Korean females, the
      mechanical axis of the lower limb was not neutral and the incidence of
      constitutional varus alignment was slightly higher than that in Western females.
      We believe that these findings should be taken into consideration in planning
      reconstructive surgery of the knee, such as TKA, unicompartmental knee
      arthroplasty, and high tibial osteotomy.

PMID- 25750895
TI  - The FasT-Fix Repair Technique for Ramp Lesion of the Medial Meniscus.
AB  - INTRODUCTION: This technical note describes a new arthroscopic technique to
      repair the peripheral attachment lesion of the posterior horn of the medial
      meniscus. The operation was performed under arthroscopy using a standard anterior
      portal. SURGICAL TECHNIQUE: A FasT-Fix needle was inserted obliquely close to the
      tibial plateau and the first implant was inserted into the joint capsule
      depending on its bending angle underneath the meniscus. The second implant was
      inserted through 1/3 periphery of the meniscus into the meniscocapsular area. The
      pre-tied self-sliding knot was tensioned to achieve secure fixation of the
      posterior meniscal peripheral attachment at the original attachment point.
      MATERIALS AND METHODS: From August 2011 to February 2014, 23 knees were diagnosed
      as ramp lesion, underwent meniscal repair using FasT-Fix technique. RESULTS: All
      patients were followed up for average 14 months. The Lysholm score improved from
      preoperative 64.4+/-4.52 to postoperative 91.2+/-4.60. CONCLUSIONS: We believe
      that the FasT-Fix technique via the standard anterior portal can be a more
      convenient and less traumatic alternative for repair of the peripheral attachment
      lesion of the posterior horn of the medial meniscus in the anterior cruciate
      ligament deficient knee.

PMID- 25750896
TI  - Arthroscopic burring of exposed cement following curettage and cavity filling
      cementation for chondroblastoma of the proximal tibia.
AB  - Chondroblastoma of the proximal tibia is difficult to treat because of its
      epiphyseal predilection. This condition can be treated by curettage, which
      results in immediate restoration of stability and a reduced recurrence rate,
      followed by cement filling of the bone defect. Nevertheless, contact with cement
      can damage articular cartilage, potentially leading to severe knee
      osteoarthritis. Most previous reports regarding this complication described
      patients with giant cell tumors of the proximal tibia. We present here a patient
      who underwent arthroscopic treatment for cement exposure caused by articular
      cartilage loss of the tibial plateau, which occurred after initial curettage and
      cementation for chondroblastoma of the proximal tibia. To our knowledge, this is
      the first report on arthroscopic treatment of this condition. 

PMID- 25750897
TI  - Spontaneous healing of a displaced bucket-handle tear of the lateral meniscus in
      a child.
AB  - Bucket-handle tears less frequently occur in the lateral meniscus than in the
      medial meniscus. An 11-year-old male patient complained of painful swelling and
      locking due to a displaced bucket-handle tear of the lateral meniscus. We
      recommended an arthroscopic surgery; however, the patient left the hospital
      without surgical treatment. Six weeks afterwards, he returned without any
      complain of pain and he regained full range of motion. The final follow-up
      magnetic resonance imaging showed reduction of the torn meniscal fragment without
      any signal changes suggestive of a meniscal tear. We report a rare case of an
      isolated displaced bucket-handle tear of the lateral meniscus in an 11-year-old
      patient that healed spontaneously without surgical intervention. 

PMID- 25750898
TI  - The ever-expanding immunomodulatory role of calreticulin in cancer immunity.
AB  - Calreticulin is a pleiotropic molecule that normally resides in the lumen of the
      endoplasmic reticulum (ER). Here, it has various functions, ranging from
      regulation of calcium homeostasis to ensuring proper protein folding. More
      recently, calreticulin gained special interest for its extracellular functions,
      where it has direct immunomodulatory activity. In this respect, calreticulin
      activates dendritic cells and macrophages. In addition, certain anti-cancer
      therapies induce the translocation of calreticulin from the ER to the cell
      surface of dying cancer cells, where calreticulin dictates the immunogenicity of
      these cells. Interestingly, treatment with tumor necrosis factor (TNF)-related
      apoptosis inducing ligand (TRAIL) also induces membrane calreticulin exposure on
      cancer cells. As shown here, calreticulin directly interacts with TRAIL and its
      receptor-signaling complex, as well as with other TNF family members. Of note,
      TRAIL is a well known immunomodulatory molecule, and is expressed on the surface
      of natural killer T-cells. Therefore, calreticulin may have an as yet
      unrecognized wide(r) impact on immunity, with the TNF-ligand family modulating
      virtually all aspects of the immune response. 

PMID- 25750900
TI  - Supportive and rejective functions of tumor stroma on tumor cell growth,
      survival, and invasivity: the cancer evolution.

PMID- 25750902
TI  - Editorial.

PMID- 25750899
TI  - The Interplay between PP2A and microRNAs in Leukemia.
AB  - Protein phosphatase 2A (PP2A) is a serine/threonine phosphatase family whose
      members have been implicated in tumor suppression in many cancer models. In many
      cancers, loss of PP2A activity has been associated with tumorigenesis and drug
      resistance. Loss of PP2A results in failure to turn off survival signaling
      cascades that drive drug resistance such as those regulated by protein kinase B.
      PP2A is responsible for modulating function and controlling expression of tumor
      suppressors such as p53 and oncogenes such as BCL2 and MYC. Thus, PP2A has
      diverse functions regulating cell survival. The importance of microRNAs (miRs) is
      emerging in cancer biology. A role for miR regulation of PP2A is not well
      understood; however, recent studies suggest a number of clinically significant
      miRs such as miR-155 and miR-19 may include PP2A targets. We have recently found
      that a PP2A B subunit (B55alpha) can regulate a number of miRs in acute myeloid
      leukemia cells. The identification of a miR/PP2A axis represents a novel
      regulatory pathway in cellular homeostasis. The ability of miRs to suppress
      specific PP2A targets and for PP2A to control such miRs can add an extra level of
      control in signaling that could be used as a rheostat for many signaling cascades
      that maintain cellular homeostasis. As such, loss of PP2A or expression of miRs
      relevant for PP2A function could promote tumorigenesis or at least result in drug
      resistance. In this review, we will cover the current state of miR regulation of
      PP2A with a focus on leukemia. We will also briefly discuss what is known of PP2A
      regulation of miR expression. 

PMID- 25750901
TI  - Management of erectile dysfunction post-radical prostatectomy.
AB  - Radical prostatectomy is a commonly performed procedure for the treatment of
      localized prostate cancer. One of the long-term complications is erectile
      dysfunction. There is little consensus on the optimal management; however, it is
      agreed that treatment must be prompt to prevent fibrosis and increase oxygenation
      of penile tissue. It is vital that patient expectations are discussed, a
      realistic time frame of treatment provided, and treatment started as close to the
      prostatectomy as possible. Current treatment regimens rely on phosphodiesterase 5
      inhibitors as a first-line therapy, with vacuum erection devices and
      intraurethral suppositories of alprostadil as possible treatment combination
      options. With nonresponders to these therapies, intracavernosal injections are
      resorted to. As a final measure, patients undergo the highly invasive penile
      prosthesis implantation. There is no uniform, objective treatment program for
      erectile dysfunction post-radical prostatectomy. Management plans are based on
      poorly conducted and often underpowered studies in combination with physician and
      patient preferences. They involve the aforementioned drugs and treatment methods
      in different sequences and doses. Prospective treatments include dietary
      supplements and gene therapy, which have shown promise with there proposed
      mechanisms of improving erectile function but are yet to be applied successfully
      in human patients. 

PMID- 25750903
TI  - Trapeziometacarpal osteoarthritis: pyrocarbon interposition implants.
AB  - PURPOSE: the aim of this study was to evaluate the effectiveness of interposition
      arthroplasty of the trapeziometacarpal (TMC) joint with pyrolitic carbon implants
      for the treatment of TMC osteoarthritis. METHODS: we evaluated two groups of
      patients surgically treated for TMC osteoarthritis: group 1 (34 patients - 36 TMC
      joints) treated with PyroDisk implantation and group 2 (25 patients - 25 TMC
      joints) treated with the Pyrocardan implant. All these patients were clinically
      evaluated at follow-up using the DASH score, Mayo Wrist score and VAS pain score.
      RESULTS: the mean follow-up was 42 months in group 1 and 12 months in group 2.
      Both groups showed good clinical outcomes in terms of pain relief, range of
      motion, and pinch and grasp strength. Revision surgery was needed in only one
      case in group 1 (2.8%) and in three cases (12%) in group 2. CONCLUSIONS:
      prosthetic replacement of the TMC joint was found to be a good solution for low
      demand patients. However, the PyroDisk could be a good solution in selected
      patients (Eaton stage I-III, non-subluxated joint): it provides good pain relief,
      good range of motion, good pinch and grasp strength, and stable results at more
      than three-years of follow-up. LEVEL OF EVIDENCE: Level IV, therapeutic case
      series.

PMID- 25750904
TI  - In vitro characterization of stem/progenitor cells from semitendinosus and
      gracilis tendons as a possible new tool for cell-based therapy for tendon
      disorders.
AB  - PURPOSE: this study was conducted to characterize tendon stem/progenitor cells
      (TSPCs) isolated from human semitendinosus and gracilis tendons in terms of
      stemness properties and multi-differentiation potential. METHODS: TSPCs were
      isolated from waste portions of semitendinosus and gracilis tendons from three
      donors who underwent anterior cruciate ligament reconstruction. TSPCs were plated
      in culture until passage 4, when experiments to assess cell proliferation,
      viability and clonogenic ability were performed. The immunophenotype of TSPCs was
      evaluated by cytofluorimetric analysis. The in vitro osteogenic, chondrogenic,
      adipogenic and tenogenic potential was evaluated using biochemical, histological
      and gene expression analysis to detect specific differentiation markers.
      Statistical analysis was performed using Student's t-test. RESULTS: after a few
      passages in culture the cell populations showed a homogeneous fibroblast-like
      morphology typical of mesenchymal stem cells. The average doubling time of TSPCs
      increased from 52.4+/-4.8 at passage 2 to 100.8+/-23.4 hours at passage 4. The
      highest percentage of colonies was also found at passage 4 (4.7+/-2.3%). TSPCs
      showed the typical mesenchymal phenotype, with high expression of CD73, CD90 and
      CD105 and no expression of CD34 and CD45. Cells induced to differentiate toward
      osteogenic lineage showed significant upregulations of ALP activity (+189%,
      p<0.05) and calcified matrix deposition (+49%, p<0.05) compared with
      undifferentiated cells; culture in chondrogenic medium also provoked a
      significant increase in glycosaminoglycan levels (+108%, p<0.05). On the other
      hand, TSPCs were not able to respond to adipogenic stimuli. Scleraxis gene
      expression and decorin gene expression, considered tenogenic markers, were
      already very high in control cells, and culture in tenogenic medium further
      increased these values although not significantly. CONCLUSIONS: our data show
      that it is possible to isolate TSPCs from very small fragments of tissue and that
      they show the typical features of MSCs and multi-differentiation potential, above
      all toward osteogenic and chondrogenic lineages. CLINICAL RELEVANCE: this study
      can be considered one of the first attempts to clarify the biology of tendon cell
      populations, focusing in particular on the potential applicability of this cell
      source for future regenerative medicine purposes.

PMID- 25750905
TI  - Periprosthetic joint infections: a clinical practice algorithm.
AB  - PURPOSE: periprosthetic joint infection (PJI) accounts for 25% of failed total
      knee arthroplasties (TKAs) and 15% of failed total hip arthroplasties (THAs). The
      purpose of the present study was to design a multidisciplinary diagnostic
      algorithm to detect a PJI as cause of a painful TKA or THA. METHODS: from April
      2010 to October 2012, 111 patients with suspected PJI were evaluated. The study
      group comprised 75 females and 36 males with an average age of 71 years (range,
      48 to 94 years). Eighty-four patients had a painful THA, while 27 reported a
      painful TKA. The stepwise diagnostic algorithm, applied in all the patients,
      included: measurement of serum C-reactive protein (CRP) and erythrocyte
      sedimentation rate (ESR) levels; imaging studies, including standard radiological
      examination, standard technetium-99m-methylene diphosphonate (MDP) bone scan (if
      positive, confirmation by LeukoScan was obtained); and joint aspiration with
      analysis of synovial fluid. RESULTS: following application of the stepwise
      diagnostic algorithm, 24 out of our 111 screened patients were classified as
      having a suspected PJI (21.7%). CRP and ESR levels were negative in 84 and
      positive in 17 cases; 93.7% of the patients had a positive technetium-labeled
      bone scan, and 23% a positive LeukoScan. Preoperative synovial fluid analysis was
      positive in 13.5%; analysis of synovial fluid obtained by preoperative aspiration
      showed a leucocyte count of > 3000 cells MU/l in 52% of the patients.
      CONCLUSIONS: the present study showed that the diagnosis of PJI requires the
      application of a multimodal diagnostic protocol in order to avoid complications
      related to surgical revision of a misdiagnosed "silent" PJI. LEVEL OF EVIDENCE:
      Level IV, therapeutic case series.

PMID- 25750906
TI  - Surgical treatment of partial anterior cruciate ligament lesions: medium-term
      results.
AB  - PURPOSE: this study was conducted to evaluate subjective and objective clinical
      outcomes of partial reconstruction of the anterior cruciate ligament (ACL) in
      comparison with complete ACL reconstruction. METHODS: three groups, each
      comprising 20 patients, were evaluated at a minimum follow-up of 12 months. The
      group 1 patients underwent partial ACL reconstruction, while those in group 2 and
      group 3 underwent complete ACL reconstruction, performed using either bone
      patellar tendon-bone (BPTB) or quadrupled hamstring tendon (HT) grafts,
      respectively. The subjective outcome was evaluated using the Lysholm knee scale
      and the subjective International Knee Documentation Committee (IKDC) scoring
      system. A visual analog scale (VAS) was used for pain assessment and sporting
      activity was rated using the Tegner activity scale. Objective evaluation was
      performed using the IKDC objective form, KT-1000 arthrometer and KiRA triaxial
      accelerometer. RESULTS: at the follow-up evaluation, the mean subjective IKDC
      score was 86.1+/-10.3 in group 1, 85.2+/-11.1 in group 2, and 82.7+/-7.8 in group
      3. The Lysholm score was 91.3+/-7.3 in group 1, 91.7+/-9.6 in group 2, and 89.4+/
      6.1 in group 3. KT-1000 tests showed a mean side-to-side difference of 1.1 mm +/-
      1.5 mm (range, 0-5 mm) in group 1; 0.79 mm +/- 0.8 mm (range, 0-2mm) in group 2;
      and 1.45 mm +/- 1 mm (range, 0-3 mm) in group 3. The differences between groups
      were not statistically significant. CONCLUSIONS: both subjective and objective
      outcomes of partial ACL reconstruction were comparable to those of complete
      reconstruction, but partial reconstruction in the presence of a partial lesion of
      the ACL is considered by the authors to be more respectful of the native
      vascularization, innervation and anatomy of the ACL, conferring an advantage in
      terms of recovery of the complete function of the knee. LEVEL OF EVIDENCE: Level
      III, retrospective comparative study.

PMID- 25750907
TI  - Sports-related changes of the synovial membrane.
AB  - PURPOSE: the aim of this study is to differentiate the behavior of the synovial
      membrane in the presence of various stimuli in patients who practice sports.
      METHODS: fifty one patients (30 males and 21 females, mean age 48 years, range 31
      59 years) who actively practiced non-competitive sports underwent a biopsy of the
      synovial membrane during arthroscopic surgery performed for joint effusion
      secondary to meniscal lesion (24 cases), anterior cruciate ligament injury (ACL)
      (17 cases), postoperative knee joint stiffness (2 cases), aseptic loosening or
      dislocation of the polyethylene component of uni-compartmental knee arthroplasty
      (5 cases), and anterior fibrous impingement of the ankle (3 cases). Synovial
      tissue samples were obtained during surgery from all the patients and processed
      for light microscopy, transmission electron microscopy and scanning electron
      microscopy observation. RESULTS: circulatory phenomena were observed in acute
      inflammatory processes, characterized by hyperemia and vasodilation. Exudative
      and infiltrative phenomena were observed in the presence of foreign bodies and
      were characterized by leukocytic exudation (presence of polynuclear neutrophils),
      accompanied by lymphomonocytic infiltration. Proliferative phenomena were
      observed in post-traumatic forms of synovitis (ACL and meniscal injuries),
      characterized by hypertrophy and proliferation of villous formations.
      Degenerative and regressive phenomena were observed in cases of fibrous reaction
      (ankle impingement and joint stiffness) and were characterized by formation of
      dense fibrous connective tissue with hyaline patches, evolving towards sclerosis.
      CONCLUSIONS: the activation of inflammatory processes in patients who expose
      their joints to excessive stress may lead to the formation of hyperplastic
      tissue. Ultramicroscopic debris is usually capable of transforming the structural
      organization of the synovial tissue. LEVEL OF EVIDENCE: Level IV, observational
      case series.

PMID- 25750908
TI  - Treatment of juvenile osteochondritis dissecans of the talus: current concepts
      review.
AB  - Juvenile osteochondritis dissecans of the talus (JODT) affects the subchondral
      bone primarily and, in a skeletally immature population, articular cartilage
      secondarily. It probably consists of aseptic bone necrosis whose spontaneous
      healing is impaired by microtraumas, resulting in an osteochondral injury and, in
      some cases, in osteoarthritis. In many cases the clinical presentation is
      asymptomatic. Mild chronic pain is frequent, sometimes accompanied by swelling,
      stiffness or locking. Few data are currently available on this topic and,
      moreover, most existing data were obtained from mixed groups and populations; it
      is therefore difficult to outline a scheme for the treatment of JODT. However,
      the most suitable treatment in the first stages of the disease is conservative.
      The presence of a loose body is an indication for surgical fixation, drilling or
      regenerative procedures, depending on the presence/extent of subchondral bone
      sclerosis and the surgeon's experience. Drilling has been shown to promote the
      healing of lesions with minimal surgical trauma. Microfractures, since they
      induce fibrocartilage repair, are to be considered only for small injuries.
      Mosaicplasty and osteochondral autograft transplantation may cause donor site
      morbidity and are techniques little reported in JODT. Regenerative techniques and
      fresh allografts give good results in osteochondral lesions, but further studies
      are required to describe the results that can be obtained in JODT alone. 

PMID- 25750910
TI  - Effect on bone formation of the autogenous tooth graft in the treatment of peri
      implant vertical bone defects in the minipigs.
AB  - BACKGROUND: The aim of this study was to evaluate the effect of autogenous tooth
      bone as a graft material for regeneration of bone in vertical bony defects of the
      minipigs. MATERIAL AND METHODS: Six minipigs were used in this study. Four molars
      were extracted in the right mandibular dentition and sent to the Korea Tooth Bank
      for fabrication of autogenous tooth bone. Ten days later, each extraction site
      was implanted with MS Implant Narrow Ridge 3.0x10mm fixture (Osstem, Seoul,
      Korea) after standardized 2mm-sized artificial vertical bony defect formation.
      Pineappleshaped Root-On type autogenous tooth bones were applied to the vertical
      defects around the neck area of the posterior three fixtures and the fore-most
      one was not applied with autogenous bone as a control group. Each minipig was
      sacrificed at 4, 8, 12 weeks after fixture installation and examined
      radiologically and histologically. Histological evaluation was done under light
      microscope with Villanueva osteochrome bone staining with semi-quantitative
      histomorphometric study. Percentage of new bone over total area (NBF) and bone to
      implant contact (BIC) ratio were evaluated using digital software for area
      calculation. RESULT: NBF were 48.15 +/- 18.02%, 45.50 +/- 28.37%, and 77.13 +/-
      15.30% in 4, 8, and 12 weeks, respectively for experimental groups. The control
      group showed 37.00 +/- 11.53%, 32.25 +/- 26.99%, and 1.33 +/- 2.31% in 4,8,12
      weeks, respectively. BIC ratio were 53.08 +/- 19.82%, 45.00 +/- 28.37%, and 75.13
      +/- 16.55% in 4,8,12 weeks, respectively. Those for the control groups were 38.33
      +/- 6.43%, 33.50 +/- 29.51 %, and 1.33 +/- 2.31% in 4, 8, 12 weeks, respectively.
      CONCLUSION: Autogenous tooth bone showed higher score than control group in NBF
      and BIC in all the data encompassing 4,8,12 weeks specimens, but statistically
      significant only 12 weeks data in both NBF and BIC.

PMID- 25750909
TI  - Meniscal injuries in basketball players.
AB  - Basketball is a highly competitive sport in which the knee joint is constantly
      subject to physical stresses. Basketball-related traumatic injuries are the
      result of specific technical movements. Even though basketball is not considered
      a contact sport, injuries in basketball players are due both to athletes'
      handling of the ball and to their intense physical interaction during games.
      Nowadays, traumatic meniscal injuries are constantly on the increase, especially
      in young athletes, and they are generally the result of compressive forces
      together with knee flexion rotation. Recognition of the great importance of
      meniscal biomechanics and of the functional role of the meniscus has resulted in
      the adoption of an increasingly preserving approach, also in the light of the
      effects, in terms of articular degeneration, of removing meniscal tissue. Even
      though recent decades have seen considerable developments in arthroscopic
      meniscectomy techniques, geared at preserving as much meniscal tissue as
      possible, basketball players undergoing this treatment often present, in the long
      run, clinical symptomatology severe enough to compromise their participation in
      competitive sport. Hence the treatment of meniscal injuries in athletes has
      become more and more preserving in recent years, through recourse to surgical
      techniques such as meniscal repair, biological replacement implantation and donor
      meniscus implantation, which allow pain relief, return to competitive activities
      and stable long-term results, slowing down arthritic progression. Therefore,
      considering the increasing number of meniscal injuries in basketball players,
      which can jeopardize their sporting careers, great importance is now attached to
      early diagnosis and to the correct choice of meniscal injury treatment in these
      athletes. 

PMID- 25750911
TI  - Protein S-nitrosylation: specificity and identification strategies in plants.
AB  - The role of nitric oxide (NO) as a major regulator of plant physiological
      functions has become increasingly evident. To further improve our understanding
      of its role, within the last few years plant biologists have begun to embrace the
      exciting opportunity of investigating protein S-nitrosylation, a major reversible
      NO-dependent post-translational modification (PTM) targeting specific Cys
      residues and widely studied in animals. Thanks to the development of dedicated
      proteomic approaches, in particular the use of the biotin switch technique (BST)
      combined with mass spectrometry, hundreds of plant protein candidates for S
      nitrosylation have been identified. Functional studies focused on specific
      proteins provided preliminary comprehensive views of how this PTM impacts the
      structure and function of proteins and, more generally, of how NO might regulate
      biological plant processes. The aim of this review is to detail the basic
      principle of protein S-nitrosylation, to provide information on the biochemical
      and structural features of the S-nitrosylation sites and to describe the
      proteomic strategies adopted to investigate this PTM in plants. Limits of the
      current approaches and tomorrow's challenges are also discussed. 

PMID- 25750912
TI  - CK1delta in lymphoma: gene expression and mutation analyses and validation of
      CK1delta kinase activity for therapeutic application.
AB  - The prognosis of lymphoid neoplasms has improved considerably during the last
      decades. However, treatment response for some lymphoid neoplasms is still poor,
      indicating the need for new therapeutic approaches. One promising new strategy is
      the inhibition of kinases regulating key signal transduction pathways, which are
      of central importance in tumorigenesis. Kinases of the CK1 family may represent
      an attractive drug target since CK1 expression and/or activity are associated
      with the pathogenesis of malignant diseases. Over the last years efforts were
      taken to develop highly potent and selective CK1-specific inhibitor compounds and
      their therapeutic potential has now to be proved in pre-clinical trials.
      Therefore, we analyzed expression and mutational status of CK1delta in several
      cell lines representing established lymphoma entities, and also measured the mRNA
      expression level in primary lymphoma tissue as well as in non-neoplastic blood
      cells. For a selection of lymphoma cell lines we furthermore determined CK1delta
      kinase activity and demonstrated therapeutic potential of CK1-specific inhibitors
      as a putative therapeutic option in the treatment of lymphoid neoplasms. 

PMID- 25750913
TI  - Multi-omics analysis identifies genes mediating the extension of cell walls in
      the Arabidopsis thaliana root elongation zone.
AB  - Plant cell wall composition is important for regulating growth rates, especially
      in roots. However, neither analyses of cell wall composition nor transcriptomes
      on their own can comprehensively reveal which genes and processes are mediating
      growth and cell elongation rates. This study reveals the benefits of carrying out
      multiple analyses in combination. Sections of roots from five anatomically and
      functionally defined zones in Arabidopsis thaliana were prepared and divided into
      three biological replicates. We used glycan microarrays and antibodies to
      identify the major classes of glycans and glycoproteins present in the cell walls
      of these sections, and identified the expected decrease in pectin and increase in
      xylan from the meristematic zone (MS), through the rapid and late elongation
      zones (REZ, LEZ) to the maturation zone and the rest of the root, including the
      emerging lateral roots. Other compositional changes included extensin and
      xyloglucan levels peaking in the REZ and increasing levels of arabinogalactan
      proteins (AGP) epitopes from the MS to the LEZ, which remained high through the
      subsequent mature zones. Immuno-staining using the same antibodies identified the
      tissue and (sub)cellular localization of many epitopes. Extensins were localized
      in epidermal and cortex cell walls, while AGP glycans were specific to different
      tissues from root-hair cells to the stele. The transcriptome analysis found
      several gene families peaking in the REZ. These included a large family of
      peroxidases (which produce the reactive oxygen species (ROS) needed for cell
      expansion), and three xyloglucan endo-transglycosylase/hydrolase genes (XTH17,
      XTH18, and XTH19). The significance of the latter may be related to a role in
      breaking and re-joining xyloglucan cross-bridges between cellulose microfibrils,
      a process which is required for wall expansion. Knockdowns of these XTHs resulted
      in shorter root lengths, confirming a role of the corresponding proteins in root
      extension growth. 

PMID- 25750914
TI  - MOLECULAR MODELLING, 3D-QSAR, AND DRUG DOCKING STUDIES ON THE ROLE OF NATURAL
      ANTICOAGULANT COMPOUNDS IN ANTITHROMBOTIC THERAPY.
AB  - Thromboembolic disorders are the leading cause of human mortality. Therefore,
      development of effective anticoagulant therapy is critical. Factor XIIIA (FXIIIA)
      protein is a crucial factor in the blood coagulation cascade, and hence it is a
      vital target for evolution of new antithrombotic agents. Structure-function
      studies of clotting factor active sites, clot formation, and thrombus structure
      have gained prominence in the efforts to develop novel anticoagulants. Factor
      XIIIA was homology modelled with the human transglutaminase-2 crystal structure
      as a base template for BLAST analysis. Docking and comparative binding site
      analysis revealed active site residue conservation and inhibitor-protein
      interactions. Nineteen small molecules possessing suspected anticoagulant
      properties were successfully docked into the FXIIIA active site following the
      best CoMFA and CoMSIA prediction values. Dabigatran etexilate was anticipated to
      be the best FXIIIA inhibitor among the nineteen anticoagulants with the highest
      binding affinity for the FXIIIA protein and the highest FlexX dock score of -29.8
      KJ/mol. Structural properties of FXIIIA inhibitors with increased antithrombotic
      activity were predicted by this docking study.

PMID- 25750915
TI  - Priming of Early Closure: Evidence for the Lexical Boost during Sentence
      Comprehension.
AB  - Two self-paced reading experiments investigated priming in sentences containing
      "early" vs. "late closure" ambiguities. Early closure sentences impose relatively
      large processing costs at the point of syntactic disambiguation (Frazier &
      Rayner, 1982). The current study investigated a possible way to reduce processing
      costs. Target sentences were temporarily ambiguous and were disambiguated towards
      either the preferred "late" closure analysis or the dispreferred "early" closure
      analysis. Each target sentence was preceded by a prime that was either
      structurally identical or that required a different syntactic analysis. In
      Experiment 1, all of the prime sentences shared the same critical verb as the
      target (Arai et al., 2007; Carminati et al., 2008; Tooley et al., 2009, in press;
      Traxler et al., in press; Weber & Indefrey, 2009). In Experiment 2, verb
      repetition was eliminated by reorganizing the stimuli from Experiment 1. In
      Experiment 1, processing of the disambiguating verb was facilitated when an
      "early" closure target sentence followed an "early" closure prime. In Experiment
      2, there were no significant priming effects, although an overall difference in
      processing time favored "late closure" targets. Combined analyses verified that
      the pattern of results in Experiment 1 differed significantly from Experiment 2.
      These experiments provide the first indication that "early" closure analyses can
      be primed and that such priming is more robust when a critical verb appears in
      both the prime and the target sentence. The results add to the body of data
      indicating a "lexical boost" for syntactic priming effects during comprehension.
      They have implications for theories of syntactic representation and processing
      (e.g., Boland & Blodgett, 2006; Vosse & Kempen, 2009; Sag et al., 2003).

PMID- 25750916
TI  - Efficacy of delayed-release dimethyl fumarate in relapsing-remitting multiple
      sclerosis: integrated analysis of the phase 3 trials.
AB  - OBJECTIVE: Obtain a more precise estimate of the efficacy of delayed-release
      dimethyl fumarate (DMF; also known as gastro-resistant DMF) in relapsing multiple
      sclerosis (MS) and examine the consistency of DMF's effects across patient
      subgroups stratified by baseline demographic and disease characteristics.
      METHODS: A prespecified integrated analysis of the randomized, double-blind,
      placebo-controlled, Phase 3 DEFINE and CONFIRM trials was conducted. RESULTS: The
      intent-to-treat population comprised 2301 patients randomized to receive placebo
      (n = 771) or DMF 240 mg twice daily (BID; n = 769) or three times daily (TID; n =
      761). At 2 years, DMF BID and TID reduced the annualized relapse rate by 49% and
      49% (both P < 0.0001), risk of relapse by 43% and 47% (both P < 0.0001), risk of
      12-week confirmed disability progression by 32% (P = 0.0034) and 30% (P =
      0.0059), and risk of 24-week confirmed disability progression by 29% (P = 0.0278)
      and 32% (P = 0.0177), respectively, compared with placebo. In a subset of
      patients (MRI cohort), DMF BID and TID reduced the mean number of new/enlarging
      T2-hyperintense lesions by 78% and 73%, gadolinium-enhancing lesion activity by
      83% and 70%, and mean number of new nonenhancing T1-hypointense lesions by 65%
      and 64% (all P < 0.0001 vs. placebo). Effects were generally consistent across
      patient subgroups. INTERPRETATION: The integrated analysis provides a more
      precise estimate of DMF's efficacy. DMF demonstrated a robust reduction in
      disease activity and a consistent therapeutic effect across patient subgroups.

PMID- 25750917
TI  - Fingolimod treatment promotes regulatory phenotype and function of B cells.
AB  - OBJECTIVE: To evaluate the influence of Fingolimod treatment on B-cell subset
      composition and function in multiple sclerosis patients and its potential
      clinical relevance. METHODS: Subset composition and cytokine production of B
      cells derived from peripheral blood mononuclear cells from multiple sclerosis
      patients under Fingolimod treatment, untreated multiple sclerosis patients and
      healthy controls were analyzed by flow cytometry and ELISA. Migration of
      lymphocyte subsets across primary human brain microvascular endothelial cells was
      assessed in an in vitro transmigration assay. Cell numbers and composition of B
      cell subsets in cerebrospinal fluid and peripheral blood were determined by flow
      cytometry. Regulatory B-cell frequencies were correlated with parameters of
      disease stability. RESULTS: Within the peripheral B-cell compartment of
      Fingolimod-treated patients, the proportion of regulatory B cells (CD38(+)CD27(
      )CD24(+)CD5(+)) was significantly increased as compared to treatment-naive
      multiple sclerosis patients and to healthy controls, and significantly more
      regulatory B cells produced Interleukin-10. Fingolimod treatment enhanced the
      capacity of regulatory B cells to transmigrate across brain endothelial cells in
      an in vitro model of the blood-brain-barrier. In line with these findings, the
      cerebrospinal fluid/blood ratio of total B cells and regulatory B cells was
      strongly increased by Fingolimod treatment, and patients exhibited increased
      regulatory B-cell frequencies in the cerebrospinal fluid. Finally, elevated
      regulatory B-cell percentages in the periphery significantly correlated with
      clinical and paraclinical disease stability. INTERPRETATION: These data suggest a
      novel and as yet unrecognized role of Fingolimod in correction of the imbalance
      between regulatory and effector B-cell functions in multiple sclerosis both by
      direct effects and indirect partitioning effects on B-cell subpopulations.

PMID- 25750918
TI  - CSF beta-amyloid 1-42 - what are we measuring in Alzheimer's disease?
AB  - OBJECTIVE: To characterize biological and technical factors which influence
      cerebrospinal fluid (CSF) Alzheimer's disease (AD) biomarker levels, including
      the presence of apolipoprotein E (APOE) epsilon4 allele, AD diagnosis, Abeta
      binding proteins, sample processing, and preanalytical handling. METHODS: CSF was
      collected from 140 subjects with normal cognition, mild cognitive impairment, AD,
      and non-AD dementia. CSF levels of beta-amyloid 1-42 (Abeta42), total Tau (t
      Tau), and Tau phosphorylated at threonine 181 (p-Tau181) were analyzed following
      the standard and modified protocols. CSF levels of apoJ, apoE, albumin, and alpha
      synuclein were measured in a subgroup (n = 69), and their effects on measured AD
      biomarker levels were also determined in vitro using human CSF samples. RESULTS:
      CSF Abeta42 levels measured using the AD Neuro-imaging Initiative (ADNI) protocol
      (which we call suspended Abeta42 or susAbeta) were lower than total measurable
      CSF Abeta42 in all groups, and on average represents 57% of the latter. Logistic
      regression analysis showed this proportion (% susAbeta) to be directly correlated
      with CSF Abeta42 and apoJ levels, but inversely correlated with CSF t-Tau levels.
      Finally, we showed in vitro that increasing apoE and apoJ levels directly
      increased % susAbeta. CONCLUSION: CSF susAbeta levels are influenced by
      biological and technical factors, and may represent a marker of Abeta susceptible
      to lipoprotein-mediated clearance. Clinical trials should include total
      measurable Abeta42 and susAbeta to better inform outcomes.

PMID- 25750919
TI  - Visual pathway neurodegeneration winged by mitochondrial dysfunction.
AB  - OBJECTIVES: To test for structural and functional contribution of mitochondrial
      dysfunction to neurodegeneration in multiple sclerosis (MS). A visual pathway
      model void of MS lesions was chosen in order to exclude neurodegeneration
      secondary to lesion related axonotmesis. METHODS: A single-centre cohort study
      (230 MS patients, 63 controls). Spectral domain optical coherence tomography of
      the retina, 3T magnetic resonance imaging of the brain, spectrophotometric
      assessment of serum lactate levels. Postmortem immunohistochemistry. RESULTS: The
      visual pathway was void of MS lesions in 31 patients and 31 age-matched controls.
      Serum lactate was higher in MS compared to controls (P = 0.029). High serum
      lactate was structurally related to atrophy of the retinal nerve fiber layer at
      the optic disc (P = 0.041), macula (P = 0.025), and the macular ganglion cell
      complex (P = 0.041). High serum lactate was functionally related to poor color
      vision (P < 0.01), Expanded Disability Status Scale score (R = 0.37, P = 0.041),
      Guy's Neurological disability score (R = 0.38, P = 0.037), MS walking scale (R =
      0.50, P = 0.009), upper limb motor function (R = 0.53, P = 0.002).
      Immunohistochemistry demonstrated increased astrocytic expression of a key
      lactate generating enzyme in MS lesions as well as profound vascular expression
      of monocarboxylate transporter-1, which is involved in lactate transport.
      INTERPRETATION: This study provides structural, functional, and translational
      evidence for visual pathway neurodegeneration in MS related to mitochondrial
      dysfunction.

PMID- 25750920
TI  - Expression of FSHD-related DUX4-FL alters proteostasis and induces TDP-43
      aggregation.
AB  - OBJECTIVE: Pathogenesis in facioscapulohumeral muscular dystrophy (FSHD) appears
      to be due to aberrant expression, particularly in skeletal muscle nuclei, of the
      full-length isoform of DUX4 (DUX4-FL). Expression of DUX4-FL is known to alter
      gene expression and to be cytotoxic, but cell responses to DUX4-FL are not fully
      understood. Our study was designed to identify cellular mechanisms of
      pathogenesis caused by DUX4-FL expression. METHODS: We used human myogenic cell
      cultures to analyze the effects of DUX4-FL when it was expressed either from its
      endogenous promoter in FSHD cells or by exogenous expression using BacMam
      vectors. We focused on determining the effects of DUX4-FL on protein
      ubiquitination and turnover and on aggregation of TDP-43. RESULTS: Human FSHD
      myotubes with endogenous DUX4-FL expression showed both altered nuclear and
      cytoplasmic distributions of ubiquitinated proteins and aggregation of TDP-43 in
      DUX4-FL-expressing nuclei. Similar changes were found upon exogenous expression
      of DUX4-FL, but were not seen upon expression of the non-toxic short isoform DUX4
      S. DUX4-FL expression also inhibited protein turnover in a model system and
      increased the amounts of insoluble ubiquitinated proteins and insoluble TDP-43.
      Finally, inhibition of the ubiquitin-proteasome system with MG132 produced TDP-43
      aggregation similar to DUX4-FL expression. INTERPRETATIONS: Our results identify
      DUX4-FL-induced inhibition of protein turnover and aggregation of TDP-43, which
      are pathological changes also found in diseases such as amyotrophic lateral
      sclerosis and inclusion body myopathy, as potential pathological mechanisms in
      FSHD.

PMID- 25750921
TI  - SOD1 silencing in motoneurons or glia rescues neuromuscular function in ALS mice.
AB  - OBJECTIVE: Amyotrophic lateral sclerosis is an incurable disorder mainly
      characterized by motoneuron degeneration. Mutations in the superoxide dismutase 1
      (SOD1) gene account for 20% of familial forms of the disease. Mutant SOD1 exerts
      multiple pathogenic effects through the gain of toxic properties in both neurons
      and glial cells. Here, we compare AAV-based gene therapy suppressing expression
      of mutant SOD1 in either motoneurons or astrocytes. METHODS: AAV vectors encoding
      microRNA against human SOD1 were administered to (G93) (A)SOD1 mice either by
      intracerebroventricular injections in pups or by lumbar intrathecal injections in
      adults. Vector systems were designed to suppress SOD1 expression predominantly in
      either spinal motoneurons or astrocytes. Electrophysiological and behavioral
      tests were performed on treated animals to evaluate disease progression. RESULTS:
      Following vector injection in (G93) (A)SOD1 pups, efficient silencing of SOD1
      expression was achieved in motoneurons and/or astrocytes. Most complete
      protection of motor units was obtained when targeting human SOD1 predominantly in
      motoneurons. Suppressing SOD1 mainly in astrocytes led to preserved muscle
      innervation despite only partial protection of spinal motoneurons. In both cases,
      injection in pups led to full recovery of neuromuscular function and
      significantly prolonged survival. Vector injections in adult mice also achieved
      significant protection of neuromuscular function, which was highest when
      motoneurons were targeted. INTERPRETATION: These results suggest that AAV
      mediated SOD1 silencing is an effective approach to prevent motoneuron
      degeneration caused by SOD1 mutation. AAV vectors suppressing SOD1 in motoneurons
      delay disease onset and show effective neuroprotection. On the other hand, AAV
      based SOD1 silencing in astrocytes rescues neuromuscular function following
      initial denervation.

PMID- 25750922
TI  - Functional connectivity changes in the language network during stroke recovery.
AB  - OBJECTIVE: Several neuroimaging studies have examined language reorganization in
      stroke patients with aphasia. However, few studies have examined language
      reorganization in stroke patients without aphasia. Here, we investigated
      functional connectivity (FC) changes after stroke in the language network using
      resting-state fMRI and performance on a verbal fluency (VF) task in patients
      without clinically documented language deficits. METHODS: Early-stage ischemic
      stroke patients (N = 26) (average 5 days from onset), 14 of whom were tested at a
      later stage (average 4.5 months from onset), 26 age-matched healthy control
      subjects (HCs), and 12 patients with cerebrovascular risk factors (patients at
      risk, PR) participated in this study. We examined FC of the language network with
      23 seed regions based on a previous study. We evaluated patients' behavioral
      performance on a VF task and correlation between brain resting-state FC (rsFC)
      and behavior. RESULTS: Compared to HCs, early stroke patients showed
      significantly decreased rsFC in the language network but no difference with
      respect to PR. Early stroke patients showed significant differences in
      performance on the VF task compared to HCs but not PR. Late-stage patients
      compared to HCs and PR showed no differences in brain rsFC in the language
      network and significantly stronger connections compared to early-stage patients.
      Behavioral differences persisted in the late stage compared to HCs. Change in
      specific connection strengths correlated with changes in behavior from early to
      late stage. CONCLUSIONS: These results show decreased rsFC in the language
      network and verbal fluency deficits in early stroke patients without clinically
      documented language deficits.

PMID- 25750923
TI  - The avascular zone and neuronal remodeling of the fovea in Parkinson disease.
AB  - Inner foveal thinning and intracellular alpha-synuclein were demonstrated in the
      retina in Parkinson disease. While pathognomonic alpha-synuclein is associated
      with embryonic dopaminergic (DA) neurons, postmortem studies in the nervous
      system and retina show prominent effect also in non-DA neurons. We evaluated
      foveal capillaries and foveal thickness in 23 Parkinson disease subjects and 13
      healthy controls using retinal fluorescein angiography and optical coherence
      tomography. The size of the foveal avascular zone inversely correlates with
      foveal thinning. Foveal thinning highly correlates with motor impairment and also
      disease duration. Quantifying capillary and neuronal remodeling could serve as
      biological markers. 

PMID- 25750924
TI  - Survival and severity in dominant cerebellar ataxias.
AB  - Inherited spinocerebellar ataxias (SCAs) are known to be genetically and
      clinically heterogeneous. Whether severity and survival are variable, however, is
      not known. We, therefore, studied survival and severity in 446 cases and 509
      relatives with known mutations. Survival was 68 years [95% CI: 65-70] in 223
      patients with polyglutamine expansions versus 80 years [73-84] in 23 with other
      mutations (P < 0.0001). Disability was also more severe in the former: at age 60,
      30% were wheelchair users versus 3% with other SCAs (P < 0.001). This has
      implications for genetic counseling and the design of therapeutic trials. 

PMID- 25750925
TI  - Cuprizone does not induce CNS demyelination in nonhuman primates.
AB  - Cognitive decline is a common symptom in multiple sclerosis patients, with
      profound effects on the quality of life. A nonhuman primate model of multiple
      sclerosis would be best suited to test the effects of demyelination on complex
      cognitive functions such as learning and reasoning. Cuprizone has been shown to
      reliably induce brain demyelination in mice. To establish a nonhuman primate
      model of multiple sclerosis, young adult cynomolgus monkeys were administered
      cuprizone per os as a dietary supplement. The subjects received increasing
      cuprizone doses (0.3-3% of diet) for up to 18 weeks. Magnetic resonance imaging
      and immunohistological analyses did not reveal demyelination in these monkeys. 

PMID- 25750927
TI  - Self-Presentation, Desired Partner Characteristics, and Sexual Behavior
      Preferences in Online Personal Advertisements of Men Seeking Non-Gay-Identified
      Men.
AB  - Despite attention to the sexual behaviors of non-gay-identified (NGI) men who
      have same-sex encounters, virtually no research has focused on issues of partner
      desirability and selection. Limited evidence suggests that a subgroup of men who
      have sex with men (MSM) advertise online for sexual encounters with NGI men.
      Exchange theory provided a framework to investigate this seeking of NGI men,
      based on the content of Internet personal advertisements for same-sex encounters.
      Researchers analyzed 282 ads posted to an online bulletin board. Ads by men who
      explicitly desired encounters with NGI men were compared with those by men who
      did not indicate this preference in potential partners. Multivariate analyses
      revealed that NGI-seeking men had significantly increased odds of identifying as
      discreet (Adjusted odds ratio [AOR] = 2.82), seeking a discreet encounter (AOR =
      4.68), seeking a masculine partner (AOR = 2.18), being willing to host (AOR =
      2.77), as well as seeking oral-receptive sex (AOR = 2.69), unprotected oral sex
      (AOR = 6.76), and anal-receptive sex (AOR = 2.18). Further, NGI-seeking ads were
      more likely to not mention condom use or safer sex practices (AOR = 4.13) and
      were less likely to indicate a desire for oral-insertive sex (AOR = 0.34) and
      rimming (AOR = 0.21). Findings suggest that some men may deliberately present
      themselves in ways that they perceive as being attractive to NGI men, and have
      research implications for NGI MSM, their partners, and the risk outcomes of these
      online ads.

PMID- 25750928
TI  - Nondestructive evaluation of progressive neuronal changes in organotypic rat
      hippocampal slice cultures using ultrahigh-resolution optical coherence
      microscopy.
AB  - Three-dimensional tissue cultures have been used as effective models for studying
      different diseases, including epilepsy. High-throughput, nondestructive
      techniques are essential for rapid assessment of disease-related processes, such
      as progressive cell death. An ultrahigh-resolution optical coherence microscopy
      (UHR-OCM) system with [Formula: see text] axial resolution and [Formula: see
      text] transverse resolution was developed to evaluate seizure-induced neuronal
      injury in organotypic rat hippocampal cultures. The capability of UHR-OCM to
      visualize cells in neural tissue was confirmed by comparison of UHR-OCM images
      with confocal immunostained images of the same cultures. In order to evaluate the
      progression of neuronal injury, UHR-OCM images were obtained from cultures on 7,
      14, 21, and 28 days in vitro (DIVs). In comparison to DIV 7, statistically
      significant reductions in three-dimensional cell count and culture thickness from
      UHR-OCM images were observed on subsequent time points. In cultures treated with
      kynurenic acid, significantly less reduction in cell count and culture thickness
      was observed compared to the control specimens. These results demonstrate the
      capability of UHR-OCM to perform rapid, label-free, and nondestructive evaluation
      of neuronal death in organotypic hippocampal cultures. UHR-OCM, in combination
      with three-dimensional tissue cultures, can potentially prove to be a promising
      tool for high-throughput screening of drugs targeting various disorders. 

PMID- 25750929
TI  - Innate Immune Responses in the Neutrophils of Community Dwelling and Nursing Home
      Elders.
AB  - OBJECTIVE: To evaluate innate immune responses of older disabled nursing home
      residents that may contribute to infectious disease susceptibility, we compared
      surface markers and signaling efficiency of neutrophils from nursing home
      residents and community dwelling elders. DESIGN: Observational pilot study.
      SETTING: Five New Haven, CT area nursing homes and the greater New Haven
      community. PARTICIPANTS: 15 nursing home residents and 43 community dwelling
      elders. MEASUREMENTS: Neutrophils were isolated and Toll-like receptor (TLR) and
      beta2 integrin expression on the surface of unstimulated neutrophils were
      measured via flow cytometry. Chemokine induction was determined by Quantitative
      PCR. RESULTS: Surface expression of TLR4 was elevated among nursing home
      residents compared to community dwellers (mean percent positive cells 33.91 [SE
      2.75] vs. 15.67 [SE 1.58], p<0.001), while expression of the beta2 integrins
      CD11b and CD18 was significantly lower (mean fluorescent intensity 460.8 [SE
      49.1] vs. 632.9 [SE 29.5] for CD11b and 59.6 [SE 7.9] vs. 137.6 [SE 4.6] for
      CD18, p<0.0001). Neutrophils from nursing home residents produced substantially
      reduced levels of chemokines at baseline and after stimulation. CONCLUSIONS:
      Because integrins are an important pathway to phagocyte signaling and contribute
      to adherence and locomotion of neutrophils, reduced beta2 integrin expression may
      contribute to impaired responses to stimulation and reduced adhesive properties
      in PMN from nursing home residents. Since integrin CD11b has been shown to
      negatively regulate TLR4 response, it is plausible that lower levels of CD11b
      contribute to elevated expression of TLR4.

PMID- 25750930
TI  - New Sites for Old Suspects: Environmental Allosteric Modifiers of Nuclear Hormone
      Receptors.

PMID- 25750931
TI  - Memory integration: neural mechanisms and implications for behavior.
AB  - Everyday behaviors require a high degree of flexibility, in which prior knowledge
      is applied to inform behavior in new situations. Such flexibility is thought to
      be supported in part by memory integration, a process whereby related memories
      become interconnected in the brain through recruitment of overlapping neuronal
      populations. Recent advances in cognitive and behavioral neuroscience highlight
      the importance of a hippocampal-medial prefrontal circuit in memory integration.
      Emerging evidence suggests that abstracted representations in medial prefrontal
      cortex guide reactivation of related memories during new encoding events, thus
      promoting hippocampal integration of related experiences. Moreover, recent work
      indicates that integrated memories are called upon during novel situations to
      facilitate a host of behaviors, from spatial navigation to imagination.

PMID- 25750932
TI  - A novel role for KLF14 in T regulatory cell differentiation.
AB  - BACKGROUND AND AIMS: KLF proteins function as epigenetic reprogramming factors
      during cell differentiation in many cell populations and in engineered iPS cells.
      In this study, we determined KLF14 function in the regulation of FOXP3, a
      transcription factor critical for Treg cell differentiation. METHODS: We studied
      the effects of KLF14 on FOXP3 expression at the level of the protein and mRNA. We
      evaluated the functional relevance of KLF14 to FOXP3+ Treg cells in vitro and in
      vivo through suppression assays and two colitis models. Finally, we analyzed the
      effect of KLF14 on the epigenetic landscape of the FOXP3 promoter locus through
      chromatin immuno-precipitation. RESULTS: KLF14, induced upon activation of naive
      CD4+ T cells, segregates to the FOXP3- population and is inversely associated
      with FOXP3 expression and Treg function. KLF14 KO CD4+ cells differentiated into
      adaptive Tregs more readily in vitro and in vivo. KLF14 KO cells demonstrated
      enhanced Treg suppressor function in vitro and in vivo. KLF14 repressed FOXP3 at
      the level of the mRNA and protein, and by ChIP assay KLF14 was found to bind to
      the TSDR enhancer region of FOXP3. Furthermore, loss of KLF14 reduced the levels
      of H3K9me3, HP1 and Suv39H1at the TSDR. CONCLUSIONS: These results outline a
      novel mechanism by which KLF14 regulates Treg cell differentiation via chromatin
      remodeling at the FOXP3 TSDR. To our knowledge, this is the first evidence
      supporting a role for KLF14 in maintaining the differentiated state of Treg cells
      and outlines a potential mechanism to modify the expression of immune genes, such
      as FOXP3, which are critical to T cell fate.

PMID- 25750933
TI  - Circulating Prostaglandin Biosynthesis in Colorectal Cancer and Potential
      Clinical Significance.
AB  - BACKGROUND: Colorectal cancer (CRC) represents the third leading cause of cancer
      related death in the United States. Lack of reliable biomarkers remains a
      critical issue for early detection of CRC. In this study, we investigated the
      potential predictive values of circulating prostaglandin (PG) biosynthesis in CRC
      risk. METHODS: Profiles of circulating PG biosynthesis and platelet counts were
      determined in healthy subjects (n = 16), familial adenomatous polyposis (FAP)
      patients who were classified as regular aspirin users (n = 14) or nonusers (n =
      24), and CRC patients with (n = 18) or without FAP history (n = 20).
      Immunohistochemistry staining was performed on biopsy samples. RESULTS: Analysis
      of circulating PG biosynthesis unexpectedly revealed that CRC progression is
      accompanied by a pronounced elevation of circulating thromboxane A2 (TXA2)
      levels. When a circulating TXA2 level of 1000 pg/mL was selected as a practical
      cutoff point, 95% of CRC patients were successfully identified. Further study
      suggested that the TXA2 pathway is constitutively activated during colorectal
      tumorigenesis and required for anchorage-independent growth of colon cancer
      cells. CONCLUSIONS: This study established the importance of the TXA2 pathway in
      CRC pathophysiology, and laid the groundwork for introducing a TXA2-targeting
      strategy to CRC prevention, early detection and management.

PMID- 25750935
TI  - Osteoarthritis - Why Exercise?

PMID- 25750936
TI  - Increasing Influenza Vaccination Rates in a Busy Urban Clinic.
AB  - Influenza infection is the cause of thousands of hospitalizations and deaths each
      year; infection during pregnancy results in increased morbidity and mortality.
      Underserved women are particularly susceptible to not receiving recommended
      vaccinations. This project explored the effect of a simple paper based prompt on
      the influenza vaccination rate in a resident continuity clinic for the
      underserved. Using this reminder to providers to discuss the influenza
      vaccination with their patients, we were able to increase vaccination rates in
      our clinic from 2.2% to 14.2%. This implementation of a simple, low cost, low
      tech prompt to providers increased the rate of influenza vaccination in our
      clinic and we present this approach as an easy to implement method of improving
      vaccination rates. We also suggest this method as an alternative to an alert in
      the electronic medical record in situations where the electronic medical record
      may not be accessed during every patient encounter.

PMID- 25750938
TI  - Don't Like RDF Reification? Making Statements about Statements Using Singleton
      Property.
AB  - Statements about RDF statements, or meta triples, provide additional information
      about individual triples, such as the source, the occurring time or place, or the
      certainty. Integrating such meta triples into semantic knowledge bases would
      enable the querying and reasoning mechanisms to be aware of provenance, time,
      location, or certainty of triples. However, an efficient RDF representation for
      such meta knowledge of triples remains challenging. The existing standard
      reification approach allows such meta knowledge of RDF triples to be expressed
      using RDF by two steps. The first step is representing the triple by a Statement
      instance which has subject, predicate, and object indicated separately in three
      different triples. The second step is creating assertions about that instance as
      if it is a statement. While reification is simple and intuitive, this approach
      does not have formal semantics and is not commonly used in practice as described
      in the RDF Primer. In this paper, we propose a novel approach called Singleton
      Property for representing statements about statements and provide a formal
      semantics for it. We explain how this singleton property approach fits well with
      the existing syntax and formal semantics of RDF, and the syntax of SPARQL query
      language. We also demonstrate the use of singleton property in the representation
      and querying of meta knowledge in two examples of Semantic Web knowledge bases:
      YAGO2 and BKR. Our experiments on the BKR show that the singleton property
      approach gives a decent performance in terms of number of triples, query length
      and query execution time compared to existing approaches. This approach, which is
      also simple and intuitive, can be easily adopted for representing and querying
      statements about statements in other knowledge bases.

PMID- 25750937
TI  - Elevated Plasma Factor VIII in Patients with Ischemic Stroke: Does it have any
      Association with Hypertensive Heart Disease?
AB  - BACKGROUND: Elevated factor VIII (FVIII) has been linked with higher risk of
      vascular events. We aimed to determine the relationship between FVIII and
      hypertension in patients with acute ischemic stroke. METHODS: FVIII levels and
      transthoracic echocardiogram reports were reviewed in patients with acute
      ischemic stroke who presented to our stroke center between July 2008 and
      September 2011. Presenting systolic and diastolic blood pressure, history of
      hypertention, left ventricular hypertrophy, diastolic dysfunction, and depressed
      left ventricular function (ejection fraction <50%) were compared in patients with
      normal and elevated FVIII levels. RESULTS: No differences in presenting blood
      pressure or frequency of hypertension history were found based on FVIII level.
      Patients with elevated FVIII had demonstrated a statistically significant higher
      frequency of diastolic dysfunction (64.8 vs. 43.6%, p=0.042) and a trend towards
      higher frequency of left ventricular hypertrophy (18.5 vs 5.1%, p=0.073). Median
      FVIII was significantly higher in patients with left ventricular hypertrophy
      (194.4 vs 152.9%, p=0.042) and diastolic dysfunction (180.5 vs 149.3%, p=0.031)
      than patients without these findings. CONCLUSIONS: Among patients with acute
      ischemic stroke, FVIII levels were higher when there was evidence of hypertensive
      heart disease. Synthesis of FVIII may be augmented by the ongoing presence of
      shear stress and could contribute to the higher risk of vaso-occlusive events in
      patients with elevated FVIII.

PMID- 25750934
TI  - Modulation of Bacterial Multidrug Resistance Efflux Pumps of the Major
      Facilitator Superfamily.
AB  - Bacterial infections pose a serious public health concern, especially when an
      infectious disease has a multidrug resistant causative agent. Such multidrug
      resistant bacteria can compromise the clinical utility of major chemotherapeutic
      antimicrobial agents. Drug and multidrug resistant bacteria harbor several
      distinct molecular mechanisms for resistance. Bacterial antimicrobial agent
      efflux pumps represent a major mechanism of clinical resistance. The major
      facilitator superfamily (MFS) is one of the largest groups of solute transporters
      to date and includes a significant number of bacterial drug and multidrug efflux
      pumps. We review recent work on the modulation of multidrug efflux pumps, paying
      special attention to those transporters belonging primarily to the MFS.

PMID- 25750939
TI  - Hsa-miR-331-3p inhibits VHL expression by directly targeting its mRNA 3'-UTR in
      HCC cell lines.
AB  - Dysregulation of miRNA is widely involved in human cancers, including
      hepatocellular carcinoma (HCC). Array data for miRNAs indicated that miR-331-3p
      might be one of the disorderly expressed miRNAs in HCC cell lines, but the
      function of miR-331-3p in HCC remains unclear. In this study, quantitative real
      time polymerase chain reaction (qRT-PCR) results indicated that miR-331-3p was up
      regulated in HepG2.2.15 cells, Ad-HBV-HepG2 cells and pCH9/3091 transfected
      SMMC7721 cells compared with their control group, respectively. miRNA target
      prediction software was used, and VHL was found to be one of the target genes of
      miR-331-3p. qRT-PCR and western blot analysis indicated VHL expression was
      decreased when miR-331-3p was over-expressed and increased when miR-331-3p was
      inhibited in SMMC7721 cells. The luciferase reporter activity was inhibited in
      SMMC7721 cells when co-transfected with miR-331-3p expression vector and VHL 3'
      UTR wild type vector and increased in HepG2.2.15 transfected with miR-331-3p
      inhibitor compared to its control group respectively. When co-transfected with
      miR-331-3p expression vector and VHL 3'-UTR mutated type vector in SMMC7721 cells
      the luciferase reporter activity was recovered. All of these results show that
      HBV up-regulated miR-331-3p expression in HCC cell lines and miR-331-3p could
      inhibit VHL expression by directly targeting its 3'-UTR. This provided useful
      information in exploring the mechanism of HCC induced by HBV infection.

PMID- 25750941
TI  - Patient satisfaction as a metric for quality.

PMID- 25750940
TI  - Inhibition of cell proliferation and induction of apoptosis in K562 human
      leukemia cells by the derivative (3-NpC) from dihydro-pyranochromenes family.
AB  - Leukemia is a particular type of cancer characterized by the failure of cell
      death or disability in differentiation of hematopoietic cells. Chronic myelogenus
      leukemia (CML) is the most studied kind of this cancer. In this study, anti
      cancer effect of dihydro-pyranochromenes derivatives were investigated in the
      human leukemia K562 cells. These compounds were found to be active cell
      proliferation inhibitors using MTT assay. Among these compounds, 3-NpC was
      determined as stronger compound with IC50 value of 100 +/- 3.1 uM and was chosen
      for further studies. Induction of apoptosis was analyzed by AO/EtBr staining, DNA
      fragmentation assay, Annexin V/PI double staining and cell cycle analysis.
      Furthermore, Western Blot analysis showed that treatment of the cells with 3-NpC
      led to up-regulation and activation of caspase-3. The results of this
      investigation clearly indicated that dihydro-pyranochromenes derivatives induce
      apoptosis in the K562 cell line. This information signalizes also that these
      compounds may prepare a new therapeutic approach for the treatment of leukemia.

PMID- 25750942
TI  - A novel treatment for refractory plantar fasciitis.
AB  - Chronic plantar fasciitis is a major health care problem worldwide and affects
      nearly 10% of the US population. Although most cases resolve with conservative
      care, the numerous treatments for refractory plantar fasciitis attest to the lack
      of consensus regarding these cases. The emerging goals for this condition are a
      minimally invasive percutaneous intervention that is safe, effective, and well
      tolerated and has minimal morbidity and a low complication rate. We conducted a
      prospective study in which patients were allowed either to continue with
      noninvasive treatment or to undergo focal aspiration and partial fasciotomy with
      an ultrasonic probe. This is the first report of a plantar fascia partial release
      guided by ultrasonic energy delivered by a percutaneously inserted probe under
      local anesthesia. The procedure appears to be a safe, effective, well-tolerated
      treatment for a condition that is refractory to other options. 

PMID- 25750943
TI  - Potential utility of liposome bupivacaine in orthopedic surgery.
AB  - Management of postsurgical analgesia is an important consideration in orthopedic
      procedures, including joint arthroplasty. Inadequate postsurgical analgesia is
      associated with increased hospital length of stay, delayed ambulation, and
      reduced exercise capacity. In this article, we review the potential contribution
      of a prolonged-release liposomal formulation of bupivacaine as part of a
      multimodal analgesic regimen after orthopedic surgery. Controlled studies across
      multiple surgical settings have demonstrated that, compared with placebo and
      bupivacaine HCl, liposome bupivacaine in a single administration provides
      postsurgical analgesia for up to 72 hours, delays use of rescue medication, and
      reduces postsurgical opioid consumption. Liposome bupivacaine has been well
      tolerated in clinical studies and has had a low rate of treatment-related adverse
      events. To date, there has been no signal of cardiac toxicity, chondrolysis, or
      delayed wound healing associated with liposome bupivacaine. 

PMID- 25750944
TI  - Complications of open reduction and internal fixation of ankle fractures in
      patients with positive urine drug screen.
AB  - We conducted a study to identify complications associated with open treatment of
      ankle fractures in patients who tested positive for illicit drugs on urine drug
      screen (UDS). We hypothesized that patients who had a history of positive UDS and
      underwent open reduction and internal fixation of an ankle fracture would have a
      higher incidence of major and minor complications. We retrospectively reviewed
      the cases of 142 patients who had surgical stabilization of an ankle fracture
      during a 3-year period. Patients with a history of positive UDS were compared
      with matched controls with negative UDS. Outcomes measures included nonunion,
      malunion, and superficial or deep infection. Fisher exact test, Wilcoxon rank sum
      test, and univariate logistic regression were used to determine statistical
      significance. There were no significant differences in age, sex, fracture type,
      incidence of diabetes, or incidence of open fracture between the groups.
      Incidence of nonunion was higher in patients with positive UDS (P = .01), as was
      incidence of deep infection (P = .05). Incidence of pooled major complications
      was also higher in positive UDS patients (P = .03). Patients with a history of
      illicit drug use, as evidenced by positive UDS, are at increased risk for
      perioperative complications during treatment for ankle fracture. 

PMID- 25750945
TI  - Unstable dorsal proximal interphalangeal joint fracture-dislocations treated with
      extension-block pinning.
AB  - Unstable proximal interphalangeal (PIP) joint fracture-dislocations, which can
      cause significant disability, can be treated with multiple techniques. Extension
      block pinning (EBP) allows for early motion and is less technically demanding
      than alternative surgical treatments. In the study reported here, 12 patients
      with unstable dorsal PIP fracture-dislocations were treated with closed reduction
      of the PIP joint followed by percutaneous insertion of a Kirschner wire (K-wire)
      into the distal aspect of the proximal phalanx. For these patients, extent of
      articular surface involvement averaged 43% (range, 25%-75%). Active motion was
      initiated early after surgery, and the K-wire was removed a mean of 25 days after
      pinning. Radiographic reduction of joint dislocation was achieved and maintained
      for 11 of the 12 patients at a mean follow-up of 35.5 months. At follow-up, mean
      visual analog scale (VAS) score was 0.64 (scale, 0-10). Mean score on the Quick
      Disabilities of the Arm, Shoulder, and Hand (QuickDASH) questionnaire was 5.7,
      suggesting minimal functional impairment. Mean PIP active motion was 84 degrees 
      (range, 50 degrees -110 degrees ). Grip strength was equal between operative and
      contralateral hands. Patient satisfaction most closely correlated with low VAS
      and QuickDASH scores. One patient developed a malunion, which was treated with
      corrective osteotomy. EBP is a simple, safe, and reproducible technique for
      unstable PIP fracture-dislocations. This technique yields outcomes similar to
      those reported for more complex surgical procedures. 

PMID- 25750946
TI  - Intraoperative radiofrequency ablation for osteoid osteoma.
AB  - Percutaneous radiofrequency ablation (RFA) has been increasingly used in the
      treatment of osteoid osteoma (OO), as this method has provided satisfactory
      results with minimal morbidity. RFA traditionally has been performed by
      radiologists under computed tomography (CT) guidance. Advances in intraoperative
      imaging techniques now allow orthopedic oncologists to perform image-guided RFA
      in the operating room. We conducted a study to evaluate the efficacy of a novel
      technique that uses intraoperative CT-guided RFA to treat OO. We reviewed 28
      consecutive cases of OO treated with intraoperative RFA by a single surgeon
      between September 2004 and December 2008. Primary or secondary success was
      defined as complete pain relief without evidence of recurrence after the first or
      second procedure, respectively. Failure was defined as the continued presence of
      symptoms combined with radiographic evidence of recurrence. Primary success rate
      was 92.8%. Two patients had a recurrence and underwent a successful second RFA.
      Our success rates are similar to those in the radiology literature. Further
      studies are needed to validate the efficacy of this novel technique. 

PMID- 25750947
TI  - Use of cross-leg flap for wound complications resulting from open pilon fracture.
AB  - Pilon fractures and associated soft-tissue complications present treatment
      challenges for orthopedic surgeons. Open fractures may require additional soft
      tissue coverage. When local soft tissues do not allow for viable coverage, a
      cross-leg flap is available as a salvage procedure with successful outcomes. To
      our knowledge, there have been no previous reports of using cross-leg flaps for
      wound complications in high-energy pilon fractures. 

PMID- 25750948
TI  - Wrisberg-variant discoid lateral meniscus: current concepts, treatment options,
      and imaging features with emphasis on dynamic ultrasonography.
AB  - Discoid lateral menisci represent a range of morphologic abnormalities of the
      lateral meniscus. The Wrisberg-variant discoid lateral meniscus is an unstable
      type that lacks posterior ligament attachments, resulting in "snapping knee
      syndrome." Abnormally mobile discoid lateral menisci are difficult to diagnose
      both clinically and with traditional static imaging, such as magnetic resonance
      imaging. In this article, we discuss the pathophysiology, clinical features,
      imaging findings, and treatment options for Wrisberg-variant discoid lateral
      menisci. We focus on the role of dynamic ultrasonography in revealing lateral
      meniscal subluxation during provocative maneuvers. 

PMID- 25750949
TI  - Meaningful use for surgeons-it's not as complicated as you think.

PMID- 25750950
TI  - Is hemolysis a clinical marker of Propionibacterium acnes orthopedic infection or
      a phylogenetic marker?

PMID- 25750951
TI  - Authors' response.

PMID- 25750952
TI  - Assessment of medical school musculoskeletal education.
AB  - Most medical fields require a basic knowledge of musculoskeletal medicine.
      Although many nonorthopedic clinicians treat musculoskeletal problems, this area
      of medicine is often given little time in medical school curricula. In the study
      reported here, a validated musculoskeletal cognitive evaluation was given to
      medical students before and after a new musculoskeletal module to determine the
      impact of the module on their competency in musculoskeletal medicine. Four
      hundred five students at a single medical school took the examination, which was
      corrected according to a validated scoring system, and the data were subsequently
      analyzed. Mean cognitive examination score was 40%. The recommended mean passing
      score for the examination is 73.1%. Scores were significantly (P < .05) higher
      for the premodule group (42.1%) than the postmodule group (39.1%). Statistical
      significance was set at P < .05. Students' overall mean score was far below
      passing, which demonstrates the inadequacy of musculoskeletal education within
      the medical school curriculum. That the postmodule group scored lower than the
      premodule group suggests that increasing musculoskeletal lecture time may not
      improve medical students' musculoskeletal knowledge. 

PMID- 25750953
TI  - Aneurysmal bone cyst involving the metacarpal bone in a child.
AB  - Aneurysmal bone cysts associated with tubular bones of the hand occur rarely and
      require particular diagnostic and therapeutic management techniques. While
      optimal treatment has not been established, accepted treatments range from
      aggressive radical treatment, including en bloc resection and excision
      diaphysectomy with strut bone grafting, to relatively simple techniques, such as
      thorough curettage followed by bone graft. Aggressive treatment approaches may be
      optimal for the cases with articular surface involvement, full-bone invasion of
      the phalanx or metacarpal, or more than 1 recurrence. We report a monocentric
      case of aneurysmal bone cysts involving metacarpal bone in a child who achieved
      favorable outcome with curettage and morselized cancellous bone grafts. 

PMID- 25750954
TI  - Atypical presentation of fat embolism syndrome after gunshot wound to the foot.
AB  - A 42-year-old man sustained a gunshot wound to the foot, which caused multiple
      fractures of the tarsal bones. Over the course of 6 hours, he became obtunded and
      began to experience respiratory compromise and neurologic symptoms. On magnetic
      resonance imaging, he was found to have innumerable tiny infarcts consistent with
      fat embolism syndrome. He was placed in a spanning external fixator. The patient
      remained in a coma for 6 weeks after injury but gradually regained function. Fat
      embolism syndrome is classically described as resulting from injury to the
      diaphysis of a long bone, but it can occur secondary to trauma of the foot.
      Neurovascular status must be continually evaluated in the setting of any bony
      trauma, and index of suspicion should remain high when neurologic deficits are
      encountered. 

PMID- 25750955
TI  - Harrington rod revision after failed total hip arthroplasty due to missed
      acetabular metastasis.
AB  - We report the case of a 61-year-old woman who was referred to our service after
      she received a total hip implant at another institution and was found to have a
      large acetabular defect from pulmonary metastasis. The patient elected to undergo
      palliative surgical curettage and fixation. We describe a technique to create a
      cement construct reinforced with Steinmann pins that reduces pain and offers
      improved mobility. 

PMID- 25750956
TI  - Glenoid damage from articular protrusion of metal suture anchor after
      arthroscopic rotator cuff repair.
AB  - Arthroscopic repair of rotator cuff tears has been shown to be effective and
      safe. The use of suture anchors has increased the ability to perform rotator cuff
      repairs arthroscopically. However, the use of suture anchors for any surgery
      around the shoulder can result in complications if the devices are not used and
      inserted properly. Complications that have been reported with the use of suture
      anchors for rotator cuff surgery include prominent anchors in the tuberosities,
      dislodged anchors secondary to pull-out or improper insertion, and osteolysis
      around the anchors. We report a case of articular cartilage damage secondary to a
      suture anchor protruding through the humeral head because of improper anchor
      insertion. Our patient's case reminds surgeons not only to be careful of the
      depth of insertion of suture anchors when performing rotator cuff surgery but
      also to obtain radiographs to evaluate the anchor position if patients continue
      to have symptoms after rotator cuff repair using these devices. 

PMID- 25750957
TI  - Intragrade intramedullary nailing of an open tibial shaft fracture in a patient
      with concomitant ipsilateral total knee arthroplasty.
AB  - Open tibial shaft fracture occurring below an ipsilateral total knee arthroplasty
      (TKA) is a unique injury pattern that presents an additional degree of complexity
      to an already challenging treatment algorithm. Tibial shaft fracture is a
      surgical emergency requiring respect for the soft-tissue envelope and
      consideration of the biomechanical and biologic factors involved in healing.
      Treatment with an intramedullary nail relative to other types of internal or
      external fixation methods optimizes these factors and minimizes the risks of
      nonunion, malunion, infection, soft-tissue compromise, and reoperation, which are
      prevalent after this fracture. However, tibial shaft fracture associated with an
      ipsilateral TKA complicates standard treatment principles and increases the risks
      after surgery. In many instances, this type of injury pattern in a patient with
      medical comorbidities that would impede fracture and wound healing would make a
      limb amputation the preferred method of treatment. However, in this case report,
      we examine treatment options for an open tibial shaft fracture in the setting of
      an ipsilateral TKA and propose a method of limb salvage in a patient with medical
      comorbidities sustaining this injury pattern. 

PMID- 25750958
TI  - Nanotechnology: why should we care?

PMID- 25750959
TI  - Can dermatologists influence the political process?

PMID- 25750960
TI  - Modifier -25 use in dermatology.

PMID- 25750961
TI  - Epithelioid sarcoma resembling benign fibrous histiocytoma.
AB  - Epithelioid sarcoma (ES) is a rare malignancy notorious for its tendency to
      histologically mimic granuloma annulare and other palisading granulomatous
      processes. We report a case of ES on the right hand of a 23-year-old man that
      histopathologically resembled a benign fibrous histiocytoma. Superficial portions
      of the tumor were well differentiated, exhibiting spindled and ovoid cells with
      scant cytoplasm that surrounded sclerotic collagen bundles. More obvious atypia
      including greater cellularity, nuclear pleomorphism, and mitotic activity were
      mostly confined to the deep-seated regions of the tumor. In addition to
      palisading granulomatous processes, ES can mimic benign fibrous histiocytoma, and
      the superficial portions of ES may appear deceptively benign. 

PMID- 25750962
TI  - Reflectance confocal microscopy: an effective diagnostic tool for dermatophytic
      infections.
AB  - Current methods for diagnosing dermatophytic infections have various drawbacks.
      Analysis via skin scrapings and biopsies can be invasive and/or take too long to
      yield results. Reflectance confocal microscopy (RCM) is an emerging in vivo
      imaging technology that can potentially be used to diagnose cutaneous
      dermatophytic infections. This modality provides high-resolution images of the
      skin extending to the level of the superficial reticular dermis that could reveal
      the presence of fungal hyphae. In this retrospective chart review, we
      investigated the application of RCM as a diagnostic tool in the setting of a
      private practice. Images were used to diagnose dermatophyte infections and the
      results were compared to those of other established diagnostic methods. We found
      RCM to be a potentially effective and highly sensitive tool in the diagnosis of
      cutaneous dermatophytic infections. 

PMID- 25750963
TI  - Factors affecting academic leadership in dermatology.
AB  - Although prior studies have examined methods by which to recruit and retain
      academic dermatologists, few have examined factors that are important for
      developing academic leaders in dermatology. This study sought to examine
      characteristics of dermatology residency programs that affect the odds of
      producing department or division chairs/chiefs and program directors (PDs). Data
      regarding program size, faculty, grants, alumni residency program attended,
      lectures, and publications for all accredited US dermatology residency programs
      were collected. Of the 103 programs examined, 46% had graduated at least 1
      chair/chief, and 53% had graduated at least 1 PD. Results emphasize that faculty
      guidance and research may represent modifiable factors by which a dermatology
      residency program can increase its graduation of academic leaders. 

PMID- 25750964
TI  - External beam radiotherapy of extramammary Paget disease.
AB  - Extramammary Paget disease (EMPD) is an insidious intraepithelial neoplasm that
      is difficult to control with surgery, as large resections typically are required.
      An effective alternative is external beam radiotherapy (EBRT), which typically
      results in rapid resolution of EMPD. In this study, we analyzed long-term
      outcomes in 7 patients who were treated with EBRT for EMPD. 

PMID- 25750965
TI  - Angioimmunoblastic t-cell lymphoma presenting as purpura fulminans.
AB  - Purpura fulminans is a nonspecific hematologic emergency with high initial
      mortality, representing a thrombotic occlusion of blood vessels leading to skin
      necrosis and disseminated intravascular coagulation, and often reported in the
      setting of sepsis. We report a case of nonfatal purpura fulminans in the context
      of angioimmunoblastic T-cell lymphoma (AITL). 

PMID- 25750966
TI  - What is your diagnosis? acquired lymphangiectasia.

PMID- 25750967
TI  - Pseudoglandular squamous cell carcinoma.

PMID- 25750968
TI  - A primer to natural hair care practices in black patients.
AB  - Natural hairstyles have increased in popularity in the United States among
      individuals of African and Afro-Caribbean descent. Dermatologists should be aware
      of general principles of natural hair care in this patient population, including
      basic hair care terminology, types of natural hairstyles, methods of washing, and
      product selection. A basic knowledge of natural hair care practices in black
      patients will assist dermatologists in the management and treatment of many
      conditions associated with traumatic hairstyling in this patient population. 

PMID- 25750969
TI  - Tense bullae with widespread erosions.

PMID- 25750970
TI  - Dermatologic toxicity in a patient receiving liposomal doxorubicin.

PMID- 25750971
TI  - Multiple papules on the eyelid margin.

PMID- 25750972
TI  - Superficial acral fibromyxoma and other slow-growing tumors in acral areas.
AB  - Superficial acral fibromyxoma (SAFM) is a rare fibromyxoid mesenchymal tumor with
      a predilection for the distal extremities and frequent nail bed involvement.
      Superficial acral fibromyxoma typically arises as a solitary, slow-growing nodule
      on a toe or finger, with the great toe being the most commonly affected site.
      Histopathologically, SAFM characteristically presents as a well-circumscribed but
      unencapsulated dermal tumor composed of spindle and stellate cells in a loose
      storiform or fascicular arrangement embedded in a myxoid, myxocollagenous, or
      collagenous stroma. The tumor often occupies the entire dermis and may extend
      into the subcutis and occasionally the underlying fascia and bone. The
      characteristic immunohistochemical profile of SAFM includes expression of CD34,
      epithelial membrane antigen (EMA), and CD99; it is notably negative for S-100
      protein. We report 3 cases of SAFM and also provide a review of the literature on
      the clinical and histopathologic presentations of this unique entity as well as
      the differential diagnosis. 

PMID- 25750973
TI  - Imiquimod induces sustained remission of actinic damage: a case report spanning
      one decade of observation.
AB  - Actinic keratosis (AK), basal cell carcinoma (BCC), and squamous cell carcinoma
      (SCC) are strongly linked to chronic UV radiation exposure. Although surgical
      treatment is necessary for advanced skin cancers, the use of topical 5
      fluorouracil (5-FU) and imiquimod are well established for treatment of early
      skin cancers and as field therapy for diffuse actinic damage. We present the case
      of a patient who underwent field therapy with topical 5-FU for diffuse actinic
      damage and AKs and showed no inflammatory response within the perimeter of a
      prior BCC that had been treated with imiquimod 10 years prior. In addition to the
      drug effects of imiquimod on atypical keratinocytes, it also may have
      photoprotective effects. 

PMID- 25750974
TI  - Waxy indurated plaques on the eyelids.

PMID- 25750975
TI  - Dermatologic emergencies.
AB  - Although dermatology may be regarded as a medical specialty with few emergencies,
      they do exist and range from primary cutaneous disorders to severe systemic
      conditions with skin manifestations. Prompt recognition for appropriate diagnosis
      and treatment often is necessary to improve a patient's prognosis and a single
      decision can mark the difference between life and death. 

PMID- 25750976
TI  - Tuberculosis cutis orificialis in an immunocompetent patient.

PMID- 25750977
TI  - An unusual case of sporadic hereditary leiomyomatosis and renal cell carcinoma
      syndrome.

PMID- 25750978
TI  - Simple preparation of positively charged silver nanoparticles for detection of
      anions by surface-enhanced Raman spectroscopy.
AB  - Modification of citrate and hydroxylamine reduced Ag colloids with thiocholine
      bromide, a thiol functionalized quaternary ammonium salt, creates particles where
      the zeta potential is switched from the normal values of ca.-50 mV to ca. +50 mV.
      These colloids are stable but can be aggregated with metal salts in much the same
      way as the parent colloids. They are excellent SERS substrates for detection of
      anionic targets since their positive zeta potentials promote adsorption of
      negatively charged ions. This is important because the vast majority of published
      SERS studies involve cationic or neutral targets. Moreover, the fact that the
      modifier is a quaternary ammonium ion means that the negative surface charge is
      maintained even at alkaline pH. The modified colloids can be used to detect
      compounds which cannot be detected using conventional negatively-charged citrate
      or hydroxylamine reduced metal nanoparticles, for example the detection limit was
      5.0 * 10(-5) M for perchlorate and <8.7 * 10(-7) M for tetraphenylporphine
      tetrasulfonic acid (TPPS). More importantly, picric acid (an explosive) and
      diclofenac (a non-steroidal anti-inflammatory) could also be analysed
      quantitatively at low concentrations, 2.5 * 10(-5) M and 1.9 * 10(-5) M,
      respectively. Interestingly, the correct choice of aggregating agent is important
      for achieving high sensitivity since the anion in the aggregating salt may
      compete with anionic targets for surface binding sites. Finally, since the
      modification procedure simply involves reaction of nanoparticles with a small
      alkyl thiol derivative, it can easily be adapted to other particle morphologies
      or metals. 

PMID- 25750979
TI  - Fouling in microstructured devices: a review.
AB  - Microstructured devices are widely used for manufacturing products that benefit
      from process intensification, with pharmaceutical products or specialties of the
      chemical industry being prime examples. These devices are ideally used for
      processing pure fluids. Where particulate or non-pure flows are involved,
      processes are treated with utmost caution since related fouling and blocking
      issues present the greatest barrier to operating microstructured devices
      effectively. Micro process engineering is a relatively new research field and
      there is limited understanding of fouling in these dimensions and its underlying
      processes and phenomena. A comprehensive review on fouling in microstructured
      devices would be helpful in this regard, but is currently lacking. This paper
      attempts to review recent developments of fouling in micro dimensions for all
      fouling categories (crystallization, particulate, chemical reaction, corrosion
      and biological growth fouling) and the sequential events involved (initiation,
      transport, attachment, removal and aging). Compared to fouling in macro
      dimensions, an additional sixth category is suggested: clogging by gas bubbles.
      Most of the reviewed papers present very specific fouling investigations making
      it difficult to derive general rules and parameter dependencies, and comparative
      or critical considerations of the studies were difficult. We therefore used a
      statistical approach to evaluate the research in the field of fouling in
      microchannels. 

PMID- 25750980
TI  - Origin of SMM behaviour in an asymmetric Er(III) Schiff base complex: a combined
      experimental and theoretical study.
AB  - An asymmetric erbium(III) Schiff base complex [Er(HL)2(NO3)3] was synthesized
      which shows SMM behaviour with an Ueff of 5.2 K. Dipolar interaction in 1
      significantly reduced upon dilution which increases the barrier height to 51.5 K.
      Ab initio calculations were performed to shed light on the mechanism of
      magnetization relaxation.

PMID- 25750981
TI  - Aggregation-based abrupt crystallization from amorphous Ag2S to Ag2S
      nanocrystals.
AB  - Abrupt crystallization from ~2-5 nm (amorphous) to ~12-15 nm (crystalline) was
      observed in hydrothermal coarsening of Ag2S. The desorption behavior of capping
      ligands could be associated with the aggregation and fusion of amorphous
      particles into crystals. 

PMID- 25750982
TI  - A multi-functional oil-water separator from a selectively pre-wetted
      superamphiphobic paper.
AB  - A multi-functional oil-water separator is prepared from a paper towel spray
      coated with superamphiphobic (i.e., superhydrophobic and superoleophobic)
      nanoparticles. After the separator is pre-wetted with ethanol, followed by water,
      water can be removed from the light oil-water mixture and emulsions by gravity
      with high separation efficiency (99.9%) and separation flux. Vice versa, heavy
      oil can be removed by gravity on an ethanol-oil pre-wetted SA-paper. 

PMID- 25750983
TI  - Atomistic study of dynamics for metallic filament growth in conductive-bridge
      random access memory.
AB  - The growth dynamics for metallic filaments in conductive-bridge resistive
      switching random access memory (CBRAM) are studied using the kinetic Monte Carlo
      (KMC) method. The physical process at the atomistic level is revealed in
      explaining the experimental observation that filament growth can originate at
      either the cathode or the anode. The statistical nature of the filament growth is
      best shown by the random topography of dendrite-like conductive paths obtained.
      Critical material properties, such as charged-particle mobility in the switching
      layer of a solid electrolyte or a dielectric, are mapped to KMC model parameters
      through activation energy, etc. The accuracy of the simulator is established by
      the good agreement between the simulated forming time and the measured data. 

PMID- 25750984
TI  - Possible association between phantom vibration syndrome and occupational burnout.
AB  - BACKGROUND: Phantom vibration syndrome (PVS) and phantom ringing syndrome (PRS)
      occur in many cell phone users. Previous studies have indicated an association
      between PVS/PRS and job stress. The aim of this study was to determine if PVS/PRS
      were also associated with occupational burnout. METHODS: This was a cross
      sectional study of 384 employees of a high-tech company in northern Taiwan. They
      all completed a phantom vibration and ringing questionnaire, the Hospital Anxiety
      and Depression Scale, and the Chinese version of the Occupational Burnout
      Inventory. RESULTS: Significantly more women and people with at least a college
      education were in the population with PRS and PVS, respectively. Anxiety and
      depression had no associations with PVS/PRS. Higher scores for personal fatigue,
      job fatigue, and service target fatigue had an independent impact on the presence
      of PVS, but only a higher score for service target fatigue had an independent
      impact on the presence of PRS. CONCLUSION: The independent association between
      work-related burnout and PVS/PRS suggests that PVS/PRS may be a harbinger of
      mental stress or a component of the clinical burnout syndrome, and may even be a
      more convenient and accurate predictor of occupational burnout.

PMID- 25750986
TI  - Energetics of order-disorder in layered magnesium aluminum double hydroxides with
      interlayer carbonate.
AB  - Laboratory synthesis of layered double hydroxides (LDH) often results in
      materials replete with stacking faults. Faults are known to affect several
      properties including sorption, electrochemical, and catalytic activity of this
      important class of materials. Understanding the occurrence of faults thus calls
      for a comprehensive analysis of formation and stability of ordered and faulted
      LDHs. High-temperature oxide melt solution calorimetric measurements made on an
      ordered and a faulted Mg-Al LDH with carbonate interlayer anion shows that
      ordered LDH is energetically more stable than the faulted one by ~6 kJ/mol. The
      stacking faults are an intergrowth of 3R1 and 2H1 polytypes, and faults could
      thus mediate transformation of 3R1 to 2H1 polytypes. Several factors including pH
      and temperature of precipitation also affect layer stacking. The formation of
      stacking faults could therefore have its origin in kinetics. Water content in the
      interlayer also affects layer stacking, and hence it may affect properties of
      LDH. Improved understanding of the distribution of water molecules in LDH is also
      crucial in an environmental context, as LDH occur as minerals and are important
      for contaminant amelioration in the environment. Water adsorption calorimetry on
      dehydrated LDH shows a continuous decrease in the magnitude of adsorption
      enthalpy with increasing coverage, indicating the presence of energetically
      heterogeneous sites where the water molecules reside. The results also indicate
      that the energy of several sites where the water molecules may reside (whether in
      the interlayer or on the surface) overlaps, and hence it is hard to differentiate
      among them. 

PMID- 25750985
TI  - Identification and validation of novel small molecule disruptors of HuR-mRNA
      interaction.
AB  - HuR, an RNA binding protein, binds to adenine- and uridine-rich elements (ARE) in
      the 3'-untranslated region (UTR) of target mRNAs, regulating their stability and
      translation. HuR is highly abundant in many types of cancer, and it promotes
      tumorigenesis by interacting with cancer-associated mRNAs, which encode proteins
      that are implicated in different tumor processes including cell proliferation,
      cell survival, angiogenesis, invasion, and metastasis. Drugs that disrupt the
      stabilizing effect of HuR upon mRNA targets could have dramatic effects on
      inhibiting cancer growth and persistence. In order to identify small molecules
      that directly disrupt the HuR-ARE interaction, we established a fluorescence
      polarization (FP) assay optimized for high throughput screening (HTS) using HuR
      protein and an ARE oligo from Musashi RNA-binding protein 1 (Msi1) mRNA, a HuR
      target. Following the performance of an HTS of ~6000 compounds, we discovered a
      cluster of potential disruptors, which were then validated by AlphaLISA
      (Amplified Luminescent Proximity Homogeneous Assay), surface plasmon resonance
      (SPR), ribonucleoprotein immunoprecipitation (RNP IP) assay, and luciferase
      reporter functional studies. These compounds disrupted HuR-ARE interactions at
      the nanomolar level and blocked HuR function by competitive binding to HuR. These
      results support future studies toward chemical probes for a HuR function study
      and possibly a novel therapy for HuR-overexpressing cancers. 

PMID- 25750987
TI  - Synthesis and evaluation of hydroxymethylaminocyclitols as glycosidase
      inhibitors.
AB  - Four series of C7N aminocyclitol analogues of glucose were synthesized by
      stereocontrolled epoxide opening of hydroxyl protected forms of the cyclohexane
      epoxides cyclophellitol and 1,6-epi-cyclophellitol. The resulting hydroxymethyl
      substituted aminocyclitols were tested as glycosidase inhibitors. Cyclitols
      having an amino group in an alpha configuration at a position equivalent to the
      anomeric in the sugar were found to be low micromolar inhibitors of the alpha
      glucosidase from baker's yeast with Ki's near to 2 MUM. On the other hand, N
      octyl aminocyclitols having the nitrogen substituents in an alpha or beta
      configuration were found to be good inhibitors of recombinant beta
      glucocerebrosidase with Ki values between 8.3 and 17 MUM, and also inhibited
      lysosomal beta-glucosidase activity in live cells at low-micromolar
      concentrations. A computational docking study suggests a differential binding
      among the different series of beta-glucocerebrosidase inhibitors. In agreement
      with the experimental results, the binding poses obtained indicate that the
      presence of an alkyl lipid substituent in the inhibitor mimicking one of the
      lipid chains in the substrate is critical for potency. In contrast, the matching
      of hydroxymethyl substituents in the aminocyclitols and the parent
      glucosylceramide does not seem to be strictly necessary for potent inhibition,
      indicating the risk of simplifying structural analogies in sugar mimetic design. 

PMID- 25750988
TI  - Integration of ion-exchange and nanofiltration processes for recovering Cr(III)
      salts from synthetic tannery wastewater.
AB  - This study aims to investigate the possibility of integrating both ion-exchange
      (IX) and nanofiltration (NF) processes for the recovery of Cr(III) salts from a
      synthetic solution prepared with concentrations of Cr(III), [Formula: see text]
      and Cl(-) in the range of industrial effluents of tanneries. Ion exchange should
      be used as a pre-treatment for uptaking Cl(-) ions from the effluent, and
      thereafter the treated solution is fed to an NF unit to recover chromium sulphate
      salt for reuse in the tanning bath. The strong anionic resin Diaion PA316 was
      selected for evaluating chloride-sulphate ion-exchange equilibrium, with respect
      to mass of resin, NaCl concentration, temperature and ratio [Formula: see text].
      It was observed that the separation factor, [Formula: see text], depends on the
      total electrolyte concentration and the ratio [Formula: see text] plays a role as
      well. Moreover, it was determined that the resin prefers sulphate over chloride
      since [Formula: see text] is less than 1. The performance of the NF process is
      dependent on [Formula: see text] and the rejection of Cr(III) may decrease from
      90% to 70% as the ratio increases from 0.5 to 2. Regarding the integration of
      both IX and NF, the feed solution after treatement with the resin was fed to NF
      where the ratio of [Formula: see text] led to the best operating conditions for
      this process (90% of Cr(III) rejection and up to 77% for [Formula: see text]
      ions). This strategy may be considered as a sustainable approach since it permits
      to obtain a solution enriched in Cr(III) salt for reuse in the tanning process,
      thus contributing to environmental protection. 

PMID- 25750989
TI  - Green Alternatives to Nitrates and Nitrites in Meat-based Products-A Review.
AB  - Several food additives are added in food for their preservation to maintain the
      freshness of food (antioxidants) or to slow down or stop the growth of
      microorganisms (preservative agents). Nitrites and nitrates are used as
      preservative agents in meat. Nitrites give a smoked taste, a pinkish color in the
      meat and protect the consumers against the risk of bacterial deterioration. Their
      addition is however very limited as, in high dose, it can have risks on human
      health and the environment. Nitrites may also combine with secondary or tertiary
      amines to form N-nitroso derivatives. Certain N-nitroso compounds have been shown
      to produce cancers in a wide range of laboratory animals. Thus, alternatives of
      nitrates and nitrites are the object of numerous research studies. Alternatives,
      such as the addition of vitamins, fruits, chemicals products, natural products
      containing nitrite or spices, which have similar properties of nitrites, are in
      evaluation. In fact, spices are considered to have several organoleptic and anti
      microbial properties which would be interesting to study. Several spices and
      combinations of spices are being progressively evaluated. This review discusses
      the sources of nitrites and nitrates, their use as additives in food products,
      their physicochemical properties, their negatives effects and the use of
      alternatives of nitrites and nitrates in preserving meat products. 

PMID- 25750990
TI  - An Escherichia coli strain, PGB01, isolated from feral pigeon Faeces, thermally
      fit to survive in pigeon, shows high level resistance to trimethoprim.
AB  - In this study, of the hundred Escherichia coli strains isolated from feral Pigeon
      faeces, eighty five strains were resistant to one or more antibiotics and fifteen
      sensitive to all the antibiotics tested. The only strain (among all antibiotic
      resistant E. coli isolates) that possessed class 1 integron was PGB01. The
      dihydrofolate reductase gene of the said integron was cloned, sequenced and
      expressed in E. coli JM109. Since PGB01 was native to pigeon's gut, we have
      compared the growth of PGB01 at two different temperatures, 42 degrees C (normal
      body temperature of pigeon) and 37 degrees C (optimal growth temperature of E.
      coli; also the human body temperature), with E. coli K12. It was found that PGB01
      grew better than the laboratory strain E. coli K12 at 37 degrees C as well as at
      42 degrees C. In the thermal fitness assay, it was observed that the cells of
      PGB01 were better adapted to 42 degrees C, resembling the average body
      temperature of pigeon. The strain PGB01 also sustained more microwave mediated
      thermal stress than E. coli K12 cells. The NMR spectra of the whole cells of
      PGB01 varied from E. coli K12 in several spectral peaks relating some metabolic
      adaptation to thermotolerance. On elevating the growth temperature from 37
      degrees C to 42 degrees C, susceptibility to kanamycin (both strains were
      sensitive to it) of E. coli K12 was increased, but in case of PGB01 no change in
      susceptibility took place. We have also attempted to reveal the basis of
      trimethoprim resistance phenotype conferred by the dfrA7 gene homologue of PGB01.
      Molecular Dynamics (MD) simulation study of docked complexes, PGB01-DfrA7 and E.
      coli TMP-sensitive-Dfr with trimethoprim (TMP) showed loss of some of the
      hydrogen and hydrophobic interaction between TMP and mutated residues in PGB01
      DfrA7-TMP complex compared to TMP-sensitive-Dfr-TMP complex. This loss of
      interaction entails decrease in affinity of TMP for PGB01-DfrA7 compared to TMP
      sensitive-Dfr. 

PMID- 25750991
TI  - Observational and modeling constraints on global anthropogenic enrichment of
      mercury.
AB  - Centuries of anthropogenic releases have resulted in a global legacy of mercury
      (Hg) contamination. Here we use a global model to quantify the impact of
      uncertainty in Hg atmospheric emissions and cycling on anthropogenic enrichment
      and discuss implications for future Hg levels. The plausibility of sensitivity
      simulations is evaluated against multiple independent lines of observation,
      including natural archives and direct measurements of present-day environmental
      Hg concentrations. It has been previously reported that pre-industrial enrichment
      recorded in sediment and peat disagree by more than a factor of 10. We find this
      difference is largely erroneous and caused by comparing peat and sediment against
      different reference time periods. After correcting this inconsistency, median
      enrichment in Hg accumulation since pre-industrial 1760 to 1880 is a factor of
      4.3 for peat and 3.0 for sediment. Pre-industrial accumulation in peat and
      sediment is a factor of ~ 5 greater than the precolonial era (3000 BC to 1550
      AD). Model scenarios that omit atmospheric emissions of Hg from early mining are
      inconsistent with observational constraints on the present-day atmospheric,
      oceanic, and soil Hg reservoirs, as well as the magnitude of enrichment in
      archives. Future reductions in anthropogenic emissions will initiate a decline in
      atmospheric concentrations within 1 year, but stabilization of subsurface and
      deep ocean Hg levels requires aggressive controls. These findings are robust to
      the ranges of uncertainty in past emissions and Hg cycling.

PMID- 25750992
TI  - Nepenthesin protease activity indicates digestive fluid dynamics in carnivorous
      nepenthes plants.
AB  - Carnivorous plants use different morphological features to attract, trap and
      digest prey, mainly insects. Plants from the genus Nepenthes possess specialized
      leaves called pitchers that function as pitfall-traps. These pitchers are filled
      with a digestive fluid that is generated by the plants themselves. In order to
      digest caught prey in their pitchers, Nepenthes plants produce various hydrolytic
      enzymes including aspartic proteases, nepenthesins (Nep). Knowledge about the
      generation and induction of these proteases is limited. Here, by employing a FRET
      (fluorescent resonance energy transfer)-based technique that uses a synthetic
      fluorescent substrate an easy and rapid detection of protease activities in the
      digestive fluids of various Nepenthes species was feasible. Biochemical studies
      and the heterologously expressed Nep II from Nepenthes mirabilis proved that the
      proteolytic activity relied on aspartic proteases, however an acid-mediated auto
      activation mechanism was necessary. Employing the FRET-based approach, the
      induction and dynamics of nepenthesin in the digestive pitcher fluid of various
      Nepenthes plants could be studied directly with insect (Drosophila melanogaster)
      prey or plant material. Moreover, we observed that proteolytic activity was
      induced by the phytohormone jasmonic acid but not by salicylic acid suggesting
      that jasmonate-dependent signaling pathways are involved in plant carnivory. 

PMID- 25750994
TI  - Personal reflections on exploring social media in medicine.
AB  - Social media is difficult to explain to a physician who has never used it. The
      medical literature on its pitfalls and abuses has overshadowed its positive
      applications and made many physicians wary of it. While I was initially reluctant
      to develop my own presence on social media, since embracing it as a tool for
      teaching and learning I have developed a different perspective. I see it as a
      tool that can be used positively or negatively. Much like a megaphone, it can
      amplify our voice so that the impact of our work can extend beyond the borders of
      our institutions and countries. Aided by the guidance and support of mentors who
      used social media before and alongside me, it has helped me to become a more
      competent, professional, engaged, and impactful physician. Within this article I
      will share my story to illustrate the many ways that social media can be used to
      enhance the profession of medicine. 

PMID- 25750993
TI  - Lipid from infective L. donovani regulates acute myeloid cell growth via
      mitochondria dependent MAPK pathway.
AB  - The microbial source, which includes live, attenuated, or genetically modified
      microbes or their cellular component(s) or metabolites, has gained increasing
      significance for therapeutic intervention against several pathophysiological
      conditions of disease including leukemia, which remains an incurable disease till
      now despite recent advances in the medical sciences. We therefore took up the
      present study to explore if the leishmanial lipid (pLLD) isolated from L.
      donovani can play an anti-neoplastic role in acute myeloid leukemia cells by
      regulating cellular growth. Indeed pLLD significantly inhibited cell
      proliferation of four AML cell lines (HL-60, MOLT-4, U937, and K562). Scanning
      electron microscopy and DNA fragmentation analysis revealed that it significantly
      induced apoptosis of U937 cells through morphological alteration. Occurrence of
      apoptosis was checked by using Annexin exposure and this established that the
      cell cycle was arrested at G0/G1 phase in time-dependent manner. pLLD increased
      the intracellular ROS with alteration of mitochondrial membrane potential, as
      detected using DCFDA. It also regulated the expression of apoptosis-related
      proteins like Bax, Bcl2, Bad and t-Bid besides causing cleavage of PARP as
      determined by western blot analysis. Treatment of U937 cells with pLLD induced
      the activation of extracellular signal-regulated kinase (ERK)1/2, c-Jun N
      terminal kinase (JNK)1/2, p38, and caspases 9/3. The results suggest that pLLD
      induces apoptosis in acute myeloid leukemia cells possibly via increasing
      intracellular ROS and regulating the MAPK pathway. 

PMID- 25750995
TI  - Total syntheses and initial evaluation of [Psi[C(?S)NH]Tpg4]vancomycin,
      [Psi[C(?NH)NH]Tpg4]vancomycin, [Psi[CH2NH]Tpg4]vancomycin, and their (4
      chlorobiphenyl)methyl derivatives: synergistic binding pocket and peripheral
      modifications for the glycopeptide antibiotics.
AB  - Full details of studies are disclosed on the total syntheses of binding pocket
      analogues of vancomycin bearing the peripheral L-vancosaminyl-1,2-D-glucosyl
      disaccharide that contain changes to a key single atom in the residue-4 amide
      (residue-4 carbonyl O -> S, NH, H2) designed to directly address the underlying
      molecular basis of resistance to vancomycin. Also disclosed are studies piloting
      the late-stage transformations conducted on the synthetically more accessible C
      terminus hydroxymethyl aglycon derivatives and full details of the peripheral
      chlorobiphenyl functionalization of all of the binding-pocket-modified vancomycin
      analogues designed for dual D-Ala-D-Ala/D-Ala-D-Lac binding. Their collective
      assessment indicates that combined binding pocket and chlorobiphenyl peripherally
      modified analogues exhibit a remarkable spectrum of antimicrobial activity (VSSA,
      MRSA, and VanA and VanB VRE) and impressive potencies against both vancomycin
      sensitive and vancomycin-resistant bacteria (MICs = 0.06-0.005 and 0.5-0.06
      MUg/mL for the amidine and methylene analogues, respectively) and likely benefit
      from two independent and synergistic mechanisms of action, only one of which is
      dependent on D-Ala-D-Ala/D-Ala-D-Lac binding. Such analogues are likely to
      display especially durable antibiotic activity that is not prone to rapidly
      acquired clinical resistance.

PMID- 25750996
TI  - Accumulation of advanced glycation end-products and activation of the SCAP/SREBP
      Lipogenetic pathway occur in diet-induced obese mouse skeletal muscle.
AB  - Aim of this study was to investigate whether advanced glycation end-products
      (AGEs) accumulate in skeletal myofibers of two different animal models of
      diabesity and whether this accumulation could be associated to myosteatosis. Male
      C57Bl/6j mice and leptin-deficient ob/ob mice were divided into three groups and
      underwent 15 weeks of dietary manipulation: standard diet-fed C57 group (C57, n =
      10), high-fat high-sugar diet-fed C57 group (HFHS, n = 10), and standard diet-fed
      ob/ob group (OB/OB, n = 8). HFHS mice and OB/OB mice developed glycometabolic
      abnormalities in association with decreased mass of the gastrocnemius muscle,
      fast-to-slow transition of muscle fibers, and lipid accumulation (that occurred
      preferentially in slow compared to fast fibers). Moreover, we found in muscle
      fibers of HFHS and OB/OB mice accumulation of AGEs that was preferential for the
      lipid-accumulating cells, increased expression of the lipogenic pathway
      SCAP/SREBP, and co-localisation between AGEs and SCAP-(hyper)expressing cells
      (suggestive for SCAP glycosylation). The increased expression of the SCAP/SREBP
      lipogenic pathway in muscle fibers is a possible mechanism underlying lipid
      accumulation and linking myosteatosis to muscle fiber atrophy and fast-to-slow
      transition that occur in response to diabesity. 

PMID- 25750997
TI  - Age differences in prospective memory for everyday life intentions: A diary
      approach.
AB  - The age benefit found in many naturalistic prospective memory (PM) tasks has been
      taken as evidence that PM performance in real life may be spared from aging.
      However, this conclusion lacks empirical confirmation. Hence, the aim of the
      present study was to examine possible age differences in the content of everyday
      PM intentions and their performance. Everyday PM was assessed in young and older
      adults using a diary approach. Results confirmed a general age benefit for real
      life PM tasks. Importantly, this finding was qualified by revealing that the
      benefit only held true for specific types of intentions such as health and social
      intentions. Further, moderation analyses showed that the relationships between
      cognitive functioning and everyday PM were different for young and older adults.
      While better inhibition, short-term and long-term memory were related with
      successful PM performance in the young, this was not the case in the older
      adults. The present findings suggest that the age benefit found in naturalistic
      experimenter-given tasks extends to real-life PM performance, but may differ
      depending on the type of intention. Furthermore, cognitive functioning predicts
      performance in the young, but not in the older adults. 

PMID- 25750998
TI  - Economic well-being among older-adult households: variation by veteran and
      disability status.
AB  - This analysis uses data from the Survey of Income and Program Participation
      (SIPP) to examine whether veteran and disability statuses are jointly associated
      with poverty and material hardship among households that include an older adult.
      Compared to households that do not include a person with a disability or veteran,
      disabled nonveteran households are more likely to be in poverty and to experience
      home hardship, medical hardship, and bill-paying hardship. Disabled veteran
      households are not significantly different in terms of poverty, but exhibit the
      highest odds of home hardship, medical hardship, bill-paying hardship, and food
      insufficiency. The implications for social work practice are discussed. 

PMID- 25751000
TI  - Parent Management Training and Collaborative & Proactive Solutions: A Randomized
      Control Trial for Oppositional Youth.
AB  - This study examined the efficacy of Collaborative & Proactive Solutions (CPS) in
      treating oppositional defiant disorder (ODD) in youth by comparing this novel
      treatment to Parent Management Training (PMT), a well-established treatment, and
      a waitlist control (WLC) group. One hundred thirty-four youth (ages 7-14, 61.9%
      male, 83.6% White) who fulfilled Diagnostic and Statistical Manual of Mental
      Disorders (4th ed.) criteria for ODD were randomized to CPS, PMT, or WLC groups.
      ODD was assessed with semistructured diagnostic interviews, clinical global
      severity and improvement ratings, and parent report measures. Assessments were
      completed pretreatment, posttreatment, and at 6 months following treatment.
      Responder and remitter analyses were undertaken using intent-to-treat mixed
      models analyses. Chronological age, gender, and socioeconomic status as well as
      the presence of comorbid attention deficit/hyperactivity and anxiety disorders
      were examined as predictors of treatment outcome. Both treatment conditions were
      superior to the WLC condition but did not differ from one another in either our
      responder or remitter analyses. Approximately 50% of youth in both active
      treatments were diagnosis free and were judged to be much or very much improved
      at posttreatment, compared to 0% in the waitlist condition. Younger age and
      presence of an anxiety disorder predicted better treatment outcomes for both PMT
      and CPS. Treatment gains were maintained at 6-month follow-up. CPS proved to be
      equivalent to PMT and can be considered an evidence-based, alternative treatment
      for youth with ODD and their families.

PMID- 25750999
TI  - Oral administration of recombinant Neisseria meningitidis PorA genetically fused
      to H. pylori HpaA antigen increases antibody levels in mouse serum, suggesting
      that PorA behaves as a putative adjuvant.
AB  - The Neisseria meningitidis outer membrane protein PorA from a Chilean strain was
      purified as a recombinant protein. PorA mixed with AbISCO induced bactericidal
      antibodies against N. meningitidis in mice. When PorA was fused to the
      Helicobacter pylori HpaA antigen gene, the specific response against H. pylori
      protein increased. Splenocytes from PorA-immunized mice were stimulated with
      PorA, and an increase in the secretion of IL-4 was observed compared with that of
      IFN-gamma. Moreover, in an immunoglobulin sub-typing analysis, a substantially
      higher IgG1 level was found compared with IgG2a levels, suggesting a Th2-type
      immune response. This study revealed a peculiar behavior of the purified
      recombinant PorA protein per se in the absence of AbISCO as an adjuvant.
      Therefore, the resistance of PorA to proteolytic enzymes, such as those in the
      gastrointestinal tract, was analyzed, because this is an important feature for an
      oral protein adjuvant. Finally, we found that PorA fused to the H. pylori HpaA
      antigen, when expressed in Lactococcus lactis and administered orally, could
      enhance the antibody response against the HpaA antigen approximately 3 fold.
      These observations strongly suggest that PorA behaves as an effective oral
      adjuvant.

PMID- 25751001
TI  - Low-interference washing-free electrochemical immunosensor using glycerol-3
      phosphate dehydrogenase as an enzyme label.
AB  - In washing-free electrochemical detection, various redox and reactive species
      cause significant interference. To minimize this interference, we report a
      washing-free electrochemical immunosensor using flavin adenine dinucleotide (FAD)
      dependent glycerol-3-phosphate dehydrogenase (GPDH) and glycerol-3-phosphate (GP)
      as an enzyme label and its substrate, respectively, because the reaction of FAD
      dependent dehydrogenases with dissolved O2 is slow and the level of GP
      preexisting in blood is low (<0.1 mM). A combination of a low electrocatalytic
      indium-tin oxide (ITO) electrode and fast electron-mediating Ru(NH3)6(3+) is
      employed to obtain a high signal-to-background ratio via proximity-dependent
      electron mediation of Ru(NH3)6(3+) between the ITO electrode and the GPDH label.
      Electrochemical oxidation of GPDH-generated Ru(NH3)6(2+) is performed at 0.05 V
      vs Ag/AgCl, at which point the electrochemical interference is very low. When a
      washing-free immunosensor is applied to cardiac troponin I detection in human
      serum, the calculated detection limit is approximately 10 pg/mL, indicating that
      the immunosensor is very sensitive in spite of the use of washing-free detection
      with a short detection period (10 min for incubation and 100 s for
      electrochemical measurement). The low-interference washing-free electrochemical
      immunosensor shows good promise for fast and simple point-of-care testing. 

PMID- 25751003
TI  - Densified network glasses and liquids with thermodynamically reversible and
      structurally adaptive behaviour.
AB  - If crystallization can be avoided during cooling, a liquid will display a
      substantial increase of its viscosity, and will form a glass that behaves as a
      solid with a relaxation time that grows exponentially with decreasing
      temperature. Given this 'off-equilibrium' nature, a hysteresis loop appears when
      a cooling/heating cycle is performed across the glass transition. Here we report
      on molecular dynamics simulations of densified glass-forming liquids that follow
      this kind of cycle. Over a finite pressure interval, minuscule thermal changes
      are found, revealing glasses of 'thermally reversible' character with optimal
      volumetric or enthalpic recovery. By analysing the topology of the atomic network
      structure, we find that corresponding liquids adapt under the pressure-induced
      increasing stress by experiencing larger bond-angle excursions. The analysis of
      the dynamic behaviour reveals that the structural relaxation time is
      substantially reduced in these adaptive liquids, and also drives the reversible
      character of the glass transition. Ultimately, the results substantiate the
      notion of stress-free (Maxwell isostatic) rigidity in disordered molecular
      systems, while also revealing new implications for the topological engineering of
      complex materials. 

PMID- 25751002
TI  - Autophagy-independent senescence and genome instability driven by targeted
      telomere dysfunction.
AB  - Telomere dysfunction plays a complex role in tumorigenesis. While dysfunctional
      telomeres can block the proliferation of incipient cancer clones by inducing
      replicative senescence, fusion of dysfunctional telomeres can drive genome
      instability and oncogenic genomic rearrangements. Therefore, it is important to
      define the regulatory pathways that guide these opposing effects. Recent work has
      shown that the autophagy pathway regulates both senescence and genome instability
      in various contexts. Here, we apply models of acute telomere dysfunction to
      determine whether autophagy modulates the resulting genome instability and
      senescence responses. While telomere dysfunction rapidly induces autophagic flux
      in human fibroblast cell lines, inhibition of the autophagy pathway does not have
      a significant impact upon the transition to senescence, in contrast to what has
      previously been reported for oncogene-induced senescence. Our results suggest
      that this difference may be explained by disparities in the development of the
      senescence-associated secretory phenotype. We also show that chromosome fusions
      induced by telomere dysfunction are comparable in autophagy-proficient and
      autophagy-deficient cells. Altogether, our results highlight the complexity of
      the senescence-autophagy interface and indicate that autophagy induction is
      unlikely to play a significant role in telomere dysfunction-driven senescence and
      chromosome fusions. 

PMID- 25751004
TI  - Evaluation of Antibacterial Activity of Lactobacillus Spp. on Selected Food
      Spoilage Bacteria.
AB  - This study was done to isolate Lactobacillus species from curd, amla/Indian
      gooseberry and orange and to assess their antagonistic ability against selected
      food spoilage bacteria, Escherichia coli, Pseudomonas spp. and Bacillus spp.
      isolated from natural food sources. In the approaches used, native Lactobacillus
      spp. were isolated from amla, orange and curd and identified by standard
      microbiological methods. Their antagonistic affect was tested by disc diffusion
      tests against three selected test isolates, Escherichia coli, Pseudomonas and
      Bacillus spp. isolated from tomato, pumpkin, cauliflower, lady's finger, carrot,
      and milk. There are recent patents also suggesting use of novel strains of
      Lactobacillus for microbial antagonism. In our present work, the lactobacilli
      isolated from different food sources showed varied ability to inhibit the growth
      of test isolates. The growth of test isolates was inhibited by Lactobacillus
      isolates with one of the Lactobacillus isolate from amla being the most potent
      inhibitor. 

PMID- 25751005
TI  - Metabolic phenotyping of an adoptive transfer mouse model of experimental colitis
      and impact of dietary fish oil intake.
AB  - Inflammatory bowel diseases are acute and chronic disabling inflammatory
      disorders with multiple complex etiologies that are not well-defined. Chronic
      intestinal inflammation has been linked to an energy-deficient state of gut
      epithelium with alterations in oxidative metabolism. Plasma-, urine-, stool-, and
      liver-specific metabonomic analyses are reported in a naive T cell adoptive
      transfer (AT) experimental model of colitis, which evaluated the impact of long
      chain n-3 polyunsaturated fatty acid (PUFA)-enriched diet. Metabolic profiles of
      AT animals and their controls under chow diet or fish oil supplementation were
      compared to describe the (i) consequences of inflammatory processes and (ii) the
      differential impact of n-3 fatty acids. Inflammation was associated with higher
      glycoprotein levels (related to acute-phase response) and remodeling of PUFAs.
      Low triglyceride levels and enhanced PUFA levels in the liver suggest activation
      of lipolytic pathways that could lead to the observed increase of phospholipids
      in the liver (including plasmalogens and sphingomyelins). In parallel, the
      increase in stool excretion of most amino acids may indicate a protein-losing
      enteropathy. Fecal content of glutamine was lower in AT mice, a feature
      exacerbated under fish oil intervention that may reflect a functional
      relationship between intestinal inflammatory status and glutamine metabolism. The
      decrease in Krebs cycle intermediates in urine (succinate, alpha-ketoglutarate)
      also suggests a reduction in the glutaminolytic pathway at a systemic level. Our
      data indicate that inflammatory status is related to this overall loss of energy
      homeostasis. 

PMID- 25751006
TI  - Nano Traditional Chinese Medicine: Current Progresses and Future Challenges.
AB  - Nano traditional Chinese medicine (nano TCM) refers to bioactive ingredients,
      bioactive parts, medicinal materials or complex prescription, being approximately
      100 nm in size, which are processed by nanotechnology. Nano TCM is a product of
      the TCM modernization, and is an application of nanotechnology in the field of
      TCM. This article reviews literatures on researches of nano TCM, which were
      published in the past 15 years. Different nanotechnologies have been used in
      preparation of Nano TCM in view of the varying aims of the study. The mechanical
      crushing technology is the main approach for nanolization of TCM material and
      complex prescription, and nanoparticulate drug delivery systems is the main
      approach for nanolization of bioactive ingredients or bioactive parts in TCM.
      Nano TCM has a number of advantages, for example, enhancing the bioavailability
      of TCM, reducing the adverse effects of TCM, achieving sustained release,
      attaining targeted delivery, enhancing pharmacological effects and improving the
      administration route of TCM. However, there are still many problems that must be
      resolved in nano TCM research. The main challenges to nano TCM include the theory
      system of TCM modernization, preparation technology, safety and stability, etc. 

PMID- 25751007
TI  - Dormant Circulating Tumor Cells in Prostate Cancer: Therapeutic, Clinical and
      Biological Implications.
AB  - Circulating Tumor Cells (CTCs) are a valuable prognostic factor in several solid
      tumors. By understanding the biological characteristics of CTCs we could better
      understand the biology of metastasis. CTCs usually adopt a dormant state that is
      believed to be a strategy to survive in extreme conditions. To enter a dormant
      state, CTCs undergo numerous phenotypic, genetic and functional mutations that
      significantly affect the efficacy of the therapies used to kill dormant CTCs.
      Hence, understanding the biological events involved in the dormancy process of
      CTCs would allow the identification of new therapeutic targets. Some experimental
      studies or preclinical models have explored these biological events, as well as
      the molecular factors that contribute to the maintenance of and release from
      dormancy. However, few studies have assessed the effects of anticancer therapies
      on dormant cells. This study reviews current the data currently available on cell
      dormancy mechanisms in prostate cancer, with a special focus on the functional,
      genetic and phenotypic plasticity of CTCs and their potential implications in the
      clinical and therapeutic management of prostate cancer. 

PMID- 25751008
TI  - Selective Modulators of alpha5-Containing GABAA Receptors and their Therapeutic
      Significance.
AB  - GABAA receptors containing the alpha5 subunit (5GABAARs) are found mainly in the
      hippocampus where they mediate a tonic chloride leak current and contribute a
      slow component to GABAergic inhibitory synaptic currents. Their inhibitory effect
      on the excitability of hippocampal neurons at least partly explains why changes
      in the level of activity of 5GABAARs affect cognition, learning and memory. These
      receptors have been implicated as potential therapeutic targets for a range of
      clinical conditions including age-related dementia, stroke, schizophrenia, Down
      syndrome and anesthetic- induced amnesia. Accordingly, a range of pharmacological
      modulators that selectively target 5GABAARs, as either inhibitors or allosteric
      enhancers, have been developed. Although many of these compounds show therapeutic
      effects in animal models of the above clinical disorders, none has been marketed
      yet due to unsuccessful clinical trials and toxicity in humans. These experiments
      have also revealed paradoxical effects of 5GABAAR modulation (e.g., cognitive
      impairments can be reversed by both positive and negative modulation), suggesting
      that our knowledge of the physiological roles of 5GABAARs is incomplete. This
      review highlights the various positive and negative modulators for 5GABAARs that
      have been developed, key findings concerning their effects in behavioral studies,
      and their importance across a number of therapeutic fields. It also highlights
      some of the gaps in our knowledge of the physiological and pathological roles of
      alpha5GABAARs. 

PMID- 25751009
TI  - Heterocyclic Scaffolds: Centrality in Anticancer Drug Development.
AB  - Cancer has been cursed for human beings for long time. Millions people lost their
      lives due to cancer. Despite of the several anticancer drugs available, cancer
      cannot be cured; especially at the late stages without showing any side effect.
      Heterocyclic compounds exhibit exciting medicinal properties including
      anticancer. Some market selling heterocyclic anticancer drugs include 5
      flourouracil, methortrexate, doxorubicin, daunorubicin, etc. Besides, some
      natural products such as vinblastine and vincristine are also used as anticancer
      drugs. Overall, heterocyclic moeities have always been core parts in the
      expansion of anticancer drugs. This article describes the importance of
      heterocyclic nuclei in the development of anticancer drugs. Besides, the attempts
      have been made to discuss both naturally occurring and synthetic heterocyclic
      compounds as anticancer agents. In addition, some market selling anticancer
      heterocyclic compounds have been described. Moreover, the efforts have been made
      to discuss the mechanisms of actions and recent advances in heterocyclic
      compounds as anticancer agents. The current challenges and future prospectives of
      heterocyclic compounds have also been discussed. Finally, the suggestions for
      syntheses of effective, selective, fast and human friendly anticancer agents are
      discussed into the different sections. 

PMID- 25751010
TI  - Endogenous Cardioprotective Agents: Role in Pre and Postconditioning.
AB  - Cardiovascular diseases (CVD) are the leading cause of death, chronic illness and
      disability in Western countries. The most common cause of CVD derives from the
      harmful effects of acute myocardial ischemia and subsequent reperfusion injury.
      Cardioprotection against acute ischemia/ reperfusion injury is made possible by
      the "conditioning protocols." Conditioning is obtained by applying a few periods
      of brief ischemia and reperfusion in the event of prolonged (index) ischemia that
      may cause myocardial infarction. Whilst the conditioning stimulus is applied
      before the index ischemia in ischemic pre-conditioning, it is applied after the
      event in post-conditioning. Pre and post- conditioning stimuli can be applied in
      a different/remote organ (remote pre- and post-conditioning); in this case
      conditioning stimulus can also be applied during the index event, in the so
      called remote per-conditioning. All these endogenous cardioprotective strategies
      recruit endogenous cytoprotective agents and factors that elicit specific
      cardioprotective pathways. Here, we discuss many of these cardioprotective
      factors compared to literature and highlight their main characteristics and
      mechanisms of action. Enphasis is given to endogenous cardioprotective agents
      acting or not on surface receptors, including chromogranin A derivatives, ghrelin
      associated peptides, growth factors and cytokines, and to microvesicles and
      exosomes. Moreover the cardioprotective effects of gasotransmitters nitric oxide,
      hydrogen sulphide and carbon monoxide are reviewed. The possible clinical
      translation of these knowledge for future successful therapies is briefly and
      critically discussed. 

PMID- 25751011
TI  - Mini Review: Pathophysiology of Erectile Dysfunction.
AB  - Erectile dysfunction (ED) is a major health problem as the population ages. Basic
      science research for the last two decades has expanded the knowledge on ED and
      identified several key molecular changes associated with the pathogenesis of ED,
      including nitric oxide (NO) / cyclic guanosine monophosphate (cGMP) / protein
      kinase G (PKG) pathway, RhoA/Rho-associated protein kinase (ROCK) signaling
      pathway, reactive oxygen species (ROS), renin-angiotensin system (RAS) and tumor
      necrosis factor-alpha (TNF-alpha). The causes of ED are classified into aging,
      vasculogenic, neurogenic, endocrinological, drug-induced and psychogenic. ED is
      often associated with systemic diseases, such as diabetes and cardiovascular
      diseases. In this review, we will review the molecular mechanisms of ED and known
      mechanisms behind ED associated with systemic diseases.

PMID- 25751012
TI  - Chemical constituents from rhizomes of Cautleya spicata (Sm.) Baker
      (Zingiberaceae).
AB  - The chemical investigation of ethanolic extract from rhizomes of Cautleya spicata
      (Sm.) Baker (Zingiberaceae) has resulted in the isolation of eight compounds
      which were characterised as beta-sitosterol (1), beta-sitosterol beta-D-glucoside
      (2), bergapten (3), zerumin A (4), (E)-labda-8(17),12-diene-15,16-dial (5),
      kaempferol (6), quercetin (7) and astragalin (8). All compounds were identified
      by spectroscopic and chemical methods. This paper describes the first
      phytochemical work on C. spicata. 

PMID- 25751013
TI  - Communication practices and preferences between orthodontists and general
      dentists.
AB  - OBJECTIVE: To evaluate similarities and differences in orthodontists' and general
      dentists' perceptions regarding their interdisciplinary communication. MATERIALS
      AND METHODS: Orthodontists (N  =  137) and general dentists (N  =  144)
      throughout the United States responded to an invitation to participate in a Web
      based and mailed survey, respectively. RESULTS: The results indicated that
      orthodontists communicated with general dentists using the type of media general
      dentists preferred to use. As treatment complexity increased, orthodontists
      shifted from one-way forms of communication (letters) to two-way forms of
      communication (phone calls; P < .05). Both orthodontists and general dentists
      reported that orthodontists' communication regarding white spot lesions was
      inadequate. When treating patients with missing or malformed teeth, orthodontists
      reported that they sought input from the general dentists at a higher rate than
      the general dentists reported (P < .005). CONCLUSIONS: Orthodontists' and general
      dentists' perceptions of how often specific types of media were used for
      interdisciplinary communication were generally similar. They differed, however,
      with regard to how adequately orthodontists communicated with general dentists
      and how often orthodontists sought input from general dentists. The methods and
      extent of communication between orthodontists and general dentists need to be
      determined on a patient-by-patient basis.

PMID- 25751014
TI  - Levels of gingival crevicular fluid matrix metalloproteinases in periodontally
      compromised teeth under orthodontic forces.
AB  - OBJECTIVE: To examine levels of matrix metalloproteinases (MMPs)-1, -2, -3, -7, 
      8, -12, and -13 in the gingival crevicular fluid (GCF) of periodontally
      compromised teeth at different time points during orthodontic movement. MATERIALS
      AND METHODS: Ten controlled periodontitis subjects were submitted to orthodontic
      treatment. One dental arch was subjected to orthodontic movement, and teeth in
      the opposite arch were used as controls. GCF samples were collected from the
      lingual sites of two movement and two control incisors 1 week before orthodontic
      activation (-7 d), immediately after orthodontic activation, and after 1 hour, 24
      hours, and 7, 14, and 21 days. Multiplexed bead immunoassay was used to measure
      MMPs in GCF. Data were analyzed using Friedman and Wilcoxon statistical tests.
      RESULTS: The only significant change found over time was in the levels of MMP-1
      in the movement group (P < .05). When the two groups were compared after
      activation, the only statistically significant difference found was in levels of
      MMP-12 24 hours after activation (P < .05). CONCLUSIONS: Our findings suggested
      that the orthodontic movement of periodontally compromised teeth without active
      pockets did not result in significant changes in the GCF levels of MMPs.

PMID- 25751015
TI  - Transient IL-10 receptor blockade can enhance CD8(+) T cell responses to a simian
      adenovirus-vectored HIV-1 conserved region immunogen.
AB  - Viral vector vaccines designed to elicit CD8(+) T cells in non-human primates
      exert potent control of immunodeficiency virus infections; however, similar
      approaches have been unsuccessful in humans. Adenoviral vectors elicit potent T
      cell responses but also induce production of immunosuppressive interleukin-10 (IL
      10), which can limit the expansion of T cell responses. We investigated whether
      inhibiting IL-10 signaling prior to immunization with a candidate adenovirus
      vectored-HIV-1 vaccine, ChAdV63.HIVconsv, could modulate innate and adaptive
      immune responses in BALB/c mice. Transient IL-10 receptor blockade led to a
      modest but significant increase in the total magnitude CD8(+) T cell response to
      HIVconsv, but did not affect T cell responses to immunodominant epitopes. Anti-IL
      10R-treated animals also exhibited greater expression of CD86 on CD11c(+)
      dendritic cells. Our data support further investigation and optimization of IL-10
      blocking strategies to improve the immunogenicity of vaccines based on
      replication-defective adenoviruses. 

PMID- 25751016
TI  - Dynamics based pharmacophore models for screening potential inhibitors of
      mycobacterial cyclopropane synthase.
AB  - The therapeutic challenges in the treatment of tuberculosis demand
      multidisciplinary approaches for the identification of potential drug targets as
      well as fast and accurate techniques to screen huge chemical libraries.
      Mycobacterial cyclopropane synthase (CmaA1) has been shown to be essential for
      the survival of the bacteria due to its critical role in the synthesis of mycolic
      acids. The present study proposes pharmacophore models based on the structure of
      CmaA1 taking into account its various states in the cyclopropanation process, and
      their dynamic nature as assessed using molecular dynamics (MD) simulations. The
      qualities of these pharmacophore models were validated by mapping 23 molecules
      that have been previously reported to exhibit inhibitory activities on CmaA1.
      Additionally, 1398 compounds that have been shown to be inactive for tuberculosis
      were collected from the ChEMBL database and were screened against the models for
      validation. The models were further validated by comparing the results from
      pharmacophore mapping with the results obtained from docking these molecules with
      the respective protein structures. The best models are suggested by validating
      all the models based on their screening abilities and by comparing with docking
      results. The models generated from the MD trajectories were found to perform
      better than the one generated based on the crystal structure demonstrating the
      importance of incorporating receptor flexibility in drug design. 

PMID- 25751017
TI  - Dislocations in SrTiO3: easy to reduce but not so fast for oxygen transport.
AB  - The effect of dislocations on the chemical, electrical and transport properties
      in oxide materials is important for electrochemical devices, such as fuel cells
      and resistive switches, but these effects have remained largely unexplored at the
      atomic level. In this work, by using large-scale atomistic simulations, we
      uncover how a ?100?{011} edge dislocation in SrTiO3, a prototypical perovskite
      oxide, impacts the local defect chemistry and oxide ion transport. We find that,
      in the dilute limit, oxygen vacancy formation energy in SrTiO3 is lower at sites
      close to the dislocation core, by as much as 2 eV compared to that in the bulk.
      We show that the formation of a space-charge zone based on the redistribution of
      charged oxygen vacancies can be captured quantitatively at atomistic level by
      mapping the vacancy formation energies around the dislocation. Oxide-ion
      diffusion was studied for a low vacancy concentration regime (ppm level) and a
      high vacancy concentration regime (up to 2.5%). In both cases, no evidence of
      pipe-diffusion, i.e., significantly enhanced mobility of oxide ions, was found as
      determined from the calculated migration barriers, contrary to the case in
      metals. However, in the low vacancy concentration regime, the vacancy
      accumulation at the dislocation core gives rise to a higher diffusion
      coefficient, even though the oxide-ion mobility itself is lower than that in the
      bulk. Our findings have important implications for applications of perovskite
      oxides for information and energy technologies. The observed lower oxygen vacancy
      formation energy at the dislocation core provides a quantitative and direct
      explanation for the electronic conductivity of dislocations in SrTiO3 and related
      oxides studied for red-ox based resistive switching. Reducibility and electronic
      transport at dislocations can also be quantitatively engineered into active
      materials for fuel cells, catalysis, and electronics. 

PMID- 25751018
TI  - The work life and career development of young breast cancer survivors.
AB  - Breast cancer survivors represent the largest proportion of cancer survivors, and
      the rate of young breast cancer survivors who are diagnosed before the age of 40
      is increasing. Cancer survivorship scholarship has begun to address many aspects
      of survivors' quality of life, yet the role of work and career issues have been
      understudied, particularly for young survivors. To explore the work lives and
      career development of young breast cancer survivors, this study used consensual
      qualitative research methodology (Hill, Thompson, & Williams, 1997) to analyze
      data from qualitative interviews with 13 young women diagnosed with breast cancer
      before the age of 40. The 4 career-related domains that emerged from the data
      were (a) cancer-related work challenges, (b) coping with cancer-related work
      challenges, (c) reappraisal of career development after cancer, and (d)
      components of career and life satisfaction after cancer. Experiencing breast
      cancer at a young age was viewed by participants as contributing to an increased
      desire for work to provide a sense of meaning as well as financial security and
      insurance. Cancer was further viewed as contributing to lost control over career
      success and work choices, treatment side effects that interfere with work self
      efficacy and capabilities, and interpersonal difficulties connecting within and
      outside of work. Women with more extensive cancer treatment and side effects
      reported greater work struggles. Despite this, participants' cancer narratives
      were characterized by a range of coping strategies, including reframing and
      seeking control, and by evidence of persistence, resilience, and hope.
      Implications for research and practice are discussed.

PMID- 25751019
TI  - Does measuring body weight impact subsequent response to eating behavior
      questions?
AB  - OBJECTIVES: If being weighed impacts perceptions of eating behavior, it is
      important that the order of questionnaires and weighing be considered in research
      and practice. A quasi-experimental study was performed to examine whether being
      weighed immediately prior to completing a questionnaire affects responses to
      eating behavior questions. It was hypothesized that being weighed would serve as
      a priming stimulus and increase measures of dietary restraint, disinhibition, and
      hunger. METHODS: Trained researchers collected a sample of volunteers (n = 355)
      in 8 locations in the United States on two Saturdays in the summer of 2011. Half
      of the participants were weighed immediately prior to completing the Three Factor
      Eating Questionnaire (TFEQ), with the remaining half weighed immediately after
      TFEQ completion. RESULTS: A priori hypotheses were not supported despite
      replicating known relationships between weight, dietary restraint and
      disinhibition. Results indicated that being weighed first produced a difference
      in differences on disinhibition scores between low restraint score (95% CI = 4.65
      6.02) and high restraint score (95% CI = 6.11-7.57) compared to being weighed
      after questionnaire completion (p = 0.003). However, this relationship was not
      significant when modeling restraint as a continuous variable, questioning the use
      of dichotomization. CONCLUSIONS: Being weighed is unlikely to be a strong enough
      prime to significantly change scores on eating behavior questionnaires for
      everyone, but may allow differences in restraint status to become more evident.
      Researchers assessing dietary restraint should be wary of the possibility of
      producing different results when treating restraint as continuous or dichotomous,
      which could lead to different interpretations.

PMID- 25751020
TI  - Shape-switching microrobots for medical applications: the influence of shape in
      drug delivery and locomotion.
AB  - The effect of dynamic shape switching of hydrogel bilayers on the performance of
      self-folding microrobots is investigated for navigation in body orifices and drug
      release on demand. Tubular microrobots are fabricated by coupling a
      thermoresponsive hydrogel nanocomposite with a poly(ethylene glycol)diacrylate
      (PEGDA) layer, to achieve spontaneous and reversible folding from a planar
      rectangular structure. Graphene oxide (GO) or silica-coated superparamagnetic
      iron oxide nanoparticles are dispersed in the thermoresponsive hydrogel matrix to
      provide near-infrared (NIR) light sensitivity or magnetic actuation,
      respectively. The NIR light-responsive microstructures are fabricated for
      triggered drug delivery while magnetic nanocomposite-based microrobots are used
      to analyze the role of shape in locomotion. Experimental analysis and
      computational simulations of tubular structures show that drug release and
      motility can be optimized through controlled shape change. These concepts are
      finally applied to helical microrobots to show a possible way to achieve
      autonomous behavior. 

PMID- 25751022
TI  - Theoretical study on structures and bond properties of NpO2(m+) ions and
      NpO2(H2O)n(m+) (m = 1-2, n = 1-6) complexes in the gas phase and aqueous
      solution.
AB  - The equilibrium structures, vibrational frequencies, and bond characteristics of
      NpO2(m+) ions and NpO2(H2O)n(m+) (m = 1-2, n = 1-6) complexes have been studied
      by carrying out ab initio calculations in the gas phase and aqueous solution. The
      geometries have been obtained at the B3LYP level with the use of the polarized
      continuum model (PCM). The computed structural parameters that are in reasonably
      good agreement with the available data show that the solvation effect leads to a
      red shift of the IR spectra and the weakness of interaction strengths in neptunyl
      ions. By comparing the structural properties and the density of states (DOS) of
      these aqua complexes in the gas phase and aqueous solution, it is found that the
      solvation effect can be simulated approximately with the calculations of these
      aqua complexes in the gas phase. In addition, the DOS of these aqua complexes
      together with the binding energies between the neptunyl ion and water molecule
      reveal that the penta-aqua complex is preferred for neptunyl ions in aqueous
      solution.

PMID- 25751021
TI  - MtDNA mutagenesis impairs elimination of mitochondria during erythroid maturation
      leading to enhanced erythrocyte destruction.
AB  - Haematopoietic progenitor cells show special sensitivity to mitochondrial DNA
      (mtDNA) mutagenesis, which suggests that increased mtDNA mutagenesis could
      underlie anemias. Here we show that elevated mtDNA mutagenesis in mice with a
      proof-reading deficient mtDNA polymerase (PolG) leads to incomplete mitochondrial
      clearance, with asynchronized iron loading in erythroid precursors, and increased
      total and free cellular iron content. The resulting Fenton chemistry leads to
      oxidative damage and premature destruction of erythrocytes by splenic
      macrophages. Our data indicate that mitochondria actively contribute to their own
      elimination in reticulocytes and modulate iron loading. Asynchrony of this
      sequence of events causes severe mitochondrial anaemia by depleting the organism
      of red blood cells and the bone marrow of iron. Our findings account for the
      anaemia development in a progeroid mouse model and may have direct relevance to
      the anemias associated with human mitochondrial disease and ageing. 

PMID- 25751023
TI  - Physical activity and social support in adolescents: analysis of different types
      and sources of social support.
AB  - Little is known about the influence of different types and sources of social
      support on physical activity in adolescents. The aim of this study was to analyse
      the association between physical activity and different types and sources of
      social support in adolescents. The sample consisted of 2,859 adolescents between
      14-19 years of age in the city of Joao Pessoa, in Northeastern Brazil. Physical
      activity was measured with a questionnaire and social support from parents and
      friends using a 10-item scale five for each group (type of support:
      encouragement, joint participation, watching, inviting, positive comments and
      transportation). Multivariable analysis showed that the types of support provided
      by parents associated with physical activity in adolescents were encouragement
      for females (P < 0.001) and adolescents between 14-16 years of age (P = 0.003),
      and transportation (P = 0.014) and comments (P = 0.037) for males. The types of
      social support provided by friends were: joint participation in male adolescents
      (P < 0.001) and in these 17-19-year-olds (P < 0.001), and comments in both
      genders (males: P = 0.009; females: P < 0.001) and 14-16-year-olds (P < 0.001).
      We conclude that the type of social support associated with physical activity
      varies according to its source, as well as the gender and age of the adolescents.

PMID- 25751024
TI  - Controlled cyclic compression of an open tibial fracture using an external
      fixator affects fracture healing in mice.
AB  - Fractures resulting in impaired healing can be treated with mechanical
      stimulation via external fixators. To examine the effect of mechanical
      stimulation on fracture healing, we developed an external fixator for use in a
      mouse model. A 0.5 mm tibial osteotomy was stabilized with the external fixator
      in C57BL/6 mice. Osteotomies in the treatment group (nt = 41) were subjected to
      daily sessions of 150 MUm of controlled displacement with the aim to create a
      more mineralized callus at 21 days compared with the control group (nc = 39).
      Qualitative assessment of the histology found no notable difference in healing
      patterns between groups at 7, 12, 17, and 21 days. At 21 days, micro-computed
      tomography (CT) analysis showed that the control group had a significantly higher
      bone volume (BV) fraction and trabecular number compared with treatment; however
      there was no significant difference in the total volume (TV) of the callus or
      trabecular thickness between groups. In summary, the external fixator was used
      with a motion application system to apply controlled displacement to a healing
      fracture; however, this treatment did not result in a more mineralized callus at
      21 days. 

PMID- 25751025
TI  - Factorial Invariance of the Physical Activity Neighborhood Environment Survey
      Among Single- Versus Multi-Family Housing Residents.
AB  - PURPOSE: Individual perceptions of one's neighborhood environment influence
      decisions about physical activity participation. Differences between single
      family housing neighborhoods versus multi-family housing neighborhoods may affect
      perceptions and lead to varying responses on surveys designed to assess
      perceptions of the neighborhood environment for physical activity. This study
      tested the factorial invariance for the Physical Activity Neighborhood
      Environment Survey (PANES) between residents of single-family versus multi-family
      housing neighborhoods. METHOD: This study was a secondary data analysis of PANES
      ratings from African American and Hispanic or Latina women (n = 324) who
      participated in the Health Is Power study (NCI R01CA109403), a multi-site,
      community-based trial to investigate the relationship between neighborhood
      factors and physical activity adoption and maintenance. Factorial invariance was
      tested using a series of nested confirmatory factor analysis models. RESULTS: The
      final model was a 2nd-order factor structure with partial invariance of item
      intercepts. The 2nd-order factor structure and the relationships of the PANES
      items to the 1st-order factors (amenable, unsafe, and walkable) and of the 1st
      order factors to the 2nd-order factor (environment) were invariant between the
      single-family and multi-family housing neighborhood groups. CONCLUSION: These
      findings support the construct validity of PANES, which can be considered valid
      for measuring neighborhood perceptions among residents of neighborhoods with
      different housing types.

PMID- 25751026
TI  - Quantitative optical coherence tomography imaging of intermediate flow defect
      phenotypes in ciliary physiology and pathophysiology.
AB  - Cilia-driven fluid flow is a critical yet poorly understood aspect of pulmonary
      physiology. Here, we demonstrate that optical coherence tomography-based particle
      tracking velocimetry can be used to quantify subtle variability in cilia-driven
      flow performance in Xenopus, an important animal model of ciliary biology.
      Changes in flow performance were quantified in the setting of normal development,
      as well as in response to three types of perturbations: mechanical (increased
      fluid viscosity), pharmacological (disrupted serotonin signaling), and genetic
      (diminished ciliary motor protein expression). Of note, we demonstrate decreased
      flow secondary to gene knockdown of kif3a, a protein involved in ciliogenesis, as
      well as a dose-response decrease in flow secondary to knockdown of dnah9, an
      important ciliary motor protein.

PMID- 25751027
TI  - Two-stage multi-Gaussian fitting of conduit artery photoplethysmography waveform
      during induced unilateral hemodynamic events.
AB  - Photoplethysmography (PPG) is an optical technique with high diagnostic
      potential, yet clinical applications remain underdeveloped. Standardization of
      signal recording and quantification of waveform are essential prerequisites for
      broader clinical use. The aim of this study was to utilize a two-stage multi
      Gaussian fitting technique in order to examine the parameters of conduit artery
      PPG waveform recorded during increasing the unilateral regional vascular
      resistance (RVR). This study was conducted on 14 young and healthy volunteers;
      various external compressions (ECs) were performed by inflating a tight cuff at
      0, 40, 80, and 200 mmHg, while registering femoral PPG (wavelength 880 nm),
      diameter, blood flow linear velocity (vascular ultrasound), and the arterial
      pressure (Finapres) during the states of the baseline, partial, and total
      arterial occlusion, and resultant reactive hyperemia. An increase of the EC
      elevated the arterial stiffness (AS) and the unilateral distal RVR, and caused a
      shift of the fitted multi-Gaussian parameters: a decreased delay between
      reflected and traverse wave components and an increased ratio of their
      amplitudes. It was concluded that two-stage multi-Gaussian waveform
      quantification demonstrates an approach potentially extending the use of arterial
      site PPG in the assessment of diagnostically useful markers e.g., the RVR and the
      AS.

PMID- 25751028
TI  - Modeling changes in the hemoglobin concentration of skin with total diffuse
      reflectance spectroscopy.
AB  - The ability to monitor changes in the concentration of hemoglobin in the blood of
      the skin in real time is a key component to personalized patient care. Since
      hemoglobin has a unique absorption spectrum in the visible light range, diffuse
      reflectance spectroscopy is the most common approach. Although the collection of
      the diffuse reflectance spectrum with an integrating sphere (IS) has several
      calibration challenges, this collection method is sufficiently user-friendly that
      it may be worth overcoming the initial difficulty. Once the spectrum is obtained,
      it is commonly interpreted with a log-inverse-reflectance (LIR) or "absorbance"
      analysis that can only accurately monitor changes in the hemoglobin concentration
      when there are no changes to the nonhemoglobin chromophore concentrations which
      is not always the case. We address the difficulties associated with collection of
      the diffuse reflectance spectrum with an IS and propose a model capable of
      retrieving relative changes in hemoglobin concentration from the visible light
      spectrum. The model is capable of accounting for concentration changes in the
      nonhemoglobin chromophores and is first characterized with theoretical spectra
      and liquid phantoms. The model is then used in comparison with a common LIR
      analysis on temporal measurements from blanched and reddened human skin.

PMID- 25751029
TI  - Quantitative study on appearance of microvessels in spectral endoscopic imaging.
AB  - Increase in abnormal microvessels in the superficial mucosa is often relevant to
      diagnostic findings of neoplasia in digestive endoscopy; hence, observation of
      superficial vasculature is crucial for cancer diagnosis. To enhance the
      appearance of such vessels, several spectral endoscopic imaging techniques have
      been developed, such as narrow-band imaging and blue laser imaging. Both
      techniques exploit narrow-band blue light for the enhancement. The emergence of
      such spectral imaging techniques has increased the importance of understanding
      the relation of the light wavelength to the appearance of superficial
      vasculature, and thus a new method is desired for quantitative analysis of vessel
      visibility in relation to the actual structure in the tissue. Here, we developed
      microvessel-simulating phantoms that allowed quantitative evaluation of the
      appearance of 15-MUm-thick vessels. We investigated the relation between the
      vascular contrast and light wavelength by the phantom measurements and also
      verified it in experiments with swine, where the endoscopically observed vascular
      contrast was investigated together with its real vascular depth and diameter
      obtained by microscopic observation of fluorescence-labeled vessels. Our study
      indicates that changing the spectral property even in the wavelength range of
      blue light may allow selective enhancement of the vascular depth for clinical
      use.

PMID- 25751030
TI  - Detection of canine skin and subcutaneous tumors by visible and near-infrared
      diffuse reflectance spectroscopy.
AB  - Cancer is the main cause of canine morbidity and mortality. The existing
      evaluation of tumors requires an experienced veterinarian and usually includes
      invasive procedures (e.g., fine-needle aspiration) that can be unpleasant for the
      dog and the owner. We investigate visible and near-infrared diffuse reflectance
      spectroscopy (DRS) as a noninvasive optical technique for evaluation and
      detection of canine skin and subcutaneous tumors ex vivo and in vivo. The optical
      properties of tumors and skin were calculated in a spectrally constrained manner,
      using a lookup table-based inverse model. The obtained optical properties were
      analyzed and compared among different tumor groups. The calculated parameters of
      the absorption and reduced scattering coefficients were subsequently used for
      detection of malignant skin and subcutaneous tumors. The detection sensitivity
      and specificity of malignant tumors ex vivo were 90.0% and 73.5%, respectively,
      while corresponding detection sensitivity and specificity of malignant tumors in
      vivo were 88.4% and 54.6%, respectively. The obtained results show that the DRS
      is a promising noninvasive optical technique for detection and classification of
      malignant and benign canine skin and subcutaneous tumors. The method should be
      further investigated on tumors with common origin.

PMID- 25751031
TI  - Improvement in obstructive sleep apnea diagnosis and management wait times: A
      retrospective analysis of home management pathway for obstructive sleep apnea.
AB  - Obstructive sleep apnea is a common condition within the Canadian population. The
      current gold standard for diagnosis and management of patients is in-laboratory
      (in-lab) polysomnography; however, the limited availability of testing options
      for patients has led to long wait times and increased disease burden within the
      population. The Sleep Research Laboratory in Saskatoon (Saskatchewan) implemented
      a home management program to run in parallel with the in-lab system several years
      ago in an effort to increase their capacity and reduce wait times. The present
      study was a retrospective analysis of all patients referred to the program
      between 2009 and 2012. The home management system has improved wait times by
      diagnosing and managing up to one-half of the referred patient population,
      reducing the wait for in-lab treatment from a median of 152 days in 2009 to 92
      days in 2012 (P<0.0001). Moving forward, home management can provide a viable
      alternative to in-lab testing for patients who meet strict entry criteria,
      reducing the in-lab workload and, ultimately, reducing wait times. 

PMID- 25751032
TI  - An electrochemical aptasensor based on a TiO2/three-dimensional reduced graphene
      oxide/PPy nanocomposite for the sensitive detection of lysozyme.
AB  - A sensitive aptasensor based on a nanocomposite of hollow titanium dioxide
      nanoball, three-dimensional reduced graphene oxide, and polypyrrole (TiO2/3D
      rGO/PPy) was developed for lysozyme detection. A lysozyme aptamer was easily
      immobilized onto the TiO2/3D-rGO/PPy nanocomposite matrix by assembling the
      aptamer onto graphene through simple pi-stacking interactions and electrostatic
      interactions between PPy molecular chains and aptamer strands. In the presence of
      lysozyme, the aptamer on the adsorbent layer catches the target on the electrode
      interface, which generates a barrier for electrons and inhibits electron
      transfer, subsequently resulting in decreased electrochemically differential
      pulse voltammetric signals of a gold electrode modified with TiO2/3D-rGO/PPy.
      Using this strategy, a low limit of detection of 0.085 ng mL(-1) (5.5 pM) for
      detecting lysozyme was observed within the detection range of 0.1-50 ng mL(-1)
      (0.007-3.5 nM). The aptasensor also presents high specificity for lysozyme, which
      is unaffected by the coexistence of other proteins. Such an aptasensor opens a
      rapid, selective, and sensitive route to lysozyme detection. This finding
      indicates that the TiO2/3D-rGO/PPy nanocomposite could be used as an
      electrochemical biosensor for detecting proteins in the biomedical field. 

PMID- 25751033
TI  - Cerebrospinal fluid vascular endothelial growth factor.

PMID- 25751034
TI  - A case of possible pacemaker undersensing.

PMID- 25751037
TI  - The other-race effect in perception and recognition: insights from the complete
      composite task.
AB  - People are more accurate at recognizing faces of their own race than faces from
      other races, a phenomenon known as the other-race effect. Other-race effects have
      also been reported in some perceptual tasks. Across 3 experiments, White and
      Chinese participants completed recognition tests as well as the complete paradigm
      of the composite task, which measures participants' abilities to selectively
      attend to the target region of a face while ignoring the task-irrelevant region
      of the face. Each task was completed with both own- and other-race faces. At a
      group level, participants showed significant own-race effects in recognition, but
      not in the composite task. At an individual difference level, the results
      provided no support for the hypothesis that a deficit in holistic processing for
      other-race faces drives the other-race effect in recognition. We therefore
      conclude that the other-race effect in recognition is not driven by the processes
      that underpin the composite effect.

PMID- 25751035
TI  - Four RNA families with functional transient structures.
AB  - Protein-coding and non-coding RNA transcripts perform a wide variety of cellular
      functions in diverse organisms. Several of their functional roles are expressed
      and modulated via RNA structure. A given transcript, however, can have more than
      a single functional RNA structure throughout its life, a fact which has been
      previously overlooked. Transient RNA structures, for example, are only present
      during specific time intervals and cellular conditions. We here introduce four
      RNA families with transient RNA structures that play distinct and diverse
      functional roles. Moreover, we show that these transient RNA structures are
      structurally well-defined and evolutionarily conserved. Since Rfam annotates one
      structure for each family, there is either no annotation for these transient
      structures or no such family. Thus, our alignments either significantly update
      and extend the existing Rfam families or introduce a new RNA family to Rfam. For
      each of the four RNA families, we compile a multiple-sequence alignment based on
      experimentally verified transient and dominant (dominant in terms of either the
      thermodynamic stability and/or attention received so far) RNA secondary
      structures using a combination of automated search via covariance model and
      manual curation. The first alignment is the Trp operon leader which regulates the
      operon transcription in response to tryptophan abundance through alternative
      structures. The second alignment is the HDV ribozyme which we extend to the 5'
      flanking sequence. This flanking sequence is involved in the regulation of the
      transcript's self-cleavage activity. The third alignment is the 5' UTR of the
      maturation protein from Levivirus which contains a transient structure that
      temporarily postpones the formation of the final inhibitory structure to allow
      translation of maturation protein. The fourth and last alignment is the SAM
      riboswitch which regulates the downstream gene expression by assuming alternative
      structures upon binding of SAM. All transient and dominant structures are mapped
      to our new alignments introduced here. 

PMID- 25751036
TI  - Self-organized complementary joint action: Behavioral dynamics of an
      interpersonal collision-avoidance task.
AB  - Understanding stable patterns of interpersonal movement coordination is essential
      to understanding successful social interaction and activity (i.e., joint action).
      Previous research investigating such coordination has primarily focused on the
      synchronization of simple rhythmic movements (e.g., finger/forearm oscillations
      or pendulum swinging). Very few studies, however, have explored the stable
      patterns of coordination that emerge during task-directed complementary
      coordination tasks. Thus, the aim of the current study was to investigate and
      model the behavioral dynamics of a complementary collision-avoidance task.
      Participant pairs performed a repetitive targeting task in which they moved
      computer stimuli back and forth between sets of target locations without
      colliding into each other. The results revealed that pairs quickly converged onto
      a stable, asymmetric pattern of movement coordination that reflected differential
      control across participants, with 1 participant adopting a more straight-line
      movement trajectory between targets, and the other participant adopting a more
      elliptical trajectory between targets. This asymmetric movement pattern was also
      characterized by a phase lag between participants and was essential to task
      success. Coupling directionality analysis and dynamical modeling revealed that
      this dynamic regime was due to participant-specific differences in the coupling
      functions that defined the task-dynamics of participant pairs. Collectively, the
      current findings provide evidence that the dynamical coordination processes
      previously identified to underlie simple motor synchronization can also support
      more complex, goal-directed, joint action behavior, and can participate the
      spontaneous emergence of complementary joint action roles.

PMID- 25751038
TI  - Auditory attention is divisible: segregated tone streams can be tracked
      simultaneously.
AB  - Can auditory attention be split? We addressed this question using rapid sequences
      of tones alternating in frequency between 2 remote registers. In these rapid
      sequences, consecutive tones could not be perceptually linked; the tones were
      instead inevitably segregated into 2 concurrent melodic streams. Listeners had to
      determine if the 2 melodies interleaved in a sequence were exact transpositions
      of each other or not. This task could be performed successfully. More crucially,
      performance was better when each component tone of 1 melody was immediately
      transposed in the other melody than when component i of 1 melody was a
      transposition of component i-1 of the other melody. Nevertheless, because the
      melodies were segregated, listeners were unable to determine which was the
      leading melody when 2 interleaved melodies were immediate transpositions of each
      other. Our results are inconsistent with the hypothesis that listeners compared
      concurrent melodic streams using a memory-based serial-processing strategy. It
      instead appears that listeners were able to track such streams in parallel.
      Therefore, attention can be split between concurrent sensory streams even when
      the physical entities making up these streams do not overlap in time.

PMID- 25751039
TI  - Malleable temporal integration of positional information for moving objects.
AB  - One of the primary functions of visual processing is to generate a spatial
      mapping of our immediate vicinity, in order to facilitate interaction. As yet it
      is unclear how this is achieved, but the process likely involves an accrual of
      information over time--a temporal integration of positional information (Eagleman
      & Sejnowski, 2000; Krekelberg et al., 2000). Temporal integration is a common
      computational process evident in diverse settings, such as electrical engineering
      (Bryson & Ho, 1975) and neural coding (Rao, Eagleman & Sejnowski, 2001; Usher &
      McClelland, 2001). In the later context it is sometimes assumed that integration
      dynamics are immobile, and consequently that they can be diagnostic of a sensory
      system (Arnold & Lipp, 2011; Krauskopf & Mollon, 1971; Snowden & Braddick, 1991).
      Other data suggest that integration times can be flexible, varying in concert
      with the properties of a stimulus (Bair & Movshon, 2004) or environment (Ossmy et
      al., 2013). Our data provide behavioral support for malleable integration times.
      We examine a motion-induced illusion of perceived position linked to temporal
      integration, and use prolonged exposure to motion of different speeds (sensory
      adaptation) to modulate the dynamics of neural activity. Results show that
      perceived position is governed by a weighted average of positional estimates from
      multiple channels with distinct, fixed integration times. Postadaptation channel
      contributions are reweighted, resulting in coding that is optimized to the
      dynamics of the prevailing environment.

PMID- 25751040
TI  - Acoustic source characteristics, across-formant integration, and speech
      intelligibility under competitive conditions.
AB  - An important aspect of speech perception is the ability to group or select
      formants using cues in the acoustic source characteristics--for example,
      fundamental frequency (F0) differences between formants promote their
      segregation. This study explored the role of more radical differences in source
      characteristics. Three-formant (F1+F2+F3) synthetic speech analogues were derived
      from natural sentences. In Experiment 1, F1+F3 were generated by passing a
      harmonic glottal source (F0 = 140 Hz) through second-order resonators (H1+H3); in
      Experiment 2, F1+F3 were tonal (sine-wave) analogues (T1+T3). F2 could take
      either form (H2 or T2). In some conditions, the target formants were presented
      alone, either monaurally or dichotically (left ear = F1+F3; right ear = F2). In
      others, they were accompanied by a competitor for F2 (F1+F2C+F3; F2), which
      listeners must reject to optimize recognition. Competitors (H2C or T2C) were
      created using the time-reversed frequency and amplitude contours of F2. Dichotic
      presentation of F2 and F2C ensured that the impact of the competitor arose
      primarily through informational masking. In the absence of F2C, the effect of a
      source mismatch between F1+F3 and F2 was relatively modest. When F2C was present,
      intelligibility was lowest when F2 was tonal and F2C was harmonic, irrespective
      of which type matched F1+F3. This finding suggests that source type and context,
      rather than similarity, govern the phonetic contribution of a formant. It is
      proposed that wideband harmonic analogues are more effective informational
      maskers than narrowband tonal analogues, and so become dominant in across
      frequency integration of phonetic information when placed in competition.

PMID- 25751041
TI  - Opposing effects of semantic diversity in lexical and semantic relatedness
      decisions.
AB  - Semantic ambiguity has often been divided into 2 forms: homonymy, referring to
      words with 2 unrelated interpretations (e.g., bark), and polysemy, referring to
      words associated with a number of varying but semantically linked uses (e.g.,
      twist). Typically, polysemous words are thought of as having a fixed number of
      discrete definitions, or "senses," with each use of the word corresponding to one
      of its senses. In this study, we investigated an alternative conception of
      polysemy, based on the idea that polysemous variation in meaning is a continuous,
      graded phenomenon that occurs as a function of contextual variation in word
      usage. We quantified this contextual variation using semantic diversity (SemD), a
      corpus-based measure of the degree to which a particular word is used in a
      diverse set of linguistic contexts. In line with other approaches to polysemy, we
      found a reaction time (RT) advantage for high SemD words in lexical decision,
      which occurred for words of both high and low imageability. When participants
      made semantic relatedness decisions to word pairs, however, responses were slower
      to high SemD pairs, irrespective of whether these were related or unrelated.
      Again, this result emerged irrespective of the imageability of the word. The
      latter result diverges from previous findings using homonyms, in which ambiguity
      effects have only been found for related word pairs. We argue that participants
      were slower to respond to high SemD words because their high contextual
      variability resulted in noisy, underspecified semantic representations that were
      more difficult to compare with one another. We demonstrated this principle in a
      connectionist computational model that was trained to activate distributed
      semantic representations from orthographic inputs. Greater variability in the
      orthography-to-semantic mappings of high SemD words resulted in a lower degree of
      similarity for related pairs of this type. At the same time, the representations
      of high SemD unrelated pairs were less distinct from one another. In addition,
      the model demonstrated more rapid semantic activation for high SemD words,
      thought to underpin the processing advantage in lexical decision. These results
      support the view that polysemous variation in word meaning can be conceptualized
      in terms of graded variation in distributed semantic representations.

PMID- 25751042
TI  - Older and younger adults' strategies in sensorimotor tasks: insights from Fitts'
      pointing task.
AB  - We investigated how young and older adults differ in sensorimotor tasks. Two
      groups of participants (young and older adults) performed discrete Fitts' tasks
      in which 4 levels of difficulty (ID) were used, resulting from either the
      manipulation of the size of the target (ID(W)) or of the distance between home
      and target positions (ID(D)). Kinematic analysis allowed distinguishing 4
      different types of strategies used to reach the target, on the basis of the
      existence and the nature of submovements. Results showed that the repertoire of
      strategies was significantly smaller in older than in young participants. In
      addition, the frequency of use of the different strategies varied with
      participants' age. Specifically, the most frequent strategies used by older
      participants included submovements, while those used by young participants did
      not include submovements. The differences observed between young and older adults
      were independent of whether ID was manipulated via target size or movement
      distance. Finally, age-related differences in strategy performance were found.
      These results have important implications for furthering our understanding of
      aging effects in sensorimotor tasks. They also illustrate the usefulness of a
      strategy approach in a domain where it had never been formally used before.

PMID- 25751043
TI  - Are arthropods at the heart of virus evolution?
AB  - The huge diversity of negative-sense RNA viruses in insects, spiders and other
      arthropods suggests that these animals could be central to virus origin and
      evolution. 

PMID- 25751044
TI  - What a difference your e-mail makes: effects of informal e-mail addresses in
      online resume screening.
AB  - Resumes are screened rapidly, with some reports stating that recruiters form
      their impressions within 10 seconds. Certain resume characteristics can have a
      significant impact on the snap judgments these recruiters make. The main goal of
      the present study was to examine the effect of the e-mail address (formal vs.
      informal) used in a resume on the hirability perceptions formed by professional
      recruiters (N=73). In addition, the effect of the e-mail address on hirability
      perceptions was compared to the effects of spelling errors and typeface.
      Participants assessed the cognitive ability, personality, and the hirability of
      six fictitious applicants for the job of an HR specialist. The hirability ratings
      for the resumes with informal e-mail addresses were significantly lower than the
      hirability ratings for resumes that featured a formal e-mail address. The effect
      of e-mail address was as strong as the effect of spelling errors and stronger
      than that of typeface. The effect of e-mail address on hirability was mediated by
      perceptions of conscientiousness and honesty-humility. This study among actual
      recruiters shows for the first time that the choice of the e-mail address used on
      a resume might make a real difference. 

PMID- 25751045
TI  - Put on a smiley face: textspeak and personality perceptions.
AB  - With the emergence of Web 2.0, there has been a dramatic surge in user-generated
      content. Although the Internet provides greater freedom in self-presentation,
      computer-mediated communication is characterized by a more relaxed attitude to
      grammar, spelling, and punctuation. The language of the Internet, or textspeak,
      may be suitable for casual interactions but inappropriate in professional
      contexts. Participant perceptions of an author's personality were tested in two
      distinct contexts (formal vs. informal) and the written information was
      manipulated under three levels of textspeak: none, low, and high. Participants
      judged the author as less conscientious and less open but more emotionally stable
      when textspeak was used. However, context had no impact. Personality perceptions
      of textspeak users differ to those who write in Standard English, and this is
      likely to extend to informal impression management contexts (e.g., online
      dating). These findings also have a number of implications, for example in terms
      of screening applicants via social media. 

PMID- 25751046
TI  - The use of social networking sites for relationship maintenance in long-distance
      and geographically close romantic relationships.
AB  - Social networking sites (SNS) play an increasingly important role in maintaining
      geographically close romantic relationships (GCRR). However, knowledge about SNS
      use in long-distance romantic relationships (LDRR) is still lacking. The present
      study examined the relative importance of SNS in maintaining LDRR compared to
      GCRR, particularly with regard to the use of SNS to express involvement (via
      relational maintenance behaviors) and to gauge a partner's involvement (via
      partner surveillance and jealousy) in the relationship. An online survey was
      conducted among predominantly young adult Facebook users who were in a romantic
      relationship (N=272). Results showed that participants who were in a LDRR
      reported higher levels of relational maintenance behaviors through SNS than
      participants who were in a GCRR. Also, as compared to participants who were in a
      GCRR, participants who were in a LDRR used SNS more for partner surveillance and
      experienced higher levels of SNS jealousy. 

PMID- 25751047
TI  - An exploration of motivations for two screen viewing, social interaction
      behaviors, and factors that influence viewing intentions.
AB  - This study explores whether, and how, motivations for two screen viewing
      predicted social interaction behaviors and subsequent viewing intention of TV
      programs. A total of 453 respondents who responded that they use social
      networking sites (SNSs) via smartphones and actively watch entertainment programs
      completed an online survey questionnaire. In agreement with uses and
      gratifications assumptions, motivations for TSV predicted distinctive sets of
      social interaction behaviors, which mediated the influence of motivations on
      viewing intentions. Respondents' two screen viewing was meaningfully related with
      social interaction, engagement with programs, information seeking, and passing
      time. Results suggest that two screen viewing could provide shared experiences
      nourishing social capital and reintegrate TV audiences by social adhesive
      resulting from TV with SNSs. 

PMID- 25751048
TI  - Influence of a multidimensional measure of attitudes on motives to use social
      networking sites.
AB  - Positive attitudes toward a new communication technology tend to be a significant
      motivator in subsequent adoption and use. The recent spurt in the adoption of
      social media tools such as social networking sites (SNSs) demands the examination
      of attitudinal variables on motives to use these Web sites. This study explicated
      a multidimensional measure of attitudes toward SNSs and tested a theoretical
      model to examine the effect of attitudes on motives to use SNSs and SNS activity.
      Participants (N=674) completed a cross-sectional survey consisting of measures of
      attitudes toward SNSs, motives of SNS use, and level of activity. Results showed
      support for a revised model in which attitudinal variables-ease of use, self
      disclosure, and social connection-strongly predicted motives of SNS use such as
      passing time, information/entertainment, social conformity, and, most
      importantly, socialization. The motive of using SNSs as a social tool superseded
      the direct effect of other motives on SNS activity, suggesting that users'
      primary activity on SNSs was for socialization and for relational development and
      maintenance. 

PMID- 25751049
TI  - The role of attachment style in Facebook use and social capital: evidence from
      university students and a national sample.
AB  - Social networking sites (SNSs) can be beneficial tools for users to gain social
      capital. Although social capital consists of emotional and informational
      resources accumulated through interactions with strong or weak social network
      ties, the existing literature largely ignores attachment style in this context.
      This study employed attachment theory to explore individuals' attachment
      orientations toward Facebook usage and toward online and offline social capital.
      A university student sample (study 1) and a representative national sample (study
      2) showed consistent results. Secure attachment was positively associated with
      online bonding and bridging capital and offline bridging capital. Additionally,
      secure attachment had an indirect effect on all capital through Facebook time.
      Avoidant attachment was negatively associated with online bonding capital.
      Anxious-ambivalent attachment had a direct association with online bonding
      capital and an indirect effect on all capital through Facebook. Interaction
      frequency with good friends on Facebook positively predicted all online and
      offline capital, whereas interaction frequency with average friends on Facebook
      positively predicted online bridging capital. Interaction frequency with
      acquaintances on Facebook was negatively associated with offline bonding capital.
      The study concludes that attachment style is a significant factor in guiding
      social orientation toward Facebook connections with different ties and influences
      online social capital. The study extends attachment theory among university
      students to a national sample to provide more generalizable evidence for the
      current literature. Additionally, this study extends attachment theory to the SNS
      setting with a nuanced examination of types of Facebook friends after controlling
      extraversion. Implications for future research are discussed. 

PMID- 25751050
TI  - An analysis of more than 1,400 articles, 900 scales, and 17 years of research:
      the state of scales in cyberpsychology, behavior, and social networking.
AB  - Cyberpsychology is a recently emergent field that examines the impact of
      technology upon human cognition and behavior. Given its infancy, authors have
      rapidly created new measures to gauge their constructs of interest.
      Unfortunately, few of these authors have had the opportunity to test their
      scales' psychometric properties and validity. This is concerning, as many
      theoretical assumptions may be founded upon scales with inadequate attributes. If
      this were found to be true, then previous findings in cyberpsychology studies
      would need to be retested, and future research would need to shift its focus to
      creating psychometrically sound and valid measures. To provide inferences on this
      concern, the current study examines the article reporting, scale creation, and
      scale reliabilities of every article published in Cyberpsychology, Behavior, and
      Social Networking from its inception to July 2014. The final data set encompassed
      the coding of 1,478 individual articles, including 921 scales, and spanning 17
      years. The results demonstrate that the simple survey methodology has become more
      popular over time. Authors are gradually applying empirically tested scales.
      However, self-created measures are still the most popular, leading to concerns
      about the measures' validity. Also, the use of multi-item measures has increased
      over time, but many articles still fail to report adequate information to assess
      the reliability of the applied scales. Lastly, the average scale reliability is
      0.81, which barely meets standard cutoffs. Overall, these results are not overly
      concerning, but suggestions are given on methods to improve the reporting of
      measures, the creation of scales, and the state of cyberpsychology. 

PMID- 25751051
TI  - Weight concerns scale applied to college students: comparison between pencil-and
      paper and online formats.
AB  - Online data collection is becoming increasingly common and has some advantages
      compared to traditional paper-and-pencil formats, such as reducing loss of data,
      increasing participants' privacy, and decreasing the effect of social
      desirability. However, the validity and reliability of this administration format
      must be established before results can be considered acceptable. The aim of this
      study was to evaluate the validity, reliability, and equivalence of paper-and
      pencil and online versions of the Weight Concerns Scale (WCS) when applied to
      Brazilian university students. A crossover design was used, and the Portuguese
      version of the WCS (in both paper-and-pencil and online formats) was completed by
      100 college students. The results indicated adequate fit in both formats. The
      simultaneous fit of data for both groups was excellent, with strong invariance
      between models. Adequate convergent validity, internal consistency, and mean
      score equivalence of the WCS in both formats were observed. Thus, the WCS
      presented adequate reliability and validity in both administration formats, with
      equivalence/stability between answers. 

PMID- 25751054
TI  - Correction.
AB  - In the January 2015 issue of Cyberpsychology, Behavior, and Social Networking
      (vol. 18, no. 1, pp. 3-7), the article "Individual Differences in Cyber Security
      Behaviors: An Examination of Who Is Sharing Passwords." by Prof. Monica Whitty et
      al., has an error in wording in the abstract. The sentence in question was
      originally printed as: Contrary to our hypotheses, we found older people and
      individuals who score high on self-monitoring were more likely to share
      passwords. It should read: Contrary to our hypotheses, we found younger people
      and individuals who score high on self-monitoring were more likely to share
      passwords. The authors wish to apologize for the error.

PMID- 25751055
TI  - Metallic MoO2 cocatalyst significantly enhances visible-light photocatalytic
      hydrogen production over Mo2/Zn0.5Cd0.5S heterojunction.
AB  - As semiconductor-based nanoheterostructures play a decisive role in current
      electronics and optoelectronics, the introduction of active heterojunctions can
      afford new and improved capabilities that will enhance the conversion of solar
      energy into chemical energy. In this work, a novel metal/semiconductor
      MoO2/Zn0.5Cd0.5S heterojunction has been designed and prepared to significantly
      enhance photocatalytic H2 production efficiency. The photocatalytic activity of
      the as-prepared MoO2/Zn0.5Cd0.5S for H2 generation from water under visible-light
      irradiation (lambda >= 420 nm) is measured. MoO2/Zn0.5Cd0.5S hybrid nanoparticles
      have a higher photocatalytic activity than Zn0.5Cd0.5S even without the noble
      metal cocatalyst. The results show that the rate of H2 evolution over annealed
      MoO2/Zn0.5Cd0.5S is about 13 times higher than that of Zn0.5Cd0.5S alone, and 10
      times higher than that of simply mixed MoO2/Zn0.5Cd0.5S. Implying that the strong
      coupling at the interface of MoO2 and Zn0.5Cd0.5S facilitates electron transfer
      from the conduction band of Zn0.5Cd0.5S to metallic MoO2, thus promoting the
      separation of photogenerated electrons and holes. MoO2 (2 wt%)/Zn0.5Cd0.5S
      heterostructured photocatalyst calcined at 673 K achieves the optimal overall
      activity for H2 evolution. The introduction of metallic MoO2 cocatalyst leads to
      a remarkable improvement in the photo current and photocatalytic H2 production
      activity of Zn0.5Cd0.5S, and the content of MoO2 in this catalyst has an
      important influence on the photocatalytic activity. It is shown that 2 wt%
      metallic MoO2 loaded on Zn0.5Cd0.5S sample produces a maximum photocatalytic H2
      production rate of 252.4 MUmol h(-1). The junctions formed between metallic MoO2
      and semiconductor Zn0.5Cd0.5S by calcination play a key role in high
      photocatalytic water splitting to produce H2. Our study demonstrates that
      metallic MoO2 is an excellent H2 evolution cocatalyst, and could be used as a
      cocatalyst for other semiconductors to improve performances.

PMID- 25751056
TI  - Uptake and distribution of soil applied zinc by citrus trees-addressing
      fertilizer use efficiency with 68Zn labeling.
AB  - The zinc (Zn) supply increases the fruit yield of Citrus trees that are grown,
      especially in the highly weathered soils of the tropics due to the inherently low
      nutrient availability in the soil solution. Leaf sprays containing micronutrients
      are commonly applied to orchards, even though the nutrient supply via soil could
      be of practical value. This study aimed to evaluate the effect of Zn fertilizers
      that are applied to the soil surface on absorption and partitioning of the
      nutrient by citrus trees. A greenhouse experiment was conducted with one-year-old
      sweet orange trees. The plants were grown in soils with different textures (18.1
      or 64.4% clay) that received 1.8 g Zn per plant, in the form of either ZnO or
      ZnSO4 enriched with the stable isotope 68Zn. Zinc fertilization increased the
      availability of the nutrient in the soil and the content in the orange trees.
      Greater responses were obtained when ZnSO4 was applied to the sandy loam soil due
      to its lower specific metal adsorption compared to that of the clay soil. The
      trunk and branches accumulated the most fertilizer-derived Zn (Zndff) and thus
      represent the major reserve organ for this nutrient in the plant. The trees
      recovered up to 4% of the applied Zndff. Despite this relative low recovery, the
      Zn requirement of the trees was met with the selected treatment based on the
      total leaf nutrient content and increased Cu/Zn-SOD activity in the leaves. We
      conclude that the efficiency of Zn fertilizers depends on the fertilizer source
      and the soil texture, which must be taken into account by guidelines for fruit
      crop fertilization via soil, in substitution or complementation of traditional
      foliar sprays. 

PMID- 25751057
TI  - ChIP-nexus enables improved detection of in vivo transcription factor binding
      footprints.
AB  - Understanding how eukaryotic enhancers are bound and regulated by specific
      combinations of transcription factors is still a major challenge. To better map
      transcription factor binding genome-wide at nucleotide resolution in vivo, we
      have developed a robust ChIP-exo protocol called ChIP-nexus (chromatin
      immunoprecipitation experiments with nucleotide resolution through exonuclease,
      unique barcode and single ligation), which utilizes an efficient DNA self
      circularization step during library preparation. Application of ChIP-nexus to
      four proteins--human TBP and Drosophila NFkB, Twist and Max--shows that it
      outperforms existing ChIP protocols in resolution and specificity, pinpoints
      relevant binding sites within enhancers containing multiple binding motifs, and
      allows for the analysis of in vivo binding specificities. Notably, we show that
      Max frequently interacts with DNA sequences next to its motif, and that this
      binding pattern correlates with local DNA-sequence features such as DNA shape.
      ChIP-nexus will be broadly applicable to the study of in vivo transcription
      factor binding specificity and its relationship to cis-regulatory changes in
      humans and model organisms.

PMID- 25751058
TI  - Acetylation site specificities of lysine deacetylase inhibitors in human cells.
AB  - Lysine deacetylases inhibitors (KDACIs) are used in basic research, and many are
      being investigated in clinical trials for treatment of cancer and other diseases.
      However, their specificities in cells are incompletely characterized. Here we
      used quantitative mass spectrometry (MS) to obtain acetylation signatures for 19
      different KDACIs, covering all 18 human lysine deacetylases. Most KDACIs
      increased acetylation of a small, specific subset of the acetylome, including
      sites on histones and other chromatin-associated proteins. Inhibitor treatment
      combined with genetic deletion showed that the effects of the pan-sirtuin
      inhibitor nicotinamide are primarily mediated by SIRT1 inhibition. Furthermore,
      we confirmed that the effects of tubacin and bufexamac on cytoplasmic proteins
      result from inhibition of HDAC6. Bufexamac also triggered an HDAC6-independent,
      hypoxia-like response by stabilizing HIF1-alpha, providing a possible mechanistic
      explanation of its adverse, pro-inflammatory effects. Our results offer a systems
      view of KDACI specificities, providing a framework for studying function of
      acetylation and deacetylases. 

PMID- 25751059
TI  - BAI1 regulates spatial learning and synaptic plasticity in the hippocampus.
AB  - Synaptic plasticity is the ability of synapses to modulate the strength of
      neuronal connections; however, the molecular factors that regulate this feature
      are incompletely understood. Here, we demonstrated that mice lacking brain
      specific angiogenesis inhibitor 1 (BAI1) have severe deficits in hippocampus
      dependent spatial learning and memory that are accompanied by enhanced long-term
      potentiation (LTP), impaired long-term depression (LTD), and a thinning of the
      postsynaptic density (PSD) at hippocampal synapses. We showed that compared with
      WT animals, mice lacking Bai1 exhibit reduced protein levels of the canonical PSD
      component PSD-95 in the brain, which stems from protein destabilization. We
      determined that BAI1 prevents PSD-95 polyubiquitination and degradation through
      an interaction with murine double minute 2 (MDM2), the E3 ubiquitin ligase that
      regulates PSD-95 stability. Restoration of PSD-95 expression in hippocampal
      neurons in BAI1-deficient mice by viral gene therapy was sufficient to compensate
      for Bai1 loss and rescued deficits in synaptic plasticity. Together, our results
      reveal that interaction of BAI1 with MDM2 in the brain modulates PSD-95 levels
      and thereby regulates synaptic plasticity. Moreover, these results suggest that
      targeting this pathway has therapeutic potential for a variety of neurological
      disorders. 

PMID- 25751060
TI  - MicroRNA-188 regulates age-related switch between osteoblast and adipocyte
      differentiation.
AB  - Bone marrow mesenchymal stem cells (BMSCs) exhibit an age-dependent reduction in
      osteogenesis that is accompanied by an increased propensity toward adipocyte
      differentiation. This switch increases adipocyte numbers and decreases the number
      of osteoblasts, contributing to age-related bone loss. Here, we found that the
      level of microRNA-188 (miR-188) is markedly higher in BMSCs from aged compared
      with young mice and humans. Compared with control mice, animals lacking miR-188
      showed a substantial reduction of age-associated bone loss and fat accumulation
      in bone marrow. Conversely, mice with transgenic overexpression of miR-188 in
      osterix+ osteoprogenitors had greater age-associated bone loss and fat
      accumulation in bone marrow relative to WT mice. Moreover, using an aptamer
      delivery system, we found that BMSC-specific overexpression of miR-188 in mice
      reduced bone formation and increased bone marrow fat accumulation. We identified
      histone deacetylase 9 (HDAC9) and RPTOR-independent companion of MTOR complex 2
      (RICTOR) as the direct targets of miR-188. Notably, BMSC-specific inhibition of
      miR-188 by intra-bone marrow injection of aptamer-antagomiR-188 increased bone
      formation and decreased bone marrow fat accumulation in aged mice. Together, our
      results indicate that miR-188 is a key regulator of the age-related switch
      between osteogenesis and adipogenesis of BMSCs and may represent a potential
      therapeutic target for age-related bone loss. 

PMID- 25751062
TI  - RNF4-mediated polyubiquitination regulates the Fanconi anemia/BRCA pathway.
AB  - The Fanconi anemia/BRCA (FA/BRCA) pathway is a DNA repair pathway that is
      required for excision of DNA interstrand cross-links. The 17 known FA proteins,
      along with several FA-associated proteins (FAAPs), cooperate in this pathway to
      detect, unhook, and excise DNA cross-links and to subsequently repair the double
      strand breaks generated in the process. In the current study, we identified a
      patient with FA with a point mutation in FANCA, which encodes a mutant FANCA
      protein (FANCAI939S). FANCAI939S failed to bind to the FAAP20 subunit of the FA
      core complex, leading to decreased stability. Loss of FAAP20 binding exposed a
      SUMOylation site on FANCA at amino acid residue K921, resulting in E2 SUMO
      conjugating enzyme UBC9-mediated SUMOylation, RING finger protein 4-mediated
      (RNF4-mediated) polyubiquitination, and proteasome-mediated degradation of FANCA.
      Mutation of the SUMOylation site of FANCA rescued the expression of the mutant
      protein. Wild-type FANCA was also subject to SUMOylation, RNF4-mediated
      polyubiquitination, and degradation, suggesting that regulated release of FAAP20
      from FANCA is a critical step in the normal FA pathway. Consistent with this
      model, cells lacking RNF4 exhibited interstrand cross-linker hypersensitivity,
      and the gene encoding RNF4 was epistatic with the other genes encoding members of
      the FA/BRCA pathway. Together, the results from our study underscore the
      importance of analyzing unique patient-derived mutations for dissecting complex
      DNA repair processes. 

PMID- 25751063
TI  - A versatile modular vector system for rapid combinatorial mammalian genetics.
AB  - Here, we describe the multiple lentiviral expression (MuLE) system that allows
      multiple genetic alterations to be introduced simultaneously into mammalian
      cells. We created a toolbox of MuLE vectors that constitute a flexible, modular
      system for the rapid engineering of complex polycistronic lentiviruses, allowing
      combinatorial gene overexpression, gene knockdown, Cre-mediated gene deletion, or
      CRISPR/Cas9-mediated (where CRISPR indicates clustered regularly interspaced
      short palindromic repeats) gene mutation, together with expression of fluorescent
      or enzymatic reporters for cellular assays and animal imaging. Examples of tumor
      engineering were used to illustrate the speed and versatility of performing
      combinatorial genetics using the MuLE system. By transducing cultured primary
      mouse cells with single MuLE lentiviruses, we engineered tumors containing up to
      5 different genetic alterations, identified genetic dependencies of molecularly
      defined tumors, conducted genetic interaction screens, and induced the
      simultaneous CRISPR/Cas9-mediated knockout of 3 tumor-suppressor genes.
      Intramuscular injection of MuLE viruses expressing oncogenic H-RasG12V together
      with combinations of knockdowns of the tumor suppressors cyclin-dependent kinase
      inhibitor 2A (Cdkn2a), transformation-related protein 53 (Trp53), and phosphatase
      and tensin homolog (Pten) allowed the generation of 3 murine sarcoma models,
      demonstrating that genetically defined autochthonous tumors can be rapidly
      generated and quantitatively monitored via direct injection of polycistronic MuLE
      lentiviruses into mouse tissues. Together, our results demonstrate that the MuLE
      system provides genetic power for the systematic investigation of the molecular
      mechanisms that underlie human diseases. 

PMID- 25751061
TI  - CXCR3 blockade protects against Listeria monocytogenes infection-induced fetal
      wastage.
AB  - Mammalian pregnancy requires protection against immunological rejection of the
      developing fetus bearing discordant paternal antigens. Immune evasion in this
      developmental context entails silenced expression of chemoattractant proteins
      (chemokines), thereby preventing harmful immune cells from penetrating the
      maternal-fetal interface. Here, we demonstrate that fetal wastage triggered by
      prenatal Listeria monocytogenes infection is driven by placental recruitment of
      CXCL9-producing inflammatory neutrophils and macrophages that promote
      infiltration of fetal-specific T cells into the decidua. Maternal CD8+ T cells
      with fetal specificity upregulated expression of the chemokine receptor CXCR3
      and, together with neutrophils and macrophages, were essential for L.
      monocytogenes-induced fetal resorption. Conversely, decidual accumulation of
      maternal T cells with fetal specificity and fetal wastage were extinguished by
      CXCR3 blockade or in CXCR3-deficient mice. Remarkably, protection against fetal
      wastage and in utero L. monocytogenes invasion was maintained even when CXCR3
      neutralization was initiated after infection, and this protective effect extended
      to fetal resorption triggered by partial ablation of immune-suppressive maternal
      Tregs, which expand during pregnancy to sustain fetal tolerance. Together, our
      results indicate that functionally overriding chemokine silencing at the maternal
      fetal interface promotes the pathogenesis of prenatal infection and suggest that
      therapeutically reinforcing this pathway represents a universal approach for
      mitigating immune-mediated pregnancy complications. 

PMID- 25751066
TI  - Guidelines for the multidisciplinary management of Crohn's perianal fistulas:
      summary statement.

PMID- 25751067
TI  - Guidelines for imaging of Crohn's perianal fistulizing disease.

PMID- 25751065
TI  - Mucosal-associated invariant T cell alterations in obese and type 2 diabetic
      patients.
AB  - Obesity and type 2 diabetes (T2D) are associated with low-grade inflammation,
      activation of immune cells, and alterations of the gut microbiota. Mucosal
      associated invariant T (MAIT) cells, which are innate-like T cells that recognize
      bacterial ligands, are present in blood and enriched in mucosal and inflamed
      tissues. Here, we analyzed MAIT cells in the blood and adipose tissues of
      patients with T2D and/or severe obesity. We determined that circulating MAIT cell
      frequency was dramatically decreased in both patient groups, and this population
      was even undetectable in some obese patients. Moreover, in both patient groups,
      circulating MAIT cells displayed an activated phenotype that was associated with
      elevated Th1 and Th17 cytokine production. In obese patients, MAIT cells were
      more abundant in adipose tissue than in the blood and exhibited a striking IL-17
      profile. Bariatric surgery in obese patients not only improved their metabolic
      parameters but also increased circulating MAIT cell frequency at 3 months after
      surgery. Similarly, cytokine production by blood MAIT cells was strongly
      decreased after surgery. This study reveals profound MAIT cell abnormalities in
      patients harboring metabolic disorders, suggesting their potential role in these
      pathologies. 

PMID- 25751068
TI  - Guidelines for medical treatment of Crohn's perianal fistulas: critical
      evaluation of therapeutic trials.

PMID- 25751064
TI  - KIM-1-mediated phagocytosis reduces acute injury to the kidney.
AB  - Kidney injury molecule 1 (KIM-1, also known as TIM-1) is markedly upregulated in
      the proximal tubule after injury and is maladaptive when chronically expressed.
      Here, we determined that early in the injury process, however, KIM-1 expression
      is antiinflammatory due to its mediation of phagocytic processes in tubule cells.
      Using various models of acute kidney injury (AKI) and mice expressing mutant
      forms of KIM-1, we demonstrated a mucin domain-dependent protective effect of
      epithelial KIM-1 expression that involves downregulation of innate immunity.
      Deletion of the mucin domain markedly impaired KIM-1-mediated phagocytic
      function, resulting in increased proinflammatory cytokine production, decreased
      antiinflammatory growth factor secretion by proximal epithelial cells, and a
      subsequent increase in tissue macrophages. Mice expressing KIM-1Deltamucin had
      greater functional impairment, inflammatory responses, and mortality in response
      to ischemia- and cisplatin-induced AKI. Compared with primary renal proximal
      tubule cells isolated from KIM-1Deltamucin mice, those from WT mice had reduced
      proinflammatory cytokine secretion and impaired macrophage activation. The
      antiinflammatory effect of KIM-1 expression was due to the interaction of KIM-1
      with p85 and subsequent PI3K-dependent downmodulation of NF-kappaB. Hence, KIM-1
      mediated epithelial cell phagocytosis of apoptotic cells protects the kidney
      after acute injury by downregulating innate immunity and inflammation. 

PMID- 25751069
TI  - A comprehensive review of thin-layer drying models used in agricultural products.
AB  - Drying is one of the widely used methods of grain, fruit, and vegetable
      preservation. The important aim of drying is to reduce the moisture content and
      thereby increase the lifetime of products by limiting enzymatic and oxidative
      degradation. In addition, by reducing the amount of water, drying reduces the
      crop losses, improves the quality of dried products, and facilitates its
      transportation, handling, and storage requirements. Drying is a process
      comprising simultaneous heat and mass transfer within the material, and between
      the surface of the material and the surrounding media. Many models have been used
      to describe the drying process for different agricultural products. These models
      are used to estimate drying time of several products under different drying
      conditions, and how to increase the drying process efficiency and also to
      generalize drying curves, for the design and operation of dryers. Several
      investigators have proposed numerous mathematical models for thin-layer drying of
      many agricultural products. This study gives a comprehensive review of more than
      100 different semitheoretical and empirical thin-layer drying models used in
      agricultural products and evaluates the statistical criteria for the
      determination of appropriate model.

PMID- 25751070
TI  - [Position paper of the German Respiratory Society (DGP) on electronic cigarettes
      (E-cigarettes) in cooperation with the following scientific societies and
      organisations: BVKJ, BdP, DGAUM, DGG, DGIM, DGK, DKG, DGSMP, GPP].

PMID- 25751071
TI  - Flat band analogues and flux driven extended electronic states in a class of
      geometrically frustrated fractal networks.
AB  - We demonstrate, by explicit construction, that a single band tight binding
      Hamiltonian defined on a class of deterministic fractals of the b = 3N Sierpinski
      type can give rise to an infinity of dispersionless, flat-band like states which
      can be worked out analytically using the scale invariance of the underlying
      lattice. The states are localized over clusters of increasing sizes, displaying
      the existence of a multitude of localization areas. The onset of localization
      can, in principle, be 'delayed' in space by an appropriate choice of the energy
      of the electron. A uniform magnetic field threading the elementary plaquettes of
      the network is shown to destroy this staggered localization and generate
      absolutely continuous sub-bands in the energy spectrum of these non
      translationally invariant networks. 

PMID- 25751072
TI  - Race, poverty, and medicine in the United States.

PMID- 25751073
TI  - In situ atomic-scale observation of twinning-dominated deformation in nanoscale
      body-centred cubic tungsten.
AB  - Twinning is a fundamental deformation mode that competes against dislocation slip
      in crystalline solids. In metallic nanostructures, plastic deformation requires
      higher stresses than those needed in their bulk counterparts, resulting in the
      'smaller is stronger' phenomenon. Such high stresses are thought to favour
      twinning over dislocation slip. Deformation twinning has been well documented in
      face-centred cubic (FCC) nanoscale crystals. However, it remains unexplored in
      body-centred cubic (BCC) nanoscale crystals. Here, by using in situ high
      resolution transmission electron microscopy and atomistic simulations, we show
      that twinning is the dominant deformation mechanism in nanoscale crystals of BCC
      tungsten. Such deformation twinning is pseudoelastic, manifested through
      reversible detwinning during unloading. We find that the competition between
      twinning and dislocation slip can be mediated by loading orientation, which is
      attributed to the competing nucleation mechanism of defects in nanoscale BCC
      crystals. Our work provides direct observations of deformation twinning as well
      as new insights into the deformation mechanism in BCC nanostructures. 

PMID- 25751074
TI  - Synthesis of ultrathin polymer insulating layers by initiated chemical vapour
      deposition for low-power soft electronics.
AB  - Insulating layers based on oxides and nitrides provide high capacitance, low
      leakage, high breakdown field and resistance to electrical stresses when used in
      electronic devices based on rigid substrates. However, their typically high
      process temperatures and brittleness make it difficult to achieve similar
      performance in flexible or organic electronics. Here, we show that poly(1,3,5
      trimethyl-1,3,5-trivinyl cyclotrisiloxane) (pV3D3) prepared via a one-step,
      solvent-free technique called initiated chemical vapour deposition (iCVD) is a
      versatile polymeric insulating layer that meets a wide range of requirements for
      next-generation electronic devices. Highly uniform and pure ultrathin films of
      pV3D3 with excellent insulating properties, a large energy gap (>8 eV),
      tunnelling-limited leakage characteristics and resistance to a tensile strain of
      up to 4% are demonstrated. The low process temperature, surface-growth character,
      and solvent-free nature of the iCVD process enable pV3D3 to be grown conformally
      on plastic substrates to yield flexible field-effect transistors as well as on a
      variety of channel layers, including organics, oxides, and graphene. 

PMID- 25751075
TI  - Origami structures with a critical transition to bistability arising from hidden
      degrees of freedom.
AB  - Origami is used beyond purely aesthetic pursuits to design responsive and
      customizable mechanical metamaterials. However, a generalized physical
      understanding of origami remains elusive, owing to the challenge of determining
      whether local kinematic constraints are globally compatible and to an incomplete
      understanding of how the folded sheet's material properties contribute to the
      overall mechanical response. Here, we show that the traditional square twist,
      whose crease pattern has zero degrees of freedom (DOF) and therefore should not
      be foldable, can nevertheless be folded by accessing bending deformations that
      are not explicit in the crease pattern. These hidden bending DOF are separated
      from the crease DOF by an energy gap that gives rise to a geometrically driven
      critical bifurcation between mono- and bistability. Noting its potential utility
      for fabricating mechanical switches, we use a temperature-responsive polymer-gel
      version of the square twist to demonstrate hysteretic folding dynamics at the sub
      millimetre scale. 

PMID- 25751076
TI  - A framework for mining actionable navigation patterns from in-store RFID datasets
      via indoor mapping.
AB  - With the quick development of RFID technology and the decreasing prices of RFID
      devices, RFID is becoming widely used in various intelligent services. Especially
      in the retail application domain, RFID is increasingly adopted to capture the
      shopping tracks and behavior of in-store customers. To further enhance the
      potential of this promising application, in this paper, we propose a unified
      framework for RFID-based path analytics, which uses both in-store shopping paths
      and RFID-based purchasing data to mine actionable navigation patterns. Four
      modules of this framework are discussed, which are: (1) mapping from the physical
      space to the cyber space, (2) data preprocessing, (3) pattern mining and (4)
      knowledge understanding and utilization. In the data preprocessing module, the
      critical problem of how to capture the mainstream shopping path sequences while
      wiping out unnecessary redundant and repeated details is addressed in detail. To
      solve this problem, two types of redundant patterns, i.e., loop repeat pattern
      and palindrome-contained pattern are recognized and the corresponding processing
      algorithms are proposed. The experimental results show that the redundant pattern
      filtering functions are effective and scalable. Overall, this work builds a
      bridge between indoor positioning and advanced data mining technologies, and
      provides a feasible way to study customers' shopping behaviors via multi-source
      RFID data. 

PMID- 25751078
TI  - A bio-inspired two-layer sensing structure of polypeptide and multiple-walled
      carbon nanotube to sense small molecular gases.
AB  - In this paper, we propose a bio-inspired, two-layer, multiple-walled carbon
      nanotube (MWCNT)-polypeptide composite sensing device. The MWCNT serves as a
      responsive and conductive layer, and the nonselective polypeptide (40 mer)
      coating the top of the MWCNT acts as a filter into which small molecular gases
      pass. Instead of using selective peptides to sense specific odorants, we propose
      using nonselective, peptide-based sensors to monitor various types of volatile
      organic compounds. In this study, depending on gas interaction and molecular
      sizes, the randomly selected polypeptide enabled the recognition of certain polar
      volatile chemical vapors, such as amines, and the improved discernment of low
      concentration gases. The results of our investigation demonstrated that the
      polypeptide-coated sensors can detect ammonia at a level of several hundred ppm
      and barely responded to triethylamine. 

PMID- 25751077
TI  - A portable automatic endpoint detection system for amplicons of loop mediated
      isothermal amplification on microfluidic compact disk platform.
AB  - In recent years, many improvements have been made in foodborne pathogen detection
      methods to reduce the impact of food contamination. Several rapid methods have
      been developed with biosensor devices to improve the way of performing pathogen
      detection. This paper presents an automated endpoint detection system for
      amplicons generated by loop mediated isothermal amplification (LAMP) on a
      microfluidic compact disk platform. The developed detection system utilizes a
      monochromatic ultraviolet (UV) emitter for excitation of fluorescent labeled LAMP
      amplicons and a color sensor to detect the emitted florescence from target. Then
      it processes the sensor output and displays the detection results on liquid
      crystal display (LCD). The sensitivity test has been performed with detection
      limit up to 2.5 * 10(-3) ng/uL with different DNA concentrations of Salmonella
      bacteria. This system allows a rapid and automatic endpoint detection which could
      lead to the development of a point-of-care diagnosis device for foodborne
      pathogens detection in a resource-limited environment.

PMID- 25751079
TI  - Distributed multi-level supervision to effectively monitor the operations of a
      fleet of autonomous vehicles in agricultural tasks.
AB  - This paper describes a supervisor system for monitoring the operation of
      automated agricultural vehicles. The system analyses all of the information
      provided by the sensors and subsystems on the vehicles in real time and notifies
      the user when a failure or potentially dangerous situation is detected. In some
      situations, it is even able to execute a neutralising protocol to remedy the
      failure. The system is based on a distributed and multi-level architecture that
      divides the supervision into different subsystems, allowing for better management
      of the detection and repair of failures. The proposed supervision system was
      developed to perform well in several scenarios, such as spraying canopy
      treatments against insects and diseases and selective weed treatments, by either
      spraying herbicide or burning pests with a mechanical-thermal actuator. Results
      are presented for selective weed treatment by the spraying of herbicide. The
      system successfully supervised the task; it detected failures such as service
      disruptions, incorrect working speeds, incorrect implement states, and potential
      collisions. Moreover, the system was able to prevent collisions between vehicles
      by taking action to avoid intersecting trajectories. The results show that the
      proposed system is a highly useful tool for managing fleets of autonomous
      vehicles. In particular, it can be used to manage agricultural vehicles during
      treatment operations. 

PMID- 25751080
TI  - Simulations of operation dynamics of different type GaN particle sensors.
AB  - The operation dynamics of the capacitor-type and PIN diode type detectors based
      on GaN have been simulated using the dynamic and drift-diffusion models. The
      drift-diffusion current simulations have been implemented by employing the
      software package Synopsys TCAD Sentaurus. The monopolar and bipolar drift regimes
      have been analyzed by using dynamic models based on the Shockley-Ramo theorem.
      The carrier multiplication processes determined by impact ionization have been
      considered in order to compensate carrier lifetime reduction due to introduction
      of radiation defects into GaN detector material. 

PMID- 25751081
TI  - Distributed efficient similarity search mechanism in wireless sensor networks.
AB  - The Wireless Sensor Network similarity search problem has received considerable
      research attention due to sensor hardware imprecision and environmental parameter
      variations. Most of the state-of-the-art distributed data centric storage (DCS)
      schemes lack optimization for similarity queries of events. In this paper, a DCS
      scheme with metric based similarity searching (DCSMSS) is proposed. DCSMSS takes
      motivation from vector distance index, called iDistance, in order to transform
      the issue of similarity searching into the problem of an interval search in one
      dimension. In addition, a sector based distance routing algorithm is used to
      efficiently route messages. Extensive simulation results reveal that DCSMSS is
      highly efficient and significantly outperforms previous approaches in processing
      similarity search queries. 

PMID- 25751082
TI  - Human sperm aneuploidy after exposure to polycyclic aromatic hydrocarbons.
AB  - The purpose of this cross-sectional study was to investigate whether
      environmental exposure to polycyclic aromatic hydrocarbons (PAHs) was associated
      with sperm aneuploidy. A sample of 181 men who attended an infertility clinic for
      diagnostic purposes and who had a normal semen concentration of 20-300*106
      spermatozoa mL-1 or slight oligozoospermia (semen concentration of 15-20*106
      spermatozoa mL-1; <a href=

PMID- 25751084
TI  - Spectral-domain optical coherence tomography and fundus autofluorescence
      evaluation of torpedo maculopathy.
AB  - The authors describe the spectral-domain optical coherence tomography and fundus
      autofluorescence findings in a case of torpedo maculopathy. Spectral-domain
      optical coherence tomography revealed loss or disruption of the retinal pigment
      epithelium and overlying disruption of the outer neurosensory retina. Fundus
      autofluorescence revealed reduced fundus autofluorescence of the lesion
      surrounded by a rim of increased fundus autofluorescence.

PMID- 25751083
TI  - A Pilot Evaluation of Psychosocial Support for Family Caregivers of Relatives
      with Dementia in Long-Term Care: The Residential Care Transition Module.
AB  - This multiple method pilot evaluation aimed to generate preliminary data on the
      effectiveness of the Residential Care Transition Module (RCTM). The RCTM is a six
      session, 4-month psychosocial intervention designed to help families manage their
      emotional and psychological distress following residential care placement of a
      cognitively impaired relative. Seventeen family caregivers of relatives in a
      nursing home or assisted living memory care unit were randomly assigned to the
      RCTM treatment condition and 19 family caregivers were assigned to a usual care
      control group. Caregivers in the treatment condition reported significantly (p <
      0.05) less emotional distress at 4 and 8 months on self-reported surveys than
      those in the control group. Post-RCTM focus groups emphasized the importance of
      readily available psychosocial support for families following the placement
      transition. The findings suggest that the provision of skilled psychosocial
      support can help families manage emotional distress and crises in the months
      following a cognitively impaired relative's admission to residential long-term
      care.

PMID- 25751085
TI  - Islet Endothelial Cells Derived From Mouse Embryonic Stem Cells.
AB  - The islet endothelium comprises a specialized population of islet endothelial
      cells (IECs) expressing unique markers such as nephrin and alpha-1 antitrypsin
      (AAT) that are not found in endothelial cells in surrounding tissues. However,
      due to difficulties in isolating and maintaining a pure population of these
      cells, the information on these islet-specific cells is currently very limited.
      Interestingly, we have identified a large subpopulation of endothelial cells
      exhibiting IEC phenotype, while deriving insulin-producing cells from mouse
      embryonic stem cells (mESCs). These cells were identified by the uptake of low
      density lipoprotein (LDL) and were successfully isolated and subsequently
      expanded in endothelial cell culture medium. Further analysis demonstrated that
      the mouse embryonic stem cell-derived endothelial cells (mESC-ECs) not only
      express classical endothelial markers, such as platelet endothelial cell adhesion
      molecule (PECAM1), thrombomodulin, intercellular adhesion molecule-1 (ICAM-1),
      and endothelial nitric oxide synthase (eNOS) but also IEC-specific markers such
      as nephrin and AAT. Moreover, mESC-ECs secrete basement membrane proteins such as
      collagen type IV, laminin, and fibronectin in culture and form tubular networks
      on a layer of Matrigel, demonstrating angiogenic activity. Further, mESC-ECs not
      only express eNOS, but also its eNOS expression is glucose dependent, which is
      another characteristic phenotype of IECs. With the ability to obtain highly
      purified IECs derived from pluripotent stem cells, it is possible to closely
      examine the function of these cells and their interaction with pancreatic beta
      cells during development and maturation in vitro. Further characterization of
      tissue-specific endothelial cell properties may enhance our ability to formulate
      new therapeutic angiogenic approaches for diabetes.

PMID- 25751086
TI  - Neurotoxic and neuroactive compounds from Cnidaria: five decades of
      research....and more.
AB  - Cnidarians are numbered among the most venomous organisms. Their venoms are
      contained in intracellular capsules, nematocysts, which inject the content into
      preys/attackers through an eversion system resembling a syringe needle. Several
      cnidarian venoms have activity against the nervous system, being neurotoxic, or
      affect other systems whose functioning is under nerve control. Besides direct
      damage to nerve cells, the activity on ionic conductance, blockade of
      neuromuscular junctions, and influence on action potentials and on voltage-gated
      channels have been described. Therefore, cnidarians can be a useful source of
      nervous system-targeted compounds which could have, in perspective, a role in the
      therapy of some nervous system diseases. Following this idea, this article aims
      to review the existing data about the neuroactive properties of cnidarian venoms
      and their possible usefulness in tackling some neurological diseases as well as
      neurodegenerative age-related diseases whose incidence is expected to raise in
      the next decades owing to the increase of life expectancy. 

PMID- 25751087
TI  - A one-pot O-sulfinative Passerini/oxidation reaction: synthesis of alpha
      (sulfonyloxy)amide derivatives.
AB  - We have developed a one-pot O-sulfinative Passerini/oxidation reaction, in which
      a combination of an aldehyde, an isocyanide, and a sulfinic acid react, followed
      by the addition of mCPBA as an oxidant to give the corresponding alpha
      (sulfonyloxy)amides in high yields. This reaction is the first reported
      demonstration of an isocyanide-based multicomponent reaction using a sulfinic
      acid in place of a carboxylic acid. A wide range of aldehydes and isocyanides are
      applicable to this reaction. 

PMID- 25751088
TI  - High-pressure synthesis, crystal structures, and magnetic properties of 5d double
      perovskite oxides Ca2MgOsO6 and Sr2MgOsO6.
AB  - Double-perovskite oxides Ca2MgOsO6 and Sr2MgOsO6 have been synthesized under high
      pressure and high-temperature conditions (6 GPa and 1500  degrees C). Their
      crystal structures and magnetic properties were studied by a synchrotron X-ray
      diffraction experiment and by magnetic susceptibility, specific heat, isothermal
      magnetization, and electrical resistivity measurements. Ca2MgOsO6 and Sr2MgOsO6
      crystallized in monoclinic (P21/n) and tetragonal (I4/m) double-perovskite
      structures, respectively; the degree of order of the Os and Mg arrangement was
      96% or higher. Although Ca2MgOsO6 and Sr2MgOsO6 are isoelectric, a magnetic-glass
      transition was observed for Ca2MgOsO6 at 19 K, while Sr2MgOsO6 showed an
      antiferromagnetic transition at 110 K. The antiferromagnetic-transition
      temperature is the highest in the family. A first-principles density functional
      approach revealed that Ca2MgOsO6 and Sr2MgOsO6 are likely to be antiferromagnetic
      Mott insulators in which the band gaps open, with Coulomb correlations of ~1.8
      3.0 eV. These compounds offer a better opportunity for the clarification of the
      basis of 5d magnetic sublattices, with regard to the possible use of perovskite
      related oxides in multifunctional devices. The double-perovskite oxides Ca2MgOsO6
      and Sr2MgOsO6 are likely to be Mott insulators with a magnetic-glass (MG)
      transition at ~19 K and an antiferromagnetic (AFM) transition at ~110 K,
      respectively. This AFM transition temperature is the highest among double
      perovskite oxides containing single magnetic sublattices. Thus, these compounds
      offer valuable opportunities for studying the magnetic nature of 5d perovskite
      related oxides, with regard to their possible use in multifunctional devices. 

PMID- 25751089
TI  - Diazirine photocrosslinking recruits activated FTO demethylase complexes for
      specific N(6)-methyladenosine recognition.
AB  - N(6)-methyladenosine (m(6)A) is a prevalent modification of RNAs. m(6)A exists in
      mRNA and plays an important role in RNA biological pathways and in RNA epigenetic
      regulation. We applied diazirine photocrosslinking to the event of m(6)A
      recognition mediated by the fat mass and obesity associated (FTO) demethylase. A
      highly photoreactive diazirine adjacent to m(6)A on the RNA successfully
      recruited activated FTO complexes with an m(6)A preference. The process of
      recognition of m(6)A via FTO using diazirine photocrosslinking was controlled by
      the alpha-ketoglutarate (alpha-KG) cosubstrate and the Fe(II) cofactor, which are
      involved in m(6)A oxidative demethylation. In addition, FTO bound to ssRNAs prior
      to the m(6)A recognition process. Diazirine photocrosslinking contributes to
      increasing the chances of capturing activated FTO complexes with specific m(6)A
      recognition and provides new insights into the dynamic FTO oxidative
      demethylation process. 

PMID- 25751090
TI  - A Mn-54 radiotracer study of Mn isotope solid-liquid exchange during reductive
      transformation of vernadite (delta-MnO2) by aqueous Mn(II).
AB  - We employed Mn-54 radiotracers to characterize the extent and dynamics of Mn atom
      exchange between aqueous Mn(II) and vernadite (delta-Mn(IV)O2) at pH 7.5 under
      anoxic conditions. Exchange of Mn atoms between the solid and liquid phase is
      rapid, reaching dynamic equilibrium in 2-4 days. We propose that during the
      initial stages of reaction, Mn atom exchange occurs through consecutive
      comproportionation-disproportionation reactions where interfacial electron
      transfer from adsorbed Mn(II) to lattice Mn(IV) generates labile Mn(III) cations
      that rapidly disproportionate to reform aqueous Mn(II) and solid-phase Mn(IV).
      Following nucleation of Mn(III)OOH phases, additional exchange likely occurs
      through electron transfer from aqueous Mn(II) to solid-phase Mn(III). Our results
      provide evidence for the fast and extensive production of transient Mn(III)
      species at the vernadite surface upon contact of this substrate with dissolved
      Mn(II). We further show that HEPES buffer is a reductant of lattice Mn(IV) in the
      vernadite structure in our experiments. The methods and results presented here
      introduce application of Mn-54 tracers as a facile tool to further investigate
      the formation kinetics of labile Mn(III) surface species and their impacts on Mn
      oxide structure and reactivity over a range of environmentally relevant
      geochemical conditions. 

PMID- 25751091
TI  - Zn(2+)-selective switch of duplex to hairpin DNA.
AB  - DNA sequences that undergo large changes in secondary structure upon binding of
      small molecules are the basis for molecular switches. Here we report a Zn(2+)
      complex that promotes the conversion of a fully complementary DNA double helix
      into DNA hairpins. The conformational switch is promoted by an isolated Zn(2+)
      complex or by free ZnCl2 and a macrocyclic ligand. The switch is selective for
      Zn(2+) over biologically relevant transition-metal ions including Cu(2+) and
      Fe(2+). The dual ligand/DNA switch is an approach that may improve the
      selectivity for metal-ion-sensing applications. 

PMID- 25751092
TI  - Beta-2 Adrenergic Agonists Are Substrates and Inhibitors of Human Organic Cation
      Transporter 1.
AB  - Beta-2-adrenergic agonists are first line therapeutics in the treatment of asthma
      and chronic obstructive pulmonary disease (COPD). Upon inhalation,
      bronchodilation is achieved after binding to beta2-receptors, which are primarily
      localized on airway smooth muscle cells. Given that beta2-adrenergic agonists
      chemically are bases, they carry net positive charge at physiologic pH value in
      the lungs (i.e., pH 7.4). Here, we studied whether beta2-agonists interact with
      organic cation transporters (OCT) and whether this interaction exerted an
      influence on their passage across the respiratory epithelium to their target
      receptors. [14C]-TEA uptake into proximal (i.e., Calu-3) and distal (i.e., A549
      and NCI-H441) lung epithelial cells was significantly reduced in the presence of
      salbutamol sulfate, formoterol fumarate, and salmeterol xinafoate in vitro.
      Expression of all five members of the OCT/N family has been confirmed in human
      pulmonary epithelial cells in situ and in vitro, which makes the identification
      of the transporter(s) responsible for the beta2-agonist interaction challenging.
      Thus, additional experiments were carried out in HEK-293 cells transfected with
      hOCT1-3. The most pronounced inhibition of organic cation uptake by beta2
      agonists was observed in hOCT1 overexpressing HEK-293 cells. hOCT3 transfected
      HEK-293 cells were affected to a lesser extent, and in hOCT2 transfectants only
      marginal inhibition of organic cation uptake by beta2-agonists was observed.
      Bidirectional transport studies across confluent NCI-H441 cell monolayers
      revealed a net absorptive transport of [3H]-salbutamol, which was sensitive to
      inhibition by the OCT1 modulator, verapamil. Accordingly, salbutamol uptake into
      hOCT1 overexpressing HEK-293 cells was time- and concentration-dependent and
      could be completely blocked by decynium-22. Taken together, our data suggest that
      beta2-agonists are specific substrates and inhibitors of OCT1 in human
      respiratory epithelial cells and that this transporter might play a role in the
      pulmonary disposition of drugs of this class.

PMID- 25751093
TI  - Dynamic tuning of DNA-nanoparticle superlattices by molecular intercalation of
      double helix.
AB  - Nanoparticle (NP) assembly using DNA recognition has emerged as a powerful tool
      for the fabrication of 3D superlattices. In addition to the vast structural
      diversity, this approach provides an avenue for dynamic 3D NP assembly, which is
      promising for the modulation of interparticle distances and, hence, for example,
      for in situ tuning of optical properties. While several approaches have been
      explored for changing NP separations in the lattices using responsiveness of
      single-stranded DNA (ss-DNA), far less work has been done for the manipulation of
      most abundant double-stranded DNA (ds-DNA) motifs. Here, we present a novel
      strategy for modulation of interparticle distances in DNA linked 3D self
      assembled NP lattices by molecular intercalator. We utilize ethidium bromide
      (EtBr) as a model intercalator to demonstrate selective and isotropic lattice
      expansion for three superlattice types (bcc, fcc, and AlB2) due to the
      intercalation of ds-DNA linking NPs. We further show the reversibility of the
      lattice parameter using n-butanol as a retrieving agent as well as an increased
      lattice thermal stability by 12-14  degrees C due to the inclusion of EtBr. The
      proposed intercalator-based strategy permits the creation of reconfigurable and
      thermally stable superlattices, which could lead to tunable and functionally
      responsive materials. 

PMID- 25751094
TI  - Asymmetric biodegradable microdevices for cell-borne drug delivery.
AB  - Use of live cells as carriers for drug-laden particulate structures possesses
      unique advantages for drug delivery. In this work, we report on the development
      of a novel type of particulate structures called microdevices for cell-borne drug
      delivery. The microdevices were fabricated by soft lithography with a disklike
      shape. Each microdevice was composed of a layer of biodegradable thermoplastic
      such as poly(lactic-co-glycolic acid). One face of the thermoplastic layer was
      covalently grafted with a cell-adhesive polyelectrolyte such as poly-l-lysine.
      This asymmetric structure allowed the microdevices to bind to live cells through
      bulk mixing without causing cell aggregation. Moreover, the cell-microdevice
      complexes were largely stable, and the viability and proliferation ability of the
      cells were not affected by the microdevices over a week. In addition, sustained
      release of a mock drug from the microdevices was demonstrated. This type of
      microdevice promises to be clinically useful for sustained intravascular drug
      delivery. 

PMID- 25751095
TI  - Positive teacher and peer relations combine to predict primary school students'
      academic skill development.
AB  - This study examined cross-lagged associations between positive teacher and peer
      relations and academic skill development. Reading and math skills were tested
      among 625 students in kindergarten and Grade 4. Teacher reports of positive
      affect toward each student and classmate reports of peer acceptance were gathered
      in Grades 1-3. The results showed, first, that positive teacher affect toward the
      student and peer acceptance were reciprocally associated: Positive teacher affect
      predicted higher peer acceptance, and higher peer acceptance predicted a higher
      level of positive teacher affect. Second, the effect of positive teacher affect
      on academic skill development was partly mediated via peer acceptance, while the
      effect of early academic skills on peer acceptance was partly mediated via
      positive teacher affect. The results suggest that a warm and supportive teacher
      can increase a student's peer acceptance, which, in turn, is positively
      associated with learning outcomes.

PMID- 25751096
TI  - Time spent in child care: How and why does it affect social development?
AB  - Children who experience early and extensive child care, especially center-based
      care, are rated by teachers as having more externalizing behavior problems than
      are other children. This association is reduced, but not eliminated, when care is
      of high quality, and it varies by socioeconomic disadvantage and the type of
      behavior assessed. We examine the processes that may account for the quantity
      effect, concluding that it occurs primarily among relatively advantaged White non
      Hispanic families. It appears primarily for teacher-rated behavior, especially
      externalizing and low self-control, but is not evident for positive behavior and
      peer interaction skills. Some of the processes accounting for the relation of
      quantity to behavior are most likely to be poor caregiver-child relationships and
      negative peer interactions, not reduced attachment to mothers or lowered maternal
      sensitivity. Many questions remain about duration of effects, developmental and
      individual differences, more nuanced conceptualizations of both care quality and
      social behavior, and variations across cultural and ethnic groups.

PMID- 25751097
TI  - Prompting children to reason proportionally: Processing discrete units as
      continuous amounts.
AB  - Recent studies reveal that children can solve proportional reasoning problems
      presented with continuous amounts that enable intuitive strategies by around 6
      years of age but have difficulties with problems presented with discrete units
      that tend to elicit explicit count-and-match strategies until at least 10 years
      of age. The current study tests whether performance on discrete unit problems
      might be improved by prompting intuitive reasoning with continuous-format
      problems. Participants were kindergarten, second-grade, and fourth-grade students
      (N = 194) assigned to either an experimental condition, where they were given
      continuous amount proportion problems before discrete unit proportion problems,
      or a control condition, where they were given all discrete unit problems. Results
      of a three-way mixed-model analysis of variance examining school grade,
      experimental condition, and block of trials indicated that fourth-grade students
      in the experimental condition outperformed those in the control condition on
      discrete unit problems in the second half of the experiment, but kindergarten and
      second-grade students did not differ by condition. This suggests that older
      children can be prompted to use intuitive strategies to reason proportionally.

PMID- 25751098
TI  - Minority stress and mechanisms of risk for depression and suicidal ideation among
      lesbian, gay, and bisexual youth.
AB  - The experience of minority stress is often named as a cause for mental health
      disparities among lesbian, gay, and bisexual (LGB) youth, including higher levels
      of depression and suicidal ideation. The processes or mechanisms through which
      these disparities occur are understudied. The interpersonal-psychological theory
      of suicide posits 2 key mechanisms for suicidal ideation: perceived
      burdensomeness and thwarted belongingness (Joiner et al., 2009). The aim of the
      current study is to assess the mental health and adjustment among LGB youth
      emphasizing the minority stress model (Meyer, 2003) and the interpersonal
      psychological theory of suicide (Joiner et al., 2009). With a survey of 876 LGB
      self-identified youth, levels of coming-out stress, sexual orientation
      victimization, perceived burdensomeness, thwarted belongingness, depression, and
      suicidal ideation were examined. The results of a multigroup mediation model show
      that for all gender and sexual identity groups, the association of sexual
      orientation victimization with depression and suicidal ideation was mediated by
      perceived burdensomeness. For gay, lesbian, and bisexual girls coming-out stress
      was also found to be related to depression and suicidal ideation, mediated by
      perceived burdensomeness. The results suggest that feeling like a burden to
      "people in their lives" is a critical mechanism in explaining higher levels of
      depression and suicidal ideation among LGB youth. These results have implications
      for community and social support groups, many of which base their interventions
      on decreasing social isolation rather than addressing youths' beliefs of
      burdensomeness. Implications for future research, clinical and community settings
      are discussed.

PMID- 25751099
TI  - Longitudinal relationships among internalization of the media ideal, peer social
      comparison, and body dissatisfaction: implications for the tripartite influence
      model.
AB  - Sociocultural theory of body dissatisfaction posits that internalization of the
      media ideal and appearance comparison are predictors of body dissatisfaction, a
      key risk factor for eating disorders. However, no data exist regarding the
      longitudinal relationships between these variables. The aim of this study was to
      explore longitudinal relationships among internalization of the media-ideal,
      social appearance comparison, and body dissatisfaction. A sample of 277 Grade 7
      school girls (M age = 12.77 years, SD = 0.44) completed measures of
      internalization of the media ideal, social appearance comparison, and body
      dissatisfaction at baseline, 8 months, and 14 months. Path analyses indicated
      that baseline internalization of the media ideal predicted social appearance
      comparison and body dissatisfaction at 8 months, and social appearance comparison
      at 8 months predicted body dissatisfaction at 14 months. A reciprocal effect
      emerged with body dissatisfaction at 8 months predicting internalization of the
      media ideal at 14 months. The findings inform sociocultural theory of body
      dissatisfaction, suggesting that internalization of the media ideal precedes and
      predicts appearance comparison and that body image interventions that target
      internalization of the media ideal, and social appearance comparison as well as
      body dissatisfaction are likely to be effective.

PMID- 25751100
TI  - Longitudinal and integrative tests of family stress model effects on Mexican
      origin adolescents.
AB  - The family stress model represents a common framework through which to examine
      the effects of environmental stressors on adolescent adjustment. The model
      suggests that economic and neighborhood stressors influence youth adjustment via
      disruptions to parenting. Incorporating integrative developmental theory, we
      examined the degree to which parents' cultural value orientations mitigated the
      effects of stressors on parenting disruptions and the degree to which
      environmental adversity qualified the effect of parenting on adolescent
      adjustment. We tested the hypothesized integrative family stress model
      longitudinally in a sample of mother-youth dyads (N = 749) and father-youth dyads
      (N = 467) from Mexican origin families, across 3 times points spanning early to
      middle adolescence. Providing the first longitudinal evidence of family stress
      mediated effects, mothers' perceptions of economic pressure were associated with
      increases in adolescent externalizing symptoms 5 years later via intermediate
      increases in harsh parenting. The remaining findings supported the notion that
      integrative developmental theory can inform family stress model hypothesis
      testing that is culturally and contextually relevant for a wide range of diverse
      families and youth. For example, fathers' perceptions of economic pressure and
      neighborhood danger had important implications for adolescent internalizing, via
      reductions in paternal warmth, but only at certain levels of neighborhood
      adversity. Mothers' familism value orientations mitigated the effects of economic
      pressure on maternal warmth, protecting their adolescents from experiencing
      developmental costs associated with environmental stressors. Results are
      discussed in terms of identifying how integrative developmental theory intersects
      with the family stress model to set diverse youth on different developmental
      pathways.

PMID- 25751101
TI  - Explicit versus implicit solvation effects on the first hyperpolarizability of an
      organic biphotochrome.
AB  - The first hyperpolarizability of the four trans forms of a dithienylethene
      indolinooxazolidine biphotochrome in acetonitrile solution has been evaluated by
      using two solvation models, an explicit and an implicit one. The implicit
      solvation model is the integral equation formalism of the polarizable continuum
      model (IEF-PCM), whereas in the explicit one, the solvent molecules are
      represented by point charges, of which the positions have been generated by Monte
      Carlo simulations whereas the solute is treated quantum mechanically. At optical
      frequencies, first hyperpolarizabilities calculated with the implicit solvation
      model are usually larger than those obtained with the multiscale approach.
      However, both approaches predict similar contrasts, indicating that implicit
      solvation models such as IEF-PCM are well-suited to describe the variations in
      the NLO responses of molecular switches. In addition, the analysis of the
      contrasts of first hyperpolarizabilities shows that the biphotochrome can act as
      a three-state NLO switch. 

PMID- 25751102
TI  - Nutrition of infants and young children (one to three years) and its effect on
      later health: A systematic review of current recommendations (EarlyNutrition
      project).
AB  - BACKGROUND: EarlyNutrition ( www.project-earlynutrition.eu ) is an international
      research project investigating the effects of early nutrition on metabolic
      programming. OBJECTIVE: To summarize, by performing a systematic review, current
      standards, recommendations, guidelines, and regulations (hereafter, referred to
      as documents) on the nutrition of children up to three years of age. Special
      emphasis was placed on long-term effects of early nutrition, such as the risk of
      cardiovascular disease, hypertension, overweight, obesity, metabolic syndrome,
      diabetes, or glucose intolerance. METHODS: MEDLINE, selected databases, and
      websites were searched for documents published between 2008 and January 2013.
      RESULTS: Forty two documents met the inclusion criteria. The strongest and most
      consistent evidence for a protective, long-term effect was documented for
      breastfeeding. Also, limiting the intake of sodium and rapidly absorbed
      carbohydrates, use of a specific meal pattern, reducing the consumption of
      saturated fatty acids by replacing them with polyunsaturated fatty acids, and
      lowering the intake of trans fatty acids, seems beneficial. Many documents did
      not evaluate long-term outcomes of interest to us, or reported insufficient or
      imprecise data. Inconsistency in recommendations for some outcomes and research
      gaps were identified. CONCLUSIONS: Our findings may serve as a helpful tool in
      planning further research, preventive actions against important diet-related
      diseases, and guidelines improvement.

PMID- 25751103
TI  - Effect of short-term hyperglycemia on adipose tissue fluxes of selected cytokines
      in vivo during multiple phases of diet-induced weight loss in obese women.
AB  - CONTEXT: Hyperglycemia is suggested to be one of the drivers of the
      proinflammatory state observed in obese and diabetic patients. OBJECTIVES: The
      objectives of the study was to investigate whether sc abdominal adipose tissue
      (scAT) could be one of the important sources of proinflammatory cytokines
      released in response to short-term hyperglycemia and whether this secretion
      capacity could be influenced by weight loss. DESIGN, PATIENTS, AND INTERVENTIONS:
      Output of cytokines and proteins of acute phase from scAT in response to a 3
      hours hyperglycemic clamp was evaluated in nine obese women in vivo using Fick's
      principle. Moreover, the output of cytokines was analyzed during a multiphase
      dietary intervention consisting of 1 month on a very low-calorie diet and
      subsequent 5-month weight-stabilization phase. MAIN OUTCOME MEASURE(S): The
      levels of cytokines and proteins of acute phase [IL-6, IL-8, IL-1 receptor
      antagonist (IL-1Ra), TNF-alpha, monocyte chemoattractant protein-1 (MCP-1), serum
      amyloid A, and C-reactive protein] in arterial and venous plasma were measured
      during each dietary phase. The insulin sensitivity of scAT in respect to the
      antilipolytic effect of insulin during the clamp was assessed. RESULTS:
      Hyperglycemia increased the output of cytokines IL-6, MCP-1, and IL-1Ra from
      scAT. This effect had a tendency to be reduced after weight loss. The output of
      other proinflammatory substances from scAT into circulation was not detected. The
      diet-induced weight loss was associated with the improvement of antilipolytic
      insulin sensitivity in scAT. CONCLUSIONS: The results suggest that short-term
      hyperglycemia induces an increase of the output of cytokines IL-6, IL-1Ra, and
      MCP-1 from adipose tissue, and this deleterious hyperglycemia effect may be
      attenuated by the diet-induced weight reduction. This lowered responsiveness of
      the inflammation-related system may be an important feature of the weight
      reduction-induced improvement of the metabolic status of obese prediabetic
      individuals.

PMID- 25751104
TI  - Increased hemoglobin A1c threshold for prediabetes remarkably improving the
      agreement between A1c and oral glucose tolerance test criteria in obese
      population.
AB  - CONTEXT: It is unclear why the prevalence of diabetes and prediabetes, especially
      prediabetes, between diagnosed by oral glucose tolerance test (OGTT) and
      hemoglobin A1c (HbA1c) criteria, is substantially discordant. OBJECTIVE: We aimed
      to evaluate the effects of obesity on the agreement between HbA1c and OGTT for
      diagnosing diabetes and prediabetes and identify the optimal HbA1c cutoff values
      in different body mass index (BMI) classifications. DESIGN SETTING AND
      PARTICIPANTS: In a population-based, cross-sectional study in Harbin, China, 4325
      individuals aged 20-74 years without a prior diagnosed diabetes were involved in
      this study. OUTCOME: measure The performance and optimal cutoff points of HbA1c
      were assessed by receiver-operating characteristic curve. The contribution of BMI
      to HbA1c was analyzed by structural equational model. RESULTS: The agreement
      between HbA1c criteria and OGTT decreased with BMI gain (kappa = 0.359, 0.312,
      and 0.275 in a normal weight, overweight, and obese population, respectively).
      The structural equational model results showed that BMI was significantly
      associated with HbA1c in normal glucose tolerance and prediabetes subjects but
      not in diabetes subjects. At a specificity of 80% for prediabetes and 97.5% for
      diabetes, the optimal HbA1c cutoff points for prediabetes and diabetes were 5.6%
      and 6.4% in normal-weight, 5.7% and 6.5% in overweight, and 6.0% and 6.5% in an
      obese population. When the new HbA1c cutoff values were used, the agreement in
      obese subjects increased almost to the level in normal-weight subjects.
      CONCLUSIONS: The poor agreement between HbA1c and OGTT criteria in an obese
      population can be significantly improved through increasing the HbA1c threshold
      for prediabetes.

PMID- 25751105
TI  - Role of Activin A and myostatin in human cancer cachexia.
AB  - CONTEXT: Cachexia is a multifactorial syndrome, characterized by the loss of
      skeletal muscle mass and not fully reversible by nutritional support. Recent
      animal observations suggest that production of Activin A (ActA) and Myostatin
      (Mstn) by some tumors might contribute to cancer cachexia. OBJECTIVE: Our goal
      was to investigate the role of ActA and Mstn in the development of the human
      cancer cachexia. DESIGN/SETTING: The ACTICA study is a cross-sectional study,
      which prospectively enrolled patients from a tertiary-care center between January
      2012 and March 2014. Subjects/Outcome Measures: One hundred fifty two patients
      with colorectal or lung cancer had clinical, nutritional and functional
      assessment. Body composition was measured by CT-scan, anthropometry, and
      bioimpedance. Plasma concentrations of ActA, Mstn, and Follistatin were
      determined. RESULTS: Cachexia was associated with reduced lean and fat mass (p <
      .01 and p < .001), reduced physical function, lower quality of life, and
      increased symptoms (QLQC30; p < .001). Anorexia (SNAQ score < 14) was more common
      in cachectic patients (CC) than in noncachectic patients (CNC) (p < .001). ActA
      concentrations in CC patients were higher than in CNC patients (+40%; p < .001)
      and were correlated positively with weight loss (R = 0.323; p < .001) and
      negatively with the SNAQ score (R = -0.225; p < .01). In contrast, Mstn
      concentrations were decreased in CC patients compared to CNC patients (-35%; p <
      .001). CONCLUSIONS: These results demonstrate an association between circulating
      concentrations of ActA and the presence of the anorexia/cachexia syndrome in
      cancer patients. Given the known muscle atrophic effects of ActA, our study
      suggests that increased circulating concentrations of ActA may contribute to the
      development of cachexia in cancer patients.

PMID- 25751106
TI  - Glycogenin-2 is dispensable for liver glycogen synthesis and glucagon-stimulated
      glucose release.
AB  - CONTEXT: The synthesis of glycogen is initiated by glycogenin. In humans,
      glycogenin-1 is expressed ubiquitously, whereas glycogenin-2 (GN2) is highly
      expressed in liver. It has therefore been suggested that GN2 is a liver isoform
      of glycogenin. In a search for possible copy number variations associated with
      monogenic diabetes, we identified a 102-kb deletion of the X chromosome involving
      the entire GYG2 gene (encoding GN2) in 2 families. OBJECTIVE: The purpose of this
      study was to test whether male GYG2 deletion carriers had abnormal glucose
      metabolism and/or glycogen synthesis. DESIGN, SETTING, AND PATIENTS: Two families
      with diabetes and a GYG2 deletion were investigated with medical history and
      examination, glucagon stimulation tests, and liver biopsies. RESULTS: We
      identified a GYG2 deletion in 3 members of family 1, 8 members of family 2, and 1
      blood donor. The deletion showed no clear cosegregation with diabetes. Deletion
      carriers reported no symptoms related to fasting. Results of cardiac examination
      and abdominal ultrasound imaging were normal. A glucagon stimulation test in 4
      male deletion carriers showed a mean rise in plasma glucose of 3.6 mmol/L (95%
      confidence interval, 2.9-4.2) compared with 2.8 mmol/L (95% confidence interval,
      2.2-3.4) in control subjects. Liver biopsy specimens did not show clear
      morphologic changes by light microscopy and showed the presence of both alpha-
      and beta-glycogen by electron microscopy. We detected GYG1 but not GYG2 mRNA
      expression in the liver biopsy specimens. CONCLUSIONS: This is the first
      evaluation of humans without GN2 expression. Our data indicate that GN2 is not
      required for liver glycogen synthesis and glucagon-stimulated glucose release.

PMID- 25751107
TI  - Brief report: Does PTH increase with age, independent of 25-hydroxyvitamin D,
      phosphate, renal function, and ionized calcium?
AB  - CONTEXT: Circulating PTH concentrations increase with age. It is uncertain
      whether an age-related PTH increase occurs independent of changes in circulating
      25-hydroxyvitamin D, phosphate, renal function, and ionized calcium. OBJECTIVE:
      The purpose of this article was to analyze the relationship between PTH and age,
      controlling for 25-hydroxyvitamin D, phosphate, renal function, and ionized
      calcium. METHODS: This was a retrospective, cross-sectional study analyzing the
      relationship between PTH and age in 2 independent datasets (laboratory 1, n = 17
      275 and laboratory 2, n = 4878). We further analyzed subgroups after excluding
      participants with estimated glomerular filtration rate of <60 mL/min/1.73 m(2) or
      25-hydroxyvitamin D of <50 nmol/L (for subgroups, n = 12 051 for laboratory 1 and
      3473 for laboratory 2). RESULTS: After adjustment for sex, ionized calcium, 25
      hydroxyvitamin D, phosphate, and estimated glomerular filtration rate, each 10
      year increase in age was associated with a 5.0% increase in PTH (95% confidence
      interval [CI], 4.4%-5.6%; P < .001) in laboratory 1 and a 4.2% increase in
      laboratory 2 (95% CI, 3.0%-5.4%; P < .001). In the subgroups, each 10-year
      increase in age was associated with a 6.1% increase in PTH (95% CI, 5.5%-6.8%; P
      < .001) in laboratory 1 and a 4.9% increase (95% CI 3.5%-6.2%; P < .001) in
      laboratory 2. CONCLUSION: PTH concentrations increase with age, independent of 25
      hydroxyvitamin D, ionized calcium, phosphate, and renal function. Further
      research is required to explore the underlying mechanisms and clinical relevance
      and to determine whether the use of age-related PTH reference ranges improves
      diagnostic accuracy, particularly in elderly individuals.

PMID- 25751108
TI  - Hip axis length is a FRAX- and bone density-independent risk factor for hip
      fracture in women.
AB  - CONTEXT: Bone mineral density (BMD) measurement from dual-energy X-ray
      absorptiometry (DXA) is widely used to assess skeletal strength in clinical
      practice, but DXA instruments can also measure biomechanical parameters related
      to skeletal shape. OBJECTIVE: The objective of the study was to determine whether
      DXA-derived hip geometry measures provide information on fracture prediction that
      is independent of hip fracture probability determined from the fracture risk
      assessment tool (FRAX) algorithm. DESIGN AND SETTING: This was a retrospective
      registry study using BMD results for Manitoba, Canada. PATIENTS: Women aged 40
      years and older with baseline hip DXA, derived hip geometry measures, and FRAX
      scores (n = 50 420) participated in the study. MAIN OUTCOME MEASURES:
      Hospitalized hip fracture (n = 1020) diagnosed during 319 137 person-years of
      follow-up (median 6.4 y) was measured. RESULTS: Among the hip geometry measures,
      hip axis length (HAL) showed a consistent association with hip fracture risk when
      adjusted for age [hazard ratio (HR) 1.30 per SD increase, 95% confidence interval
      (CI) 1.22-1.38], and this was unaffected by further adjustment for BMD or FRAX
      score. Adjusted for FRAX score with BMD, there was a significant effect of
      increasing HAL quintile on hip fracture risk (linear trend P < .001); relative to
      quintile 1 (referent), the HR increased from 1.43 (95% CI 1.12-1.82) for quintile
      2, 1.61 (95% CI 1.27-2.04) for quintile 3, 1.85 (95% CI 1.47-2.32) for quintile
      4, and 2.45 (95% CI 1.96-3.05) for quintile 5. There was a modest but significant
      improvement in net reclassification improvement (1.5%) and integrated
      discrimination improvement (0.7%) indices. The effect of HAL was particularly
      strong among younger, nonosteoporotic women (FRAX adjusted HR 1.70 per SD
      increase, 95% CI 1.48-1.94). CONCLUSIONS: DXA-derived hip geometry measurements
      are associated with incident hip fracture risk, but many do not confer
      significant independent predictive information. HAL was found to predict hip
      fractures when adjusted for BMD or FRAX score and may be of clinical value in
      refining hip fracture risk.

PMID- 25751109
TI  - Statins may increase the risk of liver dysfunction in patients treated with
      steroids for active graves' orbitopathy.
AB  - CONTEXT: Intravenous glucocorticoids (IVGC) administered at high doses for the
      treatment of active moderate-severe Graves' orbitopathy (GO) may induce liver
      toxicity. Cumulative doses should not exceed 8 g and strict monitoring of liver
      function is recommended to avoid potentially life-threatening side effects. The 3
      hydroxy-3-methylglutaryl-coenzyme reductase inhibitors, also known as statins,
      are employed to prevent major cardiovascular events. Patients with active GO,
      requiring immunosuppression with IVGC, are often treated with statins also.
      OBJECTIVE: We studied a 64-year-old man and a 58-year-old woman who developed
      significant liver toxicity after moderate doses of IVGC (methylprednisolone 2.3 g
      and 5 g in patients 1 and 2, respectively) and concomitant administration of
      statins. DESIGN AND INTERVENTION: Liver function tests were monitored every two
      weeks. Hepatitis virus markers and serology for autoimmune hepatitis were
      negative. At the occurrence of liver dysfunction (5-fold increase of serum
      aspartate aminotransferase/alanine aminotransferase concentrations), in patient 1
      we stopped simvastatin indefinitely and discontinued IVGC for 2 weeks, whereas in
      patient 2, ongoing treatment with rosuvastatin was discontinued 3 weeks after
      IVGC therapy. RESULTS: In patient 1, off simvastatin, liver function remained
      normal after resuming IVGC. In patient 2, a further increase of the
      aminotransferase values was observed 3 weeks after IVGC discontinuation, with a
      progressive normalization only after statin withdrawal. CONCLUSIONS: Our study
      shows that statins, when concomitantly employed with methylprednisolone, may be a
      cause of liver dysfunction during IVGC in active GO. An accurate pharmacological
      history of all patients who are candidates for IVGC treatment is suggested to
      identify subjects at risk for hepatotoxicity.

PMID- 25751110
TI  - Induction of painless thyroiditis in patients receiving programmed death 1
      receptor immunotherapy for metastatic malignancies.
AB  - CONTEXT: Immunotherapies against immune checkpoints that inhibit T cell
      activation [cytotoxic T lymphocyte antigen 4 (CTLA-4) and programmed cell death 1
      (PD-1)] are emerging and promising treatments for several metastatic
      malignancies. However, the precise adverse effects of these therapies on thyroid
      gland function have not been well described. CASE DESCRIPTION: We report on 10
      cases of painless thyroiditis syndrome (PTS) from a novel etiology, following
      immunotherapy with anti-PD-1 monoclonal antibodies (mAb) during treatment for
      metastatic malignancies. Six patients presented with transient thyrotoxicosis in
      which thyrotropin binding inhibitory immunoglobulins (TBII) were absent for all,
      whereas four patients had evidence of positive antithyroid antibodies. All
      thyrotoxic patients required temporary beta-blocker therapy and had spontaneous
      resolution of thyrotoxicosis with subsequent hypothyroidism. Four patients
      presented with hypothyroidism without a detected preceding thyrotoxic phase,
      occurring 6-8 weeks after initial drug exposure. All of these patients had
      positive antithyroid antibodies and required thyroid hormone replacement therapy
      for a minimum of 6 months. CONCLUSIONS: Patients receiving anti-PD-1 mAb therapy
      should be monitored for signs and symptoms of PTS which may require supportive
      treatment with beta-blockers or thyroid hormone replacement. The anti-PD-1 mAb is
      a novel exogenous cause of PTS and provides new insight into the possible
      perturbations of the immune network that may modulate the development of
      endogenous PTS, including cases of sporadic and postpartum thyroiditis.

PMID- 25751111
TI  - Seven novel deleterious LEPR mutations found in early-onset obesity: a DeltaExon6
      8 shared by subjects from Reunion Island, France, suggests a founder effect.
AB  - CONTEXT: Infrequent mutations have been reported in the leptin receptor (LEPR)
      gene in humans with morbid obesity and endocrine disorders. However LEPR
      mutations are rarely examined in large populations from different ethnicities in
      a given country. OBJECTIVE: We estimated the prevalence of LEPR mutations in
      French patients with severe obesity and evaluated mutated patients' phenotype.
      DESIGN AND PATIENTS: We sequenced the LEPR gene in 535 morbidly obese French
      participants. We conducted clinical investigations to determine whether
      individuals with a novel shared mutation display particular characteristics
      relative to obesity history, body composition, hormonal functions, and the
      outcome of bariatric surgery. RESULTS: We identified 12 patients with a novel
      LEPR mutation (p.C604G, p.L786P, p.H800_N831del, p.Y422H, p.T711NfsX18, p.535
      1G>A, p.P166CfsX7). Six unrelated subjects were carriers of the p.P166CfsX7
      mutation leading to deletion overlapping exons 6 to 8. All subjects originated
      from Reunion Island (France). Their clinical features (severe early-onset
      obesity, food impulsivity, and hypogonadotropic hypogonadism) did not differ from
      other new LEPR mutation carriers. Results concerning weight loss surgery were
      inconsistent in homozygous LEPR mutation carriers. Heterozygous LEPR mutation
      carriers exhibited variable severity of obesity and no endocrine abnormality.
      CONCLUSION: Among seven newly discovered LEPR mutations in this French obese
      population, we identified a LEPR frameshift mutation shared by six subjects from
      Reunion Island. This observation suggests a founder effect in this Indian Ocean
      island with high prevalence of obesity and supports a recommendation for
      systematic screening for this mutation in morbidly obese subjects in this
      population.

PMID- 25751112
TI  - Pregnancy outcomes in women with primary hyperparathyroidism.
AB  - OBJECTIVE: Primary hyperparathyroidism (PHPT) during pregnancy may pose
      considerable risks to mother and fetus. This study examined pregnancy outcomes in
      women with gestational PHPT in relation to clinical and laboratory parameters.
      DESIGN: This study was designed as a retrospective case series. METHODS: The
      study group included 74 women aged 20-40 years who were diagnosed with PHPT after
      a finding of serum calcium >= 10.5 mg/dL on routine screening at a health
      maintenance organization (2005-2013) and who became pregnant during the time of
      hypercalcemia (124 pregnancies). Clinical and laboratory data were collected from
      the files. Pregnancy outcomes were compared with 175 normocalcemic pregnant women
      (431 pregnancies) tested during the same period. RESULTS: The cohort represented
      0.03% of all women of reproductive age tested for serum calcium during the study
      period. Abortion occurred in 12 of 124 pregnancies (9.7%), and other
      complications occurred in 19 (15.3%) with no statistically significant
      differences from controls. Hypercalcemia was first detected during pregnancy in
      14 of 74 women (18.9%) and before pregnancy (mean, 33.4 +/- 29 mo) in 60. Serum
      calcium was measured antenatally in 57 of 124 pregnancies (46%); the mean level
      was 10.7 +/- 0.6 mg/dL (median, 10.6 mg/dL). Measurement of the serum PTH level
      (with consequent diagnosis of PHPT) was performed during the first studied
      pregnancy in 17 of 74 women (23%), before pregnancy (mean, 37.8 +/- 25.5 mo;
      median, 34 mo) in 23 (31.1%), and after delivery (mean, 54.7 +/- 45.7 mo; median,
      35 mo) in 34 (45.9%). Forty-three women (58.1%) underwent parathyroidectomy, six
      during pregnancy, without maternal or fetal complications. No difference was
      found in abortion or any pregnancy-related complication between patients who
      subsequently underwent parathyroidectomy and those who did not. No significant
      correlation was found between calcium level during pregnancy and pregnancy
      outcomes. CONCLUSIONS: Serum calcium levels are usually only mildly elevated
      during pregnancy in women with PHPT. A significant proportion of cases go
      undiagnosed. Mild hypercalcemia in gestational PHPT is generally not associated
      with an increased risk of obstetrical complications.

PMID- 25751113
TI  - Development of a level 1 geriatric outpatient social work screen in a veterans
      primary care clinic.
AB  - Patient Aligned Care Teams (PACT) provide primary care to veterans. We describe
      our experience in a PACT (average age 66, 98% men, 8 medications, 16% yearly
      hospitalization rate) using a nurse-administered screen to identify patients in
      need of intervention by a Masters-level Social Worker. Our screening results--98%
      Positive predictive value (included social work concerns) and 73% negative
      predictive value (excluded social work concerns)--suggest that the nurse
      accurately identified patients. Another 15% of patients were identified by the
      social worker. Similar screens used in interprofessional clinics could help
      target patients in need of further social work care.

PMID- 25751114
TI  - An exploratory path model of the relationships between positive and negative
      adaptation to cancer on quality of life among non-Hodgkin lymphoma survivors.
AB  - Adaptation is an ongoing, cognitive process with continuous appraisal of the
      cancer experience by the survivor. This exploratory study tested a path model
      examining the personal (demographic, disease, and psychosocial) characteristics
      associated with quality of life (QOL) and whether or not adaptation to living
      with cancer may mediate these effects. This study employed path analysis to
      estimate adaptation to cancer. A cross-sectional sample of NHL survivors (N =
      750) was used to test the model. Eligible participants were >= 18 years, at least
      2 years post-diagnosis, and living with or without active disease. Sixty-eight
      percent of the variance was accounted for in QOL. The strongest effect (-0.596)
      was direct by negative adaptation, approximately 3 times that of positive
      adaptation (0.193). The strongest demographic total effects on QOL were age and
      social support; <65 years of age had better QOL and better adaptation compared to
      those >= 65. Of the disease characteristics, comorbidity score had the strongest
      direct effect on QOL; each additional comorbidity was associated with a 0.309
      standard deviation decline on QOL. There were no fully mediated effects through
      positive adaptation alone. Our exploratory findings support the coexistence of
      positive and negative adaptations perception as mediators of personal
      characteristics of the cancer experience. Negative adaptation can affect QOL in a
      positive way. Cancer survivorship is simultaneously shaped by both positive and
      negative adaptation with future research and implications for practice aimed at
      improving QOL.

PMID- 25751115
TI  - Emphasizing the complexity of the relationship: the next decade of attachment
      based psychotherapy research.
AB  - This article focuses on the future of attachment-based psychotherapy research and
      begins with a brief summary of the research that has been done and then explores
      8 predictions for the future. The main emphasis of these predictions is the
      growing complexity in our research needed to capture the mechanisms that
      facilitate or hinder the therapy process for patients with different attachment
      styles. Future researchers will focus more on the interactions between the
      patient and therapist within the sessions, will apply more complex statistical
      analyses to study the dyad, and will integrate different research methods. In
      addition, attachment researchers will focus studies on the changing landscape of
      psychotherapy and explore how attachment can inform Internet-based treatments and
      misperceptions of attachment based on the patients' culture. All in all,
      attachment researchers will start to tackle the more practical issues clinicians
      face, and their work has the potential to significantly improve psychotherapy
      treatment.

PMID- 25751116
TI  - The therapeutic alliance as a predictor of outcome in dialectical behavior
      therapy versus nonbehavioral psychotherapy by experts for borderline personality
      disorder.
AB  - The purpose of the present study was to explore facets of the client- and
      therapist-rated therapeutic alliance as predictors of suicide attempts,
      nonsuicidal self-injury, depression, and introject during the course of 2
      psychosocial treatments for borderline personality disorder. A total of 101 women
      meeting Diagnostic and Statistical Manual of Mental Disorders-IV DSM-IV criteria
      for borderline personality disorder participated in a randomized controlled trial
      of dialectical behavior therapy (DBT) versus community treatment by experts.
      Clients and therapists rated the therapeutic alliance at 4 time points during 1
      year of treatment. Multilevel models showed no significant differences in client
      ratings of the alliance by treatment condition. DBT therapists reported greater
      working strategy consensus early in treatment and an overall greater alliance
      during treatment. Client ratings of commitment and working capacity were
      associated with fewer suicide attempts in DBT. Client ratings of commitment were
      also associated with reduced nonsuicidal self-injury in DBT only. Therapist
      ratings of the alliance were predictive of reduced suicide attempts in both
      treatments. Therapist ratings of the alliance in community treatment by experts
      were predictive of increased nonsuicidal self-injury. Client and therapist
      ratings of the alliance were not significantly associated with changes in
      depression or introject across both treatments. The study supported theoretically
      predicted relationships between facets of the therapeutic alliance in DBT and
      suicidal behavior. Results are discussed in the context of recommendations for
      developing the therapeutic alliance in DBT.

PMID- 25751117
TI  - A festschrift for Charles Gelso.
AB  - Charles Gelso has had a major influence on the field of psychotherapy. This
      article focuses on his contributions to understanding the process and outcome of
      psychotherapy, particularly in relation to the therapeutic relationship, and
      introduces the articles that former students and colleagues wrote for his
      festschrift.

PMID- 25751118
TI  - Countertransference in successful and unsuccessful cases of psychotherapy.
AB  - Countertransference (CT) can provide psychotherapists with important information
      about relationship dynamics with clients, the therapy process, and clinical
      decisions. CT also can lead therapists to view clients and sessions inaccurately,
      feel unduly anxious, and behave in ways that primarily meet their own needs at
      the expense of clients. In summarizing existing scholarship on CT, Fauth (2006)
      noted the need for further research on therapists' subjective experiences of CT
      to enhance current understanding of this pantheoretical construct. To this end,
      we interviewed 18 therapists about their experiences of CT in a recently
      terminated case; half of the therapists described CT in a case they judged to be
      successful, and half described a case they thought was unsuccessful. Interview
      questions were designed to address the 5 components of CT proposed by Hayes
      (1995): origins, triggers, manifestations, effects, and management. A grounded
      theory analysis was conducted and a model describing therapists' experiences of
      CT in successful and unsuccessful therapy was developed. Implications for
      practice, training, and research are discussed.

PMID- 25751119
TI  - "I won't be around forever": Understanding the decision-making experiences of
      adults with severe TBI and their parents.
AB  - There is growing recognition of the right of all individuals, including those
      with cognitive impairment, to make decisions about their own lives. However,
      little is known about how the process of decision making is experienced after
      severe traumatic brain injury (TBI). This study used constructivist grounded
      theory to explore processes used by adults with severe TBI and their parents in
      making decisions about life after injury. Data consisted of 18 individual, in
      depth interviews with four dyads (consisting of an individual with severe TBI and
      his or her parent). The overlying construct emerging from the data was a process
      of reimagining the future, which influenced how participants approached and
      participated in making decisions. In line with this construct, two central themes
      described processes of joint decision making within parent-adult child
      relationships after severe TBI over time: (1) making decisions with parental
      support, and (2) reducing parental involvement. These findings emphasise the
      complexity of supporting decision making after injury, and illustrate that both
      parents and their adult children with TBI use explicit and implicit strategies to
      facilitate increased participation in making decisions. This study also
      underscores the need for brain injury clinicians to consider the needs of parents
      who find themselves in this role. 

PMID- 25751121
TI  - The immortality two-step.

PMID- 25751120
TI  - Post-Acute Care Use and Hospital Readmission after Sepsis.
AB  - RATIONALE: The epidemiology of post-acute care use and hospital readmission after
      sepsis remains largely unknown. OBJECTIVES: To examine the rate of post-acute
      care use and hospital readmission after sepsis and to examine risk factors and
      outcomes for hospital readmissions after sepsis. METHODS: In an observational
      cohort study conducted in an academic health care system (2010-2012), we compared
      post-acute care use at discharge and hospital readmission after 3,620 sepsis
      hospitalizations with 108,958 nonsepsis hospitalizations. We used three
      validated, claims-based approaches to identify sepsis and severe sepsis.
      MEASUREMENTS AND MAIN RESULTS: Post-acute care use at discharge was more likely
      after sepsis, driven by skilled care facility placement (35.4% after sepsis vs.
      15.8%; P < 0.001), with the highest rate observed after severe sepsis.
      Readmission rates at 7, 30, and 90 days were higher postsepsis (P < 0.001).
      Compared with nonsepsis hospitalizations (15.6% readmitted within 30 d), the
      increased readmission risk was present regardless of sepsis severity (27.3% after
      sepsis and 26.0-26.2% after severe sepsis). After controlling for presepsis
      characteristics, the readmission risk was found to be 1.51 times greater (95% CI,
      1.38-1.66) than nonsepsis hospitalizations. Readmissions after sepsis were more
      likely to result in death or transition to hospice care (6.1% vs. 13.3% after
      sepsis; P < 0.001). Independent risk factors associated with 30-day readmissions
      after sepsis hospitalizations included age, malignancy diagnosis,
      hospitalizations in the year prior to the index hospitalization, nonelective
      index admission type, one or more procedures during the index hospitalization,
      and low hemoglobin and high red cell distribution width at discharge.
      CONCLUSIONS: Post-acute care use and hospital readmissions were common after
      sepsis. The increased readmission risk after sepsis was observed regardless of
      sepsis severity and was associated with adverse readmission outcomes.

PMID- 25751122
TI  - Downstream processing and chromatography based analytical methods for production
      of vaccines, gene therapy vectors, and bacteriophages.
AB  - Downstream processing of nanoplexes (viruses, virus-like particles,
      bacteriophages) is characterized by complexity of the starting material, number
      of purification methods to choose from, regulations that are setting the frame
      for the final product and analytical methods for upstream and downstream
      monitoring. This review gives an overview on the nanoplex downstream challenges
      and chromatography based analytical methods for efficient monitoring of the
      nanoplex production. 

PMID- 25751123
TI  - Mediators and Treatment Factors in Intervention for Children Exposed to
      Interparental Violence.
AB  - Changes in children's emotion differentiation, coping skills, parenting stress,
      parental psychopathology, and parent-child interaction were explored as mediators
      of treatment factors in two selective preventive group interventions for children
      exposed to interparental violence (IPV) and their parents. One hundred thirty
      four IPV-exposed children (ages 6-12 years, 52% boys) and their parents were
      randomized to an IPV-focused or common factors community-based group intervention
      and completed baseline, posttest, and follow-up assessments for posttraumatic
      stress (PTS). A multilevel model tested mediators that included children's
      ability to differentiate emotions and coping skills, parenting stress, parental
      psychopathology, and parent-child interactions. In both conditions, exposure to
      nonspecific factors, specific factors unrelated to IPV and trauma-specific
      intervention factors was coded from videotaped child and parent sessions.
      Improved parental mental health mediated the link between greater exposure to
      nonspecific treatment factors and decreases in PTS symptoms. In addition, an
      increase in emotion differentiation and a decrease in parenting stress were
      associated with a decrease in PTS symptoms. Greater exposure to trauma-specific
      factors in child sessions was associated with a small decrease in emotion
      differentiation, an increase in coping skills, and a decrease in PTS symptoms
      over time. Greater exposure to nonspecific treatment factors in child and parent
      sessions was associated with more positive parent-child interaction. Parental
      mental health appears to be an important mechanism of change that can be promoted
      through exposure to nonspecific factors in parent intervention. For children, the
      effect of greater exposure to trauma-specific factors in intervention is less
      clear and may not have clear benefits.

PMID- 25751124
TI  - Cytotoxity of two new coumarin derivatives isolated from Launaea mucronata.
AB  - The chloroform fraction of methanol (MeOH) extract of the aerial parts of Launaea
      mucronata was in vitro investigated for cytotoxicity against HCT116, HepG2 and
      MCF-7 cell lines, and resulted with IC50 = 20.0, 18.6 and 14.30 MUg/mL,
      respectively. The chloroform fraction of the MeOH extract was subjected to
      further fractionation, which led to the isolation of two new coumarin compounds
      (6-isobutyl coumarin and 6-isobutyl-7-methyl- coumarin). The structures of the
      new compounds were elucidated by high field 1D and 2D NMR and ESI-MS
      spectroscopies. Low polar fractions revealed the isolation of other known
      triterpene compounds which were identified according to its spectral data and
      comparison with the literature. New coumarin compounds show high cytotoxicity
      against MCF-7, HCT116 and HepG2 cell lines.

PMID- 25751126
TI  - Magnetic high throughput screening system for the development of nano-sized
      molecularly imprinted polymers for controlled delivery of curcumin.
AB  - Curcumin is a versatile anti-inflammatory and anti-cancer agent known for its low
      bioavailability, which could be improved by developing materials capable of
      binding and releasing drug in a controlled fashion. The present study describes
      the preparation of magnetic nano-sized Molecularly Imprinted Polymers (nanoMIPs)
      for the controlled delivery of curcumin and their high throughput
      characterisation using microtitre plates modified with magnetic inserts. NanoMIPs
      were synthesised using functional monomers chosen with the aid of molecular
      modelling. The rate of release of curcumin from five polymers was studied under
      aqueous conditions and was found to correlate well with the binding energies
      obtained computationally. The presence of specific monomers was shown to be
      significant in ensuring effective binding of curcumin and to the rate of release
      obtained. Characterisation of the polymer particles was carried out using dynamic
      light scattering (DLS) technique and scanning electron microscopy (SEM) in order
      to establish the relationship between irradiation time and particle size. The
      protocols optimised during this study could be used as a blueprint for the
      development of nanoMIPs capable of the controlled release of potentially any
      compound of interest. 

PMID- 25751125
TI  - Potent neutralizing anti-CD1d antibody reduces lung cytokine release in primate
      asthma model.
AB  - CD1d is a receptor on antigen-presenting cells involved in triggering cell
      populations, particularly natural killer T (NKT) cells, to release high levels of
      cytokines. NKT cells are implicated in asthma pathology and blockade of the
      CD1d/NKT cell pathway may have therapeutic potential. We developed a potent anti
      human CD1d antibody (NIB.2) that possesses high affinity for human and cynomolgus
      macaque CD1d (KD ~100 pM) and strong neutralizing activity in human primary cell
      based assays (IC50 typically <100 pM). By epitope mapping experiments, we showed
      that NIB.2 binds to CD1d in close proximity to the interface of CD1d and the Type
      1 NKT cell receptor beta-chain. Together with data showing that NIB.2 inhibited
      stimulation via CD1d loaded with different glycolipids, this supports a mechanism
      whereby NIB.2 inhibits NKT cell activation by inhibiting Type 1 NKT cell receptor
      beta-chain interactions with CD1d, independent of the lipid antigen in the CD1d
      antigen-binding cleft. The strong in vitro potency of NIB.2 was reflected in vivo
      in an Ascaris suum cynomolgus macaque asthma model. Compared with vehicle
      control, NIB.2 treatment significantly reduced bronchoalveolar lavage (BAL)
      levels of Ascaris-induced cytokines IL-5, IL-8 and IL-1 receptor antagonist, and
      significantly reduced baseline levels of GM-CSF, IL-6, IL-15, IL-12/23p40, MIP
      1alpha, MIP-1beta, and VEGF. At a cellular population level NIB.2 also reduced
      numbers of BAL lymphocytes and macrophages, and blood eosinophils and basophils.
      We demonstrate that anti-CD1d antibody blockade of the CD1d/NKT pathway modulates
      inflammatory parameters in vivo in a primate inflammation model, with therapeutic
      potential for diseases where the local cytokine milieu is critical. 

PMID- 25751128
TI  - Energy cost and kinematics of level, uphill and downhill running: fatigue-induced
      changes after a mountain ultramarathon.
AB  - This study aimed to determine whether the fatigue induced by a mountain
      ultramarathon (MUM) led to changes in energy cost and kinematic during level and
      graded running. Pre- and post-race, 14 ultratrail runners ran on a level, uphill
      (5%) and downhill (5%) treadmill at 10 km . h(-1). Kinematic data were acquired
      using a photocell system. Post-race, the downhill energy cost increased by 13.1%
      (P < 0.001). No change was noted in level and uphill running. Duty factor and
      stride frequency were increased, whereas swing time, cycle time and stride length
      were decreased in all conditions (P < 0.05). Contact time was increased and the
      rate of force generation was decreased only in the uphill and downhill conditions
      (P < 0.05). Positive correlations were observed between performance time and the
      pre- to post-changes in the energy cost of level (r = 0.52, P = 0.04) and uphill
      running (r = 0.50, P = 0.04). MUM-induced fatigue resulted in physiological and
      spatiotemporal changes, though the response to fatigue varied considerably
      between running conditions. These changes resulted in a significant increment
      only in the downhill energy cost. Incorporating downhill locomotion in the
      training programmes of ultratrailers may help to improve performance-related
      physiological and biomechanical parameters. 

PMID- 25751129
TI  - Avoiding medical complications during the refeeding of patients with anorexia
      nervosa.
AB  - Nutritional rehabilitation and weight restoration are key underpinnings of the
      treatment protocol for patients with anorexia nervosa. While their inherent state
      of malnutrition and weight loss is certainly not a healthy one, ironically, the
      very essence of the refeeding process, if done injudiciously, can also be unsafe
      for patients with anorexia nervosa. In this article we will provide a review of
      the major complications that may arise during refeeding, how best to avoid them,
      and how to treat them. 

PMID- 25751127
TI  - The development of animal infection models and antifungal efficacy assays against
      clinical isolates of Trichosporon asahii, T. asteroides and T. inkin.
AB  - The present study developed Galleria mellonella and murine infection models for
      the study of Trichosporon infections. The utility of the developed animal models
      was demonstrated through the assessment of virulence and antifungal efficacy for
      7 clinical isolates of Trichosporon asahii, T. asteroides and T. inkin. The
      susceptibility of the Trichosporon isolates to several common antifungal drugs
      was tested in vitro using the broth microdilution and the E-test methods. The E
      test method depicted a lower minimal inhibitory concentration (MIC) for
      amphotericin and a slightly higher MIC for caspofungin, while MICs observed for
      the azoles were different but comparable between both methods. All three
      Trichosporon species established infection in both the G. mellonella and
      immunosuppressed murine models. Species and strain dependent differences were
      observed in both the G. mellonella and murine models. T. asahii was demonstrated
      to be more virulent than the other 2 species in both animal hosts. Significant
      differences in virulence were observed between strains for T. asteroides in the
      murine model. In both animal models, fluconazole and voriconazole were able to
      improve the survival of the animals compared to the untreated control groups
      infected with any of the 3 Trichosporon species. In G. mellonella, amphotericin
      was not able to reduce mortality in any of the 3 species. In contrast,
      amphotericin was able to reduce murine mortality in the T. asahii or T. inkin
      models, respectively. Hence, the developed animal infection models can be
      directly applicable to the future deeper investigation of the molecular
      determinants of Trichosporon virulence and antifungal resistance. 

PMID- 25751130
TI  - Psychological Distress Because of Asking about Suicidal Thoughts: A Randomized
      Controlled Trial among Students.
AB  - The aim of this study was to investigate the effect of the questions from the
      Beck Scale for Suicide Ideation on psychological well-being among healthy
      participants. In a randomized controlled study, 301 participants completed the
      same 4 questionnaires on psychopathology. The experimental group additionally
      answered 21 items of the Beck Scale for Suicide Ideation. The control group
      answered 19 items on Quality of Life. The experimental group showed a
      significantly smaller decrease of negative affect compared to the control
      condition. When analyzing participants with an increase in distress, 80% were
      part of the experimental group. For most participants, answering questions about
      suicide does not affect their mood. A small group of participants did react with
      some distress to the questions about suicide. As the questions about suicide were
      administered immediately before the questions about negative affect, the
      questions about suicide could have worked as a negative mood challenge. Future
      experimental research should further investigate the effect of questions about
      suicide among healthy participants, especially on the long term. 

PMID- 25751131
TI  - Procedural learning during declarative control.
AB  - There is now abundant evidence that human learning and memory are governed by
      multiple systems. As a result, research is now turning to the next question of
      how these putative systems interact. For instance, how is overall control of
      behavior coordinated, and does learning occur independently within systems
      regardless of what system is in control? Behavioral, neuroimaging, and
      neuroscience data are somewhat mixed with respect to these questions. Human
      neuroimaging and animal lesion studies suggest independent learning and are
      mostly agnostic with respect to control. Human behavioral studies suggest active
      inhibition of behavioral output but have little to say regarding learning. The
      results of two perceptual category-learning experiments are described that
      strongly suggest that procedural learning does occur while the explicit system is
      in control of behavior and that this learning might be just as good as if the
      procedural system was controlling the response. These results are consistent with
      the idea that declarative memory systems inhibit the ability of the procedural
      system to access motor output systems but do not prevent procedural learning.

PMID- 25751132
TI  - Impact of cardiovascular treatments and systolic dysfunction on nutritional risk
      in patients with ischemic and valvular heart disease.
AB  - OBJECTIVE: There is a limited knowledge about connections existing between
      impaired systolic function and nutritional risk. The aim of our study was to
      evaluate nutritional risk in patients recently treated for valvular or ischemic
      heart disease, depending on the impairment of left ventricle systolic function
      and chronic cardiovascular therapy. METHODS: Nutritional risk screening was
      applied using a nutritional risk screening (NRS)-2002 [ 1 ] tool in cross
      sectional study settings on patients scheduled for cardiovascular rehabilitation.
      There were 105 patients with impairment of left ventricle systolic function (LVEF
      <= 40) vs 145 consecutive matching peers with preserved LVEF. Percentage weight
      loss history (WLH) from preceding cardiovascular treatments was available for
      more than 85% of studied patients. RESULTS: Mean WLH was 7.7 +/- 4.6%, and NRS
      2002 was 3.6 +/- 1.5. Significant differences in percentage WLH and NRS-2002 were
      found for age groups (p < 0.001, p < 0.001, respectively), cardiovascular
      treatments (p < 0.001, p < 0.001, respectively), and grades of renal function (p
      < 0.001, p < 0.001, respectively), whereas there was no difference on the basis
      of systolic function preservation (both p > 0.05, respectively). Utilization of
      proton pump inhibitors, loop diuretics, and calcium channel antagonists increased
      the odds for pronounced nutritional risk, 2.60 (95% confidence interval [CI],
      1.23-5.47), p = 0.012, vs 2.15 (95% CI, 1.00-4.62), p = 0.049, vs 2.18 (95% CI,
      1.01-4.68), p = 0.046, respectively. Conversely, angiotensin-converting enzyme
      (ACE) inhibitors exhibited protective effects to the nutritional risk, 0.20 (95%
      CI, 0.05-0.89), p = 0.035. CONCLUSION: Clinically, most evocative connections of
      nutritional risk screening and unintentional weight loss were found in relation
      to invasiveness of preceding cardiovascular treatments, rather than preservation
      of systolic function. Protective effects on nutritional risk were found for ACE
      inhibitors, whereas loop diuretics and proton pump inhibitors increased the
      nutritional risk and unintentional loss of weight.

PMID- 25751133
TI  - Data-Driven Personalized Feedback to Patients with Type 1 Diabetes: A Randomized
      Trial.
AB  - BACKGROUND: A mobile phone-based application can be useful for patients with type
      1 diabetes in managing their disease. This results in large datasets accumulated
      on the patient's devices, which can be used for individualized feedback. The
      effect of such feedback is investigated in this article. MATERIALS AND METHODS:
      We developed an application that included a data-driven feedback module known as
      Diastat for patients on self-measured blood glucose regimens. Using a stepped
      wedge design, both groups initially received an application without Diastat.
      Group 1 activated Diastat after 4 weeks, whereas Group 2 activated Diastat 12
      weeks after startup (T1). End points were glycated hemoglobin (HbA1c) level and
      number of out-of-range (OOR) measurements (i.e., outside the range 72-270 mg/dL).
      RESULTS: Thirty patients were recruited to the study, and 15 were assigned to
      each group after the initial meeting. There were no significant differences
      between groups at T1 in HbA1c or OOR events. Overall, all patients had a decrease
      of 0.6 percentage points in mean HbA1c (P < 0.001) and 14.5 in median OOR events
      over 2 weeks (P < 0.001). CONCLUSIONS: The study does not provide evidence that
      data-driven feedback improves glycemic control. The decrease in HbA1c was
      sizeable and significant, even though the study was not powered to detect this.
      The overall improvement in glycemic control suggests that, in general, mobile
      phone-based interventions can be useful in diabetes self-management.

PMID- 25751134
TI  - Revision knee arthroplasty: "art" through science.

PMID- 25751135
TI  - Quantum-size effects and thermal response of anti-Kramer-Pesch vortex core.
AB  - Since the 1960's it has been well known that the basic superconductive quantities
      can exhibit oscillations as functions of the thickness (diameter) in
      superconducting nanofilms (nanowires) due to the size quantization of the
      electronic spectrum. However, very little is known about the effects of quantum
      confinement on the microscopic properties of vortices. Based on a numerical
      solution to the Bogoliubov-de Gennes equations, we study the quantum-size
      oscillations of the vortex core resulting from the sequential interchange of the
      Kramer-Pesch and anti-Kramer-Pesch regimes with changing nanocylinder radius. The
      physics behind the anti-Kramer-Pesch anomaly is displayed by utilizing a semi
      analytical Anderson approximate solution. We also demonstrate that the anti
      Kramer-Pesch vortex core is robust against thermal smearing and results in a
      distinctive two-maxima structure in the local density of states, which can be
      used to identify the existence of the anti-Kramer-Pesch vortex. 

PMID- 25751136
TI  - TLR9 signalling in microglia attenuates seizure-induced aberrant neurogenesis in
      the adult hippocampus.
AB  - Pathological conditions such as epilepsy cause misregulation of adult neural
      stem/progenitor populations in the adult hippocampus in mice, and the resulting
      abnormal neurogenesis leads to impairment in learning and memory. However, how
      animals cope with abnormal neurogenesis remains unknown. Here we show that
      microglia in the mouse hippocampus attenuate convulsive seizure-mediated aberrant
      neurogenesis through the activation of Toll-like receptor 9 (TLR9), an innate
      immune sensor known to recognize microbial DNA and trigger inflammatory
      responses. We found that microglia sense self-DNA from degenerating neurons
      following seizure, and secrete tumour necrosis factor-alpha, resulting in
      attenuation of aberrant neurogenesis. Furthermore, TLR9 deficiency exacerbated
      seizure-induced cognitive decline and recurrent seizure severity. Our findings
      thus suggest the existence of bidirectional communication between the innate
      immune and nervous systems for the maintenance of adult brain integrity. 

PMID- 25751137
TI  - A 150-million-year-old crab larva and its implications for the early rise of
      brachyuran crabs.
AB  - True crabs (Brachyura) are the most successful group of decapod crustaceans. This
      success is most likely coupled to their life history, including two specialised
      larval forms, zoea and megalopa. The group is comparably young, starting to
      diversify only about 100 million years ago (mya), with a dramatic increase in
      species richness beginning approximately 50 mya. Early evolution of crabs is
      still very incompletely known. Here, we report a fossil crab larva, 150 mya,
      documented with up-to-date imaging techniques. It is only the second find of any
      fossil crab larva, but the first complete one, the first megalopa, and the oldest
      one (other fossil ca. 110 mya). Despite its age, the new fossil possesses a very
      modern morphology, being indistinguishable from many extant crab larvae. Hence,
      modern morphologies must have been present significantly earlier than formerly
      anticipated. We briefly discuss the impact of this find on our understanding of
      early crab evolution. 

PMID- 25751138
TI  - Kinetochore-microtubule error correction is driven by differentially regulated
      interaction modes.
AB  - For proper chromosome segregation, sister kinetochores must interact with
      microtubules from opposite spindle poles (bi-orientation). To establish bi
      orientation, aberrant kinetochore-microtubule attachments are disrupted (error
      correction) by aurora B kinase (Ipl1 in budding yeast). Paradoxically, during
      this disruption, new attachments are still formed efficiently to enable fresh
      attempts at bi-orientation. How this is possible remains an enigma. Here we show
      that kinetochore attachment to the microtubule lattice (lateral attachment) is
      impervious to aurora B regulation, but attachment to the microtubule plus end
      (end-on attachment) is disrupted by this kinase. Thus, a new lateral attachment
      is formed without interference, then converted to end-on attachment and released
      if incorrect. This process continues until bi-orientation is established and
      stabilized by tension across sister kinetochores. We reveal how aurora B
      specifically promotes disruption of the end-on attachment through phospho
      regulation of kinetochore components Dam1 and Ndc80. Our results reveal
      fundamental mechanisms for promoting error correction for bi-orientation.

PMID- 25751139
TI  - AMPK modulates Hippo pathway activity to regulate energy homeostasis.
AB  - The Hippo pathway was discovered as a conserved tumour suppressor pathway
      restricting cell proliferation and apoptosis. However, the upstream signals that
      regulate the Hippo pathway in the context of organ size control and cancer
      prevention are largely unknown. Here, we report that glucose, the ubiquitous
      energy source used for ATP generation, regulates the Hippo pathway downstream
      effector YAP. We show that both the Hippo pathway and AMP-activated protein
      kinase (AMPK) were activated during glucose starvation, resulting in
      phosphorylation of YAP and contributing to its inactivation. We also identified
      glucose-transporter 3 (GLUT3) as a YAP-regulated gene involved in glucose
      metabolism. Together, these results demonstrate that glucose-mediated energy
      homeostasis is an upstream event involved in regulation of the Hippo pathway and,
      potentially, an oncogenic function of YAP in promoting glycolysis, thereby
      providing an exciting link between glucose metabolism and the Hippo pathway in
      tissue maintenance and cancer prevention.

PMID- 25751140
TI  - Cellular energy stress induces AMPK-mediated regulation of YAP and the Hippo
      pathway.
AB  - YAP (Yes-associated protein) is a transcription co-activator in the Hippo tumour
      suppressor pathway and controls cell growth, tissue homeostasis and organ size.
      YAP is inhibited by the kinase Lats, which phosphorylates YAP to induce its
      cytoplasmic localization and proteasomal degradation. YAP induces gene expression
      by binding to the TEAD family transcription factors. Dysregulation of the Hippo
      YAP pathway is frequently observed in human cancers. Here we show that cellular
      energy stress induces YAP phosphorylation, in part due to AMPK-dependent Lats
      activation, thereby inhibiting YAP activity. Moreover, AMPK directly
      phosphorylates YAP Ser 94, a residue essential for the interaction with TEAD,
      thus disrupting the YAP-TEAD interaction. AMPK-induced YAP inhibition can
      suppress oncogenic transformation of Lats-null cells with high YAP activity. Our
      study establishes a molecular mechanism and functional significance of AMPK in
      linking cellular energy status to the Hippo-YAP pathway.

PMID- 25751141
TI  - Ppm1b negatively regulates necroptosis through dephosphorylating Rip3.
AB  - The auto-phosphorylation of murine receptor-interacting protein 3 (Rip3) on Thr
      231 and Ser 232 in the necrosome is required to trigger necroptosis. However, how
      Rip3 phosphorylation is regulated is still largely unknown. Here we identified
      protein phosphatase 1B (Ppm1b) as a Rip3 phosphatase and found that Ppm1b
      restricts necroptosis in two settings: spontaneous necroptosis caused by Rip3
      auto-phosphorylation in resting cells, and tumour necrosis factor-alpha (TNF)
      induced necroptosis in cultured cells. We revealed that Ppm1b selectively
      suppresses necroptosis through the dephosphorylation of Rip3, which then prevents
      the recruitment of mixed lineage kinase domain-like protein (Mlkl) to the
      necrosome. We further showed that Ppm1b deficiency (Ppm1b(d/d)) in mice enhanced
      TNF-induced death in a Rip3-dependent manner, and the role of Ppm1b in inhibiting
      necroptosis was evidenced by elevated Rip3 phosphorylation and tissue damage in
      the caecum of TNF-treated Ppm1b(d/d) mice. These data indicate that Ppm1b
      negatively regulates necroptosis through dephosphorylating Rip3 in vitro and in
      vivo.

PMID- 25751142
TI  - HISAT: a fast spliced aligner with low memory requirements.
AB  - HISAT (hierarchical indexing for spliced alignment of transcripts) is a highly
      efficient system for aligning reads from RNA sequencing experiments. HISAT uses
      an indexing scheme based on the Burrows-Wheeler transform and the Ferragina
      Manzini (FM) index, employing two types of indexes for alignment: a whole-genome
      FM index to anchor each alignment and numerous local FM indexes for very rapid
      extensions of these alignments. HISAT's hierarchical index for the human genome
      contains 48,000 local FM indexes, each representing a genomic region of ~64,000
      bp. Tests on real and simulated data sets showed that HISAT is the fastest system
      currently available, with equal or better accuracy than any other method. Despite
      its large number of indexes, HISAT requires only 4.3 gigabytes of memory. HISAT
      supports genomes of any size, including those larger than 4 billion bases.

PMID- 25751143
TI  - Quantitative gene profiling of long noncoding RNAs with targeted RNA sequencing.
AB  - We compared quantitative RT-PCR (qRT-PCR), RNA-seq and capture sequencing
      (CaptureSeq) in terms of their ability to assemble and quantify long noncoding
      RNAs and novel coding exons across 20 human tissues. CaptureSeq was superior for
      the detection and quantification of genes with low expression, showed little
      technical variation and accurately measured differential expression. This
      approach expands and refines previous annotations and simultaneously generates an
      expression atlas. 

PMID- 25751144
TI  - Whole-body immunoPET reveals active SIV dynamics in viremic and antiretroviral
      therapy-treated macaques.
AB  - The detection of viral dynamics and localization in the context of controlled HIV
      infection remains a challenge and is limited to blood and biopsies. We developed
      a method to capture total-body simian immunodeficiency virus (SIV) replication
      using immunoPET (antibody-targeted positron emission tomography). The
      administration of a poly(ethylene glycol)-modified, (64)Cu-labeled SIV Gp120
      specific antibody led to readily detectable signals in the gastrointestinal and
      respiratory tract, lymphoid tissues and reproductive organs of viremic monkeys.
      Viral signals were reduced in aviremic antiretroviral-treated monkeys but
      detectable in colon, select lymph nodes, small bowel, nasal turbinates, the
      genital tract and lung. In elite controllers, virus was detected primarily in
      foci in the small bowel, select lymphoid areas and the male reproductive tract,
      as confirmed by quantitative reverse-transcription PCR (qRT-PCR) and
      immunohistochemistry. This real-time, in vivo viral imaging method has broad
      applications to the study of immunodeficiency virus pathogenesis, drug and
      vaccine development, and the potential for clinical translation. 

PMID- 25751145
TI  - Palivizumab epitope-displaying virus-like particles protect rodents from RSV
      challenge.
AB  - Respiratory syncytial virus (RSV) is the most common cause of serious viral
      bronchiolitis in infants, young children, and the elderly. Currently, there is
      not an FDA-approved vaccine available for RSV, though the mAb palivizumab is
      licensed to reduce the incidence of RSV disease in premature or at-risk infants.
      The palivizumab epitope is a well-characterized, approximately 24-aa helix-loop
      helix structure on the RSV fusion (F) protein (F254-277). Here, we genetically
      inserted this epitope and multiple site variants of this epitope within a
      versatile woodchuck hepadnavirus core-based virus-like particle (WHcAg-VLP) to
      generate hybrid VLPs that each bears 240 copies of the RSV epitope in a highly
      immunogenic arrayed format. A challenge of such an epitope-focused approach is
      that to be effective, the conformational F254-277 epitope must elicit antibodies
      that recognize the intact virus. A number of hybrid VLPs containing RSV F254-277
      were recognized by palivizumab in vitro and elicited high-titer and protective
      neutralizing antibody in rodents. Together, the results from this proof-of
      principle study suggest that the WHcAg-VLP technology may be an applicable
      approach to eliciting a response to other structural epitopes. 

PMID- 25751146
TI  - Relationship of deoxynivalenol content in grain, chaff, and straw with Fusarium
      head blight severity in wheat varieties with various levels of resistance.
AB  - A total of 122 wheat varieties obtained from the Nordic Genetic Resource Center
      were infected artificially with an aggressive Fusariumasiaticum strain in a field
      experiment. We calculated the severity of Fusarium head blight (FHB) and
      determined the deoxynivalenol (DON) content of wheat grain, straw and glumes. We
      found DON contamination levels to be highest in the glumes, intermediate in the
      straw, and lowest in the grain in most samples. The DON contamination levels did
      not increase consistently with increased FHB incidence. The DON levels in the
      wheat varieties with high FHB resistance were not necessarily low, and those in
      the wheat varieties with high FHB sensitivity were not necessarily high. We
      selected 50 wheat genotypes with reduced DON content for future research. This
      study will be helpful in breeding new wheat varieties with low levels of DON
      accumulation. 

PMID- 25751147
TI  - Mycotoxin production in liquid culture and on plants infected with Alternaria
      spp. isolated from rocket and cabbage.
AB  - Fungi belonging to the genus Alternaria are common pathogens of fruit and
      vegetables with some species able to produce secondary metabolites dangerous to
      human health. Twenty-eight Alternaria isolates from rocket and cabbage were
      investigated for their mycotoxin production. Five different Alternaria toxins
      were extracted from synthetic liquid media and from plant material (cabbage,
      cultivated rocket, cauliflower). A modified Czapek-Dox medium was used for the in
      vitro assay. Under these conditions, more than 80% of the isolates showed the
      ability to produce at least one mycotoxin, generally with higher levels for
      tenuazonic acid. However, the same isolates analyzed in vivo seemed to lose their
      ability to produce tenuazonic acid. For the other mycotoxins; alternariol,
      alternariol monomethyl ether, altenuene and tentoxin a good correlation between
      in vitro and in vivo production was observed. In vitro assay is a useful tool to
      predict the possible mycotoxin contamination under field and greenhouse
      conditions. 

PMID- 25751148
TI  - Correction: bioimpedance spectroscopy for assessment of volume status in patients
      before and after general anaesthesia.

PMID- 25751149
TI  - Fluorescently labeled peptide increases identification of degenerated facial
      nerve branches during surgery and improves functional outcome.
AB  - Nerve degeneration after transection injury decreases intraoperative visibility
      under white light (WL), complicating surgical repair. We show here that the use
      of fluorescently labeled nerve binding probe (F-NP41) can improve intraoperative
      visualization of chronically (up to 9 months) denervated nerves. In a mouse model
      for the repair of chronically denervated facial nerves, the intraoperative use of
      fluorescent labeling decreased time to nerve identification by 40% compared to
      surgeries performed under WL alone. Cumulative functional post-operative recovery
      was also significantly improved in the fluorescence guided group as determined by
      quantitatively tracking of the recovery of whisker movement at time intervals for
      6 weeks post-repair. To our knowledge, this is the first description of an
      injectable probe that increases visibility of chronically denervated nerves
      during surgical repair in live animals. Future translation of this probe may
      improve functional outcome for patients with chronic denervation undergoing
      surgical repair. 

PMID- 25751151
TI  - Distinct localisation of lipids in the ovarian follicular environment.
AB  - Obesity is associated with decreased pregnancy rates due, in part, to compromised
      oocyte quality. The aim of the present cross-sectional study of 84 women
      undergoing oocyte aspiration was to: (1) compare insulin, lipids and glucose in
      follicular fluid with serum; (2) determine whether increased body mass index
      (BMI) and waist circumference, hyperinsulinaemia, dyslipidaemia or metabolic
      syndrome altered follicular fluid metabolites; and (3) determine relative lipid
      content in oocytes to reveal any influence of these parameters on oocyte quality
      and IVF outcomes. Insulin, glucose, triglyceride and free fatty acids were lower
      in follicular fluid than blood and not strictly correlated between compartments.
      Insulin, glucose and triglyceride positively correlated with increasing BMI and
      waist circumference in blood and follicular fluid. Insulin increased in
      follicular fluid in association with metabolic syndrome. Free fatty acid
      composition analysis showed saturated fatty acids, particularly palmitic and
      stearic acid, to be more prevalent in follicular fluid than blood. There were no
      associations between follicular fluid metabolites or oocyte lipid content and
      clinical outcomes; however, oocyte immaturity correlated with follicular fluid
      glucose and fatty acid levels, as well as metabolic syndrome. The present study
      confirms that the human ovarian follicular environment surrounding the oocyte
      exhibits a unique metabolite profile compared with blood, with distinct
      localisation of lipids within follicular fluid and oocytes. 

PMID- 25751150
TI  - Alcohol induced alterations to the human fecal VOC metabolome.
AB  - Studies have shown that excessive alcohol consumption impacts the intestinal
      microbiota composition, causing disruption of homeostasis (dysbiosis). However,
      this observed change is not indicative of the dysbiotic intestinal microbiota
      function that could result in the production of injurious and toxic products.
      Thus, knowledge of the effects of alcohol on the intestinal microbiota function
      and their metabolites is warranted, in order to better understand the role of the
      intestinal microbiota in alcohol associated organ failure. Here, we report the
      results of a differential metabolomic analysis comparing volatile organic
      compounds (VOC) detected in the stool of alcoholics and non-alcoholic healthy
      controls. We performed the analysis with fecal samples collected after passage as
      well as with samples collected directly from the sigmoid lumen. Regardless of the
      approach to fecal collection, we found a stool VOC metabolomic signature in
      alcoholics that is different from healthy controls. The most notable metabolite
      alterations in the alcoholic samples include: (1) an elevation in the oxidative
      stress biomarker tetradecane; (2) a decrease in five fatty alcohols with anti
      oxidant property; (3) a decrease in the short chain fatty acids propionate and
      isobutyrate, important in maintaining intestinal epithelial cell health and
      barrier integrity; (4) a decrease in alcohol consumption natural suppressant
      caryophyllene; (5) a decrease in natural product and hepatic steatosis attenuator
      camphene; and (6) decreased dimethyl disulfide and dimethyl trisulfide, microbial
      products of decomposition. Our results showed that intestinal microbiota function
      is altered in alcoholics which might promote alcohol associated pathologies. 

PMID- 25751152
TI  - Investigating different duplication pattern of essential genes in mouse and
      human.
AB  - Gene duplication is one of the major driving forces shaping genome and organism
      evolution and thought to be itself regulated by some intrinsic properties of the
      gene. Comparing the essential genes among mouse and human, we observed that the
      essential genes avoid duplication in mouse while prefer to remain duplicated in
      humans. In this study, we wanted to explore the reasons behind such differences
      in gene essentiality by cross-species comparison of human and mouse. Moreover, we
      examined essential genes that are duplicated in humans are functionally more
      redundant than that in mouse. The proportion of paralog pseudogenization of
      essential genes is higher in mouse than that of humans. These duplicates of
      essential genes are under stringent dosage regulation in human than in mouse. We
      also observed slower evolutionary rate in the paralogs of human essential genes
      than the mouse counterpart. Together, these results clearly indicate that human
      essential genes are retained as duplicates to serve as backed up copies that may
      shield themselves from harmful mutations. 

PMID- 25751154
TI  - Stereoselective synthesis of chiral sulfilimines from N-mesyloxycarbamates: metal
      nitrenes versus metal-nitrenoids species.
AB  - The synthesis of a variety of chiral sulfilimines and sulfoximines is described.
      The amination of thioethers with a chiral N-mesyloxycarbamate was achieved in
      high yields and stereoselectivities using Rh2[(S)-nttl]4 as catalyst in the
      presence of 4-dimethylaminopyridine (DMAP) and a pyridinium salt, such as
      bis(DMAP)CH2Cl2 or a viologen salt. These additives proved instrumental to
      enhance both the yield and the stereochemical discrimination of the reaction.
      Mechanistic studies and control experiments have elucidated the role of these
      additives. DMAP served as an apical ligand for the rhodium catalyst: an X-ray
      crystal structure of the (DMAP)2.[Rh2{(S)-nttl}4] complex was obtained. This
      complex displayed a lower and irreversible redox potential. Control experiments
      with preformed Rh(II)-Rh(III) complex suggested such a catalytically active
      species in the thioether amination process. Diastereoselectivities were
      influenced by the sulfonyloxy leaving group, ruling out the possibility of a
      common metal nitrene species and instead suggesting a rhodium-nitrenoid complex.
      It is believed that the bispyridinium salt played the role of a phase transfer
      catalyst, influencing both the yield and the diastereoselectivity of the
      reaction. 

PMID- 25751153
TI  - MASH1/Ascl1a leads to GAP43 expression and axon regeneration in the adult CNS.
AB  - Unlike CNS neurons in adult mammals, neurons in fish and embryonic mammals can
      regenerate their axons after injury. These divergent regenerative responses are
      in part mediated by the growth-associated expression of select transcription
      factors. The basic helix-loop-helix (bHLH) transcription factor, MASH1/Ascl1a, is
      transiently expressed during the development of many neuronal subtypes and
      regulates the expression of genes that mediate cell fate determination and
      differentiation. In the adult zebrafish (Danio rerio), Ascl1a is also transiently
      expressed in retinal ganglion cells (RGCs) that regenerate axons after optic
      nerve crush. Utilizing transgenic zebrafish with a 3.6 kb GAP43 promoter that
      drives expression of an enhanced green fluorescent protein (EGFP), we observed
      that knock-down of Ascl1a expression reduces both regenerative gap43 gene
      expression and axonal growth after injury compared to controls. In mammals, the
      development of noradrenergic brainstem neurons requires MASH1 expression. In
      contrast to zebrafish RGCs, however, MASH1 is not expressed in the mammalian
      brainstem after spinal cord injury (SCI). Therefore, we utilized adeno-associated
      viral (AAV) vectors to overexpress MASH1 in four month old rat (Rattus
      norvegicus) brainstem neurons in an attempt to promote axon regeneration after
      SCI. We discovered that after complete transection of the thoracic spinal cord
      and implantation of a Schwann cell bridge, animals that express MASH1 exhibit
      increased noradrenergic axon regeneration and improvement in hindlimb joint
      movements compared to controls. Together these data demonstrate that MASH1/Ascl1a
      is a fundamental regulator of axonal growth across vertebrates and can induce
      modifications to the intrinsic state of neurons to promote functional
      regeneration in response to CNS injury. 

PMID- 25751155
TI  - Fast and tunable synthesis of ZrO2 nanocrystals: mechanistic insights into
      precursor dependence.
AB  - In this work, ZrO2 nanocrystals (NCs) are synthesized via a solvothermal
      treatment in benzyl alcohol, which is an established method for the synthesis of
      many metal oxide nanocrystals. We found that the use of microwave heating allows
      for a reduction in reaction time from 2 days in the autoclave to merely 4 h in
      the microwave. Furthermore, we were able to tune the crystallographic phase from
      pure cubic to pure monoclinic zirconia by changing the reaction mechanism through
      the use of a different zirconium precursor. Via GC-MS measurements, we found that
      the release of a strong acid during synthesis controls the key mechanism behind
      the control over crystal phase formation. The as-synthesized ZrO2 NCs (cubic or
      monoclinic) are small in size (3-10 nm), yet aggregated. However, aggregate-free
      NCs are generated through a surface-functionalization with carboxylic acid
      ligands, providing stabilization in apolar solvents via steric hindrance.
      Solution (1)H NMR was used to study the details of this post-modification step
      and the surface chemistry of the resulting aggregate-free NCs. This led to the
      conclusion that not only a different crystal structure but also a different
      surface chemistry is obtained, depending on the precursor composition. 

PMID- 25751156
TI  - BODIPY-derived photoremovable protecting groups unmasked with green light.
AB  - Photoremovable protecting groups derived from meso-substituted BODIPY dyes
      release acetic acid with green wavelengths >500 nm. Photorelease is demonstrated
      in cultured S2 cells. The photocaging structures were identified by our
      previously proposed strategy of computationally searching for carbocations with
      low-energy diradical states as a possible indicator of a nearby productive
      conical intersection. The superior optical properties of these photocages make
      them promising alternatives to the popular o-nitrobenzyl photocage systems. 

PMID- 25751157
TI  - Comprehensive profiling of the rice ubiquitome reveals the significance of lysine
      ubiquitination in young leaves.
AB  - Protein ubiquitination is a major post-translational modification that regulates
      development, apoptosis, responses to environmental cues, and other processes in
      eukaryotes. Although several ubiquitinated proteins have been identified in rice,
      large-scale profiling of the rice ubiquitome has not been reported because of
      limitations in the current analytical methods. Here, we report the first rice
      ubiquitome, determined by combining highly sensitive immune affinity purification
      and high resolution LC-MS/MS. We identified 861 di-Gly-Lys-containing peptides in
      464 proteins in rice leaf cells. Bioinformatic analyses of the ubiquitome
      identified a variety of cellular functions and diverse subcellular localizations
      for the ubiquitinated proteins, and also revealed seven putative ubiquitination
      motifs in rice. Proteins related to binding and catalytic activity were predicted
      to be the preferential targets of lysine ubiquitination. A protein interaction
      network and KEGG analysis indicated that a wide range of signaling and metabolic
      pathways are modulated by protein ubiquitination in rice. Our results demonstrate
      the usefulness of the significantly improved method for assaying proteome-wide
      ubiquitination in plants. The identification of the 464 ubiquitinated proteins in
      rice leaves provides a foundation for the analysis of the physiological roles of
      these ubiquitination-related proteins. 

PMID- 25751159
TI  - Responses of microbial communities to single-walled carbon nanotubes in phenol
      wastewater treatment systems.
AB  - The expanding use of single-walled carbon nanotubes (SWCNTs) raises environmental
      concerns. Wastewater treatment systems are potential recipients of SWCNTs
      containing influent, yet the impacts of SWCNTs on these systems are poorly
      documented. In this study, the microbial responses to SWCNTs in simulated phenol
      wastewater treatment systems were investigated. The phenol removal rates were
      improved in all SWCNTs-treated sequencing batch reactors during the first 20
      days, but when facing higher phenol concentration (1000 mg/L) after 60 days,
      reactors with the highest concentration (3.5 g/L) of SWCNTs exhibited a notably
      decreased phenol removal capacity. Cell viability tests, scanning electron
      microscopy analysis and DNA leakage data suggested that SWCNTs protected microbes
      from inactivation, possibly by producing more bound extracellular polymeric
      substances (EPS), which could create a protective barrier for the microbes.
      Illumina sequencing of 16S rRNA gene amplicons revealed that the bacterial
      diversity did not change significantly except for a minor reduction after the
      immediate addition of SWCNTs. Bacterial community structure significantly shifted
      after SWCNTs addition and did not recover afterward. Zoogloea increased
      significantly upon SWCNTs shocking. At the final stage, Rudaea and Mobilicoccus
      increased, while Burkholderia, Singulisphaera, Labrys and Mucilaginibacter
      decreased notably. The shifts of these dominant genera may be associated with
      altered sludge settling, aromatic degradation and EPS production. This study
      suggested that SWCNTs exerted protective rather than cytotoxic effects on sludge
      microbes of phenol wastewater treatment systems and they affected the bacterial
      community structure and diversity at test concentrations. These findings provide
      new insights into our understanding of the potential effects of SWCNTs on
      wastewater treatment processes. 

PMID- 25751158
TI  - Preconditioning of Cardiosphere-Derived Cells With Hypoxia or Prolyl-4
      Hydroxylase Inhibitors Increases Stemness and Decreases Reliance on Oxidative
      Metabolism.
AB  - Cardiosphere-derived cells (CDCs), which can be isolated from heart explants, are
      a promising candidate cell source for infarcted myocardium regeneration. However,
      current protocols used to expand CDCs require at least 1 month in vitro to obtain
      sufficient cells for transplantation. We report that CDC culture can be optimized
      by preconditioning the cells under hypoxia (2% oxygen), which may reflect the
      physiological oxygen level of the stem cell niche. Under hypoxia, the CDC
      proliferation rate increased by 1.4-fold, generating 6 * 10(6) CDCs with higher
      expression of cardiac stem cell and pluripotency gene markers compared to
      normoxia. Furthermore, telomerase (TERT), cytokines/ligands involved in stem cell
      trafficking (SDF/CXCR-4), erythropoiesis (EPO), and angiogenesis (VEGF) were
      increased under hypoxia. Hypoxic preconditioning was mimicked by treatment with
      two types of hypoxia-inducible factor (HIF) prolyl-4-hydroxylase inhibitors
      (PHDIs): dimethyloxaloylglycine (DMOG) and 2-(1-chloro-4-hydroxyisoquinoline-3
      carboxamido) acetic acid (BIC). Despite the difference in specificity, both PHDIs
      significantly increased c-Kit expression and activated HIF, EPO, and CXCR-4.
      Furthermore, treatment with PHDIs for 24 h increased cell proliferation. Notably,
      all hypoxic and PHDI-preconditioned CDCs had decreased oxygen consumption and
      increased glycolytic metabolism. In conclusion, cells cultured under hypoxia
      could have potentially enhanced therapeutic potential, which can be mimicked, in
      part, by PHDIs.

PMID- 25751161
TI  - Synthesis of the first heteroaryl-substituted boryl complexes: strong stabilizing
      effects of boron-aryl pi-conjugation.
AB  - The first examples of heteroarylboryl complexes were prepared and have been found
      to be unreactive toward a range of strong reductants, strong Lewis bases, and
      halide-abstraction reagents. The inertness of the complexes is attributed to
      strong pi-conjugation between the pi-basic heteroaryl groups and the pi-acidic
      boron atom. This hypothesis is supported by comparison of the structural and
      spectroscopic properties of the heteroarylboryl complexes with analogous
      previously reported homoarylboryl complexes, with the former showing greater
      coplanarity of the aryl ring with the boron atom and much less facile reactivity.

PMID- 25751160
TI  - Nanopore-based DNA-probe sequence-evolution method unveiling characteristics of
      protein-DNA binding phenomena in a nanoscale confined space.
AB  - Almost all of the important functions of DNA are realized by proteins which
      interact with specific DNA, which actually happens in a limited space. However,
      most of the studies about the protein-DNA binding are in an unconfined space.
      Here, we propose a new method, nanopore-based DNA-probe sequence-evolution
      (NDPSE), which includes up to 6 different DNA-probe systems successively designed
      in a nanoscale confined space which unveil the more realistic characteristics of
      protein-DNA binding phenomena. There are several features; for example, first,
      the edge-hindrance and core-hindrance contribute differently for the binding
      events, and second, there is an equilibrium between protein-DNA binding and DNA
      DNA hybridization. 

PMID- 25751162
TI  - Prediction models for the erector spinae muscle cross-sectional area.
AB  - Accurate and reliable "individualized" low back erector spinae muscle (ESM) data
      are of importance to estimate its force producing capacity. Knowing the force
      producing capacity, along with spinal loading, enhances the understanding of low
      back injury mechanisms. The objective of this study was to build regression
      models to estimate the ESM cross-sectional area (CSA). Measurements were taken
      from axial-oblique magnetic resonance imaging (MRI) scans of a large historical
      population [54 females and 53 males at L3/L4, 50 females and 44 males at L4/L5,
      and 41 females and 35 males at L5/S1 levels]. Results suggest that an
      individual's ESM CSA can be accurately estimated based on his/her gender, height,
      and weight. Results further show that there is no significant difference between
      the measured and estimated ESM CSAs, and expected absolute error is less than
      15%. 

PMID- 25751163
TI  - Multiframe denoising of high-speed optical coherence tomography data using
      interframe and intraframe priors.
AB  - Optical coherence tomography (OCT) is an important interferometric diagnostic
      technique, which provides cross-sectional views of biological tissues' subsurface
      microstructures. However, the imaging quality of high-speed OCT is limited by the
      large speckle noise. To address this problem, we propose a multiframe algorithmic
      method to denoise OCT volume. Mathematically, we build an optimization model
      which forces the temporally registered frames to be low-rank and the gradient in
      each frame to be sparse, under the constraints from logarithmic image formation
      and nonuniform noise variance. In addition, a convex optimization algorithm based
      on the augmented Lagrangian method is derived to solve the above model. The
      results reveal that our approach outperforms the other methods in terms of both
      speckle noise suppression and crucial detail preservation.

PMID- 25751164
TI  - The health of young African American men.

PMID- 25751165
TI  - A better pain plan.

PMID- 25751167
TI  - Amplified photoacoustic performance and enhanced photothermal stability of
      reduced graphene oxide coated gold nanorods for sensitive photoacoustic imaging.
AB  - We report a strongly amplified photoacoustic (PA) performance of the new
      functional hybrid material composed of reduced graphene oxide and gold nanorods.
      Due to the excellent NIR light absorption properties of the reduced graphene
      oxide coated gold nanorods (r-GO-AuNRs) and highly efficient heat transfer
      process through the reduced graphene oxide layer, r-GO-AuNRs exhibit excellent
      photothermal stability and significantly higher photoacoustic amplitudes than
      those of bare-AuNRs, nonreduced graphene oxide coated AuNRs (GO-AuNRs), or silica
      coated AuNR, as demonstrated in both in vitro and in vivo systems. The linear
      response of PA amplitude from reduced state controlled GO on AuNR indicates the
      critical role of GO for a strong photothermal effect of r-GO-AuNRs. Theoretical
      studies with finite-element-method lab-based simulation reveal that a 4 times
      higher magnitude of the enhanced electromagnetic field around r-GO-AuNRs can be
      generated compared with bare AuNRs or GO-AuNRs. Furthermore, the r-GO-AuNRs are
      expected to be a promising deep-tissue imaging probe because of extraordinarily
      high PA amplitudes in the 4-11 MHz operating frequency of an ultrasound
      transducer. Therefore, the r-GO-AuNRs can be a useful imaging probe for highly
      sensitive photoacoustic images and NIR sensitive therapeutics based on a strong
      photothermal effect. 

PMID- 25751168
TI  - Redox-responsive polymer-drug conjugates based on doxorubicin and chitosan
      oligosaccharide-g-stearic acid for cancer therapy.
AB  - Here, a biodegradable polymer-drug conjugate of doxorubicin (DOX) conjugated with
      a stearic acid-grafted chitosan oligosaccharide (CSO-SA) was synthesized via
      disulfide linkers. The obtained polymer-drug conjugate DOX-SS-CSO-SA could self
      assemble into nanosized micelles in aqueous medium with a low critical micelle
      concentration. The size of the micelles was 62.8 nm with a narrow size
      distribution. In reducing environments, the DOX-SS-CSO-SA could rapidly
      disassemble result from the cleavage of the disulfide linkers and release the
      DOX. DOX-SS-CSO-SA had high efficiency for cellular uptake and rapidly released
      DOX in reductive intracellular environments. In vitro antitumor activity tests
      showed that the DOX-SS-CSO-SA had higher cytotoxicity against DOX-resistant cells
      than free DOX, with reversal ability up to 34.8-fold. DOX-SS-CSO-SA altered the
      drug distribution in vivo, which showed selectively accumulation in tumor and
      reduced nonspecific accumulation in hearts. In vivo antitumor studies
      demonstrated that DOX-SS-CSO-SA showed efficient suppression on tumor growth and
      relieved the DOX-induced cardiac injury. Therefore, DOX-SS-CSO-SA is a potential
      drug delivery system for safe and effective cancer therapy. 

PMID- 25751169
TI  - N-doped graphitic layer encased cobalt nanoparticles as efficient oxygen
      reduction catalysts in alkaline media.
AB  - Nitrogen doped graphitic layer encased cobalt (N-C@Co) nanoparticles, as novel
      non-precious-metal catalysts for the oxygen reduction reaction (ORR), were
      fabricated by a facile method using cyanamide and cobalt nitrate as precursors.
      The N-C@Co catalysts exhibited comparable catalytic performance, better stability
      and improved methanol tolerance towards the ORR than those of the commercial Pt/C
      catalyst. 

PMID- 25751171
TI  - Generation of transgenic energy cane plants with integration of minimal transgene
      expression cassette.
AB  - Lignocellulosic biomass has the potential to serve as feedstock and direct
      replacement for petrochemicals in the fuel, chemical, pharmaceutical and material
      industries. Energy cane has been identified by the U.S. Department of Energy
      (DOE) as prime lignocellulosic feedstock as it produces record biomass yields and
      is able to grow on low-value land with reduced inputs. Molecular improvement of
      energy cane is an essential step toward the development of a high-value crop and
      may contribute to improved biomass conversion to value added products. Such
      improvements require a development of an efficient regeneration and
      transformation system for the vegetatively propagated energy cane varieties. In
      this report, an efficient biolistic gene delivery protocol for energy canes
      (genotype L 79-1002 and Ho 00-961) has been established with immature leaf rolls
      as explants. Embryonic calli, developed approximately 6 weeks after culture
      initiation and was used as target for biolistic transfer of a minimum expression
      cassette of P-ubi::nptII::35S polyA derived from plasmid pJFNPTII. Putative
      transgenic clones of callus were obtained after selection on callus induction
      medium supplemented with 30 mg l(-1) geneticin. Regeneration was carried out on
      NB medium, which is modified from MS supplemented with 1.86 mg l(-1)
      naphthaleneacetic acid (NAA) and 0.1mg l(-1), 6- benzylaminopurine (BAP) and 20mg
      l(-1) paromomycin. Shoots growing on selection media were transferred to hormone
      free medium with 20 mg l(-1) paromomycin. Putative transgenic lines were first
      analyzed by PCR. Transgene integration was confirmed by Southern blot analysis.
      ELISA (Enzyme-Linked Immunosorbent Assay) and Immunochromathography assays
      confirmed transgene expression. 

PMID- 25751172
TI  - Inhibitory mechanisms of CME-1, a novel polysaccharide from the mycelia of
      Cordyceps sinensis, in platelet activation.
AB  - OBJECTIVE: CME-1 is a polysaccharide purified from the mycelia of medicinal
      mushroom Cordyceps sinensis, its molecular weight was determined to be 27.6 kDa
      by using nuclear magnetic resonance and gas chromatography-mass spectrometry. The
      initiation of arterial thromboses is relevant to various cardiovascular diseases
      (CVDs) and is believed to involve platelet activation. Our recent study exhibited
      that CME-1 has potent antiplatelet activity via the activation of adenylate
      cyclase/cyclic AMP ex vivo and in vivo. METHODS: The aggregometry, and
      immunoblotting were used in this study. RESULTS: In this study, the mechanisms of
      CME-1 in platelet activation is further investigated and found that CME-1
      inhibited platelet aggregation as well as the ATP-release reaction, relative
      intracellular [Ca(+2)] mobilization, and the phosphorylation of phospholipase C
      (PLC)gamma2 and protein kinase C (PKC) stimulated by collagen. CME-1 has no
      effects on inhibiting either convulxin, an agonist of glycoprotein VI, or
      aggretin, an agonist of integrin alpha2beta1 stimulated platelet aggregation.
      Moreover, this compound markedly diminished thrombin and arachidonic acid (AA)
      induced phosphorylation of p38 mitogen-activated protein kinase (MAPK),
      extracellular signal-regulated kinase 2, c-Jun N-terminal kinase 1, and Akt.
      Treatment with SQ22536, an inhibitor of adenylate cyclase, markedly diminished
      the CME-1-mediated increasing of cyclic AMP level and reversed prostaglandin E1-
      or CME-1-mediated inhibition of platelet aggregation and p38 MAPK and Akt
      phosphorylation stimulated by thrombin or AA. Furthermore, phosphodiesterase
      activity of human platelets was not altered by CME-1. CONCLUSION: The crucial
      finding of this study is that the antiplatelet activity of CME-1 may initially
      inhibit the PLCgamma2-PKC-p47 cascade, and inhibit PI3-kinase/Akt and MAPK
      phosphorylation through adenylate cyclase/ cyclic AMP activation, then inhibit
      intracellular [Ca(+2)] mobilization, and, ultimately, inhibit platelet
      activation. The novel role of CME-1 in antiplatelet activity indicates that this
      compound exhibits high therapeutic potential for treating or preventing CVDs.

PMID- 25751173
TI  - Primary characterization and evaluation of anti ulcerogenic activity of an
      aqueous extract from callus culture of Cereus peruvianus Mill. (Cactaceae).
AB  - In the current study we reported cultivation, extraction procedure, analysis and
      preliminary characterization of the aqueous extract from Cereus peruvianus callus
      culture and evaluated its anti ulcerogenic activity in vivo models of
      experimental ulcers in Wistar rats. The obtained aqueous extract from callus (AC)
      was dialyzed and subjected to freeze-thaw process, providing a possible
      polysaccharide. The carbohydrate and protein contents of the aqueous extract were
      estimated at 53.4% and 0.66%, respectively, composed primarily of galactose,
      arabinose and galacturonic acid, with minor amounts of glucose. This appeared
      heterogeneous when analyzed by high-performance size-exclusion chromatography and
      a multiangle laser light scattering detector (HPSEC-MALLS). The AC was found to
      be significantly effective against ethanol-induced lesions but was ineffective
      against indomethacin-induced lesions. The callus culture of C. peruvianus is an
      alternative source for the synthesis of substances originally produced by plants.
      The calluses grown indefinitely in vitro under controlled conditions are stable
      tissues, and the aqueous extract from calluses may be used instead of fully
      developed plants using the protocols described in this study.

PMID- 25751170
TI  - Amyloid beta-protein assembly: The effect of molecular tweezers CLR01 and CLR03.
AB  - The early oligomerization of amyloid beta-protein (Abeta) has been shown to be an
      important event in the pathology of Alzheimer's disease (AD). Designing small
      molecule inhibitors targeting Abeta oligomerization is one attractive and
      promising strategy for AD treatment. Here we used ion mobility spectrometry
      coupled to mass spectrometry (IMS-MS) to study the different effects of the
      molecular tweezers CLR01 and CLR03 on Abeta self-assembly. CLR01 was found to
      bind to Abeta directly and disrupt its early oligomerization. Moreover, CLR01
      remodeled the early oligomerization of Abeta42 by compacting the structures of
      dimers and tetramers and as a consequence eliminated higher-order oligomers.
      Unexpectedly, the negative-control derivative, CLR03, which lacks the hydrophobic
      arms of the tweezer structure, was found to facilitate early Abeta
      oligomerization. Our study provides an example of IMS as a powerful tool to study
      and better understand the interaction between small molecule modulators and Abeta
      oligomerization, which is not attainable by other methods, and provides important
      insights into therapeutic development of molecular tweezers for AD treatment.

PMID- 25751166
TI  - The role of vascular endothelial growth factor in neurodegeneration and cognitive
      decline: exploring interactions with biomarkers of Alzheimer disease.
AB  - IMPORTANCE: A subset of older adults present post mortem with Alzheimer disease
      (AD) pathologic features but without any significant clinical manifestation of
      dementia. Vascular endothelial growth factor (VEGF) has been implicated in
      staving off AD-related neurodegeneration. OBJECTIVE: To evaluate whether VEGF
      levels are associated with brain aging outcomes (hippocampal volume and
      cognition) and to further evaluate whether VEGF modifies relations between AD
      biomarkers and brain aging outcomes. DESIGN, SETTING, AND PARTICIPANTS: Biomarker
      analysis using neuroimaging and neuropsychological outcomes from the Alzheimer's
      Disease Neuroimaging Initiative. This prospective longitudinal study across North
      America included individuals with normal cognition (n = 90), mild cognitive
      impairment (n = 130), and AD (n = 59) and began in October 2004, with follow-up
      ongoing. MAIN OUTCOMES AND MEASURES: Cerebrospinal fluid VEGF was cross
      sectionally related to brain aging outcomes (hippocampal volume, episodic memory,
      and executive function) using a general linear model and longitudinally using
      mixed-effects regression. Alzheimer disease biomarker (cerebrospinal fluid beta
      amyloid 42 and total tau)-by-VEGF interactions evaluated the effect of VEGF on
      brain aging outcomes in the presence of enhanced AD biomarkers. RESULTS: Vascular
      endothelial growth factor was associated with baseline hippocampal volume (t277 =
      2.62; P = .009), longitudinal hippocampal atrophy (t858 = 2.48; P = .01), and
      longitudinal decline in memory (t1629 = 4.09; P < .001) and executive function
      (t1616 = 3.00; P = .003). Vascular endothelial growth factor interacted with tau
      in predicting longitudinal hippocampal atrophy (t845 = 4.17; P < .001), memory
      decline (t1610 = 2.49; P = .01), and executive function decline (t1597 = 3.71; P
      < .001). Vascular endothelial growth factor interacted with beta-amyloid 42 in
      predicting longitudinal memory decline (t1618 = -2.53; P = .01). CONCLUSIONS AND
      RELEVANCE: Elevated cerebrospinal fluid VEGF was associated with more optimal
      brain aging in vivo. The neuroprotective effect appeared strongest in the
      presence of enhanced AD biomarkers, suggesting that VEGF may be particularly
      beneficial in individuals showing early hallmarks of the AD cascade. Future work
      should evaluate the interaction between VEGF expression in vitro and pathologic
      burden to address potential mechanisms.

PMID- 25751174
TI  - The facilitatory effect of Casearia sylvestris Sw. (guacatonga) fractions on the
      contractile activity of mammalian and avian neuromuscular apparatus.
AB  - Many natural products influence neurotransmission and are used clinically. In
      particular, facilitatory agents can enhance neurotransmission and are potentially
      useful for treating neuromuscular diseases in which muscular weakness is the
      major symptom. In this work, we investigated the facilitatory effect of apolar to
      polar fractions of Casearia sylvestris Sw. (guacatonga) on contractility in mouse
      phrenic nerve-diaphragm (PND) and chick biventer cervicis (BC) neuromuscular
      preparations exposed to indirect (via the nerve; 3 V stimuli) and direct (30 V
      stimuli) muscle stimulation in the absence and presence of pharmacological
      antagonists. Methanolic and ethyl acetate fractions, but not hexane or
      dichloromethane fractions, exerted a facilitatory effect on PND (indirect
      stimulation). The methanolic fraction was chosen for further assays to assess the
      involvement of: 1) presynaptic sites (axons or nerve terminals), 2) postsynaptic
      sites (cholinergic receptors, sarcolemma or T-tubules), and 3) the synaptic cleft
      (acetylcholinesterase enzyme). In preparations treated with d-tubocurarine, the
      methanolic fraction did not cause facilitation in response to direct stimuli;
      this fraction was also unable to reverse dantrolene-induced blockade (indirect
      stimulation). In curarized preparations, the methanolic fraction either restored
      neuromuscular transmission (mimicking the effect of neostigmine) or failed to
      cause any recovery of neurotransmission. In the presence of 3,4-diaminopyridine
      (3,4-DAP), the methanolic fraction decreased twitch amplitude, whereas at a high
      frequency of stimulation (40 Hz) there was an increase in tetanic tension. In BC
      preparations, the methanolic fraction did not affect contractures to exogenous
      acetylcholine or potassium chloride. Incubation with atropine showed there was
      certain modulation by prejunctional nicotinic receptors, whereas treatment with
      nifedipine showed that the neurofacilitation required the entry of extracellular
      calcium. Tetrodotoxin did not prevent the facilitatory effect of 3,4-DAP or
      neostigmine, but antagonized the response to the methanolic fraction. These
      findings indicate that neuronal sodium channels have an important role in the
      facilitatory response to the methanolic fraction, with extracellular calcium
      entry via calcium channels modulating this neurofacilitation. Possible modulation
      of prejunctional cholinoceptors was not excluded, particularly in view of certain
      antagonism by the methanolic fraction at muscarinic receptors. Since facilitation
      by the methanolic fraction involved enhanced acetylcholine release, use of this
      fraction could be potentially beneficial in neuromuscular diseases and in the
      reversal of residual paralysis in the post-operative period or after local
      anaesthesia. 

PMID- 25751175
TI  - Electrocatalyst on insulating support?: Hollow silica spheres loaded with Pt
      nanoparticles for methanol oxidation.
AB  - Electrocatalytic oxidation of methanol on silica hollow spheres, loaded with
      platinum nanoparticles (Pt-SiO2-HS), is reported. The functionalized hollow
      silica spheres were prepared by the surfactant (lauryl ester of tyrosine)
      template-assisted synthesis. These spheres were loaded with platinum
      nanoparticles by gamma-radiolysis. Energy-dispersive X-ray analysis (EDAX) and X
      ray photoelectron spectroscopy (XPS) analyses confirmed presence of Si and Pt in
      the composite. High-resolution transmission electron microscopy showed the
      formation of uniformly deposited Pt nanoparticles over the hollow spheres with a
      predominant Pt(111) lattice plane on the surface. In spite of the poor conducting
      nature of the silica support, the oxidation potential and current density per
      unit mass for methanol oxidation were noted to be ca. 0.72 V vs NHE and 270 mA
      mg(-1), respectively, which are among the best values reported in its class. The
      composite did not show any sign of a degradation even after repeated use. In
      fact, the anodic current was found to increase under constant polarization, which
      is attributed to a facile reaction between adsorbed CO with a surface hydroxyl
      group present on the silica support. These results are in favor of Pt-SiO2-HS as
      a promising electrocatalyst material in the direct methanol fuel cell (DMFC)
      applications. 

PMID- 25751176
TI  - Effects of preventive family service coordination for parents with mental
      illnesses and their children, a RCT.
AB  - Children of parents with a mental illness (COPMI) are at increased risk for
      developing psychiatric disorders, especially when parenting is compromised by
      multiple risk factors. Due to fragmented services, these families often do not
      get the support they need. Can coordination between services, as developed in the
      Preventive Basic Care Management (PBCM) program, improve parenting and prevent
      child behavioral problems? This randomized controlled clinical trial (RCT)
      compared the effectiveness of PBCM with a control condition. Ninety-nine
      outpatients of a community mental health center were randomized to intervention
      or control. Primary outcomes included parenting quality (assessed by the HOME
      instrument), parenting skills (parenting skills subscale of FFQ), and parenting
      stress (PDH). Secondary outcomes are child behavioral problems (SDQ). Outcomes
      were assessed at baseline and after 9 and 18 months. Effects were analyzed by
      Repeated Measures Analysis of Variance. Most families were single-parent families
      belonging to ethnic minorities. The results of the first RCT on effects of PBCM
      suggest that this intervention is feasible and has a positive effect on parenting
      skills. There was no evidence for effects on the quality of parenting and
      parenting stress, nor preventive effects on child behavioral problems.
      Replication studies in other sites, with more power, including monitoring of the
      implementation quality and studying a broader palette of child outcomes are
      needed to confirm the positive effects of PBCM. Long-term prospective studies are
      needed to investigate if improved parenting skills lead to positive effects in
      the children in the long run.

PMID- 25751178
TI  - Reflections.
AB  - Times that prompt reflection include anniversaries, deaths, and birthday
      celebrations. September 2014, Donald A. Bloch, MD died. He started this Journal
      (formerly Family Systems Medicine) and the Collaborative Family Health Care
      Association (formerly Coalition). Don's death occurred just one month before CFHA
      celebrated its 20th year. In this issue and our June issue, Families, Systems and
      Health devotes space for reflection. We begin with a remembrance of Don, written
      by his friend, mentee, and colleague, David Seaburn, PhD, LMFT. We also reflect
      on the 20th annual CFHA meeting, where we could see Don's vision at work in the
      plenaries. In our June issue we will publish a second article written by CJ Peek,
      PhD, about Don's vision of the field, the organization (CFHA), and this Journal.
      The article will ask readers to reflect.

PMID- 25751177
TI  - Clinician perspectives on working with health coaches: A mixed methods approach.
AB  - We sought to understand how health coaches affect the work of primary care
      clinicians and influence their perception of patient care. As a mixed methods
      hypothesis-generating study, we administered a structured post-visit survey and
      conducted in-depth individual interviews with primary care clinicians who worked
      with health coaches at two urban community health centers. Survey responses were
      compared using t tests. Interviews were transcribed and analyzed using Atlas.ti
      software and modified grounded theory. Surveys were completed by 15 of 17
      clinicians for 61% of eligible patient visits (269/441). Compared to usual care
      patients, clinicians rated visits with health-coached patients as less demanding
      (2.44 vs. 3.06, p < .001) and were more likely to feel that they had adequate
      time with their patient (3.96 vs. 3.57, p < .001). Qualitative findings expanded
      upon these results and uncovered four key health coach activities thought to
      improve patient care. Through developing a rapport with patients over time and
      working with patients between medical visits, health coaches (a) empower patients
      by offering self-management support, (b) bridge communication gaps between
      clinicians and patients, (c) assist patients in navigating the health care
      system, and (d) act as a point of contact for patients.

PMID- 25751179
TI  - Donald A. Bloch, MD: a remembrance.
AB  - When someone dies, the world, or at least a representative portion of it, should
      stop, take note, weep, give thanks, and then measure the influence of that life
      on those it has touched so that moving forward is made more meaningful. This
      article takes a moment to remember Donald A. Bloch, MD. Bloch was a visionary and
      an innovator who chose collaboration as his primary methodology for creating
      change. He introduced us to the "dual optic," in which "Dr. Biomedicine" and "Dr.
      Psychosocial" work hand in hand with the patient and family. In addition to being
      a visionary, Don was an "architect/urban planner", who helped build communities
      and coalitions that promoted new ideas and championed novel initiatives. He was
      one of the founders of Family Systems Medicine (now Families, Systems, and
      Health), which is the field's vanguard journal.

PMID- 25751180
TI  - Another list or a grounding tool? Thoughts on the Q-List Manifesto.
AB  - Comments on the article by William B. Ventres (see record 2015-01771-001). This
      article discusses the Q-List Manifesto and how it differs from The Checklist
      Manifesto for procedural medicine. Is the question list any different from a
      checklist? What might it add and what pitfalls might it face if implemented? The
      Q-List can be useful for learners, from medical student to resident, a reminder
      to check in with patients, themselves and the domains, like Daily Reality,
      Patient Focus, and Practitioner Focus. It offers a framework along with concrete
      questions to explore with the patient, their families, and oneself.

PMID- 25751181
TI  - Response to Dr. Ventres' Q-List Manifesto.
AB  - Comments on the article by William B. Ventres (see record 2015-01771-001). Dr.
      Ventres' article clearly defines why a checklist approach that is appropriate to
      procedurally oriented specialties is often not appropriate in primary care. For
      those of us in primary care who felt uneasy about a checklist approach, it is a
      welcome reflection on some of the underlying reasons for that unease.

PMID- 25751190
TI  - Reconstruction of a traumatic plantar foot defect with a novel free flap: The
      medial triceps brachii free flap.
AB  - INTRODUCTION: Lower extremity defects may account for 14.6% of the approximately
      117 million visits to emergency departments in the U. S. in 2007. In this
      article, we present a reconstruction of a traumatic plantar foot defect with a
      medial triceps brachii (MTB) free flap. CLINICAL CASE: A 53-year-old man
      sustained an accidental gunshot wound to the right foot. The patient was admitted
      after the failure of a sural flap procedure performed in another hospital. He
      presented with a soft-tissue defect with calcaneal exposition and osteomyelitis.
      The defect was reconstructed with a MTB free flap anastomosed to his dorsalis
      pedis vessels. RESULTS: Flap raising time was 52 min. There were no
      intraoperative complications. The total flap surface was 38.5 cm2. The pedicle
      length was 3 cm. The diameters of the artery and vein of the flap pedicle were
      1.1 mm and 1.4 mm, respectively. Ischemia time was 28 min. His donor site healed
      uneventfully without any morbidity, and the scar was well concealed. The flaps
      survived and there was no partial flap necrosis. A split-thickness skin graft was
      performed 12 days postoperatively. Two months later, he had a completely healed
      wound with no contour abnormality. The total follow-up was 24 months. The patient
      was able to walk normally. CONCLUSION: MTB free flap appears to be an excellent
      option for plantar foot defects in patients with preserved vascularization of the
      foot. Due to the anatomical shape of the flap, the position of its pedicle, and
      the moldability of the muscle, we predict that the use of the MTB free flap will
      grow and develop rapidly for reconstruction of ankle and foot defects.

PMID- 25751191
TI  - Methylation status of the chromosome arm 19q MicroRNA cluster in sporadic and
      androgenetic-Biparental mosaicism-associated hepatic mesenchymal hamartoma.
AB  - The C19MC gene on chromosome band 19q13.4 encodes a cluster of 46 microRNAs;
      those microRNAs are normally only expressed from the paternal allele and in the
      placenta. Placental expression correlates with selective demethylation of the
      paternal C19MC promoter, in contrast to methylation of both maternal and paternal
      alleles in nonplacental tissues. Prior investigations demonstrated "ectopic"
      activation of this gene in most hepatic mesenchymal hamartomas, including
      sporadic tumors and others with androgenetic-biparental mosaicism (subset of
      cells are diploid, but contain only paternally derived chromosomes). In the
      present investigation of C19MC promoter methylation status in a series of 14
      mesenchymal hamartomas, a demethylated allele was identified in 6 tumors,
      including all 4 with androgenetic-biparental mosaicism. Conversely, only
      methylated alleles were cloned from sporadic hamartomas, including 3 tumors with
      chromosomal rearrangements thought likely to activate C19MC expression
      independent of the native promoter. In conjunction with published data, the
      findings suggest multiple molecular mechanisms for C19MC activation in hepatic
      mesenchymal hamartoma, including the existence of a normal placental imprinting
      pattern in mesenchymal cells in a subset of cases. Some or all of the latter
      hamartomas may result from placental "grafting," a hypothesis supported by
      endothelial expression of the placental vascular marker, glucose transporter-1,
      in 1 of the 6 cases with a demethylated allele. 

PMID- 25751193
TI  - Exploring the relationship between fear of cancer recurrence and sleep quality in
      cancer survivors.
AB  - Fear of cancer recurrence (FCR) and sleep disturbance are identified as top
      psychosocial concerns in cancer survivorship, yet few studies have explored the
      association between these two factors. Using data from a study of 67 cancer
      survivors, hierarchical logistic regression models examined the relationships
      between socio-demographic characteristics, FCR, and sleep disturbance. More than
      half of survivors reported poor sleep quality; those with some college education
      and those with higher levels of FCR were at greater risk for poor sleep. These
      findings provide formative data for oncology social workers to implement
      interventions that target FCR as a strategy for improving sleep. 

PMID- 25751194
TI  - Bolstering medical education to enhance critical care capacity in Cambodia.
AB  - The capacity to care for the critically ill has long been viewed as a fundamental
      element of established and comprehensive health care systems. Extending this
      capacity to health care systems in low- and middle-income countries is important
      given the burden of disease in these regions and the significance of critical
      care in overall health system strengthening. However, many practicalities of
      improving access and delivery of critical care in resource-limited settings have
      yet to be elucidated. We have initiated a program to build capacity for the care
      of critically ill patients in one low-income Southeast Asian country, Cambodia.
      We are leveraging existing international academic partnerships to enhance
      postgraduate critical care education in Cambodia. After conducting a needs
      assessment and literature review, we developed a three-step initiative targeting
      training in mechanical ventilation. First, we assessed and revised the current
      resident curriculum pertaining to mechanical ventilation. We addressed gaps in
      training, incorporated specific goals and learning objectives, and decreased the
      hours of lectures in favor of additional bedside training. Second, we are
      incorporating e-learning, e-teaching, and e-assessment into the curriculum, with
      both live, interactive and independent, self-paced online instruction. Third, we
      are developing a train-the-trainer program defined by bidirectional international
      faculty exchanges to provide hands-on, case-based, and bedside training to
      achieve competency-based outcomes. In targeting specific educational needs and a
      key population-the next generation of Cambodian intensivists-this carefully
      designed approach should address some existing gaps in the health care system and
      hopefully yield a lasting impact. 

PMID- 25751195
TI  - Septic abortion with placenta accreta in pregnancy after endometrial ablation.
AB  - BACKGROUND: Pregnancy after endometrial ablation is a rare event, occurring in
      approximately 0.7% of cases. When it occurs, serious complications may be
      anticipated for both mother and fetus, including abnormal placentation.
      Termination of pregnancy in these cases is a challenging issue, made more so by
      the lack of availability of these services. CASE: We report a case of pregnancy
      after endometrial ablation complicated by placenta accreta. Initiation of a
      second-trimester termination procedure with lethal fetal injection resulted in
      subsequent septic abortion necessitating abdominal hysterectomy. CONCLUSION:
      Pregnancy after endometrial ablation is a rare and potentially morbid event.
      Patients should be counseled about the necessity of contraception at the time of
      endometrial ablation. Termination should be approached with caution and requires
      the availability of skilled providers.

PMID- 25751196
TI  - Bowel perforation after placement of tubal occlusion contraceptive.
AB  - BACKGROUND: The tubal occlusion contraceptive provides a hysteroscopic technique
      for female sterilization. Efficacy of the tubal occlusion contraceptive relies on
      proper placement within the proximal aspect of the fallopian tubes. As long-term
      data become available, rates of complications are better defined. CASE: This is a
      case of a patient who underwent placement of a tubal occlusion contraceptive. As
      a result of persistent pain and nausea, imaging was performed and malposition of
      the tubal occlusion contraceptive was identified. During laparoscopy, bowel
      perforation at the terminal ileum was diagnosed. Laparoscopic ileocecectomy was
      performed. CONCLUSION: There should be a low threshold for evaluation of
      complications after tubal occlusion contraceptive placement. Although rare, bowel
      perforation after placement of the tubal occlusion contraceptive can occur.
      Laparoscopic management should be considered.

PMID- 25751197
TI  - Racial disparities in treatment of high-grade endometrial cancer in the Medicare
      population.
AB  - OBJECTIVE: To examine the patterns of care and survival for African American and
      white women with high-grade endometrial cancer. METHODS: The linked Surveillance,
      Epidemiology, and End Results and Medicare databases were queried to identify
      patients diagnosed with grade 3 endometrioid endometrial adenocarcinoma, uterine
      carcinosarcoma, uterine clear cell carcinoma, and uterine serous carcinoma
      between 1992 and 2009. The effect of treatment modality on survival was analyzed
      using the Kaplan-Meier method. Factors predictive of outcome were compared using
      the Cox proportional hazards model. RESULTS: A total of 9,042 patients met study
      eligibility criteria. African Americans had definitive surgery (76.8% compared
      with 88.7%; P<.001) less frequently. There was no difference in the rate of
      adjuvant treatment between the groups. In the crude models for both all-cause
      mortality and cancer-specific mortality, African American women had an increased
      overall and disease-specific hazard of death compared with white women. The
      overall hazard ratio for African American women was 1.6 (95% confidence interval
      [CI] 1.5-1.7), and the disease-specific hazard ratio was 1.5 (95% CI 1.3-1.6).
      Over the entire study period, after adjusting for stage, age, period of
      diagnosis, registry region, urban compared with rural setting, marital status,
      treatment, surgery, socioeconomic status, and comorbidities, there was no
      association between race and lower disease-specific survival (hazard ratio 1.1,
      95% CI 1-1.2; P=.06). CONCLUSION: African American women had lower cancer
      specific and all-cause survival compared with white women. Controlling for
      treatment, sociodemographics, comorbidities, and histopathologic variables
      eliminated the difference between African American and white women in the disease
      specific analysis.

PMID- 25751198
TI  - Oral and intramuscular treatment options for early postpartum endometritis in low
      resource settings: a systematic review.
AB  - OBJECTIVE: To suggest options for oral and intramuscular antibiotic treatment of
      early postpartum endometritis in low-resource community settings where
      intravenous antibiotics are unavailable. DATA SOURCES: Studies were identified
      through MEDLINE from inception through December 2014. Search terms included
      [("anti-bacterial agents [MeSH]" or "anti-infective agents [MeSH]") and
      ("endometritis [MeSH]" or "puerperal infection [MeSH]")]. A second search using
      the terms [("endometritis or endomyometritis or puerperal infection) and
      ("antibiotics or antimicrobials or anti-bacterial agents or anti-infective
      agents)"] was also used. Additionally, all references from selected articles were
      reviewed, a hand-search of a subject matter expert library was conducted, and a
      search of ClinicalTrials.gov was performed. METHODS OF STUDY SELECTION: We
      conducted a systematic review of the literature in two phases. Phase I provides a
      summary of clinical cure data from prospective studies of oral and intramuscular
      antimicrobial regimens as well as summarizes evidence from trials of intravenous
      antimicrobials. Phase II is a quantitative analysis of pathogens from
      intrauterine postpartum endometritis samples. Based on these results, and with
      consideration of existing recommendations for antibiotic use during
      breastfeeding, we suggest oral and intramuscular antimicrobial options for the
      treatment of early postpartum endometritis after vaginal delivery in low-resource
      settings. TABULATION, INTEGRATION, AND RESULTS: Reports involving oral or
      intramuscular antimicrobial treatment of postpartum endometritis are rare and of
      generally poor quality. Antimicrobial trials of postpartum endometritis treatment
      and intrauterine microbiology studies suggest five antimicrobial regimens may be
      effective: oral clindamycin plus intramuscular gentamicin, oral amoxicillin
      clavulanate, intramuscular cefotetan, intramuscular meropenem or imipenem
      cilastatin, and oral amoxicillin in combination with oral metronidazole.
      CONCLUSION: This review provides suggestions for oral, intramuscular, and
      combined antimicrobial regimens that may warrant additional study. Experimental
      trials should consider clinical effectiveness, safety and side effects profiles,
      and feasibility of community-based treatment.

PMID- 25751199
TI  - Contraceptive efficacy, safety, fit, and acceptability of a single-size diaphragm
      developed with end-user input.
AB  - OBJECTIVE: To estimate contraceptive efficacy, safety, acceptability, and fit of
      a single-size diaphragm used with contraceptive gel. METHODS: We conducted a
      multicenter trial in which 450 couples used the single-size diaphragm, 300
      randomized to acid-buffering gel and 150 to nonoxynol-9, for at least 190 days
      and six menstrual cycles. Visits were at enrollment and after menstrual cycles 1,
      3, and 6. Study outcomes included pregnancy probability, safety, acceptability,
      and fit. Pregnancy and safety were compared with an historical control group who
      used a standard diaphragm with these gels. RESULTS: Most (439/450 [98%]) women
      could be fitted with the single-size diaphragm. A total of 421 of 450 (94%)
      provided follow-up. The 35 study pregnancies yielded 6-month Kaplan-Meier
      cumulative typical use pregnancy probabilities per 100 women with 95% confidence
      intervals (CIs) of 10.4 (6.9-14.0) for all users and 9.6 (5.5-13.6) and 12.5 (5.4
      19.5) with acid-buffering gel and nonoxynol-9, respectively. Historical control
      analysis yielded a propensity score-adjusted estimate of this pregnancy
      probability for the single-size diaphragm of 11.3 compared with 10.7 per 100
      women for the standard diaphragm ([rounded] difference 0.7, 95% CI -3.6 to 4.9).
      Approximately half (51%) reported at least one urogenital event but compared
      favorably to the standard diaphragm in historical control analysis. Most (282/342
      [82%]) liked the diaphragm. Results suggest that if provided by a clinician, 94%
      (95% CI 92-96%) could insert, correctly position, and remove the diaphragm.
      CONCLUSION: The single-size diaphragm was safe, as effective as a standard
      diaphragm, and acceptable when used with contraceptive gel. CLINICAL TRIAL
      REGISTRATION: ClinicalTrials.gov, www.clinicaltrials.gov, NCT00578877.

PMID- 25751200
TI  - Sociodemographic disparities in advanced ovarian cancer survival and adherence to
      treatment guidelines.
AB  - OBJECTIVE: To estimate whether race or ethnic and socioeconomic strata are
      independently associated with advanced-stage ovarian cancer-specific survival
      after adjusting for adherence to National Comprehensive Cancer Network treatment
      guidelines. METHODS: The design was a retrospective population-based cohort study
      of patients with stage IIIC-IV epithelial ovarian cancer identified from the
      Surveillance, Epidemiology, and End Results-Medicare database (1992-2009).
      Quartile of census tract median household income was used as the measure of
      socioeconomic status (quartiles 1-4). A multivariable logistic regression model
      was used to identify characteristics predictive of adherence to National
      Comprehensive Cancer Network guidelines for surgery and chemotherapy. Cox
      proportional hazards models and propensity score matching were used for survival
      analyses. RESULTS: A total of 10,296 patients were identified, and 30.2% received
      National Comprehensive Cancer Network guideline-adherent care. Among demographic
      variables, black race (adjusted odds ratio [OR] 1.53, 95% confidence interval
      [CI] 1.22-1.92) and low socioeconomic status (quartile 1, adjusted OR 1.32, 95%
      CI 1.14-1.52) were independently associated with nonguideline care. Stratified
      multivariate survival analysis using the propensity score-matched sample
      (n=5,124) revealed that deviation from treatment guidelines was associated with a
      comparable risk of disease-related death across race-ethnicity: whites (adjusted
      hazard ratio [HR] 1.59, 95% CI 1.48-1.71), blacks (adjusted HR 1.66, 95% CI 1.19
      2.30), Asian or Pacific Islanders (adjusted HR 1.52, 95% CI 0.99-1.92), and
      Hispanics (adjusted HR 1.91, 95% CI 0.98-3.72). Across socioeconomic status,
      deviation from treatment guidelines was also associated with a comparable risk of
      ovarian cancer mortality for quartile 1 (adjusted HR 1.69, 95% CI 1.47-1.95),
      quartile 2 (adjusted HR 1.63, 95% CI 1.42-1.87), quartile 3 (adjusted HR 1.51,
      95% CI 1.32-1.73), and quartile 4 (adjusted HR 1.57, 95% CI 1.38-1.79).
      CONCLUSION: Adherence to treatment guidelines for advanced-stage ovarian cancer
      is associated with equivalent survival benefit across racial or ethnic and
      socioeconomic strata. Ensuring equal access to standard treatment is a viable
      strategic approach to reduce survival disparities.

PMID- 25751201
TI  - Placenta accreta and vaginal bleeding according to gestational age at delivery.
AB  - OBJECTIVE: To evaluate the incidence of vaginal bleeding in women with placenta
      accreta according to gestational age at delivery. METHODS: This is a
      retrospective cohort study of women with prior cesarean delivery and persistent
      placenta previa delivered at our institution between December 1997 and December
      2011. Diagnosis of invasion was based on hysterectomy performed for an abnormally
      adherent placenta with histologic confirmation. Suspicion for invasion was based
      on the impression of the attending physician at the time of ultrasonography.
      Records were reviewed to identify indication for delivery and estimated blood
      loss. Statistical analyses were performed using Student's t test, chi2 test, and
      Mantel-Haenszel and Jonckheere-Terpstra tests for trend. RESULTS: Of 216 women
      with prior cesarean delivery and persistent previa, 65 (30%) required cesarean
      hysterectomy and had histologic confirmation of invasion. Urgent delivery for
      bleeding was performed in 20% of these pregnancies (13/65). Delivery for bleeding
      decreased significantly with advancing gestation (P=.001). In our series, 71%
      with accreta were delivered at 36 weeks of gestation or greater with delivery for
      bleeding in five (11%), and estimated blood loss was not increased in these
      pregnancies. Of 79 women with ultrasonographic suspicion for accreta, the
      incidence of vaginal bleeding prompting urgent delivery also decreased with
      advancing gestation (P<.001). CONCLUSION: Likelihood of vaginal bleeding
      necessitating delivery declined with advancing gestation in pregnancies with
      placenta accreta as did blood loss. Most were delivered at 36 weeks of gestation
      or greater, nearly 90% in the absence of bleeding complications. Thus, although
      preterm delivery is an important consideration when placenta accreta is
      suspected, our findings support individualizing delivery planning.

PMID- 25751202
TI  - Contribution of placenta accreta to the incidence of postpartum hemorrhage and
      severe postpartum hemorrhage.
AB  - OBJECTIVE: To quantify the contribution of placenta accreta to the rate of
      postpartum hemorrhage and severe postpartum hemorrhage. METHODS: All hospital
      deliveries in Canada (excluding Quebec) for the years 2009 and 2010 (N=570,637)
      were included in a retrospective cohort study using data from the Canadian
      Institute for Health Information. Placenta accreta included placental adhesion to
      the uterine wall, musculature, and surrounding organs (accreta, increta, or
      percreta). Severe postpartum hemorrhage included postpartum hemorrhage with blood
      transfusion, hysterectomy, or other procedures to control bleeding (including
      uterine suturing and ligation or embolization of pelvic arteries). Rates, rate
      ratios, population-attributable fractions (ie, incidence of postpartum hemorrhage
      attributable to placenta accreta), and 95% confidence intervals (CIs) were
      estimated. Logistic regression was used to quantify associations between placenta
      accreta and risk factors. RESULTS: The incidence of placenta accreta was 14.4
      (95% CI 13.4-15.4) per 10,000 deliveries (819 cases among 570,637 deliveries),
      whereas the incidence of placenta accreta with postpartum hemorrhage was 7.2 (95%
      CI 6.5-8.0) per 10,000 deliveries. Postpartum hemorrhage among women with
      placenta accreta was predominantly third-stage hemorrhage (41% of all cases).
      Although placenta accreta was strongly associated with postpartum hemorrhage
      (rate ratio 8.3, 95% CI 7.7-8.9), its low frequency resulted in a small
      population-attributable fraction (1.0%, 95% CI 0.93-1.16). However, the strong
      association between placenta accreta and postpartum hemorrhage with hysterectomy
      (rate ratio 286, 95% CI 226-361) resulted in a population-attributable fraction
      of 29.0% (95% CI 24.3-34.3). CONCLUSION: Placenta accreta is too infrequent to
      account for the recent temporal increase in postpartum hemorrhage but contributes
      substantially to the proportion of postpartum hemorrhage with hysterectomy.

PMID- 25751203
TI  - Evaluation of third-degree and fourth-degree laceration rates as quality
      indicators.
AB  - OBJECTIVE: To examine the patterns and predictors of third-degree and fourth
      degree laceration in women undergoing vaginal delivery. METHODS: We identified a
      population-based cohort of women in the United States who underwent a vaginal
      delivery between 1998 and 2010 using the Nationwide Inpatient Sample.
      Multivariable log-linear regression models were developed to account for patient,
      obstetric, and hospital factors related to lacerations. Between-hospital
      variability of laceration rates was calculated using generalized log-linear mixed
      models. RESULTS: Among 7,096,056 women who underwent vaginal delivery in 3,070
      hospitals, 3.3% (n=232,762) had a third-degree laceration and 1.1% (n=76,347) had
      a fourth-degree laceration. In an adjusted model for fourth-degree lacerations,
      important risk factors included shoulder dystocia and forceps and vacuum
      deliveries with and without episiotomy. Other demographic, obstetric, medical,
      and hospital variables, although statistically significant, were not major
      determinants of lacerations. Risk factors in a multivariable model for third
      degree lacerations were similar to those in the fourth-degree model. Regression
      analysis of hospital rates (n=3,070) of lacerations demonstrated limited between
      hospital variation. CONCLUSION: Risk of third-degree and fourth-degree laceration
      was most strongly related to operative delivery and shoulder dystocia. Between
      hospital variation was limited. Given these findings and that the most modifiable
      practice related to lacerations would be reduction in operative vaginal
      deliveries (and a possible increase in cesarean delivery), third-degree and
      fourth-degree laceration rates may be a quality metric of limited utility.

PMID- 25751204
TI  - Association of health literacy with adherence to screening mammography
      guidelines.
AB  - OBJECTIVE: To investigate the relationship of health literacy and screening
      mammography. METHODS: All patients seen at a breast clinic underwent prospective
      assessment of health literacy from January 2010 to April 2013. All women at least
      40 years of age were included. Men and women diagnosed with breast cancer before
      age 40 years were excluded. Routine health literacy assessment was performed
      using the Newest Vital Sign. Demographic data were also collected. Medical
      records were reviewed to determine if patients had undergone screening
      mammography: women aged 40-49 years were considered to have undergone screening
      if they had another mammogram within 2 years. Women 50 years or older were
      considered to have undergone screening mammography if they had another mammogram
      within 1 year. RESULTS: A total of 1,664 consecutive patients aged 40 years or
      older were seen. No patient declined the health literacy assessment. Only 516
      (31%) patients had undergone screening mammography. Logistic regression analysis
      that included ethnicity, language, education, smoking status, insurance status,
      employment, income, and family history found that only three factors were
      associated with not obtaining a mammogram: low health literacy (odds ratio [OR]
      0.27, 95% confidence interval [CI] 0.19-0.37; P<.001), smoking (OR 0.64, 95% CI
      0.47-0.85; P=.002), and being uninsured (OR 0.66, 95% CI 0.51-0.85; P=.001).
      CONCLUSION: Of all the sociodemographic variables examined, health literacy had
      the strongest relationship with use of screening mammography.

PMID- 25751205
TI  - Lessons learned in pediatric clinical research to evaluate safe and effective use
      of drugs in pregnancy.
AB  - Children and pregnant women are vulnerable populations lacking clinical data to
      guide drug dosing. For children, over the past 15 years, the knowledge gap in
      pharmacokinetic, safety, and efficacy data has been narrowed as a result of the
      use of innovative clinical trial designs, minimal risk research methods,
      increased understanding of developmental pharmacology, multidisciplinary research
      teams, increased clinical pharmacology expertise and training, collaborative
      research networks, and critical legislative changes. This progress has not been
      observed to a similar degree for pregnant women. These two populations, however,
      share similar drug development challenges and, therefore, lessons learned in
      pediatric clinical trials can be leveraged to advance drug development in
      pregnant women. 

PMID- 25751206
TI  - Suicide risk among perinatal women who report thoughts of self-harm on depression
      screens.
AB  - OBJECTIVE: To estimate the incidence and clinical significance of suicidal
      ideation revealed during perinatal depression screening and estimate the
      associated suicide risk. METHODS: Retrospective cohort study of women completing
      the Edinburgh Postnatal Depression Scale at 24-28 weeks of gestation and 6 weeks
      postpartum through a suburban integrated health system with approximately 5,000
      annual deliveries on two hospital campuses. Suicidal ideation on the Edinburgh
      Postnatal Depression Scale and prediction of suicide risk were examined through
      multivariable modeling and qualitative analysis of clinical assessments. RESULTS:
      Among 22,118 Edinburgh Postnatal Depression Scale questionnaires studied,
      suicidal ideation was reported on 842 (3.8%, 95% confidence interval [CI] 3.5
      4.1%) and was positively associated with younger maternal age (antepartum mean
      age 30.9 compared with 31.9 years, P=.001), unpartnered relationship status
      (antepartum 29.5% compared with 16.5%, P<.001 and postpartum 25.0% compared with
      17.5%, P<.01), non-Caucasian race (antepartum 62.1% compared with 43.8%, P<.001
      and postpartum 62.4% compared with 45.2%, P<.001), non-English language
      (antepartum 11.0% compared with 6.6%, P<.001 and postpartum 12.4% compared with
      7.7%, P<.01), public insurance (antepartum 19.9% compared with 12.5%, P<.001 and
      postpartum 18.2% compared with 14.2%, P<.001), and preexisting psychiatric
      diagnosis (antepartum 8.4% compared with 4.2%, P<.001 and postpartum 12.0%
      compared with 5.8%, P<.001). Multivariable antepartum and postpartum models
      retained relationship status, language, relationship status by language
      interaction, and race; the postpartum model also found planned cesarean delivery
      negatively associated with suicidal ideation risk (odds ratio [OR] 0.56, 95% CI
      0.36-0.87) and severe vaginal laceration positively associated with suicidal
      ideation risk (OR 2.1, 95% CI 1.00-4.40). A qualitative study of 574 women
      reporting suicidal ideation indicated that 330 (57.5%, 95% CI 53.5-61.5%)
      experienced some degree of suicidal thought. Six patients (1.1%, 95% CI 0.2-1.9%)
      demonstrated active suicidal ideation with plan, intent, and access to means.
      Within this highest risk group, three patients reported a suicide attempt within
      the perinatal period. CONCLUSION: Among perinatal women screened for depression,
      3.8% reported suicidal ideation, but only 1.1% of this subgroup was at high risk
      for suicide. These findings support the need for systematic evaluation of those
      who report suicidal ideation to identify the small subset requiring urgent
      evaluation and care.

PMID- 25751207
TI  - Rationalizing definitions and procedures for optimizing clinical care and public
      health in fetal death and stillbirth.
AB  - Despite the recent focus on stillbirth, there remains a profound need to address
      problems associated with the definitions and procedures related to fetal death
      and stillbirth. The current definition of fetal death, first proposed in 1950,
      needs to be updated to distinguish between the timing of fetal death (which has
      etiologic and prognostic significance) and the timing of stillbirth (ie, the
      delivery of the dead fetus). Stillbirth registration procedures, modeled after
      live birth registration and not death registration, also need to be modernized
      because they can be an unnecessary burden on some grieving families. The problems
      associated with fetal death definitions and stillbirth-associated procedures are
      highlighted by selective fetal reduction in multifetal pregnancy; in many
      countries, the fetus reduced at 10-13 weeks of gestation and delivered at term
      gestation requires stillbirth registration and a burial permit even if fetal
      remains cannot be identified. An international consensus is needed to standardize
      the definition of reportable fetal deaths; ideally this should be based on the
      timing of fetal death and should address the status of pregnancy terminations. In
      this article, we list propositions for initiating an international dialogue that
      will rationalize fetal death definitions, registration criteria, and associated
      procedures, and thereby improve clinical care and public health. 

PMID- 25751208
TI  - Association between obesity and the trends of routes of hysterectomy performed
      for benign indications.
AB  - OBJECTIVE: To estimate the association between obesity and the recent trends of
      routes chosen for hysterectomy performed for benign indications in the United
      States. MATERIALS AND METHODS: Using the American College of Surgeons-National
      Surgical Quality Improvement Project's database, patients who underwent
      hysterectomy for benign indications from 2005 to 2011 were identified by
      International Classification of Diseases, 9th Revision codes and were categorized
      into total abdominal hysterectomy (TAH), total vaginal hysterectomy (TVH),
      laparoscopically assisted vaginal hysterectomy (LAVH), and total laparoscopic
      hysterectomy (TLH). The patients were divided into four subgroups according to
      body mass index (BMI) (less than 25, 25-29.9, 30-39.9, and 40 or greater). The
      data were analyzed using Student's t test or chi2 and Fisher's exact test.
      RESULTS: A total of 18,810 patients underwent hysterectomy for benign indications
      during the study period: 9,852 (52.4%) were TAH, 5,146 (27.4%) TVH, 2,296 (12.2%)
      LAVH, and 1,516 (8.0%) TLH. The rates of TAH increased from 45.7% in patients
      with ideal body weight to 62% in morbidly obese patients (P<.001). The rate of
      TVH and LAVH decreased from 32.7% and 13.3% in patients with ideal body weight to
      17.1% and 11.7% in morbidly obese patients, respectively (P<.001 and 0.04). The
      rate of TLH performed was independent of BMI (P=.61). Higher BMI was associated
      with longer operative time (P<.001) in all routes of hysterectomy. The rates of
      superficial and deep wound infections were higher with increasing BMI in patients
      undergoing TAH (P<.001) but not with TVH (P=.26), LAVH (P=1.0), or TLH (P=.48).
      CONCLUSION: Regarding hysterectomy performed for benign indications, increasing
      BMI was associated with increased rate of TAH and decreased rate of TVH and LAVH,
      but not the rate of TLH. Increasing BMI was associated with increased operative
      time for all subgroups and increased surgical site infection in the TAH group.

PMID- 25751209
TI  - Treatment for and clinical characteristics of granulomatous mastitis.
AB  - OBJECTIVE: To describe the clinical and paraclinical characteristics of
      idiopathic granulomatous mastitis, the management of our patients, and review the
      literature on this topic. METHODS: Patients referred to our clinic with a
      presumptive diagnosis of infectious mastitis were only included in the study if
      they had histopathologic confirmation of granulomatous mastitis. A systemic or
      infectious etiology was excluded by the testing of tissues and fluids by
      staining, culture, and polymerase chain reaction methods. Those patients with no
      reported etiology were categorized as idiopathic granulomatous mastitis and
      treated with antiinflammatory drugs. All were monitored for signs of recurrence.
      RESULTS: All 22 patients with a final diagnosis of idiopathic granulomatous
      mastitis were women with a mean age (+/- standard deviation) of 32.8 +/- 6.2
      years. Initial treatment with a prednisone regimen was given in 15 (68.2%)
      patients, prednisone plus methotrexate (MTX) in six (27.3%), and MTX alone in one
      (4.5%). Among the total of 22 patients with idiopathic granulomatous mastitis, 12
      (54.5%) received MTX either as an initial treatment or as an alternative regimen.
      Of the 22 patients, three (13.6%) had disease recurrence and four (18.2%)
      experienced adverse drug reactions. Sixteen (72.7%) patients discontinued the
      initial treatment regimen with acceptable control of disease activity and without
      recurrence or adverse drug reactions during the follow-up period. CONCLUSION:
      Idiopathic granulomatous mastitis is a distinct benign breast condition of
      unknown etiology but several triggers are suspected, including inflammatory,
      infectious, and hormonal factors. Corticosteroids and MTX, with or without
      surgery, are the treatment of choice in these patients.

PMID- 25751210
TI  - Association of isolated polyhydramnios at or beyond 34 weeks of gestation and
      pregnancy outcome.
AB  - OBJECTIVE: To evaluate pregnancy outcome among women with isolated polyhydramnios
      at admission for labor at or beyond 34 weeks of gestation. METHODS: Retrospective
      cohort study at a tertiary medical center between 2007 and 2012. Isolated
      polyhydramnios was defined as amniotic fluid index (AFI) greater than 25 cm at
      admission in the absence of gestational or pregestational diabetes mellitus or
      fetal structural or chromosomal anomalies. Women with isolated polyhydramnios
      were compared with women with a normal AFI (5-25 cm). RESULTS: Overall, 31,376
      women were eligible for analysis, of whom 215 (0.7%) had isolated polyhydramnios
      and 31,161 normal AFI. Women with isolated polyhydramnios had higher rates of
      labor induction (7.9% compared with 4.8%, P=.04) and cesarean delivery (12.1%
      compared with 5.1%, P<.001). They also had higher rates of placental abruption
      (0.9% compared with 0.2%, P=.02), abnormal or intermediate fetal heart rate (FHR)
      tracings (7.0% compared with 3.2%, P=.002), and prolonged first stage of delivery
      (6.0% compared with 1.4%, P<.001). Isolated polyhydramnios was also associated
      with higher rates of shoulder dystocia (1.9% compared with 0.3%, P<.001) and
      respiratory distress syndrome (0.5% compared with 0.03%, P=.001). On a multiple
      logistic regression model, isolated polyhydramnios was an independent risk factor
      for labor induction (adjusted odds ratio [OR] 1.7, 95% confidence interval [CI]
      1.01-2.8), cesarean delivery (adjusted OR 2.6, 95% CI 1.7-4.0), prolonged first
      stage of delivery (adjusted OR 3.6, 95% CI 1.97-6.7), abnormal or intermediate
      FHR tracings (adjusted OR 2.6, 95% CI 1.6-4.5), placental abruption (adjusted OR
      8.4, 95% CI 2.00-35.4), shoulder dystocia (adjusted OR 3.4, 95% CI 1.2-9.7), and
      respiratory distress syndrome (adjusted OR 38.9, 95% CI 4.6-332.6). Mild isolated
      polyhydramnios (AFI 25.1-30.0) was independently associated with cesarean
      delivery, prolonged first stage of delivery, placental abruption, abnormal or
      intermediate FHR tracings, and shoulder dystocia. CONCLUSION: Isolated
      polyhydramnios at admission for labor at or beyond 34 weeks of gestation is
      associated with adverse obstetric and neonatal outcomes.

PMID- 25751212
TI  - Red blood cell salvage during obstetric hemorrhage.
AB  - OBJECTIVE: To describe which obstetric patients lose enough blood during
      postpartum hemorrhage to receive a reinfusion of intraoperative blood salvage.
      METHODS: Eight years of intraoperative blood salvage data from a regional
      tertiary care maternity hospital were analyzed. The volume of blood returned
      through intraoperative blood salvage was standardized to the volume of red blood
      cells in an allogeneic red blood cell unit from the blood bank. RESULTS: There
      were 884 obstetric hemorrhage cases in which intraoperative blood salvage was
      utilized. Sufficient blood was collected by intraoperative blood salvage to
      permit reinfusion in 189 of 884 (21%) patients. For patients in whom
      intraoperative blood salvage blood was reinfused, the mean +/- standard deviation
      number of reinfused shed blood units was 1.2 +/- 1.1 units. Although
      intraoperative blood salvage was most commonly performed on patients who
      underwent routine cesarean delivery (748/884 patients), only 13% of these
      patients received an intraoperative blood salvage reinfusion; 73% of the patients
      undergoing cesarean hysterectomy, 69% of those who had bleeding after cesarean
      delivery, and 53% of the patients who bled after vaginal delivery received an
      intraoperative blood salvage reinfusion (P<.001). CONCLUSION: Although
      intraoperative blood salvage was attempted on many patients, on only 21% of the
      women was a sufficient amount of intraoperative shed blood collected to proceed
      with reinfusion. Patients who experienced bleeding or who underwent a cesarean
      hysterectomy were the most likely to receive a reinfusion of intraoperative blood
      salvage-processed blood.

PMID- 25751213
TI  - Uterus transplantation: the ethics of moving the womb.
AB  - Although currently in the early clinical research phase, the first successful
      birth of a child after uterus transplant is an early step toward another
      reproductive option for women with uterine factor infertility. Uterus
      transplantation uniquely brings together the fields of assisted reproductive
      technology and transplant medicine and represents the world's first ephemeral
      transplant completed to improve quality of life rather than extending life.
      However, the ethical, legal, and social implications of uterus transplantation
      must be carefully analyzed for the donor, recipient, and resulting child before
      uterus transplant moves from clinical research to clinical practice. 

PMID- 25751211
TI  - Reproductive health outcomes of insured adolescent and adult women who access
      oral levonorgestrel emergency contraception.
AB  - OBJECTIVE: To assess the level of risk for adolescents and women who seek
      emergency contraception through various clinical routes and the opportunities for
      improved care provision. METHODS: This study looked at a retrospective cohort to
      assess contraception and other reproductive health outcomes among adolescents and
      women aged 15-44 years who accessed oral levonorgestrel emergency contraception
      through an office visit or the call center at Kaiser Permanente Northern
      California from 2010 to 2011. RESULTS: Of 21,421 prescriptions, 14,531 (67.8%)
      were accessed through the call center. In the subsequent 12 months, 12,127
      (56.6%) adolescents and women had short-acting contraception (pills, patches,
      rings, depot medroxyprogesterone) dispensed and 2,264 (10.6%) initiated very
      effective contraception (intrauterine contraception, implants, sterilization).
      Initiation of very effective contraception was similar for adolescents and women
      who accessed it through the call center-1,569 (10.8%) and office visits-695
      (10.1%) (adjusted odds ratio [OR] 1.02, 95% confidence interval [CI] 0.93-1.13).
      In the subsequent 6 months, 2,056 (9.6%) adolescents and women became pregnant.
      Adolescents and women who accessed emergency contraception through the call
      center were less likely to become pregnant within 3 months of accessing emergency
      contraception than woman who accessed it through office visits (adjusted OR 0.82,
      95% CI 0.72-0.94); however, they were more likely to become pregnant within 4-6
      months (adjusted OR 1.37, 95% CI 1.16-1.60). Among adolescents and women who were
      tested for chlamydia and gonorrhea, 689 (7.8%) and 928 (7.9%) were positive in
      the 12 months before and after accessing emergency contraception, respectively.
      CONCLUSION: Protocols to routinely address unmet needs for contraception at every
      call for emergency contraception and all office visits, including visits with
      primary care providers, should be investigated.

PMID- 25751214
TI  - Pregnancy-related mortality in California: causes, characteristics, and
      improvement opportunities.
AB  - OBJECTIVE: To compare specific maternal and clinical characteristics and
      contributing factors among the five leading causes of pregnancy-related mortality
      to develop focused clinical and public health prevention programs. METHODS:
      California pregnancy-related deaths from 2002-2005 were identified with enhanced
      surveillance using linked birth and death certificates. A multidisciplinary
      committee reviewed medical records, autopsy reports, and coroner reports to
      determine cause of death, clinical and demographic characteristics, chance to
      alter outcome, contributing factors (at health care provider, facility, and
      patient levels), and quality improvement opportunities. The five leading causes
      of death were compared with each other and with the overall California birth
      population. RESULTS: Among the 207 pregnancy-related deaths, the five leading
      causes were cardiovascular disease, preeclampsia or eclampsia, hemorrhage, venous
      thromboembolism, and amniotic fluid embolism. Among the leading causes of death,
      we identified differing patterns for race, maternal age, body mass index, timing
      of death, and method of delivery. Overall, there was a good-to-strong chance to
      alter the outcome in 41% of deaths, with the highest rates of preventability
      among hemorrhage (70%) and preeclampsia (60%) deaths. Health care provider,
      facility, and patient contributing factors also varied by cause of death.
      CONCLUSION: Pregnancy-related mortality should not be considered a single
      clinical entity. Reducing mortality requires in-depth examination of individual
      causes of death. The five leading causes exhibit different characteristics,
      degrees of preventability, and contributing factors, with the greatest
      improvement opportunities identified for hemorrhage and preeclampsia. These
      findings provide additional support for hospital, state, and national maternal
      safety programs.

PMID- 25751215
TI  - Low-dose aspirin and preterm birth: a randomized controlled trial.
AB  - OBJECTIVE: To evaluate the association between low-dose aspirin initiated before
      conception and the risk of preterm birth. METHODS: This was a secondary analysis
      of the Effects of Aspirin in Gestation and Reproduction trial. Women with a
      history of pregnancy loss (original stratum: one loss less than 20 weeks of
      gestation during the previous year; expanded stratum: one or two losses with no
      restrictions on timing or gestational age of the losses) were randomized to
      either daily low-dose aspirin (81 mg, n=615) and folic acid or folic acid alone
      (placebo; n=613). Preterm birth was compared between groups using intent-to-treat
      analysis. RESULTS: Preterm birth rates were 4.1% (22/535 low-dose aspirin) and
      5.7% (31/543 placebo) (relative risk [RR] 0.72, 95% confidence interval [CI] 0.42
      1.23); spontaneous preterm birth rates were 1.1% (6/535 low-dose aspirin) and
      2.2% (12/543 placebo) (RR 0.51, 95% CI 0.19-1.34); medically indicated preterm
      birth rates were 2.6% (14/535 low-dose aspirin) and 2.9% (16/543 placebo) (RR
      0.89, 95% CI 0.44-1.80). After restriction to confirmed pregnancies using inverse
      probability weighting, preterm birth rates were 5.7% and 9.0% (RR 0.63, 95% CI
      0.37-1.09) and spontaneous preterm birth rates were 1.4% and 3.2% (RR 0.44, 95%
      CI 0.17-1.18). In confirmed pregnancies in the original stratum, preterm birth
      occurred in 3.8% and 9.7% of the low-dose aspirin and placebo groups,
      respectively (RR 0.39, 95% CI 0.16-0.94). CONCLUSION: Preconception low-dose
      aspirin was not significantly associated with the overall rate of preterm birth.
      Although the study was underpowered for this secondary analysis, numeric trends
      in favor of benefit, particularly in the women with a recent, single early
      pregnancy loss, warrant further investigation. CLINICAL TRIAL REGISTRATION:
      ClinicalTrials.gov, www.clinicaltrials.gov, NCT00467363.

PMID- 25751216
TI  - Prevalence and characteristics associated with gestational weight gain adequacy.
AB  - OBJECTIVE: To estimate the prevalence of gestational weight gain adequacy
      according to the 2009 Institute of Medicine recommendations and examine
      demographic, behavioral, psychosocial, and medical characteristics associated
      with inadequate and excessive gain stratified by prepregnancy body mass index
      (BMI) category. METHODS: We used cross-sectional, population-based data on women
      delivering full-term (37 weeks of gestation or greater), singleton neonates in 28
      states who participated in the 2010 or 2011 Pregnancy Risk Assessment Monitoring
      System. We estimated adjusted odds ratios (ORs) and 95% confidence intervals
      (CIs) for inadequate and excessive compared with adequate gain, stratified by
      prepregnancy BMI. RESULTS: Overall, 20.9%, 32.0%, and 47.2% of women gained
      inadequate, adequate, and excessive gestational weight, respectively.
      Prepregnancy BMI was strongly associated with weight gain outside
      recommendations. Compared with normal-weight women (prevalence 51.8%),
      underweight women (4.2%) had decreased odds of excessive gain (adjusted OR 0.50,
      CI 0.40-0.61), whereas overweight and obese class I, II, and III (23.6%, 11.7%,
      5.4%, and 3.5%, respectively) women had increased odds of excessive gain
      (adjusted OR range 2.07, CI 1.63-2.62 to adjusted OR 2.99, CI 2.63-3.40).
      Underweight and obese class II and III women had increased odds of inadequate
      gain (adjusted OR 1.25, CI 1.01-1.55 to 1.86, CI 1.45-2.36). Most characteristics
      associated with weight gain adequacy were demographic such as racial or ethnic
      minority status and education and varied by prepregnancy BMI. Notably, one
      behavioral characteristic-smoking cessation-was associated with excessive gain
      among normal-weight and obese women. CONCLUSION: Most women gained weight outside
      recommendations. Understanding characteristics associated with inadequate or
      excessive weight gain may identify potentially at-risk women and inform much
      needed interventions.

PMID- 25751217
TI  - Perinatal outcomes with normal compared with elevated umbilical artery systolic
      to-diastolic ratios in fetal growth restriction.
AB  - OBJECTIVE: To compare the composite neonatal morbidity of pregnancies with fetal
      growth restriction (estimated fetal weight less than the 10th percentile) and
      normal compared with elevated umbilical artery systolic-to-diastolic ratios.
      METHODS: This was a retrospective cohort study of all pregnancies complicated by
      fetal growth restriction with normal compared with elevated umbilical artery
      systolic-to-diastolic ratios from January 2008 to July 2012 at a single center.
      Exclusions were multiple gestation, prenatally diagnosed fetal anomalies,
      delivery at outside institution, and absent or reversed end diastolic flow.
      Maternal characteristics and perinatal outcomes including composite neonatal
      morbidity were compared between groups. RESULTS: Of 11,785 pregnancies evaluated,
      789 (7%) were diagnosed with fetal growth restriction. Among 512 that met
      inclusion criteria, 394 (77%) had normal and 118 (23%) had elevated umbilical
      artery systolic-to-diastolic ratios. When fetal growth-restricted pregnancies
      with elevated umbilical artery systolic-to-diastolic ratios were delivered at 37
      weeks of gestation were compared with those with normal umbilical artery systolic
      to-diastolic ratios delivered at 39 weeks of gestation, there was no difference
      in the rate of neonatal intensive care unit admission (101 [25.7%] compared with
      51 [43.2%]; crude odds ratio [OR] 2.5, 95% confidence interval 1.5-4.0; adjusted
      OR 1.37, 95% CI 0.69-2.71) or composite neonatal morbidity (60 [15.2%] compared
      with 24 [20.3%]; crude OR 1.42, 95% CI 0.84-2.40; adjusted OR 0.91, 95% CI 0.45
      1.84). CONCLUSION: Composite neonatal morbidity is comparable in fetal growth
      restricted pregnancies with elevated compared with normal umbilical artery
      systolic-to-diastolic ratios when delivered at 37 and 39 weeks of gestation,
      respectively. Planning delivery of pregnancies with fetal growth restriction and
      elevated systolic-to-diastolic ratios and without other complications at 37 weeks
      of gestation results in good outcomes.

PMID- 25751218
TI  - Validation of a vaginal birth after cesarean delivery prediction model in women
      with two prior cesarean deliveries.
AB  - OBJECTIVE: To evaluate whether an existing vaginal birth after cesarean delivery
      (VBAC) prediction model validated for women with one prior cesarean delivery also
      accurately predicts the likelihood of VBAC in women with two prior cesarean
      deliveries. METHODS: We performed a secondary analysis of all women attempting
      trial of labor after cesarean delivery (TOLAC) with a term singleton pregnancy
      and two prior cesarean deliveries in the Maternal-Fetal Medicine Units Network
      (MFMU) Cesarean Registry. Probability of VBAC was calculated for each participant
      using the MFMU VBAC prediction model. Women were considered to have a recurring
      indication for cesarean delivery if the indication for either their first or
      second cesarean delivery was arrest of dilation or descent. A receiver operating
      characteristic curve was used to assess the classification ability of the model
      and the predicted likelihood of VBAC success was compared with the actual
      likelihood using a calibration curve. RESULTS: Among 369 women with two prior
      cesarean deliveries undergoing TOLAC, the actual VBAC rate was 66% (95%
      confidence interval [CI] 61-71). The mean predicted probability of VBAC was
      higher among women with a successful TOLAC than those with a failed TOLAC (75%
      compared with 59%, P<.001). The area under the receiver operating characteristic
      curve for women with two prior cesarean deliveries was 0.74 (95% CI 0.69-0.80).
      Within deciles of predicted probability greater than 30%, predicted probabilities
      were similar to and contained actual probabilities within the 95% CI. CONCLUSION:
      The estimates of VBAC success based on the MFMU prediction model are similar to
      the actual rates observed among women with two prior cesarean deliveries.

PMID- 25751219
TI  - Preterm birth or small for gestational age in a singleton pregnancy and risk of
      recurrence in a subsequent twin pregnancy.
AB  - OBJECTIVE: To evaluate whether a history of preterm birth or small for
      gestational age (SGA) in a singleton pregnancy is associated with an increased
      risk of recurrence of the same condition in a subsequent twin pregnancy. METHODS:
      Retrospective cohort study of twin pregnancies delivered in one maternal-fetal
      medicine practice from 2005 to 2014. Patients with a history of singleton preterm
      birth at less than 37 weeks of gestation were compared with patients with a
      history of singleton term birth and nulliparous patients. A similar analysis was
      performed for a history of SGA (birth weight less than 10%). RESULTS: Six hundred
      forty-seven twin pregnancies were included. The prior singleton gestational age
      at delivery was significantly positively correlated with the twin gestational age
      at delivery (P<.001), and the prior singleton birth weight was significantly
      positively correlated with the birth weight of the larger twin (P<.001) and the
      smaller twin (P<.001). The rate of twin preterm birth before 32 weeks of
      gestation was 3.5% in patients with a prior term birth, 9.2% in nulliparous
      patients, and 26% in patients with a prior preterm birth (P<.001). The rate of
      SGA in patients with a prior birth not complicated by SGA was 42.1%, in
      nulliparous women it was 54.4%, and in patients with a history of SGA it was
      65.2% (P=.007). On regression analysis, prior preterm birth and SGA of a
      singleton pregnancy were independently associated with recurrence of the same
      condition in a subsequent twin pregnancy. CONCLUSION: Prior preterm birth and SGA
      in a singleton pregnancy increase the risk of the same condition in a subsequent
      twin pregnancy. We postulate that the extrinsic mechanism responsible for the
      pathophysiology of adverse outcomes in twin pregnancies overlaps with that in
      singleton pregnancies.

PMID- 25751220
TI  - The sky is not falling, but it is severely drooping for the specialist
      obstetrician-gynecologist.

PMID- 25751221
TI  - Ablative fractional laser resurfacing for abdominal scar contractures in
      pregnancy.
AB  - BACKGROUND: Fundal growth during pregnancy can lead to unremitting discomfort and
      skin breakdown in patients with extensive abdominal scarring. CASE: A 31-year-old
      primigravid woman at 30 weeks of gestation presented to the department of
      dermatology with constant abdominal discomfort, itch, and sleep disturbance
      secondary to increasing tension associated with existing abdominal scars. An
      outpatient course of ablative fractional laser resurfacing was initiated in
      consultation with the dermatology department, resulting in immediate and durable
      symptom relief and visible abdominal expansion. No complications were observed,
      and the patient delivered a healthy newborn at term. CONCLUSIONS: Ablative
      fractional laser resurfacing is a minimally invasive therapeutic alternative for
      treating pregnant patients with symptoms related to restrictive scarring of the
      abdomen.

PMID- 25751222
TI  - Emergency preparedness in obstetrics.
AB  - During and after disasters, focus is directed toward meeting the immediate needs
      of the general population. As a result, the routine health care and the special
      needs of some vulnerable populations such as pregnant and postpartum women may be
      overlooked within a resource-limited setting. In the event of hazards such as
      natural disasters, manmade disasters, and terrorism, knowledge of emergency
      preparedness strategies is imperative for the pregnant woman and her family,
      obstetric providers, and hospitals. Individualized plans for the pregnant woman
      and her family should include knowledge of shelter in place, birth at home, and
      evacuation. Obstetric providers need to have a personal disaster plan in place
      that accounts for work responsibilities in case of an emergency and business
      continuity strategies to continue to provide care to their communities. Hospitals
      should have a comprehensive emergency preparedness program utilizing an "all
      hazards" approach to meet the needs of pregnant and postpartum women and other
      vulnerable populations during disasters. With lessons learned in recent tragedies
      such as Hurricane Katrina in mind, we hope this review will stimulate emergency
      preparedness discussions and actions among obstetric providers and attenuate
      adverse outcomes related to catastrophes in the future. 

PMID- 25751223
TI  - Stillbirth and fetal death: time for standard definitions and improved reporting.

PMID- 25751224
TI  - What is new in the use of mesh in vaginal surgery? Best articles from the past
      year.
AB  - This month we focus on current research in use of mesh in vaginal surgery. Dr.
      Fischer discusses four recent publications, and each is concluded with a "bottom
      line" that is the take-home message. The complete reference for each can be found
      in Box 1 on this page, along with direct links to the abstracts. 

PMID- 25751225
TI  - Pregnancy and weight gain: we have observed enough.

PMID- 25751226
TI  - Addressing firearm-related violence in the United States.

PMID- 25751227
TI  - Multiparametric MR Imaging with High-Resolution Dynamic Contrast-enhanced and
      Diffusion-weighted Imaging at 7 T Improves the Assessment of Breast Tumors: A
      Feasibility Study.
AB  - PURPOSE: To ascertain whether multiparametric magnetic resonance (MR) imaging of
      the breast in combination with dynamic contrast material-enhanced (DCE) imaging
      and diffusion-weighted imaging (DWI) at 7 T is feasible and improves diagnostic
      accuracy. MATERIALS AND METHODS: From December 2011 to December 2013, 40 patients
      with suspicious breast lesions were included in this institutional review board
      approved prospective study. Before bilateral multiparametric MR imaging of the
      breast at 7 T, all patients gave written informed consent. Lesions were
      classified according to Breast Imaging Reporting and Data System (BI-RADS) and
      assessed for apparent diffusion coefficient (ADC) values by two readers
      independently. For combined analysis of DCE MR imaging and DWI, the BI-RADS
      adapted reading algorithm, which adapted ADC thresholds to the BI-RADS assessment
      category, was used. Diagnostic values of multiparametric, DCE MR imaging, and DWI
      were calculated. Receiver operating characteristic curve analysis was performed.
      Image quality and interreader agreement were assessed. Histopathologic results
      were used as the highest standard. RESULTS: There were 29 malignant and 17 benign
      lesions (range, 6-95 mm; mean, 23.3 mm). Multiparametric MR imaging yielded a
      sensitivity of 100% (29 of 29 lesions), a specificity of 88.2% (16 of 18
      lesions), and an area under the curve of 0.941, which was greater than for DCE MR
      imaging (P = .003), which had a sensitivity of 100% (29 of 29 lesions), a
      specificity of 53.2% (nine of 17 lesions), and an area under the curve of 0.765.
      DWI had a sensitivity of 93.1% (27 of 29 lesions), a specificity of 88.2% (15 of
      17 lesions), and an area under the curve of 0.907. Multiparametric MR imaging at
      7 T of the breast eliminated all false-negative findings and reduced false
      positive findings, from eight false-positive findings with DCE MR imaging to two
      false-positive findings. Thus, if used clinically, 7-T multiparametric MR imaging
      may have potentially obviated unnecessary breast biopsies in six of eight lesions
      (P = .031). Multiparametric MR imaging demonstrated either excellent or good
      image quality and interreader agreement (kappa = 0.89-1.00). CONCLUSION: The
      clinical use of 7-T multiparametric MR imaging is feasible, provides good or
      excellent image quality, and has the potential to improve diagnostic accuracy.

PMID- 25751228
TI  - Diagnostic Performance of an Advanced Modeled Iterative Reconstruction Algorithm
      for Low-Contrast Detectability with a Third-Generation Dual-Source Multidetector
      CT Scanner: Potential for Radiation Dose Reduction in a Multireader Study.
AB  - PURPOSE: To assess the effect of radiation dose reduction on low-contrast
      detectability by using an advanced modeled iterative reconstruction (ADMIRE;
      Siemens Healthcare, Forchheim, Germany) algorithm in a contrast-detail phantom
      with a third-generation dual-source multidetector computed tomography (CT)
      scanner. MATERIALS AND METHODS: A proprietary phantom with a range of low
      contrast cylindrical objects, representing five contrast levels (range, 5-20 HU)
      and three sizes (range, 2-6 mm) was fabricated with a three-dimensional printer
      and imaged with a third-generation dual-source CT scanner at various radiation
      dose index levels (range, 0.74-5.8 mGy). Image data sets were reconstructed by
      using different section thicknesses (range, 0.6-5.0 mm) and reconstruction
      algorithms (filtered back projection [FBP] and ADMIRE with a strength range of
      three to five). Eleven independent readers blinded to technique and
      reconstruction method assessed all data sets in two reading sessions by measuring
      detection accuracy with a two-alternative forced choice approach (first session)
      and by scoring the total number of visible object groups (second session). Dose
      reduction potentials based on both reading sessions were estimated. Results
      between FBP and ADMIRE were compared by using both paired t tests and analysis of
      variance tests at the 95% significance level. RESULTS: During the first session,
      detection accuracy increased with increasing contrast, size, and dose index
      (diagnostic accuracy range, 50%-87%; interobserver variability, +/-7%). When
      compared with FBP, ADMIRE improved detection accuracy by 5.2% on average across
      the investigated variables (P < .001). During the second session, a significantly
      increased number of visible objects was noted with increasing radiation dose
      index, section thickness, and ADMIRE strength over FBP (up to 80% more visible
      objects, P < .001). Radiation dose reduction potential ranged from 56% to 60% and
      from 4% to 80% during the two sessions, respectively. CONCLUSION: Low-contrast
      detectability performance increased with increasing object size, object contrast,
      dose index, section thickness, and ADMIRE strength. Compared with FBP, ADMIRE
      allows a substantial radiation dose reduction while preserving low-contrast
      detectability. Online supplemental material is available for this article.

PMID- 25751229
TI  - Single Hepatocellular Carcinoma: Preoperative MR Imaging to Predict Early
      Recurrence after Curative Resection.
AB  - PURPOSE: To identify magnetic resonance (MR) imaging features that enable
      prediction of early recurrence (<2 years) after curative resection of
      hepatocellular carcinoma (HCC) and to derive a preoperative prediction model.
      MATERIALS AND METHODS: This retrospective study was approved by the institutional
      review board. The requirement to obtain written informed consent was waived. A
      total of 268 patients who underwent hepatic resection for a single HCC from
      January 2008 to August 2011 were divided into two cohorts: a training cohort,
      which was used to derive a prediction model (n = 187), and a validation cohort (n
      = 81). All MR images from the training cohort were reviewed by two radiologists.
      A prediction model was constructed by using MR imaging features that were
      independently associated with early recurrence with use of multiple logistic
      regression analysis. The performance of the prediction model in the validation
      cohort was evaluated with respect to discrimination (ie, whether the relative
      ranking of individual predictions of subsequent early recurrence is in the
      correct order). RESULTS: In the training cohort, four MR imaging features were
      independently associated with early recurrence: rim enhancement (odds ratio [OR]
      = 3.83; 95% confidence interval [CI]: 1.39, 10.52), peritumoral parenchymal
      enhancement in the arterial phase (OR = 2.64; 95% CI: 1.27, 5.46), satellite
      nodule (OR = 4.07; 95% CI: 1.09, 15.21), and tumor size (OR = 1.66; 95% CI: 1.31,
      2.09). A prediction model derived from these variables showed an area under the
      receiver operating characteristic curve (AUC) of 0.788 in the prediction of the
      risk of early recurrence in the training cohort. When applied to the validation
      cohort, this model showed good discrimination (AUC, 0.783). CONCLUSION: The
      prediction model derived from rim enhancement, peritumoral parenchymal
      enhancement, satellite nodule, and tumor size can be used preoperatively to
      estimate the risk of early recurrence after resection of a single HCC.

PMID- 25751230
TI  - The Association Between Food Insufficiency and HIV Treatment Outcomes in a
      Longitudinal Analysis of HIV-Infected Individuals in New York City.
AB  - BACKGROUND: To date, there have been few longitudinal studies of food insecurity
      among people living with HIV (PLWH). Food insufficiency (FI) is one dimension of
      the food insecurity construct that refers to periods of time during which
      individuals have an inadequate amount of food intake because of limited
      resources. The aim of this analysis was to examine the relationship between FI
      and HIV treatment outcomes among HIV-infected individuals in New York City (NYC).
      METHODS: Associations between FI ("consistent"--food insufficient on both of the
      last 2 assessments, "inconsistent"--food insufficient on 1 of the last 2
      assessments, or neither) and clinical indicators of HIV disease progression
      (viral load > 200 copies per milliliter, CD4 count < 200 cells per cubic
      millimeter) were analyzed for NYC Ryan White Part A food and nutrition program
      clients who were matched to the NYC HIV Surveillance Registry and completed 2 FI
      assessments between November 2011 and June 2013. RESULTS: Among 2,118 PLWH in
      food and nutrition programs, 61% experienced consistent FI and 25% experienced
      inconsistent FI. In multivariate analyses controlling for sociodemographic
      characteristics, consistent FI was independently associated with unsuppressed
      viral load (adjusted odds ratio = 1.6, confidence interval: 1.1 to 2.5).
      Consistent FI was only associated with low CD4 counts at the bivariate level.
      CONCLUSIONS: Future studies should examine biological, structural, and
      psychosocial factors that may explain the relationship between FI and HIV
      treatment outcomes to inform intervention development. Persistent FI among food
      and nutrition program clients suggests that services are needed to address
      underlying needs for financial stability (eg, vocational counseling) for PLWH.

PMID- 25751231
TI  - N463 Glycosylation Site on V5 Loop of a Mutant gp120 Regulates the Sensitivity of
      HIV-1 to Neutralizing Monoclonal Antibodies VRC01/03.
AB  - BACKGROUND: HIV-1 gp120/gp41 is heavily modified by n-linked carbohydrates that
      play important roles either in correct folding or in shielding vulnerable viral
      protein surfaces from antibody recognition. METHODS: In our previous work, 25
      potential N-linked glycosylation sites (PNGS) of a CRF07_BC isolate of HIV-1 were
      individually mutated, and the resulting effects on infectivity and antibody
      mediated neutralization were evaluated. To further understand the functional role
      of these PNGS, we generated double and multiple mutants from selected individual
      PNGS mutants. The effects were then evaluated by examining infectivity and
      sensitivity to antibody-mediated neutralization by neutralizing monoclonal
      antibodies (nMAbs) and serum antibodies from HIV-1 positive donors. RESULTS:
      Infectivity results showed that, among the 12 combined PNGS mutants, only 197M.1
      (N197D/N301Q) lost infectivity completely, whereas all others (except for 197M.6)
      showed reduced viral infectivity. In terms of neutralization sensitivity to known
      nMAbs, we found that adding N463Q mutation to all the gp120 mutants containing
      N197D significantly increased neutralization sensitivity to VRC01 and VRC03,
      suggesting N197 and N463 have a strong synergistic effect in regulating the
      neutralizing sensitivity of HIV-1 to the anti-CD4bs nMAbs VRC01/VRC03. Structural
      analysis based on the available structures of gp120 alone and in complex with CD4
      and various nMAbs elucidates a molecular rationale for this experimental
      observation. CONCLUSIONS: The data indicate that N463 plays an important role in
      regulating the CD4bs MAbs VRC01/VRC03 sensitivity in the genetic background of
      N197D mutation of gp120, which should provide valuable information for a better
      understanding of the interplay between HIV-1 and VRC01/03.

PMID- 25751232
TI  - Effect of Therapeutic Hypercapnia on Inflammatory Responses to One-lung
      Ventilation in Lobectomy Patients.
AB  - BACKGROUND: One-lung ventilation (OLV) can result in local and systemic
      inflammation. This prospective, randomized trial was to evaluate the effect of
      therapeutic hypercapnia on lung injury after OLV. METHOD: Fifty patients aged 20
      to 60 yr undergoing lobectomy were randomly provided with air or carbon dioxide
      (partial pressure of carbon dioxide: 35 to 45 mmHg or 60 to 70 mmHg). Peak
      pressure, plateau pressure, and lung compliance were recorded. Bronchoalveolar
      lavage fluid (BALF) and blood samples were collected. Adverse events were
      monitored. The primary outcome was the concentration of BALF tumor necrosis
      factor, and the secondary outcomes were serum cytokine concentrations. RESULTS:
      The BALF tumor necrosis factor was lower in the carbon dioxide group than in the
      air group (median [range], 51.1 [42.8 to 76.6] vs. 71.2 [44.8 to 92.7]; P =
      0.034). Patients in the carbon dioxide group had lower concentrations of serum
      and BALF interleukin (IL)-1, IL-6, and IL-8, but higher serum concentrations of
      IL-10, accompanied by reduced numbers of cells and neutrophils as well as lower
      concentrations of protein in the BALF. Also, patients in the carbon dioxide group
      had lower peak (mean +/- SD, 22.2 +/- 2.9 vs. 29.8 +/- 4.6) and plateau pressures
      (20.5 +/- 2.4 vs. 27.1 +/- 2.9), but higher dynamic compliance (46.6 +/- 5.8 vs.
      38.9 +/- 6.5). Furthermore, patients in the carbon dioxide group had higher
      postoperation oxygenation index values. Ten patients experienced slightly
      increased blood pressure and heart rate during OLV in the carbon dioxide group.
      CONCLUSION: Under intravenous anesthesia, therapeutic hypercapnia inhibits local
      and systematic inflammation and improves respiratory function after OLV in
      lobectomy patients without severe complications.

PMID- 25751233
TI  - Noble path to oblivion: molecular and neurophysiological mechanisms of xenon.

PMID- 25751234
TI  - Opioid-induced Respiratory Depression Is Only Partially Mediated by the
      preBotzinger Complex in Young and Adult Rabbits In Vivo.
AB  - BACKGROUND: The preBotzinger Complex (preBC) plays an important role in
      respiratory rhythm generation. This study was designed to determine whether the
      preBC mediated opioid-induced respiratory rate depression at clinically relevant
      opioid concentrations in vivo and whether this role was age dependent. METHODS:
      Studies were performed in 22 young and 32 adult New Zealand White rabbits.
      Animals were anesthetized, mechanically ventilated, and decerebrated. The preBC
      was identified by the tachypneic response to injection of D,L-homocysteic acid.
      (1) The MU-opioid receptor agonist [D-Ala2,N-Me-Phe4,Gly-ol]-enkephalin (DAMGO,
      100 MUM) was microinjected into the bilateral preBC and reversed with naloxone (1
      mM) injection into the preBC. (2) Respiratory depression was achieved with
      intravenous remifentanil (0.08 to 0.5 MUg kg(-1) min(-1)). Naloxone (1 mM) was
      microinjected into the preBC in an attempt to reverse the respiratory depression.
      RESULTS: (1) DAMGO injection depressed respiratory rate by 6 +/- 8 breaths/min in
      young and adult rabbits (mean +/- SD, P < 0.001). DAMGO shortened the inspiratory
      and lengthened the expiratory fraction of the respiratory cycle by 0.24 +/- 0.2
      in adult and young animals (P < 0.001). (2) During intravenous remifentanil
      infusion, local injection of naloxone into the preBC partially reversed the
      decrease in inspiratory fraction/increase in expiratory fraction in young and
      adult animals (0.14 +/- 0.14, P < 0.001), but not the depression of respiratory
      rate (P = 0.19). PreBC injections did not affect respiratory drive. In adult
      rabbits, the contribution of non-preBC inputs to expiratory phase duration was
      larger than preBC inputs (3.5 [-5.2 to 1.1], median [25 to 75%], P = 0.04).
      CONCLUSIONS: Systemic opioid effects on respiratory phase timing can be partially
      reversed in the preBC without reversing the depression of respiratory rate.

PMID- 25751235
TI  - Personalized pain medicine: pipe dream or reality?

PMID- 25751236
TI  - Hypoxia induced gene expression: the specificity switch!

PMID- 25751237
TI  - A longitudinal study of streptococcus pneumoniae carriage in healthy children in
      the 13-valent pneumococcal conjugate vaccine era.
AB  - Few epidemiological data are available after the introduction of the 13-valent
      pneumococcal vaccine (PCV13) in 2010. We performed repeat nasopharyngeal swabs
      and evaluated the serotype distribution of Streptococcus pneumoniae (SP) and its
      association with PCV13 vaccine status in healthy Italian children aged 3-59
      months. SP serotypes were assessed by the Quellung reaction. 618 children
      appropriately (28%) or incompletely (72%) vaccinated for age with PCV13 were
      available at baseline (T0). 515 were re-evaluated at 6 months from baseline (T6)
      and 436 at 12 months from baseline (T12). The percentage of appropriately
      vaccinated subjects at T0, T6 and T12 was 28%, 67% and 92%, respectively. Random
      effects logistic regression models with robust 95% confidence intervals was used
      to estimate the time-related changes in SP and PCV13 carriage and marginal
      probabilities were obtained from such models. The age-corrected probability of SP
      carriage was 0.31 (95% CI 0.22 - 0.41) at T0, 0.32 (0.24 - 0.40) at T6 and 0.28
      (0.20 - 0.35) at T12. The probability of PCV13 serotypes carriage was 0.025
      (0.001 - 0.050) at T0, 0.018 (0.001 - 0.039) at T6 and 0.010 (0.001 - 0.023) at
      T12. A decrease in PCV13 serotypes and a shift in non-PCV13 serotypes
      colonization was observed. In particular, the 15A serotype accounted for 4%, 8%
      and 23% of SP isolates at T0, T6 and T12, respectively. In conclusion, the
      benefits of the PCV13 vaccination on SP carriage increase with increasing
      coverage rates. The shift of SP isolates toward non-PCV13 serotypes needs to be
      studied further. 

PMID- 25751239
TI  - Indirect internal carotid-cavernous fistula in infancy.
AB  - A 4-month-old male infant with proptosis and episcleral injection initially
      thought to have orbital inflammation was found to have an indirect carotid
      cavernous sinus fistula. He was treated conservatively without worsening of
      symptoms. The authors report the first case of indirect carotid-cavernous sinus
      fistula in an infant originating from the internal carotid artery.

PMID- 25751238
TI  - Changes in PTSD and Depression During Prolonged Exposure and Client-Centered
      Therapy for PTSD in Adolescents.
AB  - Depressive symptoms are common among individuals with posttraumatic stress
      disorder (PTSD). Prolonged exposure therapy (PE) for PTSD has been found to
      alleviate both PTSD and depressive symptoms, but relatively little is known about
      the pattern of PTSD and depressive symptom change during treatment. This study
      aimed to investigate the relationship between changes in PTSD and depression
      during PE for adolescent (PE-A) and client-centered therapy (CCT). The moderating
      role of PE-A versus CCT and the possible differences across symptom clusters of
      PTSD were also examined. Participants were 61 female adolescents with sexual
      assault-related PTSD randomized to PE-A (n = 31) or CCT (n = 30). Participants
      completed the Beck Depression Inventory and the Child PTSD Symptom Scale at pre-,
      mid-, and posttreatment and before each treatment session. Multilevel mediation
      analysis indicated a reciprocal but asymmetrical relationship between changes in
      PTSD and depression during treatment in the overall sample. Moderated mediation
      analysis showed that the reciprocal relation was observed only during PE-A.
      Reductions in PTSD led to reductions in depression to a greater extent (48.7%),
      95% confidence interval [30.2, 67.2], than vice versa (22.0%), [10.6, 33.4]. For
      participants receiving CCT, reduction in PTSD led to reductions in depression
      (31.6%), [11.8, 51.4], but not vice versa (7.4%), [-7.1, 21.9]. The reciprocal
      relationship between PTSD and depression was also observed across different
      symptoms clusters of PTSD. Our findings suggest that changes in PTSD led to
      changes in depressive symptoms to a greater extent than vice versa across PE-A
      and CCT.

PMID- 25751240
TI  - Comparison of time-and-motion observations and self-reports to capture mobility
      related nursing care activities for hospitalized older adults.
AB  - Mobility-related nursing care activities are provided infrequently for older
      adults in inpatient practice. Accurate quantification of these activities is
      critical to understanding patterns of delivery of nursing care and developing or
      redesigning work processes to improve patients' outcomes. The current exploratory
      study compares two continuous data-collecting methods: (a) self-reporting and (b)
      time-and-motion (TAM) observation of mobility-related nursing care activities for
      hospitalized older adults. A total of 84 patient-level data were captured by
      observing 43 8-hour shifts of 14 RNs by trained research observers. RNs
      continuously documented all types of nursing care activities that occurred during
      observation shifts. The frequency and duration of mobility activities between
      data obtained from RNs' self-reports and the TAM observations had poor agreement.
      Compared to the data from the TAM observations, RNs underreported the frequency
      of their mobility-related nursing care activities and overreported the duration.
      The authors' data suggest that a continuous TAM observation method is recommended
      to obtain accurate data on nurses' provision of mobility-related care activities
      to older adults.

PMID- 25751241
TI  - Dose - response relationship of bevacizumab in hereditary hemorrhagic
      telangiectasia.
AB  - Hereditary hemorrhagic telangiectasia (HHT), a genetic vascular disorder
      associated with epistaxis and hepatic shunts, is responsible for high-output
      cardiac failure in rare cases. Bevacizumab, which targets vascular endothelial
      growth factor, was shown to decrease both cardiac index (CI) and epistaxis
      duration in HHT patients with severe liver involvement. The relationship between
      its serum concentration and change in both CI and epistaxis duration was
      investigated to design the bevacizumab maintenance dosing regimen of future
      therapeutic studies. Twenty-five HHT patients with dyspnea and high CI were
      included in a prospective non-comparative study. They received bevacizumab at a
      dose of 5 mg/kg per infusion every 14 days for a total of 6 injections. The
      relationships between bevacizumab serum concentration and both CI and epistaxis
      duration were described using transit compartments and direct inhibition
      pharmacokinetic-pharmacodynamic models. The performances of different maintenance
      regimens were evaluated using simulation. Infusions every 3, 2 and one months
      were predicted to maintain 41%, 45% and 50% of patients with CI <4 L/min/m(2) at
      24 months, respectively. The fraction of patients with <20 min epistaxis per
      month was predicted to be 34%, 43% and 60%, with infusion every 3, 2 or one
      months, respectively. Simulations of the effects of different maintenance dosing
      regimens predict that monthly 5 mg/kg infusions of bevacizumab should allow
      sustained control of both cardiac index and epistaxis.

PMID- 25751242
TI  - Genetic Modifiers in beta-Thalassemia Intermedia: A Study on 102 Iraqi Arab
      Patients.
AB  - To determine the molecular basis of beta-thalassemia intermedia (TI) and the
      contribution of the three hemoglobin F (HbF) quantitative trait loci (QTLs) on
      chromosomes 11, 2, and 6 to the milder phenotype, a total of 102 Iraqi Arab
      patients with TI were studied. The beta and alpha genotypes as well as HBG2 g.
      158 C>T (rs7482144), BCL11A (rs1427407 and rs10189857), and HBS1L-MYB (rs28384513
      and rs9399137) by multiplex polymerase chain reaction and reverse hybridization
      were studied. A total of 21 different beta-thalassemia mutations arranged in 35
      different genotypes were identified. The genotypes encompassed beta(+)/beta(+)
      mutations in 33 cases, beta(+)/beta(0) in 17 cases, beta(0)/beta(0) in 47 cases,
      beta(0)/wild type in 3 and beta(0)/Hb E in 2 cases. The most common was IVS-II-1
      (G>A)/IVS-II-1 (G>A), followed by IVS-I-6 (T>C)/IVS-I-6 (T>C) and IVS-I-110
      (G>A)/IVS-I-110 (G>A), in 31.4%, 17.6%, and 6.9%, respectively. Alpha-thalassemia
      mutations were found in 15.2% of those homozygous for the beta-mutations, while
      alpha gene triplication was identified in all three heterozygotes. Of the five
      QTLs tested, only rs7482144 and rs10189857 were significantly associated with
      beta(0)/beta(0) when compared to beta(+)/beta(+), with odds ratios of 6.4 (95%
      confidence interval [CI] 2.9-14.0) and 3.2 (95% CI 1.2-8.6), respectively. In
      conclusion, this study has demonstrated that among Iraqi patients with thal
      intermedia, the main contributors to the milder phenotype were beta(+) alleles,
      XmnI polymorphism, and BCL11A (rs10189857), while other QTLs on chromosomes 2 and
      6, as well as alpha-thalassemia, were not significantly relevant. 

PMID- 25751243
TI  - A Si-MnOOH composite with superior lithium storage properties.
AB  - The Si-MnOOH composite electrode exhibits very stable cycling and excellent rate
      capability, such as 1200 mA h g(-1) at 12 A g(-1), and 700 mA h g(-1) at 20 A g(
      1). The gamma-MnOOH component significantly promotes the alloying/de-alloying
      reaction between Si and lithium. 

PMID- 25751244
TI  - The Medical Motorway: improving the quality of care in the context of an ageing
      population.
AB  - PURPOSE: The purpose of this article is to improve quality in health care.
      DESIGN/METHODOLOGY/APPROACH: This article developed the concepts of the health
      care services in the form of a Medical Motorway. FINDINGS: Different conceptual
      approaches to providing efficiency of services whilst improving quality of
      patient care in the context of an ageing population are presented.
      ORIGINALITY/VALUE: Personal viewpoint.

PMID- 25751245
TI  - A systemic approach to quality improvement in public health services.
AB  - Purpose - The purpose of this paper is to discuss the results of the first four
      years of implementation of a quality program called "Quality Contest" (QC). This
      program was implemented from 2007 onward to improve the quality of hospital
      services by the Moroccan Ministry of Health. The peculiarity of this
      intervention, held every 18 months, is that it combines several approaches (self
      evaluation, external audits with feedback, hospital ranking, awards and
      performance disclosure) and focuses on the quality of management.
      Design/methodology/approach - The assessment tool used to evaluate the quality of
      hospital management consists of 80 items. In each contest, a score is attributed
      to each item based on the score given for self-evaluation and the score given by
      external auditors. The sum of these scores allows the global performance score of
      the hospital to be obtained. To compare the performances over time and among
      hospitals, Wilcoxon signed-rank, Wilcoxon-Mann-Whitney and Kruskal-Wallis
      statistical tests were used. Findings - The results of the QC organized between
      2007 and 2010 revealed that the hospitals participating in all the three contests
      had significantly improved their performance levels in terms of the quality of
      management. There was also a significant association between the number of times
      hospitals participated in the QC and the performance scores attained.
      Originality/value - The paper reports an original quality improvement approach in
      a developing country that succeeded in triggering sustainable improvement
      dynamics by combining support (feedback) with reward (prizes) and pressure
      measures (ranking, performance disclosure). 

PMID- 25751246
TI  - Implementing a nationwide quality improvement approach in health services.
AB  - PURPOSE: The purpose of this paper is to present an innovative quality
      improvement intervention developed in Morocco and discuss its implementation.
      Until 2004, the Moroccan Ministry of Health (MoH) encouraged pilots of quality
      improvement approaches but none of them were revealed to be sustainable. Internal
      assessments pinpointed factors such as lack of recognition of the participating
      team's efforts and lack of pressure on managers to become more accountable. In
      2005, Morocco opted for an intervention called "Quality Contest" (QC) targeting
      health centres, hospitals and health district offices and combining quality
      measurement with structures ranking, performance disclosure and reward system.
      DESIGN/METHODOLOGY/APPROACH: The QC is organized every 18 months. After the self
      assessment and external audit step, the participating structures are ranked
      according to their scores. Their performances are then disseminated and the
      highest performing structures are rewarded. FINDINGS: The results showed an
      improvement in performance among participating structures, constructive exchange
      of successful experiences between structures, as well as communication of
      constraints, needs and expectations between MoH managers at central and local
      levels; the use of peer-auditors was appreciated as it enabled an exchange of
      best practices between auditors and audited teams but this was mitigated by the
      difficulty of ensuring their neutrality; and the recognition of efforts was
      appreciated but seemed insufficient to ensure a sense of justice and maintain
      motivation. ORIGINALITY/VALUE: This intervention is an example of MoH leadership
      that has succeeded in introducing transparency and accountability mechanisms
      (ranking and performance disclosure) as leverage to change the management culture
      of the public health services; setting up a reward system to reinforce motivation
      and adapting continuously the intervention to enhance its sustainability and
      acceptability.

PMID- 25751247
TI  - Developing a Physician Management & Leadership Program (PMLP) in Newfoundland and
      Labrador.
AB  - PURPOSE: This article aims to document the process the province of Newfoundland
      and Labrador used to develop an innovative Physician Management and Leadership
      Program (PMLP). The PMLP is a collaborative initiative among Memorial University
      (Faculty of Medicine and Faculty of Business), the Government of Newfoundland and
      Labrador, and the Regional Health Authorities. As challenges facing health-care
      systems become more complex there is a growing need for management and leadership
      training for physicians. DESIGN/METHODOLOGY/APPROACH: Memorial University Faculty
      of Medicine and the Gardiner Centre in the Faculty of Business in partnership
      with Regional Health Authorities and the Government of Newfoundland and Labrador
      identified the need for a leadership and management education program for
      physician leaders. A provincial needs assessment of physician leaders was
      conducted to identify educational needs to fill this identified gap. A Steering
      Committee was formed to guide the design and implementation and monitor delivery
      of the 10 module Physician Management and Leadership Program (PMLP). FINDINGS:
      Designing management and leadership education programs to serve physicians who
      practice in a large, predominately rural geographic area can be challenging and
      requires efficient use of available resources and technology. ORIGINALITY/VALUE:
      While there are many physician management and leadership programs available in
      Canada and abroad, the PMLP was designed to meet the specific educational needs
      of physician leaders in Newfoundland and Labrador.

PMID- 25751248
TI  - Country perspective on medical tourism: the Malaysian experience.
AB  - PURPOSE: The study seeks to explore the perception of international patients on
      Malaysia as a medical tourism destination country, as well as overall patient
      satisfaction, perceived value and future intention for repeat treatment and
      services. DESIGN/METHODOLOGY/APPROACH: Self-administered questionnaire was the
      main method of data collection. The survey covered major private hospitals in
      medical tourists' states in the country, namely, Penang, Melaka, Selangor and
      Kuala Lumpur. Convenience sampling was used due to the condition of patients as
      respondents. FINDINGS: Indonesian patients formed the largest majority of
      international patients in the country. Five dimensions of medical tourism in
      Malaysia was identified, namely, hospital and staff, country factor, combining
      tourism and health services, cost saving and insurance and unavailability of
      treatment. Of these, hospital and staff was found to be the most important factor
      for the patients. Perception of value, overall satisfaction and intention for
      future treatment was also found to be high. This indicates that Malaysia is on
      the right footing in this burgeoning industry. PRACTICAL IMPLICATIONS: Findings
      from the study will enable policy-makers to better position Malaysia as a medical
      tourist destination country. ORIGINALITY/VALUE: Medical tourism is a recent
      phenomenon and very little empirical research has been carried out at the patient
      level. This study is one of the first few studies which seek to explore medical
      tourism from the perspective of the patients themselves.

PMID- 25751249
TI  - Utilizing lean tools to improve value and reduce outpatient wait times in an
      Indian hospital.
AB  - PURPOSE: This paper aims to demonstrate how lean tools were applied to some
      unique issues of providing healthcare in a developing country where many patients
      face challenges not found in developed countries. The challenges provide insight
      into how lean tools can be utilized to provide similar results across the world.
      DESIGN/METHODOLOGY/APPROACH: This paper is based on a qualitative case study
      carried out by a master's student implementing lean at a hospital in India.
      FINDINGS: This paper finds that lean tools such as value-stream mapping and root
      cause analysis can lead to dramatic reductions in waste and improvements in
      productivity. The problems of the majority of patients paying for their own
      healthcare and lacking transportation created scheduling problems that required
      patients to receive their diagnosis and pay for treatment within a single day.
      Many additional wastes were identified that were significantly impacting the
      hospital's ability to provide care. As a result of this project, average
      outpatient wait times were reduced from 1 hour to 15 minutes along with a
      significant increase in labor productivity. PRACTICAL IMPLICATIONS: The results
      demonstrate how lean tools can increase value to the patients. It also provides
      are framework that can be utilized for healthcare providers in developed and
      developing countries to analyze their value streams to reduce waste.
      ORIGINALITY/VALUE: This paper is one of the first to address the unique issues of
      implementing lean to a healthcare setting in a developing country.

PMID- 25751250
TI  - Biased assimilation and need for closure: examining the effects of mixed blogs on
      vaccine-related beliefs.
AB  - This study examines the effect of mixed online information, in the form of user
      generated blogs, related to the HPV vaccine on perceived efficacy and safety of
      this vaccine. Guided by the theoretical frameworks of biased assimilation and
      need for closure, this research hypothesizes that exposure to mixed blogs about
      the HPV vaccine will lead to polarization of HPV vaccine-related beliefs among
      individuals with opposing prior opinions about vaccination and that the
      polarizing effects will be most pronounced among those high in need for closure.
      A controlled experiment (N = 338) found support for the hypotheses with regard to
      efficacy beliefs but not with regard to safety beliefs. Implications for health
      communication research and practice are discussed. 

PMID- 25751251
TI  - The 'W' prawn-trawl with emphasised drag-force transfer to its centre line to
      reduce overall system drag.
AB  - For prawn trawling systems, drag reduction is a high priority as the trawling
      process is energy intensive. Large benefits have occurred through the use of
      multiple-net rigs and thin twine in the netting. An additional positive effect of
      these successful twine-area reduction strategies is the reduced amount of otter
      board area required to spread the trawl systems, which leads to further drag
      reduction. The present work investigated the potential of redirecting the drag
      strain within a prawn trawl away from the wings and the otter boards to the
      centre line of the trawl, where top and bottom tongues have been installed, with
      an aim to minimise the loading/size of the otter boards required to spread the
      trawl. In the system containing the new 'W' trawl, the drag redirected to the
      centre-line tongues is transferred forward through a connected sled and towing
      wires to the trawler. To establish the extent of drag redirection to the centre
      line tongues and the relative drag benefits of the new trawl system, conventional
      and 'W' trawls of 3.65 m headline length were tested firstly over a range of
      spread ratios in the flume tank, and subsequently at optimum spread ratio in the
      field. The developed 'W' trawl effectively directed 64% of netting-drag off the
      wings and onto the centre tongues, which resulted in drag savings in the field of
      ~20% for the associated 'W' trawl/otter-board/sled system compared to the
      traditional trawl/otter-board arrangement in a single trawl or twin rig
      configuration. Furthermore, based on previously published data, the new trawl
      when used in a twin rig system is expected to provide approximately 12% drag
      reduction compared to quad rig. The twin 'W' trawl system also has benefits over
      quad rig in that a reduced number of cod-end/By-catch Reduction Device units need
      to be installed and attended each tow. 

PMID- 25751252
TI  - Socioeconomic determinants of bullying in the workplace: a national
      representative sample in Japan.
AB  - Bullying in the workplace is an increasingly recognized threat to employee
      health. We sought to test three hypotheses related to the determinants of
      workplace bullying: power distance at work; safety climate; and frustration
      related to perceived social inequality. A questionnaire survey was administered
      to a nationally representative community-based sample of 5,000 residents in Japan
      aged 20-60 years. The questionnaire included questions about employment,
      occupation, company size, education, household income, and subjective social
      status (SSS). We inquired about both the witnessing and personal experience of
      workplace bullying during the past 30 days. Among 2,384 respondents, data were
      analyzed from 1,546 workers. Multiple logistic regression analyses were used to
      examine the social determinants of workplace bullying. Six percent and 15 percent
      of the total sample reported experiencing or witnessing workplace bullying,
      respectively. After adjusting for gender and age, temporary employees (Odds Ratio
      [OR]: 2.45 [95% Confidence Interval (CI) = 1.03-5.85]), junior high school
      graduates (OR: 2.62 [95%CI: 1.01-6.79]), workers with lowest household income
      (OR: 4.13 [95%CI:1.58-10.8]), and workers in the lowest SSS stratum (OR: 4.21
      [95%CI:1.66-10.7]) were at increased risk of experiencing workplace bullying.
      When all variables were entered simultaneously in the model, a significant
      inverse association was observed between higher SSS and experiencing bullying (p
      = 0.002). Similarly in terms of witnessing bullying; SSS was significantly
      inversely associated (p = 0.017) while temporary employees reported a
      significantly higher risk of witnessing bullying compared to permanent workers
      (OR: 2.25 [95%CI:1.04 to 4.87]). The significant association between SSS and
      experiencing/witnessing workplace bullying supports the frustration hypothesis.
      The power distance hypothesis was also partly supported by the finding that
      temporary employees experienced a higher prevalence of workplace bullying. 

PMID- 25751253
TI  - A comparison of genetic variants between proficient low- and high-risk sport
      participants.
AB  - Athletes participating in high-risk sports consistently report higher scores on
      sensation-seeking measures than do low-risk athletes or non-athletic controls. To
      determine whether genetic variants commonly associated with sensation seeking
      were over-represented in such athletes, proficient practitioners of high-risk (n
      = 141) and low-risk sports (n = 132) were compared for scores on sensation
      seeking and then genotyped at 33 polymorphic loci in 14 candidate genes. As
      expected, athletes participating in high-risk sports score higher on sensation
      seeking than did low-risk sport athletes (P < .01). Genotypes were associated
      with high-risk sport participation for two genes (stathmin, (P = .004) and brain
      derived neurotrophic factor (P = .03)) as well as when demographically matched
      subsets of the sport cohorts were compared (P < .05); however, in all cases,
      associations did not survive correction for multiple testing. 

PMID- 25751254
TI  - Viable bacteria associated with red blood cells and plasma in freshly drawn blood
      donations.
AB  - OBJECTIVES: Infection remains a leading cause of post-transfusion mortality and
      morbidity. Bacterial contamination is, however, detected in less than 0.1% of
      blood units tested. The aim of the study was to identify viable bacteria in
      standard blood-pack units, with particular focus on bacteria from the oral
      cavity, and to determine the distribution of bacteria revealed in plasma and in
      the red blood cell (RBC)-fraction. DESIGN: Cross-sectional study. Blood were
      separated into plasma and RBC-suspensions, which were incubated anaerobically or
      aerobically for 7 days on trypticase soy blood agar (TSA) or blue lactose plates.
      For identification colony PCR was performed using primers targeting 16S rDNA.
      SETTING: Blood donors attending Capital Region Blood Bank, Copenhagen University
      Hospital, Rigshospitalet, Hvidovre, Denmark, October 29th to December 10th 2013.
      PARTICIPANTS: 60 donors (>=50 years old), self-reported medically healthy.
      RESULTS: Bacterial growth was observed on plates inoculated with plasma or RBCs
      from 62% of the blood donations. Growth was evident in 21 (35%) of 60 RBC
      fractions and in 32 (53%) of 60 plasma-fractions versus 8 of 60 negative controls
      (p = 0.005 and p = 2.6x10-6, respectively). Propionibacterium acnes was found in
      23% of the donations, and Staphylococcus epidermidis in 38%. The majority of
      bacteria identified in the present study were either facultative anaerobic
      (59.5%) or anaerobic (27.8%) species, which are not likely to be detected during
      current routine screening. CONCLUSIONS: Viable bacteria are present in blood from
      donors self-reported as medically healthy, indicating that conventional test
      systems employed by blood banks insufficiently detect bacteria in plasma. Further
      investigation is needed to determine whether routine testing for anaerobic
      bacteria and testing of RBC-fractions for adherent bacteria should be
      recommended.

PMID- 25751256
TI  - Recent Developments in Film and Gas Research in Modified Atmosphere Packaging of
      Fresh Foods.
AB  - Due to the rise of consumer's awareness of fresh foods to health, in the past few
      years, the consumption of fresh and fresh-cut produces has increased sturdily.
      Modified atmosphere packaging (MAP) possesses a potential to become one of the
      most appropriate technologies for packaging fresh and fresh-cut produces. The MAP
      has advantages of extending the shelf-life, preserving or stabilizing the desired
      properties of fresh produces, and convenience in handing and distribution. The
      success of MAP-fresh foods depends on many factors including types of fresh
      foods, storage temperature and humidity, gas composition, and the characteristics
      of package materials. This paper reviews the recent developments highlighting the
      most critical factors of film and gas on the quality of MAP fresh foods. Although
      the innovations and development of food packaging technology will continue to
      promote the development of novel MAP, concentrated research and endeavors from
      scientists and engineers are still important to the development of MAP that
      focuses on consumers' requirements, enhancing product quality, environmental
      friendly design, and cost-effective application. 

PMID- 25751255
TI  - The cell cycle regulator CCDC6 is a key target of RNA-binding protein EWS.
AB  - Genetic translocation of EWSR1 to ETS transcription factor coding region is
      considered as primary cause for Ewing sarcoma. Previous studies focused on the
      biology of chimeric transcription factors formed due to this translocation.
      However, the physiological consequences of heterozygous EWSR1 loss in these
      tumors have largely remained elusive. Previously, we have identified various
      mRNAs bound to EWS using PAR-CLIP. In this study, we demonstrate CCDC6, a known
      cell cycle regulator protein, as a novel target regulated by EWS. siRNA mediated
      down regulation of EWS caused an elevated apoptosis in cells in a CCDC6-dependant
      manner. This effect was rescued upon re-expression of CCDC6. This study provides
      evidence for a novel functional link through which wild-type EWS operates in a
      target-dependant manner in Ewing sarcoma. 

PMID- 25751258
TI  - Antiviral medication in sexually transmitted diseases. Part II: HIV.
AB  - This is a second part of a review under a main title Antiviral medication in
      sexually transmitted diseases. In the part we published in Mini Rev Med Chem.
      2013,13(13):1837-45, we have described mechanisms of action and mechanism of
      resistance to antiviral agents used in genital herpes and genital HPV infection.
      The Part II review focuses on therapeutic options in HIV infection. In 1987, 6
      years after the recognition of AIDS, the FDA approved the first drug against HIV-
      zidovudine. Since then a lot of antiretroviral drugs are available. The most
      effective treatment for HIV is highly active antiretroviral therapy--a
      combination of several antiretroviral medicines that cause a reduction of HIV
      blood concentration and often results in substantial recovery of impaired
      immunologic function. At present, there are over 20 drugs licensed and used for
      the treatment of HIV/AIDS, and these drugs are divided into one of six classes.
      Investigational agents include GS-7340, the prodrug of tenofovir and BMS-663068-
      the first in a novel class of drugs that blocks the binding of the HIV gp120 to
      the CD4 receptor.

PMID- 25751257
TI  - Cytoplasmic expression of pontin in renal cell carcinoma correlates with tumor
      invasion, metastasis and patients' survival.
AB  - Renal cell carcinoma (RCC) is the most lethal of all genitourinary malignancies.
      Distant metastasis represents the major cause of death in patients with RCC.
      Recent studies have implicated the AAA+ ATPase pontin in many cellular activities
      that are highly relevant to carcinogenesis. In this study, we demonstrate for the
      first time that pontin was up-regulated in RCC, and plays a previously unknown
      pro-invasive role in the metastatic progression of RCC through epithelial-to
      mesenchymal transition (EMT) pathway. 28 pairs of freshly frozen clear cell RCC
      samples and the matched normal renal tissues analyzed by quantitative RT-PCR and
      western blotting demonstrated that pontin was up-regulated in clear cell RCC
      tissues than in normal renal tissues. In addition, immunohistochemistry was used
      to evaluate subcellular pontin expression in 95 RCC patients, and found that
      overexpression of pontin in cytoplasm positively correlated with the metastatic
      features, predicting unfavorable outcomes of RCC patients. Furthermore, in vitro
      experiments show pontin was predominantly expressed in cytoplasm of RCC cell
      lines, and a significant suppression of cell migration and invasion in pontin
      siRNA treated RCC cell lines was observed. Mechanistic studies show that pontin
      depletion up-regulated the E-cadherin protein and down-regulated vimentin
      protein, and decreased nuclear beta-catenin expression, suggesting the
      involvement of EMT in pontin induced metastatic progression. Together, our data
      suggest pontin as a potential prognostic biomarker in RCC, and provide new
      promising therapeutic targets for clinical intervention of kidney cancers. 

PMID- 25751259
TI  - Predicting the druggability of protein-protein interactions based on sequence and
      structure features of active pockets.
AB  - Protein-protein interactions (PPIs) are becoming highly attractive targets for
      drug discovery. Motivated by the rapid accumulation of PPI data in public
      database and the success stories concerning the targeting of PPIs, a machine
      learning method based on sequence and structure properties was developed to
      access the druggability of PPIs. Here, a comprehensive non-redundant set of 34
      druggable and 122 less druggable PPIs were firstly presented from the perspective
      of pockets. When tested by outer 5-fold cross-validation, the most representative
      model in discriminating the druggable PPIs from the less-druggable ones yielded
      an average accuracy of 88.24% (sensitivity of 82.38% and specificity of 92.00%).
      Moreover, a promising result was also obtained for the independent test set.
      Compared to other methods, the method gives a comparative performance, which is
      most likely due to the construction of a training set that encompasses less
      druggable PPIs and also the information of active pockets that have evolved to
      bind a natural ligand. 

PMID- 25751260
TI  - Enhancing glucose sensor models: modeling the drop-outs.
AB  - BACKGROUND: Computer simulation environments have been used in the development of
      many artificial pancreas systems. A glucose sensor model is an essential part of
      these environments, and different models have been proposed. However, not one of
      these models accounts for drop-outs of sensor readings, a well-known phenomenon
      caused by physical pressure on the sensor site. In this work, we have proposed an
      enhanced model that accounts for drop-outs and demonstrated its improvement over
      the existing one-compartment model. MATERIALS AND METHODS: Potential drop-outs
      were augmented to the existing model, and their incidences and magnitudes were
      estimated simultaneously with the model parameters using the Bayesian approach.
      Drop-outs and model parameters were estimated from data collected from 15
      subjects with type 1 diabetes who underwent an artificial pancreas study. Model
      fitting and parameter estimates were contrasted between the enhanced model and
      the existing one-compartment model. RESULTS: Both models achieved similar
      parameter estimates (P=not significant) and were all physiologically plausible.
      The enhanced model further estimated 1.71 drop-outs per day, which improved model
      fit (weighted residual reduced from [minimum -4%, maximum 3%] to [-3%, 2%]) and
      reduced significantly the deviance information criteria from 2739.72 to 1456.00.
      CONCLUSIONS: The enhanced model improves fitting of glucose levels and should
      allow more realistic simulations that assesses artificial pancreas systems.

PMID- 25751261
TI  - Quantitative profiling of colorectal cancer-associated bacteria reveals
      associations between fusobacterium spp., enterotoxigenic Bacteroides fragilis
      (ETBF) and clinicopathological features of colorectal cancer.
AB  - Various studies have presented clinical or in vitro evidence linking bacteria to
      colorectal cancer, but these bacteria have not previously been concurrently
      quantified by qPCR in a single cohort. We quantify these bacteria (Fusobacterium
      spp., Streptococcus gallolyticus, Enterococcus faecalis, Enterotoxigenic
      Bacteroides fragilis (ETBF), Enteropathogenic Escherichia coli (EPEC), and afaC-
      or pks-positive E. coli) in paired tumour and normal tissue samples from 55
      colorectal cancer patients. We further investigate the relationship between a)
      the presence and b) the level of colonisation of each bacterial species with site
      and stage of disease, age, gender, ethnicity and MSI-status. With the exception
      of S. gallolyticus, we detected all bacteria profiled here in both tumour and
      normal samples at varying frequencies. ETBF (FDR = 0.001 and 0.002 for normal and
      tumour samples) and afaC-positive E. coli (FDR = 0.03, normal samples) were
      significantly enriched in the colon compared to the rectum. ETBF (FDR = 0.04 and
      0.002 for normal and tumour samples, respectively) and Fusobacterium spp. (FDR =
      0.03 tumour samples) levels were significantly higher in late stage (III/IV)
      colorectal cancers. Fusobacterium was by far the most common bacteria detected,
      occurring in 82% and 81% of paired tumour and normal samples. Fusobacterium was
      also the only bacterium that was significantly higher in tumour compared to
      normal samples (p = 6e-5). We also identified significant associations between
      high-level colonisation by Fusobacterium and MSI-H (FDR = 0.05), age (FDR = 0.03)
      or pks-positive E. coli (FDR = 0.01). Furthermore, we exclusively identified
      atypical EPEC in our cohort, which has not been previously reported in
      association with colorectal cancer. By quantifying colorectal cancer-associated
      bacteria across a single cohort, we uncovered inter- and intra-individual
      patterns of colonization not previously recognized, as well as important
      associations with clinicopathological features, especially in the case of
      Fusobacterium and ETBF. 

PMID- 25751262
TI  - Extracellular superoxide dismutase regulates the expression of small gtpase
      regulatory proteins GEFs, GAPs, and GDI.
AB  - Extracellular superoxide dismutase (SOD3), which catalyzes the dismutation of
      superoxide anions to hydrogen peroxide at the cell membranes, regulates the
      cellular growth in a dose-dependent manner. This enzyme induces primary cell
      proliferation and immortalization at low expression levels whereas it activates
      cancer barrier signaling through the p53-p21 pathway at high expression levels,
      causing growth arrest, senescence, and apoptosis. Because previous reports
      suggested that the SOD3-induced reduction in the rates of cellular growth and
      migration also occurred in the absence of functional p53 signaling, in the
      current study we investigated the SOD3-induced growth-suppressive mechanisms in
      anaplastic thyroid cancer cells. Based on our data, the robust over-expression of
      SOD3 increased the level of phosphorylation of the EGFR, ERBB2, RYK, ALK, FLT3,
      and EPHA10 receptor tyrosine kinases with the consequent downstream activation of
      the SRC, FYN, YES, HCK, and LYN kinases. However, pull-down experiments focusing
      on the small GTPase RAS, RAC, CDC42, and RHO revealed a reduced level of growth
      and migration signal transduction, such as the lack of stimulation of the mitogen
      pathway, in the SOD3 over-expressing cells, which was confirmed by MEK1/2 and
      ERK1/2 Western blotting analysis. Interestingly, the mRNA expression analyses
      indicated that SOD3 regulated the expression of guanine nucleotide-exchange
      factors (RHO GEF16, RAL GEF RGL1), GTPase-activating proteins (ARFGAP ADAP2, RAS
      GAP RASAL1, RGS4), and a Rho guanine nucleotide-disassociation inhibitor (RHO GDI
      2) in a dose dependent manner, thus controlling signaling through the small G
      protein GTPases. Therefore, our current data may suggest the occurrence of dose
      dependent SOD3-driven control of the GTP loading of small G proteins indicating a
      novel growth regulatory mechanism of this enzyme. 

PMID- 25751263
TI  - Of paleo-genes and Perch: what if an "alien" is actually a native?
AB  - Documenting whether a biotic taxon is native or alien to an ecosystem has
      theoretical value for ecological and evolutionary studies, and has practical
      value because it can potentially identify a taxon as a desirable component of an
      ecosystem or target it for removal. In some cases, however, such background
      information is inadequate or unavailable. Here we use paleo-DNA to re-evaluate
      the historical status of yellow perch in the 6 million acre Adirondack State Park
      of northern New York. Yellow perch DNA in a 2200-year sediment record reveals a
      long-term native status for these supposedly alien fish and challenges
      assumptions that they necessarily exclude native trout from upland lakes. Similar
      approaches could be applied to other species with uncertain historical
      distributions and could help to identify unrecognized pockets of biodiversity. 

PMID- 25751264
TI  - Disparities in access to healthy and unhealthy foods in central Massachusetts:
      implications for public health policy.
AB  - OBJECTIVES: To analyze geographic and income disparities in access to healthy
      foods in central Massachusetts. METHODS: We surveyed 106 (92% of all) food stores
      longitudinally in the study area between 2007 and 2010. We analyzed the
      geographic and temporal variations in community- and store-level healthy food
      availability indices (HFAI) and unhealthy food availability indices (UFAI)
      overall and by select store and community characteristics. RESULTS: Twenty-seven
      of 68 communities in the study area (39.7%) had no food store and 5 (8.3%) had
      one or few stores with very limited availability of healthy foods, affecting
      23.7% of the county population. Lack of food stores was associated strongly with
      lower housing density and upper tertile of median household income. About 45% of
      the surveyed stores had inadequate availabilities of healthy food. Store-level
      HFAI and UFAI scores were highly correlated, and higher among larger stores
      affiliated with a chain (vs independent). Though healthy foods were usually most
      available in larger stores, unhealthy foods were widely available in all stores.
      CONCLUSIONS: Over half of central Massachusetts communities, mostly rural and
      small, had either no food store or few stores with limited availabilities of
      healthy foods. Immediate policy interventions on the food environment are
      necessary in these communities. Further, without examining what is actually sold
      in stores, analysis of disparities in access to healthy food relies on the number
      of food stores, which can lead to a distorted picture of accessibility and
      mislead community health policies.

PMID- 25751265
TI  - Self-Reported Psychopathology, Trauma Symptoms, and Emotion Coping Among Child
      Suicide Attempters and Ideators: An Exploratory Study of Young Children.
AB  - This study examined self-reported psychopathology, trauma symptoms, and emotion
      coping in 7 to 12 year old children with suicidal ideation and attempts. This
      study compared 70 psychiatric inpatient children with current suicidal ideation
      to 59 psychiatric inpatient children with recent suicide attempts on measures of
      depression, anxiety, anger, emotional intelligence, and family/contextual
      factors. Results revealed greater self-reported anger as well as psychological
      distress associated with traumatic experiences (dissociation, anger, depression),
      among children who attempted suicide, in addition to increased reports of special
      education utilization, when compared to ideators only. These relationships were
      not affected by age or gender. Overall, the findings suggest self-reports of
      younger children who attempt suicide share similarities with older children and
      adolescent attempters, when compared with ideators who do not attempt.
      Implications for assessment and treatment are discussed. 

PMID- 25751266
TI  - Deficiency in Th2 cytokine responses exacerbate orthopoxvirus infection.
AB  - Ectromelia virus (ECTV) causes mousepox in mice, a disease very similar to
      smallpox in humans. ECTV and variola virus (VARV), the agent of smallpox, are
      closely related orthopoxviruses. Mousepox is an excellent small animal model to
      study the genetic and immunologic basis for resistance and susceptibility of
      humans to smallpox. Resistance to mousepox is dependent on a strong polarized
      type 1 immune response, associated with robust natural killer (NK) cell,
      cytotoxic T lymphocyte (CTL) and gamma interferon (IFN-gamma) responses. In
      contrast, ECTV-susceptible mice generate a type 2 response, associated with weak
      NK cell, CTL and IFN-gamma responses but robust IL-4 responses. Nonetheless,
      susceptible strains infected with mutant ECTV lacking virus-encoded IFN-gamma
      binding protein (vIFN-gammabp) (ECTV-IFN-gammabpDelta) control virus replication
      through generation of type 1 response. Since the IL-4/IL-13/STAT-6 signaling
      pathways polarize type 2/T helper 2 (Th2) responses with a corresponding
      suppression of IFN-gamma production, we investigated whether the combined absence
      of vIFN-gammabp, and one or more host genes involved in Th2 response development,
      influence generation of protective immunity. Most mutant mouse strains infected
      with wild-type (WT) virus succumbed to disease more rapidly than WT animals.
      Conversely, the disease outcome was significantly improved in WT mice infected
      with ECTV-IFN-gammabpDelta but absence of IL-4/IL-13/STAT-6 signaling pathways
      did not provide any added advantage. Deficiency in IL-13 or STAT-6 resulted in
      defective CTL responses, higher mortality rates and accelerated deaths.
      Deficiencies in IL-4/IL-13/STAT-6 signaling pathways significantly reduced the
      numbers of IFN-gamma producing CD4 and CD8 T cells, indicating an absence of a
      switch to a Th1-like response. Factors contributing to susceptibility or
      resistance to mousepox are far more complex than a balance between Th1 and Th2
      responses. 

PMID- 25751268
TI  - Recent developments with metalloprotease inhibitor class of drug candidates for
      botulinum neurotoxins.
AB  - Botulinum Neurotoxins are the most poisonous of all toxins with lethal dose in
      nanogram quantities. They are potential biological warfare and bioterrorism
      agents due to their high toxicity and ease of preparation. On the other hand
      BoNTs are also being increasingly used for therapeutic and cosmetic purposes, and
      with that the chances of accidental overdose are increasing. And despite the
      potential damage they could cause to human health, there are no post-intoxication
      drugs available so far. But progress is being made in this direction. The crystal
      structures in native form and bound with substrate peptides have been determined,
      and these are enabling structure-based drug discovery possible. High throughput
      assays have also been designed to speed up the screening progress. Substrate
      based and small molecule inhibitors have been identified. But turning high
      affinity inhibitors into clinically viable drug candidates has remained a
      challenge. We discuss here the latest developments and the future challenges in
      drug discovery for Botulinum neurotoxins. 

PMID- 25751267
TI  - HIV-Enhancing Factors Are Secreted by Reproductive Epithelia upon Inoculation
      with Bacterial Vaginosis-Associated Bacteria.
AB  - Bacterial vaginosis is a common reproductive infection in which commensal vaginal
      lactobacilli are displaced by a mixed population of pathogenic bacteria.
      Bacterial vaginosis increases susceptibility to HIV, and it has been suggested
      that host innate immune responses to pathogenic bacteria contribute to enhanced
      infection, yet the cellular mechanisms mediating the increased HIV susceptibility
      remain uncharacterized. We evaluated the HIV-enhancing effects of bacterial
      vaginosis by inoculating endocervical epithelia with Atopobium vaginae, a
      bacterial vaginosis-associated bacteria, and assaying secreted factors for HIV
      enhancing activity. When epithelia and A. vaginae were cocultured, we observed
      increased HIV-enhancing activity mediated by secreted low molecular weight
      factors. From this complex mixture we identified several upregulated host
      proteins, which functioned in combination to enhance HIV infection. These studies
      suggest that the host immune response to bacterial vaginosis-associated bacteria
      results in the release of HIV-enhancing factors. The combined activity of
      bacterial vaginosis-induced proteins likely mediates HIV enhancement. 

PMID- 25751269
TI  - Ion channels as medicinal targets of biological toxins: the impact of automated
      patch-clamp electrophysiology.
AB  - Patch-Clamp electrophysiology, the "gold standard" for the functional study of
      ion channels has become automated. This innovative technology, already over a
      decade old, has revolutionized the strategies for the search of medicinal
      compounds which now can be screened at unprecedented speed, approaching the high
      throughput standards required by primary screening campaigns emblematic of the
      pharmaceutical and biotechnology industries. Consequently, an acceleration of the
      discovery and development of new drugs targeting ion channels is expected. These
      pore forming membrane proteins had been relegated as crucial therapeutic drug
      targets due to the difficulty of their experimental analysis. This new
      technological approach has begun to impact the finding of new toxins which are
      conspicuously relevant as medicinal agents given their extraordinary potency and
      specificity when acting upon ion channels. The introduction of automated patch
      clamp instrumentation to academic labs and institutions pursuing the finding of
      new pharmacological agents, peptide toxins in particular, will certainly enrich
      these scientific and technological fields by contributing with their always
      prolific generosity of originality and innovation. 

PMID- 25751270
TI  - Differential expression of lipid metabolism-related proteins in different breast
      cancer subtypes.
AB  - PURPOSE: This study aimed to determine the expression and clinical significance
      of proteins that are involved in lipid metabolism in human breast tumors.
      METHODS: Tumors from 476 breast cancer patients were used to construct tissue
      microarrays. Then, immunohistochemistry (IHC) for hormone-sensitive lipase (HSL),
      Perilipin 1 (PLIN1), fatty acid binding protein 4 (FABP4), carnitine
      palmitoyltransferase IA (CPT-1A), acyl-CoA oxidase 1 (ACOX-1), and fatty acid
      synthase (FASN) was performed on these microarrays. RESULTS: Breast tumors were
      classified into 4 subtypes: luminal A (n = 242; 50.8%), luminal B (n = 134;
      28.2%), human epidermal growth factor receptor 2 (HER2) (n = 50; 10.5%), and
      triple negative breast cancer (TNBC) (n = 50; 10.5%). The expression of PLIN1 (p
      < 0.001), FABP4 (p = 0.029), CPT-1A (p = 0.001), ACOX-1 (p < 0.001), and FASN (p
      < 0.001) differed significantly among these tumor subtypes. Notably, PLIN1, CPT
      1A, and FASN expression was highest in HER2 tumors and lowest in TNBC tumors.
      Similarly, the expression of FABP4 and ACOX-1 was highest in HER2 tumors and
      lowest in luminal A tumors. In addition, ACOX-1 positivity was associated with
      significantly shorter overall survival (p = 0.018). When tumor subtype was
      considered, FABP4 positivity was associated with significantly shorter disease
      free survival (p = 0.005) and overall survival (p = 0.041) in TNBC. CONCLUSION:
      Lipid metabolism-related proteins are differentially expressed in different IHC
      subtypes of breast cancer and some are associated with decreased survival rates.

PMID- 25751271
TI  - Fin spine bone resorption in atlantic bluefin tuna, Thunnus thynnus, and
      comparison between wild and captive-reared specimens.
AB  - Bone resorption in the first spine of the first dorsal fin of Atlantic bluefin
      tuna (ABFT) has long been considered for age estimation studies. In the present
      paper spine bone resorption was assessed in wild (aged 1 to 13 years) and captive
      reared (aged 2 to 11 years) ABFT sampled from the Mediterranean Sea. Total
      surface (TS), solid surface (SS) and reabsorbed surface (RS) were measured in
      spine transverse sections in order to obtain proportions of SS and RS. The spine
      section surface was found to be isometrically correlated to the fish fork length
      by a power equation. The fraction of solid spine bone progressively decreased
      according to a logarithmic equation correlating SS/TS to both fish size and age.
      The values ranged from 57% in the smallest examined individuals to 37% in the
      largest specimens. This phenomenon was further enhanced in captive-reared ABFT
      where SS/TS was 22% in the largest measured specimen. The difference between the
      fraction of SS of wild and captive-reared ABFT was highly significant. In each
      year class from 1- to 7-year-old wild specimens, the fraction of spine reabsorbed
      surface was significantly higher in specimens collected from March to May than in
      those sampled during the rest of the year. In 4-year-old fish the normal SS
      increase during the summer did not occur, possibly coinciding with their first
      sexual maturity. According to the correlations between SS/TS and age, the rate of
      spine bone resorption was significantly higher, even almost double, in captive
      reared specimens. This could be attributed to the wider context of systemic
      dysfunctions occurring in reared ABFT, and may be related to a number of factors,
      including nutritional deficiencies, alteration of endocrine profile, cortisol
      induced stress, and loss of spine functions during locomotion in rearing
      conditions. 

PMID- 25751272
TI  - Repeatability of quantitative sodium magnetic resonance imaging for estimating
      pseudo-intracellular sodium concentration and pseudo-extracellular volume
      fraction in brain at 3 T.
AB  - The purpose of this study is to assess the repeatability of the quantification of
      pseudo-intracellular sodium concentration (C1) and pseudo-extracellular volume
      fraction (alpha) estimated in brain in vivo using sodium magnetic resonance (MRI)
      at 3 T. Eleven healthy subjects were scanned twice, with two sodium MRI
      acquisitions (with and without fluid suppression by inversion recovery), and two
      double inversion recovery (DIR) proton MRI. DIR MRIs were used to create masks of
      gray and white matter (GM, WM), that were subsequently applied to the C1 and
      alpha maps calculated from sodium MRI and a tissue three-compartment model, in
      order to measure the distributions of these two parameters in GM, WM or full
      brain (GM+WM) separately. The mean, median, mode, standard deviation (std),
      skewness and kurtosis of the C1 and alpha distributions in whole GM, WM and full
      brain were calculated for each subject, averaged over all data, and used as
      parameters for the repeatability assessment. The coefficient of variation (CV)
      was calculated as a measure of reliability for the detection of intra-subject
      changes in C1 and alphafor each parameter, while intraclass correlation (ICC) was
      used as a measure of repeatability. It was found that the CV of most of the
      parameters was around 10-20% (except for C1 kurtosis which is about 40%) for C1
      and alpha measurements, and that ICC was moderate to very good (0.4 to 0.9) for
      C1 parameters and for some of the alpha parameters (mainly skewness and
      kurtosis). In conclusion, the proposed method could allow to reliably detect
      changes of 50% and above of the different measurement parameters of C1 and
      alphain neuropathologies (multiple sclerosis, tumor, stroke, Alzheimer's disease)
      compared to healthy subjects, and that skewness and kurtosis of the distributions
      of C1 and alphaseem to be the more sensitive parameters to these changes. 

PMID- 25751273
TI  - Within-trait heterogeneity in age group differences in personality domains and
      facets: implications for the development and coherence of personality traits.
AB  - The study investigated differences in the Five-Factor Model (FFM) domains and
      facets across adulthood. The main questions were whether personality scales
      reflected coherent units of trait development and thereby coherent personality
      traits more generally. These questions were addressed by testing if the
      components of the trait scales (items for facet scales and facets for domain
      scales) showed consistent age group differences. For this, measurement invariance
      (MI) framework was used. In a sample of 2,711 Estonians who had completed the NEO
      Personality Inventory 3 (NEO PI-3), more than half of the facet scales and one
      domain scale did not meet the criterion for weak MI (factor loading equality)
      across 12 age groups spanning ages from 18 to 91 years. Furthermore, none of the
      facet and domain scales met the criterion for strong MI (intercept equality),
      suggesting that items of the same facets and facets of the same domains varied in
      age group differences. When items were residualized for their respective facets,
      46% of them had significant (p < 0.0002) residual age-correlations. When facets
      were residualized for their domain scores, a majority had significant (p < 0.002)
      residual age-correlations. For each domain, a series of latent factors were
      specified using random quarters of their items: scores of such latent factors
      varied notably (within domains) in correlations with age. We argue that
      manifestations of aetiologically coherent traits should show similar age group
      differences. Given this, the FFM domains and facets as embodied in the NEO PI-3
      do not reflect aetiologically coherent traits. 

PMID- 25751275
TI  - Resolving the decision aid paradox.

PMID- 25751274
TI  - Amount of colicin release in Escherichia coli is regulated by lysis gene
      expression of the colicin E2 operon.
AB  - The production of bacteriocins in response to worsening environmental conditions
      is one means of bacteria to outcompete other microorganisms. Colicins, one class
      of bacteriocins in Escherichia coli, are effective against closely related
      Enterobacteriaceae. Current research focuses on production, release and uptake of
      these toxins by bacteria. However, little is known about the quantitative aspects
      of these dynamic processes. Here, we quantitatively study expression dynamics of
      the Colicin E2 operon in E. coli on a single cell level using fluorescence time
      lapse microscopy. DNA damage, triggering SOS response leads to the heterogeneous
      expression of this operon including the cea gene encoding the toxin, Colicin E2,
      and the cel gene coding for the induction of cell lysis and subsequent colicin
      release. Advancing previous whole population investigations, our time-lapse
      experiments reveal that at low exogenous stress levels all cells eventually
      respond after a given time (heterogeneous timing). This heterogeneous timing is
      lost at high stress levels, at which a synchronized stress response of all cells
      60 min after induction via stress can be observed. We further demonstrate, that
      the amount of colicin released is dependent on cel (lysis) gene expression,
      independent of the applied exogenous stress level. A heterogeneous response in
      combination with heterogeneous timing can be biologically significant. It might
      enable a bacterial population to endure low stress levels, while at high stress
      levels an immediate and synchronized population wide response can give single
      surviving cells of the own species the chance to take over the bacterial
      community after the stress has ceased. 

PMID- 25751276
TI  - Technology whitespaces India should focus: a comparative anti-cancer patent
      rational analysis of Indian and international public funded universities.
AB  - The article reported an in-depth comparative technology analysis of 1708 Anti
      cancer patents from top 20 international universities and leading 10 Indian
      public funded organization and research institutes. The study segregated pioneer
      universities vs. technologies used in the field of Anticancer research at a level
      of drug discovery, development, diagnosis and treatment, which are illustrated in
      the form of novel substantive patent landscape maps. The reported competitive
      intelligent maps identified genetics, composition and synthetic compounds as
      dominating technologies; followed by natural extracts, combination and drug
      delivery systems as upcoming technologies. The least number of patents were
      reported by surgical apparatus, targeted therapy and animal models. In addition,
      the study analysed the key technologies followed by Indian universities in
      comparison to the international universities, to identify the overlooked
      technologies by the Indian public funded institutes. In an ever changing
      competitive world, it is essential for every university to have their own
      research plan and thrust areas; but at the same time, it is equally important for
      any organisation to have an idea of their competitor's research plan as well. So,
      the article suggested Indian institutes to focus on the latest emerging Anti
      cancer technology trends, which are in practice by the international
      universities. Concurrently, this study may be a landmark indication for Indian
      public funded universities and institutes, calling for a U-turn from their
      traditional approaches. 

PMID- 25751278
TI  - Kinetically Stable Lanthanide Complexes Displaying Exceptionally High Quantum
      Yields upon Long-Wavelength Excitation: Synthesis, Photophysical Properties, and
      Solution Speciation.
AB  - We demonstrate how highly emissive, kinetically stable complexes can be prepared
      using the macrocyclic scaffold of DO3A bearing coordinating aryl ketones as
      highly effective sensitizing chromophores. In the europium complexes, high
      quantum yields (up to 18% in water) can be combined with long-wavelength
      excitation (370 nm). The behavior in solution upon variation of pH, studied by
      means of UV-vis absorption, emission, and NMR spectroscopies, reveals that the
      nature of the chromophore can give rise to pH-dependent behavior as a consequence
      of deprotonation adjacent to the carbonyl group. Knowledge of the molecular
      speciation in solution is therefore critical when assessing the luminescence
      properties of such complexes. 

PMID- 25751280
TI  - Genetic Polymorphism of the Serotonin Transporter Gene, SLC6A4 rs16965628, Is
      Associated with Obsessive Compulsive Disorder.
AB  - Obsessive compulsive disorder (OCD) is a psychiatric disorder characterized by
      obsessive ideas and compulsive behaviors. Genetic studies have centered on
      candidate genes involved in OCD etiology related to serotonergic and dopaminergic
      systems. In this study, the relationship between cathechol-O-methyltransferase
      (COMT) -287A/G (rs2097063), serotonin transporters 5-HTTLPR I/D, and SLC6A4
      rs16965628 polymorphisms in 80 OCD patients and 100 healthy controls was
      determined. Patients and controls were genotyped for COMT rs2097063 and SLC6A4
      rs16965628 polymorphisms by real-time polymerase chain reaction (PCR). The 5
      HTTLPR I/D polymorphism was genotyped using PCR and agarose gel electrophoresis.
      Severity of symptoms was checked with a Yale-Brown Obsession Compulsion Scale (Y
      BOCS). When the OCD group and controls were compared, no significant difference
      was found between COMT -287A/G (rs2097063), 5-HTTLPR I/D polymorphisms, and OCD.
      However, a significant difference was found between 5-HTT rs16965628 polymorphism
      and OCD (p=0.025, OR=3.43, 95% CI 1.41-10.35). In addition, the G allele
      frequency was found to be higher for rs16965628 in the OCD group. No significant
      difference was observed between COMT -287A/G (rs2097063), SLC6A4 rs16965628, and
      5-HTTLPR I/D polymorphisms and Y-BOCS scores (p>0.05). There was also lack of
      correlation between Yale-Brown scores and gender of OCD patients. On the other
      hand, combined genotypes of SLC6A4 rs16965628 GG+GC were found to be risk factors
      for OCD development (p=0.02, OR=3.464; 95% CI 1.214-9.883) in logistic regression
      analysis adjusted for age and gender. Our findings suggest that subjects carrying
      the G allele of rs16965628 have genetic susceptibility to OCD. These data are the
      first to suggest that polymorphism in serotonin transporter (rs16965628) is
      associated with the development of OCD in the Turkish population. 

PMID- 25751279
TI  - Pharmacological folding chaperones act as allosteric ligands of Frizzled4.
AB  - Upon binding, ligands can chaperone their protein targets by preventing them from
      misfolding and aggregating. Thus, an organic molecule that works as folding
      chaperone for a protein might be its specific ligand, and, similarly, the
      chaperone potential could represent an alternative readout in a molecular
      screening campaign toward the identification of new hits. Here we show that small
      molecules selected for acting as pharmacological chaperones on a misfolded mutant
      of the Frizzled4 (Fz4) receptor bind and modulate wild-type Fz4, representing
      what are to our knowledge the first organic ligands of this until-now-undruggable
      GPCR. The novelty and the advantages of the screening platform, the allosteric
      binding site addressed by these new ligands and the mechanism they use to
      modulate Fz4 suggest new avenues for development of inhibitors of the Wnt-beta
      catenin pathway and for drug discovery. 

PMID- 25751281
TI  - Decitabine nanoconjugate sensitizes human glioblastoma cells to temozolomide.
AB  - In this study, we developed and characterized a delivery system for the
      epigenetic demethylating drug, decitabine, to sensitize temozolomide-resistant
      human glioblastoma multiforme (GBM) cells to alkylating chemotherapy. A
      poly(lactic-co-glycolic acid) (PLGA) and poly(ethylene glycol) (PEG) based
      nanoconjugate was fabricated to encapsulate decitabine and achieved a better
      therapeutic response in GBM cells than that with the free drug. After synthesis,
      the highly efficient uptake process and intracellular dynamics of this
      nanoconjugate were monitored by single-molecule fluorescence tools. Our
      experiments demonstrated that, under an acidic pH due to active glycolysis in
      cancer cells, the PLGA-PEG nanovector could release the conjugated decitabine at
      a faster rate, after which the hydrolyzed lactic acid and glycolic acid would
      further acidify the intracellular microenvironment, thus providing positive
      feedback to increase the effective drug concentration and realize growth
      inhibition. In temozolomide-resistant GBM cells, decitabine can potentiate the
      cytotoxic DNA alkylation by counteracting cytosine methylation and reactivating
      tumor suppressor genes, such as p53 and p21. Owing to the excellent
      internalization and endolysosomal escape enabled by the PLGA-PEG backbone, the
      encapsulated decitabine exhibited a better anti-GBM potential than that of free
      drug molecules. Hence, the synthesized nanoconjugate and temozolomide could act
      in synergy to deliver a more potent and long-term antiproliferative effect
      against malignant GBM cells. 

PMID- 25751282
TI  - Mutation in CPT1C Associated With Pure Autosomal Dominant Spastic Paraplegia.
AB  - IMPORTANCE: The family of genes implicated in hereditary spastic paraplegias
      (HSPs) is quickly expanding, mostly owing to the widespread availability of next
      generation DNA sequencing methods. Nevertheless, a genetic diagnosis remains
      unavailable for many patients. OBJECTIVE: To identify the genetic cause for a
      novel form of pure autosomal dominant HSP. DESIGN, SETTING, AND PARTICIPANTS: We
      examined and followed up with a family presenting to a tertiary referral center
      for evaluation of HSP for a decade until August 2014. Whole-exome sequencing was
      performed in 4 patients from the same family and was integrated with linkage
      analysis. Sanger sequencing was used to confirm the presence of the candidate
      variant in the remaining affected and unaffected members of the family and screen
      the additional patients with HSP. Five affected and 6 unaffected participants
      from a 3-generation family with pure adult-onset autosomal dominant HSP of
      unknown genetic origin were included. Additionally, 163 unrelated participants
      with pure HSP of unknown genetic cause were screened. MAIN OUTCOME AND MEASURE:
      Mutation in the neuronal isoform of carnitine palmitoyl-transferase (CPT1C) gene.
      RESULTS: We identified the nucleotide substitution c.109C>T in exon 3 of CPT1C,
      which determined the base substitution of an evolutionarily conserved Cys residue
      for an Arg in the gene product. This variant strictly cosegregated with the
      disease phenotype and was absent in online single-nucleotide polymorphism
      databases and in 712 additional exomes of control participants. We showed that
      CPT1C, which localizes to the endoplasmic reticulum, is expressed in motor
      neurons and interacts with atlastin-1, an endoplasmic reticulum protein encoded
      by the ATL1 gene known to be mutated in pure HSPs. The mutation, as indicated by
      nuclear magnetic resonance spectroscopy studies, alters the protein conformation
      and reduces the mean (SD) number (213.0 [46.99] vs 81.9 [14.2]; P < .01) and size
      (0.29 [0.01] vs 0.26 [0.01]; P < .05) of lipid droplets on overexpression in
      cells. We also observed a reduction of mean (SD) lipid droplets in primary
      cortical neurons isolated from Cpt1c-/- mice as compared with wild-type mice (1.0
      [0.12] vs 0.44 [0.05]; P < .001), suggesting a dominant negative mechanism for
      the mutation. CONCLUSIONS AND RELEVANCE: This study expands the genetics of
      autosomal dominant HSP and is the first, to our knowledge, to link mutation in
      CPT1C with a human disease. The association of the CPT1C mutation with changes in
      lipid droplet biogenesis supports a role for altered lipid-mediated signal
      transduction in HSP pathogenesis.

PMID- 25751284
TI  - Impact of bentonite additions during vinification on protein stability and
      volatile compounds of Albarino wines.
AB  - Today, bentonite continues to be one of the most used products to remove proteins
      in white wines in order to avoid their precipitation in bottles. However,
      excessive use of bentonite has negative effects on the aroma of final wine, so
      the optimization of the dose and the time of its application are important for
      winemakers. This paper analyzes how applying an equal dose of bentonite at
      different stages (must clarification; beginning, middle, and end of fermentation)
      affects the macromolecular profile, protein stability, physical-chemical
      characteristics and aromatic profile of the wine obtained. The results showed the
      addition during fermentation (especially in the middle and at the end) reduced
      the total dose required for protein stabilization of Albarino wines and
      maintained the sensory characteristics of this variety. 

PMID- 25751283
TI  - Design and synthesis of norendoxifen analogues with dual aromatase inhibitory and
      estrogen receptor modulatory activities.
AB  - Both selective estrogen receptor modulators and aromatase inhibitors are widely
      used for the treatment of breast cancer. Compounds with both aromatase inhibitory
      and estrogen receptor modulatory activities could have special advantages for
      treatment of breast cancer. Our previous efforts led to the discovery of
      norendoxifen as the first compound with dual aromatase inhibitory and estrogen
      receptor binding activities. To optimize its efficacy and aromatase selectivity
      versus other cytochrome P450 enzymes, a series of structurally related
      norendoxifen analogues were designed and synthesized. The most potent compound,
      4'-hydroxynorendoxifen (10), displayed elevated inhibitory potency against
      aromatase and enhanced affinity for estrogen receptors when compared to
      norendoxifen. The selectivity of 10 for aromatase versus other cytochrome P450
      enzymes was also superior to norendoxifen. 4'-Hydroxynorendoxifen is therefore an
      interesting lead for further development to obtain new anticancer agents of
      potential value for the treatment of breast cancer. 

PMID- 25751285
TI  - Acetyl-L-carnitine in the treatment of peripheral neuropathic pain: a systematic
      review and meta-analysis of randomized controlled trials.
AB  - OBJECTIVE: Acetyl-L-carnitine (ALC), a constructive molecule in fatty acid
      metabolism, is an agent potentially effective for treating peripheral neuropathic
      pain (PNP). Its effect, however, remains uncertain. We aimed to access the
      efficacy and safety of ALC for the treatment of patients with PNP. METHODS: We
      searched MEDLINE (1996-2014), EMBase (1974-2014), and CENTRAL (May 2014) up to
      June 27, 2014 for randomized controlled trials (RCTs) comparing ALC with placebo
      or other active medications in diabetic and non-diabetic PNP patients that
      reported the change of pain using visual analogue scale (VAS). Mean difference
      (MD) and 95% confidence interval (CI) were used for pooling continuous data.
      RESULTS: Four RCTs comparing ALC with placebo and reporting in three articles (n
      = 523) were included. Compared with placebo, ALC significantly reduced VAS scores
      of PNP patients (MD of VAS, 1.20; 95% CI, 0.68-1.72, P <0.00001). In the subgroup
      analysis, the effect of ALC on VAS was similar in different administration routes
      (intramuscular-oral sequential subgroup: MD, 1.19; 95% CI, 0.34-2.04, P = 0.006;
      oral only subgroup: pooled MD, 1.15; 95%CI, 0.33-1.96, P = 0.006), and ALC
      appeared more effective in diabetic PNP patients than non-diabetic PNP patients
      (diabetic subgroup: MD, 1.47; 95%CI, 1.06-1.87, P <0.00001; non-diabetic
      subgroup: MD, 0.71; 95% CI, -0.01-1.43, P = 0.05). No severe adverse events were
      reported related to ALC. The common adverse events were pain, headache,
      paraesthesia, hyperesthesia, retching, biliary colic, and gastrointestinal
      disorders. The rates of total adverse events were similar in ALC and control
      group. CONCLUSION: The current evidence suggests that ALC has a moderate effect
      in reducing pain measured on VAS in PNP patients with acceptable safety. Larger
      trials with longer follow-up, however, are warranted to establish the effects.

PMID- 25751287
TI  - Simultaneous determination of creatinine and creatine in human serum by double
      spike isotope dilution liquid chromatography-tandem mass spectrometry (LC-MS/MS)
      and gas chromatography-mass spectrometry (GC-MS).
AB  - This work describes the first multiple spiking isotope dilution procedure for
      organic compounds using (13)C labeling. A double-spiking isotope dilution method
      capable of correcting and quantifying the creatine-creatinine interconversion
      occurring during the analytical determination of both compounds in human serum is
      presented. The determination of serum creatinine may be affected by the
      interconversion between creatine and creatinine during sample preparation or by
      inefficient chemical separation of those compounds by solid phase extraction
      (SPE). The methodology is based on the use differently labeled (13)C analogues
      ((13)C1-creatinine and (13)C2-creatine), the measurement of the isotopic
      distribution of creatine and creatinine by liquid chromatography-tandem mass
      spectrometry (LC-MS/MS) and the application of multiple linear regression. Five
      different lyophilized serum-based controls and two certified human serum
      reference materials (ERM-DA252a and ERM-DA253a) were analyzed to evaluate the
      accuracy and precision of the proposed double-spike LC-MS/MS method. The
      methodology was applied to study the creatine-creatinine interconversion during
      LC-MS/MS and gas chromatography-mass spectrometry (GC-MS) analyses and the
      separation efficiency of the SPE step required in the traditional gas
      chromatography-isotope dilution mass spectrometry (GC-IDMS) reference methods
      employed for the determination of serum creatinine. The analysis of real serum
      samples by GC-MS showed that creatine-creatinine separation by SPE can be a
      nonquantitative step that may induce creatinine overestimations up to 28% in
      samples containing high amounts of creatine. Also, a detectable conversion of
      creatine into creatinine was observed during sample preparation for LC-MS/MS. The
      developed double-spike LC-MS/MS improves the current state of the art for the
      determination of creatinine in human serum by isotope dilution mass spectrometry
      (IDMS), because corrections are made for all the possible errors derived from the
      sample preparation step. 

PMID- 25751286
TI  - Competition among Li(+), Na(+), K(+), and Rb(+) monovalent ions for DNA in
      molecular dynamics simulations using the additive CHARMM36 and Drude polarizable
      force fields.
AB  - In the present study we report on interactions of and competition between
      monovalent ions for two DNA sequences in MD simulations. Efforts included the
      development and validation of parameters for interactions among the first-group
      monovalent cations, Li(+), Na(+), K(+), and Rb(+), and DNA in the Drude
      polarizable and additive CHARMM36 force fields (FF). The optimization process
      targeted gas-phase QM interaction energies of various model compounds with ions
      and osmotic pressures of bulk electrolyte solutions of chemically relevant ions.
      The optimized ionic parameters are validated against counterion condensation
      theory and buffer exchange-atomic emission spectroscopy measurements providing
      quantitative data on the competitive association of different monovalent ions
      with DNA. Comparison between experimental and MD simulation results demonstrates
      that, compared to the additive CHARMM36 model, the Drude FF provides an improved
      description of the general features of the ionic atmosphere around DNA and leads
      to closer agreement with experiment on the ionic competition within the ion
      atmosphere. Results indicate the importance of extended simulation systems on the
      order of 25 A beyond the DNA surface to obtain proper convergence of ion
      distributions. 

PMID- 25751288
TI  - Effects of unilateral PEEP on biomechanics of both lungs during independent lung
      ventilation in patients anaesthetised for thoracic surgery.
AB  - BACKGROUND: Synchronous independent lung ventilation (ILV) is the treatment of
      choice for unilateral pathology of lung parenchyma. Numerous studies have
      documented the improved blood oxygenation and clinical efficacy of this
      procedure. The aim of the present study was to evaluate the effects of ILV on the
      selected biomechanical parameters of the lungs. METHOD: The study involved ASA I
      II patients undergoing thoracic surgery in the lateral decubitus position under
      the standard conditions of general anaesthesia with the thoracic cavity closed.
      ILV with equal separation of the tidal volume was performed with a prototype
      volume separator, using incremental a PEEP of 0-15 cm H2O in the dependent lung.
      Peak pressures, dynamic compliance and airway resistance of both lungs were
      evaluated. RESULTS: The study included 36 patients. In all of the patients, a
      PEEP of 5-15 cm H2O in one lung increased its peak pressures, dynamic compliance
      and resistances, and variably affected the biomechanical parameters of the other
      lung. Irrespective of patient positioning on the right or left side, the highest
      compliance was recorded at a PEEP of 10 cm H2O. CONCLUSIONS: In ILV, peak
      pressures and airway resistances are higher in the dependent lung compared to
      compliances in the non-dependent lung. ILV with a PEEP of 5-15 cm H2O increases
      the biomechanical parameters of the dependent lung while variably influencing the
      parameters in the non-dependent lung.

PMID- 25751289
TI  - Results of the severe sepsis registry in intensive care units in Poland from 2003
      2009.
AB  - BACKGROUND: Severe sepsis remains the most common cause of death in intensive
      care units (ICUs) according to many epidemiological studies. There are no data in
      Poland on the extent of severe sepsis cases treated in ICUs. The aim of the study
      was to analyse the course and outcome of severe sepsis patients treated in Polish
      ICUs. METHODS: In 2003, the internet-based severe sepsis registry was created as
      a multicentre observational research project. An online questionnaire was made
      accessible to ICUs participating in the study. Questionnaires were completed
      after the discharge of patients and included demographic data, clinical and
      microbiological information about the cause, course, treatment and outcome of
      septic patients. All data were given voluntarily and anonymously. RESULTS: During
      the 7-year period (2003-2009), 4999 cases of severe sepsis were registered for
      analysis. The mean age of septic patients was 57 years, and the majority of the
      patients were men (58%). The mean length of stay in the ICU was 10 days. A
      significant decrease in the mortality rate was observed from 54% in 2003 and 56%
      in 2004 to 46% in 2009 (P < 0.05). Most of the patients were admitted to the ICU
      for surgical reasons (56%), and intra-abdominal infections predominated (49%).
      Severe sepsis patients were admitted to ICUs in critical condition, and the
      majority of them (89%) had 3 or more organs dysfunction. The APACHE II score on
      admission was 26 points. Community acquired infections were the most frequent
      cause of severe sepsis (53%). Most of the pathogens responsible for infection
      were Gram-negative bacteria (58%). Gram-positive bacteria were identified in 34%
      of patients and fungi in 16%. A positive blood culture was detected in 41% of
      patients. Vasopressors were administered to most of the patients (86%). There was
      a marked increase in the frequency of administering noradrenaline and a decrease
      in administering dopamine. Renal replacement therapy was applied in 22% of the
      patients, and there was a marked increase in this type of therapy in the last two
      years of the study period. CONCLUSIONS: Patients with severe sepsis involved in
      the 7-year registry were critically ill in half of the cases because of intra
      abdominal infections, and the majority of them had multi-organ dysfunction. The
      mortality of registered patients was high, but it significantly decreased during
      the observation time. Based on the results obtained from this voluntary registry,
      the authors conclude that mandated sepsis registries should be established in
      Polish hospitals to improve the strategy of diagnosing and managing this
      syndrome.

PMID- 25751290
TI  - Cooled radiofrequency system relieves chronic knee osteoarthritis pain: the first
      case-series.
AB  - BACKGROUND: Knee osteoarthritis is a frequent cause of chronic knee pain.
      Therapeutic solutions include intra-articular injections with short-term pain
      relief and surgical therapy. Radiofrequency (RF) of genicular nerves has been
      previously reported with varying success. Cooling tissue adjacent to the
      electrode (cooled RF) increases the radius of lesion. We present here the first
      retrospective data on pain relief and changes in function after such cooled RF
      denervation. METHODS: We reviewed the records of nine patients with chronic knee
      pain who underwent cooled RF of genicular nerves. Visual analogue scale (VAS) and
      Western Ontario McMaster Universities OA index (WOMAC) were analysed. RESULTS: We
      observed an improvement in VAS pain scores 2 +/- 0.5 at one month, 2.3 +/- 0.7 at
      three months, 2.1 +/- 0.5 at six months, and 2.2 +/- 0.2 at 12 months after the
      procedure, and WOMAC score 20 +/- 2, at one month, 22 +/- 0.5 at three months, 21
      +/- 1.7 at six months, and 20 +/- 1.0 at 12 months. CONCLUSION: The majority of
      patients with chronic knee pain experienced a clinically relevant degree of pain
      relief and improved function following cooled RF of genicular nerves at one,
      three, six and 12 months follow-up.

PMID- 25751291
TI  - Ventilator-associated pneumonia monitoring according to the INICC project at one
      centre.
AB  - BACKGROUND: Pneumonia is a common complication of hospitalisation in severely ill
      patients who need mechanical ventilation. The aim of this study was to assess the
      usefulness of the International Nosocomial Infection Control Consortium programme
      for the surveillance of ventilator-associated pneumonia (VAP). METHODS: A
      prospective study (1 Jan 2012-30 June 2014) was conducted in the 20-bed ICU. The
      device utilisation ratios for lung ventilation and the frequency (density and
      incidence) and aetiology of VAP were estimated in ICU patients. RESULTS: From a
      total of 1097 patients, VAP infections were diagnosed in 93. Thirty percent of
      patients with VAP died. The incidence index was 8.47 per 100 admissions to the
      ICU. VAP infections accounted for 46% of the overall count of device-associated
      healthcare-associated infections. Mechanical ventilation was used in 71 +/- 8
      patients during the 11 862 patient days and 8425 ventilation days. The rate of
      VAP per 1000 ventilator days was 11.15/9.34 /10.23 in years 2012/2013/2014 (half
      a year), respectively. The main VAP pathogens were Acinetobacter baumannii (45%)
      and Pseudomonas aeruginosa (17%). CONCLUSION: During the reported time span, the
      incidence of VAP was lower than in the INICC report (2007-2012), but it was
      tenfold higher than in the NHSN/CDC report (dated 2012). Because of the unchanged
      VAP level during the 2.5-year observation period, the root cause needs to be
      determined and action should be taken to resolve this issue.

PMID- 25751292
TI  - Continuation of pregnancy in a woman with critical brain injury.
AB  - BACKGROUND: Critical brain injury can lead to brain death, which is medically and
      legally considered the death of an individual. Further therapy is discontinued,
      unless organ donation is possible or brain death occurs in a pregnant woman. CASE
      REPORT: A 30-year old woman at 22 weeks gestation developed a subarachnoid
      haemorrhage from a ruptured cerebral artery aneurysm. The patient was admitted to
      the Intensive Care Unit in critical condition. On treatment day 3, the symptoms
      of brain death occurred. Due to possible complications, the apnoea test and
      instrumental examinations were not performed. Therapy maintaining vital functions
      was carried out in order to sustain the pregnancy. The patient was ventilated,
      received cardiac-supportive drugs, hormone replacement therapy, enteral and
      parenteral feedings and systemic infections were treated as well. At the
      beginning of the 27th week of gestation, massive bleeding from the airways
      developed. A Caesarean section was performed, and a female neonate was born,
      birth weight 680 g, the Apgar scores 4, 6 and 6 at 1st, 5th and 10th minute,
      respectively. After 3.5 months, the baby was discharged from the Neonatal
      Intensive Care Unit. Her development at the age of 8 months is normal.
      CONCLUSIONS: The case described and similar cases reported in the literature
      demonstrate that the maternal brain death is an interdisciplinary medical
      challenge. Thanks to intensive care techniques, maternal somatic functions can be
      maintained, and a healthy child can be delivered.

PMID- 25751293
TI  - Heparin-induced thrombocytopenia.
AB  - Heparin-induced thrombocytopenia (HIT) is a clinical immune-mediated syndrome;
      symptoms of HIT result from the development of arterial and venous thrombosis and
      are correlated with the severity of the thrombocytopenia. In all patients
      receiving heparin preparations in intensive care units, platelet counts should be
      monitored every 2-3 days throughout therapy, particularly during days 4-14 when
      HIT is most likely to develop. The major screening tests should always involve a
      clinical assessment of HIT probability (4Ts or HEP scoring systems) and enzymatic
      immunoassays (IgG antibodies) for patients with a moderate to high risk of HIT.
      The full possibilities of such advanced diagnostic procedures are limited in
      Poland because functional tests are still not widely available. If the diagnosis
      is questionable, all heparin preparations should be withdrawn and an alternative
      method of anticoagulation instituted until HIT has been conclusively excluded.
      The use of new-generation anticoagulants (direct thrombin or Xa factor
      inhibitors) is currently considered the treatment of choice. Old-generation
      anticoagulants should not be administered (vitamin K antagonists) as they can
      aggravate thrombosis. If administered, their action should be reversed by vitamin
      K once HIT is confirmed. Antithrombotic therapy with "new" anticoagulants should
      be carried out at least until platelet counts return to the baseline values; the
      recommended duration of therapy is 4 weeks in patients with isolated
      thrombocytopenia or 4 months in those with thrombotic complications. Vitamin K
      antagonists should not be applied until the normal platelet count is restored
      (usually > 150 G L-1). When the therapy with vitamin K antagonists is
      reintroduced, "old" antagonists should be administered simultaneously with a
      "new" anticoagulant for at least 5 days due to an initial decrease in protein C
      concentration concentration, provided that the therapeutic value of INR is
      maintained (> 2) for at least 2 days. 

PMID- 25751294
TI  - Assessment of regional ventilation in acute respiratory distress syndrome by
      electrical impedance tomography.
AB  - Mechanical ventilation in acute respiratory distress syndrome (ARDS) incurs a
      risk of ventilator-associated lung injury (VALI) from inhomogeneous conditions
      and different properties of dependent and non-dependent lung regions at risk of
      atelectasis and overdistension, respectively. Electrical impedance tomography
      (EIT) offers regional ventilation assessment to optimise treatment with
      mechanical ventilation. This article provides an overview of scientific
      literature on the application of impedance tomography in acute respiratory
      distress syndrome. It also presents the results of EIT studies in different
      clinical situations that may be of use in implementing impedance tomography for
      treating ARDS. 

PMID- 25751295
TI  - Remifentanil for labour pain relief.
AB  - Labour is thought to be one of the most intense and painful experiences in a
      woman's life. Numerous studies using a Visual Analogue Scale invariably
      demonstrate that 20% of women in labour describe the pain as "unbearable" and 60%
      describe the pain as "very intense". Since the mid-1980s, continuous epidural
      analgesia during labour has been considered the gold standard of labour
      anaesthesia and is currently the most frequently used. There are situations in
      which this type of analgesia could not be used. An alternative pain management is
      administration of parenteral opioids, the most frequently used of which is
      pethidine. Its use is associated with adverse effects and unsatisfactory
      analgesia. Since the second half of the 20th century, a new generation of
      opioids, such as fentanyl or remifentanil, has been used. Despite their much
      better pharmacokinetic and pharmacodynamic parameters, obstetricians, midwives
      and neonatologists are most aware of pethidine, probably because it has been used
      for the longest period of time, despite its disadvantages and the risk that its
      use entails. The drug that is nearest to ideal is remifentanil. The countries in
      which it is widely used as an alternative type of labour anaesthesia have
      developed practice standards or guidelines practice. Guidelines and alternatives
      to pethidine protocols for effective labour analgesia in Poland might be merited.

PMID- 25751296
TI  - Onset of sediment transport is a continuous transition driven by fluid shear and
      granular creep.
AB  - Fluid-sheared granular transport sculpts landscapes and undermines
      infrastructure, yet predicting the onset of sediment transport remains
      notoriously unreliable. For almost a century, this onset has been treated as a
      discontinuous transition at which hydrodynamic forces overcome gravity-loaded
      grain-grain friction. Using a custom laminar-shear flume to image slow granular
      dynamics deep into the bed, here we find that the onset is instead a continuous
      transition from creeping to granular flow. This transition occurs inside the
      dense granular bed at a critical viscous number, similar to granular flows and
      colloidal suspensions and inconsistent with hydrodynamic frameworks. We propose a
      new phase diagram for sediment transport, where 'bed load' is a dense granular
      flow bounded by creep below and suspension above. Creep is characteristic of
      disordered solids and reminiscent of soil diffusion on hillslopes. Results
      provide new predictions for the onset and dynamics of sediment transport that
      challenge existing models. 

PMID- 25751297
TI  - Dynamics of DNA hydroxymethylation in zebrafish.
AB  - During embryonic development in mammals, most of the methylated cytosines in the
      paternal genome are converted to 5-hydroxymethyldeoxycytidine (hmC), as part of
      DNA methylation reprogramming. Recent data also suggest tissue-specific
      functional roles of hmC, perhaps as an epigenetic mark. However, limited data are
      available on the levels and tissue distribution in zebrafish. In this study, we
      used high-performance liquid chromatography mass spectrometry to quantify hmC and
      5-methyldeoxycytidine (mC) in zebrafish during development and in different
      tissues of the adult fish. Low levels of mC were found at 0.5 hours
      postfertilization (hpf) (1-2 cell stage) (1.9%), and increased to 8.4% by 96 hpf,
      with similar levels observed in different adult tissues. No hmC was detected up
      to 12 hpf, but levels increased during development from 24 up to 96 hpf (0.23%).
      In tissues, the highest levels of hmC were found in the brain (0.49%),
      intermediate levels in muscle (0.13%), liver (0.08%), and intestine (0.06%) and
      low levels in testis (0.01%), with an inverse correlation between hmC and mC. Our
      results indicate similar tissue distribution and levels of hmC between zebrafish
      and mammals, but distinct differences during embryonic development. Although more
      research is needed, these results support the use of zebrafish as an alternative
      model in the elucidation of tissue-specific functions of hmC.

PMID- 25751298
TI  - Blastocyst metabolism.
AB  - The mammalian blastocyst exhibits an idiosyncratic metabolism, reflecting its
      unique physiology and its ability to undergo implantation. Glucose is the primary
      nutrient of the blastocyst, and is metabolised both oxidatively and through
      aerobic glycolysis. The production of significant quantities of lactate by the
      blastocyst reflects specific metabolic requirements and mitochondrial regulation;
      it is further proposed that lactate production serves to facilitate several key
      functions during implantation, including biosynthesis, endometrial tissue
      breakdown, the promotion of new blood vessel formation and induction of local
      immune-modulation of the uterine environment. Nutrient availability, oxygen
      concentration and the redox state of the blastocyst tightly regulate the relative
      activities of specific metabolic pathways. Notably, a loss of metabolic normality
      is associated with a reduction in implantation potential and subsequent fetal
      development. Even a transient metabolic stress at the blastocyst stage culminates
      in low fetal weights after transfer. Further, it is evident that there are
      differences between male and female embryos, with female embryos being
      characterised by higher glucose consumption and differences in their amino acid
      turnover, reflecting the presence of two active X-chromosomes before
      implantation, which results in differences in the proteomes between the sexes. In
      addition to the role of Hypoxia-Inducible Factors, the signalling pathways
      involved in regulating blastocyst metabolism are currently under intense
      analysis, with the roles of sirtuins, mTOR, AMP-activated protein kinase and
      specific amino acids being scrutinised. It is evident that blastocyst metabolism
      regulates more than the production of ATP; rather, it is apparent that
      metabolites and cofactors are important regulators of the epigenome, putting
      metabolism at centre stage when considering the interactions of the blastocyst
      with its environment. 

PMID- 25751299
TI  - The effects of Co3O4 on the structure and unusual magnetism of LaCoO3.
AB  - Bulk La(w)CoO(3) particles with w = 1.1, 1.0, 0.9, 0.8, and 0.7 were synthesized
      using starting materials with varying molar ratios of La(2)O(3) and Co(3)O(4).
      The resulting particles are characterized as LaCoO(3) crystals interfaced with a
      crystalline Co(3)O(4) phase. X-ray and neutron scattering data show little effect
      on the average structure and lattice parameters of the LaCoO(3) phase resulting
      from the Co(3)O(4) content, but magnetization data indicate that the amount of
      Co(3)O(4) strongly affects the ferromagnetic ordering at the interfaces below TC
      ~ 89 K. In addition to ferromagnetic long-range order, LaCoO(3) exhibits
      antiferromagnetic behavior with an unusual temperature dependence. The
      magnetization for fields 20 Oe ? H ? 5 kOe is fit to a combination of a power law
      ((T - TC)/TC)(beta) behavior representing the ferromagnetic long-range order and
      sigmoid-convoluted Curie-Weiss-like behavior representing the antiferromagnetic
      behavior. The critical exponent beta = 0.63 +/- 0.02 is consistent with 2D
      (surface) ordering. Increased Co(3)O(4) correlates well to increased
      ferromagnetism. The weakening of the antiferromagnetism below T ~ 40 K is a
      consequence of the lattice reaching a critical rhombahedral distortion as T is
      decreased for core regions far from the Co(3)O(4) interfaces. We introduce a
      model that describes the ferromagnetic behavior of the interface regions and the
      unusual antiferromagnetism of the core regions.

PMID- 25751300
TI  - Effects of Alpha-Lipoic Acid Supplementation on Inflammatory Biomarkers and
      Matrix Metalloproteinase-3 in Rheumatoid Arthritis Patients.
AB  - OBJECTIVE: Although many studies have considered alpha-lipoic acid (ALA) as a
      potent antioxidant with anti-inflammatory functions in oxidative stress
      associated inflammatory diseases, few studies have evaluated its efficacy in
      rheumatoid arthritis (RA). Therefore, we aimed to examine the effects of ALA on
      serum biomarkers of joint damage and inflammation in women with RA. METHODS: We
      performed a randomized, double-blind, placebo-controlled clinical trial in which
      RA patients (n = 70) aged 20-50 years were randomly assigned 1:1 to receive
      either ALA (1200 mg/day) or placebo for 8 weeks. Fasting blood samples were taken
      before and after the study to analyze inflammatory biomarkers including serum
      high-sensitivity C-reactive protein (hs-CRP), tumor necrosis factor-alpha (TNF
      alpha), interleukin-6 (IL-6), and serum matrix metalloproteinase-3 (MMP-3) as a
      marker of joint erosion. Moreover, 3-day dietary records, the International
      Physical Activity Questionnaire (IPAQ), and the Spielberger State-Trait anxiety
      inventory form Y (STAI-Y) were assessed before and after the intervention.
      RESULTS: Sixty-five RA patients completed the trial. No statistically significant
      differences were observed in serum levels of hs-CRP, TNF-alpha, IL-6, and MMP-3
      within and between the ALA and placebo groups (p > 0.05). There were no
      statistically significant differences in dietary intakes, physical activity, and
      anxiety levels between groups at baseline and they remained statistically
      unchanged during the study period (p > 0.05). CONCLUSION: Although in theory ALA
      supplementation could serve as a beneficial nutraceutical in RA patients, in the
      present study serum inflammatory biomarkers and MMP-3 were not significantly
      affected by 8 weeks of ALA supplementation.

PMID- 25751301
TI  - Cell type-specific expression profile and signaling requirements in early
      hematopoietic reprogramming.
AB  - Hematopoietic cells represent an attractive starting cell type for induced
      pluripotent stem (iPS) cells induction, yet the molecular mechanisms in
      hematopoietic reprogramming are poorly defined. In this study, we showed that
      long-term hematopoietic stem cells are more amenable for iPS cells induction
      among several hematopoietic stem and progenitor cell (HSPC) populations, and that
      this is accompanied by an earlier induction of the transcriptional program that
      is involved in the promotion of macromolecule metabolism and cell proliferation.
      Notably, we identified multiple signaling pathways that exhibited distinct
      expression patterns in HSPCs compared to that of fibroblasts, which is the most
      commonly used model for probing the somatic reprogramming process. We further
      experimentally confirmed the differential requirements of the Wnt/beta-catenin
      and transforming growth factor-beta (TGF-beta) signaling pathways in these two
      cell types. These data demonstrate that hematopoietic cells have a cell-type
      specific transcriptional program and possess unique signaling requirements in the
      early phase of reprogramming. 

PMID- 25751302
TI  - FLJ25439, a novel cytokinesis-associated protein, induces tetraploidization and
      maintains chromosomal stability via enhancing expression of endoplasmic reticulum
      stress chaperones.
AB  - Investigation of the mechanisms leading to aneuploidy and polyploidy is critical
      to cancer research. Previous studies have provided strong evidence of the
      importance of tetraploidization as an early step in tumorigenesis. In cancer
      cells, tetraploid cells may contribute to abnormal mitotic progression, which may
      be associated with cytokinesis failure. Tetraploidy leads to genomic instability
      due to centrosome and chromosome over-replication. Until now, the mechanism by
      which cells maintain tetraploid status has been unknown. Here, we identified a
      novel D box-containing protein, FLJ25439, which displays a dynamic expression
      profile during mitosis/cytokinesis with the midbody as the most prominent
      associated structure. To understand the function of FLJ25439, we established
      stable cell lines overexpressing FLJ25439. FLJ25439-overexpression cells grew
      slower and displayed a tetraploid DNA content in comparison with diploid parental
      cells. They also showed aberrant mitosis and dysregulated expression of p53, pRb
      and p21, suggesting a defect in cell cycle progression. To explore the molecular
      mechanisms responsible for FLJ25439-induced tetraploidization, we conducted a
      comparative analysis of the global protein expression patterns of wild type and
      overexpressors using proteomics and bioinformatics approaches. Protein category
      profiling indicated that FLJ25439 is involved in pathways related to anti
      apoptosis, protein folding, the cell cycle, and cytoskeleton regulation.
      Specifically, genotoxic-stress- and ER stress-related chaperone proteins greatly
      contributed to the FLJ25439 overexpression phenotypes. The results of this study
      pave the way to our further understanding of the role of this novel cytokinesis
      related protein in protecting cells from environmental stress and tetraploid
      formation. 

PMID- 25751303
TI  - Plateau-Rayleigh crystal growth of periodic shells on one-dimensional substrates.
AB  - The Plateau-Rayleigh instability was first proposed in the mid-1800s to describe
      how a column of water breaks apart into droplets to lower its surface tension.
      This instability was later generalized to account for the constant volume
      rearrangement of various one-dimensional liquid and solid materials. Here, we
      report a growth phenomenon that is unique to one-dimensional materials and
      exploits the underlying physics of the Plateau-Rayleigh instability. We term the
      phenomenon Plateau-Rayleigh crystal growth and demonstrate that it can be used to
      grow periodic shells on one-dimensional substrates. Specifically, we show that
      for certain conditions, depositing Si onto uniform-diameter Si cores, Ge onto Ge
      cores and Ge onto Si cores can generate diameter-modulated core-shell nanowires.
      Rational control of deposition conditions enables tuning of distinct
      morphological features, including diameter-modulation periodicity and amplitude
      and cross-sectional anisotropy. Our results suggest that surface energy
      reductions drive the formation of periodic shells, and that variation in kinetic
      terms and crystal facet energetics provide the means for tunability. 

PMID- 25751304
TI  - Breaking the depth dependency of phototherapy with Cerenkov radiation and low
      radiance-responsive nanophotosensitizers.
AB  - The combination of light and photosensitizers for phototherapeutic interventions,
      such as photodynamic therapy, has transformed medicine and biology. However, the
      shallow penetration of light into tissues and the reliance on tissue oxygenation
      to generate cytotoxic radicals have limited the method to superficial or
      endoscope-accessible lesions. Here we report a way to overcome these limitations
      by using Cerenkov radiation from radionuclides to activate an oxygen-independent
      nanophotosensitizer, titanium dioxide (TiO2). We show that the administration of
      transferrin-coated TiO2 nanoparticles and clinically used radionuclides in mice
      and colocalization in tumours results in either complete tumour remission or an
      increase in their median survival. Histological analysis of tumour sections
      showed the selective destruction of cancerous cells and high numbers of tumour
      infiltrating lymphocytes, which suggests that both free radicals and the
      activation of the immune system mediated the destruction. Our results offer a way
      to harness low-radiance-sensitive nanophotosensitizers to achieve depth
      independent Cerenkov-radiation-mediated therapy. 

PMID- 25751307
TI  - Recent advances in proteomics applied to elucidate the role of environmental
      impacts on human health and organismal function.

PMID- 25751305
TI  - An endogenous nanomineral chaperones luminal antigen and peptidoglycan to
      intestinal immune cells.
AB  - In humans and other mammals it is known that calcium and phosphate ions are
      secreted from the distal small intestine into the lumen. However, why this
      secretion occurs is unclear. Here, we show that the process leads to the
      formation of amorphous magnesium-substituted calcium phosphate nanoparticles that
      trap soluble macromolecules, such as bacterial peptidoglycan and orally fed
      protein antigens, in the lumen and transport them to immune cells of the
      intestinal tissue. The macromolecule-containing nanoparticles utilize epithelial
      M cells to enter Peyer's patches, small areas of the intestine concentrated with
      particle-scavenging immune cells. In wild-type mice, intestinal immune cells
      containing these naturally formed nanoparticles expressed the immune tolerance
      associated molecule 'programmed death-ligand 1', whereas in NOD1/2 double
      knockout mice, which cannot recognize peptidoglycan, programmed death-ligand 1
      was undetected. Our results explain a role for constitutively formed calcium
      phosphate nanoparticles in the gut lumen and show how this helps to shape
      intestinal immune homeostasis. 

PMID- 25751306
TI  - Analysis of pineapple mealybug wilt associated virus -1 and -2 for potential RNA
      silencing suppressors and pathogenicity factors.
AB  - Higher plants use RNA silencing to defend against viral infections. As a counter
      defense, plant viruses have evolved proteins that suppress RNA silencing.
      Mealybug wilt of pineapple (MWP), an important disease of pineapple, has been
      associated with at least three distinct viruses, Pineapple mealybug wilt
      associated virus -1, -2, and -3 (PMWaV-1, -2, and -3). Selected open reading
      frames (ORFs) of PMWaV-1 and PMWaV-2 were screened for their local and systemic
      suppressor activities in Agrobacterium-mediated transient assays using green
      fluorescent protein (GFP) in Nicotiana benthamiana. Results indicate that PMWaV-2
      utilizes a multiple-component RNA silencing suppression mechanism. Two proteins,
      p20 and CP, target both local and systemic silencing in N. benthamiana, while the
      p22 and CPd proteins target only systemic silencing. In the related virus PMWaV
      1, we found that only one of the encoded proteins, p61, had only systemic
      suppressor activity. Of all the proteins tested from both viruses, only the PMWaV
      2 p20 protein suppressed local silencing induced by double-stranded RNA (dsRNA),
      but only when low levels of inducing dsRNA were used. None of the proteins
      analyzed could interfere with the short distance spread of silencing. We examined
      the mechanism of systemic suppression activity by investigating the effect of
      PMWaV-2-encoded p20 and CP proteins on secondary siRNAs. Our results suggest that
      the PMWaV-2 p20 and CP proteins block the systemic silencing signal by repressing
      production of secondary siRNAs. We also demonstrate that the PMWaV-2 p20 and p22
      proteins enhanced the pathogenicity of Potato virus X in N. benthamiana.

PMID- 25751308
TI  - Structure of CPV17 polyhedrin determined by the improved analysis of serial
      femtosecond crystallographic data.
AB  - The X-ray free-electron laser (XFEL) allows the analysis of small weakly
      diffracting protein crystals, but has required very many crystals to obtain good
      data. Here we use an XFEL to determine the room temperature atomic structure for
      the smallest cytoplasmic polyhedrosis virus polyhedra yet characterized, which we
      failed to solve at a synchrotron. These protein microcrystals, roughly a micron
      across, accrue within infected cells. We use a new physical model for XFEL
      diffraction, which better estimates the experimental signal, delivering a high
      resolution XFEL structure (1.75 A), using fewer crystals than previously required
      for this resolution. The crystal lattice and protein core are conserved compared
      with a polyhedrin with less than 10% sequence identity. We explain how the
      conserved biological phenotype, the crystal lattice, is maintained in the face of
      extreme environmental challenge and massive evolutionary divergence. Our improved
      methods should open up more challenging biological samples to XFEL analysis. 

PMID- 25751309
TI  - Role of ethrel in causation of floral malformation in mango cv. Amrapali: a
      scanning electron microscopy study.
AB  - Floral malformation is a main constraint to reduce fruit yield in mango plants.
      Recently, we report on the role of putrescine in normalizing the functional
      morphology of mango flower by reducing various adverse effects of ethylene. Here,
      ethrel, an ethylene releasing compound, was exogenously applied to mango plant cv
      Amrapali to evaluate the response of flower development under high level of
      ethylene. Scanning electron microscopy (SEM) study showed that ethrel treated
      flowers were observed to progressively be deformed and remain unbloom. The flower
      buds were not distinguishable and flower parts such as petals, sepals, anther and
      stigma were not properly developed. The stamen showed fused anther lobes and
      carpel depicted curved style with pointed stigma. The findings of present study
      suggest the involvement of ethylene to abort the functional morphology of flower
      and thereby development of malformation. 

PMID- 25751310
TI  - Achieving health equity by design.

PMID- 25751311
TI  - Training in Hepatopancreatobiliary Surgery: Assessment of the
      Hepatopancreatobiliary Surgery Workforce in North America.
AB  - OBJECTIVE: Evaluate the current status of Hepatopancreatobiliary (HPB) Surgery
      workforce in North America. BACKGROUND: HPB fellowships have proliferated, with
      HPB surgeons entering the field through 3 pathways: transplant surgery, surgical
      oncology, or HPB surgery training. Impact of this growth is unknown. METHODS: An
      anonymous survey was distributed to 654 is used as HPB surgeons from October 2012
      to January 2013. Questions evaluated satisfaction with job availability after
      training and description of current practice. Nationwide Inpatient Sample (NIS)
      data from 2003 to 2010 was queried to describe the growth of HPB cases in the
      United States; these data were compared to prior HPB workforce projections
      performed using 2003 NIS data. RESULTS: A total of 416 HPB surgeons responded
      (66%). HPB surgeons are concentrated in a small number of states/provinces with a
      lack of HPB surgeon workforce in central United States. HPB graduates from 2008
      to 2012 report increased difficulty in identifying an HPB-focused practice versus
      prior to 2008. Mature HPB surgery practices report a composition of 25% to 50%
      non-HPB operative cases. Fifty-one percent of respondents reported an opinion
      that current HPB Surgeon production was excessive; however, 2010 NIS data
      demonstrate that major HPB surgery cases have grown significantly more than was
      previously projected using 2003 NIS data. CONCLUSIONS AND RELEVANCE: A cohesive
      strategy for responsibly responding to the HPB surgical workforce requirements of
      North America is needed. Elevation of training standards, standardization of
      requirements for certification, and careful modeling that accounts for
      regionalization of care should be pursued to prevent overtraining and
      decentralization of HPB surgical care in the future.

PMID- 25751312
TI  - Anti-incretin, Anti-proliferative Action of Dopamine on beta-Cells.
AB  - Human islet beta-cells exploit an autocrine dopamine (DA)-mediated inhibitory
      circuit to regulate insulin secretion. beta-Cells also express the DA active
      transporter and the large neutral amino acid transporter heterodimer enabling
      them to import circulating DA or its biosynthetic precursor, L-3,4
      dihydroxyphenylalanine (L-DOPA). The capacity to import DA or L-DOPA from the
      extracellular space possibly indicates that DA may be an endocrine signal as
      well. In humans, a mixed meal stimulus is accompanied by contemporary serum
      excursions of incretins, DA and L-DOPA, suggesting that DA may act as an anti
      incretin as postulated by the foregut hypothesis proposed to explain the early
      effects of bariatric surgery on type 2 diabetes. In this report, we take a
      translational step backwards and characterize the kinetics of plasma DA and
      incretin production after a mixed meal challenge in a rat model and study the
      integration of incretin and DA signaling at the biochemical level in a rodent
      beta-cell line and islets. We found that there are similar excursions of
      incretins and DA in rats, as those reported in humans, after a mixed meal
      challenge and that DA counters incretin enhanced glucose-stimulated insulin
      secretion and intracellular signaling at multiple points from dampening calcium
      fluxes to inhibiting proliferation as well as apoptosis. Our data suggest that DA
      is an important regulator of insulin secretion and may represent 1 axis of a gut
      level circuit of glucose and beta-cell mass homeostasis. 

PMID- 25751313
TI  - Contribution of Intronic miR-338-3p and Its Hosting Gene AATK to Compensatory
      beta-Cell Mass Expansion.
AB  - The elucidation of the mechanisms directing beta-cell mass regeneration and
      maintenance is of interest, because the deficit of beta-cell mass contributes to
      diabetes onset and progression. We previously found that the level of the
      microRNA (miRNA) miR-338-3p is decreased in pancreatic islets from rodent models
      displaying insulin resistance and compensatory beta-cell mass expansion,
      including pregnant rats, diet-induced obese mice, and db/db mice. Transfection of
      rat islet cells with oligonucleotides that specifically block miR-338-3p activity
      increased the fraction of proliferating beta-cells in vitro and promoted survival
      under proapoptotic conditions without affecting the capacity of beta-cells to
      release insulin in response to glucose. Here, we evaluated the role of miR-338-3p
      in vivo by injecting mice with an adeno-associated viral vector permitting
      specific sequestration of this miRNA in beta-cells. We found that the adeno
      associated viral construct increased the fraction of proliferating beta-cells
      confirming the data obtained in vitro. miR-338-3p is generated from an intron of
      the gene coding for apoptosis-associated tyrosine kinase (AATK). Similarly to miR
      338-3p, we found that AATK is down-regulated in rat and human islets and
      INS832/13 beta-cells in the presence of the cAMP-raising agents exendin-4,
      estradiol, and a G-protein-coupled Receptor 30 agonist. Moreover, AATK expression
      is reduced in islets of insulin resistant animal models and selective silencing
      of AATK in INS832/13 cells by RNA interference promoted beta-cell proliferation.
      The results point to a coordinated reduction of miR-338-3p and AATK under insulin
      resistance conditions and provide evidence for a cooperative action of the miRNA
      and its hosting gene in compensatory beta-cell mass expansion. 

PMID- 25751315
TI  - How health managers can use data mining for predicting individuals' risks of
      contracting nosocomial pneumonia.
AB  - This article explains how managers can use a new data-mining technique for
      solving problems related to individual risks of contracting nosocomial pneumonia.
      Using the genetic algorithm, a search technique provides practitioners with an
      optimal choice of parameters for Gini boosting type decision tree models. Thus,
      managers and technicians can choose better models. These new parameters are
      genetically controlled: number of trees, depth of trees, trimming factor, cross
      validation (to avoid overfitting), proportion of the population used, and the
      minimum size to split a node. This technique has been satisfactorily tested on
      health data. 

PMID- 25751316
TI  - The behavioral consequences of service quality: an empirical study in the Chinese
      retail pharmacy industry.
AB  - This study focuses on the impacts of service quality and examines the mediating
      effects of customer satisfaction and customer loyalty on willingness to pay more.
      The authors collected survey data from 479 actual retail pharmacy customers in
      China and used the structural equation modeling approach to test the hypotheses.
      The results reveal six dimensions of service quality and the differential impact
      of these dimensions on customer satisfaction and behavioral intentions. This
      study contributes to the existing literature by exploring the dimensionality of
      the service quality construct and mediating effects of customer satisfaction and
      customer loyalty in a non-Western setting. 

PMID- 25751317
TI  - The role of affect in consumer evaluation of health care services.
AB  - Health care services are typically consumed out of necessity, typically to
      recover from illness. While the consumption of health care services can be
      emotional given that consumers experience fear, hope, relief, and joy,
      surprisingly, there is little research on the role of consumer affect in health
      care consumption. We propose that consumer affect is a heuristic cue that drives
      evaluation of health care services. Drawing from cognitive appraisal theory and
      affect-as-information theory, this article tests a research model (N = 492) that
      investigates consumer affect resulting from service performance on subsequent
      service outcomes. 

PMID- 25751318
TI  - Regulatory fit effects on children's responses to healthy eating promotion: an
      experiment testing message and celebrity fit.
AB  - This study adopts the regulatory fit theory and examines the effects of the
      celebrity and message fit on children's responses to the promotion of healthy
      eating. A 2 * 2 experiment was conducted with 87 Hong Kong children ages 11 to
      16. The results showed that a regulatory fit between the celebrity focus and the
      message focus yielded a better affective response. Specifically, children found a
      poster ad more convincing, liked it more, held more positive feelings, and found
      the poster ad more interesting in the fit conditions. Implications and future
      research directions were discussed. 

PMID- 25751314
TI  - Minireview: neural signaling of estradiol in the hypothalamus.

PMID- 25751319
TI  - Merging public relations with health communication in the context of university
      alcohol prevention.
AB  - The scope of this study is to determine whether social norms marketing should be
      further evaluated according to its ability to serve as a public relations tactic
      for universities. Based on a framework of social norms theory and strategic
      issues management, this study uses a web-based survey with university parents (N
      = 173) to identify relationships among exaggerated parental misperceptions of
      student binge drinking, parental awareness of alcohol prevention programs, and
      parental perceptions of organizational legitimacy. Findings from this study are
      used to make the argument that health communication and public relations should
      be viewed as interrelated concepts in the context of university alcohol
      prevention. 

PMID- 25751320
TI  - The effect of altruism on the spending behavior of elderly caregivers of family
      members with HIV/AIDS in South African townships.
AB  - HIV/AIDS has led to an enormous demand for health care in the developing world
      and many governments have opted to capitalize on altruistic home-based
      caregivers. These caregivers are mainly poor older women and their financial
      survival is critically important to themselves and their families. We found that
      as the patient's illness progressed: (a) the altruistic cultural norm "ubuntu"
      led the caregiver to increase spending and (b) the social pressure (sanction) of
      stigma led to a very dramatic drop in direct interpersonal assistance. The impact
      on their spending, health care, and the related public policies are discussed. 

PMID- 25751321
TI  - Health care information seeking and seniors: determinants of Internet use.
AB  - While seniors are the most likely population segment to have chronic diseases,
      they are the least likely to seek information about health and diseases on the
      Internet. An understanding of factors that impact seniors' usage of the Internet
      for health care information may provide them with tools needed to improve health.
      This research examined some of these factors as identified in the comprehensive
      model of information seeking to find that demographics, trust in health
      information websites, perceived usefulness of the Internet, and internal locus of
      control each significantly impact seniors' use of the Internet to seek health
      information. 

PMID- 25751324
TI  - Identification of Unique, Heterozygous Germline Mutation, STK11 (p.F354L), in a
      Child with an Encapsulated Follicular Variant of Papillary Thyroid Carcinoma
      within Six Months of Completing Treatment for Neuroblastoma.
AB  - Papillary thyroid carcinoma (PTC) is rare in children, although it is a known
      secondary malignancy after treatment for neuroblastoma (NB). The interval between
      NB treatment completion and PTC is usually more than 5 years. A 4-year-old,
      female patient with a high risk adrenal NB was found to have a 2.9-cm, right
      thyroid nodule on surveillance chest computed tomography (CT) 6 months after
      completion of her NB treatment (induction chemotherapy, tumor resection,
      autologous stem cell transplantation, external beam radiation to the abdominal
      tumor site, immunotherapy, and retinoic acid). Posttreatment surveillance
      included iodine-123-metaiodobenzylguanidine scans and CT scans. Fine-needle
      aspiration of the thyroid nodule diagnosed a follicular neoplasm, which was
      negative for BRAF, NRAS, KRAS, HRAS, PAX8/PPARg, and RET/PTC mutations, without
      evidence of metastatic NB. Nodule histology demonstrated an encapsulated
      follicular variant of PTC (FVPTC). Next-generation sequence analysis for a 46
      cancer-gene profile was performed on both tumors with subsequent peripheral blood
      DNA testing. A heterozygous missense mutation in STK11 (F354L) was identified in
      both the NB and FVPTC. This mutation was also detected in peripheral blood
      mononuclear cells. Two additional heterozygous somatic missense mutations of
      uncertain significance were identified: KDR/VEGF receptor 2 (Q472H) on chromosome
      4 and MET (N375S) on chromosome 7. To our knowledge, this is the shortest
      reported duration from completion of NB treatment to detection of thyroid cancer.
      The association of the STK11 gene with Peutz-Jeghers syndrome, lung
      adenocarcinomas, and medullary thyroid cancer leads to a possible association
      between this genetic variant and our patient's tumors. 

PMID- 25751325
TI  - IJDVL International Awards.

PMID- 25751326
TI  - Designing a research protocol in clinical dermatology: common errors and how to
      avoid them.

PMID- 25751327
TI  - Phototherapy for mycosis fungoides.
AB  - BACKGROUND: Both phototherapy and photochemotherapy have been used in all stages
      of mycosis fungoides since they improve the symptoms and have a favourable
      adverse effect profile. MATERIALS AND METHODS: We performed an extensive search
      of published literature using keywords like "phototherapy", "photochemotherapy",
      "NBUVB", "PUVA", "UVA1", "mycosis fungoides", and "Sezary syndrome", and included
      systematic reviews, meta-analysis, national guidelines, randomized controlled
      trials (RCTs), prospective open label studies, and retrospective case series.
      These were then arranged according to their levels of evidence. RESULTS: Five
      hundred and forty three studies were evaluated, of which 107 fulfilled the
      criteria for inclusion in the guidelines. CONCLUSIONS AND RECOMMENDATIONS:
      Photochemotherapy in the form of psoralens with ultraviolet A (PUVA) is a safe,
      effective, and well tolerated first line therapy for the management of early
      stage mycosis fungoides (MF), that is, stage IA, IB, and IIA (Level of evidence
      1+, Grade of recommendation B). The evidence for phototherapy in the form of
      narrow-band UVB (NB-UVB) is less robust (Level of evidence 2++, Grade of
      recommendation B) but may be considered at least as effective as PUVA in the
      treatment of early-stage MF as an initial therapy. In patients with patches and
      thin plaques, NB-UVB should be preferentially used. PUVA may be reserved for
      patients with thick plaques and those who relapse after initial NB-UVB therapy.
      For inducing remission, three treatment sessions per week of PUVA phototherapy or
      three sessions per week of NB-UVB phototherapy may be advised till the patient
      achieves complete remission. In cases of relapse, patients may be started again
      on PUVA monotherapy or PUVA may be combined with adjuvants like methotrexate and
      interferon (Level of evidence 2+, Grade of recommendation B). Patients with early
      stage MF show good response to combination treatments like PUVA with
      methotrexate, bexarotene or interferon-alpha-2b. However, whether these
      combinations hold a significant advantage over monotherapy is inconclusive. For
      late stage MF, the above-mentioned combination therapy may be used as first-line
      treatment (Level of evidence 3, Grade of recommendation C). Currently, there is
      no consensus regarding maintenance therapy with phototherapy once remission is
      achieved. Maintenance therapy should not be employed for PUVA routinely and may
      be reserved for patients who experience an early relapse after an initial course
      of phototherapy (Level of evidence 2+, Grade of recommendation B). Bath-water
      PUVA may be tried as an alternative to oral PUVA in case the latter cannot be
      administered as the former may show similar efficacy (Level of evidence 2-, Grade
      of recommendation C). In pediatric MF and in hypopigmented MF, both NB-UVB and
      PUVA may be tried (Level of evidence 3, Grade of recommendation D).

PMID- 25751328
TI  - Patient-assisted teledermatology practice: what is it? When, where, and how it is
      applied?
AB  - Recent teledermatology practice has been focused on different models made
      possible by robust advances in information technology leading to consistent
      interaction between the patient and health care professionals. Patient-assisted
      teledermatology practice also called patient-enabled teledermatology or home
      based teledermatology is one such novel model. There is a lack of scientific
      literature and substantive reviews on patient-assisted teledermatology practice.
      The present article reviews several studies and surveys on patient-assisted
      teledermatology practice and outlines its advantages and barriers to clinical
      utility and analyses the potentiality of this concept. Incorporating patient
      assisted teledermatology practice as a novel model in the revised classification
      of teledermatology practice is proposed. In patient-assisted teledermatology, the
      patient can upload his/her clinical images as a first contact with the
      dermatologist or an initial face-to-face examination can be followed by
      teledermatology consultations. The latter method is well suited to chronic
      diseases such as psoriasis, vitiligo, and leg ulcers, which may need frequent
      follow-up entailing significant costs and time, particularly in the elderly.
      Teledermatology may also be used by the treating dermatologist to seek expert
      opinion for difficult cases. Studies have demonstrated the importance and
      usability of the concept of patient-assisted teledermatology practice. Various
      teledermatology care models are available and the appropriate model should be
      chosen depending on whether the clinical situation is that of easily diagnosed
      cases ("spotters"), chronic cases or doubtful cases and difficult-to-manage
      cases. 

PMID- 25751329
TI  - Relapse in psoriasis with two different tapering regimens of methotrexate: a
      randomized open-label controlled study.
AB  - Background : Systemic therapy with methotrexate is a very useful modality in
      psoriasis, but relapses can occur soon after stopping it. Aim : To compare the
      relapse rates in psoriasis with two different tapering regimens of methotrexate
      after control is achieved. Methods : This was a randomized open-label controlled
      study, and patients of chronic plaque psoriasis with psoriasis area and severity
      index (PASI) >10 were included. Methotrexate 0.3 mg/kg weekly was given and the
      PASI calculated every 2 weeks. After achieving a 75% reduction in the PASI (PASI
      75), patients were assigned randomly in to one of three groups. In the half-dose
      group, the dose of methotrexate was reduced to half and given weekly; in the 2
      weekly group, the same dose was given at 2-week intervals; in the control group,
      methotrexate was stopped. Patients were followed up for 12 weeks. Results : Out
      of 141 registered patients, 81 were included: 27 in the half-dose group, 28 in
      the 2-weekly group, and 26 in the control group. After further exclusions due to
      adverse effects and loss to follow-up, the results were analysed for 16, 17 and
      19 patients respectively in the 3 groups. There was statistically a highly
      significant difference in relapse rates between the half-dose and control groups
      (P < 0.001), and a significant difference between the 2-weekly and control groups
      (P = 0.001). Relapse rates in the half-dose and 2-weekly groups did not show a
      significant difference (P = 0.680). LIMITATION: Many (35.8%) patients were
      excluded and only 52 (64.2%) completed the study. CONCLUSION: There appears to be
      no significant difference in the frequency of relapse in psoriasis whether
      methotrexate is tapered by halving the weekly dose or by doubling the interval
      between two doses, and both methods led to fewer relapses than abrupt cessation
      of the drug.

PMID- 25751330
TI  - Screening for depressive disorders in outpatients with mild to moderate
      psoriasis: a study from North India.
AB  - BACKGROUND: Psoriasis and depressive disorders commonly occur together.
      Depressive disorders have an impact on the quality of life and the outcome of
      psoriasis. AIMS: The aim of this study was to test the feasibility of using a
      modification of the Hindi translation of the Patient Health Questionnaire-9 (PHQ
      9) as a verbal, clinician administered, short screening questionnaire for
      detecting depressive disorders. MATERIALS AND METHODS: One hundred and four out
      patients with psoriasis were recruited in the study. In the first stage of the
      study, socio-demographic data, Psoriasis Area Severity Index (PASI) score, and
      Dermatological Quality of Life (DLQI) score were recorded. The modified
      questionnaire was administered by the dermatologist. In the second stage,
      psychiatric diagnoses were confirmed using the Mini International
      Neuropsychiatric Interview. RESULTS: The prevalence of depressive disorders was
      39.4%. Receiver operating curve (ROC) analysis showed that the questionnaire had
      a good discriminant ability in detecting depressive disorders (area under curve:
      0.81, SE = 0.04, 95% confidence interval = 0.72-0.89). LIMITATIONS: The sample
      size is small and more studies are needed with the screening questions in
      different languages to validate the findings of the study. CONCLUSION: The
      questionnaire can be a useful screening instrument for detecting depressive
      disorders in patients with psoriasis.

PMID- 25751331
TI  - Topical photodynamic therapy in the treatment of basal cell carcinoma in
      Singaporean Chinese patients.
AB  - BACKGROUND: Topical photodynamic therapy has been used for the treatment of
      superficial and nodular basal cell carcinomas, with varying cure rates. AIMS:
      This study aims to evaluate the effectiveness of topical photodynamic therapy in
      the treatment of superficial and nodular basal cell carcinomas in Asian patients
      treated at the National Skin Centre, Singapore. MATERIALS AND METHODS: A
      retrospective analysis of Asian patients with histologically confirmed basal cell
      carcinomas and treated with photodynamic therapy was performed. RESULTS: Eight
      Chinese patients, with an equal gender distribution and mean age of 83.4 years
      were included. Five of eight basal cell carcinomas were superficial while the
      remaining three were nodular. The basal cell carcinomas were located in the head
      and neck in seven patients. The overall clearance rate at 3 months was 87.5%
      while the clearance rate for superficial and nodular basal cell carcinomas was
      100% and 66.6% respectively at 3 months. At 12 months, the overall clearance rate
      was 85. 7%. LIMITATIONS: This is a retrospective analysis with small patient
      numbers. CONCLUSIONS: In this small series of eight Asian patients, topical
      photodynamic therapy has been shown to be effective and generally well-tolerated
      in the treatment of basal cell carcinomas, particularly of the superficial
      subtype. However, larger studies are needed to evaluate its overall efficacy in
      Asian patients.

PMID- 25751332
TI  - Report of rpoB mutation in clinically suspected cases of drug resistant leprosy:
      a study from Eastern India.
AB  - BACKGROUND: The current strategy for leprosy control depends mainly on early case
      detection and providing the recommended multidrug therapy (MDT) dosage.
      Understanding the molecular mechanisms of drug resistance to each of these drugs
      is essential in providing effective treatment and preventing the spread of
      resistant strains in the community. The progress of molecular biology research
      provides a very efficient opportunity for the diagnosis of drug resistance by in
      vitro method. AIM: We aimed to investigate the point mutations within the rpoB
      gene region of the Mycobacterium leprae genome, which are responsible for
      resistance to rifampicin, in order to determine the emergence of drug resistance
      in leprosy in the Kolkata region of West Bengal. METHODS: A total of 50 patients
      with a relapse of leprosy were enrolled in the study. Skin smears were obtained
      for estimation of bacillary index and biopsies were obtained in 70% alcohol for
      extraction of DNA. The extracted DNA was amplified by M. leprae-polymerase chain
      reaction (PCR) targeting rpoB gene region. Every single nucleotide base in the
      sequence is aligned to reference sequence and identity gaps were determined by
      NCBI - BLAST. Later in-silico analysis was done to identify the changes in the
      translated protein sequences. RESULTS: A mutation at the base pair position
      2275405 where G is replaced by C in the M. leprae genome, which corresponds to
      the coding region of rpoB gene (279 bp - 2275228 to2275506), was observed in two
      patients. This missense mutation in CAC codon brings about a glutamic acid to
      histidine change in the amino acid sequence of RNA polymerase beta subunit at the
      position 442 (Glu442His), a region specific for rifampicin interaction, which
      might be responsible for unresponsiveness to rifampicin by manifesting a stable
      bacteriological index in these 2 patients even after completion of 24 months of
      multibacillary multi-drug therapy (MB-MDT). LIMITATIONS: The major limitations of
      multiple-primer PCR amplification refractory mutation system (MARS) assay is that
      it capable of detecting mutation at codon 425 and cannot distinguish any silent
      amino acid changes. CONCLUSION: The study indicates the existence of rifampicin
      drug resistance in Eastern India.

PMID- 25751333
TI  - Frontal fibrosing alopecia and lichen planopilaris in HLA-identical mother and
      daughter.
AB  - Frontal fibrosing alopecia (FFA) is a lymphocyte-mediated scarring alopecia
      thought to be a variant of lichen planopilaris (LPP). We present a 67-year-old
      woman with frontal fibrosing alopecia whose daughter was diagnosed to have lichen
      planopilaris. Both patients had identical human leukocyte antigen (HLA) D types,
      supporting a phenotypical relationship between the two clinical entities.
      Interestingly, our patient also had of autoimmune chronic atrophic gastritis, a
      previously unreported association. 

PMID- 25751334
TI  - Psoriasis in autoimmune polyendocrine syndrome type I: a possible complication or
      a non-endocrine minor component?
AB  - INTRODUCTION: Autoimmune polyendocrine syndrome type I (APS I) is an autosomal
      recessive systemic autoimmune disorder, affecting primarily endocrine glands, in
      which chronic mucocutaneous candidiasis is an early and prominent manifestation.
      We describe the rare occurrence of unstable psoriasis (with onset of pustular
      lesions) in a case of APS I without mucocutaneous candidiasis. A patient
      presenting with unstable psoriasis (with onset of pustular lesions) was detected
      to have persistent hypocalcemia which led to the diagnosis of hypoparathyroidism.
      Subsequently he was found to have hypergonadotrophic hypogonadism, primary
      adrenal insufficiency (compensated), and coeliac disease, thus confirming the
      diagnosis of APS I. Psoriasis is very rarely reported in APS I, possibly due to
      the protective effect of antibodies to Th17 cytokines, which are responsible for
      the occurrence of candidiasis in this syndrome. However, psoriasis could occur in
      APS I patients without mucocutaneous candidiasis, who lack these antibodies. In
      our patient, possible factors aggravating psoriasis include hypocalcemia due to
      hypoparathyroidism as well as coeliac disease via anti-tissue transglutaminase
      antibodies. However, defining psoriasis as a possible minor component of APS I
      would require further studies of the autoimmune regulator (AIRE) gene functions.

PMID- 25751335
TI  - Spontaneous regression in an ulcerated CK7 positive Merkel cell carcinoma.
AB  - Merkel cell carcinoma is an aggressive and frequently lethal tumor of the
      elderly, associated with sun exposure and immunosuppression which is less common
      in the dark-skinned. We report the case of a 40-year-old woman who presented with
      multiple slowly progressive, mildly itchy ulcerated plaques of size ranging from
      2 * 3 cm to 5 * 7 cm on the left knee of 1 year duration. Skin biopsy showed
      diffuse dermal infiltration by small round cells with molding of cells and
      lymphocyte infiltration. The cells stained positive for cytokeratin (CK) 20, CK7,
      neuron-specific enolase, and chromogranin. The skin lesions underwent spontaneous
      regression within 1 month of skin biopsy and have not recurred during the past 2
      years. The immune mechanisms triggered by biopsy possibly explain the spontaneous
      regression. 

PMID- 25751336
TI  - Hemorrhagic acne in immune thrombocytopenia.

PMID- 25751337
TI  - Skin substitutes in dermatology.

PMID- 25751338
TI  - Syphilis among sexually transmitted infections clinic attendees in a tertiary
      care institution: a retrospective data analysis.

PMID- 25751339
TI  - Author's reply: significance of seropositivity for syphilis in asymptomatic
      individuals.

PMID- 25751340
TI  - The pH of skin cleansers for acne.

PMID- 25751341
TI  - A curious case of hourly attacks of disabling episodic spontaneous hypothermia
      with hyperhidrosis.

PMID- 25751342
TI  - Unilateral pruritus following stroke.

PMID- 25751343
TI  - Severe abdominal wall defect leading to dehiscence in focal dermal hypoplasia
      (Goltz syndrome).

PMID- 25751344
TI  - Rothmund - Thomson syndrome with bronchiectasis: an uncommon phenotype?

PMID- 25751345
TI  - A recurrent R936X mutation of CYLD gene in a Chinese family with multiple
      familial trichoepithelioma.

PMID- 25751346
TI  - Annular epidermolytic ichthyosis: a rare phenotypic variant of bullous congenital
      ichthyosiform erythroderma.

PMID- 25751347
TI  - Precocious puberty in a 3-year-old child with systematized verrucous epidermal
      nevus.

PMID- 25751349
TI  - Churg-Strauss syndrome with asymptomatic pulmonary emboli.

PMID- 25751348
TI  - Eruptive blue nevi.

PMID- 25751350
TI  - Sweet's syndrome associated with chronic neutrophilic leukemia.

PMID- 25751351
TI  - Squamous cell carcinoma mimicking lupus vulgaris.

PMID- 25751352
TI  - Systemic anaplastic large cell lymphoma with secondary cutaneous involvement.

PMID- 25751353
TI  - Metastatic porocarcinoma.

PMID- 25751354
TI  - Papular mucinosis associated with monoclonal gammopathy of unknown significance.

PMID- 25751355
TI  - Recalling the recall phenomenon.

PMID- 25751356
TI  - Nilotinib-induced psoriasis in a patient of chronic myeloid leukemia responding
      to methotrexate.

PMID- 25751357
TI  - Aminolevulinic acid photodynamic therapy for bowenoid papulosis.

PMID- 25751358
TI  - An asymptomatic swelling on the neck.

PMID- 25751359
TI  - Association of type 2 lepra reaction with filariasis and malaria.

PMID- 25751360
TI  - Ulceronodular syphilis as the first manifestation of HIV infection.

PMID- 25751361
TI  - Black dot tinea capitis caused by trichophyton rubrum in an adult female
      presenting with cicatricial alopecia.

PMID- 25751362
TI  - White fibrous papulosis of the neck.

PMID- 25751363
TI  - Evaluation of blood and urinary mercury in pemphigus vulgaris and pemphigus
      foliaceus patients and its comparison with control group.

PMID- 25751364
TI  - Revealing the hidden health costs embodied in Chinese exports.
AB  - China emits a considerable amount of air pollutants when producing goods for
      export. Previous efforts have emphasized the magnitude of export-related
      emissions; however, their health consequences on the Chinese population have not
      been quantified. Here, we present an interdisciplinary study to estimate the
      health impact of export-related air pollution. The results show that export
      related emissions elevated the annual mean population weighted PM2.5 by 8.3
      MUg/m(3) (15% of the total) in 2007, causing 157,000 deaths and accounting for
      12% of the total mortality attributable to PM2.5-related air pollution. Compared
      to the eastern coastal provinces, the inner regions experience much larger export
      related health losses relative to their economic production gains, owing to huge
      inter-regional disparities in export structures and technology levels. A shift
      away from emission-intensive production structure and export patterns, especially
      in inner regions, could significantly help improve national exports while
      alleviating the inter-regional cost-benefit inequality. Our results provide the
      first quantification of health consequences from air pollution related to Chinese
      exports. The proposed policy recommendations, based on health burden, economic
      production gains, and emission analysis, would be helpful to develop more
      sustainable and effective national and regional export strategies. 

PMID- 25751365
TI  - Viscoelastic characterization of the primate finger pad in vivo by microstep
      indentation and three-dimensional finite element models for tactile sensation
      studies.
AB  - When we touch an object, surface loads imposed on the skin are transmitted to
      thousands of specialized nerve endings (mechanoreceptors) embedded within the
      skin. These mechanoreceptors transduce the mechanical signals imposed on them
      into a neural code of the incident stimuli, enabling us to feel the object. To
      understand the mechanisms of tactile sensation, it is critical to understand the
      relationship between the applied surface loads, mechanical state at the
      mechanoreceptor locations, and transduced neural codes. In this paper, we
      characterize the bulk viscoelastic properties of the primate finger pad and show
      its relationship to the dynamic firing rate of SA-1 mechanoreceptors. Two three
      dimensional (3D) finite element viscoelastic models, a homogeneous and a
      multilayer model, of the primate fingertip are developed and calibrated with data
      from a series of force responses to micro-indentation experiments on primate
      finger pads. We test these models for validation by simulating indentation with a
      line load and comparing surface deflection with data in the literature
      (Srinivasan, 1989, "Surface Deflection of Primate Fingertip Under Line Load," J.
      Biomech., 22(4), pp. 343-349). We show that a multilayer model with an elastic
      epidermis and viscoelastic core predicts both the spatial and temporal
      biomechanical response of the primate finger pad. Finally, to show the utility of
      the model, ramp and hold indentation with a flat plate is simulated. The
      multilayer model predicts the strain energy density at a mechanoreceptor location
      would decay at the same rate as the average dynamic firing rate of SA-1
      mechanoreceptors in response to flat plate indentation (previously observed by
      Srinivasan and LaMotte, 1991 "Encoding of Shape in the Responses of Cutaneous
      Mechanoreceptors," Information Processing in the Somatosensory System (Wenner
      Gren International Symposium Series), O. Franzen and J. Westman, eds., Macmillan
      Press, London, UK), suggesting that the rate of adaptation of SA-1
      mechanoreceptors is governed by the viscoelastic nature of its surrounding
      tissue. 

PMID- 25751366
TI  - Conception and Associated Evaluation of a Problem-Solving Training (PST) for
      Patients in the Hospital Context of Hematopoietic Stem Cell Transplantation
      (HSCT).
AB  - It appears from empirical studies that the problem-solving ability of patients is
      associated with the experience of distress and the patients' mental state. The
      goals of this study were the (1) conception and (2) associated evaluation of the
      psychological short-time intervention "problem-solving training" (PST) for
      patients hospitalized for hematopoietic stem cell transplantation (HSCT). (1) The
      conception of the PST comprised a multi-stage development phase. An existing
      manual for outpatients diagnosed with cancer was adapted to the specific
      situation of a HSCT. This was followed by development of a manual, definition of
      the general framework, instruction of coaches, and implementation in a hospital
      setting. (2) The associated evaluation of PST was conducted from the patients'
      and the coaches' point of view. A total of 22 patients and five coaches evaluated
      the training. The training was evaluated by both patients and coaches as being
      well achievable with the exception of a limited time frame for the first module.
      The manual explanations were judged to be intelligible by all participants.
      Regarding on-topic alertness, patients were, on average, rated as "rather "to
      "very attentive." The patients evaluated the response to their needs as "good."
      They further assessed their overall condition due to the training as "good." This
      study provides preliminary evidence for the feasibility of PST by using the
      developed manual (Psychological Short-Term Intervention PST for Patients During
      HSCT). Based on this, it is conceivable to implement this intervention in similar
      situations to the advantage of a different patient clientele. 

PMID- 25751367
TI  - Solvents effects on charge transfer from quantum dots.
AB  - To predict and understand the performance of nanodevices in different
      environments, the influence of the solvent must be explicitly understood. In this
      Communication, this important but largely unexplored question is addressed
      through a comparison of quantum dot charge transfer processes occurring in both
      liquid phase and in vacuum. By comparing solution phase transient absorption
      spectroscopy and gas-phase photoelectron spectroscopy, we show that hexane, a
      common nonpolar solvent for quantum dots, has negligible influence on charge
      transfer dynamics. Our experimental results, supported by insights from theory,
      indicate that the reorganization energy of nonpolar solvents plays a minimal role
      in the energy landscape of charge transfer in quantum dot devices. Thus, this
      study demonstrates that measurements conducted in nonpolar solvents can indeed
      provide insight into nanodevice performance in a wide variety of environments. 

PMID- 25751369
TI  - Benefits of exercise for body, mind, and spirit.

PMID- 25751368
TI  - Temozolomide nanoparticles for targeted glioblastoma therapy.
AB  - Glioblastoma (GBM) is a deadly and debilitating brain tumor with an abysmal
      prognosis. The standard therapy for GBM is surgery followed by radiation and
      chemotherapy with Temozolomide (TMZ). Treatment of GBMs remains a challenge,
      largely because of the fast degradation of TMZ, the inability to deliver an
      effective dose of TMZ to tumors, and a lack of target specificity that may cause
      systemic toxicity. Here, we present a simple method for synthesizing a
      nanoparticle-based carrier that can protect TMZ from rapid degradation in
      physiological solutions and can specifically deliver them to GBM cells through
      the mediation of a tumor-targeting peptide chlorotoxin (CTX). Our nanoparticle,
      namely NP-TMZ-CTX, had a hydrodynamic size of <100 nm, exhibited sustained
      stability in cell culture media for up to 2 weeks, and could accommodate stable
      drug loading. TMZ bound to nanoparticles showed a much higher stability at
      physiological pH, with a half-life 7-fold greater than that of free TMZ. NP-TMZ
      CTX was able to target GBM cells and achieved 2-6-fold higher uptake and a 50-90%
      reduction of IC50 72 h post-treatment as compared to nontargeted NP-TMZ. NP-TMZ
      CTX showed great promise in its ability to deliver a large therapeutic dose of
      TMZ to GBM cells and could serve as a template for targeted delivery of other
      therapeutics. 

PMID- 25751370
TI  - George Miller's magical number of immediate memory in retrospect: Observations on
      the faltering progression of science.
AB  - Miller's (1956) article about storage capacity limits, "The Magical Number Seven
      Plus or Minus Two . . .," is one of the best-known articles in psychology. Though
      influential in several ways, for about 40 years it was oddly followed by rather
      little research on the numerical limit of capacity in working memory, or on the
      relation between 3 potentially related phenomena that Miller described. Given
      that the article was written in a humorous tone and was framed around a tongue-in
      cheek premise (persecution by an integer), I argue that it may have inadvertently
      stymied progress on these topics as researchers attempted to avoid ridicule. This
      commentary relates some correspondence with Miller on his article and concludes
      with a call to avoid self-censorship of our less conventional ideas. (PsycINFO
      Database Record 

PMID- 25751371
TI  - Gastroesophageal Reflux Disease: Cross-Sectional Study Demonstrating Rising
      Prevalence in a Chinese Population.
AB  - BACKGROUND AND AIMS: The prevalence of gastroesophageal reflux disease (GERD) is
      consistently lower in the Chinese than in white populations. Population-based
      data tracking the time trend of GERD prevalence in Chinese subjects is
      conflicting. This study examines the population prevalence, risk factors, and
      time trend associated with GERD in a Chinese population. METHODS: A population
      based cross-sectional study utilizing a validated GERD questionnaire administered
      by a telephone survey was performed on 3360 Chinese subjects from Hong Kong. GERD
      prevalence rates in 2011 were compared with prevalence rates in 2002 and 2006.
      Multiple logistic regressions were performed to determine the risk factors
      associated with weekly GERD. RESULTS: A total of 2074 subjects (mean age, 48.1+/
      18.2 y; range 18 to 94; 63.1% female) completed the survey (response rate 61.7%).
      The prevalence of GERD as defined by the Montreal definition was 3.8%. The
      prevalence of weekly GERD had increased by 1.3% between 2002 and 2011, which
      represents an at least 50% relative increase (P<0.0005). A diagnosis of weekly
      GERD was associated with noncardiac chest pain [odds ratio (OR), 1.7; 95%
      confidence interval (CI), 1.034-2.9; P=0.037], dyspepsia (OR, 5.1; 95% CI, 3.0
      8.8; P<0.005), and an acid feeling in the stomach (OR, 3.0; 95% CI, 1.8-5.1).
      CONCLUSIONS: GERD rates in the ethnic Chinese have risen over the last decade.
      Despite this, variables associated with a survey diagnosis of GERD remain
      ostensibly unchanged. GERD research in East Asia should focus on the factors
      driving the rapid rise in prevalence rates and the association with more atypical
      symptoms of GERD.

PMID- 25751372
TI  - The Effect of Hepatocellular Carcinoma Surveillance in an Urban Population With
      Liver Cirrhosis.
AB  - BACKGROUND: Hepatocellular carcinoma (HCC) surveillance in patients with
      cirrhosis is aimed at early detection so that effective therapeutic options may
      be offered. We undertook this study to assess the patterns of surveillance that
      had been offered to HCC patients evaluated at our center, and the effect of these
      strategies on outcome. METHODS: Consecutive patients, age 18 years and older,
      diagnosed with HCC between December 2007 and December 2012 were identified.
      Surveillance was defined as alpha-fetoprotein measurement and/or imaging
      examination in the 12 months before HCC diagnosis. Logistic regression and
      survival analysis models were utilized to investigate the association of
      surveillance with patient characteristics and survival. RESULTS: A total of 305
      patients with HCC and a background of cirrhosis were analyzed. HCC was detected
      by surveillance in 131 patients (43%). Of those who underwent surveillance, 92%
      were diagnosed with early-stage cancer (stages I and II) compared with 62% of
      those who did not undergo surveillance (P<0.001). The rate of surgical therapy
      (hepatic resection and liver transplantation) was almost doubled in the
      surveillance group (61% vs. 33%, P<0.05). At median follow-up of 27.3 months,
      overall survival was high at 55% and surveillance was significantly associated
      with longer survival (P=0.006). CONCLUSIONS: At our center, surveillance efficacy
      for HCC detection was notably higher than earlier reported. IMPACT: Patients who
      underwent surveillance were more likely to have their tumors detected at an early
      stage, to qualify for surgical therapy, and to have improved survival.

PMID- 25751373
TI  - New Classification of Gastric Pit Patterns and Vessel Architecture Using Probe
      based Confocal Laser Endomicroscopy.
AB  - GOALS: To propose a new probe-based confocal laser endomicroscopy (pCLE)
      classification of gastric pit patterns and vessel architecture, and to assess the
      accuracy and interobserver agreement. BACKGROUND: pCLE is a newly developed
      endoscopic device that allows the application of laser microscopy with any
      conventional endoscope and mosaic imaging. STUDY: A total of 291 pCLE videos from
      32 patients were recruited in phase I to establish the new pCLE image
      classification in the stomach. Eligible patients were then prospectively
      investigated by pCLE using the newly established classification system. All
      patients were examined first with high-definition endoscopy followed by pCLE at 7
      standardized locations and endoscopic-suspected lesions. Targeted biopsies were
      performed with precise matching of pCLE recordings. RESULTS: The sensitivity and
      specificity of type 2b pit pattern for predicting atrophic gastritis were 88.51%
      and 99.19%, respectively. The sensitivity and specificity of type 2c pit pattern
      for predicting intestinal metaplasia were 92.34% and 99.34%, respectively. The
      overall sensitivity and specificity of type 3 pit pattern or vessel architecture
      for predicting neoplasia were 89.89% and 99.44%, respectively. The interobserver
      agreement was "substantial" (kappa=0.70) for the differentiation of neoplasia
      versus non-neoplasia. CONCLUSIONS: The new pCLE classification system in the
      stomach correlates well with specific pathologic conditions and is reproducible
      by multiple investigators. Multicenter researches are warranted to further
      validate its value in clinical practice.

PMID- 25751374
TI  - Lifestyle-related factors associated with successful weight loss.
AB  - BACKGROUND: Short-term weight loss is often successful, but the obtained results
      are difficult to maintain. Therefore, a study focusing on obese people who
      successfully lost weight, with special emphasis upon methods applied and
      background factors, is of major importance. METHODS/SUBJECTS: This study was
      based upon a web-based questionnaire, which the participants filled in after
      registration. Altogether 316 people were recruited through articles in newspapers
      all over Finland, and of them 184 met the inclusion criteria: age 18-60 years,
      body mass index (BMI) >= 30 kg/m(2) before weight loss, a weight loss of at least
      10%, and maintaining it for a minimum of 2 years. RESULTS: A total of 158
      participants (100 women and 58 men) were included in the final analyses. The mean
      age was 44.5 years, average BMI before weight loss 35.9 kg/m(2) and after weight
      loss 26.1 kg/m(2), average weight loss was 26.5% or 32.4 kg. Compared with the
      general Finnish population the participants smoked less (P = 0.009), used less
      alcohol (P <= 0.001), and were physically more active (P <= 0.001). CONCLUSIONS:
      People who were successful in long-term weight loss have a much healthier
      lifestyle than the general Finnish population. Increased physical activity seems
      to be a major determinant of successful long-term results.

PMID- 25751375
TI  - Connectedness and Perceived Burdensomeness among Adolescents at Elevated Suicide
      Risk: An Examination of the Interpersonal Theory of Suicidal Behavior.
AB  - The interpersonal theory of suicidal behavior emphasizes the constructs of
      perceived burdensomeness, thwarted belongingness, and acquired capacity, which
      warrant investigation in adolescents at risk for suicide due to interpersonal
      stressors. This study examined one component of the interpersonal theory of
      suicidal behavior, "suicidal desire" (suicidal ideation), in 129 adolescents (12
      15 years) recruited from a general medical emergency department who screened
      positive for bully victimization, bully perpetration, or low interpersonal
      connectedness. Greater perceived burdensomeness combined with low family
      connectedness was a significant predictor of suicidal ideation. This suggests the
      importance of addressing connectedness and perceptions of burdensomeness in
      prevention and early intervention efforts with at-risk adolescents. 

PMID- 25751376
TI  - Microbial respiration and natural attenuation of benzene contaminated soils
      investigated by cavity enhanced Raman multi-gas spectroscopy.
AB  - Soil and groundwater contamination with benzene can cause serious environmental
      damage. However, many soil microorganisms are capable to adapt and are known to
      strongly control the fate of organic contamination. Innovative cavity enhanced
      Raman multi-gas spectroscopy (CERS) was applied to investigate the short-term
      response of the soil micro-flora to sudden surface contamination with benzene
      regarding the temporal variations of gas products and their exchange rates with
      the adjacent atmosphere. (13)C-labeled benzene was spiked on a silty-loamy soil
      column in order to track and separate the changes in heterotrophic soil
      respiration - involving (12)CO2 and O2- from the natural attenuation process of
      benzene degradation to ultimately form (13)CO2. The respiratory quotient (RQ)
      decreased from a value 0.98 to 0.46 directly after the spiking and increased
      again within 33 hours to a value of 0.72. This coincided with the maximum (13)CO2
      concentration rate (0.63 MUmol m(-2) s(-1)), indicating the highest benzene
      degradation at 33 hours after the spiking event. The diffusion of benzene in the
      headspace and the biodegradation into (13)CO2 were simultaneously monitored and
      12 days after the benzene spiking no measurable degradation was detected anymore.
      The RQ finally returned to a value of 0.96 demonstrating the reestablished
      aerobic respiration. 

PMID- 25751377
TI  - Identification of novel vaccine candidates against Acinetobacter baumannii using
      reverse vaccinology.
AB  - Acinetobacter baumannii (Ab) is a global emerging bacterium causing nosocomial
      infections such as pneumonia, meningitis, bacteremia and soft tissue infections
      especially in intensive care units. Since Ab is resistant to almost all
      conventional antibiotics, it is now one of the 6 top-priorities of the dangerous
      microorganisms listed by the Infectious Disease Society of America. The
      development of vaccine is one of the most promising and cost-effective strategies
      to prevent infections. In this study, we identified potential protective vaccine
      candidates using reverse vaccinology. We have analyzed 14 on-line available Ab
      genome sequences and found 2752 homologous core genes. Using information obtained
      from immuno-proteomic experiments, published proteomic information and the
      bioinformatics PSORTb v3.0 software to predict the location of extracellular
      and/or outer membrane proteins, 77 genes were identified and selected for further
      studies. After excluding those antigens have been used as vaccine candidates
      reported by the in silico search-engines of PubMed and Google Scholar, 13
      proteins could potentially be vaccine candidates. We have selected and cloned the
      genes of 3 antigens that were further expressed and purified. These antigens were
      found to be highly immunogenic and conferred partial protection (60%) in a
      pneumonia animal model. The strategy described in the present study incorporates
      the advantages of reverse vaccinology, bioinformatics and immuno-proteomic
      platform technologies and is easy to perform to identify novel immunogens for
      multi-component vaccines development. 

PMID- 25751378
TI  - Hazelnut Allergens: Molecular Characterization, Detection, and Clinical
      Relevance.
AB  - In last few years, special attention has been given to food-induced allergies, in
      which hazelnut allergy is highlighted. Hazelnut is one of the most commonly
      consumed tree nuts, being largely used by the food industry in a variety of
      processed foods. It has been regarded as a food with potential health benefits,
      but also as a source of allergens capable of inducing mild to severe allergic
      reactions in sensitized individuals. Considering the great number of reports
      addressing hazelnut allergens, with an estimated increasing trend, this review
      intends to assemble all the relevant information available so far on the
      following main issues: prevalence of tree nut allergy, clinical threshold levels,
      molecular characterization of hazelnut allergens (Cor a 1, Cor a 2, Cor a 8, Cor
      a 9, Cor a 10, Cor a 11, Cor a 12, Cor a 14, and Cor a TLP) and their clinical
      relevance, and methodologies for detection of hazelnut allergens in foods. A
      comprehensive overview of the current data about the molecular characterization
      of hazelnut allergens is presented, relating to biochemical classification and
      biological function with clinical importance. Recent advances in hazelnut
      allergen detection methodologies are summarized and compared, including all the
      novel protein-based and DNA-based approaches.

PMID- 25751379
TI  - [Clinical observation of telbivudine's antiviral efficacy and protection against
      mother-to-infant transmission of chronic hepatitis B during the first trimester
      of pregnancy].
AB  - OBJECTIVE: To explore the antiviral efficacy, safety and protective ability
      against mother-to-infant transmission of telbivudine in pregnant patients with
      chronic hepatitis B (CHB) during the first trimester. METHODS: Eighty four gravid
      women who were diagnosed with CHB, in their first trimester of pregnancy, and had
      refused to terminate their pregnancies were enrolled; all study participants were
      clinically classified as active hepatitis cases with positivity for both
      hepatitis B surface antigen (HBsAg) and hepatitis B e antigen (HBeAg), HBV DNA
      more than or equal to 107 copies/mL and serum level of alanine aminotarnsferase
      (ALT) of more than or equal to 4 ULN.Patients with YMDD mutations were excluded
      from the study. The study participants were divided into a telbivudine treatment
      group (n=43; administered in the first trimester of pregnancy) and a control
      group (n=41, consisting of patients who refused to take antivirals). All babies
      bom to the women in both groups of the study received standard immune prevention
      (anti-hepatitis B immunoglobulin plus hepatitis B vaccine) and artificial
      feeding.Data recorded for the women during pregnancy included clinical findings
      for tests of hepatic and renal function, myocardial enzymes, blood and urine
      clinical parameters, hepatitis B virus makers and HBV DNA, as well as notation of
      any adverse reactions. The neonates were evaluated for presence of HBV infection,
      parameters of growth and development, presence of complications, and Apgar score.
      At 6 and 12 months old, all infants were evaluated for HBV DNA level and HBsAg
      presence. RESULTS: The genetic variant rtM204I was detected in one of the women
      in the treatment group at 36 weeks of pregnancy. One woman in the control group
      developed severe hepatitis at 28 weeks of pregnancy and was put on the
      telbivudine treatment The treatment group showed greater recovery rates of ALT
      than the control group at 12 weeks of pregnancy (62.8% vs.29.3%, P=0.002), 24
      weeks of pregnancy (76.7% vs.46.3%, P=0.000), and at ante partum (88.1% vs.60.0%,
      P=0.004). The treatment group also showed greater HBV DNA-negative conversion
      rates at 12 weeks of pregnancy (20.9% vs.0, P=0.006), at 24 weeks of pregnancy
      (37.2% vs.0, P=0.001) and at ante partum (78.6% vs.0, P=0.000), and greater HBeAg
      seroconversion rates at 12 weeks of pregnancy (2.3% vs.0, P=1.000), at 24 weeks
      of pregnancy (9.3% vs.0, P=0.116) and at ante partum (2 1.4% vs.0, P=0.002). The
      HBsAg-positive rates and HBV DNA-positive rates among the infants born to the
      mothers in the treatment and control groups, respectively, were 2.4% vs.17.5%
      (P=0.027) at birth, 0 vs.17.5% (P=0.005)at 6 months old and 0 vs.17.5% (P=0.005)
      at 12 months old. The Apgar scores were not significantly different for the
      children born to the mothers from the two groups, and all the children showed
      parameters of growth development within normal limits. CONCLUSION: Telbivudine
      administration in the first trimester had a good antiviral curative effect and
      effectively blocked mother-to-infant transmission in women with CHB. The
      treatment was safe, causing no obvious adverse reaction in the gravid women or
      developmental effects on the infants.

PMID- 25751380
TI  - [Clinical features and gene mutation profiles of patients with chronic hepatitis
      B and Gilbert's syndrome].
AB  - OBJECTIVE: To explore the clinical features and gene mutation profiles of
      patients with chronic hepatitis B (CHB) and Gilbert's syndrome. METHODS: Thirty
      three patients with CHB and Gilbert's syndrome were enrolled in the study. Serum
      markers of liver function and histological features of disease-related liver
      injury were assessed by standard methods. Gene mutations were detected by PCR and
      direct DNA sequencing.Statistical analysis was carried out with the chi-square
      and t tests. RESULTS: Sequencing of the Gilbert syndrome-associated gene, UGT 1A
      1, revealed mutations in the upstream promoter phenobarbital-responsive element
      module (PBREM) (-3279 mutation, 23 cases), in the promoter TATA box (a TA
      insertion mutation, 21 cases), and in the coding region of exon 1 (a GGA-AGA
      Gly71Arg mutation, 18 cases); there was no statistical difference found for any
      of the three mutations among this patient population (x2 =1.640, P more than
      0.05). CONCLUSION: The traditional methods of diagnosis for patients with CHB and
      Gilbert's syndrome remain a technical challenge in the clinic, and gene detection
      may represent a more favorable method for diagnosing this patient population.

PMID- 25751381
TI  - [Nucleoside analogues for acute-on-chronic liver failure associated with
      hepatitis B virus infection: a 24-month survival analysis].
AB  - OBJECTIVE: To investigate the effect of different nucleoside analogues on the
      long-term survival rate of patients with acute-on-chronic liver failure (ACLF)
      associated with hepatitis B virus (HBV) infection. METHODS: One hundred and
      eighty patients with HBV-related ACLF were enrolled in this prospective cohort
      study and divided into a basic treatment group (n=30) and an antiviral treatment
      group, the latter of which was further subdivided into the lamivudine treatment
      group (n=66), telbivudine treatment group (n=38) and entecavir treatment group
      (n=46) according to voluntary choice by the patient.All study participants were
      followed-up for 24 months. The Kaplan-Meier method was applied for survival
      analysis. RESULTS: The patients in the four antiviral treatment groups had
      statistically similar baseline clinical characteristics and 1-month survival
      rates (Breslow =4.475, P=0.215).However, the basic treatment group had a
      significantly lower survival rate than the antiviral treatment groups that
      received lamivudine, telbivudine, or entecavir (all P less than 0.05) at the
      treatment periods of 2, 3, 6, 12 and 18-months; however, these three treatment
      groups showed no significant differences in survival rates. At the time point of
      24 months of treatment, the basic treatment group retained its lower rate of
      survival than the three antiviral treated groups (lamivudine:Breslow =5.604,
      P=0.018; telbivudine:Breslow =5.621, P=0.018; entecavir:Breslow =14.701, P less
      than 0.001); while the survival rates were similar for the lamivudine treatment
      group and the telbivudine treatment group at this time point, their survival
      rates were significantly lower than that of the entecavir treatment group
      (Breslow =4.010, P=0.045; Breslow =4.307, P=0.038).Stratification analysis showed
      that when the baseline was 30 less than PTA less than or equal to 40 or MELD less
      than or equal to 29 or HBV DNA more than or equal to 5 log10 IU/mL, the
      cumulative survival rates of the basic treatment group and antiviral treatment
      group were statistically similar even though the patients had completed 1 month
      of treatment After being treated for 2, 3, 6, 12, 18 and 24 months, the
      cumulative survival rates of the basic treatment group were consistently below
      those of the overall antiviral treatment group (P less than 0.05). The cumulative
      survival rate of the basic treatment group followed-up for 1 to 24 months, with
      PTA values between 20 and 30, was lower than that of the overall antiviral
      treatment group (P less than 0.05); two groups of patients with PTA less than or
      equal to 20 or MELD more than or equal to 30 were followed-up for 1 months to 24
      months, and their cumulative survival rates showed no significant difference (P
      more than 0.05). Among the patients whose baseline was HBV DNA less than 5 log10
      IU/mL, the comparison of survival rates between the basic treatment group and the
      overall antiviral treatment group showed no significant differences after
      treatment for 1, 2, 3, 6, 12 or 18 months, and the survival rate was lower than
      that of the overall antiviral treatment group (Breslow =4.055, P=0.044) after 24
      months. CONCLUSION: Nucleoside analogues can improve the long-term survival rate
      of HBV-related ACLF patients.Entecavir is preferred for the long-term treatment
      of these patients.Patients in the early and middle stages of this disease and HBV
      DNA-positive patients should adopt antiviral treatment as early as possible.

PMID- 25751382
TI  - [Clinical emergence features and implications of hepatitis B virus rtA181T
      mutation].
AB  - OBJECTIVE: To determine the mutational profile and clinical implications of the
      viral reverse-transcriptase (rt)A 181T mutation in hepatitis B virus (HBV)
      through population-based analysis of clinical samples. METHODS: Serum samples
      from 3, 013 patients who visited The 302 Hospital (Beijing, China) were
      investigated.HBV DNA was extracted and HBV mutations and genotypes were
      determined by direct sequencing.Recombinant plasmids harboring the rtA181T/sW172*
      mutant or wild type sequence were constructed and transfected into the HepG2 cell
      line. The levels of HBsAg in culture supernatants were compared and statistically
      analyzed. RESULTS: The incidence of rtA181T across the study population was 4.1%
      (165/3, 013), and most of the rtAl 81T-positive patients had received adefovir
      and/or lamivudine.Forty percent (66/165) of the rtA 181T cases were single
      mutants and treatment responsive, 46.1% (76/165) included the adefovir-resistant
      mutation rtA 181 V/N236T, 12.1% (20/165) included the lamivudine-resistant
      mutation rtM204V/rtM2041, and 1.8% (3/165) included multidrug-resistant
      mutations.Interestingly, 73.9% (122/165) of the rtA181T-positive samples were
      detected with co-existing wild-type nucleotides at the site. The rates of HBV/C
      to HBV/B were 92.1% to 7.9% in the rtA181T-positive patients, but 82.1% to 17.9%
      in the rtA181T-negative paticnts (P less than 0.01).Almost all (98.2%; 129/165)
      of the rtA181T led to sW172*, while only 1.8% of the rtA181T (3/165) led to
      sW172L or sW172S.HBsAg secretion in vitro was reduced from the rtA181T/ sW172*
      strain, but there was no significant difference observed in the average serum
      HBsAg and HBV DNA levels of patients who carried or did not carry the mutant.
      CONCLUSION: The HBV rtA181T mutation is closely associated with adefovir and
      lamivudine exposure.rtA181T may led to sW172*, culminating in suppression of
      HBsAg secretion.However, co-existence of the mutant with wild-type sequences was
      common among our patient population, suggesting that the mutation had little
      impact on serum HBsAg and HBV DNA levels across the clinical study population.

PMID- 25751383
TI  - [Pharmacoeconomic evaluation of treatments based on antiretrovirals for HBeAg
      negative chronic hepatitis B].
AB  - OBJECTIVE: To evaluate long-term cost-effectiveness of nucleoside analogues and
      peg-interferon alfa-2a (peg-IFNa2a) for the treatment of chronic hepatitis B
      (CHB) in hepatitis B e antigen (HBeAg)-negative patients. METHODS: A multi-health
      slate Markov model was developed based on the disease progression pattern to
      estimate the long-term effect and medical expense of different treatments for
      HBeAg-negative CHB.Incremental cost-effectiveness analysis was then carried out.
      RESULTS: In comparison with no antiretroviral treatment, all of the
      antiretroviral treatments were capable of prolonging CHB patients' life years.In
      particular, entecavir plus adefovir dipivoxil combination therapy showed the best
      2 year survival, with expected life-years and quality-adjusted life-years (QALYs)
      being 19.59 years and 10.12 years, respectively, which were 1.46 years and 1.12
      years better than with no antiretroviral treatment. The most cost-effective
      treatment for HBeAg-negative CHB was lamivudine plus adefovir dipivoxil rescue
      therapy, as it prolonged survival by 0.95 QALYs with an additional 15459 yuan;
      the incremental medical cost for gaining 1 QALY was 16273 yuan. CONCLUSION: Among
      the antiretroviral medicines applied as therapy for HBeAg-negative CHB in China,
      the most effective treatment is entecavir plus adefovir dipivoxil rescue therapy
      and the most cost-effective treatment is lamivudine plus adefovir dipivoxil
      rescue therapy.

PMID- 25751384
TI  - [Clinical profiles of circulating plasmacytoid dendritic cells in chronic
      hepatitis B patients in response to pegylated-interferon alfa-2a treatment].
AB  - OBJECTIVE: To investigate the changes in circulating plasmacytoid dendritic cells
      (pDCs) in patients with chronic hepatitis B (CHB) during the course of treatment
      with pegylated-interferon alfa-2s (peg-IFNa-2a) and to determine the correlations
      with therapeutic response. METHODS: Forty-one patients with CHB who were
      receiving peg-IFNa-2a antiviral treatment for 48 weeks were enrolled in the
      study.Expression of the Toll-like receptor 9 (TLR9) on and frequency and
      functionality of the pDCs were analyzed at treatment weeks 0, 2, 12, 24, 36 and
      48. RESULTS: All patients exhibited an initially rapid decrease in the numbers of
      circulating pDCs and showed CpG-induced endogenous IFNa production within the
      first 2 weeks of treatment.Subsequently, all responders displayed a continuous
      increase in pDC numbers as well as functionality, both of which peaked around
      week 12 of treatment; in addition, these treatment responses were accompanied by
      significantly increased levels of type 1 T helper cytokines (P less than 0.05),
      which did not occur in the non-responders. CONCLUSION: pDCs are involved in the
      initial therapeutic immune response stimulated by peg-IFNa-2a treatment.Recovery
      of blood pDC number and functionality may represent a predictor of favorable
      response to peg-IFNa-2a antiviral treatment in patients with CHB.

PMID- 25751385
TI  - [Clinical significance of serum HBsAg levels, HBsAg/HBV DNA ratio, and
      association with liver inflammation activity in HBeAg-positive chronic hepatitis
      B].
AB  - OBJECTIVE: To study the clinical significance of hepatitis B surface antigen
      (HBsAg) levels and HBsAg/hepatitis B virus (HBV) DNA ratio in relation to liver
      inflammation in HBeAg-positive chronic hepatitis B (CHB). METHODS: One hundred
      and fifty-three Chinese patients with chronic HBV infection with HBeAg-positive
      status were enrolled in the study.Quantitative measurements were made for HBsAg
      levels by immunoassay (Architect HBsAg QT by Abbott Diagnostic) and HBV DNA by
      real-time fluorescence quantitative PCR.Levels of liver function markers were
      measured by standard methods.Liver biopsy specimens were obtained from all
      patients and used to score the histology (liver inflammation) activity index
      (HAI) and grade (G) the extent of necroinflammation.Statistical correlation
      analysis was performed to determine the association of HBsAg titre or HBsAg/HBV
      DNA ratio with the various parameters of liver injury. RESULTS: HBsAg titre and
      HBsAg/HBV DNA ratio were significantly correlated (r =0.578, P less than
      0.0001).A significant positive correlation (r =0.642, P less than 0.0001) was
      found between HBsAg titre and HBV DNA load, and a significant negative
      correlation was found between the HAI and HBsAg (r =-0.389, P less than 0.0001)
      and HBsAg/HBV DNA ratio (r =-0.307, P=0.000l).A significant positive correlation
      was found between alanine aminotransferase (ALT) level and the HAI (r =0.480, P
      less than 0.0001).Patients with G less than 2 necroinflammation had significantly
      higher HBsAg titre and HBsAg/HBV DNA ratio than patients with G more than or
      equal to 2 necroinflammation (both P less than 0.01) but similar levels ofHBV
      DNA.Generation of a receiver operating characteristic curve using G more than or
      equal to 2 as the positive index provided the following area under the curve
      (AUC) values:HBsAg titre, 0.700; HBsAg/HBV DNA ratio, 0.672; ALT level,
      0.713.When the random chance AUC was 0.5, all levels of AUC were statistically
      significant (Pless than 0.001).HBsAg titre (sensitivity =76.92%) was more
      sensitive than ALT level (sensitivity =76.92%), and HBsAg/HBV DNA ratio
      (specificity =81.33%) was more specific than ALT level (specificity
      =81.33%).Youden's index for comprehensive evaluation using ALT was higher than
      those for HBsAg titre or HBsAg/HBV DNA ratio.When HBsAg and ALT were considered
      in parallel, the sensitivity increased to 94.08% and specificity rose to 85.60%.
      CONCLUSION: HBsAg titre, HBsAg/HBV DNA ratio and ALT levels can be used as the
      index for judging the degree of liver inflammation in HBeAg-positive CHB
      patients.Higher sensitivity and specificity are attained when HBsAg and ALT are
      used in series or parallel.

PMID- 25751386
TI  - [Esophageal and gastric variceal bleeding in the prevention of early rebleeding
      given enteral nutrition value after endoscopic variceal ligation and treatment].
AB  - OBJECTIVE: To observe liver cirrhosis with esophageal and gastric variceal
      bleeding (GEVB) after endoscopic variceal ligation and treatment of early oral
      nutrition liquid in patients administered to reduce the risk of early rebleeding.
      METHODS: Seventy-eight patients with cirrhosis who received therapeutic endoscopy
      after GEVB and who suffered from malnutrition were randomly divided into a
      treatment group (oral solution group, n=40) and a control group (regular diet
      group, n=38).Both of the two groups received food at 12 hours after therapeutic
      endoscopy.After 14 days, the rates of early rebleeding rate and liver function
      recovery were compared for the two groups. T-test, rank test, chi-square test and
      Fisher's exact test were used for statistical analyses. RESULTS: Compared with
      the control group, less patients in the treatment group experienced rebleeding
      (0/40 vs. 5/38; x2=5.624, P=0.018); the treatment group also showed significantly
      improved indexes of liver function (all P less than 0.05). CONCLUSION: s GEVB
      after endoscopic treatment with early oral nutrition liquid administration can
      reduce in the early rebleeding risk and improve function and malnutrition status.

PMID- 25751387
TI  - [Clinical application of hepatic venous pressure gradient to predict early
      bleeding after esophageal variceal ligation].
AB  - OBJECTIVE: To investigate the predictive value of hepatic venous pressure
      gradient (HVPG) for early bleeding after esophageal variceal ligation (EVL) by
      analyzing the differences in HVPG in patients with and without post-EVL bleeding.
      METHODS: The medical records of patients who had been diagnosed with cirrhosis
      and esophageal varices and who had pre-EVL HVPG measurement data were surveyed.
      The study population included 105 patients from October 2010 to March 2014. Data
      of HVPG value, previous treatment history, endoscopic manifestation, and whether
      bleeding and serious complications occurred within 2 weeks after the ligation
      procedure were investigated as independent risk factors. STATISTICAL METHODS:
      included the chi-square test and Wilcoxon test, logistic regression modeling and
      receiver operating characteristic (ROC) analysis using the SPSS software version
      16. RESULTS: Only HVPG value was identified as an independent risk factor of
      early bleeding after EVL.According to the ROC analysis, the area under the curve
      (AUC) of HVPG for early bleeding after EVL was 0.866; when HVPG was more than or
      equal to 16 mmHg, AUC was 0.838. The sensitivity was 90.9% and the specificity
      was 76.4%. CONCLUSION: HVPG is an independent factor of early bleeding after EVL
      and when HVPG cut-off value of more than or equal to 16 mmHg is used the
      predictive ability has certain accuracy and high sensitivity and specificity.

PMID- 25751388
TI  - [Predictive value of liver enzymes and alcohol consumption for risk of type 2
      diabetes].
AB  - OBJECTIVE: To compare the predictive value of liver enzymes and alcohol
      consumption for determining risk of type 2 diabetes (T2DM). METHODS: A cross
      sectional study was conducted in Zhengzhou with a total of 2, 693
      men.Participants' height, weight, and histories of smoking and drinking were
      recorded. Levels of alanine aminotransferase (ALT), aspartate aminotransferase
      (AST), gamma-glutamyl transferase (GGT) and blood glucose, as well as related
      metabolic indexes were detected. RESULTS: Moderate daily alcohol consumption
      (more than 35 g ethanol/week and less than 140 g ethanol/week) decreased the risk
      of type 2 diabetes (OR =0.376, 95% CI:0.306 -0.463, P less than 0.05) but
      increased risk for higher levels of GGT and ALT (OR GGT =3.012, 95% CI:2.357
      3.849, Pless than 0.01; ORALT =1.473, 95% CI:1.043-2.081, Pless than 0.05). In
      joint analyses of alcohol consumption and liver enzymes, the group of
      nondrinkers/light drinkers (less than or equal to 35 g ethanol/week) in the
      fourth quartile of GGT levels had the highest risk for type 2 diabetes (OR
      =12.219, 95% CI:6.217-24.016, P less than 0.01). The relationship of ALT and
      daily alcohol consumption with the risk of type 2 diabetes was almost the same as
      that of GGT (nondrinkers/light drinkers in the fourth quartile of ALT levels (OR
      =5.357, 95% CI:3.070-9.350, P less than 0.0 1). CONCLUSION: GGT, ALT and daily
      alcohol consumption were independently associated with risk of type 2 diabetes.
      Nondrinkers/light drinkers with the highest levels ofGGT orALT were at high risk
      of type 2 diabetes.

PMID- 25751389
TI  - [Hematologic toxicity of Gynura segetum and effects on vascular endothelium in a
      rat model of hepatic veno-occlusive disease].
AB  - OBJECTIVE: To observe the effects ofGynura segetum in rats with hepatic veno
      occlusive disease (HVOD). METHODS: Sixty Sprague-Dawley rats were assigned to a
      blank control group, one of three Gynura segetum treatment groups (low-dose
      group, 5.0 g/kg; mid-dose group, 10 g/kg; high-dose group, 20 g/kg), or a pseudo
      drug group (10 g/kg of pseudo-ginseng). After 28 days of treatment, effects on
      white blood cell count, coagulation, secreted factors from vascular endothelium,
      and histopathology of the spleen were observed and inter-group differences were
      statistically assessed. RESULTS: After the 4-week administration, all rats in the
      Gynura segetum treatment groups showed decrease in body weight, increases in
      numbers of leukocytes, neutrophils, lymphocytes, monocytes and
      eosinophils.decreases in platelets and platelet hematocrit, and increases in mean
      platelet volume and platelet distribution.In addition, the Gynura segetum
      treatments increased the prothrombin time, activated partial thromboplastin time,
      thrombin time, prothrombin ratio and international normalized ratio, but
      decreased the PT%, fibrinogen level and platelet aggregation.Serum levels of
      endothelin and nitric oxide were also elevated by the Gynura segetum
      treatments.All measured parameters showed significant differences from the
      control group (P less than 0.01 or less than 0.05).Finally, the splenic follicles
      were significantly reduced and the spleens showed an absence of germinal centers
      along with a large number of diffuse lymphocytes and reduced red pulp sinusoids.
      CONCLUSION: The Gynura segetum treatment has some toxic effects; it can reduce
      platelet count and platelet hematocrit, inhibit blood clotting time and platelet
      aggregation, increase the secretion of factors from the vascular endothelium and
      disrupt spleen histology.

PMID- 25751390
TI  - [Effects and mechanisms of the inflammatory reaction related to NASH and induced
      by activation of the cholinergic anti-inflammatory pathway].
AB  - OBJECTIVE: To investigate the effects and mechanisms of the inflammatory reaction
      related to nonalcoholic steatohepatitis (NASH) and induced by activation of the
      cholinergic anti-inflammatory pathway. METHODS: A mouse model of NASH was
      established by feeding a high-fat and high-sugar diet.Activation of the
      cholinergic anti-inflammatory pathway was achieved by nicotine administration to
      the NASH modeled mice and normal controls. Liver biopsies were taken and the
      concentrations of cytokines were measured. Isolated liver primary Kupffer cells
      and RAw264.7 cells were cultured, pre-treated or not with lipopolysaccharide
      (LPS) and exposed to nicotine, after which the supernatant concentrations of IL-6
      and TNFa were determined by ELISA. The protein expression levels of
      phosphorylated (p)-NF-kB and I k B were detected in primary cultured Kupffer
      cells by western blotting. RESULTS: The mouse model of NASH was successfully
      established, as evidenced by findings from liver biopsy and serum liver function
      tests. The degree of liver inflammation in the NASH mice decreased after nicotine
      administration, and the level of serum TNFa also significantly decreased. The
      levels of serum TNFa were 21.95+/-0.8 pg/mL in nicotine-treated mice and 38.07+/
      1.7 pg/mL in the non-nicotine-treated NASH mice (P less than 0.05). The nicotine
      treatment also significantly reduced the concentration of TNFa in the culture
      supernatants of Kupffer cells after LPS stimulation; moreover, the supernatant
      level of TNFa decreased significantly after the nicotine treatment (Pless than
      0.05). LPS stimulation of the RAw264.7 cells led to an increased level ofp-NF-kB
      and a reduced level ofI-kB, suggesting that the NF-kB pathway had been activated;
      different doses of nicotine pre-treatment led to down-regulation of the p-NF-kB
      level and up-regulation of the I-kB level, both in dose-dependent manners.
      CONCLUSION: Activating the cholinergic anti-inflammatory pathway inhibits the
      NASH-related inflammatory reaction, and the mechanism for this inhibition
      involves the NF-kB signaling pathway.

PMID- 25751391
TI  - [Adiponectin inhibits oxidative stress and modulates TGF-b1 and COL-1 expression
      via the AMPK pathway in HSC-T6 cells].
AB  - OBJECTIVE: To investigate the anti-oxidative stress and anti-fibrotic mechanisms
      of adiponectin by examining effects on oxidative stress levels and expression of
      fibrosis-related signaling factors, including transforming growth factor-beta 1
      (TGFb1), collagen I (COL-1), and the adenosine monophosphate-activated protein
      kinase (AMPK) pathway by using an in vitro HSC-T6 cultured cell system. METHODS:
      Activated HSC-T6 cells were pre-treated with 1.0 mug/mL adiponectin for 0, 30, 60
      and 120 min, or left untreated to serve as controls, and both groups were then
      exposed to 5 mumol/L H2O2; a portion of the adiponectin-treated oxidative stress
      induced cells were treated with an AMPK inhibitor (Compound C). The effects on
      mRNA levels of TGFb1. and COL-1 were analyzed by real-time PCR, in the levels of
      secreted TGF-b1 and COL-1 were detected by enzyme-linked immunosorbent assay of
      supernatants, and in the phosphoAMPK and AMPK protein expressions were detected
      by Western blotting. RESULTS: Compared to the H2O2 group without adiponectin pre
      treatment, the H2O2 group with adiponectin pre-treatment showed significantly
      increased activity of superoxide dismutase (SOD), decreased content of
      malondialdehyde (MDA), and decreased gene and protein expressions of TGF-b1 and
      COL-1 (P less than 0.05). Moreover, inhibition of the AMPK pathway inhibited
      these adiponectin-mediated effects. The H2O2 group with adiponectin pre-treatment
      also showed increased levels of phospho-AMPK protein expression, with the maximum
      effect detected after 120 min of the adiponectin pre-treatment (P less than
      0.01). CONCLUSION: Inhibition of oxidative stress is one of the mechanisms of the
      anti-fibrotic effects of adiponectin. Adiponectin can attenuate oxidative stress
      levels, resulting in down-regulation of TGFb1 and COL-1 expression through
      activation of the AMPK pathway.

PMID- 25751392
TI  - Future directions for research on the development of relational and physical peer
      victimization.
AB  - After several decades of research on peer victimization and associated constructs
      the field is poised to make a number of important discoveries and advances. More
      specifically, the study of peer victimization subtypes has rapidly increased
      since the seminal work of Crick and Grotpeter ( 1996 ) on relational and physical
      victimization. The current state of the field is briefly reviewed, and
      recommendations for future directions are provided to advance our literature.
      Critical future directions are discussed and include (a) broaden the range of
      adjustment outcomes and examine differential pathways associated with physical
      and relational peer victimization; (b) study peer victimization subtypes at
      multiple levels of influence including psychophysiological and gene-environment
      interactions; (c) study physical and relational victimization outside of
      friendships and links with other close relationship systems; (d) examine the role
      of culture on peer victimization subtypes; (e) focus on context including but not
      limited to socioeconomic status; (f) test the role of gender, gender identity,
      and gender-linked self-construals; (g) explore the impact of peer group
      processes; and (h) continue to develop evidence-based programs for physical and
      relational peer victimization. Finally, the adoption of a developmental
      psychopathology framework is stressed as a means by which we may advance our
      future study of peer victimization subtypes. 

PMID- 25751393
TI  - Patient access to electronic health records during hospitalization.

PMID- 25751394
TI  - Mindin regulates vascular smooth muscle cell phenotype and prevents neointima
      formation.
AB  - Mindin/spondin 2, an extracellular matrix (ECM) component that belongs to the
      thrombospondin type 1 (TSR) class of molecules, plays prominent roles in the
      regulation of inflammatory responses, angiogenesis and metabolic disorders. Our
      most recent studies indicated that mindin is largely involved in the initiation
      and development of cardiac and cerebrovascular diseases [Zhu et al. (2014) J.
      Hepatol. 60, 1046-1054; Bian et al. (2012) J. Mol. Med. 90, 895-910; Wang et al.
      (2013) Exp. Neurol. 247, 506-516; Yan et al. (2011) Cardiovasc. Res. 92, 85-94].
      However, the regulatory functions of mindin in neointima formation remain
      unclear. In the present study, mindin expression was significantly down-regulated
      in platelet-derived growth factor-BB (PDGF-BB)-stimulated vascular smooth muscle
      cells (VSMCs) and wire injury-stimulated vascular tissue. Using a gain-of
      function approach, overexpression of mindin in VSMCs exhibited strong anti
      proliferative and anti-migratory effects on VSMCs, whereas significant
      suppression of intimal hyperplasia was observed in transgenic (TG) mice
      expressing mindin specifically in smooth muscle cells (SMCs). These mice
      exhibited blunted VSMC proliferation, migration and phenotypic switching.
      Conversely, deletion of mindin dramatically exacerbated neointima formation in a
      wire-injury mouse model, which was further confirmed in a balloon injury-induced
      vascular lesion model using a novel mindin-KO (knockout) rat strain. From a
      mechanistic standpoint, the AKT (Protein Kinase B)-GSK3beta (glycogen synthase
      kinase 3beta)/mTOR (mammalian target of rapamycin)-FOXO3A (forkhead box O)-FOXO1
      signalling axis is responsible for the regulation of mindin during intimal
      thickening. Interestingly, an AKT inhibitor largely reversed mindin-KO-induced
      aggravated hyperplasia, suggesting that mindin-mediated neointima formation is
      AKT-dependent. Taken together, our findings demonstrate that mindin protects
      against vascular hyperplasia by suppression of abnormal VSMC proliferation,
      migration and phenotypic switching in an AKT-dependent manner. Up-regulation of
      mindin might represent an effective therapy for vascular-remodelling-related
      diseases.

PMID- 25751395
TI  - Cancer pharmacogenomics: implications on ethnic diversity and drug response.
AB  - The goal of pharmacogenomic research is to discover and validate genetic variants
      that are predictive of drug response, for eventual implementation into clinical
      practice. Cancer pharmacogenomics provides the opportunity to analyze two sets of
      DNA, that of the tumor (somatic) and that of the host (germline). Germline
      variants are inherited variations and are often associated with the
      pharmacokinetic behavior of a drug, including drug disposition and ultimately
      drug efficacy and/or toxicity, whereas somatic mutations are often useful in
      predicting the pharmacodynamic response to drugs. Pharmacoethnicity, or ethnic
      diversity in drug response or toxicity, is an increasingly recognized factor
      accounting for interindividual variations in anticancer drug response.
      Pharmacoethnicity is often determined by germline pharmacogenomic factors and the
      distribution of single nucleotide polymorphisms across various populations, but
      it may also be influenced by nongenetic factors, such as environmental factors.
      This review aims to elucidate the importance of pharmacoethnicity in cancer
      pharmacogenomic research and implementation, focusing solely on germline
      variants. 

PMID- 25751396
TI  - Integrating dynamic mixed-effect modelling and penalized regression to explore
      genetic association with pharmacokinetics.
AB  - CONTEXT: In a previous work, we have shown that penalized regression approaches
      can allow many genetic variants to be incorporated into sophisticated
      pharmacokinetic (PK) models in a way that is both computationally and
      statistically efficient. The phenotypes were the individual model parameter
      estimates, obtained a posteriori of the model fit and known to be sensitive to
      the study design. OBJECTIVE: The aim of this study was to propose an integrated
      approach in which genetic effect sizes are estimated simultaneously with the PK
      model parameters, which should improve the estimate precision and reduce
      sensitivity to study design. METHODS: A total of 200 data sets were simulated
      under the null and each of the following three alternative scenarios: (i) a phase
      II study with N=300 participants and n=6 sampling times, wherein six unobserved
      causal variants affect the drug elimination clearance; (ii) the addition of
      participants with a residual concentration collected in clinical routine (N=300,
      n=6 plus N=700, n=1); and (iii) a phase II study (N=300, n=6) in which four
      unobserved causal variants affect two different model parameters. RESULTS: In all
      scenarios the integrated approach detected fewer false positives. In scenario
      (i), true-positive rates were low and the stepwise procedure outperformed the
      integrated approach. In scenario (ii), approaches performed similarly and rates
      were higher. In scenario (iii), the integrated approach outperformed the stepwise
      procedure. CONCLUSION: A PK phase II study with N=300 lacks the power to detect
      genetic effects on PK using genetic arrays. Our approach can simultaneously
      analyse phase II and clinical routine data and identify when genetic variants
      affect multiple PK parameters.

PMID- 25751398
TI  - Hypothalamic-pituitary-adrenal system, neurotrophic factors and clozapine
      response: association with FKBP5 and NTRK2 genes.
AB  - Clozapine is an atypical antipsychotic drug known as being more effective
      compared with traditional antipsychotics for patients with poor response or
      resistance to treatment. It has been demonstrated that clozapine modulates
      hypothalamic-pituitary-adrenal activity and affects central brain-derived
      neurotrophic factor levels, which could explain part of its therapeutic efficacy.
      In this study, we investigated the role of genes related to the hypothalamic
      pituitary-adrenal axis (FKBP5 and NR3C1) and neurotrophic factors (BDNF and
      NTRK2) in clinical response to clozapine in 591 schizophrenia patients. We found
      significant allelic and genotype associations between FKBP5-rs1360780, NTRK2
      rs1778929 and NTRK2-rs10465180 polymorphisms and clozapine response. The
      haplotypes composed of rs1360780-rs3777747-rs17542466-rs2766533 (FKBP5) and
      rs1619120-rs1778929-rs10465180 (NTRK2) were also nominally significant. Our
      results suggest that genetic variability in FKBP5 and NTRK2 genes may partially
      explain clinical response to clozapine. Further studies are needed to clarify the
      involvement of these genes in clinical response to atypical antipsychotics. 

PMID- 25751397
TI  - Impact of HSD11B1 polymorphisms on BMI and components of the metabolic syndrome
      in patients receiving psychotropic treatments.
AB  - BACKGROUND: Metabolic syndrome (MetS) associated with psychiatric disorders and
      psychotropic treatments represents a major health issue. 11beta-Hydroxysteroid
      dehydrogenase type 1 (11beta-HSD1) is an enzyme that catalyzes tissue
      regeneration of active cortisol from cortisone. Elevated enzymatic activity of
      11beta-HSD1 may lead to the development of MetS. METHODS: We investigated the
      association between seven HSD11B1 gene (encoding 11beta-HSD1) polymorphisms and
      BMI and MetS components in a psychiatric sample treated with potential weight
      gain-inducing psychotropic drugs (n=478). The polymorphisms that survived
      Bonferroni correction were analyzed in two independent psychiatric samples
      (nR1=168, nR2=188) and in several large population-based samples (n1=5338; n2=123
      865; n3>100 000). RESULTS: HSD11B1 rs846910-A, rs375319-A, and rs4844488-G allele
      carriers were found to be associated with lower BMI, waist circumference, and
      diastolic blood pressure compared with the reference genotype (Pcorrected<0.05).
      These associations were exclusively detected in women (n=257) with more than 3.1
      kg/m, 7.5 cm, and 4.2 mmHg lower BMI, waist circumference, and diastolic blood
      pressure, respectively, in rs846910-A, rs375319-A, and rs4844488-G allele
      carriers compared with noncarriers (Pcorrected<0.05). Conversely, carriers of the
      rs846906-T allele had significantly higher waist circumference and triglycerides
      and lower high-density lipoprotein-cholesterol exclusively in men
      (Pcorrected=0.028). The rs846906-T allele was also associated with a higher risk
      of MetS at 3 months of follow-up (odds ratio: 3.31, 95% confidence interval: 1.53
      7.17, Pcorrected=0.014). No association was observed between HSD11B1
      polymorphisms and BMI and MetS components in the population-based samples.
      CONCLUSIONS: Our results indicate that HSD11B1 polymorphisms may contribute
      toward the development of MetS in psychiatric patients treated with potential
      weight gain-inducing psychotropic drugs, but do not play a significant role in
      the general population.

PMID- 25751399
TI  - In utero exposure to diethylstilbestrol and blood DNA methylation in women ages
      40-59 years from the sister study.
AB  - In utero exposure to diethylstilbestrol (DES) has been associated with increased
      risk of adverse health outcomes such as fertility problems and vaginal as well as
      breast cancer. Animal studies have linked prenatal DES exposure to lasting DNA
      methylation changes. We investigated genome-wide DNA methylation and in utero DES
      exposure in a sample of non-Hispanic white women aged 40-59 years from the Sister
      Study, a large United States cohort study of women with a family history of
      breast cancer. Using questionnaire information from women and their mothers, we
      selected 100 women whose mothers reported taking DES while pregnant and 100
      control women whose mothers had not taken DES. DNA methylation in blood was
      measured at 485,577 CpG sites using the Illumina HumanMethylation450 BeadChip.
      Associations between CpG methylation and DES exposure status were analyzed using
      robust linear regression with adjustment for blood cell composition and multiple
      comparisons. Although four CpGs had p<105, after accounting for multiple
      comparisons using the false discovery rate (FDR), none reached genome-wide
      significance. In conclusion, adult women exposed to DES in utero had no evidence
      of large persistent changes in blood DNA methylation. 

PMID- 25751401
TI  - Aurophilicity-triggered assembly of novel cyclic penta- and hexanuclear gold(I)
      complexes with rigid anionic NHC-type ligands.
AB  - The products of the reaction between N,N'-diphosphanylimidazol-2-ylidene (P-C-P)
      and gold(I) precursors depend on the nature of the anions associated with the
      latter. In contrast to the reported reaction with [Au(tht)2(OTf)], the use of
      [AuCl(tht)] led to the new hexanuclear complex 1, which features a Au6(MU3-P
      C,kappaC,kappaN,kappaP)3 skeleton. The reaction of lithium imidazolide (P-C-Li)
      and [AuCl(tht)] also afforded 1, together with an unusual salt of the general
      formula [Au5Cl(MU3-P-C-kappaP,kappaC,kappaN)3]2[AuCl2]2 (2), which contains
      [Au5(MU3-P-C-kappaP,kappaC,kappaN)](+) subunits. In the solid state, one of these
      Au5 cations is associated with an [AuCl2](-) anion, while two other cations
      interact through their unique dicoordinated N-Au-N center with a [AuCl2](-)
      anion, with the charge of the resulting monocation being compensated for by
      another [AuCl2](-) anion to give a Au12 salt. Remarkably, the latter displays
      seven different bonding types at Au(I): C-Au-C, N-Au-N, P-Au-P, Cl-Au-Cl, C-Au-N,
      P-Au-Cl, and Au...Au. 

PMID- 25751403
TI  - Obama's Precision Medicine Initiative.

PMID- 25751402
TI  - Prevalence and correlation of infectious agents in hospitalized children with
      acute respiratory tract infections in Central China.
AB  - Acute respiratory tract infections (ARTIs) are associated with significant
      morbidity and mortality worldwide, especially in children under the age of 5
      years. Almost 2 million children die from ARTIs each year, and most of them are
      from developing countries. The prevalence and correlation of pathogens in ARTIs
      are poorly understood, but are critical for improving case prevention, treatment,
      and management. In this study, we investigated the prevalence and correlation of
      infectious agents in children with ARTIs. A total of 39,756 children with one or
      more symptoms, including fever, cough, sore throat, tonsillitis, pharyngitis,
      herpangina, pneumonia, and bronchiolitis, were enrolled in the study. All
      patients were hospitalized in Wuhan Children's Hospital between October 1, 2010
      and September 30, 2012, and were evaluated for infectious agents. Pathogens,
      including Mycoplasma pneumoniae, influenza A virus, influenza B virus,
      adenoviruses, respiratory syncytial virus, parainfluenza virus, Legionella
      pneumophila, Chlamydophila pneumoniae, and Coxiella burnetii, were screened
      simultaneously in patient blood samples using anti-pathogen IgM tests. Regression
      analysis was used to reveal correlations among the pathogens. Our results showed
      that one or more pathogens were identified in 10,206 patients, and that
      Mycoplasma pneumoniae, adenoviruses, and influenza B virus were the leading
      infectious agents. Mixed-infections of pathogens were detected in 2,391 cases,
      with Mycoplasma pneumoniae as the most frequent pathogen. The most common agents
      in the co-infections were Mycoplasma pneumoniae and influenza B virus. Regression
      analysis revealed a linear correlation between the proportion of mixed infections
      and the incidence of multi-pathogen infections. The prevalence of infectious
      agents in children with ARTIs was determined. Equations were established to
      estimate multiple infections by single-pathogen detection. This revealed a linear
      correlation for pathogens in children with ARTIs. This study provides useful
      information for improving case prevention and management. 

PMID- 25751404
TI  - BDNF-TrkB axis regulates migration of the lateral line primordium and modulates
      the maintenance of mechanoreceptor progenitors.
AB  - BDNF and its specialized receptor TrkB are expressed in the developing lateral
      line system of zebrafish, but their role in this organ is unknown. To tackle this
      problem in vivo, we used transgenic animals expressing fluorescent markers in
      different cell types of the lateral line and combined a BDNF gain-of-function
      approach by BDNF mRNA overexpression and by soaking embryos in a solution of
      BDNF, with a loss-of-function approach by injecting the antisence ntrk2b
      morpholino and treating embryos with the specific Trk inhibitor K252a. Subsequent
      analysis demonstrated that the BDNF-TrkB axis regulates migration of the lateral
      line primordium. In particular, BDNF-TrkB influences the expression level of
      components of chemokine signaling including Cxcr4b, and the generation of
      progenitors of mechanoreceptors, at the level of expression of Atoh1a-Atp2b1a. 

PMID- 25751405
TI  - Vascular plasticity and cognition during normal aging and dementia.

PMID- 25751400
TI  - Genome of The Netherlands population-specific imputations identify an ABCA6
      variant associated with cholesterol levels.
AB  - Variants associated with blood lipid levels may be population-specific. To
      identify low-frequency variants associated with this phenotype, population
      specific reference panels may be used. Here we impute nine large Dutch biobanks
      (~35,000 samples) with the population-specific reference panel created by the
      Genome of The Netherlands Project and perform association testing with blood
      lipid levels. We report the discovery of five novel associations at four loci (P
      value <6.61 * 10(-4)), including a rare missense variant in ABCA6 (rs77542162,
      p.Cys1359Arg, frequency 0.034), which is predicted to be deleterious. The
      frequency of this ABCA6 variant is 3.65-fold increased in the Dutch and its
      effect (betaLDL-C=0.135, betaTC=0.140) is estimated to be very similar to those
      observed for single variants in well-known lipid genes, such as LDLR.

PMID- 25751406
TI  - Dispersive and dissipative coupling in a micromechanical resonator embedded with
      a nanomechanical resonator.
AB  - A micromechanical resonator embedded with a nanomechanical resonator is developed
      whose dynamics can be captured by the coupled-Van der Pol-Duffing equations.
      Activating the nanomechanical resonator can dispersively shift the
      micromechanical resonance by more than 100 times its bandwidth and concurrently
      increase its energy dissipation rate to the point where it can even be
      deactivated. The coupled-Van der Pol-Duffing equations also suggest the
      possibility of self-oscillations. In the limit of strong excitation for the
      nanomechanical resonator, the dissipation in the micromechanical resonator can
      not only be reduced, resulting in a quality factor of >3* 10(6), it can even be
      eliminated entirely resulting in the micromechanical resonator spontaneously
      vibrating. 

PMID- 25751407
TI  - Metabolomics for phytochemical discovery: development of statistical approaches
      using a cranberry model system.
AB  - Metabolomics is the qualitative and quantitative analysis of all of the small
      molecules in a biological sample at a specific time and influence. Technologies
      for metabolomics analysis have developed rapidly as new analytical tools for
      chemical separations, mass spectrometry, and NMR spectroscopy have emerged.
      Plants have one of the largest metabolomes, and it is estimated that the average
      plant leaf can contain upward of 30 000 phytochemicals. In the past decade, over
      1200 papers on plant metabolomics have been published. A standard metabolomics
      data set contains vast amounts of information and can either investigate or
      generate hypotheses. The key factors in using plant metabolomics data most
      effectively are the experimental design, authentic standard availability, extract
      standardization, and statistical analysis. Using cranberry (Vaccinium
      macrocarpon) as a model system, this review will discuss and demonstrate
      strategies and tools for analysis and interpretation of metabolomics data sets
      including eliminating false discoveries and determining significance, metabolite
      clustering, and logical algorithms for discovery of new metabolites and pathways.
      Together these metabolomics tools represent an entirely new pipeline for
      phytochemical discovery. 

PMID- 25751408
TI  - Silver nanoparticle-based chemiluminescent sensor array for pesticide
      discrimination.
AB  - In this work, we developed a simple, facile, and highly sensitive nanoparticle
      based chemiluminescent (CL) sensor array for the discrimination of
      organophosphate and carbamate pesticides. This CL sensor array is based on
      simultaneous utilization of the triple-channel properties of the luminol
      functionalized silver nanoparticle (Lum-AgNP) and H2O2 CL system containing CL
      intensity, the time for CL emissions to appear, and the time to reach the CL peak
      value, which are able to be measured via a single experiment. The triple-channel
      properties can be simultaneously altered after interaction with pesticides,
      producing distinct CL response patterns as "fingerprints" related to each
      specific pesticide, which was subjected to principal component analysis (PCA) to
      generate a clustering map. Using this sensor array, five organophosphate and
      carbamate pesticides, including dimethoate, dipterex, carbaryl, chlorpyrifos, and
      carbofuran, have been well-distinguished at a concentration of 24 MUg/mL. A total
      of 20 unknown pesticide samples have been successfully identified with an
      accuracy of 95%. The simple strategy of this study is expected to promote the
      development of functionalized nanomaterial-based sensor arrays. 

PMID- 25751409
TI  - Matrix-assisted laser desorption/ionization mass spectrometric analysis of
      poly(3,4-ethylenedioxythiophene) in solid-state dye-sensitized solar cells:
      comparison of in situ photoelectrochemical polymerization in aqueous micellar and
      organic media.
AB  - Solid-state dye-sensitized solar cells (sDSCs) are devoid of such issues as
      electrolyte evaporation or leakage and electrode corrosion, which are typical for
      traditional liquid electrolyte-based DSCs. Poly(3,4-ethylenedioxythiophene)
      (PEDOT) is one of the most popular and efficient p-type conducting polymers that
      are used in sDSCs as a solid-state hole-transporting material. The most
      convenient way to deposit this insoluble polymer into the dye-sensitized
      mesoporous working electrode is in situ photoelectrochemical polymerization.
      Apparently, the structure and the physicochemical properties of the generated
      conducting polymer, which determine the photovoltaic performance of the
      corresponding solar cell, can be significantly affected by the preparation
      conditions. Therefore, a simple and fast analytical method that can reveal
      information on polymer chain length, possible chemical modifications, and
      impurities is strongly required for the rapid development of efficient solar
      energy-converting devices. In this contribution, we applied matrix-assisted laser
      desorption/ionization mass spectrometry (MALDI MS) for the analysis of PEDOT
      directly on sDSCs. It was found that the PEDOT generated in aqueous micellar
      medium possesses relatively shorter polymeric chains than the PEDOT deposited
      from an organic medium. Furthermore, the micellar electrolyte promotes a
      transformation of one of the thiophene terminal units to thiophenone. The
      introduction of a carbonyl group into the PEDOT molecule impedes the growth of
      the polymer chain and reduces the conductivity of the final polymer film. Both
      the simplicity of sample preparation (only application of the organic matrix onto
      the solar cell is needed) and the rapidity of analysis hold the promise of making
      MALDI MS an essential tool for the physicochemical characterization of conducting
      polymer-based sDSCs. 

PMID- 25751410
TI  - Erratum. Assessing approaches and barriers to reduce antipsychotic drug use in
      Florida nursing homes.

PMID- 25751411
TI  - Hopping versus Tunneling Mechanism for Long-Range Electron Transfer in Porphyrin
      Oligomer Bridged Donor-Acceptor Systems.
AB  - Achieving long-range charge transport in molecular systems is interesting to
      foresee applications of molecules in practical devices. However, designing
      molecular systems with pre-defined wire-like properties remains difficult due to
      the lack of understanding of the mechanism for charge transfer. Here we
      investigate a series of porphyrin oligomer-bridged donor-acceptor systems Fc-Pn
      C60 (n = 1-4, 6). In these triads, excitation of the porphyrin-based bridge
      generates the fully charge-separated state, Fc(*+)-Pn-C60(*-), through a sequence
      of electron transfer steps. Temperature dependence of both charge separation (Fc
      Pn*-C60 -> Fc-Pn(*+)-C60(*-)) and recombination (Fc(*+)-Pn-C60(*-) -> Fc-Pn-C60)
      processes was probed by time-resolved fluorescence and femtosecond transient
      absorption. In the long triads, two mechanisms contribute to recombination of
      Fc(*+)-Pn-C60(*-) to the ground state. At high temperatures (>=280 K),
      recombination via tunneling dominates for the entire series. At low temperatures
      (<280 K), unusual crossover from tunneling to hopping occurs in long triads. This
      crossover is rationalized by the increased lifetimes of Fc(*+)-Pn-C60(*-), hence
      the higher probability of reforming Fc-Pn(*+)-C60(*-) during recombination. We
      demonstrate that at 300 K, the weak distance dependence for charge transfer (beta
      = 0.028 A(-1)) relies on tunneling rather than hopping. 

PMID- 25751412
TI  - Demonstration of asymmetric electron conduction in pseudosymmetrical
      photosynthetic reaction centre proteins in an electrical circuit.
AB  - Photosynthetic reaction centres show promise for biomolecular electronics as
      nanoscale solar-powered batteries and molecular diodes that are amenable to
      atomic-level re-engineering. In this work the mechanism of electron conduction
      across the highly tractable Rhodobacter sphaeroides reaction centre is
      characterized by conductive atomic force microscopy. We find, using engineered
      proteins of known structure, that only one of the two cofactor wires connecting
      the positive and negative termini of this reaction centre is capable of
      conducting unidirectional current under a suitably oriented bias, irrespective of
      the magnitude of the bias or the applied force at the tunnelling junction. This
      behaviour, strong functional asymmetry in a largely symmetrical protein-cofactor
      matrix, recapitulates the strong functional asymmetry characteristic of natural
      photochemical charge separation, but it is surprising given that the stimulus for
      electron flow is simply an externally applied bias. Reasons for the electrical
      resistance displayed by the so-called B-wire of cofactors are explored. 

PMID- 25751414
TI  - Steroids in the equine oviduct: synthesis, local concentrations and receptor
      expression.
AB  - Steroids play an important role in mammalian reproduction and early pregnancy.
      Although systemic changes in steroid concentrations have been well documented, it
      is not clear how these correlate with local steroid concentrations in the genital
      tract. We hypothesised that, in the horse, the preimplantation embryo may be
      subjected to high local steroid concentrations for several days. Therefore, we
      measured progesterone, 17-hydroxyprogesterone, 17?-oestradiol, testosterone and
      17?-testosterone concentrations in equine oviductal tissue by ultra-HPLC coupled
      with tandem mass spectrometry, and progesterone, 17?-oestradiol, oestrone and
      testosterone concentrations in oviduct fluid by radioimmunoassay, with reference
      to cycle stage and side of ovulation. Progesterone concentrations were high in
      oviductal tissue and fluid ipsilateral to the ovulation side during dioestrus,
      whereas other steroid hormone concentrations were not influenced by the side of
      ovulation. These results suggest that the high ipsilateral progesterone
      concentration is caused by: (1) contributions from the follicular fluid in the
      oviduct and diffusion of follicular fluid steroids after ovulation; (2) local
      transfer of steroids via blood or lymph; (3) local synthesis of progesterone in
      the oviduct, as evidenced by the expression of steroidogenic enzymes; and (4) a
      paracrine contribution from follicular cells. These data provide a basis for the
      study of the importance of endocrine and paracrine signalling during early
      embryonic development in the horse.

PMID- 25751413
TI  - Mutational analysis of divalent metal ion binding in the active site of class II
      alpha-mannosidase from Sulfolobus solfataricus.
AB  - Mutational analysis of Sulfolobus solfataricus class II alpha-mannosidase was
      focused on side chains that interact with the hydroxyls of the -1 mannosyl of the
      substrate (Asp-534) or form ligands to the active site divalent metal ion (His
      228 and His-533) judged from crystal structures of homologous enzymes. D534A and
      D534N appeared to be completely inactive. When compared to the wild-type enzyme,
      the mutant enzymes in general showed only small changes in K(M) for the
      substrate, p-nitrophenyl-alpha-mannoside, but elevated activation constants,
      K(A), for the divalent metal ion (Co2+, Zn2+, Mn2+, or Cd2+). Some mutant enzyme
      forms displayed an altered preference for the metal ion compared to that of the
      wild type-enzyme. Furthermore, the H228Q, H533E, and H533Q enzymes were inhibited
      at increasing Zn2+ concentrations. The catalytic rate was reduced for all enzymes
      compared to that of the wild-type enzyme, although less dramatically with some
      activating metal ions. No major differences in the pH dependence between wild
      type and mutant enzymes were found in the presence of different metal ions. The
      pH optimum was 5, but enzyme instability was observed at pH <4.5; therefore, only
      the basic limb of the bell-shaped pH profile was analyzed.

PMID- 25751415
TI  - Highly effective configurational assignment using bisthioureas as chiral
      solvating agents in the presence of DABCO.
AB  - A highly effective (1)H NMR method for determining the absolute configurations of
      various chiral alpha-hydroxyl acids and their derivatives has been developed with
      the use of bisthioureas (R)-CSA 1 and (S)-CSA 1 as chiral solvating agents in the
      presence of DABCO, giving distinguishable proton signals with up to 0.66 ppm
      chemical shift nonequivalence. Computational modeling studies were performed with
      Gaussian09 to reveal the chiral recognition mechanism. 

PMID- 25751416
TI  - Profile development of noncommunicable chronic diseases in a Brazilian rural
      town.
AB  - OBJECTIVE: To assess the relationship between socioeconomic and anthropometric
      data, frequency of food consumption, and the development of noncommunicable
      diseases (NCDs) in patients from a small rural town in northeastern Brazil.
      METHODS: A cross-sectional questionnaire study was performed on patients from the
      Lagarto City Hospital (n = 50) and from family health units (n = 370). RESULTS:
      The 420 patients in the study had one or more NCDs such as hypertension, type 2
      diabetes mellitus, and dyslipidemia. The mean age was 63.1 +/- 8.7 years for both
      sexes. The typical patient was of mixed or black descent (66%), a farmer, and of
      low socioeconomic status and education; 100% of men and 84% of women were
      illiterate or had less than 4 years of schooling. Approximately 50% of women and
      89% of men were married and most had never used tobacco or were ex-smokers. The
      body mass index (BMI) of the study population was 29.4 +/- 5.5 kg/m(2), where 70%
      of the patients were type 2 diabetic with waist circumferences of 99.8 +/- 21.2
      cm for men and 98.1 +/- 13.9 cm for women. The correlation between BMI and waist
      circumference was r = 0.88. Even with the use of medication, total cholesterol
      levels of above 240 mg/dL were recorded in 10% of women and about 5% of men.
      Likewise, 10% of women and 100% of men had triglyceride levels above 200 mg/dL;
      glucose levels were 133.6 +/- 47.4 mg/dL in men and 110.8 +/- 38.8 mg/dL in
      women. Blood pressure values were high, even in patients using one or more
      antihypertensive drugs for at least 2 years (systolic pressure = 128.5 +/- 18.2;
      diastolic pressure = 86.3 +/- 8.9 mmHg). Indices considered above the limit
      recommended by the World Health Organization (WHO) were obtained for 60% of women
      and 100% of men. Our research revealed that this population is characterized by a
      relatively low intake of fats and oils. Nevertheless, 100% of patients consumed
      meat every day, 57.6% never consumed processed foods such as candy or soft
      drinks, and 89% consumed coffee daily. Furthermore, the consumption of fruits was
      very low: 46.6% of respondents never ate fruit and 7.8% rarely consumed fruit.
      Likewise, 68.2% reported never eating milk and dairy products. Vegetables were
      consumed by only 51.4% of the population and 38.5% rarely or never consumed green
      vegetables. Products made from wheat, maize, cassava, beans, and rice were often
      consumed by 59.2% of the population. CONCLUSIONS: Our results indicate that the
      studied population is affected by nutritional transition, in which the greater
      access to carbohydrates and animal proteins is associated with high BMI, with the
      vast majority overweight and suffering from uncontrolled hypertension despite the
      use of medications. The high consumption of carbohydrates and animal protein,
      rapid urbanization, and sedentary lifestyle are the main factors responsible for
      the epidemic of noncommunicable diseases, especially among people with low income
      and education. Men are particularly affected, with increased visceral fat
      characterized by an increased waist circumference.

PMID- 25751417
TI  - Measuring myocyte oxidative stress and targeting cytokines to evaluate
      inflammatory response and cardiac repair after myocardial infarction.

PMID- 25751419
TI  - Single layer graphene electrodes for quantum dot-light emitting diodes.
AB  - Single layer graphene was employed as the electrode in quantum dot-light emitting
      diodes (QD-LEDs) to replace indium tin oxide (ITO). The graphene layer
      demonstrated low surface roughness, good hole injection ability, and proper work
      function matching with the poly (3,4-ethylenedioxythiophene):poly
      (styrenesulfonate) layer. Together with the hole transport layer and electron
      transport layer, the fabricated QD-LED showed good current efficiency and power
      efficiency, which were even higher than an ITO-based similar device under low
      current density. The result indicates that graphene can be used as anodes to
      replace ITO in QD-LEDs. 

PMID- 25751420
TI  - Ab Initio Chemical Kinetics for the CH3 + O((3)P) Reaction and Related
      Isomerization-Decomposition of CH3O and CH2OH Radicals.
AB  - The kinetics and mechanism of the CH3 + O reaction and related isomerization
      decomposition of CH3O and CH2OH radicals have been studied by ab initio molecular
      orbital theory based on the CCSD(T)/aug-cc-pVTZ//CCSD/aug-cc-pVTZ, CCSD/aug-cc
      pVDZ, and G2M//B3LYP/6-311+G(3df,2p) levels of theory. The predicted potential
      energy surface of the CH3 + O reaction shows that the CHO + H2 products can be
      directly generated from CH3O by the TS3 -> LM1 -> TS7 -> LM2 -> TS4 path, in
      which both LM1 and LM2 are very loose and TS7 is roaming-like. The result for the
      CH2O + H reaction shows that there are three low-energy barrier processes
      including CH2O + H -> CHO + H2 via H-abstraction and CH2O + H -> CH2OH and CH2O +
      H -> CH3O by addition reactions. The predicted enthalpies of formation of the
      CH2OH and CH3O radicals at 0 K are in good agreement with available experimental
      data. Furthermore, the rate constants for the forward and some key reverse
      reactions have been predicted at 200-3000 K under various pressures. Based on the
      new reaction pathway for CH3 + O, the rate constants for the CH2O + H and CHO +
      H2 reactions were predicted with the microcanonical variational transition
      state/Rice-Ramsperger-Kassel-Marcus (VTST/RRKM) theory. The predicted total and
      individual product branching ratios (i.e., CO versus CH2O) are in good agreement
      with experimental data. The rate constant for the hydrogen abstraction reaction
      of CH2O + H has been calculated by the canonical variational transition-state
      theory with quantum tunneling and small-curvature corrections to be k(CH2O + H ->
      CHO + H2) = 2.28 * 10(-19) T(2.65) exp(-766.5/T) cm(3) molecule(-1) s(-1) for the
      200-3000 K temperature range. The rate constants for the addition giving CH3O and
      CH2OH and the decomposition of the two radicals have been calculated by the
      microcanonical RRKM theory with the time-dependent master equation solution of
      the multiple quantum well system in the 200-3000 K temperature range at 1 Torr to
      100 atm. The predicted rate constants are in good agreement with most of the
      available data. 

PMID- 25751422
TI  - Genetic determination of the hypothalamic-pituitary-thyroid axis: where do we
      stand?
AB  - For a long time it has been known that both hypo- and hyperthyroidism are
      associated with an increased risk of morbidity and mortality. In recent years, it
      has also become clear that minor variations in thyroid function, including
      subclinical dysfunction and variation in thyroid function within the reference
      range, can have important effects on clinical endpoints, such as bone mineral
      density, depression, metabolic syndrome, and cardiovascular mortality. Serum
      thyroid parameters show substantial interindividual variability, whereas the
      intraindividual variability lies within a narrow range. This suggests that every
      individual has a unique hypothalamus-pituitary-thyroid axis setpoint that is
      mainly determined by genetic factors, and this heritability has been estimated to
      be 40-60%. Various mutations in thyroid hormone pathway genes have been
      identified in persons with thyroid dysfunction or altered thyroid function tests.
      Because these causes are rare, many candidate gene and linkage studies have been
      performed over the years to identify more common variants (polymorphisms)
      associated with thyroid (dys)function, but only a limited number of consistent
      associations have been found. However, in the past 5 years, advances in genetic
      research have led to the identification of a large number of new candidate genes.
      In this review, we provide an overview of the current knowledge about the
      polygenic basis of thyroid (dys)function. This includes new candidate genes
      identified by genome-wide approaches, what insights these genes provide into the
      genetic basis of thyroid (dys)function, and which new techniques will help to
      further decipher the genetic basis of thyroid (dys)function in the near future. 

PMID- 25751421
TI  - Integrin alpha3beta1 signaling through MEK/ERK determines alternative
      polyadenylation of the MMP-9 mRNA transcript in immortalized mouse keratinocytes.
AB  - Integrin alpha3beta1 is highly expressed in both normal and tumorigenic epidermal
      keratinocytes where it regulates genes that control cellular function and
      extracellular matrix remodeling during normal and pathological tissue remodeling
      processes, including wound healing and development of squamous cell carcinoma
      (SCC). Previous studies identified a role for alpha3beta1 in immortalized and
      transformed keratinocytes in the regulation of genes that promote tumorigenesis,
      invasion, and pro-angiogenic crosstalk to endothelial cells. One such gene,
      matrix metalloproteinase-9 (MMP-9), is induced by alpha3beta1 through a post
      transcriptional mechanism of enhanced mRNA stability. In the current study, we
      sought to investigate the mechanism through which alpha3beta1 controls MMP-9 mRNA
      stability. First, we utilized a luciferase reporter assay to show that AU-rich
      elements (AREs) residing within the 3'-untranslated region (3'-UTR) of the MMP-9
      mRNA renders the transcript unstable in a manner that is independent of
      alpha3beta1. Next, we cloned a truncated variant of the MMP-9 mRNA which is
      generated through usage of an alternative, upstream polyadenylation signal and
      lacks the 3'-UTR region containing the destabilizing AREs. Using an RNase
      protection assay to distinguish "long" (full-length 3'-UTR) and "short"
      (truncated 3'-UTR) MMP-9 mRNA variants, we demonstrated that the shorter, more
      stable mRNA that lacks 3'-UTR AREs was preferentially generated in alpha3beta1
      expressing keratinocytes compared with alpha3beta1-deficient (i.e., alpha3-null)
      keratinocytes. Moreover, we determined that alpha3beta1-dependent alternative
      polyadenylation was acquired by immortalized keratinocytes, as primary neonatal
      keratinocytes did not display alpha3beta1-dependent differences in the long and
      short transcripts. Finally, pharmacological inhibition of the extracellular
      signal-regulated kinase (ERK)/mitogen-activated protein kinase (MAPK) pathway in
      alpha3beta1-expressing keratinocytes caused a shift towards long variant
      expression, while Raf-1-mediated activation of ERK in alpha3-null keratinocytes
      dramatically enhanced short variant expression, indicating a role for ERK/MAPK
      signaling in alpha3beta1-mediated selection of the proximal polyadenylation site.
      These findings identify a novel mode of integrin alpha3beta1-mediated gene
      regulation through alternative polyadenylation. 

PMID- 25751423
TI  - Safety of intravenous immunoglobulin and plasma exchange in critically ill
      patients.
AB  - OBJECTIVE: To assess the safety profile of intravenous immunoglobulin (IVIG) and
      plasma exchange (PLEX) when used to treat critically ill patients. METHODS: We
      performed a retrospective analysis of consecutive patients who received IVIG or
      PLEX while admitted to our medical intensive care unit (ICU), neuroscience ICU or
      haematologic/oncologic ICU between 2007 and 2011.Patients who were transferred
      into an ICU while receiving therapy or who continued therapy after discharge from
      the ICU were included in the analysis. RESULTS: A total of 118 consecutive
      patients were included in the study. Fifty-nine patients received IVIG. Twenty of
      these patients (34%) developed renal failure during the hospitalisation,
      including 15 (25.4%) in whom renal function worsened during or shortly after IVIG
      administration and 4 (6.8%) in whom IVIG was considered a possible cause.
      Transfusion reactions occurred in five patients (8%). Seven patients (12%) did
      not receive the full intended course of IVIG. Thirty-four patients (58%) who
      received IVIG died during their hospitalisation. Fifty-nine patients received
      PLEX. Hypotension requiring an intervention was noted with 39 sessions (8.5%) and
      led to discontinuation of the session in 11 (2.4%). Other adverse events included
      line-related infections (n = 4), pneumothorax (n = 4) and electrolyte
      abnormalities and transfusion reactions (n = 10). Six patients (10%) did not
      receive full intended treatment course of PLEX. Nineteen patients (32%) treated
      with PLEX died during their hospitalisation. DISCUSSION: Intravenous
      immunoglobulin and PLEX are generally well tolerated by critically ill patients.
      Intravenous immunoglobulin was associated with worsening renal function in one
      quarter of patients.

PMID- 25751424
TI  - NAD(+)-SIRT1 control of H3K4 trimethylation through circadian deacetylation of
      MLL1.
AB  - The circadian clock controls the transcription of hundreds of genes through
      specific chromatin-remodeling events. The histone methyltransferase mixed-lineage
      leukemia 1 (MLL1) coordinates recruitment of CLOCK-BMAL1 activator complexes to
      chromatin, an event associated with cyclic trimethylation of histone H3 Lys4
      (H3K4) at circadian promoters. Remarkably, in mouse liver circadian H3K4
      trimethylation is modulated by SIRT1, an NAD(+)-dependent deacetylase involved in
      clock control. We show that mammalian MLL1 is acetylated at two conserved
      residues, K1130 and K1133. Notably, MLL1 acetylation is cyclic, controlled by the
      clock and by SIRT1, and it affects the methyltransferase activity of MLL1.
      Moreover, H3K4 methylation at clock-controlled-gene promoters is influenced by
      pharmacological or genetic inactivation of SIRT1. Finally, levels of MLL1
      acetylation and H3K4 trimethylation at circadian gene promoters depend on NAD(+)
      circadian levels. These findings reveal a previously unappreciated regulatory
      pathway between energy metabolism and histone methylation. 

PMID- 25751425
TI  - Structural organization of the dynein-dynactin complex bound to microtubules.
AB  - Cytoplasmic dynein associates with dynactin to drive cargo movement on
      microtubules, but the structure of the dynein-dynactin complex is unknown. Using
      electron microscopy, we determined the organization of native bovine dynein,
      dynactin and the dynein-dynactin-microtubule quaternary complex. In the
      microtubule-bound complex, the dynein motor domains are positioned for processive
      unidirectional movement, and the cargo-binding domains of both dynein and
      dynactin are accessible. 

PMID- 25751427
TI  - Investigating the benefits of sport participation for individuals with
      schizophrenia: a systematic review.
AB  - BACKGROUND: The purpose of this review was to consider the impact of being
      introduced to a sport and sport participation on (a) weight loss and psychiatric
      symptoms, (b) any other health benefits in people with schizophrenia, supported
      by quantitative and qualitative findings. SUBJECT AND METHODS: A systematic
      review in accordance with the PRISMA statement was conducted. Searches were
      undertaken in January 2014. Articles were eligible that (1) considered the effect
      (quantitative studies) and experience (qualitative and case studies) of either;
      being introduced to a 'sport' or undertaking a sport activity, (2) included >85%
      of patients diagnosed with schizophrenia or schizo-affective spectrum disorders
      according to recognised criteria. RESULTS: A total of 10 studies including 5
      trials (2*pre-experimental, 2*controlled trials, 1*randomised control trial), 2
      qualitative studies and 3 case studies were included (n=185). Two out of 3
      studies that considered weight as an outcome measure reported significant
      reductions in weight and psychiatric symptoms following sports participation. The
      mean reduction in body mass index (BMI) ranged from -0.7kg.m2 (p<0.001) following
      12 weeks of basketball to -1.33 kg.m2 (p<0.001) after 12-weeks of soccer. The
      mean reduction in the Positive and Negative Symptoms score ranged from 2.4 points
      (F=-19.0, p<0.001) following 12 weeks of basketball to 7.4 points (t=-5.0,
      p<0.001) following a 40 week programme of horse riding. A range of secondary
      health and wellbeing outcomes identified some significant results. Qualitative
      findings showed that participants had positive experiences from participating in
      sports. CONCLUSIONS: Sport participation may result in reduced BMI and
      psychiatric symptoms in patients with schizophrenia. Sport has the potential to
      improve an individual's quality of life through providing a meaningful
      normalizing activity that leads to achievement, success and satisfaction. Well
      designed randomised controlled trials are required to fully determine the health
      effects of sports participation in schizophrenia.

PMID- 25751426
TI  - Evidence that processing of ribonucleotides in DNA by topoisomerase 1 is leading
      strand specific.
AB  - Ribonucleotides incorporated during DNA replication are removed by RNase H2
      dependent ribonucleotide excision repair (RER). In RER-defective yeast,
      topoisomerase 1 (Top1) incises DNA at unrepaired ribonucleotides, initiating
      their removal, but this is accompanied by RNA-DNA-damage phenotypes. Here we show
      that these phenotypes are incurred by a high level of ribonucleotides
      incorporated by a leading strand-replicase variant, DNA polymerase (Pol) E, but
      not by orthologous variants of the lagging-strand replicases, Pols alpha or
      delta. Moreover, loss of both RNases H1 and H2 is lethal in combination with
      increased ribonucleotide incorporation by Pol E but not by Pols alpha or delta.
      Several explanations for this asymmetry are considered, including the idea that
      Top1 incision at ribonucleotides relieves torsional stress in the nascent leading
      strand but not in the nascent lagging strand, in which preexisting nicks prevent
      the accumulation of superhelical tension. 

PMID- 25751428
TI  - Neurotransmitter measures in the cerebrospinal fluid of patients with Alzheimer's
      disease: a review.
AB  - BACKGROUND: Alzheimer's disease (AD) is a severe neurodegenerative disorder
      characterized by progressive cognitive and functional decline, as well as by a
      variety of neuropsychiatric and psychological symptoms and behavioral
      dysfunctions. Various studies proposed the role of different neurotransmitter
      systems not only in AD-related cognitive, but also psychotic symptoms and
      behavioral and emotional deficits. Due to the close proximity, pathological
      neurochemical changes in brain occurring in AD are likely to be reflected in the
      cerebrospinal fluid (CSF). The purpose of this review is to provide a summary of
      the CSF neurotransmitter correlates of AD in order to get further insights into
      the potential role of altered neurotransmitters in the pathophysiology of AD and
      to offer novel AD biomarkers. METHODS: PubMed and MEDLINE data bases were
      searched for English-language articles by using "Alzheimer's disease", "CSF" and
      "neurotransmitter" as primary terms. No time or article type constraints were
      applied. Moreover, the lists of references were searched manually for additional
      articles. RESULTS: Changes in various correlates of cholinergic, monoaminergic
      and amino acid neurotransmitter systems, as well as neuropeptides, have been
      observed in CSF of AD patients. However, as the results of these studies have
      been controversial, the importance of CSF neurotransmitter parameters as
      potential biomarkers in AD remains quite unclear. The observed discrepancies
      could be bypassed by implementation of new sensitive methods, such as novel
      proteomics approaches that include protein separation techniques, mass
      spectroscopy and targeted multiplex panels of specific analytes. CONCLUSION:
      Although no individual CSF neurotransmitter correlate was demonstrated as
      suitable biomarker of AD, a combined profile of several CSF neurochemical
      parameters might show enhanced sensitivity and specificity and thus contribute to
      earlier and more accurate diagnosis of AD, crucial for application of effective
      treatments.

PMID- 25751429
TI  - Prevalence of depression symptoms and associated socio-demographic factors in
      primary health care patients.
AB  - BACKGROUND: Depression is a growing public health problem still under-recognised
      in primary care settings. By focusing primarily on somatic complaints and
      diseases, general practitioners often fail to identify an underlying mental
      disorder. The aim of this study was to assess the prevalence of patients with
      unrecognised depression symptoms in general practice and identify associated
      socio-demographic factors. SUBJECTS AND METHODS: The study included 769 patients
      without previous psychiatric disorder who attended their primary care physicians
      in the Health Centre Zagreb - Zapad in January 2011. Data on patients' age, sex,
      level of education, marital and employment status were collected. All
      participants completed The Zung Self-Rating Depression Scale. RESULTS: Among the
      25.5% of participants whose Zung score was outside the normal range, 19.38% were
      mildly, 4.64% moderately, and 0.91% severely depressed. Statistically significant
      differences were observed among groups defined according to level of education,
      employment and marital status (p<0.001). Lower Zung scores were found in
      individuals with a higher level of education, who were unmarried, employed or
      still undergoing education. Multivariate logistic regression model revealed that
      older age (p<0.001), unemployment (p=0.001) or unmarried status (p=0.025) were
      significant predictors of depression symptoms. CONCLUSIONS: The study revealed a
      high prevalence of depression symptoms among primary care patients who had not
      been previously suspected to have any psychiatric co-morbidity. Awareness of
      depression symptoms and disorders should be raised among general practitioners,
      focusing on older, unemployed and unmarried people.

PMID- 25751430
TI  - Cognitive functions in first-episode depression and recurrent depressive
      disorder.
AB  - BACKGROUND: Cognitive deficits in the course of depressive disorders affect
      mainly memory, attention and the frontal functions. They are associated with both
      an earlier onset of symptoms and prolonged episodes. The main aim of the study
      was to verify the hypothesis of differences in the effectiveness of cognitive
      processes between patients with a first episode of depression (ED-I) and
      recurrent depressive disorders (rDD). SUBJECTS AND METHODS: The study comprised
      210 subjects: patients with ED-I (n=60) and patients with rDD (n=150). The
      assessment of cognitive functions was based on performance of the Trail Making
      Test, the Stroop Test, the Verbal Fluency Test, the California Verbal Learning
      Test (CVLT) and the digit span from WAIS-R. RESULTS: There were no statistically
      significant differences between the analysed groups in the severity of depressive
      symptoms. The negative impact of depressive symptoms on the effectiveness of
      cognitive functions was observed. The ED-I group recorded better results compared
      to the rDD group in terms of the speed of information processing, visual-spatial
      and auditory-verbal memory and executive functions, auditory-verbal immediate and
      delayed memory, ability to learn and verbal fluency. The same differences were
      observed with respect to the patients from the ED-I group and the patients with
      the second episode of depression (ED-II) in the course of rDD. CONCLUSIONS: There
      are significant differences in cognitive functioning of patients with a
      depressive episode and recurrent depressive disorders. These differences are
      already visible from the second episode of a major depressive disorder. Memory,
      verbal fluency and frontal functions are reduced.

PMID- 25751431
TI  - Beyond childhood: psychiatric comorbidities and social background of adults with
      Asperger syndrome.
AB  - BACKGROUND: Over the past few years, our knowledge about Asperger syndrome (AS)
      has increased enormously. Although it used to be a syndrome mainly encountered in
      childhood and adolescent psychiatry, it is now increasingly recognized in adult
      psychiatry. Nevertheless, little is known about psychiatric comorbidities and
      life course of adults with AS. The current study aimed to gain an insight into
      comorbidities and the development of the social situation of adults with AS.
      SUBJECTS AND METHODS: We investigated psychiatric comorbidities, psychiatric
      history, professional background, partnerships, and children in 50 adults with AS
      (34 men and 16 women) over a broad age range (20-62 years). RESULTS: Seventy
      percent of adults with AS had at least one psychiatric comorbiditiy. Most
      frequent comorbidities were depression and anxiety disorders. Obsessive
      compulsive disorder and alcohol abuse/dependence were also observed. Many adults
      had previously been treated with psychopharmacological or psychotherapeutic
      interventions. Although most adults had a high-level school leaving certificate
      and had gone on to complete training/university studies, less than half were
      currently in employment. Fourteen adults were living in a partnership and 10 had
      children. CONCLUSIONS: Adults with AS often have psychiatric comorbidities,
      indicating lower levels of mental health. Additionally, they seem to have severe
      limitations concerning professional success, despite having a good school
      education. Their family situation is also impaired with regard to starting a
      family. These considerable limitations in the life of adults with AS may help to
      understand their specific problems, and emphasize the importance of developing
      specific treatments for improving their mental health and social integration.

PMID- 25751432
TI  - Temperament, character, and suicidality among Croatian war veterans with
      posttraumatic stress disorder.
AB  - BACKGROUND: The occurrence of suicidal thoughts and behaviors is rather frequent
      among war veterans, particularly those suffering from posttraumatic stress
      disorder (PTSD). Understanding factors present within these individuals that
      increase suicide risk may inform prevention efforts. The present study aimed to
      determine whether the dimensions of temperament and character are associated with
      various aspects of suicidality among Croatian war veterans with PTSD. SUBJECTS
      AND METHODS: A sample of 72 Croatian male war veterans (mean age 52.33 years)
      diagnosed with PTSD was gathered at the National Center for Psychotrauma between
      May and October 2014. The participants completed the Temperament and Character
      Inventory - Revised (TCI-R) and the Suicidal Behaviors Questionnaire - Revised
      (SBQ-R). RESULTS: Zero-order analyses revealed that temperament dimension Harm
      avoidance and character dimension Self-directedness were moderately associated
      with the total risk for suicide (i.e., the SBQ-R total score), while Persistence
      and Cooperativeness showed significant but weaker relations. Different dimensions
      of suicidality were associated with different personality traits. Harm Avoidance
      was shown to be significantly increased among the subgroup of war veterans with
      high suicidal risk. CONCLUSIONS: Notwithstanding some limitations of this study,
      these findings could help extend our understanding of the elevated suicide risk
      in war veterans with PTSD. Detection of individuals displaying high Harm
      Avoidance and low Self-Directedness might facilitate prevention of suicidal
      behaviors in this population.

PMID- 25751433
TI  - Challenges in the management of delirium: a case of augmentation with donepezil
      following inadequate response and adverse effects with risperidone.

PMID- 25751434
TI  - Are reduplicative paramnesia and clonal pluralization overlapping constructs?

PMID- 25751435
TI  - Commentary on ''Quantitative electroencephalography in schizophrenia and
      depression''.

PMID- 25751436
TI  - PAI-1 as a component of the metabolic syndrome in depression and schizophrenia -
      Croatian experience.

PMID- 25751437
TI  - "Polysomnographic" and "sleep" patterns: synonims or two distinct terms.

PMID- 25751438
TI  - "Polysomnographic" and "sleep" patterns: synonims or two distinct terms - a
      reply.

PMID- 25751439
TI  - The relation between neutrophil-lymphocyte ratio and schizophrenia: commentary on
      Semiz et al. (2014).

PMID- 25751440
TI  - Brain changes in patients with posttraumatic stress disorder and associated
      alcoholism: MRI based study.
AB  - BACKGROUND: Studies imposing rigorous control over lifetime alcohol intake
      usually have not found smaller hippocampal volumes in persons with posttraumatic
      stress disorder (PTSD). Since the majority of negative studies have used
      adolescent samples, it has been suggested that chronicity is a necessary
      condition for such findings. We have hypothesized that the volumes of
      hippocampus, amygdale, prefrontal cortex and the intracranial volume are reduced
      in the patients with PTSD and excessive alcohol intake. SUBJECTS AND METHODS:
      Study has been carried out on 54 therapy naive PTSD suffering subjects and
      healthy controls, divided in two groups: 29 with PTSD and consequent alcoholism,
      25 with PTSD but without problems of excessive alcohol intake, and 25 healthy
      volunteers. All of the patients underwent same magnetic resonance imaging (MRI)
      protocol and volumetric evaluation of the region of interest. RESULTS: Only
      hippocampal volume appeared to be significantly reduced in patients with PTSD and
      alcoholism. Other differences in the volumes obtained remained to be
      insignificant. CONCLUSION: Alcohol intake definitely worsens the deterioration of
      the hippocampal formation in PTSD suffering patients. Nevertheless, other
      structures of interest for this study did not manifest any kind of statistical
      differences in volumetric analysis.

PMID- 25751441
TI  - Comorbidity of harmful use of alcohol in population of schizophrenic patients.
AB  - BACKGROUND: Numerous studies carried out during the last twenty years point to an
      increase of co-morbidity of harmful use of alcohole caused disorders in the
      population of schizophrenic patients. The results show rate of this kind of co
      morbidity between 35 and 80%. The aims of the investigation are: establishing
      frequency of harmful use of alcohol in the patients with diagnosis of
      schizophrenia, observed against the population statistics data; determination of
      possible predictors of harmful use of alcohol in the population of schizophrenic
      patients (adolsecent bihevioural problems, child neuroticism); determination of
      heritage role in the development of the both nosologic entities and the analysis
      of the outcomes of harmful use of alcohol in the population of schizophrenic
      patients (suicide attempts, cognitive impairment). SUBJECTS AND METHODS: The
      population included 50 inpatients between 20 and 50 years, with primary diagnosis
      of schizophrenia. Diagnostic procedure was carried out by application: Structured
      clinical interview ICD 10 (Mini International Neuropsychiatric Interview),
      Structured questionnaire for the assessment characteristics and effects of
      harmful use of alcohol in the population of schizophrenics - modified version,
      Mini mental state scale and Heteroanamnestic questionnaire. Comparison was made
      between the patients with schizophrenia and the patients with co-morbidity.
      RESULTS: The results revealed significantly higher rate harmful use of alcohol co
      morbidity in the male population. There is a prominent significant difference in
      alcoholism heritage in co-morbidity group. A statistically significant difference
      between the sub-groups was found in the frequency of child neuroticism and
      adolescent behavioral problems. The results point to a higher suicidal risk and
      higher rate of cognitive impairment in the co-morbidity sub-group. CONCLUSIONS:
      Young male with schizophrenia and family history of alcoholism are especially
      susceptible by this type of co-morbidity. Presence of child neuroticism may
      represent "protective factor" for development of harmful use of alcohol. The
      study stressed some serious consequences of this type of co-morbidity: increase
      rate of suicide attempts, as well as more frequent development of organic brain
      tissue impairment.

PMID- 25751442
TI  - Alcoholic and postoperative delirium: a case-control study.
AB  - BACKGROUND: Delirium is an urgent condition in psychiatry and it occurs after
      long-lasting alcohol abuse, in surgical procedures and other organic mental
      syndromes with deprivation of interpersonal and social stimulations. The aim was
      to evaluate of sociodemographical and psychopathological differences in delirium
      patients with alcoholand surgical genesis, studied in period from January 1(st)
      2003 to December 31(st) 2012 in Bosnia and Herzegovina (B&H). SUBJECTS AND
      METHODS: Subjects were divided into two groups: alcoholics (N=75) and surgical
      patients (N=75) and multicentric, prospective study was performed in B&H. The
      following instruments have been used: list of general data (according to MCD-10
      criteria), Eysenck Personality Questionnaire (EPQ), Becks test of anxiety (BAI),
      Hamilton Depressive Rating Scale (HDRS) and Mini Mental State Examination (MMSE).
      Descriptive and analytical statistical processing of patients has been performed
      (alpha level: 0.001). RESULTS: Patients from alcohol group showed, with
      statistical significance p=0.001, the following: unemployment (OR=0.657, CI 0.540
      670), ruined marriage (OR=0.570, CI 0.650-710), alcohol abuse (OR=0.179, CI 0.860
      0.990), on represented expressed psychoticism, (OR=0.635, CI 0.550-0.715) in EPQ
      test, HDRS total was more frequent (OR=0.925, CI 0.870-1.120) and on MMSE test,
      total score was more frequent (OR=0.560, CI 0.570-810). Postoperative patients
      were older p=0.001 (OR=1.120, CI 1.082-1.159) with acutestress: (OR=0.735, CI
      0.650-0.910) and showed neuroticism (OR=-0.660, CI 0.575-0.715). Discriminative
      function confirms the differences between alcohol and surgical groups of delirium
      patients: Canonical Fcn: r=0.771; Wilkin's lambda (lambdanj)=0.773 Student's
      test=57.551 and significance p=0.001; OR=0.760, CI 0.550-0.870. CONCLUSION:
      Delirium lasts longer in alcohol group with higher disalienation, depression of
      cognitive functions with organic lesions of cerebral functions. In surgical
      patients, delirium is the consequence of older age, acute stress, multi
      morbidity, with neuroticism, vegetative disorders (HDRS) and temporary lesion on
      MMSE test. Delirium state in both groups requires intensive care and
      multidisciplinary work.

PMID- 25751443
TI  - Cannabis and psychosis revisited.
AB  - The association between cannabinoids and psychosis has been known for almost a
      thousand years, but it is still speculated whether cannabis use may be a
      contributory cause of psychosis, that is, whether it may precipitate
      schizophrenia in those at risk. In this paper, we will briefly present the data
      from individual longitudinal studies in the field, together with the factors that
      are considered important for the association of cannabis abuse and occurrence of
      schizophrenia and prevention opportunities in the target population. The reviewed
      studies clearly suggest that cannabis abuse predicts an increased risk for
      schizophrenia, particularly in young adults. They underline both the need to
      create adequate prevention measures and consequently avoid the occurrence of the
      disease in the young at risk. Particular attention should be additionally devoted
      toward encouraging the young presenting with psychotic symptoms to stop or, at
      the very least, reduce the frequency of cannabis abuse. The issues are
      undoubtedly to be addressed by the health care system in general. 

PMID- 25751444
TI  - Food addiction-diagnosis and treatment.
AB  - In this article we summarized the recent research of the food addiction,
      diagnosis, treatment and prevention, which is carried out in this area. The
      concept of food addiction is new and complex, but proven to be very important for
      understanding and solving the problem of obesity. First part of this paper
      emphasizes the neurological studies, whose results indicate the similarity of
      brain processes that are being activated during drug abuse and during eating
      certain types of food. In this context, different authors speak of "hyper
      palatable", industrial food, saturated with salt, fat and sugar, which favor an
      addiction. In the section on diagnostic and instruments constructed for assessing
      the degree of dependence, main diagnostic tool is standardized Yale Food
      Addiction Scale constructed by Ashley Gearhardt, and her associates. Since 2009,
      when it was first published, this scale is used in almost all researches in this
      area and has been translated into several languages. Finally, distinguish between
      prevention and treatment of food addiction was made. Given that there were
      similarities with other forms of addictive behavior, the researchers recommend
      the application of traditional addiction treatment. 

PMID- 25751445
TI  - Treatment of pathological gambling - integrative systemic model.
AB  - Pathological gambling was classified under impulse control disorders within the
      International Classification of Diseases (ICD-10) (WHO 1992), but the most recent
      Diagnostic and Statistical Manual, 5th edition (DSM-V), (APA 2013), has
      recognized pathological gambling as a first disorder within a new diagnostic
      category of behavioral addictions - Gambling disorder. Pathological gambling is a
      disorder in progression, and we hope that our experience in the treatment of
      pathological gambling in the Daily Hospital for Addictions at The Institute of
      Mental Health, through the original "Integrative - systemic model" would be of
      use to colleagues, dealing with this pathology. This model of treatment of
      pathological gambling is based on multi-systemic approach and it primarily
      represents an integration of family and cognitive-behavioral therapy, with traces
      of psychodynamic, existential and pharmacotherapy. The model is based on the book
      "Pathological gambling - with self-help manual" by Dr Mladenovic and Dr Lazetic,
      and has been designed in the form of a program that lasts 10 weeks in the
      intensive phase, and then continues for two years in the form of "extended
      treatment" ("After care"). The intensive phase is divided into three segments:
      educational, insight with initial changes and analysis of the achieved changes
      with the definition of plans and areas that need to be addressed in the extended
      treatment. "Extended treatment" lasts for two years in the form of group therapy,
      during which there is a second order change of the identified patient, but also
      of other family members. Pathological gambling has been treated in the form of
      systemic-family therapy for more than 10 years at the Institute of Mental Health
      (IMH), in Belgrade. For second year in a row the treatment is carried out by the
      modern "Integrative-systemic model". If abstinence from gambling witihin the
      period of one year after completion of the intensive phase of treatment is taken
      as the main criterion of the effectiveness of our model, at this time it exceeds
      90%. Given the relatively short period of application, it is necessary to
      continue to monitor and evaluate the model after 5 years. 

PMID- 25751446
TI  - Urinary neopterine levels in patients with major depressive disorder: alterations
      after treatment with paroxetine and comparison with healthy controls.
AB  - BACKGROUND: A close relationship has been shown between mood disorders and
      pteridine levels. The aim of this study was to examine alterations in the urine
      neopterine levels of patients with major depressive disorder (MDD) who responded
      to paroxetine during the initial treatment and to compare their levels to those
      of healthy controls. SUBJECTS AND METHODS: Sixteen patients with major depression
      and 19 healthy controls were enrolled in the study. In order to assess depression
      severity levels, the Beck Depression Inventory, the Beck Anxiety Inventory, and
      the State-Trait Anxiety Inventory were administered. Urinary neopterine values
      that were measured using high pressure liquid chromatography (HPLC) were compared
      using non-parametric tests for the MDD patients before and after treatment. Urine
      neopterine levels in MDD patients before and after treatment were compared to
      those of the healthy control group. RESULTS: Urinary neopterine levels were
      recorded as follows: For the MDD group before treatment the mean level was
      187.92+/-54.79 MUmol/creatinine. The same group under treatment at 4 to 8 weeks
      was at 188.53+/-4962 MUmol/creatinine, and the healthy control group showed
      150.57+/-152.98 MUmol/creatinine levels. There was no statistically significant
      difference in the urinary neopterine levels among the MDD patients before and
      after treatment (p=0.938). When urine neopterine levels in MDD patients before
      and after treatment were compared to those of the healthy control group, levels
      in the MDD group were found to be significantly higher (p=0.004 and p=0.005,
      respectively). CONCLUSIONS: Findings from the current study suggest that despite
      treatment response, depression is related to higher levels of urine neopterine.
      Paroxetine treatment has no significant effect on urine levels of neopterine in
      MDD patients.

PMID- 25751447
TI  - Effects of massage on the anxiety of patients receiving percutaneous coronary
      intervention.
AB  - BACKGROUND: This study aimed to explore the effects of massage on the state
      anxiety of patients receiving percutaneous coronary intervention (PCI). SUBJECTS
      AND METHODS: In accordance with the principle of the minimum allocation of
      imbalance index for comparability, a total of 117 cases that were ready to
      receive PCI were divided into two groups (59 in the intervention group and 58 in
      the control group). The patients in the control group received routine care,
      whereas the patients in the observation group were given massage intervention.
      The state anxiety, heart rate, and blood pressure of the two groups were observed
      and compared. RESULTS: Massage treatments reduced the emergency response and
      level of anxiety of cardiovascular patients before PCI. The post-intervention
      blood pressure, heart rate, and pain score of the intervention group were
      significantly better than those of the control group (P<0.05). CONCLUSIONS:
      Health professionals should pay attention to and strengthen the exploration of
      the effects of reasonable care intervention mode under PCI to promote the
      physical and mental health of patients, as well as improve their medical care
      satisfaction.

PMID- 25751448
TI  - Incipient charge order observed by NMR in the normal state of YBa2Cu3Oy.
AB  - The pseudogap regime of high-temperature cuprates harbours diverse manifestations
      of electronic ordering whose exact nature and universality remain debated. Here,
      we show that the short-ranged charge order recently reported in the normal state
      of YBa2Cu3Oy corresponds to a truly static modulation of the charge density. We
      also show that this modulation impacts on most electronic properties, that it
      appears jointly with intra-unit-cell nematic, but not magnetic, order, and that
      it exhibits differences with the charge density wave observed at lower
      temperatures in high magnetic fields. These observations prove mostly universal,
      they place new constraints on the origin of the charge density wave and they
      reveal that the charge modulation is pinned by native defects. Similarities with
      results in layered metals such as NbSe2, in which defects nucleate halos of
      incipient charge density wave at temperatures above the ordering transition,
      raise the possibility that order-parameter fluctuations, but no static order,
      would be observed in the normal state of most cuprates if disorder were absent. 

PMID- 25751449
TI  - Medicago truncatula Mtha1-2 mutants loose metabolic responses to mycorrhizal
      colonization.
AB  - Bidirectional nutrient transfer is one of the key features of the arbuscular
      mycorrhizal symbiosis. Recently we were able to identify a Medicago truncatula
      mutant (mtha1-2) that is defective in the uptake of phosphate from the
      periarbuscular space due to a lack of the energy providing proton gradient
      provided by the symbiosis specific proton ATPase MtHA1 In order to further
      characterize the impact of fungal colonization on the plant metabolic status,
      without the beneficial aspect of improved mineral nutrition, we performed leaf
      ion analyses in mutant and wildtype plants with and without fungal colonization.
      Although frequency of fungal colonization was unaltered, the mutant did not show
      a positive growth response to mycorrhizal colonization. This indicates that
      nutrient transfer into the plant cell fails in the truncated arbuscules due to
      lacking expression of a functional MtHA1 protein. The leaves of wildtype plants
      showed clear metabolic responses to root mycorrhizal colonization, whereas no
      changes of leaf metabolite levels of mycorrhizal mtha1-2 plants were detected,
      even though they were colonized. These results show that MtHa1 is indispensable
      for a functional mycorrhizal symbiosis and, moreover, suggest that fungal root
      colonization per se does not depend on nutrient transfer to the plant host.

PMID- 25751451
TI  - Client and therapist agreement about the client's problems-Associations with
      treatment alliance and outcome.
AB  - OBJECTIVE: A shared understanding of the patient's symptoms and problems is seen
      by most theories as a crucial aspect of the collaboration in therapy, presumably
      influencing alliance and outcome. The empirical ground for this argument is not
      solid, however. Several studies have found weak associations between a common
      view of the patient's problems and outcome. The purpose of the present study was
      to analyze whether agreement in the understanding of the patient's depression and
      anxiety problems was important for alliance and outcome. METHOD: The study used
      data from a practice-based study using the CORE system with 846 patients who
      received psychological treatment in primary care. RESULTS: The analyses indicated
      that although patients who were assessed by their therapists as having depression
      and anxiety problems scored higher on these subscales than other patients, about
      half of the patients reported such problems when the therapists did not, and vice
      versa. Agreement was not associated with better alliance or outcome. CONCLUSIONS:
      Productive collaboration in psychotherapy may be based on other factors than
      agreement about symptoms.

PMID- 25751452
TI  - A three-dimensional ankle kinetostatic model to simulate loaded and unloaded
      joint motion.
AB  - A kinetostatic model able to replicate both the natural unloaded motion of the
      tibiotalar (or ankle) joint and the joint behavior under external loads is
      presented. The model is developed as the second step of a sequential procedure,
      which allows the definition of a kinetostatic model as a generalization of a
      kinematic model of the joint defined at the first step. Specifically, this
      kinematic model taken as the starting point of the definition procedure is a
      parallel spatial mechanism which replicates the ankle unloaded motion. It
      features two rigid bodies (representing the tibia-fibula and the talus-calcaneus
      complexes) interconnected by five rigid binary links, that mimic three articular
      contacts and two nearly isometric fibers (IFs) of the tibiocalcaneal ligament
      (TiCaL) and calcaneofibular ligament (CaFiL). In the kinetostatic model, the five
      links are considered as compliant; moreover, further elastic structures are added
      to represent all the main ankle passive structures of the joint. Thanks to this
      definition procedure, the kinetostatic model still replicates the ankle unloaded
      motion with the same accuracy as the kinematic model. In addition, the model can
      replicate the behavior of the joint when external loads are applied. Finally, the
      structures that guide these motions are consistent with the anatomical evidence.
      The parameters of the model are identified for two specimens from both subject
      specific and published data. Loads are then applied to the model in order to
      simulate two common clinical tests. The model-predicted ankle motion shows good
      agreement with results from the literature. 

PMID- 25751453
TI  - Intimate partner violence and communication of HIV diagnosis in Rakai, Uganda.
AB  - Individuals who communicate their HIV diagnosis to sexual partners may be at
      increased risk of intimate partner violence (IPV). The authors examined past year
      self-reported IPV associated with communication of HIV diagnosis and other
      factors, in a sample of 679 sexually active; HIV-positive individuals age 18 to
      49, who received HIV results and posttest counselling 12 months or more prior to
      the survey in Rakai, Uganda, using log-binomial multivariable regression. The
      rates of verbal and physical abuse among married individuals were significantly
      higher compared to unmarried persons, respectively. Physical abuse was
      significantly higher among women compared to men. IPV was not significantly
      associated with communication of HIV diagnosis. Interventions to prevent IPV
      among married HIV-positive individuals particularly women, at the community
      level, are needed. 

PMID- 25751455
TI  - Interactions between nodes in a physical gel network of telechelic polymers; self
      consistent field calculations beyond the cell model.
AB  - Triblock copolymers, with associative end-groups and a soluble middle block, form
      flower-like micelles in dilute solutions and a physical gel at higher
      concentrations. In a gel the middle blocks form bridges between domains/nodes
      that contain the ends. We combine the self-consistent field theory with a simple
      molecular model to evaluate the pair potential between the nodes. In this model
      the end-groups are forced to remain in nodes and the soluble middle blocks are in
      solution. When the distance between the centres of the nodes is approximately the
      corona diameter, loops can transform into bridges, and the pair potential is
      attractive. Due to steric hindrance, the interaction is repulsive at smaller
      distances. Till now a cell-model has been used wherein a central node interacts
      through reflecting boundary conditions with its images in a spherical geometry.
      This artificial approach to estimate pair potentials is here complemented by more
      realistic three-gradient SCF models. We consider the pair interactions for (i)
      two isolated nodes, (ii) nodes positioned on a line (iii) a central node
      surrounded by its neighbours in simple cubic ordering, and (iv) a central node in
      a face centred cubic configuration of its neighbours. Qualitatively, the cell
      model is in line with the more refined models, but quantitative differences are
      significant. We also notice qualitative differences for the pair potentials in
      the specified geometries, which we interpret as a breakdown of the pairwise
      additivity of the pair potential. This implies that for course grained Monte
      Carlo or molecular dynamics simulations the best choice for the pair potentials
      depends on the expected node density. 

PMID- 25751457
TI  - Food quantity affects the sensitivity of Daphnia to road salt.
AB  - Road deicing operations have raised chloride (Cl) levels in many temperate lakes
      in Europe and North America. These lakes vary widely in trophic status, but to
      date, no one has quantified the interaction between food quantity and road salt
      toxicity. We examined the effects of food quantity (particulate algal C
      concentration (C)) on the chronic toxicity of Cl to Daphnia in soft-water
      bioassays. There was a strong positive linear relationship (r(2) = 0.92 for NaCl
      and r(2) = 0.96 for CaCl2) between food quantity and Cl LC50. As food quantity
      increased from 0.2 to 1.0 mg C/L (levels characteristic of oligotrophic to
      eutrophic lakes, respectively), the chronic Cl LC50 increased from 55.7 to 284.8
      mg Cl/L. Salt type (NaCl or CaCl2) did not affect the Cl LC50, Daphnia life
      history parameters, or the intrinsic rate of population increase (r). The life
      history parameter most sensitive to Cl was neonate production. Cl did not inhibit
      egg production, nor was the maternal lipid investment in eggs changed, but egg
      viability and the subsequent release of live neonates decreased as Cl levels
      increased and food decreased. Our results suggest the trophic status of lakes
      should be considered when assessing ecological threat from Cl. 

PMID- 25751456
TI  - Effects of age and diabetes on scleral stiffness.
AB  - The effects of diabetes on the collagen structure and material properties of the
      sclera are unknown but may be important to elucidate whether diabetes is a risk
      factor for major ocular diseases such as glaucoma. This study provides a
      quantitative assessment of the changes in scleral stiffness and collagen fiber
      alignment associated with diabetes. Posterior scleral shells from five diabetic
      donors and seven non-diabetic donors were pressurized to 30 mm Hg. Three
      dimensional surface displacements were calculated during inflation testing using
      digital image correlation (DIC). After testing, each specimen was subjected to
      wide-angle X-ray scattering (WAXS) measurements of its collagen organization.
      Specimen-specific finite element models of the posterior scleras were generated
      from the experimentally measured geometry. An inverse finite element analysis was
      developed to determine the material properties of the specimens, i.e., matrix and
      fiber stiffness, by matching DIC-measured and finite element predicted
      displacement fields. Effects of age and diabetes on the degree of fiber
      alignment, matrix and collagen fiber stiffness, and mechanical anisotropy were
      estimated using mixed effects models accounting for spatial autocorrelation.
      Older age was associated with a lower degree of fiber alignment and larger matrix
      stiffness for both diabetic and non-diabetic scleras. However, the age-related
      increase in matrix stiffness was 87% larger in diabetic specimens compared to non
      diabetic controls and diabetic scleras had a significantly larger matrix
      stiffness (p = 0.01). Older age was associated with a nearly significant increase
      in collagen fiber stiffness for diabetic specimens only (p = 0.06), as well as a
      decrease in mechanical anisotropy for non-diabetic scleras only (p = 0.04). The
      interaction between age and diabetes was not significant for all outcomes. This
      study suggests that the age-related increase in scleral stiffness is accelerated
      in eyes with diabetes, which may have important implications in glaucoma. 

PMID- 25751458
TI  - Congenital Disseminated Extrarenal Malignant Rhabdoid Tumor.
AB  - Soft tissue tumors arising in association with genetic or malformation syndromes
      have been increasingly reported. Malignant rhabdoid tumor (MRT) is a highly
      aggressive neoplasm of infancy and young childhood, characterized by typical
      morphology and biallelic inactivation of the SMARCB1 (INI1/hSNF5/BAF47) gene on
      chromosome 22q.2 which encodes a subunit of the SWI/SNF ATP-dependent chromatin
      remodeling complex. Congenital infantile disseminated MRT represents a unique
      clinicopathologic presentation of this tumor. We report a case occurring in a
      female neonate who presented at birth a voluminous left thigh mass. Surgical
      biopsy performed at day 9 showed morphology and immunoprofile of MRT. Staging
      evaluation identified hypercalcemia and distant nodules. The mass showed rapid
      growth. Despite chemotherapy, the tumor progressed with exteriorization through
      the biopsy scar. Chemotherapy was discontinued and treatment limited to
      palliative care and the child died on day 51. The tumor was homozygous for the
      SMARCB1 deletion with apparent de novo heterozygous germ line deletion in the
      infant, not identified in the parents. 

PMID- 25751459
TI  - Applying the Ockham's razor... or the Hickam's dictum?

PMID- 25751460
TI  - The cover page.

PMID- 25751461
TI  - The noble art of healing.

PMID- 25751462
TI  - Treatment of odontoid fractures.

PMID- 25751463
TI  - Deep brain stimulation: current status.
AB  - In the last two decades, applications of deep brain stimulation (DBS) have
      expanded rapidly in the field of neurosciences. The most common indications for
      DBS are Parkinson's disease, medically refractory seizures, essential tremors,
      and primary dystonia. This device has also been used as an investigational tool
      in patients having Tourette's syndrome, tardive dyskinesia, and refractory
      seizures. In the field of psychiatry, DBS has been used for the treatment of
      refractory obsessive compulsive disorder and depression. The complications are
      mainly related to surgery, the device, and its stimulation. This article provides
      an overview of the current status and recent advances in the field of DBS. 

PMID- 25751464
TI  - Elucidating the role of incidental use of beta-blockers in patients with
      metastatic brain tumors in controlling tumor progression and survivability.
AB  - BACKGROUND: Beta-adrenergic antagonists have demonstrated beneficial effects in
      tumor progression and survivability in patients with various cancers by
      inhibiting norepinephrine-induced tumor cell migration. However, little is known
      about their effects on the outcomes of metastatic brain tumors (MBTs). This study
      was undertaken to evaluate the effects of beta-blockers, if any, on the outcome
      of MBTs, and their possible role in controlling tumor progression and
      survivability. MATERIALS AND METHODS: A retrospective cohort analysis of 225
      patients identified as having MBTs presenting to our institution from 2001
      through 2013 was conducted by reviewing electronic patient records. Patients were
      categorized into three groups: Group A comprised hypertensives on beta-blockers
      only (40, 18%), Group B comprised hypertensive patients on antihypertensive
      medications other than beta-agonists (65, 29%), and Group C comprised
      normotensives (120, 53%). All outcomes were compared using the data on pre - and
      post-gamma knife radiosurgery (GKRS) for these groups. One-way analysis of
      variance (ANOVA) was used to compare the radiological and clinical outcomes in
      the patient population following beta-blockers usage in Group A versus groups B
      and C. Cox regression model was used to demonstrate prognostic factors for the
      outcome in patients having different primaries. Overall survival period was
      plotted on Kaplan-Meier curves. The log-rank (Mantel-Cox) test was used to
      analyze the survival difference in the cases. P < 0.05 was considered
      significant. RESULTS: The mean age of patients was 57.34 +/- 10.98 years (range:
      30-87 years) and 44% were males. More than half (130/225, 58%) of patients with
      MBT had their primary tumor source in the lung, 16% in the breast, and 7% each in
      the kidneys and the rectum. Frontal lobe was the most commonly affected (80,
      35.5%). Statistically significant control of tumor growth (P = 0.001), tumor
      progression (P = 0.0001), and higher survival outcomes (P = 0.015) were observed
      in Group A as compared to other groups. In comparing the different groups, breast
      primaries showed the strongest correlation to survival benefit (P = 0.049) from
      beta-blocker usage as a primary antihypertensive medication. CONCLUSION:
      Concomitant use of beta-blockers with conventional therapy may offer potential
      benefit to hypertensive patients developing MBTs by ameliorating tumor
      progression and conferring a survival advantage. This effect was most notable in
      patients with primary tumors originating in the breast. Prospective studies,
      molecular research, and randomized controlled trials are warranted to further
      explore this promising effect.

PMID- 25751465
TI  - Modification of Nurick scale and Japanese Orthopedic Association score for Indian
      population with cervical spondylotic myelopathy.
AB  - AIMS: Existing scales for functional grading of patients with cervical
      spondylotic myelopathy (CSM), such as the Nurick scale and modified Japanese
      Orthopedic Association (mJOA) scale, do not address certain culture-specific
      activities of the Indian population while grading patients with CSM. MATERIALS
      AND METHODS: We modified the Nurick scale and mJOA scale to develop the Indian
      modifications of Nurick (imNurick) and mJOA scales (imJOA and imJOA scales),
      respectively, and then evaluated these modified scales in 93 patients with CSM to
      determine whether these modifications had a meaningful impact on the functional
      scores of these patients. RESULTS: There was good interobserver agreement in the
      assessments documented in all the four scales (Nurick grade, imNurick grade, mJOA
      scale, and imJOA scale) (kappa = 1). Both Nurick grading (z = 4.4, P = 0.00) and
      imNurick grading (z = 5.5, P = 0.00) had a valid construct when tested against
      lower limb mJOA (llmJOA) score. The Indian modified upper limb JOA (imulmJOA)
      score too had a good construct with modified upper limb JOA (ulmJOA) score (z =
      2.5, P = 0.01). There was substantial agreement between Nurick grade and imNurick
      grade (weighted kappa of 0.75) when taken as a whole group and between ulmJOA
      score and imulmJOA scores (weighted kappa of 0.75). However, there was
      significant disagreement between the Nurick grade and imNurick grade scales in
      patients who were Nurick grade 2 and 3 (kappa = 0.07). CONCLUSIONS: The proposed
      Indian modifications of Nurick grade and mJOA scale that incorporate the ethnic
      practices of the Indian population and some Asian population are better
      discriminators of different levels of functional ability among patients with CSM
      in this population, as compared to the existing Nurick grading and mJOA scale.

PMID- 25751466
TI  - Series of paraneoplastic vasculitic neuropathy: a rare, potentially treatable
      neuropathy.
AB  - BACKGROUND: Paraneoplastic vasculitic neuropathy (PVN) is a rare paraneoplastic
      syndrome. It is characterized by non-systemic subacute vasculitic neuropathy. It
      is most commonly associated with small cell lung cancers (SCLC) and lymphomas.
      PVN presents as a painful symmetrical or asymmetrical sensorimotor axonal
      neuropathy. The neurological symptoms may predate the tumor and may be the
      initial manifestations, or they may develop after a tumor is diagnosed.
      Recognition of this entity is important because of its potential treatability.
      AIM: To study the clinical features of PVN and briefly review the literature.
      MATERIALS AND METHODS: The data was collected retrospectively from the medical
      records of our hospital. RESULTS: Of the 14 cases of paraneoplastic neuropathies,
      4 had a PVN. The age of onset was more than 50 years and there was no sex
      preponderance. Pain was seen in three patients. Two patients were previously
      treated for a thymoma. Two patients, following their presentation with PVN, were
      diagnosed with a colonic carcinoma and lung carcinoma, respectively. CONCLUSIONS:
      The recognition of PVN is important as this syndrome may respond to
      immunosuppression and tumor removal.

PMID- 25751467
TI  - Prevalence of UGT1A6 polymorphisms in children with epilepsy on valproate
      monotherapy.
AB  - BACKGROUND: Valproate is a commonly used anticonvulsant drug. Uridine 5?
      diphospho (UDP)-glucuronosyltransferase (UGT) contributes to around 50% of
      valproate metabolism and its polymorphisms may be important for explaining the
      considerable variation in valproate levels in patients with epilepsy. AIM: This
      study was aimed to analyze the genetic polymorphisms of UGT1A6 in Indian children
      with epilepsy and their potential influence on the pharmacokinetics of valproate.
      SETTING AND DESIGN: This cross-sectional study was carried out in the Department
      of Pediatrics, All India Institutes of Medical Sciences (AIIMS), New Delhi,
      between March 2011 and July 2012. MATERIALS AND METHODS: Children aged 3-12 years
      diagnosed with epilepsy on valproate monotherapy for at least 1 month were
      enrolled. They underwent a detailed clinical examination. The UGT1A6
      polymorphisms were detected by polymerase chain reaction-restriction fragment
      length polymorphism (PCR-RFLP). Random samples were checked by genetic
      sequencing. The steady-state plasma concentrations of valproate were measured by
      High Performance Liquid Chromatography (HPLC) and associated with UGT1A6
      polymorphisms. RESULTS: A total of 80 children were studied. The prevalence of
      UGT1A6 T19G was as follows: TT (45%), TG (38.8%), and GG (16.3%); that of UGT1A6
      A541G was: AA (48.8%), AG (38.8%), and GG (12.5%); and that of UGT1A6 A552C was:
      AA (43.8%), AC (40%), and CC (16.3%). The association between valproate doses or
      standardized serum valproate concentration and the various UGT1A6 genotypes could
      not be studied reliably in this small study population. CONCLUSIONS: The
      frequencies of UGT1A6 geneotypes and alleles were reported in the study
      population.

PMID- 25751468
TI  - Surgical management of odontoid fractures at level one trauma center: a single
      center series of 142 cases.
AB  - INTRODUCTION: Odontoid fractures constitute 9-20% of all adult cervical spine
      fractures. The present study was carried out to focus on the nuances involved in
      the surgical management of odontoid fractures. MATERIALS AND METHODS: Patients
      with an odontoid fracture, admitted for surgical stabilization, between January
      2008 and March 2014, were included in the study. RESULTS: Among 142 patients [127
      male and 15 female patients; median age: 28 years range 4-75 years], type II
      odontoid fractures were present in 111, type IIA fractures in 8, and type III
      fractures in 23 patients. 58.5% patients had been involved in a motor vehicular
      accident while 38.7% had sustained a fall. Eighty-five patients (59.9%) with a
      well-reduced fracture and an intact transverse ligament underwent anterior
      odontoid screw (OS) placement; the other 57 patients (40.1%) underwent posterior
      fixation (PF). The mean follow-up duration was 22 months (range: 6 months-5.4
      years). OS placement was successful in 82 patients (96.5%) with a fusion rate of
      95% (95.8% in type II, 100% in type III, and 75% in type IIA odontoid fractures).
      The procedure-related morbidity was 11.7%. One patient died of sub-arachnoid
      hemorrhage (SAH) that occurred during OS placement. The PF procedures had a
      better fusion rate (96.5%). The latter patients, however, had significant
      restriction of their neck movements and an overall morbidity of 8.7%. The
      revision surgery rates after OS placement and PF fixation were 7% and 3.5%,
      respectively. CONCLUSIONS: Anterior OS fixation shows excellent fusion rates and
      should be the first-line management in reduced/non-displaced acute type II
      (including type IIA) and high type III odontoid fractures as it preserves
      cervical motion. PF, that has also been associated with an excellent fusion rate,
      should be reserved for patients where OS fixation has either failed or has not
      been feasible.

PMID- 25751469
TI  - Analyzing functional, structural, and anatomical correlation of hemispheric
      language lateralization in healthy subjects using functional MRI, diffusion
      tensor imaging, and voxel-based morphometry.
AB  - CONTEXT: To evaluate the efficacy of diffusion fiber tractography (DFT) and voxel
      based morphometry (VBM) for lateralizing language in comparison with functional
      magnetic resonance imaging (fMRI) to noninvasively assess hemispheric language
      lateralization in normal healthy volunteers. AIMS: The aim of the present study
      is to evaluate the concordance of language lateralization obtained by diffusion
      tensor imaging (DTI) and VBM to fMRI, and thus to see whether there exists an
      anatomical correlate for language lateralization result obtained using fMRI.
      SETTINGS AND DESIGN: This is an advanced neuroimaging study conducted in normal
      healthy volunteers. SUBJECTS AND METHODS: Fifty-seven normal healthy subjects (39
      males and 18 females; age range: 15-40 years) underwent language fMRI and 30
      underwent direction DTI. fMRI language laterality index (LI), fiber tract
      asymmetry index (AI), and tract-based statistics of dorsal and ventral language
      pathways were calculated. The combined results were correlated with VBM-based
      volumetry of Heschl's gyrus (HG), planum temporale (PT), and insula for
      lateralization of language function. STATISTICAL ANALYSIS USED: A linear
      regression analysis was done to study the correlation between fMRI, DTI, and VBM
      measurements. RESULTS: A good agreement was found between language fMRI LI and
      fiber tract AI, more specifically for arcuate fasciculus (ArcF) and inferior
      longitudinal fasciculus (ILF). The study demonstrated significant correlations (P
      < 0.05) between blood-oxygen-level dependent (BOLD) fMRI activations, tract-based
      statistics, and PT and HG volumetry for determining language lateralization.
      CONCLUSIONS: A strong one-to-one correlation between fMRI, laterality index, DTI
      tractography measures, and VBM-based volumetry measures for determining language
      lateralization exists.

PMID- 25751470
TI  - A comparative study of mPCR, MLPA, and muscle biopsy results in a cohort of
      children with Duchenne muscular dystrophy: a first study.
AB  - BACKGROUND: Multiplex ligation-dependant probe amplification (MLPA) is a highly
      sensitive and rapid alternative to multiplex polymerase chain reaction (PCR).
      Muscle biopsy should be reserved for mutation-negative cases. MATERIALS AND
      METHODS: An attempt was made to compare the sensitivity and pattern of mutations
      by mPCR and MLPA testing in a cohort with suspected Duchenne muscular dystrophy
      (DMD). Eighty-three children with DMD were enrolled for mPCR and MLPA testing.
      MLPA-negative cases underwent muscle immunohistochemistry (IHC) for dystrophin.
      RESULTS: Mean age of onset was 45.3 +/- 25.2 months; and mean duration of illness
      was - 53.3 +/- 30.8 months. About 11.9% patients had delayed mental milestones.
      Mean creatine kinase (CK) value was 12136.1 +/- 8591.1 LU/L. mPCR detected
      deletions in 60/83 (72.3%). Proximal deletions were found in 8 (8.6%), distal
      deletions in 51 (54.8%), and, both proximal and distal deletions were found in 1.
      Majority of the deletions were <5 exons [34(36.6%)]; two showed large deletions
      of >10 exons (2.2%). Deletions in hot spot region occurred in 83.3%. MLPA in the
      same 83 samples detected deletions in an additional six cases and duplications in
      6 (6.5%). Combined detection rate of deletion was 79.5%. Duplications were found
      in 7.2% of the whole sample. MLPA showed 14 (15.1%) proximal and 57 (61.3%)
      distal deletions, and proximal and distal deletion in 1. Large deletions (>10
      exons) were seen in 6.5%, and single deletions were observed in 24 (36.4%). Most
      common multiple exon deletion was seen at 45-52 region in 7 samples (10.6%).
      Longest duplication extended from exon 60 to 66. In the 11 MLPA-negative cases,
      IHC confirmed dystrophinopathy in 36.36%, sarcoglycanopathy in 36.36%, and no
      deficiency in 27.27%. CONCLUSIONS: This is the first study from India and
      possibly in English literature, comparing the sensitivity and pattern of
      mutations by both mPCR and MLPA in the same cohort of DMD. It further validates
      that 36.4% of MLPA-negative cases were confirmed to have DMD by IHC. The clinical
      accuracy has been very high in our cohort. MLPA-negative samples should be
      subjected for next-generation sequencing before contemplating a biopsy.

PMID- 25751471
TI  - Validity of Montreal Cognitive Assessment in non-english speaking patients with
      Parkinson's disease.
AB  - BACKGROUND: The Montreal Cognitive Assessment is a brief and easy screening tool
      for accurately testing cognitive dysfunction in Parkinson's disease. We tested
      its validity for use in non-English (Malayalam) speaking patients with
      Parkinson's disease. MATERIALS AND METHODS: We developed a Malayalam (a south
      Indian language) version of Montreal Cognitive Assessment and applied to 70
      patients with Parkinson's disease and 60 age- and education-matched healthy
      controls. Metric properties were assessed, and the scores were compared with the
      performance in validated Malayalam versions of Mini Mental Status Examination and
      Addenbrooke's Cognitive Examination. RESULTS: The Montreal Cognitive Assessment
      Malayalam showed good internal consistency and test-retest reliability and its
      scores correlated with Mini Mental Status Examination (patients: R = 0.70; P <
      0.001; healthy controls: R = 0.26; P = 0.04) and Addenbrooke's Cognitive
      Examination (patients: R = 0.8; P < 0.001; healthy controls: R = 0.52; P < 0.001)
      scores. CONCLUSION: This study establishes the reliability of cross-cultural
      adaptation of Montreal Cognitive Assessment for assessing cognition in Malayalam
      speaking Parkinson's disease patients for early screening and potential future
      interventions for cognitive dysfunction.

PMID- 25751472
TI  - Cavernoma of the septum pellucidum in the region of foramen of Monro.
AB  - A rare case of cavernoma in the region of the septum pellucidum is reported. A 35
      year-old female patient presented with chronic headaches. Her neurological exam
      was normal. Her magnetic resonance (MR) imaging showed a lesion within the
      inferior aspect of the septum pellucidum extending into the anterior third
      ventricular region, blocking the foramen of Monro, resulting in moderate
      supratentorial asymmetrical hydrocephalus. A central neurocytoma or subependymoma
      was suspected on imaging. Complete excision of the septum pellucidum cavernoma
      was performed using microneurosurgical techniques through an interhemispheric
      transcallosal route. The patient had an excellent outcome and is cured. Although
      rare, septum pellucidum cavernomas should be considered in the differential
      diagnosis of anterior third ventricular lesions in the region of foramen of
      Monro. The unusual location, atypical radiological features, differential
      diagnosis as well as surgical nuances in the management of a cavernoma in the
      septum pellucidum and anterior third ventricular region are discussed in the
      light of current literature. 

PMID- 25751473
TI  - An unusual case of inflammatory necrotizing myopathy and neuropathy with pipestem
      capillaries.
AB  - Necrotizing myopathy with pipestem capillaries is a form of chronic inflammatory
      myopathy, with histopathology showing necrotizing myopathy, minimal cellular
      infiltration, and microangiopathy. A 30-year-old female presented with
      progressive limb weakness of 6 months, with skin pigmentation and Raynaud's
      phenomenon. Serum creatine phosphokinase was 3990 u/L. Muscle biopsy showed
      necrotic fibers, focal sparse perivascular inflammation/perifascicular atrophy,
      endomysial/epimysial vessel wall thickening with luminal narrowing. The features
      were of inflammatory necrotizing myopathy and neuropathy with pipestem
      capillaries/microangiopathy. She was pulsed with intravenous immunoglobulin,
      methylprednisolone, and cyclophosphamide and showed a good improvement. In the
      absence of widespread inflammatory response and classical histopathology
      findings, it is important to diagnose this condition as it shows a good response
      to aggressive and prolonged immunotherapy. 

PMID- 25751474
TI  - Clinicopathological correlates of primary central nervous system lymphoma:
      experience from a tertiary care center in South India.
AB  - BACKGROUND: Primary central nervous system lymphomas (PCNSL) constitute a rare
      group of extranodal non-Hodgkin's lymphomas (NHLs). AIM: To study the clinical
      and immunophenotypic profile of patients with a PCNSL who presented between the
      years 2000 and 2013 in a tertiary care center in South India. MATERIALS AND
      METHODS: This was a retrospective study. Demographic and clinical data were
      obtained from the clinical case records. INCLUSION CRITERIA: Cases of PCNSL
      involving brain. EXCLUSION CRITERIA: Cases of PCNSL involving the spinal cord,
      meninges and orbit as well as intravascular large B-cell lymphoma, lymphomas with
      evidence of systemic disease or secondary lymphomas. Archived slides and tissue
      blocks were retrieved. All cases had hematoxylin and eosin stained sections and
      immunohistochemistry for CD20, CD3, and MIB-1. Additional immunohistochemistry
      was performed for CD10, BCL6, and MUM1 on paraffin blocks with sufficient tissue.
      RESULTS: There were a total of 73 cases with the mean age of presentation being
      45.9 years (range 8-71 years) and with a male predominance (male: female (M:F) =
      2.3:1). Headache was the commonest presenting complaint. The mean duration of
      symptoms was 10.6 weeks. All patients were immunocompetent. Most tumors were
      supratentorial in location. Out of 73 cases, 70 presented with a diffuse large B
      cell lymphoma (DLBCL), two with a Burkitt's lymphoma, and one with a lymphomatoid
      granulomatosis. Only 51 of the DLBCL cases had sufficient tissue for additional
      studies. Non-germinal center was the most common phenotype seen in 65.7% (33/51)
      of cases. Germinal center B-cell (GCB) phenotype was seen in 18/51 cases (34.3%).
      CONCLUSION: DLBCL constituted the majority of PCNSLs and although non-germinal
      center was the predominant phenotype, more than a third of the cases were of the
      GCB phenotype. As the germinal center phenotype is known to have a better
      prognosis, further studies to explore its relevance in the Asian population are
      indicated.

PMID- 25751475
TI  - Current perspectives in the management of glomus jugulare tumors.
AB  - Glomus jugulare tumors are benign but locally aggressive tumors. Their location,
      spread to adjacent areas and biological behavior have been extensively studied
      and reported. However, controversy exists regarding the role of surgery and
      stereotactic radiosurgery. The optimal plan of management of the tumor in close
      proximity to the facial and lower cranial nerves, the internal carotid and
      vertebral arteries, the venous sinuses, and the neuraxis is still nebulous. This
      review will discuss the differing viewpoints and attempts to propose a rational
      strategy in dealing with these tumors. 

PMID- 25751476
TI  - History of Neurosurgery at National Institute of Mental Health and Neurosciences:
      an epitome of steady growth.

PMID- 25751477
TI  - Aneurysm clips: what every resident should know.

PMID- 25751478
TI  - A summary of some of the recently-published, seminal papers in neuroscience.

PMID- 25751479
TI  - A case of vertebral artery dissection associated with ipsilateral posterior
      inferior cerebellar artery dissection.

PMID- 25751480
TI  - An unusual cause for a rare neuropathy: pudendal nerve entrapment syndrome
      secondary to obturator internus muscle edema.

PMID- 25751481
TI  - Complete intracranial migration of a ventriculoperitoneal shunt: rare
      complication of a common procedure.

PMID- 25751482
TI  - Intractable yawning caused by foramen magnum meningioma in a patient with
      neurofibromatosis type 2.

PMID- 25751483
TI  - Subacute sclerosing panencephalitis masquerading as rapid-onset dystonia
      Parkinsonism in a child.

PMID- 25751484
TI  - Cervical burst fracture caused by brown tumor.

PMID- 25751485
TI  - Delayed appearance and rupture of a post-traumatic supraclinoid aneurysm in a 2
      year-old child.

PMID- 25751486
TI  - Primary spinal extraosseous cervical chondroma in an adult.

PMID- 25751487
TI  - Central retinal artery occlusion with ophthalmoparesis in spontaneous carotid
      artery dissection.

PMID- 25751488
TI  - Isolated conus-epiconus neurocysticercosis.

PMID- 25751489
TI  - Reversible onychomadesis following exposure to carbamazepine.

PMID- 25751490
TI  - Spinal lipoma with tibial hemimelia-incidental or causative? Revisiting the
      McCredie-McBride hypothesis.

PMID- 25751491
TI  - Giant eccentric target sign.

PMID- 25751492
TI  - Correction to "Dynamic kinetic resolution of alpha-keto esters via asymmetric
      transfer hydrogenation".

PMID- 25751493
TI  - Racial differences in depressive symptoms and self-rated health among breast
      cancer survivors on aromatase inhibitor therapy.
AB  - The goal of this survey-based study was to examine whether aromatase inhibitor
      (AI) therapy was associated with depressive symptoms and self-rated health among
      Black and White breast cancer survivors (N = 761). Results showed that among
      Black, but not White, breast cancer survivors current AI therapy was associated
      with a significant increase in the odds of both depressive symptoms (OR 3.59; 95%
      CI 1.01, 13.00) and poorer self-rated health (OR 3.16; 95% CI 1.06, 9.46).
      Presence of pain was significantly associated with increased odds of both
      outcomes among both groups. The findings underscore the importance of addressing
      not only physical but mental health among breast cancer survivors on AIs,
      especially those of Black race. 

PMID- 25751494
TI  - Efficient and selective Cu/nitroxyl-catalyzed methods for aerobic oxidative
      lactonization of diols.
AB  - Cu/nitroxyl catalysts have been identified that promote highly efficient and
      selective aerobic oxidative lactonization of diols under mild reaction conditions
      using ambient air as the oxidant. The chemo- and regioselectivity of the reaction
      may be tuned by changing the identity of the nitroxyl cocatalyst. A Cu/ABNO
      catalyst system (ABNO = 9-azabicyclo[3.3.1]nonan-N-oxyl) shows excellent
      reactivity with symmetrical diols and hindered unsymmetrical diols, whereas a
      Cu/TEMPO catalyst system (TEMPO = 2,2,6,6-tetramethyl-1-piperidinyl-N-oxyl)
      displays excellent chemo- and regioselectivity for the oxidation of less hindered
      unsymmetrical diols. These catalyst systems are compatible with all classes of
      alcohols (benzylic, allylic, aliphatic), mediate efficient lactonization of 1,4-,
      1,5-, and some 1,6-diols, and tolerate diverse functional groups, including
      alkenes, heterocycles, and other heteroatom-containing groups. 

PMID- 25751495
TI  - XPS investigation of surface reactivity of electrode materials: effect of the
      transition metal.
AB  - The role of the transition metal nature and Al2O3 coating on the surface
      reactivity of LiCoO2 and LiNi(1/3)Mn(1/3)Co(1/3)O2 (NMC) materials were studied
      by coupling chemisorption of gaseous probes molecules and X-ray photoelectron
      (XPS) spectroscopy. The XPS analyses have put in evidence the low reactivity of
      the LiMO2 materials toward basic gaseous probe (NH3). The reactivity toward SO2
      gaseous probe is much larger (roughly more than 10 times) and strongly influenced
      by the nature of metal. Only one adsorption mode (redox process producing
      adsorbed sulfate species) was observed at the LiCoO2 surface, while NMC materials
      exhibit sulfate and sulfite species at the surface. On the basis of XPS analysis
      of bare materials and previous theoretical work, we propose that the acid-base
      adsorption mode involving the Ni(2+) cation is responsible for the sulfite
      species on the NMC surface. After Al2O3 coating, the surface reactivity was
      clearly decreasing for both LiCoO2 and NMC materials. In addition, for LiCoO2,
      the coating modifies the surface reactivity with the identification of both
      sulfate and sulfite species. This result is in line with a change in the
      adsorption mode from redox toward acid-base after Al/Co substitution. In the case
      of NMC materials, the coating induced a decrease of the sulfite species content
      at the surface. This phenomenon can be related to the cation mixing effect in the
      NMC.

PMID- 25751496
TI  - Cleaning Efficiencies of Three Cleaning Agents on Four Different Surfaces after
      Contamination by Gemcitabine and 5-fluorouracile.
AB  - Occupational exposure to antineoplastic drugs has been documented for decades
      showing widespread contamination in preparation and administration areas. Apart
      from preventive measures, efficient cleaning of surfaces is indispensable to
      minimize the exposure risk. The aim of this study was to evaluate the efficiency
      of three cleaning agents after intentional contamination by gemcitabine (GEM) and
      5-fluorouracile (5-FU) on four different surface types usually installed in
      healthcare settings. Glass, stainless steel, polyvinylchloride (PVC), and
      laminated wood plates were contaminated with 20 ng/MUl GEM and 2 ng/MUl 5-FU
      solutions. Wipe samples were analyzed for drug residues after cleaning with a)
      distilled water, b) aqueous solution containing sodium dodecyl sulfate (10 mM)
      and 2-propanol (SDS-2P), and c) Incides N (pre-soaked) alcoholic wipes.
      Quantification was performed by high-performance liquid chromatography (HPLC) for
      GEM and gas chromato-graphy-tandem mass spectrometry (GCMS/MS) for 5-FU. Recovery
      was determined and cleaning efficiency was calculated for each scenario. Mean
      recoveries were 77-89% for GEM and 24-77% for 5-FU and calculated cleaning
      efficiencies ranged between 95 and 100% and 89 and 100%, respectively. Residual
      drug amounts were detected in the range nd (not detected) - 84 ng GEM/sample and
      nd - 6.6 ng 5-FU/sample depending on surface type and cleaning agent. Distilled
      water and SDS-2P had better decontamination outcomes than Incides N wipes on
      nearly all surface types, especially for GEM. Regarding 5-FU, the overall
      cleaning efficiency was lower with highest residues on laminated wood surfaces.
      The tested cleaning procedures are shown to clean glass, stainless steel, PVC,
      and laminated wood with an efficiency of 89-100% after contamination with GEM and
      5-FU. Nevertheless, drug residues could be verified by wipe samples. Pure
      distilled water and SDS in an alcoholic-aqueous solution expressed an efficient
      cleaning performance, especially with respect to GEM. The study results
      demonstrate the need to adapt cleaning procedures to the variety of drugs and
      surface types to develop effective decontamination strategies.

PMID- 25751497
TI  - Using latent class analysis to identify academic and behavioral risk status in
      elementary students.
AB  - Identifying classes of children on the basis of academic and behavior risk may
      have important implications for the allocation of intervention resources within
      Response to Intervention (RTI) and Multi-Tiered System of Support (MTSS) models.
      Latent class analysis (LCA) was conducted with a sample of 517 third grade
      students. Fall screening scores in the areas of reading, mathematics, and
      behavior were used as indicators of success on an end of year statewide
      achievement test. Results identified 3 subclasses of children, including a class
      with minimal academic and behavioral concerns (Tier 1; 32% of the sample), a
      class at-risk for academic problems and somewhat at-risk for behavior problems
      (Tier 2; 37% of the sample), and a class with significant academic and behavior
      problems (Tier 3; 31%). Each class was predictive of end of year performance on
      the statewide achievement test, with the Tier 1 class performing significantly
      higher on the test than the Tier 2 class, which in turn scored significantly
      higher than the Tier 3 class. The results of this study indicated that distinct
      classes of children can be determined through brief screening measures and are
      predictive of later academic success. Further implications are discussed for
      prevention and intervention for students at risk for academic failure and
      behavior problems. (PsycINFO Database Record 

PMID- 25751498
TI  - Invigorating science, practice, and policy relevant to school psychology
      throughout the world.

PMID- 25751499
TI  - Enhanced T-cell immunity to osteosarcoma through antibody blockade of PD-1/PD-L1
      interactions.
AB  - Osteosarcoma is the most common bone cancer in children and adolescents. Although
      70% of patients with localized disease are cured with chemotherapy and surgical
      resection, patients with metastatic osteosarcoma are typically refractory to
      treatment. Numerous lines of evidence suggest that cytotoxic T lymphocytes (CTLs)
      limit the development of metastatic osteosarcoma. We have investigated the role
      of PD-1, an inhibitory TNFR family protein expressed on CTLs, in limiting the
      efficacy of immune-mediated control of metastatic osteosarcoma. We show that
      human metastatic, but not primary, osteosarcoma tumors express a ligand for PD-1
      (PD-L1) and that tumor-infiltrating CTLs express PD-1, suggesting this pathway
      may limit CTLs control of metastatic osteosarcoma in patients. PD-L1 is also
      expressed on the K7M2 osteosarcoma tumor cell line that establishes metastases in
      mice, and PD-1 is expressed on tumor-infiltrating CTLs during disease
      progression. Blockade of PD-1/PD-L1 interactions dramatically improves the
      function of osteosarcoma-reactive CTLs in vitro and in vivo, and results in
      decreased tumor burden and increased survival in the K7M2 mouse model of
      metastatic osteosarcoma. Our results suggest that blockade of PD-1/PD-L1
      interactions in patients with metastatic osteosarcoma should be pursued as a
      therapeutic strategy. 

PMID- 25751500
TI  - Enhanced dendritic cell-based immunotherapy using low-dose cyclophosphamide and
      CD25-targeted antibody for transplanted Lewis lung carcinoma cells.
AB  - Regulatory T cells (Tregs) is one of the main obstacles to the success of cancer
      immunotherapy. The effect of dendritic cell (DC)-based immunotherapy can be
      attenuated by immune suppressive functions of Tregs. We used a CD25-targeted
      antibody and low-dose cyclophosphamide (CTX) as immunomodulators to increase the
      antitumor effect of intratumoral injection of immature DCs into the irradiated
      tumor cells (IR/iDC). CTX or CD25-targeted antibody alone showed a significant
      reduction in the number of Tregs within the tumor microenvironment. When they are
      combined with IR/iDC, the number of Tregs was further reduced. Although IR/IDC
      showed strong antitumor effects such as reduction in tumor growth, increase in
      Th1 immune response, and improvement of survival, the therapeutic effect was
      further improved by combining treatments with immunomodulators. CTX and CD25
      targeted antibody showed no significant difference in tumor growth when combined
      with IR/iDC, but CTX further increased the number of interferon (IFN)-gamma
      secreting T cells, cytotoxicity, and survival rate. Although irradiation induced
      depletion of T lymphocytes, administration of DCs recovered this depletion.
      Particularly, the lymphocytes were more significantly increased when CTX and
      IR/iDC were combined. Low-dose CTX has already been used as an immunomodulator in
      clinical trials, and it offers several advantages, including convenience, low
      cost, and familiarity to clinicians. However, CD25-targeted antibody cannot only
      deplete Tregs, but also may affect IL-2-dependent effector T lymphocytes.
      Therefore, CTX is an effective means to inhibit Tregs, and an effective
      immunomodulatory agent for multimodality therapy such as combination treatment of
      conventional cancer therapy and immunotherapy. 

PMID- 25751501
TI  - Proapoptotic and antiapoptotic proteins of the Bcl-2 family regulate sensitivity
      of pancreatic cancer cells toward gemcitabine and T-cell-mediated cytotoxicity.
AB  - Sensitivity of carcinoma cells towards gemcitabine (Gem) has been linked to
      mitochondrial apoptotic proteins. Recently, we described synergistic efficacy of
      Gem-based chemoimmunotherapy and a dendritic cell (DC) tumor vaccine in a murine
      pancreatic carcinoma model. Here, we investigated the role of the mitochondrial
      proteins Bcl-2, Bcl-xL, and Bax for sensitization of pancreatic carcinoma cells
      toward T-cell-mediated cytotoxicity alone and in combination with Gem. Bcl-2
      expression was silenced by siRNA in Panc02 pancreatic cancer cells expressing the
      model antigen ovalbumin (PancOVA). Tumor cells were treated with Gem and/or
      siRNA, and cytotoxicity induced by OVA-specific cytotoxic T lymphocytes (CTL)
      from OT-1 mice was assessed. Gem-induced and T-cell-induced cytotoxicity was also
      studied in human Colo357 pancreatic cancer cell lines overexpressing Bax or Bcl
      xL. Apoptosis induction by Fas-activating antibody was measured by Annexin V
      staining. The in vivo capacity of Bcl-2 siRNA to augment CTL efficacy induced by
      DC vaccinations was assessed in C57BL/6 mice bearing PancOVA tumors. PancOVA
      cells treated with Bcl-2 siRNA were sensitized towards both Gem and T-cell
      mediated killing; combination therapy exhibited an additive effect. Bax
      overexpression sensitized Colo357 cells to both Gem-mediated and T-cell-mediated
      cytotoxicity, whereas Bcl-xL overexpression was inhibitory. Combining Bcl-2
      silencing with DC therapy improved tumor control in the PancOVA model in vivo
      without affecting the number of tumor-reactive CTL. In conclusion, expression of
      Bcl-2, Bcl-xL, and Bax in pancreatic tumor cells determines sensitivity towards
      both Gem-mediated and CTL-mediated toxicity. Bcl-2 silencing could be exploited
      therapeutically in tumor vaccine approaches. 

PMID- 25751503
TI  - Attitudes toward Assisted Suicide: Does Family Context Matter?
AB  - Little is known about how family-related contextual variables impact attitudes
      toward assisted suicide. A probability sample (N = 272) responded to a multiple
      segment factorial vignette designed to examine the effects of 6 variables-patient
      sex, age, type of illness, relationship status, parenthood status, and family
      support-on attitudes toward physician- and family-assisted suicide. Respondents
      were more likely to support physician-assisted suicide if they heard about an
      older patient or a patient experiencing physical pain than a younger patient or
      one suffering from depression, respectively. For family-assisted suicide,
      respondent support was higher when the patient had physical pain than depression,
      and when the patient's spouse or friend was supportive of the wish to die than
      unsupportive. Attitudes about physician and family obligation to inform others
      were affected by type of illness, relationship status, family support, and
      respondent education and religiosity. The experience of pain, motivations for
      family involvement, confidentiality issues, and physicians' biases concerning
      assisted suicide are discussed. 

PMID- 25751502
TI  - Large-scale clinical-grade retroviral vector production in a fixed-bed
      bioreactor.
AB  - The successful genetic engineering of patient T cells with gamma-retroviral
      vectors expressing chimeric antigen receptors or T-cell receptors for phase II
      clinical trials and beyond requires the large-scale manufacture of high-titer
      vector stocks. The production of retroviral vectors from stable packaging cell
      lines using roller bottles or 10- to 40-layer cell factories is limited by a
      narrow harvest window, labor intensity, open-system operations, and the
      requirement for significant incubator space. To circumvent these shortcomings, we
      optimized the production of vector stocks in a disposable fixed-bed bioreactor
      using good manufacturing practice-grade packaging cell lines. High-titer vector
      stocks were harvested over 10 days, representing a much broader harvest window
      than the 3-day harvest afforded by cell factories. For PG13 and 293Vec packaging
      cells, the average vector titer and the vector stocks' yield in the bioreactor
      were higher by 3.2- to 7.3-fold, and 5.6- to 13.1-fold, respectively, than those
      obtained in cell factories. The vector production was 10.4 and 18.6 times more
      efficient than in cell factories for PG13 and 293Vec cells, respectively.
      Furthermore, the vectors produced from the fixed-bed bioreactors passed the
      release test assays for clinical applications. Therefore, a single vector lot
      derived from 293Vec is suitable to transduce up to 500 patients cell doses in the
      context of large clinical trials using chimeric antigen receptors or T-cell
      receptors. These findings demonstrate for the first time that a robust fixed-bed
      bioreactor process can be used to produce gamma-retroviral vector stocks scalable
      up to the commercialization phase. 

PMID- 25751504
TI  - The real-time in vivo electrochemical measurement of nitric oxide and carbon
      monoxide release upon direct epidural electrical stimulation of the rat
      neocortex.
AB  - This study reports real-time, in vivo functional measurement of nitric oxide (NO)
      and carbon monoxide (CO), two gaseous mediators in controlling cerebral blood
      flow. A dual electrochemical NO/CO microsensor enables us to probe the complex
      relationship between NO and CO in regulating cerebrovascular tone. Utilizing this
      dual sensor, we monitor in vivo change of NO and CO simultaneously during direct
      epidural electrical stimulation of a living rat brain cortex. Both NO and CO
      respond quickly to meet physiological needs. The neural system instantaneously
      increases the released amounts of NO and CO to compensate the abrupt, yet
      transient hypoxia that results from epidural electrical stimulation. Intrinsic
      signal optical imaging confirms that direct electrical stimulation elicits
      robust, dynamic changes in cerebral blood flow, which must accompany NO and CO
      signaling. The addition of l-arginine (a substrate for NO synthase, NOS) results
      in increased NO generation and decreased CO production compared to control
      stimulation. On the other hand, application of the NOS inhibitor, l-N(G)
      nitroarginine methyl ester (l-NAME), results in decreased NO release but
      increased CO production of greater magnitude. This observation suggests that the
      interaction between NO and CO release is likely not linear and yet, they are
      tightly linked vasodilators. 

PMID- 25751505
TI  - Applying the World Health Organization Mental Health Action Plan to evaluate
      policy on addressing co-occurrence of physical and mental illnesses in Australia.
AB  - OBJECTIVES: The aim of the present study was to document Australian policies on
      the physical health of people with mental illness and evaluate the capacity of
      policy to support health needs. METHODS: A search of state and federal policies
      on mental and physical illness was conducted, as well as detailed analysis of
      policy content and the relationships between policies, by applying the World
      Health Organization Mental Health Action Plan 2013-2020 as an evaluative
      framework. RESULTS: National policy attention to the physical health of people
      with mental illness has grown, but there is little interconnection at the
      national and state levels. State policies across the country are inconsistent,
      and there is little evidence of consistent policy implementation. CONCLUSIONS: A
      coherent national health policy framework on addressing co-occurring physical and
      mental illnesses that includes healthcare system reforms and ensuring the
      interconnectedness of other relevant services should be prioritised.

PMID- 25751506
TI  - Safety and immunogenicity of influenza whole inactivated virus vaccines: A phase
      I randomized clinical trial.
AB  - BACKGROUND: Influenza vaccine production capacity is still insufficient to meet
      global demand in case of a pandemic. To expand worldwide influenza vaccine
      production capacity, a solid and transferable egg-based influenza vaccine
      production process was established that is suitable for upscaling and technology
      transfer to vaccine manufacturers in low- and middle-income countries. As a proof
      of-concept, the safety and immunogenicity of a pandemic whole inactivated virus
      (WIV) vaccine (H5N1) and a monovalent seasonal WIV vaccine (H3N2) were evaluated
      in a phase I clinical trial in adults. METHODS: Subjects were vaccinated with 2
      doses of pandemic WIV vaccine (pWIV), or one dose of either seasonal WIV vaccine
      (sWIV) or a commercially available trivalent comparator vaccine followed by a
      placebo dose. Haemagglutination inhibiting antibody titres against the influenza
      strains were determined before and 21 d after each vaccination. RESULTS: The
      frequency and severity of adverse reactions were comparable between groups. No
      serious adverse events were reported. After a single dose of sWIV the
      seroconversion rate was 91% (Committee for Proprietary Medicinal Products (CPMP)
      criterion >40%), the seroprotection rate was 100% (CPMP criterion >70%), and the
      mean geometric mean titre (GMT) increase was 24.9 (CPMP criterion >2.5). After
      two doses of pWIV, seroconversion rate and seroprotection rate were both 71%, and
      the mean GMT increase was 7.8. CONCLUSIONS: Both pWIV and sWIV were equally well
      tolerated as the comparator vaccine, and both vaccines complied with all 3 CPMP
      criteria. EudraCT 2011-000159-17. Netherlands National Trial Register 2695.

PMID- 25751507
TI  - Membrane Technologies in Wine Industry: An Overview.
AB  - Membrane processes are increasingly reported for various applications in wine
      industry such as microfiltration, electrodialysis, and reverse osmosis, but also
      emerging processes as bipolar electrodialysis and membrane contactor. Membrane
      based processes are playing a critical role in the field of
      separation/purification, clarification, stabilization, concentration, and de
      alcoholization of wine products. They begin to be an integral part of the
      winemaking process. This review will provide an overview of recent developments,
      applications, and published literature in membrane technologies applied in wine
      industry. 

PMID- 25751508
TI  - 2-Deoxyglucose induces cell cycle arrest and apoptosisin colorectal cancer cells
      independent of its glycolysis inhibition.
AB  - 2-Deoxyglucose (2DG) is an anticancer drug with excellent safety profile. Because
      of its higher dose requirements, its potential is yet to translate into a
      monotherapy. However, recently, 2DG has been tested as an adjunct in established
      chemotherapeutic regimens. 2DG enhanced the potency of several chemotherapeutic
      agents but not all. The rationale selection of known chemotherapeutic agents to
      use with 2DG is hampered because of the lack of complete understanding of
      mechanism behind 2DG anticancer effects. Although, 2DG is a well-known glycolytic
      inhibitor, which inhibits the key glycolytic enzyme hexokinase, its anticancer
      effects cannot be fully explained by this simplistic mechanism alone. In this
      article, we have shown for the first time that 2DG induced a transient expression
      of p21 and a continuous expression of p53 in colorectal cancer cells (SW620). The
      treatment also caused cell cycle arrest at G0/G1 phase and induced apoptosis
      through the mitochondrial pathway. The effects of 2DG on p21 and p53 protein
      levels were totally independent of its inhibitory effect on either hexokinase or
      ATP levels. Results from this study provides key insights into novel molecular
      mechanisms of 2DG and directs rational selection of other anticancer drugs to
      combine with 2DG in colorectal cancer treatment.

PMID- 25751509
TI  - Genes, brains, and behavior: imaging genetics for neuropsychiatric disorders.
AB  - The majority of neuropsychiatric disorders show a strong degree of heritability,
      yet little is known about molecular factors involved in the pathophysiology of
      diseases like schizophrenia. After a brief historical introduction into the
      current understanding of neuropsychiatric disorders, the aim of this study is to
      discuss imaging genetics as a strategy to explore the pathophysiology of
      neuropsychiatric disorders. The candidate gene approach of imaging genetics is
      used for validation/replication studies of genes, whereas the hypothesis-free,
      noncandidate gene approach appears to be a tool for gene discovery. Besides,
      integration of environmental factors into neuroimaging begins to converge on
      neuroimaging studies of genetic variation. In the light of data from other
      avenues such as animal experimentation, these developments show a model of
      interdisciplinary research, which may lead to identifying markers for
      neuropsychiatric disorders. 

PMID- 25751510
TI  - The Number of Cysteine Residues per Mole in Apolipoprotein E Is Associated With
      the Severity of PTSD Re-Experiencing Symptoms.
AB  - Apolipoprotien E (ApoE) is involved in critical neural functions and is
      associated with various neuropsychiatric disorders. ApoE exists in three isoforms
      that differ in the number of cysteine residues per mole (CysR/mole). This study
      evaluated associations between this informative ordinal biochemical scale
      (CysR/mole) and symptom severity in veterans with posttraumatic stress disorder
      (PTSD) or subthreshold PTSD. Results demonstrated a significant negative
      relationship between the CysR/mole and severity of PTSD re-experiencing symptoms,
      adjusted for trauma. The findings suggest a genetic influence on PTSD
      symptomatology and dovetail with recent advances regarding the molecular
      mechanisms underlying the differential effects of ApoE in the brain. 

PMID- 25751511
TI  - Neural evidence for compromised mental imagery in individuals with chronic
      schizophrenia.
AB  - Mental imagery impairment has been reported in schizophrenia. The present study
      aimed to investigate the neural evidence for mental imagery impairment in
      patients with schizophrenia. The study participants included 20 patients with
      chronic schizophrenia and 18 healthy control subjects. Event-related potentials
      were recorded during a mental hand rotation task, in which participants were
      instructed to judge the laterality of hands displayed in different orientations.
      The performances of patients were significantly less accurate and slower than
      control subjects on hand rotation task. Moreover, the patients showed
      significantly reduced rotation-related negativity amplitude for mental rotation
      effect. The results demonstrate mental imagery impairment in patients with
      schizophrenia at both the behavioral and neural levels. 

PMID- 25751513
TI  - Varying coefficient meta-analysis methods for odds ratios and risk ratios.
AB  - Odds ratios and risk ratios are useful measures of effect size in 2-group studies
      in which the response variable is dichotomous. Confidence interval methods are
      proposed for combining and comparing odds ratios and risk ratios in multistudy
      designs. Unlike the traditional fixed-effect meta-analysis methods, the proposed
      varying coefficient methods do not require effect-size homogeneity, and unlike
      the random-effects meta-analysis methods, the proposed varying coefficient
      methods do not assume that the effect sizes from the selected studies represent a
      random sample from a normally distributed superpopulation of effect sizes. The
      results of extensive simulation studies suggest that the proposed varying
      coefficient methods have excellent performance characteristics under realistic
      conditions and should provide useful alternatives to the currently used meta
      analysis methods. (PsycINFO Database Record 

PMID- 25751512
TI  - Vegetarian dietary patterns and the risk of colorectal cancers.
AB  - IMPORTANCE: Colorectal cancers are a leading cause of cancer mortality, and their
      primary prevention by diet is highly desirable. The relationship of vegetarian
      dietary patterns to colorectal cancer risk is not well established. OBJECTIVE: To
      evaluate the association between vegetarian dietary patterns and incident
      colorectal cancers. DESIGN, SETTING, AND PARTICIPANTS: The Adventist Health Study
      2 (AHS-2) is a large, prospective, North American cohort trial including 96,354
      Seventh-Day Adventist men and women recruited between January 1, 2002, and
      December 31, 2007. Follow-up varied by state and was indicated by the cancer
      registry linkage dates. Of these participants, an analytic sample of 77,659
      remained after exclusions. Analysis was conducted using Cox proportional hazards
      regression, controlling for important demographic and lifestyle confounders. The
      analysis was conducted between June 1, 2014, and October 20, 2014. EXPOSURES:
      Diet was assessed at baseline by a validated quantitative food frequency
      questionnaire and categorized into 4 vegetarian dietary patterns (vegan, lacto
      ovo vegetarian, pescovegetarian, and semivegetarian) and a nonvegetarian dietary
      pattern. MAIN OUTCOMES AND MEASURES: The relationship between dietary patterns
      and incident cancers of the colon and rectum; colorectal cancer cases were
      identified primarily by state cancer registry linkages. RESULTS: During a mean
      follow-up of 7.3 years, 380 cases of colon cancer and 110 cases of rectal cancer
      were documented. The adjusted hazard ratios (HRs) in all vegetarians combined vs
      nonvegetarians were 0.78 (95% CI, 0.64-0.95) for all colorectal cancers, 0.81
      (95% CI, 0.65-1.00) for colon cancer, and 0.71 (95% CI, 0.47-1.06) for rectal
      cancer. The adjusted HR for colorectal cancer in vegans was 0.84 (95% CI, 0.59
      1.19); in lacto-ovo vegetarians, 0.82 (95% CI, 0.65-1.02); in pescovegetarians,
      0.57 (95% CI, 0.40-0.82); and in semivegetarians, 0.92 (95% CI, 0.62-1.37)
      compared with nonvegetarians. Effect estimates were similar for men and women and
      for black and nonblack individuals. CONCLUSIONS AND RELEVANCE: Vegetarian diets
      are associated with an overall lower incidence of colorectal cancers.
      Pescovegetarians in particular have a much lower risk compared with
      nonvegetarians. If such associations are causal, they may be important for
      primary prevention of colorectal cancers.

PMID- 25751514
TI  - Structural equation modeling versus marginal structural modeling for assessing
      mediation in the presence of posttreatment confounding.
AB  - Inverse probability weighting for marginal structural models has been suggested
      as a strategy to estimate the direct effect of a treatment or exposure on an
      outcome in studies where the effect of mediator on outcome is subject to
      posttreatment confounding. This type of confounding, whereby confounders of the
      effect of mediator on outcome are themselves affected by the exposure,
      complicates mediation analyses and necessitates apt analysis strategies. In this
      article, we contrast the inverse probability weighting approach with the
      traditional path analysis approach to mediation analysis. We show that in a
      particular class of linear models, adjustment for posttreatment confounding can
      be realized via a fairly standard modification of the traditional path analysis
      approach. The resulting approach is simpler; by avoiding inverse probability
      weighting, it moreover results in direct effect estimators with smaller finite
      sample bias and greater precision. We further show that a particular variant of
      the G-estimation approach from the causal inference literature is equivalent with
      the path analysis approach in simple linear settings but is more generally
      applicable in settings with interactions and/or noncontinuous mediators and
      confounders. We conclude that the use of inverse probability weighting for
      marginal structural models to adjust for posttreatment confounding in mediation
      analysis is primarily indicated in nonlinear models for the outcome.

PMID- 25751515
TI  - Direction of effects in mediation analysis.
AB  - Data collected in the social sciences are rarely normally distributed. The linear
      regression methods that are usually employed to test mediation hypotheses
      consider moments no higher than second order. Recently discussed methods of
      direction dependence do consider higher moments. After a review of commonly used
      methods for mediation analysis, the present article demonstrates that these
      methods do not allow one to make decisions about competing mediation models, that
      is, models in which the reverse flow of causality is considered. Then, direction
      of dependence methodology is introduced which allows one to evaluate hypotheses
      of direction of effects, and extend its application to mediation analysis.
      Significance tests for statistical inference on direction of effects are proposed
      and discussed. Results of a Monte-Carlo simulation of the performance of the
      tests under various data scenarios are presented. An empirical example from
      research on intimate partner violence is given. Finally, possible limitations of
      these methods are addressed, issues of implicit assumptions concerning the origin
      of observed skewness are discussed, and the new methodology is embedded into the
      larger framework of causal inference.

PMID- 25751517
TI  - The misnomer of attention-deficit hyperactivity disorder.
AB  - We propose that attention-deficit disorder represents an inefficiency of an
      integrated system designed to allocate working memory to designated tasks rather
      than the absence or dysfunction of a particular form of attention. A significant
      portion of this inefficiency in the allocation of working memory represents poor
      engagement of the reward circuit with distinct circuits of learning and
      performance that control instrumental conditioning (learning). Efficient
      attention requires the interaction of these circuits. For a significant
      percentage of individuals who present with attention-deficit disorder, their
      problems represent the engagement, or lack thereof, of the motivational and
      reward circuit as opposed to problems, or disorders of attention traditionally
      defined as problems with orienting, focusing, and sustaining. We demonstrate that
      there is an integrated system of working-memory allocation that responds by
      recruiting relevant aspects of both cortex and subcortex to the demands of the
      task being encountered. In this model, attention is viewed as a gating function
      determined by novelty, flight-or-fight response, and reward history/valence
      affecting motivation. We view the traditional models of attention, rather than
      describe specific types of attention per se, as representing the description of
      the behavioral output of this integrated orienting and engagement system designed
      to allocate working memory to task-specific stimuli. 

PMID- 25751516
TI  - Upward synaptic scaling is dependent on neurotransmission rather than spiking.
AB  - Homeostatic plasticity encompasses a set of mechanisms that are thought to
      stabilize firing rates in neural circuits. The most widely studied form of
      homeostatic plasticity is upward synaptic scaling (upscaling), characterized by a
      multiplicative increase in the strength of excitatory synaptic inputs to a neuron
      as a compensatory response to chronic reductions in firing rate. While reduced
      spiking is thought to trigger upscaling, an alternative possibility is that
      reduced glutamatergic transmission generates this plasticity directly. However,
      spiking and neurotransmission are tightly coupled, so it has been difficult to
      determine their independent roles in the scaling process. Here we combined
      chronic multielectrode recording, closed-loop optogenetic stimulation, and
      pharmacology to show that reduced glutamatergic transmission directly triggers
      cell-wide synaptic upscaling. This work highlights the importance of synaptic
      activity in initiating signalling cascades that mediate upscaling. Moreover, our
      findings challenge the prevailing view that upscaling functions to
      homeostatically stabilize firing rates. 

PMID- 25751519
TI  - Youth suicide and access to guns.

PMID- 25751518
TI  - Distinct human stem cell populations in small and large intestine.
AB  - The intestine is composed of an epithelial layer containing rapidly proliferating
      cells that mature into two regions, the small and the large intestine. Although
      previous studies have identified stem cells as the cell-of-origin for intestinal
      epithelial cells, no studies have directly compared stem cells derived from these
      anatomically distinct regions. Here, we examine intrinsic differences between
      primary epithelial cells isolated from human fetal small and large intestine,
      after in vitro expansion, using the Wnt agonist R-spondin 2. We utilized flow
      cytometry, fluorescence-activated cell sorting, gene expression analysis and a
      three-dimensional in vitro differentiation assay to characterize their stem cell
      properties. We identified stem cell markers that separate subpopulations of
      colony-forming cells in the small and large intestine and revealed important
      differences in differentiation, proliferation and disease pathways using gene
      expression analysis. Single cells from small and large intestine cultures formed
      organoids that reflect the distinct cellular hierarchy found in vivo and respond
      differently to identical exogenous cues. Our characterization identified numerous
      differences between small and large intestine epithelial stem cells suggesting
      possible connections to intestinal disease. 

PMID- 25751522
TI  - Deep brain stimulation for Parkinson disease in elderly individuals.

PMID- 25751523
TI  - Deep brain stimulation for Parkinson disease in elderly individuals.

PMID- 25751524
TI  - Deep brain stimulation for Parkinson disease in elderly individuals-reply.

PMID- 25751525
TI  - Arsenic speciation in rice by capillary electrophoresis/inductively coupled
      plasma mass spectrometry: enzyme-assisted water-phase microwave digestion.
AB  - We report an analytical methodology for the quantification of common arsenic
      species in rice and rice cereal using capillary electrophoresis coupled with
      inductively coupled plasma mass spectrometry (CE-ICPMS). An enzyme (i.e., alpha
      amylase)-assisted water-phase microwave extraction procedure was used to extract
      four common arsenic species, including dimethylarsinic acid (DMA),
      monomethylarsonic acid (MMA), arsenite [As(III)], and arsenate [As(V)] from the
      rice matrices. The addition of the enzyme alpha-amylase during the extraction
      process was necessary to reduce the sample viscosity, which subsequently
      increased the injection volume and enhanced the signal response. o-Arsanilic acid
      (o-ASA) was added to the sample solution as a mobility marker and internal
      standard. The obtained repeatability [i.e., relative standard deviation (RSD %)]
      of the four arsenic analytes of interest was less than 1.23% for elution time and
      2.91% for peak area. The detection limits were determined to be 0.15-0.27 ng g(
      1). Rice standard reference materials SRM 1568b and CRM 7503-a were used to
      validate this method. The quantitative concentrations of each organic arsenic and
      summed inorganic arsenic were found within 5% difference of the certified values
      of the two reference materials.

PMID- 25751526
TI  - Quantitative SHINERS analysis of temporal changes in the passive layer at a gold
      electrode surface in a thiosulfate solution.
AB  - Shell-isolated gold nanoparticles (SHINs) were employed to record shell-isolated
      nanoparticle-enhanced Raman spectra (SHINERS) of a passive layer formed at a gold
      surface during gold leaching from thiosulfate solutions. The (3
      aminopropyl)triethoxysilane (APTES) and a sodium silicate solution were used to
      coat gold nanoparticles with a protective silica layer. This protective silica
      layer prevented interactions between the thiosulfate electrolyte and the gold
      core of the SHINs when the SHINs-modified gold electrode was immersed into the
      thiosulfate lixiviant. The SHINERS spectra of the passive layer, formed from
      thiosulfate decomposition, contained bands indicative of hydrolyzed APTES. We
      have demonstrated how to exploit the presence of these APTES bands as an internal
      standard to compensate for fluctuations of the surface enhancement of the
      electric field of the photon. We have also developed a procedure that allows for
      removal of the interfering APTES bands from the SHINERS spectra. These
      methodological advancements have enabled us to identify the species forming the
      passive layer and to determine that the formation of elemental sulfur, cyclo-S8,
      and polymeric sulfur chains is responsible for inhibition of gold dissolution in
      oxygen rich thiosulfate solutions. 

PMID- 25751527
TI  - When push comes to shove: unravelling the mechanism and scope of nonemissive meso
      unsaturated BODIPY dyes.
AB  - We report herein spectroscopy and computational results that illustrate an
      efficient intramolecular deactivation pathway for meso-unsaturated boron
      dipyrromethene (BODIPY) dyes in their singlet excited state. Our results show
      that the mechanism hinges on the structural flexibility imparted by the boron
      atom and on the energetic stabilization conferred by extending the conjugation
      into the meso substituent, which is otherwise unconjugated in the ground state.
      Following photoexcitation, rotation along the dihedral angle of the meso
      unsaturated group results in its conjugation at the expense of shifting one
      pyrrole moiety in dipyrrin out of the plane. Internal conversion to an
      energetically hot, ground-state species efficiently competes with emission. The
      mechanism applies to meso-vinyl, -formyl, and -iminyl moieties. The presence of
      methyl groups at positions C1 and C7 exacerbates the energetic penalty toward
      conjugation of the meso groups leading to a small energy gap between relaxed
      excited state and ground state and undetected emission quantum yields.
      Importantly, methyls at C1 and C7 prevent nonradiative deactivation in meso-aryl
      moieties, illustrating that when push comes to shove, the energetic (kinetic)
      barrier toward reaching conjugation is too large for aryl moieties but low enough
      for smaller groups to effectively compete with radiative transitions. Wisely
      chosen meso-unsaturated BODIPY dyes may serve as richly sensitive platforms for
      the preparation of novel fluorogenic substrates to monitor chemical reactions or
      to probe the rigidity of their surrounding environment. 

PMID- 25751528
TI  - Cost evaluation of reproductive and primary health care mobile service delivery
      for women in two rural districts in South Africa.
AB  - BACKGROUND: Cervical cancer screening is a critical health service that is often
      unavailable to women in under-resourced settings. In order to expand access to
      this and other reproductive and primary health care services, a South African non
      governmental organization established a van-based mobile clinic in two rural
      districts in South Africa. To inform policy and budgeting, we conducted a cost
      evaluation of this service delivery model. METHODS: The evaluation was
      retrospective (October 2012-September 2013 for one district and April-September
      2013 for the second district) and conducted from a provider cost perspective.
      Services evaluated included cervical cancer screening, HIV counselling and
      testing, syndromic management of sexually transmitted infections (STIs), breast
      exams, provision of condoms, contraceptives, and general health education. Fixed
      costs, including vehicle purchase and conversion, equipment, operating costs and
      mobile clinic staffing, were collected from program records and public sector
      pricing information. The number of women accessing different services was
      multiplied by ingredients-based variable costs, reflecting the consumables
      required. All costs are reported in 2013 USD. RESULTS: Fixed costs accounted for
      most of the total annual costs of the mobile clinics (85% and 94% for the two
      districts); the largest contributor to annual fixed costs was staff salaries.
      Average costs per patient were driven by the total number of patients seen, at
      $46.09 and $76.03 for the two districts. Variable costs for Pap smears were
      higher than for other services provided, and some services, such as breast exams
      and STI and tuberculosis symptoms screening, had no marginal cost. CONCLUSIONS:
      Staffing costs are the largest component of providing mobile health services to
      rural communities. Yet, in remote areas where patient volumes do not exceed
      nursing staff capacity, incorporating multiple services within a cervical cancer
      screening program is an approach to potentially expand access to health care
      without added costs.

PMID- 25751531
TI  - Somatostatin cells regulate sensory response fidelity via subtractive inhibition
      in olfactory cortex.
AB  - Diverse types of local GABAergic interneurons shape the cortical representation
      of sensory information. Here we show how somatostatin-expressing interneurons
      (SOM cells) contribute to odor coding in mouse olfactory cortex. We find that
      odor-tuned SOM cells regulate principal cells through a purely subtractive
      operation that is independent of odor identity or intensity. This operation
      enhances the salience of odor-evoked activity without changing cortical odor
      tuning. SOM cells inhibit both principal cells and fast-spiking interneurons,
      indicating that subtractive inhibition reflects the interplay of multiple classes
      of interneurons.

PMID- 25751532
TI  - The dorsal posterior insula subserves a fundamental role in human pain.
AB  - Several brain regions have been implicated in human painful experiences, but none
      have been proven to be specific to pain. We exploited arterial spin-labeling
      quantitative perfusion imaging and a newly developed procedure to identify a
      specific role for the dorsal posterior insula (dpIns) in pain. Tract tracing
      studies in animals identify a similar region as fundamental to nociception, which
      suggests the dpIns is its human homolog and, as such, a potential therapeutic
      target.

PMID- 25751533
TI  - Explicit memory creation during sleep demonstrates a causal role of place cells
      in navigation.
AB  - Hippocampal place cells assemblies are believed to support the cognitive map, and
      their reactivations during sleep are thought to be involved in spatial memory
      consolidation. By triggering intracranial rewarding stimulations by place cell
      spikes during sleep, we induced an explicit memory trace, leading to a goal
      directed behavior toward the place field. This demonstrates that place cells'
      activity during sleep still conveys relevant spatial information and that this
      activity is functionally significant for navigation.

PMID- 25751535
TI  - Dynamics of nitric oxide synthase-calmodulin interactions at physiological
      calcium concentrations.
AB  - The intracellular Ca2+ concentration is an important regulator of many cellular
      functions. The small acidic protein calmodulin (CaM) serves as a Ca2+ sensor and
      control element for many enzymes. Nitric oxide synthase (NOS) is one of the
      proteins that is activated by CaM and plays a major role in a number of key
      physiological and pathological processes. Previous studies have shown CaM to act
      like a switch that causes a conformational change in NOS to allow for the
      electron transfer between the reductase and oxygenase domains through a process
      that is thought to be highly dynamic. We have analyzed the structure and dynamics
      of complexes formed by peptides based on inducible NOS (iNOS) and endothelial NOS
      (eNOS) with CaM at Ca2+ concentrations that mimic the physiological basal (17 and
      100 nM) and elevated levels (225 nM) found in mammalian cells using fluorescence
      techniques and nuclear magnetic resonance spectroscopy. The results show the CaM
      NOS complexes have similar structures at physiological and fully saturated Ca2+
      levels; however, their dynamics are remarkably different. At 225 nM Ca2+, the CaM
      NOS complexes show overall an increase in backbone dynamics, when compared to the
      dynamics of the complexes at saturating Ca2+ concentrations. Specifically, the N
      lobe of CaM in the CaM-iNOS complex displays a lower internal mobility (higher
      S2) and higher exchange protection compared to those of the CaM-eNOS complex. In
      contrast, the C-lobe of CaM in the CaM-eNOS complex is less dynamic. These
      results illustrate that structures of CaM-NOS complexes determined at saturated
      Ca2+ concentrations cannot provide a complete picture because the differences in
      intramolecular dynamics become visible only at physiological Ca2+ levels.

PMID- 25751536
TI  - Young people's perceptions of sexual and reproductive health in regional and
      rural Queensland: capturing the views of adolescents through reference groups and
      a user-friendly electronic survey.
AB  - Background Young people in regional and rural Queensland have difficulty
      accessing sexual and reproductive health (SRH) services. Young people's views
      regarding barriers and enablers for accessing SRH services and markers of quality
      are largely unknown. METHODS: Young people's perceptions regarding SRH services
      are explored through a cross-sectional study via eight reference group meetings
      and an electronic survey in four sites: Atherton Tablelands, Rockhampton,
      Toowoomba and Townsville. The survey, developed in consultation with young
      people, was administered online and face to face using tablet computers. Data
      from 391 rural and regional participants was precoded for bivariate comparisons
      involving chi(2) and confidence interval (CI) tests. RESULTS: The most valued
      markers of quality in SRH services defined by young people all related to staff
      characteristics. Young people preferred services where staff were friendly
      (87.3%; 95% CI: 83.8-90.8%), easy to talk to (91.4%; 95% CI: 88.5-94.3%), good
      listeners (95.4%; 95% CI: 93.2-97.6%) and did not judge them (90.5%; 95% CI: 87.4
      93.6%). A model of SRH service delivery encompassed within general health
      services was highly valued by 58.9% (95% CI 53.7-64.1%). However, 36.2% (95% CI:
      31.4-41.0%) preferred to seek care from SRH specialist services. CONCLUSIONS:
      Service provision can be improved by training, and retaining friendly, attentive
      and non-judgemental staff. A model of service provision that includes general
      health care and provides sexual health services may increase the acceptability
      and accessibility of SRH services among youth. Additionally, our study highlights
      the need for choice between general and specialist SRH services.

PMID- 25751534
TI  - NPY signaling inhibits extended amygdala CRF neurons to suppress binge alcohol
      drinking.
AB  - Binge alcohol drinking is a tremendous public health problem because it leads to
      the development of numerous pathologies, including alcohol abuse and anxiety. It
      is thought to do so by hijacking brain systems that regulate stress and reward,
      including neuropeptide Y (NPY) and corticotropin-releasing factor (CRF). The
      central actions of NPY and CRF have opposing functions in the regulation of
      emotional and reward-seeking behaviors; thus, dysfunctional interactions between
      these peptidergic systems could be involved in the development of these
      pathologies. We used converging physiological, pharmacological and chemogenetic
      approaches to identify a precise neural mechanism in the bed nucleus of the stria
      terminalis (BNST), a limbic brain region involved in pathological reward and
      anxiety behaviors, underlying the interactions between NPY and CRF in the
      regulation of binge alcohol drinking in both mice and monkeys. We found that NPY
      Y1 receptor (Y1R) activation in the BNST suppressed binge alcohol drinking by
      enhancing inhibitory synaptic transmission specifically in CRF neurons via a
      previously unknown Gi-mediated, PKA-dependent postsynaptic mechanism.
      Furthermore, chronic alcohol drinking led to persistent alterations in Y1R
      function in the BNST of both mice and monkeys, highlighting the enduring,
      conserved nature of this effect across mammalian species. Together, these data
      provide both a cellular locus and signaling framework for the development of new
      therapeutics for treatment of neuropsychiatric diseases, including alcohol use
      disorders.

PMID- 25751537
TI  - Highly efficient synthesis of HIV NNRTI doravirine.
AB  - The development of an efficient and robust process for the production of HIV
      NNRTI doravirine is described. The synthesis features a continuous aldol reaction
      as part of a de novo synthesis of the key pyridone fragment. Conditions for the
      continuous flow aldol reaction were derived using microbatch snapshots of the
      flow process. 

PMID- 25751538
TI  - An overview of a novel, water-soluble undenatured type II collagen (NEXT-II).
AB  - BACKGROUND: Osteoarthritis, the most common form of arthritis, is a crippling,
      chronic debilitating bone disease that commonly affects humans, dogs, and horses.
      Inflammation and inflammatory responses are key factors for causing swelling,
      redness, pain, and loss of movement in arthritic animals and humans. METHODS AND
      RESULTS: We developed a novel, water-soluble, undenatured type II collagen (NEXT
      II) for osteoarthritis. NEXT-II demonstrated broad-spectrum safety and
      nonmutagenicity. NEXT-II exhibited significant efficacy in ameliorating pain and
      inflammation in collagen-induced arthritis in mice. NEXT-II enhanced the
      proportion of CD4+CD25+T cells, and gene expressions of stimulated dendritic
      cells induced markers for regulatory T cell such as forkhead box p3, transforming
      growth factor-beta1, and CD25. Furthermore, NEXT-II was assessed in moderately
      arthritic dogs receiving either placebo or 10 mg NEXT-II over a period of 150
      days. NEXT-II exhibited a significant reduction in overall pain, pain after limb
      manipulation, and pain after physical exertion compared to the control dogs.
      Physical health and serum chemistry (alanine aminotransferase, blood urea
      nitrogen, and creatine kinase) were not altered when these arthritic dogs were
      treated over a period of 150 days. CONCLUSIONS: These results demonstrate the
      broad-spectrum safety and efficacy of NEXT-II in ameliorating the symptoms of
      arthritis. Key Teaching Points: *A novel, water-soluble, undenatured type II
      collagen (NEXT-II) was developed for osteoarthritis. *The safety studies
      including acute oral and dermal toxicity, primary dermal and primary eye
      irritation, Ames' bacterial reverse mutation assay, mouse lymphoma assay, and 150
      day long-term safety studies were conducted. *NEXT-II exhibited significant
      efficacy in ameliorating pain and inflammation in collagen-induced arthritis in
      mice. *NEXT-II exhibited a significant reduction in overall pain in moderately
      arthritic dogs without changing physical parameters.

PMID- 25751539
TI  - Individual differences in the effect of orthographic/phonological conflict on
      rhyme and spelling decisions.
AB  - In typical readers, orthographic knowledge has been shown to influence
      phonological decisions. In the present study, we used visual rhyme and spelling
      tasks to investigate the interaction of orthographic and phonological information
      in adults with varying reading skill. Word pairs that shared both orthography and
      phonology (e.g., throat/boat), differed in both orthography and phonology (e.g.,
      snow/arm), shared only orthography (e.g., farm/warm), and shared only phonology
      (e.g., vote/boat) were visually presented to university students who varied in
      reading ability. For rhyme judgment, participants were slower and less accurate
      to accept rhyming pairs when words were spelled differently and to reject non
      rhyming pairs when words were spelled similarly. Similarly, for spelling
      judgments, participants were slower and less accurate when indicating that word
      endings were spelled differently when words rhymed, and slower and less accurate
      when indicating that words were spelled similarly when words did not rhyme.
      Crucially, while these effects were clear at the group level, there were large
      individual differences in the extent to which participants were impacted by
      conflict. In two separate samples, reading skill was associated with the extent
      to which orthographic conflict impacted rhyme decisions such that individuals
      with better nonword reading performance were less impacted by orthographic
      conflict. Thus, university students with poorer reading skills may differ from
      their peers either in the reading strategies they use or in the degree to which
      they automatically access word form information. Understanding these
      relationships is important for understanding the roles that reading processes
      play in readers of different skill. 

PMID- 25751540
TI  - Nanoscale morphology of multilayer PbTe/CdTe heterostructures and its effect on
      photoluminescence properties.
AB  - We study nanoscale morphology of PbTe/CdTe multilayer heterostuctures grown by
      molecular beam epitaxy on hybrid GaAs/CdTe (100) substrates. Nominally, the
      structures consist of 25 repetitions of subsequently deposited CdTe and PbTe
      layers with comparable thicknesses of 21 and 8 nm, respectively. However, the
      morphology of the resulting structures crucially depends on the growth
      temperature. The two-dimensional layered, superlattice-like character of the
      structures remains preserved only when grown at low substrate temperatures, such
      as 230  degrees C. The samples grown at the slightly elevated temperature of 270 
      degrees C undergo a morphological transformation to structures consisting of CdTe
      and PbTe pillars and columns oriented perpendicular to the substrate. Although
      the pillar-like objects are of various shapes and dimensions these structures
      exhibit exceptionally strong photoluminescence in the near infrared spectral
      region. At the higher growth temperature of 310  degrees C, PbTe and CdTe
      separate completely forming thick layers oriented longitudinally to the substrate
      plane. The observed topological transformations are driven by thermally activated
      atomic diffusion in the solid state phase. The solid state phase remains fully
      coherent during the processes. The observed topological transitions leading to
      the material separation in PbTe/CdTe system could be regarded as an analog of
      spinodal decomposition of an immiscible solid state solution and thus they can be
      qualitatively described by the Cahn-Hillard model as proposed by Groiss et al
      (2014 APL Mater. 2 012105). 

PMID- 25751541
TI  - Targeting PI3K-p110alpha Suppresses Influenza Virus Infection in Chronic
      Obstructive Pulmonary Disease.
AB  - RATIONALE: Chronic obstructive pulmonary disease (COPD) and influenza virus
      infections are major global health issues. Patients with COPD are more
      susceptible to infection, which exacerbates their condition and increases
      morbidity and mortality. The mechanisms of increased susceptibility remain poorly
      understood, and current preventions and treatments have substantial limitations.
      OBJECTIVES: To characterize the mechanisms of increased susceptibility to
      influenza virus infection in COPD and the potential for therapeutic targeting.
      METHODS: We used a combination of primary bronchial epithelial cells (pBECs) from
      COPD and healthy control subjects, a mouse model of cigarette smoke-induced
      experimental COPD, and influenza infection. The role of the phosphoinositide-3
      kinase (PI3K) pathway was characterized using molecular methods, and its
      potential for targeting assessed using inhibitors. MEASUREMENTS AND MAIN RESULTS:
      COPD pBECs were susceptible to increased viral entry and replication. Infected
      mice with experimental COPD also had more severe infection (increased viral titer
      and pulmonary inflammation, and compromised lung function). These processes were
      associated with impaired antiviral immunity, reduced retinoic acid-inducible gene
      I, and IFN/cytokine and chemokine responses. Increased PI3K-p110alpha levels and
      activity in COPD pBECs and/or mice were responsible for increased infection and
      reduced antiviral responses. Global PI3K, specific therapeutic p110alpha
      inhibitors, or exogenous IFN-beta restored protective antiviral responses,
      suppressed infection, and improved lung function. CONCLUSIONS: The increased
      susceptibility of individuals with COPD to influenza likely results from impaired
      antiviral responses, which are mediated by increased PI3K-p110alpha activity.
      This pathway may be targeted therapeutically in COPD, or in healthy individuals,
      during seasonal or pandemic outbreaks to prevent and/or treat influenza.

PMID- 25751542
TI  - Vascular access creation and maintenance in the USA.
AB  - Exponential growth and increasing longevity of end-stage renal disease (ESRD) has
      resulted in significant ongoing changes in vascular access (VA) planning and
      management in the United States. There is a positive trend showing an increase in
      arteriovenous fistula (AVF) prevalence both in incident and prevalent patients
      and a decrease in tunneled dialysis catheters (TDCs) in prevalent patients.
      Current surgical training seems to provide adequate exposure to VA and an ample
      opportunity to develop skills required for safe surgical placement of VA. The
      prevalent differences in practice patterns suggest a need for standardization of
      VA care. There is a need for a structured curriculum in VA, which is a critical
      component in making sound decisions in access planning and management. 

PMID- 25751543
TI  - UK organisation of access care.
AB  - National UK audits show that 73% of patients start renal replacement therapy
      (RRT) with haemodialysis (HD). However, 59% of those start HD on non-permanent
      access in the form of a tunnelled line (TL) or a non-tunnelled line (NTL), 40% on
      an arteriovenous fistula (AVF) and 1% on an arteriovenous graft (AVG). After 3
      months, the number of patients dialysing on AVF was only 41%. Late referrals,
      within 90 days of starting dialysis to the renal service, occur in one-fifth of
      all incident HD patients. Referral to a surgeon was an important determinant of
      mode of access at first dialysis. However, referral to a surgeon occurred in 67%
      of patients who were known to the nephrologist for over a year and in 46% of
      patients who were known to nephrology less than a year but more than 90 days.
      Best practice tariffs of the National Health Service (NHS) payment by results
      program have set a target of 75% of prevalent HD occurring via an AVF or AVG in
      2011/2012, rising to 85% in 2013/2014. We suggest that this target is best
      achieved by increasing timely referral to a surgeon for creation of access before
      HD is needed. 

PMID- 25751544
TI  - Hemodialysis vascular access management in the Netherlands.
AB  - PURPOSE: In the Netherlands, 86% of patients start renal replacement therapy with
      chronic intermittent hemodialysis (HD). Guidelines do indicate predialysis care
      and maintenance of a well-functioning vascular access (VA) as critical issues in
      the management of the renal failure patient. Referral to the surgeon and time to
      VA creation are important determinants of the type and success of the VA and HD
      treatment. METHODS AND RESULTS: Data from a national questionnaire showed that
      time from referral to the surgeon and actual access creation is <4 weeks in 43%,
      4 to 8 weeks in 30% and >8 weeks in 27% of the centers. Preoperative
      ultrasonography and postoperative access flowmetry are the diagnostic methods in
      the majority of centers (98%). Most facilities perform rope-ladder cannulation
      with occasionally the buttonhole technique for selected patients in 87% of the
      dialysis units. Endovascular intervention for thrombosis is practiced by 13%,
      surgical thrombectomy by 21% and either endovascular or surgery by 66% of the
      centers. Weekly multidisciplinary meetings are organized in 57% of the units.
      Central vein catheters are inserted by radiologists (36%), nephrologists and
      surgeons (32%). CONCLUSIONS: We conclude that guidelines implementation has been
      successful in particular regarding issues as preoperative patient assessment for
      VA creation and postoperative surveillance in combination with (preemptive)
      endovascular intervention, leading to very acceptable VA thrombosis rates.

PMID- 25751545
TI  - Vascular access creation and care should be provided by nephrologists.
AB  - The long-term survival and quality of life of patients on hemodialysis is
      dependent on the adequacy of dialysis via an appropriately placed vascular
      access. Recent clinical practice guidelines recommend the creation of native
      arteriovenous fistula or synthetic graft before start of chronic hemodialysis
      therapy to prevent the need for complication-prone dialysis catheters. The direct
      involvement of nephrologists in the management of referral patterns, predialysis
      follow-up, policy of venous preservation, preoperative evaluation, vascular
      access surgery and vascular access care seems to be important and productive
      targets for the quality of care delivered to the patients with end-stage renal
      disease. Early referral to nephrologists is important for delay progression of
      both kidney disease and its complications by specific and adequate treatment, for
      education program which should include modification of lifestyle, medication
      management, selection of treatment modality and instruction for vein preservation
      and vascular access. Nephrologists are responsible for on-time placement and
      adequate maturation of vascular access. The number of nephrologists around the
      world who create their own fistulas and grafts is growing, driven by a need for
      better patient outcomes on hemodialysis. Nephrologists have also a key role for
      care of vascular access during hemodialysis treatment by following vascular
      access function using clinical data, physical examination and additional
      ultrasound evaluation. Timely detection of malfunctioning vascular access means
      timely surgical or radiological intervention and increases the survival of
      vascular access. 

PMID- 25751546
TI  - Organisation of a radiological vascular access unit.
AB  - An interventional vascular access unit is usually part of an interdisciplinary
      centre, including departments of nephrology, vascular surgery, angiology and
      interventional radiology. We present recommendations on quality control,
      equipment and diagnostic and interventional techniques for the treatment of
      vascular access insufficiency. 

PMID- 25751547
TI  - Brachiocephalic and basilic fistula.
AB  - INTRODUCTION: Brescia-Cimino radiocephalic arteriovenous fistula (AVF) remains
      the first choice vascular access procedure for patients in need of long-term
      hemodialysis. Brachiocephalic fistulas are considered as a secondary option in
      almost all published guidelines. Recently in many reports, elbow and upper arm
      fistulas are recommended to be used as primary fistulas especially in elderly,
      diabetic, hypertensive patients. Elbow fistulas (brachiocephalic and
      brachiobasilic) should only rarely be constructed as primary fistulas. Forearm
      AVFs should be tried first to give a chance to the patient, because it is not the
      maturation-patency rates per se but also lowering the complication rates and
      saving the vessels for future use are equally important. BACKGROUND: The average
      life expectancy of patients receiving hemodialysis has increased in recent years
      and many patients now live longer and require secondary or tertiary procedures.
      CONCLUSIONS: When forearm fistulas have failed, brachiocephalic AVF is usually
      preferred first, because of cephalic vein's appropriate anatomy for easy
      cannulation and ease of the operation. Operative procedure is less invasive
      compared to brachiobasilic AVF, therefore BC should be the procedure of choice
      when both veins are available.

PMID- 25751548
TI  - Upper limb grafts for hemodialysis access.
AB  - Arteriovenous (AV) grafts are required for hemodialysis access when options for
      native fistulas have been fully exhausted, where they continue to play an
      important role in hemodialysis patients, offering a better alternative to central
      vein catheters. When planning autogenous accesses using Doppler ultrasound,
      adequate arterial inflow and venous outflow must be consciously preserved for
      future access creation with grafts. Efforts to improve graft patency include
      changing graft configuration, graft biology and hemodynamics. Industry offers
      early cannulation grafts to reduce central catheter use and a bioengineered graft
      is undergoing clinical studies. Although the outcome of AV grafts is inferior to
      fistulas, grafts can provide long-term hemodialysis access that is a better
      alternative to central venous catheters. AV grafts have significant drawbacks,
      mainly poor patency, infection and cost but also have some advantages: early
      maturation, ease of creation and needling and widespread availability. The
      outcome of AV graft surgery is variable from center to center. The primary
      patency rate for AV grafts is 58% at 6 months and the secondary patency rate is
      76% at 6 months and 55% at 18 months. There are centers of excellence that report
      a 1 year secondary patency rate of up to 91%. In this review of the use of AV
      grafts for hemodialysis access in the upper extremities, technical issues
      involved in planning the access and performing the surgery in its different
      configurations are discussed and the role of surveillance and maintenance with
      their attendant surgical and radiological interventions is described. 

PMID- 25751549
TI  - Promises for the future: minimally invasive fistula creation.
AB  - The surgical creation of an autogenous fistula is the vascular access of choice
      for delivery of hemodialysis. However, it is prone to relatively high rates of
      maturation failure, stenosis and thrombosis. Most of these problems can be
      attributed to the surgical creation itself. Percutaneous or endovascular creation
      of an autogenous fistula offers the possibility of overcoming some of these
      problems. 

PMID- 25751550
TI  - Is there an association between central vein stenosis and line infection in
      patients with tunnelled central venous catheters (TCVCs)?
AB  - PURPOSE: Central vein stenosis (CVS) and line infection are well-recognized
      complications of tunnelled central venous catheters (TCVCs) in patients on
      haemodialysis. The aim of this study was to evaluate any relationship between CVS
      and line infection. METHODS: Analysis of 500 consecutive patients undergoing TCVC
      insertion was undertaken. Data were collected on patient demographics, details of
      line insertion and duration, culture-proven bacteraemia and presence of
      symptomatic CVS. Logistic regression analysis was used to determine risk factors
      for CVS and bacteraemia. RESULTS: Mean patient age was 59.0 years (range: 17-93).
      Mean number of catheter days was 961.1 +/- 57.6 per TCVC; 39.4% of TCVCs were
      associated with culture-proven bacteraemia and 23.6% developed symptomatic CVS.
      Bacteraemia and CVS were inevitable complications of all TCVCs. The time to
      symptomatic CVS was longer in patients with bacteraemia than without (1230.91 +/-
      101.29 vs. 677.49 +/- 61.59 days, p<0.001). Patients who had early infection
      within 90 days of TCVC insertion were less likely to develop CVS (5.9% vs. 22.8%,
      p<0.001). There was no difference in the bacteraemia rate per 1,000 catheter days
      between patients with and without CVS (2.62 +/- 1.41 vs. 2.35 +/- 0.51; p =
      0.98). Number of line days (odds ratio (OR) 1.02, p = 0.003), age (OR 1.04, p =
      0.04) and culture-proven line infection (OR 0.59, p = 0.014) were all
      independently associated with CVS. CONCLUSIONS: Our results suggest that early
      line infection may be protective against CVS. Alternatively, there may be two
      distinct predisposition states for CVS and line infection. Further studies are
      needed to confirm our association and investigate causation.

PMID- 25751551
TI  - New technology: heparin and antimicrobial-coated catheters.
AB  - Although tunneled hemodialysis catheter must be considered the last option for
      vascular access, it is necessary in some circumstances in the dialysis patient.
      Thrombosis and infections are the main causes of catheter-related comorbidity.
      Fibrin sheath, intimately related with the biofilm, is the precipitating factor
      of this environment, determining catheter patency and patient morbidity. Its
      association with bacterial overgrowth and thrombosis has led to the search of
      multiple preventive measures. Among them is the development of catheter coatings
      to prevent thrombosis and infections. There are two kinds of treatments to cover
      the catheter surface: antithrombotic and antimicrobial coatings. In nondialysis
      related settings, mainly in intensive care units, both have been shown to be
      efficient in the prevention of catheter-related infection. This includes heparin,
      silver, chlorhexidine, rifampicine and minocycline. In hemodialysis population,
      however, few studies on surface-treated catheters have been made and they do not
      provide evidence that shows complication reduction. The higher effectiveness of
      coatings in nontunneled catheters may depend on the short average life of these
      devices. Hemodialysis catheters need to be used over long periods of time and
      require clinical trials to show effectiveness of coatings over long periods. This
      also means greater knowledge of biofilm etiopathogeny and fibrin sheath
      development. 

PMID- 25751552
TI  - Update on cannulation techniques.
AB  - There are two methods of fistula cannulation for hemodialysis. The first,
      different site or rope-ladder cannulation method, established by originators of
      the arteriovenous fistula as a blood access for hemodialysis in 1966, relies on
      changing the puncture sites for each dialysis. The second, constant site or
      buttonhole method, developed several years later, recommends using the same
      puncture sites for consecutive dialyses. The first method is prevailing at
      present, but the second method is becoming more and more popular. The major
      advantage of this buttonhole method is lower cannulation pain, fewer fistula
      complications, with the exception of fistula infection, which is more common in
      some studies. This method is more difficult and requires experienced single
      cannulator to establish good puncture sites. Home hemodialysis patients using
      single cannulator, the patient or helper, have better results with this method.
      Busy dialysis centers with high rotation of cannulators do not have as good
      results and prefer the rope-ladder method. 

PMID- 25751553
TI  - Influence of drugs on arteriovenous vascular access dysfunction.
AB  - Vascular access dysfunction, due to venous stenosis at the vein-artery
      anastomosis in arteriovenous fistulas and vein-graft anastomosis in synthetic
      arteriovenous grafts, is a major cause of morbidity and mortality in dialysis
      patients. The two overarching approaches to prevent and treat vascular access
      dysfunction are from systemic or local (including endovascular and perivascular)
      routes. However, there are currently very few effective therapies to treat
      vascular access dysfunction. This article will review major studies evaluating
      systemic, endovascular, and perivascular therapies for vascular access
      dysfunction. Ongoing research to evaluate novel innovations to prevent and/or
      manage vascular access dysfunction appears promising. 

PMID- 25751554
TI  - Balloon angioplasty for low-flow access.
AB  - The common mechanism for low access flow is intimal hyperplasia leading to
      stenosis within the access circuit. Balloon angioplasty (percutaneous
      transluminal angioplasty, PTA) remains the mainstay of treatment despite multiple
      technologies introduced in the past. New technologies continue to be introduced
      in an effort to improve on outcomes of angioplasty. This article briefly reviews
      the use of and outcomes of PTA, technologies, past, present and future as well as
      some of the questions that remain unanswered with PTA. 

PMID- 25751555
TI  - Type of peritoneal dialysis catheter and outcomes.
AB  - In peritoneal dialysis (PD), a well-functioning catheter is of great importance,
      because a dysfunctional catheter may be associated with incidence of peritonitis,
      efficiency of dialysis, and to the overall quality of treatment, representing one
      of the main barriers to optimal use of PD. When considering the relationship
      between PD catheter type and outcomes, we should keep in mind the different types
      of available PD catheters, those that are most commonly used in clinical
      practice, and the available head-to-head comparisons in the literature. The main
      differences in PD catheter design include the number of cuffs, the shape of
      subcutaneous tract (straight vs. swan neck), and the shape of intraperitoneal
      tract (straight vs. coiled). The availability of the best catheter design and
      materials, along with a skillful management of PD access, may have the greatest
      impact on long-term patient outcome on PD. It is now established that the use of
      straight catheters may improve outcomes and technique survival, but further
      advances in PD catheter technology can potentially improve technique survival.
      The self-locating PD catheter is a well established device that has not been
      fully studied and it may represent, based on the available observational evidence
      and on the clinical experience, an already existing technological advance
      deserving further studies.

PMID- 25751556
TI  - Neurological complications of vascular access.
AB  - Neurological problems are common in patients undergoing haemodialysis. Over 60%
      of patients will suffer from symptoms of underlying polyneuropathy due to uraemia
      or diabetes. Others will have subclinical disease demonstrable by nerve
      conduction studies. Nerve injury following haemodialysis access surgery is
      underreported. However, sensory nerve lesions are probably common after most
      vascular access procedures but are rarely debilitating. Nerve compression
      syndromes such as carpal tunnel and ulnar compression syndromes are common,
      especially in patients who have been on dialysis for some years and at least some
      of these are related to or exacerbated by the access. Recognition is essential as
      they are eminently treatable by decompression surgery. Tourniquet use appears to
      be safe for carpal tunnel or ulnar nerve decompression surgery. Ischaemic
      monomelic neuropathy (IMN) is rare but follows a period of ischaemia during or as
      a result of access surgery, most commonly to construct a brachial arteriovenous
      fistula or graft. It is characterised by intense pain, out of proportion to any
      ischaemia, involves all of the upper limb nerves and may progress to involve the
      motor nerves eventually resulting in a useless clawed hand. It requires prompt
      treatment of any residual ischaemia after access creation, if necessary by access
      ligation, as in the established syndrome, like the even rarer complication of
      reflex sympathetic dystrophy, it is very difficult to offer any useful treatment
      other than symptomatic relief and physiotherapy.

PMID- 25751557
TI  - Arteriovenous graft configuration in hemodialysis: does it matter?
AB  - PURPOSE: The current guidelines for arteriovenous graft (AVG) configuration in
      hemodialysis state the following sequence: forearm loop, upper arm straight or
      curved and upper arm looped. These recommendations are based upon literature from
      the 1980s. Modern patient demographics and patient treatment algorithms, i.e.,
      the Fistula First initiative (FFI), have greatly changed the current practice
      environment. It is not clear if these changes alter the outcomes of AVGs based
      upon configuration. METHODS: The most recent National Kidney Foundation Kidney
      Disease Outcomes Quality Initiative (NKF/K-DOQI) guidelines for vascular access
      were reviewed. Articles cited to support recommendations for AVG configuration
      were evaluated. The following search terms: arteriovenous graft configuration,
      access configuration, PTFE configuration in hemodialysis and straight, looped,
      curved graft configuration were used to search PubMed, Ovid, Medline and Google
      scholar. Articles that included data comparing AVG configuration were included.
      Citations within those articles were examined for publications overlooked in the
      initial search. Four articles and one abstract were reviewed and separated into
      pre- and post-FFI groups. RESULTS: Pre-FFI articles demonstrate superiority of
      forearm looped AVG over straight forearm grafts. Post-FFI, the literature
      suggests that primary patency, thrombosis and steal are not affected by
      configuration and location, although looped configuration may have superior
      secondary patency. CONCLUSIONS: The available literature is mixed regarding the
      effect of configuration on AVG outcomes. Current studies illustrate the effect
      may be limited and that larger randomized controlled trials are necessary to draw
      firm conclusions. Regardless, adequate inflow and an appropriately sized outflow
      vein are paramount for optimal graft performance.

PMID- 25751558
TI  - Long-term results of biological grafts for haemodialysis vascular access.
AB  - The quest for suitable conduits for dialysis access has continued since the first
      patients were dialysed. Whilst synthetic grafts made from expanded
      polytetrafluoroethylene (ePTFE) have been the main definitive option after
      autologous arteriovenous fistulas they have a number of drawbacks, which has led
      to the use and development of biological grafts such as autografts, homografts or
      xenografts. Technology continues to improve and currently biosynthetic options
      are available which may combine the benefits of a readily available product
      without the drawbacks of PTFE. The history and evidence of biological options for
      haemodialysis access are discussed. 

PMID- 25751559
TI  - Long-term results of PTFE grafts.
AB  - Vascular surgeons are essential in "lifeline" creation for hemodialysis patients
      and should be the central player in any multidisciplinary access service together
      with nephrologists, dialysis staff and interventional radiology. In this
      position, access surgeons are involved in complicated clinical decision making
      regarding primary and secondary access selection, which throughout the last
      decade has been largely aided, and influenced, by national and international
      guidelines as well as other initiatives. These recommendations, unanimously and
      appropriately, advocate the placement of native fistulas over synthetic grafts
      (the majority grafts from expanded polytetrafluoroethylene, ePTFE, herein
      referred to as PTFE) based on the superiority of fistulas with respect to
      complications such as infections and thrombosis. Nevertheless, the use of PTFE
      grafts for hemodialysis access is an accepted and firmly established alternative
      to native fistulas where data today reveal unwanted consequences to
      overinterpretation of established guidelines such as increased catheter use. This
      information highlights a need for an adjustment of access selection strategies
      based on patient-centered algorithms. Here, available results on PTFE graft
      performance in hemodialysis access is recapitulated, with respect to both
      conventional grafts and technical modifications, and conclude with a modified
      approach to primary access selection. 

PMID- 25751560
TI  - Revision techniques for failed PD catheters: outcome in a University Hospital.
AB  - PURPOSE: A disfunctioning peritoneal dialysis (PD) catheter has been reported in
      upto 35%. We report different salvage techniques used and its outcome. METHODS:
      We retrospectively reviewed our database on PD patients from 2009 to 2014.
      Operational data and data on PD catheter function were checked. RESULTS: From
      2009 to 2014, we operated on 32 patients. Malfunction of their PD catheter was
      found in 23 patients and hernias in nine patients. Different laparoscopic
      techniques were used, including reposition of the catheter, fixation of the
      catheter, removal of adhesions and omentectomy. Of these 23 patients, 18 (78%)
      had a normal functioning catheter after the operation. Nine patients of the total
      of 32 patients had a correction of their hernia. In all cases, a non-absorbable
      mesh was used. Of those nine patients with a hernia, eight (89%) had a normal
      functioning catheter after the procedure. CONCLUSIONS: The salvage of the
      catheter by means of a laparoscopic procedure or correction of a hernia is
      worthwhile and can save up to 81% of the catheters.

PMID- 25751561
TI  - One-year efficacy of the RUDI technique for flow reduction in high-flow
      autologous brachial artery-based hemodialysis vascular access.
AB  - PURPOSE: Flow reduction is advised in hemodialysis (HD) patients with a high-flow
      (>2 L/min) arteriovenous fistula (AVF). The revision using distal inflow (RUDI)
      technique is based on the premise that access flow is attenuated once inflow is
      provided by a smaller caliber forearm artery. Aim of the study was to evaluate
      the efficacy of RUDI during a 1-year follow-up. METHODS: All HD patients
      undergoing a RUDI operation using a greater saphenous vein (GSV) or a basilic
      vein (BaV) interposition for a high-flow access (HFA, >2 L/min) during a 3.5-year
      time period were included. Serial access flow, percentage of freedom from
      recurrent high flow and complications were determined. RESULTS: A total of 19 HFA
      patients were studied (11 males, age 55 +/- 3 years). All AVFs were brachial
      artery based (brachiocephalic, n = 14; brachiobasilic, n = 5). RUDI immediately
      reduced access flow by almost 2 L/min (3,080 +/- 200 to 1,170 +/- 160 mL/min (p =
      0.001)). Access flows at 1, 6 and 12 months were 1,150 +/- 160, 1,460 +/- 200 and
      1,580 +/- 260 mL/min, respectively. Postoperative complications included
      insufficient flow reduction (n = 1, BaV) and occlusion requiring revision (n = 1,
      GSV). Recurrent HFA occurred three times (n = 2 BaV, n = 1 GSV). Access flows
      were significantly (p<0.05) higher in the BaV group compared to the GSV group.
      CONCLUSIONS: RUDI effectively reduces access flow in a brachial artery-based high
      flow HD vascular access. A flow-reducing effect is sustained at 1-year follow-up
      in most patients. GSV is preferred as an interposition graft compared to a BaV.

PMID- 25751562
TI  - Intervention for access-induced ischemia: which option is the best?
AB  - INTRODUCTION: Access-induced ischemia is a rare but important surgical
      complication with potentially devastating long-term results. The question remains
      which therapeutic option is the best for the different forms of ischemia. METHOD:
      A review of the literature concerning access-induced ischemia (classification,
      treatment) was performed; furthermore, our own experience of more than 300 cases
      with ischemia was discussed. RESULTS: There are four different stages of dialysis
      access-induced ischemia syndrome (DAIIS) that need adequate treatment: stage I
      conservatively, stage II fistula banding, stage III proximalization operation or
      distal revascularization interval ligation and stage IV closure of the access.
      DISCUSSION: According to the many publications and to our own experience, there
      are good therapeutic options for many of the patients with DAIIS. However, in
      case of extended lesions/gangrene, closure of the access should be discussed in
      time before major amputation becomes necessary.

PMID- 25751563
TI  - Transposition, elevation, lipectomy and V-Wing for easy needling.
AB  - PURPOSE: The purpose of this study is to report surgical techniques to facilitate
      cannulation of deep matured veins. METHODS AND RESULTS: 1) Basilic vein tunnel
      superficialization with rerouting in an anterior tunnel is mandatory for brachial
      basilic arteriovenous fistula (AVF), mostly performed in a second surgical stage.
      The elevation technique, which could necessitate cannulation of the vein through
      the overlying scar, is not advisable. 2) Femoral vein superficialization is a one
      stage surgical operation. Complications of this high-flow AVF are distal ischemia
      (diabetes and occlusive arterial disease are contraindications), iliac vein
      stenosis due to intimal hypertrophy and cardiac issues. Nevertheless, we have
      achieved high long-term patency rates (N = 70). Primary patency rates at 1 and 9
      years were 91% +/- 4% and 45% +/- 11%, respectively. Secondary patency rates at 1
      and 9 years were 84% +/- 5% and 56% +/- 9%, respectively. 3) Lipectomy for
      superficialization of the forearm radial-cephalic AVF is described for obese
      patients. Subcutaneous tissues are resected using two transverse incisions.
      Mobilization of the vein is avoided. At 3 years (N = 49), we recorded 63% +/- 8%
      and 88% +/- 7% primary and secondary patency rates, respectively. Anterior
      transposition of the forearm basilic vein is not necessary when using
      microsurgery for creation of distal ulno-basilic AVF. 4) VWING is a novel
      surgically implanted device to help buttonhole technique cannulation. It is too
      early to draw any conclusion from the preliminary published reports. CONCLUSIONS:
      Tunnel-transposition and lipectomy are efficient techniques to allow easy
      needling of deeply situated upper-arm basilic vein, and cephalic vein in obese
      patients, respectively.

PMID- 25751564
TI  - Key points for patient safety in dialysis access.
AB  - For more than 15 years, patient safety has been an issue in different domains of
      medicine. There is evidence for this subject and also a great need for
      information. First, we should be familiar with the basic terminology such as the
      relationship between adverse events and errors, and understand the variations of
      error. In patient management, besides skills and knowledge (evidence-based
      medicine), the ability (competence) of healthcare professionals to act and react
      in unexpected situations is key to prevent and treat adverse events. Not only
      healthcare professionals should be involved in the process but also healthy
      people in a way that they understand and patients in a way that they are actively
      involved. This paper will show how a more general view of patient safety can and
      should be implemented in the daily work of caregivers dealing with dialysis
      access in different aspects. A key factor to advance in this subject is to be
      open-minded and sensualized for this topic. The reader should get an idea of how
      an institution can create a culture of safety. 

PMID- 25751565
TI  - Patient safety: the doctor's perspective.
AB  - Medical errors can be defined as the failure of a planned action to be completed
      as intended or the use of a wrong plan to achieve an aim. Beyond their economic
      cost and their cost in human lives, errors cause loss of trust in the healthcare
      system by patients and diminished satisfaction by both patients and health
      professionals. There are many evidence-based safety-oriented behaviours and
      interventions that are easily implemented, such as ultrasound-guided central
      venous catheter insertion, prevention of catheter-related bloodstream infection
      and more. In vascular access, the development of research in patient safety has
      raised a variety of issues requiring study in order to provide the optimal
      patient safety approach. Patients are major contributors to their own safety, and
      as such, physicians should develop a new approach to involve them in the cycle of
      decision making through every step of their treatment. There are many
      opportunities along this path for the patient to be engaged in safety behaviours
      and for the access team to ensure such behaviours by employing simple strategies.
      The advent of the access centre, based on multidisciplinary teamwork, has
      enhanced the potential to improve patient safety by prevention of errors in
      planning and performing access surgery, avoiding delay in treatment of access
      malfunction and improving communication between the team members. However, a
      significant effort in research is still needed in order to implement intervention
      by evidence-based data focused on patient safety. 

PMID- 25751566
TI  - Simulation in vascular access surgery training.
AB  - Rapidly growing technical developments and working time constraints call for
      changes in trainee formation. In reality, trainees spend fewer hours in the
      hospital and face more difficulties in acquiring the required qualifications in
      order to work independently as a specialist. Simulation-based training is a
      potential solution. It offers the possibility to learn basic technical skills,
      repeatedly perform key steps in procedures and simulate challenging scenarios in
      team training. Patients are not at risk and learning curves can be shortened.
      Advanced learners are able to train rare complications. Senior faculty member's
      presence is key to assess and debrief effective simulation training. In the field
      of vascular access surgery, simulation models are available for open as well as
      endovascular procedures. In this narrative review, we describe the theory of
      simulation, present simulation models in vascular (access) surgery, discuss the
      possible benefits for patient safety and the difficulties of implementing
      simulation in training.

PMID- 25751567
TI  - Fertility after intrauterine device removal: a pilot study.
AB  - BACKGROUND: Despite high efficacy, only 7.7% of women in the United States
      currently using contraception use an IUD. There is little published contemporary
      data about fertility rates after IUD use, especially in nulliparous women and
      women using the hormonal IUD. STUDY DESIGN: We recruited sexually active women 18
      to 35 years of age enrolled in the Contraceptive CHOICE Project who had
      discontinued a contraceptive method and desired pregnancy. RESULTS: In this pilot
      project, we enrolled 69 former IUD users (19 copper and 50 levonorgestrel) and 42
      former non-IUD users. Pregnancy rates at 12 months were similar between the two
      groups; 81% of IUD users became pregnant compared to 70% of non-IUD users (p =
      0.18). In the Cox model, there was no difference in the time to pregnancy in IUD
      users compared to non-IUD users (HRadj 1.19, 95% CI 0.74-1.92). African American
      race was the only variable associated with reduced fertility (HRadj 0.40, 95% CI
      0.24-0.67). CONCLUSIONS: We found no difference in 12-month pregnancy rates or
      time to pregnancy between former IUD users and users of other contraceptive
      methods. However, there was a clinically and statistically significant reduction
      in fertility in African American women.

PMID- 25751569
TI  - Transient absorption dynamics of sterically congested Cu(I) MLCT excited states.
AB  - Subpicosecond through supra-nanosecond transient absorption dynamics of the
      homoleptic Cu(I) metal-to-ligand charge transfer (MLCT) photosensitizers
      including the benchmark [Cu(dmp)2](+) (dmp =2,9-dimethyl-1,10-phenanthroline)
      chromophore, as well as [Cu(dsbp)2](+) (dsbp =2,9-di(sec-butyl)-1,10
      phenanthroline and [Cu(dsbtmp)2](+) (dsbtmp =2,9-di(sec-butyl)-3,4,7,8
      tetramethyl-1,10-phenanthroline) were investigated in dichloromethane and
      tetrahydrofuran solutions. Visible and near-IR spectroelectrochemical
      measurements of the singly reduced [Cu(dsbp)2](+) and [Cu(dsbtmp)2](+) species
      were determined in tetrahydrofuran, allowing for the identification of redox
      specific phenanthroline-based radical anion spectroscopic signatures prevalent in
      the respective transient absorption experiments. This study utilized four
      different excitation wavelengths (418, 470, 500, and 530 nm) to elucidate
      dynamics on ultrafast times scales spanning probe wavelengths ranging from the UV
      to the near-IR (350 to 1450 nm). With the current time resolution of ~150 fs,
      initial excited state decay in all three compounds was found to be independent of
      excitation wavelength. Not surprisingly, there was little to no observed
      influence of solvent in the initial stages of excited state decay in any of these
      molecules including [Cu(dmp)2](+), consistent with results from previous
      investigators. The combined experimental data revealed two ranges of time
      constants observed on short time scales in all three MLCT chromophores and both
      components lengthen as a function of structure in the following manner:
      [Cu(dsbtmp)2](+) < [Cu(dsbp)2](+) < [Cu(dmp)2](+). The molecule with the most
      inhibited potential for distortion, [Cu(dsbtmp)2](+), possessed the fastest
      ultrafast dynamics as well as the longest excited state lifetimes in both
      solvents. These results are consistent with a small degree of excited state
      distortion, rapid intersystem crossing, and weak vibronic coupling to the ground
      state. The concomitant systematic variation in both initial time constants,
      assigned to pseudo-Jahn-Teller distortion and intersystem crossing, suggest that
      both processes are intimately coupled in all molecules in the series. The
      variability in these time scales illustrate that strongly impeded structural
      distortion in Cu(I) MLCT excited state enables more rapid surface crossings in
      the initial deactivation dynamics. 

PMID- 25751568
TI  - Is Pseudoexfoliation Syndrome a Risk Factor for Cerebro Vascular Disease?
AB  - PURPOSE: To determine the relationship between cerebro vascular disease and
      pseudoexfoliation syndrome. MATERIALS AND METHODS: This cross-sectional case
      control study consisted of 50 patients with ischemic-type cerebro vascular
      disease and 50 control subjects. All subjects were investigated for diabetes
      mellitus and hypertension status and underwent a detailed ophthalmic examination.
      A diagnosis of pseudoexfoliation syndrome was made if characteristic greyish
      particulate matter was found on the anterior lens capsule after pupillary
      dilatation by slit-lamp examination. All subjects were compared in terms of
      pseudoexfoliation syndrome, diabetes mellitus, and hypertension. Pearson Chi
      Square and Student's t test were used for statistical analysis. Logistic
      regression analyses of the risk factors between groups were also made. RESULTS:
      The presence of pseudoexfoliation syndrome was significantly higher in patients
      with cerebro vascular disease when compared to the control subjects (p = 0.02).
      The frequency of diabetes mellitus was similar between the two groups. Arterial
      hypertension was significantly more frequent in the patient group when compared
      to the control subjects (p < 0.01). The logistic regression analysis showed that
      both pseudoexfoliation syndrome and hypertension were significantly associated
      with cerebro vascular disease. CONCLUSION: In the present study, we found that
      pseudoexfoliation syndrome frequency was found to be higher in patients with
      cerebro vascular disease than in control subjects. A slit-lamp examination of the
      eye could be an important marker that indicates the risk of cerebro vascular
      disease. We recommend an evaluation of all subjects with pseudoexfoliation
      syndrome for the presence of cerebro vascular disease. Longitudinal studies with
      larger populations are needed to confirm this relationship.

PMID- 25751570
TI  - Sex chromosome evolution: life, death and repetitive DNA.
AB  - Dimorphic sex chromosomes create problems. Males of many species, including
      Drosophila, are heterogametic, with dissimilar X and Y chromosomes. The essential
      process of dosage compensation modulates the expression of X-linked genes in one
      sex to maintain a constant ratio of X to autosomal expression. This involves the
      regulation of hundreds of dissimilar genes whose only shared property is
      chromosomal address. Drosophila males dosage compensate by up regulating X-linked
      genes 2 fold. This is achieved by the Male Specific Lethal (MSL) complex, which
      is recruited to genes on the X chromosome and modifies chromatin to increase
      expression. How the MSL complex is restricted to X-linked genes remains unknown.
      Recent studies of sex chromosome evolution have identified a central role for 2
      types of repetitive elements in X recognition. Helitrons carrying sites that
      recruit the MSL complex have expanded across the X chromosome in at least one
      Drosophila species. (1) Our laboratory found that siRNA from an X-linked
      satellite repeat promotes X recognition by a yet unknown mechanism. (2) The
      recurring adoption of repetitive elements as X-identify elements suggests that
      the large and mysterious fraction of the genome called "junk" DNA is actually
      instrumental in the evolution of sex chromosomes. 

PMID- 25751571
TI  - Hypoxic postconditioning reduces microglial activation, astrocyte and caspase
      activity, and inflammatory markers after hypoxia-ischemia in the neonatal rat
      brain.
AB  - BACKGROUND: Postconditioning (PostC) with mild hypoxia shortly after a neonatal
      hypoxic-ischemic (HI) brain injury can reduce brain damage, however, the
      mechanisms underlying this protection are not known. We hypothesize that hypoxic
      PostC reduces brain markers of glial activity, inflammation, and apoptosis
      following HI injury. METHODS: Sprague Dawley rat pups were exposed to right
      common carotid artery occlusion and hypoxia (7% oxygen, 3 h) on postnatal day 7
      and 24 h later, pups were exposed to hypoxic PostC (8% O2 for 1 h/day for 5 d) or
      kept at ambient conditions for the same duration. HI+N pups demonstrated ~10%
      loss in ipsilateral brain tissue which was rescued with HI+PostC. To investigate
      the cellular responses, markers of astrocytes, microglia, inflammation, and
      caspase 3 activity were examined using immunohistochemistry and enzyme-linked
      immunosorbent assay. RESULTS: PostC reduced the area of astrocyte staining
      compared to HI+N. There was also a shift in microglial morphology toward a primed
      state in both PostC groups. Protein levels of interleukin-1beta and caspase 3
      were elevated in HI+N brains and reduced by PostC. CONCLUSION: This is the first
      demonstration that PostC can reduce glial activity, inflammatory mediators, and
      cell death after a neonatal HI brain injury.

PMID- 25751572
TI  - Dexmedetomidine reduces cranial temperature in hypothermic neonatal rats.
AB  - BACKGROUND: The alpha2-adrenergic agonist dexmedetomidine (DEX) is increasingly
      used for prolonged sedation of critically ill neonates, but there are currently
      no data evaluating possible consequences of prolonged neonatal DEX exposure. We
      evaluated the pharmacokinetics and histological consequences of neonatal DEX
      exposure. METHODS: DEX was administered (s.c.) to naive (uninjured) neonatal
      Lewis rats to provide acute (25 ug/kg, *1) or prolonged (25 ug/kg three times
      daily, *2 or *4 d) exposure. Therapeutic hypothermia was simulated using a water
      cooled blanket. Cranial temperatures were measured using an infrared thermometer.
      DEX concentrations were measured by LC-MS in plasma and homogenized brainstem
      tissue for pharmacokinetic analysis. Cortex, cerebellum, and brainstem were
      evaluated for evidence of inflammation or injury. RESULTS: Prolonged neonatal DEX
      exposure was not associated with renal or brain pathology or indices of gliosis,
      macrophage activation, or apoptosis in either hypothermic or control rats. Plasma
      and brain DEX concentrations were tightly correlated. DEX peaked within 15 min in
      brain and reduced cranial temperature from 32 to 30  degrees C within 30 min
      after injection in cooled rats. CONCLUSION: Prolonged DEX treatment in neonatal
      rats was not associated with abnormal brain histology. These data provide
      reassuring preliminary results for using DEX with therapeutic hypothermia to
      treat near-term brain injury.

PMID- 25751573
TI  - Genetic polymorphisms of heme-oxygenase 1 (HO-1) may impact on acute kidney
      injury, bronchopulmonary dysplasia, and mortality in premature infants.
AB  - BACKGROUND: Heme oxygenase 1 (HO1) catalyzes heme degradation, and offers
      protection for several organs, including the kidney. Genetic polymorphisms of HO
      1 are associated with poor clinical outcomes in several populations. METHODS: 
      POPULATION: We prospectively enrolled 117 premature infants (birth weight <=1,200
      g or postgestational age <=31 wk) and evaluated two DNA genetic variants proximal
      to the promoter region of HO-1 (GT(n) repeats, and -413T>A SNP). We evaluated how
      these polymorphisms affect two clinical outcomes: (i) Acute Kidney Injury (AKI)
      rise in serum creatinine (SCr) >= 0.3 mg/dl or >= 150-200% from lowest previous
      value, (ii) the composite of mortality and bronchopulmonary dysplasia (BPD)
      defined as receipt of oxygen at 36 wk postmenstrual age. RESULTS: AKI occurred in
      34/117 (29%) of neonates; 12/117 (10%) died; 29/105 (28%) survivors had BPD.
      Neonates with TT genotype at 413T>A before the HO-1 promoter had higher rates of
      AKI (P < 0.05). There was no difference in number of GT(n) repeats and clinical
      outcomes. CONCLUSION: We did not find an association between the GT(n) tandem
      repeat of HO-1 and AKI nor BPD/mortality. However, infants with TT genotype of
      the 413T>A genetic alteration had lower incidence of AKI. Further studies using
      larger cohorts are needed to better understand these relationships.

PMID- 25751575
TI  - Polyetheretherketone (PEEK) rods: short-term results in lumbar spine degenerative
      disease.
AB  - Pedicle screw and rod instrumentation has become the preferred technique for
      performing stabilization and fusion in the surgical treatment of lumbar spine
      degenerative disease. Rigid fixation leads to high fusion rates but may also
      contribute to stress shielding and adjacent segment degeneration. Thus, the use
      of semirigid rods made of polyetheretherketone (PEEK) has been proposed. Although
      the PEEK rods biomechanical properties, such as anterior load sharing properties,
      have been shown, there are few clinical studies evaluating their application in
      the lumbar spine surgical treatment. This study examined a retrospective cohort
      of patients who underwent posterior lumbar fusion for degenerative disease using
      PEEK rods, in order to evaluate the clinical and radiological outcomes and the
      incidence of complications. 

PMID- 25751574
TI  - Seroprevalence and Incidence of hepatitis E in blood donors in Upper Austria.
AB  - BACKGROUND: In recent years various studies showed, that hepatitis E virus (HEV)
      is a growing public health problem in many developed countries. Therefore, HEV
      infections might bear a transmission risk by blood transfusions. The clinical
      relevance still requires further investigations. The aim of this study was to
      provide an overview of acute HEV infections in Upper Austrian blood donors as
      well as a risk estimation of this transfusion-related infection. METHODS AND
      FINDINGS: A total of 58,915 blood donors were tested for HEV RNA using a
      commercial HEV RT-PCR Kit. 7 of these donors (0.01%) were PCR-positive with
      normal laboratory parameters in absence of clinical signs of hepatitis. Viral
      load determined by quantitative real-time PCR showed a HEV nucleic acid
      concentration of 2,217 293,635 IU/ml. At follow-up testing (2-11 weeks after
      donation) all blood donors had negative HEV RNA results. Additionally, genotyping
      was performed by amplification and sequencing of the ORF1 or ORF2 region of the
      HEV genome. All HEV RNA positive donor samples revealed a genotype 3 isolate. For
      the antibody screening, anti-HEV IgM and IgG were detected by ELISA. Follow up
      serological testing revealed that no donor was seropositive for HEV IgM or IgG
      antibodies at time of donation. Moreover, we verified the prevalence of anti-HEV
      IgG in 1,203 of the HEV RNA negative tested blood donors. Overall 13.55% showed
      positive results for anti-HEV IgG. CONCLUSIONS: In the presented study, we
      investigated HEV infections in blood donations of Upper Austria over 1 year. We
      concluded that 1 out of 8,416 blood donations is HEV RNA positive. Seroprevalence
      of anti HEV IgG results in an age-related increase of 13.55%. Therefore, based on
      this data, we recommend HEV-PCR screening to prevent transmission of hepatitis E
      virus by transfusion.

PMID- 25751576
TI  - Determining need for treatment in residual pituitary adenomas.
AB  - AIM: The optimal management of residual pituitary adenoma after resection is not
      clearly defined, with some authors proposing early radiosurgery or radiotherapy
      for patients with evidence of residual tumor on postoperative imaging and others
      recommending observation alone. This retrospective study seeks to determine the
      most appropriate treatment for patients with evidence of residual tumor on
      postoperative MRI. METHODS: Forty-one consecutive patients who underwent
      transsphenoidal resection of pituitary adenomas between 2002 and 2005 and were
      followed radiographically and clinically for a mean of 4.4 years were analyzed.
      RESULTS: Despite an official interpretation by a board-certified neuroradiologist
      suggesting the presence of residual tumor postoperatively in twenty-four out of
      forty-one patients, only four patients (16.7%) required additional intervention
      during the follow-up period. None of the patients received perioperative
      radiotherapy. CONCLUSION: This suggests that aggressive management of
      radiographically suspected residual tumor may not be indicated and that
      observation with serial imaging may be sufficient in the management of patients
      with residual tumor.

PMID- 25751577
TI  - The use of TachoSil(r) as dural sealant in intradural extramedullary tumors
      surgery.

PMID- 25751578
TI  - A randomized, placebo-controlled trial of the analgesic efficacy and safety of
      the p38 MAP kinase inhibitor, losmapimod, in patients with neuropathic pain from
      lumbosacral radiculopathy.
AB  - OBJECTIVES: Preclinical studies have demonstrated involvement of p38 mitogen
      activated protein kinase signaling pathways in the development of persistent pain
      after peripheral nerve injury. A double-blind, randomized, placebo-controlled
      study was undertaken to evaluate the analgesic efficacy of losmapimod (GW856553),
      a novel p38alpha/beta inhibitor, in patients with chronic neuropathic pain due to
      lumbosacral radiculopathy. MATERIALS AND METHODS: A total of 144 patients with at
      least moderate baseline pain intensity (average daily score of >=4 on an 11-point
      pain intensity numeric rating scale) were randomized to receive losmapimod, 7.5
      mg bid orally or placebo. All patients underwent a blinded placebo run-in period
      for 7 days before receiving losmapimod/placebo for 28 days. Efficacy and safety
      evaluations were undertaken weekly. RESULTS: The adjusted mean treatment
      difference for the change from baseline to week 4 in numeric rating scale was 
      0.36 U (95% confidence interval, -0.84, 0.13; P=0.149) in favor of losmapimod
      over placebo; this was not considered clinically meaningful. Statistically
      significant differences in favor of losmapimod were observed, however, for
      several secondary endpoints of emotional, physical, and social functioning:
      Oswestry Disability Index; Profile of Mood States total score; Short-Form 36
      Health Survey physical functioning, bodily pain, general health, role emotional,
      social functioning, and vitality domains; and Short-Form 36 physical, and mental
      components. There were no unexpected findings related to safety or tolerability
      following treatment with losmapimod. DISCUSSION: Losmapimod could not be
      differentiated from placebo in terms of analgesia. The lack of response could
      reflect insufficient losmapimod levels in the spinal cord or differences between
      lumbosacral radiculopathy and animal models of neuropathic pain.

PMID- 25751580
TI  - The effect of perceived burdensomeness and thwarted belongingness on therapists'
      assessment of patients' suicide risk.
AB  - OBJECTIVE: The interpersonal theory of suicide posits that perceived
      burdensomeness and thwarted belongingness are two causal interactive suicidal
      risk factors. The aim of this study was to examine whether therapists are
      affected by these factors upon assessing patients' suicide risk. METHOD: Using an
      experimental design, 388 mental health professionals were presented with a text
      vignette describing a hypothetical patient with either high or low perceived
      burdensomeness and with either high or low thwarted belongingness. RESULTS: The
      findings revealed that both factors affected therapists' risk assessment of
      psychache, suicidal ideation, suicide attempt and resilience. CONCLUSIONS: The
      study results highlight the interpersonal theory as an important theory for
      understanding the factors upon which therapists and mental health professionals
      rely when assessing suicide risk.

PMID- 25751579
TI  - Triggering HIV polyprotein processing by light using rapid photodegradation of a
      tight-binding protease inhibitor.
AB  - HIV protease (PR) is required for proteolytic maturation in the late phase of HIV
      replication and represents a prime therapeutic target. The regulation and
      kinetics of viral polyprotein processing and maturation are currently not
      understood in detail. Here we design, synthesize, validate and apply a potent,
      photodegradable HIV PR inhibitor to achieve synchronized induction of
      proteolysis. The compound exhibits subnanomolar inhibition in vitro. Its
      photolabile moiety is released on light irradiation, reducing the inhibitory
      potential by 4 orders of magnitude. We determine the structure of the PR
      inhibitor complex, analyze its photolytic products, and show that the enzymatic
      activity of inhibited PR can be fully restored on inhibitor photolysis. We also
      demonstrate that proteolysis of immature HIV particles produced in the presence
      of the inhibitor can be rapidly triggered by light enabling thus to analyze the
      timing, regulation and spatial requirements of viral processing in real time. 

PMID- 25751581
TI  - Hormonal diterpenoids derived from ent-kaurenoic acid are involved in the blue
      light avoidance response of Physcomitrella patens.
AB  - Gibberellins (GAs) are diterpenoid hormones that regulate growth and development
      in flowering plants. The moss Physcomitrella patens has part of the GA
      biosynthetic pathway from geranylgeranyl diphosphate to ent-kaurenoic acid via
      ent-kaurene, but it does not produce GA. Disruption of the ent-kaurene synthase
      gene in P. patens suppressed caulonemal differentiation. Application of ent
      kaurene or ent-kaurenoic acid restored differentiation, suggesting that
      derivative(s) of ent-kaurenoic acid, but not GAs, are endogenous regulator(s) of
      caulonemal cell differentiation. The protonemal growth of P. patens shows an
      avoidance response under unilateral blue light. Physiological studies using gene
      mutants involved in ent-kaurene biosynthesis confirmed that diterpenoid(s)
      regulate the blue-light response. Here, we discuss the implications of these
      findings, and provide data for the ent-kaurene oxidase gene-disrupted mutant. 

PMID- 25751585
TI  - Emergency room (ER) referrals and health insurance in the United States.
AB  - This article aims to determine how various health insurance policies affect the
      rate of emergency room (ER) referrals in the United States. The secondary data,
      gathered in National Health Measurement Study (NHMS) in 2008 and 2010, was used.
      The authors identify the relationships between health insurance and ER referrals
      by using zero-inflated binomial and zero-inflated Poisson regression. About 17%
      (2008) and 20% (2010) of the respondents had one or more ER referrals in the 2
      years; those who were under coverage of governmental health insurance are more
      likely to refer ER than uninsured group. The differences in ER referrals that
      ended with hospital admission across different insurance policies are not
      significant. Health insurance is a remarkable factor in ER referrals; the
      coverage of health insurance plans can affect consuming the services provided in
      ER. Governmental insurance plans can increase ER referrals. 

PMID- 25751586
TI  - Validation of the appropriate use criteria for coronary angiography: a cohort
      study.
AB  - BACKGROUND: The use of invasive coronary angiography in stable ischemic heart
      disease (IHD) varies widely. OBJECTIVE: To validate the 2012 appropriate use
      criteria for diagnostic catheterization by examining the relationship between the
      appropriateness of cardiac catheterization in patients with suspected stable IHD
      and the proportion of patients with obstructive coronary artery disease (CAD) and
      subsequent revascularization. DESIGN: Population-based, observational,
      multicenter cohort study. SETTING: The Cardiac Care Network, a registry of all
      patients having elective angiography at 18 hospitals in Ontario, Canada, between
      1 October 2008 and 30 September 2011. PATIENTS: Persons without prior coronary
      revascularization or myocardial infarction who had angiography for suspected
      stable CAD. MEASUREMENTS: Appropriateness scores were ascertained by using data
      collected at the time of the index angiography and were categorized as
      appropriate, inappropriate, or uncertain. RESULTS: Among the final cohort of 48
      336 patients, 58.2% of angiographic studies were classified as appropriate, 10.8%
      were classified as inappropriate, and 31.0% were classified as uncertain.
      Overall, 45.5% of patients had obstructive CAD. In patients with appropriate
      indications for angiography, 52.9% had obstructive CAD, with 40.0% undergoing
      revascularization. In those with inappropriate indications, 30.9% had obstructive
      CAD and 18.9% underwent revascularization; in those with uncertain indications,
      36.7% had obstructive CAD and 25.9% had revascularization. Although more patients
      with appropriate indications had obstructive CAD and underwent revascularization
      (P < 0.001), a substantial proportion of those with inappropriate or uncertain
      indications had important coronary disease. LIMITATION: Data were not available
      on whether symptoms were atypical. CONCLUSION: Despite the association between
      appropriateness category and obstructive CAD, this study raises concerns about
      the ability of the appropriate use criteria to guide clinical decision making.
      PRIMARY FUNDING SOURCE: Canadian Institutes of Health Research.

PMID- 25751587
TI  - Stick Together: A Nordic Walking Group Intervention for Breast Cancer Survivors.
AB  - Axillary lymph node dissection and axillary radiation as part of breast cancer
      treatment often result in arm and shoulder morbidity and limitations in daily
      functioning. Over and above the general benefits for cardiorespiratory fitness,
      Nordic Walking particularly targets at the muscles of the upper extremities and
      shoulder. This may increase shoulder range of motion and lead to a reduction in
      functional limitations. The aim of this study was to offer a Nordic Walking
      intervention to women after treatment for breast cancer and to investigate
      changes in subjective well-being and shoulder function. Three supervised Nordic
      Walking courses were organized (2009-2011). The intervention consisted of ten
      weekly 1-hour sessions focusing on upper body strength and condition. In total,
      28 women participated in one of the cohorts. Results showed that after 10 weeks,
      patients' vitality had improved, whereas perceived shoulder symptom severity and
      limitations in daily activities had decreased. Goniometric data indicated that
      range of motion (forward flexion, abduction, and external rotation) of the
      affected shoulder improved significantly within 10 weeks of training. Group
      interviews at 6 months follow-up confirmed that patients had appreciated the
      physical and psychosocial benefits of the intervention. These benefits outweighed
      the practical disadvantages. Patient selection, assessment and training should
      take place under (para-)medical supervision and group instructors should have the
      knowledge and skills to work with a group of recent cancer survivors. Results
      from this explorative study suggest that Nordic Walking is a feasible and
      potentially valuable tool in the rehabilitation of patients with breast cancer. 

PMID- 25751588
TI  - Using microwave heating to improve the desorption efficiency of high molecular
      weight VOC from beaded activated carbon.
AB  - Incomplete regeneration of activated carbon loaded with organic compounds results
      in heel build-up that reduces the useful life of the adsorbent. In this study,
      microwave heating was tested as a regeneration method for beaded activated carbon
      (BAC) loaded with n-dodecane, a high molecular weight volatile organic compound.
      Energy consumption and desorption efficiency for microwave-heating regeneration
      were compared with conductive-heating regeneration. The minimum energy needed to
      completely regenerate the adsorbent (100% desorption efficiency) using microwave
      regeneration was 6% of that needed with conductive heating regeneration, owing to
      more rapid heating rates and lower heat loss. Analyses of adsorbent pore size
      distribution and surface chemistry confirmed that neither heating method altered
      the physical/chemical properties of the BAC. Additionally, gas chromatography
      (with flame ionization detector) confirmed that neither regeneration method
      detectably altered the adsorbate composition during desorption. By demonstrating
      improvements in energy consumption and desorption efficiency and showing stable
      adsorbate and adsorbent properties, this paper suggests that microwave heating is
      an attractive method for activated carbon regeneration particularly when high
      affinity VOC adsorbates are present. 

PMID- 25751583
TI  - An Update of the Review of Neuropsychological Consequences of HIV and Substance
      Abuse: A Literature Review and Implications for Treatment and Future Research.
AB  - Neuropyschological dysfunction, ranging from mild cerebral indicators to dementia
      has been a consistent part of the medical picture of HIV/AIDS. However, advances
      in medical supervision, particularly as a result of antiretroviral (ARV)
      treatment, have resulted in some mitigation of the neuropsychological effects of
      HIV and necessitate re-evaluation of the pattern and nature of HIV-related
      cognitive or mental deficits. The associated enhancements in morbidity and
      mortality that have occurred as a result of ARV medication have led to a need for
      interventions and programs that maintain behaviors that are healthy and stop the
      resurgence of the risk of HIV transmission. Risk factors such as mental illness
      and substance use that may have contributed to the initial infection with HIV
      still need consideration. These risk factors may also increase neuropsychological
      dysfunction and impact observance of prevention for treatment and
      recommendations. Explicitly, a better comprehension of the role of substance use
      on the progression of HIV-related mental decline can enlighten management and
      evaluation of persons living with HIV with concurrent disorders of substance use.
      This review provides a summary of the neurophyschology of substance use and HIV
      and the existing research that has looked at the effects of both substance use
      and HIV disease on neurophyscological function and suggestions for future
      research and treatment. 

PMID- 25751589
TI  - Rotational stiffness of American football shoes affects ankle biomechanics and
      injury severity.
AB  - While previous studies have investigated the effect of shoe-surface interaction
      on injury risk, few studies have examined the effect of rotational stiffness of
      the shoe. The hypothesis of the current study was that ankles externally rotated
      to failure in shoes with low rotational stiffness would allow more talus eversion
      than those in shoes with a higher rotational stiffness, resulting in less severe
      injury. Twelve (six pairs) cadaver lower extremities were externally rotated to
      gross failure while positioned in 20 deg of pre-eversion and 20 deg of
      predorsiflexion by fixing the distal end of the foot, axially loading the
      proximal tibia, and internally rotating the tibia. One ankle in each pair was
      constrained by an American football shoe with a stiff upper, while the other was
      constrained by an American football shoe with a flexible upper. Experimental bone
      motions were input into specimen-specific computational models to examine levels
      of ligament elongation to help understand mechanisms of ankle joint failure.
      Ankles in flexible shoes allowed 6.7+/-2.4 deg of talus eversion during rotation,
      significantly greater than the 1.7+/-1.0 deg for ankles in stiff shoes (p =
      0.01). The significantly greater eversion in flexible shoes was potentially due
      to a more natural response of the ankle during rotation, possibly affecting the
      injuries that were produced. All ankles failed by either medial ankle injury or
      syndesmotic injury, or a combination of both. Complex (more than one ligament or
      bone) injuries were noted in 4 of 6 ankles in stiff shoes and 1 of 6 ankles in
      flexible shoes. Ligament elongations from the computational model validated the
      experimental injury data. The current study suggested flexibility (or rotational
      stiffness) of the shoe may play an important role in both the severity of ankle
      injuries for athletes. 

PMID- 25751591
TI  - Correction to "Enantioconvergent synthesis of functionalized gamma-butyrolactones
      via (3 + 2)-annulation".

PMID- 25751590
TI  - Novel Karyotypes and Cyclin D1 Immunoreactivity in Clear Cell Sarcoma of the
      Kidney.
AB  - Pathological diagnosis of clear cell sarcoma of the kidney (CCSK) is challenging
      as it resembles blastemal Wilms tumor (WT) and other pediatric sarcomas, and does
      not have any distinctive immunophenotype. The YWHAE-FAM22 translocation
      t(10;17)(q22;p13) has been reported in a subset of CCSK. This translocation also
      occurs in high-grade endometrial sarcoma, in which it is associated with cyclin
      D1 overexpression. Hence we seek to determine YWHAE-FAM22 translocation status
      and cyclin D1 immunoreactivity in a series of local CCSK cases. Of 8 CCSK cases
      from 7 patients identified, no CCSK had the YWHAE-FAM22 fusion transcript by
      reverse transcriptase-polymerase chain reaction. Novel karyotypes were identified
      for 2 cases: 1 had t(2;13)(q13;q22) and the other t(3:17)(q29;p11.2). Excluding a
      case with poor tissue section antigenicity, 7 of 7 CCSKs (100%) showed diffuse
      and strong nuclear cyclin D1 staining. Cyclin D1 immunohistochemistry was also
      performed on tissue microarrays of other pediatric renal tumors: blastemal areas
      of 18 WT cases were negative; 6 rhabdoid tumors and 1 metanephric adenoma showed
      patchy and weak staining; 3 mesoblastic nephromas and 18 of 29 neuroblastomas had
      positive staining. Cyclin D1 immunohistochemistry helps distinguish CCSK from
      blastemal WT and metanephric adenoma and rhabdoid tumors, but not from
      neuroblastomas and mesoblastic nephromas. Cyclin D1 overexpression in CCSK is not
      contingent on YWHAE-FAM22 translocation, and cyclin D1 inhibition may potentially
      be explored as a targeted therapeutic strategy in CCSK. 

PMID- 25751592
TI  - Detection of EGFR-TK domain-activating mutations in NSCLC with generic PCR-based
      methods.
AB  - Somatic mutations in the epidermal growth factor receptor-tyrosine kinase (EGFR
      TK) domain of non-small cell lung cancer (NSCLC) influence the responsiveness of
      these tumors to EGFR-TK inhibitors, indicating their usefulness as a predictive
      molecular marker. However, for mutation analysis, the amount of clinical material
      available from NSCLC patients is often very limited, suboptimally preserved, and
      composed of both normal and tumor cells. As a consequence, the total amount of
      recovered DNA is frequently very limited, with mutant alleles being often
      strongly underrepresented, and thus requiring highly sensitive methods for the
      detection of mutations. In the present study, EGFR mutation screening was
      performed on 210 NSCLC clinical samples by heminested polymerase chain reaction
      (PCR), followed by denaturing gradient gel electrophoresis (DGGE). Candidate
      mutations were further characterized by sequencing. Seventeen different types of
      pathogenic EGFR-TK domain mutations were detected in 55 of the 210 samples (26%).
      We reanalyzed 149 of the 155 samples in which no mutation was found by real-time
      PCR for the presence of recurrent exon 21 and exon 19 mutations using peptide
      nucleic acid probes in the PCR mix to increase sensitivity by mutant allele
      enrichment. Four additional samples with exon 19 mutations were detected. Thus,
      it is found that the relatively simple and inexpensive PCR-DGGE assay is already
      very sensitive for the detection of mutations in clinical samples, including
      samples with low tumor cellularity (10% or higher tumor cell content), although
      the sensitivity and speed of the assay can be further increased for a restricted
      panel of mutations by introducing peptide nucleic acid probes in the DGGE or real
      time PCR-based assay. 

PMID- 25751593
TI  - Fluorination, and tunneling across molecular junctions.
AB  - This paper describes the influence of the substitution of fluorine for hydrogen
      on the rate of charge transport by hole tunneling through junctions of the form
      Ag(TS)O2C(CH2)n(CF2)(m)T//Ga2O3/EGaIn, where T is methyl (CH3) or trifluoromethyl
      (CF3). Alkanoate-based self-assembled monolayers (SAMs) having perfluorinated
      groups (R(F)) show current densities that are lower (by factors of 20-30) than
      those of the homologous hydrocarbons (R(H)), while the attenuation factors of the
      simplified Simmons equation for methylene (beta = (1.05 +/- 0.02)n(CH2)(-1)) and
      difluoromethylene (beta = (1.15 +/- 0.02)n(CF2)(-1)) are similar (although the
      value for (CF2)n is statistically significantly larger). A comparative study
      focusing on the terminal fluorine substituents in SAMs of omega-tolyl- and 
      phenyl-alkanoates suggests that the C-F//Ga2O3 interface is responsible for the
      lower tunneling currents for CF3. The decrease in the rate of charge transport in
      SAMs with R(F) groups (relative to homologous R(H) groups) is plausibly due to an
      increase in the height of the tunneling barrier at the T//Ga2O3 interface, and/or
      to weak van der Waals interactions at that interface.

PMID- 25751594
TI  - Control of the metal-insulator transition in VO2 epitaxial film by modifying
      carrier density.
AB  - External controlling the phase transition behavior of vanadium dioxide is
      important to realize its practical applications as energy-efficient electronic
      devices. Because of its relatively high phase transition temperature of 68 
      degrees C, the central challenge for VO2-based electronics, lies in finding an
      energy efficient way, to modulate the phase transition in a reversible and
      reproducible manner. In this work, we report an experimental realization of p-n
      heterojunctions by growing VO2 film on p-type GaN substrate. By adding the bias
      voltage on the p-n junction, the metal-insulator transition behavior of VO2 film
      can be changed continuously. It is demonstrated that the phase transition of VO2
      film is closely associated with the carrier distribution within the space charge
      region, which can be directly controlled by the bias voltage. Our findings offer
      novel opportunities for modulating the phase transition of VO2 film in a
      reversible way as well as extending the concept of electric-field modulation on
      other phase transition materials. 

PMID- 25751595
TI  - Multisite analysis of the timing and outcomes of unplanned transfers from
      subacute to acute care.
AB  - OBJECTIVE: The aim of the present study was to examine the timing and outcomes of
      patients requiring an unplanned transfer from subacute to acute care. METHODS:
      Subacute care in-patients requiring unplanned transfer to an acute care facility
      within four Victorian health services from 1 January to 31 December 2010 were
      included in the study. Data were collected using retrospective audit. The primary
      outcome was transfer within 24 h of subacute care admission. RESULTS: In all, 431
      patients (median age 81 years) had unplanned transfers; of these, 37.8% had a
      limitation of medical treatment (LOMT) order. The median subacute care length of
      stay was 43 h: 29.0% of patients were transferred within 24 h and 83.5% were
      transferred within 72 h of subacute care admission. Predictors of transfer within
      24 h were comorbidity weighting (odds ratio (OR) 1.1, P = 0.02) and LOMT order
      (OR 2.1, P < 0.01). Hospital admission occurred in 87.2% of patients and 15.4%
      died in hospital. Predictors of in-hospital mortality were comorbidity weighting
      (OR 1.2, P < 0.01) and the number of physiological abnormalities in the 24 h
      preceding transfer (OR 1.3, P < 0.01). CONCLUSIONS: There is a high rate of
      unplanned transfers to acute care within 24h of admission to subacute care.
      Unplanned transfers are associated with high hospital admission and in-hospital
      mortality rates.

PMID- 25751596
TI  - Volatile Organic Compounds Off-gassing from Firefighters' Personal Protective
      Equipment Ensembles after Use.
AB  - Firefighters' personal protective equipment (PPE) ensembles will become
      contaminated with various compounds during firefighting. Some of these compounds
      will off-gas following a response, which could result in inhalation exposure.
      This study was conducted to determine the magnitude and composition of volatile
      organic compounds (VOCs) generated during controlled structure burns that
      subsequently off-gassed from the firefighters' PPE, and were systemically
      absorbed and exhaled in firefighters' breath. Three crews of five firefighters
      performed entry, suppression, and overhaul during a controlled burn. We used
      evacuated canisters to sample air inside the burn structure during active fire
      and overhaul. After each burn, we placed PPE from two firefighters inside clean
      enclosures and sampled the air using evacuated canisters over 15 min.
      Firefighters' exhaled breath was collected ~1 hr before and 4-14 min after each
      burn. Using gas chromatography/mass spectrometry, the evacuated canister samples
      were analyzed for 64 VOCs and the exhaled breath samples were analyzed for
      benzene, toluene, ethylbenzene, xylene, and styrene (BTEXS). Fourteen of the same
      VOCs were detected off-gassing from PPE in 50% or more of the samples. Compared
      to background levels, we measured >5 fold increases in mean off-gas
      concentrations of styrene, benzene, 1,4-dichlorobenzene, acetone, and
      cyclohexane. Several of the compounds detected off-gassing from PPE were also
      measured at concentrations above background during active fire and overhaul,
      including benzene, propene, and styrene. The overhaul and off-gas air
      concentrations were well below applicable short-term occupational exposure
      limits. Compared to pre-burn levels, we measured >2 fold increases in mean breath
      concentrations of benzene, toluene, and styrene after the burns. Air
      concentrations of BTEXS measured off-gassing from firefighters' used PPE and in
      firefighters' post-burn exhaled breath were significantly correlated. The
      firefighters may have absorbed BTEXS through both the dermal route (during
      firefighting) and inhalation route (from off-gassing PPE after firefighting).
      Firefighters should be made aware of the potential for inhalation exposure when
      doffing and traveling in confined vehicles with contaminated PPE and take
      measures to minimize this exposure pathway.

PMID- 25751597
TI  - Partial filling affinity capillary electrophoresis including adsorption energy
      distribution calculations--towards reliable and feasible biomolecular interaction
      studies.
AB  - In this work, a method to study and analyze the interaction data in free solution
      by exploiting partial filling affinity capillary electrophoresis (PF-ACE)
      followed by adsorption energy distribution calculations (AED) prior model fit to
      adsorption isotherms will be demonstrated. PF-ACE-AED approach allowed the
      possibility to distinguish weak and strong interactions of the binding processes
      between the most common apolipoprotein E protein isoforms (apoE2, apoE3, apoE4)
      of high density lipoprotein (HDL) and apoE-containing HDL2 with major
      glycosaminoglycan (GAG) chain of proteoglycans (PGs), chondroitin-6-sulfate
      (C6S). The AED analysis clearly revealed the heterogeneity of the binding
      processes. The major difference was that they were heterogeneous with two
      different adsorption sites for apoE2 and apoE4 isoforms, whereas interestingly
      for apoE3 and apoE-containing HDL2, the binding was homogeneous (one site)
      adsorption process. Moreover, our results allowed the evaluation of differences
      in the binding process strengths giving the following order with C6S: apoE
      containing HDL2 > apoE2 > apoE4 > apoE3. In addition, the affinity constant
      values determined could be compared with those obtained in our previous studies
      for the interactions between apoE isoforms and another important GAG chain of PGs
      - dermatan sulfate (DS). The success of the combination of AED calculations prior
      to non-linear adsorption isotherm model fit with PF-ACE when the concentration
      range was extended, confirmed the power of the system in the clarification of the
      heterogeneity of biological processes studied. 

PMID- 25751598
TI  - Mechanisms of starch digestion by alpha-amylase-Structural basis for kinetic
      properties.
AB  - Recent studies of the mechanisms determining the rate and extent of starch
      digestion by alpha-amylase are reviewed in the light of current widely-used
      classifications for (a) the proportions of rapidly-digestible (RDS), slowly
      digestible (SDS), and resistant starch (RS) based on in vitro digestibility, and
      (b) the types of resistant starch (RS 1,2,3,4...) based on physical and/or
      chemical form. Based on methodological advances and new mechanistic insights, it
      is proposed that both classification systems should be modified. Kinetic analysis
      of digestion profiles provides a robust set of parameters that should replace the
      classification of starch as a combination of RDS, SDS, and RS from a single
      enzyme digestion experiment. This should involve determination of the minimum
      number of kinetic processes needed to describe the full digestion profile,
      together with the proportion of starch involved in each process, and the kinetic
      properties of each process. The current classification of resistant starch types
      as RS1,2,3,4 should be replaced by one which recognizes the essential kinetic
      nature of RS (enzyme digestion rate vs. small intestinal passage rate), and that
      there are two fundamental origins for resistance based on (i) rate-determining
      access/binding of enzyme to substrate and (ii) rate-determining conversion of
      substrate to product once bound.

PMID- 25751599
TI  - Predictors of aided speech recognition, with and without frequency compression,
      in older adults.
AB  - OBJECTIVE: The aim was to investigate whether cognitive and/or audiological
      measures predict aided speech recognition, both with and without frequency
      compression (FC). DESIGN: Participants wore hearing aids, with and without FC for
      a total of 12 weeks (six weeks in each signal processing condition, ABA design).
      Performance on a sentence-in-noise recognition test was assessed at the end of
      each six-week period. Audiological (severity of high frequency hearing loss,
      presence of dead regions) and cognitive (reading span and trail making test
      scores) measures were obtained and assessed as predictors of sentence-in-noise
      recognition with and without FC enabled. STUDY SAMPLE: Twelve experienced hearing
      aid users (aged 65-84 years old) with moderate-to-severe high-frequency hearing
      loss took part in the study. RESULTS: The results suggest that both auditory and
      cognitive factors can be predictive of sentence-in-noise recognition with
      conventional amplification. However, only auditory factors were significantly
      correlated with the degree of benefit obtained from FC. CONCLUSIONS: The
      strongest predictor of aided speech recognition, both with and without FC, was
      high frequency hearing loss. Cognitive performance was also a predictor of
      benefit from conventional amplification, but not of additional benefit from the
      use of FC.

PMID- 25751602
TI  - Materialism Moderates the Effect of Accounting for Time on Prosocial Behaviors.
AB  - Accounting for time is defined as putting a price on time. Researchers have
      demonstrated that accounting for time reduces the time individuals spend on
      others; however, its association with monetary donations has not been examined.
      We hypothesized that accounting for time will activate a utility mindset that
      would affect one's allocation of time and money. In Study 1, the mediating effect
      of utility mindsets on the relationship between accounting for time and prosocial
      behavior was examined. In Study 2, we examined the effect of accounting for time
      on time spent helping and donating money, and the moderating role of material
      values on the relationship between accounting for time and prosocial behavior.
      Results showed that accounting for time activated a mindset of utility
      maximization that, in turn, reduced participants' prosocial behavior; moreover,
      materialism moderated the effect of accounting for time on prosocial behavior.

PMID- 25751601
TI  - The HMGB1-RAGE Inflammatory Pathway: Implications for Brain Injury-Induced
      Pulmonary Dysfunction.
AB  - SIGNIFICANCE: Deceased patients who have suffered severe traumatic brain injury
      (TBI) are the largest source of organs for lung transplantation. However, due to
      severely compromised pulmonary lung function, only one-third of these patients
      are eligible organ donors, with far fewer capable of donating lungs (~ 20%). As a
      result of this organ scarcity, understanding and controlling the pulmonary
      pathophysiology of potential donors are key to improving the health and long-term
      success of transplanted lungs. RECENT ADVANCES: Although the exact mechanism by
      which TBI produces pulmonary pathophysiology remains unclear, it may be related
      to the release of damage-associated molecular patterns (DAMPs) from the injured
      tissue. These heterogeneous, endogenous host molecules can be rapidly released
      from damaged or dying cells and mediate sterile inflammation following trauma. In
      this review, we highlight the interaction of the DAMP, high-mobility group box
      protein 1 (HMGB1) with the receptor for advanced glycation end-products (RAGE),
      and toll-like receptor 4 (TLR4). CRITICAL ISSUES: Recently published studies are
      reviewed, implicating the release of HMGB1 as producing marked changes in
      pulmonary inflammation and physiology following trauma, followed by an overview
      of the experimental evidence demonstrating the benefits of blocking the HMGB1
      RAGE axis. FUTURE DIRECTIONS: Targeting the HMGB1 signaling axis may increase the
      number of lungs available for transplantation and improve long-term benefits for
      organ recipient patient outcomes.

PMID- 25751603
TI  - Genomic analysis of ADAR1 binding and its involvement in multiple RNA processing
      pathways.
AB  - Adenosine deaminases acting on RNA (ADARs) are the primary factors underlying
      adenosine to inosine (A-to-I) editing in metazoans. Here we report the first
      global study of ADAR1-RNA interaction in human cells using CLIP-seq. A large
      number of CLIP sites are observed in Alu repeats, consistent with ADAR1's
      function in RNA editing. Surprisingly, thousands of other CLIP sites are located
      in non-Alu regions, revealing functional and biophysical targets of ADAR1 in the
      regulation of alternative 3' UTR usage and miRNA biogenesis. We observe that
      binding of ADAR1 to 3' UTRs precludes binding by other factors, causing 3' UTR
      lengthening. Similarly, ADAR1 interacts with DROSHA and DGCR8 in the nucleus and
      possibly out-competes DGCR8 in primary miRNA binding, which enhances mature miRNA
      expression. These functions are dependent on ADAR1's editing activity, at least
      for a subset of targets. Our study unfolds a broad landscape of the functional
      roles of ADAR1. 

PMID- 25751604
TI  - Shared decision making and use of decision AIDS for localized prostate cancer :
      perceptions from radiation oncologists and urologists.
AB  - IMPORTANCE: The current attitudes of prostate cancer specialists toward decision
      aids and their use in clinical practice to facilitate shared decision making are
      poorly understood. OBJECTIVE: To assess attitudes toward decision aids and their
      dissemination in clinical practice. DESIGN, SETTING, AND PARTICIPANTS: A survey
      was mailed to a national random sample of 1422 specialists (711 radiation
      oncologists and 711 urologists) in the United States from November 1, 2011,
      through April 30, 2012. MAIN OUTCOMES AND MEASURES: Respondents were asked about
      familiarity, perceptions, and use of decision aids for clinically localized
      prostate cancer and trust in various professional societies in developing
      decision aids. The Pearson chi2 test was used to test for bivariate associations
      between physician characteristics and outcomes. RESULTS: Similar response rates
      were observed for radiation oncologists and urologists (44.0% vs 46.1%; P=.46).
      Although most respondents had some familiarity with decision aids, only 35.5%
      currently use a decision aid in clinic practice. The most commonly cited barriers
      to decision aid use included the perception that their ability to estimate the
      risk of recurrence was superior to that of decision aids (7.7% in those not using
      decision aids and 26.2% in those using decision aids; P<.001) and the concern
      that patients could not process information from a decision aid (7.6% in those
      not using decision aids and 23.7% in those using decision aids; P<.001). In
      assessing trust in decision aids established by various professional medical
      societies, specialists consistently reported trust in favor of their respective
      organizations, with 9.2% being very confident and 59.2% being moderately
      confident (P=.01). CONCLUSIONS AND RELEVANCE: Use of decision aids among
      specialists treating patients with prostate cancer is relatively low. Efforts to
      address barriers to clinical implementation of decision aids may facilitate
      greater shared decision making for patients diagnosed as having prostate cancer.

PMID- 25751605
TI  - The Chinese-Western Intercultural Couple Standards Scale.
AB  - We developed the Chinese-Western Intercultural Couple Standards Scale (CWICSS) to
      assess relationship standards that may differ between Chinese and Western
      partners and may challenge intercultural couples. The scale assesses 4 Western
      derived relationship standards (demonstrations of love, demonstrations of caring,
      intimacy expression, and intimacy responsiveness) and 4 Chinese-derived
      relationship standards (relations with the extended family, relational harmony,
      face, and gender roles). We administered the CWICSS to 983 Chinese and Western
      participants living in Australia to assess the psychometric properties of the
      scores as measures of respondents' relationship standards. The CWICSS has a 2
      level factor structure with the items reflecting the 8 predicted standards. The 4
      Western derived standards loaded onto a higher order factor of couple bond, and
      the 4 Chinese derived standards loaded onto a higher order factor of family
      responsibility. The scale scores were structurally equivalent across cultures,
      genders, and 2 independent samples, and good convergent and discriminant validity
      was found for the interpretation of scale scores as respondents' endorsement of
      the predicted standards. Scores on the 8 scales and 2 superordinate scales showed
      high internal consistency and test-retest coefficients. Chinese endorsed all 4
      family responsibility standards more strongly than did Westerners, but Chinese
      and Western participants were similar in endorsement of couple bond standards.
      Across both cultures, couple bond standards were endorsed more highly than were
      family responsibility standards. The CWICSS assesses potential areas of conflict
      in Chinese-Western relationships.

PMID- 25751606
TI  - Multilevel multitrait-multimethod latent analysis of structurally different and
      interchangeable raters of school climate.
AB  - Informant-based systems of assessment are common platforms for measuring a
      variety of educational and psychological constructs where the use of multiple
      informants is considered best practice. In many instances, structurally different
      informant types (e.g., students and teachers) are solicited on the basis of their
      unique roles with the target of measurement. The use of multiple informants
      provides an opportunity to evaluate the degree to which the obtained ratings are
      influenced by the trait of focus and extraneous sources that can be attributed to
      the rater. Data from a multilevel multitrait-multimethod design in which students
      (N = 35,565) and teachers (N = 9,112), from 340 middle schools, responded to
      items measuring 3 dimensions of school climate were evaluated through a
      multilevel correlated trait-correlated method latent variable model. Results
      indicated that ratings of school climate obtained by students and teachers
      demonstrated high levels of convergent validity, and that school-level ratings
      obtained by students and teachers were equitable in the assessment of teasing and
      bullying. Student ratings of support and structure yielded somewhat stronger
      evidence of convergent validity than ratings obtained by teachers as revealed by
      their respective trait factor loadings. This was explained in part by the higher
      levels of common method effects that were observed for teachers.

PMID- 25751607
TI  - Forgotten Swallowed Wooden Toothpick Detected on Ultrasound.

PMID- 25751608
TI  - Acceptability of live attenuated influenza vaccine by vaccine providers in
      Quebec, Canada.
AB  - A live attenuated influenza vaccine (LAIV) was offered during the 2012-13
      influenza season in Quebec, Canada, to children aged between 2 and 17 years with
      chronic medical conditions. Despite the offer, uptake of the vaccine was low. We
      assessed the perceptions and opinions about seasonal influenza vaccination and
      LAIV use among vaccine providers who participated in the 2012-13 campaign. More
      than 70% of them thought that LAIV was safe and effective and more than 90%
      considered that the vaccine was well-received by parents and healthcare
      professionals. According to respondents, the most frequent concerns of parents
      about LAIV were linked to vaccine efficacy. LAIV is well-accepted by vaccine
      providers involved in influenza vaccination clinics, but more information about
      the vaccine and the recommendations for its use are needed to increase vaccine
      uptake.

PMID- 25751609
TI  - Stressful events during pregnancy and postpartum depressive symptoms.
AB  - BACKGROUND: Understanding the influence of perinatal stressors on the prevalence
      of postpartum depressive symptoms (PDS) and help-seeking for PDS using
      surveillance data can inform service provision and improve health outcomes.
      METHODS: We used Massachusetts Pregnancy Risk Assessment Monitoring System (MA
      PRAMS) 2007-2010 data to evaluate associations between selected perinatal
      stressors and PDS and with subsequent help-seeking behaviors. We categorized 12
      stressors into 4 groups: partner, traumatic, financial, and emotional. We defined
      PDS as reporting "always" or "often" to any depressive symptoms on PRAMS Phase 5,
      or to a composite score >=10 on PRAMS Phase 6 depression questions, compared with
      women reporting "sometimes," "rarely" or "never" to all depressive symptoms. The
      median response time to MA-PRAMS survey was 3.2 months (interquartile range, 2.9
      4.0 months). We estimated prevalence ratios (PRs) and 95% confidence intervals
      (95% CIs) using modified Poisson regression models, controlling for socioeconomic
      status indicators, pregnancy intention and prior mental health visits. RESULTS:
      Among 5,395 participants, 58% reported >=1 stressor (partner=26%, traumatic=16%,
      financial=29% and emotional=30%). Reporting of >=1 stressor was associated with
      increased prevalence of PDS (PR=1.68, 95% CI: 1.42-1.98). The strongest
      association was observed for partner stress (PR=1.90, 95% CI: 1.51-2.38). Thirty
      eight percent of mothers with PDS sought help. Mothers with partner-related
      stressors were less likely to seek help, compared with mothers with other grouped
      stressors. CONCLUSIONS: Women who reported perinatal common stressors
      particularly partner-related stressors-had an increased prevalence of PDS. These
      data suggest that women should be routinely screened during pregnancy for a range
      of stressors and encouraged to seek help for PDS.

PMID- 25751610
TI  - C-H Bond Cleavage by Bioinspired Nonheme Oxoiron(IV) Complexes, Including
      Hydroxylation of n-Butane.
AB  - The development of efficient and selective hydrocarbon oxidation processes with
      low environmental impact remains a major challenge of the 21st century because of
      the strong and apolar nature of the C-H bond. Naturally occurring iron-containing
      metalloenzymes can, however, selectively functionalize strong C-H bonds on
      substrates under mild and environmentally benign conditions. The key oxidant in a
      number of these transformations is postulated to possess an S = 2 Fe(IV)?O unit
      in a nonheme ligand environment. This oxidant has been trapped and
      spectroscopically characterized and its reactivity toward C-H bonds demonstrated
      for several nonheme iron enzyme classes. In order to obtain insight into the
      structure-activity relationships of these reactive intermediates, over 60
      synthetic nonheme Fe(IV)(O) complexes have been prepared in various laboratories
      and their reactivities investigated. This Forum Article summarizes the current
      status of efforts in the characterization of the C-H bond cleavage reactivity of
      synthetic Fe(IV)(O) complexes and provides a snapshot of the current
      understanding of factors that control this reactivity, such as the properties of
      the supporting ligands and the spin state of the iron center. In addition, new
      results on the oxidation of strong C-H bonds such as those of cyclohexane and n
      butane by a putative S = 2 synthetic Fe(IV)(O) species that is generated in situ
      using dioxygen at ambient conditions are presented. 

PMID- 25751611
TI  - Widening rural-urban disparities in youth suicides, United States, 1996-2010.
AB  - IMPORTANCE: Little is known about recent trends in rural-urban disparities in
      youth suicide, particularly sex- and method-specific changes. Documenting the
      extent of these disparities is critical for the development of policies and
      programs aimed at eliminating geographic disparities. OBJECTIVE: To examine
      trends in US suicide mortality for adolescents and young adults across the rural
      urban continuum. DESIGN, SETTING, AND PARTICIPANTS: Longitudinal trends in
      suicide rates by rural and urban areas between January 1, 1996, and December 31,
      2010, were analyzed using county-level national mortality data linked to a rural
      urban continuum measure that classified all 3141 counties in the United States
      into distinct groups based on population size and adjacency to metropolitan
      areas. The population included all suicide decedents aged 10 to 24 years. MAIN
      OUTCOMES AND MEASURES: Rates of suicide per 100,000 persons. RESULTS: Across the
      study period, 66,595 youths died by suicide, and rural suicide rates were nearly
      double those of urban areas for both males (19.93 and 10.31 per 100,000,
      respectively) and females (4.40 and 2.39 per 100,000, respectively). Even after
      controlling for a wide array of county-level variables, rural-urban suicide
      differentials increased over time for males, suggesting widening rural-urban
      disparities (1996-1998: adjusted incidence rate ratio [IRR], 0.98; 2008-2010:
      adjusted IRR, 1.19; difference in IRR, P = .02). Firearm suicide rates declined,
      and the rates of hanging/suffocation for both males and females increased.
      However, the rates of suicide by firearm (males: 1996-1998, 2.05; and 2008-2010:
      2.69 times higher) and hanging/suffocation (males: 1996-1998, 1.24; and 2008
      2010: 1.63 times higher) were disproportionately higher in rural areas, and rural
      urban differences increased over time (P = .002 for males; P = .06 for females).
      CONCLUSIONS AND RELEVANCE: Suicide rates for adolescents and young adults are
      higher in rural than in urban communities regardless of the method used, and
      rural-urban disparities appear to be increasing over time. Further research
      should carefully explore the mechanisms whereby rural residence might increase
      suicide risk in youth and consider suicide-prevention efforts specific to rural
      settings.

PMID- 25751613
TI  - Proteolysis process in fermented sausage model systems as studied by NMR
      relaxometry.
AB  - Proton NMR relaxation analyses were performed in sausage model systems (SMS) at
      different manufacturing times (0, 1, 3, 5, 7, and 9 days) to evaluate changes in
      water distribution and mobility. Three different water populations were
      identified, T2b (5-10 ms), T21 (30-70 ms), and T22 (100-300 ms), and the progress
      of ripening could be followed as a shift toward shorter relaxation times. In
      addition, the combined effect of adding commercial proteases (Pronase E and
      aspartyl proteinase) on protein breakdown and structural integrity of sausage
      models (SMS+P) was investigated, resulting in the formation of a more fluid and
      less organized meat matrix that led to changes in water populations T2b2 and T22
      compared with SMS. A very different protein degradation pattern between SMS and
      SMS+P was observed by means of SDS-PAGE and fluorescamine assay, supporting that
      some degree of protein aggregation is needed for the presence of the T22
      population in fermented sausages. 

PMID- 25751612
TI  - Peer Victimization and Harsh Parenting Predict Cognitive Diatheses for Depression
      in Children and Adolescents.
AB  - The current study examined peer victimization and harsh parenting as longitudinal
      predictors of broadband and narrowband cognitions associated with the etiology of
      depression in children and adolescents. The sample consisted of 214 elementary
      and middle school students. At the start of the study, their average age was 12.2
      years (SD = 1.0). The sex ratio was 112 girls to 102 boys. The sample was
      ethnically diverse (58.9% Caucasian, 34.1% African American, 10.7% Hispanic, 3.3%
      Asian, and 5.2% other). Children and their parents completed measures of peer
      victimization and harsh parenting. At two waves 1 year apart, children also
      completed questionnaire measures of negative and positive broadband cognitive
      style (e.g., personal failure, global self-worth) and narrowband self-perceptions
      (e.g., perceived social threat, social acceptance). Every Wave 2 cognitive
      variable was predicted by peer victimization or harsh parenting or both, even
      after controlling for a Wave 1 measure of the same cognitive variable. Peer
      victimization more consistently predicted narrowband social/interpersonal
      cognitions, whereas harsh parenting more consistently predicted broadband
      positive and negative cognitions. Furthermore, controlling for positive and
      negative self-cognitions eliminated a statistically significant effect of harsh
      parenting and peer victimization on depressive symptoms. Support emerged for the
      social learning of negative self-cognitions. Support also emerged for negative
      self-cognitions as a mediator of depressive symptoms. Implications for theory and
      practice are discussed.

PMID- 25751614
TI  - Using ultrasound visual biofeedback to treat persistent primary speech sound
      disorders.
AB  - Growing evidence suggests that speech intervention using visual biofeedback may
      benefit people for whom visual skills are stronger than auditory skills (for
      example, the hearing-impaired population), especially when the target
      articulation is hard to describe or see. Diagnostic ultrasound can be used to
      image the tongue and has recently become more compact and affordable leading to
      renewed interest in it as a practical, non-invasive visual biofeedback tool. In
      this study, we evaluate its effectiveness in treating children with persistent
      speech sound disorders that have been unresponsive to traditional therapy
      approaches. A case series of seven different children (aged 6-11) with persistent
      speech sound disorders were evaluated. For each child, high-speed ultrasound (121
      fps), audio and lip video recordings were made while probing each child's
      specific errors at five different time points (before, during and after
      intervention). After intervention, all the children made significant progress on
      targeted segments, evidenced by both perceptual measures and changes in tongue
      shape. 

PMID- 25751615
TI  - Near-infrared fluorescent probe for imaging mitochondrial hydrogen polysulfides
      in living cells and in vivo.
AB  - Hydrogen polysulfides (H2Sn, n > 1), derived from hydrogen sulfide (H2S), have
      attracted increasing attention in biochemical research, which may perform as the
      actual signaling molecules during cell signaling processes. Because of the closed
      biological and chemical relationship between H2S and H2Sn, it is of great value
      to develop sensitive and specific techniques to distinguish the intracellular
      level of H2Sn. To improve the understanding of the physiological and pathological
      roles played by H2Sn, we now develop a specific fluorescent probe Mito-ss for
      capturing H2Sn in cells and in vivo. When triggered by H2Sn, Mito-ss replies a
      turn-on fluorescence signal and exhibits a higher selectivity toward H2Sn than
      other abundant competing biothiols, such as glutathione, cysteine and H2S. The
      probe Mito-ss can also be applied to visual H2Sn in living cells, as well as in
      vivo, providing a potentially powerful approach for probing H2Sn in biological
      systems. 

PMID- 25751616
TI  - Reaction mechanism of cobalt-substituted homoprotocatechuate 2,3-dioxygenase: a
      QM/MM study.
AB  - The reaction mechanisms of cobalt-substituted homoprotocatechuate 2,3-dioxygenase
      (Co-HPCD) with electron-rich substrate homoprotocatechuate (HPCA) and electron
      poor substrate 4-nitrocatechol (4NC) were investigated by quantum
      mechanical/molecular mechanical (QM/MM) calculations. Our results demonstrated
      that the Co-O2 adducts has doublet ground state with a Co(III)-O2(*-) character
      when 4NC was used as the substrate, in good agreement with the EPR spectroscopic
      experiment. The reactive oxygen species is the doublet Co(III)-O2(*-) for Co
      HPCD/4NC and the quartet SQ(*?)-Co(II)-O2(*-?) species for Co-HPCD/HPCA,
      indicating that the substrate plays important roles in the dioxygen activation by
      Co-HPCD. B3LYP was found to overestimate the rate-limiting barriers in Co-HPCD.
      TPSSh predicts barriers of 21.5 versus 12.0 kcal/mol for Co-HPCD/4NC versus Co
      HPCD/HPCA, which is consistent with the fact that the rate of the reaction is
      decreased when the substrate was changed from HPCA to 4NC. 

PMID- 25751617
TI  - Mobile Laboratory Observations of Methane Emissions in the Barnett Shale Region.
AB  - Results of mobile ground-based atmospheric measurements conducted during the
      Barnett Shale Coordinated Campaign in spring and fall of 2013 are presented.
      Methane and ethane are continuously measured downwind of facilities such as
      natural gas processing plants, compressor stations, and production well pads.
      Gaussian dispersion simulations of these methane plumes, using an iterative
      forward plume dispersion algorithm, are used to estimate both the source location
      and the emission magnitude. The distribution of emitters is peaked in the 0-5
      kg/h range, with a significant tail. The ethane/methane molar enhancement ratio
      for this same distribution is investigated, showing a peak at ~1.5% and a broad
      distribution between ~4% and ~17%. The regional distributions of source emissions
      and ethane/methane enhancement ratios are examined: the largest methane emissions
      appear between Fort Worth and Dallas, while the highest ethane/methane
      enhancement ratios occur for plumes observed in the northwestern potion of the
      region. Individual facilities, focusing on large emitters, are further analyzed
      by constraining the source location. 

PMID- 25751618
TI  - Left atrial appendage morphology in patients with suspected cardiogenic stroke
      without known atrial fibrillation.
AB  - The left atrial appendage (LAA) is the typical origin for intracardiac thrombus
      formation. Whether LAA morphology is associated with increased stroke/TIA risk is
      controversial and, if it does, which morphological type most predisposes to
      thrombus formation. We assessed LAA morphology in stroke patients with
      cryptogenic or suspected cardiogenic etiology and in age- and gender-matched
      healthy controls. LAA morphology and volume were analyzed by cardiac computed
      tomography in 111 patients (74 males; mean age 60 +/- 11 years) with acute
      ischemic stroke of cryptogenic or suspected cardiogenic etiology other than known
      atrial fibrillation (AF). A subgroup of 40 patients was compared to an age- and
      gender-matched control group of 40 healthy individuals (21 males in each; mean
      age 54 +/- 9 years). LAA was classified into four morphology types (Cactus,
      ChickenWing, WindSock, CauliFlower) modified with a quantitative qualifier. The
      proportions of LAA morphology types in the main stroke group, matched stroke
      subgroup, and control group were as follows: Cactus (9.0%, 5.0%, 20.0%),
      ChickenWing (23.4%, 37.5%, 10.0%), WindSock (47.7%, 35.0%, 67.5%), and
      CauliFlower (19.8%, 22.5%, 2.5%). The distribution of morphology types differed
      significantly (P<0.001) between the matched stroke subgroup and control group.
      The proportion of single-lobed LAA was significantly higher (P<0.001) in the
      matched stroke subgroup (55%) than the control group (6%). LAA volumes were
      significantly larger (P<0.001) in both stroke study groups compared to controls
      patients. To conclude, LAA morphology differed significantly between stroke
      patients and controls, and single-lobed LAAs were overrepresented and LAA volume
      was larger in patients with acute ischemic stroke of cryptogenic or suspected
      cardiogenic etiology. 

PMID- 25751619
TI  - Seeking sex online: social and sexual risk factors among adolescent and young gay
      and bisexual men.
AB  - Background With the increased use of the Internet to seek sex, research has
      documented its associated sexual risk behaviours, especially among gay and
      bisexual men. Only a few studies to date have been conducted among adolescent and
      young men, and these have focussed on behavioural components to do with seeking
      sex online, without considering the role of same-sex identity formation
      processes. The current study aimed to identify behavioural and identity formation
      variables associated with seeking sex online among adolescents and youth.
      METHODS: A web sampling of young Israeli gay and bisexual men aged 12-30 years
      (n=445) was used to assess their seeking sex online characteristics, mental
      health, sexual risk behaviours, substance use, same-sex disclosure and acceptance
      and coping resources. RESULTS: Nearly half of the sample used the Internet to
      seek sex, which was correlated with substance use and sexual risk behaviour.
      Young adults seek for sex online more commonly than adolescents. Higher numbers
      of: sexual partners, level of outness, levels of friends support and stronger
      connectedness to the gay community predicted seeking sex online. Seeking sex
      online was found to be more of predictor for sexual risk behaviour than any other
      predictor. CONCLUSIONS: Seeking sex online is influenced by the gay sub-culture
      climate and peer group relationships, rather than by social stressor variables
      related to sexual orientation formation processes, or by the subject's general
      mental health condition. These results underscore the possible risks pertaining
      to seeking sex among gay and bisexual men and the possible use for this venue to
      convey safe-sex messages to adolescents and young adults.

PMID- 25751621
TI  - Emerging risk factors as markers for carotid intima media thickness scores.
AB  - AIMS: Cardiovascular disease (CVD) remains the number one cause of mortality in
      the Western world. This study aims to determine which lifestyle factors are
      associated with mean carotid intima media thickness (IMT), a safe and reliable
      predictor of future CVD risk. METHODS AND RESULTS: A prospective cross-sectional
      analysis of 592 subjects. Measures were made of body composition, anthropometric
      measures, fitness, diet (measured with a 3-day food diary), laboratory results,
      and mean carotid IMT. Multivariate analyses show that higher mean IMT values are
      associated with increasing age (p < 0.0001), male gender (p = 0.0002), higher
      systolic blood pressure (BP; p = 0.0008), higher body mass index (BMI; p =
      0.0005), and lower intake of zinc (p = 0.0001). Bivariate analyses controlling
      for age and gender, with and without statin use, showed that higher mean IMT
      scores were statistically associated with higher diastolic BP (p = 0.007), higher
      total cholesterol/high-density lipoprotein (HDL) ratio (p < 0.0001), higher
      triglyceride/HDL ratio (p = 0.0001), lower aerobic capacity measures (p =
      0.0007), higher body fat percentage and waist circumference (p < 0.0001), higher
      fasting glucose level (p = 0.028), and lower intake of magnesium (p = 0.019),
      fish (p = 0.007), and fiber (p = 0.02). Other factors that were not associated
      with mean IMT include total cholesterol, low-density lipoprotein cholesterol (LDL
      C), and high-sensitivity C-reactive protein (hs-CRP); intake of saturated fat,
      potassium, calcium, sodium, or vitamin K; percentage of calories from protein,
      fat, or carbohydrate; measures of strength (assessed with push-up and sit-up
      testing); and reported exercise. CONCLUSIONS: Aerobic fitness and dietary intake
      of fiber, fish, magnesium, and zinc are inversely associated with carotid IMT
      scores. Of the traditional CVD risk factors, only systolic BP, fasting glucose,
      body composition, and total cholesterol/HDL ratio have a direct relationship with
      mean carotid IMT.

PMID- 25751620
TI  - Efficient differentiation of steroidogenic and germ-like cells from
      epigenetically-related iPSCs derived from ovarian granulosa cells.
AB  - To explore restoration of ovarian function using epigenetically-related, induced
      pluripotent stem cells (iPSCs), we functionally evaluated the epigenetic memory
      of novel iPSC lines, derived from mouse and human ovarian granulosa cells (GCs)
      using c-Myc, Klf4, Sox2 and Oct4 retroviral vectors. The stem cell identity of
      the mouse and human GC-derived iPSCs (mGriPSCs, hGriPSCs) was verified by
      demonstrating embryonic stem cell (ESC) antigen expression using
      immunocytochemistry and RT-PCR analysis, as well as formation of embryoid bodies
      (EBs) and teratomas that are capable of differentiating into cells from all three
      germ layers. GriPSCs' gene expression profiles associate more closely with those
      of ESCs than of the originating GCs as demonstrated by genome-wide analysis of
      mRNA and microRNA. A comparative analysis of EBs generated from three different
      mouse cell lines (mGriPSCs; fibroblast-derived iPSC, mFiPSCs; G4 embryonic stem
      cells, G4 mESCs) revealed that differentiated mGriPSC-EBs synthesize 10-fold more
      estradiol (E2) than either differentiated FiPSC- or mESC-EBs under identical
      culture conditions. By contrast, mESC-EBs primarily synthesize progesterone (P4)
      and FiPSC-EBs produce neither E2 nor P4. Differentiated mGriPSC-EBs also express
      ovarian markers (AMHR, FSHR, Cyp19a1, ER and Inha) as well as markers of early
      gametogenesis (Mvh, Dazl, Gdf9, Boule and Zp1) more frequently than EBs of the
      other cell lines. These results provide evidence of preferential homotypic
      differentiation of mGriPSCs into ovarian cell types. Collectively, our data
      support the hypothesis that generating iPSCs from the desired tissue type may
      prove advantageous due to the iPSCs' epigenetic memory. 

PMID- 25751622
TI  - HIF-1alpha activation by intermittent hypoxia requires NADPH oxidase stimulation
      by xanthine oxidase.
AB  - Hypoxia-inducible factor 1 (HIF-1) mediates many of the systemic and cellular
      responses to intermittent hypoxia (IH), which is an experimental model that
      simulates O2 saturation profiles occurring with recurrent apnea. IH-evoked HIF
      1alpha synthesis and stability are due to increased reactive oxygen species (ROS)
      generated by NADPH oxidases, especially Nox2. However, the mechanisms by which IH
      activates Nox2 are not known. We recently reported that IH activates xanthine
      oxidase (XO) and the resulting increase in ROS elevates intracellular calcium
      levels. Since Nox2 activation requires increased intracellular calcium levels, we
      hypothesized XO-mediated calcium signaling contributes to Nox activation by IH.
      We tested this possibility in rat pheochromocytoma PC12 cells subjected to IH
      consisting alternating cycles of hypoxia (1.5% O2 for 30 sec) and normoxia (21%
      O2 for 5 min). Kinetic analysis revealed that IH-induced XO preceded Nox
      activation. Inhibition of XO activity either by allopurinol or by siRNA prevented
      IH-induced Nox activation, translocation of the cytosolic subunits p47phox and
      p67phox to the plasma membrane and their interaction with gp91phox. ROS generated
      by XO also contribute to IH-evoked Nox activation via calcium-dependent protein
      kinase C stimulation. More importantly, silencing XO blocked IH-induced
      upregulation of HIF-1alpha demonstrating that HIF-1alpha activation by IH
      requires Nox2 activation by XO. 

PMID- 25751623
TI  - Self-assembled peptide amphiphile nanofibers and peg composite hydrogels as
      tunable ECM mimetic microenvironment.
AB  - Natural extracellular matrix (ECM) consists of complex signals interacting with
      each other to organize cellular behavior and responses. This sophisticated
      microenvironment can be mimicked by advanced materials presenting essential
      biochemical and physical properties in a synergistic manner. In this work, we
      developed a facile fabrication method for a novel nanofibrous self-assembled
      peptide amphiphile (PA) and poly(ethylene glycol) (PEG) composite hydrogel system
      with independently tunable biochemical, mechanical, and physical cues without any
      chemical modification of polymer backbone or additional polymer processing
      techniques to create synthetic ECM analogues. This approach allows noninteracting
      modification of multiple niche properties (e.g., bioactive ligands, stiffness,
      porosity), since no covalent conjugation method was used to modify PEG monomers
      for incorporation of bioactivity and porosity. Combining the self-assembled PA
      nanofibers with a chemically cross-linked polymer network simply by facile mixing
      followed by photopolymerization resulted in the formation of porous bioactive
      hydrogel systems. The resulting porous network can be functionalized with desired
      bioactive signaling epitopes by simply altering the amino acid sequence of the
      self-assembling PA molecule. In addition, the mechanical properties of the
      composite system can be precisely controlled by changing the PEG concentration.
      Therefore, nanofibrous self-assembled PA/PEG composite hydrogels reported in this
      work can provide new opportunities as versatile synthetic mimics of ECM with
      independently tunable biological and mechanical properties for tissue engineering
      and regenerative medicine applications. In addition, such systems could provide
      useful tools for investigation of how complex niche cues influence cellular
      behavior and tissue formation both in two-dimensional and three-dimensional
      platforms. 

PMID- 25751628
TI  - Extraversion and psychopathology: A facet-level analysis.
AB  - The goal of this study was to explicate how the lower order facets of
      extraversion are related to psychopathology. We used a "bottom-up" approach in
      which specific extraversion scales from 3 comprehensive personality inventories
      were used to model these facets as latent factors. We collected both self-report
      and interview measures of a broad range of psychopathology from a large community
      sample. Replicating previous findings using a similar approach (Naragon-Gainey &
      Watson, 2014; Naragon-Gainey, Watson, & Markon, 2009), structural analyses
      yielded four factors: Positive Emotionality, Sociability, Assertiveness, and
      Experience Seeking. Scores on these latent dimensions were related to
      psychopathology in correlational analyses and in two sets of regressions (the
      first series used the four facets as predictors; the second included composite
      scores on the other Big Five domains as additional predictors). These results
      revealed a striking level of specificity. As predicted, Positive Emotionality
      displayed especially strong negative links to depressive symptoms and diagnoses.
      Sociability also was negatively related to psychopathology, showing particularly
      strong associations with indicators of social dysfunction and the negative
      symptoms of schizotypy (i.e., social anxiety, social aloofness, and restricted
      affectivity). Assertiveness generally had weak associations at the bivariate
      level but was negatively related to social anxiety and was positively correlated
      with some forms of externalizing. Finally, Experience Seeking had substantial
      positive associations with a broad range of indicators related to externalizing
      and bipolar disorder; it also displayed negative links to agoraphobia. These
      differential correlates demonstrate the importance of examining personality
      psychopathology relations at the specific facet level.

PMID- 25751629
TI  - Better informing decision making with multiple outcomes cost-effectiveness
      analysis under uncertainty in cost-disutility space.
AB  - INTRODUCTION: Comparing multiple, diverse outcomes with cost-effectiveness
      analysis (CEA) is important, yet challenging in areas like palliative care where
      domains are unamenable to integration with survival. Generic multi-attribute
      utility values exclude important domains and non-health outcomes, while partial
      analyses-where outcomes are considered separately, with their joint relationship
      under uncertainty ignored-lead to incorrect inference regarding preferred
      strategies. OBJECTIVE: The objective of this paper is to consider whether such
      decision making can be better informed with alternative presentation and summary
      measures, extending methods previously shown to have advantages in multiple
      strategy comparison. METHODS: Multiple outcomes CEA of a home-based palliative
      care model (PEACH) relative to usual care is undertaken in cost disutility (CDU)
      space and compared with analysis on the cost-effectiveness plane. Summary
      measures developed for comparing strategies across potential threshold values for
      multiple outcomes include: expected net loss (ENL) planes quantifying differences
      in expected net benefit; the ENL contour identifying preferred strategies
      minimising ENL and their expected value of perfect information; and cost
      effectiveness acceptability planes showing probability of strategies minimising
      ENL. RESULTS: Conventional analysis suggests PEACH is cost-effective when the
      threshold value per additional day at home (??1) exceeds $1,068 or dominated by
      usual care when only the proportion of home deaths is considered. In contrast,
      neither alternative dominate in CDU space where cost and outcomes are jointly
      considered, with the optimal strategy depending on threshold values. For example,
      PEACH minimises ENL when ??1=$2,000 and ??2=$2,000 (threshold value for dying at
      home), with a 51.6% chance of PEACH being cost-effective. CONCLUSION: Comparison
      in CDU space and associated summary measures have distinct advantages to multiple
      domain comparisons, aiding transparent and robust joint comparison of costs and
      multiple effects under uncertainty across potential threshold values for effect,
      better informing net benefit assessment and related reimbursement and research
      decisions.

PMID- 25751627
TI  - De novo loss- or gain-of-function mutations in KCNA2 cause epileptic
      encephalopathy.
AB  - Epileptic encephalopathies are a phenotypically and genetically heterogeneous
      group of severe epilepsies accompanied by intellectual disability and other
      neurodevelopmental features. Using next-generation sequencing, we identified four
      different de novo mutations in KCNA2, encoding the potassium channel KV1.2, in
      six isolated patients with epileptic encephalopathy (one mutation recurred three
      times independently). Four individuals presented with febrile and multiple
      afebrile, often focal seizure types, multifocal epileptiform discharges strongly
      activated by sleep, mild to moderate intellectual disability, delayed speech
      development and sometimes ataxia. Functional studies of the two mutations
      associated with this phenotype showed almost complete loss of function with a
      dominant-negative effect. Two further individuals presented with a different and
      more severe epileptic encephalopathy phenotype. They carried mutations inducing a
      drastic gain-of-function effect leading to permanently open channels. These
      results establish KCNA2 as a new gene involved in human neurodevelopmental
      disorders through two different mechanisms, predicting either hyperexcitability
      or electrical silencing of KV1.2-expressing neurons. 

PMID- 25751631
TI  - Pentoxifylline for treatment of sepsis and necrotizing enterocolitis in neonates.
AB  - BACKGROUND: Mortality and morbidity due to neonatal sepsis and necrotizing
      enterocolitis (NEC) remain high despite the use of potent antimicrobial agents.
      Agents that modulate inflammation may improve outcomes. Pentoxifylline, a
      phosphodiesterase inhibitor, is one such agent. OBJECTIVES: Our primary
      objectives were :1.To assess the effect of intravenous pentoxifylline as an
      adjunct to antibiotic therapy on mortality and morbidity in neonates with
      suspected or confirmed sepsis.2.To assess the effect of intravenous
      pentoxifylline as an adjunct to antibiotic therapy on mortality and morbidity in
      neonates with NEC. SEARCH METHODS: We searched the Cochrane Neonatal Review Group
      Specialized Register, CENTRAL (The Cochrane Library Issue 2, 2014), EMBASE
      (January 1980 to May 2014), PubMed (January 1966 to May 2014), CINAHL (January
      1982 to May 2014), Science Citation Index (January 1990 to May 2014), and BIOSIS
      (January 1992 May 2014) in May 2014. We checked references and cross-references
      from identified studies. We handsearched abstracts from the proceedings of the
      Pediatric Academic Societies Meetings (from January 1990 to May 2014). We placed
      no restrictions on language. SELECTION CRITERIA: We included randomised or quasi
      randomised trials assessing the efficacy of pentoxifylline as an adjunct to
      antibiotics for treatment of suspected or confirmed sepsis or NEC in neonates.
      DATA COLLECTION AND ANALYSIS: We reported typical risk ratio (RR) and risk
      difference (RD) with 95% confidence intervals (CI) using fixed-effect model for
      dichotomous outcomes and mean difference (MD) for continuous outcomes. We
      calculated the number needed to treat for an additional beneficial outcome (NNTB)
      if there was a statistically significant reduction in RD. MAIN RESULTS:
      Pentoxifylline used as an adjunct to antibiotics in neonates with sepsis
      decreased all-cause mortality during hospital stay (typical RR 0.57, 95% CI 0.35
      to 0.93; typical RD -0.08, 95% CI -0.14 to -0.01; NNTB 13, 95% CI 7 to 100; 6
      studies, 416 participants, low-quality evidence). Subgroup analyses revealed
      decrease in mortality in preterm infants, infants with confirmed sepsis, and
      infants with gram-negative sepsis (low-quality evidence, four studies).
      Pentoxifylline decreased length of hospital stay (MD -7.59 days, 95% CI -11.65 to
      -3.52; 2 studies, 148 participants, low-quality evidence). Pentoxifylline did not
      change the risk of development of NEC, chronic lung disease, severe
      intraventricular haemorrhage, retinopathy of prematurity, or periventricular
      leukomalacia in neonates with sepsis (one to two studies, very low-quality
      evidence). Pentoxifylline therapy compared to pentoxifylline and immunoglobulin M
      enriched intravenous immunoglobulin or immunoglobulin M-enriched intravenous
      immunoglobulin alone did not change mortality or development of NEC in neonates
      with sepsis (one study, very low-quality evidence). We noted no adverse effects
      due to pentoxifylline. We identified no trials evaluating pentoxifylline
      treatment for NEC. AUTHORS' CONCLUSIONS: Low-quality evidence from six small
      studies suggests that pentoxifylline therapy as an adjunct to antibiotics in
      neonatal sepsis decreases mortality without any adverse effects. We encourage
      researchers to undertake large, well-designed multicentre trials to confirm or
      refute the effectiveness of pentoxifylline in reducing mortality and morbidity in
      neonates with sepsis or NEC.

PMID- 25751626
TI  - A genetic mechanism for female-limited Batesian mimicry in Papilio butterfly.
AB  - In Batesian mimicry, animals avoid predation by resembling distasteful models. In
      the swallowtail butterfly Papilio polytes, only mimetic-form females resemble the
      unpalatable butterfly Pachliopta aristolochiae. A recent report showed that a
      single gene, doublesex (dsx), controls this mimicry; however, the detailed
      molecular mechanisms remain unclear. Here we determined two whole-genome
      sequences of P. polytes and a related species, Papilio xuthus, identifying a
      single ~130-kb autosomal inversion, including dsx, between mimetic (H-type) and
      non-mimetic (h-type) chromosomes in P. polytes. This inversion is associated with
      the mimicry-related locus H, as identified by linkage mapping. Knockdown
      experiments demonstrated that female-specific dsx isoforms expressed from the
      inverted H allele (dsx(H)) induce mimetic coloration patterns and simultaneously
      repress non-mimetic patterns. In contrast, dsx(h) does not alter mimetic
      patterns. We propose that dsx(H) switches the coloration of predetermined wing
      patterns and that female-limited polymorphism is tightly maintained by
      chromosomal inversion. 

PMID- 25751632
TI  - Immunostimulant properties of chemical delivery systems in vaccine development.
AB  - One approach to improve the vaccine quality is the incorporation of
      immunomodulators and/or adjuvants with modified delivery systems. The use of
      delivery systems especially chemical carriers is a promising strategy in the
      prevention and treatment of infections, cancers, allergies and autoimmune
      diseases. These systems are able to elicit an effective immune response as well
      as stability and safety in vaccine development. Synthetic microparticles,
      liposomes, chitosan, virus like particle, polymeric nanogel, phytosome, noisome,
      and micro/ nanospheres have been applied as carriers, providing a broad variety
      of immunomodulatory effects in vaccines. The potency and nature of immune
      responses rely on the physicochemical properties of the vaccine constructs (e.g.,
      size and charge), the route of injection, the biochemical characteristics and the
      amount of antigen. Three main steps are necessary for vaccine efficiency such as
      targeting, activation and transfection/ antigen presentation. These systems can
      generally influence the type and direction of immune responses. This review
      describes different vaccine delivery systems developed to generate
      immunomodulatory effects. 

PMID- 25751624
TI  - Fine mapping of type 1 diabetes susceptibility loci and evidence for
      colocalization of causal variants with lymphoid gene enhancers.
AB  - Genetic studies of type 1 diabetes (T1D) have identified 50 susceptibility
      regions, finding major pathways contributing to risk, with some loci shared
      across immune disorders. To make genetic comparisons across autoimmune disorders
      as informative as possible, a dense genotyping array, the Immunochip, was
      developed, from which we identified four new T1D-associated regions (P < 5 * 10(
      8)). A comparative analysis with 15 immune diseases showed that T1D is more
      similar genetically to other autoantibody-positive diseases, significantly most
      similar to juvenile idiopathic arthritis and significantly least similar to
      ulcerative colitis, and provided support for three additional new T1D risk loci.
      Using a Bayesian approach, we defined credible sets for the T1D-associated SNPs.
      The associated SNPs localized to enhancer sequences active in thymus, T and B
      cells, and CD34(+) stem cells. Enhancer-promoter interactions can now be analyzed
      in these cell types to identify which particular genes and regulatory sequences
      are causal. 

PMID- 25751630
TI  - The Induction of Pattern-Recognition Receptor Expression against Influenza A
      Virus through Duox2-Derived Reactive Oxygen Species in Nasal Mucosa.
AB  - We studied the relative roles of Duox2-derived reactive oxygen species (ROS) in
      host defense against influenza A virus (IAV) infection in normal human nasal
      epithelial cells and mouse nasal mucosa. We found that Duox2 primarily generated
      ROS rapidly after IAV infection in normal human nasal epithelial cells and that
      knockdown of Duox2 aggravated IAV infection. In addition, Duox2-derived ROS
      enhancement significantly suppressed IAV infection in nasal epithelium. In
      particular, Duox2-derived ROS were required for the induction of retinoic acid
      inducible gene (RIG)-I and melanoma differentiation-associated protein 5 (MDA5)
      transcription. After intranasal IAV inoculation into mice, viral infection was
      significantly aggravated from 3 days postinoculation (dpi) in the nasal mucosa,
      and the IAV viral titer was highest at 7 dpi. Both RIG-I and MDA5 messenger RNA
      levels increased dominantly in mouse nasal mucosa from 3 dpi; consistent with
      this, RIG-I and MDA5 proteins were also induced after IAV infection. RIG-I and
      MDA5 messenger RNA levels were induced to a lower extent in the nasal mucosa of
      the mice that were inoculated with Duox2 short hairpin RNA, and the IAV viral
      titer was significantly higher in nasal lavage. Taken together, Duox2-derived ROS
      are necessary for the innate immune response and trigger the induction of RIG-I
      and MDA5 to resist IAV infection in human nasal epithelium and mouse nasal
      mucosa.

PMID- 25751633
TI  - Long-Term Outcomes of Primary Intraocular Lens Implantation for Unilateral
      Congenital Cataract.
AB  - PURPOSE: In congenital cataracts, the need for early intervention is well
      established to prevent visual deprivation and amblyopia. We evaluated patients
      with unilateral amblyogenic congenital who had undergone simultaneous cataract
      removal and intraocular lens implantation. METHODS: We retrospectively reviewed
      all patients operated on between 1990 and 2010 at the Pediatric Eye Department of
      the University Federico II of Naples (Italy). Minimum follow-up for inclusion was
      48 months. RESULTS: 52 patients (28 females, 24 males, mean age at surgery 9.0 +/
      4.5 months, range 2-21 months) were included in this retrospective review. Mean
      follow-up was 100.7 +/- 57.0 months (range, 48-270 months). At last visit, mean
      BCVA in the operated eyes was 0.65 +/- 0.4 (range, 0.04-1.3) LogMAR and 40
      patients (76.9%) had strabismus. In patients undergoing surgery at an age >12
      months, BCVA was significantly lower (0.92 +/- 0.4 LogMAR versus 0.60 +/- 0.4
      LogMAR, p = 0.01), although development of myopic shift was less frequent (61.5%
      versus 43.5%, p = 0.03). BCVA at last visit was higher in patients with a first
      stable pseudophakic SE between +1D and +3D (p = 0.02). CONCLUSIONS: Worse final
      BCVA, despite less frequent development of myopic shift, was observed when
      surgery was performed after 12 months of age. A hyperopic correction in first
      stable pseudophakic SE seems advisable.

PMID- 25751635
TI  - Quantitative sub-surface and non-contact imaging using scanning microwave
      microscopy.
AB  - The capability of scanning microwave microscopy for calibrated sub-surface and
      non-contact capacitance imaging of silicon (Si) samples is quantitatively studied
      at broadband frequencies ranging from 1 to 20 GHz. Calibrated capacitance images
      of flat Si test samples with varying dopant density (10(15)-10(19) atoms cm(-3))
      and covered with dielectric thin films of SiO2 (100-400 nm thickness) are
      measured to demonstrate the sensitivity of scanning microwave microscopy (SMM)
      for sub-surface imaging. Using standard SMM imaging conditions the dopant areas
      could still be sensed under a 400 nm thick oxide layer. Non-contact SMM imaging
      in lift-mode and constant height mode is quantitatively demonstrated on a 50 nm
      thick SiO2 test pad. The differences between non-contact and contact mode
      capacitances are studied with respect to the main parameters influencing the
      imaging contrast, namely the probe tip diameter and the tip-sample distance.
      Finite element modelling was used to further analyse the influence of the tip
      radius and the tip-sample distance on the SMM sensitivity. The understanding of
      how the two key parameters determine the SMM sensitivity and quantitative
      capacitances represents an important step towards its routine application for non
      contact and sub-surface imaging. 

PMID- 25751634
TI  - Enhanced High-Density Line Spectral-Domain Optical Coherence Tomography Imaging
      of the Vitreoretinal Interface: Description of Selected Cases.
AB  - PURPOSE: We introduce a new method to observe the morphologic features of the
      vitreous with spectral-domain optical coherence tomography (SD-OCT) by evaluating
      and describing the posterior vitreous structure of various selected cases using
      enhanced high-density (HD) line mode. METHODS: This is a descriptive case series
      of SD-OCT images with enhanced HD line at Denver Health Medical Center,
      University of Colorado School of Medicine, in 2014. The medical records with
      ocular images for these patients were analyzed. RESULTS: Enhanced HD line in
      vitreoretinal mode with SD-OCT offered wide images with well-visible
      vitreoretinal interface. The posterior precortical vitreous pocket (PPVP), often
      mistaken as a posterior vitreous detachment on standard retina-based cross line
      mode, was easily identified. Vitreomacular adhesion and traction, absence or
      presence of connecting channels between PPVP and Cloquet's canal, liquefied
      vitreous lacuna, and emulsified silicone oil droplet-layer could be observed.
      CONCLUSIONS: SD-OCT using enhanced HD line in vitreoretinal mode enables clear
      visualization of the posterior vitreous structure and often reclassifies patients
      previously thought to have a posterior vitreous detachment.

PMID- 25751636
TI  - The impact of in-season national team soccer play on injury and player
      availability in a professional club.
AB  - This study investigated the impact of in-season national team duty on injury
      rates and player availability in a professional soccer club. Time-loss injuries
      and exposure time during club and national team duties were recorded
      prospectively over 5 seasons (2009-2014). A time-loss injury was sustained by
      37.7% of squad members participating in national duty, all injuries occurring in
      match-play. The incidence (per 1000 h exposure) for national team player match
      play injuries did not differ (P = 0.608) to that for all players in club
      competitions: 48.0 (95% CI 20.9-75.5) vs. 41.9 (95% CI 36.5-47.4), incidence rate
      ratio = 1.2 (CI: 0.8-2.4). The majority (58%) of national team injuries resulted
      in a layoff <=1 week. Of all working days lost to injury generally, 5.2% were
      lost through injury on national duty. Injury incidence in the week following
      national duty was comparable (P = 0.818) in players participating or not: 7.8
      (95% CI 3.6-12.0) vs. 7.1 (95% CI: 4.6-9.6), incidence rate ratio = 1.1 (CI: 0.7
      2.7). While approximately 40% of participating players incurred a time-loss
      injury on national duty, no training injuries were sustained and injuries made up
      a negligible part of overall club working days lost to injury. Following duty,
      players had a similar injury risk to peers without national obligations. 

PMID- 25751625
TI  - Genome-wide association analysis of more than 120,000 individuals identifies 15
      new susceptibility loci for breast cancer.
AB  - Genome-wide association studies (GWAS) and large-scale replication studies have
      identified common variants in 79 loci associated with breast cancer, explaining
      ~14% of the familial risk of the disease. To identify new susceptibility loci, we
      performed a meta-analysis of 11 GWAS, comprising 15,748 breast cancer cases and
      18,084 controls together with 46,785 cases and 42,892 controls from 41 studies
      genotyped on a 211,155-marker custom array (iCOGS). Analyses were restricted to
      women of European ancestry. We generated genotypes for more than 11 million SNPs
      by imputation using the 1000 Genomes Project reference panel, and we identified
      15 new loci associated with breast cancer at P < 5 * 10(-8). Combining
      association analysis with ChIP-seq chromatin binding data in mammary cell lines
      and ChIA-PET chromatin interaction data from ENCODE, we identified likely target
      genes in two regions: SETBP1 at 18q12.3 and RNF115 and PDZK1 at 1q21.1. One
      association appears to be driven by an amino acid substitution encoded in EXO1. 

PMID- 25751637
TI  - Genome-Wide Analysis of ChREBP Binding Sites on Male Mouse Liver and White
      Adipose Chromatin.
AB  - Glucose is an essential nutrient that directly regulates the expression of
      numerous genes in liver and adipose tissue. The carbohydrate response element
      binding protein (ChREBP) links glucose as a signaling molecule to multiple
      glucose-dependent transcriptional regulatory pathways, particularly genes
      involved in glycolytic and lipogenic processes. In this study, we used chromatin
      immunoprecipitation followed by next-generation sequencing to identify specific
      ChREBP binding targets in liver and white adipose tissue. We found a large number
      of ChREBP binding sites, which are attributable to 5825 genes in the liver, 2418
      genes in white adipose tissue, and 5919 genes in both tissues. The majority of
      these target genes were involved in known metabolic processes. Pathways in
      insulin signaling, the adherens junction, and cancers were among the top 5
      pathways in both tissues. Motif analysis revealed a consensus sequence
      CAYGYGnnnnnCRCRTG that was commonly shared by ChREBP binding sites. Putative
      ChREBP binding sequences were enriched on promoters of genes involved in insulin
      signaling pathway, insulin resistance, and tumorigenesis. 

PMID- 25751638
TI  - Tachykinin-1 in the central nervous system regulates adiposity in rodents.
AB  - Ghrelin is a circulating hormone that targets the central nervous system to
      regulate feeding and adiposity. The best-characterized neural system that
      mediates the effects of ghrelin on energy balance involves the activation of
      neuropeptide Y/agouti-related peptide neurons, expressed exclusively in the
      arcuate nucleus of the hypothalamus. However, ghrelin receptors are expressed in
      other neuronal populations involved in the control of energy balance. We combined
      laser capture microdissection of several nuclei of the central nervous system
      expressing the ghrelin receptor (GH secretagoge receptor) with microarray gene
      expression analysis to identify additional neuronal systems involved in the
      control of central nervous system-ghrelin action. We identified tachykinin-1
      (Tac1) as a gene negatively regulated by ghrelin in the hypothalamus.
      Furthermore, we identified neuropeptide k as the TAC1-derived peptide with more
      prominent activity, inducing negative energy balance when delivered directly into
      the brain. Conversely, loss of Tac1 expression enhances the effectiveness of
      ghrelin promoting fat mass gain both in male and in female mice and increases the
      susceptibility to diet-induced obesity in ovariectomized mice. Taken together,
      our data demonstrate a role TAC1 in the control energy balance by regulating the
      levels of adiposity in response to ghrelin administration and to changes in the
      status of the gonadal function. 

PMID- 25751640
TI  - Correction to "Asymmetric synthesis of diverse glycolic acid scaffolds via
      dynamic kinetic resolution of alpha-keto esters".

PMID- 25751639
TI  - Muscle-specific deletion of comparative gene identification-58 (CGI-58) causes
      muscle steatosis but improves insulin sensitivity in male mice.
AB  - Intramyocellular accumulation of lipids is often associated with insulin
      resistance. Deficiency of comparative gene identification-58 (CGI-58) causes
      cytosolic deposition of triglyceride (TG)-rich lipid droplets in most cell types,
      including muscle due to defective TG hydrolysis. It was unclear, however, whether
      CGI-58 deficiency-induced lipid accumulation in muscle influences insulin
      sensitivity. Here we show that muscle-specific CGI-58 knockout mice relative to
      their controls have increased glucose tolerance and insulin sensitivity on a
      Western-type high-fat diet, despite TG accumulation in both heart and oxidative
      skeletal muscle and cholesterol deposition in heart. Although the
      intracardiomyocellular lipid deposition results in cardiac ventricular fibrosis
      and systolic dysfunction, muscle-specific CGI-58 knockout mice show increased
      glucose uptake in heart and soleus muscle, improved insulin signaling in insulin
      sensitive tissues, and reduced plasma concentrations of glucose, insulin, and
      cholesterol. Hepatic contents of TG and cholesterol are also decreased in these
      animals. Cardiac steatosis is attributable, at least in part, to decreases in
      cardiac TG hydrolase activity and peroxisome proliferator-activated receptor
      alpha/peroxisome proliferator-activated receptor-gamma coactivator-1-dependent
      mitochondrial fatty acid oxidation. In conclusion, muscle CGI-58 deficiency
      causes cardiac dysfunction and fat deposition in oxidative muscles but induces a
      series of favorable metabolic changes in mice fed a high-fat diet. 

PMID- 25751642
TI  - "But I wasn't told to": lack of education and workplace policy as barriers in the
      provision of family planning information.
AB  - Access to family planning has been identified as critical to public health.
      Improving the linkage between medical and social services could result in
      improved access to care for those most at risk of unintended pregnancy. This
      study used a survey based on Alfred Bandura's social cognitive theory (1986) to
      increase the understanding of the barriers social workers confront in the
      provision of family planning information to clients. Although moral disagreement
      with family planning presented a barrier for some, workplace policy,
      participation in family planning trainings, and working in an urban setting were
      of greater value in understanding barriers. 

PMID- 25751643
TI  - Dissociating H2+(2Sigmag+,JM=00) ion as an exploding quantum bubble.
AB  - The nuclear and electronic probability and flux densities for a vibrating and
      dissociating H2(+) molecular ion in the electronic and rotational ground state
      (corresponding to the quantum numbers 2Sigma(g)+,JM=00) are calculated. As a
      consequence of the isotropy of the scenario, the vibrating H2(+) appears as a
      pulsating quantum bubble, while the dissociating H2(+) appears as an exploding
      quantum bubble. The dissociating part is represented by a discretization of the
      continuum through use of L2 integrable B-spline basis set. It is shown that the
      vibrating part (the pulsating quantum bubble) interferes with the dissociating
      part (the exploding quantum bubble) and that the interference is much more
      noticeable in the probability density than in the flux density.

PMID- 25751641
TI  - Lessons learned from successful human vaccines: Delineating key epitopes by
      dissecting the capsid proteins.
AB  - Recombinant VLP-based vaccines have been successfully used against 3 diseases
      caused by viral infections: Hepatitis B, cervical cancer and hepatitis E. The VLP
      approach is attracting increasing attention in vaccine design and development for
      human and veterinary use. This review summarizes the clinically relevant epitopes
      on the VLP antigens in successful human vaccines. These virion-like epitopes,
      which can be delineated with molecular biology, cryo-electron microscopy and x
      ray crystallographic methods, are the prerequisites for these efficacious
      vaccines to elicit functional antibodies. The critical epitopes and key factors
      influencing these epitopes are discussed for the HEV, HPV and HBV vaccines. A
      pentamer (for HPV) or a dimer (for HEV and HBV), rather than a monomer, is the
      basic building block harboring critical epitopes for the assembly of VLP antigen.
      The processing and formulation of VLP-based vaccines need to be developed to
      promote the formation and stabilization of these epitopes in the recombinant
      antigens. Delineating the critical epitopes is essential for antigen design in
      the early phase of vaccine development and for critical quality attribute
      analysis in the commercial phase of vaccine manufacturing. 

PMID- 25751644
TI  - Second allo-SCT in patients with lymphoma relapse after a first allogeneic
      transplantation. A retrospective study of the EBMT Lymphoma Working Party.
AB  - The aim of this registry-based retrospective study was to analyze the outcome of
      second allogeneic hematopoietic SCT (alloHSCT_2) performed in patients with
      lymphoma who had relapsed after a first allogeneic transplant (alloHSCT_1).
      Patients ?18 years who had received an alloHSCT_2 for lymphoma relapse between
      2000 and 2011 were eligible. One hundred and forty patients were identified. The
      diagnosis was Hodgkin lymphoma (HL) in 31%, diffuse large B-cell lymphoma in 14%,
      T-cell lymphoma in 12%, indolent lymphoma in 19%, mantle cell lymphoma in 16% and
      other lymphomas in 8% of the patients. The median interval from alloHSCT_1 to
      alloHSCT_2 was 19 (range 4-116) months. Disease status at alloHSCT_2 was
      chemosensitive in 46%, refractory in 43% and unknown in 11% of the patients.
      Three-year PFS, OS, relapse incidence and nonrelapse mortality were 19%, 29%, 58%
      and 23%, respectively. PFS and OS were significantly affected by refractory
      disease at alloHSCT_2 and a short interval between alloHSCT_1 and alloHSCT_2.
      Long-term PFS was observed across all lymphoma subsets except for aggressive B
      cell lymphoma. In conclusion, alloHSCT_2 is feasible and can result in long-term
      disease control in patients with lymphoma recurrence after alloHSCT_1, in
      particular if relapse occurs late and is chemosensitive. 

PMID- 25751645
TI  - Serum free light chain trends between orthotopic heart transplantation and auto
      SCT in patients with AL amyloidosis.

PMID- 25751646
TI  - G-CSF plus preemptive plerixafor vs hyperfractionated CY plus G-CSF for
      autologous stem cell mobilization in multiple myeloma: effectiveness, safety and
      cost analysis.
AB  - The optimal stem cell mobilization regimen for patients with multiple myeloma
      (MM) remains undefined. We retrospectively compared our experience in
      hematopoietic cell mobilization in 83 MM patients using fractionated high-dose CY
      and G-CSF with G-CSF plus preemptive plerixafor. All patients in the CY group
      (n=56) received fractionated high-dose CY (5 g/m(2) divided into five doses of 1
      g/m(2) every 3 h) with G-CSF. All patients in the plerixafor group (n=27)
      received G-CSF and plerixafor preemptively based on an established algorithm.
      Compared with plerixafor, CY use was associated with higher total CD34+ cell
      yield (7.5 * 10(6) vs 15.5 * 10(6) cells/kg, P=0.005). All patients in both
      groups yielded ?4 * 10(6) CD34+ cells/kg. Conversely, CY use was associated with
      high frequency of febrile neutropenia, blood and platelet transfusions need and
      hospitalizations. The average total cost of mobilization in Lebanon was slightly
      higher in the plerixafor group ($7886 vs $7536; P=0.16). Our data indicate robust
      stem cell mobilization in MM patients with either fractionated high-dose CY and G
      CSF or G-CSF alone with preemptive plerixafor. The chemo-mobilization approach
      was associated with twofold stem cell yield, slightly lower cost but
      significantly increased toxicity. 

PMID- 25751647
TI  - Beyond consolidation: auto-SCT and immunotherapy for plasma cell myeloma.
AB  - Autologous hematopoietic cell transplantation (auto-HCT) is the standard
      consolidation therapy for plasma cell myeloma patients following induction
      therapy. Auto-HCT improves disease-free survival (DFS), but is generally not
      curative. The allogeneic HCT experience demonstrated that T-cell immunotherapy
      can confer long-term DFS. Preclinical and clinical data indicate that myeloma
      associated Ags elicit humoral and cellular immune responses (IRs) in myeloma
      patients. These findings strongly suggest that the immunotherapeutic strategies,
      including immune checkpoint inhibitors, therapeutic cancer vaccines and adoptive
      cellular therapies, are promising avenues of clinical research that may be most
      applicable in the minimal residual disease state following auto-HCT. These
      strategies are designed to prime or augment antimyeloma IRs and promote a 'host
      vs-myeloma' effect that may result in durable DFS. Innovative clinical trials
      investigating immune checkpoint inhibitors and cancer vaccines have demonstrated
      that robust immunity against myeloma-associated Ags can be elicited in the
      setting of auto-HCT. A diverse array of immunotherapeutic strategies have entered
      clinical trials in myeloma, including PD-1/PD-L1 inhibitors, DC/myeloma cell
      fusion vaccines and adoptive chimeric Ag receptor T-cell therapy, and further
      investigation of combinations of immunologic and pharmaceutical agents are
      expected in the near future. In this review, we will discuss the preclinical data
      supporting immunotherapy in auto-HCT for myeloma, clinical investigation of these
      strategies and the future prospects of immunotherapy in pursuit of the goal of
      curative therapy. 

PMID- 25751649
TI  - Reflections on supervision in psychotherapy.
AB  - The aim of the author is to share his reflections on supervision as a central
      topic in therapists' education and training programs. The concept of supervision,
      its functions and effects on the training process along with the contributions of
      different theoretical models to its evolution are addressed. Supervision
      alliance, the roles of supervisor and supervisee, evaluation as a central
      component and the influence of socioeconomic factors are discussed. The
      conclusions depict the most interesting paths for development in the near future
      and the areas where research needs to be further conducted along with the
      subjects most worthy of efforts in the supervision field. 

PMID- 25751648
TI  - Reading out a spatiotemporal population code by imaging neighbouring parallel
      fibre axons in vivo.
AB  - The spatiotemporal pattern of synaptic inputs to the dendritic tree is crucial
      for synaptic integration and plasticity. However, it is not known if input
      patterns driven by sensory stimuli are structured or random. Here we investigate
      the spatial patterning of synaptic inputs by directly monitoring presynaptic
      activity in the intact mouse brain on the micron scale. Using in vivo calcium
      imaging of multiple neighbouring cerebellar parallel fibre axons, we find
      evidence for clustered patterns of axonal activity during sensory processing. The
      clustered parallel fibre input we observe is ideally suited for driving dendritic
      spikes, postsynaptic calcium signalling, and synaptic plasticity in downstream
      Purkinje cells, and is thus likely to be a major feature of cerebellar function
      during sensory processing. 

PMID- 25751650
TI  - Effect of reactor configuration on performance during anaerobic treatment of low
      strength wastewater.
AB  - The efficiency of the up-flow anaerobic sludge blanket (UASB) reactor is quite
      low for the treatment of low strength wastewaters (LSWs) due to less biogas
      production leading to poor mixing. LSW may be treated efficiently by providing
      adequate mixing in the UASB reactor when gas production is low, and sufficient
      mixing can be achieved by modifying reactor geometry. Hence, modifying UASB
      reactor geometry for enhanced mixing and evaluating its performance for the
      treatment of LSWs would be a worthwhile effort. In the present study, UASB
      reactor configuration was modified by providing a vertical baffle along the
      height to promote mixing of reactor contents, and is termed as modified UASB
      (MUASB). The performance of an on-site pilot-scale MUASB reactor was evaluated
      for 375 days under ambient condition for the treatment of municipal sewage as LSW
      and compared with that of the conventional UASB and hybrid UASB (HUASB) reactors.
      The MUASB reactor showed better performance in terms of chemical oxygen demand
      (COD) removal efficiency as compared with UASB and HUASB reactors during this
      study. At 4 h hydraulic retention time, the total COD removal efficiency of UASB
      and HUASB reactors was 53.7% and 61%, respectively, which were much lower than
      the total COD removal efficiency of the MUASB reactor (72.7%). The better
      performance observed in the MUASB reactor is possibly due to improved mixing.
      Depth-wise analysis of reactor liquid showed that better mixing in the MUASB
      reactor enhances the contact of wastewater with biomass, which contributes to the
      improved treatment efficiency. It seems that MUASB holds promise for LSW
      treatment.

PMID- 25751651
TI  - PW1/Peg3 expression regulates key properties that determine mesoangioblast stem
      cell competence.
AB  - Mesoangioblasts are vessel-associated progenitor cells that show therapeutic
      promise for the treatment of muscular dystrophy. Mesoangioblasts have the ability
      to undergo skeletal muscle differentiation and cross the blood vessel wall
      regardless of the developmental stage at which they are isolated. Here we show
      that PW1/Peg3 is expressed at high levels in mesoangioblasts obtained from mouse,
      dog and human tissues and its level of expression correlates with their myogenic
      competence. Silencing PW1/Peg3 markedly inhibits myogenic potential of
      mesoangioblasts in vitro through MyoD degradation. Moreover, lack of PW1/Peg3
      abrogates mesoangioblast ability to cross the vessel wall and to engraft into
      damaged myofibres through the modulation of the junctional adhesion molecule-A.
      We conclude that PW1/Peg3 function is essential for conferring proper
      mesoangioblast competence and that the determination of PW1/Peg3 levels in human
      mesoangioblasts may serve as a biomarker to identify the best donor populations
      for therapeutic application in muscular dystrophies. 

PMID- 25751652
TI  - Apoplastic ROS production upon pollination by RbohH and RbohJ in Arabidopsis.
AB  - Reactive oxygen species (ROS) accumulate at the tip of growing pollen tubes. In
      Arabidopsis, NADPH oxidases RbohH and RbohJ are localized at the plasma membrane
      of pollen tube tip and produce ROS in a Ca(2+)-dependent manner. The ROS produced
      by Rbohs and Ca(2+) presumably play a critical role in the positive feedback
      regulation that maintains the tip growth. Ultrastructural cytochemical analysis
      revealed ROS accumulation in the apoplast/cell wall of the pollen grains on the
      stigmatic papillae in the wild type, but not in the rbohH rbohJ double mutant,
      suggesting that apoplastic ROS derived from RbohH and RbohJ are involved in
      pollen tube elongation into the stigmatic papillae by affecting the cell wall
      metabolism. 

PMID- 25751653
TI  - Ultrathin undoped tetrahedral amorphous carbon films: thickness dependence of the
      electronic structure and implications for their electrochemical behaviour.
AB  - In this paper we show that the electronic properties of ultrathin tetrahedral
      amorphous carbon (ta-C) films are heavily dependent on their thickness. By using
      scanning tunnelling spectroscopy, Raman spectroscopy, and conductive atomic force
      microscopy, it was found that a decrease of ta-C thickness from 30 to 7 nm leads
      to (i) the narrowing of the band gap; (ii) appearance of shallower monoenergetic
      traps as well as the increase of their concentration; (iii) the increase of the
      equilibrium concentration of free charge carriers and their mobility; which were
      caused by (iv) the increase in the sp(2) fraction. However, beyond a certain ta-C
      thickness (7 nm) the electronic properties of the studied samples start to
      deteriorate, which is highly likely related to titanium oxide formation at the
      Ti/ta-C interface. The same tendency is observed for the sample with beforehand
      air-formed native titanium oxide at the interface. With respect to the last
      point, it is suggested that the ta-C layer has no uniform coverage if its
      thickness is small enough (less than 7 nm). The experimental results were
      rationalized by detailed atomistic simulations. By using the so-called "Tauc
      plot" we introduce the possibility of the coexistence of bulk and surface band
      gaps originating from the large increase in sp(2) bonded carbon atoms in the
      surface region compared to that in the bulk ta-C. The results from the
      simulations were found to be consistent with the experimental measurements. The
      previously stated variation in the electronic properties of the layers as a
      function of their thickness was also exhibited in the electrochemical properties
      of the samples. It appears that the thinner ta-C layers had more facile electron
      transfer kinetics as determined with a ferrocenemethanol (FcMeOH) outer sphere
      redox system. However, if the ta-C layer thickness was reduced too much, the
      films were not stable anymore. 

PMID- 25751654
TI  - Methane baseline concentrations and sources in shallow aquifers from the shale
      gas-prone region of the St. Lawrence lowlands (Quebec, Canada).
AB  - Hydraulic fracturing is becoming an important technique worldwide to recover
      hydrocarbons from unconventional sources such as shale gas. In Quebec (Canada),
      the Utica Shale has been identified as having unconventional gas production
      potential. However, there has been a moratorium on shale gas exploration since
      2010. The work reported here was aimed at defining baseline concentrations of
      methane in shallow aquifers of the St. Lawrence Lowlands and its sources using
      delta(13)C methane signatures. Since this study was performed prior to large
      scale fracturing activities, it provides background data prior to the eventual
      exploitation of shale gas through hydraulic fracturing. Groundwater was sampled
      from private (n = 81), municipal (n = 34), and observation (n = 15) wells between
      August 2012 and May 2013. Methane was detected in 80% of the wells with an
      average concentration of 3.8 +/- 8.8 mg/L, and a range of <0.0006 to 45.9 mg/L.
      Methane concentrations were linked to groundwater chemistry and distance to the
      major faults in the studied area. The methane delta(1)(3)C signature of 19
      samples was > -500/00, indicating a potential thermogenic source. Localized areas
      of high methane concentrations from predominantly biogenic sources were found
      throughout the study area. In several samples, mixing, migration, and oxidation
      processes likely affected the chemical and isotopic composition of the gases,
      making it difficult to pinpoint their origin. Energy companies should respect a
      safe distance from major natural faults in the bedrock when planning the
      localization of hydraulic fracturation activities to minimize the risk of
      contaminating the surrounding groundwater since natural faults are likely to be a
      preferential migration pathway for methane. 

PMID- 25751656
TI  - Using a Paralleled Origin of Sampling Line to Prevent its Intraoperative Kinking.

PMID- 25751655
TI  - One-stage vs. two-stage brachio-basilic arteriovenous fistula for dialysis
      access: a systematic review and a meta-analysis.
AB  - INTRODUCTION: A brachiobasilic arteriovenous fistula (BB-AVF) can provide access
      for haemodialysis in patients who are not eligible for a more superficial
      fistula. However, it is unclear whether one- or two-stage BB-AVF is the best
      option for patients. AIM: To systematically assess the difference between both
      procedures in terms of access maturation, patency and postoperative
      complications. METHODS: Online search for randomised controlled trials (RCTs) and
      observational studies that compared the one-stage versus the two-stage technique
      for creating a BB-AVF. RESULTS: Eight studies were included (849 patients with
      859 fistulas), 366 created using a one-stage technique, while 493 in a two-stage
      approach. There was no statistically significant difference between the two
      groups in the rate of successful maturation (Pooled risk ratio = 0.95 [0.82,
      1.11], P = 0.53). Similarly, the incidence of postoperative haematoma (Pooled
      risk ratio = 0.73 [0.34, 1.58], P = 0.43), wound infection (Pooled risk ratio =
      0.77 [0.35, 1.68], P = 0.51) and steal syndrome (Pooled risk ratio = 0.65 [0.27,
      1.53], P = 0.32) were statistically comparable. CONCLUSION: Although more studies
      seem to favour the two-stage BVT approach, evidence in the literature is not
      sufficient to draw a final conclusion as the difference between the one-stage and
      the two-stage approaches for creation of a BB-AVF is not statistically
      significant in terms of the overall maturation rate and postoperative
      complications. Patency rates (primary, assisted primary and secondary) were
      comparable in the majority of studies. Large randomised properly conducted trials
      with superior methodology and adequate sub-group analysis are needed before
      making a final recommendation.

PMID- 25751657
TI  - Gas Sampling Line Versus Sampling Port.

PMID- 25751659
TI  - Formulation and Characterization of Aceclofenac -Aloe vera Transemulgel.
AB  - The present research was aimed to formulate aceclofenac transemulgel using Aloe
      vera as gel base. The prepared formulations were subjected to physical
      characterization, in-vitro and in-vivo assessment. Aceclofenac, a hydrophobic
      potential non steroidal anti inflammatory drug, causes ulceration upon chronic
      oral administration, could be formulated into transemulgel to enhance therapeutic
      efficacy and to lower the unwanted side effects. The transemulgel was prepared
      from aqueous Aloe vera gel and aceclofenac emulsion. The prepared transemulgel
      was evaluated for its pH, viscosity, drug content, skin irritation, in-vitro
      diffusion and accelerated stability studies. The prepared aceclofenac-Aloe vera
      tranemulgel and commercial aceclofenac gel were subjected to pharmacodynamic
      studies in albino rats of Wistar strain employing carrageenan induced left hind
      paw edema method to assess the anti-inflammatory effect. The transemulgel showed
      a pH of 6.78 and viscosity of 18 cps. In-vitro diffusion data revealed better
      permeation characteristics. Topical application of formulation found no skin
      irritation. Stability study has proved the integrity of the formulation. The
      prepared aceclofenac Aloe vera transemulgel showed better in-vitro drug release
      when compared with the commercial aceclofenac gel formulation. Anti-inflammatory
      activity in treated rats showed the significant paw volume reduction at p<0.05
      compared with that of control. Thus, it is concluded that aceclofenac, a
      potential non steroidal anti inflammatory drug, showed high therapeutic
      efficiency when formulated into transemulgel using aqueous Aloe vera as gel base.

PMID- 25751658
TI  - In silico analysis of usher encoding genes in Klebsiella pneumoniae and
      characterization of their role in adhesion and colonization.
AB  - Chaperone/usher (CU) assembly pathway is used by a wide range of
      Enterobacteriaceae to assemble adhesive surface structures called pili or
      fimbriae that play a role in bacteria-host cell interactions. In silico analysis
      revealed that the genome of Klebsiella pneumoniae LM21 harbors eight chromosomal
      CU loci belonging to gammakappap and ? clusters. Of these, only two correspond to
      previously described operons, namely type 1 and type 3-encoding operons. Isogenic
      usher deletion mutants of K. pneumoniae LM21 were constructed for each locus and
      their role in adhesion to animal (Intestine 407) and plant (Arabidopsis thaliana)
      cells, biofilm formation and murine intestinal colonization was investigated.
      Type 3 pili usher deleted mutant was impaired in all assays, whereas type 1 pili
      usher deleted mutant only showed attenuation in adhesion to plant cells and in
      intestinal colonization. The LM21DeltakpjC mutant was impaired in its capacity to
      adhere to Arabidopsis cells and to colonize the murine intestine, either alone or
      in co-inoculation experiments. Deletion of LM21kpgC induced a significant
      decrease in biofilm formation, in adhesion to animal cells and in colonization of
      the mice intestine. The LM21?kpaC and LM21?kpeC mutants were only attenuated in
      biofilm formation and the adhesion abilities to Arabidopsis cells, respectively.
      No clear in vitro or in vivo effect was observed for LM21?kpbC and LM21?kpdC
      mutants. The multiplicity of CU loci in K. pneumoniae genome and their specific
      adhesion pattern probably reflect the ability of the bacteria to adhere to
      different substrates in its diverse ecological niches. 

PMID- 25751660
TI  - Nanotextured pillars of electrosprayed bismuth vanadate for efficient
      photoelectrochemical water splitting.
AB  - We demonstrate, for the first time, electrostatically sprayed bismuth vanadate
      (BiVO4) thin films for photoelectrochemical water splitting. Characterization of
      these films by X-ray diffraction, Raman scattering, and high-resolution scanning
      electron microscopy analyses revealed the formation of nanotextured pillar-like
      structures of highly photoactive monoclinic scheelite BiVO4. Electrosprayed BiVO4
      nanostructured films yielded a photocurrent density of 1.30 and 1.95 mA/cm(2) for
      water and sulfite oxidation, respectively, under 100 mW/cm(2) illumination. The
      optimal film thickness was 3 MUm, with an optimal postannealing temperature of
      550  degrees C. The enhanced photocurrent is facilitated by formation of pillar
      like structures in the deposit. We show through modeling that these structures
      result from the electrically-driven motion of submicron particles in the
      direction parallel to the substrate, as they approach the substrate, along with
      Brownian diffusion. At the same time, opposing thermophoretic forces slow their
      approach to the surface. The model of these processes proposed here is in good
      agreement with the experimental observations. 

PMID- 25751661
TI  - Antipsychotic switching in schizoaffective disorder: A systematic review.
AB  - OBJECTIVES: To systematically review the evidence about the switching of
      antipsychotics in SZA in acute and maintenance treatment. METHODS: A systematic
      review following the PRISMA statement identifying studies specifically conducted
      on, or including, SZA patients. RESULTS: One analysis considered uniquely a SZA
      population, 13 more studies including an adequate SZA subsample were considered.
      Most of the studies were aimed at switching antipsychotic treatments to improve
      tolerability issues. Despite the absolute lack of trials specifically conducted
      on SZA populations, we found limited evidence on the use of aripiprazole,
      lurasidone, and, to a lesser extent, risperidone and ziprasidone as possible
      agents to substitute previous treatments whereas efficacy or, more frequently,
      tolerability issues arise. Evidence supports also the switch to risperidone long
      acting injectable when the adherence to oral treatment may be a concern.
      CONCLUSIONS: Antipsychotic switching in SZA is a neglected topic that would need
      better profiling. Clinicians should keep in mind the receptor binding
      characteristics of drugs in order to optimize transitions. Evidence supports the
      switch to aripiprazole and lurasidone, less strongly to risperidone and
      ziprasidone. The switch to risperidone long-acting injectable is supported,
      especially in patients with limited treatment adherence to oral therapy.

PMID- 25751662
TI  - Synthesis, biological activity, and conformational study of N-methylated
      allatostatin analogues inhibiting juvenile hormone biosynthesis.
AB  - An allatostatin (AST) neuropeptide mimic (H17) is a potential insect growth
      regulator, which inhibits the production of juvenile hormone (JH) by the corpora
      allata. To determine the effect of conformation of novel AST analogues and their
      ability to inhibit JH biosynthesis, eight insect AST analogues were synthesized
      using H17 as the lead compound by N-methylation scanning, which is a common
      strategy for improving the biological properties of peptides. A bioassay using JH
      production by corpora allata of the cockroach Diploptera punctata indicated that
      single N-methylation mimics (analogues 1-4) showed more activity than double N
      methylation mimics (analogues 5-8). Especially, analogues 1 and 4 showed roughly
      equivalent activity to that of H17, with IC50 values of 5.17 * 10(-8) and 6.44 *
      10(-8) M, respectively. Molecular modeling based on nuclear magnetic resonance
      data showed that the conformation of analogues 1 and 4 seems to be flexible,
      whereas analogues 2 and 3 showed a type IV beta-turn. This flexible linear
      conformation was hypothesized to be a new important and indispensable structural
      element beneficial to the activity of AST mimics. 

PMID- 25751663
TI  - Exposure Characteristics of Nanoparticles as Process By-products for the
      Semiconductor Manufacturing Industry.
AB  - This study aims to elucidate the exposure properties of nanoparticles (NPs; <100
      nm in diameter) in semiconductor manufacturing processes. The measurements of
      airborne NPs were mainly performed around process equipment during fabrication
      processes and during maintenance. The number concentrations of NPs were measured
      using a water-based condensation particle counter having a size range of 10-3,000
      nm. The chemical composition, size, and shape of NPs were determined by scanning
      electron microscopy and transmission electron microscopy techniques equipped with
      energy dispersive spectroscopy. The resulting concentrations of NPs ranged from
      0.00-11.47 particles/cm(3). The concentration of NPs measured during maintenance
      showed a tendency to increase, albeit incrementally, compared to that measured
      during normal conditions (under typical process conditions without maintenance).
      However, the increment was small. When comparing the mean number concentration
      and standard deviation (n +/- sigma) of NPs, the chemical mechanical polishing
      (CMP) process was the highest (3.45 +/- 3.65 particles/cm(3)), and the dry etch
      (ETCH) process was the lowest (0.11 +/- 0.22 particles/cm(3)). The major NPs
      observed were silica (SiO2) and titania (TiO2) particles, which were mainly
      spherical agglomerates ranging in size from 25-280 nm. Sampling of semiconductor
      processes in CMP, chemical vapor deposition, and ETCH reveled NPs were <100 nm in
      those areas. On the other hand, particle size exceeded 100 nm in diffusion,
      metallization, ion implantation, and wet cleaning/etching process. The results
      show that the SiO2 and TiO2 are the major NPs present in semiconductor cleanroom
      environments. 

PMID- 25751664
TI  - Mapping of contributions from collateral ligaments to overall knee joint
      constraint: an experimental cadaveric study.
AB  - Understanding the contribution of the soft-tissues to total joint constraint
      (TJC) is important for predicting joint kinematics, developing surgical
      procedures, and increasing accuracy of computational models. Previous studies on
      the collateral ligaments have focused on quantifying strain and tension
      properties under discrete loads or kinematic paths; however, there has been
      little work to quantify collateral ligament contribution over a broad range of
      applied loads and range of motion (ROM) in passive constraint. To accomplish
      this, passive envelopes were collected from nine cadaveric knees instrumented
      with implantable pressure transducers (IPT) in the collateral ligaments. The
      contributions from medial and lateral collateral ligaments (LCL) were quantified
      by the relative contribution of each structure at various flexion angles (0-120
      deg) and compound external loads (+/-10 N m valgus, +/-8 N m external, and +/-40
      N anterior). Average medial collateral ligament (MCL) contributions were highest
      under external and valgus torques from 60 deg to 120 deg flexion. The MCL showed
      significant contributions to TJC under external torques throughout the flexion
      range. Average LCL contributions were highest from 0 deg to 60 deg flexion under
      external and varus torques, as well as internal torques from 60 deg to 110 deg
      flexion. Similarly, these regions were found to have statistically significant
      LCL contributions. Anterior and posterior loads generally reduced collateral
      contribution to TJC; however, posterior loads further reduced MCL contribution,
      while anterior loads further reduced LCL contribution. These results provide
      insight to the functional role of the collaterals over a broad range of passive
      constraint. Developing a map of collateral ligament contribution to TJC may be
      used to identify the effects of injury or surgical intervention on soft-tissue,
      and how collateral ligament contributions to constraint correlate with activities
      of daily living. 

PMID- 25751665
TI  - Heart-type fatty acid binding protein (H-FABP) in patients in an emergency
      department setting, suspected of acute coronary syndrome: optimal cut-off point,
      diagnostic value and future opportunities in primary care.
AB  - BACKGROUND: Most patients presenting chest complaints in primary care are
      referred to secondary care facilities, whereas only a few are diagnosed with
      acute coronary syndrome (ACS). OBJECTIVE: The aim is to determine the optimal cut
      off value for a point-of-care heart-type fatty acid binding protein (H-FABP) test
      in patients presenting to the emergency department and to evaluate a possible
      future role of H-FABP in safely ruling out ACS in primary care. METHODS: Serial
      plasma H-FABP (index test) and high sensitivity troponin T (hs-cTnT) (reference
      test) were determined in patients with any new-onset chest complaint. In a
      receiver operating characteristic (ROC) curve, the optimal cut-off value of H
      FABP for ACS was determined. Predictive values of H-FABP for ACS were calculated.
      RESULTS: For 202 consecutive patients (prevalence ACS 59%), the ROC curve based
      on the results of the first H-FABP was equal to the ROC curve of hs-cTnT (AUC
      0.79 versus 0.80). Using a cut-off value of 4.0 ng/ml for H-FABP, sensitivity for
      ACS of the H-FABP (hs-cTnT) tests was 73.9% (70.6%). Negative predictive value
      (NPV) of H-FABP for ACS in a population representative for primary care
      (incidence of ACS 22%) thus could reach 90.8%. CONCLUSION: In patients presenting
      chest pain, plasma H-FABP reaches the highest diagnostic value when a cut-off
      value of 4 ng/ml is used. Diagnostic values of an algorithm combining point-of
      care H-FABP measurement and a score of signs and symptoms should be studied in
      primary care, to learn if such an algorithm could safely reduce referral rate by
      GPs.

PMID- 25751666
TI  - Histomorphometric assessment of the influence of low-level laser therapy on peri
      implant tissue healing in the rabbit mandible.
AB  - OBJECTIVE: The purpose of this study was to demonstrate the effect of low-level
      laser therapy (LLLT) on the peri-implant bone healing process in the rabbit
      mandible. BACKGROUND DATA: LLLT has been shown to accelerate tissue repair and
      osseointegration of implants placed into the rabbit tibia. However, the
      beneficial effects of LLLT have never been tested in the rabbit mandible, which
      would more closely mimic the human situation. MATERIALS AND METHODS: Twenty-four
      male New Zealand rabbits were randomly divided into four groups of six animals
      each. All animals had their left mandibular incisors extracted, followed by
      immediate insertion of a titanium dental implant in the fresh socket. Three
      groups received LLLT [aluminum-gallium-arsenide (AlGaAs), lambda=830nm, 50 mW,
      continuous wave (CW)] at three different energy densities per treatment session
      (E-5, 5 J/cm(2); E-10, 10 J/cm(2); and E-20, 20 J/cm(2)). Irradiation was
      performed every 48 h for 13 days, totaling seven sessions. One group received
      sham treatment (controls). Histological sections were obtained from each of the
      24 mandibles dissected, without first decalcifying the specimens, and were
      stained with hematoxylin and eosin and Picrosirius red for histomorphometric
      evaluation. Bone-to-implant contact (BIC), bone formation area, and collagen
      fiber area were assessed by light microscopy. RESULTS: Significant differences
      were found between group E-20 and all other groups (p<0.05). Histomorphometric
      evaluation showed significantly higher BIC and significantly more collagen fibers
      in group E-20. CONCLUSIONS: Photobiostimulation with LLLT at an energy density of
      20 J/cm(2) per session had a significant positive effect on new bone formation
      around dental implants inserted in the rabbit mandible.

PMID- 25751667
TI  - Effect of MLS((r)) laser therapy with different dose regimes for the treatment of
      experimentally induced tendinopathy in sheep: pilot study.
AB  - OBJECTIVE: The aim of this preliminary study was to investigate the effect of
      Multiwave Locked System (MLS((r))), a particular model of low-level laser, in the
      acute phase of collagenase-induced tendon lesions in six adult sheep randomly
      assigned to two groups. BACKGROUND DATA: Tendon injuries are common among human
      athletes and in sport horses, require a long recovery time, and have a high risk
      of relapse. Many traditional treatments are not able to repair the injured tendon
      tissue correctly. In recent years, the use of low-level laser therapy (LLLT)
      produced interesting results in inflammatory modulation in different
      musculoskeletal disorders. METHODS: Group 1 received 10 treatments of MLS laser
      therapy at a fluence of 5 J/cm(2) on the left hindlimb. Group 2 received 10
      treatments of MLS laser therapy at a fluence of 2.5 J/cm(2) on the left hindlimb.
      In every subject in both groups, the right hindlimb was considered as the control
      leg. RESULTS: Clinical follow-up and ultrasonography examinations were performed
      during the postoperative period, and histological examinations were performed at
      day 30 after the first application of laser therapy. In particular, results from
      histological examinations indicate that both treatments induced a statistically
      significant cell number decrease, although only in the second group did the
      values return to normal. Moreover, the MLS laser therapy dose of 2.5 J/cm(2)
      (group 2) caused a significant decrease of vessel area. CONCLUSIONS: In this
      study, clinical and histological evaluation demonstrated that a therapeutic dose
      <5 J/cm(2) furnished an anti-inflammatory effect, and induced a decrease of
      fibroblasts and vessel area. Overall, our results suggest that MLS laser therapy
      was effective in improving collagen fiber organization in the deep digital flexor
      tendon.

PMID- 25751668
TI  - The Endoplasmic Reticulum Resident Protein AGR3. Required for Regulation of
      Ciliary Beat Frequency in the Airway.
AB  - Protein disulfide isomerase (PDI) family members regulate protein folding and
      calcium homeostasis in the endoplasmic reticulum (ER). The PDI family member
      anterior gradient (AGR) 3 is expressed in the airway, but the localization,
      regulation, and function of AGR3 are poorly understood. Here we report that AGR3,
      unlike its closest homolog AGR2, is restricted to ciliated cells in the airway
      epithelium and is not induced by ER stress. Mice lacking AGR3 are viable and
      develop ciliated cells with normal-appearing cilia. However, ciliary beat
      frequency was lower in airways from AGR3-deficient mice compared with control
      mice (20% lower in the absence of stimulation and 35% lower after ATP
      stimulation). AGR3 deficiency had no detectable effects on ciliary beat frequency
      (CBF) when airways were perfused with a calcium-free solution, suggesting that
      AGR3 is required for calcium-mediated regulation of ciliary function. Decreased
      CBF was associated with impaired mucociliary clearance in AGR3-deficient airways.
      We conclude that AGR3 is a specialized member of the PDI family that plays an
      unexpected role in the regulation of CBF and mucociliary clearance in the airway.

PMID- 25751669
TI  - Low-voltage flexible organic electronics based on high-performance sol-gel
      titanium dioxide dielectric.
AB  - In this letter, we report that high-performance insulating films can be generated
      by judicious control over the microstructure of sol-gel-processed titanium
      dioxide (TiO2) films, typically known as wide-bandgap semiconductors. The
      resultant device made of 23 nm-thick TiO2 dielectric layer exhibits a low leakage
      current density of ~1 * 10(-7) A cm(-2) at 2 V and a large areal capacitance of
      560 nF cm(-2) with the corresponding dielectric constant of 27. Finally, low
      voltage flexible organic thin-film transistors were successfully demonstrated by
      incorporating this versatile solution-processed oxide dielectric material into
      pentacene transistors on polyimide substrates. 

PMID- 25751670
TI  - Recent developments in clinical trial designs for HIV vaccine research.
AB  - HIV vaccine strategies are expected to be a crucial component for controlling the
      HIV epidemic. Despite the large spectrum of potential candidate vaccines for both
      prophylactic and therapeutic use, the overall development process of an
      efficacious HIV vaccine strategy is lengthy. The design of clinical trials and
      the progression of a candidate strategy through the different clinical
      development stages remain methodologically challenging, mainly due to the lack of
      validated correlates of protection. In this review, we describe recent advances
      in clinical trial designs to increase the efficiency of the clinical development
      of candidate HIV vaccine strategies. The methodological aspects of the designs
      for early- (phase I and II) and later -stage (phase IIB and III) development are
      discussed, taking into account the specificities of both prophylactic and
      therapeutic HIV vaccine development. 

PMID- 25751671
TI  - Induction of CD44 variant 9-expressing cancer stem cells might attenuate the
      efficacy of chemoradioselection and Worsens the prognosis of patients with
      advanced head and neck cancer.
AB  - BACKGROUND: At our institute, a chemoradioselection strategy has been used to
      select patients for organ preservation on the basis of response to an initial 30
      40 Gy concurrent chemoradiotherapy (CCRT). Patients with a favorable response
      (i.e., chemoradioselected; CRS) have demonstrated better outcomes than those with
      an unfavorable response (i.e., nonchemoradioselected; N-CRS). Successful
      targeting of molecules that attenuate the efficacy of chmoradioselection may
      improve results. Thus, the aim of this study was to evaluate the association of a
      novel cancer stem cell (CSC) marker, CD44 variant 9 (CD44v9), with cellular
      refractoriness to chemoradioselection in advanced head and neck squamous cell
      carcinoma (HNSCC). MATERIALS AND METHODS: Through a medical chart search, 102
      patients with advanced HNSCC treated with chemoradioselection from 1997 to 2008
      were enrolled. According to our algorithm, 30 patients were CRC following
      induction CCRT and 72 patients were N-CRS. Using the conventional
      immunohistochemical technique, biopsy specimens and surgically removed tumor
      specimens were immunostained with the anti-CD44v9 specific antibodies. RESULTS:
      The intrinsic expression levels of CD44v9 in the biopsy specimens did not
      correlate with the chemoradioselection and patient survival. However, in N-CRS
      patients, the CD44v9-positive group demonstrated significantly (P = 0.008) worse
      prognosis, than the CD44v9-negative group. Multivariate analyses demonstrated
      that among four candidate factors (T, N, response to CCRT, and CD44v9), CD44v9
      positivity (HR: 3.145, 95% CI: 1.235-8.008, P = 0.0163) was significantly
      correlated with the poor prognosis, along with advanced N stage (HR: 3.525, 95%
      CI: 1.054-9.060, P = 0.0228). Furthermore, the survival rate of the CD44v9
      induced group was significantly (P = 0.04) worse than the CD44v9-non-induced
      group. CONCLUSIONS: CCRT-induced CD44v9-expressing CSCs appear to be a major
      hurdle to chemoradioselection. CD44v9-targeting seems to be a promising strategy
      to enhance the efficacy of chemoradioselection and consequent organ preservation
      and survival.

PMID- 25751672
TI  - NF-kappaB Regulation of c-FLIP Promotes TNFalpha-Mediated RAF Inhibitor
      Resistance in Melanoma.
AB  - Targeted inhibitors elicit heterogeneous clinical responses in genetically
      stratified groups of patients. Although most studies focus on tumor intrinsic
      properties, factors in the tumor microenvironment were recently found to modulate
      the response to inhibitors. Here, we show that in cutaneous BRAF V600E melanoma,
      the cytokine tumor necrosis factor-alpha (TNFalpha) blocks RAF inhibitor-induced
      apoptosis via activation of NF-kappaB. Several NF-kappaB-dependent factors are
      upregulated following TNFalpha and RAF inhibitor treatment. Of these factors, we
      show that death receptor inhibitor cellular caspase 8 (FLICE)-like inhibitory
      protein (c-FLIP) is required for TNFalpha-induced protection against RAF
      inhibitor. Overexpression of c-FLIP_S or c-FLIP_L isoform decreased RAF inhibitor
      induced apoptosis in the absence of TNFalpha. Importantly, targeting NF-kappaB
      enhances response to RAF inhibitor in vitro and in vivo. Together, our results
      show mechanistic evidence for cytokine-mediated resistance to RAF inhibitor and
      provide a preclinical rationale for the strategy of cotargeting the
      RAF/MEK/ERK1/2 pathway and the TNFalpha/NF-kappaB axis to treat mutant BRAF
      melanomas. 

PMID- 25751673
TI  - Comparison of isotonic and hypotonic intravenous maintenance fluids: a randomized
      clinical trial.
AB  - IMPORTANCE: Use of hypotonic intravenous fluids for maintenance requirements is
      associated with increased risk of hyponatremia that results in morbidity and
      mortality in children. Clinical trial data comparing isotonic and hypotonic
      maintenance fluids in nonsurgical hospitalized pediatric patients outside
      intensive care units are lacking. OBJECTIVE: To compare isotonic (sodium
      chloride, 0.9%, and dextrose, 5%) with hypotonic (sodium chloride, 0.45%, and
      dextrose, 5%) intravenous maintenance fluids in a hospitalized general pediatric
      population. DESIGN, SETTING, AND PARTICIPANTS: In this double-blind randomized
      clinical trial,we recruited 110 children admitted to a general pediatric unit of
      a tertiary care children's hospital from March 1, 2008, through August 31, 2012
      (age range, 1 month to 18 years), with normal baseline serum sodium levels who
      were anticipated to require intravenous maintenance fluids for 48 hours or longer
      (intent-to-treat analyses). Children with diagnoses that required specific fluid
      tonicity and volumes were excluded. INTERVENTIONS: Patients were randomized to
      receive isotonic or hypotonic intravenous fluid at maintenance rates for 48
      hours. MAIN OUTCOMES AND MEASURES: The primary outcome was mean serum sodium
      level at 48 hours. The secondary outcomes were mean sodium level at 24 hours,
      hyponatremia and hypernatremia, weight gain, hypertension, and edema. Confounding
      variables were included in multiple regression models. Post hoc analyses included
      change from baseline sodium level at 24 and 48 hours and subgroup analysis of
      children with primary respiratory diagnosis. RESULTS: Of 110 enrolled patients,
      54 received isotonic fluids and 56 received hypotonic fluids. The mean (SD)
      sodium level at 48 hours was 139.9 (2.7) mEq/L in the isotonic group and 139.6
      (2.6) mEq/L in the hypotonic group (95% CI of the difference, -0.94 to 1.74
      mEq/L; P = .60). Two patients in the hypotonic group developed hyponatremia, 1 in
      each group developed hypernatremia, 2 in each group developed hypertension, and 2
      in the isotonic group developed edema. Mean (SD) change from baseline to 48-hour
      sodium level was +1.3 (2.9) vs -0.12 (2.8) mEq/L, respectively (absolute
      difference, 1.4 mEq/L; 95% CI of the difference, -0.01 to 2.8 mEq/L; P = .05).
      CONCLUSIONS AND RELEVANCE: Our study results support the notion that isotonic
      maintenance fluid administration is safe in general pediatric patients and may
      result in fewer cases of hyponatremia. TRIAL REGISTRATION: clinicaltrials.gov
      Identifier: NCT00632775.

PMID- 25751675
TI  - Effect of structure on the tribology of ultrathin graphene and graphene oxide
      films.
AB  - The friction and wear properties of graphene and graphene oxide (GO) with varying
      C/O ratio were investigated using friction force microscopy. When applied as
      solid lubricants between a sliding contact of a silicon (Si) tip and a SiO2/Si
      substrate, graphene and ultrathin GO films (as thin as 1-2 atomic layers) were
      found to reduce friction by ~6 times and ~2 times respectively as compared to the
      unlubricated contact. The differences in measured friction were attributed to
      different interfacial shear strengths. Ultrathin films of GO with a low C/O ratio
      of ~2 were found to wear easily under small normal load. The onset of wear, and
      the location of wear initiation, is attributed to differences in the local shear
      strength of the sliding interface as a result of the non-homogeneous surface
      structure of GO. While the exhibited low friction of GO as compared to SiO2 makes
      it an economically viable coating for micro/nano-electro-mechanical systems with
      the potential to extend the lifetime of devices, its higher propensity for wear
      may limit its usefulness. To address this limitation, the wear resistance of GO
      samples with a higher C/O ratio (~4) was also studied. The higher C/O ratio GO
      was found to exhibit much improved wear resistance which approached that of the
      graphene samples. This demonstrates the potential of tailoring the structure of
      GO to achieve graphene-like tribological properties. 

PMID- 25751674
TI  - The capability of Pseudomonas aeruginosa to recruit zinc under conditions of
      limited metal availability is affected by inactivation of the ZnuABC transporter.
AB  - The ability of a large number of bacterial pathogens to multiply in the infected
      host and cause disease is dependent on their ability to express high affinity
      zinc importers. In many bacteria, ZnuABC, a transporter of the ABC family, plays
      a central role in the process of zinc uptake in zinc poor environments, including
      the tissues of the infected host. To initiate an investigation into the relevance
      of the zinc uptake apparatus for Pseudomonas aeruginosa pathogenicity, we have
      generated a znuA mutant in the PA14 strain. We have found that this mutant strain
      displays a limited growth defect in zinc depleted media. The znuA mutant strain
      is more sensitive than the wild type strain to calprotectin-mediated growth
      inhibition, but both the strains are highly resistant to this zinc sequestering
      antimicrobial protein. Moreover, intracellular zinc content is not evidently
      affected by inactivation of the ZnuABC transporter. These findings suggest that
      P. aeruginosa is equipped with redundant mechanisms for the acquisition of zinc
      that might favor P. aeruginosa colonization of environments containing low levels
      of this metal. Nonetheless, deletion of znuA affects alginate production, reduces
      the activity of extracellular zinc-containing proteases, including LasA, LasB and
      protease IV, and decreases the ability of P. aeruginosa to disseminate during
      systemic infections. These results indicate that efficient zinc acquisition is
      critical for the expression of various virulence features typical of P.
      aeruginosa and that ZnuABC also plays an important role in zinc homeostasis in
      this microorganism. 

PMID- 25751676
TI  - Building pH sensors into paper-based small-molecular logic systems for very
      simple detection of edges of objects.
AB  - Genetically engineered bacteria and reactive DNA networks detect edges of
      objects, as done in our retinas and as also found within computer vision. We now
      demonstrate that simple molecular logic systems (a combination of a pH sensor, a
      photo acid generator, and a pH buffer spread on paper) without any organization
      can achieve this relatively complex computational goal with good fidelity. This
      causes a jump in the complexity achievable by molecular logic-based computation
      and extends its applicability. The molecular species involved in light dose
      driven "off-on-off" fluorescence is diverted in the "on" state by proton
      diffusion from irradiated to unirradiated regions where it escapes a strong
      quencher, thus visualizing the edge of a mask. 

PMID- 25751677
TI  - Adjunctive therapies for treatment of severe respiratory failure in neonates.

PMID- 25751678
TI  - [Middle ear drainage and ventilation: indications, complications and their
      treatment].
AB  - Tympanostomy is the most frequently performed surgery procedure in Germany. It
      enables middle ear ventilation and discharge of secretion from the middle ear
      with immediate hearing improvement and avoidance of complications and long-term
      pathologies of the tympanic membrane and the tympanum. The economical importance
      is emphasized by the fact that about 300,000 myringotomies are performed yearly.
      The best type of middle ear drainage and ventilation should be chosen on a case
      by-case basis. In this context, the various techniques like conventional
      myringotomy, laser-myringotomy, short-term and long-term tympanostomy tubes and
      indications, complications and their treatments are described.

PMID- 25751679
TI  - Septic shock in children in an urban area in Western Germany--outcome, risk
      factors for mortality and infection epidemiology.
AB  - BACKGROUND: Only sparse data exist about children with septic shock in Europe.
      The present study aimed to evaluate demographics, treatment, outcome and risk
      factors for mortality in Western Germany. PATIENTS: Children with septic shock
      aged 2 months to 17 years. METHODS: In a multi-center retrospective study of 20
      children's hospitals data were obtained and analyzed by chart review. Risk
      factors for mortality were identified and assessed by multivariate regression
      analysis. RESULTS: Overall mortality in 83 cases with septic shock was 25% (21
      patients). Significant risk factors were high PRISM III score, low pH, low
      arterial systolic blood pressure, presence of disseminated intravascular
      coagulation and extent of multi-organ failure, but not lactate (p=0.05) and base
      excess (p=0.065). Mortality in hospitals which treated 10 or more patients
      (category 1) was 17% and increased to 22% in hospitals which treated 3-6 patients
      (category 2). In hospitals with only 1 or 2 patients (category 3) mortality rate
      was 61% (p<0.01 when compared to category 1 or 2). A stepwise increase was also
      seen in the severely sick patients according to PRISM III (>19): category 1: 23%,
      category 2: 40%, category 3: 62.5% (p<0.05 for comparison of category 1 and 3).
      Multivariate analysis of significant risk factors revealed low number of treated
      patients as the only individual risk factor for mortality. CONCLUSION: Mortality
      from pediatric septic shock in an urban area in Western Germany is high. Disease
      severity and treatment in a department with few cases were associated with
      increased mortality.

PMID- 25751680
TI  - [Indications and concept of follow-up care of home-monitoring for premature and
      risk infants].
AB  - The pros and cons of home monitoring especially for premature infants with
      continuing apneic episodes and/or chronic lung disease are an ongoing discussion.
      The controversy spans socio-economic requirements, medical indication as well as
      patient and family needs. Here, the costs of home monitoring and follow-up care
      on the one hand and longer hospitalization times on the other need to be
      considered. This article aims to create a basis for this discussion by
      summarizing current evidence for the indications and considerations for
      differential diagnoses while also outlining the established follow-up program for
      these patients at the Dr. v. Hauner Children's Hospital at the Ludwig-Maximilians
      University Munich, Germany. 

PMID- 25751681
TI  - Increased risk for bronchitis after discharge in non-vaccinated very low birth
      weight infants.
AB  - BACKGROUND: In very low birth weight (VLBW) infants, obstructive bronchitis is a
      frequent cause of hospital re-admission. For VLBW infants, early vaccinations
      starting at 2 months after birth have been recommended. OBJECTIVE: To analyze
      risk factors for bronchitis during the first year after discharge and the effects
      of in-hospital standard vaccination (hexavalent/pneumococci) and/or RSV
      immunoprophylaxis with palivizumab. METHODS: A standardized questionnaire was
      sent to the parents of VLBW infants 7 month after discharge. The reported
      episodes of bronchitis were correlated with clinically recorded parameters
      including risk factors for pulmonary morbidity. The effects of in-hospital
      vaccination were assessed in a subgroup discharged after day 60. RESULTS: A
      sample of 1 967 responses of infants born 2009-2011 was analyzed. Risk factors
      for bronchitis were male gender and older siblings. 24% of the population had
      episodes of bronchitis. In the subgroup discharged after day 60, episodes of
      bronchitis were reported for 31% of infants who were not vaccinated in-hospital.
      A significant reduction of the bronchitis rate was found in infants who received
      palivizumab+/-standard vaccination (17% bronchitis, p=0.003). Interestingly, in
      hospital standard vaccination without RSV immunoprophylaxis was protective (20%
      bronchitis; p=0.037) as well. CONCLUSIONS: Non-vaccinated male VLBW infants with
      older siblings are at increased risk for bronchitis during the first year after
      discharge. Vaccination according to schedule seems to have protective effects,
      while underlying mechanisms are unknown. The rate of timely vaccination in
      preterm infants should be increased.

PMID- 25751682
TI  - Recurrent infective endocarditis due to Aggregatibacter aphrophilus and
      Staphylococcus lugdunensis.
AB  - Uncommon microorganisms are increasingly being recognized as causative agents of
      paediatric infectious endocarditis (IE). We report a 4-year old girl with
      congenital heart disease, who suffered from 2 IE episodes secondary to
      Aggregatibacter aphrophilus (formerly Haemophilus aphrophilus) and Staphylococcus
      lugdunensis, both rarely reported pathogens in this age group. The patient was
      initially successfully treated with prolonged intravenous antibiotic courses,
      however removal of the Contegra valved conduit during the second episode was
      required due to recurrence of fever and development of pulmonary embolism despite
      completion of antibiotic therapy. A. aphrohilus is a member of the fastidious
      gram negative microorganisms of the HACEK group (Haemophilus spp.,
      Aggregatibacter spp, Cardiobaterium hominis, Eikenella corrodens and Kingella
      kingae), that colonize the oropharynx and are a recognised cause of IE. Prognosis
      of children with IE due to HACEK group members varies, half of them suffering
      from complications and mortality rates of 10-12.5%. Although S. lugdunensis
      belongs to coagulase negative staphylococci (CONS), it behaves more like S.
      aureus species rather than CONS. This microorganism is a well-described cause of
      endocarditis in adult patients, associated with high requirements of surgical
      procedures and mortality (42-78%). In conclusion, paediatric IE can be caused by
      uncommon microorganisms associated with severe complications and potential
      fatality. The isolation of S. lugdunensis or A. aphrophilus in febrile patients
      should be considered clinically relevant and cardiac involvement must be ruled
      out. Those patients with proved IE will require prolonged intravenous antibiotic
      courses and in complicated cases surgical intervention. 

PMID- 25751683
TI  - [Tracheoesophageal fistula after button battery ingestion--esophagography as
      effective diagnostic examination].

PMID- 25751684
TI  - Prominent crista terminalis in the neonatal period.

PMID- 25751685
TI  - Misdiagnosis of cystic fibrosis based on transient pancreatic insufficiency and
      elevated sweat chloride.

PMID- 25751686
TI  - Competitive volumetric bar-chart chip with real-time internal control for point
      of-care diagnostics.
AB  - Point-of-care (POC) testing has become widely used in clinical analysis because
      of its speed and portability; however, POC tools, such as lateral flow assays,
      suffer from low specificity, unclear readouts, and susceptibility to
      environmental and user errors. Herein, we report an ELISA-based competitive
      volumetric bar-chart chip (CV-chip) that eliminates these limitations. The CV
      chip displays the readout in the form of ink bar charts based on direct
      competition between gases generated by the sample and the internal control. By
      employing a "competition mode", this platform decreases the potential influence
      of background resulting from environmental factors and provides visually clear
      positive or negative results without the requirement of calibration. In addition,
      the on-chip comparison enables the device to distinguish imperceptible
      differences (less than 1.3-fold) in human chorionic gonadotropin (hCG)
      concentrations that are near the cutoff value for pregnancy (~1.4 ng/mL). We also
      utilized the ELISA-based CV-chip to successfully detect biomarkers from cancer
      cells. As a proof-of-concept application in a clinical setting, the CV-chip was
      employed to evaluate the status of drugs of abuse in 18 patients. For six
      different drugs, zero false-positive and very few false-negative (<2%) results
      were reported in more than 100 tests. This new ELISA platform offers a clinical
      diagnostics tool that is portable and easy to use, and provides improved clarity
      and sensitivity due to the inclusion of a real-time internal control. 

PMID- 25751687
TI  - Self-regulation in the era of big data: appropriate use of appropriate use
      criteria.

PMID- 25751688
TI  - Exploring the implications of a fixed budget for new medicines: a study of
      reimbursement of new medicines in Australia and New Zealand.
AB  - OBJECTIVE: Spending on medicines under the Pharmaceutical Benefits Scheme (PBS)
      represents the ninth largest expense to the Federal Government. A recent report
      by the Commission of Audit to the Federal Government suggested spending on the
      PBS is unsustainable and a capped budget, similar to New Zealand's PHARMAC model,
      may be required to contain costs. The objective of the present study was to
      compare listing outcomes between Australia and New Zealand, thereby exploring the
      opportunity cost of a capped budget for new medicines. METHODS: Listing outcomes
      in Australia and New Zealand were compared through published research and an
      updated search of listing outcomes from publicly available information. RESULTS:
      Previous research has demonstrated that New Zealand listed less than half of the
      new medicines listed in Australia over a 10-year period (2000-09). Our research
      shows that most of the new medicines not listed in New Zealand during this period
      remain unlisted today. In the previous 12 months, Australia listed 17 new
      medicines on the PBS, whereas New Zealand listed only one new medicine that was
      not already listed in Australia. CONCLUSION: The discrepancy in the number of new
      medicines listed in New Zealand compared with Australia raises questions
      regarding the consequences of implementing a capped budget for new medicines.
      However, further research is needed to understand the relationship between
      listing outcomes, access to medicines and health benefits for the community.

PMID- 25751690
TI  - 2015 JAAA Editor's Award.

PMID- 25751689
TI  - Confessions of an audiology "legacy".

PMID- 25751691
TI  - The effect of background babble on working memory in young and middle-aged
      adults.
AB  - BACKGROUND: Background noise has been found to negatively affect working memory.
      Numerous studies have also found that older adults perform more poorly on working
      memory tasks than young adults (YA). Hearing status has often been a confounding
      factor in older individuals. Therefore, it would be beneficial to investigate
      working memory functions in adverse listening conditions early in the aging
      process (i.e., middle-age), when hearing function is relatively unaffected.
      PURPOSE: The focus of this study was to determine the influence of background
      babble on working memory in YA and middle-aged adults (MA) with normal hearing.
      RESEARCH DESIGN: Before testing was begun, we established that all participants
      could correctly identify words in a degraded experimental testing environment
      with 100% accuracy. Then, the participants listened to lists composed of five
      pairs of words in quiet and in 20-talker babble. After the final word pair, the
      participants were cued with the first word of one of the previous five word
      pairs. The participants were required to write down the second word of the pair.
      The percent correct scores for each of the five serial positions were analyzed
      comparing the two listening conditions for YA and MA. Ten YA and ten MA with
      normal hearing between 250-8000 Hz and a score of at least 26/30 on the Mini
      Mental State Examination participated in the study. As different cognitive
      processes are used for initial, middle, and final serial positions, averaged
      scores were obtained for Positions 2 and 3 and for Positions 4 and 5.
      Subsequently, repeated-measures analyses of variance (ANOVAs) were conducted on
      mean scores of correctly recalled word pairs with serial positions (initial,
      middle, and final) and listening condition (quiet, babble) as the within
      participant variables and age group (YA, MA) as the between-participant
      independent variable. This OMNIBUS repeated-measures ANOVA was then followed up
      with separate repeated-measures ANOVAS for the initial, middle, and final
      positions. RESULTS: Correct recall scores were lower for early positions compared
      with the latter positions, irrespective of listening condition. For Position 1,
      YA-but not MA-performed significantly better in babble than in quiet. For the
      middle positions (Positions 2 and 3), MA performed significantly more poorly than
      the YA irrespective of listening condition. For the final positions (Positions 4
      and 5), no age differences or effects of listening condition were found.
      CONCLUSIONS: The results indicate that both YA and MA have trouble recalling
      earlier pieces of information in quiet and in babble. However, MA exhibited
      significantly poorer recall scores than YA in babble for Position 1, which
      suggest that cognitive processes related to memory encoding and retrieval are
      different in background babble for MA and YA.

PMID- 25751692
TI  - Case factors affecting hearing aid recommendations by hearing care professionals.
AB  - BACKGROUND: Professional recommendations to patients concerning hearing
      instrument (HI) technology levels are not currently evidence-based. Pre-fitting
      parameters have not been proven to be the primary indicators for optimal patient
      outcome with different HI technology levels. This results in subjective decision
      making as regards the technology level recommendation made by professionals.
      PURPOSE: The objective of this study is to gain insight into the decision-making
      criteria utilized by professionals when recommending HI technology levels to
      hearing-impaired patients. RESEARCH DESIGN: A set of patient variables (and their
      respective levels) was identified by professionals as determinant for their
      recommendation of HIs. An experimental design was developed and 21 representative
      patient cases were generated. The design was based on a contrastive vignette
      technique according to which different types of vignettes (patient cases) were
      randomly presented to respondents in an online survey. Based on these patient
      cases, professionals were asked in the survey to make a treatment recommendation.
      STUDY SAMPLE: The online survey was sent to approximately 3,500 professionals
      from the US, Germany, France, and Italy. The professionals were randomly selected
      from the databases of Oticon sales companies. The manufacturer sponsoring the
      survey remained anonymous and was only revealed after completing the survey, if
      requested by the respondent. The response rate was 20.5%. DATA COLLECTION AND
      ANALYSIS: Data comprised of respondent descriptions and patient case
      recommendations that were collected from the online survey. A binary logit
      modeling approach was used to identify the variables that discriminate between
      the respondents' recommendations of HI technology levels. RESULTS: The results
      show that HI technology levels are recommended by professionals based on their
      perception of the patient's activity level in life, the level of HI usage for
      experienced users, their age, and their speech discrimination score.
      Surprisingly, the patient's lifestyle as perceived by the hearing care
      professional, followed by speech discrimination, were the strongest factors in
      explaining treatment recommendation. An active patient with poor speech
      discrimination had a 17% chance of being recommended the highest technology level
      HI. For a very active patient with good speech discrimination, the probability
      increases to 68%. CONCLUSIONS: The discrepancies in HI technology level
      recommendations are not justified by academic research or evidence of optimal
      patient outcome with a different HI technology level. The paradigm of lifestyle
      as the significant variable identified in this study is apparently deeply
      anchored in the mindset of the professional despite the lack of supporting
      evidence. These results call for a shift in the professional's technology level
      recommendation practice, from nonevidence-based to a proven practice that can
      maximize patient outcome.

PMID- 25751693
TI  - Comparisons of client and clinician views of the importance of factors in client
      clinician interaction in hearing aid purchase decisions.
AB  - BACKGROUND: Despite clinical recognition of the adverse effects of acquired
      hearing loss, only a small proportion of adults who could benefit use hearing
      aids. Hearing aid adoption has been studied in relationship to client-related and
      hearing aid technology-related factors. The influence of the client-clinician
      interaction in the decision to purchase hearing aids has not been explored in any
      depth. PURPOSE: Importance ratings of a sample of adults having a recent hearing
      aid recommendation (clients) and hearing healthcare professionals (clinicians)
      from across Canada were compared on factors in client-clinician interactions that
      influence hearing aid purchase decisions. RESEARCH DESIGN: A cross-sectional
      approach was used to obtain online and paper-based concept ratings. DATA
      COLLECTION AND ANALYSIS: Participants were 43 adults (age range, 45-85 yr) who
      had received a first hearing aid recommendation in the 3 mo before participation.
      A total of 54 audiologists and 20 hearing instrument practitioners from a variety
      of clinical settings who prescribed or dispensed hearing aids completed the
      concept-rating task. The task consisted of 122 items that had been generated via
      concept mapping in a previous study and which resulted in the identification of
      eight concepts that may influence hearing aid purchase decisions. Participants
      rated "the importance of each of the statements in a person's decision to
      purchase a hearing aid" on a 5-point Likert scale, from 1 = minimally important
      to 5 = extremely important. For the initial data analysis, the ratings for each
      of the items included in each concept were averaged for each participant to
      provide an estimate of the overall importance rating of each concept.
      Multivariate analysis of variance was used to compare the mean importance ratings
      of the clients to the clinicians. Ratings of individual statements were also
      compared in order to investigate the directionality of the importance ratings
      within concepts. RESULTS: There was a significant difference in the mean ratings
      for clients and clinicians for the concepts understanding and meeting client
      needs, conveying device information by clinician, supporting choices and shared
      decision making, and factors in client readiness. Three concepts-understanding
      and meeting client needs, conveying device information by clinician, and
      supporting choices and shared decision making-were rated as more important by
      clients than by clinicians. One concept (ie, factors in client readiness) was
      rated as more important by clinicians than by clients. CONCLUSIONS: The concepts
      rated as most important by clients and clinicians are consistent with components
      of several existing models of client-centered and patient-centered care. These
      concepts reflect the clients' perception of the importance of their involvement
      in the decision-making process. A preliminary model of client-centered care
      within the hearing aid uptake process and implications for clinical audiology are
      described.

PMID- 25751694
TI  - Comparing NAL-NL1 and DSL v5 in Hearing Aids Fit to Children with Severe or
      Profound Hearing Loss: Goodness of Fit-to-Targets, Impacts on Predicted Loudness
      and Speech Intelligibility.
AB  - BACKGROUND: An important goal of providing amplification to children with hearing
      loss is to ensure that hearing aids are adjusted to match targets of prescriptive
      procedures as closely as possible. The Desired Sensation Level (DSL) v5 and the
      National Acoustic Laboratories' prescription for nonlinear hearing aids, version
      1 (NAL-NL1) procedures are widely used in fitting hearing aids to children.
      Little is known about hearing aid fitting outcomes for children with severe or
      profound hearing loss. PURPOSE: The purpose of this study was to investigate the
      prescribed and measured gain of hearing aids fit according to the NAL-NL1 and the
      DSL v5 procedure for children with moderately severe to profound hearing loss;
      and to examine the impact of choice of prescription on predicted speech
      intelligibility and loudness. RESEARCH DESIGN: Participants were fit with Phonak
      Naida V SP hearing aids according to the NAL-NL1 and DSL v5 procedures. The
      Speech Intelligibility Index (SII) and estimated loudness were calculated using
      published models. STUDY SAMPLE: The sample consisted of 16 children (30 ears)
      aged between 7 and 17 yr old. DATA COLLECTION AND ANALYSIS: The measured hearing
      aid gains were compared with the prescribed gains at 50 (low), 65 (medium), and
      80 dB SPL (high) input levels. The goodness of fit-to-targets was quantified by
      calculating the average root-mean-square (RMS) error of the measured gain
      compared with prescriptive gain targets for 0.5, 1, 2, and 4 kHz. The
      significance of difference between prescriptions for hearing aid gains, SII, and
      loudness was examined by performing analyses of variance. Correlation analyses
      were used to examine the relationship between measures. RESULTS: The DSL v5
      prescribed significantly higher overall gain than the NAL-NL1 procedure for the
      same audiograms. For low and medium input levels, the hearing aids of all
      children fit with NAL-NL1 were within 5 dB RMS of prescribed targets, but 33% (10
      ears) deviated from the DSL v5 targets by more than 5 dB RMS on average. For high
      input level, the hearing aid fittings of 60% and 43% of ears deviated by more
      than 5 dB RMS from targets of NAL-NL1 and DSL v5, respectively. Greater
      deviations from targets were associated with more severe hearing loss. On
      average, the SII was higher for DSL v5 than for NAL-NL1 at low input level. No
      significant difference in SII was found between prescriptions at medium or high
      input level, despite greater loudness for DSL v5 than for NAL-NL1. CONCLUSIONS:
      Although targets between 0.25 and 2 kHz were well matched for both prescriptions
      in commercial hearing aids, gain targets at 4 kHz were matched for NAL-NL1 only.
      Although the two prescriptions differ markedly in estimated loudness, they
      resulted in comparable predicted speech intelligibility for medium and high input
      levels.

PMID- 25751695
TI  - Speech intelligibility benefits of hearing AIDS at various input levels.
AB  - BACKGROUND: Although the benefits of hearing aids are generally recognized for
      soft- and conversational-level sounds, most studies have reported negative
      benefits (i.e., poorer aided than unaided performance) at high noise inputs.
      Advances in digital signal processing such as compression, noise reduction, and
      directional microphone could improve speech perception at high input levels. This
      could alter our view on the efficacy of hearing aids in loud, noisy situations.
      PURPOSE: The current study compared the aided versus the unaided speech
      intelligibility performance of hearing-impaired (HI) listeners at various input
      levels (from 50-100 dB SPL) and signal-to-noise ratios (SNRs; quiet, +6, +3, and 
      3 dB) in order to document the benefits of modern hearing aids. In addition,
      subjective preference between aided and unaided sounds (speech and music) at
      various input levels was also compared. RESEARCH DESIGN: The experiment used a
      factorial repeated-measures design. STUDY SAMPLE: A total of 10 HI adults with
      symmetrical moderate to severe hearing losses served as test participants. In
      addition, speech intelligibility scores of five normal-hearing (NH) listeners
      were also measured for comparison. INTERVENTION: Speech perception was studied at
      50 and 65 dB SPL input levels in quiet and also in noise at levels of 65, 85, and
      100 dB SPL with SNRs of +6, +3, and -3 dB. This was done for all participants (HI
      and NH). In addition, the HI participants compared subjective preference between
      the aided and unaided presentations of speech and music stimuli at 50, 65, 85,
      and 100 dB SPL in quiet. DATA COLLECTION AND ANALYSIS: The data were analyzed
      with repeated-measures analysis of variance. RESULTS: The results showed a
      decrease in aided benefits as input levels increased. However, even at the two
      highest input levels (i.e., 85 and 100 dB SPL), aided speech scores were still
      higher than the unaided speech scores. Furthermore, NH listeners and HI listeners
      in the aided condition showed stable speech-in-noise performance between 65 and
      100 dB SPL input levels, except that the absolute performance of the NH listeners
      was higher than that of the HI listeners. Subjective preference for the unaided
      sounds versus the aided sounds increased as input level increased, with a
      crossover intensity at approximately 75 dB SPL for speech and 80 dB SPL for
      music. CONCLUSIONS: The results supported the hypothesis that the study hearing
      aid can provide aided speech-in-noise benefit at very high noise inputs in a
      controlled environment.

PMID- 25751696
TI  - Availability of binaural cues for pediatric bilateral cochlear implant
      recipients.
AB  - BACKGROUND: Bilateral implant recipients theoretically have access to binaural
      cues. Research in postlingually deafened adults with cochlear implants (CIs)
      indicates minimal evidence for true binaural hearing. Congenitally deafened
      children who experience spatial hearing with bilateral CIs, however, might
      perceive binaural cues in the CI signal differently. There is limited research
      examining binaural hearing in children with CIs, and the few published studies
      are limited by the use of unrealistic speech stimuli and background noise.
      PURPOSE: The purposes of this study were to (1) replicate our previous study of
      binaural hearing in postlingually deafened adults with AzBio sentences in
      prelingually deafened children with the pediatric version of the AzBio sentences,
      and (2) replicate previous studies of binaural hearing in children with CIs using
      more open-set sentences and more realistic background noise (i.e., multitalker
      babble). RESEARCH DESIGN: The study was a within-participant, repeated-measures
      design. STUDY SAMPLE: The study sample consisted of 14 children with bilateral
      CIs with at least 25 mo of listening experience. DATA COLLECTION AND ANALYSIS:
      Speech recognition was assessed using sentences presented in multitalker babble
      at a fixed signal-to-noise ratio. Test conditions included speech at 0 degrees 
      with noise presented at 0 degrees  (S0N0), on the side of the first CI (90
      degrees  or 270 degrees ) (S0N1stCI), and on the side of the second CI (S0N2ndCI)
      as well as speech presented at 0 degrees  with noise presented semidiffusely from
      eight speakers at 45 degrees  intervals. Estimates of summation, head shadow,
      squelch, and spatial release from masking were calculated. RESULTS: Results of
      test conditions commonly reported in the literature (S0N0, S0N1stCI, S0N2ndCI)
      are consistent with results from previous research in adults and children with
      bilateral CIs, showing minimal summation and squelch but typical head shadow and
      spatial release from masking. However, bilateral benefit over the better CI with
      speech at 0 degrees  was much larger with semidiffuse noise. CONCLUSIONS:
      Congenitally deafened children with CIs have similar availability of binaural
      hearing cues to postlingually deafened adults with CIs within the same
      experimental design. It is possible that the use of realistic listening
      environments, such as semidiffuse background noise as in Experiment II, would
      reveal greater binaural hearing benefit for bilateral CI recipients. Future
      research is needed to determine whether (1) availability of binaural cues for
      children correlates with interaural time and level differences, (2) different
      listening environments are more sensitive to binaural hearing benefits, and (3)
      differences exist between pediatric bilateral recipients receiving implants in
      the same or sequential surgeries.

PMID- 25751697
TI  - Reliability in Hearing Threshold Prediction in Normal-Hearing and Hearing
      Impaired Participants Using Mixed Multiple ASSR.
AB  - BACKGROUND AND PURPOSE: The rapidly evolving field of hearing aid fitting in
      infants requires rapid, objective, and highly reliable methods for diagnosing
      hearing impairment. The aim was to determine test-retest reliability in hearing
      thresholds predicted by multiple auditory steady-state response (ASSRthr) among
      normal-hearing (NH) and hearing-impaired (HI) adults, and to study differences
      between ASSRthr and pure-tone threshold (PTT) as a function of frequency in each
      participant. ASSR amplitude versus stimulus level was analyzed to study ASSR
      growth rate in NH and HI participants, especially at ASSRthr. RESEARCH DESIGN AND
      STUDY SAMPLE: Mixed multiple ASSR (100% AM, 20% FM), using long-time averaging at
      a wide range of stimulus levels, and PTT were recorded in 10 NH and 14 HI adults.
      ASSRthr was obtained in 10 dB steps simultaneously in both ears using a test
      retest protocol (center frequencies = 500, 1000, 2000, and 4000 Hz; modulation
      frequencies = 80-96 Hz). The growth rate at ASSRthr was calculated as the slope
      (nV/dB) of the ASSR amplitudes obtained at, and 10 dB above, ASSRthr. PTT was
      obtained in both ears in 1 dB steps using a fixed-frequency Bekesy technique. All
      of the NH participants showed PTTs better than 20 dB HL (125-8000 Hz), and mean
      pure-tone average (PTA; 500-4000 Hz) was 1.8 dB HL. The HI participants exhibited
      quite symmetrical sensorineural hearing losses, as revealed by a mean interaural
      PTA difference of 6.5 dB. Their mean PTA in the better ear was 38.7 dB HL.
      RESULTS: High ASSRthr reproducibility (independent of PTT) was found in both NH
      and HI participants (test-retest interquartile range = 10 dB). The prediction
      error was numerically higher in NH participants (f >=1000 Hz), although only a
      significant difference existed at 1000 Hz. The median difference between ASSRthr
      (dB HL) and PTT (dB HL) was approximately 10 dB in the HI group at frequencies of
      1000 Hz or greater, and 20 dB at 500 Hz. In general, the prediction error
      decreased (p < 0.001) with increasing hearing threshold, although large
      intersubject variability existed. Regression analysis (PTT versus ASSRthr) in HI
      participants revealed correlation coefficients between 0.72-0.88 (500-4000 Hz)
      and slopes at approximately 1.0. Large variability in ASSRthr-PTT versus
      frequency was demonstrated across HI participants (interquartile range
      approximately 20 dB). The maximum across-frequency difference (ASSRthr-PTT) in an
      individual participant was 50 dB. HI participants showed overall significantly
      higher amplitudes and slopes at ASSRthr than did NH participants (p < 0.02). The
      amplitude-intensity function revealed monotonically increasing ASSRs in NH
      participants (slope 2 nV/dB), whereas HI participants exhibited heterogeneous and
      mostly nonmonotonically increasing ASSRs. CONCLUSIONS: Long-time averaging of
      ASSR revealed high ASSRthr reproducibility and systematic decrease in prediction
      error with increasing hearing threshold, albeit large intersubject variability in
      prediction error existed. A plausible explanation for the systematic difference
      in ASSRthr between NH and HI adults might be significantly higher ASSR amplitudes
      and higher overall growth rates at ASSRthr among HI participants. Across
      frequency comparison of PTT and ASSRthr in an individual HI participant
      demonstrated large variation; thus, ASSR may not be optimal for, e.g., reliable
      threshold prediction in infants and subsequent fine-tuning of hearing aids.

PMID- 25751698
TI  - Efficacy of carnitine in treatment of tinnitus: evidence from audiological and
      MRI measures-a case study.
AB  - BACKGROUND: Tinnitus, or ringing in the ears, is an extremely common ear
      disorder. However, it is a phenomenon that is very poorly understood and has
      limited treatment options. PURPOSE: The goals of this case study were to identify
      if the antioxidant acetyl-L-carnitine (ALCAR) provides relief from tinnitus, and
      to identify if subjective satisfaction after carnitine treatment is accompanied
      by changes in audiological and imaging measures. RESEARCH DESIGN: Case Study.
      PATIENT CASE: A 41-yr-old female with a history of hearing loss and tinnitus was
      interested in exploring the benefits of antioxidant therapy in reducing her
      tinnitus. The patient was evaluated using a standard audiological/tinnitus test
      battery and magnetic resonance imaging (MRI) recordings before carnitine
      treatment. After her physician's approval, the patient took 500 mg of ALCAR twice
      a day for 30 consecutive days. The audiological and MRI measures were repeated
      after ALCAR treatment. DATA COLLECTION AND ANALYSIS: Pure-tone audiometry,
      tympanometry, distortion-product otoacoustic emissions, tinnitus questionnaires
      (Tinnitus Handicap Inventory and Tinnitus Reaction Questionnaire), auditory
      brainstem response, functional MRI (fMRI), functional connectivity MRI, and
      cerebral blood flow evaluations were conducted before intake of ALCAR and were
      repeated 30 days after ALCAR treatment. RESULTS: The patient's pretreatment pure
      tone audiogram indicated a mild sensorineural hearing loss at 6 kHz in the right
      ear and 4 kHz in the left ear. Posttreatment evaluation indicated marginal
      improvement in the patient's pure-tone thresholds, but was sufficient to be
      classified as being clinically normal in both ears. Distortion-product
      otoacoustic emissions results showed increased overall emissions after ALCAR
      treatment. Subjective report from the patient indicated that her tinnitus was
      less annoying and barely noticeable during the day after treatment, and the
      posttreatment tinnitus questionnaire scores supported her statement. Auditory
      brainstem response peak V amplitude growth between stimulus intensity levels of
      40-80 dB nHL indicated a reduction in growth for the posttreatment condition
      compared with the pretreatment condition. This was attributed to a possible
      active gating mechanism involving the auditory brainstem after ALCAR treatment.
      Posttreatment fMRI recordings in response to acoustic stimuli indicated a
      statistically significant reduction in brain activity in several regions of the
      brain, including the auditory cortex. Cerebral blood flow showed increased flow
      in the auditory cortex after treatment. The functional connectivity MRI indicated
      increased connectivity between the right and left auditory cortex, but a decrease
      in connectivity between the auditory cortex and some regions of the "default mode
      network," namely the medial prefrontal cortex and posterior cingulate cortex.
      CONCLUSIONS: The changes observed in the objective and subjective test measures
      after ALCAR treatment, along with the patient's personal observations, indicate
      that carnitine intake may be a valuable pharmacological option in the treatment
      of tinnitus.

PMID- 25751700
TI  - On-label and off-label use of high-dose influenza vaccine in the United States,
      2010-2012.
AB  - High-dose inactivated, influenza vaccine was licensed by the FDA in December 2009
      for adults aged 65 y and older. The ACIP did not issue or state a preference for
      a specific vaccine in the elderly population. The extent of its on-label and off
      label use is unknown. Using the MarketScan Commercial Claims and Encounters and
      the Medicare Supplemental database, we identified individuals who received the
      high-dose influenza vaccine or the standard, seasonal trivalent influenza vaccine
      between January 1, 2010 and December 31, 2012. For people aged >=65 y, we used
      multivariable regression to assess the association between patient and provider
      level variables and high-dose influenza vaccine versus standard influenza
      vaccine. We characterized all off-label high-dose vaccine administered to people
      younger than 65 y of age, and investigated whether sicker patients were targeted
      for off-label use by examining the association between various comorbid
      conditions and receipt of the high-dose vaccine among adults aged 18-64. Among
      patients aged >=65 y who received an influenza vaccine, 18.4% received the high
      dose vaccine. Uptake was minimal in 2010, but 25% and 32% of influenza shots were
      the high-dose formulation in 2011 and 2012, respectively. Almost 27,000 seniors
      received a second high-dose vaccine with a median of 368 d (IQR: 350-387 days)
      between doses. Older age, family practice physicians, and having PPO insurance
      were positively associated with receiving high-dose vaccine. There were 36,624
      off-label high-dose vaccines administered. Half of the patients receiving off
      label doses were aged 50-64. Adults aged 18-64 y receiving high-dose vaccine were
      more likely to have chronic comorbidities than people receiving standard
      influenza vaccine; however, there was not one specific illness that seemed to be
      targeted by physicians. In the first 3 y since licensure, use of the high-dose
      vaccine among seniors has been limited. The safety of this vaccine should be
      monitored closely among 2 groups of people - seniors receiving repeat doses and
      people <65.

PMID- 25751702
TI  - Band gap narrowing in nitrogen-doped La2Ti2O7 predicted by density-functional
      theory calculations.
AB  - In order to reveal the origin of enhanced photocatalytic activity of N-doped
      La2Ti2O7 in both the visible light and ultraviolet light regions, its electronic
      structure has been studied using spin-polarized conventional density functional
      theory (DFT) and the Heyd-Scuseria-Ernzerhof (HSE06) hybrid approach. The results
      show that the deep localized states are formed in the forbidden band when
      nitrogen solely substitutes for oxygen. Introducing the interstitial Ti atom into
      the N-doped La2Ti2O7 photocatalyst still causes the formation of a localized
      energy state. Two nitrogen substitutions co-exist stably with one oxygen vacancy,
      creating a continuum energy band just above the valence band maximum. The
      formation of a continuum band instead of mid-gap states can extend the light
      absorption to the visible light region without increasing the charge
      recombination, explaining the enhanced visible light performance without
      deteriorating the ultraviolet light photocatalytic activity. 

PMID- 25751701
TI  - Evaluation of Stepped Care for Chronic Pain (ESCAPE) in Veterans of the Iraq and
      Afghanistan Conflicts: A Randomized Clinical Trial.
AB  - IMPORTANCE: Despite the prevalence and the functional, psychological, and
      economic impact of chronic pain, few intervention studies of treatment of chronic
      pain in veterans have been performed. OBJECTIVE: To determine whether a stepped
      care intervention is more effective than usual care, as hypothesized, in reducing
      pain-related disability, pain interference, and pain severity. DESIGN, SETTING,
      AND PARTICIPANTS: We performed a randomized clinical trial comparing stepped care
      with usual care for chronic pain. We enrolled 241 veterans from Operation
      Enduring Freedom, Operation Iraqi Freedom, and Operation New Dawn with chronic
      (>3 months) and disabling (Roland Morris Disability Scale score, >=7)
      musculoskeletal pain of the cervical or lumbar spine or extremities (shoulders,
      knees, and hips) in the Evaluation of Stepped Care for Chronic Pain (ESCAPE)
      trial from December 20, 2007, through June 30, 2011. The 9-month follow-up was
      completed by April 2012. Patients received treatment at a postdeployment clinic
      and 5 general medicine clinics at a Veterans Affairs medical center.
      INTERVENTIONS: Step 1 included 12 weeks of analgesic treatment and optimization
      according to an algorithm coupled with pain self-management strategies; step 2,
      12 weeks of cognitive behavioral therapy. All intervention aspects were delivered
      by nurse care managers. MAIN OUTCOMES AND MEASURES: Pain-related disability
      (Roland Morris Disability Scale), pain interference (Brief Pain Inventory), and
      pain severity (Graded Chronic Pain Scale). RESULTS: The primary analysis included
      121 patients receiving the stepped-care intervention and 120 patients receiving
      usual care. At 9 months, the mean decrease from baseline in the Roland Morris
      Disability Scale score was 1.7 (95% CI, -2.6 to -0.9) points in the usual care
      group and 3.7 (95% CI, -4.5 to -2.8) points in the intervention group (between
      group difference, -1.9 [95% CI, -3.2 to -0.7] points; P=.002). The mean decrease
      from baseline in the Pain Interference subscale score of the Brief Pain Inventory
      was 0.9 points in the usual care group and 1.7 points in the intervention group
      (between-group difference, -0.8 [95% CI, -1.3 to -0.3] points; P=.003). The
      Graded Chronic Pain Scale severity score was reduced by 4.5 points in the usual
      care group and 11.1 points in the intervention group (between-group difference, 
      6.6 [95% CI, -10.5 to -2.7] points; P=.001). CONCLUSIONS AND RELEVANCE: A stepped
      care intervention that combined analgesics, self-management strategies, and brief
      cognitive behavioral therapy resulted in statistically significant reductions in
      pain-related disability, pain interference, and pain severity in veterans with
      chronic musculoskeletal pain. TRIAL REGISTRATION: clinicaltrials.gov Identifier:
      NCT00386243.

PMID- 25751703
TI  - Breaking the addictive cycle of the system: improving US criminal justice
      practices to address substance use disorders.
AB  - PURPOSE: Recent political commentary in the USA has suggested that there is great
      potential for current criminal justice practices designed for drug-involved
      offenders to be significantly overhauled in the near future. It is imperative to
      plan for these changes by assessing how well current programs serve drug-involved
      criminal justice populations. The paper aims to discuss these issues.
      DESIGN/METHODOLOGY/APPROACH: This critical assessment begins with an overview of
      the most recent research on the prevalence and impact that substance use
      disorders have within the criminal justice system. Although the evidence
      demonstrates that relying on incarceration as a crime control method for drug
      involved offenders has many shortcomings, there are innovative new programs being
      adopted across the country. Two of these promising programs are discussed, as
      well as the potential results that could be realized from integrating medication
      assisted treatment into appropriate criminal justice programs designed for drug
      involved offenders. FINDINGS: Incarceration is a failed practice for attending to
      the underlying reasons why many drug-involved offenders become involved in
      criminal activities. There are encouraging new programs emerging in different
      parts of the USA, but the inclusion of supplemental treatment options could
      further promote positive outcomes. ORIGINALITY/VALUE: The impending expansion of
      criminal justice programs for drug-involved offenders must consider how
      innovative new programs can be fused with supplemental treatment options to
      achieve the best results.

PMID- 25751704
TI  - Injecting drug use in prison: prevalence and implications for needle exchange
      policy.
AB  - PURPOSE: The purpose of this paper is to explore prison drug injecting
      prevalence, identify any changes in injecting prevalence and practice during
      imprisonment and explore views on prison needle exchange.
      DESIGN/METHODOLOGY/APPROACH: An empirical prospective cohort survey conducted
      between 2006 and 2008. The study involved a random sample of 267 remand and
      sentenced prisoners from a large male category B prison in England where no
      prison needle exchange operates. Questionnaires were administered with prisoners
      on reception and, where possible, at one, three and six months during their
      sentence. FINDINGS: In total, 64 per cent were injecting until admission into
      prison. The majority intended to stop injecting in prison (93 per cent), almost a
      quarter due to the lack of needle exchange (23 per cent). Yet when hypothetically
      asked if they would continue injecting in prison if needle exchange was freely
      available, a third of participants (33 per cent) believed that they would.
      Injecting cessation happened on prison entry and appeared to be maintained during
      the sentence. RESEARCH LIMITATIONS/IMPLICATIONS: Not providing sterile needles
      may increase risks associated with injecting for prisoners who continue to
      inject. However, providing such equipment may prolong injecting for other
      prisoners who currently cease injecting on account of needle exchange programmes
      (NEPs) not being provided in the UK prison setting. Practical implications - Not
      providing sterile needles may increase risks associated with injecting for
      prisoners who continue to inject. However, providing such equipment may prolong
      injecting for other prisoners who currently cease injecting on account of NEPs
      not being provided in the UK prison setting. ORIGINALITY/VALUE: This survey is
      the first to question specifically regarding the timing of injecting cessation
      amongst male prisoners and explore alongside intention to inject should needle
      exchange facilities be provided in prison.

PMID- 25751705
TI  - Drug and alcohol use and treatment for Australian Indigenous and non-Indigenous
      prisoners: demand reduction strategies.
AB  - PURPOSE: The purpose of this paper is to compare the use of drugs and alcohol by
      Indigenous and non-Indigenous prisoners and examine relevant treatment in
      Australian prisons. DESIGN/METHODOLOGY/APPROACH: Prison authorities were surveyed
      about alcohol and drug use by prisoners prior to and during imprisonment and drug
      and alcohol treatment programs in prison. The literature was review for
      information on alcohol and drug use and treatment in Australian prisons.
      FINDINGS: In 2009, over 80 percent of Indigenous and non-Indigenous inmates
      smoked. Prior to imprisonment, many Indigenous and non-Indigenous inmates drank
      alcohol at risky levels (65 vs 47 percent) and used illicit drugs (over 70
      percent for both groups). Reports of using heroin (15 vs 21 percent), ATS (21 vs
      33 percent), cannabis (59 vs 50 percent) and injecting (61 vs 53 percent) were
      similarly high for both groups. Prison-based programs included detoxification,
      Opioid Substitution Treatment, counselling and drug free units, but access was
      limited especially among Indigenous prisoners. RESEARCH LIMITATIONS/IMPLICATIONS:
      Drug and alcohol use was a significant issue in Australian prisons. Prisoners
      were over five times more likely than the general population to have a substance
      use disorder. Imprisonment provides an important opportunity for rehabilitation
      for offenders. This opportunity is especially relevant to Indigenous prisoners
      who were more likely to use health services when in prison than in the community
      and given their vast over representations in prison populations. PRACTICAL
      IMPLICATIONS: Given the effectiveness of treatment in reducing re-offending
      rates, it is important to expand drug treatment and especially culturally
      appropriate treatment programs for Indigenous inmates. ORIGINALITY/VALUE: Very
      little is known about Indigenous specific drug and alcohol programs in Australian
      prisons.

PMID- 25751706
TI  - Smoking cessation in male prisoners: a literature review.
AB  - PURPOSE: The purpose of this paper is to review the available literature relating
      to smoking cessation (SC) for the male prisoner population.
      DESIGN/METHODOLOGY/APPROACH: Databases PubMed, CINAHL and MEDLINE were searched
      for English language studies from 1990 to 2012. The authors identified 12 papers
      examining SC in male prisoners. Full-text articles were analysed for inclusion.
      FINDINGS: A total of 12 studies were identified for inclusion. Four studies
      focused on forced abstinence (a smoking ban) while the remainder looked at
      various combinations of nicotine replacement, pharmacology and behavioural
      techniques. No robust studies were found that examined nursing approaches to SC
      for the prisoner population. The evidence shows a strong "pro-smoking" culture in
      prison and that many prisoners continue to smoke irrespective of an enforced ban.
      However, SC strategies can be successful if implemented systematically and
      supported by consistent policies. RESEARCH LIMITATIONS/IMPLICATIONS: Female-only
      prisoner studies were excluded as females comprise just 7 per cent of the
      Australian prisoner population. The analysis does not differentiate between
      maximum- or minimum-security prisons, or length of prison sentence. Results
      cannot be generalised to other forms of detention such as police custody or
      immigration detention centres. Studies were not appraised for quality, as
      exclusion on that basis would render further exploration untenable. The analysis
      was presented in a narrative rather than meta-analytical format and may be
      subject to interpretation. PRACTICAL IMPLICATIONS: This paper provides a
      foundation on which to build further research evidence into the smoking behaviour
      of prisoners. This information can be used to advocate for healthier public
      policy for a vulnerable and marginalised population. ORIGINALITY/VALUE: To the
      authors' knowledge, this is the first literature review into SC interventions in
      prisons. The authors apply the findings of this literature review to the five
      strategies for health promotion to propose a population approach to smoking
      cessation in male prisoners. Recommendations specific to the correctional
      environment are outlined for consideration by correctional health professionals.

PMID- 25751707
TI  - Incarcerated women's HPV awareness, beliefs, and experiences.
AB  - PURPOSE: The purpose of this paper is to explore incarcerated women's awareness,
      beliefs, and experiences with human papillomavirus (HPV) infection and
      vaccination. DESIGN/METHODOLOGY/APPROACH: Researchers conducted focus groups with
      45 incarcerated women in an urban Midwestern US jail to assess how women talked
      about their Papanicolaou (Pap) test screening and abnormal Pap test follow-up
      experiences. Some focus group questions specifically assessed individual
      awareness, beliefs, and experiences with HPV infection and vaccination. Based on
      these data, the authors described participants' awareness of HPV, as well as used
      open coding to ultimately extract themes related to beliefs and experiences with
      HPV infection and vaccine. FINDINGS: While all 45 participants reported
      experiencing an abnormal Pap test event within the last five years, only two
      thirds of participants (n=30) reported having heard of the HPV infection. Several
      themes emerged from the analysis of the data: the women's beliefs about cause and
      severity of HPV; frustration with age requirements of the vaccine; varied
      experiences with vaccinations for themselves and their children; the impact of
      media exposure on knowledge; and desire for more HPV infection and vaccine
      information. ORIGINALITY/VALUE: Incarcerated women's awareness and limited
      experiences with HPV infection and vaccination may be a barrier to adequate
      screening and cervical cancer prevention. This study has implications for the
      development of cervical health education for this high-risk group of women, who
      are four to five times as likely to have cervical cancer as non-incarcerated
      women.

PMID- 25751708
TI  - Aging, Depression, and Wisdom: A Pilot Study of Life-Review Intervention and PTSD
      Treatment With Two Groups of Vietnam Veterans.
AB  - Vietnam War veterans are a sometimes overlooked subgroup of the aging baby boomer
      generation. Forty years after the war ended, war veterans still seek out VA or
      Vet Center counselors to assist with traumatic stress symptoms. However, there
      currently are no specific age-related protocols for treating older war veterans
      suffering from posttraumatic stress disorder (PTSD), nor have established PTSD
      interventions incorporated gerontology content for these older trauma survivors.
      This pilot study juxtaposed life review within regular PTSD group counseling for
      12 Vietnam veterans at a community-based Vet Center using a partial crossover
      design. The Life Review and Experiencing Form (LREF) structured the delivery of
      the life review component. T-tests and repeated measures ANOVA were used to
      examine depression and self-assessed wisdom outcomes using measures previously
      tested with older adults. Findings suggest that life review prior to PTSD group
      therapy has clinical benefits for reducing symptoms of depression and increasing
      self-assessed wisdom. The study illuminates the possible relationship of
      traumatic stress symptom effects on the natural reminiscing process for older
      veterans and provides insights into methods for more age-appropriate treatment
      for trauma survivors participating in Vet Center and VA programs nationwide. 

PMID- 25751710
TI  - Iron catalysis in organic synthesis.

PMID- 25751709
TI  - Stigmatizing attitudes and beliefs toward bulimia nervosa: the importance of
      knowledge and eating disorder symptoms.
AB  - Widely held stigmatizing attitudes and beliefs toward bulimic eating disorders
      may lead to self-blame and reduced treatment seeking. Knowledge and familiarity
      with mental disorders may help decrease associated stigma. However, these
      relationships are not well understood in bulimia nervosa (BN). A community sample
      of 1828 adults aged 18 to 70 years completed a survey assessing stigmatizing
      attitudes and beliefs toward BN, knowledge and familiarity with the disorder, as
      well as levels of eating disorder symptoms. Knowledge of BN was negatively
      associated with three dimensions of stigmatization, personal responsibility (rho
      = -0.28), unreliability (rho = -0.19), and advantages of BN (rho = -0.23).
      Familiarity revealed no association with stigmatization. Both men and women with
      high levels of eating disorder symptoms perceived BN as less serious than the
      participants with low levels of symptoms. Increasing community knowledge about
      bulimia may help mitigate stigmatization and perceived barriers to treatment. 

PMID- 25751711
TI  - Eating disorders and psychopathological traits in obese preadolescents and
      adolescents.
AB  - OBJECTIVE: to investigate the presence of eating disorders (ED) and
      psychopathological traits in obese preadolescents and adolescents compared to
      normal-weight peers. DESIGN: Overweight/obese patients aged 11 to 14 y and normal
      weight peers' data collected by means of self-report questionnaires administered
      to parents and children. SETTING: Clinical Nutrition Units in the Municipalities
      of Rome, Naples, Gallipoli and Atri, Italy. SUBJECTS: 376 preadolescents and
      adolescents. Patients were 187 (93 boys, BMI=27.9+/-;4.1; 94 girls, BMI=28.1+/
      4.5); normal-weight controls were 189 subjects (94 boys, BMI=19.4+/-1.4; 95
      girls, BMI=19.5+/-1.5). MEASURES OF OUTCOME: eating disorder behaviors,
      psychopathological traits and symptoms estimated by means of the eating disorders
      scales (EDI-2) and psychopathological scales (CBCL 4-18). RESULTS: Patients
      reached higher scores than controls in most of the eating disorders scales and
      psychopathological scales. Twenty-one (11.2%) patients were considered at risk of
      developing an eating disorder and 75 (40%) presented social problems. With regard
      to weight status, age-group and gender, main significant interaction effects were
      seen in social problems (F= 6.50; p<0.05) and ineffectiveness (F= 4.15; p<0.05).
      CONCLUSIONS: Findings from our study demonstrate that in preadolescence and
      adolescence, obesity is significantly associated to some traits typical of ED and
      to psychological problems in general. Although no inference can be made with
      regard to direction of causality, it is possible to conclude that overweight
      preadolescents and adolescents can be prone to display problematic traits more
      commonly associated to eating disorders and to present a high degree of mental
      distress.

PMID- 25751712
TI  - Longitudinal Correlates of Sluggish Cognitive Tempo and ADHD-Inattention Symptom
      Dimensions with Spanish Children.
AB  - The objective was to examine the longitudinal correlates of sluggish cognitive
      tempo (SCT) and attention deficit/hyperactivity disorder (ADHD)-Inattention (IN)
      dimensions with mothers' and fathers' ratings of Spanish children. Mothers and
      fathers rated SCT, ADHD-IN, ADHD-hyperactivity/impulsivity (HI), oppositional
      defiant disorder (ODD), depression, academic impairment, and social impairment on
      3 occasions (twice in first-grade year [6-week separation] and once in the second
      grade year [12 months after the first assessment]) in Spanish children (758, 746,
      and 718 children at the 3 time-points with approximately 55% boys). The results
      showed that (a) higher levels of SCT from earlier assessments predicted higher
      levels of depression, academic impairment, and social impairment at Assessment 3
      after controlling for ADHD-IN at earlier assessments; (b) higher levels of ADHD
      IN from earlier assessments predicted higher levels of depression, academic
      impairment, and social impairment at Assessment 3 after controlling for SCT at
      earlier assessments; (c) higher levels of ADHD-IN from earlier assessments
      predicted higher levels of ADHD-HI and ODD at Assessment 3 after controlling for
      SCT from earlier assessments; and (d) higher levels of SCT from earlier
      assessments either showed no unique relationship with ADHD-HI and ODD or
      predicted lower levels of ADHD-HI and ODD at Assessment 3 after controlling for
      ADHD-IN from earlier assessments. Initial evidence is provided of SCT's unique
      longitudinal relationships with depression and academic/social impairment and
      different longitudinal relationships with ADHD-HI and ODD relative to ADHD-IN,
      thus adding to a growing body of research underscoring the importance of SCT as
      distinct from ADHD-IN.

PMID- 25751713
TI  - Highly efficient forward osmosis based on porous membranes--applications and
      implications.
AB  - For the first time, forward osmosis (FO) was performed using a porous membrane
      with an ultrafiltration (UF)-like rejection layer and its feasibility for high
      performance FO filtration was demonstrated. Compared to traditional FO membranes
      with dense rejection layers, the UF-like FO membrane was 2 orders of magnitude
      more permeable. This gave rise to respectable FO water flux even at ultralow
      osmotic driving force, for example, 7.6 L/m(2).h at an osmotic pressure of merely
      0.11 bar (achieved by using a 0.1% poly(sodium 4-styrene-sulfonate) draw
      solution). The membrane was applied to oil/water separation, and a highly stable
      FO water flux was achieved. The adoption of porous FO membranes opens a door to
      many new opportunities, with potential applications ranging from wastewater
      treatment, valuable product recovery, and biomedical applications. The potential
      applications and implications of porous FO membranes are addressed in this paper.

PMID- 25751714
TI  - Real-time observation of ultrafast electron injection at graphene-Zn porphyrin
      interfaces.
AB  - We report on the ultrafast interfacial electron transfer (ET) between zinc(II)
      porphyrin (ZnTMPyP) and negatively charged graphene carboxylate (GC) using state
      of-the-art femtosecond laser spectroscopy with broadband capabilities. The steady
      state interaction between GC and ZnTMPyP results in a red-shifted absorption
      spectrum, providing a clear indication for the binding affinity between ZnTMPyP
      and GC via electrostatic and pi-pi stacking interactions. Ultrafast transient
      absorption (TA) spectra in the absence and presence of three different GC
      concentrations reveal (i) the ultrafast formation of singlet excited ZnTMPyP*,
      which partially relaxes into a long-lived triplet state, and (ii) ET from the
      singlet excited ZnTMPyP* to GC, forming ZnTMPyP(+) and GC(-), as indicated by a
      spectral feature at 650-750 nm, which is attributed to a ZnTMPyP radical cation
      resulting from the ET process.

PMID- 25751715
TI  - (Too) optimistic about optimism: the belief that optimism improves performance.
AB  - A series of experiments investigated why people value optimism and whether they
      are right to do so. In Experiments 1A and 1B, participants prescribed more
      optimism for someone implementing decisions than for someone deliberating,
      indicating that people prescribe optimism selectively, when it can affect
      performance. Furthermore, participants believed optimism improved outcomes when a
      person's actions had considerable, rather than little, influence over the outcome
      (Experiment 2). Experiments 3 and 4 tested the accuracy of this belief; optimism
      improved persistence, but it did not improve performance as much as participants
      expected. Experiments 5A and 5B found that participants overestimated the
      relationship between optimism and performance even when their focus was not on
      optimism exclusively. In summary, people prescribe optimism when they believe it
      has the opportunity to improve the chance of success-unfortunately, people may be
      overly optimistic about just how much optimism can do.

PMID- 25751716
TI  - Procedural frames in negotiations: how offering my resources versus requesting
      yours impacts perception, behavior, and outcomes.
AB  - Although abundant negotiation research has examined outcome frames, little is
      known about the procedural framing of negotiation proposals (i.e., offering my
      vs. requesting your resources). In a series of 8 experiments, we tested the
      prediction that negotiators would show a stronger concession aversion and attain
      better individual outcomes when their own resource, rather than the
      counterpart's, is the accentuated reference resource in a transaction. First,
      senders of proposals revealed a stronger concession aversion when they offered
      their own rather than requested the counterpart's resources-both in buyer-seller
      (Experiment 1a) and in classic transaction negotiations (Experiment 2a).
      Expectedly, this effect reversed for recipients: When receiving requests rather
      than offers, recipients experienced a stronger concession aversion in buyer
      seller (Experiment 1b) and transaction negotiations (Experiment 2b). Experiments
      3-5 investigated procedural frames in the interactive process of negotiations
      with elementary schoolchildren (Experiment 3), in a buyer-seller context
      (Experiments 4a and 4b), and in a computer-mediated transaction negotiation void
      of buyer and seller roles (Experiment 5). In summary, 8 experiments showed that
      negotiators are more concession averse and claim more individual value when
      negotiation proposals are framed to highlight their own rather than the
      counterpart's resources.

PMID- 25751717
TI  - "All or nothing": attachment avoidance and the curvilinear effects of partner
      support.
AB  - People high in attachment avoidance typically respond more negatively to partner
      support, but some research suggests they can be calmed by high levels of
      practical support. In the present research, we attempted to reconcile these
      inconsistencies by modeling curvilinear associations between romantic partners'
      support and support recipients' outcomes and testing whether these curvilinear
      associations were moderated by recipients' degree of attachment avoidance. We
      examined the effect of partner support during support-relevant discussions
      (Studies 1-3) and in daily life (Study 4) on support recipients' distress
      (Studies 1-4), self-efficacy (Studies 2 and 3), perceived partner
      control/criticism (Studies 2 and 4), and distancing from the partner (Study 4).
      The results and a meta-analysis across all four studies (N = 298 couples)
      demonstrated that the curvilinear effect of practical support on recipients'
      outcomes was moderated by attachment avoidance. Highly avoidant recipients
      exhibited more negative responses as their partner provided them low-to-moderate
      levels of practical support, including increasing distress, perceived partner
      control/criticism and distancing, and decreasing self-efficacy. However, as
      partners' practical support shifted from moderate to high levels, highly avoidant
      recipients experienced more positive outcomes, including decreasing distress,
      perceived partner control/criticism and distancing, and increasing self-efficacy.
      Less avoidant individuals were resilient and experienced better outcomes
      regardless of the level of partner support they received. These results
      demonstrate the utility of curvilinear models in reconciling the costs and
      benefits of support, and indicate that high levels of practical support can
      overcome the defenses of highly avoidant individuals by offering undeniable
      evidence of the partner's availability.

PMID- 25751718
TI  - Variation in narrative identity is associated with trajectories of mental health
      over several years.
AB  - This article presents 2 longitudinal studies designed to assess the relationship
      between variability in narrative identity and trajectories of mental health over
      several years. In Study 1, core scenes from 89 late-mid-life adults' life stories
      were assessed for several narrative themes. Participants' mental health and
      physical health were assessed concurrently with the narratives and annually for
      the subsequent 4 years. Concurrent analyses indicated that the themes of agency,
      redemption, and contamination were significantly associated with mental health.
      Longitudinal analyses indicated that these same 3 themes were significantly
      associated with participants' trajectories of mental health over the course of 4
      years. Exploratory analyses indicated that narratives of challenging experiences
      may be central to this pattern of results. In Study 2, similar longitudinal
      analyses were conducted on a sample of 27 late-mid-life adults who received a
      major physical illness diagnosis between the baseline assessment and 6 months
      later and a matched sample of 27 control participants who remained healthy
      throughout the study. Participants' mental health and physical health were
      assessed every 6 months for 2 years. In this study, the themes of agency,
      communion, redemption, and contamination in participants' life narratives
      collected at baseline (before any participant became sick) were significantly
      associated with mental health in the group of participants who went on to receive
      a medical diagnosis, but not in the control group. Taken together, the results of
      these 2 studies indicate that the way an individual constructs personal
      narratives may impact his or her trajectory of mental health over time.

PMID- 25751719
TI  - Correction to Masuda et al. (2008).

PMID- 25751720
TI  - Hormonal Contraception and Risk of Psychiatric and Other Noncommunicable Diseases
      in HIV-Infected Women.
AB  - BACKGROUND: Hormonal contraception use is common among human immunodeficiency
      virus (HIV)-infected women. Risk of psychiatric and other noninfectious
      complications of hormonal contraception use has not been described in this
      population. METHODS: We performed a retrospective cohort study of HIV-infected
      women receiving care in Tennessee from 1998 to 2008 to examine the risks of
      incident psychiatric and other noncommunicable diseases (NCDs), including
      cardiovascular, hepatic, renal, and malignant diseases, and hormonal
      contraception use, including depot medroxyprogesterone acetate (DMPA) and
      combined estrogen- and progestin-containing hormonal contraceptives. We used
      marginal structural models with inverse probability weights to account for time
      varying confounders associated with hormonal contraception use. RESULTS: Of the
      392 women included, 94 (24%) used hormonal contraception during the study period.
      Baseline psychiatric disease was similar between women who received and did not
      receive hormonal contraception. There were 69 incident psychiatric diagnoses and
      72 NCDs. Only time-varying DMPA use was associated with increased risk of
      psychiatric disease (adjusted odds ratio [aOR] 3.70; 95% confidence interval [95%
      CI] 1.32-10.4) and mood disorders, specifically (aOR 4.70 [1.87-11.8]). Time
      varying and cumulative combined hormonal contraception use were not statistically
      associated with other NCDs (aOR 1.64, 95% CI 0.64-4.12 and aOR 1.16, 95% CI 0.86
      1.56, respectively). However, risk of incident NCDs was increased with cumulative
      DMPA exposure (per year exposure aOR 1.45, 95% CI 1.01-2.08). CONCLUSIONS: Among
      HIV-infected women, DMPA was associated with risk of incident psychiatric
      diseases, particularly mood disorders, during periods of use. Cumulative DMPA
      exposure was also associated with risk of other NCDs. However, combined estrogen
      and progestin-containing hormonal contraception use was not statistically
      associated with risk of any NCDs.

PMID- 25751721
TI  - Methemoglobin is an endogenous toll-like receptor 4 ligand-relevance to
      subarachnoid hemorrhage.
AB  - Neuroinflammation is a well-recognized consequence of subarachnoid hemorrhage
      (SAH), and may be responsible for important complications of SAH. Signaling by
      Toll-like receptor 4 (TLR4)-mediated nuclear factor kappaB (NFkappaB) in
      microglia plays a critical role in neuronal damage after SAH. Three molecules
      derived from erythrocyte breakdown have been postulated to be endogenous TLR4
      ligands: methemoglobin (metHgb), heme and hemin. However, poor water solubility
      of heme and hemin, and lipopolysaccharide (LPS) contamination have confounded our
      understanding of these molecules as endogenous TLR4 ligands. We used a 5-step
      process to obtain highly purified LPS-free metHgb, as confirmed by Fourier
      Transform Ion Cyclotron Resonance mass spectrometry and by the Limulus amebocyte
      lysate assay. Using this preparation, we show that metHgb is a TLR4 ligand at
      physiologically relevant concentrations. metHgb caused time- and dose-dependent
      secretion of the proinflammatory cytokine, tumor necrosis factor alpha
      (TNFalpha), from microglial and macrophage cell lines, with secretion inhibited
      by siRNA directed against TLR4, by the TLR4-specific inhibitors, Rs-LPS and TAK
      242, and by anti-CD14 antibodies. Injection of purified LPS-free metHgb into the
      rat subarachnoid space induced microglial activation and TNFalpha upregulation.
      Together, our findings support the hypothesis that, following SAH, metHgb in the
      subarachnoid space can promote widespread TLR4-mediated neuroinflammation. 

PMID- 25751722
TI  - Identification and pharmacokinetics of multiple potential bioactive constituents
      after oral administration of radix astragali on cyclophosphamide-induced
      immunosuppression in Balb/c mice.
AB  - Radix Astragali (RA) is one of the commonly-used traditional Chinese medicines
      (TCMs) with an immunomodulatory effect confirmed in the clinic. In order to
      better understand the material basis for the therapeutic effects, this study was
      to investigate the absorbed components and their pharmacokinetic profile after
      oral administration of RA on cyclophosphamide-induced immunosuppression in Balb/c
      mice. As a result, 51 compounds in RA extract and 31 prototype compounds with
      nine metabolites were detected in mice plasma by the ultra-fast liquid
      chromatography (UFLC)-DAD-Q-TOF-MS/MS method. The pharmacokinetic parameters of
      five main constituents, including calycosin-7-O-glucoside, ononin, calycosin,
      formononetin and astragaloside IV, were obtained using HPLC-MS/MS. These results
      offered useful information for research on the pharmacological mechanism of RA
      and for its further development. 

PMID- 25751723
TI  - Correction: Xie, H.; et al. 3D QSAR studies, pharmacophore modeling and virtual
      screening on a series of steroidal aromatase inhibitors. Int. J. Mol. Sci. 2014,
      15, 20927-20947.
AB  - A number of sentences in the first paragraph of the introduction of [28] were
      copied verbatim from [21,22,25,29]. Although [21,22,25] were cited in the text,
      [29] was omitted and it was not made sufficiently clear that direct quotations
      were used. The authors wish to apologize to the authors of [21,22,25,29] and to
      the readers of the journal for any inconvenience.

PMID- 25751725
TI  - An epigenetic regulator: methyl-CpG-binding domain protein 1 (MBD1).
AB  - DNA methylation is an important form of epigenetic regulation in both normal
      development and cancer. Methyl-CpG-binding domain protein 1 (MBD1) is highly
      related to DNA methylation. Its MBD domain recognizes and binds to methylated
      CpGs. This binding allows it to trigger methylation of H3K9 and results in
      transcriptional repression. The CXXC3 domain of MBD1 makes it a unique member of
      the MBD family due to its affinity to unmethylated DNA. MBD1 acts as an
      epigenetic regulator via different mechanisms, such as the formation of the
      MCAF1/MBD1/SETDB1 complex or the MBD1-HDAC3 complex. As methylation status always
      changes along with carcinogenesis or neurogenesis, MBD1 with its interacting
      partners, including proteins and non-coding RNAs, participates in normal or
      pathological processes and functions in different regulatory systems. Because of
      the important role of MBD1 in epigenetic regulation, it is a good candidate as a
      therapeutic target for diseases. 

PMID- 25751726
TI  - The infection efficiency and replication ability of circularized HBV DNA
      optimized the linear HBV DNA in vitro and in vivo.
AB  - Studies on molecular mechanisms of the persist infection of hepatitis B virus
      have been hampered by a lack of a robust animal model. We successfully
      established a simple, versatile, and reproducible HBV persist infection model in
      vitro and in vivo with the circularized HBV DNA. The cells and mice were
      transfected or injected with circularized HBV DNA and pAAV/HBV1.2, respectively.
      At the indicated time, the cells, supernatants, serum samples, and liver tissues
      were collected for virological and serological detection. Both in vitro and in
      vivo, the circularized HBV DNA and pAAV/HBV1.2 could replicate and transcribe
      efficiently, but the infection effect of the former was superior to the latter (p
      < 0.05). The injection of circularized HBV genome DNA into the mice robustly
      supported HBV infection and approximately 80% of HBV infected mice established
      persistent infection for at least 10 weeks. This study demonstrated that the
      infection efficiency and replication ability of the circularized structure of HBV
      DNA overmatched that of the expression plasmid containing the linear structure of
      HBV DNA in vitro and in vivo. Meanwhile, this research results could provide
      useful tools and methodology for further study of pathogenic mechanisms and
      potential antiviral treatments of human chronic HBV infection in vitro and in
      vivo. 

PMID- 25751724
TI  - Ceramide-induced apoptosis in renal tubular cells: a role of mitochondria and
      sphingosine-1-phoshate.
AB  - Ceramide is synthesized upon stimuli, and induces apoptosis in renal tubular
      cells (RTCs). Sphingosine-1 phosphate (S1P) functions as a survival factor. Thus,
      the balance of ceramide/S1P determines ceramide-induced apoptosis. Mitochondria
      play a key role for ceramide-induced apoptosis by altered mitochondrial outer
      membrane permeability (MOMP). Ceramide enhances oligomerization of pro-apoptotic
      Bcl-2 family proteins, ceramide channel, and reduces anti-apoptotic Bcl-2
      proteins in the MOM. This process alters MOMP, resulting in generation of
      reactive oxygen species (ROS), cytochrome C release into the cytosol, caspase
      activation, and apoptosis. Ceramide regulates apoptosis through mitogen-activated
      protein kinases (MAPKs)-dependent and -independent pathways. Conversely, MAPKs
      alter ceramide generation by regulating the enzymes involving ceramide
      metabolism, affecting ceramide-induced apoptosis. Crosstalk between Bcl-2 family
      proteins, ROS, and many signaling pathways regulates ceramide-induced apoptosis.
      Growth factors rescue ceramide-induced apoptosis by regulating the enzymes
      involving ceramide metabolism, S1P, and signaling pathways including MAPKs. This
      article reviews evidence supporting a role of ceramide for apoptosis and
      discusses a role of mitochondria, including MOMP, Bcl-2 family proteins, ROS, and
      signaling pathways, and crosstalk between these factors in the regulation of
      ceramide-induced apoptosis of RTCs. A balancing role between ceramide and S1P and
      the strategy for preventing ceramide-induced apoptosis by growth factors are also
      discussed. 

PMID- 25751728
TI  - The Arabidopsis NAC transcription factor NST2 functions together with SND1 and
      NST1 to regulate secondary wall biosynthesis in fibers of inflorescence stems.
AB  - Transcriptional regulation of secondary wall biosynthesis in Arabidopsis thaliana
      has been shown to be mediated by a group of secondary wall NAC master switches,
      including NST1, NST2, SND1 and VND1 to VND7. It has been shown that VND1 to VND7
      regulate secondary wall biosynthesis in vessels, NST1 and NST2 function
      redundantly in anther endothecium, and SND1 and NST1 are required for secondary
      wall thickening in fibers of stems. However, it is unknown whether NST2 is
      involved in regulating secondary wall biosynthesis in fibers of stems. In this
      report, we demonstrated that similar to SND1, NST2 together with NST1 were highly
      expressed in interfascicular fibers and xylary fibers but not in vessels of
      stems. Although simultaneous mutations of SND1 and NST1 have been shown to result
      in a significant impairment of secondary wall thickening in fibers, a small
      amount of secondary walls was deposited in fibers during the late stage of stem
      development. In contrast, simultaneous mutations of SND1, NST1 and NST2 led to a
      complete loss of secondary wall thickening in fibers. These results demonstrate
      that NST2 together with SND1 and NST1 regulate secondary wall biosynthesis in
      fibers of stems. 

PMID- 25751729
TI  - Emerging Trends in Microwave Processing of Spices and Herbs.
AB  - Today, spices are integral part of our food as they provide sensory attributes
      such as aroma, color, flavour and taste to food. Further their antimicrobial,
      antioxidant, pharmaceutical and nutritional properties are also well known. Since
      spices are seasonal so their availability can be extended year round by adopting
      different preservation techniques. Drying and extraction are most important
      methods for preservation and value addition to spices. There are different
      techniques for drying of spices with their own advantages and limitations. A
      novel, non-conventional technique for drying of spices is use of microwave
      radiation. This technique proved to be very rapid, and also provide a good
      quality product. Similarly, there are a number of non-conventional extraction
      methods in use that are all, in principle, solid-liquid extractions but which
      introduce some form of additional energy to the process in order to facilitate
      the transfer of analytes from sample to solvent. This paper reviews latest
      advances in the use of microwave energy for drying of spices and herbs. Also, the
      review describes the potential application of microwave energy for extraction of
      essential oil/bioactive components from spices and herbs and the advantages of
      microwave-assisted process over the other extraction processes generally employed
      for extraction. It also showcases some recent research results on microwave
      drying/extraction from spices and herbs. 

PMID- 25751727
TI  - Potential epigenetic mechanism in non-alcoholic Fatty liver disease.
AB  - Non-alcoholic fatty liver disease (NAFLD) is characterized by excessive fat
      accumulation in the liver. It ranges from simple steatosis to its more aggressive
      form, non-alcoholic steatohepatitis (NASH), which may develop into hepatic
      fibrosis, cirrhosis, or hepatocellular carcinoma (HCC) if it persists for a long
      time. However, the exact pathogenesis of NAFLD and the related metabolic
      disorders remain unclear. Epigenetic changes are stable alterations that take
      place at the transcriptional level without altering the underlying DNA sequence.
      DNA methylation, histone modifications and microRNA are among the most common
      forms of epigenetic modification. Epigenetic alterations are involved in the
      regulation of hepatic lipid metabolism, insulin resistance, mitochondrial damage,
      oxidative stress response, and the release of inflammatory cytokines, all of
      which have been implicated in the development and progression of NAFLD. This
      review summarizes the current advances in the potential epigenetic mechanism of
      NAFLD. Elucidation of epigenetic factors may facilitate the identification of
      early diagnositic biomarkers and development of therapeutic strategies for NAFLD.

PMID- 25751730
TI  - Blue-emitting K2Al2B2O7:Eu(2+) phosphor with high thermal stability and high
      color purity for near-UV-pumped white light-emitting diodes.
AB  - Novel blue-emitting K2Al2B2O7:Eu(2+) (KAB:Eu(2+)) phosphor was synthesized by
      solid state reaction. The crystal structural and photoluminescence (PL)
      properties of KAB:Eu(2+) phosphor, as well as its thermal properties of the
      photoluminescence, were investigated. The KAB:Eu(2+) phosphor exhibits broad
      excitation spectra ranging from 230 to 420 nm, and an intense asymmetric blue
      emission band centered at 450 nm under lambdaex = 325 nm. Two different Eu(2+)
      emission centers in KAB:Eu(2+) phosphor were confirmed via their fluorescence
      decay lifetimes. The optimal concentration of Eu(2+) ions in K2-xEuxAl2B2O7 was
      determined to be x = 0.04 (2 mol %), and the corresponding concentration
      quenching mechanism was verified to be the electric dipole-dipole interactions.
      The PL intensity of the nonoptimized KAB:0.04Eu(2+) phosphor was measured to be
      ~58% that of the commercial blue-emitting BaMgAl10O17:Eu(2+) phosphor, and this
      phosphor has high color purity with the CIE coordinate (0.147, 0.051). When
      heated up to 150  degrees C, the KAB:0.04Eu(2+) phosphor still has 82% of the
      initial PL intensity at room temperature, indicating its high thermal stability.
      These results suggest that the KAB:Eu(2+) is a promising candidate as a blue
      emitting n-UV convertible phosphor for application in white light emitting
      diodes. 

PMID- 25751731
TI  - The reverse evolution from multicellularity to unicellularity during
      carcinogenesis.
AB  - Theoretical reasoning suggests that cancer may result from a knockdown of the
      genetic constraints that evolved for the maintenance of metazoan
      multicellularity. By characterizing the whole-life history of a xenograft tumour,
      here we show that metastasis is driven by positive selection for general loss-of
      function mutations on multicellularity-related genes. Expression analyses reveal
      mainly downregulation of multicellularity-related genes and an evolving
      expression profile towards that of embryonic stem cells, the cell type resembling
      unicellular life in its capacity of unlimited clonal proliferation. Also, the
      emergence of metazoan multicellularity ~600 Myr ago is accompanied by an elevated
      birth rate of cancer genes, and there are more loss-of-function tumour
      suppressors than activated oncogenes in a typical tumour. These data collectively
      suggest that cancer represents a loss-of-function-driven reverse evolution back
      to the unicellular 'ground state'. This cancer evolution model may account for
      inter-/intratumoural genetic heterogeneity, could explain distant-organ
      metastases and hold implications for cancer therapy. 

PMID- 25751732
TI  - Visual object imagery and autobiographical memory: Object Imagers are better at
      remembering their personal past.
AB  - In the present study we examined whether higher levels of object imagery, a
      stable characteristic that reflects the ability and preference in generating
      pictorial mental images of objects, facilitate involuntary and voluntary
      retrieval of autobiographical memories (ABMs). Individuals with high (High-OI)
      and low (Low-OI) levels of object imagery were asked to perform an involuntary
      and a voluntary ABM task in the laboratory. Results showed that High-OI
      participants generated more involuntary and voluntary ABMs than Low-OI, with
      faster retrieval times. High-OI also reported more detailed memories compared to
      Low-OI and retrieved memories as visual images. Theoretical implications of these
      findings for research on voluntary and involuntary ABMs are discussed. 

PMID- 25751733
TI  - Comparison of Hybrid-III and postmortem human surrogate response to simulated
      underbody blast loading.
AB  - Response of the human body to high-rate vertical loading, such as military
      vehicle underbody blast (UBB), is not well understood because of the chaotic
      nature of such events. The purpose of this research was to compare the response
      of postmortem human surrogates (PMHS) and the Hybrid-III anthropomorphic test
      device (ATD) to simulated UBB loading ranging from 100 to 860 g seat and floor
      acceleration. Data from 13 whole body PMHS tests were used to create response
      corridors for vertical loading conditions for the pelvis, T1, head, femur, and
      tibia; these responses were compared to Hybrid-III responses under matched
      loading conditions. 

PMID- 25751736
TI  - Generations: Academic and Athletic Integration of a Southern PWI Basketball
      Program.
AB  - PURPOSE: The purposes of this study were to: (a) analyze the insights and
      experiences of the 1st African American student-athlete (in basketball) at a
      prominent predominantly White institution in the Deep South as well as the later
      insights and experiences of his sons at the same university; and (b) to present a
      counterstory to the dominant historical rendering of the Civil Rights Movement,
      the integration of athletics, and the experiences and outcomes of contemporary
      African American athletes. METHOD: Using qualitative critical race methodology,
      investigators conducted and analyzed interviews with the 1st African American to
      play basketball at a prominent university located in the Deep South and his 2
      sons who attended the same university a generation later. RESULTS: Using the lens
      of critical race theory, the themes conceived from the analysis were the
      counterstory of agency, counterstorytelling stereotypes, and the salience of
      everyday racism. CONCLUSION: Racism is still existent within society, even within
      college athletics. The holistic success of African American athletes in college
      is dependent upon their ability to navigate overt and covert racial climates.

PMID- 25751735
TI  - Precision across race, age and gender of a HIV risk screen for adolescents and
      young adults.
AB  - Identification of adolescents and young adults at high risk for HIV infection in
      South Africa is a key component of current and future prevention efforts. A 5
      item measure was developed in the current study with acceptable levels of
      reliability and validity, and all items discriminating sufficiently between
      respondents at different levels of risk. However, both uniform and non-uniform
      differential item functioning (DIF) were revealed as problems: items performed
      differently by age, race, and gender groups. Consequently age-, race-, and gender
      specific percentile-based norms were developed. Implications for policy and
      practice are discussed. 

PMID- 25751734
TI  - Isolevuglandin-type lipid aldehydes induce the inflammatory response of
      macrophages by modifying phosphatidylethanolamines and activating the receptor
      for advanced glycation endproducts.
AB  - AIMS: Increased lipid peroxidation occurs in many conditions associated with
      inflammation. Because lipid peroxidation produces lipid aldehydes that can induce
      inflammatory responses through unknown mechanisms, elucidating these mechanisms
      may lead to development of better treatments for inflammatory diseases. We
      recently demonstrated that exposure of cultured cells to lipid aldehydes such as
      isolevuglandins (IsoLG) results in the modification of phosphatidylethanolamine
      (PE). We therefore sought to determine (i) whether PE modification by
      isolevuglandins (IsoLG-PE) occurred in vivo, (ii) whether IsoLG-PE stimulated the
      inflammatory responses of macrophages, and (iii) the identity of receptors
      mediating the inflammatory effects of IsoLG-PE. RESULTS: IsoLG-PE levels were
      elevated in plasma of patients with familial hypercholesterolemia and in the
      livers of mice fed a high-fat diet to induce obesity and hepatosteatosis. IsoLG
      PE potently stimulated nuclear factor kappa B (NFkappaB) activation and
      expression of inflammatory cytokines in macrophages. The effects of IsoLG-PE were
      blocked by the soluble form of the receptor for advanced glycation endproducts
      (sRAGE) and by RAGE antagonists. Furthermore, macrophages derived from the bone
      marrow of Ager null mice failed to express inflammatory cytokines in response to
      IsoLG-PE to the same extent as macrophages from wild-type mice. INNOVATION: These
      studies are the first to identify IsoLG-PE as a mediator of macrophage activation
      and a specific receptor, RAGE, which mediates its biological effects. CONCLUSION:
      PE modification by IsoLG forms RAGE ligands that activate macrophages, so that
      the increased IsoLG-PE generated by high circulating cholesterol levels or high
      fat diet may play a role in the inflammation associated with these conditions.

PMID- 25751737
TI  - Oxidative degradation of decabromodiphenyl ether (BDE 209) by potassium
      permanganate: reaction pathways, kinetics, and mechanisms assisted by density
      functional theory calculations.
AB  - This study found that decabromodiphenyl ether (BDE 209) could be oxidized
      effectively by potassium permanganate (KMnO4) in sulfuric acid medium. A total of
      15 intermediate oxidative products were detected. The reaction pathways were
      proposed, which primarily included cleavage of the ether bond to form
      pentabromophenol. Direct oxidation on the benzene ring also played an important
      role because hydroxylated polybrominated diphenyl ethers (PBDEs) were produced
      during the oxidation process. The degradation occurred dramatically in the first
      few minutes and fitted pseudo-first-order kinetics. Increasing the water content
      decelerated the reaction rate, whereas increasing the temperature facilitated the
      reaction. In addition, density functional theory (DFT) was employed to determine
      the frontier molecular orbital (FMO) and frontier electron density (FED) of BDE
      209 and the oxidative products. The theoretical calculation results confirmed the
      proposed reaction pathways. 

PMID- 25751738
TI  - Nitrite dismutase reaction mechanism: kinetic and spectroscopic investigation of
      the interaction between nitrophorin and nitrite.
AB  - Nitrite is an important metabolite in the physiological pathways of NO and other
      nitrogen oxides in both enzymatic and nonenzymatic reactions. The ferric heme b
      protein nitrophorin 4 (NP4) is capable of catalyzing nitrite disproportionation
      at neutral pH, producing NO. Here we attempt to resolve its disproportionation
      mechanism. Isothermal titration calorimetry of a gallium(III) derivative of NP4
      demonstrates that the heme iron coordinates the first substrate nitrite. Contrary
      to previous low-temperature EPR measurements, which assigned the NP4-nitrite
      complex electronic configuration solely to a low-spin (S = 1/2) species,
      electronic absorption and resonance Raman spectroscopy presented here demonstrate
      that the NP4-NO2(-) cofactor exists in a high-spin/low-spin equilibrium of 7:3
      which is in fast exchange in solution. Spin-state interchange is taken as
      evidence for dynamic NO2(-) coordination, with the high-spin configuration (S =
      5/2) representing the reactive species. Subsequent kinetic measurements reveal
      that the dismutation reaction proceeds in two discrete steps and identify an
      {FeNO}(7) intermediate species. The first reaction step, generating the {FeNO}(7)
      intermediate, represents an oxygen atom transfer from the iron bound nitrite to a
      second nitrite molecule in the protein pocket. In the second step this
      intermediate reduces a third nitrite substrate yielding two NO molecules. A
      nearby aspartic acid residue side-chain transiently stores protons required for
      the reaction, which is crucial for NPs' function as nitrite dismutase. 

PMID- 25751739
TI  - Galactose protects hepatocytes against TNF-alpha-induced apoptosis by promoting
      activation of the NF-kappaB signaling pathway in acute liver failure.
AB  - Saccharides are reported to protect hepatocytes from acute liver injury through
      distinct mechanisms. To date, the protective role of galactose against acute
      liver injury induced by lipopolysaccharide (LPS) and D-galactosamine (D-GalN) has
      been attributed to competition with D-GalN. Here, we showed that in addition to
      its effects on LPS/D-GalN and tumor necrosis factor alpha (TNF-alpha)/D-GalN
      models, galactose improves hepatic injury in mice challenged with LPS alone or
      TNF-alpha/actinomycin D. Consistent with this result, galactose enhanced the
      viability of TNF-alpha-stimulated Chang Liver and Hu7.5 hepatic cell lines.
      Specifically, galactose prevented TNF-alpha-induced apoptosis of hepatocytes
      through promoting phosphorylation of nuclear factor kappa B (NF-kappaB) p65.
      Additionally, galactose enhanced expression of the anti-apoptotic genes, c-IAP1
      and A20, and inhibited cleavage of caspase-8 and caspase-3. These findings
      collectively suggest that galactose prevents TNF-alpha-induced liver injury
      through activation of the NF-kappaB signaling pathway. Considering that
      monosaccharides protect against liver injury via distinct mechanisms, these
      compounds may represent a promising clinical approach to treat acute liver
      failure. 

PMID- 25751740
TI  - Recombinant human MFG-E8 ameliorates colon damage in DSS- and TNBS-induced
      colitis in mice.
AB  - Inflammatory bowel disease (IBD) is characterized by chronic inflammation of the
      digestive system and typically requires lifelong medical care. Recombinant human
      MFG-E8 (rhMFG-E8) is a 364-amino acid protein, which promotes apoptotic cell
      clearance and reduces inflammation. This study investigates the therapeutic
      effect of rhMFG-E8 on two well-established mouse models of IBD. Acute mucosal
      injury leading to colitis was caused by exposing C57BL/6 mice to 4% dextran
      sodium sulfate (DSS) in the drinking water over 7 days, and BALB/c mice to a
      single intrarectal dose of 2.75 mg of 2,4,6-trinitrobenzene sulfonic acid (TNBS).
      Upon clinical onset of colitis (day 2 in the DSS model and day 1 in the TNBS
      model), mice were treated with daily subcutaneous injections of rhMFG-E8 (60 or
      120 MUg/kg/day) or vehicle (saline) for 6 days. Treatment with rhMFG-E8
      significantly attenuated colitis in both models in a dose-dependent way.
      Treatment of DSS-induced colitis with rhMFG-E8 (120 MUg/kg/day) decreased weight
      loss by 59%, the colitis severity score by 71%, and colon shrinkage by 49% when
      compared with vehicle. Similarly, treatment of TNBS-induced colitis with rhMFG-E8
      (120 MUg/kg/day) decreased weight loss by 97%, the colitis severity score by 82%,
      and colon shrinkage by 62% when compared with vehicle. In both models, the colons
      of animals receiving rhMFG-E8 showed marked reduction in neutrophil infiltration,
      cytokine and chemokine expression, and apoptotic cell counts. In conclusion,
      rhMFG-E8 ameliorates DSS- and TNBS-induced colitis, suggesting that it has the
      potential to become a novel therapeutic agent for IBD.

PMID- 25751742
TI  - A low-cost method for estimating energy expenditure during soccer refereeing.
AB  - This study aimed to apply a validated bioenergetics model of sprint running to
      recordings obtained from commercial basic high-sensitivity global positioning
      system receivers to estimate energy expenditure and physical activity variables
      during soccer refereeing. We studied five Italian fifth division referees during
      20 official matches while carrying the receivers. By applying the model to the
      recorded speed and acceleration data, we calculated energy consumption during
      activity, mass-normalised total energy consumption, total distance, metabolically
      equivalent distance and their ratio over the entire match and the two halves.
      Main results were as follows: (match) energy consumption = 4729 +/- 608 kJ, mass
      normalised total energy consumption = 74 +/- 8 kJ . kg(-1), total distance =
      13,112 +/- 1225 m, metabolically equivalent distance = 13,788 +/- 1151 m and
      metabolically equivalent/total distance = 1.05 +/- 0.05. By using a very low-cost
      device, it is possible to estimate the energy expenditure of soccer refereeing.
      The provided predicting mass-normalised total energy consumption versus total
      distance equation can supply information about soccer refereeing energy demand. 

PMID- 25751741
TI  - A ten-year follow-up of a study of memory for the attack of September 11, 2001:
      Flashbulb memories and memories for flashbulb events.
AB  - Within a week of the attack of September 11, 2001, a consortium of researchers
      from across the United States distributed a survey asking about the circumstances
      in which respondents learned of the attack (their flashbulb memories) and the
      facts about the attack itself (their event memories). Follow-up surveys were
      distributed 11, 25, and 119 months after the attack. The study, therefore,
      examines retention of flashbulb memories and event memories at a substantially
      longer retention interval than any previous study using a test-retest
      methodology, allowing for the study of such memories over the long term. There
      was rapid forgetting of both flashbulb and event memories within the first year,
      but the forgetting curves leveled off after that, not significantly changing even
      after a 10-year delay. Despite the initial rapid forgetting, confidence remained
      high throughout the 10-year period. Five putative factors affecting flashbulb
      memory consistency and event memory accuracy were examined: (a) attention to
      media, (b) the amount of discussion, (c) residency, (d) personal loss and/or
      inconvenience, and (e) emotional intensity. After 10 years, none of these factors
      predicted flashbulb memory consistency; media attention and ensuing conversation
      predicted event memory accuracy. Inconsistent flashbulb memories were more likely
      to be repeated rather than corrected over the 10-year period; inaccurate event
      memories, however, were more likely to be corrected. The findings suggest that
      even traumatic memories and those implicated in a community's collective identity
      may be inconsistent over time and these inconsistencies can persist without the
      corrective force of external influences.

PMID- 25751744
TI  - Using the Assessment for Signal Clients as a feedback tool for reducing treatment
      failure.
AB  - OBJECTIVE: The Clinical Support Tools (CSTs) were developed to help therapists
      organize and target potential problems that might account for negative outcomes
      in psychotherapy. The core of CST feedback is the Assessment for Signal Clients.
      The purpose of this study was to describe and identify patterns of problems that
      typically characterize off-track cases. METHOD: The responses and scores from 107
      off-track clients from a hospital-based outpatient clinic were analyzed. RESULTS:
      A cluster analysis of the 107 off-track clients revealed three client types:
      those whose problems were characterized by alliance and motivational
      difficulties; those characterized by social support and life event difficulties;
      and those whose problems had an indistinguishable pattern. Log-linear modeling
      showed that if patients had less therapeutic alliance problems they were also
      less likely to have motivational problems. Findings were also consistent with the
      cluster analysis, which showed that a relatively higher percentage of not-on
      track participants received signal alerts for the social support items and scale.
      CONCLUSIONS: Individuals whose progress goes off-track while in psychotherapy
      appear to have their greatest difficulty with social support, followed closely by
      motivation for therapy and therapeutic alliance.

PMID- 25751743
TI  - Bmi1 limits dilated cardiomyopathy and heart failure by inhibiting cardiac
      senescence.
AB  - Dilated cardiomyopathy (DCM) is the most frequent cause of heart failure and the
      leading indication for heart transplantation. Here we show that epigenetic
      regulator and central transcriptional instructor in adult stem cells, Bmi1,
      protects against DCM by repressing cardiac senescence. Cardiac-specific Bmi1
      deletion induces the development of DCM, which progresses to lung congestion and
      heart failure. In contrast, Bmi1 overexpression in the heart protects from
      hypertrophic stimuli. Transcriptome analysis of mouse and human DCM samples
      indicates that p16(INK4a) derepression, accompanied by a senescence-associated
      secretory phenotype (SASP), is linked to severely impaired ventricular dimensions
      and contractility. Genetic reduction of p16(INK4a) levels reverses the pathology
      of Bmi1-deficient hearts. In parabiosis assays, the paracrine senescence response
      underlying the DCM phenotype does not transmit to healthy mice. As senescence is
      implicated in tissue repair and the loss of regenerative potential in aging
      tissues, these findings suggest a source for cardiac rejuvenation. 

PMID- 25751745
TI  - Size and aspect ratio control of Pd2Sn nanorods and their water denitration
      properties.
AB  - Monodisperse Pd2Sn nanorods with tuned size and aspect ratio were prepared by co
      reduction of metal salts in the presence of trioctylphosphine, amine, and
      chloride ions. Asymmetric Pd2Sn nanostructures were achieved by the selective
      desorption of a surfactant mediated by chlorine ions. A preliminary evaluation of
      the geometry influence on catalytic properties evidenced Pd2Sn nanorods to have
      improved catalytic performance. In view of these results, Pd2Sn nanorods were
      also evaluated for water denitration. 

PMID- 25751746
TI  - Measles at Disneyland, a problem for all ages.

PMID- 25751748
TI  - Rising to the challenge: Deep acting is more beneficial when tasks are appraised
      as challenging.
AB  - Cumulative research indicates that deep acting has a nonsignificant relationship
      with employee exhaustion, despite arguments that deep acting can be beneficial.
      To illuminate when deep acting leads to more positive employee outcomes, we draw
      on the resource conservation perspective to propose a within-individual model of
      deep acting that focuses on service employees' daily fluctuation of emotional
      labor and emotional exhaustion. Specifically, we propose that the ongoing
      experience of felt challenge is a within-person boundary condition that moderates
      deep acting's relationship with emotional exhaustion, and model emotional
      exhaustion as a mediating mechanism that subsequently predicts momentary job
      satisfaction and daily customer conflict handling. Using an experience sampling
      design, we collected data from 84 service employees over a 3-week period. Deep
      acting was less emotionally exhausting for service providers when they saw their
      tasks as more challenging. Furthermore, emotional exhaustion mediated the deep
      acting by felt challenge interaction effect on momentary job satisfaction and
      daily customer conflict handling. The findings contribute to a better
      understanding of the deep acting experience at work, while highlighting customer
      conflict handling as a key behavioral outcome of emotional labor.

PMID- 25751747
TI  - The methyltransferase Ezh2 controls cell adhesion and migration through direct
      methylation of the extranuclear regulatory protein talin.
AB  - A cytosolic role for the histone methyltransferase Ezh2 in regulating lymphocyte
      activation has been suggested, but the molecular mechanisms underpinning this
      extranuclear function have remained unclear. Here we found that Ezh2 regulated
      the integrin signaling and adhesion dynamics of neutrophils and dendritic cells
      (DCs). Ezh2 deficiency impaired the integrin-dependent transendothelial migration
      of innate leukocytes and restricted disease progression in an animal model of
      multiple sclerosis. Direct methylation of talin, a key regulatory molecule in
      cell migration, by Ezh2 disrupted the binding of talin to F-actin and thereby
      promoted the turnover of adhesion structures. This regulatory effect was
      abolished by targeted disruption of the interactions of Ezh2 with the
      cytoskeletal-reorganization effector Vav1. Our studies reveal an unforeseen
      extranuclear function for Ezh2 in regulating adhesion dynamics, with implications
      for leukocyte migration, immune responses and potentially pathogenic processes. 

PMID- 25751749
TI  - Modeling reciprocal team cohesion-performance relationships, as impacted by
      shared leadership and members' competence.
AB  - Despite the lengthy history of team cohesion-performance research, little is
      known about their reciprocal relationships over time. Using meta-analysis, we
      synthesize findings from 17 CLP design studies, and analyze their results using
      SEM. Results support that team cohesion and performance are related reciprocally
      with each other over time. We then used longitudinal data from 205 members of 57
      student teams who competed in a complex business simulation over 10 weeks, to
      test: (a) whether team cohesion and performance were related reciprocally over
      multiple time periods, (b) the relative magnitude of those relationships, and (c)
      whether they were stable over time. We also considered the influence of team
      members' academic competence and degree of shared leadership on these dynamics.
      As anticipated, cohesion and performance were related positively, and
      reciprocally, over time. However, the cohesion -> performance relationship was
      significantly higher than the performance -> cohesion relationship. Moreover, the
      cohesion -> performance relationship grew stronger over time whereas the
      performance -> cohesion relationship remained fairly consistent over time. As
      expected, shared leadership related positively to team cohesion but not directly
      to their performance; whereas average team member academic competence related
      positively to team performance but was unrelated to team cohesion. Finally, we
      conducted and report a replication using a second sample of students competing in
      a business simulation. Our earlier substantive relationships were mostly
      replicated, and we illustrated the dynamic temporal properties of shared
      leadership. We discuss these findings in terms of theoretical importance, applied
      implications, and directions for future research.

PMID- 25751750
TI  - Mindfulness buffers retaliatory responses to injustice: A regulatory approach.
AB  - We investigate the role of mindfulness as a regulatory factor by examining
      whether it mitigates the relationship between justice and retaliation. Drawing on
      theories of self-regulation, we integrate work on justice with emerging
      frameworks that identify mindfulness as an important work-related regulatory
      variable (Glomb, Duffy, Bono, & Yang, 2011). Specifically, we identify the role
      of mindfulness as a buffer of the ruminative thoughts and negative emotions that
      link injustice to retaliation. We test mediated moderation hypotheses in 2
      samples. In Sample 1, two behavioral measures of retaliation are assessed in an
      experiment that manipulated both injustice and mindfulness. In Sample 2, we
      generalize our model to the field, examining employee responses regarding
      experiences with workplace injustice and retaliation. Results of both studies
      converge to support the proposed mediated moderation model that mindfulness
      buffers the effect of injustice on rumination and negative emotions, thus
      reducing retaliation. Our findings contribute to the broader literatures on self
      regulation, organizational justice, and retaliation.

PMID- 25751751
TI  - Weight isn't selling: The insidious effects of weight stigmatization in retail
      settings.
AB  - In recent years, the literature on the stigma of obesity has grown but there
      still remains a paucity of research examining specific issues associated with its
      impact in the workplace. In the current study, we examine 3 such issues related
      to the influence of weight-based stigmatization in retail settings. First, we
      highlight research on the impact of obesity in men often is minimized or
      altogether excluded, and we examine whether weight-based stigmatization
      influences men in authentic retail settings (Study 1). Across retail contexts,
      Study 1 reveals that heavy (vs. nonheavy) men do experience significantly more
      interpersonal (subtle) discrimination. Second, we examine the "why" of weight
      based stigmatization and find that weight-related negative stereotypes compound
      to produce indirect but strong effects of stigmatization in retail settings
      (Study 2). Third and finally, we examine whether weight-based stigmatization
      against men and women in retail also influences ratings of associated products
      and the organizations for which heavy individuals work (also Study 2). Results
      from Study 2 show that stereotypes work similarly for men and women and that a
      stigma-by-association effect occurs in which evaluators rate products and
      organizations associated with heavy (vs. nonheavy) retail personnel more
      negatively. Finally, we discuss the importance of these findings in gaining a
      more holistic look at the influence of weight stigmatization in the workplace.

PMID- 25751752
TI  - Knowledge and motivation: two elements of health literacy that remain low with
      regard to nurse practitioners in Australia.
AB  - OBJECTIVE: This paper presents analysis of consumer focus groups that were
      undertaken as a part of the project to develop the now current Nursing and
      Midwifery Board of Australia's Nurse Practitioner Standards for Practice.
      METHODS: Six focus groups were conducted with consumers around Australia,
      including urban and remote areas. One purpose for these groups was to explore
      what was known of nurse practitioners and whether consumers could articulate the
      difference between the regulated titles of enrolled nurse, registered nurse and
      nurse practitioner. RESULTS: Consumers' knowledge of nurses' roles in the
      Australian primary healthcare system, and hence system literacy (particularly in
      terms of navigating the system), was low. Of perhaps greatest importance is the
      fact that those consumers with low health systems literacy also exhibited a low
      level of motivation to seek new knowledge. Many consumers relied on the medical
      profession to direct care. CONCLUSION: The low levels of health literacy raise
      questions of how to meaningfully include health consumers in innovative health
      related policy work.

PMID- 25751753
TI  - Characterization of tissue and slide artifacts from automated embedding systems.
AB  - With recent technological advances and cost reductions, automated embedding
      systems are rapidly becoming routine in the processing of skin biopsy specimens.
      The efficiency advantages of this technique are due in part to the use of
      patented sectionable cassettes that hold formalin-fixed tissue from the time of
      grossing through tissue sectioning. In this process, the final paraffin block
      contains both the tissue and the cassette, which are sectioned and stained in
      unison. Here, we report the multiple tissue and slide artifacts commonly seen
      with automated embedding systems that are unique to this method of tissue
      processing. The most frequently observed tissue changes are patterned molding of
      the biopsy specimen around the cassette material. The most common slide artifacts
      are due to the presence of geometrically shaped polarizable cassette material
      adjacent to or overlying the stained tissue. As many of these artifacts strongly
      resemble the shapes seen in the classic 1980s video game, Tetris, we propose the
      term of Tetris-like artifacts for these findings. Although we remain confident
      that use of an automated embedding system does not decrease diagnostic
      reliability, increased familiarity with the standard appearance of slides
      processed using this technique will help avoid confusion when evaluating these
      cases. 

PMID- 25751754
TI  - South Sea Atolls.

PMID- 25751755
TI  - Development and testing of a fully gravitational submerged anaerobic membrane
      bioreactor for wastewater treatment.
AB  - A gravity-operated submerged anaerobic membrane bioreactor (SAnMBR) was set up in
      order to test its principle of operation as an alternative to conventional pumped
      permeation of the membrane. This operating mode allowed the membrane flux rate to
      be measured accurately whilst maintaining a constant transmembrane pressure
      (TMP), and allowed small transient variations in the flux rate to be observed.
      The reactor was operated at 36 degrees C for a period of 115 days using a
      nutrient-balanced synthetic substrate with a high suspended solids concentration.
      Membrane cleaning was in situ by a gas scouring system using recirculation of
      headspace biogas. With an initial TMP of 7.0 kPa, the membrane flux slowly
      decreased due to membrane fouling and had not reached a constant value by day 71.
      The results indicated that the system was still acclimatizing up to 50 days after
      start-up; but from that point onwards, performance parameters became much more
      stable. A constant flux of 2.2 L m(-2) h(-1) was achieved over the last 45 days
      after the TMP was reduced to 2.3 kPa. The stable flux was maintained over this
      period and the loading raised to 1 g COD L(-1) d(-1) by increasing the influent
      strength. Under these conditions, the average chemical oxygen demand removal
      efficiency was 96% and the specific methane potential was 0.31 L CH4 g(-1) COD
      removed.

PMID- 25751756
TI  - The role of behavioural modification and exercise in the management of cancer
      related fatigue to reduce its impact during and after cancer treatment.
AB  - BACKGROUND: Fatigue is a symptom that can occur during treatment as an acute side
      effect but can also result in persistent fatigue as a long-term side effect or
      late effect. MATERIALS AND METHODS: We undertook a narrative review of the
      current literature and discuss the current evidence of assessment of fatigue and
      we specifically focus on the role of promoting behavioural change and focused
      rehabilitation to minimise these long-term effects and update the literature
      relating to this area from 2012 to date. RESULTS: We suggest there are
      behavioural change models that can be scaled up to enable patients to manage long
      term fatigue using exercise. However, from this updated review there are
      limitations to the current infrastructure and evidence base that will impact on
      the ability to do this. CONCLUSION: We continually need to raise awareness
      amongst health professionals to continue to suggest modifications to impact on
      fatigue at all stages of cancer treatment and into survivorship and late effects.
      These can range from simple brief interventions suggested in the clinic to full
      scale rehabilitation programmes if the correct infrastructure is available.
      Whichever approach is adopted we suggest exercise will be the mainstay of the
      treatment of fatigue in this group.

PMID- 25751757
TI  - Chemotherapy-induced peripheral neuropathy in patients treated with taxanes and
      platinum derivatives.
AB  - BACKGROUND: Chemotherapy with taxanes and platinum compounds has resulted in
      substantial survival benefits both in adjuvant and metastatic settings. However,
      as a side effect, such chemotherapy may cause peripheral neuropathy (CIPN) which
      may result in discontinuation of treatment, and if it persists after treatment
      completion, has a negative impact on quality of life (QoL). RESULTS: Symptoms of
      CIPN are sensory, like pain, numbness, and tingling, typically located in the
      hands and feet. For oxaliplatin, there is an acute form of CIPN, resulting in
      paraesthesias in the mouth and throat during or shortly after the infusion
      triggered by exposure to cold. Risks factors for CIPN include preexisting
      neuropathy, either from treatment with other neurotoxic agents, or from comorbid
      conditions. The incidence of CIPN is related to dose per cycle, cumulative dose,
      and duration of infusion. While cisplatin-induced neuropathy is irreversible,
      CIPN induced by taxanes may persist for several years in about 30% of patients.
      Evidence from the literature is suggestive that CIPN is likely to be negatively
      associated with QoL. No agents have been identified to be recommended for the
      prevention of CIPN. For treatment of CIPN, the best available data supports a
      moderate recommendation for treatment with duloxetine and evidence is
      inconclusive regarding the use of tricyclic antidepressants (such as
      nortriptyline), gabapentin, and a compounded topical gel containing baclofen,
      amitriptyline HCL, and ketamine. CONCLUSION: Research is still needed to predict
      which patients are at high risk of developing CIPN during treatment and in whom
      CIPN will persist after completion of chemotherapy.

PMID- 25751758
TI  - Integrated care pathways for cancer survivors - a role for patient-reported
      outcome measures and health informatics.
AB  - Modern cancer treatments have improved survival rates and changed the nature of
      cancer care. The acute and long-term physical and psychosocial comorbidities
      associated with treatment place increasing demands on healthcare services to
      provide suitable models of follow-up care for the survivor population. AIM: We
      discuss the value and challenges of incorporating patient-reported outcome
      measures (PROMs) and eHealth interventions into routine follow-up care. We draw
      on our 15 years' experience of developing electronic systems for capturing
      patient-reported data in oncology settings, with particular reference to eRAPID a
      new online symptom reporting system for cancer patients. THE REDESIGN OF
      HEALTHCARE PATHWAYS: New stratified care pathways have been proposed for cancer
      survivors with an emphasis on supported self-management and shared care. THE
      POTENTIAL ROLE OF PROMS IN SURVIVORSHIP CARE PATHWAYS: PROMs can be used to
      evaluate rehabilitation services, provide epidemiological 'Big Data' and screen
      patients for physical and psychological morbidities to determine the need for
      further support. In addition, electronic PROMs systems linked to electronic
      patient records (EPRs) have the capability to provide tailored self-management
      advice to individual patients. INTEGRATION OF PROMS INTO CLINICAL PRACTICE: The
      successful clinical utilisation of PROMs is dependent on a number of components
      including; choosing appropriate questionnaires, developing evidence-based scoring
      algorithms, the creation of robust electronic platforms for recording and
      transferring data into EPRs, and training staff and patients to engage
      effectively with PROMs. DISCUSSION: There is increasingly positive evidence for
      using PROMs and eHealth approaches to support cancer patients' care during
      treatment. Much of what has been learnt can be applied to cancer survivorship.
      PROMs integrated into eHealth platforms and with EPR have the potential to play a
      valuable role in the development of appropriate and sustainable long-term follow
      up models for cancer survivors.

PMID- 25751759
TI  - Treatment-related cardiovascular late effects and exercise training
      countermeasures in testicular germ cell cancer survivorship.
AB  - BACKGROUND: Treatment of testicular germ cell cancer constitutes a major success
      story in modern oncology. Today, the vast majority of patients are cured by a
      therapeutic strategy using one or more highly effective components including
      surgery (orchiectomy), radiotherapy and/or chemotherapy. However, the excellent
      cancer-specific survival comes at considerable costs, as individuals with a
      history of germ cell cancer experience serious long-term complications, including
      markedly increased risk of cardiovascular morbidities and premature
      cardiovascular death. The factors responsible, as well as their mode of action,
      are not fully understood and there is a lack of knowledge concerning optimal
      evidence-based long-term follow-up strategies. RESULTS: Here, we present the
      growing body of evidence suggesting that germ cell cancer patients as a
      consequence of the different treatment components, are subjected to toxicities,
      which individually, and synergistically, can cause physiological impairments
      leading to sub-clinical or clinical cardiovascular disorders (i.e. the 'multiple
      hit hypothesis'). Furthermore, we discuss the efficacy and utility of structured
      exercise training to ameliorate treatment-induced cardiovascular dysfunction to
      prevent premature onset of clinical cardiovascular disease in germ cell cancer
      survivors, with a view towards highlighting future directions of exercise-based
      survivorship research in the germ cell cancer setting. CONCLUSION: As exercise
      training may have the potential to ameliorate and/or reverse long-term
      cardiovascular disease sequelae in germ cell cancer survivors, a strong rationale
      exists for the promotion of exercise oncology research in this setting, in order
      to provide exercise recommendations for optimal germ cell cancer survivorship.

PMID- 25751760
TI  - Cancer survivors' experience of exercise-based cancer rehabilitation - a meta
      synthesis of qualitative research.
AB  - BACKGROUND: Evidence for the safety and benefits of exercise training as a
      therapeutic and rehabilitative intervention for cancer survivors is accumulating.
      However, whereas the evidence for the efficacy of exercise training has been
      established in several meta-analyses, synthesis of qualitative research is
      lacking. In order to extend healthcare professionals' understanding of the
      meaningfulness of exercise in cancer survivorship care, this paper aims to
      identify, appraise and synthesize qualitative studies on cancer survivors'
      experience of participation in exercise-based rehabilitation. MATERIAL AND
      METHODS: Five electronic databases (PubMed, PsychINFO, EMBASE, Cinahl and Scopus)
      were searched systematically for articles published up to May 2014 using keywords
      and MeSH terms. To be included, studies had to contain primary data pertaining to
      patient experiences from participation in supervised, structured moderate to
      vigorous-intensity exercise. RESULTS: In total 2447 abstracts were screened and
      37 papers were read in full. Of these, 19 studies (n = 390) were selected for
      inclusion and critically appraised. Synthesis of data extracted from eight
      studies including in total 174 patients (77% women, age 28-76 years) exclusively
      reporting experiences of participation in structured, supervised exercise
      training resulted in nine themes condensed into three categories: 1) emergence of
      continuity; 2) preservation of health; and 3) reclaiming the body reflecting the
      benefits of exercise-based rehabilitation according to cancer survivors.
      Accordingly, the potential of rebuilding structure in everyday life, creating a
      normal context and enabling the individual to re-establish confidentiality and
      trust in their own body and physical potential constitute substantial qualities
      fundamental to the understanding of the meaningfulness of exercise-based
      rehabilitation from the perspective of patients. CONCLUSIONS: In addition to the
      accumulating evidence for the efficacy of exercise training in cancer
      rehabilitation, it is incumbent upon clinicians and policy-makers to acknowledge
      and promote the meaningfulness of exercise for the individual, and to use this
      knowledge to provide new solutions to current problems related to recruitment of
      underserved populations, long-term adherence and implementation.

PMID- 25751761
TI  - Dependence of the four-atom reaction HBr + OH -> Br + H2O on temperatures between
      20 and 2000 K.
AB  - A quasiclassical trajectory method is used to study the temperature dependence of
      HBr + OH -> Br + H2O using analytic forms of two-, three-, and four-body and long
      range interaction potentials. Below 300 K, the reaction is attraction-driven and
      occurs through formation of a collision complex BrH...OH, which is sufficiently
      long-lived to enhance H atom tunneling. Strong negative temperature dependence of
      the complex-mode rate is found between 20 and 300 K, consistent with experimental
      data reported by various authors. Above 300 K, the reaction occurs primarily
      through a direct-reaction mechanism. The sum of the complex- and direct-mode
      rates is shown to describe the reaction over the wide range 20-2000 K. The
      primary kinetic isotope effect is nearly constant with the normal H reaction
      faster by a factor of ~1.7 over the entire temperature range. The product energy
      distribution in vibration, rotation, and translation at 300 K is found to be 48,
      8, and 44%, respectively. The 1:1 resonance leads to efficient flow of energy
      between the stretching modes. Less than a quarter of the H2O vibrational energy
      deposits in the bending mode through intramolecular flow from the two stretching
      modes. 

PMID- 25751762
TI  - Synergy between TiO2 and Co(x)O(y) sites in electrocatalytic water decomposition.
AB  - A computational study of the cooperative effect of a small four-atom Co oxide
      cluster supported on the TiO2 anatase (100) surface in the electrochemical water
      splitting reaction is presented. The results have been obtained including
      explicit solvent water molecules by means of Car-Parrinello MD simulations.
      Reaction steps in the catalytic cycle determined involve the formation of TiO2
      surface hydroxyl groups as well as elementary reaction steps on the Co oxide
      cluster. Essential is the observation of O-O bond formation at the inter-phase of
      Co oxide particles and the TiO2 support. 

PMID- 25751763
TI  - Intriguing electronic properties of two-dimensional MoS2/TM2CO2 (TM = Ti, Zr, or
      Hf) hetero-bilayers: type-II semiconductors with tunable band gaps.
AB  - Two-dimensional (2D) transition metal compound (TMC) monolayers, as well as their
      van der Waals heterostructures with unique properties, are fundamentally and
      technologically intriguing. Here, heterostructures consisting of a MoS2 monolayer
      and TM2CO2 (TM = Ti, Zr or Hf) monolayers are systematically researched by means
      of the density functional theory (DFT). Different from semiconductor/metal
      contacts, MoS2 and TM2CO2 monolayers are all semiconductors with band gaps
      ranging from 0.25-1.67 eV. According to rigorous screening of stacking patterns,
      MoS2/Zr2CO2 is shown to be an indirect type-II semiconductor with the maximum
      valence and minimum conduction bands spatially separated on opposite monolayers.
      Simultaneously, the interface charges transfer from Zr2CO2 to MoS2 results in a
      built-in field that separates the electrons and holes efficiently. Also, the
      smaller effective masses of electrons and the holes of band edges indicate the
      higher carrier mobility. Moreover, strain regulation can make the hetero
      bilayer's character a semiconductor-semimetal-metal transition. The physical
      insights pave the way for the good performance of MoS2/TM2CO2 in next-generation
      electronic devices and photocatalysts. 

PMID- 25751764
TI  - Molecular design for moisture insensitivity of compositionally graded hybrid
      films.
AB  - Effective bonding of organic/inorganic interfaces especially in high humidity
      environments is paramount to the structural reliability of modern multilayer
      device technologies, such as flexible electronics, photovoltaics, microelectronic
      devices, and fiber-metal laminates used in aerospace applications. We demonstrate
      the ability to design compositionally graded hybrid organic/inorganic films with
      an inorganic zirconium network capable of forming a moisture-insensitive bond at
      the interface between an oxide and organic material. By controlling the chemistry
      of the deposited films and utilizing time-dependent debonding studies, we were
      able to correlate the behavior of the hybrid films at high humidity to their
      underlying molecular structure. As a result, an outstanding threefold improvement
      in adhesion of silicon/epoxy interfaces can be obtained with the introduction of
      these films even in high humidity environments. 

PMID- 25751765
TI  - CpG oligodeoxynucleotides as mucosal adjuvants.
AB  - Bacterial DNA comprising palindromic sequences and containing unmethylated CpG is
      recognized by toll-like receptor 9 of plasmacytoid dendritic cells (pDCs) and
      induces the production of interferon-alpha and chemokines, leading to the
      activation of a Th1 immune response. Therefore, synthetic equivalents of
      bacterial DNA (CpG oligodeoxynucleotides) have been developed for clinical
      applications. They are usually phosphorothioated for in vivo use; this approach
      also leads to adverse effects as reported in mouse models.Mucosal vaccines that
      induce both mucosal and systemic immunity received substantial attention in
      recent years. For their development, phosphodiester-linked oligodeoxynucleotides,
      including the sequence of a palindromic CpG DNA may be advantageous as adjuvants
      because their target pDCs are present right there, in the mucosa of the
      vaccination site. In addition, the probability of adverse effects is believed to
      be low. Here, we review the discovery of such CpG oligodeoxynucleotides and their
      possible use as mucosal adjuvants.

PMID- 25751767
TI  - Using simulation to improve patient safety: dawn of a new era.

PMID- 25751766
TI  - A small molecule that inhibits OGT activity in cells.
AB  - O-GlcNAc transferase (OGT) is an essential mammalian enzyme that regulates
      numerous cellular processes through the attachment of O-linked N
      acetylglucosamine (O-GlcNAc) residues to nuclear and cytoplasmic proteins. Its
      targets include kinases, phosphatases, transcription factors, histones, and many
      other intracellular proteins. The biology of O-GlcNAc modification is still not
      well understood, and cell-permeable inhibitors of OGT are needed both as research
      tools and for validating OGT as a therapeutic target. Here, we report a small
      molecule OGT inhibitor, OSMI-1, developed from a high-throughput screening hit.
      It is cell-permeable and inhibits protein O-GlcNAcylation in several mammalian
      cell lines without qualitatively altering cell surface N- or O-linked glycans.
      The development of this molecule validates high-throughput screening approaches
      for the discovery of glycosyltransferase inhibitors, and further optimization of
      this scaffold may lead to yet more potent OGT inhibitors useful for studying OGT
      in animal models. 

PMID- 25751769
TI  - Muscle Power Predicts Adolescent Bone Strength: Iowa Bone Development Study.
AB  - PURPOSE: To assess association between lower body muscle power and bone strength
      as well as the mediating effect of muscle cross-sectional area (MCSA) on that
      association. METHODS: Participants (141 males and 162 females) were approximately
      17 yr. Muscle power was predicted using vertical jump and the Sayers equation.
      Using peripheral quantitative computed tomography (pQCT), bone strength indices
      were obtained at two locations of the tibia, corresponding to primary stressors
      acting upon each site: bone strength index for compression (BSI) at the distal 4%
      site; density-weighted polar section modulus strength-strain index (SSIp) and
      cortical bone area (CoA) at the 66% midshaft site for torsion. Muscle cross
      sectional area was measured at the 66% site. Pearson bivariate and partial
      correlation coefficients were estimated to quantify the strength of the
      associations among variables. Direct and indirect mediation model effects were
      estimated, and 95% bootstrap confidence intervals were constructed to test the
      causal hypothesis. Height and maturity were examined as covariates. RESULTS:
      Pearson correlation coefficients among muscle power, MCSA, and bone strength were
      statistically significant (P < 0.01) and ranged from r = 0.54 to r = 0.78. After
      adjustment for covariates, associations were reduced (r = 0.37 to 0.69) (P <
      0.01). Mediation models for males for BSI, SSIp, and CoA accounted for 38%, 66%,
      and 54% of the variance in bone strength, respectively. Models for females for
      BSI, SSIp, and CoA accounted for 46%, 77%, and 66% of the variance, respectively.
      CONCLUSIONS: We found strong and consistent associations as well as direct and
      indirect pathways, among muscle power, MCSA, and tibia strength. These results
      support the use of muscle power as a component of health-related fitness in bone
      health interventions for older adolescents.

PMID- 25751768
TI  - Risk-adjusted operative delivery rates and maternal-neonatal outcomes as measures
      of quality assessment in obstetric care: a multicenter prospective study.
AB  - BACKGROUND: Although the evaluation of caesarean delivery rates has been
      suggested as one of the most important indicators of quality in obstetrics, it
      has been criticized because of its controversial ability to capture maternal and
      neonatal outcomes. In an "ideal" process of labor and delivery auditing, both
      caesarean (CD) and assisted vaginal delivery (AVD) rates should be considered
      because both of them may be associated with an increased risk of complications.
      The aim of our study was to evaluate maternal and neonatal outcomes according to
      the outlier status for case-mix adjusted CD and AVD rates in the same obstetric
      population. METHODS: Standardized data on 15,189 deliveries from 11 centers were
      prospectively collected. Multiple logistic regression was used to estimate the
      risk-adjusted probability of a woman in each center having an AVD or a CD.
      Centers were classified as "above", "below", or "within" the expected rates by
      considering the observed-to-expected rates and the 95% confidence interval around
      the ratio. Adjusted maternal and neonatal outcomes were compared among the three
      groupings. RESULTS: Centers classified as "above" or "below" the expected CD
      rates had, in both cases, higher adjusted incidence of composite maternal (2.97%,
      4.69%, 3.90% for "within", "above" and "below", respectively; p = 0.000) and
      neonatal complications (3.85%, 9.66%, 6.29% for "within", "above" and "below",
      respectively; p = 0.000) than centers "within" CD expected rates. Centers with
      AVD rates above and below the expected showed poorer and better composite
      maternal (3.96%, 4.61%, 2.97% for "within", "above" and "below", respectively; p
      = 0.000) and neonatal (6.52%, 9.77%, 3.52% for "within", "above" and "below",
      respectively; p = 0.000) outcomes respectively than centers with "within" AVD
      rates. CONCLUSIONS: Both risk-adjusted CD and AVD delivery rates should be
      considered to assess the level of obstetric care. In this context, both higher
      and lower-than-expected rates of CD and "above" AVD rates are significantly
      associated with increased risk of complications, whereas the "below" status for
      AVD showed a "protective" effect on maternal and neonatal outcomes.

PMID- 25751770
TI  - Physical Activity, Sedentary Time, and Obesity in an International Sample of
      Children.
AB  - PURPOSE: To determine the relationships between moderate-to-vigorous physical
      activity (MVPA), vigorous physical activity (VPA), sedentary time, and obesity in
      children from 12 countries representing a wide range of human development.
      METHODS: The sample included 6539 children age 9-11 yr. Times in MVPA, VPA, and
      sedentary behaviors were assessed by accelerometry. The body mass index (BMI;
      kg.m) was used to classify children as obese based on z-scores (> +2 SD) from
      World Health Organization reference data. RESULTS: The mean (SD) times spent in
      MVPA, VPA, and sedentary behavior were 60 (25) min.d, 18 (11) min.d, and 513 (69)
      min.d, respectively. The overall proportion of the sample that was obese ranged
      from 5.2% to 24.6% across sites. The odds ratios for obesity were significant for
      MVPA (0.49; 95% CI, 0.44-0.55), VPA (0.41; 0.37-0.46), and sedentary time (1.19;
      1.08-1.30) in the overall sample. The associations of MVPA and VPA with obesity
      were significant in all 12 sites, whereas the association between sedentary time
      and obesity was significant in five of the 12 sites. There was a significant
      difference in BMI z-scores across tertiles of MVPA (P < 0.001) but not across
      tertiles of sedentary time in a mutually adjusted model. The results of receiver
      operating characteristic curve analyses for obesity indicated that the optimal
      thresholds for MVPA (area under the curve [AUC], 0.64), VPA (AUC, 0.67) and
      sedentary behavior (AUC, 0.57) were 55 (95% CI, 50-64) min.d, 14 (11-16) min.d,
      and 482 (455-535) min.d, respectively. CONCLUSIONS: Greater MVPA and VPA were
      both associated with lower odds of obesity independent of sedentary behavior.
      Sedentary time was positively associated with obesity, but not independent of
      MVPA. Attaining at least 55 min.d of MVPA is associated with lower obesity in
      this multinational sample of children, which supports current guidelines.

PMID- 25751772
TI  - [Clinical-psychological components in the consideration of functional dysphonia-
      a review].
AB  - The etiopathogenesis of functional dysphonia is complex; it is not sufficient to
      look solely at vocal behavior aspects. The predisposing basis for functional
      dysphonia can lie in the constitution of an individual, his/her professional
      speaking and speech behavior and/or may be personality-based. (Prolonged)
      psychosocial stress, vocal overstressing, unfavorable speaking habits, infection
      of the upper respiratory tract, inflammatory processes in the larynx, emotional
      life events and COSO events are considered as possible triggers. The interaction
      of predisposed and causal factors is unknown. Stress, overall fatigue, anxiety,
      depression and/or certain personality traits (which complicate or hamper coping)
      are considered as perpetuating factors. In any case, overlaps between voice
      symptoms and reactive psychic as well as social problems have to be kept in mind
      (e. g. the burden of suffering, depressive processing, speaking anxiety, socially
      withdrawal). Because the association of multiple psychosocial factors with
      functional dysphonia is not distinct--such are always existent in organ medically
      unexplained symptoms--functional dysphonia has to be diagnostically
      differentiated. For the purpose of the article, a psycho-diagnostic path
      following the ICD-10 chapter V along general lines is presented. Until now, it is
      unknown which psychosocial factors discriminate a psychogenic dysphonia from
      muscle tension dysphonia.

PMID- 25751773
TI  - [From the expert's office: fixed prices for hearing aids in the National Health
      Insurance].

PMID- 25751774
TI  - [Manifestation of rheumatic diseases in the larynx].
AB  - Rheumatic disorders (rheumatoid arthritis, sarcoidosis, systemic lupus
      erythematosus, Wegener's granulomatosis, relapsing polychondritis) may affect the
      larynx. The clinical symptoms are often unspecific, leading to delayed diagnosis.
      Malignant tumours should be considered in differential diagnosis with
      necessitating biopsy. Treatment may require interdisciplinary approach together
      with a specialist in internal medicine and rheumatology.

PMID- 25751775
TI  - [Support--anesthesia, surgical situation, instruments, navigation equipment, etc.
      - Part 1].

PMID- 25751776
TI  - Association of Enterovirus 71 encephalitis with the interleukin-8 gene region in
      Chinese children.
AB  - The study was performed in 36 Chinese patients with Enterovirus 71 (EV71)
      encephalitis and 141 patients with EV71-related hand, foot and mouth disease
      (HFMD) without encephalitis. Genotyping was determined by polymerase chain
      reaction- restriction fragment length polymorphism. Patients with EV71
      encephalitis had a significantly higher frequency of interleukin-8 (IL-8)-251TT
      genotype than patients with EV71-related HFMD without encephalitis (55.6% vs
      31.2%, p = 0.023). The frequency of IL-8-251T alleles was significantly higher
      among patients with EV71 encephalitis than in patients with EV71-related HFMD
      without encephalitis (72.2% vs 58.9%, odds ratio 1.8, 95% confidence interval 1.0
      3.2, p = 0.038). There were significant differences in gender, age, fever days,
      white blood cell count, C-reactive protein and blood glucose concentration and IL
      8 levels among genotypes of IL-8-251A/T in EV71-infected patients, but no
      significant differences in alanine or aspartate aminotransferase, creatine kinase
      myocardial isozyme and cerebrospinal fluid in patients with EV71 encephalitis.
      These findings suggest that the IL-8-251T allele is associated with
      susceptibility to EV71 encephalitis in Chinese patients. 

PMID- 25751777
TI  - An OXA-48-producing Escherichia coli isolated from a Danish patient with no
      hospitalization abroad.
AB  - Carbapenemase-producing organisms are disseminating globally and are now emerging
      as a worrying threat in Scandinavia. Before August 2013, OXA-48-producing
      organisms had not been detected in Danish patients. Here we report the isolation
      of an ST746 OXA-48-producing Escherichia coli with the plasmid pOXA-48a carrying
      the blaOXA-48 gene isolated from a Danish patient without history of
      hospitalization abroad. The patient reported tourist travel to Egypt and Turkey.
      The potential acquisition of carbapenemase-producing organisms by ingestion of
      contaminated food is discussed. 

PMID- 25751778
TI  - My most informative error.

PMID- 25751779
TI  - The mesosphere and metals: chemistry and changes.

PMID- 25751780
TI  - Rph1 mediates the nutrient-limitation signaling pathway leading to
      transcriptional activation of autophagy.
AB  - To maintain proper cellular homeostasis, the magnitude of autophagy activity has
      to be finely tuned in response to environmental changes. Many aspects of
      autophagy regulation have been extensively studied: pathways integrating signals
      through the master regulators TORC1 and PKA lead to multiple post-translational
      modifications affecting the functions, protein-protein interactions, and
      localization of Atg proteins. The expression of several ATG genes increases
      sharply upon autophagy induction conditions, and defects in ATG gene expression
      are associated with various diseases, pointing to the importance of
      transcriptional regulation of autophagy. Yet, how changes in ATG gene expression
      affect the rate of autophagy is not well characterized, and transcriptional
      regulators of the autophagy pathway remain largely unknown. To identify such
      regulators, we analyzed the expression of several ATG genes in a library of DNA
      binding protein mutants. This led to the identification of Rph1 as a master
      transcriptional regulator of autophagy. 

PMID- 25751781
TI  - Chemical constituents and structural characterization of polysaccharides from
      four typical bamboo species leaves.
AB  - In order to find bamboo leaves with high contents of bioactive polysaccharides,
      32 samples were chosen to analyze their polysaccharide content by GC and sulfuric
      acid-anthrone colorimetric assays. Purified polysaccharides (BLPS) were separated
      from the four varieties P. nigra (Lodd.) Munro (PN), P. vivax McClure (PV),
      Chimonobambusa quadrangularis (Fenzi) Makino (CQ), and P. bambussoides cv.
      Tanakae (PB) by ultrasound extraction, solution precipitation, ion exchange
      resin, DEAE-52 and Sephadex G-100 chromatography. BLPS structural
      characterization was accomplished by HPLC-GPC, Fourier transform infra-red
      spectroscopy (FTIR) and NaIO4-HIO4 oxidation reactions. The results showed that
      the total polysaccharides of the bamboo leaves in samples 1-32 ranged between
      1.4% and 5.4%, Samples No. 29-No. 32 (PN, PV, CQ, and PB) contained 2-3 fold more
      polysaccharides than No. 1~No. 28 among the 32 different species, particularly
      the content of galactose was in a range of 21.5%-34.1% for these four typical
      bamboo species leaves, which was also more than 2-3 fold higher than in No. 1-No.
      28. Sugar analysis indicated that PN-PBLPS-1, PV-PBLPS-1, CQ-PBLPS-1 and PB-PBLPS
      1 from the four varieties were homogeneous polysaccharides with molecular weights
      of 2.04 * 104, 1.15 * 104, 8.75 * 104 and 1.48 * 104 Da, respectively. PB-PBLPS-1
      was a mixture of alpha-galactopyranose and beta-d-glucopyranose linkages with
      alpha-(1->6) or beta-(1->6)glycosidic bonds, while PN-PBLPS-1, PV-PBLPS-1, and CQ
      PBLPS-1 had alpha galactopyranose linkages with alpha-(1->6) glycosidic bonds. 

PMID- 25751782
TI  - Natural products for the treatment of trachoma and Chlamydia trachomatis.
AB  - The neglected tropical disease (NTD) trachoma is currently the leading cause of
      eye disease in the world, and the pathogenic bacteria causing this condition,
      Chlamydia trachomatis, is also the most common sexually transmitted pathogenic
      bacterium. Although the serovars of this bacterial species typically vary between
      ocular and genital infections there is a clear connection between genital C.
      trachomatis infections and the development of trachoma in infants, such that the
      solutions to these infections are closely related. It is the unique life cycle of
      the C. trachomatis bacteria which primarily leads to chronic infections and
      challenges in treatment using conventional antibiotics. This life cycle involves
      stages of infective elementary bodies (EBs) and reproductive reticulate bodies
      (RBs). Most antibiotics only target the reproductive RBs and this often leads to
      the need for prolonged therapy which facilitates the development of drug
      resistant pathogens. It is through combining several compounds to obtain multiple
      antimicrobial mechanisms that we are most likely to develop a reliable means to
      address all these issues. Traditional and ethnobotanical medicine provides
      valuable resources for the development of novel formulations and treatment
      regimes based on synergistic and multi-compound therapy. In this review we intend
      to summarize the existing literature on the application of natural compounds for
      controlling trachoma and inhibiting chlamydial bacteria and explore the potential
      for the development of new treatment modalities. 

PMID- 25751783
TI  - Assessing chemical constituents of Mimosa caesalpiniifolia stem bark: possible
      bioactive components accountable for the cytotoxic effect of M. caesalpiniifolia
      on human tumour cell lines.
AB  - Mimosa caesalpiniifolia is a native plant of the Brazilian northeast, and few
      studies have investigated its chemical composition and biological significance.
      This work describes the identification of the first chemical constituents in the
      ethanolic extract and fractions of M. caesalpiniifolia stem bark based on NMR, GC
      qMS and HRMS analyses, as well as an assessment of their cytotoxic activity. GC
      qMS analysis showed fatty acid derivatives, triterpenes and steroid substances
      and confirmed the identity of the chemical compounds isolated from the hexane
      fraction. Metabolite biodiversity in M. caesalpiniifolia stem bark revealed the
      differentiated accumulation of pentacyclic triterpenic acids, with a high content
      of betulinic acid and minor amounts of 3-oxo and 3beta-acetoxy derivatives.
      Bioactive analysis based on total phenolic and flavonoid content showed a high
      amount of these compounds in the ethanolic extract, and ESI-(-)-LTQ-Orbitrap-MS
      identified caffeoyl hexose at high intensity, as well as the presence of phenolic
      acids and flavonoids. Furthermore, the evaluation of the ethanolic extract and
      fractions, including betulinic acid, against colon (HCT-116), ovarian (OVCAR-8)
      and glioblastoma (SF-295) tumour cell lines showed that the crude extract, hexane
      and dichloromethane fractions possessed moderate to high inhibitory activity,
      which may be related to the abundance of betulinic acid. The phytochemical and
      biological study of M. caesalpiniifolia stem bark thus revealed a new alternative
      source of antitumour compounds, possibly made effective by the presence of
      betulinic acid and by chemical co-synergism with other compounds. 

PMID- 25751784
TI  - Pharmacokinetics and tissue distribution study of caudatin in normal and
      diethylnitrosamine-induced hepatocellular carcinoma model rats.
AB  - Caudatin is a potential antitumor agent isolated from the traditional Chinese
      medicine "baishouwu", which was the root tuber of Cynanchum auriculatum Royle ex
      Wight. In our previous studies, caudatin showed selectivity on human hepatoma
      cell line SMMC7721 among several different tumor cell lines, and further in vivo
      tests validated the inhibitory action of caudatin against hepatic cancer using an
      H22 solid tumor model in mice, but to our knowledge, the biopharmaceutical
      properties of caudatin are largely unknown. In this study, a simple, rapid and
      sensitive ultra-performance liquid chromatography-tandem mass spectrometry (UPLC
      MS/MS) method for the determination of caudatin in rat plasma and tissues, which
      kept the run time to detect one sample within 4 min, was developed and validated.
      Pharmacokinetics and tissue distribution studies of caudatin in conventional rats
      and hepatocellular carcinoma (HCC) model rats were then conducted for the first
      time. Statistically significant differences were observed between conventional
      rats and diethylnitrosamine (DEN)-induced HCC rats with respect to
      pharmacokinetic parameters, including maximum concentration (Cmax), time to reach
      Cmax (Tmax), half-life (t1/2), area under the concentration-time curve (AUC0-t,
      AUC0-infinity), mean residence time (MRT0-t and MRT0-infinity), and oral
      clearance (CL/F). Increased exposures of caudatin were found in the plasma and
      livers of HCC model rats, which would be helpful for a better understanding of
      pharmacological effect of caudatin in treating HCC disease. 

PMID- 25751785
TI  - A novel and effective chromatographic approach to the separation of isoflavone
      derivatives from Pueraria lobata.
AB  - A novel and effective chromatographic approach to the separation and purification
      of isoflavone compounds from Pueraria lobata is described. The method is based on
      flash chromatography (FC), coupled to preparative high performance liquid
      chromatography (prep-HPLC) via a six-way valve. The FC step comprised tandem
      reversed phase columns, pre-packed with MCI gel (Mitsubishi Chemical Corp.,
      Tokyo, Japan) and C18 (Fuji Silysia Chemical Ltd, Osaka, Japan) resin,
      respectively, and was designed to separate a crude Pueraria lobata extract into
      several preliminary fractions. Fractions containing the target compounds were
      then directly injected via the six-way valve into prep-HPLC columns, without
      further treatment, for final isolation and purification. Nine isoflavonoids were
      successfully isolated, three through an online mode and the other six through an
      offline mode. The purities of all compounds exceeded 95.0%, as determined by HPLC
      with an UV-vis photodiode array detector. The convenience, low solvent
      consumption, and time-saving advantages of this method offer an attractive and
      promising approach to the isolation of natural products. 

PMID- 25751786
TI  - Can we produce heparin/heparan sulfate biomimetics using "mother-nature" as the
      gold standard?
AB  - Heparan sulfate (HS) and heparin are glycosaminoglycans (GAGs) that are
      heterogeneous in nature, not only due to differing disaccharide combinations, but
      also their sulfate modifications. HS is well known for its interactions with
      various growth factors and cytokines; and heparin for its clinical use as an
      anticoagulant. Due to their potential use in tissue regeneration; and the recent
      adverse events due to contamination of heparin; there is an increased surge to
      produce these GAGs on a commercial scale. The production of HS from natural
      sources is limited so strategies are being explored to be biomimetically produced
      via chemical; chemoenzymatic synthesis methods and through the recombinant
      expression of proteoglycans. This review details the most recent advances in the
      field of HS/heparin synthesis for the production of low molecular weight heparin
      (LMWH) and as a tool further our understanding of the interactions that occur
      between GAGs and growth factors and cytokines involved in tissue development and
      repair. 

PMID- 25751787
TI  - Antioxidant Compounds from Vegetable Matrices: Biosynthesis, Occurrence, and
      Extraction Systems.
AB  - Natural antioxidants such as vitamin C, tocopherols and tocotrienols,
      carotenoids, and phenolic compounds are largely distributed in plant products.
      Most of them are not synthesized by human and need to be introduced with diet
      according to the Recommended Daily Intake (RDI). This work was aimed to give a
      comprehensive overview on the occurrence of these antioxidants in plants, in
      particular in plant foods, on the mechanisms of biosynthesis, and on conventional
      (liquid-liquid or solid-liquid extraction, Soxhlet) and innovative (enzymatic
      assisted, pressurized fluid, supercritical fluid, ultrasound-assisted, microwave
      assisted, pulsed electric field) extraction systems. 

PMID- 25751788
TI  - Are food compounds able to modulate noxious activities induced by cadmium
      exposure?
AB  - Cadmium is one of the most toxic environmental and industrial pollutants and is
      able to induce severe injury because it is poorly excreted, accumulating in
      various organs. This common pollutant is responsible for serious damage in lung,
      brain, testis, kidney, liver, circulatory system, and bone. Food compounds, such
      as flavonoids, represent the most abundant polyphenols in human diet and comprise
      thousands of substances, which are freely available as high-dose dietary
      supplements. The mechanism of action of these ones consists in free radical
      scavenging and metal sequestration. The interaction of metal ions with flavonoids
      leads to chelation and the use of these natural compounds is better than the
      synthetic ones due to their lower toxic effects. The aim of this review is to
      describe the role of some food compounds, focusing on flavonoids for modulating
      noxious biological activities induced by cadmium exposure.

PMID- 25751789
TI  - The use of shear thickening nanocomposites in impact resistant materials.
AB  - The work presented here demonstrates using a novel, field-responsive
      nanocomposite based on shear thickening fluids (STFs) as responsive protective
      materials with superior damping and energy adsorption properties. Peak forces and
      accelerations measured using an instrumented Instron drop tower demonstrate that
      STF nanocomposite prototypes and impact foam taken from a commercial football
      helmet have similar performance for low kinetic energy impacts. However, tests
      with STF nanocomposite samples exhibit significantly reduced peak acceleration
      and peak force for impacts above 15 J. Thus, the STF containing nanocomposite
      material provides improved energy adsorption upon impact as compared to the
      commercial foam. These tests suggest that STF nanocomposite materials have
      promising potential as novel energy dissipating components in personal protective
      equipment.

PMID- 25751790
TI  - Origin of pressure-induced crystallization of Ce75Al25 metallic glass.
AB  - Phase transitions in amorphous alloys under pressure are an important fundamental
      problem. Here we report on a first-principles study that reproduces the recently
      discovered pressure-induced crystallization of amorphous Ce100-xAlx (x<25) alloys
      and reveals an atomistic transformation mechanism. Contrary to common belief,
      pressure-induced devitrification of an amorphous Ce-Al alloy is not due to the Ce
      4f delocalization that is expected to bring the size of Ce atoms closer to that
      of Al atoms. Our theoretical results show that the Bader volume of Ce is always
      larger than that of Al. A continuous increase in the relative Ce/Al Bader volume
      leads to favourable conditions for forming a close-packed structure at high
      pressure. The results also show that the Hume-Rothery rules are not applicable to
      describe the structures of substitutional alloys at high pressure. This study
      provides a new perspective on the electron distribution in lanthanide alloys
      under the application of pressure. 

PMID- 25751791
TI  - Colonic polyps in lynch syndrome.

PMID- 25751792
TI  - Risk stratification of pT1 colorectal tumors based on histopathological analysis:
      read at your own risk.

PMID- 25751793
TI  - Clinical practice guidelines for ostomy surgery.

PMID- 25751794
TI  - Defining the adenoma burden in lynch syndrome.
AB  - BACKGROUND: Patients with 10 or more lifetime adenomas are candidates for genetic
      counseling and testing for polyposis syndromes. Lynch syndrome falls under the
      umbrella of hereditary nonpolyposis colorectal cancer, and it is assumed that
      patients with Lynch syndrome do not develop multiple adenomas. OBJECTIVE: The
      objective of this study was to document the number of adenomas in patients with
      Lynch syndrome. DESIGN: This was a retrospective review of clinical, colonoscopy,
      and pathology records of patients with Lynch syndrome in a prospectively
      maintained hereditary colorectal cancer database. SETTINGS: The study was
      conducted at a single-institution tertiary care center with specialized practice
      in hereditary colorectal cancer syndromes. PATIENTS: We included 263 patients
      with a germline mutation in 1 of the 4 DNA mismatch repair genes. INTERVENTIONS:
      Colonoscopy and polypectomy were the study interventions. MAIN OUTCOME MEASURES:
      The lifetime cumulative number of colorectal adenomas and their characteristics
      were measured. RESULTS: A total of 107 of the 263 patients had 1 or more
      adenomas. Sixty-one patients had 1 adenoma, 29 (11%) had 2 to 5 adenomas, 6 (2%)
      had 6 to 9 adenomas, and 11 patients (4%) had 10 or more cumulative adenomas. The
      maximum number of synchronous adenomas in any individual was 22, and the maximum
      number of cumulative adenomas in any individual was 24. Twenty-four of the 107
      patients with adenomas underwent a total colectomy or proctocolectomy and were
      excluded from long-term follow-up. In the remaining 83 patients with adenomas,
      426 colonoscopies were performed. A total of 220 (54%) were normal or had
      hyperplastic polyps; 313 adenomas were found in 206 examinations (46%), and 123
      (39%) of the adenomas were advanced. LIMITATIONS: There was variability in the
      interval of colonoscopy surveillance. Some patients had a variant of unknown
      significance and were separated from those with a deleterious mutation.
      CONCLUSIONS: Although 10 or more adenomas prompt testing for polyposis syndromes,
      Lynch syndrome should also be considered in the differential diagnosis.

PMID- 25751795
TI  - Area of submucosal invasion and width of invasion predicts lymph node metastasis
      in pT1 colorectal cancers.
AB  - BACKGROUND: The prediction of lymph node metastasis by current histopathological
      methods is imprecise. OBJECTIVE: The aim of this study was to evaluate currently
      used and possible new high-risk features associated with lymph node metastasis to
      identify the markers of lymph node metastasis. DESIGN/PATIENT/SETTING: Two
      hundred seven pT1 cancers were identified through the Northern and Yorkshire
      Cancer Registry and Information Services database and digitally scanned.
      Phenotypic and quantitative features of the pT1 cancers were evaluated. Lymph
      node metastasis and high-risk feature status were obtained through pathology
      reports of resections, and high-risk phenotypic features were identified.
      RESULTS: Lymph node metastasis was noted in 19 patients (9.2%). pT1 cancers with
      lymph node metastasis had a significantly wider area of invasion (p = 0.001) and
      greater area of submucosal invasion (p < 0.001) compared with pT1 cancers without
      lymph node metastasis. Qualitative features such as grade of differentiation and
      vascular and lymphatic invasion were significant predictors of lymph node
      metastasis (p < 0.0001, p = 0.039, and p = 0.018). Modified receiver-operating
      characteristics curves generated cutoff values of 11.5 mm for the width of
      invasion and 35 mm(2) for the area of submucosal invasion. When tested separately
      with other qualitative factors on multivariate analysis, both width greater than
      11.5 mm (OR, 12.12; 95% CI, 2.19-67.23; p = 0.004) and area of submucosal
      invasion greater than 35 mm(2) (OR, 22.44; 95% CI, 2.7-186.63; p = 0.004) was
      predictive of lymph node metastasis. LIMITATIONS: This is a retrospective study
      and is limited by its small sample size. CONCLUSION: This study has shown that
      the width and area of submucosal invasion are potential predictors of lymph node
      metastasis and superior to the depth of invasion. Together with the other
      qualitative phenotypic features, these quantitative factors could be used to
      decide the most appropriate treatment for pT1 cancers.

PMID- 25751796
TI  - Early removal of urinary catheters after rectal surgery is associated with
      increased urinary retention.
AB  - BACKGROUND: Urinary retention after rectal resection is common and managed
      prophylactically by prolonging urinary catheterization. However, because
      indwelling urinary catheterization is a well-established risk factor for urinary
      tract infection, the ideal timing for urinary catheter removal following a rectal
      resection is unknown. OBJECTIVE: We hypothesized that early urinary catheter
      removal (on or before postoperative day 2) would be associated with urinary
      retention. DESIGN: This study is a retrospective review of medical records.
      SETTING: This study was conducted at a colorectal surgery service at a tertiary
      care academic teaching hospital. PATIENTS: Adults undergoing rectal resection
      operations by colorectal surgeons in 2005 to 2010 were selected. MAIN OUTCOME
      MEASURE: The primary outcome measured was urinary retention. RESULTS: Of 205
      patients included, 41 (20%) developed urinary retention. Male sex (OR, 3.9; 95%
      CI, 1.7-9), increased intraoperative intravenous fluid (OR for each liter, 1.2;
      95% CI, 1.04-1.48), and urinary catheter removal on postoperative day 2 or
      earlier (OR, 3.8; 95% CI, 1.4-10.5) were associated with urinary retention on
      multivariable analysis. Early catheter removal was not associated with decreased
      urinary tract infection rates (p = 0.29) but was associated with shorter length
      of stay (6.5 vs 8.9 days; p = 0.005). LIMITATIONS: The retrospective nature of
      this study did not allow for a precise definition of urinary retention.
      Preoperative urinary function was not available, and the patient sample was
      heterogeneous, including several indications for rectal resection. Urinary
      catheters were not removed per protocol and therefore subject to bias. The study
      is likely underpowered to detect differences in urinary tract infection between
      urinary catheter removal groups. CONCLUSION: In patients undergoing rectal
      resection, we found that urinary catheter removal on or before postoperative day
      2 was associated with urinary retention (see Video, Supplemental Digital Content
      1, http://links.lww.com/DCR/A172).

PMID- 25751797
TI  - Size and distribution of lymph nodes in rectal cancer resection specimens.
AB  - BACKGROUND: The detection of lymph node involvement is fundamental to the staging
      of rectal cancer, and aids in prognostication and identification of patients who
      will benefit from adjuvant therapy. The anatomical variation in distribution and
      size of mesorectal lymph nodes has received scant attention. OBJECTIVE: This
      study aimed to determine the size and distribution of lymph nodes in rectal
      cancer resection specimens. DESIGN: This was a prospective, observational study
      of rectal cancer resection specimens analyzed by a single histopathologist.
      SETTING: This study was conducted from January 2007 to July 2013 at the authors'
      institution. PATIENTS: Two hundred forty-four consecutive patients underwent
      resection for rectal cancer. MAIN OUTCOME MEASURES: The size and distribution of
      lymph nodes in the resection specimens and the anatomical position of mesorectal
      lymph nodes in relation to the peritoneal reflection, tumor, and anal verge were
      recorded. RESULTS: A total of 10,473 lymph nodes were retrieved in 244 patients
      (75 women; median age, 68 years (interquartile range, 59-75 years)). One hundred
      seventy-three anterior resection and 71 abdominoperineal resection specimens were
      analyzed. Median lymph node yield was 41 lymph nodes (interquartile range, 31
      52); 344 of 10,473 (3.2%) lymph nodes were positive. Lymph nodes were distributed
      in the mesorectum, sigmoid mesentery, and vascular pedicle in 40%, 32%, and 28%
      of the patients. Sixty-eight percent of mesorectal lymph nodes were above the
      peritoneal reflection. Mesorectal lymph node distribution in relation to the
      tumor was 53% above, 36% adjacent to, and only 11% below the tumor. Ninety-five
      of 334 (28%) positive nodes were <=3 mm in diameter. LIMITATIONS: Resection
      specimens analyzed by other pathologists (<5%) have not been included, and fat
      clearance techniques were not used to retrieve lymph nodes. CONCLUSIONS: To
      ensure accurate nodal staging of rectal cancer, both resection and subsequent
      pathological evaluation should focus on the mesorectum in close proximity to the
      tumor and along the superior rectal artery. Small lymph nodes (<3 mm in size)
      should not be overlooked, and lymph node metastasis to the sigmoid mesentery is
      rare (see Video, Supplemental Digital Content 1, http://links.lww.com/DCR/A177).

PMID- 25751798
TI  - Does patient rurality predict quality colon cancer care?: A population-based
      study.
AB  - BACKGROUND: More than 50 million people reside in rural America. However, the
      impact of patient rurality on colon cancer care has been incompletely
      characterized, despite its known impact on screening. OBJECTIVE: Our study sought
      to examine the impact of patient rurality on quality and comprehensive colon
      cancer care. DESIGN: We constructed a retrospective cohort of 123,129 patients
      with stage 0 to IV colon cancer. Rural residence was established based on the
      patient medical service study area designated by the registry. SETTINGS: The
      study was conducted using the 1996-2008 California Cancer Registry. PATIENTS: All
      of the patients diagnosed between 1996 and 2008 with tumors located in the colon
      were eligible for inclusion in this study. MAIN OUTCOME MEASURES: Baseline
      characteristics were compared by rurality status. Multivariate regression models
      then were used to examine the impact of rurality on stage in the entire cohort,
      adequate lymphadenectomy in stage I to III disease, and receipt of chemotherapy
      for stage III disease. Proportional-hazards regression was used to examine the
      impact of rurality on cancer-specific survival. RESULTS: Of all of the patients
      diagnosed with colon cancer, 18,735 (15%) resided in rural areas. Our
      multivariate models demonstrate that rurality was associated with later stage of
      diagnosis, inadequate lymphadenectomy in stage I to III disease, and lower
      likelihood of receiving chemotherapy for stage III disease. In addition, rurality
      was associated with worse cancer-specific survival. LIMITATIONS: We could not
      account for socioeconomic status directly, although we used insurance status as a
      surrogate. Furthermore, we did not have access to treatment location or distance
      traveled. We also could not account for provider or hospital case volume, patient
      comorbidities, or complications. CONCLUSIONS: A significant portion of patients
      treated for colon cancer live in rural areas. Yet, rural residence is associated
      with modest differences in stage, adherence to quality measures, and survival.
      Future endeavors should help improve care to this vulnerable population (see
      video, Supplemental Digital Content 1, http://links.lww.com/DCR/A143).

PMID- 25751799
TI  - Prediction of need for surgery after endoscopic balloon dilation of ileocolic
      anastomotic stricture in patients with Crohn's disease.
AB  - BACKGROUND: Endoscopic balloon dilation is used to treat ileocolic anastomotic
      stricture attributed to recurrent Crohn's disease. OBJECTIVE: The purpose of this
      work was to investigate long-term outcomes after dilation of ileocolic
      anastomotic stricture and to identify risk factors associated with the need for
      subsequent surgical intervention. DESIGN: This was a retrospective study based on
      chart review of an electronic medical chart system. SETTINGS: The study was
      conducted at a tertiary care center. PATIENTS: All of the eligible patients with
      ileocolic anastomotic stricture attributed to recurrent Crohn's disease treated
      with endoscopic dilation between December 1998 and May 2013 were evaluated.
      Patients with concurrent enterocutaneous fistula or abdominal or pelvic abscess
      were excluded. MAIN OUTCOME MEASURES: The main outcome measure was the need for
      subsequent salvage surgery because of stricture-related symptoms. RESULTS: A
      total of 185 patients with Crohn's disease (45.9% women; mean age, 43.1 years;
      symptomatic strictures in 80%) underwent 462 endoscopic dilations of ileocolic
      anastomosis (median per-patient dilations, 2; range, 1-3). During a mean follow
      up of 3.9 years, 27 patients (14.6%) required hospitalization without surgery for
      stricture-related symptoms, and 66 patients (35.7%) required subsequent salvage
      surgery. Specific medical management, type of anastomosis, and endoscopic
      intralesional steroid injection had no impact on the risk of needing surgery.
      Significant factors associated with the need for surgery on multivariable
      analysis were symptomatic disease (HR, 3.54 [95% CI, 1.41-8.93]), longer time
      interval from last surgery (HR, 1.05 [95% CI, 1.01-1.10]), and radiographic
      proximal bowel dilation (HR, 2.36 [95% CI, 1.38-4.03]). A nomogram estimating the
      need for surgery was created with a concordance index of 0.67. LIMITATIONS: The
      study was limited by its retrospective design. CONCLUSIONS: Although endoscopic
      dilation is a valid option for ileocolic anastomotic stricture attributed to
      recurrent Crohn's disease, the need for surgery is common. The nomogram can
      identify patients who might benefit from upfront surgery.

PMID- 25751800
TI  - Do the advantages of a minimally invasive approach remain in complex colorectal
      procedures? A nationwide comparison.
AB  - BACKGROUND: Since the introduction of laparoscopic colectomy, experience and
      technology continue to improve. Although accepted for many colorectal conditions,
      its use and outcomes in complex procedures are less understood. OBJECTIVE: The
      purpose of this work was to compare the perioperative outcomes of laparoscopic
      transverse colectomy and total abdominal colectomy (study group) with an open
      approach (comparative group) and the more established laparoscopic right, left,
      and sigmoid colectomies (control group). DESIGN: This was a retrospective review
      of the Nationwide Inpatient Sample (2008-2011) of all patients undergoing
      elective right, left, sigmoid, total, or transverse colectomy as identified by
      International Classification of Diseases, Ninth Revision, Clinical Modification
      procedure codes. Risk-adjusted 30-day outcomes were assessed using regression
      modeling accounting for patient characteristics, comorbidities, and surgical
      procedures. SETTINGS: The study included a national sample from a population
      database. PATIENTS: There were 45,771 admissions: 2946 in the study group, 36,949
      in the control group, and 5876 in the open comparative group. MAIN OUTCOME
      MEASURES: Mortality was the primary outcome. Secondary outcomes included in
      hospital complications, length of stay, and hospital charges. RESULTS: The
      patients were predominantly white (73%), had private insurance (64%), and
      underwent surgery at urban centers (92%). Mortality was similar between the study
      and control groups (0.42% vs 0.51%; p = 0.52), with a higher complication rate in
      the study group (19% vs 14%; p < 0.01). The study group was also associated with
      a lower mortality rate compared with the open group (0.51% vs 2.20%; p < 0.01),
      which remained consistent after adjusting for covariates (OR, 0.38 [95% CI, 0.20
      0.71]; p < 0.01). The study group had fewer complications overall compared with
      the open group (19% vs 27%; p < 0.01) and a shorter median length of stay (4.6 vs
      6.3 days; p < 0.01). LIMITATIONS: This was a retrospective study using an
      administrative database. CONCLUSIONS: A laparoscopic approach for total abdominal
      and transverse colectomies has similar mortality rates and slightly higher
      complications than the more established laparoscopic colectomy procedures and
      improved perioperative outcomes when compared with an open technique (see Video,
      Supplemental Digital Content 1, http://links.lww.com/DCR/A178).

PMID- 25751801
TI  - Desmoids and genotype in familial adenomatous polyposis.
AB  - BACKGROUND: Desmoid disease can be a serious, life-threatening complication of
      familial adenomatous polyposis. The ability to predict patients at increased
      desmoid risk is important, but a convincing genotype-phenotype correlation for
      desmoid formation has not yet been described. PURPOSE: The aim of this study is
      to assess the relationship between desmoid disease and genotype in patients with
      familial adenomatous polyposis. DESIGN: This is a cohort study. PATIENTS: All
      patients with familial adenomatous polyposis and a documented pathogenic APC
      mutation in themselves or a first-degree relative were selected. MAIN OUTCOMES
      MEASURES: The comparison of genotype and the presence, stage, and site of desmoid
      disease are the primary end points of this study. RESULTS: Three hundred twenty
      three patients from 219 families were identified. Mutations spanned the length of
      the gene, from codon 213 to codon 2051. Desmoid disease was diagnosed in 77
      patients from 68 families. Desmoid disease was found in 14.9% of patients with a
      mutation 5' of codon 400, 23.2% of patients with a mutation from codon 401 to
      1400, and in 37.1% of those with a mutation 3' of 1400. All patients with 5'
      mutations had stage I or II abdominal desmoid disease, and all tumors were stable
      or shrinking. Twelve percent of patients who had desmoid disease with mutations
      between codons 400 and 1400 had stage III or IV desmoid disease, and 5 of 42
      (12%) tumors were growing at the time of the study. There had been 2 desmoid
      related deaths. Almost half (44%) of patients who had desmoid disease with
      mutations 3' of codon 1400 had stage III or IV disease. Three of 14 tumors were
      growing (21%), and there were 4 desmoid-related deaths. LIMITATIONS: This study
      was conducted at a tertiary referral center, and there was no systematic
      surveillance for desmoids. CONCLUSION: Desmoid disease occurs in patients who
      have familial adenomatous polyposis with almost any APC mutation, although there
      is an increased propensity in those with a 3' mutation. The incidence and
      severity of the desmoid disease are related to the site of the mutation.

PMID- 25751802
TI  - Laparoscopic ventral rectopexy for rectoanal intussusception: postoperative
      evaluation with proctography.
AB  - BACKGROUND: Laparoscopic ventral rectopexy can relieve symptoms of obstructed
      defecation and fecal incontinence in patients with rectoanal intussusception.
      However, pelvic floor imaging after surgery has not been reported. OBJECTIVE:
      This study was designed to assess the outcome of patients who underwent
      laparoscopic ventral rectopexy for rectoanal intussusception, with special
      reference to the postoperative findings on evacuation proctography. DESIGN: This
      study was a retrospective analysis of prospectively collected data. SETTING: The
      study was conducted from 2012 to 2013 at the Department of Surgery, Kameda
      Medical Center, Japan. PATIENTS: We included 26 patients with symptomatic
      rectoanal intussusception. INTERVENTION: Laparoscopic ventral rectopexy was
      performed. MAIN OUTCOME MEASURE: Evacuation proctography was performed before and
      6 months after the procedure. Defecatory function was evaluated using the
      Constipation Scoring System and Fecal Incontinence Severity Index. RESULTS: Of 26
      patients with rectoanal intussusception preoperatively, 22 had symptoms of
      obstructed defecation and 21 complained of fecal incontinence. Postoperatively,
      rectoanal intussusception was eliminated in all patients, though 8 developed
      recto rectal intussusception. There was an overall reduction in both grade 2
      rectocele size (median preop 26 mm vs. postop 11 mm; p < 0.0001) and pelvic floor
      descent (median preop 26 mm vs. postop 20 mm; p < 0.0001). 6 months after
      surgery, a reduction of at least 50% was observed in the Constipation Scoring
      System score for 9 patients (41%) with obstructive defecation and in the Fecal
      Incontinence Severity Index score for 14 incontinent patients (67%). LIMITATIONS:
      This was a preliminary study with a small sample size, no control group, and
      short follow-up time. CONCLUSION: Evacuation proctography showed anatomical
      correction in patients with rectoanal intussusception who underwent laparoscopic
      ventral rectopexy. However, the data also indicate that such correction does not
      necessarily result in meaningful symptomatic relief.

PMID- 25751804
TI  - Quality-of-life assessment in children with fecal incontinence.
AB  - BACKGROUND: Fecal incontinence is a clinical condition that causes embarrassment
      and changes the perception of quality of life. The absence of a specific tool for
      assessing fecal incontinence in children led us to adapt an instrument originally
      developed for adults, which has already been validated into Portuguese.
      OBJECTIVE: The purpose of this work was to evaluate the quality of life of
      children with fecal incontinence. DESIGN: This is a single-center, prospective
      study based on the application of survey. The Fecal Incontinence Quality of Life
      questionnaire was modified by eliminating 2 questions related to sexuality and by
      substituting the word "depressed" with "sad" in the statement, "I feel
      depressed." SETTING: The study took place at a tertiary academic medical center.
      PATIENTS: Forty-one children >5 years of age, with incontinence of organic
      etiology and preserved cognition but without stomy, were interviewed with the use
      of the Fecal Incontinence Quality of Life modified questionnaire. To evaluate the
      discrimination validity, 28 healthy children were interviewed as control
      subjects. MAIN OUTCOME MEASURES: As to reproducibility, a test/retest was
      performed, involving 25 children. For construct validation, the Fecal
      Incontinence Quality of Life modified was correlated with the generic instrument
      Autoquestionnaire Qualite de Vie Enfant Image with the continence index Sao Paulo
      Score of Continence. RESULTS: The average values by scale included lifestyle,
      3.1; emotional, 2.8; behavior, 2.3; and embarrassment, 1.6. The average values
      for the control group included lifestyle, 3.7; emotional, 4.0; behavior, 3.6; and
      embarrassment, 3.6. The instrument showed a general reliability of 0.78, measured
      by the Cronbach alpha. Reproducibility was also >0.90 according to the Cronbach
      alpha. LIMITATIONS: The intrinsic characteristics of children include their
      constant growth, and this presented a challenge in our search for an instrument
      that permitted us to identify and measure these variations. CONCLUSIONS: The
      experiment showed a reduction in all of the scale values, particularly for
      embarrassment in children with fecal incontinence.

PMID- 25751805
TI  - Perineal proctectomy with bio-thiersch procedure for complete rectal prolapse
      with fecal incontinence.

PMID- 25751803
TI  - Clinical outcome and efficacy of antegrade colonic enemas administered via an
      indwelling cecostomy catheter in adults with defecatory disorders.
AB  - BACKGROUND: Antegrade colonic enemas are used in selected adult patients with
      defecatory disorders. Conduit stenosis requiring revisional surgery is common.
      OBJECTIVE: The aim of the study was to determine whether stenosis could be
      avoided by using an indwelling antegrade continence enema catheter in an
      appendiceal or cecal conduit, and to describe medium-term clinical outcomes.
      DESIGN: This study was a retrospective case series. SETTING: The study was
      conducted at a tertiary referral hospital in Sydney, Australia. PATIENTS: Adults
      administering antegrade colonic enemas to manage defecatory disorders were
      selected for the study. METHODS: Patients with an indwelling antegrade continence
      enema catheter completed a face-to-face survey when they attended the clinic for
      catheter change. A postal survey was sent to nonattenders, and, if it was not
      returned, the patient was contacted, and the survey was completed by telephone.
      The survey asked about irrigation techniques, satisfaction, confidence to manage,
      and continence, using quantitative scores. RESULTS: Fifty-four patients (45
      female; mean age, 49 years) had constipation (n = 31), incontinence (n = 6), both
      incontinence and constipation (n = 2) or obstructed defecation due to gracilis
      neosphincter (n = 5), congenital anomalies (n = 8), or spinal injuries (n = 2).
      Thirty-five patients (65%) continued to irrigate for a mean follow-up of 5.5
      years (range, 4 months to 13.7 years). Mean enema volume was 1178 mL (95% CI, 998
      1357; range, 350-2000 mL), and half the patients added a stimulant to the
      irrigation. Mean total toileting time was 59 minutes (95% CI, 48-66; range, 15
      120 minutes). Twenty-one patients had incontinence between irrigations, and in
      17% incontinence was severe (St. Mark score >12). Satisfaction (visual analogue
      scale = 8.1) and confidence to partake in social activities (visual analogue
      scale = 8.2) and all-day activities (visual analogue scale = 7.1) were high.
      Complications included superficial wound infection (n = 15), wound infection
      requiring surgery (n = 6), paraconduit hernia (n = 2), and indwelling antegrade
      continence enema catheter dislodgement (n = 33). There was no conduit track
      stenosis. LIMITATIONS: The study is a medium-term retrospective case series using
      patient-reported outcomes and clinical records without a control group.
      CONCLUSIONS: With the use of the indwelling antegrade continence enema catheter,
      appendicostomy and cecostomy stenosis requiring revisional surgery was avoided.
      Antegrade colonic irrigation failed in about one-third of cases; in the 65% who
      continued to irrigate, satisfactory functional outcome was achieved.

PMID- 25751806
TI  - Mesh pouch pexy in the management of J-pouch prolapse.
AB  - J-pouch prolapse is a rare complication after IPAA. To date, limited data exist
      regarding management of this condition, with most reported cases involving suture
      pouch pexy. We present our experience and technique with 3 patients who were
      treated with transabdominal mesh pexy repair. 

PMID- 25751808
TI  - Errors, omissions, and publication bias.

PMID- 25751807
TI  - Circumferential anal giant condyloma acuminatum: a new surgical approach.
AB  - INTRODUCTION: Perianal giant condyloma acuminatum is a rare clinical condition
      related to human papillomavirus infection and characterized by a circumferential,
      exophytic, cauliflower-like mass with an irregular warty surface localized in the
      anal region. TECHNIQUE: A circular incision with a diathermocoagulator was
      performed on macroscopically healthy skin, 1 cm from the margin of the lesion.
      The dermis was divided from the subcutaneous tissue. This way, a mucocutaneous
      cylinder including the whole lesion was obtained. A median radial incision was
      carried out to open the cylinder at its front. A progressive circumferential
      section on healthy mucosa (~1 cm above the margin of the lesion) by means of a
      radiofrequency dissector allowed for the complete removal of the mass. The
      healthy mucosa of the anal canal was pulled out by Allis forceps and was sutured
      to the external margin of the internal sphincter with single layer of Vicryl
      (polyglactin 910) 2-0 sutures. RESULTS: Two months after surgery, no findings of
      anal stenosis or mucosal ectropion were reported. At the 1-year follow-up there
      was no recurrence of condylomatosis in any of the 3 cases. CONCLUSIONS: Our
      procedure seems simpler to perform when compared with other techniques and
      reduces hospital stay and complications such as anal stenosis and mucosal
      ectropion.

PMID- 25751809
TI  - The authors reply.

PMID- 25751810
TI  - Effectiveness of efferent loop stimulation: looking for a suitable protocol.

PMID- 25751811
TI  - The authors reply.

PMID- 25751815
TI  - A high-throughput chemical screen reveals that harmine-mediated inhibition of
      DYRK1A increases human pancreatic beta cell replication.
AB  - Types 1 and 2 diabetes affect some 380 million people worldwide. Both ultimately
      result from a deficiency of functional pancreatic insulin-producing beta cells.
      Beta cells proliferate in humans during a brief temporal window beginning around
      the time of birth, with a peak percentage (~2%) engaged in the cell cycle in the
      first year of life. In embryonic life and after early childhood, beta cell
      replication is barely detectable. Whereas beta cell expansion seems an obvious
      therapeutic approach to beta cell deficiency, adult human beta cells have proven
      recalcitrant to such efforts. Hence, there remains an urgent need for
      antidiabetic therapeutic agents that can induce regeneration and expansion of
      adult human beta cells in vivo or ex vivo. Here, using a high-throughput small
      molecule screen (HTS), we find that analogs of the small molecule harmine
      function as a new class of human beta cell mitogenic compounds. We also define
      dual-specificity tyrosine-regulated kinase-1a (DYRK1A) as the likely target of
      harmine and the nuclear factors of activated T cells (NFAT) family of
      transcription factors as likely mediators of human beta cell proliferation and
      differentiation. Using three different mouse and human islet in vivo-based
      models, we show that harmine is able to induce beta cell proliferation, increase
      islet mass and improve glycemic control. These observations suggest that harmine
      analogs may have unique therapeutic promise for human diabetes therapy. Enhancing
      the potency and beta cell specificity of these compounds are important future
      challenges. 

PMID- 25751818
TI  - Takotsubo cardiomyopathy: how T waves behave under stress.

PMID- 25751816
TI  - RIFINs are adhesins implicated in severe Plasmodium falciparum malaria.
AB  - Rosetting is a virulent Plasmodium falciparum phenomenon associated with severe
      malaria. Here we demonstrate that P. falciparum-encoded repetitive interspersed
      families of polypeptides (RIFINs) are expressed on the surface of infected red
      blood cells (iRBCs), where they bind to RBCs--preferentially of blood group A--to
      form large rosettes and mediate microvascular binding of iRBCs. We suggest that
      RIFINs have a fundamental role in the development of severe malaria and thereby
      contribute to the varying global distribution of ABO blood groups in the human
      population.

PMID- 25751819
TI  - Development and evaluation of a home enteral nutrition team.
AB  - The organisation of services to support the increasing number of people receiving
      enteral tube feeding (ETF) at home varies across regions. There is evidence that
      multi-disciplinary primary care teams focussed on home enteral nutrition (HEN)
      can provide cost-effective care. This paper describes the development and
      evaluation of a HEN Team in one UK city. A HEN Team comprising dietetians, nurses
      and a speech and language therapist was developed with the aim of delivering a
      quality service for people with gastrostomy tubes living at home. Team objectives
      were set and an underpinning framework of organisation developed including a care
      pathway and a schedule of training. Impact on patient outcomes was assessed in a
      pre-post test evaluation design. Patients and carers reported improved support in
      managing their ETF. Cost savings were realised through: (1) prevention of
      hospital admission and related transport for ETF related issues; (2) effective
      management and reduction of waste of feed and thickener; (3) balloon gastrostomy
      tube replacement by the HEN Team in the patient's home, and optimisation of
      nutritional status. This service evaluation demonstrated that the establishment
      of a dedicated multi-professional HEN Team focussed on achievement of key
      objectives improved patient experience and, although calculation of cost savings
      were estimates, provided evidence of cost-effectiveness. 

PMID- 25751822
TI  - Erratum for Assessing sustainability of InSHAPE participants' fitness activities
      in a community mental health setting.

PMID- 25751823
TI  - Is satiety (lack thereof) the culprit with obesity?

PMID- 25751820
TI  - Nutrition and respiratory health--feature review.
AB  - Diet and nutrition may be important modifiable risk factors for the development,
      progression and management of obstructive lung diseases such as asthma and
      chronic obstructive pulmonary disease (COPD). This review examines the
      relationship between dietary patterns, nutrient intake and weight status in
      obstructive lung diseases, at different life stages, from in-utero influences
      through childhood and into adulthood. In vitro and animal studies suggest
      important roles for various nutrients, some of which are supported by
      epidemiological studies. However, few well-designed human intervention trials are
      available to definitively assess the efficacy of different approaches to
      nutritional management of respiratory diseases. Evidence for the impact of higher
      intakes of fruit and vegetables is amongst the strongest, yet other dietary
      nutrients and dietary patterns require evidence from human clinical studies
      before conclusions can be made about their effectiveness. 

PMID- 25751817
TI  - Myocardial healing requires Reg3beta-dependent accumulation of macrophages in the
      ischemic heart.
AB  - Cardiac healing after myocardial ischemia depends on the recruitment and local
      expansion of myeloid cells, particularly macrophages. Here we identify Reg3beta
      as an essential regulator of macrophage trafficking to the damaged heart. Using
      mass spectrometry-based secretome analysis, we found that dedifferentiating
      cardiomyocytes release Reg3beta in response to the cytokine OSM, which signals
      through Jak1 and Stat3. Loss of Reg3beta led to a large decrease in the number of
      macrophages in the ischemic heart, accompanied by increased ventricular
      dilatation and insufficient removal of neutrophils. This defect in neutrophil
      removal in turn caused enhanced matrix degradation, delayed collagen deposition
      and increased susceptibility to cardiac rupture. Our data indicate that OSM,
      acting through distinct intracellular pathways, regulates both cardiomyocyte
      dedifferentiation and cardiomyocyte-dependent regulation of macrophage
      trafficking. Release of OSM from infiltrating neutrophils and macrophages
      initiates a positive feedback loop in which OSM-induced production of Reg3beta in
      cardiomyocytes attracts additional OSM-secreting macrophages. The activity of the
      feedback loop controls the degree of macrophage accumulation in the heart, which
      is instrumental in myocardial healing. 

PMID- 25751821
TI  - Fish oil decreases hepatic lipogenic genes in rats fasted and refed on a high
      fructose diet.
AB  - Fasting and then refeeding on a high-carbohydrate diet increases serum and
      hepatic triacylglycerol (TAG) concentrations compared to standard diets. Fructose
      is a lipogenic monosaccharide which stimulates de novo fatty acid synthesis.
      Omega-3 (n-3) fatty acids stimulate hepatic beta-oxidation, partitioning fatty
      acids away from TAG synthesis. This study investigated whether dietary n-3 fatty
      acids from fish oil (FO) improve the hepatic lipid metabolic response seen in
      rats fasted and then refed on a high-fructose diet. During the post-prandial
      (fed) period, rats fed a FO rich diet showed an increase in hepatic peroxisome
      proliferator-activated receptor alpha (PPAR-alpha) gene expression and decreased
      expression of carbohydrate responsive element binding protein (ChREBP), fatty
      acid synthase (FAS) and microsomal triglyceride transfer protein (MTTP). Feeding
      a FO rich diet for 7 days prior to 48 h of fasting resulted in lower hepatic TAG,
      lower PPAR-alpha expression and maintenance of hepatic n-3 fatty acid content.
      Refeeding on a high fructose diet promoted an increase in hepatic and serum TAG
      and in hepatic PPAR-alpha, ChREBP and MTTP expression. FO did not prevent the
      increase in serum and hepatic TAG after fructose refeeding, but did decrease
      hepatic expression of lipogenic genes and increased the n-3 fatty acid content of
      the liver. n-3 Fatty acids can modify some components of the hepatic lipid
      metabolic response to later feeding with a high fructose diet. 

PMID- 25751824
TI  - Aspergillus, angiogenesis, and obesity: the story behind beloranib.
AB  - Fumagillin, an antimicrobial compound first isolated in 1949 from the fungus
      Aspergillus fumigatus, four decades later was unexpectedly found to inhibit
      angiogenesis. Interest in developing angiogenesis inhibitor drugs as possible
      treatments for cancer led to the synthesis of analogs of fumagillin. Preclinical
      studies of various analog drugs confirmed that they inhibited angiogenesis, but
      they also were associated with weight loss as an adverse effect. Because adipose
      tissue can grow and regress throughout adulthood, is highly vascularized, and has
      angiogenic properties, interest in investigating anti-angiogenic agents in animal
      models of obesity found that fumagillin analogs caused dose-dependent reversible
      weight reduction and adipose tissue loss. Beloranib, a fumagillin analog that is
      an angiogenesis inhibitor and associated with decreased adiposity in animals, has
      been studied in phase I clinical trials for cancer. It is currently being
      investigated for the treatment of obesity and related conditions. Three phase I
      and three phase II studies found significant degrees of weight loss and
      acceptable tolerability for beloranib compared to placebo, justifying further
      clinical development of the drug for obesity.

PMID- 25751826
TI  - Nursing advocacy for women veterans and suicide.
AB  - Little is known about suicide variables in women Veterans. The authors reviewed
      numerous applicable health care and military literary sources regarding suicide
      in this population. The current article describes the surrounding circumstances,
      military war/conflict culture, and potential effects on women Veterans, including
      major collection problems with current Veteran data. Women Veterans are
      increasingly reporting more behavioral health issues (e.g., posttraumatic stress
      disorder) and attempting suicide upon civilian reintegration. Outcomes from this
      literature review suggest the importance of nursing advocacy to create better
      rapport and communication with women Veterans from Vietnam, Gulf I, Iraq, and
      Afghanistan wars seeking care at civilian health facilities, as some may present
      with suicidal ideologies.

PMID- 25751827
TI  - Understanding the perspectives of family members on telephone intervention for
      individuals with schizophrenia: results of a focus group.
AB  - The current study explored the perspectives of family members of individuals with
      schizophrenia to identify family needs. Six family members from the National
      Alliance on Mental Illness participated in a 90-minute focus group to share their
      perspectives on treatment needs and delivery options and to provide suggestions
      on needs that might be met using telephone-based treatment. Traditional
      atheoretical content analysis was performed. Five major themes emerged from the
      data: (a) isolation, (b) negative emotions, (c) recognition of illness, (d)
      communication with providers, and (e) problem solving. Findings indicate that
      families perceive needs that could potentially be met using telephone-based
      treatments. More research is needed to determine family responses to telephone
      based treatment initiatives.

PMID- 25751828
TI  - The Engagement Model for reducing seclusion and restraint: 13 years later.
AB  - In 2001, an inpatient psychiatric unit sought to greatly reduce, or even
      eliminate, the use of seclusion and restraint by initiating the Engagement Model.
      Despite many changes in management and staff, the model has remained largely
      intact and effective during the past 13 years. The current article reflects on
      key clinical interventions and leadership approaches that have helped sustain the
      culture change undertaken to better serve patients on this unit.

PMID- 25751831
TI  - Initial clinical results of a new telescopic IOL implanted in patients with dry
      age-related macular degeneration.
AB  - PURPOSE: To evaluate the safety and efficacy of the iol-AMD technology (London
      Eye Hospital Pharma, London, UK), which includes two injectable, hydrophobic
      acrylic intraocular lenses (IOLs) in a pilot study of patients diagnosed as
      having cataract and dry age-related macular degeneration. METHODS: The cataract
      surgery and IOL implantation were performed after a preoperative evaluation using
      the iolAMD simulator in eyes with bilateral intermediate dry age-related macular
      degeneration. Outcomes were intraoperative and postoperative complications,
      subjective and objective visual acuity improvement, visual field changes, and
      postoperative diplopia. RESULTS: Three eyes of 2 patients were evaluated. The
      surgeries were uneventful. All eyes gained monocular reading vision at the 1-week
      postoperative visit. One patient with monocular implantation recognized diplopia
      for distance vision. Preoperative corrected distance visual acuity ranged from
      20/800 to 20/125 and corrected near visual acuity was 20/800 or less. Two months
      after surgery, corrected distance and near visual acuities increased to levels
      between 20/40 and 20/25 (uncorrected distance visual acuity was 20/60 to 20/32;
      uncorrected near visual acuity was 20/200 to 20/25). CONCLUSIONS: These early
      results showed that the iolAMD simulator is a promising technology improving near
      and distance visual acuity in eyes with intermediate dry macular degeneration.
      The prismatic IOL effect did not lead to diplopia when implanted bilaterally. The
      surgery was safely performed.

PMID- 25751830
TI  - Evaluation of the mechanical properties of the anterior lens capsule following
      femtosecond laser capsulotomy at different pulse energy settings.
AB  - PURPOSE: To evaluate and compare the mechanical properties of anterior capsule
      opening performed with femtosecond laser capsulotomy at different energy settings
      in ex vivo porcine anterior lens capsule specimens. METHODS: Twenty-five fresh
      porcine eyes per group were included in the study. Femtosecond laser capsulotomy
      was performed with three different pulse energy levels: 2 uJ (low energy group),
      5 uJ (intermediate energy group), and 10 uJ (high energy group). The capsule
      openings were stretched with universal testing equipment until they ruptured. The
      morphologic profile of the cut capsule edges was evaluated using scanning
      electron microscopy. RESULTS: The high energy group had significantly lower
      rupture force (108 +/- 14 mN) compared to the intermediate energy group (118 +/-
      10 mN) (P < .05) and low energy group (119 +/- 11 mN) (P < .05), but the
      difference between the intermediate energy and low energy groups was not
      significant (P = .9479). The high energy group had significantly lower
      circumference stretching ratio (144% +/- 3%) compared to the intermediate energy
      group (148% +/- 3%) (P < .05) and low energy group (148% +/- 3%) (P < .05), but
      the difference between the intermediate energy group and low energy group was not
      significant (P = .9985). Scanning electron microscopy images showed that the edge
      was only serrated with low and intermediate energy, but additional signs of
      collagen melting and denaturation were observed at high energy. CONCLUSIONS:
      Anterior capsule openings created at a high energy level were slightly weaker and
      less extensible than those created at low or intermediate levels, possibly due to
      the increased thermal effect of photo-disruption.

PMID- 25751832
TI  - LASIK ablation centration: an objective digitized assessment and comparison
      between two generations of an excimer laser.
AB  - PURPOSE: To objectively define the effective centration of myopic femtosecond
      laser-assisted LASIK ablation pattern, evaluate the difference between achieved
      versus planned excimer laser ablation centration, and compare these results from
      two different generations of an excimer laser system. METHODS: The study
      retrospectively evaluated 280 eyes subjected to myopic LASIK. Digital image
      analysis was performed on Scheimpflug sagittal curvature maps (difference of
      preoperative to postoperative). Centration was assessed via proprietary software
      digital analysis of the coordinate displacement between the achieved ablation
      geometric center and the planned ablation center, which was the corneal vertex.
      Results from two different excimer laser generations (Eye-Q 400 [140 eyes] and
      EX500 [140 eyes]; Alcon/WaveLight, Fort Worth, TX) were compared. RESULTS: Radial
      displacement was on average 360 +/- 220 um (range: 0 to 1,030 um) in the Eye-Q
      400 laser group and 120 +/- 110 um (range: 0 to 580 um) in the EX500 laser group
      (P < .01). The percentage of eyes with displacement of greater than 300 um was
      52% in the Eye-Q 400 laser group and 4% in the EX500 laser group. CONCLUSIONS:
      Displacement of ablation pattern may depend on the laser platform used. The
      improvement in the efficiency of centration indicates that newer generation
      excimer lasers with faster eye tracking and active centration control appear to
      achieve a significantly more accurate centration of myopic ablation patterns. The
      authors propose this novel, objective technique for laser refractive surgeon
      evaluation may point out significant outcome measures not currently used in
      standard metrics of refractive laser efficiency.

PMID- 25751829
TI  - Femtosecond laser-assisted cataract surgery without OVD: a prospective
      intraindividual comparison.
AB  - PURPOSE: To compare femtosecond laser-assisted cataract surgery without the use
      of ophthalmic viscosurgical device (OVD) with standard phacoemulsification using
      OVD. METHODS: This was a prospective, randomized, single-center trial of 37
      patients (74 eyes) diagnosed as having significant cataract in both eyes.
      Randomly, one eye underwent standard phacoemulsification with OVD (the OVD
      group); this group acted as controls. The other eye was treated with the
      femtosecond laser; the subsequent manual part of the procedure was performed
      without OVD (non-OVD group). Time of surgery, amount of fluid used during
      phacoemulsification, central corneal thickness, intraocular pressure, endothelial
      cell count, and visual acuity were documented over the 6-month follow-up.
      RESULTS: There were no major complications and no significant difference in
      overall surgery time (non-OVD: 375 +/- 81 seconds; OVD: 362 +/- 43 seconds; P =
      .713) and in the quantity of fluid passing through the eye (non-OVD: 187 +/- 35
      mL; OVD: 186 +/- 27 mL; P = .952) between groups. Endothelial cell loss after 6
      months was not significantly different between groups (non-OVD: -2.4%; OVD: 
      2.7%; P = .880). Central corneal thickness was not different at 1 week
      postoperatively between groups (non-OVD: 575 +/- 45 um; OVD: 573 +/- 46 um; P =
      .820). Three patients in the OVD group and one patient in the non-OVD group
      experienced intraocular pressure greater than 25 mm Hg at 1 day postoperatively.
      There were no significant differences in corrected distance visual acuity between
      groups (logMAR non-OVD: 0.024; OVD: 0.038; P = .461). CONCLUSIONS: Femtosecond
      laser-assisted treatment allows the cataract surgeon to perform
      phacoemulsification and intraocular lens implantation without the use of OVD at
      no additional risk to the corneal endothelium. Furthermore, there was a tendency
      toward fewer increases in intraocular pressure in patients treated with the
      femtosecond laser.

PMID- 25751833
TI  - Day 1 wavefront aberrometry for prediction of refractive outcomes at year 1 in
      myopic LASIK.
AB  - PURPOSE: To determine amount of change in wavefront aberrometric measurements
      from 1 day to 1 year after myopic LASIK. METHODS: One hundred five eyes of 105
      patients underwent wavefront-guided LASIK. Objective wavefront aberrometric
      refractions were recorded preoperatively, at postoperative day 1, and at
      postoperative year 1. Subjective manifest refractions were also collected at
      postoperative year 1. RESULTS: When comparing objective wavefront aberrometric
      refractions at postoperative year 1 to postoperative day 1, there was a mean 0.33
      diopter spherical equivalent myopic shift. There was no significant difference in
      the number of eyes within 1.00 diopter of emmetropia spherical equivalent
      measured by wavefront aberrometric refraction at postoperative day 1 or year 1.
      There was a correlation of R(2) = 0.14 between degree of preoperative myopia and
      myopic shift. Higher-order aberrations were overall not increased at day 1 but
      increased significantly by year 1. Objective aberrometric refractions at
      postoperative day 1 can be useful in prediction of long-term refractive outcomes.
      CONCLUSIONS: There is a small myopic shift and an increase in higher-order
      aberrations when comparing wavefront aberrometry results at postoperative day 1
      with those at postoperative 1 year.

PMID- 25751834
TI  - Repeatability and inter-device agreement for three different methods of
      keratometry: Placido, Scheimpflug, and color LED corneal topography.
AB  - PURPOSE: To determine the repeatability of a color LED corneal topographer
      (Cassini; iOptics, The Hague, The Netherlands) and compare it with Placido and
      Scheimpflug based devices (EyeSys 2000; EyeSys Laboratories, Houston, TX, and
      Pentacam HR; Oculus Optikgerate GmbH, Wetzlar, Germany). METHODS: This
      prospective study involved 20 healthy volunteers (20 eyes) recruited from the
      staff of the Antwerp University Hospital. For each eye, three measurements were
      taken using each device, from which eight parameters describing keratometry and
      astigmatism were derived. Repeatability was assessed using intrasession, within
      subject analysis of variance. Agreement was evaluated between pairs of devices
      with Bland- Altman plots and 95% confidence intervals. RESULTS: The repeatability
      values were good for all three devices, although slightly worse for the Cassini
      than for the other two devices for steep, flat, and mean keratometry. The EyeSys
      showed worse repeatability for the astigmatism axis. EyeSys and Pentacam agreed
      well with each other in terms of mean keratometry, whereas the Cassini gave
      consistently higher values by 0.52 diopters (D) when compared with the EyeSys (P
      < .05, paired t test) and by 0.38 D when compared with the Pentacam (P < .05,
      paired t test). The Cassini provided similar repeatability values (2.31 degrees )
      for the astigmatism axis to the Pentacam (2.22 degrees ), in contrast to the
      EyeSys, which produced much more variable axes (9.0 degrees ) (P < .05, paired t
      test). CONCLUSIONS: Overall, the three devices display comparable repeatability.
      The one exception is the astigmatism axis measurement of the EyeSys. The Cassini
      provides higher keratometry values than the other two devices, but the
      astigmatism axis agrees well with that provided by the Pentacam.

PMID- 25751835
TI  - Corneal topographic astigmatism (CorT) to quantify total corneal astigmatism.
AB  - PURPOSE: To evaluate the performance of corneal topographic astigmatism (CorT)
      based on total corneal power measurements. METHODS: Anterior, posterior, and
      total corneal power measurements of 526 virgin eyes obtained using the CSO Sirius
      tomographer (Costuzione Strumenti Oftalmici, Scandicci, Florence, Italy) were
      analyzed. Individual CorTs were created from each set of data. These CorTs were
      assessed using ocular residual astigmatism (ORA), which quantifies corneo
      refractive differences. A low standard deviation of the ocular residual
      astigmatism (ORAsd) indicates a low variability between corneal astigmatism and
      refractive cylinder. A low mean of the ORA magnitude indicates a close
      correlation of refractive cylinder and corneal astigmatism. RESULTS: The CorT
      based on total corneal power measurements had an ORAsd of 0.30 diopters (D) and a
      mean ORA magnitude of 0.53 D. The CorT candidates based on anterior corneal power
      measurements all had an ORAsd of at least 0.32 D, and the mean ORA magnitudes
      were all 0.64 D or greater. Both the ORAsd and mean ORA magnitude of the CorT
      based on total corneal power measurements were significantly less than those of
      the CorT based on anterior corneal power measurements (both P < .001, as
      estimated via bootstrapping). CONCLUSIONS: The CorT based on total corneal power
      measurements corresponds better, both in variability and closeness, with manifest
      refractive cylinder than the CorT based on anterior corneal power measurements.
      This total CorT would be fundamental when planning toric intraocular lenses or
      limbal relaxing incisions or other corneal astigmatic surgery.

PMID- 25751836
TI  - Repeatability of aberrometric measurements with a new instrument for vision
      analysis based on adaptive optics.
AB  - PURPOSE: To evaluate intersession and intrasession repeatability of aberration
      data obtained with a new visual simulator based on adaptive optics, which
      includes a Hartmann-Shack aberrometer (Adaptive Optics Vision Analyzer; Voptica
      S.L., Murcia, Spain). METHODS: Thirty-one healthy right eyes were included in the
      study. To evaluate intrasession repeatability, three consecutive measurements
      without repositioning the patient or realigning the eye were obtained.
      Intersession repeatability was evaluated in three sessions. Aberrometric data
      computed from the second to the fifth order for a 4-mm pupil were used.
      Statistical analysis included the repeated measures analysis of variance (or the
      Wilcoxon signed rank test), the coefficient of repeatability, the Bland-Altman
      method, and the intraclass correlation coefficient. RESULTS: No significant
      differences in the intrasession and intersession repeatability analysis for any
      of the parameters (P > .05) were found, suggesting a consistent variability of
      the instrument over time. Similar coefficient of repeatability values were
      obtained in the three sessions. The Bland-Altman analysis confirmed differences
      close to zero and the variations were independent of the mean within and between
      sessions. The intersession intraclass correlation coefficient values were
      generally above 0.75, suggesting moderate to high repeatability. However, some
      exceptions were found in the intrasession analysis. CONCLUSIONS: The findings
      suggest that the new instrument provides consistent and repeatable aberrometric
      data. It is therefore a suitable tool to perform consistent and repeatable visual
      simulations.

PMID- 25751838
TI  - Anterior capsule contraction treated by femtosecond laser capsulotomy.
AB  - PURPOSE: To describe a new method to treat severe anterior capsule contraction
      using a femtosecond laser anterior capsulotomy. METHODS: Case report. RESULTS: A
      48-year-old woman with a history of myotonic dystrophy experienced a severe
      contraction of the anterior capsule following an uneventful phacoemulsification
      cataract surgery with a hydrophilic acrylic intraocular lens implanted in the
      capsular bag. A femtosecond laser anterior capsulotomy was performed using a non
      applanating fluid-filled interface. The spectral-domain optical coherence
      tomography imaging system associated with the laser enabled precise centration
      and location of the capsulotomy with a posterior cut located between the anterior
      surface of the intraocular lens and the anterior capsule inner surface. The free
      floating capsulotomy was easily removed after the laser procedure, and 8 days
      postoperatively visual acuity recovered and myopic shift regressed with an
      intraocular lens centered in the capsular bag. CONCLUSIONS: Femtosecond laser
      assisted by a high-resolution imaging system appears to be a safe and efficient
      treatment for severe anterior capsule contraction.

PMID- 25751837
TI  - Evaluation of a New Controlled Point Source LED Glare Tester for Disability Glare
      Detection in Participants With and Without Cataracts.
AB  - PURPOSE: To determine glare-induced change during visual acuity testing in
      patients with and without cataract using the controlled point source light
      emitting diode (LED) glare tester (EpiGlare Tester; Epico, LLC, Columbus, OH), a
      new medical device for identification of glare disability. METHODS: This
      prospective, multicenter study enrolled 40 patients (80 eyes with cataracts) and
      49 control subjects (98 eyes without cataracts). Corrected distance visual acuity
      (CDVA) was measured with and without glare using the EpiGlare Tester as a glare
      source. Functional visual ability was evaluated using driving and glare subscales
      from the Refractive Status Vision Profile questionnaire. The primary efficacy
      measure was change in CDVA measurement with and without glare in patients with
      senile cataract compared to participants without cataract. Secondary efficacy
      measures included correlation of the CDVA change caused by functional glare
      disability and subjective patient and investigator assessments. RESULTS: CDVA
      reduction was greater for patients with cataract, with a mean reduction of -0.49
      +/- 0.3 logMAR, than for participants without cataracts at -0.13 +/- 0.2 logMAR
      (P < .001). This equates to a 5-line Snellen reduction (0.49 logMAR) in patients
      with cataracts and a 1-line reduction (-0.13 logMAR) in patients without
      cataracts. Among patients with cataracts, 83% stated the device accurately
      represented the difficulty experienced while driving at night (P < .001); among
      participants without cataracts, 71% reported being minimally affected by glare
      from the device (P = .003). CONCLUSIONS: A new controlled point source LED glare
      tester demonstrated the adverse effect on visual acuity due to glare in patients
      with cataract, accurately simulated night driving glare issues for patients with
      cataracts, and was rated as easy to use and useful by investigators.

PMID- 25751840
TI  - Ciliary sulcus microcysts as the source of a white-to-white sizing mismatch with
      the implantable Collamer lens.

PMID- 25751839
TI  - Femtosecond laser-assisted cataract surgery after implantation of a transparent
      near vision corneal inlay.
AB  - PURPOSE: To describe two cases of successful femtosecond laser-assisted cataract
      surgery in patients with a transparent hydrogel corneal inlay (Raindrop Near
      Vision Inlay; ReVision Optics, Inc., Lake Forest, CA). METHODS: Case report.
      RESULTS: In both cases, femtosecond laser-assisted cataract surgery was performed
      with the inlay in place. The femtosecond laser pulses were delivered without
      difficulties, and the Raindrop inlay did not interfere with the visualization of
      intraocular structures during surgery. Following implantation of a monofocal
      intraocular lens targeted for plano, both patients experienced improvements in
      their uncorrected distance visual acuity and regained near vision. CONCLUSIONS:
      These two cases suggest that the presence of the Raindrop inlay left in situ does
      not preclude successful femtosecond laser-assisted cataract surgery.

PMID- 25751841
TI  - Persistent stromal scar after PRK and CXL: different preoperative findings,
      similar complication.

PMID- 25751842
TI  - Comparison of corneal shape changes and aberrations induced By FS-LASIK and SMILE
      for myopia.
AB  - PURPOSE: To compare corneal curvatures, corneal power calculations, and higher
      order aberrations (HOAs) of femtosecond laser-assisted LASIK (FS-LASIK) with
      small incision lenticule extraction (SMILE) following surgery for moderate to
      high myopia. METHODS: A retrospective study of 736 eyes of 368 patients treated
      with SMILE and 148 eyes of 74 patients treated with FS-LASIK. Preoperative mean
      spherical equivalent was -7.3 +/- 1.5 diopters in the SMILE group and -7.6 +/-
      1.3 diopters in the FS-LASIK group. Corneal curvatures, corneal power
      calculations performed by ray tracing, and HOAs measured with Scheimpflug
      technology before and 3 months after surgery were analyzed. RESULTS: Corneal
      curvatures changed significantly in the anterior corneal surface, but not in the
      posterior corneal surface, in both groups; after SMILE, the sagittal curvature
      was constant for the central 4-mm diameter, in contrast to FS-LASIK where the
      curvature showed a gradual steepening with increasing diameter. Corneal power
      calculations were different across the cornea depending on the measurement
      diameter between the two groups postoperatively. Measured over a 5-mm zone on the
      total cornea, FS-LASIK induced 0.11 um more coma (P < .001) and 0.13 um higher
      spherical aberration (P < .001) as compared to SMILE; similar results in other
      HOAs were seen for the anterior corneal surface. Negligible differences in HOAs
      were induced on the posterior corneal surface. CONCLUSIONS: SMILE and FS-LASIK
      produced distinct changes in anterior corneal shape evident in different
      postoperative corneal curvatures and power measurements between the two groups.
      Postoperative HOAs were much lower after SMILE as compared to FS-LASIK.

PMID- 25751843
TI  - Application of a hydrogel ocular sealant to avoid recurrence of epithelial
      ingrowth after LASIK enhancement.
AB  - PURPOSE: To report a case of clinically significant epithelial ingrowth after
      LASIK that was successfully treated with a hydrogel ocular sealant in combination
      with flap lifting and scraping technique. METHODS: Case report. RESULTS: A 56
      year-old woman underwent LASIK and a LASIK enhancement procedure in 2002 and
      2012, respectively. Six months after the enhancement, visually significant
      epithelial ingrowth developed in both of her eyes. The left eye was treated with
      flap lifting, scraping, and suturing, and the right eye was treated with a
      hydrogel ocular sealant in combination with flap lifting and scraping. No
      recurrence was evident during a 6-month follow-up period and visual acuity
      improved in both eyes. No adverse effects were noticed. CONCLUSIONS: Recurrent
      epithelial ingrowth may be successfully avoided with the intraoperative use of a
      hydrogel ocular sealant combined with flap lifting and scraping. This approach
      could be used as an alternative to LASIK flap suturing.

PMID- 25751846
TI  - Editor's opinion: don't let winds of change blow patient-provider relationships.

PMID- 25751844
TI  - Energy-efficient ECG compression on wireless biosensors via minimal coherence
      sensing and weighted l1 minimization reconstruction.
AB  - Low energy consumption is crucial for body area networks (BANs). In BAN-enabled
      ECG monitoring, the continuous monitoring entails the need of the sensor nodes to
      transmit a huge data to the sink node, which leads to excessive energy
      consumption. To reduce airtime over energy-hungry wireless links, this paper
      presents an energy-efficient compressed sensing (CS)-based approach for on-node
      ECG compression. At first, an algorithm called minimal mutual coherence pursuit
      is proposed to construct sparse binary measurement matrices, which can be used to
      encode the ECG signals with superior performance and extremely low complexity.
      Second, in order to minimize the data rate required for faithful reconstruction,
      a weighted l1 minimization model is derived by exploring the multisource prior
      knowledge in wavelet domain. Experimental results on MIT-BIH arrhythmia database
      reveals that the proposed approach can obtain higher compression ratio than the
      state-of-the-art CS-based methods. Together with its low encoding complexity, our
      approach can achieve significant energy saving in both encoding process and
      wireless transmission.

PMID- 25751845
TI  - Two-phase greedy pursuit algorithm for automatic detection and characterization
      of transient calcium signaling.
AB  - Ca(2+) plays an important role in the regulation of cellular functions. Local
      calcium events, e.g., calcium sparks, not only bring insights into Ca(2+)
      signaling but also contribute to the understanding of various cellular processes.
      However, it is challenging to detect calcium sparks, due to their transient
      properties and high level of nonstationary noises in microscopic images. Most of
      existing algorithms tend to have limitations for the detection of calcium sparks,
      e.g., empirically defined hard thresholds or poor applicability to nonstationary
      conditions. This paper presents a novel two-phase greedy pursuit (TPGP) algorithm
      for automatic detection and characterization of calcium sparks. In Phase I, a
      coarse-grained search is conducted across the whole image to identify the
      predominant sparks. In Phase II, adaptive basis function model is developed for
      the fine-grained representation of detected sparks. It may be noted that the
      proposed TPGP algorithms overcome the drawback of hard thresholding in most of
      previous approaches. Furthermore, the morphology of detected sparks is
      effectively modeled with multiscale basis functions in Phase II, thereby
      facilitating the analysis of physiological features. We evaluated and validated
      the TPGP algorithms using both real-word and synthetic images with multiple noise
      levels and varying baselines. Experimental results show that TPGP algorithms
      yield better performances than previous hard-thresholding approaches in terms of
      both sensitivities and positive predicted values. The present research provides
      the community a robust tool for the automatic detection and characterization of
      transient calcium signaling.

PMID- 25751847
TI  - A comparative, descriptive study of systemic factors and survival in elderly
      patients with sacral pressure ulcers.
AB  - Sacral pressure ulcers (PUs) are a serious complication in frail elderly
      patients. Thin tissue in the sacral area, low body mass index, and anatomical
      location contribute to the development of sacral PUs. A comparative, descriptive
      study was conducted to identify patient systemic factors associated with sacral
      PUs and to compare survival time in patients with and without PU. All consecutive
      patients with PUs (n = 77) and without sacral PUs (n = 53) admitted to the
      skilled nursing department of a geriatric hospital in Jerusalem, Israel between
      July 1, 2008 and December 31, 2011 were eligible to participate. Charts of
      previously admitted patients were abstracted and patients were prospectively
      followed until discharge, death, or the end of the study. Patient demographics,
      comorbidities, nutritional status, physical and cognitive function (measured
      using the Reisberg's Functional Assessment Staging Tool [FAST], Stages of
      Dementia of Alzheimer Scale, and the Glasgow Coma Scale), PU status, number of
      courses of antibiotic treatment during admission, length of hospitalization, and
      mortality were compared between patients admitted with and without a sacral PU
      using descriptive and univariate statistics. Logistic regression models were used
      to estimate the odds ratio (OR) and 95% confidence intervals (CI) for sacral PU
      versus without PU by study covariate. The association between sacral PU and
      survival time was assessed using Kaplan-Meier models. Patients with a sacral PU
      were significantly older (average age 81.60 +/-10.78 versus 77.06+/-11.19 years
      old, P = 0.02) and had a higher prevalence of dementia (70% versus 30%, P =
      0.007), Parkinson's disease (92.3% versus 7.7%, P = 0.03), and anemia (67.7%
      versus 32.3%, P = 0.06) than patients admitted without a PU. Patients with a
      sacral PU also had a lower body mass index (23.1 versus 25.4, P = 0.04), and
      lower hemoglobin (10.54 versus 11.11, P = 0.03), albumin (26.2 versus 29.7, P =
      0.002), and total protein levels (61.3 versus 65.7, P = 0.04). In addition,
      antibiotic treatment was significantly higher in the patients with PU (50.6%
      versus 28.3%, P = 0.01). Patients with a sacral PU also had significantly lower
      physical and cognitive functioning scores and their median survival time was 70
      days compared to 401 days in the non-PU group (P <0.001). These findings are
      generally consistent with the literature regarding risk factors for PU
      development and confirm the need for preventive measures. In addition, clinicians
      need to address the overall goal of patient care and patient quality of life when
      considering PU management interventions in this patient population. 

PMID- 25751849
TI  - Effects of 35 kHz, low-frequency ultrasound application in vitro on human
      fibroblast morphology and migration patterns.
AB  - Low-frequency ultrasound (LFU) in the frequency range 30-40 kHz administered
      using different delivery methods (waterbath and noncontact spray) has shown
      positive effects on chronic wound healing rates in humans, but the underlying
      mechanisms are only beginning to be explored. To examine the effects of LFU
      delivered at 35 kHz on the morphology and migration of human fibroblasts, real
      time videography was used to record the rate and character of cultured human
      fibroblast migration at 8-hour increments for 48 hours in a wound assay model.
      Cells were treated with 35 kHz LFU or saline only (control). Cellular morphology
      (cell shape, packing, and apparent length) and migration patterns including
      orientation were analyzed using time-lapse videography. LFU delivered at a
      frequency of 35 kHz produced a different pattern of fibroblast migration in vitro
      (varied orientation versus vertical orientation for untreated cells) and altered
      cell morphology compared to controls. The observed pattern of migration was more
      varied and widely distributed across multiple angles versus the predominant
      parallel orientation of the migrating untreated cells. The potential implications
      of these findings on collagen placement in the extracellular matrix, which may
      affect degree of soft tissue scarring, should be further investigated. 

PMID- 25751848
TI  - Effects of systemic erythropoietin on ischemic wound healing in rats.
AB  - Results of in vivo studies have shown erythropoietin (EPO) is associated with
      anti-inflammatory, anti-apoptotic, and cell protective effects on wound healing.
      These effects are dose-dependent. The aim of this study was to evaluate whether
      the duration of EPO treatment affects the healing process in the ischemic wound.
      Forty-two (42) Sprague-Dawley rats were anesthetized, wounded with H-shaped
      flaps, and randomized to 2 groups; Group 1 received 400 u/kg/day EPO and Group 2
      received a saline solution, both via intraperitoneal injection following the
      wounding. All substances were administered once daily at the same time for up to
      10 days after surgery. At days 3, 5, and 10, 7 rats from each group were
      sacrificed. Skin samples were stained with hematoxylin/eosin, viewed under an
      optical microscope at 10X and 40X magnification, and analyzed by blinded
      investigators for re-epithelialization, neovascularization amount and maturation
      of granulation tissue, inflammatory cells, and ulcer healing using an evaluation
      scale where 0 = none; 1 = partial; 2 = complete, but immature/thin: and 4 =
      complete and mature. Blood hemoglobin and hematocrit levels also were measured.
      Data were analyzed using ANOVA one-way test (P <0.05). Hemoglobin and hematocrit
      levels rose while subsequent doses of EPO were administered over time,
      accompanied by a transient surge in healing on day 5, when differences in healing
      scores were significant. Flap necrosis, ulceration, and abscess were noted on
      post-wounding day 10 near the pedicle. The study showed EPO therapy can improve
      wound healing early in the post-wounding period but can reduce wound healing
      after post-injury treatment day 5. Further research is necessary, particularly to
      establish how EPO influences the microcirculation and rheology. 

PMID- 25751850
TI  - Prevalence of Moderate to Severe Obesity Among U.S. Nursing Home Residents, 2000
      2010.
AB  - Obesity rates are high among all age groups, including older adults. Obesity
      negatively affects health and functional ability, increasing the risk for nursing
      home (NH) admission. The current study examines trends over 11 years in moderate
      to severe obesity rates among NH residents. A generalized least squares
      regression model for panel data was used to test the effect of time (years) on
      the rates. A significant increase in rates and significant variation in rates
      were observed. Little research has focused on the issue of obesity in NHs. High
      and increasing rates and variation in rates raise questions on demand and access
      to NH care for obese older adults. Additional research is needed to consider
      factors other than time that may affect NHs' ability to admit moderate to
      severely obese individuals. Understanding these trends will help NHs prepare for
      future demand, ensure equal access, quality care, and financing of services.

PMID- 25751852
TI  - Pathological findings in wild harvested dugongs Dugong dugon of central Torres
      Strait, Australia.
AB  - The dugong Dugong dugon is classified as Vulnerable to extinction but may be
      endangered in some regions. Cause of death in stranded dugongs has not been
      determined in a large proportion of animals examined, with investigations
      hindered by limited information on dugong health and diseases, and paucity of
      knowledge of common or endemic pathological findings. Here we describe
      pathological findings in harvested dugongs from the relatively pristine area of
      central Torres Strait, and we characterise lesions attributable to drowning.
      Other recorded lesions were mild and predominated by host reaction to the
      presence of trematodes within the gastrointestinal tracts, liver and pancreas.
      Ascarid worm burdens were low in comparison to dugongs from developed coastlines.
      Hepatocellular lipofuscin and ferritin pigmentation were commonly observed, more
      pronounced in livers of older animals and concurrent with periportal and bridging
      fibrosis. Lesions attributable to drowning included incomplete collapse of lungs,
      dorsal or diffuse pulmonary congestion, mild intra-alveolar haemorrhage and
      oedema, mild interstitial oedema and rupture of peripheral alveolar septae with
      acute myofibre fragmentation and degeneration. No accumulation of foam or
      aspiration of water or particulate matter was observed, suggesting that dugongs
      'dry drown'. Morphometric features of normal spleen are also presented.
      Characterisation of common pathological findings and those attributable to
      drowning in this species will aid in the interpretation of post mortem findings
      for the significant number of dugongs found deceased along urbanised coastlines. 

PMID- 25751851
TI  - Is the use of intranasal glucocorticosteroids (inGCSs) in children safe?
AB  - It's been 40 years since Niels Mygind publication in British Medical Journal on
      intranasal application of beclomethasonedipropionate aerosol in Allergic
      Rhinitis. Since then the new era in treatment of allergic and non-allergic upper
      airway diseases has begun. This publication presents current concepts on
      application of intranasal glucocorticosteroids in treatment of upper airway
      diseases and in particular of allergic rhinitis and rhinosinusitis. The non
      questionable advantage of intranasal glucocorticosteroids is their strong anti
      inflammatory local action with little impact on general health responsible for
      few and benign side effects. Main way of action of glucocorticosteroids is
      connected with binding to the intracellular glucocorticosteroid receptor and its
      impact on nuclear cytoplasmic transcriptional factors. Glucocorticosteroids
      suppress gene expression of factors responsible for generating and supporting
      inflammatory processes, pro-inflammatory cytokines and chemokines production,
      adhesive molecules expression. It appears that glucocorticosteroids has also
      other mechanisms of action, non-involving intracellular receptors, leading to
      inhibiting of early and late phase of allergic reaction. At the moment there are
      following glucocorticosteroids registered in Poland: beclomethasone, budesonide,
      fluticasone propionate, fluticasone fuorate, mometasonefuorate. Special attention
      earns fuorates as their lateral fuorate ester chain makes this molecules highly
      lipophilic, easily absorbed by nasal mucous membranes epithelium and cell
      membranes phospholipids. This minimizes their general action and maximizes local
      action. According to current state of knowledge topical glucocorticosteroids are
      used in the following upper airway diseases with different inflammatory
      mechanism: allergic rhinitis, non-allergic rhinitis, particularly NARES, acute
      rhinosinusitis, chronic rhinosinusitis with and without nasal polyps, adenoid
      hypertrophy and rhinitis in bronchial asthma.

PMID- 25751853
TI  - Morphological and genetic identification of Anisakis paggiae (Nematoda:
      Anisakidae) in dwarf sperm whale Kogia sima from Brazilian waters.
AB  - Anisakid nematodes have been identified in a wide variety of fish and marine
      mammal species. In Brazil, Anisakis physeteris, A. insignis, A. typica, A.
      nascetti, and those of the A. simplex complex have been reported infecting fishes
      and cetaceans. In this study, specimens collected from a dwarf sperm whale Kogia
      sima (Owen, 1866) stranded on the northeastern coast of Brazil were identified
      through morphological and genetic analyses as A. paggiae. Anisakids were examined
      through differential interference contrast light and scanning electron microscopy
      (SEM). Morphological and morphometric analysis revealed that these specimens
      belonged to Anisakis sp. clade II and more specifically to A. paggiae, exhibiting
      a violin-shaped ventriculus and 3 denticulate caudal plates, which are taxonomic
      characters considered unique to this species. Genetic analysis based on the mtDNA
      cox2 gene confirmed our identification of A. paggiae. Phylogenetic trees using
      both maximum likelihood and neighbor-joining methods revealed a strongly
      supported monophyletic clade (bootstrap support = 100%) with all available A.
      paggiae sequences. Integrative taxonomic analysis allowed the identification of
      A. paggiae for the first time in Brazilian waters, providing new data about their
      geographical distribution. Moreover, here we present the first SEM images of this
      species. 

PMID- 25751854
TI  - Polyphasic characterization reveals the presence of novel fish-associated
      Chryseobacterium spp. in the Great Lakes of North America.
AB  - Recent reports suggest an emergence of novel Chryseobacterium spp. associated
      with aquaculture-reared fish worldwide. Herein, we report on multiple
      Chryseobacterium spp. infecting Great Lakes fishes that are highly similar to
      previously detected isolates from Europe, Africa, and Asia but have never before
      been reported in North America. Polyphasic characterization, which included
      extensive physiological, morphological, and biochemical analyses, fatty acid
      profiling, and phylogenetic analyses based upon partial 16S rRNA gene sequences,
      highlighted the diversity of Great Lakes' fish-associated chryseobacteria and
      also suggested that at least 2 taxa represent potentially novel Chryseobacterium
      spp. Screening for the ability of representative chryseobacteria to elicit
      lesions in experimentally challenged fish showed that they induced varying
      degrees of pathology, some of which were severe and resulted in host death.
      Median lethal dose (LD50) experiments for the isolate that elicited the most
      extensive pathology (Chryseobacterium sp. T28) demonstrated that the LD50
      exceeded 4.5 * 108 cfu, thereby suggesting its role as a facultative fish
      pathogenic bacterium. Histopathological changes in T28-infected fish included
      epithelial hyperplasia of the secondary lamellae and interlamellar space that
      resulted in secondary lamellar fusion, monocytic infiltrate, and mucus cell
      hyperplasia, all of which are consistent with branchitis, along with monocytic
      myositis, hemorrhage within the muscle, liver, adipose tissue, and ovaries,
      spongiosis of white matter of the brain, multifocal edema within the granular
      cell layer of the cerebellar cortex, and renal tubular degeneration and necrosis.
      The findings of this study underscore the widespread presence of chryseobacteria
      infecting Great Lakes fish. 

PMID- 25751855
TI  - Expression of immune-related genes of common carp during cyprinid herpesvirus 3
      infection.
AB  - Fish herpesviruses and their hosts may have coevolved for 400 to 450 million yr.
      During this coexistence, the hosts have equipped themselves with an elaborate
      immune system to defend themselves from invading viruses, whereas the viruses
      have developed strategies to evade host immunity, including the expression of
      cytokine genes that have been captured from the host. Taking advantage of our
      experimental model for cyprinid herpesvirus 3 (CyHV-3) persistence in carp, we
      studied the gene expression of host and virus immune-related genes in each stage
      of infection: acute, persistent and reactivation phases. IFNgamma-1, IFNgamma-2,
      IL-12 and IL-10 host genes, and the CyHV-3 vIL-10 gene (khvIL-10) were highly
      significantly up-regulated in different phases of CyHV-3 infection. Similarly,
      host IL-1beta was up-regulated in the acute phase of CyHV-3 infection. There was
      no significant difference in the expression of host TNFalpha-1 and MHC-II genes
      during all phases of CyHV-3 infection. Based on the expression profile of carp
      immune-related genes in each stage of CyHV-3 infection, we propose a possible
      interaction between carp IL-12, carp IL-10 and khvIL-10 during the course of
      viral infection. To our knowledge, this is the first report on the expression of
      cytokine genes during all phases (acute, persistent and reactivation) of CyHV-3
      infection. 

PMID- 25751858
TI  - Neurotropic mesomycetozoean-like infection in larvae of the southern toad
      Anaxyrus terrestris in Florida, USA.
AB  - As part of a state-wide multispecies survey of amphibian diseases, sampling was
      conducted at Archbold Biological Station, Venus, Florida, USA, on 15 April 2011.
      Gross examination of southern toad (Anaxyrus terrestris) larvae was unremarkable,
      but infections by a mesomycetozoean-like organism were observed in longitudinally
      sectioned routine haematoxylin and eosin-stained histologic slides. In 100% of
      the sectioned specimens examined (n = 5), a high density of the organism,
      representing several developmental stages, was found in the central nervous
      system, mainly in the spinal cord, brain, retina and optic nerve. No host
      inflammatory responses were found to be associated with the parasitic infection.
      Free, mature schizonts were occasionally found in the gill chamber and, more
      commonly, in the dorsal roof area. No organisms were found in other organs
      examined histologically, i.e. liver, kidney, heart, alimentary tract, exocrine
      pancreas and skeletal muscles. Presumptive mesomycetozoean ichthyophonids in
      anurans are usually reported to be pathogenic, especially affecting skeletal
      muscle tissue and causing death. To our knowledge, this is the first report of a
      similar organism infecting primarily the central nervous system in an amphibian. 

PMID- 25751857
TI  - Amphibian pathogens at northern latitudes: presence of chytrid fungus and
      ranavirus in northeastern Canada.
AB  - Infections by the fungal pathogen Batrachochytrium dendrobatidis (Bd) and members
      of the genus Ranavirus (Rv) are increasingly reported as significant determinants
      of amphibian population die-offs. The complexity associated with their
      transmission and spatial distribution leads to an increase in demand for
      comprehensive reporting systems and global mapping of their distribution. Here,
      we document the distribution of these 2 pathogens in a remote northern temperate
      lowland where environmental sensitivity is high, providing important insight into
      the pathogens' natural history and infection patterns. Wood frog Lithobates
      sylvaticus tissues were collected from the James Bay area in northeastern Canada
      and were screened for the presence of Bd and Rv using conventional and real-time
      PCR. Both pathogens were present in the study area, which is the northernmost
      record in eastern North America. Interestingly, different patterns of
      distribution were observed between the eastern and western coasts of James Bay,
      suggesting differences in the spatial and transmission dynamics for each
      pathogen. Anthropogenic introduction may still influence the distribution
      patterns observed, even at these latitudes. The presence of infections in this
      remote area also raises further questions on the risk these pathogens pose to
      northern amphibian communities. We encourage further research in remote locations
      for a better understanding of these pathogens, their transmission dynamics, and
      especially their respective impacts on amphibian populations worldwide. 

PMID- 25751856
TI  - Experimental infections of Pacific oyster Crassostrea gigas using the Australian
      ostreid herpesvirus-1 (OsHV-1) uVar strain.
AB  - In Australia, the spread of the ostreid herpesvirus-1 microvariant (OsHV-1 uVar)
      threatens the Pacific oyster industry. There is an urgent need to develop an
      experimental infection model in order to study the pathogenesis of the virus
      under controlled laboratory conditions. The present study constitutes the first
      attempt to use archived frozen oysters as a source of inoculum, based on the
      Australian OsHV-1 uVar strain. Experiments were conducted to test (1) virus
      infectivity, (2) the dose-response relationship for OsHV-1, and (3) the best
      conditions in which to store infective viral inoculum. Intramuscular injection of
      a viral inoculum consistently led to an onset of mortality 48 h post-injection
      and a final cumulative mortality exceeding 90%, in association with high viral
      loads (1 * 105 to 3 * 107 copies of virus mg-1) in dead individuals. For the
      first time, an infective inoculum was produced from frozen oysters (tissues
      stored at -80 degrees C for 6 mo). Storage of purified viral inoculum at +4
      degrees C for 3 mo provided similar results to use of fresh inoculum, whereas
      storage at -20 degrees C, -80 degrees C and room temperature was detrimental to
      infectivity. A dose-response relationship for OsHV-1 was identified but further
      research is recommended to determine the most appropriate viral concentration for
      development of infection models that would be used for different purposes.
      Overall, this work highlights the best practices and potential issues that may
      occur in the development of a reproducible and transferable infection model for
      studying the pathogenicity of the Australian OsHV-1 strain in Crassostrea gigas
      under experimental conditions. 

PMID- 25751860
TI  - Effect of the copepod parasite Nicothoe astaci on haemolymph chemistry of the
      European lobster Homarus gammarus.
AB  - The gills of the European lobster Homarus gammarus (L.) are susceptible to
      parasitization by the copepod Nicothoe astaci, the lobster louse. This copepod
      feeds on haemolymph of the host and can damage the gills, potentially affecting
      gaseous exchange capabilities. To investigate the host response to the parasite,
      haemolymph levels of total protein, haemocyanin, glucose and ammonia were
      quantified in adult lobsters carrying varying parasite loads. Parasite loads
      correlated positively with total haemolymph protein and haemocyanin
      concentrations but not with glucose or ammonia concentrations. The data suggest
      that lobsters with gills damaged by the feeding activities of N. astaci respond
      by producing higher levels of haemocyanin, which is both a key defence response
      and may compensate for their decreased respiratory functioning. 

PMID- 25751859
TI  - Blue crabs Callinectes sapidus as potential biological reservoirs for white spot
      syndrome virus (WSSV).
AB  - White spot syndrome virus (WSSV) is a virulent pathogen of cultured shrimp and
      was first detected in farms in South Carolina (USA) in 1997 and subsequently in
      wild shrimp in 1999. We screened groups of 1808 wild Atlantic white shrimp
      Litopenaeus setiferus and 300 blue crabs Callinectes sapidus collected from South
      Carolina, Georgia, and Florida for the presence of WSSV using the Shrimple(r)
      immunoassay-strip test, with all positives and random subsets of negatives tested
      by TaqMan real-time PCR and in infectivity bioassays. Of 87 shrimp and 11 crabs
      that tested positive using the Shrimple(r) test, only a single C. sapidus was
      confirmed to be infected with WSSV by PCR and the infectivity bioassay. The data
      indicate that the prevalence of WSSV in these species is low in these
      southeastern US regions, but that C. sapidus may serve as a biological reservoir.

PMID- 25751862
TI  - Focused Magnetic Resonance Coupling Coils for Electromagnetic Therapy
      Applications.
AB  - This paper presents the design and construction of a pair of figure-of-eight
      coils, coupled by magnetic resonance coupling (MRC), which could generate (150
      V/m per Ampere) electric field at the focal points for electromagnetic therapy
      related applications. The E field generated at the targeted site would be
      significantly enhanced under the same amount of current flowing through the MRC
      figure-of-eight coils compared to normal coils, due to the superposition of E
      field contributed by the coils. Furthermore, the MRC figure-of-eight coil is
      designed and the results are verified in theory, simulation, and experiments. In
      the ex vivo tissue measurement, 35% current and 82% ohmic power improvements were
      observed. Since it can enhance the current and ohmic power, the MRC figure-of
      eight coils are promising solutions for electromagnetic therapy applications. The
      potential applications of the coils include noninvasive radio frequency (RF)
      stimulation, thermoacoustic imaging, electromagnetic field therapies, and RF
      ablation, etc. 

PMID- 25751863
TI  - 3-D Stent Detection in Intravascular OCT Using a Bayesian Network and Graph
      Search.
AB  - Worldwide, many hundreds of thousands of stents are implanted each year to
      revascularize occlusions in coronary arteries. Intravascular optical coherence
      tomography is an important emerging imaging technique, which has the resolution
      and contrast necessary to quantitatively analyze stent deployment and tissue
      coverage following stent implantation. Automation is needed, as current, it takes
      up to 16 h to manually analyze hundreds of images and thousands of stent struts
      from a single pullback. For automated strut detection, we used image formation
      physics and machine learning via a Bayesian network, and 3-D knowledge of stent
      structure via graph search. Graph search was done on en face projections using
      minimum spanning tree algorithms. Depths of all struts in a pullback were
      simultaneously determined using graph cut. To assess the method, we employed the
      largest validation data set used so far, involving more than 8000 clinical images
      from 103 pullbacks from 72 patients. Automated strut detection achieved a 0.91+/
      0.04 recall, and 0.84+/-0.08 precision. Performance was robust in images of
      varying quality. This method can improve the workflow for analysis of stent
      clinical trial data, and can potentially be used in the clinic to facilitate real
      time stent analysis and visualization, aiding stent implantation.

PMID- 25751861
TI  - Domain Transfer Learning for MCI Conversion Prediction.
AB  - Machine learning methods have successfully been used to predict the conversion of
      mild cognitive impairment (MCI) to Alzheimer's disease (AD), by classifying MCI
      converters (MCI-C) from MCI nonconverters (MCI-NC). However, most existing
      methods construct classifiers using data from one particular target domain (e.g.,
      MCI), and ignore data in other related domains (e.g., AD and normal control (NC))
      that may provide valuable information to improve MCI conversion prediction
      performance. To address is limitation, we develop a novel domain transfer
      learning method for MCI conversion prediction, which can use data from both the
      target domain (i.e., MCI) and auxiliary domains (i.e., AD and NC). Specifically,
      the proposed method consists of three key components: 1) a domain transfer
      feature selection component that selects the most informative feature-subset from
      both target domain and auxiliary domains from different imaging modalities; 2) a
      domain transfer sample selection component that selects the most informative
      sample-subset from the same target and auxiliary domains from different data
      modalities; and 3) a domain transfer support vector machine classification
      component that fuses the selected features and samples to separate MCI-C and MCI
      NC patients. We evaluate our method on 202 subjects from the Alzheimer's Disease
      Neuroimaging Initiative (ADNI) that have MRI, FDG-PET, and CSF data. The
      experimental results show the proposed method can classify MCI-C patients from
      MCI-NC patients with an accuracy of 79.4%, with the aid of additional domain
      knowledge learned from AD and NC. 

PMID- 25751864
TI  - Oriented correlation models of distorted natural images with application to
      natural stereopair quality evaluation.
AB  - In recent years, bandpass statistical models of natural, photographic images of
      the world have been used with great success to solve highly diverse problems
      involving image representation, image repair, image quality assessment (IQA), and
      image compression. One missing element has been a reliable and generic model of
      spatial image correlation that reflects the distributions of oriented and
      relatively oriented spatial structures. We have developed such a model for
      bandpass pristine images and have generalized it here to also capture the spatial
      correlation structure of bandpass distorted images. The model applies well to
      both luminance and depth images. As a demonstration of the usefulness of the
      generalized model, we develop a new no-reference stereoscopic/3D IQA framework,
      dubbed stereoscopic/3D blind image naturalness quality index, which utilizes both
      univariate and generalized bivariate natural scene statistics (NSS) models. We
      first validate the robustness and effectiveness of these novel bivariate and
      correlation NSS features extracted from distorted stereopairs, then demonstrate
      that they are predictive of distortion severity. Our experimental results show
      that the resulting 3D image quality predictor based in part on the new model
      outperforms state-of-the-art full- and no-reference 3D IQA algorithms on both
      symmetrically and asymmetrically distorted stereoscopic image pairs.

PMID- 25751865
TI  - Matching of large images through coupled decomposition.
AB  - In this paper, we address the problem of fast and accurate extraction of points
      that correspond to the same location (named tie-points) from pairs of large-sized
      images. First, we conduct a theoretical analysis of the performance of the full
      image matching approach, demonstrating its limitations when applied to large
      images. Subsequently, we introduce a novel technique to impose spatial
      constraints on the matching process without employing subsampled versions of the
      reference and the target image, which we name coupled image decomposition. This
      technique splits images into corresponding subimages through a process that is
      theoretically invariant to geometric transformations, additive noise, and global
      radiometric differences, as well as being robust to local changes. After
      presenting it, we demonstrate how coupled image decomposition can be used both
      for image registration and for automatic estimation of epipolar geometry.
      Finally, coupled image decomposition is tested on a data set consisting of
      several planetary images of different size, varying from less than one megapixel
      to several hundreds of megapixels. The reported experimental results, which
      includes comparison with full-image matching and state-of-the-art techniques,
      demonstrate the substantial computational cost reduction that can be achieved
      when matching large images through coupled decomposition, without at the same
      time compromising the overall matching accuracy. 

PMID- 25751866
TI  - Multiscale logarithm difference edgemaps for face recognition against varying
      lighting conditions.
AB  - Lambertian model is a classical illumination model consisting of a surface albedo
      component and a light intensity component. Some previous researches assume that
      the light intensity component mainly lies in the large-scale features. They adopt
      holistic image decompositions to separate it out, but it is difficult to decide
      the separating point between large-scale and small-scale features. In this paper,
      we propose to take a logarithm transform, which can change the multiplication of
      surface albedo and light intensity into an additive model. Then, a difference
      (substraction) between two pixels in a neighborhood can eliminate most of the
      light intensity component. By dividing a neighborhood into subregions, edgemaps
      of multiple scales can be obtained. Then, each edgemap is multiplied by a weight
      that can be determined by an independent training scheme. Finally, all the
      weighted edgemaps are combined to form a robust holistic feature map. Extensive
      experiments on four benchmark data sets in controlled and uncontrolled lighting
      conditions show that the proposed method has promising results, especially in
      uncontrolled lighting conditions, even mixed with other complicated variations. 

PMID- 25751867
TI  - Fast Determination of the Planar Body Segment Inertial Parameters Using
      Affordable Sensors.
AB  - This study aimed at developing and evaluating a new method for the fast and
      reliable identification of body segment inertial parameters with a planar model
      using affordable sensors. A Kinect sensor, with a new marker-based tracking
      system, and a Wii balance board were used as an affordable and portable motion
      capture system. A set of optimal exciting motions was used in a biofeedback
      interface to identify the body segment parameters. The method was validated with
      12 subjects performing various standardized motions. The same dynamometric
      quantities estimated both with the proposed system and, as a reference, with a
      laboratory grade force-plate were compared. The results showed that the proposed
      method could successfully estimate the resultant moment and the vertical ground
      reaction force (rms errors less than 8 Nm and 12 N, respectively). Finally, when
      local segment values were artificially varied, the proposed method was able to
      detect and estimate the additional masses accurately and with an error of less
      than 0.5 Kg, contrary to values generated with commonly used anthropometric
      tables. 

PMID- 25751868
TI  - A Computational Framework for Electrical Stimulation of Vestibular Nerve.
AB  - The vestibular organs are very important to generate reflexes critical for
      stabilizing gaze and body posture. Vestibular diseases significantly reduce the
      quality of life of people who are affected by them. Some research groups have
      recently started developing vestibular neuroprostheses to mitigate these
      symptoms. However, many scientific and technological issues need to be addressed
      to optimise their use in clinical trials. We developed a computational model able
      to mimic the response of human vestibular nerves and which can be exploited for
      "in-silico" testing of new strategies to design implantable vestibular
      prostheses. First, a digital model of the vestibular system was reconstructed
      from anatomical data. Monopolar stimulation was delivered at different positions
      and distances from ampullary nerves. The electrical potential induced by the
      injected current was computed through finite-element methods and drove extra
      cellular stimulation of fibers in the vestibular, facial, and cochlear nerves.
      The electrical activity of vestibular nerves and the resulting eye movements
      elicited by different stimulation protocols were investigated. A set of electrode
      configurations was analyzed in terms of selectivity at increasing injected
      current. Electrode position along the nerve plays a major role in producing
      undesired activity in other nontargeted nerves, whereas distance from the fiber
      does not significantly affect selectivity. Indications are provided to minimize
      misalignment in nonoptimal electrode locations. Eye movements elicited by the
      different stimulation protocols are calculated and compared to experimental
      values, for the purpose of model validation. 

PMID- 25751869
TI  - Design and construction of the lawnmower, an artificial burnt-bridges motor.
AB  - Molecular motors of the cell are protein-based, nanoscale machines, which use a
      variety of strategies to transduce chemical energy into mechanical work in the
      presence of a large thermal background. The design and construction of artificial
      molecular motors is one approach to better understand their basic physical
      principles. Here, we propose the concept of a protein-based, burnt-bridges
      ratchet, inspired by biological examples. Our concept, the lawnmower, utilizes
      protease blades to cleave peptide substrates, and uses the asymmetric substrate
      product interface arising from productive cleavage to bias subsequent diffusion
      on the track (lawn). Following experimental screening to select a protease to act
      as the motor's blades, we chemically couple trypsin to quantum dots and
      demonstrate activity of the resulting lawnmower construct in solution.
      Accompanying Brownian dynamics simulations illustrate the importance for
      processivity of correct protease density on the quantum dot and spacing of
      substrates on the track. These results lay the groundwork for future tests of the
      protein-based lawnmower's motor performance characteristics. 

PMID- 25751870
TI  - Predicting the Release of Chemotherapeutics From the Core of Polymeric Micelles
      Using Ultrasound.
AB  - In this paper, the estimation of acoustic drug release from micelles is
      addressed. The release is measured as a decrease in fluorescence once ultrasound
      is applied. Initially, a Kalman filter is used to fuse the drug encapsulation
      (calculated as 100 %-release%) dynamics and measurements. Since the measurements'
      noise statistics are not known a priori, the encapsulation estimate is not
      optimal. Therefore, an approach is proposed to adaptively estimate the drug
      release given the statistical properties of the measurements. In this approach, a
      number of measurement covariance magnitudes are hypothesized. A Kalman filter is
      used to obtain the estimate of the acoustic release given each hypothesized
      measurement noise covariance. Simultaneously, the probabilities of these
      measurement covariance hypotheses are sequentially computed as the measurements
      and the predicted release estimates are obtained. Finally, the optimal release
      estimate is obtained by probabilistically adding the estimates from the
      hypothesized Kalman filter estimates. The proposed algorithms are first tested
      using a simulation environment. Subsequently, experimental results are shown to
      validate their performance. The experiments conducted cover various ultrasonic
      power densities for both non-targeted and targeted micelles.

PMID- 25751871
TI  - Microfluidic-assisted fabrication of flexible and location traceable organo
      motor.
AB  - In this paper, we fabricate a flexible and location traceable micromotor, called
      organo-motor, assisted by microfluidic devices and with high throughput. The
      organo-motors are composed of organic hydrogel material, poly (ethylene glycol)
      diacrylate (PEGDA), which can provide the flexibility of their structure. For
      spatial and temporal traceability of the organo-motors under magnetic resonance
      imaging (MRI), superparamagnetic iron oxide nanoparticles (SPION; Fe3O4) were
      incorporated into the PEGDA microhydrogels. Furthermore, a thin layer of platinum
      (Pt) was deposited onto one side of the SPION-PEGDA microhydrogels providing
      geometrical asymmetry and catalytic propulsion in aqueous fluids containing
      hydrogen peroxide solution, H2O2. Furthermore, the motion of the organo-motor was
      controlled by a small external magnet enabled by the presence of SPION in the
      motor architecture.

PMID- 25751872
TI  - Diffusiophoretic self-propulsion for partially catalytic spherical colloids.
AB  - Colloidal spheres with a partial platinum surface coating perform autophoretic
      motion when suspended in hydrogen peroxide solution. We present a theoretical
      analysis of the self-propulsion velocity of these particles using a continuum
      multi-component, self-diffusiophoretic model. With this model as a basis, we show
      how the slip-layer approximation can be derived and in which limits it holds.
      First, we consider the differences between the full multi-component model and the
      slip-layer approximation. Then the slip model is used to demonstrate and explore
      the sensitive nature of the particle's velocity on the details of the molecule
      surface interaction. We find a strong asymmetry in the dependence of the
      colloid's velocity as a function of the level of catalytic coating, when there is
      a different interaction between the solute and solvent molecules and the inert
      and catalytic part of the colloid, respectively. The direction of motion can even
      be reversed by varying the level of the catalytic coating. Finally, we
      investigate the robustness of these results with respect to variations in the
      reaction rate near the edge between the catalytic and inert parts of the
      particle. Our results are of significant interest to the interpretation of
      experimental results on the motion of self-propelled particles. 

PMID- 25751873
TI  - Computational study of interdependence between hemagglutinin and neuraminidase of
      pandemic 2009 H1N1.
AB  - Influenza type A viruses are classified into subtypes based on their two surface
      proteins, hemagglutinin (HA) and neuraminidase (NA). The HA protein facilitates
      the viral binding and entering a host cell and the NA protein helps the release
      of viral progeny from the infected cell. The complementary roles of HA and NA
      entail their collaboration, which has important implications for viral
      replication and fitness. The HA protein from early strains of pandemic 2009 H1N1
      of swine origin preferentially binds to human type receptors with a weak binding
      to avian type receptors. This virus caused several human deaths in December 2013
      in Texas, USA, which motivated us to investigate the changes of genetic features
      that might contribute to the surged virulence of the virus. Our time series
      analysis on the strains of this virus collected from 2009 to 2013 implied that
      the HA binding preference of this virus in USA, Europe, and Asia has been the
      characteristic of swine H1N1 virus since 2009. However, its characteristic of
      seasonal human H1N1 and its binding avidity for avian type receptors both were on
      steady rise and had a clear increase in 2013 with American strains having the
      sharpest surge. The first change could enhance the viral transmission and
      replication in humans and the second could increase its ability to cause
      infection deep in lungs, which might account for the recent human deaths in
      Texas. In light of HA and NA coadaptation and evolutionary interactions, we also
      explored the NA activity of this virus to reveal the functional balance between
      HA and NA during the course of virus evolution. Finally we identified amino acid
      substitutions in HA and NA of the virus that were critical for the observed
      evolution. 

PMID- 25751874
TI  - Influence of Surface State on Biochemical Sensing Using SiGe Nanowire.
AB  - Nanowires are extensively used to fabricate highly sensitive electrical sensors
      for detection of biological and chemical species. The hole mobility can be
      promoted by the increasing Ge fraction in SiGe, achieved by the oxidation-induced
      Ge condensation. However, oxidation increases the number of surface states, which
      brings the nonnegligible contribution in mobility degradation. In this work, 3
      aminopropyltrimethoxysilane (APTMS) was used as a biochemical reagent to modify
      the surface of SiGe nanowires, then bonding to bio-linker, bis (3-sulfo-N
      hydroxysuccinimide ester) sodium salt (BS3). Various methods have been proposed
      for increasing sensitivity of boron-doped SiGe nanowires, such as capping layer,
      surface treatment, and annealing temperature.

PMID- 25751875
TI  - Very sparse LSSVM reductions for large-scale data.
AB  - Least squares support vector machines (LSSVMs) have been widely applied for
      classification and regression with comparable performance with SVMs. The LSSVM
      model lacks sparsity and is unable to handle large-scale data due to
      computational and memory constraints. A primal fixed-size LSSVM (PFS-LSSVM)
      introduce sparsity using Nystrom approximation with a set of prototype vectors
      (PVs). The PFS-LSSVM model solves an overdetermined system of linear equations in
      the primal. However, this solution is not the sparsest. We investigate the
      sparsity-error tradeoff by introducing a second level of sparsity. This is done
      by means of L0 -norm-based reductions by iteratively sparsifying LSSVM and PFS
      LSSVM models. The exact choice of the cardinality for the initial PV set is not
      important then as the final model is highly sparse. The proposed method overcomes
      the problem of memory constraints and high computational costs resulting in
      highly sparse reductions to LSSVM models. The approximations of the two models
      allow to scale the models to large-scale datasets. Experiments on real-world
      classification and regression data sets from the UCI repository illustrate that
      these approaches achieve sparse models without a significant tradeoff in errors. 

PMID- 25751876
TI  - Joint Learning of Multiple Sparse Matrix Gaussian Graphical Models.
AB  - We consider joint learning of multiple sparse matrix Gaussian graphical models
      and propose the joint matrix graphical Lasso to discover the conditional
      independence structures among rows (columns) in the matrix variable under
      distinct conditions. The proposed approach borrows strength across the different
      graphical models and is based on the maximum likelihood with penalized row and
      column precision matrices, respectively. In particular, our model is more
      parsimonious and flexible than the joint vector graphical models. Furthermore, we
      establish the asymptotic properties of our model on consistency and sparsistency.
      And the asymptotic analysis shows that our model enjoys a better convergence rate
      than the joint vector graphical models. Extensive simulation experiments
      demonstrate that our methods outperform state-of-the-art methods in identifying
      graphical structures and estimating precision matrices. Moreover, the
      effectiveness of our methods is also illustrated via a real data set analysis.
      Sparsistency is shorthand for consistency of the sparsity pattern of the
      parameters. 

PMID- 25751877
TI  - Infinite horizon self-learning optimal control of nonaffine discrete-time
      nonlinear systems.
AB  - In this paper, a novel iterative adaptive dynamic programming (ADP)-based
      infinite horizon self-learning optimal control algorithm, called generalized
      policy iteration algorithm, is developed for nonaffine discrete-time (DT)
      nonlinear systems. Generalized policy iteration algorithm is a general idea of
      interacting policy and value iteration algorithms of ADP. The developed
      generalized policy iteration algorithm permits an arbitrary positive semidefinite
      function to initialize the algorithm, where two iteration indices are used for
      policy improvement and policy evaluation, respectively. It is the first time that
      the convergence, admissibility, and optimality properties of the generalized
      policy iteration algorithm for DT nonlinear systems are analyzed. Neural networks
      are used to implement the developed algorithm. Finally, numerical examples are
      presented to illustrate the performance of the developed algorithm. 

PMID- 25751879
TI  - Synchronization in Networks of Linearly Coupled Dynamical Systems via Event
      Triggered Diffusions.
AB  - In this paper, we utilize event-triggered coupling configurations to realize
      synchronization of linearly coupled dynamical systems. Here, the diffusion
      couplings are set up from the latest observations of the nodes and their
      neighborhood and the next observation time is triggered by the proposed criteria
      based on the local neighborhood information as well. Two scenarios are
      considered: 1) continuous monitoring, in which each node can observe its
      neighborhood's instantaneous states and 2) discrete monitoring, in which each
      node can obtain only its neighborhood's states at the same time point when the
      coupling term is triggered. In both the cases, we prove that if the system with
      persistent coupling can synchronize, then these event-triggered coupling
      strategies can synchronize the system too. 

PMID- 25751878
TI  - Error bounds of adaptive dynamic programming algorithms for solving undiscounted
      optimal control problems.
AB  - In this paper, we establish error bounds of adaptive dynamic programming
      algorithms for solving undiscounted infinite-horizon optimal control problems of
      discrete-time deterministic nonlinear systems. We consider approximation errors
      in the update equations of both value function and control policy. We utilize a
      new assumption instead of the contraction assumption in discounted optimal
      control problems. We establish the error bounds for approximate value iteration
      based on a new error condition. Furthermore, we also establish the error bounds
      for approximate policy iteration and approximate optimistic policy iteration
      algorithms. It is shown that the iterative approximate value function can
      converge to a finite neighborhood of the optimal value function under some
      conditions. To implement the developed algorithms, critic and action neural
      networks are used to approximate the value function and control policy,
      respectively. Finally, a simulation example is given to demonstrate the
      effectiveness of the developed algorithms. 

PMID- 25751880
TI  - Simultaneous Computation of Two Independent Tasks Using Reservoir Computing Based
      on a Single Photonic Nonlinear Node With Optical Feedback.
AB  - In this brief, we numerically demonstrate a photonic delay-based reservoir
      computing system, which processes, in parallel, two independent computational
      tasks even when the two tasks have unrelated input streams. Our approach is based
      on a single-longitudinal mode semiconductor ring laser (SRL) with optical
      feedback. The SRL emits in two directional optical modes. Each directional mode
      processes one individual task to mitigate possible crosstalk. We illustrate the
      feasibility of our scheme by analyzing the performance on two benchmark tasks: 1)
      chaotic time series prediction and 2) nonlinear channel equalization. We identify
      some feedback configurations for which the results for simultaneous
      prediction/classification indicate a good performance, but with slight
      degradation (as compared with the performance obtained for single task
      processing) due to nonlinear and linear interactions between the two directional
      modes of the laser. In these configurations, the system performs well on both
      tasks for a broad range of the parameters. 

PMID- 25751881
TI  - Multistability for Delayed Neural Networks via Sequential Contracting.
AB  - In this paper, we explore a variety of new multistability scenarios in the
      general delayed neural network system. Geometric structure embedded in equations
      is exploited and incorporated into the analysis to elucidate the underlying
      dynamics. Criteria derived from different geometric configurations lead to
      disparate numbers of equilibria. A new approach named sequential contracting is
      applied to conclude the global convergence to multiple equilibrium points of the
      system. The formulation accommodates both smooth sigmoidal and piecewise-linear
      activation functions. Several numerical examples illustrate the present analytic
      theory. 

PMID- 25751882
TI  - Layered Ensemble Architecture for Time Series Forecasting.
AB  - Time series forecasting (TSF) has been widely used in many application areas such
      as science, engineering, and finance. The phenomena generating time series are
      usually unknown and information available for forecasting is only limited to the
      past values of the series. It is, therefore, necessary to use an appropriate
      number of past values, termed lag, for forecasting. This paper proposes a layered
      ensemble architecture (LEA) for TSF problems. Our LEA consists of two layers,
      each of which uses an ensemble of multilayer perceptron (MLP) networks. While the
      first ensemble layer tries to find an appropriate lag, the second ensemble layer
      employs the obtained lag for forecasting. Unlike most previous work on TSF, the
      proposed architecture considers both accuracy and diversity of the individual
      networks in constructing an ensemble. LEA trains different networks in the
      ensemble by using different training sets with an aim of maintaining diversity
      among the networks. However, it uses the appropriate lag and combines the best
      trained networks to construct the ensemble. This indicates LEAs emphasis on
      accuracy of the networks. The proposed architecture has been tested extensively
      on time series data of neural network (NN)3 and NN5 competitions. It has also
      been tested on several standard benchmark time series data. In terms of
      forecasting accuracy, our experimental results have revealed clearly that LEA is
      better than other ensemble and nonensemble methods. 

PMID- 25751883
TI  - Graph Embedded Extreme Learning Machine.
AB  - In this paper, we propose a novel extension of the extreme learning machine (ELM)
      algorithm for single-hidden layer feedforward neural network training that is
      able to incorporate subspace learning (SL) criteria on the optimization process
      followed for the calculation of the network's output weights. The proposed graph
      embedded ELM (GEELM) algorithm is able to naturally exploit both intrinsic and
      penalty SL criteria that have been (or will be) designed under the graph
      embedding framework. In addition, we extend the proposed GEELM algorithm in order
      to be able to exploit SL criteria in arbitrary (even infinite) dimensional ELM
      spaces. We evaluate the proposed approach on eight standard classification
      problems and nine publicly available datasets designed for three problems related
      to human behavior analysis, i.e., the recognition of human face, facial
      expression, and activity. Experimental results denote the effectiveness of the
      proposed approach, since it outperforms other ELM-based classification schemes in
      all the cases. 

PMID- 25751884
TI  - On Integral Invariants for Effective 3-D Motion Trajectory Matching and
      Recognition.
AB  - Motion trajectories tracked from the motions of human, robots, and moving objects
      can provide an important clue for motion analysis, classification, and
      recognition. This paper defines some new integral invariants for a 3-D motion
      trajectory. Based on two typical kernel functions, we design two integral
      invariants, the distance and area integral invariants. The area integral
      invariants are estimated based on the blurred segment of noisy discrete curve to
      avoid the computation of high-order derivatives. Such integral invariants for a
      motion trajectory enjoy some desirable properties, such as computational
      locality, uniqueness of representation, and noise insensitivity. Moreover, our
      formulation allows the analysis of motion trajectories at a range of scales by
      varying the scale of kernel function. The features of motion trajectories can
      thus be perceived at multiscale levels in a coarse-to-fine manner. Finally, we
      define a distance function to measure the trajectory similarity to find similar
      trajectories. Through the experiments, we examine the robustness and
      effectiveness of the proposed integral invariants and find that they can capture
      the motion cues in trajectory matching and sign recognition satisfactorily. 

PMID- 25751885
TI  - Fuzzy Adaptive Quantized Control for a Class of Stochastic Nonlinear Uncertain
      Systems.
AB  - In this paper, a fuzzy adaptive approach for stochastic strict-feedback nonlinear
      systems with quantized input signal is developed. Compared with the existing
      research on quantized input problem, the existing works focus on quantized
      stabilization, while this paper considers the quantized tracking problem, which
      recovers stabilization as a special case. In addition, uncertain nonlinearity and
      the unknown stochastic disturbances are simultaneously considered in the
      quantized feedback control systems. By putting forward a new nonlinear
      decomposition of the quantized input, the relationship between the control signal
      and the quantized signal is established, as a result, the major technique
      difficulty arising from the piece-wise quantized input is overcome. Based on
      fuzzy logic systems' universal approximation capability, a novel fuzzy adaptive
      tracking controller is constructed via backstepping technique. The proposed
      controller guarantees that the tracking error converges to a neighborhood of the
      origin in the sense of probability and all the signals in the closed-loop system
      remain bounded in probability. Finally, an example illustrates the effectiveness
      of the proposed control approach. 

PMID- 25751887
TI  - Requirements for manuscript submission: what every author needs to know and
      comply with to facilitate the review process.

PMID- 25751893
TI  - [How to write bibliographies for citing domestic academic resources].

PMID- 25751886
TI  - Emergency transcatheter aortic valve replacement in patients with cardiogenic
      shock due to acutely decompensated aortic stenosis.
AB  - AIMS: To assess outcomes of TAVR as a rescue therapy in patients with cardiogenic
      shock due to acutely decompensated aortic stenosis. METHODS AND RESULTS: Of 771
      high-risk patients who underwent TAVR, 27 (3.5%; 78+/-9 years; 12 men) were
      treated emergently due to acutely decompensated aortic stenosis with cardiogenic
      shock. SAPIEN and CoreValve prostheses were implanted in 11 and 16 patients,
      respectively: the transfemoral access route was used in 25. Three patients died
      within 72 hours of successful valve deployment, and a further six died within a
      month, giving a 30-day mortality of 33.3%, which was significantly higher than in
      electively treated patients (7.7%, p<0.0001). Univariate predictors of 30-day
      mortality in cardiogenic-shock patients were baseline cardiac output <3.0 l/min,
      reduced cardiac power index, impaired renal function, and mechanical ventilation,
      as well as severe acute kidney injury after TAVR. Estimated one-year survival was
      59.3% in emergently and 82.7% in electively treated patients (p=0.0009). However,
      30-day landmark analysis showed no difference in cumulative survival between TAVR
      modalities. In cardiogenic-shock patients without concomitant reduced cardiac
      output and impaired renal function at baseline (n=22), estimated one-year
      survival was 72.7%. CONCLUSIONS: TAVR should be considered a reasonable rescue
      therapy in patients with cardiogenic shock secondary to decompensated aortic
      stenosis.

PMID- 25751890
TI  - [The possibility of tenofovir monotherapy as a rescue therapy in patients with
      chronic hepatitis B].

PMID- 25751897
TI  - [Advanced practice nursing: the initial phase].

PMID- 25751891
TI  - [A case of biliary cystadenocarcinoma mistaken for liver abscess].

PMID- 25751894
TI  - Doctoral and post-doctoral research - a priority of the  Romanian postgraduate
      education system (Doc-Postdoc).

PMID- 25751895
TI  - [Empowerment through recruitment: an illusion?].

PMID- 25751896
TI  - [The Marine Cross Days: mental health, toward a change in paradigm?].

PMID- 25751892
TI  - [Are repeated fecal immunochemical tests effective for detecting advanced
      colorectal neoplasia in first-degree relatives of patients with colorectal
      cancers?].

PMID- 25751898
TI  - [A look at long-term hospitalization in psychiatry].

PMID- 25751889
TI  - Structure of bone morphogenetic protein 9 procomplex.
AB  - Bone morphogenetic proteins (BMPs) belong to the TGF-beta family, whose 33
      members regulate multiple aspects of morphogenesis. TGF-beta family members are
      secreted as procomplexes containing a small growth factor dimer associated with
      two larger prodomains. As isolated procomplexes, some members are latent, whereas
      most are active; what determines these differences is unknown. Here, studies on
      pro-BMP structures and binding to receptors lead to insights into mechanisms that
      regulate latency in the TGF-beta family and into the functions of their highly
      divergent prodomains. The observed open-armed, nonlatent conformation of pro-BMP9
      and pro-BMP7 contrasts with the cross-armed, latent conformation of pro-TGF
      beta1. Despite markedly different arm orientations in pro-BMP and pro-TGF-beta,
      the arm domain of the prodomain can similarly associate with the growth factor,
      whereas prodomain elements N- and C-terminal to the arm associate differently
      with the growth factor and may compete with one another to regulate latency and
      stepwise displacement by type I and II receptors. Sequence conservation suggests
      that pro-BMP9 can adopt both cross-armed and open-armed conformations. We propose
      that interactors in the matrix stabilize a cross-armed pro-BMP conformation and
      regulate transition between cross-armed, latent and open-armed, nonlatent pro-BMP
      conformations. 

PMID- 25751899
TI  - [Management of mental disorders: 4 challenges to compensate for the French
      delay].

PMID- 25751900
TI  - [A supplement to the nursing diploma].

PMID- 25751903
TI  - [Launching the SocleCare initiative in Belgium].

PMID- 25751902
TI  - [Schizophrenia: drug free approaches to weight loss].

PMID- 25751904
TI  - [A new antidepressant: vortioxetine].

PMID- 25751901
TI  - [Adolescent self mutilation, mental risk factor in adulthood].

PMID- 25751907
TI  - [Mental disorders and dangerous acting out].
AB  - The major mental disorders which are most likely to lead to dangerous acting out
      are adult psychoses (schizophrenia and paranoia) and severe mood disorders (major
      depressive episodes and mania). Good knowledge of the symptomatology of these
      pathologies and their identification can help to anticipate and prevent much of
      the violence which people with these disorders may inflict on others or
      themselves. After mental assessment, those who commit wrongful and criminal acts
      may be ruled to be criminally irresponsible. They are then handed over to the
      relevant health care authorities for treatment for their mental disorders.

PMID- 25751909
TI  - [Preventing dangerous psychotic acting out].
AB  - Delusions of having been wronged, of persecution, of having a mission or order to
      execute, are frequently the causes of dangerous psychotic acting out. The regular
      clinical assessment of these patients and their treatment is essential for
      preventing this acting out, which can have dramatic consequences on the potential
      victims. If there is a treatment indication but refusal on the part of the
      patient to cooperate, it is necessary to resort to treatment without the
      patient's consent.

PMID- 25751906
TI  - [Transitions in all its forms].

PMID- 25751911
TI  - [Acting out: a risk for the caregiver too].
AB  - Some clinical situations can disrupt the containment approach of caregivers. In
      such cases, psychiatric nurses must be careful care not to deviate from their
      approach or else run the risk of giving ill-adapted responses, synonymous with
      acting out. The institute and its organisation can offer opportunities for
      clinical reflection to ensure that the expression and experience of the
      caregivers is taken into consideration, thereby reducing the negative
      countertransferences.

PMID- 25751905
TI  - [Inflammatory status during pregnancy and schizophrenia].

PMID- 25751908
TI  - [Contemplating one's own death to prevent suicidal acts].
AB  - In the framework of a helping relationship with a person in suicidal crisis,
      contemplating one's own death can help to prevent suicidal act. Due to the
      psychological experiences at work, it is important for the caregiver to have
      thought about and accepted their own existential finiteness, a process which
      enables them to provide better support for the person in severe distress.

PMID- 25751910
TI  - [Relaxation to defuse acting out for dangerous schizophrenics].
AB  - Relaxation is often considered as a contraindication in the management of
      schizophrenics. An experiment carried out with dangerous schizophrenics at the
      unit for dangerous patients at Cadillac general hospital revealed that, on the
      contrary, such an opinion is not necessarily valid in all cases. Indeed, for many
      of these patients, relaxation can have positive effects on their clinical state.
      As with its other indications, relaxation must be practised by clinicians who
      have an in-depth knowledge of techniques to use and of mental disorders treated
      in that way.

PMID- 25751912
TI  - [Outpatient cannabis withdrawal programme].
AB  - Cannabis is the most consumed illicit substance in France, and its use can lead
      to dependency. Lille university hospital, le Pari association, offers patients
      wanting to stop using cannabis a support therapy based on positive feedback led
      by nurses, as well as symptomatic treatment of anxiety and sleep disorders.

PMID- 25751888
TI  - Myosin VI deafness mutation prevents the initiation of processive runs on actin.
AB  - Mutations in the reverse-direction myosin, myosin VI, are associated with
      deafness in humans and mice. A myosin VI deafness mutation, D179Y, which is in
      the transducer of the motor, uncoupled the release of the ATP hydrolysis product,
      inorganic phosphate (Pi), from dependency on actin binding and destroyed the
      ability of single dimeric molecules to move processively on actin filaments. We
      observed that processive movement is rescued if ATP is added to the mutant dimer
      following binding of both heads to actin in the absence of ATP, demonstrating
      that the mutation selectively destroys the initiation of processive runs at
      physiological ATP levels. A drug (omecamtiv) that accelerates the actin-activated
      activity of cardiac myosin was able to rescue processivity of the D179Y mutant
      dimers at physiological ATP concentrations by slowing the actin-independent
      release of Pi. Thus, it may be possible to create myosin VI-specific drugs that
      rescue the function of deafness-causing mutations. 

PMID- 25751915
TI  - [A first prize for Soins Gerontologie].

PMID- 25751916
TI  - [A plan for neurodegenerative diseases].

PMID- 25751917
TI  - [End of life care, report of the CCNE].

PMID- 25751914
TI  - [Abuse, we must all remain vigilant!].

PMID- 25751918
TI  - [Alzheimer disease and apathy].

PMID- 25751913
TI  - [When the unconscious is not infertile].
AB  - Among infertile couples who are undergoing the process of medically assisted
      reproduction, those for whom no biological cause for their infertility has been
      detected are offered a meeting with a liaison psychiatry team. They can then
      continue consultations with a psychiatrist in private practice. These
      consultations confront the couples with the various conflicts, injuries and
      impulses, buried in their unconscious which can cause symptoms of infertility.
      What is at play for these men and women and for the structure of each couple in
      its singularity?

PMID- 25751919
TI  - [Regional roundtable discussions about arthritis].

PMID- 25751925
TI  - [The role of interdisciplinary care in helping the elderly remain independent].
AB  - Frailty constitutes an early stage of dependency, characterising a situation
      which is unstable but which can be reversed if rapid screening is carried out,
      combined with quality, interdisciplinary care. This article presents the example
      of how the elderly are cared for in a residential home.

PMID- 25751921
TI  - [Prevention of cardiovascular diseases: a low sugar diet or a low fat diet?].

PMID- 25751926
TI  - [Health plan and care objectives for frail elderly people living at home].
AB  - With all the assistance put in place to help a person in the process of losing
      their autonomy, why a regression could be observed? Is the care suitably adapted?
      These issues lead private practice nurses to reconsider their care provision, in
      terms of activity, collaboration and organisation, in order to adapt the
      objectives to a specific and complex situation in the context of frailty.

PMID- 25751922
TI  - [Frailty and dependence].

PMID- 25751920
TI  - [Collective campaign against the flu].

PMID- 25751924
TI  - [Taking into account frailty in nursing practice].
AB  - By considering frailty as a clinical syndrome, nurses highlight the decrease in
      physiological reserve capacities which affects a person's coping mechanisms in
      response to stress. Frailty is a risk marker of which age is one of the
      determining factors. Nurses, through their attitudes, reasoning and actions, can
      influence this potentially reversible process.

PMID- 25751928
TI  - [The nurse consultation in the patient's home, essential support].
AB  - The nurse consultation is presented to professionals as a form of opening up and
      discovering in patient care. Home visit nurse practitioners can put this approach
      into practice. This exercise can be easily integrated into their day-to-day work
      with patients.

PMID- 25751929
TI  - [Bibliography. Frailty and dependence].

PMID- 25751923
TI  - [Identifying frailty and delaying dependency].
AB  - As a person ages, frailty and chronic pathologies appear which can restrict their
      level of activity and gradually lead to dependency. Identifying and treating this
      frailty in people aged 65 and over is therefore essential for improving and/or
      maintaining their quality of life.

PMID- 25751927
TI  - [Nutrition and frail elderly at risk].
AB  - Good health for elderly people depends on some extent on their nutritional
      status. During the completion of a master's degree in nursing sciences, a study
      highlighted the need to develop measuring tools for screening for undernutrition
      in the elderly in community nursing practice. A programme for raising awareness
      of the consequences of undernutrition in elderly people is an area to develop
      through broader frailty screening in primary care.

PMID- 25751930
TI  - [The delusional elderly patient, a challenge for caregivers].
AB  - A delusion is any misconception which goes against all evidence to the contrary,
      whether it be an inaugural delusion or whether it occurs with the development of
      dementia. Chronic delusions are distinct from acute delusional expressions, of
      greater or lesser conviction, which are seen as symptomatic productions in
      dementia patients and are sometimes the result of depression. Caregivers should
      be aware of these diseases.

PMID- 25751931
TI  - [Student hospital managers and the provision of care for the elderly].
AB  - During their training in public health care higher education institutes, future
      hospital managers carry out several work placements in health care institutes,
      including one in a geriatric unit. While they often having negative
      preconceptions of this sector, their experience in the departments, in contact
      with the patients/residents and the professionals working there, is the
      opportunity to deconstruct their prejudices and to discover a sector which is
      dynamic, innovative and very rich in human terms. They thereby become aware of
      the specificity of the provision of care for the elderly and the need to
      integrate it into the future strategies of public health institutes.

PMID- 25751932
TI  - [Palliative care during hospitalization].

PMID- 25751933
TI  - [Myocardial infarction in the elderly].

PMID- 25751934
TI  - [Study on traceability system of genuine medicinal materials].
AB  - Genuine medicinal materials with special characteristics of Traditional Chinese
      Medicine (TCM), is recognized as high quality medicine. Both ancient records and
      modern research considered that the origin is an important reason for the
      formation of genuine medicinal materials. However, blindly transplanting of
      genuine medicinal materials has led to the quality decline and counterfeit
      medicines appeared in production or sale progress, which may increase the risk of
      accidents in TCM. Frequent accidents emerged in Chinese herbal affects its
      export. What's more, it is a great threat to the medication safety in TCM
      clinical. There is an urgent need to implement traceability systems of TCM, which
      could provide convenient information record and traceability of TCM circulation.
      This paper reviews a variety of technical methods for genuine medicinal materials
      traceability, and proposed the establishment of genuine medicinal materials
      traceability system based on two-dimensional code and network database.

PMID- 25751935
TI  - [Research progress of adverse reactions of traditional Chinese medicine
      injections].
AB  - Traditional Chinese medicine injections (TCMIs) originated in china, which was
      fast-acting with high bioavailability. TCMI is applied widely in clinic since it
      plays an important role for therapy severe and acute disease, such as
      cardiovascular diseases (CVD), infectious diseases, malignancy, and etc. However,
      the adverse reactions reported of TCMIs are increasing in recent years. For this,
      the review summarized systematically the reports and researches of adverse drug
      reactions (ADRs) of TCMIs according to about 100 literatures in the nearly five
      years. The ADR of TCMIs mainly includes allergic reaction, respiratory damage,
      digestive system damage, cardiovascular system damage and urinary system damage,
      and etc. The main causes are relative with complexity, uncertainty and
      instability of the drug material. Influence of excipients, pharmaceutical
      technologies, drug combination and application method was also discussed. There
      are many methods on adverse reactions of TCMIs, including descriptive studies,
      analytical epidemiology and experimental studies. This article provided necessary
      information for reasonable application of TCMIs in clinical practice.

PMID- 25751936
TI  - [Advances in studies on biotransformation of ginsensides].
AB  - Ginseng saponins are a type of important active substances in the ginseng genus
      plants. They have notable pharmacological activities of antineoplastic,
      neuroprotective, and hepatoprotective activities, which have been drawn more
      attention to obtain minor ginsenosides by all kinds of methods. In this review,
      we discussed the latest progress for enrichment of minor ginsenosides by
      biological transformation of major ginsenosides. At the same time, we have a
      brief outlook of the research at bioconversion of ginseng saponins.

PMID- 25751937
TI  - [Research progress on pharmacology, pharmacokinetics and determination of ergosta
      4,6,8 (14),22-tetraen-3-one].
AB  - Ergosta-4,6,8(14),22-tetraen-3-one (ergone) is one of main components in many
      medicinal fungi. Ergone has been reported to possess the activities of diuresis,
      cytotoxicity, antitumor, immunosuppression, as well as treatment of chronic
      kidney disease. According to reported literatures, an overview of spectroscopy
      characteristics, content determination, pharmacological activity and
      pharmacokinetics, etc. for ergone is presented in this review. Furthermore, the
      present review can provide a certain reference value for the further study and
      development of ergone.

PMID- 25751938
TI  - [Breeding of new Curcuma wenyujin variety "Wenyujin No. 1"].
AB  - In order to breed and spread a new cultivar of Curcuma wenyujin, the C. wenyujin
      germplasm resources were investigated in authentic regions. Better varieties were
      chosen by comparing the yield, economic characters and quality differences
      between different cultivars. The results showed that the character of new
      selected cultivar was stable, the yield of zedoary, turmeric and curcuma was
      reached 313.7, 177.9, 91.2 kg per 667 m2, respectively, it increased 11.6%,
      10.2%, 14.2% comparing with farmer varieties. The volatile oil contents in
      zedoary and turmeric was 4.0%, 3.0%, respectively. The target ingredients
      (germacrone) content was stable. It is demonstrated that the new cultivar
      "Wenyujin No. 1" has value for extension at authentic regions.

PMID- 25751939
TI  - [Growth and developmental rhythm of Scrophularia ningpoensisin southwest middle
      mountain area of China].
AB  - Plant samples were collected and investigated periodically. According to the
      growth of different parts and the characteristics of dry substance accumulation
      of Scrophularia ningpoensis, the development of S. ningpoensis could be divided
      into four stages: seeding stage, stem and leaf growth stage, expanding period of
      root tubers, and dry substance accumulation stage of root tuber. Leaf numbers of
      S. ningpoensis grew gradually from one at first to 370 at the final stage, main
      stem leaf were 50 pieces. Leaf size increasesed with the fastest growth at the
      stem and leaf growth stage, average daily increase amount was 225 cm2. By the
      middle of August, leaf size reached to 16,270 cm2. Leaf area indexrose sharply in
      the seeding stage, and remained above 8 among stem and leaf growth stage and
      expanding period of root tubers, and rapidly reduced to zero in the stage of dry
      substance accumulation of root tuber. Leaf area ratio has a tendency of obvious
      dropping. The net assimilation rate had a small change ranges, two small peak
      were seeding stage and dry substance accumulation of root tuber. The value of
      specific leaf area was higher in seeding stage, and in the earlier stage of dry
      substance accumulation of root tuber. Relative growth rate changed with large
      ranges, higher in seeding stage, rapid decrease in stem and leaf growth stage,
      rose in expanding period of root tubers, and declined again in the stage of dry
      substance accumulation of root tuber. Crop growth rate was higher in the first
      and last stages, and smaller in interim stage. The growth parameters of S.
      ningpoensis such as relative growth rate, net assimilation rate, leaf area index,
      leaf area ratio, specific leaf area, crop growth rate changed along with the
      growth. The rule of dry matter accumulation was as follows: the dry matter
      increased slowly during the seeding stage and speeded up in the middle and late
      stages, and in dry substance accumulation of root tuber increased slower, the
      growth of dry matter all appeared an "S" curve, and accorded with logistic
      equation. Cultivation technologies of S. ningpoensis and the relevant management
      methods could be established according to the growth of different parts of S.
      ningpoensis and the characteristics of dry substance accumulation in different
      stage.

PMID- 25751940
TI  - [Genetic diversity of different populations of lilyturf revealed by RSAP
      analysis].
AB  - Restriction site amplification polymorphism (RSAP) markers were employed to
      access the genetic diversity and relationship of 120 lilyturf germplasms from
      different geographical origins. Sixteen RSAP primer pairs generated 326
      polymorphic bands, of which 318 (97.55%) were polymorphic. The value of
      polymorphism information content (PIC) ranged from 0.87 to 0.95 with an average
      of 0.92. These results indicated there was abundant genetic diversity among
      samples. The results of data analysis on 20 population showed that the value of
      percentage of polymorphic locus (PPL), Nei's gene diversity (H) and Shannon's
      information index (I) were 19.94%-85.58%, 0.082 6-0.210 7, 0.120 6-0.328 1
      respectively. The most abundant genetic diversity was found in the O. japonicus
      population from Zhejiang and the least in the Liriope minor population. The
      genetic distance among 20 population was 0.024 6-0.286 8, of which the minimum
      genetic distance was 0.024 6 between population I and population 13 while the
      maximum 0.286 8 between population 5 and population 15. Coefficient of genetic
      differentiation among natural populations was 0.115 3 (Gst). And the gene
      differentiation contributed to 43.07% of the total genetic variation among
      populations and to 56.93% within populations. The total gene flow (Nm) was 0.660
      9. UPMGA clustering analysis was basically similar to of the principle coordinate
      analysis (PCA). The 120 samples were classified into four major groups, which
      were basically corresponded with the genetic relationships based on morphological
      traits. The results of UPMGA and PCA were also consistent with geographical
      origins.

PMID- 25751941
TI  - [Identification of Dendrobii Caulis basing on ITS sequence].
AB  - Isolation of high-quality genomic DNA from dried and processed crude drug is the
      key for the DNA identification of Dendrobii Caulis. The DNA extract of Dendrobii
      Caulis was firstly compared using different method to isolate genomic DNA from
      dried and processed crude drug, including commercial DNA extracted kit and CTAB
      method. Using modified CTAB method (extracted from large samples), the genomic
      DNA was successfully isolated from Dendrobii Caulis, including Huangcao and
      Fengdou. The ITS regions were amplified using the purified DNA as template, and
      then cloned and sequenced. These ITS sequences were compared with data from
      Genbank database and our lab, 14 Dendrobium species and five similar species were
      identified from "Huangcao" and "Huangcao" slice, while six species and three
      similar species from "Fengdou" according to their sequence similarity. The study
      demonstrated that the dried Dendrobii Caulis could be identified using DNA
      molecular method, which could overcome deficiencies and limitations of
      traditional identification method and has a certain application prospects.

PMID- 25751942
TI  - [Optimization and characterization of curcumin-piperine dual drug loaded self
      microemulsifying drug delivery system by simplex lattice design].
AB  - The objective of the study was to prepare and evaluate the quality of curcumin
      piperinedual drug loaded self-microemulsifying drug delivery system(Cur-PIP
      SMEDDS). Simplex lattice design was constructed using optimal oil phase,
      surfactant and co-surfactant concentration as independent variables, and the
      curcumin and piperine were used as model drugs to optimize Cur-PIP-SMEDDS
      formulation. In the present study, the drug loadings of curcumin and piperine,
      mean particle size of Cur-PIP-SMEDDS were made as indicators, and the experiment
      design, model building and response surface analysis were established using
      Design Expert 8. 06 software to optimize and verify the composition of SMEDDS
      formulation. The quality of Cur-PIP-SMEDDS was evaluated by observing the
      appearance status, transmission electron microscope micrographs and determining
      particle diameter, electric potential, drug entrapment efficiency and drug
      loading of it. As a result, the optimal formulation of SMEDDS was CapryoL 90
      Cremophor RH40-TranscutoL HP (10:60:30). The appearance of Cur-PIP-SMEDDS
      remained clarified and transparent, and the microemulsion droplets appeared
      spherical without aggregation with uniform particle size distribution. The mean
      size of microemulsion droplet formed from Cur-PIP-SMEDDS was 15.33 nm, the drug
      loading of SMEDDS for Cur and PIP were 40.90 mg . g(-1) and 0.97 mg . g(-1),
      respectively, the drug entrapment efficiency were 94.98% and 90.96%,
      respectively. The results show that Cur-PIP-SMEDDS can increase the solubility
      and stability of curcumin significantly, in the expectation of enhancing the
      bioavailability of it. Taken together, these findings can provide the reference
      to a preferable choice of the Cur formulation and contribute to therapeutic
      application in clinical research.

PMID- 25751943
TI  - [Quality evaluation and stability investigation of asarone submicro emulsion
      injection].
AB  - The content of the asarone submicro emulsion injection was determind by HPLC
      method, and thereby a quality evaluation method was established based on indexes
      of pH value, particle size, peroxide value, methoxy aniline values, free fatty
      acid, lysophosphatidylcholine, visible foreign substances, insoluble particle,
      sterility, bacterial endotoxin and impurities, etc. The results showed that the
      injection exhibited uniform physical appearance and all the products were in
      milkwhite liquid. The content of the three batches products were respectively
      102.9%, 100.8%, 97.70% of the labeled amount, with mean particle size of 210-250
      nm, and other indexes all met with the standards. The reserved samples showed no
      obvious change in terms of detection indexes and indicated good stability after
      the accelerated stability test and long-term stability for 12 months. The quality
      evaluation method established in this study could be applied to quality control
      and stability investigation of asarone submicron emulsion injection, which laid a
      basis for further clinical research and application.

PMID- 25751945
TI  - [Study on HPLC fingerprint of Congrong Zonggan capsule].
AB  - HPLC fingerprint of Congrong Zonggan capsule was established in order to provide
      basis for quality evaluation. With acteoside as the reference, HPLC was adopted
      for fingerprint analysis on Congrong Zonggan capsule. The chromatographic
      conditions wereas follows. Waters C18 column (4.6 mm x 150 mm, 5 MUm) was used,
      with methylalcohol-0.1% formic acid as the mobile phase for gradient elution at
      the flow rate of 1.0 mL x min(-1). The detection wavelength was 330 nm, and the
      column temperature was 30  degrees C. This method was highly accurate and
      reproducible. All of the 13 components in tested samples reached the baseline
      resolved peak, and 15 batches of finished products showed the similarity of above
      0.95. The method was accurate and feasible and could be used as a simple and
      effective method to evaluate the quality of the traditional Chinese medicines.

PMID- 25751944
TI  - [Influence of different processed methods on 10 kinds of ginsensides in Panacis
      Quinquefolii Radix].
AB  - The influence on 10 kinds of ginsensides of different processed methods of
      Panacis Quinquefolii Radix was discussed. White Panacis Quinquefolii Radix
      (sliced and dried at -80  degrees C), red Panacis Quinquefolii Radix( steamed,
      sliced and dried at -80  degrees C) and commercial Radix Panacis Quinquefolii
      (dried by electric blast air) processed by different methods. HPLC-PDA-ESI- MS
      method was established before by our team. Ten kinds of ginsenosides of them were
      determined. The content of total ginsenosides were as follow: commercial Panacis
      Quinquefolii Radix > white Panacis Quinquefolii Radix > red Panacis Quinquefolii
      Radix. Compared with white Panacis Quinquefolii Radix, the content of Re, Rc, Rb3
      and Rb2 of Red Radix Panacis Quinquefolii decreased but increased that of Rg,,
      Rb1. Both Rg2 and Rg, were not found in white Panacis Quinquefolii Radix and
      commercial Panacis Quinquefolii Radix by PDA detector, and low response in ESI
      MS, while red Panacis Quinquefolii Radix was to the high content that of 0. 027%
      and 0.040 1%. The constituent of RA0 of red Panacis Quinquefolii Radix was higher
      than the other two. After Panacis Quinquefolii Radix processed, the kind and
      content of ginsensides were significantly changed. The constituent of some kinds
      of ginsensides was increased and some decreased. Rf was not found in all Panacis
      Quinquefolii Radix samples which were consistent with the former documents.

PMID- 25751946
TI  - [Comparison of component from different species of Inonotus obliquus].
AB  - In this paper, water content, mineral element and active ingredient concentration
      on fifteen Inonotus obliquus which comes from all over the world were studied. In
      the aspect of water content, the free water content of Finnish birch was the
      highest, reaching 77.21%, significantly better than that of other strains. The
      free water content of JL04 is the lowest, only 54.6%. The bound water content of
      HLJ01 which from Heilongjiang is the highest, reaching 10. 74% , significant
      differences among other strains. The bound water content of Birch Russia was the
      lowest. In the aspect of mineral element, the calcium content of NBRC9788 was the
      high- est (3.49 mg . g(-1)), significantly better than other strains. The second
      was Finnish birch. The lowest was CX02. The phosphorus content of NBRC9788 was
      the highest (210.12 MUg . g(-1)), significantly superior to other strains. The
      lowest was JL04. In the aspect of active ingredient concentration, the
      triterpenoids content of HLJ01 was highest (23.7 mg . g(-1)), significantly
      better than other strains. It was good strains for biological products research
      and development and then was Finnish birch. The betulin content of MAFF420165 and
      MAFF420308 was low, they were not suitable for production. The polysaccharide
      content of Finnish birch was the highest (9.7%), significantly better than the
      other strains, it is one of the most ideal and good strains to develop
      polysaccharide. The polysaccharide content from MAFF420308 and MAFF420256 was
      1.2%, lower than other strains. We suggest that avoid using these strains in the
      study of polysaccharide product development.

PMID- 25751947
TI  - [Alkaloids from roots and stems of Litsea cubeba].
AB  - A phytochemical investigation on the roots and stems of Litsea cubeba led to the
      isolation of seven isoquinolone alkaloids. By spectroscopic analysis and
      comparison of their 1H and 13C-NMR data with those in literatures, these
      alkaloids were identified as (+)-norboldine (1), (+)-boldine (2), (+)-reticuline
      (3), (+)-laurotetanine (4), (+)-isoboldine (5), (+)-N-methyl-laurotetanine (6),
      and berberine (7), respectively. Among them, 7 was isolated from the genus for
      the first time. The evaluation of these compounds showed weak anti-inflammatory
      activity against NO production in RAW 267.4 and BV-2 cells.

PMID- 25751948
TI  - [Chemical constituents of Euphorbia dracunculoides].
AB  - Sixteen compounds including daphnoretin (1), isofraxidin (2), scopoletin (3),
      kaempferol (4), quercetin (5), guaijaverin (6), astragalin (7), quercetin-3-O
      beta-D-glucopyranoside (8), naringenin-7-O-beta-D-glucopyranoside (9), 5-O
      methylapi- genin-7-O-beta-D-glucopyranoside (10), methyl gallate (11),
      prionitiside A (12), (2S)-2,3-dihydroxypropyl-1,6,8-trihydroxy-3- methyl-9,10-
      dioxoanthracene-2-carboxylate (13), 3,3'-di-O-methyl ellagic acid (14), 3'-O
      methyl-3,4-O,O-metheneellagic acid-4'-O-beta-D- glucopyranoside (15) and 3,4
      methylenedioxy-3'-O-methylellagic acid (16), were isolated from the 70% acetone
      extract of Euphorbia dracunculoides Lam. Among them, compounds 1-3, 6-9, 11, and
      14 were isolated from E. dracunculoides for the first time, and compounds 10, 12,
      13, 15, and 16 were firstly obtained from the genus Euphorbia. Their structures
      were elucidated by spectroscopic analysis, including 1H-NMR, 13C-NMR, and ESI-MS.

PMID- 25751949
TI  - [Study on secondary metabolites of endophytic fungi Penicillium polonicum].
AB  - The PDB culture medium was selected to ferment the endophyte strain, and the
      secondary metabolites of endophytic fungi Penicillium polonicum were studied.
      Combined application of Sephadex LH-20, ODS and HPLC chromatographies over the
      ethyl acetate extract of the fermented culture led to the isolation of 6
      compounds. By spectral methods, the structures were elucidated as [3, 5-dihydroxy
      2-(7-hydroxy-octanoyl)]-ethylphenylacetate (1), (3, 5-dihydroxy-2- octanoyl)
      ethyl phenylacetate (2), (5, 7-di- hydroxy-9-heptyl)-isobenzo pyran-3-one (3), 3
      (hydroxymethyl) 4-(1E)-1- propen-1-yl-(1R, 2S, 5R, 6S)-7-oxabicyclo [4.1.0] hept
      3-ene-2, 5-diol (4), (E)-2-methoxy-3-(prop-1-enyl) phenol (5) and p
      hydroxylphenylethanol (6).

PMID- 25751950
TI  - [Construction of Saccharomyces cerevisiae cell factories for lycopene
      production].
AB  - For microbial production of lycopene, the lycopene synthetic genes from Pantoea
      agglomerans were integrated into Saccharomyces cerevisiae strain BY4742, to
      obtain strain ZD-L-000 for production of 0.17 mg . L(-1) lycopene. Improving
      supplies of isoprenoid precursors was then investigated for increasing lycopene
      production. Four key genes were chosen to be overexpressed, inclu- ding truncated
      3-hydroxy-3-methylglutaryl-CoA reductase gene (tHMG1), which is the major rate
      limiting enzyme in the mevalonate (MVA) pathway, a mutated global regulatory
      factor gene (upc2.1), a fusion gene of FPP synthase (ERG20) and endogenous GGPP
      synthase (BTS1), which is a key enzyme in the diterpenoid synthetic pathway, and
      GGPP synthase gene (SaGGPS) from Sulfolobus acidocaldarius. Over-expression of
      upc2.1 could not improve lycopene production, while over-expression of tHMGI ,
      BTS1-ERG20 and SaGGPS genes led to 2-, 16. 9- and20. 5-fold increase of lycopene
      production, respectively. In addition, three effective genes, tHMG1, BTS1-ERG20
      and SaGGPS, were integrated into rDNA sites of ZD-L-000, resulting in strain ZD-L
      201 for production of 13.23 mg . L(-1) lycopene, which was 77-fold higher than
      that of the parent strain. Finally, two-phase extractive fermentation was
      performed. The titer of lycopene increased 10-fold to 135.21 mg . L(-1). The
      engineered yeast strains obtained in this work provided the basis for
      fermentative production of lycopene.

PMID- 25751951
TI  - [Study on quality standard for Humulus scandens].
AB  - To control the quality of Humulus scandens, the quality standard was established
      in this study. According to the method recorded in the Appendix of Chinese
      Pharmacopoeia (2010 Edition) , the water and ash inspections were carried out.
      The component luteoloside and cosmosiin in Humulus scandens were identified and
      assayed by TLC and HPLC. The results showed a strong characteristics microscopic
      of Humulus scandens, and trichoromethane-methanol-formic acid (10: 3: 0. 3) as
      the mobile phase of TLC, the spots at 365 nm with a UV lamp was clear. The 16
      batches of samples were analyzed by HPLC with a gradient elution of acetonitrile
      and phosphate solution (0.2%) at a flow rate of 1.0 mL . min(-1) and detected at
      350 nm. The content of luteoloside was 0.015%- 0.651% (average 0.148%); the
      content of cosmosiin was 0.003%-0.118% (average 0.036%). The linear calibration
      curve of luteoloside and cosmosiin was acquired in the ranges of 0.011-0.364 g .
      L(-1) (r = 1.000 0) and 0.003-0.096 g . L(-1) (r = 1.000 0), respectively. The
      average recovery was 100.5% and 98.5%, respectively. The methods are convenient
      and reliable, which can be ap- plied for quality assessment of Humulus scandens.

PMID- 25751952
TI  - [Study on quality assessment of Polygalae Radix based on HPLC-DAD fingerprint].
AB  - OBJECTIVE: To establish an HPLC fingerprint to evaluate the quality of Polygalae
      Radix, root xylem, and those collected in different growth ages or harvest time.
      METHOD: Separation was performed at 30  degrees C on a Kromasil C18 column (4.6
      mm x 250 mm, 5 MUm); the mobile phases was acetonitrile and 0.05% H3PO4 water in
      the gradient elution; the flow rate was set at 1.0 mL . min(-1) and the detection
      wavelength at 314 nm; the quality discriminant analyses were accomplished by
      means of similarity analysis, cluster analysis, principal component analysis and
      neural network model. RESULT: In 26 batches of Polygalae Radix, 24 batches
      fingerprint similarities were above 0.8. In 5 different growth or harvest time
      batches, 4 batches were above 0.8; in 8 batches root xylem samples, the
      similarities were all above 0.875. The similarity analysis was in accord with the
      quality discriminant analysis of cluster analysis, principal component analysis
      and neural network model. CONCLUSION: Fingerprint combined with chemical pattern
      recognition technique can effectively evaluate the quality of Polygalae Radix.
      The active substance species are all similar in cultivated, wild, different
      growth or harvest time Polygalae Radix and polygala root xylem, but the
      chromatography peak areas are different. The effective material contents are
      similar between wild and cultivated Polygalae Radix, but each chromatographic
      peak area of the root xylem is much smaller than that of Polygalae Radix. The
      chemical substance accumulation mainly depends on harvest month, but little
      growth time in Polygalae Radix.

PMID- 25751953
TI  - [Determination and analysis of heavy metals content in Panax notoginseng of
      different origination].
AB  - Six heavy metals, including As, Cu, Hg, Cd, Pb and Cr in Panax notoginseng were
      determined by inductively coupled plasma atomic emission spectrometry (ICP-AES)
      combined with wet digestion method. The samples of P. notoginseng were collected
      in 12 different regions, including Yunnan and Guangxi Province. Green Standards
      of Foreign Trading Medicinal Plants & Preparations was used as the standard to
      evaluate the pollution status of As, Cu, Hg, Cd, Pb and Cr in P. notoginseng. The
      results showed that content of As and Cd exceeded the limit of the standard and
      the percentage was 32.4% and 29.7%, respectively, while Cu, Hg and Pb were all
      bellow the limit. The SPSS 16.0 software was used to analyze the data. The
      occurrence of contained heavy metals has been discussed.

PMID- 25751954
TI  - [Study on effect and mechanism of cinnabaris and realgar in promoting awake of
      endotoxin-induced brain injury rat applied with Angong Niuhuang Wan].
AB  - OBJECTIVE: To explore the effect and mechanism of cinnabaris and realgar in
      promoting awake effect of endotoxin- induced brain injury rat applied with Angong
      Niuhuang Wan. METHOD: Normal rats implanted cortical electrode in advance were
      divided into 6 groups: control, model, the Angong Niuhuang Wan (AGNH, 0.4, 0.2 g
      . kg(-1)), the Angong Niuhuang Wan without cinnabaris and realgar (QZX-AGNH,
      0.32, 0.16 g . kg(-1)). Rats in the control and model groups were given distilled
      water. After three days of intragastric administration, the brain injury model
      was injected with endotoxin through tail vein. Then trace electro-corticogram
      (EcoG) 1-6 h after LPS injection, and compare the power and relative power of
      beta (beta) and delta-waves (delta) at 6 h of these groups. The content of
      acetylcholine (Ach) and the affinity of M-receptor (M-R) in cortex and brainstem
      were detected by alkaline hydroxylamine colorimetric method and radioactive
      ligand binding assay, respectively. RESULT: AGNH (0.4, 0.2 g . kg(-1)) could
      increase the power and relative power of beta and AGNH (0.4 g . kg(-1)) showed
      better action on brain electrical activation. QZX-AGNH showed weak effect on it.
      AGNH (0.4 g . kg(-1)) could increase the affinity of M-R in cortex and the
      content of Ach in brainstem. The action of QZX-AGNH was not obvious. CONCLUSION:
      In endotoxin-induced brain injury rats, AGNH can raise the cholinergic system
      function of cortex, and strengthen the uplink of cortex activation of brainstem
      cholinergic system, improve the level of cortical activity and enhance the
      activation of EcoG to promote the body's awakening. QZX-AGNH show weak effect.
      Cinnabaris and realgar play an important role in promoting awake effect in
      endotoxin-induced brain injury applied with Angong Niuhuang Wan. The mechanism
      may be related to cortical and brainstem cholinergic system function.

PMID- 25751955
TI  - [Evaluation on efficacy-toxicity correlation of aqueous extracts from Aconiti
      Lateralis Radix Praeparata on diarrheal model rats based on "warmly invigorating
      spleen Yang" efficacy].
AB  - The diarrheal rat model was established by orally administering senna. The
      preventive experiment was concurrent for 6 days. The treatment experiment
      modeling had lasted for 12 days. The administration started at the 7th day, and
      lasted for 6 days. During the experiment, efforts were made in symptom score and
      weighing. After the experiment, hearts, livers, spleens, kidneys, brains,
      adrenals and thymuses were collected and weighed, lactic dehydrogenase (LDH) and
      cardiac troponin-I (cTn-I) in serum were detected. The efficacy of
      aqueousextracts from Aconiti Lateralis Radix Praeparata in preventing and
      treating rats with diarrheal and its accompanying toxicity were respectively
      studied. The result shows that aqueous extracts from Aconiti Lateralis Radix
      Praeparata could improve syndromes of rats with diarrheal. The 50% effective
      doses (ED50) of preventive and treatment administrations were 1.420 4 g . kg(-1)
      and 1.048 9 g . kg(-1), respectively. Aqueous extracts from Aconiti Lateralis
      Radix Praeparata could decrease the ratio of heart to body weight, and increase
      serum LDH and cTn-I. It was concluded that aqueous extracts from Aconiti
      Lateralis Radix Praeparata had a specific preventive and treatment effect on rats
      with diarrheal caused by senna, but with specific toxicity on heart.

PMID- 25751956
TI  - [Mechanism of tonifying Qi traditional Chinese medicines contained in Yiqi
      Qingwen Jiedu mixture against influenza immune inflammatory injury].
AB  - OBJECTIVE: To observe the impact of tonifying Qi traditional Chinese medicines
      contained in Yiqi Qingwen Jiedu mixture on mRNA expression of lung inflammatory
      cytokines and pulmonary pathological injury of mice infected by influenza virus,
      in order to discuss the mechanism of tonifying Qi traditional Chinese medicines
      against pulmonary immune inflammatory injury of infected mice. METHOD: In
      different time phases after mice were infected with influenza virus FM1, the RT
      PCR method was adopted to observe the impact of tonifying Qi traditional Chinese
      medicines contained in Yiqi Qingwen Jiedu mixture on five inflammatory cytokines
      TNF-alpha, IL-1, IL-6, IL-10 and IFN-gamma, and the changes in pulmonary
      pathological injury of mice with viral pneumonia after intervention with
      tonifying qi traditional Chinese medicines. RESULT: (1) Tonifying Qi traditional
      Chinese medicines significantly reduced the mRNA expression of TNF-alpha at 1-5 d
      and IL-1 mRNA expression at 7 d, may increase IL-1 mRNA expression in mouse lung
      at 3 d, significantly reduced IL-6 mRNA expression in mouse lung and increased IL
      10 mRNA expression at 3-7 d, and significantly increased IFN-gamma mRNA
      expression at 1 d. (2) Tonifying Qi traditional Chinese medicines could
      significantly inhibited and repaired pulmonary immune inflammatory injury of mice
      infected by FM1, which was most remarkable at 3-7 d after the infection with
      influenza virus FM1. CONCLUSION: Tonifying Qi traditional Chinese medicines
      contained in Yiqi Qingwen Jiedu mixture could resist pulmonary immune
      inflammatory injury and repair inflammatory injury by regulating the mRNA
      expression of imbalance inflammatory cytokines of organisms infected with
      influenza virus.

PMID- 25751957
TI  - [Effects of soothing liver and invigorating spleen recipes on LPS-induced
      hepatocytes injury of rats and TLR4/p38MAPK signal pathway].
AB  - OBJECTIVE: To explore the effects of soothing liver and invigorating spleen
      recipes on lipopolysaccharide(LPS) induced hepatocyte inflammation of rats and
      TLR4/p38MAPK signal pathway. METHOD: The hepatocytes of SD rats were cultured and
      identified in vitro. The medicated serum of soothing liver and invigorating
      spleen recipes was prepared. The hepatocytes were treated with soothing liver and
      invigorating spleen recipes. Then Interleukin-6 (IL-6) and tumor necrosis factor
      alpha (TNF-alpha) expression in cultural supernatants were assayed by ELISA. The
      expressions of Toll-Like 4 (TLR4), p38 mitogen activated protein kinases
      (p38MAPK) and p-p38 mitogen-activated protein kinase (p-p38MAPK) were detected by
      Western blot. RESULT: The rat medicated serum of soothing liver and invigorating
      spleen recipes was extracted for 2-3 mL. The purified rat hepatocytes were 1.5 x
      10(8)-2.0 x 10(8). The cell viability was above 95% detected by Typan blue
      staining. The hepatocytes were identified by immumofluorescence assay. The
      detection of hepatocyte cultural supernatants: compared with that of the control
      group, IL-6 and TNF-alpha expression were increased in the LPS group (P < 0.01).
      While compared with that of the LPS group, the expressions of IL-6 and TNF-alpha
      were decreased after soothing liver and invigorating spleen recipes intervention
      (P < 0.01). The detection of hepatocyte proteins: compared with that of the
      control group, the protein expressions of p38MAPK, p-p38MAPK and TLR4 were all
      increased significantly in the LPS group (P < 0.01). Compared with that of the
      LPS group, the protein expressions of p38MAPK was decreased significantly in
      SB239063 group and it was also decreased in the soothing liver and invigorating
      spleen recipes group, but with no significant difference. Compared with that of
      the LPS group, p38MAPK expression was reduced significantly in the soothing liver
      and invigorating spleen recipes group and the SB239063 (p38MAPK pathway
      inhibitor) group (P < 0.01). TLR4 protein expression was decreased markedly in
      the soothing liver and invigorating spleen recipes group (P < 0.01) but had no
      difference between the SB239063 group and the LPS group. CONCLUSION: The soothing
      liver and invigorating spleen recipes may regulate hepatocyte inflammatory injury
      of rats through TLR4/p38MAPK signaling pathway.

PMID- 25751958
TI  - [Effects of various compounds on efficacy of artemisinin in a yeast model].
AB  - Artemisinin is a key anti-malarial drug and few clinically meaningful resistant
      cases about its application have so far been reported. The World Health
      Organization (WHO) officially recommended the use of ACT (Artemisinin-based
      Combination Therapy) as the first line antimalarial application to increase its
      inhibitory efficacy and prevent the likely resistance development. Based on our
      current understanding of artemisinin, a set of compounds were selected to study
      their interaction with artemisinin by using the yeast (S. cerevisiae) model, in
      the hope that knowledge gained might provide some references for clinical
      investigations. In this research, yeast strain (BY4742) was cultured in the
      nonfermentable YPGE solid medium with 4 MUmol . L(-1) artemisinin and one of the
      selected compounds for 48 hours, and the combined drug efficiency was evaluated
      by the inhibition of yeast growth. The compounds belong to the categories of
      oxygenants, antioxidants, metal ions, ion chelators and uncouplers. Among them,
      0.2 mmol L(-1) FeCl3, 60 MUmol . L(-1) BPS, 1 mmol . L(-1) CuCl2, 0.75 mmol . L(
      1) VE and 1 mmol . L(-1) VC antagonized the action of artemisinin, while 40 MUmol
      . L(-1) DNP, 0.1 MUmol . L(-1) CCCP and 0.25 mmol . L(-1) H2O2 had synergistic
      effects. These results suggested that redox-active and mitochondria-dysfunctional
      compounds could affect artemisinin's potency, supporting our prior proposed
      mitochondrial model for artemisinin's action. This research in addition provided
      a convenient method to screen likely artemisinin-interacting compounds.

PMID- 25751959
TI  - [Experimental study on effect of allicin in inhibiting insulin-induced vascular
      smooth muscle cell proliferation and migration].
AB  - OBJECTIVE: To investigate the effect of allicin in inhibiting insulin-induced
      vascular smooth muscle cell (VSMC) proliferation and migration. METHOD: The
      tissue explant method was adopted to culture rat's aVSMCs, and the
      immunofluorescence method was used to identify alpha-SMA. Cells from the third to
      fifth generations were selected in the experiment The insulin-induced VSMC model
      was established. The experiment was carried out in five groups: the control
      group, the insulin group, the allicin group, the ERK inhibitors PD98059 group (20
      MUmol . L(-1)) and the PD98059 + allicin group. VSMCs' proliferation was
      determined by CCK8 colorimetric method, while its migration was detected by cell
      counting; The western blotting was used to detect total ERK, Phospho-ERK, PCNA
      protein's expression. RESULT: Primary cultured VSMCs grew well in the spindle
      shape under the lightmicroscope, with peak and valley. alpha-SMA
      immunofluorescence results showed that the cultured cells had typical VSMCs'
      features. Insulin could stimulate VSMCs' proliferation and migration, with the
      best effect at the concentration of 100 nmol . L(-1). The pretreatment with
      allicin could significantly inhibit VSMCs' proliferation and migration induced by
      insulin in a dose-dependent manner. The pretreatment with PD98059 and allicin +
      PD98059 could inhibit VSMCs' proliferation and migration induced by insulin
      remarkably as well. Insulin could significantly accelerate VSMCs' expression of
      such proteins as p-ERK, PCNA. Contrarily, allicin could notably inhibit VSMCs'
      expression of such proteins as p-ERK, PCNA in a dose-dependent manner.
      CONCLUSION: Allicin could significantly inhibit VSMCs' proliferation and
      migration induced by insulin, which may be related to the inhibition of the
      activation of ERK signal path.

PMID- 25751961
TI  - [Dynamic monitoring risk of anti-hepatoma new drug development].
AB  - Risk monitoring of new Chinese patent anti-hepatoma drugs is tracking recognized
      risks and residual risks, identifying emerging risk and ensure the implementation
      of the plan, estimating the process of reducing effectiveness. The paper is
      mainly through understanding the status of Chinese patent anti-hepatoma drugs,
      the content, characteristic and analysis method of dynamic risk monitoring, and
      then select the risk control indicators, collect risk information. Finally, puts
      forward the thought of anti-hepatoma drugs listed evaluation in our country, and
      try to establish the model of dynamic risk management of anti-hepatoma drugs.

PMID- 25751960
TI  - [Role of PI3K/Akt pathway in effect of paeoniflorin against Abeta25-35-induced
      PC12 cell injury].
AB  - OBJECTIVE: To study the role of PI3K/Akt pathway in the neuroprotective effect of
      paeoniflorin on PC12 cells. METHOD: The paeoniflorin group (5, 10, 20 MUmol . L(
      1)) was pretreated for 30 min, and then added with Abeta25-35 (20 MUmol . L(-1))
      for interaction for 24 h. Inhibitor LY294002 (10 MUmol . L(-1)) was pretreated
      for 30 min before the action of paeoniflorin (10 MUmol . L(-1)). The MTT
      colorimetric method was used to detect the cell viability. The apoptosis rate was
      tested by the FITC-Annexin V/PI staining. The protein expression of p-AKT, Bax,
      Bcl-2 and cleaved caspase-3 protein were detected by Western blot analysis.
      RESULT: Paeoniflorin could significantly inhibit the Abeta25-35-induced PC12 cell
      toxicity and apoptosis. Its protection effect may be achieved by up- regulating
      AKT phosphorylation level, increasing Bcl-2 protein expression, reducing Bax
      protein expression, inhibiting the activation of caspase-3. Inhibitor LY294002
      could weaken the above protective effects of paeoniflorin. CONCLUSION:
      Paeoniflorin could activate PI3K/Akt signaling pathway to protect the PC12 cell
      injury induced by Abeta25-35.

PMID- 25751962
TI  - [Discussion of anti-inflammatory mechanism of cyclooxygenase (COX-2) inhibitor in
      improving cardiovascular safety].
AB  - The new generation cyclooxygenase (COX-2) inhibitor could reduce the
      gastrointestinal side effect of NSAID drugs, but eventually increase the
      cardiovascular risk, because its selective inhibition of COX-2 induces the
      imbalance between PGI2 and TXA2 and the reduction of vasodilatory NO. Under
      pathological conditions, active oxygen species (O2-*2, etc) were used to induce
      endo- thelial dysfunction, activate NF-kappaB to induce expressions of pro
      inflammatory cytokines IL-1beta and TNF-alpha, increase ET-1, TXA2 with
      vasoconstrictor effect, reduce PGI2 and NO with vasodilatory effect, generate
      further oxidative damage together with NO, and reduce the bioavailability of NO.
      NO-NSAIDs and NO-Coxibs drugs raised the level of NO by introducing NO-donor
      (ONO2). NSAIDs drugs enhanced the anti-inflammatory activity of COX-2 and reduced
      gastrointestinal side effects by inhibiting selectively COX-2. If antioxidant
      structures with active ingredients of traditional Chinese medicines were
      introduced to improve the antioxidant activity of NSAIDs, they could scavenge the
      active oxygen species to protect the normal function of vascular endothelia and
      enhance the bioavailability of NO, which is conducive to enhance the
      cardiovascular safety of cyclooxygenase (COX-2) inhibitor.

PMID- 25751963
TI  - [Mathematical exploration of essence of herbal properties based on "Three
      Elements" theory].
AB  - Herbal property theory of traditional Chinese medicines is the theoretical
      guidance on authentication of medicinal plants, herborization, preparation of
      herbal medicines for decoction and clinical application, with important
      theoretical value and prac- tical significance. Our research team proposed the
      "three-element" theory for herbal properties for the first time, conducted a
      study by using combined methods of philology, chemistry, pharmacology and
      mathematics, and then drew the research conclusion that herbal properties are
      defined as the chemical compositions-based comprehensive expression with complex
      and multi-level (positive/negative) biological effects in specific organism
      state. In this paper, researchers made a systematic mathematical analysis in four
      aspects--the correlation between herbal properties and chemical component
      factors, the correlation between herbal properties and organism state fac- tor,
      the correlation between herbal properties and biological effect factor and the
      integration study of the three elements, proposed future outlook, and provided
      reference to mathematical studies and mathematical analysis of herbal properties.

PMID- 25751964
TI  - [Establishment of industry promotion technology system in Chinese medicine
      secondary exploitation based on "component structure theory"].
AB  - The purpose of the secondary exploitation of Chinese medicine is to improve the
      quality of Chinese medicine products, enhance core competitiveness, for better
      use in clinical practice, and more effectively solve the patient suffering.
      Herbs, extraction, separation, refreshing, preparation and quality control are
      all involved in the industry promotion of Chinese medicine secondary exploitation
      of industrial production. The Chinese medicine quality improvement and industry
      promotion could be realized with the whole process of process optimization,
      quality control, overall processes improvement. Based on the "component structure
      theory", "multi-dimensional structure & process dynamic quality control system"
      and systematic and holistic character of Chinese medicine, impacts of whole
      process were discussed. Technology systems of Chinese medicine industry promotion
      was built to provide theoretical basis for improving the quality and efficacy of
      the secondary development of traditional Chinese medicine products.

PMID- 25751965
TI  - [Exploration of influencing factors of price of herbal based on VAR model].
AB  - Based on vector auto-regression (VAR) model, this paper takes advantage of
      Granger causality test, variance decomposition and impulse response analysis
      techniques to carry out a comprehensive study of the factors influencing the
      price of Chinese herbal, including herbal cultivation costs, acreage, natural
      disasters, the residents' needs and inflation. The study found that there is
      Granger causality relationship between inflation and herbal prices, cultivation
      costs and herbal prices. And in the total variance analysis of Chinese herbal and
      medicine price index, the largest contribution to it is from its own
      fluctuations, followed by the cultivation costs and inflation.

PMID- 25751966
TI  - Informing and involving the nursing community.

PMID- 25751967
TI  - Early isolation of patients critical.

PMID- 25751968
TI  - Mice strains offer genetic clues.

PMID- 25751969
TI  - Antimicrobial copper's potential.

PMID- 25751970
TI  - Disinfectant to go.

PMID- 25751971
TI  - Respiratory vaccine shows promise.

PMID- 25751972
TI  - Ebola by the numbers.

PMID- 25751974
TI  - National case definition: Ebola virus disease (EVD) (under revision).

PMID- 25751973
TI  - MSF in West Africa.

PMID- 25751975
TI  - Statement on infection prevention and control measures for Ebola virus disease
      (December 2014).

PMID- 25751976
TI  - Public health management of cases and contacts of human illness associated with
      Ebola virus disease (EVD) (under revision).

PMID- 25751978
TI  - How we are preparing for Ebola.

PMID- 25751977
TI  - "Safety is not negotiable".

PMID- 25751979
TI  - The SARS experience.

PMID- 25751981
TI  - Infection prevention and control quiz.

PMID- 25751980
TI  - Planning for the psychosocial aspects of EVD.

PMID- 25751983
TI  - Hu-Friedy 77R--a handy tool.

PMID- 25751984
TI  - Polyethylene microbeads?

PMID- 25751985
TI  - Soda makers' pledge smaller sizes, less sugar. Effort might help reduce tooth
      decay. .

PMID- 25751986
TI  - Wired or wireless networking?

PMID- 25751994
TI  - Facebook advertising: 5 Tools dental practices must use to generate results.

PMID- 25751996
TI  - Anesthesia committee revising requirements to be in line with ADA guidelines.

PMID- 25751997
TI  - The joy of life.

PMID- 25752003
TI  - Strengthening overall health through education.

PMID- 25752008
TI  - [Networks of postgraduate education: a tool for regulating the number of
      specialists?].

PMID- 25752009
TI  - [Shoulder arthroplasty: the situation in 2014].
AB  - Evolution of shoulder arthroplasty has led to mainly three types of implants:
      hemiarthroplasty, total shoulder arthroplasty and reverse shoulder arthroplasty.
      There is yet no clear consensus about indications for the different existing
      types of prothesis. The aim of this article is therefore to bring together and
      clarify the indications found in the current literature. Hemiarthroplasty,
      historically the first widely used implant, has lost much ground to total
      shoulder arthroplasty, and keeps its place only for specific situations. Total
      shoulder arthroplasty is mainly used for centered glenohumeral osteoarthritis,
      whereas reverse shoulder arthroplasty is indicated for most situations in which
      the rotator cuff or tuberoties are deficient.

PMID- 25752010
TI  - [Management of malignant bone tumors around the knee].
AB  - Primary bone tumors arise mostly around the knee. A treatment strategy issued
      from a multidisciplinary team is the key factor for an optimal management of such
      patients. Many durable options for reconstructing a functional limb are
      available, as an alternative to amputation, without lowering patients' survival.
      Nevertheless complications are frequent and any decision for one technique or the
      other should be made with the patient, appreciating the specificity of each
      single case. We discuss here the different techniques with their advantages and
      drawbacks, including long term results.

PMID- 25752011
TI  - [Lower limb amputation: indication, preoperative workup and complications].
AB  - The main causes of lower limb amputations are peripheral artery disease (92% of
      the cases) and trauma (7%). The selection of the amputation level aims at
      optimizing the chances of healing and the functionality of the involved limb.
      Foot preserving amputations offer the best functional outcome but the healing
      process is frequently slow and difficult. After a below-knee amputation, 60% of
      the patients are capable of ambulating again, whereas only 20% of the patients
      undergoing an above-knee amputation ambulate autonomously. Complications after
      amputations are frequent, can occur a long time after surgery and must be managed
      by a highly specialized team.

PMID- 25752012
TI  - [Periprosthetic fractures].
AB  - A periprosthetic fracture is a fracture around or in proximity of a prosthetic
      implant. As more and more prostheses are implanted, the incidence of
      periprosthetic fractures also increases. Several risk factors have been outlined,
      some due to the patient, and some due to the implant itself. Key points in
      diagnosis are the case history and the imaging, as they allow the distinction
      between a well-fixed and a loose prosthesis. Correct classification is crucial
      for the treatment choice, which can be non-operative or consist in an
      osteosynthesis or in a revision arthroplasty, depending on the patient's general
      medical condition and the local status.

PMID- 25752013
TI  - [Ankle fractures in the elderly patient].
AB  - Ankle fractures in adults are usually managed by open reduction internal
      fixation. In elderly patients the surgical dilemma relates to bone quality.
      Osteoporosis is the enemy of internal fixation, and secure purchase of screws in
      osteopenic bone may be difficult to achieve. Insufficient screw purchase may lead
      to loss of reduction, wound breakdown, and infection. Postoperative management
      after osteosynthesis usually requires an extended period of restricted weight
      bearing. However, this is not feasible in older patients as a result of their
      lack of strength in the upper extremities and frequent comorbidities. Therefore,
      augmen- ted methods of internal fixation and specific surgical techniques have
      been developed using metal and bone cement. This permits this fragile population
      to begin early full weight bearing in a removable brace.

PMID- 25752014
TI  - [Single use custom made instrumentation, the future of total knee arthroplasty?].
AB  - It is expected that the number of total knee arthroplasties should be multiplied
      by 7 in twenty years. Until now, this procedure required a large number of
      surgical trays. Three-dimensional preoperative planning, persona-lized cutting
      guides, and disposable instrumentation kits can now help to optimize this
      procedure by providing a unique single-use surgical kit per patient. This type of
      instrumentation leads to improvements in precision, operative time, turnover
      time, sterilization and maintenance costs, and could help reduce infectious
      risks. This technology is a step towards personalized orthopedic surgery, and
      opens new perspectives on a future with implants entirely customized for each
      patient.

PMID- 25752015
TI  - [Statin treatment in primary and secondary prevention--a statement].
AB  - Although lipid-lowering therapy in patients with established coronary heart
      disease (secondary prevention) is generally accepted, its benefit is often
      questioned in asympto- matic patients. The ongoing debate about the usefulness of
      statin therapy has disturbed many patients, especially in the French- and Italian
      speaking parts of Switzerland, which lead too often to treatment discontinuation,
      even in patients who would benefit the most from it. In the primary prevention,
      the reduction in LDL cholesterol levels with statins decreases the risk for
      cardiovascular events. The higher the baseline risk, the greater the benefits in
      terms of absolute risk reduction; hence, using a scoring tool to evaluate the
      cardiovascular risk is needed. For patients at low risk, lifestyle interventions
      are preferable.

PMID- 25752016
TI  - [Removal of organs: France joins the countries authorizing cases "Maastricht
      III"].

PMID- 25752017
TI  - [Policy based evidence-making].

PMID- 25752018
TI  - [Ebola: Note MSF on the epidemiological situation in West Africa].

PMID- 25752019
TI  - [Acamprosate and naltrexone: similar efficacy for relapse].

PMID- 25752020
TI  - [By the prefectural decree, it is forbidden to light fires in the fireplaces of
      Paris].

PMID- 25752022
TI  - [Complementary medicine are offered at the CHUV].

PMID- 25752023
TI  - [Life at the other end].

PMID- 25752021
TI  - [Valais centralizes its hospital service supply].

PMID- 25752025
TI  - [Collisional relaxation between highly vibrationally excited Na2 and Ar and H2].
AB  - Energy transfer rate constants were measured for excited rovibrational levels of
      Na2 (X1Sigma(g)+). Stimulated emission pumping was used to excited the levels v =
      33-51, J = 11 via A-X transition. Laser induced fluorescence was used to follow
      the collision dynamics. Energy transfer processes induced by collisions with Ar
      and H2 were investigated. The decay curves for the parent level populations gave
      good fits to single exponential function. At v = 33-51, the total transfer rate
      constants increase linearly with vibrational quantum number. Parameterized
      expressions for the (48, 11)--to--(47, J) rate constants were fitted to the
      fractional populations of the satellite lines. This produced sets of relative
      rate constants. Absolute rate constants were then obtained by normalizing the
      sums of the relative rate constants to the total removal rate constants. For Na2
      (v) + Ar, no multiquantum vibrational transfer was detected. For Na2 (v) + H2, a
      significant fraction of the initial population of highly vibrationally excited
      Na2 (X v = 48) relaxes to lower vibrational level (Delta v = -5). The time scale
      is much shorter than the known collisional lifetimes of the intervening
      vibrational levels and thus a sequential single-quantum relaxation mechanism can
      be explicitly ruled out. For v = 48, at least 40% of the initially prepared
      population, undergoes multiquantum vibrational relaxation. We discuss possible
      explanations of this result.

PMID- 25752024
TI  - [Measurement and application of CO2 spectroscopic parameters near 2.0 MUm].
AB  - The accuracy of absorption spectral parameters is very important for the trace
      gas measurement based on absorption spectroscopy techniques, especially for the
      isotopic abundance measurement of gas molecules. For some of the applications,
      spectral parameters listed in HITRAN database were used to retrieve the trace gas
      concentration. However, these parameters have uncertainty, in order to validate
      spectroscopic parameters near 2.0 MUm of CO2 lines, which are to be used in
      detecting the CO2 concentration and isotopic abundance, spectra of those lines
      were recorded at room temperature using a distributed feed-back (DFB) diode
      laser. The recorded absorption spectra were fitted to Voigt profile. Line
      position, intensity, self-broadening coefficient and N2-broadening coefficient
      were deduced from those data. The results show a good consistency in comparison
      with those listed in HITRAN2012 database. The discrepancy of most line
      intensities and self-broadening coefficients are less than 2%. The CO2
      concentration and Delta(13 CO2 ) in real atmosphere inside laboratory are 440 ppm
      and -9 per hundred respectively. These results provide a reliable basis for real
      time and on line detecting the CO2 concentration and Delta(13 CO2) in the
      wavelength range.

PMID- 25752026
TI  - [Structural, morphological and optical properties of PbI2 thick films].
AB  - In the present paper, the structural, morphological and optical properties of
      PbI2 thick films prepared by close-spaced sublimation technique were
      investigated. It was found that the thickness of PbI2 films decreased from 1 000
      MUm to 220 MUm with the increase in the sublimation source temperature. X-ray
      diffraction (XRD) pattern shows that the thick films are polycrystalline
      hexagonal structure with preferred growth orientation of (002) plane, and their
      grain size, dislocation density and growth stress are closely related to the
      source temperature. Images of scanning electron microscopy (SEM) reveal the
      accumulation of hexagonal plate-like particles which constitute the samples, and
      the particles with a diameter of 248 MUm and a thickness of 32.7 MUm, exhibit
      clearly layered structure. By spectrum fitting using Gauss function, the Raman
      spectra show a shift of about 147, 169, 217 and 210 cm(-1) respectively, the
      first three peaks correspond to the longitudinal optical vibrations (LO) mode in
      4H-PbI2 crystal, while the last peak originate from a vibration pattern
      associated with SnO2 in substrate. Raman peak of 147 cm(-1) changes significantly
      with the increases in source temperature, and a dramatic decrease in peak
      intensity with broadening peak width occurred when the source temperature
      increased up to 225 degrees C or more. Under 340 nm excitation at room
      temperature, several weak photoluminescence peaks of PbI2 samples which
      associated with defects and exciton recombination near 2.25, 2.57 and 2.64 eV
      were observed. Given a comprehensive consideration of structural and spectral
      characterization results, PbI2 thick films with a thickness of about 659 MUm
      deposited at a source temperature of 200 degrees C achieves the best crystalline
      quality.

PMID- 25752027
TI  - [Nondestructive evaluation of wheat quality using terahertz time domain
      spectroscopy].
AB  - Terahertz time-domain spectroscopy (THz-TDS) is used to investigate the spectra
      properties of the wheat kernel with various deterioration degrees in the
      frequency range of 0.2-1.6 THz. The absorption coefficient and refractive index
      of normal, worm-eaten, moldy and sprouting wheat kernel were calculated.
      Comparison of the experimental data, clearly indicates that changes in the
      absorption coefficient and refractive index are recorded, different wheat samples
      have different optical parameters. The absorption coefficient of normal wheat
      sample is more obvious and higher than others; refractive index increases as the
      frequency increases. THz-TDS can be employed to evaluate the quality of wheat
      kernel nondestructively. The results show that THz-TDS is a promising and new
      experimental method for quality analyses and control for agricultural production
      detection. This study will provide an important guidance for nondestructive
      detecting the quality of stored-grain.

PMID- 25752029
TI  - [IM/FM phase delay time measurement method of laser for TDLAS].
AB  - The present paper presents an method of using fiber Michelson interferometer to
      measure the Intensity-frequency (IM/FM) phase delay change of the laser, it could
      realize the phase delay time measurement, while modulating the laser.
      Experimental results show that the laser output signal intensity-frequency
      (IM/FM) phase delay of the laser has some differences from the theoretical value.
      The proposed method can be used to compensate for real-time signal strength
      frequency (IM/FM) phase delay effect on the gas concentration measurement
      results.

PMID- 25752028
TI  - [Study of the last glacial loess-like deposits in the coastal area of South China
      with diffuse reflectance spectroscopy and laser particle size analysis].
AB  - Newly discovered yellow silt widely distributed in the coastal area of south
      China was analyzed using diffuse reflectance spectroscopy (DRS) and laser
      particle size (LPS) methods in the present paper. The authors take the lead in
      trying to synthetically judge the depositional environment, transporting agent
      and forming mechanism of the yellow silt from angles of output forms of iron
      minerals as well as grain size distribution features of the samples chose from
      three representative sections and a drill core. The DRS first derivative curves
      show the peak height of iron minerals decreasing from hematite (565 nm) to
      goethite (505 and 435 nm), which reflects a relatively dry, cold climate that
      coincides with the aeolian loess widely distributed in the northwest China, but
      reverses of the fluvial and marine deposits which experienced a well hydration in
      humid conditions over a long period of time in study area. LPS analysis show that
      grain size from top to bottom of the sections and drill core are homogeneous and
      typical of aeolian sediments. The grain size distribution in the yellow silt is
      characterized by double peaks with main peak of 10-50 MUm and a secondary peak of
      < 5 MUm, similar to that of loess in northwest China but quite different from
      associated fluvial and marine deposits featured by unidirectional change of
      allocation mode of the grain size groups. Based on grain size analysis, DRS
      results, age range of 10-80 ka, and spatial distribution that both of the
      positive landforms and buried topographies in the coastal area of south China
      have this kind of sediments, the yellow silt is considered to represent an
      aeolian deposit formed during the last glacial period, which is called "loess
      like deposits" in our study.

PMID- 25752030
TI  - [Photoelectric parametric test system of LED based on virtual instrument].
AB  - The standardized measuring principle, requirements and implementations of the
      above parameters of LEDs were researched and analyzed in the present paper. Then
      a comprehensive test system involved with optics, machinery and computer was
      designed to accomplish data acquisition, algorithm design and interface design on
      virtual instrument using NI data acquisition card USB6210. And convincing results
      of LEDs' parameters, including peak wavelength, width of half-peak wavelength,
      centroid wavelength, chromaticity coordinates, purity, correlated color
      temperature and the forward voltage/current, were achieved with good consistency
      based on the measured spectrum. The system owns simple interface, reliable
      algorithms and stable results. Respective measurements on five kinds of color of
      LED result in an average error less than 3%, which show an ideal performance of
      the system.

PMID- 25752031
TI  - [Preparation and photoluminescent property of sphere Y2.96Al5O12 0.04Ce3+
      phosphor for white light-emitting diodes].
AB  - Cesium ions doped yttrium aluminum garnet (Y2.96Al5O12 : 0.04Ce3+) phosphors for
      white light emitting diodes (WLED) were successfully prepared by hydrothermal
      thermolysis method. The phase composition, morphology, and photoluminescent
      properties of the prepared powders were investigated by X-ray diffraction,
      scanning electron microscopy, energy-dispersive X-ray spectroscopy, and
      photoluminescence spectroscopy. The results indicated that the successful
      preparation of the pure Y2.96Al5O12 : 0.04Ce3+ powders are spherical particles
      and have good dispersibility. The phosphors were excited by the blue light with
      wavelength of 460 nm, and a broad peak at 550 nm was observed in the emission
      spectrum. Moreover, the emission peak intensity of the YAG : Ce3+ powders
      prepared by hydrothermal-thermolysis method was higher than that of the samples
      prepared by traditional high temperature solid state method. Furthermore, the
      quantum efficiency of the white LED produced by the phosphors and blue chip was
      measured by the integrating sphere coupled fluorescence spectrometer, and the
      results indicated that the absolute quantum efficiency and external quantum
      efficiency of Y2.96Al5O12 : 0.04Ce3+ phosphors prepared by hydrothermal
      thermolysis method were 88.40% and 78.64%, respectively, with the color
      coordinates of (0.453 8, 0.531 8) and the color temperature of 358 4 K. The
      prepared Y2.96Al5O12 : 0.04Ce3+ phosphors exhibited excellent stability and
      repeatability, and acted as excellent yellow phosphors for warm white LED.

PMID- 25752032
TI  - [Fourier transform infrared spectral analysis on peanut (Arachis Hypogaea) plants
      under calcium deficiency stress].
AB  - The objective of the present study was to reveal different tolerance of peanut
      plants to Ca deficiency by determining Ca uptake and Fourier transform infrared
      spectral (FTIR) differences of two peanut cultivars grown in nutrition solution.
      Peanut cultivars LH11 and YZ9102 were selected. Seedlings at the first leaf stage
      were cultivated for 28 days in nutrient solution with 0, 0.01 and 2.0 mmol x L(
      1) Ca treatments, respectively. The results showed that under 0 and 0.01 mmol x
      L(-1) Ca supply, YZ9102 did not show Ca deficiency symptoms and the plant biomass
      did not change, whereas LH11 exhibited shoot-tip necrosis, smaller plant size,
      more lateral branches, and plant dry matter weights decreased significantly.
      YZ9102 had higher plant Ca concentration and Ca accumulation than LH11. Besides,
      for LH11, Ca was mainly accumulated in roots, while for YZ9102 mainly in leaves.
      As compared with plants cultivated in 2.0 mol x L(-1) Ca nutrition, root, stem
      and leaf of LH11 plants under Ca deficiency stress showed higher transmittance at
      peaks 1 060, 1 380, 1 655, 2 922, and 3 420 cm(-1) in FTIR spectra, indicating
      that the contents of protein, sugar and lipid decreased obviously in LH11 plants
      in condition that Ca supply was limited. However, the FTIR spectra of YZ9102 were
      less affected by Ca deficiency. It is suggested that YZ9102 might be more
      tolerant to Ca deficiency.

PMID- 25752033
TI  - [Fast determination of induction period of motor gasoline using Fourier transform
      attenuated total reflection infrared spectroscopy].
AB  - A new method is proposed for the fast determination of the induction period of
      gasoline using Fourier transform attenuated total reflection infrared
      spectroscopy (ATR-FTIR). A dedicated analysis system with the function of
      spectral measurement, data processing, display and storage was designed and
      integrated using a Fourier transform infrared spectrometer module and chemometric
      software. The sample presentation accessory designed which has advantages of
      constant optical path, convenient sample injection and cleaning is composed of a
      nine times reflection attenuated total reflectance (ATR) crystal of zinc selenide
      (ZnSe) coated with a diamond film and a stainless steel lid with sealing device.
      The influence of spectral scanning number and repeated sample loading times on
      the spectral signal-to-noise ratio was studied. The optimum spectral scanning
      number is 15 times and the optimum sample loading number is 4 times. Sixty four
      different gasoline samples were collected from the Beijing-Tianjin area and the
      induction period values were determined as reference data by standard method GB/T
      8018-87. The infrared spectra of these samples were collected in the operating
      condition mentioned above using the dedicated fast analysis system. Spectra were
      pretreated using mean centering and 1st derivative to reduce the influence of
      spectral noise and baseline shift A PLS calibration model for the induction
      period was established by correlating the known induction period values of the
      samples with their spectra. The correlation coefficient (R2), standard error of
      calibration (SEC) and standard error of prediction (SEP) of the model are 0.897,
      68.3 and 91.9 minutes, respectively. The relative deviation of the model for
      gasoline induction period prediction is less than 5%, which meets the
      requirements of repeatability tolerance in GB method. The new method is simple
      and fast. It takes no more than 3 minutes to detect one sample. Therefore, the
      method is feasible for implementing fast determination of gasoline induction
      period, and of a positive meaning in the evaluation of fuel quality.

PMID- 25752034
TI  - [A phase error correction method for the new Fourier transforms spectrometer].
AB  - To decrease the distortion of the recovered spectrum, improve the quantity of the
      recovered spectrum and decrease the influence of the phase error of the new
      spectrum detection system based on MEMS (micro-electro-mechanical systems) micro
      mirrors, a new phase error correction method for this system is proposed in the
      present paper. The source of phase error of the spectrum detection system based
      on MEMS micro-mirrors is analyzed firstly. The analyzed result indicated that the
      phase error of the new spectral Fourier transform detection system is the zero
      drift of the optical path difference, and the phase error can be corrected by
      Zero-crossing sampling which is realized by improving the structure of the
      interferometer system and Mertz product The spectrum detection system is set up
      and the phase error correction method is verified by this system. The experiment
      result is show that the quantity of the recovered spectrum of the spectrum
      detection is improved obviously by using the improved interferometer system and
      Mertz product, and the recovered spectrum has no negative peaks and the side
      lobes is suppressed markedly. This correction method can reduce the influence
      caused by phase error to the system performance well and improve the spectral
      detection performance effectively. In this paper, the origin of the system phase
      error based on the new MEMS micromirror Fourier transform spectroscopy detection
      system is analyzed, and the phase error correction method is proposed. This
      method can improve the performance of the spectrum detection system.

PMID- 25752035
TI  - [Reason analysis of inadaptability and its correction research on the
      authenticity identification model of West Lake Longjing tea based on LVF micro
      NIR spectrometer].
AB  - In the present paper, the micro-NIR spectrometer with the splitter of linear
      variable filter was used to develop the recognition models of the West Lake
      Longjing tea and the ordinary flat tea of the year 2012 and 2013. The NIR
      spectral data of different years and different storage times were decomposed by
      PCA algorithm. The PLS-DA models were developed by the representative samples
      selected by the mathematical characteristics of PCA-scores' distribution in order
      to analyze the reason for the inadaptability of the models according to
      mathematical principles and find out the solution for its correction. Being
      examined by the external validation set, the adaptability of the authenticity
      identification model was enhanced effectively. The result of this research
      indicated that, for the West Lake Longjing tea and the ordinary flat tea, the
      correct recognition rate of the model developed by all different-year samples'
      NIR spectral data would be enhanced effectively. The model developed by the NIR
      spectral data of different storage time samples indicated that the
      physicochemical properties of the ordinary flat tea have changed remarkably after
      cryopreservation for 3 months, while the physicochemical properties of the West
      Lake Longjing tea are relatively stable. The model adaptabilities for different
      years and different storage times were studied according to the mathematical
      perspective of the principal component characteristics of spectral data. After
      the authenticity identification model of West Lake Longjing tea was developed,
      the prediction accuracy was enhanced effectively. This research would provide
      reference for not only the application of NIR spectroscopy in quality grading and
      safety of agricultural products, but also the enhancement of the prediction
      accuracy of the NIR grading models for agricultural products.

PMID- 25752036
TI  - [Changes in chemistry component structure and microstructure characterization of
      acetylated wood before and after UV radiation].
AB  - The poplar powder was acetylated with different duration as sample, processed ray
      radiation by using ultraviolet test box, contrasting the influences to
      lightfastness of wood with different acetylation degree, analyzing changing rules
      of characteristic peaks' intensity which belonged to the chemistry components of
      samples based on FTIR spectra, and the relationship between duration of
      acetylation and changes of chemistry components was established, The results
      showed that: Before UV radiation, the characteristic peaks' intensity of
      acetylated poplar powder at 1 739 cm(-1) which belonged to C = O in saturated
      esters compounds and 1 385 cm(-1) which belonged to C-H in acetate were higher
      than untreated ones', the poplar powder with 40 min's acetylation has the highest
      characteristic peaks' intensity, highest weight gain rate, remarkable acetylation
      effect; After UV radiation, characteristic peaks' intensity of Benzene at 1 504
      cm(-1) which belonged to lignin of poplar powder was obviously higher than
      untreated ones', and characteristic peaks' intensity of poplar powder with 40
      min's acetylation was the highest, this showed that acetylation could effectively
      reduce the light degradation of wood chemistry components, in order to improve
      the lightfastness, especially the poplar powder with 40 min's acetylation; SEM
      photos showed that, the fibrous surface of acetylated poplar powder was more
      smooth and had more narrow particle size than untreated ones', so acetylation can
      effectively improve the stability of wood.

PMID- 25752037
TI  - [Research on wavelength variates selection methods for determination of oil yield
      in oil shales using near-infrared spectroscopy].
AB  - The wavelength selection is an important step in the spectra modeling analysis.
      In the present paper, three wavelength selection methods, including correlation
      coefficient (CC), moving window partial least squares (MWPLS) and uninformative
      variables elimination (UVE), were studied for the determination of oil yield in
      oil shale using near-infrared (NIR) diffuse reflection spectroscopy. The above
      methods were used to eliminate the redundant and irrelevant variables in spectral
      data for enhancing the analytic efficiency and predictive ability of calibration
      model. The effects of thresholds of CC, window width of MWPLS and noise matrix of
      UVE were studied. Partial least squares regression was used to build prediction
      model for predicting oil yield in oil shale, and the performance of PLS models
      constructed with and without the using of wavelength selection methods were
      compared. The results show that any of the three methods can simplify the
      calibration model and improve the performance of model. By using UVE, the total
      number of wavelength variables of spectral data, the RMSECV of calibration model
      and the RMSEP of prediction model were decreased by 22.8%, 9.3% and 4.5%,
      respectively.

PMID- 25752038
TI  - Thermal infrared emissivity spectrum and its characteristics of crude oil slick
      covered seawater.
AB  - Detecting oil slick covered seawater surface using the thermal infrared remote
      sensing technology exists the advantages such as: oil spill detection with
      thermal infrared spectrum can be performed in the nighttime which is superior to
      visible spectrum, the thermal infrared spectrum is superior to detect the
      radiation characteristics of both the oil slick and the seawater compared to the
      mid-wavelength infrared spectrum and which have great potential to detect the oil
      slick thickness. And the emissivity is the ratio of the radiation of an object at
      a given temperature in normal range of the temperature (260-320 K) and the
      blackbody radiation under the same temperature , the emissivity of an object is
      unrelated to the temperature, but only is dependent with the wavelength and
      material properties. Using the seawater taken from Bohai Bay and crude oil taken
      from Gudao oil production plant of Shengli Oilfield in Dongying city of Shandong
      Province, an experiment was designed to study the characteristics and mechanism
      of thermal infrared emissivity spectrum of artificial crude oil slick covered
      seawater surface with its thickness. During the experiment, crude oil was
      continuously dropped into the seawater to generate artificial oil slick with
      different thicknesses. By adding each drop of crude oil, we measured the
      reflectivity of the oil slick in the thermal infrared spectrum with the Fourier
      transform infrared spectrometer (102F) and then calculated its thermal infrared
      emissivity. The results show that the thermal infrared emissivity of oil slick
      changes significantly with its thickness when oil slick is relatively thin (20
      120 MUm), which provides an effective means for detecting the existence of
      offshore thin oil slick In the spectrum ranges from 8 to 10 MUm and from 13. 2 to
      14 MUm, there is a steady emissivity difference between the seawater and thin oil
      slick with thickness of 20 MUm. The emissivity of oil slick changes marginally
      with oil slick thickness and clearly below that of seawater in the spectrum range
      from 11. 7 to 14 MUm, this spectrum range can be practically used to distinguish
      oil slick from seawater; Around the wavelength of 11.72, 12.2, 12.55, 13.48 and
      13.8 MUm, the emissivity of oil slick presents clearly increasing or decreasing
      trends with the increase of its thickness, which are one of the best wavelengths
      for observing the offshore oil slick and estimating its thickness.

PMID- 25752039
TI  - FTIR study of hydrogen bonds in coal under drop weight impact testing.
AB  - There are many hydrogen bonds in coal, which affect the chemical structure and
      properties of coal. FTIR has been applied to the characterization study of the
      hydrogen bonds of Dongpang coals, which were under drop weight impact. There
      exists five kinds of hydrogen bonds in the coal: free OH groups, OH...pi,
      OH...OH, cyclic OH tetramers and OH...N. Absorption strength of intermolecular
      hydrogen bonds markedly declined after impact. Free OH groups mechanical-power
      chemical reacted in drop weight impact testing. The infrared spectrum were curve
      resolved into their component bands. The absorption strength of various hydrogen
      bonds decreased with the increase of impact energy, but the trend was slowing. By
      statistical relationship between then, we find then complying with power function
      relationship. By comparing the exponents of fitted equations, we concluded that
      failure sensitivity sequence of hydrogen bonds to the impact: free OH groups >
      cyclic OH tetramers > OH...N > OH...pi > OH...OH.

PMID- 25752040
TI  - [Identification of Dendrobium varieties by infrared spectroscopy].
AB  - The difference of Dendrobium varieties were analyzed by Fourier transform
      infrared (FTIR) spectroscopy. The infrared spectra of 206 stems from 30
      Dendrobium varieties were obtained, and showed that polysaccharides, especially
      fiber, were the main components in Dendrobium plants. FTIR combined with Wilks'
      Lambda stepwise discriminative analysis was used to identify Dendrobium
      varieties. The effects of spectral range and number of training samples on the
      discrimination results were also analysed. Two hundred eighty seven variables in
      the spectral range of 1 800-1 250 cm(-1) were studied, and showed that the return
      discrimination is 100% correct when the training samples number of each species
      was 2, 3, 4, 5, and 6, respectively, whereas for the remaining samples the
      correct rates of identification were equal to 79.4%, 91.3%, 93.0%, 98.2%, and
      100%, respectively. The same discriminative analyses on five different training
      samples in the spectral range of 1 800-1 500, 1 500-1 250, 1 250-600, 1 250-950
      and 950-650 cm(-1) were compared, which showed that the variables in the range of
      1 800-1 250, 1 800-1 500 and 950-600 cm(-1) were more suitable for variety
      identification, and one can obtain the satisfactory result for discriminative
      analysis when the training sample is more than 3. Our results indicate that FTIR
      combined with stepwise discriminative analysis is an effective way to distinguish
      different Dendrobium varieties.

PMID- 25752041
TI  - [Study on the Tibetan medicine Swertia mussotii Franch and its extracts by
      Fourier transform infrared spectroscopy].
AB  - The objective of the present study is to research the herb of Swertia mussotii
      Franch and its different extracts by tristep infrared spectroscopy. The main
      constitute of Swertia mussotii Franch-gentiamarin, which is also the higher
      content constitute, was selected as the control components to analyze the
      infrared spectroscopy and second derivative infrared spectroscopy of different
      extracts of Swertia mussotii Franch, at the same time, the different
      concentration of ethanol extracts were also analyzed by two-dimensional
      correlation spectroscopy (2D-COS). The results indicated that the intensity of 1
      611 and 1 075 cm(-1) of gentiamarin, which are its two main absorptions in the
      infrared spectra, has the positive correlation with the content change in
      different extracts. The infrared spectroscopy of extracts are similar if the
      polarity of extract solvents is close; with the decreases in solution polarity,
      the intensity of 2 853, 1 733, 1 464, 1 277 and 1 161 cm(-1) in infrared
      spectroscopy of different extracts is increased, the content of esters and the
      extraction percentage terpenoid compounds are also increased; the different
      concentration of ethanol extracts has obviously difference when they are analyzed
      by two-dimensional correlation spectroscopy (2D-COS). The positive correlation
      between the intensity of absorptions and the content of the gentiamarin indicates
      that the infrared spectroscopy can reflect the content change in constitute; the
      similar and the change trend of the different concentrations of ethanol extract
      infrared spectroscopy approve the scientificalness of decoction of traditional
      medicine; infrared spectroscopy that used in the research can be used as an
      accurate, rapid and effective method in the pharmacological activity tests of
      transitional herbal Swertia mussotii F. and it's different extracts, even in the
      research on the tibetan medicine.

PMID- 25752042
TI  - [Measurements of the concentration of atmospheric CO2 based on OP/FTIR method and
      infrared reflecting scanning Fourier transform spectrometry].
AB  - The present paper describes the observations and measurements of the infrared
      absorption spectra of CO2 on the Earth's surface with OP/FTIR method by employing
      a mid-infrared reflecting scanning Fourier transform spectrometry, which are the
      first results produced by the first prototype in China developed by the team of
      authors. This reflecting scanning Fourier transform spectrometry works in the
      spectral range 2 100-3 150 cm(-1) with a spectral resolution of 2 cm(-1). Method
      to measure the atmospheric molecules was described and mathematical proof and
      quantitative algorithms to retrieve molecular concentration were established. The
      related models were performed both by a direct method based on the Beer-Lambert
      Law and by a simulating-fitting method based on HITRAN database and the
      instrument functions. Concentrations of CO2 were retrieved by the two models. The
      results of observation and modeling analyses indicate that the concentrations
      have a distribution of 300-370 ppm, and show tendency that going with the
      variation of the environment they first decrease slowly and then increase rapidly
      during the observation period, and reached low points in the afternoon and during
      the sunset. The concentrations with measuring times retrieved by the direct
      method and by the simulating-fitting method agree with each other very well, with
      the correlation of all the data is up to 99.79%, and the relative error is no
      more than 2.00%. The precision for retrieving is relatively high. The results of
      this paper demonstrate that, in the field of detecting atmospheric compositions,
      OP/FTIR method performed by the Infrared reflecting scanning Fourier transform
      spectrometry is a feasible and effective technical approach, and either the
      direct method or the simulating-fitting method is capable of retrieving
      concentrations with high precision.

PMID- 25752043
TI  - [Feasibility study on an approach for identifying corn kernel varieties with seed
      coating agents via near infrared spectroscopy].
AB  - It is generally accepted that near infrared reflectance spectroscopy (NIRS) can
      be used to identify variety authenticity of bare maize seeds. In practical, maize
      seeds are covered with seed coating agents. Therefore it's of huge significance
      to investigate the feasibility of identifying coated maize seeds by NIRS. This
      study employed NIRS to quickly determine the variety of coated maize seeds.
      Influence of seed coating agent on NIR spectra was discussed. The NIR spectra of
      coated maize seeds were obtained using an innovative method to avoid the impact
      of the seed coating agent. Coated seeds were cut open, and the sections were
      scanned by the spectrometer, so as to acquire the information of the seed itself.
      Then, support vector machine (SVM), soft independent modeling of class analogy
      (SIMCA), and biomimetic pattern recognition (BPR) was employed to establish the
      identification model for four maize varieties, and yield 93%, 95.8%, 98% average
      correct rate respectively. BPR model showed better performance than SVM and SIMCA
      models. The robustness of identification model was tested by seeds harvested from
      four regions and model showed good performance.

PMID- 25752044
TI  - [IR and Raman spectra studies of Rotundine based on DFT].
AB  - Infrared spectroscopy (IR), the normal Raman spectroscopy (NRS) and the surface
      enhanced Raman spectroscopy (SERS) in new Ag/Cu nanomaterial of Rotundine were
      studied in the present paper. The IR and the NRS of Rotundine were calculated by
      the density functional theory (DFT) using B3LYP/6-311+G(d, p), then the spectral
      intensity graph of Rotundine were given. The vibrational peaks were assigned
      comprehensively by the visualization software of Gauss view 5. 0. Rotundine has
      obvious infrared and Raman vibrational peak in the wave number range of 3 300
      2500 and 1 800-600 cm(-1). SnCl2 and PVP was used as capping agent for the silver
      nanoparticles in SERS of Rotundine. Finally, by using the method of cyclic
      immersion well dispersed silver nanoparticles was obtained and achieved good
      enhancement effect. This molecule acquired strong selective enhancement vibration
      peak, In the wave number ranges of 1 500-1 400 and 1 000-700 cm(-1) the
      enhancement effect is most obvious. After analyzed, the methylene of this
      molecule is adsorbed on the silver nanoparticles surface and the angle between
      the benzene ring and the silver substrate is close to 90 degrees. The
      theoretically calculated spectra of Rotundine are consistent with the obtained
      experimental spectra. There are some differences may be due to the interaction
      forces between molecules and so on. The visualization software displayed the
      structure characteristics and molecular group vibration of this molecular
      visually and provided important basis for assigning the vibrational peaks.
      Rotundine is an important traditional Chinese medicine agent contained in many
      kinds of sedative drugs. The study provides a strong basis for the rapid, feature
      and trace identification of Rotundine and also supplies important reference for
      the biological role of central inhibition of analgesic drugs.

PMID- 25752045
TI  - [Infrared, Raman and density functional study of vibration spectra of 2, 3
      dichloropyrazine].
AB  - Fourier transform infrared (FTIR) spectra of 2,3-dichloropyrazine in the region
      400-4000 cm(-1) were measured under solid state condition using KBr pellets
      method and liquid state by the melting method, besides, a Fourier transform Raman
      (FT-Raman) spectra in region 600-4 000 cm(-1) was recorded. Then equilibrium
      geometry of 2,3-DCP was optimized, and based on this, the harmonic vibrational
      frequencies, infrared intensities and Raman activities were calculated using
      B3LYP method of the density function theory (DFT) in conjunction with 6
      311++G(2df, 2pd) basis set, furthermore, a comprehensive anharmonic calculation
      was also been performed for obtaining more accurate vibrational frequencies using
      second-order perturbation theory treatment based on quadratic, cubic and quartic
      force constants. Infrared and Raman spectra were simulated corresponding to
      theory. Experimental FTIR and FT-Raman bands were compared with those positions
      of peaks obtained from anharmonic calculations and intensities or activities from
      harmonic carefully. Each vibrational band was assigned and interpreted in detail
      with help of potential energy distribution (PED) for the first time. In addition,
      it was shown that anharmonic results exactly reproduced to experimental data,
      improved the validity of prediction greatly in vibration frequencies,
      discrepancies between anharmonic and experimental results were limited to below
      10 cm(-1) in most of vibrational bands, even if in the high energy regions, which
      have a poor performance for hanmonic calculation, and these differences would be
      decreased to lower than 19 cm(-1). It is extremely helpful for assigning and
      predicting vibrational spectra. Present conclusion can be expanded to others
      molecular systems.

PMID- 25752046
TI  - [Identification of the characteristic vibrations for 16 PAHs based on Raman
      spectrum].
AB  - In the present paper, by means of density functional theory in B3LYP/6-311++G(d,
      p) method, 16 kinds of pollutants, i. e. polycyclic aromatic hydrocarbons (PAHs):
      naphthalene (Nap), acenaphthylene (AcPy), acenaphthene (Acp), fluorene (Flu),
      phenanthrene (PA), anthracene (Ant), fluoranthene (Fl), pyrene (Pyr), benzo [a]
      anthracene (BaA), fused two naphthalene (CHR), benzo [b] fluoranthene (BbF),
      benzo [k] fluoranthene (BkF), benzo [a] pyrene (BaP), dibenzo (a, h) anthracene
      (DahA), dibenzo [g, h, i] pyrene (BghiP) and indene benzene (1, 2, 3-cd) pyrene
      (IcdP) among the U. S. EPA priority pollutants were selected, whose structures
      were optimized and Raman vibrational frequencies and depolarization were
      calculated. The structure, Raman vibrational frequencies and depolarization were
      basis of identification of PAHs. Studies have shown that Raman vibrations of 16
      PAHs are mainly distributed in three frequency regions: 200-1 000 cm(-1)
      (fingerprint region), 1 000-1 700 cm(-1) and 3 000-3 200 cm(-1) (group frequency
      region), corresponding vibrations were assigned to ring deformation (ring def), C
      C stretching (CCStr), C-H wiggle (CHw) and of these two patterns (CCStrCCw), and
      C-H stretching (CHStr). Further analysis showed that in fingerprint region the
      depolarization of 16 PAHs was reduced with the symmetry of benzene deformation
      vibration enhanced. At the point of minimum depolarization, symmetry and Raman
      peak of benzene ring breathing vibration were found strongest. At the minimum
      differential wave number the strongest peak in fingerprint region was
      distinguishable by micro-Raman spectroscopy. Therefore, 16 PAHs can be
      individually identified by depolarization and the strongest peak in fringerprint
      region. Vibration frequencies and peak intensity distribution of alkanes (Akn),
      olefin (Oe), alkyne (Aye), alcohols and phenols (Aap), aliphatic ether (Ape),
      arylalkyl ether (Aae), aldehydes (Ahd), ketones (Ktn), carboxylic acid (Cba),
      esters (Etr), amines (Aie), nitriles (Nte), amides (Aid), acid anhydride (Ahr),
      aromatic hydrocarbons (Ahc) were not completely consistent with each other, and
      interference can be discharged by the differences of frequency and peak intensity
      distribution.

PMID- 25752047
TI  - Study on the order degree and geochemical characteristics of major elements of
      siliceous rock in eastern Qinling area, China.
AB  - Siliceous rocks were extensively distributed in the marine volcanic sedimentary
      formation of Erlangping Group in the Early Paleozoic in eastern Qinling area.
      These siliceous rocks formed in the same age, but had differences in the degree
      of crystallization and order because of the late diagenetic evolution. In the
      present study, the major elements and order degree of the siliceous rocks were
      studied, which were from the Erlangping Group in Xixia area, Songxian area and
      Nanzhao area of eartern Qinling orogenic belt. As shown in the results, the
      siliceous rocks contained SiO2 with percentage between 84.75% and 94.12% and
      average of 89.09%. The SiO2/(K2O+Na2O) values were from 26.69 to 114.78 with
      65.67 as its average, and the values of SiO2/Al2O3 were from 10.48 to 61.52 with
      average of 30.58. These above characteristics excellently agreed with the
      geochemical characteristics of hydrothermal siliceous rocks, which deposited in
      the continental margin environment. In the Raman analytical results, the quartz
      contributed to the characteristic Raman shifts at 394, 464, 465 and 467 cm(-1).
      In the results of Gaussian fitting the degrees of order increased with the order
      of siliceous rocks of Songxian area, Nanzhao area and Xixia area, which were
      witnessed by the descending in FWHM values of quartz in the siliceous rocks of
      Songxian area, Nanzhao area and Xixia area orderly. Disagreeing with the FWHM
      values of Gaussian fitting, the silica contents of the siliceous rocks had a
      rising trend of Songxian (87.36%), Nanzhao (89.57%), Xixia area (90.35%), which
      meant a descending in impurity elements with the order of Songxian area, Nanzhao
      area and Xixia areas. According to this, there was high agreement between lower
      crystallinity degree and higher purity of silica, and this denoted that the
      rising in order degree of silica would result in lower impurity in siliceous
      rocks. Although the crystallinity degrees could change with the influences of
      temperature, pressure and its natural property, the impurity elements decreased
      with the rising in crystallinity degrees of silica. Although there was excluding
      of impurity elements during the increase in degrees of crystallinity and order,
      the key factor for the diversities of major elements in siliceous rocks was not
      likely to be the excluding of impurity elements during the increase in the
      crystallinity degrees in silica In this study, the Raman analysis exhibited to be
      an effective way to understand the degree of order for the silica of the
      siliceous rocks, which would be a potential way to study the subsequent
      diagenetic evolution of siliceous rocks.

PMID- 25752048
TI  - [Synthesis and characterization of CO-3(2-) doping nano-hydroxyapatite].
AB  - CO3(2-) doping is an effective method to increase the biological activity of nano
      hydroxyapatite (n-HA). In the present study, calcium nitrate and trisodium
      phosphate were chosen as raw materials, with a certain amount of Na2CO3 as a
      source of CO-3(2-) ions, to synthesize nano-carbonate hydroxyapatite (n-CHA)
      slurry by solution precipitation method. The structure and micro-morphology of n
      CHA were characterized by transmission electron microscope (TEM), X-ray
      diffraction (XRD), Fourier transform-infrared spectroscopy (FTIR) and Raman
      spectroscopy (RS). The results revealed that the synthetic n-HA crystals are
      acicular in nanometer scale and have a crystal size of 20-30 nm in diameter and
      60-80 nm in length, which are similar to natural bone apatite. And the
      crystallinity of n-CHA crystals decreases to the increment of CO3(2-). Samples
      with more CO3(2) have composition and structure more similar to the bone apatite.
      The value of lattice parameters a decreases, value of c increases, and c/a value
      increases with the increase in the amount of CO3(2-), in accordance with crystal
      cell parameters change rule of type B replacement. In the AB mixed type
      (substitution OH- and PO4(3-)) CHA, IR characteristic peak of CO3(2-) out-of
      plane bending vibration appears at 872 cm(-1), meanwhile, the asymmetry flexible
      vibration band is split into band at 1 454 cm(-1) and band at 1 420 cm(-1), while
      weak CO3(2)-peak appears at 1 540 cm(-1). CO3(2-) Raman peak of symmetric
      stretching vibration appears at 1 122 cm(-1). CO3(2-) B-type (substitution PO4(3
      )) peak appeared at 1 071 cm(-1). Through the calculation of integral area ratio
      of PO4(3-)/ CO3(2-), OH-/CO3(2-), and PO4(3-)/OH-, low quantity CO3(2-) is B-type
      and high quantity CO3(2-) is A-type (substitution OH-). The results show that the
      synthesized apatite crystals are AB hybrid substitued nano-carbonate
      hydroxyapatite, however B-type replacement is the main substitute mode. Due to
      similarity inthe shape, size, crystal structure and growth mode, the synthesized
      apatite crystals can be called a kind of bone-like apatite.

PMID- 25752049
TI  - [Research on rapid determination of organic matter concentration in aquaculture
      water based on ultraviolet/visible spectroscopy].
AB  - Ultraviolet/visible (UV/Vis) spectroscopy was investigated for the rapid
      determination of chemical oxygen demand (COD) which was an indicator to measure
      the concentration of organic matter in aquaculture water. A total number of 135
      collected turtle breeding water samples were scanned for UV/Vis spectrum,
      uninformative variable elimination (UVE) and successive projections algorithm
      (SPA) were combined as a mixed variable selection method to perform
      characteristic wavelength selection from the full wavelength spectrum, 7
      characteristic wavelengths were selected from full 201 UV/Vis spectral variables,
      which were just 3.48% number of the full range spectrum, and the calibration time
      and complexity of the modeling were greatly reduced. The predicted results which
      were obtained by using least squares-support vector machine (LS-SVM) calibration
      showed that the characteristic wavelengths achieved better results (0.89 for
      correlation coefficient (r), 15.46 mg x L(-1) for root mean square error of
      prediction (RMSEP)) than full wavelengths did (0.88 for r and 15.71 mg x L(-1)
      for RMSEP). The comprehensive results revealed that the UV/Vis characteristic
      wavelengths which were obtained by UVE-SPA variable selection method, combined
      with LS-SVM calibration could apply to the rapid and accurate determination of
      COD in aquaculture water. Moreover, this study laid the foundation for further
      implementation of online analysis of aquaculture water and rapid determination of
      other water quality parameters.

PMID- 25752050
TI  - [Experimental research of turbidity influence on water quality monitoring of COD
      in UV-visible spectroscopy].
AB  - Eliminating turbidity is a direct effect spectroscopy detection of COD key
      technical problems. This stems from the UV-visible spectroscopy detected key
      quality parameters depend on an accurate and effective analysis of water quality
      parameters analytical model, and turbidity is an important parameter that affects
      the modeling. In this paper, we selected formazine turbidity solution and
      standard solution of potassium hydrogen phthalate to study the turbidity affect
      of UV--visible absorption spectroscopy detection of COD, at the characteristics
      wavelength of 245, 300, 360 and 560 nm wavelength point several characteristics
      with the turbidity change in absorbance method of least squares curve fitting,
      thus analyzes the variation of absorbance with turbidity. The results show, In
      the ultraviolet range of 240 to 380 nm, as the turbidity caused by particle
      produces compounds to the organics, it is relatively complicated to test the
      turbidity affections on the water Ultraviolet spectra; in the visible region of
      380 to 780 nm, the turbidity of the spectrum weakens with wavelength increases.
      Based on this, this paper we study the multiplicative scatter correction method
      affected by the turbidity of the water sample spectra calibration test, this
      method can correct water samples spectral affected by turbidity. After treatment,
      by comparing the spectra before, the results showed that the turbidity caused by
      wavelength baseline shift points have been effectively corrected, and features in
      the ultraviolet region has not diminished. Then we make multiplicative scatter
      correction for the three selected UV liquid-visible absorption spectroscopy,
      experimental results shows that on the premise of saving the characteristic of
      the Ultraviolet-Visible absorption spectrum of water samples, which not only
      improve the quality of COD spectroscopy detection SNR, but also for providing an
      efficient data conditioning regimen for establishing an accurate of the chemical
      measurement methods.

PMID- 25752051
TI  - [Ultraviolet-visible spectrometry analysis of insoluble xanthate heavy metal
      complexes].
AB  - A ultraviolet-visible spectrometry method of determining insoluble xanthate heavy
      metal complexes in flotation wastewater was the first time to be put forward. In
      this work, the changes of ultraviolet-visible spectra of xanthate solution after
      the addition of various heavy metal ions were investigated firstly. It was found
      that Pb2+ and Cu2+ can form insoluble complexes with xanthate, while Fe2+, Zn2+
      and Mn2+ have little effect on the ultraviolet absorption of xanthate solution.
      Then the removal efficiencies of filter membrane with different pore sizes were
      compared, and the 0.22 MUm membrane was found to be effective to separate copper
      xanthate or lead xanthate from the filtrate. Furthermore, the results of the
      study on the reaction of sodium sulfide and insoluble xanthate heavy metal
      complexes showed that S(2-) can release the xanthate ion quantitatively from
      insoluble complexes to solution. Based on the above research, it was concluded
      that the amount of insoluble xanthate heavy metal complexes in water samples can
      be obtained through the increase of free xanthate in the filtrate after the
      addition of sodium sulfide. Finally, the feasibility of this method was verified
      by the application to the analysis of flotation wastewater from three ore
      dressing plants in the Thirty-six Coves in Chenzhou.

PMID- 25752052
TI  - [Determination of clopidogrel sulfate in pharmaceutical formulation and
      biological fluids by extraction spectrofluorimetric method].
AB  - A simple and sensitive spectrofluorimetric method has been developed for the
      determination of clopidogrel sulfate in pharmaceutical formulation and human
      urine/serum. It is based on the formation of ion-pair complex between clopidogrel
      sulfate and alizarin red in 0.3 mol x L(-1) hydrochloric acid solution. The ion
      pair complex was extracted in dichloromethane and the fluorescence intensity was
      measured at 550 nm after excitation at 428 nm. The various factors influencing
      ion-pair complex formation and fluorescence determination were discussed. Under
      the optimized conditions, the fluorescence value showed a good linear
      relationship with the clopidogrel sulfate concentration ranging from 1.0 to 11.0
      MUg x mL(-1). The equation of calibration curve was F = 53.32 + 35.01c (MUg x mL(
      1)), r = 0.994, and the detection limit was found to be 0.11 MUg x mL(-1). No
      interference was observed from common co-existing substances or pharmaceutical
      excipient. The determination recoveries of clopidogrel sulfate in pharmaceutical
      formulation and human urine/serum samples were 90.6%-99.3%, 104.6%-109.3%, 96.3%
      105.0%, respectively. The method was successfully applied to detect clopidogrel
      sulfate in clopidogrel sulfate tablet and human urine/ serum. The obtained
      results of clopidogrel sulfate tablet were in good agreement with the results of
      HPLC. Therefore, it is concluded that the proposed method is simple, sensitive
      and rapid for the determination of clopidogrel sulfate in real samples.

PMID- 25752053
TI  - Synthesis and spectroscopic properties of some novel BODIPY dyes.
AB  - BODIPY dyes have some unique properties including high fluorescence quantum
      yield, large extinction coefficiency, narrow absorption and emission band.
      However, most of BODIPY dyes display short emission wavelength and small Stokes
      shift, which limits their applications in biosensing and bioimaging in vivo. For
      bioimaging application, a fluorescent dye with long emission wavelength and large
      Stokes shift is highly desired. To push the absorption and emission spectrum of
      BODIPY to red and even far-red region, a COOEt group was introduced to the meso
      position, and some aromatic group was attached to the 3, 5 position of BODIPY
      core. The structure of resulting compounds were comfirmed by 1H NMR, 13C NMR and
      HR-MS. Dye-1 displays a strong UV-Vis absorption band centered at 536 nm and a
      sharp emission band is located at 592 nm, which is significantly red-shifted (80
      nm) compared to ordinary BODIPY analogs. In addition, the meso-COOEt substituted
      BODIPYs exhibit high quantum yield and red to far-red emission. Notably
      surprisingly, the meso-COOEt substituted BODIPYs display almost separated UV-Vis
      absorption and emission spectra with a large Stokes shift (-60 nm). Time
      dependent density functional theory calculations were conducted to understand the
      structure-optical properties relationship, and it was revealed that the large
      Stokes shift was resulted from the geometric change from the ground state to the
      first excited singlet state. The spectroscopic properties of these BODIPY dyes
      display very subtle solvent-dependence effect. Furthermore, BODIPY was tested for
      its ability of imaging in living cells. The results indicate that Dye-1 is a
      water-soluble and membrane-permeable probe. Therefore, these BODIPYs are a new
      family dyes with excellent spectroscopic properties and can be good candidates
      for bioimaging in living cells.

PMID- 25752054
TI  - [A new multivariate quantitative method of spectral analysis for multicomponent
      system].
AB  - In the spectral analysis, a large-scale application of the traditional
      multivariate analysis methods has been limited by both high cost and poor
      applicability of the calibration models. A new multivariate analysis method was
      proposed for multicomponent systems in the present paper. Determining MTBE
      content in gasoline solution by infrared spectroscopy was studied. The spectra of
      five kinds of gasoline and their 50 narrow distillation fractions were used to
      build the background library. The oblique projection algorithm was applied to the
      spectra of MTBE gasoline solution samples to extract the purespectral signal of
      MTBE in the solution. A unary linear regression curve was built between the pure
      spectral signals of MTBE and their concentrations with a correlation coefficient
      of 0.995 2 and an intercept of 0.025. Compared with the orthogonal projection
      algorithm method and PLS model method, a large amounts of calibration samples and
      complex model are no longer needed by the new method which is simpler, more
      accurate and with better applicability.

PMID- 25752056
TI  - [Pseudo-furocoumarin: synthesis, DNA-binding behavior and cytotoxicity].
AB  - Furocoumarin shows some antitumor activity when it is radiated by the UV light.
      In order to improve the antitumor activity of furocoumarin under standard
      environment conditions, the "minimal DNA-intercalating" hypothesis was firstly
      introduced to the structural modification of furocoumarin, which resulted in the
      design of pseudo-furocoumarin. The pseudo-furocoumarin was synthesized by two
      step reaction including Pechmann reaction catalyzed by conc. H2SO4 and Suzuki
      coupling reaction catalyzed by Pd(PPh3)4. The structural character of the pseudo
      furocoumarin is that the bonding mode of furan ring fused to the coumarin is
      replaced by a chemical single bond between furan ring and coumarin. The
      interaction of the pseudo-furocoumarin with calf thymus DNA (CT-DNA) has been
      respectively investigated by using DNA melting curve, UV-Vis absorption spectra,
      fluorescence spectra and viscosity titration, and the modes of DNA-binding for
      the pseudo-furocoumarin have been proposed. Based on the results of DNA melting
      curve, spectra and viscosity titration, it was suggested that 5a and 5b bind to
      DNA by the partial intercalation and classical intercalation, respectively. The
      DNA-binding behaviors of 5c and 5d have been rarely reported in literature and
      may be interpreted in terms of bridge-structure. All target compounds, except 5b,
      show a decreasing capability of intercalation to DNA. Further, the
      antiproliferative activities of the pseudo-furocoumarin on human lung
      adenocarcinoma (A549), human breast cancer (MCF-7) and human ovarian carcinoma
      cell line (SKOV-3) in vitro were evaluated using the sulforhodamine B (SRB)
      protein statin assay. All pseudo-furocoumarin exhibited an improved anti
      proliferative activity as compared with the control compound psoralen (PS, a
      linear furocoumarin). Interestingly the pseudo-furocoumarin binding to DNA by a
      non-classical intercalation mode showed a stronger anti-proliferative activity
      than PS. The present study extended the applied areas of "minimal DNA
      intercalating" hypothesis, and provided a method for the structural modification
      of furocoumarin as well.

PMID- 25752055
TI  - [Investigation on the cyanine dyes supramolecular assembly and chiral inducement
      by fulvic acid].
AB  - Using cyanine dyes supramolecular as molecular probes to mark FA has important
      significance in life sciences and pharmaceutical chemistry, which can detect FA
      as drug efficacy mechanism and the change in physiological activity. In the
      present paper, we investigated supramolecular assembly and chiral inducement of
      cyanine dyes template by FA with absorption and circular dichroism (CD) spectra.
      The result suggests that FA can induce cyanine dyes from J-aggregation to monomer
      along with different colors change and has strong affinity with cyanine dye
      monomer. The template of FA not only can translate the chirality of MTC H
      aggregation to other two states, but also induce ETC J-aggregation to molecular
      rearrangement and form left-handed helix of J-aggregates. Besides, the
      association of PTC with FA, i. e. binding to FA gave rise to the J-aggregation CD
      signals. Meanwhile, it was inferred that the meso substituent of cyanine dyes
      play an important role in the interaction between FA and the J-aggregation: the
      smaller the meso substituent, the higher the affinity interacted with FA.
      Clearly, the binding abilities between cyanine dyes and FA follow the order of
      MTC>ETC>PTC. These results support that the cyanine dyes supramolecular
      aggregates can be used as a kind of excellent molecular probes for specific
      recognition of FA and achieve the effect of visual inspection.

PMID- 25752057
TI  - [Application of optical flow dynamic texture in land use/cover change detection].
AB  - In the present study, a novel change detection approach for high resolution
      remote sensing images is proposed based on the optical flow dynamic texture
      (OFDT), which could achieve the land use & land cover change information
      automatically with a dynamic description of ground-object changes. This paper
      describes the ground-object gradual change process from the principle using
      optical flow theory, which breaks the ground-object sudden change hypothesis in
      remote sensing change detection methods in the past. As the steps of this method
      are simple, it could be integrated in the systems and software such as Land
      Resource Management and Urban Planning software that needs to find ground-object
      changes. This method takes into account the temporal dimension feature between
      remote sensing images, which provides a richer set of information for remote
      sensing change detection, thereby improving the status that most of the change
      detection methods are mainly dependent on the spatial dimension information. In
      this article, optical flow dynamic texture is the basic reflection of changes,
      and it is used in high resolution remote sensing image support vector machine
      post-classification change detection, combined with spectral information. The
      texture in the temporal dimension which is considered in this article has a
      smaller amount of data than most of the textures in the spatial dimensions. The
      highly automated texture computing has only one parameter to set, which could
      relax the onerous manual evaluation present status. The effectiveness of the
      proposed approach is evaluated with the 2011 and 2012 QuickBird datasets covering
      Duerbert Mongolian Autonomous County of Daqing City, China. Then, the effects of
      different optical flow smooth coefficient and the impact on the description of
      the ground-object changes in the method are deeply analyzed: The experiment
      result is satisfactory, with an 87.29% overall accuracy and an 0.850 7 Kappa
      index, and the method achieves better performance than the post-classification
      change detection methods using spectral information only.

PMID- 25752058
TI  - [Characterization of structural change of ascorbate peroxidase from Chinese kale
      during denaturation by circular dichroism].
AB  - Circular dichroism (CD) is a special absorption spectrum. The secondary structure
      of protein such as alpha-helix, beta-sheet and beta-turn in the far ultraviolet
      region (190-250 nm) has a characteristic CD spectrum. In order to understand the
      activity and structural changes of ascorbate peroxidase from Chinese kale (BaAPX)
      during denaturation, specific activity and percentage of secondary structure of
      BaAPX under different time, temperature and concentration were analyzed by CD
      dynamically. In addition, the percentage of four secondary structures in BaAPX
      was calculated by CD analysis software Dichroweb. The results show that BaAPX is
      a full alpha-type enzyme whose specific activity is positively related to the
      percentage of alpha-helix. During denaturation of BaAPX, three kinds of
      structural changes were proposed: the one-step structural change from initial
      state (N state) to minimum state of alpha-helix (R state) under low concentration
      and low temperature; the one-step structural change from N state to equilibrium
      state (T state) under high concentration and low temperature; the two-step
      structural changes from N state through R state to final T state under heat
      treatment and low temperature renaturation.

PMID- 25752059
TI  - [Spectral quantitative analysis by nonlinear partial least squares based on
      neural network internal model for flue gas of thermal power plant].
AB  - To deal with nonlinear characteristics of spectra data for the thermal power
      plant flue, a nonlinear partial least square (PLS) analysis method with internal
      model based on neural network is adopted in the paper. The latent variables of
      the independent variables and the dependent variables are extracted by PLS
      regression firstly, and then they are used as the inputs and outputs of neural
      network respectively to build the nonlinear internal model by train process. For
      spectra data of flue gases of the thermal power plant, PLS, the nonlinear PLS
      with the internal model of back propagation neural network (BP-NPLS), the non
      linear PLS with the internal model of radial basis function neural network (RBF
      NPLS) and the nonlinear PLS with the internal model of adaptive fuzzy inference
      system (ANFIS-NPLS) are compared. The root mean square error of prediction
      (RMSEP) of sulfur dioxide of BP-NPLS, RBF-NPLS and ANFIS-NPLS are reduced by
      16.96%, 16.60% and 19.55% than that of PLS, respectively. The RMSEP of nitric
      oxide of BP-NPLS, RBF-NPLS and ANFIS-NPLS are reduced by 8.60%, 8.47% and 10.09%
      than that of PLS, respectively. The RMSEP of nitrogen dioxide of BP-NPLS, RBF
      NPLS and ANFIS-NPLS are reduced by 2.11%, 3.91% and 3.97% than that of PLS,
      respectively. Experimental results show that the nonlinear PLS is more suitable
      for the quantitative analysis of glue gas than PLS. Moreover, by using neural
      network function which can realize high approximation of nonlinear
      characteristics, the nonlinear partial least squares method with internal model
      mentioned in this paper have well predictive capabilities and robustness, and
      could deal with the limitations of nonlinear partial least squares method with
      other internal model such as polynomial and spline functions themselves under a
      certain extent. ANFIS-NPLS has the best performance with the internal model of
      adaptive fuzzy inference system having ability to learn more and reduce the
      residuals effectively. Hence, ANFIS-NPLS is an accurate and useful quantitative
      thermal power plant flue gas analysis method.

PMID- 25752060
TI  - [Research on chemical oxygen demand optical detection method based on the
      combination of multi-source spectral characteristics].
AB  - A novel method based on multi-source spectral characteristics of the combination
      is proposed for chemical oxygen demand detection. First, the ultraviolet and near
      infrared spectrum of the actual water samples are collected respectively. After
      pretreatment of the spectrum data, the features of the spectrum are extracted by
      the nonnegative matrix factorization algorithm for training after normalization.
      Particle swarm and least squares support vector machines algorithm are applied to
      predicting chemical oxygen demand of the validation set of water samples. The
      effect of spectrum's base number on the predicted results is discussed. The
      experimental results show that the best base number of the ultraviolet spectrum
      is 5, the best base number of the near infrared spectrum is 2; The validation set
      correlation coefficient of the prediction model is 0.999 8, and the root mean
      square error of prediction is 3.26 mg x L(-1). Experimental results demonstrate
      that the nonnegative matrix factorization algorithm is more suitable for feature
      extraction of spectral data, and the least squares support vector machines
      algorithm as a quantitative model correction method of the actual water samples
      can get good prediction accuracy with different feature extraction methods
      (principal component analysis, independent component analysis), spectroscopic
      methods (ultraviolet spectrum method, near infrared spectrum method) and
      different combination pattern (data direct combination, combining data first,
      then feature extraction) respectively.

PMID- 25752061
TI  - [Vegetation index estimation by chlorophyll content of grassland based on
      spectral analysis].
AB  - Comparing the methods of existing remote sensing research on the estimation of
      chlorophyll content, the present paper confirms that the vegetation index is one
      of the most practical and popular research methods. In recent years, the
      increasingly serious problem of grassland degradation. This paper, firstly,
      analyzes the measured reflectance spectral curve and its first derivative curve
      in the grasslands of Songpan, Sichuan and Gongger, Inner Mongolia, conducts
      correlation analysis between these two spectral curves and chlorophyll content,
      and finds out the regulation between REP (red edge position) and grassland
      chlorophyll content, that is, the higher the chlorophyll content is, the higher
      the REIP (red-edge inflection point) value would be. Then, this paper constructs
      GCI (grassland chlorophyll index) and selects the most suitable band for
      retrieval. Finally, this paper calculates the GCI by the use of satellite
      hyperspectral image, conducts the verification and accuracy analysis of the
      calculation results compared with chlorophyll content data collected from field
      of twice experiments. The result shows that for grassland chlorophyll content,
      GCI has stronger sensitivity than other indices of chlorophyll, and has higher
      estimation accuracy. GCI is the first proposed to estimate the grassland
      chlorophyll content, and has wide application potential for the remote sensing
      retrieval of grassland chlorophyll content. In addition, the grassland
      chlorophyll content estimation method based on remote sensing retrieval in this
      paper provides new research ideas for other vegetation biochemical parameters'
      estimation, vegetation growth status' evaluation and grassland ecological
      environment change's monitoring.

PMID- 25752062
TI  - [Monitoring the thermal plume from coastal nuclear power plant using satellite
      remote sensing data: modeling, and validation].
AB  - Thermal plume from coastal nuclear power plant is a small-scale human activity,
      mornitoring of which requires high-frequency and high-spatial remote sensing
      data. The infrared scanner (IRS), on board of HJ-1B, has an infrared channel IRS4
      with 300 m and 4-days as its spatial and temporal resolution. Remote sensing data
      aquired using IRS4 is an available source for mornitoring thermal plume.
      Retrieval pattern for coastal sea surface temperature (SST) was built to monitor
      the thermal plume from nuclear power plant. The research area is located near
      Guangdong Daya Bay Nuclear Power Station (GNPS), where synchronized validations
      were also implemented. The National Centers for Environmental Prediction (NCEP)
      data was interpolated spatially and temporally. The interpolated data as well as
      surface weather conditions were subsequently employed into radiative transfer
      model for the atmospheric correction of IRS4 thermal image. A look-up-table (LUT)
      was built for the inversion between IRS4 channel radiance and radiometric
      temperature, and a fitted function was also built from the LUT data for the same
      purpose. The SST was finally retrieved based on those preprocessing procedures
      mentioned above. The bulk temperature (BT) of 84 samples distributed near GNPS
      was shipboard collected synchronically using salinity-temperature-deepness (CTD)
      instruments. The discrete sample data was surface interpolated and compared with
      the satellite retrieved SST. Results show that the average BT over the study area
      is 0.47 degrees C higher than the retrieved skin temperature (ST). For areas far
      away from outfall, the ST is higher than BT, with differences less than 1.0
      degrees C. The main driving force for temperature variations in these regions is
      solar radiation. For areas near outfall, on the contrary, the retrieved ST is
      lower than BT, and greater differences between the two (meaning > 1.0 degrees C)
      happen when it gets closer to the outfall. Unlike the former case, the convective
      heat transfer resulting from the thermal plume is the primary reason leading to
      the temperature variations. Temperature rising (TR) distributions obtained from
      remote sensing data and in-situ measurements are consistent, except that the
      interpolated BT shows more level details (> 5 levels) than that of the ST (up to
      4 levels). The areas with higher TR levels (> 2) are larger on BT maps, while for
      lower TR levels (<= 2), the two methods perform with no obvious differences.
      Minimal errors for satellite-derived SST occur regularly around local time 10 a.
      m. This makes the remote sensing results to be substitutes for in-situ
      measurements. Therefore, for operational applications of HJ-1B IRS4, remote
      sensing technique can be a practical approach to monitoring the nuclear plant
      thermal pollution around this time period.

PMID- 25752063
TI  - [Particles size distribution and its influence on remote sensing retrieval of
      turbid Poyang Lake].
AB  - The suspended particle size distribution provides crucial information for the
      study of water environment structure and function. Based on the in-situ data from
      wet and dry season in 2008-2011, the paper studied suspended particle size
      distribution of Poyang Lake and its optical features. The suspended particle size
      distribution showed seasonal variation: the particle size of southern lake was
      larger than that of northern lake in dry season but showed little variation in
      wet season. The suspended particle size distribution exerted influence on
      particulate absorption coefficient, attenuation coefficient and scattering
      coefficient. The particulate absorption coefficient of northern lake was higher
      than that of southern lake. The negative correlation between specific absorption
      coefficient of total suspended particles and median particle size indicated that
      there was "package effect" of mineral particles in turbid Poyang Lake. The
      spatial and temporal distribution of particulate attenuation coefficient and
      scattering coefficient are similar: there were obvious regional differences in
      dry season but few in wet season. There were good correlations among the remote
      sensing reflectance, spectra slope of particle size distribution and spectra
      slope of particulate scattering coefficient. These correlations would provide the
      foundation for remote sensing retrieval of particle size and quantitative
      analysis of influence of suspended particle size on the optical properties. The
      relationship between particle size distribution, particulate back-scattering
      coefficient and bulk refractive index can provide information of particle
      composition in Poyang Lake.

PMID- 25752064
TI  - [Spectral reflectance characteristics of dominant plant species at different eco
      restoring stages in the semi-arid grassland].
AB  - The objective of the research is to apply hyperspectral technique into eco
      restoring monitoring. Through the ASD Fields HH portable field spectrometer, the
      hyperspectral data of dominant plant species in vegetation at different eco
      restoring stages in semi-arid grassland in Helin County, Inner Mongolia were
      collected. The original spectrum reflected data were pretreated by wavelet
      threshold denoising through ViewSpecPro software before analysis. Using the first
      derivative spectra between 660 and 800 nm, and the methods of detrended canonical
      correspondence analysis (DCCA) by Canoco 4. 5 software, the canopy hyperspectral
      datum of 6 dominant plant species was calculated. The results indicated that the
      dominant plant species at early succession stage were Setaria viridis and
      Caragana microphylia, at 5 years eco-restoring stage they were Salsola collina
      and Caragana microphylia and at late succession stage they were Pinus sylvestnis
      var. mongolica and Salsola collina, same as field survey. The graph of DCCA
      indicated that the influential bands of dominant species canopy at early eco
      succession stage were short bands, with a large variation among species, the
      influential bands at 5 years eco-restoring stage were near infrared bands between
      1 000 and 1 050 nm, and that at late stage were near infrared bands of 1 040-1
      075 nm. The DCCA also showed obviously differences in canopy spectrum among 6
      dominant species, and obviously differences among 3 eco-restoring stages.

PMID- 25752065
TI  - [Research on fast classification based on LIBS technology and principle component
      analyses].
AB  - Laser-induced breakdown spectroscopy (LIBS) and the principle component analysis
      (PCA) were combined to study aluminum alloy classification in the present
      article. Classification experiments were done on thirteen different kinds of
      standard samples of aluminum alloy which belong to 4 different types, and the
      results suggested that the LIBS-PCA method can be used to aluminum alloy fast
      classification. PCA was used to analyze the spectrum data from LIBS experiments,
      three principle components were figured out that contribute the most, the
      principle component scores of the spectrums were calculated, and the scores of
      the spectrums data in three-dimensional coordinates were plotted. It was found
      that the spectrum sample points show clear convergence phenomenon according to
      the type of aluminum alloy they belong to. This result ensured the three
      principle components and the preliminary aluminum alloy type zoning. In order to
      verify its accuracy, 20 different aluminum alloy samples were used to do the same
      experiments to verify the aluminum alloy type zoning. The experimental result
      showed that the spectrum sample points all located in their corresponding area of
      the aluminum alloy type, and this proved the correctness of the earlier aluminum
      alloy standard sample type zoning method. Based on this, the identification of
      unknown type of aluminum alloy can be done. All the experimental results showed
      that the accuracy of principle component analyses method based on laser-induced
      breakdown spectroscopy is more than 97.14%, and it can classify the different
      type effectively. Compared to commonly used chemical methods, laser-induced
      breakdown spectroscopy can do the detection of the sample in situ and fast with
      little sample preparation, therefore, using the method of the combination of LIBS
      and PCA in the areas such as quality testing and on-line industrial controlling
      can save a lot of time and cost, and improve the efficiency of detection greatly.

PMID- 25752066
TI  - [A multivariate nonlinear model for quantitative analysis in laser-induced
      breakdown spectroscopy].
AB  - Most quantitative models used in laser-induced breakdown spectroscopy (LIBS) are
      based on the hypothesis that laser-induced plasma approaches the state of local
      thermal equilibrium (LTE). However, the local equilibrium is possible only at a
      specific time segment during the evolution. As the populations of each energy
      level does not follow Boltzmann distribution in non-LTE condition, those
      quantitative models using single spectral line would be inaccurate. A
      multivariate nonlinear model, in which the LTE is not required, was proposed in
      this article to reduce the signal fluctuation and improve the accuracy of
      quantitative analysis. This multivariate nonlinear model was compared with the
      internal calibration model which is based on the LTE condition. The content of Mn
      in steel samples was determined by using the two models, respectively. A minor
      error and a minor relative standard deviation (RSD) were observed in multivariate
      nonlinear model. This result demonstrates that multivariate nonlinear model can
      improve measurement accuracy and repeatability.

PMID- 25752067
TI  - [Comparative investigation of underwater-LIBS using 532 and 1 064 nm lasers].
AB  - With the hope of applying laser induced breakdown spectroscopy (LIBS) to the
      ocean applications, the laser energy at 532 and 1 064 nm wavelength with 3 and 40
      mj respectively was used, which was near their breakdown threshold. Extensive
      experimental investigations of LIBS from CaCl2 water solution were carried out in
      this paper using different laser wavelengths of 532 and 1 064 nm. The obtained
      results show that compared with the 532 nm laser, the 1 064 nm laser can induce
      the plasma in water with higher emission intensity and longer lifetime, while the
      reproducibility of LIBS signal under 1 064 nm laser is poorer. On the other hand,
      due to the different attenuation ratios of 532 and 1 064 nm laser energies in
      water, the LIBS signal of 1 064 nm laser decreases a lot within the transmission
      distance range 2-5 cm, while LIBS signal of 532 nm remains the same, because that
      the wavelength of 532 nm lies in the "transmission window" of the water solution.
      This study will provide valuable design considerations for the development of
      LIBS-sea system in near future.

PMID- 25752068
TI  - [Determination of metal elements in PM2. 5 by ICP-OES with microwave digestion].
AB  - In the present work, a method was developed for determining lead, zinc, copper,
      cadmium, znd chromium in PM2. 5 by inductively coupled plasma-optical emission
      spectrometry (ICP-OES) analysis with microwave digestion and glass fibre filter
      collection of samples. The microwave digestion systems were investigated and the
      experimental conditions were optimized. The results show that (1) HNO3-H2O02
      digestion system is more stable and complete than HNO3-HCl and HNO3-H2 SO4
      digestion systems; (2) The most sensitive emission wave length of lead, zinc,
      copper, cadmium, and chromium are 220.353, 213.857, 327.393, 228.802, and 267.716
      nm, respectively; (3) The highest signal-to-noise ratios were observed under the
      conditions: RF power of 1 300 W, peristaltic pump flow rate of 1.5 mL x min(-1),
      cooling gas flow rate of 15 L x min(-1), and carrier gas flow rate of 0.8 L x
      min(-1). In addition, the detection limit for these elements ranged between 2.02
      x 10(-3) and 8.20 x 10(-3(MUg x mL(-1), the relative standard deviations (RSD, n
      = 6) for the samples were in the range of 1.86%-2.82%, and the recovery for the
      elements determined was from 91.6% to 103.7%. The proposed method was used for
      determination of the above five elements in atmospheric fine particulate matter
      at Wanzhou Monitoring Site of Chongqing Institute of Green and Intelligent
      Technology. The results revealed that the atmospheric fine particulate matter at
      this monitoring site was not polluted by cadmium and chromium, lead was at the
      level of potential contamination, while zinc and copper were at the level of
      slight pollution.

PMID- 25752069
TI  - [Comparison of soil heavy metals determined by AAS/AFS and portable X-ray
      fluorescence analysis].
AB  - Total concentrations of Cu, Pb, As, Cr, Ni and Zn were determined for 53 soil
      samples using portable X-ray fluorescence (PXRF) system in in-situ and ex-situ
      (Lab.) conditions. PXRF metal concentrations were statistically compared with
      analytical results from traditional AAS/AFS analysis. The ability of PXRF
      instrument to produce comparable analytical results to the reference method was
      assessed by linear regression. To investgate the effects of soil moisture on
      PXRF, the in-situ moisture content of all soil samples was quantified and the
      metal concentrations of selected samples with known moisture contents were
      measured too. The results showed that the detection limits of PXRF for Cu, Pb,
      As, Cr, Ni and Zn were 10.6, 8.1, 5.7, 22.5, 21.6 and 10.4 mg kg(-1)
      respectively. A good degree of linearity was found for Pb, Cr, Ni and Zn in in
      situ condition. While in ex-situ condition, quantitative level data were achieved
      across the entire range of samples tested for Cu, Pb, Cr, Ni and Zn. X-ray
      fluorescence spectrometry was shown to be an effective tool for quantification
      and rapid assessment of heavy metals in soils. Soil moisture content did affected
      the performance of PXRF, the mean percent difference for soil samples in-situ
      with moisture content less than 15% and higher than 25% was -17% and -31%
      respectively. In ex-situ condition, as the soil moisture content increased from
      air dried level to 30%, the mean percent difference decreased from 10% to -24%.
      The dilution effect of moisture in soils may cause discrepancies with
      conventional analytical results and induce worse data quality, and it should be
      controlled within 0-25% in in-situ condition.

PMID- 25752070
TI  - [X-ray powder diffraction of clay minerals of SZK01 core of Zabuye Lake, Tibetan
      Plateau].
AB  - The present article chooses the core from the borehole SZK01 in Zabuye Lake as
      the main research object. According to the results of X-ray powder diffraction of
      clay minerals, the major components are illite, illite and smectite mixed layer
      mineral (I/S), kaolinite and chlorite. According to the different species and
      contents of clay, integration of the characteristics of mineral and the results
      of Delta18O, we reestablished the evolution process of paleoclimate in Zabuye
      Lake. In compaison with SZK02 core in Zabuye, Greenland GISP2 and GRIP and Guliya
      ice core, it contains 5 stages since 115 ka in Zabuye: the last interglacial (15
      75.5 ka), the earlier last glacial (75.5-60 ka), the interstage of the last
      glacial (60-30.1 ka), the last glacial maximum (30.1-16.7 ka) and deglacial
      holocene (since 16.7 ka). We also recognized 6 Heinrich events (H1-H6) and warm
      event in 71 ka. In particular, the content of kaolinite is low, with the negative
      skewed value of Delta18O in 52-53 ka, while the value of Delta18O in SZK02 and
      Guliya ice core is negative-skewed too, indicating the cold event in Tibet
      plateau, named H5-1. All the above demonstrated that the climate in Tibet plateau
      is global since the earlier last glacial, and it also has regional
      characteristics.

PMID- 25752071
TI  - [New methodology for heavy metals measurement in water samples by PGNAA-XRF].
AB  - In the present paper, a new combined detection method was proposed using prompt
      gamma neutron activation analysis (PGNAA) and characteristic X-ray fluorescence
      to improve the heavy metals measurement accuracy for in-situ environmental water
      rejects analysis by PGNAA technology. Especially, the characteristic X-ray
      fluorescence (XRF) of heavy metals is induced by prompt gamma-ray directly
      instead of the traditional excitation sources. Thus, a combined measurement
      facility with an 241 AmBe neutron source, a BGO detector and a NaI-Be detector
      was developed to analyze the pollutants in water. The two detectors were
      respectively used to record prompt gamma-ray and characteristic X-ray
      fluorescence of heavy metals. The prompt gamma-ray intensity (I(gamma)) and
      characteristic X-ray fluorescence intensity (I(x)) was determined by MCNP
      calculations for different concentration (c(i)) of chromium (Cr), cadmium (Cd),
      mercury (Hg) and lead (Pb), respectively. The simulation results showed that
      there was a good linear relationship between I(gamma), I(x) and (c(i)),
      respectively. The empirical formula of combined detection method was given based
      on the above calculations. It was found that the combined detection method was
      more sensitive for high atomic number heavy metals like Hg and Pb measurement
      than low atomic number like Cr and Cd by comparing and analyzing I(gamma) and
      I(x). The limits of detection for Hg and Pb by the combined measurement
      instrument were 17.4 and 24.2 mg x kg(-1), respectively.

PMID- 25752072
TI  - [Atmospheric parameter estimation for LAMOST/GUOSHOUJING spectra].
AB  - It is a key task to estimate the atmospheric parameters from the observed stellar
      spectra in exploring the nature of stars and universe. With our Large Sky Area
      Multi-Object Fiber Spectroscopy Telescope (LAMOST) which begun its formal Sky
      Survey in September 2012, we are obtaining a mass of stellar spectra in an
      unprecedented speed. It has brought a new opportunity and a challenge for the
      research of galaxies. Due to the complexity of the observing system, the noise in
      the spectrum is relatively large. At the same time, the preprocessing procedures
      of spectrum are also not ideal, such as the wavelength calibration and the flow
      calibration. Therefore, there is a slight distortion of the spectrum. They result
      in the high difficulty of estimating the atmospheric parameters for the measured
      stellar spectra. It is one of the important issues to estimate the atmospheric
      parameters for the massive stellar spectra of LAMOST. The key of this study is
      how to eliminate noise and improve the accuracy and robustness of estimating the
      atmospheric parameters for the measured stellar spectra. We propose a regression
      model for estimating the atmospheric parameters of LAMOST stellar(SVM(lasso)).
      The basic idea of this model is: First, we use the Haar wavelet to filter
      spectrum, suppress the adverse effects of the spectral noise and retain the most
      discrimination information of spectrum. Secondly, We use the lasso algorithm for
      feature selection and extract the features of strongly correlating with the
      atmospheric parameters. Finally, the features are input to the support vector
      regression model for estimating the parameters. Because the model has better
      tolerance to the slight distortion and the noise of the spectrum, the accuracy of
      the measurement is improved. To evaluate the feasibility of the above scheme, we
      conduct experiments extensively on the 33 963 pilot surveys spectrums by LAMOST.
      The accuracy of three atmospheric parameters is log Teff: 0.006 8 dex, log g:
      0.155 1 dex, [Fe/H]: 0.104 0 dex.

PMID- 25752073
TI  - [The backgroud sky subtraction around [OIII] line in LAMOST QSO spectra].
AB  - At present, most sky-subtraction methods focus on the full spectrum, not the
      particular location, especially for the backgroud sky around [OIII] line which is
      very important to low redshift quasars. A new method to precisely subtract sky
      lines in local region is proposed in the present paper, which sloves the problem
      that the width of Hbeta-[OIII] line is effected by the backgroud sky subtraction.
      The exprimental results show that, for different redshift quasars, the spectral
      quality has been significantly improved using our method relative to the original
      batch program by LAMOST. It provides a complementary solution for the small part
      of LAMOST spectra which are not well handled by LAMOST 2D pipeline. Meanwhile,
      This method has been used in searching for candidates of double-peaked Active
      Galactic Nuclei.

PMID- 25752074
TI  - [A novel spatial modulation Fourier transform spectrometer with adjustable
      spectral resolution].
AB  - In the premise of fulfilling the application requirement, the adjustment of
      spectral resolution can improve efficiency of data acquisition, data processing
      and data saving. So, by adjusting the spectral resolution, the performance of
      spectrometer can be improved, and its application range can be extended. To avoid
      the problems of the fixed spectral resolution of classical Fourier transform
      spectrometer, a novel type of spatial modulation Fourier transform spectrometer
      with adjustable spectral resolution is proposed in this paper. The principle of
      the novel spectrometer and its interferometer is described. The general
      expressions of the optical path difference and the lateral shear are induced by a
      ray tracing procedure. The equivalent model of the novel interferometer is
      analyzed. Meanwhile, the principle of the adjustment of spectral resolution is
      analyzed. The result shows that the novel spectrometer has the merits of
      adjustable spectral resolution, high stability, easy assemblage and adjustment
      etc. This theoretical study will provide the theoretical basis for the design of
      the spectrometer with adjustable spectral resolution and expand the application
      range of Fourier transform spectrometer.

PMID- 25752075
TI  - [Analysis of optic crosstalk correction for pushbroom hyperspectral data].
AB  - Based on the imaging process of pushbroom hyperspectral imager, a correction
      method for optic crosstalk was developed. An area that has white calibration
      target was selected as reference data. The target pixels crosstalk quantity was
      gained using the subtraction between the two lines of reference data, and it was
      fitted to restrain noise. Using recursion method, crosstalk quantity of single
      pixel was calculated from the fitted function, and it could be used to correct
      the optical crosstalk of the whole data. Three PHI (pushbroom hyperspectral
      imager) data which have different ground scene were corrected. It was showed that
      optical crosstalk in corrected data is lightened obviously, and the data quality
      is improved effectively in both the spectral dimension and spatial dimension. The
      spectral changing caused by optical crosstalk is also corrected, and the bands
      with definition increased more than 50% accounts for 83% of the total bands.
      Optic crosstalk is obtained form hyperspectral data itself which is independent
      of other data source. It is proved that the correction method is valid, and it is
      applicable for different ground type. The correction method also provides a way
      to measure the optic crosstalk of hyperspectral imager in the lab.

PMID- 25752076
TI  - [High-speed target recognition positioning system based on multi-spectral
      radiation characteristics].
AB  - In order to achieve quick recognition and positioning of the high-speed target,
      using multi-spectral radiation combined with acoustic positioning technology, in
      the passive state, the blast wave spectral characteristics and acoustic
      characteristics of the measured target were rapidly obtained, thus analysis was
      performed to determine the type, location and other important parameters. Multi
      spectral radiation detection target recognition formula was deduced. The accuracy
      of the optical path length and the logical integration time was calculated by
      shock acoustic positioning method. Experiments used 5.56 mm NATO bullets, 7.62 mm
      56-rifle bullets, 12.7 mm 54 type machine-gun bullets as a target identified
      projectile. Interference fringes were collected by the static Fourier transform
      interferometer system and ICX387AL type CCD, and the peak of sound pressure was
      collected using 2209 pulse sound pressure meter made by B & K Company from
      Denmark Experimental results show that for the 5.56 mm NATO bullets, the three
      characteristic wavelengths position amplitudes are close to each other, with the
      maximum amplitude at 966 nm; For the 7.62 mm 56-rifle bullets, 935 nm is the
      maximum amplitude position, while for 966 and 997 nm position the magnitudes are
      sunukar; For 12.7 mm 54 type machine-gun bullets, the three wavelengths show a
      ladder-like distribution. With the increase in the detection distance spectral
      radiation energy decreased. Meanwhile, with the decrease in the total radiation
      spectrum, the spectrum of target was affected strongly by background noise, and
      the SNR of system was decreased. But the spectral characteristics of different
      target still exist, the target species can be identified by the system with the
      ratio algorithm of characteristic peaks. Through spectral calibration and
      characteristic wavelengths extraction, the target can successfully identify the
      type of projectile and target position, and it meets the design requirements.

PMID- 25752077
TI  - [Study of spectrum characteristic of humidity sensor based on series coupled two
      micro-ring resonators].
AB  - A novel humidity sensor of polyimide (PI) based on the series coupled two-micro
      ring resonators is proposed in the present paper. The transfer function of the
      micro ring resonator was calculated by using the transfer matrix method and the
      coupled mode theory. The authors compared the output spectrum characteristics of
      the traditional single micro-ring and series coupled two-micro-ring with
      different radii. The refractive index of the PI waveguide changes with different
      environmental humidity and this will lead to the drift of the output spectrum of
      the micro-ring resonator. By detecting the drift of the output spectrum we can
      measure the humidity, and the sensitivity and the sensing-range of the sensor are
      acquired accordingly. We also analyzed the output spectrum characteristics of
      resonators at different humidity sensing part. The theoretical results show the
      good performance of humidity sensor which could be used as the optimum sensing
      unit when the whole structure of the series coupled two-micro-ring resonators
      serves as the sensing part. The sensing-range and sensitivity of the system are
      improved by series micro-ring resonators of different radii compared to the
      conventional sensor with single micro-ring resonator. The free spectral range
      (FSR) of resonator reaches to 0.15 MUm, the sensing-range is 10% RH-80% RH, and
      the sensitivity is 0.001 7 MUm (% RH)(-1). Series coupled two-micro-ring with
      different radii gives theoretical instruction for producing integrated humidity
      sensor with low-cost, simple structure and high sensitivity.

PMID- 25752078
TI  - [Effect evaluation of optical magnification errors for coded aperture
      spectrometer].
AB  - In the present paper, we simulated the system optical magnification error's
      influence on the quality of reconstructed image, analyzed the variant of the
      coded aperture with different optical magnification, then proposed an accurate
      curve of image quality and optical magnification in 128 x 128 code template,
      which provide important references for the design and development of push-broom
      coded aperture spectrometer.

PMID- 25752079
TI  - [Characteristics of phosphorus fractions in sediments of constructed wetlands].
AB  - In order to better understand phosphorus (P) cycle in wetland ecosystem, the
      characteristics of phosphorus fractions in sediments of Heituwa constructed
      wetland system were investigated using soil organic phosphorus (Po) fractionation
      scheme and 31P-NMR technology. The concentrations of TP, Pi, Po and soil organic
      matter were all increased along the flow direction. Four kinds of P-compounds
      (orthophosphate, orthophosphate monoesters, orthophosphate diesters, and
      pyrophosphate) were detected in the NMR spectrum. Orthophosphate and phosphate
      monoester accounted for the dominants position in sediment phosphorus. This study
      indicates that the Po in sediment plays an importance role in wetland ecosystem
      and suggested that more attention should be paid to Po, especially to DNA-P and
      pyrophosphate in further research and management of constructed wetlands.
      Compared with the traditional chemical analysis method, 31P-NMR method has sample
      preparation relatively simple and is less destructive, with components analyzed
      completely. Using 31P-NMR technology, the cognition of wetland phosphorus cycle,
      especially organophosphate, will be expected to get new breakthrough.

PMID- 25752080
TI  - [Sample preparation methods for chromatographic analysis of organic components in
      atmospheric particulate matter].
AB  - The determination of organic composition in atmospheric particulate matter (PM)
      is of great importance in understanding how PM affects human health, environment,
      climate, and ecosystem. Organic components are also the scientific basis for
      emission source tracking, PM regulation and risk management. Therefore, the
      molecular characterization of the organic fraction of PM has become one of the
      priority research issues in the field of environmental analysis. Due to the
      extreme complexity of PM samples, chromatographic methods have been the chief
      selection. The common procedure for the analysis of organic components in PM
      includes several steps: sample collection on the fiber filters, sample
      preparation (transform the sample into a form suitable for chromatographic
      analysis), analysis by chromatographic methods. Among these steps, the sample
      preparation methods will largely determine the throughput and the data quality.
      Solvent extraction methods followed by sample pretreatment (e. g. pre-separation,
      derivatization, pre-concentration) have long been used for PM sample analysis,
      and thermal desorption methods have also mainly focused on the non-polar organic
      component analysis in PM. In this paper, the sample preparation methods prior to
      chromatographic analysis of organic components in PM are reviewed
      comprehensively, and the corresponding merits and limitations of each method are
      also briefly discussed.

PMID- 25752081
TI  - [Dispersive liquid-liquid microextraction based on solidification of floating
      organic droplets combined with high performance liquid chromatography-tandem mass
      spectrometry for determination of benzotriazole ultraviolet stabilizers in
      seawater].
AB  - A novel dispersive liquid-liquid microextraction method based on solidification
      of floating organic droplets (DLLME-SFO) technique was developed for the
      determination of seven benzotriazole ultraviolet (UV) stabilizers in seawater
      samples by high performance liquid chromatography with tandem mass spectrometry.
      The optimal liquid-liquid microextraction experiment conditions were as follows:
      20 MUL of 1-dodecanol as extraction solvent, 400 MUL of methanol as dispersive
      solvent, 8% (mass percentage) NaCl, pH of the sample below 6, vortex oscillation
      extraction time in 2 min. The separation of target compounds was achieved by
      combining a Hypersil GOLD analytical column (150 mm x 2.1 mm, 5 MUm) with
      methanol-water as mobile phase with gradient elution program. Quantitative
      determination by ESI-MS/MS was achieved using positive ion mode with multiple
      reaction monitoring mode. The proposed method showed good linearity with the
      correlation coefficients all above 0. 99. The blank samples were spiked at three
      levels and the average recoveries of target compounds ranged from 68.3% to 127.5%
      with the RSDs from 0.9% to 15.2%. The limits of detection (LODs) and limits of
      quantification (LOQs) of the method for the seven target compounds were in the
      ranges of 0.001-0.090 MUg/L and 0.003-0.300 MUg/L, respectively. The developed
      method was successfully applied for the analysis of the UV stabilizers in
      seawater at Dalian seashores, and some of the benzotriazoles were detected. The
      method is simple, rapid, environment friendly, highly sensitive and suitable for
      rapid analysis of benzotriazole UV stabilizers in seawater.

PMID- 25752082
TI  - [Simultaneous analysis of 14 short- and long-chain perfluorinated compounds in
      water by liquid chromatography-tandem mass spectrometry using solid phase
      extraction].
AB  - A solid phase extraction (SPE)-ultrahigh pressure liquid chromatography (UPLC)
      method coupled with tandem mass spectrometry was developed for the simultaneous
      analysis of the 14 short- and long-chain perfluorinated compounds (PFCs) in
      water. Water sample was concentrated and purified through WAX mixed-mode SPE
      cartridges. The separation of PFCs was performed on a BEH C18 column with
      gradient elution using methanol-5 mmol/L ammonium acetate as mobile phases. The
      PFCs were quantified by internal standard method in multiple-reaction monitoring
      mode. The calibration curves of the 14 PFCs were linear in the range of 0.1-50
      MUg/L with the correlation coefficients > 0.99. The limits of detection (S/N = 3)
      and quantitation (S/N = 10) of the method were 0.09-1.15 ng/L and 0.29-3.85 ng/L,
      respectively. The average recoveries of eight PFCs at three spiked levels of 2,
      10 and 20 ng/L were 85.0%, 120.2% and 117.4%, with the relative standard
      deviations of 9.2%, 9.0% and 6.6%, respectively. The recoveries of the rest six
      PFCs were low due to unavoidable strong adsorption on the bottle/tube walls
      during sample pretreatment. The method was applied in the determination of PFCs
      in real samples of a lake in South China. Four short-chain and five long-chain
      PFCs were detected with mass concentrations of 41.29-49.05 ng/L and 98.43-111.02
      ng/L, respectively. The results show that the method is suitable for the
      simultaneous analysis of short- and long-chain perfluorinated compounds in
      environmental water.

PMID- 25752083
TI  - [Optimization of sample pretreatment method for the determination of typical
      artificial sweeteners in soil by high performance liquid chromatography-tandem
      mass spectrometry].
AB  - The sample pretreatment method for the determination of four typical artificial
      sweeteners (ASs) including sucralose, saccharin, cyclamate, and acesulfame in
      soil by high performance liquid chromatography-tandem mass spectrometry (HPLC
      MS/MS) was optimized. Different conditions of extraction, including four
      extractants (methanol, acetonitrile, acetone, deionized water), three kinds of
      ionic strength of sodium acetate solution (0.001, 0.01, 0.1 mol/L), four pH
      values (3, 4, 5 and 6) of 0.01 mol/L acetate-sodium acetate solution, four set
      durations of extraction (20, 40, 60, 120 min) and number of extraction times (1,
      2, 3, 4 times) were compared. The optimal sample pretreatment method was finally
      set up. The sam- ples were extracted twice with 25 mL 0.01 mol/L sodium acetate
      solution (pH 4) for 20 min per cycle. The extracts were combined and then
      purified and concentrated by CNW Poly-Sery PWAX cartridges with methanol
      containing 1 mmol/L tris (hydroxymethyl) amino methane (Tris) and 5% (v/v)
      ammonia hydroxide as eluent. The analytes were determined by HPLC-MS/MS. The
      recoveries were obtained by spiked soil with the four artificial sweeteners at 1,
      10, 100 MUg/kg (dry weight), separately. The average recoveries of the analytes
      ranged from 86.5% to 105%. The intra-day and inter-day precisions expressed as
      relative standard deviations (RSDs) were in the range of 2.56%-5.94% and 3.99%
      6.53%, respectively. Good linearities (r2 > 0.995) were observed between 1-100
      MUg/kg (dry weight) for all the compounds. The limits of detection were 0.01-0.21
      kg/kg and the limits of quantification were 0.03-0.70 MUg/kg for the analytes.
      The four artificial sweeteners were determined in soil samples from farmland
      contaminated by wastewater in Tianjin. This method is rapid, reliable, and
      suitable for the investigation of artificial sweeteners in soil.

PMID- 25752084
TI  - [Determination of hexavalent chromium in atmospheric particles PM2.5 and PM10 by
      ion chromatography with inductively coupled plasma mass spectrometry].
AB  - An analytical method using ion chromatography with inductively coupled plasma
      mass spectrometry (IC-ICP-MS) for the determination of hexavalent chromium
      (Cr(VI)) in atmospheric particles PM2.5 and PM10 was established. The Cr(VI) in
      the atmospheric particles was extracted ultrasonically with sodium bicarbonate
      solution. An anion exchange column (AG7, 50 mm x 4 mm) with 75 mmol/L ammonium
      nitrate solution (containing 0.22 g/L Na2EDTA, pH 7.0) as mobile phase was used
      for the separation. ICP-MS was used as a detector for the determination of
      hexavalent chromium. The calibration curve was linear in the range of 0.05-5
      MUg/L and the correlation coefficient was 0.999 9 for Cr(VI). The cellulose
      filter was fit for sampling. With the alkaline cellulose filter, the recovery of
      Cr(VI) increased from 75% to 102%. The recovery was complete and stable when the
      samples were sonicated in 20 mmol/L sodium bicarbonate solution for 30 min. The
      limit of quantification (LOQ) of Cr(VI) was 0.000 4 ng/m3 when the sampling
      volume was 20 m3. The average recoveries of Cr(VI) in the spiked PM2.5 and PM10
      samples ranged from 91.6% to 102% with the relative standard deviations not more
      than 7.6%. The method is efficient and reliable. It can meet the requirement for
      the determination of Cr(VI) in atmospheric particles.

PMID- 25752085
TI  - [Analysis of perfluorooctanoic acid by high performance liquid chromatography
      with 3,4-dichloroaniline derivatization].
AB  - A simple derivatization method followed by high performance liquid chromatography
      (HPLC) for the analysis of perfluorooctanoic acid (PFOA) was developed. PFOA was
      firstly derivatized with 3,4-dichloroaniline (DCA) using carbodiimide method. The
      typical amidate product was characterized by mass spectrometry (MS). It can be
      detected by a UV detector at maximum absorption wavelength of 255 nm. It was
      isolated well by methanol/H2O (8/2, v/v) as mobile phase. The DCA derivatization
      of PFOA in organic or aqueous solutions was opti- mized. The following
      purification procedures with thin layer chromatography (TLC) and HPLC separations
      were established. Using external standard method with the authentic PFOA-DCA
      derivative as standard, the limit of instrumental quantification was found to be
      0. 5 mg/L. Good linear correlation coefficients were observed in 0.5-50.0 mg/L.
      The accuracy of the method was evaluated by the recovery measurements on spiked
      samples. The recoveries for the spiked samples (1.0 mg/L) in organic phase and
      aqueous phase were 91.8%-108.7% and 42.1%-53.7%, respectively. Comparing to the
      reported pre-column derivatization methods followed by HPLC for the determination
      of PFOA, this method has the advantages of mild reaction conditions, very stable
      derivative, easy operation, low cost, etc. The method was successfully applied
      for the quantification of PFOA in photodegradation experiments, and the results
      were consistent with those determined by LC/MS. Considering the combination of
      the preconcentration step, it has a potential for the application of the analysis
      of samples containing relatively low concentrations, such as MUg/L levels of PFOA
      obtained from environmental or scientific experiments.

PMID- 25752086
TI  - [Pollution characteristics of polychlorinated dibenzo-p-dioxins, polychlorinated
      dibenzofurans and polychlorinated biphenyls in PM2.5 of Hangzhou City during
      winter].
AB  - In order to evaluate the distributions and concentrations of polychlorinated
      dibenzo-p-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs) and
      polychlorinated biphenyls (PCBs) in aerosol, PM2.5 samples were collected
      concurrently at five sites in January 2014 in Hangzhou. The analytes were
      analyzed with isotope dilution and high resolution gas chromatography/high
      resolution mass spectrometry (HRGC/HRMS) based on US EPA 1613B method and US EPA
      1668B method. The results showed that the mass concentrations of PM2.5 were in
      the range of 85-168 MUg/m3, which were much higher than the national quality
      standard. The values suggested that the PM2.5 pollution was relatively serious in
      Hangzhou City, yet it has been improved when compared with the results of 2004.
      The toxic equivalent quantities (TEQs) of PCDD/Fs in PM2.5 were in the range of
      0.277-0.488 pg I-TEQ/m3, which were much higher than the results in 2004.
      Octachlorodibenzo-p-dioxin (OCDD) accounted for a large proportion to the total
      concentrations in PCDD/Fs, while 2,3,4,7,8-pentachlorodibenzofurans (2,3,4,7,8
      PeC- DF) contributed the highest to the TEQ. The values of PCBs and dioxin-like
      PCBs (DL-PCBs) varied from 2.9-8.1 pg/m3 and 2.6-6.1 fg WHO-TEQ/m3, respectively.
      PCB-28 was the most abundant contributor to the concentrations of PCBs, while PCB
      126 contributed the highest to the TEQ of DL-PCBs. Gas-particle distributions of
      PCDD/Fs and PCBs shows that PCDD/Fs were mainly distributed in the particle
      phase, but PCBs were preferably adsorbed in the gas phase.

PMID- 25752087
TI  - [Determination of mono- to tri-chlorinated dibenzo-p-dioxins and dibenzofurans in
      stack gas using isotope dilution high resolution gas chromatography-high
      resolution mass spectrometry].
AB  - A method for the determination of mono- to tri-chlorinated dibenzo-p-dioxins and
      dibenzofurans (mono- to tri-CDD/Fs) in stack gas using isotope dilution high
      resolution gas chromatography-high resolution mass spectrometry (HRGC-HRMS) was
      developed. The sam- ples were extracted by Soxhlet extraction, and then the
      extracts were concentrated and purified using a multilayer silica gel column and
      a basic alumina column. The analytes were separated by HRGC on a DB-5MS column
      (30 m x 0.25 mm x 0.25 MUm) and determined by HRMS. The identi- fication of mono-
      to tri-CDD/Fs was based on the retention times of 13C-labelled standard and the
      abundance ratios of the two exacted mass-to-charge ratios. The quantitative
      analysis was performed using the ratios of the integrated areas of the 13C
      labelled standards. This method had the recoveries ranging from 66.6% to 112.5%
      and the relative standard deviations (RSD) ranging from 19.9% to 40.5% (n = 5).
      The limits of detection (LODs) of this method for the mono- to tri-CDD/Fs were
      ranging from 0.027 to 0.485 MUg/L. Three stack gas samples from waste
      incinerators were measured using this method, with the recoveries ranging from
      85.7% to 137.0% and the concentrations ranging from 11.4 to 9,183 pg/Nm3. The
      results indicated that the method can be applied to the precise determination of
      mono- to tri-CDD/Fs at trace level in stack gas.

PMID- 25752088
TI  - [Analysis of polycyclic aromatic hydrocarbons in air samples by gas
      chromatography-triple quadrupole mass spectrometry].
AB  - A method of gas chromatography coupled to triple quadrupole tandem mass
      spectrometry (GC-MS/MS) has been optimized for the determination of polycyclic
      aromatic hydrocarbons (PAHs) in air samples. In the analysis step, isotope
      dilution was introduced to the quantification of PAHs. The GC-MS/MS method was
      applied to the analysis of the real air samples around a big petrochemical power
      plant in South China. The results were compared with those obtained by gas
      chromatography coupled to mass spectrometry (GC-MS). The results showed that
      better selectivity and sensitivity were obtained by GC-MS/MS. It was found that
      the external standard of deuterated-PAHs and internal standard of hexamethyl
      benzene were disturbed seriously with GC-MS, and the problems were both solved
      effectively by GC-MS/MS. Therefore more accurate quantification results of PAHs
      were obtained with GC-MS/MS. For the analysis of real samples, the RSDs of
      relative response factors ranged from 2.60% to 15.6% in standard curves; the
      recoveries of deuterated-PAHs ranged from 55.2% to 82.3%; the recoveries of
      spiked samples ranged from 98.9% to 111%; the RSDs of parallel specimens ranged
      from 6.50% to 18.4%; the concentrations of field blank samples ranged from not
      detected to 44.3 pg/m3; and the concentrations of library blank samples ranged
      from not detected to 36.5 pg/m3. The study indicated that the application of GC
      MS/MS on the analysis of PAHs in air samples was recommended.

PMID- 25752089
TI  - [Uncertainty evaluation of the determination of toxic equivalent quantity of
      polychlorinated dibenzo-p-dioxins and dibenzofurans in soil by isotope dilution
      high resolution gas chromatography and high resolution mass spectrometry].
AB  - Polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs) in soil samples
      were analyzed by isotope dilution method with high resolution gas chromatography
      and high resolution mass spectrometry (ID-HRGC/HRMS), and the toxic equivalent
      quantity (TEQ) were calculated. The impacts of major source of measurement
      uncertainty are discussed, and the combined relative standard uncertainties were
      calculated for each 2, 3, 7, 8 substituted con- gener. Furthermore, the
      concentration, combined uncertainty and expanded uncertainty for TEQ of PCDD/Fs
      in a soil sample in I-TEF, WHO-1998-TEF and WHO-2005-TEF schemes are provided as
      an example. I-TEF, WHO-1998-TEF and WHO-2005-TEF are the evaluation schemes of
      toxic equivalent factor (TEF), and are all currently used to describe 2,3,7,8 sub
      stituted relative potencies.

PMID- 25752090
TI  - [Identification of two interference peaks during dioxin analysis for biological
      samples].
AB  - Two interference peaks which generally appeared in company with 13C labeled
      2,3,7,8-tetrachlorodibenzofuran (13C12-2,3,7,8-TCDF) in the same ion channel
      during dioxin analysis for biological samples were identified using high
      resolution gas chromatography/high resolution mass spectrometry (HRGC/HRMS) and
      high resolution gas chromatography/low resolution mass spectrometry (HRGC/LRMS).
      It was firstly inferred that the interference peaks should be the two isomers of
      dichlorodiphenyldichloroethylene (DDE), which was a breakdown product of
      dichlorodiphenyltrichloroethane (DDT), one of the typical organic chlorine
      pesticides (OCPs). Thereafter, the standard solution of DDE including o,p'-DDE
      and p,p'-DDE was analyzed for confirmation. By evaluation of the peak separation
      in HRGC/HRMS, comparison of the GC retention times and ion abundance ratios of
      the two interference peaks in real samples with the two DDE isomers in standard
      solution, the interference peaks were finally confirmed as o,p'-DDE and p,p'-DDE
      in sequence on a DB-5MS column. This study provided valuable information for
      accurate identification of dioxin compounds during the biological sample
      analysis.

PMID- 25752091
TI  - [[Advances on sample pretreatment and analytical method for the analysis
      heterocyclic amines in meat products]].
AB  - Heterocyclic amines (HAs) are considered as highly potential mutagens and
      carcinogens in cooked meat products. Efficient sample pretreatment as well as
      sensitive analytical method is very important for the determination of HAs in
      complex samples. In this paper, some sample pretreatment methods such as solvent
      extraction, solid-phase extraction, and solid- phase microextraction as well as
      analytical methods including liquid chromatography, and liquid chromatography
      mass spectrometry are reviewed; The progress of HAs analysis is also prospected.
      A total of 51 references are cited.

PMID- 25752092
TI  - [[Preparation of boronate affinity sorbent and its extraction performance for
      benzoylurea pesticides]].
AB  - A new boronate affinity monolithic material was prepared and used as the
      extraction medium of stir cake sorptive extraction (SCSE). The porous boronate
      affinity sorbent was prepared by in situ copolymerization of 3
      acrylamidophenylboronic acid (APB) and divinyl benzene (DVB). To achieve optimum
      extraction performance for benzoylurea pesticides, several parameters, including
      desorption solvent, pH value, ionic strength in sample matrix, extraction and
      desorption times, were investigated in detail. At the same time, a simple,
      sensitive and environment friendly method for the determination of benzoylurea
      pesticides in water and juice samples was developed by the combination of SCSE
      APBDVB with HPLC equipped with a diode array detector. Under the optimized
      experimental conditions, the limits of detection (S/N = 3) for target analytes
      were 0.055-0.11 MUg/L in water and 0.095-0.31 MUg/L in juice. The precision of
      the proposed method was evaluated in terms of intra- and inter-assay
      repeatability calculated as RSD, and it was found that the RSDs were all below
      9.0%. The developed method was successfully applied to the determination of
      benzoylurea pesticide residues in water and juice samples and satisfactory
      recoveries of spiked target compounds were in the range of 75.6%-109%. The
      results well demonstrate that the new sorbent can extract benzoylurea pesticides
      effectively through multi-interactions including boron-nitrogen coordination,
      hydrogen-bond and hydrophobic interactions between sorbent and analytes.

PMID- 25752093
TI  - [Simultaneous determination of 11 bisphenols in plastic bottled drinking water by
      ultra performance liquid chromatography-tandem mass spectrometry].
AB  - A sensitive method was developed for the simultaneous determination of 11
      bisphenols in plastic bottled drinking water by ultra performance liquid
      chromatography-tandem mass spectrometry (UPLC-MS/MS). The samples were freeze
      dried under vacuum and then dissolved with methanol. The separation was performed
      on a UPLC BEH C18 column (100 mm x 2.1 mm, 1.7 MUm) by using 0.1% (v/v) NH3 . H2O
      and methanol as mobile phases with gradient elution at a flow rate of 0.2 mL/min.
      The electrospray ionization (ESI) source in negative ion mode was used for the
      analysis of the 11 bisphenols in the multiple reaction monitoring (MRM) mode. The
      results verified that the standard curves for the 11 bisphenols were obtained
      with good correlation coefficients (R2) > 0.997 in their concentration ranges.
      The limits of detection (LOD, S/N = 3) for the 11 bisphenols were in the range of
      0.01-1.00 MUg/L. The mean recoveries for the 11 bisphenols at three spiked levels
      (low, middle, high) were 75.3%-102.1% with the relative standard deviations of
      1.5%-8.9%. Seven plastic bottled drinking water samples were tested, and no
      bisphenol was found. The method is accurate, simple, rapid and feasible for the
      simultaneous determination of bisphenols in plastic bottled drinking water.

PMID- 25752094
TI  - [Simultaneous determination and screening of five pigments in marine
      phytoplanktons by high performance liquid chromatography-triple quadrupole mass
      spectrometry].
AB  - A quantitative method based on high performance liquid chromatography coupled
      with electrospray ionization tandem triple-quadrupole mass spectrometry (HPLC-ESI
      QqQ-MS) has been established for five pigments in marine phytoplanktons. The HPLC
      method used ternary solvent systems and a reversed-phase C16-amide column. In
      addition, methanol, acetonitrile and aqueous ammonium acetate were used as mobile
      phases. Five pigments (chlorophyll a, chlorophyll b, beta, beta-carotene, lutein
      and fucoxanthin) were quantified in selective reaction mode. As results, good
      linear relationships were achieved between the concentrations and the peak areas
      of the five pigment standards. And their correlation coefficients (r2) were
      higher than 0.996. The recoveries of the pigment standards were between 82.77%
      and 99.83%. The inter-day and intra-day precisions were lower than 5% (n = 5).
      The detection limits of the pigments for this method were between 0.02 and 0.16
      MUg/L and the quantification limits were in the range from 0.06 to 0.54 MUg/L.
      According to the above method, eleven algae (Heterosigma akashiwo (NMBRah03-2),
      Heterosigma akashiwo (NMBRah03-2-2), Karlodinium veneficum (NMBjah047-1),
      Prorocentrum minimum ( NMBjah042), Nannochloropsis oceanic (NMBluh014), Chlorella
      pyrenoidosa (NMBluh015-1), Pleurochrysis sp. (NMBjih026-1), Prymnesium sp.
      (NMBjih029), Skeletonema costatum (NMBguh004-1), Thalassiosira weiss- flogii
      (NMBguh021) and Thalassiosira pseudonana) (NMBguh005)) have been investigated for
      comparing the pigment distributions. The method is sensitive, accurate,
      reproducible, and useful for the study of alga compositions.

PMID- 25752095
TI  - [Determination of 11 industrial antioxidants in the aqueous simulants by ultra
      performance liquid chromatography-tandem mass spectrometry].
AB  - An ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS)
      method has been developed to identify and determine 11 industrial antioxidants in
      the aqueous simulants. A ProElut PLS SPE column was used for the enrichment, and
      an ACQUITY UPLC BEH C18 UPLC column (100 mm x 2.1 mm, 1.7 MUm) was used for
      separation by the gradient elution with pure water and acetonitrile as the mobile
      phases. The MS/MS detection was performed with an electrospray ionization (ESI)
      source in negative mode. The external standard method was used for quantitation
      in the present study. The linear ranges of the 11 analytes were from 5.0 to 100
      MUg/L. The coefficients of correlation were greater than 0.995. The recoveries of
      blank aqueous simulants fortified with the 11 analytes at the levels of 5.0, 10.0
      and 20.0 MUg/L were 61.4% to 109.4% with the relative standard deviations varied
      from 3.9% to 18.2% (n = 6). The LODs and LOQs of the 11 analytes in aqueous
      simulants were 0.2-1.0 MUg/L and 0.5-3.0 MUg/L, respectively. This method is
      highly sensitive and accurate, and can be applied to the determination of the 11
      trace industrial antioxidants in the aqueous simulants.

PMID- 25752096
TI  - [Identification of banned aromatic amines and their isomers in textiles by ultra
      performance liquid chromatography-linear ion trap/orbitrap high resolution mass
      spectrometry].
AB  - A method of ultra-performance liquid chromatography-linear ion trap/orbitrap high
      resolution mass spectrometry (UPLC-LTQ/Orbitrap MS) was used to screen and
      confirm 24 banned aromatic amines and their 14 isomers at the same time. The main
      factors influencing the separation including the column, and the nature of make
      up solvent were optimized. Under the optimized experimental conditions, the
      analytes were reduced to banned aromatic amine with sodium dithionite, extracted
      by methyl tert-butyl ether and loaded onto a ZORBAX SB-C18 column (150 mm x 2.1
      mm, 5 MUm) with a gradient elution of methanol and 0.1% formic acid aqueous
      solution, and finally detected by LTQ/Orbitrap MS. The screening and quantitative
      analysis were carried out by the accurate mass of quasi-molecular ion and the
      peak in extracted chromatogram with accurate mass. The correlation coefficients
      were higher than 0.99 and the limits of detection were in the range of 0.5-5
      MUg/kg. The method could screen and confirm the 24 banned aromatic amines and
      their 14 isomers at the same time. The results were 1.56 mg/kg of 4
      chloroaniline, 0.34 mg/kg of o-toluidine, and 0.81 mg/kg of 2,6-toluylenediamine
      with the relative standard deviations ranging from 0.27% to 1.32% in actual
      samples. The results indicate that the developed method is simple, efficient and
      precise, and can be a reliable technique for the separation of the 24 banned
      aromatic amines and their 14 isomers in textile samples.

PMID- 25752097
TI  - [[Chiral separation of five arylpropionic acid drugs and determination of their
      enantiomers in pharmaceutical preparations by reversed-phase high performance
      liquid chromatography with cellulose-tris-(4-methylbenzoate) stationary phase]].
AB  - Chromatographic behaviors for enantiomeric separation of arylpropionic acid drugs
      were systematically developed by reversed phase-high performance liquid
      chromatography (RP-HPLC) using cellulose-tris-(4-methylbenzoate) (CTMB) as chiral
      stationary phase (CSP). The effects of the composition of the mobile phase,
      additives and temperature on chiral separation of flurbiprofen, pranoprofen,
      naproxen, ibuprofen and loxoprofen were further investigated. The enantiomers had
      been successfully separated on CSP of CTMB by the mobile phase of methanol-0.1%
      (v/v) formic acid except naproxen by acetonitrile-0.1% (v/v) formic acid at 25 
      degrees C. The mechanisms of the racemic resolution for the above mentioned five
      drugs are discussed thermodynamically and structurally. The resolutions between
      respective enantiomers for arylpropionic acid drugs on CTMB had significant
      differences due to their chromatographic behaviors. The order of resolutions
      ranked pranoprofen, loxoprofen, flurbiprofen, ibuprofen and naproxen. The method
      established has been successfully applied to the determination of the enantiomers
      of the five drugs in commercial preparations under the optimized conditions. It
      proved that the method is simple, reliable and accurate.

PMID- 25752098
TI  - [A peak recognition algorithm designed for chromatographic peaks of transformer
      oil].
AB  - In the field of the chromatographic peak identification of the transformer oil,
      the traditional first-order derivative requires slope threshold to achieve peak
      identification. In terms of its shortcomings of low automation and easy
      distortion, the first-order derivative method was improved by applying the moving
      average iterative method and the normalized analysis techniques to identify the
      peaks. Accurate identification of the chromatographic peaks was realized through
      using multiple iterations of the moving average of signal curves and square wave
      curves to determine the optimal value of the normalized peak identification
      parameters, combined with the absolute peak retention times and peak window. The
      experimental results show that this algorithm can accurately identify the peaks
      and is not sensitive to the noise, the chromatographic peak width or the peak
      shape changes. It has strong adaptability to meet the on-site requirements of
      online monitoring devices of dissolved gases in transformer oil.

PMID- 25752099
TI  - [Neonatal hearing screening: 0136F experiences].

PMID- 25752100
TI  - [Newborn hearing combined gene screening--China model and future development].

PMID- 25752101
TI  - [Diagnosis and prevention of genetic deafness: progress and attention].

PMID- 25752102
TI  - [Analysis the relationship between SLC26A4 mutation and current diagnosis of
      inner ear malformation in children with sensorineural hearing loss].
AB  - OBJECTIVE: Explore the relationship between the pathogenic mutations of SLC26A4
      gene and inner ear malformation, and analyze the feasibility of genetic testing
      to help current diagnosis in part of children with sensorineural hearing loss.
      METHOD: 2094 cases of children were detected by SLC26A4 with the method of DNA
      sequence. CT phenotypes of those children were classified according to the method
      proposed by Sennaroglu. We analyzed the relationship between the pathogenic
      mutations of gene and the CT phenotypes. RESULT: (1) 685 cases of inner ear
      malformations were found in 2094 cases of children with sensorineural hearing
      loss by CT examination (371 cases of cochlea malformation were consisted of the
      follow types of malformation. Michel deformity was 6 cases, cochlea aplasia was 8
      cases, common cavity deformity was 12 cases, incomplete partition type I was 27
      cases, cochlea hypoplasia was 30 cases and Mondini malformation was 288 cases);
      Vestibular aqueduct was 265 cases; Vestibular/semicircular canal/internal
      auditory canal were 49 cases, normal was 1409 cases. (2) The DNA sequence results
      revealed that 465 cases carried pathogenic mutations (Bi-allelic mutations) of
      SLC26A4 gene, among which 135 cases were homozygous, 330 cases were compound
      heterozygous. (3) Pathogenic mutations of SLC26A4 gene detected 100% (465/465) in
      the group related to vestibular aqueduct malformation. CONCLUSION: The results
      suggest that pathogenic mutation of SLC26A4 gene is closely related to the CT
      phenotype of vestibular aqueduct malformation. Detecting of pathogenic mutations
      for hearing loss is binging the possibility to identify children with inner
      malformations at an early stage. As a consequence, it will improve the current
      diagnosis and therapeutical option.

PMID- 25752103
TI  - [The study of GJB2 dominant mutaion distribution in Chinese deafness patient and
      the analysis of phenotype].
AB  - OBJECTIVE: Mutations in the GJB2 are the most common cause of nonsyndromic
      autosomal recessive sensorineural hearing loss. A few mutations in GJB2 have also
      been reported to cause dominant nonsyndromic or syndromic hearing loss. This
      study analysised the GJB2 dominant mutation in Chinese deafness. METHOD: 1641
      patients as GJB2-related hearing loss were enrolled, summarized the type of
      dominant mutaion, analyzed the hearing level and other systerm lesion. RESULT:
      Nine probands with severe-profound hearing loss were diagnosed as GJB2 domiant
      mutation (R75W,G130V, R143Q,p. R184Q). And one patient with R75W mutation was
      diagosed as hearing loss and palmoplantar keratoderma. CONCLUSION: GJB2 dominant
      mutation can cause severe-to-profound bilateral sensorineural hearing impairment
      and not common with syndromic hearing loss in Chinese deafness.

PMID- 25752104
TI  - [Early diagnosis and intervention in 0-9 months old infants with hearing loss].
AB  - OBJECTIVE: To investigate the current situation of early diagnosis and
      intervention in 0-9 months old infants with hearing loss and analysis factors
      that will affect early diagnosis and intervention. METHOD: One hundred and eighty
      six infants referred to the West China hospital from February 2014 to September
      2014 were included. All 186 children were referred due to the fact that either
      they failed infant hearing screening or outer ear malformation. Early diagnosis
      and/or intervention were performed on those 186 children and their records of
      early diagnosis and intervention were analyzed. RESULT: Among the 186 infants,
      167 (89.8%) were diagnosed with an average age at (4.0 +/- 1.4) months. Among the
      167 infants with final diagnosis, there were 31 (18.6%) infants diagnosed as
      conductive hearing loss (CHL), and 99 cases (59.3%) diagnosed as sensorineural
      hearing loss (SNHL), among whom, there were 75 (44.9%) bilateral SNHL and 24
      (14.4%) unilateral SNHL. There were 2 cases (1.20%) with SNHL on one side and
      atresia on the other side. 5 (2.99%) of all conductive hearing loss cases with
      unilateral atresia and 2 cases with auditory neuropathy (AN) were found. 33
      infants (19.8%) were found to have normal hearing. 30.7% (23/75) infants
      diagnosed as bilateral SNHL and 8.3% (2/24) infants diagnosed as unilateral SNHL
      were fitted with hearing aids. The fitting rate in infants with bilateral SNHL
      with mild, moderate, severe to profound degrees were 0 (0/23), 24.0% (6/25),
      66.7% (6/9), 61.1% (11/18) respectively. The average intervention age was (5.0 +/
      2.1) months. CONCLUSION: Although the early diagnosis and intervention situation
      in this study are very close to international standard, there are still infants
      without final diagnosis and infants with hearing loss without hearing aid
      fitting. Further studies and efforts to promote early diagnosis and intervention
      in infants with hearing loss are needed.

PMID- 25752105
TI  - [Thinking of newborn hearing screening and children hearing care].

PMID- 25752106
TI  - [Analysis the relationship between the found ways and first diagnosis age for
      large vestibular aqueduct children].
AB  - OBJECTIVE: To explore the found ways and first diagnosis age of children with
      large vestibular aqueduct, and their relations with hearing loss. METHOD: Medical
      histories of 122 cases of children diagnosed with large vestibular aqueduct by
      HRCT or MRI had been collected from January 2009 to April 2014 in our hospital
      children's hearing diagnosis center clinic. Found ways comprise of accepting
      universal newborn hearing screening (UNHS) group and unaccepting UNHS group.
      Accepting UNHS children were divided into two ears unpassing group, single ear
      unpassing group and passing group. The patients in unaccepting UNHS group were
      divided into not sensitive to sounds, speech stunting, sudden hearing loss, and
      other group. Analysis the relationship between the found ways and first diagnosis
      age and their relations with hearing loss. RESULT: There are 84 cases (68.85%)
      accepting UNHS, the average age of first diagnosis was (17.24 +/- 17.08) months;
      37 cases (31.15%) are not accepting UNHS. The average age of first diagnosis was
      (30.92 +/- 18.21) months. The average first diagnosis age of accepting UNHS group
      was more earlier than the unaccepting UNHS group. The difference was
      statistically signif- icant (P < 0.01). There were 57 cases (67.85%) whose two
      ears not pass UNHS; 15 cases (17.86%) single ear not pass; namely the referral
      rate was 85.71%; 12 cases (14.29%) pass the test. The first diagnosis age of
      passing UNHS group was more later than two ears unpassing group (P < 0.001). In
      the unaccepting UNHS group, the average first diagnosis age of not sensitive to
      sounds group (19.69 +/- 11.16 months) was more earlier than words dysplasia group
      (37.13 +/- 15.62 months) and sudden hearing loss group (47.40 +/- 24.70 months)
      (P < 0.01). The difference in the degree of hearing loss between accepting UNHS
      and unaccepting UNHS group had no statistical significance (P > 0.05). In
      unaccepting UNHS group ,the average first diagnosis age of the mild-to-moderate
      hearing loss group was later than the very severe hearing loss group (P < 0.01).
      CONCLUSION: Most of large vestibular aqueduct children can be found and receive
      diagnosis early by UNHS. But part of these patients with late-onset or
      progressive hearing loss, especially these with mild-to-moderate hearing loss
      cannot be found early, which should arouse our attention.

PMID- 25752107
TI  - [Eustachian tube balloon dilation in eustachian tube dysfunction related
      diseases].
AB  - OBJECTIVE: To investigate the effect of Eustachian tube balloon dilation (ETBD)
      in treatment of eustachian tube related diseases. METHOD: Fifteen cases (20 ears)
      of otitis media with effusion and 22 cases (30 ears) of symptomatic Eustachian
      tube dysfunction were recruited. Technique of tubomanometry (TMM) showed
      obstructive Eustachian tube dysfunction in all patients. All the patients were
      received ETBD and followed up with VAS evaluation of ear fullness, muffled
      hearing, poping sound in the ear and tinnitus. And also the TMM change and middle
      ear effusion. RESULT: Ear fullness, muffled hearing released with 1 week (ear
      fullness: 8.2 +/- 1.4 vs. 2.0 +/- 1.2, P < 0.05, muffled hearing: 6.2 +/- 1.2 vs.
      3.1 +/- 0.8, P < 0.05). No recurrence was seemed within 6 months. The eustachian
      function test turned better. Symptomatic Eustachian tube dysfunction had an
      effective rate of 96.6% while otitis media with effusion was 95.0%. CONCLUSION:
      ETBD have good short-term effect in obstructive eustachian tube dysfunction
      related middle ear dysfunction, which might provide a good way to solve the
      eustachian tube related diseases.

PMID- 25752108
TI  - [The effectiveness of endoscopic tragus cartilage-perichondrium myringoplasty in
      the treatment of large tympanic membrane perforations].
AB  - OBJECTIVE: To evaluate effectiveness of endoscopic tragus cartilage-perichondrium
      in the treatment of large tympanic membrane perforations. METHOD: Patients with
      large tympanic membrane perfortations who had underwent cartilage-perichondrium
      myringoplasty were retrospectively retrieved from our department. Those with a
      follow-up of equal to or greater than 12 months after surgery were included in
      the study. Hearing test results were reported using a four-frequency air
      conduction and bone-air conduction gap. Patients were labeled as treatment
      success if the tympanic membrane was intact without lateralization or anterior
      blunting after surgery. RESULT: Of the 35 patients with large tympanic membrane
      perforations treated by endoscopic tragus cartilage-perichondrium, 33 (94.3%)
      were treatment success. There was no graft lateralization, anterior blunting,
      neocholesteatoma, and sensorineural hearing loss in these patients after surgery.
      The air conduction and bone-air conduction gap before surgery in the study cohort
      were (43.8 +/- 5.7) dB and (28.5 +/- 3.1) dB, respectively. Postoperative air
      conduction and bone-air conduction gap of the cohort were (31.4 +/- 6.4) dB HL
      and (16.2 +/- 4.1) dB, respectively. The postoperative air conduction and bone
      air conduction gap decreased significantly after surgery (P < 0.01). Overall
      postoperative air-bone gap in 27 of the 35 patients (77%) were less than 20 dB
      after surgery. CONCLUSION: Endoscopic cartilage-perichondrium myringoplasty is an
      effective procedure in the treatment of large tympanic membrane perforations.

PMID- 25752109
TI  - [Application of negative pressure drainage on nasal septum recons tructomy by
      endoscopic].
AB  - OBJECTIVE: To investigate the clinical effect of negative pressure drainage after
      septum surgery. METHOD: One hundred and two cases with septum deviation were
      randomly divided into two groups, i. e. experimental group and controlling one.
      With 51 cases in each. Degree of comfort and complication of two groups were
      compared. RESULT: The cases in experimental group showed significantly relieved
      postoperative reaction with negative pressure drainage, when compared with that
      of controls, the incidence of complication were not increased. CONCLUSION:
      Negative pressure drainage can be taken as one of the ideal materials for
      hemostasia after septum surgery.

PMID- 25752110
TI  - [Cochlear implant operation to summarize and postoperative outcome].
AB  - OBJECTIVE: The aim of this study was to evaluate the clinical features of
      cochlear reimplantation. To review our experience of cochlear reimplant surgery.
      METHOD: Retrospective analysis of all 25 cochlear reimplant surgeries between
      2002 and 2012. Causes of revision operations, number of electrode channels
      inserted, surgical findings and postoperative speech performances were analyzed.
      RESULT: Causes of reimplantation were eight hard failures; eight poor implanted
      electrodes position, four poor outcome, three skin flap infection lead to implant
      device exposure, one postoperative symptoms of facial nerve stimulation, one
      postoperative temporal bone lesions. All cochlear reimplantations were
      successfully performed in our hospital, audiologic performances were stable or
      improved following reimplantation in most of cases. CONCLUSION: Cochlear implant
      surgeons should have a good knowledge of how to diagnose cochlear implant
      failures and how to deal with medical complications related to cochlear
      implantation. Medical and audiologic outcomes are generally excellent. Cochlear
      reimplantation appears to be a safe and effective.

PMID- 25752111
TI  - [Evaluate the related factors of recurrence after carbon dioxide laser in
      treatment of early glottic carcinoma].
AB  - OBJECTIVE: To analyze the recurrencerelative factors of early glottic carcinoma
      after carbon dioxide laser treatment. METHOD: A retrospective analysis of 134
      early glottic carcinoma patients' clinical data was taken to analyze the
      relationships between recurrence and gender, age, pathologic degree, T stage,
      involvement of anterior commissure and involvement of thyroarytenoid muscle.
      RESULT: Recurrent ratio of well-differentiated, middle-differentiated and poorly
      differentiated squamous cell carcinoma were 11.83%, 18.42% and 33.33% (P > 0.05)
      respectively. Recurrent ratio of T1a, T1b, T2 were 13.24%, 18.92%, 23.08% (P >
      0.05) respectively. The recurrent rate was 33.33% of tumors offended the anterior
      commissure, versus 5.43% with no involvement of anterior commissure (P < 0.01).
      The recurrent rate was 59.09% of tumors offended the thyroarytenoid muscle,
      versus 5.36% with no involvement of thyroarytenoid muscle (P < 0.01). Unvaried
      and multivariate analysis indicated that the involvement of anterior commissure
      and the involvement of thyroarytenoid muscle were the factors of recurrence.
      CONCLUSION: Recurrence of early glottic carcinoma after carbon dioxide laser
      treatment is effected by the involvement of anterior commissure and the
      involvement of thyroarytenoid muscle. Resection can be performed conservatively
      according to evaluation of macroscopic tumour extension.

PMID- 25752112
TI  - [Tinnitus assessment by THI and VAS in patients with sudden sensorineural hearing
      loss].
AB  - OBJECTIVE: To verify the relationship between THI and VAS scores in patients with
      sudden hearing loss and tinnitus in a prospective study. METHOD: Forty-four
      patients classified their tinnitus according to VAS and THI before and after
      treatment, and both scores were compared through the Pearson's correlation
      coefficient test and Nonparametric tests. RESULT: There was a correlation between
      VAS and THI scores in patients with sudden hearing loss and tinnitus. Tinnitus
      assessment scores were significantly reduced after treatment. Decreasing of THI
      and VAS scores were not depended on frequency and loudness of tinnitus and
      severity of deafness, but therapeutic effect of sudden sensorineural hearing
      loss. CONCLUSION: THI and VAS scores are useful for assessment of tinnitus in
      patients with sudden hearing loss and tinnitus.

PMID- 25752113
TI  - [Clinical significance of miRNA-204 in nasopharyngeal carcinoma].
AB  - OBJECTIVE: To investigate the expression of miRNA-204 in patients with NPC and to
      analyze the as- sociation of the expression with the cIinicopathologicaI features
      and prognosis. METHOD: The expression levels of miRNA-204 in 50 patients with NPC
      and 40 patients with nasopharyngeal chronic inflammation were detected by using
      stem-loop real-time reverse transcription-polymerase chain reaction RT-PCR.
      Analysis of the relationship between microRNA and prognosis by Kaplan-Meier
      method. RESULT: Expression levels of miRNA-204 were down- regulated in patients
      with NPC as compared with patients with nasopharyngeal chronic inflammation (P <
      0.05). The expression of miRNA-204 was associated with EBV infection,
      differentiation, lymphatic metastasis and TNM stages (P < 0.05). Low miRNA-204
      expression was significantly correlated with shorter overall survival (P < 0.05)
      of NPC. CONCLUSION: The downregulation of miRNA-204 expression has related with
      disease progression and miRNA-204 can serve as a potential therapeutic target for
      NPC.

PMID- 25752114
TI  - [The management of sinonasal inverted papilloma by endoscopic surgery: an
      analysis of 54 cases].
AB  - OBJECTIVE: The study is to evaluate our results of patients with sinonasal
      inverted papilloma (SIP) undergoing endoscopic sinus surgery and to investigate
      the recurrence relative factors of SIP. METHOD: A retrospec- tive analysis was
      performed of medical records for 54 cases SIP treated with endoscopic resection.
      Compared to pre operation imaging evaluation and intraoperative observation,
      efficacy assessments included endoscopy during follow-up after operation and
      combined with CT examination results. RESULT: The incidence of 54 cases with
      ethmoid sinus, part of the lateral wall of the nasal cavity was higher. The
      recurrence rate was higher in the cases invaded front and/or inferior wall of
      maxillary sinus, frontal recess. There was no case with middle turbinate.
      Canceration with the same time accounted for 1.85%. CONCLUSION: Misdiagnosis as
      polyps, the lesion sites of tumour, involving the frontal recess, front and
      inferior wall of maxillary sinus are the risk factors of recurrence. The
      preoperative accurate judgment of the primary tumor site and surgical resection
      completly are the most effective means of preventing recurrence. Postoperative
      endoscopy examination combined with CT examination is an effective means for the
      evaluation of recurrence.

PMID- 25752115
TI  - [The analysis of the correlation of tympanic injection of triamcinolone acetonide
      and middle ear pressure after radiotherapy].
AB  - OBJECTIVE: To analyze the correlation of the tympanic injection of triamcinolone
      acetonide, middle ear pressure (MEP) and radioactive secretory otitis media
      (RSOM) with nasopharyngeal carcinoma (NPC) after radiotherapy. METHOD: Fifty-two
      patients suffering NPC without otitis media before radiotherapy were randomly
      divided into three groups. 17 cases with 34 ears were distributed into treatment
      group I, and radiotherapy 1 hour before the start of each side of the tympanic
      cavity injection of triamcinolone acetonide injection, 1-7 weeks 1 times a week.
      Treatment group I had 17 cases with 34 ears,and radiotherapy 1 hour before the
      start of each side of the tympanic cavity injection of triamcinolone acetonide
      injection, 1-12 weeks 1 times a week. And control group consisted of 18 cases
      with 36 ears who didn't accept such treatment. In all 104 ears, MEP was tested at
      the begin of radiotherapy and the end of 1st, 2nd, 3rd month after radiotherapy.
      RESULT: From the beginning of radiotherapy to the end of th 1st, 2nd, 3rd month
      after radiotherapy, the morbidity of RSOM gradually increased and MEP decreased
      in the treatment group I , II and the control group, in which treatment group II
      showed the lowest morbidity of RSOM and MEP was maximum (P < 0.01), and the
      treatment group I showed the lower morbidity of RSOM and MEP was greater (P < 0.
      05), while the control group showed the highest morbidity of RSOM and MEP was
      minimum (P > 0.05). CONCLUSION: Tympanic injection of triamcinolone acetonide
      could reduce radiation injury, and medication time was positively correlated with
      the MEP, and a negative correlation with RSOM morbidity, and the longer
      treatment, the more significant the effect is. The difference is most obvious at
      the end of 3rd month after radiotherapy. It may be due to the more active
      repairation after radiation damage in middle ears, but long-term efficacy must
      continue to observe.

PMID- 25752116
TI  - [Beclomethasone dipropionate cream combined with He-Ne laser irradiation
      treatment of nasal vestibule eczema].
AB  - OBJECTIVE: To observe the clinical efficacy of nasal vestibule eczema by using
      beclomethasone dipropionate in combination with He-Ne laser therapy. METHOD: The
      200 cases of nasal vestibule eczema patients were randomly divided into treatment
      and control groups. The control group received the rub beclomethasone
      dipropionate cream treatment one time per day. The treatment group supplemented
      with He-Ne laser irradiation treatment on the basis of the control group on the
      same treatment, alsoone time per day. Then the results were analyzed. RESULT: The
      total effective rate was 100.0% in treatment group, while 75.0% in the control
      group. The difference between the two groups was statistically significant (P <
      0.05). CONCLUSION: Beclomethasone dipropionate cream combined with He-Ne laser
      irradiation therapy on nasal vestibule eczema is significant, and easily to
      operate, with significant anti-inflammatory, anti-itch, analgesic effects.

PMID- 25752117
TI  - [The expression levels of three T-type calcium channel receptors in inner ear of
      C57BL/6J mice with age].
AB  - OBJECTIVE: To explore the expression levels of three T-type calcium channel
      receptors (alpha1G; alpha1H; alpha1I) in the cochlea and spiral ganglion neurons
      of C57BL/6J mice with different ages. METHOD: Thirty cases of C57BL/6J mice were
      divided into three groups (6-8 W, 24-26 W, 42-44 W) according to the age. The
      expressions of three T-type calcium channel receptors were quantified by RT-PCR
      after hearing thresholds measured by ABR. RESULT: Three receptors were detected
      in the cochlea and spiral ganglion neurons of 6-8 W C57BL/6J mice. The
      quantitative results showed that the expression levels of alpha1H and alpha1I
      were highest among three receptors in spiral ganglion neurons and in the cochlea
      respectively. The expression levels of three receptors significantly decreased
      with age,especially at the age of 4244 W. CONCLUSION: The expression of T-type
      calcium channel receptors reduced with age in the inner ear of C57BL/6J mice.

PMID- 25752118
TI  - [Clinical analysis of treatment of earlap keloid].

PMID- 25752119
TI  - [Effect observation of the three steps self-modified canalith repositioning in
      the treament of posterior semicicular canal BPPV].

PMID- 25752121
TI  - [Middle ear cholesteatoma on the condition of ear and influence on the operation
      of choice].

PMID- 25752120
TI  - [Temporal bone CT digital on chronic suppurative otitis media with cholesteatoma
      navigation assessment].

PMID- 25752122
TI  - [Therapy experience of purulent otorrhea ear fungus infection].

PMID- 25752123
TI  - [One cases of cervical esophageal fistula].
AB  - Twenty days after the operation of anterior cervical decompression fusion with
      internal fixation, the fistula was found at the lower end of right neck incision
      with purulent secretion, the intumescent mucosa was founded at the posterior wall
      of the esophagus, down about 5 cm of the oesophagostomum. The metal plate sample
      exposed under the intumescent mucosa. The diagnosed was "neck esophageal
      fistula".

PMID- 25752124
TI  - [Analysis of six cases concerning clinical features of rhinolith].
AB  - To analyze six cases concerning clinical features, the treatment process and
      curative effect of Rhinolith. The six patients had unilateral nasal obstruction,
      three of them were accompanied with purulent nasal discharge, two had blood with
      them, one patient had repeated hemorrhage of nasal cavity and two patients had
      developed headache. By using endoscopic, four irregular stones which are yellow,
      gray and brown were found in the middle and back end. Because of the severe nasal
      septum deviation and inferior turbinate polypoid, the stone could not be seen
      clearly but could be touched by aspirator. In sinus CT examination of 6 cases, it
      showed incomplete irregular shapes and had high density unilateral nasal cavity
      in the posterior segment. 4 patients had nasal deviation, 3 patients had
      ipsilateral sinusitis. 4 patients removed their stone by using endoscopy, 2
      patients took the stone away after correction of nasal septum. Pathologic
      diagnosis: rhinolith. Two patients also had exogenous foreign matters which were
      considered as pseudo nasal stones.

PMID- 25752125
TI  - [Missed diagnosis in 1 case of esophageal foreign body of button battery in
      infant: a case report and review of the literature].
AB  - To be on the alert on infants with esophageal foreign body, and to pay more
      attention to the button battery esophageal foreign body, the clinical data of a
      12-month-old infant with button battery esophageal foreign body, which was missed
      diagnosis for up to 4 months, is analyzed. And the related literature is
      reviewed. An esophagoscopy was carried out to remove the foreign body. A
      favorable outcome was achieved. When the infants have unexplained
      gastrointestinal symptoms, we should consider the possibility of an esophageal
      foreign body. We should pay attention to the button battery due to its highly
      corrosive to the esophagus. Timely diagnosis, reasonable operation are the keys
      to cure.

PMID- 25752126
TI  - [Pilomatricoma behind and below the ear: one case report].
AB  - A 6 years old boy came to our department with a complaint of a growing goitre
      behind and below the right ear that started 4 years ago. Clinical features: there
      was a 2.0 cm x 1.5 cm nontender goitre behind and below the right ear, protruding
      from the skin with clear boundary. The temperature and color of the skin covered
      the goitre were normal. B-mode ultrasound features: there was a mass under the
      skin with the size of 2.0 cm x 0.8 cm showing strong echo. The borders of the
      mass were unclear, and no signal of blood flow was detected. Pathology diagnosis:
      pilomatricoma.

PMID- 25752127
TI  - [Vestibular schwannoma: a case report of misdiagnosis].
AB  - Vestibular schwannoma is a rare tumor, which is easily misdiagnosed. The authors
      presented a case of vestibular schwannoma in a 36-year-old woman. The clinical
      manifestations were recurrent vertigo, hearing loss of the left ear, and
      tinnitus. The pure tone audiometry threshold of the left ear was 45dBHL with air
      conduction, and 33 dBHL with bone conduction. A CT scan of the temporal bone
      region didn't show any abnormal finding. A MRI scan of the head showed nodule
      abnormal signal in the internal of left vestibular and the narrow of
      perilymphaticum gap in T2W1 + T2Flair. The initial diagnosis was Meniere's
      disease. And the post-operation pathologic diagnosis was vestibular schwannoma.

PMID- 25752128
TI  - [Tympanosclerosis etiology and treatment].
AB  - SUMMARY: Tympanosclerosis is the middle ear tissue hyalinization and
      calcification caused by chronic middle ear inflammation, which mainly results in
      conductive deafness with unobvious clinical symptom. Etiology is unclear. The
      treatment is given priority to surgical treatment at present, while long-term
      effect reported mostly poor. This article analyzed etiology and treatment of the
      tympanic cavity sclerosis.

PMID- 25752129
TI  - [Next-generation sequencing in molecular diagnosis of hereditary hearing loss].
AB  - Next-generation sequencing (NGS) technologies have improved as well as the costs
      have gradually decreased in the detections of genetic diseases. This article
      describes the principle, platform, and data analysis of NGS and the application
      of NGS technologies to the molecular diagnosis of hereditary hearing loss (HL).
      The use of NGS technologies makes the discovery of HL genes more feasible than
      ever. And the data obtained by NGS used in genetic counseling for clinical
      practice may assist in defining genetic profiles of HL individuals and expedite
      the pace of personalized medical care.

PMID- 25752130
TI  - [The in vitro refolding of beta-barrel outer membrane protein of gram-negative
      bacteria--a review].
AB  - A cell of gram-negative bacteria is surrounded by two layers of membrane, the
      inner membrane and the outer membrane. Proteins are the major composition of
      outer membrane. Many outer membrane proteins carry a trans-membrane beta-barrel
      structure that formed by multiple anti-parallel beta-strands connected with
      hydrogen bonds. These proteins can act as porins, transporters, enzymes,
      receptors, virulence factors and structural proteins. Therefore, their correct
      folding and membrane integration are important for the survival of gram-negative
      bacteria. Most beta-barrel outer membrane proteins could be easily expressed
      recombinantly and refolded in vitro under certain conditions. The in vitro
      folding processes could be monitored and investigated through many ways, which
      makes outer membrane proteins become a model system to study the effects of
      abiotic and biological factors on the folding of membrane proteins. In this
      article, the research progress on the in vitro refolding of outer membrane
      proteins are reviewed from the aspects of refolding methods, the factors that
      affect folding processes and experimental methods. Finally, the research
      prospects in this field are discussed.

PMID- 25752131
TI  - [Phenotypic and molecular characteristics of Salmonella enterica serotype 1,4,
      [5] ,12:i:--a review].
AB  - Salmonella enterica serotype 1, 4, [5 ], 12: i:- ( Salmonella 1, 4, [5], 12: i:
      ), an emerging serotype antigenically related to Salmonella Typhimurium (1,4,
      [5], 12 : i:1,2) but lacking the second phase flagellar antigen, has been
      frequently detected in many countries over the last 10 years. Nowadays it seems
      to be one of the major serotypes responsible for human salmonellosis cases
      worldwide. In addition, multidrug resistance is quite common in Salmonella 1, 4,
      [5],12:i:-, the two major clones (labelled as Spanish and European clones) show
      multidrug resistance to four or more unrelated classes of antimicrobials mediated
      by plasmids or chromosome. Some resistance determinants including bla(TEM),
      bla(CTX-M(-1), aac(3)-IV, aadA2, cmlA1, sul1, sul2, dfrA12, strA-strB, tet (A)
      and tet (B) have been found in these multidrug resistance strains. The genomic
      characterization of 1,4, [5] ,12:i:- isolates suggests that this serovar is
      likely to gather several clones or strains that have independently emerged from
      S. Typhimurium, and have changed through multiple independent events involving
      different clonal groups. In later study, emphasis should be paid on development
      of rapid and precise detection methods and study of pathogenic and resistance
      mechanisms of Salmonella 1,4, [5] ,12:i:-.

PMID- 25752132
TI  - [Community structure and phylogenetic analysis of cyanobacteria in cryoconite
      from surface of the Glacier No. 1 in the Tianshan Mountains].
AB  - OBJECTIVE: The purpose of this study is to characterize the community composition
      and phylogenetic analysis of cyanobacteria from supraglacial cryoconite of the
      Glacier No. 1 in the Tianshan Mountains, China. METHODS: We amplified 16S rRNA
      genes from the extracted cryoconite DNA by PCR with 2 pairs of cyanobacteria
      specific primers. Amplificon was used to construct 16S rRNA genes clone library.
      The estimation of species richness, diversity indices, and rarefaction curve of
      the 16S rRNA genes library were determined based on representative phylotypes
      (OTUs). RESULTS: Analysis of 16S rRNA gene sequences allowed grouping of 101
      clones into 12 phylotypes (OTUs) using a cut-off of 97% identity. The
      phylogenetic analysis revealed that most of sequences affiliated to the order
      Oscillatoriales and Chroococcales except that three were unclassified. The clone
      library was dominated by representatives of the order Oscillatoriales (81% of the
      total clones), and the most abundant organisms within this order were in the
      genus Phormidium (68 clones) including clones grouping into four phylotypes. The
      only clone of Chroococcales was closely related to the genus Chamaesiphon with
      97% similarity. In addition, comparison of soil chemical properties between
      different habitats indicated that supraglacial cryoconite supported significantly
      higher the content of available phosphorus and potassium, nitrate nitrogen and
      organic matter compared with the forefield of the Glacier No. 1. CONCLUSION: The
      diversity index of cyanobacteria were relatively high in supraglacial cryoconite
      of the Glacier No. 1 in the Tianshan Mountains. The community structure was
      dominated by members of the genus Phormidium. This study may enrich our knowledge
      on biogeochemical processes and ecological distribution of cyanobacterial
      populations in glacial ecosystem.

PMID- 25752133
TI  - [Biological characteristics of an Hog1 MAPK homologous gene FoHog1 knock-out
      mutant of Fusarium oxysporum f. sp. cubense].
AB  - OBJECTIVE: This study was aimed to obtain a mitogen-activated protein kinase
      (MAPK) gene namely FoHog1 from Fusarium oxysporum f. sp. cubense and to verify
      its function. METHODS: We amplified FoHog1 gene by PCR and RT-PCR methods and
      analyzed it through bioinformatics method. PEG-mediated protoplast transformation
      was used to create the deletion mutants of FoHog1 gene. We analyzed different
      biological characteristics between knock-out strain and wild-type strain.
      RESULTS: FoHog1 gene encoding a putative protein of 357 amino acids and its
      genetic relationship with different Fusarium' s protein. Compared with the wild
      type strain, FoHog1 deletion mutants have loose hyphae colony, less spores
      production, lower dry weight of hyphae and more sensitive to temperature, pH and
      osmotic stress. FoHog1 deletion mutants also have reduced colonization ability
      compared with the wild-type strain. CONCLUSION: FoHog1 gene participated in
      mycelial growth, sporulation, catabolism of sodium acetate and ammonium chloride,
      osmotic stress response and pathogenic process with Fusarium oxysporum f. sp.
      cubense Race 4.

PMID- 25752134
TI  - [A hemerythrin-like protein MSMEG_3312 influences erythromycin resistance in
      mycobacteria].
AB  - OBJECTIVE: Reactive oxygen species are natural products of metabolism in aerobic
      organisms, which lead to oxidative damage, such as DNA mutation, protein
      inactivation and drug resistance. MSMEG_3312 was predicted as a hemerythrin-like
      protein, which can carry oxygen and reversibly bind to oxygen, thus it might play
      important roles in the process of oxygen metabolism. In this study, we explored
      the role of MSMEG_3312 in drug resistance. METHODS: On the basis of
      bioinformatics, we identified the conserved sequence of HHE domain in MSMEG_3312
      and it was predicted to have typical alpha-helix at secondary structure. To
      explore potential functions of MSMEG_3312, we constructed the msmeg_3312 knockout
      strain and compare the susceptibility to various drugs to its parent strain,
      mc2155. In addition, we also measured the promoter response when treatment of
      erythromycin. RESULTS: Genetic results showed that MSMEG_3312 is not necessary
      for M. smegmatis growth at 7H9 rich medium. The msmeg_3312 knockout strain showed
      increased erythromycin resistance. Moreover, the drug resistance is only limited
      to erythromycin which its mechanism of action is by binding to the 50S subunit of
      the bacteria ribosomal complex and then inhibit protein synthesis. However, there
      were no different MICs of other antibiotics, targets for protein synthesis
      inhibition, but not 50S subunit, such as tetracyclines, aminoglycosides and
      chloramphenicol. Moreover, we also showed that the promoter of msmeg_3312
      responses to erythromycin. CONCLUSIONS: Hemerythin-like protein MSMEG_3312 is
      involved in erythromycin resistance.

PMID- 25752135
TI  - [Secondary metabolites of the co-culture of Aspergillus sp. SCSGAF 0076 and
      Bacillus sp. MNMCCE 001].
AB  - OBJECTIVE: To elucidate the chemical structures of the main antibacterial
      compound and red pigment produced by the co-culture of marine-derived fungus
      Aspergillus sp. SCSGAF 0076 and bacterium Bacillus sp. MNMCCE 001. METHODS: The
      monoculture of strain SCSGAF 0076 and co-culture of strains SCSGAF 0076 and
      MNMCCE 001 were done on amylum solid medium for three days, then the crude
      extracts of the cultures were obtained, and subsequently, the chemical profiles
      of the extracts of monoculture and co-culture were analyzed by HPLC. Using
      antibacterial bioassay-guided fractionation, we isolated the crude extract of the
      co-culture by silica gel column chromatogram, Sephadex LH-20, and semi
      preparative HPLC to obtain the main antibacterial compound and red pigment. The
      compounds' structures were determined by spectroscopic analysis. RESULTS: We
      found that the main secondary metabolites produced by the monoculture of strain
      SCSGAF 0076 and co-culture of strains SCSGAF 0076 and MNMCCE 001 were almost the
      same, however, the contents of the main antibacterial compound and red pigment
      were obviously different. Totally, four compounds including the antibacterial
      compound penicillic acid, 5 (6) -dihydropenicillic acid, 9-chloro-8-hydroxy-8,9
      deoxyasperlactone and red pigment viopurpurin were isolated from the crude
      extract of the co-culture medium. CONCLUSION: The main antibacterial compound of
      the co-culture of strains SCSGAF 0076 and MNMCCE 001 was penicillic acid, the
      main red pigment was viopurpurin, and the yields of the two compounds were proved
      by the co-culture.

PMID- 25752136
TI  - [Function of a calcium-dependent protein kinase gene Pscamk in Puccinia
      striiformis f. sp. tritici].
AB  - OBJECTIVE: To clone calcium-dependent protein kinase gene (camk) from Puccinia
      striiformis f. sp. tritici (Pst) and analyze its function. METHODS: The cDNA full
      length of Pscamk was isolated by using reverse transcriptional-PCR (RT-PCR), and
      gene expression profile at different morphological stages was analyzed via
      quantitative real-time--PCR (qRT-PCR). Pst urediospores were treated with CaMK
      suppressor KN-93 and germination rate was investigated. RESULTS: A gene cDNA full
      length with 1 620 bp was obtained and designated as Pscamk. qRT-PCR analysis
      showed Pscamk expression was highly induced in the early stages of Pst infection
      and reached the maximum at 6 h post inoculation (hpi) as 20.74-fold as that in
      the control (0 hpi). With increasing of the concentration of CaMK suppressor KN
      93, germination rate of Pst urediospores was gradually decreased. The germination
      rate was reduced to 8.02%, only 12% of the control, under 1.4 MUmol/L KN-93
      treatment at 10 h after incubation at 9 degrees C. CONCLUSION: Pscamk might play
      a role in germination and germ tube elongation of Pst urediospores. This study
      provides a basis for exploring pathogenesis of calcium signaling pathway during
      Pst infection.

PMID- 25752137
TI  - [Effect of AUR1 gene intron on the expression of inositol phosphorylceramide
      synthase and pathogenicity in Botrytis cinerea].
AB  - OBJECTIVE: AUR1 encoding inositol phosphorylceramide (IPC) synthase is the key
      enzyme for the sphingolipid metabolism in fungi. In this study, we explored the
      mechanism of AUR1 intron on the regulation of AUR1 gene expression at
      transcriptional and translational levels in Botrytis cinerea, as well as the
      influence of AUR1 intron on the pathogenicity. METHODS: AUR1 mRNA expression of
      wild-type B. cinerea (BcAUR1) and the mutant with deletion of 115 bp intron
      (BcAUR1a) was detected by Real-time quantitative PCR. The activity of IPC
      synthase from BcAUR1 and BcAUR1 was measured through high-efficiency liquid
      fluorescent chromatogram. In addition, H2O2 concentration and activities of
      superoxide dismutase (SOD), peroxidase (POD) and catalase (CAT) per unit fungus
      were determined by horseradish peroxidase, pyrogallol oxidation, guaiacol and
      ultraviolet spectrophotometric, respectively. RESULTS: IPC synthase had no amino
      acid mutation in mutant BcAUR1a. The expression of AUR1 gene at mRNA level and
      the activity of IPC synthase in BcAUR1a increased by 50.2% and 14. 16% compared
      to those in BcAUR1. The secretion of H2O2, SOD, POD and CAT in BcAUR1 was
      significantly stimulated by Aureobasidin A (AbA) treatment, in contrast, no
      significant influence was detected upon the secretion of these substances in
      BcAUR1a via AbA treatment. CONCLUSION: The expression of AUR1 in BcAUR1a is
      significantly up-regulated at transcriptional and translational levels. AbA
      treatment can significantly enhance the pathogenicity of BcAUR1, but has a minor
      influence on the BcAUR1a. BcAUR1a is AbA-resistant. The results suggest that AUR1
      gene intron regulate the expression of AUR1 as a transcriptional repressor.

PMID- 25752138
TI  - [Restoration of microbial ammonia oxidizers in air-dried forest soils upon
      wetting].
AB  - OBJECTIVE: This study was aimed to investigate the abundance and community shift
      of ammonia-oxidizing archaea (AOA) and bacteria (AOB) in air-dried forest soils
      in response to water addition, to explore the applicability of air-dried soil for
      microbial ecology study, and to elucidate whether AOA within the marine group 1.
      1a dominate ammonia oxidizers communities in the acidic forest soils in China.
      METHODS: Soil samples were collected from 10 forest sites of the China Ecosystem
      Research Network (CERN) and kept under air-drying conditions in 2010. In 2013 the
      air-dried soil samples were adjusted to 60% of soil maximum water holding
      capacity for a 28-day incubation at 28 degrees C in darkness. DGGE
      fingerprinting, clone library construction, pyrosequencing and quantitative PCR
      of amoA genes were performed to assess community change of ammonia oxidizers in
      air-dried and re-wetted soils. RESULTS: After incubation for 28 days, the
      abundance of bacteria and archaea increased significantly, up to 3,230 and 568
      times, respectively. AOA increased significantly in 8 samples, and AOB increased
      significantly in 5 of 10 samples. However, pyrosequencing of amoA genes reveals
      insignificant changes in composition of AOA and AOB communities. Phylogenetic
      analysis of amoA genes indicates that archaeal ammonia oxidizers were
      predominated by AOA within the soil group 1. 1b lineage, while the Nitrosospira
      like AOB dominate bacteria ammonia oxidizer communities. There was a
      significantly positive correlation between AOA/AOB ratio and total nitrogen (r2 =
      0.54, P < 0.05), implying that soil ammonia oxidation might be dominated by AOA
      in association with ammonium released from soil mineralization. CONCLUSION:
      Phylogenetic analysis suggest that AOA members within the soil group 1. 1b
      lineage were not restricted to non-acidic soils as previously thought. The
      abundance rather than composition of AOA and AOB changed in response to water
      addition. This indicates that air-dried soil could be of help for microbial
      biogeography study.

PMID- 25752139
TI  - [Isolation, identification and naringin biotransforming properties of naringinase
      producing bacteria isolated from human intestinal microflora].
AB  - OBJECTIVE: Isolation of specific bacteria from human intestinal microflora to
      convert naringin to naringenin efficiently. METHODS: Fresh human feces from
      healthy individual was cultured in an anaerobic chamber for 24 h before being
      diluted and spread on agar medium. We cultured and incubated each single colony
      with the substrate naringin. The biotransformation of naringin by each single
      colony was detected by high-performance liquid chromatography (HPLC). We
      identified the isolated bacteria based on the analyses of 16S rDNA sequence and
      biochemical traits. We also studied the bioconversion kinetics of the bacteria.
      RESULTS: Four bacterial strains, named AUH-JLD3, AUH-JLD7, AUH-JLD104 and AUH
      JLD109, capable of biotransforming naringin to naringenin, were isolated and
      identified as Blautia sp. AUH-JLD3, Enterococcus sp. AUH-JLD7, Bacteroides sp.
      AUH-JLD104 and Streptococcus pasteurianus subsp. AUH-JLD109 respectively based on
      the 16S rDNA sequence analysis, bacterial cell morphology, and biochemical
      traits. Study on biotransforming kinetics showed that all the four isolated
      bacterial strains were able to convert naringin (0.2 mmol/L) to naringenin within
      12 h. The maximal concentration of the substrate naringin that strain AUH-JLD3,
      strain AUH-JLD7, strain AUH-JLD104 and strain AUH-JLD109 could biotransform
      efficiently were 0. 2 mmol/L (the average biotransforming rate was 66. 67%), 0.8
      mmol/L (the average biotransforming rate was 86.49%), 0. 2 mmol/L (the average
      biotransforming rate was 73.68%) and 1.6 mmol/L (the average biotransforming rate
      was 93.20%), respectively. CONCLUSION: The four bacterial strains were capable of
      biotransforming naringin to naringenin, among which Streptococcus pasteurianus
      subsp. AUH-JLD109 has the highest naringin biotransforming capacity.

PMID- 25752140
TI  - [Screening, identification of P-dissolving fungus P83 strain and its effects on
      phosphate solubilization and plant growth promotion].
AB  - OBJECTIVE: To isolate phosphate-solubilizing microorganisms from farmland, and to
      provide P-solubilizing microbial resource for bio-fertilizer production. METHODS:
      Phosphate-solubilizing fungus was identified using morphological and cultural
      characteristics and ITS rDNA sequence analysis. The phosphate-solubilizing
      capacity of strain P83 was measured by Petri dishes, broth medium and soil pot
      experiment. The effect of strain P83 on plant growth was studied in field trials.
      RESULTS: Strain P83 was identified as Penicillium decumbens with a strong ability
      to dissolve insoluble phosphates. P83 dissolved 42.68% Ca3 (PO4) 2 (5 g/L) and
      the concentration of available phosphorus was 956 mg/L during a 10-d shaking
      incubation. The concentration of available phosphorus dissolved from Yonghe rock
      phosphate by P83 was 152.8 mg/L after 10d shaking incubation at 28 degrees C and
      a speed of 180r/min. P. decumbens P83 had a significant growth promotion effect
      on corn in Chao soil under three phosphates such as Ca3 (PO4) 2, Zn3 (PO4) 2 and
      rock phosphate. Compared with the control, inoculation with P83 increased the
      fresh weight of corn biomass by 9.5% - 89.2% and dry weight of corn biomass by
      35% - 231%, and soil available phosphorus content increased 2.1 mg/kg -40.5 mg/
      kg. Field trials show that P. decumbens P83 had a greater effect on enhancement
      of corn grain yield, the yield was average 9.2t/hm2 and 35.3% higher than the
      control. CONCLUSION: One new phosphate- solubilizing strain P83 was obtained and
      identified as P. decumbens. It solubilized insoluble phosphates in petri dishes,
      broth medium and pot experiments. P. decumbens P83 could increase corn yield
      significantly in field trials. P. decumbens P83 strain has the potential for
      biofertilizer production in the future.

PMID- 25752141
TI  - [Intestinal fungal diversity of sub-adult giant panda].
AB  - OBJECTIVE: The fungi diversity in the guts of five sub-adult giant pandas was
      analyzed. METHOD: We analyzed the fungal internal transcribed spacer sequences
      (ITS) using restriction fragment length polymorphism (RFLP). ITS regions were
      amplified with fungal universal primers to construct ITS clone libraries. The
      fingerprints were analyzed by restriction fragment length polymorphism using the
      Hha I and Hae III enzymes. The cloned PCR products were analyzed by sequencing
      and diversities were demonstrated by phylogenetic tree. RESULTS: The gut fungi of
      5 sub-adult giant pandas were mainly composed of Ascomycota (average of 46.24%),
      Basidiomycota ( average of 15.79%), unclassified (average of 29.14%), uncultured
      fungus (average of 8.83% ). Ascomycota was mainly composed of Saccharomycetes
      (average of 63.74%) and Dothideomycetes ( average of 35.91%); Basidiomycota was
      mainly composed of Tremellomycetes (average of 65.80%) and Microbotryomycetes
      (average of 33.15%). Four classes were mainly composed of Candida and
      Debaryomyces; Pleosporales and Myriangium; Cystofilobasidium and Trichosporon;
      Leucosporidium, and Leucosporidiella, whereas the proportions were different for
      each sample. CONCLUSION: Fungal flora existing in the intestines of sub-adult
      giant pandas expand our knowledge on the structure of the giant panda gut
      microbes and also help us to further study whether fungal flora can help giant
      pandas digest high-fiber foods.

PMID- 25752142
TI  - [Comparison of immunoprotection between vaccination with meq-deleted Marek's
      disease virus and vaccine strain CVI988/Rispens].
AB  - OBJECTIVE: To evaluate and compare the immunoprotection between a meq-deleted
      Marek's disease virus (MDV) and CVI988/Rispens against MDV very virulent strain
      GX0101. METHODS: In total 120 one-day-old SPF chickens were divided into 4 groups
      (30 each) and kept in 5 isolators with positive pressure-filtered air. At 1 day
      of age, 2000 PFU of SC9-1 was inoculated subcutaneously into each bird in group
      1; 2000 PFU of commercial vaccine CVI988/ Rispens was inoculated subcutaneously
      into each bird in group 2. No viral challenge was made in group 3 and 4 as
      controls. Five days later chickens in group 1, 2, 3 were challenged intra
      abdominally with 2000 PFU of very virulent MDV strain GX0101. During 90 days
      after challenge, all dead birds were recorded and checked for necropsy. The tumor
      suspected tissues were examined by histopathological biopsy. The antibody titers
      induced by AIV and NDV vaccination and propagation dynamics of MDV GX0101 were
      detected. At the same time, parallel tests were performed on Hy-Line Brown
      chickens containing MDV maternal antibody. RESULTS: SC9-1 stain provided 100%
      protective efficiency against very virulent GX0101 challenge in SPF and Hy-Line
      Brown chickens. CVI988/Rispens provided 86. 7% protective efficiency against very
      virulent GX0101 challenge in SPF chickens and 93% in Hy-Line Brown chickens.
      Challenge with GX0101 caused 53.3% mortality and 16.7% of birds with gross tumors
      in SPF chickens while there was 36.7% mortality and 16.7% of birds with gross
      tumors in Hy-Line Brown chickens, and there was no tumor lesion in
      histopathological biopsy in control group. The results of qPCR demonstrated that
      the copies of GX0101 viral genomes in SC9-1 vaccinated chickens was lower than
      CVI988/Rispens vaccinated chickens in lymphocyte and feather follicle DNA. The
      results of hemagglutination inhibition test demonstrated that antibody titers of
      AIV and NDV was higher in SC9-1 vaccinated chickens than that in CVI988/Rispens
      vaccinated chickens. CONCLUSION: SC9-1 stain's immunoprotection against MDV is
      more effective than CVI988/Rispens strain's both in SPF chickens and commercial
      Hy-Line Brown chickens containing maternal antibody.

PMID- 25752143
TI  - [Clustered regularly interspaced short palindromic repeats (CRISPR) site in
      Bacillus anthracis].
AB  - OBJECTIVE: To investigate the polymorphism of clustered regularly interspaced
      short palindromic repeats (CRISPR) in Bacillu santhracis and the application to
      molecular typing based on the polymorphism of CRISPR in B. anthracis. METHODS: We
      downloaded the whole genome sequence of 6 B. anthracis strains and extracted the
      CRISPR sites. We designed the primers of CRISPR sites and amplified the CRISPR
      fragments in 193 B. anthracis strains by PCR and sequenced these fragments. In
      order to reveal the polymorphism of CRISPR in B. anthracis, wealigned all the
      extracted sequences and sequenced results by local blasting. At the same time, we
      also analyzed the CRISPR sites in B. cereus and B. thuringiensis. RESULTS: We did
      not find any polymorphism of CRISPR in B. anthracis. CONCLUSION: The molecular
      typing approach based on CRISPR polymorphism is not suitable for B. anthracis,
      but it is possible for us to distinguish B. anthracis from B. cereus and B.
      thuringiensis.

PMID- 25752144
TI  - [Degradation of fatty acid by syntrophic hydrocarbon-degrading consortium M82].
AB  - OBJECTIVE: Using molecular ecology methods, we screened non-hydrocarbon carbon
      sources suitable for growth of syntrophic hydrocarbon-degrading Syntrophus sp.
      METHODS: The acclimated methanogenic hexadecane-degrading consortium M82 was
      subcultured with dodecanedioic acid, tetradecanedioic acid, hexadecanoic acid,
      propionate and lactate. PCR-DGGE and qPCR were used to analyze the abundance and
      quantity of syntrophaceae using different carbon sources. The T-RFLP was applied
      to analyze archaeal community. RESULTS: The consortium M82 could grow and produce
      methane using a variety of fatty acids that also resulted in the change in
      bacterial microbial community structure. Syntrophaceae bacterial stripe was
      obviously detected in the culture added additional dodecanedioic acid and
      tetradecanedioic acid. Furthermore, the results show that the logarithmic
      abundance of Syntrophaceae was 7.4 and 7.6 in per milliliter culture in the two
      enrichment cultures respectively, which were 2 - 3 units higher than these in
      other cultures. The archaeal community structure was mainly composed of
      acetoclastic methanogens Methanosaeta and hydrogenotrophic methanogens
      Methanoculleus in all culture. CONCLUSION: Syntrophus sp. can use non-hydrocarbon
      carbon source (dodecanedioic acid and tetradecanedioic acid) as substrate to
      grow, which provides valuable information to isolate syntrophic hydrocarbon
      bacteria, and reveal the molecular mechanism of syntrophic hydrocarbon
      degradation.

PMID- 25752145
TI  - [Biological characteristics and histopathological observation of Vibrio
      alginolyticus from diseased fish].
AB  - OBJECTIVE: Ulcer disease is one of the most serious diseases and a common problem
      in various stages marine culture including Epinephelus coioides culture of
      southern China. The isolation and identification of pathogenic bacteria from E.
      coioides will be useful for monitoring of drug resistance and controlling the
      outbreak and spread of ulcer disease in E. coioides. The purpose of this study
      was to characterize the pathogen of E. coioides. METHODS: The pathogenic bacteria
      separated from the liver and kidney of diseased fish were identified through pure
      culture, artificial infection, automatic tests in bacteriology automatic
      identification, drug sensitive tests, morphometry, and physiological and
      biochemical determination. RESULTS: The strains were characterized and identified
      as Vibrio alginolyticus. Two strain were selected for virulence tests and all the
      moribund/dead fish exhibited ulcer disease as that observed in natural outbreak.
      Drug sensitive tests show that V. alginolyticus was highly resistant to 3 agents
      including penicillin, whereas sensitive to 5 agents including chloromycetin.
      Histopathological changes were mainly shown as cell degeneration and necrosis of
      gill, liver and kidney, and alterative inflammation as a result of inflammatory
      cell infiltration in the diseased tissue. CONCLUSION: The biochemical,
      physiological tests confirm that V. alginolyticus is the pathogen causing E.
      coioides vibriosis. The multi-drug resistance among V. alginolyticus suggests
      strengthened monitoring of outbreaks of V. alginolyticus caused disease in E.
      coioides culture.

PMID- 25752146
TI  - [Age-related changes in the rat lacrimal gland: specific morphology and unknown
      nature].
AB  - The rat lacrimal apparatus includes several glands; among them, the exorbital
      gland plays the central role. Its parenchyma and stroma undergo prominent
      morphologic changes with age. The parenchymal transformation includes metaplasia
      of some of its acini and their turning into Harderian gland-like structures
      (harderization), accumulation of gland ducts ("ductularization"), and morphologic
      dysplasia-cytomegaly, karyomegaly, and'cell and nuclearpolymorphism in the other
      part of acini. All these transformations are hormone-dependent andsex-specific:
      theyoften appear in males. On the final stages of age-related transformations,
      the lacrimal gland tissue is morphologically similar to the neoplasm and has
      neoplastic morphology but no other features of a tumor. Therefore, the rat
      lacrimal gland is an interesting object to study tissue and cell atypia. In the
      rat glandular stroma, lymphocytic infiltration and fibrosis appear with age;
      these changes are similar to processes taking place in human lacrimal apparatus
      involved in the pathogenesis of senile dry eye syndrome. The spontaneous changes
      in the rat lacrimal gland, predominantly in male rats, can be used as a model of
      the human lacrimal apparatus disorders.

PMID- 25752147
TI  - [Assisted reproductive technologies and arterial hypertension].
AB  - The effects of assisted reproductive technologies on the development of
      hypertensive phenotype were reviewed. A special emphasis is made on the effects
      of embryo culture and subsequent transfer on the blood pressure in the offspring.
      The analysis of studies with the laboratory models, mostly hypertensive strains
      of rats, is performed. These data are discussed in the context of the use
      theassisted reproductive technologies in medicine.

PMID- 25752148
TI  - [Regeneration and fibrosis of corneal tissues].
AB  - In this review, the features of the regeneration of corneal tissue and its
      disorders leading to the development of fibrosis are considered. The data on the
      presence of stem (clonogenic) cell pool in the corneal tissues (epithelium,
      endothelium, stroma) are given; these cells can serve as a source for
      regeneration of the tissues at injury or various diseases. The main steps of
      regeneration of corneal tissues and their disorders that lead to outstripping
      proliferation of myofibroblasts and secretion of extracellular matrix in the
      wound area and eventually cause the formation of connective tissue scar and
      corneal opacity are considered. Particular attention is given to the successes of
      translational medicine in the treatment of corneal tissue fibrosis. The methods
      of cell therapy aimed at the restoration of stem cell pool of corneal tissues are
      the most promising. Gene therapy provides more opportunities; one of its main
      objectives is the suppression of the myofibroblast proliferation responsible for
      the development of fibrosis.

PMID- 25752149
TI  - [The gene NANA regulates cell proliferation in Arabidopsis thaliana shoot apical
      meristem without interaction with CLV1, CLV2, CLV3].
AB  - A constancycy of stem cell pool in shoot apical meristem of Arabidopsis thaliana
      is provided by a genetic regulation system with negative feedback loop based on
      the interaction of the gene WUS, which maintains indeterminate state of cells,
      with CLV genes, which restrict the level of WUS expression and stem cell pool
      size. clv mutations lead to an increase in the pool of stem cells in the apical
      and floral meristems and wus mutation leads to the opposite effect. Mutation na
      (nana), like wus mutation, causes premature termination of shoot apical meristem
      function, although it does not affect the activity of the flower meristem. To
      elucidate the role of NA in the control of shoot apical meristem functioning, the
      interaction of NA with CLVgenes were investigated. Additive phenotype of double
      mutants na clv1, na clv1-1, anl na clv3-2 indicates that the NA gene makes an
      independent contribution to the functioning of the shoot apical meristem. It is
      assumed that the NA gene controls apical meristem cell proliferation during the
      transition to the reproductive phase of plant development, acting much later and
      independently of the genes WUS-CLV.

PMID- 25752150
TI  - [The tissue oxygen partial pressure in organs of hens in the second half of
      embryogenesis and in the first days after hatching].
AB  - The aim of the study was measure the development chick tissue partial pressure of
      oxygen (pO2) in the brain cerebral hemispheres, liver, M. pectoralis, M.
      gastrocnemius, and to estimate the correlation of this index with our previously
      measured values (laser-Doppler flowmetry) volume blood flow (BF) in these organs.
      We studied 10-, 15-, and 19-day embryos and 4-day chickens thatwere anesthetized
      with urethane. pO2 measurements were made in thesurface layers of organs by the
      membrane amperometric Clark-type O2-electrode with a diameter of about 50 microm
      of the cathode placed in the center of the sensor with an outer diameter of 3.4
      mm. Disclosed noticeable distinction of both the organ tissue pO2 values, and the
      dynamics of their changes duringthe study period. The most important of them: (1)
      the lowest pO2 (and BF) is observed in the brain and particularly in the liver of
      10-day embryos; (2) in the subsequent period of embryogenesis pO2 in the brain
      increases 1.9 times (rising and BF) in M. pectoralis it falls by 1.7 times and in
      the liver.and in M. gastrocnemius changes little wherein the BF in both liver and
      muscles is not changed, (3) after hatching pO2 in the liver and M. petoralis fold
      increased (also increasing and BF), and in the brain and M. gastrocnemius,
      despite the increase BF (greater in the niuscle) did not significant change. In
      the analysis ofthedata are considered two possible mechanisms of change of tissue
      pO2 in the developing organs of chickens, one is due to the peculiarities of
      intracardiac blood flows; and the other is related to thesingularity of the
      oxyhemoglobin dissociation in the blood capillary bed of organ, determined by the
      specifics of its oxidative metabolism.

PMID- 25752151
TI  - [Reproductive strategy of the alien fishhook waterflea Cercopagis pengoi
      (Ostroumov, 1891) in the Baltic Sea (by example of the Vistula Lagoon)].
AB  - Early and prolonged bisexual reproduction has been registered in the population
      of Cercopagis pengoi within the Vistula Lagoon relative to its original habitat.
      Decrease in the role of parthenogenesis and increase in the frequency of
      gamogenesis have been registered in the population under study. It has been
      accompanied by reduction in the average number of parthenogenetic eggs per female
      and increase in the production ofgamogenetic eggs relative to the Caspian Sea.

PMID- 25752152
TI  - [Morphological changes in ventricular germinal zone and neocortex of the cerebral
      hemispheres in human fetuses and newborns on weeks 22-40 of prenatal
      development].
AB  - In this study, we investigated the morphology of the ventricular germinal zone
      and neocortex of the cerebral hemispheres in the projection field no. 4 of the
      motor area in human fetuses in dynamics from week 22 to 40 of fetal development.
      Morphological study allowed us to clarify the following patterns of prenatal
      ontogeny of the human CNS. On weeks 22-27, an intensive formation of the main
      sulci of the first order, differentiating the brain into lobes, is observed. By
      weeks 28-32, the formation of all sulci of the first order is completed; and on
      weeks 33-37, additional sulci characteristic of an individual are formed. The
      spurt of gyrification of the cortex (weeks 22-27) practically coincides with the
      completion of neuronal differentiation and formation of the motor neocortex. The
      structure of the latter is characterized by a clear stratification of
      cytoarchitectonic layers and modular organization of neurons with their vertical
      orientation in cell columns (weeks 25-27). In subsequent weeks of prenatal
      development until birth, no significant changes in the topography and structure
      of the neocortex are observed. Structural rearrangement of the ventricular
      germinal zone on weeks 22-40 of prenatal development consists in its gradual
      reduction and is completed on weeks 37-40. The criteria of physiological
      reduction of this area are the zonal location of glioblasts and a progressive
      decrease in its thickness on weeks 33-37 of prenatal development.

PMID- 25752154
TI  - Urban health post-2015.

PMID- 25752153
TI  - [Study of possible involvement of MEK mitogen-activated protein kinase and TGF
      beta receptor in planarian regeneration processes using pharmacological
      inhibition analysis].
AB  - Possible involvement of MEK mitogen-activated protein kinase and TGF-beta
      receptor in the processes of regeneration and morphogenesis in freshwater
      planarian flatworms Schmidtea mediterranea was studied using a pharmacological
      inhibitor analysis. It was found that pharmacological inhibitors of these kinases
      significantly inhibit the regeneration of the head end of the animals and that
      this effect is realized due to inhibition of proliferative activity of neoblasts,
      planarian stem cells. It is shown that that the inhibition of the studied protein
      kinases in regenerating planarians markedly disturbs stem cell differentiation
      and morphogenesis.

PMID- 25752155
TI  - Antimicrobial espionage?

PMID- 25752156
TI  - Reducing the cost of rare disease drugs.

PMID- 25752157
TI  - The future of mental health in the UK: an election manifesto.

PMID- 25752158
TI  - 2018 FIFA World Cup: isolating Russia could harm global health.

PMID- 25752159
TI  - Rare diseases and effective treatments: are we delivering?

PMID- 25752162
TI  - US FDA: the Margaret Hamburg years.

PMID- 25752163
TI  - Greek Government plans health system overhaul.

PMID- 25752165
TI  - Robert Califf: leading cardiologist is new FDA Deputy Commissioner.

PMID- 25752166
TI  - The library card.

PMID- 25752167
TI  - Mary Frances Lyon.

PMID- 25752168
TI  - Putting health first in universal health coverage.

PMID- 25752169
TI  - Urban health in the post-2015 agenda.

PMID- 25752170
TI  - Alemtuzumab induction therapy in kidney transplantation.

PMID- 25752171
TI  - Alemtuzumab induction therapy in kidney transplantation.

PMID- 25752172
TI  - Post-partum depressive episodes and bipolar disorder.

PMID- 25752173
TI  - Alemtuzumab induction therapy in kidney transplantation - Authors' reply.

PMID- 25752174
TI  - Raising awareness against acid attacks.

PMID- 25752175
TI  - Guidelines on cervical and breast cancer screening in Greece.

PMID- 25752176
TI  - Prevalence of tuberculosis in China.

PMID- 25752177
TI  - Antibiotic pollution threatens public health in China.

PMID- 25752180
TI  - Melatonin, the new partner to aspirin?

PMID- 25752181
TI  - A public health approach to global management of hypertension.

PMID- 25752182
TI  - Seizures and metrorrhagia: a case of denied pregnancy.

PMID- 25752184
TI  - Trading health for oil? Uganda should not export its health workers.

PMID- 25752187
TI  - Lipoxygenase-derived 9-hydro(pero)xides of linoleoylethanolamide interact with
      ABA signaling to arrest root development during Arabidopsis seedling
      establishment.
AB  - Ethanolamide-conjugated fatty acid derivatives, also known as N-acylethanolamines
      (NAEs), occur at low levels (MUg per g) in desiccated seeds, and endogenous
      amounts decline rapidly with seedling growth. Linoleoylethanolamide (NAE18:2) is
      the most abundant of these NAEs in seeds of almost all plants, including
      Arabidopsis thaliana. In Arabidopsis, NAE18:2 may be oxidized by lipoxygenase
      (LOX) or hydrolyzed by fatty acid amide hydrolase (FAAH) during normal seedling
      establishment, and this contributes to the normal progression of NAE depletion
      that is coincident with the depletion of abscisic acid (ABA). Here we provide
      biochemical, genetic and pharmacological evidence that a specific 9-LOX
      metabolite of NAE18:2 [9-hydro(pero)xy linoleoylethanolamide (9-NAE-H(P)OD)] has
      a potent negative influence on seedling root elongation, and acts synergistically
      with ABA to modulate the transition from embryo to seedling growth. Genetic
      analyses using mutants in ABA synthesis (aba1 and aba2), perception (pyr1, pyl1,
      pyl2, pyl4, pyl5 and pyl8) or transcriptional activation (abi3-1) indicated that
      arrest of root growth by 9-NAE-H(P)OD requires an intact ABA signaling pathway,
      and probably operates to increase ABA synthesis as part of a positive feedback
      loop to modulate seedling establishment in response to adverse environmental
      conditions. These results identify a specific, bioactive ethanolamide oxylipin
      metabolite of NAE18:2, different from those of ethanolamide-conjugated linolenic
      acid (NAE18:3), as well as a molecular explanation for its inhibitory action,
      emphasizing the oxidative metabolism of NAEs as an important feature of seedling
      development. 

PMID- 25752188
TI  - Thermal stability of cytochrome c' from mesophilic Shewanella amazonensis.
AB  - Cytochrome c' (SACP) from mesophilic Shewanella amazonensis, growing optimally at
      37  degrees C, was thermally more stable than cytochrome c' (AVCP) from
      mesophilic Allochromatium vinosum, growing optimally at 25  degrees C. In
      contrast, SACP was less stable than cytochrome c' (PHCP) from thermophilic
      Hydrogenophilus thermoluteolus, growing optimally at 52  degrees C. Although only
      28% of the SACP amino acid sequence was identical to those of AVCP and PHCP, the
      latter two being 55% identical, the overall main chain structures of the three
      cytochromes c' were similar, and SACP exhibited thermal stability intermediate
      between those of AVCP and PHCP. For these three proteins, the higher the
      stability is, the lesser the number of Gly residues in the putative alpha-helical
      regions is. Cytochromes c' including the present three are suitable for examining
      the protein stabilization mechanisms, because they are structurally similar and
      available from environments with a wide range of temperatures.

PMID- 25752189
TI  - Combined medico-surgical strategy for invasive sino-orbito-cerebral breakthrough
      fungal infection with Hormographiella aspergillata in an acute leukaemia patient.
AB  - Hormographiella aspergillata is a rare causative agent of invasive filamentous
      breakthrough infection, mostly arising after echinocandin exposure. We report a
      neutropenic patient who developed a severe sino-orbito-cerebral H. aspergillata
      infection while receiving empirical caspofungin, successfully controlled by an
      aggressive strategy associating surgical debridement and combined high-dose
      regimen of antifungal drugs. 

PMID- 25752190
TI  - Cutaneous manifestations of peripheral T-cell lymphoma, not otherwise specified:
      a case series highlighting the diagnostic challenges for this heterogeneous
      group.
AB  - Peripheral T-cell lymphoma, not otherwise specified (PTCL, NOS) is a rare,
      heterogeneous group of nodal and extranodal mature T-cell lymphomas that do not
      correspond to any of the defined T-cell entities, according to the World Health
      Organization classification. Most cases present with late stage nodal disease;
      however extranodal involvement is common. Skin and subcutaneous involvement is
      reported in approximately 20% of cases. Little attention has been given to the
      highly variable skin manifestations in the literature. It is our experience that
      lesions can present in ways other than previously described nodular or tumourous
      lesions that often ulcerate. We present a case series from a large tertiary
      institution of seven cases of PTCL, NOS with skin involvement, highlighting the
      variable presentations and diagnostic challenges for this heterogeneous group. 

PMID- 25752191
TI  - Prevalence and molecular defect characterization of glucose-6-phosphate
      dehydrogenase deficiency in Brazilian blood donors.

PMID- 25752192
TI  - Practical cut-offs for visual rating scales of medial temporal, frontal and
      posterior atrophy in Alzheimer's disease and mild cognitive impairment.
AB  - BACKGROUND: Atrophy in the medial temporal lobe, frontal lobe and posterior
      cortex can be measured with visual rating scales such as the medial temporal
      atrophy (MTA), global cortical atrophy - frontal subscale (GCA-F) and posterior
      atrophy (PA) scales, respectively. However, practical cut-offs are urgently
      needed, especially now that different presentations of Alzheimer's disease (AD)
      are included in the revised diagnostic criteria. AIMS: The aim of this study was
      to generate a list of practical cut-offs for the MTA, GCA-F and PA scales, for
      both diagnosis of AD and determining prognosis in mild cognitive impairment
      (MCI), and to evaluate the influence of key demographic and clinical factors on
      these cut-offs. METHODS: AddNeuroMed and ADNI cohorts were combined giving a
      total of 1147 participants (322 patients with AD, 480 patients with MCI and 345
      control subjects). The MTA, GCA-F and PA scales were applied and a broad range of
      cut-offs was evaluated. RESULTS: The MTA scale showed better diagnostic and
      predictive performances than the GCA-F and PA scales. Age, apolipoprotein E
      (ApoE) epsilon4 status and age at disease onset influenced all three scales. For
      the age ranges 45-64, 65-74, 75-84 and 85-94 years, the following cut-offs should
      be used. MTA: >=1.5, >=1.5, >=2 and >=2.5; GCA-F, >=1, >=1, >=1 and >=1; and PA,
      >=1, >=1, >=1 and >=1, respectively, with an adjustment for early-onset ApoE
      epsilon4 noncarrier AD patients (MTA: >=2, >=2, >=3 and >=3; and GCA-F: >=1, >=1,
      >=2 and >=2, respectively). CONCLUSIONS: If successfully validated in clinical
      settings, the list of practical cut-offs proposed here might be useful in
      clinical practice. Their use might also (i) promote research on atrophy subtypes,
      (ii) increase the understanding of different presentations of AD, (iii) improve
      diagnosis and prognosis and (iv) aid population selection and enrichment for
      clinical trials.

PMID- 25752193
TI  - Selected ginsenosides of the protopanaxdiol series are novel positive allosteric
      modulators of P2X7 receptors.
AB  - BACKGROUND AND PURPOSE: The P2X7 receptor is an ATP-gated ion channel
      predominantly expressed in immune cells and plays a key role in inflammatory
      processes. Ginseng is a well-known Chinese herb with both pro- and anti
      inflammatory properties and many of its actions have been ascribed to constituent
      ginsenosides. We screened a number of ginsenoside compounds for pharmacological
      activity at P2X7 receptors, that might contribute to the reported
      immunomodulatory actions of ginseng. EXPERIMENTAL APPROACH: We used several
      assays to measure responses of P2X7 receptors, ATP-mediated dye uptake,
      intracellular calcium measurement and whole-cell patch-clamp recordings. HEK-293
      cells stably expressing human P2X7 receptors were used in addition to mouse
      macrophages endogenously expressing P2X7 receptors. KEY RESULTS: Four
      ginsenosides of the protopanaxdiol series, Rb1, Rh2, Rd and the metabolite
      compound K (CK) potentiated the dye uptake responses of P2X7 receptors, whereas
      other ginsenosides tested were ineffective (1-10 MUM). The potentiation was rapid
      in onset, required a threshold concentration of ATP (>50 MUM) and had an EC50 of
      1.08 MUM. CK markedly enhanced ATP-activated P2X7 currents, probably via an
      extracellular site of action. One of the consequences of this potentiation effect
      is a sustained rise in intracellular Ca(2+) that could account for the decrease
      in cell viability in mouse macrophages after a combination of 500 MUM ATP and 10
      MUM CK that are non-toxic when applied alone. CONCLUSIONS AND IMPLICATIONS: This
      study identifies selected ginsenosides as novel potent allosteric modulators of
      P2X7 channels that may account for some of the reported immune modulatory actions
      of protopanaxdiol ginsenosides in vivo.

PMID- 25752194
TI  - Bridging the sanitation gap between disaster relief and development.
AB  - By interpreting disasters as opportunities to initiate the fulfilment of
      development needs, realise the vulnerability of the affected community and
      environment, and extend the legacy of relief funds and effort, this paper builds
      upon the concept linking relief, rehabilitation and development (LRRD) in the
      sanitation sector. It aims to use a composite of case studies to devise a
      framework for a semi-hypothetical scenario to identify critical components and
      generic processes for a LRRD action plan. The scenario is based on a latrine
      wetland sanitation system in a Muslim community. Several sub-frameworks are
      developed: (i) latrine design; (ii) assessment of human waste treatment; (iii)
      connective sanitation promotion strategy; and (iv) ecological systems and
      environmental services for sanitation and development. This scenario illustrates
      the complex issues involved in LRRD in sanitation work and provides technical
      notes and references for a legacy plan for disaster relief and development. 

PMID- 25752195
TI  - 4-Hexyl-1,3-phenylenediol, a nuclear factor-kappaB inhibitor, improves
      photodamaged skin and clinical signs of ageing in a double-blinded, randomized
      controlled trial.
AB  - BACKGROUND: The nuclear factor-kappaB (NF-kappaB) pathway is a key mediator of
      inflammation; however, few studies have examined the direct effects of NF-kappaB
      inhibition on the skin. OBJECTIVES: To investigate NF-kappaB activity in cultured
      human fibroblasts and to investigate the effects of 4-hexyl-1,3-phenylenediol (an
      NF-kappaB inhibitor) on elastin and collagen gene expression in vitro and on the
      clinical appearance of photodamaged skin. METHODS: The amount and activity of NF
      kappaB in human fibroblasts obtained from donors (17-78 years old) was measured
      after transfection with a NF-kappaB reporter and a luciferase promoter system.
      The expression of extracellular matrix (ECM) genes was determined using
      quantitative polymerase chain reaction. Women with moderate skin photodamage were
      randomized to daily treatment with a topical lotion containing 4-hexyl-1,3
      phenylenediol (n = 30) or vehicle (n = 29) for 8 weeks, with clinical assessments
      at baseline and weeks 2, 4 and 8. RESULTS: Fibroblasts obtained from donors older
      than 50 years had higher NF-kappaB activity compared with cells from younger
      donors; inhibition of the NF-kappaB pathway with 4-hexyl-1,3-phenylenediol
      enhanced the expression of ECM genes. In women, treatment for 8 weeks with 4
      hexyl-1,3-phenylenediol significantly improved crow's feet fine lines, cheek
      wrinkles, age spots, mottled pigmentation and radiance compared with both the
      vehicle and baseline. Furthermore, treatment with 4-hexyl-1,3-phenylenediol
      resulted in a twofold greater clinical improvement in overall photodamage
      compared with the vehicle group. CONCLUSIONS: Inhibition of the proinflammatory
      NF-kappaB pathway resulted in increased expression of ECM proteins in vitro and
      significant clinical improvement in photodamaged skin.

PMID- 25752196
TI  - HLA-C*06:103, a novel allele was identified in a Chinese patient awaiting
      hematopoietic stem cell transplantation.
AB  - HLA-C*06:103 shows four nucleotides difference from that of HLA-C*06:02:01:01. 

PMID- 25752197
TI  - Telomere fusion threshold identifies a poor prognostic subset of breast cancer
      patients.
AB  - Telomere dysfunction and fusion can drive genomic instability and clonal
      evolution in human tumours, including breast cancer. Telomere length is a
      critical determinant of telomere function and has been evaluated as a prognostic
      marker in several tumour types, but it has yet to be used in the clinical
      setting. Here we show that high-resolution telomere length analysis, together
      with a specific telomere fusion threshold, is highly prognostic for overall
      survival in a cohort of patients diagnosed with invasive ductal carcinoma of the
      breast (n = 120). The telomere fusion threshold defined a small subset of
      patients with an extremely poor clinical outcome, with a median survival of less
      than 12 months (HR = 21.4 (7.9-57.6), P < 0.0001). Furthermore, this telomere
      length threshold was independent of ER, PGR, HER2 status, NPI, or grade and was
      the dominant variable in multivariate analysis. We conclude that the fusogenic
      telomere length threshold provides a powerful, independent prognostic marker with
      clinical utility in breast cancer. Larger prospective studies are now required to
      determine the optimal way to incorporate high-resolution telomere length analysis
      into multivariate prognostic algorithms for patients diagnosed with breast
      cancer.

PMID- 25752200
TI  - No evidence of a role for cystatin B gene in juvenile myoclonic epilepsy.
AB  - Genetic factors play a major role in the etiology of juvenile myoclonic epilepsy
      (JME), a common form of idiopathic generalized epilepsy, but so far, genes
      related to JME remain largely unknown. JME shares electroclinical features with
      Unverricht-Lundborg disease (progressive myoclonic epilepsy type 1; EPM1), a form
      of progressive myoclonus epilepsy characterized by myoclonus, epilepsy, and
      gradual neurologic deterioration. EPM1 is caused by mutations in the gene that
      codes for cystatin B (CSTB), an inhibitor of cysteine protease. In the present
      study, we wished to investigate the role of the CSTB gene in patients with JME.
      Fifty-seven unrelated patients (35 women; mean age +/- standard deviation [SD],
      24.1 +/- 7.7; mean age +/- SD at onset, 15.3 +/- 2.4) with JME were enrolled.
      Twenty-three of 57 patients were the probands of families with JME. The molecular
      diagnosis was carried out to identify the common dodecamer repeat expansion
      mutation or other disease-causing mutations in the CSTB gene. The molecular
      analysis did not depict mutations in any of the 57 patients with JME. Our study
      did not support a role for the CSTB gene in patients with familial or sporadic
      JME.

PMID- 25752199
TI  - Dopamine and serotonin genetic risk scores predicting substance and nicotine use
      in attention deficit/hyperactivity disorder.
AB  - Individuals with attention deficit/hyperactivity disorder (ADHD) are at increased
      risk of developing substance use disorders (SUDs) and nicotine dependence. The co
      occurrence of ADHD and SUDs/nicotine dependence may in part be mediated by shared
      genetic liability. Several neurobiological pathways have been implicated in both
      ADHD and SUDs, including dopamine and serotonin pathways. We hypothesized that
      variations in dopamine and serotonin neurotransmission genes were involved in the
      genetic liability to develop SUDs/nicotine dependence in ADHD. The current study
      included participants with ADHD (n = 280) who were originally part of the Dutch
      International Multicenter ADHD Genetics study. Participants were aged 5-15 years
      and attending outpatient clinics at enrollment in the study. Diagnoses of ADHD,
      SUDs, nicotine dependence, age of first nicotine and substance use, and alcohol
      use severity were based on semi-structured interviews and questionnaires. Genetic
      risk scores were created for both serotonergic and dopaminergic risk genes
      previously shown to be associated with ADHD and SUDs and/or nicotine dependence.
      The serotonin genetic risk score significantly predicted alcohol use severity. No
      significant serotonin * dopamine risk score or effect of stimulant medication was
      found. The current study adds to the literature by providing insight into genetic
      underpinnings of the co-morbidity of ADHD and SUDs. While the focus of the
      literature so far has been mostly on dopamine, our study suggests that serotonin
      may also play a role in the relationship between these disorders.

PMID- 25752201
TI  - Accuracy of loop-mediated isothermal amplification for the diagnosis of
      Clostridium difficile infection: a systematic review.
AB  - Loop-mediated isothermal DNA amplification (LAMP) is currently used as standalone
      diagnostic test for C. difficile infection (CDI). We assessed the diagnostic
      accuracy of LAMP for the diagnosis of CDI. We searched 5 databases to identify
      studies that compared LAMP with culture cytotoxicity neutralization assay or
      anaerobic toxigenic culture (TC) of C. difficile. We used the random-effects
      model to calculate pooled sensitivities, specificities, diagnostic odds ratios,
      and their 95% confidence intervals (CIs). The search of the databases yielded 16
      studies (6979 samples) that met inclusion criteria. When TC was used as the gold
      standard (6572 samples), bivariate analysis yielded a mean sensitivity of 0.95
      (95% CI, 0.93-0.97; I(2)=67.4) and a mean specificity of 0.99 (95% CI, 0.96-1.00;
      I(2)=97.0). LAMP is a useful diagnostic tool with high sensitivity and
      specificity for detecting CDI. The results should, however, be interpreted only
      in the presence of clinical suspicion and symptoms of CDI. 

PMID- 25752202
TI  - Circulation of a multiresistant, conjugative, IncA/C plasmid within the
      nosocomial Providencia stuartii population in the Athens area.
AB  - The objective of the study is to report a multidrug-resistant outbreak of
      Providencia stuartii that occurred in inpatients in the Athens area in 2012
      resulting from a very successful transmissible A/C multidrug-resistant plasmid.
      Thirteen multidrug-resistant P. stuartii clinical isolates from 5 hospitals were
      studied. Molecular typing was performed by pulsed-field gel electrophoresis.
      Antibiotic resistance genes and their genetic surround were detected by PCR and
      sequencing. Plasmid analysis included conjugation experiments using liquid
      cultures, sizing by S1 digestion, and incompatibility replicon typing by PCR.
      Isolates were grouped into 2 distinct clonal types A and B, exhibiting similarity
      less than 70%. Isolates of type A were recovered from patients hospitalized in 4
      different hospitals with no obvious epidemiological linkage, while isolates of
      type B were recovered from patients treated in a single hospital. Both clonal
      types harbored a conjugative plasmid of 130 bp and IncA/C replicon type carrying
      5 beta-lactamase genes bla(SHV-5), bla(VEB-1), bla(VIM-1), bla(OXA-10), and
      bla(TEM-1) and aminoglycosides resistant determinants. All beta-lactamase genes
      were included in stable structures as IS26, IS1999, and In-e541. The current
      plasmid seemed to have many common determinants with previously reported plasmids
      derived from P. stuartii and Proteus mirabilis clinical isolates and exhibited
      the ability to circulate in nosocomial bacterial populations.

PMID- 25752204
TI  - Preparation of an engineered safer immunotoxin against colon carcinoma based on
      the ribotoxin hirsutellin A.
AB  - Immunotoxins are chimeric proteins composed of an antibody domain that
      specifically directs the action of the toxic domain, resulting in the death of
      the targeted cells. Over recent years, immunotoxins have been widely studied and
      the number of different constructions has increased exponentially. Protein
      engineering has allowed the design of optimized versions of immunotoxins with an
      improved tumor binding affinity, stability or cytotoxic efficacy, although
      sometimes this has compromised the safety of the patient in terms of undesirable
      adverse secondary reactions. A triple mutant at three Trp residues (HtA3DeltaW)
      of the ribotoxin hirsutellin A retains its specific ribonucleolytic activity,
      although cell internalization capacity is lacking. This toxin variant has been
      fused to the single chain variable fragment A33 (scFvA33). This immunoconjugate
      (IMTXA33HtA3DeltaW) was produced in the methylotrophic yeast Pichia pastoris and
      purified using nickel-nitrilotriacetic acid affinity chromatography. Both target
      and toxic domains were characterized. The immunotoxin showed an exquisite
      specific binding against GPA33-positive culture cells, which results in the death
      of the targeted cells because of specific ribonucleolytic activity against
      ribosomes of the engineered hirsutellin A variant. IMTXA33HtA3DeltaW represents a
      promising structure in the search for an improved immunotoxin without
      compromising the safety of patients.

PMID- 25752203
TI  - Comparison of the clinical characteristics and outcomes of Klebsiella pneumoniae
      and Streptococcus pneumoniae meningitis.
AB  - This multicenter, retrospective cohort study compared the clinical
      characteristics and outcomes of community-acquired Klebsiella pneumoniae
      meningitis (CA-KPM) with those of community-acquired Streptococcus pneumoniae
      meningitis (CA-SPM). Eighty-three adult patients, 27 with CA-KPM and 56 with CA
      SPM, were included. Diabetes mellitus (48.1% versus 21.4%; P=0.01) and liver
      cirrhosis (22.2% versus 5.4%; P=0.05) were more commonly associated with CA-KPM.
      Comatose mental status (40.7% versus 12.5%; P=0.01), septic shock (44.4% versus
      8.9%; P<0.001), and concomitant extrameningeal infections (40.7% versus 7.1%;
      P=0.001) were also more common in the CA-KPM group. The 28-day mortality (44.4%
      versus 10.7%; P<0.001) and inhospital mortality (51.9% versus 14.3%; P<0.001)
      were higher in the CA-KPM group. In conclusion, diabetes mellitus and liver
      cirrhosis are more common in the CA-KPM patients who were also more likely to
      present with severe manifestations and poor outcomes. 

PMID- 25752205
TI  - The effect of social isolation, gender and familiarity with the experimental
      procedure on tests of porcine nociceptive thresholds.
AB  - OBJECTIVE: To investigate the effects of habituation and isolation on mechanical
      nociceptive thresholds in pigs at the pelvic limbs and at the tail. STUDY DESIGN:
      Prospective randomized multifactorial study. ANIMALS: Thirty-two healthy
      castrated male (experiment 1), and 12 castrated male and 12 female (experiment 2)
      Danish Landrace*Yorkshire pigs, weighing 63.5+/-0.8 kg and 55.4+/-0.6 kg (the
      mean+/-SD, experiment 1 and 2, respectively). METHODS: Mechanical nociceptive
      thresholds were quantified with a von Frey anesthesiometer applied to two
      distinct anatomical regions (tail and pelvic limbs). Pigs receiving the
      mechanical challenge in the pelvic limbs were tested inside a cage, whereas pigs
      exposed to stimuli at the tail region were tested in an open arena. For both
      experiments, the effect of familiarity to the procedure was evaluated by
      comparing thresholds of nociception in habituated versus naive pigs. The presence
      of a companion animal was also evaluated in pigs receiving stimuli at the pelvic
      limbs. RESULTS: Pigs tested inside the cage were affected by the habituation to
      the procedure as indicated by the increase in willingness and time spent by the
      animals in the test cage. This effect was reflected in the lower mechanical
      nociceptive thresholds (medians with 25-75 percentiles) recorded for familiar
      pigs compared with naive animals [495 g (302-675) versus 745 g (479-1000),
      respectively; p=0.026]. Mechanical nociceptive thresholds measured at the tail of
      the pigs in the open arena were not affected by the familiarity of the animals
      with the experimental procedure. CONCLUSIONS AND CLINICAL RELEVANCE: The current
      results reiterate the value of habituation in research involving animal
      behaviour. Further characterization of the methodology is needed to allow its
      application in the evaluation of clinical conditions in pigs.

PMID- 25752206
TI  - Meta-analysis of associations between tumor necrosis factor-alpha polymorphisms
      and schizophrenia susceptibility.

PMID- 25752207
TI  - Personality disorders in adopted versus non-adopted adults.
AB  - The goal of this epidemiological study was to investigate lifetime history and
      odds ratios of personality disorders in adopted and non-adopted adults using a
      nationally representative sample. Data, drawn from the National Epidemiological
      Survey on Alcohol and Related Conditions (NESARC), were compared in adopted
      (n=378) versus non-adopted (n=42,503) adults to estimate the odds of seven
      personality disorders using logistic regression analyses. The seven personality
      disorders were histrionic, antisocial, avoidant, paranoid, schizoid, obsessive
      compulsive, and dependent personality disorder. Adoptees had a 1.81-fold increase
      in the odds of any personality disorder compared with non-adoptees. Adoptees had
      increased odds of histrionic, antisocial, avoidant, paranoid, schizoid, and
      obsessive-compulsive personality disorder compared with non-adoptees. Two risk
      factors associated with lifetime history of a personality disorder in adoptees
      compared to non-adoptees were (1) being in the age cohort 18-29 years (but no
      difference in the age 30-44 cohort), using the age 45 or older cohort as the
      reference and (2) having 12 years of education (but no difference in higher
      education groups), using the 0-11 years of education as the reference. These
      findings support the higher rates of personality disorders among adoptees
      compared to non-adoptees. 

PMID- 25752209
TI  - The role of positron emission tomography imaging in understanding Alzheimer's
      disease.
AB  - PET is a non-invasive imaging technique which allows the visualization and
      quantification of molecular processes, offering sensitive and early disease
      detection. Alzheimer's disease (AD) is a progressive neurodegenerative disorder
      leading to memory loss and other functional impairments. By employing different
      tracers targeting neurodegeneration, amyloid and tau aggregates, cholinergic
      neurotransmission, neuroinflammation and other processes, PET imaging enhances
      our understanding of the potential triggers of AD, the chronology of molecular
      events in AD, the detection of early AD, differentiation of AD dementia from
      other dementia disorders and the development of better drugs to treat AD. As
      such, PET imaging at different disease stages (asymptomatic, prodromal and
      dementia stages) is on its way to becoming a valuable routine clinical biomarker
      and a drug testing and research tool in AD. 

PMID- 25752210
TI  - Identification of candidate genes and mutations in QTL regions for immune
      responses in chicken.
AB  - There are two categories of immune responses - innate and adaptive immunity -
      both having polygenic backgrounds and a significant environmental component. In
      our study, adaptive immunity was represented by the specific antibody response
      toward keyhole limpet hemocyanin (KLH); innate immunity was represented by
      natural antibodies toward lipopolysaccharide (LPS) and lipoteichoic acid (LTA).
      Defining genetic bases of immune responses leads from defining quantitative trait
      loci (QTL) toward a single mutation responsible for variation in the phenotypic
      trait. The goal of the reported study was to define candidate genes and mutations
      for the immune traits of interest in chicken by performing an association study
      of SNPs located in candidate genes defined in QTL regions. Candidate genes and
      SNPs in QTL regions were selected in silico. SNP association was based on a
      custom SNP panel, GoldenGate genotyping assay (Illumina) and two statistical
      models: random mixed model and CAR score. The most significant SNP for immune
      response toward KLH was located in the JMJD6 gene located on GGA18. Four SNPs in
      candidate genes FOXJ1 (GGA18), EPHB1 (GGA9), PTGER4 (GGAZ) and PRKCB (GGA14)
      showed association with natural antibodies for LPS. A single SNP in ITGB4 (GGA18)
      was associated with natural antibodies for LTA. All associated SNPs mentioned
      above showed additive effects. 

PMID- 25752211
TI  - The effects of mode delivery on postpartum sexual function: a prospective study.
AB  - OBJECTIVE: To determine the effect of mode of delivery and perineal injury on
      sexual function at 6 and 12 months postpartum. DESIGN: Prospective cohort study.
      SETTING: Tertiary women's hospital in Melbourne, Australia. POPULATION: A cohort
      of 440 primigravid women. METHODS: The Female Sexual Function Index (FSFI) was
      completed at first visit (7-19 weeks of gestation), and at 6 and 12 months
      postpartum. MAIN OUTCOME MEASURES: A statistically significant difference in
      total FSFI or domain scores over time according to mode of delivery or perineal
      injury. RESULTS: In this cohort 54% of women had a normal vaginal delivery, 21%
      had an instrumental delivery, and 25% gave birth by caesarean section. No
      difference was found in total FSFI or domain scores according to mode of delivery
      over time between antenatal assessment and 12 months postpartum. Pain was
      decreased in the caesarean group only at 6 months postpartum. All groups showed
      pain scores at 12 months that were comparable with antenatal levels. For those
      who gave birth vaginally, 27% had an intact perineum, 50% had an episiotomy, and
      6%, 14%, and 3% had first, second, and third-degree tears, respectively. The only
      differences between groups were found over time according to perineal injury at 6
      months in the arousal domain. At 12 months, total FSFI and domain scores were no
      different to initial scores. CONCLUSIONS: At 12 months postpartum sexual function
      has returned to early pregnancy levels, irrespective of mode of delivery or
      perineal injury.

PMID- 25752212
TI  - Pretreatment platelet count early predicts extrahepatic metastasis of human
      hepatoma.
AB  - BACKGROUND & AIMS: Thrombocytosis is associated with metastasis in many human
      cancers. Most hepatocellular carcinomas (HCC) develop in cirrhotic livers, which
      are characterized by thrombocytopenia. We aimed to elucidate the pretreatment
      platelet count in prediction of extrahepatic metastasis of HCC during the follow
      up. METHODS: Three cohorts containing 1660, 480 and 965 HCC patients enrolled
      from three hospitals were used for discovery and validation respectively.
      Pretreatment clinical factors associated with extrahepatic metastasis during
      follow-up up to 5 years were identified using multivariate Cox regression model.
      RESULTS: In early-stage HCC (BCLC stage 0-A), pretreatment platelet count (hazard
      ratio [HR], 1.04 per 10,000/MUl; 95% CI, 1.01-1.07; P = 0.010) and serum alpha
      foetoprotein (AFP) >100 ng/ml (HR, 1.70; 95% CI, 1.04-2.78; P = 0.033) were the
      only two independent factors associated with extrahepatic metastasis. Receiver
      operating characteristic evidenced that pretreatment platelet count predicted
      metastasis better than AFP did. Survival tree analysis identified platelet counts
      <118,000/MUl (HR, 0.49; 95% CI, 0.38-0.63; P < 0.001) or >212,000/MUl (HR, 2.12;
      95% CI, 1.67-2.70; P < 0.001) to categorize patients into low and high risk of
      metastasis subgroups, which were verified using both validation cohorts.
      CONCLUSIONS: Pretreatment platelet count is a reliable marker to predict
      extrahepatic metastasis of early-stage HCC following curative treatment.
      Cirrhotic thrombocytopenia contributes to relatively low metastasis incidence of
      HCC than many other cancers. High platelet count identifies a subgroup of HCC
      patients at high risk of metastasis, who might benefit from adjuvant therapies
      following initial curative treatment.

PMID- 25752213
TI  - Portugal launches two PRT-FFPs to cover the local demands.

PMID- 25752214
TI  - Beneficial effect of cyclosporine A on traumatic hemorrhagic shock.
AB  - BACKGROUND: Vascular hyporeactivity plays an important role in severe trauma and
      shock. We investigated the beneficial effect of cyclosporine A (CsA) on traumatic
      shock and its relationship to vascular reactivity improvement and mitochondrial
      permeability transition pore (MPTP). MATERIALS AND METHODS: Sodium pentobarbital
      anesthetized rats were used to induce traumatic hemorrhagic shock by left femur
      fracture and hemorrhage, the beneficial effects of CsA (1, 5, and 10 mg/kg,
      intravenously) on animal survival, cardiovascular function, tissue blood
      perfusion, and mitochondrial function of vital organs were observed. In addition,
      hypoxia-treated vascular smooth muscle cells from normal rats were used to
      investigate the relationship of this beneficial effect of CsA to Rho-associated
      serine/threonine kinase (ROCK) and protein kinase C. RESULTS: CsA prolonged the
      survival time and increased the 24-h survival rate of traumatic hemorrhagic shock
      (31%, 56%, and 56% in 1, 5, and 10 mg/kg CsA group versus 25% in lactated Ringer
      solution group). Five milligrams per kilogram of CsA had the best effect, which
      stabilized and improved the hemodynamics, increased the tissue blood flow, and
      improved the liver and kidney function including its mitochondrial function in
      shock rats. CsA had no significant influences on the production of inflammatory
      mediators and cardiac output after traumatic hemorrhagic shock. Further results
      indicated that CsA significantly improved the vascular constriction and dilation
      reactivity of superior mesenteric artery to norepinephrine and acetylcholine,
      which was antagonized by ROCK inhibitor, Y27632, but not by protein kinase C
      inhibitor, staurosporine. Further studies showed that CsA restored hypoxia
      induced decrease of ROCK activity and inhibited the opening of MPTP in hypoxia
      treated vascular smooth muscle cells. CONCLUSIONS: CsA is beneficial for the
      treatment of traumatic hemorrhagic shock. The mechanism is mainly through
      improving the vascular reactivity, stabilizing the hemodynamics, and increasing
      tissue perfusion. This beneficial effect of CsA is related to the inhibitory
      effect of CsA on MPTP opening. ROCK is an important regulator molecule in this
      process.

PMID- 25752215
TI  - High Final Energy of Low-Level Gallium Arsenide Laser Therapy Enhances Skeletal
      Muscle Recovery without a Positive Effect on Collagen Remodeling.
AB  - The aim of this study was to evaluate the effects of a Gallium Arsenide (GaAs)
      laser, using a high final energy of 4.8 J, during muscle regeneration after
      cryoinjury. Thirty Wistar rats were divided into three groups: Control (C, n =
      10); Injured (I, n = 10) and Injured and laser treated (Injured/LLLT, n = 10).
      The cryoinjury was induced in the central region of the tibialis anterior muscle
      (TA). The applications of the laser (904 nm, 50 mW average power) were initiated
      24 h after injury, at energy density of 69 J cm(-1) for 48 s, for 5 days, to two
      points of the lesion. Twenty-four hours after the final application, the TA
      muscle was removed and frozen in liquid nitrogen to assess the general muscle
      morphology and the gene expression of TNF-alpha, TGF-beta, MyoD, and Myogenin.
      The Injured/LLLT group presented a higher number of regenerating fibers and fewer
      degenerating fibers (P < 0.05) without changes in the collagen remodeling. In
      addition, the Injured/LLLT group presented a significant decrease in the
      expression of TNF-alpha and myogenin compared to the injured group (P < 0.05).
      The results suggest that the GaAs laser, using a high final energy after
      cryoinjury, promotes muscle recovery without changing the collagen remodeling in
      the muscle extracellular matrix. 

PMID- 25752216
TI  - Editorial Comment from Mr Skarecky to Comparative investigation on clinical
      outcomes of robot-assisted radical prostatectomy between experienced open
      prostatic surgeons and novice open surgeons in a laparoscopically naive center
      with a limited caseload.

PMID- 25752217
TI  - Oncostatin M (OSM) protects against cardiac ischaemia/reperfusion injury in
      diabetic mice by regulating apoptosis, mitochondrial biogenesis and insulin
      sensitivity.
AB  - Oncostatin M (OSM) exhibits many unique biological activities by activating Obeta
      receptor. However, its role in myocardial I/R injury in diabetic mice remains
      unknown. The involvement of OSM was assessed in diabetic mice which underwent
      myocardial I/R injury by OSM treatment or genetic deficiency of OSM receptor
      Obeta. Its mechanism on cardiomyocyte apoptosis, mitochondrial biogenesis and
      insulin sensitivity were further studied. OSM alleviated cardiac I/R injury by
      inhibiting cardiomyocyte apoptosis through inhibition of inositol pyrophosphate 7
      (IP7) production, thus activating PI3K/Akt/BAD pathway, decreasing Bax expression
      while up-regulating Bcl-2 expression and decreasing the ratio of Bax to Bcl-2 in
      db/db mice. OSM enhanced mitochondrial biogenesis and mitochondrial function in
      db/db mice subjected to cardiac I/R injury. On the contrary, OSM receptor Obeta
      knockout exacerbated cardiac I/R injury, increased IP7 production, enhanced
      cardiomyocyte apoptosis, impaired mitochondrial biogenesis, glucose homoeostasis
      and insulin sensitivity in cardiac I/R injured diabetic mice. Inhibition of IP7
      production by TNP (IP6K inhibitor) exerted similar effects of OSM. The mechanism
      of OSM on cardiac I/R injury in diabetic mice is partly associated with IP7/Akt
      and adenine mononucleotide protein kinase/PGC-1alpha pathway. OSM protects
      against cardiac I/R Injury by regulating apoptosis, insulin sensitivity and
      mitochondrial biogenesis in diabetic mice through inhibition of IP7 production. 

PMID- 25752218
TI  - Autochthonous starter cultures and indigenous grape variety for regional wine
      production.
AB  - AIMS: To characterize Oenococcus oeni strains isolated from North-Apulian wines
      where malic acid degradation is usually achieved by spontaneous fermentations,
      and to determine the influence of bacterial inoculation time on the malolactic
      performances in 'Nero di Troia' wine using a complete autochthonous microbial
      regime. METHODS AND RESULTS: Oenococcus oeni strains from wines produced with the
      autochthonous (Apulia Region, southern Italy) grape variety 'Uva di Troia' were
      isolated, selected and characterized. Multilocus sequence typing and variable
      number tandem repeat analysis were used to investigate intraspecific diversity.
      Oenococcus oeni strains were tested in co-inoculation and in sequential
      inoculation, with two autochthonous yeast strains previously isolated from 'Nero
      di Troia' wine. After a preliminary screening using co-inoculation regime, the O.
      oeni strains were grouped in reason of the different behaviour in malic acid
      performances. Results suggested that the efficient degradation of malic acid in
      co-inoculation is a strain-dependent characteristic. CONCLUSIONS: Autochthonous
      yeast/bacterium combinations were identified as starter culture, and used in a co
      inoculation approach, for vinification of regional wines. SIGNIFICANCE AND IMPACT
      OF THE STUDY: The 'microbial terroir' of typical fermented food and beverage
      production represents a dynamic sector of applied research in food microbiology.
      In this work, we propose the use of autochthonous bacteria and yeast for wine
      production from an indigenous grape variety.

PMID- 25752219
TI  - The Impact of a Tiered Network on Hospital Choice.
AB  - OBJECTIVE: To evaluate the effect of a tiered network on hospital choice for
      scheduled admissions. DATA: The 2009-2012 patient-level claims data from Blue
      Cross Blue Shield of Massachusetts (BCBSMA). STUDY DESIGN: BCBSMA's three-tiered
      hospital network employs large differential cost sharing to encourage patients to
      seek care at hospitals on the preferred tier. During the study period, 44 percent
      of hospitals were moved to a different tier based on changes in cost or quality
      performance. We relied on this longitudinal variation for identification and
      specified conditional logit models to estimate the effect of the tiered network
      (TN) on patients' hospital choices relative to a non-TN comparison group.
      PRINCIPAL FINDINGS: The TN was associated with increased use of hospitals on the
      preferred and middle tiers relative to the nonpreferred tier for planned
      admissions. The results suggest that if all members were in a TN plan, relative
      to all members being in a non-TN plan, scheduled admissions to hospitals on the
      nonpreferred tier would drop by 7.6 percentage points, while those to middle and
      preferred tier hospitals would rise by 0.9 and 6.6 percentage points,
      respectively. CONCLUSION: Differential cost sharing can steer patients toward
      preferred hospitals for planned admissions.

PMID- 25752220
TI  - Reoperative median sternotomy following the use of a right internal mammary
      artery pedicle graft crossing the midline to the left anterior descending artery.
AB  - BACKGROUND AND AIM: The purpose of the present study was to examine the outcomes
      of cardiac reoperations for the patients with a previously placed pedicled graft
      of the right internal thoracic artery (RITA) to the left anterior descending
      artery (LAD). METHODS: Of 1002 consecutive patients who underwent isolated
      coronary bypass surgery, 612 patients received pedicled grafts of skeletonized
      RITA to the LAD crossing the midline over the aorta. Of this cohort, seven
      patients underwent cardiac reoperations via a median resternotomy including
      aortic valve replacement, mitral valve plasty, and total arch replacement.
      Covering the RITA with pericardium and mediastinal tissue had been routinely
      performed in the initial operation. RESULTS: Preoperative computed tomography
      (CT) angiography showed the RITA at a safe distance from the sternum in six
      patients. No graft injury occurred during dissection. The patient who underwent
      emergent total arch replacement died from global brain ischemia at postoperative
      day 11. The remaining six patients recovered well without major complication and
      survived at 7.5 +/- 4.5 years after reoperations. CONCLUSIONS: Cardiac
      reoperation via a median sternotomy can be performed at acceptable risk in
      patients with the RITA graft crossing the midline. Specific maneuvers should be
      applied in the first coronary artery bypass grafting to keep the RITA at the
      level of the aortic plane and prevent migration toward the sternum. Preoperative
      CT angiography is an important tool to understand the surgical anatomy and
      determine the safety of reoperation.

PMID- 25752221
TI  - The hidden killer: are we improving the management of bacteremia?

PMID- 25752222
TI  - Chikungunya infection: self-reported rheumatic morbidity and impaired quality of
      life persist 6 years later.
AB  - This study presents the 6-year follow-up of French gendarmes exposed to the
      chikungunya (CHIK) infection in 2006 on Reunion Island. The aim was to see to
      what extent the subjective health differences observed in 2008 (30 months after
      infection) between CHIK infected (CHIK+) and noninfected (CHIK-) gendarmes still
      persisted in 2012, and to investigate a possible return to a pre-CHIK health
      status for CHIK+ subjects. Gendarmes were contacted by mail in 2012 and asked to
      complete a self-questionnaire asking for morbidity, health care and medicines
      consumption since the last follow-up in 2008. Quality of life (QoL) after 6 years
      was evaluated using the SF-36 scale. In comparison with CHIK- subjects (n = 171),
      CHIK+ (n = 81) presented with higher rheumatic but also nonspecific morbidity
      such as headaches and fatigue associated with a large psychological impact,
      frequent depressive moods and social disabilities, leading to a significant
      impairment of the QoL and higher health care consumption. When restricted to
      CHIK+ subjects, comparing the data with that of 2008 showed persistent but
      decreasing self-reported rheumatic morbidity, and an increase over time of
      chronic discomfort (headache, fatigue) and depressive moods, resulting in no
      overall improvement in QoL. Despite possible cohort attrition bias, the
      comparability of CHIK+/CHIK- subjects allows the assumption of a long-term impact
      of CHIK infection with less chance of returning to a previous health status.
      Although these results may be specific to the 2006 virus strain, we recommend
      that public health strategies in the epidemic-prone countries include a response
      to the consequences of chronic post-CHIK disorders.

PMID- 25752223
TI  - Adult bacterial meningitis-a quality registry study: earlier treatment and
      favourable outcome if initial management by infectious diseases physicians.
AB  - Acute bacterial meningitis (ABM) is challenging for the admitting physician
      because it is a rare but fulminant disease, usually presenting without typical
      symptoms, and rapid treatment is pivotal. The purpose of this study was to
      evaluate the effect of initial management by infectious diseases (ID) physicians
      vs. non-ID physicians. A total of 520 consecutive adults (>17 years old), 110
      with initial ID management and 410 with non-ID management, registered in the
      Swedish quality registry for community-acquired ABM January 2008 to December
      2013, were analysed retrospectively. Primary outcome was appropriate treatment
      with antibiotics and corticosteroids <1 hour from admission. Secondary analyses
      were mortality during hospital stay and persisting neurological and hearing
      deficits at follow-up after 2 to 6 months. Differences in diagnostic treatment
      sequences also were analysed. Appropriate treatment <1 hour from admission was
      achieved significantly more often (41%) by ID physicians vs. non-ID physicians
      (24%) with an odds ratio (OR) of 2.4 (95% confidence interval [CI]: 1.40 to 4.14;
      p < 0.01) adjusted for confounders. The door-to-antibiotic time was significantly
      shorter, and significantly more patients were administered corticosteroids
      together with the first doses of antibiotics in the ID group. A trend of
      decreased mortality (4.5% vs. 8.0%) and sequelae at follow-up (24% vs. 44%;
      adjusted OR 0.55: 95% CI 0.31 to 1.00; p 0.05) were observed in the ID group vs.
      the non-ID group. Antibiotics were started without prior neuroimaging more often
      in the ID group (86% vs. 57%; p < 0.001). Initial management at the emergency
      department by ID physicians is associated with earlier appropriate treatment,
      more appropriate diagnostic treatment sequences and favourable outcome.

PMID- 25752224
TI  - The association of uterine cervical microbiota with an increased risk for
      cervical intraepithelial neoplasia in Korea.
AB  - Recent studies have suggested potential roles of the microbiome in cervicovaginal
      diseases. However, there has been no report on the cervical microbiome in
      cervical intraepithelial neoplasia (CIN). We aimed to identify the cervical
      microbiota of Korean women and assess the association between the cervical
      microbiota and CIN, and to determine the combined effect of the microbiota and
      human papillomavirus (HPV) on the risk of CIN. The cervical microbiota of 70
      women with CIN and 50 control women was analysed using pyrosequencing based on
      the 16S rRNA gene. The associations between specific microbial patterns or
      abundance of specific microbiota and CIN risk were assessed using multivariate
      logistic regression, and the relative excess risk due to interaction (RERI) and
      the synergy index (S) were calculated. The phyla Firmicutes, Actinobacteria,
      Bacteroidetes, Proteobacteria, Tenericutes, Fusobacteria and TM7 were predominant
      in the microbiota and four distinct community types were observed in all women. A
      high score of the pattern characterized by predominance of Atopobium vaginae,
      Gardnerella vaginalis and Lactobacillus iners with a minority of Lactobacillus
      crispatus had a higher CIN risk (OR 5.80, 95% CI 1.73-19.4) and abundance of A.
      vaginae had a higher CIN risk (OR 6.63, 95% CI 1.61-27.2). The synergistic effect
      of a high score of this microbial pattern and oncogenic HPV was observed (OR
      34.1, 95% CI 4.95-284.5; RERI/S, 15.9/1.93). A predominance of A. vaginae, G.
      vaginalis and L. iners with a concomitant paucity of L. crispatus in the cervical
      microbiota was associated with CIN risk, suggesting that bacterial dysbiosis and
      its combination with oncogenic HPV may be a risk factor for cervical neoplasia.

PMID- 25752225
TI  - The Elderhaus Program of All-inclusive Care for the Elderly in North Carolina:
      improving functional outcomes and reducing cost of care: preliminary data.
AB  - The Program of All-inclusive Care for the Elderly (PACE) is at a crossroads in
      its evolution as a community-based alternative to institutionally based nursing
      home care. Because of their perceived value and cost savings to Medicaid and
      Medicare, PACE programs are under increasing pressure to expand the numbers of
      individuals they serve while simultaneously reducing the overall cost of care.
      During the first 5 years of operations, the Elderhaus PACE Program in Wilmington,
      North Carolina, has reduced use of acute hospital care and skilled nursing home
      care while demonstrating that 46% of their participants improved and 20% of
      participants maintained their level of functional independence. It is felt that
      use of a plan of care organized according to standard domains of function and the
      quantifiable method of documenting improvement in functional health outcomes
      represent a critical factor in improved outcomes despite lower use of costly
      hospital and institutional care. The next step will be to disseminate the plan of
      care process to other PACE programs and measure its effect on participant
      functional outcomes and cost of care. The fact that the majority of PACE programs
      in North Carolina are using an electronic medical record that has the standard
      domains and quantitative functional measures embedded in the software will
      facilitate this step. Benchmarks for service use data are already being collected
      and will be compared with service use after the implementation of the plan of
      care process. 

PMID- 25752226
TI  - A survey of vitreous cell components performed using liquid-based cytology.
AB  - PURPOSE: To confirm the efficacy of liquid-based cytology (LBC) method in the
      observation of vitreous cells in various vitreoretinal diseases in human.
      METHODS: Vitreous fluid samples from 30 eyes were obtained by 23-gauge 3-port
      pars plana vitrectomy. After making three ports, we collected vitreous specimen
      from the core vitreous cavity without infusion. We divided the samples into a
      quiescent group and an active group based on clinical signs of inflammation. To
      confirm availability of LBC preparation slides for immunostaining, we also
      performed immunocytochemistry (ICC) for CD68, RPE65 and DEC-205 (CD205) using LBC
      slides of 10 cell-rich cases including retinal detachment and endophthalmitis.
      RESULTS: Using LBC method, small amounts of vitreous cells were observed
      efficiently. Vitreous cells were observed in inflammatory quiescent cases
      including macular pucker and macular hole. The number of vitreous cells increased
      significantly in the cases with clinically active inflammation (2297 versus 207
      cells/ml, respectively, p < 0.01, Mann-Whitney U-test). The ICC results showed
      the presence of CD68(+) cells in all 10 cases. Large numbers of DEC-205(+) cells
      were observed in one case with infectious endophthalmitis. In the cases with
      retinal detachment, the predominant cell type was RPE65(+) . Neutrophils and
      lymphocytes were also observed. CONCLUSIONS: The LBC method makes it possible to
      examine vitreous specimens easily and efficiently, facilitating the expedient
      diagnosis of vitreoretinal diseases, and the preparation slides are available for
      immunocytochemistry. This study also showed that vitreoretinal disease involves
      the migration of various types of cells including macrophages, neutrophils,
      lymphocytes, RPE65(+) pigmented cells and DEC-205(+) cells.

PMID- 25752227
TI  - Lateral Ventricle Volume Asymmetry Predicts Midline Shift in Severe Traumatic
      Brain Injury.
AB  - Midline shift following severe traumatic brain injury (sTBI) detected on computed
      tomography (CT) scans is an established predictor of poor outcome. We
      hypothesized that lateral ventricular volume (LVV) asymmetry is an earlier sign
      of developing asymmetric intracranial pathology than midline shift. This
      retrospective analysis was performed on data from 84 adults with blunt sTBI
      requiring a ventriculostomy who presented to a Level I trauma center. Seventy-six
      patients underwent serial CTs within 3 h and an average of three scans within the
      first 10 d of sTBI. Left and right LVVs were quantified by computer-assisted
      manual volumetric measurements. LVV ratios (LVR) were determined on the admission
      CT to evaluate ventricular asymmetry. The relationship between the admission LVR
      value and subsequent midline shift development was tested using receiver
      operating characteristic (ROC) analysis, and odds ratio (OR) and relative risk
      tests. Sixty patients had no >5 mm midline shift on the initial admission scan.
      Of these, 15 patients developed it subsequently (16 patients already had >5 mm
      midline shift on admission scans). For >5 mm midline shift development, admission
      LVR of >1.67 was shown to have a sensitivity of 73.3% and a specificity of 73.3%
      (area under the curve=0.782; p<0.0001). LVR of >1.67 as exposure yielded an OR of
      7.56 (p<0.01), and a risk ratio of 4.42 (p<0.01) for midline shift development as
      unfavorable outcome. We propose that LVR captures LVV asymmetry and is not only
      related to, but also predicts the development of midline shift already at
      admission CT examination. Lateral ventricles may have a higher "compliance" than
      midline structures to developing asymmetric brain pathology. LVR analysis is
      simple, rapidly accomplished and may allow earlier interventions to attenuate
      midline shift and potentially improve ultimate outcomes. 

PMID- 25752228
TI  - Stroke management: Informal caregivers' burdens and strians of caring for stroke
      survivors.
AB  - BACKGROUND AND AIMS: Stroke survivors live with varied degrees of disabilities
      and cares are provided largely by the informal caregivers. This study
      investigated informal caregivers' burden and strains of caring for stroke
      patients. METHOD: This study involved 157 (81 males and 76 females) informal
      caregivers of stroke survivors receiving care in all secondary and tertiary
      health institutions with physiotherapy services in Lagos State, Nigeria.
      Information was collected through self-administered questionnaire during clinic
      hours. Data was analyzed using Spearman's Rank Correlation Coefficient. RESULT:
      The patients' age ranged between 20 and 79 (mean=59.6 +/- 14.6 years). Sixty-one
      had haemorrhagic stroke while 96 had ischaemic stroke. The informal caregivers'
      age was 39.2 +/- 12.8 years (range: 17-36 years). More (60.8%) participants
      reported moderate objective while 79.2% had mild subjective burdens. The
      following factors significantly increased (P<0.05) the level of burden and
      strains experienced by the informal caregivers: closer intimacy with the stroke
      survivors, fewer number of caregivers for the stroke patient, longer duration
      since the onset of stroke and more hours of caregiving per day. Caregiving had
      negative significant influence (P<0.05) on the social, emotional, health and
      financial well-beings of the informal caregivers. CONCLUSION AND RECOMMENDATION:
      Caring for stroke survivors put social, emotional, health and financial burdens
      and strains on the informal caregivers. These burdens and strains increase with
      duration of stroke, intimacy, smaller number of caregivers and length of daily
      caregiving. Therefore, informal caregivers should be involved in the
      rehabilitation plan for stroke patients and their well-being should also be given
      adequate attention.

PMID- 25752229
TI  - Discriminating factors in fatal blunt trauma from low level falls and homicide.
AB  - PURPOSE: Determination of the manner of death is a major issue in forensic
      practice. Differentiating the injuries caused by falls from a low height from
      injuries due to the deliberate application of a blunt object can be difficult. A
      few studies suggested the use of certain criteria, such as the hat brim line
      rule, to help in differentiating between falls and blows. Unfortunately they are
      not consistent. METHODS: All autopsy cases from a 16-year period (1996-2012) were
      analyzed retrospectively. Three groups were defined: homicide cases (n = 31),
      sudden natural deaths involving a fall (n = 103), and accidental fall cases (n =
      30). The three groups were statistically compared across a wide range of
      parameters including general characteristics, presence, and characteristics of
      different types of wounds (lacerations, deep bruises, fractures, intracranial
      trauma, and defense injuries) as well as their respective anatomical site.
      RESULTS: There were marked differences in wounds between homicide and fall cases,
      e.g., wounds were more numerous and larger in homicides. We did not confirm the
      hat brim line rule as a reliable discriminating parameter. A simple and highly
      effective multivariate model was found, which included the presence of
      lacerations, deep bruises, and intracranial trauma. CONCLUSION: This study
      underlines the importance of autopsy findings in providing an indication of the
      manner of death. Conversely, the limitations of the hat brim line rule have been
      highlighted.

PMID- 25752230
TI  - Antibiotics may not decrease prostate-specific antigen levels or prevent
      unnecessary prostate biopsy in patients with moderately increased prostate
      specific antigen levels: A meta-analysis.
AB  - OBJECTIVES: To evaluate the effect of empiric antibiotics on decreasing prostate
      specific antigen (PSA) levels and the possibility of avoiding unnecessary
      prostate biopsies (PBs). MATERIALS AND METHODS: A systematic search of PubMed,
      Embase, and the Cochrane Library was performed to identify all randomized
      controlled trials (RCTs) that compared effects of empiric antibiotics with no
      treatment or placebo on lowering PSA levels and minimizing unnecessary PBs in
      patients with moderately increased PSA levels. The Cochrane Collaboration Review
      Manager software (RevMan 5.1.4) was used for statistical analysis. RESULTS: The
      inclusion criteria for the study were met by 6 RCTs (1 placebo controlled and 5
      no treatment controlled) involving 656 patients. The synthesized data from these
      RCTs indicated that there were no significant differences between the antibiotic
      and control groups in the PSA levels after treatment (mean difference [MD] =
      0.15, 95% CI:-0.50 to 0.81, P = 0.65], number of patients with decreased PSA
      levels after treatment (relative risk [RR] = 1.22, 95% CI: 0.90-1.65, P = 0.20],
      prostate-specific antigen density levels after treatment (MD =-0.04, 95% CI:-0.15
      to 0.07, P = 0.47), f/t% PSA after treatment (MD =-1.47, 95% CI:-4.65 to 1.71, P
      = 0.37), number of patients with responsive PSA (RR = 1.02, 95% CI: 0.58-1.81, P
      = 0.94), and individual Pca-positiverate in these patients (RR = 1.07, 95% CI:
      0.53-2.16, P = 0.86), and Pca-positiverates (RR = 0.85, 95% CI: 0.48-1.50, P =
      0.57). However, the antibiotic group had a significant change in the net PSA
      decrease after treatment compared with the control group (MD = 1.44, 95% CI: 0.70
      2.17, P = 0.0001). CONCLUSION: The use of empiric antibiotics may not
      significantly decrease PSA levels or avoid unnecessary PBs.

PMID- 25752231
TI  - Air oxidative radical hydroxysulfurization of styrenes leading to beta
      hydroxysulfides.
AB  - Air oxidative radical hydroxysulfurization of styrenes initiated by 0.5 mol % of
      tert-butyl hydroperoxide with arylthiols is described, and a new type of
      difunctionalization of alkenes was achieved. 

PMID- 25752232
TI  - Comparison of outcomes following complex posterior fossa surgery performed in the
      sitting versus lateral position.
AB  - The sitting position during surgery is thought to provide important advantages,
      yet it remains controversial. We compared surgical and neurological outcomes for
      patients operated on in the sitting versus lateral position. Technically
      difficult procedures performed from the years 2001-2008 for complex lesions in
      the posterior fossa (vestibular schwannomas, other cerebellopontine angle tumors,
      foramen magnum meningiomas, brainstem cavernomas, pineal region tumors) were
      included. Outcomes in the two surgical positions were compared for all 243
      patients (93 sitting, 38.3%; 150 lateral, 61.7%) and for 130/243 patients with
      vestibular schwannomas (50 sitting, 38.5%; 80 lateral, 61.5%). Sitting and
      lateral patient subgroups were clinically comparable. There were no surgical
      mortalities. The extent of removal and surgical and neurological outcomes were
      comparable. We found no advantage in surgical or neurological outcomes for use of
      the sitting or lateral surgical positions in technically difficult posterior
      fossa procedures. In vestibular schwannoma surgeries facial nerve preservation
      (House-Brackmann score 1-2) was related to extent of resection but not to
      surgical position. The choice of operative position should be based on lesion
      characteristics and the patient's preoperative medical status as well as the
      experience and preferences of the surgeons performing the procedure. 

PMID- 25752233
TI  - Mineralization of melamine and cyanuric acid as sole nitrogen source by newly
      isolated Arthrobacter spp. using a soil-charcoal perfusion method.
AB  - Melamine belongs to the s-triazine family, and industrially used as raw product
      in many ways all over the world. Melamine has been reported for human harmful
      effects and detected from some crops, soil and water. To remove melamine from the
      polluted environment, the efficient melamine-mineralizing microorganisms have
      been needed. We newly isolated three melamine-degrading bacteria from the same
      upland soil sample using soil-charcoal perfusion method. These bacteria were
      classified as Arthrobacter sp. MCO, Arthrobacter sp. CSP and Microbacterium sp.
      ZEL by 16S rRNA genes sequencing analysis. Both Arthrobacter species completely
      degraded melamine within 2 days, and consumed melamine as a sole nitrogen source.
      Both strains also grew in cyanuric acid as sole nitrogen source, and released
      small quantities of ammonium ions. These strains are the first identified
      bacteria that can mineralize both melamine and cyanuric acid as sole initial
      nitrogen source in Arthrobacter sp. Although ammeline and ammelide intermediates
      were detected, these strains possess none of the known genes encoding melamine
      degrading enzymes. Since the Arthrobacter strains also degraded melamine in a
      high pH liquid medium, they present as potential bioremediation agents in
      melamine-polluted environments.

PMID- 25752234
TI  - A novel metabolite (1,3-benzenediol, 5-hexyl) production by Exophiala spinifera
      strain FM through dibenzothiophene desulfurization.
AB  - Sulfur dioxide which is released from petroleum oil combustion causes pollution
      over the atmosphere and the soil. Biodesulfurization can be used as a
      complementary method of hydrodesulfurization, the common method of petroleum
      desulfurization in refineries. Many studies have been carried out to develop
      biological desulfurization of dibenzothiophene (DBT) with bacterial biocatalysts.
      However, fungi are capable to metabolize a wide range of aromatic hydrocarbons
      through cytochrome P450 and their extracellular enzymes. The aim of the present
      work was isolation and identification of fungi biocatalysts capable for DBT
      utilization as sulfur source and production of novel metabolites. DBT consumption
      and the related produced metabolites were analyzed by HPLC and GC-MS
      respectively. One of the isolated fungi that could utilize DBT as sole sulfur
      source was identified by both traditional and molecular experiments and
      registered in NCBI as Exophiala spinifera FM strain (accession no. KC952672).
      This strain could desulfurize 99 % of DBT (0.3 mM) as sulfur source by co
      metabolism reaction with other carbon sources through the same pathway as 4S and
      produced 2-hydroxy biphenyl (2-HBP) during 7 days of incubation at 30  degrees C
      and 180 rpm shaking. However, the isolate was able to transform 2-HBP to 1,3
      benzenediol, 5-hexyl. While biphenyl compounds are toxic to leaving cells,
      biotransformation of them can reduce their toxicity and the fungi will be more
      tolerant to the final product. These data are the first report about the
      desulfurization of DBT comparable to 4S-pathway and production of innovative
      metabolite by E. spinifera FM strain. 

PMID- 25752235
TI  - Potential probiotic attributes of a new strain of Bacillus coagulans CGMCC 9951
      isolated from healthy piglet feces.
AB  - A new strain of Bacillus coagulans CGMCC 9551, which has a broad range of
      antibacterial activities against six main pathogenic bacteria including
      Escherichia coli O8, Staphylococcus aureus, Salmonella enterica subsp. enterica
      serovar enteritidis, Streptococcus suis, Listeria monocytogenes and Pasteurella
      multocida, was isolated from healthy piglet feces. In adhesion assay, the isolate
      exhibited a stronger adhesion to pig intestinal mucus than that of B. subtilis
      JT143 and L. acidophilus LY24 respectively isolated from BioPlus((r))2B and
      FloraFIT((r)) Probiotics (P < 0.05). The adhesion activity reached 44.5 +/- 3.2,
      48.9 +/- 2.6, 42.6 +/- 3.3 and 37.6 +/- 2.4% to jejunum, ileum, transverse colon
      and sigmoid colon, separately. The survival rate of B. coagulans CGMCC 9551 was
      reduced by only 20% at 4 h exposure under 0.9% w/v bile salt. The strain was
      fully resistant to pH 2 for 2 h with 90.1 +/- 3.5% survival and susceptible to 15
      antibiotics commonly used in veterinary medicine. Additionally, the bacteria
      showed amylase, protease and cellulase activities. The safety assessment
      demonstrated the lack of toxicity potential in B. coagulans CGMCC 9551 by ligated
      rabbit ileal loop assay, acute and subchronic toxicity test. These results
      implied that that the new strain of B. coagulans CGMCC 9951 isolated from healthy
      piglet feces has promising probiotic characteristics and offers desirable
      opportunities for its successful commercialization as one excellent candidate
      probiotic.

PMID- 25752236
TI  - A rapid, one step molecular identification of Trichoderma citrinoviride and
      Trichoderma reesei.
AB  - Trichoderma species are widely used as production hosts for industrial enzymes.
      Identification of Trichoderma species requires a complex molecular biology based
      identification involving amplification and sequencing of multiple genes.
      Industrial laboratories are required to run identification tests repeatedly in
      cell banking procedures and also to prove absence of production host in the
      product. Such demands can be fulfilled by a brief method which enables
      confirmation of strain identity. This communication describes one step
      identification method for two common Trichoderma species; T. citrinoviride and T.
      reesei, based on identification of polymorphic region in the nucleotide sequence
      of translation elongation factor 1 alpha. A unique forward primer and common
      reverse primer resulted in 153 and 139 bp amplicon for T. citrinoviride and T.
      reesei, respectively. Simplification was further introduced by using mycelium as
      template for PCR amplification. Method described in this communication allows
      rapid, one step identification of two Trichoderma species.

PMID- 25752237
TI  - New data on the use of the FISH technique: the horizon dividing Spitz nevi and
      melanoma in childhood moves even further away.

PMID- 25752238
TI  - Some Controversies about Early Repolarization: The Haissaguerre Syndrome.
AB  - Controversy has followed the groundbreaking and cornerstone paper of Haissaguerre
      et al. Much of this controversy has been due to the use of the term "early
      repolarization pattern" and possible waveform morphologies on the standard 12
      lead ECG ( it is 10 second strip) that could predict who will manifest the
      malignant arrhythmogenic syndrome described by Haissaguerre et al. The standard
      ECG definition of early repolarization pattern (ERP) or early repolarization
      variant (ERV) since then has changed its clinical meaning for a surface
      electrocardiographic waveform from benign to malignant. The new definition of
      ERP/ERV contains only J wave but ST-segment elevation is no more obligatory. In
      the old definition, early repolarization pattern (ERP) or early repolarization
      variant (ERV) 3 is a well-recognized idiopathic electrocardiographic phenomenon
      considered to be present when at least two adjacent precordial leads show
      elevation of the ST segment, with values equal or higher than 1 mm. In the new
      electrocardiographic ERP concept, the ST segment may or may not be elevated and
      can be up-sloping, horizontal or down-sloping while in the old ERP/ERV concept it
      must be elevated at least 1 mm in at least two adjacent leads and the variant is
      characterized by a diffuse elevation of the ST segment of upper concavity, ending
      in a positive T wave of V2 to V4 or V5 and prominent J wave and ST-segment
      elevation predominantly in left precordial leads. The phenomenon constitutes a
      normal variant; it is almost a rule in athletes (present in 89% of the cases in
      this universe). 

PMID- 25752239
TI  - A new approach to modeling the influence of image features on fixation selection
      in scenes.
AB  - Which image characteristics predict where people fixate when memorizing natural
      images? To answer this question, we introduce a new analysis approach that
      combines a novel scene-patch analysis with generalized linear mixed models
      (GLMMs). Our method allows for (1) directly describing the relationship between
      continuous feature value and fixation probability, and (2) assessing each
      feature's unique contribution to fixation selection. To demonstrate this method,
      we estimated the relative contribution of various image features to fixation
      selection: luminance and luminance contrast (low-level features); edge density (a
      mid-level feature); visual clutter and image segmentation to approximate local
      object density in the scene (higher-level features). An additional predictor
      captured the central bias of fixation. The GLMM results revealed that edge
      density, clutter, and the number of homogenous segments in a patch can
      independently predict whether image patches are fixated or not. Importantly,
      neither luminance nor contrast had an independent effect above and beyond what
      could be accounted for by the other predictors. Since the parcellation of the
      scene and the selection of features can be tailored to the specific research
      question, our approach allows for assessing the interplay of various factors
      relevant for fixation selection in scenes in a powerful and flexible manner. 

PMID- 25752240
TI  - Quantitative functional characterization of conserved molecular interactions in
      the active site of mannitol 2-dehydrogenase.
AB  - Enzyme active site residues are often highly conserved, indicating a significant
      role in function. In this study we quantitate the functional contribution for all
      conserved molecular interactions occurring within a Michaelis complex for
      mannitol 2-dehydrogenase derived from Pseudomonas fluorescens (pfMDH). Through
      systematic mutagenesis of active site residues, we reveal that the molecular
      interactions in pfMDH mediated by highly conserved residues not directly involved
      in reaction chemistry can be as important to catalysis as those directly involved
      in the reaction chemistry. This quantitative analysis of the molecular
      interactions within the pfMDH active site provides direct insight into the
      functional role of each molecular interaction, several of which were unexpected
      based on canonical sequence conservation and structural analyses.

PMID- 25752241
TI  - The lateral pterygoid muscle affects reconstruction of the condyle in the
      sagittal fracture healing process: a histological study.
AB  - The purpose of this study was to verify the role of the lateral pterygoid muscle
      in the reconstruction of the condyle shape during the sagittal fracture healing
      process by histological methods. Twenty-four adult sheep underwent an osteotomy
      to create a sagittal fracture of the left condyle; the sheep were then divided
      randomly into two groups. The lateral pterygoid muscles of the sheep in the
      experimental group were maintained on the internal poles of the condyles, and
      their functions remained stable. The lateral pterygoid muscles of the sheep in
      the control group were cut, and their functions were blocked. The shape, erosion,
      and calcification of the condyles were observed and measured after 4, 12, and 24
      weeks of healing (n=4 from each group). The condyles were then submitted to
      haematoxylin and eosin, Ponceau S, and Sirius red studies. The results of the
      histology studies showed increased bone formation in the experimental group in
      which the functions of the lateral pterygoid muscle remained the same. The
      results of this study suggest that the lateral pterygoid muscle affects the
      reconstruction of the condylar shape during the healing process of a sagittal
      fracture of the mandibular condyle, and may even be involved in the formation of
      ankylosis. 

PMID- 25752242
TI  - The validity of using surface meshes for evaluation of three-dimensional
      maxillary and mandibular surgical changes.
AB  - The three-dimensional (3D) changes in hard tissue position following orthognathic
      surgery have been reported using 3D cephalometry, changes in volume, principal
      component analysis, and changes based on the surface model of the hard tissue.
      The aim of this study was to determine the validity of using surface models as a
      method of assessing positional changes of the maxilla and mandible. The actual
      unidirectional movement of the maxilla (advancement or downgraft) and the
      mandible (advancement), together with bidirectional movement of the maxilla
      (simultaneous advancement and downgraft) were simulated on a plastic skull.
      Following cone beam computed tomography scanning of each surgical simulation, the
      actual surgical movement was compared to the analysis based on surface model
      movement using the mean absolute distance of all points, the 90th percentile, and
      the root mean square (RMS) distance. All three methods of assessment of analysis
      consistently underestimated the actual amount of surgical movement. The movement
      was approximately one-third to one-half of the actual surgical movement. The use
      of surface meshes and point-to-point measurements grossly underestimates the 3D
      changes in the maxilla and mandible in simulated surgical procedures. Currently
      there are limitations in fully describing the true positional changes of the
      maxilla or the mandible in three dimensions. 

PMID- 25752245
TI  - Non-Markovian full counting statistics in quantum dot molecules.
AB  - Full counting statistics of electron transport is a powerful diagnostic tool for
      probing the nature of quantum transport beyond what is obtainable from the
      average current or conductance measurement alone. In particular, the non
      Markovian dynamics of quantum dot molecule plays an important role in the
      nonequilibrium electron tunneling processes. It is thus necessary to understand
      the non-Markovian full counting statistics in a quantum dot molecule. Here we
      study the non-Markovian full counting statistics in two typical quantum dot
      molecules, namely, serially coupled and side-coupled double quantum dots with
      high quantum coherence in a certain parameter regime. We demonstrate that the non
      Markovian effect manifests itself through the quantum coherence of the quantum
      dot molecule system, and has a significant impact on the full counting statistics
      in the high quantum-coherent quantum dot molecule system, which depends on the
      coupling of the quantum dot molecule system with the source and drain electrodes.
      The results indicated that the influence of the non-Markovian effect on the full
      counting statistics of electron transport, which should be considered in a high
      quantum-coherent quantum dot molecule system, can provide a better understanding
      of electron transport through quantum dot molecules. 

PMID- 25752243
TI  - The autism-associated chromatin modifier CHD8 regulates other autism risk genes
      during human neurodevelopment.
AB  - Recent studies implicate chromatin modifiers in autism spectrum disorder (ASD)
      through the identification of recurrent de novo loss of function mutations in
      affected individuals. ASD risk genes are co-expressed in human midfetal cortex,
      suggesting that ASD risk genes converge in specific regulatory networks during
      neurodevelopment. To elucidate such networks, we identify genes targeted by CHD8,
      a chromodomain helicase strongly associated with ASD, in human midfetal brain,
      human neural stem cells (hNSCs) and embryonic mouse cortex. CHD8 targets are
      strongly enriched for other ASD risk genes in both human and mouse
      neurodevelopment, and converge in ASD-associated co-expression networks in human
      midfetal cortex. CHD8 knockdown in hNSCs results in dysregulation of ASD risk
      genes directly targeted by CHD8. Integration of CHD8-binding data into ASD risk
      models improves detection of risk genes. These results suggest loss of CHD8
      contributes to ASD by perturbing an ancient gene regulatory network during human
      brain development. 

PMID- 25752244
TI  - Treatment of Breast and Prostate Cancer by Hypofractionated Radiotherapy:
      Potential Risks and Benefits.
AB  - Breast cancer and prostate cancer are the most common cancers diagnosed in women
      and men, respectively, in the UK, and radiotherapy is used extensively in the
      treatment of both. In vitro data suggest that tumours in the breast and prostate
      have unique properties that make a hypofractionated radiotherapy treatment
      schedule advantageous in terms of therapeutic index. Many clinical trials of
      hypofractionated radiotherapy treatment schedules have been completed to
      establish the extent to which hypofractionation can improve patient outcome. Here
      we present a concise description of hypofractionation, the mathematical
      description of converting between conventional and hypofractionated schedules,
      and the motivation for using hypofractionation in the treatment of breast and
      prostate cancer. Furthermore, we summarise the results of important recent
      hypofractionation trials and highlight the limitations of a hypofractionated
      treatment regimen.

PMID- 25752246
TI  - Assessment of the progression of tooth wear on dental casts.
AB  - Many methods are available for the grading of tooth wear, but their ability to
      assess the progression of wear over time has not been studied frequently. The aim
      was to assess whether the occlusal/incisal grading scale of the Tooth Wear
      Evaluation System (TWES) was sensitive enough for the detection of tooth wear
      progression from 14 to 23 years of age. A total of 120 sets of dental casts were
      gathered from 40 people, of whom impressions were made at 14, 18 and 23 years.
      The TWES was used to assess loss of clinical crown height throughout the entire
      dentition. There was a significant difference in the TWES scores between the
      three age groups on all teeth (Friedman tests; P < 0.005 in all cases). Post hoc
      Wilcoxon tests revealed that the difference between the scores between 14 and 18
      years and between 18 and 23 was significant for most teeth. It was concluded that
      the TWES is sensitive enough to detect changes in tooth wear over time.

PMID- 25752247
TI  - Binding energies of the pi-stacked anisole dimer: new molecular beam-laser
      spectroscopy experiments and CCSD(T) calculations.
AB  - Among noncovalent interactions, pi-pi stacking is a very important binding motif
      governed mainly by London dispersion. Despite its importance, for instance, for
      the structure of bio-macromolecules, the direct experimental measurement of
      binding energies in pi-pi stacked complexes has been elusive for a long time.
      Only recently, an experimental value for the binding energy of the anisole dimer
      was presented, determined by velocity mapping ion imaging in a two-photon
      resonant ionisation molecular beam experiment. However, in that paper, a
      discrepancy was already noted between the obtained experimental value and a
      theoretical estimate. Here, we present an accurate recalculation of the binding
      energy based on the combination of the CCSD(T)/CBS interaction energy and a DFT
      D3 vibrational analysis. This proves unambiguously that the previously reported
      experimental value is too high and a new series of measurements with a different,
      more sensitive apparatus was performed. The new experimental value of 1800+/-100
      cm(-1) (5.15+/-0.29 kcal mol(-1)) is close to the present theoretical prediction
      of 5.04+/-0.40 kcal mol(-1). Additional calculations of the properties of the
      cationic and excited states involved in the photodissociation of the dimer were
      used to identify and rationalise the difficulties encountered in the experimental
      work.

PMID- 25752248
TI  - [The relationship between Yoga Immersion, psychological well-being and
      psychiatric symptoms].
AB  - BACKGROUND: In recent years positive effects of Yoga (as a kind of spiritual
      exercise) in regards to subjective well-being and physical health can be found as
      well documented in the literature. METHOD: Based on a construct-psychological
      approach a newly developed scale for the assessment of Yoga involvement
      (immersion) was validated on a sample of 233 non-clinical subjects (210 females)
      by means of socio-demographic and well established psychometric parameters of
      psychological well-being and psychiatric symptoms. Furthermore, the group of yoga
      practitioners was compared with a control group consisting of 93 gymnastics
      practitioners (83 women) with respect to these parameters. RESULTS: The amount of
      Yoga Immersion (YI) can be reliably assessed by means of the one-dimensional YI
      scale (10 items) and shows to be strongly correlated with Mindfulness (r = .56; p
      < .01), Inner Correspondence (r = .61; p < .01) and Religious/Spiritual Well
      being (r = .68; p < .01). Furthermore highly yoga-immersive practitioners
      exhibited a significant higher amount of psychological well-being (p < .01)
      compared to marginally/moderately yoga-immersive and gymnastics practitioners.
      The Yoga-group also showed a lower amount of psychiatric symptoms (e.g.
      depression; p < .01). CONCLUSIONS: The globally postulated positive relationship
      between Yoga-practicing and mental health could be confirmed; thereby the impact
      of YI can be assumed as central. Further randomized controlled trial research
      focusing on the health/disease-related aspects of YI might be conducted
      especially in clinical groups.

PMID- 25752249
TI  - Microperimetric assessment of the two optical coherence tomography subtypes of
      acute macular neuroretinopathy.
AB  - BACKGROUND: This study evaluates the morpho-functional alterations associated
      with acute macular neuroretinopathy (AMNR). DESIGN: Prospective observational
      case series study carried out at the University Vita-Salute, Scientific Institute
      San Raffaele. PARTICIPANTS: Five out of six eyes (three patients) showed the
      typical features of AMNR. METHODS: The patients underwent an ophthalmological
      examination, including best-corrected visual acuity (BCVA) measurement,
      electroretinogram and electroculogram (ERG/EOG), multifocal electroretinogram
      (mfERG), infrared reflectance, short wavelength and near-infrared-fundus
      autofluorescence (SW-FAF/NIR-FAF), spectral-domain optical coherence tomography
      (SD-OCT) and microperimetry. MAIN OUTCOME MEASURE: Microperimetric alterations in
      the two SD-OCT subtypes of AMNR. RESULTS: The BCVA was 20/20 in all patients. ERG
      and EOG were normal; mfERG revealed a generally reduced response with a more
      reduced signal in the areas corresponding to the macular lesions. SD-OCT
      demonstrated two different patterns of retinal alterations. In case 1, SD-OCT
      revealed a hyperreflective, plaque-like band at the junction of the outer
      plexiform layer (OPL) and the inner nuclear layer (INL), extending into the INL
      (type 1 lesion). In cases 2 and 3, SD-OCT disclosed a hyperreflectivity of the
      OPL associated with outer nuclear layer thinning and disruption of the outer
      segment/retinal pigment epithelium junction (type 2 lesion). Microperimetry
      revealed a wide scotoma involving the entire macular area in all eyes, including
      the unaffected eye of case 1. The reduction in retinal sensitivity was greatest
      in type 1. CONCLUSIONS: SD-OCT confirms that AMNR may occur in different
      patterns. Microperimetry demonstrated that functional alterations are also
      discernible in apparently uninvolved areas. Both examinations are extremely
      valuable in characterizing the changes associated with AMNR.

PMID- 25752250
TI  - Radiofrequency energy deposition and radiofrequency power requirements in
      parallel transmission with increasing distance from the coil to the sample.
AB  - PURPOSE: We investigated global specific absorption rate (SAR) and radiofrequency
      (RF) power requirements in parallel transmission as the distance between the
      transmit coils and the sample was increased. METHODS: We calculated ultimate
      intrinsic SAR (UISAR), which depends on object geometry and electrical properties
      but not on coil design, and we used it as the reference to compare the
      performance of various transmit arrays. We investigated the case of fixing coil
      size and increasing the number of coils while moving the array away from the
      sample, as well as the case of fixing coil number and scaling coil dimensions. We
      also investigated RF power requirements as a function of lift-off, and tracked
      local SAR distributions associated with global SAR optima. RESULTS: In all cases,
      the target excitation profile was achieved and global SAR (as well as associated
      maximum local SAR) decreased with lift-off, approaching UISAR, which was constant
      for all lift-offs. We observed a lift-off value that optimizes the balance
      between global SAR and power losses in coil conductors. We showed that, using
      parallel transmission, global SAR can decrease at ultra high fields for finite
      arrays with a sufficient number of transmit elements. CONCLUSION: For parallel
      transmission, the distance between coils and object can be optimized to reduce
      SAR and minimize RF power requirements associated with homogeneous excitation.

PMID- 25752251
TI  - The direct and indirect effects of initial job status on midlife psychological
      distress in Japan: evidence from a mediation analysis.
AB  - In the current study, we investigated how initial job status at graduation from
      school is associated with midlife psychological distress, using microdata from a
      nationwide Internet survey of 3,117 men and 2,818 women aged 30-60 yr. We
      measured psychological distress using the Kessler 6 (K6) score (range: 0-24) and
      the binary variable of K6 score >=5. We found that unstable initial job status
      substantially raised midlife K6 scores and the probability of a K6 score >=5 for
      both men and women. Furthermore, our mediation analysis showed that for men,
      slightly less than 60% of the effect was mediated by current job status,
      household income, and marital status. For women, the effect of initial job status
      was somewhat lesser than that for men, and only 20-30% of it was mediated.
      Despite these gender asymmetries, the results indicated that initial job status
      was a key predictor of midlife mental health. The association between job status
      and mental health should be further investigated with special reference to the
      institutional attributes of the labor market and their socio-economic/demographic
      outcomes.

PMID- 25752252
TI  - Assessment of work intensification by managers and psychological distressed and
      non-distressed employees: a multilevel comparison.
AB  - Work intensification is a popular management strategy to increase productivity,
      but at the possible expense of employee mental stress. This study examines
      associations between ratings of work intensification and psychological distress,
      and the level of agreement between compared employee-rated and manager-rated work
      intensification. Multi-source survey data were collected from 3,064 employees and
      573 company managers from the private sector in 2010. Multilevel regression
      models were used to compare different work intensification ratings across
      psychological distress strata. Distressed employees rated higher degree of total
      work intensification compared to non-distressed employees, and on three out of
      five sub ratings there were an increased prevalence of work intensification in
      the case group. In general, there was poor agreement between employee and company
      work intensification rating. Neither manager-rated work intensification nor
      employee/manager discrepancy in work intensification ratings was associated with
      psychological distress. Distressed employees had a higher total score of
      employee/manager agreed work intensification, and a higher prevalence of
      increased demands of labour productivity. This study demonstrates higher ratings
      of employee/manager agreed work intensification in distressed employees compared
      to non-distressed employees, challenging previous findings of reporting bias in
      distressed employees' assessment of work environment.

PMID- 25752253
TI  - Occupational fatigue and other health and safety issues for young Australian
      workers: an exploratory mixed methods study.
AB  - Youth are vulnerable to sleep loss and fatigue due to biological, social and
      psychological factors. However, there are few studies addressing the risk that
      sleep loss and fatigue pose for youth in the workplace. The aim of this study was
      to explore work health and safety (WHS) issues for young workers and develop
      strategies and solutions for improved WHS outcomes, with a focus on issues
      related to fatigue, using a mixed-method, multi-stage approach. Participants
      either completed a survey (n=212) or took part in focus groups (n=115) addressing
      WHS for young workers, or attended a Future Inquiry Workshop (n=29) where
      strategies for improving youth WHS were developed. Fatigue was identified as a
      significant problem by the majority of young workers and was associated with
      unpredictable working time arrangements, precarious employment, high workload,
      working overtime and limited ability to self-advocate. Participants identified
      six key areas for action to improve WHS outcomes for young workers; 1) develop
      expertise, 2) give young workers a voice, 3) improve education and training, 4)
      build stakeholder engagement, 5) increase employer awareness of WHS
      responsibilities and, 6) improve processes for employers to manage and monitor
      WHS outcomes. The application of these directives to fatigue is discussed. 

PMID- 25752254
TI  - The protective effect of alpha-hederin, the active constituent of Nigella sativa,
      on tracheal responsiveness and lung inflammation in ovalbumin-sensitized guinea
      pigs.
AB  - Many investigations have demonstrated the prophylactic effect of Nigella sativa
      on asthma disease. One of its active constituents is alpha-hederin. In the
      present study, the preventive effect of two different concentrations of alpha
      hederin on tracheal responsiveness and lung inflammation in ovalbumin-sensitized
      guinea pigs was examined. Forty male adult Dunkin-Hartley guinea pigs were
      randomly divided into the control (C), sensitized (S) and sensitized pretreated
      groups with thymoquinone (3 mg/kg i.p., S + TQ), low-dose alpha-hederin (0.3
      mg/kg i.p., S + LAH) and high-dose alpha-hederin (3 mg/kg i.p., S + HAH). The
      responsiveness of tracheal smooth muscle (TR) to methacholine, histamine and
      ovalbumin was assessed. Moreover, total and differential white blood cell counts
      in lung lavage fluid were examined. Compared with the S group, the mean EC50
      value in the S + LAH group increased significantly (p < 0.05). The mean EC50
      value of histamine contraction in the S + LAH and S + HAH groups was
      significantly higher than in the S group (p < 0.05). In all pretreated groups,
      the TR to ovalbumin decreased in comparison to the S group (p < 0.001). Both the
      S + HAH and S + LAH groups showed significantly decreased TR compared to the S +
      TQ group (p < 0.01-p < 0.01). Total WBC and eosinophil counts in all pretreated
      groups decreased significantly in comparison with the S group (0.001-0.01). There
      was a significant increase in neutrophil, lymphocyte and monocyte counts in the
      pretreated groups compared to the S group (p < 0.001-p < 0.05). The basophil
      count in the S + TQ and S + HAH groups was significantly lower than in the S
      group (p < 0.01-p < 0.05). This study suggested that alpha-hederin has anti
      inflammatory and bronchodilatory effects like thymoquinone.

PMID- 25752255
TI  - Aortic arch repair today: open repair is best for most arch lesions.
AB  - The transverse aortic arch is challenging to repair by either evolving open or
      emerging endovascular approaches. Contemporary experience in aortic arch repair
      can be difficult to assess because clinical practice varies substantially among
      centers with regard to temperature targets for hypothermic circulatory arrest,
      temperature monitoring sites, circulating perfusate temperatures, cerebral
      perfusion monitoring techniques, perfusion catheter flow rates, cannulation
      sites, pH management, and protective pharmacologic agents. Repair of the aortic
      arch has changed substantially over the last decade; these changes appear to have
      substantially reduced patient risk. In general, contemporary outcomes of open
      aortic arch repair are good to excellent. When acute aortic dissection is absent,
      many centers report early mortality rates below 5%; when acute aortic dissection
      is present, these rates are doubled or tripled. Not unexpectedly, mortality rates
      for total transverse aortic arch repair with elephant trunk or frozen elephant
      trunk approaches are greater than those for hemiarch repair (7-17% vs. 3-4%). In
      contemporary reports of mixed hemiarch and total arch repairs for aortic
      aneurysm, several authors report early mortality rates and stroke rates below 5%.
      Surprisingly, mortality rates for reoperation are not unlike those for primary
      repair and range from 8% to 9%; however, the risk of stroke appears somewhat
      greater and ranges from 5% to 6%. 

PMID- 25752256
TI  - Treatment of renal artery aneurysms.
AB  - Renal artery aneurysms (RAAs) represent a rare disease and are most commonly
      discovered as an incidental imaging finding. RAA may be associated with
      hypertension and are usually asymptomatic at presentation but may result in
      rupture, hematuria, or renal infarction. The natural history of RAA is poorly
      understood. Although there is general consensus that RAA that are symptomatic or
      identified in women at risk for pregnancy should be repaired, diameter criteria
      for repair of asymptomatic RAA are controversial and emerging evidence suggests
      that rupture incidence is low for those <2.5 cm in diameter. Options for repair
      of RAA have expanded over the preceding decades with expansion of both open
      surgical and endovascular treatments. 

PMID- 25752257
TI  - Endovascular treatment of visceral artery aneurysms.
AB  - Visceral artery aneurysms (VAAs) are a rare entity; however, aneurysm rupture can
      be a catastrophic complication, which may lead to a mortality rate up to 90%.
      With the advent of endovascular technology and rapid development of endovascular
      materials, tailored endovascular therapy including embolization and placement of
      stents or stent grafts according to clinical presentation, anatomy of the
      aneurysm, and downstream organ, has become a promising alternative to open
      surgery. This review article summarizes the current state-of-the-art on
      endovascular treatment of VAAs. 

PMID- 25752258
TI  - Endovascular treatment of extracranial carotid artery aneurysms.
AB  - The objective of this article was to give a comprehensive overview over the
      different etiologies and the current techniques and results of endovascular
      treatment of aneurysms of the extracranial carotid artery. Extracranial carotid
      artery aneurysms are characterized by a low incidence but a high stroke rate in
      case of conservative management. Open surgical treatment has the disadvantage of
      a high percentage of postoperative cranial nerve injury and morbidity due to the
      cervical exposure. Endovascular treatment is attractive because of its less
      invasiveness. Due to the large variety of etiologies and different endovascular
      treatment approaches no comparative trials or even large retrospective studies do
      exist to determine the optimal treatment for the disease. This is a non
      systematic review of clinical case series and retrospective analysis about
      endovascular treatment of extracranial carotid artery aneurysms in English
      literature. 

PMID- 25752259
TI  - Biological organisation as closure of constraints.
AB  - We propose a conceptual and formal characterisation of biological organisation as
      a closure of constraints. We first establish a distinction between two causal
      regimes at work in biological systems: processes, which refer to the whole set of
      changes occurring in non-equilibrium open thermodynamic conditions; and
      constraints, those entities which, while acting upon the processes, exhibit some
      form of conservation (symmetry) at the relevant time scales. We then argue that,
      in biological systems, constraints realise closure, i.e. mutual dependence such
      that they both depend on and contribute to maintaining each other. With this
      characterisation in hand, we discuss how organisational closure can provide an
      operational tool for marking the boundaries between interacting biological
      systems. We conclude by focusing on the original conception of the relationship
      between stability and variation which emerges from this framework. 

PMID- 25752261
TI  - T-helper cell-mediated factors in drug-induced liver injury.
AB  - Drug-induced liver injury (DILI) leads to a large burden on the healthcare system
      due to its potential morbidity and mortality. The key for predicting and
      preventing DILI is to understand the underlying mechanisms. Hepatic inflammation
      is one of the most common features of DILI. The inflammation can be attributed to
      the innate immune response. The adaptive immune system is also affected by the
      innate immune response resulting in liver damage. T-helper cells are important
      regulators of acquired immunity. T-helper cell-mediated immune responses play
      pivotal roles in the pathogenesis of a variety of liver disorders. This review
      summarizes recent advances in the T-helper cell-mediated factors in DILI and
      potential mechanisms, which may lead to a better understanding of DILI.

PMID- 25752262
TI  - Relationship of pain and ancestry in African American women.
AB  - BACKGROUND: African Americans are reported to be more sensitive to pain than
      European Americans. Pain sensitivity has been shown to be genetically linked in
      animal models and is likely to be in humans. METHODS: Exactly, 11,239 self
      identified African American post-menopausal women enrolled in the Women's Health
      Initiative had percentage African ancestry determined by ancestry informative
      markers, "Pain Construct" measurements and covariate information. They answered
      five questions about specific types and location of pain, such as joint, neck,
      low back, headache and urinary. They also answered two questions which were used
      to derive a "Pain Construct", a measure of general pain scored on a scale of 1
      100. Associations were tested in linear regression models adjusting for age, self
      reported medical conditions, neighbourhood socio-economic status, education and
      depression. RESULTS: In the unadjusted model of the five specific types of pain
      measures, greater pain perception was associated with a higher proportion of
      African ancestry. However, some of the specific types of pain measures were no
      longer associated with African ancestry after adjustment for other study
      covariates. The Pain Construct was statistically significantly associated with
      African ancestry in both the unadjusted [beta = -0.132, 95% confidence interval
      (CI) = -099 to -0.164; r = -0.075, 95% CI -0.056 to -0.093] and the adjusted
      models (beta = -0.069 95% CI = -0.04 to -0.10). CONCLUSIONS: Greater African
      ancestry was associated with higher levels of self-reported pain, although this
      accounted for only a minor fraction of the overall variation in the Pain
      Construct.

PMID- 25752263
TI  - Effect of Nitrogen and Fluorine Co-substitution on the Structure and Magnetic
      Properties of Cr2 O3.
AB  - First-principles density functional calculations were carried out to determine
      the structure as well as electronic and magnetic properties of N and F co
      substituted Cr2 O3 . The formation of strong Cr?N bonds upon substitution of
      oxygen with nitrogen leads to large distortions in the local structure and
      changes in magnetic moments, which are partly compensated by co-substitution with
      fluorine. The effects of spin-orbit coupling are relatively weak, but its
      combination with local structural distortions gives rise to canting of spins and
      an overall magnetic moment in N, F co-substituted Cr2 O3 . Experimentally, we
      observe spin canting in N, F co-substituted Cr2 O3 with considerable enhancement
      in the coercive field at low temperatures. 

PMID- 25752264
TI  - Impact of increasing operative time on the incidence of early failure and
      complications following free tissue transfer? A risk factor analysis of 2,008
      patients from the ACS-NSQIP database.
AB  - BACKGROUND: There is a scarcity of externally valid data that investigate the
      utility of operative time, a common clinical parameter, as a predictor of free
      flap failures. Our aim was to assess whether prolonged operative time correlates
      with early flap failure following free tissue transfer in the acute care setting
      using the American College of Surgeons National Surgical Quality Improvement
      Program database. METHODS: The 2005-2011 American College of Surgeons National
      Surgical Quality Improvement Program databases were reviewed for encounters that
      entailed a free tissue transfer via a CPT algorithm. Patients identified as
      having a flap loss were compared with people who did not with regards to
      operative time and patient comorbidities. Patients were subdivided into the
      following cohort groups with regards to operative time: <6 hours, 6-12 hours, and
      >12 hours. Secondary outcome was association between increasing operative time
      and postoperative complications. RESULTS: Of the 2,008 patients identified, 62
      (3.1%) had early flap failure. After multivariable analysis, it was found that
      progressive operative time was associated with an increased risk of flap failure;
      6-12 hours odds ratio was 4.64 and >12 hours odds ratio was 5.65 (P = 0.0140).
      Higher American Society of Anesthesiologists class (P = 0.0042) was also shown to
      be significantly associated with flap failure. On secondary analysis, increasing
      operative time was correlated with the following complications: pneumonia, blood
      transfusions, prolonged ventilation, wound dehiscence, and wound complications.
      CONCLUSION: Our results, one of the largest series in the literature, revealed
      that prolonged operative time was associated with a stepwise increase in the
      likelihood of early flap failure as well certain postoperative complications. (c)
      2014 Wiley Periodicals, Inc. Microsurgery 37:12-20, 2017.

PMID- 25752265
TI  - Functional morphology of the primate head and neck.
AB  - The vertebral column plays a key role in maintaining posture, locomotion, and
      transmitting loads between body components. Cervical vertebrae act as a bridge
      between the torso and head and play a crucial role in the maintenance of head
      position and the visual field. Despite its importance in positional behaviors,
      the functional morphology of the cervical region remains poorly understood,
      particularly in comparison to the thoracic and lumbar sections of the spinal
      column. This study tests whether morphological variation in the primate cervical
      vertebrae correlates with differences in postural behavior. Phylogenetic
      generalized least-squares analyses were performed on a taxonomically broad sample
      of 26 extant primate taxa to test the link between vertebral morphology and
      posture. Kinematic data on primate head and neck postures were used instead of
      behavioral categories in an effort to provide a more direct analysis of our
      functional hypothesis. Results provide evidence for a function-form link between
      cervical vertebral shape and postural behaviors. Specifically, taxa with more
      pronograde heads and necks and less kyphotic orbits exhibit cervical vertebrae
      with longer spinous processes, indicating increased mechanical advantage for deep
      nuchal musculature, and craniocaudally longer vertebral bodies and more coronally
      oriented zygapophyseal articular facets, suggesting an emphasis on curve
      formation and maintenance within the cervical lordosis, coupled with a greater
      resistance to translation and ventral displacement. These results not only
      document support for functional relationships in cervical vertebrae features
      across a wide range of primate taxa, but highlight the utility of quantitative
      behavioral data in functional investigations.

PMID- 25752266
TI  - Analysis of repeated low-dose challenge studies.
AB  - Preclinical evaluation of candidate human immunodeficiency virus (HIV) vaccines
      entails challenge studies whereby non-human primates such as macaques are
      vaccinated with either an active or control vaccine and then challenged (exposed)
      with a simian-version of HIV. Repeated low-dose challenge (RLC) studies in which
      each macaque is challenged multiple times (either until infection or some maximum
      number of challenges is reached) are becoming more common in an effort to mimic
      natural exposure to HIV in humans. Statistical methods typically employed for the
      testing for a vaccine effect in RLC studies include a modified version of
      Fisher's exact test as well as large sample approaches such as the usual log-rank
      test. Unfortunately, these methods are not guaranteed to provide a valid test for
      the effect of vaccination. On the other hand, valid tests for vaccine effect such
      as the exact log-rank test may not be easy to implement using software available
      to many researchers. This paper details which statistical approaches are
      appropriate for the analysis of RLC studies, and how to implement these methods
      easily in SAS or R.

PMID- 25752267
TI  - Transoral robotic surgery for the excision of base of tongue vascular lesions.

PMID- 25752268
TI  - Endoscopic and histological features of gastric cancers after successful
      Helicobacter pylori eradication therapy.
AB  - BACKGROUND: Gastric cancer after successful Helicobacter pylori eradication
      therapy is often difficult to diagnose by endoscopy because of its indistinct
      borderline or lack of obviously cancerous characteristics. Furthermore, it has
      become evident that non-neoplastic epithelium covers cancerous areas in gastric
      cancer after eradication. Here, we investigated these endoscopic features and
      their relationship to histological findings. METHODS: We studied 24 and 47
      gastric cancers in patients who had (eradication group) and had not (control
      group) undergone H. pylori eradication, respectively. A gastritis-like appearance
      revealed by conventional endoscopy was defined as a mucosal pattern with no
      marked difference from the surrounding non-cancerous area and that revealed by
      narrow-band imaging (NBI)-magnifying endoscopy (ME) as the mucosal pattern
      observed in H. pylori-associated atrophic gastritis. We investigated a gastritis
      like appearance revealed by conventional endoscopy (A), a gastritis-like
      appearance at the margin (B) and within (C) the cancerous area revealed by NBI
      ME, and the histological characteristics of the overlying non-neoplastic
      epithelium. We also evaluated the relationship between endoscopic and
      histological findings in the eradication group. RESULTS: Endoscopy showed that
      features A, B and C were significantly more frequent in the eradication group (P
      = 0.031, P < 0.001, P < 0.001, respectively). Non-neoplastic epithelium covered
      more than 10 % of the cancerous area more frequently in the eradication group. In
      the eradication group, more than 90 % of cancers showing a gastritis-like
      appearance had non-neoplastic epithelium extending over 10 % of the cancerous
      area. CONCLUSION: Gastric cancer after successful H. pylori eradication tends to
      have gastritis-like features due to non-neoplastic epithelium covering the
      cancerous tissue.

PMID- 25752269
TI  - Gastrokine 1 inhibits gastrin-induced cell proliferation.
AB  - BACKGROUND: Gastrokine 1 (GKN1) acts as a gastric tumor suppressor. Here, we
      investigated whether GKN1 contributes to the maintenance of gastric mucosal
      homeostasis by regulating gastrin-induced gastric epithelial cell growth.
      METHODS: We assessed the effects of gastrin and GKN1 on cell proliferation in
      stable AGS(GKN1) and MKN1(GKN1) gastric cancer cell lines and HFE-145
      nonneoplastic epithelial cells. Cell viability and proliferation were analyzed by
      MTT and BrdU incorporation assays, respectively. Cell cycle and expression of
      growth factor receptors were examined by flow cytometry and Western blot
      analyses. RESULTS: Gastrin treatment stimulated a significant time-dependent
      increase in cell viability and proliferation in AGS(mock) and MKN1(mock), but not
      in HFE-145, AGS(GKN1), and MKN1(GKN1), cells, which stably expressed GKN1.
      Additionally, gastrin markedly increased the S-phase cell population, whereas
      GKN1 significantly inhibited the effect of gastrin by regulating the expression
      of G1/S cell-cycle regulators. Furthermore, gastrin induced activation of the NF
      kB and beta-catenin signaling pathways and increased the expression of CCKBR,
      EGFR, and c-Met in AGS and MKN1 cells. However, GKN1 completely suppressed these
      effects of gastrin via downregulation of gastrin/CCKBR/growth factor receptor
      expression. Moreover, GKN1 reduced gastrin and CCKBR mRNA expression in AGS and
      MKN1 cells, and there was an inverse correlation between GKN1 and gastrin, as
      well as between GKN1 and CCKBR mRNA expression in noncancerous gastric mucosae.
      CONCLUSION: These data suggest that GKN1 may contribute to the maintenance of
      gastric epithelial homeostasis and inhibit gastric carcinogenesis by
      downregulating the gastrin-CCKBR signaling pathway.

PMID- 25752270
TI  - Clinicopathological features of gastric cancer in young patients.
AB  - BACKGROUND: Early-onset gastric cancer is relatively rare. To evaluate the
      clinicopathological features and surgical outcome of young patients with gastric
      cancer, this retrospective comparative study was conducted. METHODS: From 2000 to
      2010, 4882 patients underwent surgery for gastric adenocarcinoma in our
      institution. A total of 136 patients under 40 years old were enrolled as the
      young group, and a total of 1435 patients aged between 60 and 69 were identified
      as the control group for this study. The patient's characteristics, pathological
      findings, surgical and clinical outcomes were reviewed, and the risk factors of
      recurrence were compared between the two groups. RESULTS: Among the young group,
      patients had significantly fewer comorbidities and postoperative complications.
      The patient proportion having 7 or more lymph node metastases was higher in the
      young group (25 %) than in the control group (16 %). The presence of lymph node
      metastasis was identified as a strong risk factor for recurrence (odds ratio =
      4.31) in the young group according to the results of the step-wise logistic
      regression analysis. Although the disease-specific survival at stage II was
      relatively better in the young group (p = 0.0439) than in the control group,
      there were no significant differences in overall survival for all stages.
      CONCLUSION: Early-onset gastric cancer is likely to present lymph node
      metastases. The survival rate of gastric cancer in young patients was equivalent
      to that in patients in their 60s, which is the typical age at onset.

PMID- 25752271
TI  - Micro-injector for capillary electrophoresis.
AB  - A novel micro-injector for capillary electrophoresis for the handling of samples
      with volumes down to as little as 300 nL was designed and built in our laboratory
      for analyses in which the available volume is a limitation. The sample is placed
      into a small cavity located directly in front of the separation capillary, and
      the injection is then carried out automatically by controlled pressurization of
      the chamber with compressed air. The system also allows automated flushing of the
      injection chamber as well as of the capillary. In a trial with a capillary
      electrophoresis system with contactless conductivity detector, employing a
      capillary of 25 MUm diameter, the results showed good stability of migration
      times and peak areas. To illustrate the technique, the fast separation of five
      inorganic cations (Na(+) , K(+) , NH4 (+) , Ca(2+) , and Mg(2+) ) was set up.
      This could be achieved in less than 3 min, with good limits of detection (10 MUM)
      and linear ranges (between about 10 and 1000 MUM). The system was demonstrated
      for the determination of the inorganic cations in porewater samples of a lake
      sediment core. 

PMID- 25752272
TI  - Strain-mediated electric-field control of exchange bias in a
      Co90Fe10/BiFeO3/SrRuO3/PMN-PT heterostructure.
AB  - The electric-field (E-field) controlled exchange bias (EB) in a Co90Fe10/BiFeO3
      (BFO)/SrRuO3/PMN-PT heterostructure has been investigated under different tensile
      strain states. The in-plane tensile strain of the BFO film is changed from +0.52%
      to +0.43% as a result of external E-field applied to the PMN-PT substrate. An
      obvious change of EB by the control of non-volatile strain has been observed. A
      magnetization reversal driven by E-field has been observed in the absence of
      magnetic field. Our results indicate that a reversible non-volatile E-field
      control of a ferromagnetic layer through strain modulated multiferroic BFO could
      be achieved at room temperature. 

PMID- 25752274
TI  - Bone: Elucidating which cell erythropoietin targets in bone.

PMID- 25752275
TI  - Obesity: High-fat binges lead to depot-specific activation of fat cell
      precursors.

PMID- 25752276
TI  - Neuroendocrinology: Leptin attenuates HPA-axis activation and stress responses.

PMID- 25752278
TI  - Cardiovascular disease: New nanomedicines for treating atherosclerotic plaques.

PMID- 25752279
TI  - Genetics: Epigenetic mechanisms underlying type 2 diabetes mellitus.

PMID- 25752281
TI  - Reproductive endocrinology: Menopausal hormone therapy-ovarian cancer risk
      revisited.

PMID- 25752283
TI  - The calcium-sensing receptor in bone--mechanistic and therapeutic insights.
AB  - The extracellular calcium-sensing receptor, CaSR, is a member of the G protein
      coupled receptor superfamily and has a critical role in modulating Ca(2+)
      homeostasis via its role in the parathyroid glands and kidneys. New evidence
      suggests that CaSR expression in cartilage and bone also directly regulates
      skeletal homeostasis. This Review discusses the role of CaSR in chondrocytes,
      through which CaSR contributes to the development of the cartilaginous growth
      plate, as well as in osteoblasts and osteoclasts, through which CaSR has effects
      on skeletal development and bone turnover in young and mature animals. The
      interaction of skeletal CaSR activation with parathyroid hormone (PTH), which is
      secreted by the parathyroid gland, can lead to net bone formation in trabecular
      bone or net bone resorption in cortical bone. Allosteric modulators of CaSR are
      beneficial in some clinical conditions, with effects that are mediated by the
      ability of these agents to alter levels of PTH and improve Ca(2+) homeostasis.
      However, further insights into the action of CaSR in bone cells might lead to
      CaSR-based drugs that maximize not only the effects of the receptor on the
      parathyroid glands and kidneys but also on bone. 

PMID- 25752284
TI  - The Critical Role of Dynamin-Related Protein 1 in Hypoxia-Induced Pulmonary
      Vascular Angiogenesis.
AB  - Pulmonary arterial hypertension (PAH) is a lethal disease characterized by
      pulmonary vascular obstruction due in part to excessive pulmonary artery
      endothelial cells (PAECs) migration and proliferation. The mitochondrial fission
      protein dynamin-related protein-1 (DRP1) has important influence on pulmonary
      vascular remodeling. However, whether DRP1 participates in the development and
      progression of pulmonary vascular angiogenesis has not been reported previously.
      To test the hypothesis that DRP1 promotes the angiogenesis via promoting the
      proliferation, stimulating migration, and inhibiting the apoptosis of PAECs in
      mitochondrial Ca(2+)-dependent manner, we performed following studies. Using
      hemodynamic analysis and morphometric assay, we found that DRP1 mediated the
      elevation of right ventricular systemic pressure (RVSP), right heart hypertrophy,
      and increase of pulmonary microvessels induced by hypoxia. DRP1 inhibition
      reversed tube network formation in vitro stimulated by hypoxia. The mitochondrial
      Ca(2+) inhibited by hypoxia was recovered by DRP1 silencing. Moreover, pulmonary
      vascular angiogenesis promoted by DRP1 was reversed by the specific mitochondrial
      Ca(2+) uniporter inhibitor Ru360. In addition, DRP1 promoted the proliferation
      and migration of PAECs in mitochondrial Ca(2+)-dependent manner. Besides, DRP1
      decreased mitochondrial membrane potential, reduced the DNA fragmentation, and
      inhibited the caspase-3 activation, which were all aggravated by Ru360.
      Therefore, these results indicate that the mitochondrial fission machinery
      promotes migration, facilitates proliferation, and prevents from apoptosis via
      mitochondrial Ca(2+)-dependent pathway in endothelial cells leading to pulmonary
      angiogenesis.

PMID- 25752285
TI  - Human endogenous retrovirus envelope proteins target dendritic cells to suppress
      T-cell activation.
AB  - Though mostly defective, human endogenous retroviruses (HERV) can retain open
      reading frames, which are especially expressed in the placenta. There, the
      envelope (env) proteins of HERV-W (Syncytin-1), HERV-FRD (Syncytin-2), and HERV-K
      (HML-2) were implicated in tolerance against the semi-allogenic fetus. Here, we
      show that the known HERV env-binding receptors ASCT-1 and -2 and MFSD2 are
      expressed by DCs and T-cells. When used as effectors in coculture systems, CHO
      cells transfected to express Syncytin-1, -2, or HML-2 did not affect T-cell
      expansion or overall LPS-driven phenotypic DC maturation, however, promoted
      release of IL-12 and TNF-alpha rather than IL-10. In contrast, HERV env
      expressing choriocarcinoma cell lines suppressed T-cell proliferation and LPS
      induced TNF-alpha and IL-12 release, however, promoted IL-10 accumulation,
      indicating that these effects might not rely on HERV env interactions. However,
      DCs conditioned by choriocarcinoma, but also transgenic CHO cells failed to
      promote allogenic T-cell expansion. This was associated with a loss of DC/T-cell
      conjugate frequencies, impaired Ca(2+) mobilization, and aberrant patterning of f
      actin and tyrosine phosphorylated proteins in T-cells. Altogether, these findings
      suggest that HERV env proteins target T-cell activation indirectly by modulating
      the stimulatory activity of DCs. 

PMID- 25752286
TI  - A very rare case of trisomy 4q32.3-4q35.2 and trisomy 21q11.2-21q22.11 in a
      patient with recombinant chromosomes 4 and 21.
AB  - We report the case of a patient with a clinical phenotype consistent with Down
      Syndrome (DS) who has a novel karyotypic abnormality. Karyotypic analyses were
      performed to investigate the cause of two spontaneous abortions. A balanced
      translocation between chromosomes 4 and 21 was identified, along with an
      additional abnormal chromosome 21. We performed high-resolution banding,
      comparative genomic hybridization (CGH), and FISH studies in both the patient and
      her mother to define the abnormality and determine its origin. CGH revealed a
      gain in copy number on the long arm of chromosome 4, spanning at least 24.4 Mb,
      and a gain in copy number on the long arm of chromosome 21, spanning at least
      16.2 Mb. FISH analysis using a chromosome 21 centromere probe and chromosome 4
      long arm telomere (4pter) probe confirmed the origin of the marker chromosome. It
      has been confirmed by the State Key Laboratory of Medical Genetics of China that
      this is the first reported instance of the karyotype
      47,XX,t(4;21)(q31.3;q11.2),+der(21)t(4;21)mat reported in the world.

PMID- 25752287
TI  - Identification and validation of gene module associated with lung cancer through
      coexpression network analysis.
AB  - Lung cancer, a tumor with heterogeneous biology, is influenced by a complex
      network of gene interactions. Therefore, elucidating the relationships between
      genes and lung cancer is critical to attain further knowledge on tumor biology.
      In this study, we performed weighted gene coexpression network analysis to
      investigate the roles of gene networks in lung cancer regulation. Gene
      coexpression relationships were explored in 58 samples with tumorous and matched
      non-tumorous lungs, and six gene modules were identified on the basis of gene
      coexpression patterns. The overall expression of one module was significantly
      higher in the normal group than in the lung cancer group. This finding was
      validated across six datasets (all p values <0.01). The particular module was
      highly enriched for genes belonging to the biological Gene Ontology category
      "response to wounding" (adjusted p value = 4.28 * 10(-10)). A lung cancer
      specific hub network (LCHN) consisting of 15 genes was also derived from this
      module. A support vector machine based on classification model robustly separated
      lung cancer from adjacent normal tissues in the validation datasets (accuracy
      ranged from 91.7% to 98.5%) by using the LCHN gene signatures as predictors.
      Eight genes in the LCHN are associated with lung cancer. Overall, we identified a
      gene module associated with lung cancer, as well as an LCHN consisting of hub
      genes that may be candidate biomarkers and therapeutic targets for lung cancer.
      This integrated analysis of lung cancer transcriptome provides an alternative
      strategy for identification of potential oncogenic drivers.

PMID- 25752288
TI  - Isolation and characterization of a catalase gene "HuCAT3" from pitaya
      (Hylocereus undatus) and its expression under abiotic stress.
AB  - Abiotic stresses usually cause H2O2 accumulation, with harmful effects, in
      plants. Catalase may play a key protective role in plant cells by detoxifying
      this excess H2O2. Pitaya (Hylocereus undatus) shows broad ecological adaptation
      due to its high tolerance to abiotic stresses, e.g. drought, heat and poor soil.
      However, involvement of the pitaya catalase gene (HuCAT) in tolerance to abiotic
      stresses is unknown. In the present study, a full-length HuCAT3 cDNA (1870 bp)
      was isolated from pitaya based on our previous microarray data and RACE method.
      The cDNA sequence and deduced amino acid sequence shared 73-77% and 75-80%
      identity with other plant catalases, respectively. HuCAT3 contains conserved
      catalase family domain and catalytic sites. Pairwise comparison and phylogenetic
      analysis indicated that HuCAT3 is most similar to Eriobotrya japonica CAT,
      followed by Dimocarpus longan CAT and Nicotiana tabacum CAT1. Expression profile
      analysis demonstrated that HuCAT3 is mainly expressed in green cotyledons and
      mature stems, and was regulated by H2O2, drought, cold and salt stress, whereas,
      its expression patterns and maximum expression levels varied with stress types.
      HuCAT activity increased as exposure to the tested stresses, and the fluctuation
      of HuCAT activity was consistent with HuCAT3 mRNA abundance (except for 0.5 days
      upon drought stress). HuCAT3 mRNA elevations and HuCAT activities changes under
      cold stress were also in conformity with the cold tolerances among the four
      genotypes. The obtained results confirmed a major role of HuCAT3 in abiotic
      stress response of pitaya. This may prove useful in understanding pitaya's high
      tolerance to abiotic stresses at molecular level.

PMID- 25752289
TI  - Population genetics of non-genetic traits: evolutionary roles of stochasticity in
      gene expression.
AB  - The role of stochasticity in evolutionary genetics has long been debated. To
      date, however, the potential roles of non-genetic traits in evolutionary
      processes have been largely neglected. In molecular biology, growing evidence
      suggests that stochasticity in gene expression (SGE) is common and that SGE has
      major impacts on phenotypes and fitness. Here, we provide a general overview of
      the potential effects of SGE on population genetic parameters, arguing that SGE
      can indeed have a profound effect on evolutionary processes. Our analyses suggest
      that SGE potentially alters the fate of mutations by influencing effective
      population size and fixation probability. In addition, a genetic control of SGE
      magnitude could evolve under certain conditions, if the fitness of the less-fit
      individual increases due to SGE and environmental fluctuation. Although empirical
      evidence for our arguments is yet to come, methodological developments for
      precisely measuring SGE in living organisms will further advance our
      understanding of SGE-driven evolution. 

PMID- 25752290
TI  - Interleukin 18 augments growth ability via NF-kappaB and p38/ATF2 pathways by
      targeting cyclin B1, cyclin B2, cyclin A2, and Bcl-2 in BRL-3A rat liver cells.
AB  - Interleukin 18 (IL-18) is a pleiotropic cytokine and capable of stimulating
      proliferation of certain cell types. Nonetheless, its effect on normal liver
      cells cultured remains unclear. In the present study, we discovered that IL-18
      expression level was remarkably elevated at 3.3 and 8.6h after synchronized BRL
      3A rat liver cells (G0 phase) re-entering the cell cycle. In addition,
      recombinant rat IL-18 (rrIL-18) at dosages 5-10 ng/ml increased the cell
      viability compared to untreated cells (with medium only) at 24 and 48 h (P<0.05).
      At the same time, the percentage of BrdU-labeling cells was also significantly
      increased (P<0.01). On the other hand, knockdown of IL-18 expression with short
      interference RNA (siRNA), the cell viability began to decline at 24h and
      significantly decreased compared to negative control (NC) at 48 and 72 h after
      transfection (P<0.05). Meanwhile, the number of cells in division phase (G2/M)
      was reduced in parallel. Further, after treatment with rrIL-18 (5 ng/ml), IL-18
      and its receptor subunit IL-18Ralpha increased both at mRNA and protein levels.
      Moreover, the expression levels of adaptor molecule MyD88, transcription factor
      NF-kappaB and its downstream targets cyclin B1 and cyclin B2 were remarkably
      enhanced in BRL-3A cells stimulated by rrIL-18. Furthermore, transcription factor
      ATF2 and its targeted genes cyclin A2, Bcl-2 were also markedly increased after
      treatment with rrIL-18. These results demonstrated that IL-18 can augment cell
      proliferation via NF-kappaB and p38/ATF2 pathway by targeting cyclin B1, cyclin
      B2, cyclin A2 and Bcl-2 in BRL-3A rat liver cells.

PMID- 25752291
TI  - The APOE promoter polymorphism is associated with rebleeding after spontaneous
      SAH in a Chinese population.

PMID- 25752292
TI  - Inelastic electron irradiation damage in hexagonal boron nitride.
AB  - We present a study of the inelastic effects caused by electron irradiation in
      monolayer hexagonal boron nitride (h-BN). The data was obtained through in situ
      experiments performed inside a low-voltage aberration-corrected transmission
      electron microscope (TEM). By using various specialized sample holders, we study
      defect formation and evolution with sub-nanometer resolution over a wide range of
      temperatures, between -196 and 1200  degrees C, highlighting significant
      differences in the geometry of the structures that form. The data is then
      quantified, allowing insight into the defect formation mechanism, which is
      discussed in comparison with the potential candidate damage processes. We show
      that the defect shapes are determined by an interplay between electron damage,
      which we assign to charging, and thermal effects. We additionally show that this
      damage can be avoided altogether by overlapping the samples with a monolayer of
      graphene, confirming this for h-BN and providing a way to overcome the well-known
      fragility of h-BN under the electron beam.

PMID- 25752294
TI  - First evidence for the existence of hexafluoroantimonic(v) acid.
AB  - By reacting IPr?InBr3 with AgSbF6 in dichloroethane at room temperature, we could
      obtain single crystals comprising [{(IPr?InBr3 )(Ag?(CH2 Cl)2 )}2 ][SbF6 ]2 (1)
      and two identical HSbF6 units. It is presumed that the reaction gave rise to
      [IPr?InBr3-x ][SbF6 ]x (x=1, 2, or 3) which reacted with adventitious water to
      give HSbF6 and [IPr?InBr3-x (OH)][SbF6 ]x-1 . The experiment was reproduced at 60
      degrees C, eventually leading to the indium hydroxide [{IPr?In(OH)0.5 (H2 O)4.5
      }2 ][SbF6 ]5 (2). 

PMID- 25752293
TI  - Double emulsions to improve frankfurter lipid content: impact of perilla oil and
      pork backfat.
AB  - BACKGROUND: The technology involving the use of water-in-oil-in-water double
      emulsions (DEs) offers an interesting approach to improve the fat content of
      foods. With this aim, the effect on frankfurter properties of replacing pork
      backfat with two different DEs prepared using perilla oil and pork backfat as
      lipid phases was assessed. This strategy was compared with straightforward
      addition of the lipid source and addition by means of an oil-in-water (O/W)
      emulsion. RESULTS: As compared with all-pork-fat frankfurters, the ones with
      perilla oil had a higher proportion of n-3 polyunsaturated fatty acids. Reduced
      fat frankfurters had similar water- and fat-binding properties irrespective of
      the lipid source or the technological strategy used to incorporate it. Moreover,
      the oil source but not its mode of incorporation determined the oxidation levels
      of frankfurters. In reduced-fat samples, except in the case of frankfurters
      formulated with a perilla oil-in-water emulsion, hardness was unaffected either
      by the type of fat or by its mode of incorporation. The replacement of pork
      backfat by perilla oil reduced the overall acceptability of products when perilla
      oil was added by means of the O/W emulsion and DE approaches. CONCLUSION: This
      technology is suitable for labelling meat products with specific nutritional and
      health claims.

PMID- 25752295
TI  - Oral squamous cancer cell exploits hnRNP A1 to regulate cell cycle and
      proliferation.
AB  - Oral squamous cell carcinoma (OSCC) is a common human malignant tumor with high
      mortality. So far, the molecular pathogenesis of OSCC remains largely unclear.
      Heterogeneous nuclear ribonucleoprotein (hnRNP) A1 is an important multi-function
      splicing factor and closely related to tumorigenesis. hnRNP A1 is overexpressed
      in various tumors, and promotes aerobic glycolysis and elongation of telomere,
      but the function of hnRNP A1 in cell cycle and proliferation remains unclear. We
      found that hnRNP A1 was overexpressed in OSCC tissues, and was required for the
      growth of OSCC cells. Moreover, hnRNP A1 was highly expressed in the G2/M cell
      cycle phase. Knockdown of hnRNP A1 induced G2/M arrest. DNA microarray assay
      result showed that hnRNP A1 regulated the expression of a number of target genes
      associated with G2/M phase. Moreover, hnRNP A1 controlled the alternative
      splicing of CDK2 exon 5. These findings suggested that hnRNP A1 plays key roles
      in the regulation of cell cycle progression and pathogenesis of OSCC.

PMID- 25752296
TI  - Adsorption of insoluble polysulfides Li2S(x) (x = 1, 2) on Li2S surfaces.
AB  - In lithium-sulfur batteries, the growth of insulating discharge product Li2S film
      affects the cathode microstructure and the related electron as well as lithium
      ion transport properties. In this study, chemical reactions of insoluble lithium
      polysulfides Li2Sx (x = 1, 2) on crystal Li2S substrate are investigated by a
      first-principles approach. First-principles atomistic thermodynamics predicts
      that the stoichiometric (111) and (110) surfaces are stable around the operating
      cell voltage. Li2Sx adsorption is an exothermic reaction with the (110) surface
      being more active to react with the polysulfides than the stoichiometric (111)
      surface. There is no obvious charge transfer between the adsorbed molecule and
      the crystal Li2S substrate. Analysis of the charge density difference suggests
      that the adsorbate interacts with the substrate via a strong covalent bond. The
      growth mechanism of thermodynamically stable surfaces is investigated in the
      present study. It is found that direct Li2S deposition is energetically favored
      over Li2S2 deposition and reduction process. 

PMID- 25752297
TI  - Preventive Ethics Through Expanding Education.
AB  - Healthcare institutions have been making increasing efforts to standardize
      consultation methodology and to accredit both bioethics training programs and the
      consultants accordingly. The focus has traditionally been on the ethics
      consultation as the relevant unit of ethics intervention. Outcome measures are
      studied in relation to consultations, and the hidden assumption is that
      consultations are the preferred or best way to address day-to-day ethical
      dilemmas. Reflecting on the data from an internal quality improvement survey and
      the literature, we argue that having general ethics education as a key function
      of ethics services may be more important in meeting the contemporaneous needs of
      acute care settings. An expanded and varied ethics education, with attention to
      the time constraints of healthcare workers' schedules, was a key recommendation
      brought forward by survey respondents. Promoting ethical reflection and creating
      a culture of ethics may serve to prevent ethical dilemmas or mitigate their
      effects. 

PMID- 25752298
TI  - Encapsulation of S/SWNT with PANI web for enhanced rate and cycle performance in
      lithium sulfur batteries.
AB  - Lithium-sulfur batteries show great potential to compete with lithium-ion
      batteries due to the fact that sulfur can deliver a high theoretical capacity of
      1672 mAh/g and a high theoretical energy density of 2500 Wh/kg. But it has
      several problems to be solved in order to achieve high sulfur utilization with
      high Coulombic efficiency and long cycle life of Li-S batteries. These problems
      are mainly caused by the dissoluble polysulfide species, which are a series of
      complex reduced sulfur products, associating with shuttle effect between
      electrodes as well as side reactions on lithium metal anode. To alleviate these
      challenges, we developed a sulfur-carbon nanotube (S/SWNT) composite coated with
      polyaniline (PANI) polymer as polysulfide block to achieve high sulfur
      utilization, high Coulombic efficiency, and long cycle life. The PANI coated
      S/SWNT composite showed a superior specific capacity of 1011 mAh/g over 100
      cycles and a good rate retention, demonstrating the synergic contribution of
      porous carbon and conducting polymer protection to address challenges underlying
      sulfur cathode. 

PMID- 25752299
TI  - Polysialic acid on SynCAM 1 in NG2 cells and on neuropilin-2 in microglia is
      confined to intracellular pools that are rapidly depleted upon stimulation.
AB  - NG2 cells comprise a heterogeneous precursor population but molecular markers
      distinguishing between the assumed NG2 cell subpopulations are lacking.
      Previously, we described that a subfraction of the synaptic cell adhesion
      molecule SynCAM 1 is modified with the glycan polysialic acid (polySia) in NG2
      cells. As for its major carrier, the neural cell adhesion molecule NCAM, polySia
      attenuates SynCAM 1 adhesion. Functions, as well as cellular and subcellular
      distribution of polySia-SynCAM 1 are elusive. Using murine glial cultures we now
      demonstrate that polySia-SynCAM 1 is confined to the Golgi compartment of a
      subset of NG2 cells and transiently recruited to the cell surface in response to
      depolarization. NG2 cells with Golgi-confined polySia were NCAM-negative, but
      positive for markers of oligodendrocyte precursor cells (OPCs). Consistent with
      previous data on polySia-SynCAM 1, polySia in Ncam(-/-) NG2 cells was exclusively
      attached to N-glycans and synthesized by ST8SIA2, one out of two mammalian
      polysialyltransferases. Unexpectedly, Golgi-confined polySia was also detected in
      Ncam(-/-) microglia, but this fraction resided on O-glycans and was produced by
      the second polysialyltransferase, ST8SIA4, indicating the presence of yet another
      polySia carrier in microglia. Searching for this carrier, we identified
      polysialylated neuropilin-2, so far only known from dendritic cells and exudate
      macrophages. Microglia activation by LPS, but not interleukin-4, caused a
      transient translocation of Golgi-localized polySia to the cell surface, resulting
      in complete depletion. Finally, NO-production of LPS-stimulated microglia was
      attenuated by addition of polySia suggesting that the observed loss of polySia
      neuropilin-2 is involved in negative feedback regulation of pro-inflammatory
      microglia polarization.

PMID- 25752300
TI  - Comparative histology of the adult electric organ among four species of the genus
      Campylomormyrus (Teleostei: Mormyridae).
AB  - The electric organ (EO) of weakly electric mormyrids consists of flat, disk
      shaped electrocytes with distinct anterior and posterior faces. There are
      multiple species-characteristic patterns in the geometry of the electrocytes and
      their innervation. To further correlate electric organ discharge (EOD) with EO
      anatomy, we examined four species of the mormyrid genus Campylomormyrus
      possessing clearly distinct EODs. In C. compressirostris, C. numenius, and C.
      tshokwe, all of which display biphasic EODs, the posterior face of the
      electrocytes forms evaginations merging to a stalk system receiving the
      innervation. In C. tamandua that emits a triphasic EOD, the small stalks of the
      electrocyte penetrate the electrocyte anteriorly before merging on the anterior
      side to receive the innervation. Additional differences in electrocyte anatomy
      among the former three species with the same EO geometry could be associated with
      further characteristics of their EODs. Furthermore, in C. numenius, ontogenetic
      changes in EO anatomy correlate with profound changes in the EOD. In the juvenile
      the anterior face of the electrocyte is smooth, whereas in the adult it exhibits
      pronounced surface foldings. This anatomical difference, together with
      disparities in the degree of stalk furcation, probably contributes to the about
      12 times longer EOD in the adult. 

PMID- 25752301
TI  - Real-time monitoring of cancer cell metabolism and effects of an anticancer agent
      using 2D in-cell NMR spectroscopy.
AB  - Altered metabolism is a critical part of cancer cell properties, but real-time
      monitoring of metabolomic profiles has been hampered by the lack of a facile
      method. Here, we propose real-time metabolomic monitoring of live cancer cells
      using (13) C6 -glucose and heteronuclear two-dimensional (2D) NMR. The method
      allowed for metabolomic differentiation between cancer and normal cells on the
      basis of time-dependent changes in metabolite concentrations. Cancer cells were
      found to have large in- and out-flux of pyruvate as well as increased net
      production of alanine and acetate. The method also enabled evaluation of the
      metabolic effects of galloflavin whose anticancer effects have been attributed to
      its specific inhibition of lactate dehydrogenase. Our approach revealed
      previously unknown functional targets of galloflavin, which were further
      confirmed at the protein levels. Our method is readily applicable to the study of
      metabolic alterations in other cellular disease model systems. 

PMID- 25752303
TI  - What's really new in the field of vascular access? Towards a global use of
      ultrasound.

PMID- 25752302
TI  - Mechanical ventilation during extracorporeal life support (ECLS): a systematic
      review.
AB  - PURPOSE: In patients with acute respiratory distress syndrome (ARDS),
      extracorporeal life support (ECLS) has been utilized to support gas exchange and
      mitigate ventilator-induced lung injury (VILI). The optimal ventilation settings
      while on ECLS are unknown. The purpose of this systematic review is to describe
      the ventilation practices in patients with ARDS who require ECLS. METHODS: We
      electronically searched MEDLINE, EMBASE, CENTRAL, AMED, and HAPI (inception to
      January 2015). Studies included were randomized controlled trials, observational
      studies, or case series (>=4 patients) of ARDS patients undergoing ECLS. Our
      review focused on studies describing ventilation practices employed during ECLS
      for ARDS. RESULTS: Forty-nine studies (2,042 patients) met our inclusion
      criteria. Prior to initiation of ECLS, at least one parameter consistent with
      injurious ventilation [tidal volume >8 mL/kg predicted body weight (PBW), peak
      pressure >35 cmH2O (or plateau pressure >30 cmH2O), or FiO2 >=0.8] was noted in
      90% of studies. After initiation of ECLS, studies reported median [interquartile
      range (IQR)] reductions in: tidal volume [2.4 mL/kg PBW (2.2-2.9)], plateau
      pressure [4.3 cmH2O (3.5-5.8)], positive end-expiratory pressure (PEEP) [0.20
      cmH2O (0-3.0)], and FiO2 [0.40 (0.30-0.60)]. Median (IQR) overall mortality was
      41 % (31-51%). CONCLUSIONS: Reduction in the intensity of mechanical ventilation
      in patients with ARDS supported by ECLS is common, suggesting that clinicians may
      be focused on reducing VILI after ECLS initiation. Future investigations should
      focus on establishing the optimal ventilatory strategy for patients with ARDS who
      require ECLS.

PMID- 25752304
TI  - Is gentamicin affecting the neuromuscular system of critically ill patients?

PMID- 25752306
TI  - Do we need an alternative 'relational approach' to saviour siblings?

PMID- 25752307
TI  - Goserelin reduces ovarian failure associated with breast cancer chemotherapy,
      study shows.

PMID- 25752308
TI  - Acute Kidney Injury in the Critically Ill Patient: A Current Review of the
      Literature.
AB  - PURPOSE: A comprehensive review of the literature to provide a focused and
      thorough update on the issue of acute kidney injury (AKI) in the surgical
      patient. METHODS: A PubMed and Medline search was performed and keywords included
      AKI, renal failure, critically ill, and renal replacement therapy (RRT).
      PRINCIPAL FINDINGS: A common clinical problem encountered in critically ill
      patients is AKI. The recent consensus definitions for the diagnosis and
      classification of AKI (ie, Risk, Injury, Failure, Loss of kidney function, and
      End-stage kidney disease/Acute Kidney Injury Network) have enabled us to
      standardize the severity of AKI and facilitate strategies for prevention. These
      strategies as well as treatment modalities of AKI are discussed. We provide a
      concise overview of the issue of renal failure. We describe strategies for
      prevention including types of fluids used for resuscitation, timing of initiation
      of RRT, and different treatment modalities currently available for clinical
      practice. CONCLUSIONS: Acute kidney injury is a common problem in the critically
      ill patient and is associated with worse clinical outcomes. A standardized
      definition and staging system has led to improved diagnosis and understanding of
      the pathophysiology of AKI. There are many trials leading to improved prevention
      and management of the disease.

PMID- 25752305
TI  - In vivo evaluation of the dentate gate theory in epilepsy.
AB  - The dentate gyrus is a region subject to intense study in epilepsy because of its
      posited role as a 'gate', acting to inhibit overexcitation in the hippocampal
      circuitry through its unique synaptic, cellular and network properties that
      result in relatively low excitability. Numerous changes predicted to produce
      dentate hyperexcitability are seen in epileptic patients and animal models.
      However, recent findings question whether changes are causative or reactive, as
      well as the pathophysiological relevance of the dentate in epilepsy. Critically,
      direct in vivo modulation of dentate 'gate' function during spontaneous seizure
      activity has not been explored. Therefore, using a mouse model of temporal lobe
      epilepsy with hippocampal sclerosis, a closed-loop system and selective
      optogenetic manipulation of granule cells during seizures, we directly tested the
      dentate 'gate' hypothesis in vivo. Consistent with the dentate gate theory,
      optogenetic gate restoration through granule cell hyperpolarization efficiently
      stopped spontaneous seizures. By contrast, optogenetic activation of granule
      cells exacerbated spontaneous seizures. Furthermore, activating granule cells in
      non-epileptic animals evoked acute seizures of increasing severity. These data
      indicate that the dentate gyrus is a critical node in the temporal lobe seizure
      network, and provide the first in vivo support for the dentate 'gate' hypothesis.

PMID- 25752309
TI  - Synergistic and drug-resistant reversing effects of diorcinol D combined with
      fluconazole against Candida albicans.
AB  - The emergence of drug resistance and limitation of antifungal agents bring
      enormous challenges to the management of Candida infection. Combination therapy
      is a useful way to treat the fungal infection, especially for those difficult-to
      treat infections. In this research, we investigated the interaction effects
      between diorcinol D (DD), an antifungal active natural product from lichen
      endophytic fungus and fluconazole (FLC) against planktonic cells and mature
      biofilms of Candida albicans in vitro by checkerboard microdilution and time
      killing tests. Both fractional inhibitory concentration index model and DeltaE
      model revealed a synergistic antifungal action between DD and FLC against all
      five azole-resistant isolates and synergistic or indifferent effects for other
      five azole-sensitive isolates. In addition, the synergies were obtained from
      eradicating C. albicans mature biofilms tests using two wild-type strains (SC5314
      and YEM30), an azole-resistant isolate 28I and an azole-sensitive isolate 18B.
      The time-killing tests also showed synergistic fungicidal action between DD and
      FLC. Mechanism test revealed that DD inhibited the activity of efflux pump and
      retarded the biosynthesis of ergosterol, which probably contributed to the
      synergetic action as well as the reversing activity of drug resistance. 

PMID- 25752310
TI  - Perineal care.
AB  - INTRODUCTION: More than 85% of women having a vaginal birth suffer some perineal
      trauma. Spontaneous tears requiring suturing are estimated to occur in at least
      one third of women in the UK and US. Perineal trauma can lead to long-term
      physical and psychological problems. METHODS AND OUTCOMES: We conducted a
      systematic review and aimed to answer the following clinical questions: What are
      the effects of different methods and materials for primary repair of first- and
      second-degree tears and episiotomies? What are the effects of different methods
      and materials for primary repair of obstetric anal sphincter injuries (third- and
      fourth-degree tears)? We searched: Medline, Embase, The Cochrane Library, and
      other important databases up to November 2013 (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 33 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:
      conventional suturing; different methods and materials for primary repair of
      obstetric anal sphincter injuries; non-suturing of muscle and skin (or perineal
      skin alone); and sutures (absorbable synthetic sutures, catgut sutures,
      continuous sutures, interrupted sutures).

PMID- 25752311
TI  - It's not just the joints, it's the whole thing: qualitative analysis of patients'
      experience of flare in psoriatic arthritis.
AB  - OBJECTIVE: Flare is a commonly used term in arthritis, including PsA, but remains
      undefined. This study seeks to explore patients' experience of flare. METHODS:
      Eighteen semi-structured interviews were undertaken with patients with PsA in an
      informal clinical setting. Patients were purposively sampled from specialist
      clinic lists to reflect the major elements of the psoriatic disease spectrum.
      Approximately one-third of patients reported themselves to be in a flare state at
      the time of the interview. Transcripts underwent thematic analysis according to
      the recommendations of Braun and Clarke (Using thematic analysis in psychology.
      Qual Res Psychol 2006;3:77-101). NVivo software was utilized, with initial coding
      reflecting the source data, such as pain, feeling miserable and feeling slowed
      down. Codes were then grouped into associated clusters. These clusters and the
      interrelationships were then summarized into emergent themes. RESULTS: The mean
      age of the patients was 44 years, and patients' average disease duration was 4.5
      years. Nine main overarching themes pertaining to flare were identified: physical
      symptoms, social withdrawal, psychological symptoms, fatigue, loss of normal
      function, triggers, management of pre-flare, management of flare and timing.
      These show some degree of overlap and are interlinked, with some degree of
      temporality emerging as related to patients' experience of flare. CONCLUSION:
      This study has identified a number of components of flare in PsA from the patient
      perspective. Although the emergent themes are of an overlapping and interactive
      nature, it is clear that flare in PsA is more than a swollen or tender joint
      count as measured in clinical practice.

PMID- 25752312
TI  - Prediction and impact of attacks of Raynaud's phenomenon, as judged by patient
      perception.
AB  - OBJECTIVE: To evaluate whether patients can predict attacks of RP (if so, this
      would have implications for developing new treatments) and to evaluate the impact
      of RP attacks on quality of life (QoL). METHODS: Individuals with RP were invited
      through international patient associations to participate in an online survey.
      RESULTS: Responses from 443 subjects with self-reported RP from 15 countries were
      evaluable. The mean age of subjects was 41 years (91% female). Fifty-eight per
      cent of subjects reported they could predict at least 51% of RP attacks, and 57%
      could predict attack severity either fairly well or better [with 43% predicting
      severity only poorly (30%) or very poorly (13%)]. Sixty-four per cent of subjects
      reported a poor or very poor current ability to prevent/control RP attacks. One
      hundred and eighty-two subjects (41%) reported current or previous use of
      medications for RP: 82% reported at least one currently used medication being
      tolerated, but only 16% reported at least one current medication being effective.
      Most subjects (78%) reported making at least one life adjustment due to RP, with
      more in subjects with secondary RP compared with primary RP (87% vs 71%, P =
      0.001). Current QoL with RP was impaired [mean = 6/10 (10 best imaginable)] and
      secondary RP subjects reported a greater absolute improvement when asked to
      imagine their QoL without RP (2.3 vs 3.3 P = 0.0002). CONCLUSION: Subjects'
      ability to predict RP attacks is limited. Treatments were generally considered
      tolerable but seldom fully effective. Our results confirm an unmet need for new
      treatments. RP significantly impacts on QoL in all subjects.

PMID- 25752313
TI  - The Influence of Gaze Control on Visual Perception: Eye Movements and Visual
      Stability.
AB  - Primates make several saccadic eye movements each second, and yet the retinal
      motion these movements generate goes unnoticed. Saccadic suppression is a
      profound loss of visual sensitivity occurring around the time of eye movements,
      and it is thought to contribute to visual stability by blunting the perception of
      self-generated motion. Neurophysiological studies have produced evidence that
      neurons throughout the visual system, including both the dorsal and ventral
      streams of extrastriate visual cortex, show a reduction in visual responses or
      sensitivity around the time of saccades. However, the source of this suppression
      remains unknown. We review evidence that oculomotor regions such as the superior
      colliculus and frontal eye field may play a role, as well as anatomical data that
      place constraints on possible mechanisms of suppression. 

PMID- 25752315
TI  - Measures of atherosclerotic burden are associated with clinically manifest
      cardiovascular disease in type 2 diabetes: a European cross-sectional study.
AB  - BACKGROUND: There is a need to develop and validate surrogate markers of
      cardiovascular disease (CVD) in subjects with diabetes. The macrovascular changes
      associated with diabetes include aggravated atherosclerosis, increased arterial
      stiffness and endothelial dysfunction. The aim of this study was to determine
      which of these factors is most strongly associated with clinically manifest
      cardiovascular events. METHODS: Vascular changes were measured in a cohort of 458
      subjects with type 2 diabetes (T2D) and CVD (myocardial infarction, stroke or
      lower extremity arterial disease), 527 subjects with T2D but without clinically
      manifest CVD and 515 subjects without T2D and with or without CVD. RESULTS:
      Carotid intima-media thickness (IMT) and ankle-brachial pressure index were
      independently associated with the presence of CVD in subjects with T2D, whereas
      pulse wave velocity and endothelial function provided limited independent
      additive information. Measurement of IMT in the carotid bulb provided better
      discrimination of the presence of CVD in subjects with T2D than measurement of
      IMT in the common carotid artery. The factors most significantly associated with
      increased carotid IMT in T2D were age, disease duration, systolic blood pressure,
      impaired renal function and increased arterial stiffness, whereas there were no
      or weak independent associations with metabolic factors and endothelial
      dysfunction. CONCLUSIONS: Measures of atherosclerotic burden are associated with
      clinically manifest CVD in subjects with T2D. In addition, vascular changes that
      are not directly related to known metabolic risk factors are important in the
      development of both atherosclerosis and CVD in T2D. A better understanding of the
      mechanisms involved is crucial for enabling better identification of CVD risk in
      T2D.

PMID- 25752314
TI  - Emergence of Cognition from Action.
AB  - Theories of brain function have evolved through multiple stages. The first
      proposition was that brain networks support a set of reflex responses, with
      current sensory inputs producing immediate motor outputs. The behaviorist
      paradigm suggested that actions can always be explained as a response to
      immediate external cues. In response to these views, the cognitive paradigm
      argued that behavior cannot be understood simply as input-output functions
      because the hidden layers of brain generate unpredictability. The central
      processing was termed "cognition." Here we propose a neuroscience-based model of
      cognition. Our core hypothesis is that cognition depends on internal models of
      the animal and its world, where internally generated sequences can serve to
      perform "what if" scenarios and anticipate the possible consequences of
      alternative actions without actually testing them, and aid in the decisions of
      overt actions. We support our hypotheses by several examples of recent
      experimental findings and show how externally guided cell assembly sequences
      become internalized to support cognitive functions. 

PMID- 25752316
TI  - Chromatin dynamics of plant telomeres and ribosomal genes.
AB  - Telomeres and genes encoding 45S ribosomal RNA (rDNA) are frequently located
      adjacent to each other on eukaryotic chromosomes. Although their primary roles
      are different, they show striking similarities with respect to their features and
      additional functions. Both genome domains have remarkably dynamic chromatin
      structures. Both are hypersensitive to dysfunctional histone chaperones,
      responding at the genomic and epigenomic levels. Both generate non-coding
      transcripts that, in addition to their epigenetic roles, may induce gross
      chromosomal rearrangements. Both give rise to chromosomal fragile sites, as their
      replication is intrinsically problematic. However, at the same time, both are
      essential for maintenance of genomic stability and integrity. Here we discuss the
      structural and functional inter-connectivity of telomeres and rDNA, with a focus
      on recent results obtained in plants. 

PMID- 25752317
TI  - Cladosporium cladosporioides: a so far unidentified cause of white piedra.

PMID- 25752318
TI  - Perianal lichen dermatoses: A review of 60 cases.
AB  - OBJECTIVES: To determine the diagnostic range of lichen dermatoses of the
      perianus, their extent, and response to treatment. METHODS: We reviewed perianal
      biopsies submitted to a tertiary referral pathology service between January 2010
      and July 2014, interpreted as 'lichen' or 'lichenoid'. We collected data on
      patients' characteristics, referring specialty, extent of lesion and response to
      treatment. RESULTS: During the study period, 60 perianal biopsies met our
      inclusion criteria. The distribution of diagnoses was lichen sclerosus (LS) in
      25/60 (42%), lichen simplex chronicus (LSC) in 23/60 (38%), lichen planus (LP) in
      10/60 (17%), and a non-specific lichenoid reaction in 2/60 (3%). Eleven of 25
      cases of LS (44%) showed superimposed LSC. Of 10 LP cases, nine (90%) were
      hypertrophic and three of these showed pseudoepitheliomatous hyperplasia; none
      were erosive LP. Compared with patients in the LS and LSC groups, those with LP
      were more likely to have a localised lesion. Topical steroids were prescribed in
      91% cases with treatment data available, and 98% of treated patients who returned
      for follow up had improved or their disease was resolved. CONCLUSIONS: We
      encountered a spectrum of perianal lichen dermatoses, with LS, LP and LSC all
      represented. LS biopsied at the perianus is often lichenified. Hypertrophic LP is
      a common form of LP at the perianus.

PMID- 25752319
TI  - Body composition, pre-diabetes and cardiovascular disease risk in early
      schizophrenia.
AB  - AIM: This preliminary study examines the relationship between body composition,
      insulin resistance and NCEP-III-defined cardiovascular disease risk factors in
      persons early in the course of schizophrenia exposed to commonly prescribed
      atypical antipsychotic medications. METHODS: Subjects underwent modified oral
      glucose tolerance tests (OGTTs) and DEXA (dual X-ray absorptiometry) scans
      corrected for relevant sociodemographic data, including activity levels. We used
      linear multiple regression models to evaluate relationships between body
      composition and metabolic variables. RESULTS: Thirty-six individuals diagnosed
      with schizophrenia, receiving atypical antipsychotic monotherapy, and within 5
      years of illness onset, participated. Average age was 25.1 +/- 3.6 years (range,
      19-34) and duration of illness was 2.5 years (30 +/- 18 months). Mean body mass
      index (BMI) was 28.3 +/- 4.9, with a mean total body fat mass of 28.6 +/- 8.4%,
      suggesting an increase in fat relative to BMI. Ten participants (28%) had pre
      diabetes (fasting glucose 100-126 mg dL-1 or 2-h OGTT 140-200 mg dL-1 ), but no
      participant had diabetes. Insulin resistance (HOMA-IR) was predicted by total
      body mass (BMI) more so than by body fat mass, with an incremental contribution
      derived from antipsychotics. Insulin secretion in response to glucose challenge
      was predicted by BMI, body fat mass and antipsychotic medication. CONCLUSIONS:
      Fat mass relative to BMI was increased in early schizophrenia patients receiving
      atypical antipsychotics. Body composition accounted for most of the variance in
      risk for abnormalities in glucose metabolism. Incremental contributions were
      derived from atypical antipsychotics, in line with their known adipogenicity. If
      direct fat mass measures are unavailable, frequent BMI measures may be practical
      proxy markers for metabolic risk.

PMID- 25752320
TI  - Supraspinal actions of nociceptin/orphanin FQ, morphine and substance P in
      regulating pain and itch in non-human primates.
AB  - BACKGROUND AND PURPOSE: Nociceptin/orphanin FQ (N/OFQ) peptide (NOP) receptor
      agonists display a promising analgesic profile in preclinical studies. However,
      supraspinal N/OFQ produced hyperalgesia in rodents and such effects have not been
      addressed in primates. Thus, the aim of this study was to investigate the effects
      of centrally administered ligands on regulating pain and itch in non-human
      primates. In particular, nociceptive thresholds affected by intracisternal N/OFQ
      were compared with those of morphine and substance P, known to provide analgesia
      and mediate hyperalgesia, respectively, in humans. EXPERIMENTAL APPROACH:
      Intrathecal catheters were installed to allow intracisternal and lumbar
      intrathecal administration in awake and unanaesthetized rhesus monkeys.
      Nociceptive responses were measured using the warm water tail-withdrawal assay.
      Itch scratching responses were scored from videotapes recording behavioural
      activities of monkeys in their home cages. Antagonist studies were conducted to
      validate the receptor mechanisms underlying intracisternally elicited behavioural
      responses. KEY RESULTS: Intracisternal morphine (100 nmol) elicited more head
      scratches than those after intrathecal morphine. Distinct dermatomal scratching
      locations between the two routes suggest a corresponding activation of
      supraspinal and spinal MU receptors. Unlike intracisternal substance P, which
      induced hyperalgesia, intracisternal N/OFQ (100 nmol) produced antinociceptive
      effects mediated by NOP receptors. Neither peptide increased scratching
      responses. CONCLUSIONS AND IMPLICATIONS: Taken together, these results
      demonstrated differential actions of ligands in the primate supraspinal region in
      regulating pain and itch. This study not only improves scientific understanding
      of the N/OFQ-NOP receptor system in pain processing but also supports the
      therapeutic potential of NOP-related ligands as analgesics.

PMID- 25752321
TI  - Nodule excitability in an animal model of periventricular nodular heterotopia: c
      fos activation in organotypic hippocampal slices.
AB  - OBJECTIVE: Aberrations in brain development may lead to dysplastic structures
      such as periventricular nodules. Although these abnormal collections of neurons
      are often associated with difficult-to-control seizure activity, there is little
      consensus regarding the epileptogenicity of the nodules themselves. Because one
      common treatment option is surgical resection of suspected epileptic nodules, it
      is important to determine whether these structures in fact give rise, or
      essentially contribute, to epileptic activities. METHODS: To study the
      excitability of aberrant nodules, we have examined c-fos activation in
      organotypic hippocampal slice cultures generated from an animal model of
      periventricular nodular heterotopia created by treating pregnant rats with
      methylazoxymethanol acetate. Using this preparation, we have also attempted to
      assess tissue excitability when the nodule is surgically removed from the
      culture. We then compared c-fos activation in this in vitro preparation to c-fos
      activation generated in an intact rat treated with kainic acid. RESULTS:
      Quantitative analysis of c-fos activation failed to show enhanced nodule
      excitability compared to neocortex or CA1 hippocampus. However, when we compared
      cultures with and without a nodule, presence of a nodule did affect the
      excitability of CA1 and cortex, at least as reflected in c-fos labeling. Surgical
      removal of the nodule did not result in a consistent decrease in excitability as
      reflected in the c-fos biomarker. SIGNIFICANCE: Our results from the organotypic
      culture were generally consistent with our observations on excitability in the
      intact rat-as seen not only with c-fos but also in previous electrophysiologic
      studies. At least in this model, the nodule does not appear to be responsible for
      enhanced excitability (or, presumably, seizure initiation). Excitability is
      different in tissue that contains a nodule, suggesting altered network function,
      perhaps reflecting the abnormal developmental pattern that gave rise to the
      nodule.

PMID- 25752322
TI  - Governing sexual behaviour through humanitarian codes of conduct.
AB  - Since 2001, there has been a growing consensus that sexual exploitation and abuse
      of intended beneficiaries by humanitarian workers is a real and widespread
      problem that requires governance. Codes of conduct have been promoted as a key
      mechanism for governing the sexual behaviour of humanitarian workers and,
      ultimately, preventing sexual exploitation and abuse (PSEA). This article
      presents a systematic study of PSEA codes of conduct adopted by humanitarian non
      governmental organisations (NGOs) and how they govern the sexual behaviour of
      humanitarian workers. It draws on Foucault's analytics of governance and speech
      act theory to examine the findings of a survey of references to codes of conduct
      made on the websites of 100 humanitarian NGOs, and to analyse some features of
      the organisation-specific PSEA codes identified. 

PMID- 25752323
TI  - A novel HLA-A*32 allele, A*32:67 was identified by polymerase chain reaction
      sequence-based typing in a Chinese individual.
AB  - HLA-A*32:67 has a single nucleotide difference at position 286 C>A compared with
      HLA-A*32:01:01. 

PMID- 25752324
TI  - Evaluation of body growth and immunity-related differentially expressed genes
      through deep RNA sequencing in the piglets of Jeju native pig and Berkshire.
AB  - This study was carried out with the objective to investigate the differentially
      expressed genes (DEGs) between Jeju native pig (JNP) and Berkshire piglets. The
      RNA-Seq technique was used to investigate the transcriptomes in the fat, liver
      and longissimus dorsi muscle from these two breeds. Paired-end reads of the
      sequences that passed the quality filters were aligned to the Sus scrofa genome
      using tophat2 (v2.0.2). In this study, 65% of muscle, 20% of fat and 54% of liver
      genes showed higher expression in the piglets of JNP than in Berkshire. Gene
      Ontology and signaling pathways showed that immune response and lipid metabolisms
      were commonly enriched pathways in all three tissues. It was found that the genes
      pertaining to body growth and immune system are significantly (P < 0.01) more
      highly expressed in Berkshire piglets. DEGs explored between the piglets of the
      two breeds might influence the identification of the genetic markers for further
      breed improvement programs. Our findings provide a new perspective for
      understanding and identifying candidate genes that are involved in various
      biological functions. Moreover, transcriptome analysis makes it easier to
      understand the differences between genetic mechanisms of breeds.

PMID- 25752325
TI  - The role of BRAF mutations in primary melanoma growth rate and survival.
AB  - BACKGROUND: The clinical behaviour and prognosis of primary melanomas harbouring
      BRAF mutations is not fully understood. OBJECTIVES: To investigate the effect of
      mutation status on primary melanoma growth rate and melanoma-specific survival
      (MSS). METHODS: A prospective cohort of 196 patients with stage I-III primary
      cutaneous melanoma were followed for a median of 92 months, pre-dating the
      institution of BRAF inhibitor therapy. Clinicopathological variables were
      correlated with mutation status and hazard ratios (HRs) estimated for MSS.
      RESULTS: Of 196 tumours, 77 (39.2%) were BRAF V600E, 10 (5.1%) BRAF V600K and 33
      (16.8%) were NRAS mutant. BRAF V600E mutant melanomas were associated with
      favourable clinical characteristics and tended to be slower growing compared with
      BRAF V600K, NRAS mutant or BRAF/NRAS wild-type tumours (0.12 mm per month, 0.61
      mm per month, 0.36 mm per month and 0.23 mm per month, respectively; P = 0.05).
      There were 39 melanoma deaths, and BRAF mutant melanomas were associated with
      poorer MSS in stage I-III disease [HR 2.60, 95% confidence interval (CI) 1.20
      5.63; P = 0.02] and stage I-II disease (HR 3.39, 95% CI 1.12-10.22; P = 0.03)
      after adjusting for other prognostic variables. Considered separately, BRAF V600E
      mutant melanomas were strongly associated with MSS independently of thickness and
      nodal status (HR 3.89, 95% CI 1.67-9.09; P < 0.01) but BRAF V600K mutant tumours
      were not (HR 1.19, 95% CI 0.36-3.92; P = 0.77). CONCLUSIONS: The presence of a
      BRAF mutation does not necessarily 'drive' more rapid tumour growth but is
      associated with poorer MSS in patients with early-stage disease.

PMID- 25752326
TI  - Phenotype-dependent inhibition of glutamatergic transmission on nucleus accumbens
      medium spiny neurons by the abused inhalant toluene.
AB  - Abused inhalants are voluntarily inhaled at high concentrations to produce
      intoxicating effects. Results from animal studies show that the abused inhalant
      toluene triggers behaviors, such as self-administration and conditioned place
      preference, which are commonly associated with addictive drugs. However, little
      is known about how toluene affects neurons within the nucleus accumbens (NAc), a
      brain region within the basal ganglia that mediates goal-directed behaviors and
      is implicated in the development and maintenance of addictive behaviors. Here we
      report that toluene inhibits a component of the after-hyperpolarization
      potential, and dose-dependently inhibits N-methyl-D-aspartate (NMDA)-mediated
      currents in rat NAc medium spiny neurons (MSN). Moreover, using the multivariate
      statistical technique, partial least squares discriminative analysis to analyze
      electrophysiological measures from rat NAc MSNs, we show that toluene induces a
      persistent depression of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid
      (AMPA)-mediated currents in one subtype of NAc MSNs, and that the
      electrophysiological features of MSN neurons predicts their sensitivity to
      toluene. The CB1 receptor antagonist AM281 blocked the toluene-induced long-term
      depression of AMPA currents, indicating that this process is dependent on
      endocannabinoid signaling. The neuronal identity of recorded cells was examined
      using dual histochemistry and shows that toluene-sensitive NAc neurons are
      dopamine D2 MSNs that express preproenkephalin mRNA. Overall, the results from
      these studies indicate that physiological characteristics obtained from NAc MSNs
      during whole-cell patch-clamp recordings reliably predict neuronal phenotype, and
      that the abused inhalant toluene differentially depresses excitatory
      neurotransmission in NAc neuronal subtypes. 

PMID- 25752327
TI  - Global patterns of hepatocellular carcinoma management from diagnosis to death:
      the BRIDGE Study.
AB  - BACKGROUND & AIMS: Hepatocellular carcinoma (HCC) is the second most common cause
      of cancer deaths worldwide. The global HCC BRIDGE study was a multiregional,
      large-scale, longitudinal cohort study undertaken to improve understanding of
      real-life management of patients with HCC, from diagnosis to death. METHODS: Data
      were collected retrospectively from January 2005 to September 2012 by chart
      reviews of eligible patients newly diagnosed with HCC at participating
      institutions. RESULTS: Forty-two sites in 14 countries contributed final data for
      18 031 patients. Asia accounted for 67% of patients, Europe for 20% and North
      America for 13%. As expected, the most common risk factor was hepatitis C virus
      in North America, Europe and Japan, and hepatitis B virus in China, South Korea
      and Taiwan. The most common Barcelona Clinic Liver Cancer stage at diagnosis was
      C in North America, Europe, China and South Korea, and A in Taiwan and Japan.
      Across all stages, first HCC treatment was most frequently transarterial
      chemoembolization in North America, Europe, China and South Korea, percutaneous
      ethanol injection or radiofrequency ablation in Japan and resection in Taiwan.
      Survival from first HCC treatment varied significantly by region, with median
      overall survival not reached for Taiwan and 60, 33, 31, 24 and 23 months for
      Japan, North America, South Korea, Europe and China respectively (P < 0.0001).
      CONCLUSIONS: Initial results from the BRIDGE study confirm previously reported
      regional trends in patient demographic characteristics and HCC risk factors,
      document the heterogeneity of treatment approaches across regions/countries and
      underscore the need for earlier HCC diagnosis worldwide.

PMID- 25752328
TI  - Topical simvastatin promotes healing of Staphylococcus aureus-contaminated
      cutaneous wounds.
AB  - Cutaneous wounds are prompt to be contaminated by bacteria, but the clinical
      benefits of applying antibiotics and antiseptics in wound management have not
      been proven. Statins are 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA)
      reductase inhibitors commonly used to lower cholesterol levels. Studies indicated
      that statins, especially simvastatin, promote wound healing in experimental
      models. As Staphylococcus aureus is one of the most important microorganism
      responsible for wound infections, the aims of this study were to characterise the
      anti-staphylococcal activity of simvastatin and to evaluate the application of
      simvastatin as a topical therapy for S. aureus-contaminated wounds. In the
      present study, simvastatin was bacteriostatic against S. aureus at sub-inhibitory
      concentrations up to 8 hours after exposure. Further increased concentrations of
      simvastatin above the minimal inhibitory concentration (MIC) did not enhance the
      growth inhibitory effect. By contrast, the ability of simvastatin to inhibit S.
      aureus biofilm formation was concentration dependent. Topical application of
      simvastatin at its MIC against S. aureus accelerated the healing and bacterial
      clearance of S. aureus-contaminated wounds in an excisional mice wound model.
      This effective concentration is well below the safe concentration for topical
      use. Collectively, topical application of simvastatin has the potential as a
      novel modality for managing wound infections and promoting wound healing.

PMID- 25752330
TI  - Biopsychosocial contributions to sex differences in pain.

PMID- 25752331
TI  - In vivo ocular imaging of the cornea of the normal female laboratory beagle using
      confocal microscopy.
AB  - OBJECTIVE: To obtain normative data for the normal laboratory beagle cornea using
      high-resolution in vivo confocal microscopy (IVCM). ANIMALS STUDIED: Sixteen eyes
      of eight healthy young female intact beagles. PROCEDURES: The central cornea was
      imaged using IVCM. Mixed effects linear regression was used for statistical
      analysis. RESULTS: in vivo confocal microscopy allowed detailed visualization and
      quantification of epithelial cells (superficial epithelial cell diameter: 43.25
      +/- 6.64 MUm, basal cell diameter: 4.43 +/- 0.67 MUm), and nerve fibers
      (subepithelial nerve fiber diameter: 2.38 +/- 0.69 MUm, anterior stromal nerve
      fiber diameter: 16.93 +/- 4.55 MUm). Keratocyte density (anterior stroma 993.38
      +/- 134.24 cells/mm(2) , posterior stroma 789.38 +/- 87.13 cells/mm(2) ) and
      endothelial cell density (2815.18 +/- 212.59 cells/mm(2) ) were also measured.
      CONCLUSION: High-resolution IVCM provides detailed noninvasive evaluation of the
      cornea in the normal laboratory beagle.

PMID- 25752332
TI  - Molecular and phenotypic characterization of Agrobacterium species from vineyards
      allows identification of typical Agrobacterium vitis and atypical biovar 1
      strains.
AB  - AIM: To molecularly and phenotypically characterize a selection of Agrobacterium
      like isolates from grapevine canes, crowns, soil and tumours in plants grown
      under cold conditions. METHODS AND RESULTS: Most of the strains were biovar 3
      (Agrobacterium vitis), and the remaining were atypical biovar 1 (Agrobacterium
      tumefaciens). All of them were tumourigenic on grapevine plants but differences
      in other hosts were observed. Chromosomal and plasmid-borne traits were analysed
      by gene amplification with four primer sets. Detection of the pectin enzyme
      hydrolase gene clearly distinguished A. vitis from the atypical A. tumefaciens.
      Regarding the virulence sensor gene, limited host range tumour-inducing plasmids
      were found in the atypical isolates. About opine utilization, most A. vitis and
      some A. tumefaciens contained octopine/cucumopine plasmids, but the nopaline-type
      was only detected in one A. tumefaciens. CONCLUSIONS: The A. vitis strains were
      molecularly and phenotypically more homogeneous than those of A. tumefaciens, the
      latter displaying some typical A. vitis characteristics, suggesting an adaptation
      to life in grapevine. SIGNIFICANCE AND IMPACT OF THE STUDY: The findings of this
      work will help to improve detection procedures of the pathogen, and demonstrate
      the pathogen diversity in cold vineyards, laying the groundwork for
      epidemiological studies and development of control strategies of the crown and
      cane gall disease.

PMID- 25752333
TI  - Becoming an adult: A proposed typology of adult status based on a study of
      Spanish youths.
AB  - Emerging adulthood is a transitional period which has been examined in relatively
      few studies in Southern European countries. This study has two aims: (1) to
      determine the features of emerging adulthood in Spain based on criteria for
      adulthood and experiential dimensions; and (2) to explore whether variations in
      these criteria are related to gender and adult status (self-classification as an
      adult and adult role adoption). Participants included 347 young Spanish people,
      aged 18-30, who completed a questionnaire about their conceptions of adulthood.
      They used similar criteria for adulthood to other Western countries, placing an
      extremely strong emphasis on psychological maturity criteria in comparison with
      role transition indicators. Important variations were observed in both the
      importance and achievement of criteria for adulthood according to gender and
      adult status. The results likewise suggest there may be different psychosocial
      profiles associated with each adult status group. The relevance of this
      classification to future research in the field of emerging adulthood is
      discussed. 

PMID- 25752335
TI  - Isolated oculomotor nerve palsy revealing infectious mononucleosis.

PMID- 25752334
TI  - Do Experiences with Medicare Managed Care Vary According to the Proportion of
      Same-Race/Ethnicity/Language Individuals Enrolled in One's Contract?
AB  - OBJECTIVE: To examine whether care experiences and immunization for
      racial/ethnic/language minority Medicare beneficiaries vary with the proportion
      of same-group beneficiaries in Medicare Advantage (MA) contracts. DATA
      SOURCES/STUDY SETTING: Exactly 492,495 Medicare beneficiaries responding to the
      2008-2009 MA Consumer Assessment of Healthcare Providers and Systems (CAHPS)
      Survey. DATA COLLECTION/EXTRACTION METHODS: Mixed-effect regression models
      predicted eight CAHPS patient experience measures from self-reported
      race/ethnicity/language preference at individual and contract levels, beneficiary
      level case-mix adjustors, along with contract and geographic random effects.
      PRINCIPAL FINDINGS: As a contract's proportion of a given minority group
      increased, overall and non-Hispanic, white patient experiences were poorer on
      average; for the minority group in question, however, high-minority plans may
      score as well as low-minority plans. Spanish-preferring Hispanic beneficiaries
      also experience smaller disparities relative to non-Hispanic whites in plans with
      higher Spanish-preferring proportions. CONCLUSIONS: The tendency for high
      minority contracts to provide less positive patient experiences for others in the
      contract, but similar or even more positive patient experiences for concentrated
      minority group beneficiaries, may reflect cultural competency, particularly
      language services, that partially or fully counterbalance the poorer overall
      quality of these contracts. For some beneficiaries, experiences may be just as
      positive in some high-minority plans with low overall scores as in plans with
      higher overall scores.

PMID- 25752336
TI  - Reduction of protein kinase C alpha (PKC-alpha) promote apoptosis via down
      regulation of Dicer in bladder cancer.
AB  - In clinic, we examined the expression of protein kinase C (PKC)-alpha and Dicer
      in the samples of bladder cancer patients, and found that the two proteins have a
      line correlation. Our study confirmed this correlation existing by clearing the
      decreasing expression of Dicer after the PKC-alpha knockdown. Treatment of
      bladder cancer cell lines (T24, 5637) with the PKC-alpha or Dicer knockdown and
      the PKC inhibitors (Calphostin C and Go 6976) can promote the apoptosis.
      Inhibition of PKC can increase the activities of caspase-3 and PARP, however,
      decrease the expression of Dicer. And knockdown of the PKC-alpha or Dicer can
      also activate the caspase-3 or the PARP. Considering the reduction of PKC-alpha
      can induce the Dicer down-regulation, we make the conclusion that the reduction
      of PKC-alpha can promote the apoptosis via the down-regulation of Dicer in
      bladder cancer. 

PMID- 25752337
TI  - Association between comorbidity burden and rapid cognitive decline in individuals
      with mild to moderate Alzheimer's disease.
AB  - OBJECTIVES: To determine the association between rapid cognitive decline and
      burden of comorbidities as assessed using the Charlson Comorbidity Index in
      individuals aged 65 and older with Alzheimer's disease (AD). DESIGN:
      Retrospective cohort study. SETTING: Memory clinic at the University Hospital of
      Nantes. PARTICIPANTS: Individuals aged 65 and older with AD (n=170).
      MEASUREMENTS: Subjects were followed for 1 year. Rapid cognitive decline was
      defined as a decrease of 3 or more points on the Mini-Mental State Examination
      per 12-month period. Variables studied were the Charlson Comorbidity Index
      (measure of comorbidity burden), age, sex, AD stage, type of residence (living at
      home or not), presence of caregiver, functional abilities (Lawton and Katz
      scales), risk of malnutrition or depression, and intercurrent events
      (hospitalization or initiating home care). RESULTS: Rapid cognitive decline at 1
      year follow-up occurred in 65 subjects (38.2%). In fully adjusted logistic
      regression analysis, Charlson Comorbidity Index was significantly associated with
      rapid cognitive decline (odds ratio (OR)=1.30, P=.03). Moderate stage of AD
      (OR=2.07, P=.04) and living at home (OR=4.17, P=.04) were also associated with
      rapid cognitive decline. CONCLUSION: Comorbidity burden was associated with rapid
      cognitive decline in subjects with AD.

PMID- 25752329
TI  - Is the adiposity-associated FTO gene variant related to all-cause mortality
      independent of adiposity? Meta-analysis of data from 169,551 Caucasian adults.
AB  - Previously, a single nucleotide polymorphism (SNP), rs9939609, in the FTO gene
      showed a much stronger association with all-cause mortality than expected from
      its association with body mass index (BMI), body fat mass index (FMI) and waist
      circumference (WC). This finding implies that the SNP has strong pleiotropic
      effects on adiposity and adiposity-independent pathological pathways that leads
      to increased mortality. To investigate this further, we conducted a meta-analysis
      of similar data from 34 longitudinal studies including 169,551 adult Caucasians
      among whom 27,100 died during follow-up. Linear regression showed that the minor
      allele of the FTO SNP was associated with greater BMI (n = 169,551; 0.32 kg m(-2)
      ; 95% CI 0.28-0.32, P < 1 * 10(-32) ), WC (n = 152,631; 0.76 cm; 0.68-0.84, P < 1
      * 10(-32) ) and FMI (n = 48,192; 0.17 kg m(-2) ; 0.13-0.22, P = 1.0 * 10(-13) ).
      Cox proportional hazard regression analyses for mortality showed that the hazards
      ratio (HR) for the minor allele of the FTO SNPs was 1.02 (1.00-1.04, P = 0.097),
      but the apparent excess risk was eliminated after adjustment for BMI and WC (HR:
      1.00; 0.98-1.03, P = 0.662) and for FMI (HR: 1.00; 0.96-1.04, P = 0.932). In
      conclusion, this study does not support that the FTO SNP is associated with all
      cause mortality independently of the adiposity phenotypes. 

PMID- 25752339
TI  - Melatonin attenuates methamphetamine-induced inhibition of proliferation of adult
      rat hippocampal progenitor cells in vitro.
AB  - Methamphetamine (METH) is an extremely addictive stimulatory drug. A recent study
      suggested that METH may cause an impairment in the proliferation of hippocampal
      neural progenitor cells, but the underlying mechanism of this effect remains
      unknown. Blood and cerebrospinal levels of melatonin derive primarily from the
      pineal gland, and that performs many biological functions. Our previous study
      demonstrated that melatonin promotes the proliferation of progenitor cells
      originating from the hippocampus. In this study, hippocampal progenitor cells
      from adult Wistar rats were used to determine the effects of METH on cell
      proliferation and the mechanisms underlying these effects. We investigated the
      effects of melatonin on the METH-induced alteration in cell proliferation. The
      results demonstrated that 500 MUm METH induced a decrease (63.0%) in neurosphere
      cell proliferation and altered the expression of neuronal phenotype markers in
      the neurosphere cell population. Moreover, METH induced an increase in the
      protein expression of the tumor suppressor p53 (124.4%) and the cell cycle
      inhibitor p21(CIP) (1) (p21) (128.1%), resulting in the accumulation of p21 in
      the nucleus. We also found that METH altered the expression of the N-methyl-d
      aspartate (NMDA) receptor subunits NR2A (79.6%) and NR2B (126.7%) and Ca(2+)
      /calmodulin-dependent protein kinase II (CAMKII) (74.0%). In addition,
      pretreatment with 1 MUm melatonin attenuated the effects induced by METH
      treatment. According to these results, we concluded that METH induces a reduction
      in cell proliferation by upregulating the cell cycle regulators p53/p21 and
      promoting the accumulation of p21 in the nucleus and that melatonin ameliorates
      these negative effects of METH.

PMID- 25752338
TI  - Glia: guardians, gluttons, or guides for the maintenance of neuronal
      connectivity?
AB  - An emerging aspect of neuronal-glial interactions is the connection glial cells
      have to synapses. Mounting research now suggests a far more intimate relationship
      than previously recognized. Moreover, the current evidence implicating synapse
      loss in neurodegenerative disease etiology is overwhelming, but the role of glia
      in the process of synaptic degeneration has only recently been considered in
      earnest. Each main class of glial cell, including astrocytes, oligodendrocytes,
      and microglia, performs crucial and multifaceted roles in the maintenance of
      synaptic function and excitability. As such, aging and/or neuronal stress from
      disease-related misfolded proteins may involve disruption of multiple non-cell
      autonomous synaptic support systems that are mediated by neighboring glia. In
      addition, glial cell activation induced by injury, ischemia, or neurodegeneration
      is thought to greatly alter the behavior of glial cells toward neuronal synapses,
      suggesting that neuroinflammation potentially contributes to synapse loss
      primarily mediated by altered glial functions. This review discusses recent
      evidence highlighting novel roles for glial cells at neuronal synapses and in the
      maintenance of neuronal connectivity, focusing primarily on their implications
      for neurodegenerative disease research. 

PMID- 25752341
TI  - Give 'em health, Harry.

PMID- 25752340
TI  - Traumatic Intracerebral Hemorrhage: Risk Factors Associated with Progression.
AB  - The increase in the volume of a traumatic intracerebral hemorrhage (TICH) is a
      widely studied phenomenon that has a direct impact on the prognosis of patients.
      The objective of this study was to identify the risk factors associated with the
      progression of TICH. We retrospectively analyzed the records of 1970 adult
      patients >15 years of age who were consecutively admitted after sustaining a
      closed severe traumatic brain injury (TBI) between January 1987 and November 2013
      at a single center. Beginning in 2007, patients with moderate TBIs were also
      included. A total of 782 patients exhibited one or more TICH on the initial CT
      scan, and met the selection criteria. The main outcome variable was the presence
      or absence of progression of the TICH. Univariate and multivariate statistical
      analyses were performed. Factors independently associated with the growth of TICH
      obtained through logistic regression included the following: an initial volume <5
      cc (odds ratio [OR] 2.42, p<0.001), cisternal compression (OR 1.95, p<0.001),
      decompressive craniectomy (OR 2.18, p<0.001), age (mean 37.67 vs. 42.95 years; OR
      1.01, p<0.001), falls as mechanism of trauma (OR 1.72, p=0.001), multiple TICHs
      (OR 1.56, p=0.007), and hypoxia (OR 1.56, p=0.02). TICH progression occurred with
      a frequency of 63% in our study. We showed that there was a correlation between
      TICH growth and some variables, such as multiple TICHs, a lower initial volume,
      acute subdural hematoma, cisternal compression, older patient age, hypoxia,
      falls, and decompressive craniectomy. 

PMID- 25752342
TI  - Swimming upstream: probing the problem of pollution.

PMID- 25752343
TI  - Hidden cross subsidies, planned obfuscation, and purposeful "overselling":
      business as usual or issues worthy of debate?

PMID- 25752344
TI  - Dear health care lobbyists . . .

PMID- 25752346
TI  - Can there be political common ground for improving population health?

PMID- 25752345
TI  - Good science + good ethics = good law: five rules for epidemic preparedness.

PMID- 25752347
TI  - Women's contribution to the health of the American population.

PMID- 25752348
TI  - Will health centers go over the "funding cliff "?

PMID- 25752349
TI  - A picture of progress on hospital errors.

PMID- 25752350
TI  - Benefits gained, benefits lost: comparing baby boomers to other generations in a
      longitudinal cohort study of self-rated health.
AB  - POLICY POINTS: Despite beliefs that baby boomers are healthier than previous
      generations, we found no evidence that the health of baby boomers is
      substantially different from that of the previous or succeeding cohorts. The
      effects of increased education, higher income, and lower smoking rates on
      improving self-rated health were nearly counterbalanced by the adverse effect of
      increasing body mass index (BMI). Assumptions that baby boomers will require less
      health care as they age because of better education, more prosperity, and less
      propensity to smoke may not be realized because of increases in obesity. CONTEXT:
      Baby boomers are commonly believed to be healthier than the previous generation.
      Using self-rated health (SRH) as an indicator of health status, this study
      examines the effects of age, period, and birth cohort on the trajectory of health
      across 4 generations: World War II (born between 1935 and 1944), older baby
      boomers (born between 1945 and 1954), younger baby boomers (born between 1955 and
      1964), and Generation X (born between 1965 and 1974). METHODS: We analyzed
      Canada's longitudinal National Population Health Survey 1994-2010 (n = 8,570 at
      baseline), using multilevel growth models to estimate the age trajectory of SRH
      by cohort, accounting for period and incorporating the influence of changes in
      education, household income, smoking status, and body mass index (BMI) on SRH
      over time. FINDINGS: SRH worsened with increasing age in all cohorts. Cohort
      differences in SRH were modest (p = 0.034), but there was a significant period
      effect (p = 0.002). We found marked cohort effects for increasing education,
      income, and BMI, and decreasing smoking from the youngest to the oldest cohorts,
      which were much reduced (education and smoking) or removed (income and BMI) once
      period was taken into account. At the population level, multivariable analysis
      showed the benefits of increasing education and income and declines in smoking on
      the trajectory of improving SRH were almost counterbalanced by the effects of
      increasing BMI (obesity). CONCLUSIONS: We found no evidence to support the
      expectation that baby boomers will age more or less healthily than previous
      cohorts did. We also found that increasing BMI has likely undermined improvements
      in health that might have otherwise occurred, with possible implications for the
      need for health care. Period effects had a more profound effect than birth cohort
      effects. This suggests that interventions to improve health, such as reducing
      obesity, can be targeted to the entire, or a major portion of the, population and
      need not single out particular birth cohorts.

PMID- 25752351
TI  - The role of parents in public views of strategies to address childhood obesity in
      the United States.
AB  - POLICY POINTS: The American public--both men and women and those with and without
      children in the household--holds parents highly responsible and largely to blame
      for childhood obesity. High attributions of responsibility to parents for
      reducing childhood obesity did not universally undermine support for broader
      policy action. School-based obesity prevention policies were strongly supported,
      even among those viewing parents as mostly to blame for childhood obesity.
      Americans who viewed sectors outside the family (such as the food and beverage
      industry, schools, and the government) as helping address childhood obesity were
      more willing to support a wider range of population-based obesity prevention
      policies. CONTEXT: The public's views of parents' behaviors and choices--and the
      attitudes held by parents themselves--are likely to influence the success of
      efforts to reverse obesity rates. METHODS: We analyzed data from 2 US national
      public opinion surveys fielded in 2011 and 2012 to examine attributions of blame
      and responsibility to parents for obesity, both among the general public and
      parents themselves, and we also explored the relationship between views of
      parents and support for obesity prevention policies. FINDINGS: We found that
      attribution of blame and responsibility to parents was consistently high,
      regardless of parental status or gender. Support for policies to curb childhood
      obesity also did not differ notably by parental status or gender. Multivariable
      analyses revealed consistent patterns in the association between public attitudes
      toward parents' responsibility and support for policies to curb childhood
      obesity. High parental responsibility was linked to higher support for school
      targeted policies but generally was not associated with policies outside the
      school setting. Attribution of greater responsibility to entities external to
      children and their parents (schools, the food and beverage industry, and the
      government) was associated with greater support for both school-targeted and
      population-based obesity prevention policies. CONCLUSIONS: Our findings suggest
      that the high attribution of responsibility to parents for reducing childhood
      obesity does not universally undermine support for broader policy action. But
      appealing to parents to rally support for preventing obesity in the same way as
      for other parent-initiated social movements (eg, drunk driving) may be
      challenging outside the school setting.

PMID- 25752353
TI  - Creating a science of homelessness during the Reagan era.
AB  - POLICY POINTS: A retrospective analysis of federally funded homeless research in
      the 1980s serves as a case study of how politics can influence social and
      behavioral science research agendas today in the United States. These studies of
      homeless populations, the first funded by the National Institute of Mental
      Health, demonstrated that only about a third of the homeless population was
      mentally ill and that a diverse group of people experienced homelessness. This
      groundbreaking research program set the mold for a generation of research and
      policy characterizing homelessness as primarily an individual-level problem
      rather than a problem with the social safety net. CONTEXT: A decade after the
      nation's Skid Rows were razed, homelessness reemerged in the early 1980s as a
      health policy issue in the United States. While activists advocated for
      government-funded programs to address homelessness, officials of the Reagan
      administration questioned the need for a federal response to the problem. In this
      climate, the National Institute of Mental Health (NIMH) launched a seminal
      program to investigate mental illness and substance abuse among homeless
      individuals. This program serves as a key case study of the social and behavioral
      sciences' role in the policy response to homelessness and how politics has shaped
      the federal research agenda. METHODS: Drawing on interviews with former
      government officials, researchers, social activists, and others, along with
      archival material, news reports, scientific literature, and government
      publications, this article examines the emergence and impact of social and
      behavioral science research on homelessness. FINDINGS: Research sponsored by the
      NIMH and other federal research bodies during the 1980s produced a rough picture
      of mental illness and substance abuse prevalence among the US homeless
      population, and private foundations supported projects that looked at this
      group's health care needs. The Reagan administration's opposition to funding
      "social research," together with the lack of private-sector support for such
      research, meant that few studies examined the relationship between homelessness
      and structural factors such as housing, employment, and social services.
      CONCLUSIONS: The NIMH's homelessness research program led to improved
      understanding of substance abuse and mental illness in homeless populations. Its
      primary research focus on behavioral disorders nevertheless unwittingly
      reinforced the erroneous notion that homelessness was rooted solely in individual
      pathology. These distortions, shaped by the Reagan administration's policies and
      reflecting social and behavioral scientists' long-standing tendencies to
      emphasize individual and cultural rather than structural aspects of poverty,
      fragmented homelessness research and policy in enduring ways.

PMID- 25752352
TI  - Race/Ethnicity and overuse of care: a systematic review.
AB  - POLICY POINTS: Racial/ethnic differences in the overuse of care (specifically,
      unneeded care that does not improve patients' outcomes) have received little
      scholarly attention. Our systematic review of the literature (59 studies) found
      that the overuse of care is not invariably associated with race/ethnicity, but
      when it was, a substantial proportion of studies found greater overuse of care
      among white patients. The absence of established subject terms in PubMed for the
      overuse of care or inappropriate care impedes the ability of researchers or
      policymakers to synthesize prior scientific or policy efforts. CONTEXT: The
      literature on disparities in health care has examined the contrast between white
      patients receiving needed care, compared with racial/ethnic minority patients not
      receiving needed care. Racial/ethnic differences in the overuse of care, that is,
      unneeded care that does not improve patients' outcomes, have received less
      attention. We systematically reviewed the literature regarding race/ethnicity and
      the overuse of care. METHODS: We searched the Medline database for US studies
      that included at least 2 racial/ethnic groups and that examined the association
      between race/ethnicity and the overuse of procedures, diagnostic (care) or
      therapeutic care. In a recent review, we identified studies of overuse by
      race/ethnicity, and we also examined reference lists of retrieved articles. We
      then abstracted and evaluated this information, including the population studied,
      data source, sample size and assembly, type of care, guideline or appropriateness
      standard, controls for clinical confounding and financing of care, and findings.
      FINDINGS: We identified 59 unique studies, of which 11 had a low risk of
      methodological bias. Studies with multiple outcomes were counted more than once;
      collectively they assessed 74 different outcomes. Thirty-two studies, 6 with low
      risks of bias (LRoB), provided evidence that whites received more inappropriate
      or nonrecommended care than racial/ethnic minorities did. Nine studies (2 LRoB)
      found evidence of more overuse of care by minorities than by whites. Thirty-three
      studies (6 LRoB) found no relationship between race/ethnicity and overuse.
      CONCLUSIONS: Although the overuse of care is not invariably associated with
      race/ethnicity, when it was, a substantial proportion of studies found greater
      overuse of care among white patients. Clinicians and researchers should try to
      understand how and why race/ethnicity might be associated with overuse and to
      intervene to reduce it.

PMID- 25752354
TI  - Policy commercializing nonprofits in health: the history of a paradox from the
      19th century to the ACA.
AB  - POLICY POINTS: Health policy in the United States has, for more than a century,
      simultaneously and paradoxically incentivized the growth as well as the
      commercialization of nonprofit organizations in the health sector. This policy
      paradox persists during the implementation of the Affordable Care Act of 2010.
      CONTEXT: For more than a century, policy in the United States has incentivized
      both expansion in the number and size of tax-exempt nonprofit organizations in
      the health sector and their commercialization. The implementation of the
      Affordable Care Act of 2010 (ACA) began yet another chapter in the history of
      this policy paradox. METHODS: This article explores the origin and persistence of
      the paradox using what many scholars call "interpretive social science." This
      methodology prioritizes history and contingency over formal theory and methods in
      order to present coherent and plausible narratives of events and explanations for
      them. These narratives are grounded in documents generated by participants in
      particular events, as well as conversations with them, observing them in action,
      and analysis of pertinent secondary sources. The methodology achieves validity
      and reliability by gathering information from multiple sources and making
      disciplined judgments about its coherence and correspondence with reality.
      FINDINGS: A paradox with deep historical roots persists as a result of consensus
      about its value for both population health and the revenue of individuals and
      organizations in the health sector. Participants in this consensus include
      leaders of governance who have disagreed about many other issues. The paradox
      persists because of assumptions about the burden of disease and how to address
      it, as well as about the effects of biomedical science that is translated into
      professional education, practice, and the organization of services for the
      prevention, diagnosis, treatment, and management of illness. CONCLUSIONS: The
      policy paradox that has incentivized the growth and commercialization of
      nonprofits in the health sector since the late 19th century remains influential
      in health policy, especially for the allocation of resources. However, aspects of
      the implementation of the ACA may constrain some of the effects of the paradox.

PMID- 25752356
TI  - Exercise-induced vasodilation in healthy males: A marker of reduced endothelial
      function.
AB  - OBJECTIVES: Reduced arterial vasodilatatory capacity is a marker of coronary
      heart disease. The aim was to investigate if the difference between the
      vasodilatory response before and after exercise, as assessed by non-invasive
      methodology, is related to endothelial and inflammatory biomarkers. DESIGN: Post
      ischemic hyperemia after 5 min of arterial occlusion was examined before and
      after a bicycle test with strain-gauge plethysmography (measuring peak reactive
      hyperemia in the forearm) and peripheral arterial tonometry (PAT hyperemia ratio:
      measuring pulse waves in the index finger relative to the contra-lateral index
      finger) in 30 healthy males. A low PAT hyperemia ratio or a low peak reactive
      hyperemia reflects endothelial dysfunction. Inflammatory and endothelial
      biomarkers were assessed. RESULTS: A low peak reactive hyperemia and a low PAT
      hyperemia ratio before the bicycle test was associated with a high percentage
      increase in peak reactive hyperemia after exercise (r = - 0.68, p < 0.001; r = -
      0.35, p = 0.06, respectively). Asymmetric dimethylarginine and interleukin-10
      were associated with the percentage increase in peak reactive hyperemia in
      multiple linear regression analyses (beta: 165 (confidence interval [CI], 34
      296), p = 0.02; beta: 19 (CI, - 0.5-39), p = 0.06, respectively). CONCLUSIONS:
      The difference in the vasodilatory response before and after exercise, as
      assessed by non-invasive methodology, is related to endothelial and inflammatory
      biomarkers in healthy males.

PMID- 25752357
TI  - Comparison Between 10- and 14-Day Hybrid Regimens for Helicobacter pylori
      Eradication: A Randomized Clinical Trial.
AB  - BACKGROUND: Helicobacter pylori (H. pylori) eradication has always been a
      concern. In our previous study, 14-day hybrid regimen showed ideal results. Based
      on these findings, we decided to compare the efficacy of 10- and 14-day hybrid
      regimens for H. pylori eradication. METHODS: Two hundred and seventy patients
      with peptic ulcer disease and H. pylori infection were enrolled in the study. One
      hundred and thirty-four patients received 10-day hybrid regimen (PACT-10):
      pantoprazole, 40 mg, and amoxicillin, 1 g, both twice daily for 10 days; plus
      clarithromycin, 500 mg, and tinidazole, 500 mg, both twice daily just during the
      last 5 days. One hundred and thirty-six patients received 14-day hybrid regimen
      (PACT-14): pantoprazole, 40 mg, and amoxicillin, 1 g, both twice a day for 14
      days; plus clarithromycin, 500 mg, and tinidazole, 500 mg, both twice daily just
      for the last 7 days. Eight weeks after treatment, (14) C-urea breath test was
      performed to evaluate H. pylori eradication. RESULTS: Two hundred and fifty
      patients (124 patients in PACT-10 and 126 patients in PACT-14 regimens) completed
      the study. The intention-to-treat eradication rates were 77.6% (95% confidence
      interval (CI): 70.6-84.6%) and 86% (95% CI: 80-92%) for the two regimens,
      respectively (p = .17). Per-protocol eradication rates were 83.8% (95% CI: 80
      86%) and 92.8% (95% CI: 88-96%), respectively (p < .01). There were no
      significant intergroup differences in compliance to treatment or discontinuation
      of therapy due to severe side effects. CONCLUSION: Ten-day hybrid regimen could
      not achieve acceptable eradication rate. However, 14-day hybrid regimen seems to
      be an acceptable option for H. pylori eradication in Iran.

PMID- 25752358
TI  - Sarcoidosis: "thinking out of the box is often a matter of perspective".

PMID- 25752360
TI  - How do community-based HIV prevention programmes for men who have sex with men
      'travel'? Lessons from the Ukwazana/Zwakalani journey in South Africa.
AB  - Research reveals how homophobia and stigma link closely to HIV among men who have
      sex with men in sub-Saharan Africa. This paper considers the varying impact of
      homophobic stigma on HIV prevention programmes among men who have sex with men in
      South Africa. It explores how a community-based HIV prevention programme based in
      the peri-urban townships of Cape Town was 'translated' to peri-urban
      Johannesburg. Drawing on interviews with volunteers and programme facilitators in
      Johannesburg, it argues that an altered homophobic environment to that found in
      Cape Town gave different opportunities to engage both with other men who have sex
      with men and the broader community. It also argues that programme facilitators
      should be mindful of how varying degrees of homophobic stigma may relate to
      broader theoretical debates about sexual binary relationships, which can help us
      understand why particular programmes choose to focus on certain activities rather
      than others. 

PMID- 25752361
TI  - Proceedings of the 116th Meeting of the British Neuropathological Society,
      Institute of Child Health, 4-6 March, 2015, London, UK.

PMID- 25752359
TI  - Spatial and temporal dynamics of the cardiac mitochondrial proteome.
AB  - Mitochondrial proteins alter in their composition and quantity drastically
      through time and space in correspondence to changing energy demands and cellular
      signaling events. The integrity and permutations of this dynamism are
      increasingly recognized to impact the functions of the cardiac proteome in health
      and disease. This article provides an overview on recent advances in defining the
      spatial and temporal dynamics of mitochondrial proteins in the heart. Proteomics
      techniques to characterize dynamics on a proteome scale are reviewed and the
      physiological consequences of altered mitochondrial protein dynamics are
      discussed. Lastly, we offer our perspectives on the unmet challenges in
      translating mitochondrial dynamics markers into the clinic.

PMID- 25752362
TI  - Manual small incision extracapsular cataract surgery in Australia: comment.

PMID- 25752364
TI  - High-Mobility Group Box 1 Protein in Myocardial Infarction: Should it be
      Stimulated or Inhibited?

PMID- 25752365
TI  - Decompressive craniectomy in the treatment of post-traumatic intracranial
      hypertension in children: our philosophy and indications.
AB  - Decompressive craniotomy (DC) in children is a life-saving procedure for the
      treatment of refractory intracranial hypertension related to traumatic, ischemic
      and infectious lesions. Different surgical procedures have been proposed
      including uni or bilateral hemicraniectomy, bi-frontal, bi-temporal, or bi
      parietal craniotomies. DC can avoid the cascade of events related to tissue
      hypoxia, brain perfusion reduction, hypotension and the evolution of brain edema
      that can be responsible for brain herniation. The monitoring of intracranial
      pressure (ICP) is very important to take a decision as well as the value of Trans
      cranial Doppler (TCD). Repeated TCD in the intensive care unit give important
      information about the decrease of the cerebral perfusion pressure (CPP) and
      facilitates the decision making. The important question is about how long time we
      have to wait before to perform the DC. Three conditions can be distinguished: 1)
      ICP stable and TCD with good parameters: the decision can be postponed; 2) ICP>20
      mmHg with good TCD and without clinical signs of deterioration: the decision can
      be postponed; 3) ICP>20 mmHg with altered CPP and degraded TCD value and clinical
      signs of brain herniation: the surgical procedure is indicated. The decision of a
      ventricular drainage can also be discussed but in cases of slit ventricles it is
      preferable to realize a DC to avoid the problems of multiple taps without finding
      the ventricular system. In some very specific situations, DC has to be
      contraindicated. The first one is a prolonged cardiopulmonary arrest with a no
      flow longer than 15 minutes and irreversible lesions on the TCD or on the CT
      scan. The second most common situation is a patient with GCS of 3 on admission
      associated with bilaterally fixed dilated pupils. In this case TCD is very useful
      to document the decrease or the absence of diastolic flux that indicates a very
      poor cerebral perfusion. In case of severe polytraumatism with multiorgan
      failure, especially in very severe hemorrhagic shock with incontrollable
      coagulopathy, the realization of DC is definitely hazardous with y a high risk of
      cardiac arrest during the surgical procedure. The decision to realize a
      hemicraniectomy or a bi-frontal craniotomy is related to the presence or not of
      associated traumatic lesions as hemorrhagic contusions or a sub-dural or
      extradural hematoma. In cases of diffuse cerebral edema the bi-frontal bone flap
      is indicated. In all cases a closure of the dura mater with a large dural patch
      has to be performed avoiding compression of the nervous system. Our results
      showed a mortality rate of 18%. Eighty percent of the survivors have a good
      quality of life but only 43% in a scholar age could attend a normal program.
      Patients treated with DC need a long follow-up and an important rehabilitation
      program to improve their quality of life. Our report shows that DC in children is
      effective to control the post-traumatic intracranial hypertension but a long
      follow-up is recommended to access the sequels and quality of life of these
      patients. 

PMID- 25752363
TI  - Angiotensin II Activates MCP-1 and Induces Cardiac Hypertrophy and Dysfunction
      via Toll-like Receptor 4.
AB  - AIM: Angiotensin II(Ang II) produces reactive oxygen species (ROS), thus
      contributing to the development of cardiac hypertrophy and subsequent heart
      failure, and stimulates the expression of monocyte chemoattractant protein-1 (MCP
      1). In addition, Toll-like receptor 4 (TLR4) is involved in the upregulation of
      MCP-1. In order to clarify whether TLR4 is involved in the onset of cardiac
      dysfunction caused by Ang II stimulation, we investigated the effects of TLR4 on
      oxidative stress, the MCP-1 expression and cardiac dysfunction in mice with Ang
      II-induced hypertension. METHODS: TLR4-deficient (Tlr4(lps-d)) and wild-type (WT)
      mice were randomized into groups treated with Ang II, norepinephrine (NE) or a
      subdepressor dose of the Ang IIreceptor blocker irbesartan (IRB) and Ang II for
      two weeks. RESULTS: Ang II and NE similarly increased systolic blood pressure in
      all drug-treated groups compared to that observed in the control group among both
      WT and Tlr4(lps-d) mice (p<0.05). In the WT mice, Ang II induced cardiac
      hypertrophy as well as vascular remodeling and perivascular fibrosis of the
      intramyocardial arteries and monocyte/macrophage infiltration in the heart
      (p<0.05). Furthermore, Ang II treatment decreased the left ventricular diastolic
      function and resulted in a greater left ventricular end-systolic dimension
      (p<0.05) in addition to producing a five-fold increase in the NADPH oxidase
      activity, ROS content and MCP-1 expression (p<0.05). In contrast, the Tlr4(lps-d)
      mice showed little effects of Ang II on these indices. In the WT mice, IRB
      treatment reversed these changes compared to that seen in the mice treated with
      Ang II alone. NE produced little effect on any of the indices in either the WT or
      Tlr4(lps-d) mice. CONCLUSIONS: TLR4 may be involved in the processes underlying
      the increased oxidative stress, selectively activated MCP-1 expression and
      cardiac hypertrophy and dysfunction seen in cases of Ang II- induced
      hypertension.

PMID- 25752366
TI  - Following the canyon to reach and remove olfactory groove meningiomas.
AB  - BACKGROUND: Olfactory groove meningiomas (OGMs) represent approximately 10% of
      all intracranial meningiomas. They arise in the olfactory fossa, a variable
      depression delimited by the lateral lamella and perpendicular plate. The
      cribriform plate with the lateral lamella and ethmoidal and orbital roof could be
      viewed as a 'canyon' with the frontal sinus as the main entrance. METHODS:
      Between January 2000 and December 2013, 32 consecutive patients underwent removal
      of OGMs through this 'canyon' at the Department of Neurosurgery of Brescia and
      Turin. Complete removal was achieved in all patients with this trans-frontal
      sinus subcranial approach (Simpson grade I; mean lesion volume, 46.6 cm3).
      RESULTS: Five patients (15.6%) experienced nasal CSF leakage, treated with
      external lumbar drain positioning for 4 days and resolved in all cases but one,
      which was re-operated. Two patients (6.2%) during the CSF leakage experienced
      meningitis at day 7 after surgery, both successfully treated by intravenous
      antibiotic therapy. After one month, one patient developed hydrocephalus, treated
      with a ventricular peritoneal shunt. In one patient, traction on the OGM caused
      bleeding of the callosomarginal artery, which was coagulated with superior
      frontal gyrus ischemia without neurological consequences. Glasgow Outcome Scale
      Score at 6 months was V in 29 patients, IV in one patient, and I in two patients.
      CONCLUSIONS: Advantages with this approach may include easy and early control of
      blood supply from its insertion in the skull base, minimal frontal lobe
      retraction, preservation of the frontal veins draining to the sagittal sinus, and
      a satisfactory aesthetic outcome.

PMID- 25752367
TI  - Evidence of the synergistic interaction of honey bee pathogens Nosema ceranae and
      Deformed wing virus.
AB  - Nosema ceranae and Deformed wing virus (DWV) are two of the most prevalent
      pathogens currently attacking Western honey bees, Apis mellifera, and often
      simultaneously infect the same hosts. Here we investigated the effect of N.
      ceranae and Deformed wing virus (DWV) interactions on infected honey bees under
      lab conditions and at different nutrition statuses. Our results showed that
      Nosema could accelerate DWV replication in infected bees in a dose-dependent
      manner at the early stages of DWV infection. When bees were restricted from
      pollen nutrition, inoculation with 1*10(4) and 1*10(5) spores/bee could cause a
      significant increase in DWV titer, while inoculation with 1*10(3) spores/bee did
      not show any significant effect on the DWV titer. When bees were provided with
      pollen, only inoculation with 1*10(5) spores/bee showed significant effect on DWV
      titer. However, our results also showed that the two pathogens did not act
      synergistically when the titer of DWV reached a plateau. This study suggests that
      the synergistic effect of N. ceranae and DWV is dosage- and nutrition-dependent
      and that the synergistic interactions between the two pathogens could have
      implications on honey bee colony losses.

PMID- 25752368
TI  - Erythema nodosum-like lesions during BRAF inhibitor therapy: Report on 16 new
      cases and review of the literature.
AB  - IMPORTANCE: BRAF inhibitors have been licensed for the therapy of BRAF-mutated
      melanoma. Recently, inflammatory skin lesions clinically resembling erythema
      nodosum have been reported as therapy side-effects that may lead to treatment
      discontinuation. OBJECTIVE: To identify and characterize cases with BRAF
      inhibitor-associated erythema nodosum-like inflammatory skin lesions and
      development of an algorithm for their management. DESIGN AND SETTING:
      Retrospective chart review of melanoma patients treated with BRAF inhibitors in
      14 departments of Dermatology in Germany and Austria and PubMed search for cases
      in the literature. RESULTS: Sixteen patients were identified who developed
      erythema nodosum-like lesions under BRAF inhibitor therapy; 14 had received
      vemurafenib and two dabrafenib plus trametinib. The most frequently involved body
      sites were the legs. Histopathology was performed in five cases and revealed
      panniculitis in three and vasculitis in two patients respectively. Arthralgia and
      fever were associated symptoms in 44% and 31% of patients respectively.
      Inflammatory symptoms led to discontinuation of treatment in three patients,
      while in the majority of cases symptomatic management was sufficient. Skin
      lesions finally resolved despite continued BRAF inhibitor therapy in seven
      patients. In the literature, 19 additional patients with similar cutaneous
      appearance under BRAF inhibitors could be identified. An algorithm for the
      management of such lesions is proposed. CONCLUSION: Erythema nodosum-like skin
      lesions histologically correspond to panniculitis and/or vasculitis. Symptomatic
      treatment may be sufficient. However, additional work-up and interruption of BRAF
      inhibitor therapy may be necessary in severe cases which are commonly associated
      with systemic symptoms.

PMID- 25752369
TI  - Discussion.

PMID- 25752370
TI  - Survival into adulthood of patients with atrial isomerism undergoing cardiac
      surgery.
AB  - OBJECTIVES: To identify determinants of adverse outcomes in patients with atrial
      isomerism. METHODS: Determinants of survival were analyzed for the group as a
      whole as well as separately for left and right atrial isomerism. RESULTS: There
      were 78 cases with right and 104 with left atrial isomerism. Nineteen patients
      were not offered surgery; 49 (47%) of those with left atrial isomerism and 60
      (77%) with right atrial isomerism were directed to single ventricle palliation. A
      total of 67 patients died. Survival to 25 years was 62% (95% confidence interval
      [CI], 53%-69%). Independent predictors of mortality were obstructed total
      anomalous pulmonary venous drainage (P < .001; hazard ratio [HR], 5.2; 95% CI,
      2.7-9.7) and asplenia (P = .008; HR, 2; 95% CI, 1.2-3.3). There was no evidence
      that patients born in the recent era had improved survival (P = .47; HR, 1.1; 95%
      CI, 0.8-1.5). Survival was better for patients with left than right atrial
      isomerism: 18 years survival 74% (95% CI, 63%-82%) versus 50% (95% CI, 38%-60%).
      Independent predictors of mortality for patients with left atrial isomerism were
      dextrocardia (P = .009; HR, 3.0; 95% CI, 1.3-6.7) and pulmonary stenosis (P =
      .042; HR, 0.3; 95% CI, 0.1-0.9) and patients with right atrial isomerism,
      biventricular repair (P < .001; HR, 6.0; 95% CI, 2.8-13), and obstructed total
      anomalous pulmonary venous drainage (P < .001; HR, 4.2; 95% CI, 2.0-8.6).
      CONCLUSIONS: A significant proportion of patients with isomerism still die before
      reaching adulthood. Only a fraction of those with obstructed pulmonary veins
      survive. Having biventricular repair does not confer a survival advantage to
      those born with right atrial isomerism.

PMID- 25752371
TI  - Aortic valve repair: Intraoperative evaluation of valve geometry by angioscopy.

PMID- 25752373
TI  - Requiem for a good mechanical heart valve: Farewell to the Medtronic Hall valve.

PMID- 25752374
TI  - Outcomes, quality of life, and survival after esophagectomy for squamous cell
      carcinoma: A propensity score-matched comparison of operative approaches.
AB  - BACKGROUND: Minimally invasive esophagectomy (MIE) theoretically offers
      advantages compared with open esophagectomy (OE). However, the long-term outcomes
      have not been well studied, especially for esophageal squamous cell carcinoma. We
      retrospectively compared postoperative outcomes, quality of life (QOL), and
      survival in a matched population of patients undergoing MIE, with a control (OE)
      group. METHODS: From May 2004 to August 2013, MIE was performed for a group of
      735 patients, which was compared with a group of 652 cases of OE. Eventually, 444
      paired cases, matched using propensity-score matching, were selected for further
      statistical analysis. RESULTS: Compared with the OE group, the MIE group had
      shorter operation duration (191 +/- 47 minutes vs 211 +/- 44 minutes, P < .001);
      less blood loss (135 +/- 74 ml vs 163 +/- 84 ml, P < .001); similar lymph node
      harvest (24.1 +/- 6.2 vs 24.3 +/- 6.0, P = .607); shorter postoperative hospital
      stay (11 days [range: 7-90 days] vs 12 days [range: 8-112 days], P < .001); fewer
      major complications (30.4% vs 36.9%, P = .039); a lower readmission rate to the
      intensive-care unit (5.6% vs 9.7%, P = .023); and similar perioperative mortality
      (1.1% vs 2.0%, P = .281). At a median follow-up of 27 months, the 2-year overall
      survival rates in the MIE and OE group were: (1) stage 0 and I: 92% versus 90% (P
      = .864); (2) stage II: 83% versus 82% (P = .725); (3) stage III: 59% versus 55%
      (P = .592); (4) stage IV: 43% versus 43% (P = .802). The generalized estimating
      equation analysis showed that MIE had an independently positive impact on
      patients' postoperative QOL. CONCLUSIONS: In our experience, MIE is a safe and
      effective procedure for the treatment of esophageal squamous cell carcinoma. It
      may offer better perioperative outcomes, better postoperative QOL, and equal
      oncologic survival, compared with OE.

PMID- 25752375
TI  - "Glow in the dark" intraoperative imaging: Expanding the capabilities of robotic
      technology.

PMID- 25752377
TI  - The challenge of global radiation therapy: an IAEA perspective.

PMID- 25752378
TI  - Clinical target volume delineation for rectal cancer radiation therapy: time for
      updated guidelines?

PMID- 25752379
TI  - Radiation oncology in Italy: the past, the present, the future.

PMID- 25752380
TI  - The far-reaching subject matter of medical physics in radiation oncology.

PMID- 25752381
TI  - Image guided radiation therapy: really?

PMID- 25752382
TI  - Phase 3 trials of stereotactic radiosurgery with or without whole-brain radiation
      therapy for 1 to 4 brain metastases: individual patient data meta-analysis.
AB  - PURPOSE: To perform an individual patient data (IPD) meta-analysis of randomized
      controlled trials evaluating stereotactic radiosurgery (SRS) with or without
      whole-brain radiation therapy (WBRT) for patients presenting with 1 to 4 brain
      metastases. METHOD AND MATERIALS: Three trials were identified through a
      literature search, and IPD were obtained. Outcomes of interest were survival,
      local failure, and distant brain failure. The treatment effect was estimated
      after adjustments for age, recursive partitioning analysis (RPA) score, number of
      brain metastases, and treatment arm. RESULTS: A total of 364 of the pooled 389
      patients met eligibility criteria, of whom 51% were treated with SRS alone and
      49% were treated with SRS plus WBRT. For survival, age was a significant effect
      modifier (P=.04) favoring SRS alone in patients <=50 years of age, and no
      significant differences were observed in older patients. Hazard ratios (HRs) for
      patients 35, 40, 45, and 50 years of age were 0.46 (95% confidence interval [CI]
      = 0.24-0.90), 0.52 (95% CI = 0.29-0.92), 0.58 (95% CI = 0.35-0.95), and 0.64 (95%
      CI = 0.42-0.99), respectively. Patients with a single metastasis had
      significantly better survival than those who had 2 to 4 metastases. For distant
      brain failure, age was a significant effect modifier (P=.043), with similar rates
      in the 2 arms for patients <=50 of age; otherwise, the risk was reduced with WBRT
      for patients >50 years of age. Patients with a single metastasis also had a
      significantly lower risk of distant brain failure than patients who had 2 to 4
      metastases. Local control significantly favored additional WBRT in all age
      groups. CONCLUSIONS: For patients <=50 years of age, SRS alone favored survival,
      in addition, the initial omission of WBRT did not impact distant brain relapse
      rates. SRS alone may be the preferred treatment for this age group.

PMID- 25752383
TI  - Local therapies for brain metastases, competing risks, and overall survival.

PMID- 25752385
TI  - Prostate hypofractionated radiation therapy with injection of hyaluronic acid:
      acute toxicities in a phase 2 study.
AB  - PURPOSE: Hypofractionated radiation therapy (RT) in prostate cancer can be
      developed only if the risk of rectal toxicity is controlled. In a multicenter
      phase 2 trial, hypofractionated irradiation was combined with an injection of
      hyaluronic acid (HA) to preserve the rectal wall. Tolerance of the injection and
      acute toxicity rates are reported. METHODS AND MATERIALS: The study was designed
      to assess late grade 2 toxicity rates. The results described here correspond to
      the secondary objectives. Acute toxicity was defined as occurring during RT or
      within 3 months after RT and graded according to the Common Terminology Criteria
      for Adverse Events version 4.0. HA tolerance was evaluated with a visual analog
      scale during the injection and 30 minutes after injection and then by use of the
      Common Terminology Criteria at each visit. RESULTS: From 2010 to 2012, 36
      patients with low-risk to intermediate-risk prostate cancer were included. The HA
      injection induced a mean pain score of 4.6/10 +/- 2.3. Thirty minutes after the
      injection, 2 patients still reported pain (2/10 and 3/10), which persisted after
      the intervention. Thirty-three patients experienced at least 1 acute
      genitourinary toxicity and 20 patients at least 1 acute gastrointestinal
      toxicity. Grade 2 toxicities were reported for 19 patients with urinary
      obstruction, frequency, or both and for 1 patient with proctitis. No grade 3 or 4
      toxicities were reported. At the 3-month visit, 4 patients described grade 2
      obstruction or frequency, and no patients had any grade 2 gastrointestinal
      toxicities. CONCLUSIONS: The injection of HA makes it possible to deliver
      hypofractionated irradiation over 4 weeks with a dose per fraction of > 3 Gy,
      with limited acute rectal toxicity.

PMID- 25752384
TI  - Metabolic tumor volume as a prognostic imaging-based biomarker for head-and-neck
      cancer: pilot results from Radiation Therapy Oncology Group protocol 0522.
AB  - PURPOSE: To evaluate candidate fluorodeoxyglucose positron emission
      tomography/computed tomography (FDG-PET/CT) imaging biomarkers for head-and-neck
      chemoradiotherapy outcomes in the cooperative group trial setting. METHODS AND
      MATERIALS: Radiation Therapy Oncology Group (RTOG) protocol 0522 patients
      consenting to a secondary FDG-PET/CT substudy were serially imaged at baseline
      and 8 weeks after radiation. Maximum standardized uptake value (SUVmax), SUV peak
      (mean SUV within a 1-cm sphere centered on SUVmax), and metabolic tumor volume
      (MTV) using 40% of SUVmax as threshold were obtained from primary tumor and
      involved nodes. RESULTS: Of 940 patients entered onto RTOG 0522, 74 were
      analyzable for this substudy. Neither high baseline SUVmax nor SUVpeak from
      primary or nodal disease were associated with poor treatment outcomes. However,
      primary tumor MTV above the cohort median was associated with worse local
      regional control (hazard ratio 4.01, 95% confidence interval 1.28-12.52, P=.02)
      and progression-free survival (hazard ratio 2.34, 95% confidence interval 1.02
      5.37, P=.05). Although MTV and T stage seemed to correlate (mean MTV 6.4, 13.2,
      and 26.8 for T2, T3, and T4 tumors, respectively), MTV remained a strong
      independent prognostic factor for progression-free survival in bivariate analysis
      that included T stage. Primary MTV remained prognostic in p16-associated
      oropharyngeal cancer cases, although sample size was limited. CONCLUSION: High
      baseline primary tumor MTV was associated with worse treatment outcomes in this
      limited patient subset of RTOG 0522. Additional confirmatory work will be
      required to validate primary tumor MTV as a prognostic imaging biomarker for
      patient stratification in future trials.

PMID- 25752386
TI  - Acute toxicity after image-guided intensity modulated radiation therapy compared
      to 3D conformal radiation therapy in prostate cancer patients.
AB  - PURPOSE: Image-guided intensity modulated radiation therapy (IG-IMRT) allows
      significant dose reductions to organs at risk in prostate cancer patients.
      However, clinical data identifying the benefits of IG-IMRT in daily practice are
      scarce. The purpose of this study was to compare dose distributions to organs at
      risk and acute gastrointestinal (GI) and genitourinary (GU) toxicity levels of
      patients treated to 78 Gy with either IG-IMRT or 3D-CRT. METHODS AND MATERIALS:
      Patients treated with 3D-CRT (n=215) and IG-IMRT (n=260) receiving 78 Gy in 39
      fractions within 2 randomized trials were selected. Dose surface histograms of
      anorectum, anal canal, and bladder were calculated. Identical toxicity
      questionnaires were distributed at baseline, prior to fraction 20 and 30 and at
      90 days after treatment. Radiation Therapy Oncology Group (RTOG) grade >=1, >=2,
      and >=3 endpoints were derived directly from questionnaires. Univariate and
      multivariate binary logistic regression analyses were applied. RESULTS: The
      median volumes receiving 5 to 75 Gy were significantly lower (all P<.001) with IG
      IMRT for anorectum, anal canal, and bladder. The mean dose to the anorectum was
      34.4 Gy versus 47.3 Gy (P<.001), 23.6 Gy versus 44.6 Gy for the anal canal
      (P<.001), and 33.1 Gy versus 43.2 Gy for the bladder (P<.001). Significantly
      lower grade >=2 toxicity was observed for proctitis, stool frequency >=6/day, and
      urinary frequency >=12/day. IG-IMRT resulted in significantly lower overall RTOG
      grade >=2 GI toxicity (29% vs 49%, respectively, P=.002) and overall GU grade >=2
      toxicity (38% vs 48%, respectively, P=.009). CONCLUSIONS: A clinically meaningful
      reduction in dose to organs at risk and acute toxicity levels was observed in IG
      IMRT patients, as a result of improved technique and tighter margins. Therefore
      reduced late toxicity levels can be expected as well; additional research is
      needed to quantify such reductions.

PMID- 25752387
TI  - Patterns of recurrence after low-dose-rate prostate brachytherapy: a population
      based study of 2223 consecutive low- and intermediate-risk patients.
AB  - OBJECTIVES: This study examined patterns of recurrence after low-dose-rate
      prostate brachytherapy (LDR-PB), estimated local recurrence rate and compared
      that rate to the estimated local recurrence rate after radical prostatectomy
      (RP). METHODS AND MATERIALS: A prospective database was maintained with clinical,
      dosimetric, and outcome data for all LDR-PB implantation procedures performed at
      our institution. From 1998 to 2008, 2223 patients with prostate cancer received
      LDR-PB without supplemental external beam radiation therapy. Patients who
      developed Phoenix-defined biochemical failure were reviewed for sites of relapse
      and investigations completed. RESULTS: At a median follow-up of 5 years, 108 of
      2223 patients (4.8%) developed biochemical relapse. In 1 additional patient,
      local relapse was found on transurethral prostate resection, but his prostate
      specific antigen concentration was well short of triggering Phoenix-defined
      failure. Of the 109 patients with disease relapse, 18 of 2223 (0.8%) had a proven
      local recurrence, and 30 of 2223 (1.3%) had a proven distant recurrence. The
      remaining 61 of 2223 patients (2.7%) had unidentified sites of recurrence; of
      these, 57 patients (93%) had digital rectal examinations (DREs), 18 (30%) had
      post-treatment biopsies, 45 (74%) had bone scans, and 34 (56%) had computed
      tomography imaging of the abdomen and pelvis. If every biochemical failure were
      local, the local recurrence rate would be as high as 4.9%; however, by excluding
      those with proven distant failure and those with both a negative DRE and biopsy,
      we estimate that the local recurrence rate is 2.7% or less. CONCLUSIONS: In the
      context of limitations of the study design, our population-based analysis
      indicates that the local recurrence rate after LDR-PB is as low or lower than
      that after RP in our jurisdiction.

PMID- 25752388
TI  - Assessing adverse events of postprostatectomy radiation therapy for prostate
      cancer: evaluation of outcomes in the Regione Emilia-Romagna, Italy.
AB  - PURPOSE: Although the likelihood of radiation-related adverse events influences
      treatment decisions regarding radiation therapy after prostatectomy for eligible
      patients, the data available to inform decisions are limited. This study was
      designed to evaluate the genitourinary, gastrointestinal, and sexual adverse
      events associated with postprostatectomy radiation therapy and to assess the
      influence of radiation timing on the risk of adverse events. METHODS: The Regione
      Emilia-Romagna Italian Longitudinal Health Care Utilization Database was queried
      to identify a cohort of men who received radical prostatectomy for prostate
      cancer during 2003 to 2009, including patients who received postprostatectomy
      radiation therapy. Patients with prior radiation therapy were excluded. Outcome
      measures were genitourinary, gastrointestinal, and sexual adverse events after
      prostatectomy. Rates of adverse events were compared between the cohorts who did
      and did not receive postoperative radiation therapy. Multivariable Cox
      proportional hazards models were developed for each class of adverse events,
      including models with radiation therapy as a time-varying covariate. RESULTS: A
      total of 9876 men were included in the analyses: 2176 (22%) who received
      radiation therapy and 7700 (78%) treated with prostatectomy alone. In
      multivariable Cox proportional hazards models, the additional exposure to
      radiation therapy after prostatectomy was associated with increased rates of
      gastrointestinal (rate ratio [RR] 1.81; 95% confidence interval [CI] 1.44-2.27;
      P<.001) and urinary nonincontinence events (RR 1.83; 95% CI 1.83-2.80; P<.001)
      but not urinary incontinence events or erectile dysfunction. The addition of the
      time from prostatectomy to radiation therapy interaction term was not significant
      for any of the adverse event outcomes (P>.1 for all outcomes). CONCLUSION:
      Radiation therapy after prostatectomy is associated with an increase in
      gastrointestinal and genitourinary adverse events. However, the timing of
      radiation therapy did not influence the risk of radiation therapy-associated
      adverse events in this cohort, which contradicts the commonly held clinical tenet
      that delaying radiation therapy reduces the risk of adverse events.

PMID- 25752389
TI  - Radiation therapy risk factors for development of lymphedema in patients treated
      with regional lymph node irradiation for breast cancer.
AB  - PURPOSE: We previously evaluated the risk of breast cancer-related lymphedema
      (LE) with the addition of regional lymph node irradiation (RLNR) and found an
      increased risk when RLNR is used. Here we analyze the association of technical
      radiation therapy (RT) factors in RLNR patients with the risk of LE development.
      METHODS AND MATERIALS: From 2005 to 2012, we prospectively screened 1476 women
      for LE who underwent surgery for breast cancer. Among 1507 breasts treated, 172
      received RLNR and had complete technical data for analysis. RLNR was delivered as
      supraclavicular (SC) irradiation (69% [118 of 172 patients]) or SC plus posterior
      axillary boost (PAB) (31% [54 of 172]). Bilateral arm volume measurements were
      performed pre- and postoperatively. Patients' RT plans were analyzed for SC field
      lateral border (relative to the humeral head), total dose to SC, RT fraction
      size, beam energy, and type of tangent (normal vs wide). Cox proportional hazards
      models were used to analyze associated risk factors for LE. RESULTS: Median
      postoperative follow-up was 29.3 months (range: 4.9-74.1 months). The 2-year
      cumulative incidence of LE was 22% (95% confidence interval [CI]: 15%-32%) for SC
      and 20% (95% CI: 11%-37%) for SC plus PAB (SC+PAB). None of the analyzed
      variables was significantly associated with LE risk (extent of humeral head:
      P=.74 for <1/3 vs >2/3, P=.41 for 1/3 to 2/3 vs >2/3; P=.40 for fraction size of
      1.8 Gy vs 2.0 Gy; P=.57 for beam energy 6 MV vs 10 MV; P=.74 for tangent type
      wide vs regular; P=.66 for SC vs SC+PAB). Only pretreatment body mass index
      (hazard ratio [HR]: 1.09; 95% CI: 1.04-1.15, P=.0007) and the use of axillary
      lymph node dissection (HR: 7.08, 95% CI: 0.98-51.40, P=.05) were associated with
      risk of subsequent LE development. CONCLUSIONS: Of the RT parameters tested, none
      was associated with an increased risk of LE development. This study underscores
      the need for future work investigating alternative RLNR risk factors for LE.

PMID- 25752390
TI  - Nodal stage of surgically resected non-small cell lung cancer and its effect on
      recurrence patterns and overall survival.
AB  - PURPOSE: Current National Comprehensive Cancer Network guidelines recommend
      postoperative radiation therapy (PORT) for patients with resected non-small cell
      lung cancer (NSCLC) with N2 involvement. We investigated the relationship between
      nodal stage and local-regional recurrence (LR), distant recurrence (DR) and
      overall survival (OS) for patients having an R0 resection. METHODS AND MATERIALS:
      A multi-institutional database of consecutive patients undergoing R0 resection
      for stage I-IIIA NSCLC from 1995 to 2008 was used. Patients receiving any
      radiation therapy before relapse were excluded. A total of 1241, 202, and 125
      patients were identified with N0, N1, and N2 involvement, respectively; 161
      patients received chemotherapy. Cumulative incidence rates were calculated for LR
      and DR as first sites of failure, and Kaplan-Meier estimates were made for OS.
      Competing risk analysis and proportional hazards models were used to examine LR,
      DR, and OS. Independent variables included age, sex, surgical procedure, extent
      of lymph node sampling, histology, lymphatic or vascular invasion, tumor size,
      tumor grade, chemotherapy, nodal stage, and visceral pleural invasion. RESULTS:
      The median follow-up time was 28.7 months. Patients with N1 or N2 nodal stage had
      rates of LR similar to those of patients with N0 disease, but were at
      significantly increased risk for both DR (N1, hazard ratio [HR] = 1.84, 95%
      confidence interval [CI]: 1.30-2.59; P=.001; N2, HR = 2.32, 95% CI: 1.55-3.48;
      P<.001) and death (N1, HR = 1.46, 95% CI: 1.18-1.81; P<.001; N2, HR = 2.33, 95%
      CI: 1.78-3.04; P<.001). LR was associated with squamous histology, visceral
      pleural involvement, tumor size, age, wedge resection, and segmentectomy. The
      most frequent site of LR was the mediastinum. CONCLUSIONS: Our investigation
      demonstrated that nodal stage is directly associated with DR and OS but not with
      LR. Thus, even some patients with, N0-N1 disease are at relatively high risk of
      local recurrence. Prospective identification of risk factors for local recurrence
      may aid in selecting an appropriate population for further study of postoperative
      radiation therapy.

PMID- 25752391
TI  - Safety and palliative efficacy of single-dose 8-Gy reirradiation for painful
      local failure in patients with stage IV non-small cell lung cancer previously
      treated with radical chemoradiation therapy.
AB  - PURPOSE: To investigate the safety and efficacy of single-dose 8-Gy palliative
      chest reirradiation (CRI) in metastatic non-small cell lung cancer (M-NSCLC)
      patients with painful thoracic failures (TF) within the previous radiation
      portal. PATIENTS AND METHODS: We retrospectively analyzed the clinical data of 78
      M-NSCLC patients who received single-dose 8-Gy CRI for painful TF after
      concurrent chemoradiation therapy to a total radiation dose of 52 to 66 Gy
      between 2007 and 2012. Primary endpoints included significant pain relief (SPR)
      defined as a >=2 point decrement in the Visual Analogue Scale for Pain inventory
      (VAS-P), time to pain relief, and duration of pain control. Secondary objectives
      were survival and prognostic factors. RESULTS: Treatment was well tolerated, with
      only 5.1% grade 3 pneumonitis and 1.3% grade 2 esophagitis. Pre-CRI median and
      post-CRI minimum VAS-P were 7 and 3 (P<.001), respectively. SPR was noted in 67
      (85.9%) patients, and only 3 (3.9%) scored progressive pain. Median time to
      lowest VAS-P and duration of pain control were 27 days and 6.1 months,
      respectively. Median overall survival (OS) was 7.7 months, and the 1-year OS rate
      was 26.5%. On multivariate analyses, lower Eastern Cooperative Oncology group
      score (1-2; P<.001), absence of anemia (P=.001), and fewer metastatic sites (1-2;
      P<.001) were found to be associated with longer OS. CONCLUSIONS: Single-dose 8-Gy
      CRI provides safe, effective, and durable pain palliation for TF in radically
      irradiated M-NSCLC patients. Because of its convenience, lower cost, and higher
      comfort, the present protocol can be considered an appropriate option for
      patients with limited life spans.

PMID- 25752392
TI  - Risk of hippocampal metastases in small cell lung cancer patients at presentation
      and after cranial irradiation: a safety profile study for hippocampal sparing
      during prophylactic or therapeutic cranial irradiation.
AB  - PURPOSE: Neurocognitive impairment (NI) in patients with small cell lung cancer
      (SCLC) after whole brain radiation treatment (WBRT) is a significant cause of
      morbidity. Hippocampal avoidance (HA) during WBRT may mitigate or prevent NI in
      such patients. However, this has not been tested in SCLC patients. The estimated
      risk of metastases in the HA region (HM) in patients with SCLC at diagnosis or
      after WBRT is unknown. Our study aimed to determine the risk of HM in patients
      with SCLC and to assess correlated clinical factors. METHODS AND MATERIALS:
      Patients with SCLC who experienced brain metastases (BM) at presentation (de
      novo) or after WBRT treated at the Saskatoon Cancer Centre between 2005 and 2012
      were studied. Relevant neuroimaging was independently reviewed by a
      neuroradiologist. HM was defined as metastases within 5 mm of the hippocampus.
      Logistic regression analysis was performed to assess correlation between various
      clinical variables and HM. RESULTS: Seventy eligible patients were identified. Of
      59 patients presenting with de novo BM, 3 patients (5%, 95% confidence interval
      [CI]: 0%-10.7%) had HM. Collectively there were 359 (range, 1-33) de novo BM with
      3 (0.8%, 95% CI: 0%-1.7%) HM deposits. Twenty patients experienced progression of
      metastatic disease in the brain after WBRT. Of the 20 patients, only 1 patient
      (5%, 95% CI: 0%-14.5%) experienced HM. On logistic regression, no factors
      significantly correlated with HM. CONCLUSION: The overall incidence of HM before
      or after WBRT in SCLC patients is low, providing preliminary support for the
      safety of HA during planned clinical trials of HA-WBRT for SCLC.

PMID- 25752394
TI  - Pudendal nerve and internal pudendal artery damage may contribute to radiation
      induced erectile dysfunction.
AB  - PURPOSE/OBJECTIVES: Erectile dysfunction is common after radiation therapy for
      prostate cancer; yet, the etiopathology of radiation-induced erectile dysfunction
      (RI-ED) remains poorly understood. A novel animal model was developed to study RI
      ED, wherein stereotactic body radiation therapy (SBRT) was used to irradiate the
      prostate, neurovascular bundles (NVB), and penile bulb (PB) of dogs. The purpose
      was to describe vascular and neurogenic injuries after the irradiation of only
      the NVB or the PB, and after irradiation of all 3 sites (prostate, NVB, and PB)
      with varying doses of radiation. METHODS AND MATERIALS: Dogs were treated with
      50, 40, or 30 Gy to the prostate, NVB, and PB, or 50 Gy to either the NVB or the
      PB, by 5-fraction SBRT. Electrophysiologic studies of the pudendal nerve and
      bulbospongiosus muscles and ultrasound studies of pelvic perfusion were performed
      before and after SBRT. The results of these bioassays were correlated with
      histopathologic changes. RESULTS: SBRT caused slowing of the systolic rise time,
      which corresponded to decreased arterial patency. Alterations in the response of
      the internal pudendal artery to vasoactive drugs were observed, wherein SBRT
      caused a paradoxical response to papaverine, slowing the systolic rise time after
      40 and 50 Gy; these changes appeared to have some dose dependency. The
      neurofilament content of penile nerves was also decreased at high doses and was
      more profound when the PB was irradiated than when the NVB was irradiated. These
      findings are coincident with slowing of motor nerve conduction velocities in the
      pudendal nerve after SBRT. CONCLUSIONS: This is the first report in which
      prostatic irradiation was shown to cause morphologic arterial damage that was
      coincident with altered internal pudendal arterial tone, and in which decreased
      motor function in the pudendal nerve was attributed to axonal degeneration and
      loss. Further investigation of the role played by damage to these structures in
      RI-ED is warranted.

PMID- 25752393
TI  - Molecular imaging biomarkers of resistance to radiation therapy for spontaneous
      nasal tumors in canines.
AB  - PURPOSE: Imaging biomarkers of resistance to radiation therapy can inform and
      guide treatment management. Most studies have so far focused on assessing a
      single imaging biomarker. The goal of this study was to explore a number of
      different molecular imaging biomarkers as surrogates of resistance to radiation
      therapy. METHODS AND MATERIALS: Twenty-two canine patients with spontaneous
      sinonasal tumors were treated with accelerated hypofractionated radiation
      therapy, receiving either 10 fractions of 4.2 Gy each or 10 fractions of 5.0 Gy
      each to the gross tumor volume. Patients underwent fluorodeoxyglucose (FDG)-,
      fluorothymidine (FLT)-, and Cu(II)-diacetyl-bis(N4-methylthiosemicarbazone) (Cu
      ATSM)-labeled positron emission tomography/computed tomography (PET/CT) imaging
      before therapy and FLT and Cu-ATSM PET/CT imaging during therapy. In addition to
      conventional maximum and mean standardized uptake values (SUV(max); SUV(mean))
      measurements, imaging metrics providing response and spatiotemporal information
      were extracted for each patient. Progression-free survival was assessed according
      to response evaluation criteria in solid tumor. The prognostic value of each
      imaging biomarker was evaluated using univariable Cox proportional hazards
      regression. Multivariable analysis was also performed but was restricted to 2
      predictor variables due to the limited number of patients. The best bivariable
      model was selected according to pseudo-R(2). RESULTS: The following variables
      were significantly associated with poor clinical outcome following radiation
      therapy according to univariable analysis: tumor volume (P=.011), midtreatment
      FLT SUV(mean) (P=.018), and midtreatment FLT SUV(max) (P=.006). Large decreases
      in FLT SUV(mean) from pretreatment to midtreatment were associated with worse
      clinical outcome (P=.013). In the bivariable model, the best 2-variable
      combination for predicting poor outcome was high midtreatment FLT SUV(max)
      (P=.022) in combination with large FLT response from pretreatment to midtreatment
      (P=.041). CONCLUSIONS: In addition to tumor volume, pronounced tumor
      proliferative response quantified using FLT PET, especially when associated with
      high residual FLT PET at midtreatment, is a negative prognostic biomarker of
      outcome in canine tumors following radiation therapy. Neither FDG PET nor Cu-ATSM
      PET were predictive of outcome.

PMID- 25752395
TI  - Coniferyl aldehyde reduces radiation damage through increased protein stability
      of heat shock transcriptional factor 1 by phosphorylation.
AB  - PURPOSE: We previously screened natural compounds and found that coniferyl
      aldehyde (CA) was identified as an inducer of HSF1. In this study, we further
      examined the protective effects of CA against ionizing radiation (IR) in normal
      cell system. METHODS AND MATERIALS: Western blotting and reverse transcription
      polymerase chain reaction tests were performed to evaluate expression of HSF1,
      HSP27, and HSP70 in response to CA. Cell death and cleavage of PARP and caspase-3
      were analyzed to determine the protective effects of CA in the presence of IR or
      taxol. The protective effects of CA were also evaluated using animal models.
      RESULTS: CA increased stability of the HSF1 protein by phosphorylation at Ser326,
      which was accompanied by increased expression of HSP27 and HSP70. HSF1
      phosphorylation at Ser326 by CA was mediated by EKR1/2 activation. Cotreatment of
      CA with IR or taxol in normal cells induced protective effects with
      phosphorylation- dependent patterns at Ser326 of HSF1. The decrease in bone
      marrow (BM) cellularity and increase of terminal deoxynucleotidyl transferase
      dUTP nick end labeling-positive BM cells by IR were also significantly inhibited
      by CA in mice (30.6% and 56.0%, respectively). A549 lung orthotopic lung tumor
      model indicated that CA did not affect the IR-mediated reduction of lung tumor
      nodules, whereas CA protected normal lung tissues from the therapeutic
      irradiation. CONCLUSIONS: These results suggest that CA may be useful for
      inducing HSF1 to protect against normal cell damage after IR or chemotherapeutic
      agents.

PMID- 25752396
TI  - Dependence of achievable plan quality on treatment technique and planning goal
      refinement: a head-and-neck intensity modulated radiation therapy application.
AB  - PURPOSE: To develop a practical workflow for retrospectively analyzing target and
      normal tissue dose-volume endpoints for various intensity modulated radiation
      therapy (IMRT) delivery techniques; to develop technique-specific planning goals
      to improve plan consistency and quality when feasible. METHODS AND MATERIALS: A
      total of 165 consecutive head-and-neck patients from our patient registry were
      selected and retrospectively analyzed. All IMRT plans were generated using the
      same dose-volume guidelines for TomoTherapy (Tomo, Accuray), TrueBeam (TB,
      Varian) using fixed-field IMRT (TB_IMRT) or RAPIDARC (TB_RAPIDARC), or Siemens
      Oncor (Siemens_IMRT, Siemens). A MATLAB-based dose-volume extraction and analysis
      tool was developed to export dosimetric endpoints for each patient. With a fair
      stratification of patient cohort, the variation of achieved dosimetric endpoints
      was analyzed among different treatment techniques. Upon identification of
      statistically significant variations, technique-specific planning goals were
      derived from dynamically accumulated institutional data. RESULTS: Retrospective
      analysis showed that although all techniques yielded comparable target coverage,
      the doses to the critical structures differed. The maximum cord doses were 34.1
      +/- 2.6, 42.7 +/- 2.1, 43.3 +/- 2.0, and 45.1 +/- 1.6 Gy for Tomo, TB_IMRT,
      TB_RAPIDARC, and Siemens_IMRT plans, respectively. Analyses of variance showed
      significant differences for the maximum cord doses but no significant differences
      for other selected structures among the investigated IMRT delivery techniques.
      Subsequently, a refined technique-specific dose-volume guideline for maximum cord
      dose was derived at a confidence level of 95%. The dosimetric plans that failed
      the refined technique-specific planning goals were reoptimized according to the
      refined constraints. We observed better cord sparing with minimal variations for
      the target coverage and other organ at risk sparing for the Tomo cases, and
      higher parotid doses for C-arm linear accelerator-based IMRT and RAPIDARC plans.
      CONCLUSION: Patient registry-based processes allowed easy and systematic
      dosimetric assessment of treatment plan quality and consistency. Our analysis
      revealed the dependence of certain dosimetric endpoints on the treatment
      techniques. Technique-specific refinement of planning goals may lead to
      improvement in plan consistency and plan quality.

PMID- 25752397
TI  - Accuracy of routine treatment planning 4-dimensional and deep-inspiration breath
      hold computed tomography delineation of the left anterior descending artery in
      radiation therapy.
AB  - PURPOSE: To assess the feasibility of radiation therapy treatment planning 4
      dimensional computed tomography (4DCT) and deep-inspiration breath-hold (DIBH) CT
      to accurately contour the left anterior descending artery (LAD), a primary
      indicator of radiation-induced cardiac toxicity for patients undergoing radiation
      therapy. METHODS AND MATERIALS: Ten subjects were prospectively imaged with a
      cardiac-gated MRI protocol to determine cardiac motion effects, including the
      displacement of a region of interest comprising the LAD. A series of planar views
      were obtained and resampled to create a 3-dimensional (3D) volume. A 3D optical
      flow deformable image registration algorithm determined tissue displacement
      during the cardiac cycle. The measured motion was then used as a spatial boundary
      to characterize motion blurring of the radiologist-delineated LAD structure for a
      cohort of 10 consecutive patients enrolled prospectively on a breast study
      including 4DCT and DIBH scans. Coronary motion-induced blurring artifacts were
      quantified by applying an unsharp filter to accentuate the LAD structure despite
      the presence of motion blurring. The 4DCT maximum inhalation and exhalation
      respiratory phases were coregistered to determine the LAD displacement during
      tidal respiration, as visualized in 4DCT. RESULTS: The average 90th percentile
      heart motion for the region of interest was 0.7 +/- 0.1 mm (left-right [LR]), 1.3
      +/- 0.6 mm (superior-inferior [SI]), and 0.6 +/- 0.2 mm (anterior-posterior [AP])
      in the cardiac-gated MRI cohort. The average relative increase in the number of
      voxels comprising the LAD contour was 69.4% +/- 4.5% for the DIBH. The LAD volume
      overestimation had the dosimetric impact of decreasing the reported mean LAD dose
      by 23% +/- 9% on average in the DIBH. During tidal respiration the average
      relative LAD contour increase was 69.3% +/- 5.9% and 67.9% +/- 4.6% for
      inhalation and exhalation respiratory phases, respectively. The average 90th
      percentile LAD motion was 4.8 +/- 1.1 mm (LR), 0.9 +/- 0.4 mm (SI), and 1.9 +/-
      0.6 mm (AP) for the 4DCT cohort, in the absence of cardiac gating. CONCLUSIONS:
      An anisotropic margin of 2.7 mm (LR), 4.1 mm (SI), and 2.4 mm (AP) was
      quantitatively determined to account for motion blurring and patient setup error
      while placing minimum constraint on the plan optimization.

PMID- 25752398
TI  - Pelvic nodal dosing with registration to the prostate: implications for high-risk
      prostate cancer patients receiving stereotactic body radiation therapy.
AB  - PURPOSE: To determine whether image guidance with rigid registration (RR) to
      intraprostatic markers (IPMs) yields acceptable coverage of the pelvic lymph
      nodes in the context of a stereotactic body radiation therapy (SBRT) regimen.
      METHODS AND MATERIALS: Four to seven kilovoltage cone-beam CTs (CBCTs) from 12
      patients with high-risk prostate cancer were analyzed, allowing approximation of
      an SBRT regimen. The nodal clinical target volume (CTV(N)) and bladder were
      contoured on all kilovoltage CBCTs. The V100 CTV(N), expressed as a ratio to the
      same parameter on the initial plan, and the magnitude of translational shift
      between RR to the IPMs versus RR to the pelvic bones, were computed. The ability
      of a multimodality bladder filling protocol to minimize bladder height variation
      was assessed in a separate cohort of 4 patients. RESULTS: Sixty-five CBCTs were
      assessed. The average V100 CTV(N) was 92.6%, but for a subset of 3 patients the
      average was 80.0%, compared with 97.8% for the others (P<.0001). The average
      overall and superior-inferior axis magnitudes of the bony-to-fiducial
      translations were significantly larger in the subgroup with suboptimal nodal
      coverage (8.1 vs 3.9 mm and 5.8 vs 2.4 mm, respectively; P<.0001). Relative
      bladder height changes were also significantly larger in the subgroup with
      suboptimal nodal coverage (42.9% vs 18.5%; P<.05). Use of a multimodality bladder
      filling protocol minimized bladder height variation (P<.001). CONCLUSION: A
      majority of patients had acceptable nodal coverage after RR to IPMs, even when
      approximating SBRT. However, a subset of patients had suboptimal nodal coverage.
      These patients had large bony-to-fiducial translations and large variations in
      bladder height. Nodal coverage should be excellent if the superior-inferior axis
      bony-to-fiducial translation and the relative bladder height change (both easily
      measured on CBCT) are kept to a minimum. Implementation of a strict bladder
      filling protocol may achieve this goal.

PMID- 25752399
TI  - Magnetic resonance imaging-guided versus surrogate-based motion tracking in liver
      radiation therapy: a prospective comparative study.
AB  - PURPOSE: This study applied automatic feature detection on cine-magnetic
      resonance imaging (MRI) liver images in order to provide a prospective comparison
      between MRI-guided and surrogate-based tracking methods for motion-compensated
      liver radiation therapy. METHODS AND MATERIALS: In a population of 30 subjects (5
      volunteers plus 25 patients), 2 oblique sagittal slices were acquired across the
      liver at high temporal resolution. An algorithm based on scale invariant feature
      transform (SIFT) was used to extract and track multiple features throughout the
      image sequence. The position of abdominal markers was also measured directly from
      the image series, and the internal motion of each feature was quantified through
      multiparametric analysis. Surrogate-based tumor tracking with a state-of-the-art
      external/internal correlation model was simulated. The geometrical tracking error
      was measured, and its correlation with external motion parameters was also
      investigated. Finally, the potential gain in tracking accuracy relying on MRI
      guidance was quantified as a function of the maximum allowed tracking error.
      RESULTS: An average of 45 features was extracted for each subject across the
      whole liver. The multi-parametric motion analysis reported relevant inter- and
      intrasubject variability, highlighting the value of patient-specific and
      spatially-distributed measurements. Surrogate-based tracking errors (relative to
      the motion amplitude) were were in the range 7% to 23% (1.02-3.57 mm) and were
      significantly influenced by external motion parameters. The gain of MRI guidance
      compared to surrogate-based motion tracking was larger than 30% in 50% of the
      subjects when considering a 1.5-mm tracking error tolerance. CONCLUSIONS:
      Automatic feature detection applied to cine-MRI allows detailed liver motion
      description to be obtained. Such information was used to quantify the performance
      of surrogate-based tracking methods and to provide a prospective comparison with
      respect to MRI-guided radiation therapy, which could support the definition of
      patient-specific optimal treatment strategies.

PMID- 25752400
TI  - MRI-based computed tomography metal artifact correction method for improving
      proton range calculation accuracy.
AB  - PURPOSE: Computed tomography (CT) artifacts can severely degrade dose calculation
      accuracy in proton therapy. Prompted by the recently increased popularity of
      magnetic resonance imaging (MRI) in the radiation therapy clinic, we developed an
      MRI-based CT artifact correction method for improving the accuracy of proton
      range calculations. METHODS AND MATERIALS: The proposed method replaces corrupted
      CT data by mapping CT Hounsfield units (HU number) from a nearby artifact-free
      slice, using a coregistered MRI. MRI and CT volumetric images were registered
      with use of 3-dimensional (3D) deformable image registration (DIR). The
      registration was fine-tuned on a slice-by-slice basis by using 2D DIR. Based on
      the intensity of paired MRI pixel values and HU from an artifact-free slice, we
      performed a comprehensive analysis to predict the correct HU for the corrupted
      region. For a proof-of-concept validation, metal artifacts were simulated on a
      reference data set. Proton range was calculated using reference, artifactual, and
      corrected images to quantify the reduction in proton range error. The correction
      method was applied to 4 unique clinical cases. RESULTS: The correction method
      resulted in substantial artifact reduction, both quantitatively and
      qualitatively. On respective simulated brain and head and neck CT images, the
      mean error was reduced from 495 and 370 HU to 108 and 92 HU after correction.
      Correspondingly, the absolute mean proton range errors of 2.4 cm and 1.7 cm were
      reduced to less than 2 mm in both cases. CONCLUSIONS: Our MRI-based CT artifact
      correction method can improve CT image quality and proton range calculation
      accuracy for patients with severe CT artifacts.

PMID- 25752401
TI  - Individualized positron emission tomography-based isotoxic accelerated radiation
      therapy is cost-effective compared with conventional radiation therapy: a model
      based evaluation.
AB  - PURPOSE: To evaluate long-term health effects, costs, and cost-effectiveness of
      positron emission tomography (PET)-based isotoxic accelerated radiation therapy
      treatment (PET-ART) compared with conventional fixed-dose CT-based radiation
      therapy treatment (CRT) in non-small cell lung cancer (NSCLC). METHODS AND
      MATERIALS: Our analysis uses a validated decision model, based on data of 200
      NSCLC patients with inoperable stage I-IIIB. Clinical outcomes, resource use,
      costs, and utilities were obtained from the Maastro Clinic and the literature.
      Primary model outcomes were the difference in life-years (LYs), quality-adjusted
      life-years (QALYs), costs, and the incremental cost-effectiveness and
      cost/utility ratio (ICER and ICUR) of PET-ART versus CRT. Model outcomes were
      obtained from averaging the predictions for 50,000 simulated patients. A
      probabilistic sensitivity analysis and scenario analyses were carried out.
      RESULTS: The average incremental costs per patient of PET-ART were ?569 (95%
      confidence interval [CI] ?-5327-?6936) for 0.42 incremental LYs (95% CI 0.19
      0.61) and 0.33 QALYs gained (95% CI 0.13-0.49). The base-case scenario resulted
      in an ICER of ?1360 per LY gained and an ICUR of ?1744 per QALY gained. The
      probabilistic analysis gave a 36% probability that PET-ART improves health
      outcomes at reduced costs and a 64% probability that PET-ART is more effective at
      slightly higher costs. CONCLUSION: On the basis of the available data,
      individualized PET-ART for NSCLC seems to be cost-effective compared with CRT.

PMID- 25752402
TI  - Incorporating cancer stem cells in radiation therapy treatment response modeling
      and the implication in glioblastoma multiforme treatment resistance.
AB  - PURPOSE: To perform a preliminary exploration with a simplistic mathematical
      cancer stem cell (CSC) interaction model to determine whether the tumor-intrinsic
      heterogeneity and dynamic equilibrium between CSCs and differentiated cancer
      cells (DCCs) can better explain radiation therapy treatment response with a dual
      compartment linear-quadratic (DLQ) model. METHODS AND MATERIALS: The
      radiosensitivity parameters of CSCs and DCCs for cancer cell lines including
      glioblastoma multiforme (GBM), non-small cell lung cancer, melanoma,
      osteosarcoma, and prostate, cervical, and breast cancer were determined by
      performing robust least-square fitting using the DLQ model on published
      clonogenic survival data. Fitting performance was compared with the single
      compartment LQ (SLQ) and universal survival curve models. The fitting results
      were then used in an ordinary differential equation describing the kinetics of
      DCCs and CSCs in response to 2- to 14.3-Gy fractionated treatments. The total
      dose to achieve tumor control and the fraction size that achieved the least
      normal biological equivalent dose were calculated. RESULTS: Smaller cell survival
      fitting errors were observed using DLQ, with the exception of melanoma, which had
      a low alpha/beta = 0.16 in SLQ. Ordinary differential equation simulation
      indicated lower normal tissue biological equivalent dose to achieve the same
      tumor control with a hypofractionated approach for 4 cell lines for the DLQ
      model, in contrast to SLQ, which favored 2 Gy per fraction for all cells except
      melanoma. The DLQ model indicated greater tumor radioresistance than SLQ, but the
      radioresistance was overcome by hypofractionation, other than the GBM cells,
      which responded poorly to all fractionations. CONCLUSION: The distinct
      radiosensitivity and dynamics between CSCs and DCCs in radiation therapy response
      could perhaps be one possible explanation for the heterogeneous intertumor
      response to hypofractionation and in some cases superior outcome from
      stereotactic ablative radiation therapy. The DLQ model also predicted the
      remarkable GBM radioresistance, a result that is highly consistent with clinical
      observations. The radioresistance putatively stemmed from accelerated DCC
      regrowth that rapidly restored compartmental equilibrium between CSCs and DCCs.

PMID- 25752403
TI  - In regard to Morganti et al.

PMID- 25752404
TI  - In reply to Yamazaki et al.

PMID- 25752405
TI  - In regard to Zhou et al.

PMID- 25752406
TI  - In reply to Abbasi et al.

PMID- 25752407
TI  - In regard to Holliday et al.

PMID- 25752408
TI  - In reply to Lo et al.

PMID- 25752409
TI  - In regard to Dyk et al.

PMID- 25752410
TI  - Erratum to: Hindley A, Zain Z, Wood L, et al. Mometasone furoate cream reduces
      acute radiation dermatitis in patients receiving breast radiation therapy:
      results of a randomized trial. Int J Radiat Oncol Biol Phys 2014;90:748-755.

PMID- 25752414
TI  - The stroke care revolution.

PMID- 25752415
TI  - Delayed diagnosis of late-onset Pompe disease in patients with myopathies of
      unknown origin and/or hyperCKemia.
AB  - Pompe disease is a rare metabolic myopathy whose diagnosis is sometimes delayed
      despite being essential for improving clinical outcomes. We aimed to investigate
      the prevalence of late-onset Pompe disease among patients with a myopathy of
      unknown etiology, including polymyositis, or with idiopathic rise of creatine
      kinase (CK) levels, in a department of internal medicine. A cohort study was
      conducted in 241 subjects: 140 patients with myopathies of unknown origin or
      increased CK levels, 30 with polymyositis and 71 who constituted the control
      group of other myopathies. Acid alpha-glucosidase (GAA) activity was tested in
      dried blood spots. If a positive result was obtained, GAA activity in isolated
      lymphocytes and/or genetic testing was performed as a confirmatory diagnosis. Out
      of the 140 investigated patients, 2 patients with myopathies of unknown origin
      were confirmed to be positive for Pompe disease. Thus, late-onset Pompe disease
      should be considered among adult patients with myopathy of unknown origin. 

PMID- 25752416
TI  - Chlamydia-secreted protease CPAF degrades host antimicrobial peptides.
AB  - Chlamydia trachomatis infection in the lower genital tract, if untreated, can
      ascend to the upper genital tract, potentially leading to complications such as
      tubal factor infertility. The ascension involves cell-to-cell spreading, which
      may require C. trachomatis organisms to overcome mucosal extracellular effectors
      such as antimicrobial peptides. We found that among the 8 antimicrobial peptides
      tested, the cathelicidin LL-37 that is produced by both urogenital epithelial
      cells and the recruited neutrophils possessed a most potent antichlamydial
      activity. Interestingly, this antichlamydial activity was completely inhibited by
      CPAF, a C. trachomatis-secreted serine protease. The inhibition was dependent on
      CPAF's proteolytic activity. CPAF selectively degraded LL-37 and other
      antimicrobial peptides with an antichlamydial activity. CPAF is known to secrete
      into and accumulate in the infected host cell cytoplasm at the late stage of
      chlamydial intracellular growth and may be released to confront the extracellular
      antimicrobial peptides before the intra-inclusion organisms are exposed to
      extracellular environments during host cell lysis and chlamydial spreading. Thus,
      the finding that CPAF selectively targets host antimicrobial peptides that
      possess antichlamydial activities for proteolysis suggests that CPAF may
      contribute to C. trachomatis pathogenicity by aiding in ascending infection. 

PMID- 25752417
TI  - Benefits of Completion 3D Angiography Associated with Contrast Enhanced
      Ultrasound to Assess Technical Success after EVAR.
AB  - OBJECTIVES: This study evaluated a new strategy to assess technical success after
      standard and complex endovascular aortic repair (EVAR), combining completion
      contrast enhanced cone beam computed tomography (ceCBCT) and post-operative
      contrast enhanced ultrasound (CEUS). METHODS: Patients treated with bifurcated or
      fenestrated and branched endografts in the hybrid room during the study period
      were included. From December 2012 to July 2013, a completion angiogram (CA) was
      performed at the end of the procedure, and computed tomography angiography (CTA)
      before discharge (group 1). From October 2013 to April 2014, a completion ceCBCT
      was performed, followed by CEUS during the 30 day post-operative period (group
      2). The rate of peri-operative events (type I or III endoleaks, kinks, occlusion
      of target vessels), need for additional procedures or early secondary procedures,
      total radiation exposure (mSv), and total volume of contrast medium injected were
      compared. RESULTS: Seventy-nine patients were included in group 1 and 54 in group
      2. Peri-operative event rates were respectively 8.9% (n = 7) and 33.3% (n = 18)
      (p = .001). Additional procedures were performed in seven patients (8.9%) in
      group 1 versus 17 (31.5%) in group 2 (p = .001). Two early secondary procedures
      were performed in group 2 (3.7%), and three (3.8%) in group 1 (p = .978). Median
      radiation exposure due to CBCT was 7 Gy cm(2) (5.25-8) (36%, 27%, and 9% of the
      total procedure exposure, respectively for bifurcated, fenestrated, and branched
      endografts). CEUS did not diagnose endoleaks or any adverse events not diagnosed
      by ceCBCT. Overall radiation and volume of contrast injected during the patient
      hospital stay in groups 1 and 2 were 34 (25.8-47.3) and 11 (5-20.5) mSv, and 184
      (150-240) and 91 (70-132.8) mL respectively (reduction of 68% and 50%, p < .001).
      CONCLUSIONS: Completion ceCBCT is achievable in routine practice to assess
      technical success after EVAR. Strategies to evaluate technical success combining
      ceCBCT and CEUS can reduce total in hospital radiation exposure and contrast
      medium volume injection.

PMID- 25752418
TI  - Dual antiplatelet therapy after carotid stenting: lessons from 'big brother'.

PMID- 25752419
TI  - Regional Differences in Case Mix and Peri-operative Outcome After Elective
      Abdominal Aortic Aneurysm Repair in the Vascunet Database.
AB  - OBJECTIVE/BACKGROUND: National differences exist in the outcome of elective
      abdominal aortic aneurysm (AAA) repair. The role of case mix variation was
      assessed based on an international vascular registry collaboration. METHODS: All
      elective AAA repairs with aneurysm size data in the Vascunet database in the
      period 2005-09 were included. AAA size and peri-operative outcome (crude and age
      adjusted mortality) were analysed overall and in risk cohorts, as well as per
      country. Glasgow Aneurysm Score (GAS) was calculated as risk score, and patients
      were stratified in three equal sized risk cohorts based on GAS. Predictors of
      peri-operative mortality were analysed with multiple regression. Missing data
      were handled with multiple imputation. RESULTS: Patients from Australia, Finland,
      Hungary, Norway, Sweden and the UK (n = 5,895) were analysed; mean age was 72.7
      years and 54% had endovascular repair (EVAR). There were significant variations
      in GAS (lowest = Finland [75.7], highest = UK [79.4], p for comparison of all
      regions < .001), proportion of AAA < 5.5 cm (lowest = UK [6.4%], highest =
      Hungary [29.0%]; p < .001), proportion undergoing EVAR (lowest = Finland [10.1%],
      highest = Australia [58.9%]; p < .001), crude mortality (lowest = Norway [2.0%],
      highest = Finland [5.0%]; p = .006), and age adjusted mortality (lowest = Norway
      [2.5%], highest = Finland [6.0%]; p = .048). Both aneurysm size and peri
      operative mortality were highest among patients with a GAS >82. Of those with a
      GAS >82, 8.4% of men and 20.8% of women had an AAA <5.5 cm. CONCLUSION: Important
      regional differences exist in case selection for elective AAA repair, including
      variations in AAA size and patient risk profile. These differences partly explain
      the variations in peri-operative mortality. Further audit is warranted to assess
      the underlying reasons for the regional variation in case-mix.

PMID- 25752420
TI  - Should I Treat Asymptomatic Thrombus Lining an EVAR Stent Graft Limb Detected
      During Surveillance Imaging and, if so, How?

PMID- 25752421
TI  - Giant true brachial artery aneurysm after hemodialysis fistula closure.

PMID- 25752422
TI  - Synthesis and evaluation of tetrahydroindazole derivatives as sigma-2 receptor
      ligands.
AB  - A series of tetrahydroindazole derivatives were synthesized and evaluated for
      their affinities for both sigma-1 and sigma-2 receptors. These compounds are
      hybrid structures of a tetrahydroindazole substituted benzamide and a 6,7
      dimethoxy-1,2,3,4-tetrahydroisoquinoline moiety or a 9-azabicyclo[3.3.1]nonan-3
      yl-amine moiety. These newly synthesized hybrid analogs showed various affinities
      for sigma-2 receptor without any significant affinities for sigma-1 receptor. In
      particular, compounds 12, 15b, 15c, and 15d, demonstrated moderate affinity and
      excellent selectivity for sigma-2 receptor. It is interesting to note that 3-5
      carbon units between the tetrahydroindazole substituted benzamide and the 6,7
      dimethoxy-1,2,3,4-tetrahydroisoquinoline moiety are appropriate for sigma-2
      receptor binding. No substitution on the 9-aza nitrogen is proper for sigma-2
      affinity in the 2-(9-azabicyclo[3.3.1]nonan-3-yl-amino)-4-(3,6,6-trimethyl-4-oxo
      4,5,6,7-tetrahydro-1H-indazol-1-yl)benzamide analogs. 

PMID- 25752423
TI  - Purification and characterization of a Kunitz inhibitor from Poincianella
      pyramidalis with insecticide activity against the Mediterranean flour moth.
AB  - This paper describes the characterization of a trypsin inhibitor from
      Poincianella pyramidalis seeds (PpyTI). The partial sequencing of PpyTI revealed
      homology to Kunitz inhibitors, clustered as a member of Family I03 in MEROPS
      database. PpyTI has a single polypeptide chain of 19,042 Da and presents
      stability at high temperatures (up to 70  degrees C) and a wide range of pH. In
      vitro assays showed that disulfide bridges have an important stabilization role
      of reactive site in PpyTI, a characteristic shared among several Kunitz
      inhibitors. Bioassays carried out with the Mediterranean flour moth (Anagasta
      kuehniella) revealed a significant decrease in both larval weight and survival of
      PpyTI-fed larvae, besides a larval stage extension. Through biochemical analysis,
      we demonstrated that the PpyTI insecticide effects were triggered by digestion
      process commitment, through the inhibition of trypsin and chymotrypsin
      activities, the major digestive enzymes in this species. The insecticide effects
      and biochemical characterization of PpyTI encourage further studies using this
      inhibitor for insect pest control.

PMID- 25752424
TI  - Fipronil induced oxidative stress in kidney and brain of mice: protective effect
      of vitamin E and vitamin C.
AB  - Fipronil is a relatively new insecticide of the phenpyrazole group. Fipronil
      induced effects on antioxidant system and oxidative stress biomarkers are yet to
      be studied in vivo. The present study was undertaken to evaluate fipronil-induced
      alterations in the blood biochemical markers and tissue antioxidant enzymes after
      oral exposure in mice and to explore possible protective effect of pre-treatment
      of antioxidant vitamins against these alterations. Mice were divided into eight
      groups containing control, test and amelioration groups. Mice in the test groups
      were exposed to different doses of fipronil, i.e., 2.5, 5 and 10 mg/kg bw,
      respectively for 28 days. Mice in the amelioration groups were treated with
      vitamin E or vitamin C (each at 100 mg/kg) 2 h prior to high dose (10 mg/kg) of
      fipronil. Fipronil exposure at three doses caused significant increase in the
      blood biochemical markers, lipid peroxidation and prominent histopathological
      alterations; while level of antioxidant enzymes was severely decreased both in
      kidney and brain tissues. Prior administration of vitamin E or vitamin C in the
      fipronil exposed mice led to decrease in lipid peroxidation and significant
      increase in activities of antioxidants, viz., glutathione, total thiol,
      superoxide dismutase and catalase. Vitamin E and vitamin C administration in
      fipronil exposed mice also improved histological architecture of the kidney and
      brain when compared with fipronil alone treated groups. Thus, results of the
      present study demonstrated that in vivo fipronil exposure induces oxidative
      stress and pre-treatment with vitamin E or C can protect mice against this
      oxidative insult.

PMID- 25752425
TI  - Naturally produced citral can significantly inhibit normal physiology and induce
      cytotoxicity on Magnaporthe grisea.
AB  - Given the importance of finding alternatives to synthetic fungicides, the
      antifungal effects of natural product citral on six plant pathogenic fungi
      (Magnaporthe grisea, Gibberella zeae, Fusarium oxysporum, Valsa mali, Botrytis
      cinerea, and Rhizoctonia solani) were determined. Mycelial growth rate results
      showed that citral possessed high antifungal activities on those test fungi with
      EC50 values ranging from 39.52 to 193.00 ug/mL, which had the highest inhibition
      rates against M. grisea. Further action mechanism of citral on M. grisea was
      carried out. Citral treatment was found to alter the morphology of M. grisea
      hyphae by causing a loss of cytoplasm and distortion of mycelia. Moreover, citral
      was able to induce an increase in chitinase activity in M. grisea, indicating
      disruption of the cell wall. These results indicate that citral may act by
      disrupting cell wall integrity and membrane permeability, thus resulting in
      physiology changes and causing cytotoxicity. Importantly, the inhibitory effect
      of citral on M. grisea appears to be associated with its effects on mycelia
      reducing sugar, soluble protein, chitinase activity, pyruvate content, and
      malondialdehyde content.

PMID- 25752426
TI  - Isolation and purification of a papain inhibitor from Egyptian genotypes of
      barley seeds and its in vitro and in vivo effects on the cowpea bruchid,
      Callosobruchus maculatus (F.).
AB  - The cysteine inhibitors that are known as cystatin have been identified and
      characterized from several plant species. In the current study, 44 barley
      (Hordeum vulgare) genotypes including 3 varieties and 41 promising lines were
      screened for their potential as protease inhibitors. The barley genotypes showed
      low inhibitory activity against trypsin and chymotrypsin enzymes with a mean of
      4.15 TIU/mg protein and 4.40 CIU/mg protein. The barley variety, Giza 123, showed
      strong papain inhibitory activity of 97.09 PIU/mg proteins and was subjected for
      further purification studies using ammonium sulfate fractionation and DEAE
      Sephadex A-25 column. Barley purified proteins showed two bands on SDS-PAGE
      corresponding to a molecular mass of 12.4-54.8 kDa. The purified barley PI was
      found to be stable at a temperature below 80  degrees C and at a wide range of pH
      from 2 to 12. Barley PI was found to have higher potential inhibitory activity
      against papain enzyme compared to the standard papain inhibitor, E-64 with an
      IC50 value of 21.04 ug/ml and 25.62 ug/ml for barley PI and E-64, respectively.
      The kinetic analysis revealed a non-competitive type of inhibition with a Ki
      value of 1.95 * 10(-3 )uM. The antimetabolic effect of barley PI was evaluated
      against C. maculatus by incorporating the F30-60 protein of the purified
      inhibitor into the artificial diet using artificial seeds. Barley PI
      significantly prolonged the development of C. maculatus in proportion to PI
      concentration. Barley PI significantly increased the mortality of C. maculatus
      and caused a significant reduction in its fecundity. On the other hand, barley PI
      seemed to have non-significant effects on the adult longevity and the adult dry
      weight. The in vitro and in vivo results proved the efficiency of the papain
      inhibitory protein isolated from barley as a tool for managing the cowpea
      bruchid, C. maculatus.

PMID- 25752427
TI  - Biodegradation of pesticide triclosan by A. versicolor in simulated wastewater
      and semi-synthetic media.
AB  - Triclosan is known as an antimicrobial agent, a powerful bacteriostat and an
      important pesticide. In this paper biodegradation of triclosan by Aspergillus
      versicolor was investigated. Effects of simulated wastewater and semi-synthetic
      media on fungal triclosan degradation process were detected. HPLC analysis showed
      that fungal triclosan biodegradation yield was 71.91% at about 7.5 mg/L
      concentration in semi-synthetic medium and was 37.47% in simulated wastewater.
      Fungus could be able to tolerate the highest triclosan concentration (15.69
      mg/L). The biodegradation yield was 29.81% and qm was 2.22 mg/g at this
      concentration. Some of the parameters, such as pH, culture media, increasing
      triclosan and biomass concentrations were optimized in order to achieve the
      effective triclosan biodegradation process. The highest triclosan biodegradation
      yields of all microorganisms were achieved by A. versicolor.

PMID- 25752428
TI  - Determination of genotoxic effects of Imazethapyr herbicide in Allium cepa root
      cells by mitotic activity, chromosome aberration, and comet assay.
AB  - Imazethapyr (IM) is an imidazolinone herbicide that is currently used for broad
      spectrum weed control in soybean and other legume crops. In this study, cytotoxic
      and genotoxic effects of IM were investigated by using mitotic index (MI),
      mitotic phases, chromosomal abnormalities (CAs) and DNA damage on the root
      meristem cells of Allium cepa. In Allium root growth inhibition test, EC50 value
      was determined as 20 ppm, and 0.5xEC50, EC50 and 2xEC50 concentrations of IM
      herbicide were introduced to onion tuber roots. Distilled water and methyl
      methane sulfonate (MMS, 10 mg/L) were used as a negative and positive control,
      respectively. As A. cepa cell cycle is 24 hours, so, application process was
      carried out for 24, 48, 72 and 96 hours. All the applied doses decreased MIs
      compared to control group and these declines were found to be statistically
      meaningful. Analysis of the chromosomes showed that 10 ppm IM except for 48 h
      induced CAs but 40 ppm IM except for 72 h decreased CAs. DNA damage was found
      significantly higher in 20 and 40 ppm of IM compared to the control in comet
      assay. These results indicated that IM herbicide exhibits cytotoxic activity but
      not genotoxic activity (except 10 ppm) and induced DNA damage in a dose dependent
      manner in A. cepa root meristematic cells.

PMID- 25752429
TI  - Oxidative stress in human erythrocytes treated with bromfenvinphos and its
      impurities.
AB  - Bromfenvinphos (BFVF) is an organophosphorus (OP) pesticide which was widely used
      in agriculture and veterinary practice. During synthesis of this insecticide five
      main impurities are formed: dihydro-bromfenvinphos, dibromo-bromfenvinphos, 2,4
      dichlorophenacyl bromide, 2,4-dichlorophenacylidene bromide and 2,4
      dichlorophenacylidyne bromide, which can be present in technical grade
      bromfenvinphos in amounts from 0.1 to 4%. The aim of this study was to examine
      the influence of bromfenvinphos and its manufacturing impurities on parameters of
      oxidative stress, the activity of antioxidative enzymes and the level of reduced
      glutathione. Human erythrocytes were incubated with bromfenvinphos and its
      impurities in the concentrations range from 0.5 to 500 uM for 1 h. This study
      indicated that 2,4-dichlorophenacyl derivatives more strongly oxidized analyzed
      parameters in human erythrocytes than bromfenvinphos. Investigated compounds
      caused an increase in lipid peroxidation and oxidation of fluorescent probe DCFH2
      - the strongest pro-oxidative changes were provoked by 2,4-dichlorophenacyl
      bromide. None of the compounds studied in the concentrations from 0.5 to 500 uM
      changed the activity of SOD and only 2,4-dichlorophenacyl decreased activity of
      CAT. The level of GSH was only altered by 2,4-dichlorophenacyl derivatives. It
      was observed that increasing number of bromine atoms in the side chain of those
      derivatives was associated with decreased GSH level.

PMID- 25752430
TI  - The effects of triazophos applied to transgenic Bt rice on the nutritional
      indexes, Nlvg expression, and population growth of Nilaparvata lugens Stal under
      elevated CO2.
AB  - The brown planthopper, Nilaparvata lugens (Stal) (Hemiptera: Delphacidae), is a
      typical pest in which population resurgence can be induced by insecticides.
      Warmer global temperatures, associated with anthropogenic climate change, are
      likely to have marked ecological effects on terrestrial ecosystems. However, the
      effects of elevated CO2 (eCO2) concentrations on the resurgence of N. lugens that
      have been treated with pesticides used for transgenic Bt rice cultivation are not
      fully understood. The present study investigated changes in the protein content,
      soluble sugar content, free amino acid level, vitellogenin (Nlvg) mRNA
      expression, and the population growth of N. lugens on transgenic Bt rice (TT51)
      following triazaophos foliar spray under conditions of eCO2. The results showed
      that the protein content in the fat bodies and ovaries of N. lugens adult females
      in TT51 treated with 40 ppm triazophos under eCO2 was significantly higher than
      under ambient CO2 (aCO2) and was also higher than that in females feeding on the
      non-transgenic parent (MH63) under aCO2 at different days after emergence (DAEs).
      The soluble sugar content and free amino level of adult females in TT51 treated
      with 40 ppm triazophos under eCO2 was significantly higher than under aCO2 and
      was also higher than in MH63 under aCO2 at 1 and 3 DAE. The Nlvg mRNA expression
      level of N. lugens adult females in TT51 treated with 40 ppm triazophos under
      eCO2 was significantly higher than under aCO2 and was also higher than in MH63
      under aCO2 at 1 and 3 DAE. The population number of N. lugens in TT51 treated
      with 40 ppm triazophos under eCO2 was significantly higher than under aCO2 and
      was also higher than in MH63 under aCO2. The present findings provide important
      information for integrated pest management with transgenic varieties and a better
      understanding of the resurgence mechanism of N. lugens under eCO2.

PMID- 25752431
TI  - Effects of prometryne on early life stages of common carp (Cyprinus carpio L.).
AB  - Toxicity of prometryne to early life stages of common carp was assessed. On the
      basis of accumulated mortality in the experimental groups lowest observed-effect
      concentration (LOEC) was estimated as 1100 ug/l; and no observed-effect
      concentration (NOEC) was 850 ug/l. Fulton's condition factor was significantly
      lower than in controls in fish exposed to 4000 ug/l after 7, 14, and 21 days. By
      day 14, fish exposed to 4000 ug/l prometryne showed significantly lower mass and
      total length compared to controls. Fish exposed the 1200 and 4000 ug/l showed
      delay in development, severe hyperaemia in gill, liver, and caudal and cranial
      kidney. Subchronic prometryne exposure of early-life stages of common carp at
      concentrations of 1200 and 4000 ug/l affected their survival, growth rate, early
      ontogeny, and histology.

PMID- 25752432
TI  - Eugenol-inhibited root growth in Avena fatua involves ROS-mediated oxidative
      damage.
AB  - Plant essential oils and their constituent monoterpenes are widely known plant
      growth retardants but their mechanism of action is not well understood. We
      explored the mechanism of phytotoxicity of eugenol, a monoterpenoid alcohol,
      proposed as a natural herbicide. Eugenol (100-1000 uM) retarded the germination
      of Avena fatua and strongly inhibited its root growth compared to the coleoptile
      growth. We further investigated the underlying physiological and biochemical
      alterations leading to the root growth inhibition. Eugenol induced the generation
      of reactive oxygen species (ROS) leading to oxidative stress and membrane damage
      in the root tissue. ROS generation measured in terms of hydrogen peroxide,
      superoxide anion and hydroxyl radical content increased significantly in the
      range of 24 to 144, 21 to 91, 46 to 173% over the control at 100 to 1000 uM
      eugenol, respectively. The disruption in membrane integrity was indicated by 25
      to 125% increase in malondialdehyde (lipid peroxidation byproduct), and decreased
      conjugated diene content (~10 to 41%). The electrolyte leakage suggesting
      membrane damage increased both under light as well as dark conditions measured
      over a period from 0 to 30 h. In defense to the oxidative damage due to eugenol,
      a significant upregulation in the ROS-scavenging antioxidant enzyme machinery was
      observed. The activities of superoxide dismutases, catalases, ascorbate
      peroxidases, guaiacol peroxidases and glutathione reductases were elevated by
      ~1.5 to 2.8, 2 to 4.3, 1.9 to 5.0, 1.4 to 3.9, 2.5 to 5.5 times, respectively, in
      response to 100 to 1000 uM eugenol. The study concludes that eugenol inhibits
      early root growth through ROS-mediated oxidative damage, despite an activation of
      the antioxidant enzyme machinery.

PMID- 25752433
TI  - Co-silence of the coatomer beta and v-ATPase A genes by siRNA feeding reduces
      larval survival rate and weight gain of cotton bollworm, Helicoverpa armigera.
AB  - Coatomer and v-ATPase are two genes expressed in insect midgut epithelial cells
      and their knockdown is lethal to insect larvae. To investigate the RNAi response
      mediated by multiple siRNA duplexes, partial length cDNA of Helicoverpa armigera
      coatomer beta and v-ATPase A was cloned and siRNA feeding-based RNAi was
      performed. Simultaneous ingestion of siRNAs specific to the H. armigera coatomer
      beta and v-ATPase A led to co-silencing of the target genes and reduction in
      larval survival rate and weight gain. These results suggest that silencing two
      genes by feeding of multiple siRNAs is a good RNAi strategy. 

PMID- 25752434
TI  - Elevated expression of esterase and cytochrome P450 are related with lambda
      cyhalothrin resistance and lead to cross resistance in Aphis glycines Matsumura.
AB  - A resistant strain of the Aphis glycines Matsumura (CRR) has developed 76.67-fold
      resistance to lambda-cyhalothrin compared with the susceptible (CSS) strain.
      Synergists piperonyl butoxide (PBO), S,S,S-Tributyltrithiophosphate (DEF) and
      triphenyl phosphate (TPP) dramatically increased the toxicity of lambda
      cyhalothrin to the resistant strain. Bioassay results indicated that the CRR
      strain had developed high levels of cross-resistance to chlorpyrifos (11.66
      fold), acephate (8.20-fold), cypermethrin (53.24-fold), esfenvalerate (13.83
      fold), cyfluthrin (9.64-fold), carbofuran (14.60-fold), methomyl (9.32-fold) and
      bifenthrin (4.81-fold), but did not have cross-resistance to chlorfenapyr,
      imidacloprid, diafenthiuron, abamectin. The transcriptional levels of CYP6A2
      like, CYP6A14-like and cytochrome b-c1 complex subunit 9-like increased
      significantly in the resistant strain than that in the susceptible. Similar trend
      were observed in the transcripts and DNA copy number of CarE and E4 esterase.
      Overall, these results demonstrate that increased esterase hydrolysis activity,
      combined with elevated cytochrome P450 monooxygenase detoxicatication, plays an
      important role in the high levels of lambda-cyhalothrin resistance and can cause
      cross-resistance to other insecticides in the CRR strain.

PMID- 25752435
TI  - Thiram activates NF-kappaB and enhances ICAM-1 expression in human microvascular
      endothelial HMEC-1 cells.
AB  - Thiram (TMTD) is a fungicidal and bactericidal agent used as antiseptic, seed
      disinfectant and animal repellent. In the light of known properties, thiram is
      considered to be used as an inhibitor of angiogenesis and/or inflammation. Since
      angiogenesis requires the growth of vascular endothelial cells we have used
      microvascular endothelial cell line HMEC-1 to elucidate the effect of thiram on
      normal and stimulated cells. We cultured HMEC-1 cells in the presence of thiram
      at low concentration (0.5 ug/mL or 2 ug/mL) (0.2 uM or 0.8 uM) or TNF-alpha (10
      ng/mL) alone, and thiram together with TNF-alpha. TNF-alpha was used as a
      cytokine that triggers changes characteristic for inflammatory state of the cell.
      We carried out an in vitro study aimed at assessing generation of reactive oxygen
      species (ROS), activation of NF-kappaB, and expression of cell adhesion molecules
      ICAM-1, VCAM-1, PECAM-1. It was found that TMTD produced ROS and activated NF
      kappaB. Activation of NF-kappaB was concurrent with an increase in ICAM-1
      expression on the surface of HMEC-1 cells. ICAM-1 reflects intensity of
      inflammation in endothelial cell milieu. The expression of VCAM-1 and PECAM-1 on
      these cells was not changed by thiram. It was also found that stimulation of the
      HMEC-1 cells with the pro-inflammatory cytokine TNF-alpha caused activation of
      ICAM-1 and VCAM-1 expression with concomitant decrease of PECAM-1 cell surface
      expression above the control levels. Treatment with thiram and TNF-alpha changed
      cellular response compared with effects observed after treatment with TNF-alpha
      alone, i.e. further increase of ICAM-1 expression and impairment of the TNF-alpha
      effect on PECAM-1 and VCAM-1 expression. This study demonstrated that thiram acts
      as a pro-oxidant, and elicits in endothelial cell environment effects
      characteristic for inflammation. However, when it is present concurrently with
      pro-inflammatory cytokine TNF-alpha interferes with its action.

PMID- 25752436
TI  - Atrazine induces apoptosis of SH-SY5Y human neuroblastoma cells via the
      regulation of Bax/Bcl-2 ratio and caspase-3-dependent pathway.
AB  - Atrazine (ATZ) is a well known herbicide that is frequently detected in ground
      and surface water at significant levels. Our objective was to study the toxic
      effect of ATZ on the human neuroblastoma (SH-SY5Y) cells, and the degree of
      cytotoxicity and morphological changes were followed during the cell death.
      Application of cytotoxicity bioassays indicates that ATZ (5-50 ug/mL) decreases
      cell viability in a dose- and time-dependent manner. The evidence of apoptosis
      was confirmed by an increase in caspase-3 activity, and cell death was blocked
      when caspase-3 activity was inhibited. Typical apoptotic phenotype that includes
      nuclear fragmentation, micro nuclei formation, DNA fragmentation and increase in
      the expressions apoptosis-associated markers Bax, p53 and p21 and decreased
      expression of Bcl-2 were observed in treated cells. We also observed dose
      dependent increase in reactive oxygen species (ROS) levels in ATZ-treated cells.
      These results suggest that ATZ-induces apoptosis and ROS levels in SH-SY5Y cells,
      and could be implicated in human neurodegenerative disorder. 

PMID- 25752438
TI  - A phase 2 randomized, double-blind, placebo-controlled study of the effect of VIA
      2291, a 5-lipoxygenase inhibitor, on vascular inflammation in patients after an
      acute coronary syndrome.
AB  - OBJECTIVE: Arachidonate 5-lipoxygenase (5-LO) is a key enzyme in the synthesis of
      leukotrienes. VIA-2291 is a potent 5-LO inhibitor, which has been shown to reduce
      hsCRP and noncalcified coronary plaque volume following an acute coronary
      syndrome (ACS). We aim to evaluate the effect of VIA-2291 on vascular
      inflammation compared to placebo using FDG-PET. METHODS: A Phase II, randomized,
      double-blind, parallel-group study was conducted in 52 patients with recent ACS
      assigned 1:1 to either 100 mg VIA-2291 or placebo for 24 weeks. The primary
      outcome was the effect of VIA-2291 relative to placebo on arterial inflammation
      detected by (18)fluorodeoxyglucose positron emission tomography (FDG-PET) within
      the index vessel after 24 weeks of daily treatment, compared to baseline.
      RESULTS: VIA-2291 was relatively well tolerated and was associated with a
      significant inhibition of the potent chemo-attractant LTB4, with a mean
      inhibition of activity of 92.8% (p<0.0001) at 6 weeks in the VIA-2291 group,
      without further significant change in inhibition at 24 weeks. However, for VIA
      2291 was not associated with significant difference in inflammation (target-to
      background ratio) compared to placebo at 24 weeks or 6 weeks of treatment.
      Further, VIA-2291 was not associated with a significant reduction in hsCRP from
      baseline after either 6 or 24 weeks of treatment. CONCLUSIONS: VIA-2291 is well
      tolerated and effectively reduces leukotriene production. However, inhibition of
      5-LO with VIA-2291 is not associated with significant reductions in vascular
      inflammation (by FDG-PET) or in blood inflammatory markers. Accordingly, this
      study does not provide evidence to support a significant anti-inflammatory effect
      of VIA-2291 in patients with recent ACS.

PMID- 25752437
TI  - Stem cell treatment of degenerative eye disease.
AB  - Stem cell therapies are being explored extensively as treatments for degenerative
      eye disease, either for replacing lost neurons, restoring neural circuits or,
      based on more recent evidence, as paracrine-mediated therapies in which stem cell
      derived trophic factors protect compromised endogenous retinal neurons from death
      and induce the growth of new connections. Retinal progenitor phenotypes induced
      from embryonic stem cells/induced pluripotent stem cells (ESCs/iPSCs) and
      endogenous retinal stem cells may replace lost photoreceptors and retinal pigment
      epithelial (RPE) cells and restore vision in the diseased eye, whereas treatment
      of injured retinal ganglion cells (RGCs) has so far been reliant on mesenchymal
      stem cells (MSC). Here, we review the properties of non-retinal-derived adult
      stem cells, in particular neural stem cells (NSCs), MSC derived from bone marrow
      (BMSC), adipose tissues (ADSC) and dental pulp (DPSC), together with ESC/iPSC and
      discuss and compare their potential advantages as therapies designed to provide
      trophic support, repair and replacement of retinal neurons, RPE and glia in
      degenerative retinal diseases. We conclude that ESCs/iPSCs have the potential to
      replace lost retinal cells, whereas MSC may be a useful source of paracrine
      factors that protect RGC and stimulate regeneration of their axons in the optic
      nerve in degenerate eye disease. NSC may have potential as both a source of
      replacement cells and also as mediators of paracrine treatment. 

PMID- 25752439
TI  - Involvement of fibrocytes in asthma and clinical implications.
AB  - Bloodborne fibrocytes are bone marrow-derived cells that participate in immune
      responses and exhibit pro-inflammatory and matrix remodelling properties. In
      patients with asthma receiving an adequate treatment, the blood fibrocyte count
      is very low and comparable to that obtained in healthy individuals. In these
      patients, a transient increase in fibrocyte numbers in the peripheral blood and
      in the airways occurs in concomitance with increased bronchial inflammation and
      reflects disease worsening and the need for more intensive treatment.
      Persistently elevated numbers of fibrocytes in the peripheral blood and in the
      bronchial mucosa are observed in chronically undertreated or corticosteroid
      resistant asthma and are associated with persistent airway inflammation and
      ongoing remodelling of the bronchial wall. The asthmatic bronchial epithelium is
      the main source of fibrocyte chemoattractants in asthma and contributes with T
      helper type 2 lymphocytes and eosinophils to promote the proliferation and pro
      remodelling function of recruited fibrocytes. The presence of elevated numbers of
      fibrocytes in the bronchial mucosa of allergic patients with undertreated or
      treatment-resistant asthma may also increase the risk of acute exacerbations
      because these cells can amplify T helper type 2 lymphocyte-driven inflammation on
      every exposure to the clinically relevant allergen and can promote further
      inflammation on rhinovirus infections by allowing viral replication and releasing
      additional pro-inflammatory factors. Improved methods for the isolation and
      functional analysis of pure populations of viable circulating fibrocytes have
      allowed a better understanding of the effector role of these cells. A reliable
      and clinically applicable assay has been developed to measure blood fibrocyte
      counts as outcome measure in future clinical trials. New therapeutic agents are
      needed to block both persistent inflammation and fibrocytosis in corticosteroid
      resistant asthma. 

PMID- 25752440
TI  - Algae after dark: mechanisms to cope with anoxic/hypoxic conditions.
AB  - Chlamydomonas reinhardtii is a unicellular, soil-dwelling (and aquatic) green
      alga that has significant metabolic flexibility for balancing redox equivalents
      and generating ATP when it experiences hypoxic/anoxic conditions. The diversity
      of pathways available to ferment sugars is often revealed in mutants in which the
      activities of specific branches of fermentative metabolism have been eliminated;
      compensatory pathways that have little activity in parental strains under
      standard laboratory fermentative conditions are often activated. The ways in
      which these pathways are regulated and integrated have not been extensively
      explored. In this review, we primarily discuss the intricacies of dark anoxic
      metabolism in Chlamydomonas, but also discuss aspects of dark oxic metabolism,
      the utilization of acetate, and the relatively uncharacterized but critical
      interactions that link chloroplastic and mitochondrial metabolic networks. 

PMID- 25752442
TI  - Effects of conducting media and gender on an electric pulp test.
AB  - AIMS: (1) To determine the pulpal sensory thresholds in human teeth obtained from
      using various EPT conducting media and (2) to determine whether there are gender
      differences. METHODOLOGY: One intact maxillary central incisor was randomly
      selected from each of 40 participants (20 male, 20 female) aged 19-24 year. A
      constant-current electrical stimulator (University of Bristol, UK) was used to
      apply electrical stimuli with different conducting media at intervals of 1 min on
      the middle of the crown to evaluate the sensory threshold of the tooth. The tip
      of the electrode was coated with a thin layer of test media. The sensory
      thresholds and the pain scores were measured simultaneously after applying
      stimuli twice a second and gradually increasing the intensity until felt by the
      participants. Test media included water-based gels (K-Y UltraGel; Xylocaine 2%
      Jelly, electrode gel, fluoride gel) and toothpastes (Colgate Total; Sensodyne
      Repair & Protect; Dentiste' Plus White; Sparkle White). The sensory threshold
      data were evaluated using two-way anova followed by the Tukey test. RESULTS:
      Xylocaine 2% Jelly and fluoride gel evoked significantly lower threshold values
      when compared with Sensodyne Repair & Protect (P < 0.001). With all test media,
      the mean sensory threshold from the female group was significantly lower than
      that of the male group (P < 0.001). CONCLUSION: The sensory thresholds to
      electrical stimuli in human teeth was influenced by the type of conducting media
      and gender.

PMID- 25752443
TI  - Neural processing of auditory signals in the time domain: delay-tuned coincidence
      detectors in the mustached bat.
AB  - The central auditory system produces combination-sensitive neurons tuned to a
      specific combination of multiple signal elements. Some of these neurons act as
      coincidence detectors with delay lines for the extraction of spectro-temporal
      information from sounds. "Delay-tuned" neurons of mustached bats are tuned to a
      combination of up to four signal elements with a specific delay between them and
      form a delay map. They are produced in the inferior colliculus by the coincidence
      of the rebound response following glycinergic inhibition to the first harmonic of
      a biosonar pulse with the short-latency response to the 2nd-4th harmonics of its
      echo. Compared with collicular delay-tuned neurons, thalamic and cortical ones
      respond more to pulse-echo pairs than individual sounds. Cortical delay-tuned
      neurons are clustered in the three separate areas. They interact with each other
      through a circuit mediating positive feedback and lateral inhibition for
      adjustment and improvement of the delay tuning of cortical and subcortical
      neurons. The current article reviews the mechanisms for delay tuning and the
      response properties of collicular, thalamic and cortical delay-tuned neurons in
      relation to hierarchical signal processing. 

PMID- 25752444
TI  - Development of genome-wide microsatellite genetic resources in a commercially
      important African freshwater fish species - the Nile perch, Lates niloticus.

PMID- 25752441
TI  - CD103+ Tumor Infiltrating Lymphocytes Predict a Favorable Prognosis in Urothelial
      Cell Carcinoma of the Bladder.
AB  - PURPOSE: CD8(+) TILs at different tumor sites have diverse clinical attributes,
      which might result from distinct tumor microenvironments that promote
      differentiation into distinct subsets. However, only a few markers have been
      identified that can define CD8(+) T-cell subsets. CD103 is a marker of tissue
      resident memory CD8(+) T cells. In this retrospective study we investigated the
      cellular source and clinical significance of CD103 expression in urothelial cell
      carcinoma of bladder tissues in situ. MATERIALS AND METHODS: Immunohistochemistry
      and immunofluorescence were used to identify the cellular source of CD103 in
      bladder urothelial cell carcinoma tissues. Kaplan-Meier analysis and Cox
      proportional hazards regression models were applied to estimate overall and
      recurrence-free survival in 302 patients with bladder urothelial cell carcinoma.
      RESULTS: CD8(+) T cells but not natural killer cells accounted for most CD103
      expressing cells in bladder urothelial cell carcinoma tissues. Notably CD103(+)
      cells were predominantly located in intratumor regions rather than in associated
      stroma (p < 0.0001). The density of intratumor CD103(+) TILs was inversely
      associated with tumor size (p < 0.0001) and could represent a favorable
      prognostic predictor of overall and recurrence-free survival (p = 0.002 and
      0.011, respectively). Moreover, intratumor CD103(+) TILs were positively
      associated with the expression of cognate ligand E-cadherin in intratumor regions
      of bladder urothelial cell carcinoma tissues (p = 0.008). CONCLUSIONS: Our
      findings suggest that CD8(+) T cells might have a significant role in tumor
      immunity by expressing CD103 in intratumor regions of bladder urothelial cell
      carcinoma tissues. Intratumor CD103(+) TILs could potentially serve as a
      prognostic marker in patients with bladder urothelial cell carcinoma.

PMID- 25752445
TI  - A single nucleotide deletion in exon 3 of the HLA-C*07:02:01:01 allele produces a
      novel HLA-C*07 null allele, HLA-C*07:393N.
AB  - A single nucleotide deletion in HLA-C*07:02:01:01 results in a novel null allele,
      HLA-C*07:393N. 

PMID- 25752447
TI  - Comment on Obsessive-compulsive behaviour related cutaneous ulcers: two cases
      with therapeutic considerations.

PMID- 25752446
TI  - The contribution of astrocytes and microglia to traumatic brain injury.
AB  - Traumatic brain injury (TBI) represents a major cause of death and disability in
      developed countries. Brain injuries are highly heterogeneous and can also trigger
      other neurological complications, including epilepsy, depression and dementia.
      The initial injury often leads to the development of secondary sequelae; cellular
      hyperexcitability, vasogenic and cytotoxic oedema, hypoxia-ischaemia, oxidative
      stress and inflammation, all of which influence expansion of the primary lesion.
      It is widely known that inflammatory events in the brain following TBI contribute
      to the widespread cell death and chronic tissue degeneration. Neuroinflammation
      is a multifaceted response involving a number of cell types, both within the CNS
      and in the peripheral circulation. Astrocytes and microglia, cells of the CNS,
      are considered key players in initiating an inflammatory response after injury.
      These cells are capable of secreting various cytokines, chemokines and growth
      factors, and following injury to the CNS, undergo changes in morphology.
      Ultimately, these changes can influence the local microenvironment and thus
      determine the extent of damage and subsequent repair. This review will focus on
      the roles of microglia and astrocytes following TBI, highlighting some of the key
      processes, pathways and mediators involved in this response. Additionally, both
      the beneficial and the detrimental aspects of these cellular responses will be
      examined using evidence from animal models and human post-mortem TBI studies.

PMID- 25752448
TI  - Responses in gut microbiota and fat metabolism to a halogenated methane analogue
      in Sprague Dawley rats.
AB  - Recent studies on germ-free mice show that intestinal methanogens may be closely
      associated with host's adipose metabolism. The present study aimed to investigate
      effects of inhibition of intestinal methanogen populations on host fat metabolism
      by establishing a healthy Sprague Dawley (SD) rat model through the intragastric
      administration of bromochlordomethane (BCM). Forty-five 8-week old healthy male
      SD rats were randomly divided into five groups including one control and four BCM
      treatments. The experiment lasted 60 days with two separate 30-day experimental
      periods. At the end of first period, three BCM treatment groups were further
      used: one group continued with BCM treatment, one group stopped with BCM
      treatment, and the other one inoculated with faecal mixture of methanogens from
      rats. Results showed that the methanogen population in feces was reduced sixfold
      with no effect on the bacterial community by daily dosing with BCM. Daily gain,
      epididymal fat pad weight, levels of plasma low-density lipoprotein and
      cholesterol were significantly higher in the BCM-treated animals, while the high
      density lipoprotein was lower than that of the control. The expression of
      PPARgamma, LPL, PP2A, SREBP-1c, ChREBP, FASN and adiponectin genes in BCM
      treatment group was universally upregulated, while the expression of Fiaf gene
      was downregulated. After termination of BCM treatment and followed either with or
      without re-inocubation with faecal methanogen mixture, the rats had their faecal
      methanogen populations, blood parameters and gene expression returned to the
      original level. Results suggest that regulation of gut methanogens might be a
      possible approach to control host body weight. 

PMID- 25752449
TI  - A systematic review of motivational interviewing for weight loss among adults in
      primary care.
AB  - Motivational interviewing (MI) is a client-centred method of intervention focused
      on enhancing intrinsic motivation and behaviour change. A previous review of the
      literature and meta-analyses support the effectiveness of MI for weight loss.
      None of these studies, however, focused on the bourgeoning literature examining
      MI for weight loss among adults within primary care settings, which confers
      unique barriers to providing weight loss treatment. Further, the current review
      includes 19 studies not included in previous reviews or meta-analyses. We
      conducted a comprehensive review of PubMed, MI review papers, and citations from
      relevant papers. A total of 24 adult randomized controlled trials were
      identified. MI interventions typically were provided individually by a range of
      clinicians and compared with usual care. Few studies provided adequate
      information regarding MI treatment fidelity. Nine studies (37.5%) reported
      significant weight loss at post-treatment assessment for the MI condition
      compared with control groups. Thirteen studies (54.2%) reported MI patients
      achieving at least 5% loss of initial body weight. There is potential for MI to
      help primary care patients lose weight. Conclusions, however, must be drawn
      cautiously as more than half of the reviewed studies showed no significant weight
      loss compared with usual care and few reported MI treatment fidelity. 

PMID- 25752450
TI  - Digging for gold nuggets: uncovering novel candidate genes for variation in
      gastrointestinal nematode burden in a wild bird species.
AB  - The extent to which genotypic variation at a priori identified candidate genes
      can explain variation in complex phenotypes is a major debate in evolutionary
      biology. Whereas some high-profile genes such as the MHC or MC1R clearly do
      account for variation in ecologically relevant characters, many complex
      phenotypes such as response to parasite infection may well be underpinned by a
      large number of genes, each of small and effectively undetectable effect. Here,
      we characterize a suite of novel candidate genes for variation in
      gastrointestinal nematode (Trichostrongylus tenuis) burden among red grouse
      (Lagopus lagopus scotica) individuals across a network of moors in north-east
      Scotland. We test for associations between parasite load and genotypic variation
      in twelve genes previously identified to be differentially expressed in
      experimentally infected red grouse or genetically differentiated among red grouse
      populations with overall different parasite loads. These genes are associated
      with a broad physiological response including immune system processes. Based on
      individual-level generalized linear models, genotypic variants in nine genes were
      significantly associated with parasite load, with effect sizes accounting for
      differences of 514-666 worms per bird. All but one of these variants were
      synonymous or untranslated, suggesting that these may be linked to protein-coding
      variants or affect regulatory processes. In contrast, population-level analyses
      revealed few and inconsistent associations with parasite load, and little
      evidence of signatures of natural selection. We discuss the broader significance
      of these contrasting results in the context of the utility of population genomics
      and landscape genomics approaches in detecting adaptive genomic signatures.

PMID- 25752451
TI  - The effects of activating prior topic and metacognitive knowledge on text
      comprehension scores.
AB  - BACKGROUND: Research on prior knowledge activation has consistently shown that
      activating learners' prior knowledge has beneficial effects on learning. If
      learners activate their prior knowledge, this activated knowledge serves as a
      framework for establishing relationships between the knowledge they already
      possess and new information provided to them. Thus far, prior knowledge
      activation has dealt primarily with topic knowledge in specific domains.
      Students, however, likely also possess at least some metacognitive knowledge
      useful in those domains, which, when activated, should aid in the deployment of
      helpful strategies during reading. AIMS: In this study, we investigated the
      effects of both prior topic knowledge activation (PTKA) and prior metacognitive
      knowledge activation (PMKA) on text comprehension scores. SAMPLES & METHODS:
      Eighty-eight students in primary education were randomly distributed amongst the
      conditions of the 2 * 2 (PTKA yes/no * PMKA yes/no) designed experiment. RESULTS:
      Results show that activating prior metacognitive knowledge had a beneficial
      effect on text comprehension, whereas activating prior topic knowledge, after
      correcting for the amount of prior knowledge, did not. CONCLUSIONS: Most studies
      deal with explicit instruction of metacognitive knowledge, but our results show
      that this may not be necessary, specifically in the case of students who already
      have some metacognitive knowledge. However, existing metacognitive knowledge
      needs to be activated in order for students to make better use of this knowledge.

PMID- 25752452
TI  - Successes and failures of compulsory risk mitigation: re-evaluating the Turkish
      Catastrophe Insurance Pool.
AB  - The Turkish Catastrophe Insurance Pool (TCIP) is one of the best practices of
      public-private partnerships in an emerging market designed to reduce economic
      losses from disasters. This paper reviews the application of this compulsory
      mechanism along with data relating to the performance of the scheme following
      recent earthquakes in Turkey. We also consider the current perceptions of Turkish
      society towards the TCIP and how they can be enhanced. Our conclusions aim to
      assist stakeholders in government, homeowners, insurance companies, media, banks
      and civil society to appreciate the value of the system and key actions necessary
      to improve it. 

PMID- 25752453
TI  - White matter integrity in young smokers: a tract-based spatial statistics study.
AB  - Previous diffusion tensor imaging (DTI) studies revealed contradictory effects of
      smoking on fractional anisotropy (FA). Multiple DTI-derived indices may help to
      deduce the pathophysiological type of white matter (WM) changes and provide more
      specific biomarkers of WM neuropathology in the whole brain of young smokers.
      Twenty-three young smokers and 22 age-, education- and gender-matched healthy non
      smoking controls participated in this study. Tract-based spatial statistics was
      employed to investigate the WM microstructure in young smokers by integrating
      multiple indices, including FA, mean diffusivity (MD), radial diffusivity (RD)
      and axial diffusivity (AD). Compared with healthy non-smoking controls, young
      smokers showed significantly increased FA with increased AD and decreased RD in
      several brain regions, while no difference in MD was observed. Specifically, the
      overlapped WM regions with increased FA, increased AD and decreased RD were found
      in the right posterior limb of the internal capsule, the right external capsule
      and the right superior corona radiata. Additionally, average FA and RD values in
      the WM regions mentioned earlier were significantly correlated with pack-years
      and Fagerstrom Test for Nicotine Dependence, while no correlation in AD was
      found. The WM tracts with increased FA may be more associated with RD, rather
      than AD in young smokers. We suggested that WM properties of several fibres in
      young smokers may be the biomarker as the cumulative effect and severity of
      nicotine dependence. 

PMID- 25752454
TI  - mTOR inhibition suppresses established epilepsy in a mouse model of cortical
      dysplasia.
AB  - OBJECTIVE: Hyperactivation of the mechanistic target of rapamycin (mTOR; also
      known as mammalian target of rapamycin) pathway has been demonstrated in human
      cortical dysplasia (CD) as well as in animal models of epilepsy. Although
      inhibition of mTOR signaling early in epileptogenesis suppressed epileptiform
      activity in the neuron subset-specific Pten knockout (NS-Pten KO) mouse model of
      CD, the effects of mTOR inhibition after epilepsy is fully established were not
      previously examined in this model. Here, we investigated whether mTOR inhibition
      suppresses epileptiform activity and other neuropathological correlates in adult
      NS-Pten KO mice with severe and well-established epilepsy. METHODS: The
      progression of epileptiform activity, mTOR pathway dysregulation, and associated
      neuropathology with age in NS-Pten KO mice were evaluated using video
      electroencephalography (EEG) recordings, Western blotting, and
      immunohistochemistry. A cohort of NS-Pten KO mice was treated with the mTOR
      inhibitor rapamycin (10 mg/kg i.p., 5 days/week) starting at postnatal week 9 and
      video-EEG monitored for epileptiform activity. Western blotting and
      immunohistochemistry were performed to evaluate the effects of rapamycin on the
      associated pathology. RESULTS: Epileptiform activity worsened with age in NS-Pten
      KO mice, with parallel increases in the extent of hippocampal mTOR complex 1 and
      2 (mTORC1 and mTORC2, respectively) dysregulation and progressive astrogliosis
      and microgliosis. Rapamycin treatment suppressed epileptiform activity, improved
      baseline EEG activity, and increased survival in severely epileptic NS-Pten KO
      mice. At the molecular level, rapamycin treatment was associated with a reduction
      in both mTORC1 and mTORC2 signaling and decreased astrogliosis and microgliosis.
      SIGNIFICANCE: These findings reveal a wide temporal window for successful
      therapeutic intervention with rapamycin in the NS-Pten KO mouse model, and they
      support mTOR inhibition as a candidate therapy for established, late-stage
      epilepsy associated with CD and genetic dysregulation of the mTOR pathway.

PMID- 25752455
TI  - Involvement of ATF3 in the negative regulation of iNOS expression and NO
      production in activated macrophages.
AB  - Macrophage-associated nitric oxide (NO) production plays a crucial role in the
      pathogenesis of tissue damage. However, negative factors that regulate NO
      production remains poorly understood despite its significance of NO homeostasis.
      Here, we show that activating transcription factor 3 (ATF3), a transcriptional
      regulator of cellular stress responses, was strongly induced in activated
      macrophages and its depletion resulted in pronounced enhancement of inducible
      nitric oxide synthase (iNOS) gene expression and subsequently the induction of
      high levels of NO production. In response to lipopolysaccharide (LPS) and IFN
      gamma, ATF3 inhibited transcriptional activity of NF-kappaB by interacting with
      the N-terminal (1-200 amino acids) of p65 and was bound to the NF-kappaB
      promoter, leading to suppression of iNOS gene expression. In addition, inhibitory
      effects of ATF3 on iNOS and NO secretion were suppressed by inhibitor of casein
      kinase II (CK2) activity or its knockdown. Moreover, the levels of ATF3 were
      highly elevated in established cecal ligation and puncture or LPS-injected mice,
      a model of endotoxemia. ATF3 is also elevated in peritoneal macrophages.
      Collectively, our findings suggest that ATF3 regulates NO homeostasis by
      associating with NF-kappaB component, leading to the repression of its
      transcriptional activity upon inflammatory signals and points to its potential
      relevance for the control of cell injuries mediated by NO during macrophage
      activation.

PMID- 25752456
TI  - Glycogen synthase kinase 3beta inhibition promotes human iTreg differentiation
      and suppressive function.
AB  - Induced regulatory T cells (iTregs) are essential to maintain immunological
      tolerance, immune homeostasis and prevention of autoimmunity. Some studies
      suggest that glycogen synthase kinase 3beta (GSK3beta) is involved in the mouse
      iTreg differentiation; however, whether GSK3beta inhibits or enhances iTreg
      differentiation is still a matter of controversy. To address this issue, we have
      utilized human naive CD4(+) T cells and investigated whether GSK3 activity
      changes during iTreg differentiation and whether altering GSK3 activity
      influences the development of iTregs and its suppressive function. As a
      constitutively activated kinase, during iTreg differentiation GSK3beta became
      quickly deactivated (phosphorylated at serine 9), which is dependent on MAPK
      pathway rather than PI3-kinase/Akt pathway. Our results indicated that inhibition
      of GSK3beta by specific inhibitors, SB216763 or TDZD-8, promoted the
      differentiation of iTreg and increased their suppressive activity. In contrast,
      overexpression of GSK3beta significantly inhibited iTreg differentiation.
      Furthermore, GSK3beta inhibition enhanced iTreg differentiation through the TGF
      beta/Smad3 pathway. Taken together, this study demonstrates that inhibition of
      GSK3beta enhances human iTreg differentiation and its suppressive activity, and
      provides a rationale to target GSK3beta as a novel immunotherapeutic strategy.

PMID- 25752457
TI  - A novel CD40LG deletion causes the hyper-IgM syndrome with normal CD40L
      expression in a 6-month-old child.
AB  - The X-linked hyper-IgM syndrome (XHIGM) is the most common form of HIGM. Patients
      are clinically diagnosed on the basis of recurrent sinopulmonary infections,
      accompanied with low levels of IgG and IgA, normal to elevated levels of IgM, and
      the presence of peripheral B cells. Here, we have reported a novel deletion of
      four nucleotides in CD40LG exon 3, c.375_378delCAAA, which led to a frameshift
      mutation with a premature stop codon, p.Asn101*126. The deletion resulted in a
      truncated protein, in which majority of the extracellular domain was lost.
      However, detection of surface CD40L was still possible as the intracellular,
      transmembrane, and part of the extracellular domains were not affected. This
      indicated that this mutation did not affect protein stability and that
      immunodetection of CD40L expression is not enough for the diagnosis of XHIGM. Our
      study strongly suggests that genetic diagnosis for XHIGM should always be
      performed when clinical data support this diagnosis and CD40L protein is present.

PMID- 25752458
TI  - Comment on: "impact and cost-effectiveness of a universal strategy to promote
      physical activity in primary care".

PMID- 25752459
TI  - Reply to comment on "impact and cost-effectiveness of a universal strategy to
      promote physical activity in primary care".

PMID- 25752460
TI  - Genotypic characteristics of multidrug-resistant Pseudomonas aeruginosa from
      hospital wastewater treatment plant in Rio de Janeiro, Brazil.
AB  - AIMS: To investigate Pseudomonas aeruginosa isolates from a hospital wastewater
      treatment plant (HWTP), focusing on enzyme-based mechanisms of beta-lactams
      resistance and the genetic relatedness among isolates. METHODS AND RESULTS: Forty
      one Ps. aeruginosa strains recovered from a HWTP were identified by amplification
      of 16S rRNA gene. beta-lactamase production was screened by disc diffusion,
      CHROMagar extended-spectrum beta-lactamase (ESBL) and beta-lactamase strips. beta
      lactamase and ESBL producing isolates were investigated by PCR for the presence
      of ESBL, metallo-beta-lactamase and Klebsiella pneumoniae carbapenemase encoding
      genes. Thirty-four isolates (83%) were resistant to at least one antibiotic
      belonging to three or more classes. Out of these 34 isolates, 28 (82%) were
      classified as multidrug-resistant (MDR) and 6 (18%) extensively drug-resistant
      (XDR). Genetic relatedness by Enterobacterial Repetitive Intergenic Consensus
      sequence-PCR and Multilocus sequence typing analysis showed 20 distinct profiles
      and 15 sequencing types respectively. Clonal Complex 244 (CC244) shows the
      pathogenic potential of this clone carrying MDR and XDR strains from clinical,
      environmental and hospital waste sources. CONCLUSIONS: Our results suggest that
      treatment facilities for hospital wastewater can stimulate the increase of
      antimicrobial resistance bacteria and genes. SIGNIFICANCE AND IMPACT OF THE
      STUDY: The great genetic diversity of Ps. aeruginosa recovered from HWTP
      constantly released into aquatic systems allow the spread of antimicrobial
      resistant organisms and genes.

PMID- 25752461
TI  - The association of the QT interval with atrial fibrillation and stroke: the Multi
      Ethnic Study of Atherosclerosis.
AB  - BACKGROUND: Prolongation of the QT interval is associated with an increased risk
      of atrial fibrillation (AF) and stroke. OBJECTIVES: The purpose of this analysis
      was to determine if AF explains the association between prolonged QT and stroke.
      METHODS: A total of 6305 participants (mean age 62 +/- 10 years; 54% women; 38%
      whites; 27% blacks; 23% Hispanics; 12% Chinese-Americans) from the Multi-Ethnic
      Study of Atherosclerosis (MESA) were included in this analysis. A linear scale
      was used to compute heart rate-adjusted QT (QT(a)). Prolonged QT(a) was defined
      as >= 460 ms in women and >= 450 ms in men. Incident AF cases were identified
      using hospital discharge records and Medicare claims data. Vascular neurologists
      adjudicated stroke events by medical record review. Cox regression was used to
      examine the association between prolonged QT(a) and stroke with and without AF.
      RESULTS: A total of 216 (3.4%) of study participants had prolonged QT(a). Over a
      median follow-up of 8.5 years, 280 (4.4%) participants developed AF and 128
      (2.0%) participants developed stroke. In a multivariable Cox regression analysis
      adjusted for socio-demographics, cardiovascular risk factors, and potential
      confounders, prolonged QT(a) was associated with an increased risk of AF (HR =
      1.7, 95% CI 1.1, 2.6) and stroke (HR = 2.3, 95% CI 1.3, 4.1). When AF was
      included as a time-dependent covariate, the association between prolonged QT(a)
      and stroke was not substantively altered (HR = 2.4, 95% CI 1.3, 4.3). CONCLUSION:
      The increased risk of stroke in those with prolonged QT potentially is not
      explained by documented AF. Further research is needed to determine if
      subclinical AF explains the association between the QT interval and stroke.

PMID- 25752462
TI  - Low serum vitamin D levels are not associated with increased postoperative pain
      and opioid requirements: a historical cohort study.
AB  - PURPOSE: Vitamin D deficiency has been associated with chronic non-specific
      musculoskeletal pain syndromes; however, studies are lacking with respect to its
      relationship with postoperative pain. We tested the hypothesis that a lower
      preoperative vitamin D level is associated with increased postoperative pain
      and/or opioid consumption in morbidly obese patients who had laparoscopic
      bariatric surgery. METHODS: Data from 185 patients who underwent laparoscopic
      bariatric surgery at the Cleveland Clinic from 2005-2009 and had a vitamin D
      level checked within three months of their surgery were included in the analysis.
      We assessed the relationship between vitamin D levels and the time-weighted
      average (TWA) of pain scores and total opioid consumption using multivariable
      regression models adjusted for potential confounders. As a secondary analysis, we
      compared the TWA of pain scores and opioid consumption between patients who were
      vitamin D deficient (<= 20 ng.mL(-1)) and those who were not (vitamin D > 20
      ng.mL(-1)). RESULTS: The mean (SD) TWA pain score was 3.8 (1.5) and the median
      interquartile range [IQR] total opioid consumption (morphine equivalent) was 15.6
      [18.2] mg during the first 72 hr postoperatively. The median [IQR] vitamin D
      concentration was 21.8 [17.1] ng.mL(-1). The vitamin D level was not
      significantly associated with either the TWA pain score (Pearson correlation: 
      0.003; 97.5% confidence interval [CI]: -0.17 to 0.16) or opioid consumption
      (Spearman correlation: -0.13; 97.5% CI: -0.30 to 0.03). After adjusting for
      confounders, the estimated average change in TWA pain score was 0.01 (97.5% CI: 
      0.08 to 0.11) for a five-unit increase in vitamin D (P = 0.77). The estimated
      ratio of geometric means of total opioid consumption was 0.94 (97.5% CI: 0.86 to
      1.03) for a five-unit increase in vitamin D concentration (P = 0.12). No
      difference was found between patients with vitamin D concentrations > 20 ng.mL(
      1) and <= 20 ng.mL(-1) in either TWA pain score (P = 0.91) or total opioid
      consumption (P = 0.18). CONCLUSION: We did not find any association between
      preoperative vitamin D levels and postoperative pain scores/opioid consumption in
      morbidly obese patients undergoing bariatric surgery.

PMID- 25752463
TI  - Does the method of anesthesia really affect outcomes and survival after total
      joint replacement?

PMID- 25752464
TI  - Achromatopsia in three sibling Labrador Retrievers in the UK.
AB  - Achromatopsia was identified in three Labrador Retriever littermates. The dogs
      demonstrated day blindness, negotiating obstacles under low-light conditions, but
      apparently blind when outdoors. One of the dogs presented with immature bilateral
      diffuse posterior cortical cataracts and clinical signs of day blindness became
      apparent following cataract extraction surgery. Electroretinography demonstrated
      an absence of a cone photoreceptor response to a bright stimulus and a flicker
      response of 30 Hz in all three dogs. No fundic lesions have been apparent
      ophthalmoscopically in any of the dogs as the initial presentation of each case.
      No abnormalities were detected with DNA screening for known mutations of the
      CNGB3 gene in any of the dogs. 

PMID- 25752465
TI  - Decreased expression and activation of Stat3 in severe preeclampsia.
AB  - Severe preeclampsia (PE) is a major cause of maternal mortality and morbidity
      worldwide. Signal transducer and activator of transcription 3 (Stat3) signal
      pathway can modulate various fundamental cellular processes. However, whether
      Stat3 plays a role in the pathogenesis of severe PE is unknown. Therefore, in
      this study, the expression levels of Stat3 pathway-related genes and proteins,
      Stat3, pStat3, IL-6, Mcl-1L, Bcl-xL, survivin, MMP-2, and MMP-9, were evaluated
      by immunohistochemistry (IHC), Western blot analysis and real-time PCR in the
      severe preeclamptic placentas. Our results showed that Stat3 and pStat3
      immunoreactivity were localized in both extravillous cytotrophoblast cells and
      villous trophoblast cells in the placentas. As compared with normotensive
      pregnancies, significantly decreased expressions of Stat3 and pStat3 proteins
      were observed in extravillous cytotrophoblast cells, villous trophoblast cells
      and entire placentas in patients with severe PE. The expression levels of Stat3,
      IL-6, survivin and MMP-2 mRNA were significantly decreased in severe preeclamptic
      placentas, while Mcl-1L, Bcl-xL and MMP-9 mRNA levels were unchanged. IHC results
      further confirmed that there was a significant decrease of IL-6, survivin and MMP
      2 proteins expression in the severe preeclamptic placentas compared with the
      normal specimens. These findings suggested that decreased expression and
      activation of the Stat3 may be caused by decreased expression of a Stat3 upstream
      gene, such as IL-6. Decreased Stat3 expression and activation may play an
      important role in the pathogenesis of PE through regulation of the transcription
      of the Stat3 targeted genes survivin and MMP-2 to modulate apoptosis and invasion
      of placental trophoblastic cells. 

PMID- 25752466
TI  - Does childbirth play a role in the etiology of rectocele?
AB  - INTRODUCTION AND HYPOTHESIS: Rectoceles are common among parous women and they
      are believed to be due to disruption or distension of the rectovaginal septum as
      a result of childbirth. However, the etiology of rectocele is likely to be more
      complex since posterior compartment prolapse does occur in nulliparous women.
      This study was designed to determine the role of childbearing as an etiological
      factor in true radiological rectocele. METHODS: This was a secondary analysis of
      the data from 657 primiparous women recruited as part of a previously reported
      study and another ongoing prospective study. Women were invited for antenatal and
      postnatal appointments comprising an interview, clinical examination and
      translabial ultrasonography. The presence and depth of any rectocele were
      determined on maximum Valsalva maneuver, as was descent of the rectal ampulla.
      Potential demographic and obstetric factors as predictors of rectocele
      development were evaluated using either multiple regression or logistic
      regression analysis as appropriate. RESULTS: A true rectocele was identified in
      4% of women antenatally and in 16% after childbirth (P < 0.001). Mean rectocele
      depth was 13.5 mm (10 - 23.2 mm). The mean antepartum position of the rectal
      ampulla on Valsalva maneuver was 4.39 mm above and it was 1.64 mm below the
      symphysis pubis postpartum (P < 0.0001). De novo appearance of true rectocele was
      significantly associated with a history of previous <20 weeks pregnancy and fetal
      birth weight. Body mass index and length of the second stage were associated with
      rectocele depth increase. CONCLUSIONS: Childbirth seems to play a distinct role
      in the pathogenesis of rectocele. Both maternal and fetal factors seem to
      contribute.

PMID- 25752467
TI  - Results of primary versus recurrent surgery to treat stress urinary incontinence
      in women.
AB  - INTRODUCTION AND HYPOTHESIS: We compared cure rates and complication rates in
      patients who had undergone primary or recurrent (secondary) surgery for stress
      urinary incontinence (SUI). METHODS: A retrospective cohort study that included
      patients who underwent surgery to treat SUI in a tertiary referral center was
      carried out. All patients had, predominantly, SUI. Exclusion criteria were
      patients with a neurogenic bladder or a neobladder and patients without
      postoperative follow-up (FU). The primary objective was to assess the success
      rate, defined as cured SUI or improved SUI at six weeks and at the latest
      available moment of FU. The secondary objective was to assess complications.
      RESULTS: A total of 541 women with SUI underwent surgery for SUI between 2002 and
      2010. After exclusion of 102 patients a total of 242 patients with primary SUI
      and 197 patients with recurrent SUI were identified. The success rate at first FU
      was 89 %. At last FU (median 205 days) the success rate was 83 % (P < 0.01).
      There were no significant differences in success rate between primary and
      recurrent surgery at first FU. The overall success rate of primary surgery was 86
      %; for recurrent surgery it was 79 %. During surgery, 27 bladder injuries
      occurred (6.2 %), with no significant difference between the two groups. At last
      FU, 11 patients (2.6 %) had persistent residual volume, necessitating prolonged
      clean intermittent self-catheterization. CONCLUSIONS: The results of recurrent
      surgery to treat recurrent or persistent SUI are still good in experienced hands
      and do not significantly differ from results of primary surgery. The complication
      rates are comparable to those of primary surgery.

PMID- 25752468
TI  - Collagenoma and voiding dysfunction as complications of periurethral bulking.
AB  - Peri-urethral bulking agents are used as a management option for selected
      patients with stress urinary incontinence (SUI). We present a case of urinary
      retention and a large firm para-urethral vaginal mass as a complication of peri
      urethral collagen injections 3 years before presentation. The patient was managed
      successfully with complete surgical resection of the mass. Subsequent recurrent
      SUI was managed using a rectus fascial sling. 

PMID- 25752469
TI  - Urinary retention and uterine leiomyomas: a case series and systematic review of
      the literature.
AB  - Uterine leiomyomas are underrecognized as a cause of acute urinary retention
      (AUR) in women. The objective of this study was to present a case series and
      systematic review of the literature, to elucidate the pathogenesis of leiomyoma
      related AUR, and to suggest management strategies. We included patients
      presenting with AUR and uterine leiomyomas at our institution between January
      2011 and December 2013. Further, we systematically searched the Cochrane Library
      (from 1898 to June 2014), EMBASE (from 1947 to June 2014), and MEDLINE (from 1946
      to June 2014) databases according to the PRISMA guidelines. A total of six
      patients with AUR and leiomyomas presented to our institution. Through the
      systematic review, another 31 cases of AUR were identified. Combined patient ages
      ranged from 25 to 75 years. Uterine size ranged from 10 to 22 weeks on physical
      examination and from 5.5 to 26 cm on imaging. The dominant leiomyoma size ranged
      from 5.7 to 22.4 cm. Significant risk factors were posterior or fundal leiomyoma
      position and the presence of a retroverted uterus. Proposed mechanisms for
      leiomyoma-related AUR include proximal urethra or bladder-neck compression,
      premenstrual pelvic congestion, vascular steal effect, and compression of
      pudendal or sacral nerves. Patients were treated with hysterectomy, myomectomy,
      uterine fibroid embolization, hormones, or by conservative management alone. In
      the absence of neurologic disorders or other risk factors, neither urodynamic
      studies nor neuromuscular testing seem to contribute to diagnosis or guide
      management in women with uterine leiomyomas and AUR. Patients presenting to
      gynecologists seem to experience shorter times to diagnosis and treatment
      compared with other specialties. It is essential to recognize leiomyomas as a
      potential cause of AUR in order to reduce unnecessary testing and delays in
      diagnosis and management.

PMID- 25752470
TI  - A monoclonal antibody with anti-D-like activity in murine immune thrombocytopenia
      requires Fc domain function for immune thrombocytopenia ameliorative effects.
AB  - BACKGROUND: The mechanism of action of anti-D in ameliorating immune
      thrombocytopenia (ITP) remains unclear. The monoclonal antibody (MoAb) Ter119,
      which targets murine red blood cells (RBCs), has been shown to mimic the effect
      of anti-D in improving antibody-mediated murine ITP. The mechanism of Ter119
      mediated ITP amelioration, especially the role of the antigen-binding and Fc
      domains, remains untested. A functional Fc domain is crucial for many therapeutic
      MoAb activity; therefore, the requirement of Ter119 Fc domain in ITP amelioration
      is investigated using outbred CD-1 mice. STUDY DESIGN AND METHODS: Ter119
      variants, including Ter119 F(ab')2 fragments, deglycosylated Ter119, and
      afucosylated Ter119, were generated to test their effect in ameliorating antibody
      induced murine ITP. In vivo inhibition of FcgammaRIII and FcgammaRIIB was
      achieved using the Fab fragment of the FcgammaRIII/FcgammaRIIB-specific MoAb
      2.4G2. RESULTS: Ter119 F(ab')2 fragments and deglycosylated Ter119 were unable to
      ameliorate murine ITP or mediate phagocytosis of RBCs by RAW264.7 macrophages in
      vitro. Inhibition of FcgammaRIII and FcgammaRIIB, as well as Ter119
      defucosylation, do not affect Ter119-mediated ITP amelioration. CONCLUSION: The
      Fc domain of Ter119, as well as its Fc glycosylation, is required for Ter119
      mediated ITP amelioration. Moreover, both Fc and Fc glycosylation are required
      for Ter119-mediated phagocytosis in vitro. These findings demonstrate the
      importance of the Fc domain in a therapeutic MoAb with anti-D-like activity.

PMID- 25752471
TI  - Reading the signs: Microrips as a prognostic sign for impending RPE tear
      development.

PMID- 25752472
TI  - Myocardial insult and arrhythmias after acute hemorrhage in horses.
AB  - OBJECTIVE: The objectives of this investigation were to: (1) Determine if acute
      hemorrhage is associated with increased plasma cardiac troponin I (cTnI)
      concentration or cardiac arrhythmias, (2) to describe the types of arrhythmias
      and their clinical course in horses following acute hemorrhage, (3) to determine
      the ability of clinical or clinicopathological variables to predict an increase
      in cTnI concentration and the presence of arrhythmias, and (4) to determine the
      associations of cTnI and cardiac arrhythmias with outcome. DESIGN: Prospective
      observational study. SETTING: Large animal veterinary teaching hospital. ANIMALS:
      Eleven client-owned adult horses admitted for treatment of acute hemorrhage (HG)
      and 4 adult horses undergoing controlled blood collection (BDG). METHODS: Serial
      cTnI concentrations were measured and continuous ECGs were obtained from the HG
      and BDG groups. Statistical tests were used to determine associations among acute
      hemorrhage and plasma cTnI concentrations, the presence of cardiac arrhythmias,
      clinicopathologic data (heart rate [HR], packed cell volume [PCV], total plasma
      protein [TPP], plasma lactate, and plasma creatinine concentrations), and
      outcome. RESULTS: Plasma cTnI concentration and ECG were within reference
      intervals at all time points in the BDG. All horses in the HG had increased cTnI
      (ranging from 0.1-29.9 ng/mL). Arrhythmias were detected in 8 of these horses.
      There was an association between acute hemorrhage and increased cTnI (P = 0.004,
      rho = 0.77), and the presence of arrhythmias (P = 0.026, rho = 0.64). There were
      associations among plasma cTnI concentration and the presence of arrhythmias (P =
      0.005), arrhythmias requiring treatment (P = 0.036), and poor outcome (P =
      0.024). CONCLUSIONS: Acute hemorrhage results in myocardial injury that can be
      detected by measuring cTnI concentration. Arrhythmias were frequent in
      hospitalized horses following acute hemorrhage.

PMID- 25752473
TI  - Using Medical Claims for Policy Effectiveness Surveillance: Reimbursement and
      Utilization of Abdomen/Pelvis Computed Tomography Scans.
AB  - OBJECTIVE: To quantify changes in private insurance payments for and utilization
      of abdominal/pelvic computed tomography scans (CTs) after 2011 changes in CPT
      coding and Medicare reimbursement rates, which were designed to reduce costs
      stemming from misvalued procedures. DATA SOURCES: TruvenHealth Analytics
      MarketScan Commercial Claims and Encounters database. STUDY DESIGN: We used
      difference-in-differences models to compare combined CTs of the abdomen/pelvis to
      CTs of the abdomen or pelvis only. Our main outcomes were inflation-adjusted log
      payments per procedure, daily utilization rates, and total annual payments. DATA
      EXTRACTION METHODS: Claims data were extracted for all abdominal/pelvic CTs
      performed in 2009-2011 within noncapitated, employer-sponsored private plans.
      PRINCIPAL FINDINGS: Adjusted payments per combined CTs of the abdomen/pelvis
      dropped by 23.8 percent (p < .0001), and their adjusted daily utilization rate
      accelerated by 0.36 percent (p = .034) per month after January 2011. Utilization
      rate of abdominal-only or pelvic-only CTs dropped by 5.0 percent (p < .0001).
      Total annual payments for combined CTs of the abdomen/pelvis decreased in 2011
      despite the increased utilization. CONCLUSIONS: Private insurance payments for
      combined CTs of the abdomen/pelvis declined and utilization accelerated
      significantly after 2011 policy changes. While growth in total annual payments
      was contained in 2011, it may not be sustained if 2011 utilization trends
      persist.

PMID- 25752474
TI  - Squamoid eccrine ductal carcinoma of the scalp.
AB  - An 85-year-old man presented with an ulcerated pruritic nodule on the scalp.
      Histology of a deep curette specimen showed the typical features of a squamoid
      eccrine ductal carcinoma: superficial squamous differentiation and deep ductal
      structures. 

PMID- 25752475
TI  - Effect of chronic corticosterone application on depression-like behavior in
      C57BL/6N and C57BL/6J mice.
AB  - Many studies using genetic mouse models are performed with animals on either one
      of the two closely related genetic backgrounds, C57BL/6J or C57BL/6N. These
      strains differ only in a few genetic loci, but have some phenotypic differences
      that also affect behavior. In order to determine the effects of chronic stress
      hormone exposure, which is relevant for the pathogenesis of psychiatric
      disorders, we investigated here the behavioral manifestations of long-term
      increase in corticosterone levels. Thus, male mice from both sub-strains were
      subcutaneously implanted with corticosterone (20 mg) or placebo pellets that
      released the hormone for a period of 21 days and resulted in significantly
      elevated plasma corticosterone levels. Corticosterone significantly increased
      food intake in B6N, but not in B6J mice. At various time points after pellet
      implantation, we performed tests relevant to activity and emotional behaviors.
      B6J mice displayed a generally higher activity in the home cage and the open
      field. Corticosterone decreased the activity. In B6N mice, corticosterone also
      decreased sucrose preference, worsened the coat state and increased forced swim
      immobility, while it had no effect in the B6J strain. Altogether, these results
      indicate that B6N mice are more sensitive to some of the effects of chronic
      corticosterone treatment than B6J mice. 

PMID- 25752476
TI  - Transcatheter aortic valve replacement: focus on sex-related differences in
      outcomes.
AB  - Transcatheter aortic valve replacement (TAVR) has transformed the management of
      severe aortic stenosis for high-risk and inoperable patients. The 10-year
      experience in Europe has proven the technology to be safe and effective in select
      populations. The PARTNER trial, the first prospective, randomized, controlled
      trial for TAVR, showed the technology to be superior to medical management for
      inoperable patients and equivalent to surgical aortic valve replacement for high
      risk patients. Research in cardiovascular medicine has been dominated by studies
      on the male sex, due to the incidence of the disease process and partly due to
      historic predominance of male subjects in research studies. Alternatively, TAVR
      studies focused on high-risk and inoperable patients who are equally distributed
      by sex. Although sex-related differences are apparent in their baseline
      characteristics, outcomes have been mixed, with evidence suggesting that female
      patients may have a mortality advantage with TAVR. Herein we review the TAVR
      procedure and devices currently available and focus our discussion on outcomes
      after transcatheter or surgical aortic valve replacement in patients with severe
      aortic stenosis. 

PMID- 25752477
TI  - Are older women more likely to receive surgical treatment for stress urinary
      incontinence since the introduction of the mid-urethral sling? An examination of
      Hospital Episode Statistics data.
AB  - OBJECTIVE: To examine the trends in surgical treatment of stress urinary
      incontinence (SUI) in older women since the introduction of the mid-urethral
      sling. DESIGN: Analysis of data from Hospital Episode Statistics (HES) between
      2000 and 2012. SETTING AND POPULATION: All surgical procedures for SUI in the
      National Health Service (NHS) in England. METHODS: Retrospective cohort analysis
      of Hospital Episode Statistics for England from 2000 to 2012. MAIN OUTCOME
      MEASURES: Number of invasive, less invasive, and urethral bulking procedures
      performed in women in three age groups. RESULTS: There was a 90% fall in the
      number of invasive surgical treatments for SUI and a four-fold increase in the
      number of mid-urethral slings over this time. The total number of surgical
      procedures for SUI increased from 8458 to 13 219. However, the rise in the number
      of procedures in women aged over 75 was more modest-a three-fold increase from a
      low start of 187-and these women now make up a smaller proportion of all women
      receiving a mid-urethral sling (MUS). CONCLUSIONS: Despite the development and
      wide availability of a less invasive, safe and effective operation for stress
      urinary incontinence in older women, they do not appear to have benefitted. The
      reasons for this require prospective investigation.

PMID- 25752478
TI  - Determinants of trust in health care in an older population.
AB  - OBJECTIVES: To explore differences in sociodemographic and psychological
      correlates of institutional trust in health care in an aging population of
      African Americans and non-Hispanic whites. DESIGN: Cross-sectional survey data
      from the longitudinal Chicago Health and Aging Project. SETTING: Population-based
      study of three communities in the Chicago area. PARTICIPANTS: African Americans
      (n=2,284) and non-Hispanic whites (1,354) with a mean age of 79.3. MEASUREMENTS:
      Demographic factors, socioeconomic status (SES), healthcare access, cynical
      hostility, perceived discrimination, depression, and institutional trust in
      health care. RESULTS: African Americans reported substantially lower healthcare
      trust than non-Hispanic whites (P<.001). After adjustment for demographic
      variables and SES, only race (P<.001) and age (P=.008) were significantly
      associated with healthcare trust scores. The association between race and
      healthcare trust was slightly attenuated after adjusting for cynical hostility,
      depressive symptoms, and perceived discrimination (P<.001). Each of these
      variables was negatively associated with healthcare trust, and together these
      accounted for approximately 15% of racial differences in healthcare trust.
      CONCLUSION: Psychological factors, not demographic characteristics, SES, or
      healthcare factors, appear to contribute the most to disparities in healthcare
      trust between older African Americans and non-Hispanic whites.

PMID- 25752479
TI  - Convergence and divergence of genetic and modular networks between diabetes and
      breast cancer.
AB  - Diabetes mellitus (DM) and breast cancer (BC) can simultaneously occur in the
      same patient populations, but the molecular relationship between them remains
      unknown. In this study, we constructed genetic networks and used modularized
      analysis approaches to investigate the multi-dimensional characteristics of two
      diseases and one disease subtype. A text search engine (Agilent Literature Search
      2.71) and MCODE software were applied to validate potential subnetworks and to
      divide the modules, respectively. A total of 793 DM-related genes, 386 type 2
      diabetes (T2DM) genes and 873 BC-related genes were identified from the Online
      Mendelian Inheritance in Man database. For DM and BC, a total of 99 overlapping
      genes, 9 modules, 29 biological processes and 7 pathways were identified.
      Meanwhile, for T2DM and BC, 56 overlapping genes, 5 modules, 20 biological
      processes and 12 pathways were identified. Based on the Gene Ontology functional
      enrichment analysis of the top 10 non-overlapping modules of the two diseases, 10
      biological functions and 5 pathways overlapped between them. The
      glycosphingolipid and lysosome pathways verified molecular mechanisms of cell
      death related to both DM and BC. We also identified new biological functions of
      dopamine receptors and four signalling pathways (Parkinson's disease, Alzheimer's
      disease, Huntington's disease and long-term depression) related to both diseases;
      these warrant further investigation. Our results illustrate the landscape of the
      novel molecular substructures between DM and BC, which may support a new model
      for complex disease classification and rational therapies for multiple diseases. 

PMID- 25752480
TI  - Translational psychiatry--light at the end of the tunnel.
AB  - Neuroscience has made tremendous progress delineating the cellular and molecular
      processes important for understanding neuronal development and behavior, but this
      knowledge has been slow to translate to new treatments for psychiatric illness.
      To accelerate this transfer of knowledge to the human condition requires the wide
      scale adoption of biomarkers that can bridge preclinical and clinical
      discoveries, and serve as surrogate measures of efficacy before commencing
      expensive phase III studies. Several biomarker methodologies, including imaging,
      electroencephalography (EEG), and blood transcriptomics/proteomics, are now
      showing promise. From an industry perspective, we highlight the utility of
      quantitative EEG as one example of a translatable biomarker applicable to
      psychiatric drug development and discuss recent insights into glutamate system
      dysfunction in schizophrenia and depression gained through translational studies
      of the drug ketamine. 

PMID- 25752481
TI  - Melatonin induces apoptosis of colorectal cancer cells through HDAC4 nuclear
      import mediated by CaMKII inactivation.
AB  - Melatonin induces apoptosis in many different cancer cell lines, including
      colorectal cancer. However, the precise mechanisms involved remain largely
      unresolved. In this study, we provide evidence to reveal a new mechanism by which
      melatonin induces apoptosis of colorectal cancer LoVo cells. Melatonin at
      pharmacological concentrations significantly suppressed cell proliferation and
      induced apoptosis in a dose-dependent manner. The observed apoptosis was
      accompanied by the melatonin-induced dephosphorylation and nuclear import of
      histone deacetylase 4 (HDAC4). Pretreatment with a HDAC4-specific siRNA
      effectively attenuated the melatonin-induced apoptosis, indicating that nuclear
      localization of HDAC4 is required for melatonin-induced apoptosis. Moreover,
      constitutively active Ca(2+) /calmodulin-dependent protein kinase II alpha
      (CaMKIIalpha) abrogated the melatonin-induced HDAC4 nuclear import and apoptosis
      of LoVo cells. Furthermore, melatonin decreased H3 acetylation on bcl-2 promoter,
      leading to a reduction of bcl-2 expression, whereas constitutively active
      CaMKIIalpha(T286D) or HDAC4-specific siRNA abrogated the effect of melatonin. In
      conclusion, the present study provides evidence that melatonin-induced apoptosis
      in colorectal cancer LoVo cells largely depends on the nuclear import of HDAC4
      and subsequent H3 deacetylation via the inactivation of CaMKIIalpha. 

PMID- 25752482
TI  - Improving the quality and efficiency of conventional in-center hemodialysis.
AB  - There is substantial variability at international, national, and regional levels
      in how effective dialysis providers are in the implementation of well-accepted
      interventions to deliver better health outcomes at reduced costs to payers. The
      growing number of dialysis patients within a finite pool of resources has led to
      searches for more efficient methods to provide patient care without compromising
      or diminishing quality. We review here some contemporary concepts surrounding
      quality improvement and operations research that may provide clinician
      administrators to both improve efficiency and quality in facility based
      hemodialysis units. The creation of balanced scorecards, utilization of process
      mapping techniques, and the application of LEAN principles may readily improve
      how hemodialysis care is delivered in an environment of increasing patient
      volumes and reduced operating resources. 

PMID- 25752485
TI  - In Children and Youth with Mild and Moderate Traumatic Brain Injury, Glial
      Fibrillary Acidic Protein Out-Performs S100beta in Detecting Traumatic
      Intracranial Lesions on Computed Tomography.
AB  - In adults, glial fibrillary acidic protein (GFAP) has been shown to out-perform
      S100beta in detecting intracranial lesions on computed tomography (CT) in mild
      traumatic brain injury (TBI). This study examined the ability of GFAP and
      S100beta to detect intracranial lesions on CT in children and youth involved in
      trauma. This prospective cohort study enrolled a convenience sample of children
      and youth at two pediatric and one adult Level 1 trauma centers following trauma,
      including both those with and without head trauma. Serum samples were obtained
      within 6 h of injury. The primary outcome was the presence of traumatic
      intracranial lesions on CT scan. There were 155 pediatric trauma patients
      enrolled, 114 (74%) had head trauma and 41 (26%) had no head trauma. Out of the
      92 patients who had a head CT, eight (9%) had intracranial lesions. The area
      under the receiver operating characteristic curve (AUC) for distinguishing head
      trauma from no head trauma for GFAP was 0.84 (0.77-0.91) and for S100beta was
      0.64 (0.55-0.74; p<0.001). Similarly, the AUC for predicting intracranial lesions
      on CT for GFAP was 0.85 (0.72-0.98) versus 0.67 (0.50-0.85) for S100beta
      (p=0.013). Additionally, we assessed the performance of GFAP and S100beta in
      predicting intracranial lesions in children ages 10 years or younger and found
      the AUC for GFAP was 0.96 (95% confidence interval [CI] 0.86-1.00) and for
      S100beta was 0.72 (0.36-1.00). In children younger than 5 years old, the AUC for
      GFAP was 1.00 (95% CI 0.99-1.00) and for S100beta 0.62 (0.15-1.00). In this
      population with mild TBI, GFAP out-performed S100beta in detecting head trauma
      and predicting intracranial lesions on head CT. This study is among the first
      published to date to prospectively compare these two biomarkers in children and
      youth with mild TBI. 

PMID- 25752486
TI  - Phase analysis detects heterogeneity of myocardial deformation on cine MRI.
AB  - OBJECTIVES: Myocardial scar will lead to heterogeneous left ventricular
      deformation. We hypothesized that a myocardial scar will display an elevated
      standard deviation (SD) of phase and that this effect could be compared with
      mechanical dispersion. DESIGN: Thirty patients (three women and 27 men) were
      investigated over 4-8 weeks after ST-elevation myocardial infarction treated with
      percutaneous coronary intervention. Seventeen had a scar area > 75% in at least
      one antero- or inferoseptal segment (scar) and 13 had a scar area < 1% (non
      scar). The phase delays of velocity, displacement, and strain were measured in
      the longitudinal direction, tangential to the endocardial outline, and in the
      radial direction, perpendicular to the tangent. RESULTS: The SD of phase in
      radial measurements differentiated scar patients from those without scar (p <
      0.01), while longitudinal measurements did so only for longitudinal strain.
      Likewise, the SD for radial measurements of time to peak for segmental velocity,
      displacement, and strain performed better than longitudinal measurements and
      equal to the results of phase. CONCLUSION: Phase dispersion in deformation
      imaging may be used for detecting heterogeneous left ventricular contraction.

PMID- 25752487
TI  - Is There Any Difference in the Eradication Rate of Helicobacter pylori Infection
      According to the Endoscopic Stage of Peptic Ulcer Disease?
AB  - BACKGROUND: The eradication rate of Helicobacter pylori (H. pylori) infection
      might be affected by the degree of inflammation of gastric mucosa represented by
      the endoscopic stage of peptic ulcer disease (PUD). The aims of this study were
      to evaluate the eradication rates of H. pylori infection according to the
      endoscopic stage of PUD and to document whether early eradication in the active
      stage could yield a higher eradication rate in patients with peptic ulcer
      bleeding (PUB). MATERIALS AND METHODS: A total of 1,177 patients with PUD (380
      gastric ulcer, 710 duodenal ulcer, and 87 combined ulcer) who received proton
      pump inhibitor (PPI)-based triple therapy were included, and the eradication
      rates were compared by ulcer stage. Univariate and multivariate analyses were
      conducted to identify factors influencing eradication rate. In PUB, the
      eradication rates between the early eradication group (<=7 days) and the late
      eradication group (>7 days) were compared. RESULTS: The eradication rates
      according to endoscopic stage were significantly different in gastric ulcer
      (active vs healing vs scarring; 84.8% vs 82.7% vs 70.6%, p = .014, respectively),
      but there were no significant differences in duodenal ulcer (active vs healing vs
      scarring; 87.6% vs 80.9%% vs 80.9% p = .169, respectively). In multivariate
      analyses, active ulcer as well as age younger than 50 was a significantly
      independent predictor of successful eradication (Odds ratio; 2.799, 95% CI; 1.659
      4.723, p = .0001). The eradication rate of the early eradication group was
      significantly higher than the late eradication group in PUB (89.2% vs 71.9%, 95%
      CI; 1.265-8.269, p = .011). CONCLUSIONS: There was a significant difference in
      the eradication rate according to the endoscopic stage of gastric ulcer. Active
      ulcer was an independent predictor of successful eradication. Furthermore, early
      H. pylori eradication should be considered in patients with PUB to yield a higher
      eradication rate.

PMID- 25752488
TI  - Compounds for use in the treatment of mycobacterial infections: a patent
      evaluation (WO2014049107A1).
AB  - Tuberculosis is one of the main causes of mortality with 1.5 million deaths a
      year worldwide. The growing emergence of multi- and extremely resistant strains
      highlights the urgent need of novel antibiotic strategies. Ethionamide,
      interfering with the mycobacterial membrane biosynthesis, is used in second-line
      treatment. This molecule is a prodrug, which requires activation by EthA. The
      patent described in this evaluation (WO2014049107A1) claimed a new family of
      molecules and their use as antibiotic treatment against mycobacteria such as
      Mycobacterium tuberculosis, M. leprae and atypical mycobacteria, either as a
      single active agent or in combination with antibiotics activable by EthA pathway.

PMID- 25752489
TI  - Neoadjuvants for basal cell carcinoma. When and why?

PMID- 25752490
TI  - The role of gap junctions and mechanical loading on mineral formation in a
      collagen-I scaffold seeded with osteoprogenitor cells.
AB  - Fracture nonunions represent one of many large bone defects where current
      treatment strategies fall short in restoring both form and function of the
      injured tissue. In this case, the use of a tissue-engineered scaffold for
      promoting bone healing offers an accessible and easy-to-manipulate environment
      for studying bone formation processes in vitro. We have previously shown that
      mechanical prestimulation using confined compression of differentiating
      osteoblasts results in an increase in mineralization formed in a 3D collagen-I
      scaffold. This study builds on this knowledge by evaluating the short and long
      term effects of blocking gap junction-mediated intercellular communication among
      osteogenic cells on their effectiveness to mineralize collagen-I scaffolds in
      vitro, and in the presence and absence of mechanical stimulation. In this study,
      confined compression was applied in conjunction with octanol (a general
      communication blocker) or 18-alpha-glycerrhetinic acid (AGA, a specific gap
      junction blocker) using a modified FlexCell plate to collagen-I scaffolds seeded
      with murine embryonic stem cells stimulated toward osteoblast differentiation
      using beta-glycerol phosphate. The activity, presence, and expression of
      osteoblast cadherin, connexin-43, as well as various pluripotent and osteogenic
      markers were examined at 5-30 days of differentiation. Fluorescence recovery
      after photobleaching, immunofluorescence, viability, histology assessments, and
      reverse-transcriptase polymerase chain reaction assessments revealed that
      inhibiting communication in this scaffold altered the lineage and function of
      differentiating osteoblasts. In particular, treatment with communication
      inhibitors caused reduced mineralization in the matrix, and dissociation between
      connexin-43 and integrin alpha5beta1. This dissociation was not restored even
      after long-term recovery. Thus, in order for this scaffold to be considered as an
      alternative strategy for the repair of large bone defects, cell-cell contacts and
      cell-matrix interactions must remain intact for osteoblast differentiation and
      function to be preserved. This study shows that within this 3D scaffold, gap
      junctions are essential in osteoblast response to mechanical loading, and are
      essential structures in producing a significant amount and organization of
      mineralization in the matrix. 

PMID- 25752493
TI  - Hierarchically designed three-dimensional macro/mesoporous carbon frameworks for
      advanced electrochemical capacitance storage.
AB  - Mesoporous carbon (m-C) has potential applications as porous electrodes for
      electrochemical energy storage, but its applications have been severely limited
      by the inherent fragility and low electrical conductivity. A rational strategy is
      presented to construct m-C into hierarchical porous structures with high
      flexibility by using a carbon nanotube (CNT) sponge as a three-dimensional
      template, and grafting Pt nanoparticles at the m-C surface. This method involves
      several controllable steps including solution deposition of a mesoporous silica
      (m-SiO2 ) layer onto CNTs, chemical vapor deposition of acetylene, and etching of
      m-SiO2 , resulting in a CNT@m-C core-shell or a CNT@m-C@Pt core-shell hybrid
      structure after Pt adsorption. The underlying CNT network provides a robust yet
      flexible support and a high electrical conductivity, whereas the m-C provides
      large surface area, and the Pt nanoparticles improves interfacial electron and
      ion diffusion. Consequently, specific capacitances of 203 and 311 F g(-1) have
      been achieved in these CNT@m-C and CNT@m-C@Pt sponges as supercapacitor
      electrodes, respectively, which can retain 96 % of original capacitance under
      large degree compression. 

PMID- 25752492
TI  - An allosteric model for control of pore opening by substrate binding in the EutL
      microcompartment shell protein.
AB  - The ethanolamine utilization (Eut) microcompartment is a protein-based metabolic
      organelle that is strongly associated with pathogenesis in bacteria that inhabit
      the human gut. The exterior shell of this elaborate protein complex is composed
      from a few thousand copies of BMC-domain shell proteins, which form a semi
      permeable diffusion barrier that provides the interior enzymes with substrates
      and cofactors while simultaneously retaining metabolic intermediates. The ability
      of this protein shell to regulate passage of substrate and cofactor molecules is
      critical for microcompartment function, but the details of how this diffusion
      barrier can allow the passage of large cofactors while still retaining small
      intermediates remain unclear. Previous work has revealed two conformations of the
      EutL shell protein, providing substantial evidence for a gated pore that might
      allow the passage of large cofactors. Here we report structural and biophysical
      evidence to show that ethanolamine, the substrate of the Eut microcompartment,
      acts as a negative allosteric regulator of EutL pore opening. Specifically, a
      series of X-ray crystal structures of EutL from Clostridium perfringens, along
      with equilibrium binding studies, reveal that ethanolamine binds to EutL at a
      site that exists in the closed-pore conformation and which is incompatible with
      opening of the large pore for cofactor transport. The allosteric mechanism we
      propose is consistent with the cofactor requirements of the Eut microcompartment,
      leading to a new model for EutL function. Furthermore, our results suggest the
      possibility of redox modulation of the allosteric mechanism, opening potentially
      new lines of investigation.

PMID- 25752494
TI  - Determinants of Bezafibrate-induced Improvements in LDL Cholesterol in
      Dyslipidemic Patients with Diabetes.
AB  - AIM: Our previous "J-BENEFIT (Japan BEzafibrate cliNical EFfectIveness and
      Tolerability)" study demonstrated that bezafibrate improves blood lipid profiles
      and glucose control in dyslipidemic patients with diabetes. However, bezafibrate
      did not significantly improve low-density lipoprotein cholesterol (LDL-C),
      although some patients showed decreases while others showed increases in the LDL
      C levels. Therefore, a subgroup analysis of the J-BENEFIT study was conducted to
      identify factors influencing the bezafibrate-induced changes in the LDL-C levels.
      METHODS: Of the 3,316 patients in the J-BENEFIT study, 2,116 not treated with
      other lipid-lowering drugs were enrolled in the current study, and the effects of
      24-week treatment with bezafibrate on the LDL-C levels were analyzed. A reduction
      in the LDL-C level of >= 25% occurred in 253 patients, and a logistic-regression
      analysis was used to identify factors associated with this improvement. RESULTS:
      Among the 2,116 overall patients, bezafibrate treatment significantly increased
      the LDL-C levels from 123.9+/-36.7 to 125.7+/-31.3 mg/dL. The subanalysis showed
      that the treatment responses varied according to the baseline LDL-C level, with
      significant decreases in the >= 160 and >= 140-<160 mg/dL groups, no significant
      decrease in the >= 120-<140 mg/dL group and a significant increase in the <120
      mg/dL group. A multivariate logistic-regression analysis of the data for the
      patients with an LDL-C of >= 25% identified a female sex, the use of anti
      hypertensive and hypoglycemic agents and a high baseline LDL-C level to be
      significant determinants of the LDL-C response to bezafibrate. CONCLUSIONS: Our
      results showed that treatment with bezafibrate improves the LDL-C levels and
      lipid profiles in dyslipidemic diabetic patients, especially women, subjects co
      treated with anti-hypertensive or hypoglycemic agents and those with high
      baseline LDL-C levels.

PMID- 25752495
TI  - How Does Bezafibrate Affect the Plasma LDL Cholesterol Levels?

PMID- 25752496
TI  - Toll-like receptor-4 knockout mice are more resistant to optic nerve crush damage
      than wild-type mice.
AB  - BACKGROUND: This study aims to investigate the role of the inflammatory response
      following optic nerve crush (ONC) in knockout mice for the toll-like receptor-4
      gene (TLR4-/-) compared to wild-type (WT) mice. METHODS: ONC was induced in TLR4
      /- and C57BL6 WT mice. Histological sections of the retina and optic nerve were
      analysed on days 1, 3 or 21 after injury. Molecular analysis with real-time
      quantitative polymerase chain reaction was used to study the expression of CD45,
      tumour necrosis-alpha (TNF-alpha) and glial fibrillary acidic protein, as well as
      retinal ganglion cell (RGC) markers THY-1 and Brn3b. RESULTS: There was a 25.5%
      and 38% loss in the RGC layer of the ONC-injured eyes of the TLR4-/- and the WT
      mice, respectively (with 27% and 9% of the remaining cells positive for Brn3a,
      respectively). Mean levels of Thy-1 and Brn3b were higher in the TLR4-/- mice.
      CD45 and Iba1 staining revealed infiltration of inflammatory cells into the
      injured nerve and retina in both groups. Molecular analysis of the optic nerve on
      day 1 showed increased TNF-alpha expression and reduced CD45 and GFAP expression;
      on day 3, CD45 reverted to baseline but GFAP remained low; on day 21, all 3
      markers were at baseline in the TLR4-/- group and decreased in the WT group.
      CONCLUSION: Inflammation plays a major role in the response to ONC injury.
      Reduced levels of inflammation are associated with improved RGC preservation. The
      increase in TNF-alpha and reduction in CD45 in both TLR4-/- and WT mice may
      indicate the presence of an alternative pathway for induction of RGC death.

PMID- 25752497
TI  - Ten years experience with oral immunosuppressive treatment in adult patients with
      atopic dermatitis in two academic centres.
AB  - BACKGROUND: There is a lack of information on the use oral immunosuppressive
      drugs in atopic dermatitis (AD) daily practice. OBJECTIVE: A 10-years overview of
      the use of oral immunosuppressive drugs in patients with severe AD. METHODS:
      Medical charts of patients with AD, who received oral immunosuppressive drugs at
      the Academic Medical Center Amsterdam and in the University Medical Center
      Utrecht between January 2001 and January 2011, were analysed. Particular
      attention was paid to patient characteristics, prior treatment, prescribed oral
      immunosuppressive drugs, the order of use, doses and treatment durations and
      reasons for discontinuation of treatment. RESULTS: Of 334 patients [53% male,
      mean age at start of an oral immunosuppressive drug 36.9 years (SD 13.6)] with AD
      received oral immunosuppressive treatment of which 102 (31%) participated in
      clinical trials. Cyclosporine A (CyA) was given in 80% of the patients,
      mycophenolate mofetil or enteric-coated mycophenolate (MMF/EC-MPS) in 31%,
      azathioprine (AZA) in 14%, methotrexate (MTX) in 11%, systemic
      glucocorticosteroids in 7% and systemic tacrolimus in 5%. In these academic
      centra, CyA was the first choice oral immunosuppressive in 252 patients. Reasons
      for discontinuation of oral immunosuppressive drugs were controlled AD disease,
      ineffectiveness and adverse events. CONCLUSION: Various types of oral
      immunosuppressive drugs have been used over the past 10 years for the treatment
      of severe AD with a prominent first choice for CyA. Adverse events and
      ineffectiveness were frequent reasons for discontinuation. A prospective database
      of patients using oral immunosuppressive treatments in daily practice will give
      more insight in the effectiveness and safety and may help to formulate future
      recommendations.

PMID- 25752498
TI  - Chemical sterilisation of Bos indicus bull calves following intratesticular
      injection of zinc acetate: effects on semen quality and testicular changes.
AB  - The aim of this study was to determine the effects in Bos indicus bull calves of
      intratesticular administration of 1mL of either saline (n=9) or one of the two
      doses of zinc acetate (ZA1, 57.75mg, n=10 or ZA2, 71.75mg, n=10) on semen quality
      and testicular changes. Semen was collected by electroejaculation on Days 343,
      524 and 783 and animals were slaughtered on Day 860. Treatment reduced median
      maximum number of progressively motile and morphologically normal sperm collected
      (P=0.001) and the percentage of animals in which sperm were recovered (saline:
      100%, 9/9; ZA1: 44.9%, 4/9 and ZA2: 40.0%, 4/10; P=0.013). Compared to saline
      treated controls, treatment with ZA reduced the mean diameter of the testes after
      Day 34 of treatment (treatment*time, P=0.013) and total testicular weight at
      slaughter (treatment: mean+/-SEM; saline: 569.4+/-59.0g, ZA1: 249.3+/-72.9g, ZA2:
      247.5+/-68.1g; P=0.004). Histological changes in testes of bulls treated with ZA
      were characterized by germ cell depletion, vacuolation of Sertoli cells,
      interstitial fibrosis, epididymal duct atrophy with variable remnants of
      testicular tissue and degeneration. We conclude that intratesticular
      administration of two doses of ZA in B. indicus calves is able to severely impair
      spermatogenesis and cause varying degrees of testicular degeneration and a
      reduction in testicular diameter and mass. Further investigation is required to
      determine ways of obtaining more consistent results from treatment. 

PMID- 25752499
TI  - Assessment of lymphatic impairment and interstitial protein accumulation in
      patients with breast cancer treatment-related lymphedema using CEST MRI.
AB  - PURPOSE: Lymphatic impairment is known to reduce quality of life in some of the
      most crippling diseases of the 21st century, including obesity, lymphedema, and
      cancer. However, the lymphatics are not nearly as well-understood as other bodily
      systems, largely owing to a lack of sensitive imaging technologies that can be
      applied using standard clinical equipment. Here, proton exchange-weighted MRI is
      translated to the lymphatics in patients with breast cancer treatment-related
      lymphedema (BCRL). METHODS: Healthy volunteers (N = 8) and BCRL patients (N = 7)
      were scanned at 3 Tesla using customized structural MRI and amide proton transfer
      (APT) chemical exchange saturation transfer (CEST) MRI in sequence with the
      hypothesis that APT effects would be elevated in lymphedematous tissue. APT
      contrast, lymphedema stage, symptomatology, and histology information were
      evaluated. RESULTS: No significant difference between proton-weighted APT
      contrast in the right and left arms of healthy controls was observed. An increase
      in APT contrast in the affected arms of patients was found (P = 0.025; Cohen's d
      = 2.4), and variability among patients was consistent with documented damage to
      lymphatics as quantified by lymphedema stage. CONCLUSION: APT CEST MRI may have
      relevance for evaluating lymphatic impairment in patients with BCRL, and may
      extend to other pathologies where lymphatic compromise is evident.

PMID- 25752500
TI  - Spinal fusion in girls with Rett syndrome: post-operative recovery and family
      experiences.
AB  - BACKGROUND: Rett syndrome is a severe neurodevelopmental disorder mainly
      affecting females and scoliosis is a common co-morbidity. Spinal fusion may be
      recommended if the scoliosis is progressive. This qualitative study investigated
      recovery of girls with Rett syndrome during the first 12 post-operative months
      and explored family perspectives and coping around the time of surgery. METHOD:
      Parents registered with the population-based Australian Rett Syndrome Database
      were recruited to this study if their daughter had a confirmed pathogenic MECP2
      mutation and spinal fusion between 2006 and 2012. Twenty-five interviews were
      conducted to determine their daughter's recovery and parental stresses and
      coping. Themes in the interview data were identified with content analysis, and
      the regaining of gross motor skills over the first 12 post-operative months was
      described with time-to-event (survival) analysis. RESULTS: Pain and energy
      levels, appetite, mood and coinciding health issues influenced their daughter's
      post-operative recovery. The majority of girls recovered preoperative sitting
      (88%), standing (81%) and walking (80%) by 12 months. The decision to proceed
      with surgery was associated with feelings of fear, obligation, relief and guilt
      for families. Development of complications, poor support and feelings of
      isolation increased their emotional burden whereas adequate information and
      discharge preparation, confidence in self and staff, and balancing personal needs
      with their daughter's care relieved this burden. INTERPRETATION: Our study
      identified clinical practice issues in relation to families whose daughter with
      Rett syndrome undergoes spinal fusion, issues that are also relevant to other
      severe disabilities. Return of wellness and gross motor skills following spinal
      fusion in girls with Rett syndrome occurred within the first 12 post-operative
      months in most cases. Parents require information and practical support to
      alleviate their emotional burden.

PMID- 25752501
TI  - Which radionuclide, carrier molecule and clinical indication for alpha
      immunotherapy?
AB  - Beta-emitting radionuclides are not able to kill isolated tumor cells
      disseminated in the body, even if a high density of radiolabeled molecules can be
      targeted at the surface of these cells because the vast majority of emitted
      electrons deliver their energy outside the targeted cells. Alpha-particle
      emitting radionuclides may overcome this limitation. It is thus of primary
      importance to test and validate the radionuclide of choice, the most appropriate
      carrier molecule and the most promising clinical indication. Four alpha-particle
      emitting radionuclides have been or are clinically tested in phase I studies
      namely 213Bi, 225Ac, 212Pb and 211At. Clinical safety has been documented and
      encouraging efficacy has been shown for some of them (213Bi and 211At). 211At has
      been the most studied and could be the most promising radionuclide but 225Ac and
      212Pb are also of potential great interest. Any carrier molecule that has been
      labeled with beta-emitting radionuclides could be labeled with alpha particle
      emitting radionuclide using, for some of them, the same chelating agents.
      However, the physical half-life of the radionuclide should match the biological
      half-life of the radioconjugate or its catabolites. Finally everybody agrees,
      based on the quite short range of alpha particles, on the fact that the clinical
      indications for alpha-immunotherapy should be limited to the situation of
      disseminated minimal residual diseases made of small clusters of malignant cells
      or isolated tumor cells. 

PMID- 25752503
TI  - Optimization of a planar all-polymer transistor for characterization of barrier
      tissue.
AB  - The organic electrochemical transistor (OECT) is a unique device that shows great
      promise for sensing in biomedical applications such as monitoring of the
      integrity of epithelial tissue. It is a label-free sensor that is amenable to low
      cost production by roll-to-roll or other printing technologies. Herein, the
      optimization of a planar OECT for the characterization of barrier tissue is
      presented. Evaluation of surface coating, gate biocompatibility and performance,
      and optimization of the geometry of the transistor are highlighted. The
      conducting polymer poly(3,4-ethylenedioxythiophene):poly(styrene sulfonate),
      which is used as the active material in the transistor, has the added advantage
      of allowing significant light transmission compared to traditional electrode
      materials and thus permits high-quality optical microscopy. The combination of
      optical and electronic monitoring of cells shown herein provides the opportunity
      to couple two very complementary techniques to yield a low-cost method for in
      vitro cell sensing. 

PMID- 25752502
TI  - Potential of biofluid components to modify silver nanoparticle toxicity.
AB  - Establishing realistic exposure scenarios is critical for cytotoxic investigation
      of silver nanoparticles (AgNP) in the gastrointestinal tract. This study
      investigated the potential interaction with and effect of biofluid components,
      namely cholic acid, deoxycholic acid and ursodeoxycholic acid, on AgNP toxicity.
      Two cell lines corresponding to organs related to the biofluid components were
      employed. These were HepG-2 a hepatocellular carcinoma derived from liver tissue
      and Hep2 an epithelial cell line. Physiochemical and cytotoxic screening was
      performed and the ability of biofluid components to modify AgNP cytotoxicity was
      explored. No alteration to the physiochemical characteristics of AgNP by biofluid
      components was demonstrated. However, biofluid component addition resulted in
      alteration of AgNP toxicity. Greater reactive oxygen species induction was noted
      in the presence of cholic acid and deoxycholic acid. Ursodeoxycholic acid
      demonstrated no modification of toxicity in HepG-2 cells; however, significant
      modification was noted in Hep2 cells. It is concluded that biofluid components
      can modify AgNP toxicity but this is dependent on the biofluid component itself
      and the location where it acts.

PMID- 25752504
TI  - Does the correlation between Schmorl's nodes and vertebral morphology extend into
      the lumbar spine?
AB  - Schmorl's nodes are depressions on vertebrae due to herniation of the nucleus
      pulposus of the intervertebral disc into the vertebral body. This study provides
      an extension of our previous study which analyzed the shape of the lower thoracic
      spine and found that vertebral morphology was associated with the presence of
      Schmorl's nodes. Ninety adult individuals from the late Medieval site of
      Fishergate House, York, and the Post-Medieval site of Coach Lane, North Shields,
      Tyne and Wear, England, were analysed using 2D geometric morphometrics to
      identify possible relationships between vertebral morphology and Schmorl's nodes
      at the thoraco-lumbar junction and in the lumbar spine. A significant correlation
      was found between vertebral shape and the presence of Schmorl's nodes in the
      twelfth thoracic vertebrae and the first to third lumbar vertebrae. The findings
      corroborate previous studies and suggest that vertebral shape may be an important
      factor in spinal health. It is hypothesized that the pedicle shape of affected
      vertebrae may not provide adequate structural support for the vertebral bodies,
      resulting in vertical disc herniation.

PMID- 25752505
TI  - Immediate nipple reconstruction with thoracodorsal artery perforator flap in
      breast reconstruction by latissimus dorsi myocutaneous flap in patients with
      Poland's syndrome.
AB  - Loss of long-term projection is the major disadvantage of nipple reconstruction
      using local flaps. We report a technique of immediate perforator flap nipple
      reconstruction in breast reconstruction by latissimus dorsi (LD) myocutaneous
      flap in patients with Poland's syndrome. From March 2007 to July 2012, 12 female
      patients (age range, 15-21 years) underwent breast reconstructions and immediate
      nipple reconstructions. A thoracodorsal artery perforator (TAP) flap was
      simultaneously raised on the LD muscle flap and folded by itself to form the
      nipple. Both the LD flap and TAP flaps survived postoperatively. The nipple
      projection was measured by a caliper, and the average loss was 29% by the 1-year
      follow-up. Eleven patients considered the aesthetic appearance of reconstructed
      breast and nipple to be very good or good. The immediate nipple reconstruction
      with TAP flap could be safely performed and results in considerable satisfaction
      in breast reconstruction by LD myocutaneous flap in patients with Poland's
      syndrome.

PMID- 25752506
TI  - A subpopulation of CD103(pos) ICOS(pos) Treg cells occurs at high frequency in
      lymphopenic mice and represents a lymph node specific differentiation stage.
AB  - Regulatory T (Treg) cells are pivotal for the maintenance of peripheral tolerance
      by controlling self-reactive, chronic, and homeostatic T-cell responses. Here, we
      report that the increase in Treg-cell suppressive function observed in
      lymphopenic mice correlates with the degree of lymphopenia and is caused by a
      higher frequency of a novel subpopulation of CD103(pos) ICOS(pos) Treg cells.
      Though present in the thymus, CD103(pos) ICOS(pos) Treg cells are not generated
      there but recirculate from the periphery to that site. The acquisition and
      maintenance of this distinctive phenotype requires the LN microenvironment and
      the in situ availability of antigen. Contrary to conventional effector and other
      Treg cells, the cellularity of CD103(pos) ICOS(pos) Treg cells is not affected by
      the absence of IL-7 and thymic stroma lymphopoetin. Given their increased
      frequency in lymphopenia, the absolute number of CD103(pos) ICOS(pos) Treg cells
      remains unchanged in the periphery irrespective of a paucity of total Treg cells.
      We furthermore demonstrate, with cell transfers in mice, that the CD103(pos)
      ICOS(pos) phenotype represents a LN-specific differentiation stage arrived at by
      several other Treg-cell subsets. Thus, tissue-specific cues determine the overall
      potency of the peripheral Treg-cell pool by shaping its subset composition. 

PMID- 25752507
TI  - Predictors and costs of readmissions at an academic head and neck surgery
      service.
AB  - BACKGROUND: Health care metrics, such as readmission rates, are being scrutinized
      to improve quality and decrease cost of care. The purpose of this study was to
      determine the rate, predictors, and costs of 30-day unplanned readmissions
      (30dURs) in patients who undergo head and neck surgery. METHODS: All patients
      undergoing head and neck surgery at the Ohio State University from July 1, 2011,
      to June 30, 2012, were retrospectively reviewed. Univariate and multivariate
      logistic regression analyses were performed to identify risk factors for 30dURs.
      RESULTS: ?Six hundred seven patients underwent 660 operations. Forty-eight cases
      (7.3%) had a 30dUR. Significant independent risk factors for readmissions
      included: coronary artery disease (odds ratio [OR] = 2.80; confidence interval
      [CI] = 1.3-5.9), chronic renal failure (OR = 3.56; CI = 1.5-8.5), not attending
      the preoperative clinic (OR = 2.74; CI = 1.2-6.3), length of stay (LOS) >5 days
      (OR = 3.19; CI = 1.6-6.5), and presence of a gastrostomy tube (OR = 2.75; CI =
      1.3-5.8).The total cost of 30dURs was $1.68 million. CONCLUSION: The 30dURs in
      patients who undergo head and neck surgery can be low, but costly. Identifying
      patients at risk for 30dUR will help develop preventative strategies. (c) 2015
      Wiley Periodicals, Inc. Head Neck 38: E502-E510, 2016.

PMID- 25752508
TI  - Phenological plasticity will not help all species adapt to climate change.
AB  - Concerns are rising about the capacity of species to adapt quickly enough to
      climate change. In long-lived organisms such as trees, genetic adaptation is
      slow, and how much phenotypic plasticity can help them cope with climate change
      remains largely unknown. Here, we assess whether, where and when phenological
      plasticity is and will be adaptive in three major European tree species. We use a
      process-based species distribution model, parameterized with extensive ecological
      data, and manipulate plasticity to suppress phenological variations due to
      interannual, geographical and trend climate variability, under current and
      projected climatic conditions. We show that phenological plasticity is not always
      adaptive and mostly affects fitness at the margins of the species' distribution
      and climatic niche. Under current climatic conditions, phenological plasticity
      constrains the northern range limit of oak and beech and the southern range limit
      of pine. Under future climatic conditions, phenological plasticity becomes
      strongly adaptive towards the trailing edges of beech and oak, but severely
      constrains the range and niche of pine. Our results call for caution when
      interpreting geographical variation in trait means as adaptive, and strongly
      point towards species distribution models explicitly taking phenotypic plasticity
      into account when forecasting species distribution under climate change
      scenarios. 

PMID- 25752509
TI  - Regulation of CYBB Gene Expression in Human Phagocytes by a Distant Upstream NF
      kappaB Binding Site.
AB  - The human CYBB gene encodes the gp91-phox component of the phagocyte oxidase
      enzyme complex, which is responsible for generating superoxide and other
      downstream reactive oxygen species essential to microbial killing. In the present
      study, we have identified by sequence analysis a putative NF-kappaB binding site
      in a DNase I hypersensitive site, termed HS-II, located in the distant 5'
      flanking region of the CYBB gene. Electrophoretic mobility assays showed binding
      of the sequence element by recombinant NF-kappaB protein p50 and by proteins in
      nuclear extract from the HL-60 myeloid leukemia cell line corresponding to p50
      and to p50/p65 heterodimers. Chromatin immunoprecipitation demonstrated NF-kappaB
      binding to the site in intact HL-60 cells. Chromosome conformation capture (3C)
      assays demonstrated physical interaction between the NF-kappaB binding site and
      the CYBB promoter region. Inhibition of NF-kappaB activity by salicylate reduced
      CYBB expression in peripheral blood neutrophils and differentiated U937 monocytic
      leukemia cells. U937 cells transfected with a mutant inhibitor of kappaB "super
      repressor" showed markedly diminished CYBB expression. Luciferase reporter
      analysis of the NF-kappaB site linked to the CYBB 5' flanking promoter region
      revealed enhanced expression, augmented by treatment with interferon-gamma. These
      studies indicate a role for this distant, 15 kb upstream, binding site in NF
      kappaB regulation of the CYBB gene, an essential component of phagocyte-mediated
      host defense.

PMID- 25752510
TI  - Cardiosphere-derived cells from pediatric end-stage heart failure patients have
      enhanced functional activity due to the heat shock response regulating the
      secretome.
AB  - We have demonstrated that human neonatal cardiosphere-derived cells (CDCs)
      derived from the young are more regenerative due to their robust secretome.
      However, it is unclear how the decompensated pediatric heart impacts the
      functional activity of their CDCs. Our aim was to characterize the potency of
      pediatric CDCs derived from normal functioning myocardium of control heart
      disease (CHD) patients to those generated from age-matched end stage heart
      failure (ESHF) patients and to determine the mechanisms involved. ESHF-derived
      CDCs contained a higher number of c-kit(+) , Islet-1(+) , and Sca-1(+) cells.
      When transplanted into an infarcted rodent model, ESHF-derived CDCs significantly
      demonstrated higher restoration of ventricular function, prevented adverse
      remodeling, and enhanced angiogenesis when compared with CHD patients. The
      superior functional recovery of the ESHF-derived CDCs was mediated in part by
      increased SDF-1alpha and VEGF-A secretion resulting in augmented recruitment of
      endogenous stem cells and proliferation of cardiomyocytes. We determined the
      mechanism is due to the secretome directed by the heat shock response (HSR),
      which is supported by three lines of evidence. First, gain of function studies
      demonstrated that increased HSR induced the lower functioning CHD-derived CDCs to
      significantly restore myocardial function. Second, loss-of function studies
      targeting the HSR impaired the ability of the ESHF-derived CDCs to functionally
      recover the injured myocardium. Finally, the native ESHF myocardium had an
      increased number of c-kit(+) cardiac stem cells. These findings suggest that the
      HSR enhances the functional activity of ESHF-derived CDCs by increasing their
      secretome activity, notably SDF-1alpha and VEGF-A.

PMID- 25752511
TI  - Bullying, abuse and family conflict as risk factors for chronic pain among Dutch
      adolescents.
AB  - PURPOSE: Psychosocial stress seems to serve as an important risk factor for the
      occurrence of pain. The present study aims to examine if early adversities, e.g.
      bullying, abuse and family conflict are risk factors for chronic pain in
      adolescents. The secondary aim of the present study was to describe the pain
      characteristics of chronic pain in adolescents in a community sample of Dutch
      adolescents. METHODS: Participants in the present study were 15,220 adolescents,
      attending schools (grade 7 and 8) in Rotterdam, the Netherlands. Chronic pain was
      measured with a newly developed questionnaire; the Pain Barometer. Early
      adversities were measured using single-item questions from the Rotterdam Youth
      Monitor, a longitudinal youth health surveillance system. Cross-sectional
      associations between early adversities and chronic pain were investigated using
      logistic multilevel analysis, adjusted for potential confounding. RESULTS: In
      school year 2010-2011, 9.2% of the 15,220 adolescents reported chronic pain.
      Physical abuse by others (OR = 1.51, 95% CI =  1.07-2.14), sexual abuse (OR =
      1.46, 95% CI = 1.05-2.05), family conflict (OR = 1.79, 95% C = 1.61-1.99) and
      being bullied (OR = 1.23, 95% CI = 1.17-1.29) are more common in adolescents with
      chronic pain. Physical abuse (OR = 1.28, 95% CI = 0.95-1.71) by parents and
      parental divorce (OR = 1.07, 95% CI = 0.93-1.22) were not significantly related
      to chronic pain. CONCLUSIONS: The results of the present study suggest that
      bullying, abuse and family conflict may be risk factors for chronic pain in
      adolescents. Early signalling these stressors might prevent chronic pain.
      IMPLICATIONS AND CONTRIBUTION: Early adversities, i.e. physical and sexual abuse,
      being bullied and family conflict, might be risk factors for developing chronic
      pain. In addition, the present study suggests that chronic pain is common among
      Dutch adolescents and interferes with their daily activities. If future studies
      confirm our results, this knowledge can be used to improve the signalling and
      prevention of chronic pain in adolescents.

PMID- 25752512
TI  - Cinnamaldehyde promotes root branching by regulating endogenous hydrogen sulfide.
AB  - BACKGROUND: Cinnamaldehyde (CA) has been widely applied in medicine and food
      preservation. However, whether and how CA regulates plant physiology is largely
      unknown. To address these gaps, the present study investigated the beneficial
      effect of CA on root branching and its possible biochemical mechanism. RESULTS:
      The lateral root (LR) formation of pepper seedlings could be markedly induced by
      CA at specific concentrations without any inhibitory effect on primary root (PR)
      growth. CA could induce the generation of endogenous hydrogen sulfide (H2S) by
      increasing the activity of L-cysteine desulfhydrase in roots. By fluorescently
      tracking endogenous H2S in situ, it could be clearly observed that H2S
      accumulated in the outer layer cells of the PR where LRs emerge. Sodium
      hydrosulfide (H2S donor) treatment induced LR formation, while hypotaurine (H2S
      scavenger) showed an adverse effect. The addition of hypotaurine mitigated the CA
      induced increase in endogenous H2S level, which in turn counteracted the
      inducible effect of CA on LR formation. CONCLUSION: CA showed great potential in
      promoting LR formation, which was mediated by endogenous H2S. These results not
      only shed new light on the application of CA in agriculture but also extend the
      knowledge of H2S signaling in the regulation of root branching.

PMID- 25752513
TI  - Combined dielectrophoretic and impedance system for on-chip controlled bacteria
      concentration: Application to Escherichia coli.
AB  - The present paper reports a bacteria autonomous controlled concentrator prototype
      with a user-friendly interface for bench-top applications. It is based on a
      microfluidic lab-on-a-chip and its associated custom instrumentation, which
      consists of a dielectrophoretic actuator, to preconcentrate the sample, and an
      impedance analyzer, to measure concentrated bacteria levels. The system is
      composed of a single microfluidic chamber with interdigitated electrodes and an
      instrumentation with custom electronics. The prototype is supported by a real
      time platform connected to a remote computer, which automatically controls the
      system and displays impedance data used to monitor the status of bacteria
      accumulation on-chip. The system automates the whole concentrating operation.
      Performance has been studied for controlled volumes of Escherichia coli samples
      injected into the microfluidic chip at constant flow rate of 10 MUL/min. A media
      conductivity correcting protocol has been developed, as the preliminary results
      showed distortion of the impedance analyzer measurement produced by bacterial
      media conductivity variations through time. With the correcting protocol, the
      measured impedance values were related to the quantity of bacteria concentrated
      with a correlation of 0.988 and a coefficient of variation of 3.1%. Feasibility
      of E. coli on-chip automated concentration, using the miniaturized system, has
      been demonstrated. Furthermore, the impedance monitoring protocol had been
      adjusted and optimized, to handle changes in the electrical properties of the
      bacteria media over time. 

PMID- 25752514
TI  - Simultaneous Visualization of Multiple mRNAs and Matrix Metalloproteinases in
      Living Cells Using a Fluorescence Nanoprobe.
AB  - Simultaneous monitoring of multiple tumour markers is of great significance for
      improving the accuracy of early cancer detection. In this study, a fluorescence
      nanoprobe has been prepared that can simultaneously monitor and visualize
      multiple mRNAs and matrix metalloproteinases (MMPs) in living cells. Confocal
      fluorescence imaging results indicate that the nanoprobe could effectively
      distinguish between cancer cells and normal cells even if one tumour maker of
      normal cells was overexpressed. Furthermore, it can detect changes in the
      expression levels of mRNAs and MMPs in living cells. The current approach could
      provide new tools for early cancer detection and monitoring the changes in
      expression levels of biomarkers during tumour progression. 

PMID- 25752515
TI  - beta-Arrestin2 Contributes to Cell Viability and Proliferation via the Down
      Regulation of FOXO1 in Castration-Resistant Prostate Cancer.
AB  - beta-Arrestin2 has been identified to act as a corepressor of androgen receptor
      (AR) signaling by binding to AR and serving as a scaffold to affect the activity
      and expression of AR in androgen-dependent prostate cancer cells; however, little
      is known regarding its role in castration-resistant prostate cancer (CRPC)
      progression. Here, our data demonstrated that beta-arrestin2 contributes to the
      cell viability and proliferation of CRPC via the downregulation of FOXO1 activity
      and expression. Mechanistically, in addition to its requirement for FOXO1
      phosphorylation induced by IGF-1, beta-arrestin2 could inhibit FOXO1 activity in
      an Akt-independent manner and delay FOXO1 dephosphorylation through the
      inhibition of PP2A phosphatase activity and the attenuation of the interaction
      between FOXO1 and PP2A. Furthermore, beta-arrestin2 could downregulate FOXO1
      expression via ubiquitylation and proteasomal degradation. Together, our results
      identified a novel role for beta-arrestin2 in the modulation of the CRPC progress
      through FOXO1. Thus, the characterization of beta-arrestin2 may represent an
      alternative therapeutic target for CRPC treatment.

PMID- 25752516
TI  - Photochemical CO2-reduction catalyzed by mono- and dinuclear phenanthroline
      extended tetramesityl porphyrin complexes.
AB  - We here present a comprehensive study on the light-induced catalytic CO2
      reduction employing a number of mono- and dinuclear complexes with a
      phenanthroline-extended tetramesityl porphyrin ligand (). A stepwise synthesis of
      heterodinuclear complexes is possible because the phenanthroline moiety of the
      ligand can selectively coordinate a second metal center, e.g. Ru(tbbpy)2(2+)
      fragment, while any other metal can reside in the porphyrin cavity. We expanded
      our former studies to cobalt and iron compounds and synthesized the complexes ,
      and , . Thorough catalytic investigation on the light-driven CO2 reduction of all
      compounds (M = 2H, Cu, Pd, Co, FeCl) was performed in a DMF solution in the
      presence of triethylamine (TEA) as a sacrificial electron donor. A very
      surprising wavelength dependence of the catalytic performance was observed.
      Turnover numbers (TONs) of CO were quantified and showed that redox active metals
      (i.e.M = Co and FeCl) in the porphyrin cavity caused the highest catalytic
      activity. After 24 hours of illumination with light lambda > 305 nm reached a
      TONCO of 11.4 with our experimental setup without showing much decomposition.
      This value is twice as high as the TONCO determined for CoTPP (5.8) under the
      same conditions, which represented the most active porphyrinic system so far for
      photocatalytic CO2 reduction. 

PMID- 25752517
TI  - Transcriptional control of neural crest specification into peripheral glia.
AB  - The neural crest is a transient migratory multipotent cell population that
      originates from the neural plate border and is formed at the end of gastrulation
      and during neurulation in vertebrate embryos. These cells give rise to many
      different cell types of the body such as chondrocytes, smooth muscle cells,
      endocrine cells, melanocytes, and cells of the peripheral nervous system
      including different subtypes of neurons and peripheral glia. Acquisition of
      lineage-specific markers occurs before or during migration and/or at final
      destination. What are the mechanisms that direct specification of neural crest
      cells into a specific lineage and how do neural crest cells decide on a specific
      migration route? Those are fascinating and complex questions that have existed
      for decades and are still in the research focus of developmental biologists. This
      review discusses transcriptional events and regulations occurring in neural crest
      cells and derived lineages, which control specification of peripheral glia,
      namely Schwann cell precursors that interact with peripheral axons and further
      differentiate into myelinating or nonmyelinating Schwann cells, satellite cells
      that remain tightly associated with neuronal cell bodies in sensory and
      autonomous ganglia, and olfactory ensheathing cells that wrap olfactory axons,
      both at the periphery in the olfactory mucosa and in the central nervous system
      in the olfactory bulb. Markers of the different peripheral glia lineages
      including intermediate multipotent cells such as boundary cap cells, as well as
      the functions of these specific markers, are also reviewed. Enteric ganglia,
      another type of peripheral glia, will not be discussed in this review. GLIA
      2015;63:1883-1896.

PMID- 25752519
TI  - Prehospital trauma arrival notification associated with more image studies in
      patients with minor head trauma discharged from ED.
AB  - OBJECTIVES: The objective of this study was to determine whether prehospital
      trauma arrival notification was associated with more head computed tomography
      (CT) scans and image studies performed in patients with minor head trauma and
      discharged from emergency department (ED). METHODS: A retrospective cross
      sectional study based on hospital electronic medical record was performed.
      Patients with head trauma indicated by their diagnostic codes or chief
      complaints, presenting to and discharged from ED in a level I trauma center
      between January 1, 2010, and June 30, 2014, and triage Glasgow Coma Scale (GCS)
      score 14 or greater were selected from electronic medical record. Triage
      prehospital trauma arrival notification, number and types of image studies
      performed, and basic demographics were extracted. chi(2) Analysis (or Fisher
      test) was applied to compare the proportions of patients who received image
      studies between prehospital trauma arrival notification and non-notification
      groups. RESULTS: There were 3603 patients with head trauma, triage GCS score 14
      or greater, and discharged from ED. Mean age was 43.8 years. Forty-six percent
      was female. Thirty-two point nine percent was Hispanic, and 28.6% was black.
      Numbers (proportions) of patients who received prehospital trauma arrival
      notification, head CT scan, or any image study (x-ray, CT, magnetic resonance
      imaging, or sonogram) were 287 (8.0%), 1621 (45.0%), and 2267 (63.0%),
      respectively. Compared with patients without prehospital trauma arrival
      notifications, patients with prehospital trauma arrival notifications were
      significantly more likely to receive a head CT scan as well as an image study.
      CONCLUSIONS: Prehospital trauma arrival notification was associated with
      significantly more head CT scans and more image studies in patients with minor
      head trauma and discharged from ED.

PMID- 25752518
TI  - Impaired increases in skin sympathetic nerve activity contribute to age-related
      decrements in reflex cutaneous vasoconstriction.
AB  - KEY POINTS: The reduction in skin blood flow during whole-body cooling is
      impaired in healthy older adults. However, the relative contributions of altered
      skin sympathetic nerve activity (SSNA), transduction of this efferent neural
      outflow to the cutaneous vasculature, and peripheral vascular responsiveness to
      adrenergic stimuli to the impaired reflex vasoconstrictor response to whole-body
      cooling in human ageing remain unclear. We report that the SSNA response to whole
      body cooling is blunted in healthy older adults, and this attenuated sympathetic
      response is related to a marked impairment in reflex cutaneous vasoconstriction.
      Further, the reflex SSNA response to a non-thermoregulatory stimulus was
      preserved in older adults during cooling. We additionally show that cutaneous
      vascular responsiveness to adrenergic stimuli is not reduced in older adults.
      These results further our understanding of the physiological mechanisms
      underlying impaired thermal-cardiovascular integration in healthy ageing.
      ABSTRACT: Reflex cutaneous vasoconstriction is impaired in older adults; however,
      the relative roles of altered skin sympathetic nerve activity (SSNA) and end
      organ peripheral vascular responsiveness are unclear. We hypothesized that in
      older adults whole-body cooling would elicit a blunted SSNA response and
      cutaneous adrenergic responsiveness would be reduced. Twelve young adults (Y; 24
      +/- 1 years) and 12 older adults (O; 57 +/- 2 years) participated in two
      protocols. In Protocol 1, SSNA (peroneal microneurography) and red cell flux in
      the affected dermatome (laser Doppler flowmetry; dorsum of foot) were measured
      during whole-body cooling (mean skin temperature (Tsk ) 30.5 degrees C; water
      perfused suit). Mental stress was performed at mean Tsk 34.0 degrees C
      (thermoneutral) and at 30.5 degrees C. In Protocol 2, an intradermal
      microdialysis fibre was placed in the skin of the lateral calf for graded
      infusions of noradrenaline (norepinephrine) (NA; 10(-12) to 10(-2)  m). Cutaneous
      vascular conductance (CVC = flux/mean arterial pressure) was expressed as a
      change from baseline (DeltaCVCbase ). Vasoconstriction was attenuated in O. SSNA
      increased significantly during cooling in Y (+184 +/- 37%; P < 0.05) but not O
      (+51 +/- 12%; P > 0.05). Mental stress at Tsk 30.5 degrees C further increased
      SSNA in both groups. There was no age-related difference in adrenergic
      responsiveness to exogenous NA (logEC50 : -6.41 +/- 0.24 in Y, -6.37 +/- 0.25 in
      O; P > 0.05). While the SSNA response to whole-body cooling is impaired with
      ageing, SSNA can be further increased by a non-thermoregulatory stimulus.
      Cutaneous adrenergic sensitivity is not reduced in O. These findings suggest that
      alterations in afferent signalling or central processing likely contribute to
      blunted SSNA responses to cooling and subsequent impairments in reflex cutaneous
      vasoconstriction in ageing.

PMID- 25752520
TI  - The pharmacogenetics of codeine pain relief in the postpartum period.
AB  - The objective of this study was to examine interindividual variability in codeine
      requirements and pain management by examining select genetic polymorphisms in the
      codeine pharmacological pathway. The study included a nested cohort of 98 women
      who were prescribed codeine following cesarean section. Participants were
      genotyped for select polymorphisms of the COMT, ABCB1, CYP2D6, UGT2B7 and OPRM1
      genes and instructed to describe their level of pain using the visual analog
      scale (mm) 1 h following each dose of codeine. Analysis revealed that reported
      pain increases with maternal age (P=0.041). Asians required more codeine than
      Caucasians (P=0.048). Significant differences in mean dose consumption were seen
      among the genotypic groups of the OPRM1 A118G (P=0.001) and UGT2B7 C802T
      (P=0.015) variants. These variants were found to predict codeine consumption in
      the cohort overall (P=0.000) and among Caucasians (P=0.001). These findings will
      assist in customizing therapy to effectively manage postpartum pain.

PMID- 25752521
TI  - Tag SNPs for HLA-B alleles that are associated with drug response and disease
      risk in the Chinese Han population.
AB  - Multiple HLA-B alleles (haplotypes) are associated with drug-induced adverse
      responses and disease risks but are difficult to be directly genotyped. The goal
      of this study is to identify single nucleotide polymorphisms (SNPs) that are able
      to tag HLA-B alleles in the Chinese Han population. Twelve HLA-B alleles that are
      associated with drug adverse responses and disease risks were identified. They
      were sequenced initially in 880 Chinese Han subjects where high-density SNPs
      within the HLA-B gene were available. Performances of these SNPs to tag the HLA-B
      alleles were assessed primarily by sensitivity and specificity. Two HLA-B alleles
      can be reliably tagged by SNPs at 100% sensitivity and >95% specificity. For
      example, HLA-B*15:02 can be tagged by the 'C' allele of rs10484555, and HLA
      B*58:01 can be tagged by the 'T' allele of rs9262570. These results were
      confirmed in 500 additional Chinese Han subjects. If confirmed in independent
      studies, these tag SNPs could be used as a reliable, simple and cost-effective
      alternative for genotyping a subset of HLA-B alleles.

PMID- 25752524
TI  - Competition between surface modification and abrasive polishing: a method of
      controlling the surface atomic structure of 4H-SiC (0001).
AB  - The surface atomic step-terrace structure of 4H-SiC greatly affects its
      performance in power device applications. On the basis of the crystal structure
      of 4H-SiC, we propose the generation mechanism of the a-b-a*-b* type, a-b type
      and a-a type step-terrace structures. We demonstrate that the step-terrace
      structure of SiC can be controlled by adjusting the balance between chemical
      modification and physical removal in CeO2 slurry polishing. When chemical
      modification plays the main role in the polishing of SiC, the a-b-a*-b* type step
      terrace structure can be generated. When the roles of physical removal and
      chemical modification have similar importance, the a-b-a*-b* type step-terrace
      structure changes to the a-b type. When physical removal is dominant, the uniform
      a-a type step-terrace structure can be generated. 

PMID- 25752522
TI  - Variations in genes involved in immune response checkpoints and association with
      outcomes in patients with resected colorectal liver metastases.
AB  - In patients with colorectal liver metastases (CLM), liver resection offers the
      possibility of cure and long-term survival. The liver is a highly immunogenic
      organ harboring ~80% of the body's tissue macrophages. Emerging data demonstrate
      a critical role of the immune response for cancer treatment. We investigated
      variations within genes involved in immune response checkpoints and their
      association with outcomes in patients with CLM who underwent neoadjuvant
      chemotherapy including bevacizumab and liver resection. Single-nucleotide
      polymorphisms (SNPs) in nine genes (CCL2, CCR2, LAG3, NT5E, PDCD1, CD274, IDO1,
      CTLA4 and CD24) were analyzed in genomic DNA from 149 patients with resected
      bevacizumab-pretreated CLM by direct Sanger DNA sequencing, and correlated with
      response, recurrence-free survival (RFS), overall survival (OS), probability of
      cure and recurrence patterns. IDO1 (indoleamine 2, 3-dioxygenase) rs3739319 G>A
      and CD24 rs8734 G>A showed a significant difference in 3-year OS rates. In
      addition, IDO1 rs3739319 G>A was significantly associated with extrahepatic
      recurrence. Recursive partitioning analyses revealed that IDO1 rs3739319 G>A was
      the dominant SNP predicting RFS and OS. Our data suggest that variants within
      genes involved in immune response checkpoints are associated with outcomes in
      patients with resected CLM and might lead to improved treatment strategies
      modulating anti-tumor immune response by targeting novel immune checkpoints.

PMID- 25752523
TI  - Exome sequencing and array-based comparative genomic hybridisation analysis of
      preferential 6-methylmercaptopurine producers.
AB  - Preferential conversion of azathioprine or 6-mercaptopurine into methylated
      metabolites is a major cause of thiopurine resistance. To seek potentially
      Mendelian causes of thiopurine hypermethylation, we recruited 12 individuals who
      exhibited extreme therapeutic resistance while taking azathioprine or 6
      mercaptopurine and performed whole-exome sequencing (WES) and copy-number variant
      analysis by array-based comparative genomic hybridisation (aCGH). Exome-wide
      variant filtering highlighted four genes potentially associated with thiopurine
      metabolism (ENOSF1 and NFS1), transport (SLC17A4) or therapeutic action (RCC2).
      However, variants of each gene were found only in two or three patients, and it
      is unclear whether these genes could influence thiopurine hypermethylation.
      Analysis by aCGH did not identify any unusual or pathogenic copy-number variants.
      This suggests that if causative mutations for the hypermethylation phenotype
      exist they may be heterogeneous, occurring in several different genes, or they
      may lie within regulatory regions not captured by WES. Alternatively,
      hypermethylation may arise from the involvement of multiple genes with small
      effects. To test this hypothesis would require recruitment of large patient
      samples and application of genome-wide association studies.

PMID- 25752525
TI  - Phenolic thio- and selenosemicarbazones as multi-target drugs.
AB  - A series of isosteric phenolic thio- and selenosemicarbazones have been obtained
      by condensation of naturally-occurring phenolic aldehydes and
      thio(seleno)semicarbazides. Title compounds were designed as potential multi
      target drugs, and a series of structure-activity relationships could be
      established upon their in vitro assays: antioxidant activity, alpha-glucosidase
      inhibition and antiproliferative activity against six human tumor cell lines:
      A549 (non-small cell lung), HBL-100 (breast), HeLa (cervix), SW1573 (non-small
      cell lung), T-47D (breast) and WiDr (colon). For the antiradical activity,
      selenium atom and 2 or 3 phenolic hydroxyl groups proved to be essential motifs;
      remarkably, the compound with the most potent activity, with a trihydroxyphenyl
      scaffold (EC50 = 4.87 +/- 1.57 MUM) was found to be stronger than natural
      hydroxytyrosol, a potent antioxidant present in olive oil (EC50 = 13.80 +/- 1.41
      MUM). Furthermore, one of the thiosemicarbazones was found to be a strong non
      competitive inhibitor of alpha-glucosidase (Ki = 9.6 +/- 1.6 MUM), with an 8-fold
      increase in activity compared to acarbose (Ki = 77.9 +/- 11.4 MUM), marketed for
      the treatment of type-2 diabetes. Most of the synthesized compounds also
      exhibited relevant antiproliferative activities; in particular, seleno
      derivatives showed GI50 values lower than 6.0 MUM for all the tested cell lines;
      N-naphthyl mono- and dihydroxylated derivatives behaved as more potent
      antiproliferative agents than 5-fluorouracil or cisplatin.

PMID- 25752526
TI  - A few atoms make the difference: synthetic, CD, NMR and computational studies on
      antiviral and antibacterial activities of glycopeptide antibiotic aglycon
      derivatives.
AB  - Despite the close structural similarity between the heptapeptide cores of the
      glycopeptide antibiotics teicoplanin and ristocetin, synthetically modified
      derivatives of their aglycons show significantly different antibacterial and
      antiviral properties. The teicoplanin aglycon derivatives with one exception
      proved to be potent antibacterials but they did not exhibit anti-influenza virus
      activity. In contrast, the aglycoristocetin derivatives generally showed high
      anti-influenza virus activity and possessed moderate antibacterial activity. A
      systematic structure-activity relationship study has been carried out on
      ristocetin and teicoplanin aglycon derivatives, to explore which structural
      differences are responsible for these markedly different biological activities.
      According to electronic circular dichroism and in silico conformational studies,
      it was found that the differences in anti-influenza virus activity are mainly
      determined by the conformation of the heptapeptide core of the antibiotics
      controlled by the presence or absence of chloro substituents. Knowledge of the
      bioactive conformation will help to design new analogs with improved anti
      influenza virus activity. For the teicoplanin derivatives, it was shown that
      derivatization to improve the antiviral efficacy was accompanied by a significant
      decrease in antibacterial activity. 

PMID- 25752527
TI  - Use of the CRISPR/Cas9 system as an intracellular defense against HIV-1 infection
      in human cells.
AB  - To combat hostile viruses, bacteria and archaea have evolved a unique antiviral
      defense system composed of clustered regularly interspaced short palindromic
      repeats (CRISPRs), together with CRISPR-associated genes (Cas). The CRISPR/Cas9
      system develops an adaptive immune resistance to foreign plasmids and viruses by
      creating site-specific DNA double-stranded breaks (DSBs). Here we adapt the
      CRISPR/Cas9 system to human cells for intracellular defense against foreign DNA
      and viruses. Using HIV-1 infection as a model, our results demonstrate that the
      CRISPR/Cas9 system disrupts latently integrated viral genome and provides long
      term adaptive defense against new viral infection, expression and replication in
      human cells. We show that engineered human-induced pluripotent stem cells stably
      expressing HIV-targeted CRISPR/Cas9 can be efficiently differentiated into HIV
      reservoir cell types and maintain their resistance to HIV-1 challenge. These
      results unveil the potential of the CRISPR/Cas9 system as a new therapeutic
      strategy against viral infections. 

PMID- 25752528
TI  - Nicotinic acid is a common regulator of heat-sensing TRPV1-4 ion channels.
AB  - Nicotinic acid (NA, a.k.a. vitamin B3 or niacin) can reduce blood cholesterol and
      low-density lipoproteins whereas increase high-density lipoproteins. However,
      when NA is used to treat dyslipidemias, it causes a strong side effect of
      cutaneous vasodilation, commonly called flushing. A recent study showed that NA
      may cause flushing by lowering activation threshold temperature of the heat
      sensitive capsaicin receptor TRPV1 ion channel, leading to its activation at body
      temperature. The finding calls into question whether NA might also interact with
      the homologous heat-sensitive TRPV2-4 channels, particularly given that TRPV3 and
      TRPV4 are abundantly expressed in keratinocytes of the skin where much of the
      flushing response occurs. We found that NA indeed potentiated TRPV3 while
      inhibited TRPV2 and TRPV4. Consistent with these gating effects, NA lowered the
      heat-activation threshold of TRPV3 but elevated that of TRPV4. We further found
      that activity of TRPV1 was substantially prolonged by extracellular NA, which may
      further enhance the direct activation effect. Consistent with the broad gating
      effect on TRPV1-4 channels, evidence from the present study hints that NA may
      share the same activation pathway as 2-aminoethoxydiphenyl borate (2-APB), a
      common agonist for these TRPV channels. These findings shed new light on the
      molecular mechanism underlying NA regulation of TRPV channels. 

PMID- 25752529
TI  - Biotechnology: Making a meal of RNA.

PMID- 25752532
TI  - Water protection in the Baltic Sea and the Chesapeake Bay: institutions, policies
      and efficiency.
AB  - The Baltic Sea and the Chesapeake Bay share many characteristics. Both are
      shallow, brackish marine areas that suffer from eutrophication. Successful
      policies targeting point source pollution have lowered nutrient loads in both
      areas, but achieving the desired marine quality will require further abatement:
      efforts may be extended to more complicated and expensive pollution sources,
      notably agricultural nonpoint loads. Despite their ecological similarities, the
      two watersheds have different histories and institutional settings and have thus
      adopted different policies. Comparing and contrasting the policies reveal ways to
      improve the efficiency of each and ways to avoid the path of trial and error. No
      comparison of the parallel protection efforts, which involve expenditures of
      hundreds of millions of dollars annually, has been carried out to date. The
      present paper analyzes the policies applied in the two regions, distilling the
      results into six recommendations for future steps in preserving what are valuable
      sea areas. 

PMID- 25752531
TI  - Corals persisting in naturally turbid waters adjacent to a pristine catchment in
      Solomon Islands.
AB  - Few water quality measurements exist from pristine environments, with fewer
      reported studies of coastal water quality from Solomon Islands. Water quality
      benchmarks for the Solomons have relied on data from other geographic regions,
      often from quite different higher latitude developed nations, with large land
      masses. We present the first data of inshore turbidity and sedimentation rate for
      a pristine catchment on Isabel Island. Surveys recorded relatively high coral
      cover. The lowest cover was recorded at 22.7% (Jejevo) despite this site having a
      mean turbidity (continuous monitoring) of 32 NTU. However, a similar site (Jihro)
      was significantly less turbid (2.1 mean NTU) over the same period. This
      difference in turbidity is likely due to natural features of the Jihro River
      promoting sedimentation before reaching coastal sites. We provide an important
      baseline for Solomon Island inshore systems, whilst demonstrating the importance
      of continuous monitoring to capture episodic high turbidity events. 

PMID- 25752530
TI  - Genetic mechanisms of abiotic stress tolerance that translate to crop yield
      stability.
AB  - Crop yield reduction as a consequence of increasingly severe climatic events
      threatens global food security. Genetic loci that ensure productivity in
      challenging environments exist within the germplasm of crops, their wild
      relatives and species that are adapted to extreme environments. Selective
      breeding for the combination of beneficial loci in germplasm has improved yields
      in diverse environments throughout the history of agriculture. An effective new
      paradigm is the targeted identification of specific genetic determinants of
      stress adaptation that have evolved in nature and their precise introgression
      into elite varieties. These loci are often associated with distinct regulation or
      function, duplication and/or neofunctionalization of genes that maintain plant
      homeostasis. 

PMID- 25752533
TI  - Potential oil spill risk from shipping and the implications for management in the
      Caribbean Sea.
AB  - The semi enclosed Caribbean Sea is ranked as having one of the most intense
      maritime traffic in the world. These maritime activities have led to significant
      oil pollution. Simultaneously, this sea supports many critical habitats
      functioning as a Large Marine Ecosystem (LME). While the impacts of oil pollution
      are recognised, a number of management challenges remain. This study applies
      spatial modelling to identify critical areas potentially at risk from oil spills
      in the form of a potential oil spill risk (POSR) model. The model indicates that
      approximately 83% of the sea could be potentially impacted by oil spills due to
      shipping. The results from this study collectively support a management framework
      for minimising ship generated oil pollution in the Caribbean Sea. Among the
      recommended components are a common policy, surveillance and monitoring controls,
      standards, monitoring programmes, data collection and greater rates of convention
      ratifications. 

PMID- 25752534
TI  - Impact of harbour, industry and sewage on the phosphorus geochemistry of a
      subtropical estuary in Brazil.
AB  - The distribution of different forms of phosphorus in surface sediment from 17
      sites were investigated by SEDEX method. The sites were divided into three
      sectors: Santos Channel (SC - influenced by harbour, fertilizers plants and
      phosphogypsum mountains), Sao Vicente Channel (SVC- domestic waste) and Santos
      Bay (SB - sewage outfall). The average percentage of each P fraction of the
      surface sediments in this region followed the sequence P-Fe (38%)>P org (27%)>P
      exch (13%)>Detrital - P (12%)>Auth - P (10%). P total varied from 3.57 to 74.11
      MUmol g(-)(1) in both seasons. In SVC, P exch ranged from 13% to 27% and P org
      varied from 12% to 56%. These high percentages of P exch/P total (greater than
      20%) may be related to low oxygen resulting from oxygen consumed by intensive
      organic matter decomposition as well as the salty water that leads to cation and
      anion flocculation. Also, the possibility of an influence related to the
      industrial source of P exch is not ruled out. No significant seasonal differences
      were found among sites, except for sewage outfall, with changing in the grain
      size and hence, the P geochemistry. During the summer in the sewage outfall
      station, Porg represented 37% of P total, which decreased to 13% in the winter.
      These results suggest that high percentages of organic phosphorus cannot be
      attributed only to autochthonous and allochthonous organic matter, but also to
      detergents and/or domestic waste. In contrast, spatial differences among sectors
      were observed, with the highest values of each fraction associated with sites
      near industrial and domestic waste activities.

PMID- 25752535
TI  - Passive sampling reversed: coupling passive field sampling with passive lab
      dosing to assess the ecotoxicity of mixtures present in the marine environment.
AB  - This study presents a new approach in aquatic toxicity testing combining passive
      sampling and passive dosing. Polydimethylsiloxane sheets were used to sample
      contaminant mixtures in the marine environment. These sheets were subsequently
      transferred to ecotoxicological test medium in which the sampled contaminant
      mixtures were released through passive dosing. 4 out of 17 of these mixtures
      caused severe effects in a growth inhibition assay with a marine diatom. These
      effects could not be explained by the presence of compounds detected in the
      sampling area and were most likely attributable to unmeasured compounds absorbed
      to the passive samplers during field deployment. The findings of this study
      indicate that linking passive sampling in the field to passive dosing in
      laboratory ecotoxicity tests provides a practical and complimentary approach for
      assessing the toxicity of hydrophobic contaminant mixtures that mimics realistic
      environmental exposures. Limitations and opportunities for future improvements
      are presented. 

PMID- 25752536
TI  - Evidencing the natural and anthropogenic processes controlling trace metals
      dynamic in a highly stratified estuary: The Krka River estuary (Adriatic,
      Croatia).
AB  - Distributions of trace metals (TM), organic carbon, SPM and physico-chemical
      parameters were studied in the highly stratified Krka River estuary in
      winter/summer periods. The non-conservative behaviour of Zn, Cd, Pb and Cu in the
      brackish layer (plume), easily spotted due to very low inputs by the river, was
      mainly caused by their inputs from the pleasure boats, nautical marinas and
      harbour (e.g. release from antifouling paints). Contrarily, Ni and Co followed
      near-conservative behaviour. The extremely low SPM discharged by the river,
      resulted in a predominant dissolved fraction (>80%) of all TM, except Pb.
      Vertical scavenging, coupled with the long residence time, caused accumulation
      and progressive upstream increase of TM and SPM in the bottom seawater. Decrease
      of distribution coefficient (KD) in the brackish layer for winter period was
      ascribed to the change of SPM nature (terrestrial vs. biogenic), whereas a
      variable and increased biogenic component of SPM caused scattered KDs in summer. 

PMID- 25752537
TI  - Natural dispersion revisited.
AB  - This paper presents a new semi-empirical model for oil droplet size distributions
      generated by single breaking wave events. Empirical data was obtained from
      laboratory experiments with different crude oils at different stages of
      weathering. The paper starts with a review of the most commonly used model for
      natural dispersion, which is followed by a presentation of the laboratory study
      on oil droplet size distributions formed by breaking waves conducted by SINTEF on
      behalf of the NOAA/UNH Coastal Response Research Center. The next section
      presents the theoretical and empirical foundation for the new model. The model is
      based on dimensional analysis and contains two non-dimensional groups; the Weber
      and Reynolds number. The model was validated with data from a full scale
      experimental oil spill conducted in the Haltenbanken area offshore Norway in July
      1982, as described in the last section of the paper. 

PMID- 25752538
TI  - Electrospun PS/PAN fibers with improved mechanical property for removal of oil
      from water.
AB  - A mechanically robust and high-capacity oil sorbent is prepared by
      electrospinning a blend of polystyrene (PS) and polyacrylonitrile (PAN). The
      morphology, oil sorption capacity and mechanical property of the fibers formed in
      different compositions are investigated in detail. It is shown that the oil
      sorption capacity is a result of both the chemical composition and the specific
      surface area which related to diameter size. The addition of PAN as a component
      in fibrous sorbents can significantly improve the mechanical properties of PS
      fibers. Moreover, the oil sorption capacity increases with decreasing fiber
      diameter. The results also show that the maximum sorption capacities of the
      PS/PAN sorbent for pump oil, peanut oil, diesel, and gasoline were 194.85,
      131.70, 66.75, and 43.38 g g(-1), respectively. Additionally, the sorbent
      exhibits quick oil sorption speed as well as high buoyancy, which make it a
      promising candidate for use as an oil spill cleanup sorbent.

PMID- 25752540
TI  - Structural analysis of bacterial ABC transporter inhibition by an antibody
      fragment.
AB  - Bacterial ATP-binding cassette (ABC) importers play critical roles in nutrient
      acquisition and are potential antibacterial targets. However, structural bases
      for their inhibition are poorly defined. These pathways typically rely on
      substrate binding proteins (SBPs), which are essential for substrate recognition,
      delivery, and transporter function. We report the crystal structure of a
      Staphylococcus aureus SBP for Mn(II), termed MntC, in complex with FabC1, a
      potent antibody inhibitor of the MntABC pathway. This pathway is essential and
      highly expressed during S. aureus infection and facilitates the import of Mn(II),
      a critical cofactor for enzymes that detoxify reactive oxygen species (ROS).
      Structure-based functional studies indicate that FabC1 sterically blocks a
      structurally conserved surface of MntC, preventing its interaction with the MntB
      membrane importer and increasing wild-type S. aureus sensitivity to oxidative
      stress by more than 10-fold. The results define an SBP blocking mechanism as the
      basis for ABC importer inhibition by an engineered antibody fragment. 

PMID- 25752539
TI  - Physical activity and adiposity markers at older ages: accelerometer vs
      questionnaire data.
AB  - OBJECTIVE: Physical activity is critically important for successful aging, but
      its effect on adiposity markers at older ages is unclear as much of the evidence
      comes from self-reported data on physical activity. We assessed the associations
      of questionnaire-assessed and accelerometer-assessed physical activity with
      adiposity markers in older adults. DESIGN/SETTING/PARTICIPANTS: This was a cross
      sectional study on 3940 participants (age range 60-83 years) of the Whitehall II
      study who completed a 20-item physical activity questionnaire and wore a wrist
      mounted accelerometer for 9 days in 2012 and 2013. MEASUREMENTS: Total physical
      activity was estimated using metabolic equivalent hours/week for the
      questionnaire and mean acceleration for the accelerometer. Time spent in moderate
      and-vigorous physical activity (MVPA) was also assessed by questionnaire and
      accelerometer. Adiposity assessment included body mass index, waist
      circumference, and fat mass index. Fat mass index was calculated as fat
      mass/height2 (kg/m2), with fat mass estimated using bioimpedance. RESULTS:
      Greater total physical activity was associated with lower adiposity for all
      adiposity markers in a dose-response manner. In men, the strength of this
      association was 2.4 to 2.8 times stronger with the accelerometer than with
      questionnaire data. In women, it was 1.9 to 2.3 times stronger. For MVPA,
      questionnaire data in men suggested no further benefit for adiposity markers past
      1 hour/week of activity. This was not the case for accelerometer-assessed MVPA
      where, for example, compared with men undertaking <1 hour/week of accelerometer
      assessed MVPA, waist circumference was 3.06 (95% confidence interval 2.06-4.06)
      cm lower in those performing MVPA 1-2.5 hours/week, 4.69 (3.47-5.91) cm lower in
      those undertaking 2.5-4 hours/week, and 7.11 (5.93-8.29) cm lower in those
      performing >=4 hours/week. CONCLUSIONS: The association of physical activity with
      adiposity markers in older adults was stronger when physical activity was
      assessed by accelerometer compared with questionnaire, suggesting that physical
      activity might be more important for adiposity than previously estimated.

PMID- 25752541
TI  - Ankyrin repeats of ANKRA2 recognize a PxLPxL motif on the 3M syndrome protein
      CCDC8.
AB  - Peptide motifs are often used for protein-protein interactions. We have recently
      demonstrated that ankyrin repeats of ANKRA2 and the paralogous bare lymphocyte
      syndrome transcription factor RFXANK recognize PxLPxL/I motifs shared by megalin,
      three histone deacetylases, and RFX5. We show here that that CCDC8 is a major
      partner of ANKRA2 but not RFXANK in cells. The CCDC8 gene is mutated in 3M
      syndrome, a short-stature disorder with additional facial and skeletal
      abnormalities. Two other genes mutated in this syndrome encode CUL7 and OBSL1.
      While CUL7 is a ubiquitin ligase and OBSL1 associates with the cytoskeleton,
      little is known about CCDC8. Binding and structural analyses reveal that the
      ankyrin repeats of ANKRA2 recognize a PxLPxL motif at the C-terminal region of
      CCDC8. The N-terminal part interacts with OBSL1 to form a CUL7 ligase complex.
      These results link ANKRA2 unexpectedly to 3M syndrome and suggest novel
      regulatory mechanisms for histone deacetylases and RFX7. 

PMID- 25752542
TI  - Structures of C1q-like proteins reveal unique features among the C1q/TNF
      superfamily.
AB  - C1q-like (C1QL) -1, -2, and -3 proteins are encoded by homologous genes that are
      highly expressed in brain. C1QLs bind to brain-specific angiogenesis inhibitor 3
      (BAI3), an adhesion-type G-protein coupled receptor that may regulate dendritic
      morphology by organizing actin filaments. To begin to understand the function of
      C1QLs, we determined high-resolution crystal structures of the globular C1q
      domains of C1QL1, C1QL2, and C1QL3. Each structure is a trimer, with each
      protomer forming a jelly-roll fold consisting of 10 beta strands. Moreover, C1QL
      trimers may assemble into higher-order oligomers similar to adiponectin and
      contain four Ca(2+)-binding sites along the trimeric symmetry axis, as well as
      additional surface Ca(2+)-binding sites. Mutation of Ca(2+)-coordinating residues
      along the trimeric symmetry axis lowered the Ca(2+)-binding affinity and protein
      stability. Our results reveal unique structural features of C1QLs among C1q/TNF
      superfamily proteins that may be associated with their specific brain functions. 

PMID- 25752544
TI  - Rethinking trial eligibility in the NCD era.

PMID- 25752545
TI  - Bevacizumab and quality of life in advanced cervical cancer.

PMID- 25752543
TI  - Structural basis for VEGF-C binding to neuropilin-2 and sequestration by a
      soluble splice form.
AB  - Vascular endothelial growth factor C (VEGF-C) is a potent lymphangiogenic
      cytokine that signals via the coordinated action of two cell surface receptors,
      Neuropilin-2 (Nrp2) and VEGFR-3. Diseases associated with both loss and gain of
      VEGF-C function, lymphedema and cancer, respectively, motivate studies of VEGF
      C/Nrp2 binding and inhibition. Here, we demonstrate that VEGF-C binding to Nrp2
      is regulated by C-terminal proteolytic maturation. The structure of the VEGF-C C
      terminus in complex with the ligand binding domains of Nrp2 demonstrates that a
      cryptic Nrp2 binding motif is released upon proteolysis, allowing specific
      engagement with the b1 domain of Nrp2. Based on the identified structural
      requirements for Nrp2 binding to VEGF-C, we hypothesized that the endogenous
      secreted splice form of Nrp2, s9Nrp2, may function as a selective inhibitor of
      VEGF-C. We find that s9Nrp2 forms a stable dimer that potently inhibits VEGF
      C/Nrp2 binding and cellular signaling. These data provide critical insight into
      VEGF-C/Nrp2 binding and inhibition. 

PMID- 25752546
TI  - Trabectedin tactics: from sea squirts to sarcomas.

PMID- 25752547
TI  - Stereotactic radiosurgery alone for brain metastases.

PMID- 25752548
TI  - Japanese universal health care faces a crisis in cancer treatment.

PMID- 25752552
TI  - Japanese regulatory authority's perspective on biosimilars.

PMID- 25752553
TI  - Japanese regulatory authority's perspective on biosimilars - authors' reply.

PMID- 25752555
TI  - Adjuvant chemotherapy in locally advanced bladder cancer.

PMID- 25752554
TI  - Body-mass index, cancer, and implications for screening.

PMID- 25752556
TI  - The oncological package: a new source of concern in Poland's health system.

PMID- 25752557
TI  - Correction to Lancet Oncol 2015; 16: 181, 184.

PMID- 25752558
TI  - Correction to Lancet Oncol 2015; 16: 274.

PMID- 25752559
TI  - Correction to Lancet Oncol 2015; 16: 266.

PMID- 25752560
TI  - Correction to Lancet Oncol 2015; 16: 133.

PMID- 25752561
TI  - Correction to Lancet Oncol 2015; 16: 237.

PMID- 25752562
TI  - Radiation therapy in the locoregional treatment of triple-negative breast cancer.
AB  - This Review assesses the relevant data and controversies regarding the use of
      radiotherapy for, and locoregional management of, women with triple-negative
      breast cancer (TNBC). In view of the strong association between BRCA1 and TNBC,
      knowledge of baseline mutation status can be useful to guide locoregional
      treatment decisions. TNBC is not a contraindication for breast conservation
      therapy because data suggest increased locoregional recurrence risks (relative to
      luminal subtypes) with breast conservation therapy or mastectomy. Although a
      boost to the tumour bed should routinely be considered after whole breast
      radiation therapy, TNBC should not be the sole indication for post-mastectomy
      radiation, and accelerated delivery methods for TNBC should be offered on
      clinical trials. Preliminary data implying a relative radioresistance for TNBC do
      not imply radiation omission because radiation provides an absolute locoregional
      risk reduction. At present, the integration of subtypes in locoregional
      management decisions is still in its infancy. Until level 1 data supporting
      treatment decisions based on subtypes are available, standard locoregional
      management principles should be adhered to. 

PMID- 25752565
TI  - Morphogenetic fields of embryonic development in locoregional cancer spread.
AB  - The ontogenetic theory of locoregional cancer spread regards cancer as a clinical
      manifestation of the pathological reactivation and maintenance of the sequential
      developmental programmes that previously controlled the stepwise embryological
      morphogenesis of the tissue from which the cancer originated. In the state of
      morphostasis that characterises adult organisms, these programmes are silenced.
      During malignant progression, these programmes run in retrograde sequence, which
      leads to cancer infiltration of ever larger tissue areas. However, because the
      reactivated morphogenetic programmes need topologically defined tissue domains-
      morphogenetic fields--to provide positional information for their interpretation,
      local tumour propagation is confined to permissive compartments (topographically
      defined tissue domains where malignant cells can survive, migrate, and
      proliferate), which are determined by the state of malignant progression. The
      tissue at risk of local tumour spread, the cancer field, is the mature tissue
      derived from the corresponding morphogenetic field in the embryo, which is
      labelled with the respective positional information. The theory can be tested
      morphologically and clinically for all tumours. Verification of this theory would
      offer substantial potential to improve prognostic assessment and surgical
      treatment. Identification of the complementary positional information for tumour
      cells in different ontogenetic stages, and their associated cancer fields, could
      be a molecular research strategy to further test the theory.

PMID- 25752564
TI  - Optimisation of the continuum of supportive and palliative care for patients with
      breast cancer in low-income and middle-income countries: executive summary of the
      Breast Health Global Initiative, 2014.
AB  - Supportive care and palliative care are now recognised as critical components of
      global cancer control programmes. Many aspects of supportive and palliative care
      services are already available in some low-income and middle-income countries.
      Full integration of supportive and palliative care into breast cancer programmes
      requires a systematic, resource-stratified approach. The Breast Health Global
      Initiative convened three expert panels to develop resource allocation
      recommendations for supportive and palliative care programmes in low-income and
      middle-income countries. Each panel focused on a specific phase of breast cancer
      care: during treatment, after treatment with curative intent (survivorship), and
      after diagnosis with metastatic disease. The panel consensus statements were
      published in October, 2013. This Executive Summary combines the three panels'
      recommendations into a single comprehensive document covering breast cancer care
      from diagnosis through curative treatment into survivorship, and metastatic
      disease and end-of-life care. The recommendations cover physical symptom
      management, pain management, monitoring and documentation, psychosocial and
      spiritual aspects of care, health professional education, and patient, family,
      and caregiver education. 

PMID- 25752566
TI  - Genetic characterization of Moniezia species in Senegal and Ethiopia.
AB  - Genetic diversity of Moniezia spp. from domestic ruminants in Senegal and
      Ethiopia was investigated based on the nucleotide sequences of mitochondrial
      cytochrome c oxidase subunit 1 (cox1) and nuclear small subunit ribosomal RNA
      gene (SSU rDNA). A total of 64 adult tapeworms were collected from sheep, goat
      and cattle, and the tapeworms from cattle were all morphologically identified as
      Moniezia benedeni. On the other hand, the tapeworms obtained from sheep and goat
      were identified as Moniezia expansa or could not be identified because of the
      lack of diagnostic morphologic character, i.e. interproglottidal glands (IPGs).
      Phylogenetic analysis based on cox1 gene sequences revealed that the worms from
      sheep/goat and cattle formed distinct clades, and three mitochondrial lineages
      were confirmed within the sheep/goat tapeworms. The maximum pairwise divergences
      among the three mitochondrial linages were about 3% in cox1 and 0.1% in SSU rDNA,
      while that between the worms from sheep/goat and cattle reached 13% in cox1 and
      2.7% in SSU rDNA. All of the three mitochondrial lineages contained tapeworms
      morphologically identified as M. expansa, and the tapeworms without IPGs were
      confirmed in one of the three lineages, indicating the tapeworms without IPGs
      were also M. expansa. 

PMID- 25752568
TI  - Near-fatal outcome from absence of information about exercise-associated
      hyponatremia in a wilderness medicine field guidebook.

PMID- 25752563
TI  - Recommendations for cardiomyopathy surveillance for survivors of childhood
      cancer: a report from the International Late Effects of Childhood Cancer
      Guideline Harmonization Group.
AB  - Survivors of childhood cancer treated with anthracycline chemotherapy or chest
      radiation are at an increased risk of developing congestive heart failure. In
      this population, congestive heart failure is well recognised as a progressive
      disorder, with a variable period of asymptomatic cardiomyopathy that precedes
      signs and symptoms. As a result, several clinical practice guidelines have been
      developed independently to help with detection and treatment of asymptomatic
      cardiomyopathy. These guidelines differ with regards to definitions of at-risk
      populations, surveillance modality and frequency, and recommendations for
      interventions. Differences between these guidelines could hinder the effective
      implementation of these recommendations. We report on the results of an
      international collaboration to harmonise existing cardiomyopathy surveillance
      recommendations using an evidence-based approach that relied on standardised
      definitions for outcomes of interest and transparent presentation of the quality
      of the evidence. The resultant recommendations were graded according to the
      quality of the evidence and the potential benefit gained from early detection and
      intervention. 

PMID- 25752567
TI  - Killing of Streptococcus pneumoniae by azithromycin, clarithromycin,
      erythromycin, telithromycin and gemifloxacin using drug minimum inhibitory
      concentrations and mutant prevention concentrations.
AB  - Streptococcus pneumoniae continues to be a significant respiratory pathogen, and
      increasing antimicrobial resistance compromises the use of beta-lactam and
      macrolide antibiotics. Bacterial eradication impacts clinical outcome, and
      bacterial loads at the site of infection may fluctuate. Killing of two macrolide-
      and quinolone-susceptible clinical S. pneumoniae isolates by azithromycin,
      clarithromycin, erythromycin, telithromycin and gemifloxacin against varying
      bacterial densities was determined using the measured minimum inhibitory
      concentration (MIC) and mutant prevention concentration (MPC). For kill
      experiments, 10(6)-10(9) CFU/mL were exposed to the drug and were sampled at 0,
      0.5, 1, 2, 3, 4, 6, 12 and 24 h following drug exposure. The log(10) reduction
      and percent reduction (kill) of viable cells was recorded. MICs and MPCs (mg/L)
      for azithromycin, clarithromycin, erythromycin, telithromycin and gemifloxacin
      were 0.063-0.125/0.5-1, 0.031-0.063/0.25-0.5, 0.063/0.25-0.5, 0.008/0.016 and
      0.031/0.25, respectively. Killing 10(6)-10(9) CFU/mL of bacteria by the drug MIC
      yielded incomplete killing, however log10 reductions occurred by 12 h and 24 h
      for all drugs. Exposure of 10(6)-10(9) CFU/mL to MPC drug concentrations resulted
      in the following log(10) reduction by 6h of drug exposure: azithromycin, 1.3-3.9;
      clarithromycin, 1.9-5.8; erythromycin, 0.8-4.7; telithromycin, 0.3-1.7; and
      gemifloxacin, 1.8-4.2. Bacterial loads at the site of infection may range from
      10(6) to 10(9), and kill experiments utilising a higher bacterial inoculum
      provided a more accurate measure of antibiotic performance in high biomass
      situations. Killing was slower with telithromycin. Kill was greater and fastest
      with MPC versus MIC drug concentrations.

PMID- 25752569
TI  - Characterization of neutron fields from bare and heavy water moderated (252)Cf
      spontaneous fission source using Bonner Sphere Spectrometer.
AB  - In this work a calibrated Bonner Sphere Spectrometer (BSS), together with ISO
      shadow cones, was used to quantify the total and scattered components of bare and
      heavy water moderated (252)Cf neutron fields. All measurements were performed
      with a BSS that was calibrated at the National Physical Laboratory (NPL),
      Teddington, UK, which is a global primary standard laboratory and world-leading
      facility for neutron metrology and neutron instruments calibration. The fields
      were characterized for source-spectrometer distances of 80, 100, 150 and 200cm;
      and at heights of 103 and 200cm from the facility floor. As expected, the
      scattered contribution was greatest at the farthest distance from the source and
      closer to the floor. Hence, at a distance of 200cm and a height of 103cm, the
      scatter added to the direct field up to 162% of the total neutron fluence and up
      to 61% of the ambient dose equivalent, while at the same distance and height of
      200cm above the floor, these values were up to 146% and 52%, respectively. In the
      case of heavy water moderated (252)Cf neutron fields, a shadow cone subtraction
      technique could not be implemented, however Monte Carlo simulations were utilized
      in order to differentiate between the direct and scatter components of the
      neutron fields. In this case, at a source-detector distance of 200cm and a height
      of 103cm, the scatter added to the direct field up to 148% of the total neutron
      fluence and up to 45% of the ambient dose equivalent, while at the same distance
      and a height of 200cm above the floor, these values were up to 134% and 42%,
      respectively. 

PMID- 25752570
TI  - Automated radiosynthesis of [(18)F]ciprofloxacin.
AB  - We transferred the previously published manual synthesis of [(18)F]ciprofloxacin
      (decay-corrected RCY: 5.5+/-1.0%) to an automated synthesis module (TRACERlab(TM)
      FXFDG, GE Healthcare) and observed a strong decrease in RCY (0.4+/-0.4%). When
      replacing the standard 15-mL glassy carbon reactor of the synthesis module with a
      3-mL V-shaped borosilicate glass reactor a considerable improvement in RCY was
      observed. [(18)F]Ciprofloxacin was obtained in a RCY of 2.7+/-1.4% (n=23) with a
      specific activity at EOS of 1.4+/-0.5GBq/umol in a synthesis time of 160min. 

PMID- 25752571
TI  - Symptom management of gynecologic cancers: refocusing on the forest.

PMID- 25752572
TI  - Central nervous system metastasis in gynecologic cancer: symptom management,
      prognosis and palliative management strategies.
AB  - INTRODUCTION: CNS metastasis (CNSmet) with gynecologic malignancy (GM) is
      associated with poor prognosis and symptom burden. Two prognostic indices, the
      recursive partitioning analysis (RPA) and graded prognostic assessment (GPA),
      used in other solid tumors to guide intervention options were evaluated among GM
      patients. METHODS: Retrospective chart review was performed to identify patients
      with primary GM diagnosed with CNSmet from 2005-2014. RPA and GPA were applied
      and evaluated for goodness of fit. Long-term survivors (LTS) were those with
      survival time from CNSmet >=9 months. RESULTS: 35 patients were identified with
      median age of 62 years (range, 41-78). The majority had ovarian cancer (54%).
      Median survival was 4.5 months (0.1-25.9), and median time from initial diagnosis
      was 2.6 years (0-19.6). Presenting symptoms varied but headache (57%) and altered
      mental status (23%) were most common. 37% had a solitary CNS lesion, 31% had 2-8,
      and 31% >8. 57% were treated with WBRT, 14% with stereotactic radiosurgery (SRS),
      and 20% with combinations of treatments, and 2 elected for hospice. 27% (9/33) of
      the patients were LTS. The GPA was not significantly associated with patient
      outcome (p=0.46). The RPA predicted time to death (p=.0010). CONCLUSION:
      Prognostic indices used to guide therapeutic interventions perform poorly in GM.
      Detection and aggressive symptom management are critical in maintaining QOL.
      Multidisciplinary consultation is critical to optimize outcomes and symptom
      control.

PMID- 25752573
TI  - K29-selective ubiquitin binding domain reveals structural basis of specificity
      and heterotypic nature of k29 polyubiquitin.
AB  - Polyubiquitin chains regulate diverse cellular processes through the ability of
      ubiquitin to form chains of eight different linkage types. Although detected in
      yeast and mammals, little is known about K29-linked polyubiquitin. Here we report
      the generation of K29 chains in vitro using a ubiquitin chain-editing complex
      consisting of the HECT E3 ligase UBE3C and the deubiquitinase vOTU. We determined
      the crystal structure of K29-linked diubiquitin, which adopts an extended
      conformation with the hydrophobic patches on both ubiquitin moieties exposed and
      available for binding. Indeed, the crystal structure of the NZF1 domain of TRABID
      in complex with K29 chains reveals a binding mode that involves the hydrophobic
      patch on only one of the ubiquitin moieties and exploits the flexibility of K29
      chains to achieve linkage selective binding. Further, we establish methods to
      study K29-linked polyubiquitin and find that K29 linkages exist in cells within
      mixed or branched chains containing other linkages. 

PMID- 25752574
TI  - TNFalpha signaling exposes latent estrogen receptor binding sites to alter the
      breast cancer cell transcriptome.
AB  - The interplay between mitogenic and proinflammatory signaling pathways plays key
      roles in determining the phenotypes and clinical outcomes of breast cancers.
      Using GRO-seq in MCF-7 cells, we defined the immediate transcriptional effects of
      crosstalk between estradiol (E2) and TNFalpha, identifying a large set of target
      genes whose expression is rapidly altered with combined E2 + TNFalpha treatment,
      but not with either agent alone. The pleiotropic effects on gene transcription in
      response to E2 + TNFalpha are orchestrated by extensive remodeling of the ERalpha
      enhancer landscape in an NF-kappaB- and FoxA1-dependent manner. In addition,
      expression of the de novo and synergistically regulated genes is strongly
      associated with clinical outcomes in breast cancers. Together, our genomic and
      molecular analyses indicate that TNFalpha signaling, acting in pathways
      culminating in the redistribution of NF-kappaB and FoxA1 binding sites across the
      genome, creates latent ERalpha binding sites that underlie altered patterns of
      gene expression and clinically relevant cellular responses. 

PMID- 25752575
TI  - Phosphoproteomics reveals distinct modes of Mec1/ATR signaling during DNA
      replication.
AB  - The Mec1/Tel1 kinases (human ATR/ATM) play numerous roles in the DNA replication
      stress response. Despite the multi-functionality of these kinases, studies of
      their in vivo action have mostly relied on a few well-established substrates.
      Here we employed a combined genetic-phosphoproteomic approach to monitor
      Mec1/Tel1 signaling in a systematic, unbiased, and quantitative manner.
      Unexpectedly, we find that Mec1 is highly active during normal DNA replication,
      at levels comparable or higher than Mec1's activation state induced by
      replication stress. This "replication-correlated" mode of Mec1 action requires
      the 9-1-1 clamp and the Dna2 lagging-strand factor and is distinguishable from
      Mec1's action in activating the downstream kinase Rad53. We propose that Mec1/ATR
      performs key functions during ongoing DNA synthesis that are distinct from their
      canonical checkpoint role during replication stress. 

PMID- 25752576
TI  - Viral pseudo-enzymes activate RIG-I via deamidation to evade cytokine production.
AB  - RIG-I is a pattern recognition receptor that senses viral RNA and is crucial for
      host innate immune defense. Here, we describe a mechanism of RIG-I activation
      through amidotransferase-mediated deamidation. We show that viral homologs of
      phosphoribosylformylglycinamidine synthetase (PFAS), although lacking intrinsic
      enzyme activity, recruit cellular PFAS to deamidate and activate RIG-I.
      Accordingly, depletion and biochemical inhibition of PFAS impair RIG-I
      deamidation and concomitant activation. Purified PFAS and viral homolog thereof
      deamidate RIG-I in vitro. Ultimately, herpesvirus hijacks activated RIG-I to
      avoid antiviral cytokine production; loss of RIG-I or inhibition of RIG-I
      deamidation results in elevated cytokine production. Together, these findings
      demonstrate a surprising mechanism of RIG-I activation that is mediated by an
      enzyme. 

PMID- 25752577
TI  - Assembly and specific recognition of k29- and k33-linked polyubiquitin.
AB  - Protein ubiquitination regulates many cellular processes via attachment of
      structurally and functionally distinct ubiquitin (Ub) chains. Several atypical
      chain types have remained poorly characterized because the enzymes mediating
      their assembly and receptors with specific binding properties have been elusive.
      We found that the human HECT E3 ligases UBE3C and AREL1 assemble K48/K29- and
      K11/K33-linked Ub chains, respectively, and can be used in combination with DUBs
      to generate K29- and K33-linked chains for biochemical and structural analyses.
      Solution studies indicate that both chains adopt open and dynamic conformations.
      We further show that the N-terminal Npl4-like zinc finger (NZF1) domain of the
      K29/K33-specific deubiquitinase TRABID specifically binds K29/K33-linked diUb,
      and a crystal structure of this complex explains TRABID specificity and suggests
      a model for chain binding by TRABID. Our work uncovers linkage-specific
      components in the Ub system for atypical K29- and K33-linked Ub chains, providing
      tools to further understand these unstudied posttranslational modifications. 

PMID- 25752578
TI  - Two distinct DNA binding modes guide dual roles of a CRISPR-Cas protein complex.
AB  - Small RNA-guided protein complexes play an essential role in CRISPR-mediated
      immunity in prokaryotes. While these complexes initiate interference by flagging
      cognate invader DNA for destruction, recent evidence has implicated their
      involvement in new CRISPR memory formation, called priming, against mutated
      invader sequences. The mechanism by which the target recognition complex mediates
      these disparate responses-interference and priming-remains poorly understood.
      Using single-molecule FRET, we visualize how bona fide and mutated targets are
      differentially probed by E. coli Cascade. We observe that the recognition of bona
      fide targets is an ordered process that is tightly controlled for high fidelity.
      Mutated targets are recognized with low fidelity, which is featured by short
      lived and PAM- and seed-independent binding by any segment of the crRNA. These
      dual roles of Cascade in immunity with distinct fidelities underpin CRISPR-Cas
      robustness, allowing for efficient degradation of bona fide targets and priming
      of mutated DNA targets. 

PMID- 25752579
TI  - Versatile antifouling polyethersulfone filtration membranes modified via surface
      grafting of zwitterionic polymers from a reactive amphiphilic copolymer additive.
AB  - Here we describe the development of versatile antifouling polyethersulfone (PES)
      filtration membranes modified via surface grafting of zwitterionic polymers from
      a reactive amphiphilic copolymer additive. Amphiphilic polyethersulfone-block
      poly(2-hydroxyethyl methacrylate) (PES-b-PHEMA) was beforehand designed and used
      as the blending additive of PES membranes prepared by phase inversion technique.
      The surface enriched PHEMA blocks on membrane surface acted as an anchor to
      immobilize the initiating site. Poly(sulfobetaine methacrylate) (PSBMA) were
      subsequently grafted onto the PES blend membranes by surface-initiated atom
      transfer radical polymerization (SI-ATRP). The analysis of surface chemistry
      confirmed the successful grafting of zwitterionic PSBMA brushes on PES membrane
      surface. The resulted PES-g-PSBMA membranes were capable of separating proteins
      from protein solution and oil from oil/water emulsion efficiently. Furthermore,
      the modified membranes showed high hydrophilicity and strongly antifouling
      properties due to the incorporation of well-defined PSBMA layer. In addition, the
      PES-g-PSBMA membranes exhibited excellent blood compatibility and durability
      during the washing process. The developed antifouling PES membranes are versatile
      and can find their applications in protein filtration, blood purification and
      oil/water separation, etc. 

PMID- 25752580
TI  - Improvement of the interfacial compatibility between cellulose and poly(L
      lactide) films by plasma-induced grafting of L-lactide: the evaluation of the
      adhesive properties using a peel test.
AB  - HYPOTHESIS: The interfacial compatibility between hydrophilic cellulose and
      hydrophobic poly(L-lactide) film surfaces is dependent on the interactions and
      interlocking of the macromolecular chains of the uppermost layers of both
      polymers. Grafting or coating the cellulose surface with molecular structures
      similar to the lactide monomer or oligomer is expected to improve the
      compatibility. Therefore, it should be possible to enhance the adhesive
      properties. EXPERIMENTS: Cellulose films were oxygen plasma treated and immersed
      in a L-lactide solution. The grafting was performed under various conditions
      (power, pressure, time). The treated cellulose and poly(L-lactide) films were hot
      pressed, and the resulting bi-layer laminates were subjected to a peel test.
      Comparative experiments were performed with the bi-layer laminates prepared from
      the cellulose films coated with poly(L-lactide-graft-vinyl alcohol) copolymers.
      FINDINGS: X-ray photoelectron spectroscopy, infra-red analyses and wettability
      measurements revealed that chains bearing ester groups similar to that of lactide
      were covalently grafted onto the cellulose. The possible grafting mechanism that
      was initiated by the ionic species from the surface is discussed. As a result,
      the peel strength to separate the cellulose and the poly(L-lactide) films
      increased significantly. A comparison with data in the literature highlights the
      formation of entanglements inside the interfacial zone showing the efficiency of
      the plasma treatment.

PMID- 25752581
TI  - Differentiating multiple-system atrophy from Parkinson's disease.
AB  - The purpose of this review is to illustrate the differentiating features of
      multiple-system atrophy from Parkinson's disease at MRI. The various MRI
      sequences helpful in the differentiation will be discussed, including newer
      methods, such as diffusion tensor imaging, MR spectroscopy, and nuclear imaging. 

PMID- 25752582
TI  - Perinatal management of neonatal alloimmune thrombocytopenia associated with anti
      group A antibody.
AB  - OBJECTIVE: To prevent neonatal alloimmune thrombocytopenia due to anti-group A
      antibody perinatal management was performed. BACKGROUND: We previously reported a
      case of severe intracranial haemorrhage associated with neonatal alloimmune
      thrombocytopenia due to anti-group A isoantibody. MATERIAL/METHODS: A 40-year-old
      Japanese woman, gravida 4 para 1, was pregnant with her second baby. The previous
      sibling developed severe thrombocytopenia and died 10 days after birth due to
      intracranial haemorrhage. He was diagnosed with neonatal alloimmune
      thrombocytopenia; the causative antibody was found to be the anti-group A
      antibody. Prednisone was started at 7 weeks' gestational age. Intravenous
      immunoglobulin 1 g kg(-1)  week(-1) was started at 29 weeks' gestational age and
      continued to delivery. Serological studies and genotyping were performed.
      RESULTS: The second boy was delivered at 33 weeks' gestational age by caesarean
      section. He was discharged without intracranial haemorrhage or thrombocytopenia.
      The anti-group A antibody titre in the maternal serum was 2048-4096 (normal
      range: 4-64). The anti-group A antibody titre in the newborn's serum was 4. Cross
      matching between the maternal serum and the paternal platelets was positive.
      CONCLUSION: Owing to the history of neonatal alloimmune thrombocytopenia causing
      intracranial haemorrhage and death of the previous sibling, strict follow-up of
      the subsequent pregnancy was conducted.

PMID- 25752583
TI  - School performance and oral health conditions: analysis of the impact mediated by
      socio-economic factors.
AB  - BACKGROUND: Oral problems can cause strong impact on functional, emotional, and
      social aspects of children and adolescents, as well as changes in school
      performance. AIM: To evaluate the associations of subjective perceptions of
      parents, socio-economic factors, and oral clinical conditions of children with
      their school performance. DESIGN: A case-control design was used with a sample of
      1411 schoolchildren aged 8-10 years from city of Piracicaba, Sao Paulo, Brazil.
      Clinical conditions were evaluated using the DMFT and dmft indexes. Socio
      economic data were obtained using a questionnaire sent to schoolchildren's
      parents. School performance was evaluated by the final scores of each schoolchild
      at the end of the 2011 school year. RESULTS: According to the final logistic
      regression model, the schoolchildren who had carious lesions and underwent
      curative dental treatment at the beginning of the academic year presented 1.51
      more chance of having low performance compared with schoolchildren who had no
      caries lesions. In addition, socio-economic and demographic variables were
      associated with a greater chance of poor school performance. CONCLUSION: Socio
      economic factors and presence of caries lesions, even if treated, were risk
      indicators for poor school performance.

PMID- 25752584
TI  - Effect of turning frequency and season on composting materials from swine high
      rise facilities.
AB  - Composting swine slurries has several advantages, liquid slurries are converted
      to solids at lower moisture, the total volume and weight of material is reduced
      and the stabilized product is more easily transported off-site. Despite this,
      swine waste is generally stored, treated and applied in its liquid form. High
      rise finishing facilities (HRFF) permit liquid slurries to be converted to solids
      which are partially decomposed underneath the HRFF and then finished in compost
      windrows. The purpose of this study was to evaluate the effect of turning
      frequency and ambient weather conditions on biological, physical and chemical
      properties of composted slurry-woodchip mixtures from HRFF. Compost trials were
      conducted in either fall (FT) or spring (ST) and piles were turned once or three
      times per week or upon compost temperature reaching 65 degrees C. Physical,
      chemical and microbiological characteristics were measured over the course of 112
      (FT) or 143 (ST) days of composting. Total carbon, total nitrogen (N) and
      inorganic N decreased in all piles. Ammonium decreased while nitrate increased in
      all piles (including unturned), but total N losses were greatest in piles turned
      more frequently during the ST. Microbial populations of nitrifiers were dominated
      by ammonia-oxidizing archaea (3.0*10(3)-4.2*10(6)cellsg(-1) compost) but ammonia
      oxidizing bacteria (below detection to 6.0*10(5)cellsg(-1) compost) varied in
      response to turning and compost temperature; denitrifiers were present in high
      concentrations throughout the process. Swine HRFF materials composted well in
      windrows regardless of turning frequency and despite significant differences in
      starting materials and low initial C/N. Volume reduction, low moisture and low
      readily degradable organic matter suggest that the finished compost would have
      lower transportation costs and should provide value as a soil conditioner. 

PMID- 25752586
TI  - Confirming the structure of negative beliefs about psychosis and bipolar
      disorder: A confirmatory factor analysis study of the Personal Beliefs about
      Experience Questionnaire and Personal Beliefs about Illness Questionnaire.
AB  - OBJECTIVES: Negative beliefs about psychosis and other mental health difficulties
      may contribute to depression and distress in individuals with these experiences.
      The Personal Beliefs about Experience Questionnaire (PBEQ) and Personal Beliefs
      about Illness Questionnaire (PBIllQ) are two widely used measures of these
      beliefs. It is currently uncertain how the items on these measures map onto
      different underlying factors. This study therefore aimed to test the factor
      structure of these two measures. METHODS: Confirmatory factor analysis (CFA) was
      used to test three alternative, pre-specified, factor structures for the PBIllQ
      and PBEQ in a sample of individuals diagnosed with bipolar disorder (n = 202) and
      a sample of individuals with experien-ces of psychosis (n = 362). Associations
      with depressive symptoms were also examined. RESULT: A three-factor structure was
      supported for both measures, which included Negative Expectations/Appraisals
      (NEA), Internal Shame/Defectiveness (ISD) and External Shame (ES) factors. The
      NEA and ISD subscales also had consistent independent associations with
      depressive symptoms. CONCLUSIONS: The results suggest that the PBIllQ and PBEQ
      may capture three distinct sets of negative beliefs in individuals with psychosis
      or bipolar disorder and that these beliefs may have important consequences for
      subsequent difficulties in these populations such as depression. Both measures
      may be helpful in supporting assessment and formulation in clinical practice and
      in evaluating belief change in intervention trials. However, when used in these
      settings, the three subscales identified in this study may be the most valid way
      of calculating scores on these measures. PRACTITIONER POINTS: Negative personal
      beliefs about the causes, meaning and consequences of psychosis and bipolar
      disorder are associated with greater distress and depression. Two related
      measures, the PBIllQ and PBEQ, have been developed to assess these beliefs. Our
      analyses suggest that scores on these questionnaires are best broken down into
      three subscales which capture perceptions of internal shame or defectiveness,
      general negative appraisals and perceptions of external shame. These subscales
      may capture key underlying sets of negative beliefs within individuals with
      psychosis or bipolar disorder, which in turn impact upon well-being, such as
      being associated with greater depression. These subscales can be used to aid
      assessment and formulation within clinical practice but may also provide a
      valuable means of assessing changes in negative beliefs following interventions.

PMID- 25752585
TI  - Memory integration in amnesia: prior knowledge supports verbal short-term memory.
AB  - Short-term memory (STM) and long-term memory (LTM) have traditionally been
      considered cognitively distinct. However, it is known that STM can improve when
      to-be-remembered information appears in contexts that make contact with prior
      knowledge, suggesting a more interactive relationship between STM and LTM. The
      current study investigated whether the ability to leverage LTM in support of STM
      critically depends on the integrity of the hippocampus. Specifically, we
      investigated whether the hippocampus differentially supports between-domain
      versus within-domain STM-LTM integration given prior evidence that the
      representational domain of the elements being integrated in memory is a critical
      determinant of whether memory performance depends on the hippocampus. In
      Experiment 1, we investigated hippocampal contributions to within-domain STM-LTM
      integration by testing whether immediate verbal recall of words improves in MTL
      amnesic patients when words are presented in familiar verbal contexts (meaningful
      sentences) compared to unfamiliar verbal contexts (random word lists). Patients
      demonstrated a robust sentence superiority effect, whereby verbal STM performance
      improved in familiar compared to unfamiliar verbal contexts, and the magnitude of
      this effect did not differ from that in controls. In Experiment 2, we
      investigated hippocampal contributions to between-domain STM-LTM integration by
      testing whether immediate verbal recall of digits improves in MTL amnesic
      patients when digits are presented in a familiar visuospatial context (a typical
      keypad layout) compared to an unfamiliar visuospatial context (a random keypad
      layout). Immediate verbal recall improved in both patients and controls when
      digits were presented in the familiar compared to the unfamiliar keypad array,
      indicating a preserved ability to integrate activated verbal information with
      stored visuospatial knowledge. Together, these results demonstrate that immediate
      verbal recall in amnesia can benefit from two distinct types of semantic support,
      verbal and visuospatial, and that the hippocampus is not critical for leveraging
      stored semantic knowledge to improve memory performance. 

PMID- 25752587
TI  - Ethnobotanical study of plants used against malaria in Selingue subdistrict,
      Mali.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Plants have contributed to food security and
      disease treatments to rural populations in sub Saharan Africa for many centuries.
      These plants occupy a significant place in the treatment of diseases, such as
      malaria. In Mali, malaria is the leading cause of medical consultation and death.
      This infection is particularly dangerous for pregnant women and children under 5
      years. The general aim of this research was to collect data on the knowledge of
      traditional health practitioners on malaria in the Selingue area; particularly to
      document how traditional healers conceptualize and diagnose malarial disease and
      to collect and identify medicinal plants or other substances used for their
      health and well-being. MATERIALS AND METHODS: An ethnobotanical survey was
      conducted on simple and complicated malaria in six villages in Selingue
      subdistrict in a period of 2 months. The ethnobotanical data was collected by
      means of semi-structured interviews and questionnaires. In total 50 traditional
      healers were interviewed. RESULTS: Two concepts of malaria (simple and
      complicated malaria) were cited and 97 plants used to treat malaria were
      identified. Decoctions and bathing (whole body) proved to be the most commonly
      used mode of application. Food attitudes and mosquitoes are perceived to be the
      most important causes of the disease. Trichilia emetica, Mitragyna inermis,
      Sarcocephalus latifolius, Cassia sieberiana, Cochlospermum tinctorium, Anogeissus
      leiocarpa, Guiera senegalensis and Entada africana were quoted as the most used
      in the treatment of malaria. CONCLUSION: Knowledge about malaria and traditional
      treatment practices exist in Selingue subdistrict. Herbal remedies are commonly
      used by people for the treatment of malaria because they are believed to be cost
      effective and more accessible. Many of the plant species used for the treatment
      of malaria have not been well documented as well as their phytochemical and
      antimalarial activity.

PMID- 25752589
TI  - Review article: Emergency department models of care in the context of care
      quality and cost: a systematic review.
AB  - To identify current ED models of care and their impact on care quality, care
      effectiveness, and cost. A systematic search of key health databases (Medline,
      CINAHL, Cochrane, EMbase) was conducted to identify literature on ED models of
      care. Additionally, a focused review of the contents of 11 international and
      national emergency medicine, nursing and health economic journals (published
      between 2010 and 2013) was undertaken with snowball identification of references
      of the most recent and relevant papers. Articles published between 1998 and 2013
      in the English language were included for initial review by three of the authors.
      Studies in underdeveloped countries and not addressing the objectives of the
      present study were excluded. Relevant details were extracted from the retrieved
      literature, and analysed for relevance and impact. The literature was synthesised
      around the study's main themes. Models described within the literature mainly
      focused on addressing issues at the input, throughput or output stages of ED care
      delivery. Models often varied to account for site specific characteristics (e.g.
      onsite inpatient units) or to suit staffing profiles (e.g. extended scope
      physiotherapist), ED geographical location (e.g. metropolitan or rural site), and
      patient demographic profile (e.g. paediatrics, older persons, ethnicity). Only a
      few studies conducted cost-effectiveness analysis of service models. Although
      various models of delivering emergency healthcare exist, further research is
      required in order to make accurate and reliable assessments of their safety,
      clinical effectiveness and cost-effectiveness. 

PMID- 25752588
TI  - alpha-Galactosylceramide suppresses murine eosinophil production through
      interferon-gamma-dependent induction of NO synthase and CD95.
AB  - BACKGROUND AND PURPOSE: alpha-Galactosylceramide (alpha-GalCer), a pleiotropic
      immunomodulator with therapeutic potential in neoplastic, autoimmune and allergic
      diseases, activates invariant natural killer T-cells throughCD1-restricted
      receptors for alpha-GalCer on antigen-presenting cells, inducing cytokine
      secretion. However the haemopoietic effects of alpha-GalCer remain little
      explored. EXPERIMENTAL APPROACH: alpha-GalCer-induced modulation of eosinophil
      production in IL-5-stimulated bone marrow cultures was examined in wild-type
      (BALB/c, C57BL/6) mice and their mutants lacking CD1, inducible NOS (iNOS), CD95
      and IFN-gamma, along with the effects of lymphocytes; IFN-gamma; caspase and iNOS
      inhibitors; non-steroidal anti-inflammatory drugs (NSAIDs) and LTD4 ; and
      dexamethasone. KEY RESULTS: alpha-GalCer (10(-6) -10(-8) M) suppressed IL-5
      stimulated eosinopoiesis by inducing apoptosis. alpha-GalCer pretreatment in vivo
      (100 MUg.kg(-1) , i.v.) suppressed colony formation by GM-CSF-stimulated bone
      marrow progenitors in semi-solid cultures. alpha-GalCer and dexamethasone
      synergistically promoted eosinophil maturation. Suppression of eosinophil
      production by alpha-GalCer was prevented by aminoguanidine and was undetectable
      in bone marrow lacking iNOS, CD95, CD28; or CD1d. Separation on Percoll gradients
      and depletion of CD3+ cells made bone marrow precursors unresponsive to alpha
      GalCer. Responsiveness was restored with splenic lymphocytes. Experiments with
      (i) IFN-gamma-deficient bone marrow, alone or co-cultured with spleen T-cells
      from wild-type, but not from CD1d-deficient, donors; (ii) IFN-gamma
      neutralization; and (iii) recombinant IFN-gamma, showed that these effects of
      alpha-GalCer were mediated by IFN-gamma. Effects of alpha-GalCer on eosinophil
      production were blocked by LTD4 and NSAIDs. CONCLUSIONS AND IMPLICATIONS: alpha
      GalCer activation of IFN-gamma-secreting, CD1d-restricted lymphocytes induced
      iNOS-CD95-dependent apoptosis in developing eosinophils. This pathway is
      initiated by endogenous regulatory lymphocytes, antagonised by LTD4 , NSAIDs and
      aminoguanidine, and modified by dexamethasone.

PMID- 25752590
TI  - The long-term development of non-motor problems after STN-DBS.
AB  - OBJECTIVES: Stimulation of the subthalamic nucleus (STN-DBS) is an established
      treatment with long-term beneficial effects on motor symptoms in patients with
      Parkinson's disease (PD). The long-term development of non-motor problems after
      STN-DBS is not fully understood. In this study, we have studied how non-motor
      problems develop in patients with and without STN-DBS. MATERIALS AND METHODS: We
      collected data from a prospectively followed cohort of patients that had been
      operated with STN-DBS 6-9 years before final examination and compared our
      findings to the longitudinal development of non-motor problems in a non-operated,
      comparable reference population. RESULTS: In general, the non-motor problems of
      advanced PD seem to develop independently of treatment with STN-DBS. We found
      that depressions do not worsen after STN-DBS, and the Montgomery and Aasberg
      Depression Rating Scale score in operated patients was substantially reduced from
      pre-operatively to post-operatively. Further, fatigue may represent an important
      unrecognized side effect of long-term stimulation, as fatigue was found to
      increase rapidly in operated patients already a year after surgery and continued
      to increase trough the 6- to 9-year follow-up. CONCLUSIONS: The non-motor
      problems of advanced PD seem to develop independently of treatment with STN-DBS.
      This may influence the strategy for choice of when to perform this therapy for
      eligible patients.

PMID- 25752591
TI  - The application of nitric oxide to control biofouling of membrane bioreactors.
AB  - A novel strategy to control membrane bioreactor (MBR) biofouling using the nitric
      oxide (NO) donor compound PROLI NONOate was examined. When the biofilm was pre
      established on membranes at transmembrane pressure (TMP) of 88-90 kPa,
      backwashing of the membrane module with 80 MUM PROLI NONOate for 45 min once
      daily for 37 days reduced the fouling resistance (Rf ) by 56%. Similarly, a
      daily, 1 h exposure of the membrane to 80 MUM PROLI NONOate from the commencement
      of MBR operation for 85 days resulted in reduction of the TMP and Rf by 32.3% and
      28.2%. The microbial community in the control MBR was observed to change from
      days 71 to 85, which correlates with the rapid TMP increase. Interestingly, NO
      treated biofilms at 85 days had a higher similarity with the control biofilms at
      71 days relative to the control biofilms at 85 days, indicating that the NO
      treatment delayed the development of biofilm bacterial community. Despite this
      difference, sequence analysis indicated that NO treatment did not result in a
      significant shift in the dominant fouling species. Confocal microscopy revealed
      that the biomass of biopolymers and microorganisms in biofilms were all reduced
      on the PROLI NONOate-treated membranes, where there were reductions of 37.7% for
      proteins and 66.7% for microbial cells, which correlates with the reduction in
      TMP. These results suggest that NO treatment could be a promising strategy to
      control biofouling in MBRs. 

PMID- 25752592
TI  - Attentional biases for food cues in overweight and individuals with obesity: a
      systematic review of the literature.
AB  - Obesity rates have increased dramatically in recent decades, and it has proven
      difficult to treat. An attentional bias towards food cues may be implicated in
      the aetiology of obesity and influence cravings and food consumption. This review
      systematically investigated whether attentional biases to food cues exist in
      overweight/obese compared with healthy weight individuals. Electronic database
      were searched for relevant papers from inception to October 2014. Only studies
      reporting food-related attentional bias between either overweight (body mass
      index [BMI] 25.0-29.9 kg m(-2)) or obese (BMI >= 30) participants and healthy
      weight participants (BMI 18.5-24.9) were included. The findings of 19 studies
      were reported in this review. Results of the literature are suggestive of
      differences in attentional bias, with all but four studies supporting the notion
      of enhanced reactivity to food stimuli in overweight individuals and individuals
      with obesity. This support for attentional bias was observed primarily in studies
      that employed psychophysiological techniques (i.e. electroencephalogram, eye
      tracking and functional magnetic resonance imaging). Despite the heterogeneous
      methodology within the featured studies, all measures of attentional bias
      demonstrated altered cue-reactivity in individuals with obesity. Considering the
      theorized implications of attentional biases on obesity pathology, researchers
      are encouraged to replicate flagship studies to strengthen these inferences.

PMID- 25752593
TI  - Unusual angular dependence of the Raman response in black phosphorus.
AB  - Anisotropic materials are characterized by a unique optical response, which is
      highly polarization-dependent. Of particular interest are layered materials
      formed by the stacking of two-dimensional (2D) crystals that are naturally
      anisotropic in the direction perpendicular to the 2D planes. Black phosphorus
      (BP) is a stack of 2D phosphorene crystals and a highly anisotropic semiconductor
      with a direct band gap. We show that the angular dependence of polarized Raman
      spectra of BP is rather unusual and can be explained only by considering complex
      values for the Raman tensor elements. This result can be traced back to the
      electron-photon and electron-phonon interactions in this material. 

PMID- 25752594
TI  - Impact of perinatal health and socio-demographic factors on school education
      outcomes: A population study of Indigenous and non-Indigenous children in the
      Northern Territory.
AB  - AIM: This study investigated the association between early-life risk factors and
      school education outcomes. METHODS: This is an historical cohort study of 7601
      children (61% were Indigenous) born in the Northern Territory between 1999 and
      2004. Information was linked, for each child on: perinatal health, student
      enrolment and National Assessment Program - Literacy and Numeracy (NAPLAN) Year 3
      results. Logistic regression was used to estimate the association between
      selected risk factors and a NAPLAN result 'below' the national minimum standard
      (NMS) in reading and numeracy. RESULTS: Indigenous children had much higher odds,
      than non-Indigenous children, of a result below the NMS for both reading (odds
      ratio (OR): 8.58, 95% confidence interval (CI): 7.55-9.74) ) and numeracy (OR:
      11.52, 95% CI: 9.94-13.35). When adjusted for all other variables, the increased
      odds were attenuated for both reading (OR: 2.89, 95% CI: 2.46-3.40) and numeracy
      (OR: 3.19, 95% CI: 2.65-3.84). Common risk factors for Indigenous and non
      Indigenous children included higher birth order, maternal smoking in pregnancy
      and being a boy. There were gradients of decreasing risk with increasing
      education level of primary care giver and increasing maternal age. Among
      Indigenous children only, risks increased when living in remote areas, with
      younger age (<8 years) and low birthweight. CONCLUSIONS: The study highlights
      that many of the risk factors associated with poor education outcomes among
      Indigenous children are shared with the general population. The results inform a
      targeted, cross-agency response to address modifiable early-life risk factors for
      educational disadvantage. Data linkage, using existing administrative datasets,
      provides a useful addition to methods that identify priority areas for prevention
      and early intervention.

PMID- 25752595
TI  - Nature and nurture: a case of transcending haematological pre-malignancies in a
      pair of monozygotic twins adding possible clues on the pathogenesis of B-cell
      proliferations.
AB  - We describe a comprehensive molecular analysis of a pair of monozygotic twins,
      who came to our attention when one experienced amaurosis fugax and was diagnosed
      with JAK2+ polycythaemia vera. He (Twin A) was also found to have an asymptomatic
      B-cell chronic lymphocytic leukaemia (B-CLL). Although JAK2-, Twin B was
      subsequently shown to have a benign monoclonal B-cell lymphocytosis (MBL). Flow
      cytometric and molecular analyses of the B-cell compartments revealed different
      immunoglobulin light and heavy chain usage in each twin. We hypothesized that
      whole exome sequencing could help delineating the pattern of germline B-cell
      disorder susceptibility and reveal somatic mutations potentially contributing to
      the differential patterns of pre-malignancy. Comparing bone marrow cells and T
      cells and employing in-house engineered integrative analysis, we found
      aberrations in Twin A consistent with a myeloid neoplasm, i.e. in TET2, RUNX1,
      PLCB1 and ELF4. Employing the method for detecting high-ranking variants by
      extensive annotation and relevance scoring, we also identified shared germline
      variants in genes of proteins interacting with B-cell receptor signalling
      mediators and the WNT-pathway, including IRF8, PTPRO, BCL9L, SIT1 and SIRPB1, all
      with possible implications in B-cell proliferation. Similar patterns of IGHV-gene
      usage to those demonstrated here have been observed in inherited acute
      lymphoblastic leukaemia. Collectively, these findings may help in facilitating
      identification of putative master gene(s) involved in B-cell proliferations in
      general and MBL and B-CLL in particular. 

PMID- 25752596
TI  - WHO'S IN CHARGE? THE RELATIONSHIP BETWEEN MEDICAL LAW, MEDICAL ETHICS, AND
      MEDICAL MORALITY?
AB  - Medical law inevitably involves decision-making, but the types of decisions that
      need to be made vary in nature, from those that are purely technical to others
      that contain an inherent ethical content. In this paper we identify the different
      types of decisions that need to be made, and explore whether the law, the medical
      profession, or the individual doctor is best placed to make them. We also argue
      that the law has failed in its duty to create a coherent foundation from which
      such decision-making might properly be regulated, and this has resulted in a
      haphazard legal framework that contains no consistency. We continue by examining
      various medico-legal topics in relation to these issues before ending by
      considering the risk of demoralisation. 

PMID- 25752597
TI  - In Silico Post Genome-Wide Association Studies Analysis of C-Reactive Protein
      Loci Suggests an Important Role for Interferons.
AB  - BACKGROUND: Genome-wide association studies (GWASs) have successfully identified
      several single nucleotide polymorphisms (SNPs) associated with serum levels of C
      reactive protein (CRP). An important limitation of GWASs is that the identified
      variants merely flag the nearby genomic region and do not necessarily provide a
      direct link to the biological mechanisms underlying their corresponding
      phenotype. Here we apply a bioinformatics-based approach to uncover the
      functional characteristics of the 18 SNPs that had previously been associated
      with CRP at a genome-wide significant level. METHODS AND RESULTS: In the first
      phase of in silico sequencing, we explore the vicinity of GWAS SNPs to identify
      all linked variants. In the second phase of expression quantitative trait loci
      analysis, we attempt to identify all nearby genes whose expression levels are
      associated with the corresponding GWAS SNPs. These 2 phases generate several
      relevant genes that serve as input to the next phase of functional network
      analysis. Our in silico sequencing analysis using 1000 Genomes Project data
      identified 7 nonsynonymous SNPs, which are in moderate to high linkage
      disequilibrium (r(2)>0.5) with the GWAS SNPs. Our expression quantitative trait
      loci analysis, which was based on one of the largest single data sets of genome
      wide expression probes (n>5000) identified 23 significantly associated expression
      probes belonging to 15 genes (false discovery rate <0.01). The final phase of
      functional network analysis revealed 93 significantly enriched biological
      processes (false discovery rate <0.01). CONCLUSIONS: Our post-GWAS analysis of
      CRP GWAS SNPs confirmed the previously known overlap between CRP and lipids
      biology. Additionally, it suggested an important role for interferons in the
      metabolism of CRP.

PMID- 25752598
TI  - More children showing early signs of serious diabetes complications, audit finds.

PMID- 25752599
TI  - Visualizing the global secondary structure of a viral RNA genome with cryo
      electron microscopy.
AB  - The lifecycle, and therefore the virulence, of single-stranded (ss)-RNA viruses
      is regulated not only by their particular protein gene products, but also by the
      secondary and tertiary structure of their genomes. The secondary structure of the
      entire genomic RNA of satellite tobacco mosaic virus (STMV) was recently
      determined by selective 2'-hydroxyl acylation analyzed by primer extension
      (SHAPE). The SHAPE analysis suggested a single highly extended secondary
      structure with much less branching than occurs in the ensemble of structures
      predicted by purely thermodynamic algorithms. Here we examine the solution
      equilibrated STMV genome by direct visualization with cryo-electron microscopy
      (cryo-EM), using an RNA of similar length transcribed from the yeast genome as a
      control. The cryo-EM data reveal an ensemble of branching patterns that are
      collectively consistent with the SHAPE-derived secondary structure model. Thus,
      our results both elucidate the statistical nature of the secondary structure of
      large ss-RNAs and give visual support for modern RNA structure determination
      methods. Additionally, this work introduces cryo-EM as a means to distinguish
      between competing secondary structure models if the models differ significantly
      in terms of the number and/or length of branches. Furthermore, with the latest
      advances in cryo-EM technology, we suggest the possibility of developing methods
      that incorporate restraints from cryo-EM into the next generation of algorithms
      for the determination of RNA secondary and tertiary structures. 

PMID- 25752601
TI  - Understanding communication and coordination among government and service
      organisations after a disaster.
AB  - The purpose of this study is to discover how coordination and communication
      between the government and service organisations responsible for the relief
      effort following Hurricane Katrina contributed to the poor outcomes for the
      communities impacted by the storm. Two hypotheses were tested in this study:
      communication was positively correlated with the degree of coordination
      immediately following Katrina; and miscommunication was negatively correlated
      with the degree of coordination after the storm. Quantitative content analysis of
      media reports was used to analyse the data and test the hypotheses. Both
      communication and miscommunication were found to be positively correlated with
      coordination. The results of this study suggest that increasing
      interorganisational communication and establishing clearly defined roles for
      organisations must be a high priority in revamping organisational protocol on
      disaster response if any new approach is to be successful. 

PMID- 25752600
TI  - OASes and STING: adaptive evolution in concert.
AB  - OAS (2'-5'-oligoadenylate synthases) proteins and cyclic GMP-AMP synthase (cGAS,
      gene symbol: MB21D1) patrol the cytoplasm for the presence of foreign nucleic
      acids. Upon binding to double-stranded RNA or double-stranded DNA, OAS proteins
      and cGAS produce nucleotide second messengers to activate RNase L and STING
      (stimulator of interferon genes, gene symbol: TMEM173), respectively; this leads
      to the initiation of antiviral responses. We analyzed the evolutionary history of
      the MB21D1-TMEM173 and OAS-RNASEL axes in primates and bats and found evidence of
      widespread positive selection in both orders. In TMEM173, residue 230, a major
      determinant of response to natural ligands and to mimetic drugs (e.g., DMXAA),
      was positively selected in Primates and Chiroptera. In both orders, selection
      also targeted an alpha-helix/loop element in RNase L that modulates the enzyme
      preference for single-stranded RNA versus stem loops. Analysis of positively
      selected sites in OAS1, OAS2, and MB21D1 revealed parallel evolution, with the
      corresponding residues being selected in different genes. As this cannot result
      from gene conversion, these data suggest that selective pressure acting on OAS
      and MB21D1 genes is related to nucleic acid recognition and to the specific
      mechanism of enzyme activation, which requires a conformational change. Finally,
      a population genetics-phylogenetics analysis in humans, chimpanzees, and gorillas
      detected several positively selected sites in most genes. Data herein shed light
      into species-specific differences in infection susceptibility and in response to
      synthetic compounds, with relevance for the design of synthetic compounds as
      vaccine adjuvants. 

PMID- 25752603
TI  - Active site and laminarin binding in glycoside hydrolase family 55.
AB  - The Carbohydrate Active Enzyme (CAZy) database indicates that glycoside hydrolase
      family 55 (GH55) contains both endo- and exo-beta-1,3-glucanases. The founding
      structure in the GH55 is PcLam55A from the white rot fungus Phanerochaete
      chrysosporium (Ishida, T., Fushinobu, S., Kawai, R., Kitaoka, M., Igarashi, K.,
      and Samejima, M. (2009) Crystal structure of glycoside hydrolase family 55 beta
      1,3-glucanase from the basidiomycete Phanerochaete chrysosporium. J. Biol. Chem.
      284, 10100-10109). Here, we present high resolution crystal structures of
      bacterial SacteLam55A from the highly cellulolytic Streptomyces sp. SirexAA-E
      with bound substrates and product. These structures, along with mutagenesis and
      kinetic studies, implicate Glu-502 as the catalytic acid (as proposed earlier for
      Glu-663 in PcLam55A) and a proton relay network of four residues in activating
      water as the nucleophile. Further, a set of conserved aromatic residues that
      define the active site apparently enforce an exo-glucanase reactivity as
      demonstrated by exhaustive hydrolysis reactions with purified
      laminarioligosaccharides. Two additional aromatic residues that line the
      substrate-binding channel show substrate-dependent conformational flexibility
      that may promote processive reactivity of the bound oligosaccharide in the
      bacterial enzymes. Gene synthesis carried out on ~30% of the GH55 family gave 34
      active enzymes (19% functional coverage of the nonredundant members of GH55).
      These active enzymes reacted with only laminarin from a panel of 10 different
      soluble and insoluble polysaccharides and displayed a broad range of specific
      activities and optima for pH and temperature. Application of this experimental
      method provides a new, systematic way to annotate glycoside hydrolase
      phylogenetic space for functional properties. 

PMID- 25752604
TI  - Variable Substrate Preference among Phospholipase D Toxins from Sicariid Spiders.
AB  - Venoms of the sicariid spiders contain phospholipase D enzyme toxins that can
      cause severe dermonecrosis and even death in humans. These enzymes convert
      sphingolipid and lysolipid substrates to cyclic phosphates by activating a
      hydroxyl nucleophile present in both classes of lipid. The most medically
      relevant substrates are thought to be sphingomyelin and/or
      lysophosphatidylcholine. To better understand the substrate preference of these
      toxins, we used (31)P NMR to compare the activity of three related but
      phylogenetically diverse sicariid toxins against a diverse panel of sphingolipid
      and lysolipid substrates. Two of the three showed significantly faster turnover
      of sphingolipids over lysolipids, and all three showed a strong preference for
      positively charged (choline and/or ethanolamine) over neutral (glycerol and
      serine) headgroups. Strikingly, however, the enzymes vary widely in their
      preference for choline, the headgroup of both sphingomyelin and
      lysophosphatidylcholine, versus ethanolamine. An enzyme from Sicarius terrosus
      showed a strong preference for ethanolamine over choline, whereas two paralogous
      enzymes from Loxosceles arizonica either preferred choline or showed no
      significant preference. Intrigued by the novel substrate preference of the
      Sicarius enzyme, we solved its crystal structure at 2.1 A resolution. The
      evolution of variable substrate specificity may help explain the reduced
      dermonecrotic potential of some natural toxin variants, because mammalian
      sphingolipids use primarily choline as a positively charged headgroup; it may
      also be relevant for sicariid predatory behavior, because ethanolamine-containing
      sphingolipids are common in insect prey. 

PMID- 25752605
TI  - Tadalafil Integrates Nitric Oxide-Hydrogen Sulfide Signaling to Inhibit High
      Glucose-induced Matrix Protein Synthesis in Podocytes.
AB  - Diabetes-induced kidney cell injury involves an increase in matrix protein
      expression that is only partly alleviated by current treatment, prompting a
      search for new modalities. We have previously shown that hydrogen sulfide (H2S)
      inhibits high glucose-induced protein synthesis in kidney podocytes. We tested
      whether tadalafil, a phosphodiesterase 5 inhibitor used to treat erectile
      dysfunction, ameliorates high glucose stimulation of matrix proteins by
      generating H2S in podocytes. Tadalafil abrogated high glucose stimulation of
      global protein synthesis and matrix protein laminin gamma1. Tadalafil inhibited
      high glucose-induced activation of mechanistic target of rapamycin complex 1 and
      laminin gamma1 accumulation in an AMP-activated protein kinase (AMPK)-dependent
      manner. Tadalafil increased AMPK phosphorylation by stimulating calcium
      calmodulin kinase kinase beta. Tadalafil rapidly increased the expression and
      activity of the H2S-generating enzyme cystathionine gamma-lyase (CSE) by
      promoting its translation. dl-Propargylglycine, a CSE inhibitor, and siRNA
      against CSE inhibited tadalafil-induced AMPK phosphorylation and abrogated the
      tadalafil effect on high glucose stimulation of laminin gamma1. In tadalafil
      treated podocytes, we examined the interaction between H2S and nitric oxide (NO).
      N(omega)-Nitro-L-arginine methyl ester and 1H-[1,2,4]-oxadiazolo-[4,3-a]
      quinoxalin-1-one, inhibitors of NO synthase (NOS) and soluble guanylyl cyclase,
      respectively, abolished tadalafil induction of H2S and AMPK phosphorylation.
      Tadalafil rapidly augmented inducible NOS (iNOS) expression by increasing its
      mRNA, and siRNA for iNOS and 1400W, an iNOS blocker, inhibited tadalafil
      stimulation of CSE expression and AMPK phosphorylation. We conclude that
      tadalafil amelioration of high glucose stimulation of synthesis of proteins
      including matrix proteins in podocytes requires integration of the NO-H2S-AMPK
      axis leading to the inhibition of high glucose-induced mechanistic target of
      rapamycin complex 1 activity and mRNA translation.

PMID- 25752606
TI  - Corynebacterium diphtheriae methionine sulfoxide reductase a exploits a unique
      mycothiol redox relay mechanism.
AB  - Methionine sulfoxide reductases are conserved enzymes that reduce oxidized
      methionines in proteins and play a pivotal role in cellular redox signaling. We
      have unraveled the redox relay mechanisms of methionine sulfoxide reductase A of
      the pathogen Corynebacterium diphtheriae (Cd-MsrA) and shown that this enzyme is
      coupled to two independent redox relay pathways. Steady-state kinetics combined
      with mass spectrometry of Cd-MsrA mutants give a view of the essential cysteine
      residues for catalysis. Cd-MsrA combines a nucleophilic cysteine sulfenylation
      reaction with an intramolecular disulfide bond cascade linked to the thioredoxin
      pathway. Within this cascade, the oxidative equivalents are transferred to the
      surface of the protein while releasing the reduced substrate. Alternatively, MsrA
      catalyzes methionine sulfoxide reduction linked to the mycothiol/mycoredoxin-1
      pathway. After the nucleophilic cysteine sulfenylation reaction, MsrA forms a
      mixed disulfide with mycothiol, which is transferred via a thiol disulfide relay
      mechanism to a second cysteine for reduction by mycoredoxin-1. With x-ray
      crystallography, we visualize two essential intermediates of the thioredoxin
      relay mechanism and a cacodylate molecule mimicking the substrate interactions in
      the active site. The interplay of both redox pathways in redox signaling
      regulation forms the basis for further research into the oxidative stress
      response of this pathogen. 

PMID- 25752607
TI  - Membrane and integrative nuclear fibroblastic growth factor receptor (FGFR)
      regulation of FGF-23.
AB  - Fibroblastic growth factor receptor 1 (FGFR1) signaling pathways are implicated
      in the regulation of FGF-23 gene transcription, but the molecular pathways remain
      poorly defined. We used low molecular weight (LMW, 18 kDa) FGF-2 and high
      molecular weight (HMW) FGF-2 isoforms, which, respectively, activate cell surface
      FGF receptors and intranuclear FGFR1, to determine the roles of membrane FGFRs
      and integrative nuclear FGFR1 signaling (INFS) in the regulation of FGF-23 gene
      transcription in osteoblasts. We found that LMW-FGF-2 induced NFAT and Ets1
      binding to conserved cis-elements in the proximal FGF-23 promoter and stimulated
      FGF-23 promoter activity through PLCgamma/calcineurin/NFAT and MAPK pathways in
      SaOS-2 and MC3T3-E1 osteoblasts. In contrast, HMW-FGF-2 stimulated FGF-23
      promoter activity in osteoblasts through a cAMP-dependent binding of FGFR1 and
      cAMP-response element-binding protein (CREB) to a conserved cAMP response element
      (CRE) contiguous with the NFAT binding site in the FGF-23 promoter. Mutagenesis
      of the NFAT and CRE binding sites, respectively, inhibited the effects of LMW-FGF
      2 and HMW-FGF-23 to stimulate FGF-23 promoter activity. FGF-2 activation of both
      membrane FGFRs and INFS-dependent FGFR1 pathways may provide a means to integrate
      systemic and local regulation of FGF-23 transcription under diverse physiological
      and pathological conditions. 

PMID- 25752608
TI  - Transient intermediates in enzymology, 1964-2008.

PMID- 25752609
TI  - Apoptosis Signal-regulating Kinase 1 (ASK1)-p38 Pathway-dependent Cytoplasmic
      Translocation of the Orphan Nuclear Receptor NR4A2 Is Required for Oxidative
      Stress-induced Necrosis.
AB  - p38 mitogen-activated protein kinases (MAPKs) play important roles in various
      cellular stress responses, including cell death, which is roughly categorized
      into apoptosis and necrosis. Although p38 signaling has been extensively studied,
      the molecular mechanisms of p38-mediated cell death are unclear. ASK1 is a stress
      responsive MAP3K that acts as an upstream kinase of p38 and is activated by
      various stresses, such as oxidative stress. Here, we show that NR4A2, a member of
      the NR4A nuclear receptor family, acts as a necrosis promoter downstream of ASK1
      p38 pathway during oxidative stress. Although NR4A2 is well known as a nucleus
      localized transcription factor, we found that it is translocated into the cytosol
      after phosphorylation by p38. Because the phosphorylation site mutants of NR4A2
      cannot rescue the cell death-promoting activity, ASK1-p38 pathway-dependent
      phosphorylation and subsequent cytoplasmic translocation of NR4A2 may be required
      for oxidative stress-induced cell death. In addition, NR4A2-mediated cell death
      does not depend on caspases and receptor-interacting protein 1 (RIP1)-RIP3
      complex, suggesting that NR4A2 promotes an RIP kinase-independent necrotic type
      of cell death. Our findings may enable a more precise understanding of molecular
      mechanisms that regulate oxidative stress-induced and p38-mediated necrosis. 

PMID- 25752610
TI  - UreE-UreG complex facilitates nickel transfer and preactivates GTPase of UreG in
      Helicobacter pylori.
AB  - The pathogenicity of Helicobacter pylori relies heavily on urease, which converts
      urea to ammonia to neutralize the stomach acid. Incorporation of Ni(2+) into the
      active site of urease requires a battery of chaperones. Both metallochaperones
      UreE and UreG play important roles in the urease activation. In this study, we
      demonstrate that, in the presence of GTP and Mg(2+), UreG binds Ni(2+) with an
      affinity (Kd) of ~0.36 MUm. The GTPase activity of Ni(2+)-UreG is stimulated by
      both K(+) (or NH4 (+)) and HCO3 (-) to a biologically relevant level, suggesting
      that K(+)/NH4 (+) and HCO3 (-) might serve as GTPase elements of UreG. We show
      that complexation of UreE and UreG results in two protein complexes, i.e. 2E-2G
      and 2E-G, with the former being formed only in the presence of both GTP and
      Mg(2+). Mutagenesis studies reveal that Arg-101 on UreE and Cys-66 on UreG are
      critical for stabilization of 2E-2G complex. Combined biophysical and bioassay
      studies show that the formation of 2E-2G complex not only facilitates nickel
      transfer from UreE to UreG, but also enhances the binding of GTP. This suggests
      that UreE might also serve as a structural scaffold for recruitment of GTP to
      UreG. Importantly, we demonstrate for the first time that UreE serves as a bridge
      to grasp Ni(2+) from HypA, subsequently donating it to UreG. The study expands
      our horizons on the molecular details of nickel translocation among
      metallochaperones UreE, UreG, and HypA, which further extends our knowledge on
      the urease maturation process. 

PMID- 25752611
TI  - Chronic Deletion and Acute Knockdown of Parkin Have Differential Responses to
      Acetaminophen-induced Mitophagy and Liver Injury in Mice.
AB  - We previously demonstrated that pharmacological induction of autophagy protected
      against acetaminophen (APAP)-induced liver injury in mice by clearing damaged
      mitochondria. However, the mechanism for removal of mitochondria by autophagy is
      unknown. Parkin, an E3 ubiquitin ligase, has been shown to be required for
      mitophagy induction in cultured mammalian cells following mitochondrial
      depolarization, but its role in vivo is not clear. The purpose of this study was
      to investigate the role of Parkin-mediated mitophagy in protection against APAP
      induced liver injury. We found that Parkin translocated to mitochondria in mouse
      livers after APAP treatment followed by mitochondrial protein ubiquitination and
      mitophagy induction. To our surprise, we found that mitophagy still occurred in
      Parkin knock-out (KO) mice after APAP treatment based on electron microscopy
      analysis and Western blot analysis for some mitochondrial proteins, and Parkin KO
      mice were protected against APAP-induced liver injury compared with wild type
      mice. Mechanistically, we found that Parkin KO mice had decreased activated c-Jun
      N-terminal kinase (JNK), increased induction of myeloid leukemia cell
      differentiation protein (Mcl-1) expression, and increased hepatocyte
      proliferation after APAP treatment in their livers compared with WT mice. In
      contrast to chronic deletion of Parkin, acute knockdown of Parkin in mouse livers
      using adenovirus shRNA reduced mitophagy and Mcl-1 expression but increased JNK
      activation after APAP administration, which exacerbated APAP-induced liver
      injury. Therefore, chronic deletion (KO) and acute knockdown of Parkin have
      differential responses to APAP-induced mitophagy and liver injury in mice. 

PMID- 25752612
TI  - Structural and biochemical characterization of a novel aminopeptidase from human
      intestine.
AB  - N-acetylated alpha-linked acidic dipeptidase-like protein (NAALADase L), encoded
      by the NAALADL1 gene, is a close homolog of glutamate carboxypeptidase II, a
      metallopeptidase that has been intensively studied as a target for imaging and
      therapy of solid malignancies and neuropathologies. However, neither the
      physiological functions nor structural features of NAALADase L are known at
      present. Here, we report a thorough characterization of the protein product of
      the human NAALADL1 gene, including heterologous overexpression and purification,
      structural and biochemical characterization, and analysis of its expression
      profile. By solving the NAALADase L x-ray structure, we provide the first
      experimental evidence that it is a zinc-dependent metallopeptidase with a
      catalytic mechanism similar to that of glutamate carboxypeptidase II yet distinct
      substrate specificity. A proteome-based assay revealed that the NAALADL1 gene
      product possesses previously unrecognized aminopeptidase activity but no carboxy-
      or endopeptidase activity. These findings were corroborated by site-directed
      mutagenesis and identification of bestatin as a potent inhibitor of the enzyme.
      Analysis of NAALADL1 gene expression at both the mRNA and protein levels revealed
      the small intestine as the major site of protein expression and points toward
      extensive alternative splicing of the NAALADL1 gene transcript. Taken together,
      our data imply that the NAALADL1 gene product's primary physiological function is
      associated with the final stages of protein/peptide digestion and absorption in
      the human digestive system. Based on these results, we suggest a new name for
      this enzyme: human ileal aminopeptidase (HILAP). 

PMID- 25752613
TI  - High structural resolution hydroxyl radical protein footprinting reveals an
      extended Robo1-heparin binding interface.
AB  - Interaction of transmembrane receptors of the Robo family and the secreted
      protein Slit provides important signals in the development of the central nervous
      system and regulation of axonal midline crossing. Heparan sulfate, a sulfated
      linear polysaccharide modified in a complex variety of ways, serves as an
      essential co-receptor in Slit-Robo signaling. Previous studies have shown that
      closely related heparin octasaccharides bind to Drosophila Robo directly, and
      surface plasmon resonance analysis revealed that Robo1 binds more tightly to full
      length unfractionated heparin. For the first time, we utilized electron transfer
      dissociation-based high spatial resolution hydroxyl radical protein footprinting
      to identify two separate binding sites for heparin interaction with Robo1: one
      binding site at the previously identified site for heparin dp8 and a second
      binding site at the N terminus of Robo1 that is disordered in the x-ray crystal
      structure. Mutagenesis of the identified N-terminal binding site exhibited a
      decrease in binding affinity as measured by surface plasmon resonance and heparin
      affinity chromatography. Footprinting also indicated that heparin binding induces
      a minor change in the conformation and/or dynamics of the Ig2 domain, but no
      major conformational changes were detected. These results indicate a second low
      affinity binding site in the Robo-Slit complex as well as suggesting the role of
      the Ig2 domain of Robo1 in heparin-mediated signal transduction. This study also
      marks the first use of electron transfer dissociation-based high spatial
      resolution hydroxyl radical protein footprinting, which shows great utility for
      the characterization of protein-carbohydrate complexes. 

PMID- 25752614
TI  - A highly sensitive quantification method for the accumulation of alarmone ppGpp
      in Arabidopsis thaliana using UPLC-ESI-qMS/MS.
AB  - Recently, a bacterial second messenger, guanosine 5'-diphosphate 3'-diphosphate
      (ppGpp), has been detected in chloroplasts. However, because ppGpp concentration
      in plants is much lower than that in bacteria, detailed analysis of ppGpp in
      plants has not been performed. A highly sensitive quantification method is
      required for further characterization of ppGpp function in chloroplasts. Here, we
      report a new method that allows for the highly sensitive and selective high
      throughput quantification of ppGpp by ultra-performance liquid chromatography
      (UPLC) coupled with a tandem quadrupole mass spectrometer (qMS/MS) equipped with
      an electrospray interface (ESI). This method requires only ~100 mg of plant
      tissue for ppGpp quantification. We used this method to measure ppGpp levels in
      Arabidopsis thaliana under different light conditions. A. thaliana accumulated
      ppGpp during dark periods. This method will be helpful to further characterize
      the stringent response in higher plants. 

PMID- 25752615
TI  - Gender differences in stroke prevention in atrial fibrillation in general
      practice: using the GRASP-AF audit tool.
AB  - BACKGROUND: Women represent a large proportion of patients with atrial
      fibrillation (AF) and tend to have higher risk of stroke. AIMS: This study
      examines gender differences in the utilisation of oral anticoagulation (OAC) and
      prognosis (i.e. stroke and death) in AF patients in UK general practice. DESIGN:
      Retrospective observational study. METHODS: The Guidance on Risk Assessment and
      Stroke Prevention in Atrial Fibrillation (GRASP-AF) tool was employed to identify
      AF patients from 11 general practices in Darlington, England. RESULTS: Two
      thousand two hundred and fifty-nine AF patients (mean+/-SD age 76 +/- 12 years;
      46% female) were identified. Based on CHA2 DS2 -VASc score 95% of women and 90%
      of men were at moderate-high risk of stroke. Women with moderate-high risk of
      stroke were treated with OAC less frequently than men (47% vs. 52%, p = 0.006).
      Overall rates of stroke and all-cause mortality were higher among women than men
      (p = 0.02 and p < 0.001). However, there was no significant gender difference in
      these outcomes in patients receiving OAC (p = 0.52 for stroke, p = 0.18 for
      death). Among people not receiving OAC where indicated, female gender was
      associated with an increased risk of stroke before (p = 0.01), and after (p =
      0.04), adjustment for stroke risk factors. Women not receiving OAC had a higher
      risk of death on univariate regression analysis (p = 0.002), but not after
      adjustment for stroke risk factors (p = 0.53). CONCLUSION: Women with AF are at
      higher risk of stroke than men without OAC. The gender-related differences in
      risk of stroke disappear if OAC is used. Despite this, women are more likely not
      to receive OAC.

PMID- 25752618
TI  - Linking degradation status with ecosystem vulnerability to environmental change.
AB  - Environmental change can cause regime shifts in ecosystems, potentially
      threatening ecosystem services. It is unclear if the degradation status of
      ecosystems correlates with their vulnerability to environmental change, and thus
      the risk of future regime shifts. We assessed resilience in acidified (degraded)
      and circumneutral (undegraded) lakes with long-term data (1988-2012), using time
      series modeling. We identified temporal frequencies in invertebrate assemblages,
      which identifies groups of species whose population dynamics vary at particular
      temporal scales. We also assessed species with stochastic dynamics, those whose
      population dynamics vary irregularly and unpredictably over time. We determined
      the distribution of functional feeding groups of invertebrates within and across
      the temporal scales identified, and in those species with stochastic dynamics,
      and assessed attributes hypothesized to contribute to resilience. Three patterns
      of temporal dynamics, consistent across study lakes, were identified in the
      invertebrates. The first pattern was one of monotonic change associated with
      changing abiotic lake conditions. The second and third patterns appeared
      unrelated to the environmental changes we monitored. Acidified and the
      circumneutral lakes shared similar levels and patterns of functional richness,
      evenness, diversity, and redundancy for species within and across the observed
      temporal scales and for stochastic species groups. These similar resilience
      characteristics suggest that both lake types did not differ in vulnerability to
      the environmental changes observed here. Although both lake types appeared
      equally vulnerable in this study, our approach demonstrates how assessing
      systemic vulnerability by quantifying ecological resilience can help address
      uncertainty in predicting ecosystem responses to environmental change across
      ecosystems. 

PMID- 25752617
TI  - Biome-specific effects of nitrogen and phosphorus on the photosynthetic
      characteristics of trees at a forest-savanna boundary in Cameroon.
AB  - Photosynthesis/nutrient relationships of proximally growing forest and savanna
      trees were determined in an ecotonal region of Cameroon (Africa). Although area
      based foliar N concentrations were typically lower for savanna trees, there was
      no difference in photosynthetic rates between the two vegetation formation types.
      Opposite to N, area-based P concentrations were-on average-slightly lower for
      forest trees; a dependency of photosynthetic characteristics on foliar P was only
      evident for savanna trees. Thus savanna trees use N more efficiently than their
      forest counterparts, but only in the presence of relatively high foliar P. Along
      with some other recent studies, these results suggest that both N and P are
      important modulators of woody tropical plant photosynthetic capacities,
      influencing photosynthetic metabolism in different ways that are also biome
      specific. Attempts to find simple unifying equations to describe woody tropical
      vegetation photosynthesis-nutrient relationships are likely to meet with failure,
      with ecophysiological distinctions between forest and savanna requiring
      acknowledgement. 

PMID- 25752616
TI  - Comparison of different approaches to calculate nutrient intakes based upon 24-h
      recall data derived from a multicenter study in European adolescents.
AB  - PURPOSE: The European "Healthy Lifestyle in Europe by Nutrition in Adolescence"
      (HELENA) project evaluated two different approaches to harmonize the matching
      procedures between 24-h recall data and food composition databases. In the first
      approach, the 24-h recall data were linked to the local/national food composition
      databases using standardized procedures, while in the second approach, the 24-h
      recall data were linked to the German BLS database which includes a larger food
      list. The aim of this paper was to compare the intakes of energy and eight
      nutrient components calculated via both approaches. METHODS: Two non-consecutive
      24-h recalls were performed in 1268 adolescents. Energy, carbohydrates, proteins,
      fat, fiber, water, alcohol, calcium and vitamin C were calculated via the two
      approaches at individual level. Paired samples t test and Pearson's correlations
      were used to compare the mean intakes of energy and the eight mentioned nutrients
      and to investigate the possible associations between the two approaches. RESULTS:
      Small but significant differences were found between the intakes of energy and
      the eight food components when comparing both approaches. Very strong and strong
      correlations (0.70-0.95) were found between both methods for all nutrients.
      CONCLUSION: The dietary intakes obtained via the two different linking procedures
      are highly correlated for energy and the eight nutrients under study.

PMID- 25752619
TI  - 7,8-Dihydroxy-4-methylcoumarin provides neuroprotection by increasing hippocalcin
      expression.
AB  - 7,8-Dihydroxy-4-methylcoumarin (Dhmc) is a precursor in the synthesis of
      derivatives of 4-methyl coumarin, which has excellent radical scavenging
      properties. In this study, we investigated whether Dhmc protects against
      oxidative stress and ischemic brain injury. We found that Dhmc protected against
      glutamate toxicity in hippocampal HT-22 cells in a concentration-dependent manner
      in vitro. Dhmc inhibited glutamate-induced glutathione depletion and generation
      of reactive oxygen species, suggesting that Dhmc has an antioxidant effect. In
      addition, Dhmc inhibited glutamate-induced depletion of hippocalcin, a protein
      that buffers intracellular calcium and prevents calcium-induced cell death. In
      our in vivo studies, Dhmc reduced infarct volume in neonatal rats when
      administered 4 h after cerebral hypoxia/ischemia injury and attenuated the
      hypoxia/ischemia injury-induced decrease of hippocalcin expression in neonatal
      rats. Taken together, these results suggest that Dhmc prevents glutamate-induced
      toxicity by scavenging free radicals and regulating hippocalcin expression. Dhmc
      may represent a promising agent in the treatment of acute and chronic
      neurological disorders induced by oxidative stress.

PMID- 25752620
TI  - Cyanidin-3-O-Glucoside Ameliorates Lipopolysaccharide-Induced Injury Both In Vivo
      and In Vitro Suppression of NF-kappaB and MAPK Pathways.
AB  - Cyanidin-3-O-glucoside (C3G), an anthocyanin belonging to the flavonoid family
      and commonly present in food and vegetables in human diet, has exhibited anti
      inflammatory and anti-oxidant effects. This study aimed to investigate the
      protective ability of C3G against inflammatory and oxidative injuries, as well as
      to clarify the possible mechanism in lipopolysaccharide (LPS)-stimulated human
      umbilical vein endothelial cells (HUVECs) in vitro and acute respiratory distress
      syndrome mouse model in vivo. HUVECs or male Kunming mice were pretreated with
      C3G 1 h before LPS stimulation. C3G significantly inhibited the production of pro
      inflammatory cytokines (tumor necrosis factor-alpha, interleukin (IL) -6, and IL
      1beta) in cell supernatants and bronchoalveolar lavage fluid (BALF) as determined
      by enzyme-linked immunosorbent assay. Histopathologic examination with
      hematoxylin and eosinstaining showed that C3G pretreatment substantially
      suppressed inflammatory cell infiltration, alveolar wall thickening, and
      interstitial edemain lung tissues. C3G markedly prevented LPS-induced elevation
      of malondialdehyde and myeloperoxidase levels in lung tissue homogenates, wet to
      dry ratio of lung tissues, total cells, and inflammatory cells (neutrophils and
      macrophages) in BALF. Moreover, C3G reduced superoxide dismutase activity in the
      lung tissue homogenates. Western blot assay also showed that C3G pretreatment
      significantly suppressed LPS-induced activation of nuclear factor-kappaB (NF
      kappaB) and mitogen-activated protein kinase (MAPK) signaling pathways by
      blocking the phosphorylation of inhibitor kappaB-alpha, NF-kappaB/P65,
      extracellular signal-regulated kinase, p38, and c-Jun NH2-terminal kinase in the
      lung tissues. In summary, C3G may ameliorate LPS-induced injury, which results
      from inflammation and oxidation, by inhibiting NF-kappaB and MAPK pathways and
      playing important anti-inflammatory and anti-oxidative roles.

PMID- 25752621
TI  - Risk of atrial fibrillation among bisphosphonate users: a multicenter, population
      based, Italian study.
AB  - Bisphosphonate treatment is used to prevent bone fractures. A controversial
      association of bisphosphonate use and risk of atrial fibrillation has been
      reported. In our study, current alendronate users were associated with a higher
      risk of atrial fibrillation as compared with those who had stopped bisphosphonate
      (BP) therapy for more than 1 year. INTRODUCTION: Bisphosphonates are widely used
      to prevent bone fractures. Controversial findings regarding the association
      between bisphosphonate use and the risk of atrial fibrillation (AF) have been
      reported. The aim of this study was to evaluate the risk of AF in association
      with BP exposure. METHODS: We performed a nested case-control study using the
      databases of drug-dispensing and hospital discharge diagnoses from five Italian
      regions. The data cover a period ranging from July 1, 2003 to December 31, 2006.
      The study population comprised new users of bisphosphonates aged 55 years and
      older. Patients were followed from the first BP prescription until an occurrence
      of an AF diagnosis (index date, i.e., ID), cancer, death, or the end of the study
      period, whichever came first. For the risk estimation, any AF case was matched by
      age and sex to up to 10 controls from the same source population. A conditional
      logistic regression was performed to obtain the odds ratio with 95% confidence
      intervals (CI). The BP exposure was classified into current (<90 days prior to
      ID), recent (91-180), past (181-364), and distant past (>=365) use, with the
      latter category being used as a reference point. A subgroup analysis by
      individual BP was then carried out. RESULTS: In comparison with distant past
      users of BP, current users of BP showed an almost twofold increased risk of AF:
      odds ratio (OR) = 1.78 and 95% CI = 1.46-2.16. Specifically, alendronate users
      were mostly associated with AF as compared with distant past use of BP (OR, 1.97;
      95% CI, 1.59-2.43). CONCLUSION: In our nested case-control study, current users
      of BP are associated with a higher risk of atrial fibrillation as compared with
      those who had stopped BP treatment for more than 1 year.

PMID- 25752622
TI  - Peripheral quantitative computed tomography (pQCT) reveals low bone mineral
      density in adolescents with motor difficulties.
AB  - This is the first reported study to describe local bone mineral density, assess
      parameters of fracture risk and report history of fractures in adolescents with
      motor difficulties. Motor difficulties evidenced by poor coordination in
      adolescence should be considered a new risk factor for below-average bone
      strength and structure and fracture risk. INTRODUCTION: Adolescents with motor
      difficulties are characterised by poor coordination and low levels of physical
      activity and fitness. It is possible these deficits translate into below-average
      bone strength and structure. The objectives of this study were to describe local
      bone mineral density (BMD), assess parameters of fracture risk (stress-strain
      index, SSI) and report history of fractures in this group. METHODS: Thirty-three
      adolescents (13 females), mean age of 14.3 (SD = 1.5) years, with motor
      difficulties underwent peripheral quantitative computed tomography (pQCT)
      measurements at proximal (66 %) and distal (4 %) sites of the non-dominant radius
      (R4 and R66) and tibia (T4 and T66). One sample t test was used to compare Z
      scores for total BMD, trabecular density, cortical density and stress strain
      index (SSI) against standardized norms. RESULTS: Significant differences were
      present at R4 total density mean Z-score = -0.85 (SD = 0.7, p < 0.001), R66
      cortical density mean Z-score = -0.74 (SD = 1.97, p = 0.038), R66 SSI mean Z
      score = -1.00 (SD = 1.08, p < 0.001) and T66 SSI mean Z-score = -0.70 (SD = 1.15,
      p < 0.001). There was a higher incidence of fractures (26.9 %) compared to the
      normal population (3-9 %). CONCLUSIONS: Motor difficulties in adolescence should
      be considered a risk factor for below-average bone strength and structure and
      fracture risk. Strategies are needed to improve bone health in this high-risk
      group.

PMID- 25752623
TI  - Trabecular bone score may improve FRAX(r) prediction accuracy for major
      osteoporotic fractures in elderly Japanese men: the Fujiwara-kyo Osteoporosis
      Risk in Men (FORMEN) Cohort Study.
AB  - FRAX(r) is widely used to evaluate fracture risk of individuals in clinical
      settings. However, FRAX(r) prediction accuracy is not sufficient, and improvement
      is desired. Trabecular bone score, a bone microarchitecture index, may improve
      FRAX(r) prediction accuracy for major osteoporotic fractures in community
      dwelling elderly Japanese men. INTRODUCTION: To improve fracture risk assessment
      in clinical settings, we evaluated whether the combination of FRAX(r) and
      Trabecular Bone Score (TBS) improves the prediction accuracy of major
      osteoporotic fractures (MOFs) in elderly Japanese men compared to FRAX(r) alone.
      METHODS: Two thousand and twelve community-dwelling men aged >=65 years completed
      the Fujiwara-kyo Osteoporosis Risk in Men (FORMEN) Baseline Study comprising
      lumbar spine (LS) and femoral neck areal bone mineral density (aBMD)
      measurements, and interviews regarding clinical risk factors required to estimate
      10-year risk of MOF (hip, spine, distal forearm, and proximal humerus) using the
      Japanese version of FRAX(r) (v.3.8). TBS was calculated for the same vertebrae
      used for LS-aBMD with TBS iNsight software (v.2.1). MOFs that occurred during the
      follow-up period were identified by interviews or mail and telephone surveys.
      Prediction accuracy of a logistic model combining FRAX(r) score and TBS compared
      to FRAX(r) alone was evaluated by area under receiver-operating characteristic
      curves (AUCs), as well as category-free integrated discrimination improvement
      (IDI) and net reclassification improvement (NRI). RESULTS: We identified 22 men
      with MOFs during 8140 person-years (PY) of follow-up among 1872 men; 67 men who
      suffered from fractures other than MOFs were excluded. Participants with MOFs had
      significantly lower TBS (p = 0.0015) and higher FRAX(r) scores (p = 0.0089) than
      those without. IDI and NRI showed significant improvements in reclassification
      accuracy using FRAX(r) plus TBS compared to FRAX(r) alone (IDI 0.006 (p =
      0.0362), NRI 0.452 (p = 0.0351)), although no difference was observed in AUCs
      between the two. CONCLUSIONS: TBS may improve MOF prediction accuracy of FRAX(r)
      for community-dwelling elderly Japanese men.

PMID- 25752624
TI  - Riboflavin and UV light treatment of platelets: a protective effect of platelet
      additive solution?
AB  - BACKGROUND: Pathogen reduction technologies (PRTs) increase the safety of the
      blood supply, but are also associated with cell damage. Our aim was to
      investigate the effect of Mirasol PRT on platelet (PLT) concentrates stored in
      plasma and whether the use of a PLT additive solution (PAS) is able to improve in
      vitro quality. STUDY DESIGN AND METHODS: Twenty-two buffy coats (BCs) were pooled
      and split into two equal parts. To one half, 2 units of plasma were added, and to
      the other, 2 units of SSP+ PAS were added. Each part was equally split in half
      again (to resemble pooling five BCs) and PLT concentrates were prepared. One
      plasma PLT concentrate was Mirasol treated, and the other served as control;
      similarly, one SSP+ PLT concentrate was Mirasol treated, and the other not. PLT
      concentrates were stored for 8 days (n = 12). RESULTS: Mirasol PRT led to
      elevated lactate production in PLT concentrates in plasma, giving lower pH values
      throughout storage. The use of SSP+ mostly abrogated this effect, and Mirasol
      treated PLT concentrates in SSP+ had only slightly higher lactate production
      rates and annexin A5 binding as control PLT concentrates in plasma. However,
      irrespective whether plasma or SSP+ was used, Mirasol PRT led to higher CD62P
      expression and lower hypotonic shock response (HSR) scores. CONCLUSION: Mirasol
      treatment leads to higher PLT activation and lower HSR scores both when stored in
      plasma or SSP+. However, if Mirasol-treated PLTs are stored in SSP+, lactate
      metabolism and annexin A5 binding are lower, showing that PAS can partly mitigate
      the effect of PRT. The clinical relevance of this finding needs to be
      demonstrated.

PMID- 25752625
TI  - Does the presence of an arteriovenous fistula alter changes in body water
      following hemodialysis as determined by multifrequency bioelectrical impedance
      assessment?
AB  - Multifrequency bioelectrical impedance assessments (MFBIAs) aid clinical
      assessment of hydration status for hemodialysis (HD) patients. Many MFBIA devices
      are restricted to whole body measurements and as many patients dialyze using
      arteriovenous fistulas (AVFs), we wished to determine whether AVFs affected body
      water measurements. We reviewed pre- and post-HD segmental MFBIA measurements in
      229 patients attending for midweek HD sessions. Up to 144 were dialyzed with a
      left arm AVF (L-AVF), 42 with a right arm AVF (R-AVF), and 43 by central venous
      access catheter (CVC). Water content and lean tissue were greater in the left
      compared to right arm in those patients with L-AVFs both pre and post dialysis
      (pre 2.1 +/- 0.7 vs. 2.0 +/- 0.7 L, and post 1.9 +/- 0.6 vs. 1.8 +/- 0.6 L and
      pre 2.65 +/- 0.9 vs. 2.56 +/- 0.8 kg, and post 2.34 +/- 0.8 vs. 2.48 +/- 0.8 vs.
      2.34 +/- 0.8 kg, respectively) and were also greater in the right compared to
      left arm for those patients dialyzing with R-AVFs (pre-HD 1.92 +/- 0.5 vs. 1.86
      +/- 0.6 L and post-HD 1.79 +/- 0.5 vs. 1.7 +/- 0.5 L, and pre-HD 2.47 +/- 0.6 vs.
      2.38 +/- 0.7 kg and post-HD 2.3 +/- 0.74 vs. 1.28 +/- 0.7 kg, respectively), all
      Ps < 0.05. There were no significant differences in arm volumes or composition
      pre or post dialysis in those dialyzing with CVCs. Segmental MFBIA detects
      differences in arm water and lean mass in patients with AVFs. The presence on an
      AVF increases the water content in the ipsilateral arm both pre and post HD. This
      increased water content of the fistula arm will not be detected by whole body
      bioimpedance devices. 

PMID- 25752626
TI  - Topographical variation of macular choroidal thickness with myopia.
AB  - PURPOSE: To study the association between topographical variation of choroidal
      thickness and myopic features in healthy eyes, using spectral domain optical
      coherence tomography (OCT). METHODS: Choroidal thickness was measured at the
      foveal centre (CTF) and 1.5 mm superiorly (CTS), inferiorly (CTI), nasally (CTN)
      and temporally (CTT) from the foveal centre, using enhanced depth imaging OCT.
      The temporal width of beta zone of peripapillary atrophy (betaPPA) was measured
      on infrared fundus images. The ratio of betaPPA width to vertical disc diameter
      (PVDR) was calculated to correct retinal magnification. RESULTS: This study
      includes 85 eyes from 85 subjects who had a mean age of 53.9 +/- 12.9 years, a
      mean axial length of 23.56 +/- 0.82 mm, a mean refractive error of -0.14 +/- 1.80
      D, a mean betaPPA width of 218.6 +/- 181.3 MUm and a mean PVDR of 0.13 +/- 0.11.
      The CTF was thickest (266.4 +/- 81.6), followed by CTS (256.2 +/- 82.5 MUm), CTT
      (251.7 +/- 68.4 MUm), CTI (247.7 +/- 90.3 MUm) and CTN (211.0 +/- 76.5 MUm).
      There were 31 eyes (36.5%) with CTT thicker than CTF. The CTT/CTF negatively
      correlated with refractive error (p = 0.012) and positively correlated with axial
      length (p = 0.031), betaPPA width (p = 0.003) and PVDR (p = 0.006). CONCLUSIONS:
      There was a correlation between a thickened choroid, temporal to the foveal
      centre, with the severity of myopic components in normal eyes. Topographical
      changes might be induced by stretching of the choroid and sclera towards a
      temporal direction with eyeball elongation.

PMID- 25752627
TI  - Distribution and sources of lipid compound series in sediment cores of the
      southern South China Sea.
AB  - Three short sediment cores from inner continental shelf of the southern South
      China Sea (5-50 km) off Terengganu were analyzed for lipid contents (i.e.,
      homologous aliphatic compounds and sterols) using gas chromatography-mass
      spectrometry. The concentrations of the total aliphatic hydrocarbons (TAHs)
      ranged from 0.152 to 6.91 MUg/g dry weight. The n-alkane distribution was from
      nC13 to nC36, with a carbon preference index (CPI13-35) from 1.08 to 4.28 and a
      carbon number maximum (Cmax), depending on a sample, at 31 or 18. In addition, a
      strong odd-to-even carbon number predominance was observed in nC25-nC35 range.
      The distribution of the n-alkanoic acids and n-alkanols in all samples exhibited
      an even-to-odd carbon number predominance and ranged from C10 to C26 and from C12
      to C34, respectively. The n-alkanols were dominated by the long-chain homologs
      with Cmax at 22; on the other hand, the n-alkanoic acid distributions showed a
      predominance of short-chain homologs with a Cmax at 16. The total sterol
      concentrations ranged from 0.41 to 3.57 MUg/g dry weight. Cholesterol was most
      abundant at the offshore stations, whereas sitosterol was dominant at near-shore
      station. Pentacyclic triterpenoids such as friedelin and taraxerol alpha- and
      beta-amyrins, which are known biomarkers for higher plants, were detected at all
      stations with a dilution trend offshore. In conclusion, the marine sediments off
      southern Terengganu can still be considered uncontaminated, where the compound
      sources are biogenic from terrestrial plants superimposed with a marine
      productivity input.

PMID- 25752628
TI  - Alleviation of chromium toxicity by glycinebetaine is related to elevated
      antioxidant enzymes and suppressed chromium uptake and oxidative stress in wheat
      (Triticum aestivum L.).
AB  - Little information is available on the role of glycinebetaine (GB) in chromium
      (Cr) tolerance while Cr toxicity is widespread problem in crops grown on Cr
      contaminated soils. In this study, we investigated the influence of GB on Cr
      tolerance in wheat (Triticum aestivum L.) grown in sand and soil mediums. Three
      concentrations of chromium (0, 0.25, and 0.5 mM) were tested with and without
      foliar application of GB (0.1 M). Chromium alone led to a significant growth
      inhibition and content of chlorophyll a, b, proteins and enhanced the activity of
      antioxidant enzymes. Glycinebetaine foliar application successfully alleviated
      the toxic effects of Cr on wheat plants and enhanced growth characteristics,
      biomass, proteins, and chlorophyll contents. Glycinebetaine also reduced Cr
      accumulation in wheat plants especially in grains and enhanced the activity of
      antioxidant enzymes in both shoots and roots. This study provides evidence that
      GB application contributes to decreased Cr concentrations in wheat plants and its
      importance in the detoxification of heavy metals.

PMID- 25752629
TI  - Application of modified export coefficient method on the load estimation of non
      point source nitrogen and phosphorus pollution of soil and water loss in semiarid
      regions.
AB  - Chinese Loess Plateau is considered as one of the most serious soil loss regions
      in the world, its annual sediment output accounts for 90 % of the total sediment
      loads of the Yellow River, and most of the Loess Plateau has a very typical
      characteristic of "soil and water flow together", and water flow in this area
      performs with a high sand content. Serious soil loss results in nitrogen and
      phosphorus loss of soil. Special processes of water and soil in the Loess Plateau
      lead to the loss mechanisms of water, sediment, nitrogen, and phosphorus are
      different from each other, which are greatly different from other areas of China.
      In this study, the modified export coefficient method considering the rainfall
      erosivity factor was proposed to simulate and evaluate non-point source (NPS)
      nitrogen and phosphorus loss load caused by soil and water loss in the Yanhe
      River basin of the hilly and gully area, Loess Plateau. The results indicate that
      (1) compared with the traditional export coefficient method, annual differences
      of NPS total nitrogen (TN) and total phosphorus (TP) load after considering the
      rainfall erosivity factor are obvious; it is more in line with the general law of
      NPS pollution formation in a watershed, and it can reflect the annual variability
      of NPS pollution more accurately. (2) Under the traditional and modified
      conditions, annual changes of NPS TN and TP load in four counties (districts)
      took on the similar trends from 1999 to 2008; the load emission intensity not
      only is closely related to rainfall intensity but also to the regional
      distribution of land use and other pollution sources. (3) The output structure,
      source composition, and contribution rate of NPS pollution load under the
      modified method are basically the same with the traditional method. The average
      output structure of TN from land use and rural life is about 66.5 and 17.1 %, the
      TP is about 53.8 and 32.7 %; the maximum source composition of TN (59 %) is
      farmland; the maximum source composition of TP (38.1 %) is rural life; the
      maximum contribution rates of TN and TP in Baota district are 36.26 and 39.26 %,
      respectively. Results may provide data support for NPS pollution prevention and
      control in the loess hilly and gully region and also provide scientific reference
      for the protection of ecological environment of the Loess Plateau in northern
      Shaanxi.

PMID- 25752630
TI  - An experimentally refined tool to assess the risks of the human dermal exposure
      to herbicide chlorotoluron.
AB  - Dermal absorption of the herbicide chlorotoluron was measured using ex vivo pig
      skin in Franz diffusion cells in an automated system. The steady-state flux was
      calculated, as well as the permeability coefficient, which is 0.0038 cm h(-1).
      The permeability coefficient (Kp) is a key factor when predicting human health
      risks resulting from dermal exposition to a substance. The experimental
      determination of this parameter filled data gaps regarding the dermal absorption
      of chlorotoluron. The experimental permeability coefficient was subsequently used
      to calculate the dermal absorbed dose during some exposure scenarios. Reference
      doses were revised, and screening risk assessment process was done to calculate
      the risks resulting from exposure to chlorotoluron. This refined new approach
      proved to be a useful tool for human health risk assessment in the areas with
      these herbicide applications. Graphical Abstract An experimentally refined tool
      to assess the risks of the human dermal exposure to herbicide chlorotoluron.

PMID- 25752631
TI  - Occurrence and risk assessment of selected phthalates in drinking water from
      waterworks in China.
AB  - The first nationwide survey of six phthalates (diethyl phthalate (DEP); dimethyl
      phthalate (DMP); di-n-butyl phthalate (DBP); butyl benzyl phthalate (BBP); bis(2
      ethylhexyl) phthalate (DEHP); din-octyl phthalate (DnOP)) in drinking waters from
      waterworks was conducted across seven geographical zones in China. Of the six
      target phthalates, DBP and DEHP were the highest abundant phthalates with median
      (+/- interquartile range) values of 0.18 +/- 0.47 and 0.18 +/- 0.97 MUg/L,
      respectively, but did not exceed the limit values in China's Standards for
      Drinking Water Quality. These phthalates in drinking water were generally higher
      in the northern regions of China than those in the southern and eastern regions.
      Based on the investigated concentrations, lifetime exposure risk assessment
      indicated that phthalates in drinking water did not pose carcinogenic and
      noncarcinogenic risks to Chinese residents, even under the conservative scenario
      (with 95th percentile risk). In addition, we found that DEHP contributed the
      greatest risk to the total exposure risk of all the selected phthalates and oral
      ingestion was the main exposure route for phthalates in drinking water.

PMID- 25752632
TI  - The cyanobacterium Synechocystis sp. PUPCCC 62: a potential candidate for
      biotransformation of Cr(VI) to Cr(III) in the presence of sulphate.
AB  - The cyanobacterium Synechocystis sp., an isolate from polluted water of Satluj
      river, India, was found resistant to chromium(VI) up to 200 nmol mL(-1). In this
      study, it has been demonstrated that this organism takes up Cr(VI) through a
      phosphate transporter. The organism removed 250 nmol Cr(VI), 210 nmol phosphate
      and 180 nmol sulphate mg(-1) protein from a buffer solution in 8 h. Cr(VI) uptake
      by the organism decreased to 135 nmol Cr(VI) removed per milligram protein in the
      presence of 200 nmol phosphate mL(-1), but the same concentration of sulphate did
      not affect the Cr(VI) uptake. Similarly, the presence of Cr(VI) in the solution
      affected the phosphate uptake but not sulphate uptake by the test organism. The
      kinetic studies on Cr(VI) uptake in the presence of phosphate revealed that
      phosphate and Cr(VI) acted as competitive inhibitors for one another. Phosphate
      starved cells of the organism removed more amount of Cr(VI) than the basal medium
      grown cells. The uptake of Cr(VI) as well as phosphate by the organism was
      observed to be a light-dependent process. Cinnamic acid, a phosphate transporter
      inhibitor, inhibited Cr(VI) uptake by the organism. Results clearly demonstrated
      that the test organism takes up chromate ions by phosphate transporter and not by
      the sulphate transporter. This organism is thus a potential candidate for the
      bioremediation of Cr(VI) from Cr(VI) and sulphate-laden water.

PMID- 25752634
TI  - Physiological responses of fenugreek seedlings and plants treated with cadmium.
AB  - The bioaccumulation efficiency of cadmium (Cd) by fenugreek (Trigonella foenum
      graecum) was examined using different concentrations of CdCl2. The germination
      rate was similar to control except at 10 mM Cd. However, early seedling growth
      was quite sensitive to the metal from the lowest Cd level. Accordingly, amylase
      activity was reduced substantially on treatment of seeds with 0.5, 1, and 10 mM
      Cd. Cadmium also affected various other plant growth parameters. Its accumulation
      was markedly lower in shoots as compared to roots, reducing root biomass by
      almost 50 %. Plants treated with 1 and 5 mM Cd presented chlorosis due to a
      significant reduction in chlorophyll b especially. Furthermore, at Cd
      concentrations greater than 0.1 mM, plants showed several signs of oxidative
      stress; an enhancement in root hydrogen peroxide (H2O2) level and in shoot
      malondialdehyde (MDA) content was observed. Conversely, antioxidant enzyme
      activities (superoxide dismutase (SOD), ascorbate peroxidase (APX), and catalase
      (CAT)) increased in various plant parts. Likewise, total phenolic and flavonoid
      contents reached their highest values in the 0.5 mM Cd treatment, consistent with
      their roles in quenching low concentrations of reactive oxygen species (ROS).
      Consequently, maintaining oxidant and antioxidant balance may permit fenugreek to
      hyperaccumulate Cd and allow it to be employed in extremely Cd polluted soils for
      detoxification purposes.

PMID- 25752633
TI  - Oxidative injury and antioxidant enzymes regulation in arsenic-exposed seedlings
      of four Brassica napus L. cultivars.
AB  - Environmental contamination due to arsenic (As) has become a major risk
      throughout the world; this affects plant growth and productivity. Its
      accumulation in food chain may pose a severe threat to organisms. The present
      study was carried out to observe the toxic effects of As (0, 50, 100, and 200
      MUM) on physiological and biochemical changes in four Brassica napus cultivars
      (ZS 758, Zheda 619, ZY 50, and Zheda 622). Results showed that As toxicity
      provoked a significant inhibition in growth parameters of B. napus cultivars and
      this reduction was more obvious in cultivar Zheda 622. The highest concentration
      of MDA, H2O2, and O2 (-) contents in both leaf and root tissues were observed at
      200 MUM As level, and a gradual decrease was observed at lower concentrations.
      Increasing As concentration gradually decreased chlorophyll and carotenoids
      contents. Activity of antioxidant enzymes such as SOD, CAT, APX, GR, and GSH was
      positively correlated with As treatments in all cultivars. The microscopic study
      of leaves and roots at 200 MUM As level showed the disorganization in cell
      organelles. Disturbance in the morphology of chloroplast, broken cell wall,
      increase in size, and number of starch grains and immature nucleus were found in
      leaf ultrastructures under higher concentration of As. Moreover, damaged nucleus,
      diffused cell wall, enlarged vacuoles, and a number of mitochondria were observed
      in root tip cells at 200 MUM As level. These results suggest that B. napus
      cultivars have efficient mechanism to tolerate As toxicity, as evidenced by an
      increased level of antioxidant enzymes.

PMID- 25752635
TI  - Harmful algal bloom removal and eutrophic water remediation by commercial
      nontoxic polyamine-co-polymeric ferric sulfate-modified soils.
AB  - Harmful algal bloom has posed great threat to drinking water safety worldwide. In
      this study, soils were combined with commercial nontoxic polyamine
      poly(epichlorohydrin-dimethylamine) (PN) and polymeric ferric sulfate (PFS) to
      obtain PN-PFS soils for Microcystis removal and eutrophic water remediation under
      static laboratory conditions. High pH and temperature in water could enhance the
      function of PN-PFS soil. Algal removal efficiency increased as soil particle size
      decreased or modified soil dose increased. Other pollutants or chemicals (such as
      C, P, and organic matter) in eutrophic water could participate and promote algal
      removal by PN-PFS soil; these pollutants were also flocculated. During PN-PFS
      soil application in blooming field samples, the removal efficiency of blooming
      Microcystis cells exceeded 99 %, the cyanotoxin microcystins reduced by 57 %.
      Water parameters (as TP, TN, SS, and SPC) decreased by about 90 %. CODMn, PO4-P,
      and NH4-N also sharply decreased by >45 %. DO and ORP in water improved. Netting
      and bridging effects through electrostatic attraction and complexation reaction
      could be the two key mechanisms of Microcystis flocculation and pollutant
      purification. Considering the low cost of PN-PFS soil and its nontoxic effect on
      the environment, we proposed that this soil combination could be applied to
      remove cyanobacterial bloom and remediate eutrophic water in fields.

PMID- 25752636
TI  - COST Action ES1403: new and emerging challenges and opportunities in wastewater
      reuse (NEREUS).

PMID- 25752637
TI  - Remedial effects of Potamogeton crispus L. on PAH-contaminated sediments.
AB  - In this study, the remedial effects of submerged macrophyte Potamogeton crispus
      L. on polycyclic aromatic hydrocarbon (PAH)-contaminated sediments were
      investigated. After a 54-day experiment, the dissipation ratios of phenanthrene
      and pyrene were 84.8-88.3 and 72.4-78.5% in rhizosphere sediments, which were
      significantly higher than those in non-rhizosphere sediments (54.2-66.6 and 54.7
      58.5%). The dissipation increment increased not only with increasing spiked
      concentration, but also over time, while plant uptake accounted for only a small
      portion (<6%) of the dissipation increment. Moreover, bioavailable fraction tests
      revealed that biodegradation was not controlled by the amount of bioavailable
      PAHs. For better understanding of the microbial mechanism involved, phospholipid
      fatty acid (PLFA) profiles were analyzed. Biomass of microorganisms indicated by
      the total PLFA content was higher in rhizosphere sediments than in non
      rhizosphere sediments and was related well to the dissipation ratios of the two
      PAHs. Cluster analysis showed that community structure significantly changed in
      rhizosphere sediments. Moreover, the increments of PAH dissipation in rhizosphere
      sediments had a strong positive correlation with those of polyphenol oxidase
      activities in the same media. It can be concluded that the enhanced remediation
      of PAHs by P. crispus was mainly due to the increase of microbial biomass and
      activity as well as changes of microbial community structure in sediments as a
      result of plant growth stimulation.

PMID- 25752638
TI  - Spatial and seasonal variations of methylmercury in European glass eels (Anguilla
      anguilla) in the Adour estuary (France) and relation to their migratory
      behaviour.
AB  - Overall recruitment of European glass eels (Anguilla anguilla) has decreased
      significantly since the early 1980s. Due to their long life cycle,
      benthic/demersal habits and high lipid content, eels might accumulate high
      concentrations of contaminants, but data concerning glass eels are still scarce.
      This study provides original data on methylmercury (MeHg) concentrations in glass
      eels at spatial (marine and estuarine), annual and seasonal scales. The
      relationship between MeHg concentrations in glass eels and their propensity to
      migrate up estuaries was also investigated. MeHg data were individually related
      to the eels' energetic condition which was estimated by dry weight. Glass eel
      migratory behaviour was investigated in an experimental flume and related to the
      MeHg concentration and dry weight at the individual scale. Marine and estuarine
      glass eels were caught from 2004 to 2011. There was a strong inverse correlation
      between MeHg concentrations and dry weight. MeHg concentrations increased in
      marine and estuarine glass eels from 2004 to 2009 and from 2004 to 2010,
      respectively, and then, both groups decreased in 2011. On a seasonal time scale,
      MeHg concentrations were higher at the end of the fishing season (April). MeHg
      bioaccumulation is likely to result from different sources, but the lack of
      significant differences between marine and estuarine glass eels suggests that
      direct contamination during estuarine migration is low. Other sources such as
      maternal transfer or oceanic contamination are discussed. 

PMID- 25752639
TI  - Long-term exposure of rapeseed (Brassica napus L.) to ZnO nanoparticles:
      anatomical and ultrastructural responses.
AB  - Rapid development of nanotechnology in recent years has raised concerns about
      nanoparticle (NPs) release into the environment and its adverse effects on living
      organisms. The present study is the first comprehensive report on the anatomical
      and ultrastructural changes of a variety of cells after long-term exposure of
      plant to NPs or bulk material particles (BPs). Light and electron microscopy
      revealed some anatomical and ultrastructural modifications of the different types
      of cell in the root and leaf, induced by both types of treatment. Zinc oxide
      (ZnO) BPs-induced modifications were surprisingly more than those induced by ZnO
      NPs. The modifications induced by ZnO BPs or ZnO NPs were almost similar to those
      induced by excess Zn. Zn content of the root and leaf of both ZnO NPs- and ZnO
      BPs-treated plants was severely increased, where the increase was greater in the
      plants treated with ZnO BPs. Overall, these results indicate that the
      modifications induced by ZnO particles can be attributed, at least partly, to the
      Zn(2+) dissolution by ZnO particles rather than their absorption by root and
      their subsequent effects. 

PMID- 25752640
TI  - Erythrodermic psoriasis: current and future role of biologicals.
AB  - Erythrodermic psoriasis (EP) is a severe form of psoriasis that may be associated
      with serious and sometimes fatal complications. The treatment of EP is often a
      challenge, since several factors, including treatment failure or possible
      complications, may limit favorable outcomes with traditional drugs. Recent
      evidence suggests that biological drugs, including both anti-tumor necrosis
      factor alpha agents and ustekinumab, may be useful in improving the management of
      EP. Unfortunately, since subjects with EP are usually excluded from pivotal
      trials involving biological agents, this evidence is currently dispersed in small
      case series and single case reports. In this paper, we briefly analyze
      conventional therapies for EP, before going on to critically evaluate the
      existing clinical evidence for the role of current biological drugs, namely
      infliximab, etanercept, adalimumab, and ustekinumab. Finally, we discuss the
      potential benefits that newer/developmental biological agents could bring to the
      management of EP. 

PMID- 25752641
TI  - The rising trend in allergic contact dermatitis to acrylic nail products.
AB  - Shellac is a newly available type of long-wearing nail polish, which is becoming
      increasingly popular. We describe four cases of allergic contact dermatitis (ACD)
      to acrylates found in Shellac nail products, involving three beauticians and one
      consumer who purchased the product over the internet. Increasing use of these new
      acrylic nail products means that dermatologists need to be aware of the
      possibility of ACD occurring. Testing with hydroxyethyl methacrylate alone, which
      is included in the Australian Baseline Series, is adequate for screening for
      acrylate allergy. 

PMID- 25752642
TI  - Prefrontal hypoactivation during working memory in bipolar II depression.
AB  - BACKGROUND: Patterns of abnormal neural activation have been observed during
      working memory tasks in bipolar I depression, yet the neural changes associated
      with bipolar II depression have yet to be explored. METHOD: An n-back working
      memory task was administered during a 3T functional magnetic resonance imaging
      scan in age- and gender-matched groups of 19 unmedicated, bipolar II depressed
      subjects and 19 healthy comparison subjects. Whole-brain and region-of-interest
      analyses were performed to determine regions of differential activation across
      memory-load conditions (0-, 1- and 2-back). RESULTS: Accuracy for all subjects
      decreased with higher memory load, but there was no significant group * memory
      load interaction. Random-effects analyses of memory load indicated that subjects
      with bipolar II depression exhibited significantly less activation than healthy
      subjects in left hemispheric regions of the middle frontal gyrus [Brodmann area
      (BA) 11], superior frontal gyrus (BA 10), inferior parietal lobule (BA 40),
      middle temporal gyrus (BA 39) and bilateral occipital regions. There was no
      evidence of differential activation related to increasing memory load in the
      dorsolateral prefrontal or anterior cingulate cortex. CONCLUSIONS: Bipolar II
      depression is associated with hypoactivation of the left medio-frontal and
      parietal cortex during working memory performance. Our findings suggest that
      bipolar II depression is associated with disruption of the fronto-parietal
      circuit that is engaged in working memory tasks, which is a finding reported
      across bipolar subtypes and mood states.

PMID- 25752643
TI  - Melatonin as a treatment for gastrointestinal cancer: a review.
AB  - Gastrointestinal cancer is a disease that affects the population worldwide with
      high morbidity and mortality. Melatonin, an endogenously produced molecule, may
      provide a defense against a variety of cancer types. In particular, the ability
      of melatonin to inhibit gastrointestinal cancer is substantial. In this review,
      we first clarify the relationship between the disruption of the melatonin rhythm
      and gastrointestinal cancer (based on epidemiologic surveys and animal and human
      studies) and summarize the preventive effect of melatonin on carcinogenesis.
      Thereafter, the mechanisms through which melatonin exerts its anti
      gastrointestinal cancer actions are explained, including inhibition of
      proliferation, invasion, metastasis, and angiogenesis, and promotion of apoptosis
      and cancer immunity. Moreover, we discuss the drug synergy effects and the role
      of melatonin receptors involved in the growth-inhibitory effects on
      gastrointestinal cancer. Taken together, the information compiled here serves as
      a comprehensive reference for the anti-gastrointestinal cancer actions of
      melatonin that have been identified to date and will hopefully aid in the design
      of further experimental and clinical studies and increase the awareness of
      melatonin as a therapeutic agent in cancers of the gastrointestinal tract. 

PMID- 25752644
TI  - Chronic L-DOPA induces hyperactivity, normalization of gait and dyskinetic
      behavior in MitoPark mice.
AB  - Dopamine (DA) replacement therapy continues to be the gold standard treatment for
      Parkinson's disease (PD), as it improves key motor symptoms including
      bradykinesia and gait disturbances. With time, treatment induces side effects in
      the majority of patients, known as L-DOPA-induced dyskinesia (LID), which are
      often studied in animals by the use of unilateral, toxin-induced rodent models.
      In this study, we used the progressive, genetic PD model MitoPark to specifically
      evaluate bilateral changes in motor behavior following long-term L-DOPA treatment
      at three different stages of striatal DA depletion. Besides locomotor activity,
      we assessed changes in gait with two automated gait analysis systems and the
      development of dyskinetic behavior. Long-term treatment with a moderate,
      clinically relevant dose of L-DOPA (8 mg/kg) gradually produced age-dependent
      hyperactivity in MitoPark mice. In voluntary and forced gait analyses, we show
      that MitoPark mice with severe DA depletion have distinct gait characteristics,
      which are normalized to control levels following long-term L-DOPA treatment. The
      cylinder test showed an age-dependent and gradual development of bilateral LID.
      Significant increase in striatal FosB and prodynorphin expression was found to
      accompany the behavior changes. Taken together, we report that MitoPark mice
      model both behavioral and biochemical characteristics of long-term L-DOPA
      treatment in PD patients and provide a novel, consistent and progressive animal
      model of dyskinesia to aid in the discovery and evaluation of better treatment
      options to counteract LID. 

PMID- 25752645
TI  - Qiliqiangxin inhibits angiotensin II-induced transdifferentiation of rat cardiac
      fibroblasts through suppressing interleukin-6.
AB  - Qiliqiangxin (QL), a traditional Chinese medicine, had long been used to treat
      chronic heart failure. Recent studies revealed that differentiation of cardiac
      fibroblasts (CFs) into myofibroblasts played an important role in cardiac
      remodelling and development of heart failure, however, little was known about the
      underlying mechanism and whether QL treatment being involved. This study aimed to
      investigate the effects of QL on angiotensin II (AngII)-induced CFs
      transdifferentiation. Study was performed on in vitro cultured CFs from Sprague
      Dawley rats. CFs differentiation was induced by AngII, which was attenuated by QL
      through reducing transforming growth factor-beta1 (TGF-beta1 ) and alpha-smooth
      muscle actin (alpha-SMA). Our data showed that AngII-induced IL-6 mRNA as well as
      typeI and typeIII collagens were reduced by QL. IL-6 deficiency could suppress
      TGF-beta1 and alpha-SMA, and both IL-6 siRNA and QL-mediated such effect was
      reversed by foresed expression of recombined IL-6. Increase in actin stress
      fibres reflected the process of CFs differentiation, we found stress fibres were
      enhanced after AngII stimulation, which was attenuated by pre-treating CFs with
      QL or IL-6 siRNA, and re-enhanced after rIL-6 treatment. Importantly, we showed
      that calcineurin-dependent NFAT3 nuclear translocation was essential to AngII
      mediated IL-6 transcription, QL mimicked the effect of FK506, the calcineurin
      inhibitor, on suppression of IL-6 expression and stress fibres formation.
      Collectively, our data demonstrated the negative regulation of CFs
      differentiation by QL through an IL-6 transcriptional mechanism that depends on
      inhibition of calcineurin/NFAT3 signalling. 

PMID- 25752646
TI  - Prevalence of potentially inappropriate medication use in older adults using the
      2012 Beers criteria.
AB  - OBJECTIVES: To use the most recently available population-based data to estimate
      potentially inappropriate medication (PIM) prevalence under the 2012 update of
      the Beers list of PIMs and to provide a benchmark from which to measure future
      changes. DESIGN: Retrospective cohort study using nationally representative data.
      SETTING: 2006-2010 Medical Expenditure Panel Survey (MEPS). PARTICIPANTS:
      Community-dwelling sample of U.S. older adults (N=18,475). MEASUREMENTS: The
      updated Beers criteria were operationalized, generating a "broad" PIM definition
      that incorporated form, route, or dose restrictions where clearly specified and a
      "qualified" definition that applied specific exceptions where mentioned in the
      rationale associated with each drug category. Bivariate analyses described PIM
      prevalence, comparing the two operational definitions, and examined time trends.
      RESULTS: Of older adults with prescription medications, 42.6% had at least one
      medication fill that met the broad definition, with nonsteroidal anti
      inflammatory drugs (NSAIDs) having the highest prevalence (10.9%). The rate
      declined from 45.5% in 2006-2007 to 40.8% in 2009-2010. The categories with the
      largest absolute decline were NSAIDs, selected sulfonylureas, and estrogens. PIM
      prevalence was 30.9% using the qualified definition. CONCLUSION: Despite the
      overall high use of PIMs, there has been a decline observed in recent years.
      Future studies should test the effect of educational and clinical interventions
      on changes in PIM use and outcomes. The current study results can aid in
      targeting these interventions.

PMID- 25752647
TI  - True risk of fetal/neonatal alloimmune thrombocytopenia in subsequent
      pregnancies: a prospective observational follow-up study.
AB  - OBJECTIVES: To assess neonatal platelet counts by comparing alloimmunised
      pregnancies from a Norwegian screening and intervention study with subsequent
      pregnancies from the same women. DESIGN: Prospective observational follow-up
      study. SETTING: A university hospital. POPULATION: HPA-1a immunised women from a
      large Norwegian screening study that gave birth to one or more children after the
      screening study ended (2004-2012). METHODS: Follow-up of maternal anti-HPA-1a
      antibody levels and neonatal platelet counts from the screening pregnancies were
      compared with subsequent pregnancies. None of the women received antenatal
      intravenous immunoglobulin (IVIG) treatment and neonatal platelet counts were
      therefore comparable. MAIN OUTCOME MEASURES: Change in neonatal platelet counts
      from one HPA-1a incompatible pregnancy to the next. Maternal anti-HPA-a1 antibody
      levels from one HPA-1a incompatible pregnancy to the next. RESULTS: Forty-five
      incompatible subsequent pregnancies were identified. Overall, the neonatal
      platelet count in the subsequent pregnancy was improved (18%), unchanged (52%),
      or worse (30%), compared with the corresponding screening pregnancy. There was
      one case of fetal intracranial haemorrhage (ICH) identified in the screening
      (intrauterine fetal death detected at 30 weeks of gestation) and no ICH cases
      recorded for the subsequent pregnancies. In cases where the platelet count was
      lower in the subsequent pregnancy, the maternal anti-HPA-1a antibody level was
      higher compared with the screening pregnancy. In comparison, the maternal
      antibody level was lower in subsequent pregnancies where the platelet count
      improved. CONCLUSIONS: In contrast to what is often stated, we found that the
      neonatal platelet count was increased or unchanged in the majority of subsequent
      pregnancies of HPA-1a-immunised women.

PMID- 25752649
TI  - Epicardial adipose tissue is related to coronary collateral vessel formation in
      patients with acute coronary syndrome.
AB  - OBJECTIVES: Epicardial adipose tissue (EAT) is the ectopic fat surrounding the
      heart, and it may contribute to coronary collateral vessel (CCV) formation. We
      aimed to evaluate the association of EAT with the presence of CCV in patients
      with acute coronary syndrome (ACS). DESIGN: A total of 230 patients with ACS were
      included. The CCVs were graded according to the Rentrop scoring system, and a
      Rentrop grade 0-1 was accepted as low-grade CCV group, Rentrop grade 2-3 was
      accepted as high-grade CCV group. RESULTS: According to angiography, 70 (30%)
      patients constituted the high-grade CCV group and 160 (70%) constituted the low
      grade CCV group. The high-grade CCV group had thicker EAT than the low-grade CCV
      group (6.1 +/- 1.4 vs. 5.3 +/- 1.4 mm; p = 0.001). Multivariate logistic
      regression analysis showed that presence of CCV was independently associated with
      EAT thickness, ejection fraction, presenting with ST-segment elevation myocardial
      infarction, and presence of angina on admission. EAT thickness of > 5.7 mm can
      independently predict high-grade CCV with 73% sensitivity and 69% specificity
      (area under the curve or AUC: 0.65; 95% confidence interval or CI: 0.57-0.72).
      CONCLUSIONS: EAT thickness on admission was associated with the presence of CCVs
      in patients with ACS.

PMID- 25752648
TI  - Future clinical uses of neurophysiological biomarkers to predict and monitor
      treatment response for schizophrenia.
AB  - Advances in psychiatric neuroscience have transformed our understanding of
      impaired and spared brain functions in psychotic illnesses. Despite substantial
      progress, few (if any) laboratory tests have graduated to clinics to inform
      diagnoses, guide treatments, and monitor treatment response. Providers must rely
      on careful behavioral observation and interview techniques to make inferences
      about patients' inner experiences and then secondary deductions about impacted
      neural systems. Development of more effective treatments has also been hindered
      by a lack of translational quantitative biomarkers that can span the brain
      behavior treatment knowledge gap. Here, we describe an example of a simple, low
      cost, and translatable electroencephalography (EEG) measure that offers promise
      for improving our understanding and treatment of psychotic illnesses: mismatch
      negativity (MMN). MMN is sensitive to and/or predicts response to some
      pharmacologic and nonpharmacologic interventions and accounts for substantial
      portions of variance in clinical, cognitive, and psychosocial functioning in
      schizophrenia (SZ). This measure has recently been validated for use in large
      scale multisite clinical studies of SZ. Finally, MMN greatly improves our ability
      to forecast which individuals at high clinical risk actually develop a psychotic
      illness. These attributes suggest that MMN can contribute to personalized
      biomarker-guided treatment strategies aimed at ameliorating or even preventing
      the onset of psychosis. 

PMID- 25752651
TI  - A Combination Therapy of 17beta-Estradiol and Memantine Is More Neuroprotective
      Than Monotherapies in an Organotypic Brain Slice Culture Model of Traumatic Brain
      Injury.
AB  - Combination therapies are a promising therapeutic option for traumatic brain
      injury (TBI) owing to the clinical failure of monotherapy treatments, such as
      progesterone. Organotypic hippocampal slice cultures (OHSCs) from Sprague-Dawley
      rats were subjected to an in vitro TBI, and the neuroprotective effects of 17beta
      estradiol (E2) or memantine (MEM) monotherapies were quantified. Several
      combination treatments at different concentrations of both drugs were tested,
      with 100 pM of E2 and 10 MUM of MEM statistically and significantly reducing cell
      death over either monotherapy when administered immediately after injury. This
      combination was also significantly neuroprotective when administered 1 h
      postinjury, possibly supporting future in vivo studies. Further, we hypothesized
      that this synergy could be the result of MEM blocking a potentially deleterious
      effect of E2, specifically E2 enhancement of N-methyl-D-aspartate (NMDA)
      currents. Evoked electrophysiological responses in OHSCs were potentiated by E2
      treatment, whereas this potentiation was significantly reduced by MEM. In
      conclusion, a combination therapy of E2 and memantine was significantly more
      neuroprotective than both monotherapy treatments, and this synergy may be the
      result of MEM blocking a deleterious E2-mediated enhancement of NMDA receptors.

PMID- 25752650
TI  - The Use of Calcimimetics for the Treatment of Secondary Hyperparathyroidism: A 10
      Year Evidence Review.
AB  - Until the discovery of calcimimetics, the management of secondary
      hyperparathyroidism (SHPT) relied exclusively on treatment with phosphate
      binders, vitamin D derivatives or surgical parathyroidectomy with limited
      success. The therapeutic use of calcimimetic agents, together with a better
      understanding of the pivotal role of the calcium-sensing receptor (CaSR) in the
      physiological regulation of parathyroid gland function, substantially advanced
      the management of hyperparathyroidism in dialysis practice. Calcimimetics bind
      selectively to the CaSR receptor in parathyroid tissue and enhance the inhibitory
      effect of extracellular calcium ions on parathyroid hormone (PTH) secretion,
      thereby reducing PTH levels even when serum calcium concentrations are normal or
      low. The availability of calcimimetic agents for clinical use has opened a new
      era in the management of patients with SHPT. Indeed, calcimimetic compounds have
      been shown to reduce PTH levels and to lower serum calcium concentrations in all
      forms of hyperparathyroidism, including primary hyperparathyroidism (PHPT) and
      parathyroid carcinoma. Such findings underscore the critical importance of the
      CaSR as a therapeutic target in this family of clinical disorders. New
      calcimimetic agents are being developed that have the potential to offer improved
      efficacy and safety compared with currently available calcimimetic compounds. 

PMID- 25752652
TI  - Reversible Late Thoracic Myelopathy and Neurostimulation Tolerance Caused by
      Fibrous Scar Tissue Formation Around the Spinal Cord Stimulation Electrode.
AB  - OBJECTIVE: Spinal cord stimulation has now been used for four decades and has
      become an established treatment for neuropathic pain. Spinal cord compression by
      formation of excessive fibrous tissue at the level of an epidural
      neurostimulation electrode is a rare, delayed, but serious complication of
      neuromodulation for chronic neuropathic pain that may appear at various timings
      after the initial surgery, but is usually preceded by progressive tolerance and
      fading of the pain-relieving effect of the neurostimulation. METHODS: We report
      one patient treated by neuromodulation with percutaneous lead between 1998 and
      2001, then by a larger surgical lead since 2001. He started presenting with
      clinical signs of spinal cord compression, along with progressive fading of the
      antalgic effect of the stimulation five years later, finally leading to surgery
      in 2013. RESULTS: The microsurgical removal of fibrous tissue under the electrode
      allowed both the decompression of the spinal cord and the return of efficient
      pain control, while leaving the electrode at the same place. CONCLUSION: Careful
      surgical removal of the fibrous tissue can be performed to allow decompression of
      the spinal cord and may help to obtain a more efficient pain management. As large
      surgical electrodes could be specifically associated with compressive scar tissue
      formation, they should therefore be considered as a second line of treatment
      after percutaneous leads.

PMID- 25752654
TI  - The timing of autologous stem cell transplantation and the prognostic factors
      affecting the prognosis in children with relapsed Hodgkin lymphoma.
AB  - Although ASCT is used as a standard treatment following second remission for
      adults in oncology practice, data are lacking for relapsed childhood HL.
      Therefore, we evaluated the exact timing of the ASCT treatment, as well as
      factors affecting the prognosis in children with relapsed HL who underwent ASCT.
      Patients were divided into two groups (Group 1: ASCT after second remission [n =
      6], Group 2: ASCT after >2 remissions [n = 3]). Overall, DFS rate was 64.8% at 24
      months after ASCT. In Group 1, post-transplant DFS and OS were 83.3% and 75%,
      respectively, and the post-transplant response without event rate was 5/6
      (83.3%). However, in Group 2 this was 1/3 (33.3%). Nonetheless, the timing of
      ASCT was not a significant prognostic factor for DFS and OS in univariate
      analyses (p = 0.21 and p = 0.73, respectively). Median follow-up time was 21
      months after transplant, and DFS and OS were 62.5% and 75% in early relapse group
      (n = 6) at 24 months. DFS and OS were both 66.7% in late relapse (n = 3). In
      addition, response rates of ASCT without event were 66.7% for both early and late
      relapse groups. Relapse types (early: 3-12 months, late: >12 months) was not a
      significant prognostic factor for DFS and OS in univariate analyses (p = 0.96 and
      p = 0.92). While we found ASCT to be a useful treatment following second
      remission, it does not demonstrate better success in early relapse cases, when
      compared to late relapse cases. Therefore, after second remission for relapsed
      HL, ASCT is advisable regardless of the time of relapse.

PMID- 25752655
TI  - Gas phase selective hydrogenation over oxide supported Ni-Au.
AB  - The chemoselective continuous gas phase (T = 573 K; P = 1 atm) hydrogenation of
      nitroarenes (p-chloronitrobenzene (p-CNB) and m-dinitrobenzene (m-DNB)) has been
      investigated over a series of oxide (Al2O3 and TiO2) supported Au and Ni-Au (1 :
      10 mol ratio; 0.1-1 mol% Au) catalysts. Monometallic supported Au with mean
      particle size 3-9 nm promoted exclusive formation of p-chloroaniline (p-CAN) and
      m-nitroaniline (m-NAN). Selective hydrogenation rate was higher over smaller Au
      particles and can be attributed to increased surface hydrogen (from TPD
      measurements) at higher metal dispersion. (S)TEM analysis has confirmed an
      equivalent metal particle size for the supported bimetallics at the same Au
      loading where TPR indicates Ni-Au interaction and EDX surface mapping established
      Ni in close proximity to Au on isolated nanoparticles with a composition (Au/Ni)
      close to the bulk value (= 10). Increased spillover hydrogen due to the
      incorporation of Ni in the bimetallics resulted in elevated -NO2 group reduction
      rate. Full selectivity to p-CAN was maintained over all the bimetallic catalysts.
      Conversion of m-DNB over the lower loaded Ni-Au/Al2O3 generated m-NAN as sole
      product. An increase in Ni content (0.01 -> 0.1 mol%) or a switch from Al2O3 to
      TiO2 as support resulted in full -NO2 reduction (to m-phenylenediamine). Our
      results demonstrate the viability of Ni-promotion of Au in the continuous
      production of functionalised anilines.

PMID- 25752656
TI  - Working conditions and leisure-time physical activity among waged workers in
      South Korea: A cross-sectional study.
AB  - OBJECTIVES: Although waged workers' working conditions have notably diversified
      in South Korea, there is little research addressing this issue. This study
      explores the relationship between working conditions and engagement in leisure
      time physical activities (LTPA) among waged workers in South Korea. METHODS: Data
      from 19- to 64-year-old waged workers (men=2,562, women=1,627) from the 11th wave
      of the Korean Income and Labor Panel Study were included in this study. Multiple
      logistic regression analyses were conducted to assess the association between
      LTPA and working conditions by gender. RESULTS: More than 75% of employed persons
      did not participate in any type of LTPA. For male workers, those in manual,
      precarious, overtime, and non-shift positions were less likely to engage in LTPA,
      while for female workers, only manual and overtime work positions were
      significant factors influencing a low level of LTPA. CONCLUSIONS: Some negative
      work-related factors were associated with low LTPA, especially for male workers.
      Further studies should be conducted to clarify the pathways and barriers
      precluding engagement in LTPA due to work-related factors.

PMID- 25752657
TI  - Analysis of salivary cortisol levels to determine the association between
      depression level and differences in circadian rhythms of shift-working nurses.
AB  - OBJECTIVE: The aim of this study was to clarify whether there are differences in
      the circadian rhythms of shift-working nurses by assessing depression, fatigue
      and salivary cortisol levels. METHODS: Forty nurses working in a two-shift system
      at "Hospital A", Fukuoka City, Japan, used a self-rated depression scale (SDS) to
      assess their depression levels. Fatigue levels were measured with the visual
      analogue scale for fatigue (VAS-F); saliva was collected before and during shifts
      for three days. Results were analyzed with analysis of variance (ANOVA). RESULTS:
      Thirty-six valid records were obtained, and subjects were classified according to
      SDS scores into a normal group (NG), moderate group (MG) and severe group (SG).
      There were no significant differences in the day shift salivary cortisol values
      of the three groups. However, the night shift salivary cortisol value for the SG
      was 0.132 ug/dl at 16:00, before starting the shift, and decreased to 0.036 ug/dl
      at 20:00. It increased slightly up to 0.057 ug/dl by 24:00 and formed a peak
      between 5:00 and 7:00, with the levels being 0.322 ug/dl and 0.305 ug/dl
      respectively. Meanwhile, the NG cortisol value was 0.154 ug/dl before the shift,
      decreased to 0.034 ug/dl by 20:00, slightly increased up to 0.093 ug/dl by 5:00
      and presented its peak value, 0.253 ug/dl, at 7:00 next morning. CONCLUSIONS: SG
      nurses presented significantly increased salivary cortisol levels early in the
      morning during night shifts, showing a phase deviation in the circadian rhythm.
      Because subjective fatigue levels did not differ with time, SG nurses should
      understand and deal with physical changes in the early morning. This approach may
      reduce medical accidents and malpractice in the early morning.

PMID- 25752658
TI  - Evaluation of DNA damage in lymphocytes of radiology personnel by comet assay.
AB  - OBJECTIVES: The importance of X-rays as a diagnostic medical tool cannot be
      denied. However, continuous exposure to X-rays can cause DNA damage. This study
      aimed to use the comet assay technique to investigate the level of DNA damage in
      lymphocytes due to X-rays in occupationally exposed personnel. METHODS: Blood
      samples were collected from 74 exposed and 70 control subjects for analysis. A
      total of 100 randomly captured cells from each slide were examined using an
      epifluorescent microscope. The comets were analyzed by a visual scoring method
      according to comet tail length. RESULTS: The results indicated a significant
      increase (p<0.05) in DNA damage in X-rays technicians (129.8 +/- 17.2) as
      compared with the control group (53.0 +/- 25.0). A significant increase (p<0.02)
      in DNA damage was also observed with an increase in exposure duration of
      technicians because of their service length. CONCLUSIONS: The present study
      suggests that the exposed radiology personnel should carefully comply with
      radiation protection procedures such as wearing of lead apron during diagnostic
      procedures and minimize radiation exposure where possible to avoid potential
      genotoxic effects due to X-rays.

PMID- 25752659
TI  - Is suicidal ideation linked to working hours and shift work in Korea?
AB  - OBJECTIVE: This study attempted to use the community health survey (CHS) to
      identify the effect of long working hours (long WHs) and night/shift work on
      suicidal ideation among the employed population of Korea. METHODS: This study
      used data from 67,471 subjects who were administered the 2008 CHS which obtained
      information regarding sociodemographic characteristics, health behaviors and
      working environment, using structured questionnaires and personal interviews. We
      adopted multiple logistic regression models for gender and employment
      stratification. RESULTS: Among male employees, suicidal ideation was
      significantly associated with only moderately long WHs (51-60 hours), after
      controlling covariates (adjusted odds ratio [aOR], 1.30; 95% confidence interval
      [95%CI], 1.07 to 1.57). Self-employed/male employer populations had higher
      suicidal ideation when they had moderately long WHs (aOR, 1.23; 95%CI, 1.01 to
      1.50) and very long WHs (over 60 hours) (aOR, 1.31; 95%CI, 1.08 to 1.59). Among
      the female population, suicidal ideation was significantly association with
      moderately long WHs in the employee group (aOR, 1.31; 95%CI, 1.08 to 1.58) and
      moderately (aOR, 1.35; 95%CI, 1.08 to 1.69) and very (aOR, 1.33; 95%CI, 1.07 to
      1.65) long WHs in the self-employed/employer group. Shift work was a significant
      predictor only in the female population in the employee groups (aOR, 1.45; 95%CI,
      1.23 to 1.70). CONCLUSIONS: Long WHs and shift work were associated with suicidal
      ideation when taking into account gender and employment differences. The harmful
      effects of exceptionally long WHs in Korea, among other Organization for Economic
      Co-operation and Development (OECD) countries, raise concerns about public and
      occupational health. To address the issue of long WHs, labor policies that reduce
      maximum working hours and facilitate job stability are needed.

PMID- 25752660
TI  - Screening of dry eye disease in visual display terminal workers during
      occupational health examinations: The Moriguchi study.
AB  - PURPOSE: The aim of this study was to estimate the prevalence of dry eye disease
      (DED) in Japanese visual display terminal (VDT) workers and identify simple
      methods for screening DED during occupational health examinations. METHODS: This
      study involved 369 (331 men and 38 women; mean age, 44.4 [8.8] years) workers
      engaged in PC development with approximately 6 hours of VDT use daily. The
      participants completed questionnaires on dry eye and physical symptoms affecting
      QoL, and their ability to keep their eyes open for 10 seconds was tested for DED
      screening. They also underwent assessment of conjunctival and corneal vital
      staining with lissamine green and fluorescein, measurement of tear film breakup
      time, and Schirmer's test for DED diagnosis. Sensitivity, specificity, and
      positive predictive value of the screening methods were assessed. RESULTS: The
      DED group included 218 (definite, 14; probable, 204) participants. They had
      markedly high frequencies of 11 dry eye symptoms, especially ocular fatigue (OR,
      17.1; 95% CI, 9.9 to 29.7) and dry sensation (OR, 8.2; 95% CI, 3.6 to 18.4), and
      were more often unable to keep their eyes open for 10 s. With either ocular
      fatigue or dry sensation as the cutoff criterion, the sensitivity, specificity,
      and positive predictive value were 89.9, 66.9, and 79.7%, respectively.
      CONCLUSIONS: Approximately 60% of the VDT workers were diagnosed with DED on the
      basis of diverse eye symptoms affecting their ability to work. The dry eye
      symptom questionnaire and 10-s eye-opening test are simple, noninvasive, and
      inexpensive methods for screening DED during occupational health examinations.

PMID- 25752662
TI  - Lewis acid behavior of SF4 : synthesis, characterization, and computational study
      of adducts of SF4 with pyridine and pyridine derivatives.
AB  - Sulfur tetrafluoride was shown to act as a Lewis acid towards organic nitrogen
      bases, such as pyridine, 2,6-dimethylpyridine, 4-methylpyridine, and 4
      dimethylaminopyridine. The SF4 ?NC5 H5 , SF4 ?2,6-NC5 H3 (CH3 )2 , SF4 ?4-NC5 H4
      (CH3 ), and SF4 ?4-NC5 H4 N(CH3 )2 adducts can be isolated as solids that are
      stable below -45  degrees C. The Lewis acid-base adducts were characterized by
      low-temperature Raman spectroscopy and the vibrational bands were fully assigned
      with the aid of density functional theory (DFT) calculations. The electronic
      structures obtained from the DFT calculations were analyzed by the quantum theory
      of atoms in molecules (QTAIM). The crystal structures of SF4 ?NC5 H5 , SF4 ?4-NC5
      H4 (CH3 ), and SF4 ?4-NC5 H4 N(CH3 )2 revealed weak S?N dative bonds with
      nitrogen coordinating in the equatorial position of SF4 . Based on the QTAIM
      analysis, the non-bonded valence shell charge concentration on sulfur, which
      represents the lone pair, is only slightly distorted by the weak dative S?N bond.
      No evidence for adducts between quinoline or isoquinoline with SF4 was found by
      low-temperature Raman spectroscopy. 

PMID- 25752661
TI  - Charge-neutralization effect of the tail regions on the histone H2A/H2B dimer
      structure.
AB  - It is well known that various modifications of histone tails play important roles
      in the regulation of transcription initiation. In this study, some lysine (Lys)
      and arginine (Arg) residues were acetylated and deiminated, respectively, in the
      histone H2A/H2B dimer, and charge-neutralization effects on the dimer structure
      were studied by native mass spectrometry. Given that both acetylation and
      deimination neutralize the positive charges of basic amino acid residues, it had
      been expected that these modifications would correspondingly affect the gas-phase
      behavior of the histone H2A/H2B dimer. Contrary to this expectation, it was found
      that Arg deimination led to greater difficulty of dissociation of the dimer by
      gas-phase collision, whereas acetylation of Lys residues did not cause such a
      drastic change in the dimer stability. In contrast, ion mobility-mass
      spectrometry (IM-MS) experiments showed that arrival times in the mobility cell
      both of acetylated and of deiminated dimer ions changed little from those of the
      unmodified dimer ions, indicating that the sizes of the dimer ions did not change
      by modification. Charge neutralization of Arg, basicity of which is higher than
      Lys, might have triggered some alteration of the dimer structure that cannot be
      found in IM-MS but can be detected by collision in the gas phase. 

PMID- 25752663
TI  - In vivo reflectance confocal microscopy of equivocal melanocytic lesions detected
      by digital dermoscopy follow-up.
AB  - BACKGROUND: Digital follow-up is a useful method for the detection of melanoma in
      atypical mole syndrome patients. The combination of digital follow-up (DFU) and
      reflectance confocal microscopy (RCM) could be useful to increase the accuracy in
      the classification of equivocal lesions in atypical mole syndrome patients.
      OBJECTIVES: To assess the impact of RCM analysis on sensitivity and specificity
      of digital follow-up in a high-risk melanoma setting. METHODS: Retrospective
      study with dermoscopy and RCM of consecutive equivocal atypical melanocytic
      lesions exhibiting changes in digital dermoscopy in a referral centre. RESULTS:
      Sixty-four lesions from 51 patients were included. Thirteen changing lesions
      (20.3%) corresponded to eight melanomas in situ and five invasive melanomas with
      Breslow less than 1 mm. Fifty-one lesions corresponded to melanocytic naevus with
      variable atypia. Total dermoscopy scores were not different between naevus and
      melanoma neither in the baseline (mean 5.06 and 5.24; P = 0.37) nor in the follow
      up dermoscopic control (mean 5.44 and 5.55; P = 0.37). The only significant
      dermoscopic feature associated with melanoma in multivariate analysis was the
      presence of streaks after follow-up (P = 0.027; OR = 3.6; CI 1.50-8.70). The
      confocal microscopy evaluation (by means both the Modena and Barcelona methods)
      showed a sensitivity and specificity for the diagnosis of melanoma of 100% and
      69% respectively. Based on our experience, the combination of RCM and DFU could
      have avoided 35 of 51 nevi excised. CONCLUSIONS: Reflectance confocal microscopy
      evaluation of equivocal lesions detected by DFU improved the accuracy in the
      detection of melanoma. The combination of dermoscopy, DFU and confocal microscopy
      in equivocal lesions can be useful to dramatically reduce the number of excisions
      of benign lesions in atypical mole syndrome patients.

PMID- 25752664
TI  - Asymptomatic bilateral palatal swelling as a rare initial presentation of a
      rapidly progressive and fatal disease in an elderly man.

PMID- 25752665
TI  - Memantine overdose in a non-demented older adult.

PMID- 25752666
TI  - Factors associated with the burden of caregivers of patients with dementia.

PMID- 25752667
TI  - Touch on the acupoint of Shinchuu of Alzheimer's disease patients.

PMID- 25752669
TI  - Transcultural issues on the assessment of executive functions and processing
      speed in older adults with low formal education: Usefulness of the Five Digits
      Test in the assessment of dementia.

PMID- 25752668
TI  - Lactobacillus bifidus and pathogenic Escherichia coli in geriatric patients.

PMID- 25752670
TI  - Harmonic focus in thyroidectomy for substernal goiter.
AB  - OBJECTIVES: No previous prospective study has evaluated harmonic scalpel in
      thyroidectomy for substernal goiter. The objective of this study was to evaluate
      the use of harmonic scalpel (FOCUS shear, Ethicon Endo-Surgery) in thyroidectomy
      for substernal goiter for blood loss, operative time, hospital stay and
      complications. MATERIALS AND METHODS: Prospective non-randomised study of 242
      consecutive patients with substernal goiter out of 2258 patients (11%) who
      underwent thyroidectomy. A total of 121 patients had thyroidectomy performed with
      bipolar electrocoagulation and knot-tying techniques and 121 patients had
      harmonic scalpel thyroidectomy. RESULTS: The use of harmonic scalpel was
      associated with significant reduction in intraoperative blood loss (50 vs. 100mL,
      p=0.001), postoperative haemorrhage (4% vs. 12%, p=0.03) and length of hospital
      stay (2 vs. 3 days, p=0.001). The mean operative time was significantly longer in
      the harmonic group. CONCLUSION: Harmonic scalpel is a safe tool for thyroidectomy
      for substernal goiter. Its utilisation is associated with reduced blood loss,
      lower incidence of postoperative haemorrhage and shorter hospital stay.

PMID- 25752671
TI  - Comparison of ultrashort echo time sequences for MRI of an ancient mummified
      human hand.
AB  - PURPOSE: To compare the three different short-echo time (TE) pulse sequences
      ultrashort echo time (UTE), point-wise encoding time reduction with radial
      acquisition (PETRA), and single point imaging (SPI) for MRI of ancient remains.
      METHODS: MRI of mummies is challenging due to the extremely low water content and
      the very short transverse relaxation times T2 *. To overcome the signal loss
      associated with the short T2 *, three pulse sequences with very short TEs were
      compared. MR images of an ancient mummified human hand were acquired at field
      strengths of 1.5 Tesla (T) and 3T using home-made solenoid Tx/Rx radiofrequency
      (RF) coils. RESULTS: In all MR images, tissues could be differentiated and
      anatomical structures such as bones and tendons were clearly identified. Skin
      with embalming resin was hyperintense in MRI, whereas it appeared iso-intense in
      computed tomography. PETRA has the highest signal to noise ratio. With UTE, short
      scan times and a homogeneous RF excitation can be achieved, and blurring is less
      pronounced than with PETRA. SPI shows no blurring artifacts; however, it requires
      long scan times. CONCLUSION: This work provided an initial analysis for the
      optimization of imaging protocols for paleoradiology studies with MRI, and,
      ultimately, for MRI of tissue with extremely short T2 *.

PMID- 25752672
TI  - Novel vascular endothelial growth factor blocker improves cellular viability and
      reduces hypobaric hypoxia-induced vascular leakage and oedema in rat brain.
AB  - Vascular endothelial growth factor (VEGF) is an important cerebral angiogenic and
      permeability factor under hypoxia. There is a need to find effective molecules
      that may ameliorate hypoxia-induced cerebral oedema. In silico identification of
      novel candidate molecules that block VEGF-A site were identified and validated
      with a Ramachandran plot. The active site residues of VEGF-A were detected by
      Pocketfinder, CASTp, and DogSiteScorer. Based on in silico data, three VEGF-A
      blocker (VAB) candidate molecules (VAB1, VAB2, and VAB3) were checked for
      improvement in cellular viability and regulation of VEGF levels in N2a cells
      under hypoxia (0.5% O2 ). Additionally, the best candidate molecule's efficacy
      was assessed in male Sprague-Dawley rats for its ameliorative effect on cerebral
      oedema and vascular leakage under hypobaric hypoxia 7260 m. All experimental
      results were compared with the commercially available VEGF blocker sunitinib.
      Vascular endothelial growth factor-A blocker 1 was found most effective in
      increasing cellular viability and maintaining normal VEGF levels under hypoxia
      (0.5% oxygen) in N2a cells. Vascular endothelial growth factor-A blocker 1
      effectively restored VEGF levels, decreased cerebral oedema, and reduced vascular
      leakage under hypobaric hypoxia when compared to sunitinib-treated rats. Vascular
      endothelial growth factor-A blocker 1 may be a promising candidate molecule for
      ameliorating hypobaric hypoxia-induced vasogenic oedema by regulating VEGF
      levels.

PMID- 25752673
TI  - Peritoneal metastases: challenges for the surgeon.
AB  - Peritoneal surface malignancies (PSM) include peritoneal metastases from
      gastrointestinal and gynecological tumor and rare primary peritoneal
      malignancies. PSM have been historically considered as end-stage metastatic
      conditions only amenable to palliative options. Only in recent years, better
      knowledge of their natural history and pattern of disease-progression has evolved
      into the concept that PSM represent a local-regional disease stage. A novel
      treatment approach aiming at definitive disease eradication combines aggressive
      cytoreductive surgery (CRS) and perioperative local-regional chemotherapy, either
      in the form of hyperthermic intraperitoneal chemotherapy (HIPEC), or normothermic
      early postoperative chemotherapy. Such a combined treatment approach has
      reportedly resulted in a survival improvement over historical controls, and it is
      gaining an increasing acceptance as standard of care for selected patients with
      PSM. This article reviews the most recent literature data on the surgical and
      comprehensive management of PSM. Epidemiology and natural history of the
      different disease entities are briefly discussed. Cytoreductive surgical
      procedures and intraperitoneal chemotherapy administration techniques are
      described, focusing on the technical variants adopted in our institution.
      Indications for combined treatment, and outcomes following CRS/HIPEC, are
      addressed, including peritoneal metastases from appendiceal tumors (pseudomyxoma
      peritonei), colorectal cancer, gastric cancer, epithelial ovarian cancer, and
      rare primary peritoneum based neoplasms, such as diffuse malignant peritoneal
      mesothelioma, and primary peritoneal (extra-ovarian) serous papillary carcinoma. 

PMID- 25752674
TI  - Linear alkane C-C bond chemistry mediated by metal surfaces.
AB  - Linear alkanes undergo different C-C bond chemistry (coupling or dissociation)
      thermally activated on anisotropic metal surfaces depending on the choice of the
      substrate material. Owing to the one-dimensional geometrical constraint,
      selective dehydrogenation and C-C coupling (polymerization) of linear alkanes
      take place on Au(110) surfaces with missing-row reconstruction. However, the case
      is dramatically different on Pt(110) surfaces, which exhibit similar
      reconstruction as Au(110). Instead of dehydrogenative polymerization, alkanes
      tend to dehydrogenative pyrolysis, resulting in hydrocarbon fragments. Density
      functional theory calculations reveal that dehydrogenation of alkanes on Au(110)
      surfaces is an endothermic process, but further C-C coupling between alkyl
      intermediates is exothermic. On the contrary, due to the much stronger C-Pt
      bonds, dehydrogenation on Pt(110) surfaces is energetically favorable, resulting
      in multiple hydrogen loss followed by C-C bond dissociation.

PMID- 25752675
TI  - Comparative toxicity of silicon dioxide, silver and iron oxide nanoparticles
      after repeated oral administration to rats.
AB  - Although silicon dioxide (SiO2), silver (Ag) and iron oxide (Fe2O3) nanoparticles
      are widely used in diverse applications from food to biomedicine, in vivo
      toxicities of these nanoparticles exposed via the oral route remain highly
      controversial. To examine the systemic toxicity of these nanoparticles, well
      dispersed nanoparticles were orally administered to Sprague-Dawley rats daily
      over a 13-week period. Based on the results of an acute toxicity and a 14-day
      repeated toxicity study, 975.9, 1030.5 and 1000 mg kg(-1) were selected as the
      highest dose of the SiO2 , Ag and Fe2O3 nanoparticles, respectively, for the 13
      week repeated oral toxicity study. The SiO2 and Fe2O3 nanoparticles did not
      induce dose-related changes in a number of parameters associated with the
      systemic toxicity up to 975.9 and 1000 mg kg(-1) , respectively, whereas the Ag
      nanoparticles resulted in increases in serum alkaline phosphatase and calcium as
      well as lymphocyte infiltration in liver and kidney, raising the possibility of
      liver and kidney toxicity induced by the Ag nanoparticles. Compared with the SiO2
      and Fe2O3 nanoparticles showing no systemic distribution in all tissues tested,
      the Ag concentration in sampled blood and organs in the Ag nanoparticle-treated
      group significantly increased with a positive and/or dose-related trend, meaning
      that the systemic toxicity of the Ag nanoparticles, including liver and kidney
      toxicity, might be explained by extensive systemic distribution of Ag originating
      from the Ag nanoparticles. Our current results suggest that further study is
      required to identify that Ag detected outside the gastrointestinal tract were
      indeed a nanoparticle form or ionized form.

PMID- 25752676
TI  - Orangutans (Pongo spp.) have deeper, more efficient sleep than baboons (Papio
      papio) in captivity.
AB  - The nightly construction of arboreal sleeping platforms or "nests" has been
      observed among every great ape population studied to date. However, this behavior
      has never been reported in any other nonhuman primate and comparisons between ape
      and monkey sleep illuminate the link between sleeping substrates, positional
      behavior, and sleep efficiency. Here, we compare sleep depth and efficiency and
      night-time positional behavior between a large-bodied cercopithecoid (Papio
      papio) and a large-bodied hominoid (Pongo spp.) at the Indianapolis Zoo. We used
      infrared videography to assess nightly sleep and awake behavioral states, gross
      body movements, and postures in baboons (N = 45 nights) and orangutans (N = 128
      nights). We calculated the total waking time, total sleep time, sleep
      fragmentation (the number of brief awakenings >=2 min/h), sleep motor activity
      (number of motor activity bouts per hour), sleep efficiency (sleep duration/time
      in bed), and percentage of time spent in each posture. By every measure,
      orangutans experienced overall deeper, more efficient sleep. Baboons were more
      likely to sleep in guarded, upright positions (weight bearing on their ischial
      callosities) and never opted to use additional materials to augment sleep
      environments, whereas orangutans slept in insouciant, relaxed positions on
      constructed sleeping materials. Our results suggest that relaxed sleeping
      postures may have been enabled by sleeping platforms as a behavioral facilitator
      to sleep, which could have allowed for greater sleep depth and next-day cognitive
      capacities in both great apes and hominins.

PMID- 25752677
TI  - Feasibility of the internal mammary lymph node flap as a vascularized lymph node
      transfer: A cadaveric dissection study.
AB  - BACKGROUND: We performed cadaveric dissections to examine the feasibility of an
      internal mammary-based lymph node flap as a donor site for vascularized lymph
      node transfer. METHODS: Internal mammary vessels and adjacent nodes were
      dissected in ten fresh cadaver specimens. Surgeon inspection and palpation
      identified the number of nodes in the specimen. Specimens were examined macro-
      and microscopically by a pathologist for correlation of lymph node counts. Kappa
      statistic correlated surgeon- and pathologist-reported node counts. RESULTS:
      Surgeon- and pathologist-reported node counts were moderately correlated (kappa
      0.57). Inspection and palpation correctly predicted node presence or absence in
      80% of specimens. Sixty percent of flaps contained between 1 and 3 nodes, with a
      mean of 2.0 nodes when nodes were present. CONCLUSIONS: Inspection and palpation
      predicts the presence or absence of nodes in 80% of flaps. Nodes were present in
      60% of internal mammary-based flaps, and one to three nodes can be transferred.
      (c) 2015 Wiley Periodicals, Inc. Microsurgery 36:485-490, 2016.

PMID- 25752681
TI  - Systems Chemo-Biology and Transcriptomic Meta-Analysis Reveal the Molecular Roles
      of Bioactive Lipids in Cardiomyocyte Differentiation.
AB  - Lipids, which are essential constituents of biological membranes, play structural
      and functional roles in the cell. In recent years, certain lipids have been
      identified as regulatory signaling molecules and have been termed "bioactive
      lipids". Subsequently, the importance of bioactive lipids in stem cell
      differentiation and cardiogenesis has gained increasing recognition. Therefore,
      the aim of this study was to identify the biological processes underlying murine
      cardiac differentiation and the mechanisms by which bioactive lipids affect these
      processes. For this purpose, a transcriptomic meta-analysis of microarray and RNA
      seq data from murine stem cells undergoing cardiogenic differentiation was
      performed. The differentially expressed genes identified via this meta-analysis,
      as well as bioactive lipids, were evaluated using systems chemo-biology tools.
      These data indicated that bioactive lipids are associated with the regulation of
      cell motility, cell adhesion, cytoskeletal rearrangement, and gene expression.
      Moreover, bioactive lipids integrate the signaling pathways involved in cell
      migration, the secretion and remodeling of extracellular matrix components, and
      the establishment of the cardiac phenotype. In conclusion, this study provides
      new insights into the contribution of bioactive lipids to the induction of
      cellular responses to various stimuli, which may originate from the extracellular
      environment and morphogens, and the manner in which this contribution directly
      affects murine heart morphogenesis.

PMID- 25752680
TI  - Effects of climate extremes on the terrestrial carbon cycle: concepts, processes
      and potential future impacts.
AB  - Extreme droughts, heat waves, frosts, precipitation, wind storms and other
      climate extremes may impact the structure, composition and functioning of
      terrestrial ecosystems, and thus carbon cycling and its feedbacks to the climate
      system. Yet, the interconnected avenues through which climate extremes drive
      ecological and physiological processes and alter the carbon balance are poorly
      understood. Here, we review the literature on carbon cycle relevant responses of
      ecosystems to extreme climatic events. Given that impacts of climate extremes are
      considered disturbances, we assume the respective general disturbance-induced
      mechanisms and processes to also operate in an extreme context. The paucity of
      well-defined studies currently renders a quantitative meta-analysis impossible,
      but permits us to develop a deductive framework for identifying the main
      mechanisms (and coupling thereof) through which climate extremes may act on the
      carbon cycle. We find that ecosystem responses can exceed the duration of the
      climate impacts via lagged effects on the carbon cycle. The expected regional
      impacts of future climate extremes will depend on changes in the probability and
      severity of their occurrence, on the compound effects and timing of different
      climate extremes, and on the vulnerability of each land-cover type modulated by
      management. Although processes and sensitivities differ among biomes, based on
      expert opinion, we expect forests to exhibit the largest net effect of extremes
      due to their large carbon pools and fluxes, potentially large indirect and lagged
      impacts, and long recovery time to regain previous stocks. At the global scale,
      we presume that droughts have the strongest and most widespread effects on
      terrestrial carbon cycling. Comparing impacts of climate extremes identified via
      remote sensing vs. ground-based observational case studies reveals that many
      regions in the (sub-)tropics are understudied. Hence, regional investigations are
      needed to allow a global upscaling of the impacts of climate extremes on global
      carbon-climate feedbacks. 

PMID- 25752683
TI  - Pressure-assisted introduction of urine samples into a short capillary for
      electrophoretic separation with contactless conductivity and UV spectrometry
      detection.
AB  - A computer-controlled hydrodynamic sample introduction method has been proposed
      for short-capillary electrophoresis. In the method, the BGE flushes sample from
      the loop of a six-way sampling valve and is carried to the injection end of the
      capillary. A short pressure impulse is generated in the electrolyte stream at the
      time when the sample zone is at the capillary, leading to injection of the sample
      into the capillary. Then the electrolyte flow is stopped and the separation
      voltage is turned on. This way of sample introduction does not involve movement
      of the capillary and both of its ends remain constantly in the solution during
      both sample injection and separation. The amount of sample introduced to the
      capillary is controlled by the duration of the pressure pulse. The new sample
      introduction method was tested in the determination of ammonia, creatinine, uric
      acid, and hippuric acid in human urine. The determination was performed in a
      capillary with an overall length of 10.5 cm, in two BGEs with compositions 50 mM
      MES + 5 mM NaOH (pH 5.1) and 1 M acetic acid + 1.5 mM crown ether 18-crown-6 (pH
      2.4). A dual contactless conductivity/UV spectrometric detector was used for the
      detection. 

PMID- 25752682
TI  - Establishing criteria for human mesenchymal stem cell potency.
AB  - This study sought to identify critical determinants of mesenchymal stem cell
      (MSC) potency using in vitro and in vivo attributes of cells isolated from the
      bone marrow of age- and sex-matched donors. Adherence to plastic was not
      indicative of potency, yet capacity for long-term expansion in vitro varied
      considerably between donors, allowing the grouping of MSCs from the donors into
      either those with high-growth capacity or low-growth capacity. Using this
      grouping strategy, high-growth capacity MSCs were smaller in size, had greater
      colony-forming efficiency, and had longer telomeres. Cell-surface biomarker
      analysis revealed that the International Society for Cellular Therapy (ISCT)
      criteria did not distinguish between high-growth capacity and low-growth capacity
      MSCs, whereas STRO-1 and platelet-derived growth factor receptor alpha were
      preferentially expressed on high-growth capacity MSCs. These cells also had the
      highest mean expression of the mRNA transcripts TWIST-1 and DERMO-1. Irrespective
      of these differences, both groups of donor MSCs produced similar levels of key
      growth factors and cytokines involved in tissue regeneration and were capable of
      multilineage differentiation. However, high-growth capacity MSCs produced
      approximately double the volume of mineralized tissue compared to low-growth
      capacity MSCs when assessed for ectopic bone-forming ability. The additional
      phenotypic criteria presented in this study when combined with the existing ISCT
      minimum criteria and working proposal will permit an improved assessment of MSC
      potency and provide a basis for establishing the quality of MSCs prior to their
      therapeutic application.

PMID- 25752684
TI  - Chloroquine and Hydroxychloroquine Increase Retinal Pigment Epithelial Layer
      Permeability.
AB  - Antimalarials chloroquine (CQ) and hydroxychloroquine (HCQ) are widely used as
      antiinflammatory drugs, but side effects include retinopathy and vision loss. The
      objective of this study was to examine the effect of CQ and HCQ on the barrier
      integrity of retinal pigment epithelial (RPE) cell monolayers in vitro.
      Permeability of ARPE-19 cell monolayers was determined using Fluorescein
      isothiocyanate (FITC)-labeled dextran. The influence of CQ and HCQ on cell death
      and the expression tight junction molecules was examined. CQ and HCQ
      significantly increased ARPE-19 monolayer permeability after 3 and 18 h,
      respectively, and enhanced mRNA levels for claudin-1 and occludin. Cytotoxicity
      was only observed after 18 h exposure. Thus, CQ and HCQ rapidly enhance RPE
      barrier permeability in vitro, independent of cytotoxicity or loss of zonula
      occludens-1, claudin-1, and occludin expression. Our findings suggest that CQ/HCQ
      induced permeability of the RPE layer may contribute to blood-retinal barrier
      breakdown in case of CQ/HCQ-induced retinopathy. 

PMID- 25752685
TI  - Clonal differences and impact of defoliation on Sauvignon blanc (Vitis vinifera
      L.) wines: a chemical and sensory investigation.
AB  - BACKGROUND: The aim of this study, performed on Sauvignon blanc clones SB11 and
      SB316, grafted on the same rootstock 101-14 Mgt (Vitis riparia * V. ruperstris)
      and grown at two adjacent vineyards, was two-fold: (1) to study wine chemical and
      sensory composition of both clones within an unaltered canopy; and (2) to
      determine the effect of defoliation (e.g. bunch microclimate) on wine chemical
      and sensory composition. RESULTS: Orthogonal projection to latent structures
      discriminate analysis (OPLS-DA) was applied to the concentration profiles of
      volatile compounds derived from gas chromatography-mass spectrometry data. The
      loadings directions inferred that 3-isobutyl-2-methoxypyrazine (IBMP)
      discriminated control treatments (shaded fruit zone) of both clones from
      defoliation treatments (exposed fruit zone), whereas 3-sulfanyl-hexan-1-ol (3SH),
      3-sulfanylhexyl acetate (3SHA), hexanol, hexyl hexanoate and some other esters
      discriminated defoliated treatments from the controls. The OPLS-DA indicated the
      importance of IBMP, higher alcohol acetates and phenylethyl esters, for
      discrimination of clone SB11 from clone SB316 irrespective of the treatment.
      Defoliation in the fruit zone significantly decreased perceived greenness in
      clone SB11 and elevated fruitier aromas, whereas in clone SB316 the effect of
      defoliation on wine sensory perception was less noticeable regardless the
      decrease in IBMP concentrations. CONCLUSION: These findings highlight the
      importance of clone selection and bunch microclimate to diversify produced wine
      styles.

PMID- 25752686
TI  - The role of 64-slice CT following perfusion with iohexol via the hepatopancreatic
      ampulla in assessing pancreaticobiliary junctions.
AB  - The aim of this study was to delineate the structure of the pancreatic and
      biliary ducts in premature infants using a novel imaging method. The duodenal
      papillae of 30 premature infant cadavers were dissected. The pancreatic and
      biliary ducts were visualized using 64-detector multislice spiral computed
      tomography (MSCT). Contrast agent was injected into the duodenal papilla via the
      hepatopancreatic ampulla of Vater. MSCT scanning revealed both the pancreatic and
      biliary ducts as well as the common channel in 18 cases. The bile duct was
      visualized in the remaining 12 cases. Four patterns of the pancreaticobiliary
      ductal junction were noted: Y-type (73.3%), U-type (13.3%), V-type (6.7%), and II
      type (6.7%). The results showed that MSCT and three-dimensional reconstruction
      can be used to visualize the junction pattern and common channel of the
      pancreatic and biliary ducts, and the structure of the surrounding tissue, in
      premature infants.

PMID- 25752687
TI  - Unexpected chemistry from the reaction of naphthyl and acetylene at combustion
      like temperatures.
AB  - The hydrogen abstraction/acetylene addition (HACA) mechanism has long been viewed
      as a key route to aromatic ring growth of polycyclic aromatic hydrocarbons (PAHs)
      in combustion systems. However, doubt has been drawn on the ubiquity of the
      mechanism by recent electronic structure calculations which predict that the HACA
      mechanism starting from the naphthyl radical preferentially forms acenaphthylene,
      thereby blocking cyclization to a third six-membered ring. Here, by probing the
      products formed in the reaction of 1- and 2-naphthyl radicals in excess acetylene
      under combustion-like conditions with the help of photoionization mass
      spectrometry, we provide experimental evidence that this reaction produces 1- and
      2-ethynylnaphthalenes (C12 H8 ), acenaphthylene (C12 H8 ) and
      diethynylnaphthalenes (C14 H8 ). Importantly, neither phenanthrene nor anthracene
      (C14 H10 ) was found, which indicates that the HACA mechanism does not lead to
      cyclization of the third aromatic ring as expected but rather undergoes ethynyl
      substitution reactions instead. 

PMID- 25752688
TI  - Predicting postoperative delirium after vascular surgical procedures.
AB  - OBJECTIVE: The objective of this study was to determine the incidence of and
      specific preoperative and intraoperative risk factors for postoperative delirium
      (POD) in electively treated vascular surgery patients. METHODS: Between March
      2010 and November 2013, all vascular surgery patients were included in a
      prospective database. Various preoperative, intraoperative, and postoperative
      risk factors were collected during hospitalization. The primary outcome variable
      was the incidence of POD. Secondary outcome variables were any surgical
      complication, hospital length of stay, and mortality. RESULTS: In total, 566
      patients were prospectively evaluated; 463 patients were 60 years or older at the
      time of surgery and formed our study cohort. The median age was 72 years
      (interquartile range, 66-77), and 76.9% were male. Twenty-two patients (4.8%)
      developed POD. Factors that differed significantly by univariate analysis
      included current smoking (P = .001), increased comorbidity (P = .001),
      hypertension (P = .003), diabetes mellitus (P = .001), cognitive impairment (P <
      .001), open aortic surgery or amputation surgery (P < .001), elevated C-reactive
      protein level (P < .001), and blood loss (P < .001). Multivariate logistic
      regression analysis revealed preoperative cognitive impairment (odds ratio [OR],
      16.4; 95% confidence interval [CI], 4.7-57.0), open aortic surgery or amputation
      surgery (OR, 14.0; 95% CI, 3.9-49.8), current smoking (OR, 10.5; 95% CI, 2.8
      40.2), hypertension (OR, 7.6; 95% CI, 1.9-30.5) and age >=80 years (OR, 7.3; 95%
      CI, 1.8-30.1) to be independent predictors of the occurrence of POD. The
      combination of these parameters allows us to predict delirium with a sensitivity
      of 86% and a specificity of 92%. The area under the curve of the corresponding
      receiver operating characteristics was 0.93. Delirium was associated with longer
      hospital length of stay (P < .001), more frequent and increased intensive care
      unit stays (P = .008 and P = .003, respectively), more surgical complications (P
      < .001), more postdischarge institutionalization (P < .001), and higher 1-year
      mortality rates (P = .0026). CONCLUSIONS: In vascular surgery patients,
      preoperative cognitive impairment and open aortic or amputation surgery were
      highly significant risk factors for the occurrence of POD. In addition, POD was
      significantly associated with a higher mortality and more institutionalization.
      Patients with these risk factors should be considered for high-standard delirium
      care to improve these outcomes.

PMID- 25752689
TI  - Discussion.

PMID- 25752690
TI  - Compartment syndrome of the foot associated with a delayed presentation of acute
      limb ischemia.
AB  - Compartment syndrome of the leg is a well-recognized complication known to follow
      urgent revascularization done for acute limb ischemia, but compartment syndrome
      of the foot has not been reported after the ischemia-reperfusion sequence. Herein
      we report a case of foot fasciotomy done for compartment syndrome that occurred
      after urgent revascularization. We suggest that foot fasciotomies should be
      considered in particular circumstances of acute lower leg ischemia, such as
      infrapopliteal thromboembolic events, prolonged ischemia, and persistent or
      worsening foot symptoms that follow revascularization and calf fasciotomies. 

PMID- 25752691
TI  - Low wall shear stress predominates at sites of abdominal aortic aneurysm rupture.
AB  - OBJECTIVE: Aortic diameter as the primary criterion in the decision to repair
      abdominal aortic aneurysms (AAAs) has drawbacks as some rupture below size
      thresholds, whereas others reach extreme size without rupture. Predictions of
      static aortic wall stress have also failed to reliably predict rupture potential.
      The objective of this study was to computationally assess blood flow
      characteristics at the site of infrarenal AAA rupture. On the basis of the finite
      element literature correlating rupture location with high static local wall
      stress, we hypothesized that a computational fluid dynamics approach would also
      demonstrate rupture at regions of high pressure and wall shear stress (WSS).
      METHODS: Three-dimensional AAA geometry was generated from computed tomography
      angiography images of seven ruptured AAAs. Aortic blood flow velocity, pressure,
      and WSS were computationally determined. Flow characteristics at the site of
      rupture were determined and compared across all cases. RESULTS: AAA size at the
      time of rupture was 8.3 +/- 0.9 cm. Only three of the seven AAAs ruptured at the
      site of maximal diameter. Blood flow velocity in the aneurysmal aorta showed
      dominant flow channels with zones of recirculation, where low WSS predominated.
      Regardless of aneurysm size or configuration, rupture occurred in or near these
      flow recirculation zones in all cases. WSS was significantly lower and thrombus
      deposition was more abundant at the site of rupture. CONCLUSIONS: This
      computational study was the first to assess blood flow characteristics at the
      site of infrarenal AAA rupture in realistic aortic geometries. In contradiction
      to our initial hypothesis, rupture occurred not at sites of high pressure and WSS
      but rather at regions of predicted flow recirculation, where low WSS and thrombus
      deposition predominated. These findings raise the possibility that this flow
      pattern may lead to thrombus deposition, which may elaborate adventitial
      degeneration and eventual AAA rupture.

PMID- 25752692
TI  - Contemporary outcomes of intact and ruptured visceral artery aneurysms.
AB  - OBJECTIVE: The treatment outcomes of ruptured visceral artery aneurysms (rVAAs)
      have been sparsely characterized, with no clear comparison between different
      treatment modalities. The purpose of this paper was to review the perioperative
      and long-term outcomes of open and endovascular interventions for intact visceral
      artery aneurysms (iVAAs) and rVAAs. METHODS: This was a retrospective review of
      all treated VAAs at one institution from 2003 to 2013. Patient demographics,
      aneurysm characteristics, management, and subsequent outcomes (technical success,
      mortality, reintervention) and complications were recorded. RESULTS: The study
      identified 261 patients; 181 patients were repaired (77 ruptured, 104 intact).
      Pseudoaneurysms were more common in rVAAs (81.8% vs 35.3% for iVAAs; P < .001).
      The rVAAs were smaller than the iVAAs (20.7 mm vs 27.5 mm; P = .018), and their
      most common presentation was abdominal pain; 29.7% were hemodynamically unstable.
      Endovascular intervention was the initial treatment modality for 67.4% (75.3% for
      rVAAs, 61.5% for iVAAs). The perioperative complication rate was higher for rVAAs
      (13.7% vs 1% for iVAAs; P = .003), as was mortality at 30 days (13% vs 0% for
      iVAAs; P = .001), 1 year (32.5% for rVAAs vs 4.1% for iVAAs; P < .001), and 3
      years (36.4% for rVAAs vs 8.3% for iVAAs; P < .001). Lower 30-day mortality was
      noted with endovascular repair for rVAAs (7.4% vs 28.6% open; P = .025).
      Predictors of mortality for rVAAs included age (odds ratio, 1.04; P = .002),
      whereas endovascular repair was protective (odds ratio, 0.43; P = .037). Mean
      follow-up was 26.2 months, and Kaplan-Meier estimates of survival were higher for
      iVAAs at 3 years (88% vs 62% for rVAAs; P = .045). The 30-day reintervention rate
      was higher for rVAAs (7.7% vs 19.5% for iVAAs; P = .019) but was similar between
      open and endovascular repair (8.2% vs 15%; P = NS). CONCLUSIONS: rVAAs have
      significant mortality. Open and endovascular interventions are equally durable
      for elective repair of VAAs, but endovascular interventions for rVAAs result in
      lower morbidity and mortality. Aggressive treatment of pseudoaneurysms is
      electively recommended at diagnosis regardless of size.

PMID- 25752693
TI  - Stenting of femoropopliteal lesions using interwoven nitinol stents.
AB  - OBJECTIVE: The Supera stent (Abbott Laboratories, Abbott Park, Ill) has a unique
      biomimetic design allowing axial and longitudinal flexibility and fracture
      resistance. The aim of this retrospective study was to assess the midterm patency
      of Supera stents used to treat patients with superficial femoral and popliteal
      arterial disease by a single practice. METHODS: From April 2010 to December 2011,
      53 patients and 59 limbs with symptomatic femoropopliteal lesions underwent
      angioplasty and stenting with the Supera stent. Five patients had no follow-up
      and were excluded. Demographics of the patients, radiographic images, morphologic
      features of the lesions, procedural reports, reinterventions, and follow-up
      clinical visit notes were reviewed. Primary patency was defined as clinical
      resolution of symptoms with no secondary interventions. Primary and secondary
      patency rates at 12, 24, and 36 months were estimated by Kaplan-Meier analysis.
      RESULTS: A total of 48 patients (42 men, six women; 54 limbs; mean age, 64.3
      years [range, 51-87]) received Supera stents and had at least one follow-up visit
      as part of their treatment for femoropopliteal disease. Primary indications for
      intervention included claudication, rest pain, and tissue loss, at rates of 54%
      (29 of 54), 26% (14 of 54), and 20% (11 of 54), respectively; 22% of lesions were
      TransAtlantic Inter-Society Consensus type A or B and 78% were type C or D. Mean
      lesion length was 24.0 cm (range, 3-51). Mean follow-up was 27.5 months (range, 1
      45). The ankle-brachial index increased from 0.58 +/- 0.20 preoperatively to 0.77
      +/- 0.18 postoperatively (P = .00004). Primary, primary assisted, and secondary
      patency rates at latest follow-up were 79.6%, 88.9%, and 92.3%, respectively.
      Cumulative primary patency rates by Kaplan-Meier analysis at 12, 24, and 36
      months were 85.6%, 83.1%, and 76.7%, respectively. Secondary patency rates by
      Kaplan-Meier estimates at 12, 24, and 36 months were 93.8%, 93.8%, and 89.3%,
      respectively. No stent fractures were found at the time of any reinterventions.
      Long lesions >30 cm (n = 18) showed equivalent patency to lesions of 1 to 15 cm
      (n = 18) and lesions 15 to 30 cm in length (n = 18). CONCLUSIONS: Our midterm
      results show that Supera stents are durable in treating femoropopliteal lesions,
      with notably high patency rates in patients with long lesion lengths.

PMID- 25752694
TI  - In patients stratified by preoperative risk, endovascular repair of ruptured
      abdominal aortic aneurysms has a lower in-hospital mortality and morbidity than
      open repair.
AB  - OBJECTIVE: Previous studies have reported that endovascular repair (EVAR) of
      ruptured abdominal aortic aneurysms (RAAAs) has lower postoperative mortality
      than open repair (OR). However, comparisons involved heterogeneous populations
      that lacked adjustment for preoperative risk. We hypothesize that for RAAA
      patients stratified by a validated measure of preoperative mortality risk, EVAR
      has a lower in-hospital mortality and morbidity than does OR. METHODS: In
      hospital mortality and morbidity after EVAR and OR of RAAA were compared in
      patients from the Vascular Quality Initiative (2003-2013) stratified by the
      validated Vascular Study Group of New England RAAA risk score into low-risk
      (score 0-1), medium-risk (score 2-3), and high-risk (score 4-6) groups. RESULTS:
      Among 514 patients who underwent EVAR and 651 patients who underwent OR of RAAA,
      EVAR had lower in-hospital mortality (25% vs 33%, P = .001). In risk-stratified
      patients, EVAR trended toward a lower mortality in the low-risk group (n = 626;
      EVAR, 10% vs OR, 15%; P = .07), had a significantly lower mortality in the medium
      risk group (n = 457; EVAR, 37% vs OR, 48%; P = .02), and no advantage in the high
      risk group (n = 82; EVAR, 95% vs OR, 79%; P = .17). Across all risk groups,
      cardiac complications (EVAR, 29% vs OR, 38%; P = .001), respiratory complications
      (EVAR, 28% vs OR, 46%; P < .0001), renal insufficiency (EVAR, 24% vs OR, 38%; P <
      .0001), lower extremity ischemia (EVAR, 2.7% vs OR, 8.1%; P < .0001), and bowel
      ischemia (EVAR, 3.9% vs OR, 10%; P < .0001) were significantly lower after EVAR
      than after OR. Across all risk groups, median (interquartile range) intensive
      care unit length of stay (EVAR, 2 [1-5] days vs OR, 6 [3-13] days; P < .0001) and
      hospital length of stay (EVAR, 6 [4-12] days vs OR, 13 [8-22] days; P < .0001)
      were lower after EVAR. CONCLUSIONS: This novel risk-stratified comparison using a
      national clinical database showed that EVAR of RAAA has a lower mortality and
      morbidity compared with OR in low-risk and medium-risk patients and that EVAR
      should be used to treat these patients when anatomically feasible. For RAAA
      patients at the highest preoperative risk, there is no benefit to using EVAR
      compared with OR.

PMID- 25752695
TI  - Discussion.

PMID- 25752696
TI  - A new selective chromogenic and turn-on fluorogenic probe for copper(II) in
      solution and vero cells: recognition of sulphide by [CuL].
AB  - A new coumarin-appended thioimidazole-linked imine conjugate, viz. has been
      synthesized and characterized. has been found to recognize Cu(2+) selectively
      among a wide range of biologically relevant metal ions. The chemosensing behavior
      of has been demonstrated through fluorescence, absorption, visual fluorescence
      color changes, ESI-MS and (1)H NMR titrations. The chemosensor showed selectivity
      toward Cu(2+) by switch on fluorescence among the 18 metal ions studied with a
      detection limit of 1.53 MUM. The complex formed between and Cu(2+) is found to be
      1 : 1 on the basis of absorption and fluorescence titrations and was confirmed by
      ESI-MS. DFT and TDDFT calculations were performed in order to demonstrate the
      structure of and [CuL] and the electronic properties of chemosensor and its
      copper complex. This highly fluorescent [CuL] complex has been used to recognize
      sulphide selectively among the other allied anions. Microstructural features of
      and its Cu(2+) complex have been investigated by SEM imaging (scanning electron
      microscopy). The biological applications of were evaluated in Vero cells and it
      was found to exhibit low cytotoxicity and good membrane permeability for the
      detection of Cu(2+). 

PMID- 25752697
TI  - Morphology and neurochemistry of rabbit iris innervation.
AB  - The aim of this study was to map the entire nerve architecture and sensory
      neuropeptide content of the rabbit iris. Irises from New Zealand rabbits were
      stained with antibodies against neuronal-class betaIII-tubulin, calcitonin gene
      related peptide (CGRP) and substance P (SP), and whole-mount images were acquired
      to build a two-dimensional view of the iridal nerve architecture. After taking
      images in time-lapse mode, we observed thick nerves running in the iris stroma
      close to the anterior epithelia, forming four to five stromal nerve rings from
      the iris periphery to the pupillary margin and sub-branches that connected with
      each other, constituting the stromal nerve plexus. In the anterior side, fine
      divisions derivated from the stromal nerves, forming a nerve network-like
      structure to innervate the superficial anterior border layer, with the pupillary
      margin having the densest innervation. In the posterior side, the nerve bundles
      ran along with the pupil dilator muscle in a radial pattern. The morphology of
      the iris nerves on both sides changed with pupil size. To obtain the relative
      content of the neuropeptides in the iris, the specimens were double stained with
      betaIII-tubulin and CGRP or SP antibodies. Relative nerve fiber densities for
      each fiber population were assessed quantitatively by computer-assisted analysis.
      On the anterior side, CGRP-positive nerve fibers constituted about 61%, while SP
      positive nerves constitute about 30.5%, of the total nerve content, which was
      expressed as betaIII tubulin-positive fibers. In addition, in the anterior stroma
      of the collarette region, there were non-neuronal cells that were positive for
      SP. On the posterior side, CGRP-positive nerve fibers were about 69% of total
      nerve content, while SP constituted only up to 20%. Similarly, in the trigeminal
      ganglia (TG), the number of CGRP-positive neurons significantly outnumbered those
      that were positive for SP. Also, all the SP-positive neurons were labeled with
      CGRP. This is the first study to provide a two-dimensional whole mount and a
      cross-sectional view of the entire iris nerve architecture. Considering the
      anatomical location, the high expression of CGRP and SP suggests that these
      neuropeptides may play a role in the pathogenesis of anterior uveitis, glaucoma,
      cataracts and chronic ocular pain. 

PMID- 25752698
TI  - MMP-9 inhibition facilitates amacrine cell loss after ouabain-induced retinal
      damage.
AB  - Retinal ischemia is a common risk factor for visual impairment and blindness. Two
      common changes after retinal ischemia are retinal ganglion cell (RGC) loss and
      Muller glial cell (MGC)-mediated endogenous repair. Matrix metalloproteinase 9
      (MMP-9) has been shown to be responsible to RGC death. However, the effects of
      MMP-9 on the loss of other neurons and the reactivity of MGCs after retinal
      injury remain unclear. Ouabain, a Na/K-ATPase inhibitor, was injected into the
      vitreous body of rat eyes to induce cell death in the inner nuclear layer (INL).
      MMP-9 expression and activation in the retinas were examined by gelatin
      zymography and immunohistochemistry. The role of MMP-9 inhibitor (MMP-9i) in
      ouabain-treated retinas was assessed. After ouabain injection, there was an
      upregulation of MMP-9 activity in the inner retinas, and the activation of MMP-9
      reached a maximum at 2 day. Unexpectedly, MMP-9i enhanced the thinning of the
      INL, the loss of Calbindin D-28k-positive cells and Syntaxin-positive amacrine
      cells (ACs) in the INL and decreased levels of Calbindin D-28k protein, while
      leaving the outer nuclear layer (ONL) unchanged. In addition, MMP-9i led to a
      minor increase in the number of BrdU positive cells that did not express GS in
      the INL. Collectively, these results revealed that the inhibition of MMP-9
      activity facilitated AC loss and promoted the generation of MGC-derived cells in
      ouabain-treated retinas, which indicates that treating retinal diseases with
      drugs that inhibit MMP-9 activity should be considered with caution.

PMID- 25752699
TI  - p53 suppresses tetraploid development in mice.
AB  - Mammalian tetraploid embryos die in early development because of defects in the
      epiblast. Experiments with diploid/tetraploid chimeric mice, obtained via the
      aggregation of embryonic stem cells, clarified that while tetraploid cells are
      excluded from epiblast derivatives, diploid embryos with tetraploid
      extraembryonic tissues can develop to term. Today, this method, known as
      tetraploid complementation, is usually used for rescuing extraembryonic defects
      or for obtaining completely embryonic stem (ES) cell-derived pups. However, it is
      still unknown why defects occur in the epiblast during mammalian development.
      Here, we demonstrated that downregulation of p53, a tumour suppressor protein,
      rescued tetraploid development in the mammalian epiblast. Tetraploidy in
      differentiating epiblast cells triggered p53-dependent cell-cycle arrest and
      apoptosis, suggesting the activation of a tetraploidy checkpoint during early
      development. Finally, we found that p53 downregulation rescued tetraploid embryos
      later in gestation. 

PMID- 25752700
TI  - Bioinspired tuning of hydrogel permeability-rigidity dependency for 3D cell
      culture.
AB  - Hydrogels are being extensively used for three-dimensional immobilization and
      culture of cells in fundamental biological studies, biochemical processes, and
      clinical treatments. However, it is still a challenge to support viability and
      regulate phenotypic activities of cells in a structurally stable gel, because the
      gel becomes less permeable with increasing rigidity. To resolve this challenge,
      this study demonstrates a unique method to enhance the permeability of a cell
      laden hydrogel while avoiding a significant change in rigidity of the gel.
      Inspired by the grooved skin textures of marine organisms, a hydrogel is
      assembled to present computationally optimized micro-sized grooves on the
      surface. Separately, a gel is engineered to preset aligned microchannels similar
      to a plant's vascular bundles through a uniaxial freeze-drying process. The
      resulting gel displays significantly increased water diffusivity with reduced
      changes of gel stiffness, exclusively when the microgrooves and microchannels are
      aligned together. No significant enhancement of rehydration is achieved when the
      microgrooves and microchannels are not aligned. Such material design greatly
      enhances viability and neural differentiation of stem cells and 3D neural network
      formation within the gel. 

PMID- 25752702
TI  - Tandem gold/silver-catalyzed cycloaddition/hydroarylation of 7-aryl-1,6-enynes to
      form 6,6-diarylbicyclo[3.2.0]heptanes.
AB  - Mixtures of [{PCy2(o-biphenyl)}AuCl] and AgSbF6 catalyze the tandem
      cycloaddition/hydroarylation of 7-aryl-1,6-enynes with electron-rich arenes to
      form 6,6-diarylbicyclo[3.2.0]heptanes in good yield under mild conditions.
      Experimental observations point to a mechanism involving gold-catalyzed
      cycloaddition followed by silver-catalyzed hydroarylation of a bicyclo[3.2.0]hept
      1(7)-ene intermediate.

PMID- 25752701
TI  - p14(ARF) Prevents Proliferation of Aneuploid Cells by Inducing p53-Dependent
      Apoptosis.
AB  - Weakening the Spindle Assembly Checkpoint by reduced expression of its components
      induces chromosome instability and aneuploidy that are hallmarks of cancer cells.
      The tumor suppressor p14(ARF) is overexpressed in response to oncogenic stimuli
      to stabilize p53 halting cell progression. Previously, we found that lack or
      reduced expression of p14(ARF) is involved in the maintenance of aneuploid cells
      in primary human cells, suggesting that it could be part of a pathway controlling
      their proliferation. To investigate this aspect further, p14(ARF) was ectopically
      expressed in HCT116 cells after depletion of the Spindle Assembly Checkpoint MAD2
      protein that was used as a trigger for aneuploidy. p14(ARF) Re-expression reduced
      the number of aneuploid cells in MAD2 post-transcriptionally silenced cells. Also
      aberrant mitoses, frequently displayed in MAD2-depleted cells, were decreased
      when p14(ARF) was expressed at the same time. In addition, p14(ARF) ectopic
      expression in MAD2-depleted cells induced apoptosis associated with increased p53
      protein levels. Conversely, p14(ARF) ectopic expression did not induce apoptosis
      in HCT116 p53KO cells. Collectively, our results suggest that the tumor
      suppressor p14(ARF) may have an important role in counteracting proliferation of
      aneuploid cells by activating p53-dependent apoptosis.

PMID- 25752703
TI  - Determination of radionuclides in samples of middle-aged and older human femurs.
AB  - The paper presents the studies of the presence of gamma isotopes and (90)Sr in 19
      middle-to old-aged human femur samples. The samples were taken up during routine
      orthopedic operations in 2012. The aim of the paper was determination of some
      radionuclides in human bones and estimation of radiation dose created by (90)Sr
      and (90)Y (in bones). The (137)Cs, (40)K, (226)Ra, (228)Th, (234)Th and (210)Pb
      isotopes were determined by gamma spectrometry. The above mentioned radionuclide
      contents were in the ranges: (137)Cs (0.04-1.45); (40)K (13-86); (226)Ra (1
      21.5); (228)Th (1.4-40.2); (234)Th (0.4-5.7); (210)Pb (0.7-8.4) Bq/kg d.w. (90)Sr
      was assayed based on radiometric measurement of ingrown (90)Y. The (90)Sr content
      was in the range 0.27-1.85 Bq/kg d.w. Measurements of concentration of (90)Sr and
      (90)Y in bones were used to estimation of health risk by calculation of radiation
      dose. Adsorbed doses ranged from 2.7 . 10(-7) to 1.9 . 10(-6) Gy/y for (90)Sr and
      from 1.2 . 10(-6) to 8.3 . 10(-7) Gy/y for (90)Y.

PMID- 25752704
TI  - Surface charge accumulation of particles containing radionuclides in open air.
AB  - Radioactivity can induce charge accumulation on radioactive particles. However,
      electrostatic interactions caused by radioactivity are typically neglected in
      transport modeling of radioactive plumes because it is assumed that ionizing
      radiation leads to charge neutralization. The assumption that electrostatic
      interactions caused by radioactivity are negligible is evaluated here by
      examining charge accumulation and neutralization on particles containing
      radionuclides in open air. A charge-balance model is employed to predict charge
      accumulation on radioactive particles. It is shown that particles containing
      short-lived radionuclides can be charged with multiple elementary charges through
      radioactive decay. The presence of radioactive particles can significantly modify
      the particle charge distribution in open air and yield an asymmetric bimodal
      charge distribution, suggesting that strong electrostatic particle interactions
      may occur during short- and long-range transport of radioactive particles.
      Possible effects of transported radioactive particles on electrical properties of
      the local atmosphere are reported. The study offers insight into transport
      characteristics of airborne radionuclides. Results are useful in atmospheric
      transport modeling of radioactive plumes. 

PMID- 25752705
TI  - Log-normality of indoor radon data in the Walloon region of Belgium.
AB  - The deviations of the distribution of Belgian indoor radon data from the log
      normal trend are examined. Simulated data are generated to provide a theoretical
      frame for understanding these deviations. It is shown that the 3-component
      structure of indoor radon (radon from subsoil, outdoor air and building
      materials) generates deviations in the low- and high-concentration tails, but
      this low-C trend can be almost completely compensated by the effect of
      measurement uncertainties and by possible small errors in background subtraction.
      The predicted low-C and high-C deviations are well observed in the Belgian data,
      when considering the global distribution of all data. The agreement with the log
      normal model is improved when considering data organised in homogeneous
      geological groups. As the deviation from log-normality is often due to the low-C
      tail for which there is no interest, it is proposed to use the log-normal fit
      limited to the high-C half of the distribution. With this prescription, the vast
      majority of the geological groups of data are compatible with the log-normal
      model, the remaining deviations being mostly due to a few outliers, and rarely to
      a "fat tail". With very few exceptions, the log-normal modelling of the high
      concentration part of indoor radon data is expected to give reasonable results,
      provided that the data are organised in homogeneous geological groups. 

PMID- 25752706
TI  - Sorption of radioiodide in an acidic, nutrient-poor boreal bog: insights into the
      microbial impact.
AB  - Batch sorption experiments were conducted to evaluate the sorption behaviour of
      iodide and the microbial impact on iodide sorption in the surface moss,
      subsurface peat, gyttja, and clay layers of a nutrient-poor boreal bog. The batch
      distribution coefficient (Kd) values of iodide decreased as a function of
      sampling depth. The highest Kd values, 4800 L/Kg dry weight (DW) (geometric
      mean), were observed in the fresh surface moss and the lowest in the bottom clay
      (geometric mean 90 mL/g DW). In the surface moss, peat and gyttja layers, which
      have a high organic matter content (on average 97%), maximum sorption was
      observed at a pH between ~ 4 and 5 and in the clay layer at pH 2. The Kd values
      were significantly lower in sterilized samples, being 20-fold lower than the
      values found for the unsterilized samples. In addition, the recolonization of
      sterilized samples with a microbial population from the fresh samples restored
      the sorption capacity of surface moss, peat and gyttja samples, indicating that
      the decrease in the sorption was due to the destruction of microbes and
      supporting the hypothesis that microbes are necessary for the incorporation of
      iodide into the organic matter. Anoxic conditions reduced the sorption of iodide
      in fresh, untreated samples, similarly to the effect of sterilization, which
      supports the hypothesis that iodide is oxidized into I2/HIO before incorporation
      into the organic matter. Furthermore, the Kd values positively correlated with
      peroxidase activity in surface moss, subsurface peat and gyttja layers at +20 
      degrees C, and with the bacterial cell counts obtained from plate count agar at
      +4  degrees C. Our results demonstrate the importance of viable microbes for the
      sorption of iodide in the bog environment, having a high organic matter content
      and a low pH.

PMID- 25752707
TI  - Estimation of effective dose during hystrosalpingography procedures in certain
      hospitals in Sudan.
AB  - The aims of this study were to measure the patients' entrance surface air kerma
      doses (ESAK), effective doses and to compare practices between different
      hospitals in Sudan. ESAK were measured for patient using calibrated thermo
      luminance dosimeters (TLDs, GR200A). Effective doses were estimated using
      National radiological Protection Board (NRPB) software. This study was conducted
      in five radiological departments: Two Teaching Hospitals (A and D), two private
      hospitals (B and C) and one University Hospital (E). The mean ESAK was 20.1mGy,
      28.9mGy, 13.6mGy, 17.5mGy, 35.7mGy for hospitals A, B, C, D, and E, respectively.
      The mean effective dose was 2.4mSv, 3.5mSv, 1.6mSv, 2.1mSv and 4.3mSv in the same
      order. The study showed wide variations in the ESDs with three of the hospitals
      having values above the internationally reported values. 

PMID- 25752712
TI  - Biliary tract: Therapeutic strategies for cholangiocarcinoma-wishing on WNT
      inhibitors?

PMID- 25752711
TI  - Nanomedicines in gastroenterology and hepatology.
AB  - Nanoscale systems are currently under investigation for multiple different
      diagnostic and therapeutic applications. These systems can be used to identify
      pathologically changed tissues or to selectively deliver drugs to these sites;
      both applications have an extremely high potential to ameliorate therapeutic
      outcomes for patients. Tissues as well as single cells can be targeted because of
      the small size of these systems, which enables enhanced diagnosis and increased
      specificity of therapy. Drug loads can be delivered directly to the site of
      action, which can result in a reduction in incidence and severity of adverse
      systemic effects. Several nano-based platform technologies are currently under
      investigation for use in therapeutic approaches, mainly for anti-inflammatory and
      anti-cancer therapies. Although many nanoscale systems show promising therapeutic
      outcomes in preclinical studies, only a limited number are ready for clinical
      use. This Review will discuss the diverse nanomaterials currently available and
      the first specific uses for select gastroenterological and hepatological
      pathologies. The discussion of diagnostic and therapeutic applications will
      consider realities of market introduction of these sometimes very complex systems
      in light of remaining regulatory challenges and hurdles for industrial
      production.

PMID- 25752714
TI  - Infectious complications in bullous pemphigoid: an analysis of risk factors.
AB  - BACKGROUND: Infections are common in bullous pemphigoid and contribute to
      significant mortality. OBJECTIVES: We sought to define the spectrum of infectious
      complications and to identify associated risk factors in a bullous pemphigoid
      cohort. DESIGN: A retrospective cohort study conducted at an academic medical
      center. RESULTS: In all, 97 patients were included. Infectious complications
      occurred in 54 patients (56%) and the median duration from diagnosis to first
      episode of infection was 3 months. Bacteremia occurred in 14 patients (26%) and
      26 of 30 deaths (87%) were attributable to infections. On univariate analysis,
      significant risk factors include low Karnofsky score (<60) (odds ratio [OR] 3.5,
      95% confidence interval [CI] 1.5-8.3; P < .01), high Charlson comorbidity index
      score (>=6) (OR 2.4, 95% CI 1.1-5.5; P = .04), and dementia (OR 4.9, 95% CI 1.5
      15.8; P = .01). On multivariate analysis, low Karnofsky score and dementia
      remained significant with an OR of 3.3 (95% CI 1.1-10.0; P = .03) and OR of 4.2
      (95% CI 1.2-14.7; P = .03), respectively. LIMITATIONS: Limitations include
      potential selection bias as a result of study design and primary outcome measures
      focused on significant infections requiring hospitalizations. Minor infections
      were not included. CONCLUSIONS: Identified risk factors for infectious
      complications include functional impairment and the presence of dementia, which
      may allow for better risk stratification and individualized treatment of bullous
      pemphigoid.

PMID- 25752715
TI  - Duration of oral antibiotic therapy for the treatment of adult acne: a
      retrospective analysis investigating adherence to guideline recommendations and
      opportunities for cost-savings.
AB  - BACKGROUND: The duration of oral antibiotic acne therapy for adolescents compared
      with guidelines was recently investigated; however it was uncertain if duration
      of antibiotics for adult acne therapy differed. OBJECTIVE: This study aimed to
      evaluate duration of oral antibiotics for adult acne compared with guidelines and
      determine possible cost-savings. METHODS: This was a retrospective cohort study
      of MarketScan Commercial Claims and Encounters database that incorporated claims
      data to determine duration and costs of antibiotic treatment among adults ages 21
      years and older. RESULTS: Of 17,448 courses, 84.5% (14,737) aligned with duration
      guidelines, although 12,040 (69.0%) courses did not include concomitant topical
      retinoid therapy. Mean savings of $592.26 per person could result if prolonged
      courses met guidelines. Mean (median) costs of generic and branded formulations
      for the most frequent course duration (90-179 days) were $103.77 ($54.27) and
      $1421.61 ($1462.25), respectively. LIMITATIONS: Actual patient prescription
      adherence is uncertain and database lacks information regarding acne severity,
      patient physical characteristics, and clinical outcomes. CONCLUSIONS: The
      majority of oral antibiotic course durations follow guidelines, although topical
      retinoids are underused. Costs of antibiotic therapy were lower for shorter
      courses and those using generic medications; the cost-effectiveness of these
      modifications has not been investigated.

PMID- 25752716
TI  - Neurotrophin receptors and perineural invasion in desmoplastic melanoma.
AB  - BACKGROUND: Perineural invasion (PNI) in desmoplastic melanoma is associated with
      increased local recurrence and reduced disease-free survival. The biological
      mechanisms underlying PNI remain unclear although several lines of evidence
      implicate neurotrophins and their receptors. OBJECTIVES: We investigated the
      expression of p75NGFR and TrkA, and the presence of functional RET polymorphism
      (RETp) as they relate to PNI in desmoplastic melanoma. METHODS: In all, 43 cases
      of desmoplastic melanoma were immunohistochemically evaluated for TrkA and
      p75NGFR expression and RETp was detected by direct DNA sequencing. RESULTS: PNI
      was present in 67% of cases. On univariate analysis, p75NGFR was associated with
      PNI (expression detected in 79% of PNI-positive cases compared with 36% of PNI
      negative cases, P = .005), increased Breslow depth (P = .007), and greater Clark
      level (P = .01). RETp was noted in 28% of cases but was not significantly
      associated with PNI (P = .27) or other histopathologic variables. TrkA expression
      was absent in all cases. PNI was associated with increased Breslow depth and
      Clark level (P = .01 and P = .009, respectively). Controlling for the association
      between p75NGFR and depth, p75NGFR remained associated with an increased
      propensity for PNI (odds ratio 4.68, P = .04). LIMITATIONS: The sample size was
      limited. CONCLUSION: In desmoplastic melanoma, p75NGFR expression is
      significantly associated with PNI and a more locally aggressive phenotype.

PMID- 25752717
TI  - Lateral calcaneal artery perforator-based skin flaps for coverage of lower
      posterior heel defects.
AB  - BACKGROUND: Perforator-based flaps have been explored across almost all of the
      lower leg except in the Achilles tendon area. This paper introduced a perforator
      flap sourced from this area with regard to its anatomic basis and clinical
      applications. METHODS: Twenty-four adult cadaver legs were dissected to
      investigate the perforators emerging along the lateral edge of the Achilles
      tendon in terms of number and location relative to the tip of the lateral
      malleolus, and distribution. Based on the anatomic findings, perforator flaps,
      based on the perforator(s) of the lateral calcaneal artery (LCA) alone or in
      concert with the perforator of the peroneal artery (PA), were used for
      reconstruction of lower-posterior heel defects in eight cases. Postoperatively,
      subjective assessment and Semmes-Weinstein filament test were performed to
      evaluate the sensibility of the sural nerve-innerved area. RESULTS: The PA ended
      into the anterior perforating branch and LCA at the level of 6.0 +/- 1.4 cm
      (range 3.3-9.4 cm) above the tip of the lateral malleolus. Both PA and LCA,
      especially the LCA, gave rise to perforators to contribute to the integument
      overlying the Achilles tendon. Of eight flaps, six were based on perforator(s) of
      the LCA and two were on perforators of the PA and LCA. Follow-up lasted for 6-28
      months (mean 13.8 months), during which total flap loss and nerve injury were not
      found. Functional and esthetic outcomes were good in all patients. CONCLUSION:
      The integument overlying the Achilles tendon gets its blood supply through the
      perforators of the LCA primarily and that of through the PA secondarily. The LCA
      perforator(s)-based and the LCA plus PA perforators-based stepladder flap is a
      reliable, sensate flap, and should be thought of as a valuable procedure of
      choice for coverage of lower-posterior heel defects in selected patients.

PMID- 25752718
TI  - The drain game: Abdominal drains for transverse rectus abdominis myocutaneous
      breast reconstruction.
AB  - INTRODUCTION: We recently published data for the duration of donor site drain use
      in latissimus dorsi and deep inferior epigastric perforator breast
      reconstruction, due to a reported requirement in the literature; evidence is
      still required for transverse rectus abdominis myocutaneous (TRAM)
      reconstruction. AIM: To compare inpatient hospital stay, drainage parameters and
      donor-site complications associated with closed suction abdominal drain removal
      by post-operative day (POD) 3 regardless of output (early group), versus after
      POD 3 where instructions were by drainage volume/24 h +/- output consistency
      (late group), in post-mastectomy TRAM breast reconstruction. METHOD: A
      retrospective review of TRAM breast reconstructions, between June 2008-2013, was
      undertaken with a minimum 1 year follow-up per patient. RESULTS: Of 65 patients
      who underwent TRAM breast reconstruction, 56 hospital records contained complete
      documentation. Both the late (n = 35) and early (n = 21) drain removal group were
      matched for age and number of donor site drains (2 per patient). Mean drain
      removal day (5.34 +/- 0.20 days vs. 2.67 +/- 0.14 days; p < 0.0001), total
      drainage (797.86 +/- 77.15 mls vs. 295.71 +/- 29.72 mls; p < 0.0001) and hospital
      inpatient stay (7.46 +/- 0.29 days vs. 6.09 +/- 0.32 days; p = 0.003) were
      greater for patients in the late versus early group. There were no differences in
      total complications (5.71% (2/35) vs. 14.29% (3/21); p = 0.28), including seroma
      (2.86% (1/35) vs. 4.76% (1/21); p = 0.71) rates between the late and early
      groups. DISCUSSION: These data suggest significant advantages for patients who
      have abdominal drains removed early by POD 3, without increased post-operative
      complications including seroma rates; these data are in keeping with our LD data.
      We recommend drain removal by POD 3.

PMID- 25752719
TI  - Self-assembling knots of controlled topology by designing the geometry of patchy
      templates.
AB  - The self-assembly of objects with a set of desired properties is a major goal of
      material science and physics. A particularly challenging problem is that of self
      assembling structures with a target topology. Here we show by computer simulation
      that one may design the geometry of string-like rigid patchy templates to promote
      their efficient and reproducible self-assembly into a selected repertoire of non
      planar closed folds including several knots. In particular, by controlling the
      template geometry, we can direct the assembly process so as to strongly favour
      the formation of constructs tied in trefoil or pentafoil, or even of more exotic
      torus knots. Polydisperse and racemic mixtures of helical fragments of variable
      composition add further tunability in the topological self-assembly we
      discovered. Our results should be relevant to the design of new ways to
      synthesize molecular knots, which may prove, for instance, to be efficient cargo
      carriers due to their mechanical stability. 

PMID- 25752720
TI  - Target and organ dose estimation from intensity modulated head and neck radiation
      therapy using 3 deformable image registration algorithms.
AB  - PURPOSE: To estimate the delivered dose to targets and organs at risk for head
      and neck radiation therapy by accumulating the dose using 3 deformable image
      registration (DIR) algorithms. METHODS AND MATERIALS: Five head and neck
      patients, who had daily cone beam computed tomography (CT) images taken during
      the course of treatment, were retrospectively studied. To overcome the small
      field of view limitations and Hounsfield unit uncertainties of cone beam CT, a
      planning CT was deformably registered and resampled onto each cone beam CT image
      with a 4.2-cm uniform field of view expansion. The "dose of the day" was
      calculated on these resampled CT images, warped, and accumulated to the planning
      CT using 3 different DIR algorithms. Dosimetric indices for targets and organs at
      risk were determined from dose-volume histograms and compared with corresponding
      planned quantities. RESULTS: There were no significant differences among the
      cumulative dose-volume histograms estimated by the 3 DIR algorithms. The
      cumulative mean dose deviation was less than 2% from the corresponding plan dose
      in general for the planning and gross tumor volumes. However, the parotid gland
      mean dose showed a large variation, with a maximum 33% deviation. This was due in
      part to considerable patient weight loss during the first 3 weeks of treatment.
      The corresponding target and organ mean dose deviations +/- standard deviation,
      estimated as an average of the 3 DIR algorithms, were 1.0 +/- 1.6% for planning
      target volumes, 1.6 +/- 2.3% for gross tumor volumes, 7.3 +/- 9.6% for left
      parotid, 10.3 +/- 11.9% for right parotid, and 3.3 +/- 4.7% for mucosa. The
      target coverage deviation (dose to 95% of the volume) was -2.8 +/- 1.8% for
      planning target volumes and 0.2 +/- 2.8% for gross tumor volumes. The deviation
      of the maximum dose to the spinal cord was 2.1 +/- 2.4%. CONCLUSIONS: Results of
      this study indicate that the estimated target dose generally remains within 2% of
      the intended dose for plans with a 5-mm planning margin. More frequent plan
      adaptation might be beneficial to avoid unintended excessive dose to parotid
      glands.

PMID- 25752721
TI  - Hindlimb unweighting does not alter vasoconstrictor responsiveness and nitric
      oxide-mediated inhibition of sympathetic vasoconstriction.
AB  - KEY POINTS: Physical inactivity increases the risk of cardiovascular disease and
      may alter sympathetic nervous system control of vascular resistance. Hindlimb
      unweighting (HU), a rodent model of physical inactivity, has been shown to
      diminish sympathetic vasoconstrictor responsiveness and reduce NO synthase
      expression in isolated skeletal muscle blood vessels. Our understanding of the
      effects of HU on sympathetic vascular regulation in vivo is very limited. The
      present findings demonstrate that HU did not alter sympathetic vasoconstrictor
      responsiveness and NO-mediated inhibition of sympathetic vasoconstriction in
      resting and contracting skeletal muscle. This study suggests that short-term
      physical inactivity does not alter in vivo sympathetic vascular control in the
      skeletal muscle vascular bed at rest and during contraction. ABSTRACT: We tested
      the hypothesis that physical inactivity would increase sympathetic
      vasoconstrictor responsiveness and diminish NO-mediated inhibition of sympathetic
      vasoconstriction in resting and contracting skeletal muscle. Sprague-Dawley rats
      (n = 33) were randomly assigned to sedentary time control (S) or hindlimb
      unweighted (HU) groups for 21 days. Following the intervention, rats were
      anaesthetized and instrumented for measurement of arterial blood pressure and
      femoral artery blood flow and stimulation of the lumbar sympathetic chain. The
      percentage change of femoral vascular conductance (%FVC) in response to
      sympathetic chain stimulation delivered at 2 and 5 Hz was determined at rest and
      during triceps surae muscle contraction before (control) and after NO synthase
      blockade with l-NAME (5 mg kg i.v.). Sympathetic vasoconstrictor responsiveness
      was not different (P > 0.05) in S and HU rats at rest (S, 2 Hz, -26 +/- 8% and 5
      Hz, -46 +/- 12%; and HU, 2 Hz, -29 +/- 9% and 5 Hz, -51 +/- 10%) and during
      contraction (S, 2 Hz, -10 +/- 7% and 5 Hz, -23 +/- 11%; and HU, 2 Hz, -9 +/- 5%
      and 5 Hz, -22 +/- 7%). Nitric oxide synthase blockade caused a similar increase
      (P > 0.05) in sympathetic vasoconstrictor responsiveness in HU and S rats at rest
      (S, 2 Hz, -41 +/- 7% and 5 Hz, -58 +/- 8%; and HU, 2 Hz, -43 +/- 6% and 5 Hz, -63
      +/- 8%) and during muscle contraction (S, 2 Hz, -15 +/- 6% and 5 Hz, -31 +/- 11%;
      and HU, 2 Hz, -12 +/- 5% and 5 Hz, -29 +/- 8%). Skeletal muscle NO synthase
      expression and ACh-mediated vasodilatation were also not different between HU and
      S rats. These data suggest that HU does not alter sympathetic vasoconstrictor
      responsiveness and NO-mediated inhibition of sympathetic vasoconstriction in
      resting and contracting skeletal muscle.

PMID- 25752722
TI  - Ischemic left ventricular aneurysm and anticoagulation: is it the clot or the
      plot that needs thinning?

PMID- 25752723
TI  - Anticoagulation in ischemic left ventricular aneurysm.
AB  - OBJECTIVE: To evaluate the role of systemic anticoagulation using warfarin in
      patients with post-myocardial infarction left ventricular (LV) aneurysm formation
      with or without definite LV thrombus formation. PATIENTS AND METHODS: This study
      included 648 patients with post-myocardial infarction LV aneurysm formation
      diagnosed retrospectively by 2-dimensional echocardiography from December 1,
      1994, to February 29, 2012. Of these 648 patients, 106 patients received warfarin
      and 542 patients did not. We studied a composite of death, nonfatal myocardial
      infarction, cerebrovascular accident, and systemic embolization as the primary
      outcome and a composite of cerebrovascular accident and systemic embolization as
      the secondary outcome by using propensity score-adjusted multiple Cox
      proportional hazards regression analysis. RESULTS: In patients with LV aneurysm,
      LV thrombus was observed in 89 patients (13.7%) and it was associated with a
      higher incidence of adverse secondary events (hazard ratio [HR], 3.63; 95% CI,
      1.12-11.8; P=.03) in unadjusted analysis. However, in adjusted analysis,
      anticoagulation did not predict either a better or a worse outcome for primary
      outcomes (HR, 1.05; 95% CI, 0.67-1.64; P=.84) or for secondary outcomes (HR,
      1.52; 95% CI, 0.670-3.46; P=.31). The benefit of anticoagulation was also not
      established in patients with LV thrombus (HR, 1.38; 95% CI, 0.32-5.97; P=.66).
      CONCLUSION: In patients with ischemic LV aneurysms, oral anticoagulation therapy
      with warfarin may not be effective enough to reduce cardiac and cerebrovascular
      events including systemic embolism. Further studies are needed to confirm this
      finding.

PMID- 25752724
TI  - Negative emotions towards others are diminished in remitted major depression.
AB  - BACKGROUND: One influential view is that vulnerability to major depressive
      disorder (MDD) is associated with a proneness to experience negative emotions in
      general. In contrast, blame attribution theories emphasise the importance of
      blaming oneself rather than others for negative events. Our previous exploratory
      study provided support for the attributional hypothesis that patients with
      remitted MDD show no overall bias towards negative emotions, but a selective bias
      towards emotions entailing self-blame relative to emotions that entail blaming
      others. More specifically, we found a decreased proneness for contempt/disgust
      towards others relative to oneself (i.e. self-contempt bias). Here, we report a
      definitive test of the competing general negative versus specific attributional
      bias theories of MDD. METHODS: We compared a medication-free remitted MDD (n=101)
      and a control group (n=70) with no family or personal history of MDD on a
      previously validated experimental test of moral emotions. The task measures
      proneness to specific emotions associated with different types of self-blame
      (guilt, shame, self-contempt/disgust, self-indignation/anger) and blame of others
      (other-indignation/anger, other-contempt/disgust) whilst controlling for the
      intensity of unpleasantness. RESULTS: We confirmed the hypothesis that patients
      with MDD exhibit an increased self-contempt bias with a reduction in
      contempt/disgust towards others. Furthermore, they also showed a decreased
      proneness for indignation/anger towards others. CONCLUSIONS: This corroborates
      the prediction that vulnerability to MDD is associated with an imbalance of
      specific self- and other-blaming emotions rather than a general increase in
      negative emotions. This has important implications for neurocognitive models and
      calls for novel focussed interventions to rebalance blame in MDD.

PMID- 25752725
TI  - Schizophrenia patients with high intelligence: A clinically distinct sub-type of
      schizophrenia?
AB  - BACKGROUND: Schizophrenia patients are typically found to have low IQ both pre-
      and post-onset, in comparison to the general population. However, a subgroup of
      patients displays above average IQ pre-onset. The nature of these patients'
      illness and its relationship to typical schizophrenia is not well understood. The
      current study sought to investigate the symptom profile of high-IQ schizophrenia
      patients. METHODS: We identified 29 schizophrenia patients of exceptionally high
      pre-morbid intelligence (mean estimated pre-morbid intelligence quotient (IQ) of
      120), of whom around half also showed minimal decline (less than 10 IQ points)
      from their estimated pre-morbid IQ. We compared their symptom scores (SAPS, SANS,
      OPCRIT, MADRS, GAF, SAI-E) with a comparison group of schizophrenia patients of
      typical IQ using multinomial logistic regression. RESULTS: The patients with very
      high pre-morbid IQ had significantly lower scores on negative and disorganised
      symptoms than typical patients (RRR=0.019; 95% CI=0.001, 0.675, P=0.030), and
      showed better global functioning and insight (RRR=1.082; 95% CI=1.020, 1.148;
      P=0.009). Those with a minimal post-onset IQ decline also showed higher levels of
      manic symptoms (RRR=8.213; 95% CI=1.042, 64.750, P=0.046). CONCLUSIONS: These
      findings provide evidence for the existence of a high-IQ variant of schizophrenia
      that is associated with markedly fewer negative symptoms than typical
      schizophrenia, and lends support to the idea of a psychosis spectrum or continuum
      over boundaried diagnostic categories.

PMID- 25752726
TI  - Age, sex and personality in early cannabis use.
AB  - Previous studies analysing personality and cannabis use in adult samples suggest
      that cannabis users show significant higher levels of impulsivity, sensation
      seeking and schizotypy. However, there are few studies exploring this
      relationship in adolescence using psychobiological models of personality. Given
      the relevance of identifying individual differences that lead adolescents to
      early cannabis use to prevent future health problems, the present study aimed to
      explore the relationship between age, sex, personality and early cannabis use
      using a psychobiological model of personality in a sample of 415 students (51.8%
      boys) from 12 to 18 years. Chi(2) tests showed significant higher prevalence of
      cannabis use in boys and in the group aged 15-18 years. Multiple analysis of
      variance showed significant higher scores in psychoticism, sensation seeking and
      in all its subscales in cannabis users group, while an interaction with age was
      found for extraversion and neuroticism: cannabis users scored higher than non
      users in the youngest group (12-14 years) but lower in the oldest group in both
      dimensions. Finally, regression analysis showed that narrower traits of sensation
      seeking (experience seeking and disinhibition) were the most associated to early
      cannabis use. Results are discussed in terms of early cannabis users' personality
      profiles and in terms of the self-medication theory.

PMID- 25752727
TI  - Proliferation Determined by Ki-67 Defines Different Pathologic Response to
      Neoadjuvant Trastuzumab-Based Chemotherapy in HER2-Positive Breast Cancer.
AB  - BACKGROUND: This study aimed to assess the role of proliferation measured by Ki
      67 as a predictive factor for pathologic complete response (pCR) to trastuzumab
      based chemotherapy in patients with human epidermal growth factor receptor 2
      (HER2)-positive (HER2(+)) breast cancer (BC). METHODS: A total of 81 patients
      with HER2(+) BC were treated with a sequential schedule consisting of 4 cycles of
      cyclophosphamide (600 mg/m(2)) and doxorubicin (60 mg/m(2)) every 3 weeks,
      followed by 4 cycles of weekly paclitaxel (80 mg/m(2)) or docetaxel (100 mg/m(2))
      every 3 weeks combined with trastuzumab (loading dose of 8 mg/kg and then 6 mg/kg
      every 3 weeks) as neoadjuvant treatment. Histologic subgroups classified by
      hormone receptor (HR) expression and Ki-67 index were 17% HR(+)/Ki-67 >= 50%, 41%
      HR(+)/Ki-67 < 50%, 25% HR-negative (HR(-)) Ki-67 >= 50%, and 17% HR(-)/Ki-67 <
      50%. RESULTS: pCR, defined as the absence of invasive cells in the breast and
      axillary lymph node, was achieved in 33 patients (41%). The median Ki-67
      expression was significantly higher in tumors with pCR (53%) compared with tumors
      without pCR (30%) (P < .001). Receiver operating characteristic (ROC) curve
      methodology suggested that 50% was the optimal Ki-67 cutoff point to best
      identify patients who achieved a pCR. The pCR rate was significantly different
      between histologic subgroups: HR(-)/Ki-67 >= 50% (70%), HR(+)/Ki-67 >= 50% (71%),
      HR(-)/Ki-67 < 50% (22%), and HR(+)/Ki-67 < 50% (18%) (P < .001). A multivariate
      analysis revealed that a Ki-67 marker >= 50% was the only independent predictive
      factor of pCR (P = .003; odds ratio [OR], 0.133; 95% confidence interval [CI],
      0.036-0.5). The median follow-up was 32 months (range, 14-48 months). Patients
      who achieved a pCR had significantly lower recurrence (P = .001) and higher
      overall survival (OS) (P = .013) compared with those who did not. There were no
      statistically significant differences in disease-free survival (DFS) and OS in
      relation to HRs, the Ki-67 marker as a continuous or categorical variable, and
      histologic subgroups. CONCLUSION: Proliferation determined by Ki-67 expression >=
      50% was an independent predictive factor for pCR in patients with HER2(+) BC
      treated with trastuzumab-based chemotherapy.

PMID- 25752728
TI  - Multi-perspective workflow modeling for online surgical situation models.
AB  - INTRODUCTION: Surgical workflow management is expected to enable situation-aware
      adaptation and intelligent systems behavior in an integrated operating room (OR).
      The overall aim is to unburden the surgeon and OR staff from both manual
      maintenance and information seeking tasks. A major step toward intelligent
      systems behavior is a stable classification of the surgical situation from
      multiple perspectives based on performed low-level tasks. MATERIAL AND METHODS:
      The present work proposes a method for the classification of surgical situations
      based on multi-perspective workflow modeling. A model network that interconnects
      different types of surgical process models is described. Various aspects of a
      surgical situation description were considered: low-level tasks, high-level
      tasks, patient status, and the use of medical devices. A study with sixty
      neurosurgical interventions was conducted to evaluate the performance of our
      approach and its robustness against incomplete workflow recognition input.
      RESULTS: A correct classification rate of over 90% was measured for high-level
      tasks and patient status. The device usage models for navigation and
      neurophysiology classified over 95% of the situations correctly, whereas the
      ultrasound usage was more difficult to predict. Overall, the classification rate
      decreased with an increasing level of input distortion. DISCUSSION: Autonomous
      adaptation of medical devices and intelligent systems behavior do not currently
      depend solely on low-level tasks. Instead, they require a more general type of
      understanding of the surgical condition. The integration of various surgical
      process models in a network provided a comprehensive representation of the
      interventions and allowed for the generation of extensive situation descriptions.
      CONCLUSION: Multi-perspective surgical workflow modeling and online situation
      models will be a significant pre-requisite for reliable and intelligent systems
      behavior. Hence, they will contribute to a cooperative OR environment.

PMID- 25752729
TI  - Differing phagocytic capacities of accessory and main olfactory ensheathing cells
      and the implication for olfactory glia transplantation therapies.
AB  - The rodent olfactory systems comprise the main olfactory system for the detection
      of odours and the accessory olfactory system which detects pheromones. In both
      systems, olfactory axon fascicles are ensheathed by olfactory glia, termed
      olfactory ensheathing cells (OECs), which are crucial for the growth and
      maintenance of the olfactory nerve. The growth-promoting and phagocytic
      characteristics of OECs make them potential candidates for neural repair
      therapies such as transplantation to repair the injured spinal cord. However,
      transplanting mixed populations of glia with unknown properties may lead to
      variations in outcomes for neural repair. As the phagocytic capacity of the
      accessory OECs has not yet been determined, we compared the phagocytic capacity
      of accessory and main OECs in vivo and in vitro. In normal healthy animals, the
      accessory OECs accumulated considerably less axon debris than main OECs in vivo.
      Analysis of freshly dissected OECs showed that accessory OECs contained 20% less
      fluorescent axon debris than main OECs. However, when assayed in vitro with
      exogenous axon debris added to the culture, the accessory OECs phagocytosed
      almost 20% more debris than main OECs. After surgical removal of one olfactory
      bulb which induced the degradation of main and accessory olfactory sensory axons,
      the accessory OECs responded by phagocytosing the axon debris. We conclude that
      while accessory OECs have the capacity to phagocytose axon debris, there are
      distinct differences in their phagocytic capacity compared to main OECs. These
      distinct differences may be of importance when preparing OECs for neural
      transplant repair therapies. 

PMID- 25752730
TI  - Alternative splicing of the LIM-homeodomain transcription factor Isl1 in the
      mouse retina.
AB  - Islet-1 (Isl1) is a LIM-homeodomain (LIM-HD) transcription factor that functions
      in a combinatorial manner with other LIM-HD proteins to direct the
      differentiation of distinct cell types within the central nervous system and many
      other tissues. A study of pancreatic cell lines showed that Isl1 is alternatively
      spliced generating a second isoform, Isl1beta, which is missing 23 amino acids
      within the C-terminal region. This study examines the expression of the canonical
      and alternative Isl1 transcripts across other tissues, in particular, within the
      retina, where Isl1 is required for the differentiation of multiple neuronal cell
      types. The alternative splicing of Isl1 is shown to occur in multiple tissues,
      but the relative abundance of Isl1alpha and Isl1beta expression varies greatly
      across them. In most tissues, Isl1alpha is the more abundant transcript, but in
      others the transcripts are expressed equally, or the alternative splice variant
      is dominant. Within the retina, differential expression of the two Isl1
      transcripts increases as a function of development, with dynamic changes in
      expression peaking at E16.5 and again at P10. At the cellular level, individual
      retinal ganglion cells vary in their expression, with a subset of small-to-medium
      sized cells expressing only the alternative isoform. The functional significance
      of the difference in protein sequence between the two Isl1 isoforms was also
      assessed using a luciferase assay, demonstrating that the alternative isoform
      forms a less effective transcriptional complex for activating gene expression.
      These results demonstrate the differential presence of the canonical and
      alternative isoforms of Isl1 amongst retinal ganglion cell classes. As Isl1
      participates in the differentiation of multiple cell types within the CNS, the
      present results support a role for alternative splicing in the establishment of
      cellular diversity in the developing nervous system. 

PMID- 25752731
TI  - Neurite outgrowth in normal and injured primary sensory neurons reveals different
      regulation by nerve growth factor (NGF) and artemin.
AB  - Neurotrophic factors have been intensively studied as potential therapeutic
      agents for promoting neural regeneration and functional recovery after nerve
      injury. Artemin is a member of the glial cell line-derived neurotrophic factor
      (GDNF) family of ligands (GFLs) that forms a signalling complex with GFRalpha3
      and the tyrosine kinase Ret. Systemic administration of artemin in rodents is
      reported to facilitate regeneration of primary sensory neurons following axotomy,
      improve recovery of sensory function, and reduce sensory hypersensitivity that is
      a cause of pain. However, the biological mechanisms that underlie these effects
      are mostly unknown. This study has investigated the biological significance of
      the colocalisation of GFRalpha3 with TrkA (neurotrophin receptor for nerve growth
      factor [NGF]) in the peptidergic type of unmyelinated (C-fibre) sensory neurons
      in rat dorsal root ganglia (DRG). In vitro neurite outgrowth assays were used to
      study the effects of artemin and NGF by comparing DRG neurons that were
      previously uninjured, or were axotomised in vivo by transecting a visceral or
      somatic peripheral nerve. We found that artemin could facilitate neurite
      initiation but in comparison to NGF had low efficacy for facilitating neurite
      elongation and branching. This low efficacy was not increased when a
      preconditioning in vivo nerve injury was used to induce a pro-regenerative state.
      Neurite initiation was unaffected by artemin when PI3 kinase and Src family
      kinase signalling were blocked, but NGF had a reduced effect. 

PMID- 25752732
TI  - Multiple forms of metaplasticity at a single hippocampal synapse during late
      postnatal development.
AB  - Metaplasticity refers to adjustment in the requirements for induction of synaptic
      plasticity based on the prior history of activity. Numerous forms of
      developmental metaplasticity are observed at Schaffer collateral synapses in the
      rat hippocampus at the end of the third postnatal week. Emergence of spatial
      learning and memory at this developmental stage suggests possible involvement of
      metaplasticity in the final maturation of the hippocampus. Three distinct
      metaplastic phenomena are apparent. (1) As transmitter release probability
      increases with increasing age, presynaptic potentiation is reduced. (2)
      Alterations in the composition and channel conductance properties of AMPARs
      facilitate the induction of postsynaptic potentiation with increasing age. (3)
      Low frequency stimulation inhibits subsequent induction of potentiation in
      animals older but not younger than 3 weeks of age. Thus, many forms of plasticity
      expressed at SC-CA1 synapses are different in rats younger and older than 3 weeks
      of age, illustrating the complex orchestration of physiological modifications
      that underlie the maturation of hippocampal excitatory synaptic transmission.
      This review paper describes three late postnatal modifications to synaptic
      plasticity induction in the hippocampus and attempts to relate these metaplastic
      changes to developmental alterations in hippocampal network activity and the
      maturation of contextual learning.

PMID- 25752733
TI  - The importance of atopy on exhaled nitric oxide levels in African American
      children.
AB  - BACKGROUND: For physicians to be maximally effective in managing asthma in
      minority populations, a better understanding of the factors that affect
      fractional exhaled nitric oxide (FeNO) measurements in African Americans is
      needed. OBJECTIVE: To examine demographic, environmental, and physiologic factors
      that influence FeNO measurements in African American children with and without
      asthma. METHODS: A cross-sectional study of 128 African American children aged 7
      to 18 years (44% with asthma) was conducted. FeNO measurements, skin prick tests
      (as a measure of atopy), spirometry, and questionnaire data were obtained from
      all participants. Regression models were constructed after identifying factors
      significantly associated on univariate analysis. RESULTS: Among all study
      participants, the mean FeNO measurement at baseline was 24.4 ppb. Children with
      asthma had a higher level than those without (30.9 vs 19.3 ppb, P = .002). When
      examining all children through logistic regression analysis, an elevated FeNO
      level was significantly associated with atopy, lower spirometric values, and
      current asthma (P < .05 for all). Among asthmatic children, univariate analysis
      revealed that an elevated FeNO level was associated with inhaled corticosteroid
      use, recent respiratory infection, and atopy (P < .05 for all). However, only
      atopy remained significant after regression analysis. For asthmatic and
      nonasthmatic children, FeNO levels were directly correlated with the number of
      positive skin test results. CONCLUSION: In African American children with and
      without asthma, FeNO levels are strongly influenced by atopy. Guidelines for FeNO
      measurements that incorporate atopic status are needed.

PMID- 25752734
TI  - Immunoregulatory and immunostimulatory responses of bacterial lysates in
      respiratory infections and asthma.
AB  - OBJECTIVE: This review focuses on the current understanding of the molecular
      mechanisms of bacterial lysates, evidence of an induction of innate immunity, and
      the interaction with immunoregulators, dendritic cells, and regulatory T cells.
      Clinical relevance is summarized based on the observed mechanisms of action of
      bacterial lysates. DATA SOURCES: Academic Search Complete, CENTRAL, Health
      Source: Nursing/Academic Edition, MEDLINE, and Cochrane databases. STUDY
      SELECTIONS: Three independent researchers focused on primary and secondary end
      points in systematic reviews, meta-analyses, and randomized controlled trials
      using bacterial lysates as a verum group or within a subpopulation of larger
      studies. Interventional and observational studies on novel applications also were
      included. Preclinical studies included murine models focusing on toll-like
      receptors (TLRs) and regulatory T cells and on the relation with asthma and
      respiratory immunity. RESULTS: Bacterial lysates have been observed to induce
      synergistic TLR-2/6- and TLR-9-dependent innate immunity. It has positive
      outcomes in decreasing recurrent respiratory tract infections in childhood and
      adult chronic obstructive pulmonary disease. This class of immunostimulants shows
      some evidence of mitigating infection morbidity in children and decreasing the
      frequency of inflammatory episodes (ie, wheezing exacerbations) in children with
      asthma. Preclinical studies suggest that regulatory T cells can be induced by
      bacterial lysates and might attenuate T-helper cell type 2 allergic responses.
      CONCLUSION: Although successful prevention against all common respiratory
      pathogens is not possible, bacterial lysates seem capable of targeting specific
      immunocompetent cells through pathogen recognition receptor activation. Current
      challenges include clarifying the duality of immunoregulatory and
      immunostimulatory responses in children at risk for allergy. Larger clinical
      trials are required to elicit efficacy in allergy prevention.

PMID- 25752735
TI  - Radiation therapy at compact Compton sources.
AB  - The principle of the compact Compton source is presented briefly. In collision
      with an ultrarelativistic electron bunch a laser pulse is back-scattered as hard
      X-rays. The radiation cone has an opening of a few mrad, and the energy bandwidth
      is a few percent. The electrons that have an energy of the order of a few tens of
      MeV either circulate in storage ring, or are injected to a linac at a frequency
      of 10-100 MHz. At the interaction point the electron bunch collides with the
      laser pulse that has been amplified in a Fabry-Perot resonator. There are several
      machines in design or construction phase, and projected fluxes are 10(12) to
      10(14) photons/s. The flux available at 80 keV from the ThomX machine is compared
      with that used in the Stereotactic Synchrotron Radiation Therapy clinical trials.
      It is concluded that ThomX has the potential of serving as the radiation source
      in future radiation therapy programs, and that ThomX can be integrated in
      hospital environment.

PMID- 25752737
TI  - Broad-range inhibition of enterovirus replication by OSW-1, a natural compound
      targeting OSBP.
AB  - Enteroviruses, e.g., polio-, coxsackie- and rhinoviruses, constitute a large
      genus within the Picornaviridae family of positive-strand RNA viruses and include
      many important pathogens linked to a variety of acute and chronic diseases.
      Despite their huge medical and economic impact, no approved antiviral therapy is
      yet available. Recently, the oxysterol-binding protein (OSBP) was implicated as a
      host factor for enterovirus replication. Here, we investigated the antiviral
      activity of the natural compound OSW-1, a ligand of OSBP that is under
      investigation as an anti-cancer drug. OSW-1 potently inhibited the replication of
      all enteroviruses tested, with IC50 values in the low nanomolar range, acted at
      the genome replication stage and was effective in all tested cell types of three
      different species. Importantly, OSBP overexpression rescued viral replication,
      demonstrating that the antiviral effect of OSW-1 is due to targeting OSBP.
      Together, we here report the anti-enterovirus activity of the natural anti-cancer
      compound OSW-1. 

PMID- 25752736
TI  - The underlying role of posttraumatic stress disorder symptoms in the association
      between intimate partner violence and deliberate self-harm among African American
      women.
AB  - African American women are at heightened risk for intimate partner violence (IPV)
      and its negative consequences, including health-compromising behaviors.
      Deliberate self-harm (DSH) is one clinically-relevant behavior that has been
      understudied among African American women generally and those with exposure to
      IPV in particular. To date, no studies have examined factors that may account for
      the relationship between IPV and DSH. Therefore, the goal of the present study
      was to examine the intercorrelations among IPV (physical, psychological, and
      sexual), PTSD, and DSH history and versatility, and the potentially mediating
      role of PTSD symptoms in the IPV-DSH relation. Participants were 197 African
      American community women currently experiencing IPV. Sixty participants (31%)
      reported a history of DSH. Among participants who reported DSH, there was an
      average endorsement of 2.3 unique forms of deliberate self-harm (i.e., DSH
      versatility). Significant positive associations were detected among physical IPV
      severity, psychological IPV severity, PTSD symptom severity, and DSH history and
      versatility. PTSD symptom severity mediated the relationships between physical
      and psychological IPV severity and DSH history and versatility. Results highlight
      the relevance of PTSD symptoms to DSH and suggest that treatments targeting PTSD
      symptoms may be useful in reducing DSH among IPV-exposed African American women. 

PMID- 25752738
TI  - Intravenous peramivir inhibits viral replication, and leads to bacterial
      clearance and prevention of mortality during murine bacterial co-infection caused
      by influenza A(H1N1)pdm09 virus and Streptococcus pneumoniae.
AB  - INTRODUCTION: Influenza virus infection increases susceptibility to bacterial
      infection and mortality in humans. Although the efficacy of approved intravenous
      peramivir, a neuraminidase (NA) inhibitor, against influenza virus infection has
      been reported, its efficacy against bacterial co-infection, which occurs during
      the period of viral shedding, was not fully investigated. To further understand
      the significance of treatment with peramivir, we assessed the efficacy of
      peramivir against a bacterial co-infection model in mice caused by clinically
      isolated influenza A(H1N1)pdm09 virus and Streptococcus pneumoniae. METHODS: Mice
      were infected with influenza A(H1N1)pdm09. Peramivir was intravenously
      administered after the viral infection. At 2days post viral infection, the mice
      were infected with S. pneumoniae. Peramivir efficacy was measured by the survival
      rates and viral titers, bacterial titers, or proinflammatory cytokine
      concentrations in lung homogenates. RESULTS: Peramivir treatment reduced the
      mortality of mice infected with influenza virus and S. pneumoniae. The survival
      rate in the peramivir-treated group was significantly higher than that in the
      oseltamivir-treated group. Viral titers and proinflammatory cytokine responses in
      the peramivir-treated group were significantly lower than those in the
      oseltamivir-treated group until at 2days post viral infection. Bacterial titer
      was significantly lower in the peramivir-treated group than in the oseltamivir
      treated group at 4days post viral infection. CONCLUSION: These results
      demonstrated that peramivir inhibits viral replication, consequently leading to
      bacterial clearance and prevention of mortality during severe murine bacterial co
      infection, which occurs during the period of viral shedding, with the efficacy of
      peramivir being superior to that of oseltamivir.

PMID- 25752739
TI  - Effect of tyrphostin AG879 on Kv 4.2 and Kv 4.3 potassium channels.
AB  - BACKGROUND AND PURPOSE: A-type potassium channels (IA) are important proteins for
      modulating neuronal membrane excitability. The expression and activity of Kv 4.2
      channels are critical for neurological functions and pharmacological inhibitors
      of Kv 4.2 channels may have therapeutic potential for Fragile X syndrome. While
      screening various compounds, we identified tyrphostin AG879, a tyrosine kinase
      inhibitor, as a Kv 4.2 inhibitor from. In the present study we characterized the
      effect of AG879 on cloned Kv 4.2/Kv channel-interacting protein 2 (KChIP2)
      channels. EXPERIMENTAL APPROACH: To screen the library of pharmacologically
      active compounds, the thallium flux assay was performed on HEK-293 cells
      transiently-transfected with Kv 4.2 cDNA using the Maxcyte transfection system.
      The effects of AG879 were further examined on CHO-K1 cells expressing Kv
      4.2/KChIP2 channels using a whole-cell patch-clamp technique. KEY RESULTS:
      Tyrphostin AG879 selectively and dose-dependently inhibited Kv 4.2 and Kv 4.3
      channels. In Kv 4.2/KChIP2 channels, AG879 induced prominent acceleration of the
      inactivation rate, use-dependent block and slowed the recovery from inactivation.
      AG879 induced a hyperpolarizing shift in the voltage-dependence of the steady
      state inactivation of Kv 4.2 channels without apparent effect on the V1/2 of the
      voltage-dependent activation. The blocking effect of AG879 was enhanced as
      channel inactivation increased. Furthermore, AG879 significantly inhibited the A
      type potassium currents in the cultured hippocampus neurons. CONCLUSION AND
      IMPLICATIONS: AG879 was identified as a selective and potent inhibitor the Kv 4.2
      channel. AG879 inhibited Kv 4.2 channels by preferentially interacting with the
      open state and further accelerating their inactivation.

PMID- 25752741
TI  - Dealing with chemotherapy-related symptoms at home: a qualitative study in adult
      patients with cancer.
AB  - Given that chemotherapy treatments are done mostly in an outpatient setting,
      patients with cancer must deal with treatment-related symptoms mainly at home.
      Evidence suggests that they often feel left alone or unprepared to do so. This
      qualitative study explores how patients deal with chemotherapy-related symptoms
      in their home, which factors and ideas influence their self-management and what
      role professional caregivers play. One-off, semi-structured interviews were held
      with 28 adult patients with cancer being treated with chemotherapy. Using a
      Grounded Theory approach, we cyclically collected and analysed data to come to a
      thorough understanding of the major conceptual themes and their interconnections.
      Dealing with chemotherapy-related symptoms involves a process of experiencing and
      learning how side effects unfold over time and how to deal with them. Patients
      express very personal symptom experiences and symptom-management styles, which
      are shaped by personal factors (e.g. coping with cancer and cancer treatment,
      perceived level of control) and environmental factors (e.g. professionals'
      attitude, information resources). Improving symptom self-management support
      requires active exploration of the personal symptom experience and symptom
      management style. Professional care should be tailored to the patient's
      perspective and should address personal and environmental determinants of their
      behaviour. 

PMID- 25752743
TI  - Paracetamol poisoning in adolescents in an Australian setting: not quite adults.
AB  - OBJECTIVE: To describe and compare the characteristics of paracetamol poisoning
      in adolescent and adult patients. METHOD: Descriptive retrospective case series
      of adolescent (12-17 years) and adult (>18 years) patients presenting to a
      metropolitan hospital network ED, diagnosed with paracetamol poisoning from
      October 2009 to September 2013. RESULTS: There were 220 adolescent (median age 16
      years, 47% treated with acetylcysteine [NAC]) and 647 adult presentations (median
      age 27 years, 42% treated with NAC) for paracetamol poisoning in the study
      period. Adolescent patients were more frequently women (89% vs 76%; odds ratio
      [OR] 2.4; 95% confidence interval [CI] 1.5-3.8) and ingested similar amounts of
      paracetamol (18 g) when requiring NAC treatment. Adolescents were more likely to
      ingest paracetamol as a single agent (53% vs 34%; OR 2.2; 95% CI 1.6-3.0) and
      less likely to ingest compound paracetamol products than adults (18% vs 29%; OR
      0.54; 95% CI 0.36-0.79). Adolescents were less likely to report accidental
      supratherapeutic ingestion of paracetamol (0.02% vs 10%; OR 0.23; 95% CI 0.09
      0.58), or co-ingestion of prescription medications (25% vs 43%; OR 0.4; 95% CI
      0.31-0.62). Adolescents had more frequent histamine release reactions to NAC than
      adults (17% vs 8%; OR 2.3; 95% CI 1.2-4.5). No cases required liver
      transplantation or resulted in death. CONCLUSION: Adolescents ingested comparable
      amounts of paracetamol to adults, when presenting with deliberate self-poisoning.
      However, there were significant differences in co-ingested medications and the
      reason for ingestion of paracetamol. Histamine reactions to NAC were more common
      in adolescents; however, most were mild. Overall, outcome was favourable in both
      cohorts.

PMID- 25752742
TI  - Migration of blood cells to beta-amyloid plaques in Alzheimer's disease.
AB  - Alzheimer's disease (AD) is a neurodegenerative disease that leads to the
      progressive deterioration of cognitive and memory functions. The deposition of
      extracellular beta-amyloid (Abeta) senile plaques and intracellular tau
      neurofibrillary tangles are considered the cardinal pathological hallmarks of AD,
      however, accumulating evidence indicates that immune cells may also play an
      important role in disease pathogenesis. Among these immune cells, blood-derived
      cells and their infiltration into the CNS towards Abeta plaques have been
      implicated in therapeutic strategies against AD. Here, we review the current
      literature on blood cell migration into the AD brain and the important players
      involved in this selective migration towards Abeta plaques. 

PMID- 25752740
TI  - Health related quality of life of women in TEACH, a randomised placebo controlled
      adjuvant trial of lapatinib in early stage Human Epidermal Growth Factor Receptor
      (HER2) overexpressing breast cancer.
AB  - BACKGROUND: To evaluate health related quality of life (HRQOL) in TEACH, a phase
      III randomized placebo controlled trial of 12 months of adjuvant lapatinib in
      HER2 positive (HER2+) early breast cancer which demonstrated marginal benefit in
      disease-free survival. METHODS: Women on TEACH completed the Short Form 36-item
      health survey (version2; SF-36v2) at the baseline, six and 12 months after
      therapy initiation and six monthly thereafter. Mean changes were compared between
      treatment groups for two summary measures (Physical and Mental Component Summary
      scores; PCS and MCS) and eight domain measures (physical functioning, role
      physical, bodily pain, general health, vitality, social functioning, role
      emotional and mental health), and in patients discontinuing therapy. A five-point
      change was deemed a Minimally Clinically Important Difference (MCID). Response
      analysis compared the proportion of patients demonstrating a MCID in HRQOL, and a
      regression analysis identified predictors of worsening HRQOL. FINDINGS: 3074
      (97%) subjects completed baseline SF-36v2. During the initial 12 months, summary
      SF-36v2 scores decreased in both arms but did not reach Minimally Clinically
      Important Difference (MCID) despite significant incidences of diarrhoea and rash
      in lapatinib treated patients. At six months, women receiving lapatinib had more
      significant reductions (p < 0.01 versus placebo) in social functioning. Early
      treatment discontinuations were more frequent on lapatinib (32% versus 18%), and
      were associated with more substantial decrements of HRQOL in both arms. For those
      discontinuing primarily due to adverse events, decrements in HRQOL reached MCID
      in Mental Summary scores (MCS) only. Lower baseline HRQOL was a significant
      predictor of worsening HRQOL (p < 0.05). INTERPRETATION: Despite frequent but
      usually mild toxicities, adjuvant lapatinib is not associated with clinically
      significant decreases in overall HRQOL. These placebo-controlled results may also
      help to inform physicians and patients using lapatinib in metastatic HER2
      positive breast cancer. FUNDING: GlaxoSmithKline. The AVON Foundation NY
      supported PEG, DF and BM and The Friends of the Mater Foundation supported FB.

PMID- 25752744
TI  - The effects of survey modality on adolescents' responses to alcohol use items.
AB  - BACKGROUND: We examined differences in response to self-reported alcohol use
      items by survey mode, whether self-report differences were the result of modality
      effects or self-selection, and whether these differences varied across the
      treatment and control arms of a preventative intervention trial. METHODS: Data
      from an existing alcohol prevention trial were used to estimate the effect of
      survey modality on adolescent's self-reported alcohol use at ages 17 to 18.
      Estimates were derived from regression models controlling for self-reported
      alcohol use during 8th grade, measured using a single survey modality, as well as
      time invariant selection factors. RESULTS: No statistically significant survey
      modality effects were found. No differential effects of survey modality were
      observed by assigned intervention group. CONCLUSIONS: We provide initial evidence
      that adolescent alcohol prevention trials may use multiple survey modalities when
      necessary to increase response rates without harming interpretation of
      intervention effects.

PMID- 25752745
TI  - Epicardial adipose tissue: a benign consequence of obesity?

PMID- 25752746
TI  - Inter-hemispheric wave propagation failures in traumatic brain injury are
      indicative of callosal damage.
AB  - Approximately 3.2-5.3 million Americans live with the consequences of a traumatic
      brain injury (TBI), making TBI one of the most common causes of disability in the
      world. Visual deficits often accompany TBI but physiological and anatomical
      evidence for injury in mild TBI is lacking. Axons traversing the corpus callosum
      are particularly vulnerable to TBI. Hemifield representations of early visual
      areas are linked by bundles of fibers that together cross the corpus callosum
      while maintaining their topographic relations. Given the increased vulnerability
      of the long visual axons traversing the corpus callosum, we hypothesized that
      inter-hemispheric transmission for vision will be impaired following mild TBI.
      Using the travelling wave paradigm (Wilson, Blake, & Lee 2001), we measured inter
      hemispheric transmission in terms of both speed and propagation failures in 14
      mild TBI patients and 14 age-matched controls. We found that relative to intra
      hemispheric waves, inter-hemispheric waves were faster and that the inter
      hemispheric propagation failures were more common in TBI patients. Furthermore,
      the transmission failures were topographically distributed, with a bias towards
      greater failures for transmission across the upper visual field. We discuss the
      results in terms of increased local inhibition and topographically-selective
      axonal injury in mild TBI.

PMID- 25752747
TI  - Designing clinical trials for amblyopia.
AB  - Randomized clinical trial (RCT) study design leads to one of the highest levels
      of evidence, and is a preferred study design over cohort studies, because
      randomization reduces bias and maximizes the chance that even unknown confounding
      factors will be balanced between treatment groups. Recent randomized clinical
      trials and observational studies in amblyopia can be taken together to formulate
      an evidence-based approach to amblyopia treatment, which is presented in this
      review. When designing future clinical studies of amblyopia treatment, issues
      such as regression to the mean, sample size and trial duration must be
      considered, since each may impact study results and conclusions. 

PMID- 25752749
TI  - Setting benchmark revision rates for total hip replacement: analysis of registry
      evidence.
AB  - OBJECTIVE: To compare 10 year revision rates for frequently used types of primary
      total hip replacement to inform setting of a new benchmark rate in England and
      Wales that will be of international relevance. DESIGN: Retrospective cohort
      study. SETTING: National Joint Registry. PARTICIPANTS: 239 000 patient records.
      MAIN OUTCOME MEASURES: Revision rates for five frequently used types of total hip
      replacement that differed according to bearing surface and fixation mode,
      encompassing 62% of all primary total hip replacements in the National Joint
      Registry for England and Wales. Revision rates were compared using Kaplan-Meier
      and competing risks analyses, and five and 10 year rates were estimated using
      well fitting parametric models. RESULTS: Estimated revision rates at 10 years
      were 4% or below for four of the five types of total hip replacement
      investigated. Rates differed little according to Kaplan-Meier or competing risks
      analysis, but differences between prosthesis types were more substantial.
      Cemented prostheses with ceramic-on-polyethylene bearing surfaces had the lowest
      revision rates (1.88-2.11% at 10 years depending on the method used), and
      cementless prostheses with ceramic-on-ceramic bearing surfaces had the highest
      revision rates (3.93-4.33%). Men were more likely to receive revision of total
      hip replacement than were women, and this difference was statistically
      significant for four of the five prosthesis types. CONCLUSIONS: Ten year revision
      rate estimates were all less than 5%, and in some instances considerably less.
      The results suggest that the current revision rate benchmark should be at least
      halved from 10% to less than 5% at 10 years. This has implications for benchmarks
      internationally.

PMID- 25752750
TI  - Field and chirality effects on electrochemical charge transfer rates: spin
      dependent electrochemistry.
AB  - This work examines whether electrochemical redox reactions are sensitive to the
      electron spin orientation by examining the effects of magnetic field and
      molecular chirality on the charge transfer process. The working electrode is
      either a ferromagnetic nickel film or a nickel film that is coated with an
      ultrathin (5-30 nm) gold overlayer. The electrode is coated with a self-assembled
      monolayer that immobilizes a redox couple containing chiral molecular units,
      either the redox active dye toluidine blue O with a chiral cysteine linking unit
      or cytochrome c. By varying the direction of magnetization of the nickel, toward
      or away from the adsorbed layer, we demonstrate that the electrochemical current
      depends on the orientation of the electrons' spin. In the case of cytochrome c,
      the spin selectivity of the reduction is extremely high, namely, the reduction
      occurs mainly with electrons having their spin-aligned antiparallel to their
      velocity. 

PMID- 25752748
TI  - The pluripotent regulatory circuitry connecting promoters to their long-range
      interacting elements.
AB  - The mammalian genome harbors up to one million regulatory elements often located
      at great distances from their target genes. Long-range elements control genes
      through physical contact with promoters and can be recognized by the presence of
      specific histone modifications and transcription factor binding. Linking
      regulatory elements to specific promoters genome-wide is currently impeded by the
      limited resolution of high-throughput chromatin interaction assays. Here we apply
      a sequence capture approach to enrich Hi-C libraries for >22,000 annotated mouse
      promoters to identify statistically significant, long-range interactions at
      restriction fragment resolution, assigning long-range interacting elements to
      their target genes genome-wide in embryonic stem cells and fetal liver cells. The
      distal sites contacting active genes are enriched in active histone modifications
      and transcription factor occupancy, whereas inactive genes contact distal sites
      with repressive histone marks, demonstrating the regulatory potential of the
      distal elements identified. Furthermore, we find that coregulated genes cluster
      nonrandomly in spatial interaction networks correlated with their biological
      function and expression level. Interestingly, we find the strongest gene
      clustering in ES cells between transcription factor genes that control key
      developmental processes in embryogenesis. The results provide the first genome
      wide catalog linking gene promoters to their long-range interacting elements and
      highlight the complex spatial regulatory circuitry controlling mammalian gene
      expression. 

PMID- 25752751
TI  - A phase I study of bendamustine, lenalidomide and rituximab in relapsed and
      refractory lymphomas.
AB  - Many patients with non-Hodgkin (NHL) or Hodgkin lymphoma (HL) relapse or are
      refractory to initial therapy and require additional options. Bendamustine (B),
      lenalidomide (L) and rituximab (R) each have activity in this setting. This study
      was performed to determine the safety of BLR and its optimal phase II dose.
      Patients with NHL or HL failing standard therapies received B (90 mg/m(2)  days
      1, 2 every 28 days), and L (escalating from 5 mg 21/28 days) for six cycles,
      followed by 6 months of L. At the highest dose R 375 mg/m(2) on day one of each
      cycle was added for patients with B-NHL. Histologies included diffuse large B
      cell lymphoma (DLBCL, 11), marginal zone lymphoma (3), HL (2), and one each of
      transformed follicular lymphoma, Sezary syndrome, Waldenstrom macroglobulinaemia
      and mantle cell lymphoma. Neutropenia was the most common grade 3 and 4 toxicity,
      but no maximum tolerated dose was identified. Of 20 patients, seven responded
      (35%), including four complete remissions, with five unmaintained responses from
      28+ to 37+ months, including 2 DLBCL. BR with 20 mg l at, 21/28 days achieved
      durable responses; however, in light of its modest activity, and the availability
      of newer targeted therapies, the future of BLR is uncertain. 

PMID- 25752752
TI  - Attitudes of Australian neonatologists to resuscitation of extremely preterm
      infants.
AB  - AIM: We aimed to investigate how Australian neonatologists made decisions when
      incompetent patients of different ages needed resuscitation. METHODS: A survey
      including vignettes of eight incompetent patients requiring resuscitation was
      sent to 140 neonatologists. Patients ranged from a very preterm infant to 80
      years old. While some had existing impairments, all faced risk of death or
      neurological sequelae. Respondents indicated whether they would resuscitate,
      whether they believed resuscitation was in the patients' best interests, whether
      they would want intervention for a family member and whether they would comply
      with families' wishes to withhold resuscitation. They were also asked how they
      would rank the eight patients in a triage situation. RESULTS: Seventy-eight per
      cent of specialists completed the survey. The majority of respondents gave
      priority to the resuscitation of children over adults. Less than 40% would agree
      to withhold resuscitation at families' request for all children except for the
      preterm infant, where 96% would comply with families' wishes to withhold
      intensive care despite 77% believing resuscitation to be in the infant's best
      interest. CONCLUSION: This study found inconsistencies between physicians'
      perceptions of the patient's best interest regarding resuscitation and their
      willingness to comply with families' wishes to withhold resuscitation and give
      comfort care. Accepting a family's refusal of resuscitation was more marked for
      the premature infant, even among respondents who thought that resuscitation was
      in the patient's best interest. These findings are consistent with other
      international studies.

PMID- 25752753
TI  - Review article: the safety of therapeutic drugs in male inflammatory bowel
      disease patients wishing to conceive.
AB  - BACKGROUND: Many therapeutic drugs are used by patients with inflammatory bowel
      disease, often around the time of conception. The pregnancy outcomes of males and
      females exposed to these therapeutics needs to be examined and this information
      is necessary to counsel patients appropriately. AIM: To review the literature
      describing male infertility and inflammatory bowel disease to educate
      practitioners of the impact of inflammatory bowel disease on male reproduction
      and the impact of therapeutics on pregnancy outcomes. METHODS: We performed a
      PubMed search using the search terms 'male infertility,' 'Crohn's disease,'
      'inflammatory bowel disease,' 'ulcerative colitis,' 'ciprofloxacin AND
      infertility,' 'metronidazole AND infertility,' 'sulfasalazine AND infertility,'
      'azathioprine AND infertility,' 'methotrexate AND infertility,' 'ciclosporin AND
      infertility,' 'corticosteroids AND infertility,' 'infliximab AND male fertility,'
      'infliximab AND infertility,' 'infliximab AND foetus,' 'infliximab AND paternal
      exposure' and 'infliximab AND sperm.' References from selected papers were
      reviewed and used if relevant. RESULTS: Over half of male patients with IBD have
      some degree of infertility, compared to 8-17% of the general population. Semen
      parameters including total count, motility and morphology may be adversely
      affected by therapeutics. IBD medications in males do not increase foetal risk
      with the possible exception of azathioprine and mercaptopurine; however,
      increased foetal risk is seen in other drugs if taken by female patients.
      CONCLUSIONS: It is recognised that male infertility is often impacted with
      therapeutic drugs used to treat inflammatory bowel disease; however, the effects
      of the paternal drug exposure at the time of conception and exposure in utero
      should be considered to counsel patients appropriately.

PMID- 25752754
TI  - Integrated analysis of pediatric glioblastoma reveals a subset of biologically
      favorable tumors with associated molecular prognostic markers.
AB  - Pediatric glioblastoma (pedGBM) is amongst the most common malignant brain tumors
      of childhood and carries a dismal prognosis. In contrast to adult GBM, few
      molecular prognostic markers for the pediatric counterpart have been established.
      We, therefore, investigated the prognostic significance of genomic and epigenetic
      alterations through molecular analysis of 202 pedGBM (1-18 years) with
      comprehensive clinical annotation. Routinely prepared formalin-fixed paraffin
      embedded tumor samples were assessed for genome-wide DNA methylation profiles,
      with known candidate genes screened for alterations via direct sequencing or
      FISH. Unexpectedly, a subset of histologically diagnosed GBM (n = 40, 20 %)
      displayed methylation profiles similar to those of either low-grade gliomas or
      pleomorphic xanthoastrocytomas (PXA). These tumors showed a markedly better
      prognosis, with molecularly PXA-like tumors frequently harboring BRAF V600E
      mutations and 9p21 (CDKN2A) homozygous deletion. The remaining 162 tumors with
      pedGBM molecular signatures comprised four subgroups: H3.3 G34-mutant (15 %),
      H3.3/H3.1 K27-mutant (43 %), IDH1-mutant (6 %), and H3/IDH wild-type (wt) GBM (36
      %). These subgroups were associated with specific cytogenetic aberrations, MGMT
      methylation patterns and clinical outcomes. Analysis of follow-up data identified
      a set of biomarkers feasible for use in risk stratification: pedGBM with any
      oncogene amplification and/or K27M mutation (n = 124) represents a particularly
      unfavorable group, with 3-year overall survival (OS) of 5 %, whereas tumors
      without these markers (n = 38) define a more favorable group (3-year OS ~70
      %).Combined with the lower grade-like lesions, almost 40 % of pedGBM cases had
      distinct molecular features associated with a more favorable outcome. This
      refined prognostication method for pedGBM using a molecular risk algorithm may
      allow for improved therapeutic choices and better planning of clinical trial
      stratification for this otherwise devastating disease.

PMID- 25752755
TI  - Marital Discord and Suicidal Outcomes in a National Sample of Married
      Individuals.
AB  - Suicide is the tenth leading cause of death in the United States, with an average
      of 105 suicides committed daily. The association between marital discord and 12
      month prevalence of suicidal ideation and suicide attempt was studied in a
      population-based sample of married adults (N = 1,384). Marital discord was
      significantly and positively associated with suicidal ideation and suicide
      attempt, and these associations remained significant when controlling for
      demographics and 12-month prevalence of mood, anxiety, and substance use
      disorders. Results suggest that marital discord is an important correlate of
      suicidal outcomes and may be important to target in preventing and treating
      suicide.

PMID- 25752757
TI  - Radiation exposure of an anaesthesiologist in catheterisation and
      electrophysiological cardiac procedures.
AB  - Sometimes, cardiac catheterisation and electrophysiological procedures,
      diagnostic and interventional, require an anaesthesiological support. The
      anaesthesiologist receives radiation doses depending on various factors, such as
      type of procedure and exposure modality, anaesthesiological technique, individual
      protective devices and operator experience. The aim of this study was to
      investigate the dose per procedure, the exposure inhomogeneity and the effective
      dose, E, of a senior anaesthesiologist in the haemodynamic laboratory of Ospedali
      Riuniti, Bergamo. The dose monitoring was routinely performed with sets of
      several thermoluminescent dosemeters and an electronic personal dosemeter. The
      study covered 300 consecutive procedures over 1 y. The anaesthesiologist wore a
      protective apron, a thyroid collar and glasses (0.5 mm lead-equivalent). 

PMID- 25752756
TI  - Impact of weight bias and stigma on quality of care and outcomes for patients
      with obesity.
AB  - The objective of this study was to critically review the empirical evidence from
      all relevant disciplines regarding obesity stigma in order to (i) determine the
      implications of obesity stigma for healthcare providers and their patients with
      obesity and (ii) identify strategies to improve care for patients with obesity.
      We conducted a search of Medline and PsychInfo for all peer-reviewed papers
      presenting original empirical data relevant to stigma, bias, discrimination,
      prejudice and medical care. We then performed a narrative review of the existing
      empirical evidence regarding the impact of obesity stigma and weight bias for
      healthcare quality and outcomes. Many healthcare providers hold strong negative
      attitudes and stereotypes about people with obesity. There is considerable
      evidence that such attitudes influence person-perceptions, judgment,
      interpersonal behaviour and decision-making. These attitudes may impact the care
      they provide. Experiences of or expectations for poor treatment may cause stress
      and avoidance of care, mistrust of doctors and poor adherence among patients with
      obesity. Stigma can reduce the quality of care for patients with obesity despite
      the best intentions of healthcare providers to provide high-quality care. There
      are several potential intervention strategies that may reduce the impact of
      obesity stigma on quality of care. 

PMID- 25752760
TI  - Evidence-based guidelines for the management of hypertension in children with
      chronic kidney disease.
AB  - Hypertension is common in children with chronic kidney disease and early evidence
      suggests that it is a modifiable risk factor for renal and cardiovascular
      outcomes. Recommendations for blood pressure management in children with chronic
      kidney disease can be found in various clinical practice guidelines including the
      4th Task Force Report, the European Society of Hypertension pediatric
      recommendations, and the National Kidney Foundation Kidney Disease Outcomes
      Quality Initiative (K/DOQI) and Kidney Disease: Improving Global Outcomes (KDIGO)
      guidelines for the management of blood pressure in chronic kidney disease.
      Unfortunately, as pediatric trial evidence is limited, there are discrepancies in
      the recommendations that may lead to inconsistent clinical care and practice
      variation. This article reviews the strength of evidence behind each of the
      clinical practice guideline recommendations regarding blood pressure assessment,
      treatment targets, and first-line antihypertensive medications. The benefits and
      cautions of use of clinical practice guidelines are described with emphasis on
      the importance of reading beyond the summary statements. 

PMID- 25752761
TI  - A complicated case of atypical hemolytic uremic syndrome with frequent relapses
      under eculizumab.
AB  - BACKGROUND: Atypical hemolytic uremic syndrome (aHUS) is a form of thrombotic
      microangiopathy characterized by uncontrolled activation of the alternative
      complement pathway with consecutive generation of the terminal complement
      complex. Mortality is increased, particularly in the first year of the disease.
      Therapeutic options include plasma therapy and terminal complement blockade using
      the anti-C5 monoclonal antibody eculizumab. Eculizumab prevents activation of the
      terminal sequence of the complement cascade and formation of the potentially
      lytic terminal complement complex (C5b-9). CASE-DIAGNOSIS/TREATMENT: We report a
      3-year-old boy with aHUS due to a novel heterozygous truncating complement Factor
      H mutation in combination with other changes known to be associated with an
      increased risk for aHUS. Despite eculizumab treatment and maximal suppression of
      the classical and alternative complement pathways, C3d and sC5b-9 remained
      consistently elevated and the patient showed repeated relapses. CONCLUSIONS: Not
      every patient with aHUS and uncontrolled complement activation shows optimal
      therapeutic response to eculizumab with the recommended or even increased dosing
      regimen. Reliable outcome measures to determine the efficacy of treatment have to
      be defined.

PMID- 25752759
TI  - Viral-associated glomerulopathies in children.
AB  - Viral infections associate temporally with the onset of many glomerular diseases,
      particularly in children. In other cases of glomerulonephritis, when infection is
      clinically silent, viral syndromes can still be implicated as a trigger. However,
      strong evidence for viral causality in most glomerular disease is still lacking.
      While numerous case reports in children document the occurrence of specific forms
      of glomerular disease after seroconversion to a wide range of viruses, relatively
      few reports provide pathologic evidence of viral infection associated with
      glomerular lesions on kidney biopsy. Strong associations between hepatitis
      viruses and glomerular injury have been acknowledged in adults, but hepatitis C
      virus appears not to be an etiology in children. In the context of treating
      glomerular diseases, when diagnosed, the treatment of hepatitis B virus,
      cytomegalovirus and human immunodeficiency virus in children with
      membranoproliferative, membranous and collapsing glomerulopathy plays an
      important role. Otherwise, there is no evidence suggesting that the
      identification of a viral infection in a child with glomerulopathy should change
      the management of the infection or the glomerulonephritis. Therefore, additional
      research into this topic is very much needed. 

PMID- 25752758
TI  - EURADOS strategic research agenda: vision for dosimetry of ionising radiation.
AB  - Since autumn 2012, the European Radiation Dosimetry Group (EURADOS) has been
      developing its Strategic Research Agenda (SRA), which is intended to contribute
      to the identification of future research needs in radiation dosimetry in Europe.
      The present article summarises-based on input from EURADOS Working Groups (WGs)
      and Voting Members-five visions in dosimetry and defines key issues in dosimetry
      research that are considered important for the next decades. The five visions
      include scientific developments required towards (a) updated fundamental dose
      concepts and quantities, (b) improved radiation risk estimates deduced from
      epidemiological cohorts, (c) efficient dose assessment for radiological
      emergencies, (d) integrated personalised dosimetry in medical applications and
      (e) improved radiation protection of workers and the public. The SRA of EURADOS
      will be used as a guideline for future activities of the EURADOS WGs. A detailed
      version of the SRA can be downloaded as a EURADOS report from the EURADOS website
      (www.eurados.org). 

PMID- 25752762
TI  - Lisdexamfetamine for binge eating disorder in adults: a systematic review of the
      efficacy and safety profile for this newly approved indication - what is the
      number needed to treat, number needed to harm and likelihood to be helped or
      harmed?
AB  - OBJECTIVE: To describe the efficacy and safety of lisdexamfetamine dimesylate
      (LDX) for the treatment of binge eating disorder (BED). DATA SOURCES: The pivotal
      registration trials were accessed by querying
      http://www.ncbi.nlm.nih.gov/pubmed/, http://www.clinicaltrials.gov and
      http://www.clinicaltrialsregister.eu for the search terms 'lisdexamfetamine' and
      'binge', and by also querying the Web of Science (Thomson Reuters) and Embase
      (Elsevier) commercial databases, and by asking the manufacturer for copies of
      posters presented at congresses. Product labelling provided additional
      information. STUDY SELECTION: All available clinical reports of studies were
      identified. DATA EXTRACTION: Descriptions of the principal results and
      calculation of number needed to treat (NNT) and number needed to harm (NNH) for
      relevant dichotomous outcomes were extracted from the available study reports and
      other sources of information. DATA SYNTHESIS: LDX is a central nervous system
      stimulant indicated for the treatment of moderate to severe BED. The recommended
      dose range is 50-70 mg/day. Approval for the treatment of BED was based on a
      clinical development programme that included an 11-week Phase II proof-of
      concept, placebo-controlled study, testing fixed doses of LDX 30, 50 and 70
      mg/day, and two 12-week Phase III placebo-controlled studies examining LDX 50-70
      mg/day. Statistically significant reductions in binge eating days/week, the
      primary outcome measure, were observed for LDX doses of 50 and 70 mg/day, with
      effect sizes in the Phase III trials ranging from 0.83 to 0.97. The pooled NNT
      for response across all trials (as defined by a Clinical Global Impressions
      Improvement score of 'very much improved' or 'much improved') for LDX vs. placebo
      was 3 (95% CI 3-4), and NNT for remission (as defined by 4-week cessation of
      binge eating) for LDX vs. placebo was 4 (95% CI 4-6). Reductions in weight ranged
      between 5.2% and 6.25% for LDX 50 or 70 mg/day. Discontinuation rates because of
      adverse events (AEs) were low; NNH for discontinuation because of an AE for LDX
      vs. placebo was 44 (95% CI 23-1971). The most commonly encountered AEs (incidence
      >= 10% and greater than the rate for placebo) were dry mouth, decreased appetite,
      insomnia and headache, with NNH values vs. placebo of 4 (95% CI 3-5), 11 (95% CI
      8-17), 11 (95% CI 8-18) and 19 (95% CI 11-75), respectively. CONCLUSIONS: LDX is
      the first pharmacological agent that has received regulatory approval for the
      treatment of BED. LDX 50 or 70 mg/day significantly reduced BED symptoms as
      measured by the number of binge eating days per week. Effect sizes were highly
      robust. Pending clinical trials include a long-term study examining maintenance
      of efficacy.

PMID- 25752763
TI  - Expression of Receptors for Pituitary-Type Growth Hormone-Releasing Hormone
      (pGHRH-R) in Human Papillary Thyroid Cancer Cells: Effects of GHRH Antagonists on
      Matrix Metalloproteinase-2.
AB  - Papillary thyroid cancer (PTC) is the most prevalent of all endocrine cancers. In
      recent studies, the presence of receptors for pituitary-type growth hormone
      releasing hormone (pGHRH-R) has been demonstrated in various human cancers,
      including human prostate, brain, and other cancer lines. Thyroid malignancies,
      however, have not yet been investigated in this regard. In this study, we found
      that pGHRH-R and its functional splice variant, SV1, are present in normal
      thyroid and PTC cells. We also treated seven normal and PTC tumor thyroid cells
      in vitro with a GHRH antagonist, MIA-602, to compare its anti-proliferation and
      anti-invasion potential against vehicle-treated cells. We found that treatment
      with GHRH antagonist increases the expression of SV1 and pGHRH-R in tumor cells
      compared to tumor cells exposed to vehicle only, a response which may alter the
      sensitivity of signaling kinases within the cells. GHRH antagonist treatment of
      tumor cells also reduced activity of the tumor invasion marker, matrix
      metalloproteinase (MMP)-2, compared to tumor cells exposed to vehicle only. The
      expression of pGHRH-R and SV1, as well as MMP-2 activity, in normal thyroid cells
      remained unaffected by GHRH antagonist treatment. Similarly, cell proliferation
      rates for tumor or normal thyroid cells were not affected by GHRH antagonist
      treatment. Our findings have important implications for the therapeutic use of
      GHRH antagonist in cases of aggressive PTC refractory to conventional treatment
      modalities, and in which protein expression and MMP-2 activity in normal thyroid
      tissue is left unaltered. 

PMID- 25752764
TI  - An SH2 domain model of STAT5 in complex with phospho-peptides define "STAT5
      Binding Signatures".
AB  - The signal transducer and activator of transcription 5 (STAT5) is a member of the
      STAT family of proteins, implicated in cell growth and differentiation. STAT
      activation is regulated by phosphorylation of protein monomers at conserved
      tyrosine residues, followed by binding to phospho-peptide pockets and subsequent
      dimerization. STAT5 is implicated in the development of severe pathological
      conditions, including many cancer forms. However, nowadays a few STAT5 inhibitors
      are known, and only one crystal structure of the inactive STAT5 dimer is publicly
      available. With a view to enabling structure-based drug design, we have: (1)
      analyzed phospho-peptide binding pockets on SH2 domains of STAT5, STAT1 and
      STAT3; (2) generated a model of STAT5 bound to phospho-peptides; (3) assessed our
      model by docking against a class of known STAT5 inhibitors (Muller et al. in
      ChemBioChem 9:723-727, 2008); (4) used molecular dynamics simulations to optimize
      the molecular determinants responsible for binding and (5) proposed unique
      "Binding Signatures" of STAT5. Our results put in place the foundations to
      address STAT5 as a target for rational drug design, from sequence, structural and
      functional perspectives. 

PMID- 25752765
TI  - Vaginal Lactobacillus gasseri CMUL57 can inhibit herpes simplex type 2 but not
      Coxsackievirus B4E2.
AB  - This study aimed at demonstrating the antiviral activity of Lactobacillus gasseri
      CMUL57 (L. gasseri CMUL57), L. acidophilus CMUL67 and L. plantarum CMUL140
      against herpes simplex type 2 (HSV-2) and Coxsackievirus B4E2 (CVB4E2), which are
      enveloped and naked viruses, respectively. These lactobacilli were non-cytotoxic
      and were able to reduce the cytopathic effect induced by HSV-2 in Vero cell
      monolayers. However, lactobacilli were not active against CVB4E2. Tested
      lactobacilli displayed anti-HSV-2 activity when they were co-incubated with the
      virus prior to inoculating the mixture to Vero cell monolayers. The detection of
      HSV-2 DNA by PCR in pellets of bacteria/virus mixtures let us to hypothesize that
      anti-HSV-2 activity of lactobacilli resulted from the viruses' entrapment. This
      study showed the capabilities of vaginal lactobacilli to inhibit enveloped
      viruses such as HSV-2. 

PMID- 25752766
TI  - Mussel-inspired surface modification of magnetic@graphite nanosheets composite
      for efficient Candida rugosa lipase immobilization.
AB  - By the facile adhesion way, the novel composite complex by polydopamine (PDA) and
      magnetic graphite nanosheets (Fe3O4@GNSs) has been successfully synthesized. The
      resulting composite was characterized by means of scanning electron microscopy,
      transmission electron microscopy, Fourier transform infrared spectra, and Raman
      spectra, X-ray diffraction, X-ray photoelectron spectroscopy, and vibrating
      sample magnetometry. Meanwhile, the PDA functionalized Fe3O4@GNSs (Fe3O4@GNSs
      PDA) was applied for Candida rugosa lipase (CRL) immobilization covalently
      without any toxic coupling agent. Combining the superior physical properties and
      chemical stability of Fe3O4@GNSs and the well biocompatibility, functional
      characteristics of PDA, the Fe3O4@GNSs-PDA composite displayed several
      advantages, including the high enzyme capacity, enzyme activity and stability and
      a decrease in enzyme loss. Our work demonstrated that the mussel-inspired
      Fe3O4@GNSs can be extended to many other applications such as biocatalytic,
      genetic and industrial. 

PMID- 25752768
TI  - A comparison between the principal stress direction and collagen fiber
      orientation in coronary atherosclerotic plaque fibrous caps.
AB  - The rupture of coronary atherosclerotic plaque fibrous caps has been associated
      with acute myocardial infarctions. Collagen fibers, the main structural component
      of vascular tissue, have been observed to change orientation and align themselves
      with the principal stress direction. This study compared the principal stress
      direction in stenosed coronary arteries obtained from 3D fluid-structure
      interaction simulations to the orientation of collagen fibers in the fibrous cap
      of human specimens. The principal stress direction at the peak of the stenosis
      was found to be axially oriented and correlated well with the determined
      orientation of the collagen fibers in the fibrous cap specimens. 

PMID- 25752769
TI  - Correlation analysis of laser Doppler flowmetry signals: a potential non-invasive
      tool to assess microcirculatory changes in diabetes mellitus.
AB  - Measurement and analysis of microcirculation is vital in assessing local and
      systemic tissue health. Changes in microvascular perfusion if detected can
      provide information on the development of various related diseases. Laser Doppler
      blood flowmetry (LDF) provides a non-invasive real-time measurement of cutaneous
      blood perfusion. LDF signals possess fractal nature that represents the
      correlation in the successive signal elements. Changes in the correlation of flow
      and its associated parameters could be used as a tool in differentiating the
      ailments at different stages or assessing the treatment effectiveness of a
      particular ailment. Spectral domain analysis of LDF signals reveals five
      characteristic frequency peaks corresponding to local and central regulatory
      mechanisms of the human body, namely metabolic, neurogenic, myogenic,
      respiration, and heart rate. This paper investigates the changes in the fractal
      nature and constituent frequency bands of laser Doppler signals in diabetic and
      healthy control subjects acquired from the glabrous skin of the foot so as to
      provide an assessment of microcirculatory dynamics. As a pilot study, it was
      attempted on a set of healthy control and diabetic volunteers, and the obtained
      results indicate that fractal nature of LDF signals is less in diabetic subjects
      compared to the healthy control. The wavelet analysis carried out on the set of
      signals reveals the dynamics of blood flow which may have led to the difference
      in correlation results. 

PMID- 25752767
TI  - Peptidoglycan recognition protein-peptidoglycan complexes increase
      monocyte/macrophage activation and enhance the inflammatory response.
AB  - Peptidoglycan recognition proteins (PGRP) are pattern recognition receptors that
      can bind or hydrolyse peptidoglycan (PGN). Four human PGRP have been described:
      PGRP-S, PGRP-L, PGRP-Ialpha and PGRP-Ibeta. Mammalian PGRP-S has been implicated
      in intracellular destruction of bacteria by polymorphonuclear cells, PGRP-Ialpha
      and PGRP-Ibeta have been found in keratinocytes and epithelial cells, and PGRP-L
      is a serum protein that hydrolyses PGN. We have expressed recombinant human PGRP
      and observed that PGRP-S and PGRP-Ialpha exist as monomer and disulphide dimer
      proteins. The PGRP dimers maintain their biological functions. We detected the
      PGRP-S dimer in human serum and polymorphonuclear cells, from where it is
      secreted after degranulation; these cells being a possible source of serum PGRP
      S. Recombinant PGRP do not act as bactericidal or bacteriostatic agents in the
      assayed conditions; however, PGRP-S and PGRP-Ialpha cause slight damage in the
      bacterial membrane. Monocytes/macrophages increase Staphylococcus aureus
      phagocytosis in the presence of PGRP-S, PGRP-Ialpha and PGRP-Ibeta. All PGRP bind
      to monocyte/macrophage membranes and are endocytosed by them. In addition, all
      PGRP protect cells from PGN-induced apoptosis. PGRP increase THP-1 cell
      proliferation and enhance activation by PGN. PGRP-S-PGN complexes increase the
      membrane expression of CD14, CD80 and CD86, and enhance secretion of interleukin
      8, interleukin-12 and tumour necrosis factor-alpha, but reduce interleukin-10,
      clearly inducing an inflammatory profile. 

PMID- 25752770
TI  - Prediction of O-glycosylation sites based on multi-scale composition of amino
      acids and feature selection.
AB  - Protein glycosylation is one of the most important and complex post-translational
      modification that provides greater proteomic diversity than any other post
      translational modification. Fast and reliable computational methods to identify
      glycosylation sites are in great demand. Two key issues, feature encoding and
      feature selection, can critically affect the accuracy of a computational method.
      We present a new O-glycosylation sites prediction method using only amino acid
      sequence information. The method includes the following components: (1) on the
      basis of multi-scale theory, features based on multi-scale composition of amino
      acids were extracted from the training sequences with identified glycosylation
      sites; (2) perform a two-stage feature selection to remove features that had
      adverse effects on the prediction, including a stage one preliminary filtering
      with Student's t test, and a second stage screening through iterative elimination
      using novel pairwise comparisons conducted in random subspace using support
      vector machine. Important features retained are used to build prediction model.
      The method is evaluated with sequence-based tenfold cross-validation tests on
      balanced datasets. The results of our experiments show that our method
      significantly outperforms those reported in the literature in terms of
      sensitivity, specificity, accuracy, Matthew's correlation coefficient. The
      prediction accuracy of serine and threonine residues sites reached 95.7 and
      92.7%. The Matthew correlation coefficient of our method for S and T sites is
      0.914 and 0.873, respectively. This method can evaluate each feature with the
      interactions of the rest of the features, which are still included in the model
      and have the advantage of high efficiency.

PMID- 25752772
TI  - A new design method for extracorporeal high-intensity focused ultrasound annular
      array.
AB  - Considering the damage to normal tissues during the high-intensity focused
      ultrasound ablation of the tumor is important. The purpose of this work was to
      design the annular array under the considerations of preventing the skin burn and
      damage to normal tissues behind the tumor target. Based on the Rayleigh
      Summerfield pressure integral, the numerical acoustic intensity field of a
      spherical bowl annular array with a diameter of 12 cm and a radius of curvature
      of 12 cm was obtained by using the MATLAB software. An absorbed intensity ratio
      of the normal tissue to target was proposed to define the allowable grating lobe
      for determining the focusing range. The analytic results showed that for the
      treatment of uterine fibroids, the focusing range increased as the number of the
      element increased from 9 to 22 and the 14-ring array at the operating frequency
      of 0.8, 0.9 or 1.0 MHz had a focusing range larger than 5.5 cm when the range was
      only 4 cm at 1.2 MHz. For the treatment of medullary carcinoma and scirrhous
      carcinoma in breast, the focusing range of the 0.9-MHz, 14-ring annular array was
      8-12 and 8-14 cm, respectively. 

PMID- 25752771
TI  - Comparative study of a muscle stiffness sensor and electromyography and
      mechanomyography under fatigue conditions.
AB  - This paper proposes the feasibility of a stiffness measurement for muscle
      contraction force estimation under muscle fatigue conditions. Bioelectric signals
      have been widely studied for the estimation of the contraction force for physical
      human-robot interactions, but the correlation between the biosignal and actual
      motion is decreased under fatigue conditions. Muscle stiffness could be a useful
      contraction force estimator under fatigue conditions because it measures the same
      physical quantity as the muscle contraction that generates the force.
      Electromyography (EMG), mechanomyography (MMG), and a piezoelectric resonance
      based active muscle stiffness sensor were used to analyze the biceps brachii
      under isometric muscle fatigue conditions with reference force sensors at the end
      of the joint. Compared to EMG and MMG, the change in the stiffness signal was
      smaller (p < 0.05) in the invariable contraction force generation test until
      failure. In addition, in the various contraction level force generation tests,
      the stiffness signal under the fatigue condition changed <10% (p < 0.05) compared
      with the signal under non-fatigue conditions. This result indicates that the
      muscle stiffness signal is less sensitive to muscle fatigue than other
      biosignals. This investigation provides insights into methods of monitoring and
      compensating for muscle fatigue.

PMID- 25752773
TI  - In vitro affinity reduction of biologic response modifiers from production buffy
      coat platelets exposed to recombinant protein receptors.
AB  - BACKGROUND: Recent studies link biologic response modifiers found in donor
      platelet (PLT) concentrates to transfusion reactions. We tested a novel method to
      deplete BRMs from PLT concentrates using apheresis. STUDY DESIGN AND METHODS:
      Whole blood from 25 donors was treated to yield PLTs for in vitro measurements on
      Days 2, 5, and 7. On Day 7, PLTs were filtrated through columns with either
      antibody-coated agarose or rh-megalin bound to antibody-coated agarose. In
      addition, we also tested the naked matrix (agarose) and another apheresis surface
      containing rh-cubilin bound to agarose. Megalin and cubilin are parts of the
      protein complex mediating BRM endocytosis in the human kidney. RESULTS: Compared
      to before filtration (951 * 10(9)  +/- 41 * 10(9) cells/L), PLT numbers decreased
      slightly after filtration over both naked (859 * 10(9)  +/- 38 * 10(9) ) and
      antibody-coated (848 * 10(9)  +/- 41 * 10(9) ) matrices (both p < 0.001 vs.
      before). Concentrations of interleukin (IL)-1beta, IL-12 (p40), IL-12 (p70), and
      IL-7 all decreased by approximately 40% even in the absence of a recombinant
      surface. After filtration over rh-cubilin, but not rh-megalin, concentrations of
      IFN-gamma, IL-1beta, tumor necrosis factor-alpha, IL-12, and IL-7 all further
      decreased by 30% to 50%. CONCLUSION: In a pilot study of in vitro apheresis to
      deplete BRMs, we found that cell numbers and function remained largely unaffected
      by filtration. Significant reductions in BRMs occurred already with agarose.
      However, apheresis with the multiligand receptor rh-cubilin was able to further
      decrease concentrations.

PMID- 25752775
TI  - Current state of allocation of oral health human resources in northern China and
      future needs.
AB  - OBJECTIVE: The aim of the present investigation was to describe the distribution,
      structure and allocation of oral health services personnel, evaluate oral health
      service capacity and predict the needs for oral health services in northern China
      over the coming 10 years. METHODS: The questionnaires were sent to all the dental
      medical institutions included in this study directly from the Sanitation Bureau
      and the Health Supervision Station. All the institutions and dental personnel
      were asked to fill out the questionnaires, and then, the questionnaires were
      collected through postal service and email. RESULTS: In Liaoning Province, which
      is in northern China, there are a total of 5617 dentists in total, 87.8% of whom
      are located in urban areas. Dentists in rural areas were found to be less
      educated and specialized. The ratio of dentists to nurses to technicians was
      about 6:2:1, and the ratio of dentists to total population was 1:7682. It was
      predicted that, in 2020, the number of dentists could reach 13 207. This would
      meet the area's needs for oral health services. CONCLUSION: Currently, in
      northern China, the oral health infrastructure suffers from an insufficient
      number of dental professionals, disproportionate distribution and inappropriate
      structure. To improve social equity, it is necessary to adjust the distribution
      of dental personnel capable of performing for oral health services.

PMID- 25752774
TI  - Preventive analgesia and novel strategies for the prevention of chronic post
      surgical pain.
AB  - Chronic post-surgical pain (CPSP) is a serious complication of major surgery that
      can impair a patient's quality of life. The development of CPSP is a complex
      process which involves biologic, psychosocial, and environmental mechanisms that
      have yet to be fully understood. Currently perioperative pharmacologic
      interventions aim to suppress and prevent sensitization with the aim of reducing
      pain and analgesic requirement in acute as well as long-term pain . Despite the
      detrimental effects of CPSP on patients, the body of literature focused on
      treatment strategies to reduce CPSP remains limited and continues to be
      understudied. This article reviews the main pharmacologic candidates for the
      treatment of CPSP, discusses the future of preventive analgesia, and considers
      novel strategies to help treat acute post-operative pain and lessen the risk that
      it becomes chronic. In addition, this article highlights important areas of focus
      for clinical practice including: multimodal management of CPSP patients,
      psychological modifiers of the pain experience, and the development of a
      Transitional Pain Service specifically designed to manage patients at high risk
      of developing chronic post-surgical pain. 

PMID- 25752776
TI  - Ocular Motor Score (OMS): a clinical tool to evaluating ocular motor functions in
      children. Intrarater and inter-rater agreement.
AB  - PURPOSE: Ocular motor score (OMS) is a new clinical test protocol for evaluating
      ocular motor functions in children and young adults. OMS is a set of 15 important
      and relevant non-invasive ocular motor function parameters derived from clinical
      practice. The aim of the study was to evaluate OMS according to intrarater and
      inter-rater agreement. METHODS: Forty children aged 4-10 years, 23 girls median
      age 6.5 (range 4.3-9.3) and 17 boys median age 5.8 (range 4.1-9.8) were included.
      The ocular motor functions were assessed and scored according to the OMS
      protocol. The examinations were videotaped. To obtain the intrarater agreement,
      the first author examined and scored the children twice, first in the clinic and
      2 weeks later by watching the videotape. To obtain the inter-rater agreement,
      three other raters independently scored the ocular motor function of the children
      by watching the videotapes. RESULTS: The overall observed intrarater agreement
      was 88%, and the observed inter-rater agreement between the three raters was 80%.
      For none of the subtests was there an observed intrarater agreement lower than
      65%. Three of the subtests had an observed inter-rater agreement of 65% or below.
      CONCLUSION: Overall there was high observed intra- and inter-rater agreement for
      the OMS test protocol. Subtests such as saccades and smooth pursuit were more
      difficult for raters to score similarly according the clinical OMS test protocol.

PMID- 25752777
TI  - Prophylactic antibiotics in dermatological surgery.
AB  - This is a review of the common pathogens of surgical site infections, antibiotic
      coverage for particular anatomical sites, mechanisms by which surgical site
      infections occur and the latest data and recommendations for prophylactic
      antibiotics in the prevention of surgical site infections, infective endocarditis
      and haematogenous joint infections. Recent evidence-based guidelines on surgical
      prophylaxis is for restricted indications and a shorter duration of antibiotic
      prophylaxis in situations where no clinical benefit of prolonged therapy has been
      proven, in order to minimise the potential adverse ecological and clinical
      effects associated with antibiotic therapy. This review recommends the cautious
      use of prophylactic antibiotics in dermatological surgery to help prevent the
      growing problem of bacterial resistance as well as other morbidity and health
      care costs. 

PMID- 25752778
TI  - Heterogeneity of physical function responses to exercise training in older
      adults.
AB  - OBJECTIVES: To describe the interindividual variability in physical function
      responses to supervised resistance and aerobic exercise training interventions in
      older adults. DESIGN: Data analysis of two randomized, controlled exercise
      trials. SETTING: Community-based research centers. PARTICIPANTS: Overweight and
      obese (body mass index (BMI)>=27.0 kg/m2) sedentary men and women aged 65 to 79
      (N=95). INTERVENTION: Five months of 4 d/wk of aerobic training (AT, n=40) or 3
      d/wk of resistance training (RT, n=55). MEASUREMENTS: Physical function
      assessments: global measure of lower extremity function (Short Physical
      Performance Battery (SPPB)), 400-m walk, peak aerobic capacity (VO2 peak), and
      knee extensor strength. RESULTS: On average, both exercise interventions
      significantly improved physical function. For AT, there was a 7.9% increase in
      VO2 peak; individual absolute increases varied from 0.4 to 4.3 mL/kg per minute,
      and four participants (13%) showed no change or a decrease in VO2 peak. For RT,
      knee extensor strength improved an average of 8.1%; individual increases varied
      from 1.2 to 63.7 Nm, and 16 participants (30%) showed no change or a decrease in
      strength. Usual gait speed, 400-m walk time, chair rise time, and SPPB improved
      for the majority of AT participants and usual gait speed, chair rise time, and
      SPPB improved for the majority of RT participants, but there was wide variation
      in the magnitude of improvement. Only change in 400-m walk time with RT was
      related to exercise adherence (correlation coefficient=-0.31, P=.004).
      CONCLUSION: Despite sufficient levels of adherence to both exercise
      interventions, some participants did not improve function, and the magnitude of
      improvement varied widely. Additional research is needed to identify factors that
      optimize responsiveness to exercise to maximize its functional benefits in older
      adults.

PMID- 25752779
TI  - How useful are national caesarean section rates for monitoring quality of
      perinatal care?

PMID- 25752780
TI  - The sinus venosus myocardium contributes to the atrioventricular canal: potential
      role during atrioventricular node development?
AB  - The presence of distinct electrophysiological pathways within the
      atrioventricular node (AVN) is a prerequisite for atrioventricular nodal
      reentrant tachycardia to occur. In this study, the different cell contributions
      that may account for the anatomical and functional heterogeneity of the AVN were
      investigated. To study the temporal development of the AVN, the expression
      pattern of ISL1, expressed in cardiac progenitor cells, was studied in sequential
      stages performing co-staining with myocardial markers (TNNI2 and NKX2-5) and HCN4
      (cardiac conduction system marker). An ISL1+/TNNI2+/HCN4+ continuity between the
      myocardium of the sinus venosus and atrioventricular canal was identified in the
      region of the putative AVN, which showed a pacemaker-like phenotype based on
      single cell patch-clamp experiments. Furthermore, qPCR analysis showed that even
      during early development, different cell populations can be identified in the
      region of the putative AVN. Fate mapping was performed by in ovo vital dye
      microinjection. Embryos were harvested and analysed 24 and 48 hrs post-injection.
      These experiments showed incorporation of sinus venosus myocardium in the
      posterior region of the atrioventricular canal. The myocardium of the sinus
      venosus contributes to the atrioventricular canal. It is postulated that the
      myocardium of the sinus venosus contributes to nodal extensions or transitional
      cells of the AVN since these cells are located in the posterior region of the
      AVN. This finding may help to understand the origin of atrioventricular nodal
      reentrant tachycardia. 

PMID- 25752781
TI  - Expression and cellular localization of the transcription factor NeuroD1 in the
      developing and adult rat pineal gland.
AB  - Circadian rhythms govern many aspects of mammalian physiology. The daily pattern
      of melatonin synthesis and secretion is one of the classic examples of circadian
      oscillations. It is mediated by a class of neuroendocrine cells known as
      pinealocytes which are not yet fully defined. An established method to evaluate
      functional and cytological characters is through the expression of lineage
      specific transcriptional regulators. NeuroD1 is a basic helix-loop-helix
      transcription factor involved in the specification and maintenance of both
      endocrine and neuronal phenotypes. We have previously described developmental and
      adult regulation of NeuroD1 mRNA in the rodent pineal gland. However, the
      transcript levels were not influenced by the elimination of sympathetic input,
      suggesting that any rhythmicity of NeuroD1 might be found downstream of
      transcription. Here, we describe NeuroD1 protein expression and cellular
      localization in the rat pineal gland during development and the daily cycle. In
      embryonic and perinatal stages, protein expression follows the mRNA pattern and
      is predominantly nuclear. Thereafter, NeuroD1 is mostly found in pinealocyte
      nuclei in the early part of the night and in cytoplasm during the day, a rhythm
      maintained into adulthood. Additionally, nocturnal nuclear NeuroD1 levels are
      reduced after sympathetic disruption, an effect mimicked by the in vivo
      administration of alpha- and beta-adrenoceptor blockers. NeuroD1 phosphorylation
      at two sites, Ser(274) and Ser(336) , associates with nuclear localization in
      pinealocytes. These data suggest that NeuroD1 influences pineal phenotype both
      during development and adulthood, in an autonomic and phosphorylation-dependent
      manner. 

PMID- 25752782
TI  - A case of allergic contact dermatitis caused by arbutin.

PMID- 25752785
TI  - Rare events can be fatal and must not be ignored; how much needs to happen before
      we act?

PMID- 25752786
TI  - Cuffed or uncuffed endotracheal tubes in pediatric anesthesia: a survey of
      current practice in the United Kingdom and The Netherlands.

PMID- 25752787
TI  - Risks of fixed-angle supraglottic airways in infants.

PMID- 25752788
TI  - Quick and safe intubation by visualized passage of the tube-armed Bonfils
      fiberscope into the trachea.

PMID- 25752789
TI  - Effects of anesthesia and surgery on the developing brain: problem solved?

PMID- 25752790
TI  - Effects of anesthesia on the developing brain: can the underlying disease be
      ignored?

PMID- 25752791
TI  - It's not about the endotracheal tube: reply to editorial on our paper
      "Endotracheal intubation in the pediatric emergency department".

PMID- 25752792
TI  - Pediatric endobronchial blockers in infants: a refinement in technique.

PMID- 25752793
TI  - Antioxidant and toxicological evaluation of a Tamarindus indica L. leaf fluid
      extract.
AB  - In the scientific community, there is a growing interest in Tamarindus indica L.
      leaves, both as a valuable nutrient and as a functional food. This paper focuses
      on exploring its safety and antioxidant properties. A tamarind leaf fluid extract
      (TFE) wholly characterised was evaluated for its anti-DPPH activity (IC50 = 44.36
      MUg/mL) and its reducing power activity (IC50 = 60.87 MUg/mL). TFE also exhibited
      a high ferrous ion-chelating capacity, with an estimated binding constant of
      1.085 mol L(-1) while its influence over nitric oxide production in human
      leucocytes was irregular. At low concentrations, TFE stimulated NO output, but it
      significantly inhibited it when there was an increase in concentration. TFE was
      also classified as a non-toxic substance in two toxicity tests: the acute oral
      toxicity test and the oral mucous irritability test. Further toxicological assays
      are needed, although results so far suggest that TFE might become a functional
      dietary supplement.

PMID- 25752794
TI  - Engineering of pyranose dehydrogenase for application to enzymatic anodes in
      biofuel cells.
AB  - In the search for improved glucose oxidising enzymes for biofuel cells, a number
      of Agaricus meleagris (Am) pyranose dehydrogenase mutants (mPDHs) exhibiting
      different degrees of glycosylation were produced using site-directed mutagenesis
      and electrochemically characterised. The response of electrodes modified with
      different mPDHs is compared in a mediated electron transfer mode, where the
      electrodes are modified with each of the mutants covalently attached to redox
      polymers based on polyvinylimidazole-bound osmium complexes using a cross-linking
      agent. Coating of each of the enzymes onto the graphite electrode surface is also
      used to screen for their capacity for direct electron transfer. The double mutant
      PDH exhibits the highest response to glucose at physiological pH in both direct
      and mediated electron transfer modes, producing a Jmax of ~800 MUA cm(-2) at room
      temperature and when "wired" to the Os-polymer having the highest formal
      potential. From the results obtained the double mPDH is proposed as the most
      suitable candidate for application to bioanode fabrication. 

PMID- 25752795
TI  - Subsequent risk of metabolic syndrome in women with a history of preeclampsia:
      data from the Health Examinees Study.
AB  - BACKGROUND: To investigate whether preeclampsia is independently associated with
      risk of future metabolic syndrome and whether any such primary associations are
      modified by different ages at first pregnancy. METHODS: Based on the Health
      Examinees Study, a cross-sectional analysis was conducted. Data of women (n = 49
      780) who had experienced at least 1 pregnancy during their lifetime and had never
      been diagnosed with any metabolic disorder before their pregnancy were analyzed
      using multiple logistic regression models. Odds ratios (ORs) and 95% confidence
      intervals (CIs) were estimated after adjusting for age, lifestyle
      characteristics, and reproductive factors. A stratified analysis was also
      conducted to estimate the extent of the primary association between preeclampsia
      and future metabolic syndrome by age at first pregnancy. RESULTS: Women with a
      history of preeclampsia had significantly increased odds of developing metabolic
      syndrome (adjusted OR 1.23; 95% CI, 1.12-1.35), central obesity (adjusted OR
      1.36; 95% CI, 1.25-1.47), elevated blood pressure (adjusted OR 1.53; 95% CI, 1.41
      1.67), or elevated fasting glucose (adjusted OR 1.13; 95% CI, 1.03-1.25) in later
      life. In the stratified analysis, women who first became pregnant at ages >35
      years and had preeclampsia were found to be at significantly increased likelihood
      of metabolic syndrome later in life (adjusted OR 4.38; 95% CI, 1.62-11.9).
      CONCLUSIONS: Our findings suggest that preeclampsia increases the risk of
      metabolic syndrome in later life, and late age at first pregnancy can further
      exacerbate this risk.

PMID- 25752796
TI  - Utilization of human nuclear receptors as an early counter screen for off-target
      activity: a case study with a compendium of 615 known drugs.
AB  - Off-target effects of drugs on nuclear hormone receptors (NHRs) may result in
      adverse effects in multiple organs/physiological processes. Reliable assessments
      of the NHR activities for drug candidates are therefore crucial for drug
      development. However, the highly permissive structures of NHRs for vastly
      different ligands make it challenging to predict interactions by examining the
      chemical structures of the ligands. Here, we report a detailed investigation on
      the agonistic and antagonistic activities of 615 known drugs or drug candidates
      against a panel of 6 NHRs: androgen, progesterone, estrogen alpha/beta, and
      thyroid hormone alpha/beta receptors. Our study revealed that 4.7 and 12.4%
      compounds have agonistic and antagonistic activities, respectively, against this
      panel of NHRs. Nonetheless, potent, unintended NHR hits are relatively rare among
      the known drugs, indicating that such interactions are perhaps not tolerated
      during drug development. However, we uncovered examples of compounds that
      unintentionally agonize or antagonize NHRs. In addition, a number of compounds
      showed multi-NHR activities, suggesting that the cross-talk between multiple NHRs
      co-operate to elicit in vivo effects. These data highlight the merits of counter
      screening drug candidate against NHRs during drug discovery/development.

PMID- 25752797
TI  - Characterization of arsenic hepatobiliary transport using sandwich-cultured human
      hepatocytes.
AB  - Arsenic is a proven human carcinogen and is associated with a myriad of other
      adverse health effects. This metalloid is methylated in human liver to
      monomethylarsonic acid (MMA(V)), monomethylarsonous acid (MMA(III)),
      dimethylarsinic acid (DMA(V)), and dimethylarsinous acid (DMA(III)) and
      eliminated predominantly in urine. Hepatic basolateral transport of arsenic
      species is ultimately critical for urinary elimination; however, these pathways
      are not fully elucidated in humans. A potentially important human hepatic
      basolateral transporter is the ATP-binding cassette (ABC) transporter multidrug
      resistance protein 4 (MRP4/ABCC4) that in vitro is a high-affinity transporter of
      DMA(V) and the diglutathione conjugate of MMA(III) [MMA(GS)(2)]. In rats, the
      related canalicular transporter Mrp2/Abcc2 is required for biliary excretion of
      arsenic as As(GS)(3) and MMA(GS)(2). The current study used sandwich cultured
      human hepatocytes (SCHH) as a physiological model of human arsenic hepatobiliary
      transport. Arsenic efflux was detected only across the basolateral membrane for 9
      out of 14 SCHH preparations, 5 had both basolateral and canalicular efflux.
      Basolateral transport of arsenic was temperature- and GSH-dependent and inhibited
      by the MRP inhibitor MK-571. Canalicular efflux was completely lost after GSH
      depletion suggesting MRP2-dependence. Treatment of SCHH with As(III) (0.1-1 uM)
      dose-dependently increased MRP2 and MRP4 levels, but not MRP1, MRP6, or
      aquaglyceroporin 9. Treatment of SCHH with oltipraz (Nrf2 activator) increased
      MRP4 levels and basolateral efflux of arsenic. In contrast, oltipraz increased
      MRP2 levels without increasing biliary excretion. These results suggest arsenic
      basolateral transport prevails over biliary excretion and is mediated at least in
      part by MRPs, most likely including MRP4.

PMID- 25752798
TI  - Residents' self-reported quality of life in long-term care facilities in Canada.
AB  - Quality of life (QoL) of long-term care (LTC) facility residents is an important
      outcome of care. This cross-sectional, descriptive study examined the self
      reported QoL of LTC facility residents in Canada using the interRAI Self-Report
      Nursing Home Quality of Life Survey instrument. A secondary purpose was to test
      the instrument's psychometric properties. Psychometric testing of the instrument
      supported its reliability and its convergent and content validity for assessing
      the residents' QoL. Findings showed that residents rated positively several
      aspects of their life, such as having privacy during visits (76.9%) and staff's
      being honest with them (73.6%). Residents gave lower ratings to other aspects
      such as autonomy, staff-resident bonding, and personal relationships. The
      findings point to gaps between facility philosophies of care and their
      translation into a care environment where care is truly resident-directed.
      Moreover, the findings have potential implications for resident care planning,
      facility programming, social policy development, and future research. 

PMID- 25752800
TI  - Sulfoxide-Directed Metal-Free ortho-Propargylation of Aromatics and
      Heteroaromatics.
AB  - A sulfoxide-directed, metal-free ortho-propargylation of aromatics and
      heteroaromatics exploits intermolecular delivery of a propargyl nucleophile to
      sulfur followed by an intramolecular relay to carbon. The operationally simple
      cross-coupling procedure is general, regiospecific with regard to the propargyl
      nucleophile, and shows complete selectivity for products of ortho-propargylation
      over allenylation. The use of secondary propargyl silanes allows metal-free ortho
      coupling to form carbon-carbon bonds between aromatic and heteroaromatic rings
      and secondary propargylic centres. The 'safety-catch' nature of the sulfoxide
      directing group is illustrated in a selective, iterative double cross-coupling
      process. The products of propargylation are versatile intermediates and they have
      been readily converted into substituted benzothiophenes. 

PMID- 25752799
TI  - How do disordered regions achieve comparable functions to structured domains?
AB  - The traditional structure to function paradigm conceives of a protein's function
      as emerging from its structure. In recent years, it has been established that
      unstructured, intrinsically disordered regions (IDRs) in proteins are equally
      crucial elements for protein function, regulation and homeostasis. In this
      review, we provide a brief overview of how IDRs can perform similar functions to
      structured proteins, focusing especially on the formation of protein complexes
      and assemblies and the mediation of regulated conformational changes. In addition
      to highlighting instances of such functional equivalence, we explain how
      differences in the biological and physicochemical properties of IDRs allow them
      to expand the functional and regulatory repertoire of proteins. We also discuss
      studies that provide insights into how mutations within functional regions of
      IDRs can lead to human diseases.

PMID- 25752801
TI  - Progressive osseous heteroplasia in a 7-year-old girl with osteoma cutis and
      autoimmune thyroiditis: the importance of investigating GNAS mutations.

PMID- 25752802
TI  - Evaluation of application possibility of water containing organic acids for
      chemical denture cleaning for older adults.
AB  - AIM: The purpose of the present study was to evaluate the application possibility
      of water containing organic acids (WOA), made by some organic acids used as food
      additives, for chemical denture cleaning for older adults by microbial
      investigation. METHODS: Using an in vitro biofilm study, we determined the
      effects of WOA on Streptococcus sanguinis, S. pneumoniae and Candida albicans
      attached to heat-cured acrylic resins. Specimens were divided into three groups
      as follows: control group (TW), commercial denture cleaner group (DC) and WOA
      group (WOA). Specimens were treated with each for 5 min, 30 min or 8 h, and the
      numbers of attached microbes were determined by counting colony-forming units or
      adenosine triphosphate analysis. Using an in vivo biofilm study, we studied the
      effects of these same solutions on 60 complete dentures. The dentures were
      divided randomly and blindness into three groups as described above, and treated
      for 10 min. The numbers of microbes attached to dentures before and after
      treatment were determined by counting colony-forming units. RESULTS: For the in
      vitro biofilm study, there were significant differences in the numbers of
      microbes between WOA and TW, although there were no significant differences
      between WOA and DC except for C. albicans. For the in vivo biofilm study, there
      were significant differences between WOA, DC and TW, although there was no
      significant difference between WOA and DC. CONCLUSION: We conclude that water
      containing organic acids exerts antimicrobial effects as strong as commercial
      denture cleaner, and it has an application possibility of use for safe chemical
      denture cleaning for older adults.

PMID- 25752803
TI  - Diversity of extremely halophilic cultivable prokaryotes in Mediterranean,
      Atlantic and Pacific solar salterns: Evidence that unexplored sites constitute
      sources of cultivable novelty.
AB  - The culturable fraction of aerobic, heterotrophic and extremely halophilic
      microbiota retrieved from sediment and brine samples of eight sampling sites in
      the Mediterranean, Canary Islands and Chile was studied by means of a tandem
      approach combining large-scale cultivation, MALDI-TOF MS targeting whole cell
      biomass, and phylogenetic reconstruction based on 16S rRNA gene analysis. The
      approach allowed the identification of more than 4200 strains and a comparison
      between different sampling sites. The results indicated that the method
      constituted an excellent tool for the discovery of taxonomic novelty. Four new
      genera and nine new species could be identified within the archaeal family
      Halobacteriaceae, as well as one new bacterial species, and a representative of
      Salinibacter ruber phylotype II, a group that had been refractory to isolation
      for the last fifteen years. Altogether, the results indicated that in order to
      provide better yields for the retrieval of novel taxa from the environment,
      performance of non-redundant environment sampling is recommended together with
      the screening of large sets of strains. 

PMID- 25752804
TI  - Boundary condition effects on the dynamic and electric properties of hydration
      layers.
AB  - Water solvation has a central role in several biochemical processes ranging from
      protein folding to biomolecular recognition and enzyme catalysis. Because of its
      importance, the structure and dynamics of hydration layers around biological
      macromolecules have been the targets of a great number of experimental and
      computational studies. In the present contribution, we have investigated the
      effects of periodic boundary conditions (PBCs), as used in conjunction with
      molecular dynamics (MD) simulations, on the dynamic and electric properties of
      water layers. In particular, we have systematically performed MD simulations of
      neat water and biomolecules in aqueous solutions by imposing a different external
      dielectric constant, a generally overlooked parameter in PBC simulations. The
      effect of the system size has also been addressed. Overall, our results
      consistently indicate that the dipole moment properties of water layers, and
      specifically the dipole moment fluctuations and the reorientational correlation
      functions, can be sensitive to the choice of the external boundary conditions,
      whereas other molecular properties, such as the self-diffusion coefficient and
      the reorientational relaxation times, are not affected. We think that our
      investigation may help to assess appropriate simulation conditions for modeling
      the aqueous environment of relevant biochemical systems and processes. 

PMID- 25752805
TI  - Enhancing k-space quantitative susceptibility mapping by enforcing consistency on
      the cone data (CCD) with structural priors.
AB  - PURPOSE: The inversion from the magnetic field to the magnetic susceptibility
      distribution is ill-posed because the dipole kernel, which relates the magnetic
      susceptibility to the magnetic field, has zeroes at a pair of cone surfaces in
      the k-space, leading to streaking artifacts on the reconstructed quantitative
      susceptibility maps (QSM). A method to impose consistency on the cone data (CCD)
      with structural priors is proposed to improve the solutions of k-space methods.
      METHODS: The information in the cone region is recovered by enforcing structural
      consistency with structural prior, while information in the noncone trust region
      is enforced to be consistent with the magnetic field measurements in k-space.
      This CCD method was evaluated by comparing the initial results of existing QSM
      algorithms to the QSM results after CCD enhancement with respect to the COSMOS
      results in simulation, phantom, and in vivo human brain. RESULTS: The proposed
      method demonstrated suppression of streaking artifacts and the resulting QSM
      showed better agreement with reference standard QSM compared with other k-space
      based methods. CONCLUSION: By enforcing consistency with structural priors in the
      cone region, the missing data in the cone can be recovered and the streaking
      artifacts in QSM can be suppressed.

PMID- 25752806
TI  - Management of pediatric intestinal failure.
AB  - Intestinal failure (IF) is defined as the state of the intestinal tract where the
      function is below the minimum required for the absorption of macronutrients,
      water, and electrolytes. The etiology may be a multitude of causes, but short
      bowel syndrome (SBS) remains the most common. The successful management and
      prognosis of SBS in infants and children depends a multitude of variables such as
      length, quality, location, and anatomy of the remaining intestine. Prognosis,
      likewise, depends on these factors, but also is dependent on the clinical
      management of these patients. Strategies for a successful outcome and the success
      of therapeutic interventions are dependent upon understanding each individual's
      remaining intestinal function. Medical intervention success is defined by a
      graduated advancement of enteral nutrition (EN) and a reduction of parenteral
      nutrition (PN). Complications of IF and PN include progressive liver disease,
      bacterial overgrowth, dysmotility, renal disease, catheter related bloodstream
      infections, and loss of venous access. Surgical interventions such as bowel
      lengthening procedures show promise in carefully selected patients. Intestinal
      transplantation is reserved for those infants and children suffering from life
      threatening complications of PN. 

PMID- 25752808
TI  - Integrating bio-inorganic and analytical chemistry into an undergraduate
      biochemistry laboratory.
AB  - Undergraduate laboratories expose students to a wide variety of topics and
      techniques in a limited amount of time. This can be a challenge and lead to less
      exposure to concepts and activities in bio-inorganic chemistry and analytical
      chemistry that are closely-related to biochemistry. To address this, we
      incorporated a new iron determination by atomic absorption spectroscopy exercise
      as part of a five-week long laboratory-based project on the purification of
      myoglobin from beef. Students were required to prepare samples for chemical
      analysis, operate an atomic absorption spectrophotometer, critically evaluate
      their iron data, and integrate these data into a study of myoglobin.

PMID- 25752809
TI  - Non-clinical safety assessment of single and repeated intramuscular
      administration of a human papillomavirus-16/18 vaccine in rabbits and rats.
AB  - The human papillomavirus (HPV)-16/18 vaccine (Cervarix(r)) is a prophylactic
      vaccine for the prevention of cervical cancer. The vaccine contains recombinant
      virus-like particles assembled from the L1 major capsid proteins of the cervical
      cancer-causing viral types HPV-16 and HPV-18, and Adjuvant System 04 (AS04),
      which contains the immunostimulant MPL and aluminium salt. To evaluate potential
      local and systemic toxic effects of the HPV-16/18 vaccine or AS04 alone, three
      repeated-dose studies were performed in rabbits and rats. One rabbit study also
      included a single-dose evaluation. In rabbits (~2.5 kg), the full human dose (HD)
      of the vaccine was evaluated (0.5 ml per injection site), and in rats (~250 g),
      1/5 HD of vaccine was evaluated, corresponding to >= 12 times the dosage in
      humans relative to body weight. In both animal models, the treatment-related
      changes included a slight transient increase in the number of circulating
      neutrophils as well as a local inflammatory reaction at the injection site. These
      treatment-related changes were less pronounced after four doses of AS04 alone
      than after four doses of the HPV-16/18 vaccine. Additional treatment-related
      changes in the rat included lower albumin/globulin ratios and microscopic signs
      of inflammation in the popliteal lymph nodes. In both animal models, 13 weeks
      after the fourth dose, recovery was nearly complete, although at the injection
      site in some animals there were signs of discoloration, muscle-fibre regeneration
      and focal points of macrophage infiltration. Therefore, in these non-clinical
      models, the single and repeated dose administrations of the HPV-16/18 vaccine or
      AS04 alone were safe and well tolerated.

PMID- 25752810
TI  - The use of ATG abrogates the antileukemic effect of cytomegalovirus reactivation
      in patients with acute myeloid leukemia receiving grafts from unrelated donors.
AB  - Several studies provided evidence of a consistent antileukemic effect induced by
      cytomegalovirus (CMV) replication in acute myeloid leukemia (AML) patients
      receiving allogeneic hematopoietic stem cell transplantation (HSCT), however the
      use of antithymocyte globulin (ATG) as graft-versus-host disease prophylaxis, may
      potentially abrogate the protective effect of CMV infection. To address this
      issue, we retrospectively analyzed the risk of relapse in a cohort of 101
      patients with AML who received grafts from an unrelated donor after a
      conditioning regimen including ATG. The cumulative incidence of CMV reactivation,
      evaluated by RT qPCR, was 59% at 12 months, and 93% of CMV reactivations occurred
      within the first 100 days post HSCT. The 5-year cumulative incidence of relapse
      in patients with CMV reactivation was 29% compared with 37% for patients without
      CMV reactivation, and the only factor associated with a reduced 5-year cumulative
      incidence of relapse was the disease status at HSCT (P < 0.001). In the
      multivariable model adverse cytogenetics (HR 2.42, 95% CI 1.02-5.72; P = 0.044)
      and acute GVHD (HR 3.36, 95% CI 1.32-8.54; P =  0.011) were independent risk
      factors for reducing overall survival (OS), while the presence of chronic GVHD
      was associated with a better OS (HR 0.37, 95% CI 0.15-0.89; P = 0.027). CMV
      replication was not an independent risk factor for OS (HR 1.06, 95% CI 0.07
      15.75; P = 0.965). In Conclusion, the results of present study suggest that
      relapse prevention in patients with AML receiving T-cell depleted HSCT using ATG
      do not benefit from CMV reactivation.

PMID- 25752811
TI  - The use of fabricated chimeric flap for reconstruction of extensive foot defects.
AB  - Repair of extensive foot defects requires both adequate tissues for wound
      coverage and special tissues for functional reconstruction. To maximize its
      function reconstruction, fabricated chimeric flaps consisting of multiple
      separate flaps were designed to reconstruct such defects. Five patients suffered
      extensive foot defects with sizes ranging from 23 * 12 cm to 38 * 14 cm(2) in
      multiple regions including heel, forefoot, dorsum, ankle, anterior leg, and even
      toes. Causes included crushing injuries, avulsion injuries, and scar excision.
      Most areas of the defects except heel were first covered by latissimus dorsi
      muscle flap or anterolateral thigh flap and their pedicles were anastomosed with
      recipient vessels. Then free medial plantar flaps were transferred for heel
      reconstruction and their pedicles were further attached to either side branches
      of the main source vessel or to its distal continuation. All chimeric flaps
      survived uneventfully and all patients were able to walk in normal footwear
      during the 1.5- to 4-years follow-up. None of the flaps developed ulcer and flap
      breakdown. The assessment by Maryland Foot Score showed that four of the five
      patients gained a "good" recovery and one patient showed moderate improvement of
      foot functions. Appearances of reconstructed heels were near-normal. The results
      indicate that fabricated chimeric flap has good design flexibility and may
      provide an option for functional reconstruction of extensive foot defects. (c)
      2015 Wiley Periodicals, Inc. Microsurgery 36:303-309, 2016. 

PMID- 25752807
TI  - Adverse effects reported in the use of gastroesophageal reflux disease treatments
      in children: a 10 years literature review.
AB  - Gastroesophageal reflux (GER) is commonly observed in children, particularly
      during the first year of life. Pharmacological therapy is mostly reserved for
      symptomatic infants diagnosed with GER disease (GERD), usually as defined in a
      recent consensus statement. The purpose of the present article was to review the
      reported adverse effects of pharmacological agents used in the treatment of
      paediatric GERD. We conducted this review using the electronic journal database
      Pubmed and Cochrane database systematic reviews using the latest 10-year period
      (1 January 2003 to 31 December 2012). Our search strategy included the following
      keywords: omeprazole, esomeprazole, lansoprazole, pantoprazole, rabeprazole,
      rantidine, cimetidine, famotidine, nizatidine, domperidone, metoclopramide,
      betanechol, erythromycin, baclofen, alginate. We used Pubmed's own filter of:
      'child: birth-18 years'. All full articles were reviewed and we only included
      randomized controlled trials retrieved from our search. We addressed a summary of
      our search on a drug-by-drug basis with regard to its mechanism of action and
      clinical applications, and reviewed all of the adverse effects reported and the
      safety profile of each drug. Adverse effects have been reported in at least 23%
      of patients treated with histamine H2 receptor antagonists (H2 RAs) and 34% of
      those treated with proton pump inhibitors (PPIs), and mostly include headaches,
      diarrhoea, nausea (H2 RAs and PPIs) and constipation (PPIs). Acid suppression may
      place immune-deficient infants and children, or those with indwelling catheters,
      at risk for the development of lower respiratory tract infections and nosocomial
      sepsis. Prokinetic agents have many adverse effects, without major benefits to
      support their routine use. 

PMID- 25752812
TI  - Selective pressures in the human bony pelvis: Decoupling sexual dimorphism in the
      anterior and posterior spaces.
AB  - OBJECTIVES: Sexual dimorphism in the human bony pelvis is commonly assumed to be
      related to the intensity of obstetrical selective pressures. With intense
      obstetrical selective pressures, there should be greater shape dimorphism; with
      minimal obstetrical selective pressures, there should be reduced shape
      dimorphism. This pattern is seen in the nondimorphic anterior spaces and highly
      dimorphic posterior spaces. Decoupling sexual dimorphism in these spaces may in
      turn be related to the differential influence of other selective pressures, such
      as biomechanical ones. MATERIALS AND METHODS: The relationship between sexual
      dimorphism and selective pressures in the human pelvis was examined using five
      skeletal samples (total female n = 101; male n = 103). Pelvic shape was
      quantified by collecting landmark coordinate data on articulated pelves.
      Euclidean distance matrix analysis was used to extract the distances that defined
      the anterior and posterior pelvic spaces. Sex and body mass were used as proxies
      for obstetrical and biomechanical selective pressures, respectively. RESULTS:
      MANCOVA analyses demonstrate significant effects of sex and body mass on
      distances in both the anterior and the posterior spaces. A comparison of the
      relative contribution of shape variance attributed to each of these factors
      suggests that the posterior space is more influenced by sex, and obstetrics by
      proxy, whereas the anterior space is more influenced by body mass, and
      biomechanics by proxy. CONCLUSIONS: Although the overall shape of the pelvis has
      been influenced by obstetrical and biomechanical selective pressures, there is a
      differential response within the pelvis to these factors. These results provide
      new insight into the ongoing debate on the obstetrical dilemma hypothesis.

PMID- 25752813
TI  - Still lots to learn about human papillomaviruses.

PMID- 25752815
TI  - Signaling pathways in HPV-associated cancers and therapeutic implications.
AB  - Human papillomaviruses (HPVs) are small double-stranded circular DNA viruses with
      8 kb genomes. So far, more than 150 HPVs have been identified, and 12 types of
      HPVs have been conclusively linked to cancer by the International Agency for
      Research on Cancer/World Health Organization. Expression of HPV E5, E6 and E7
      oncoproteins can alter multiple signaling pathways to cause cancer. In this
      review, the signaling pathways activated by these oncoproteins are summarized,
      and targeted therapy against key signaling molecules is described. E6 can
      inactivate tumor protein 53 and PDZ (post synaptic density protein-drosophila
      disk large tumor suppressor-zonula occludens-1 proteins) while stimulating
      phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt), Wnt and Notch pathways.
      E7 can inhibit retinoblastoma protein and stimulate the PI3K/Akt pathway. Both E6
      and E7 can deregulate cellular microRNA expression, which can alter cellular
      signaling pathways. E5 can sensitize epidermal growth factor receptor to
      epidermal growth factor to increase activation of PI3K/Akt and mitogen-activated
      protein kinase pathways. E5 can also inhibit the extrinsic apoptotic pathway.
      These altered signaling pathways could be critical for the initiation and
      maintenance of HPV-associated cancers. Therefore, targeted therapy against the
      key signaling molecules has therapeutic implications. Among these, the
      possibilities of targeting PI3K/Akt, mammalian target of rapamycin, epidermal
      growth factor receptor and vascular endothelial growth factor have been
      extensively studied in many cancers. Some inhibitors have been studied in
      cervical cancer in both animal models and clinical trials. Although the results
      are promising, further investigation is warranted.

PMID- 25752816
TI  - Recent progress in vaccination against human papillomavirus-mediated cervical
      cancer.
AB  - It has been more than 7 years since the commercial introduction of highly
      successful vaccines protecting against high-risk human papillomavirus (HPV)
      subtypes and the development of cervical cancer. From an immune standpoint, the
      dependence of cervical cancer on viral infection has meant that HPV proteins can
      be targeted as strong tumour antigens leading to clearance of the infection and
      the subsequent protection from cancer. Commercially available vaccines consisting
      of the L1 capsid protein assembled as virus-like particles (VLPs) induce
      neutralising antibodies that deny access of the virus to cervical epithelial
      cells. While greater than 90% efficacy has been demonstrated at the completion of
      large phase III trials in young women, vaccine developers are now addressing
      broader issues such as efficacy in boys, longevity of the protection and inducing
      cross-reactive antibody for oncogenic, non-vaccine HPV strains. For women with
      existing HPV infection, the prophylactic vaccines provide little protection, and
      consequently, the need for therapeutic vaccines will continue into the future.
      Therapeutic vaccines targeting HPVE6 and E7 proteins are actively being pursued
      with new adjuvants and delivery vectors, combined with an improved knowledge of
      the tumour microenvironment, showing great promise. This review will focus on
      recent progress in prophylactic and therapeutic vaccine development and
      implementation since the publication of end of study data from phase III clinical
      trials between 2010 and 2012.

PMID- 25752817
TI  - Nanotechnology in the management of cervical cancer.
AB  - Cervical cancer is a major disease with high mortality. All cervical cancers are
      caused by infection with human papillomaviruses (HPV). Although preventive
      vaccines for cervical cancer are successful, treatment of cervical cancer is far
      less satisfactory because of multidrug resistance and side effects. In this
      review, we summarize the recent application of nanotechnology to the diagnosis
      and treatment of cervical cancer as well as the development of HPV vaccines.
      Early detection of cervical cancer enables tumours to be efficiently removed by
      surgical procedures, leading to increased survival rate. The current method of
      detecting cervical cancer by Pap smear can only achieve 50% sensitivity, whereas
      nanotechnology has been used to detect HPVs with greatly improved sensitivity. In
      cervical cancer treatment, nanotechnology has been used for the delivery of
      anticancer drugs to increase treatment efficacy and decrease side effects.
      Nanodelivery of HPV preventive and therapeutic vaccines has also been
      investigated to increase vaccine efficacy. Overall, these developments suggest
      that nanoparticle-based vaccine may become the most effective way to prevent and
      treat cervical cancer, assisted or combined with some other nanotechnology-based
      therapy.

PMID- 25752818
TI  - Riparian plant community responses to increased flooding: a meta-analysis.
AB  - A future higher risk of severe flooding of streams and rivers has been projected
      to change riparian plant community composition and species richness, but the
      extent and direction of the expected change remain uncertain. We conducted a meta
      analysis to synthesize globally available experimental evidence and assess the
      effects of increased flooding on (1) riparian adult plant and seedling survival,
      (2) riparian plant biomass and (3) riparian plant species composition and
      richness. We evaluated which plant traits are of key importance for the response
      of riparian plant species to flooding. We identified and analysed 53 papers from
      ISI Web of Knowledge which presented quantitative experimental results on
      flooding treatments and corresponding control situations. Our meta-analysis
      demonstrated how longer duration of flooding, greater depth of flooding and,
      particularly, their combination reduce seedling survival of most riparian
      species. Plant height above water level, ability to elongate shoots and
      plasticity in root porosity were decisive for adult plant survival and growth
      during longer periods of flooding. Both 'quiescence' and 'escape' proved to be
      successful strategies promoting riparian plant survival, which was reflected in
      the wide variation in survival (full range between 0 and 100%) under fully
      submerged conditions, while plants that protrude above the water level (>20 cm)
      almost all survive. Our survey confirmed that the projected increase in the
      duration and depth of flooding periods is sufficient to result in species shifts.
      These shifts may lead to increased or decreased riparian species richness
      depending on the nutrient, climatic and hydrological status of the catchment.
      Species richness was generally reduced at flooded sites in nutrient-rich
      catchments and sites that previously experienced relatively stable hydrographs
      (e.g. rain-fed lowland streams). Species richness usually increased at sites in
      desert and semi-arid climate regions (e.g. intermittent streams). 

PMID- 25752814
TI  - Human papillomavirus molecular biology and disease association.
AB  - Human papillomaviruses (HPVs) have evolved over millions of years to propagate
      themselves in a range of different animal species including humans. Viruses that
      have co-evolved slowly in this way typically cause chronic inapparent infections,
      with virion production in the absence of apparent disease. This is the case for
      many Beta and Gamma HPV types. The Alpha papillomavirus types have however
      evolved immunoevasion strategies that allow them to cause persistent visible
      papillomas. These viruses activate the cell cycle as the infected epithelial cell
      differentiates in order to create a replication competent environment that allows
      viral genome amplification and packaging into infectious particles. This is
      mediated by the viral E6, E7, and E5 proteins. High-risk E6 and E7 proteins
      differ from their low-risk counterparts however in being able to drive cell cycle
      entry in the upper epithelial layers and also to stimulate cell proliferation in
      the basal and parabasal layers. Deregulated expression of these cell cycle
      regulators underlies neoplasia and the eventual progression to cancer in
      individuals who cannot resolve high-risk HPV infection. Most work to date has
      focused on the study of high-risk HPV types such as HPV 16 and 18, which has led
      to an understanding of the molecular pathways subverted by these viruses. Such
      approaches will lead to the development of better strategies for disease
      treatment, including targeted antivirals and immunotherapeutics. Priorities are
      now focused toward understanding HPV neoplasias at sites other than the cervix
      (e.g. tonsils, other transformation zones) and toward understanding the
      mechanisms by which low-risk HPV types can sometimes give rise to papillomatosis
      and under certain situations even cancers.

PMID- 25752819
TI  - Protein Kinase C Is Involved in the Induction of ATP-Binding Cassette Transporter
      A1 Expression by Liver X Receptor/Retinoid X Receptor Agonist in Human
      Macrophages.
AB  - The transcription of the ATP-binding cassette transporter A1 (ABCA1) gene, which
      plays a key anti-atherogenic role, is known to be induced by agonists of liver X
      receptors (LXRs). LXRs form obligate heterodimers with retinoid X receptors
      (RXRs) and interact with their recognition sequences in the regulatory regions of
      key genes implicated in the control of cholesterol, fatty acid and glucose
      homeostasis. We have previously shown a novel role for c-Jun N-terminal kinase
      (JNK) and phosphoinositide 3-kinase (PI3K) in the LXRs-mediated induction of
      macrophage gene expression. Protein kinase C (PKC) is often found to regulate the
      action of nuclear receptors and cross talk between this kinase family and JNK
      and/or PI3K has been shown in several settings. We have, therefore, investigated
      a potential role for PKC in the action of LXR/RXR agonist 22-(R)
      hydroxycholesterol (22-(R)-HC)/9-cis-retinoic acid (9cRA) in THP-1 macrophages,
      including the induction of ABCA1 expression. The pan PKC inhibitor
      bisindoylmaleimide was found to attenuate the induction of ABCA1 protein
      expression, the activation of the JNK signaling pathway and the stimulation of
      activator protein-1 (AP-1) DNA binding activity in macrophages treated with 22
      (R)-HC and 9cRA. The role of PKC in the action of these ligands was confirmed
      further by the use of more isotype-specific inhibitors. These studies, therefore,
      reveal a potentially important role for PKC in the action of 22-(R)-HC and 9cRA
      in human macrophages.

PMID- 25752821
TI  - High-Throughput Differentiation and Screening of a Library of Mutant Stem Cell
      Clones Defines New Host-Based Genes Involved in Rabies Virus Infection.
AB  - We used a genomic library of mutant murine embryonic stem cells (ESCs) and report
      the methodology required to simultaneously culture, differentiate, and screen
      more than 3,200 heterozygous mutant clones to identify host-based genes involved
      in both sensitivity and resistance to rabies virus infection. Established
      neuronal differentiation protocols were miniaturized such that many clones could
      be handled simultaneously, and molecular markers were used to show that the
      resultant cultures were pan-neuronal. Next, we used a green fluorescent protein
      (GFP) labeled rabies virus to develop, validate, and implement one of the first
      host-based, high-content, high-throughput screens for rabies virus.
      Undifferentiated cell and neuron cultures were infected with GFP-rabies and live
      imaging was used to evaluate GFP intensity at time points corresponding to
      initial infection/uptake and early and late replication. Furthermore,
      supernatants were used to evaluate viral shedding potential. After repeated
      testing, 63 genes involved in either sensitivity or resistance to rabies
      infection were identified. To further explore hits, we used a completely
      independent system (siRNA) to show that reduction in target gene expression leads
      to the observed phenotype. We validated the immune modulatory gene Unc13d and the
      dynein adapter gene Bbs4 by treating wild-type ESCs and primary neurons with
      siRNA; treated cultures were resistant to rabies infection/replication. Overall,
      the potential of such in vitro functional genomics screens in stem cells adds
      additional value to other libraries of stem cells. This technique is applicable
      to any bacterial or virus interactome and any cell or tissue types that can be
      differentiated from ESCs.

PMID- 25752822
TI  - Simultaneous analysis of Cr(III), Cr(VI), and chromium picolinate in foods using
      capillary electrophoresis-inductively coupled plasma mass spectrometry.
AB  - We herein reported a method for the simultaneous detection of trace Cr(VI),
      Cr(III), and chromium(III) picolinate (CrPic) in foods using CE-ICP-MS together
      with ultrasonic-assisted extraction. The Cr(III) (Cr(3+) ) was chelated with
      trans-1,2-diaminocyclohexane-N,N,N',N'-tetraacetic acid (DCTA) to form a single
      charged Cr-DCTA(-) complex. Then, Cr(VI) (CrO4 (2-) ), Cr-DCTA(-) , and CrPic
      were separated by CE within 8 min under a separation voltage of -13 KV followed
      by their monitoring with ICP mass spectrometer (ICP-MS). The proposed method is
      simple, effective, and sensitive. It has an instrument detection limit of 0.10,
      0.18, and 0.20 ngCr/mL for Cr(VI), Cr(III), and CrPic, respectively. With the
      help of the methods, we have successfully determined Cr(VI), Cr(III), and CrPic
      in nutritional supplement (CrPic yeast tablet) with an RSD (n = 5) <6% and a
      recovery of 93-103%. The experimental results showed that CrPic was the main
      speciation of chromium in the nutritional supplement, with a concentration of
      1514.6 MUg Cr/g. 

PMID- 25752820
TI  - Temperature-sensitive retinoid isomerase activity of RPE65 mutants associated
      with Leber Congenital Amaurosis.
AB  - RPE65 is a membrane-associated retinoid isomerase involved in the visual cycle
      responsible for sustaining vision. Many mutations in the human RPE65 gene are
      associated with distinct forms of retinal degenerative diseases. The pathogenic
      mechanisms for most of these mutations remain poorly understood. Here, we show
      that three Leber congenital amaurosis -associated RPE65 mutants (R91W, Y249C and
      R515W) undergo rapid proteasomal degradation mediated by the 26 S proteasome non
      ATPase regulatory subunit 13 (PSMD13) in cultured human retinal pigment
      epithelium (RPE) cells. These mutant proteins formed cytosolic inclusion bodies
      or high molecular weight complexes via disulfide bonds. The mutations are mapped
      on non-active sites but severely reduced isomerase activity of RPE65. At 30
      degrees C, however, the enzymatic function and membrane-association of the mutant
      RPE65s are significantly rescued possibly due to proper folding. In addition,
      PSMD13 displayed a drastically decreased effect on degradation of the mutant
      proteins in the cells grown at 30 degrees C. These results suggest that PSMD13
      plays a critical role in regulating pathogenicity of the mutations and the
      molecular basis for the PSMD13-mediated rapid degradation and loss of function of
      the mutants is misfolding of RPE65. 

PMID- 25752823
TI  - Can surgeons predict the olfactory outcomes after endoscopic surgery for nasal
      polyposis?
AB  - OBJECTIVES/HYPOTHESIS: The aim of this study is to identify predictors for
      olfactory outcomes in patients with nasal polyposis (NP) after surgery on the
      ethmoidal labyrinths, either with or without resection of the polyps of the
      olfactory cleft (OC). STUDY DESIGN: Prospective study. METHODS: Ninety-six
      patients endoscopically operated on for NP were enrolled in this study. Olfactory
      measurements were performed 1 day prior to surgery and 6 weeks after surgery,
      using odor thresholds and identification tests of the Sniffin' Sticks kit and a 0
      to 10-point visual analog scale. The multivariate logistic regression model was
      also used to assess independent predictors for olfactory outcomes after surgery.
      RESULTS: Twenty-seven patients with preoperative normosmia demonstrated normal
      olfactory function 6 weeks after surgery. Out of 69 patients with preoperative
      hypo-anosmia, 33 patients (47.83%) improved their olfactory function after
      surgery on the basis of the Sniffin' Sticks results. History of previous sinus
      surgery was reported by 77.78% of patients without olfactory improvement and by
      51.52% with olfactory improvement (P = .022). By multivariate analysis, history
      of previous sinus surgery for NP remained a strong predictor of poor olfactory
      outcomes after surgery (adjusted odds ratio = 4.14, 95% confidence interval: 1.29
      13.32, P = .017). Histopathological types of lesions inside the OC as well as the
      resection of moderate/big lesions in the OC were not predictors of olfactory
      outcomes. CONCLUSIONS: The more previous sinus surgeries, the smaller the chance
      for patients to recover their olfactory function after each surgical revision.

PMID- 25752824
TI  - Bilateral cleft lip and palate: A morphometric analysis of facial skeletal form
      using cone beam computed tomography.
AB  - Bilateral cleft lip and palate (BCLP) is caused by a lack of merging of maxillary
      and nasal facial prominences during development and morphogenesis. BCLP is
      associated with congenital defects of the oronasal facial region that can impair
      ingestion, mastication, speech, and dentofacial development. Using cone beam
      computed tomography (CBCT) images, 7- to 18-year old individuals born with BCLP
      (n = 15) and age- and sex-matched controls (n = 15) were retrospectively
      assessed. Coordinate values of three-dimensional facial skeletal anatomical
      landmarks (n = 32) were measured from each CBCT image. Data were evaluated using
      principal coordinates analysis (PCOORD) and Euclidean Distance Matrix Analysis
      (EDMA). PCOORD axes 1-3 explain approximately 45% of the morphological variation
      between samples, and specific patterns of morphological differences were
      associated with each axis. Approximately, 30% of facial skeletal measures
      significantly differ by confidence interval testing (alpha = 0.10) between
      samples. While significant form differences occur across the facial skeleton,
      strong patterns of differences are localized to the lateral and superioinferior
      aspects of the nasal aperture. In conclusion, the BCLP deformity significantly
      alters facial skeletal morphology of the midface and oronasal regions of the
      face, but morphological differences were also found in the upper facial skeleton
      and to a lesser extent, the lower facial skeleton. This pattern of strong
      differences in the oronasal region of the facial skeleton combined with
      differences across the rest of the facial complex underscores the idea that bones
      of the craniofacial skeleton are integrated.

PMID- 25752825
TI  - Taking baby steps in molecular logic-based computation.
AB  - Molecular logic-based computation is a broad umbrella covering molecular sensors
      at its simplest level and logic gate arrays involving steadily increasing levels
      of parallel and serial integration. The fluorescent PET (photoinduced electron
      transfer) switching principle remains a loyal servant of this entire field.
      Applications arise from the convenient operation of molecular information
      processors in very small spaces. 

PMID- 25752826
TI  - Clinical Implications of Femoral Anthropometrical Features for Total Knee
      Arthroplasty in Koreans.
AB  - Anthropometric features of Asians femora and their clinical relevance with regard
      to TKA are not rigorously investigated. We attempted to determine how well
      current prostheses accommodate femoral anthropometric features of Koreans and
      whether the presence of condylar or trochlear overhang or underhang adversely
      affects functional outcomes. We hypothesized that current prostheses do not
      accommodate Korean female femora well, and that overhang or underhang would
      adversely affect outcomes. Condylar and trochlear mediolateral (ML) widths and
      condylar anteroposterior (AP) heights were measured, and ML/AP ratios were
      calculated in 1025 osteoarthritic knees that underwent TKA. Besides gender
      difference, wide individual variation exists in condylar and trochlear widths and
      ML/AP aspect ratios for given AP heights. Size options of current prostheses
      could not cover the wide ranges of ML widths for given AP heights. The knees with
      condylar overhang more than 4mm showed lower maximum flexion angle
      postoperatively (P=0.005). 

PMID- 25752827
TI  - Probing long-lived plasmonic-generated charges in TiO2 /Au by high-resolution X
      ray absorption spectroscopy.
AB  - Exploiting plasmonic Au nanoparticles to sensitize TiO2 to visible light is a
      widely employed route to produce efficient photocatalysts. However, a description
      of the atomic and electronic structure of the semiconductor sites in which
      charges are injected is still not available. Such a description is of great
      importance in understanding the underlying physical mechanisms and to improve the
      design of catalysts with enhanced photoactivity. We investigated changes in the
      local electronic structure of Ti in pure and N-doped nanostructured TiO2 loaded
      with Au nanoparticles during continuous selective excitation of the Au localized
      surface plasmon resonance with X-ray absorption spectroscopy (XAS) and resonant
      inelastic X-ray scattering (RIXS). Spectral variations strongly support the
      presence of long-lived charges localized on Ti states at the semiconductor
      surface, giving rise to new laser-induced low-coordinated Ti sites. 

PMID- 25752828
TI  - Yielding and flow of highly concentrated, few-layer graphene suspensions.
AB  - For a wide range of applications of graphene suspensions, a thorough
      understanding of their rheological properties is crucial. We probe the
      microstructure of dense suspensions of micron-sized, few-layer, defect-free
      graphene platelets by measuring their viscoelastic properties at various
      concentrations up to 39 mg ml(-1). We propose a model to relate the yield strain
      to the mesh size of the microstructure as a function of volume fraction phi. From
      the yield stress measurements we infer the typical bond energy (~20 kBT) and phi
      dependence of the bond number density. These results allow us to express the
      steady shear viscosity for Peclet number Pe < 10 in terms of the platelet
      dimensions, bond energy and phi using a relaxation ansatz. 

PMID- 25752829
TI  - Conditional-ready mouse embryonic stem cell derived macrophages enable the study
      of essential genes in macrophage function.
AB  - The ability to differentiate genetically modified mouse embryonic stem (ES) cells
      into functional macrophages provides a potentially attractive resource to study
      host-pathogen interactions without the need for animal experimentation. This is
      particularly useful in instances where the gene of interest is essential and a
      knockout mouse is not available. Here we differentiated mouse ES cells into
      macrophages in vitro and showed, through a combination of flow cytometry,
      microscopic imaging, and RNA-Seq, that ES cell-derived macrophages responded to
      S. Typhimurium, in a comparable manner to mouse bone marrow derived macrophages.
      We constructed a homozygous mutant mouse ES cell line in the Traf2 gene that is
      known to play a role in tumour necrosis factor-alpha signalling but has not been
      studied for its role in infections or response to Toll-like receptor agonists.
      Interestingly, traf2-deficient macrophages produced reduced levels of
      inflammatory cytokines in response to lipopolysaccharide (LPS) or flagellin
      stimulation and exhibited increased susceptibility to S. Typhimurium infection. 

PMID- 25752830
TI  - Characterization and expression of the cytochrome P450 gene family in diamondback
      moth, Plutella xylostella (L.).
AB  - Cytochrome P450 monooxygenases are present in almost all organisms and can play
      vital roles in hormone regulation, metabolism of xenobiotics and in biosynthesis
      or inactivation of endogenous compounds. In the present study, a genome-wide
      approach was used to identify and analyze the P450 gene family of diamondback
      moth, Plutella xylostella, a destructive worldwide pest of cruciferous crops. We
      identified 85 putative cytochrome P450 genes from the P. xylostella genome,
      including 84 functional genes and 1 pseudogene. These genes were classified into
      26 families and 52 subfamilies. A phylogenetic tree constructed with three
      additional insect species shows extensive gene expansions of P. xylostella P450
      genes from clans 3 and 4. Gene expression of cytochrome P450s was quantified
      across multiple developmental stages (egg, larva, pupa and adult) and tissues
      (head and midgut) using P. xylostella strains susceptible or resistant to
      insecticides chlorpyrifos and fiprinol. Expression of the lepidopteran specific
      CYP367s predominantly occurred in head tissue suggesting a role in either
      olfaction or detoxification. CYP340s with abundant transposable elements and
      relatively high expression in the midgut probably contribute to the
      detoxification of insecticides or plant toxins in P. xylostella. This study will
      facilitate future functional studies of the P. xylostella P450s in
      detoxification. 

PMID- 25752831
TI  - Roles for Histone Acetylation in Regulation of Telomere Elongation and Two-cell
      State in Mouse ES Cells.
AB  - Mammalian telomeres and subtelomeres are marked by heterochromatic epigenetic
      modifications, including repressive DNA methylation and histone methylation
      (e.g., H3K9me3 and H4K20me3). Loss of these epigenetic marks results in increased
      rates of telomere recombination and elongation. Other than these repressive
      epigenetic marks, telomeric and subtelomeric H3 and H4 are underacetylated. Yet,
      whether histone acetylation also regulates telomere length has not been directly
      addressed. We thought to test the effects of histone acetylation levels on
      telomere length using histone deacetylase (HDAC) inhibitor (sodium butyrate, NaB)
      that mediates histone hyperacetylation and histone acetyltransferase (HAT)
      inhibitor (C646) that mediates histone hypoacetylation. We show that histone
      hyperacetylation dramatically elongates telomeres in wild-type ES cells, and only
      slightly elongates telomeres in Terc(-/-) ES cells, suggesting that Terc is
      involved in histone acetylation-induced telomere elongation. In contrast, histone
      hypoacetylation shortens telomeres in both wild-type and Terc(-/-) ES cells.
      Additionally, histone hyperacetylation activates 2-cell (2C) specific genes
      including Zscan4, which is involved in telomere recombination and elongation,
      whereas histone hypoacetylation represses Zscan4 and 2C genes. These data suggest
      that histone acetylation levels affect the heterochromatic state at telomeres and
      subtelomeres, and regulate gene expression at subtelomeres, linking histone
      acetylation to telomere length maintenance.

PMID- 25752832
TI  - Pd-catalyzed difluoromethylation of vinyl bromides, triflates, tosylates, and
      nonaflates.
AB  - Pd-catalyzed difluoromethylation of di-, tri- or tetra-substituted vinyl
      bromides, triflates, tosylates and nonaflates under mild conditions is described.
      The reaction tolerates a wide range of functional groups, such as bromide,
      chloride, fluoride, ester, amine, nitrile, and protected carbonyl, thus providing
      a general route for the preparation of difluoromethylated alkenes. 

PMID- 25752833
TI  - Effects of organic pollution on biological communities of marine biofilm on hard
      substrata.
AB  - We examined the effect of organic enrichment on diatom and bacterial assemblages
      of marine epilithic biofilms on two locations in the Mediterranean, one situated
      in Spain and the other in Greece. Total organic carbon, total organic nitrogen,
      stable isotopes (delta(13)C and delta(15)N) and chlorophyll a indicated
      significant incorporation of organic wastes, increased primary production and
      trophic niche modifications on the biofilms close to the organic enrichment
      source. In Spain, where the organic load was higher than in Greece, diatom and,
      to some extent, bacterial assemblages varied following the organic enrichment
      gradient. The taxonomic richness of diatom and bacterial communities was not
      influenced by organic enrichment. Classical community parameters showed
      consistent patterns to organic pollution in both locations, whereas community
      assemblages were only influenced when organic pollution was greatest. The
      successional patterns of these communities were similar to other epilithic
      communities. The modification of community assemblages induced by organic
      pollution may affect ecological functions. 

PMID- 25752834
TI  - Nephrotic syndrome: Efficacy of rituximab in challenging nephrotic syndrome.
AB  - A new trial provides further evidence that rituximab treatment can reduce the
      risk of relapse in children with steroid-dependent idiopathic nephrotic syndrome.
      Addition of a single infusion of rituximab to steroid therapy was associated with
      a decrease in proteinuria at 3 months and a significant increase in the relapse
      free period.

PMID- 25752836
TI  - Renal injury: KLF6 protects injured podocytes.

PMID- 25752835
TI  - Hypertension: Renal denervation-promising data from the DENERHTN trial.
AB  - In patients with resistant hypertension, renal denervation plus standardized
      stepped-care antihypertensive treatment (SSAHT) resulted in significant blood
      pressure lowering compared with SSAHT alone. These new data from the DENERHTN
      trial may indicate that despite the failure of SYMPLICITY HTN-3, there is light
      at the end of the tunnel for renal denervation.

PMID- 25752837
TI  - Use of hemoglobin A1c as an early predictor of gestational diabetes mellitus.

PMID- 25752838
TI  - Use of hemoglobin A1c as an early predictor of gestational diabetes mellitus.

PMID- 25752839
TI  - Multi-country stem cell trials: The need for an international support structure.

PMID- 25752840
TI  - Abiotic ligation of DNA oligomers templated by their liquid crystal ordering.
AB  - It has been observed that concentrated solutions of short DNA oligomers develop
      liquid crystal ordering as the result of a hierarchically structured
      supramolecular self-assembly. In mixtures of oligomers with various degree of
      complementarity, liquid crystal microdomains are formed via the selective
      aggregation of those oligomers that have a sufficient degree of duplexing and
      propensity for physical polymerization. Here we show that such domains act as
      fluid and permeable microreactors in which the order-stabilized molecular
      contacts between duplex terminals serve as physical templates for their chemical
      ligation. In the presence of abiotic condensing agents, liquid crystal ordering
      markedly enhances ligation efficacy, thereby enhancing its own phase stability.
      The coupling between order-templated ligation and selectivity provided by
      supramolecular ordering enables an autocatalytic cycle favouring the growth of
      DNA chains, up to biologically relevant lengths, from few-base long oligomers.
      This finding suggests a novel scenario for the abiotic origin of nucleic acids. 

PMID- 25752841
TI  - Clinical treatment and prognosis in patients with acute coronary syndrome and
      anemia.

PMID- 25752842
TI  - Sympathetic activity during passive heat stress in healthy aged humans.
AB  - KEY POINTS: Cardiovascular adjustments to heat stress are attenuated in healthy
      aged individuals, which could contribute to their greater prevalence of heat
      related illnesses and deaths during heat waves. The attenuated cardiovascular
      adjustments in the aged could be due to lower increases in sympathetic nerve
      activity during heat stress. We examined muscle sympathetic nerve activity (MSNA)
      and plasma catecholamine concentrations in healthy young and aged individuals
      during whole-body passive heat stress. The main finding of this study is that
      increases in MSNA and plasma catecholamine concentrations did not differ between
      young and aged healthy individuals during passive heating. Furthermore, the
      increase in these variables did not differ when a cold pressor test and lower
      body negative pressure were superimposed upon heating. These findings suggest
      that attenuated cardiovascular adjustments to heat stress in healthy aged
      individuals are unlikely to be related to attenuated increases in sympathetic
      activity. ABSTRACT: Cardiovascular adjustments during heat stress are generally
      attenuated in healthy aged humans, which could be due to lower increases in
      sympathetic activity compared to the young. We compared muscle sympathetic nerve
      activity (MSNA) between 11 young (Y: 28 +/- 4 years) and 10 aged (A: 70 +/- 5
      years) subjects prior to and during passive heating. Furthermore, MSNA responses
      were compared when a cold pressor test (CPT) and lower body negative pressure
      (LBNP) were superimposed upon heating. Baseline MSNA burst frequency (Y: 15 +/- 4
      vs. A: 31 +/- 3 bursts min(-1) , P <= 0.01) and burst incidence (Y: 26 +/- 8 vs.
      A: 50 +/- 7 bursts (100 cardiac cycles (CC))(-1) , P <= 0.01) were greater in the
      aged. Heat stress increased core temperature to a similar extent in both groups
      (Y: +1.2 +/- 0.1 vs. A: +1.2 +/- 0.0 degrees C, P = 0.99). Absolute levels of
      MSNA remained greater in the aged during heat stress (burst frequency: Y: 47 +/-
      6 vs. A: 63 +/- 11 bursts min(-1) , P <= 0.01; burst incidence: Y: 48 +/- 8 vs.
      A: 67 +/- 9 bursts (100 CC)(-1) , P <= 0.01); however, the increase in both
      variables was similar between groups (both P >= 0.1). The CPT and LBNP further
      increased MSNA burst frequency and burst incidence, although the magnitude of
      increase was similar between groups (both P >= 0.07). These results suggest that
      increases in sympathetic activity during heat stress are not attenuated in
      healthy aged humans.

PMID- 25752843
TI  - A Mediterranean-type diet is associated with better metabolic profile in urban
      Polish adults: Results from the HAPIEE study.
AB  - OBJECTIVE: The aim of this study was to evaluate the relationship between
      adherence to a Mediterranean-type diet and metabolic syndrome (MetS) in the
      Polish arm of the Health, Alcohol and Psychosocial factors In Eastern Europe
      (HAPIEE) cohort study. MATERIALS/METHODS: A cross-sectional survey including 8821
      adults was conducted in Krakow, Poland. Food intake was evaluated through a
      validated food frequency questionnaire and adherence to the dietary pattern was
      assessed using a score specifically developed for non-Mediterranean countries
      (MedTypeDiet score). Linear and logistic regression models were performed to
      estimate beta and odds ratios (ORs) and 95% confidence intervals (CIs),
      respectively. RESULTS: Significant associations between the MedTypeDiet score and
      waist circumference (beta=-0.307+/-0.239cm), systolic blood pressure (beta=
      0.440+/-0.428mmHg), and triglycerides (beta=-0.021+/-0.016mmol/L) were observed.
      After multivariable adjustment, individuals in the highest quartile of the score
      were less likely to have MetS, central obesity, high triglycerides, and
      hypertension. Increase of one standard deviation of the score was associated with
      7% less odds of having MetS (OR 0.93, 95% CI: 0.88, 0.97). When analyzing the
      relation of single components of the MedTypeDiet score, wine, dairy products, and
      the total unsaturated:saturated fatty acids ratio were associated with MetS.
      CONCLUSIONS: Adherence to a Mediterranean-like diet may decrease the risk of MetS
      also among non-Mediterranean populations.

PMID- 25752845
TI  - Translational research: Sounds intriguing, but can at times be a frustrating
      endeavor. How can we improve our methodology?

PMID- 25752844
TI  - Validation of a protocol for manual segmentation of the thalamus on magnetic
      resonance imaging scans.
AB  - We present a validated protocol for manual segmentation of the thalamus on T1
      weighted magnetic resonance imaging (MRI) scans using brain image analysis
      software. The MRI scans of five normal control subjects were randomly selected
      from a larger cohort recruited from Lund University Hospital and Landskrona
      Hospital, Sweden. MRIs were performed using a 3.0T Philips MR scanner, with an
      eight-channel head coil, and high resolution images were acquired using a T1
      weighted turbo field echo (T1 TFE) pulse sequence, with resulting voxel size
      1*1*1 mm3. Manual segmentation of the left and right thalami and volume
      measurement was performed on 28-30 contiguous coronal slices, using ANALYZE 11.0
      software. Reliability of image analysis was performed by measuring intra-class
      correlations between initial segmentation and random repeated segmentation of the
      left and right thalami (in total 10 thalami for segmentation); inter-rater
      reliability was measured using volumes obtained by two other experienced tracers.
      Intra-class correlations for two independent raters were 0.95 and 0.98; inter
      class correlations between the expert rater and two independent raters were 0.92
      and 0.98. We anticipate that mapping thalamic morphology in various
      neuropsychiatric disorders may yield clinically useful disease-specific
      biomarkers.

PMID- 25752846
TI  - Clinical protein mass spectrometry.
AB  - Quantitative protein analysis is routinely performed in clinical chemistry
      laboratories for diagnosis, therapeutic monitoring, and prognosis. Today, protein
      assays are mostly performed either with non-specific detection methods or
      immunoassays. Mass spectrometry (MS) is a very specific analytical method
      potentially very well suited for clinical laboratories. Its unique advantage
      relies in the high specificity of the detection. Any protein sequence variant,
      the presence of a post-translational modification or degradation will differ in
      mass and structure, and these differences will appear in the mass spectrum of the
      protein. On the other hand, protein MS is a relatively young technique, demanding
      specialized personnel and expensive instrumentation. Many scientists and opinion
      leaders predict MS to replace immunoassays for routine protein analysis, but
      there are only few protein MS applications routinely used in clinical chemistry
      laboratories today. The present review consists of a didactical introduction
      summarizing the pros and cons of MS assays compared to immunoassays, the
      different instrumentations, and various MS protein assays that have been proposed
      and/or are used in clinical laboratories. An important distinction is made
      between full length protein analysis (top-down method) and peptide analysis after
      enzymatic digestion of the proteins (bottom-up method) and its implication for
      the protein assay. The document ends with an outlook on what type of analyses
      could be used in the future, and for what type of applications MS has a clear
      advantage compared to immunoassays. 

PMID- 25752847
TI  - Development of multiplex mass spectrometric immunoassay for detection and
      quantification of apolipoproteins C-I, C-II, C-III and their proteoforms.
AB  - The impetus for discovery and evaluation of protein biomarkers has been
      accelerated by recent development of advanced technologies for rapid and broad
      proteome analyses. Mass spectrometry (MS)-based protein assays hold great
      potential for in vitro biomarker studies. Described here is the development of a
      multiplex mass spectrometric immunoassay (MSIA) for quantification of
      apolipoprotein C-I (apoC-I), apolipoprotein C-II (apoC-II), apolipoprotein C-III
      (apoC-III) and their proteoforms. The multiplex MSIA assay was fast (~ 40 min)
      and high-throughput (96 samples at a time). The assay was applied to a small
      cohort of human plasma samples, revealing the existence of multiple proteoforms
      for each apolipoprotein C. The quantitative aspect of the assay enabled
      determination of the concentration for each proteoform individually. Low
      abundance proteoforms, such as fucosylated apoC-III, were detected in less than
      20% of the samples. The distribution of apoC-III proteoforms varied among samples
      with similar total apoC-III concentrations. The multiplex analysis of the three
      apolipoproteins C and their proteoforms using quantitative MSIA represents a
      significant step forward toward better understanding of their physiological roles
      in health and disease.

PMID- 25752848
TI  - Comprehensive identification of disulfide bonds using non-specific proteinase K
      digestion and CID-cleavable crosslinking analysis methodology for Orbitrap LC/ESI
      MS/MS data.
AB  - Disulfide bonds are valuable constraints in protein structure modeling. The Cys
      Cys disulfide bond undergoes specific fragmentation under CID and, therefore, can
      be considered as a CID-cleavable crosslink. We have recently reported on the
      benefits of using non-specific digestion with proteinase K for inter-peptide
      crosslink determination. Here, we describe an updated application of our CID
      cleavable crosslink analysis software and our crosslinking analysis with non
      specific digestion methodology for the robust and comprehensive determination of
      disulfide bonds in proteins, using Orbitrap LC/ESI-MS/MS data. 

PMID- 25752849
TI  - Macular pigment carotenoids in the retina and occipital cortex are related in
      humans.
AB  - OBJECTIVES: Lutein and zeaxanthin are dietary carotenoids that preferentially
      accumulate in the macular region of the retina. Together with meso-zeaxanthin, a
      conversion product of lutein in the macula, they form the macular pigment. Lutein
      is also the predominant carotenoid in human brain tissue and lutein status is
      associated with cognitive function in adults. The study objective was to evaluate
      the relationship between retinal and brain lutein and zeaxanthin in humans.
      METHODS: Donated brain tissue (occipital cortex and hippocampus) and matched
      retina were obtained from the National Disease Research Interchange, a national
      human tissue resource center which adheres to strict consent and confidentiality
      procedures. Decedents were men and women aged >50 years who either had normal
      cognitive function or Alzheimer's disease. Tissues were analyzed using standard
      lipid extractions followed by analysis on reverse-phase high performance liquid
      chromatography (HPLC) and normal-phase HPLC (for meso-zeaxanthin). RESULTS:
      Macular pigment carotenoids (lutein, meso-zeaxanthin, and zeaxanthin combined) in
      the retina were significantly related to the combined concentrations of lutein
      and zeaxanthin in the occipital cortex. When analyzed separately, only retinal
      lutein (plus meso-zeaxanthin), not zeaxanthin, was significantly related to
      lutein in the occipital cortex. No correlations were observed with lutein and
      zeaxanthin in the hippocampus. DISCUSSION: Total macular pigment density measured
      via non-invasive, psychophysical techniques can be used as a biomarker to
      ascertain brain lutein and zeaxanthin status in clinical studies.

PMID- 25752850
TI  - Group C Streptococcus dysgalactiae subsp. equisimilis in south-east Brazil:
      genetic diversity, resistance profile and the first report of human and equine
      isolates belonging to the same multilocus sequence typing lineage.
AB  - Streptococcus dysgalactiae subsp. equisimilis (SDSE) isolates are the most common
      group C streptococci in humans and reports of invasive infections associated with
      SDSE have been increasing. Molecular epidemiology studies are an important
      strategy to trace the emergence and spread of possible well-fit bacterial
      pathogens of humans and animals. In this work, we analysed the antimicrobial and
      clonal profiles of 115 SDSE infection and colonization isolates of human and
      equine origin. PFGE revealed the spread of two main clusters: clone A (57.4%) and
      clone A (26.1%). Remarkably, two isolates from clone B obtained from human
      colonization cases displayed identical PFGE patterns to those of three equine
      infection isolates. In addition, multilocus sequence typing allocated these
      isolates to ST129 (CC31). All of the SDSE isolates were susceptible to
      penicillin, vancomycin, gentamicin, levofloxacin and chloramphenicol.
      Tetracycline and erythromycin resistance rates were 65.2 and 13.9% respectively.
      Nevertheless, none of the isolates displaying sporadic PFGE patterns showed
      erythromycin resistance. The majority of erythromycin-resistant isolates from
      clone A had inducible resistance to macrolides, lincosamines and streptogramins B
      (iMLSB phenotype), which is associated with the presence of the ermA gene,
      whereas the resistant isolates from clone B showed the M phenotype, associated
      with the mefA gene. In conclusion, the data indicated that the analysed
      collection of SDSE isolates displayed a clonal structure and that the isolates
      found in human colonization cases could also be involved in equine infections.

PMID- 25752851
TI  - Analysis of the relationship between invasive capability of Helicobacter pylori
      and gastroduodenal diseases.
AB  - Helicobacter pylori (H. pylori) may enter into host cells, maybe as a facultative
      intracellular pathogen. This study aims to reveal the roles of internalized H.
      pylori in the bacterial pathopoiesis. Transmission electron microscopy was used
      to observe the invasion of H. pylori. Invasion rates of H. pylori (two standard
      strains and 43 clinical strains) were examined by gentamicin invasion assay. The
      cagA, cagE and vacA genes of H. pylori were detected by PCR. The cagA 3'region
      (cagA-EPIYA) of each strain was sequenced. The secretion of IL-8 from AGS cells
      and activity of NF-kappaB induced by intracellular H. pylori were tested by ELISA
      and the dual-luciferase reporter assay system, respectively. It was found that H.
      pylori could adhere to and invade AGS cells, then continue to survive and
      multiply in the cytoplasm. The average invasion rate of H. pylori gastric cancer
      plants and that of ulcer plants were both higher than that of gastritis plants (P
      ~ 0.0001). In the clinical strains, cagA, vacA and cagE were all positive; cagA
      EPIYA genotypes included ABD 90.7% (39/43) and ABBD 9.3% (4/43), all without
      comparability. Notably, the average invasion rate of H. pylori vacA s1c-i1-m1b
      plants was higher than that of vacA s1c-i1-m2 plants (P=0.0445). In addition, the
      intracellular H. pylori all could induce IL-8 secretion, which was decreased
      after cells were pretreated with anti-beta1-integrin antibody or SN-50 (an NF
      kappaB inhibitor). The intracellular H. pylori all activated NF-kappaB, which
      would be inhibited after cells were pretreated with anti-beta1-integrin antibody.
      These results demonstrate that H. pylori invasive ability and disease severity
      have a positive correlation, and this intension of invasive ability is associated
      with the vacA mid-region, not with cagA, cagA-EPIYA or cagE. It is possible that
      cagA and cagE are essential for the bacterial invasion. Internalized H. pylori
      can activate NF-kappaB signal pathway and induce IL-8 secretion, which suggests
      that H. pylori invasion may be an important strategy to play a role in the
      development of H. pylori associated diseases.

PMID- 25752852
TI  - Validation of western Helicobacter pylori IgG antibody assays in Korean adults.
AB  - Helicobacter pylori infection is endemic in Korea, and serology testing is widely
      performed. The aim of this study was to validate and compare the diagnostic
      accuracy of Korean and Western serological assays for H. pylori detection in
      Korean adults. The 114 Korean adults who visited our centre over a 6-month period
      for the evaluation of H. pylori infection using the urea breath test (UBT) were
      enrolled in this prospective study. Anti-H. pylori IgG was measured using three
      commercially available immunoassays: Genedia H. pylori ELISA (Green Cross Medical
      Science), Chorus helicobacter IgG (DIESSE Diagnostica Senese) and Vidas H. pylori
      IgG (bioMerieux). Positive UBT findings were obtained in 40.6% of included
      subjects. The sensitivities and the specificities of Vidas, Chorus and Genedia
      were 89.7%, 100% and 100% and 85.5%, 75.4% and 80.7%, respectively. We found no
      differences in sensitivity between the Vidas and Chorus (P=0.125), Chorus and
      Genedia (P=0.125) and Vidas and Genedia (P=1.000) assays. There were also no
      differences in specificity between the Vidas and Chorus (P=0.070), Chorus and
      Genedia (P=0.508) and Vidas and Genedia (P=0.549) assays. In Korean adults, the
      Genedia H. pylori ELISA, Chorus helicobacter IgG and Vidas H. pylori IgG assays
      exhibited a high concurrence rate with similar diagnostic accuracy. Thus, both
      the Korean and Western non-invasive assays are reliable for serodiagnosis of H.
      pylori in Korean individuals.

PMID- 25752853
TI  - Emergence in Taiwan of novel norovirus GII.4 variants causing acute
      gastroenteritis and intestinal haemorrhage in children.
AB  - Norovirus is the leading cause of viral gastroenteritis globally. Norovirus
      genotype GII.4 is responsible for the majority of outbreaks, but new variants are
      continuously emerging. The objective of the study was to delineate the clinical
      manifestations and complications associated with these new norovirus GII.4
      variants in children. We investigated norovirus infections from the community
      outbreak in October 2011-September 2012 and an earlier outbreak in 2006-2007, in
      northern Taiwan. Norovirus genotypes and their variants were validated using
      molecular methods. A norovirus outbreak started in mid-2011 and continued through
      2012 in northern Taiwan. Hospitalized children infected by norovirus in 2012
      showed a significantly higher incidence of intestinal haemorrhage, as indicated
      by grossly bloody faeces (P=0.012) and occult blood in faeces (P < 0.001), and
      also presented with more high fever >39  degrees C (P < 0.001), fever >38.5 
      degrees C (P < 0.001) and fever of any temperature >38  degrees C (P < 0.001),
      compared with children hospitalized in 2006-2007. Analysis of 20 near-full-length
      genome sequences indicated an emergence of GII.4 2012 variants in 2011-2012.
      Circulating noroviruses can be divided into two clusters: GII.4 2012a, which is
      identical to the newly reported strain GII.4 Sydney 2012, and GII.4 2012b, which
      is close to GII.4 2006b, the earlier predominant strain. The emerging new
      variants of norovirus GII.4 caused a distinct clinical syndrome of acute
      gastroenteritis with severe fever and a high rate of intestinal haemorrhage in
      children. The genetic diversity associated with changing clinical manifestations
      poses major obstacles to norovirus control.

PMID- 25752856
TI  - Concave microwell array-mediated three-dimensional tumor model for screening
      anticancer drug-loaded nanoparticles.
AB  - We investigated the effect of anticancer drug-loaded functional polymeric
      nanoparticles on drug resistance of three-dimensional (3D) breast tumor
      spheroids. 3D tumor models were built using concave microwells with different
      diameters (300-700MUm) and nanoparticles were prepared using thermo-responsive
      poly(N-isopropylacrylamide) (PNIPAM)-co-acrylic acid (AA). Upon culturing with
      doxorubicin-loaded PNIPAM-co-AA nanoparticles for 96hours, the smallest tumor
      spheroids were extensively disrupted, resulting in a reduction in spheroid
      diameter. In contrast, the sizes of the largest tumor spheroids were not changed.
      Scanning electron microscopy revealed that the circular shape of 3D spheroids
      treated with doxorubicin-loaded PNIPAM-co-AA nanoparticles had collapsed
      severely. Cell viability assays also demonstrated that the largest tumor
      spheroids cultured with doxorubicin-loaded PNIPAM-co-AA nanoparticles were highly
      resistant to the anticancer drug. We confirmed that tight cell-cell contacts
      within largest tumor spheroids significantly improved the anticancer drug
      resistance. Therefore, this uniform-sized 3D breast tumor model could be a
      potentially powerful tool for anticancer drug screening applications. FROM THE
      CLINICAL EDITOR: The battle against cancer is a big challenge. With new anti
      cancer drugs being developed under the nanotechnology platform, there is a need
      to have a consistent and reliable testing system that mimics the in-vivo tumor
      scenario. The authors successfully designed a 3D tumor model using concave
      microwells to produce different tumor diameters. This will be of value for future
      drug screening.

PMID- 25752854
TI  - Co-infection of the Siberian hamster (Phodopus sungorus) with a novel
      Helicobacter sp. and Campylobacter sp.
AB  - We report the isolation of a novel helicobacter isolated from the caecum of the
      Siberian hamster (Phodopus sungorus). Sequence analysis showed 97% sequence
      similarity to Helicobacter ganmani. In addition, we report the co-infection of
      these Siberian hamsters with a Campylobacter sp. and a second Helicobacter sp.
      with 99% sequence similarity to Helicobacter sp. flexispira taxon 8 (Helicobacter
      bilis), a species isolated previously from patients with bacteraemia. Gross
      necropsy and histopathology did not reveal any overt pathological lesions of the
      liver and gastrointestinal tract that could be attributed to the Helicobacter or
      Campylobacter spp. infections. This is the first helicobacter to be identified in
      the Siberian hamster and the first report of co-infection of Helicobacter spp.
      and Campylobacter sp. in asymptomatic Siberian hamsters.

PMID- 25752855
TI  - Protein transfer-mediated surface engineering to adjuvantate virus-like
      nanoparticles for enhanced anti-viral immune responses.
AB  - Recombinant virus-like nanoparticles (VLPs) are a promising nanoparticle platform
      to develop safe vaccines for many viruses. Herein, we describe a novel and rapid
      protein transfer process to enhance the potency of enveloped VLPs by decorating
      influenza VLPs with exogenously added glycosylphosphatidylinositol-anchored
      immunostimulatory molecules (GPI-ISMs). With protein transfer, the level of GPI
      ISM incorporation onto VLPs is controllable by varying incubation time and
      concentration of GPI-ISMs added. ISM incorporation was dependent upon the
      presence of a GPI-anchor and incorporated proteins were stable and functional for
      at least 4weeks when stored at 4 degrees C. Vaccinating mice with GPI-granulocyte
      macrophage colony-stimulating factor (GM-CSF)-incorporated-VLPs induced stronger
      antibody responses and better protection against a heterologous influenza virus
      challenge than unmodified VLPs. Thus, VLPs can be enriched with ISMs by protein
      transfer to increase the potency and breadth of the immune response, which has
      implications in developing effective nanoparticle-based vaccines against a broad
      spectrum of enveloped viruses. FROM THE CLINICAL EDITOR: The inherent problem
      with current influenza vaccines is that they do not generate effective cross
      protection against heterologous viral strains. In this article, the authors
      described the development of virus-like nanoparticles (VLPs) as influenza
      vaccines with enhanced efficacy for cross-protection, due to an easy protein
      transfer modification process.

PMID- 25752857
TI  - Tumour stromal morphology impacts nanomedicine cytotoxicity in patient-derived
      xenografts.
AB  - It is challenging to evaluate how tumour pathophysiology influences nanomedicine
      therapeutic effect; however, this is a key question in drug delivery. An advanced
      analytical method was developed to quantify the spatial distribution of drug
      induced effect in tumours with varied stromal morphologies. The analysis utilises
      standard immunohistochemistry images and quantifies the frequency of positive
      staining as a function of distance from the stroma. Two stromal morphologies -
      Estuary and Tumour Island - were classified in 28 tumours from a lung cancer
      explant model in mice treated with liposomal doxorubicin. Analysis demonstrated
      that Estuary-like tumours presented a highly convoluted tumour-stroma interface,
      with most tumour cells in close proximity to vessels; these tumours were 8.8-fold
      more responsive to liposomal doxorubicin than were Tumour Island-like tumours,
      which were nearly unresponsive to liposomal doxorubicin. SDARS analysis allows
      the relative treatment effect to be assessed in tumours individually, and enables
      investigation of nanomedicine delivery in complex tumour pathophysiologies. FROM
      THE CLINICAL EDITOR: Advances in nanotechnology have brought about many novel
      treatment modalities for cancer. Nonetheless, there is no standard evaluation
      technique for tumor cells' drug response. The authors here utilized patient
      derived tumour xenograft (PDTX) models to have a more translatable pre-clinical
      evaluation platform for nanomedicine drugs. They then used advanced imaging
      acquisition technique to analyze tumor stromal morphology, which they named
      Spatial Distribution of Apoptosis Relative to Stroma (SDARS). The findings would
      have significant clinical impact as it would help predict the eventual clinical
      drug response.

PMID- 25752858
TI  - Expression of cyclooxygenase-2 in the mammary gland tissue of goats affected with
      caprine contagious agalactia.
AB  - Caprine contagious agalactia is a syndrome most frequently caused by Mycoplasma
      agalactiae. The pathogenic mechanisms that allow M. agalactiae to persist in the
      mammary gland tissues following infection, despite a prominent inflammatory
      response, are yet to be fully established. The aim of the present study was to
      investigate cyclooxygenase (COX)-2 in the mammary gland of goats during M.
      agalactiae infection. COX-2 expression was evaluated by immunohistochemistry in
      the inflammatory lesions of 10 goats affected with M. agalactiae-induced mastitis
      (five naturally infected and five experimentally infected). Epithelial cells,
      macrophages, endothelial cells, fibroblasts and, to a lesser extent, neutrophils
      demonstrated positive immunostaining for COX-2, associated with areas of mastitis
      and with the presence of M. agalactiae antigen. These research findings suggest
      that COX-2 is involved in the inflammatory response that occurs in caprine
      contagious agalactia.

PMID- 25752859
TI  - Refining the hypothesis of a complete diet.

PMID- 25752861
TI  - Using hyperspectral imaging to determine germination of native Australian plant
      seeds.
AB  - We investigated the ability to accurately and non-destructively determine the
      germination of three native Australian tree species, Acacia cowleana Tate
      (Fabaceae), Banksia prionotes L.F. (Proteaceae), and Corymbia calophylla (Lindl.)
      K.D. Hill & L.A.S. Johnson (Myrtaceae) based on hyperspectral imaging data. While
      similar studies have been conducted on agricultural and horticultural seeds, we
      are unaware of any published studies involving reflectance-based assessments of
      the germination of tree seeds. Hyperspectral imaging data (110 narrow spectral
      bands from 423.6nm to 878.9nm) were acquired of individual seeds after 0, 1, 2,
      5, 10, 20, 30, and 50days of standardized rapid ageing. At each time point, seeds
      were subjected to hyperspectral imaging to obtain reflectance profiles from
      individual seeds. A standard germination test was performed, and we predicted
      that loss of germination was associated with a significant change in seed coat
      reflectance profiles. Forward linear discriminant analysis (LDA) was used to
      select the 10 spectral bands with the highest contribution to classifications of
      the three species. In all species, germination decreased from over 90% to below
      20% in about 10-30days of experimental ageing. P50 values (equal to 50%
      germination) for each species were 19.3 (A. cowleana), 7.0 (B. prionotes) and
      22.9 (C. calophylla) days. Based on independent validation of classifications of
      hyperspectral imaging data, we found that germination of Acacia and Corymbia
      seeds could be classified with over 85% accuracy, while it was about 80% for
      Banksia seeds. The selected spectral bands in each LDA-based classification were
      located near known pigment peaks involved in photosynthesis and/or near spectral
      bands used in published indices to predict chlorophyll or nitrogen content in
      leaves. The results suggested that seed germination may be successfully
      classified (predicted) based on reflectance in narrow spectral bands associated
      with the primary metabolism function and performance of plants. 

PMID- 25752862
TI  - Evaluation of fall Sun Exposure Score in predicting vitamin D status in young
      Canadian adults, and the influence of ancestry.
AB  - Query of sun-related habits or ancestry could help screen for risk of vitamin D
      insufficiency (serum 25-hydroxyvitamin D<75nmol/L). We evaluated the association
      between Sun Exposure Score (calculated from recall of Time Exposed to Sun and
      Skin Exposed to Sun in the previous week), demographics and anthropometrics
      (including self-reported ancestry and skin melanin reflectometry), and serum
      25(OH)D levels in healthy young Canadian adults in the Greater Toronto Area (GTA;
      43 degrees N) during fall. 310 adults (67% female) of European, East Asian, and
      South Asian ancestries were evaluated. The median (interquartile range) 25(OH)D
      level was 49.7nmol/L (36.7-70.3) and 80% of participants were vitamin D
      insufficient. The vast majority of those of East and South Asian ancestry were
      vitamin D insufficient (91% and 97%, respectively), as were 55% of those of
      European ancestry. Sun Exposure Score and 25(OH)D concentrations were not
      associated after accounting for confounders. A multivariable model showed
      ancestry, recent summer sun exposure, sex, melanin, vitamin D intake, age and
      year of study significantly predicted 25(OH)D concentration; ancestry was the
      strongest independent predictor (adjusted R(2)=43%). Although Sun Exposure Score
      was not a significant predictor of serum 25(OH)D levels, inquiry of ancestry has
      potential use in screening for vitamin D insufficiency. 

PMID- 25752863
TI  - [Consensus on the detection and management of prediabetes. Consensus and Clinical
      Guidelines Working Group of the Spanish Diabetes Society].
AB  - In Spain, according to the Di@bet.es study, 13.8% of the adult population suffers
      from diabetes and 14.8% from some form of prediabetes (impaired glucose
      tolerance, impaired fasting glucose or both). Since early detection of
      prediabetes can facilitate the implementation of therapeutic measures to prevent
      its progression to diabetes, we believe that preventive strategies in primary
      care and specialized clinical settings should be agreed. Screening for diabetes
      and prediabetes using a specific questionnaire (FINDRISC) and/or the measurement
      of fasting plasma glucose in high risk patients leads to detecting patients at
      risk of developing diabetes and it is necessary to consider how they should be
      managed. The intervention in lifestyle can reduce the progression to diabetes and
      reverse a prediabetic state to normal and is a cost-effective intervention. Some
      drugs, such as metformin, have also been shown effective in reducing the
      progression to diabetes but are not superior to non-pharmacological
      interventions. Finally, an improvement in some cardiovascular risk factors has
      been observed although there is no strong evidence supporting the effectiveness
      of screening in terms of morbility and mortality. The Consensus and Clinical
      Guidelines Working Group of the Spanish Diabetes Society has issued some
      recommendations that have been agreed by the Sociedad Espanola de Endocrinologia
      y Nutricion, Sociedad Espanola de Endocrinologia Pediatrica, Sociedad Espanola de
      Farmacia Comunitaria, Sociedad Espanola de Medicina Familiar y Comunitaria,
      Sociedad Espanola de Medicos Generales, Sociedad Espanola de Medicos de Atencion
      Primaria, Sociedad Espanola de Medicina Interna, Asociacion de Enfermeria
      Comunitaria and Red de Grupos de Estudio de la Diabetes en Atencion Primaria. 

PMID- 25752864
TI  - [Prediagnostic presentations of Parkinson's disease in primary care: A case
      control study].

PMID- 25752865
TI  - Dissecting the time course of person recognition in natural viewing environments.
AB  - Person recognition often unfolds over time and distance as a person approaches,
      with the quality of identity information from faces, bodies, and motion in
      constant flux. Participants were familiarized with identities using close-up and
      distant videos. Recognition was tested with videos of people approaching from a
      distance. We varied the timing of prompted responses in the test videos, the
      amount of video seen, and whether the face, body, or whole person was visible. A
      free response condition was also included to allow participants to respond when
      they felt 'confident'. The pattern of accuracy across conditions indicated that
      recognition judgments were based on the most recently available information, with
      no contribution from qualitatively diverse and statistically useful person cues
      available earlier in the video. Body recognition was stable across viewing
      distance, whereas face recognition improved with proximity. The body made an
      independent contribution to recognition only at the farthest distance tested.
      Free response latencies indicated meta-knowledge of the optimal proximity for
      recognition from faces versus bodies. Notably, response bias varied strongly as a
      function of participants' expectation about whether closer proximity video was
      forthcoming. These findings lay the groundwork for developing person recognition
      theories that generalize to natural viewing environments. 

PMID- 25752866
TI  - Integrating sequencing batch reactor with bio-electrochemical treatment for
      augmenting remediation efficiency of complex petrochemical wastewater.
AB  - The present study evaluates the sequential integration of two advanced biological
      treatment methods viz., sequencing batch reactor (SBR) and bioelectrochemical
      treatment systems (BET) for the treatment of real-field petrochemical wastewater
      (PCW). Initially two SBR reactors were operated in aerobic (SBR(Ae)) and anoxic
      (SBR(Ax)) microenvironments with an organic loading rate (OLR) of 9.68 kg
      COD/m(3)-day. Relatively, SBR(Ax) showed higher substrate degradation (3.34 kg
      COD/m(3)-day) compared to SBR(Ae) (2.9 kg COD/m(3)-day). To further improve
      treatment efficiency, the effluents from SBR process were fed to BET reactors.
      BET(Ax) depicted higher SDR (1.92 kg COD/m(3)-day) with simultaneous power
      generation (17.12 mW/m(2)) followed by BET(Ae) (1.80 kg COD/m(3)-day; 14.25
      mW/m(2)). Integrating both the processes documented significant improvement in
      COD removal efficiency due to the flexibility of combining multiple
      microenvironments sequentially. Results were supported with GC-MS and FTIR, which
      confirmed the increment in biodegradability of wastewater.

PMID- 25752867
TI  - Sparse serological evidence of H5N1 avian influenza virus infections in domestic
      cats, northeastern China.
AB  - Today the cross-species transmission of avian influenza viruses (AIV) are a great
      concern. A number of AIV strains are now enzootic among poultry, with H9N2 and
      highly pathogenic H5N1 AIV strains prevalent in China. H5N1 strains have been
      recognized to infect zoo and domestic feline species. In this serological study
      we sought to examine evidence that H5N1 strains have infected domestic cats in
      northeastern China. In 2013, we conducted a cross-sectional serological study of
      916 healthy cats in Heilongjian, Jilin, and Liaonin Provinces. Sera were screened
      with a hemagglutinin inhibition (HI) assay and seropositive specimens (HI >=
      1:20) were further evaluated with a microneutralization (MN) assay against a
      clade 2.3.2 H5N1 AIV, a H9N2 AIV, A (H1N1)pdm09, and a canine H3N2 virus. While
      ~2% of cats had elevated HI assays against H5N1, no elevations were confirmed (MN
      >= 1:80). These data serve as baseline for future surveillance for AIV infections
      among domestic cats. Conducting such surveillance seems important for
      geographical areas recognized as endemic for AIVs. This is especially true for
      countries such as China where domestic cats and poultry are often in close
      contact.

PMID- 25752868
TI  - Employment status among non-retired cancer survivors in Japan.
AB  - Employed cancer patients confront some challenges as they attempt to return to
      work after treatment. We aimed to identify correlates of return to work for
      cancer survivors in Japan, with an emphasis on employment status. Participants
      were 260 patients (aged <65 years) who had received a cancer diagnosis >= 1 year
      previously and who were employed at the time of diagnosis. Participants completed
      questionnaires at consultations at any Regional Cancer Center Hospitals in
      Yamagata, Japan between 28 November 2011 and 9 December 2011. Logistic regression
      analysis was used to identify correlates of return to work. Data cross-tabulation
      was used to evaluate relationships to workplace and income-changes by employment
      status. A high proportion of patients (75.8%) had returned to work. Non-regularly
      employed survivors were less likely to return to work (odds ratio = 5.03; 95%
      confidence interval, 1.18-21.35). Individuals with poor health, advanced-stage
      tumours, of advanced age and women were significantly less likely to return to
      work. Only 52.8% of non-regular employees continued to be employed, and their
      income decreased by as much as 61.1%. Social and financial support policies
      should be organised based on more intensive study of employment circumstances.

PMID- 25752870
TI  - The role of short courses in Australasian emergency medicine training.

PMID- 25752869
TI  - The impact of prenatal alcohol exposure on hippocampal-dependent outcome measures
      is influenced by prenatal and early-life rearing conditions.
AB  - BACKGROUND: The clinical course of individuals exposed to alcohol in utero is
      influenced by multiple factors, including the social environments of the gravid
      female and offspring. In the present studies we focused on the effects of
      prenatal alcohol exposure (PAE) and the prenatal and early-life social
      environments on the hippocampal formation, as impaired development and
      functioning of this brain region have been implicated in several of the adverse
      cognitive outcomes associated with PAE. METHODS: We combined our PAE mouse model
      with 2 conditions of housing pregnant dams and their preweanling offspring: the
      standard nest (SN), in which a dam is individually housed prior to parturition
      and then remains isolated with her offspring, and the communal nest (CN), in
      which multiple dams are housed together prior to parturition and then following
      delivery the moms and their litters share a nest. Mouse dams consumed either 10%
      (w/v) ethanol in 0.066% (w/v) saccharin (SAC) or 0.066% (w/v) SAC alone using a
      limited (4-hour) access, drinking-in-the-dark paradigm. Immunoblotting techniques
      were used to measure levels of the glucocorticoid receptor (GR), 11-beta
      hydroxysteroid dehydrogenase 1, the FK506-binding proteins 51 and 52, and
      corticotropin-releasing hormone receptor type 1 in the hippocampal formation
      isolated from male adolescent offspring. We also determined the effect of PAE and
      rearing conditions on context discrimination, a hippocampal-dependent
      learning/memory task. RESULTS: SN PAE offspring displayed impaired context
      discrimination and neurochemical changes in the hippocampal formation consistent
      with increased GR nuclear localization. These effects of PAE were, in general,
      ameliorated in mice reared in a CN. The CN also altered neurochemical measures
      and improved learning/memory in SAC control animals. CONCLUSIONS: These studies
      demonstrate a complex interplay between the effects of PAE and social
      environments. The findings have important translational implications, as well as
      highlight the importance of considering rearing conditions in the interpretation
      of research findings on PAE.

PMID- 25752871
TI  - Wetting of mono and few-layered WS2 and MoS2 films supported on Si/SiO2
      substrates.
AB  - The recent interest and excitement in graphene has also opened up a pandora's box
      of other two-dimensional (2D) materials and material combinations which are now
      beginning to come to the fore. One family of these emerging 2D materials is
      transition metal dichalcogenides (TMDs). So far there is very limited
      understanding on the wetting behavior of "monolayer" TMD materials. In this
      study, we synthesized large-area, continuous monolayer tungsten disulfide (WS2)
      and molybdenum disulfide (MoS2) films on SiO2/Si substrates by the thermal
      reduction and sulfurization of WO3 and MO3 thin films. The monolayer TMD films
      displayed an advancing water contact angle of ~83 degrees  as compared to ~90
      degrees  for the bulk material. We also prepared bilayer and trilayer WS2 films
      and studied the transition of the water contact angle with increasing number of
      layers. The advancing water contact angle increased to ~85 degrees  for the
      bilayer and then to ~90 degrees  for the trilayer film. Beyond three layers,
      there was no significant change in the measured water contact angle. This type of
      wetting transition indicates that water interacts to some extent with the
      underlying silica substrate through the monolayer TMD sheet. The experimentally
      observed wetting transition with numbers of TMD layers lies in-between the
      predictions of one continuum model that considers only van der Waals attractions
      and another model that considers only dipole-dipole interactions. We also
      explored wetting as a function of aging. A clean single-layer WS2 film (without
      airborne contaminants) was shown to be strongly hydrophilic with an advancing
      water contact angle of ~70 degrees . However, over time, the sample ages as
      hydrocarbons and water present in air adsorb onto the clean WS2 sheet. After ~7
      days, the aging process is completed and the advancing water contact angle of the
      aged single-layer WS2 film stabilizes at ~83 degrees . These results suggest that
      clean (i.e., nonaged) monolayer TMDs are hydrophilic materials. We further show
      that substitution of sulfur atoms by oxygen in the lattice of aged monolayer WS2
      and MoS2 films can be used to generate well-defined 'hydrophobic-hydrophilic'
      patterns that preferentially accumulate and create microdrop arrays on the
      surface during water condensation and evaporation experiments. 

PMID- 25752872
TI  - The Research Hospitalist: Protocol Enabler and Protector of Participant Safety.

PMID- 25752873
TI  - Brief counseling for tobacco cessation in dental clinics: A toothless
      intervention?

PMID- 25752874
TI  - The complexity model: a novel approach to improve chronic pain care.
AB  - OBJECTIVE: More than 25% of the US population experiences chronic pain; yet few
      physicians specialize in the field of pain medicine. This article will review a
      theoretical model of care that stratifies treatment and patients by level and
      type of complexity and promotes communication between specialist and primary care
      providers. DISCUSSION: The undertreatment of pain was recently brought to
      national attention to encourage both clinicians and patients to advocate for
      improved pain care. The specialty of pain medicine and models of care, challenges
      of managing pain in a primary care setting, and the reliance on an opioid-focused
      approach are reviewed. An evolved model of pain care based on the complexity of
      pain and emphasizing a dynamic collaboration between the primary care provider
      and the pain specialist is discussed. CONCLUSIONS: From the perspective of the
      busy clinician, the treatment of chronic pain can be overwhelming. The scarcity
      of trained pain practitioners and the burgeoning number of patients with chronic
      pain necessitate a new approach that values the complex nature of chronic pain
      and offers a practical blueprint to meet these challenges.

PMID- 25752875
TI  - Outcomes of dose-adjusted Berlin-Frankfurt-Munster-90 regimen without
      radiotherapy in adolescents and adults with T cell lymphoblastic lymphoma.
AB  - The aim of this study was to evaluate the outcomes using the dose-adjusted Berlin
      Frankfurt-Munster (BFM-90) regimen without radiotherapy in adolescents and adults
      with T cell lymphoblastic lymphoma (T-LBL) at Beijing Cancer Hospital. Between
      March 2004 and December 2013, 57 newly diagnosed T-LBL patients were treated in
      our center. We retrospectively analyzed their main clinical characteristics and
      prognosis. The media age of the patients at diagnosis was 26 (range 14-54). At a
      median follow-up of 24 months (range 5-119), 38 patients (67 %) were alive. The
      estimated 3-year overall survival (OS) rate and progression-free survival (PFS)
      rate were 64 and 60 %, respectively. Abnormal WBC at diagnosis, high IPI and no
      early response were indicated as adverse prognostic factors for both PFS and OS
      (p < 0.05). There was also a trend for better survival in autologous peripheral
      blood stem cell transplantation (APBSCT) group as compared to non-APBSCT group (3
      year OS 83 vs. 57 %), but without any significant difference. This study
      suggested that the dose-adjusted BFM-90 protocol without irradiation showed
      comparable long-term results in Chinese adolescents and adults with T-LBL. APBSCT
      may become a choice whether we can identify the best candidate.

PMID- 25752876
TI  - The problem of pulmonary embolism diagnosis in pregnancy.

PMID- 25752877
TI  - Duchenne muscular dystrophy.
AB  - Duchenne muscular dystrophy, an X-linked disorder, has an incidence of one in
      5000 boys and presents in early childhood with proximal muscle weakness.
      Untreated boys become wheelchair bound by the age of 12 years and die of
      cardiorespiratory complications in their late teens to early 20s. The use of
      corticosteroids, non-invasive respiratory support, and active surveillance and
      management of associated complications have improved ambulation, function,
      quality of life and life expectancy. The clinical features, investigations and
      management of Duchenne muscular dystrophy are reviewed, as well as the latest in
      some of the novel therapies. 

PMID- 25752878
TI  - Reduced risk of relapse after long-term nucleos(t)ide analogue consolidation
      therapy for chronic hepatitis B.
AB  - BACKGROUND: Before stopping nucleos(t)ide analogue (NA) treatment in chronic
      hepatitis B (CHB), 6-12 months of consolidation therapy is recommended. AIM: To
      investigate the effect of consolidation therapy on off-treatment outcomes in CHB
      patients. METHODS: We included 94 patients who stopped NA after at least 1 year
      of therapy. Patients could be HBeAg-positive or HBeAg-negative at start-of
      treatment, but were HBeAg-negative and had undetectable HBV DNA at time of
      discontinuation. Consolidation therapy was defined as treatment after the first
      undetectable HBV DNA (and HBeAg loss for HBeAg-positive patients) until NA
      cessation. RESULTS: At 3 years, 74% of the start-of-treatment HBeAg-positive and
      75% of the start-of-treatment HBeAg-negative patients developed HBV DNA >2000
      IU/mL at a single time point, whereas a persistent virological relapse (>=2 tests
      of HBV DNA >2000 IU/mL 6 months apart within 1 year) developed in 49% of the
      start-of-treatment HBeAg-positive and 53% of the start-of-treatment HBeAg
      negative patients. For both HBeAg-positive and HBeAg-negative patients,
      consolidation therapy of >=3 years was associated with lower persistent
      virological relapse rates compared to <1 year (1-year relapse rate: 25% vs. 54%;
      P = 0.063 and 24% vs. 57%; P = 0.036, respectively). At 3 years, 9% of the HBeAg
      positive and 14% of the HBeAg-negative patients became HBsAg-negative. Prolonged
      consolidation therapy increased the likelihood of HBsAg loss. Two cirrhotic
      patients developed hepatic decompensation but both recovered. CONCLUSIONS: After
      nucleos(t)ide analogue discontinuation, relapse was common in patients with
      chronic hepatitis B. Prolongation of consolidation therapy beyond 3 years
      decreased the risk of persistent virological relapse and increased the likelihood
      of HBsAg loss.

PMID- 25752879
TI  - Accessibility of trial reports for drugs stalling in development: a systematic
      assessment of registered trials.
AB  - OBJECTIVE: To quantify the proportion of trials for unsuccessfully licensed drugs
      that are not published. DESIGN: A systematic assessment of the availability of
      published research reports for publicly registered trials testing drugs stalling
      in clinical development ("stalled drugs") and drugs receiving regulatory
      licensure in the same time period ("licensed drugs"). DATA SOURCES: Searches of
      clinicaltrials.gov, Google Scholar, PubMed, Embase, and electronic query of
      contacts in registries to identify trials and assess publication status.
      ELIGIBILITY CRITERIA: The cohort of licensed drugs consisted of all disease
      modifying drugs in cancer, cardiovascular disease, or neurological disorders that
      received Food and Drug Administration licensure during 2005 to 2009 inclusive.
      The cohort of stalled drugs included unlicensed drugs in the same disease areas
      that had at least one completed phase III trial before 2009 and no evidence of
      any clinical trial activity after 31 December 2009. Inclusion criteria for
      registered trials advanced into publication searching were an intervention tested
      in a disease modifying, phase II, III, or IV trial registered on
      clinicaltrials.gov, with enrolment of at least one patient, that reported primary
      outcome collection end date between 1 January 2006 and 31 December 2008. RESULTS:
      The unadjusted publication proportion for registered trials of licensed drugs was
      75% (72/96) versus 37% (30/81) for stalled drugs. The adjusted hazard ratio for
      publication was 2.7 (95% confidence interval 1.7 to 4.3) in favour of licensed
      drug trials. Higher publication rates for licensed drug trials were observed
      regardless of disease type, sponsorship, trial phase, and geography. The rate of
      non-publication of stalled drug trials was significantly higher for studies that
      did not complete enrolment compared with licensed drug trials. A total of 20,135
      patients participated in trials of stalled drugs that were never published.
      CONCLUSIONS: Much of the information collected in unsuccessful drug trials is
      inaccessible to the broader research and practice communities. These findings
      provide an evidence base and rationale for policy reforms aimed at promoting
      transparency, ethics, and accountability in clinical research.

PMID- 25752880
TI  - Effects of anesthetic technique on blood loss and complications after
      simultaneous bilateral total knee arthroplasty.
AB  - AIMS: Anesthetic technique affects perioperative outcomes, but less was known in
      simultaneous bilateral total knee arthroplasty (BTKA). A single center,
      retrospective analysis was carried out to prove the hypothesis that utilization
      of regional anesthesia would result in favorable perioperative outcomes. METHODS:
      Medical records of patients admitted for simultaneous BTKA between 2004 and 2013
      were analyzed. Two groups, the general anesthesia (GA) and regional anesthesia
      (RA) group, were identified. Patient preoperative characteristics were compared.
      Perioperative outcomes measured included blood loss, transfusion requirement,
      length of hospitalization, operating time, and 30-day perioperative
      complications. RESULTS: A total of 513 patients were identified, 54.6% were
      performed under GA, and 45.4% under RA. Patient characteristics were similar
      between the two groups, except that patients operated under GA were younger than
      those under RA. RA was associated with significantly less perioperative blood
      loss (981 vs. 1075 mL, p = 0.017) and 30-day complications (6.4 vs. 13.2%, p =
      0.016). Systemic and organ specific infections were particularly lower in the RA
      group (0.4 vs. 3.9%, p = 0.009). Transfusion requirement, length of
      hospitalization, and operating time were similar between the two groups. After
      correcting for covariates, RA offered a 92 mL (p = 0.023) reduction in blood loss
      and 49% less overall complications (p = 0.047), compared to GA. CONCLUSION:
      Patients who underwent simultaneous BTKA under RA had lesser blood loss and lower
      complication rate than GA. The impact of RA can be further exploited to improve
      perioperative outcomes of simultaneous BTKA in addition to various other
      interventions.

PMID- 25752881
TI  - MiR-138/peroxisome proliferator-activated receptor beta signaling regulates human
      hypertrophic scar fibroblast proliferation and movement in vitro.
AB  - Excessive scars affect a patient's quality of life, both physically and
      psychologically, by causing pruritus, pain and contractures. Because there is a
      poor understanding of the complex mechanisms underlying the processes of
      hypertrophic scar formation, most therapeutic approaches remain clinically
      unsatisfactory. In this study, we found that miR-138 was downregulated and
      peroxisome proliferator-activated receptor (PPARbeta) was inversely upregulated
      in hypertrophic scar tissues compared to in paired normal skin tissues. Using a
      dual-luciferase assay, we validated that miR138 directly targets PPARbeta and
      regulates its expression at the transcriptional and translational levels. In gain
      and-loss experiments, we found that miR-138/PPARbeta signaling regulated human
      hypertrophic scar fibroblast proliferation and movement, and affected scarring
      related protein expression, which suggests that miR-138/PPARbeta signaling is
      important for hypertrophic scarring. Thus, our study provides evidence to help
      determine whether miR-138/PPARbeta signaling may be a potential target for
      hypertrophic scarring management. 

PMID- 25752882
TI  - Prophylactic dexamethasone effectively reduces the incidence of pain flare
      following spine stereotactic body radiotherapy (SBRT): a prospective
      observational study.
AB  - PURPOSE: The purpose of this study was to determine the incidence of pain flare
      (PF) in patients receiving spine stereotactic body radiotherapy (SBRT) treated
      with prophylactic oral dexamethasone (DEX) 1 h before and for 4 days following
      SBRT. METHODS: Forty-seven patients were accrued on this prospective
      observational study. The first cohort of 24 patients was treated with 4 mg, while
      a second cohort of 23 patients treated with 8 mg of DEX. The Brief Pain Inventory
      (BPI) was used to score pain and functional interference each day during SBRT and
      for 10 days following. Comparisons between the 4 and 8 mg cohorts, in addition to
      our previously reported steroid naive patients post SBRT (n = 41), were also
      performed. RESULTS: The total incidence of PF was 19 % (9/47). The incidence in
      the 4 and 8 mg cohorts was 25 % (6/24) and 13 % (3/23), respectively, and the
      difference was not statistically significant (p = 0.46). Comparing functional
      interference, the 4 mg cohort had better profile in walking ability (p < 0.005)
      and relationships with others (p < 0.035) compared to the 8 mg cohort. Compared
      to our previously reported steroid naive cohort, prophylactic DEX significantly
      reduced the incidence of PF (68 vs. 19 %, p < 0.0001, respectively), patients had
      lower worst pain scores, and improved general activity interference outcome.
      CONCLUSION: We recommend prophylactic DEX for patients treated with spine SBRT.
      Our current practice is based on the 4 mg protocol primarily due to the improved
      functional interference outcomes. A randomized trial is required to finalize the
      optimal regimen and schedule.

PMID- 25752883
TI  - Malnutrition is associated with worse health-related quality of life in children
      with cancer.
AB  - PURPOSE: Malnutrition in childhood cancer patients has been associated with lower
      health-related quality of life (HRQOL). However, this association has never
      actually been tested. Therefore, we aimed to determine the association between
      nutritional status and HRQOL in children with cancer. METHODS: In 104 children,
      aged 2-18 years and diagnosed with hematological, solid, or brain malignancies,
      nutritional status and HRQOL were assessed at diagnosis and at 3, 6, and 12
      months using the child- and parent-report versions of the PedsQL 4.0 Generic
      scale and the PedsQL 3.0 Cancer Module. Scores on both scales range from 0 to
      100. RESULTS: Undernourished children (body mass index (BMI) or fat-free mass < 
      2 standard deviation score (SDS)) reported significantly lower PedsQL scores
      compared with well-nourished children on the domains physical functioning (
      13.3), social functioning (-7.0), cancer summary scale (-5.9), and nausea (
      14.7). Overnourished children (BMI or fat mass >2 SDS) reported lower scores on
      emotional (-8.0) and cognitive functioning (-9.2) and on the cancer summary scale
      (-6.6), whereas parent-report scores were lower on social functioning (-7.5).
      Weight loss (>0.5 SDS) was associated with lower scores on physical functioning (
      13.9 child-report and -10.7 parent-report), emotional (-7.4) and social
      functioning (-6.0) (child-report), pain (-11.6), and nausea (-7.8) (parent
      report). Parents reported worse social functioning and more pain in children with
      weight gain (>0.5 SDS) compared with children with stable weight status.
      CONCLUSIONS: Undernutrition and weight loss were associated with worse physical
      and social functioning, whereas overnutrition and weight gain affected the
      emotional and social domains of HRQL. Interventions that improve nutritional
      status may contribute to enhanced health outcomes in children with cancer.

PMID- 25752884
TI  - Development and validation of the Lymphedema Symptom and Intensity Survey-Arm.
AB  - PURPOSE: The purpose of this instrument development project was to create a self
      report tool to evaluate arm lymphedema and associated symptoms in breast cancer
      survivors. METHODS: The Lymphedema Symptom Intensity and Distress Survey-Arm
      (LSIDS-A) was developed and tested in three phases: phase 1-literature review and
      expert panel; phase 2-preliminary validation; and phase 3-final validation.
      RESULTS: Phase 1: The most common symptoms experienced by breast cancer survivors
      with lymphedema were identified. A 52-item scale was developed. Phase 2: 128
      community-dwelling breast cancer survivors (64 with lymphedema, 64 without
      lymphedema) completed the LSIDS-A. Feedback from the participants was that the
      format was "clear" and "made sense"; therefore, the response structure was left
      intact. Sixteen items were deleted leaving a 36-item revised instrument. Phase 3:
      Subsequent testing in a total sample of 236 breast cancer survivors with
      lymphedema was undertaken. The Cronbach's alpha reliability values for the
      overall intensity and distress scores were 0.93 and 0.94, respectively. The Kuder
      Richardson values ranged from 0.66 to 0.92. Divergent validity evaluated against
      Marlowe-Crowne Social Desirebility Scale overall was acceptable (intensity, r s =
      0.08; distress, r s  = -0.12). Convergent validity was acceptable as tested with
      multiple instruments (e.g., Functional Assessment of Cancer Therapy-Breast +4,
      overall intensity r s   = -0.44, overall distress r s   = -.48) CONCLUSIONS: The
      30-item LSIDS-A is a valid and reliable instrument that can be used to assess arm
      lymphedema and its associated symptoms.

PMID- 25752885
TI  - Quality-of-life outcomes in patients with gynecologic cancer referred to
      integrative oncology treatment during chemotherapy.
AB  - OBJECTIVE: Integrative oncology incorporates complementary medicine (CM)
      therapies in patients with cancer. We explored the impact of an integrative
      oncology therapeutic regimen on quality-of-life (QOL) outcomes in women with
      gynecological cancer undergoing chemotherapy. PATIENTS AND METHODS: A prospective
      preference study examined patients referred by oncology health care practitioners
      (HCPs) to an integrative physician (IP) consultation and CM treatments. QOL and
      chemotherapy-related toxicities were evaluated using the Edmonton Symptom
      Assessment Scale (ESAS) and Measure Yourself Concerns and Wellbeing (MYCAW)
      questionnaire, at baseline and at a 6-12-week follow-up assessment. Adherence to
      the integrative care (AIC) program was defined as >= 4 CM treatments, with <= 30
      days between each session. RESULTS: Of 128 patients referred by their HCP, 102
      underwent IP consultation and subsequent CM treatments. The main concerns
      expressed by patients were fatigue (79.8%), gastrointestinal symptoms (64.6%),
      pain and neuropathy (54.5 %), and emotional distress (45.5%). Patients in both
      AIC (n = 68) and non-AIC (n = 28) groups shared similar demographic, treatment,
      and cancer-related characteristics. ESAS fatigue scores improved by a mean of
      1.97 points in the AIC group on a scale of 0-10 and worsened by a mean of 0.27
      points in the non-AIC group (p = 0.033). In the AIC group, MYCAW scores improved
      significantly (p < 0.0001) for each of the leading concerns as well as for well
      being, a finding which was not apparent in the non-AIC group. CONCLUSIONS: An IP
      guided CM treatment regimen provided to patients with gynecological cancer during
      chemotherapy may reduce cancer-related fatigue and improve other QOL outcomes.

PMID- 25752886
TI  - Association between caesarean section and childhood obesity: a systematic review
      and meta-analysis.
AB  - Birth by caesarean section has been recently implicated in the aetiology of
      childhood obesity, but studies examining the association have varied with regard
      to their settings, designs, and adjustment for potential confounders. We
      conducted a systematic review and meta-analysis to summarize the available
      evidence and to explore study characteristics as sources of heterogeneity. A
      search of Medline, EMBASE, and Web of Science identified 28 studies. Random
      effects meta-analysis was used to calculate pooled risk ratios (RR) with 95%
      confidence intervals (CI). Caesarean section had a RR of 1.34 (CI 1.18-1.51) for
      obesity in the child compared with vaginal birth. The RR was lower for studies
      that adjusted for maternal pre-pregnancy weight than for studies that did not
      (1.29, CI 1.16-1.44 vs. 1.55, CI 1.11-2.17). Studies that examined multiple early
      life factors reported lower RRs than studies that specifically examined caesarean
      section (1.39, CI 1.23-1.57 vs. 1.23, CI 0.97-1.56). Effect estimates did not
      vary by child's age at obesity assessment, study design or country income.
      Children born by caesarean section are at higher risk of developing obesity in
      childhood. Findings are limited by a moderate heterogeneity among studies and the
      potential for residual confounding and publication bias. 

PMID- 25752887
TI  - An update on the role of omega-3 fatty acids on inflammatory and degenerative
      diseases.
AB  - Inflammation is involved in the pathophysiology of many chronic diseases, such as
      rheumatoid arthritis and neurodegenerative diseases. Several studies have
      evidenced important anti-inflammatory and immunomodulatory properties of omega-3
      long-chain polyunsaturated fatty acids (n-3 LC-PUFAs). This review illustrates
      current knowledge about the efficacy of n-3 LC-PUFAs (eicosapentaenoic acid (EPA)
      and docosahexaenoic acid (DHA), particularly) in preventing and/or treating
      several chronic inflammatory conditions (inflammatory bowel diseases and
      rheumatoid arthritis) as well as their potential benefits on neurodegenerative
      diseases. It is well established that n-3 LC-PUFAs are substrates for synthesis
      of novel series of lipid mediators (e.g., resolvins, protectins, and maresins)
      with potent anti-inflammatory and pro-resolving properties, which have been
      proposed to partly mediate the protective and beneficial actions of n-3 LC-PUFAs.
      Here, we briefly summarize current knowledge from preclinical studies analyzing
      the actions of EPA- and DHA-derived resolvins and protectins on
      pathophysiological models of rheumatoid arthritis, Alzheimer, and irritable bowel
      syndrome. 

PMID- 25752888
TI  - Glutamate NMDA receptor modulators for the treatment of depression: trials and
      tribulations.

PMID- 25752889
TI  - Safety, pharmacodynamics, and pharmacokinetics of multiple oral doses of delta-9
      tetrahydrocannabinol in older persons with dementia.
AB  - RATIONALE: Data on safety, pharmacodynamics, and pharmacokinetics of
      tetrahydrocannabinol (THC) are lacking in dementia patients. METHODS: In this
      randomized, double-blind, placebo-controlled, crossover trial, we evaluated the
      safety, pharmacodynamics, and pharmacokinetics of THC in ten patients with
      dementia (mean age 77.3 +/- 5.6). For 12 weeks, participants randomly received
      oral THC (weeks 1-6, 0.75 mg; weeks 7-12, 1.5 mg) or placebo twice daily for 3
      days, separated by a 4-day washout period. RESULTS: Only 6 of the 98 reported
      adverse events were related to THC. Visual analog scale (VAS) feeling high, VAS
      external perception, body sway-eyes-open, and diastolic blood pressure were not
      significantly different with THC. After the 0.75-mg dose, VAS internal perception
      (0.025 units; 95% CI 0.010-0.040) and heart rate (2 beats/min; 95% CI 0.4-3.8)
      increased significantly. Body sway-eyes-closed increased only after 1.5 mg (0.59
      degrees /s; 95% CI 0.13-1.06). Systolic blood pressure changed significantly
      after both doses of THC (0.75 mg, -7 mmHg, 95% CI -11.4, -3.0; 1.5 mg, 5 mmHg,
      95% CI 1.0-9.2). The median T max was 1-2 h, with THC pharmacokinetics increasing
      linearly with increasing dose, with wide interindividual variability (CV% up to
      140%). The mean C max (ng/mL) after the first dose (0-6 h) was 0.41 (0.18-0.90)
      for the 0.75-mg dose and 1.01 (0.53-1.92) for the 1.5-mg dose. After the second
      dose (6-24 h), the C max was 0.50 (0.27-0.92) and 0.98 (0.46-2.06), respectively.
      CONCLUSIONS: THC was rapidly absorbed and had dose-linear pharmacokinetics with
      considerable interindividual variation. Pharmacodynamic effects, including
      adverse events, were minor. Further studies are warranted to evaluate the
      pharmacodynamics and efficacy of higher THC doses in older persons with dementia.

PMID- 25752890
TI  - Overexpression of Lysophosphatidylcholine Acyltransferase 1 and Concomitant Lipid
      Alterations in Gastric Cancer.
AB  - BACKGROUND: The involvement of lipids in carcinogenic and developmental processes
      has been reported in some malignancies, but their roles in gastric cancer remain
      to be analyzed. In this study, we compared the lipid content of gastric cancer
      tissue and adjacent nonneoplastic mucosa using imaging mass spectrometry.
      METHODS: Mass spectra were acquired from 12 sections of human gastric cancer
      tissue and adjacent nonneoplastic mucosa using a matrix-assisted laser desorption
      ionization time-of-flight tandem mass spectrometry type mass spectrometer
      equipped with a 355 nm Nd:YAG laser. Protein expression of
      lysophosphatidylcholine acyltransferase 1 (LPCAT1), which converts
      lysophosphatidylcholine (LPC) to phosphatidylcholine (PC) in the presence of acyl
      CoA in Lands' cycle, was immunohistochemically analyzed in 182 gastric cancer
      specimens. RESULTS: The averaged mass spectra from the cancer tissue and
      nonneoplastic mucosa were identical. Most of the signals that differed between
      cancer tissue and nonneoplastic mucosa corresponded to phospholipids, the
      majority of which were PC and LPC. Two signals, m/z 798.5 and 496.3, were higher
      and lower, respectively, in cancer tissues, predominantly in differentiated
      adenocarcinoma. A database search enabled identification of the ions at m/z 798.5
      and m/z 496.3 as potassium-adducted PC (16:0/18:1) and proton-adducted LPC
      (16:0), respectively. Immunohistochemical analysis revealed that LPCAT1 was
      highly expressed in cancer lesions compared to nonneoplastic mucosa,
      predominantly in differentiated adenocarcinoma. LPCAT1 expression levels
      correlated positively with tumor differentiation and negatively with tumor depth,
      lymph node metastasis, and tumor stage. CONCLUSIONS: Overexpressed LPCAT1 protein
      in gastric mucosa appears to play important roles in the tumorigenic process of
      gastric cancer by converting LPC to PC.

PMID- 25752891
TI  - Abdominal Infection Suppresses the Number and Activity of Intrahepatic Natural
      Killer Cells and Promotes Tumor Growth in a Murine Liver Metastasis Model.
AB  - BACKGROUND: Increasing evidence suggests that postoperative infection is
      associated with poorer long-term outcome in various malignancies. However, the
      mechanism of poor prognosis induced by postoperative infection has not been
      clearly explained. We sought to determine whether abdominal infection promotes
      cancer metastases in a murine liver metastasis model, and to investigate the role
      of liver natural killer (NK) cells on antitumor immunity during abdominal
      infection. METHODS: Female BALB/c (8-10 weeks old) mice were inoculated with NL
      17 colon cancer cells into the spleen and then subjected to abdominal infection
      induced by cecal ligation and puncture (CLP) or sham treatment. The extent of
      liver metastases and cytokine production in the serum and liver were
      investigated. Cell fraction and cytotoxic activities of liver mononuclear cells
      (MNCs) were elucidated. RESULTS: CLP mice had poorer survival and their serum
      levels of IL-6, -10, and -12p70 were significantly elevated on day 1 compared
      with sham-treated and control mice. No obvious differences in cytokine levels of
      the liver homogenates were identified among the three groups, except IL-12p70
      levels in CLP mice on day 7 significantly decreased. The cytotoxic activities of
      liver MNCs were significantly suppressed in CLP mice soon after tumor
      inoculation. Flow cytometry revealed a decrease in NK cells in the liver and
      perforin and granzyme B expression levels. CONCLUSIONS: Abdominal infection
      promoted liver metastases in a murine liver metastasis model, which may be
      partially caused by a decrease in the number and activity of NK cells during
      abdominal infection.

PMID- 25752892
TI  - Laparoscopic Total Pelvic Exenteration for Locally Recurrent Rectal Cancer.
AB  - BACKGROUND: Extended surgery for locally recurrent rectal cancer is technically
      demanding because of the severe fibrosis around the tumor, which makes it
      difficult to achieve R0 resection. Although laparoscopic total pelvic
      exenteration has been carried out in patients with primary rectal cancer,1 (,) 2
      to our knowledge ours is the first report of this laparoscopic procedure for
      locally recurrent rectal cancer. METHODS: A 70-year-old man who underwent
      laparoscopic low anterior resection for stage II rectal cancer was diagnosed as
      having two separate local recurrences near the anastomotic site. We decided to
      perform laparoscopic total pelvic exenteration after neoadjuvant
      chemoradiotherapy. The branches of the internal iliac vessels were carefully
      identified and divided. Presacral dissection behind the neorectum was carried out
      above the anastomotic site. Ligation of the dorsal vein complex was performed
      under direct visualization, with the patient in the jack-knife position. The
      perineal defect was reconstructed using a bilateral V-Y advancement of the
      musculocutaneous flaps of the gluteus maximus. An ileal conduit was constructed
      extracorporeally via an umbilical incision, after placing the patient in the
      lithotomy position. RESULTS: The total operative time was 18 h and 5 min, with an
      estimated blood loss of 750 mL. Final pathology showed negative resection
      margins. CONCLUSIONS: Laparoscopic total pelvic exenteration for locally
      recurrent rectal cancer is a technically challenging procedure requiring a long
      operative time. However, as demonstrated by this case, it can provide a very
      clear view of the operative field, allowing precise dissection, less blood loss,
      and a smaller abdominal wound.

PMID- 25752893
TI  - A New Statistical Model Identified Two-thirds of Clinical T1 Gastric Cancers as
      Possible Candidates for Endoscopic Treatment.
AB  - BACKGROUND: Clinical T1 gastric cancer has low metastatic potential to lymph
      nodes and is generally curable by local treatment. Endoscopic resection can
      preserve the whole stomach and does not impair the patient's quality of life;
      however, its indication is strictly limited to the subset of patients without
      nodal metastasis. The study was designed to predict reliably the patients without
      nodal metastasis based only on the clinical information. METHODS: We examined
      patients with clinical T1 disease who were treated with surgery. The clinically
      available information was evaluated for its ability to predict nodal metastasis
      by logistic regression model. Then, the predictive ability of the logistic
      regression model using the risk factors for nodal metastasis was evaluated by a
      receiver operating characteristic curve. RESULTS: A total of 511 patients were
      entered into this study. The clinical depth (cT1a or cT1b), maximal tumor
      diameter, and pathological type were confirmed to be significantly different
      between patients with and without nodal metastasis. The cutoff value of the tumor
      diameter differed depending on the histology and clinical depth: 79 mm for
      differentiated type and 48 mm for undifferentiated type in cT1a tumors, and 43 mm
      for differentiated type and 11 mm for undifferentiated type in cT1b tumors.
      According to these criteria, 348 of the 511 patients (68.1 %) were classified to
      have predictive N0 status. The negative predictive value was 95.7 % (95 %
      confidence interval 94.0-97.5 %). CONCLUSIONS: The predictive criteria based on
      the multivariate logistic model identified that almost two-thirds of the patients
      with clinical T1 gastric cancer were possible candidates for endoscopic
      treatment.

PMID- 25752894
TI  - Artificial Intelligence Systems as Prognostic and Predictive Tools in Ovarian
      Cancer.
AB  - BACKGROUND: The ability to provide accurate prognostic and predictive information
      to patients is becoming increasingly important as clinicians enter an era of
      personalized medicine. For a disease as heterogeneous as epithelial ovarian
      cancer, conventional algorithms become too complex for routine clinical use. This
      study therefore investigated the potential for an artificial intelligence model
      to provide this information and compared it with conventional statistical
      approaches. METHODS: The authors created a database comprising 668 cases of
      epithelial ovarian cancer during a 10-year period and collected data routinely
      available in a clinical environment. They also collected survival data for all
      the patients, then constructed an artificial intelligence model capable of
      comparing a variety of algorithms and classifiers alongside conventional
      statistical approaches such as logistic regression. RESULTS: The model was used
      to predict overall survival and demonstrated that an artificial neural network
      (ANN) algorithm was capable of predicting survival with high accuracy (93 %) and
      an area under the curve (AUC) of 0.74 and that this outperformed logistic
      regression. The model also was used to predict the outcome of surgery and again
      showed that ANN could predict outcome (complete/optimal cytoreduction vs.
      suboptimal cytoreduction) with 77 % accuracy and an AUC of 0.73. CONCLUSIONS:
      These data are encouraging and demonstrate that artificial intelligence systems
      may have a role in providing prognostic and predictive data for patients. The
      performance of these systems likely will improve with increasing data set size,
      and this needs further investigation.

PMID- 25752895
TI  - The Impact of Perioperative Red Blood Cell Transfusions on Long-Term Outcomes
      after Hepatectomy for Colorectal Liver Metastases.
AB  - BACKGROUND: Red blood cell transfusions (RBCTs) are associated with cancer
      recurrence following resection of colorectal cancer. Their impact after
      colorectal liver metastases (CRLM) resection remains debated. We sought to
      explore the association between perioperative RBCT and oncologic outcomes
      following resection of CRLM. METHODS: We reviewed patients undergoing partial
      hepatectomy for CRLM from 2003 to 2012 at a single institution. Date of death was
      abstracted from a validated population-based cancer registry. Primary outcome was
      overall survival (OS). Secondary outcome was recurrence-free survival (RFS).
      Survivals were estimated using Kaplan-Meier methods and compared with log-rank
      test based on transfusion status. Cox regression analysis examined the
      association of RBCT with OS and RFS, while adjusting for age, preoperative
      chemotherapy, Clinical Risk Score, and period of treatment (2003-2007 vs. 2008
      2012). RESULTS: Among 483 patients, 27.5 % received RBCT. Ninety-day
      postoperative mortality was 4.8 %. At median follow-up of 33 (interquartile range
      20.1-54.8) months, 5-year OS was inferior in transfused patients (45.9 vs. 61.0
      %; p < 0.0001). Five-year RFS was decreased with RBCT (15.5 vs. 31.6 %; p <
      0.0001). The difference persisted when considering only 90-day survivors for 5
      year OS (53.1 vs. 61.9 %, p = 0.023) and RFS (15.6 vs. 31.6 %; p < 0.0001). After
      adjustment for prognostic factors, RBCT was independently associated with
      decreased OS (hazard ratio 2.24; 95 % confidence interval 1.60-3.15) and RFS
      (hazard ratio 1.71; 95 % confidence interval 1.28-2.28). CONCLUSIONS:
      Perioperative RBCT is independently associated with decreased OS and RFS
      following hepatectomy for CRLM. Interventions to minimize and rationalize the use
      of RBCT for hepatectomy are warranted to mitigate this detrimental effect on long
      term outcomes.

PMID- 25752896
TI  - How Stereotype Threat Affects Healthy Older Adults' Performance on Clinical
      Assessments of Cognitive Decline: The Key Role of Regulatory Fit.
AB  - OBJECTIVES: Stereotype threat can impair older adults' performance on clinical
      assessments for cognitive decline. We examined why this occurs. Based upon the
      regulatory focus account of stereotype threat, we predicted that the effects of
      stereotype threat should depend upon the assessments' reward structure.
      Stereotype threat should be associated with poor performance when the assessment
      emphasizes gaining correct answers, but not when it emphasizes avoiding mistakes.
      METHOD: Healthy older adults completed a series of mental status examinations.
      Half of the participants completed these examinations under stereotype threat
      about their cognitive abilities. Monetary incentives were also manipulated. For
      half of the participants correct responding led to gains. For the remaining
      participants incorrect responding/forgetting led to losses. RESULTS: Consistent
      with the regulatory focus account, stereotype threat was associated with poor
      performance when the mental status examinations had a gains-based structure, but
      not when they had a losses-based structure. DISCUSSION: Older adults respond to
      stereotype threat by becoming vigilant to avoid the losses that will make them
      their worst. Researchers and clinicians can capitalize on this motivational
      change to combat stereotype threat's negative effects. By using a loss-avoidance
      frame, stereotype threat's negative effects can be attenuated or even eliminated.

PMID- 25752897
TI  - Age Differences in Emotional Well-Being Vary by Temporal Recall.
AB  - OBJECTIVE: Older adults often appraise and remember events less negatively than
      younger adults. These tendencies may influence reports that rely more on
      nonexperiential, reconstructive processes. As such, the current study examined
      whether age differences may be more pronounced for reports of emotions that span
      across increasingly longer temporal epochs compared to reports of more proximal
      emotional experiences. METHOD: Participants (aged 25-74 during Burst 1) from the
      Midlife in the United States Survey and the National Study of Daily Experiences
      reported the negative affect they experienced across a month, a week, and
      throughout the day at two measurement bursts 10 years apart. RESULTS: Across all
      negative affect measures, older age was related to lower levels of negative
      affect. The effect of age, however, varied across the three temporal epochs, such
      that age differences were smallest when people reported their daily negative
      affect and greatest when they reported their monthly negative affect. DISCUSSION:
      Taking into account how emotion reports differ based on method provides a more
      realistic picture of emotional experience in adulthood. Findings suggest that age
      differences in emotional experiences vary based on whether questions ask about
      short versus longer time periods. Age advantages are most pronounced when people
      recall emotions across increasingly longer periods of time.

PMID- 25752898
TI  - Early resting myocardial computed tomography perfusion for the detection of acute
      coronary syndrome in patients with coronary artery disease.
AB  - BACKGROUND: Acute rest single-photon emission computed tomography-myocardial
      perfusion imaging (SPECT-MPI) has high predictive value for acute coronary
      syndrome (ACS) in emergency department patients. Prior studies have shown
      excellent agreement between rest/stress computed tomography perfusion (CTP) and
      SPECT-MPI, but the value of resting CTP (rCTP) in acute chest pain triage remains
      unclear. We sought to determine the diagnostic accuracy of early rCTP,
      incremental value beyond obstructive coronary artery disease (CAD; >=50%
      stenosis), and compared early rCTP to late stress SPECT-MPI in patients with CAD
      presenting with suspicion of ACS to the emergency department. METHODS AND
      RESULTS: In this prespecified subanalysis of 183 patients (58.1+/-10.2 years; 33%
      women), we included patients with any CAD by coronary computed tomography
      angiography (CCTA) from Rule Out Myocardial Infarction Using Computer-Assisted
      Tomography I. rCTP was assessed semiquantitatively, blinded to CAD
      interpretation. Overall, 31 had ACS and 48 had abnormal rCTP. Sensitivity and
      specificity of rCTP for ACS were 48% (95% confidence interval [CI], 30%-67%) and
      78% (95% CI, 71%-85%), respectively. rCTP predicted ACS (adjusted odds ratio,
      3.40 [95% CI, 1.37-8.42]; P=0.008) independently of obstructive CAD, and
      sensitivity for ACS increased from 77% (95% CI, 59%-90%) for obstructive CAD to
      90% (95% CI, 74%-98%) with addition of rCTP (P=0.05). In a subgroup undergoing
      late rest/stress SPECT-MPI (n=81), CCTA/rCTP had noninferior discriminatory value
      to CCTA/SPECT-MPI (area under the curve, 0.88 versus 0.90; P=0.64) using a
      noninferiority margin of 10%. CONCLUSIONS: Early rCTP provides incremental value
      beyond obstructive CAD to detect ACS. CCTA/rCTP is noninferior to CCTA/SPECT-MPI
      to discriminate ACS and presents an attractive alternative to triage patients
      presenting with acute chest pain. CLINICAL TRIAL REGISTRATION URL:
      http://www.clinicaltrials.gov. Unique identifier: NCT00990262.

PMID- 25752899
TI  - Lack of association between epicardial fat volume and extent of coronary artery
      calcification, severity of coronary artery disease, or presence of myocardial
      perfusion abnormalities in a diverse, symptomatic patient population: results
      from the CORE320 multicenter study.
AB  - BACKGROUND: Epicardial fat may play a role in the pathogenesis of coronary artery
      disease (CAD). We explored the relationship of epicardial fat volume (EFV) with
      the presence and severity of CAD or myocardial perfusion abnormalities in a
      diverse, symptomatic patient population. METHODS AND RESULTS: Patients (n=380)
      with known or suspected CAD who underwent 320-detector row computed tomographic
      angiography, nuclear stress perfusion imaging, and clinically driven invasive
      coronary angiography for the CORE320 international study were included. EFV was
      defined as adipose tissue within the pericardial borders as assessed by computed
      tomography using semiautomatic software. We used linear and logistic regression
      models to assess the relationship of EFV with coronary calcium score, stenosis
      severity by quantitative coronary angiography, and myocardial perfusion
      abnormalities by single photon emission computed tomography (SPECT). Median EFV
      among patients (median age, 62.6 years) was 102 cm(3) (interquartile range: 53).
      A coronary calcium score of >=1 was present in 83% of patients. Fifty-nine
      percent of patients had >=1 coronary artery stenosis of >=50% by quantitative
      coronary angiography, and 49% had abnormal myocardial perfusion results by SPECT.
      There were no significant associations between EFV and coronary artery calcium
      scanning, presence severity of >=50% stenosis by quantitative coronary
      angiography, or abnormal myocardial perfusion by SPECT. CONCLUSIONS: In a diverse
      population of symptomatic patients referred for invasive coronary angiography, we
      did not find associations of EFV with the presence and severity of CAD or with
      myocardial perfusion abnormalities. The clinical significance of quantifying EFV
      remains uncertain but may relate to the pathophysiology of acute coronary events
      rather than the presence of atherosclerotic disease.

PMID- 25752901
TI  - Growth arrest-specific 6 and cardiometabolic risk factors in patients with
      psoriasis.
AB  - OBJECTIVES: An increased risk for cardiovascular disease with psoriasis has been
      reported. Growth Arrest-Specific 6 (GAS6) amplifies pro-inflammatory endothelial
      cell activation via TAM receptors. However, it also inhibits inflammation by
      multiple mechanisms including phagocytosis. The objective of this study was to
      investigate whether plasma GAS6 levels are associated with conventional
      cardiometabolic (CM) risk factors in patients with psoriasis. METHODS: Forty
      patients diagnosed with psoriasis (22 male, mean age: 43.3 +/- 13.8 years) and 40
      age-/sex-matched healthy controls (22 male, mean age: 39.3 +/- 8.9 years) were
      included in the study. CM risk factors (hypertension, hyperlipidemia, diabetes
      mellitus, and cigarette smoking) were identified. GAS6 levels were measured by
      ELISA. RESULTS: There were no significant differences between the plasma GAS6
      levels of patients with psoriasis compared to the control group (6.6 +/- 2.0
      ng/mL, 7.6 +/- 2.8 ng/mL, respectively, P > 0.05). However, GAS6 levels of
      patients with psoriasis having a smoking history (n = 11) were significantly
      lower than both patients with psoriasis who had no smoking history (n = 29) and
      controls (5.5 +/- 1.7 ng/mL, 6.9 +/- 1.9 ng/mL, 7.6 +/- 2.8 ng/mL, respectively,
      P < 0.05). Similarly, psoriasis patients with at least one CM risk factor showed
      lower GAS6 levels compared to subjects without any CM risk factor (5.7 +/- 1.7
      ng/mL, 7.3 +/- 2.0 ng/mL, P < 0.01). There was no correlation between the GAS6
      level, disease duration or PASI score (r = 0.150, -0.150, and P = 0.310, 0.398,
      respectively). CONCLUSIONS: This pilot study provides the first evidence in
      humans for an association between low plasma GAS6 levels and conventional risk
      factors in psoriasis. Further large scale, prospective studies are needed to
      confirm these results.

PMID- 25752900
TI  - High expression of CD26 accurately identifies human bacteria-reactive MR1
      restricted MAIT cells.
AB  - Mucosa-associated invariant T (MAIT) cells express the semi-invariant T-cell
      receptor TRAV1-2 and detect a range of bacteria and fungi through the MHC-like
      molecule MR1. However, knowledge of the function and phenotype of bacteria
      reactive MR1-restricted TRAV1-2(+) MAIT cells from human blood is limited. We
      broadly characterized the function of MR1-restricted MAIT cells in response to
      bacteria-infected targets and defined a phenotypic panel to identify these cells
      in the circulation. We demonstrated that bacteria-reactive MR1-restricted T cells
      shared effector functions of cytolytic effector CD8(+) T cells. By analysing an
      extensive panel of phenotypic markers, we determined that CD26 and CD161 were
      most strongly associated with these T cells. Using FACS to sort phenotypically
      defined CD8(+) subsets we demonstrated that high expression of CD26 on CD8(+) 
      TRAV1-2(+) cells identified with high specificity and sensitivity, bacteria
      reactive MR1-restricted T cells from human blood. CD161(hi) was also specific for
      but lacked sensitivity in identifying all bacteria-reactive MR1-restricted T
      cells, some of which were CD161(dim) . Using cell surface expression of CD8,
      TRAV1-2, and CD26(hi) in the absence of stimulation we confirm that bacteria
      reactive T cells are lacking in the blood of individuals with active tuberculosis
      and are restored in the blood of individuals undergoing treatment for
      tuberculosis. 

PMID- 25752903
TI  - Plasma concentrations of levobupivacaine associated with two different
      intermittent wound infusion regimens following surgical ductus ligation in
      preterm infants.
AB  - BACKGROUND: Administration of local anesthetics by a surgically placed wound
      catheter has recently been shown to reduce the need for postoperative morphine
      administration in extremely preterm infants undergoing ductus ligation. The
      primary aim of this randomized safety study was to define the plasma levels of
      levobupivacaine (LB) following two different intermittent infusion regimens.
      METHODS: Eighteen preterm infants 23-27 gestational weeks, median birthweight 721
      g scheduled for ductus ligation were included in the study. All patients were
      anesthetized according to a standardized protocol based on high-dose fentanyl (25
      50 MUg.kg(-1) ). Before skin closure, a subcutaneous catheter was inserted into
      the wound. The patients were randomized to receive one of the two intermittent
      infusion regimens: Group BII: Initial bolus plus early start of the intermittent
      infusion or Group DII: No bolus plus delayed start (8 h) of the intermittent
      infusion. Blood samples for determination of LB plasma concentrations were
      obtained on six occasions during the 24-h postoperative observation period, as
      well as hourly postoperative pain assessments using the Echelle Douleur Inconfort
      Noveau (EDIN) pain scale. RESULTS: Plasma concentrations of LB ranged from 0.094
      to 1.682 MUg.ml(-1) and 0 to 0.549 MUg.ml(-1) in group BII and DII, respectively.
      Both regimens were associated with low postoperative EDIN pain scores (24 h
      median of 0 and 1 in group BII and DII, respectively). No signs of systemic local
      anesthetic toxicity were noted. CONCLUSIONS: The two studied intermittent
      infusion regimens were associated with plasma levels below potentially toxic
      levels and were both associated with adequate postoperative pain scores.

PMID- 25752902
TI  - Washing stored red blood cells in an albumin solution improves their morphologic
      and hemorheologic properties.
AB  - BACKGROUND: Prolonged storage of red blood cells (RBCs) leads to storage lesions,
      which may impair clinical outcomes after transfusion. A hallmark of storage
      lesions is progressive echinocytic shape transformation, which can be partially
      reversed by washing in albumin solutions. Here we have investigated the impact of
      this shape recovery on biorheologic variables. STUDY DESIGN AND METHODS: RBCs
      stored hypothermically for 6 to 7 weeks were washed in a 1% human serum albumin
      (HSA) solution. RBC deformability was measured with osmotic gradient
      ektacytometry. The viscosity of RBC suspensions was measured with a Couette-type
      viscometer. The flow behavior of RBCs suspended at 40% hematocrit was tested with
      an artificial microvascular network (AMVN). RESULTS: Washing in 1% albumin
      reduced higher degrees of echinocytes and increased the frequency of discocytes,
      thereby shifting the morphologic index toward discocytosis. Washing also reduced
      RBC swelling. This shape recovery was not seen after washing in saline, buffer,
      or plasma. RBC shape normalization did not improve cell deformability measured by
      ektacytometry, but it tended to decrease suspension viscosities at low shear
      rates and improved the perfusion of an AMVN. CONCLUSIONS: Washing of stored RBCs
      in a 1% HSA solution specifically reduces echinocytosis, and this shape recovery
      has a beneficial effect on microvascular perfusion in vitro. Washing in 1%
      albumin may represent a new approach to improving the quality of stored RBCs and
      thus potentially reducing the likelihood of adverse clinical outcomes associated
      with transfusion of blood stored for longer periods of time.

PMID- 25752904
TI  - The neural correlates of justified and unjustified killing: an fMRI study.
AB  - Despite moral prohibitions on hurting other humans, some social contexts allow
      for harmful actions such as killing of others. One example is warfare, where
      killing enemy soldiers is seen as morally justified. Yet, the neural
      underpinnings distinguishing between justified and unjustified killing are
      largely unknown. To improve understanding of the neural processes involved in
      justified and unjustified killing, participants had to imagine being the
      perpetrator whilst watching 'first-person perspective' animated videos where they
      shot enemy soldiers ('justified violence') and innocent civilians ('unjustified
      violence'). When participants imagined themselves shooting civilians compared
      with soldiers, greater activation was found in the lateral orbitofrontal cortex
      (OFC). Regression analysis revealed that the more guilt participants felt about
      shooting civilians, the greater the response in the lateral OFC. Effective
      connectivity analyses further revealed an increased coupling between lateral OFC
      and the temporoparietal junction (TPJ) when shooting civilians. The results show
      that the neural mechanisms typically implicated with harming others, such as the
      OFC, become less active when the violence against a particular group is seen as
      justified. This study therefore provides unique insight into how normal
      individuals can become aggressors in specific situations. 

PMID- 25752906
TI  - Impact of computerized physician order entry alerts on prescribing in older
      patients.
AB  - BACKGROUND: A computerized physician order entry (CPOE) system provides
      opportunity for real-time alerts to prescribers. Winthrop University Hospital
      began using CPOE in 2009. OBJECTIVE: We sought to improve prescribing among older
      hospitalized patients by adding alerts to the CPOE system for potentially
      inappropriate medications. METHODS: In January 2011, informational alerts were
      integrated into the CPOE system for selected high-risk medications:
      diphenhydramine, metoclopramide, and all antipsychotics. We evaluated the effect
      of these alerts on prescribing frequency by comparing the number of prescriptions
      during the second quarters of 2010 ("pre-alert") with the second quarters of 2011
      through 2013 ("post-alert"). Prescribing patterns were evaluated through a
      pharmacy database of medication orders. Frequency of prescribing was adjusted for
      total discharges. A comparison was made to ages 18-64 years, and comparing "as
      needed" vs standing orders. RESULTS: In the 65 years of age and older group,
      there were significant reductions in prescription rates pre-alert vs post-alert
      for diphenhydramine (p < 0.001) and metoclopramide (p < 0.001). There was no
      decrease in prescription rates for antipsychotics in older patients (p = 0.80).
      In the younger comparison group, no decreases in prescription rates for those
      drugs were observed. Our analysis is based on numbers of written prescriptions
      and not actual doses administered; therefore, no conclusions concerning the
      effect of these alerts on communication or documentation of risk/benefits of
      these medications can be ascertained. CONCLUSION: The data suggest that
      prescribing rates for drugs with the least efficacy and potential for harm and
      with alternative agents (i.e., diphenhydramine and metoclopramide) can be
      modified by CPOE alerts for older patients.

PMID- 25752905
TI  - Diminished social reward anticipation in the broad autism phenotype as revealed
      by event-related brain potentials.
AB  - Diminished responsivity to reward incentives is a key contributor to the social
      communication problems seen in autism spectrum disorders (ASDs). Social
      motivation theories suggest that individuals with ASD do not experience social
      interactions as rewarding, leading to negative consequences for the development
      of brain circuitry subserving social information. In this study, we examined
      neural responses to social and non-social reward anticipation in 35 typically
      developing young adults, examining modulation of reward sensitivity by level of
      autistic traits. Using an Event-related potential incentive-delay task
      incorporating novel, more ecologically valid forms of reward, higher expression
      of autistic traits was associated with an attenuated P3 response to the
      anticipation of social (simulated real-time video feedback from an observer), but
      not non-social (candy), rewards. Exploratory analyses revealed that this was
      unrelated to mentalizing ability. The P3 component reflects motivated attention
      to reward signals, suggesting attenuated motivation allocation specific to social
      incentives. The study extends prior findings of atypical reward anticipation in
      ASD, demonstrating that attenuated social reward responsiveness extends to
      autistic traits in the range of typical functioning. Results support the
      development of innovative paradigms for investigating social and non-social
      reward responsiveness. Insight into vulnerabilities in reward processing is
      critical for understanding social function in ASD. 

PMID- 25752907
TI  - Adverse effects of topical corticosteroids in paediatric eczema: Australasian
      consensus statement.
AB  - Atopic eczema is a chronic inflammatory disease affecting about 30% of Australian
      and New Zealand children. Severe eczema costs over AUD 6000/year per child in
      direct medical, hospital and treatment costs as well as time off work for
      caregivers and untold distress for the family unit. In addition, it has a
      negative impact on a child's sleep, education, development and self-esteem. The
      treatment of atopic eczema is complex and multifaceted but a core component of
      therapy is to manage the inflammation with topical corticosteroids (TCS). Despite
      this, TCS are often underutilised by many parents due to corticosteroid phobia
      and unfounded concerns about their adverse effects. This has led to extended and
      unnecessary exacerbations of eczema for children. Contrary to popular
      perceptions, (TCS) use in paediatric eczema does not cause atrophy,
      hypopigmentation, hypertrichosis, osteoporosis, purpura or telangiectasia when
      used appropriately as per guidelines. In rare cases, prolonged and excessive use
      of potent TCS has contributed to striae, short-term hypothalamic-pituitary
      adrenal axis alteration and ophthalmological disease. TCS use can also exacerbate
      periorificial rosacea. TCS are very effective treatments for eczema. When they
      are used to treat active eczema and stopped once the active inflammation has
      resolved, adverse effects are minimal. TCS should be the cornerstone treatment of
      atopic eczema in children.

PMID- 25752908
TI  - Neoadjuvant and conversion treatment of patients with colorectal liver
      metastasis: the potential role of bevacizumab and other antiangiogenic agents.
AB  - More than 50 % of patients with colorectal cancer develop liver metastases.
      Surgical resection is the only available treatment that improves survival in
      patients with colorectal liver metastases (CRLM). New antiangiogenic targeted
      therapies, such as bevacizumab, aflibercept, and regorafenib, in combination with
      neoadjuvant and conversion chemotherapy may lead to improved response rates in
      this population of patients and increase the proportion of patients eligible for
      surgical resection. The present review discusses the available data for
      antiangiogenic targeted agents in this setting. One of these therapies,
      bevacizumab, which targets the vascular endothelial growth factor (VEGF) has
      demonstrated good results in this setting. In patients with initially
      unresectable CRLM, the combination of 5-fluorouracil, leucovorin, and oxaliplatin
      (FOLFOX) plus bevacizumab has led to high response and resection rates. This
      combination is also effective for patients with unresectable CRLM. Moreover, the
      addition of bevacizumab to chemotherapy in the neoadjuvant setting of liver
      metastasis has a higher impact on pathological response rate. This drug also has
      a manageable safety profile, and according to recent data, bevacizumab may
      protect against the sinusoidal dilation provoked in the liver by certain
      cytotoxic agents. In phase II trials, antiangiogenic therapy has demonstrated
      benefits in the presurgical treatment of CRLM and may represent a new treatment
      pathway for these patients.

PMID- 25752909
TI  - Molecular structure of an N-formyltransferase from Providencia alcalifaciens O30.
AB  - The existence of N-formylated sugars in the O-antigens of Gram-negative bacteria
      has been known since the middle 1980s, but only recently have the biosynthetic
      pathways for their production been reported. In these pathways, glucose-1
      phosphate is first activated by attachment to a dTMP moiety. This step is
      followed by a dehydration reaction and an amination. The last step in these
      pathways is catalyzed by N-formyltransferases that utilize N(10) 
      formyltetrahydrofolate as the carbon source. Here we describe the three
      dimensional structure of one of these N-formyltransferases, namely VioF from
      Providencia alcalifaciens O30. Specifically, this enzyme catalyzes the conversion
      of dTDP-4-amino-4,6-dideoxyglucose (dTDP-Qui4N) to dTDP-4,6-dideoxy-4-formamido-d
      glucose (dTDP-Qui4NFo). For this analysis, the structure of VioF was solved to
      1.9 A resolution in both its apoform and in complex with tetrahydrofolate and
      dTDP-Qui4N. The crystals used in the investigation belonged to the space group
      R32 and demonstrated reticular merohedral twinning. The overall catalytic core of
      the VioF subunit is characterized by a six stranded mixed beta-sheet flanked on
      one side by three alpha-helices and on the other side by mostly random coil. This
      N-terminal domain is followed by an alpha-helix and a beta-hairpin that form the
      subunit:subunit interface. The active site of the enzyme is shallow and solvent
      exposed. Notably, the pyranosyl moiety of dTDP-Qui4N is positioned into the
      active site by only one hydrogen bond provided by Lys 77. Comparison of the VioF
      model to that of a previously determined N-formyltransferase suggests that
      substrate specificity is determined by interactions between the protein and the
      pyrophosphoryl group of the dTDP-sugar substrate.

PMID- 25752910
TI  - Gene expression modulation in TGF-beta3-mediated rabbit bone marrow stem cells
      using electrospun scaffolds of various stiffness.
AB  - Tissue engineering has recently evolved into a promising approach for annulus
      fibrosus (AF) regeneration. However, selection of an ideal cell source, which can
      be readily differentiated into AF cells of various regions, remains challenging
      because of the heterogeneity of AF tissue. In this study, we set out to explore
      the feasibility of using transforming growth factor-beta3-mediated bone marrow
      stem cells (tBMSCs) for AF tissue engineering. Since the differentiation of stem
      cells significantly relies on the stiffness of substrate, we fabricated
      nanofibrous scaffolds from a series of biodegradable poly(ether carbonate
      urethane)-urea (PECUU) materials whose elastic modulus approximated that of
      native AF tissue. We cultured tBMSCs on PECUU scaffolds and compared their gene
      expression profile to AF-derived stem cells (AFSCs), the newly identified AF
      tissue-specific stem cells. As predicted, the expression of collagen-I in both
      tBMSCs and AFSCs increased with scaffold stiffness, whereas the expression of
      collagen-II and aggrecan genes showed an opposite trend. Interestingly, the
      expression of collagen-I, collagen-II and aggrecan genes in tBMSCs on PECUU
      scaffolds were consistently higher than those in AFSCs regardless of scaffold
      stiffness. In addition, the cell traction forces (CTFs) of both tBMSCs and AFSCs
      gradually decreased with scaffold stiffness, which is similar to the CTF change
      of cells from inner to outer regions of native AF tissue. Together, findings from
      this study indicate that tBMSCs had strong tendency to differentiate into various
      types of AF cells and presented gene expression profiles similar to AFSCs,
      thereby establishing a rationale for the use of tBMSCs in AF tissue engineering. 

PMID- 25752911
TI  - Antipsychotics and mortality: adjusting for mortality risk scores to address
      confounding by terminal illness.
AB  - OBJECTIVES: To determine whether adjustment for prognostic indices specifically
      developed for nursing home (NH) populations affect the magnitude of previously
      observed associations between mortality and conventional and atypical
      antipsychotics. DESIGN: Cohort study. SETTING: A merged data set of Medicaid,
      Medicare, Minimum Data Set (MDS), Online Survey Certification and Reporting
      system, and National Death Index for 2001 to 2005. PARTICIPANTS: Dual-eligible
      individuals aged 65 and older who initiated antipsychotic treatment in a NH
      (N=75,445). MEASUREMENTS: Three mortality risk scores (Mortality Risk Index
      Score, Revised MDS Mortality Risk Index, Advanced Dementia Prognostic Tool) were
      derived for each participant using baseline MDS data, and their performance was
      assessed using c-statistics and goodness-of-fit tests. The effect of adjusting
      for these indices in addition to propensity scores (PSs) on the association
      between antipsychotic medication and mortality was evaluated using Cox models
      with and without adjustment for risk scores. RESULTS: Each risk score showed
      moderate discrimination for 6-month mortality, with c-statistics ranging from
      0.61 to 0.63. There was no evidence of lack of fit. Imbalances in risk scores
      between conventional and atypical antipsychotic users, suggesting potential
      confounding, were much lower within PS deciles than the imbalances in the full
      cohort. Accounting for each score in the Cox model did not change the relative
      risk estimates: 2.24 with PS-only adjustment versus 2.20, 2.20, and 2.22 after
      further adjustment for the three risk scores. CONCLUSION: Although causality
      cannot be proven based on nonrandomized studies, this study adds to the body of
      evidence rejecting explanations other than causality for the greater mortality
      risk associated with conventional antipsychotics than with atypical
      antipsychotics.

PMID- 25752912
TI  - Is the probability of prenatal diagnosis or termination of pregnancy different
      for fetuses with congenital anomalies conceived following assisted reproductive
      techniques? A population-based evaluation of fetuses with congenital heart
      defects.
AB  - OBJECTIVE: To compare the probability of prenatal diagnosis (PND) and termination
      of pregnancy for fetal anomaly (TOPFA) between fetuses conceived by assisted
      reproductive techniques (ART) and spontaneously-conceived fetuses with congenital
      heart defects (CHD). DESIGN: Population-based observational study. SETTING: Paris
      and surrounding suburbs. POPULATION: Fetuses with CHD in the Paris registry of
      congenital malformations and cohort of children with CHD (Epicard). METHODS:
      Comparison of ART-conceived and spontaneously conceived fetuses taking into
      account potential confounders (maternal characteristics, multiplicity and year of
      birth or TOPFA). MAIN OUTCOME MEASURES: Probability and gestational age at PND
      and TOPFA for ART-conceived versus spontaneously conceived fetuses. RESULTS: The
      probability of PND (28.1% versus 34.6%, P = 0.077) and TOPFA (36.2% versus 39.2%,
      P = 0.677) were not statistically different between ART-conceived (n = 171) and
      spontaneously conceived (n = 4620) fetuses. Estimates were similar after
      adjustment for potential confounders. Gestational age at PND tended to be earlier
      for ART fetuses (23.1 versus 24.8 weeks, P = 0.05) but no statistical difference
      was found after adjustment for confounders. Gestational age at TOPFA was
      comparable between ART-conceived and spontaneously conceived fetuses.
      CONCLUSIONS: In our population, ART conception was not significantly associated
      with the probability of PND or TOPFA for CHD. One implication of our results is
      that live births may be adequate for assessing the overall risk of CHD related to
      ART. However, total prevalence, in particular of severe CHD, would not be
      adequately assessed if TOPFA are not included.

PMID- 25752913
TI  - Neuroprotective effects of vildagliptin in rat rotenone Parkinson's disease
      model: role of RAGE-NFkappaB and Nrf2-antioxidant signaling pathways.
AB  - Gliptins have been recently shown to conquer neuronal degeneration in cell
      cultures via modulating glucagon-like peptide (GLP)-1. This peptide produced in
      the gut not only crosses the blood-brain barrier but is also synthesized in the
      brain and acts on GLP-1R exerting central anti-inflammatory and antiapoptotic
      effects, thus impeding neuronal damage. This study investigated the
      antiparkinsonian effect of vildagliptin, a dipeptidyl peptidase (DPP)-4 inhibitor
      in a rat rotenone model targeting mainly the RAGE-NFkappaB/Nrf2-signaling
      pathways, to judge the potential anti-inflammatory/antioxidant effects of the
      drug. Vildagliptin markedly improved the motor performance in the open field and
      rotarod tests, effects that were emphasized by the accompanied reduction in
      striatal dopamine content. It modified the striatal energy level (ADP/ATP)
      associated with partial antagonism of body weight reduction. This incretin
      enhancer suppressed nuclear factor (NF)kappaB and, consequently, the downstream
      inflammatory mediator tumor necrosis factor-alpha. Normalization of receptor for
      advanced glycated end product (RAGE) is a main finding which justifies the anti
      inflammatory effects of vildagliptin, together with hampering striatal inducible
      nitric oxide synthase, intracellular adhesion molecule-1 as well as
      myeloperoxidase. The antioxidant potential of vildagliptin was depicted as
      entailing reduction in thiobarbituric acid-reactive substances and the
      transcriptional factor Nrf-2 level. Vildagliptin guarded against neuronal demise
      through an antiapoptotic effect as reflected by the reduction in the
      mitochondrial matrix component cytochrome c and the key downstream executioner
      caspase-3. In conclusion, vildagliptin is endowed with various neuroprotective
      effects and thus can be a promising candidate for the management of Parkinson's
      disease. In the rat rotenone model of Parkinson's disease (PD), striatal
      RAGE/NFkappaB signaling was up-regulated associated with elevated levels of
      inflammatory, oxidative stress, and apoptotic mediators resulting in dopaminergic
      neurons death and hence motor impairment. Vildagliptin, a dipeptidyl peptidase
      (DPP)-4 inhibitor, blocked the RAGE/NFkappaB cascade exerting a potential
      antiparkinsonian effect. RAGE, receptor for advanced glycation end product;
      NFkappaB, nuclear factor kappaB; TNFalpha, tumor necrosis factor alpha; ICAM,
      intracellular adhesion molecule; iNOS, inducible nitric oxide synthase; MPO,
      myeloperoxidase. 

PMID- 25752915
TI  - Eucalyptus oil: contact allergy and safety.

PMID- 25752914
TI  - Impact of CYP2C19 polymorphism on the pharmacokinetics of nelfinavir in patients
      with pancreatic cancer.
AB  - AIM: This study evaluated the influence of CYP2C19 polymorphisms on the
      pharmacokinetics of nelfinavir and its metabolite M8 in patients with pancreatic
      cancer. METHODS: Nelfinavir was administered orally to patients for over 10 days.
      The plasma concentrations of nelfinavir and M8 were measured by HPLC. The
      genotypes of CYP2C19*1, CYP2C19*2 and CYP2C19*3 were determined by the polymerase
      chain reaction-restriction fragment length polymorphism method. RESULTS:
      Pharmacokinetic profiles of nelfinavir and M8 were characterized by wide
      interindividual variability. The mean Cmax of nelfinavir in CYP2C19*1/*1 patients
      was 3.89 +/- 0.40 (n = 3) and 5.12 +/- 0.41 (n = 30) ug ml(-1) , while that of
      CYP2C19*1/*2 patients was 3.60 (n = 1) and 6.14 +/- 0.31 (n = 5) ug ml(-1) at the
      doses of 625 and 1250 mg nelfinavir twice daily, respectively. For the M8
      metabolite, the mean Cmax of CYP2C19*1/*1 patients was 1.06 +/- 0.06 (n = 3) and
      1.58 +/- 0.27 (n = 30) ug ml(-1) , while those of CYP2C19*1/*2 patients were 1.01
      (n = 1) and 1.23 +/- 0.15 (n = 5) ug ml(-1) at the doses of 625 and 1250 mg
      nelfinavir twice daily, respectively. The area under the plasma concentration
      time curve (AUC(0,12 h)) values of nelfinavir for CYP2C19*1/*1 patients were
      28.90 +/- 1.27 and 38.90 +/- 4.99 ug ml(-1) .h and for CYP2C19*1/*2 patients,
      AUC(0,12 h) was 28.20 (n = 1) and 40.22 +/- 3.17 (n = 5) ug ml(-1) .h at the
      doses of 625 and 1250 mg nelfinavir twice daily, respectively. The Cmax of
      nelfinavir was significantly higher (P <0.05) in CYP2C19*1/*2 patients but there
      was no statistical difference in AUC(0,12 h). CONCLUSION: CYP2C19*1/*2 genotype
      modestly affected the pharmacokinetic profiles of nelfinavir and M8 in patients
      with locally advanced pancreatic cancer.

PMID- 25752916
TI  - Segmental hypomelanosis and hypermelanosis arranged in a checkerboard pattern are
      distinct naevi: flag-like hypomelanotic naevus and flag-like hypermelanotic
      naevus.
AB  - The categorization of congenital hypo- or hyperpigmented skin lesions following a
      segmental pattern has been a long-lasting matter of debate and have been reported
      under various and often incorrect terms. To reassess published hypomelanotic and
      hypermelanotic lesions that did not follow Blaschko lines nor a phylloid pattern
      of mosaicism, we carried out an extensive and critical review of the worldwide
      literature. Seventy-four retrieved cases consisted of lateralized hypomelanotic
      lesions arranged in a flag-like pattern or appearing as large patches of grossly
      oval or angulated shape and sharp, serrated margins. Sometimes lesions harboured
      maculopapular melanocytic naevi or cooccurred with other segmentally arranged
      naevi. A probably non-random association with extracutaneous anomalies was also
      reported on rare occasions. In 70 cases, lateralized hypermelanotic patches were
      arranged in a flag-like pattern that often appeared as large quadrangular
      patches. Sometimes lesions harboured Spitz naevi. Ten cases belonged to
      phacomatosis melanorosea, whereas several others were part of so far
      uncategorized cases of phacomatosis pigmentovascularis. Flag-like hypomelanosis
      is a distinct naevus type, for which the term 'flag-like hypomelanotic naevus' is
      suggested. Its cooccurrence with extracutaneous abnormalities might represent a
      specific syndrome. Flag-like hypermelanosis is a distinct naevus type, for which
      the term 'flag-like hypermelanotic naevus' is suggested. Its co-occurrence with
      naevus roseus defines phacomatosis melanorosea. Flag-like hypermelanotic naevus
      should be distinguished from the checkerboard-like areas of darker skin as
      observed in chimaeras. 

PMID- 25752917
TI  - Involvement of CD16 in antibody-dependent enhancement of porcine reproductive and
      respiratory syndrome virus infection.
AB  - The immunological effect of porcine reproductive and respiratory syndrome disease
      virus (PRRSV) vaccines is thought to be influenced by a variety of host factors,
      in which antibody-dependent enhancement (ADE) of infection is one crucial factor.
      Here, we assessed the mechanism of ADE of PRRSV infection. First, we found that
      subneutralizing serum could induce ADE of PRRSV infection in porcine alveolar
      macrophages (PAMs). Quantitative PCR, Western blotting and flow cytometry
      revealed that CD16 is the most abundant Fcgamma receptor (FcgammaR) expressed on
      the surface of PAMs; thus, the role of CD16 in ADE of PRRSV infection was
      examined in PAMs. By using functional blocking antibodies, we demonstrated that
      CD16 is involved in enhanced virus production in PRRSV-antibody immune complex
      infected PAMs. Because PAMs co-express different FcgammaR isoforms, we evaluated
      the effects of CD16 in FcgammaR-non-bearing cells by transfection. Using these
      engineered cells, we found that CD16 could specifically bind to the PRRSV
      antibody immune complex and subsequently mediate internalization of the virus,
      resulting in the generation of progeny virus. We also showed that efficient
      expression of CD16 required association of the FcR gamma-chain. Together, our
      findings provide significant new insights into PRRSV infection, which can be
      enhanced by CD16-mediated PRRSV-antibody immune complexes. This CD16-mediated ADE
      may induce a shift in PRRSV tropism towards CD16-expressing cells, distributing
      virus to more organs during virus infection. 

PMID- 25752918
TI  - The level of selected coordinative motor abilities of basketball players aged 16
      18.
AB  - AIM: Coordinative abilities play a very important role in sport. Unfortunately,
      researchers do not confine appropriate attention to this issue. Therefore, the
      aim of this study was an attempt at analysing results of the selected
      coordinative motor abilities: kinesthetic differentiation, quick reaction and
      spatial orientation. It was intended to find out whether the results of trials
      determining manifestations of the particular coordinative abilities exhibit any
      mutual relationships. Forasmuch as a static torque is a parameter determining the
      level of force components of the ability of kinaesthetic differentiation, it
      would like to find out whether its maximum level influences the final result.
      METHODS: Research was carried out on 20 young basketball players with the use of
      a torque meter and Fusion Smart Speed System. RESULTS: It was noticed a lack of
      statistically significant relationships between the results of trials assessing
      manifestations of the ability of kinaesthetic differentiation, quick reaction and
      spatial orientation. However, it was noted statistically significant correlation
      between the maximum static torque and the accuracy of releasing a particular
      value of a static torque. CONCLUSION: The accuracy of releasing a particular
      value of a static torque ought to be classified as a comprehensive ability that
      comprises manifestations of strength abilities and kinaesthetic differentiation.
      Presented trials to evaluation manifestations of the selected coordinative
      abilities could be used by coaches during a training process. Coaches should also
      focus on the development of muscle strength of the upper body and upper limbs of
      basketball players.

PMID- 25752919
TI  - Resident-to-Resident Abuse: A Scoping Review.
AB  - Resident-to-resident abuse involves aggression and violence that occurs between
      long-term care (LTC) home residents and can have serious consequences for both
      aggressors and victims. To date, there has been no attempt to systematically
      assess the breadth of the problem in Canada. To address this gap, we undertook a
      scoping review to enhance understanding of resident-to-resident abuse in LTC
      homes. A redacted Canadian data set on resident-to-resident abuse is also
      reported on. Nine electronic literature databases were searched; a total of 784
      abstracts were identified, but only 32 satisfied the inclusion criteria. The
      majority of records (75%) were retrospective case studies, qualitative studies,
      and reviews/commentaries. Of these, only 14 focused exclusively on resident-to
      resident abuse. The redacted Canadian data set suggests resident-to-resident
      abuse makes up approximately one-third of reported abuse cases. Recommendations
      for future research, clinical practice, and policy are provided to raise
      awareness of this phenomenon to help decrease its incidence. 

PMID- 25752920
TI  - Local specific absorption rate in brain tumors at 7 tesla.
AB  - PURPOSE: MR safety at 7 Tesla relies on accurate numerical simulations of
      transmit electromagnetic fields to fully assess local specific absorption rate
      (SAR) safety. Numerical simulations for SAR safety are currently performed using
      models of healthy patients. These simulations might not be useful for estimating
      SAR in patients who have large lesions with potentially abnormal dielectric
      properties, e.g., brain tumors. THEORY AND METHODS: In this study, brain tumor
      patient models are constructed based on scans of four patients with high grade
      brain tumors. Dielectric properties for the modeled tumors are assigned based on
      electrical properties tomography data for the same patients. Simulations were
      performed to determine SAR. RESULTS: Local SAR increases in the tumors by as much
      as 30%. However, the location of the maximum 10-gram averaged SAR typically
      occurs outside of the tumor, and thus does not increase. In the worst case, if
      the tumor model is moved to the location of maximum electric field intensity,
      then we do observe an increase in the estimated peak 10-gram SAR directly related
      to the tumor. CONCLUSION: Peak local SAR estimation made on the results of a
      healthy patient model simulation may underestimate the true peak local SAR in a
      brain tumor patient.

PMID- 25752921
TI  - Ultrafast Excited-State Deactivation of 8-Hydroxy-2'-deoxyguanosine Studied by
      Femtosecond Fluorescence Spectroscopy and Quantum-Chemical Calculations.
AB  - The fluorescence properties of the 8-hydroxy-2'-deoxyguanosine (8-oxo-dG) in
      aqueous solution at pH 6.5 are studied by steady-state spectroscopy and
      femtosecond fluorescence up-conversion and compared with those of 2'-deoxyguanine
      (dG) and 2'-deoxyguanine monophosphate (dGMP). The steady-state fluorescence
      spectrum of 8-oxo-dG is composed of a broad band that peaks at 356 nm and extends
      over the entire visible spectral region, and its fluorescence quantum yield is
      twice that of dG/dGMP. After excitation at 267 nm, the initial fluorescence
      anisotropy at all wavelengths is lower than 0.1, giving evidence of an ultrafast
      internal conversion (<100 fs) between the two lowest excited pipi* states (Lb and
      La). The fluorescence decays of 8-oxo-dG are biexponential with an average
      lifetime of 0.7 +/- 0.1 ps, which is about two times longer than that of dGMP. In
      contrast with dGMP, only a moderate dynamical shift (~1400 vs 10,000 cm(-1)) of
      the fluorescence spectra of 8-oxo-dG is observed on the time scale of a few
      picoseconds without modification of the spectral shape. PCM/TD-DFT calculations,
      employing either the PBE0 or the M052X functionals, provide absorption spectra in
      good agreement with the experimental one and show that the deactivation path is
      similar to that proposed for dGMP, with a fast motion toward an energy plateau,
      where the purine ring keeps an almost planar geometry, followed by decay to S0,
      via out-of-the plane motion of amino substituent.

PMID- 25752922
TI  - Prevalence of and factors associated with prolonged length of stay in older
      hospitalized medical patients.
AB  - AIM: To characterize elderly medical patients and identify factors associated
      with prolonged length of stay. METHODS: The present prospective observational
      study evaluated consecutive patients aged >=65 years admitted in acute geriatric
      and medical wards. A comprehensive assessment including demographic, clinical,
      functional and cognitive variables was carried out. Delayed discharge was defined
      when patients were discharged later than the date they were deemed medically
      ready for discharge by physicians. The analysis was initially carried out on the
      total sample and subsequently according to whether hospital admission had been
      from home, or from intermediate or long-term facilities. RESULTS: Among 1568
      patients (age 81.3 +/- 7.3 years, 712 men), we observed a high prevalence of
      functional dependence, cognitive impairment, chronic immobilization and frailty
      (50%, 25%, 20% and 40%, respectively). Overall, delayed discharge occurred in 442
      cases - resulting in 2637 days of prolonged hospital stay - and was independently
      associated with impairment in activities of daily living, frailty, high
      comorbidity and inappropriate admission. Among patients admitted from home
      (roughly 90% of the sample), delayed discharge occurred in 392 patients, and was
      independently associated with cognitive impairment, functional dependence, low
      severity of comorbidity and inappropriate admission (OR 3.39). Among patients
      admitted from intermediate or long-term facilities, lower cognitive impairment
      and greater severity of functional dependence were independently associated with
      prolonged stay. CONCLUSIONS: Poor health conditions and high prevalence of
      geriatric syndromes are extremely common among older medical inpatients. Delayed
      discharge was mainly observed in patients admitted from home, and associated with
      cognitive impairment (OR 1.12) and functional dependence (OR 1.49).

PMID- 25752925
TI  - Obituary: Irven DeVore 1934-2014.

PMID- 25752923
TI  - Salvage outcomes in patients with first relapse after fludarabine,
      cyclophosphamide, and rituximab for chronic lymphocytic leukemia: the French
      intergroup experience.
AB  - The optimal management of patients with relapsed chronic lymphocytic leukemia
      (CLL) is dictated by the type of prior therapy, duration of prior response,
      presence of genomic aberrations, age, and comorbidities. The patterns of relapses
      and the clinical outcomes of second-line options after fludarabine
      cyclophosphamide-rituximab (FCR) is given as a frontline treatment are currently
      unknown. In this retrospective and non-randomized study, we report the outcomes
      of 132 patients from databases of 14 French CLL study group centers who needed a
      second-line treatment after FCR frontline. Bendamustine + rituximab (BR) was the
      most frequently used second-line regimen, followed by alemtuzumab-based regimens,
      R-CHOP, and FCR. Median progression-free survival (PFS) was 18 months after BR
      with a median overall survival (OS) not reached. We also found that response
      durations of < 36 months and the presence of del(17p) are critical factors that
      contribute to poor overall survival. BR appears to be an effective salvage
      regimen in our series, both in terms of progression-free and overall survival.
      Patients who relapsed less than 36 months after FCR have a poor outcome, not
      significantly different in this study from patients with early relapses less than
      12 or 24 months.

PMID- 25752924
TI  - Activated expression of AtEDT1/HDG11 promotes lateral root formation in
      Arabidopsis mutant edt1 by upregulating jasmonate biosynthesis.
AB  - Root architecture is crucial for plants to absorb water and nutrients. We
      previously reported edt1 (edt1D) mutant with altered root architecture that
      contributes significantly to drought resistance. However, the underlying
      molecular mechanisms are not well understood. Here we report one of the
      mechanisms underlying EDT1/HDG11-conferred altered root architecture. Root
      transcriptome comparison between the wild type and edt1D revealed that the
      upregulated genes involved in jasmonate biosynthesis and signaling pathway were
      enriched in edt1D root, which were confirmed by quantitative RT-PCR. Further
      analysis showed that EDT1/HDG11, as a transcription factor, bound directly to the
      HD binding sites in the promoters of AOS, AOC3, OPR3, and OPCL1, which encode
      four key enzymes in JA biosynthesis. We found that the jasmonic acid level was
      significantly elevated in edt1D root compared with that in the wild type
      subsequently. In addition, more auxin accumulation was observed in the lateral
      root primordium of edt1D compared with that of wild type. Genetic analysis of
      edt1D opcl1 double mutant also showed that HDG11 was partially dependent on JA in
      regulating LR formation. Taken together, overexpression of EDT1/HDG11 increases
      JA level in the root of edt1D by directly upregulating the expressions of several
      genes encoding JA biosynthesis enzymes to activate auxin signaling and promote
      lateral root formation. 

PMID- 25752926
TI  - The microwave heating mechanism of N-(4-methoxybenzyliden)-4-butylaniline in
      liquid crystalline and isotropic phases as determined using in situ microwave
      irradiation NMR spectroscopy.
AB  - Microwave heating effects are widely used in the acceleration of organic,
      polymerization and enzymatic reactions. These effects are primarily caused by the
      local heating induced by microwave irradiation. However, the detailed molecular
      mechanisms associated with microwave heating effects on the chemical reactions
      are not yet well understood. This study investigated the microwave heating effect
      of N-(4-methoxybenzylidene)-4-butylaniline (MBBA) in liquid crystalline and
      isotropic phases using in situ microwave irradiation nuclear magnetic resonance
      (NMR) spectroscopy, by obtaining (1)H NMR spectra of MBBA under microwave
      irradiation. When heated simply using the temperature control unit of the NMR
      instrument, the liquid crystalline MBBA was converted to the isotropic phase
      exactly at its phase transition temperature (Tc) of 41  degrees C. The
      application of microwave irradiation at 130 W for 90 s while maintaining the
      instrument temperature at 20  degrees C generated a small amount of isotropic
      phase within the bulk liquid crystal. The sample temperature of the liquid
      crystalline state obtained during microwave irradiation was estimated to be 35 
      degrees C by assessing the linewidths of the (1)H NMR spectrum. This partial
      transition to the isotropic phase can be attributed to a non-equilibrium local
      heating state induced by the microwave irradiation. The application of microwave
      at 195 W for 5 min to isotropic MBBA while maintaining an instrument temperature
      of 50  degrees C raised the sample temperature to 160  degrees C. In this study,
      the MBBA temperature during microwave irradiation was estimated by measuring the
      temperature dependent chemical shifts of individual protons in the sample, and
      the different protons were found to indicate significantly different temperatures
      in the molecule. These results suggest that microwave heating polarizes bonds in
      polar functional groups, and this effect may partly explain the attendant
      acceleration of organic reactions. 

PMID- 25752927
TI  - A new indole-alkaloid and a new phenolic-glycoside with cytotoxic activity from
      Strychnos fendleri.
AB  - A new indole alkaloid strychnosinol (1) and a new phenolic-glycoside (2) were
      isolated from the bark and leaves of Strychnos fendleri Sprague & Sandwith,
      together with six known compounds reported for the first time in this species.
      The structures of these compounds were determined on the basis of spectroscopic
      data; mainly those obtained by using (1)H and (13)C NMR (1D and 2D) and mass
      spectrometry. Strychnosinol (1) and the phenolic glycoside (2) together with
      compounds 3-8 were evaluated for cytotoxicity against a panel of five tumour cell
      lines; IC50 values between 0.090 and 0.227 MUM for the human tumour cell lines
      were observed for compound 2.

PMID- 25752928
TI  - Modified lymph vessel flap transplantation for the treatment of refractory
      lymphedema: A case report.
AB  - Lymph vessel flap transplantation (LFT), lymphaticovenous anastomosis (LVA), or
      lymph node flap transfer are sometimes used to treat lymphedema that is resistant
      to conservative treatment. LFT harvested from the contralateral limb has been
      reported for the treatment of lymphedema. Here we report the use of modified LFT
      from the abdominal wall for the treatment of refractory lymphedema. Our patient
      was a 57-year-old patient with secondary lower limb lymphedema was previously
      treated with conservative therapy and lymphaticovenous anastomosis. We first
      examined the lymphatic function of the lower abdominal region in the patient
      using indocyanine green (ICG) lymphography. After confirming the good lymphatic
      function in the right abdominal region, we harvested the pedicled abdominal
      adiposal flap containing multiple abdominal lymph vessels and transferred it to
      the left groin region. The flap (20 * 10 cm2 ) was based on the superficial
      circumflex iliac artery perforator. We anastomosed one lymph vessel in the flap
      to that in the recipient site. We also performed multiple fibrotripsy using a 3
      mm-diameter stainless steel stick inserted into small incisions. The
      postoperative course was uneventful. The circumference measurement was decreased
      by 2.2-13.5 cm at 1 year after the operation. The lower abdominal region has many
      lymph vessel networks and is thought to be a less risky donor site in patients
      with lymphedema than the lower limbs. Thus, LFT may be an option for the
      treatment of chronic lymphedema. (c) 2015 Wiley Periodicals, Inc. Microsurgery
      36:695-699, 2016.

PMID- 25752929
TI  - Ru(II), Os(II), and Ir(III) complexes with chelating pyridyl-mesoionic carbene
      ligands: structural characterization and applications in transfer hydrogenation
      catalysis.
AB  - Chelating ligands with one pyridine donor and one mesoionic carbene donor are
      fast establishing themselves as privileged ligands in homogeneous catalysis. The
      synthesis of several new Ir(III)-Cp*- and Os(II)-Cym complexes (Cp* =
      pentamethylcyclopentadienyl, Cym = p-cymene=4-isopropyl-toluene) derived from
      chelating pyridyltriazolylidenes where the additional pyridine donor was
      incorporated via the azide part of the triazole is presented. Furthermore,
      different 4-substituted phenylacetylene building blocks have been used to
      introduce electronic fine-tuning in the ligands. The ligands thus can be
      generally described as 4-(4-R-phenyl)-3-methyl-1-(pyridin-2-yl)-1H-1,2,3-triazol
      5-ylidene (with R being H (L(1)), Me (L(2)), OMe (L(3)), CN (L(4)), CF3 (L(5)),
      Br (L(6)) or NO2 (L(7))). The corresponding complexes (Ir-1 to Ir-7 and Os-1 to
      Os-7) were characterized by standard spectroscopic methods, and the expected
      three-legged, piano-stool type coordination was unambiguously confirmed by X-ray
      diffraction analysis of selected compounds. Together with Ru(II) analogues
      previously reported by us, a total of 21 complexes were tested as (pre)catalysts
      for the transfer hydrogenation of carbonyl groups, showing a remarkable
      reactivity even at very low catalyst loadings. The electronic effects of the
      ligands as well as different substrates were investigated. Some mechanistic
      elucidations are also presented.

PMID- 25752931
TI  - The effects of interventions to increase exercise adherence in people with
      arthritis: a systematic review.

PMID- 25752933
TI  - Nicotinic Acetylcholine Receptors Mediate the Suppressive Effect of an Injection
      of Diluted Bee Venom into the GV3 Acupoint on Oxaliplatin-Induced Neuropathic
      Cold Allodynia in Rats.
AB  - Oxaliplatin, a platinum-based chemotherapy drug, often induces acute neuropathic
      pain, especially cold allodynia, even after a single administration. Subcutaneous
      injection of diluted bee venom (BV) into acupoints has been used to treat various
      pain symptoms in traditional oriental medicine. Although we previously
      demonstrated the suppressive effect of BV injection on oxaliplatin-induced cold
      allodynia in rats, its neurochemical mechanism remained unclear. This study
      investigates whether and how the cholinergic system mediates the relieving effect
      of BV injection on cold allodynia in oxaliplatin-administered rats. The
      behavioral signs of cold allodynia induced by an oxaliplatin administration (6
      mg/kg, intraperitoneally (i.p.)) were evaluated by a tail immersion test in cold
      water (4 degrees C). BV (0.25 mg/kg, subcutaneously (s.c.)) injection into the
      Yaoyangguan acupoint, located between the spinous processes of the fourth and
      fifth lumbar vertebrae, significantly alleviated the cold allodynia. This
      relieving effect of BV injection on oxaliplatin-induced cold allodynia was
      blocked by a pretreatment with mecamylamine (a non-selective nicotinic receptor
      antagonist, 2 mg/kg, i.p.), but not by atropine (a non-selective muscarinic
      receptor antagonist, 1 mg/kg, i.p.). Further, dihydro-beta
      erythroidinehydrobromide (DHbetaE, an alpha4beta2 nicotinic antagonist, 5 mg/kg,
      i.p.) prevented the anti-allodynic effect of BV, whereas methyllycaconitine (an
      alpha7 nicotinic antagonist, 6 mg/kg, i.p.) did not. Finally, intrathecal
      administration of DHbetaE (10 nM) blocked the BV-induced anti-allodynic effect.
      These results suggest that nicotinic acetylcholine receptors, especially spinal
      alpha4beta2 receptors, but not muscarinic receptors, mediate the suppressive
      effect of BV injection on oxaliplatin-induced acute cold allodynia in rats. 

PMID- 25752934
TI  - Nitrous oxide fluxes in estuarine environments: response to global change.
AB  - Nitrous oxide is a powerful, long-lived greenhouse gas, but we know little about
      the role of estuarine areas in the global N2 O budget. This review summarizes 56
      studies of N2 O fluxes and associated biogeochemical controlling factors in
      estuarine open waters, salt marshes, mangroves, and intertidal sediments. The
      majority of in situ N2 O production occurs as a result of sediment
      denitrification, although the water column contributes N2 O through nitrification
      in suspended particles. The most important factors controlling N2 O fluxes seem
      to be dissolved inorganic nitrogen (DIN) and oxygen availability, which in turn
      are affected by tidal cycles, groundwater inputs, and macrophyte density. The
      heterogeneity of coastal environments leads to a high variability in
      observations, but on average estuarine open water, intertidal and vegetated
      environments are sites of a small positive N2 O flux to the atmosphere (range
      0.15-0.91; median 0.31; Tg N2 O-N yr(-1) ). Global changes in macrophyte
      distribution and anthropogenic nitrogen loading are expected to increase N2 O
      emissions from estuaries. We estimate that a doubling of current median NO3 (-)
      concentrations would increase the global estuary water-air N2 O flux by about
      0.45 Tg N2 O-N yr(-1) or about 190%. A loss of 50% of mangrove habitat, being
      converted to unvegetated intertidal area, would result in a net decrease in N2 O
      emissions of 0.002 Tg N2 O-N yr(-1) . In contrast, conversion of 50% of salt
      marsh to unvegetated area would result in a net increase of 0.001 Tg N2 O-N yr(
      1) . Decreased oxygen concentrations may inhibit production of N2 O by
      nitrification; however, sediment denitrification and the associated ratio of N2
      O:N2 is expected to increase.

PMID- 25752935
TI  - Leptin Modulates Mitochondrial Function, Dynamics and Biogenesis in MCF-7 Cells.
AB  - The adipokine leptin, known for its key role in the control of energy metabolism,
      has been shown to be involved in both normal and tumoral mammary growth. One of
      the hallmarks of cancer is an alteration of tumor metabolism since cancerous
      cells must rewire metabolism to satisfy the demands of growth and proliferation.
      Considering the sensibility of breast cancer cells to leptin, the objective of
      this study was to explore the effects of this adipokine on their metabolism. To
      this aim, we treated the MCF-7 breast cancer cell line with 50 ng/mL leptin and
      analyzed several features related to cellular and mitochondrial metabolism. As a
      result, leptin increased cell proliferation, shifted ATP production from
      glycolysis to mitochondria and decreased the levels of the glycolytic end-product
      lactate. We observed an improvement in ADP-dependent oxygen consumption and an
      amelioration of oxidative stress without changes in total mitochondrial mass or
      specific oxidative phosphorylation (OXPHOS) complexes. Furthermore, RT-PCR and
      western blot showed an up-regulation for genes and proteins related to biogenesis
      and mitochondrial dynamics. This expression signature, together with an increased
      mitophagy observed by confocal microscopy suggests that leptin may improve
      mitochondrial quality and function. Taken together, our results propose that
      leptin may improve bioenergetic efficiency by avoiding the production of reactive
      oxygen species (ROS) and conferring benefits for growth and survival of MCF-7
      breast cancer cells.

PMID- 25752936
TI  - Test-retest reliability of cerebral blood flow and blood oxygenation level
      dependent responses to hypercapnia and hyperoxia using dual-echo pseudo
      continuous arterial spin labeling and step changes in the fractional composition
      of inspired gases.
AB  - PURPOSE: To assess the reproducibility of blood oxygenation level-dependent /
      cerebral blood flow (BOLD/CBF) responses to hypercapnia/hyperoxia using dual-echo
      pseudo-continuous arterial spin labeling (pCASL) and step changes in inspired
      doses. MATERIALS AND METHODS: Eight subjects were scanned twice, within 24 hours,
      using the same respiratory manipulation and imaging protocol. Imaging comprised a
      5-minute anatomical acquisition, allowing segmentation of the gray matter (GM)
      tissue for further analysis, and an 18-minute pCASL functional scan.
      Hypercapnia/hyperoxia were induced by increasing the fraction of inspired CO2 to
      5% and inspired O2 to 60%, alternately. Reproducibility of BOLD and CBF pCASL
      measures was assessed by computing the inter-session coefficient of variation
      (CV) of the respective signals in GM. RESULTS: BOLD and CBF measures in GM were
      robust and consistent, yielding CV values below 10% for BOLD
      hypercapnic/hyperoxic responses (which averaged 1.9 +/- 0.1% and 1.14 +/- 0.02%)
      and below 20% for the CBF hypercapnic response (which averaged 35 +/- 2
      mL/min/100g). The CV for resting CBF was 3.5%. CONCLUSION: It is possible to
      attain reproducible measures of the simultaneous BOLD and CBF responses to blood
      gases, within a reasonable scan time and with whole brain coverage, using a
      simple respiratory manipulation and dual-echo pCASL.

PMID- 25752938
TI  - Cephalosporin use in penicillin-allergic patients: a survey of otolaryngologists
      and literature review.
AB  - OBJECTIVES/HYPOTHESIS: This study investigated the differences between the
      standard guidelines and the practice patterns of otolaryngologists in managing
      "penicillin-allergic" patients. A major goal was to identify factors influencing
      an otolaryngologist's choice of antibiotic. STUDY DESIGN: Cross-sectional survey.
      METHODS: Four hundred seventy members of the American Society of Pediatric
      Otolaryngologists (ASPO) and 150 general otolaryngologists from the Florida
      Society of Otolaryngology (FSO) were surveyed. RESULTS: Ninety-six ASPO members
      (20.4%) and 22 members of FSO (14.6%) responded. When asked about the management
      of a pediatric patient with acute otitis media and a history of a nonsevere
      immunoglobulin E (IgE)-mediated amoxicillin allergy, 54% of ASPO respondents
      indicated they would initiate guideline-recommended cefdinir, whereas only 27% of
      FSO respondents chose cefdinir (P = .02). Otolaryngologists who are fellowship
      trained in pediatrics or have pediatric-focused practices were significantly more
      likely to prescribe cefdinir. Overall, 57% of respondents indicated that they
      were familiar with the literature regarding the cross-reactivity of beta-lactams,
      but only 25% of respondents felt that they could easily differentiate a
      potentially life-threatening IgE-mediated allergy from a non-IgE-mediated drug
      intolerance. CONCLUSIONS: The data show differences between the current
      recommendations and the behavior of otolaryngologists. Pediatric
      otolaryngologists were more familiar with the guideline-recommended therapy,
      likely from their frequent exposure to patients requiring a beta-lactam.
      Nevertheless, most otolaryngologists could benefit from increased awareness of
      the current literature. Patients may be receiving less than optimal medication
      management due to a misidentification of those at risk of life- threatening
      allergic cross-reactions. LEVEL OF EVIDENCE: NA

PMID- 25752937
TI  - Concise Review: Using Stem Cells to Prevent the Progression of Myopia-A Concept.
AB  - The prevalence of myopia has increased in modern society due to the educational
      load of children. This condition is growing rapidly, especially in Asian
      countries where it has already reached a pandemic level. Typically, the younger
      the child's age at the onset of myopia, the more rapidly the condition will
      progress and the greater the likelihood that it will develop the known sight
      threatening complications of high myopia. This rise in incidence of severe myopia
      has contributed to an increased frequency of eye diseases in adulthood, which
      often complicate therapeutic procedures. Currently, no treatment is available to
      prevent myopia progression. Stem cell therapy can potentially address two
      components of myopia. Regardless of the exact etiology, myopia is always
      associated with scleral weakness. In this context, a strategy aimed at scleral
      reinforcement by transplanting connective tissue-supportive mesenchymal stem
      cells is an attractive approach that could yield effective and universal therapy.
      Sunlight exposure appears to have a protective effect against myopia. It is
      postulated that this effect is mediated via local ocular production of dopamine.
      With a variety of dopamine-producing cells already available for the treatment of
      Parkinson's disease, stem cells engineered for dopamine production could be used
      for the treatment of myopia. In this review, we further explore these concepts
      and present evidence from the literature to support the use of stem cell therapy
      for the treatment of myopia.

PMID- 25752939
TI  - Transfusion Medicine in Sub-Saharan Africa: Conference Summary.
AB  - In November 2014, a 3-day conference devoted to transfusion medicine in sub
      Saharan Africa was held in Kampala, Uganda. Faculty from academic institutions in
      Uganda provided a broad overview of issues pertinent to transfusion medicine in
      Africa. The conference consisted of lectures, demonstrations, and discussions
      followed by 5 small group workshops held at the Uganda Blood Transfusion Service
      Laboratories, the Ugandan Cancer Institute, and the Mulago National Referral
      Hospital. Highlighted topics included the challenges posed by increasing clinical
      demands for blood, the need for better patient identification at the time of
      transfusion, inadequate application of the antiglobulin reagent during
      pretransfusion testing, concern regarding proper recognition and evaluation of
      transfusion reactions, the expanded role for nurse leadership as a means to
      improve patient outcomes, and the need for an epidemiologic map of blood usage in
      Africa. Specialty areas of focus included the potential for broader application
      of transcranial Doppler and hydroxyurea therapy in sickle cell disease, African
      specific guidelines for transfusion support of cancer patients, the challenges of
      transfusion support in trauma, and the importance of African-centered clinical
      research in pediatric and obstetric transfusion medicine. The course concluded by
      summarizing the benefits derived from an organized quality program that extended
      from the donor to the recipient. As an educational tool, the slide-audio
      presentation of the lectures will be made freely available at the International
      Society of Blood Transfusion Academy Web site: http://www.isbtweb.org/academy/. 

PMID- 25752940
TI  - Screening Approach for Chiral Separation of beta-Aminoketones by HPLC on Various
      Polysaccharide-Based Chiral Stationary Phases.
AB  - Nine beta-aminoketones were synthesized via Mannich reaction when benzaldehyde
      was condensed with some primary amines and acetophenone. The purified compounds
      were identified by using spectroscopic methods. The enantiomeric separation of
      these derivatives was carried out by high-performance liquid chromatography
      (HPLC) using several coated and immobilized polysaccharide stationary phases,
      namely, Chiralcel((r)) OD-H, Chiralcel((r)) OD, Chiralcel((r)) OJ, Chiralpak((r))
      AD, Chiralpak((r)) IA, and Chiralpak((r)) IB using different mobile phases
      composed of n-hexane and alcohol mixed in various ratios or pure ethanol or
      isopropanol. The retention behavior and selectivity of these chiral stationary
      phases were examined in isocratic normal phase mode. The results indicate that
      cellulose derivatives have higher enantioselectivity than amylose derivatives for
      the separation of racemic beta-amino ketones.

PMID- 25752941
TI  - Photothermally reprogrammable buckling of nanocomposite gel sheets.
AB  - Patterning deformation within the plane of thin elastic sheets represents a
      powerful tool for the definition of complex and stimuli-responsive 3D buckled
      shapes. Previous experimental methods, however, have focused on sheets that
      access a limited number of shapes pre-programmed into the sheet, restricting the
      degree of dynamic control. Here, we demonstrate on-demand reconfigurable buckling
      of poly(N-isopropylacrylamide-co-acrylic acid) (PNIPAM) hydrogel network films
      containing gold nanoparticles (AuNPs) by patterned photothermal deswelling.
      Predictable, easily controllable, and reversible transformations from a single
      flat gel sheet to numerous different three-dimensional forms are shown.
      Importantly, the response time is limited by poroelastic mass transport, rather
      than photochemical switching kinetics, enabling reconfiguration of shape on
      timescales of several seconds, with further increases in speed possible by
      reducing film thickness. 

PMID- 25752942
TI  - Catalytic dimer nanomotors: continuum theory and microscopic dynamics.
AB  - Synthetic chemically-powered motors with various geometries have potentially new
      applications involving dynamics on very small scales. Self-generated
      concentration and fluid flow fields, which depend on geometry, play essential
      roles in motor dynamics. Sphere-dimer motors, comprising linked catalytic and
      noncatalytic spheres, display more complex versions of such fields, compared to
      the often-studied spherical Janus motors. By making use of analytical continuum
      theory and particle-based simulations we determine the concentration fields, and
      both the complex structure of the near-field and point-force dipole nature of the
      far-field behavior of the solvent velocity field that are important for studies
      of collective motor motion. We derive the dependence of motor velocity on
      geometric factors such as sphere size and dimer bond length and, thus, show how
      to construct motors with specific characteristics. 

PMID- 25752943
TI  - An atmospheric origin of the multi-decadal bipolar seesaw.
AB  - A prominent feature of recent climatic change is the strong Arctic surface
      warming that is contemporaneous with broad cooling over much of Antarctica and
      the Southern Ocean. Longer global surface temperature observations suggest that
      this contrasting pole-to-pole change could be a manifestation of a multi-decadal
      interhemispheric or bipolar seesaw pattern, which is well correlated with the
      North Atlantic sea surface temperature variability, and thus generally
      hypothesized to originate from Atlantic meridional overturning circulation
      oscillations. Here, we show that there is an atmospheric origin for this seesaw
      pattern. The results indicate that the Southern Ocean surface cooling (warming)
      associated with the seesaw pattern is attributable to the strengthening
      (weakening) of the Southern Hemisphere westerlies, which can be traced to
      Northern Hemisphere and tropical tropospheric warming (cooling). Antarctic ozone
      depletion has been suggested to be an important driving force behind the recently
      observed increase in the Southern Hemisphere's summer westerly winds; our results
      imply that Northern Hemisphere and tropical warming may have played a triggering
      role at an stage earlier than the first detectable Antarctic ozone depletion, and
      enhanced Antarctic ozone depletion through decreasing the lower stratospheric
      temperature. 

PMID- 25752944
TI  - Diminished appetitive startle modulation following targeted inhibition of
      prefrontal cortex.
AB  - From an evolutionary perspective the startle eye-blink response forms an integral
      part of the human avoidance behavioral repertoire and is typically diminished by
      pleasant emotional states. In major depressive disorder (MDD) appetitive
      motivation is impaired, evident in a reduced interference of positive emotion
      with the startle response. Given the pivotal role of frontostriatal
      neurocircuitry in orchestrating appetitive motivation, we hypothesized that
      inhibitory transcranial magnetic stimulation (TMS) would reduce appetitive
      neuromodulation in a manner similar to MDD. Based on a pre-TMS functional MRI
      (fMRI) experiment we selected the left dorsolateral and dorsomedial prefrontal
      cortices as target regions for subsequent sham-controlled inhibitory theta-burst
      TMS (TBS) in 40 healthy male volunteers. Consistent with our hypothesis, between
      group comparisons revealed a TBS-induced inhibition of appetitive
      neuromodulation, manifest in a diminished startle response suppression by hedonic
      stimuli. Collectively, our results suggest that functional integrity of left
      dorsolateral and dorsomedial prefrontal cortex is critical for mediating a
      pleasure-induced down-regulation of avoidance responses which may protect the
      brain from a depressogenic preponderance of defensive stress. 

PMID- 25752945
TI  - Paracrine Factors Secreted by MSCs Promote Astrocyte Survival Associated With
      GFAP Downregulation After Ischemic Stroke via p38 MAPK and JNK.
AB  - Astrocytes are critical for ischemic stroke, and understanding their role in
      mesenchymal stem cell (MSC)-mediated protection against ischemic injury is
      important. The paracrine capacity of MSCs has been proposed as the principal
      mechanism contributing to the protection and repair of brain tissue. In the
      present study, an in vitro oxygen-glucose deprivation (OGD) model was used to
      mimic ischemic injury. OGD-induced astrocytes were reperfused with MSC
      conditioned medium (MSC-CM) or co-cultured with MSCs for 24 h to create an
      environment abundant in paracrine factors. The results indicated that both
      situations could protect astrocytes from apoptosis, increase cell metabolic
      activity, and reduce glial fibrillary acidic protein (GFAP) overexpression;
      however, the effects of co-culturing with MSCs were more positive. Paracrine
      factors suppressed the activation of p38 MAPK, JNK, and their downstream targets
      p53 and STAT1. Inhibition of p38 MAPK, JNK, p53, and STAT1 attenuated astrocyte
      injury and/or GFAP upregulation. Activation of p38 MAPK and JNK suppressed the
      beneficial effects of paracrine factors, resulting in decreased survival and GFAP
      overexpression. These results suggest that paracrine factors inhibit p38 MAPK and
      JNK, and most likely by regulating their downstream targets, p53 and STAT1, to
      promote astrocyte survival associated with GFAP downregulation after ischemic
      stroke in vitro.

PMID- 25752948
TI  - Neuroinflammation: Targeting neuroinflammation through inhibition of NLRP3.

PMID- 25752947
TI  - Anger, hostility, internalizing negative emotions, and intimate partner violence
      perpetration: A meta-analytic review.
AB  - Prior reviews have identified elevated trait anger as a risk factor for intimate
      partner violence (IPV) perpetration. Given that 10 years have passed since the
      last comprehensive review of this literature, we provide an updated meta-analytic
      review examining associations among anger, hostility, internalizing negative
      emotions, and IPV for male and female perpetrators. One hundred and five effect
      sizes from 64 independent samples (61 studies) were included for analysis. IPV
      perpetration was moderately associated with the constructs of anger, hostility,
      and internalizing negative emotions. This association appeared stronger for those
      who perpetrated moderate to severe IPV compared to those who perpetrated low to
      moderate IPV, and did not vary across perpetrator sex, measurement method,
      relationship type, or perpetrator population. Implications and limitations of
      findings were reviewed in the context of theoretical models of IPV, and future
      directions for empirical and clinical endeavors were proposed.

PMID- 25752949
TI  - Stroke: Stroke outcomes after 90 days-out of sight, out of mind?

PMID- 25752950
TI  - Neuromuscular disease: CRISPR/Cas9 gene-editing platform corrects mutations
      associated with Duchenne muscular dystrophy.

PMID- 25752951
TI  - Movement disorders: Friedreich ataxia today-preparing for the final battle.

PMID- 25752952
TI  - Antibacterial and membrane-damaging activities of mannosylated bovine serum
      albumin.
AB  - The aim of this study was to test whether mannosylated BSA (Man-BSA) exerts
      antibacterial activity on Escherichia coli (gram-negative bacteria) and
      Staphylococcus aureus (gram-positive bacteria) via its membrane-damaging effect.
      Man-BSA caused inhibition of growth of E. coli and S. aureus. Moreover,
      bactericidal action of Man-BSA on E. coli and S. aureus positively correlated
      with the increase in membrane permeability of the bacterial cells. Morphological
      examination showed that Man-BSA disrupted bacterial membrane integrity.
      Destabilization of the lipopolysaccharide (LPS) layer and inhibition of
      lipoteichoic acid (LTA) biosynthesis in the cell wall increased the bactericidal
      effect of Man-BSA on E. coli and S. aureus. Man-BSA also induced leakage and
      fusion of membrane-mimicking liposomes in E. coli and S. aureus. Man-BSA showed
      similar binding affinity for LPS and LTA. LPS and LTA strongly suppressed the
      membrane-damaging activity of Man-BSA, whereas an increase in the Man-BSA
      concentration attenuated the inhibitory action of LPS and LTA. Taken together,
      our data indicate that Man-BSA's bactericidal activity depends strongly on its
      ability to induce membrane permeability. Moreover, the bactericidal action of Man
      BSA proven in this study suggests that Man-BSA may serve as a prototype for the
      development of anti-infective agents targeting E. coli and S. aureus.

PMID- 25752953
TI  - Renin-angiotensin system contributes to naive T-cell migration in vivo.
AB  - Angiotensin II (Ang II) plays an important role in the regulation of the T-cell
      response during inflammation. However, the cellular mechanisms underlying the
      regulation of lymphocytes under physiologic conditions have not yet been studied.
      Here, we tested the influence of Ang II on T-cell migration using T cells from
      BALB/c mice. The results obtained in vivo showed that when Ang II production or
      the AT1 receptor were blocked, T-cell counts were enhanced in blood but decreased
      in the spleen. The significance of these effects was confirmed by observing that
      these cells migrate, through fibronectin to Ang II via the AT1 receptor. We also
      observed a gradient of Ang II from peripheral blood to the spleen, which explains
      its chemotactic effect on this organ. The following cellular mechanisms were
      identified to mediate the Ang II effect: upregulation of the chemokine receptor
      CCR9; upregulation of the adhesion molecule CD62L; increased production of the
      chemokines CCL19 and CCL25 in the spleen. These results indicate that the higher
      levels of Ang II in the spleen and AT1 receptor activation contribute to
      migration of naive T cells to the spleen, which expands our understanding on how
      the Ang II/AT1 receptor axis contributes to adaptive immunity.

PMID- 25752954
TI  - The conserved core enzymatic activities and the distinct dynamics of polyomavirus
      large T antigens.
AB  - Several human polyomaviruses including JCV, BKV and TSV are associated with
      diseases, particularly in immunosuppressed patients. While the large T antigen
      (LT) encoded by the monkey polyomavirus SV40 is well studied, and possesses
      intrinsic ATPase and DNA helicase activities, the LTs of the human polyomaviruses
      are relatively uncharacterized. In order to evaluate whether these enzymatic
      activities, which are required for viral DNA replication, are conserved between
      polyomaviruses, we performed a comparative study using the LTs from JCV, TSV and
      SV40. The ATPase and DNA helicase activities and the interaction with the
      cellular tumor suppressor p53 were assayed for the purified Zn-ATPase domains of
      the three LTs. We found that all Zn-ATPases were active ATPases. The Zn-ATPase
      domains also functioned as DNA helicases, although the measured kinetic constants
      differed among the three proteins. In addition, when tested against four small
      molecule ATPase inhibitors, the Zn-ATPase domains of TSV was more resistant than
      that of SV40 and JCV. Our results show that, while LTs from JCV and TSV share the
      core ATPase and DNA helicase activities, they possess important functional
      differences that might translate into their respective abilities to infect and
      replicate in hosts.

PMID- 25752955
TI  - Air contamination for predicting wound contamination in clean surgery: A large
      multicenter study.
AB  - BACKGROUND: The best method to quantify air contamination in the operating room
      (OR) is debated, and studies in the field are controversial. We assessed the
      correlation between 2 types of air sampling and wound contaminations before
      closing and the factors affecting air contamination. METHODS: This multicenter
      observational study included 13 ORs of cardiac and orthopedic surgery in 10
      health care facilities. For each surgical procedure, 3 microbiologic air counts,
      3 particles counts of 0.3, 0.5, and 5 MUm particles, and 1 bacteriologic sample
      of the wound before skin closure were performed. We collected data on surgical
      procedures and environmental characteristics. RESULTS: Of 180 particle counts
      during 60 procedures, the median log10 of 0.3, 0.5, and 5 MUm particles was 7
      (interquartile range [IQR], 6.2-7.9), 6.1 (IQR, 5.4-7), and 4.6 (IQR, 0-5.2),
      respectively. Of 180 air samples, 50 (28%) were sterile, 90 (50%) had 1-10 colony
      forming units (CFU)/m(3) and 40 (22%) >10 CFU/m(3). In orthopedic and cardiac
      surgery, wound cultures at closure were sterile for 24 and 9 patients, 10 and 11
      had 1-10 CFU/100 cm(2), and 0 and 6 had >10 CFU/100 cm(2), respectively (P <
      .01). Particle sizes and a turbulent ventilation system were associated with an
      increased number of air microbial counts (P < .001), but they were not associated
      with wound contamination (P = .22). CONCLUSIONS: This study suggests that
      particle counting is a good surrogate of airborne microbiologic contamination in
      the OR.

PMID- 25752956
TI  - Discrepancy in perceptions regarding patient participation in hand hygiene
      between patients and health care workers.
AB  - BACKGROUND: Patient participation in hand hygiene programs is regarded as an
      important component of hand hygiene improvement, but the feasibility of the
      program is still largely unknown. We examined the perceptions of
      patients/families and health care workers (HCWs) with regard to patient
      participation in hand hygiene. METHODS: A cross-sectional survey of
      patients/families as well as physicians and nurses was performed using an
      anonymous, self-administered questionnaire in a 1,000-bed teaching hospital in
      South Korea. RESULTS: A total of 152 physicians, 387 nurses, and 334
      patients/families completed the survey. The overall response rate was 84%, 85%,
      and more than 60% among physicians, nurses, and patients/families, respectively.
      Whereas 75% of patients/families wished to ask HCWs to clean their hands if they
      did not do so themselves, only 26% of physicians and 31% of nurses supported the
      participation of patients (P < .001). The most common reason why HCWs disagreed
      with patient participation was concern about negative effects on their
      relationship with patients (54%). Regarding the method of patient involvement,
      patients preferred to assess hand hygiene performance, whereas physicians
      preferred patients to ask directly. CONCLUSIONS: There was a significant
      discrepancy in perceptions regarding patient participation between
      patients/families and HCWs. Enhanced understanding and acceptance of any new
      program by both patients and HCWs before its introduction are needed for
      successful implementation.

PMID- 25752957
TI  - Molecular characteristics of Staphylococcus aureus isolated from employees,
      children, and environmental surfaces in Iowa child daycare facilities.
AB  - BACKGROUND: Infectious agents have the potential to thrive in child daycare
      facilities. Asymptomatic Staphylococcus aureus carriage is a risk factor for
      developing infection and contributes to transmission. METHODS: We collected swabs
      from 110 employees, 111 unexposed adults, 81 children, and 214 environmental
      surfaces at 11 Iowa daycare facilities. S aureus isolates were characterized
      using antibiotic resistance profiles and Staphylococcal protein A typing.
      Staphylococcal protein A types were grouped into cluster complexes using the
      Based Upon Repeat Pattern algorithm. RESULTS: All isolates (from 38 employees, 37
      unexposed adults, 16 children, and 19 surfaces) were characterized. Daycare
      employees were more likely to carry erythromycin-resistant S aureus than
      unexposed adults (odds ratio, 3.7; 95% confidence interval, 1.1-12.7; P = .033).
      Isolates were genetically heterogeneous, although isolates from employees
      appeared more clonal than those from unexposed adults. Strains associated with
      ST8 were identified in 5 daycare facilities and 3 unexposed adults. CONCLUSIONS:
      S aureus isolates collected from employees, children, and surfaces of daycare
      facilities are genetically heterogeneous, but contain strains associated with
      community-associated methicillin-resistant S aureus. This suggests that daycare
      facilities can serve as reservoirs for community-associated methicillin-resistant
      S aureus and facilitate genetic exchange. Employees may be at increased risk of
      carrying antibiotic-resistant strains, indicating more research is necessary into
      this occupational group.

PMID- 25752958
TI  - Integrin beta1 controls VE-cadherin localization and blood vessel stability.
AB  - Angiogenic blood vessel growth requires several distinct but integrated cellular
      activities. Endothelial cell sprouting and proliferation lead to the expansion of
      the vasculature and give rise to a highly branched, immature plexus, which is
      subsequently reorganized into a mature and stable network. Although it is known
      that integrin-mediated cell-matrix interactions are indispensable for embryonic
      angiogenesis, little is known about the function of integrins in different steps
      of vascular morphogenesis. Here, by investigating the integrin beta1-subunit with
      inducible and endothelial-specific gene targeting in the postnatal mouse retina,
      we show that beta1 integrin promotes endothelial sprouting but is a negative
      regulator of proliferation. In maturing vessels, integrin beta1 is indispensable
      for proper localization of VE-cadherin and thereby cell-cell junction integrity.
      The sum of our findings establishes that integrin beta1 has critical functions in
      the growing and maturing vasculature, and is required for the formation of
      stable, non-leaky blood vessels. 

PMID- 25752959
TI  - The real world cost and health resource utilization associated to manic episodes:
      The MANACOR study.
AB  - INTRODUCTION: Bipolar disorder is a relapsing-remitting condition affecting
      approximately 1-2% of the population. Even when the treatments available are
      effective, relapses are still very frequent. Therefore, the burden and cost
      associated to every new episode of the disorder have relevant implications in
      public health. The main objective of this study was to estimate the associated
      health resource consumption and direct costs of manic episodes in a real world
      clinical setting, taking into consideration clinical variables. METHODS: Bipolar
      I disorder patients who recently presented an acute manic episode based on DSM-IV
      criteria were consecutively included. Sociodemographic variables were
      retrospectively collected and during the 6 following months clinical variables
      were prospectively assessed (YMRS,HDRS-17,FAST and CGI-BP-M). The health resource
      consumption and associate cost were estimated based on hospitalization days,
      pharmacological treatment, emergency department and outpatient consultations.
      RESULTS: One hundred sixty-nine patients patients from 4 different university
      hospitals in Catalonia (Spain) were included. The mean direct cost of the manic
      episodes was ?4,771. The 77% (?3,651) was attributable to hospitalization costs
      while 14% (?684) was related to pharmacological treatment, 8% (?386) to
      outpatient visits and only 1% (?50) to emergency room visits. The hospitalization
      days were the main cost driver. An initial FAST score>41 significantly predicted
      a higher direct cost. CONCLUSIONS: Our results show the high cost and burden
      associated with BD and the need to design more cost-efficient strategies in the
      prevention and management of manic relapses in order to avoid hospital
      admissions. Poor baseline functioning predicted high costs, indicating the
      importance of functional assessment in bipolar disorder.

PMID- 25752960
TI  - High infiltration of tumor-associated macrophages is associated with a poor
      response to chemotherapy and poor prognosis of patients undergoing neoadjuvant
      chemotherapy for esophageal cancer.
AB  - BACKGROUND AND OBJECTIVE: Tumor-associated macrophages (TAMs) are well known to
      have distinct roles in tumor progression and metastasis. However, the role of
      TAMs in chemoresistance has not been fully investigated. The aim of this study is
      to examine whether TAMs, especially M2 macrophages, are associated with the tumor
      response to chemotherapy with esophageal cancers. METHODS: Using 210 tissues from
      patients with esophageal cancer who underwent surgery, we calculated the number
      of intratumoral CD68(+) macrophages, CD163(+) macrophages, and CD8(+) lymphocytes
      using immunohistochemistry. CD68 and CD163 were used as markers for whole
      macrophages and M2 macrophages, respectively. RESULTS: Infiltration of CD68(+)
      macrophages and CD163(+) macrophages was significantly associated with tumor
      depth, lymphatic invasion, and venous invasion. High infiltration of CD68(+)
      macrophages and CD163(+) macrophages was significantly associated with poor
      prognosis for patients undergoing neoadjuvant chemotherapy. Regarding the
      response to chemotherapy, high infiltration of CD68(+) and CD163(+) macrophages
      had a significant association with poor response to chemotherapy, both clinically
      and pathologically (P < 0.001, P < 0.001). Multivariate analysis showed that
      infiltration of CD163(+) macrophages was an independent prognostic factor in
      patients undergoing neoadjuvant chemotherapy. CONCLUSIONS: Infiltration of TAMs,
      especially M2 macrophages, is associated with a poor response to chemotherapy and
      poor prognosis of patients with esophageal cancer.

PMID- 25752961
TI  - In vitro and preliminary in vivo toxicity screening of high-surface-area TiO2
      chondroitin-4-sulfate nanocomposites for bone regeneration application.
AB  - The goal of this study was to prepare nontoxic, biomimetic TiO2/chondroitin-4
      sulfate nanocomposites with osteointegration ability for biomedical applications.
      Nanocomposites with higher surface area were subjected to bioactivity study and
      obtained bone-like layer with stoichiometric Ca/P ratio of 1.64 and 1.66. The
      susceptibility of nanocomposites against Staphylococcus aureus (~16 mm) and
      Escherichia coli (~12 mm) is favorable in preventing the risk of bone diseases
      and postoperative infections. Adequate swelling and degradations properties were
      favorably achieved to reduce the risk of nanoparticle accumulation in cell
      organelles. Moreover, the toxicity in AGS cell line and biocompatibility in
      osteoblast-like MG-63 cell line showed no significant mitochondrial damage. In
      addition, the in vitro expression of osteoblast inducing genes (OCN, OPN, ALP and
      COL 1) and their up-regulation, and 20% of increased hatching rate in preliminary
      in vivo (zebrafish) analysis were favorable for the nanocomposite at the ratio of
      2:0.50 than pure TiO2. Hence, it can be concluded that among the prepared
      nanocomposites TCs.5 is a promising biomimetic biomaterial that can be used for
      advanced orthopedic research and other applications.

PMID- 25752962
TI  - Fatty acid trafficking in starved cells: regulation by lipid droplet lipolysis,
      autophagy, and mitochondrial fusion dynamics.
AB  - Fatty acids (FAs) provide cellular energy under starvation, yet how they mobilize
      and move into mitochondria in starved cells, driving oxidative respiration, is
      unclear. Here, we clarify this process by visualizing FA trafficking with a
      fluorescent FA probe. The labeled FA accumulated in lipid droplets (LDs) in well
      fed cells but moved from LDs into mitochondria when cells were starved. Autophagy
      in starved cells replenished LDs with FAs, increasing LD number over time.
      Cytoplasmic lipases removed FAs from LDs, enabling their transfer into
      mitochondria. This required mitochondria to be highly fused and localized near
      LDs. When mitochondrial fusion was prevented in starved cells, FAs neither
      homogeneously distributed within mitochondria nor became efficiently metabolized.
      Instead, FAs reassociated with LDs and fluxed into neighboring cells. Thus, FAs
      engage in complex trafficking itineraries regulated by cytoplasmic lipases,
      autophagy, and mitochondrial fusion dynamics, ensuring maximum oxidative
      metabolism and avoidance of FA toxicity in starved cells.

PMID- 25752963
TI  - A CRISPR/Cas9 vector system for tissue-specific gene disruption in zebrafish.
AB  - CRISPR/Cas9 technology of genome editing has greatly facilitated the targeted
      inactivation of genes in vitro and in vivo in a wide range of organisms. In
      zebrafish, it allows the rapid generation of knockout lines by simply injecting a
      guide RNA (gRNA) and Cas9 mRNA into one-cell stage embryos. Here, we report a
      simple and scalable CRISPR-based vector system for tissue-specific gene
      inactivation in zebrafish. As proof of principle, we used our vector with the
      gata1 promoter driving Cas9 expression to silence the urod gene, implicated in
      heme biosynthesis, specifically in the erythrocytic lineage. Urod targeting
      yielded red fluorescent erythrocytes in zebrafish embryos, recapitulating the
      phenotype observed in the yquem mutant. While F0 embryos displayed mosaic gene
      disruption, the phenotype appeared very penetrant in stable F1 fish. This vector
      system constitutes a unique tool to spatially control gene knockout and greatly
      broadens the scope of loss-of-function studies in zebrafish.

PMID- 25752964
TI  - Effect of oxidative stress on Rho kinase II and smooth muscle contraction in rat
      stomach.
AB  - Recent studies have shown that both Rho kinase signaling and oxidative stress are
      involved in the pathogenesis of a number of human diseases, such as diabetes
      mellitus, hypertension, and atherosclerosis. However, very little is known about
      the effect of oxidative stress on the gastrointestinal (GI) smooth muscle Rho
      kinase pathway. The aim of the current study was to investigate the effect of
      oxidative stress on Rho kinase II and muscle contraction in rat stomach. The
      peroxynitrite donor 3-morpholinosydnonimine (SIN-1), hydrogen peroxide (H2O2),
      and peroxynitrite were used to induce oxidative stress. Rho kinase II expression
      and ACh-induced activity were measured in control and oxidant-treated cells via
      specifically designed enzyme-linked immunosorbent assay (ELISA) and activity
      assay kits, respectively. Single smooth muscle cell contraction was measured via
      scanning micrometry in the presence or absence of the Rho kinase blocker, Y-27632
      dihydrochloride. All oxidant agents significantly increased ACh-induced Rho
      kinase II activity without affecting its expression level. Most important,
      oxidative stress induced by all three agents augmented ACh-stimulated muscle cell
      contraction, which was significantly inhibited by Y-27632. In conclusion,
      oxidative stress activates Rho kinase II and enhances contraction in rat gastric
      muscle, suggesting an important role in GI motility disorders associated with
      oxidative stress. 

PMID- 25752965
TI  - Effects of rehabilitation among patients with advances cancer: a systematic
      review.
AB  - BACKGROUND: In parallel with the rising incidence of cancer and improved
      treatment, there is a continuous increase in the number of patients living with
      cancer as a chronic condition. Many cancer patients experience long-term
      disability and require continuous oncological treatment, care and support. The
      aim of this review is to evaluate the most recent data on the effects of
      rehabilitation among patients with advanced cancer. MATERIAL AND METHODS: A
      systematic review was conducted according to Fink's model. Only randomized
      controlled trials (RCTs) published in 2009-2014 were included. Medline/PubMed and
      Cochrane databases were searched; five groups of keywords were used. The articles
      were evaluated for outcome and methodological quality. RESULTS: Thirteen RCTs
      (1169 participants) were evaluated. Most studies were on the effects of physical
      exercise in patients with advanced cancer (N = 7). Physical exercise was
      associated with a significant improvement in general wellbeing and quality of
      life. Rehabilitation had positive effects on fatigue, general condition, mood,
      and coping with cancer. CONCLUSIONS: Rehabilitation is needed also among patients
      with advanced disease and in palliative care. Exercise improves physical
      performance and has positive effects on several other quality of life domains.
      More data and RCTs are needed, but current evidence gives an indication that
      rehabilitation is suitable and can be recommended for patients living with
      advanced cancer.

PMID- 25752966
TI  - New and chronic use of hypnotics after diagnosis with early breast cancer. A
      retrospective cohort study.
AB  - BACKGROUND: To determine use and investigate factors associated with use of
      hypnotics the first year after a diagnosis with breast cancer. MATERIAL AND
      METHODS: A retrospective registry based cohort study linking clinical data from
      the Danish Breast Cancer Group with the National Prescription Drug Database and
      other health and administrative registries. We included 26 082 women diagnosed
      with early breast cancer as first time primary cancer during 1996-2006. Use of
      hypnotics was measured as redeemed prescriptions in the first year after
      diagnosis of early breast cancer. Prior use of hypnotics was defined as one or
      more prescriptions of hypnotics 13 months to 1 month before diagnosis, and
      chronic use was defined as four or more prescriptions. Hazard ratios (HRs) for
      clinical variables, treatment-related factors and sociodemographic factors were
      calculated. RESULTS: Among women with no prior history of hypnotic use, 17%
      became new users with 4% on a chronic level. Among prior users, 82% continued
      their use with one or more prescriptions of hypnotics and 15% increased their use
      to a chronic level. Significantly increased hazard ratios for use of hypnotics
      were seen with increasing age [age 50-59 years: HR 1.43 (95% CI 1.31-1.57), age
      60-69: HR 1.57 (95% CI 1.44-1.71)], increasing number of tumor positive lymph
      nodes [1-3 lymph nodes: HR 1.12 (95% CI 1.05-1.09), 4-9 lymph nodes: HR 1.11 (95%
      CI 1.02-1.29)], chemotherapy [HR 1.25 (95% CI 1.12-1.39)], somatic comorbidity
      [HR 1.31 (95% CI 1.21-1.42)] and use of antidepressants the year before breast
      cancer diagnosis [HR 1.97 (95% CI 1.85-2.10)]. CONCLUSION: This study detected a
      group of patients at great risk for initiating and increasing use of hypnotics
      and preventive and prophylactic mechanism should be investigated and initiated
      when this group of patients is seen in the clinical setting.

PMID- 25752967
TI  - High levels of physical activity are associated with lower levels of fatigue
      among lymphoma patients: Results from the longitudinal PROFILES registry.
AB  - BACKGROUND: Studies show a cross-sectional association between physical activity
      (PA) and fatigue among lymphoma cancer patients. However, few longitudinal
      studies have examined whether PA has a sustained effect on fatigue over time.
      PURPOSE: To examine the longitudinal relationship between PA and fatigue.
      METHODS: All living individuals diagnosed with lymphoma between 1999 and 2010 as
      registered by the Dutch population-based Eindhoven Cancer Registry received a
      questionnaire on three time points. Generalized linear mixed models were used to
      estimate the independent effects of PA on fatigue. RESULTS: PA and fatigue levels
      did not differ between patients short-term (< 1 year) and long-term after
      diagnosis (1-5 years or > 5 years). PA behavior was relatively constant over time
      with 84% of the patients meeting the Dutch PA guidelines at all assessment
      periods. Fatigue scores also remained fairly stable over time with 46% of the
      patients never being fatigued and 29% always being fatigued. Multivariate
      analyses showed that patients who met the PA guidelines scored 6.2 (95% CI 3.1
      9.2) points lower on total fatigue over time (between subject effect; p < 0.01),
      compared to patients not meeting PA guidelines. CONCLUSION: During a period of
      two years, PA and fatigue levels were rather stable within lymphoma patients.
      Patients who met the PA guidelines reported lower levels of fatigue compared to
      those not meeting the guidelines, which appeared to be a constant association
      over time. The observed association between PA and fatigue underlines the
      importance to focus upon physical training in the care of cancer patients.

PMID- 25752968
TI  - The role of personality in the course of health-related quality of life and
      disease-specific health status among colorectal cancer survivors: A prospective
      population-based study from the PROFILES registry.
AB  - BACKGROUND: Prospective studies in various cardiovascular populations show that
      Type D personality predicted impaired health-related quality of life (HRQoL) and
      disease-specific health status. We examined the effect of negative affectivity
      (NA), social inhibition (SI) and their combined effect (Type D personality) on
      HRQoL and disease-specific health status among colorectal cancer (CRC) patients.
      METHODS: CRC patients diagnosed between 2000 and 2009, as registered in the Dutch
      population-based Eindhoven Cancer Registry, received questionnaires on Type D
      personality (DS14), HRQoL (EORTC QLQ-C30) and disease-specific health status
      (EORTC QLQ-CR38) in 2010, 2011 and 2012. RESULTS: Response rates were 73% (n =
      2625), 83% (n = 1643) and 82% (n = 1458), respectively. Analyses were done on
      those completing at least two questionnaires (n = 1735). Individuals with Type D
      (NA+/SI+; 19%) and high NA (NA+/SI-; 11%) reported a significantly worse HRQoL
      and disease-specific health status compared to NA-/SI+ and NA-/SI-. Differences
      were stable over time. Linear mixed effects models showed that Type Ds had a
      lower quality of life, cognitive and emotional functioning, more insomnia,
      diarrhea, gastrointestinal, defecation and stoma-related problems and poor body
      image and future perspective compared to the reference group (NA-/SI-), even
      after controlling for sociodemographic and clinical variables. High NA
      individuals (NA+/SI-) reported similar poor health outcomes as Type Ds. However,
      they also reported lower social functioning and more fatigue, pain, micturition-
      and financial problems, while Type Ds reported more constipation, sexual problems
      and less sexual enjoyment. CONCLUSIONS: Type D personality and high NA both have
      a significant negative stable impact on HRQoL and disease-specific health status
      among CRC patients.

PMID- 25752969
TI  - Distress after a psychosocial cancer rehabilitation course. Main effects and
      effect modification in a randomised trial at 12 months of follow-up.
AB  - BACKGROUND: In 2002, the Danish Cancer Society opened a rehabilitation centre in
      which cancer patients were offered a free, six-day, multidimensional residential
      course. Our previous studies of the effects of this course at one and six months
      of follow-up showed no positive effect on distress. We investigated long-term
      effects at 12 months of follow-up and whether subgroups with fewer psychosocial
      resources received more benefit from the intervention than patients with better
      resources. MATERIAL AND METHODS: In two Danish counties, 507 patients with
      breast, prostate, colon or rectum cancer diagnosed within the past two years who
      had completed primary treatment were randomised to a six-day, multidimensional
      residential rehabilitation course or to standard care. Of these, 208 patients
      received the allocated intervention and 244 received the allocated control
      condition and were included in the analyses. Patients in both groups completed
      questionnaires at baseline and at one, six and 12 months of follow-up, including
      the 'Profile of Mood States short form', the 'General Self-efficacy' scale and a
      question on emotional support. At 12 months of follow-up, 179 participants in the
      intervention group and 195 in the control group provided data. RESULTS: No effect
      of the intervention was found on distress at 12 months of follow-up, even in
      subgroups with fewer psychosocial resources at baseline, i.e. greater baseline
      distress, poorer self-efficacy and less emotional support. CONCLUSION:
      Multidimensional rehabilitation programmes may not be effective in the treatment
      of distress. During the past few decades, studies of psychotherapy or psycho
      education in cancer patients have shown small to moderate effects. More focused
      rehabilitation programmes may be more effective.

PMID- 25752970
TI  - Family psychosocial risk screening guided by the Pediatric Psychosocial
      Preventative Health Model (PPPHM) using the Psychosocial Assessment Tool (PAT).
AB  - BACKGROUND: Although families of children with cancer and other serious medical
      conditions have documented psychosocial needs, the systematic identification of
      needs and delivery of evidence-based care remain challenges. Screening for
      multifaceted family psychosocial risk is a means by which psychosocial treatment
      needs for pediatric patients and their families can be identified in an effective
      and inclusive manner. MATERIAL AND METHODS: The Pediatric Psychosocial
      Preventative Health Model (PPPHM) is a model that can guide systematic assessment
      of family psychosocial risk. The Psychosocial Assessment Tool (PAT) is a brief
      parent report screener of psychosocial risk based on the PPPHM that can be used
      for families of infants through adolescents. The PPPHM and the PAT are described
      in this paper, along with a summary of data supporting systematic risk
      assessment. RESULTS: The PPPHM outlines three tiers of family psychosocial risk -
      Universal (low), Targeted (medium), and Clinical (high). The PAT is a validated
      measure of psychosocial risk. Scores on the PAT, derived from multiple sites and
      disease conditions, map on to the PPPHM with indications that one-half to two
      thirds of families score at the Universal level of risk based on the PAT.
      CONCLUSION: The PAT is a unique screener of psychosocial risk, both in terms of
      its breadth and underlying model (PPPHM), and its length and format. As an
      example of a means by which families can be screened early in the treatment
      process, PAT scores and corresponding PPPHM levels can provide direction for the
      delivery of evidence-based psychosocial care.

PMID- 25752971
TI  - Physical activity, risk of death and recurrence in breast cancer survivors: A
      systematic review and meta-analysis of epidemiological studies.
AB  - Strong evidence exists supporting the effect of lack of physical activity on the
      risk of developing breast cancer. However, studies examining the effects of
      physical activity on breast cancer outcomes, including survival and prognosis
      have been inconclusive. Therefore, the aim of the current study was to provide a
      systematic review and meta-analysis of studies investigating the association
      between physical activity and breast cancer recurrence and death. METHODS:
      PubMed, EMBASE, and CENTRAL databases were searched up to 18 October 2014.
      Reference lists of retrieved articles and relevant previous reviews were also
      searched. Observational studies that reported risk estimates for all-cause and/or
      breast cancer-related death and/or breast cancer recurrences by levels of
      physical activity, were included in the review. Random effects models were used
      to calculate pooled hazard ratios (HR) and 95% confidence intervals (CI) and to
      incorporate variation between studies. The Newcastle-Ottawa scale was used to
      critically appraise the risk of bias across studies. RESULTS: Twenty-two
      prospective cohort studies were eligible in this meta-analysis. During average
      follow-up periods ranging from 4.3 to 12.7 years there were 123 574 participants,
      6898 all-cause deaths and 5462 breast cancer outcomes (i.e. breast cancer-related
      deaths or recurrences). The average Newcastle-Ottawa score was six stars (range 4
      8). Compared to those who reported low/no lifetime recreational pre-diagnosis
      physical activity, participants who reported high lifetime recreational pre
      diagnosis physical activity levels had a significantly lower risk of all-cause
      (HR = 0.82, 95% CI 0.70-0.96, p < 0.05) and breast cancer-related death (HR =
      0.73, 95% CI 0.54-0.98, p < 0.05). Significant risk reductions for all-cause and
      breast cancer-related death was also demonstrated for more recent pre-diagnosis
      recreational physical activity (HR = 0.73, 95% CI 0.65-0.82, p < 0.001; and HR =
      0.84, 95% CI 0.73-0.97, p < 0.05, respectively), post-diagnosis physical activity
      (HR = 0.52, 95% CI 0.43-0.64, p < 0.01; and HR = 0.59, 95% CI 0.45-0.78, p <
      0.05, respectively) and meeting recommended physical activity guidelines (i.e. >=
      8 MET-h/wk) post-diagnosis (HR = 0.54, 95% CI 0.38-0.76, p < 0.01; and HR = 0.67,
      95% CI 0.50-0.90, p < 0.01, respectively). However, there was evidence of
      heterogeneity across lifetime recreational pre- and post-diagnosis physical
      activity analyses. Both pre-diagnosis (lifetime and more recent combined) and
      post-diagnosis physical activity were also associated with reduced risk of breast
      cancer events (breast cancer progression, new primaries and recurrence combined)
      (HR = 0.72 95% CI 0.56-0.91, p < 0.01; and HR = 0.79, 95% CI 0.63-0.98, p < 0.05,
      respectively). CONCLUSION: There is an inverse relationship between physical
      activity and all-cause, breast cancer-related death and breast cancer events. The
      current meta-analysis supports the notion that appropriate physical activity may
      be an important intervention for reducing death and breast cancer events among
      breast cancer survivors.

PMID- 25752972
TI  - Effect of mindfulness-based stress reduction on somatic symptoms, distress,
      mindfulness and spiritual wellbeing in women with breast cancer: Results of a
      randomized controlled trial.
AB  - BACKGROUND: Women with breast cancer experience different symptoms related to
      surgical or adjuvant therapy. Previous findings and theoretical models of mind
      body interactions suggest that psychological wellbeing, i.e. levels of distress,
      influence the subjective evaluation of symptoms, which influences or determines
      functioning. The eight-week mindfulness-based stress reduction (MBSR) program
      significantly reduced anxiety and depression in breast cancer patients in a
      randomized controlled trial (NCT00990977). In this study we tested the effect of
      MBSR on the burden of breast cancer related somatic symptoms, distress,
      mindfulness and spiritual wellbeing and evaluated possible effect modification by
      adjuvant therapy and baseline levels of, distress, mindfulness and spiritual
      wellbeing. MATERIAL AND METHODS: A population-based sample of 336 women Danish
      women operated for breast cancer stages I-III were randomized to MBSR or usual
      care and were followed up for somatic symptoms, distress, mindfulness skills and
      spiritual wellbeing post-intervention and after six and 12 months. Effect was
      tested by general linear regression models post-intervention, and after six and
      12 months follow-up and by mixed effects models for repeated measures of
      continuous outcomes. Effect size (Cohen's d) was calculated to explore clinical
      significance of effects among intervention group. Finally, modification of effect
      of MBSR on burden of somatic symptoms after 12 months' follow-up by adjuvant
      therapy and baseline levels of, distress, mindfulness and spiritual wellbeing
      were estimated. RESULTS: General linear regression showed a significant effect of
      MBSR on the burden of somatic symptoms post-intervention and after 6 months'
      follow-up. After 12 months' follow-up, no significant effect of MBSR on the
      burden of somatic symptoms was found in mixed effect models. A statistically
      significant effect of MBSR on distress was found at all time-points and in the
      mixed effect models. Significant effects on mindfulness were seen after six and
      12 months and no significant effect was observed for spiritual wellbeing. No
      significant modification of MBSR effect on somatic symptom burden was identified.
      CONCLUSION: This first report from a randomized clinical trial on the long-term
      effect of MBSR finds an effect on somatic symptom burden related to breast cancer
      after six but not 12 months follow-up providing support for MBSR in this patient
      group.

PMID- 25752973
TI  - Reproductive factors and risk of biliary tract cancer in a population-based
      study.
AB  - BACKGROUND: The strong female predominance of biliary tract cancer (BTC) may be
      related to reproductive factors. We aimed to clarify whether parity or age at
      first birth influence the risk of BTC. METHODS: This was a population-based, case
      control study including Swedish female and male cases of cancer of the
      gallbladder (GBC), extra hepatic bile ducts (EHCC), or the ampulla of Vater (AVC)
      between 1960 and 2008. For each case, 10 age- and sex-matched controls were
      randomly selected. Conditional logistic regression was used to calculate odds
      ratios (ORs) with 95% confidence intervals (CIs), adjusted for potential
      confounders. RESULTS: In total, 1169 cases of GBC, 432 cases of EHCC and 295
      cases of AVC were included. Multi- and nulliparous women and men had an increased
      risk of all tumor locations in the biliary tract compared to uniparous women and
      men, respectively. Whereas higher age at first birth was associated with a
      decreased risk of GBC in women, no such association was found in men. There were
      no clear differences in the risk of EHCC and AVC between women and men.
      CONCLUSION: Sex hormones may play a role in the etiology of GBC. The associations
      between reproductive factors and EHCC and AVC are similar in women and men, which
      do not support the sex hormone hypothesis.

PMID- 25752974
TI  - Wage-subsidised employment as a result of permanently reduced work capacity in a
      nationwide cohort of patients diagnosed with haematological malignancies.
AB  - BACKGROUND: Patients with haematological malignancies have a poorer labour market
      prognosis than the general population. We have previously found that they have
      low rates of return to work, and a higher risk of being granted disability
      pension, than individuals without a history of these diseases. The aim of this
      study was to further investigate the labour market prognosis for these patients,
      by comparing the risk of being granted wage-subsidised (WS) employment as a
      result of permanently reduced work capacity among patients diagnosed with
      haematological malignancies to a reference cohort, and to determine if relative
      risks differ between subtypes of haematological malignancies. MATERIAL AND
      METHODS: We combined data from national registers on Danish patients diagnosed
      with haematological malignancies between 2000 and 2007 and a reference cohort
      without a history of these diseases. A total of 3194 patients and 28 627
      reference individuals were followed until they were granted WS employment,
      disability pension, anticipatory pension, old age pension, emigration, death or
      until 26 February 2012, whichever came first. RESULTS: A total of 310 (10%)
      patients and 795 (3%) reference individuals had their work capacity permanently
      reduced to an extent that they were granted WS employment during the follow-up
      period. Age- and gender-adjusted relative risks differed significantly between
      the subgroups of haematological malignancies, and four years after diagnosis they
      ranged from 2.47 (95% CI 1.46-4.16) for patients with Hodgkin lymphoma to 10.83
      (95% CI 7.15-16.40) for patients with chronic myeloid leukaemia. CONCLUSION: All
      eight subtypes of haematological malignancies were associated with an increased
      risk of being granted WS employment due to permanently reduced work capacity
      compared to the reference cohort. The relative risks differed according to
      haematological malignancy subtype, and the highest was found for patients with
      chronic myeloid leukaemia.

PMID- 25752975
TI  - Macrophage phagocytic activity toward adhering staphylococci on cationic and
      patterned hydrogel coatings versus common biomaterials.
AB  - Biomaterial-associated-infection causes failure of biomaterial implants. Many new
      biomaterials have been evaluated for their ability to inhibit bacterial
      colonization and stimulate tissue-cell-integration, but neglect the role of
      immune cells. This paper compares macrophage phagocytosis of adhering
      Staphylococcus aureus on cationic-coatings and patterned poly(ethylene)glycol
      hydrogels versus common biomaterials and stainless steel in order to identify
      surface conditions that promote clearance of adhering bacteria. Staphylococci
      were allowed to adhere and grow on the materials in a parallel-plate-flow
      chamber, after which murine macrophages were introduced. From the decrease in the
      number of adhering staphylococci, phagocytosis-rates were calculated, and total
      macrophage displacements during an experiment determined. Hydrophilic surfaces
      had the lowest phagocytosis-rates, while common biomaterials had intermediate
      phagocytosis-rates. Patterning of poly(ethylene)glycol-hydrogel coatings
      increased phagocytosis-rates to the level of common biomaterials, while on
      cationic-coatings phagocytosis-rates remained relatively low. Likely,
      phagocytosis-rates on cationic coatings are hampered relative to common
      biomaterials through strong electrostatic binding of negatively-charged
      macrophages and staphylococci. On polymeric biomaterials and glass, phagocytosis
      rates increased with macrophage displacement, while both parameters increased
      with biomaterial surface hydrophobicity. Thus hydrophobicity is a necessary
      surface condition for effective phagocytosis. Concluding, next-generation
      biomaterials should account for surface effects on phagocytosis in order to
      enhance the ability of these materials to resist biomaterial-associated
      infection. 

PMID- 25752976
TI  - [Outpatient pediatric urology in France: A still under developed practice.
      Results of a survey of the French Section of pediatric Urology (SFUP)].
AB  - PURPOSE: Outpatient surgery is a very well adapted practice to the pediatric
      population. Our goal was to evaluate its actual development in the field of the
      pediatric urology. MATERIALS AND METHODS: A questionnaire was addressed to all
      the French pediatric surgery centers in which at least one surgeon was member of
      the French Section of Pediatric Urology. The questionnaire concerned the
      organization and the outpatient urology procedures performed during the years
      2011 and 2012. RESULTS: Thirty of the 34 approached centers returned the
      questionnaire. The total number of patients concerned in this study was of
      33,166. The practices were very variable among centers: the inferior limit of age
      for anesthesia ranged from 2 to 12 months and type of surgery was also
      heterogeneous. Foreskin surgery, orchiopexy for undescended testis, inguinal
      hernia, and endoscopic treatment of vesico-ureteral reflux were the only
      procedures performed for more than 60% of cases as outpatient surgery. Outpatient
      surgery is not well developed in hypospadias repair. Only five centers raised 60%
      of ambulatory procedures for distal cases. No serious complication related to the
      outpatient approach was reported. CONCLUSION: This survey demonstrated very
      heterogeneous practices among French pediatric urologic centers. According to the
      French guidelines about outpatient pediatric surgery, this type of care could be
      more developed if anesthesiologists and surgeons accepted to evolve in their
      practice.

PMID- 25752977
TI  - IL-35 expression in peripheral blood CD4(+) T cells from chronic hepatitis B
      virus-infected patients directly correlates with virus load.
AB  - Interleukin 35 (IL-35) functions in an anti-inflammatory fashion by inhibiting T
      cell proliferation, whereas CD4(+) T cells play an important role in cellular
      immunity. In a hepatitis B virus (HBV) infection, the viral proteins stimulate
      the immune system to generate antiviral molecules, which correlate to HBV DNA
      load. We investigated the impact of HBV DNA load on the expression of IL-35 mRNA
      in CD4(+) T cells, and the expression of IL-35 cytokine in serum of the patients
      with chronic HBV infection. Here we report that the frequency of circulating
      CD4(+) T cells correlates with the HBV DNA load in the serum of chronic hepatitis
      B (CHB) patients. An increased number of CD4(+) T cells were found in those
      patients with higher levels of HBV DNA. Regulatory T cells (T regs) also showed
      this trend, but circulating cytotoxic lymphocytes (CTLs) showed a negative
      correlation with serum HBV DNA load. In addition, significantly more IL-35 mRNA
      was found in the CD4(+) T cells of CHB patients, compared to healthy controls.
      Patients in the high viral load group showed increased levels of IL-35 mRNA,
      compared with those in the low viral load group. The level of IL-35 cytokine in
      the serum of CHB patients was significantly higher than in the healthy controls
      and in those infected with HBV, the patients with a higher viral load had more
      serum IL-35 cytokines, compared to those with a lower viral load. Our study
      suggests that increased serum IL-35 could be directly related to increased levels
      of IL-35 mRNA in CD4(+) T cells and HBV DNA load in CHB patients. The possible
      role of IL-35 as an immune regulator in chronic HBV infection should be
      investigated further.

PMID- 25752978
TI  - [Initial experience of first 225 flexible ureteroscopy with laser lithotripsy in
      a primary care hospital].
AB  - INTRODUCTION: During the last decade, the advent of flexible ureteroscopy with
      laser lithotripsy has revolutionized the management of upper urinary tract
      stones. Our center is a primary care hospital that is equipped with this
      technology since January 2011. This study reported our initial experience of
      first 225 cases. MATERIEL AND METHODS: This study is a descriptive, retrospective
      and monocentric analysis. The first 225 cases, operated consecutively by 3
      surgeons during 26 months, were analyzed. We have used 2 flexible ureteroscopes
      (1 digital, 1 optical). Laser source was an Holmium laser (Stonelight) at a power
      of 5 watts. RESULTS: The mean age was 53 years (+/- 10.2) and the mean stones
      size was 11 mm (2.3). In 49% of cases, ureteroscopy was chosen for the first,
      without prior treatment. In 59% of cases, ureteroscopy was used after failure of
      other treatment (ESWL in 70% of cases). The mean operative time was 72 minutes
      (+/- 16.6) and the mean length of stay was 2.6 days (+/- 0.8). The first session
      of ureteroscopy was a success in 93% of cases without residual fragments after 1
      month. The frequency of postoperative complications was estimated at 8% (Clavien
      I and II). CONCLUSION: Flexible ureteroscopy with laser lithotripsy was a safe
      and effective technique, allowing the treatment of all upper urinary tract
      stones, especially on failure of other treatment. Its place in the first
      intention is widespread in our exercise, especially among obese patients,
      patients on anticoagulant therapy or with stone of the lower pole.

PMID- 25752979
TI  - Self-perspective inhibition deficits cannot be explained by general executive
      control difficulties.
AB  - Understanding other people's point of view is crucial for successful social
      interaction but can be particularly challenging in situations where the other
      person's point view conflicts with our own view. Such situations require
      executive control processes that help us resist interference from our own
      perspective. In this study, we examined how domain-general these executive
      processes are. We report the performance of two pairs of brain-damaged patients
      who had sustained lesions in different areas of the prefrontal cortex and who
      showed deficits in classic executive function tasks. The patients were presented
      with desire reasoning tasks in which two sources of executive control were
      manipulated: the need to resist interference from one's own desire when inferring
      someone else's conflicting desire and the need to resist interference from the
      ascription of an approach motivation when inferring an avoidance-desire. The
      pattern of performance of the two pairs of patients conformed to a classic double
      dissociation with one pair of patients showing a deficit in resisting
      interference from their own perspective but not from the ascription of an
      approach motivation while the other pair of patients showed the opposite profile.
      The results are discussed in relation to the specificity of the processes
      recruited when we resist interference from our own perspective. 

PMID- 25752980
TI  - Emerging evidence contradicts the hypothesis that bilingualism delays dementia
      onset. A Commentary on "age of dementia diagnosis in community dwelling bilingual
      and monolingual Hispanic Americans" by Lawton et al., 2015.

PMID- 25752981
TI  - Research Agenda: The Effects of Responsible-Conduct-of-Research Training on
      Attitudes.
AB  - Requirements for training in responsible conduct of research have significantly
      increased over the past 25 years, despite the absence of evidence for a
      substantial impact. One of the challenges has been to choose among the many
      possible goals that might define outcomes. Although much of the focus of research
      has been on changes in knowledge or skills, a case can be made that attitudes and
      perceptions are at least as important. Based on a recently completed pilot study,
      the authors propose several areas for research to clarify not only what but also
      how attitudes and perceptions would be usefully assessed. 

PMID- 25752982
TI  - Loratadine analogues as MAGL inhibitors.
AB  - Compound 12a (JZP-361) acted as a potent and reversible inhibitor of human
      recombinant MAGL (hMAGL, IC50=46 nM), and was found to have almost 150-fold
      higher selectivity over human recombinant fatty acid amide hydrolase (hFAAH,
      IC50=7.24 MUM) and 35-fold higher selectivity over human alpha/beta-hydrolase-6
      (hABHD6, IC50=1.79 MUM). Additionally, compound 12a retained H1 antagonistic
      affinity (pA2=6.81) but did not show cannabinoid receptor activity, when tested
      at concentrations ? 10 MUM. Hence, compound 12a represents a novel dual-acting
      pharmacological tool possessing both MAGL-inhibitory and antihistaminergic
      activities.

PMID- 25752983
TI  - Syntheses of chondroitin sulfate tetrasaccharide structures containing 4,6
      disulfate patterns and analysis of their interaction with glycosaminoglycan
      binding protein.
AB  - Chondroitin sulfate tetrasaccharide ligand conjugates, namely GlcA-GalNAc6S-GlcA
      GalNAc4S6S (CS-C+E) 1, GlcA2S-GalNAc6S-GlcA2S-GalNAc4S6S (CS-D+T) 2, GlcA
      GalNAc4S6S-GlcA-GalNAc4S (CS-E+A) 3, GlcA-GalNAc4S6S-GlcA-GalNAc6S (CS-E+C) 4,
      and GlcA-GalNAc4S6S-GlcA-GalNAc4S6S (CS-E+E) 5, were systematically synthesized
      using a disaccharide building block 6. Synthesized CS tetrasaccharide structures
      were immobilized onto gold-coated chips to prepare array-type sugar chips, and
      the binding properties of protein were evaluated by surface plasmon resonance
      imaging biosensor. CS-D+T, CS-E+A, CS-E+C, and CS-E+E showed greater affinity for
      basic fibroblast growth factor than did other tetrasaccharides (CS-C+D, C+E,
      D+D).

PMID- 25752984
TI  - Design and synthesis of a novel series of [1-(4-hydroxy-benzyl)-1H-indol-5-yloxy]
      acetic acid compounds as potent, selective, thyroid hormone receptor beta
      agonists.
AB  - The design, synthesis, and structure activity relationships for a novel series of
      indoles as potent, selective, thyroid hormone receptor beta (TRbeta) agonists is
      described. Compounds with >50* binding selectivity for TRbeta over TRalpha were
      generated and evaluation of compound 1c from this series in a model of
      dyslipidemia demonstrated positive effects on plasma lipid endpoints in vivo.

PMID- 25752985
TI  - Low aspect ratio micropores for single-particle and single-cell analysis.
AB  - This paper describes microparticle and bacterial translocation studies using low
      aspect ratio solid-state micropores. Micropores, 5 MUm in diameter, were
      fabricated in 200 nm thick free-standing silicon nitride membranes, resulting in
      pores with an extremely low aspect ratio, nominally 0.04. For microparticle
      translocation experiments, sulfonated polystyrene microparticles and magnetic
      microbeads in size range of 1-4 MUm were used. Using the microparticle
      translocation characteristics, we find that particle translocations result in a
      change only in the pore's geometrical resistance while the access resistance
      remains constant. Furthermore, we demonstrate the ability of our micropore to
      probe high-resolution shape information of translocating analytes using
      concatenated magnetic microspheres. Distinct current drop peaks were observed for
      each microsphere of the multibead architecture. For bacterial translocation
      experiments, nonflagellated Escherichia coli (strain HCB 5) and wild type
      flagellated Salmonella typhimurium (strain SJW1103) were used. Distinct current
      signatures for the two bacteria were obtained and this difference in
      translocation behavior was attributed to different surface protein distributions
      on the bacteria. Our findings may help in developing low aspect ratio pores for
      high-resolution microparticle characterization and single-cell analysis. 

PMID- 25752986
TI  - Previous hemodialysis access improves functional outcomes of the proximal radial
      artery fistula in males.
AB  - BACKGROUND: The proximal radial artery fistula (PRA) has been established as an
      early viable surgical option for arteriovenous fistula creation. The overall
      assisted primary patency reported in the literature approaches 100% at 1 year. We
      hypothesize that this excellent patency does not represent a functional result
      when seen in light of successful cannulation and fistula utilization. METHODS: We
      retrospectively queried our Veterans Administration Hospital operative database
      to identify 284 male patients who had 571 access procedures performed by a senior
      vascular surgeon attending (R.K.D.) from January 1, 2003, to December 31, 2008.
      Operative details, patient comorbidities, fistula maturation time (time to first
      cannulation), functional patency (date of access to abandonment, revision to
      another fistula type, conversion to a prosthetic graft, thrombosis of the
      fistula, conversion to peritoneal dialysis, renal transplant, or patient death),
      and total duration (creation of the fistula to the end of its functional patency)
      were collected and analyzed. RESULTS: A total of 144 PRAs were placed during the
      study period. In all, 87 patients underwent primary proximal radial artery
      fistula (P-PRA) placement in a limb without previous access; 57 patients had a
      secondary proximal radial artery fistula (S-PRA) after a failed previous fistula
      or graft in the same limb. There were no differences between the 2 groups in
      terms of age, comorbidities, and operative details. A total of 91 patients
      (63.2%) were receiving hemodialysis at the time of P-PRA or S-PRA placement.
      Outcomes of P-PRA and S-PRA populations on hemodialysis were examined. There was
      increased cannulation success (33% vs. 55%; P = 0.00354, Fisher's exact test),
      functional patency (755.2 +/- 661.2 days vs. 405.4 +/- 531.9 days; P = 0.0220,
      Wilcoxon two-sample test), and total duration (859.5 +/- 650.7 days vs. 516.8 +/-
      547.2 days; P = 0.0361, Wilcoxon two-sample test) of S-PRA over P-PRA. There was
      no difference in endovascular interventions between the 2 groups (1.6 +/- 1.0
      interventions per access versus 1.1 +/- 0.7 interventions per access; P = 0.2109,
      Wilcoxon two-sample test). Subgroup analysis (analysis of variance) of the S-PRA
      group indicated that a patent but failing previous access in the same arm was not
      superior in terms of successful cannulation, functional patency, or total
      duration when compared with a thrombosed previous access. CONCLUSIONS: The PRA
      remains a viable first access procedure undertaken at our institution. Compared
      with the reported 12-month assisted primary patency of this fistula type, we
      found a small percentage of PRAs actually being accessed for successful
      hemodialysis treatment. The S-PRA appears to have a significantly higher
      successful cannulation rate, functional patency, and total duration time when
      compared with the P-PRA in patients receiving hemodialysis treatments. The
      mechanism of these improved outcomes is not known; considering patency or
      thrombosis of a previous access in the S-PRA group did not predict future access
      success in the same extremity.

PMID- 25752988
TI  - Insights into the development of a trauma short course for Australasian emergency
      medicine clinicians.

PMID- 25752987
TI  - Treatment of venous pulsatile tinnitus in younger women.
AB  - BACKGROUND: We present 7 cases of pulsatile tinnitus (PT) of venous origin in
      younger women seen over a period of 24 years and treated by Internal Jugular Bulb
      ligation. METHODS: All patients had a pulsatile bruit in one side of the neck
      that disappeared when gentle pressure over the internal jugular vein (IJV) caused
      it to collapse as seen in a duplex scan. Their computed tomography showed a
      dominant venous system with a high jugular bulb on the side of the bruit.
      RESULTS: The IJV was ligated under local anesthesia. Five patients in whom the
      ligation was done above the facial vein were cured. Two patients in whom the
      ligation was done below the facial vein experienced a decrease but not
      disappearance of the PT. CONCLUSIONS: Once other possible causes for PT have been
      discarded, ligation of the IJV above the facial vein cures this condition.

PMID- 25752989
TI  - 'I think other parents might. ...': Using a projective technique to explore
      parental supply of alcohol.
AB  - INTRODUCTION AND AIMS: A growing body of research indicates parental supply of
      alcohol to children and adolescents is common. The present study aimed to examine
      parents' reasons for supplying alcohol to adolescents that they may find hard to
      articulate or not be consciously aware of. DESIGN AND METHODS: A projective
      methodology was used, whereby respondents were asked to explain the thoughts and
      motivations of a gender-matched parent in a scenario in which the parent did or
      did not provide alcohol to their teenage child. Respondents were 97 mothers and
      83 fathers of teenagers who completed an anonymous online survey. Open-ended
      responses were coded thematically; t-tests were used to compare quantitative
      responses between the scenarios. RESULTS: The quantitative analysis found the
      parent who provided alcohol was less likely to be seen as making sure their child
      was safe and educating them about boundaries, but more likely to be seen as being
      a friend as well as a parent and (for females only) making sure their child fits
      in with others. The open-ended responses showed explanations for not providing
      alcohol most commonly focused on ensuring the child's safety, obeying the law,
      and setting rules and boundaries, and for providing alcohol focused on ensuring
      the child fit in with peers and beliefs about harm minimisation. DISCUSSION AND
      CONCLUSIONS: The findings suggest that these respondents (parents) harboured a
      number of misperceptions about underage drinking and experienced conflicts in
      weighing up the perceived benefits of providing alcohol to their children against
      the risks of adolescent drinking. [Jones SC, Magee C, Andrews K. 'I think other
      parents might. ...': Using a projective technique to explore parental supply of
      alcohol. Drug Alcohol Rev 2015;34:531-9].

PMID- 25752990
TI  - VV' Alternans Triplets on Near-Field ICD Intracardiac Electrogram is Associated
      with Mortality.
AB  - BACKGROUND: In heart failure patients with implantable cardioverter defibrillator
      (ICD) the risk of death from causes other than tachyarrhythmia is substantial.
      Benefit from ICD is determined by two competing risks: appropriate ICD shock or
      nonarrhythmic death. The goal of the study was to test predictors of competing
      outcomes. METHODS: Patients with structural heart disease (N = 234, mean age 58.5
      +/- 15.1; 71% men, 80% whites, 61% ischemic cardiomyopathy) and primary (75%) or
      secondary prevention ICD underwent a 5-minute baseline near-field electrogram (NF
      EGM) recording. VV' alternans triplets were quantified as a percentage of three
      sinus VV' cycles sequences of "short-long-short" or "long-short-long" order.
      Appropriate ICD shock for fast ventricular tachycardia (FVT, cycle length <=240
      ms)/ventricular fibrillation (VF) and composite nonarrhythmic death (pump failure
      death or heart transplant) served as competing outcomes. RESULTS: Over a median
      follow-up of 2.4 years, 26 patients (4.6% per person-year of follow-up) developed
      FVT/VF with ICD shock, and 35 (6.3% per person-year of follow-up) had
      nonarrhythmic death. In competing risk analysis, after adjustment for
      demographics, left ventricular ejection fraction, New York Heart Association
      class, cardiomyopathy type, use of class I antiarrhythmics, and diabetes,
      increased percentage of VV' alternans triplets (>69%) was associated with
      nonarrhythmic death (subhazard ratio [SHR] 2.09; 95% confidence interval [CI]
      1.03-4.23; P = 0.041), rather than with FVT/VF (SHR 1.05; 95% CI 0.45-2.46; P =
      0.901). Risk of nonarrhythmic death was especially high in diabetics with VV'
      alternans triplets in the highest quartile (SHR 3.46; 95% CI 1.41-8.50; P =
      0.007). CONCLUSION: In ICD patients with structural heart disease sinus VV'
      alternans triplets on NF EGM is independently associated with nonarrhythmic
      death, rather than with FVT/VF.

PMID- 25752991
TI  - Wafer-level hysteresis-free resonant carbon nanotube transistors.
AB  - We report wafer-level fabrication of resonant-body carbon nanotube (CNT) field
      effect transistors (FETs) in a dual-gate configuration. An integration density of
      >10(6) CNTFETs/cm(2), an assembly yield of >80%, and nanoprecision have been
      simultaneously obtained. Through combined chemical and thermal treatments,
      hysteresis-free (in vacuum) suspended-body CNTFETs have been demonstrated.
      Electrostatic actuation by lateral gate and FET-based readout of mechanical
      resonance have been achieved at room temperature. Both upward and downward in
      situ frequency tuning has been experimentally demonstrated in the dual-gate
      architecture. The minuscule mass, high resonance frequency, and in situ
      tunability of the resonant CNTFETs offer promising features for applications in
      radio frequency signal processing and ultrasensitive sensing. 

PMID- 25752992
TI  - The need for minimization strategies: current problems of immunosuppression.
AB  - New immunosuppressants and the better use of immunosuppressant combination
      therapy have led to significant improvements in renal allograft outcomes over the
      last decades. Yet, despite dramatic reduction in rejection rates and improvement
      in 1-year graft survival, long-term graft attrition rates remained rather
      constant. Current immunosuppressant combinations are frequently leading to
      overimmunosuppression and are increasing cardiovascular risk. Importantly,
      calcineurin inhibitors are nephrotoxic, contribute to cardiovascular risk and
      chronic allograft dysfunction. Furthermore, immunosuppressant-associated
      toxicities aggravate immune-mediated nephron injury and side effects lead to
      nonadherence, an identified important reason for late acute and chronic antibody
      mediated rejections. The frequent development of a chronic humoral response
      indicates rather insufficient immunosuppression of current combinations than
      simple under-immunosuppression. While there is no evidence that increasing
      immunosuppressive doses will improve outcomes or reduce de novo HLA-antibody
      formation, there is clear evidence that adequate minimization strategies will
      reduce side effect burden. Because of low rejection risk, but frequent side
      effects, drug minimization is particularly relevant for the many maintenance
      patients. In summary, new therapeutic strategies need to be developed from
      adequately powered clinical trials for reduction of the many side effects of
      immunosuppressants. Such evidence-based and time-dependent immunosuppressive
      minimization strategies are needed to achieve better long-term outcomes in the
      future. 

PMID- 25752993
TI  - Burden of focal cryoablation versus brachytherapy versus active surveillance in
      the treatment of very low-risk prostate cancer: a preliminary head-to-head
      comprehensive assessment.
AB  - Focal cryoablation (FC), brachytherapy (B) and active surveillance (AS) were
      offered to patients diagnosed with very low-risk prostate cancer (VLRPC) in an
      equal access protocol. Comprehensive validated self-report questionnaires
      accessed patients' erectile (IIEF-5) and voiding (IPSS) functions, Beck scales
      measured anxiety (BAI), hopelessness (BHS) and depression (BDI), SF-36 reflected
      patients' quality of life added to the emotional thermometers including five
      visual analogue scales (distress, anxiety, depression, anger and need for help).
      Kruskal-Wallis or ANOVA tests and Spearman's correlations were obtained among
      groups and studied variables. Thirty patients were included, median follow-up 18
      months (15-21). Those on AS (n = 11) were older, presented higher hopelessness
      (BHS) and lower general health perceptions (SF-36) scores than patients opting
      for FC (n = 10) and B (n = 9), P = 0.0014, P = 0.0268 and P = 0.0168
      respectively. Patients on B had higher IPSS scores compared to those under FC and
      AC, P = 0.0223. For all 30 included patients, Spearman's correlation (rs ) was
      very strong between BHS and general health perceptions (rs  = -0.800, P <
      0.0001), and weak/moderate between age and BHS (rs  = 0.405, P = 0.026) and age
      and general health perceptions (rs  = -0.564, P = 0.001). The sample power was
      >60%. To be considered in patients' counselling and care, current study supports
      the hypothesis that even VLRPC when untreated undermines psychosocial domains. 

PMID- 25752994
TI  - Maintenance and genetic load of plasmid pKON1 of Paracoccus kondratievae,
      containing a highly efficient toxin-antitoxin module of the hipAB family.
AB  - Paracoccus kondratievae NCIMB 13773(T), isolated from the maize rhizosphere,
      carries a large (95,049 bp) plasmid pKON1, whose structure has been significantly
      influenced by transposition. Almost 30% of the plasmid genome is composed of
      complete or truncated insertion sequences (ISs), representing seven IS families.
      The ISs are accompanied by numerous genes and gene clusters commonly found in
      bacterial chromosomes, encoding, among others, (i) a putative type III secretion
      system of the Rhizobiales-T3SS family, (ii) a type I restriction-modification
      system associated with the anti-codon nuclease (ACNase) gene prrC and (iii) OstA
      and OstB proteins involved in trehalose synthesis. The backbone of pKON1 is
      composed of replication and partitioning modules conserved in several large
      alphaproteobacterial replicons, including secondary chromid pAMI6 of Paracoccus
      aminophilus JCM 7686 and chromosome 2 (chromid) of Rhodobacter sphaeroides 2.4.1.
      pKON1 also contains a toxin-antitoxin system of the hipAB family, whose presence
      precludes removal of the plasmid from bacterial cells. This system, unlike two
      other related hipAB-family loci originating from plasmid pAMI8 and the chromosome
      of Paracoccus aminophilus JCM 7686, is highly efficient and permits very stable
      maintenance of a heterologous replicon in various hosts.

PMID- 25752995
TI  - Case Study: Community Engagement and Clinical Trial Success: Outreach to African
      American Women.
AB  - This brief report examines how the use of community engagement principles and
      approaches enhanced clinical trial recruitment and retention. The Community
      Engaged Research Core (CERC), a CTSA-supported resource designed to facilitate
      community involvement in clinical and translational research, was consulted to
      provide assistance with the implementation of the clinical trial, and
      specifically to enhance participation of the target population-African American
      women. CERC's key recommendations included: (1) convene a Community Engagement
      Studio, (2) redesign the recruitment advertisement, (3) simplify the language
      used to explain the scope of the study, and (4) provide transportation for
      participants. As a result of these interventions, a comprehensive strategy to
      recruit, enroll, and retain participants was formulated. After implementation of
      the plan by the study team, enrollment increased 78% and recruitment goals were
      met 16 months ahead of schedule. Participant retention and study drug adherence
      was 100%. We conclude that community engagement is essential to the development
      of an effective multifaceted plan to improve recruitment of underrepresented
      groups in clinical trials. 

PMID- 25752997
TI  - HIN-1: a New Epigenetic Biomarker Crucial for Therapy Selection in Glioblastoma
      Multiforme.
AB  - Glioblastoma multiforme (GBM) is the most common brain tumor in adults. The role
      of high in normal-1 (HIN-1) as a potential biomarker in combating this disease is
      being described for the first time in this study. A combination of O6
      methylguanine DNA methyltransferase (MGMT) and HIN-1 methylation could be a
      possible biomarker in therapy choice. Interestingly, survival data shows a
      similar trend for the methylation of MGMT and for unmethylation of HIN-1 and vice
      versa. Eighty-eight paraffin-embedded brain tumors were analyzed to screen
      methylation rates of different genes and evaluate the association between genes
      methylation and clinicopathologic variables. Our study is the first of its kind
      to indicate that MGMT and HIN-1 methylation status are inverted (97.7% of
      methylated ones) and could be new markers in the study of GBM prognosis,
      especially in the therapy selection.

PMID- 25752999
TI  - MYH9-related thrombocytopenia and intracranial bleedings: a complex
      clinical/surgical management and review of the literature.

PMID- 25752998
TI  - Inhibitor of Aurora Kinase B Induces Differentially Cell Death and Polyploidy via
      DNA Damage Response Pathways in Neurological Malignancy: Shedding New Light on
      the Challenge of Resistance to AZD1152-HQPA.
AB  - Aurora kinase B (AURKB), a crucial regulator of malignant mitosis, is involved in
      chromosome segregation and cytokinesis. AZD1152-HQPA is a selective inhibitor for
      AURKB activity and currently bears clinical assessment for several malignancies.
      However, the effect of this drug still needs to be elucidated in neurological
      malignancies. In this study, we investigated the restrictive potentials of
      AZD1152-HQPA in U87MG and SK-N-MC. AZD1152-HQPA treatment resulted in growth
      arrest, modification of cell cycle, and inhibition of colony formation in both
      cell lines. Furthermore, lower concentrations of AZD1152-HQPA profoundly induced
      apoptosis in U87GM (p53/p73 wild type) cells in parallel with an upregulation of
      p53 and its target genes BAX, BAD, APAF1, and PUMA. But remarkably, SK-N-MC
      (p53/p73 double null) responded to AZD1152-HQPA at much higher concentrations
      with an upregulation of genes involved in cell cycle progression, induction of
      excessive endoreduplication, and polyploidy rather than apoptosis. Although SK-N
      MC was resistant to AZD1152-HQPA, we did not find a mutation in the coding
      sequence of Aurora B gene or overexpressions of ABCG2 and ABCB1 as reported
      previously to be resistance mechanisms. However, our results suggest that p53/p73
      status could be an important mechanism for the type of response and resistance of
      the tumor cells to AZD1152-HQPA. Collectively, inhibition of Aurora kinase B
      differentially induced cell death and polyploidy via DNA damage response
      pathways, depending on the status of p53/p73. We suggest p53/p73 could be a key
      regulator of sensitivity to AZD1152-HQPA and their status should be explored in
      clinical response to this ongoing drug in clinical trials. 

PMID- 25753000
TI  - Novel score for prediction of malignant bile duct obstruction based on
      biochemical and clinical markers.
AB  - BACKGROUND: Early differentiation of malignant from benign bile duct obstruction
      is of utmost importance. AIM: To identify biochemical and clinical predictors for
      malignancy in patients with bile duct obstruction, and establish a predictive
      model by combining pre-treatment patient characteristics. A web-based application
      was developed for easy assessment of malignant bile duct probability (www.pmal
      score.org). METHODS: One thousand hundred and thirty-five patients [median age 66
      (52-75) years, 53% male] with bile duct obstruction of various aetiologies were
      retrospectively evaluated at our tertiary referral centre. Multivariate logistic
      regression analysis identified factors as independently significant for malignant
      bile duct obstruction. A predictive risk score was established using ROC analysis
      and applied to an external validation cohort of 101 patients. RESULTS: Three
      hundred and ninety-four patients had malignant bile duct obstruction proven by
      surgery, while in 741 patients benign obstruction was observed. Multivariate
      analysis identified various clinical factors to be predictive for malignancy. On
      the basis of eight predictors, a risk score for malignancy was developed [X =
      0.025 * [age] + 1.239 * [1 if weight loss, otherwise 0] - 0.235 * [1 if pain,
      otherwise 0] + 0.649 * [1 if diabetes, otherwise 0] + 0.896 * [1 if jaundice,
      otherwise 0] + 0.109 * [bilirubin] + 0.0007 * [gamma-GT] + 0.0003 * [AP] -
      4.374]: A significant correlation between the predicted malignancy and the actual
      malignancy was found by ROC (AUC: 0.862; 95% CI 0.838-0.886, P < 0.0001).
      CONCLUSIONS: This predictive risk score estimates the risk of malignancy in
      patients with bile duct obstruction, and it seems to be very accurate. A better
      prediction enables both earlier diagnosis of malignant obstructive disease and
      improved management of patients with bile duct obstruction, which may result in
      reduced morbidity and mortality.

PMID- 25753002
TI  - Novel anti-melanogenic hexapeptoids, PAL-10 and PAL-12.
AB  - Diverse compound sources are being explored for de-pigmentation activities to
      develop novel therapeutic agents or functional cosmetic ingredients for hyper
      pigmentation disorders. Peptoids are a class of peptidomimetics whose side chains
      are appended to the nitrogen atom of the peptide backbone, instead of alpha
      carbon. Peptoids are more durable against proteolysis and are being actively
      investigated in drug discovery, but rarely studied as cosmetic ingredients. Here,
      we demonstrated that new hexa-peptoids, PAL-10 and PAL-12, can inhibit
      melanogenesis in B16F10 melanoma cells, a 3D pigmented human skin model
      (Neoderm((r))-ME, Tegoscience Co) and zebrafish. Anti-melanogenic effects of PAL
      10 or PAL-12 as compared with arbutin, a positive control in B16F10 cells,
      Neoderm((r))-ME and zebrafish were statistically significant and concentration
      dependent anti-melanogenic effects were manifested as determined by image,
      histology, and melanin contents. Anti-melanogenic effects of PAL-10 appeared to
      be from enzymatic inhibition of tyrosinase while mRNA expression of melanogenic
      enzymes was not affected. In conclusion, we demonstrated that PAL-10 and PAL-12
      can be used as a new cosmetic ingredient with strong brightening efficacies. 

PMID- 25753001
TI  - A Protein Interaction between beta-Catenin and Dnmt1 Regulates Wnt Signaling and
      DNA Methylation in Colorectal Cancer Cells.
AB  - Aberrant activation of the Wnt signaling pathway is an important step in the
      initiation and progression of tumor development in diverse cancers. The central
      effector of canonical Wnt signaling, beta-catenin (CTNNB1), is a multifunctional
      protein, and has been extensively studied with respect to its roles in cell-cell
      adhesion and in regulation of Wnt-driven transcription. Here, a novel mass
      spectrometry-based proteomics technique in colorectal cancer cells expressing
      stabilized beta-catenin, was used to identify a protein-protein interaction
      between beta-catenin and DNA methyltransferase I (Dnmt1) protein, the primary
      regulator of DNA methylation patterns in mammalian cells. Dnmt1 and beta-catenin
      strongly colocalized in the nuclei of colorectal cancer cells, and the
      interaction is mediated by the central domain of the Dnmt1 protein. Dnmt1 protein
      abundance is dependent upon the levels of beta-catenin, and is increased in cells
      expressing stabilized mutant beta-catenin. Conversely, the Dnmt1 regulates the
      levels of nuclear beta-catenin and beta-catenin/TCF-driven transcription. In
      addition, lysine-specific demethylase 1 (LSD1/KDM1A), a regulator of DNMT1
      stability, was identified as a component of the Dnmt1-beta-catenin protein
      complex and perturbation of the Dnmt1-beta-catenin interaction altered DNA
      methylation. In summary, a functional protein-protein interaction was identified
      between two critically important oncoproteins, in turn revealing a link between
      Wnt signaling and downstream nuclear functions mediated by Dnmt1. IMPLICATIONS:
      Two critical oncoproteins, Dnmt1 and beta-catenin, mutually regulate one each
      other's levels and activities in colorectal cancer cells.

PMID- 25753003
TI  - Non-drug-induced Stevens-Johnson syndrome successfully treated with high-dose
      i.v. immunoglobulin.

PMID- 25753004
TI  - The effect of C1 bursting fracture on comparative anatomical relationship between
      the internal carotid artery and the atlas.
AB  - PURPOSE: To describe the effect of the C1 bursting fracture on the location of
      the internal carotid artery (ICA) around the atlas. METHODS: The authors analyzed
      the morphology of the atlas and the ICA in 15 patients with C1 bursting fracture
      and compared with control group (77 patients) without any pathology. All patients
      were evaluated with CT angiography for the anatomical assessment. The laterality
      of the ICA, the distances of the ICA from the midline, anterior tubercle, and
      ventral surface of the C1 lateral mass were compared between two groups. The
      distance between the lateral margin of the longus capitis muscle and the inner
      edge of the transverse foramen was also measured. RESULTS: Medially located ICA
      was more common in the C1 bursting fracture group than control group (76.7 vs
      42.8 %). There were no significant differences between 2 groups for the distance
      from the midline, anterior tubercle, and ventral surface of the C1 lateral mass,
      respectively. The distance of the longus capitis muscle to transverse foramen was
      2.52 +/- 2.09 and 4.15 +/- 3.09 mm in each group, and there was statistically
      significant difference (p < 0.01). CONCLUSIONS: Lateral displacement of the bony
      structure of C1 bursting fracture changes the relative location of the ICA
      medially, which increase the injury risk during the bicortical C1 screw
      insertion. These data suggest that CT angiography or enhanced CT scans can give
      critical information to choose the ideal fixation technique and the proper
      trajectory of the screws for C1 bursting fracture.

PMID- 25753005
TI  - Reliability and accuracy of ultrasound measurements with and without the aid of
      previous radiographs in adolescent idiopathic scoliosis (AIS).
AB  - PURPOSE: The objectives of this preliminary study were to assess the reliability
      and accuracy of ultrasound (US) for measuring coronal curvature with and without
      the aid of a previous radiograph, and to evaluate the ability of US to detect
      curve progression in adolescent idiopathic scoliosis (AIS) patients. METHODS:
      Four raters measured 20 AIS US images twice at one-week intervals. Intra-rater
      reliability and correlation with radiograph were investigated with (rater 1) and
      without (raters 2-4) the aid of a previous radiograph. The center of lamina (COL)
      method was used to approximate the Cobb angle. RESULTS: Thirty-six curves were
      identified. All raters showed high intra-rater reliability (ICC[2,1] >0.80). With
      the aid of a previous radiograph, rater 1 showed higher correlation with
      radiograph (ICC[2,1] = 0.86), better standard error of measurement (SEM = 2.2
      degrees ), and improved error index of selecting end-vertebrae (EI = 1.34), but
      no statistical improvement of intra-rater reliability (p > 0.05). For rater 2-4,
      the range of the ICC[2,1] values between US and radiograph measurements, the SEM
      value, and the range of the EI values were 0.70 degrees -0.72 degrees , 3.3
      degrees , and 1.65 degrees -2.36 degrees , respectively. Specificity and
      sensitivity of US for detecting curve progression were 0.91 and 0.83,
      respectively. CONCLUSIONS: Using a previous radiograph as a measurement aid
      helped the user to measure coronal curvature from US images, and improved the
      accuracy of end-vertebrae selection. US showed high sensitivity and specificity
      for detecting curve progression, indicating that US may be a suitable, radiation
      free alternative for monitoring patients with AIS who have mild or moderate
      curves.

PMID- 25753006
TI  - Using the modified Delphi method to establish a new Chinese clinical consensus of
      the treatments for cervical radiculopathy.
AB  - PURPOSE: Although cervical radiculopathy is very common, there is no standard
      treatment for this condition, with little high-level evidence available to guide
      the treatment choice. Thus, this study aimed to review the current data on the
      management of cervical radiculopathy; and, further, to establish a new Chinese
      clinical consensus of the treatments for cervical radiculopathy using the Delphi
      method. METHODS: First, a systematic review of the previously established
      treatment guidelines and of articles related to cervical radiculopathy was
      conducted to establish a protocol for the clinical consensus of the treatment for
      cervical radiculopathy. Second, from February 2012 to June 2014, we performed a
      modified Delphi survey in which the current professional opinions from 30
      experienced experts, representing almost all of the Chinese provinces, were
      gathered. Three rounds were performed, and consensus was defined as >=70%
      agreement. RESULTS: Consensus of the treatments for cervical radiculopathy was
      reached on seven aspects, including the proportion of patients requiring only non
      surgical therapies; the effectiveness of neck immobilization, physiotherapy,
      pharmacologic treatment; surgical indications; contraindications; surgery.
      CONCLUSIONS: The modified Delphi study conducted herein reached a consensus
      concerning several treatment issues for cervical radiculopathy. In the absence of
      high-level evidence, at present, these expert opinion findings will help guide
      health care providers to define the appropriate treatment in their regions. Items
      with no consensus provide excellent areas for future research.

PMID- 25753007
TI  - High-heeled-related alterations in the static sagittal profile of the spino
      pelvic structure in young women.
AB  - PURPOSE: Women wearing high-heeled shoes have been considered to be more
      characterizing beauty, self-assurance and elegance. However, while maintaining
      the body on this type of support base, women with increased heel height often
      complain that wearing high-heeled shoes causes them to experience low back pain.
      The aim of the present study was to morphologically assess the effect of high
      heel use on the static sagittal profile of the spino-pelvic structure. METHODS: A
      total of 21 Chinese girls were recruited in this study, with informed written
      consent. For each participant, standing left lateral radiographs, including that
      of the spine and pelvis, were obtained in a standardized standing position under
      barefoot and high-heel use conditions. The radiographic assessments were
      performed to detect the changes in the spino-pelvic profile under barefoot and
      high-heel use conditions. RESULTS: The average lumbar lordosis (LL) was 54.3 +/-
      6.4o under the barefoot condition and increased to 65.2 +/- 5.1o after high-heel
      use (P < 0.001), with a significant increase in the disc L5/S1 and disc L4/L5
      tilt angles. Of the 21 participants, 15 (71.43 %) had an increased kyphosis value
      for thoracic kyphosis, and 6 (28.57 %) had a decreased value after high-heel use,
      with a significant increased mean kyphosis value of 3.4 +/- 1.5o overall (P <
      0.001). The sagittal vertical axis (SVA) was always positive and was worse after
      high-heel use (P = 0.012): 11.5 +/- 8.7 mm under the barefoot condition and 29.8
      +/- 8.5 mm under the high-heel use condition. Bivariate correlation analysis
      showed that both DeltaLL and DeltaSVA were positively associated with the heel
      height of the shoes and were inversely associated with the age of the
      participants. Receiver operator characteristic analysis showed that a heel height
      >45.5 mm was strongly predictive of the loss of static sagittal balance of the
      spine during high-heel use (sensitivity 87.5 %, specificity 62.5 %, area under
      the curve: 0.773; P = 0.026). CONCLUSIONS: The present study revealed that
      wearing high-heeled shoes can lead to increased LL and an uneconomic body
      position. This finding may help explain why some women complain that wearing high
      heeled shoes causes them to experience low back pain.

PMID- 25753008
TI  - Fatal reactivation of hepatitis B virus infection in a patient with adult T-cell
      leukemia-lymphoma receiving the anti-CC chemokine receptor 4 antibody
      mogamulizumab.
AB  - We report an adult T-cell leukemia-lymphoma (ATL) patient suffering from fatal
      reactivation of hepatitis B virus (HBV) infection after treatment with the anti
      CC chemokine receptor 4 (CCR4) monoclonal antibody, mogamulizumab. HBV
      reactivation occurred without liver damage in this hepatitis B surface antigen
      (HBsAg) negative patient, who was seropositive for antibodies against the viral
      core and surface antigens at baseline, after two cycles of CHOP regimen
      (cyclophosphamide, doxorubicin, vincristine and prednisolone) followed by six
      cycles of THP-COP regimen (cyclophosphamide, pirarubicin, vincristine and
      prednisolone). Unexpectedly, mogamulizumab monotherapy for relapsed CCR4 positive
      ATL induced sudden and fatal liver failure due to HBV reactivation, despite
      antiviral prophylaxis with entecavir. This clinical course may not only offer
      important suggestions to prevent critical HBV reactivation in HBsAg positive
      cancer patients who receive immune-enhancing drugs such as anti-CCR4 antibody,
      but also provide a clue to understanding the pathogenesis of HBV reactivation
      following systemic chemotherapy. 

PMID- 25753009
TI  - eHealth interventions for the prevention and treatment of overweight and obesity
      in adults: a systematic review with meta-analysis.
AB  - A systematic review of randomized controlled trials was conducted to evaluate the
      effectiveness of eHealth interventions for the prevention and treatment of
      overweight and obesity in adults. Eight databases were searched for studies
      published in English from 1995 to 17 September 2014. Eighty-four studies were
      included, with 183 intervention arms, of which 76% (n = 139) included an eHealth
      component. Sixty-one studies had the primary aim of weight loss, 10 weight loss
      maintenance, eight weight gain prevention, and five weight loss and maintenance.
      eHealth interventions were predominantly delivered using the Internet, but also
      email, text messages, monitoring devices, mobile applications, computer programs,
      podcasts and personal digital assistants. Forty percent (n = 55) of interventions
      used more than one type of technology, and 43.2% (n = 60) were delivered solely
      using eHealth technologies. Meta-analyses demonstrated significantly greater
      weight loss (kg) in eHealth weight loss interventions compared with control (MD 
      2.70 [-3.33,-2.08], P < 0.001) or minimal interventions (MD -1.40 [-1.98,-0.82],
      P < 0.001), and in eHealth weight loss interventions with extra components or
      technologies (MD 1.46 [0.80, 2.13], P < 0.001) compared with standard eHealth
      programmes. The findings support the use of eHealth interventions as a treatment
      option for obesity, but there is insufficient evidence for the effectiveness of
      eHealth interventions for weight loss maintenance or weight gain prevention. 

PMID- 25753012
TI  - Long-term follow-up of STAT5B deficiency in three argentinian patients: clinical
      and immunological features.
AB  - The signal transducer and activator of transcription (STAT) family of proteins
      regulate gene transcription in response to a variety of cytokines. STAT5B, in
      particular, plays an important role in T cells, where it is a key mediator of
      interleukin-2 (IL-2) induced responses. STAT5B deficiency causes a rare autosomal
      recessive disorder reported in only a handful of individuals. There are currently
      ten published cases of STAT5B deficiency, four of which are Argentinians. AIM:
      This is a report of more than 10 years follow up of the clinical and
      immunological features of three Argentinian STAT5B deficient patients.
      CONCLUSION: More than a decade of follow-up demonstrates that STAT5B deficiency
      is associated with various clinical pathologies that cause significant morbidity.
      Early diagnosis is critical for the prevention and improvement of clinical
      outcomes for STAT5B deficient patients.

PMID- 25753013
TI  - Identification of hemoglobin variants by top-down mass spectrometry using
      selected diagnostic product ions.
AB  - Hemoglobin disorder diagnosis is a complex procedure combining several analytical
      steps. Due to the lack of specificity of the currently used protein analysis
      methods, the identification of uncommon hemoglobin variants (proteoforms) can
      become a hard task to accomplish. The aim of this work was to develop a mass
      spectrometry-based approach to quickly identify mutated protein sequences within
      globin chain variants. To reach this goal, a top-down electron transfer
      dissociation mass spectrometry method was developed for hemoglobin beta chain
      analysis. A diagnostic product ion list was established with a color code
      strategy allowing to quickly and specifically localize a mutation in the
      hemoglobin beta chain sequence. The method was applied to the analysis of rare
      hemoglobin beta chain variants and an (A)gamma-beta fusion protein. The results
      showed that the developed data analysis process allows fast and reliable
      interpretation of top-down electron transfer dissociation mass spectra by
      nonexpert users in the clinical area. 

PMID- 25753014
TI  - Vibrational algorithms for quantitative crystallographic analyses of
      hydroxyapatite-based biomaterials: II, application to decayed human teeth.
AB  - A systematic investigation, based on highly spectrally resolved Raman
      spectroscopy, was undertaken to research the efficacy of vibrational assessments
      in locating chemical and crystallographic fingerprints for the characterization
      of dental caries and the early detection of non-cavitated carious lesions. Raman
      results published by other authors have indicated possible approaches for this
      method. However, they conspicuously lacked physical insight at the molecular
      scale and, thus, the rigor necessary to prove the efficacy of this spectroscopy
      method. After solving basic physical challenges in a companion paper, we apply
      them here in the form of newly developed Raman algorithms for practical dental
      research. Relevant differences in mineral crystallite (average) orientation and
      texture distribution were revealed for diseased enamel at different stages
      compared with healthy mineralized enamel. Clear spectroscopy features could be
      directly translated in terms of a rigorous and quantitative classification of
      crystallography and chemical characteristics of diseased enamel structures. The
      Raman procedure enabled us to trace back otherwise invisible characteristics in
      early caries, in the translucent zone (i.e., the advancing front of the disease)
      and in the body of lesion of cavitated caries. 

PMID- 25753015
TI  - Multi-color reflectance imaging of middle ear pathology in vivo.
AB  - Otoscopic examination using white-light illumination has remained virtually
      unchanged for well over a century. However, the limited contrast of white-light
      otoscopy constrains the ability to make accurate assessment of middle ear
      pathology and is subject to significant observer variability. Here, we employ a
      modified otoscope with multi-color imaging capabilities for superior
      characterization of the middle ear constituents in vivo and for enhanced
      diagnosis of acute otitis media and cholesteatoma. In this pilot study, five
      patients undergoing surgery for tympanostomy tube placement and congenital
      cholesteatoma excision were imaged using the custom-designed multi-color video
      rate reflectance imaging system. We show that the multi-color imaging approach
      offers an increase in image contrast, thereby enabling clear visualization of the
      middle ear constituents, especially of the tympanic membrane vascularity.
      Differential absorption at the multiple wavelengths provides a measure of
      biochemical and morphological information, and the rapid acquisition and analysis
      of these images aids in objective evaluation of the middle ear pathology. Our
      pilot study shows the potential of using label-free narrow-band reflectance
      imaging to differentiate middle ear pathological conditions from normal middle
      ear. This technique can aid in obtaining objective and reproducible diagnoses as
      well as provide assistance in guiding excisional procedures. 

PMID- 25753016
TI  - In vivo validation of the in silico predicted pressure drop across an
      arteriovenous fistula.
AB  - The creation of an arteriovenous fistula offers a unique example of vascular
      remodelling and adaption. Yet, the specific factors which elicit remodelling
      events which determine successful maturation or failure have not been
      unambiguously determined. Computational fluid dynamic (CFD) simulations are
      increasingly been employed to investigate the interaction between local
      hemodynamics and remodelling and can potentially be used to assist in clinical
      risk assessment of maturation or failure. However, these simulations are
      inextricably linked to their prescribed boundary conditions and are reliant on in
      vivo measurements of flow and pressure to ensure their validity. The study
      compares in vivo measurements of the pressure distribution across arteriovenous
      fistulae against a representative numerical model. The results of the study
      indicate relative agreement (error ~ 8-10%) between the in vivo and CFD
      prediction of the mean pressure drop across the AVFs. The large pressure drop
      across the AVFs coincided with a palpable thrill (perivascular vibration) in vivo
      and fluctuations were observed in the numerical pressure drop signal due to flow
      instabilities arising at the anastomosis. This study provides a benchmark of the
      pressure distribution within an AVF and validates that CFD solutions are capable
      of replicating the abnormal physiological flow conditions induced by fistula
      creation. 

PMID- 25753017
TI  - Synthetic mimics of the extracellular matrix: how simple is complex enough?
AB  - Cells reside in a complex and dynamic extracellular matrix where they interact
      with a myriad of biophysical and biochemical cues that direct their function and
      regulate tissue homeostasis, wound repair, and even pathophysiological events.
      There is a desire in the biomaterials community to develop synthetic hydrogels to
      recapitulate facets of the ECM for in vitro culture platforms and tissue
      engineering applications. Advances in synthetic hydrogel design and chemistries,
      including user-tunable platforms, have broadened the field's understanding of the
      role of matrix cues in directing cellular processes and enabled the design of
      improved tissue engineering scaffolds. This review focuses on recent advances in
      the development and fabrication of hydrogels and discusses what aspects of ECM
      signals can be incorporated to direct cell function in different contexts.

PMID- 25753018
TI  - Nicotinamide phosphoribosyltransferase facilitates post-stroke angiogenesis.

PMID- 25753019
TI  - A multicenter study on the performance of a fully automated, walk-away high
      throughput analyzer for pretransfusion testing in the US population.
AB  - BACKGROUND: Moving to automation is a major focus of transfusion centers. Erytra
      (Grifols) is a walk-away analyzer with high-performance and -throughput capacity
      for pretransfusion testing. Efficiency and performance of Erytra with its cards
      and reagents were evaluated in comparison to Food and Drug Administration (FDA)
      approved reference methods. STUDY DESIGN AND METHODS: A total of 5279 blood
      samples (46% patients; 54% donors) were obtained from US blood establishment
      facilities. Samples were analyzed with Erytra and results were compared with the
      routine FDA-licensed automated platforms used by the clinical study sites. A
      total of 25,217 tests were performed (15,322 ABO/D/reverse typing; 4916 Rh
      phenotypes, 669 K typing, 838 antibody screens, 759 antibody identifications, 250
      cross-matches, 244 ABO compatibilities by immediate-spin cross-match, and 219
      direct antiglobulin tests [DATs]). RESULTS: Global agreement between Erytra and
      the comparison platforms was 99.66%, with 99.82% positive percent agreement (95%
      lower confidence bound [LCB], 99.75%) and 99.50% negative percent agreement (95%
      LCB, 99.37%). There were 85 discrepancies (0.34%), including cross-matches (n =
      13), antibody screens (n = 10), antibody identifications (n = 21), and DATs (n =
      5), whereas an excellent concordance was obtained in blood grouping
      determinations (ABO/D/C/E/c/e/K, 0.04%-0.22% discrepancies). Analysis of the
      discrepancies showed that Erytra provided the correct result in 51 of them (60%),
      with only five false negatives (one O patient transplanted with A, one mixed
      field reaction in a very weak D, one anti-Vel, two A2rr). Erytra results were
      100% reproducible in a series of 3760 repetition tests. CONCLUSION: Grifols'
      Erytra analyzer showed reliable efficacy compared with equivalent FDA-licensed
      reagents and FDA-cleared instruments.

PMID- 25753020
TI  - Should we offer screening for hepatitis B and other infections to immigrants-
      legal or illegal?

PMID- 25753021
TI  - Evaluating typhoid vaccine effectiveness in travelers' vaccination.

PMID- 25753023
TI  - Relationship between subjective halitosis and psychological factors.
AB  - OBJECTIVES: Subjective halitosis is a growing concern in the fields of dentistry
      and psychology. This study was designed to determine the association between
      subjective halitosis and contributing psychological factors. METHODS: Data for
      this cross-sectional study were gathered from 4,763 participants who had answered
      questions on subjective halitosis and psychological factors (depression, anxiety,
      stress and personality traits) in the study on the epidemiology of psychological,
      alimentary health and nutrition (SEPAHAN). Binary logistic regression was used
      for data analysis. RESULT: The mean age of all subjects was 36.58 years; and the
      majority of subjects were female (55.8%), married (81.2%) and graduates (57.2%).
      The prevalence of subjective halitosis was 52.8%. The majority of subjects with
      the complaint of subjective halitosis were married (P<0.001) and young (P=0.07).
      Participants with subjective halitosis were significantly more anxious [odds
      ratio (OR)=1.76, 95% confidence interval (95% CI): 1.38-2.24], stressed (OR=1.41,
      95% CI: 1.17-1.71) and depressed (OR=1.31, 95% CI: 1.09-1.57). Among personality
      traits, neuroticism was a risk factor (tertile 1 vs. tertile 2: OR=1.29, 95% CI:
      1.09-1.51; and tertile 1 vs. tertile 3: OR=1.74, 95% CI: 1.43-2.13) and
      conscientiousness was revealed to be a protective factor (tertile 1 vs. tertile
      2: OR=0.82, 95% CI: 0.70-0.98; and tertile 1 vs. tertile 3: OR=0.65, 95% CI: 0.53
      0.80). CONCLUSION: It seems that psychological factors, such as anxiety,
      depression and stress, as well as some personality traits, can be considered as
      risk factors for subjective halitosis. Multidisciplinary efforts by dental and
      psychological professionals must be considered to address this problem.

PMID- 25753024
TI  - Erratum to: Correlates of HIV testing among African American and Latino Church
      congregants: the role of HIV stigmatizing attitudes and discussions about HIV.

PMID- 25753025
TI  - Dentists' use of behavioural management techniques and their attitudes towards
      treating paediatric patients with dental anxiety.
AB  - PURPOSE: The purpose of this study was to explore the relationship between
      dentists' education in treatment of dental anxiety (DA), dentists' attitudes
      towards patients with DA and dentists' use of BMT. METHODS: An anonymous
      questionnaire was sent electronically to 611 dentists in the Public Dental
      Service in Norway. Statistical evaluation was done using cross tabulation with
      Chi square and logistic regression analyses. RESULTS: The response rate was 65 %
      (n = 391). About half of the respondents (53 %, n = 208) had followed
      postgraduate courses in treating patients with DA. The following were the most
      common attitudes towards treating young patients with DA: it feels like making a
      contribution (72 %, n = 286), it is difficult or tiresome (54 %, n = 215) and it
      is a positive challenge (51 %, n = 203). Dentists who had taken postgraduate
      courses in DA more often reported anxious patients as a positive challenge (60
      vs. 42 %, p < 0.001) and were less reluctant to treat these patients (5 vs. 15 %,
      p = 0.002). The most frequently used BMT was tell-show-do (87 %, n = 340),
      followed by relaxation (35 %, n = 132), distraction (25 %, n = 94), systematic
      cognitive behaviour therapy (22 %, n = 84) and conscious sedation (18 %, n = 69).
      Dentists without postgraduate courses in DA used fewer techniques when treating
      these patients (OR 2.1, 95 % CI 1.3-3.3, p = 0.001) compared with dentists who
      had taken these courses. CONCLUSION: Country of graduation and postgraduate
      courses in DA had a strong relationship with dentists' use of BMT and dentists'
      attitudes towards young patients with DA.

PMID- 25753026
TI  - Compensatory intracranial arterial dilatation in extracranial carotid
      atherosclerosis: the Northern Manhattan study.
AB  - BACKGROUND: There is a scarcity of data supporting the association between
      atherosclerosis and dolichoectasia in unbiased samples. AIMS: To test the
      hypothesis that the association between dolichoectasia and extracranial carotid
      atherosclerosis depends on the degree of collateral circulation. METHODS: The
      Northern Manhattan Study magnetic resonance imaging substudy consists of 1290
      participants who remained stroke-free at the time of magnetic resonance imaging.
      Arterial diameters were collected in all participants with available magnetic
      resonance angiography. Dolichoectasia was defined as a head-size adjusted
      diameter >2 standard deviation for each artery. Carotid Doppler was used to
      evaluate for carotid atherosclerosis (carotid plaque, maximum plaque thickness
      and carotid intima media thickness). RESULTS: We included 994 participants with
      available Doppler and magnetic resonance angiography data (mean age 63 years, 60%
      female). Any dolichoectasia was reported in 16% of participants, 54% had at least
      one carotid plaque and the mean carotid intima media thickness was 0.92 +/- 0.09
      mm. After adjusting for demographic and clinical characteristics, there was no
      association between markers of carotid atherosclerosis and dolichoectasia.
      However, stratifying by collaterals, it was observed that dolichoectasia was more
      likely in the anterior and posterior circulations when collaterals were available
      among participants with carotid atherosclerosis. These associations were
      confirmed by noting an increment in arterial diameters in the corresponding
      arteries ipsilateral and contralateral to each carotid as well as in the
      posterior circulation. CONCLUSIONS: We did not find an association of
      extracranial carotid atherosclerosis with dolichoectasia. However, we found that
      dolichoectasia is more frequent when intracranial collaterals are available
      suggesting a compensatory process that needs further investigation.

PMID- 25753027
TI  - Medicinal species with gastroprotective activity found in the Brazilian Cerrado.
AB  - Peptic and/or duodenal ulcers are characterized by diverse acute and chronic
      ulcerative lesions that commonly arise in any portion of the gastric mucosa that
      is exposed to the aggressive action of gastric acid. The pathophysiology of
      peptic ulcers has been attributed to an imbalance between aggressive and
      protective factors. In Brazil, medicinal plants are commonly used to treat this
      ailment. A country with great biodiversity, Brazil is considered a rich source of
      therapeutic products. There have been popular and pharmacological reports on the
      medicinal relevance of the Brazilian cerrado plant species, including Ananas
      ananassoides, Celtis iguanaea, Encholirium spectabile, Hymenaea stigonocarpa,
      Lafoensia pacari, Qualea grandiflora, Qualea parvifora, Mouriri pusa, Solanum
      lycocarpum, Solanum paniculatum, Serjania erecta, and Vochysia tucanorum, in the
      treatment of stomach disorders. The aim of the present review was to report on
      some of the Brazilian cerrado plants that are used in folk medicine because of
      their gastroprotective potential and to encourage novel studies in the search and
      preservation of plants with this therapeutic potential. 

PMID- 25753028
TI  - Corticosterone primes the neuroinflammatory response to DFP in mice: potential
      animal model of Gulf War Illness.
AB  - Gulf War Illness (GWI) is a multi-symptom disorder with features characteristic
      of persistent sickness behavior. Among conditions encountered in the Gulf War
      (GW) theater were physiological stressors (e.g., heat/cold/physical
      activity/sleep deprivation), prophylactic treatment with the reversible AChE
      inhibitor, pyridostigmine bromide (PB), the insect repellent, N,N-diethyl-meta
      toluamide (DEET), and potentially the nerve agent, sarin. Prior exposure to the
      anti-inflammatory glucocorticoid, corticosterone (CORT), at levels associated
      with high physiological stress, can paradoxically prime the CNS to produce a
      robust proinflammatory response to neurotoxicants and systemic inflammation; such
      neuroinflammatory effects can be associated with sickness behavior. Here, we
      examined whether CORT primed the CNS to mount neuroinflammatory responses to GW
      exposures as a potential model of GWI. Male C57BL/6 mice were treated with
      chronic (14 days) PB/ DEET, subchronic (7-14 days) CORT, and acute exposure (day
      15) to diisopropyl fluorophosphate (DFP), a sarin surrogate and irreversible AChE
      inhibitor. DFP alone caused marked brain-wide neuroinflammation assessed by qPCR
      of tumor necrosis factor-alpha, IL6, chemokine (C-C motif) ligand 2, IL-1beta,
      leukemia inhibitory factor, and oncostatin M. Pre-treatment with high
      physiological levels of CORT greatly augmented (up to 300-fold) the
      neuroinflammatory responses to DFP. Anti-inflammatory pre-treatment with
      minocycline suppressed many proinflammatory responses to CORT+DFP. Our findings
      are suggestive of a possible critical, yet unrecognized interaction between the
      stressor/environment of the GW theater and agent exposure(s) unique to this war.
      Such exposures may in fact prime the CNS to amplify future neuroinflammatory
      responses to pathogens, injury, or toxicity. Such occurrences could potentially
      result in the prolonged episodes of sickness behavior observed in GWI. Gulf War
      (GW) veterans were exposed to stressors, prophylactic medicines and, potentially,
      nerve agents in theater. Subsequent development of GW Illness, a persistent multi
      symptom disorder with features characteristic of sickness behavior, may be caused
      by priming of the CNS resulting in exaggerated neuroinflammatory responses to
      pathogens/insults. Nerve agent, diisopropyl fluorophosphate (DFP), produced a
      neuroinflammatory response that was exacerbated by pre-treatment with levels of
      corticosterone simulating heightened stressor conditions. While prophylactic
      treatments reduced DFP-induced neuroinflammation, this effect was negated when
      those treatments were combined with corticosterone.

PMID- 25753029
TI  - Development and validation of the WASP classification system for optical
      diagnosis of adenomas, hyperplastic polyps and sessile serrated adenomas/polyps.
AB  - OBJECTIVE: Accurate endoscopic differentiation would enable to resect and discard
      small and diminutive colonic lesions, thereby increasing cost-efficiency. Current
      classification systems based on narrow band imaging (NBI), however, do not
      include neoplastic sessile serrated adenomas/polyps (SSA/Ps). We aimed to develop
      and validate a new classification system for endoscopic differentiation of
      adenomas, hyperplastic polyps and SSA/Ps <10 mm. DESIGN: We developed the
      Workgroup serrAted polypS and Polyposis (WASP) classification, combining the NBI
      International Colorectal Endoscopic classification and criteria for
      differentiation of SSA/Ps in a stepwise approach. Ten consultant
      gastroenterologists predicted polyp histology, including levels of confidence,
      based on the endoscopic aspect of 45 polyps, before and after participation in
      training in the WASP classification. After 6 months, the same endoscopists
      predicted polyp histology of a new set of 50 polyps, with a ratio of lesions
      comparable to daily practice. RESULTS: The accuracy of optical diagnosis was 0.63
      (95% CI 0.54 to 0.71) at baseline, which improved to 0.79 (95% CI 0.72 to 0.86,
      p<0.001) after training. For polyps diagnosed with high confidence the accuracy
      was 0.73 (95% CI 0.64 to 0.82), which improved to 0.87 (95% CI 0.80 to 0.95,
      p<0.01). The accuracy of optical diagnosis after 6 months was 0.76 (95% CI 0.72
      to 0.80), increasing to 0.84 (95% CI 0.81 to 0.88) considering high confidence
      diagnosis. The combined negative predictive value with high confidence of
      diminutive neoplastic lesions (adenomas and SSA/Ps together) was 0.91 (95% CI
      0.83 to 0.96). CONCLUSIONS: We developed and validated the first integrative
      classification method for endoscopic differentiation of small and diminutive
      adenomas, hyperplastic polyps and SSA/Ps. In a still image evaluation setting,
      introduction of the WASP classification significantly improved the accuracy of
      optical diagnosis overall as well as SSA/P in particular, which proved to be
      sustainable after 6 months.

PMID- 25753030
TI  - In healthy volunteers, immunohistochemistry supports squamous to columnar
      metaplasia as mechanism of expansion of cardia, aggravated by central obesity.
AB  - INTRODUCTION: Recently, we showed that the length of cardiac mucosa in healthy
      volunteers correlated with age and obesity. We have now examined the
      immunohistological characteristics of this expanded cardia to determine whether
      it may be due to columnar metaplasia of the distal oesophagus. METHODS: We used
      the squamocolumnar junction (SCJ), antral and body biopsies from the 52
      Helicobacter pylori-negative healthy volunteers who had participated in our
      earlier physiological study and did not have hiatus hernia, transsphincteric acid
      reflux, Barrett's oesophagus or intestinal metaplasia (IM) at cardia. The
      densities of inflammatory cells and reactive atypia were scored at squamous,
      cardiac and oxyntocardiac mucosa of SCJ, antrum and body. Slides were stained for
      caudal type homeobox 2 (CDX-2), villin, trefoil factor family 3 (TFF-3) and liver
      intestine (LI)-cadherin, mucin MUC1, Muc-2 and Muc-5ac. In addition, biopsies
      from 15 Barrett's patients with/without IM were stained and scored as comparison.
      Immunohistological characteristics were correlated with parameters of obesity and
      high-resolution pH metry recording. RESULTS: Cardiac mucosa had a similar
      intensity of inflammatory infiltrate to non-IM Barrett's and greater than any of
      the other upper GI mucosae. The immunostaining pattern of cardiac mucosa most
      closely resembled non-IM Barrett's showing only slightly weaker CDX-2
      immunostaining. In distal oesophageal squamous mucosa, expression of markers of
      columnar differentiation (TFF-3 and LI-cadherin) was apparent and these
      correlated with central obesity (correlation coefficient (CC)=0.604, p=0.001 and
      CC=0.462, p=0.002, respectively). In addition, expression of TFF-3 in distal
      oesophageal squamous mucosa correlated with proximal extension of gastric acidity
      within the region of the lower oesophageal sphincter (CC=-0.538, p=0.001).
      CONCLUSIONS: These findings are consistent with expansion of cardia in healthy
      volunteers occurring by squamo columnar metaplasia of distal oesophagus and
      aggravated by central obesity. This metaplastic origin of expanded cardia may be
      relevant to the substantial proportion of cardia adenocarcinomas unattributable
      to H. pylori or transsphincteric acid reflux.

PMID- 25753032
TI  - Quantitation of free light chains in the cerebrospinal fluid reliably predicts
      their intrathecal synthesis.
AB  - BACKGROUND: The results of free light chains quantitation in the cerebrospinal
      fluid were recently compared with the presence of cerebrospinal fluid-restricted
      oligoclonal IgG, but not oligoclonal free kappa light chains and oligoclonal free
      lambda light chains. We therefore aimed to compare the performance of the
      quantitative tests with the qualitative one for the same molecule. METHODS:
      Seventy-five paired cerebrospinal fluid and serum samples were analysed for
      oligoclonal IgG, oligoclonal free kappa light chains and oligoclonal free lambda
      light chains. Cerebrospinal fluid and serum free kappa and lambda light chains
      were quantified using FreeliteTM kits on SPA Plus analyzer. ROC curves were
      analysed for the prediction of intrathecal synthesis and compared for
      cerebrospinal fluid concentration, cerebrospinal fluid/serum quotient (QfLC) and
      index (QfLC/QAlbumin). The presence of cerebrospinal fluid-restricted oligoclonal
      free kappa light chains and oligoclonal free lambda light chains bands was used
      as reference. RESULTS: No statistically significant differences were observed
      among cerebrospinal fluid concentration, QfLC and index for the prediction of
      free light chain intrathecal synthesis. Each parameter was able to predict the
      occurrence of cerebrospinal fluid-restricted oligoclonal free light chain bands
      (AUCs 0.932-0.999). However, we noted elevated cerebrospinal fluid free light
      chain concentrations in the absence of cerebrospinal fluid-restricted oligoclonal
      free light chain bands in two patients with very high serum free light chain
      values. CONCLUSIONS: Quantitation of cerebrospinal fluid free light chains
      reliably predicts their intrathecal synthesis. Yet, cerebrospinal fluid/serum
      quotient may still be preferred to correct for high serum free light chain
      concentrations. An appropriate formula should be sought to correct for blood
      cerebrospinal fluid barrier status.

PMID- 25753033
TI  - Chemical cross-linking and mass spectrometry to determine the subunit interaction
      network in a recombinant human SAGA HAT subcomplex.
AB  - Understanding the way how proteins interact with each other to form transient or
      stable protein complexes is a key aspect in structural biology. In this study, we
      combined chemical cross-linking with mass spectrometry to determine the binding
      stoichiometry and map the protein-protein interaction network of a human SAGA HAT
      subcomplex. MALDI-MS equipped with high mass detection was used to follow the
      cross-linking reaction using bis[sulfosuccinimidyl] suberate (BS3) and confirm
      the heterotetrameric stoichiometry of the specific stabilized subcomplex. Cross
      linking with isotopically labeled BS3 d0-d4 followed by trypsin digestion allowed
      the identification of intra- and intercross-linked peptides using two dedicated
      search engines: pLink and xQuest. The identified interlinked peptides suggest a
      strong network of interaction between GCN5, ADA2B and ADA3 subunits; SGF29 is
      interacting with GCN5 and ADA3 but not with ADA2B. These restraint data were
      combined to molecular modeling and a low-resolution interacting model for the
      human SAGA HAT subcomplex could be proposed, illustrating the potential of an
      integrative strategy using cross-linking and mass spectrometry for addressing the
      structural architecture of multiprotein complexes. 

PMID- 25753034
TI  - LSR/angulin-1 is a tricellular tight junction protein involved in blood-brain
      barrier formation.
AB  - The blood-brain barrier (BBB) is a term used to describe the unique properties of
      central nervous system (CNS) blood vessels. One important BBB property is the
      formation of a paracellular barrier made by tight junctions (TJs) between CNS
      endothelial cells (ECs). Here, we show that Lipolysis-stimulated lipoprotein
      receptor (LSR), a component of paracellular junctions at points in which three
      cell membranes meet, is greatly enriched in CNS ECs compared with ECs in other
      nonneural tissues. We demonstrate that LSR is specifically expressed at
      tricellular junctions and that its expression correlates with the onset of BBB
      formation during embryogenesis. We further demonstrate that the BBB does not seal
      during embryogenesis in Lsr knockout mice with a leakage to small molecules.
      Finally, in mouse models in which BBB was disrupted, including an experimental
      autoimmune encephalomyelitis (EAE) model of multiple sclerosis and a middle
      cerebral artery occlusion (MCAO) model of stroke, LSR was down-regulated, linking
      loss of LSR and pathological BBB leakage. 

PMID- 25753035
TI  - Injury-stimulated Hedgehog signaling promotes regenerative proliferation of
      Drosophila intestinal stem cells.
AB  - Many adult tissues are maintained by resident stem cells that elevate their
      proliferation in response to injury. The regulatory mechanisms underlying
      regenerative proliferation are still poorly understood. Here we show that injury
      induces Hedgehog (Hh) signaling in enteroblasts (EBs) to promote intestinal stem
      cell (ISC) proliferation in Drosophila melanogaster adult midgut. Elevated Hh
      signaling by patched (ptc) mutations drove ISC proliferation noncell
      autonomously. Inhibition of Hh signaling in the ISC lineage compromised injury
      induced ISC proliferation but had little if any effect on homeostatic
      proliferation. Hh signaling acted in EBs to regulate the production of Upd2,
      which activated the JAK-STAT pathway to promote ISC proliferation. Furthermore,
      we show that Hh signaling is stimulated by DSS through the JNK pathway and that
      inhibition of Hh signaling in EBs prevented DSS-stimulated ISC proliferation.
      Hence, our study uncovers a JNK-Hh-JAK-STAT signaling axis in the regulation of
      regenerative stem cell proliferation. 

PMID- 25753036
TI  - Cdk1 phosphorylates SPAT-1/Bora to trigger PLK-1 activation and drive mitotic
      entry in C. elegans embryos.
AB  - The molecular mechanisms governing mitotic entry during animal development are
      incompletely understood. Here, we show that the mitotic kinase CDK-1
      phosphorylates Suppressor of Par-Two 1 (SPAT-1)/Bora to regulate its interaction
      with PLK-1 and to trigger mitotic entry in early Caenorhabditis elegans embryos.
      Embryos expressing a SPAT-1 version that is nonphosphorylatable by CDK-1 and that
      is defective in PLK-1 binding in vitro present delays in mitotic entry, mimicking
      embryos lacking SPAT-1 or PLK-1 functions. We further show that phospho-SPAT-1
      activates PLK-1 by triggering phosphorylation on its activator T loop in vitro by
      Aurora A. Likewise, we show that phosphorylation of human Bora by Cdk1 promotes
      phosphorylation of human Plk1 by Aurora A, suggesting that this mechanism is
      conserved in humans. Our results suggest that CDK-1 activates PLK-1 via SPAT-1
      phosphorylation to promote entry into mitosis. We propose the existence of a
      positive feedback loop that connects Cdk1 and Plk1 activation to ensure a robust
      control of mitotic entry and cell division timing. 

PMID- 25753037
TI  - LTP-triggered cholesterol redistribution activates Cdc42 and drives AMPA receptor
      synaptic delivery.
AB  - Neurotransmitter receptor trafficking during synaptic plasticity requires the
      concerted action of multiple signaling pathways and the protein transport
      machinery. However, little is known about the contribution of lipid metabolism
      during these processes. In this paper, we addressed the question of the role of
      cholesterol in synaptic changes during long-term potentiation (LTP). We found
      that N-methyl-d-aspartate-type glutamate receptor (NMDAR) activation during LTP
      induction leads to a rapid and sustained loss or redistribution of intracellular
      cholesterol in the neuron. A reduction in cholesterol, in turn, leads to the
      activation of Cdc42 and the mobilization of GluA1-containing alpha-amino-3
      hydroxy-5-methyl-4-isoxazolepropionic acid-type glutamate receptors (AMPARs) from
      Rab11-recycling endosomes into the synaptic membrane, leading to synaptic
      potentiation. This process is accompanied by an increase of NMDAR function and an
      enhancement of LTP. These results imply that cholesterol acts as a sensor of
      NMDAR activation and as a trigger of downstream signaling to engage small GTPase
      (guanosine triphosphatase) activation and AMPAR synaptic delivery during LTP. 

PMID- 25753038
TI  - GGCX and VKORC1 inhibit osteocalcin endocrine functions.
AB  - Osteocalcin (OCN) is an osteoblast-derived hormone favoring glucose homeostasis,
      energy expenditure, male fertility, brain development, and cognition. Before
      being secreted by osteoblasts in the bone extracellular matrix, OCN is gamma
      carboxylated by the gamma-carboxylase (GGCX) on three glutamic acid residues, a
      cellular process requiring reduction of vitamin K (VK) by a second enzyme, a
      reductase called VKORC1. Although circumstantial evidence suggests that gamma
      carboxylation may inhibit OCN endocrine functions, genetic evidence that it is
      the case is still lacking. Here we show using cell-specific gene inactivation
      models that gamma-carboxylation of OCN by GGCX inhibits its endocrine function.
      We further show that VKORC1 is required for OCN gamma-carboxylation in
      osteoblasts, whereas its paralogue, VKORC1L1, is dispensable for this function
      and cannot compensate for the absence of VKORC1 in osteoblasts. This study
      genetically and biochemically delineates the functions of the enzymes required
      for OCN modification and demonstrates that it is the uncarboxylated form of OCN
      that acts as a hormone. 

PMID- 25753039
TI  - ZO-1 controls endothelial adherens junctions, cell-cell tension, angiogenesis,
      and barrier formation.
AB  - Intercellular junctions are crucial for mechanotransduction, but whether tight
      junctions contribute to the regulation of cell-cell tension and adherens
      junctions is unknown. Here, we demonstrate that the tight junction protein ZO-1
      regulates tension acting on VE-cadherin-based adherens junctions, cell migration,
      and barrier formation of primary endothelial cells, as well as angiogenesis in
      vitro and in vivo. ZO-1 depletion led to tight junction disruption,
      redistribution of active myosin II from junctions to stress fibers, reduced
      tension on VE-cadherin and loss of junctional mechanotransducers such as vinculin
      and PAK2, and induced vinculin dissociation from the alpha-catenin-VE-cadherin
      complex. Claudin-5 depletion only mimicked ZO-1 effects on barrier formation,
      whereas the effects on mechanotransducers were rescued by inhibition of ROCK and
      phenocopied by JAM-A, JACOP, or p114RhoGEF down-regulation. ZO-1 was required for
      junctional recruitment of JACOP, which, in turn, recruited p114RhoGEF. ZO-1 is
      thus a central regulator of VE-cadherin-dependent endothelial junctions that
      orchestrates the spatial actomyosin organization, tuning cell-cell tension,
      migration, angiogenesis, and barrier formation. 

PMID- 25753040
TI  - Centrin2 regulates CP110 removal in primary cilium formation.
AB  - Primary cilia are antenna-like sensory microtubule structures that extend from
      basal bodies, plasma membrane-docked mother centrioles. Cellular quiescence
      potentiates ciliogenesis, but the regulation of basal body formation is not fully
      understood. We used reverse genetics to test the role of the small calcium
      binding protein, centrin2, in ciliogenesis. Primary cilia arise in most cell
      types but have not been described in lymphocytes. We show here that serum
      starvation of transformed, cultured B and T cells caused primary ciliogenesis.
      Efficient ciliogenesis in chicken DT40 B lymphocytes required centrin2. We
      disrupted CETN2 in human retinal pigmented epithelial cells, and despite having
      intact centrioles, they were unable to make cilia upon serum starvation, showing
      abnormal localization of distal appendage proteins and failing to remove the
      ciliation inhibitor CP110. Knockdown of CP110 rescued ciliation in CETN2
      deficient cells. Thus, centrin2 regulates primary ciliogenesis through
      controlling CP110 levels. 

PMID- 25753041
TI  - The mechanism of ion exchange and adsorption coexist on medium-low concentration
      ammonium-nitrogen removal by ion-exchange resin.
AB  - In this study, the removal of medium-low concentration ammonium-nitrogen
      ([Formula: see text]) from waters and wastewaters on D113 resin was investigated
      with respect to pH, initial [Formula: see text] concentration, temperature and
      contact time. The equilibrium of [Formula: see text] on D113 resin reached in 20
      30 min. The process of [Formula: see text] removal by D113 resin fitted Langmuir
      isotherm well. The pseudo second-order kinetic and intra-particle diffusion
      models were used to investigate the kinetic data of [Formula: see text] on D113
      resin. The desorption solution can be returned to production after pretreatment.
      The mechanism of removal of [Formula: see text] by D113 resin was coexistence of
      adsorption and cation exchange. When the dosage of D113 resin was 5 g L(-1), pH
      6, contact 30 min at room temperature, initial [Formula: see text] concentration
      being 116 mg L(-1) in rare earth metallurgical wastewater was reduced to 13 mg L(
      1) after adsorption treatment.

PMID- 25753042
TI  - A prolonged second stage should prompt increased vigilance for postpartum
      maternal complications.

PMID- 25753043
TI  - Pink melanocytic and non-melanocytic lesions: how reflectance confocal microscopy
      can help in differential diagnosis.

PMID- 25753044
TI  - Genetically engineered lymphocytes and adoptive cell therapy: cancer
      immunotherapy's smart bombs.

PMID- 25753045
TI  - Identification of miR-93 as a suitable miR for normalizing miRNA in plasma of
      tuberculosis patients.
AB  - Tuberculosis (TB) remains a major public health issue. New tests to aid diagnoses
      and monitor the response to therapy are urgently required. There is growing
      interest in the use of microRNA (miRNA) profiles as diagnostic, prognostic or
      predictive markers in a range of clinical and infectious diseases, including
      Mycobacterium tuberculosis infection, however, challenges exist to accurately
      normalise miRNA levels in cohorts. This study examined the appropriateness of 12
      miRs and RNU6B to normalise circulating plasma miRNA levels in individuals with
      active TB from 2 different geographical and ethnic regions. Twelve miRs (let-7,
      miR-16, miR-22, miR-26, miR-93, miR-103, miR-191, miR-192, miR-221, miR-423, miR
      425 and miR-451) and RNU6B were selected based on their reported production by
      lung cells, expression in blood and previous use as a reference miRNA. Expression
      levels were analysed in the plasma of newly diagnosed TB patients from Australia
      and China compared with individuals with latent TB infection and healthy
      volunteers. Analysis with both geNorm and NormFinder software identified miR-93
      as the most suitable reference miR in both cohorts, either when analysed
      separately or collectively. Interestingly, there were large variations in the
      expression levels of some miRs, in particular miR-192 and let-7, between the two
      cohorts, independent of disease status. These data identify miR-93 is a suitable
      reference miR for normalizing miRNA levels in TB patients, and highlight how
      environmental, and possibly ethnic, factors influence miRNA expression levels,
      demonstrating the necessity of assessing the suitability of reference miRs within
      the study population. 

PMID- 25753046
TI  - Emerging drug targets for Abeta and tau in Alzheimer's disease: a systematic
      review.
AB  - AIMS: Currently, treatment for Alzheimer's disease (AD) focuses on the
      cholinergic hypothesis and provides limited symptomatic effects. Research
      currently focuses on other factors that are thought to contribute to AD
      development such as tau proteins and Abeta deposits, and how modification of the
      associated pathology affects outcomes in patients. This systematic review
      summarizes and appraises the evidence for the emerging drugs affecting Abeta and
      tau pathology in AD. METHODS: A comprehensive, systematic online database search
      was conducted using the databases ScienceDirect and PubMed to include original
      research articles. A systematic review was conducted following a minimum set of
      standards, as outlined by The PRISMA Group . Specific inclusion and exclusion
      criteria were followed and studies fitting the criteria were selected. No human
      trials were included in this review. In vitro and in vivo AD models were used to
      assess efficacy to ensure studied agents were emerging targets without large
      bodies of evidence. RESULTS: The majority of studies showed statistically
      significant improvement (P < 0.05) of Abeta and/or tau pathology, or cognitive
      effects. Many studies conducted in AD animal models have shown a reduction in
      Abeta peptide burden and a reduction in tau phosphorylation post-intervention.
      This has the potential to reduce plaque formation and neuronal degeneration.
      CONCLUSIONS: There are many emerging targets showing promising results in the
      effort to modify the pathological effects associated with AD. Many of the trials
      also provided evidence of the clinical effects of such drugs reducing
      pathological outcomes, which was often demonstrated as an improvement of
      cognition.

PMID- 25753047
TI  - The plant cell wall.

PMID- 25753049
TI  - Modification of daunorubicin-GnRH-III bioconjugates with oligoethylene glycol
      derivatives to improve solubility and bioavailability for targeted cancer
      chemotherapy.
AB  - Daunorubicin-GnRH-III bioconjugates have recently been developed as drug delivery
      systems with potential applications in targeted cancer chemotherapy. In order to
      improve their biochemical properties, several strategies have been pursued: (1)
      incorporation of an enzymatic cleavable spacer between the anticancer drug and
      the peptide-based targeting moiety, (2) peptide modification by short chain fatty
      acids, or (3) attachment of two anticancer drugs to the same GnRH-III derivative.
      Although these modifications led to more potent bioconjugates, a decrease in
      their solubility was observed. Here we report on the design, synthesis and
      biochemical characterization of daunorubicin-GnRH-III bioconjugates with
      increased solubility, which could be achieved by incorporating oligoethylene
      glycol-based spacers in their structure. First, we have evaluated the effect of
      an oligoethylene glycol-based spacer on the solubility, enzymatic
      stability/degradation, cellular uptake, and in vitro cytostatic effect of a
      bioconjugate containing only one daunorubicin attached through a GFLG
      tetrapeptide spacer to the GnRH-III targeting moiety. Thereafter, more complex
      compounds containing two copies of daunorubicin, GFLG spacers as well as Lys(nBu)
      in position 4 of GnRH-III were synthesized and biochemically characterized. Our
      results indicated that all synthesized oligoethylene glycol-containing
      bioconjugates had higher solubility in cell culture medium than the unmodified
      analogs. They were degraded in the presence of rat liver lysosomal homogenate
      leading to the formation of small drug containing metabolites. In the case of
      bioconjugates containing two copies of daunorubicin, the incorporation of
      oligoethylene glycol-based spacers led to increased in vitro cytostatic effect on
      MCF-7 human breast cancer cells.

PMID- 25753051
TI  - Health promotion in Danish schools: local priorities, policies and practices.
AB  - This article discusses the findings from a study mapping out the priorities,
      policies and practices of local authorities concerning health promotion (HP) and
      health education (HE) in primary and lower secondary schools in Denmark. The aim
      of the study was to identify the gaps, tensions and possibilities associated with
      the demand to increase the quality and effectiveness of HP in schools. The recent
      national school reform, which emphasizes the importance of health and well-being
      while simultaneously increasing the focus on performance and accountability in
      terms of subject proficiency and narrowly defined academic attainment, provides
      the broader political context for the study. Data were generated through a
      structured online survey administered to all 98 Danish municipalities.
      Respondents were educational consultants or others representing the
      administrative units responsible for the municipality's schools. The findings
      were discussed within the conceptual framework of Health Promoting Schools. The
      study points to a potential tension between the health and education sectors,
      despite evidence of intersectoral collaboration. While there is a strong policy
      focus on health and well-being in schools, it is disconnected from the
      utilization of the HE curriculum by the municipal consultants. The study also
      points to a lack of professional development opportunities for teachers in the
      field of HP in schools. On the basis of these findings and theoretical
      perspectives used, we argue that HP in schools needs to (re)connect with the core
      task of the school, education, and to integrate both health and education goals
      in local priorities, policies and practices. 

PMID- 25753052
TI  - Allergic contact dermatitis caused by laurel leaf oil.

PMID- 25753048
TI  - Chronic wound repair and healing in older adults: current status and future
      research.
AB  - Older adults are more likely to have chronic wounds than younger people, and the
      effect of chronic wounds on quality of life is particularly profound in this
      population. Wound healing slows with age, but the basic biology underlying
      chronic wounds and the influence of age-associated changes on wound healing are
      poorly understood. Most studies have used in vitro approaches and various animal
      models, but observed changes translate poorly to human healing conditions. The
      effect of age and accompanying multimorbidity on the effectiveness of existing
      and emerging treatment approaches for chronic wounds is also unknown, and older
      adults tend to be excluded from randomized clinical trials. Poorly defined
      outcomes and variables; lack of standardization in data collection; and
      variations in the definition, measurement, and treatment of wounds also hamper
      clinical studies. The Association of Specialty Professors, in conjunction with
      the National Institute on Aging and the Wound Healing Society, held a workshop,
      summarized in this article, to explore the current state of knowledge and
      research challenges, engage investigators across disciplines, and identify
      research questions to guide future study of age-associated changes in chronic
      wound healing. 

PMID- 25753053
TI  - Long-term survival in octogenarians and older patients with ST-elevation
      myocardial infarction in the era of primary angioplasty: A prospective cohort
      study.
AB  - AIM: We aimed to study in-hospital mortality and long-term survival in elderly
      compared to younger patients with ST-segment elevation myocardial infarction
      (STEMI) in the era of primary angioplasty. METHODS AND RESULTS: This was a
      prospective cohort study. All consecutive STEMI-patients admitted to our hospital
      between September 2005-December 2011 were included in a local registry.
      Predefined variables were registered during hospital admission. Vital status was
      obtained from the Norwegian Cause of Death Registry with censoring date 31
      December 2011. Adjusted effects of age ?80 years on in-hospital- and long-term
      mortality were determined using propensity score analysis. Of 4525 registered
      STEMI patients, 600 (13%) were octogenarians or older. In-hospital mortality was
      17% in patients ?80 years and 4% in patients <80 years. In invasively treated
      patients (83% of patients ?80 years; 98% of patients <80 years), in-hospital
      mortality was 13% and 3.4%, respectively. Median follow-up time was 2.5 years.
      Three-year cumulative survival was 52% in patients ?80 years vs 89% in patients
      <80 years. In invasively treated patients ?80 years, three-year survival was 58%.
      The adjusted odds ratio of in-hospital mortality was 2.61 (1.94-3.52) and
      adjusted incidence rate ratio of long-term mortality was 4.07 (3.43-4.84) in very
      elderly compared to younger patients. CONCLUSION: Short-term prognosis was
      acceptable in very elderly STEMI patients, especially in the invasively treated
      subgroup. However, only 52% of STEMI patients ?80 years were alive after three
      years of follow-up. Very elderly patients had 2.6 times higher risk of in
      hospital mortality and 4.1 times the risk of not surviving during long-term
      follow-up compared to patients <80 years, after adjustment for confounding
      factors and selection bias.

PMID- 25753054
TI  - Role of politics in understanding complex, messy health systems: an essay by
      David J Hunter.

PMID- 25753055
TI  - A SEmi-Adiabatic matched-phase spin echo (SEAMS) PINS pulse-pair for B1 
      insensitive simultaneous multislice imaging.
AB  - PURPOSE: Simultaneous multislice (SMS) imaging is a powerful technique that can
      reduce image acquisition time for anatomical, functional, and diffusion weighted
      magnetic resonance imaging. At higher magnetic fields, such as 7 Tesla, increased
      radiofrequency (RF) field inhomogeneity, power deposition, and changes in
      relaxation parameters make SMS spin echo imaging challenging. We designed an
      adiabatic 180 degrees  Power Independent of Number of Slices (PINS) pulse and a
      matched-phase 90 degrees  PINS pulse to generate a SEmi-Adiabatic Matched-phase
      Spin echo (SEAMS) PINS sequence to address these issues. METHODS: We used the
      adiabatic Shinnar Le-Roux (SLR) algorithm to generate a 180 degrees  pulse. The
      SLR polynomials for the 180 degrees  pulse were then used to create a matched
      phase 90 degrees  pulse. The pulses were sub-sampled to produce a SEAMS PINS
      pulse-pair and the performance of this pulse-pair was validated in phantoms and
      in vivo. RESULTS: Simulations as well as phantom and in vivo results, demonstrate
      multislice capability and improved B1 -insensitivity of the SEAMS PINS pulse-pair
      when operating at RF amplitudes of up to 40% above adiabatic threshold.
      CONCLUSION: The SEAMS PINS approach presented here achieves multislice spin echo
      profiles with improved B1 -insensitivity when compared with a conventional spin
      echo.

PMID- 25753057
TI  - The constraints of distance and poverty on institutional deliveries in Pakistan:
      evidence from georeference-linked data.
AB  - While institutional deliveries in Pakistan have risen substantially over the last
      few years, the change has mainly occurred among the wealthy and those with access
      to services in urban areas. We assess the influence of economic and geographic
      access to health facilities on institutional deliveries by linking household
      survey data and georeferenced distance to facilities equipped to provide services
      for obstetric care in nine districts in Pakistan. Multilevel mixed-effect
      logistic regression analyses show that the net effect of an increase in distance
      to a facility by 1 kilometer is to decrease the odds of an institutional delivery
      by 3 percent. In contrast, household wealth and availability of at least basic
      emergency care within 10 kilometers substantially increase the odds of an
      institutional delivery. These effects are more pronounced in rural areas than in
      urban areas. Disadvantages faced by poor rural women can be minimized by
      upgrading existing facilities at district and subdistrict levels to provide
      comprehensive emergency care and by facilitating transportation of poor rural
      women directly to these facilities when they experience life-threatening
      complications of childbirth. 

PMID- 25753056
TI  - Peer Influences on Sexual Activity among Adolescents in Ghana.
AB  - Little is known about the influences of peers on the sexual activity of
      adolescents in sub-Saharan Africa. Better understanding of these issues could
      lead to more effective sexual and reproductive health interventions. Using two
      waves of survey data from 1,275 adolescents in two southeastern Ghanaian towns,
      we examine age, sex, and community differences in peer group characteristics. We
      also examine prospective associations between peer group characteristics and self
      reported sexual initiation and multiple partnerships during a 20-month follow-up
      period. Sex differences in peer-context variables were small. Affiliation with
      antisocial peers and perceived peer norms favoring sex increased the odds of
      transition to first sex. Having more friends increased the odds among younger
      respondents of acquiring multiple new sexual partners. Among males, perceived
      peer norms favoring sex increased the odds of acquiring multiple partners. We
      discuss the implications of these findings for adolescent sexual and reproductive
      health intervention strategies in sub-Saharan Africa, and conclude that peer
      based interventions may be best suited to the needs of at-risk adolescent boys. 

PMID- 25753058
TI  - Integrating population, health, and environment programs with contraceptive
      distribution in rural Ethiopia: a qualitative case study.
AB  - In rural Ethiopia, environmental degradation and a shortage of arable land impose
      a major toll on the population. Population, health, and environment (PHE)
      programs, such as that of the Ethio-Wetlands and Natural Resources Association
      (EWNRA), have evolved to address these issues. This article examines the
      community-based distribution (CBD) of family planning commodities in rural
      Ethiopia through EWNRA's large, multisectoral PHE program. Participants indicated
      that the integrated program encouraged acceptance of family planning and reduced
      geographic barriers to access. Through peer education and collaboration across
      government ministries, EWNRA leveraged integrated population-environment messages
      to garner support for its network of CBD providers. These integration strategies
      are a model for PHE programs worldwide, especially amid the global response to
      climate change. Because of the complex nature of PHE organizations, researchers
      often find it difficult to effectively document and evaluate their programs. With
      this in mind, we propose a framework to assess PHE integration. 

PMID- 25753059
TI  - Female sex workers' experiences with intended pregnancy and antenatal care
      services in southern Tanzania.
AB  - Understanding the pregnancy experiences of female sex workers (FSWs), especially
      in the context of high rates of HIV and sexually transmitted infections (STIs),
      is essential to tailoring services to meet their needs. This study explores FSWs'
      experiences with intended pregnancy and access to antenatal care and HIV testing
      in two regions of Tanzania. Thirty in-depth interviews and three focus group
      discussions were conducted. FSWs sought to become pregnant to gain respect as
      mothers, to avoid stigma, and/or to solidify relationships, sometimes posing
      risks to their own and their partners' health. Pregnant FSWs generally sought
      antenatal care (ANC) services but rarely disclosed their occupation, complicating
      provision of appropriate care. Accessing ANC services presented particular
      challenges, with health care workers sometimes denying all clinic services to
      women who were not accompanied by husbands. Several participants reported being
      denied care until delivery. The difficulties participants reported in accessing
      health care services as both sex workers and unmarried women have potential
      social and health consequences in light of the high levels of HIV and STIs among
      FSWs in sub-Saharan Africa. 

PMID- 25753060
TI  - Personal Beliefs and Professional Responsibilities: Ethiopian Midwives' Attitudes
      toward Providing Abortion Services after Legal Reform.
AB  - In 2005, Ethiopia liberalized its abortion law and subsequently authorized
      midwives to offer abortion services. Using a 2013 survey of 188 midwives and 12
      interviews with third-year midwifery students, this cross-sectional research
      examines midwives' attitudes toward abortion to understand their decisions about
      service provision. Most midwives were willing to provide abortion services. This
      willingness was positively and significantly related to clinical experience with
      abortion, but negatively and significantly related to religiosity, belief that
      providers have the right to refuse to provide services, and care of patients from
      periurban as opposed to rural areas. No significant relationship was found with
      perceptions of abortion stigma, years of work as a midwife, or knowledge of the
      law. Interview data suggest complex dynamics underlying midwives' willingness to
      offer services, including conflicts between professional norms and religious
      beliefs. Findings can inform Ethiopia's efforts to reduce maternal mortality
      through task-shifting to midwives and can aid other countries that are
      confronting provider shortages and high levels of maternal mortality and
      morbidity, particularly due to unsafe abortion. 

PMID- 25753061
TI  - Aligning goals, intents, and performance indicators in family planning service
      delivery.
AB  - A flurry of policy initiatives in the fields of both population and development
      and reproductive health, many addressing the provision of family planning
      services, are currently underway: FP2020, the ICPD Beyond 2014, and the post-2015
      development agenda, among others. This is an opportune time, therefore, to
      reflect upon and take into consideration what five decades of family planning
      programs can teach us about ensuring that policies and programs integrate their
      underlying intents, concrete goals, and performance indicators. The family
      planning field has encountered instances in its history when inconsistencies
      between goals, intents, and indicators arose and adversely affected the delivery
      of services. This commentary presents our observations concerning potential
      misalignments that may arise within the many promising initiatives underway. We
      examine the relationship between the intent, goal, and indicators of FP2020 as a
      case study highlighting the need for ensuring a tight alignment. We offer
      suggestions for ensuring that this and other initiatives use carefully calibrated
      indicators to guide the achievement of explicit program goals without undermining
      their underlying intent--namely, promoting well-being and reproductive rights.

PMID- 25753062
TI  - Guinea 2012 DHS.

PMID- 25753063
TI  - Tajikistan 2012 DHS.

PMID- 25753064
TI  - Evaluation of an intervention to individualise patient education at a nurse-led
      heart failure clinic: a mixed-method study.
AB  - AIMS AND OBJECTIVES: The main aim of this study was to evaluate whether
      addressing the written questions of heart failure patients could individualise
      the education and increase patient satisfaction. A further aim was to describe
      the learning needs of patients with newly diagnosed heart failure. BACKGROUND:
      Despite well-designed patient education, daily problems and self-care sometimes
      seem difficult to manage for the patient with heart failure. The literature
      suggested that nurses should include individualised educational interventions.
      DESIGN: The study had an evaluative and descriptive design. METHODS: A mixed
      method approach was used. A quasi-experimental method was used to compare
      patients in the control group (n = 41), who received regular education at the
      nurse-led heart failure clinic, with patients in the intervention group (n = 44),
      who received regular education but also education addressing questions they had
      written down at home before coming to the clinic. Two instruments were used to
      investigate, respectively, whether the intervention caused patients to experience
      a greater sense of involvement in their education and greater satisfaction. The
      patients' questions were subjected to manifest content analysis. RESULTS: There
      was no significant difference in satisfaction with the education between the
      control group and the intervention group. However, the intervention group did
      feel more strongly that the information they received was related to their
      personal situation. The patients' learning needs before education were
      categorised as: causes and meaning of illness, control and management of the
      disease, impact on daily living and future health. CONCLUSION: Asking heart
      failure patients to write down their learning needs before the education
      increases their chances of receiving education based on their individual needs.
      RELEVANCE TO CLINICAL PRACTICE: The method is simple and cost-effective and could
      be a way to improve the patient education and facilitate person-centred care.

PMID- 25753065
TI  - Complex karyotype, older age, and reduced first-line dose intensity determine
      poor survival in core binding factor acute myeloid leukemia patients with long
      term follow-up.
AB  - Approximately 40% of patients affected by core binding factor (CBF) acute myeloid
      leukemia (AML) ultimately die from the disease. Few prognostic markers have been
      identified. We reviewed 192 patients with CBF AML, treated with curative intent
      (age, 15-79 years) in 11 Italian institutions. Overall, 10-year overall survival
      (OS), disease-free survival (DFS), and event-free survival were 63.9%, 54.8%, and
      49.9%, respectively; patients with the t(8;21) and inv(16) chromosomal
      rearrangements exhibited significant differences at diagnosis. Despite similar
      high complete remission (CR) rate, patients with inv(16) experienced superior DFS
      and a high chance of achieving a second CR, often leading to prolonged OS also
      after relapse. We found that a complex karyotype (i.e., >=4 cytogenetic
      anomalies) affected survival, even if only in univariate analysis; the KIT D816
      mutation predicted worse prognosis, but only in patients with the t(8;21)
      rearrangement, whereas FLT3 mutations had no prognostic impact. We then observed
      increasingly better survival with more intense first-line therapy, in some high
      risk patients including autologous or allogeneic hematopoietic stem cell
      transplantation. In multivariate analysis, age, severe thrombocytopenia, elevated
      lactate dehydrogenase levels, and failure to achieve CR after induction
      independently predicted longer OS, whereas complex karyotype predicted shorter OS
      only in univariate analysis. The achievement of minimal residual disease
      negativity predicted better OS and DFS. Long-term survival was observed also in a
      minority of elderly patients who received intensive consolidation. All
      considered, we identified among CBF AML patients a subgroup with poorer prognosis
      who might benefit from more intense first-line treatment.

PMID- 25753066
TI  - Breast cyst fluid heparan sulphate is distinctively N-sulphated depending on
      apocrine or flattened type.
AB  - Breast cyst fluid (BCF) contained in gross cists is involved with its many
      biomolecules in different stages of breast cystic development. Type I apocrine
      and type II flattened cysts are classified based on biochemical, morphological
      and hormonal differences, and their different patterns of growth factors and
      active biocompounds may require different regulation. In a previous paper,
      hyaluronic acid in a very low content and chondroitin sulphate/dermatan sulphate
      were identified and characterized in BCF. In this new study, various apocrine and
      flattened BCFs were analyzed for HS concentration and disaccharide pattern.
      Apocrine HS was found specifically constituted of N-acetyl groups contrary to
      flattened HS richer in N-sulphate disaccharides with an overall N-acetylated/N
      sulphated ratio significantly increased in apocrine compared with flattened (13.5
      vs 3.7). Related to this different structural features, the charge density
      significantly decreased (~-30%) in apocrine versus flattened BCFs. Finally, no
      significant differences were observed for HS amount (~0.9-1.3 ug ml(-1) ) between
      the two BCF types even if a greater content was determined for flattened samples.
      The specifically N-sulphated sequences in flattened BCF HS can exert biologic
      capacity by regulating growth factors activity. On the other hand, we cannot
      exclude a peculiar regulation of the activity of biomolecules in apocrine BCF by
      HS richer in N-acetylated disaccharides. In fact, the different patterns of
      growth factors and active biocompounds in the two types of cysts may require
      different regulation by specific sequences in the HS backbone possessing specific
      structural characteristics and distinctive chemical groups.

PMID- 25753067
TI  - Unipotent Megakaryopoietic Pathway Bridging Hematopoietic Stem Cells and Mature
      Megakaryocytes.
AB  - Recent identification of platelet/megakaryocyte-biased hematopoietic
      stem/repopulating cells requires revision of the intermediate pathway for
      megakaryopoiesis. Here, we show a unipotent megakaryopoietic pathway bypassing
      the bipotent megakaryocyte/erythroid progenitors (biEMPs). Cells purified from
      mouse bone marrow by CD42b (GPIbalpha) marking were demonstrated to be unipotent
      megakaryocytic progenitors (MKPs) by culture and transplantation. A subpopulation
      of freshly isolated CD41(+) cells in the lineage Sca1(+) cKit(+) (LSK) fraction
      (subCD41(+) LSK) differentiated only into MKP and mature megakaryocytes in
      culture. Although CD41(+) LSK cells as a whole were capable of differentiating
      into all myeloid and lymphoid cells in vivo, they produced unipotent MKP, mature
      megakaryocytes, and platelets in vitro and in vivo much more efficiently than
      Flt3(+) CD41(-) LSK cells, especially at the early phase after transplantation.
      In single cell polymerase chain reaction and thrombopoietin (TPO) signaling
      analyses, the MKP and a fraction of CD41(+) LSK, but not the biEMP, showed the
      similarities in mRNA expression profile and visible TPO-mediated phosphorylation.
      On increased demand of platelet production after 5-FU treatment, a part of
      CD41(+) LSK population expressed CD42b on the surface, and 90% of them showed
      unipotent megakaryopoietic capacity in single cell culture and predominantly
      produced platelets in vivo at the early phase after transplantation. These
      results suggest that the CD41(+) CD42b(+) LSK are straightforward progenies of
      megakaryocytes/platelet-biased stem/repopulating cells, but not progenies of
      biEMP. Consequently, we show a unipotent/highly biased megakaryopoietic pathway
      interconnecting stem/repopulating cells and mature megakaryocytes, the one that
      may play physiologic roles especially in emergency megakaryopoiesis.

PMID- 25753068
TI  - From exposome to microbiome to infectome--'pathogens vs. sanogens'.

PMID- 25753069
TI  - Risk factors for community-acquired bacterial meningitis in adults.
AB  - Bacterial meningitis is a life-threatening infectious disease with high mortality
      and disability rates, despite availability of antibiotics and adjunctive therapy
      with dexamethasone. Several risk factors and predisposing conditions have been
      identified that increase susceptibility for bacterial meningitis. Such risk
      factors can consist of medical conditions resulting in immunodeficiency, host
      genetic factors or anatomical defects of the natural barriers of the central
      nervous system. These factors can increase the risk of meningitis in general or
      result in a specific risk of meningococcal or pneumococcal meningitis, the two
      most important causes of bacterial meningitis, which are characterised by
      distinct host-pathogen interactions. In this review we describe several risk
      factors for community-acquired bacterial meningitis in adults and discuss what
      preventive measurements can be taken in these populations.

PMID- 25753070
TI  - The gut microbiota in internal medicine: implications for health and disease.
AB  - The human gut microbiota may be viewed as an organ, executing numerous functions
      in metabolism, development of the immune system and host defence against
      pathogens. It may therefore be involved in the development of a range of diseases
      such as gastrointestinal infections, inflammatory bowel disease, allergy and
      diabetes mellitus. Reversely, certain therapies that are often used, such as
      antibiotics and chemotherapy, may negatively affect the composition and function
      of the gut microbiota and thereby the wellbeing of patients. As the microbiota
      research field is currently moving from association studies to intervention
      studies and even clinical trials, implementation of this new knowledge into
      clinical practice is coming near. Several therapeutic interventions that target
      the gut microbiota are being evaluated, ranging from supplementation of food
      components to transplantation of faecal microbiota. In this review we provide an
      overview of current literature on the gut microbiota in both a healthy state and
      a range of diseases that are relevant for internal medicine. In anticipation of
      gut microbiota-targeted therapies, it is important to realise the key function of
      the gut microbiota in physiological processes and the collateral damage that may
      be caused when disrupting this ecosystem within us. 

PMID- 25753071
TI  - The validity of national hospital discharge register data on dementia: a
      comparative analysis using clinical data from a university medical centre.
AB  - BACKGROUND: Most information on the incidence and prognosis of dementia comes
      from small studies with limited precision and generalisability. Nationwide
      registers can be an alternative source of information, but only when the
      diagnosis is validly recorded. We assessed the validity of the Dutch Hospital
      Discharge Register (HDR). METHODS: HDR data on dementia diagnoses (ICD-9 codes
      290.0; 290.1; 290.3; 290.4; 294.1; 331.0; 331.1; 331.82) in a university medical
      centre in the Netherlands were collected. Diagnoses were verified by using
      hospital medical records. Positive predictive values (PPVs) were calculated.
      Multivariate logistic regression models were used to evaluate determinants of
      inaccuracy in discharge diagnoses. RESULTS: A sample of the HDR data was used for
      this study (n = 340). PPV was 93.2% for overall dementia, indicating confirmation
      of 93.2% of HDR dementia diagnoses by the medical records. The accuracy of the
      diagnosis of overall dementia in patients aged >= 65 years was significantly
      higher compared with younger patients (PPV 95.5 % vs. 67.9%; p = 0.0001). There
      was no difference in the accuracy of the diagnosis between men and women and
      accuracy was not influenced by type of admission, comorbidity and polypharmacy.
      CONCLUSION: The results of this study show a high validity of the diagnosis of
      overall dementia in the HDR, making this register of great value for further
      nationwide research on dementia.

PMID- 25753072
TI  - Risk factors for gas-related complications of peroral endoscopic myotomy in
      achalasia.
AB  - BACKGROUND: Peroral endoscopic myotomy (POEM) is a novel endoscopic technique for
      the treatment of achalasia. However, there are POEM-associated complications, the
      most common of which being gas-related. The aim of the current study was to
      determine the occurrence of and risk factors for gas-related complications of
      POEM in patients with achalasia. METHODS: Retrospective analyses were performed
      on the clinical data of 216 achalasia patients receiving POEM at our hospital
      during the period from August 2011 to November 2013. Univariate and multivariate
      analyses were conducted to look for potential risk factors for gas-related
      complications. RESULTS: The rate of gas-related complications was 10.2% (22/216).
      Univariate analyses indicated that simple longitudinal mucosal incision, tunnel
      width <= 3 cm, sigmoid-type oesophagus, myotomy depth and operative time were
      risk factors for gas-related complications (p < 0.05). Multivariate analyses
      indicated that simple longitudinal mucosal incision, tunnel width <= 3 cm and
      sigmoid-type oesophagus were risk factors for the complications (p < 0.05).
      CONCLUSIONS: Simple longitudinal mucosal incision, tunnel width <= 3 cm and
      sigmoid-type oesophagus are independent risk factors for gas-related
      complications for achalasia during POEM, but not myotomy depth and operative
      time.

PMID- 25753073
TI  - A hypertensive emergency with acute visual impairment due to excessive liquorice
      consumption.
AB  - Hypokalaemic hypertension is the classical presentation of primary
      hyperaldosteronism but may also result from other mineralocorticoid activity,
      such as liquorice ingestion. Onset of hypertension as well as serum renin and
      aldosterone levels are central for the diagnosis. Liquorice ingestion has been
      reported to induce hypertension, hypokalaemia and metabolic alkalosis due to
      inhibition of the enzyme 11-beta-hydroxy steroiddehydrogenase 2. Here, we report
      the case of a hypertensive emergency with acute visual impairment due to
      hypertensive retinopathy in clear conjunction with a considerable consumption of
      liquorice.

PMID- 25753074
TI  - Solving a cold case of haemolysis: back to the basics.
AB  - Membrane disorders comprise an important group of inherited haemolytic anaemias.
      Diagnostic work-up starts with examination of the blood smear, followed by
      osmotic gradient ektacytometry. In special cases DNA analysis is performed to
      confirm the diagnosis. For this purpose a next-generation sequencing-based method
      has been developed. The combination of these techniques established the correct
      diagnosis in a case of haemolytic anaemia of unknown cause. 

PMID- 25753075
TI  - Take a deep breath....

PMID- 25753076
TI  - A man with erythema and blisters on his forearms.

PMID- 25753077
TI  - A purple finger two months after kidney transplantation.

PMID- 25753078
TI  - An unusual craving!

PMID- 25753079
TI  - Screening for Chlamydia trachomatis, Neisseria gonorrhoeae, and Mycoplasma
      genitalium should it be integrated into routine pregnancy care in French young
      pregnant women?
AB  - Chlamydia trachomatis, Neisseria gonorrhoeae, and Mycoplasma genitalium screening
      during pregnancy is not performed routinely in France. We conducted the first
      prospective study in 1004 women attending for routine antenatal care to determine
      the prevalence and risk factors for these bacterial infections. The overall
      prevalence of C. trachomatis, N. gonorrhoeae, and M. genitalium infections was
      2.5%, 0%, and 0.8%, respectively. In patients aged 18-24 years, the prevalence
      increased to 7.9% for C. trachomatis and to 2.4% for M. genitalium. C.
      trachomatis infection was associated with age <=24 years or being single or
      having more than 5 sexual partners in a lifetime. M. genitalium infection was
      more frequent in patients aged <=24 years or who had a history of abortion or
      their first sexual intercourse after 20 years of age. The high prevalence of C.
      trachomatis in pregnant women aged <=24 years, mostly asymptomatic, suggests that
      systematic screening could be beneficial.

PMID- 25753080
TI  - Determination of molecular species of calcium salts of MDP produced through
      decalcification of enamel and dentin by MDP-based one-step adhesive.
AB  - Enamel and dentin particles were added to an experimental 10-methacryloyloxydecyl
      dihydrogen phosphate (MDP)-based one-step adhesive to react for 30 s. After
      enamel and dentin reactants were analyzed using X-ray diffraction (XRD) and
      phosphorus-31 nuclear magnetic resonance ((31)P NMR) techniques, curve-fitting
      analysis was performed on the (31)P NMR spectra of enamel and dentin reactants.
      By varying the molar ratio of calcium chloride to MDP, a series of three types of
      MDP-Ca salts were synthesized. The molecular species of calcium salts of MDP (MDP
      Ca salts) produced by decalcification of enamel or dentin were determined based
      on the XRD and (31)P NMR analysis results of these three types of synthesized MDP
      Ca salts. Curve-fitting analysis showed that enamel and dentin developed several
      types of MDP-Ca salts and amorphous dicalcium phosphate dihydrate (DCPD) during
      decalcification. The molecular species of MDP-Ca salts produced by enamel and
      dentin were mono-calcium salts of MDP monomer and MDP dimer. In addition, dentin
      produced a di-calcium of MDP dimer. 

PMID- 25753081
TI  - An update on laparoscopic liver resection: The French Hepato-Bilio-Pancreatic
      Surgery Association statement.
AB  - Laparoscopic liver resection has been recognized as a safe and efficient approach
      since the Louisville Conference in 2008, but its use still remains confined to
      experienced teams in specialized centers, and may lack some standardization. The
      2013 Session of French Association for Hepatobiliary and Pancreatic Surgery
      (ACHBT) specifically focused on laparoscopic liver surgery and the particular
      aspects and issues arising since the 2008 conference. Our objective is to provide
      an update and summarize the current French position on laparoscopic liver
      surgery. An overview of the current practice of laparoscopic liver resections in
      France since 2008 is presented. The issues surrounding standardization for left
      lateral sectionectomy and right hepatectomy, hybrid and hand-assisted techniques
      are raised and discussed. Finally, future technologies and technical perspectives
      are outlined. 

PMID- 25753082
TI  - State governments' delays in fund transfer are affecting India's national health
      mission, report says.

PMID- 25753084
TI  - Do sperm possess a molecular passport? Mechanistic insights into sperm selection
      in the female reproductive tract.
AB  - Most male mammals produce far more spermatozoa on a daily basis than is strictly
      necessary for reproduction and females have evolved mechanisms that prevent all
      but a small minority from reaching the vicinity of their oocytes. One potential
      explanation for the stringent selection is that females have developed these
      mechanisms as a way of avoiding polyspermy as well as exercising post-copulatory
      choice over the characteristics of the fertilizing spermatozoon. Relatively
      little is known about how these processes would operate, but here we use evidence
      from biochemical, molecular and genetic studies of sperm transport in support of
      a hypothesis proposing that the female reproductive tract can read and interpret
      a spermatozoon's 'molecular passport' or genetic signature. Such a signature
      would permit only a highly selected sperm population to reach and fertilize the
      oocyte. Moreover, the selection criteria might not only be concerned with
      successful fertilizing ability, but could also be tailored to suit the genetic
      qualities of individual females. 

PMID- 25753083
TI  - The therapeuatic effect of Endostar on soft carotid plaque neovascularization in
      patients with non-small cell lung cancer.
AB  - The purpose of this study was to investigate the effect of the angiogenesis
      inhibitor Endostar on carotid plaque neovascularization in patients with non
      small cell lung cancer (NSCLC) using contrast-enhanced ultrasound (CEUS). Ninety
      one patients who had NSCLC with soft carotid plaques were selected for treatment
      either with the NP regimen (vinorelbine + cisplatin) (43 patients) or with the
      ENP regimen (Endostar + NP) (48 patients). Plaque thickness and
      neovascularization of the plaque were assessed before and at 1 month after
      treatment using CEUS. Enhanced intensity (EI) of CEUS was used for quantification
      of plaque neovascularization. There was no significant changes in any group in
      thickness of plaque between recruitment and 1 month after treatment (P > 0.05 for
      all). There was no significant change in the EI of plaque in the controls or NP
      groups at 1 month after treatment (P > 0.05), while EI in the ENP group was
      significantly reduced at 1 month after treatment (P < 0.01) and significantly
      lower than that in the controls or NP group at 1 month after treatment (P < 0.001
      both). This study indicates that carotid soft plaque neovascularization in
      patients with NSCLC can be reduced by anti-angiogenesis treatment. 

PMID- 25753085
TI  - Revision total knee arthroplasty: the end of the allograft era?

PMID- 25753086
TI  - Variable life-adjusted display (VLAD) for hip fracture patients: a prospective
      trial.
AB  - PURPOSE: With restructuring within the NHS, there is increased public and media
      interest in surgical outcomes. The Nottingham Hip Fracture Score (NHFS) is a well
      validated tool in predicting 30-day mortality in hip fractures. VLAD provides a
      visual plot in real time of the difference between the cumulative expected
      mortality and the actual death occurring. Survivors are incorporated as a
      positive value equal to 1 minus the probability of survival and deaths as a
      negative value equal to the probability of survival. Downward deflections
      indicate mortality and potentially suboptimal care. METHODS: We prospectively
      included every hip fracture admitted to UHW that underwent surgery from January
      August 2014. NHFS was then calculated and predicted survival identified. A VLAD
      plot was then produced comparing the predicted with the actual 30-day mortality.
      RESULTS: Two hundred and seventy-seven patients have completed the 30-day follow
      up, and initial results showed that the actual 30-day mortality (7.2 %) was much
      lower than that predicted by the NHFS (8.0 %). This was reflected by a positive
      trend on the VLAD plot. CONCLUSION: Variable life-adjusted display provides an
      easy-to-use graphical representation of risk-adjusted survival over time and can
      act as an "early warning" system to identify trends in mortality for hip
      fractures.

PMID- 25753087
TI  - A randomized controlled trial of postoperative analgesia following total knee
      replacement: transdermal Fentanyl patches versus patient controlled analgesia
      (PCA).
AB  - BACKGROUND: This randomized controlled trial compared a standard patient
      controlled analgesic (PCA) regime with a transdermal and oral Fentanyl regime for
      post-operative pain management in patients undergoing total knee replacement.
      METHODS: One hundred and ninety-six patients undergoing total knee replacement
      were recruited. Pre- and post-operatively Visual Analogue Score (VAS), Oxford
      Knee Score, Health Anxiety and Depression Score and Brief Pain Inventory Score
      were completed. According to the day 1, VAS score patients were randomly
      allocated to either a PCA regime or a Fentanyl transdermal/oral regime. Patient
      reported outcomes were measured until the patients were discharged. RESULTS: The
      results demonstrate that in terms of analgesic effect, day of discharge and side
      effect profile the two regimes are comparable. CONCLUSIONS: We conclude that a
      Fentanyl transdermal regime provides adequate analgesic effect comparable to a
      standard PCA regime in conjunction with a low side effect profile. Using a
      transdermal analgesic system provides efficient continuous delivery enabling a
      smooth transition from hospital to home within the first week. Transdermal
      Fentanyl provides an alternative analgesic regime that can provide an equivalent
      analgesic effect so as to enable a satisfactory outcome for the patient in terms
      of function and pain. LEVEL OF EVIDENCE: II.

PMID- 25753089
TI  - Resistance mounts to Ugandan plan to "export" hundreds of medical workers.

PMID- 25753088
TI  - Salvage of failed hip osteosynthesis for fractures with modular hip prosthesis.
AB  - BACKGROUND/PURPOSE: Treating options of failed internal fixation include revision
      fixation and salvage arthroplasty. The purpose of this study was to evaluate the
      results, complications and the final functional outcome associated with modular
      hip arthroplasty. METHODS: Modular arthroplasty was performed in 11 patients due
      to failed treatment of peritrochanteric fracture. Each patient examination
      included Trendelenburg test, Harris Hip Score, SF-36, and X-rays of the hip.
      Examinations were recorded and a paired t test was applied for further statistic
      analysis. RESULTS: Two years postoperatively, four patients referred no hip pain,
      seven patients claimed for slight or mild pain, and three patients presented with
      moderate pain. Statistical analysis revealed a statistically significant
      difference equally for Harris Hip Score and SF-36. CONCLUSION: The use of modular
      stems during salvage arthroplasty can decrease the risk of intraoperative and
      postoperative complications. The final outcome for the patient is satisfactory
      with functional improvement of the hip.

PMID- 25753091
TI  - Lack of correlation between the ventilatory response to CO2 and lung function
      impairment in myotonic dystrophy patients: evidence for a dysregulation at
      central level.
AB  - Myotonic dystrophy Type 1 (DM1) is the most common muscular dystrophy in adults.
      Respiratory failure is common but clinical findings support a dysregulation of
      the control of breathing at central level, furthermore contributing to alveolar
      hypoventilation independently of the severity of respiratory weakness. We
      therefore intended to study the relationship between the ventilatory response to
      CO2 and the impairment of lung function in DM1 patients. Sixty-nine DM1 patients
      were prospectively investigated (43.5 +/- 12.7 years). Systematic pulmonary lung
      function evaluation including spirometry, plethysmography, measurements of
      respiratory muscle strength, arterial blood gas analysis and ventilatory response
      to CO2 were performed. Thirty-one DM1 patients (45%) presented a ventilatory
      restriction, 38 (55%) were hypoxaemic and 15 (22%) were hypercapnic. Total lung
      capacity decline was correlated to hypoxaemia (p = 0.0008) and hypercapnia (p =
      0.0013), but not to a decrease in ventilatory response to CO2 (p = 0.194).
      Ventilatory response to CO2 was reduced to 0.85 +/- 0.67 L/min/mmHg and not
      correlated to respiratory muscle weakness. Ventilatory response to CO2 was
      neither different among restricted/non-restricted patients (p = 0.2395) nor among
      normoxaemic/hypoxaemic subjects (p = 0.6380). The reduced ventilatory response to
      CO2 in DM1 patients appeared independent of lung function impairment and
      respiratory muscle weakness, suggesting a central cause of CO2 insensitivity. 

PMID- 25753092
TI  - Effect of the oestrogen receptor antagonist fulvestrant on the cirrhotic rat
      lung.
AB  - It has been postulated that cirrhosis-related lung vasodilatation and the
      subsequent hepatopulmonary syndrome are partly explained by an increased
      estradiol level through an enhanced endothelial formation of nitric oxide (NO).
      In this study, we assessed whether the oestrogen receptor antagonist fulvestrant
      (F) improves cirrhosis-related lung abnormalities. Cirrhosis was induced in rats
      by chronic bile duct ligation (CBDL). Four groups were studied: CBDL, CBDL+F,
      sham, and sham+F. Histological, immunohistochemical, and Western blot analyses
      were performed on lung samples. In the lung, the endothelial NO synthase and the
      nitrotyrosine protein expressions were increased in CBDL as compared to sham
      rats. Both parameters were significantly reduced by fulvestrant in the CBDL rats.
      Surprisingly, the level of pVASP (an indirect marker of NO formation and action)
      was decreased in CBDL rats, and fulvestrant had no effect on this parameter. The
      level of the vascular endothelial growth factor, the diameter of small lung
      vessels, and the number of macrophages were increased in CBDL lungs in comparison
      with sham lungs, and these parameters were unaffected by fulvestrant treatment.
      In conclusion, fulvestrant may not be relevant to improve lung abnormalities in
      cirrhosis because NO may not be biologically active and because key events
      contributing to the lung abnormalities are not affected by fulvestrant. 

PMID- 25753093
TI  - The potential of translational bioinformatics approaches for pharmacology
      research.
AB  - The field of bioinformatics has allowed the interpretation of massive amounts of
      biological data, ushering in the era of 'omics' to biomedical research. Its
      potential impact on pharmacology research is enormous and it has shown some
      emerging successes. A full realization of this potential, however, requires
      standardized data annotation for large health record databases and molecular data
      resources. Improved standardization will further stimulate the development of
      system pharmacology models, using translational bioinformatics methods. This new
      translational bioinformatics paradigm is highly complementary to current
      pharmacological research fields, such as personalized medicine,
      pharmacoepidemiology and drug discovery. In this review, I illustrate the
      application of transformational bioinformatics to research in numerous
      pharmacology subdisciplines. 

PMID- 25753094
TI  - Gap Junctions Enhance the Antiproliferative Effect of MicroRNA-124-3p in
      Glioblastoma Cells.
AB  - MicroRNA (miRNA) holds promise as a novel therapeutic tool for cancer treatment.
      However, the transfection efficiency of current delivery systems represents a
      bottleneck for clinical applications. Here, we demonstrate that gap junctions
      mediate an augmentative effect on the antiproliferation mediated by miR-124-3p in
      U87 and C6 glioblastoma cells. The functional inhibition of gap junctions using
      either siRNA or pharmacological inhibition eliminated the miR-124-3p-mediated
      antiproliferation, whereas the enhancement of gap junctions with retinoic acid
      treatment augmented this miR-124-3p-mediated antiproliferation. A similar effect
      was observed in glioblastoma xenograft models. More importantly, patch clamp and
      co-culture assays demonstrated the transmission of miR-124-3p through gap
      junction channels into adjacent cells. In further exploring the impact of gap
      junction-mediated transport of miR-124-3p on miR-124-3p target pathways, we found
      that miR-124-3p inhibited glioblastoma cell growth in part by decreasing the
      protein expression of cyclin-dependent kinase 6, leading to cell cycle arrest at
      the G0 /G1 phase; moreover, pharmacological regulation of gap junctions affected
      this cell cycle arrest. In conclusion, our results indicate that the "bystander"
      effects of functional gap junctions composed of connexin 43 enhance the antitumor
      effect of miR-124-3p in glioblastoma cells by transferring miR-124-3p to adjacent
      cells, thereby enhancing G0 /G1 cell cycle arrest. These observations provide a
      new guiding strategy for the clinical application of miRNA therapy in tumor
      treatment.

PMID- 25753095
TI  - Prostate cancer: Orphan receptor GPR158 finds a home in prostate cancer growth
      and progression.

PMID- 25753100
TI  - Prostate cancer: 2-year ADT improves survival in patients receiving high-dose
      radiotherapy.

PMID- 25753101
TI  - Impact of axillary ultrasound (AUS) on axillary dissection in breast conserving
      surgery (BCS).
AB  - BACKGROUND AND OBJECTIVES: Preoperative axillary ultrasound (AUS) in clinically
      node-negative patients may increase axillary lymph node dissection (ALND) in
      ACoSOG Z0011-eligible patients. We hypothesize that AUS identifies operative
      axillary disease (>3 positive nodes) in women undergoing breast conserving
      surgery (BCS). METHODS: After IRB approval, a retrospective review of female
      breast cancer patients was performed; patients with clinical T1/T2 tumors
      undergoing BCS were included. Clinical, radiologic, and pathologic data were
      collected. RESULTS: Of 139 eligible subjects, 119/139 (86%) had nonpalpable
      axillary nodes. 47/119 patients (40%) had abnormal AUS and 15/47 (32%) had a
      positive FNA. Fourteen had ALND ;10/14 (71%) had >3 positive nodes. 6/32 (18%)
      with abnormal AUS but FNA negative were sentinel lymph node (SLN) positive. Of 72
      normal AUS, 15 (22%) were SLN positive; 9/15 (60%) had ALND; 1 (11%) had >3
      positive nodes. When evaluating for >3 positive nodes, AUS plus FNA had a
      sensitivity of 91%, specificity of 95%, NPV of 99%, and PPV of 71%. CONCLUSIONS:
      AUS/FNA has a high NPV for axillary metastasis and remarkable sensitivity for
      three or more positive axillary nodes, therefore AUS-identified metastasis should
      be treated as clinically node-positive disease, and is appropriate even in
      patients planning breast conserving surgery.

PMID- 25753102
TI  - Constitutive arsenite oxidase expression detected in arsenic-hypertolerant
      Pseudomonas xanthomarina S11.
AB  - Pseudomonas xanthomarina S11 is an arsenite-oxidizing bacterium isolated from an
      arsenic-contaminated former gold mine in Salsigne, France. This bacterium showed
      high resistance to arsenite and was able to oxidize arsenite to arsenate at
      concentrations up to 42.72 mM As[III]. The genome of this strain was sequenced
      and revealed the presence of three ars clusters. One of them is located on a
      plasmid and is organized as an "arsenic island" harbouring an aio operon and
      genes involved in phosphorous metabolism, in addition to the ars genes. Neither
      the aioXRS genes nor a specific sigma-54-dependent promoter located upstream of
      aioBA genes, both involved in regulation of arsenite oxidase expression in other
      arsenite-oxidizing bacteria, could be identified in the genome. This observation
      is in accordance with the fact that no difference was observed in expression of
      arsenite oxidase in P. xanthomarina S11, whether or not the strain was grown in
      the presence of As[III].

PMID- 25753103
TI  - A comparative study of Zingiber officinale Roscoe pulp and peel: phytochemical
      composition and evaluation of antitumour activity.
AB  - Colon cancer is one of the major causes of cancer mortality worldwide.
      Hydroalcoholic extract of ginger peel extract was more potent against colon
      cancer cells than ginger pulp hydroalcoholic extract using MTT assay, while
      ginger pulp hydroalcoholic extract showed higher anti-inflammatory and
      antioxidant activities. The two samples of ginger showed a different polyphenolic
      content and lipophilic composition. Peel extract possessed twice the polyphenolic
      content than pulp and the highest number of non-polar compounds. Among them,
      alpha-zingibirene was found to be the major constituent. The findings add to
      epidemiologic evidence for therapeutic effects of ginger peel in colorectal
      carcinoma. 

PMID- 25753105
TI  - An unusual case of an esophageal functional disorder.

PMID- 25753104
TI  - Etiology of diarrhea among children under the age five in China: Results from a
      five-year surveillance.
AB  - OBJECTIVES: Diarrhea is a leading cause of morbidity and mortality for children,
      although sparse data is available on the etiology of diarrhea in China. This
      study was conducted to determine main causes that underlie childhood diarrhea and
      related diseases. METHOD: Surveillance data for diarrhea was collected from 213
      participating hospitals between 2009 and 2013. These stool specimens, from
      children aged 0-59 months, were then analyzed for a panel of etiological agents
      consisting of 5 viruses, 8 bacteria and 3 protozoa. The proportion of children
      who tested positive for each pathogen was calculated and seasonal patterns for
      major organisms were determined. RESULTS: Pathogens were identified in 44.6% of
      the 32,189 samples from children with diarrhea. The most commonly detected
      pathogens were rotavirus (29.7% of cases), norovirus (11.8%), Diarrheagenic
      Escherichia coli (DEC; 5.0%), adenovirus (4.8%), non-typhoidal Salmonella (NTS;
      4.3%), and Shigella spp. (3.6%). A strong seasonal pattern was observed for these
      organisms, including rotavirus (winter), norovirus (autumn), and DEC, NTS, and
      Shigella (summer). CONCLUSION: A wide range of enteropathogens were detected in
      this five-year surveillance study; rotavirus and norovirus were most common among
      children under the age five. These findings should serve as robust evidence for
      public health entities when planning and developing national intervention
      programs in China.

PMID- 25753106
TI  - Predicting the risk for hospital-onset Clostridium difficile infection (HO-CDI)
      at the time of inpatient admission: HO-CDI risk score.
AB  - OBJECTIVE: To predict the likelihood of hospital-onset Clostridium difficile
      infection (HO-CDI) based on patient clinical presentations at admission DESIGN:
      Retrospective data analysis SETTING: Six US acute care hospitals PATIENTS: Adult
      inpatients METHODS: We used clinical data collected at the time of admission in
      electronic health record (EHR) systems to develop and validate a HO-CDI
      predictive model. The outcome measure was HO-CDI cases identified by a
      nonduplicate positive C. difficile toxin assay result with stool specimens
      collected >48 hours after inpatient admission. We fit a logistic regression model
      to predict the risk of HO-CDI. We validated the model using 1,000 bootstrap
      simulations. RESULTS: Among 78,080 adult admissions, 323 HO-CDI cases were
      identified (ie, a rate of 4.1 per 1,000 admissions). The logistic regression
      model yielded 14 independent predictors, including hospital community onset CDI
      pressure, patient age >=65, previous healthcare exposures, CDI in previous
      admission, admission to the intensive care unit, albumin <=3 g/dL, creatinine
      >2.0 mg/dL, bands >32%, platelets <=150 or >420 109/L, and white blood cell count
      >11,000 mm3. The model had a c-statistic of 0.78 (95% confidence interval [CI],
      0.76-0.81) with good calibration. Among 79% of patients with risk scores of 0-7,
      19 HO-CDIs occurred per 10,000 admissions; for patients with risk scores >20, 623
      HO-CDIs occurred per 10,000 admissions (P<.0001). CONCLUSION: Using clinical
      parameters available at the time of admission, this HO-CDI model demonstrated
      good predictive ability, and it may have utility as an early risk identification
      tool for HO-CDI preventive interventions and outcome comparisons.

PMID- 25753107
TI  - Unexpected fragmentations of triphosphaferrocene - formation of supramolecular
      assemblies containing the (1,2,4-P3C2Mes2)(-) ligand.
AB  - While reacting the sterically demanding triphosphaferrocene [Cp*Fe(eta(5)
      P3C2Mes2)] () with Cu(i) halides, the sandwich complex undergoes an unprecedented
      fragmentation into decamethylferrocene, FeX2 (X = Cl, Br, I) and [P3C2Mes2](-)
      units. Subsequently, these phospholyl ligands act as versatile, negatively
      charged building blocks for the formation of supramolecular aggregates
      representing the monomeric, dimeric and polymeric (1D and 2D) coordination
      compounds [(P3C2Mes2)2{Cu7(CH3CN)7(MU4-X)(MU3-X)2(MU-X)}{Cu2(MU2
      X)2X}{Cu(CH3CN)(MU2-X)}]2.6CH3CN (.6CH3CN: X = Cl, .6CH3CN: X = Br),
      [(P3C2Mes2)2{Cu(CH3CN)}6(MU-Br)2(MU3-Br)2{Cu(CH3CN)2Br}2].CH3CN (.CH3CN),
      [(P3C2Mes2)4{Cu5(CH3CN)5(MU2-Br)}{Cu(CH3CN)2CuBr2}2{Cu(CH3CN)2}]n(+)[CuBr2]n(
      ).2CH3CN (.2CH3CN), [(P3C2Mes2){Cu(CH3CN)(MU-I)}4{Cu(CH3CN)3}].0.5C7H8.2.5CH3CN
      (.0.5C7H8.2.5CH3CN), [(P3C2Mes2)Cu7(CH3CN)4(MU4-I)2(MU3-I)2(MU-I)2]x.2C7H8
      (.2C7H8), [(P3C2Mes2){Cu(CH3CN)3}2{Cu(MU-I)}6].0.5CH2Cl2.3CH3CN
      (.0.5CH2Cl2.3CH3CN) and [Cp*Fe(CH3CN)3]n(+)[(P3C2Mes2)2{Cu(CH3CN)2}{Cu(MU-I)}6]n(
      ).0.6CH2Cl2 (.0.6CH2Cl2) with rather non-typical structural motifs within the
      large varieties of copper halide chemistry. Besides the X-ray structural analyses
      the obtained assemblies were also characterized in solution in which they undergo
      fragmentation and re-aggregation processes. 

PMID- 25753108
TI  - Rates of caesarean vary widely across Europe.

PMID- 25753109
TI  - Beating beats mixing in heterodyne detection schemes.
AB  - Heterodyne detection schemes are widely used to detect and analyse high-frequency
      signals, which are unmeasurable with conventional techniques. It is the general
      conception that the heterodyne signal is generated only by mixing and that
      beating can be fully neglected, as it is a linear effect that, therefore, cannot
      produce a heterodyne signal. Deriving a general analytical theory, we show, in
      contrast, that both beating and mixing are crucial to explain the heterodyne
      signal generation. Beating even dominates the heterodyne signal, if the
      nonlinearity of the mixing element (mixer) is of higher order than quadratic. The
      specific characteristic of the mixer determines its sensitivity for beating. We
      confirm our results with both a full numerical simulation and an experiment using
      heterodyne force microscopy, which represents a model system with a highly non
      quadratic mixer. As quadratic mixers are the exception, many results of
      previously reported heterodyne measurements may need to be reconsidered. 

PMID- 25753110
TI  - Detection of subnanotesla oscillatory magnetic fields using MRI.
AB  - PURPOSE: Direct mapping of neuronal currents using MRI would have fundamental
      impacts on brain functional imaging. Previous reports indicated that the stimulus
      induced rotary saturation (SIRS) mechanism had the best potential of direct
      detection of neural oscillations; however, it lacked the high-sensitivity level
      needed. In this study, a novel strategy is proposed in an effort to improve the
      detection sensitivity. METHODS: In our modified SIRS sequence, an external
      oscillatory magnetic field is used as the excitation pulse in place of the
      standard 90-degree excitation pulse. This approach could potentially lead to tens
      or even hundreds times of enhancement in the detection sensitivity for low field
      signals. It also helps to lower the physiological noise, allows for shorter pulse
      repetition time, and is less affected by the blood oxygen level. RESULTS: We
      demonstrate that a 100-Hz oscillatory magnetic field with magnitude as low as
      0.25 nanotesla generated in a current loop can be robustly detected using a 3
      Tesla MRI scanner. CONCLUSION: The modified SIRS sequence offers higher detection
      sensitivity as well as several additional advantages. These promising results
      suggest that the direct detection of neural oscillation might be within the grasp
      of the current MRI technology.

PMID- 25753111
TI  - The impact of robotics on the mode of benign hysterectomy and clinical outcomes.
AB  - BACKGROUND: The impact of robotics on benign hysterectomy surgical approach,
      clinical outcomes, and learning curve is still unclear. METHODS: Review of
      abdominal, vaginal, laparoscopic, or robotic cases in 156 US hospitals in the
      Premier Research Database. RESULTS: Of 289 875 hysterectomies, abdominal cases
      decreased from 2005-2010 (60-33%) and minimally invasive approaches increased (40
      67%). Conversion rates were: 0.04% for vaginal, 2.5% for robotic, and 7.2% for
      laparoscopy (P < 0.001). Robotic surgery time was longest (3.4 h vs. 2.2 vaginal,
      2.5 abdominal, 2.7 laparoscopy, P < 0.001). Robotic complication rate was lowest
      (14.8% vs. 16.2% vaginal, 18.6% laparoscopy, 28.9% abdominal, P < 0.001).
      Hospital stay was longer following abdominal surgery (3.5 days vs. 1.8 robotic,
      1.9 vaginal, 1.8 laparoscopy, P < 0.001). Robotic surgery times and conversion
      and complication rates improved with experience (2.8 h, 2%, and 13.9%,
      respectively), even with increasing complexity. CONCLUSIONS: Robotics was
      successfully incorporated without jeopardizing patient outcomes and increased the
      overall use of minimally invasive approaches.

PMID- 25753112
TI  - Intramitochondrial accumulation of cationic Atto520-biotin proceeds via voltage
      dependent slow permeation through lipid membrane.
AB  - Conjugation to penetrating cations is a general approach for intramitochondrial
      delivery of physiologically active compounds, supported by a high membrane
      potential of mitochondria having negative sign on the matrix side. By using
      fluorescence correlation spectroscopy, we found here that Atto520-biotin, a
      conjugate of a fluorescent cationic rhodamine-based dye with the membrane
      impermeable vitamin biotin, accumulated in energized mitochondria in contrast to
      biotin-rhodamine 110. The energy-dependent uptake of Atto520-biotin by
      mitochondria, being slower than that of the conventional mitochondrial dye
      tetramethyl-rhodamine ethyl ester, was enhanced by the hydrophobic anion
      tetraphenylborate (TPB). Atto520-biotin also exhibited accumulation in liposomes
      driven by membrane potential resulting from potassium ion gradient in the
      presence valinomycin. The induction of electrical current across planar bilayer
      lipid membrane by Atto520-biotin proved the ability of the compound to permeate
      through lipid membrane in a cationic form. Atto520-biotin stained mitochondria in
      a culture of L929 cells, and the staining was enhanced in the presence of TPB.
      Therefore, the fluorescent Atto520 moiety can serve as a vehicle for
      intramitochondrial delivery of hydrophilic drugs. Of importance for biotin
      streptavidin technology, binding of Atto520-biotin to streptavidin was found to
      cause quenching of its fluorescence similar to the case of fluorescein-4-biotin. 

PMID- 25753113
TI  - Fluorescence microscopy colocalization of lipid-nucleic acid nanoparticles with
      wildtype and mutant Rab5-GFP: A platform for investigating early endosomal
      events.
AB  - Endosomal entrapment is known to be a major bottleneck to successful cytoplasmic
      delivery of nucleic acids (NAs) using cationic liposome-NA nanoparticles (NPs).
      Quantitative measurements of distributions of NPs within early endosomes (EEs)
      have proven difficult due to the sub-resolution size and short lifetime of
      wildtype EEs. In this study we used Rab5-GFP, a member of the large family of
      GTPases which cycles between the plasma membrane and early endosomes, to
      fluorescently label early endosomes. Using fluorescence microscopy and
      quantitative image analysis of cells expressing Rab5-GFP, we found that at early
      time points (t<1h), only a fraction (~35%) of RGD-tagged NPs (which target cell
      surface integrins) colocalize with wildtype EEs, independent of the NP's membrane
      charge density. In comparison, a GTP-hydrolysis deficient mutant, Rab5-Q79L,
      which extends the size and lifetime of EEs yielding giant early endosomes (GEEs),
      enabled us to resolve and localize individual NPs found within the GEE lumen.
      Remarkably, nearly all intracellular NPs are found to be trapped within GEEs
      implying little or no escape at early time points. The observed small degree of
      colocalization of NPs and wildtype Rab5 is consistent with recycling of Rab5-GDP
      to the plasma membrane and not indicative of NP escape from EEs. Taken together,
      our results show that endosomal escape of PEGylated nanoparticles occurs
      downstream of EEs i.e., from late endosomes/lysosomes. Our studies also suggest
      that Rab5-Q79L could be used in a robust imaging assay which allows for direct
      visualization of NP interactions with the luminal membrane of early endosomes. 

PMID- 25753115
TI  - Fitness and cardiovascular health, not just a European issue.

PMID- 25753114
TI  - Solution structure of the transmembrane 2 domain of the human melanocortin-4
      receptor in sodium dodecyl sulfate (SDS) micelles and the functional implication
      of the D90N mutant.
AB  - The melanocortin receptors (MCRs) are members of the G protein-coupled receptor
      (GPCR) 1 superfamily with seven transmembrane (TM) domains. Among them, the
      melanocortin-4 receptor (MC4R) subtype has been highlighted recently by genetic
      studies in obese humans. In particular, in a patient with severe early-onset
      obesity, a novel heterozygous mutation in the MC4R gene was found in an exchange
      of Asp to Asn in the 90th amino acid residue located in the TM 2 domain
      (MC4RD90N). Mutations in the MC4R gene are the most frequent monogenic causes of
      severe obesity and are described as heterozygous with loss of function. We
      determine solution structures of the TM 2 domain of MC4R (MC4RTM2) and compared
      secondary structure of Asp90 mutant (MC4RTM2-D90N) in a micelle environment by
      nuclear magnetic resonance (NMR) spectroscopy. NMR structure shows that MC4RTM2
      forms a long alpha-helix with a kink at Gly98. Interestingly, the structure of
      MC4RTM2-D90N is similar to that of MC4RTM2 based on data from CD and NMR
      spectrum. However, the thermal stability and homogeneity of MC4RD90N is quite
      different from those of MC4R. The structure from molecular modeling suggests that
      Asp90(2.50) plays a key role in allosteric sodium ion binding. Our data suggest
      that the sodium ion interaction of Asp90(2.50) in the allosteric pocket of MC4R
      is essential to its function, explaining the loss of function of the MC4RD90N
      mutant.

PMID- 25753117
TI  - Not all thromboembolism comes from the left atrial appendage in atrial
      fibrillation.

PMID- 25753116
TI  - Prognosis importance of low flow in aortic stenosis with preserved LVEF.
AB  - AIMS: Previous studies using echocardiography suggested that a low flow (LF)
      defined as an indexed stroke volume (SVi) <35 mL/m(2) may be an important
      determinant of outcome in patients with severe aortic stenosis (AS). We sought to
      assess the prognostic importance of stroke volume derived from invasive data. The
      aim of this study was to determine the impact of LF, purposely derived from
      cardiac catheterisation data, on outcome of patients with severe AS and preserved
      LVEF. METHODS: Between 2000 and 2010, 768 patients with preserved LVEF (>50%) and
      severe AS (valve area <=1 cm(2)) without other valvular heart disease underwent
      cardiac catheterisation. The long-term overall mortality was assessed as the
      primary end-point. RESULTS: Mean age was 74+/-8 years, 58% were men, 46% had
      coronary artery disease and mean LVEF was 72+/-10%. Low SVi was found in 27%
      (n=210) of patients with AS. As compared with patients with normal SVi, those
      with low SVi were significantly older (p<0.0001) with higher rate of atrial
      fibrillation (p<0.0001). Additionally, they had lower LVEF (p=0.046), aortic
      valve area (p<0.0001), mean pressure gradient (p<0.0001), systemic arterial
      compliance (p<0.0001) and higher systemic vascular resistances (p<0.0001). Eight
      year survival was significantly reduced in patients with low SVi as compared with
      those with normal SVi (51+/-5% vs 67+/-3%; p<0.0001). After adjustment for all
      other risk factors, reduced SVi was independently associated with long-term
      mortality (HR=1.45, 95% CI 1.1 to 2.1; p=0.048). CONCLUSIONS: In patients with
      severe AS and preserved LVEF, LF, as assessed using cardiac catheterisation is
      frequent, and is an independent predictor of mortality. Consequently, the
      measurement of SVi should be systematically included in the assessment of these
      patients.

PMID- 25753118
TI  - Close the appendage, open the future.

PMID- 25753121
TI  - Proteomic profile of the skin mucus of farmed gilthead seabream (Sparus aurata).
AB  - Fish skin mucus is the first line of defense against infections and it
      discriminates between pathogenic and commensal bacterial strains. Mucus
      composition varies amongst fish species and is influenced by endogenous and
      exogenous factors. This study describes the first proteome map of the epidermal
      mucus of farmed gilthead seabream (Sparus aurata). We used an integrative
      proteomic approach by combining a label-free procedure (LC-MS/MS) with the
      classical 2-DE-PMF-MS/MS methodology. The identified mucosal proteins were
      clustered in four groups according to their biological functions. Structural
      proteins (actins, keratins, tubulins, tropomyosin, cofilin-2 and filamin-A) and
      metabolic proteins (ribosomal proteins, proteasomal subunits, NACA, VCP,
      histones, NDPK, transferrin, glycolytic enzymes, ATP synthase components, beta
      globin, Apo-A1 and FABP7) were the best represented functional categories. We
      also found proteins involved in stress response (WAP65, HSPC70, Cu,Zn-SOD, and
      PRDX1 and PRDX2) and signal transduction (PP2A 65kDa regulatory subunit, 14-3-3
      protein beta/alpha, tyrosine 3-monooxygenase/tryptophan 5-monooxygenase
      activation protein, RhoGDI and PEBP1). Most of the identified proteins address
      different aspects of the innate immune response. Additionally, we analyzed
      bacterial peptides identified in the skin mucus of healthy S. aurata. These
      results revealed that genera belonging to the Lactobacillales order constitute
      the most abundant microorganism populations in this habitat. BIOLOGICAL
      SIGNIFICANCE: This work shows that proteomic methods can be used to characterize
      fish skin mucus. Using a coupled approach of LC-MS/MS and a 2-DE-PMF-MS/MS, we
      have obtained the first comprehensive view of the skin mucosal proteome of S.
      aurata, a fish species that is economically relevant for Mediterranean
      aquaculture. We identified a panel of proteins involved in a variety of
      biological functions, particularly in the innate immune response. Furthermore, to
      our knowledge, this is the first time a proteomic approach has been used to
      examine the microbiota in the skin mucus of a fish species. Overall, these
      results support further immunological researches in S. aurata and are relevant
      for the culture of this important fish species.

PMID- 25753120
TI  - Exposure to diethylstilbestrol during pregnancy modulates microRNA expression
      profile in mothers and fetuses reflecting oncogenic and immunological changes.
AB  - Prenatal exposure to diethylstilbestrol (DES) is known to cause an increased
      susceptibility to a wide array of clinical disorders in humans. Previous studies
      from our laboratory demonstrated that prenatal exposure to DES induces thymic
      atrophy and apoptosis in the thymus. In the current study, we investigated if
      such effects on the thymus result from alterations in the expression of microRNA
      (miR). To that end, pregnant C57BL/6 mice who were exposed to DES and miR
      profiles in thymocytes of both the mother and fetuses on postnatal day 3
      (gestation day 17) were studied. Of the 609 mouse miRs examined, we noted 59
      altered miRs that were common for both mothers and fetuses, whereas 107 altered
      miRs were specific to mothers only and 101 altered miRs were specific to fetuses
      only. Upon further analyses in the fetuses, we observed that DES-mediated changes
      in miR expression may regulate genes involved in important functions, such as
      apoptosis, autophagy, toxicity, and cancer. Of the miRs that showed decreased
      expression following DES treatment, miR-18b and miR-23a were found to possess
      complementary sequences and binding affinity for 3' untranslated regions of the
      Fas ligand (FasL) and Fas, respectively. Transfection studies confirmed that DES
      mediated downregulation of miR-18b and miR-23a led to increased FasL and Fas
      expression. These data demonstrated that prenatal DES exposure can cause
      alterations in miRs, leading to changes in the gene expression, specifically, miR
      mediated increased expression in FasL and Fas causing apoptosis and thymic
      atrophy. 

PMID- 25753122
TI  - Serum proteomics in multiple sclerosis disease progression.
AB  - Multiple sclerosis (MS) is associated with chronic degeneration of the central
      nervous system and may cause permanent neurological problems and considerable
      disability. While its causes remain unclear, its extensive phenotypic variability
      makes its prognosis and treatment difficult. The identification of serum
      proteomic biomarkers of MS progression could further our understanding of the
      molecular mechanisms related to MS disease processes. In the current study, we
      used isobaric tagging for relative and absolute protein quantification (iTRAQ)
      methodology and advanced multivariate statistical analysis to quantify and
      identify potential serum biomarker proteins of MS progression. We identified a
      panel of 11 proteins and combined them into a classifier that best classified
      samples into the two disease groups. The estimated area under the receiver
      operating curve of this classifier was 0.88 (p-value=0.017), with 86% sensitivity
      and specificity. The identified proteins encompassed processes related to
      inflammation, opsonization, and complement activation. Results from this study
      are in particular valuable to design a targeted Multiple Reaction Monitoring mass
      spectrometry based (MRM-MS) assay to conduct an external validation in an
      independent and larger cohort of patients. Validated biomarkers may result in the
      development of a minimally-invasive tool to monitor MS progression and complement
      current clinical practices. BIOLOGICAL SIGNIFICANCE: A hallmark of multiple
      sclerosis is the unpredictable disease course (progression). There are currently
      no clinically useful biomarkers of MS disease progression; most work has focused
      on the analysis of CSF, which requires an invasive procedure. Here, we explore
      the potential of proteomics to identify panels of serum biomarkers of disease
      progression in MS. By comparing the protein signatures of two challenging to
      obtain, but well-defined, MS phenotypic groups at the extremes of progression
      (benign and aggressive cases of MS), we identified proteins that encompass
      processes related to inflammation, opsonization, and complement activation.
      Findings require validation, but are an important step on the pathway to
      clinically useful biomarker discovery. This article is part of a Special Issue
      entitled: Protein dynamics in health and disease. Guest Editors: Pierre Thibault
      and Anne-Claude Gingras.

PMID- 25753124
TI  - Use of MALDI-TOF mass spectrometry fingerprinting to characterize Enterococcus
      spp. and Escherichia coli isolates.
AB  - Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry
      (MALDI-TOF MS) is a faster and more accurate method to identify intact bacteria
      than conventional microbiology and/or molecular biology methods. The MALDI-TOF MS
      method is potentially applicable in diagnostic laboratories to characterize
      commensal bacterial species, some of which are major pathogens, from human or
      animal gastrointestinal tracts. The aim of this study was to analyze at the
      cluster and statistical level the capacity of MALDI-TOF MS to distinguish between
      previously characterized enterococci and Escherichia coli isolated from wild
      birds of the Azores archipelago. Soluble proteins were extracted from intact cell
      cultures of 60 isolates of Enterococcus spp. and 60 isolates of E. coli by an
      expedient method. MALDI-TOF MS was used to obtain 1200 mass spectra that were
      statistically analyzed and compared. A total of 215 distinct mass-to-charge (m/z)
      peaks were obtained, including a peak at m/z 4428+/-3, which is exclusively found
      in spectra from Enterococcus isolates, and peaks at m/z 5379+/-3 and m/z 6253+/
      3, which are only detected in spectra from E. coli isolates. By processing mass
      spectra and analyzing them statistically with MassUp software, including
      principal component analysis (PCA) and clustering, it was possible to correctly
      distinguish between isolates of Enterococcus and Escherichia genera. The results
      of the proteomic analysis confirm that these tools could be used to characterize
      whole bacterial cells. In the future, with an optimized protocol for obtaining
      plasmid-associated proteins and the further development of bioinformatics
      methods, it is likely that mass peak characteristic of antimicrobial resistance
      will be detected, increasing the potential usefulness of MALDI-TOF in routine
      clinical assays. BIOLOGICAL SIGNIFICANCE: This study highlights the importance of
      MALDI-TOF MS in the rapid and reliable identification of bacteria by whole-cell
      analysis. The mass spectrometry approach performed in this study further
      contributes for the microbial biomarker discovery culminating in a preferable
      bacteria identification and antimicrobial resistance tool for the future of
      clinical microbiology. This article is part of a Special Issue entitled: HUPO
      2014.

PMID- 25753123
TI  - Label-free quantitative proteomics to investigate strawberry fruit proteome
      changes under controlled atmosphere and low temperature storage.
AB  - To elucidate the mechanisms contributing to fruit responses to senescence and
      stressful environmental stimuli under low temperature (LT) and controlled
      atmosphere (CA) storage, a label-free quantitative proteomic investigation was
      conducted in strawberry (Fragaria ananassa, Duch. cv. 'Akihime'). Postharvest
      physiological quality traits including firmness, total soluble solids, total
      acidity, ascorbic acid and volatile production were characterized following
      storage under different conditions. The observed post-storage protein expression
      profiles may be associated with delayed senescence features in strawberry. A
      total of 454 proteins were identified in differentially treated strawberry
      fruits. Quantitative analysis, using normalized spectral counts, revealed 73
      proteins common to all treatments, which formed three clusters in a hierarchical
      clustering analysis. The proteins spanned a range of functions in various
      metabolic pathways and networks involved in carbohydrate and energy metabolism,
      volatile biosynthesis, phenylpropanoid activity, stress response and protein
      synthesis, degradation and folding. After CA and LT storage, 16 (13) and 11 (17)
      proteins, respectively, were significantly increased (decreased) in abundance,
      while expression profile of 12 proteins was significantly changed by both CA and
      LT. To summarize, the differential variability of abundance in strawberry
      proteome, working in a cooperative manner, provided an overview of the biological
      processes that occurred during CA and LT storage. BIOLOGICAL SIGNIFICANCE:
      Controlled atmosphere storage at an optimal temperature is regarded to be an
      effective postharvest technology to delay fruit senescence and maintain fruit
      quality during shelf life. Nonetheless, little information on fruit proteomic
      changes under controlled atmosphere and/or low temperature storage is available.
      The significance of this paper is that it is the first study employing a label
      free approach in the investigation of strawberry fruit response to controlled
      atmosphere and cold storage. Changes in postharvest physiological quality traits
      including volatile production, firmness, ascorbic acid, soluble solids and total
      acidity were also characterized. Significant biological changes associated with
      senescence were revealed and differentially abundant proteins under various
      storage conditions were identified. Proteomic profiles were linked to
      physiological aspects of strawberry fruit senescence in order to provide new
      insights into possible regulation mechanisms. Findings from this study not only
      provide proteomic information on fruit regulation, but also pave the way for
      further quantitative studies at the transcriptomic and metabolomic levels.

PMID- 25753125
TI  - Unraveling the proteomic profile of mice testis during the initiation of meiosis.
AB  - In mice, once primordial germ cells (PGCs) are generated, they continue to
      proliferate and migrate to eventually reach the future gonads. They initiate
      sexual differentiation after their colonization of the gonads. During this
      process, retinoic acid (RA) induces meiosis in the female germ cells, which
      proceeds to the diplotene stage of meiotic prophase I, whereas the male germ
      cells initiate growth arrest. After birth, meiosis is initiated in mice
      spermatogonia by their conversion to preleptotene spermatocytes. There are
      evidences showing the roles of RA in the regulation of spermatogonial
      differentiation and meiosis initiation. However, it is still not well known on
      what responds to RA and how RA signaling engages meiosis. Thus, we constructed a
      proteomic profile of proteins associated with meiosis onset during testis
      development in mouse and identified 104 differentially expressed proteins (>=1.5
      folds). Bioinformatic analysis showed proteins functioning in specific cell
      processes. The expression patterns of five selected proteins were verified via
      Western blot, of which we found that Tfrc gene was RA responsive, with a RA
      responsive element, and could be up regulated by RA in spermatogonial stem cell
      (SSC) line. Taken together, the results provide an important reference profile
      for further functional study of meiosis initiation. BIOLOGICAL SIGNIFICANCE:
      Spermatogenesis involves mitosis of spermatogonia, meiosis of spermatocytes and
      spermiogenesis, in which meiosis is a unique event to germ cells, and not in the
      somatic cells. Till now, the detailed molecular mechanisms of the transition from
      mitosis to meiosis are still not elucidated. With high-throughput proteomic
      technology, it is now possible to systemically identify proteins possibly
      involved. With TMT-6plex based quantification, we identified 104 proteins
      differentially between testes without meiosis (day 8.5) and those that were
      meiosis initiated (day 10.5). And a well-known protein essential for meiosis
      initiation, stra8, was identified to be differentially expressed in the study.
      And bioinformatic analysis and functional studies revealed several proteins
      regulated by retinoic acid, a chemical known to regulate the meiosis initiation.
      Thus, this quantitative proteomic approach can identify meiosis initiation
      regulating proteins, and further functional studies of these proteins will help
      elucidate the mechanisms of meiosis initiation.

PMID- 25753126
TI  - Margaret McCartney: Patients and professionals: all in this together?

PMID- 25753127
TI  - Quantum yield regeneration: influence of neutral ligand binding on photophysical
      properties in colloidal core/shell quantum dots.
AB  - This article describes an experiment designed to identify the role of specific
      molecular ligands in maintaining the high photoluminescence (PL) quantum yield
      (QY) observed in as-synthesized CdSe/CdZnS and CdSe/CdS quantum dots (QDs).
      Although it has been possible for many years to prepare core/shell quantum dots
      with near-unity quantum yield through high-temperature colloidal synthesis,
      purification of such colloidal particles is frequently accompanied by a reduction
      in quantum yield. Here, a recently established gel permeation chromatography
      (GPC) technique is used to remove weakly associated ligands without a change in
      solvent: a decrease in ensemble QY and average PL lifetime is observed. Minor
      components of the initial mixture that were removed by GPC are then added
      separately to purified QD samples to determine whether reintroduction of these
      components can restore the photophysical properties of the initial sample. We
      show that among these putative ligands trioctylphosphine and cadmium oleate can
      regenerate the initial high QY of all samples, but only the "L-type" ligands
      (trioctyphosphine and oleylamine) can restore the QY without changing the shapes
      of the optical spectra. On the basis of the PL decay analysis, we confirm that
      quenching in GPC-purified samples and regeneration in ligand-introduced samples
      are associated chiefly with changes in the relative population fraction of QDs
      with different decay rates. The reversibility of the QY regeneration process has
      also been studied; the introduction and removal of trioctylphosphine and
      oleylamine tend to be reversible, while cadmium oleate is not. Finally,
      isothermal titration calorimetry has been used to study the relationship between
      the binding strength of the neutral ligands to the surface and photophysical
      property changes in QD samples to which they are added. 

PMID- 25753128
TI  - Glial pathology in bipolar disorder: potential therapeutic implications.
AB  - Bipolar disorder (BD) is a chronic and severe mental disorder with recurrent
      episodes of mania and depression. In addition to neuronal alterations,
      accumulating evidences have revealed the importance of glial system in
      pathophysiology and phenotype of the illness. Postmortem studies have repeatedly
      demonstrated the alterations in glial cells and its functions in patients with
      BD. The activated microglia and inflammatory cytokines are proposed to be the
      potential biomarkers that may help to predict disease exacerbation in BD. On the
      other hand, anti-BD drugs have been shown to produce profound effects on glial
      activity, which not only contributes to the therapeutic efficacy, but may also
      provide a potential target for the drug development of BD. We will focus on the
      recent development of glial abnormalities and potential therapeutic benefits
      targeted to glial modulation in BD.

PMID- 25753129
TI  - A fluorinated detergent for membrane-protein applications.
AB  - Surfactants carrying fluorocarbon chains hold great promise as gentle
      alternatives to conventional hydrocarbon-based detergents for the solubilization
      and handling of integral membrane proteins. However, their inertness towards
      lipid bilayer membranes has limited the usefulness of fluorinated surfactants in
      situations where detergent-like activity is required. We demonstrate that
      fluorination does not necessarily preclude detergency, as exemplified by a
      fluorinated octyl maltoside derivative termed F6 OM. This nonionic compound
      readily interacts with and completely solubilizes phospholipid vesicles in a
      manner reminiscent of conventional detergents without, however, compromising
      membrane order at subsolubilizing concentrations. Owing to this mild and unusual
      mode of detergency, F6 OM outperforms a lipophobic fluorinated surfactant in
      chaperoning the functional refolding of an integral membrane enzyme by promoting
      bilayer insertion in the absence of micelles. 

PMID- 25753130
TI  - Lipopolysaccharide-binding protein cannot independently predict type 2 diabetes
      mellitus: A nested case-control study.
AB  - BACKGROUND: Cross-sectional studies have reported a close association between
      serum lipopolysaccharide-binding protein (LBP) and many metabolic disorders.
      However, no longitudinal study has explored the relationship between LBP and type
      2 diabetes mellitus (T2DM). The aim of the present study was to investigate the
      association between serum LBP levels and the risk of developing T2DM. METHODS: A
      5-year nested case-control study of 3510 individuals was performed as part of the
      Environment, Inflammation and Metabolic Diseases Study (EIMDS). Clinical data
      were collected at baseline. Serum levels of LBP and other biochemical factors,
      such as insulin and high-sensitivity C-reactive protein, were detected 5 years
      later. Subjects were diagnosed as having T2DM on the basis of results of an oral
      glucose tolerance test (OGTT) and 1998 World Health Organization criteria.
      Controls were randomly selected to match cases according to age, gender, and body
      mass index (BMI) in a 1:1 ratio. Odds ratios (OR) for T2DM were calculated using
      conditional logistic regression analysis. RESULTS: Over a 5-year follow-up
      period, 255 subjects developed T2DM. There was no significant difference in serum
      LBP levels between the T2DM and control groups at baseline (19.78 +/- 6.40 versus
      20.53 +/- 6.99 MUg/mL; P = 0.207). Subjects were divided into three groups based
      on tertiles of LBP concentrations (n = 170 in each group; T1 = 1.31-17.16 MUg/mL
      LBP; T2 = 17.21-22.37 MUg/mL LBP; T3 = 22.49-40.08 MUg/mL LBP). There was no
      significant association between the risk of developing T2DM and any of the LBP
      tertiles in either a simple model or after adjusting for general status and
      biochemical factors. CONCLUSION: After matching for gender, age, and BMI, LBP
      does not improve prediction of the development of T2DM independently.

PMID- 25753131
TI  - Explaining rigid dieting in normal-weight women: the key role of body image
      inflexibility.
AB  - Restrictive dieting is an increasing behavior presented by women in modern
      societies, independently of their weight. There are several known factors that
      motivate diet, namely a sense of dissatisfaction with one's body and unfavorable
      social comparisons based on physical appearance. However, dieting seems to have a
      paradoxical effect and has been considered a risk factor for weight gain and
      obesity in women and for maladaptive eating. Nevertheless, the study of the
      emotional regulation processes that explain the adoption of inflexible and rigid
      eating behaviors still remains little explored. In this line, the present study
      aims to explore why normal-weight women engage in highly rigid and inflexible
      diets. We hypothesize that body and weight dissatisfaction and unfavorable social
      comparisons based on physical appearance explain the adoption of inflexible
      eating rules, through the mechanisms of body image inflexibility. The current
      study comprised 508 normal-weight female college students. Path analyses were
      conducted to explore the study's hypotheses. Results revealed that the model
      explained 43 % of inflexible eating and revealed excellent fit indices.
      Furthermore, the unwillingness to experience unwanted events related to body
      image (body image inflexibility) mediated the impact of body dissatisfaction and
      unfavorable social comparisons on the adoption of inflexible eating rules. This
      study highlights the relevance of body image inflexibility to explain rigid
      eating attitudes, and it seems to be an important avenue for the development of
      interventions focusing on the promotion of adaptive attitudes towards body image
      and eating in young women. 

PMID- 25753132
TI  - Photothermal cellular stimulation in functional bio-polymer interfaces.
AB  - Hybrid interfaces between organic semiconductors and living tissues represent a
      new tool for in-vitro and in-vivo applications, bearing a huge potential, from
      basic researches to clinical applications. In particular, light sensitive
      conjugated polymers can be exploited as a new approach for optical modulation of
      cellular activity. In this work we focus on light-induced changes in the membrane
      potential of Human Embryonic Kidney (HEK-293) cells grown on top of a poly(3
      hexylthiophene) (P3HT) thin film. On top of a capacitive charging of the polymer
      interface, we identify and fully characterize two concomitant mechanisms, leading
      to membrane depolarization and hyperpolarisation, both mediated by a thermal
      effect. Our results can be usefully exploited in the creation of a new platform
      for light-controlled cell manipulation, with possible applications in
      neuroscience and medicine. 

PMID- 25753133
TI  - Clinical characteristics and survival outcomes of super-elderly hepatocellular
      carcinoma patients not indicated for surgical resection.
AB  - AIM: Considering the dramatic increase in average life expectancy during the 20th
      century throughout the world, the management of elderly patients with cancer has
      become a global issue. We herein investigated the clinical characteristics and
      outcomes of super-elderly hepatocellular carcinoma (HCC) patients over 80 years
      old not indicated for surgical resection. METHODS: We retrospectively evaluated
      206 newly diagnosed HCC patients. The patients were divided into two groups
      according to their age at inclusion; a super-elderly group (n = 37, >=80 years)
      and a younger group (n = 169, <80 years). We compared the clinical
      characteristics, overall survival (OS) and disease-specific survival (DSS) rates
      among the two groups. Both univariate and multivariate analyses were performed to
      identify the factors associated with the OS and DSS. RESULTS: The proportion of
      women was higher in the super-elderly group than in the younger group (P =
      0.017). There were no significant differences in the OS (P = 0.171) or DSS (P =
      0.176) between the two groups. The multivariate analysis revealed that only the
      Cancer Liver Italian Program score (hazard ratio [HR], 2.972; P < 0.0001; HR,
      3.694; P < 0.0001) was independently associated with the OS and DSS. Age was not
      found to be associated with the OS or DSS according to either the univariate or
      multivariate analysis. CONCLUSION: There were no significant differences in the
      OS and DSS rates among the super-elderly HCC patients and younger HCC patients
      not indicated for surgical resection. An advanced age itself does not restrict
      the therapeutic approach, even in super-elderly HCC patients not indicated for
      surgical resection.

PMID- 25753134
TI  - P53-Mediated Repression of the Reprogramming in Cloned Bovine Embryos Through
      Direct Interaction with HDAC1 and Indirect Interaction with DNMT3A.
AB  - P53 is a transcriptional activator, regulating growth arrest, DNA repair and
      apoptosis. We found that the expression level of P53 and the epigenetic profiles
      were significantly different in bovine somatic cell nuclear transfer embryos from
      those in vitro fertilization (IVF) embryos. So we inferred that abnormally
      expression of P53 might contribute to the incomplete reprogramming. Using bovine
      foetal fibroblasts, we constructed and screened a highly efficient shRNA vector
      targeting bovine P53 gene and then reconstituted somatic cell nuclear transfer
      embryos (RNAi-SCNT). The results indicated that expression levels of P53 were
      downregulated significantly in RNAi-SCNT embryos, and the blastulation rate and
      the total number of cell increased significantly. Moreover, methylation levels of
      CpG islands located 5' region of OCT4, NANOG, H19 and IGF2R in RNAi -SCNT embryos
      were significantly normalized to that IVF embryos, and the methylation levels of
      genome DNA, H3K9 and H4K5 acetylation levels were also returned to levels similar
      to the IVF embryos. Differentially expressed genes were identified by microarray,
      and 28 transcripts were found to be significantly different (> twofolds) in RNAi
      SCNT embryos compared to the control nuclear transfer embryos (SCNT). Among the
      28 differentially expressed transcripts, just HDAC1 and DNMT3A were closely
      associated with the epigenetic modifications. Finally, ChIP further showed that
      P53 might repress the epigenetic reprogramming by regulating HDAC1 directly and
      DNMT3A indirectly. These findings offer significant references to further
      elucidate the mechanism of epigenetic reprogramming in SCNT embryos. 

PMID- 25753135
TI  - Cough and wheeze events are temporally associated with increased pain in
      individuals with sickle cell disease without asthma.

PMID- 25753136
TI  - Benefits of a fixed-dose combination of bisoprolol and amlodipine in the
      treatment of hypertension in daily practice: results of more than 4000 patients.
AB  - OBJECTIVE: The study objective was assessing patient adherence to a fixed-dose
      combination (FDC) of bisoprolol and amlodipine in daily practice in patients who
      had been switched from the free to the fixed-dose combination prior to
      recruitment. MATERIAL AND METHODS: The non-investigational study was carried out
      in Poland. Patients over 18 years of age with essential hypertension were
      recruited if they had already been switched from a free combination to the FDC at
      least 4 weeks prior to recruitment. Exclusion criteria included pregnancy,
      lactation, any contraindication to the FDC, and other antihypertensive treatment.
      Adherence was measured by tablet count (tablets taken divided by tablets
      prescribed, times 100) and defined as follows: excellent >90%, good 76-90%,
      moderate 51-75%, bad <=50%. Other patient data, clinical findings and laboratory
      values were recorded upon availability at study start, after 3 months (voluntary)
      and after 6 months. RESULTS: Data of 4288 patients (mean age: 59 years; gender:
      50% each) were documented. The average daily doses of the FDC were 5.8 mg
      bisoprolol and 6.4 mg amlodipine. These doses differ only slightly from those of
      the free combination. After 3 months' treatment with the FDC, a dose increase was
      carried out in 113 patients for bisoprolol and in 126 for amlodipine. After 6
      months of FDC treatment, 82% of the participants of the study showed excellent
      adherence and for a further 15% the adherence could be considered good. This
      strong adherence may have led to the observed reduction in systolic and diastolic
      blood pressure of 11% (Cohen's D efficient size 1.23). In addition, pulse
      pressure decreased from 58.8 mm to 52.2 mm. Also in diabetic patients (21% of the
      cohort), further reduction of systolic blood pressure values could be achieved
      (mean before 150 mm, after 133), wherein the initial differences compared to
      patients without diabetes had disappeared. The pulse rate also changed from 75
      b/min to 68 b/min under the FDC. CONCLUSION: These study results clearly show
      that the FDC leads to excellent patient adherence and therefore may result in
      better blood pressure control. Blood pressure control is crucial in the risk
      reduction of cardiovascular events. The key limitation of this study is that the
      study design does not allow a direct comparison of patient adherence under the
      free and the fixed-dose combination.

PMID- 25753137
TI  - Blood culture-based diagnosis of bacteraemia: state of the art.
AB  - Blood culture remains the best approach to identify the incriminating
      microorganisms when a bloodstream infection is suspected, and to guarantee that
      the antimicrobial treatment is adequate. Major improvements have been made in the
      last years to increase the sensitivity and specificity and to reduce the time to
      identification of microorganisms recovered from blood cultures. Among other
      factors, the introduction in clinical microbiology laboratories of the matrix
      assisted laser desorption ionization time-of-flight mass spectrometry technology
      revolutionized the identification of microorganisms whereas the introduction of
      nucleic-acid-based methods, such as DNA hybridization or rapid PCR-based test,
      significantly reduce the time to results. Together with traditional antimicrobial
      susceptibility testing, new rapid methods for the detection of resistance
      mechanisms respond to major epidemiological concerns such as methicillin
      resistant Staphylococcus aureus, extended-spectrum beta-lactamase or
      carbapenemases. This review presents and discusses the recent developments in
      microbial diagnosis of bloodstream infections based on blood cultures. 

PMID- 25753138
TI  - Systematic review: noncoeliac gluten sensitivity.
AB  - BACKGROUND: Noncoeliac gluten sensitivity (NCGS) is a controversial emerging
      disorder. Despite reported symptoms related to the ingestion of gluten, NCGS
      remains a diagnosis based on the exclusion of coeliac disease, given the absence
      of reliable biomarkers. AIM: To evaluate the prevalence, diagnostic exclusion of
      coeliac disease and the efficacy of a gluten-free diet (GFD) for NCGS patients.
      METHODS: A PubMed search was performed up to December 2014. According to
      consensus diagnostic criteria, NCGS was defined as self-reported gluten
      intolerance, negative coeliac serology and absence of villous atrophy. Studies
      evaluating the impact of a GFD on patients with irritable bowel syndrome (IBS)
      were also included. RESULTS: Prevalence rates of NCGS (0.5-13%) differed widely.
      Seventeen studies, including 1561 patients (26 children), met the inclusion
      criteria for NCGS. HLA haplotypes could not be linked to histology [normal or
      lymphocytic enteritis (LE)] in 1123 NCGS patients. HLADQ2/DQ8 haplotypes were
      present in 44% of NCGS patients. After advanced diagnostic techniques in 189 NCGS
      patients combining LE and HLADQ2/DQ8 haplotypes, 39 (20%) were reclassified as
      coeliac disease. There was a higher than expected family history of coeliac
      disease and autoimmune disorders in NCGS patients. A GFD resulted in variable
      results for variable, but significantly improved stool frequency in HLADQ2
      positive diarrhoea-predominant IBS patients. CONCLUSIONS: Prevalence rates for
      NCGS are extremely variable. A subset of NCGS patients might belong in the so
      called 'coeliac-lite' disease. The benefit of a GFD for NCGS patients is
      currently controversial. HLADQ2 positive diarrhoea-type IBS patients might gain
      symptom improvement from a GFD.

PMID- 25753139
TI  - Implementation of evidence-based dentistry into practice: analysis of awareness,
      perceptions and attitudes of dentists in the World Dental Federation-European
      Regional Organization zone.
AB  - Based on evidence-based dentistry (EBD) being a relatively new concept in
      dentistry, the attitudes, perceptions and level of awareness of dentists
      regarding EBD, and perceived barriers to its implementation into daily practice,
      were comparatively analysed in six countries of the FDI (World Dental Federation
      Federation Dentaire Internationale)-European Regional Organization (ERO) zone
      (France, Georgia, Poland, Portugal, Slovakia and Turkey). For this purpose, a
      questionnaire, 'The Relationship Between Dental Practitioners and Universities',
      was developed by the FDI-ERO Working Group and applied by National Dental
      Associations (NDAs). A total of 850 valid responses were received, and cumulative
      data, comparisons between countries and potential impact of demographic variables
      were analysed. Regarding EBD, similar percentages of respondents reported that
      they 'know what it is' (32.8%) and 'they practice' (32.1%). Most respondents
      believed that 'EBD is beneficial' (89.1%); however, they had different thoughts
      regarding 'who actually benefited from EBD'. Of the participants, 60% believed
      that 'dentists experience difficulties in implementing EBD'. Although lack of
      time, lack of education and limited availability of evidence-based clinical
      guidelines were among the major barriers, there were differences among countries
      (P<0.05). Significant differences were also observed between countries regarding
      certain questions such as 'where EBD needed to be taught' (P<0.05), as both
      undergraduate and continuing education were suggested to be suitable. Age,
      practice mode and years of practice significantly affected many of the responses
      (P<0.05). There was a general, positive attitude toward EBD; however, there was
      also a clear demand for more information and support to enhance dentists'
      knowledge and use of EBD in everyday practice and a specific role for the NDAs.

PMID- 25753140
TI  - Mycosis fungoides: association of KIR ligands and HLA-DQB1*05 with bad prognosis
      of the disease.
AB  - BACKGROUND: Mycosis fungoides (MF) is the most common cutaneous T-cell lymphoma.
      We previously reported that the prognosis of MF patients is not only related on
      clinical variables but it is also associated with peculiar HLA alleles. Until
      today, the association of HLA ligands for KIR with the prognosis of the disease
      has not yet been analysed. OBJECTIVE: We investigated the frequency of HLA
      ligands for killer cell Immunoglobulin-like receptors (KIRs) in MF patients,
      evaluating if the presence of particular HLA alleles that are ligands for KIR may
      have prognostic value. METHODS: The study includes 46 Caucasian MF patients that,
      between 1993 and 1997, underwent HLA genomic typing. All patients were diagnosed
      and followed up from 1977 to 2012 (mean follow-up of 11 years). RESULTS: MF
      patients have been divided into two groups (long survivors and dead patients). We
      noticed that the HLA-Bw6/Bw6 specificity increased among the group of seven dead
      patients compared to the group of 39 long survivors (71.4% vs. 41.0%, P = ns, OR
      = 3.59), while in the long survivors group the HLA- Bw4/Bw4 specificity increased
      when compared to dead patients (23.0% vs. 0%, P = ns). Moreover, we observed that
      six of the seven dead patients had HLA-DQB1*05; the phenotypic frequency of this
      HLA allele, in dead and long survivors patients, was 85.7% and 23.0% respectively
      (P = 0.004; OR = 20). CONCLUSION: Our observations suggest that the presence of
      the HLA-DQB1*05 alleles characterizes the patients with the poorest prognosis in
      MF. In addition, absence of the KIR-ligand epitope HLA-B Bw4 showed a trend of
      being more prominent in MF patients with the poorest prognosis.

PMID- 25753141
TI  - Capillary zone electrophoresis method for the direct determination of amino acids
      in recombinant human erythropoietin preparations used for the treatment of
      anemia.
AB  - A method based on CZE for the determination of glutamic acid, glycine, and
      alanine in a biopharmaceutical formulation containing recombinant human
      erythropoietin was developed. The separation was achieved within less than 5 min,
      using a fused-silica capillary column (55 cm * 50 MUm id) and 30 mmol/L phosphate
      buffer at pH 11.5, containing 0.6 mmol/L CTAB and 10% v/v methanol, as BGE
      solution. Applied potential of -25 kV, temperature of 15 degrees C and
      hydrodynamic injection time of 15 s, at 50 mbar, were employed. The detection of
      the analytes was carried out without any derivatization reaction, at 220 nm using
      an UV-DAD detector. Linear ranges from 50 to 2500 mg/L and quantification limits
      of 40, 39, and 37 mg/L were obtained for glutamic acid, glycine, and alanine,
      respectively. Sample preparation required only a dilution step. Considering peak
      area and migration time values, the method presented good repeatability (RSD
      <1.7%; n = 9) and intermediate precision (RSD <1.0%; n = 6). Recovery evaluation
      using a commercial sample led to values between 97.5 +/- 5.2% and 101.5 +/- 4.6%,
      demonstrating the feasibility of the method, which was successfully applied in
      the quantification of the amino acids of interest in biopharmaceutical samples. 

PMID- 25753142
TI  - Accuracy of continuous noninvasive hemoglobin monitoring for the prediction of
      blood transfusions in trauma patients.
AB  - Early detection of hemorrhagic shock is required to facilitate prompt
      coordination of blood component therapy delivery to the bedside and to expedite
      performance of lifesaving interventions. Standard physical findings and vital
      signs are difficult to measure during the acute resuscitation stage, and these
      measures are often inaccurate until patients deteriorate to a state of
      decompensated shock. The aim of this study is to examine a severely injured
      trauma patient population to determine whether a noninvasive SpHb monitor can
      predict the need for urgent blood transfusion (universal donor or additional
      urgent blood transfusion) during the first 12 h of trauma patient resuscitation.
      We hypothesize that trends in continuous SpHb, combined with easily derived
      patient-specific factors, can identify the immediate need for transfusion in
      trauma patients. Subjects were enrolled if directly admitted to the trauma
      center, >17 years of age, and with a shock index (heart rate/systolic blood
      pressure) >0.62. Upon admission, a Masimo Radical-7 co-oximeter sensor (Masimo
      Corporation, Irvine, CA) was applied, providing measurement of continuous non
      invasive hemoglobin (SpHb) levels. Blood was drawn and hemoglobin concentration
      analyzed and conventional pulse oximetry photopletysmograph signals were
      continuously recorded. Demographic information and both prehospital and admission
      vital signs were collected. The primary outcome was transfusion of at least one
      unit of packed red blood cells within 24 h of admission. Eight regression models
      (C1-C8) were evaluated for the prediction of blood use by comparing area under
      receiver operating curve (AUROC) at different time intervals after admission. 711
      subjects had continuous vital signs waveforms available, to include heart rate
      (HR), SpHb and SpO2 trends. When SpHb was monitored for 15 min, SpHb did not
      increase AUROC for prediction of transfusion. The highest ROC was recorded for
      model C8 (age, sex, prehospital shock index, admission HR, SpHb and SpO2) for the
      prediction of blood products within the first 3 h of admission. When data from 15
      min of continuous monitoring were analyzed, significant improvement in AUROC
      occurred as more variables were added to the model; however, the addition of SpHb
      to any of the models did not improve AUROC significantly for prediction of blood
      use within the first 3 h of admission in comparison to analysis of conventional
      oximetry features. The results demonstrate that SpHb monitoring, accompanied by
      continuous vital signs data and adjusted for age and sex, has good accuracy for
      the prediction of need for transfusion; however, as an independent variable, SpHb
      did not enhance predictive models in comparison to use of features extracted from
      conventional pulse oximetry. Nor was shock index better than conventional
      oximetry at discriminating hemorrhaging and prediction of casualties receiving
      blood. In this population of trauma patients, noninvasive SpHb monitoring,
      including both trends and absolute values, did not enhance the ability to predict
      the need for blood transfusion.

PMID- 25753143
TI  - Appearance of an electrocardiogram tracing on a bispectral index monitor with
      plausible BIS values.

PMID- 25753144
TI  - Evaluation of the MicrostatTM sublingual PCO2 monitor in ambulatory patients.
AB  - Physicians often need to measure arterial PCO2 in clinical practice. Arterial
      blood gas sampling is typically available only in hospitals and may be unpleasant
      for patients. Minimally invasive techniques for measuring PCO2 offer the
      potential for overcoming these limitations. The MicroStat monitor non-invasively
      measures PCO2 in the sublingual tissues, which should track arterial PCO2 in
      hemodynamically stable patients. This was a prospective observational study.
      Patients undergoing routine cardiac catheterization were recruited. Following
      arterial cannulation, two sequential sublingual PCO2 measurements were taken and
      a contemporaneous arterial sample was sent for blood gas analysis. For each
      subject we calculated the mean sublingual-arterial CO2 gradient and the test
      retest sublingual PCO2 difference. Twenty-five patients were studied. Mean
      sublingual-arterial PCO2 gradient was +6.8 mmHg (95 % limits of agreement -3.0 to
      16.6 mmHg). Test-retest difference was 3.4 mmHg (95 % limits of agreement -1.1 to
      7.9 mmHg), p = 0.11 (Wilcoxon test), repeatability was 11 mmHg. The MicroStat
      sublingual PCO2 monitor over-estimates arterial PCO2 with wide limits of
      agreement. Test-retest repeatability was poor. Use of sublingual PCO2 monitoring
      with the MicroStat monitor cannot currently replace blood gas sampling. 

PMID- 25753145
TI  - GATA3 expression in gestational trophoblastic tissues and tumours.
AB  - AIMS: GATA3 is a zinc-finger transcription factor that is important for
      trophoblast differentiation. GATA3 is sensitive for urothelial and breast
      carcinomas, but the specificity is low. The aim of this study was to investigate
      the expression of GATA3 in trophoblast-related tissues and neoplasia. METHODS AND
      RESULTS: GATA3 immunohistochemistry was performed on 33 placentas, one atypical
      placental site nodule, 25 hydatidiform moles (HMs), and 13 gestational
      trophoblastic tumours (GTTs). One hundred and sixty endometrial adenocarcinomas
      were also stained. Western blotting was performed on trophoblastic cell lines and
      compared to other cancer cell lines. Immature placentas were characterized by
      strong, diffuse nuclear GATA3 staining. Mature placentas showed less expression
      with scattered positive cells in the villous cytotrophoblast. HMs showed diffuse
      expression in cytotrophoblast and implantation site trophoblast, and
      heterogeneous expression in extravillous trophoblast. All GTTs were positive for
      GATA3. All endometrial adenocarcinomas were GATA3-negative. Western blotting
      demonstrated GATA3 in choriocarcinoma, whereas the placenta, and cervical and
      endometrial cancer cell lines, were negative. CONCLUSIONS: All trophoblast
      lineages were positive for GATA3. The extent of GATA3 expression varied between
      immature and mature placentas, suggesting a role in trophoblast maturation. GATA3
      does not distinguish normal placenta, HMs, or GTTs. Nevertheless, GATA3 may help
      in distinguishing trophoblastic tumors from Mullerian epithelial malignancies and
      a subset of tumours of unknown origin.

PMID- 25753146
TI  - Promising behavior change techniques in a multicomponent intervention to reduce
      concerns about falls in old age: a Delphi study.
AB  - Complex behavior change interventions need evidence regarding the effectiveness
      of individual components to understand how these interventions work. The
      objective of this study was to identify the least and most promising behavior
      change techniques (BCTs) within the Dutch intervention 'A Matter of Balance' (AMB
      NL) aimed at concerns about falls in old age as an example. After the
      identification of 27 BCTs within AMB-NL, an online two-round Delphi survey among
      16 international experts was conducted to reach consensus on the least and most
      promising BCTs. The level of consensus and the level of importance of BCTs were
      determined. In total, 23 of the 27 (>85%) BCTs identified reached consensus. Most
      promising BCTs were goal setting (behavior), graded tasks and behavioral
      practice/rehearsal. Information about health consequences, salience of
      consequences and information about emotional consequences were considered least
      promising. These outcomes provide a first but important step in the evidence
      building process regarding the effectiveness of BCTs in a complex intervention. 

PMID- 25753148
TI  - Endothelin-receptor antagonists for diabetic nephropathy: A meta-analysis.
AB  - AIM: Endothelin-receptor antagonists may be a novel therapeutic strategy for
      diabetic nephropathy, but their use remains controversial. This meta-analysis
      seeks to evaluate the effectiveness and safety of endothelin-receptor antagonists
      for patients with diabetic nephropathy. METHODS: Literature reviews of the
      PubMed, EMBASE and CENTRAL databases were conducted to identify randomized
      controlled trials (RCTs) comparing endothelin-receptor antagonist treatment with
      placebo in patients with diabetic nephropathy. Quality assessment was performed
      by using the Cochrane Handbook's tools for assessing risk of bias; meta-analysis
      was conducted by RevMan 5.3. RESUTLS: Five RCTs (n=2034 patients) were included
      for analysis. Compared with placebo, endothelin-receptor antagonists showed
      significant benefits for lowering albuminuria (five trials, n=2034 patients; SMD
      0.66 95% confidence interval (CI) 0.56 to 0.76), but there was no significant
      difference in the risk of death (two trials, n=1674 patients; RR 1.49 95% CI 0.81
      to 2.76). In addition, risk of cardiovascular events and other serious adverse
      events were significantly higher in the endothelin-receptor antagonists group
      than the placebo group (four trials, n=1956 patients; RR 1.45 95% CI 1.07 to
      1.97; five trials, n=2034 patients; RR 1.32 95% CI 1.10 to 1.58). CONCLUSION:
      Endothelin-receptor antagonists can reduce albuminuria in patients with diabetic
      nephropathy, although use resulted in more serious adverse events compared with
      placebo. There is a potential need for further RCTs, which has larger sample size
      and longer duration.

PMID- 25753147
TI  - Keratinocyte p38delta loss inhibits Ras-induced tumor formation, while systemic
      p38delta loss enhances skin inflammation in the early phase of chemical
      carcinogenesis in mouse skin.
AB  - p38delta expression and/or activity are increased in human cutaneous
      malignancies, including invasive squamous cell carcinoma (SCC) and head and neck
      SCC, but the role of p38delta in cutaneous carcinogenesis has not been well
      defined. We have reported that mice with germline loss of p38delta exhibited a
      reduced susceptibility to skin tumor development compared with wild-type mice in
      the two-stage 7,12-dimethylbenz(a)anthracene (DMBA)/12-O-tetradecanoylphorbol-13
      acetate (TPA) chemical skin carcinogenesis model. Here, we report that p38delta
      gene ablation inhibited the growth of tumors generated from v-ras(Ha) 
      transformed keratinocytes in skin orthografts to nude mice, indicating that
      keratinocyte-intrinsic p38delta is required for Ras-induced tumorigenesis. Gene
      expression profiling of v-ras(Ha) -transformed p38delta-null keratinocytes
      revealed transcriptional changes associated with cellular responses linked to
      tumor suppression, such as reduced proliferation and increased differentiation,
      cell adhesion, and cell communications. Notably, a short-term DMBA/TPA challenge,
      modeling the initial stages of chemical skin carcinogenesis treatment, elicited
      an enhanced inflammation in p38delta-null skin compared with skin of wild-type
      mice, as assessed by measuring the expression of pro-inflammatory cytokines,
      including IL-1beta, IL-6, IL-17, and TNFalpha. Additionally, p38delta-null skin
      and p38delta-null keratinocytes exhibited increased p38alpha activation and
      signaling in response to acute inflammatory challenges, suggesting a role for
      p38alpha in stimulating the elevated inflammatory response in p38delta-null skin
      during the initial phases of the DMBA/TPA treatment compared with similarly
      treated p38delta(+/+) skin. Altogether, our results indicate that p38delta
      signaling regulates skin carcinogenesis not only by keratinocyte cell-autonomous
      mechanisms, but also by influencing the interaction between between the
      epithelial compartment of the developing skin tumor and its stromal
      microenvironment.

PMID- 25753149
TI  - Antibacterial properties and atomic resolution X-ray complex crystal structure of
      a ruthenocene conjugated beta-lactam antibiotic.
AB  - We have determined a 1.18 A resolution X-ray crystal structure of a novel
      ruthenocenyle-6-aminopenicillinic acid in complex with CTX-M beta-lactamase,
      showing unprecedented details of interactions between ruthenocene and protein. As
      the first product complex with an intact catalytic serine, the structure also
      offers insights into beta-lactamase catalysis and inhibitor design. 

PMID- 25753150
TI  - Transition-metal-free coupling reaction of vinylcyclopropanes with aldehydes
      catalyzed by tin hydride.
AB  - Donor-acceptor cyclopropanes are useful building blocks for catalytic
      cycloaddition reactions with a range of electrophiles to give various cyclic
      products. In contrast, relatively few methods are available for the synthesis of
      homoallylic alcohols through coupling of vinylcyclopropanes (VCPs) with
      aldehydes, even with transition-metal catalysts. Here, we report that the
      hydrostannation of vinylcyclopropanes (VCPs) was effectively promoted by
      dibutyliodotin hydride (Bu2 SnIH). The resultant allylic tin compounds reacted
      easily with aldehydes. Furthermore, the use of Bu2 SnIH was effectively catalytic
      in the presence of hydrosilane as a hydride source, which established a coupling
      reaction of VCPs with aldehydes for the synthesis of homoallylic alcohols without
      the use of transition-metal catalysts. In contrast to conventional catalytic
      reactions of VCPs, the presented method allowed the use of several VCPs in
      addition to conventional donor-acceptor cyclopropanes. 

PMID- 25753151
TI  - Erratum to: Neighborhoods of trees in circular orderings.

PMID- 25753152
TI  - Prevalence and determinants of declining versus stable hemoglobin levels in whole
      blood donors.
AB  - BACKGROUND: A too short recovery time after blood donation results in a gradual
      depletion of iron stores and a subsequent decline in hemoglobin (Hb) levels over
      time. This decline in Hb levels may depend on individual, unobserved
      characteristics of the donor. STUDY DESIGN AND METHODS: We used a data set of
      5388 Dutch blood donors from the Donor InSight study. The statistical analysis is
      based on a Bayesian growth mixture model, which assumes that each donor belongs
      to one of several groups. Each group implies a different Hb trajectory, and
      donors with similar longitudinal trajectories belong to the same group. Analyses
      were performed for male and female donors separately. RESULTS: For both sexes the
      model identified four groups of donors. Stable Hb trajectories were found among
      14% of male donors and 15% of female donors; declining Hb trajectories were
      observed in the remaining groups of donors. The percentage of donor deferrals
      differed strongly between groups. CONCLUSION: The model can be used to predict to
      which group a donor belongs, and this prediction can be updated after each
      donation. This is of high practical importance because early identification of
      donors with declining Hb levels could help to tailor donation intervals and to
      prevent iron deficiency and donor deferrals.

PMID- 25753153
TI  - The trouble with quality filtering based on relative Cramer-Rao lower bounds.
AB  - Cramer Rao Lower Bounds (CRLB) have become the standard for expression of
      uncertainties in quantitative MR spectroscopy. If properly interpreted as a lower
      threshold of the error associated with model fitting, and if the limits of its
      estimation are respected, CRLB are certainly a very valuable tool to give an idea
      of minimal uncertainties in magnetic resonance spectroscopy (MRS), although other
      sources of error may be larger. Unfortunately, it has also become standard
      practice to use relative CRLB expressed as a percentage of the presently
      estimated area or concentration value as unsupervised exclusion criterion for bad
      quality spectra. It is shown that such quality filtering with widely used
      threshold levels of 20% to 50% CRLB readily causes bias in the estimated mean
      concentrations of cohort data, leading to wrong or missed statistical findings-
      and if applied rigorously--to the failure of using MRS as a clinical instrument
      to diagnose disease characterized by low levels of metabolites. Instead, absolute
      CRLB in comparison to those of the normal group or CRLB in relation to normal
      metabolite levels may be more useful as quality criteria.

PMID- 25753154
TI  - Luminescent difluoroboron beta-diketonate PEG-PLA oxygen nanosensors for tumor
      imaging.
AB  - Surface modification of nanoparticles and biosensors is a dynamic, expanding area
      of research for targeted delivery in vivo. For more efficient delivery, surfaces
      are PEGylated to impart stealth properties, long circulation, and enable enhanced
      permeability and retention (EPR) in tumor tissues. Previously, BF2 dbm(I)PLA was
      proven to be a good oxygen nanosensor material for tumor hypoxia imaging in vivo,
      though particles were applied directly to the tumor and surrounding region.
      Further surface modification is needed for this dual-emissive oxygen sensitive
      material for effective intravenous (IV) administration and passive and active
      delivery to tumors. In this paper, an efficient synthesis of a new dual-emissive
      material BF2 dbm(I)PLA-mPEG is presented and in vitro stability studies are
      conducted. It is found that fabricated nanoparticles are stable for 24 weeks as a
      suspension, while after 25 weeks the nanoparticles swell and both dye and polymer
      degradation escalates. Preliminary studies show BF2 dbm(I)PLA-mPEG nanoparticle
      accumulation in a window chamber mammary tumor 24 h after IV injection into mice
      (C57Bl/6 strain) enabling tumor oxygen imaging. 

PMID- 25753155
TI  - Critical role of the miR-200 family in regulating differentiation and
      proliferation of neurons.
AB  - The generation of differentiated and functional neurons is a complex process,
      which requires coordinated expression of several proteins and microRNAs (miRNAs).
      The present study using nerve growth factor (NGF)-differentiated PC12 cells led
      to the identification of miR-200, miR-221/222 and miR-34 families as major up
      regulated miRNAs in fully differentiated neurons. Similar to PC12 cells,
      induction of miR-200 family was observed in differentiating neural stem cells,
      demonstrating a direct role of miR-200 family in neuronal differentiation. Over
      expression of miR-200 induced neurite formation in PC12 cells and regulated
      neuronal markers in favour of differentiation. However, inhibition of miR-200
      induced proliferation of PC12 cells. In differentiating PC12 cells and neural
      stem cells, an inverse relationship was observed between expression of
      reprogramming transcription factors (SOX2, KLF4, NANOG, OCT4 and PAX6) and miR
      200. Over-expression of miR-200 in PC12 cells significantly down-regulated mRNA
      and protein levels of SOX2 and KLF4. Moreover, we observed two phases of dramatic
      down-regulation of miR-200 expression in developing rat brains correlating with
      periods of neuronal proliferation. In conclusion, our results indicate that
      increased expression of the miR-200 family promotes neuronal differentiation,
      while decreased expression of the miR-200 family promotes neuronal proliferation
      by targeting SOX2 and KLF4. 

PMID- 25753156
TI  - The siRNA cocktail targeting interleukin 10 receptor and transforming growth
      factor-beta receptor on dendritic cells potentiates tumour antigen-specific
      CD8(+) T cell immunity.
AB  - Dendritic cells (DCs) are promising therapeutic agents in the field of cancer
      immunotherapy due to their intrinsic immune-priming capacity. The potency of DCs,
      however, is readily attenuated immediately after their administration in patients
      as tumours and various immune cells, including DCs, produce various
      immunosuppressive factors such as interleukin (IL)-10 and transforming growth
      factor (TGF)-beta that hamper the function of DCs. In this study, we used small
      interfering RNA (siRNA) to silence the expression of endogenous molecules in DCs,
      which can sense immunosuppressive factors. Among the siRNAs targeting various
      immunosuppressive molecules, we observed that DCs transfected with siRNA
      targeting IL-10 receptor alpha (siIL-10RA) initiated the strongest antigen
      specific CD8(+) T cell immune responses. The potency of siIL-10RA was enhanced
      further by combining it with siRNA targeting TGF-beta receptor (siTGF-betaR),
      which was the next best option during the screening of this study, or the
      previously selected immunoadjuvant siRNA targeting phosphatase and tensin
      homologue deleted on chromosome 10 (PTEN) or Bcl-2-like protein 11 (BIM). In the
      midst of sorting out the siRNA cocktails, the cocktail of siIL-10RA and siTGF
      betaR generated the strongest antigen-specific CD8(+) T cell immunity.
      Concordantly, the knock-down of both IL-10RA and TGF-betaR in DCs induced the
      strongest anti-tumour effects in the TC-1 P0 tumour model, a cervical cancer
      model expressing the human papillomavirus (HPV)-16 E7 antigen, and even in the
      immune-resistant TC-1 (P3) tumour model that secretes more IL-10 and TGF-beta
      than the parental tumour cells (TC-1 P0). These results provide the groundwork
      for future clinical development of the siRNA cocktail-mediated strategy by co
      targeting immunosuppressive molecules to enhance the potency of DC-based
      vaccines. 

PMID- 25753157
TI  - MRI measurements of intracranial pressure in the upright posture: The effect of
      the hydrostatic pressure gradient.
AB  - PURPOSE: To add the hydrostatic component of the cerebrospinal fluid (CSF)
      pressure to magnetic resonance imaging (MRI)-derived intracranial pressure (ICP)
      measurements in the upright posture for derivation of pressure value in a central
      cranial location often used in invasive ICP measurements. MATERIALS AND METHODS:
      Additional analyses were performed using data previously collected from 10
      healthy subjects scanned in supine and sitting positions with a 0.5T vertical gap
      MRI scanner (GE Medical). Pulsatile blood and CSF flows to and from the brain
      were quantified using cine phase-contrast. Intracranial compliance and pressure
      were calculated using a previously described method. The vertical distance
      between the location of the CSF flow measurement and a central cranial location
      was measured manually in the mid-sagittal T1 -weighted image obtained in the
      upright posture. The hydrostatic pressure gradient of a CSF column with similar
      height was then added to the MR-ICP value. RESULTS: After adjustment for the
      hydrostatic component, the mean ICP value was reduced by 7.6 mmHg. Mean ICP
      referenced to the central cranial level was -3.4 +/- 1.7 mmHg compared to the
      unadjusted value of +4.3 +/- 1.8 mmHg. CONCLUSION: In the upright posture, the
      hydrostatic pressure component needs to be added to the MRI-derived ICP values
      for compatibility with invasive ICP at a central cranial location.

PMID- 25753159
TI  - Investigating the effects of treatment based on single high blood glucose in
      gestational diabetes screening on maternal and neonatal complications.
AB  - PURPOSE: To create a positive step toward achieving an efficient method for
      gestational diabetes treatment, the present study was carried out to compare the
      treatment outcomes based on single impaired blood glucose versus regular method
      in health care centers in Iran. METHODS: This randomized clinical trial was
      carried out in Tehran/Iran between March 2012 and August 2013. Study sample
      consisted of mothers whose fasting blood sugar was disturbed or a disturbed blood
      sugar was seen in OGTT with 75 g glucose load, according to ADA standards. For
      each outcome, multiple logistic regressions were used to control for the effects
      of potential confounders. When a confounder was measured on a continuous scale
      (e.g., age), LOWESS (locally weighted scatter plot smoothing) algorithm was used
      to determine whether the effect of that variable was linear. We also used the
      fractional polynomial regression to determine the optimal transformation of
      continuous covariates. RESULTS: The information of 189 pregnant women was used in
      this study; 87 in the interventional group (46 %) and 102 in the control group
      (54 %). Treatment based on the new protocol has very high protective effect (OR
      0.25, 95 % CI 0.68-0.88) in terms of neonatal hyperbilirubinemia. This difference
      was not seen in other outcomes including stillbirth, macrosomic newborn delivery,
      hypoglycemia, and hypocalcemia. The risk of neonatal hypoglycemia reduced after
      the 25th week of gestation (OR 0.39, 95 % CI 0.15-0.98). CONCLUSIONS: Although
      the treatment of mild gestational diabetes could not significantly decrease
      severe neonatal outcomes, it did significantly reduce the risk of
      hyperbilirubinemia and its subsequent complications.

PMID- 25753158
TI  - ERK kinase phosphorylates and destabilizes the tumor suppressor FBW7 in
      pancreatic cancer.
AB  - F-box and WD repeat domain-containing 7 (FBW7) is the substrate recognition
      component of the Skp1-Cul1-F-box (SCF) ubiquitin ligase complex and functions as
      a major tumor suppressor by targeting various oncoproteins for degradation.
      Genomic deletion or mutation of FBW7 has frequently been identified in many human
      cancers but not in pancreatic ductal adenocarcinoma. Thus it is important to know
      how the tumor suppressive function of FBW7 is impaired in pancreatic cancer. In
      this study, we first observed that low FBW7 expression correlated significantly
      with ERK activation in pancreatic cancer clinical samples, primarily due to KRAS
      mutations in pancreatic cancer. We further showed that ERK directly interacted
      with FBW7 and phosphorylated FBW7 at Thr205, which sequentially promoted FBW7
      ubiquitination and proteasomal degradation. Furthermore, the phospho-deficient
      T205A FBW7 mutant is resistant to ERK activation and could significantly suppress
      pancreatic cancer cell proliferation and tumorigenesis. These results
      collectively demonstrate how the oncogenic KRAS mutation inhibits the tumor
      suppressor FBW7, thus revealing an important function of KRAS mutations in
      promoting pancreatic cancer progression. 

PMID- 25753160
TI  - Giant oocytes in human in vitro fertilization treatments.
AB  - PURPOSE: Giant oocytes are potential sources of chromosomal abnormalities and
      should thus never be used in in vitro fertilization and embryo transfer (IVF-ET)
      procedures. The presence of giant oocytes may indicate the efficiency of the
      ovarian stimulation and can refer to the quality of sibling oocytes. METHODS: IVF
      cycles performed between January 2008 and November 2013 (n = 1521) were divided
      into two groups: Giant Oocyte Group (GO Group) contained cycles with at least one
      giant oocyte in the cohort of the retrieved oocytes (n = 37), Normal Group
      contained cycles with no giant oocytes (n = 1484). In the second part of the
      study, cycles from GO Group and Normal Group were matched according to patient
      age, number of retrieved oocytes and stimulation protocol, and thus 30 pairs were
      formed. Clinical and embryological data were analyzed. RESULTS: The incidence of
      giant oocytes was 0.3 %. The average patient age was lower (33.5 +/- 3.9 vs. 35.3
      +/- 4.9, p = 0.02); estradiol (E2) levels (1954 +/- 903 vs. 1488 +/- 909 pg/l, p
      < 0.01) and number of retrieved oocytes (12.7 +/- vs 8.1 +/- 5.1, p < 0.01) were
      significantly higher in the GO Group. There was no difference in clinical
      pregnancy rates (37.8 vs. 37.4 %, p = 1.00) between the two groups. No major
      differences in the embryo qualities were found. In the second part of the study,
      fertilization rate in the matched GO Group was lower (50.6 +/- 21.9 vs. 61.9 +/-
      22.4 %, p = 0.04). Clinical pregnancy rates (36.7 vs. 36.7 %, p = 1.00) did not
      differ between the matched cycles. CONCLUSIONS: Our data suggest that the
      stimulation protocol does not affect the incidence of giant oocytes. Giant
      oocytes present in cycles with higher number of retrieved oocytes in younger
      women. The presence of these gametes does not refer to the quality of sibling
      oocytes and embryos, or the outcome of the treatment.

PMID- 25753161
TI  - Papular acantholytic dyskeratosis occurring on both the vulvar and palmoplantar
      areas.

PMID- 25753162
TI  - Evaluation of fully biodegradable nasal packings in functional endoscopic sinus
      surgery - a multi-centre study.
AB  - THE AIM: This work was to compare an innovative solution, i.e. a fully
      biodegradable nasal packing Nasopore(r), with a traditional one, in the aftercare
      of patients subjected to functional endoscopic sinus surgery. MATERIAL AND
      METHOD: Prospective, blinded study with sequential enrollment conducted at three
      study centres. One of the investigators evaluated during surgery the level of
      bleeding in each of the nasal cavities and at the end of surgery he applied the
      test packing, the biodegradable dressing Nasopore(r), to one randomly chosen
      nasal cavity, and a control packing to the other one. The other investigator
      removed during aftercare the control packing and conducted the follow-up. During
      the control visits (24-48 hours, 10 and 30 days post-op.) the subjects evaluated
      their headache, pain in the nose, pressure in the forehead as well as their nasal
      obstruction. RESULTS: A total of 39 women and 44 men at the age of 47 years on
      average (min. 19, max. 82) were qualified for the study. The largest differences
      between different types of nasal dressings were observed with regard to reduction
      of nasal obstruction in the fist 10 days after surgery (P<0.005). In relation to
      the pain in the area of the head and nose as well the pressure in the forehead on
      every visit, better outcomes were observed for the test dressing. Statistical
      difference (P<0.05) was observed on the fist follow-up visit for the headache and
      pressure in the forehead as well as on the fist and second visit for the pain in
      the nose. CONCLUSION: The fully biodegradable nasal dressing Nasopore(r) may
      constitute significant improvement and facilitation of aftercare in functional
      endoscopic sinus surgery while increasing the patients' satisfaction and lowering
      the postoperative discomfort.

PMID- 25753163
TI  - Role of extended histological examination in the assessment of local recurrence
      of the oral cancer.
AB  - INTRODUCTION: Oral cancer is the second most prevalent head and neck malignancy
      in Poland. The incidence of these types of cancer is constantly growing. A reason
      for a treatment failure of the oral cancer is local recurrence. AIM OF THE STUDY:
      To find out why the rate of recurrence of the oral cancer is so high despite
      radical surgical treatment combined with radiochemotherapy. MATERIALS AND
      METHODS: The study comprised a group of 160 oral cancer patients. 30 patients who
      showed local recurrence were given an extended histopathological examination in
      keeping to the guidelines of the Royal College of Pathologists. RESULTS: In 9
      patients, primary tumours were found to be histologically aggressive as indicated
      by the proliferation of the vessels, nerves and muscles. In next 9 cases, the
      cancer infiltrated both the vessels and nerves or the vessels and muscles, and in
      the 8 other cases, just one of those structures. The tumours which were found to
      penetrate the vessels, nerves and muscles were also characterised with peri- and
      intraneural infiltration. The aggressiveness of invasion measured by the extent
      of damage done to the muscles, vessels and nerves correlated with the depth of
      invasion from the mucous membrane, the occurrence of embolisms in blood vessels,
      and a high (score 4) risk assessment as proposed by Margaret Brandwein-Gensler.
      CONCLUSION: The progression of cancer depends strongly on histopathological
      features. The incidence of penetration of the vessels, nerves and muscles
      correlates with aggressiveness of the front of tumour and few other histological
      features.

PMID- 25753164
TI  - A study of clinical presentations and complications of foreign body in the
      bronchus - own experience.
AB  - OBJECTIVES: In this study, we studied varied clinical presentations and
      complications of a foreign body in the airway and complications of bronchoscopy,
      if carried out. METHODS: A prospective observational clinical study in a tertiary
      care centre from June 2010 to May 2012 included 46 paediatric patients aged less
      than 12 years, with suspected foreign body aspiration, all of whom underwent
      rigid bronchoscopy under general anaesthesia. All the patients were subjected to
      history taking, clinical examination, and investigations (pre- and post-op chest
      X-ray and CT virtual bronchoscopy, if required). RESULTS: The most common age of
      presentation was 1 to 3 years, within 48 hours from aspiration. A total of 87% of
      patients had a definite history of aspiration, with cough (69.5%), and unilateral
      decreased air entry (91.3%) being the most common symptom and clinical sign,
      respectively. Emphysema was the most frequent finding on chest X-ray (71.7%), and
      the sensitivity of CT virtual bronchoscopy was 80%. Majority of the foreign
      bodies were organic (84.7% - especially peanuts) and mostly found in the right
      bronchus (47.8%). Post-op complications were rare (pneumothorax, pneumonic
      patch), and were managed conservatively. None of the patients required a
      tracheostomy and there was zero mortality. CONCLUSIONS: A positive history is by
      itself an indication for bronchoscopy. Clinical signs and X-ray changes should
      guide the clinicians towards the possible location of the foreign body. CT
      virtual bronchoscopy can be carried out in suspected cases with no specific
      history or clinical signs. Bronchoscopy can be conducted with minimal
      complications when performed by co-ordination of an expert surgeon and an
      anaesthetist.

PMID- 25753165
TI  - Consenting Practice of ENT Trainees: To What Extent Is Trainee Involvement
      Disclosed?
AB  - AIM: To assess to what extent ENT trainees disclose their involvement in
      operations to their patients when obtaining consent. BACKGROUND: It is not clear
      how the trainees are conducting the consenting process, although it could lead to
      a medico-legal conflict. DESIGN AND PARTICIPANTS: A 6-question questionnaire was
      sent via email to 22 ENT trainees in Northern Deanery, and 14 ENT registrars in
      Yorkshire Deanery. MAIN OUTCOME MEASURES: Seniority of the participants.
      Disclosure of the main operating surgeon and trainee involvement in the
      consenting process. Influence of operation complexity in trainee involvement
      disclosure. RESULTS: The response rate was 69%. Of the respondents, 46%
      consistently informed patients about trainee involvement in operations. Only 28%
      felt the complexity of operations influenced their decision to disclose trainee
      involvement. Subgroup analysis showed there was no statistically significant
      difference between junior and senior trainees in trainee involvement disclosure.
      If the trainees informed patients about who the operator would be, it was more
      likely for them to also disclose their own involvement. Many trainees also felt
      that the 'no guarantee of a particular surgeon' clause in the National Health
      Service consent form implied possible trainee involvement even if they did not
      specify it verbally. CONCLUSION: The rate of trainee involvement disclosure is
      not related to the seniority of trainee or complexity of operations, but is
      related to operator disclosure. This may suggest trainee involvement disclosure
      is not dependent on the level of confidence of trainees but on the approach and
      attitude towards the consenting process.

PMID- 25753166
TI  - Smell impairment in chronic rhinosinusitis - evaluation of endoscopic sinus
      surgery results and review of literature concerning olfactory function
      predictors.
AB  - INTRODUCTION: Endoscopic sinus surgery (ESS) is the treatment of choice for
      patients with chronic rhinosinusitis (CRS) refractory to medical therapy. ESS
      successfully reduces most symptoms of CRS, but its effect on olfaction is always
      uncertain. AIM OF THE STUDY: The aim of this study was to assess the influence of
      sinus surgery on olfaction and to analyze the predictors of olfactory function
      before and after ESS in the context of a literature review. MATERIAL AND METHODS:
      The study group comprised of 153 patients with CRS refractory to medical
      treatment. The patients evaluated their olfactory function before ESS, 3-6 months
      after ESS (121 individuals) and 12 months after ESS (58 individuals). Statistical
      analysis concerned the postoperative olfactory improvement as well as the
      influence of various predictors on the impairment of smell before and after
      surgery. RESULTS AND CONCLUSIONS: Olfactory dysfunction was significantly reduced
      after ESS. The smell impairment before and after surgery depended on different
      predictors. Patients with severe preoperative olfactory dysfunction and extensive
      pathological changes in the nose and sinuses, including nasal polyps, reported
      most pronounced improvement after ESS. However, severely hyposmic subjects with
      nasal polyposis, asthma or aspirin intolerance as well as older patients reported
      worse postoperative smell scores.

PMID- 25753167
TI  - Comparison of voice quality in patients with GERD-related larynx and
      layngopharynx disorders before and after therapy.
AB  - OBJECTIVES: The aim of this study was to compare voice quality in patients with
      GERD-related changes in the larynx and laryngopharynx before and after treatment.
      MATERIAL AND METHODS: 249 consecutive patients diagnosed with GERD-related
      changes in larynx and laryngopharynx were involved in this retrospective study
      (166 females, 83 males). Patients completed the questionnaire RSI. The GRBAS
      scale was used for subjective voice evaluation. Objective voice analysis was
      performed with the use of KAY Elemetrics Model CSL 4300 (CSL 4305, MDVP).
      RESULTS: In women, the mean RSI score (by Belafsky) was 12.69, in men 12.6. In
      both analyzed groups, the laryngeal symptoms related to GERD diminished after
      treatment. Perceptual assessment of voice (GRBAS) revealed G2R1B0A0S1 in women
      and G2R2B0A0S1 in men. In both the male and female group before treatment, the
      dominant sonogram was type III in Remacle's scale, IInd degree of hoarseness in
      Yanagihara's scale, phonation time was shortened, and MDVP parameters were
      abnormal. After treatment there was statistically significant improvement in the
      following parameters: G, R, B, and S in sonogram, degree of hoarseness, some of
      MDVP parameters (Fhi, RAP and PPQ in females, and F0 and Flo in males), and less
      irregularity in tomogram. CONCLUSIONS: In all patients no restoration of normal
      voice was noted after treatment despite disappearance of the gastrological
      symptoms.

PMID- 25753168
TI  - Saponins: Anti-diabetic principles from medicinal plants - A review.
AB  - Diabetes mellitus (DM) represents a global health problem. It is the most common
      of the endocrine disorders and is characterized by chronic hyperglycemia due to
      relative or absolute lack of insulin secretion or insulin actions. According to
      the World Health Organization projections, the diabetes population is likely to
      increase to 300 million or more by the year 2025. Current synthetic agents and
      insulin used effectively for the treatment of diabetes are scarce especially in
      rural areas, expensive and have prominent adverse effects. Complementary and
      alternative approaches to diabetes management such as isolation of phytochemicals
      with anti-hyperglycemic activities from medicinal plants is therefore imperative.
      Saponins are phytochemical with structural diversity and biological activities.
      This paper reviews saponins and various plants from which they were isolated as
      well as properties that make them ideal for antidiabetic remedy. 

PMID- 25753169
TI  - Testing a cycle of family violence model in conflict-affected, low-income
      countries: a qualitative study from Timor-Leste.
AB  - The present study examines key aspects of an emerging cycle of violence model as
      applied to conflict-affected countries. We focus specifically on the roles of
      intimate partner violence (IPV), consequent experiences of explosive anger
      amongst women, and associated patterns of harsh parenting. Between 2010 and 2011,
      we conducted a women-centred and culturally sensitive qualitative inquiry with 77
      mothers drawn consecutively from a data-base of all adults residing in two
      villages in Timor-Leste. We over-sampled women who in the preceding whole of
      household survey met criteria for Intermittent Explosive Disorder (IED). Our
      methodology included in-depth qualitative interviews followed by a focus group
      with a comprehensive array of service providers. We used the NVivo software
      package to manage and analyse data. Our findings provide support for a link
      between IPV and experiences of explosive anger amongst Timorese mothers.
      Furthermore, women commonly reported that experiences of explosive anger were
      accompanied by harsh parenting directed at their children. Women identified the
      role of patriarchy in legitimizing and perpetuating IPV. Our findings suggest
      that empowering women to address IPV and poverty may allow them to overcome or
      manage feelings of anger in a manner that will reduce risk of associated harsh
      parenting. A fuller examination of the cycle of violence model will need to take
      into account wider contributing factors at the macro-level (historical, conflict
      related, political), the meso-level (community-wide adherence to patriarchal
      norms affecting the rights and roles of women), and the micro-level (family
      interactions and gendered role expectations, individual psychological responses,
      and parenting). Longitudinal studies in post-conflict settings are needed to
      examine whether the sequence of male violence against women, mothers experience
      of explosive anger, and consequent harsh parenting contributes to risk of
      aggression and mental disorder in offspring, both in childhood and adulthood. 

PMID- 25753170
TI  - Impact of policy and built environment changes on obesity-related outcomes: a
      systematic review of naturally occurring experiments.
AB  - Policies and changes to the built environment are promising targets for obesity
      prevention efforts and can be evaluated as 'natural'- or 'quasi'-experiments.
      This systematic review examined the use of natural- or quasi-experiments to
      evaluate the efficacy of policy and built environment changes on obesity-related
      outcomes (body mass index, diet or physical activity). PubMed (Medline) was
      searched for studies published 2005-2013; 1,175 abstracts and 115 papers were
      reviewed. Of the 37 studies included, 18 studies evaluated impacts on
      nutrition/diet, 17 on physical activity and 3 on body mass index. Nutrition
      related studies found greater effects because of bans/restrictions on unhealthy
      foods, mandates offering healthier foods, and altering purchase/payment rules on
      foods purchased using low-income food vouchers compared with other interventions
      (menu labelling, new supermarkets). Physical activity-related studies generally
      found stronger impacts when the intervention involved improvements to active
      transportation infrastructure, longer follow-up time or measured process outcomes
      (e.g., cycling rather than total physical activity), compared with other studies.
      Only three studies directly assessed body mass index or weight, and only one
      (installing light-rail system) observed a significant effect. Studies varied
      widely in the strength of their design and studies with weaker designs were more
      likely to report associations in the positive direction.

PMID- 25753171
TI  - Developmental timing of perchlorate exposure alters threespine stickleback dermal
      bone.
AB  - Adequate levels of thyroid hormone are critical during development and
      metamorphosis, and for maintaining metabolic homeostasis. Perchlorate, a common
      contaminant of water sources, inhibits thyroid function in vertebrates. We
      utilized threespine stickleback (Gasterosteus aculeatus) to determine if timing
      of perchlorate exposure during development impacts adult dermal skeletal
      phenotypes. Fish were exposed to water contaminated with perchlorate (30mg/L or
      100mg/L) beginning at 0, 3, 7, 14, 21, 42, 154 or 305days post fertilization
      until sexual maturity at 1year of age. A reciprocal treatment moved stickleback
      from contaminated to clean water on the same schedule providing for different
      stages of initial exposure and different treatment durations. Perchlorate
      exposure caused concentration-dependent significant differences in growth for
      some bony traits. Continuous exposure initiated within the first 21days post
      fertilization had the greatest effects on skeletal traits. Exposure to
      perchlorate at this early stage can result in small traits or abnormal skeletal
      morphology of adult fish which could affect predator avoidance and survival. 

PMID- 25753172
TI  - Membranous nephropathy and cerebellar degeneration with anti-GAD antibodies in
      type 2 diabetes mellitus.
AB  - AIMS: To study the potential pathogenic significance of the coexistence of
      membranous nephropathy, cerebellar degeneration and anti-glutamic acid
      decarboxylase (GAD) autoantibodies in patients with diabetes. METHODS: We
      performed a direct immunocytochemistry on human kidney slides, electron
      microscopy on human kidney biopsy, direct immunofluorescence on human kidney
      biopsy. Baboon and rat kidney cell lines were fractionated and subjected to
      western blotting with antibodies to GAD. RESULTS: In this patient we demonstrate
      the presence of autoantibodies to GAD, which is highly enriched in podocytes
      plasma membrane and tubular cells of the kidney as well as sub-endothelial IgG
      and complement C3 deposits in the glomerular basement membrane (GBM).
      CONCLUSIONS: We hypothesize the existence in this patient of a common autoimmune
      pathogenic mechanism with GAD as the autoantigenic determinant, underlying
      cerebellar degeneration and membranous nephropathy.

PMID- 25753173
TI  - Kidney function and cerebral small vessel disease in the general population.
AB  - BACKGROUND: Anatomic and hemodynamic similarities between renal and cerebral
      vessels suggest a tight link between kidney disease and brain disease. Although
      several distinct markers are used to identify subclinical kidney and brain
      disease, a comprehensive assessment of how these markers link damage at both end
      organs is lacking. AIM: To investigate whether measures of kidney function were
      associated with cerebral small vessel disease on MRI. METHODS: In 2526
      participants of the population-based Rotterdam Study, we measured urinary albumin
      to-creatinine ratio, and estimated glomerular filtration rate based on serum
      creatinine and cystatin C. All participants underwent brain magnetic resonance
      imaging. We assessed presence of cerebral small vessel disease by calculating
      white matter lesion volumes and rating the presence of lacunes and cerebral
      microbleeds. We used multivariable linear and logistic regression to investigate
      the association between kidney function and cerebral small vessel disease.
      RESULTS: Worse kidney function was consistently associated with a larger white
      matter lesion volume (mean difference per standard deviation increase in albumin
      to-creatinine ratio: 0.09, 95% confidence interval 0.05; 0.12; per standard
      deviation decrease in creatinine-based estimated glomerular filtration rate: 
      0.04, 95% confidence interval -0.08;-0.01, and per standard deviation decrease in
      cystatin C-based estimated glomerular filtration rate: -0.09, 95% confidence
      interval -0.13;-0.05). Persons with higher albumin-to-creatinine ratio or lower
      cystatin C-based estimated glomerular filtration rate levels had a higher
      prevalence of lacunes (odds ratio per standard deviation increase in albumin-to
      creatinine ratio: 1.24, 95% confidence interval 1.07; 1.43). Only participants in
      the highest quartile of albumin-to-creatinine ratio had a higher frequency of
      microbleeds compared to the lowest quartile. CONCLUSIONS: Worse kidney function
      is associated with cerebral small vessel disease. Of all measures of kidney
      function, in particular albumin-to-creatinine ratio is related to cerebral small
      vessel disease.

PMID- 25753174
TI  - Update on vaccination guidelines for older adults.
AB  - Vaccination is a vital component of routine preventative health. Older adults can
      potentially benefit most from vaccines because they have greater susceptibility
      to disease and associated complications. The number of infections covered and the
      types of vaccines available has grown significantly in recent years. Although
      this represents tremendous progress, it can also result in confusion and missed
      opportunities to provided recommended vaccinations. This review summarizes the
      current guidelines for vaccination of older adults and highlights the latest
      innovations. 

PMID- 25753175
TI  - Living kidney donors' experiences while undergoing evaluation for donation: a
      qualitative study.
AB  - AIM AND OBJECTIVE: To explore living kidney donors' experiences during the donor
      evaluation process. BACKGROUND: Due to a shortage of organs for kidney
      transplantation from deceased donors, the living kidney donation rate has
      increased. The time period until transplantation is often shorter when using
      living donors compared to deceased donors. Although technological developments in
      immunology have made it possible to perform successful kidney transplants between
      donors and recipients, a large disparity still exists between the number of
      patients needing a kidney transplant and the supply of kidneys from living
      donors. This need has promoted donation from living kidney donors. The evaluation
      phase prior to donation is a crucial period in the recruitment of living kidney
      donors, as it ensures that donors are physically and mentally suitable for
      donation. DESIGN: A qualitative study taking a phenomenological-hermeneutic
      approach. METHODS: Data were generated using participant observation during the
      evaluation period and semi-structured interviews after conclusion of the
      evaluation. In total, 18 potential donors were included. Data were interpreted
      and discussed in accordance with Ricoeur's theory of interpretation: naive
      reading, structural analysis, critical interpretation and discussion. RESULTS:
      Feelings of hope concerning acceptance as a donor and concerns for the
      recipient's illness and everyday life were evident during evaluation. Donors'
      experiences largely depended on the quality of their communication and
      interaction with the healthcare professionals. In some cases, donors were
      supported and cared for, while in other cases, frustrations and vulnerability
      were evident and emotional support and attention to donors' needs were not
      present. CONCLUSION: The evaluation period for living kidney donation involves
      hope, vulnerability and concern. Interaction, communication and support from
      healthcare professionals to help donors manage this crucial phase are essential.
      Accordingly, the identification of donors' specific care and support needs,
      including physical, mental and ethical factors, is key to a positive experience.
      RELEVANCE TO CLINICAL PRACTICE: The attention, commitment and engagement of
      healthcare professionals are essential elements in the identification of donors'
      individual needs.

PMID- 25753176
TI  - Directional Recording of Subthalamic Spectral Power Densities in Parkinson's
      Disease and the Effect of Steering Deep Brain Stimulation.
AB  - BACKGROUND: A new 32-contacts deep brain stimulation (DBS) lead, capable of
      directionally steering stimulation, was tested intraoperatively. OBJECTIVE: The
      aim of this pilot study was to perform recordings from the multidirectional
      contacts and to investigate the effect of directional current steering on the
      local field potentials (LFPs). METHODS: In eight patients with Parkinson's
      disease, after standard microelectrode recording and clinical testing, the new
      lead was temporarily implanted. The 32-channel LFP recordings were measured
      simultaneously at different depths and directions before and after directional
      stimulation. RESULTS: The spatial distribution of LFPs power spectral densities
      across the contact array at baseline marked the borders of the subthalamic
      nucleus (STN) with a significant increase in beta power and with a mean accuracy
      of approximately 0.6 mm in four patients.The power in the 18.5-30 Hz frequency
      band varied across different directions in all patients. In the three cases that
      showed improvement of rigidity, this was higher when current was steered toward
      the direction with the highest LFP power in the beta band. Subthalamic LFPs in
      six patients showed a differential frequency-dependent suppression/enhancement of
      the oscillatory activity in the 10-45 Hz frequency band after four different
      'steering' modes as compared to ring mode, suggesting a higher specificity.
      CONCLUSIONS: Through a new 32-contact DBS lead it is possible to record
      simultaneous subthalamic LFPs at different depths and directions, providing
      confirmation of adequate lead placement and multidirectional spatial-temporal
      information potentially related to pathological subthalamic electrical activity
      and to the effect of stimulation. Although further research is needed, this may
      improve the efficiency of steering stimulation.

PMID- 25753177
TI  - The Right Angular Gyrus Combines Perceptual and Response-related Expectancies in
      Visual Search: TMS-EEG Evidence.
AB  - BACKGROUND: Visual search performance is sensitive to changes in the environment.
      Attention is sensitive to trial history, in terms of both perception and
      response. Although the bases of these sensorimotor interactions remain unclear,
      both behaviorally and neurally, converging evidence from a variety of methods
      indicates that the right angular gyrus (rANG) may be important.
      OBJECTIVE/HYPOTHESIS: The present study tests whether the rANG plays a causal
      role in generating these inter-trial effects. METHODS: Participants performed a
      compound task for feature singleton targets. We applied rTMS over the rANG (or a
      control site, or no TMS) during the inter-trial interval and measured effects
      both on behavior and on neural activity using psychophysics and event-related
      potential (ERP) recording. RESULTS: rANG TMS during the inter-trial interval
      improved performance to the upcoming stimuli only when the target-defining
      dimension and the response-defining feature both repeated across successive
      trials. rANG TMS also increased the amplitude of the visual N1 component evoked
      by the upcoming stimuli. These effects did not occur after control TMS.
      CONCLUSION: rANG plays a causal role in the formation of combined expectancies
      binding together stimulus- and response-characteristics of the previous trial to
      optimize visual search performance. This supports a visuomotor theory of parietal
      cortex and the dimension weighting account of attention. We suggest current
      models of inter-trial effects in visual search need to be expanded to include an
      interactive component representing both perceptual and motoric inter-trial
      expectancies, affecting the early analysis of stimulus features in the upcoming
      trial.

PMID- 25753178
TI  - Soluble suppression of tumorigenicity 2 (sST2), but not galactin-3, adds to
      prognostication in patients with systemic AL amyloidosis independent of NT-proBNP
      and troponin T.
AB  - The use of soluble cardiac biomarkers such as N-terminal pro-brain natriuretic
      peptide (NT-proBNP) and troponin has revolutionized prognostication for patients
      with AL amyloidosis. Soluble ST2 (sST2) and galectin-3 have also been reported to
      have prognostic value in other cardiac patient populations. We identified 502
      patients with AL amyloidosis, who provided a research sample and consent to
      review their medical records between 1/1/2006-12/31/2010 within 90 days of their
      diagnosis. Samples were assayed for sST2 and galectin-3. Within this AL
      amyloidosis population, overall survival (OS) was 25.5 months (95% CI 18, 35.7
      months). Receiver operating curve analyses were done to detect the best cut
      points for sST2 and galectin-3 to predict both 1- and 5-year OS. The respective
      cut points for sST2 were 30 and 29.7 ng/mL, while the median sST2 for the entire
      population was 31 ng/mL (IQR 19.8, 53.6). The respective cut points for galectin
      3 were 11 and 10.4 ng/mL while the median for the entire population was 16.6
      ng/mL (IQR 11.5, 24.0). Although on univariate analysis, both sST2 and galectin-3
      were prognostic, upon multivariate analysis, only sST2 was independent of
      troponin, NT-proBNP, serum immunoglobulin free light chain, and blood pressure.
      Not only did sST2 add to previously reported prognostication systems, but a novel
      prognostication 5-point system including sST2 was possible. The addition of sST2 
      but not galectin-3 - to existing prognostication systems for patients with AL
      amyloidosis strengthens the ability to predict for death.

PMID- 25753179
TI  - The promise of enhancer-associated long noncoding RNAs in cardiac regeneration.
AB  - Heart failure is a worldwide epidemic and represents a major cause of morbidity
      and mortality. Current clinical therapies for heart disease prolong survival by
      protecting the viable muscle, but they are unable to replenish lost
      cardiomyocytes to restore function. Over the last decade, the notion of promoting
      cardiac regeneration has engendered considerable research interest. New
      strategies envisage the transfer of stem cells into the damaged myocardium, the
      mobilization of cardiac precursor cells, the promotion of cardiomyocyte
      proliferation in situ and direct reprogramming of non-cardiac cells into
      electromechanically coupled cardiomyocytes. The molecular and cellular mechanisms
      underpinning these different regenerative avenues are under the control of
      integrated transcriptional programs, which are ultimately dependent on epigenomic
      reprogramming and reorganization of the genome nuclear architecture. Today, it is
      becoming evident that regulatory noncoding RNAs play fundamental roles in all
      these aspects of gene regulatory network activity. In particular, thousands of
      long noncoding RNAs are dynamically expressed across the entire genome during
      lineage-specific commitment, specialization, and differentiation, as well as
      during the response to environmental cues. Here, we review this emerging
      landscape, focusing particularly on a unique class of lncRNA emerging from
      enhancer sequences, the enhancer-associated lncRNAs, in the context of cardiac
      regeneration. We propose that characterizing and manipulating these enhancer
      associated transcripts could provide a novel approach to awaken the dormant
      regenerative potential of the adult mammalian heart. Ultimately, this could lead
      to targeted noncoding RNA-based enhancer therapies to improve effectiveness of
      current regenerative strategies and provide new avenues for repair. 

PMID- 25753180
TI  - Circulating endothelial cells in coronary artery disease and acute coronary
      syndrome.
AB  - Circulating endothelial cells (CECs) have been put forward as a promising
      biomarker for diagnosis and prognosis of coronary artery disease and acute
      coronary syndromes. This review entails current insights into the physiology and
      pathobiology of CECs, including their relationship with circulating endothelial
      progenitor cells and endothelial microparticles. Additionally, we present a
      comprehensive overview of the diagnostic and prognostic value of CEC
      quantification, as well as possibilities for improvement, for example, by
      inclusion of CEC morphology, transcriptomics, and proteomics. The current stand
      of knowledge calls out for improved counting methods and consensus on a validated
      cell definition. Finally, our review accentuates the importance of large, well
      designed, population-based prospective studies that will have to show the
      clinical value of CEC as a cardiovascular biomarker. 

PMID- 25753181
TI  - Good, Bad or Absent: Discourses of Parents with Disabilities in Australian News
      Media.
AB  - BACKGROUND: News media frames public perceptions. As such, news media becomes a
      useful source of analysis to understand the presence (or otherwise) of people
      with disabilities, particularly intellectual disabilities, within parenting
      discourses in Australia. METHOD: Using Critical Discourse Analysis, this article
      examines major Australian newspapers over the period from January 2004 to
      December 2008, critiquing the construction of parenting and disability. A small
      number of articles are examined in close depth for tone, polarity syntactic and
      paradigmatic choice, deconstructing the underlying discourses that shape the
      article and thereby popular perceptions of parenting and disability. DISCUSSION:
      Discourses of care and child protection are emphasized in news articles about
      parenting, creating perceptions that negate the role of people with disabilities
      as parents. Such perceptions result in a systematic symbolic castration of people
      with intellectual disabilities from the role of parent in Australian society.
      CONCLUSION: By providing a framework for understanding the public perceptions of
      parents with disabilities (particularly intellectual disabilities), this paper
      demonstrates that changes are necessary in Australian media reporting on parents
      with disabilities to bring such reporting more closely in line with the United
      Nations Convention on the Rights of Persons with Disabilities, 2006.

PMID- 25753182
TI  - Acceptability and Feasibility of a Meaning-Based Intervention for Patients With
      Advanced Cancer and Their Spouses: A Pilot Study.
AB  - BACKGROUND: Constructing meaning in cancer leads to improved psychosocial
      outcomes for patients and survivors. AIM: We tested the feasibility and
      preliminary efficacy of a meaning-based intervention for couples. DESIGN: The
      single-arm pilot study tested a 4-session, tailored, activities-based couple's
      intervention. SETTING/PARTICIPANTS: Twelve adults with incurable cancer and their
      partners participated either in a university office or at the couple's home.
      RESULTS: The study showed good feasibility. One of the two patients depressed at
      baseline was no longer depressed at postintervention. Patients' threat appraisals
      decreased and transcendence increased. In partners, depression, anxiety, and
      challenge appraisal decreased; threat and secondary appraisals and peace with
      illness increased. CONCLUSIONS: Our findings suggest feasibility and efficacy,
      and further research and continued evaluation of this intervention are warranted.

PMID- 25753183
TI  - A Pilot Curriculum to Integrate Standardized Patient Simulation into Clinical
      Pastoral Education.
AB  - INTRODUCTION: We describe a novel means of experiential learning for clinical
      pastoral care residents using standardized patient (SP) simulations. METHODS: A
      prospective cohort study involving 7 clinical pastoral care residents was
      performed. All residents underwent 2 verbatim SP sessions and 2 simulation
      sessions. After all sessions, residents completed a self-evaluation. Faculty
      completed an evaluation and then provided a debriefing session to all residents.
      RESULTS: Performance ratings were globally higher on simulated scenarios when
      compared to the verbatim sessions. CONCLUSIONS: More research in the field of
      pastoral care is needed to validate the learned professional skills that enhance
      a comprehensive training program through the use of medical simulation, verbatim
      reports, and clinical pastoral education (CPE) competencies. Medical simulation
      provides a promising teaching methodology for the training of CPE residents.

PMID- 25753184
TI  - Race, Any Cancer, Income, or Cognitive Function: What Inf luences Hospice or
      Aggressive Services Use at the End of Life Among Community-Dwelling Medicare
      Beneficiaries?

PMID- 25753185
TI  - Activation of G-protein coupled estrogen receptor inhibits the proliferation of
      cervical cancer cells via sustained activation of ERK1/2.
AB  - Cervical cancer is one of the most common gynaecological women cancer and
      suggested to be modulated by estrogenic signals. G protein-coupled receptor
      (GPER), a seven-transmembrane G protein-coupled receptor, has been reported to
      regulate the cell proliferation of various cancers. But there is no study
      investigating the effects of GPER on the progression of cervical cancer. In the
      present study, we revealed for the first time that GPER was also highly expressed
      in various human cervical cancer cells. Activation of GPER via its specific
      agonist G-1 induced G2/M cell cycle arrest and down regulation of cyclin B via a
      time dependent manner. Furthermore, G-1 treatment induced sustained activation of
      extracellular-signal-regulated kinases (ERK)1/2 via epidermal growth factor
      receptor (EGFR) signals. Both inhibitors of ERK1/2 and EGFR significantly
      abolished G-1-induced suppression of cell proliferation and down regulation of
      cyclin B. Generally, our study revealed that GPER is highly expressed in human
      cervical cancer cells and its activation inhibits cell proliferation via
      EGFR/ERK1/2 signals. It suggested that G-1 can be considered as a potential new
      pharmacological tool to reduce the growth of cervical cancer.

PMID- 25753186
TI  - Multi-chronic musculoskeletal pain is a useful clinical index to predict the risk
      of falls in older adults with normal motor function.
AB  - BACKGROUND: The number of chronic musculoskeletal pain sites (nCMSP) is
      reportedly associated with risk of falls. Older participants in community-based
      research show a wide range of physical functions, but few studies have focused on
      the risk of falls in older adults with normal motor function (NMF). Clarification
      of the effects of pain on dual-tasking performance is also important, given the
      strong link between falls and dual-tasking. AIMS: The objectives were to
      investigate the associations between: (1) nCMSP and falls; and (2) nCMSP and dual
      task performance in older adults with NMF. METHODS: A total of 112 older adults
      with NMF (44 men, 68 women; 73.4 +/- 4.6 years) were classified as fallers (n =
      22) or non-fallers (n = 90) according to their fall history. Musculoskeletal pain
      in the lower body was assessed using questions ascertaining pain in
      musculoskeletal sites (back, hip, knee, foot, or toe). Participants were assigned
      to three pain groups according to nCMSP. Basic physical performances and gait
      performances (normal gait, fast gait, or dual-task gait) were measured. RESULTS:
      The nCMSP represented a significant risk factor for falls according to logistic
      regression modeling after adjusting for the five chair stand test and fear of
      falls. The nCMSP was not associated with any gait variables. DISCUSSION:
      Potential fall risk may be increased by nCMSP, even in older adults with NMF.
      Pain-related reduction in attention resources may not represent a risk factor for
      falls among older adults with NMF. CONCLUSIONS: The nCMSP represents a potential
      risk factor for falls in older adults with NMF.

PMID- 25753187
TI  - Should external short courses be a compulsory part of ACEM specialty training?
      Yes.
AB  - Implementation of a series of mandatory short courses for ACEM trainees will
      necessitate clear pathways to accreditation, rigourous application of standards
      and demonstration by course providers of high-quality teaching of up-to-date
      practices. Trainees and their patients stand to reap wide-ranging benefits from
      these courses, which might also facilitate the transition to competency- (rather
      than time-) based training through the College. Completion by all trainees of
      compulsory courses will provide the community with clarity about the standards to
      which emergency physicians are trained and might result in improvements in
      patient outcomes - the very reason for our trainees' hard work and dedication.

PMID- 25753189
TI  - Survivorship - searching for new directions.

PMID- 25753188
TI  - Incidence of brain metastases in HER2+ gastric or gastroesophageal junction
      adenocarcinoma.

PMID- 25753190
TI  - High-level quinolone resistance is associated with the overexpression of smeVWX
      in Stenotrophomonas maltophilia clinical isolates.
AB  - Stenotrophomonas maltophilia is the only known bacterium in which quinolone
      resistant isolates do not present mutations in the genes encoding bacterial
      topoisomerases. The expression of the intrinsic quinolone resistance elements
      smeDEF, smeVWX and Smqnr was analysed in 31 clinical S. maltophilia isolates
      presenting a minimum inhibitory concentration (MIC) range to ciprofloxacin
      between 0.5 and > 32 MUg/mL; 11 (35.5%) overexpressed smeDEF, 2 (6.5%) presenting
      the highest quinolone MICs overexpressed smeVWX and 1 (3.2%) overexpressed Smqnr.
      Both strains overexpressing smeVWX presented changes at the Gly266 position of
      SmeRv, the repressor of smeVWX. Changes at the same position were previously
      observed in in vitro selected S. maltophilia quinolone-resistant mutants,
      indicating this amino acid is highly relevant for the activity of SmeRv in
      repressing smeVWX expression. For the first time SmeVWX overexpression is
      associated with quinolone resistance of S. maltophilia clinical isolates.

PMID- 25753191
TI  - Skin and soft tissue infections in intercontinental travellers and the import of
      multi-resistant Staphylococcus aureus to Europe.
AB  - Staphylococcus aureus is emerging globally. Treatment of infections is
      complicated by increasing antibiotic resistance. We collected clinical data and
      swabs of returnees with skin and soft tissue infections (SSTI) at 13 travel
      clinics in Europe (www.staphtrav.eu). Sixty-two percent (196/318) SSTI patients
      had S. aureus-positive lesions, of which almost two-thirds (122/196) were Panton
      Valentine leukocidin (PVL) positive. PVL was associated with disease severity,
      including hospitalization for SSTI (OR 5.2, 95% CI 1.5-18.2). In returnees with
      SSTI, longer travel and more intense population contact were risk factors for
      nasal colonization with PVL-positive S. aureus. Imported S. aureus frequently
      proved resistant to trimethoprim-sulfamethoxazole (21%), erythromycin (21%),
      tetracycline (20%), ciprofloxacin (13%), methicillin (12%) and clindamycin (8%).
      Place of exposure was significantly (p < 0.05) associated with predominant
      resistance phenotypes and spa genotypes: Latin America (methicillin;
      t008/CC24/304), Africa (tetracycline, trimethoprim-sulfamethoxazole; t084/CC84,
      t314/singleton, t355/CC355), South Asia (trimethoprim-sulfamethoxazole,
      ciprofloxacin; t021/CC21/318), South-East Asia (clindamycin; t159/CC272). USA300
      like isolates accounted for 30% of all methicillin-resistant S. aureus imported
      to Europe and were predominantly (71%) acquired in Latin America. Multi
      resistance to non-beta-lactams were present in 24% of imports and associated with
      travel to South Asia (ORcrude 5.3, 95% CI 2.4-11.8), even after adjusting for
      confounding by genotype (ORadjusted 3.8, 95% 1.5-9.5). Choosing randomly from
      compounds recommended for the empiric treatment of severe S. aureus SSTI, 15% of
      cases would have received ineffective antimicrobial therapy. These findings call
      for the development of regionally stratified guidance on the antibiotic
      management of severe imported S. aureus disease and put the infected and
      colonized traveller at the centre of interventions against the global spread of
      multi-resistant S. aureus.

PMID- 25753193
TI  - Health-seeking behaviour and community perceptions of childhood undernutrition
      and a community management of acute malnutrition (CMAM) programme in rural Bihar,
      India: a qualitative study.
AB  - OBJECTIVE: Since 2009, Medecins Sans Frontieres has implemented a community
      management of acute malnutrition (CMAM) programme in rural Biraul block, Bihar
      State, India that has admitted over 10 000 severely malnourished children but has
      struggled with poor coverage and default rates. With the aim of improving
      programme outcomes we undertook a qualitative study to understand community
      perceptions of childhood undernutrition, the CMAM programme and how these
      affected health-seeking behaviour. DESIGN: Semi-structured and narrative
      interviews were undertaken with families of severely malnourished children, non
      undernourished children and traditional and allopathic health-care workers.
      Analysis of transcripts was by qualitative content analysis. SETTING: Biraul,
      Bihar State, India, 2010. SUBJECTS: One hundred and fifty people were interviewed
      in individual or group discussions during fifty-eight interviews. RESULTS:
      Undernutrition was not viewed as a disease; instead, local disease concepts were
      identified that described the clinical spectrum of undernutrition. These concepts
      informed perception, so caregivers were unlikely to consult health workers if
      children were 'only skinny'. Hindu and Muslim priests and other traditional
      health practitioners were more regularly consulted and perceived as easier to
      access than allopathic health facilities. Senior family members and village
      elders had significant influence on the health-seeking behaviour of parents of
      severely malnourished children. CONCLUSIONS: The results reaffirm how health
      education and CMAM programmes should encompass local disease concepts, beliefs
      and motivations to improve awareness that undernutrition is a disease and one
      that can be treated. CMAM is well accepted by the community; however, programmes
      must do better to engage communities, including traditional healers, to enable
      development of a holistic approach within existing social structures.

PMID- 25753192
TI  - A switch from parallel to antiparallel strand orientation in a coiled-coil X-ray
      structure via two core hydrophobic mutations.
AB  - The coiled-coil is one of the most ubiquitous and well studied protein structural
      motifs. Significant effort has been devoted to dissecting subtle variations of
      the typical heptad repeat sequence pattern that can designate larger topological
      features such as relative alpha-helical orientation and oligomer size. Here we
      report the X-ray structure of a model coiled-coil peptide, HA2-Del-L2seM, which
      forms an unanticipated core antiparallel dimer with potential sites for discrete
      higher-order multimerization (trimer or tetramer). In the X-ray structure, a
      third, partially-ordered alpha-helix is weakly associated with the antiparallel
      dimer and analytical ultracentrifugation experiments indicate the peptide forms a
      well-defined tetramer in solution. The HA2-Del-L2seM sequence is closely related
      to a parent model peptide, HA2-Del, which we previously reported adopts a
      parallel trimer; HA2-Del-L2seM differs by only hydrophobic leucine to
      selenomethione mutations and thus this subtle difference is sufficient to switch
      both relative alpha-helical topology and number of alpha-helices participating in
      the coiled-coil. Comparison of the X-ray structures of HA2-Del-L2seM (reported
      here) with the HA2-Del parent (reported previously) reveals novel interactions
      involving the selenomethionine residues that promote antiparallel coiled-coil
      configuration and preclude parallel trimer formation. These novel atomic insights
      are instructive for understanding subtle features that can affect coiled-coil
      topology and provide additional information for design of antiparallel coiled
      coils.

PMID- 25753194
TI  - Maternalism: a healthy alliance for recovery and transition in eating disorder
      services.
AB  - ACCESSIBLE SUMMARY: The therapeutic relationship is pivotal to mental health
      nursing, but very little is known about how it is experienced in adult eating
      disorder services. This paper reports on a research project that sought to
      discover how the therapeutic relationship is experienced between care workers and
      women with anorexia nervosa in an adult eating disorder service. Both care
      workers and women spoke of a relationship that had similarities to the mother
      daughter relationship, that it felt therapeutic and that it was in keeping with a
      professional and compassionate nursing approach. These findings provide new
      insight. Maternalism is seen as a positive, nurturing and transient relationship
      that ensures the safety of the person and promotes recovery and transition to
      eventual independence. ABSTRACT: This paper reports on a UK interpretative
      phenomenological research study that aimed to explore the lived experience of the
      relationship between women with anorexia and their care workers in the context of
      a specialist eating disorder (ED) unit. Here, the concept of maternalism as a
      phenomenon occurring within the therapeutic relationship in specialist ED units
      is discussed. Consideration is given to the parallel roles of the health care
      worker whose duty it is to protect, preserve life and to promote health and that
      of a mother/guardian. Although seemingly simplistic, the comforting, soothing and
      nurturing techniques that are used by the workers to diffuse distress and help
      the person feel cared for have many similarities to 'mothering'. Hence, a
      maternalistic approach that provides a sense of security and nurturing can be a
      compassionate way to facilitate hope and a route out of their anorexia into
      recovery, in the same way that good parenting can facilitate maturation and
      independence.

PMID- 25753195
TI  - Modified vibrating-mesh nozzles for advanced spray-drying applications.
AB  - This work describes uniform polymer coatings allowing for an adjustment of the
      orifice dimension of vibrating-mesh nozzles and therefore, size of emerging
      formulation droplets and dried particles, which is of general interest for
      diverse spray-drying applications. Chemical vapor deposition of poly(p-xylylene)
      (PPXN) on aperture templates of the B-90 spray-dryer (orifice diameters: ~4.0MUm)
      caused a reduction of the opening cross-sections of ~50%. Thus, a more efficient
      formulation atomization was observed (finer droplets). Likewise, application of
      PPXN-coated, rather than plain nozzles, resulted in significantly smaller
      (particle diameter: 1.3 vs. 3.6MUm) and narrower distributed (span: ~1.4 vs.
      ~1.8) sildenafil-loaded poly(lactide-co-glycolide) microparticles. Prediction of
      the size of spray-dried microparticles using the size results of atomized
      droplets ("residual core method") was shown to be in agreement with the observed
      values. Formulations prepared with plain and PPXN-coated nozzles exhibited a
      sustained sildenafil release profile with mean dissolution times of ~1.5 and
      ~4.0h, respectively. Regardless of the starting aperture template, any desired
      orifice dimension and therefore, dried particle size could be achieved by
      generating adequate polymer deposits. 

PMID- 25753196
TI  - Hemolytic activity and solubilizing capacity of raffinose and melezitose fatty
      acid monoesters prepared by enzymatic synthesis.
AB  - The hemolytic activity and solubilizing capacity of two families of non-reducing
      trisaccharide fatty acid monoesters have been studied to assess their usefulness
      as surfactants for pharmaceutical applications. The carbohydrate-based
      surfactants investigated included homologous series of raffinose and melezitose
      monoesters bearing C10 to C18 acyl chains prepared by lipase-catalyzed synthesis
      in organic media. The hemolytic activity was determined in vitro using a static
      method based on the addition of the surfactants to an erythrocyte suspension and
      subsequent spectrophotometric determination of the released hemoglobin. The
      effect of the carbohydrate head group, the acyl chain length and the
      regioisomeric purity was investigated. In all cases, the carbohydrate monoester
      surfactants decreased their hemolytic activity (with respect to their critical
      micelle concentration) when increasing the length of the acyl chain. A very
      similar behaviour was observed either the carbohydrate head-group (raffinose and
      melezitose) or regardless of the regioisomeric purity. Interestingly, decanoyl
      (C10) and lauroyl (C12) monoesters were just marginally hemolytic at their
      critical micelle concentrations while the longer palmitoyl (C16) and (C18)
      stearoyl monoesters become hemolytic at concentrations much higher than their
      respective cmc. The palmitoyl and stearoyl monoesters also displayed higher
      solubilization capacity than the shorter acyl chain monoesters in a
      solubilization assay of a hydrophobic dye as a model drug mimic. These results
      suggest that raffinose and melezitose monoesters with long-chain fatty acids (C16
      to C18) are promising surfactants for pharmaceutical applications and could be an
      alternative to the use of current commercial nonionic polyoxyethylene-based
      surfactants in parenteral formulations. 

PMID- 25753198
TI  - Physicochemical properties of pH-sensitive hydrogels based on hydroxyethyl
      cellulose-hyaluronic acid and for applications as transdermal delivery systems
      for skin lesions.
AB  - We investigated the physicochemical properties of pH-sensitive hydroxyethyl
      cellulose (HEC)/hyaluronic acid (HA) complex hydrogels containing
      isoliquiritigenin (ILTG), and discussed potential applications as transdermal
      delivery systems for the treatment of skin lesions caused by pH imbalance. HA has
      skin compatibility and pH functional groups and HEC serves as scaffold to build
      hydrogels with varied HCE:HA mass ratio. Hydrogels were synthesized via chemical
      cross-linking, and three-dimensional network structures were characterized via
      scanning electron microscopy (SEM). The swelling properties and polymer ratios of
      the hydrogels were investigated at pH values in the range 1-13. HECHA13 (i.e., an
      HEC:HA mass ratio of 1:3) was found to have optimal rheological and adhesive
      properties, and was used to investigate the drug release efficiency as a function
      of pH; the efficiency was greater than 70% at pH 7. Antimicrobial activity assays
      against Propionibacterium acnes were conducted to take advantage of the pH
      sensitive properties of HECHA13. At pH 7, we found that HECHA13, which contained
      ILTG, inhibited the growth of P. acnes. Furthermore, HECHA13 was found to exhibit
      excellent permeability into the skin, which penetrated mostly via the hair
      follicle. These results indicate that this pH-sensitive hydrogel is effective as
      a transdermal delivery system for antimicrobial therapeutics, with potential
      applications in the treatment of acne. 

PMID- 25753197
TI  - Release kinetics of paclitaxel and cisplatin from two and three layered gold
      nanoparticles.
AB  - Gold nanoparticles functionalized with biologically compatible layers may achieve
      stable drug release while avoiding adverse effects in cancer treatment. We study
      cisplatin and paclitaxel release from gold cores functionalized with
      hexadecanethiol (TL) and phosphatidylcholine (PC) to form two-layer
      nanoparticles, or TL, PC, and high density lipoprotein (HDL) to form three-layer
      nanoparticles. Drug release was monitored for 14 days to assess long term effects
      of the core surface modifications on release kinetics. Release profiles were
      fitted to previously developed kinetic models to differentiate possible release
      mechanisms. The hydrophilic drug (cisplatin) showed an initial (5-h) burst,
      followed by a steady release over 14 days. The hydrophobic drug (paclitaxel)
      showed a steady release over the same time period. Two layer nanoparticles
      released 64.0+/-2.5% of cisplatin and 22.3+/-1.5% of paclitaxel, while three
      layer nanoparticles released the entire encapsulated drug. The Korsmeyer-Peppas
      model best described each release scenario, while the simplified Higuchi model
      also adequately described paclitaxel release from the two layer formulation. We
      conclude that functionalization of gold nanoparticles with a combination of TL
      and PC may help to modulate both hydrophilic and hydrophobic drug release
      kinetics, while the addition of HDL may enhance long term release of hydrophobic
      drug.

PMID- 25753199
TI  - The evolution of fetal presentation during pregnancy: a retrospective,
      descriptive cross-sectional study.
AB  - We investigated changes in the frequencies of four primary types of singleton
      fetal lie/presentation for each gestational week from 18 to 39 weeks in a
      retrospective, cross-sectional study which analyzed ultrasound examination
      records of fetal positions, in the outpatient prenatal diagnosis clinics in two
      cities in Poland. We calculated the prevalence and 95% confidence intervals for
      each type of lie/presentation. We then identified the gestational age after which
      no statistically significant changes in terms of prevalence were observed, by
      comparing the results at each week with the prevalence of cephalic presentation
      at 39(+0) weeks, used as reference. A total of 18 019 ultrasound examinations
      were used. From 22 to 36 weeks of gestation, the prevalence of cephalic
      presentation increased from 47% (45-50%) to 94% (91-96%), before and after which
      times plateaus were noted. Spontaneous change from breech to cephalic is unlikely
      to occur after 36 weeks of gestation.

PMID- 25753200
TI  - A novel biphenyl urea derivate inhibits the invasion of breast cancer through the
      modulation of CXCR4.
AB  - The increased migration and invasion of breast carcinoma cells are key events in
      the development of metastasis to the lymph nodes and distant organs. CXCR4, the
      receptor for stromal-derived factor-1, is reportedly involved in breast
      carcinogenesis and invasion. In this study, we investigated a novel biphenyl urea
      derivate, TPD7 for its ability to affect CXCR4 expression as well as function in
      breast cancer cells. We demonstrated that TPD7 inhibited the breast cancer
      proliferation and down-regulated the CXCR4 expression on breast cancer cells both
      over-expressing and low-expressing HER2, an oncogene known to induce the
      chemokine receptor. Treatments with pharmacological proteasome inhibitors partial
      suppressed TPD7-induced decrease in CXCR4 expression. Real-time PCR analysis
      revealed that down-regulation of CXCR4 by TPD7 also occurred at the translational
      level. Inhibition of CXCR4 expression by TPD7 further correlated with the
      suppression of SDF-1alpha-induced migration and invasion in breast tumour cells,
      knockdown of CXCR4 attenuated TPD7-inhibitory effects. In addition, TPD7
      treatment significantly suppressed matrix metalloproteinase (MMP)-2 and MMP-9
      expression, the downstream targets of CXCR4, perhaps via inactivation of the ERK
      signaling pathway. Overall, our results showed that TPD7 exerted its anti
      invasive effect through the down-regulation of CXCR4 expression and thus had the
      potential for the treatment of breast cancer. 

PMID- 25753201
TI  - Solution structure of the porcine sapovirus VPg core reveals a stable three
      helical bundle with a conserved surface patch.
AB  - Viral protein genome-linked (VPg) proteins play a critical role in the life cycle
      of vertebrate and plant positive-sense RNA viruses by acting as a protein primer
      for genome replication and as a protein cap for translation initiation. Here we
      report the solution structure of the porcine sapovirus VPg core (VPg(C))
      determined by multi-dimensional NMR spectroscopy. The structure of VPg(C) is
      composed of three alpha-helices stabilized by several conserved hydrophobic
      residues that form a helical bundle core similar to that of feline calicivirus
      VPg. The putative nucleotide acceptor Tyr956 within the first helix of the core
      is completely exposed to solvent accessible surface to facilitate
      nucleotidylation by viral RNA polymerase. Comparison of VPg structures suggests
      that the surface for nucleotidylation site is highly conserved among the
      Caliciviridae family, whereas the backbone core structures are different. These
      structural features suggest that caliciviruses share common mechanisms of VPg
      dependent viral replication and translation. 

PMID- 25753202
TI  - The role of microRNA-1274a in the tumorigenesis of gastric cancer: accelerating
      cancer cell proliferation and migration via directly targeting FOXO4.
AB  - MicroRNAs (miRNAs) are a series of 18-25 nucleotides length non-coding RNAs,
      which play critical roles in tumorigenesis. Previous study has shown that
      microRNA-1274a (miR-1274a) is upregulated in human gastric cancer. However, its
      role in gastric cancer progression remains poorly understood. Therefore, the
      current study was aimed to examine the effect of miR-1274a on gastric cancer
      cells. We found that miR-1274a was overexpressed in gastric cancer tissues or
      gastric cancer cells including HGC27, MGC803, AGS, and SGC-7901 by qRT-PCR
      analysis. Transfection of miR-1274a markedly promoted gastric cancer cells
      proliferation and migration as well as induced epithelial-mesenchymal transition
      (EMT) of cancer cells. Our further examination identified FOXO4 as a target of
      miR-1274a, which did not influence FOXO4 mRNA expression but significantly
      inhibited FOXO4 protein expression. Moreover, miR-1274a overexpression activated
      PI3K/Akt signaling and upregulated cyclin D1, MMP-2 and MMP-9 expressions. With
      tumor xenografts in mice models, we also showed that miR-1274a promoted
      tumorigenesis of gastric cancer in vivo. In all, our study demonstrated that miR
      1274a prompted gastric cancer cells growth and migration through dampening FOXO4
      expression thus provided a potential target for human gastric cancer therapy. 

PMID- 25753203
TI  - PKA regulates calcineurin function through the phosphorylation of RCAN1:
      identification of a novel phosphorylation site.
AB  - Calcineurin is a calcium/calmodulin-dependent phosphatase that has been
      implicated in T cell activation through the induction of nuclear factors of
      activated T cells (NFAT). We have previously suggested that endogenous regulator
      of calcineurin (RCAN1, also known as DSCR1) is targeted by protein kinase A (PKA)
      for the control of calcineurin activity. In the present study, we characterized
      the PKA-mediated phosphorylation site in RCAN1 by mass spectrometric analysis and
      revealed that PKA directly phosphorylated RCAN1 at the Ser 93. PKA-induced
      phosphorylation and the increase in the half-life of the RCAN1 protein were
      prevented by the substitution of Ser 93 with Ala (S93A). Furthermore, the PKA
      mediated phosphorylation of RCAN1 at Ser 93 potentiated the inhibition of
      calcineurin-dependent pro-inflammatory cytokine gene expression by RCAN1. Our
      results suggest the presence of a novel phosphorylation site in RCAN1 and that
      its phosphorylation influences calcineurin-dependent inflammatory target gene
      expression. 

PMID- 25753204
TI  - Dexamethasone-induced apoptosis of osteocytic and osteoblastic cells is mediated
      by TAK1 activation.
AB  - Increased apoptosis of osteoblasts and osteocytes is the main mechanism of
      glucocorticoid (GC)-induced osteonecrosis. In the current study, we investigated
      whether dexamethasone (Dex)-induced osteoblastic and osteocytic cell apoptosis is
      mediated through activation of transforming growth factor-beta (TGF-beta)
      activated kinase 1 (TAK1), and whether TAK1 inhibition could promote survival
      opposing the deleterious effects of Dex. We found that TAK1 was activated by Dex
      in both osteocytic MLO-Y4 and osteoblastic OB-6 cells, which was prevented by two
      known anti-oxidants N-acetylcysteine (NAC) and ebselen. TAK1 inhibitors,
      including LYTAK1 and 5Z-7-oxozeaenol (57-OZ), inhibited Dex-induced apoptosis of
      MLO-Y4 and OB-6 cells. Meanwhile shRNA-mediated knockdown of TAK1 also suppressed
      Dex-induced damages to MLO-Y4 and OB-6 cells. On the other hand, exogenously over
      expressing TAK1 enhanced Dex-induced MLO-Y4 and OB-6 cell apoptosis. At the
      molecular level, we found that TAK1 mediated Dex-induced pro-apoptotic Pyk2-JNK
      activation. Inhibition or silencing of TAK1 almost abolished Pyk2-JNK
      phosphorylations by Dex in MLO-Y4 and OB-6 cells. TAK1 over-expression, on the
      other hand, increased Dex's activity on Pyk2-JNK phosphorylations in above cells.
      We conclude that part of the pro-apoptotic actions of Dex on osteoblastic and
      osteocytic cells are mediated through TAK1 activation, and that inhibition of
      TAK1 might protect from GC-induced damages to osteoblasts and osteocytes. 

PMID- 25753205
TI  - A novel monoclonal antibody SMab-2 recognizes endogenous IDH2-R172S of
      chondrosarcoma.
AB  - Isocitrate dehydrogenase 2 (IDH2) mutations have been reported in gliomas,
      osteosarcomas, cartilaginous tumors, giant cell tumors of bone, and acute myeloid
      leukemias. Although IDH2 catalyzes the oxidative carboxylation of isocitrate to
      alpha-ketoglutarate (alpha-KG) in mitochondria, mutated IDH2 proteins possess the
      ability to change alpha-KG into the oncometabolite R(-)-2-hydroxyglutarate (2
      HG). To date, several monoclonal antibodies (mAbs) specific for IDH2 mutations
      have been established, such as KMab-1 against IDH2-R172K, MMab-1 against IDH2
      R172M, and WMab-1 against IDH2-R172W. Although a multi-specific mAb MsMab-1
      reacted with IDH2-R172G and IDH2-R172S, a mono-specific mAb against IDH2-R172S
      has not been established. In this study, we established a novel mAb SMab-2, which
      recognizes IDH2-R172S but not with wild type IDH2 in ELISA. Although SMab-2
      reacted with both IDH1-R132S and IDH2-R172S expressed in Escherichia coli, it
      reacted with only IDH2-R172S expressed in U-2 OS osteosarcoma cells. Furthermore,
      SMab-2 recognized endogenous IDH2-R172S protein expressed in SW1353
      chondrosarcoma cells in Western blot and immunocytochemical analyses. SMab-2 is
      expected to be useful for diagnosis of IDH2-R172S-bearing tumors. 

PMID- 25753206
TI  - WalRK two component system of Bacillus anthracis responds to temperature and
      antibiotic stress.
AB  - WalRK Two Component System (TCS) of Bacillus anthracis forms a functional TCS.
      This report elaborates upon the WalRK genomic architecture, promoter structure,
      promoter activity and expression under various stress conditions in B. anthracis.
      5' RACE located the WalRK functional promoter within 317 bp region upstream of
      WalR. Reporter gene assays demonstrated maximal promoter activity during early
      growth phases indicating utility in exponential stages of growth. qRT-PCR showed
      upregulation of WalRK transcripts during temperature and antibiotic stress.
      However, WalR overexpression did not affect the tested antibiotic MIC values in
      B. anthracis. Collectively, these results confirm that WalRK responds to cell
      envelope stress in B. anthracis. 

PMID- 25753207
TI  - Evidence for a vasomotor cyclo-oxygenase dependent mechanism of sensitization at
      the cutaneous level.
AB  - AIMS: Current-induced vasodilation (CIV) is an axon-reflex response observed
      during monopolar current application such as iontophoresis. Cyclo-oxygenase
      derivates (COD) participate in CIV and act as sensitizing agents at the anodal
      level. Mechanisms involved during cathodal current application (CCA) are
      partially unknown. In a randomized double-blind crossover trial, we tested in 16
      healthy subjects (i) the influence of the inter-stimulation interval (I-I) by
      comparing CIV following all-at-once 10 s CCA against 2 * 5 s CCA with intervals
      ranging from15 s-16 min and (ii) the participation of COD in CIV using 1 g
      aspirin or placebo intake. METHODS: Measurements were repeated 2 h and 14 days
      after treatment. Laser Doppler flowmetry assessed cutaneous blood flow, reported
      in multiples of baseline. RESULTS: Before treatment, peak vasodilation 10 min
      after the last current application (CVCstim2 ) increased compared with baseline
      whatever the I-I. Increase in CVCstim2 from baseline was greater for the 4 min
      (9.4 (5.3, 10.9) times; median (1(st) percentile, 3(rd) percentile)) and higher I
      Is compared with all-at-once delivery (3.0 (2.1, 4.3) times, P < 0.05). The
      response was similar after placebo but aspirin abolished this vasodilation
      (increase by 1.2 (1.1, 1.3) times for all-at-once delivery and by 1.5 (1.3, 1.7)
      +/- 0.3 times for 4 min interval, 2 h after aspirin intake) that recovered after
      14 days. CONCLUSIONS: This confirms the participation of COD in CIV with CCA and
      their sensitizing action. This model can represent an attractive way to study the
      axon-reflex and sensitizing function of COD in humans.

PMID- 25753208
TI  - Pulmonary resection in the treatment of life-threatening hemoptysis.
AB  - PURPOSE: Massive hemoptysis is a life threatening situation with high mortality
      rates. Surgery is effective, however generally an avoided treatment. We report
      our experience with patients undergoing lung resection for life-threatening
      hemoptysis. METHODS: Records of all surgically treated patients for hemoptysis
      between June 2009 and June 2012 were reviewed and analyzed retrospectively.
      RESULTS: Anatomical resection was performed on 31 (15.3%) patients out of 203
      patients referred to our intensive care unit for life-threatening hemoptysis. 25
      (80.6%) were male and six (19.4%) were female; with mean age of 46.4 +/- 13.7 (21
      77). Pneumonectomy was performed in four (12.9%), lobectomy in 24 (77.4%),
      segmentectomy in two (6.5%) and bilobectomy in one case. Postoperative
      complications developed in eight (25.8%), and mortality was observed in two
      (6.5%) patients. Etiology was bronchiectasis in 13 (42.0%), tuberculosis in eight
      (25.8%), carcinoma in four (12.9%), aspergilloma in four (12.9%), hydatid cyst in
      one (3.2%) and lung abscess in one (3.2%) of the cases. CONCLUSIONS: Although
      lung resection in the treatment of massive hemoptysis is accompanied with high
      morbidity and mortality rates, surgery is the only permanent curative modality.
      Acceptable results can be achived in the company of a multidisciplinary approach,
      through avoidance of pneumonectomy and urgent surgery.

PMID- 25753209
TI  - Ten years' experience in surgical treatment of right middle lobe syndrome.
AB  - PURPOSE: In this study we present the clinical, radiological, pathological,
      bronchoscopic and surgical results of 40 patients with diagnosis of middle lobe
      syndrome who were referred to our thoracic surgery unit for surgical intervention
      in a 10 years period. METHODS: Forty patients with obstructive and non
      obstructive causes of middle lobe syndrome referred to our thoracic surgery unit.
      Clinical data were collected from the patients' records in a ten years period.
      This study evaluates diagnostic approaches and surgical treatments in right
      middle lobe syndrome. RESULTS: We studied 23 females (57.5%) and 17 males (42.5%)
      with a mean age of 31.7. Clinical findings were cough 95%, sputum 80% and
      intermittent hemoptysis in 50% of patients. Middle lobe collapse was seen in CT
      scan of all patients. Bronchiectasis was the most common pathologic finding
      (55%). Tuberculosis was not rare and was final pathology in 20% of patients. In
      three patients ruptured hydatid cyst was final finding. Surgery was done without
      mortality and with only minor complications. CONCLUSION: Lobectomy of right
      middle lobe is a good therapeutic option in these patients. Due to high
      prevalence of tuberculosis and hydatid cyst in Middle Eastern countries these two
      must be considered as causes of middle lobe syndrome.

PMID- 25753210
TI  - Immune parameter analysis of children with sickle cell disease on
      hydroxycarbamide or chronic transfusion therapy.
AB  - Sickle cell disease (SCD) is increasingly appreciated as an inflammatory
      condition associated with alterations in immune phenotype and function. In this
      cross-sectional study we performed a multiparameter analysis of 18 immune markers
      in 114 paediatric SCD patients divided by treatment group [those receiving
      hydroxycrabamide (HC, previously termed hydroxyurea), chronic transfusion (CT),
      or no disease-modifying therapy] and 29 age-matched African American healthy
      controls. We found global elevation of most immune cell counts in SCD patients
      receiving no disease-modifying therapy at steady state. Despite the decrease in
      percentage of haemoglobin S associated with CT therapy, the abnormal cellular
      immune phenotype persisted in patients on CT. In contrast, in both univariate and
      multivariate analysis, treatment with HC was associated with normalization of the
      vast majority of leucocyte populations. This study provides additional support
      for HC treatment in SCD, as it appears that HC decreases the abnormally elevated
      immune cell counts in patients with SCD. 

PMID- 25753211
TI  - Effect of longer health service provider delays on stage at diagnosis and
      mortality in symptomatic breast cancer.
AB  - PURPOSE: This study explored whether longer provider delays (between first
      presentation and treatment) were associated with later stage and poorer survival
      in women with symptomatic breast cancer. METHODS: Data from 850 women with
      symptomatic breast cancer were linked with the Scottish Cancer Registry; Death
      Registry; and hospital discharge dataset. Logistic regression and Cox survival
      analyses with restricted cubic splines explored relationships between provider
      delays, stage and survival, with sequential adjustment for patient and tumour
      factors. RESULTS: Although confidence intervals were wide in both adjusted
      analyses, those with the shortest provider delays had more advanced breast cancer
      at diagnosis. Beyond approximately 20 weeks, the trend suggests longer delays are
      associated with more advanced stage, but is not statistically significant. Those
      with symptomatic breast cancer and the shortest presentation to treatment time
      (within 4 weeks) had the poorest survival. Longer time to treatment was not
      significantly associated with worsening mortality. CONCLUSIONS: Poor prognosis
      patients with breast cancer are being triaged for rapid treatment with limited
      effect on outcome. Prolonged time to treatment does not appear to be strongly
      associated with poorer outcomes for patients with breast cancer, but the power of
      this study to assess the effect of very long delays (>25 weeks) was limited.
      Efforts to reduce waiting times are important from a quality of life perspective,
      but tumour biology may often be a more important determinant of stage at
      diagnosis and survival outcome.

PMID- 25753212
TI  - A qualitative study of women's experiences of healthcare, treatment and support
      for metastatic breast cancer.
AB  - OBJECTIVE: The purpose of this qualitative research was to identify the
      healthcare, information and support needs of women living with metastatic breast
      cancer. MATERIALS AND METHODS: Semi-structured qualitative interviews were
      conducted with 18 women. Women were asked about their experiences of living with
      metastatic breast cancer and their information and support needs. RESULTS: Women
      valued relationships with their healthcare professionals, particularly their
      oncologists. They wanted more attention paid to side-effects of ongoing
      treatments, which had a negative impact on their health. While oncologists were a
      primary source of information, women also drew on other sources. There were mixed
      findings about the value of support groups, with women preferring to seek
      alternative sources of social support. CONCLUSION: A diagnosis of metastatic
      breast cancer brings heightened reliance on healthcare professionals to respond
      to women's needs in a way that is different to that required with a diagnosis of
      early breast cancer.

PMID- 25753213
TI  - The outcome of surgical treatment for elderly patients with gastric carcinoma.
AB  - BACKGROUND: The aim of this study was to clarify the operative mortality and long
      term survival of gastrectomy for elderly patients with gastric cancer. METHODS: A
      total of 461 patients who underwent gastrectomy for gastric cancer in our
      hospital were classified as elderly group (>=80 years-old, 95 patients) and
      control group (60-69 years-old, 366 patients). RESULTS: The frequency of
      comorbidities was significantly (P < 0.05) higher in elderly group (74.7%) than
      that in the control group (49.5%). No significant difference of the postoperative
      complication rate was found between the elderly group (23.2%) and the control
      group (23.2%). Adjuvant chemotherapy was 9.5% in the elderly group, which was
      significantly less than 29.0% of the control group (P < 0.05). Stage II and III
      elderly patients had worse disease specific survival (DSS) than controls did. In
      the elderly, overall survival (OS) was significantly worse than DSS in stage I
      patients (P < 0.05). CONCLUSIONS: The operative complication rate of elderly
      patients was comparable to the control group. Comorbidity and occurrence of
      secondary malignant disease should be followed for elderly patients at stage I.
      For stage II and III disease patients, a novel drug which is acceptable for the
      elderly is needed as a postoperative therapy.

PMID- 25753214
TI  - Immunohistochemical analysis of sustentacular cells in the adrenal medulla,
      carotid body and sympathetic ganglion of mice using an antibody against brain
      type fatty acid binding protein (B-FABP).
AB  - Little attention has been paid to adrenal sustentacular cells, and several major
      histology textbooks do not even describe them. This study presents a detailed
      morphological description of sustentacular cells using immuno-light microscopy
      and an antibody against brain-type fatty acid-binding protein. The immunopositive
      sustentacular cells and processes formed lattices with holes of various sizes and
      compactnesses or openness. In addition, weakly immunostained sheet-like
      structures with ill-defined contours were often associated with the processes and
      lattices. In the carotid body, which has traditionally been classified under the
      name of paraganglia in common with the adrenal medulla, immunostained
      sustentacular cell processes formed lattices in association with the weakly
      immunostained sheet-like structures, but the lattices with sheets were more
      compact and rigid than the adrenal medulla, and appeared like individually
      distinct compartments. In the ganglion, the immunostained satellite cell
      processes with the sheets tightly enclosed individual neurons. As a result, the
      immunostained sheet-like structures were regarded as en-face views of thinly
      flattened sustentacular cytoplasmic envelopes partially covering the chromaffin
      cells in the adrenal medulla, and widely in the carotid body in a way rather
      similar to the satellite cells in the ganglion. In brief, the terminal enclosing
      portions of adrenal sustentacular cell processes, in cut-views, were too
      thin/flat to be recognized as distinct lines in immuno-light microscopy because
      of its resolution limit. They are recognized in en-face views as entities of a
      substantially spacious extension in immuno-light microscopy. 

PMID- 25753215
TI  - Tubular filamentation for laser material processing.
AB  - An open challenge in the important field of femtosecond laser material processing
      is the controlled internal structuring of dielectric materials. Although the
      availability of high energy high repetition rate femtosecond lasers has led to
      many advances in this field, writing structures within transparent dielectrics at
      intensities exceeding 10(13) W/cm(2) has remained difficult as it is associated
      with significant nonlinear spatial distortion. This letter reports the existence
      of a new propagation regime for femtosecond pulses at high power that overcomes
      this challenge, associated with the generation of a hollow uniform and intense
      light tube that remains propagation invariant even at intensities associated with
      dense plasma formation. This regime is seeded from higher order nondiffracting
      Bessel beams, which carry an optical vortex charge. Numerical simulations are
      quantitatively confirmed by experiments where a novel experimental approach
      allows direct imaging of the 3D fluence distribution within transparent solids.
      We also analyze the transitions to other propagation regimes in near and far
      fields. We demonstrate how the generation of plasma in this tubular geometry can
      lead to applications in ultrafast laser material processing in terms of single
      shot index writing, and discuss how it opens important perspectives for material
      compression and filamentation guiding in atmosphere. 

PMID- 25753217
TI  - Liraglutide, the glucagon-like peptide-1 receptor agonist, has anabolic bone
      effects in diabetic Goto-Kakizaki rats.

PMID- 25753216
TI  - Low muscle mass and sarcopenia: common and predictive of osteopenia in
      inflammatory bowel disease.
AB  - BACKGROUND: Body composition is poorly studied in inflammatory bowel disease
      (IBD). Sarcopenia describes a loss of muscle mass and strength. AIM: To assess
      the prevalence of low lean mass (LM), sarcopenia and associated morbidity in an
      adult IBD cohort. METHODS: Cross-sectional data were gathered on pre-menopausal
      18- to 50-year-old patients with IBD. Whole-body dual-energy X-ray
      absorptiometry, anthropometric assessment and grip strength were performed. Low
      LM was defined as >=1 s.d. below the population mean for appendicular skeletal
      muscle index [ASMI (kg)/height (m)2], and sarcopenia as both ASMI and grip
      strength >=1 s.d. below population mean. Multivariate regression analyses were
      performed. RESULTS: Of 137 participants (median age 31 years, BMI 24.8 kg/m(2) ),
      56% were male and 69% had Crohn's disease (CD). Low LM and sarcopenia were
      observed in 21% and 12% of patients, respectively, and osteopenia/osteoporosis in
      38% of patients (mean lumbar spine t-score -0.3 +/- s.d. 1.1). Grip strength
      predicted low LM and sarcopenia better than did body mass index (BMI) (OR 4.8 vs.
      OR 0.7 for low-LM, P < 0.05 both). Normal BMI was falsely reassuring in 72% and
      76% of patients with low ASMI and sarcopenia, respectively. Low LM and sarcopenia
      (OR = 3.6, P = 0.03; OR = 6.3, P = 0.02; respectively), but not BMI nor fat mass,
      predicted osteopenia/osteoporosis. CONCLUSIONS: Low lean mass and sarcopenia are
      common in patients with IBD, and important to recognise as they predict
      osteopenia/osteoporosis. Grip strength testing should be incorporated into
      routine clinical practice to detect low lean mass deficits, which may go
      unrecognised using BMI alone.

PMID- 25753218
TI  - Forensic evaluation and population genetic study of 30 insertion/deletion
      polymorphisms in a Chinese Yi group.
AB  - Insertion/deletion polymorphisms have become a research hot spot in forensic
      science due to their tremendous potential in recent years. In the present study,
      we investigated 30 indel loci in a Chinese Yi ethnic group. The allele
      frequencies of the short allele of the 30 indel loci were in the range of 0.1025
      0.9221. The power of discrimination values were observed ranging from to 0.2630
      (HLD111 locus) to 0.6607 (HLD70 locus) and probability of exclusion values ranged
      from 0.0189 (HLD111 locus) to 0.2343 (HLD56 locus). The combined power of
      discrimination and power of exclusion for 30 loci in the studied Yi group were
      0.99999999995713 and 0.97746, respectively, which showed tremendous potential for
      forensic personal identification in the Yi group. Moreover, the DA distances,
      phylogenetic tree, principal component analysis, and cluster analysis showed the
      Yi group had close genetic relationships with the Tibetan, South Korean, Chinese
      Han, and She groups. 

PMID- 25753219
TI  - Sliding-slab three-dimensional TSE imaging with a spiral-In/Out readout.
AB  - PURPOSE: T2 -weighted imaging is of great diagnostic value in neuroimaging. Three
      dimensional (3D) Cartesian turbo spin echo (TSE) scans provide high signal-to
      noise ratio (SNR) and contiguous slice coverage. The purpose of this preliminary
      work is to implement a novel 3D spiral TSE technique with image quality
      comparable to 2D/3D Cartesian TSE. METHODS: The proposed technique uses multislab
      3D TSE imaging. To mitigate the slice boundary artifacts, a sliding-slab method
      is extended to spiral imaging. A spiral-in/out readout is adopted to minimize the
      artifacts that may be present with the conventional spiral-out readout. Phase
      errors induced by B0 eddy currents are measured and compensated to allow for the
      combination of the spiral-in and spiral-out images. A nonuniform slice encoding
      scheme is used to reduce the truncation artifacts while preserving the SNR
      performance. RESULTS: Preliminary results show that each of the individual
      measures contributes to the overall performance, and the image quality of the
      results obtained with the proposed technique is, in general, comparable to that
      of 2D or 3D Cartesian TSE. CONCLUSION: 3D sliding-slab TSE with a spiral-in/out
      readout provides good-quality T2 -weighted images, and, therefore, may become a
      promising alternative to Cartesian TSE.

PMID- 25753220
TI  - Effects of antiviral therapy for hepatitis C following treatment of
      hepatocellular carcinoma: survey findings of the Japanese Red Cross Liver Study
      Group.
AB  - AIM: To investigate, in a large number of cases at multiple institutions, the
      effects and limitations of antiviral therapy for hepatitis C following treatment
      of hepatocellular carcinoma (HCC) in clinical practice. METHODS: Retrospective
      analysis was performed of 112 patients who had received interferon (IFN) for
      treating hepatitis C following treatment of HCC and were registered with the
      Japanese Red Cross Liver Study Group. Factors that may influence recurrence and
      survival rates were investigated. RESULTS: Factors involved in prevention of
      recurrence were: surgical resection as HCC treatment, platelet and alpha
      fetoprotein (AFP) levels prior to IFN administration, IFN adherence and post-IFN
      AFP level. Multivariate analysis showed post-IFN AFP level to be an independent
      factor. Factors involved in prolonging survival were: IFN adherence, IFN response
      (sustained viral response), pre-IFN alanine aminotransferase and AFP levels, post
      IFN AFP level and absence of recurrence. Multivariate analysis showed absence of
      recurrence to be an independent factor. Although IFN adherence was involved in
      recurrence and survival, ribavirin adherence was not. IFN was suggested to be
      involved in preventing recurrence and improving survival due not only to its anti
      viral effect, but also its antitumor effect. CONCLUSION: Although complete
      prevention of HCC recurrence is difficult, the most important factor affecting
      first recurrence is the AFP level at 6 months after the conclusion of antiviral
      treatment. The survival rate improves dramatically if the hepatitis C virus is
      eliminated, but the most important factor for improving survival is absence of
      recurrence.

PMID- 25753222
TI  - Cross-Talk Between VEGF and BMP-6 Pathways Accelerates Osteogenic Differentiation
      of Human Adipose-Derived Stem Cells.
AB  - Deficiency in vascular endothelial growth factor (VEGF) or bone morphogenetic
      proteins (BMPs) results in fracture non-unions. Therefore, it is indispensable to
      comprehend the combined effect of VEGF and BMPs on the osteogenic differentiation
      of osteoprogenitor mesenchymal stem cells (MSCs) that are either naturally
      occurring at the fracture repair site or exogenously added to enhance the bone
      repair. We found that the combination of VEGF and BMP-6 enhanced COL1A2
      expression, which correlated with upregulated expression of osterix, Dlx5, and
      Msx2 in human adipose-derived stem cells (hADSCs). Cross-talk between VEGF and
      BMP-6 pathways upregulated activation of p38 mitogen-activated kinase (p38 MAPK)
      and inhibited activation of protein kinase B (PKB, also known as Akt), whereas
      phosphorylation of "mothers against decapentaplegic" homologs 1/5/8 (Smads 1/5/8)
      and extracellular signal-regulated kinases 1 and 2 (ERK 1/2) was not affected.
      Consistent with these findings, p38 inhibitor SB203580, or siRNA knockdown of
      osterix, abrogated crosstalk between the VEGF and BMP-6 pathways and
      significantly reduced the observed upregulation of COL1A2. Nuclear translocation
      of the phosphorylated form of osterix was also inhibited by SB203580. Although
      crosstalk between the VEGF-BMP-6 pathways did not show an effect on the extent of
      mineralization, inhibition of any one of the three components that were
      upregulated through the cross-talk, i.e., osterix, Dlx5, and p38 activation, led
      to a complete inhibition of mineralization. Inhibition of PKB/Akt activation,
      which is attenuated through the cross-talk, significantly enhanced ALP gene
      expression. These observations imply that crosstalk between the VEGF and BMP-6
      signaling pathways enhances osteogenic differentiation of MSCs.

PMID- 25753224
TI  - Guest editorial: Transcriptional control in myeloid cell development and related
      diseases.

PMID- 25753223
TI  - C/EBPalpha in normal and malignant myelopoiesis.
AB  - CCAAT/enhancer binding protein alpha (C/EBPalpha) dimerizes via its leucine
      zipper (LZ) domain to bind DNA via its basic region and activate transcription
      via N-terminal trans-activation domains. The activity of C/EBPalpha is modulated
      by several serine/threonine kinases and via sumoylation, its gene is activated by
      RUNX1 and additional transcription factors, its mRNA stability is modified by
      miRNAs, and its mRNA is subject to translation control that affects AUG
      selection. In addition to inducing differentiation, C/EBPalpha inhibits cell
      cycle progression and apoptosis. Within hematopoiesis, C/EBPalpha levels increase
      as long-term stem cells progress to granulocyte-monocyte progenitors (GMP).
      Absence of C/EBPalpha prevents GMP formation, and higher levels are required for
      granulopoiesis compared to monopoiesis. C/EBPalpha interacts with AP-1 proteins
      to bind hybrid DNA elements during monopoiesis, and induction of Gfi-1,
      C/EBPepsilon, KLF5, and miR-223 by C/EBPalpha enables granulopoiesis. The CEBPA
      ORF is mutated in approximately 10 % of acute myeloid leukemias (AML), leading to
      expression of N-terminally truncated C/EBPalphap30 and C-terminal, in-frame
      C/EBPalphaLZ variants, which inhibit C/EBPalpha activities but also play
      additional roles during myeloid transformation. RUNX1 mutation, CEBPA promoter
      methylation, Trib1 or Trib2-mediated C/EBPalphap42 degradation, and signaling
      pathways leading to C/EBPalpha serine 21 phosphorylation reduce C/EBPalpha
      expression or activity in additional AML cases. 

PMID- 25753226
TI  - Successful treatment of adult Langerhans cell histiocytosis with intensified
      chemotherapy.
AB  - Langerhans cell histiocytosis (LCH) is a rare disease in adults. The treatment
      strategy for this condition remains controversial. Intensified systemic
      chemotherapy is required in pediatric patients with the multiple system form of
      LCH (MS-LCH) for aggressive forms of the disease. Recent clinical trials have
      shown that intensified chemotherapy for pediatric patients diagnosed with MS-LCH
      results in improved outcomes. However, whether the feasibility and efficacy of an
      intensified systemic chemotherapy regimen are also beneficial for adult patients
      with MS-LCH remains unclear. Here, we report two cases of adult MS-LCH that were
      successfully treated with an intensified treatment protocol as used in pediatric
      patients. One patient fully completed the protocol, and has since maintained a
      complete response (CR) for 2 years following completion of the treatment. The
      other patient also achieved CR after induction therapy, and is now undergoing
      maintenance therapy in an outpatient clinic. The cases presented in this study
      suggest that intensified systemic chemotherapy as used for pediatric patients
      with MS-LCH is well tolerated and effective for adult patients as well. 

PMID- 25753227
TI  - A versatile strategy to construct multifunctional metal oxide@cyanometallate
      based coordination polymer heterostructures.
AB  - We have developed one versatile spatially confined self-assembly strategy to
      integrate cyanometallate-based coordination polymers with functional metal oxides
      into well-defined core@shell heterostructures. The structure, composition, size
      and morphology of the heterostructures could be facilely controlled. The obtained
      Fe3O4@Prussian blue heterostructure was evaluated as an appealing multifunctional
      thermal ablation agent exhibiting response to both magnetic field and light
      irradiation. 

PMID- 25753225
TI  - Lenalidomide plus low-dose dexamethasone in Chinese patients with relapsed or
      refractory multiple myeloma and renal impairment.
AB  - Lower starting doses of lenalidomide (LEN) are recommended for patients with
      renal impairment (RI). In the present study, we conducted a subgroup analysis of
      the MM-021 registration trial to investigate the efficacy and safety of LEN plus
      low-dose dexamethasone (LoDEX) in Chinese patients with advanced relapsed or
      refractory multiple myeloma (RRMM) based on levels of RI. Patients received
      LEN+LoDEX until disease progression or discontinuation. Patients were divided
      according to RI: no/mild [creatinine clearance (CrCl) >=60 mL/min, n = 131],
      moderate (CrCl >=30 to <60 mL/min, n = 54), and severe (CrCl <30 mL/min, n = 14).
      LEN starting dose was 25 mg/day on days 1-21, adjusted for baseline renal
      function. Best overall response rate was 48 %; in patients with no/mild,
      moderate, or severe RI, response rates were 50, 42, and 42 %, respectively.
      Median progression-free survival and overall survival were longer in patients
      with no/mild RI (9.3 and 22.4 months, respectively) versus those with moderate
      (6.9 and 16.0 months) or severe RI (4.8 and 11.1 months). LEN+LoDEX was well
      tolerated, although incidences of grade 3-4 neutropenia, anemia, and
      thrombocytopenia were higher in patients with severe RI. In Chinese patients with
      advanced RRMM and RI, adjusting the starting dose of LEN according to renal
      function did not compromise the efficacy or safety of LEN+LoDEX.

PMID- 25753228
TI  - Sublingual immunotherapy in children and its potential beneficial collateral
      effect on respiratory tract infections.
AB  - Although directed to the control of allergic symptoms, a possible effect of
      sublingual immunotherapy (SLIT) on susceptibility to infections has been
      hypothesized. Two hundred sixty-five children aged between 3 and 4 years of age
      affected by allergic rhinitis completed a 6 year prospective case-control study.
      One hundred forty-three children after 2 years of SLIT reported a lower
      prevalence of respiratory tract infections when compared to children not
      undergoing SLIT. 

PMID- 25753229
TI  - How intermolecular geometrical disorder affects the molecular doping of donor
      acceptor copolymers.
AB  - Molecular doping of conjugated polymers represents an important strategy for
      improving organic electronic devices. However, the widely reported low efficiency
      of doping remains a crucial limitation to obtain high performance. Here we
      investigate how charge transfer between dopant and donor-acceptor copolymers is
      affected by the spatial arrangement of the dopant molecule with respect to the
      copolymer repeat unit. We p-dope a donor-acceptor copolymer and probe its charge
      sensitive molecular vibrations in films by infrared spectroscopy. We find that,
      compared with a related homopolymer, a four times higher dopant/polymer molar
      ratio is needed to observe signatures of charges. By DFT methods, we simulate the
      vibrational spectra, moving the dopant along the copolymer backbone and finding
      that efficient charge transfer occurs only when the dopant is close to the donor
      moiety. Our results show that the donor-acceptor structure poses an obstacle to
      efficient doping, with the acceptor moiety being inactive for p-type doping. 

PMID- 25753230
TI  - New insights on the fluorescent emission spectra of Prodan and Laurdan.
AB  - Prodan and Laurdan are fluorescent probes largely used in biological systems.
      They were synthetized to be sensitive to the environment polarity, and their
      fluorescent emission spectrum shifts around 120 nm, from cyclohexane to water.
      Although accepted that their emission spectrum is composed by two emission bands,
      the origin of these two bands is still a matter of discussion. Here we analyze
      the fluorescent spectra of Prodan and Laurdan in solvents of different
      polarities, both by decomposing the spectrum into two Gaussian bands and by
      computing the Decay Associated Spectra (DAS), the latter with time resolved
      fluorescence. Our data show that the intensity of the lower energy emission band
      of Prodan and Laurdan (attributed, in the literature, to the decay of a solvent
      relaxed state) is higher in cyclohexane than in water, showing a decrease as the
      polarity of the medium increases. Moreover, in all solvents studied here, the
      balance between the two emission bands is not dependent on the temperature,
      strongly suggesting two independent excited states. Both bands were found to
      display a red shift as the medium polarity increases. We propose here a new
      interpretation for the two emission bands of Prodan and Laurdan in homogeneous
      solvents: they would be related to the emission of two independent states, and
      not to a pair of non-relaxed and solvent relaxed states. 

PMID- 25753231
TI  - Fluorescence Study of Eu-YVO4 Nano-Phosphors as a Function of Calcination
      Temperature and Excitation Wavelengths.
AB  - Nano phosphors have been prepared with 1 mol% and 5 mol% doping of Eu in vanadate
      by sol-gel method. X-ray pattern indicated that nano phosphors did not lead to
      phase change and has tetragonal crystal structure. Excitation spectra revealed
      that the band at 308 nm arises due to the charge transfer transitions among
      Eu(3+) and VO4 (3-) ions. The peak position of fluorescence shifted from 518 to
      638 nm on varying the excitation wavelength from 257 nm to 318 nm. It is also
      noticed that the fluorescence intensity increases with the rise of calcination
      temperatures of the samples.

PMID- 25753232
TI  - Minimally Invasive Transforaminal Lumbar Interbody Fusion (TLIF) for
      Spondylolisthesis in 282 Patients: In Situ Arthrodesis versus Reduction.
AB  - OBJECTIVE: The benefits of spondylolisthesis reduction via minimally invasive
      transforaminal lumbar interbody fusion (MI-TLIF) remain poorly understood. The
      purpose was to compare the complications, perioperative factors, and fusion rates
      in patients undergoing MI-TLIF for degenerative spondylolisthesis between those
      in whom reduction was or was not performed. METHODS:  INCLUSION CRITERIA: 1)
      patients who underwent a 1, 2, or 3 level MI-TLIF and 2) had a preoperative
      diagnosis of degenerative spondylolisthesis (Meyerding grade >0). EXCLUSION
      CRITERIA: >10 degrees  coronal curves, significant sagittal malalignment,
      infection, and preoperative hardware failure. Patients were grouped on the basis
      of those who underwent reduction of the spondylolisthesis by at least 1 Meyerding
      grade (RED) and those who did not (NORED). RESULTS: A total of 282 patients were
      included: RED (162, 57.4%) and NORED (120, 42.6%). Mean ages (61.68 +/- 10.43 vs.
      61.88 +/- 11.76 years, respectively, P > 0.05) and operative times (P > 0.05)
      were statistically similar. RED had a significantly larger EBL (280.2 +/- 24.03
      vs. 212.61 +/- 17.54, P < 0.05). The length of hospital stay, intraoperative
      complications, postoperative medical and surgical complications, and disposition
      were statistically similar between groups (P > 0.05, for all). RED had a
      significantly higher percentage of patients with a successful fusion at 1 year
      than NORED (84.50% vs. 70.83%, P < 0.05). CONCLUSION: Reduction of
      spondylolisthesis was not associated with an increase in operative time, length
      of stay, and perioperative and postoperative complications compared with fusion
      in situ. Reduction was associated with higher blood loss but also a higher rate
      of fusion success at 1 year. Overall, reduction did not incur additional risk and
      had positive perioperative outcomes.

PMID- 25753233
TI  - Morphological-Hemodynamic Characteristics of Intracranial Bifurcation Mirror
      Aneurysms.
AB  - BACKGROUND: Many morphological and hemodynamic parameters have been proposed as
      promising aneurysm rupture status discriminators. Besides, a clear dichotomy
      between sidewall and bifurcation aneurysms was reported. In this study, we strove
      to evaluate the contribution of many reported morphological and hemodynamic
      parameters to retrospective rupture status determination in bifurcation aneurysms
      independent of patients' characteristics. METHODS: Computational fluid dynamics
      were performed on 16 patients with bifurcation mirror aneurysms (MANs). Each pair
      was divided into ruptured and unruptured groups. The morphological and
      hemodynamic factors were analyzed and compared. Receiver operating
      characteristics (ROC) analysis was performed, and the area under the ROC curve
      (AUC) was calculated for all parameters to quantify the predictability of each
      index and identify the optimal threshold. RESULTS: Morphological (size, aspect
      ratio, size ratio, and height-width ratio) and hemodynamic (time-averaged mean
      wall shear stress [WSSmean], low WSS area [LSA]) parameters reached statistical
      significance (P < 0.05). Aneurysm irregular shape, oscillatory shear index (OSI),
      flow stability, inflow concentration, and impingement zone did not achieve
      significantly statistical differences (P = 0.508, P = 0.319, P = 0.523, P =
      0.227, and P = 1.000, respectively). After ROC analysis, only aspect ratio and
      LSA had excellent AUC values (0.840 and 0.824, respectively). Other key
      parameters, including size, size ratio, height-width ratio, and WSSmean, had AUC
      values between 0.7 and 0.8 (0.730, 0.715, 0.703, 0.727, respectively).
      CONCLUSIONS: Higher aspect ratio and LSA are good indicators for bifurcation
      aneurysm rupture. MANs with different rupture status might be a useful disease
      model in which many factors are balanced to investigate possible features linked
      to aneurysm rupture.

PMID- 25753234
TI  - Cerebral Arteriovenous Malformations and Epilepsy, Part 1: Predictors of Seizure
      Presentation.
AB  - OBJECTIVE: Seizures are relatively common in patients harboring cerebral
      arteriovenous malformations (AVMs). Because the pathogenesis of AVM-associated
      epilepsy is not well-defined, we aim to determine the factors associated with
      seizure presentation in AVM patients. METHODS: We evaluated our institutional AVM
      radiosurgery database, from 1989-2013, to select patients in whom pertinent
      clinical information at presentation and adequate clinical and radiologic follow
      up was available. Baseline patient demographics and AVM angioarchitectural
      features were compared between patients with and without seizure presentation. In
      addition to standard descriptive statistics, logistic regression analyses were
      performed to identify predictors of seizure presentation. RESULTS: Of the 1007
      AVM patients included for analysis, 229 patients presented with seizures (22.7%).
      The incidence of seizure presentation was significantly higher in cortical than
      noncortical AVMs (33.1% vs. 6.6%, P < 0.0001). Among the cortical locations,
      occipital AVMs had the lowest rate of seizure presentation (21.5%, P = 0.0012),
      whereas the rates of seizure presentation in frontal (37.3%), temporal (37.7%),
      and parietal (34.0%) AVMs were similar. The lack of prior AVM hemorrhage (P <
      0.0001), larger nidus diameter (P < 0.0001), and cortical location (P < 0.0001)
      were independent predictors of seizure presentation in the multivariate analysis.
      The strongest independent predictors of seizure presentation were lack of prior
      AVM hemorrhage (OR 16.8) and cortical location (OR 4.2). CONCLUSIONS: Large,
      unruptured, cortical nidi are most prone to seizure presentation in patients
      referred for radiosurgery. Further investigations of the molecular biology,
      neuronal and glial physiology, and natural history of AVM-associated epilepsy
      appear warranted.

PMID- 25753235
TI  - Neuro-ophthalmic Assessment in Unruptured Intracranial Aneurysms.

PMID- 25753236
TI  - Skull Trepanations in Bronze Age Greece: An Archaeologist's View.

PMID- 25753237
TI  - Intramedullary Solitary Fibrous Tumor--A Benign Form of Hemangiopericytoma? Case
      Report and Review of the Literature.
AB  - BACKGROUND: Solitary fibrous tumors (SFTs) are benign tumors of the soft tissue
      occurring anywhere in the human body but arise predominantly in the visceral
      pleura. SFTs of the central nervous system are rare, especially when they occur
      within the spinal cord. CASE DESCRIPTION: We present a case of an 83-year-old
      female patient presenting with acute spastic paralysis of the lower extremities
      after a history of progressive weakness and incontinence. Magnetic resonance
      imaging (MRI) findings were typical for meningioma, but an intradural, mainly
      intramedullary tumor was found at the first operation. A second operation was
      performed under neurophysiological monitoring, and complete removal of the tumor
      was achieved. Neurological conditions improved after the procedure, but the
      patient remained paraparetic. Histological and immunohistochemical findings
      revealed an SFT. CONCLUSIONS: There is evidence that SFTs and hemangiopericytomas
      (HPCs) are not different entities but should be considered as different
      graduations of a common spectrum. The extent of resection is a prognostic factor
      for recurrence-free survival in SFT; therefore we recommend surgery with complete
      resection whenever possible depending on the results of mandatory intraoperative
      neurophysiological monitoring in these cases.

PMID- 25753246
TI  - Metabolic roles of PGC-1alpha and its implications for type 2 diabetes.
AB  - PGC-1alpha is a transcriptional coactivator expressed in brown adipose tissue,
      liver, pancreas, kidney, skeletal and cardiac muscles, and the brain. This review
      presents data illustrating how PGC-1alpha regulates metabolic adaptations and
      participates in the aetiology of type 2 diabetes (T2D). Studies in mice have
      shown that increased PGC-1alpha expression may be beneficial or deleterious,
      depending on the tissue: in adipose tissue, it promotes thermogenesis and thus
      protects against energy overload, such as seen in diabetes and obesity; in
      muscle, PGC-1alpha induces a change of phenotype towards oxidative metabolism. In
      contrast, its role is clearly deleterious in the liver and pancreas, where it
      induces hepatic glucose production and inhibits insulin secretion, changes that
      promote diabetes. Previous studies by our group have also demonstrated the role
      of PGC-1alpha in the fetal origins of T2D. Overexpression of PGC-1alpha in beta
      cells during fetal life in mice is sufficient to induce beta-cell dysfunction in
      adults, leading to glucose intolerance. PGC-1alpha also is associated with
      glucocorticoid receptors in repressing expression of Pdx1, a key beta-cell
      transcription factor. In conclusion, PGC-1alpha participates in the onset of
      diabetes through regulation of major metabolic tissues. Yet, it may not represent
      a useful target for therapeutic strategies against diabetes as it exerts both
      beneficial and deleterious actions on glucose homoeostasis, and because PGC
      1alpha modulation is involved in neurodegenerative diseases. However, its role in
      cellular adaptation shows that greater comprehension of PGC-1alpha actions is
      needed. 

PMID- 25753247
TI  - An immunohistochemical study of potential diagnostic and therapeutic biomarkers
      of wild-type gastrointestinal stromal tumours.

PMID- 25753245
TI  - High-sensitivity C-reactive protein does not improve the differential diagnosis
      of HNF1A-MODY and familial young-onset type 2 diabetes: A grey zone analysis.
AB  - AIM: Low plasma levels of high-sensitivity C-reactive protein (hs-CRP) have been
      suggested to differentiate hepatocyte nuclear factor 1 alpha-maturity-onset
      diabetes of the young (HNF1A-MODY) from type 2 diabetes (T2D). Yet, differential
      diagnosis of HNF1A-MODY and familial young-onset type 2 diabetes (F-YT2D) remains
      a difficult challenge. Thus, this study assessed the added value of hs-CRP to
      distinguish between the two conditions. METHODS: This prospective multicentre
      study included 143 HNF1A-MODY patients, 310 patients with a clinical history
      suggestive of HNF1A-MODY, but not confirmed genetically (F-YT2D), and 215
      patients with T2D. The ability of models, including clinical characteristics and
      hs-CRP to predict HNF1A-MODY was analyzed, using the area of the receiver
      operating characteristic (AUROC) curve, and a grey zone approach was used to
      evaluate these models in clinical practice. RESULTS: Median hs-CRP values were
      lower in HNF1A-MODY (0.25mg/L) than in F-YT2D (1.14mg/L) and T2D (1.70mg/L)
      patients. Clinical parameters were sufficient to differentiate HNF1A-MODY from
      classical T2D (AUROC: 0.99). AUROC analyses to distinguish HNF1A-MODY from F-YT2D
      were 0.82 for clinical features and 0.87 after including hs-CRP. For the grey
      zone analysis, the lower boundary was set to miss<1.5% of true positives in non
      tested subjects, while the upper boundary was set to perform 50% of genetic tests
      in individuals with no HNF1A mutation. On comparing HNF1A-MODY with F-YT2D, 65%
      of patients were classified in between these categories - in the zone of
      diagnostic uncertainty - even after adding hs-CRP to clinical parameters.
      CONCLUSION: hs-CRP does not improve the differential diagnosis of HNF1A-MODY and
      F-YT2D.

PMID- 25753248
TI  - DIFFERENCES IN ILLNESS REPRESENTATIONS IN PATIENTS WITH CHRONIC KIDNEY DISEASE.
AB  - OBJECTIVE: To explore the impact of chronic kidney disease (CKD) on individual
      illness representations, including symptoms and causal attributions. DESIGN AND
      MEASURES: Fifty-four patients responded to the Illness Perception Questionnaire
      (IPQ-R) and a further seven patients undertook cognitive interviews regarding the
      IPQ-R. All respondents had CKD stage 2-5, not undergoing renal replacement
      therapy. RESULTS: Those in earlier CKD stages and those with fewer symptoms
      perceived a significantly different understanding of their condition than those
      in more advanced disease stages or with more symptoms. Behavioural and
      psychological attributions were commonly referred to as contributing causes to
      CKD. These attributions were associated to negative illness representations. An
      uncertainty assessing symptoms attributed to CKD was indicated, especially in
      earlier disease stages. CONCLUSION: Illness representations differ with CKD
      stages and symptom burden. The patients in earlier disease stages or with fewer
      symptoms did not hold as strong beliefs about their illness as being a threat as
      those in advanced stages or with more symptoms. Self-blame emerged as a common
      causal attribution. Patients did not always relate symptoms to CKD, therefore
      this study identifies a gap in patients' disease knowledge, especially in earlier
      stages of the condition.

PMID- 25753249
TI  - Diagnostic accuracy of (18)F-FDG-PET/CT in early and late stages of high-risk
      cutaneous malignant melanoma.
AB  - BACKGROUND: The precise role of total body (18) F-fluorodeoxyglucose-positron
      emission tomography/computed tomography (PET/CT) in the clinical management of
      patients with cutaneous malignant melanoma (CMM) is not well established.
      OBJECTIVE: The purpose of this study was to investigate the diagnostic accuracy
      of PET/CT in early- and late-stage patients with high-risk CMM. METHODS: We
      retrospectively analysed various imaging, histopathological and clinical data
      from 97 patients also examined by PET/CT during a 5-year period (2007-2011).
      Three groups were assessed: stage I/II, resected stage III and unresectable stage
      III/stage IV. RESULTS: The median follow-up time of living patients was 43.48 +/-
      19.67 (15-142) months. We observed a high diagnostic accuracy in all stages
      (91.3%, 92.5% and 96.2% respectively). PET/CT appeared to be reliable diagnostic
      tool even for the detection of small lymph node metastases. PET/CT was
      informative in 14 of 19 cases wherein another imaging examination provided
      inconclusive results regarding lesion dignity. However, PET/CT was less suitable
      for properly evaluating the dignity of a lung lesion. A true positive scan was
      twice as likely in clinically negative patients with resected stage III disease
      than in patients with stage I/II disease (35.9% and 14.5%, P = 0.007).
      CONCLUSIONS: These results confirm that PET/CT is an important diagnostic tool in
      the management of patients with high-risk CMM, but it cannot replace the standard
      of care examinations. More accurate clinicopathological and timing criteria must
      be defined to best utilize the advantages of this imaging method.

PMID- 25753251
TI  - Climate impacts on transocean dispersal and habitat in gray whales from the
      Pleistocene to 2100.
AB  - Arctic animals face dramatic habitat alteration due to ongoing climate change.
      Understanding how such species have responded to past glacial cycles can help us
      forecast their response to today's changing climate. Gray whales are among those
      marine species likely to be strongly affected by Arctic climate change, but a
      thorough analysis of past climate impacts on this species has been complicated by
      lack of information about an extinct population in the Atlantic. While little is
      known about the history of Atlantic gray whales or their relationship to the
      extant Pacific population, the extirpation of the Atlantic population during
      historical times has been attributed to whaling. We used a combination of ancient
      and modern DNA, radiocarbon dating and predictive habitat modelling to better
      understand the distribution of gray whales during the Pleistocene and Holocene.
      Our results reveal that dispersal between the Pacific and Atlantic was climate
      dependent and occurred both during the Pleistocene prior to the last glacial
      period and the early Holocene immediately following the opening of the Bering
      Strait. Genetic diversity in the Atlantic declined over an extended interval that
      predates the period of intensive commercial whaling, indicating this decline may
      have been precipitated by Holocene climate or other ecological causes. These
      first genetic data for Atlantic gray whales, particularly when combined with
      predictive habitat models for the year 2100, suggest that two recent sightings of
      gray whales in the Atlantic may represent the beginning of the expansion of this
      species' habitat beyond its currently realized range.

PMID- 25753250
TI  - Psychosocial perspectives on sexual recovery after prostate cancer treatment.
AB  - Many therapies for erectile dysfunction (ED) after prostate cancer treatment
      improve erectile firmness, yet, most couples stop using aids within 1-2 years.
      Patients and partners who expect immediate and complete success with their first
      ED treatment can be demoralized when they experience treatment failure, which
      contributes to reticence to explore other ED aids. Comprehensive patient
      education should improve sustainability and satisfaction with ED treatments. Pre
      emptive and realistic information should be provided to couples about the
      probability of recovering natural erections. Beginning intervention early and
      using a couple-based approach is ideal. Recommendations are provided about the
      timing of ED treatment, the order of aid introduction, and combination therapies.
      Renegotiation of sexual activity is an essential part of sexual adaptation. From
      the outset of therapy, couples should be encouraged to broaden their sexual
      repertoire, incorporate erection-independent sexual activities, and continue to
      be sexual despite ED and reduced libido. 

PMID- 25753252
TI  - The effects of pituitary and thyroid disorders on haemostasis: potential clinical
      implications.
AB  - Disturbances of coagulation and fibrinolysis are usually multifactorial and
      growing evidence suggests that endocrinopathies modulate the haemostatic balance.
      The thrombotic alterations in endocrine disorders range from mild laboratory
      clotting abnormalities with little clinical significance to serious thrombotic
      and bleeding disorders directly related to hormonal disturbances. This literature
      review focuses on presenting the current data on the effects of thyroid and
      pituitary disorders on various parameters of the haemostatic system. With the
      exception of overt hypothyroidism which appears to cause a bleeding tendency, the
      rest of the endocrinopathies discussed in this review (subclinical
      hypothyroidism, hyperthyroidism, endogenous hypercortisolaemia, growth hormone
      deficiency, acromegaly, prolactinoma/hyperprolactinaemia and hypogonadotrophic
      hypogonadism) are associated with a hypercoagulable and hypofibrinolytic state,
      increasing the overall cardiovascular risk and thromboembolic potential in these
      patients. In most studies, the haemostatic abnormalities seen in endocrine
      disorders are usually reversible with successful treatment of the underlying
      condition and biochemical disease remission. High-quality studies on larger
      patient cohorts are needed to produce robust evidence on the effects of endocrine
      disorders and their therapeutic interventions on coagulation and fibrinolysis, as
      well as on the long-term mortality and morbidity outcomes in association with
      endocrine-related haemostatic imbalance. Given the rarity of some of the
      endocrine disorders, multicentre studies are required to achieve this target.

PMID- 25753253
TI  - Unravelling RNA-substrate interactions in a ribozyme-catalysed reaction using
      fluorescent turn-on probes.
AB  - The Diels-Alder reaction is one of the most important C-C bond-forming reactions
      in organic chemistry, and much effort has been devoted to controlling its enantio
      and diastereoselectivity. The Diels-Alderase ribozyme (DAse) catalyses the
      reaction between anthracene dienes and maleimide dienophiles with multiple
      turnover, stereoselectivity, and up to 1100-fold rate acceleration. Here, a new
      generation of anthracene-BODIPY-based fluorescent probes was developed to monitor
      catalysis by the DAse. The brightness of these probes increases up to 93-fold
      upon reaction with N-pentylmaleimide (NPM), making these useful tools for
      investigating the stereochemistry of the ribozyme-catalysed reaction. With these
      probes, we observed that the DAse catalyses the reaction with >91% de and >99%
      ee. The stereochemistry of the major product was determined unambiguously by
      rotating-frame nuclear Overhauser NMR spectroscopy (ROESY-NMR) and is in
      agreement with crystallographic structure information. The pronounced
      fluorescence change of the probes furthermore allowed a complete kinetic
      analysis, which revealed an ordered bi uni type reaction mechanism, with the
      dienophile binding first.

PMID- 25753254
TI  - Efficient strategies to find diagnostic test accuracy studies in kidney journals.
AB  - AIM: Nephrologists looking for quick answers to diagnostic clinical questions in
      MEDLINE can use a range of published search strategies or Clinical Query limits
      to improve the precision of their searches. We aimed to evaluate existing search
      strategies for finding diagnostic test accuracy studies in nephrology journals.
      METHODS: We assessed the accuracy of 14 search strategies for retrieving
      diagnostic test accuracy studies from three nephrology journals indexed in
      MEDLINE. Two investigators hand searched the same journals to create a reference
      set of diagnostic test accuracy studies to compare search strategy results
      against. RESULTS: We identified 103 diagnostic test accuracy studies, accounting
      for 2.1% of all studies published. The most specific search strategy was the
      Narrow Clinical Queries limit (sensitivity: 0.20, 95% CI 0.13-0.29; specificity:
      0.99, 95% CI 0.99-0.99). Using the Narrow Clinical Queries limit, a searcher
      would need to screen three (95% CI 2-6) articles to find one diagnostic study.
      The most sensitive search strategy was van der Weijden 1999 Extended
      (sensitivity: 0.95; 95% CI 0.89-0.98; specificity 0.55, 95% CI 0.53-0.56) but
      required a searcher to screen 24 (95% CI 23-26) articles to find one diagnostic
      study. Bachmann 2002 was the best balanced search strategy, which was sensitive
      (0.88, 95% CI 0.81-0.94), but also specific (0.74, 95% CI 0.73-0.75), with a
      number needed to screen of 15 (95% CI 14-17). CONCLUSION: Diagnostic studies are
      infrequently published in nephrology journals. The addition of a strategy for
      diagnostic studies to a subject search strategy in MEDLINE may reduce the records
      needed to screen while preserving adequate search sensitivity for routine
      clinical use.

PMID- 25753255
TI  - Serum creatinine and alkaline phosphatase levels are associated with severe
      chronic periodontitis.
AB  - BACKGROUND AND OBJECTIVE: Periodontitis may alter systemic homeostasis and
      influence creatinine and alkaline phosphatase levels. Therefore, the aim of this
      study was to evaluate the relationship between severe chronic periodontitis and
      serum creatinine and alkaline phosphatase levels. MATERIAL AND METHODS: One
      hundred patients were evaluated, 66 with severe chronic periodontitis (test
      group) and 34 periodontally healthy controls (control group). Medical,
      demographic and periodontal parameters were registered. Blood sample was
      collected after an overnight fast and serum creatinine and alkaline phosphatase
      levels were determined. RESULTS: There were significant differences between test
      and control groups in ethnicity, gender and educational level (p < 0.05).
      Patients with periodontitis showed a lower mean creatinine level (p < 0.05) and
      higher mean alkaline phosphatase level (p < 0.001) than the control group. There
      were significant correlations between periodontal parameters and serum creatinine
      and alkaline phosphatase levels. CONCLUSION: Severe chronic periodontitis was
      associated to lower creatinine and higher alkaline phosphatase levels.

PMID- 25753256
TI  - Reduction of 30-Day Preventable Pediatric Readmission Rates With Postdischarge
      Phone Calls Utilizing a Patient- and Family-Centered Care Approach.
AB  - INTRODUCTION: The purpose of this project was to evaluate the effectiveness of
      postdischarge phone calls on 30-day preventable readmission rates within the
      pediatric hospital setting. Because the unit of care identified was patients and
      their families, a patient- and family-centered care approach was used. METHOD:
      The project used an exploratory design and was conducted at a 154-bed pediatric
      hospital facility. A sample of 15 patients meeting project inclusion criteria was
      selected before and after the intervention, and medical records were reviewed to
      identify if a 30-day preventable readmission had occurred. RESULTS: Medical
      record review revealed four preintervention readmissions, providing an overall
      preintervention readmission rate of 26%. Only one readmission was discovered
      after the intervention, yielding an overall postintervention readmission rate of
      6%. DISCUSSION: The sample size was not large enough to show statistical
      significance, but clinical significance was seen, with readmission rates for the
      project target population decreasing below the rates recorded in 2012.

PMID- 25753258
TI  - Decreased TCF7L2 protein levels in type 2 diabetes mellitus correlate with
      downregulation of GIP- and GLP-1 receptors and impaired beta-cell function.
AB  - In this article, Figure 2F was incorrect. The correct panel is shown below. The
      authors sincerely apologise for this error.

PMID- 25753257
TI  - Metastatic behaviour of sinonasal adenocarcinomas of the intestinal type (ITAC).
AB  - The relative frequency of regional lymphogenic versus distant hematogenic
      metastases was evaluated in 369 patients with sinonasal adenocarcinoma of the
      intestinal type (ITAC). We assessed the results of neck dissections for a limited
      number of patients undergoing this surgical intervention. 117 ITAC patients were
      followed up for at least 5 years. Neck dissections were performed in 18 cases (15
      primary and 3 secondary operations), 4 of which revealed carcinoma-positive lymph
      nodes. Metastases in lymph nodes were also diagnosed clinically in three other
      patients adding up to a total of seven individuals (6 % of 117) with lymphogenic
      metastases. In comparison, distant hematogenic metastases were identified in 15.4
      % of these 117 patients. In the second group of 252 patients, the occurrence of
      distant hematogenic metastases and colorectal adenocarcinomas was registered but
      no formal follow-up procedure was applied. 50 neck dissections were performed in
      this group, 46 of which exhibited no histological evidence for metastases in
      lymph nodes, while in 1 case they were carcinoma-positive. Three additional cases
      showed clinical signs of metastases in regional lymph nodes. Taken together, our
      observations indicate that regional lymphogenic metastases are rather rare (about
      2 %) in patients with sinonasal adenocarcinoma of the intestinal type. Therefore,
      the surgery of neck dissection appears not advised as routine intervention in
      these cases. ITAC patients show a normal prevalence of colorectal
      adenocarcinomas.

PMID- 25753259
TI  - The effect of dissolved oxygen on the susceptibility of blood.
AB  - PURPOSE: It has been predicted that, during hyperoxia, excess O2 dissolved in
      arterial blood will significantly alter the blood's magnetic susceptibility. This
      would confound the interpretation of the hyperoxia-induced blood oxygenation
      level-dependent signal as arising solely from changes in deoxyhemoglobin. This
      study, therefore, aimed to determine how dissolved O2 affects the susceptibility
      of blood. THEORY AND METHODS: We present a comprehensive model for the effect of
      dissolved O2 on the susceptibility of blood and compare it with another recently
      published model, referred to here as the ideal gas model (IGM). For validation,
      distilled water and samples of bovine plasma were oxygenated over a range of
      hyperoxic O2 concentrations and their susceptibilities were determined using
      multiecho gradient echo phase imaging. RESULTS: In distilled water and plasma,
      the measured changes in susceptibility were very linear, with identical slopes of
      0.062 ppb/mm Hg of O2. This change was dramatically less than previously
      predicted using the IGM and was close to that predicted by our model. The primary
      source of error in the IGM is the overestimation of the volume fraction occupied
      by dissolved O2. CONCLUSION: Under most physiological conditions, the
      susceptibility of dissolved O2 can be disregarded in MRI studies employing
      hyperoxia.

PMID- 25753260
TI  - Thymic stromal lymphopoietin deficiency attenuates experimental autoimmune
      encephalomyelitis.
AB  - In the present study we examined the role of thymic stromal lymphopoietin (TSLP)
      in experimental autoimmune encephalomyelitis (EAE). Here, we report that TSLP
      knock-out (KO) mice display a delayed onset of disease and an attenuated form of
      EAE. This delayed onset was accompanied by a reduced number of encephalitogenic T
      helper type 1 (Th1) cells in the central nervous system (CNS) of TSLP KO mice. In
      addition, CD4(+) and CD8(+) T cells from CNS of TSLP KO mice show a reduced
      activation status in comparison to wild-type mice. It is noteworthy that we could
      also show that lymph node cells from TSLP KO mice expanded less efficiently and
      that interleukin (IL)-6-, interferon (IFN)-gamma and tumour necrosis factor (TNF)
      alpha levels were reduced. Furthermore, CD3(+) T cells isolated in the
      preclinical phase from myelin oligodendrocyte glycoprotein peptide 35-55 (MOG(35
      55))-immunized TSLP KO mice showed a reduced response after secondary exposure to
      MOG(35-55), indicating that differentiation of naive T cells into MOG(35-55)
      specific effector and memory T cells was impaired in KO mice. The addition of
      recombinant TSLP enhanced T cell proliferation during MOG(35-55) restimulation,
      showing that T cells also respond directly to TSLP. In summary, these data
      demonstrate that expression of, and immune activation by, TSLP contributes
      significantly to the immunopathology of EAE.

PMID- 25753261
TI  - Passive reporting greatly underestimates the rate of transfusion-associated
      circulatory overload after platelet transfusion.
AB  - BACKGROUND: Transfusion-associated circulatory overload (TACO) is the second
      leading cause of reported transfusion-related fatalities in the United States.
      While its occurrence has been previously investigated after red cell and plasma
      transfusion, no data are available regarding its association with platelet
      transfusion. Our goal was to determine the rate of platelet-associated TACO at
      our university medical centre. STUDY DESIGN AND METHODS: This study had
      retrospective and prospective analyses. The 13-year retrospective analysis served
      to determine the historical rate of platelet-associated TACO by passive
      reporting. The 30-day prospective analysis included active surveillance of all
      non-emergently issued and non-operative platelet recipients >=16 years old with
      no transfusions in the previous 6 h determined by analysis of blood bank product
      issue records. Data collected included demographics, vital signs pre- and
      posttransfusion, fluid balances, supplemental oxygen use, reports of dyspnoea,
      and infusion rates. For the prospective analysis, all variables were collected
      within 24 h of transfusion from the medical record and, when necessary,
      interviews with care providers and/or patients. RESULTS: In the retrospective
      analysis, 366 reactions were reported, of which 6 (1.6%) were TACO. The
      historical rate of TACO was 1:5997 transfused platelet units. During the
      prospective analysis, 225 eligible patients received a total of 334 units of
      platelets. The average platelet transfusion volume was 261 +/- 26 ml, and the
      average infusion rate was 391 +/- 198 ml/h. Two unreported TACO reactions were
      discovered and characterized by new-onset hypertension, crackles on lung
      auscultation, dyspnoea, hypoxia and supplemental oxygen requirements which
      resolved completely with diuresis. The rate of TACO during this prospective
      analysis was 1:167 transfused platelet units. CONCLUSION: Platelet-associated
      TACO is greatly underestimated by passive reporting in the adult patient
      population.

PMID- 25753262
TI  - Unilateral keratosis pilaris occurring on linear hypopigmentation patches: a new
      variant of keratosis pilaris in an Asian?

PMID- 25753263
TI  - Portal hypertension caused by right common iliac artery-superior mesenteric vein
      fistula.
AB  - Portal hypertension caused by arterio-portal fistula between the right common
      iliac artery and superior mesenteric vein has not been reported. Here, we report
      such a case in a 35-year-old male without any history of liver disease or
      abdominal trauma. This case was confirmed by abdominal aorta angiography and
      three-dimensional angiography, and was successfully treated by a covered stent
      implantation in the right common iliac artery to block the fistula. 

PMID- 25753264
TI  - Developmental origins of flatter cortisol rhythms: socioeconomic status and adult
      cortisol activity.
AB  - OBJECTIVE: Low socioeconomic status (SES) is associated with increased
      psychosocial stress among low-income persons, which could contribute to
      differences in activity of the HPA axis (assessed by diurnal cortisol profiles).
      The current article investigates associations of SES from different developmental
      stages with cortisol profiles. METHODS: Using data from a large,
      socioeconomically diverse birth cohort (N = 1,490) in Cebu, Philippines, the
      current study compares the relative and joint contributions of SES from five
      developmental periods, between the prenatal/birth period and early adulthood, to
      adult cortisol, and examines the effects of chronic exposure to low SES. RESULTS:
      Chronically low SES from infancy through early adulthood predicts the highest
      bedtime cortisol levels, lowest cortisol awakening responses (CARs), lowest total
      cortisol levels across the day (area under curve or AUC), and the flattest
      cortisol rhythms between wake up and bedtime, a profile associated with poorer
      health. Results indicate that cumulative economic strain (between the prenatal
      period and early adulthood) predicts flatter cortisol rhythms more consistently
      than SES from any particular period. CONCLUSION: Interventions focusing on the
      psychosocial stressors associated with economic deprivation during any period
      from infancy to adulthood may be helpful, but targeting interventions across
      multiple periods may have the greatest impact. Interventions aimed at improving
      economic conditions between infancy and early adulthood may have implications for
      long-term changes in HPA axis functioning.

PMID- 25753265
TI  - Compliance with pregnancy prevention plan recommendations in 8672 French women of
      childbearing potential exposed to acitretin.
AB  - PURPOSE: Acitretin is an oral synthetic aromatic analogue of retinoic acid
      available in most European countries since 1988. It is mainly used to treat
      severe psoriasis. Like all systemic retinoids, acitretin is teratogenic. Strict
      pregnancy prevention is required in women of childbearing potential who use
      acitretin. This study assessed compliance with Pregnancy Prevention Plan (PPP)
      recommendations, specifically looking at compliance with pregnancy testing (PT)
      and pregnancy occurrence. METHODS: A cohort of 8672 women aged 15-49 years
      initiating acitretin treatment from 1 January 2007 through 31 December 2013 was
      identified using French SNIIRAM (administrative claims data) and PMSI
      (hospitalisations data) databases. Pregnancy tests (PTs) were identified from
      reimbursed serum betaHCG and urine laboratory PTs. To satisfy PT criteria,
      patients who started treatment had to undergo a PT within 3 days before acitretin
      was dispensed. Pregnancies were identified by a pregnancy-related hospital stay
      or an outpatient medical abortion. RESULTS: A PT was performed in only 12% of
      women starting treatment and was rarely performed during treatment or during the
      24 months following discontinuation of treatment. Compliance with PPP
      recommendations although poor appeared to be better among private dermatologists,
      as a PT was performed for 16% of treatment initiations (vs. 4% for general
      practitioners, p < 0.001). Moreover, 470 pregnancies were reported corresponding
      to 27 pregnancies per 1000 person-years at risk of teratogenicity. CONCLUSIONS:
      This study highlights poor compliance with acitretin PPP recommendations in
      France. Physicians and pharmacists must more rigorously apply the acitretin PPP
      recommendations, and patients must be better informed about acitretin's risk of
      teratogenicity.

PMID- 25753267
TI  - MHCI and CD8 lineage commitment. Prolonged access to thymic epithelial MHCI seals
      CD8+ lineage commitment.

PMID- 25753266
TI  - Moving to the suburbs: T-cell positioning within lymph nodes during activation
      and memory.
AB  - Lymph nodes are highly organized secondary lymphoid structures crucial for the
      initiation of immune responses. Naive T cells are strategically located within
      lymph nodes to optimize their encounter with antigen-loaded dendritic cells.
      Recent advances in 3D lymph node imaging and tissue reconstruction along with
      methods for the detection of chemokine expression and gradients have highlighted
      how T cells position themselves during activation and memory responses. This
      article covers new insights into the guidance mechanisms that co-ordinate T-cell
      responses within draining lymph nodes. Furthering our understanding of how these
      pathways are regulated and promoted will lead to the exploitation of T-cell
      positioning to further strategize vaccine design. 

PMID- 25753268
TI  - A discrete population of IFN lambda-expressing BDCA3hi dendritic cells is present
      in human thymus.
AB  - Human thymus contains two major subpopulations of dendritic cells (DCs),
      conventional DCs (cDCs) and plasmacytoid DCs (pDCs), which are mainly involved in
      central tolerance and also in protecting the thymus against infections. In blood
      and peripheral organs cDCs include the subpopulation of BDCA3(hi) DCs, considered
      as equivalents to mouse CD8alpha(+) DCs. In this study we describe in human
      thymus the presence of a discrete population of BDCA3(hi) DCs that, like their
      peripheral counterparts, express CD13, low-intermediate levels of CD11c, CLEC9A,
      high levels of XCR1, IRF8 and TLR3, and mostly lack the expression of CD11b, CD14
      and TLR7. Thymic BDCA3(hi) DCs display immature features with a low expression of
      costimulatory molecules and HLA-DR, and a low allostimulatory capacity. Also,
      BDCA3(hi) DCs exhibit a strong response to TLR3 stimulation, producing high
      levels of interferon (IFN)-lambda1 and CXCL10, which indicates that, similarly to
      thymic pDCs, BDCA3(hi) DCs can have an important role in thymus protection
      against viral infections. 

PMID- 25753269
TI  - Stressed mitochondria sound the alarm.

PMID- 25753270
TI  - GM-CSF and uPA are required for Porphyromonas gingivalis-induced alveolar bone
      loss in a mouse periodontitis model.
AB  - Granulocyte-macrophage colony-stimulating factor (GM-CSF) and urokinase-type
      plasminogen activator (uPA) can contribute to the progression of chronic
      inflammatory diseases with possible involvement of macrophages. In this study, we
      investigated the role of both GM-CSF and uPA in Porphyromonas gingivalis-induced
      experimental periodontitis using GM-CSF-/- and uPA-/- mice. Intra-oral
      inoculation of wild-type (WT) C57BL/6 mice with P. gingivalis resulted in
      establishment of the pathogen in plaque and a significant increase in alveolar
      bone resorption. The infected mice also exhibited a CD11b(+) CD86(+) macrophage
      infiltrate into the gingival tissue, as well as P. gingivalis-specific pro
      inflammatory cytokine and predominantly IgG2b antibody responses. In comparison,
      intra-oral inoculation of P. gingivalis did not induce bone resorption and there
      was significantly less P. gingivalis recovered from plaque in GM-CSF-/- and uPA-/
      mice. Furthermore, P. gingivalis did not induce a macrophage gingival infiltrate
      or activate isolated peritoneal macrophages from the gene-deficient mice. Pro
      inflammatory P. gingivalis-specific T-cell cytokine responses and serum
      interferon-gamma (IFN-gamma) and IgG2b concentrations were significantly lower in
      GM-CSF-/- mice. In uPA-/- mice, T-cell responses were lower but serum IFN-gamma
      and IgG2b levels were comparable with WT mice levels. These results suggest that
      GM-CSF and uPA are both involved in the progression of experimental
      periodontitis, possibly via a macrophage-dependent mechanism(s). 

PMID- 25753271
TI  - The activin A antagonist follistatin inhibits cystic fibrosis-like lung
      inflammation and pathology.
AB  - Cystic fibrosis (CF) is the most common life-limiting genetically acquired
      respiratory disorder. Patients with CF have thick mucus obstructing the airways
      leading to recurrent infections, bronchiectasis and neutrophilic airway
      inflammation culminating in deteriorating lung function. Current management
      targets airway infection and mucus clearance, but despite recent advances in
      care, life expectancy is still only 40 years. We investigated whether activin A
      is elevated in CF lung disease and whether inhibiting activin A with its natural
      antagonist follistatin retards lung disease progression. We measured serum
      activin A levels, lung function and nutritional status in CF patients. We studied
      the effect of activin A on CF lung pathogenesis by treating newborn CF transgenic
      mice (beta-ENaC) intranasally with the natural activin A antagonist follistatin.
      Activin A levels were elevated in the serum of adult CF patients, and correlated
      inversely with lung function and body mass index. Follistatin treatment of
      newborn beta-ENaC mice, noted for respiratory pathology mimicking human CF,
      decreased the airway activin A levels and key features of CF lung disease
      including mucus hypersecretion, airway neutrophilia and levels of mediators that
      regulate inflammation and chemotaxis. Follistatin treatment also increased body
      weight and survival of beta-ENaC mice, with no evidence of local or systemic
      toxicity. Our findings demonstrate that activin A levels are elevated in CF and
      provide proof-of-concept for the use of the activin A antagonist, follistatin, as
      a therapeutic in the long-term management of lung disease in CF patients. 

PMID- 25753273
TI  - Donors define whether CD19(+)CD27(+) tonsillar B cells are mostly memory or
      germinal-center B cells.

PMID- 25753274
TI  - [Vitamin D deficiency rickets complicating Dorfman-Chanarin syndrome].
AB  - Vitamin D deficiency rickets remains a public health issue in many parts of the
      world. In France, this diagnosis has almost disappeared since 1992 with routine
      vitamin D supplementation for children. Therefore, it is more difficult for
      doctors to identify risk factors and early signs of this disease. In this
      article, we report a rickets diagnosis acquired by vitamin D deficiency in a
      child who presented with the onset of a genu valgum and difficulty walking at the
      age of 91/2 years. This patient was a Comorian child followed up from his birth
      for Dorfman-Chanarin syndrome. Dorfman-Chanarin syndrome is a rare disease, with
      about 80 cases reported in the literature. It belongs to the group of neutral
      lipid storage diseases (NLSD) characterized especially on the skin by ichthyosis.
      This child presented risk factors for vitamin D deficiency (dark skin color,
      prolonged and exclusive breastfeeding, premature end of supplementation, and
      particularly severe ichthyosis) that should have alerted us to the risk of
      vitamin D deficiency and the need for supplementation. This case highlights the
      importance of vitamin D, especially if there are risk factors such as ichthyosis,
      and the need to remain watchful in monitoring all chronic diseases. 

PMID- 25753272
TI  - Inflammation-induced foam cell formation in chronic inflammatory disease.
AB  - Atherosclerosis is the leading cause of cardiovascular disease and is both a
      metabolic and inflammatory disease. Two models describe early events initiating
      atherosclerotic plaque formation, whereby foam cells form in response to
      hyperlipidaemia or inflammation-associated stimuli. Although these models are
      inextricably linked and not mutually exclusive, identifying the unique
      contribution of each in different disease settings remains an important question.
      Circulating monocytes are key mediators of atherogenesis in both models as
      precursors to lipid-laden foam cells formed in response to either excess lipid
      deposition in arteries, signalling via pattern-associated molecular patterns or a
      combination of the two. In this review, we assess the role of monocytes in each
      model and discuss how key steps in atherogenesis may be targeted to enhance
      clinical outcomes in patients with chronic inflammatory disease. 

PMID- 25753275
TI  - [Propranolol in infantile hemangiomas].
AB  - Propranolol has been recently approved by health authorities to treat infantile
      haemangiomas (IH). Propranolol is indicated in infants less than 5months of age
      with an IH requiring systemic therapy: IH at life-threatening and/or functional
      risk, painful ulcerated IH and IH that may cause permanent disfigurement.
      Propranolol should be initiated by physicians who have expertise in the
      diagnosis, treatment and management of IH. In addition, the first intake and
      every escalation should be administrated in a controlled clinical setting where
      adequate facilities for handling of adverse reactions, including those requiring
      urgent measures, are available. Then a monthly monitoring with dose adjustment
      weight is mandatory by the family doctor. Parents should be informed of the risk
      of hypoglycaemia and bronchoconstriction, especially during respiratory
      infectious outbreaks. The recommended duration of treatment is 6months without
      tapering. Relapses are possible necessitating a second course of 3 to 6months of
      treatment. 

PMID- 25753276
TI  - Bartonella henselae infection-associated vasculitis and crescentic
      glomerulonephritis leading to renal allograft loss.
AB  - Bartonella henselae (BH) is the main cause of cat scratch disease (CSD), which
      more typically presents as a self-limited localized suppurative lymphadenopathy
      in immunocompetent individuals. In contrast, immunocompromised patients commonly
      have systemic disease with life-threatening complications. In addition to the
      angioproliferative lesions, such as bacillary angiomatosis, an increasing number
      of immune post-infectious complications are being recognized with BH infections,
      including glomerulonephritis, vasculitis, hemophagocytic syndrome, and
      neurological problems. We report the case of a renal transplant recipient who
      developed CSD in the second year post transplantation. In addition to prolonged
      fever and generalized lymphadenopathy and splenomegaly requiring differentiation
      from a post-transplant lymphoproliferative disorder, the course was complicated
      by the development of dermal leukocytoclastic vasculitis and pauci-immune
      necrotizing and crescentic glomerulonephritis, which led to failure of the renal
      graft. Glomerulonephritis as a complication of CSD has never been described in a
      kidney allograft, to our knowledge. Awareness of the diverse clinical symptoms
      associated with BH, including granulomatous/suppurative lesions and other less
      common complications can lead to more rapid and accurate diagnosis. Also, as
      recommended by the current guidelines, a thorough history of pet ownership should
      be part of the clinical evaluation before and after transplantation for all
      transplant recipients.

PMID- 25753277
TI  - Socio-economic patterning in adulthood and depressive symptoms among a community
      sample of older adults in the United States.

PMID- 25753278
TI  - Risk factors associated with mortality from breast cancer in Waikato, New
      Zealand: a case-control study.
AB  - OBJECTIVES: The aim of this study is to identify key characteristics associated
      with mortality from breast cancer among women with newly diagnosed breast cancer
      in New Zealand (NZ). STUDY DESIGN: Case-control study. METHODS: All primary
      breast cancers diagnosed between 01/01/2002 and 31/12/2010 in Waikato, NZ, were
      identified from the Waikato Breast Cancer Register. A total of 258 breast cancer
      deaths were identified from 1767 invasive cancers diagnosed over this period.
      RESULTS: Breast cancer deaths (n = 246) were compared with an age and year of
      diagnosis matched control group (n = 652) who were alive at the time of the death
      of the corresponding case and subsequently did not die from breast cancer.
      Diagnosis through symptomatic presentation, advanced stage, higher grade, absent
      hormone receptors (i.e. oestrogen and progesterone) and HER-2 amplification were
      associated with significantly higher risks of breast cancer mortality in
      bivariate analysis. Tumour stage, grade and hormone receptor status remained
      significant in the multivariable model, while mode of detection and HER-2 status
      were non-significant. In the bivariate analysis, Maori women had a higher risk of
      breast cancer mortality compared to NZ European women (OR 1.34) which was
      statistically non-significant. However in the adjusted model, risk of mortality
      was lower for Maori compared to NZ European women, although this was not
      significant statistically (OR 0.85). CONCLUSIONS: Mortality pattern from breast
      cancer in this study were associated with established risk factors. Ethnic
      inequity in breast cancer mortality in NZ appears to be largely attributable to
      delay in diagnosis and tumour related factors. Further research in a larger
      cohort is needed to identify the full impact of these factors on ethnic inequity
      in breast cancer mortality.

PMID- 25753279
TI  - Food reformulation and the (neo)-liberal state: new strategies for strengthening
      voluntary salt reduction programs in the UK and USA.
AB  - Globally, excess salt intake is a significant cause of preventable heart disease
      and stroke, given the established links between high salt intake, high blood
      pressure, and cardiovascular disease. This paper describes and evaluates the
      voluntary approaches to salt reduction that operate in the United Kingdom and the
      United States, and proposes a new strategy for improving their performance.
      Drawing on developments in the theory and practice of public health governance,
      as well as theoretical ideas theoretical ideas from the field of regulatory
      studies, this paper proposes a responsive regulatory model for managing food
      reformulation initiatives, including salt reduction programs. This model provides
      a transparent framework for guiding industry behavior, making full use of
      industry's willingness to participate in efforts to create healthier products,
      but using 'legislative scaffolding' to escalate from self-regulation towards co
      regulation if industry fails to play its part in achieving national goals and
      targets. 

PMID- 25753280
TI  - Towards universal health coverage in India: a historical examination of the
      genesis of Rashtriya Swasthya Bima Yojana - The health insurance scheme for low
      income groups.
AB  - OBJECTIVES: Many low- and middle-income countries have introduced State-funded
      health programmes for vulnerable groups as part of global efforts to universalise
      health coverage. Similarly, India introduced the Rashtriya Swasthya Bima Yojana
      (RSBY) in 2008, a publicly-funded national health insurance scheme for people
      below the poverty line. The authors explore the RSBY's genesis and early
      development in order to understand its conceptualisation and design principles
      and thereby establish a baseline for assessing RSBY's performance in the future.
      STUDY DESIGN: Qualitative case study of the RSBY in Delhi. METHODS: This paper
      presents results from documentary analysis and semi-structured interviews with
      senior-level policymakers including the former Labour Minister, central
      government officials and affiliates, and technical specialists from the World
      Bank and GIZ. RESULTS: With national priorities focused on broader economic
      development goals, the RSBY was conceptualised as a social investment in worker
      productivity and future economic growth in India. Hence, efficiency, competition,
      and individual choice rather than human needs or egalitarian access were
      overriding concerns for RSBY designers. This measured approach was strongly
      reflected in RSBY's financing and benefit structure. Hence, the programme's focus
      on only the 'poorest' (BPL) among the poor. Similarly, only costlier forms of
      care, secondary treatments in hospitals, which policymakers felt were more likely
      to have catastrophic financial consequences for users were covered. CONCLUSIONS:
      This paper highlights the risks of a narrow approach driven by developmental
      considerations alone. Expanding access and improving financial protection in
      India and elsewhere requires a more balanced approach and evidence-informed
      health policies that are guided by local morbidity and health spending patterns.

PMID- 25753281
TI  - Quantile regression analyses of associated factors for body mass index in Korean
      adolescents.
AB  - OBJECTIVES: This study examined the influence of home and school environments,
      and individual health-risk behaviours on body weight outcomes in Korean
      adolescents. STUDY DESIGN: This was a cross-sectional observational study.
      METHODS: Quantile regression models to explore heterogeneity in the association
      of specific factors with body mass index (BMI) over the entire conditional BMI
      distribution was used. A nationally representative web-based survey for youths
      was used. RESULTS: Paternal education level of college or more education was
      associated with lower BMI for girls, whereas college or more education of mothers
      was associated with higher BMI for boys; for both, the magnitude of association
      became larger at the upper quantiles of the conditional BMI distribution. Girls
      with good family economic status were more likely to have higher BMIs than those
      with average family economic status, particularly at the upper quantile of the
      conditional BMI distribution. Attending a co-ed school was associated with lower
      BMI for both genders with a larger association at the upper quantiles.
      Substantial screen time for TV watching, video games, or internet surfing was
      associated with a higher BMI with a larger association at the upper quantiles for
      both girls and boys. Dental prevention was negatively associated with BMI,
      whereas suicide consideration was positively associated with BMIs of both genders
      with a larger association at a higher quantile. CONCLUSIONS: These findings
      suggest that interventions aimed at behavioural changes and positive parental
      roles are needed to effectively address high adolescent BMI.

PMID- 25753282
TI  - Factors affecting ambulance utilization for asthma attack treatment:
      understanding where to target interventions.
AB  - OBJECTIVES: Asthma is a serious, sometimes fatal condition, in which attacks vary
      in severity, potentially requiring emergency medical services (EMS) ambulance
      treatment. A portion of asthma attacks requiring EMS ambulance treatment may be
      prevented with improved education and access to care. The aim of this study was
      to identify areas of the city with high rates of utilization of EMS ambulance for
      treatment, and the demographics, socio-economic status, and time of day
      associated with these rates, to better target future interventions to prevent
      emergencies and reduce cost. STUDY DESIGN: A cross-sectional study was conducted
      on individuals in Houston, TX (USA) requiring ambulance treatment for asthma
      attacks from 2004 to 2011. METHODS: 12,155 EMS ambulance-treated asthma attack
      cases were linked to census tracts. High rate treatment areas were identified
      with geospatial mapping. Census tract demographic characteristics of these high
      rate areas were compared with the remainder of the city using logistic
      regression. The association between case level demographics and the time of day
      of asthma attack within the high rate area was also assessed with logistic
      regression. RESULTS: EMS ambulance-treated high rate areas were identified and
      found to have a utilization incidence rate over six times higher per 100,000
      people than the remainder of the city. There is an increased risk of location in
      this high rate area with a census tract level increase of percent of population:
      earning less than $10,000 yearly income (RR 1.21, 1.16-1.26), which is black (RR
      1.08, 1.07-1.10), which is female (RR 1.34, 1.20-1.49) and have obtained less
      than a high school degree (RR 1.02, 1.01-1.03). Within the high rate area, case
      level data indicates an increased risk of requiring an ambulance after normal
      doctor office hours for men compared with women (RR 1.13, 1.03-1.22), for black
      compared with Hispanic ethnicity (RR 1.31, 1.08-1.59), or for adults (less than
      41 and greater than 60) compared with children. CONCLUSIONS: Interventions to
      prevent asthma emergencies should be targeted in the high rate area and towards
      groups identified most at risk. Consideration should be given to improved access
      to care after normal doctor office hours in these locations. While ambulance
      treatment reflects the most urgent care needs, these interventions are also
      expected to reduce the need for emergency room visits.

PMID- 25753283
TI  - Prenatal detection of congenital heart disease: the case for improved training.

PMID- 25753284
TI  - Seeking and receiving social support on Facebook for surgery.
AB  - Social networking sites such as Facebook provide a new way to seek and receive
      social support, a factor widely recognized as important for one's health.
      However, few studies have used actual conversations from social networking sites
      to study social support for health related matters. We studied 3,899 Facebook
      users, among a sample of 33,326 monitored adults, who initiated a conversation
      that referred to surgery on their Facebook Wall during a six-month period. We
      explored predictors of social support as measured by number of response posts
      from "friends." Among our sample, we identified 8,343 Facebook conversation
      threads with the term "surgery" in the initial post with, on average, 5.7
      response posts (SD 6.2). We used a variant of latent semantic analysis to explore
      the relationship between specific words in the posts that allowed us to develop
      three thematic categories of words related to family, immediacy of the surgery,
      and prayer. We used generalized linear mixed models to examine the association
      between characteristics of the Facebook user as well as the thematic categories
      on the likelihood of receiving response posts following the announcement of a
      surgery. Words from the three thematic categories were used in 32.5% (family),
      39.5 (immediacy), and 50.7% (prayer) of root posts. Few user characteristics were
      associated with response in multivariate models [rate ratios, RR, 1.08 (95% CI
      1.01, 1.15) for married/living with partner; 1.10 (95% CI 1.03, 1.19) for annual
      income > $75,000]. In multivariate models adjusted for Facebook user
      characteristics and network size, use of family and prayer words in the root post
      were associated with significantly higher number of response posts, RR 1.40 (95%
      CI 1.37, 1.43) and 2.07 (95% CI 2.02, 2.12) respectively. We found some evidence
      of social support on Facebook for surgery and that the language used in the root
      post of a conversation thread is predictive of overall response. 

PMID- 25753286
TI  - The mediating effect of effort-reward imbalance in household and family work on
      the relationship between education and women's health.
AB  - Occupational stress as a key determinant for explaining health inequalities has
      been well established while the impact of stress related to family work has
      rarely been considered. This study investigates whether stress in household and
      family work may contribute to health inequalities in women. We used a population
      based sample of German mothers (n = 3129) to determine the total, direct and
      indirect effects of education on somatic complaints by means of OLS regression
      based mediation models. Inference about indirect effects was determined by 95%
      bias corrected bootstrap confidence intervals. Education was assessed by a
      measure combining school education and vocational training. Stress was measured
      using the adopted effort-reward-imbalance (ERI) questionnaire for household and
      family work. The von Zerssen list of somatic complaints was used as measure of
      subjective health. We found a significant total effect of education on somatic
      complaints (p <= 0.001) as well as significant indirect effects through 'effort'
      (p = 0.006) and 'reward' in household and family work (p <= 0.001). However, the
      subscales of ERI pointed into different directions: while levels of 'effort'
      increased with women's educational attainment, levels of distress related to low
      'reward' decreased with higher levels of education. Our findings suggest that the
      effect of women's education on somatic complaints is mediated through stress
      related to low reward for household and family work. In particular, lack of
      'societal esteem' for household and family work contributed to health
      disadvantages in lower educated mothers. We conclude that research on health
      inequality would benefit from taking stressful experiences in household and
      family work greater into account. 

PMID- 25753285
TI  - Adverse childhood experiences and intimate partner aggression in the US: sex
      differences and similarities in psychosocial mediation.
AB  - Six in ten people in the general population have been exposed to adverse
      childhood experiences (ACEs). Intimate partner violence (IPV) is a major public
      health problem in the US. The main objective of this study was to assess sex
      differences in the role of posttraumatic stress disorder (PTSD), substance abuse,
      and depression as mediators in the association between ACEs and intimate partner
      aggression. Data were obtained from Wave 2 (2004-2005) of the National
      Epidemiologic Survey on Alcohol and Related Conditions. Structural equation
      modeling was used to determine the mediational role of PTSD, substance abuse and
      depression in the association between ACE constructs (neglect,
      physical/psychological abuse, sexual abuse, parental violence, and parental
      incarceration/psychopathology) and intimate partner aggression. Among men, PTSD
      mediated the relationship between sexual abuse and intimate partner aggression.
      However, among men and women, substance abuse mediated the relationship between
      physical and psychological abuse and intimate partner aggression. IPV programs
      geared towards aggressors should address abuse (sexual, physical and
      psychological), which occurred during childhood and recent substance abuse and
      PTSD. These programs should be implemented for men and women. Programs aimed at
      preventing abuse of children may help to reduce rates of depression and PTSD in
      adulthood, and subsequent intimate partner aggression. 

PMID- 25753287
TI  - The stories we tell: qualitative research interviews, talking technologies and
      the 'normalisation' of life with HIV.
AB  - Since the earliest days of the HIV/AIDS epidemic, talking about the virus has
      been a key way affected communities have challenged the fear and discrimination
      directed against them and pressed for urgent medical and political attention.
      Today, HIV/AIDS is one of the most prolifically and intimately documented of all
      health conditions, with entrenched infrastructures, practices and technologies-
      what Vinh-Kim Nguyen has dubbed 'confessional technologies'--aimed at encouraging
      those affected to share their experiences. Among these technologies, we argue, is
      the semi-structured interview: the principal methodology used in qualitative
      social science research focused on patient experiences. Taking the performative
      nature of the research interview as a talking technology seriously has
      epistemological implications not merely for how we interpret interview data, but
      also for how we understand the role of research interviews in the enactment of
      'life with HIV'. This paper focuses on one crucial aspect of this enactment: the
      contemporary 'normalisation' of HIV as 'just another' chronic condition--a
      process taking place at the level of individual subjectivities, social
      identities, clinical practices and global health policy, and of which social
      science research is a vital part. Through an analysis of 76 interviews conducted
      in London (2009-10), we examine tensions in the experiential narratives of
      individuals living with HIV in which life with the virus is framed as 'normal',
      yet where this 'normality' is beset with contradictions and ambiguities. Rather
      than viewing these as a reflection of resistances to or failures of the enactment
      of HIV as 'normal', we argue that, insofar as these contradictions are generated
      by the research interview as a distinct 'talking technology', they emerge as
      crucial to the normative (re)production of what counts as 'living with HIV' (in
      the UK) and are an inherent part of the broader performative 'normalisation' of
      the virus.

PMID- 25753289
TI  - Patterns of use and outcome of inferior vena cava filters in a tertiary care
      setting.
AB  - BACKGROUND: Inferior vena cava (IVC) filter placement is increasing although the
      evidence to justify their use is limited. Many filters are left in place
      indefinitely, thereby exposing patients to long-term complications. OBJECTIVES:
      To review indications, complications, and follow-up data of patients undergoing
      IVC filter placement at our center. METHODS: A retrospective review of
      consecutive admitted patients who underwent IVC filter insertion in a large
      university hospital with a level I trauma center. Thrombosis specialists
      retrospectively assessed the appropriateness of indication for IVC filter
      placement as well as referral for retrieval. RESULTS: Overall, 405 filters were
      inserted between 2009 and 2013. All filters were retrievable. IVC filter was
      placed as a primary prevention in 42% of patients. Fifty-two patients (12.8%)
      experienced at least one filter-related complication. The most common
      complication was deep vein thrombosis occurring in 6.9% of cases. Almost a third
      of all complications occurred in filters originally placed for prophylactic
      indications. Only 13.6% of filters were successfully removed. Nevertheless,
      according to our reviewers, an attempt for filter retrieval should have been made
      in 57% of all cases and in 86% of trauma patients. A significantly higher
      retrieval rate was found in patients followed at our thrombosis clinic (P <
      0.01). During follow-up, 95 patients (23.4%) died, most of them with active
      cancer. CONCLUSIONS: IVC filters are placed in many cases for prophylactic
      indications. Their low retrieval rates together with relatively high risk of long
      term complications, questions their extensive utilization. Prospective trials
      addressing the safety and efficacy of IVC filters are still warranted.

PMID- 25753288
TI  - PI3kalpha and STAT1 Interplay Regulates Human Mesenchymal Stem Cell Immune
      Polarization.
AB  - The immunomodulatory capacity of mesenchymal stem cells (MSCs) is critical for
      their use in therapeutic applications. MSC response to specific inflammatory cues
      allows them to switch between a proinflammatory (MSC1) or anti-inflammatory
      (MSC2) phenotype. Regulatory mechanisms controlling this switch remain to be
      defined. One characteristic feature of MSC2 is their ability to respond to
      IFNgamma with induction of indoleamine 2,3-dioxygenase (IDO), representing the
      key immunoregulatory molecule released by human MSC. Here, we show that STAT1 and
      PI3Kalpha pathways interplay regulates IFNgamma-induced IDO production in MSC.
      Chemical phosphoinositide 3-kinase (PI3K) pan-inhibition, PI3Kalpha-specific
      inhibition or shRNA knockdown diminished IFNgamma-induced IDO production. This
      effect involved PI3Kalpha-mediated upregulation of STAT1 protein levels and
      phosphorylation at Ser727. Overexpression of STAT1 or of a constitutively active
      PI3Kalpha mutant failed to induce basal IDO production, but shifted MSC into an
      MSC2-like phenotype by strongly enhancing IDO production in response to IFNgamma
      as compared to controls. STAT1 overexpression strongly enhanced MSC-mediated T
      cell suppression. The same effect could be induced using short-term pretreatment
      of MSC with a chemical inhibitor of the counter player of PI3K, phosphatase and
      tensin homolog. Finally, downregulation of STAT1 abrogated the immunosuppressive
      capacity of MSC. Our results for the first time identify critical upstream
      signals for the induced production of IDO in MSCs that could be manipulated
      therapeutically to enhance their immunosuppressive phenotype.

PMID- 25753290
TI  - Education on prescribing for older patients in the Netherlands: a curriculum
      mapping.
AB  - PURPOSE: Pharmacology and pharmacotherapy education is being increasingly
      integrated in medical curricula, which might lead to a specific loss of knowledge
      in these subjects. This, in turn, could lead to harmful prescribing errors,
      especially in vulnerable older patients. METHODS: Teachers who coordinated
      education in Dutch medical schools completed a structured interview on
      (geriatric) pharmacology and pharmacotherapy education. A list of core learning
      goals was developed. Pharmacology and pharmacotherapy education in general was
      compared to geriatric pharmacology and pharmacotherapy education. RESULTS: All
      Dutch medical schools participated. Contact hours for education in pharmacology
      and pharmacotherapy ranged from 39 to 107 h; ECTSs (representing 28 study hours)
      ranged from 0 to 3. The various curricula covered, on average, 79% of all
      learning goals for these subjects: knowledge 85%, skills 76%, and attitudes 66%;
      the curricula also covered specific geriatric goals: knowledge 87% and skills
      65%. All geriatric learning goals were met if a geriatrician was among the
      coordinators. Half (4 of 8) of the medical schools lacked appropriate assessment
      procedures. Evaluation was mostly based on students' opinions. Teachers rated
      students as being moderately well prepared for daily practice. CONCLUSIONS: There
      are large differences in the quantity and quality of (geriatric) pharmacology and
      pharmacotherapy education in Dutch medical schools. In general, more time should
      be devoted to skills and attitude, and the assessment procedures should be
      optimized with high priority. Other curricula with a problem-based approach might
      benefit from the points of improvement described in this article.

PMID- 25753291
TI  - Meta-analysis of the risks of hypertension and QTc prolongation in patients with
      advanced non-small cell lung cancer who were receiving vandetanib.
AB  - BACKGROUND: A meta-analysis of published data was conducted to investigate the
      overall risks of hypertension and QTc prolongation in patients with advanced non
      small cell lung cancer (NSCLC) who were receiving vandetanib. METHODS: A
      computerized search through electronic databases, including PubMed and Embase
      (until Dec 2014), was performed to obtain eligible randomized controlled trials
      (RCTs) that compared hypertension and/or QTc prolongation profile of vandetanib
      alone or plus chemotherapy with control groups (placebo, single targeted therapy,
      chemotherapy, or a combination of them) in patients with advanced NSCLC. The
      outcome measures were the overall risks of hypertension and QTc prolongation.
      Relative risk (RR) and 95% confidence interval (CI) were calculated and pooled
      using a random effects model. RESULTS: A total of nine RCTs, which involved 4813
      patients, were enrolled in the present study. A significant increase in risk was
      observed for all-grade hypertension (RR 5.58; 95% CI 4.16 to 7.48; P < 0.00001)
      and grade >=3 hypertension (RR 4.79; 95% CI 2.31 to 9.93; P < 0.0001) in advanced
      NSCLC patients who were receiving vandetanib compared with the controls.
      Moreover, vandetanib significantly prolonged all-grade QTc interval (RR 7.90; 95%
      CI 4.03 to 15.50; P < 0.00001) and grade >=3 QTc interval (RR 3.12; 95% CI 1.01
      to 9.63; P = 0.05). CONCLUSIONS: Current evidence showed that significant risks
      in developing hypertension and QTc prolongation exist in advanced NSCLC patients
      who were receiving vandetanib. Thus, appropriate monitoring and management of
      these events are recommended.

PMID- 25753292
TI  - The use of 30 degrees  test in nontrauma patients suspected of elevated
      intracranial pressure.

PMID- 25753293
TI  - Relationship between duration of prehospital resuscitation and favorable
      prognosis in ventricular fibrillation.
AB  - OBJECTIVE: There appears to be an optimal point in balancing the relative
      benefits of extending the resuscitation time to obtain return of spontaneous
      circulation in the prehospital setting and the initiation of therapies such as
      extracorporeal cardiopulmonary resuscitation (CPR). This study investigated how
      prehospital CPR duration is related to survival and neurologic outcome in
      ventricular fibrillation (VF) and tried to find the tolerable time for
      prehospital resuscitation. MATERIALS AND METHODS: Out-of-hospital cardiac arrest
      patients with VF in Funabashi City, Japan, from January 2009 to December 2013
      were reviewed. Resuscitation teams that included physicians were dispatched to
      incident sites. Survival rate at 24 hours and neurologic outcome at 30 days were
      analyzed with respect to prehospital CPR duration. RESULTS: A total of 172
      patients were evaluated. Seventy-three patients were alive at 24 hours. Thirty
      four patients had favorable neurologic outcomes after 30 days. Of the 69 patients
      who required prolonged prehospital CPR (>30 minutes), 6 were alive at 24 hours,
      and only 1 had a favorable neurologic outcome at 30 days. Logistic regression
      model showed that both survival rate at 24 hours and neurologic outcome at 30
      days deteriorated with the increase in prehospital CPR duration (both P < .001).
      CONCLUSION: The prognosis of out-of-hospital cardiac arrest patients with VF
      deteriorated with the increase in prehospital CPR duration. Favorable results are
      less likely especially in cases of prolonged prehospital CPR (>30 minutes).
      Therefore, it may be necessary to consider transportation to a more definitive
      treatment facility rather than extending conventional CPR in the prehospital
      setting.

PMID- 25753295
TI  - Consequences of contextual factors on clinical reasoning in resident physicians.
AB  - Context specificity and the impact that contextual factors have on the complex
      process of clinical reasoning is poorly understood. Using situated cognition as
      the theoretical framework, our aim was to evaluate the verbalized clinical
      reasoning processes of resident physicians in order to describe what impact the
      presence of contextual factors have on their clinical reasoning. Participants
      viewed three video recorded clinical encounters portraying straightforward
      diagnoses in internal medicine with select patient contextual factors modified.
      After watching each video recording, participants completed a think-aloud
      protocol. Transcripts from the think-aloud protocols were analyzed using a
      constant comparative approach. After iterative coding, utterances were analyzed
      for emergent themes with utterances grouped into categories, themes and
      subthemes. Ten residents participated in the study with saturation reached during
      analysis. Participants universally acknowledged the presence of contextual
      factors in the video recordings. Four categories emerged as a consequence of the
      contextual factors: (1) emotional reactions (2) behavioral inferences (3)
      optimizing the doctor patient relationship and (4) difficulty with closure of the
      clinical encounter. The presence of contextual factors may impact clinical
      reasoning performance in resident physicians. When confronted with the presence
      of contextual factors in a clinical scenario, residents experienced difficulty
      with closure of the encounter, exhibited as diagnostic uncertainty. This finding
      raises important questions about the relationship between contextual factors and
      clinical reasoning activities and how this relationship might influence the cost
      effectiveness of care. This study also provides insight into how the phenomena of
      context specificity may be explained using situated cognition theory. 

PMID- 25753294
TI  - Gestational weight gain and obesity, adiposity and body size in African-American
      and Dominican children in the Bronx and Northern Manhattan.
AB  - Gestational weight gain (GWG) is potentially modifiable and is associated with
      infant size and body composition; however, long-term effects on childhood obesity
      have not been reported among multi-ethnic urban populations. We examined the
      association between GWG and child anthropometric measures and body composition at
      7 years [waist circumference (WC), body mass index z-score (BMIZ), obesity (BMIZ
      >=95%ile) and bioelectrical impedance analysis estimates of percentage body fat
      (%fat)] in African-American and Dominican dyads (n = 323) in the Columbia Center
      for Children's Environmental Health prospective birth cohort study from 1998 to
      2013. Linear and logistic regression evaluated associations between excessive GWG
      [>Institute of Medicine (IOM) 2009 guidelines] and outcomes, adjusting for pre
      pregnancy BMI and covariates. Pre-pregnancy BMI (mean +/- standard deviation, all
      such values) and total GWG were 25.8 +/- 6.2 kg m(-2) (45% overweight/obese) and
      16.4 +/- 7.9 kg (64% > IOM guidelines), respectively. Excessive GWG was
      associated with higher BMIZ {0.44 [95% confidence interval (CI): 0.2, 0.7], P <
      0.001}, WC [beta: 2.9 cm (95% CI: 1.1, 4.6), P = 0.002], %fat at 7 years [beta:
      2.2% (95% CI: 1.0, 3.5), P = 0.001)] and obesity [odds ratio: 2.93 (95% CI: 1.5,
      5.8), P = 0.002]. Pre-pregnancy BMI was positively associated with child size,
      adiposity and obesity (all P < 0.05). Excessive GWG was highly prevalent and was
      associated with child obesity, greater percentage body fat and abdominal
      adiposity. Strategies to support healthy GWG are warranted to promote healthy
      growth and prevent childhood obesity.

PMID- 25753297
TI  - Comparison of reducing epicardial fat by exercise, diet or bariatric surgery
      weight loss strategies: a systematic review and meta-analysis.
AB  - The objectives were to determine whether epicardial fat (EAT) is subject to
      modification, and whether various strategies accomplish this end point and the
      relationship between weight loss and EAT. A systematic review of the literature
      following meta-analysis guidelines was conducted using the search strategy
      'epicardial fat' OR 'epicardial adipose tissue' AND 'diet' OR 'exercise' OR
      'bariatric surgery (BS)' OR 'change in body weight' limited to humans. Eleven
      articles were identified with 12 intervention approaches of which eight studies
      showed a statistically significant reduction in EAT. A random-effects meta
      analysis suggests an overall significant reduction of 1.12 standardized units
      (95% CI = [-1.71, -0.54], P value < 0.01). While there is a large amount of
      heterogeneity across study groups, a substantial amount of this variability can
      be accounted for by considering intervention type and change in body mass index
      (BMI). These variables were incorporated into a random-effects meta-regression
      model. Using this analysis, significant EAT reduction occurred with diet and BS
      but not with exercise. BMI reductions correlated significantly with EAT
      reductions for diet-based interventions, i.e. for some but not all interventions.
      In conclusion, EAT, a factor that is significantly associated with coronary
      artery disease, can be modified. The type of intervention, in addition to the
      amount of weight loss achieved, is predictive of the amount of EAT reduction. 

PMID- 25753296
TI  - Systematic identification and characterization of long intergenic non-coding RNAs
      in fetal porcine skeletal muscle development.
AB  - Long intergenic non-coding RNAs (lincRNAs) play important roles in many cellular
      processes. Here, we present the first systematic identification and
      characterization of lincRNAs in fetal porcine skeletal muscle. We obtained a
      total of 55.02 million 90-bp paired-end reads and assembled 54,550 transcripts
      using cufflinks. We developed a pipeline to identify 570 multi-exon lincRNAs by
      integrating a set of previous approaches. These putative porcine lincRNAs share
      many characteristics with mammalian lincRNAs, such as a relatively short length,
      small number of exons and low level of sequence conservation. We found that the
      porcine lincRNAs were preferentially located near genes mediating transcriptional
      regulation rather than those with developmental functions. We further
      experimentally analyzed the features of a conserved mouse lincRNA gene and found
      that isoforms 1 and 4 of this lincRNA were enriched in the cell nucleus and were
      associated with polycomb repressive complex 2 (PRC2). Our results provide a
      catalog of fetal porcine lincRNAs for further experimental investigation of the
      functions of these genes in the skeletal muscle developmental process. 

PMID- 25753298
TI  - Relation of vitamin D deficiency and new-onset atrial fibrillation among
      hypertensive patients.
AB  - Vitamin D deficiency is associated with various cardiovascular disorders
      including hypertension, coronary artery disease, and heart failure. The renin
      angiotensin-aldosterone system (RAS) axis is activated in vitamin D deficiency.
      The RAS axis also plays a role in the pathophysiology of atrial fibrillation
      (AF). We aimed to investigate whether vitamin D deficiency is a risk factor for
      the development of new-onset AF in hypertension. A total of 227 hypertensive
      patients were enrolled, of whom 137 had new-onset AF; 90 patients without AF were
      included in the control group. The age of the patient, left atrial diameter, and
      vitamin D deficiency increased the probability of new-onset AF independent from
      confounding factors (odds ratio [OR], 1.04; 95% confidence interval [CI], 1.01
      1.08; P = .03 for age; OR, 1.88; 95% CI, 1.15-3.45; P = .03 for left atrial
      diameter; OR, 1.68; 95% CI, 1.18-2.64; P = .03 for vitamin D deficiency). Vitamin
      D deficiency is associated with new-onset AF in hypertension.

PMID- 25753300
TI  - Treatment: special conditions: co-existing heart disease: atrial fibrillation.

PMID- 25753299
TI  - Relationship between different blood pressure measurements and left ventricular
      mass by cardiac magnetic resonance imaging in end-stage renal disease.
AB  - Hypertension is prevalent in patients with end-stage renal disease and is
      strongly associated with left ventricular hypertrophy (LVH), an independent
      predictor of cardiovascular mortality. Blood pressure (BP) monitoring in
      hemodialysis patients may be unreliable because of its lability and variability.
      We compared different methods of BP measurement and their relationship with LVH
      on cardiac magnetic resonance imaging. Sixty patients undergoing chronic
      hemodialysis at a single dialysis center had BP recorded at each dialysis session
      over 12 weeks: pre-dialysis, initial dialysis, nadir during dialysis, and post
      dialysis. Forty-five of these patients also underwent 44-hour inter-dialytic
      ambulatory BP monitoring. Left ventricular mass index (LVMI) was measured using
      cardiac magnetic resonance imaging and the presence of LVH was ascertained.
      Receiver operator characteristic curves were generated for each BP measurement
      for predicting LVH. The mean LVMI was 68 g/m(2) (SD = 15 g/m(2)); 13/60 patients
      (22%) had LVH. Mean arterial pressure measured shortly after initiation of
      dialysis session was most strongly correlated with LVMI (Pearson correlation
      coefficient r = 0.59, P < .0001). LVH was best predicted by post-dialysis
      systolic BP (area under the curve, 0.83; 95% confidence interval, 0.72-0.94) and
      initial dialysis systolic BP (area under the curve, 0.81; 95% confidence
      interval, 0.70-0.92). Forty-four-hour ambulatory BP and BP variability did not
      significantly predict LVH. Initial dialysis mean arterial pressure and systolic
      BP and post-dialysis systolic BP are the strongest predictors of LVH, and may
      represent the potentially best treatment targets in hemodialysis patients to
      prevent end-organ damage. Further studies are needed to confirm whether treatment
      targeting these BP measurements can optimize cardiovascular outcomes.

PMID- 25753301
TI  - Direct angiotensin II type 2 receptor stimulation by compound 21 prevents
      vascular dementia.
AB  - Angiotensin II type 2 (AT(2)) receptor activation has been reported to play a
      role in cognitive function, although its detailed mechanisms and pathologic
      significance are not fully understood. We examined the possibility that direct
      AT(2) receptor stimulation by compound 21 (C21) could prevent cognitive decline
      associated with hypoperfusion in the brain.We employed a bilateral common carotid
      artery stenosis (BCAS) model in mice as a model of vascular dementia. The Morris
      water maze task was performed 6 weeks after BCAS operation. Azilsartan (0.1
      mg/kg/day) or C21 (10 MUg/kg/day) was administered from 1 week before BCAS.
      Cerebral blood flow (CBF) and inflammatory cytokine levels were also determined.
      Wild-type (WT) mice showed significant prolongation of escape latency after BCAS,
      and this cognitive impairment was attenuated by pretreatment with azilsartan.
      Cognitive impairment was more marked in AT(2) receptor knockout (AT(2)KO) mice,
      and the preventive effect of azilsartan on cognitive decline was weaker in
      AT(2)KO mice than in WT mice, suggesting that the improvement of cognitive
      decline by azilsartan may involve stimulation of the AT(2) receptor. The
      significant impairment of spatial learning after BCAS in WT mice was attenuated
      by C21 treatment. The decrease in CBF in the BCAS-treated group was blunted by
      C21 treatment, and the increase in TNF-alpha and MCP-1 mRNA expression after BCAS
      was attenuated by C21 treatment. These findings indicate that direct AT(2)
      receptor stimulation attenuates ischemic vascular dementia induced by
      hypoperfusion at least in part through an increase in CBF, and a reduction of
      inflammation.

PMID- 25753302
TI  - Decreased expression of Bauhinia purpurea lectin is a predictor of gastric cancer
      recurrence.
AB  - PURPOSE: Molecular markers as indicators for gastric cancer recurrence are
      urgently required. The aim of this study was to identify lectins that can be used
      to predict gastric cancer recurrence after gastrectomy. METHODS: We created
      lectin expression profiles by microarray analysis for 60 patients, who underwent
      surgery for gastric cancer at the Oita University Hospital between January, 2005
      and December, 2007. Lectin expression and clinicopathological factors in patients
      who suffered gastric cancer recurrence and those who did not were compared by
      univariate and multivariate analyses. RESULTS: Thirteen lectins showed a
      significant increase in binding to cancer tissues, whereas 11 lectins showed a
      significant decrease in binding to cancer tissues, when compared with binding to
      normal epithelia. Multivariate analysis revealed that lymph node metastasis and
      low Bauhinia purpurea lectin (BPL)-binding signals were independent predictive
      factors for recurrence. All patients with low BPL expression had significantly
      worse relapse-free survival than those with high BPL expression. CONCLUSIONS: Our
      results using a novel lectin microarray system provide the first solid evidence
      that BPL expression is a predictor of gastric cancer recurrence.

PMID- 25753303
TI  - Back to the past or on to the future?

PMID- 25753304
TI  - Construction of an upconversion nanoprobe with few-atom silver nanoclusters as
      the energy acceptor.
AB  - Herein we report that few-atom silver nanoclusters (Ag NCs) can be effective
      energy acceptors for upconversion phosphors (UCPs). A luminescence resonance
      energy transfer (LRET) probe for biothiols was constructed by decorating UCPs
      with dithiol-stabilized Ag NCs. Owing to the unique properties of ultrasmall NCs,
      properties which bridge the gap between those of small molecules and those of
      nanoparticles, the use of approximately 1.9 nm Ag NCs as energy acceptors endows
      the probe with high energy-transfer efficiency, good biocompatibility, and
      flexibility. The UCP-Ag NC nanoprobe enables rapid and robust target assay in
      solutions. It was also uploaded into living cells and used to detect
      intracellular biothiol levels with high discrimination. Moreover, the probe shows
      transportability in vivo and can be used for tissue imaging. The facile growth of
      few-atom metal NCs on diverse templates may enable the development of various
      nanoprobes combining UCPs and metal NCs. 

PMID- 25753306
TI  - Countrywide stroke incidence, subtypes, management and outcome in a multiethnic
      Asian population: the Singapore Stroke Registry--methodology.
AB  - RATIONALE: Because of its rapidly-growing and aging populations, the global
      burden of stroke will be felt most strongly in Asia. Data from Asia are scarce.
      Even rarer are data from multiethnic populations. AIM: The Singapore Stroke
      Registry is a countrywide registry of risk factors, stroke subtypes, management
      and outcome of incident and recurrent stroke in multiethnic Singapore. METHODS
      AND DESIGN: Using a cold-pursuit design, potential subjects are identified from
      medical claims, hospital discharge summaries and death certificates. Standardized
      methods are used for case ascertainment and data recording by trained staff into
      standardized case report forms. All ages and both genders are included. STUDY
      OUTCOME: Stroke incidence, subtypes and mortality will be calculated. Trend data
      will be obtained. Inter-ethnic differences will be explored. DISCUSSION: The
      Registry has many features of an 'ideal' incidence study. Previously unavailable
      countrywide data on an Asian population will be acquired. The unique data on
      inter-ethnic differences will help fill knowledge gaps in stroke epidemiology.

PMID- 25753307
TI  - Clonal wound re-epithelialisation after radiotherapy for skin cancer.
AB  - Simple clinical observations can give useful insights into biological processes
      in humans. Here we present a temporal series of pictures addressing the tissue
      response of a basal cell carcinoma to radiotherapy, where re-epithelialisation
      (RE) after radiotherapy appeared to occur by clonal regrowth, rather than the
      usually described sheet-like RE. 

PMID- 25753308
TI  - The impact of Chiari malformation on daily activities: A report from the national
      Conquer Chiari Patient Registry database.
AB  - BACKGROUND: Chiari malformation (CM) is characterized by herniation of the
      cerebellar tonsils into the cervical spine. While ample literature on CM exists
      for clinical and procedural aspects of the disease, few studies have measured the
      impact CM has on daily activities. OBJECTIVE: The objective of this study was to
      measure the impact that CM has on daily living activities. METHODS: Data was
      analyzed from 798 CM patients gathered by the national Conquer Chiari Patient
      Registry database. RESULTS: Results indicate CM is associated with negative
      impact on daily living and physical activities for patients, even those
      exhibiting mild symptoms. Participants with severe symptoms experience the
      greatest deficit with regards to daily living such as difficulty walking,
      driving, housecleaning and food preparation. CONCLUSIONS: As 96.1% of CM patients
      report impact in one or more areas of daily living, CM is classified as a
      disability according to 42 U.S. CODE S 12101 (Americans with Disabilities Act).
      The degree of self-reported CM symptom severity is strongly related to the
      frequency and extent of limitations in both physical and daily activities.

PMID- 25753309
TI  - Large-Scale Simulation for Teaching Combat and Operational Stress Control:
      Operation Bushmaster.
AB  - Large-scale high-fidelity casualty simulation and exposure to realistic
      environmental stressors in Operation Bushmaster represents a unique teaching
      environment that challenges military medical students to apply skills in
      assessment and acute management of stress responses. While this training event is
      specific to military medical students, the skills demonstrated could be readily
      applied in natural disaster or other mass civilian casualties. Schools seeking to
      teach mass casualty response could implement many of the elements of the
      curriculum outlined in this article on a smaller scale. Doing so exposes students
      to decision making in a disaster where the number of patients exceeds available
      resources and damage to infrastructure may limit their capabilities. Our
      experience with large-scale simulation suggests that this is an effective
      teaching tool.

PMID- 25753310
TI  - Should external short courses be a compulsory part of ACEM specialty training?
      No.
AB  - I am proud to be a product of an excellent training system that builds trainees
      and fellows with an ongoing desire to learn. Dogmatic incorporation of external
      courses into training would be incongruent with medical education best practice
      principles upon which the new curriculum is founded. I am confident that our
      junior colleagues can - as we were - be trusted for generations to come to
      fashion their own learning paths, identifying and addressing their own knowledge
      gaps, using whatever media engages them best.

PMID- 25753311
TI  - 75% success rate after open debridement, exchange of tibial insert, and
      antibiotics in knee prosthetic joint infections.
AB  - BACKGROUND AND PURPOSE: Prosthetic joint infection (PJI) is a leading cause of
      early revision after total knee arthroplasty (TKA). Open debridement with
      exchange of tibial insert allows treatment of infection with retention of fixed
      components. We investigated the success rate of this procedure in the treatment
      of knee PJIs in a nationwide material, and determined whether the results were
      affected by microbiology, antibiotic treatment, or timing of debridement.
      PATIENTS AND METHODS: 145 primary TKAs revised for the first time, due to
      infection, with debridement and exchange of the tibial insert were identified in
      the Swedish Knee Arthroplasty Register (SKAR). Staphylococcus aureus was the most
      common pathogen (37%) followed by coagulase-negative staphylococci (CNS) (23%).
      Failure was defined as death before the end of antibiotic treatment, revision of
      major components due to infection, life-long antibiotic treatment, or chronic
      infection. RESULTS: The overall healing rate was 75%. The type of infecting
      pathogen did not statistically significantly affect outcome. Staphylococcal
      infections treated without a combination of antibiotics including rifampin had a
      higher failure rate than those treated with rifampin (RR = 4, 95% CI: 2-10). In
      the 16 cases with more than 3 weeks of symptoms before treatment, the healing
      rate was 62%, as compared to 77% in the other cases (p = 0.2). The few patients
      with a revision model of prosthesis at primary operation had a high failure rate
      (5 of 8). INTERPRETATION: Good results can be achieved by open debridement with
      exchange of tibial insert. It is important to use an antibiotic combination
      including rifampin in staphylococcal infections.

PMID- 25753312
TI  - Decolorization of Acid Orange 7 by an electric field-assisted modified orifice
      plate hydrodynamic cavitation system: Optimization of operational parameters.
AB  - In this study, the decolorization of Acid Orange 7 (AO-7) with intensified
      performance was obtained using hydrodynamic cavitation (HC) combined with an
      electric field (graphite electrodes). As a preliminary step, various HC systems
      were compared in terms of decolorization, and, among them, the electric field
      assisted modified orifice plate HC (EFM-HC) system exhibited perfect
      decolorization performance within 40 min of reaction time. Interestingly, when
      H2O2 was injected into the EFM-HC system as an additional oxidant, the reactor
      performance gradually decreased as the dosing ratio increased; thus, the
      remaining experiments were performed without H2O2. Subsequently, an optimization
      process was conducted using response surface methodology with a Box-Behnken
      design. The inlet pressure, initial pH, applied voltage, and reaction time were
      chosen as operational key factors, while decolorization was selected as the
      response variable. The overall performance revealed that the selected parameters
      were either slightly interdependent, or had significant interactive effects on
      the decolorization. In the verification test, complete decolorization was
      observed under statistically optimized conditions. This study suggests that EFM
      HC is a useful method for pretreatment of dye wastewater with positive economic
      and commercial benefits.

PMID- 25753313
TI  - Comprehensive experimental and numerical investigations of the effect of
      frequency and acoustic intensity on the sonolytic degradation of naphthol blue
      black in water.
AB  - In the present work, comprehensive experimental and numerical investigations of
      the effects of frequency and acoustic intensity on the sonochemical degradation
      of naphthol blue black (NBB) in water have been carried out. The experiments have
      been examined at three frequencies (585, 860 and 1140 kHz) and over a wide range
      of acoustic intensities. The observed experimental results have been discussed
      using a more realistic approach that combines the single bubble sonochemistry and
      the number of active bubbles. The single bubble yield has been predicted using a
      model that combines the bubble dynamics with chemical kinetics consisting of
      series of chemical reactions (73 reversible reactions) occurring inside an air
      bubble during the strong collapse. The experimental results showed that the
      sonochemical degradation rate of NBB increased substantially with increasing
      acoustic intensity and decreased with increasing ultrasound frequency. The
      numerical simulations revealed that NBB degraded mainly through the reaction with
      hydroxyl radical (OH), which is the dominant oxidant detected in the bubble
      during collapse. The production rate of OH radical inside a single bubble
      followed the same trend as that of NBB degradation rate. It increased with
      increasing acoustic intensity and decreased with increasing frequency. The
      enhancing effect of acoustic intensity toward the degradation of NBB was
      attributed to the rise of both the individual chemical bubble yield and the
      number of active bubbles with increasing acoustic intensity. The reducing effect
      of frequency was attributed to the sharp decrease in the chemical bubble yield
      with increasing frequency, which would not compensated by the rise of the number
      of active bubbles with the increase in ultrasound frequency.

PMID- 25753314
TI  - Crown ether helical peptides are preferentially inserted in lipid bilayers as a
      transmembrane ion channels.
AB  - Oriented circular dichroism was used to study the alignment crown ether-modified
      peptides. The influence of different N- and C-functionalities was assessed using
      at variable peptide:lipid ratios from 1:20 to 1:200. Neither the functionalities
      nor the concentration had any major effect on the orientation. The alignment of
      the 21-mer peptides was also examined with lipid membranes of different bilayer
      thickness. The use of synchrotron radiation as light source allowed the study of
      peptide:lipid molar ratios from 1:20 to 1:1000. For all conditions studied, the
      peptides were found to be predominantly incorporated as a transmembrane helix
      into the membrane, especially at low peptide concentration, but started to
      aggregate on the membrane surface at higher peptide:lipid ratios. The structural
      information on the preferred trans-bilayer alignment of the crown ether
      functional groups explains their ion conductivity and is useful for the further
      development of membrane-active nanochemotherapeutics.

PMID- 25753315
TI  - An obesogenic island in the Mediterranean: mapping potential drivers of obesity
      in Malta.
AB  - OBJECTIVE: The prevalence of childhood and adult obesity in Malta is among the
      highest in the world. Although increasingly recognised as a public health problem
      with substantial future economic implications for the national health and social
      care systems, understanding the context underlying the burden of obesity is
      necessary for the development of appropriate counter-strategies. DESIGN: We
      conducted a contextual analysis to explore factors that may have potentially
      contributed to the establishment of an obesogenic environment in Malta. A search
      of the literature published between 1990 and 2013 was conducted in MEDLINE and
      EMBASE. Twenty-two full-text articles were retrieved. Additional publications
      were identified following recommendations by Maltese public health experts; a
      review of relevant websites; and thorough hand searching of back issues of the
      Malta Medical Journal since 1990. SETTING: Malta. SUBJECTS: Whole population,
      with a focus on children. RESULTS: Results are organised and presented using the
      ANalysis Grid for Elements Linked to Obesity (ANGELO) framework. Physical,
      economic, policy and socio-cultural dimensions of the Maltese obesogenic
      environment are explored. CONCLUSIONS: Malta's obesity rates may be the result of
      an obesogenic environment characterised by limited infrastructure for active
      living combined with an energy-dense food supply. Further research is required to
      identify and quantify the strength of interactions between these potential
      environmental drivers of obesity in order to enable appropriate countermeasures
      to be developed.

PMID- 25753316
TI  - Narrative therapy with an emotional approach for people with depression: Improved
      symptom and cognitive-emotional outcomes.
AB  - ACCESSIBLE SUMMARY: Narrative therapy is a useful approach in the treatment of
      depression that allows that person to 're-author' his/her life stories by
      focusing on positive interpretations, and such focus on positive emotions is a
      crucial component of treatment for depression. This paper evaluates narrative
      therapy with an emotional approach (NTEA) as a therapeutic modality that could be
      used by nurses for persons with depression. A nurse-administered NTEA
      intervention for people with depression appears effective in increasing cognitive
      emotional outcomes, such as hope, positive emotions and decreasing symptoms of
      depression. Thus, NTEA can be a useful nursing intervention strategy for people
      with depression. ABSTRACT: Narrative therapy, which allows a person to 're
      author' his/her life stories by focusing on positive interpretations, and emotion
      focused therapy, which enables the person to realize his/her emotions, are useful
      approaches in the treatment of depression. Narrative therapy with an emotional
      approach (NTEA) aims to create new positive life narratives that focus on
      alternative stories instead of negative stories. The purpose of this study was to
      evaluate the effects of the NTEA programme on people with depression utilizing a
      quasi-experimental design. A total of 50 patients (experimental 24, control 26)
      participated in the study. The experimental group completed eight sessions of the
      NTEA programme. The effects of the programme were measured using a self-awareness
      scale, the Nowotny Hope Scale, the Positive Affect and Negative Affect Scale, and
      the Center for Epidemiological Studies-Depression Scale. The two groups were
      homogeneous. There were significant differences in hope, positive and negative
      emotions, and depression between the experimental and control group. The results
      established that NTEA can be a useful nursing intervention strategy for people
      with depression by focusing on positive experiences and by helping depressed
      patients develop a positive identity through authoring affirmative life stories.

PMID- 25753317
TI  - Development of a LC-MS/MS method for simultaneous determination of metoprolol and
      its metabolites, alpha-hydroxymetoprolol and O-desmethylmetoprolol, in rat
      plasma: application to the herb-drug interaction study of metoprolol and
      breviscapine.
AB  - A simple, specific and sensitive LC-MS/MS method was developed and validated for
      the simultaneous determination of metoprolol (MET), alpha-hydroxymetoprolol (HMT)
      and O-desmethylmetoprolol (DMT) in rat plasma. The plasma samples were prepared
      by protein precipitation, then the separation of the analytes was performed on an
      Agilent HC-C18 column (4.6 * 250 mm, 5 um) at a flow rate of 1.0 mL/min, and post
      column splitting (1:4) was used to give optimal interface flow rates (0.2 mL/min)
      for MS detection; the total run time was 8.5 min. Mass spectrometric detection
      was achieved using a triple-quadrupole mass spectrometer equipped with an
      electrospray source interface in positive ionization mode. The method was fully
      validated in terms of selectivity, linearity, accuracy, precision, stability,
      matrix effect and recovery over a concentration range of 3.42-7000 ng/mL for MET,
      2.05-4200 ng/mL for HMT and 1.95-4000 ng/mL for DMT. The analytical method was
      successfully applied to herb-drug interaction study of MET and breviscapine after
      administration of breviscapine (12.5 mg/kg) and MET (40 mg/kg). The results
      suggested that breviscapine have negligible effect on pharmacokinetics of MET in
      rats; the information may be beneficial for the application of breviscapine in
      combination with MET in clinical therapy.

PMID- 25753318
TI  - Development of neuropeptide analogs capable of traversing the integument: A case
      study using diapause hormone analogs in Helicoverpa zea.
AB  - Diapause hormone and its analogs terminate pupal diapause in Helicoverpa zea when
      injected, but if such agents are to be used as effective diapause disruptors it
      will be essential to develop simple techniques for administering active compounds
      that can exert their effect by penetrating the insect epidermis. In the current
      study, we used two molecules previously shown to have high diapause-terminating
      activity as lead molecules to rationally design and synthesize new amphiphilic
      compounds with modified hydrophobic components. An assay for diapause termination
      identified 13 active compounds with EC50's ranging from 0.9 to 46.0 pmol per
      pupa. Three compounds, Decyl-1963, Dodecyl-1967, and Heptyl-1965, selected from
      the 13 compounds most active in breaking diapause following injection, also
      successfully prevented newly-formed pupae from entering diapause when applied
      topically. These compounds feature straight-chain, aliphatic hydrocarbons from 7
      to 12 carbons in length; DH analogs with either a short-chain length of 4 or an
      aromatic phenethyl group failed to act topically. Compared to a high diapause
      incidence of 80-90% in controls, diapause incidence in pupae receiving a 10 nmole
      topical application of Decyl-1963, Dodecyl-1967, or Heptyl-1965 dropped to 30
      45%. Decyl-1963 and Dodecyl-1967 also remained effective when topically applied
      at the 1 nmole level. These results suggest the feasibility of developing DH
      agonists that can be applied topically and suggest the identity of new lead
      molecules for development of additional topically-active DH analogs. The ability
      to penetrate the insect epidermis and/or midgut lining is critical if such agents
      are to be considered for future use as pest management tools. 

PMID- 25753320
TI  - What is substance abuse? And should we screen all pregnant women for substance
      abuse?

PMID- 25753319
TI  - Changes in short-chain acyl-coA dehydrogenase during rat cardiac development and
      stress.
AB  - This study was designed to investigate the expression of short-chain acyl-CoA
      dehydrogenase (SCAD), a key enzyme of fatty acid beta-oxidation, during rat heart
      development and the difference of SCAD between pathological and physiological
      cardiac hypertrophy. The expression of SCAD was lowest in the foetal and neonatal
      heart, which had time-dependent increase during normal heart development. In
      contrast, a significant decrease in SCAD expression was observed in different
      ages of spontaneously hypertensive rats (SHR). On the other hand, swim-trained
      rats developed physiological cardiac hypertrophy, whereas SHR developed
      pathological cardiac hypertrophy. The two kinds of cardiac hypertrophy exhibited
      divergent SCAD changes in myocardial fatty acids utilization. In addition, the
      expression of SCAD was significantly decreased in pathological cardiomyocyte
      hypertrophy, however, increased in physiological cardiomyocyte hypertrophy. SCAD
      siRNA treatment triggered the pathological cardiomyocyte hypertrophy, which
      showed that the down-regulation of SCAD expression may play an important role in
      pathological cardiac hypertrophy. The changes in peroxisome proliferator
      activated receptor alpha (PPARalpha) was accordant with that of SCAD. Moreover,
      the specific PPARalpha ligand fenofibrate treatment increased the expression of
      SCAD and inhibited pathological cardiac hypertrophy. Therefore, we speculate that
      the down-regulated expression of SCAD in pathological cardiac hypertrophy may be
      responsible for 'the recapitulation of foetal energy metabolism'. The
      deactivation of PPARalpha may result in the decrease in SCAD expression in
      pathological cardiac hypertrophy. Changes in SCAD are different in pathological
      and physiological cardiac hypertrophy, which may be used as the molecular markers
      of pathological and physiological cardiac hypertrophy. 

PMID- 25753321
TI  - Magnetic property, DFT calculation, and biological activity of bis[(MU(2)
      chloro)chloro(1,10-phenanthroline)copper(II)] complex.
AB  - The dinuclear complex bis[(MU(2)-chloro)chloro(1,10-phenanthroline)copper(II)]
      (1) was synthesized, and characterized by X-ray, FTIR and thermal analysis. The
      fitting of magnetic susceptibility and magnetization curve of (1) indicates the
      occurrence of weak antiferromagnetic exchange interaction between copper(II)
      ions. The electronic structure has been also determined by density functional
      theory (DFT) method. Complex (1) displayed potent anticancer activity against B16
      (Melanoma), MDA-MB-32 (Breast Adenocarcinoma), A549 (Lung Adenocarcinoma), HT-29
      (Colon Adenocarcinoma) and SF (Astrocytoma) cell lines with an average IC50 value
      of 0.726 MUg/ml compared to 4.88 MUg/ml for cisplatin. Complex (1) has a better
      therapeutic index and toxicological profile than cisplatin, and has demonstrated
      a potential chemotherapeutic property.

PMID- 25753322
TI  - Rutin ameliorates cyclophosphamide induced oxidative stress and inflammation in
      Wistar rats: role of NFkappaB/MAPK pathway.
AB  - Cyclophosphamide is a potent anticancer agent. However its clinical use is
      restricted because of its marked organ toxicity associated with increased
      oxidative stress and inflammation. The present study was designed to demonstrate
      the protective effects of rutin, a naturally occurring bioflavonoid against the
      hepatotoxicity induced by CP. Rats were subjected to oral pretreatment of rutin
      (50 and 100 mg/kg b wt) against hepatotoxicity induced by i.p. injection of CP
      (150 mg/kg b wt) and were sacrificed after 24 h. Hepatoprotective effects of
      rutin were associated with upregulation of antioxidant enzyme activities and down
      regulation of serum toxicity markers. Rutin was able to down regulate the levels
      of inflammatory markers like TNF-alpha, IL-6 and expressions of p38-MAPK,
      NFkappaB, i-NOS and COX-2. Histopathological changes further confirmed the
      biochemical and immunohistochemical results showing that CP caused significant
      structural damage to liver which were reversed by pretreatment of rutin.
      Therefore, our study revealed that rutin may be a promising modulator in
      attenuating CP induced oxidative stress, inflammation and hepatotoxicity via
      targeting NFkappaB and MAPK pathway.

PMID- 25753323
TI  - Hepato-protective effects of six schisandra lignans on acetaminophen-induced
      liver injury are partially associated with the inhibition of CYP-mediated
      bioactivation.
AB  - Acetaminophen (APAP) overdose is the most frequent cause of drug-induced acute
      liver failure. Schisandra fructus is widely-used traditional Chinese medicine
      which possesses hepato-protective potential. Schisandrin A (SinA), Schisandrin B
      (SinB), Schisandrin C (SinC), Schisandrol A (SolA), Schisandrol B (SolB), and
      Schisantherin A (SthA) are the major bioactive lignans. Most recently, we found
      SolB exerts significant hepato-protection against APAP-induced liver injury. In
      this study, the protective effects of the other five schisandra lignans against
      APAP-induced acute hepatotoxicity in mice were investigated and compared with
      that of SolB. The results of morphological and biochemical assessment clearly
      demonstrated significant protective effects of SinA, SinB, SinC, SolA, SolB, and
      SthA against APAP-induced liver injury. Among these schisandra lignans, SinC and
      SolB exerted the strongest hepato-protective effects against APAP-induced
      hepatotoxicity. Six lignans pretreatment before APAP dosing could prevent the
      depletions of total liver glutathione (GSH) and mitochondrial GSH caused by APAP.
      Additionally, the lignans treatment inhibited the enzymatic activities of three
      CYP450 isoforms (CYP2E1, CYP1A2, and CYP3A11) related to APAP bioactivation, and
      further decreased the formation of APAP toxic intermediate N-acetyl-p
      benzoquinone imine (NAPQI) in mouse microsomal incubation system. This study
      demonstrated that SinA, SinB, SinC, SolA, SolB and SthA exhibited significant
      protective actions toward APAP-induced liver injury, which was partially
      associated with the inhibition of CYP-mediated APAP bioactivation. 

PMID- 25753324
TI  - Vincristine activates c-Jun N-terminal kinase in chronic lymphocytic leukaemia in
      vivo.
AB  - AIMS: The authors' aim was to conduct a proof-of-principle study to test whether
      c-Jun N-terminal kinase (JNK) phosphorylation and Noxa induction occur in
      peripheral blood chronic lymphocytic leukaemia (CLL) cells in patients receiving
      a vincristine infusion. METHODS: Patients with CLL received 2 mg vincristine by a
      5-min intravenous infusion. Blood samples were collected at baseline and up to 6
      h after the vincristine infusion, and assayed for JNK activation, Noxa induction
      and vincristine plasma concentrations. RESULTS: Ex vivo treated peripheral CLL
      cells activated JNK in response to 10-100 nM vincristine in 6 h. Noxa protein
      expression, while variable, was also observed over this time frame. In CLL
      patients, vincristine infusion led to rapid (<1 h) JNK phosphorylation in
      peripheral blood CLL cells which was sustained for at least 4-6 h after the
      vincristine infusion. Noxa protein expression was not observed in response to
      vincristine infusion. CONCLUSIONS: This study confirmed that vincristine can
      activate JNK but not induce Noxa in CLL cells in vivo. The results suggest that
      novel JNK-dependent drug combinations with vincristine warrant further
      investigation.

PMID- 25753325
TI  - Neutrophil/Lymphocyte Ratio Can Predict Postoperative Mortality in Patients with
      Chronic Thromboembolic Pulmonary Hypertension.
AB  - OBJECTIVE: The aim of our study was to investigate clinical importance of
      neutrophil/ lymphocyte ratio in patients with Chronic thromboembolic pulmonary
      hypertension. METHODS: 125 consecutive patients with a diagnosis of Chronic
      thromboembolic pulmonary hypertension were operated pulmonary
      thromboendarterectomy in our center between February 2011 and August 2013. 106
      patients included into the study due to limitations. The patients were classified
      into two groups as patients discharged alive (Group 1) and those dying in the
      hospital (Group 2). Baseline neutrophil/lymphocyte ratio level was measured by
      dividing neutrophil count to lymphocyte count. RESULTS: 84 patients (79%) were in
      Group 1, 22 patients (21%) were in Group 2. Patients with higher
      neutrophil/lymphocyte ratio in admission have a significantly higher mortality
      rate and postoperative pulmonary vascular resistance was found statistically
      significant variable to predict the mortality. Receiver operator characteristic
      (ROC) analysis revealed that using a cut-off point of 2.54, admission
      neutrophil/lymphocyte ratio predicts mortality. Also, correlation analysis showed
      a significant correlation between preoperative pulmonary vascular resistance and
      neutrophil/lymphocyte ratio. CONCLUSION: The neutrophil/lymphocyte ratio level
      may be a useful and noninvasive biomarker for operative risk stratification for
      mortality after pulmonary thromboendarterectomy.

PMID- 25753326
TI  - Coronary Bypass Surgery in Patients with Pulmonary Hypertension: Assessment of
      Early and Long Term Results.
AB  - PURPOSE: We aimed to evaluate the effects of preoperative pulmonary hypertension
      (PH) on early and long term results in patients undergoing coronary bypass
      surgery and the effects of coronary bypass surgery on PH. METHODS: Among 2325
      patients who underwent elective isolated coronary artery bypass surgery between
      March 2003 and March 2012, 287 patients with high preoperative pulmonary arterial
      pressure (PAP) >=30 mmHg were examined. Patients' data were obtained by
      retrospective examination of our clinic's database. 69 patients who had complete
      parameters included in the study. RESULTS: There was no increase in the New York
      Heart Association (NYHA) functional classification 84% of cases. Preoperative and
      postoperative values of the mean ejection fraction and mean PAP of patients was
      respectively 45.28 +/- 9.67 (25-65), 46.03 +/-12.4 (20-65) (p = 0.447), 36.67 +/-
      6.81 (30-60) mmHg, 37.81 +/- 10.07 (20-70) mmHg (p = 0.378). The late mortality
      of cases was 5.79%. In our study, during 33.9 +/- 17 (9-100) months follow up
      period, life expectancy was calculated as 94.7 months. CONCLUSION: Preoperative
      evaluation of these patients for appropriate medical treatment at peroperative
      and postoperative period, coronary bypass can be performed with low morbidity and
      mortality rates. In the late period after surgical revascularization PH showed no
      significant change and had no adverse effect on quality of life.

PMID- 25753327
TI  - United Kingdom immune thrombocytopenia registry: retrospective evaluation of bone
      marrow fibrosis in adult patients with primary immune thrombocytopenia and
      correlation with clinical findings.
AB  - Fibrosis has been reported in some patients with immune thrombocytopenia (ITP)
      treated with thrombopoietin receptor agonists (TPO-RA). However, fibrosis has
      also been reported in patients with various stages of ITP, who were TPO-RA
      treatment-naive. In our study, we looked for fibrosis in bone marrow trephine
      biopsies taken at initial diagnosis from 32 adult patients with ITP. Ten of the
      32 evaluated samples (31.25%) showed increased reticulin (Grade 1-2 on
      Bauermeister scale and Grade 0-1 on the European Consensus scale), which showed a
      positive correlation with ethnicity (0.3%) but did not correlate with disease
      severity, any clinical features or co-morbidities. 

PMID- 25753328
TI  - Pheophorbide-a conjugates with cancer-targeting moieties for targeted
      photodynamic cancer therapy.
AB  - Pheophorbide-a, a non-selective photosensitizer, was conjugated with cancer
      targeting moieties, such as folic acid, the CRGDLASLC peptide, the cRGDfK peptide
      and leuprorelin, for the purpose of targeted photodynamic cancer therapy. The
      cellular uptake of pheophorbide-a conjugates in cancer cells overexpressing the
      corresponding receptors of the targeting moieties was largely enhanced compared
      with that in the receptor-negative cells. In the study of in vitro photodynamic
      activity and selectivity of pheophorbide-a conjugates in the receptor-positive
      and receptor-negative cells, a pheophorbide-a conjugate, (14) with an alphavbeta6
      ligand (CRGDLASLC) exhibited the highest selectivity in the positive FaDu cells.
      Targeted PDT with 14 induced cell death through apoptosis and morphological
      apoptosis-like characteristics. These results suggest that pheophorbide-a
      conjugate 14 could be utilized in selective photodynamic therapy for oral cancers
      primarily expressing the alphavbeta6 receptor. 

PMID- 25753329
TI  - Synthesis of 6-aryl-substituted sulfocoumarins and investigation of their
      carbonic anhydrase inhibitory action.
AB  - A series of 6-aryl-substituted 1,2-benzoxathiine 2,2-dioxides was obtained by
      reacting 6-iodo-sulfocoumarin with arylboronic acids in Suzuki cross-coupling
      conditions. The new sulfocoumarins incorporating various substituted phenyl
      moieties in position 6 of the heterocyclic ring were investigated for the
      inhibition of four human (h) carbonic anhydrase (CA, EC 4.2.1.1) isoforms with
      medicinal chemistry applications, the cytosolic hCA I and II, and the
      transmembrane, tumor-associated hCA IX and XII. The aryl-substituted
      sulfocoumarins did not inhibit the ubiquitous, off-target cytosolic isoforms hCA
      I and II (KIs>10MUM) but showed effective inhibition against the two
      transmembrane CAs, with KIs ranging from 9.0 to 95.3nM against hCA IX, and
      between 3.5 and 14.2nM against hCA XII. As hCA IX and XII are validated anti
      tumor targets, such sulfocoumarin, isoform-selective inhibitors may be useful for
      identifying suitable drug candidates for further clinical trials of this class of
      pharmacologic agents.

PMID- 25753331
TI  - Periostin: a potent chemotactic factor for recruiting tumor-associated
      macrophage.

PMID- 25753330
TI  - Novel curcumin analogs to overcome EGFR-TKI lung adenocarcinoma drug resistance
      and reduce EGFR-TKI-induced GI adverse effects.
AB  - Curcumin (1) down-regulates the expression as well as phosphorylation of
      epidermal growth factor receptor (EGFR) in lung adenocarcinoma cells expressing
      gefitinib-resistant EGFR. Thirty-seven newly synthesized curcumin analogues
      including dimethoxycurcumin (2, DMC) were evaluated for their effects on EGFR
      expression as well as phosphorylation in two gefitinib-resistant lung
      adenocarcinoma cell lines, CL1-5 (EGFR(wt)) and H1975 (EGFR(L858R+T790M)). Based
      on the identified structure-activity relationships, methoxy substitution at C-3',
      C-4', or both positions favored inhibitory activity (compounds 1, 2, 5, 8-15, 17,
      36), while compounds with more polar substituents were generally less active in
      both cell lines. Compound 36 with a fluorine substituent at C-6' and its
      protonated counterpart 2 did not lose activity, suggesting halogen tolerance. In
      addition, a conjugated linker was essential for activity. Among all evaluated
      curcumin derivatives, compound 2 showed the best inhibitory effects on both wild
      type and mutant EGFR by efficiently inducing gefitinib-insensitive EGFR
      degradation. Compound 23 also reduced gefitinib-induced gastrointestinal damage
      in the non-transformed intestinal epithelial cell line IEC-18. 

PMID- 25753332
TI  - Mitochondrial calcium uniporter protein MCU is involved in oxidative stress
      induced cell death.
AB  - Mitochondrial calcium uniporter (MCU) is a conserved Ca(2+) transporter at
      mitochondrial in eukaryotic cells. However, the role of MCU protein in oxidative
      stress-induced cell death remains unclear. Here, we showed that ectopically
      expressed MCU is mitochondrial localized in both HeLa and primary cerebellar
      granule neurons (CGNs). Knockdown of endogenous MCU decreases mitochondrial
      Ca(2+) uptake following histamine stimulation and attenuates cell death induced
      by oxidative stress in both HeLa cells and CGNs. We also found MCU interacts with
      VDAC1 and mediates VDAC1 overexpression-induced cell death in CGNs. This finding
      demonstrates that MCU-VDAC1 complex regulates mitochondrial Ca(2+) uptake and
      oxidative stress-induced apoptosis, which might represent therapeutic targets for
      oxidative stress related diseases. 

PMID- 25753333
TI  - A New Enzyme-linked Sorbent Assay (ELSA) to Quantify Syncytiotrophoblast
      Extracellular Vesicles in Biological Fluids.
AB  - PROBLEM: The pregnancy-associated disease preeclampsia is related to the release
      of syncytiotrophoblast extracellular vesicles (STBEV) by the placenta. To improve
      functional research on STBEV, reliable and specific methods are needed to
      quantify them. However, only a few quantification methods are available and
      accepted, though imperfect. For this purpose, we aimed to provide an enzyme
      linked sorbent assay (ELSA) to quantify STBEV in fluid samples based on their
      microvesicle characteristics and placental origin. METHOD OF STUDY: Ex vivo
      placenta perfusion provided standards and samples for the STBEV quantification.
      STBEV were captured by binding of extracellular phosphatidylserine to immobilized
      annexin V. The membranous human placental alkaline phosphatase on the STBEV
      surface catalyzed a colorimetric detection reaction. RESULTS AND CONCLUSION: The
      described ELSA is a rapid and simple method to quantify STBEV in diverse liquid
      samples, such as blood or perfusion suspension. The reliability of the ELSA was
      proven by comparison with nanoparticle tracking analysis.

PMID- 25753334
TI  - From gross anatomy to the nanomorphome: stereological tools provide a paradigm
      for advancing research in quantitative morphomics.
AB  - The terms morphome and morphomics are not new but, recently, a group of
      morphologists and cell biologists has given them clear definitions and emphasised
      their integral importance in systems biology. By analogy to other '-omes', the
      morphome refers to the distribution of matter within 3-dimensional (3D) space. It
      equates to the totality of morphological features within a biological system
      (virus, single cell, multicellular organism or populations thereof) and
      morphomics is the systematic study of those structures. Morphomics research has
      the potential to generate 'big data' because it includes all imaging techniques
      at all levels of achievable resolution and all structural scales from gross
      anatomy and medical imaging, via optical and electron microscopy, to molecular
      characterisation. As with other '-omics', quantification is an important part of
      morphomics and, because biological systems exist and operate in 3D space, precise
      descriptions of form, content and spatial relationships require the
      quantification of structure in 3D. Revealing and quantifying structural detail
      inside the specimen is achieved currently in two main ways: (i) by some form of
      reconstruction from serial physical or tomographic slices or (ii) by using
      randomly-sampled sections and simple test probes (points, lines, areas, volumes)
      to derive stereological estimates of global and/or individual quantities. The
      latter include volumes, surfaces, lengths and numbers of interesting features and
      spatial relationships between them. This article emphasises the value of
      stereological design, sampling principles and estimation tools as a template for
      combining with alternative imaging techniques to tackle the 'big data' issue and
      advance knowledge and understanding of the morphome. The combination of
      stereology, TEM and immunogold cytochemistry provides a practical illustration of
      how this has been achieved in the sub-field of nanomorphomics. Applying these
      quantitative tools/techniques in a carefully managed study design offers us a
      deeper appreciation of the spatiotemporal relationships between the genome,
      metabolome and morphome which are integral to systems biology. 

PMID- 25753335
TI  - Voluntary rewards mediate the evolution of pool punishment for maintaining public
      goods in large populations.
AB  - Punishment is a popular tool when governing commons in situations where free
      riders would otherwise take over. It is well known that sanctioning systems, such
      as the police and courts, are costly and thus can suffer from those who free ride
      on other's efforts to maintain the sanctioning systems (second-order free
      riders). Previous game-theory studies showed that if populations are very large,
      pool punishment rarely emerges in public good games, even when participation is
      optional, because of second-order free riders. Here we show that a matching fund
      for rewarding cooperation leads to the emergence of pool punishment, despite the
      presence of second-order free riders. We demonstrate that reward funds can pave
      the way for a transition from a population of free riders to a population of pool
      punishers. A key factor in promoting the transition is also to reward those who
      contribute to pool punishment, yet not abstaining from participation. Reward
      funds eventually vanish in raising pool punishment, which is sustainable by
      punishing the second-order free riders. This suggests that considering the
      interdependence of reward and punishment may help to better understand the
      origins and transitions of social norms and institutions. 

PMID- 25753336
TI  - Temperature-dependent lipid metabolism in the blow fly Lucilia sericata.
AB  - An understanding of how arthropods use energy is fundamental to explaining their
      diverse life histories and adaptation to specific environments. It is also of
      importance when attempting to predict the impacts of environmental change on
      patterns of development and phenology. Here, lipid use by the economically
      important agent of ovine myiasis, Lucilia sericata (Diptera: Calliphoridae), was
      quantified at a range of temperatures. During pupation, at temperatures above the
      minimum temperature required for development (9  degrees C), pupae depleted an
      average of 30% of their total lipid over the course of pupation regardless of
      temperature. There was no detectable loss of lipid during pupation at
      temperatures below 9  degrees C. In general, larger individuals had the same
      relative amounts of lipid as smaller individuals. Newly emerged adults
      metabolized about 16% of the lipid reserves with which they emerged in the first
      24 h during flight-related activity. Starved adults, with access to water but
      without sucrose or protein, depleted their lipid reserves and died within about 4
      days of emergence. However, adults with access to protein and/or carbohydrate
      were able to maintain a stored lipid content of about 2.38% of their total body
      mass for at least 14 days after emergence, irrespective of sex. This finding is
      similar to that in field-caught individuals, in which lipid content was found to
      be a mean of 3% of body mass. The data suggest that warmer environmental
      conditions, within the temperature limits tested here, although shortening the
      time required for development and altering the patterns of seasonal abundance of
      L. sericata, are unlikely to impact on fly survival because of greater metabolic
      demands during non-feeding stages of the lifecycle. 

PMID- 25753337
TI  - Understanding fungal functional biodiversity during the mitigation of
      environmentally dispersed pentachlorophenol in cork oak forest soils.
AB  - Pentachlorophenol (PCP) is globally dispersed and contamination of soil with this
      biocide adversely affects its functional biodiversity, particularly of fungi -
      key colonizers. Their functional role as a community is poorly understood,
      although a few pathways have been already elucidated in pure cultures. This
      constitutes here our main challenge - elucidate how fungi influence the pollutant
      mitigation processes in forest soils. Circumstantial evidence exists that cork
      oak forests in N. W. Tunisia - economically critical managed forests are likely
      to be contaminated with PCP, but the scientific evidence has previously been
      lacking. Our data illustrate significant forest contamination through the
      detection of undefined active sources of PCP. By solving the taxonomic diversity
      and the PCP-derived metabolomes of both the cultivable fungi and the fungal
      community, we demonstrate here that most strains (predominantly penicillia)
      participate in the pollutant biotic degradation. They form an array of
      degradation intermediates and by-products, including several hydroquinone,
      resorcinol and catechol derivatives, either chlorinated or not. The degradation
      pathway of the fungal community includes uncharacterized derivatives, e.g.
      tetrachloroguaiacol isomers. Our study highlights fungi key role in the
      mineralization and short lifetime of PCP in forest soils and provide novel tools
      to monitor its degradation in other fungi dominated food webs. 

PMID- 25753338
TI  - Insulin resistance is associated with all chronic complications in type 1
      diabetes.
AB  - BACKGROUND: Insulin resistance (IR) is present in type 1 diabetes mellitus (T1DM)
      and is suggested to be related to chronic diabetic complications. The primary aim
      of our study was to assess IR in T1DM patients with and without chronic
      complications. A secondary aim was to evaluate the possible association between
      IR and chronic diabetic complications. METHODS: This cross-sectional study
      enrolled 272 patients with T1DM. Insulin resistance was quantified using the
      estimated glucose disposal rate (eGDR). Associations between eGDR and each
      diabetes complication were first evaluated using binary logistic regression, then
      multiparametric logistic regression with stepwise selection of covariates. The
      discriminative value of eGDR was assessed by receiver operating characteristic
      (ROC) curve analysis. RESULTS: Estimated GDR was lower in patients with chronic
      diabetic complications (6.1 vs. 6.9 mg/kg per min [P = 0.02] for retinopathy; 6.3
      vs. 7.3 mg/kg per min [P < 0.01] for nephropathy; 6.5 vs. 7.6 mg/kg per min [P <
      0.01] for neuropathy; and 5.2 vs. 7.5 mg/kg per min [P < 0.01] for cardiovascular
      complications). In univariate analysis eGDR was associated all diabetic
      complications. These associations remained significant after adjustment for
      different variables in the final regression models. In addition, eGDR was a good
      discriminator for each diabetic complication, with an area under the curve
      between 0.609 and 0.759. CONCLUSIONS: Patients with chronic diabetic
      complications are more insulin resistant than those without complications.
      Moreover, IR was independently associated with the presence of each chronic
      diabetic complication, and seems to be a good discriminator for them all.

PMID- 25753342
TI  - Toxicity of anthraquinones: differential effects of rumex seed extracts on rat
      organ weights and biochemical and haematological parameters.
AB  - The genus Rumex and related species such as Rheum and Polygonum are widely used
      as medicinal herbs and foods. They contain anthraquinones (AQ) such as emodin and
      chrysophanol as active ingredients, and there is concern about the toxicity of
      these compounds. This study evaluated the chronic effects of Rumex patientia seed
      aqueous and ethanolic extracts, in male and female rats separately, on organ
      weights and over 30 haematological, biochemical and histological parameters,
      immediately after 14-week administration and after a further period of 15 days
      without drug treatment. Adverse changes were associated with long-term AQ
      administration, and these focussed on the liver, lung and kidney, but after 15
      day convalescence, most had reverted to normal. In general, male rats appeared to
      be more susceptible than female rats at similar doses. The water extract produced
      no irreversible changes, which may reflect the lower dose of the AQ constituents
      or the presence of different ancillary compounds, and supports the traditional
      method of extracting Rumex seeds with water. In conclusion, ethanolic extracts of
      R. patientia caused irreversible pathological changes at very high doses
      (4000mg/kg), but lower doses and aqueous extracts produced either non-significant
      or reversible changes. Long-term administration of high doses of AQ extracts over
      a long period of time should be avoided until further assurances can be given,
      and given other existing reports of reproductive toxicity, should be avoided
      altogether during pregnancy.

PMID- 25753343
TI  - Noninvasive imaging in the assessment of the cardiopulmonary vascular unit.

PMID- 25753344
TI  - The heart is just a muscle.

PMID- 25753345
TI  - ECG Response: March 10, 2015.

PMID- 25753346
TI  - Atresia of the ascending aorta in hypoplastic left heart syndrome.

PMID- 25753347
TI  - Extensive myocardial fibrosis after high-voltage electric shock demonstrated by
      delayed-enhancement cardiac magnetic resonance imaging.

PMID- 25753348
TI  - Letter by Dandel et al regarding article, "systolic and diastolic mechanics in
      stress cardiomyopathy".

PMID- 25753349
TI  - Letter by Madias regarding article, "systolic and diastolic mechanics in stress
      cardiomyopathy".

PMID- 25753350
TI  - Letter by Liu regarding article, "systolic and diastolic mechanics in stress
      cardiomyopathy".

PMID- 25753351
TI  - Response to letters regarding article, "systolic and diastolic mechanics in
      stress cardiomyopathy".

PMID- 25753352
TI  - Improving Chinese nursing students' communication skills by utilizing video
      stimulated recall and role-play case scenarios to introduce them to the SBAR
      technique.
AB  - PURPOSE: Effective communication among healthcare workers is critically important
      for patient safety and quality care. The purpose of this pilot study was to
      evaluate outcomes of a workshop designed to teach Chinese nursing students to use
      the Situation-Background-Assessment-Recommendation (SBAR) communication tool and
      examine their attitudes toward utilizing SBAR as a communication tool. METHOD: A
      convenience sample of 18 master's degree nursing students at a Chinese university
      was introduced to SBAR through a workshop. The workshop combined the SBAR tool,
      video-stimulated recall and role-play case scenarios to illustrate potential
      positive and negative communication-related patient outcomes. Students completed
      a 12-item questionnaire before and after participating in the workshop. Four of
      the items examined the four elements of the SBAR tool (situation, background,
      assessment, recommendation, score range 0-20), and eight of the items evaluated
      students' self-perceived attitudes towards utilizing the SBAR tool in their
      clinical practice (score range 0-40). RESULTS: Pre- and post-workshop scores on
      the four elements of the SBAR tool demonstrate significant improvement in
      knowledge of SBAR (14.0+/-2.9 vs. 16.6+/-2.2, respectively; p=0.009). Pre- and
      post-workshop scores on the items testing students' self-perceived abilities also
      demonstrate significant improvement (26.9+/-3.5 vs. 32.6+/-4.5, respectively;
      p<0.01) in using SBAR. Total scores increased significantly from 40.9+/-5.0 to
      49.2+/-5.9 (p<0.01). Moreover, 93.8% of the students agreed and strongly agreed
      that they would use SBAR during clinical practice. CONCLUSION: Participating in
      the SBAR workshop in combination with video-stimulated recall and role-play case
      scenarios significantly improved the Chinese nursing students' knowledge of SBAR
      and their self-perceived attitudes towards using SBAR tool. Future studies using
      a larger sample size and longer post-workshop follow-up are needed to confirm the
      long-term benefits of the workshop.

PMID- 25753353
TI  - Applying Technological Pedagogical and Content Knowledge (TPACK) model to develop
      an online English writing course for nursing students.
AB  - BACKGROUND: Learning English as foreign language and computer technology are two
      crucial skills for nursing students not only for the use in the medical
      institutions but also for the communication needs following the trend of
      globalization. Among language skills, writing has long been ignored in the
      curriculums although it is a core element of language learning. OBJECTIVES: To
      apply the TPACK (Technological Pedagogical and Content Knowledge) model to design
      an online English writing course for nursing students, and to explore the effects
      of the course to the students' learning progress as well as their satisfactions
      and perceptions. RESEARCH METHODS: A single-group experimental study, utilizing
      the CEEC (College Entrance Examination Center) writing grading criteria and a
      self-designed course satisfaction questionnaire, is used. Fifty one nursing
      students who were in their first/four semesters of the two year vocational pre
      registration nursing course in a Taiwan university were selected using
      convenience sampling. DATA ANALYSIS METHODS: Quantitative data were analyzed
      using descriptive statistics and repeated measure MANOVA. Qualitative data were
      analyzed by content analysis. RESULTS: Students' writing competence had been
      improved significantly in every dimension after the instruction. Only half of the
      learners preferred online writing compared to the traditional way of writing by
      hand. Additionally, participants reported that they would prefer to receive
      feedback from the teacher than peers, yet they did not like the indirect
      feedback. The teacher perceived the course as meaningful but demanding for both
      learning and teaching sides. To implement the peer review activities and give
      feedback on time were two major challenges during the cycles. CONCLUSIONS: The
      TPACK model suggests a comprehensive and effective teaching approach that can
      help enhance nursing students' English writing performance. Teachers are advised
      to consider its implementation when designing their syllabus.

PMID- 25753354
TI  - The regulation of TNFalpha production after heat and endotoxin stimulation is
      dependent on Annexin-A1 and HSP70.
AB  - Febrile temperatures can induce stress responses which protect cells from damage
      and can reduce inflammation during infections and sepsis. However, the mechanisms
      behind the protective functions of heat in response to the bacterial endotoxin
      LPS are unclear. We have recently shown that Annexin-1 (ANXA1)-deficient
      macrophages exhibited higher TNFalpha levels after LPS stimulation. Moreover, we
      have previously reported that ANXA1 can function as a stress protein. Therefore
      in this study, we determined if ANXA1 is involved in the protective effects of
      heat on cytokine levels in macrophages after heat and LPS. Exposure of
      macrophages to 42  degrees C for 1 h prior to LPS results in an inhibition of
      TNFalpha production, which was not evident in ANXA1(-/-) macrophages. We show
      that this regulation involves primarily MYD88-independent pathways. ANXA1
      regulates TNFalpha mRNA stability after heat and LPS, and this is dependent on
      endogenous ANXA1 expression and not exogenously secreted factors. Further
      mechanistic studies revealed the possible involvement of the heat shock protein
      HSP70 and JNK in the heat and inflammatory stress response regulated by ANXA1.
      This study shows that ANXA1, an immunomodulatory protein, is critical in the heat
      stress response induced after heat and endotoxin stimulation.

PMID- 25753356
TI  - Perspectives on the importance of postoperative ileus.
AB  - Post-operative ileus (POI) is a common condition after surgery. Failure to
      restore adequate bowel function after surgery generates a series of complications
      and it is associated to patients frustration and discomfort, worsening their
      perioperative experience. Even mild POI can be source of anxiety and could be
      perceived as a drop out from the "straight-forward" pathway. Enhanced recovery
      programmes have emphasized the importance of early commencement of oral diet,
      avoiding the ancient dogmata of prolonged gastric decompression and fasting.
      These protocols with early oral feeding and mobilization have led to improved
      perioperative management and have decreased hospital length of stay, ameliorating
      patient's postoperative experience as well. Nonetheless, the incidence of POI is
      still high especially after major open abdominal surgery. In order to decrease
      the incidence of POI, minimally-invasive surgical approaches and minimization of
      surgical manipulation have been suggested. From a pharmacological perspective, a
      meta-analysis of pro-kinetics showed beneficial results with alvimopan, although
      its use has been limited by the augmented risk of myocardial infarction and the
      high costs. A more simple approach based on the postoperative use of chewing-gum
      has provided some benefits in restoring bowel function. From an
      anaesthesiological perspective, epidural anaesthesia/analgesia does not only
      reduce the postoperative consumption of systemic opioids but directly improve
      gastrointestinal function and should be considered where possible, at least for
      open surgical procedures. POI represents a common and debilitating complication
      that should be challenged with multi-disciplinary approach. Prospective research
      is warranted on this field and should focus also on patient s reported outcomes.

PMID- 25753357
TI  - Identification of antrodin B from Antrodia camphorata as a new anti
      hepatofibrotic compound using a rapid cell screening method and biological
      evaluation.
AB  - AIM: Liver fibrosis is the excessive accumulation of extracellular matrix (ECM)
      resulting from chronic liver diseases. Efficient and well-tolerated drugs for its
      treatment are urgently needed. This study aims to identify the active ingredients
      of Antrodia camphorata by a bioassay-guided fractionation approach and explore
      the acting mechanism by using a hepatic stellate cell (HSC) line CFSC-8B
      stimulated by transforming growth factor-beta1 (TGF-beta1). METHODS: The
      accumulation of collagens was evaluated using chromogenic precipitation reaction
      with picro-sirius red (PSR) dye solution and quantified by spectrophotometric
      analysis of the dissolved stain. MTT assay, cell migration assay, quantitative
      polymerase chain reaction and western blotting analysis were used to determine
      the cell viability, cell migration and gene expression. RESULTS: We established a
      rapid colorimetric assay suitable for screening of anti-hepatofibrotic reagents.
      Stimulation with 10 ng/mL TGF-beta1 for 48 h and 200 MUL PSR dye solution were
      optimal for the colorimetric assay in CFSC-8B cells. We used SB431542, silybin
      and another 11 antifibrotic reagents to verify the cellular model. Within the
      safe doses, they attenuated ECM production induced by TGF-beta1. Bioactivity
      guided fractionation led to the identification of antrodin B from A. camphorata.
      Antrodin B significantly ameliorated cell proliferation, cell migration,
      suppressed HSC activation marker alpha-smooth muscle actin expression and ECM
      components Col1, Col3 and Fn expression, and blocked the phosphorylation of
      Smad2/3 induced by TGF-beta1 in CFSC-8B cells in a dose-dependent manner.
      CONCLUSION: We developed a simple assay based on TGF-beta1-induced total collagen
      accumulation in CFSC-8B cells and identified antrodin B which may serve as a
      potential candidate for treatment of liver fibrosis.

PMID- 25753355
TI  - Organization of TNIK in dendritic spines.
AB  - Tumor necrosis factor receptor-associated factor 2 (TRAF2)- and noncatalytic
      region of tyrosine kinase (NCK)-interacting kinase (TNIK) has been identified as
      an interactor in the psychiatric risk factor, Disrupted in Schizophrenia 1
      (DISC1). As a step toward deciphering its function in the brain, we performed
      high-resolution light and electron microscopic immunocytochemistry. We
      demonstrate here that TNIK is expressed in neurons throughout the adult mouse
      brain. In striatum and cerebral cortex, TNIK concentrates in dendritic spines,
      especially in the vicinity of the lateral edge of the synapse. Thus, TNIK is
      highly enriched at a microdomain critical for glutamatergic signaling.

PMID- 25753358
TI  - Assessment of psychosocial problems in children with type 1 diabetes and their
      families: the added value of using standardised questionnaires in addition to
      clinical estimations of nurses and paediatricians.
AB  - AIMS AND OBJECTIVES: To investigate the assessment of psychosocial problems in
      children with type 1 diabetes by means of clinical estimations made by nurses and
      paediatricians and by using standardised questionnaires. BACKGROUND: Although
      children with type 1 diabetes and their parents show increased risk for
      psychosocial problems, standardised assessment of these problems lacks in
      diabetes care. DESIGN: By comparing these different modes of assessment, using a
      cross-sectional design, information about the additional value of using
      standardised questionnaires is provided. METHODS: Participants were 110 children
      with type 1 diabetes (aged 4-16), their parents, and healthcare professionals.
      Children filled out the Strengths and Difficulties Questionnaire and the
      Paediatric Quality of Life Inventory, Diabetes Module. Parents filled out the
      Strengths and Difficulties Questionnaire parent-report and the Parenting Stress
      Index. Independently, nurses and paediatricians filled out a short questionnaire,
      which assessed their clinical estimations of the children's psychosocial problems
      and quality of life, and parents' levels of parenting stress. Reports of children
      and parents were compared to clinical estimations. RESULTS: Children in our
      sample showed more psychosocial problems and lower health-related quality of life
      than their healthy peers. In approximately half of the children, dichotomous
      estimations by healthcare professionals and dichotomised reports by patients and
      parents were in agreement. In 10% of the children, no psychosocial problems were
      present according to professionals' estimations, although patients and parents
      reported psychosocial problems. In 40%, psychosocial problems were present
      according to professionals' estimations, although parents and patients did not
      report psychosocial problems. CONCLUSION: Children with type 1 diabetes show more
      psychosocial problems than healthy children. Professionals seem to tend towards
      overestimating psychosocial problems. RELEVANCE TO CLINICAL PRACTICE: Extending
      the assessment of psychosocial problems with routine screening on patient
      reported outcomes, using validated questionnaires, could be of additional value
      in tailoring care to the needs of the individual child and parents.

PMID- 25753359
TI  - Smoking and Gambling Disorder: Does Tobacco Use Influence Treatment Outcome?
AB  - The purpose of this study was to verify whether tobacco use influenced treatment
      outcome in a population of treatment seeking individuals with gambling disorder.
      Gambling disorder is defined as persistent and maladaptive gambling behaviour
      which meets four or more outlined criteria in the DSM-5. Tobacco use is the most
      frequent comorbidity with gambling disorder. A total of 676 treatment seeking
      individuals with gambling disorder were assessed at the National Problem Gambling
      Clinic in London. We analysed differences in socio-demographic, clinical and
      gambling variables between smokers and non-smokers and the relation between
      smoking behaviour and treatment completion and outcome. 46.4% (314) of our sample
      were daily tobacco users and were significantly younger, less likely to be in a
      stable relationship, more likely to be unemployed and have a lower education
      level. They were also significantly more likely to score higher on the AUDIT-C
      score and were significantly more likely to have used drugs in the last 30 days.
      There was no significant difference in PGSI score between smokers and non
      smokers. We found that tobacco smokers did not have higher PGSI scores than non
      smokers. Moreover, there was no significant difference between tobacco users and
      nonusers in terms of treatment completion and treatment outcome.

PMID- 25753360
TI  - Anonymisation of address coordinates for microlevel analyses of the built
      environment: a simulation study.
AB  - BACKGROUND: Data privacy is a major concern in spatial epidemiology because exact
      residential locations or parts of participants' addresses such as street or zip
      codes are used to perform geospatial analyses. To overcome this concern,
      different levels of aggregation such as census districts or zip code areas are
      mainly used, though any spatial aggregation leads to a loss of spatial
      variability. For the assessment of urban opportunities for physical activity that
      was conducted in the IDEFICS (Identification and prevention of dietary- and
      lifestyle-induced health effects in children and infants) study, macrolevel
      analyses were performed, but the use of exact residential addresses for micro
      level analyses was not permitted by the responsible office for data protection.
      We therefore implemented a spatial blurring to anonymise address coordinates
      depending on the underlying population density. METHODS: We added a standard
      Gaussian distributed error to individual address coordinates with the variance
      sigma2 depending on the population density and on the chosen k-anonymity. 1000
      random point locations were generated and repeatedly blurred 100 times to obtain
      anonymised locations. For each location 1 km network-dependent neighbourhoods
      were used to calculate walkability indices. Indices of blurred locations were
      compared to indices based on their sampling origins to determine the effect of
      spatial blurring on the assessment of the built environment. RESULTS: Spatial
      blurring decreased with increasing population density. Similarly, mean
      differences in walkability indices also decreased with increasing population
      density. In particular for densely-populated areas with at least 1500 residents
      per km2, differences between blurred locations and their sampling origins were
      small and did not affect the assessment of the built environment after spatial
      blurring. CONCLUSIONS: This approach allowed the investigation of the built
      environment at a microlevel using individual network-dependent neighbourhoods,
      while ensuring data protection requirements. Minor influence of spatial blurring
      on the assessment of walkability was found that slightly affected the assessment
      of the built environment in sparsely-populated areas.

PMID- 25753361
TI  - Regorafenib assessment in refractory advanced colorectal cancer: RegARd-C study
      protocol.
AB  - INTRODUCTION: Regorafenib was recently approved for patients with pretreated
      advanced colorectal cancer (aCRC), despite a moderate improvement of the
      patients' outcome, and significant toxicities. Based on previous studies showing
      that early fluorodeoxyglucose-positron emission tomography (FDG-PET)-based
      metabolic response assessment (MRA) might adequately select patients unlikely to
      benefit from treatment, the RegARd-C trial uses early MRA to identify likely non
      responders to regorafenib in a population of patients with aCRC and guide a
      comprehensive evaluation of genomic and epigenetic determinants of resistance to
      treatment. METHODS AND ANALYSIS: RegARd-C is a multicentric prospective study.
      Its primary objective is to identify non-benefitters from regorafenib given at
      160 mg/day, 3 weeks out of 4 in a population of patients with pretreated aCRC.
      Baseline PET is repeated at day 14 of the first treatment course. MRA is blinded
      for the investigators. Overall survival (OS) is the primary end point and will be
      correlated with metabolic parameters and (epi)genetic alterations assessed from
      tumour and serial blood samples. A target sample size of 105 evaluable patients
      (70 as derivation set and 35 as validation set), is considered as sufficient to
      validate an expected HR for OS of metabolic responders compared to metabolic non
      responders significantly <1 (with 80% power and 1-sided 5% alpha in case of a
      true HR<=0.59 and a responders rate of 47%). ETHICS AND DISSEMINATION: The study
      was approved by the Institut Jules Bordet's competent ethics committee and
      complies with the Helsinki declaration or the Belgian laws and regulations,
      whichever provides the greatest protection for the patient, and follows the
      International Conference on Harmonisation E 6 (R1) Guideline for Good Clinical
      Practice, reference number CPMP/ICH/135/95. The protocol and the trials results,
      even inconclusive, will be presented at international oncology congresses, and
      published in peer-reviewed journals. Genomic and epigenetic data will be made
      available in public open data sets. TRIAL REGISTRATION NUMBERS: EudraCT number:
      2012-005655-16; ClinicalTrials.gov number: NCT01929616.

PMID- 25753364
TI  - Visible light mediated sp(3) C-H bond functionalization of N-aryl-1,2,3,4
      tetrahydroisoquinolines via Ugi-type three-component reaction.
AB  - An efficient and high yield process for sp(3) C-H bond functionalization of N
      aryl-1,2,3,4-tetrahydroisoquinolines is disclosed. This involves a visible light
      mediated photoredox Ugi-type reaction with carboxylic acids and isonitriles under
      aerobic conditions, employing Ru(bpy)3Cl2 as a photoredox catalyst and CH3CN as
      the solvent. CH3CN was found to be crucial for the process, and good to excellent
      yields were achieved for a wide variety of N-aryl-1,2,3,4
      tetrahydroisoquinolines, carboxylic acids, and isonitriles. The developed
      methodology is attractive for the synthesis of a library of 1,2,3,4
      tetrahydroisoquinolines. 

PMID- 25753362
TI  - Protocol for the PREHAB study-Pre-operative Rehabilitation for reduction of
      Hospitalization After coronary Bypass and valvular surgery: a randomised
      controlled trial.
AB  - INTRODUCTION: Frailty is a geriatric syndrome characterised by reductions in
      muscle mass, strength, endurance and activity level. The frailty syndrome,
      prevalent in 25-50% of patients undergoing cardiac surgery, is associated with
      increased rates of mortality and major morbidity as well as function decline
      postoperatively. This trial will compare a preoperative, interdisciplinary
      exercise and health promotion intervention to current standard of care (StanC)
      for elective coronary artery bypass and valvular surgery patients for the purpose
      of determining if the intervention improves 3-month and 12-month clinical
      outcomes among a population of frail patients waiting for elective cardiac
      surgery. METHODS AND ANALYSIS: This is a multicentre, randomised, open end point,
      controlled trial using assessor blinding and intent-to-treat analysis. Two
      hundred and forty-four elective cardiac surgical patients will be recruited and
      randomised to receive either StanC or StanC plus an 8-week exercise and education
      intervention at a certified medical fitness facility. Patients will attend two
      weekly sessions and aerobic exercise will be prescribed at 40-60% of heart rate
      reserve. Data collection will occur at baseline, 1-2 weeks preoperatively, and at
      3 and 12 months postoperatively. The primary outcome of the trial will be the
      proportion of patients requiring a hospital length of stay greater than 7 days.
      POTENTIAL IMPACT OF STUDY: The healthcare team is faced with an increasingly
      complex older adult patient population. As such, this trial aims to provide novel
      evidence supporting a health intervention to ensure that frail, older adult
      patients thrive after undergoing cardiac surgery. ETHICS AND DISSEMINATION: Trial
      results will be published in peer-reviewed journals, and presented at national
      and international scientific meetings. The University of Manitoba Health Research
      Ethics Board has approved the study protocol V.1.3, dated 11 August 2014
      (H2014:208). TRIAL REGISTRATION NUMBER: The trial has been registered on
      ClinicalTrials.gov, a registry and results database of privately and publicly
      funded clinical studies (NCT02219815).

PMID- 25753363
TI  - Osteoblast differentiation profiles define sex specific gene expression patterns
      in craniosynostosis.
AB  - Single suture craniosynostosis (SSC) is the premature fusion of one calvarial
      suture and occurs in 1-1700-2500 live births. Congenital fusion of either the
      sagittal, metopic, or coronal sutures represents 95% of all cases of SSC.
      Sagittal and metopic synostosis have a male preponderance (3:1) while premature
      fusion of the coronal suture has a female preponderance (2:1). Although
      environmental and genetic factors contribute to SSC, the etiology of the majority
      of SSC cases remains unclear. In this study, 227 primary calvarial osteoblast
      cell lines from patients with coronal, metopic, or sagittal synostosis and
      unaffected controls were established and assayed for ALP activity and BrdU
      incorporation (n = 226) as respective measures of early stage osteoblast
      differentiation and proliferation. Primary osteoblast cell lines from individuals
      with sagittal synostosis demonstrated higher levels of ALP activity and reduced
      proliferation when compared to control lines. In order to address the sex
      differences in SSC types, the data was further stratified by sex. Osteoblasts
      from males and females with sagittal synostosis as well as males with metopic
      synostosis demonstrated higher levels of ALP activity when compared to sex
      matched controls, and males with sagittal or metopic synostosis demonstrated
      reduced levels of proliferation. In order to elucidate genes and pathways
      involved in these observed phenotypes, correlation analyses comparing ALP
      activity and proliferation to global gene expression was performed. Transcripts
      related to osteoblast differentiation were identified both differentially up and
      downregulated, correlated with ALP activity when compared to controls, and
      demonstrated a striking sex specific gene expression pattern. These data support
      that the dysregulation of osteoblast differentiation plays a role in the
      development of SSC and that genetic factors contribute to the observed sex
      related differences.

PMID- 25753365
TI  - Scalable 3D bicontinuous fluid networks: polymer heat exchangers toward
      artificial organs.
AB  - A scalable method for fabricating architected materials well-suited for heat and
      mass exchange is presented. These materials exhibit unprecedented combinations of
      small hydraulic diameters (13.0-0.09 mm) and large hydraulic-diameter-to
      thickness ratios (5.0-30,100). This process expands the range of material
      architectures achievable starting from photopolymer waveguide lattices or
      additive manufacturing. 

PMID- 25753367
TI  - 'Recognized, Valued and Supported'? The Experiences of Adult Siblings of People
      with Autism Plus Learning Disability.
AB  - BACKGROUND: The potential of adult siblings to offer long-term support to a
      brother or sister with autism is rarely realized. To understand this, our study
      explores the expectations of social care among adult siblings. METHOD: Using
      qualitative interviews, we spoke to 21 adult siblings about their family
      relationships and engagement with service delivery, met with 12 of their siblings
      with autism and talked to 12 social care staff. RESULTS: Siblings, although
      reflecting on the difficulties of growing up with someone who had autism,
      expressed a commitment towards their brother or sister. Most wanted involvement
      in their care. While some siblings described positive relationships with
      services, many felt marginalized. Practitioners largely confirmed their
      perceptions, while offering a justification for why they struggled to engage with
      adult siblings. CONCLUSION: By understanding the way relationships between
      siblings change over time, adult siblings' contribution to the lives of their
      disabled brother or sister can be better supported.

PMID- 25753366
TI  - Cobalt-catalysed site-selective intra- and intermolecular dehydrogenative
      amination of unactivated sp(3) carbons.
AB  - Cobalt-catalysed sp(2) C-H bond functionalization has attracted considerable
      attention in recent years because of the low cost of cobalt complexes and
      interesting modes of action in the process. In comparison, much less efforts have
      been devoted to the sp(3) carbons. Here we report the cobalt-catalysed site
      selective dehydrogenative cyclization of aliphatic amides via a C-H bond
      functionalization process on unactivated sp(3) carbons with the assistance of a
      bidentate directing group. This method provides a straightforward synthesis of
      monocyclic and spiro beta- or gamma-lactams with good to excellent
      stereoselectivity and functional group tolerance. In addition, a new procedure
      has been developed to selectively remove the directing group, which enables the
      synthesis of free beta- or gamma-lactam compounds. Furthermore, the first cobalt
      catalysed intermolecular dehydrogenative amination of unactivated sp(3) carbons
      is also realized. 

PMID- 25753368
TI  - Focused ultrasound transducer for thermal treatment.
AB  - Air-backed transducers have been employed for thermal ultrasonic treatment
      including both ablation and hyperthermia because the power efficiency rather than
      the bandwidth is a main concern, unlike a typical imaging transducer working in a
      pulse mode. The characteristic of an air-backed piezoelectric transducer with a
      matching layer is analysed, and the role and choice of the matching layer is
      discussed. An element size of a focused array transducer, appropriate for such
      thermal treatment, is then estimated, and the characteristic of a piezoceramic
      transducer element of such a size was numerically analysed using a finite element
      code. The characteristic of a piezocomposite transducer element is also
      numerically analysed and its suitability to such a therapeutic array transducer
      is discussed. 

PMID- 25753370
TI  - Spatio-temporal quantitative thermography of pre-focal interactions between high
      intensity focused ultrasound and the rib cage.
AB  - OBJECTIVE: The aim of this paper is to quantitatively investigate the thermal
      effects generated by the pre-focal interactions of a HIFU beam with a rib cage,
      in the context of minimally invasive transcostal therapy of liver malignancies.
      MATERIALS AND METHODS: HIFU sonications were produced by a phased-array MR
      compatible transducer on Turkey muscle placed on a sheep thoracic cage specimen.
      The thoracic wall was positioned in the pre-focal zone 3.5 to 6.5 cm below the
      focus. Thermal monitoring was simultaneously performed using fluoroptic sensors
      inserted into the medullar cavity of the ribs and high resolution MR-thermometry
      (voxel: 1 * 1 * 5 mm3, four multi-planar slices). RESULTS: MR-thermometry data
      indicated nearly isotropic distribution of the thermal energy at the ribs'
      surface. The temperature elevation at the focus was comparable with the
      pericostal temperature elevation around unprotected ribs, while being
      systematically inferior, by more than a factor of four on average, to the intra
      medullar values. The spatial profiles of the pericostal and intra-medullar
      thermal build-up measurements could be smoothly connected using a Gaussian
      function. The dynamics of the post-sonication thermal relaxation as determined by
      fluoroptic measurements was demonstrated to be theoretically coherent with the
      experimental observations. CONCLUSION: The experimental findings motivate further
      efforts for the transfer towards clinical routine of effective rib-sparing
      strategies for hepatic HIFU.

PMID- 25753369
TI  - Thermometry and ablation monitoring with ultrasound.
AB  - In this review we present the current status of ultrasound thermometry and
      ablation monitoring, with emphasis on the diverse approaches published in the
      literature and with an eye on which methods are closest to clinical reality. It
      is hoped that this review will serve as a guide to the expansion of sonographic
      methods for treatment monitoring and thermometry since the last brief review in
      2007. 

PMID- 25753372
TI  - Current status of randomized controlled trials for laparoscopic gastric surgery
      for gastric cancer in Korea.
AB  - Laparoscopic gastrectomy for gastric cancer has rapidly gained popularity as a
      result of the increased incidence of early gastric cancer in Korea. Although
      laparoscopic gastrectomy has been considered as an investigational treatment
      because of the lack of solid evidence of efficacy and safety, it is increasingly
      regarded as a standard treatment for early gastric cancer. Moreover, solid
      evidence is anticipated from two studies in Korea, KLASS 01 and KLASS 02, the
      latter of which examines the suitability of laparoscopic gastrectomy for advanced
      gastric cancer. The use of cutting-edge techniques for laparoscopic gastrectomy
      enables surgeons to deliver various treatment options that offer the best
      possible quality of life after gastrectomy. In this review, we summarize the
      current status of clinical trials on laparoscopic gastrectomy in Korea and
      examine future perspectives regarding laparoscopic gastrectomy for the treatment
      of gastric cancer. 

PMID- 25753371
TI  - Multidrug and toxin extrusion 1 and human organic cation transporter 1
      polymorphisms in patients with castration-resistant prostate cancer receiving
      metformin (SAKK 08/09).
AB  - BACKGROUND: This study was initiated to explore the impact of organic cation
      transporter 1 (OCT1) and multidrug and toxin extrusion transporter 1 (MATE1)
      genetic polymorphisms on toxicity, and clinical activity of metformin in patients
      with castration-resistant prostate cancer (CRPC). METHODS: The SAKK 08/09 trial
      included 44 patients with CRPC to receive single-agent metformin 1000 mg two
      times a day until disease progression or unwanted toxicity. Drug pathway
      associated gene polymorphisms of OCT1 (rs622342) and MATE1 (rs2289669) were
      assessed. The primary objective of this study was to define the relationship
      between mutations in OCT1, MATE1 and progression-free survival (PFS) at 12 weeks
      absolute PFS and PSA response in consenting patients of SAKK 08/09. The secondary
      objective of this study was to analyze the association between mutations in OCT1,
      MATE1, metformin-related toxicity, PSA response at 12 weeks and overall survival.
      RESULTS: Thirty-six patients were evaluable for pharmacogenetic analysis.
      Homozygous carriers of the polymorphic OCT1 C-allele had no metformin-related
      toxicity as compared with 41.9% for any metformin-related toxicity in carriers of
      at least one wild-type A-allele (P=0.07). Disease progression according to RECIST
      (Response Evaluation Criteria In Solid Tumors) was significantly more frequent in
      homozygous carriers of the polymorphic OCT1 C-allele (80%) as compared with
      carriers of at least one wild-type A-allele (28.6%) (P=0.002). Disease
      progression according to RECIST was also more frequent in carriers of at least
      one polymorphic MATE1 A-allele (44%) as compared with homozygous carriers of the
      wild-type G-allele (12.5%) (P=0.07). OCT1 and MATE1 were not associated with PFS.
      CONCLUSIONS: The polymorphic OCT1 C-allele has been shown to be associated with
      less metformin-related toxicity and a higher risk of tumor progression in
      patients with CRPC receiving metformin as an anticancer treatment. Polymorphisms
      in metformin drug transporters are attractive molecular markers to serve as
      potential predictors of efficacy in future clinical studies.

PMID- 25753373
TI  - Morphometric measurement of submucosal thickness in areas of fat deposition in
      the terminal ileum and colonic sections, with correlation with body mass index,
      weight and age: a male autopsy study.
AB  - AIMS: An increased amount of submucosal (SM) fat in the colon on imaging is
      considered to be characteristic of inflammatory bowel disease (IBD); however, a
      recent study in patients without IBD reported a correlation between colonic SM
      fat deposition and body weight (BW). The aim of this study was to perform a
      morphometric investigation of SM thickness in areas of fat deposition in the
      terminal ileum (TI), ileocaecal valve (ICV), and colonic sections, to determine
      whether there are variations by site, and whether it shows a correlation with BW,
      body mass index (BMI), or age. METHODS AND RESULTS: Representative samples of TI,
      ICV and colonic sections were collected prospectively from 115 autopsy cases
      without IBD. All of the study subjects were male (Veterans Hospital). SM
      thickness was measured in areas of fat deposition. Correlation analysis was
      performed between SM thickness and BW, BMI, and age. Fat deposition was common;
      however, with the exception of the ICV, it was neither consistent nor prominent,
      and it did not show a statistical correlation with BW, BMI, or age. CONCLUSIONS:
      SM fat deposition is common but not uniform or conspicuous in the TI or colon. In
      contrast to extravisceral intra-abdominal fat, it does not show a correlation
      with BW or BMI, and is not associated with ageing. As all study subjects were
      male, gender-dependent variability cannot be excluded.

PMID- 25753374
TI  - Giant annular purpuric eruption as a unique clinical manifestation of skin
      metastasis in apocrine carcinoma.

PMID- 25753375
TI  - Transparent ALD-grown Ta2O5 protective layer for highly stable ZnO photoelectrode
      in solar water splitting.
AB  - This communication describes a highly stable ZnO/Ta2O5 photoanode with Ta2O5
      deposited by atomic layer deposition. The ultrathin Ta2O5 protective layer
      prevents corrosion of ZnO and reduces surface carrier recombination, leading to a
      nearly two-fold increase of photo-conversion efficiency. The transparency of
      Ta2O5 to sunlight is identified as the main reason for the excellent stability of
      the photoelectrode for 5 hours. 

PMID- 25753376
TI  - Modeling the IR spectra of aqueous metal carboxylate complexes: correlation
      between bonding geometry and stretching mode wavenumber shifts.
AB  - A widely used principle is that shifts in the wavenumber of carboxylate
      stretching modes upon bonding with a metal center can be used to infer if the
      geometry of the bonding is monodentate or bidentate. We have tested this
      principle with ab initio modeling for aqueous metal carboxylate complexes and
      have shown that it does indeed hold. Modeling of the bonding of acetate and
      formate in aqueous solution to a range of cations was used to predict the
      infrared spectra of the metal-carboxylate complexes, and the wavenumbers of the
      symmetric and antisymmetric vibrational modes are reported. Furthermore, we have
      shown that these shifts in wavenumber occur primarily due to how bonding with the
      metal changes the carboxylate C-O bond lengths and O-C-O angle.

PMID- 25753377
TI  - Protective effects of the angiotensin type 1 receptor antagonist losartan in
      infection-induced and arthritis-associated alveolar bone loss.
AB  - BACKGROUND AND OBJECTIVE: The angiotensin type 1 (AT1) receptor has been
      implicated in the pathogenesis of inflammatory bone disorders. This study aimed
      to investigate the effect of an AT1 receptor antagonist in infection-induced and
      arthritis-associated alveolar bone loss in mice. MATERIAL AND METHODS: Mice were
      subjected to Aggregatibacter actinomycetemcomitans oral infection or antigen
      induced arthritis and treated daily with 10 mg/kg of the prototype AT1
      antagonist, losartan. Treatment was conducted for 30 d in the infectious
      condition and for 17 d and 11 d in the preventive or therapeutic regimens in the
      arthritic model, respectively. The mice were then killed, and the maxillae, serum
      and knee joints were collected for histomorphometric and immunoenzymatic assays.
      In vitro osteoclast assays were performed using RAW 264.7 cells stimulated with
      A. actinomycetemcomitans lipopolysacharide (LPS). RESULTS: Arthritis and A.
      actinomycetemcomitans infection triggered significant alveolar bone loss in mice
      and increased the levels of myeloperoxidase and of TRAP(+) osteoclasts in
      periodontal tissues. Losartan abolished such a phenotype, as well as the
      arthritis joint inflammation. Both arthritis and A. actinomycetemcomitans
      conditions were associated with the release of tumor necrosis factor alpha (TNF
      alpha), interferon-gamma, interleukin-17 and chemokine (C-X-C motif) ligand 1 and
      an increased RANKL/osteoprotegerin ratio in periodontal tissues, but such
      expression decreased after losartan treatment, except for TNF-alpha. The
      therapeutic approach was as beneficial as the preventive one. In vitro, losartan
      prevented LPS-induced osteoclast differentiation and activity. CONCLUSION: The
      blockade of AT1 receptor exerts anti-inflammatory and anti-osteoclastic effects,
      thus protecting periodontal tissues in distinct pathophysiological conditions of
      alveolar bone loss.

PMID- 25753378
TI  - The role of gamma delta T cells in haematopoietic stem cell transplantation.
AB  - Although haematopoietic stem cell transplantation (HSCT) is a potential curative
      treatment for haematological malignancies, it is still a procedure associated
      with substantial morbidity and mortality due to toxicity, graft-versus-host
      disease (GVHD) and relapse. Recent attempts of developing safer transplantation
      modalities increasingly focuses on selective cell depletion and graft engineering
      with the aim of retaining beneficial immune donor cells for the graft-versus
      leukaemia (GVL) effect. In this context, the adoptive and especially innate
      effector functions of gammadelta T cells together with clinical studies
      investigating the effect of gammadelta T cells in relation to HSCT are reviewed.
      In addition to phospho-antigen recognition by the gammadelta T cell receptor
      (TCR), gammadelta T cells express receptors of the natural killer (NK) and
      natural cytotoxicity (NCR) families enabling them to recognize and kill leukaemia
      cells. Antigen recognition independent from the major histocompatibility complex
      (MHC) allows for the theoretical possibility of mediating GVL without an
      allogeneic response in terms of GVHD. Early studies on the impact of gammadelta T
      cells in HSCT have reported conflicting results. Recent studies, however, do
      suggest an overall favourable effect of high gammadelta T cell immune
      reconstitution after HSCT; patients with elevated numbers of gammadelta T cells
      had a significantly higher overall survival rate and a decreased rate of acute
      GVHD compared to patients with low or normal gammadelta T cell counts. Further
      research in terms of effector mechanisms, subtypes and tissue distribution during
      the course of HSCT is needed to assess the potentially beneficial effects of
      gammadelta T cells in this setting. 

PMID- 25753379
TI  - Genomic signatures of geographic isolation and natural selection in coral reef
      fishes.
AB  - The drivers of speciation remain among the most controversial topics in
      evolutionary biology. Initially, Darwin emphasized natural selection as a primary
      mechanism of speciation, but the architects of the modern synthesis largely
      abandoned that view in favour of divergence by geographic isolation. The balance
      between selection and isolation is still at the forefront of the evolutionary
      debate, especially for the world's tropical oceans where biodiversity is high,
      but isolating barriers are few. Here, we identify the drivers of speciation in
      Pacific reef fishes of the genus Acanthurus by comparative genome scans of two
      peripheral populations that split from a large Central-West Pacific lineage at
      roughly the same time. Mitochondrial sequences indicate that populations in the
      Hawaiian Archipelago and the Marquesas Islands became isolated approximately 0.5
      Ma. The Hawaiian lineage is morphologically indistinguishable from the widespread
      Pacific form, but the Marquesan form is recognized as a distinct species that
      occupies an unusual tropical ecosystem characterized by upwelling, turbidity,
      temperature fluctuations, algal blooms and little coral cover. An analysis of
      3737 SNPs reveals a strong signal of selection at the Marquesas, with 59 loci
      under disruptive selection including an opsin Rh2 locus. While both the Hawaiian
      and Marquesan populations indicate signals of drift, the former shows a weak
      signal of selection that is comparable with populations in the Central-West
      Pacific. This contrast between closely related lineages reveals one population
      diverging due primarily to geographic isolation and genetic drift, and the other
      achieving taxonomic species status under the influence of selection.

PMID- 25753380
TI  - Gastric mucosa-associated lymphoid tissue lymphoma masquerading as Russell body
      gastritis.

PMID- 25753382
TI  - Immunohistochemical analysis on MMP-2 and MMP-9 for wound age determination.
AB  - We performed immunohistochemical study combined with morphometrical analyses in
      order to examine the expression of matrix metalloproteinase-2 (MMP-2) and MMP-9
      using 55 human skin wounds of different ages: group I, 0-3 days (n = 16); II, 4-7
      days (n = 11); III, 9-14 days (n = 16); and IV, 17-21 days (n = 12).
      Immunopositive reactions for MMP-2 were observed in all human skin specimens
      including uninjured skin as control. The number of MMP-2(+) macrophages was
      significantly increased in accordance with wound ages. In contrast to MMP-2, no
      MMP-9(+) signals were detected in uninjured and wound specimens aged less than 1
      day. However, the number of MMP-9(+) macrophages profoundly appeared in groups II
      and III. Morphometrically, in all of wound samples aged 9-12 days, MMP-2(+) cell
      number was more than 20. On the contrary, most of the remaining samples had <20
      positive cells. However, only one sample (a 7-day-old wound) showed 21 positive
      cells. Thus, with regard to practical applicability with forensic safety, MMP
      2(+) macrophages of >20 would indicate a wound age of 7-12 days. Additionally, 10
      out of 12 wound specimens aged 9-12 days showed the MMP-2(+) cell number of >25,
      implying that MMP-2(+) cell number of >25 would indicate the wound age of 9-12
      days. On the contrary, all wound samples aged 3-14 days except for only one
      sample had MMP-9(+) cell number of >30, indicating that MMP-9(+) cell number of
      >30 would indicate the wound age of 3-14 days. Collectively, MMP-2 seemed to be
      more distinct marker, compared with MMP-9.

PMID- 25753381
TI  - The T cell antigen receptor: the Swiss army knife of the immune system.
AB  - The mammalian T cell receptor (TCR) orchestrates immunity by responding to many
      billions of different ligands that it has never encountered before and cannot
      adapt to at the protein sequence level. This remarkable receptor exists in two
      main heterodimeric isoforms: alphabeta TCR and gammadelta TCR. The alphabeta TCR
      is expressed on the majority of peripheral T cells. Most alphabeta T cells
      recognize peptides, derived from degraded proteins, presented at the cell surface
      in molecular cradles called major histocompatibility complex (MHC) molecules.
      Recent reports have described other alphabeta T cell subsets. These
      'unconventional' T cells bear TCRs that are capable of recognizing lipid ligands
      presented in the context of the MHC-like CD1 protein family or bacterial
      metabolites bound to the MHC-related protein 1 (MR1). gammadelta T cells
      constitute a minority of the T cell pool in human blood, but can represent up to
      half of total T cells in tissues such as the gut and skin. The identity of the
      preferred ligands for gammadelta T cells remains obscure, but it is now known
      that this receptor can also functionally engage CD1-lipid, or immunoglobulin (Ig)
      superfamily proteins called butyrophilins in the presence of pyrophosphate
      intermediates of bacterial lipid biosynthesis. Interactions between TCRs and
      these ligands allow the host to discriminate between self and non-self and co
      ordinate an attack on the latter. Here, we describe how cells of the T lymphocyte
      lineage and their antigen receptors are generated and discuss the various modes
      of antigen recognition by these extraordinarily versatile receptors. 

PMID- 25753383
TI  - Autophagy in skin wounds: a novel marker for vital reactions.
AB  - Detection of vitality of mechanical wounds in human cadavers is one of the
      important issues in forensic medicine. In order to explore novel markers for
      vitality of acute mechanical wounds, we investigated autophagy in mouse and human
      skin wounds. Western blotting analysis of mouse skin wounds showed marked
      reduction of LC3-II and reciprocal increase of p62 in wound samples with the
      postinfliction intervals of >=0.5 h, compared with the uninjured skin tissues.
      These observations indicated that autophagy level was reduced in the wound sites.
      In postmortem wound samples, there were no remarkable changes in LC3-II and p62
      levels. Furthermore, the postmortem intervals of 1-4 days have no significant
      effects on the changes of LC3-II and p62 in the antemortem skin wounds. Like
      murine wound samples, these alterations of LC3-II and p62 could be detected in
      human skin wound samples. Collectively, our study using animal and human samples
      implied that the detection of autophagy-related molecules such as LC3-II and p62
      might be useful for forensic practice as markers of wound vitality.

PMID- 25753384
TI  - Traumatic asphyxia--fatal accident in an automatic revolving door.
AB  - Due to continuing modernisation, the number of automatic doors in routine use,
      including powered revolving doors, has increased in recent years. Automatic
      revolving doors are found mostly in department stores, airports, railway stations
      and hospitals. Although safety arrangements and guidelines concerning the
      installation of automatic doors are in existence, their disregard in conjunction
      with obsolete or incorrect installation can lead to fatal accidents. In this
      report, a 19-month-old boy is described whose right arm was caught between the
      elements of an automatic revolving door. As a direct result of rescue attempts,
      the child's body was drawn further into the narrow gap between elements of the
      door. To get the boy's body out of the 4-cm-wide gap between the fixed outer wall
      of the revolving door and the revolving inner, back-up batteries had to be
      disconnected so as to stop the electrical motor powering the door.
      Cardiopulmonary resuscitation was begun immediately after the rescue but was
      unsuccessful; the child was declared dead at the hospital he was taken to. The
      cause of death was a combination of compression-related skull and brain injury
      together with thoracic compression. This case shows an outstanding example of the
      preventive aspect as a special task of forensic medicine. Additionally, it serves
      as a warning for the correct installation and use of automatic revolving doors.
      Even so, small children should not use these doors on their own, but only with an
      alert companion, so as to prevent further fatal accidents of this sort. 

PMID- 25753387
TI  - The Journey.

PMID- 25753385
TI  - Free-breathing, motion-corrected, highly efficient whole heart T2 mapping at 3T
      with hybrid radial-cartesian trajectory.
AB  - PURPOSE: To develop and test a time-efficient, free-breathing, whole heart T2
      mapping technique at 3.0T. METHODS: ECG-triggered three-dimensional (3D) images
      were acquired with different T2 preparations at 3.0T during free breathing.
      Respiratory motion was corrected with a navigator-guided motion correction
      framework at near perfect efficiency. Image intensities were fit to a
      monoexponential function to derive myocardial T2 maps. The proposed 3D, free
      breathing, motion-corrected (3D-FB-MoCo) approach was studied in ex vivo canine
      hearts and kidneys, healthy volunteers, and canine subjects with acute myocardial
      infarction (AMI). RESULTS: Ex vivo T2 values from proposed 3D T2 -prep gradient
      echo were not different from two-dimensional (2D) spin echo (P = 0.7) and T2 
      prep balanced steady-state free precession (bSSFP) (P = 0.7). In healthy
      volunteers, compared with 3D-FB-MoCo and breath-held 2D T2 -prep bSSFP (2D-BH),
      non-motion-corrected (3D-FB-Non-MoCo) myocardial T2 was longer, had a larger
      coefficient of variation (COV), and had a lower image quality (IQ) score (T2 =
      40.3 ms, COV = 38%, and IQ = 2.3; all P < 0.05). Conversely, the mean and COV and
      IQ of 3D-FB-MoCo (T2 = 37.7 ms, COV = 17%, and IQ = 3.5) and 2D-BH (T2 = 38.0 ms,
      COV = 15%, and IQ = 3.8) were not different (P = 0.99, P = 0.74, and P = 0.14,
      respectively). In AMI, T2 values and edema volumes from 3D-FB-MoCo and 2D-BH were
      closely correlated (R(2) = 0.88 and 0.96, respectively). CONCLUSION: The proposed
      whole heart T2 mapping approach can be performed within 5 min with similar
      accuracy to that of the 2D-BH T2 mapping approach.

PMID- 25753386
TI  - Medical Students' Views and Knowledge of the Affordable Care Act: A Survey of
      Eight U.S. Medical Schools.
AB  - BACKGROUND: It is not known whether medical students support the Affordable Care
      Act (ACA) or possess the knowledge or will to engage in its implementation as
      part of their professional obligations. OBJECTIVE: To characterize medical
      students' views and knowledge of the ACA and to assess correlates of these views.
      DESIGN: Cross-sectional email survey. PARTICIPANTS: All 5,340 medical students
      enrolled at eight geographically diverse U.S. medical schools (overall response
      rate 52% [2,761/5,340]). MAIN MEASURES: Level of agreement with four questions
      regarding views of the ACA and responses to nine knowledge-based questions. KEY
      RESULTS: The majority of respondents indicated an understanding of (75.3%) and
      support for (62.8%) the ACA and a professional obligation to assist with its
      implementation (56.1%). The mean knowledge score from nine knowledge-based
      questions was 6.9 +/- 1.3. Students anticipating a surgical specialty or
      procedural specialty compared to those anticipating a medical specialty were less
      likely to support the legislation (OR = 0.6 [0.4-0.7], OR = 0.4 [0.3-0.6],
      respectively), less likely to indicate a professional obligation to implement the
      ACA (OR = 0.7 [0.6-0.9], OR = 0.7 [0.5-0.96], respectively), and more likely to
      have negative expectations (OR = 1.9 [1.5-2.6], OR = 2.3 [1.6-3.5],
      respectively). Moderates, liberals, and those with an above-average knowledge
      score were more likely to indicate support for the ACA (OR = 5.7 [4.1-7.9], OR =
      35.1 [25.4-48.5], OR = 1.7 [1.4-2.1], respectively) and a professional obligation
      toward its implementation (OR = 1.9 [1.4-2.5], OR = 4.7 [3.6-6.0], OR = 1.2 [1.02
      1.5], respectively). CONCLUSIONS: The majority of students in our sample support
      the ACA. Support was highest among students who anticipate a medical specialty,
      self-identify as political moderates or liberals, and have an above-average
      knowledge score. Support of the ACA by future physicians suggests that they are
      willing to engage with health care reform measures that increase access to care.

PMID- 25753388
TI  - Basal cell carcinoma with an epidermal collarette: A case report and review of
      published work.

PMID- 25753390
TI  - Reconciling Estimates of the Value to Firms of Reduced Regulatory Delay in the
      Marketing of Their New Drugs.
AB  - The prescription drug user fee program provides additional resources to the U.S.
      Food and Drug Administration at the expense of regulated firms. Those resources
      accelerate the review of new drugs. Faster approvals allow firms to realize
      profits sooner, and the program is supported politically by industry. However,
      published estimates of the value to firms of reduced regulatory delay vary
      dramatically. It is shown here that this variation is driven largely by
      differences in methods that correspond to differences in implicit assumptions
      about the effects of reduced delay. Theoretical modeling is used to derive an
      equation describing the relationship between estimates generated using different
      methods. The method likely to yield the most accurate results is identified. A
      reconciliation of published estimates yields a value to a firm for a one-year
      reduction in regulatory delay at the time of approval of about $60 million for a
      typical drug. Published 2015. This article is a U.S. Government work and is in
      the public domain in the U.S.A.

PMID- 25753389
TI  - A roadmap for interpreting the literature on vision and driving.
AB  - Over the past several decades there has been a sharp increase in the number of
      studies focused on the relationship between vision and driving. The intensified
      attention to this topic has most likely been stimulated by the lack of an
      evidence basis for determining vision standards for driving licensure and a poor
      understanding about how vision impairment impacts driver safety and performance.
      Clinicians depend on the literature on vision and driving to advise visually
      impaired patients appropriately about driving fitness. Policy makers also depend
      on the scientific literature in order to develop guidelines that are evidence
      based and are thus fair to persons who are visually impaired. Thus it is
      important for clinicians and policy makers alike to understand how various study
      designs and measurement methods should be interpreted so that the conclusions and
      recommendations they make are not overly broad, too narrowly constrained, or even
      misguided. We offer a methodological framework to guide interpretations of
      studies on vision and driving that can also serve as a heuristic for researchers
      in the area. Here, we discuss research designs and general measurement methods
      for the study of vision as they relate to driver safety, driver performance, and
      driver-centered (self-reported) outcomes. 

PMID- 25753391
TI  - The influence of the location and extent of intrauterine adhesions on recurrence
      after hysteroscopic adhesiolysis.
AB  - OBJECTIVE: To investigate the recurrence potential of intrauterine adhesions
      after hysteroscopic adhesiolysis. DESIGN: Retrospective observational study.
      SETTING: Tertiary university hospital. POPULATION: This study included 115 women
      who had intrauterine adhesions completely separated during hysteroscopic surgery.
      The treated adhesions were classified into four groups according to their
      location and extent: Group 1, central type (i.e. intervening space between the
      adhesions and both lateral uterine sidewalls) at the middle area of uterine
      cavity; Group 2, central type at uterine cornua; Group 3, cervico-isthmic; and
      Group 4, extensive if the adhesions were dense with occlusion of part of the
      uterine cavity other than cervico-isthmic region. METHODS: Postoperative
      outpatient hysteroscopic adhesiolysis was scheduled 10-14 days after the initial
      hysteroscopic surgery and procedures were repeated every 10-14 days until no
      reformed adhesions were detected. Multivariate logistic regression models were
      built to examine initial adhesion characteristics and other factors associated
      with adhesion reformation and need for subsequent outpatient adhesiolysis.
      Categorical data were compared using Fisher's exact test. MAIN OUTCOME MEASURES:
      Number of postoperative outpatient hysteroscopic adhesiolysis procedures.
      RESULTS: The location and extent of adhesions according to the allocated group
      was the only parameter independently related to the number of postoperative
      outpatient adhesiolysis procedures (P = 0.0004). Women with Group 1 adhesions
      underwent a lower number of postoperative interventions compared with those with
      Group 2, 3 and 4 adhesions (P = 0.0355, P = 0.0004 and P = 0.0087, respectively).
      CONCLUSIONS: There is an increased likelihood of intrauterine adhesion recurrence
      when successfully divided adhesions were originally located at the uterine
      cornua, the cervico-isthmic region or involved a large portion of the uterine
      cavity.

PMID- 25753392
TI  - The effects of an overnight holding of whole blood at room temperature on
      haemoglobin modification and in vitro markers of red blood cell aging.
AB  - BACKGROUND: Some effects of the red blood cell (RBC) storage lesion are well
      documented whereas others are not. Whether a period of room temperature hold
      (RTH) during RBC production enhances the RBC storage lesion has remained
      controversial. In this study, we compared whole blood (WB)-derived RBCs produced
      after 24-h RTH with rapidly cooled (RC) RBCs and tested them for classical
      metabolic markers and signs of oxidative damage. STUDY DESIGN AND METHODS: SAGM
      RBCs were prepared from mixed and split pairs (n = 12) of WB units. RBCs prepared
      after a 24-h period of RTH on day+1 after collection (RTH-RBCs) were compared
      with RC-RBCs. All RBCs were stored at 4 degrees C for 42 days with assay of in
      vitro variables on days+1, +15, +22, +29 and +42. The study examined standard
      quality parameters, glutathione, catalase and superoxide dismutase (SOD)
      activities, and indicative markers of oxidative cell damage including post
      translational haemoglobin modification, malondialdehyde (MDA), and
      phosphatidylserine expression. RESULTS: RTH-RBCs exhibited decreased levels of
      potassium (1.98 +/- 0.26 vs. 5.23 +/- 0.65 mmol/l) and of 2,3-diphosphoglycerate
      (2,3-DPG) on day+1 compared with RC-RBCs. Haemolysis rate on day+42 was higher in
      RTH-RBCs than in RC-RBCs (0.52 +/- 0.13 vs. 0.37 +/- 0.12%). The
      phosphatidylserine expression amounted to 0.25 +/- 0.20% in RTH-RBCs and 0.07 +/-
      0.12% in RC-RBCs. Haemoglobin modification was not different between both RBC
      groups. RTH-RBCs showed slightly higher MDA concentration on days +29 and +42.
      CONCLUSIONS: RC-RBCs and RTH-RBCs show only small differences of classical in
      vitro parameters and no relevant differences in antioxidative metabolism and
      oxidative haemoglobin modification. These findings do not explain the loss
      observed in in vivo survival studies with RBCs.

PMID- 25753393
TI  - p84 forms a negative regulatory complex with p110gamma to control PI3Kgamma
      signalling during cell migration.
AB  - Phosphoinositide 3-kinase gamma (PI3Kgamma) consists of the catalytic subunit
      p110gamma that forms a mutually exclusive heterodimer with one of the two adaptor
      subunits, p101 or p84. Although activation of PI3Kgamma is necessary for cell
      migration downstream of G-protein-coupled receptor engagement, particularly
      within the immune system, aberrant PI3Kgamma signalling has been associated with
      transformation, increased migration and the progression of multiple cancer types.
      Regulation of PI3Kgamma signal activation and duration is critical to controlling
      and maintaining coordinated cellular migration; however, the mechanistic basis
      for this is not well understood. We have recently demonstrated that, in contrast
      to the tumour-promoting potential of p110gamma and p101, p84 possesses tumour
      suppressor activity, suggesting a negative regulatory role within PI3Kgamma
      signalling. The present study investigated the role of p84 phosphorylation in the
      context of PI3Kgamma signalling, cell migration and p84-mediated tumour
      suppression. Two putative phosphorylation sites were characterised within p84,
      Ser358 and Thr607. Expression of wild-type p84 reduced the oncogenic potential of
      MDA.MB.231 cells and inhibited metastatic lung colonisation in vivo, effects that
      were dependent on Thr607. Furthermore, loss of Thr607 enhanced migration of
      MDA.MB.231 cells in vitro and prevented the induction of p84/p110gamma dimers.
      The dimerisation of wild-type p84 with p110gamma was not detected at the plasma
      membrane, indicating an inhibitory interaction preventing PI3Kgamma lipid-kinase
      activity. In contrast, Ser358 phosphorylation was not determined to be critical
      for p84 activity in the context of migration. Our findings suggest that p84
      binding to p110gamma may represent a novel negative feedback signal that
      terminates PI3Kgamma activity. 

PMID- 25753395
TI  - Biomass carbon, nitrogen and phosphorus stocks in hybrid poplar buffers,
      herbaceous buffers and natural woodlots in the riparian zone on agricultural
      land.
AB  - In many temperate agricultural areas, riparian forests have been converted to
      cultivated land, and only narrow strips of herbaceous vegetation now buffer many
      farm streams. The afforestation of these riparian zones has the potential to
      increase carbon (C) storage in agricultural landscapes by creating a new biomass
      sink for atmospheric CO2. Occurring at the same time, the storage of nitrogen (N)
      and phosphorus (P) in plant biomass, is an important water quality function that
      may greatly vary with types of riparian vegetation. The objectives of this study
      were (1) to compare C, N and P storage in aboveground, belowground and detrital
      biomass for three types of riparian vegetation cover (9-year-old hybrid poplar
      buffers, herbaceous buffers and natural woodlots) across four agricultural sites
      and (2) to determine potential vegetation cover effects on soil nutrient supply
      rate in the riparian zone. Site level comparisons suggest that 9-year-old poplar
      buffers have stored 9-31 times more biomass C, 4-10 times more biomass N, and 3-7
      times more biomass P than adjacent non managed herbaceous buffers, with the
      largest differences observed on the more fertile sites. The conversion of these
      herbaceous buffers to poplar buffers could respectively increase C, N and P
      storage in biomass by 3.2-11.9 t/ha/yr, 32-124 kg/ha/yr and 3.2-15.6 kg/ha/yr,
      over 9 years. Soil NO3 and P supply rates during the summer were respectively 57%
      and 66% lower in poplar buffers than in adjacent herbaceous buffers, potentially
      reflecting differences in nutrient storage and cycling between the two buffer
      types. Biomass C ranged 49-160 t/ha in woodlots, 33-110 t/ha in poplar buffers
      and 3-4 t/ha in herbaceous buffers. Similar biomass C stocks were found in the
      most productive poplar buffer and three of the four woodlots studied. Given their
      large and varied biomass C stocks, conservation of older riparian woodlots is
      equally important for C balance management in farmland. In addition, the
      establishment of poplar buffers, in replacement of non managed herbaceous
      buffers, could rapidly increase biomass C, N and P storage along farm streams,
      which would be beneficial for water quality protection and global change
      mitigation. 

PMID- 25753394
TI  - Trx1/TrxR1 system regulates post-selected DP thymocytes survival by modulating
      ASK1-JNK/p38 MAPK activities.
AB  - A key process in the development of T lymphocyte in the thymus is T-cell receptor
      (TCR) selection. It is controlled by complex signaling pathways that contain
      redox-sensitive molecules. However, the redox status early after TCR selection
      and how redox regulators promote the survival of post-selected DP thymocytes has
      not been directly addressed. The present study demonstrated that the transition
      from pre- to post-selected double-positive (DP) stages was accompanied with an
      increase of reactive oxygen species (ROS) and a transient surge in the expression
      of a variety of redox regulators. Among them, the thioredoxin (Trx)1/thioredoxin
      reductase (TrxR)1 system was found to be critically involved in the regulation of
      cell survival of DP thymocytes, especially that of post-selected CD69(+) subset,
      as its inhibition caused a specific reduction of these cells both in vitro and in
      vivo, most likely owing to increased apoptosis. Suppression of the glutathione
      dependent redox system, on the other hand, showed no obvious impact.
      Biochemically, treatment of DP thymcoytes with TrxR1 inhibitor alone or in
      conjunction with anti-CD3 resulted in enhanced phosphorylation of redox-sensitive
      ASK-1, JNK and p38 MAPK, and upregulated expression of Bim. Taken together, the
      data presented here suggest that the timely upregulation of Trx1/TrxR1 and the
      active control of intracellular redox status is critical for the survival of
      thymocytes during and short after positive selection. 

PMID- 25753396
TI  - Efficiency of an emissions payment system for nitrogen in sewage treatment plants
      - a case study.
AB  - An emissions payment system for nitrogen in Swedish sewage treatment plants
      (STPs) was evaluated using a semi-empirical approach. The system was based on a
      tariff levied on each unit of nitrogen emitted by STPs, and profitable measures
      to reduce nitrogen emissions were identified for twenty municipal STPs. This was
      done through direct involvement with the plant personnel and the results were
      scaled up to cover all treatment plants larger than 2000 person equivalents in
      the Swedish tributary areas of the Kattegat and the Baltic Proper. The sum of
      costs and nitrogen reductions were compared with an assumed command-and-control
      regulation requiring all STPs to obtain 80% total nitrogen reduction in their
      effluents. Costs for the latter case were estimated using a database containing
      standard estimates for reduction costs by six specified measures. For both cases
      a total reduction target of 3000 tonnes of nitrogen was set. We did not find that
      the emissions payment system was more efficient in terms of total reduction
      costs, although some practical and administrative advantages could be identified.
      Our results emphasize the need to evaluate the performance of policy instruments
      on a case-by-case basis since the theoretical efficiency is not always reflected
      in practice. 

PMID- 25753397
TI  - The impact of exogenous N supply on soluble organic nitrogen dynamics and
      nitrogen balance in a greenhouse vegetable system.
AB  - A long-term greenhouse experiment (2004-2012) was conducted with continuous
      tomato (Lycopersicum esculentum Mill.) plantings to understand the influence of
      an exogenous nitrogen supply from irrigation water, chemical fertilizer, or
      organic amendment on the N balance and soluble organic nitrogen (SON). The
      results from 16 tomato growing seasons indicated that the application of organic
      amendment (manure and straw) alone (Or-N) resulted in the same yield as the
      conventional chemical N with organic amendment (Co-N) and the reduced chemical N
      with organic amendment (Re-N) treatments. The annual apparent N loss was >1000
      and 438 kg N ha(-1) in the Co-N and Re-N treatments, respectively. Over the study
      period, the SON in the 1.8 m soil profile was 1449 and 1978 kg N ha(-1) in the Re
      N and Co-N treatments, respectively, it was 1.7- and 2.3-fold higher than that
      observed in the Or-N treatment, which indicated that SON increased with the
      chemical N application. The percentage of SON in the cumulative soluble N (SON
      plus mineral N) ranged from 28% to 44%, and there were no significant differences
      across the 0-0.6, 0.6-1.2, and 1.2-1.8 m soil profile, which indicated that the
      leaching and distribution of SON was similar to those of the mineral N in the 0
      1.8 m soil profile. We conclude that the mobility of soluble organic N in the 0
      1.8 m of the soil was synchronous with the mineral N under a greenhouse
      production system, and the risk of soluble organic N leaching increased with
      inorganic N application rate. Therefore, leaching of SON in the intensive
      agriculture should not be ignored when evaluating the risk of N leaching.

PMID- 25753398
TI  - Continuous non-cell autonomous reprogramming to generate retinal ganglion cells
      for glaucomatous neuropathy.
AB  - Glaucoma, where the retinal ganglion cells (RGCs) carrying the visual signals
      from the retina to the visual centers in the brain are progressively lost, is the
      most common cause of irreversible blindness. The management approaches, whether
      surgical, pharmacological, or neuroprotective do not reverse the degenerative
      changes. The stem cell approach to replace dead RGCs is a viable option but
      currently faces several barriers, such as the lack of a renewable, safe, and
      ethical source of RGCs that are functional and could establish contacts with bona
      fide targets. To address these barriers, we have derived RGCs from the easily
      accessible adult limbal cells, reprogrammed to pluripotency by a non-nucleic acid
      approach, thus circumventing the risk of insertional mutagenesis. The generation
      of RGCs from the induced pluripotent stem (iPS) cells, also accomplished non-cell
      autonomously, recapitulated the developmental mechanism, ensuring the
      predictability and stability of the acquired phenotype, comparable to that of
      native RGCs at biochemical, molecular, and functional levels. More importantly,
      the induced RGCs expressed axonal guidance molecules and demonstrated the
      potential to establish contacts with specific targets. Furthermore, when
      transplanted in the rat model of ocular hypertension, these cells incorporated
      into the host RGC layer and expressed RGC-specific markers. Transplantation of
      these cells in immune-deficient mice did not produce tumors. Together, our
      results posit retinal progenitors generated from non-nucleic acid-derived iPS
      cells as a safe and robust source of RGCs for replacing dead RGCs in glaucoma.

PMID- 25753400
TI  - Pathophysiology, diagnosis, and treatment of paroxysmal nocturnal hemoglobinuria:
      a review.
AB  - Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired disorder of the
      hematopoietic stem cell that makes blood cells more sensitive to the action of
      complement. Patients experience intravascular hemolysis, smooth muscle dystonia,
      renal failure, arterial and pulmonary hypertension, recurrent infectious diseases
      and an increased risk of notably dreadful thrombotic complications. The diagnosis
      is made by flow cytometry. Efforts have been recently performed to improve the
      sensitivity and the standardization of this technique. PNH is frequently
      associated with aplastic anemia or low-risk myelodysplasia and may be
      asymptomatic. Management of the classical form of PNH has been dramatically
      revolutionized by the development of eculizumab, which brings benefits in terms
      of hemolysis, quality of life, renal function, thrombotic risk, and life
      expectancy. Prophylaxis and treatment of arterial and venous thrombosis currently
      remain a challenge in PNH. 

PMID- 25753399
TI  - Women who are married or living as married have higher salivary estradiol and
      progesterone than unmarried women.
AB  - OBJECTIVES: Extensive research has demonstrated that marriage and parenting are
      associated with lower testosterone levels in men, however, very little is known
      about associations with hormone concentrations in women. Two studies have found
      lower testosterone in relation to pair-bonding and motherhood in women, with
      several others suggesting that estradiol levels are lower among parous women than
      nulliparous women. Here, we examine estradiol and progesterone concentrations in
      relation to marriage and motherhood in naturally cycling, reproductive age women.
      METHODS: In 185 Norwegian women, estradiol and progesterone concentrations were
      assayed from waking saliva samples collected daily over the course of a menstrual
      cycle. Cycles were aligned on day 0, the day of ovulation. Mean periovulatory
      estradiol (days -7 to +6) and luteal progesterone (day +2 to +10) indices were
      calculated. Marital status and motherhood (including age of youngest child) were
      reported in baseline questionnaires. Multivariable linear regression models were
      used to examine associations between ovarian hormones, marital status, and
      motherhood. RESULTS: Women who were married or living as married had higher
      estradiol than unmarried women (beta = 0.19; 95% CI: 0.02, 0.36) and higher
      luteal progesterone as well (beta = 0.19; 95% CI: -0.01, 0.39). There were no
      notable differences in hormone levels in relationship to motherhood status.
      CONCLUSIONS: Our results indicate that ovarian steroid hormones may be higher
      among women who are married or living as married, and suggest several possible
      explanations, however, additional research is needed to elucidate any causal
      relationships.

PMID- 25753402
TI  - The scope and practice of behaviour change communication to improve infant and
      young child feeding in low- and middle-income countries: results of a
      practitioner study in international development organizations.
AB  - We describe features of the landscape of behaviour change communication (BCC)
      practice devoted to infant and young child feeding (IYCF) in low- and middle
      income countries by practitioners in international development organizations. We
      used an iterative, snowball sampling procedure to identify participants, and the
      self-administered questionnaire contained pre-coded questions and open-ended
      questions, relying primarily on content analysis to derive generalizations.
      Highlights of findings include (i) IYCF-specific BCC is usually delivered within
      the context of other public health messages and programmes; (ii) technical
      assistance with programme development and implementation are primary activities,
      and evaluation-related work is also common; and (iii) formative research and
      evaluation is universal, but process evaluation is not. With respect to scaling
      up nutrition: (i) use of mass media and digital technology generally play only a
      minor role in BCC activities and are not currently an integral part of BCC
      programming strategies and (ii) only 58% of the participants report activities
      related to communication with policy makers. The individuals who comprise the
      community of BCC leaders in the area of IYCF are a diverse group from the
      perspective of academic backgrounds and nationalities. In addition to nutrition,
      public health, agriculture and adult learning are common disciplinary
      backgrounds. In our view, this diversity is a source of strength. It facilitates
      continuing growth and maturation in the field by assuring inputs of different
      perspectives, theoretical orientations and experiences. 

PMID- 25753401
TI  - Population pharmacokinetic analysis of raltegravir pediatric formulations in HIV
      infected children 4 weeks to 18 years of age.
AB  - P1066 is an open-label study of raltegravir in HIV positive youth, ages 4 weeks
      18 years. Here we summarize P1066 pharmacokinetic (PK) data and a population PK
      model for the pediatric chewable tablet and oral granules. Raltegravir PK
      parameters were calculated using noncompartmental analysis. A 2-compartment model
      was developed using data from P1066 and an adult study of the pediatric
      formulations. Interindividual variability was described by an exponential error
      model, and residual variability was captured by an additive/proportional error
      model. Twelve-hour concentrations (C12h ) were calculated from the model-derived
      elimination rate constant and 8-hour observed concentration. Simulated steady
      state concentrations were analyzed by noncompartmental analysis. Target area
      under the curve (AUC0-12h ) and C12h were achieved in each cohort. For the
      pediatric formulations, geometric mean AUC0-12h values were 18.0-22.6 MUM-hr
      across cohorts, and C12h values were 71-130 nM, with lower coefficients of
      variation versus the film-coated tablet. A 2-compartment model with first-order
      absorption adequately described raltegravir plasma PK in pediatric and adult
      patients. Weight was a covariate on clearance and central volume and was
      incorporated using allometric scaling. Raltegravir chewable tablets and oral
      granules exhibited PK parameters consistent with those from prior adult studies
      and older children in P1066, as well as lower variability than the film-coated
      tablet. 

PMID- 25753403
TI  - Neighborhood and housing disorder, parenting, and youth adjustment in low-income
      urban families.
AB  - Using two waves of data, this study examined relations among neighborhood and
      housing disorder, parents' psychological distress, parenting behaviors, and
      subsequent youth adjustment in a low-income, multiethnic sample of families with
      children aged 6-16. Results supported the hypothesized indirect relation between
      disorder and youth outcomes via parenting processes. Higher levels of
      neighborhood and housing disorder were associated with higher levels of parents'
      psychological distress, which was in turn related to more frequent use of harsh
      and inconsistent discipline strategies and lower parental warmth. More frequent
      use of harsh and inconsistent discipline was associated with higher levels of
      youth internalizing and externalizing behaviors 3 years later. Housing disorder
      contributed more strongly to parents' psychological distress than neighborhood
      disorder, whereas neighborhood disorder contributed more strongly to youth
      externalizing behaviors compared to housing disorder. Multiple-group analyses
      showed that the patterns of relations were similar for younger and older
      children, and for girls and boys.

PMID- 25753404
TI  - A patient-centered perspective of treating depressive symptoms in chronic heart
      failure: What do patients prefer?
AB  - OBJECTIVE: To date, very little is known about the specific needs of patients
      with chronic heart failure (CHF) who must cope with depression. We therefore
      questioned CHF patients reporting depressive symptoms about their concerns and
      preferences regarding various psychosocial treatment options. After three-month,
      we determined how many patients had actually participated in a treatment.
      METHODS: 85 patients with CHF fulfilling the criteria of a depressive disorder
      according to the PHQ-9 were investigated. Data were analyzed using descriptive
      and frequency, as well as logistic regression analyses. RESULTS: 64.7% of the
      sample reported that they could envision adhering to supportive talks at longer
      intervals, whereas only 34.1% would accept an antidepressant. After three months,
      24.7% of the patients had actually participated in a treatment. Generalized
      anxiety severity (GAD-7) was very closely associated with treatment preferences
      and treatment utilization: The higher the generalized anxiety severity, the more
      likely was the patients' disposition to begin an antidepressant and/or
      psychotherapy. CONCLUSIONS: The most favoured treatment option was a low
      threshold service with supportive talks. PRACTICE IMPLICATIONS: Future studies
      investigating the improvement of patient-centred care in CHF patients should
      include measurements of generalized anxiety.

PMID- 25753405
TI  - Werner R. Loewenstein : Feb. 14, 1926-Nov. 17, 2014.

PMID- 25753406
TI  - Maskless milling of diamond by a focused oxygen ion beam.
AB  - Recent advances in focused ion beam technology have enabled high-resolution,
      maskless nanofabrication using light ions. Studies with light ions to date have,
      however, focused on milling of materials where sub-surface ion beam damage does
      not inhibit device performance. Here we report on maskless milling of single
      crystal diamond using a focused beam of oxygen ions. Material quality is assessed
      by Raman and luminescence analysis, and reveals that the damage layer generated
      by oxygen ions can be removed by non-intrusive post-processing methods such as
      localised electron beam induced chemical etching. 

PMID- 25753407
TI  - Paediatric non-alcoholic fatty liver disease: an overview.
AB  - Non-alcoholic fatty liver disease (NAFLD) is a progressive disease that
      encompasses a spectrum of liver diseases, ranging from simple steatosis to non
      alcoholic steatohepatitis (NASH). Data related to survival in children are
      scarce, but these data firmly associate NAFLD with higher risks of hepatic and
      non-hepatic morbidities and mortalities compared with the general population.
      More recently, the association between NAFLD and cardiovascular disease among
      children has increasingly been recognized. Given that obesity is a major risk
      factor for the disease, paediatric NAFLD is becoming a global issue, paralleling
      the dramatic rise in obesity worldwide. NASH, which is more common in obese
      children, has the potential to advance to liver fibrosis and failure. It is
      unclear why certain patients undergo such transformation but this susceptibility
      is likely related to an interaction between a genetically susceptible host and
      the surrounding environment. Currently, treatment is largely conservative and
      includes lifestyle modification, attainable through healthy weight reduction via
      diet and exercise. In this review, current knowledge about NAFLD in children is
      summarized. This review aims to increase the awareness of the medical community
      about a hidden public health issue and to identify current gaps in the literature
      while providing directions for future research. 

PMID- 25753408
TI  - Maternal vitamin D deficiency alters fetal brain development in the BALB/c mouse.
AB  - Prenatal exposure to vitamin D is thought to be critical for optimal fetal
      neurodevelopment, yet vitamin D deficiency is apparent in a growing proportion of
      pregnant women. The aim of this study was to determine whether a mouse model of
      vitamin D-deficiency alters fetal neurodevelopment. Female BALB/c mice were
      placed on either a vitamin D control (2,195 IU/kg) or deficient (0 IU/kg) diet
      for 5 weeks prior to and during pregnancy. Fetal brains were collected at
      embryonic day (E) 14.5 or E17.5 for morphological and gene expression analysis.
      Vitamin D deficiency during pregnancy reduced fetal crown-rump length and head
      size. Moreover, lateral ventricle volume was reduced in vitamin D-deficient
      foetuses. Expression of neurotrophin genes brain-derived neurotrophic factor
      (Bdnf) and transforming growth factor-beta1 (Tgf-beta1) was altered, with Bdnf
      reduced at E14.5 and increased at E17.5 following vitamin D deficiency. Brain
      expression of forkhead box protein P2 (Foxp2), a gene known to be important in
      human speech and language, was also altered. Importantly, Foxp2 immunoreactive
      cells in the developing cortex were reduced in vitamin D-deficient female
      foetuses. At E17.5, brain tyrosine hydroxylase (TH) gene expression was reduced
      in females, as was TH protein localization (to identify dopamine neurons) in the
      substantia nigra of vitamin D-deficient female foetuses. Overall, we show that
      prenatal vitamin D-deficiency leads to alterations in fetal mouse brain
      morphology and genes related to neuronal survival, speech and language
      development, and dopamine synthesis. Vitamin D appears to play an important role
      in mouse neurodevelopment.

PMID- 25753409
TI  - Prefrontal and Auditory Input to Intercalated Neurons of the Amygdala.
AB  - The basolateral amygdala (BLA) and prefrontal cortex (PFC) are partners in fear
      learning and extinction. Intercalated (ITC) cells are inhibitory neurons that
      surround the BLA. Lateral ITC (lITC) neurons provide feed-forward inhibition to
      BLA principal neurons, whereas medial ITC (mITC) neurons form an inhibitory
      interface between the BLA and central amygdala (CeA). Notably, infralimbic
      prefrontal (IL) input to mITC neurons is thought to play a key role in fear
      extinction. Here, using targeted optogenetic stimulation, we show that lITC
      neurons receive auditory input from cortical and thalamic regions. IL inputs
      innervate principal neurons in the BLA but not mITC neurons. These results
      suggest that (1) these neurons may play a more central role in fear learning as
      both lITCs and mITCs receive auditory input and that (2) mITC neurons cannot be
      driven directly by the IL, and their role in fear extinction is likely mediated
      via the BLA.

PMID- 25753410
TI  - Regulation of Autocrine Signaling in Subsets of Sympathetic Neurons Has Regional
      Effects on Tissue Innervation.
AB  - The regulation of innervation by target-derived factors like nerve growth factor
      (NGF) is the cornerstone of neurotrophic theory. Whereas autocrine signaling in
      neurons affecting survival and axon growth has been described, it is difficult to
      reconcile autocrine signaling with the idea that targets control their
      innervation. Here, we report that an autocrine signaling loop in developing mouse
      sympathetic neurons involving CD40L (TNFSF5) and CD40 (TNFRSF5) selectively
      enhances NGF-promoted axon growth and branching, but not survival, via CD40L
      reverse signaling. Because NGF negatively regulates CD40L and CD40 expression,
      this signaling loop operates only in neurons exposed to low levels of NGF.
      Consequently, the sympathetic innervation density of tissues expressing low NGF
      is significantly reduced in CD40-deficient mice, whereas the innervation density
      of tissues expressing high levels of NGF is unaffected. Our findings reveal how
      differential regulation of autocrine signaling in neurons has region-specific
      effects on axon growth and tissue innervation.

PMID- 25753411
TI  - A Subtype of Inhibitory Interneuron with Intrinsic Persistent Activity in Human
      and Monkey Neocortex.
AB  - A critical step in understanding the neural basis of human cognitive functions is
      to identify neuronal types in the neocortex. In this study, we performed whole
      cell recording from human cortical slices and found a distinct subpopulation of
      neurons with intrinsic persistent activity that could be triggered by single
      action potentials (APs) but terminated by bursts of APs. This persistent activity
      was associated with a depolarizing plateau potential induced by the activation of
      a persistent Na+ current. Single-cell RT-PCR revealed that these neurons were
      inhibitory interneurons. This type of neuron was found in different cortical
      regions, including temporal, frontal, occipital, and parietal cortices in human
      and also in frontal and temporal lobes of nonhuman primate but not in rat
      cortical tissues, suggesting that it could be unique to primates. The
      characteristic persistent activity in these inhibitory interneurons may
      contribute to the regulation of pyramidal cell activity and participate in
      cortical processing.

PMID- 25753412
TI  - Coordination between Translation and Degradation Regulates Inducibility of mGluR
      LTD.
AB  - Dendritic protein homeostasis is crucial for most forms of long-term synaptic
      plasticity, and its dysregulation is linked to a wide range of brain disorders.
      Current models of metabotropic glutamate receptor mediated long-term depression
      (mGluR-LTD) suggest that rapid, local synthesis of key proteins is necessary for
      the induction and expression of LTD. Here, we find that mGluR-LTD can be induced
      in the absence of translation if the proteasome is concurrently inhibited. We
      report that enhanced proteasomal degradation during the expression of mGluR-LTD
      depletes dendritic proteins and inhibits subsequent inductions of LTD. Moreover,
      proteasome inhibition can rescue mGluR-LTD in mice null for the RNA binding
      protein Sam68, which we show here lack mGluR-dependent translation and LTD. Our
      study provides mechanistic insights for how changes in dendritic protein
      abundance regulate mGluR-LTD induction. We propose that Sam68-mediated
      translation helps to counterbalance degradation, ensuring that protein levels
      briefly remain above a permissive threshold during LTD induction.

PMID- 25753413
TI  - Structural and Mechanistic Analysis of the Slx1-Slx4 Endonuclease.
AB  - The SLX1-SLX4 endonuclease required for homologous recombination and DNA repair
      in eukaryotic cells cleaves a variety of branched DNA structures. The nuclease
      subunit SLX1 is activated by association with a scaffolding protein SLX4. At the
      present time, little is known about the structure of SLX1-SLX4 or its mechanism
      of action. Here, we report the structural insights into SLX1-SLX4 by detailing
      the crystal structure of Candida glabrata (Cg) Slx1 alone and in combination with
      the C-terminal region of Slx4. The structure of Slx1 reveals a compact
      arrangement of the GIY-YIG nuclease and RING domains, which is reinforced by a
      long alpha helix. Slx1 forms a stable homodimer that blocks its active site. Slx1
      Slx4 interaction is mutually exclusive with Slx1 homodimerization, suggesting a
      mechanism for Slx1 activation by Slx4.

PMID- 25753414
TI  - N-Cadherin Induction by ECM Stiffness and FAK Overrides the Spreading Requirement
      for Proliferation of Vascular Smooth Muscle Cells.
AB  - In contrast to the accepted pro-proliferative effect of cell-matrix adhesion, the
      proliferative effect of cadherin-mediated cell-cell adhesion remains unresolved.
      Here, we studied the effect of N-cadherin on cell proliferation in the
      vasculature. We show that N-cadherin is induced in smooth muscle cells (SMCs) in
      response to vascular injury, an in vivo model of tissue stiffening and
      proliferation. Complementary experiments performed with deformable substrata
      demonstrated that stiffness-mediated activation of a focal adhesion kinase (FAK)
      p130Cas-Rac signaling pathway induces N-cadherin. Additionally, by culturing
      paired and unpaired SMCs on microfabricated adhesive islands of different areas,
      we found that N-cadherin relaxes the spreading requirement for SMC proliferation.
      In vivo SMC deletion of N-cadherin strongly reduced injury-induced cycling.
      Finally, SMC-specific deletion of FAK inhibited proliferation after vascular
      injury, and this was accompanied by reduced induction of N-cadherin. Thus, a
      stiffness- and FAK-dependent induction of N-cadherin connects cell-matrix to cell
      cell adhesion and regulates the degree of cell spreading needed for cycling.

PMID- 25753415
TI  - IgE/FcepsilonRI-Mediated Antigen Cross-Presentation by Dendritic Cells Enhances
      Anti-Tumor Immune Responses.
AB  - Epidemiologic studies discovered an inverse association between immunoglobulin E
      (IgE)-mediated allergies and cancer, implying tumor-protective properties of IgE.
      However, the underlying immunologic mechanisms remain poorly understood. Antigen
      cross-presentation by dendritic cells (DCs) is of key importance for anti-tumor
      immunity because it induces the generation of cytotoxic CD8+ T lymphocytes (CTLs)
      with specificity for tumor antigens. We demonstrate that DCs use IgE and
      FcepsilonRI, the high-affinity IgE receptor, for cross-presentation and priming
      of CTLs in response to free soluble antigen at low doses. Importantly,
      IgE/FcepsilonRI-mediated cross-presentation is a distinct receptor-mediated
      pathway because it does not require MyD88 signals or IL-12 induction in DCs.
      Using passive immunization with tumor antigen-specific IgE and DC-based
      vaccination experiments, we demonstrate that IgE-mediated cross-presentation
      significantly improves anti-tumor immunity and induces memory responses in vivo.
      Our findings suggest a cellular mechanism for the tumor-protective features of
      IgE and expand the known physiological functions of this immunoglobulin.

PMID- 25753416
TI  - KDEL Receptors Assist Dengue Virus Exit from the Endoplasmic Reticulum.
AB  - Membrane receptors at the surface of target cells are key host factors for virion
      entry; however, it is unknown whether trafficking and secretion of progeny virus
      requires host intracellular receptors. In this study, we demonstrate that dengue
      virus (DENV) interacts with KDEL receptors (KDELR), which cycle between the ER
      and Golgi apparatus, for vesicular transport from ER to Golgi. Depletion of KDELR
      by siRNA reduced egress of both DENV progeny and recombinant subviral particles
      (RSPs). Coimmunoprecipitation of KDELR with dengue structural protein prM
      required three positively charged residues at the N terminus, whose mutation
      disrupted protein interaction and inhibited RSP transport from the ER to the
      Golgi. Finally, siRNA depletion of class II Arfs, which results in KDELR
      accumulation in the Golgi, phenocopied results obtained with mutagenized prME and
      KDELR knockdown. Our results have uncovered a function for KDELR as an internal
      receptor involved in DENV trafficking.

PMID- 25753417
TI  - Heterogeneities in Nanog Expression Drive Stable Commitment to Pluripotency in
      the Mouse Blastocyst.
AB  - The pluripotent epiblast (EPI) is the founder tissue of almost all somatic cells.
      EPI and primitive endoderm (PrE) progenitors arise from the inner cell mass (ICM)
      of the blastocyst-stage embryo. The EPI lineage is distinctly identified by its
      expression of pluripotency-associated factors. Many of these factors have been
      reported to exhibit dynamic fluctuations of expression in embryonic stem cell
      cultures. Whether these fluctuations correlating with ICM fate choice occur in
      vivo remains an open question. Using single-cell resolution quantitative imaging
      of a Nanog transcriptional reporter, we noted an irreversible commitment to
      EPI/PrE lineages in vivo. A period of apoptosis occurred concomitantly with ICM
      cell-fate choice, followed by a burst of EPI-specific cell proliferation.
      Transitions were occasionally observed from PrE-to-EPI, but not vice versa,
      suggesting that they might be regulated and not stochastic. We propose that the
      rapid timescale of early mammalian embryonic development prevents fluctuations in
      cell fate.

PMID- 25753419
TI  - Directional R-Loop Formation by the CRISPR-Cas Surveillance Complex Cascade
      Provides Efficient Off-Target Site Rejection.
AB  - CRISPR-Cas systems provide bacteria and archaea with adaptive immunity against
      foreign nucleic acids. In type I CRISPR-Cas systems, invading DNA is detected by
      a large ribonucleoprotein surveillance complex called Cascade. The crRNA
      component of Cascade is used to recognize target sites in foreign DNA
      (protospacers) by formation of an R-loop driven by base-pairing complementarity.
      Using single-molecule supercoiling experiments with near base-pair resolution, we
      probe here the mechanism of R-loop formation and detect short-lived R-loop
      intermediates on off-target sites bearing single mismatches. We show that R-loops
      propagate directionally starting from the protospacer-adjacent motif (PAM). Upon
      reaching a mismatch, R-loop propagation stalls and collapses in a length
      dependent manner. This unambiguously demonstrates that directional zipping of the
      R-loop accomplishes efficient target recognition by rapidly rejecting binding to
      off-target sites with PAM-proximal mutations. R-loops that reach the protospacer
      end become locked to license DNA degradation by the auxiliary Cas3
      nuclease/helicase without further target verification.

PMID- 25753418
TI  - Repression of the Central Splicing Regulator RBFox2 Is Functionally Linked to
      Pressure Overload-Induced Heart Failure.
AB  - Heart failure is characterized by the transition from an initial compensatory
      response to decompensation, which can be partially mimicked by transverse aortic
      constriction (TAC) in rodent models. Numerous signaling molecules have been shown
      to be part of the compensatory program, but relatively little is known about the
      transition to decompensation that leads to heart failure. Here, we show that TAC
      potently decreases the RBFox2 protein in the mouse heart, and cardiac ablation of
      this critical splicing regulator generates many phenotypes resembling those
      associated with decompensation in the failing heart. Global analysis reveals that
      RBFox2 regulates splicing of many genes implicated in heart function and disease.
      A subset of these genes undergoes developmental regulation during postnatal heart
      remodeling, which is reversed in TAC-treated and RBFox2 knockout mice. These
      findings suggest that RBFox2 may be a critical stress sensor during pressure
      overload-induced heart failure.

PMID- 25753420
TI  - Ascl1 Coordinately Regulates Gene Expression and the Chromatin Landscape during
      Neurogenesis.
AB  - The proneural transcription factor Ascl1 coordinates gene expression in both
      proliferating and differentiating progenitors along the neuronal lineage. Here,
      we used a cellular model of neurogenesis to investigate how Ascl1 interacts with
      the chromatin landscape to regulate gene expression when promoting neuronal
      differentiation. We find that Ascl1 binding occurs mostly at distal enhancers and
      is associated with activation of gene transcription. Surprisingly, the
      accessibility of Ascl1 to its binding sites in neural stem/progenitor cells
      remains largely unchanged throughout their differentiation, as Ascl1 targets
      regions of both readily accessible and closed chromatin in proliferating cells.
      Moreover, binding of Ascl1 often precedes an increase in chromatin accessibility
      and the appearance of new regions of open chromatin, associated with de novo gene
      expression during differentiation. Our results reveal a function of Ascl1 in
      promoting chromatin accessibility during neurogenesis, linking the chromatin
      landscape at Ascl1 target regions with the temporal progression of its
      transcriptional program.

PMID- 25753421
TI  - Accumulation of Basic Amino Acids at Mitochondria Dictates the Cytotoxicity of
      Aberrant Ubiquitin.
AB  - Neuronal accumulation of UBB+1, a frameshift variant of ubiquitin B, is a
      hallmark of Alzheimer's disease (AD). How UBB+1 contributes to neuronal
      dysfunction remains elusive. Here, we show that in brain regions of AD patients
      with neurofibrillary tangles UBB+1 co-exists with VMS1, the mitochondrion
      specific component of the ubiquitin-proteasome system (UPS). Expression of UBB+1
      in yeast disturbs the UPS, leading to mitochondrial stress and apoptosis.
      Inhibiting UPS activity exacerbates while stimulating UPS by the transcription
      activator Rpn4 reduces UBB+1-triggered cytotoxicity. High levels of the Rpn4
      target protein Cdc48 and its cofactor Vms1 are sufficient to relieve programmed
      cell death. We identified the UBB+1-induced enhancement of the basic amino acids
      arginine, ornithine, and lysine at mitochondria as a decisive toxic event, which
      can be reversed by Cdc48/Vms1-mediated proteolysis. The fact that AD-induced
      cellular dysfunctions can be avoided by UPS activity at mitochondria has
      potentially far-reaching pathophysiological implications.

PMID- 25753422
TI  - PGC-1/Spargel Counteracts High-Fat-Diet-Induced Obesity and Cardiac Lipotoxicity
      Downstream of TOR and Brummer ATGL Lipase.
AB  - Obesity and metabolic syndrome are associated with an increased risk for
      lipotoxic cardiomyopathy, which is strongly correlated with excessive
      accumulation of lipids in the heart. Obesity- and type-2-diabetes-related
      disorders have been linked to altered expression of the transcriptional cofactor
      PGC-1alpha, which regulates the expression of genes involved in energy
      metabolism. Using Drosophila, we identify PGC-1/spargel (PGC-1/srl) as a key
      antagonist of high-fat diet (HFD)-induced lipotoxic cardiomyopathy. We find that
      HFD-induced lipid accumulation and cardiac dysfunction are mimicked by reduced
      PGC-1/srl function and reversed by PGC-1/srl overexpression. Moreover, HFD
      feeding lowers PGC-1/srl expression by elevating TOR signaling and inhibiting
      expression of the Drosophila adipocyte triglyceride lipase (ATGL) (Brummer), both
      of which function as upstream modulators of PGC-1/srl. The lipogenic
      transcription factor SREBP also contributes to HFD-induced cardiac lipotoxicity,
      likely in parallel with PGC-1/srl. These results suggest a regulatory network of
      key metabolic genes that modulates lipotoxic heart dysfunction.

PMID- 25753423
TI  - Loss-of-Function Mutation in APC2 Causes Sotos Syndrome Features.
AB  - Sotos syndrome, characterized by intellectual disability and characteristic
      facial features, is caused by haploinsufficiency in the NSD1 gene. We conducted
      an etiological study on two siblings with Sotos features without mutations in
      NSD1 and detected a homozygous frameshift mutation in the APC2 gene by whole
      exome sequencing, which resulted in the loss of function of cytoskeletal
      regulation in neurons. Apc2-deficient (Apc2-/-) mice exhibited impaired learning
      and memory abilities along with an abnormal head shape. Endogenous Apc2
      expression was downregulated by the knockdown of Nsd1, indicating that APC2 is a
      downstream effector of NSD1 in neurons. Nsd1 knockdown in embryonic mouse brains
      impaired the migration and laminar positioning of cortical neurons, as observed
      in Apc2-/- mice, and this defect was rescued by the forced expression of Apc2.
      Thus, APC2 is a crucial target of NSD1, which provides an explanation for the
      intellectual disability associated with Sotos syndrome.

PMID- 25753424
TI  - ErbB2 Pathway Activation upon Smad4 Loss Promotes Lung Tumor Growth and
      Metastasis.
AB  - Lung cancer remains the leading cause of cancer death. Genome sequencing of lung
      tumors from patients with squamous cell carcinoma has identified SMAD4 to be
      frequently mutated. Here, we use a mouse model to determine the molecular
      mechanisms by which Smad4 loss leads to lung cancer progression. Mice with
      ablation of Pten and Smad4 in airway epithelium develop metastatic adenosquamous
      tumors. Comparative transcriptomic and in vivo cistromic analyses determine that
      loss of PTEN and SMAD4 results in ELF3 and ErbB2 pathway activation due to
      decreased expression of ERRFI1, a negative regulator of ERBB2 in mouse and human
      cells. The combinatorial inhibition of ErbB2 and Akt signaling attenuate tumor
      progression and cell invasion, respectively. Expression profile analysis of human
      lung tumors substantiated the importance of the ErbB2/Akt/ELF3 signaling pathway
      as both a prognostic biomarker and a therapeutic drug target for treating lung
      cancer.

PMID- 25753425
TI  - M-CSF from Cancer Cells Induces Fatty Acid Synthase and PPARbeta/delta Activation
      in Tumor Myeloid Cells, Leading to Tumor Progression.
AB  - We investigate crosstalk between cancer cells and stromal myeloid cells. We find
      that Lewis lung carcinoma cells significantly induce PPARbeta/delta activity in
      myeloid cells in vitro and in vivo. Myeloid cell-specific knockout of
      PPARbeta/delta results in impaired growth of implanted tumors, and this is
      restored by adoptive transfer of wild-type myeloid cells. We find that IL-10 is a
      downstream effector of PPARbeta/delta and facilitates tumor cell invasion and
      angiogenesis. This observation is supported by the finding that the CD11blowIL
      10+ pro-tumoral myeloid cell is scarcely detected in tumors from myeloid-cell
      specific PPARbeta/delta knockout mice, where vessel densities are also decreased.
      Fatty acid synthase (FASN) is shown to be an upstream regulator of PPARbeta/delta
      in myeloid cells and is induced by M-CSF secreted from tumor cells. Our study
      gives insight into how cancer cells influence myeloid stromal cells to get a pro
      tumoral phenotype.

PMID- 25753426
TI  - Microglia-Secreted Galectin-3 Acts as a Toll-like Receptor 4 Ligand and
      Contributes to Microglial Activation.
AB  - Inflammatory response induced by microglia plays a critical role in the demise of
      neuronal populations in neuroinflammatory diseases. Although the role of toll
      like receptor 4 (TLR4) in microglia's inflammatory response is fully
      acknowledged, little is known about endogenous ligands that trigger TLR4
      activation. Here, we report that galectin-3 (Gal3) released by microglia acts as
      an endogenous paracrine TLR4 ligand. Gal3-TLR4 interaction was further confirmed
      in a murine neuroinflammatory model (intranigral lipopolysaccharide [LPS]
      injection) and in human stroke subjects. Depletion of Gal3 exerted
      neuroprotective and anti-inflammatory effects following global brain ischemia and
      in the neuroinflammatory LPS model. These results suggest that Gal3-dependent
      TLR4 activation could contribute to sustained microglia activation, prolonging
      the inflammatory response in the brain.

PMID- 25753427
TI  - Diversity and evolution of potato mop-top virus.
AB  - Nearly complete sequences of RNA-CP and 3'-proximal RNA-TGB were determined for
      43 samples of potato mop-top virus (PMTV) originating from potato tubers and
      field soil from Sweden, Denmark and the USA. The results showed limited diversity
      and no strict geographical grouping, suggesting only a few original introductions
      of PMTV from the Andes. Two distinguishable types of RNA-CP and RNA-TGB were
      found in the samples, but no specific combination of them correlated with spraing
      symptoms in tubers. Lack of positive selection in the coding sequences indicates
      that there is no specific molecular adaptation of PMTV to new vectors or hosts. 

PMID- 25753428
TI  - Low-temperature bacterial viruses VR - a small but diverse group of E. coli
      phages.
AB  - The complete genome sequences of four low-temperature Escherichia coli-specific
      tevenviruses, vb_EcoM-VR5, vb_EcoM-VR20, vb_EcoM-VR25 and vb_EcoM-VR26, were
      determined. Genomic comparisons including recently described genomes of vb_EcoM
      VR7 and JS98 as well as phage T4 allowed the identification of two genetic groups
      that were consistent with defined host-range phenotypes. Group A included the
      broad-host-range phages vb_EcoM-VR5 and JS98, while group B included vb_EcoM-VR7,
      vb_EcoM-VR20, vb_EcoM-VR25 and vb_EcoM-VR26, which all had somewhat limited host
      ranges. All four sequenced phages had genomes that were similar in length (~170
      kb) and GC content (~40 %), and, with the exception of vb_EcoM-VR5, at the
      nucleotide level, they were much more closely related to each other than either
      was to any other tevenvirus currently characterized. Nevertheless, the overall
      genome organization of vb_EcoM-VR5, vb_EcoM-VR20, vb_EcoM-VR25 and vb_EcoM-VR26
      was comparable to that seen in tevenviruses.

PMID- 25753429
TI  - Efficacy, Safety, and Predictors of Intradiscal Methylene Blue Injection for
      Discogenic Low Back Pain: Results of a Multicenter Prospective Clinical Series.
AB  - STUDY DESIGN: Prospective clinical study of intradiscal methylene blue injection
      for the treatment of lumbar discogenic pain. OBJECTIVE: The objective of this
      study was to collect information about efficacy, safety, and acceptability of the
      intervention, gain and burden of outcome measures, and sample size assumptions
      for a potential following randomized controlled trial (RCT). If the pilot study
      demonstrates that this treatment is potentially effective and safe, and the
      methods and procedures used in this study are feasible, a RCT follows. SUMMARY OF
      BACKGROUND DATA: Low back pain (LBP) is a highly common problem with a lifetime
      prevalence of more than 70%. A substantial part of chronic LBP is attributable to
      degenerative changes in the intervertebral disc. A recently published RCT
      assessing the treatment intradiscal injection of methylene blue for chronic
      discogenic LBP, showed exceptionally good results. METHODS: Patients were
      selected on clinical criteria, magnetic resonance imaging, and a positive
      provocative discogram. The primary outcome measure was mean pain reduction at 6
      months. RESULTS: Fifteen consecutive patients with chronic lumbar discogenic pain
      enrolled in a multicenter prospective case series in two interventional pain
      treatment centers in the Netherlands. Six months after the intervention, 40% of
      the patients claimed at least 30% pain relief. In patients who responded,
      physical function improved and medication use diminished. We observed no
      procedural complications or adverse events. Predictors for success were Pfirrmann
      grading of 2 or less and higher quality of life mental component scores.
      CONCLUSIONS: Our findings of 40% positive respondents, and no complications, give
      reason to set up a randomized, double-blind, placebo-controlled, trial.

PMID- 25753430
TI  - Carbazole dendrimers as solution-processable thermally activated delayed
      fluorescence materials.
AB  - Recently, thermally activated delayed fluorescence (TADF) materials have received
      increasing attention as effective emitters for organic light-emitting diodes
      (OLEDs). However, most of them are usually employed as dopants in a host
      material. In this report, carbazole dendrimers with a triphenyl-s-triazine core
      are reported, which are the first solution-processable, non-doped, high-molecular
      weight TADF materials. The dendrimers were obtained by a new and facile synthetic
      route using the tert-butyldimethylsilyl moiety as a protecting group. All
      dendrimers showed TADF in toluene. Measurements of the temperature-dependent
      luminescence lifetime revealed that spin-coated neat films also showed TADF with
      moderate quantum yields. OLED devices incorporating these dendrimers as spin
      coated emitting layers gave external quantum efficiencies of up to a 3.4 %, which
      suggests that this device is harvesting triplet excitons. This result indicates
      that carbazole dendrimers with attached acceptors are potential TADF materials
      owing to their polarized electronic structure (with HOMO-LUMO separation).

PMID- 25753431
TI  - CMR May Predict VT in ICM. How About in Better Hearts, Does It Really Work?

PMID- 25753433
TI  - Reply to a. Molfino et Al.

PMID- 25753432
TI  - Stem-cell transplantation in children with acute lymphoblastic leukemia: A
      prospective international multicenter trial comparing sibling donors with matched
      unrelated donors-The ALL-SCT-BFM-2003 trial.
AB  - PURPOSE: Although hematopoietic stem-cell transplantation is widely performed in
      children with high-risk acute lymphoblastic leukemia (ALL), the influence of
      donor types is poorly understood. Thus, transplantation outcomes were compared in
      the prospective multinational Berlin-Frankfurt-Muenster (BFM) study group trial:
      ALL-SCT-BFM 2003 (Allogeneic Stem Cell Transplantation in Children and
      Adolescents with Acute Lymphoblastic Leukemia). PATIENTS AND METHODS: After
      conditioning with total-body irradiation and etoposide, 411 children with high
      risk ALL received highly standardized stem-cell transplantations during the first
      or later remissions. Depending on donor availability, grafts originated from HLA
      genoidentical siblings or from HLA-matched unrelated donors who were identified
      and matched by high-resolution allelic typing and were compatible in at least 9
      of 10 HLA loci. RESULTS: Four-year event-free survival (+/- standard deviation
      [SD]) did not differ between patients with transplantations from unrelated or
      sibling donors (0.67 +/- 0.03 v 0.71 +/- 0.05; P = .405), with cumulative
      incidences of nonrelapse mortality (+/- SD) of 0.10 +/- 0.02 and 0.03 +/- 0.02 (P
      = .017) and relapse rates (+/- SD) of 0.22 +/- 0.02 and 0.24 +/- 0.04 (P = .732),
      respectively. Among recipients of transplantations from unrelated donors, no
      significant differences in event-free survival, overall survival, or nonrelapse
      mortality were observed between 9/10 and 10/10 matched grafts or between
      peripheral blood stem cells and bone marrow. The absence of chronic graft-versus
      host disease had no effect on event-free survival. Engraftment was faster after
      bone marrow transplantation from siblings and was associated with fewer severe
      infections and pulmonary complications. CONCLUSION: Outcome among high-risk
      pediatric patients with ALL after hematopoietic stem-cell transplantation was not
      affected by donor type. Standardized myeloablative conditioning produced a low
      incidence of treatment-related mortality and effective control of leukemia.

PMID- 25753434
TI  - IGF2BP1 harbors prognostic significance by gene gain and diverse expression in
      neuroblastoma.
AB  - PURPOSE: Chromosomal 17q21-ter gain in neuroblastoma is both a common and
      prognostically significant event. The insulin-like growth factor-2 mRNA-binding
      protein 1 (IGF2BP1) gene is located near the proximal edge of this region. Here,
      its prognostic value is evaluated in neuroblastoma. METHODS: The mRNA expression
      of IGF2BP family members was first evaluated by microarray data sets. In
      addition, in a separate cohort of 69 tumors, IGF2BP1 gene copy number, mRNA, and
      protein abundance were determined and compared with clinical parameters. RESULTS:
      In two independent microarray data sets, 77% to 100% of tumors had substantial
      IGF2BP1 mRNA levels measured. High IGF2BP1 transcript abundance was significantly
      associated with stage 4 tumors (P < .001) and decreased patient survival (P <
      .001). IGF2BP1 was also associated with MYCN gene amplification and MYCN mRNA
      abundance. In the 69 neuroblastoma samples, IGF2BP1 DNA copy number (increased in
      84% of tumors), mRNA, and protein abundance were significantly higher in stage 4
      compared with stage 1 tumors. Importantly, IGF2BP1 protein levels were associated
      with lower overall patient survival (P = .012) and positively correlated with
      MYCN mRNA, even when excluding MYCN-amplified tumors. Moreover, IGF2BP1 clearly
      affected MYCN expression and neuroblastoma cell survival in vitro. CONCLUSION: In
      neuroblastoma, IGF2BP1 was expressed in the majority of neuroblastoma specimens
      analyzed and was associated with lower overall patient survival and MYCN
      abundance. These data demonstrate that IGF2BP1 is a potential oncogene and an
      independent negative prognostic factor in neuroblastoma.

PMID- 25753435
TI  - Heritage-specific mechanisms for cancer adverse reactions: one gene does not
      explain the world.

PMID- 25753436
TI  - Profound answers to simple questions.

PMID- 25753437
TI  - Tumor-infiltrating lymphocytes in breast cancer: ready for prime time?

PMID- 25753438
TI  - Tumor-infiltrating lymphocytes in triple-negative breast cancer: a biomarker for
      use beyond prognosis?

PMID- 25753439
TI  - Anorexia assessment in patients with cancer: a crucial issue to improve the
      outcome.

PMID- 25753440
TI  - National guidelines and level of evidence: comments on some of the new
      recommendations in the American Society of Clinical Oncology and the College of
      American Pathologists human epidermal growth factor receptor 2 guidelines for
      breast cancer.

PMID- 25753441
TI  - Reply to E.A. Rakha et al.

PMID- 25753442
TI  - Reply to A. Ocana et al and P.G. Tsoutsou et al.

PMID- 25753443
TI  - Journal Honors Steven M. Corsello, MD, as recipient of the 2014 JCO Young
      Investigator Award.

PMID- 25753444
TI  - Cardiovascular disease associated with androgen-deprivation therapy: time to give
      it due respect.

PMID- 25753445
TI  - FAmily-Led RehabiliTaTion aftEr Stroke in INDia: the ATTEND pilot study.
AB  - BACKGROUND: The aim of this pilot study was to determine the feasibility of a
      multicenter, randomized, controlled trial in India of a family-led, trained
      caregiver-delivered, home-based rehabilitation intervention vs. routine care.
      METHODS: A prospective, randomized (within seven-days of hospital admission),
      blinded outcome assessor, controlled trial of structured home-based
      rehabilitation delivered by trained and protocol-guided family caregivers
      (intervention) vs. routine care alone (control) was conducted in patients with
      residual disability. Key feasibility measures were recruitment, acceptance and
      adherence to assessment procedures, and follow-up of participants over six
      months. CTRI/2014/10/005133. RESULTS: A total of 104 patients from the stroke
      unit at Christian Medical College, Ludhiana were recruited over nine-months.
      Recruitment was feasible and accepted by patients and their carers. Important
      observations were made regarding potential unblinding of the participants,
      contamination of therapy between the randomized groups, organization of home
      visits, and resources required for a multicenter study. CONCLUSION: The pilot
      study established the feasibility of conducting a large-scale study of family
      led, trained caregiver-delivered, home-based stroke rehabilitation in a low
      resource setting. The main phase of the trial 'ATTEND' is currently underway in
      over 10 centers in India.

PMID- 25753446
TI  - Coloured sweat in two brothers: First report of familial chromhidrosis.
AB  - The uncommon diagnosis of chromhidrosis is most frequently made in young adults.
      This sweat gland disease, although benign, may impact significantly on the
      patient's quality of life. We describe the first report of familial chromhidrosis
      of pseudo-eccrine type (pseudochromhidrosis) occurring in two brothers aged 9 and
      12 years. The classification and causality of chromhidrosis is described and
      approaches to assessment and management are outlined. 

PMID- 25753447
TI  - Effect of topical application of chlorhexidine and metronidazole on the tissue
      repair of palatal wounds of rats: a clinical and histomorphometric study.
AB  - OBJECTIVE: This study investigated the effect of topical application of 2%
      chlorhexidine (GCl) and metronidazole (Gme) pastes for the repair of palatal
      wounds in rats. STUDY DESIGN: A 4-mm diameter wound was created on the palates of
      27 rats separated randomly into 3 groups of 9 animals each, according to the
      treatment received: GNa (Control: natrosol), GCl, and GMe. The animals were
      euthanized after 3, 6, and 10 days, and wound closure was clinically and
      histomorphometrically assessed. RESULTS: Clinical evaluation showed a
      statistically significant difference in tissue repair with GCl and GMe compared
      with GNa. In histomorphometric analysis, the highest values in the areas of the
      epithelium and keratin were observed for GCl and GMe; however, compared with Gna,
      no statistically significant differences were observed. CONCLUSIONS: GCl and GMe
      pastes showed promising results with regard to tissue repair from a clinical
      point of view. Histologically, premature closure of wounds was noted in most
      specimens on day 6. Although no statistically significant differences were
      observed among the experimental groups with regard to histometry of the
      epithelium and keratin, the highest means were observed for GCl.

PMID- 25753448
TI  - Systemic diseases and the risk of developing salivary stones: a case control
      study.
AB  - OBJECTIVE: To investigate the possible relationship between the presence of
      salivary stones and systemic diseases, medication, smoking, and alcohol
      consumption. STUDY DESIGN: A retrospective, case control study. Medical records
      of patients with salivary stones and those of control patients without salivary
      stones were retrospectively reviewed. Data regarding the affected salivary gland,
      the presence of systemic disease, and the use of medication, tobacco, and alcohol
      were recorded. Statistical analysis was performed using the Fisher Exact tests.
      RESULTS: Medical records of 208 patients with salivary stones and those of 208
      control patients were reviewed. Of the patients diagnosed with salivary stones,
      the submandibular gland was affected in 85.6% of the patients, the parotid gland
      in 9.6%, and the sublingual gland in 2.4% of the patients. None of the recorded
      systemic diseases was more prevalent in patients with salivary stones. Patients
      with salivary stones used significantly more antibiotics compared with the
      control group (P = .037). No significant differences were observed for other
      types of medication. There was no correlation between salivary stone formation,
      smoking, and alcohol consumption. CONCLUSIONS: The present study suggested that
      systemic diseases, medication, smoking, and alcohol consumption play no or only a
      limited role in the onset of salivary stones.

PMID- 25753449
TI  - The risk of acute kidney injury with transjugular intrahepatic portosystemic
      shunts.
AB  - Transjugular intrahepatic portosystemic shunts (TIPS) have been used for almost
      40 years as a safe and effective alternative to surgical shunts, mostly in the
      setting of portal hypertension. Well described procedural complications include
      hepatic encephalopathy, hemorrhage, liver infarction and failure. The risk of
      post procedural acute kidney injury (AKI) associated with intraprocedural
      intravenous contrast administration has not been evaluated. Using a retrospective
      chart review of all consecutive patients undergoing a TIPS procedure as part of
      routine clinical care between 2001 and 2011, we examined whether the volume of
      administered intravenous contrast was associated with AKI. Of 163 patients who
      had a TIPS procedure, 16% developed AKI as defined by a 0.3 mg/dl increase in
      serum creatinine within 48 h of the procedure. In adjusted analysis, a 50 ml
      increase of intravenous contrast was associated with a 1.27 (95% CI 1.01-1.60), p
      = 0.04 increased risk of AKI. Baseline serum creatinine was also associated with
      post procedural AKI; a 0.1 mg/dl increase in creatinine was associated with a
      1.17 (1.04-1.31), p = 0.008 risk. In patients with underlying kidney dysfunction,
      a 50 ml increase of intravenous contrast was associated with a 1.63 (1.20-2.31),
      p = 0.003 adjusted risk of AKI. In conclusion, intravenous contrast administered
      during a TIPS procedure is associated with an increased risk of AKI, particularly
      in patients with impaired renal function at baseline.

PMID- 25753451
TI  - Elucidating Reasons for Resident Underutilization of Electronic Adverse Event
      Reporting.
AB  - Reasons for resident underutilization of adverse event (AE) reporting systems are
      unclear, particularly given frequent resident exposure to AEs and near misses
      (NMs). Residents at an academic medical center were surveyed about AEs/NMs,
      barriers to reporting, patient safety climate, and educational interventions. A
      total of 350 of 527 eligible residents (66%) completed the survey; 77% of
      respondents reported involvement in an AE/NM, though only 43% had used the
      reporting system. Top barriers to reporting were not knowing what or how to
      report. Surgeons reported more than other residents (surgery, 61%; medical, 38%;
      hospital-based, 15%; P < .01), yet more often felt that systems were unlikely to
      change after reporting (surgery, 49%; medical, 28%; hospital-based. 18%; P <
      .01). Residents preferred discussions with supervisors (52%) and department-led
      conferences (46%) to increased reporting. Efforts to increase resident reporting
      should address common barriers to reporting as well as department-specific
      differences in resident knowledge, perceptions of system effectiveness, and
      educational preferences.

PMID- 25753450
TI  - The presence and impact of diastolic dysfunction on physical function and body
      composition in hemodialysis patients.
AB  - BACKGROUND: Cardiovascular (CV) diseases are the main cause of death in
      maintenance hemodialysis (MHD) patients. Muscle wasting and physical function
      decline are common in MHD patients, and significantly impair their quality of
      life. These can result from abnormalities in cardiac function, which can be
      further worsened by physical deconditioning. Left ventricular diastolic function
      parameters were recently shown to be a better predictor of exercise capacity than
      systolic measures in patients with CV complications. But little is known about
      the relationship between cardiac function and physical function in MHD patients.
      METHODS: In 82 MHD patients, left ventricular systolic dysfunction (LVSD) was
      assessed by ejection fraction and fractional shortening with echocardiography,
      and left ventricular diastolic dysfunction (LVDD) was assessed by pulse wave and
      tissue Doppler indices. Physical function was assessed by gait speed, performance
      on a shuttle walk test, and leg muscle strength. Dual-emission X-ray
      absorptiometry (DXA) was used to measure whole body lean mass (WBLM). RESULTS:
      The prevalence of LVDD and LVSD was 48.8 and 12.2%, respectively. Gait speed,
      shuttle walk time, leg strength, and WBLM% were significantly higher in the group
      without LVDD than with LVDD (p < 0.05 for all). However, there was no significant
      difference in any measure of physical function or body composition between
      patients with and without LVSD. CONCLUSION: These data suggest that LVDD is more
      closely related to physical function and body composition than LVSD in MHD
      patients, and hence that LVDD may be an important therapeutic target.

PMID- 25753452
TI  - A Cross-Sectional Analysis of Publication Types in Quality Improvement Journals.
AB  - Despite widespread engagement in quality improvement activities, little is known
      about the designs of studies currently published in quality improvement journals.
      This study's goal is to establish the prevalence of the types of research
      conducted in articles published in journals dedicated to quality improvement. A
      cross-sectional analysis was performed of 145 research articles published in 11
      quality improvement journals in 2011. The majority of study designs were
      considered pre-experimental (95%), with a small percentage of quasi-experimental
      and experimental designs. Of the studies that reported the results of an
      intervention (n = 60), the most common research designs were pre-post studies
      (33%) and case studies (25%). There were few randomized controlled trials or
      quasi-experimental study designs (12% of intervention studies). These results
      suggest that there are opportunities for increased use of quasi-experimental
      study designs.

PMID- 25753454
TI  - Dengue epidemiology in selected endemic countries: factors influencing expansion
      factors as estimates of underreporting.
AB  - OBJECTIVE: Dengue fever is globally considered underestimated. This study
      provides expansion factors (EFs) for dengue endemic selected countries and
      highlights critical issues in the use of EFs. METHODS: We identified dengue
      epidemiological cohort studies from 2000 to July 2013 through a literature search
      using PubMed, Web of Science and Lilacs (Latin American and Caribbean Health
      Sciences Database), pre-defined keywords and inclusion/exclusion criteria, and
      included Brazil, Colombia, Nicaragua, Peru, Puerto Rico, Venezuela, Bangladesh,
      Cambodia, India, Indonesia, Philippines, Singapore, Sri Lanka, Thailand and
      Vietnam. Dengue national and local passive surveillance data were derived from
      WHO regional websites, PAHO, SEARO and WPRO. EFs were calculated as CI cohort
      studies/CI passive data for both national and local levels. RESULTS: Cohort
      studies differed in case definition, laboratory test used and surveillance
      methods. The information on SEARO, PAHO and WPRO websites differed in terms of
      dengue epidemiological variables, population denominators and completeness. The
      highest incidence was reported by PAHO countries followed by WPRO and SEARO
      countries. EFs may vary for the different variables and denominators used for
      calculation. EFs were the highest in SEARO countries and lowest in PAHO
      countries. A trend for lower local EFs was observed. CONCLUSIONS: The use of EFs
      for quantifying dengue underreporting may be problematic due to lack of
      uniformity in reporting dengue both active and passive surveillance data. Quality
      dengue surveillance data are urgently needed for a better estimate of dengue
      disease burden and to measure the impact of preventive intervention.

PMID- 25753453
TI  - Automated Communication Tools and Computer-Based Medication Reconciliation to
      Decrease Hospital Discharge Medication Errors.
AB  - This study sought to determine the effects of automated primary care physician
      (PCP) communication and patient safety tools, including computerized discharge
      medication reconciliation, on discharge medication errors and posthospitalization
      patient outcomes, using a pre-post quasi-experimental study design, in
      hospitalized medical patients with >=2 comorbidities and >=5 chronic medications,
      at a single center. The primary outcome was discharge medication errors, compared
      before and after rollout of these tools. Secondary outcomes were 30-day
      rehospitalization, emergency department visit, and PCP follow-up visit rates.
      This study found that discharge medication errors were lower post intervention
      (odds ratio = 0.57; 95% confidence interval = 0.44-0.74; P < .001). Clinically
      important errors, with the potential for serious or life-threatening harm, and 30
      day patient outcomes were not significantly different between study periods.
      Thus, automated health system-based communication and patient safety tools,
      including computerized discharge medication reconciliation, decreased hospital
      discharge medication errors in medically complex patients.

PMID- 25753455
TI  - Final frontier.

PMID- 25753456
TI  - Removal of restrictions following primary THA with posterolateral approach does
      not increase the risk of early dislocation.
AB  - BACKGROUND AND PURPOSE: Patient education and mobilization restrictions are often
      used in an attempt to reduce the risk of dislocation following primary THA. To
      date, there have been no studies investigating the safety of removal of
      mobilization restrictions following THA performed using a posterolateral
      approach. In this retrospective non-inferiority study, we investigated the rate
      of early dislocation following primary THA in an unselected patient cohort before
      and after removal of postoperative mobilization restrictions. PATIENTS AND
      METHODS: From the Danish National Health Registry, we identified patients with
      early dislocation in 2 consecutive and unselected cohorts of patients who
      received primary THA at our institution from 2004 through 2008 (n = 946) and from
      2010 through 2014 (n = 1,329). Patients in the first cohort were mobilized with
      functional restrictions following primary THA whereas patients in the second
      cohort were allowed unrestricted mobilization. Risk of early dislocation (within
      90 days) was compared in the 2 groups and odds ratio (OR)-adjusted for possible
      confounders-was calculated. Reasons for early dislocation in the 2 groups were
      identified. RESULTS: When we adjusted for potential confounders, we found no
      increased risk of early dislocation within 90 days in patients who were mobilized
      without restrictions. Risk of dislocation within 90 days was lower (3.4% vs
      2.8%), risk of dislocation within 30 days was lower (2.1% vs 2.0%), and risk of
      multiple dislocations (1.8% vs 1.1%) was lower in patients who were mobilized
      without restrictions, but not statistically significantly so. Increasing age was
      an independent risk factor for dislocation. INTERPRETATION: Removal of
      mobilization restrictions from the mobilization protocol following primary THA
      performed with a posterolateral approach did not lead to an increased risk of
      dislocation within 90 days.

PMID- 25753457
TI  - Apathy and striatal dopamine transporter levels in de-novo, untreated Parkinson's
      disease patients.
AB  - INTRODUCTION: Apathy is a neuropsychiatric symptom in Parkinson's Disease (PD)
      which has a negative impact on quality of life and might be related in part to
      damage of presynaptic dopaminergic system. Little is known about relationship
      between striatal dopamine levels and apathy in PD patients without dementia
      and/or depression. The aim of the present study was to investigate the
      relationship between "pure apathy" and striatal dopamine uptake in untreated,
      drug-naive PD patients without clinically significant dementia and/or depression.
      METHODS: Fourteen PD patients with pure apathy and 14 PD patients without apathy,
      matched for age, side of motor symptoms at onset, motor disability and disease
      duration, underwent both neuropsychological and behavioral examination including
      self-rated version of the Apathy Evaluation Scale (AES-S). All patients underwent
      123 I-FP-CIT (DaT-SCAN) SPECT to assess dopamine transporter (DAT) striatal
      uptake. RESULTS: PD patients with apathy showed lower DAT levels in the striatum
      than non-apathetic patients. After Bonferroni correction the difference between
      groups was significant in the right caudate. CONCLUSIONS: Apathy is associated
      with reduced striatal dopamine transporter levels, independent of motor
      disability and depression in non-demented PD patients. These findings suggest
      that dysfunction of dopaminergic innervation in the striatum and particularly in
      the right caudate may contribute to development of apathy in early PD.

PMID- 25753458
TI  - Dopaminergic denervation severity depends on COMT Val158Met polymorphism in
      Parkinson's disease.
AB  - BACKGROUND: Catecholamine-O-methyl-tranferase (COMT) initiates dopamine
      degradation. Its activity is mainly determined by a single nucleotide
      polymorphism in the COMT gene (Val158Met, rs4680) separating high (Val/Val,
      COMT(HH)), intermediate (Val/Met, COMT(HL)) and low metabolizers (Met/Met,
      COMT(LL)). We investigated dopaminergic denervation in the striatum in PD
      patients according to COMT rs4680 genotype. METHODS: Patients with idiopathic PD
      were assessed for motor severity (UPDRS-III rating scale in OFF-state),
      dopaminergic denervation using [123I]-FP-CIT SPECT imaging, and genotyped for the
      COMT rs4680 enzyme. [123I]-FP-CIT binding potential (BP) for each voxel was
      defined by the ratio of tracer-binding in the region of interest (striatum,
      caudate nucleus and putamen) to that in a region of non-specific activity.
      Genotyping was performed using TaqMan((r)) SNP genotyping assay. We used a
      regression model to evaluate the effect of COMT genotype on the BP in the
      striatum and its sub-regions. RESULTS: Genotype distribution was: 11 (27.5%)
      COMT(HH), 26 (65%) COMT(HL) and 3 (7.5%) COMT(LL). There were no significant
      differences in disease severity, treatments, or motor scores between genotypes.
      When adjusted to clinical severity, gender and age, low and intermediate
      metabolizers showed significantly higher rates of striatal denervation
      (COMT(HL+LL) BP = 1.32 +/- 0.04) than high metabolizers (COMT(HH), BP = 1.6 +/-
      0.08; F(1.34) = 9.0, p = 0.005). Striatal sub-regions showed similar results. BP
      and UPDRS-III motor scores (r = 0.44, p = 0.04) (p < 0.001) were highly
      correlated. There was a gender effect, but no gender-genotype interaction.
      CONCLUSIONS: Striatal denervation differs according to COMT-Val158Met
      polymorphism. COMT activity may play a role as a compensatory mechanism in PD
      motor symptoms.

PMID- 25753460
TI  - Robust focus measure operator using adaptive log-polar mapping for three
      dimensional shape recovery.
AB  - Shape from focus (SFF) is a passive optical technique that reconstructs object
      shape from a sequence of image taken at different focus levels. In SFF
      techniques, computing focus measurement for each pixel in the image sequence,
      through a focus measure operator, is the fundamental step. Commonly used focus
      measure operators compute focus quality in Cartesian space and suffer from
      erroneous focus quality and lack in robustness. Thus, they provide erroneous
      depth maps. In this paper, we introduce a new focus measure operator that
      computes focus quality in log-polar transform (LPT) Properties of LPT, such as
      biological inspiration, data selection, and edge invariance, enable computation
      of better focus quality in the presence of noise. Moreover, instead of using a
      fixed patch of the image, we suggest the use of an adaptive window. The focus
      quality is assessed by computing variation in LPT. The effectiveness of the
      proposed technique is evaluated by conducting experiments using image sequences
      of different simulated and real objects. The comparative analysis shows that the
      proposed method is robust and effective in the presence of various types of
      noise. 

PMID- 25753459
TI  - Azide-rich peptides via an on-resin diazotransfer reaction.
AB  - Azide-containing amino acids are valuable building blocks in peptide chemistry,
      because azides are robust partners in several bioorthogonal reactions. Replacing
      polar amino acids with apolar, azide-containing amino acids in solid-phase
      peptide synthesis can be tricky, especially when multiple azide residues are to
      be introduced in the amino acid sequence. We present a strategy for effectively
      incorporating multiple azide-containing residues site-specifically.

PMID- 25753461
TI  - Let's go outside: using photography to explore values and culture in mental
      health nursing.
AB  - Creative and imaginative approaches to mental healthcare education are known to
      help students explore emotions, empathy and others' experiences, as well as
      address ambivalence and ambiguity. Very few studies in mental health nursing
      education specifically utilise photography as a participatory pedagogic tool,
      with even fewer utilising photography to explore understandings of culture,
      values and diversity. Photography makes visible complex, collaborative forms of
      learning and previously unidentified, unarticulated ideas about culture and
      values. Photography as a critical pedagogic method helps develop critical,
      politicized understandings of culture and values. Increasing culturally diverse
      populations means complex and conflicting values have become a common feature in
      mental health nursing. In education the need to critically examine such topics
      necessitates creative and engaging pedagogy, and visual methods are readily
      acknowledged as such. Yet while many studies advocate and demonstrate the value
      of art-based methods in student learning, very few studies in mental health
      nursing specifically utilize photography as a participatory pedagogic tool, and
      fewer still use photography to explore understandings of culture, values and
      diversity. In this paper, we discuss a qualitative study where mental health
      nursing students used photography to create images in order to explore their own
      and often dominant culture and attendant values. Findings suggest that
      photography makes visible situated, relational and collaborative learning, and
      surfaces previously unidentified, unarticulated ideas about culture and values.
      These practices mimic important processes central to mental health nursing
      practice and contemporaneous understandings of diverse cultures. We argue that
      photography provides an important resource with which to unearth subjugated
      knowledge, promote critical understandings of culture and values, and thereby
      help address inequalities in mental health care.

PMID- 25753462
TI  - Prenatal exposure to environmental chemical contaminants and asthma and eczema in
      school-age children.
AB  - BACKGROUND: Emerging evidence suggests that prenatal or early-life exposures to
      environmental contaminants may contribute to an increased risk of asthma and
      allergies in children. We aimed to the explore associations of prenatal exposures
      to a large set of environmental chemical contaminants with asthma and eczema in
      school-age children. METHODS: We studied 1024 mother-child pairs from Greenland
      and Ukraine from the INUENDO birth cohort. Data were collected by means of an
      interview-based questionnaire when the children were 5-9 years of age. Questions
      from the ISAAC study were used to define asthma, eczema, and wheeze. We applied
      principal components analysis (PCA) to sixteen contaminants in maternal serum
      sampled during pregnancy, including perfluoroalkyl substances (PFASs),
      metabolites of diethylhexyl (DEHP) and diisononyl (DiNP) phthalates, PCB-153, and
      p,p'-DDE. Scores of five principal components (PCs) explaining 70% of the
      variance were included in multiple logistic regression models. RESULTS: In a meta
      analysis that included both populations, the PC2 score, reflecting exposure to
      DiNP, was negatively associated with current eczema (OR 0.71, 95% CI 0.52-0.96).
      Other associations were not consistent between the two populations. In Ukrainian
      children, the PC3 score (DEHP) was positively associated with current wheeze
      (adjusted OR 1.56, 95% CI 1.03-2.37), whereas the PC5 score, dominated by
      perfluorooctanoic acid (PFOA), was inversely associated with current wheeze (OR
      0.64, 0.41-0.99). In Greenlandic children, a negative association of PC4
      (organochlorines) with ever eczema (OR 0.78, 0.61-0.99) was found. CONCLUSIONS:
      We found limited evidence to support a link between prenatal exposure to
      environmental chemical contaminants and childhood asthma and eczema.

PMID- 25753464
TI  - Intrauterine hypoechoic mass cephalad to cesarean scar pregnancy.

PMID- 25753463
TI  - Telocytes in minor salivary glands of primary Sjogren's syndrome: association
      with the extent of inflammation and ectopic lymphoid neogenesis.
AB  - It has been recently reported that telocytes, a stromal (interstitial) cell
      subset involved in the control of local tissue homeostasis, are hampered in the
      target organs of inflammatory/autoimmune disorders. Since no data concerning
      telocytes in minor salivary glands (MSGs) are currently available, aim of the
      study was to evaluate telocyte distribution in MSGs with normal architecture, non
      specific chronic sialadenitis (NSCS) and primary Sjogren's syndrome (pSS)-focal
      lymphocytic sialadenitis. Twelve patients with pSS and 16 sicca non-pSS subjects
      were enrolled in the study. MSGs were evaluated by haematoxylin and eosin
      staining and immunofluorescence for CD3/CD20 and CD21 to assess focus score,
      Tarpley biopsy score, T/B cell segregation and germinal center (GC)-like
      structures. Telocytes were identified by immunoperoxidase-based
      immunohistochemistry for CD34 and CD34/platelet-derived growth factor receptor
      alpha double immunofluorescence. Telocytes were numerous in the stromal
      compartment of normal MSGs, where their long cytoplasmic processes surrounded
      vessels and encircled both the excretory ducts and the secretory units. In NSCS,
      despite the presence of a certain degree of inflammation, telocytes were normally
      represented. Conversely, telocytes were markedly reduced in MSGs from pSS
      patients compared to normal and NSCS MSGs. Such a decrease was associated with
      both worsening of glandular inflammation and progression of ectopic lymphoid
      neogenesis, periductal telocytes being reduced in the presence of smaller
      inflammatory foci and completely absent in the presence of GC-like structures.
      Our findings suggest that a loss of MSG telocytes might have important
      pathophysiological implications in pSS. The specific pro-inflammatory cytokine
      milieu of pSS MSGs might be one of the causes of telocyte loss. 

PMID- 25753465
TI  - Simple extraction method using syringe filter for detection of ethephon in
      tomatoes by negative-ion mode liquid chromatography with tandem mass
      spectrometry.
AB  - In this study, a simple, rapid, and sensitive method was developed for the
      extraction of ethephon from homogenized tomatoes that does not require a cleanup
      procedure. In a syringe filter, three distinct layers - aqueous, acetonitrile,
      and n-hexane - are clearly separated after storage at -80  degrees C for 5-10
      min. A Dionex IonPac column was used to separate the analyte before detection
      using negative-ion mode liquid chromatography with tandem mass spectrometry
      (LC/MS/MS). The matrix effect of the tested analyte was negligibly small and the
      matched calibration showed a good linearity over a concentration range of 0.01
      1.0 mg/kg with a correlation coefficient (R(2) ) of 0.9998. The recovery at three
      fortification levels (0.1, 0.5 and 1.0 mg/kg) was between 82.9 and 108.6% with
      relative standard deviations (RSDs) <5.0%. The limit of quantification (0.03
      mg/kg) was lower than the maximum residue limit (3 mg/kg) set by the Ministry of
      Food and Drug Safety, Republic of Korea. From a field trial, the method developed
      herein was applied to calculate the decline pattern and predict the pre-harvest
      residue limits of ethephon in tomatoes. In conclusion, the proposed sample
      preparation is feasible for the detection of hydrophilic analytes in tomatoes.

PMID- 25753466
TI  - Analysis of BAG3 plasma concentrations in patients with acutely decompensated
      heart failure.
AB  - BACKGROUND: BCL-2-associated athanogene 3 (BAG3) is a protein implicated in the
      cardiomyocyte stress response and genesis of cardiomyopathy. Extracellular BAG3
      is measurable in patients with heart failure (HF), but the relationship of BAG3
      with HF prognosis is unclear. METHODS: BAG3 plasma concentrations were measured
      in 39 acutely decompensated HF patients; the primary endpoint was death at 1
      year. Baseline characteristics were compared by vital status and median BAG3
      concentration. Correlation of BAG3 with left ventricular ejection fraction (LVEF)
      and other biomarkers was performed. Prognostic value was assessed using Cox
      proportional hazards regression and Kaplan-Meier analysis. RESULTS: At baseline,
      median BAG3 was significantly higher in decedents (N=11) than survivors (N=28;
      1489 ng/mL versus 50 ng/mL; P=0.04); decedents also had worse renal function and
      higher median natriuretic peptide (NP) and sST2. BAG3 was not significantly
      correlated with NPs, mid-regional pro-adrenomedullin, sST2, or eGFR, however.
      Mortality was increased in patients with supra-median BAG3 (>336 ng/mL; 42.1%
      versus 15.0%, P=0.06). In age and LVEF-adjusted Cox proportional hazards, BAG3
      remained a significant mortality predictor (HR=3.20; 95% CI=1.34-7.65; P=0.02);
      those with supra-median BAG3 had significantly shorter time-to-death (P=0.04).
      CONCLUSION: The stress response protein BAG3 is measurable in patients with ADHF
      and may be prognostic for death.

PMID- 25753467
TI  - Task analysis of information technology-mediated medication management in
      outpatient care.
AB  - AIMS: Educating physicians in the procedural as well as cognitive skills of
      information technology (IT)-mediated medication management could be one of the
      missing links for the improvement of patient safety. We aimed to compose a
      framework of tasks that need to be addressed to optimize medication management in
      outpatient care. METHODS: Formal task analysis: decomposition of a complex task
      into a set of subtasks. First, we obtained a general description of the
      medication management process from exploratory interviews. Secondly, we
      interviewed experts in-depth to further define tasks and subtasks. SETTING:
      Outpatient care in different fields of medicine in six teaching and academic
      medical centres in the Netherlands and the United States. PARTICIPANTS: 20
      experts. Tasks were divided up into procedural, cognitive and macrocognitive
      tasks and categorized into the three components of dynamic decision making.
      RESULTS: The medication management process consists of three components: (i)
      reviewing the medication situation; (ii) composing a treatment plan; and (iii)
      accomplishing and communicating a treatment and surveillance plan. Subtasks
      include multiple cognitive tasks such as composing a list of current medications
      and evaluating the reliability of sources, and procedural tasks such as
      documenting current medication. The identified macrocognitive tasks were:
      planning, integration of IT in workflow, managing uncertainties and
      responsibilities, and problem detection. CONCLUSIONS: All identified procedural,
      cognitive and macrocognitive skills should be included when designing education
      for IT-mediated medication management. The resulting framework supports the
      design of educational interventions to improve IT-mediated medication management
      in outpatient care.

PMID- 25753468
TI  - Plasma renin activity is a strong and independent prognostic indicator in
      patients with acute decompensated heart failure treated with renin-angiotensin
      system inhibitors.
AB  - BACKGROUND: The renin-angiotensin system (RAS) is activated in heart failure (HF)
      as a compensatory mechanism, being related to cardiac remodeling and poor
      prognosis. Although RAS inhibitors are used as first-line drugs for HF, plasma
      renin activity (PRA) is upregulated by RAS inhibitors via a negative feedback
      mechanism. The clinical significance of PRA during RAS inhibitor therapy is
      poorly understood in acute decompensated HF (ADHF). Therefore we examined the
      impact of PRA in HF patients already receiving RAS inhibitors. METHODS AND
      RESULTS: Of 611 consecutive patients with ADHF and emergency admission to
      hospital, we studied the impact of PRA on the prognosis of ADHF in 293 patients
      already receiving RAS inhibitors before admission. The patients were divided into
      2 groups according to median PRA (>= vs. <3.4 ng.ml(-1).h(-1)). During a mean
      follow-up of 29.0 months, there were 124 deaths from all causes. Kaplan-Meier
      analysis showed that all-cause and cardiovascular mortality were significantly
      higher in patients with high PRA than low PRA (log-rank P=0.0002 and P<0.0001,
      respectively). Log PRA was an independent predictor of all-cause and
      cardiovascular death (HR, 1.194; 95% CI: 1.378-2.678, P<0.0001; and HR, 2.559;
      95% CI: 1.610-4.144, P<0.0001, respectively). CONCLUSIONS: PRA was associated
      with an increased risk of all-cause and cardiovascular mortality in ADHF patients
      already receiving RAS inhibitors, suggesting that PRA would be a useful biomarker
      during ADHF treatment.

PMID- 25753469
TI  - Predicting short-term mortality in advanced decompensated heart failure - role of
      the updated acute decompensated heart failure/N-terminal pro-B-type natriuretic
      Peptide risk score.
AB  - BACKGROUND: The first few months after admission are the most vulnerable period
      in patients with acute decompensated heart failure (ADHF). METHODS AND RESULTS:
      We assessed the association of the updated ADHF/N-terminal pro-B-type natriuretic
      peptide (NT-proBNP) risk score with 90-day and in-hospital mortality in 701
      patients admitted with advanced ADHF, defined as severe symptoms of worsening HF,
      severely depressed left ventricular ejection fraction, and the need for i.v.
      diuretic and/or inotropic drugs. A total of 15.7% of the patients died within 90
      days of admission and 5.2% underwent ventricular assist device (VAD) implantation
      or urgent heart transplantation (UHT). The C-statistic of the ADHF/NT-proBNP risk
      score for 90-day mortality was 0.810 (95% CI: 0.769-0.852). Predicted and
      observed mortality rates were in close agreement. When the composite outcome of
      death/VAD/UHT at 90 days was considered, the C-statistic decreased to 0.741.
      During hospitalization, 7.6% of the patients died. The C-statistic for in
      hospital mortality was 0.815 (95% CI: 0.761-0.868) and Hosmer-Lemeshow
      chi(2)=3.71 (P=0.716). The updated ADHF/NT-proBNP risk score outperformed the
      Acute Decompensated Heart Failure National Registry, the Organized Program to
      Initiate Lifesaving Treatment in Patients Hospitalized for Heart Failure, and the
      American Heart Association Get with the Guidelines Program predictive models.
      CONCLUSIONS: Updated ADHF/NT-proBNP risk score is a valuable tool for predicting
      short-term mortality in severe ADHF, outperforming existing inpatient predictive
      models.

PMID- 25753470
TI  - Late outcome of tricuspid annuloplasty using a flexible band/ring for functional
      tricuspid regurgitation.
AB  - BACKGROUND: We assessed late outcome after tricuspid annuloplasty (TAP) using a
      flexible band or ring for functional tricuspid regurgitation (FTR). METHODS AND
      RESULTS: We reviewed 220 consecutive patients (mean age, 65.4+/-11.4 years) who
      underwent TAP for FTR during mitral valve surgery between January 2000 and
      December 2010. Indications for TAP included the following: (1) TR grade greater
      than mild; (2) history of right heart failure; (3) atrial fibrillation; and (4)
      systolic pulmonary artery pressure (SPAP) >=50 mmHg. The mean follow-up period
      was 4.4+/-2.6 years. Overall hospital mortality was 5.5% (12/220). The 5- and 10
      year survival rates were 90.2+/-2.1% and 82.4+/-5.6%, respectively. Freedom from
      recurrent TR at 8 years was 78.0+/-6.6%. Twenty patients had a greater than mild
      TR grade at final follow-up. Elevated SPAP was a predictor of recurrent TR
      (hazard ratio, 1.091; P=0.0003), which was associated with advanced age, atrial
      fibrillation, rheumatic etiology and preoperative TR grade. There was a
      significant difference in freedom from valve-related events between residual TR
      greater than mild and less than moderate (log-rank test, P=0.0464). Factors
      affecting residual TR were preoperative TR grade (OR, 7.368; P=0.0267) and mitral
      valve replacement (OR, 4.369; P=0.0402). CONCLUSIONS: Late outcome of TAP in the
      present series was acceptable. Late outcome can be improved by performing TAP
      before deterioration of TR.

PMID- 25753472
TI  - Delayed haemolytic transfusion reaction in adults with sickle cell disease: a 5
      year experience.
AB  - Delayed haemolytic transfusion reactions (DHTR) are potentially life-threatening
      complications in patients with sickle cell disease (SCD). Between 1 August 2008
      and 31 December 2013, 220 of 637 adult patients in our centre had at least one
      red blood cell (RBC) transfusion in 2158 separate transfusion episodes. Twenty
      three DHTR events occurred in 17 patients (13 female) including 15 HbSS, one HbSC
      and one HbSbeta(0) thalassaemia, equating to a DHTR rate of 7.7% of patients
      transfused. Mean interval from RBC transfusion to DHTR event was 10.1 +/- 5.4 d,
      and typical presenting features were fever, pain and haemoglobinuria. Twenty of
      the 23 (87.0%) DHTR episodes occurred following transfusion in the acute setting.
      Notably, 11/23 (47.8%) of DHTRs were not diagnosed at the time of the event, most
      were misdiagnosed as a vaso-occlusive crisis. 16/23 DHTRs had 'relative
      reticulocytopenia', which was more common in older patients. Seven of 23 episodes
      resulted in alloantibody formation, and three caused autoantibody formation.
      DHTRs are a severe but uncommon complication of RBC transfusion in SCD and remain
      poorly recognized, possibly because they mimic an acute painful crisis. Most of
      the DHTRs are triggered by RBC transfusion in the acute setting when patients are
      in an inflammatory state. 

PMID- 25753473
TI  - Prediction model for lymph node metastasis and recommendations for elective neck
      dissection in lip cancer.
AB  - INTRODUCTION: In patients with squamous cell carcinoma (SCC) of the lip,
      occurrence of lymph node metastasis (LNM) is more frequent than in other
      cutaneous head and neck SCCs. The aim of this study was to identify predictive
      factors for LNM in SCC of the lip and to establish a prediction model identifying
      patients at high LNM risk. MATERIALS AND METHODS: Tumor characteristics of 326
      patients with lip SCC were analyzed retrospectively to assess differences between
      the LNM group and controls. Using binary logistic and Cox regression analysis, a
      prediction model for LNM was calculated. RESULTS: Lymph node metastasis occurred
      in 26 (8%) patients. Regression analysis revealed tumor extent, tumor depth and
      grading as the most important factors in the correct classification of LNM in
      94.2% of patients. A prediction model taking tumor depth and grading into account
      allowed for stratification of patients into high and low risk groups (sensitivity
      92.3%, specificity 78.3%, negative predictive value 99.2%). CONCLUSIONS: Our new
      prediction model was able to identify patients with lip cancer who had a high
      risk of LNM with a good level of accuracy. This algorithm is easy to apply as
      part of the decision process for elective and selective lymph node dissection in
      SCC of the lip.

PMID- 25753471
TI  - Increased cortical synaptic activation of TrkB and downstream signaling markers
      in a mouse model of Down Syndrome.
AB  - Down Syndrome (DS), trisomy 21, is characterized by synaptic abnormalities and
      cognitive deficits throughout the lifespan and with development of Alzheimer's
      disease (AD) neuropathology and progressive cognitive decline in adults. Synaptic
      abnormalities are also present in the Ts65Dn mouse model of DS, but which
      synapses are affected and the mechanisms underlying synaptic dysfunction are
      unknown. Here we show marked increases in the levels and activation status of
      TrkB and associated signaling proteins in cortical synapses in Ts65Dn mice.
      Proteomic analysis at the single synapse level of resolution using array
      tomography (AT) uncovered increased colocalization of activated TrkB with
      signaling endosome related proteins, and demonstrated increased TrkB signaling.
      The extent of increases in TrkB signaling differed in each of the cortical layers
      examined and with respect to the type of synapse, with the most marked increases
      seen in inhibitory synapses. These findings are evidence of markedly abnormal
      TrkB-mediated signaling in synapses. They raise the possibility that dysregulated
      TrkB signaling contributes to synaptic dysfunction and cognitive deficits in DS. 

PMID- 25753474
TI  - Bone regeneration in critical-size calvarial defects using human dental pulp
      cells in an extracellular matrix-based scaffold.
AB  - The rat calvarial defect is an established model to evaluate craniofacial bone
      regeneration using cell-scaffold biocomplexes. Dental pulp harbors stem cells
      with significant osteogenic properties. Extracellular matrix (ECM)-like scaffolds
      simulate the environment that cells observe in vivo. In the present study, we
      evaluated the osteogenic effect of a biocomplex of human dental pulp cells and a
      hyaluronic-based hydrogel scaffold in calvarial defects of immunocompetent rats.
      Dental pulp cells at the 2nd passage were characterized by flow cytometry,
      osteodifferentiated ex vivo for 4 days and the whole population was encapsulated
      in the synthetic ECM matrix. Cell vitality was verified 24 h upon encapsulation.
      5 mm calvarial defects were created in 30 male rats and filled with the
      biocomplex, the scaffold alone, or left untreated. Histological evaluation at 8
      weeks showed incomplete bone regeneration in all groups. The scaffold was not
      fully degraded and entrapped cells were detected in it. Histomorphometry showed
      statistically significant superior new bone formation in the biocomplex-treated
      group, compared to the two other groups. The present study provides evidence that
      the whole population of human dental pulp cells can advance bone healing when
      transplanted in immunocompetent animals and highlights the importance of proper
      scaffold degradation in cell-driven bioengineering treatments. 

PMID- 25753475
TI  - An entry to vinylcyclopropane through palladium-catalyzed intramolecular
      cyclopropanation of alkenes with unstabilized allylic tosylhydrazones.
AB  - A diastereoselective Pd-catalyzed intramolecular cyclopropanation of alkenes with
      unstabilized allylic tosylhydrazones was developed. This methodology provides an
      efficient entry toward synthesis of the bicyclo[3.1.0] hexane system with an exo
      double bond, and sets the basis for future elaboration of more complex polycyclic
      motifs. 

PMID- 25753476
TI  - Interpretation of immunohistochemistry data of tumor should consider
      microenvironmental factors.
AB  - The influence of tumor surrounding microenvironment is often neglected when
      immunohistochemistry is performed to investigate tumor properties and search
      biomarkers of cancer. This study was designed to evaluate whether the influence
      of tumor microenvironment on biological features of tumor cells should be taken
      into account for interpretation of the immunohistochemistry data of tumor
      specimens. In this study, we showed an example by using three tumor cell lines
      (HeLa, WSU-HN6, and Tca83) to establish tumor-caused bone destruction models in
      nude mice and then to investigate the influence of bone marrow microenvironment
      (BMM) on biological features of tumor cells. Immunohistochemistry results showed
      that, compared with tumor cells located outside of BMM, tumor cells located
      inside of BMM presented huge differences in the expression of inflammation
      related proteins including tumor necrosis factor-alpha (TNF-alpha), TNF receptor
      associated factor protein-6 (TRAF-6), phosphorylated-NF-kappaB p65 (p-p65),
      interleukin (IL)-6 and IL-11, matrix metalloproteinases including MMP-1, MMP-2,
      MMP-9, and MMP-13; and osteogenesis-related proteins including runt-related
      transcription factor 2 (RUNX2), bone sialoprotein (BSP), and osteocalcin (OCN) in
      all the models. However, when we compared the cell line pair derived from
      different sites (outside and inside of BMM, respectively) of the same HeLa tumor
      sample by real-time PCR, Western blot, and immunocytochemistry, the differences
      aforementioned in tumor tissues were not found. In addition, we verified that
      normal human bone marrow could not cause the above changes detected in vivo. Our
      results suggested that tumor-modified microenvironment could give the new
      biological features of the invaded tumor cells. Therefore, we should consider the
      influence of the surrounding microenvironment on tumor cells when we analyze
      tumor properties using immunohistochemistry.

PMID- 25753477
TI  - Nuclear shape descriptors by automated morphometry may distinguish aggressive
      variants of squamous cell carcinoma from relatively benign skin proliferative
      lesions: a pilot study.
AB  - We evaluated whether degrees of dysplasia may be consistently accessed in an
      automatic fashion, using different kinds of non-melanoma skin cancer (NMSC) as a
      validatory model. Namely, we compared Bowen disease, actinic keratosis, basal
      cell carcinoma, low-grade squamous cell carcinoma, and invasive squamous cell
      carcinoma. We hypothesized that characterizing the shape of nuclei may be
      important to consistently diagnose the aggressiveness of a skin tumor. While
      basal cell carcinoma is comparatively relatively benign, management of squamous
      cell carcinoma is controversial because of its potential to recur and
      intraoperative dilemma regarding choice of the margin or the depth for the
      excision. We provide evidence here that progressive nuclear dysplasia may be
      automatically estimated through the thresholded images of skin cancer and
      quantitative parameters estimated to provide a quasi-quantitative data, which can
      thenceforth guide the management of the particular cancer. For circularity,
      averaging more than 2500 nuclei in each group estimated the means +/- SD as 0.8
      +/- 0.007 vs. 0.78 +/- 0.0063 vs. 0.42 +/- 0.014 vs. 0.63 +/- 0.02 vs. 0.51 +/-
      0.02 (F = 318063.56, p < 0.0001, one-way analyses of variance). The mean aspect
      ratios were (means +/- SD) 0.97 +/- 0.0014 vs. 0.95 +/- 0.002 vs. 0.38 +/- 0.018
      vs. 0.84 +/- 0.0035 vs. 0.74 +/- 0.019 (F = 1022631.931, p < 0.0001, one-way
      analyses of variance). The Feret diameters averaged over 2500 nuclei in each
      group were the following: 1 +/- 0.0001 vs. 0.9 +/- 0.002 vs. 5 +/- 0.031 vs. 1.5
      +/- 0.01 vs. 1.9 +/- 0.004 (F = 33105614.194, p < 0.0001, one-way analyses of
      variance). Multivariate analyses of composite parameters potentially detect
      aggressive variants of squamous cell carcinoma as the most dysplastic form, in
      comparison to locally occurring squamous cell carcinoma and basal cell carcinoma,
      or benign skin lesions.

PMID- 25753478
TI  - Malic enzyme 1 induces epithelial-mesenchymal transition and indicates poor
      prognosis in hepatocellular carcinoma.
AB  - Malic enzyme 1 (ME1) links the glycolytic and citric acid cycles and is important
      for NADPH production, glutamine metabolism, and lipogenesis. Recently, its
      deregulation has been implicated in the progression of various cancers. However,
      the role of ME1 in the progression of hepatocellular carcinoma (HCC) remains
      unclear. In this study, we utilized short hairpin RNA-mediated gene silencing to
      investigate the biological effects of ME1 depletion in HCC and determined its
      prognostic significance in HCC. ME1 expression was examined by real-time (RT)-PCR
      and Western blot using five HCC cell lines and one normal liver cell line. We
      used polyethylenimine nanoparticles to deliver a short hairpin RNA to induce
      cessation of ME1 expression in HCC cells. Changes in NADPH production and
      reactive oxygen species (ROS) production were studied. Metastatic potentials of
      HCC cells were evaluated in vitro. Furthermore, we evaluated the protein level of
      ME1 in para-tumor and cancerous tissues of 65 HCC patients with detailed
      clinical, pathological, and clinical follow-up data. Patients' survivals were
      further assessed as well. Upregulated ME1 expression was observed in HCC cell
      lines. Downregulation of ME1 attenuated NADPH production and stimulated ROS
      production. Silencing ME1 was noted to inhibit migratory and invasive properties
      of HCC cells by inducing the E-cadherin expression and decreasing of N-cadherin
      and vimentin expression in a ROS-dependent pathway. Overexpression of ME1 was
      observed in a major fraction of HCC samples. Higher level of ME1 in tumors was
      significantly associated with reduced overall survival (Kaplan-Meier analysis, P
      = 0.024) and reduced progression-free survival (Kaplan-Meier analysis, P =
      0.011). Inhibition of ME1 expression decreases HCC metastasis via suppression of
      epithelial-mesenchymal transition (EMT) processes in ROS-induced pathways. ME1
      overexpression associates with unfavorable prognoses in patients with HCC,
      suggesting that ME1 is a poor prognostic predictor of hepatocellular carcinoma.

PMID- 25753479
TI  - Effect of Prednisolone Administration on Patients with Unexplained Recurrent
      Miscarriage and in Routine Intracytoplasmic Sperm Injection: A Meta-Analysis.
AB  - The effects of prednisolone on pregnancy outcome are open to debate. This meta
      analysis was performed to evaluate the efficiency of prednisolone administration
      on unexplained recurrent miscarriage (RM) and the process of assisted
      reproductive technology (ART). Relevant publications were searched from databases
      and the included randomized controlled trials (RCTs) investigated effects of
      prednisolone administration in women with unexplained RM or during ART. The
      outcomes in our analysis were measured in terms of risk ratios (RRs) with 95%
      confidence intervals (CI) using random effect models. This meta-analysis was
      performed based on pregnancy outcomes following prednisolone treatment. This meta
      analysis provides evidence that prednisolone therapy improves pregnancy outcomes
      in women with idiopathic RM (live birth rate: RR 1.58, 95% CI 1.23-2.02;
      successful pregnancy outcome: RR 7.63, 95% CI 3.71-15.69; miscarriage rate: RR
      0.42, 95% CI 0.28-0.61). Our meta-analysis revealed a non-significant effect of
      prednisolone on pregnancy outcome during intracytoplasmic sperm injection (ICSI)
      cycles (pregnancy rate: RR 1.02, 95% CI 0.84-1.24; clinical pregnancy rate: RR
      1.01, 95% CI 0.82-1.24; implantation rate: RR 1.04, 95% CI 0.85-1.28).
      Prednisolone administration may improve pregnancy outcomes in women with
      idiopathic RM; its efficacy in women undergoing ICSI is not significant. 

PMID- 25753480
TI  - Visualization of synaptic domains in the Drosophila brain by magnetic resonance
      microscopy at 10 micron isotropic resolution.
AB  - Understanding the complex architecture, connectivity, and pathology of the human
      brain is a major application of magnetic resonance imaging (MRI). However, the
      cellular basis of MR signal is still poorly understood. The advent of MR
      microscopy (MRM) enables imaging biological samples at cellular resolution,
      helping to interpret the nature of MR signal at the cellular level. In this
      regard, the small Drosophila brain can reveal key aspects of MR signal through
      the visualization of complex, intact neuronal structures in their native spatial
      arrangement. Applying state-of-the-art MR technology, we imaged fixed Drosophila
      heads at 10 MUm isotropic resolution by two endogenously contrasted MRM
      sequences. The improved MRM sensitivity described here delivered the highest 3D
      resolution of an intact animal head reported so far. 3D fast low angle shot
      (FLASH) revealed strong signal in most internal tissues, particularly in the
      brain cortex, which contains the cell bodies of neurons and glia. Remarkably, 3D
      diffusion weighted imaging (DWI) delivered unprecedented contrast within the
      modular brain neuropil, revealing hyperintense signal in synapse-rich
      microdomains. Thus, the complex Drosophila brain revealed unknown features of
      FLASH and DWI with potential applications in characterizing the structure and
      pathology of the mammalian brain. 

PMID- 25753481
TI  - Initial experience of use of tolvaptan in critically ill patients with fluid
      overload.
AB  - WHAT IS KNOWN AND OBJECTIVE: Positive volume balance is related with high
      mortality in critically ill patients. We describe our experience in the use of
      tolvaptan in patients with fluid overload. CASE SUMMARY: Six patients in the
      recovery phase from septic shock were included. All patients achieved an increase
      in diuresis after the first day, with a median fluid balance variation of -2362 (
      485 to -3447) mL. At the end of treatment, median fluid balance variation was 
      9080 (-26,784 to -4395) mL. WHAT IS NEW AND CONCLUSION: Tolvaptan could be an
      option in critically ill patients with fluid overload and resistant or not
      treatable with conventional diuretics.

PMID- 25753482
TI  - On combining Thole's induced point dipole model with fixed charge distributions
      in molecular mechanics force fields.
AB  - The Thole induced point dipole model is combined with three different point
      charge fitting methods, Merz-Kollman (MK), charges from electrostatic potentials
      using a grid (CHELPG), and restrained electrostatic potential (RESP), and two
      multipole algorithms, distributed multipole analysis (DMA) and Gaussian multipole
      model (GMM), which can be used to describe the electrostatic potential (ESP)
      around molecules in molecular mechanics force fields. This is done to study how
      the different methods perform when intramolecular polarizability contributions
      are self-consistently removed from the fitting done in the force field
      parametrization. It is demonstrated that the polarizable versions of the partial
      charge models provide a good compromise between accuracy and computational
      efficiency in describing the ESP of small organic molecules undergoing
      conformational changes. For the point charge models, the inclusion of
      polarizability reduced the the average root mean square error of ESP over the
      test set by 4-10%.

PMID- 25753483
TI  - Enhanced HIV-1 Reverse Transcriptase Inhibitory and Antibacterial Properties in
      Callus of Catha edulis Forsk.
AB  - Developing tissue culture systems for medicinal plants is important in that they
      may offer an alternative to protect wild populations. However, analysis of
      bioactivity for tissue culture developed plant tissues is required to offer
      support and allow acceptance in traditional medicine. The use of propagated
      callus could provide potential material for therapeutic purposes. This study was
      aimed at evaluating the anti-HIV and antibacterial properties of a three-month
      old tissue culture-derived calli and leaves of cultivated mother plants of Catha
      edulis Forsk. The calli were derived from leaf explants using different plant
      growth regulators. The calli obtained from callus cultured on 9.8 MUM indole-3
      butyric acid plus 2.7 MUM naphthalene acetic acid exhibited the highest HIV-1
      reverse transcriptase inhibitory effects when compared with other treatments and
      the mother plants. Different extracts of callus exhibited high antibacterial
      activity (<1 mg/mL: minimum inhibitory concentration from 0.098 to 0.78 mg/mL)
      against both gram-positive and gram-negative bacteria. Leaf acetone extracts
      showed moderate activity (minimum inhibitory concentration of 0.78 mg/mL) against
      Staphylococcus aureus. The present study indicated that tissue culture-derived
      calli could be used as therapeutic agents for traditional medicine. The choice of
      treatment used in the tissue culture system and the age of the callus for
      production of biomass may significantly influence its therapeutic potential.

PMID- 25753485
TI  - Intracellular fluorescent temperature probe based on triarylboron substituted
      poly N-isopropylacrylamide and energy transfer.
AB  - A novel hydrophilic fluorescence temperature probe (PNDP) based on polarity
      sensitive triarylboron compound (DPTB) and PNIPAM is designed and synthesized. In
      order to overcome the shortcomings of the single-intensity-based sensing
      mechanism and obtain more robust signals, ratiometric readout is achieved by
      designing an efficient FRET system (PNDP-NR) between DPTB and Nile Red (NR). PNDP
      NR possesses some excellent features, including wide temperature range, good
      linear relationship, high temperature resolution, excellent reversibility, and
      stability. Within a sensing temperature range of 30-55  degrees C, the
      fluorescence color of PNDP-NR experiences significant change from red to green
      blue. PNDP-NR is also introduced into NIH/3T3 cells to sense the temperature at
      the single-cell level. It gave excellent photostability and low cytotoxicity in
      vivo. 

PMID- 25753484
TI  - Neuron-specific antioxidant OXR1 extends survival of a mouse model of amyotrophic
      lateral sclerosis.
AB  - Amyotrophic lateral sclerosis is a devastating neurodegenerative disorder
      characterized by the progressive loss of spinal motor neurons. While the
      aetiological mechanisms underlying the disease remain poorly understood,
      oxidative stress is a central component of amyotrophic lateral sclerosis and
      contributes to motor neuron injury. Recently, oxidation resistance 1 (OXR1) has
      emerged as a critical regulator of neuronal survival in response to oxidative
      stress, and is upregulated in the spinal cord of patients with amyotrophic
      lateral sclerosis. Here, we tested the hypothesis that OXR1 is a key
      neuroprotective factor during amyotrophic lateral sclerosis pathogenesis by
      crossing a new transgenic mouse line that overexpresses OXR1 in neurons with the
      SOD1(G93A) mouse model of amyotrophic lateral sclerosis. Interestingly, we report
      that overexpression of OXR1 significantly extends survival, improves motor
      deficits, and delays pathology in the spinal cord and in muscles of SOD1(G93A)
      mice. Furthermore, we find that overexpression of OXR1 in neurons significantly
      delays non-cell-autonomous neuroinflammatory response, classic complement system
      activation, and STAT3 activation through transcriptomic analysis of spinal cords
      of SOD1(G93A) mice. Taken together, these data identify OXR1 as the first neuron
      specific antioxidant modulator of pathogenesis and disease progression in SOD1
      mediated amyotrophic lateral sclerosis, and suggest that OXR1 may serve as a
      novel target for future therapeutic strategies. 

PMID- 25753486
TI  - De novo biosynthesis of cytokinins in the biotrophic fungus Claviceps purpurea.
AB  - Disease symptoms of some phytopathogenic fungi are associated with changes in
      cytokinin (CK) levels. Here, we show that the CK profile of ergot-infected rye
      plants is also altered, although no pronounced changes occur in the expression of
      the host plant's CK biosynthesis genes. Instead, we demonstrate a clearly
      different mechanism: we report on the first fungal de novo CK biosynthesis genes,
      prove their functions and constitute a biosynthetic pathway. The ergot fungus
      Claviceps purpurea produces substantial quantities of CKs in culture and, like
      plants, expresses enzymes containing the isopentenyltransferase and lonely guy
      domains necessary for de novo isopentenyladenine production. Uniquely, two of
      these domains are combined in one bifunctional enzyme, CpIPT-LOG, depicting a
      novel and potent mechanism for CK production. The fungus also forms trans-zeatin,
      a reaction catalysed by a CK-specific cytochrome P450 monooxygenase, which is
      encoded by cpp450 forming a small cluster with cpipt-log. Deletion of cpipt-log
      and cpp450 did not affect virulence of the fungus, but Deltacpp450 mutants
      exhibit a hyper-sporulating phenotype, implying that CKs are environmental
      factors influencing fungal development. 

PMID- 25753487
TI  - The prevalence of medical reasons for non-participation in the Scottish breast
      and bowel cancer screening programmes.
AB  - OBJECTIVE: Increasing uptake of cancer screening is a priority for health systems
      internationally, however, some patients may not attend because they are
      undergoing active treatment for the cancer of interest or have other medical
      reasons that mean participation would be inappropriate. This study aims to
      quantify the proportion of non-participants who have a medical reason for not
      attending cancer screening. METHODS: Medical reasons for not participating in
      breast and bowel screening were defined a priori on the basis of a literature
      review and expert opinion. The notes of 700 patients at two GP practices in
      Scotland were reviewed, to ascertain the prevalence of medical reasons amongst
      non-participants. Simple proportions and confidence intervals were calculated.
      RESULTS: 17.4% of breast and 2.3% of bowel screening non-participants had a
      medical reason to not participate. The two most common reasons were previous
      breast cancer follow up (8.86%) and recent mammogram (6.57%). CONCLUSION: These
      patients may not benefit from screening while also being distressed by receiving
      an invitation. This issue also makes accurate monitoring and target-setting for
      improving uptake difficult. Further work is needed to estimate robustly the
      extent to which medical reasons account for screening non-participation in a
      larger population.

PMID- 25753488
TI  - Efficacy and safety of linagliptin in Asian patients with type 2 diabetes
      mellitus inadequately controlled by metformin: A multinational 24-week,
      randomized clinical trial.
AB  - BACKGROUND: Despite the increasing prevalence of type 2 diabetes mellitus (T2DM)
      in Asia, clinical trials for glucose-lowering therapies are often dominated by
      Caucasian and/or Western populations. The present Phase III randomized placebo
      controlled double-blind, 24-week study evaluated the efficacy and safety of the
      dipeptidyl peptidase-4 inhibitor linagliptin added to metformin in Asian T2DM
      patients. METHODS: In all, 306 patients (n = 265 Chinese; n = 24 Malaysian; n =
      17 Filipino), aged 18-80 years with HbA1c between >=7.0 and <=10.0% and on
      metformin therapy were randomized (2:1) to either linagliptin 5 mg daily or
      placebo added to metformin. Antidiabetes drugs other than metformin were washed
      out prior to randomization. The primary endpoint was change in mean HbA1c from
      baseline after 24 weeks. RESULTS: Baseline characteristics were well-matched
      between the groups (overall mean [+/-SD] HbA1c 8.0 +/- 0.8%). Adjusted mean (+/
      SE) HbA1c decreased in the linagliptin and placebo groups by -0.66 +/- 0.05 and 
      0.14 +/- 0.07%, respectively (placebo-corrected difference -0.52 +/- 0.09%; 95%
      confidence interval [CI] -0.70, -0.34; P < 0.0001). In patients with baseline
      HbA1c >=8.5%, the placebo-corrected decrease in HbA1c was -0.89 +/- 0.17% (P <
      0.0001). Adverse events occurred in similar proportions in the linagliptin and
      placebo patients (27.3% and 28.0%, respectively) and few were considered drug
      related (2.4% and 0.0%, respectively). Hypoglycemia occurred in 1.0% of patients
      in both groups. Linagliptin therapy was weight neutral. CONCLUSIONS: Linagliptin
      5 mg was efficacious and well tolerated over 24 weeks in Asian patients with T2DM
      inadequately controlled by metformin.

PMID- 25753489
TI  - Exploring Carers' Judgements of Responsibility and Control in Response to the
      Challenging Behaviour of People with Intellectual Disabilities.
AB  - BACKGROUND: This study examines Weiner's recent cognitive emotional model which
      makes a distinction between judgements of control and responsibility and
      emphasizes the moderation of control by 'mitigating' factors. METHOD: In response
      to four vignettes describing two conditions of control (high or low) and
      mitigating factors (present or absent), questionnaires rating judgements of
      responsibility and emotional responses (anger and sympathy) were completed by 52
      care staff. RESULTS: Analysis of the data for sympathy demonstrated that
      attributions of control were moderated by communication ability and that the
      effect of control upon sympathy was mediated by the judgement of responsibility.
      CONCLUSIONS: The data offer tentative support Weiner's account of the mitigation
      of control attributions in making responsibility judgements and their subsequent
      effects on emotional responses. Implications for research and clinical work are
      discussed.

PMID- 25753490
TI  - Evaluation of ammonia-nitrogen removal efficiency from aqueous solutions by
      ultrasonic irradiation in short sonication periods.
AB  - In this study, mechanisms and efficiency of ammonia-nitrogen removal from aqueous
      solutions by ultrasonic irradiation were investigated. Depending on the factors
      affecting the sonication (initial concentration, initial pH, ultrasonic power
      density and sonication period), sonication tests were carried out and ammonium
      nitrogen removal efficiency by ultrasonic irradiation was determined. In these
      experiments, ammonia-nitrogen removal efficiency was achieved in the range of 8
      64%. In short sonication periods, the best ammonia-nitrogen removal efficiency
      was achieved at pH 8.2-11. Lower ammonia-nitrogen removal efficiency was observed
      in high initial ammonia-nitrogen concentration of solutions. It was observed that
      high initial ammonia-nitrogen concentrations may led to decreased ammonia
      nitrogen removal efficiency however quantity of ammonia-nitrogen removal was
      higher. Because high initial concentration had a negative impact on the
      sonochemical reactions the heat of cavitation bubbles was reduced. Ammonia
      nitrogen removal efficiency was increased with ultrasonic density and sonication
      period. This study showed that effective ammonia-nitrogen removal could be
      achieved by the ultrasonic irradiation in short sonication periods (as 60-600 s).
      Specific cost of ammonia-nitrogen removal by the ultrasonic irradiation from
      simulated ground water, surface water, wastewater and landfill leachate was also
      calculated. The specific removal cost was varied between 0.01 and 0.25$/g ammonia
      nitrogen.

PMID- 25753491
TI  - Development and validation of an efficient ultrasound assisted extraction of
      phenolic compounds from flax (Linum usitatissimum L.) seeds.
AB  - Flaxseed accumulates in its seedcoat a macromolecular complex composed of lignan
      (secoisolariciresinol diglucoside, SDG), flavonol (herbacetin diglucoside, HDG)
      and hydroxycinnamic acids (p-couramic, caffeic and ferulic acid glucosides).
      Their antioxidant and/or cancer chemopreventive properties support their interest
      in human health and therefore, the demand for their extraction. In the present
      study, ultrasound-assisted extraction (UAE) of flaxseed phenolic compounds was
      investigated. Scanning Electron Microscopy imaging and histochemical analysis
      revealed the deep alteration of the seedcoat ultrastructure and the release of
      the mucilage following ultrasound treatment. Therefore, this method was found to
      be very efficient for the reduction of mucilage entrapment of flaxseed phenolics.
      The optimal conditions for UAE phenolic compounds extraction from flaxseeds were
      found to be: water as solvent supplemented with 0.2N of sodium hydroxide for
      alkaline hydrolysis of the SDG-HMG complex, an extraction time of 60 min at a
      temperature of 25 degrees C and an ultrasound frequency of 30 kHz. Under these
      optimized and validated conditions, highest yields of SDG, HDG and
      hydroxycinnamic acid glucosides were detected in comparison to other published
      methods. Therefore, the procedure presented herein is a valuable method for
      efficient extraction and quantification of the main flaxseed phenolics. Moreover,
      this UAE is of particular interest within the context of green chemistry in terms
      of reducing energy consumption and valuation of flaxseed cakes as by-products
      resulting from the production of flax oil.

PMID- 25753492
TI  - A pilot study on temporal changes in IL-1beta and TNF-alpha serum levels after
      spinal cord injury: the serum level of TNF-alpha in acute SCI patients as a
      possible marker for neurological remission.
AB  - STUDY DESIGN: Serum levels of interleukin-1beta (IL-1beta) and tumour necrosis
      factor-alpha (TNF-alpha) were measured over a 12-week period in 23 patients with
      spinal cord injury (SCI) with and without neurological improvement. OBJECTIVES:
      To determine the course of IL-1beta and TNF-alpha in patients with SCI and
      observe a possible relationship between improvements in neurological functioning
      and cytokine levels. SETTING: All patients were treated at the BG Trauma Centre,
      Ludwigshafen, Germany. All lab work was done at the University Hospital,
      Heidelberg. METHODS: Spinal cord injury was classified according to the American
      Spinal Injury Association (ASIA) impairment scale (AIS) in 23 patients. TNF-alpha
      and IL-1beta levels were measured upon arrival at the hospital, after 4 h, 9 h
      and 12 h, on days 1 and 3 and at the end of weeks 1, 2, 4, 8 and 12. RESULTS:
      Temporal changes in TNF-alpha and IL-1beta in SCI patients were seen. Patients
      with AIS improvement (Group 1) had significantly lower TNF-alpha levels at 9 h
      compared with patients without AIS improvement (Group 2; P<0.01). The course of
      IL-1beta fluctuated greatly between 4 h and week 1 in the groups; however,
      between 2 and 12 weeks post trauma, there was an overall decline in both groups.
      CONCLUSION: Measuring serum levels of TNF-alpha and IL-1beta over time could be
      useful in tracking the course of SCI. Our data show differences in measured
      cytokines over a 12-week period for SCI patients with and without neurological
      improvement.

PMID- 25753494
TI  - Bedside prediction of the progress of pressure ulcer healing in patients with
      spinal cord injury using the 'Decu-stick'.
AB  - STUDY DESIGN: This is a prospective cohort study. OBJECTIVES: The objective of
      this study was to predict the progress of healing of pressure ulcers (PUs) in
      spinal cord injury (SCI) patients after the first 4 weeks. SETTING: The study was
      conducted in a specialized SCI rehabilitation unit in The Netherlands. METHODS:
      Weekly measurements of length, width and depth/undermining of grades II-IV PUs
      under sacrum or ischial tuberosity in SCI patients with the 'Decu-stick' were
      taken. The speed of reduction of the greatest dimension in the first 4 weeks of
      the granulation-epithelization (G-E) phase was compared with the speed of
      reduction of this dimension after week 4 until the end of observation. RESULTS:
      Fifty-one PUs in 45 patients were measured. During the first 4 weeks of the G-E
      phase, the greatest dimension of 23/51 PUs reduced with a speed of ?0.5 cm per
      week. In 22 of these 23 PUs, this speed remained ?0.5 from week 4 until the end
      of observation (weeks 5-22). Closure: 21 patients (pts); operation: 2 pts. Of
      28/51 PUs, this dimension reduced with <0.5 cm per week. In 27/28 PUs, this speed
      remained <0.5 from week 4 until the end of observation (weeks 9-37). Closure: 6
      pts; operation: 16 pts; discharge with open ulcer: 6 pts. CONCLUSION: Measurement
      of PUs in SCI patients with the 'Decu-stick' provides a reliable, quick, cheap
      and easy-to-learn bedside method to predict the progress of healing in PUs in SCI
      patients after 4 weeks of conservative treatment with a positive predictive value
      of 0.95 and an negative predictive value of 0.96. This provides a scientific
      basis for the decision on operative or alternative conservative treatment.

PMID- 25753493
TI  - The effect of alpha-lipoic acid (ALA) supplementation on cardiovascular risk
      factors in men with chronic spinal cord injury: a clinical trial.
AB  - STUDY DESIGN: A randomized, double-blind, placebo-controlled clinical trial.
      OBJECTIVE: To assess the effect of alpha-lipoic acid (ALA) supplementation on IL
      6, hs-CRP, FBS, anthropometric indices, food intake and blood pressure in male
      patients with chronic spinal cord injury (SCI). SETTING: Imam Khomeini Hospital,
      Tehran University of Medical Sciences, Tehran, Iran. METHODS: Fifty-eight men
      with chronic SCI participated in the study. Participants were divided in two
      groups: one group received 600 mg of supplemental ALA (n=28) and the other group
      received placebo (n=30) for 12 weeks. At the beginning and end of the study,
      biochemical parameters, anthropometric indices, blood pressure and dietary
      intakes were measured. Dietary intake was measured using N4 software, and
      statistical analyses were carried out using SPSS16. RESULTS: No significant
      reduction was found in IL-6 (P=0.97) and hs-CRP levels (P=0.23). There was
      significant reduction in fasting blood sugar (P=0.001), body weight (P=0.001),
      BMI (P=0.001), waist circumference (P=0.001) and blood pressure (P=0.001).
      Dietary intake was significantly reduced, including fat (P=0.001), carbohydrate
      (P=0.001), protein (P=0.002) and energy intakes (P=0.001). CONCLUSION: Lipoic
      acid supplementation had no significant effect on the measured inflammatory
      markers but it reduces fasting blood sugar, anthropometric parameters, food
      intake and blood pressure in men with chronic SCI.

PMID- 25753495
TI  - The Influence of High-Impact Exercise on Cortical and Trabecular Bone Mineral
      Content and 3D Distribution Across the Proximal Femur in Older Men: A Randomized
      Controlled Unilateral Intervention.
AB  - Regular exercisers have lower fracture risk, despite modest effects of exercise
      on bone mineral content (BMC). Exercise may produce localized cortical and
      trabecular bone changes that affect bone strength independently of BMC. We
      previously demonstrated that brief, daily unilateral hopping exercises increased
      femoral neck BMC in the exercise leg versus the control leg of older men. This
      study evaluated the effects of these exercises on cortical and trabecular bone
      and its 3D distribution across the proximal femur, using clinical CT. Fifty
      healthy men had pelvic CT scans before and after the exercise intervention. We
      used hip QCT analysis to quantify BMC in traditional regions of interest and
      estimate biomechanical variables. Cortical bone mapping localized cortical mass
      surface density and endocortical trabecular density changes across each proximal
      femur, which involved registration to a canonical proximal femur model. Following
      statistical parametric mapping, we visualized and quantified statistically
      significant changes of variables over time in both legs, and significant
      differences between legs. Thirty-four men aged mean (SD) 70 (4) years exercised
      for 12-months, attending 92% of prescribed sessions. In traditional regions of
      interest, cortical and trabecular BMC increased over time in both legs. Cortical
      BMC at the trochanter increased more in the exercise than control leg, whereas
      femoral neck buckling ratio declined more in the exercise than control leg.
      Across the entire proximal femur, cortical mass surface density increased
      significantly with exercise (2.7%; p < 0.001), with larger changes (> 6%) at
      anterior and posterior aspects of the femoral neck and anterior shaft.
      Endocortical trabecular density also increased (6.4%; p < 0.001), with localized
      changes of > 12% at the anterior femoral neck, trochanter, and inferior femoral
      head. Odd impact exercise increased cortical mass surface density and
      endocortical trabecular density, at regions that may be important to structural
      integrity. These exercise-induced changes were localized rather than being evenly
      distributed across the proximal femur.

PMID- 25753496
TI  - Analysis of the lateral geniculate nucleus in dichromatic and trichromatic
      marmosets.
AB  - Marmosets are diurnal New World monkeys that show sex-linked cone photopigment
      polymorphism, whereby all males and some females are dichromats ("red-green
      colorblind"), but most females show trichromatic color vision. Here we asked
      whether trichromats express chromatic-specific circuitry in the lateral
      geniculate nucleus (LGN). The volume of parvocellular (P), magnocellular (M), and
      koniocellular (K) layers was calculated in Nissl-stained sections from the LGN of
      adult marmosets (Callithrix jacchus; 10 trichromatic females; 2 dichromatic
      females; and 13 dichromatic males). Retinal ganglion cell axon terminals within
      the P and K layers were reconstructed and measured following anterograde tracer
      (dextran) injections. We show that there is little difference in LGN layer volume
      with respect to age, weight, or sex of the animals, or between dichromatic and
      trichromatic phenotypes. The morphology of retinal ganglion cell terminals was
      largely indistinguishable on comparing dichromats and trichromats, and likewise
      on comparing terminals representing peripheral or foveal retina. We conclude that
      the LGN circuits we studied are largely independent of red-green color vision
      phenotype and visual field location.

PMID- 25753497
TI  - Primary well-differentiated liposarcoma of the eyelid clinically masquerading as
      a benign tumour: a rare entity confirmed by murine double minute 2 fluorescence
      in-situ hybridization.

PMID- 25753498
TI  - Compliance with osteoporosis medications - an underestimated determinant of anti
      fracture efficacy.

PMID- 25753499
TI  - Marion Downs: Her life and legacy (1914-2014).

PMID- 25753500
TI  - Phantom scatter corrections of radiochromic films in high-energy brachytherapy
      dosimetry: a Monte Carlo study.
AB  - Our aim in this study was to calculate Monte Carlo-based phantom scatter
      corrections of various radiochromic films for different solid phantoms for high
      energy brachytherapy sources. Brachytherapy sources (60)Co, (137)Cs, (192)Ir, and
      (169)Yb and radiochromic films EBT, EBT2 (lot 020609 and lot 031109), RTQA, XRT,
      XRQA, and HS were investigated in this study. The solid phantom materials
      investigated were PMMA (polymethylmethacrylate), polystyrene, solid water,
      virtual water, plastic water, RW1, RW3, A150, and WE210. Monte Carlo-based user
      codes DOSRZnrc and FLURZnrc of the EGSnrc code system were employed in the
      present work. For the (60)Co source, the polystyrene, plastic water, solid water,
      virtual water, RW1, RW3, and WE210 phantoms were water equivalent for the
      investigated films, but showed distance-dependent values for XRT and XRQA films.
      For the (137)Cs and (192)Ir sources, the solid water, virtual water, RW1, RW3,
      and WE210 phantoms were water equivalent for the investigated films, but showed
      distance-dependent values for XRT and XRQA films. For these sources, the
      remaining phantoms showed distance-dependent values for all of the films
      investigated. For the (169)Yb source, all of the investigated phantoms showed
      distance-dependent values for the investigated films. This study suggests that
      radiochromic films demonstrate distance-dependent values, but the degree of
      dependence is related to the types of solid phantom and film. Hence, for
      brachytherapy dosimetry involving radiochromic films and solid phantom materials,
      phantom scatter corrections need to be applied. 

PMID- 25753501
TI  - Pleural puncture that excludes the ablation zone decreases the risk of
      pneumothorax after percutaneous microwave ablation in porcine lung.
AB  - PURPOSE: To test the hypothesis that the geometry of probe placement with respect
      to the pleural puncture site affects the risk of pneumothorax after microwave
      (MW) ablation in the lung. MATERIALS AND METHODS: Computed tomography-guided MW
      ablation of the lung was performed in 8 swine under general anesthesia and
      mechanical ventilation. The orientation of the 17-gauge probe was either
      perpendicular (90 degrees ) or parallel (< 30 degrees ) with respect to the
      pleural puncture site, and the ablation power was 30 W or 65 W for 5 minutes.
      After MW ablation, swine were euthanized, and histopathologic changes were
      assessed. Frequency and factors affecting pneumothorax were evaluated by
      multivariate analysis. RESULTS: Among 62 lung MW ablations, 13 (21%)
      pneumothoraces occurred. No statistically significant difference was noted in the
      rate of pneumothorax between the perpendicular and the parallel orientations of
      the probe (31% vs 14%; odds ratio [OR], 2.8; P = .11). The pneumothorax rate was
      equal for 65-W and 30-W ablation powers (21% and 21%; OR, 1.0; P = .94). Under
      multivariate analysis, 2 factors were independent positive predictors of
      pneumothorax: ablation zone inclusive of pleural insertion point (OR, 7.7; P =
      .02) and time since intubation (hours) (OR, 2.7; P = .02). CONCLUSIONS:
      Geometries where the pleural puncture site excluded the ablation zone decreased
      pneumothorax in swine undergoing MW ablation in the lung. Treatment planning to
      ensure that the pleural puncture site excludes the subsequent ablation zone may
      reduce the rate of pneumothorax in patients undergoing MW ablation in the lung.

PMID- 25753502
TI  - Echocardiographic measurements in normal chinese adults focusing on cardiac
      chambers and great arteries: a prospective, nationwide, and multicenter study.
AB  - BACKGROUND: Currently available echocardiographic reference values are derived
      mainly from North American and European population studies, and no
      echocardiographic reference values are available for the Chinese population. The
      aim of this study was to establish normal values of echocardiographic
      measurements of the cardiac chambers and great arteries in a nationwide,
      population-based cohort of healthy Han Chinese adults. METHODS: A total of 1,586
      healthy Han Chinese volunteers aged 18 to 79 years were screened at 43
      collaborating laboratories throughout China. Standard M-mode and two-dimensional
      echocardiography was performed to obtain measurements of the cardiac chambers and
      great arteries. The impacts of gender and age on all echocardiographic
      measurements were analyzed. RESULTS: A total of 1,394 qualified healthy subjects
      (mean age, 47.3 +/- 16.0 years; 678 men) were ultimately enrolled. Except for
      left ventricular ejection fraction, values of cardiac chamber and great arterial
      dimensions were significantly higher in men than in women. Most measurements of
      the atrial and great arterial dimensions, left ventricular wall thickness, and
      left ventricular mass increased with age in both men and women. CONCLUSIONS:
      Normal reference values of cardiac dimensional parameters were established for
      the first time in a nationwide, population-based cohort of healthy Han Chinese
      adults. Because most of these parameters were found to vary with gender and age,
      reference values stratified for gender and age should be used in clinical
      practice.

PMID- 25753504
TI  - Surveying the hidden attitudes of hospital nurses' towards poverty.
AB  - AIMS AND OBJECTIVES: To explore the attitudes held by registered nurses about
      persons living in poverty. BACKGROUND: As a profession, nursing has strong
      commitment to advocating for the socioeconomically disadvantaged. The links among
      poverty and health disparities are well established and research demonstrates
      that attitudes of providers can influence how those in poverty use health
      services. Although nurses are the largest sector of healthcare providers
      globally, little research has been published on their attitudes towards patients
      they care for who live in poverty. DESIGN: Cross-sectional survey. METHODS: Used
      a convenience sample of 117 registered nurses who completed the Attitudes Towards
      Poverty Short Form that contained three subscales. Regression analysis was used
      to examine the associations between the nurses' age, education, and years of
      experience, political views and financial security with their total score and
      subscale scores. RESULTS: Nurses were more likely to agree with stigmatising
      statements than statements that attributed poverty to personal deficiency or
      structural factors. In the multivariate analysis, years of experience were
      associated with more positive attitudes towards those living in poverty. Nurses
      with the most experience had less stigmatising beliefs about poverty and were
      more likely to endorse structural explanations. Those with a baccalaureate
      education were also more likely to endorse structural explanations for poverty.
      CONCLUSIONS: Gaining knowledge about attitudes towards and the factors
      influencing those attitudes, for example, education, are important in helping
      combat the disparities associated with poverty. RELEVANCE TO CLINICAL PRACTICE:
      Nurses have a duty to evaluate their individual attitudes and biases towards
      those living in poverty and how those attitudes and biases may influence daily
      practice. Assessing nurses' attitudes towards poverty may aid in better means of
      empowering nurses to seek solutions that will improve health conditions for those
      living in poverty.

PMID- 25753503
TI  - Right ventricular function in preterm and term neonates: reference values for
      right ventricle areas and fractional area of change.
AB  - BACKGROUND: Right ventricular (RV) fractional area of change (FAC) is a
      quantitative two-dimensional echocardiographic measurement of RV function. RV FAC
      expresses the percentage change in the RV chamber area between end-diastole (RV
      end-diastolic area [RVEDA]) to end-systole (RV end-systolic area [RVESA]). The
      objectives of this study were to determine the maturational (age- and weight
      related) changes in RV FAC and RV areas and to establish reference values in
      healthy preterm and term neonates. METHODS: A prospective longitudinal study was
      conducted in 115 preterm infants (23-28 weeks' gestational age at birth, 500
      1,500 g). RV FAC was measured at 24 hours of age, 72 hours of age, and 32 and 36
      weeks' postmenstrual age (PMA). The maturational patterns of RVEDA, RVESA, and RV
      FAC were compared with those in 60 healthy full-term infants in a cross-sectional
      study (>=37 weeks, 3.5 +/- 1 kg), who underwent echocardiography at birth (n =
      25) and 1 month of age (n = 35). RVEDA and RVESA were traced in the RV-focused
      apical four-chamber view, and FAC was calculated using the formula 100 * [(RVEDA 
      RVESA)/RVEDA)]. Premature infants who developed chronic lung disease or had
      clinically and hemodynamically significant patent ductus arteriosus were excluded
      (n = 55) from the reference values. Intra- and interobserver reproducibility
      analysis was performed. RESULTS: RV FAC ranged from 26% at birth to 35% by 36
      weeks' PMA in preterm infants (n = 60) and increased almost 2 times faster in the
      first month of age compared with healthy term infants (n = 60). Similarly, RVEDA
      and RVESA increased throughout maturation in both term and preterm infants. RV
      FAC and RV areas were correlated with weight (r = 0.81, P < .001) but were
      independent of gestational age at birth (r = 0.3, P = .45). RVEDA and RVESA were
      correlated with PMA in weeks (r = 0.81, P < .001). RV FAC trended lower in
      preterm infants with bronchopulmonary dysplasia (P = .04) but was not correlated
      with size of patent ductus arteriosus (P = .56). There was no difference in RV
      FAC based on gender or need for mechanical ventilation. CONCLUSIONS: This study
      establishes reference values of RV areas (RVEDA and RVESA) and RV FAC in healthy
      term and preterm infants and tracks their maturational changes during postnatal
      development. These measures increase from birth to 36 weeks' PMA, and this is
      reflective of the postnatal cardiac growth as a contributor to the maturation of
      cardiac function These measures are also linearly associated with increasing
      weight throughout maturation. This study suggests that two-dimensional RV FAC can
      be used as a complementary modality to assess global RV systolic function in
      neonates and facilitates its incorporation into clinical pediatric and neonatal
      guidelines.

PMID- 25753505
TI  - Exploration and exploitation of water in colloidal crystals.
AB  - Water on solid surfaces is ubiquitously found in nature, in most cases due to
      mere adsorption from ambient moisture. Because porous structures have large
      surfaces, water may significantly affect their characteristics. This is
      particularly obvious in systems formed by separate particles, whose interactions
      are strongly influenced by small amounts of liquid. Water/solid phenomena, like
      adsorption, condensation, capillary forces, or interparticle cohesion, have
      typically been studied at relatively large scales down to the microscale, like in
      wet granular media. However, much less is known about how water is confined and
      acts at the nanoscale, for example, in the interstices of divided systems,
      something of utmost importance in many areas of materials science nowadays. With
      novel approaches, in-depth investigations as to where and how water is placed in
      the nanometer-sized pores of self-assembled colloidal crystals have been made,
      which are employed as a well-defined, versatile model system with useful optical
      properties. In this Progress Report, knowledge gained in the last few years about
      water distribution in such nanoconfinements is gathered, along with how it can be
      controlled and the consequences it brings about to extract new or enhance
      existing material functionalities. New methods developed and new capabilities of
      standard techniques are described, and the water interplay with the optical,
      chemical, and mechanical properties of the ensemble are discussed. Some lines for
      applicability are also highlighted and aspects to be addressed in the near future
      are critically summarized. 

PMID- 25753506
TI  - Diffusion-weighted stimulated echo acquisition mode (DW-STEAM) MR spectroscopy to
      measure fat unsaturation in regions with low proton-density fat fraction.
AB  - PURPOSE: To propose and optimize diffusion-weighted stimulated echo acquisition
      mode (DW-STEAM) for measuring fat unsaturation in the presence of a strong water
      signal by suppressing the water signal based on a shorter T2 and higher
      diffusivity of water relative to fat. METHODS: A parameter study for point
      resolved spectroscopy (PRESS) and STEAM using oil phantoms was performed and
      correlated with gas chromatography (GC). Simulations of muscle tissue signal
      behavior using DW-STEAM and long-echo time (TE) PRESS and a parameter
      optimization for DW-STEAM were conducted. DW-STEAM and long-TE PRESS were applied
      in the gastrocnemius muscles of nine healthy subjects. RESULTS: STEAM with TE and
      mixing time (TM) up to 45 ms exhibited R(2) correlations above 0.98 with GC and
      little T2 -weighting and J-modulation for the quantified olefinic/methylene peak
      ratio. The optimal parameters for muscle tissue using DW-STEAM were b-value =
      1800 s/mm(2), TE = 33 ms, TM = 30 ms, and repetition time = 2300 ms. In vivo
      measured mean olefinic signal-to-noise ratios were 72 and 40, mean apparent
      olefinic water fractions were 0.19 and 0.11 for DW-STEAM and long-TE PRESS,
      respectively. CONCLUSION: Optimized DW-STEAM MR spectroscopy is superior to long
      TE PRESS for measuring fat unsaturation, if a strong water peak prevents the
      olefinic fat signal's quantification at shorter TEs and water's tissue specific
      ADC is substantially higher than fat.

PMID- 25753507
TI  - Interventions that may reduce depressive symptoms among prostate cancer patients:
      a systematic review and meta-analysis.
AB  - OBJECTIVE: Prostate cancer patients are at increased risk of depression yet there
      is no standard intervention to address this. The purpose of this meta-analysis is
      to examine the efficacy of interventions in reducing depressive symptoms in men
      with prostate cancer. METHODS: Searches for studies were conducted in four
      databases and by hand. Randomized controlled trials of any intervention relative
      to control for depression in prostate cancer patients at any stage of their
      cancer treatment were included. RESULTS: We identified 11 studies that randomized
      men with prostate cancer to either an intervention meant to improve some aspect
      of quality of life or control and reported depressive symptoms scores before and
      after the intervention or control condition. Two of these were not used in our
      meta-analysis either for concerns about quality or for lack of depression scores.
      The interventions identified in the remaining nine articles were exercise (four),
      information (three), psychotherapy or peer support (three), massage therapy
      (one), and medication (one). Several publications included more than one type of
      intervention. A meta-analysis of all studies showed that an intervention of some
      types significantly improved depressive symptom scores relative to the control
      condition (improvement in depression score by -0.86 unit (95% CI: -1.42, -0.31)).
      Isolating the peer support/psychotherapy studies also showed significant
      improvement (improvement in depression score by -1.09 unit (95% CI: -2.05, 
      0.13)). CONCLUSION: Treatments to improve depressive symptoms in men with
      prostate cancer may be effective, with the best evidence supporting the use of
      peer support/psychotherapy.

PMID- 25753508
TI  - Are pregnant women's obstetric care preferences contemplated in a provider
      dominated maternity care system?

PMID- 25753509
TI  - Effect of temporary and unemployed work on the risk of mortality.

PMID- 25753510
TI  - Response to Kawada T: Effect of temporary and unemployed work on the risk of
      mortality (Letter to the Editor, re: Khlat M et al. (2014): Mortality gradient
      across the labour market core-periphery structure: a 13-year mortality follow-up
      study in north-eastern France).

PMID- 25753511
TI  - Prevalence of IgG Antibodies to Toxoplasma gondii in Veterinary and Undergraduate
      Students at Virginia Tech, Blacksburg, Virginia.
AB  - Toxoplasma gondii is a globally distributed parasitic protozoan that infects
      humans and other warm-blooded vertebrates. Felids are the only definitive host
      for T. gondii, and they excrete oocysts in their faeces. The national prevalence
      in humans is declining in the United States. This zoonotic organism is of
      particular interest due to its importance in pregnant women, in individuals with
      altered immune systems, and in reactivated ocular infections. Exposure to the
      parasite in humans is usually associated with consumption of raw or undercooked
      meat or by accidental ingestion of oocysts. It was hypothesized that veterinary
      students would have a greater chance at exposure to the parasite than an average
      population of undergraduate students due to increased contact with cats who are
      infected. A commercially available ELISA was used to examine serum samples from
      336 students (252 veterinary students and 84 undergraduate students) at Virginia
      Polytechnic Institute and State University and the Virginia-Maryland Regional
      College of Veterinary Medicine for serum IgG antibodies to T. gondii antigen. The
      prevalence of T. gondii in these subjects was 5.6% in veterinary school students
      (n = 252) and 2.4% in undergraduates (n = 84). There was no significant
      difference (P > 0.05) in the prevalence of T. gondii antibodies in veterinary
      versus undergraduate students. The overall prevalence of 4.8% in all students in
      this study reflects the continuing decline of antibodies to T. gondii in humans
      in the United States.

PMID- 25753512
TI  - Traditional Chinese medicine education in Canada.
AB  - The history of education and legislation of traditional Chinese medicine (TCM)
      and acupuncture in Canada is short. The first school of TCM opened its door to
      the general public in Canada in 1985 and the first legislation of acupuncture was
      introduced in Alberta, Canada in 1988. Currently, TCM and/or acupuncture have
      been regulated in five provinces in Canada. The legislation and regulation, as
      well as education of TCM and acupuncture vary among the five provinces in Canada.
      Opportunities and challenges facing TCM education exist simultaneously.
      Strategies are proposed to develop an international standard for TCM education in
      Canada, and possibly in other English speaking countries as well. 

PMID- 25753513
TI  - Targeted agri-environment schemes significantly improve the population size of
      common farmland bumblebee species.
AB  - Changes in agricultural practice across Europe and North America have been
      associated with range contractions and local extinction of bumblebees (Bombus
      spp.). A number of agri-environment schemes have been implemented to halt and
      reverse these declines, predominantly revolving around the provision of
      additional forage plants. Although it has been demonstrated that these schemes
      can attract substantial numbers of foraging bumblebees, it remains unclear to
      what extent they actually increase bumblebee populations. We used standardized
      transect walks and molecular techniques to compare the size of bumblebee
      populations between Higher Level Stewardship (HLS) farms implementing pollinator
      friendly schemes and Entry Level Stewardship (ELS) control farms. Bumblebee
      abundance on the transect walks was significantly higher on HLS farms than ELS
      farms. Molecular analysis suggested maximum foraging ranges of 566 m for Bombus
      hortorum, 714 m for B. lapidarius, 363 m for B. pascuorum and 799 m for B.
      terrestris. Substantial differences in maximum foraging range were found within
      bumblebee species between farm types. Accounting for foraging range differences,
      B. hortorum (47 vs 13 nests/km(2) ) and B. lapidarius (45 vs 22 nests/km(2) )
      were found to nest at significantly greater densities on HLS farms than ELS
      farms. There were no significant differences between farm type for B. terrestris
      (88 vs 38 nests/km(2) ) and B. pascuorum (32 vs 39 nests/km(2) ). Across all
      bumblebee species, HLS management had a significantly positive effect on
      bumblebee nest density. These results show that targeted agri-environment schemes
      that increase the availability of suitable forage can significantly increase the
      size of wild bumblebee populations. 

PMID- 25753514
TI  - Triple combination treatment with fractional CO2 laser plus topical betamethasone
      solution and narrowband ultraviolet B for refractory vitiligo: a prospective,
      randomized half-body, comparative study.
AB  - Vitiligo on extremities and/or bony prominences is very resistant to treatment.
      Twenty-five patients with symmetrical and stable vitiligo on extremities and/or
      bony prominences were enrolled. The treatment side received fractional carbon
      dioxide laser followed by topical compound betamethasone solution and narrowband
      ultraviolet B phototherapy. The control side received laser treatment plus
      phototherapy. The result of treatment side showed that 44% patients achieved over
      50% re-pigmentation and patient satisfaction score was 5.12 +/- 3.23, higher than
      those of control (p < 0.05). Adverse events were slight and tolerable. The triple
      combination treatment could be used as an alternative modality for refractory
      vitiligo. 

PMID- 25753516
TI  - Ordered microporous layered lanthanide 1,3,5-benzenetriphosphonates pillared with
      cationic organic molecules.
AB  - Novel isomorphous pillared-layer-type crystalline lanthanide 1,3,5
      benzenetriphosphonates were prepared with bpy and dbo as organic pillars (LnBP
      bpy and LnBP-dbo; Ln: Ce, Pr, and Nd). Ab initio crystal structure solution using
      synchrotron X-ray powder diffraction data revealed that the organic pillars do
      not exist as neutral coordinating ligands but as cationic molecules. Especially
      the LnBP-dbo phases have ordered interlayer space filled with water molecules
      between the dbo pillars, and the interlayer water is successfully removed by
      heating under vacuum with slightly distorted but basically retained pillared
      layer structures. Microporosity of the materials is confirmed by adsorption of
      nitrogen, carbon dioxide, and hydrogen gases. Such microporous layered metal
      phosphonates pillared with cationic molecules should be unprecedented and should
      offer new strategies to design ordered microporous materials. 

PMID- 25753515
TI  - A Conserved Di-Basic Motif of Drosophila Crumbs Contributes to Efficient ER
      Export.
AB  - The Drosophila type I transmembrane protein Crumbs is an apical determinant
      required for the maintenance of apico-basal epithelial cell polarity. The level
      of Crumbs at the plasma membrane is crucial, but how it is regulated is poorly
      understood. In a genetic screen for regulators of Crumbs protein trafficking we
      identified Sar1, the core component of the coat protein complex II transport
      vesicles. sar1 mutant embryos show a reduced plasma membrane localization of
      Crumbs, a defect similar to that observed in haunted and ghost mutant embryos,
      which lack Sec23 and Sec24CD, respectively. By pulse-chase assays in Drosophila
      Schneider cells and analysis of protein transport kinetics based on
      Endoglycosidase H resistance we identified an RNKR motif in Crumbs, which
      contributes to efficient ER export. The motif identified fits the highly
      conserved di-basic RxKR motif and mediates interaction with Sar1. The RNKR motif
      is also required for plasma membrane delivery of transgene-encoded Crumbs in
      epithelial cells of Drosophila embryos. Our data are the first to show that a di
      basic motif acts as a signal for ER exit of a type I plasma membrane protein in a
      metazoan organism. 

PMID- 25753517
TI  - Isolated unilateral facial nerve palsy: an unusual manifestation of recurrent
      diffuse large B-cell lymphoma.

PMID- 25753518
TI  - Feeding practices in infancy associated with caries incidence in early childhood.
AB  - BACKGROUND: Early-life feeding behaviors foretell later dietary habits and health
      outcomes. Few studies have examined infant dietary patterns and caries occurrence
      prospectively. OBJECTIVE: Assess whether patterns in food and drink consumption
      before age 12 months are associated with caries incidence by preschool age.
      METHODS: We collected early-life feeding data within a birth cohort from low
      income families in Porto Alegre, Brazil. Three dietary indexes were defined,
      based on refined sugar content and/or previously reported caries associations: a
      count of sweet foods or drinks introduced <6-months (e.g., candy, cookies, soft
      drinks), a count of other, nonsweet items introduced <6-months (e.g., beans,
      meat), and a count of sweet items consumed at 12 months. Incidence of severe
      early childhood caries (S-ECC) at age 38 months (N = 458) was compared by score
      tertile on each index, adjusted for family, maternal, and child characteristics
      using regression modeling. RESULTS: Introduction to a greater number of
      presumably cariogenic items in infancy was positively associated with future
      caries. S-ECC incidence was highest in the uppermost tertile of the '6-month
      sweet index' (adjusted cumulative incidence ratio, RR, versus lowest tertile:
      1.46; 95% CI: 0.97, 2.04) and the uppermost tertile of the '12-month sweet index'
      (RR: 1.55; 95% CI: 1.17, 2.23). The association was specific for sweet items:
      caries incidence did not differ by tertile of the '6-month nonsweet index' (RR:
      1.00; 95% CI: 0.70, 1.40). Additionally, each one-unit increase on the 6-month
      and the 12-month sweet indexes, but not the 6-month nonsweet index, was
      statistically significantly associated with greater S-ECC incidence and
      associated with more decayed, missing, or restored teeth. Results were robust to
      minor changes in the items constituting each index and persisted if liquid items
      were excluded. CONCLUSIONS: Dietary factors observed before age 12-months were
      associated with S-ECC at preschool age, highlighting a need for timely,
      multilevel intervention.

PMID- 25753519
TI  - Limited proteolysis of fibrinogen by fibrinogenase from Echis multisquamatis
      venom.
AB  - Previously we purified fibrinogenase from venom of Echis multisquamatis and
      showed that the enzyme predominantly cleaves BbetaArg42-Ala43 peptide bond of
      fibrinogen. A much slower hydrolysis of its Aalpha-chain was also shown. To
      evaluate the accessibility of the hydrolysis sites to fibrinogenase's hydrolytic
      action, the pathway of cleavage of Aalpha- and Bbeta-chains of fibrinogen,
      monomeric and polymeric fibrin desA and desAB has been investigated using western
      blot with monoclonal antibodies to Bbeta 26-42 and Aalpha 20-78 of fibrinogen.
      The data indicated that the BbetaArg42-Ala43 peptide bond is available for
      cleavage in all forms of fibrin(ogen) with the exception of polymerized fibrin
      desAB. This is direct evidence of BbetaN-domain involvement in formation of
      protofibrils that makes it inaccessible to protease. The Aalpha-chain of
      fibrinogen remained intact after 3 min of incubation with fibrinogenase. Further
      incubation resulted in cleaving of the fibrin(ogen) alphaC-regions with the
      formation of two kinds of degradation products (~30 and ~60 kDa). In the case of
      monomeric fibrin desA or desAB we observed simultaneous hydrolysis of Aalpha and
      Bbeta-chains and the cleavage of Aalpha-chain was more apparent for both forms of
      polymeric fibrin.

PMID- 25753520
TI  - Dissecting alternative splicing in the formation of Miltenberger glycophorin
      subtype III (GYP.Mur).
AB  - BACKGROUND AND OBJECTIVES: Miltenberger subtype III (Mi.III, GP.Mur) is one of
      the most important red cell phenotypes in the fields of transfusion in South-East
      Asia. GP.Mur is believed to evolve from homologous gene recombination events
      between glycophorin A (GYPA) and glycophorin B (GYPB). GYP.Mur differs from GYPB
      in only seven nucleotides dispersed near the region of 3' exon 3 of GYP.Mur. The
      goal of this study was to dissect how these nucleotide variants affected splicing
      of exon 3. MATERIALS AND METHODS: We first designed two minigene constructs: one
      containing GYP.Mur from exon 2 to exon 4 and the other containing GYPB in the
      same region. To test how these nucleotide variations between GYP.Mur and GYPB
      affected the splicing, a repertoire of the GYP.Mur-like minigene constructs with
      different point mutations were created. These minigene variants were evaluated
      for their abilities to induce splicing of exon 3 using a heterologous expression
      system. RESULTS: (1) GYP.Mur minigene expressed exons 2, 3 and 4, whereas GYPB
      minigene expressed only exon 2 and exon 4. (2) The single nucleotide alteration
      at the position of the 5' splice site of glycophorin intron 3 reversed the
      splicing decision. (3) The nucleotide variations between GYP.Mur and GYPB other
      than that at the 5' splice site showed very little or no effect on splicing of
      exon 3. CONCLUSION: Splicing of the glycophorin B-A-B hybrids (GYP.Mur and
      GYP.BUN) and unsplicing of GYPB follow the GU-AG rule strictly.

PMID- 25753521
TI  - CD44-expressing undifferentiated carcinoma with rhabdoid features of the
      pancreas: molecular analysis of aggressive invasion and metastasis.
AB  - Carcinoma with rhabdoid features is a rare malignant tumor with a poor prognosis
      whose molecular mechanism for aggressive behavior is unclear. We describe an
      undifferentiated pancreatic carcinoma with rhabdoid features that demonstrated
      extensive invasion and metastasis. Examination of a 63-year-old man with back
      pain disclosed a retroperitoneal tumor with multiple metastases. Lymph node
      biopsy revealed an undifferentiated carcinoma of unknown origin. Intensive
      chemotherapy was ineffective; the patient died 3 months after initial symptoms.
      Autopsy showed that the tumor displaced the retroperitoneal space: it diffusely
      invaded and destroyed the pancreas and duodenum. Histology demonstrated tumor
      cells with eccentric vesicular nuclei, large nucleoli, juxtanuclear eosinophilic
      inclusions, and poor cell adhesion. Immunohistochemistry showed that tumor cells
      expressed cytokeratin and vimentin, and electron microscopy confirmed a
      perinuclear mass of intermediate fibrils and lipid droplets, which indicated an
      undifferentiated carcinoma with rhabdoid features. Tumor tissue contained
      hyaluronan; tumor cells strongly expressed CD44, matrix metalloproteinase-9,
      hypoxia-inducible factor-1alpha, hyaluronan synthase 2, and acyl-CoA:cholesterol
      acyltransferase 1 and had a high Ki-67(+) ratio. Since hyaluronan is a ligand for
      CD44, formation of CD44-hyaluronan complex on the cell surface activates CD44 and
      this activation may explain why the tumor manifested aggressive invasion and
      metastasis throughout the clinical course. 

PMID- 25753522
TI  - Polycystic kidney disease in Sprague-Dawley rats.
AB  - Polycystic kidney disease (PKD) is a cystic genetic disorder of the kidneys which
      is typically associated with cystic bile duct dilatation in the liver in humans,
      and domestic and laboratory animals. In humans, there are two types of PKD,
      autosomal dominant polycystic kidney disease (ADPKD) and autosomal recessive
      polycystic kidney disease (ARPKD). ADPKD is caused by mutations in PKD1 or PKD2
      gene while ARPKD is caused by mutation or loss of the PKHD1 (polycystic kidney
      and hepatic disease 1) gene. Here we report a morphologically confirmed case of
      spontaneous PKD in a Sprague-Dawley rat in which anatomic pathology examination
      revealed numerous cystic changes in the kidney and liver. Lesions consisted of
      marked cystic dilatations of renal tubules, and moderate cystic dilatations of
      intrahepatic bile ducts with portal fibrosis. We present detailed histologic
      features of the spontaneous PKD and compare them with disease model rats carrying
      an autosomal recessive PKHD 1 gene mutation. 

PMID- 25753523
TI  - Successful treatment of recalcitrant granulomatous rosacea with oral thalidomide
      and topical pimecrolimus.

PMID- 25753525
TI  - Mild Heat Treatment Primes Human CD34(+) Cord Blood Cells for Migration Toward
      SDF-1alpha and Enhances Engraftment in an NSG Mouse Model.
AB  - Simple efforts are needed to enhance cord blood (CB) transplantation. We
      hypothesized that short-term exposure of CD34(+) CB cells to 39.5 degrees C would
      enhance their response to stromal-derived factor-1 (SDF-1), by increasing lipid
      raft aggregation and CXCR4 expression, thus leading to enhanced engraftment. Mild
      hyperthermia (39.5 degrees C) significantly increased the percent of CD34(+) CB
      that migrated toward SDF-1. This was associated with increased expression of
      CXCR4 on the cells. Mechanistically, mild heating increased the percent of
      CD34(+) cells with aggregated lipid rafts and enhanced colocalization of CXCR4
      within lipid raft domains. Using methyl-beta-cyclodextrin (MbetaCD), an agent
      that blocks lipid raft aggregation, it was determined that this enhancement in
      chemotaxis was dependent upon lipid raft aggregation. Colocalization of Rac1, a
      GTPase crucial for cell migration and adhesion, with CXCR4 to the lipid raft was
      essential for the effects of heat on chemotaxis, as determined with an inhibitor
      of Rac1 activation, NSC23766. Application-wise, mild heat treatment significantly
      increased the percent chimerism as well as homing and engraftment of CD34(+) CB
      cells in sublethally irradiated non-obese diabetic severe combined
      immunodeficiency IL-2 receptor gamma chain d (NSG) mice. Mild heating may be a
      simple and inexpensive means to enhance engraftment following CB transplantation
      in patients.

PMID- 25753524
TI  - Identification of FOXM1 as a therapeutic target in B-cell lineage acute
      lymphoblastic leukaemia.
AB  - Despite recent advances in the cure rate of acute lymphoblastic leukaemia (ALL),
      the prognosis for patients with relapsed ALL remains poor. Here we identify FOXM1
      as a candidate responsible for an aggressive clinical course. We show that FOXM1
      levels peak at the pre-B-cell receptor checkpoint but are dispensable for normal
      B-cell development. Compared with normal B-cell populations, FOXM1 levels are 2-
      to 60-fold higher in ALL cells and are predictive of poor outcome in ALL
      patients. FOXM1 is negatively regulated by FOXO3A, supports cell survival, drug
      resistance, colony formation and proliferation in vitro, and promotes
      leukemogenesis in vivo. Two complementary approaches of pharmacological FOXM1
      inhibition-(i) FOXM1 transcriptional inactivation using the thiazole antibiotic
      thiostrepton and (ii) an FOXM1 inhibiting ARF-derived peptide-recapitulate the
      findings of genetic FOXM1 deletion. Taken together, our data identify FOXM1 as a
      novel therapeutic target, and demonstrate feasibility of FOXM1 inhibition in ALL.

PMID- 25753526
TI  - The effects of sports participation on the development of left ventricular mass
      in adolescent boys.
AB  - OBJECTIVES: To examine the contribution of body size, biological maturation, and
      nonelite sports participation to longitudinal changes of left ventricular mass
      (LVM) in healthy boys. METHODS: One hundred and ten boys (11.0-14.5 years at
      baseline) were assessed biannually for 2 years. Stature, body mass, and four
      skinfolds were measured. Lean body mass (LBM) was estimated. Biological
      maturation was assessed as years from age at peak height velocity (APHV). Sports
      participation was assessed by questionnaire. LVM was obtained from M-mode
      echocardiograms using two-dimensional images. To account for the repeated
      measures within individual nature of longitudinal data, multilevel random effects
      regression analyses were used in the analysis. RESULTS: LVM increased on average
      42 +/- 18 g from 11 to 15 years (P < 0.05) and 76 +/- 14 g from 3.5 years pre
      APHV to 1.5 years post-APHV (P < 0.05). The multilevel model with the best
      statistical fit (Model B) showed that changes of 1 cm in stature, 1 year post
      APHV, and 1 kg of LBM predicts 4.7, 0.5, and 1 g of LVM (P < 0.05), respectively.
      CONCLUSIONS: Among healthy, male adolescents aged 11-15 years individual
      differences in growth and biological maturation influence growth of LVM.
      Subcutaneous adiposity and sports participation were not associated with greater
      LVM.

PMID- 25753527
TI  - Protein correlates of molecular alterations in lung adenocarcinoma:
      Immunohistochemistry as a surrogate for molecular analysis.
AB  - Most clinically actionable alterations in lung adenocarcinomas are detected using
      molecular or cytogenetic techniques. However, many such alterations have a
      protein-level correlate that can be interrogated using immunohistochemistry. This
      review will summarize the therapeutic relevance of predictive biomarkers in lung
      adenocarcinoma including the oncogenes EGFR, MET, ALK, RET, and ROS1 and tumor
      suppressors PTEN and LKB1 with an emphasis on established and emerging protein
      immunohistochemistry reagents and their promise in clinical practice. 

PMID- 25753528
TI  - Outcome prediction for patients with renal cell carcinoma.
AB  - Outcome assessment for renal cell carcinoma is somewhat controversial. Despite
      numerous studies, a very limited variety of features have been recognized as
      having prognostic significance in clinical practice. In this review, tumor
      features considered to be of importance in outcome prediction for surgically
      treated patients with the 3 most commonly encountered morphotypes of renal cell
      carcinoma (clear cell, papillary, and chromophobe renal cell carcinoma) are
      evaluated. In particular, we have focused upon histologic subtype, sarcomatoid
      and rhabdoid differentiation, TNM staging, primary tumor size, tumor grade, and
      the presence of histologic coagulative tumor necrosis. We have also examined the
      importance of these prognostic features in a variety of postoperative or outcome
      prediction models developed by several institutions. 

PMID- 25753529
TI  - The evolving classification of renal cell neoplasia.
AB  - The classification of renal cell neoplasia is morphologically based; however,
      this has evolved over the last 35 years with the incorporation of genetic
      characteristics into the diagnostic features of some tumors. The 2013 Vancouver
      classification recognized 17 morphotypes of renal parenchymal malignancy and two
      benign tumors. This classification included the newly established entities
      tubulocystic renal cell carcinoma (RCC)), acquired cystic disease-associated RCC,
      clear cell (tubulo) papillary RCC, microphthalmia transcription factor family
      translocation RCC and hereditary leiomyomatosis RCC syndrome-associated RCC. In
      addition to these newly described forms of RCC there are a number of novel tumors
      that are currently recognized as emerging entities. These are likely to be
      incorporated into subsequent classifications and include thyroid-like follicular
      RCC, succinate dehydrogenase B mutation-associated RCC, ALK translocation RCC,
      tuberous sclerosis complex-associated RCC, and RCC with (angio) leiomyomatous
      stroma. 

PMID- 25753530
TI  - Cytologic mimics of non-Hodgkin lymphoma in the head and neck.
AB  - Non-lymphoid small round blue cell tumors of the head and neck are particularly
      difficult to diagnose when metastatic to a lymph node. The cytopathologist or
      surgical pathologist evaluating these lesions has to be aware of the various non
      hematopoetic neoplasms that present in the head and neck area that can mimic non
      Hodgkin lymphoma. Presented here are the various lesions commonly seen which
      needs to be entertained depending on where in the head and neck the lesion is
      located. More recently, a plethora of HPV related head and neck tumors has been
      described and these lesions add to the mix in this challenging milieu of cases. 

PMID- 25753531
TI  - Current treatment options in patients with mastocytosis: status in 2015 and
      future perspectives.
AB  - Mastocytosis is a term referring to a heterogeneous group of disorders
      characterized by abnormal mast cell (MC) accumulation in the skin and/or internal
      organs. In children, the disease involves mostly the skin (cutaneous
      mastocytosis; CM), whereas in adults, the disease is usually systemic (systemic
      mastocytosis; SM). Advanced SM variants with end-organ damage and reduced life
      expectancy have also been described, but are rare. Clinical signs and symptoms in
      SM result from excessive mediator release by MCs and, in aggressive forms, from
      organ failure related to MC infiltration. As a consequence, treatment of indolent
      SM aims primarily at the control of symptoms caused by MC mediator release. By
      contrast, in advanced SM, such as aggressive SM, MC leukemia, and MC sarcoma,
      intensive (chemo)therapy with or without allogeneic stem cell transplantation has
      to be considered. In addition, activating mutations in KIT (mostly KIT D816V in
      adults) are found in most patients with SM, so that targeted therapies aimed at
      blocking mutant KIT variants or/and downstream signaling pathways are currently
      being developed. Other targets, such as specific surface antigens expressed on
      neoplastic MCs, might be considered for the development of future therapies in
      advanced SM. 

PMID- 25753533
TI  - A dose-response meta-analysis of the impact of body mass index on stroke and all
      cause mortality in stroke patients: a paradox within a paradox.
AB  - The obesity paradox is often attributed to fat acting as a buffer to protect
      individuals in fragile metabolic states. If this was the case, one would predict
      that the reverse epidemiology would be apparent across all causes of mortality
      including that of the particular disease state. We performed a dose-response meta
      analysis to assess the impact of body mass index (BMI) on all-cause and stroke
      specific mortality among stroke patients. Data from relevant studies were
      identified by systematically searching PubMed, OVID and Scopus databases and were
      analysed using a random-effects dose-response model. Eight cohort studies on all
      cause mortality (with 20,807 deaths of 95,651 stroke patients) and nine studies
      of mortality exclusively because of stroke (with 8,087 deaths of 28,6270
      patients) were evaluated in the meta-analysis. Non-linear associations of BMI
      with all-cause mortality (P < 0.0001) and mortality by stroke (P = 0.05) were
      observed. Among overweight and obese stroke patients, the risk of all-cause
      mortality increased, while the risk of mortality by stroke declined, with an
      increase in BMI. Increasing BMI had opposite effects on all-cause mortality and
      stroke-specific mortality in stroke patients. Further investigations are needed
      to examine how mortality by stroke is influenced by a more accurate indicator of
      obesity than BMI. 

PMID- 25753532
TI  - Tuning IL-2 signaling by ADP-ribosylation of CD25.
AB  - Control of immunologic tolerance and homeostasis rely on Foxp3(+)CD4(+)CD25(+)
      regulatory T cells (Tregs) that constitutively express the high affinity receptor
      for Interleukin-2, CD25. Tregs proliferate in response to injections of IL-2/anti
      IL-2 antibody complexes or low doses of IL-2. However, little is known about
      endogenous mechanisms that regulate the sensitivity of CD25 to signaling by IL-2.
      Here we demonstrate that CD25 is ADP-ribosylated at Arg35 in the IL-2 binding
      site by ecto-ADP-ribosyltransferase ARTC2.2, a toxin-related GPI-anchored ecto
      enzyme. ADP-ribosylation inhibits binding of IL-2 by CD25, IL-2- induced
      phosphorylation of STAT5, and IL-2-dependent cell proliferation. Our study
      elucidates an as-yet-unrecognized mechanism to tune IL-2 signaling. This newly
      found mechanism might thwart Tregs at sites of inflammation and thereby permit a
      more potent response of activated effector T cells. 

PMID- 25753534
TI  - Molecular and Genetic Analyses of Collagen Type IV Mutant Mouse Models of
      Spontaneous Intracerebral Hemorrhage Identify Mechanisms for Stroke Prevention.
AB  - BACKGROUND: Collagen type IV alpha1 (COL4A1) and alpha2 (COL4A2) form
      heterotrimers critical for vascular basement membrane stability and function.
      Patients with COL4A1 or COL4A2 mutations suffer from diverse cerebrovascular
      diseases, including cerebral microbleeds, porencephaly, and fatal intracerebral
      hemorrhage (ICH). However, the pathogenic mechanisms remain unknown, and there is
      a lack of effective treatment. METHODS AND RESULTS: Using Col4a1 and Col4a2
      mutant mouse models, we investigated the genetic complexity and cellular
      mechanisms underlying the disease. We found that Col4a1 mutations cause abnormal
      vascular development, which triggers small-vessel disease, recurrent hemorrhagic
      strokes, and age-related macroangiopathy. We showed that allelic heterogeneity,
      genetic context, and environmental factors such as intense exercise or
      anticoagulant medication modulated disease severity and contributed to phenotypic
      heterogeneity. We found that intracellular accumulation of mutant collagen in
      vascular endothelial cells and pericytes was a key triggering factor of ICH.
      Finally, we showed that treatment of mutant mice with a US Food and Drug
      Administration-approved chemical chaperone resulted in a decreased collagen
      intracellular accumulation and a significant reduction in ICH severity.
      CONCLUSIONS: Our data are the first to show therapeutic prevention in vivo of ICH
      resulting from Col4a1 mutation and imply that a mechanism-based therapy promoting
      protein folding might also prevent ICH in patients with COL4A1 and COL4A2
      mutations.

PMID- 25753536
TI  - Mitophagy and mitochondrial dynamics in Saccharomyces cerevisiae.
AB  - Mitochondria fulfill central cellular functions including energy metabolism, iron
      sulfur biogenesis, and regulation of apoptosis and calcium homeostasis.
      Accumulation of dysfunctional mitochondria is observed in ageing and many human
      diseases such as cancer and various neurodegenerative disorders. Appropriate
      quality control of mitochondria is important for cell survival in most eukaryotic
      cells. One important pathway in this respect is mitophagy, a selective form of
      autophagy which removes excess and dysfunctional mitochondria. In the past
      decades a series of essential factors for mitophagy have been identified and
      characterized. However, little is known about the molecular mechanisms regulating
      mitophagy. The role of mitochondrial dynamics in mitophagy is controversially
      discussed. Here we will review recent advances in this context promoting our
      understanding on the molecular regulation of mitophagy in Saccharomyces
      cerevisiae and on the role of mitochondrial dynamics in mitochondrial quality
      control.

PMID- 25753535
TI  - Infective endocarditis after transcatheter aortic valve implantation: results
      from a large multicenter registry.
AB  - BACKGROUND: We aimed to determine the incidence, predictors, clinical
      characteristics, management, and outcomes of infective endocarditis (IE) after
      transcatheter aortic valve implantation (TAVI). METHODS AND RESULTS: This
      multicenter registry included 53 patients (mean age, 79+/-8 years; men, 57%) who
      suffered IE after TAVI of 7944 patients after a mean follow-up of 1.1+/-1.2 years
      (incidence, 0.67%, 0.50% within the first year after TAVI). Mean time from TAVI
      was 6 months (interquartile range, 1-14 months). Orotracheal intubation (hazard
      ratio, 3.87; 95% confidence interval, 1.55-9.64; P=0.004) and the self-expandable
      CoreValve system (hazard ratio, 3.12; 95% confidence interval, 1.37-7.14;
      P=0.007) were associated with IE (multivariate analysis including 3067 patients
      with individual data). The most frequent causal microorganisms were coagulase
      negative staphylococci (24%), followed by Staphylococcus aureus (21%) and
      enterococci (21%). Vegetations were present in 77% of patients (transcatheter
      valve leaflets, 39%; stent frame, 17%; mitral valve, 21%). At least 1
      complication of IE occurred in 87% of patients (heart failure in 68%). However,
      only 11% of patients underwent valve intervention (valve explantation and valve
      in-valve procedure in 4 and 2 patients, respectively). The mortality rate in
      hospital was 47.2% and increased to 66% at the 1-year follow-up. IE complications
      such as heart failure (P=0.037) and septic shock (P=0.002) were associated with
      increased in-hospital mortality. CONCLUSIONS: The incidence of IE at 1 year after
      TAVI was 0.50%, and the risk increased with the use of orotracheal intubation and
      a self-expandable valve system. Staphylococci and enterococci were the most
      common agents. Although most patients presented at least 1 complication of IE,
      valve intervention was performed in a minority of patients, and nearly half of
      the patients died during the hospitalization period.

PMID- 25753537
TI  - Mitochondrial autophagy: Origins, significance, and role of BNIP3 and NIX.
AB  - Mitochondrial autophagy (mitophagy) is a core cellular activity. In this review,
      we consider mitophagy and related cellular processes and discuss their
      significance for human disease. Strong parallels exist between mitophagy and
      xenophagy employed in host defense. These mechanisms converge on receptors in the
      innate immune system in clinically relevant scenarios. Mitophagy is part of a
      cellular quality control mechanism, which is implicated in degenerative disease,
      especially neurodegenerative disease. Furthermore, mitophagy is an aspect of
      cellular remodeling, which is employed during development. BNIP3 and NIX are
      related multi-functional outer mitochondrial membrane proteins. BNIP3 regulates
      mitophagy during hypoxia, whereas NIX is required for mitophagy during
      development of the erythroid lineage. Recent advances in the field of BNIP3- and
      NIX-mediated mitophagy are discussed.

PMID- 25753538
TI  - Erratum to: Lipid-modified azurin of Neisseria meningitidis is a copper protein
      localized on the outer membrane surface and not regulated by FNR.

PMID- 25753539
TI  - Rhodococcus agglutinans sp. nov., an actinobacterium isolated from a soil sample.
AB  - A Gram-positive, aerobic, non-motile and non-spore forming strain, designated CFH
      S0262(T), was isolated from a soil sample collected from Catba island in Halong
      Bay, Vietnam. A polyphasic approach was used to study the taxonomic position of
      this new isolate. Phylogenetic analyses based on 16S rRNA gene sequence showed
      that strain CFH S0262(T) belongs to the genus Rhodococcus and clustered with
      Rhodococcus soli DSD51W(T), Rhodococcus hoagii NBRC 103062(T), Rhodococcus
      defluvii Call(T) and Rhodococcus kunmingensis YIM 45607(T) (98.7, 98.5, 97.9 and
      97.6% similarities, respectively). Strain CFH S0262(T) could grow in the presence
      of NaCl (0-4%, optimum 0-3%), at pH 6.0-8.0 (optimum, pH 7.0) and at 10-40 
      degrees C (optimum, 28  degrees C). The predominant menaquinones of strain CFH
      S0262(T) were identified as MK-8 (H2) and MK-8 (H4). The major fatty acids
      (>=10%) were found to be C(16:0) and C(18:1)omega9c. The polar lipids detected
      were diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylinositol,
      phosphatidylinositol mannoside, a glycolipid and two unidentified phospholipids.
      The DNA G+C content was determined to be 71.4 mol%. Based on a comparative
      analysis of phenotypic and genotypic characteristics, in combination with low
      values of DNA-DNA hybridization between strain CFH S0262(T) and its closest
      neighbours, it is proposed that strain CFH S0262(T) represents a novel species of
      the genus Rhodococcus, for which the name Rhodococcus agglutinans sp. nov., is
      proposed, with the type strain CFH S0262(T) (=CCTCC AB2014297(T)=KCTC 39118(T)).

PMID- 25753540
TI  - Bifidobacterium commune sp. nov. isolated from the bumble bee gut.
AB  - Bifidobacteria were isolated from the gut of Bombus lapidarius, Bombus terrestris
      and Bombus hypnorum bumble bees by direct isolation on modified trypticase
      phytone yeast extract agar. The MALDI-TOF MS profiles of four isolates (LMG
      28292(T), R-53560, R-53124, LMG 28626) were found to be identical and did not
      cluster with the profiles of established Bifidobacterium species. Analysis of the
      16S rRNA gene sequence of strain LMG 28292(T) revealed that LMG 28292(T) is most
      closely related to the Bifidobacterium bohemicum type strain (96.8%), which was
      also isolated from bumble bee gut specimens. The hsp60 gene of strain LMG
      28292(T) shows 85.8% sequence similarity to that of the B. bohemicum type strain.
      The (GTG)5-PCR profiles and the hsp60 sequences of all four isolates were
      indistinguishable; however, three different phenotypes were observed among the
      four isolates by means of the API 50CHL microtest system. Based on the
      phylogenetic, genotypic and phenotypic data, we propose to classify the four
      isolates within the novel species Bifidobacterium commune sp. nov., with LMG
      28292(T) (= DSM 28792(T)) as the type strain.

PMID- 25753541
TI  - New-onset diabetes mellitus after shock wave lithotripsy for urinary stone: a
      systematic review and meta-analysis.
AB  - The purpose of the study was to evaluate the association between shock wave
      lithotripsy (SWL) for urinary stone and new-onset diabetes mellitus (DM). A
      comprehensive data collection was performed in the Pubmed database, Embase
      database, Chinese Biomedical database, Chinese National Knowledge Infrastructure
      database and VIP database. Difference in incidence of new-onset DM after SWL
      between cases and controls was evaluated by odds ratio (OR) with its 95%
      confidence interval (CI). And summary adjusted risk ratios (RRs) and 95% CIs were
      calculated to assess the strength of association between SWL and new-onset DM,
      and then subgroup analyses were conducted. Five studies were included in this
      meta-analysis. The incidence of new-onset DM after SWL is not higher than that in
      the population who do not receive SWL [OR = 1.59, 95% CI (0.92, 2.74), P = 0.10].
      And statistical association between SWL and new-onset DM could not be found
      significantly [RR = 1.33, 95% CI (0.83, 2.13), P = 0.24], either. However, body
      mass index (BMI) [RR = 1.09, 95% CI (1.04, 1.14), P < 0.001] and family history
      of DM (FHx DM) [RR = 0.35, 95% CI (0.15, 0.80), P = 0.013] were found
      significantly associated with the development of DM in subgroup analyses. Our
      data suggests that there is no association between SWL for urinary stone and new
      onset DM.

PMID- 25753542
TI  - Solitary fibrous tumor of the greater omentum.

PMID- 25753543
TI  - Mesenteric cavernous hemangioma: Imaging-pathologic correlation.

PMID- 25753544
TI  - Pulmonary aspergillosis.
AB  - Aspergillosis is a mycotic disease usually caused by Aspergillus fumigatus, a
      saprophytic and ubiquitous airborne fungus. Aspergillus-related lung diseases are
      traditionally classified into four different forms, whose occurrence depends on
      the immunologic status of the host and the existence of an underlying lung
      disease. Allergic broncho-pulmonary aspergillosis (ABPA) affects patients with
      asthma or cystic fibrosis. Saprophytic infection (aspergilloma) occurs in
      patients with abnormal airways (chronic obstructive pulmonary disease,
      bronchiectasis, cystic fibrosis) or chronic lung cavities. Chronic necrotizing
      aspergillosis (semi-invasive form) is described in patients with chronic lung
      pathology or mild immunodeficiency. Invasive aspergillosis (angio-invasive or
      broncho-invasive forms) occurs in severely immuno-compromised patients. Knowledge
      of the various radiological patterns for each form, as well as the corresponding
      associated immune disorders and/or underlying lung diseases, helps early
      recognition and accurate diagnosis. 

PMID- 25753545
TI  - Mucin-producing tumors of the ovary: MR imaging appearance.
AB  - Mucin-producing tumors of the ovary can be either primary epithelial mucin
      producing tumors or ovarian metastases from a remote adenocarcinoma usually
      originating from the gastrointestinal tract. The purpose of this pictorial review
      is to describe the main types of primary or secondary mucin-producing tumors of
      the ovary and to provide MR imaging diagnostic criteria in order to guide further
      therapy. 

PMID- 25753546
TI  - Elevational variation in adult body size and growth rate but not in metabolic
      rate in the tree weta Hemideina crassidens.
AB  - Populations of the same species inhabiting distinct localities experience
      different ecological and climatic pressures that might result in differentiation
      in traits, particularly those related to temperature. We compared metabolic rate
      (and its thermal sensitivity), growth rate, and body size among nine high- and
      low-elevation populations of the Wellington tree weta, Hemideina crassidens,
      distributed from 9 to 1171 m a.s.l across New Zealand. Our results did not
      indicate elevational compensation in metabolic rates (metabolic cold adaptation).
      Cold acclimation decreased metabolic rate compared to warm-acclimated individuals
      from both high- and low-elevation populations. However, we did find
      countergradient variation in growth rates, with individuals from high-elevation
      populations growing faster and to a larger final size than individuals from low
      elevation populations. Females grew faster to a larger size than males, although
      as adults their metabolic rates did not differ significantly. The combined
      physiological and morphological data suggest that high-elevation individuals grow
      quickly and achieve larger size while maintaining metabolic rates at levels not
      significantly different from low-elevation individuals. Thus, morphological
      differentiation among tree weta populations, in concert with genetic variation,
      might provide the material required for adaptation to changing conditions.

PMID- 25753547
TI  - Interventional Procedures for Chronic Pain in Children and Adolescents: A Review
      of the Current Evidence.
AB  - This review discusses the role of interventional procedures in the treatment of
      chronic pain in children and adolescents. Due to lack of scientific evidence,
      significant controversy surrounds the utility of invasive techniques for managing
      pediatric chronic pain states. Interventional procedures are a widely accepted
      modality for pain management in adults. The use of such techniques in children is
      supported only by case reports, case series, and very few randomized controlled
      studies. In addition, the potential for severe complications leaves open a debate
      on the safety of these invasive procedures, which must be confirmed by more
      extensive and accurate prospective studies.

PMID- 25753548
TI  - Direct observation of Ca(2+) -induced calmodulin conformational transitions in
      intact Xenopus laevis oocytes by (19) F NMR spectroscopy.
AB  - The Ca(2+) -mediated conformational transition of the protein calmodulin (CaM) is
      essential to a variety of signal transduction pathways. Whether the transition in
      living cells is similar to that observed in buffer is not known. Here, we report
      the direct observation by (19) F NMR spectroscopy of the transition of the Ca(2+)
      -free and -bound forms in Xenopus laevis oocytes at different Ca(2+) levels. We
      find that the Ca(2+) -bound CaM population increased greatly upon binding the
      target protein myosin light-chain kinase (MLCK) at the same Ca(2+) level.
      Paramagnetic NMR spectroscopy was also exploited for the first time to obtain
      long-range structural constraints in cells. Our study shows that (19) F NMR
      spectroscopy can be used to obtain long-range structural constraints in living
      eukaryotic cells and paves the way for quantification of protein binding
      constants. 

PMID- 25753549
TI  - A Battery Life beyond His "Expectancy".

PMID- 25753550
TI  - The gastro-intestinal tract as the major site of biological action of dietary
      melanoidins.
AB  - Emerging evidence from laboratory researches has highlighted the bioactivity of
      food melanoidins and melanoproteins. Whilst such studies have been carried out
      with different in vitro systems, information about melanoidins absorption and bio
      availability are scarce. However, they are generally considered as poorly
      absorbable and bio-available compounds. Therefore, we present a review in which
      the gastro-intestinal tract is hypothesized to be the main site of action of food
      melanoidins and melanoproteins biological activity. We described recent data
      supporting this hypothesis both in vitro model systems and in vivo. Importantly,
      we focused this review only on the effect of melanoidins and melanoproteins
      extracted from food. Most of the studies had been carried out using water-soluble
      carbohydrate-based melanoidins isolated from different food sources (beer, barley
      coffee, coffee). In bakery products, melanoidins are protein-based structure
      (melanoproteins) which are largely insoluble in water. Dietary melanoidins and
      melanoproteins have been demonstrated to exert in vitro antioxidant and metal
      chelating ability in the gastro-intestinal tract reducing the formation of lipid
      hydroperoxides and advanced lipid oxidation end products during the digestion of
      meat. The reduction in the formation of these pro-atherogenic compounds has been
      shown to be followed by a decrease in their absorption in human volunteers. Food
      melanoidins have also shown in vitro anti-caries and prebiotic activities. We
      conclude by underlining the possible role of food melanoidins in the prevention
      of gastro-intestinal tract cancers. We hope this review will stimulate further
      research on food melanoidins and their biological activities in the gastro
      intestinal tract.

PMID- 25753552
TI  - The effect of the systemic inflammatory response on plasma zinc and selenium
      adjusted for albumin.
AB  - BACKGROUND & AIM: The magnitude of systemic inflammatory response, as evidenced
      by C-reactive protein (CRP), is a major factor associated with lower zinc and
      selenium. They may also be influenced by their binding proteins, such as albumin.
      The aim of the present study was to examine the relationships between plasma
      zinc, selenium and the systemic inflammatory response in a large cohort of
      patients referred for nutritional screen and also to examine these relationships
      in patients with critical illness. METHODS: Patients referred for nutritional
      assessment of zinc (n = 743) and selenium (n = 833) and 114 patients with
      critical illness were examined. Intra-assay imprecision was <10% for these
      analytes. RESULTS: In the nutritional screen cohort, plasma zinc was
      significantly associated with CRP (rs = -0.404, p < 0.001) and albumin (rs =
      0.588, p < 0.001). For each CRP category (<=10, 11-80, >80 mg/l) the zinc/albumin
      ratio x100 was similar (31, 33 and 32 respectively, p = 0.029). Plasma selenium
      was significantly associated with CRP (rs = -0.489, p < 0.001) and albumin (rs =
      0.600, p < 0.001). With increasing CRP category (<=10, 11-80, >80 mg/l) the
      selenium/albumin ratio *100 was lower (2.3, 2.1 and 1.8 respectively, p < 0.001).
      Similar relationships were also observed in the cohort of patients with critical
      illness. CONCLUSION: Plasma zinc was associated with both CRP and albumin. The
      impact of the systemic inflammatory response could be largely adjusted by albumin
      concentrations. Plasma selenium was associated with both CRP and albumin. The
      impact of the systemic inflammatory response on plasma selenium concentrations
      could not be reasonably adjusted by albumin concentrations.

PMID- 25753551
TI  - Macronutrient intake and body composition changes during anti-tuberculosis
      therapy in adults.
AB  - BACKGROUND: Malnutrition is common in patients with active tuberculosis (TB), yet
      little information is available on serial dietary intake or body composition in
      TB disease. OBJECTIVE: To evaluate macronutrient intake and body composition in
      individuals with newly diagnosed TB over time. DESIGN: Adults with active
      pulmonary TB (n = 191; 23 with multidrug resistant TB (MDR-TB) and 36 culture
      negative household contacts (controls) enrolled in a clinical trial of high-dose
      cholecalciferol (vitamin D3) were studied. Macronutrient intake was determined at
      baseline, 8 and 16 weeks. Serial body composition was assessed by body mass index
      (BMI; kg/m(2)) and bioelectrical impedance analysis (BIA) to estimate fat mass
      and fat-free mass. Descriptive statistics, repeated measures ANOVA for changes
      over time and linear regression were used. RESULTS: At baseline, mean daily
      energy, protein, fat and carbohydrate (CHO) intakes were significantly higher,
      and body weight, BMI, fat-free mass and fat mass were significantly lower,
      between TB subjects and controls. These remained significant after adjusting for
      age, gender, employment status and smoking. In all TB subjects, baseline mean
      daily intakes of energy, fat and protein were adequate when compared to the US
      Dietary Reference Intakes and protein significantly increased over time (p <
      0.0001). Body weight, BMI, and fat and fat-free mass increased over time. MDR-TB
      patients exhibited lower body weight and fat-free mass over time, despite similar
      daily intake of kcal, protein, and fat. CONCLUSIONS: Macronutrient intake was
      higher in TB patients than controls, but TB-induced wasting was evident. As
      macronutrient intake of TB subjects increased over time, there was a parallel
      increase in BMI, while body composition proportions were maintained. However,
      individuals with MDR-TB demonstrated concomitantly decreased body weight and fat
      free mass over time versus drug-sensitive TB patients, despite increased
      macronutrient intake. Thus, MDR-TB appears to blunt anabolism to macronutrient
      intake, likely reflecting the catabolic effects of TB.

PMID- 25753553
TI  - Inter-observer reliability of the PASI in a clinical setting.
AB  - BACKGROUND: With the evolving emphasis on evidence-based practice, the use of
      reliable clinical scales forms an important foundation for clinical assessment.
      The psoriasis area and severity index (PASI) is the most widely used tool for the
      measurement of psoriasis severity; however, there has been some debate over the
      potential reproducibility of PASI scoring. OBJECTIVES: To determine the inter
      observer reliability of the PASI at a large tertiary hospital with a psoriasis
      treatment centre. METHODS: In total, 34 patients who were due for their 3-monthly
      follow up at a psoriasis treatment centre were independently evaluated by five
      clinical staff (observers) from the Department of Dermatology. Each observer
      independently determined the PASI score of each patient and the inter-observer
      reliability coefficient was determined by employing intra-class correlation
      coefficients (ICC). RESULTS: There was a significant degree of concordance among
      the PASI scoring of observers (ICC = 0.804; CI 95%: 0.706-0.883). CONCLUSIONS:
      Our cross-sectional study suggests that the PASI provides a reproducible method
      of assessing psoriasis severity among patients seen in a busy dermatology clinic
      at a large tertiary hospital.

PMID- 25753554
TI  - TGF-beta and SMADs mRNA Expression in Pulmonary Sarcoidosis.
AB  - Lung fibrosis is a complication of sarcoidosis, in which TGF-beta/Smad pathway
      may play an important role. We evaluated gene expression of TGF-beta1, SMAD2, 3
      and 7 in bronchoalveolar lavage (BAL) cells and peripheral blood (PB) lymphocytes
      of sarcoidosis patients (n=94) to better understand the mechanisms of sarcoid
      inflammation. The relative gene expression was analyzed by qPCR method. Selected
      clinical/radiological features and biochemical markers were taken into account in
      the analysis. We found that TGF-beta1 and SMAD3 expressions in PB lymphocytes
      were significantly higher in sarcoidosis patients. Up-regulation of SMAD7
      (inhibitory Smad) and down-regulation of SMAD3 in BAL cells in all subgroups were
      found. The expression of TGF-beta1 in PB lymphocytes was the highest in patients
      with lung parenchymal involvement and in the insidious onset phenotype. The
      expression of TGF-beta1 in BAL cells was higher in patients with abnormal
      spirometry (p=0.012), and TGF-beta1 and SMAD3 in patients with restrictive
      pattern (p=0.034 and 0.031, respectively). Several statistically significant
      negative correlations were found between the expression levels of SMAD2 and 3 in
      BAL cells and various LFT parameters. We conclude that TGF-beta/Smad pathway is
      involved in the pathogenesis of pulmonary sarcoidosis. These biomarkers
      (especially TGF-beta1, SMAD2 and 3) are of a negative prognostic value.

PMID- 25753555
TI  - Decreased FAM107A Expression in Patients with Non-small Cell Lung Cancer.
AB  - Lung cancer is the leading cause of cancer-related death in the world. Early
      detection, based on molecular markers, could decrease mortality from this
      disease. Tumor development is often associated with inactivation or loss of tumor
      suppressor genes (TSGs). The aim of the present study was to analyze the
      expression level of FAM107A gene, a TSG located in 3p21.1, in lung cancer tumors
      and in tumor adjacent normal lung samples. Promoter methylation status of FAM107A
      was evaluated as the potential mechanism of its epigenetic silencing. The
      relationship between gene mRNA expression and tumor staging, metastasis status,
      and non-small cell lung cancer (NSCLC) histopathological subtypes in 60 patients
      was analyzed. Total RNA was isolated from tissue samples and gene expression was
      assessed in qPCR assay. Gene promoter methylation status was evaluated in MSP
      reactions, using bisulfite converted DNA and two pairs of primers: methylated and
      unmethylated. We found that the expression of the gene was dramatically decreased
      in all NSCLC samples and was significantly lower than in tumor adjacent normal
      lung tissue. Promoter methylation of FAM107A gene was confirmed only in the
      minority of NSCLCs. The results highlight the importance of FAM107A in lung
      carcinogenesis, although indicate other than promoter hypermethylation mechanism
      of the gene decreased expression. 

PMID- 25753556
TI  - Clinical Significance of HMGB-1 and TGF-beta Level in Serum and BALF of Advanced
      Non-Small Cell Lung Cancer.
AB  - Lung cancer is associated with poor prognosis. The aim of this study was to
      evaluate the clinical usefulness of HMGB-1 (high-mobility group protein B1) and
      TGF-beta (transforming growth factor beta) in patients with advanced non-small
      cell lung cancer (NSCLC). We studied 45 patients with NSCLC prior to
      chemotherapy, 23 patients with Besnier-Boeck-Schaumann (BBS) disease
      (sarcoidosis), and 15 healthy volunteers. HMGB-1 and TGF-beta levels were
      measured in serum and BALF samples using ELISA method. A higher serum HMGB-1 and
      TGF-beta levels were in NSCLC patients compared with the other groups. TGF-beta
      concentration in BALF was significantly higher in NSCLC than in healthy controls
      (p=0.047) but lower than in BBS (p=0.016). Serum HMGB-1 in NSCLC correlated with
      age and gender while its level in BALF was associated with distant metastasis. A
      higher levels of HMGB-1 in the serum of NSCLC patients with progressive disease
      was linked with shorter overall survival and disease-free survival. We found a
      positive correlation between HMGB-1 and TGF-beta in BALF of IIIB NSCLC group and
      overall survival (p=0.04; p=0.003). Our findings confirmed that the measurement
      of HMGB-1 and TGF-beta levels in serum and BALF of patients with NSCLC prior to
      treatment may have clinical usefulness and predict poor prognosis.

PMID- 25753557
TI  - An Update on Measles in Pakistan: Pakistan's New Polio in the Making.

PMID- 25753558
TI  - Meta-analysis on the association between toothbrushing and head and neck cancer.
AB  - BACKGROUND: Epidemiological studies have focused on the association between
      toothbrushing and head and neck cancer (HNC). However, the question of whether
      toothbrushing is associated with decreased risk of HNC remains unanswered. Since
      there is currently no systematic review or meta-analysis available to provide
      quantitative findings on this important clinical question; we consequently
      performed this meta-analysis to investigate the association between toothbrushing
      and HNC risk. METHODS: We searched PubMed and Embase up to January 13 (updated on
      October 20), 2014 to identify observational studies that investigated the
      association between toothbrushing and HNC. After study section and data
      extraction, the meta-analysis was conducted using RevMan 5.2 software. RESULTS: A
      total of 18 case-control studies involving 7068 cases and 9990 controls were
      included. The meta-analysis showed that compared with highest toothbrushing
      frequency, lowest level was significantly increased risk of HNC 2.08 times (odds
      ratio=2.08, 95% confidence interval=1.65-2.62). This significant association
      remained consistent after adjusting for smoking status and alcohol consumption.
      No publication bias was detected. CONCLUSIONS: This meta-analysis found frequency
      of toothbrushing was significantly associated with HNC risk. Effective
      toothbrushing may be potentially important for the prevention of HNC and we
      suggest that the frequency be twice per day (morning and night).

PMID- 25753559
TI  - Adjuvant treatment for head and neck cancer in solid organ transplant recipients.

PMID- 25753560
TI  - The challenge of blocking a wider family members of EGFR against head and neck
      squamous cell carcinomas.
AB  - Head and neck squamous cell carcinoma (HNSCC) represent 95% of head and neck
      cancer with an incidence of over half a million people globally. The prognosis
      for patients with recurrent or metastatic HNSCC is generally poor with low 5-year
      survival rates despite treatment advances over the past few decades.
      Consequently, it is essential to search for new biomarkers and effective therapy
      options to optimize HNSCC treatment. Epidermal growth factor receptor (EGFR) is
      overexpressed in approximately 90% of tumours. EGFR has become one of most common
      targets for new therapies being investigated in HNSCC. In this way, multiple
      therapies targeting EGFR in HNSCC have been tested but response rates are still
      low especially in the recurrent or metastatic setting. This has been attributed
      to mechanisms of resistance to EGFR-targeted therapies. Afatinib, an oral small
      molecule ErbB Family Blocker that irreversibly binds to ErbB1 (EGFR), ErbB2
      (HER2) and ErbB4 (HER4), is being investigated in HNSCC treatment with
      encouraging phase II results and several ongoing phase III trials. Results of
      these trials will help to understand the place of afatinib in the HNSCC treatment
      armamentarium. 

PMID- 25753562
TI  - Medical pluralism among indigenous peoples in northeast India - implications for
      health policy.
AB  - OBJECTIVES: The government of India is promoting and increasing investment in the
      traditional medicine systems of Ayurveda, Yoga, Unani, Siddha and Homeopathy
      (AYUSH) in the northeast region of India. But there are few empirical data that
      support this policy decision. This study estimates the awareness and use of the
      different medical systems in rural Meghalaya, a state in north-east India with a
      predominantly ethnic tribal population. METHOD: We conducted a cross-sectional
      multistage random sample household survey across all districts of Meghalaya. To
      enable appropriate estimates for the whole of rural Meghalaya, the data were
      weighted to allow for the probability of selection of households at each stage of
      the sampling process. RESULTS: Both local tribal medicine and biomedicine were
      widely accepted and used, but the majority (68.7%, 95% CI: 51.9-81.7) had not
      heard of AYUSH and even fewer had used it. Tribal medicine was used (79.1%, 95%
      CI 66.3-88.0), thought to be effective (87.5%, 95% CI: 74.2-94.1) and given in a
      variety of disorders, including both minor and major diseases. In the 3 months
      prior to the survey, 46.2% (95% CI: 30.5-62.8) had used tribal medicine. Only
      10.5% (95% CI: 6.1-17.6) reported ever using any of the AYUSH systems.
      CONCLUSION: Our comparative estimates of the awareness and use of tribal
      medicine, different systems of AYUSH and of biomedicine among indigenous
      populations of India question the basis on which AYUSH is promoted in the
      northeast region of India and in the state of Meghalaya in particular.

PMID- 25753561
TI  - Solid-phase synthesis, characterization, and cellular activities of collagen
      model nanodiamond-peptide conjugates.
AB  - Nanodiamonds (NDs) have received considerable attention as potential drug
      delivery vehicles. NDs are small (~5 nm diameter), can be surface modified in a
      controllable fashion with a variety of functional groups, and have little
      observed toxicity in vitro and in vivo. However, most biomedical applications of
      NDs utilize surface adsorption of biomolecules, as opposed to covalent
      attachment. Covalent modification provides reliable and reproducible ND
      biomolecule ratios, and alleviates concerns over biomolecule desorption prior to
      delivery. The present study has outlined methods for the efficient solid-phase
      conjugation of ND to peptides and characterization of ND-peptide conjugates.
      Utilizing collagen-derived peptides, the ND was found to support or even enhance
      the cell adhesion and viability activities of the conjugated sequence. Thus, NDs
      can be incorporated into peptides and proteins in a selective manner, where the
      presence of the ND could potentially enhance the in vivo activities of the
      biomolecule it is attached to.

PMID- 25753563
TI  - Decline of Ves v 5-specific blocking capacity in wasp venom-allergic patients
      after stopping allergen immunotherapy.
AB  - While allergen-specific immunotherapy (AIT) is very efficient in hymenoptera
      venom (HV)-allergic patients, long-term outcome after finishing AIT is not well
      investigated, especially regarding mechanisms that are suggested to contribute to
      allergen-specific tolerance. Here, we analyse the Ves v 5-inhibitory activity of
      sera from wasp venom-allergic patients using the novel cell-free enzyme-linked
      immunosorbent facilitated antigen binding (ELIFAB) assay. Compared to pre-AIT,
      sera from patients undergoing AIT displayed an increased ability to inhibit Ves v
      5 binding by IgE antibodies. In contrast, this inhibitory activity was reduced in
      patients having finished AIT 5-12 years ago. Allergen-blocking capacity
      correlated with serum concentrations of Ves v 5-specific IgG4 which rose during
      AIT but almost reached pretreatment levels in patients who had stopped AIT more
      than 5 years ago. These data raise questions about how long allergen tolerance is
      maintained in AIT-treated HV-allergic patients and suggest that the ELIFAB assay
      might be an easy-to-use tool assessing long-term tolerance in patients treated
      with HV-AIT.

PMID- 25753564
TI  - Oligoclonal bands in hereditary diffuse leukencephalopathy with spheroids.

PMID- 25753566
TI  - Angiogenic biomarkers in pregnancy: defining maternal and fetal health.
AB  - We review diagnostic and predictive roles of the angiogenic proteins placental
      growth factor, soluble fms-like tyrosine kinase 1, and soluble endoglin in
      preeclampsia, and their association with future cardiovascular disease, diabetes,
      and breast cancer. Specific patterns of these proteins represent preeclamptic
      prediction markers and combined with maternal and clinical characteristics, the
      predictive values increase. Women experiencing preeclampsia have increased risks
      of developing cardiovascular diseases and diabetes, and a decreased risk of
      breast cancer. High placental growth factor concentrations have, in elderly
      patients, been shown to predict cardiovascular events. Diabetes is also a risk
      factor for future cardiovascular disease. Diabetic vascular complications are
      associated with increased soluble endoglin concentrations, and vascular
      endothelial growth factor concentrations are correlated to HbA1c and fasting
      glucose. Hence dysregulation in angiogenic proteins may link preeclampsia and
      cardiovascular diseases, targeting women who could in future benefit from
      prophylactic programs to possibly prevent, delay or reduce cardiovascular
      disease. 

PMID- 25753567
TI  - Ultrastructure damage of oviduct telocytes in rat model of acute salpingitis.
AB  - Acute salpingitis (AS) is an inflammatory disease which causes severe damage to a
      subset of classically described cells lining in oviduct wall and contributes to
      interstitial fibrosis and fertility problems. Telocytes (TCs), a newly discovered
      peculiar type of stromal cells, have been identified in many organs, including
      oviduct, with proposed multiple potential bio-functions. However, with recent
      increasing reports regarding TCs alterations in disease-affected tissues, there
      is still lack of evidence about TCs involvement in AS-affected oviduct tissues
      and potential pathophysiological roles. We presently identified normal TCs by
      their characteristic ultrastructural features and immunophenotype. However, in AS
      affected oviduct tissues, TCs displayed multiple ultrastructural damage both in
      cellular body and prolongations, with obvious loss of TCs and development of
      tissue fibrosis. Furthermore, TCs lose their interstitial 3-D network connected
      by homocellular or heterocellular junctions between TCs and adjacent cells. And
      especially, TCs connected to the activated immunocytes (mononuclear cells,
      eosinophils) and affected local immune state (repression or activation).
      Meanwhile, massive neutrophils infiltration and overproduced Inducible Nitric
      Oxide Synthase (iNOS), COX-2, suggested mechanism of inflammatory-induced TCs
      damage. Consequently, TCs damage might contribute to AS-induced structural and
      reproductive functional abnormalities of oviduct, probably via: (i) substances,
      energy and functional insufficiency, presumably, e.g. TC-specific genetic
      material profiles, ion channels, cytoskeletal elements, Tps dynamics, etc., (ii)
      impaired TCs-mediated multicellular signalling, such as homeostasis/angiogenesis,
      tissue repair/regeneration, neurotransmission, (iii) derangement of 3-D network
      and impaired mechanical support for TCs-mediated multicellular signals within the
      stromal compartment, consequently induced interstitial fibrosis, (iv) involvement
      in local inflammatory process/ immunoregulation and possibly immune-mediated
      early pregnancy failure. 

PMID- 25753569
TI  - Inflammation, coagulation, endothelial dysfunction and oxidative stress in
      prediabetes--Biomarkers as a possible tool for early disease detection for rural
      screening.
AB  - OBJECTIVES: This study aims to increase understanding of the connection between
      oxidative stress and inflammation in diabetes disease progression to provide a
      basis for investigating improved diagnostic possibilities, treatment and
      prevention of prediabetes. DESIGN AND METHODS: Differences in the level of
      biochemical markers of oxidative stress (erythrocyte GSH/GSSG and urinary 8
      isoprostane), inflammation (CRP, IL-6), endothelial dysfunction (plasma
      homocysteine, urinary 8-hydroxy-2-deoxy-guanosine) and coagulation/fibrinolysis
      (C5a, D-Dimer) were determined in prediabetes and control subjects. RESULTS:
      While no difference was found in the 8-isoprostane levels between the two groups,
      the erythrocyte GSH/GSSG ratio was significantly reduced in the prediabetes group
      compared to control, indicating increased oxidative stress in the prediabetic
      state. Both urinary 8-OHdG and surprisingly also plasma homocysteine were
      significantly elevated in the prediabetes group, indicating endothelial
      dysfunction. The inflammation markers were slightly elevated in the prediabetic
      subjects and the same trend was found for the coagulation/fibrinolysis markers
      C5a and D-Dimer. These results were however not significant. CONCLUSIONS: The
      small elevation of blood glucose levels in the prediabetic state may have a
      detectable influence on endothelial function as indicated by changes to 8-OHdG,
      indicating an increased DNA-damage and homocysteine release from endothelial
      cells. Increased oxidative stress as indicated by the reduced GSH/GSSG ratio is
      likely to be the link between the moderate hyperglycaemia in prediabetes and
      pathological changes in endothelial function, which in the long-term may promote
      atherogenesis and result in the development of cardiovascular disease. Early
      detection of prediabetes is essential to avoid diabetes development and the
      associated complications like cardiovascular disease. The GSH/GSSG ratio and
      biomarkers like urinary 8-OHdG and plasma homocysteine offer a possible tool for
      the assessment of prediabetes in prevention screenings.

PMID- 25753568
TI  - Metabolic study of Angelica dahurica extracts using a reusable liver microsomal
      nanobioreactor by liquid chromatography-mass spectrometry.
AB  - Highly active and recoverable nanobioreactors prepared by immobilizing rat liver
      microsomes on magnetic nanoparticles (LMMNPs) were utilized in metabolic study of
      Angelica dahurica extracts. Five metabolites were detected in the incubation
      solution of the extracts and LMMNPs, which were identified by means of HPLC-MS as
      trans-imperatorin hydroxylate (M1), cis-imperatorin hydroxylate (M2), imperatorin
      epoxide (M3), trans-isoimperatorin hydroxylate (M1') and cis-isoimperatorin
      hydroxylate (speculated M2'). Compared with the metabolisms of imperatorin and
      isoimperatorin, it was found that the five metabolites were all transformed from
      these two major compounds present in the plant. Since no study on isoimperatorin
      metabolism by liver microsomal enzyme system has been reported so far, its
      metabolites (M1' and M3') were isolated by preparative HPLC for structure
      elucidation by (1) H-NMR and MS(2) analysis. M3' was identified as isoimperatorin
      epoxide, which is a new compound as far as its chemical structure is concerned.
      However, interestingly, M3' was not detected in the metabolism of the whole plant
      extract. In addition, a study with known chemical inhibitors on individual
      isozymes of the microsomal enzyme family revealed that CYP1A2 is involved in
      metabolisms of both isoimperatorin and imperatorin, and CYP3A4 only in that of
      isoimperatorin.

PMID- 25753570
TI  - Association of angiopoietin-1, angiopoietin-2 and caspase-5 polymorphisms with
      psoriasis vulgaris.
AB  - BACKGROUND: Psoriasis involves a multifaceted interplay of keratinocytes, blood
      vessels, immune system mediators and expressed genes. AIM: To determine whether
      genetic polymorphisms in the angiopoietin-1 (ANGPT1), angiopoietin-2 (ANGPT2) and
      caspase-5 (CASP5) genes are associated with an increased risk of developing
      psoriasis vulgaris (PV) in a Han population in northeastern China. METHODS: We
      analysed single nucleotide polymorphisms of ANGPT1 (rs2507800, rs1954727 and
      rs1010824), ANGPT2 (rs3739390, rs2442598 and rs1868554) and caspase-5 (rs507879,
      rs518604 and rs523104) in 343 patients with PV and 347 healthy controls (HCs) by
      the SNaPshot method, and evaluated the risk for psoriasis conferred by the
      individual polymorphisms and haplotypes. RESULTS: The rs2442598 polymorphism of
      ANGPT2 was significantly associated with PV. The CT+TT genotype was present at an
      increased frequency in patients with PV (adjusted OR = 1.45, 95% CI 1.04-2.03, P
      = 0.03). However, the distribution of the other genotypes (rs2507800, rs1954727
      and rs1010824 of ANGPT1; rs3739390 and rs1868554 of ANGPT2; and rs507879,
      rs518604 and rs523104 of caspase-5) was not significantly different between
      patients with PV and the HCs. Furthermore, none of the genes in the haplotype
      based analysis showed any association with psoriasis risk. CONCLUSIONS: Our data
      suggest that ANGPT2 variants may be involved in PV risk in a Han population in
      northeastern China.

PMID- 25753571
TI  - CD19 chimeric antigen receptor T cell therapy for haematological malignancies.
AB  - T cells can be redirected to recognize tumour antigens by genetic modification to
      express a chimeric antigen receptor (CAR). These consist of antibody-derived
      antigen-binding regions linked to T cell signalling elements. CD19 is an ideal
      target because it is expressed on most B cell malignancies as well as normal B
      cells but not on other cell types, restricting any 'on target, off tumour'
      toxicity to B cell depletion. Recent clinical studies involving CD19 CAR-directed
      T cells have shown unprecedented responses in a range of B cell malignancies,
      even in patients with chemorefractory relapse. Durable responses have been
      achieved, although the persistence of modified T cells may be limited. This
      therapy is not without toxicity, however. Cytokine release syndrome and
      neurotoxicity appear to be frequent but are treatable and reversible. CAR T cell
      therapy holds the promise of a tailored cellular therapy, which can form memory
      and be adapted to the tumour microenvironment. This review will provide a
      perspective on the currently available data, as well as on future developments in
      the field.

PMID- 25753572
TI  - Hormone therapy and risk of venous thromboembolism among postmenopausal women in
      Taiwan - a 10-year nationwide population-based study.
AB  - BACKGROUND: The incidence of venous thromboembolism (VTE) in Asians is lower than
      in Caucasians, but the risk of VTE associated with hormone therapy (HT) in
      Taiwanese postmenopausal women has not been determined. METHODS AND RESULTS: From
      Taiwan's National Health Insurance Research Database, we established matched
      cohorts (HT users and nonusers) of postmenopausal women aged >=50 years between 1
      January 1998 and 31 December 2008. We calculated the 2-year incidence of VTE in
      HT users and nonusers. HT users and nonusers were matched 1:1 based on propensity
      score matching. Cox regression hazard model was used to identify risk factors of
      VTE. We initially identified 499,594 HT users and 424,963 nonusers. There were
      higher percentages of cancer and cardiovascular events among the HT nonusers.
      After matching, the VTE incidence was 4.4 vs. 2.6 per 10,000 patient-years
      (adjusted hazard ratio 1.796, 95% confidence interval 1.272-2.537) in HT users
      and nonusers, respectively. The Cox regression hazard model showed that HT use,
      older age, malignancy, heart failure, and recent major surgery were independent
      risk factors for VTE. CONCLUSIONS: Although the incidence of VTE was very low
      among this cohort of Taiwanese postmenopausal women, oral HT was still associated
      with an increased risk of VTE. Therefore, physicians should be aware of other
      potential VTE risk factors when prescribing oral HT to postmenopausal women.

PMID- 25753573
TI  - How can we predict reduced fractional flow reserve using coronary lesion
      characteristics?

PMID- 25753574
TI  - Hydroclimatic changes and drivers in the Sava River Catchment and comparison with
      Swedish catchments.
AB  - In this study, we investigate long-term hydroclimatic changes and their possible
      relation to regional changes in climate, land-use and water-use over the
      twentieth century in the transboundary Sava River Catchment (SRC) in South
      Eastern Europe. In a hydropower dominated part of the SRC, unlike in an
      unregulated part, we find increase in average annual evapotranspiration and
      decrease in temporal runoff variability, which are not readily explainable by
      observed concurrent climate change in temperature and precipitation and may be
      more related to landscape-internal change drivers. Among the latter investigated
      here, results indicate hydropower developments as most closely related to the
      found hydroclimatic shifts, consistent with previous such indications in studies
      of Swedish hydropower catchments. Overall, the present results have
      quantitatively framed the recent history and present state of hydroclimate in the
      SRC, of relevance for water resources in several countries and for a majority of
      their populations. This provides a useful basis for further assessment of
      possible future hydroclimatic changes, under different scenarios of climate
      change and land/water-use developments in the region. 

PMID- 25753575
TI  - Current concepts for the biological basis of dental implants: foreign body
      equilibrium and osseointegration dynamics.
AB  - To understand the biological basis of osseointegration, one has to understand the
      2 main sides of the implant-host interaction: tissue and biomaterial
      characteristics. This article addresses osseous tissue characteristics, and the
      potential role of soft tissues in the osseointegration of dental implants.
      Successful integration is driven by an inflammatory process. Protein adsorption
      is key for tissue integration with biomaterials. Osseointegration dynamics relate
      to the in vivo lifetime of the implant. Understanding this biology is important;
      it opens the door to putting aside heuristic methods and replaces them by methods
      that produce solutions to achieve a specific biological goal.

PMID- 25753576
TI  - White Matter Hyperintensities and Mild Cognitive Impairment in Parkinson's
      Disease.
AB  - OBJECTIVES: The clinical implications of white matter hyperintensities (WMH) in
      non-demented Parkinson's disease (PD) have not been thoroughly examined. To
      address this, we investigated the spatial distribution of WMH and their regional
      predilection in non-demented patients with mild PD. METHODS: Cognitive
      assessments classified the sample into patients with mild cognitive impairment
      (PD-MCI, n = 25) and patients with no cognitive impairment (PD-NCI, n = 65) based
      on the recent formal Movement Disorder Task Force diagnostic criteria. The mean
      age was 65.1 +/- 7.7 years, disease duration was 5.3 +/- 3.9 years, and Hoehn and
      Yahr stage was 1.9 +/- .4. WMHs were outlined on T2-weighted imaging using a semi
      automated technique. The spatial distribution of WMHs were compared between PD
      MCI and PD-NCI using voxel-wise lesion probability maps (LPM). General linear
      models examined the associations between spatially specific WMHs and cognitive
      domains. RESULTS: LPM analyses showed significant differences in the spatial
      distribution of WMH in PD-MCI compared to PD-NCI in widespread regions of the
      brain (P < .05). PD-MCI demonstrated significantly greater total and
      periventricular WMHs compared to PD-NCI (P <= .02). Spatial distribution of WMHs
      was also significantly associated with global cognition, performance on the
      Frontal Assessment Battery and Fruit Fluency (P < .05). CONCLUSIONS: Voxel-wise
      LPM analysis revealed differences in the spatial distribution of WMH between PD
      MCI and PD-NCI patients, particularly in the periventricular regions. A more
      widespread extent of WMH might be indicative of cognitive deterioration. Our
      findings warrant further longitudinal investigation into the importance of WMH
      spatial distribution as a predictor for conversion from PD to PD with dementia.

PMID- 25753577
TI  - Preschool language variation, growth, and predictors in children on the autism
      spectrum.
AB  - BACKGROUND: There is wide variation in language abilities among young children
      with autism spectrum disorders (ASD), with some toddlers developing age
      appropriate language while others remain minimally verbal after age 5.
      Conflicting findings exist regarding predictors of language outcomes in ASD and
      various methodological issues limit the conclusions that can be drawn about
      factors associated with positive language growth that could provide insights into
      more effective intervention approaches for increasing communication skills.
      METHODS: Language development was investigated in 129 children with ASD
      participating in four assessments from mean age 21/2 years (Visit 1) through 51/2
      years (Visit 4). Language ability was measured by a clinician-administered test
      of comprehension and production. Hierarchical linear modeling was used to
      identify predictors of language ability. Stability of language status was
      examined in subgroups of Preverbal versus Verbal children identified at Visit 1.
      Discriminant function analysis was used to classify another subset of cases
      according to Low Language (minimally verbal) versus High Language outcome at
      Visit 4. RESULTS: ASD severity was a significant predictor of growth in both
      language comprehension and production during the preschool period, while
      cognition predicted growth in production. For the highest and lowest language
      performers at Visit 4, cognition, maternal education, and response to joint
      attention correctly classified over 80% of total cases. The vast majority of
      children who were preverbal at 21/2 years attained some level of verbal skills by
      51/2 years. CONCLUSIONS: Findings indicate that it is possible, by 21/2 years, to
      predict language growth for children with ASD across the preschool years and
      identify factors that discriminate between children who remain minimally verbal
      at 51/2 years from those with high language proficiency. Results suggest that
      early intervention focused on reducing core ASD symptoms may also be important
      for facilitating language development in young children with ASD.

PMID- 25753578
TI  - Novel genetic variants in differentiated thyroid cancer and assessment of the
      cumulative risk.
AB  - A genome-wide association study (GWAS) performed on a high-incidence Italian
      population followed by replications on low-incidence cohorts suggested a strong
      association of differentiated thyroid cancer (DTC) with single nucleotide
      polymorphisms (SNPs) at 9q22.33, 2q35, 20q11.22-q12 and 14q24.3. Moreover, six
      additional susceptibility loci were associated with the disease only among
      Italians. The present study had two aims, first to identify loci involved in DTC
      risk and then to assess the cumulative effect of the SNPs identified so far in
      the Italian population. The combined analysis of the previous GWAS and the
      present Italian study provided evidence of association with rs7935113 (GALNTL4,
      OR = 1.36, 95%CI 1.20-1.53, p-value = 7.41 * 10(-7)) and rs1203952 (FOXA2, OR =
      1.29, 95%CI 1.16-1.44, p-value = 4.42 * 10(-6)). Experimental ENCODE and eQTL
      data suggested that both SNPs may influence the closest genes expression through
      a differential recruitment of transcription factors. The assessment of the
      cumulative risk of eleven SNPs showed that DTC risk increases with an increasing
      number of risk alleles (p-trend = 3.13 * 10(-47)). Nonetheless, only a small
      fraction (about 4% on the disease liability scale) of DTC is explained by these
      SNPs. These data are consistent with a polygenic model of DTC predisposition and
      highlight the importance of association studies in the discovery of the disease
      hereditability. 

PMID- 25753579
TI  - Lin28b promotes fetal B lymphopoiesis through the transcription factor Arid3a.
AB  - Mouse B cell precursors from fetal liver and adult bone marrow (BM) generate
      distinctive B cell progeny when transplanted into immunodeficient recipients,
      supporting a two-pathway model for B lymphopoiesis, fetal "B-1" and adult "B-2."
      Recently, Lin28b was shown to be important for the switch between fetal and adult
      pathways; however, neither the mechanism of Lin28b action nor the importance of B
      cell antigen receptor (BCR) signaling in this process was addressed. Here, we
      report key advances in our understanding of the regulation of B-1/B-2
      development. First, modulation of Let-7 in fetal pro-B cells is sufficient to
      alter fetal B-1 development to produce B cells resembling the progeny of adult B
      2 development. Second, intact BCR signaling is required for the generation of B1a
      B cells from Lin28b-transduced BM progenitors, supporting a requirement for
      ligand-dependent selection, as is the case for normal B1a B cells. Third, the VH
      repertoire of Lin28b-induced BM B1a B cells differs from that of normal B1a,
      suggesting persisting differences from fetal progenitors. Finally, we identify
      the Arid3a transcription factor as a key target of Let-7, whose ectopic
      expression is sufficient to induce B-1 development in adult pro-B cells and whose
      silencing by knockdown blocks B-1 development in fetal pro-B cells. 

PMID- 25753581
TI  - The effectiveness of risk communication regarding drug safety information: a
      nationwide survey by the Japanese public health insurance claims data.
AB  - WHAT IS KNOWN AND OBJECTIVE: We evaluated the effectiveness of warning letters
      published by the pharmaceutical regulatory agency in Japan on communication of
      drug safety and risk by quantitative analysis of the national health insurance
      claims database (NHICD). We then explored what factors may have affected risk
      communication. METHODS: We measured the implementation rate of the hepatitis
      virus-monitoring test among methotrexate (MTX)-treated patients; a warning letter
      had been issued regarding the use of MTX, as it apparently activates the
      hepatitis virus. Data from the NHICD, which include 99.3% of Japanese residents,
      were used. A total of 4,933,481 patients with rheumatoid arthritis (RA) (January
      June, 2010) were the focus of this study. RESULTS: The implementation rate of the
      hepatitis virus-monitoring test increased from 1.4% before to 1.8% after the
      warning letter announcement. Logistic regression analysis suggested that the
      installation of a drug information management room is one of the important
      factors affecting risk communication. Further analysis revealed that the
      hepatitis virus monitoring rates in hospitals without drug information management
      rooms increased from 2.3% to 4.1% due to the issue of the warning letter. WHAT IS
      NEW AND CONCLUSION: The warning letter from the regulatory agency plays an
      important role in risk communication in hospitals without drug information
      management rooms.

PMID- 25753580
TI  - The interaction of anticancer therapies with tumor-associated macrophages.
AB  - Macrophages are essential components of the inflammatory microenvironment of
      tumors. Conventional treatment modalities (chemotherapy and radiotherapy),
      targeted drugs, antiangiogenic agents, and immunotherapy, including checkpoint
      blockade, all profoundly influence or depend on the function of tumor-associated
      macrophages (TAMs). Chemotherapy and radiotherapy can have dual influences on
      TAMs in that a misdirected macrophage-orchestrated tissue repair response can
      result in chemoresistance, but in other circumstances, TAMs are essential for
      effective therapy. A better understanding of the interaction of anticancer
      therapies with innate immunity, and TAMs in particular, may pave the way to
      better patient selection and innovative combinations of conventional approaches
      with immunotherapy. 

PMID- 25753582
TI  - Presence of bile acids in human follicular fluid and their relation with embryo
      development in modified natural cycle IVF.
AB  - STUDY QUESTION: Are bile acids (BA) and their respective subspecies present in
      human follicular fluid (FF) and do they relate to embryo quality in modified
      natural cycle IVF (MNC-IVF)? SUMMARY ANSWER: BA concentrations are 2-fold higher
      in follicular fluid than in serum and ursodeoxycholic acid (UDCA) derivatives
      were associated with development of top quality embryos on Day 3 after
      fertilization. WHAT IS KNOWN ALREADY: Granulosa cells are capable of synthesizing
      BA, but a potential correlation with oocyte and embryo quality as well as
      information on the presence and role of BA subspecies in follicular fluid have
      yet to be investigated. STUDY DESIGN, SIZE, DURATION: Between January 2001 and
      June 2004, follicular fluid and serum samples were collected from 303 patients
      treated in a single academic centre that was involved in a multicentre cohort
      study on the effectiveness of MNC-IVF. PARTICIPANTS/MATERIALS, SETTING, METHODS:
      Material from patients who underwent a first cycle of MNC-IVF was used. Serum was
      not stored from all patients, and the available material comprised 156 follicular
      fluid and 116 matching serum samples. Total BA and BA subspecies were measured in
      follicular fluid and in matching serum by enzymatic fluorimetric assay and liquid
      chromatography-mass spectrometry, respectively. The association of BA in
      follicular fluid with oocyte and embryo quality parameters, such as fertilization
      rate and cell number, presence of multinucleated blastomeres and percentage of
      fragmentation on Day 3, was analysed. MAIN RESULTS AND THE ROLE OF CHANCE:
      Embryos with eight cells on Day 3 after oocyte retrieval were more likely to
      originate from follicles with a higher level of UDCA derivatives than those with
      fewer than eight cells (P < 0.05). Furthermore, follicular fluid levels of
      chenodeoxycholic derivatives were higher and deoxycholic derivatives were lower
      in the group of embryos with fragmentation compared with those without (each P <
      0.05). Levels of total BA were 2-fold higher in follicular fluid compared with
      serum (P < 0.001), but had no predictive value for oocyte and embryo quality.
      LIMITATIONS, REASONS FOR CAUTION: Only samples originating from first cycle MNC
      IVF were used, which resulted in 14 samples only from women with an ongoing
      pregnancy, therefore further prospective studies are required to confirm the
      association of UDCA with IVF pregnancy outcomes. The inter-cycle variability of
      BA levels in follicular fluid within individuals has yet to be investigated. We
      checked for macroscopic signs of contamination of follicular fluid by blood but
      the possibility that small traces of blood were present within the follicular
      fluid remains. Finally, although BA are considered stable when stored at -20
      degrees C, there was a time lag of 10 years between the collection and analysis
      of follicular fluid and serum samples. WIDER IMPLICATIONS OF THE FINDINGS: The
      favourable relation between UDCA derivatives in follicular fluid and good embryo
      development and quality deserves further prospective research, with live birth
      rates as the end-point. STUDY FUNDING/COMPETING INTERESTS: This work was
      supported by a grant from the Netherlands Organisation for Scientific Research
      (VIDI Grant 917-56-358 to U.J.F.T.). No competing interests are reported.

PMID- 25753583
TI  - Aberrant DNA methylation patterns of spermatozoa in men with unexplained
      infertility.
AB  - STUDY QUESTION: Are there DNA methylation alterations in sperm that could explain
      the reduced biological fertility of male partners from couples with unexplained
      infertility? SUMMARY ANSWER: DNA methylation patterns, not only at specific loci
      but also at Alu Yb8 repetitive sequences, are altered in infertile individuals
      compared with fertile controls. WHAT IS KNOWN ALREADY: Aberrant DNA methylation
      of sperm has been associated with human male infertility in patients
      demonstrating either deficiencies in the process of spermatogenesis or low semen
      quality. STUDY DESIGN, SIZE, DURATION: Case and control prospective study. This
      study compares 46 sperm samples obtained from 17 normospermic fertile men and 29
      normospermic infertile patients. PARTICIPANTS/MATERIALS, SETTING, METHODS:
      Illumina Infinium HD Human Methylation 450K arrays were used to identify genomic
      regions showing differences in sperm DNA methylation patterns between five
      fertile and seven infertile individuals. Additionally, global DNA methylation of
      sperm was measured using the Methylamp Global DNA Methylation Quantification
      Ultra kit (Epigentek) in 14 samples, and DNA methylation at several repetitive
      sequences (LINE-1, Alu Yb8, NBL2, D4Z4) measured by bisulfite pyrosequencing in
      44 sperm samples. A sperm-specific DNA methylation pattern was obtained by
      comparing the sperm methylomes with the DNA methylomes of differentiated somatic
      cells using data obtained from methylation arrays (Illumina 450 K) of blood,
      neural and glial cells deposited in public databases. MAIN RESULTS AND THE ROLE
      OF CHANCE: In this study we conduct, for the first time, a genome-wide study to
      identify alterations of sperm DNA methylation in individuals with unexplained
      infertility that may account for the differences in their biological fertility
      compared with fertile individuals. We have identified 2752 CpGs showing aberrant
      DNA methylation patterns, and more importantly, these differentially methylated
      CpGs were significantly associated with CpG sites which are specifically
      methylated in sperm when compared with somatic cells. We also found statistically
      significant (P < 0.001) associations between DNA hypomethylation and regions
      corresponding to those which, in somatic cells, are enriched in the repressive
      histone mark H3K9me3, and between DNA hypermethylation and regions enriched in
      H3K4me1 and CTCF, suggesting that the relationship between chromatin context and
      aberrant DNA methylation of sperm in infertile men could be locus-dependent.
      Finally, we also show that DNA methylation patterns, not only at specific loci
      but also at several repetitive sequences (LINE-1, Alu Yb8, NBL2, D4Z4), were
      lower in sperm than in somatic cells. Interestingly, sperm samples at Alu Yb8
      repetitive sequences of infertile patients showed significantly lower DNA
      methylation levels than controls. LIMITATIONS, REASONS FOR CAUTION: Our results
      are descriptive and further studies would be needed to elucidate the functional
      effects of aberrant DNA methylation on male fertility. WIDER IMPLICATIONS OF THE
      FINDINGS: Overall, our data suggest that aberrant sperm DNA methylation might
      contribute to fertility impairment in couples with unexplained infertility and
      they provide a promising basis for future research. STUDY FUNDING/COMPETING
      INTERESTS: This work has been financially supported by Fundacion Cientifica de la
      AECC (to R.G.U.); IUOPA (to G.F.B.); FICYT (to E.G.T.); the Spanish National
      Research Council (CSIC; 200820I172 to M.F.F.); Fundacion Ramon Areces (to M.F.F);
      the Plan Nacional de I+D+I 2008-2011/2013-2016/FEDER (PI11/01728 to AF.F.,
      PI12/01080 to M.F.F. and PI12/00361 to S.L.); the PN de I+D+I 2008-20011 and the
      Generalitat de Catalunya (2009SGR01490). A.F.F. is sponsored by ISCIII
      Subdireccion General de Evaluacion y Fomento de la Investigacion (CP11/00131).
      S.L. is sponsored by the Researchers Stabilization Program from the Spanish
      National Health System (CES09/020). The IUOPA is supported by the Obra Social
      Cajastur, Spain.

PMID- 25753584
TI  - Introduction of periodic boundary conditions into UNRES force field.
AB  - In this article, implementation of periodic boundary conditions (PBC) into
      physics-based coarse-grained UNited RESidue (UNRES) force field is presented,
      which replaces droplet-like restraints previously used. Droplet-like restraints
      are necessary to keep multichain systems together and prevent them from
      dissolving to infinitely low concentration. As an alternative for droplet-like
      restrains cuboid PBCs with imaging of the molecules were introduced. Owing to
      this modification, artificial forces which arose from restraints keeping a
      droplet together were eliminated what leads to more realistic trajectories. Due
      to computational reasons cutoff and smoothing functions were introduced on the
      long range interactions. The UNRES force field with PBC was tested by performing
      microcanonical simulations. Moreover, to asses the behavior of the thermostat in
      PBCs Langevin and Berendsen thermostats were studied. The influence of PBCs on
      association pattern was compared with droplet-like restraints on the
      betabetaalpha hetero tetramer 1 protein system.

PMID- 25753585
TI  - Apoptotic Effect of Galbanic Acid via Activation of Caspases and Inhibition of
      Mcl-1 in H460 Non-Small Lung Carcinoma Cells.
AB  - Galbanic acid (GBA), a major compound of Ferula assafoetida, was known to have
      cytotoxic, anti-angiogenic and apoptotic effects in prostate cancer and murine
      Lewis lung cancer cells; the underling apoptotic mechanism of GBA still remains
      unclear so far. Thus, in the present study, the apoptotic mechanism of GBA was
      investigated mainly in H460 non-small cell lung carcinoma (NSCLC) cells because
      H460 cells were most susceptible to GBA than A549, PC-9 and HCC827 NSCLC cells.
      Galbanic acid showed cytotoxicity in wild EGFR type H460 and A549 cells better
      than other mutant type PC-9 and HCC827 NSCLC cells. Also, GBA significantly
      increased the number of Terminal deoxynucleotidyl transferase dUTP nick end
      labeling (TUNEL) positive cells and sub G1 population in H460 cells. Western
      blotting revealed that GBA cleaved poly (ADP-ribose) polymerase (PARP), activated
      Bax and caspase 9, attenuated the expression of Bcl-2, Bcl-x(L), and Myeloid cell
      leukemia 1 (Mcl-1) in H460 cells. However, interestingly, overexpression of Mcl-1
      blocked the ability of GBA to exert cytotoxicity, activate caspase9 and Bax,
      cleave PARP, and increase sub G1 accumulation in H460 cells. Overall, these
      findings suggest that GBA induces apoptosis in H460 cells via caspase activation
      and Mcl-1 inhibition in H460 cells as a potent anticancer agent for NSCLC
      treatment.

PMID- 25753586
TI  - Thinking outside the "bug": a unique assay to measure intracellular drug
      penetration in gram-negative bacteria.
AB  - Significant challenges are present in antibiotic drug discovery and development.
      One of these is the number of efficient approaches Gram-negative bacteria have
      developed to avoid intracellular accumulation of drugs and other cell-toxic
      species. In order to better understand these processes and correlate in vitro
      enzyme inhibition to whole cell activity, a better assay to evaluate a key
      factor, intracellular accumulation of the drug, is urgently needed. Here, we
      describe a unique liquid chromatography (LC)-mass spectrometry (MS) approach to
      measure the amount of cellular uptake of antibiotics by Gram-negative bacteria.
      This method, which measures the change of extracellular drug concentration, was
      evaluated by comparing the relative uptake of linezolid by Escherichia coli wild
      type versus an efflux pump deficient strain. A higher dosage of the drug showed a
      higher accumulation in these bacteria in a dosing range of 5-50 ng/mL. The
      Escherichia coli efflux pump deficient strain had a higher accumulation of the
      drug than the wild-type strain as predicted. The approach was further validated
      by determining the relative meropenem uptake by Pseudomonas aeruginosa wild-type
      versus a mutant strain lacking multiple porins. These studies show great promise
      of being applied within antibiotic drug discovery, as a universal tool to aid in
      the search for compounds that can easily penetrate bacterial cells. 

PMID- 25753588
TI  - Application value of MRI combined with positron emission tomography (PET)/CT in
      diagnosis and preoperative staging of tongue squamous cell carcinoma.
AB  - INTRODUCTION: This study aimed to compare and analyse the findings of tongue
      squamous cell carcinoma (TSCC) on MRI and positron emission tomography (PET)/CT
      and explore the diagnostic utility of combined MRI-PET/CT in the diagnosis and
      preoperative staging of TSCC. METHODS: A prospective analysis of MRI and PET/CT
      data in 18 TSCC cases was performed. Cases were comprehensively staged on MRI and
      PET/CT preoperatively according to American Joint Committee on Cancer (AJCC)
      staging criteria and confirmed by pathological results. RESULTS: The highest and
      lowest sensitivities of preoperative AJCC staging I-IV using MRI alone, PET/CT
      alone and combined MRI-PET/CT were 100.0%, 100.0% and 100.0% (stage II) and
      50.4%, 55.6% and 55.6% (stage I), respectively. The highest specificities were
      100.0%, 100.0% and 100.0% (stage II), and the highest correct rates were 100.0%,
      96.5% and 100.0% (stage II). Compared with the postoperative pathological
      staging, preoperative staging showed no significant difference for stages I-II
      and IV (P > 0.05); however, stage III showed a significant difference (P < 0.05).
      When combined MRI-PET/CT was compared with MRI alone in the accuracy of
      preoperative TSCC staging, there was no significant difference for stages I-III
      (P > 0.05), but there was a significant difference for stage IV (P < 0.05).
      CONCLUSIONS: Combined MRI and PET/CT could serve as an important tool for the
      accurate diagnosis and preoperative staging of TSCC and could improve the
      accuracy of preoperative TSCC staging.

PMID- 25753589
TI  - 'Transitions are Scary for our Kids, and They're Scary for us': Family Member and
      Youth Perspectives on the Challenges of Transitioning to Adulthood with Autism.
AB  - BACKGROUND: Adolescents with autism spectrum disorder (ASD) face many challenges
      as they age into adulthood. Because little is known about the perspectives of
      caregivers and youth during this critical transition, this study explored their
      social, educational, and vocational needs and experiences. METHOD: Two focus
      groups were conducted with youth with ASD (n = 13) and two focus groups were
      conducted with their caregivers (n = 19), where theme analysis strategies derived
      from Grounded Theory were utilized to identify themes. RESULTS: Both groups
      experienced fear and anxiety about transitioning, unmet needs were also high,
      leaving caregivers struggling to fill gaps. Most caregivers and youth reported
      lacking individualized services. Caregivers faced difficulty in motivating youth
      and creating opportunities for education and employment. Although youth have
      future goals, they were unaware of steps needed to accomplish them and hesitant
      to talk to caregivers. CONCLUSIONS: Findings indicate considerable unmet needs
      for caregivers and youth with ASD. Perspectives of both groups should be
      considered when developing programmes and educating providers.

PMID- 25753587
TI  - Biosynthesis of the antifungal haterumalide, oocydin A, in Serratia, and its
      regulation by quorum sensing, RpoS and Hfq.
AB  - Polyketides represent an important class of bioactive natural products with a
      broad range of biological activities. We identified recently a large trans
      acyltransferase (AT) polyketide synthase gene cluster responsible for the
      biosynthesis of the antifungal, anti-oomycete and antitumor haterumalide, oocydin
      A (ooc). Using genome sequencing and comparative genomics, we show that the ooc
      gene cluster is widespread within biocontrol and phytopathogenic strains of the
      enterobacteria, Serratia and Dickeya. The analysis of in frame deletion mutants
      confirmed the role of a hydroxymethylglutaryl-coenzyme A synthase cassette, three
      flavin-dependent tailoring enzymes, a free-standing acyl carrier protein and two
      hypothetical proteins in oocydin A biosynthesis. The requirement of the three
      trans-acting AT domains for the biosynthesis of the macrolide was also
      demonstrated. Expression of the ooc gene cluster was shown to be positively
      regulated by an N-acyl-L-homoserine lactone-based quorum sensing system, but
      operating in a strain-dependent manner. At a post-transcriptional level, the RNA
      chaperone, Hfq, plays a key role in oocydin A biosynthesis. The Hfq-dependent
      regulation is partially mediated by the stationary phase sigma factor, RpoS,
      which was also shown to positively regulate the synthesis of the macrolide. Our
      results reveal differential regulation of the divergently transcribed ooc
      transcriptional units, highlighting the complexity of oocydin A production. 

PMID- 25753590
TI  - Mechanical properties of different airway stents.
AB  - Airway stents improve pulmonary function and quality of life in patients
      suffering from airway obstruction. The aim of this study was to compare main
      types of stents (silicone, balloon-dilated metal, self-expanding metal, and
      covered self-expanding metal) in terms of their mechanical properties and the
      radial forces they exert on the trachea. Mechanical measurements were carried out
      using a force gauge and specially designed adaptors fabricated in our lab.
      Numerical simulations were performed for eight different stent geometries,
      inserted into trachea models. The results show a clear correlation between stent
      diameter (oversizing) and the levels of stress it exerts on the trachea. Compared
      with uncovered metal stents, metal stents that are covered with less stiff
      material exert significantly less stress on the trachea while still maintaining
      strong contact with it. The use of such stents may reduce formation of mucosa
      necrosis and fistulas while still preventing stent migration. Silicone stents
      produce the lowest levels of stress, which may be due to weak contact between the
      stent and the trachea and can explain their propensity for migration.
      Unexpectedly, stents made of the same materials exerted different stresses due to
      differences in their structure. Stenosis significantly increases stress levels in
      all stents. 

PMID- 25753591
TI  - The Epidemiology of Nonsurgical Hypoparathyroidism in Denmark: A Nationwide Case
      Finding Study.
AB  - Nonsurgical hypoparathyroidism (HypoPT) is a rare disorder most often caused by
      mutations in different genes. It is characterized by hypocalcaemia with
      inappropriately low PTH levels. Knowledge about this group of patients, including
      their mortality and morbidity, is very sparse. The aim was to identify all
      patients diagnosed with nonsurgical HypoPT in Denmark and assess their mortality
      and risk of complications. Through registers and review of individual patient
      hospital charts we identified all patients diagnosed with nonsurgical HypoPT in
      Denmark between 1977 and 2012. We assessed their mortality and morbidity by
      comparing them with a group of age- and gender-matched population-based controls.
      We identified a total of 180 patients with nonsurgical HypoPT among whom 123
      (68%) were alive at the date of follow-up (prevalence of 2.3/100,000
      inhabitants). Compared with controls, mortality was not increased, but patients
      had a significantly increased risk of renal insufficiency (hazard ratio [HR]
      6.01), cardiovascular diseases (HR 1.91), neuropsychiatric complications (HR
      2.45), infections (HR 1.94), seizures (HR 10.05), cataract (HR 4.21), and
      fractures at the upper extremities (HR 1.93). In contrast patients had
      significantly reduced risk of malignant diseases (HR 0.44). In conclusion,
      nonsurgical HypoPT is a rare disease associated with a number of complications
      that should be considered when taking care of these patients.

PMID- 25753592
TI  - Time-resolved MR angiography in wake-up stroke: an innovative application of a
      proven technique.

PMID- 25753593
TI  - Diffuse optical tomography of breast carcinoma: can tumor total hemoglobin
      concentration be considered as a new promising prognostic parameter of breast
      carcinoma?
AB  - RATIONALE AND OBJECTIVES: Diffuse optical tomography (DOT) is an emerging
      functional modality, which can reflect tumor metabolic activity and angiogenesis.
      The purpose of this exploratory study was to correlate the total hemoglobin
      concentration (THC) measured by noninvasive DOT with prognostic factors in breast
      carcinomas. MATERIALS AND METHODS: We prospectively imaged 251 breast carcinomas
      in 229 consecutive women (mean age, 51.18 +/- 12.32 years) using DOT from 2007 to
      2010. Tumor angiogenesis and metabolic activity were assessed based on
      quantitatively measured THC. The THC was correlated with prognostic factors,
      including tumor size, histopathologic classification, histologic grade, estrogen
      receptor (ER), progesterone receptor (PR), c-erbB-2, and p53. RESULTS: In
      univariate analysis, THC was significantly correlated with the following
      prognostic factors: tumor size (P < .001), histologic grade (P < .001), ER (P <
      .05), PR (P < .001), and c-erbB-2 (P < .05). THC was not associated with
      histopathologic classification (P = .170) or p53 (P = .463). On the basis of a
      stepwise multiple regression analysis, THC of invasive ductal carcinoma was
      significantly correlated with tumor size (P < .001), histologic grade (P < .001),
      and PR (P < .05). CONCLUSIONS: THC was associated with prognostic factors of
      breast carcinoma. THC may be considered as a new prognostic parameter of breast
      carcinoma and a prediction of tumor behavior and biological activity.

PMID- 25753594
TI  - Change overload and the program director.

PMID- 25753595
TI  - Clarification of the nature and use of the ACR Appropriateness Criteria in
      decision-support trials.

PMID- 25753596
TI  - Continued evolution of clinical decision support tools for guiding imaging
      utilization.

PMID- 25753597
TI  - Clinical and morphological features of collagen type III glomerulopathy: a report
      of nine cases from a single institution.
AB  - AIMS: We report nine Chinese patients with collagen type III glomerulopathy.
      METHODS AND RESULTS: Two males and seven females were studied, ranging in age
      from 21 to 67 years. Proteinuria and hypertension were the most common symptoms,
      with incidences of 88.9 and 77.8%, respectively. Two patients had abnormal renal
      function. Their histological appearances varied. Massive eosinophilic and weakly
      periodic acid-Schiff (PAS)-positive substances were deposited along the capillary
      loops and in the mesangial area in three cases, while others had thickened
      capillary walls with a chain-like structure or double-contour appearance of the
      PAS- and silver-stained sections. Immunofluorescence analysis showed the abundant
      deposition of collagen type III. Electron microscopy revealed massive scattered
      or bundle-shaped fibre-like materials in the subendothelial and mesangial areas.
      During follow-up, 44.4% of the patients suffered a doubling of serum creatinine.
      The level of serum creatinine at biopsy was an independent predictor of this
      doubled serum creatinine value. CONCLUSIONS: Collagen type III deposits in the
      subendothelial and mesangial areas. Some patients show global nodular lesions,
      while others show subtle changes only via PAS/silver staining. Proteinuria and
      hypertension are the most common symptoms, and the serum creatinine level at
      biopsy is an independent predictor of the doubling of serum creatinine during
      follow-up.

PMID- 25753598
TI  - Pulmonary blood volume measured by contrast enhanced ultrasound: a comparison
      with transpulmonary thermodilution.
AB  - BACKGROUND: Blood volume quantification is essential for haemodynamic evaluation
      guiding fluid management in anaesthesia and intensive care practice. Ultrasound
      contrast agent (UCA)-dilution measured by contrast enhanced ultrasound (CEUS) can
      provide the UCA mean transit time (MTT) between the right and left heart,
      enabling the assessment of the intrathoracic blood volume (ITBV(UCA)). The
      purpose of the present study was to investigate the agreement between UCA
      dilution using CEUS and transpulmonary thermodilution (TPTD) in vitro and in
      vivo. METHODS: In an in vitro setup, with variable flows and volumes, we injected
      a double indicator, ice-cold saline with SonoVue((r)), and performed volume
      measurements using transesophageal echo and thermodilution by PiCCO((r)). In a
      pilot study, we assigned 17 patients undergoing elective cardiac surgery for
      pulmonary blood volume (PBV) measurement using TPTD by PiCCO((r)) and ITBV by UCA
      dilution. Correlation coefficients and Bland-Altman analysis were performed for
      all volume measurements. RESULTS: In vitro, 73 experimental MTT's were obtained
      using PiCCO((r)) and UCA-dilution. The volumes by PiCCO((r)) and UCA-dilution
      correlated with true volumes; r(s)=0.96 (95% CI, 0.93-0.97; P<0.0001) and
      r(s)=0.97 (95% CI, 0.95-0.98; P<0.0001), respectively. The bias of PBV by
      PiCCO((r)) and ITBV(UCA) were -380 ml and -42 ml, respectively. In 16 patients,
      86 measurements were performed. The correlation between PBV by PiCCO((r)) and
      ITBV(UCA) was r(s)=0.69 (95% CI 0.55-0.79; P<0.0001). Bland-Altman analysis
      revealed a bias of -323 ml. CONCLUSIONS: ITBV assessment with CEUS seems a
      promising technique for blood volume measurement, which is minimally-invasive and
      bedside applicable. CLINICAL TRIAL REGISTRATION: ISRCTN90330260.

PMID- 25753599
TI  - Comments on the discordant recommendations for the use of symptomatic slow-acting
      drugs in knee osteoarthritis.
AB  - Despite the near concurrent publication by influential scientific organizations,
      there are important differences in interpretation of the evidence base and the
      conclusions derived from the recent Osteoarthritis Research Society International
      (OARSI) guidelines for the management of knee osteoarthritis, the American
      College of Rheumatology (ACR) guidelines (concerning also hip and hand
      osteoarthritis) and the algorithm recommendations by the European Society for
      Clinical and Economic Aspects of Osteoporosis and Osteoarthritis (ESCEO). This is
      particularly evident for the drug class of symptomatic slow-acting drugs in
      osteoarthritis. In this paper, we highlight these differences and try to
      understand where they derive from, proposing an evidence-based interpretation. 

PMID- 25753601
TI  - Exploratory Analysis of Power Spectrum and Functional Connectivity During Resting
      State in Young Binge Drinkers: A MEG Study.
AB  - Binge Drinking (BD) is a pattern of intermittent intensive alcohol intake which
      has spread among young adults over the last decades. Adolescence constitutes a
      critical neuromaturation period in which the brain is particularly sensitive to
      the effects of alcohol. However, little is known about how BD affects the brain
      activity. This study aimed to characterize the brain's functional organization in
      BD and non-BD young population by means of analyzing functional connectivity (FC)
      and relative power spectra (PS) profiles measured with magnetoencephalography
      (MEG) during eyes-closed resting state. Our sample composed 73 first-year
      university students (35 BDs and 38 controls). Results showed that the BD subjects
      displayed a decreased alpha FC in frontal-parietal regions, and conversely, an
      enhanced FC in the delta, theta and beta bands in fronto-temporal networks.
      Besides the FC differences, the BD group showed a decreased PS within alpha range
      and an increased PS within theta range in the brain's occipital region. These
      differences in FC and PS measurements provide new evidence of the
      neurophysiological alterations related to the alcohol neurotoxicity and could
      represent an initial sign of an anomalous neural activity caused by a BD pattern
      of alcohol consumption during youth. 

PMID- 25753600
TI  - Discrimination of schizophrenia auditory hallucinators by machine learning of
      resting-state functional MRI.
AB  - Auditory hallucinations (AH) are a symptom that is most often associated with
      schizophrenia, but patients with other neuropsychiatric conditions, and even a
      small percentage of healthy individuals, may also experience AH. Elucidating the
      neural mechanisms underlying AH in schizophrenia may offer insight into the
      pathophysiology associated with AH more broadly across multiple neuropsychiatric
      disease conditions. In this paper, we address the problem of classifying
      schizophrenia patients with and without a history of AH, and healthy control (HC)
      subjects. To this end, we performed feature extraction from resting state
      functional magnetic resonance imaging (rsfMRI) data and applied machine learning
      classifiers, testing two kinds of neuroimaging features: (a) functional
      connectivity (FC) measures computed by lattice auto-associative memories (LAAM),
      and (b) local activity (LA) measures, including regional homogeneity (ReHo) and
      fractional amplitude of low frequency fluctuations (fALFF). We show that it is
      possible to perform classification within each pair of subject groups with high
      accuracy. Discrimination between patients with and without lifetime AH was
      highest, while discrimination between schizophrenia patients and HC participants
      was worst, suggesting that classification according to the symptom dimension of
      AH may be more valid than discrimination on the basis of traditional diagnostic
      categories. FC measures seeded in right Heschl's gyrus (RHG) consistently showed
      stronger discriminative power than those seeded in left Heschl's gyrus (LHG), a
      finding that appears to support AH models focusing on right hemisphere
      abnormalities. The cortical brain localizations derived from the features with
      strong classification performance are consistent with proposed AH models, and
      include left inferior frontal gyrus (IFG), parahippocampal gyri, the cingulate
      cortex, as well as several temporal and prefrontal cortical brain regions.
      Overall, the observed findings suggest that computational intelligence approaches
      can provide robust tools for uncovering subtleties in complex neuroimaging data,
      and have the potential to advance the search for more neuroscience-based criteria
      for classifying mental illness in psychiatry research. 

PMID- 25753602
TI  - Inverse association of des-acyl ghrelin with worksite blood pressure in
      overweight/obese male workers.
AB  - BACKGROUND: Job strain, defined as a combination of high job demands and low job
      control, has been reported to elevate blood pressure (BP) during work. Meanwhile,
      a recent experimental study showed that ghrelin blunted the BP response to such
      mental stress. In the present study, we examined the hypothesis that des-acyl
      ghrelin may have some beneficial effects on worksite BP through modulating the BP
      response to work-related mental stress, i.e., job strain. METHODS: Subjects were
      34 overweight/obese male day-shift workers (mean age 41.7 +/- 6.7 years). No
      subjects had received any anti-hypertensive medication. A 24-h ambulatory BP
      monitoring was recorded every 30 min on a regular working day. The average BP was
      calculated for Work BP, Morning BP, and Home BP. Job strain was assessed using
      the short version of the Japanese Job Content Questionnaire. RESULTS: Des-acyl
      ghrelin showed significant inverse correlations with almost all BPs except
      Morning SBP, Morning DBP, and Home DBP. In multiple regression analysis, des-acyl
      ghrelin inversely correlated with Work SBP after adjusting for confounding
      factors. Des-acyl ghrelin was also negatively associated with BP changes from
      Sleep to Morning, Sleep to Work, and Sleep to Home. CONCLUSIONS: Des-acyl ghrelin
      was inversely associated with Worksite BP, suggesting a unique beneficial effect
      of des-acyl ghrelin on Worksite BP in overweight/obese male day-shift workers.

PMID- 25753603
TI  - Sedentary Behavior in Individuals With Diabetic Chronic Kidney Disease and
      Maintenance Hemodialysis.
AB  - OBJECTIVE: The objective of this study was to examine whether more advanced
      kidney failure is associated with sedentary behavior and whether demographics,
      comorbidity, nutritional, and inflammatory markers explain this association.
      DESIGN: Observational study. SETTING: Outpatients recruited from outpatient
      clinics and dialysis units. SUBJECTS: One hundred sixty patients with chronic
      kidney disease (CKD) or receiving maintenance hemodialysis (MHD). METHODS:
      Standardized questionnaires including Baecke physical activity questionnaire,
      standardized anthropometry examination, and blood draw. MAIN OUTCOME MEASURE:
      Sedentary behavior (defined as answering "very often" for "during leisure time I
      watch television" or answering "never" for "during leisure time I walk") and
      being physically active (top 25th percentile of the total Baecke score). RESULTS:
      Nineteen percent of CKD and 50% of MHD patients were sedentary (P < .001) and
      38.8% of CKD and 11.3% of MHD patients were physically active. In separate
      multivariable logistic regression models, compared with CKD patients, MHD
      patients were more sedentary (odds ratio 3.84; 95% confidence interval, 1.18
      12.51) and less physically active (odds ratio 0.07; 95% confidence interval 0.01
      0.40) independent of demographics, comorbidity, smoking, body size, serum high
      sensitivity C-reactive protein (hsCRP) and albumin. Congestive heart failure,
      peripheral vascular disease, and higher body mass index were independently
      associated with sedentary behavior, whereas younger age, lower body mass index,
      lower serum hsCRP, and higher serum albumin were associated with being physically
      active. CONCLUSIONS: Sedentary behavior is highly prevalent among diabetic CKD or
      MHD patients. The strong association of MHD status with sedentary behavior is not
      explained by demographics, smoking, comorbidity, nutritional, and inflammatory
      markers. Interventions targeting obesity might improve sedentary behavior and
      physical activity, whereas interventions targeting inflammation might improve
      physical activity in these populations.

PMID- 25753605
TI  - Practicalities of Using the Nutrition Care Process in Research.

PMID- 25753604
TI  - The Effects of Parenteral Amino Acid Therapy on Protein Carbamylation in
      Maintenance Hemodialysis Patients.
AB  - OBJECTIVE: Protein carbamylation is a urea-driven post-translational protein
      modification associated with mortality in dialysis patients. Free amino acids
      (AAs) are competitive inhibitors of protein carbamylation and animal studies
      suggest increasing AA concentrations reduces carbamylation burden. We
      hypothesized that AA therapy in maintenance hemodialysis patients would reduce
      carbamylation, carrying the potential to improve clinical outcomes. DESIGN:
      Prospective pilot clinical trial (NCT1612429). SETTING: The study was conducted
      from March 2013 to March 2014 in outpatient dialysis facilities in the Boston
      metropolitan area. SUBJECTS AND INTERVENTION: We enrolled 23 consecutively
      consenting hemodialysis subjects, infusing the first 12 individuals with 250 cc
      of AAs 3 times per week postdialysis over 8 weeks. The remaining 11 subjects
      served as controls. MAIN OUTCOME MEASURE: Change in carbamylated albumin (C-Alb),
      a measure of total body carbamylation burden, between baseline and 8 weeks was
      the primary outcome. RESULTS: The treated and control groups had similar clinical
      characteristics and similar baseline C-Alb levels (mean +/- SE 9.5 +/- 2.4 and
      9.3 +/- 1.3 mmol/mol, respectively; P = .61). The treated arm showed a
      significant reduction in C-Alb compared with controls at 4 weeks (8.4% reduction
      in the treated arm vs. 4.3% increase in controls; P = .03) and the effect was
      greater by 8 weeks (15% reduction in the treated vs. 1% decrease in controls; P =
      .01). CONCLUSION: In this pilot study, AA therapy appeared safe and effective at
      reducing C-Alb levels in hemodialysis patients compared with no treatment. The
      impact of reduced protein carbamylation on clinical outcomes should be further
      investigated.

PMID- 25753606
TI  - Broadband nonreciprocal quadrupolarization-induced asymmetric transmission (Q-AT)
      in plasmonic nanoparticle aggregates.
AB  - Non-reciprocal asymmetric transmission, i.e., the dependence of optical
      transmittance on the direction of light propagation in the material, can be used
      in optical isolators or photonic circuits. Broadband asymmetric transmission is
      observed in near-field coupled aggregates of small plasmonic nanoparticles, even
      for unpolarized light. Non-reciprocity is demonstrated and, using a
      phenomenological model, induced electric quadrupole moments are identified as the
      root cause of the effect. 

PMID- 25753607
TI  - [Risk factors for ischemic heart disease in males in the prime of life: An eight
      year follow-up study].
AB  - OBJECTIVE: In order to prevent ischemic heart disease in working adult males, we
      analyzed risk factors by age groups based on data from an eight-year follow-up
      study of male employees enrolled in the Denso Health Insurance Program. SUBJECTS
      AND METHODS: Of the 27,945 male employees aged 30 to 55 enrolled in the program
      in 2003, the data of 19,742 (70.6%) who underwent regular health checkups were
      analyzed. Information obtained from health insurance claims for hospitalization
      and cause of death from discontinuation data were used to analyze risk factors
      for ischemic heart disease by age group. Hazard ratios and 95% confidence
      intervals were estimated from Cox proportional-hazards models. RESULTS: In males
      aged 30-39 years, a BMI of 25.0-27.5 was associated with a 2.21 higher risk of
      ischemic heart disease (95%CI: 1.01-4.84) than those not overweight (BMI of
      <25.0); LDL of 160 mg/dl or more was associated with a 3.85 higher risk
      (95%CI:1.62-9.14) than LDL of less than 120 mg/dl; and FPG of 160 mg/dl or more
      was associated with a 6.43 higher risk (95%CI: 1.02-40.63) than a FPG of less
      than 110 mg/dl. For males aged 40-55 years, higher LDL was a risk factor of
      ischemic heart disease (1.95 (95%CI: 1.28-2.98) and 1.97 (95%CI: 1.34-2.90) for
      LDL of more than 160 mg/dl and 140-159 mg/dl, respectively), compared to those
      with LDL of less than 120 mg/dl. In the same age group, compared to those
      unaffected, the risk of ischemic heart disease was 1.94 times higher (95%CI: 1.27
      2.97) and 1.61 times higher (95%CI: 1.08-2.40) for those treated for hypertension
      and hyperlipidemia, respectively. Furthermore, compared to non-smokers, those
      smoking more than 20 cigarettes a day had 3.12 higher risk (95%CI: 1.21-8.06) and
      1.81 higher risk (95%CI: 1.25-2.62) of ischemic heart disease in the 30-39 and 40
      55 years age groups, respectively. Interaction effects with age group were not
      significant. DISCUSSION: In males aged 30-39 years having a high BMI, LDL, FPG,
      and smoking more than 20 cigarettes increased the risk of ischemic heart disease.
      For males aged 40-55 years taking medication for hypertension and hyperlipidemia
      increased the risk. To prevent ischemic heart disease during the prime of life,
      offering support for weight control and stopping smoking is necessary in younger
      age groups. Moreover, implementing a long-term risk management plan to prevent
      the onset of hypertension, diabetes, or hyperlipidemia is also important.

PMID- 25753608
TI  - [Background data of spontaneous tumors in F344/DuCrlCrlj rats].
AB  - INTRODUCTION: We investigated the 2-year survival rate and incidence of
      spontaneous tumors in F344/DuCrlCrlj rats used in carcinogenicity studies of
      chemical substances. Records for animals used in the control groups of
      carcinogenicity studies which were conducted during the last 10 years were
      obtained from the database of the Japan Bioassay Research Center (JBRC). Six
      hundred ninety-nine males and 550 females were used in 14 and 11 inhalation
      studies, respectively, and 500 animals of each sex were used in 10 male and 10
      female oral studies. METHODS: In each study, SPF (specific pathogen free) animals
      were housed for 2 years (104 weeks) as control groups in the carcinogenicity
      studies. All animals underwent necropsy and histopathological examination. Each
      study was conducted in accordance with the Good Laboratory Practice. RESULTS: The
      incidence of interstitial cell tumors was highest in both inhalation studies and
      oral studies (inhalation studies 86.1%, oral studies 68.6%). Tumors which had an
      incidence of 6% or higher were adenoma of the pituitary, C-cell adenoma of the
      thyroid, and mononuclear cell leukemia (LGL leukemia) of the spleen in male and
      female rats; fibroma of the subcutaneous tissue, adrenal pheochromocytoma, and
      islet cell adenoma of the pancreas in male rats; and endometrial stromal polyps
      and fibroadenoma of the mammary gland in female rats. Tumors other than the above
      had rare incidence rates. A clear difference in the incidence of spontaneous
      tumors was not observed between the inhalation and oral studies. The incidences
      of spontaneous tumors in control groups of previous oral studies are similar to
      our findings. There are no other reports of the spontaneous tumor incidence in
      the control groups of inhalation studies using F344/DuCrlCrlj rats. The 2-year
      survival rate was about 77% in both the inhalation and oral studies, and a gender
      difference was not observed. The F344/DuCrlCrlj rats used at JBRC had a higher 2
      year survival rate than F344/N rats. This difference is possibly due to the low
      incidence of LGL leukemia in the F344/DuCrlCrlj rat. CONCLUSIONS: The incidences
      of spontaneous tumors in F344/DuCrlCrlj rats used in control groups of both
      inhalation and oral studies during the last 10 years at JBRC are similar to each
      other and similar to those reported in other studies. This is the first report on
      the incidence of spontaneous tumors in inhalation studies and contributes to the
      toxicological evaluation of studies using F344/DuCrlCrlj rats.

PMID- 25753609
TI  - Job Profiles of Biomedical Informatics Graduates. Results of a Graduate Survey.
AB  - BACKGROUND: Biomedical informatics programs exist in many countries. Some
      analyses of the skills needed and of recommendations for curricular content for
      such programs have been published. However, not much is known of the job profiles
      and job careers of their graduates. OBJECTIVES: To analyse the job profiles and
      job careers of 175 graduates of the biomedical informatics bachelor and master
      program of the Tyrolean university UMIT. METHODS: Survey of all biomedical
      informatics students who graduated from UMIT between 2001 and 2013. RESULTS:
      Information is available for 170 graduates. Eight percent of graduates are male.
      Of all bachelor graduates, 86% started a master program. Of all master graduates,
      36% started a PhD. The job profiles are quite diverse: at the time of the survey,
      35% of all master graduates worked in the health IT industry, 24% at research
      institutions, 9% in hospitals, 9% as medical doctors, 17% as informaticians
      outside the health care sector, and 6% in other areas. Overall, 68% of the
      graduates are working as biomedical informaticians. The results of the survey
      indicate a good job situation for the graduates. CONCLUSIONS: The job
      opportunities for biomedical informaticians who graduated with a bachelor or
      master degree from UMIT seem to be quite good. The majority of graduates are
      working as biomedical informaticians. A larger number of comparable surveys of
      graduates from other biomedical informatics programs would help to enhance our
      knowledge about careers in biomedical informatics.

PMID- 25753610
TI  - Rethinking family-centred care for the child and family in hospital.
AB  - AIMS AND OBJECTIVES: This paper presents and discusses an alternative model of
      family-centred care (FCC) that focuses on optimising the health and developmental
      outcomes of children through the provision of appropriate support to the child's
      family. BACKGROUND: The relevance, meaning and effectiveness of FCC have been
      challenged recently. Studies show that parents in hospital often feel
      unsupported, judged by hospital staff and uncertain about what care they should
      give to their child. With no convincing evidence relating FCC to improved child
      health outcomes, it has been suggested that FCC should be replaced with a new
      improved model to guide the care of children in hospital. DESIGN: This
      integrative review discusses theory and evidence-based literature that supports
      the practice of an alternative model of FCC that is focused on the health and
      developmental outcomes of children who are seriously ill, rather than the
      organisational requirements of children's hospitals. METHODS: Theories and
      research findings in a wide range of disciplines including epidemiology,
      psychology, sociology, anthropology and neuroscience were accessed for this
      discussion. Nursing literature regarding partnership building, communication and
      FCC was also accessed. DISCUSSION: This paper discusses the benefits of applying
      a bioecological model of human development, the family and community resource
      framework, the concepts of allostatic load and biological embedding, empowerment
      theory, and the nurse-family partnership model to FCC. CONCLUSION: While there is
      no direct evidence showing that the implementation of this alternative model of
      FCC in the hospital setting improves the health and developmental outcomes of
      children who are seriously ill, there is a great deal of evidence from community
      nursing practice that suggests it is very likely to do so. RELEVANCE TO CLINICAL
      PRACTICE: Application of these theoretical concepts to practice has the potential
      to underpin a theory of nursing that is relevant for all nurses irrespective of
      the age of those they care for and the settings within which they work.

PMID- 25753611
TI  - Potential utilization of expanded function dental auxiliaries to place
      restoratives.
AB  - OBJECTIVES: The Affordable Care Act is predicted to increase dental benefits
      coverage for millions of Americans. Utilization of expanded function dental
      auxiliaries (EFDAs) can contribute to increased workforce capacity. Iowa
      currently allows EFDAs to perform certain nonrestorative procedures. This study
      investigated dentists' willingness to use auxiliaries for restorative procedures
      in order inform recent discussions about expanding scope of practice for EFDAs to
      include such procedures. METHODS: This study examined responses from 677 primary
      care dentists who responded to the 2013 Survey of Iowa Dentists (response rate =
      59 percent). The authors performed univariate and bivariate analyses (chi(2) and
      t-tests) to examine characteristics of dentists who indicated willingness to
      utilize an auxiliary for newly proposed restorative functions. RESULTS: Thirty
      seven percent of respondents indicated they would delegate at least one of the
      newly proposed restorative functions to an auxiliary. Pediatric dentists were
      significantly more likely to be willing to delegate (P = 0.042). Placing
      stainless steel crowns was most acceptable (31.9 percent of respondents),
      followed by amalgam restorations (22.3 percent), and composites (18.6 percent).
      CONCLUSIONS: Many dentists are willing to delegate reversible restorative
      procedures. Increasing scope of practice for auxiliaries may increase capacity of
      the existing dental workforce and improve access for newly insured populations.
      Expanding scope of practice for dental auxiliaries offers a viable mechanism to
      rapidly increase states' dental capacity in response to rising demands for dental
      care, including newly insured Medicaid populations.

PMID- 25753612
TI  - Piloting an abbreviated dignity therapy intervention using a legacy-building web
      portal for adults with terminal cancer: a feasibility and acceptability study.

PMID- 25753613
TI  - Full 40: the quest to study gestational age and child development with big data.

PMID- 25753615
TI  - Prevalence, Antimicrobial Resistance and Risk Factors for Thermophilic
      Campylobacter Infections in Symptomatic and Asymptomatic Humans in Tanzania.
AB  - The genus Campylobacter comprises members known to be a leading cause of
      foodborne gastrointestinal illness worldwide. A study was conducted to determine
      the epidemiology and antimicrobial resistance of Campylobacter in humans in
      Morogoro, Eastern Tanzania. Isolation of Campylobacter from stool specimens
      adopted the Cape Town protocol. Campylobacter isolates were preliminarily
      identified by conventional phenotypic tests and subsequently confirmed by matrix
      assisted laser desorption/ionization-time-of-flight (MALDI-TOF) mass spectrometry
      and polymerase chain reaction. Antimicrobial resistance testing employed the disc
      diffusion method. A small proportion of the test isolates was also subjected to
      agar dilution method. Risk factors for human illness were determined in an
      unmatched case-control study. Thermophilic Campylobacter were isolated from 11.4%
      of the screened individuals (n = 1195). The agreement between PCR and MALDI-TOF
      was perfect (kappa = 1.0). Symptomatics and young individuals were infected with
      higher numbers than asymptomatic and adults, respectively. The majority (84.6%)
      of the isolates were C. jejuni and the remaining were C. coli. Isolates had
      highest resistance (95.6%) for colistin sulphate and lowest for ciprofloxacin
      (22.1%). The rates of resistance for other antibiotics (azithromycin,
      erythromycin, tetracycline, cephalothin, gentamycin, nalidixic acid, ampicillin,
      amoxycillin, norfloxacin, chloramphenicol) ranged from 44.1% to 89%. Comparison
      between disc diffusion and agar dilution methods indicated a good correlation,
      and the tests were in agreement to each other (kappa >= 0.75). Human illness was
      found to be associated with young age and consumption of chicken meat and pre
      prepared salad. Our data indicate the presence of antibiotic-resistant
      thermophilic Campylobacter in humans in the study area. There is a need for
      routine investigation of the presence of the organisms in gastroenteritis
      aetiology, including determination of their antibiotic susceptibilities.

PMID- 25753614
TI  - Quantitative assessment of amide proton transfer (APT) and nuclear overhauser
      enhancement (NOE) imaging with extrapolated semi-solid magnetization transfer
      reference (EMR) signals: Application to a rat glioma model at 4.7 Tesla.
AB  - PURPOSE: To quantify amide proton transfer (APT) and nuclear Overhauser
      enhancement (NOE) contributions to in vivo chemical exchange saturation transfer
      MRI signals in tumors. THEORY AND METHODS: Two-pool (free water and semi-solid
      protons) and four-pool (free water, semi-solid, amide, and upfield NOE-related
      protons) tissue models combined with the super-Lorentzian lineshape for semi
      solid protons were used to fit wide and narrow frequency-offset magnetization
      transfer (MT) data, respectively. Extrapolated semi-solid MT signals at 3.5 and 
      3.5 ppm from water were used as reference signals to quantify APT and NOE,
      respectively. Six glioma-bearing rats were scanned at 4.7 Tesla. Quantitative APT
      and NOE signals were compared at three saturation power levels. RESULTS: The
      observed APT signals were significantly higher in the tumor (center and rim) than
      in the contralateral normal brain tissue at all saturation powers, and were the
      major contributor to the APT-weighted image contrast (based on MT asymmetry
      analysis) between the tumor and the normal brain tissue. The NOE (a positive
      confounding factor) enhanced this APT-weighted image contrast. The fitted amide
      pool sizes were significantly larger, while the NOE-related pool sizes were
      significantly smaller in the tumor than in the normal brain tissue. CONCLUSION:
      The extrapolated semi-solid magnetization transfer reference provides a
      relatively accurate approach for quantitatively measuring pure APT and NOE
      signals.

PMID- 25753617
TI  - Renal impairment among postmenopausal women with osteoporosis from a large health
      plan in Israel.
AB  - Bisphosphonates are a first-line treatment for osteoporosis but require adequate
      renal function. We estimated the prevalence of renal impairment among
      osteoporotic women in Israeli. Approximately 2.3 % of women had renal impairment
      at a level that makes them inappropriate for bisphosphonate use, demonstrating
      the need for alternative therapies for osteoporosis treatment. PURPOSE: The
      purpose of this study is to estimate the prevalence of renal impairment among
      postmenopausal osteoporotic women within a large Israeli health plan. METHODS:
      This was a retrospective analysis of Maccabi electronic medical records,
      including Israeli women aged >=55 with either an osteoporosis diagnosis or
      osteoporosis-related fracture between January 1, 2007, and December 31, 2011. The
      estimated glomerular filtration rate (eGFR), which was calculated from the lowest
      serum creatinine levels reported during the study period, was used to classify
      stage 1-5 renal impairment: normal >=90, mild 60-89, moderate 30-59, severe 15
      29, and failure <15 mL/min/1.73 m(2), respectively. Outcomes were distributions
      of renal impairment across the study population and stratified by age and
      osteoporosis-defining event. RESULTS: A total of 15,608 patients met all
      eligibility criteria. Patients with stage 1-5 renal function accounted for 25.2,
      54.9, 18.5, 1.2, and 0.3 %, respectively, of all patients. Of osteoporotic
      patients, 2.3 % had eGFR levels (<35 mL/min/1.73 m(2)) that make them
      inappropriate for bisphosphonate use. This rate was 1.6 % among patients with an
      osteoporosis diagnosis and 3.8 % among patients with osteoporosis-related
      fracture. Within the group of renally impaired patients, older patients were
      overrepresented. Of the fracture group, patients with hip fractures had a higher
      prevalence of renal dysfunction (9.3 %) than those having vertebral fractures
      (3.2 %) or other fractures (2.0 %). CONCLUSIONS: Among postmenopausal women with
      osteoporosis, 2.3 % had renal impairment which makes them inappropriate for
      bisphosphonate use in Israel.

PMID- 25753618
TI  - Fractionated carbon dioxide laser therapy as treatment of mild rhinophyma: report
      of three cases.
AB  - Rhinophyma is a bothersome condition of the nose that is regarded as a
      manifestation of rosacea (subtype 3). Whereas the efficacy of medical treatments,
      including antibiotics and retinoids, is often dissatisfying, conventional
      invasive procedures are limited by their unfavorable side effect profile. We
      present three patients who were treated by a minimally invasive approach using
      fractionated carbon dioxide (CO2) laser therapy, showing variable response. We
      observed that fractionated CO2 laser therapy may improve patient-reported outcome
      in some patients with mild rhinophyma and is associated with a relatively
      favorable side effect profile compared with conventional surgical techniques.

PMID- 25753619
TI  - Lysosomal Targeting of Cystinosin Requires AP-3.
AB  - Cystinosin is a lysosomal cystine transporter defective in cystinosis, an
      autosomal recessive lysosomal storage disorder. It is composed of seven
      transmembrane (TM) domains and contains two lysosomal targeting motifs: a
      tyrosine-based signal (GYDQL) in its C-terminal tail and a non-classical motif in
      its fifth inter-TM loop. Using the yeast two-hybrid system, we showed that the
      GYDQL motif specifically interacted with the MU subunit of the adaptor protein
      complex 3 (AP-3). Moreover, cell surface biotinylation and total internal
      reflection fluorescence microscopy revealed that cystinosin was partially
      mislocalized to the plasma membrane (PM) in AP-3-depleted cells. We generated a
      chimeric CD63 protein to specifically analyze the function of the GYDQL motif.
      This chimeric protein was targeted to lysosomes in a manner similar to cystinosin
      and was partially mislocalized to the PM in AP-3 knockdown cells where it also
      accumulated in the trans-Golgi network and early endosomes. Together with the
      fact that the surface levels of cystinosin and of the CD63-GYDQL chimeric protein
      were not increased when clathrin-mediated endocytosis was impaired, our data show
      that the tyrosine-based motif of cystinosin is a 'strong' AP-3 interacting motif
      responsible for lysosomal targeting of cystinosin by a direct intracellular
      pathway. 

PMID- 25753620
TI  - A worrying trend in weight-adjusted paediatric antibiotic use in a Norwegian
      tertiary care hospital.
AB  - AIM: The World Health Organization recommends the defined daily dose (DDD) as the
      standard unit of measurement for antibiotic use, but this is not applicable in
      children. We aimed to assess paediatric antibiotic use in a Norwegian tertiary
      care hospital using a novel weight-adjusted method. METHODS: We obtained
      antibiotic purchase data from the hospital pharmacy and administrative data for
      all admissions from 2002 to 2009 to the paediatric wards at Oslo University
      Hospital, Rikshospitalet. Recommended daily doses per 100 kg days (RDDs/kg days)
      were calculated based on national guidelines for paediatric antibiotic use,
      length of stay and estimated weight for sex and age using national growth
      references. RESULTS: Total antibiotic use increased significantly from 51.8 to
      65.5 RDDs/100 kg days. We found statistically significant annual increases in the
      consumption of carbapenems (18.0%), third-generation cephalosporins (6.0%) and
      imidazole derivatives (6.6%) and a considerable difference between total
      antibiotic use measured in RDDs/100 kg days and DDDs/100 bed days for neonates.
      CONCLUSION: Weight-adjusted antibiotic use provided a more meaningful description
      of the quantities of antibiotics consumed than DDDs/100 bed days, particularly
      for neonates. Total antibiotic use, use of meropenem, third-generation
      cephalosporins and imidazole derivatives increased significantly despite low
      prevalence of antibiotic-resistant pathogens.

PMID- 25753621
TI  - Micro-MoS2 with excellent reversible sodium-ion storage.
AB  - Low storage capacity and poor cycling stability are the main drawbacks of the
      electrode materials for sodium-ion (Na-ion) batteries, due to the large radius of
      the Na ion. Here we show that micro-structured molybdenum disulfide (MoS2 ) can
      exhibit high storage capacity and excellent cycling and rate performances as an
      anode material for Na-ion batteries by controlling its intercalation depth and
      optimizing the binder. The former method is to preserve the layered structure of
      MoS2 , whereas the latter maintains the integrity of the electrode during
      cycling. A reversible capacity of 90 mAh g(-1) is obtained on a potential plateau
      feature when less than 0.5 Na per formula unit is intercalated into micro-MoS2 .
      The fully discharged electrode with sodium alginate (NaAlg) binder delivers a
      high reversible capacity of 420 mAh g(-1) . Both cells show excellent cycling
      performance. These findings indicate that metal chalcogenides, for example, MoS2
      , can be promising Na-storage materials if their operation potential range and
      the binder can be appropriately optimized.

PMID- 25753616
TI  - Disentangling the complex evolutionary history of the Western Palearctic blue
      tits (Cyanistes spp.) - phylogenomic analyses suggest radiation by multiple
      colonization events and subsequent isolation.
AB  - Isolated islands and their often unique biota continue to play key roles for
      understanding the importance of drift, genetic variation and adaptation in the
      process of population differentiation and speciation. One island system that has
      inspired and intrigued evolutionary biologists is the blue tit complex (Cyanistes
      spp.) in Europe and Africa, in particular the complex evolutionary history of the
      multiple genetically distinct taxa of the Canary Islands. Understanding
      Afrocanarian colonization events is of particular importance because of recent
      unconventional suggestions that these island populations acted as source of the
      widespread population in mainland Africa. We investigated the relationship
      between mainland and island blue tits using a combination of Sanger sequencing at
      a population level (20 loci; 12 500 nucleotides) and next-generation sequencing
      of single population representatives (>3 200 000 nucleotides), analysed in
      coalescence and phylogenetic frameworks. We found (i) that Afrocanarian blue tits
      are monophyletic and represent four major clades, (ii) that the blue tit complex
      has a continental origin and that the Canary Islands were colonized three times,
      (iii) that all island populations have low genetic variation, indicating low long
      term effective population sizes and (iv) that populations on La Palma and in
      Libya represent relicts of an ancestral North African population. Further,
      demographic reconstructions revealed (v) that the Canary Islands, conforming to
      traditional views, hold sink populations, which have not served as source for
      back colonization of the African mainland. Our study demonstrates the importance
      of complete taxon sampling and an extensive multimarker study design to obtain
      robust phylogeographical inferences.

PMID- 25753622
TI  - Cystic sebaceous tumour with no evidence of Muir-Torre syndrome.

PMID- 25753623
TI  - A comparison of 1D analytical model and 3D finite element analysis with
      experiments for a rosen-type piezoelectric transformer.
AB  - This article is dedicated to the study of Piezoelectric Transformers (PTs), which
      offer promising solutions to the increasing need for integrated power electronics
      modules within autonomous systems. The advantages offered by such transformers
      include: immunity to electromagnetic disturbances; ease of miniaturisation for
      example, using conventional micro fabrication processes; and enhanced performance
      in terms of voltage gain and power efficiency. Central to the adequate
      description of such transformers is the need for complex analytical modeling
      tools, especially if one is attempting to include combined contributions due to
      (i) mechanical phenomena owing to the different propagation modes which differ at
      the primary and secondary sides of the PT; and (ii) electrical phenomena such as
      the voltage gain and power efficiency, which depend on the electrical load. The
      present work demonstrates an original one-dimensional (1D) analytical model,
      dedicated to a Rosen-type PT and simulation results are successively compared
      against that of a three-dimensional (3D) Finite Element Analysis (COMSOL
      Multiphysics software) and experimental results. The Rosen-type PT studied here
      is based on a single layer soft PZT (P191) with corresponding dimensions 18 mm *
      3 mm * 1.5 mm, which operated at the second harmonic of 176 kHz. Detailed
      simulational and experimental results show that the presented 1D model predicts
      experimental measurements to within less than 10% error of the voltage gain at
      the second and third resonance frequency modes. Adjustment of the analytical
      model parameters is found to decrease errors relative to experimental voltage
      gain to within 1%, whilst a 2.5% error on the output admittance magnitude at the
      second resonance mode were obtained. Relying on the unique assumption of one
      dimensionality, the present analytical model appears as a useful tool for Rosen
      type PT design and behavior understanding.

PMID- 25753624
TI  - Contextual and individual determinants of dental pain in preschool children.
AB  - OBJECTIVES: Despite growing interest on dental pain in children, there are very
      few studies on its prevalence and determinants among preschool children. The
      objective of this study was to assess prevalence of dental pain and associated
      individual and contextual factors in 5 year-old Brazilian children. METHODS: This
      cross-sectional study used primary data from the 2010 National Survey of Oral
      Health, carried out in capital cities and a sample of country towns. Participants
      were 7280 5-year-olds, who were examined in their homes and whose parents
      answered a questionnaire. Dependent variable was report of dental pain in the
      last 6 months. Independent variables were contextual (city level) socioeconomic
      factors, and individual (child) sociodemographic and oral health-related
      variables. Data analysis included hierarchized Poisson regression models, using a
      multilevel approach and prevalence rate (PR) estimates. RESULTS: The prevalence
      of dental pain was 22.0% (95% CI 19.1-25.2). It was higher among those living in
      cities with lower human development index (PR 0.07; 95% CI 0.02-0.22) and with a
      higher percentage of their population with an incomplete primary education (PR
      1.03; 95% CI 1.01-1.06). Indigenous children had prevalence of dental pain 1.97
      times higher (95% CI 1.19-3.26) than those of white colour. Families with monthly
      incomes of U$ 218.00 or less and between U$ 219.00 and U$ 656.00 had,
      respectively, a prevalence of dental pain 2.67 (95% CI 1.33-5.32) and 2.11 (95%
      CI 1.03-4.32) times higher than families with highest income level. For each unit
      increase in the number of dwellers per bedroom, there was a 14% increase in the
      probability of having pain. Children with caries experience had a 3.45 (95% CI
      2.58-4.62) higher prevalence of pain than caries-free individuals. CONCLUSION:
      Dental pain prevalence in Brazilian preschool children was high and influenced by
      contextual and individual factors.

PMID- 25753625
TI  - Structural characterization of an alternative mode of tigecycline binding to the
      bacterial ribosome.
AB  - Although both tetracycline and tigecycline inhibit protein synthesis by
      sterically hindering the binding of tRNA to the ribosomal A site, tigecycline
      shows increased efficacy in both in vitro and in vivo activity assays and escapes
      the most common resistance mechanisms associated with the tetracycline class of
      antibiotics. These differences in activities are attributed to the tert-butyl
      glycylamido side chain found in tigecycline. Our structural analysis by X-ray
      crystallography shows that tigecycline binds the bacterial 30S ribosomal subunit
      with its tail in an extended conformation and makes extensive interactions with
      the 16S rRNA nucleotide C1054. These interactions restrict the mobility of C1054
      and contribute to the antimicrobial activity of tigecycline, including its
      resistance to the ribosomal protection proteins. 

PMID- 25753627
TI  - Identification of aminoglycoside-resistant Pseudomonas aeruginosa producing RmtG
      16S rRNA methyltransferase in a cystic fibrosis patient.

PMID- 25753626
TI  - Impact of antimalarial treatment and chemoprevention on the drug sensitivity of
      malaria parasites isolated from ugandan children.
AB  - Changing treatment practices may be selecting for changes in the drug sensitivity
      of malaria parasites. We characterized ex vivo drug sensitivity and parasite
      polymorphisms associated with sensitivity in 459 Plasmodium falciparum samples
      obtained from subjects enrolled in two clinical trials in Tororo, Uganda, from
      2010 to 2013. Sensitivities to chloroquine and monodesethylamodiaquine varied
      widely; sensitivities to quinine, dihydroartemisinin, lumefantrine, and
      piperaquine were generally good. Associations between ex vivo drug sensitivity
      and parasite polymorphisms included decreased chloroquine and
      monodesethylamodiaquine sensitivity and increased lumefantrine and piperaquine
      sensitivity with pfcrt 76T, as well as increased lumefantrine sensitivity with
      pfmdr1 86Y, Y184, and 1246Y. Over time, ex vivo sensitivity decreased for
      lumefantrine and piperaquine and increased for chloroquine, the prevalences of
      pfcrt K76 and pfmdr1 N86 and D1246 increased, and the prevalences of pfdhfr and
      pfdhps polymorphisms associated with antifolate resistance were unchanged. In
      recurrent infections, recent prior treatment with artemether-lumefantrine was
      associated with decreased ex vivo lumefantrine sensitivity and increased
      prevalence of pfcrt K76 and pfmdr1 N86, 184F, and D1246. In children assigned
      chemoprevention with monthly dihydroartemisinin-piperaquine with documented
      circulating piperaquine, breakthrough infections had increased the prevalence of
      pfmdr1 86Y and 1246Y compared to untreated controls. The noted impacts of therapy
      and chemoprevention on parasite polymorphisms remained significant in
      multivariate analysis correcting for calendar time. Overall, changes in parasite
      sensitivity were consistent with altered selective pressures due to changing
      treatment practices in Uganda. These changes may threaten the antimalarial
      treatment and preventive efficacies of artemether-lumefantrine and
      dihydroartemisinin-piperaquine, respectively.

PMID- 25753628
TI  - Population pharmacokinetics and Monte Carlo dosing simulations of meropenem
      during the early phase of severe sepsis and septic shock in critically ill
      patients in intensive care units.
AB  - Pathophysiological changes during the early phase of severe sepsis and septic
      shock in critically ill patients, resulting in altered pharmacokinetic (PK)
      patterns for antibiotics, are important factors influencing therapeutic success.
      The aims of this study were (i) to reveal the population PK parameters and (ii)
      to assess the probability of target attainment (PTA) for meropenem. The PK
      studies were carried out following administration of 1 g of meropenem every 8 h
      during the first 24 h of severe sepsis and septic shock in nine patients, and a
      Monte Carlo simulation was performed to determine the PTA of achieving 40%
      exposure time during which the free plasma drug concentration remains above the
      MIC (fT>MIC) and 80% fT>MIC. The volume of distribution (V) and total clearance
      (CL) of meropenem in these patients were 23.7 liters and 7.82 liters/h,
      respectively. For pathogens with MICs of 4 MUg/ml, the PTAs of 40% fT>MIC
      following administration of meropenem as a 1-h infusion of 1 g every 8 h and a 4
      h infusion of 0.5 g every 8 h were 92.52% and 90.29%, respectively. For pathogens
      with MICs of 2 MUg/ml in immunocompromised hosts, the PTAs of 80% fT>MIC
      following administration of 1-h and 4-h infusions of 2 g of meropenem every 8 h
      were 84.32% and 94.72%, respectively. These findings indicated that the V of
      meropenem was greater and the CL of meropenem was lower than the values obtained
      in a previous study with healthy subjects. The maximum recommended dose, i.e., 2
      g of meropenem every 8 h, may be required for treatment of life-threatening
      infections in this patient population. 

PMID- 25753629
TI  - Bactericidal efficiency and modes of action of the novel antimicrobial peptide
      T9W against Pseudomonas aeruginosa.
AB  - The antipseudomonal efficiency and mechanism of action of a novel engineered
      antimicrobial peptide, T9W, were evaluated in this study. T9W displayed high
      activity, with a lethal concentration (LC) of 1 to 4 MUM against Pseudomonas
      aeruginosa, including against ciprofloxacin-, gentamicin-, and ceftazidime
      resistant strains, even in the presence of 50 to 300 mM NaCl, 1 to 5 mM Ca(2+),
      or 0.5 to 2 mM Mg(2+). The time-kill curve (TKC) analysis demonstrated
      concentration-dependent activity, with T9W achieving complete killing in less
      than 30 min at 1* LC and in less than 5 min at 4* LC. Combination TKC analyses
      additionally demonstrated a synergistic effect with ciprofloxacin and gentamicin.
      The selectivity of T9W was further supported by its ability to specifically
      eliminate P. aeruginosa in a coculture with macrophages without toxicity to the
      mammalian cells. The results from fluorescent measurement indicated that T9W
      bound to lipopolysaccharide (LPS) and induced P. aeruginosa membrane
      depolarization, and microscopic observations and flow cytometry further indicated
      that T9W targeted the P. aeruginosa cell membrane and disrupted cytoplasmic
      membrane integrity, thereby causing cellular content release leading to cell
      death. This study revealed the potential usefulness of T9W as a novel
      antimicrobial agent against P. aeruginosa.

PMID- 25753630
TI  - Complete nucleotide sequences of bla(CTX-M)-harboring IncF plasmids from
      community-associated Escherichia coli strains in the United States.
AB  - Community-associated infections due to Escherichia coli producing CTX-M-type
      extended-spectrum beta-lactamases are increasingly recognized in the United
      States. The bla(CTX-M) genes are frequently carried on IncF group plasmids. In
      this study, bla(CTX-M-15)-harboring plasmids pCA14 (sequence type 131 [ST131])
      and pCA28 (ST44) and bla(CTX-M-14)-harboring plasmid pCA08 (ST131) were sequenced
      and characterized. The three plasmids were closely related to other IncFII
      plasmids from continents outside the United States in the conserved backbone
      region and multiresistance regions (MRRs). Each of the bla(CTX-M-15)-carrying
      plasmids pCA14 and pCA28 belonged to F31:A4:B1 (FAB [FII, FIA, FIB] formula) and
      showed a high level of similarity (92% coverage of pCA14 and 99% to 100%
      nucleotide identity), suggesting a possible common origin. The blaC(TX-M-14)
      carrying plasmid pCA08 belonged to F2:A2:B20 and was highly similar to pKF3-140
      from China (88% coverage of pCA08 and 99% to 100% nucleotide identity). All three
      plasmids carried multiple antimicrobial resistance genes and modules associated
      with virulence and biochemical pathways, which likely confer selective advantages
      for their host strains. The bla(CTX-M)-carrying IncFII-IA-IB plasmids implicated
      in community-associated infections in the United States shared key structural
      features with those identified from other continents, underscoring the global
      nature of this plasmid epidemic.

PMID- 25753631
TI  - Association between vancomycin day 1 exposure profile and outcomes among patients
      with methicillin-resistant Staphylococcus aureus infective endocarditis.
AB  - Given the critical importance of early appropriate therapy, a retrospective
      cohort (2002 to 2013) was performed at the Detroit Medical Center to evaluate the
      association between the day 1 vancomycin exposure profile and outcomes among
      patients with MRSA infective endocarditis (IE). The day 1 vancomycin area under
      the concentration-time curve (AUC0-24) and the minimum concentration at 24 h
      (Cmin 24) was estimated for each patient using the Bayesian procedure in ADAPT 5,
      an approach shown to accurately predict the vancomycin exposure with low bias and
      high precision with limited pharmacokinetic sampling. Initial MRSA isolates were
      collected and vancomycin MIC was determined by broth microdilution (BMD) and
      Etest. The primary outcome was failure, defined as persistent bacteremia (>=7
      days) or 30-day attributable mortality. Classification and regression tree
      analysis (CART) was used to determine the vancomycin exposure variables
      associated with an increased probability of failure. In total, 139 patients met
      study criteria; 76.3% had right-sided IE, 16.5% had left-sided IE, and 7.2% had
      both left and right-sided IE. A total of 89/139 (64%) experienced failure by
      composite definition. In the CART analysis, failure was more pronounced in
      patients with an AUC0-24/MIC as determined by BMD of <=600 relative to those with
      AUC0-24/MIC as determined by BMD of >600 (69.8% versus 54.7%, respectively, P =
      0.073). In the logistic regression analysis, an AUC/MIC as determined by BMD of
      <=600 (adjusted odds ratio, 2.3; 95% confidence interval, 1.01 to 5.37; P =
      0.047) was independently associated with failure. Given the retrospective nature
      of the present study, further prospective studies are required but these data
      suggest that patients with an AUC0-24/MIC as determined by BMD of <=600 present
      an increased risk of failure.

PMID- 25753632
TI  - Complete sequence of a bla(KPC)-harboring cointegrate plasmid isolated from
      Escherichia coli.
AB  - Horizontal transfer of bla(KPC)-harboring plasmids contributes significantly to
      the inter- and intraspecies spread of Klebsiella pneumoniae carbapenemase (KPC).
      Here we report the complete nucleotide sequence of a bla(KPC)-harboring IncFIA
      plasmid, pBK32533, from Escherichia coli. pBK32533 is a cointegrate plasmid
      comprising of a 72-kb sequence identical to that of the nonconjugative pBK30661
      plasmid plus an additional 170-kb element that harbors the genes for plasmid
      transfer. pBK32533 demonstrates how bla(KPC) can be spread from a nonconjugative
      plasmid through cointegration.

PMID- 25753633
TI  - Photochemotherapeutic strategy against Acanthamoeba infections.
AB  - Acanthamoeba is a protist pathogen that can cause serious human infections,
      including blinding keratitis and a granulomatous amoebic encephalitis that almost
      always results in death. The current treatment for these infections includes a
      mixture of drugs, and even then, a recurrence can occur. Photochemotherapy has
      shown promise in the treatment of Acanthamoeba infections; however, the selective
      targeting of pathogenic Acanthamoeba has remained a major concern. The mannose
      binding protein is an important adhesin expressed on the surface membranes of
      pathogenic Acanthamoeba organisms. To specifically target Acanthamoeba, the
      overall aim of this study was to synthesize a photosensitizing compound
      (porphyrin) conjugated with mannose and test its efficacy in vitro. The synthesis
      of mannose-conjugated porphyrin was achieved by mixing benzaldehyde and pyrrole,
      yielding tetraphenylporphyrin. Tetraphenylporphyrin was then converted into mono
      nitrophenylporphyrin by selectively nitrating the para position of the phenyl
      rings, as confirmed by nuclear magnetic resonance (NMR) spectroscopy. The mono
      nitrophenylporphyrin was reduced to mono-aminophenylporphyrin in the presence of
      tin dichloride and confirmed by a peak at m/z 629. Finally, mono-aminoporphyrin
      was conjugated with mannose, resulting in the formation of an imine bond. Mannose
      conjugated porphyrin was confirmed through spectroscopic analysis and showed that
      it absorbed light of wavelengths ranging from 425 to 475 nm. To determine the
      antiacanthamoebic effects of the derived product, amoebae were incubated with
      mannose-conjugated porphyrin for 1 h and washed 3 times to remove extracellular
      compound. Next, the amoebae were exposed to light of the appropriate wavelength
      for 1 h. The results revealed that mannose-conjugated porphyrin produced potent
      trophicidal effects and blocked excystation. In contrast, Acanthamoeba
      castellanii incubated with mannose alone and porphyrin alone did not exhibit an
      antiamoebic effect. Consistently, pretreatment with mannose-conjugated porphyrin
      reduced the A. castellanii-mediated host cell cytotoxicity from 97% to 4.9%. In
      contrast, treatment with porphyrin, mannose, or solvent alone had no protective
      effects on the host cells. These data suggest that mannose-conjugated porphyrin
      has application for the targeted photodynamic therapy of Acanthamoeba infections
      and may serve as a model in the development of therapeutic interventions against
      other eukaryotic infections.

PMID- 25753634
TI  - Risk factors for recurrence after successful treatment of Mycobacterium avium
      complex lung disease.
AB  - This study analyzed the recurrence rate and risk factors for recurrence of
      Mycobacterium avium complex (MAC) lung disease in patients successfully treated
      for this disease. The medical records of 158 patients successfully treated for
      MAC lung disease at a tertiary referral center in South Korea between March 2000
      and December 2009 were retrospectively analyzed. Recurrence was recorded, and
      factors associated with recurrence were analyzed. The mean age of the 158
      patients was 60.7 +/- 11.1 years. The etiologic agent was Mycobacterium avium in
      77 patients (48.7%) and Mycobacterium intracellulare in 81 patients (51.3%).
      Radiographic features included nodular bronchiectatic disease in 95 (60.1%),
      fibrocavitary disease in 49 (31.0%), and an unclassifiable form in 14 (8.9%)
      patients. Almost all (98.7%, 156/158) patients had been previously treated with a
      macrolide-containing regimen, and 68 (43.0%) patients had received treatment with
      an aminoglycoside. During a median follow-up of 43.8 months after completion of
      therapy, 50 patients (31.6%) experienced recurrence, at a median of 11.9 months
      after treatment completion. Multivariate analysis showed that only the nodular
      bronchiectatic form of the disease (hazard ratio, 2.39; 95% confidence interval,
      1.19 to 4.81) was independently associated with an increased risk of recurrence.
      Recurrence after successful treatment is frequent in patients with MAC lung
      disease. The recurrence rate was significantly higher in patients with the
      nodular bronchiectatic form than in those with the fibrocavitary form or an
      unclassifiable form of the disease. 

PMID- 25753635
TI  - In vitro activities of hexaazatrinaphthylenes against Leishmania spp.
AB  - The in vitro activity of a novel group of compounds, hexaazatrinaphthylene
      derivatives, against two species of Leishmania is described in this study. These
      compounds showed a significant dose-dependent inhibition effect on the
      proliferation of the parasites, with 50% inhibitory concentrations (IC(50)s)
      ranging from 1.23 to 25.05 MUM against the promastigote stage and 0.5 to 0.7 MUM
      against intracellular amastigotes. Also, a cytotoxicity assay was carried out to
      in order to evaluate the possible toxic effects of these compounds. Moreover,
      different assays were performed to determine the type of cell death induced after
      incubation with these compounds. The obtained results highlight the potential use
      of hexaazatrinaphthylene derivatives against Leishmania species, and further
      studies should be undertaken to establish them as novel leishmanicidal
      therapeutic agents.

PMID- 25753637
TI  - Ceftobiprole- and ceftaroline-resistant methicillin-resistant Staphylococcus
      aureus.
AB  - The role of mecA mutations in conferring resistance to ceftobiprole and
      ceftaroline, cephalosporins with anti-methicillin-resistant Staphylococcus aureus
      (MRSA) activity, was determined with MRSA strains COL and SF8300. The SF8300
      ceftaroline-passaged mutant carried a single mecA mutation, E447K (E-to-K change
      at position 447), and expressed low-level resistance. This mutation in COL
      conferred high-level resistance to ceftobiprole but only low-level resistance to
      ceftaroline. The COL ceftaroline-passaged mutant, which expressed high-level
      resistance to ceftobiprole and ceftaroline, had mutations in pbp2, pbp4, and gdpP
      but not mecA. 

PMID- 25753636
TI  - Pharmacodynamics of isavuconazole in an Aspergillus fumigatus mouse infection
      model.
AB  - Azole resistance is an emerging problem in Aspergillus fumigatus which translates
      into treatment failure. Alternative treatments with new azoles may improve
      therapeutic outcome in invasive aspergillosis (IA) even for strains with
      decreased susceptibility to current azoles. The in vivo efficacy of 0.25, 1, 4,
      16, 64, 128, 256, and 512 mg/kg of body weight/day prodrug isavuconazonium
      sulfate (BAL8557) (isavuconazole [ISA]-equivalent doses of 0.12, 0.48, 1.92,
      7.68, 30.7, 61.4, 122.9, and 245.8 mg/kg/day, respectively) administered by oral
      gavage was assessed in an immunocompetent murine model of IA against four
      clinical A. fumigatus isolates: a wild-type isolate (ISA MICEUCAST, 0.5 mg/liter)
      and three azole-resistant isolates harboring substitutions in the cyp51A gene:
      G54W (ISA MIC(EUCAST), 0.5 mg/liter), M220I (ISA MIC(EUCAST), 4 mg/liter), and
      TR34/L98H (ISA MIC(EUCAST), 8 mg/liter). The maximum effect (100% survival) was
      reached at a prodrug isavuconazonium sulfate dose of 64 mg/kg for the wild-type
      isolate, 128 mg/kg for the G54W mutant, and 256 mg/kg two times per day (q12) for
      the M220I mutant. A maximum response was not achieved with the TR34/L98H isolates
      with the highest dose of prodrug isavuconazonium sulfate (256 mg/kg q12). For a
      survival rate of 50%, the effective AUC(0-24)/MIC(EUCAST) ratio for ISA total
      drug was 24.73 (95% confidence interval, 22.50 to 27.18). The efficacy of
      isavuconazole depended on both the drug exposure and the isavuconazole MIC of the
      isolates. The quantitative relationship between exposure and effect (AUC(0
      24)/MIC) can be used to optimize the treatment of human infections by A.
      fumigatus, including strains with decreased susceptibility.

PMID- 25753638
TI  - Potential of novel antimicrobial peptide P3 from bovine erythrocytes and its
      analogs to disrupt bacterial membranes in vitro and display activity against drug
      resistant bacteria in a mouse model.
AB  - With the emergence of many antibiotic-resistant strains worldwide, antimicrobial
      peptides (AMPs) are being evaluated as promising alternatives to conventional
      antibiotics. P3, a novel hemoglobin peptide derived from bovine erythrocytes,
      exhibited modest antimicrobial activity in vitro. We evaluated the antimicrobial
      activities of P3 and an analog, JH-3, both in vitro and in vivo. The MICs of P3
      and JH-3 ranged from 3.125 MUg/ml to 50 MUg/ml when a wide spectrum of bacteria
      was tested, including multidrug-resistant strains. P3 killed bacteria within 30
      min by disrupting the bacterial cytoplasmic membrane and disturbing the
      intracellular calcium balance. Circular dichroism (CD) spectrometry showed that
      P3 assumed an alpha-helical conformation in bacterial lipid membranes, which was
      indispensable for antimicrobial activity. Importantly, the 50% lethal dose (LD50)
      of JH-3 was 180 mg/kg of mouse body weight after intraperitoneal (i.p.)
      injection, and no death was observed at any dose up to 240 mg/kg body weight
      following subcutaneous (s.c.) injection. Furthermore, JH-3 significantly
      decreased the bacterial count and rescued infected mice in a model of mouse
      bacteremia. In conclusion, P3 and an analog exhibited potent antimicrobial
      activities and relatively low toxicities in a mouse model, indicating that they
      may be useful for treating infections caused by drug-resistant bacteria. 

PMID- 25753639
TI  - beta-Lactams enhance daptomycin activity against vancomycin-resistant
      Enterococcus faecalis and Enterococcus faecium in in vitro
      pharmacokinetic/pharmacodynamic models.
AB  - Enterococcus faecalis and Enterococcus faecium are frequently resistant to
      vancomycin and beta-lactams. In enterococcal infections with reduced glycopeptide
      susceptibility, combination therapy is often administered. Our objective was to
      conduct pharmacokinetic/pharmacodynamic (PK/PD) models to evaluate beta-lactam
      synergy with daptomycin (DAP) against resistant enterococci. One E. faecalis
      strain (R6981) and two E. faecium strains (R6370 and 8019) were evaluated. DAP
      MICs were obtained. All strains were evaluated for response to LL37, an
      antimicrobial peptide, in the presence and absence of ceftaroline (CPT),
      ertapenem (ERT), and ampicillin (AMP). After 96 h, in vitro models were run
      simulating 10 mg DAP/kg body weight/day, 600 mg CPT every 8 h (q8h), 2 g AMP q4h,
      and 1 g ERT q24h, both alone and in combination against all strains. DAP MICs
      were 2, 4, and 4 MUg/ml for strains R6981, R6370, and 8019, respectively. PK/PD
      models demonstrated bactericidal activity with DAP-CPT, DAP-AMP, and DAP-ERT
      combinations against strain 8019 (P < 0.001 and log10 CFU/ml reduction of >2
      compared to any single agent). Against strains R6981 and R6370, the DAP-AMP
      combination demonstrated enhancement against R6370 but not R6981, while the
      combinations of DAP-CPT and DAP-ERT were bactericidal, demonstrated enhancement,
      and were statistically superior to all other regimens at 96 h (P < 0.001) against
      both strains. CPT, ERT, and AMP similarly augmented LL37 killing against strain
      8019. In strains R6981 and R6370, CPT and ERT aided LL37 more than AMP (P <
      0.001). Compared to DAP alone, combination regimens provide better killing and
      prevent resistance. Clinical research involving DAP combinations is warranted. 

PMID- 25753640
TI  - Influence of renal function estimation on pharmacokinetic modeling of vancomycin
      in elderly patients.
AB  - Vancomycin is a renally excreted drug, and its body clearance correlates with
      creatinine clearance. However, the renal function estimation equation that best
      predicts vancomycin clearance has not been established yet. The objective of this
      study was to compare the abilities of different renal function estimation
      equations to describe vancomycin pharmacokinetics in elderly patients. The NPAG
      algorithm was used to perform population pharmacokinetic analysis of vancomycin
      concentrations in 78 elderly patients. Six pharmacokinetic models of vancomycin
      clearance were built, based on the following equations: Cockcroft-Gault (CG),
      Jelliffe (JEL), Modification of Diet in Renal Disease (MDRD), Chronic Kidney
      Disease Epidemiology Collaboration (CKD-EPI) (both in milliliters per minute per
      1.73 m(2)), and modified MDRD and CKD-EPI equations (both in milliliters per
      minute). Goodness-of-fit and predictive performances of the six PK models were
      compared in a learning set (58 subjects) and a validation set (20 patients).
      Final analysis was performed to estimate population parameters in the entire
      population. In the learning step, the MDRD-based model best described the data,
      but the CG- and JEL-based models were the least biased. The mean weighted errors
      of prediction were significantly different between the six models (P = 0.0071).
      In the validation group, predictive performances were not significantly
      different. However, the use of a renal function estimation equation different
      from that used in the model building could significantly alter predictive
      performance. The final analysis showed important differences in parameter
      distributions and AUC estimation across the six models. This study shows that
      methods used to estimate renal function should not be considered interchangeable
      for pharmacokinetic modeling and model-based estimation of vancomycin
      concentrations in elderly patients.

PMID- 25753641
TI  - Antimicrobial and biophysical properties of surfactant supplemented with an
      antimicrobial peptide for treatment of bacterial pneumonia.
AB  - Antibiotic-resistant bacterial infections represent an emerging health concern in
      clinical settings, and a lack of novel developments in the pharmaceutical
      pipeline is creating a "perfect storm" for multidrug-resistant bacterial
      infections. Antimicrobial peptides (AMPs) have been suggested as future
      therapeutics for these drug-resistant bacteria, since they have potent broad
      spectrum activity, with little development of resistance. Due to the unique
      structure of the lung, bacterial pneumonia has the additional problem of
      delivering antimicrobials to the site of infection. One potential solution is
      coadministration of AMPs with exogenous surfactant, allowing for distribution of
      the peptides to distal airways and opening of collapsed lung regions. The
      objective of this study was to test various surfactant-AMP mixtures with regard
      to maintaining pulmonary surfactant biophysical properties and bactericidal
      functions. We compared the properties of four AMPs (CATH-1, CATH-2, CRAMP, and LL
      37) suspended in bovine lipid-extract surfactant (BLES) by assessing surfactant
      AMP mixture biophysical and antimicrobial functions. Antimicrobial activity was
      tested against methillicin-resistant Staphylococcus aureus and Pseudomonas
      aeruginosa. All AMP/surfactant mixtures exhibited an increase of spreading
      compared to a BLES control. BLES+CATH-2 mixtures had no significantly different
      minimum surface tension versus the BLES control. Compared to the other
      cathelicidins, CATH-2 retained the most bactericidal activity in the presence of
      BLES. The BLES+CATH-2 mixture appears to be an optimal surfactant-AMP mixture
      based on in vitro assays. Future directions involve investigating the potential
      of this mixture in animal models of bacterial pneumonia.

PMID- 25753642
TI  - A putative cro-like repressor contributes to arylomycin resistance in
      Staphylococcus aureus.
AB  - Antibiotic-resistant bacteria are a significant public health concern and
      motivate efforts to develop new classes of antibiotics. One such class of
      antibiotics is the arylomycins, which target type I signal peptidase (SPase), the
      enzyme responsible for the release of secreted proteins from their N-terminal
      leader sequences. Despite the essentiality, conservation, and relative
      accessibility of SPase, the activity of the arylomycins is limited against some
      bacteria, including the important human pathogen Staphylococcus aureus. To
      understand the origins of the limited activity against S. aureus, we
      characterized the susceptibility of a panel of strains to two arylomycin
      derivatives, arylomycin A-C16 and its more potent analog arylomycin M131. We
      observed a wide range of susceptibilities to the two arylomycins and found that
      resistant strains were sensitized by cotreatment with tunicamycin, which inhibits
      the first step of wall teichoic acid synthesis. To further understand how S.
      aureus responds to the arylomycins, we profiled the transcriptional response of
      S. aureus NCTC 8325 to growth-inhibitory concentrations of arylomycin M131 and
      found that it upregulates the cell wall stress stimulon (CWSS) and an operon
      consisting of a putative transcriptional regulator and three hypothetical
      proteins. Interestingly, we found that mutations in the putative transcriptional
      regulator are correlated with resistance, and selection for resistance ex vivo
      demonstrated that mutations in this gene are sufficient for resistance. The
      results begin to elucidate how S. aureus copes with secretion stress and how it
      evolves resistance to the inhibition of SPase.

PMID- 25753643
TI  - Efficacy of the investigational echinocandin ASP9726 in a guinea pig model of
      invasive pulmonary aspergillosis.
AB  - ASP9726 is an investigational echinocandin with in vitro activity against
      Aspergillus species. We evaluated the pharmacokinetics and efficacy of this agent
      in an established guinea pig model of invasive pulmonary aspergillosis. ASP9726
      plasma concentrations were measured in guinea pigs administered either a single
      dose or multiple doses of this agent at 2.5, 5, and 10 mg/kg of body weight/day
      by subcutaneous injection. Immunosuppressed guinea pigs were inoculated with A.
      fumigatus AF293, and ASP9726 (2.5, 5, and 10 mg/kg/day), voriconazole (10 mg/kg
      by oral gavage twice daily), or caspofungin (3 mg/kg/day by intraperitoneal
      injection) was administered for 8 days. Changes in fungal burden were measured by
      enumerating CFU and by quantitative PCR of specimens from within the lungs, as
      well as by analysis of serum (1 -> 3)-beta-D-glucan and galactomannan. Lung
      histopathology was also evaluated. ASP9726 plasma concentrations increased in a
      dose-proportional manner, and the drug was well tolerated at each dose. Each dose
      of ASP9726, voriconazole, and caspofungin significantly reduced pulmonary fungal
      burden as measured by quantitative PCR and by determining (1 -> 3)-beta-D-glucan
      and galactomannan levels, but only voriconazole significantly reduced numbers of
      CFU. ASP9726 at 5 mg/kg also significantly improved survival. Histopathology
      demonstrated morphological changes in hyphae in animals exposed to ASP9726 and
      caspofungin, consistent with the activities of the echinocandins. These results
      suggest that ASP9726 may be efficacious for the treatment of invasive pulmonary
      aspergillosis.

PMID- 25753644
TI  - Pharmacokinetics and pharmacodynamics of clofazimine in a mouse model of
      tuberculosis.
AB  - The antileprosy drug clofazimine has shown potential for shortening tuberculosis
      treatment; however, the current dosing of the drug is not evidence based, and the
      optimal dosing is unknown. Our objective was to conduct a preclinical evaluation
      of the pharmacokinetics and pharmacodynamics of clofazimine in the mouse model of
      tuberculosis, with the goal of providing useful information on dosing for future
      studies. Pharmacokinetic parameters were evaluated in infected and uninfected
      BALB/c mice. Pharmacodynamic parameters were evaluated in Mycobacterium
      tuberculosis-infected mice that were treated for 12 weeks with one of six
      different clofazimine dosing regimens, i.e., doses of 6.25, 12.5, and 25 mg/kg of
      body weight/day and 3 regimens with loading doses. Clofazimine progressively
      accumulated in the lungs, livers, and spleens of the mice, reaching levels of
      greater than 50 MUg/g in all tissues by 4 weeks of administration, while serum
      drug levels remained low at 1 to 2 MUg/ml. Elimination of clofazimine was
      extremely slow, and the half-life was dependent on the duration of drug
      administration. Clofazimine exhibited dose-dependent tissue and serum
      concentrations. At any dose, clofazimine did not have bactericidal activity
      during the first 2 weeks of administration but subsequently demonstrated potent,
      dose-independent bactericidal activity. The antituberculosis activity of
      clofazimine was dependent on neither the dose administered nor the drug
      concentrations in the tissues, suggesting that much lower doses could be
      effectively used for tuberculosis treatment.

PMID- 25753645
TI  - Fungal beta-1,3-glucan increases ofloxacin tolerance of Escherichia coli in a
      polymicrobial E. coli/Candida albicans biofilm.
AB  - In the past, biofilm-related research has focused mainly on axenic biofilms.
      However, in nature, biofilms are often composed of multiple species, and the
      resulting polymicrobial interactions influence industrially and clinically
      relevant outcomes such as performance and drug resistance. In this study, we show
      that Escherichia coli does not affect Candida albicans tolerance to amphotericin
      or caspofungin in an E. coli/C. albicans biofilm. In contrast, ofloxacin
      tolerance of E. coli is significantly increased in a polymicrobial E. coli/C.
      albicans biofilm compared to its tolerance in an axenic E. coli biofilm. The
      increased ofloxacin tolerance of E. coli is mainly biofilm specific, as ofloxacin
      tolerance of E. coli is less pronounced in polymicrobial E. coli/C. albicans
      planktonic cultures. Moreover, we found that ofloxacin tolerance of E. coli
      decreased significantly when E. coli/C. albicans biofilms were treated with
      matrix-degrading enzymes such as the beta-1,3-glucan-degrading enzyme lyticase.
      In line with a role for beta-1,3-glucan in mediating ofloxacin tolerance of E.
      coli in a biofilm, we found that ofloxacin tolerance of E. coli increased even
      more in E. coli/C. albicans biofilms consisting of a high-beta-1,3-glucan
      producing C. albicans mutant. In addition, exogenous addition of laminarin, a
      polysaccharide composed mainly of poly-beta-1,3-glucan, to an E. coli biofilm
      also resulted in increased ofloxacin tolerance. All these data indicate that beta
      1,3-glucan from C. albicans increases ofloxacin tolerance of E. coli in an E.
      coli/C. albicans biofilm.

PMID- 25753646
TI  - Activity of ceftazidime-avibactam against fluoroquinolone-resistant
      Enterobacteriaceae and Pseudomonas aeruginosa.
AB  - Ceftazidime-avibactam and comparator antibiotics were tested by the broth
      microdilution method against 200 Enterobacteriaceae and 25 Pseudomonas aeruginosa
      strains resistant to fluoroquinolones (including strains with the extended
      spectrum beta-lactamase [ESBL] phenotype and ceftazidime-resistant strains)
      collected from our institution. The MICs and mechanisms of resistance to
      fluoroquinolone were also studied. Ninety-nine percent of fluoroquinolone
      resistant Enterobacteriaceae strains were inhibited at a ceftazidime-avibactam
      MIC of <=4 mg/liter (using the susceptible CLSI breakpoint for ceftazidime alone
      as a reference). Ceftazidime-avibactam was very active against ESBL Escherichia
      coli (MIC90 of 0.25 mg/liter), ESBL Klebsiella pneumoniae (MIC90 of 0.5
      mg/liter), ceftazidime-resistant AmpC-producing species (MIC90 of 1 mg/liter),
      non-ESBL E. coli (MIC90 of <=0.125 mg/liter), non-ESBL K. pneumoniae (MIC90 of
      0.25 mg/liter), and ceftazidime-nonresistant AmpC-producing species (MIC90 of
      <=0.5 mg/liter). Ninety-six percent of fluoroquinolone-resistant P. aeruginosa
      strains were inhibited at a ceftazidime-avibactam MIC of <=8 mg/liter (using the
      susceptible CLSI breakpoint for ceftazidime alone as a reference), with a MIC90
      of 8 mg/liter. Additionally, fluoroquinolone-resistant mutants from each species
      tested were obtained in vitro from two strains, one susceptible to ceftazidime
      and the other a beta-lactamase producer with a high MIC against ceftazidime but
      susceptible to ceftazidime-avibactam. Thereby, the impact of fluoroquinolone
      resistance on the activity of ceftazidime-avibactam could be assessed. The MIC90
      values of ceftazidime-avibactam for the fluoroquinolone-resistant mutant strains
      of Enterobacteriaceae and P. aeruginosa were <=4 mg/liter and <=8 mg/liter,
      respectively. We conclude that the presence of fluoroquinolone resistance does
      not affect Enterobacteriaceae and P. aeruginosa susceptibility to ceftazidime
      avibactam; that is, there is no cross-resistance.

PMID- 25753647
TI  - Phrase Length and Prosody in On-Line Ambiguity Resolution.
AB  - We investigated the processing of ambiguous double-PP constructions in Hebrew.
      Selection restrictions forced the first prepositional phrase (PP1) to attach low,
      but PP2 could attach maximally high to VP or maximally low to the NP inside PP1.
      A length contrast in PP2 was also examined. This construction affords more
      potential locations for prosodic boundaries, and has a sharper structural
      contrast between the two attachment sites, than the single-PP construction which
      has yielded mixed results in previous work. A combined production-comprehension
      task showed more productions of pre-PP2 prosodic boundaries for long-PP2 than
      short-PP2. In comprehension, high PP2-attachment was favored by a prosodic
      boundary before PP2, regardless of PP2 length. This study provides performance
      data supporting the interplay of phrase lengths with structure-sensitivity as
      posited in the linguistics literature on the syntax-prosody interface, and
      supports the claim that readers are sensitive to the structural implications of
      the prosody they project onto sentences. 

PMID- 25753648
TI  - Improving red cell transfusion in the elective surgical setting: an improvement
      collaborative with evaluation.
AB  - BACKGROUND & OBJECTIVES: Significant research conducted in New South Wales (NSW)
      hospitals' indicated that about 30% of red cell transfusions in stable adult
      patients was inappropriate. Of the total Australian government blood product
      budget in 2009-2010 (i.e. $878.8 million dollars) was spent on fresh blood
      products and plasma collection. The Clinical Excellence Commission (CEC) launched
      a systematic intervention called Blood Watch (BW) aiming to reduce inappropriate
      red cell transfusions in all NSW hospitals. An evaluation of BW was undertaken to
      measure the effectiveness of the programme and to estimate the associated
      potential cost-saving. MATERIALS & METHODS: Through the deterministic linkage of
      the four population-based administrative databases, three outcome indicators and
      four process indicators were developed. The analyses were of five elective
      surgical groups as they were the focus of the interventions. Three-level logistic
      regression and three-level linear regression were used to explore the time trend
      of the study process and outcome indicators. Modelling of the possible avoided
      red cell transfusions was also undertaken using a quadratic regression technique.
      RESULTS: Overall, there was a 27.4% reduction of the blood usage after the
      introduction of the BW programme and the reductions were consistent across five
      elective surgical groups. Such a reduction was associated with annual cost
      savings of over $8.5 million. CONCLUSIONS: The BW programme which was based on
      collaborative improvement methods and implemented at scale led to significant
      reduction of blood usage, consistently across five elective surgical groups and
      significant cost-saving.

PMID- 25753649
TI  - Nodamura virus B2 amino terminal domain sensitivity to small interfering RNA.
AB  - Nodamura virus (NoV) B2, a suppressor of RNA interference, binds double stranded
      RNAs (dsRNAs) and small interfering RNAs (siRNAs) corresponding to Dicer
      substrates and products. Here, we report that the amino terminal domain of NoV B2
      (NoV B2 79) specifically binds siRNAs but not dsRNAs. NoV B2 79 oligomerizes on
      binding to 27 nucleotide siRNA. Mutation of the residues phenylalanine49 and
      alanine60 to cysteine and methionine, respectively enhances the RNA binding
      affinity of NoV B2 79. Circular dichroism spectra demonstrated that the wild type
      and mutant NoV B2 79 have similar secondary structure conformations. 

PMID- 25753650
TI  - Upregulation of lncRNA MEG3 Promotes Osteogenic Differentiation of Mesenchymal
      Stem Cells From Multiple Myeloma Patients By Targeting BMP4 Transcription.
AB  - Multiple myeloma (MM) is characterized by the impaired osteogenic differentiation
      of mesenchymal stromal cells (MSCs). However, the underlying molecular mechanisms
      are still poorly understood. Long noncoding RNAs (lncRNAs) are emerging as
      important regulatory molecules in tumor-suppressor and oncogenic pathways. Here
      we showed that MSCs from MM expressed less lncRNA MEG3 relative to those from
      normal donors during osteogenic differentiation. To evaluate the effect of MEG3
      on osteogenesis, bone marrow MSCs with enhanced or reduced MEG3 were prepared. We
      observed that MEG3 knockdown significantly reduced the expression of key
      osteogenic markers, including Runt-related transcription factor 2, osterix, and
      osteocalcin, while overexpression of MEG3 enhanced their expression.
      Additionally, MEG3 knockdown decreased BMP4 transcription. Here we showed that
      MEG3 was critical for SOX2 transcriptional repression of the BMP4. MEG3, which is
      located near the BMP4 gene, could dissociate the transcription factor SOX2 from
      the BMP4 promoter. A stable complex containing the MEG3, SOX2, and the SOX2
      consensus site of BMP4 suggested that MEG3 activated transcriptional activity by
      directly influencing SOX2 activity. By using assays such as luciferase, chromatin
      immunoprecipitation, and RNA immunoprecipitation, we showed that MEG3 had a
      critical function in a mechanism of promoter-specific transcriptional activation.
      These results suggested that MEG3 played an essential role in osteogenic
      differentiation in bone marrow MSCs, partly by activating BMP4 transcription. Our
      data provided novel evidence for the biological and clinical significance of
      lncRNA MEG3 expression as a potential biomarker for identifying patients with MM
      and as a potential therapeutic target in MM.

PMID- 25753651
TI  - Cenpj/CPAP regulates progenitor divisions and neuronal migration in the cerebral
      cortex downstream of Ascl1.
AB  - The proneural factor Ascl1 controls multiple steps of neurogenesis in the
      embryonic brain, including progenitor division and neuronal migration. Here we
      show that Cenpj, also known as CPAP, a microcephaly gene, is a transcriptional
      target of Ascl1 in the embryonic cerebral cortex. We have characterized the role
      of Cenpj during cortical development by in utero electroporation knockdown and
      found that silencing Cenpj in the ventricular zone disrupts centrosome biogenesis
      and randomizes the cleavage plane orientation of radial glia progenitors.
      Moreover, we show that downregulation of Cenpj in post-mitotic neurons increases
      stable microtubules and leads to slower neuronal migration, abnormal centrosome
      position and aberrant neuronal morphology. Moreover, rescue experiments shows
      that Cenpj mediates the role of Ascl1 in centrosome biogenesis in progenitor
      cells and in microtubule dynamics in migrating neurons. These data provide
      insights into genetic pathways controlling cortical development and primary
      microcephaly observed in humans with mutations in Cenpj. 

PMID- 25753653
TI  - Patient-satisfaction surveys on a scale of 0 to 10: improving health care, or
      leading it astray?
AB  - Patient-satisfaction surveys can call attention to the importance of treating
      patients with dignity and respect, but good ratings depend more on manipulable
      patient perceptions than on good medicine. In fact, the pressure to get good
      ratings can lead to bad medicine.

PMID- 25753654
TI  - OCT evaluation of directional atherectomy compared to balloon angioplasty.
AB  - Directional atherectomy (DA) is one of the most commonly used modalities for the
      treatment of obstructive femoropopliteal peripheral arterial disease (PAD),
      especially in patients with large and calcified atherosclerotic plaques. The
      effect of directional atherectomy to the vascular wall compared to balloon
      angioplasty by optical coherence tomography (OCT) has not been previously
      described. We present the first case of OCT after directional atherectomy with
      SilverHawk followed by angiosculpt balloon angioplasty. 

PMID- 25753652
TI  - Perceived discrimination and markers of cardiovascular risk among low-income
      African American youth.
AB  - OBJECTIVES: Our study examines the relationship between perceived discrimination
      and levels of C-reactive protein and blood pressure in low-income youth ages 10
      15 years old. METHODS: Data were collected from 10 to 15 year old focal children
      and their mothers. Face-to-face interviews were implemented to collect data on
      stressors including experiences of everyday discrimination from youth. High
      sensitivity CRP in dried blood spot samples and diastolic and systolic blood
      pressure were also collected at the time of the interview. RESULTS: Perceived
      discrimination among youth was significantly associated with higher levels of
      CRP, systolic, and diastolic blood pressure. CRP, systolic, and diastolic blood
      pressure remained significant after controlling for age-adjusted BMI, waist
      circumference, and other factors. CONCLUSIONS: Discrimination is a salient risk
      factor for inflammation and cardiovascular health. Early life course inflammation
      and cardiovascular reactivity are important candidate pathways through which the
      repeated exposure to discrimination for minority group members contributes to
      racial and economic health inequities in adulthood.

PMID- 25753655
TI  - The role of perceived need and health insurance in substance use treatment:
      implications for the Affordable Care Act.
AB  - The expansions in insurance coverage under the Patient Protection & Affordable
      Care Act (ACA) that took full effect in 2014 have been projected to increase the
      number of users of behavioral health services. By analyzing data from the 2008
      2012 National Survey on Drug Use and Health, this paper examines whether health
      insurance expansion may result in an increase in substance use disorder (SUD)
      treatment utilization. The study sample includes 18,600 adults with SUD but no
      diagnosable mental health condition. The analysis finds that over 80% of that
      population receives no treatment and 97% do not perceive a need for treatment.
      When they do receive treatment, they are more likely to receive mental health
      treatment. Using multinomial logistic regression, the study finds that having
      Medicaid or private insurance is associated with higher likelihood of receiving
      SUD treatment, but only when individuals perceive a need for it, compared to
      being uninsured and not perceiving a need for treatment (the reference category).
      These results indicate that increased service utilization is associated with
      perceiving a need for substance abuse treatment, implying that outreach
      initiatives to raise awareness about SUD and the effective role of substance use
      treatment are needed to enhance the impact of the structural changes to the
      substance abuse treatment system resulting from the ACA. 

PMID- 25753656
TI  - Prospective validation of predictive value of abdominal computed tomography scan
      on time to first treatment in Rai 0 chronic lymphocytic leukemia patients:
      results of the multicenter O-CLL1-GISL study.
AB  - OBJECTIVE: We performed an external and multicentric validation of the predictive
      value of abdominal computed tomography (aCT) on time to first treatment (TTFT) in
      early stage chronic lymphocytic leukemia (CLL) patients. METHODS: aCT was
      performed at diagnosis in 181 Rai 0 patients enrolled in the O-CLL1-GISL trial
      (clinicaltrial.gov ID:NCT00917549). RESULTS: Fifty-five patients showed an
      abnormal aCT. Patients with an abnormal aCT showed a significantly shorter TTFT
      than those with normal aCT (P < 0.0001). At multivariate analysis, aCT (P =
      0.011), beta-2 microglobulin (P = 0.019), and CD38 expression (P = 0.047)
      correlated with TTFT. Following IWCLL 2008 criteria, 112 (61.9%) cases remained
      at Rai 0, while 69 (38.1%) satisfied the criteria of clinical monoclonal B-cell
      lymphocytosis (cMBL). Reclassified Rai 0 patients with an abnormal aCT showed a
      significantly shorter TTFT than those with a normal aCT (P < 0.0001). At
      multivariate analysis, only aCT (P = 0.011) correlated with TTFT. Eleven cMBL
      cases (15.9%) showed an abnormal aCT and were reclassified as small lymphocytic
      lymphomas (SLL); nonetheless, TTFT was similar for cMBLs and SLLs. CONCLUSION:
      Our results confirm the ability of the abnormal aCT to predict progression in
      early stage cases.

PMID- 25753657
TI  - Electrodeposition of ZnO window layer for an all-atmospheric fabrication process
      of chalcogenide solar cell.
AB  - This paper presents the low cost electrodeposition of a transparent and
      conductive chlorine doped ZnO layer with performances comparable to that produced
      by standard vacuum processes. First, an in-depth study of the defect physics by
      ab-initio calculation shows that chlorine is one of the best candidates to dope
      the ZnO. This result is experimentally confirmed by a complete optical analysis
      of the ZnO layer deposited in a chloride rich solution. We demonstrate that high
      doping levels (>10(20) cm(-3)) and mobilities (up to 20 cm(2) V(-1) s(-1)) can be
      reached by insertion of chlorine in the lattice. The process developed in this
      study has been applied on a CdS/Cu(In,Ga)(Se,S)2 p-n junction produced in a pilot
      line by a non vacuum process, to be tested as solar cell front contact deposition
      method. As a result efficiency of 14.3% has been reached opening the way of
      atmospheric production of Cu(In,Ga)(Se,S)2 solar cell. 

PMID- 25753658
TI  - Large panel-survey data demonstrated country-level and ethnic minority variation
      in consent for health record linkage.
AB  - OBJECTIVES: To investigate individual, household, and country variation in
      consent to health record linkage. STUDY DESIGN AND SETTING: Data from 50,994
      individuals aged 16-74 years recruited to wave 1 of a large UK general purpose
      household survey (January 2009-December 2010) were analyzed using multilevel
      logistic regression models. RESULTS: Overall, 70.7% of respondents consented to
      record linkage. Younger age, marriage, tenure, car ownership, and education were
      all significantly associated with consent, although there was little deviation
      from 70% in subgroups defined by these variables. There were small increases in
      consent rates in individuals with poor health when defined by self-reported long
      term limiting illness [adjusted odds ratio (OR) = 1.11; 95% confidence intervals
      (CIs): 1.06, 1.16], less so when defined by General Health Questionnaire score
      (adjusted OR = 1.05; 95% CIs: 1.00, 1.10), but the range in absolute consent
      rates between categories was generally less than 10%. Larger differences were
      observed for those of nonwhite ethnicity who were 38% less likely to consent
      (adjusted OR = 0.62; 95% CIs: 0.59, 0.66). Consent was higher in Scotland than
      England (adjusted OR = 1.17; 95% CIs: 1.06, 1.29) but lower in Northern Ireland
      (adjusted OR = 0.56; 95% CIs: 0.50, 0.63). CONCLUSION: The modest overall level
      of systematic bias in consent to record linkage provides reassurance for record
      linkage potential in general purpose household surveys. However, the low consent
      rates among nonwhite ethnic minority survey respondents will further compound
      their low survey participation rates. The reason for the country-level variation
      requires further study.

PMID- 25753659
TI  - Hypoxia-induced gene expression results from selective mRNA partitioning to the
      endoplasmic reticulum.
AB  - Protein synthesis is a primary energy-consuming process in the cell. Therefore,
      under hypoxic conditions, rapid inhibition of global mRNA translation represents
      a major protective strategy to maintain energy metabolism. How some mRNAs,
      especially those that encode crucial survival factors, continue to be efficiently
      translated in hypoxia is not completely understood. By comparing specific
      transcript levels in ribonucleoprotein complexes, cytoplasmic polysomes and
      endoplasmic reticulum (ER)-bound ribosomes, we show that the synthesis of
      proteins encoded by hypoxia marker genes is favoured at the ER in hypoxia. Gene
      expression profiling revealed that transcripts particularly increased by the HIF
      1 transcription factor network show hypoxia-induced enrichment at the ER. We
      found that mRNAs favourably translated at the ER have higher conservation scores
      for both the 5'- and 3'-untranslated regions (UTRs) and contain less upstream
      initiation codons (uAUGs), indicating the significance of these sequence elements
      for sustained mRNA translation under hypoxic conditions. Furthermore, we found
      enrichment of specific cis-elements in mRNA 5'- as well as 3'-UTRs that mediate
      transcript localization to the ER in hypoxia. We conclude that transcriptome
      partitioning between the cytoplasm and the ER permits selective mRNA translation
      under conditions of energy shortage.

PMID- 25753660
TI  - Malleable nature of mRNA-protein compositional complementarity and its functional
      significance.
AB  - It has recently been demonstrated that nucleobase-density profiles of typical
      mRNA coding sequences exhibit a complementary relationship with nucleobase
      interaction propensity profiles of their cognate protein sequences. This finding
      supports the idea that the genetic code developed in response to direct binding
      interactions between amino acids and appropriate nucleobases, but also suggests
      that present-day mRNAs and their cognate proteins may be physicochemically
      complementary to each other and bind. Here, we computationally recode complete
      Methanocaldococcus jannaschii, Escherichia coli and Homo sapiens mRNA
      transcriptomes and analyze how much complementary matching of synonymous mRNAs
      can vary, while keeping protein sequences fixed. We show that for most proteins
      there exist cognate mRNAs that improve, but also significantly worsen the level
      of native matching (e.g. by 1.8 viz. 7.6 standard deviations on average for H.
      sapiens, respectively), with the least malleable proteins in this sense being
      strongly enriched in nuclear localization and DNA-binding functions. Even so, we
      show that the majority of recodings for most proteins result in pronounced
      complementarity. Our results suggest that the genetic code was designed for
      favorable, yet tunable compositional complementarity between mRNAs and their
      cognate proteins, supporting the hypothesis that the interactions between the two
      were an important defining element behind the code's origin.

PMID- 25753661
TI  - The ribonucleotidyl transferase USIP-1 acts with SART3 to promote U6 snRNA
      recycling.
AB  - The spliceosome is a large molecular machine that serves to remove the
      intervening sequences that are present in most eukaryotic pre-mRNAs. At its core
      are five small nuclear ribonucleoprotein complexes, the U1, U2, U4, U5 and U6
      snRNPs, which undergo dynamic rearrangements during splicing. Their reutilization
      for subsequent rounds of splicing requires reversion to their original
      configurations, but little is known about this process. Here, we show that
      ZK863.4/USIP-1 (U Six snRNA-Interacting Protein-1) is a ribonucleotidyl
      transferase that promotes accumulation of the Caenorhabditis elegans U6 snRNA.
      Endogenous USIP-1-U6 snRNA complexes lack the Lsm proteins that constitute the
      protein core of the U6 snRNP, but contain the U6 snRNP recycling factor
      SART3/B0035.12. Furthermore, co-immunoprecipitation experiments suggest that
      SART3 but not USIP-1 occurs also in a separate complex containing both the U4 and
      U6 snRNPs. Based on this evidence, genetic interaction between usip-1 and sart-3,
      and the apparent dissociation of Lsm proteins from the U6 snRNA during
      spliceosome activation, we propose that USIP-1 functions upstream of SART3 to
      promote U6 snRNA recycling.

PMID- 25753662
TI  - An intrinsically disordered region of methyl-CpG binding domain protein 2 (MBD2)
      recruits the histone deacetylase core of the NuRD complex.
AB  - The MBD2-NuRD (Nucleosome Remodeling and Deacetylase) complex is an epigenetic
      reader of DNA methylation that regulates genes involved in normal development and
      neoplastic diseases. To delineate the architecture and functional interactions of
      the MBD2-NuRD complex, we previously solved the structures of MBD2 bound to
      methylated DNA and a coiled-coil interaction between MBD2 and p66alpha that
      recruits the CHD4 nucleosome remodeling protein to the complex. The work
      presented here identifies novel structural and functional features of a
      previously uncharacterized domain of MBD2 (MBD2IDR). Biophysical analyses show
      that the MBD2IDR is an intrinsically disordered region (IDR). However, despite
      this inherent disorder, MBD2IDR increases the overall binding affinity of MBD2
      for methylated DNA. MBD2IDR also recruits the histone deacetylase core components
      (RbAp48, HDAC2 and MTA2) of NuRD through a critical contact region requiring two
      contiguous amino acid residues, Arg(286) and Leu(287). Mutating these residues
      abrogates interaction of MBD2 with the histone deacetylase core and impairs the
      ability of MBD2 to repress the methylated tumor suppressor gene PRSS8 in MDA-MB
      435 breast cancer cells. These findings expand our knowledge of the multi
      dimensional interactions of the MBD2-NuRD complex that govern its function.

PMID- 25753663
TI  - Structural insight into the mechanism of stabilization of the 7SK small nuclear
      RNA by LARP7.
AB  - The non-coding RNA 7SK is the scaffold for a small nuclear ribonucleoprotein
      (7SKsnRNP) which regulates the function of the positive transcription elongation
      factor P-TEFb in the control of RNA polymerase II elongation in metazoans. The La
      related protein LARP7 is a component of the 7SKsnRNP required for stability and
      function of the RNA. To address the function of LARP7 we determined the crystal
      structure of its La module, which binds a stretch of uridines at the 3'-end of
      7SK. The structure shows that the penultimate uridine is tethered by the two
      domains, the La-motif and the RNA-recognition motif (RRM1), and reveals that the
      RRM1 is significantly smaller and more exposed than in the La protein. Sequence
      analysis suggests that this impacts interaction with 7SK. Binding assays,
      footprinting and small-angle scattering experiments show that a second RRM domain
      located at the C-terminus binds the apical loop of the 3' hairpin of 7SK, while
      the N-terminal domains bind at its foot. Our results suggest that LARP7 uses both
      its N- and C-terminal domains to stabilize 7SK in a closed structure, which forms
      by joining conserved sequences at the 5'-end with the foot of the 3' hairpin and
      has thus functional implications.

PMID- 25753664
TI  - Insulin-response epigenetic activation of Egr-1 and JunB genes at the nuclear
      periphery by A-type lamin-associated pY19-Caveolin-2 in the inner nuclear
      membrane.
AB  - Insulin controls transcription to sustain its physiologic effects for the
      organism to adapt to environmental changes added to genetic predisposition.
      Nevertheless, insulin-induced transcriptional regulation by epigenetic factors
      and in defined nuclear territory remains elusive. Here we show that inner nuclear
      membrane (INM)-integrated caveolin-2 (Cav-2) regulates insulin-response
      epigenetic activation of Egr-1 and JunB genes at the nuclear periphery. INM
      targeted pY19-Cav-2 in response to insulin associates specifically with the A
      type lamin, disengages the repressed Egr-1 and JunB promoters from lamin A/C
      through disassembly of H3K9me3, and facilitates assembly of H3K9ac, H3K18ac and
      H3K27ac by recruitment of GCN5 and p300 and the subsequent enrichment of RNA
      polymerase II (Pol II) on the promoters at the nuclear periphery. Our findings
      show that Cav-2 is an epigenetic regulator of histone H3 modifications, and
      provide novel mechanisms of insulin-response epigenetic activation at the nuclear
      periphery.

PMID- 25753665
TI  - Stabilization of eukaryotic ribosomal termination complexes by deacylated tRNA.
AB  - Stabilization of the ribosomal complexes plays an important role in translational
      control. Mechanisms of ribosome stabilization have been studied in detail for
      initiation and elongation of eukaryotic translation, but almost nothing is known
      about stabilization of eukaryotic termination ribosomal complexes. Here, we
      present one of the mechanisms of fine-tuning of the translation termination
      process in eukaryotes. We show that certain deacylated tRNAs, remaining in the E
      site of the ribosome at the end of the elongation cycle, increase the stability
      of the termination and posttermination complexes. Moreover, only the part of eRF1
      recognizing the stop codon is stabilized in the A site of the ribosome, and the
      stabilization is not dependent on the hydrolysis of peptidyl-tRNA. The
      determinants, defining this property of the tRNA, reside in the acceptor stem. It
      was demonstrated by site-directed mutagenesis of tRNA(Val) and construction of a
      mini-helix structure identical to the acceptor stem of tRNA. The mechanism of
      this stabilization is different from the fixation of the unrotated state of the
      ribosome by CCA end of tRNA or by cycloheximide in the E site. Our data allow to
      reveal the possible functions of the isodecoder tRNAs in eukaryotes.

PMID- 25753666
TI  - Identification of metabolically stable 5'-phosphate analogs that support single
      stranded siRNA activity.
AB  - The ss-siRNA activity in vivo requires a metabolically stable 5'-phosphate
      analog. In this report we used crystal structure of the 5'-phosphate binding
      pocket of Ago-2 bound with guide strand to design and synthesize ss-siRNAs
      containing various 5'-phosphate analogs. Our results indicate that the electronic
      and spatial orientation of the 5'-phosphate analog was critical for ss-siRNA
      activity. Chemically modified ss-siRNA targeting human apoC III mRNA demonstrated
      good potency for inhibiting ApoC III mRNA and protein in transgenic mice.
      Moreover, ApoC III ss-siRNAs were able to reduce the triglyceride and LDL
      cholesterol in transgenic mice demonstrating pharmacological effect of ss-siRNA.
      Our study provides guidance to develop surrogate phosphate analog for ss-siRNA
      and demonstrates that ss-siRNA provides an alternative strategy for therapeutic
      gene silencing.

PMID- 25753667
TI  - Effects of DNA3'pp5'G capping on 3' end repair reactions and of an embedded
      pyrophosphate-linked guanylate on ribonucleotide surveillance.
AB  - When DNA breakage results in a 3'-PO4 terminus, the end is considered 'dirty'
      because it cannot prime repair synthesis by DNA polymerases or sealing by classic
      DNA ligases. The noncanonical ligase RtcB can guanylylate the DNA 3'-PO4 to form
      a DNA3'pp5'GOH cap. Here we show that DNA capping precludes end joining by
      classic ATP-dependent and NAD(+)-dependent DNA ligases, prevents template
      independent nucleotide addition by mammalian terminal transferase, blocks
      exonucleolytic proofreading by Escherichia coli DNA polymerase II and inhibits
      proofreading by E. coli DNA polymerase III, while permitting templated DNA
      synthesis from the cap guanosine 3'-OH primer by E. coli DNA polymerase II (B
      family) and E. coli DNA polymerase III (C family). Human DNA polymerase beta (X
      family) extends the cap primer predominantly by a single templated addition step.
      Cap-primed synthesis by templated polymerases embeds a pyrophosphate-linked
      ribonucleotide in DNA. We find that the embedded ppG is refractory to
      surveillance and incision by RNase H2.

PMID- 25753669
TI  - Fast and sensitive detection of indels induced by precise gene targeting.
AB  - The nuclease-based gene editing tools are rapidly transforming capabilities for
      altering the genome of cells and organisms with great precision and in high
      throughput studies. A major limitation in application of precise gene editing
      lies in lack of sensitive and fast methods to detect and characterize the induced
      DNA changes. Precise gene editing induces double-stranded DNA breaks that are
      repaired by error-prone non-homologous end joining leading to introduction of
      insertions and deletions (indels) at the target site. These indels are often
      small and difficult and laborious to detect by traditional methods. Here we
      present a method for fast, sensitive and simple indel detection that accurately
      defines indel sizes down to +/-1 bp. The method coined IDAA for Indel Detection
      by Amplicon Analysis is based on tri-primer amplicon labelling and DNA capillary
      electrophoresis detection, and IDAA is amenable for high throughput analysis. 

PMID- 25753668
TI  - Genome-wide CIITA-binding profile identifies sequence preferences that dictate
      function versus recruitment.
AB  - The class II transactivator (CIITA) is essential for the expression of major
      histocompatibility complex class II (MHC-II) genes; however, the role of CIITA in
      gene regulation outside of MHC-II biology is not fully understood. To
      comprehensively map CIITA-bound loci, ChIP-seq was performed in the human B
      lymphoblastoma cell line Raji. CIITA bound 480 sites, and was significantly
      enriched at active promoters and enhancers. The complexity of CIITA
      transcriptional regulation of target genes was analyzed using a combination of
      CIITA-null cells, including a novel cell line created using CRISPR/Cas9 tools.
      MHC-II genes and a few novel genes were regulated by CIITA; however, most other
      genes demonstrated either diminished or no changes in the absence of CIITA.
      Nearly all CIITA-bound sites were within regions containing accessible chromatin,
      and CIITA's presence at these sites was associated with increased histone H3K27
      acetylation, suggesting that CIITA's role at these non-regulated loci may be to
      poise the region for subsequent regulation. Computational genome-wide modeling of
      the CIITA bound XY box motifs provided constraints for sequences associated with
      CIITA-mediated gene regulation versus binding. These data therefore define the
      CIITA regulome in B cells and establish sequence specificities that predict
      activity for an essential regulator of the adaptive immune response.

PMID- 25753670
TI  - Short antisense-locked nucleic acids (all-LNAs) correct alternative splicing
      abnormalities in myotonic dystrophy.
AB  - Myotonic dystrophy type 1 (DM1) is an autosomal dominant multisystemic disorder
      caused by expansion of CTG triplet repeats in 3'-untranslated region of DMPK
      gene. The pathomechanism of DM1 is driven by accumulation of toxic transcripts
      containing expanded CUG repeats (CUG(exp)) in nuclear foci which sequester
      several factors regulating RNA metabolism, such as Muscleblind-like proteins
      (MBNLs). In this work, we utilized very short chemically modified antisense
      oligonucleotides composed exclusively of locked nucleic acids (all-LNAs)
      complementary to CUG repeats, as potential therapeutic agents against DM1. Our in
      vitro data demonstrated that very short, 8- or 10-unit all-LNAs effectively bound
      the CUG repeat RNA and prevented the formation of CUG(exp)/MBNL complexes. In
      proliferating DM1 cells as well as in skeletal muscles of DM1 mouse model the all
      LNAs induced the reduction of the number and size of CUG(exp) foci and corrected
      MBNL-sensitive alternative splicing defects with high efficacy and specificity.
      The all-LNAs had low impact on the cellular level of CUG(exp)-containing
      transcripts and did not affect the expression of other transcripts with short CUG
      repeats. Our data strongly indicate that short all-LNAs complementary to CUG
      repeats are a promising therapeutic tool against DM1.

PMID- 25753671
TI  - Development of a high-resolution NGS-based HLA-typing and analysis pipeline.
AB  - The human leukocyte antigen (HLA) complex contains the most polymorphic genes in
      the human genome. The classical HLA class I and II genes define the specificity
      of adaptive immune responses. Genetic variation at the HLA genes is associated
      with susceptibility to autoimmune and infectious diseases and plays a major role
      in transplantation medicine and immunology. Currently, the HLA genes are
      characterized using Sanger- or next-generation sequencing (NGS) of a limited
      amplicon repertoire or labeled oligonucleotides for allele-specific sequences.
      High-quality NGS-based methods are in proprietary use and not publicly available.
      Here, we introduce the first highly automated open-kit/open-source HLA-typing
      method for NGS. The method employs in-solution targeted capturing of the
      classical class I (HLA-A, HLA-B, HLA-C) and class II HLA genes (HLA-DRB1, HLA
      DQA1, HLA-DQB1, HLA-DPA1, HLA-DPB1). The calling algorithm allows for highly
      confident allele-calling to three-field resolution (cDNA nucleotide variants).
      The method was validated on 357 commercially available DNA samples with known HLA
      alleles obtained by classical typing. Our results showed on average an accurate
      allele call rate of 0.99 in a fully automated manner, identifying also errors in
      the reference data. Finally, our method provides the flexibility to add further
      enrichment target regions. 

PMID- 25753672
TI  - Dissecting the behavior and function of MBD3 in DNA methylation homeostasis by
      single-molecule spectroscopy and microscopy.
AB  - The detailed mechanism for DNA methylation homeostasis relies on an intricate
      regulatory network with a possible contribution from methyl-CpG-binding domain
      protein 3 (MBD3). In this study we examine the single-molecule behavior of MBD3
      and its functional implication in balancing the activity of DNA
      methyltransferases (DNMTs). Besides a localization tendency to DNA demethylating
      sites, MBD3 experiences a concurrent transcription with DNMTs in cell cycle.
      Fluorescence lifetime correlation spectroscopy (FLCS) and photon counting
      histogram (PCH) were applied to characterize the chromatin binding kinetics and
      stoichiometry of MBD3 in different cell phases. In the G1-phase, MBD3, in the
      context of the Mi-2/NuRD (nucleosome remodeling deacetylase) complex, could adopt
      a salt-dependent homodimeric association with its target epigenomic loci. Along
      with cell cycle progression, utilizing fluorescence lifetime imaging microscopy
      based Forster resonance energy transfer (FLIM-FRET) we revealed that a proportion
      of MBD3 and MBD2 would co-localize with DNMT1 during DNA maintenance methylation,
      providing a proofreading and protective mechanism against a possible excessive
      methylation by DNMT1. In accordance with our hypothesis, insufficient MBD3
      induced by small interfering RNA (siRNA) was found to result in a global DNA
      hypermethylation as well as increased methylation in the promoter CpG islands
      (CGIs) of a number of cell cycle related genes.

PMID- 25753673
TI  - A novel role for the mono-ADP-ribosyltransferase PARP14/ARTD8 in promoting
      homologous recombination and protecting against replication stress.
AB  - Genomic instability, a major hallmark of cancer cells, is caused by incorrect or
      ineffective DNA repair. Many DNA repair mechanisms cooperate in cells to fight
      DNA damage, and are generally regulated by post-translational modification of key
      factors. Poly-ADP-ribosylation, catalyzed by PARP1, is a post-translational
      modification playing a prominent role in DNA repair, but much less is known about
      mono-ADP-ribosylation. Here we report that mono-ADP-ribosylation plays an
      important role in homologous recombination DNA repair, a mechanism essential for
      replication fork stability and double strand break repair. We show that the mono
      ADP-ribosyltransferase PARP14 interacts with the DNA replication machinery
      component PCNA and promotes replication of DNA lesions and common fragile sites.
      PARP14 depletion results in reduced homologous recombination, persistent RAD51
      foci, hypersensitivity to DNA damaging agents and accumulation of DNA strand
      breaks. Our work uncovered PARP14 as a novel factor required for mitigating
      replication stress and promoting genomic stability.

PMID- 25753674
TI  - Involvement of ATM in homologous recombination after end resection and RAD51
      nucleofilament formation.
AB  - Ataxia-telangiectasia mutated (ATM) is needed for the initiation of the double
      strand break (DSB) repair by homologous recombination (HR). ATM triggers DSB end
      resection by stimulating the nucleolytic activity of CtIP and MRE11 to generate
      3'-ssDNA overhangs, followed by RPA loading and RAD51 nucleofilament formation.
      Here we show for the first time that ATM is also needed for later steps in HR
      after RAD51 nucleofilament formation. Inhibition of ATM after completion of end
      resection did not affect RAD51 nucleofilament formation, but resulted in HR
      deficiency as evidenced by (i) an increase in the number of residual
      RAD51/gammaH2AX foci in both S and G2 cells, (ii) the decrease in HR efficiency
      as detected by HR repair substrate (pGC), (iii) a reduced SCE rate and (iv) the
      radiosensitization of cells by PARP inhibition. This newly described role for ATM
      was found to be dispensable in heterochromatin-associated DSB repair, as KAP1
      depletion did not alleviate the HR-deficiency when ATM was inhibited after end
      resection. Moreover, we demonstrated that ATR can partly compensate for the
      deficiency in early, but not in later, steps of HR upon ATM inhibition. Taken
      together, we describe here for the first time that ATM is needed not only for the
      initiation but also for the completion of HR.

PMID- 25753675
TI  - Oxypurinol - A novel marker for wastewater contamination of the aquatic
      environment.
AB  - The anti-gout agent allopurinol is one of the most prescribed pharmaceuticals in
      Germany and is widely metabolized into oxypurinol (80%) as well as the
      corresponding riboside conjugates (10%) within the human body. To investigate the
      occurrence of allopurinol and oxypurinol in the urban water cycle an analytical
      method was developed based on solid phase extraction (SPE) and subsequent liquid
      chromatography electrospray-ionization tandem mass spectrometry (LC-MS/MS). In
      raw wastewater concentration levels of oxypurinol ranged up to 26.6 MUg L(-1),
      whereas allopurinol was not detected at all. In wastewater treatment plant (WWTP)
      effluents, concentrations of allopurinol were <LOQ, whereas oxypurinol
      concentrations ranged from 2.3 MUg L(-1) to 21.7 MUg L(-1). Elevated
      concentrations of oxypurinol in biologically treated wastewater originate from
      the transformation of allopurinol as well as the cleavage of allopurinol-9
      riboside, which was confirmed by laboratory experiments with activated sludge
      taken from a municipal WWTP. Further tracking of oxypurinol in the urban water
      cycle revealed its presence in rivers and streams (up to 22.6 MUg L(-1)),
      groundwater (up to 0.38 MUg L(-1)) as well as in finished drinking water (up to
      0.30 MUg L(-1)). Due to the high biological stability and the almost ubiquitous
      presence in the urban water cycle at elevated concentrations, oxypurinol might be
      used as marker for domestic wastewater in the environment. This was confirmed by
      correlation analysis to other wastewater markers with strong correlations of the
      concentrations of oxypurinol and carbamazepine (r(2) = 0.89) as well as of
      oxypurinol and primidone (r(2) = 0.82). 

PMID- 25753676
TI  - Identifying Haemophilus haemolyticus and Haemophilus influenzae by SYBR Green
      real-time PCR.
AB  - SYBR Green real time PCR assays for protein D (hpd), fuculose kinase (fucK) and
      [Cu, Zn]-superoxide dismutase (sodC) were designed for use in an algorithm for
      the identification of Haemophilus influenzae and H. haemolyticus. When tested on
      127 H. influenzae and 60 H. haemolyticus all isolates were identified correctly. 

PMID- 25753677
TI  - The mind, the lab, and the field: Three kinds of populations in scientific
      practice.
AB  - Scientists use models to understand the natural world, and it is important not to
      conflate model and nature. As an illustration, we distinguish three different
      kinds of populations in studies of ecology and evolution: theoretical,
      laboratory, and natural populations, exemplified by the work of R. A. Fisher,
      Thomas Park, and David Lack, respectively. Biologists are rightly concerned with
      all three types of populations. We examine the interplay between these different
      kinds of populations, and their pertinent models, in three examples: the notion
      of "effective" population size, the work of Thomas Park on Tribolium populations,
      and model-based clustering algorithms such as Structure. Finally, we discuss ways
      to move safely between three distinct population types while avoiding confusing
      models and reality. 

PMID- 25753678
TI  - Phosphahelicenes in asymmetric organocatalysis: [3+2] cyclizations of gamma
      substituted allenes and electron-poor olefins.
AB  - The first use of phosphahelicene in enantioselective organocatalysis is reported.
      New chiral phosphahelicenes have been prepared and enable highly enantioselective
      [3+2] cyclization reactions between arylidene- or alkylidenemalononitriles and
      gamma-substituted allenoates or cyanoallenes. These reactions afford cyclopentene
      derivatives in both high yields and diastereoselectivities, with enantiomeric
      excesses of up to 97 %. 

PMID- 25753679
TI  - Second opinion reporting in head and neck pathology: perspective on Mullin et al.

PMID- 25753680
TI  - Intimate partner violence and suicidal ideation in pregnant women.
AB  - Intimate partner violence (IPV) during pregnancy is a major public health issue
      with significant implications for maternal mental health. Less studied is the
      association between IPV during pregnancy and suicidal ideation. This study
      reports the prevalence and correlates of suicidal ideation among low-income
      pregnant women receiving prenatal care at a university obstetrical clinic from
      February 2009 to March 2010. We performed a cross-sectional analysis of 166 women
      surveyed between 24 and 28 weeks of gestation using the Edinburgh Postnatal
      Depression Scale (EPDS) and the Abuse Assessment Screen (AAS). Multiple logistic
      regression identified factors associated with antenatal suicidal ideation. The
      prevalence of suicidal ideation was 22.89 %. In the fully adjusted model,
      antenatal depressive symptomatology (OR = 17.04; 95 % CI 2.10-38.27) and
      experiencing IPV (OR = 9.37; 95 % CI 3.41-25.75) were significantly associated
      with an increased risk of antenatal suicidal ideation. The prevalence of
      antenatal suicidal ideation in the current study was higher than other population
      based samples though this sample was predominantly single, low-income, and 19 %
      experienced IPV during pregnancy. Given the strong association of antenatal
      suicidal ideation, depressive symptomatology, and IPV, health care providers are
      urged to identify those women at risk so that antenatal care can be tailored to
      best support optimal maternal and neonatal outcomes. 

PMID- 25753681
TI  - Electrocardiographic and electrophysiologic effects of dexmedetomidine on
      children.
AB  - BACKGROUND: Dexmedetomidine (DEX) is a highly selective alpha-2-adrenergic
      agonist approved for short-term sedation and monitored anesthesia care in adults.
      Its effects on the electrocardiography and cardiac conduction tissue are not well
      described in the literature. Therefore, we aimed to characterize the
      electrocardiographic and electrophysiologic effects of DEX in children. METHODS:
      Twenty children (11 boys and nine girls) between the ages of eight and 17
      undergoing electrophysiology study and ablation of the supraventricular
      tachycardia had hemodynamic and cardiac electrophysiologic variables measured
      before and during the administration of DEX (1 microgram/kg IV over 10 minutes
      followed by a 10-minute continuous infusion of 0.5 microgram/kg/h). RESULTS: A
      significant decrease in heart rate was seen after the administration of DEX, but
      the systolic-diastolic-mean arterial pressure, respiratory rate, and end-tidal
      carbon dioxide did not change. Corrected sinus node recovery times and baseline
      sinus cycle lengths, which are markers of sinus nodal function, were both
      lengthened with the administration of DEX. Atrioventricular (AV) nodal function,
      as evidenced by the Wenckebach cycle length, the ventriculoatrial block cycle
      length, and AV nodal effective refractory periods, was lengthened significantly.
      We also found that DEX increased the atrial refractory period and diminished
      atrial excitability. CONCLUSIONS: DEX significantly depressed sinus and AV nodal
      function in pediatric patients without significant electrocardiogram interval
      changes, other than a trend toward lower heart rates. Although no spontaneous AV
      nodal block and no clinically significant bradycardia were seen, we recommend
      that DEX be used with caution in patients at risk for bradycardia and/or AV nodal
      dysfunction due to its associated comorbidities.

PMID- 25753682
TI  - Multiple lichen planus-like keratoses: Lichenoid drug eruption simulant and under
      recognised cause of pruritic eruptions in the elderly.
AB  - We present six cases of multiple eruptive lichen planus-like keratoses (LPLK),
      occurring in older individuals predominately confined to previously solar exposed
      areas. Diagnosis was often confounded by the frequent histological reporting of
      'lichenoid drug reaction' (LDR), despite many of the patients being unmedicated.
      We review the literature regarding eruptive LPLK and reflect on their etiology,
      clinical aspects, management and importantly their clinicopathological
      differentiation from LDR. 

PMID- 25753683
TI  - Wide differences in mode of delivery within Europe: risk-stratified analyses of
      aggregated routine data from the Euro-Peristat study.
AB  - OBJECTIVE: To use data from routine sources to compare rates of obstetric
      intervention in Europe both overall and for subgroups at higher risk of
      intervention. DESIGN: Retrospective analysis of aggregated routine data. SETTING:
      Thirty-one European countries or regions contributing data on mode of delivery to
      the Euro-Peristat project. POPULATION: Births in participating countries in 2010.
      METHODS: Countries provided aggregated data about overall rates of obstetric
      intervention and about caesarean section rates for specified subgroups. MAIN
      OUTCOME MEASURES: Mode of delivery. RESULTS: Rates of caesarean section ranged
      from 14.8% to 52.2% of all births and rates of instrumental vaginal delivery
      ranged from 0.5% to 16.4%. Overall, there was no association between rates of
      instrumental vaginal delivery and rates of caesarean section, but similarities
      were observed between some countries that are geographically close and may share
      common traditions of practice. Associations were observed between caesarean
      section rates for women with breech and vertex births and with singleton and
      multiple births but patterns of association for women who had and had not had
      previous caesarean sections were more complex. CONCLUSIONS: The persisting wide
      variations in caesarean section and instrumental vaginal delivery rates point to
      a lack of consensus about practice and raise questions for further investigation.
      Further research is needed to explore the impact of differences in clinical
      guidelines, healthcare systems and their financing and parents' and
      professionals' attitudes to care at delivery.

PMID- 25753684
TI  - Fetal Growth and Neurodevelopmental Outcome in Congenital Heart Disease.
AB  - We evaluated differences in growth between fetuses with and without congenital
      heart disease (CHD) and tested associations between growth and early childhood
      neurodevelopment (ND). In this prospective cohort study, fetuses with hypoplastic
      left heart syndrome (HLHS), transposition of the great arteries (TGA), and
      tetralogy of Fallot (TOF) and controls had biparietal diameter (BPD), head (HC)
      and abdominal circumference (AC), femur length (FL), and estimated fetal weight
      (EFW) recorded serially during pregnancy at 18-26 weeks GA (F1), at 27-33 weeks
      GA (F2), and at 34-40 weeks GA (F3). CHD subjects underwent Bayley Scales of
      Infant Development-III ND testing at 18 months. Differences between CHD fetuses
      and controls were assessed using t tests and generalized linear modeling.
      Correlations between biometry and ND informed regression modeling. We enrolled 41
      controls and 68 fetuses with CHD (N = 24 HLHS, N = 21 TGA, N = 23 TOF), 46 of
      whom had ND scores available. At 18-26 weeks, CHD fetuses were smaller than
      controls in all biometric parameters. Differences in growth rates were observed
      for HC, BPD, and AC, but not for FL or EFW. Cognitive score correlated with HC/AC
      at F2 (r = -0.33, P = 0.04) and mean HC/AC across gestation (r = -0.35, P =
      0.03). Language correlated with FL/BPD at F2 (r = 0.34, P = 0.04). In stepwise
      linear regression, mean HC/AC predicted Cognition (B = -102, P = 0.026, R (2) =
      0.13) and FL/BPD at F2 predicted Language score (B = 127, P = 0.03, R (2) =
      0.12). Differences in growth between CHD fetuses and controls can be measured
      early in pregnancy. In CHD fetuses, larger abdominal relative to head
      circumference is associated with better 18-month neurodevelopment.

PMID- 25753685
TI  - Early Appearance of Principal Symptoms of Kawasaki Disease is a Risk Factor for
      Intravenous Immunoglobulin Resistance.
AB  - It is difficult to accurately predict treatment resistance in Kawasaki disease
      (KD). Patients considered to be low-risk cases often develop resistance to
      intravenous immunoglobulin (IVIG). We herein examined whether information from
      the clinical course of KD could improve the prediction accuracy of a previously
      reported risk score. We retrospectively reviewed the clinical records of 100 KD
      patients. The clinical characteristics and laboratory data were compared between
      IVIG-sensitive and IVIG-resistant patients and also between patients with and
      without coronary artery aneurysm (CAA). The total incidence of IVIG resistance
      and CAA development was 34 and 13 %, respectively. Multiple regression analysis
      identified the early appearance of principal symptoms (<=day 2 of the illness) as
      a risk factor for IVIG resistance (OR 2.88, 95 % CI 1.11-7.44, p = 0.0041),
      whereas delayed IVIG administration (>=day 6) (OR 2.23, 95 % CI 0.66-7.64, p =
      0.018) and IVIG resistance (OR 9.05, 95 % CI 2.27-36.10, p = 0.015) were
      independent predictors for CAA development. The addition of the first appearance
      day of principal symptoms into a previously reported scoring system improved its
      prediction accuracy for IVIG resistance. KD patients who had presented with any
      principal symptoms within 2 days of fever onset were at a high risk for IVIG
      resistance regardless of previously reported risk score. A careful medical
      history-taking that is focused on the clinical course enables a better prediction
      of IVIG resistance. 

PMID- 25753686
TI  - The Effects of Pulmonary Valve Replacement for Severe Pulmonary Regurgitation on
      Exercise Capacity and Cardiac Function.
AB  - Patients may develop hemodynamic abnormalities after right ventricular outflow
      tract (RVOT) repair. Re-intervention timing remains a dilemma. This study
      evaluates exercise capacity and RV function before and after intervention using
      age-related comparisons. Twenty-six patients with severe pulmonary regurgitation
      (PR) after initial repair scheduled for pulmonary valve replacement (PVR) were
      enrolled. Metabolic treadmill testing (EST) and MRI were obtained before and
      after surgery. EST results were compared with matched controls. Preoperative
      exercise time and peak oxygen consumption (VO2 max) were significantly diminished
      compared with controls but were not significantly different postoperatively. The
      patients were then split into age-related cohorts. When comparing pre-PVR and
      post-PVR exercise time and VO2 max among themselves, neither cohort showed
      significant differences. However, patients younger than 25 years had better
      postoperative results, an age-related difference not seen in the controls.
      Preoperative MRI showed significantly dilated RV, PR, and low normal function.
      After PVR, the right to left ventricular end-diastolic volume ratio (RVEDV:LVEDV)
      and pulmonary artery regurgitant fraction (RF) significantly decreased. There was
      no change in ventricular ejection fractions (EF). Severe PR, decreased RVEF, and
      RV dilation can significantly diminish exercise capacity. PVR improves
      RVEDV:LVEDV and RF, but not EF. Younger patients had better exercise capacity
      that was maintained postoperatively. This age-related difference was not seen in
      the controls, indicating that earlier intervention may preserve exercise
      capacity. Serial ESTs in patients with severe PR following RVOT repair may
      identify deteriorating exercise capacity as an early indicator for the need for
      PVR.

PMID- 25753687
TI  - Sphingolipids as cell fate regulators in lung development and disease.
AB  - Sphingolipids are a diverse class of signaling molecules implicated in many
      important aspects of cellular biology, including growth, differentiation,
      apoptosis, and autophagy. Autophagy and apoptosis are fundamental physiological
      processes essential for the maintenance of cellular and tissue homeostasis. There
      is great interest into the investigation of sphingolipids and their roles in
      regulating these key physiological processes as well as the manifestation of
      several disease states. With what is known to date, the entire scope of
      sphingolipid signaling is too broad, and a single review would hardly scratch the
      surface. Therefore, this review attempts to highlight the significance of
      sphingolipids in determining cell fate (e.g. apoptosis, autophagy, cell survival)
      in the context of the healthy lung, as well as various respiratory diseases
      including acute lung injury, acute respiratory distress syndrome,
      bronchopulmonary dysplasia, asthma, chronic obstructive pulmonary disease,
      emphysema, and cystic fibrosis. We present an overview of the latest findings
      related to sphingolipids and their metabolites, provide a short introduction to
      autophagy and apoptosis, and then briefly highlight the regulatory roles of
      sphingolipid metabolites in switching between cell survival and cell death.
      Finally, we describe functions of sphingolipids in autophagy and apoptosis in
      lung homeostasis, especially in the context of the aforementioned diseases. 

PMID- 25753688
TI  - Liposarcoma or invasive lipomatosis in flower horn fish, hybrid cichlid:
      clinical, radiological, ultrasonographical and histopathological study.
AB  - Liposarcoma or invasive lipomatosis affecting three indoor aquarium fish (flower
      horn fish, hybrid cichlid) is characterized, by the presence of mature adipocytes
      of variable sizes and by an invasive behaviour, which affected internal organs
      and eyes of all cases. Detailed macroscopic, radiological, ultrasonographical and
      histopathological features are presented. All fish had bilateral exophthalmia
      with some masses around the eyes. Ultrasonography confirmed the presence of
      hyperechoic masses in the eyes. Histopathology of all cases described the
      presence of variable-sized adipose cells in the eyes. The suggested diagnosis is
      well-differentiated liposarcoma or invasive lipomatosis. This is the first report
      of liposarcoma or invasive lipomatosis in flower horn fish, hybrid cichlid. 

PMID- 25753689
TI  - SIRT1 reduction causes renal and retinal injury in diabetes through endothelin 1
      and transforming growth factor beta1.
AB  - In diabetes, hyperglycaemia causes up-regulation of endothelin 1 (ET-1) and
      transforming growth factor beta 1 (TGF-beta1). Previously we showed glucose
      reduces sirtuin1 (SIRT1), a class III histone deacetylase. Here, we investigated
      the regulatory role of SIRT1 on ET-1 and TGF-beta1 expression. Human
      microvascular endothelial cells were examined following incubation with 25 mmol/l
      glucose (HG) and 5 mmol/l glucose (NG) with or without SIRT1 or histone acetylase
      p300 overexpression or knockdown. mRNA expressions of ET-1, TGF-beta1, SIRT1,
      p300 and collagen 1alpha(I) were examined. SIRT1 enzyme activity, ET-1 and TGF
      beta1 protein levels were measured. Histone acetylation and endothelial
      permeability were further investigated. Similar analyses were performed in the
      kidneys and retinas of SIRT1 overexpressing transgenic mice with or without
      streptozotocin induced diabetes. Renal functions were evaluated. In the
      endothelial cells (ECs), HG caused increased permeability and escalated
      production of ET-1, TGF-beta1, collagen Ialpha(I). These cells also showed
      increased p300 expression, histone acetylation and reduced SIRT1 levels. These
      changes were rectified in the ECs following p300 silencing or by SIRT1
      overexpression, whereas SIRT1 knockdown or p300 overexpression in NG mimicked the
      effects of HG. High ET-1 and TGF-beta1 levels were seen in the kidneys and
      retinas of diabetic mice along with micro-albuminuria and increased fibronectin
      protein (marker of glucose-induced cell injury) levels. Interestingly, these
      detrimental changes were blunted in SIRT1 overexpressing transgenic mice with
      diabetes. This study showed a novel SIRT1 mediated protection against renal and
      retinal injury in diabetes, regulated through p300, ET-1 and TGF-beta1.

PMID- 25753690
TI  - Development of Atrioventricular Block and Diagnostic Value of Stored Electrograms
      in Patients With Sick Sinus Syndrome and Implanted Pacemaker.
AB  - BACKGROUND: The incidence of atrioventricular block (AVB) in pacemaker patients
      with sick sinus syndrome (SSS) is not yet known. The aim of this study was to
      analyze AVB episodes in SafeR mode based on stored electrograms (EGM), and
      determine the occurrence rate and risk factors for advanced AVB in a pacemaker
      population with SSS. METHODS AND RESULTS: The study included 50 consecutive
      patients with SSS without a history of advanced AVB who had a dual-chamber
      pacemaker programmed in SafeR mode. A total of 377 EGM stored in the pacemakers
      as AVB episodes fulfilling the second- or third-degree criterion were analyzed.
      Of 377 EGM, 73 EGM (19.4%) were appropriate episodes, whereas the other EGM did
      not show actual AVB, and showed atrial tachyarrhythmia, ventricular event in the
      blanking period, or premature atrial contractions with block. On EGM analysis,
      advanced AVB occurred in 9 patients (18%), and the occurrence rate was 11.7% per
      year. Moreover, on multivariate analysis beta-blocker use was an independent risk
      factor for advanced AVB (OR, 9.10; P=0.004). CONCLUSIONS: The occurrence rate of
      advanced AVB in patients with SSS is much higher than previously reported, and
      beta-blocker use is an independent risk factor for advanced AVB. SafeR is useful
      to detect latent AVB. Stored EGM, however, sometimes include inaccurately
      classified events.

PMID- 25753691
TI  - Is high-dose catecholamine administration in small animals an appropriate model
      for takotsubo syndrome?

PMID- 25753692
TI  - Role of cardiac multidetector computed tomography beyond coronary angiography.
AB  - Cardiac multidetector computed tomography (MDCT) has become a useful noninvasive
      modality for anatomical imaging of coronary artery disease (CAD). Currently, the
      main clinical advantage of coronary computed tomography angiography (CCTA)
      appears to be related to its high negative predictive value at low or
      intermediate pretest probability for CAD. With the development of technical
      aspects of MDCT, clinical practice and research are increasingly shifting toward
      defining the clinical implication of plaque morphology, myocardial perfusion, and
      patient outcomes. The presence of positive vessel remodeling, low-attenuation
      plaques, napkin-ring sign, or spotty calcification on CCTA could be useful
      information on high-risk vulnerable plaques. The napkin-ring sign, especially,
      showed higher accuracy for the detection of thin-cap fibroatheroma. Recently, it
      was reported that cardiac 3D single-photon emission tomography/CT fusion imaging,
      noninvasive fractional flow reserve computed from CT, and integrated CCTA and CT
      myocardial perfusion were associated with improved diagnostic accuracy for the
      detection of hemodynamically significant CAD. Furthermore, several randomized,
      large clinical trials have evaluated the clinical value of CCTA for chest pain
      triage in the emergency department or long-term reduction in death, myocardial
      infarction, or hospitalization for unstable angina. In this review we discuss the
      role of cardiac MDCT beyond coronary angiography, including a comparison with
      other currently available imaging modalities used to examine atherosclerotic
      plaque and myocardial perfusion.

PMID- 25753693
TI  - Is high-dose catecholamine administration in small animals an appropriate model
      for takotsubo syndrome? - Reply.

PMID- 25753694
TI  - A feasibility study of a new computerised cognitive remediation for young adults
      with schizophrenia.
AB  - Cognitive remediation therapy is effective for improving cognition, symptoms and
      social functioning in individuals with schizophrenia; however, the impact on
      visual episodic memory remains unclear. The objectives of this feasibility study
      were: (1) to explore whether or not CIRCuiTS--a new computerised cognitive
      remediation therapy programme developed in England--improves visual episodic
      memory and other cognitive domains in young adults with early course
      schizophrenia; and (2) to evaluate acceptability of the CIRCuiTS programme in
      French-Canadians. Three participants with visual episodic memory impairments at
      baseline were recruited from clinical settings in Canada, and consented to
      participate. Neuropsychological, clinical and social functioning was evaluated at
      baseline and post-treatment. Intervention involved 40 sessions of cognitive
      remediation. First, the reliable change index (RCI) revealed that each
      participant demonstrated significant post-therapy change in episodic memory and
      in other cognitive domains. The response profile was characterised by the use of
      organisational strategies. Second, the treatment was considered acceptable to
      participants in terms of session frequency (number of sessions per week),
      intensity (hours per week; total hours), and number of missed sessions and total
      completed sessions. This preliminary study yielded encouraging data demonstrating
      the feasibility of the CIRCuiTS programme in French-Canadian young adults with
      schizophrenia.

PMID- 25753695
TI  - Sagittal plane coordination dynamics of typically developing gait.
AB  - BACKGROUND: Individuals who undergo an instrumented gait analysis often have an
      aberrant gait pattern due to neuromuscular impairments that adversely affect
      their coordination. Conventional instrumented gait analysis descriptors fail to
      capture the complex coordination dynamics of gait. This paper presents a
      straightforward methodology for generating descriptors of coordination dynamics
      based on dynamical systems theory and provides the largest reported dataset of
      sagittal plane coordination measures, including adjacent and non-adjacent segment
      pairings, from individuals free of gait pathology walking over-ground. METHODS:
      Tri-planar marker trajectories from 104 unimpaired subjects between the ages of 8
      and 66 years were collected as they walked at a self-selected speed on a level
      surface. Phase portraits for the pelvis, thigh, shank, and foot and continuous
      relative phase diagrams for the segment pairs of pelvis-thigh, thigh-shank, shank
      foot, and thigh-foot were calculated. FINDINGS: The low coefficients of variation
      for each coordination curve are comparable to inter-subject coefficients of
      variation for kinematic curves, narrow confidence intervals for relative phase
      angles at four essential footfall conditions, and small standard deviation bands
      of the continuous relative phase diagrams are evidence that these curves
      characterize the coordination dynamics of normal gait. INTERPRETATION: These
      findings support the use of this normative dataset as a reference for
      coordination studies in the clinic or research laboratory. Improving our
      understanding of gait strategies from the level of coordination and
      characterizing the natural variability in gait patterns offer a means to enhance
      our understanding of atypical gait patterns.

PMID- 25753696
TI  - Pathological changes in the subsynovial connective tissue increase with self
      reported carpal tunnel syndrome symptoms.
AB  - BACKGROUND: Fibrosis and thickening of the subysnovial connective tissue are the
      most common pathological findings in carpal tunnel syndrome. The relationship
      between subsynovial connective tissue characteristics and self-reported carpal
      tunnel syndrome symptoms was assessed. METHODS: Symptoms were characterized using
      the Boston Carpal Tunnel Questionnaire and Katz hand diagram in twenty-two
      participants (11 with symptoms, 11 with no symptoms). Using ultrasound, the
      thickness of the subsynovial connective tissue was measured using a thickness
      ratio (subsynovial thickness/tendon thickness) and gliding function was assessed
      using a shear strain index ((Displacement(tendon)
      Displacement(subsynovial))/Displacement(tendon)x 100). For gliding function,
      participants performed 10 repeated flexion-extension cycles of the middle finger
      at a rate of one cycle per second. FINDINGS: Participants with symptoms had a
      38.5% greater thickness ratio and 39.2% greater shear strain index compared to
      participants without symptoms (p<0.05). INTERPRETATION: Ultrasound detected
      differences the SSCT in symptomatic group that was characterized by low self
      reported symptom severity scores. This study found ultrasound useful for
      measuring structural and functional changes in the SSCT that could provide
      insight in the early pathophysiology associated with carpal tunnel syndrome
      symptoms.

PMID- 25753697
TI  - Estimation of the hip joint centre in human motion analysis: a systematic review.
AB  - BACKGROUND: Inaccuracies in locating the three-dimensional position of the hip
      joint centre affect the calculated hip and knee kinematics, force- and moment
      generating capacity of muscles and hip joint mechanics, which can lead to
      incorrect interpretations and recommendations in gait analysis. Several
      functional and predictive methods have been developed to estimate the hip joint
      centre location, and the International Society of Biomechanics recommends a
      functional approach for use with participants that have adequate range of motion
      at the hip, and predictive methods in those with insufficient range of motion.
      The purpose of the current systematic review was to substantiate the
      International Society of Biomechanics recommendations. This included identifying
      the most accurate functional and predictive methods, and defining 'adequate'
      range of motion. METHODS: A systematic search with broad search terms was
      performed including five databases. FINDINGS: The systematic search yielded to
      801 articles, of which 34 papers were included. Eleven different predictive and
      13 different functional methods were identified. The results showed that the
      geometric sphere fit method and Harrington equations are the most accurate
      functional and predictive approaches respectively that have been evaluated in
      vivo. INTERPRETATION: In regard to the International Society of Biomechanics
      recommendations, the geometric sphere fit method should be used in people with
      sufficient active hip range of motion and the Harrington equations should be used
      in patients without sufficient hip range of motion. Multi-plane movement trials
      with at least 60 degrees  of flexion-extension and 30 degrees  of ab-adduction
      range of motion are suggested when using functional methods.

PMID- 25753699
TI  - Annotation of glycomics MS and MS/MS spectra using the GlycoWorkbench software
      tool.
AB  - The GlycoWorkbench software tool allows users to semiautomatically annotate
      glycomics MS and MS/MS spectra and MS glycoproteomics spectra. The GlycanBuilder
      software tool is embedded within GlycoWorkbench allowing users to draw glycan
      structures and export images of the drawn structures. This chapter demonstrates
      to users how to draw glycan structures within GlycoWorkbench using the
      GlycanBuilder software tool. This chapter also demonstrates how to use
      GlycoWorkbench to import MS and MS/MS glycomics spectra and use the cascading
      annotation feature to annotate both the MS and MS/MS spectra with a single
      command. 

PMID- 25753698
TI  - Pharmacologic androgen deprivation and cardiovascular disease risk factors: a
      systematic review.
AB  - BACKGROUND: Pharmacologic androgen deprivation therapy (ADT) is widely used to
      treat prostate cancer. Observational studies suggest ADT is associated with
      cardiovascular disease and its risk factors; however, such studies may be subject
      to bias. Our objective was to evaluate the effect of ADT on cardiovascular
      disease risk factors using data from randomized controlled trials (RCTs).
      MATERIALS AND METHODS: We conducted a systematic review using MEDLINE and MEDLINE
      In-Process (1950-June 2013), EMBASE (1974-June 2013) and Web of Science (1900
      June 2013) for all RCTs in men with prostate cancer that compared pharmacologic
      ADT (i.e. use of gonadotropin-releasing hormone agonist or antagonist) with a
      group that did not receive ADT and reported data on cardiovascular disease risk
      factors including blood pressure, cholesterol, triglycerides, fibrinogen,
      biomarkers of insulin sensitivity, adiposity and C-reactive protein. We also
      searched for ongoing or unpublished trials. This study was registered at the
      PROSPERO International Prospective Register of Systematic Reviews
      (CRD42013005035). RESULTS: Of the 3272 unique publications identified in our
      systematic review, we did not identify a single RCT that reported data on any
      cardiovascular disease risk factor. We were unable to locate unreported data from
      corresponding authors or study sponsors. CONCLUSIONS: There is a lack of
      published, reliable evidence describing the effects of ADT on cardiovascular
      disease risk factors. RCTs have likely collected data on these risk factors as
      part of routine study monitoring; however, these data have not been published. To
      understand the effect of ADT on cardiovascular morbidity, these data must be made
      available to the scientific community.

PMID- 25753700
TI  - GlycoBase and autoGU: resources for interpreting HPLC-glycan data.
AB  - The biological relevance of protein glycosylation has made glycomics, the
      comprehensive study to identify all glycans in an organism, indispensable in many
      research fields. Determining the structure and functional relationship of
      glycoproteins requires the comprehensive characterization of glycan structures by
      a range of analytical methods. High performance liquid chromatography (HPLC) is a
      well-established technology commonly used for the complete structural elucidation
      of N- and O-linked glycans; however, the analysis of data is a major bottleneck
      and robust bioinformatic solutions are required. This chapter describes the
      availability of databases and tools, GlycoBase and autoGU developed in
      conjunction with the EUROCarbDB initiative, to assist the interpretation of HPLC
      glycan data collections. 

PMID- 25753701
TI  - NMR chemical shift prediction of glycans: application of the computer program
      CASPER in structural analysis.
AB  - Carbohydrate molecules have highly complex structures and the constituent
      monosaccharides and substituents are linked to each other in a large number of
      ways. NMR spectroscopy can be used to unravel these structures, but the process
      may be tedious and time-consuming. The computerized approach based on the CASPER
      program can facilitate rapid structural determination of glycans with little user
      intervention, which results in the most probable primary structure of the
      investigated carbohydrate material. Additionally, (1)H and (13)C NMR chemical
      shifts of a user-defined structure can be predicted, and this tool may thus be
      employed in many aspects where NMR spectroscopy plays an important part of a
      study. 

PMID- 25753702
TI  - Handling and conversion of carbohydrate sequence formats and monosaccharide
      notation.
AB  - Various glycobioinformatics resources have developed individual carbohydrate
      sequence formats to store and handle glycan data. This diversity of sequence
      formats is one of the major reasons for a rather low interoperability of
      glycobioinformatics resources. The formats have often been optimized to serve
      special requirements of the individual resources and are thus not fully
      compatible, but in many cases translation from one format to another is possible.
      This chapter summarizes some of the major glycan sequence formats and
      demonstrates the use of tools for translation between these formats. Some
      pitfalls that users of sequence conversion tools need to pay attention to are
      also illustrated. 

PMID- 25753703
TI  - Bacterial, plant, and fungal carbohydrate structure databases: daily usage.
AB  - Natural carbohydrates play important roles in living systems and therefore are
      used as diagnostic and therapeutic targets. The main goal of glycomics is
      systematization of carbohydrates and elucidation of their role in human health
      and disease. The amount of information on natural carbohydrates accumulates
      rapidly, but scientists still lack databases and computer-assisted tools needed
      for orientation in the glycomic information space. Therefore, freely available,
      regularly updated, and cross-linked databases are demanded. Bacterial
      Carbohydrate Structure Database (Bacterial CSDB) was developed for provision of
      structural, bibliographic, taxonomic, NMR spectroscopic, and other related
      information on bacterial and archaeal carbohydrate structures. Its main features
      are (1) coverage above 90%, (2) high data consistence (above 90% of error-free
      records), and (3) presence of manually verified bibliographic, NMR spectroscopic,
      and taxonomic annotations. Recently, CSDB has been expanded to cover
      carbohydrates of plant and fungal origin. The achievement of full coverage in the
      plant and fungal domains is expected in the future. CSDB is freely available on
      the Internet as a web service at http://csdb.glycoscience.ru. This chapter aims
      at showing how to use CSDB in your daily scientific practice.

PMID- 25753704
TI  - Using NMR data on GLYCOSCIENCES.de.
AB  - NMR spectroscopy is frequently used in structural characterization of
      carbohydrates. The GLYCOSCIENCES.de database contains more than 3,000 NMR spectra
      stored as lists of chemical shifts, which can be searched online by atom and
      residue names and by chemical shift values. This chapter describes how to use the
      different interfaces to get access to these data. The atom search allows querying
      the database for NMR spectra that contain a specific carbohydrate residue with an
      NMR shift in a given range assigned to a particular atom, whereas the peak search
      enables queries to find spectra with NMR shifts most similar to a list of given
      shifts. The shift estimation feature facilitates prediction of NMR shifts of
      glycans, for which no experimental data are available. 

PMID- 25753705
TI  - Glycomic analysis using KEGG GLYCAN.
AB  - This chapter describes the KEGG GLYCAN database of the KEGG resource, including
      descriptions of links to the other databases in KEGG. In particular, KEGG GLYCAN
      consists of glycan structures, with links to glycogenes, orthologs, reactions,
      pathways, drugs, diseases, and others, all within the KEGG resources. A number of
      analytical tools are also available, including the composite structure map (CSM),
      KegDraw, KCam, and GECS. These databases and tools will be described along with
      simple examples of their usage. 

PMID- 25753706
TI  - GlycomeDB.
AB  - Over the last two decades, several carbohydrate structure databases have been
      developed and made publicly available by different research groups around the
      world. This led to the fragmentation of information about carbohydrate structures
      into different resources that have no or only weak interaction with each other.
      GlycomeDB was developed to integrate the carbohydrate structures from different
      resources by generating a single-indexed catalog of these structures that
      associates each structure with its reference in the original resources. GlycomeDB
      facilitates searching for carbohydrate structures in all the integrated resources
      by eliminating the need to use several different search interfaces and manually
      integrating the results. References provided by GlycomeDB make it possible to
      retrieve information that is beyond the scope of GlycomeDB but present in the
      integrated databases. This chapter illustrates the use of the GlycomeDB search
      interfaces and web services by way of three example cases.

PMID- 25753707
TI  - Eukaryotic glycosylation: online methods for site prediction on protein
      sequences.
AB  - This chapter runs through several online predictors enabling prediction of
      glycosylation sites on protein sequences. Most online methods provide in place
      documentation and examples, but this chapter provides a general overview and
      workflow for each method. 

PMID- 25753708
TI  - Analyzing glycan structure synthesis with the Glycan Pathway Predictor (GPP)
      Tool.
AB  - This chapter describes the Glycan Pathway Predictor Tool, which is available as a
      part of the RINGS (Resource for INformatics of Glycomes at Soka) website at
      http://www.rings.t.soka.ac.jp/. It implements the mathematical model of N
      glycosylation previously described by Krambeck et al. (Glycobiology 19:1163-1175,
      2009). This tool computes the glycans that can be potentially generated from a
      select set of glyco-enzymes, based on a mathematical model that characterizes
      substrate specificity. The resulting glycans are displayed as a pathway map,
      which can be evaluated in an interactive manner. Detailed results can also be
      obtained for each glycan that is theoretically generated, along with the
      corresponding enzymes that were found to be involved with the selected glycan.
      Thus, glycobiologists can take a particular starting glycan structure as input,
      select a set of glyco-enzymes, and instantly retrieve the set of potentially
      synthesized glycans as a pathway map or as a text file. Applications of this tool
      are numerous, including prediction of glycan profiles for a glyco-gene knockout
      experiment, comparison with mass spectrometric data, etc.

PMID- 25753709
TI  - Functional network in posttranslational modifications: Glyco-Net in
      Glycoconjugate Data Bank.
AB  - Elucidating pathways related to posttranslational modifications (PTMs) such as
      glycosylation is of growing importance in post-genome science and technology.
      Graphical networks describing the relationships among glycan-related molecules,
      including genes, proteins, lipids, and various biological events, are considered
      extremely valuable and convenient tools for the systematic investigation of PTMs.
      Glyco-Net (http://bibi.sci.hokudai.ac.jp/functions/) can dynamically make network
      figures among various biological molecules and biological events. A certain
      molecule or event is expressed with a node, and the relationship between the
      molecule and the event is indicated by arrows in the network figures. In this
      chapter, we mention the features and current status of the Glyco-Net and a simple
      example of the search with the Glyco-Net.

PMID- 25753710
TI  - JCGGDB: Japan Consortium for Glycobiology and Glycotechnology Database.
AB  - The biological significance of glycans has been widely studied and reported in
      the past. However, most achievements of our predecessors are not readily
      available in existing databases. JCGGDB is a meta-database involving 15 original
      databases in AIST and 5 cooperative databases in alliance with JCGG: Japan
      Consortium for Glycobiology and Glycotechnology. It centers on a glycan structure
      database and accumulates information such as glycan preferences of lectins,
      glycosylation sites in proteins, and genes related to glycan syntheses from
      glycoscience and related fields. This chapter illustrates how to use three major
      search interfaces (Keyword Search, Structure Search, and GlycoChem Explorer)
      available in JCGGDB to search across multiple databases. 

PMID- 25753711
TI  - Glycan array data management at Consortium for Functional Glycomics.
AB  - Glycomics or the study of structure-function relationships of complex glycans has
      reshaped post-genomics biology. Glycans mediate fundamental biological functions
      via their specific interactions with a variety of proteins. Recognizing the
      importance of glycomics, large-scale research initiatives such as the Consortium
      for Functional Glycomics (CFG) were established to address these challenges. Over
      the past decade, the Consortium for Functional Glycomics (CFG) has generated
      novel reagents and technologies for glycomics analyses, which in turn have led to
      generation of diverse datasets. These datasets have contributed to understanding
      glycan diversity and structure-function relationships at molecular (glycan
      protein interactions), cellular (gene expression and glycan analysis), and whole
      organism (mouse phenotyping) levels. Among these analyses and datasets, screening
      of glycan-protein interactions on glycan array platforms has gained much
      prominence and has contributed to cross-disciplinary realization of the
      importance of glycomics in areas such as immunology, infectious diseases, cancer
      biomarkers, etc. This manuscript outlines methodologies for capturing data from
      glycan array experiments and online tools to access and visualize glycan array
      data implemented at the CFG. 

PMID- 25753712
TI  - Analyzing glycan-binding patterns with the ProfilePSTMM Tool.
AB  - This chapter describes the ProfilePSTMM Tool, which is available as a part of the
      RINGS (Resource for INformatics of Glycomes at Soka) website. It implements the
      probabilistic model previously described by Aoki-Kinoshita et al. (Bioinformatics
      22:e25-e34, 2006). This tool computes the glycan patterns that are found within a
      given set of glycan structures. Thus, one application of this tool is the
      extraction of monosaccharide patterns (profile) of a set of glycans that bind to
      a particular glycan-binding protein. Such patterns could be regarded as the
      monosaccharides that are important for glycan recognition. The resulting profiles
      are displayed similarly to Sequence Logos for amino acid motifs, where for each
      position in the glycan, the statistical distribution of monosaccharides that are
      found at that position are displayed graphically. An example of the analysis of
      Siglec-7 is described. 

PMID- 25753713
TI  - Exploring the specificities of glycan-binding proteins using glycan array data
      and the GlycoSearch software.
AB  - The glycan array is a powerful tool for investigating the specificities of glycan
      binding proteins. By incubating a glycan-binding protein on a glycan array, the
      relative binding to hundreds of different oligosaccharides can be quantified in
      parallel. Based on these data, much information can be obtained about the
      preference of a glycan-binding protein for specific subcomponents of
      oligosaccharides or motifs. In many cases, the analysis and interpretation of
      glycan array data can be time consuming and imprecise if done manually. Recently
      we developed software, called GlycoSearch, to facilitate the analysis and
      interpretation of glycan array data based on the previously developed methods
      called Motif Segregation and Outlier Motif Analysis. Here we describe the
      principles behind the software, the use of the software, and an example
      application. The automated, objective, and precise analysis of glycan array data
      should enhance the value of the data for a broad range of research applications. 

PMID- 25753714
TI  - Statistical analysis of amino acids in the vicinity of carbohydrate residues
      performed by GlyVicinity.
AB  - Protein-carbohydrate interactions are involved in various essential biological
      events. 3D structural data from the Protein Data Bank (PDB) can help to
      understand the molecular basis of the specificity of carbohydrate recognition by
      proteins. Such interactions can be analyzed statistically using GlyVicinity. This
      chapter exemplifies the usage of this tool to find information on the frequency
      of the occurrence of specific amino acids in the vicinity of individual
      carbohydrate residues and to analyze the type of interacting atoms and their
      spatial distribution around the glycans. 

PMID- 25753715
TI  - Tools to assist determination and validation of carbohydrate 3D structure data.
AB  - The frequency of glycosylated protein 3D structures in the Protein Data Bank
      (PDB) is significantly lower than the proportion of glycoproteins in nature, and
      if glycan 3D structures are present, then they often exhibit a large degree of
      errors. There are various reasons for this, one of which is a comparably low
      support of carbohydrates in software tools for 3D structure determination and
      validation. This chapter illustrates the current features that assist
      crystallographers with handling glycans during 3D structure determination in Coot
      and CNS and with validation of the results. 

PMID- 25753716
TI  - Glyco3D: a portal for structural glycosciences.
AB  - The present work describes, in a detailed way, a family of databases covering the
      three-dimensional features of monosaccharides, disaccharides, oligosaccharides,
      polysaccharides, glycosyltransferases, lectins, monoclonal antibodies against
      carbohydrates, and glycosaminoglycan-binding proteins. These databases have been
      developed with non-proprietary software, and they are open freely to the
      scientific community. They are accessible through the common portal called
      "Glyco3D" http://www.glyco3d.cermav.cnrs.fr. The databases are accompanied by a
      user-friendly graphical user interface (GUI) which offers several search options.
      All three-dimensional structures are available for visual consultations (with
      basic measurements possibilities) and can be downloaded in commonly used formats
      for further uses.

PMID- 25753717
TI  - Solution conformation of carbohydrates: a view by using NMR assisted by modeling.
AB  - Structural elucidation of complex carbohydrates in solution is not a trivial
      task. From the NMR view point, the limited chemical shift dispersion of sugar NMR
      spectra demands the combination of a variety of NMR techniques as well as the
      employment of molecular modeling methods. Herein, a general protocol for
      assignment of resonances and determination of inter-proton distances within the
      saccharides by homonuclear and heteronuclear experiments (i.e., (1)H and (13)C)
      is described. In addition, several computational tools and procedures for getting
      a final ensemble of geometries that represent the structure in solution are
      presented. 

PMID- 25753718
TI  - Informing saccharide structural NMR studies with density functional theory
      calculations.
AB  - Density functional theory (DFT) is a powerful computational tool to enable
      structural interpretations of NMR spin-spin coupling constants ( J-couplings) in
      saccharides, including the abundant (1)H-(1)H ( JHH), (13)C-(1)H ( JCH), and
      (13)C-(13)C ( JCC) values that exist for coupling pathways comprised of 1-4
      bonds. The multiple hydroxyl groups in saccharides, with their attendant lone
      pair orbitals, exert significant effects on J-couplings that can be difficult to
      decipher and quantify without input from theory. Oxygen substituent effects are
      configurational and conformational in origin (e.g., axial/equatorial orientation
      of an OH group in an aldopyranosyl ring; C-O bond conformation involving an
      exocyclic OH group). DFT studies shed light on these effects, and if conducted
      properly, yield quantitative relationships between a specific J-coupling and one
      or more conformational elements in the target molecule. These relationships
      assist studies of saccharide structure and conformation in solution, which are
      often challenged by the presence of conformational averaging. Redundant J
      couplings, defined as an ensemble of J-couplings sensitive to the same
      conformational element, are particularly helpful when the element is flexible in
      solution (i.e., samples multiple conformational states on the NMR time scale),
      provided that algorithms are available to convert redundant J-values into
      meaningful conformational models. If the latter conversion is achievable, the
      data can serve as a means of testing, validating, and refining theoretical
      methods like molecular dynamics (MD) simulations, which are currently relied upon
      heavily to assign conformational models of saccharides in solution despite a
      paucity of experimental data needed to independently validate the method.

PMID- 25753719
TI  - Energy maps for glycosidic linkage conformations.
AB  - Glycosidic linkage conformations are the main factors in determining the shapes
      of disaccharide, oligosaccharide, and polysaccharide molecules. The conformations
      are expressed in terms of the torsion angles about the bonds from each ring of
      the disaccharide moiety to its glycosidic oxygen atom, and the probability of a
      given conformation is often expressed in terms of its free or potential energy.
      The energy surface or map for a disaccharide is a display of the energy plotted
      against the two torsion angles. Successful mapping allows a particular kind of
      energy calculation to provide the energy values for each conformation and avoids
      possible pitfalls. Although different methods are discussed, the main emphasis of
      this chapter is on the technical production of the maps and their exploitation in
      further understanding the shape of the molecule in question. 

PMID- 25753720
TI  - Conformational analysis of oligosaccharides and polysaccharides using molecular
      dynamics simulations.
AB  - Complex carbohydrates usually have a large number of rotatable bonds and
      consequently a large number of theoretically possible conformations can be
      generated (combinatorial explosion). The application of systematic search methods
      for conformational analysis of carbohydrates is therefore limited to
      disaccharides and trisaccharides in a routine analysis. An alternative approach
      is to use Monte-Carlo methods or (high-temperature) molecular dynamics (MD)
      simulations to explore the conformational space of complex carbohydrates. This
      chapter describes how to use MD simulation data to perform a conformational
      analysis (conformational maps, hydrogen bonds) of oligosaccharides and how to
      build realistic 3D structures of large polysaccharides using Conformational
      Analysis Tools (CAT). 

PMID- 25753721
TI  - Molecular dynamics simulations of membrane- and protein-bound glycolipids using
      GLYCAM.
AB  - This chapter outlines protocols for the preparation, execution, and analysis of
      molecular dynamics (MD) simulations of glycolipids in biologically relevant
      environments, i.e., imbedded in lipid bilayers or bound to proteins, with the
      goal of generating biologically relevant structural and dynamic information. Also
      included is a description of ensemble average (EA) charge set development
      consistent with the GLYCAM06 force field and its implementation using the AMBER
      molecular dynamics software suite. 

PMID- 25753724
TI  - Calculating binding free energies for protein-carbohydrate complexes.
AB  - A variety of computational techniques may be applied to compute theoretical
      binding free energies for protein-carbohydrate complexes. Elucidation of the
      intermolecular interactions, as well as the thermodynamic effects, that
      contribute to the relative strength of receptor binding can shed light on
      biomolecular recognition, and the resulting initiation or inhibition of a
      biological process. Three types of free energy methods are discussed here,
      including MM-PB/GBSA, thermodynamic integration, and a non-equilibrium
      alternative utilizing SMD. Throughout this chapter, the well-known concanavalin A
      lectin is employed as a model system to demonstrate the application of these
      methods to the special case of carbohydrate binding. 

PMID- 25753722
TI  - Lipopolysaccharide membrane building and simulation.
AB  - While membrane simulations are widely employed to study the structure and
      dynamics of various lipid bilayers and membrane proteins in the bilayers,
      simulations of lipopolysaccharides (LPS) in membrane environments have been
      limited due to their structural complexity, difficulties in building LPS-membrane
      systems, and lack of the appropriate molecular force fields. In this work, as a
      first step to extend CHARMM-GUI Membrane Builder to incorporate LPS molecules and
      to explore their structures and dynamics in membrane environments using molecular
      dynamics simulations, we describe step-by-step procedures to build LPS bilayer
      systems using CHARMM and the recently developed CHARMM carbohydrate and lipid
      force fields. Such procedures are illustrated by building various bilayers of
      Escherichia coli R1.O6 LPS and the presentation of preliminary simulation results
      in terms of per-LPS area and density distributions of various components along
      the membrane normal. 

PMID- 25753723
TI  - Molecular dynamics simulations of glycoproteins using CHARMM.
AB  - Molecular dynamics simulations are an effective tool to study the structure,
      dynamics, and thermodynamics of carbohydrates and proteins. However, the
      simulations of heterogeneous glycoprotein systems have been limited due to the
      lack of appropriate molecular force field parameters describing the linkage
      between the carbohydrate and the protein regions as well as the tools to prepare
      these systems for modeling studies. In this work we outline the recent
      developments in the CHARMM carbohydrate force field to treat glycoproteins and
      describe in detail the step-by-step procedures involved in building glycoprotein
      geometries using CHARMM-GUI Glycan Reader. 

PMID- 25753725
TI  - Scoring functions for AutoDock.
AB  - Automated docking allows rapid screening of protein-ligand interactions. A
      scoring function composed of a force field and linear weights can be used to
      compute a binding energy from a docked atom configuration. For different force
      fields or types of molecules, it may be necessary to train a custom scoring
      function. This chapter describes the data and methods one must consider in
      developing a custom scoring function for use with AutoDock. 

PMID- 25753726
TI  - Structures of glycans bound to receptors from saturation transfer difference
      (STD) NMR spectroscopy: quantitative analysis by using CORCEMA-ST.
AB  - Glycan-receptor interactions are of fundamental relevance for a large number of
      biological processes, and their kinetics properties (medium/weak binding
      affinities) make them appropriated to be studied by ligand observed NMR
      techniques, among which saturation transfer difference (STD) NMR spectroscopy has
      been shown to be a very robust and powerful approach. The quantitative analysis
      of the results from a STD NMR study of a glycan-receptor interaction is essential
      to be able to translate the resulting spectral intensities into a 3D molecular
      model of the complex. This chapter describes how to carry out such a quantitative
      analysis by means of the Complete Relaxation and Conformational Exchange Matrix
      Approach for STD NMR (CORCEMA-ST), in general terms, and an example of a previous
      work on an antibody-glycan interaction is also shown. 

PMID- 25753727
TI  - QM/MM methods for studying enzymatic reactions of glycosyltransferases.
AB  - Hybrid quantum mechanics and molecular mechanics (QM/MM) methods have become a
      powerful tool to provide an accurate and effective description of complex
      biological systems. The QM treatment of the electronic structure of an active
      site region and the rest of the enzyme by molecular mechanics allows enzymatic
      reaction to being modeled with including the impact of environment. Different
      reaction pathways of the enzymatic mechanism can be tested--transition states
      (TS) and intermediates characterized using QM/MM methods, leading to significant
      advances in understanding enzymatic reactions. This chapter discusses the ideas
      and the setting up of the structural and computational models for calculations
      with QM/MM software. The use of QM/MM methodology is also illustrated using the
      case of the inverting glycosyltransferase GnT-I.

PMID- 25753728
TI  - Recommendations for postpartum hemorrhage in women who decline blood transfusion.

PMID- 25753729
TI  - Rescue of Methyl-CpG Binding Protein 2 Dysfunction-induced Defects in Newborn
      Neurons by Pentobarbital.
AB  - Rett syndrome is a neurodevelopmental disorder that usually arises from mutations
      or deletions in methyl-CpG binding protein 2 (MeCP2), a transcriptional regulator
      that affects neuronal development and maturation without causing cell loss. Here,
      we show that silencing of MeCP2 decreased neurite arborization and synaptogenesis
      in cultured hippocampal neurons from rat fetal brains. These structural defects
      were associated with alterations in synaptic transmission and neural network
      activity. Similar retardation of dendritic growth was also observed in MeCP2
      deficient newborn granule cells in the dentate gyrus of adult mouse brains in
      vivo, demonstrating direct and cell-autonomous effects on individual neurons.
      These defects, caused by MeCP2 deficiency, were reversed by treatment with the US
      Food and Drug Administration-approved drug, pentobarbital, in vitro and in vivo,
      possibly caused by modulation of gamma-aminobutyric acid signaling. The results
      indicate that drugs modulating gamma-aminobutyric acid signaling are potential
      therapeutics for Rett syndrome.

PMID- 25753730
TI  - RNA-targeted Therapeutics for ALS.
AB  - Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease leading to
      cell death of predominantly motor neurons. Despite extensive research in this
      disease, finding a way to slow the progress of the disease has been challenging.
      RNA-targeted therapeutic approaches, including small interfering RNA and
      antisense oligonucleotides are being developed for genetic forms of ALS. ALS
      provides an unique opportunity for the use of RNA inhibition strategies given a
      well-defined animal model, extensive available information regarding the
      causative genes, and recent experience in phase 1 clinical trial. 

PMID- 25753732
TI  - The orphan GPCR, Gpr161, regulates the retinoic acid and canonical Wnt pathways
      during neurulation.
AB  - The vacuolated lens (vl) mouse mutation arose on the C3H/HeSnJ background and
      results in lethality, neural tube defects (NTDs) and cataracts. The vl phenotypes
      are due to a deletion/frameshift mutation in the orphan GPCR, Gpr161. A recent
      study using a null allele demonstrated that Gpr161 functions in primary cilia and
      represses the Shh pathway. We show the hypomorphic Gpr161(vl) allele does not
      severely affect the Shh pathway. To identify additional pathways regulated by
      Gpr161 during neurulation, we took advantage of naturally occurring genetic
      variation in the mouse. Previously Gpr161(vl-C3H) was crossed to different inbred
      backgrounds including MOLF/EiJ and the Gpr161(vl) mutant phenotypes were rescued.
      Five modifiers were mapped (Modvl: Modifier of vl) including Modvl5(MOLF). In
      this study we demonstrate the Modvl5(MOLF) congenic rescues the Gpr161(vl)
      associated lethality and NTDs but not cataracts. Bioinformatics determined the
      transcription factor, Cdx1, is the only annotated gene within the Modvl5 95% CI
      co-expressed with Gpr161 during neurulation and not expressed in the eye. Using
      Cdx1 as an entry point, we identified the retinoid acid (RA) and canonical Wnt
      pathways as downstream targets of Gpr161. QRT-PCR, ISH and IHC determined that
      expression of RA and Wnt genes are down-regulated in Gpr161(vl/vl) but rescued by
      the Modvl5(MOLF) congenic during neurulation. Intraperitoneal RA injection
      restores expression of canonical Wnt markers and rescues Gpr161(vl/vl) NTDs.
      These results establish the RA and canonical Wnt as pathways downstream of Gpr161
      during neurulation, and suggest that Modvl5(MOLF) bypasses the Gpr161(vl)
      mutation by restoring the activity of these pathways. 

PMID- 25753731
TI  - Novel In Vivo model for combinatorial fluorescence labeling in mouse prostate.
AB  - BACKGROUND: The epithelial layer of prostate glands contains several types of
      cells, including luminal and basal cells. Yet there is paucity of animal models
      to study the cellular origin of normal or neoplastic development in the prostate
      to facilitate the treatment of heterogenous prostate diseases by targeting
      individual cell lineages. METHODS: We developed a mouse model that expresses
      different types of fluorescent proteins (XFPs) specifically in prostatic cells.
      Using an in vivo stochastic fluorescent protein combinatorial strategy, XFP
      signals were expressed specifically in prostate of Protein Kinase D1 (PKD1) knock
      out, K-Ras(G) (12) (D) knock-in, and Phosphatase and tensin homolog (PTEN) and
      PKD1 double knock-out mice under the control of PB-Cre promoter. RESULTS: In vivo
      XFP signals were observed in prostate of PKD1 knock-out, K-Ras(G) (12) (D) knock
      in, and PTEN PKD1 double knock-out mice, which developed normal, hyperplastic,
      and neoplastic prostate, respectively. The patchy expression pattern of XFPs in
      neoplasia tissue indicated the clonal origin of cancer cells in the prostate.
      CONCLUSIONS: The transgenic mouse models demonstrate combinatorial fluorescent
      protein expression in normal and cancerous prostatic tissues. This novel prostate
      specific fluorescent labeled mouse model, which we named Prorainbow, could be
      useful in studying benign and malignant pathology of prostate.

PMID- 25753734
TI  - Low-dose administration of oral pazopanib for the treatment of recurrent
      angiosarcoma.

PMID- 25753735
TI  - Microhabitat use affects goby (Gobiidae) cue choice in spatial learning task.
AB  - This study investigated whether spatial learning ability and cue use of gobies
      (Gobiidae) from two contrasting habitats differed in a spatial task. Gobies were
      collected from the spatially complex rock pools and dynamic, homogenous sandy
      shores. Fishes were trained to locate a shelter under the simulated threat of
      predation and it was determined whether they used local or extra-maze (global)
      and geometric cues to do so. It was hypothesized that fishes from rock pools
      would outperform fishes from sandy shores in their ability to relocate shelter
      and the two groups would differ in their cue use. It was found that rock-pool
      species learnt the location of the correct shelter much faster, made fewer errors
      and used a combination of all available cues to locate the shelter, while sand
      species relied significantly more on extra-maze and geometric cues for
      orientation. The results reported here support the hypothesis that fishes living
      in complex habitats have enhanced capacity for spatial learning and are more
      likely to rely on local landmarks as directional cues than fishes living in
      mundane habitats where local cues such as visual landmarks are unreliable. 

PMID- 25753733
TI  - The dynamics of plus end polarization and microtubule assembly during Xenopus
      cortical rotation.
AB  - The self-organization of dorsally-directed microtubules during cortical rotation
      in the Xenopus egg is essential for dorsal axis formation. The mechanisms
      controlling this process have been problematic to analyze, owing to difficulties
      in visualizing microtubules in living egg. Also, the order of events occurring at
      the onset of cortical rotation have not been satisfactorily visualized in vivo
      and have been inferred from staged fixed samples. To address these issues, we
      have characterized the dynamics of total microtubule and plus end behavior
      continuously throughout cortical rotation, as well as in oocytes and unfertilized
      eggs. Here, we show that the nascent microtubule network forms in the cortex but
      associates with the deep cytoplasm at the start of rotation. Importantly, plus
      ends remain cortical and become increasingly more numerous and active prior to
      rotation, with dorsal polarization occurring rapidly after the onset of rotation.
      Additionally, we show that vegetally localized Trim36 is required to attenuate
      dynamic plus end growth, suggesting that vegetal factors are needed to locally
      coordinate growth in the cortex. 

PMID- 25753736
TI  - Nurses experience of using scientific knowledge in clinical practice: a grounded
      theory study.
AB  - BACKGROUND: Guidelines recommend the use of evidence-based practice in nursing.
      Nurses are expected to give patients care and treatment based on the best
      knowledge available. They may have knowledge and positive attitudes, but this
      does not mean that they are basing their work on evidence-based practice.
      Knowledge is still lacking about what is needed to successfully implement
      evidence-based practice. AIM: The aim of this study was to gain more knowledge
      about what nurses perceive as the most important challenge in implementing
      evidence-based practice and to explain how they act to face and overcome this
      challenge. METHOD: We used classical grounded theory methodology and collected
      data through four focus groups and one individual interview in different
      geographical locations in one large hospital trust in Norway. Fourteen registered
      clinical practice nurses participated. We analysed the data in accordance with
      grounded theory, using the constant comparative method. RESULTS: Contextual
      balancing of knowledge emerged as the core category and explains how the nurses
      dealt with their main concern, how to determine what types of knowledge they
      could trust. The nurses' main strategies were an inquiring approach, examining
      knowledge and maintaining control while taking care of patients. They combined
      their own experienced-based knowledge and the guidelines of evidence-based
      practice with a sense of control in the actual situation. CONCLUSION: The
      grounded theory contextual balancing of knowledge may help us to understand how
      nurses detect what types of knowledge they can trust in clinical practice. The
      nurses needed to rely on what they did, and they seemed to rely on their own
      experience rather than on research.

PMID- 25753737
TI  - Targeted next-generation sequencing reveals novel EYS mutations in Chinese
      families with autosomal recessive retinitis pigmentosa.
AB  - EYS mutations demonstrate great genotypic and phenotypic varieties, and are one
      of the major causes for patients with autosomal recessive retinitis pigmentosa
      (ARRP). Here, we aim to determine the genetic lesions with phenotypic
      correlations in two Chinese families with ARRP. Medical histories and ophthalmic
      documentations were obtained from all participants from the two pedigrees.
      Targeted next-generation sequencing (NGS) on 189 genes was performed to screen
      for RP causative mutations in the two families. Two biallelic mutations in EYS,
      p.[R164*];[C2139Y] and p.[W2640*];[F2954S], were identified in the two families,
      respectively. EYS p.R164* and p.F2954S are novel alleles associated with RP,
      while p.C2139Y and p.W2640* are known mutations. Crystal structure modeling on
      the protein eyes shut homolog encoded by the EYS gene revealed abnormal hydrogen
      bonds generated by p.C2139Y and p.F2954S, which would likely affect the
      solubility and cause significant structural changes of the two mutated proteins.
      In conclusion, our study expands the genotypic spectrums for EYS mutations, and
      may provide novel insights into the relevant pathogenesis for RP. We also
      demonstrate targeted NGS approach as a valuable tool for genetic diagnosis. 

PMID- 25753738
TI  - Comparisons of Reproducibility and Mean Values of Diffusion Tensor Imaging
      Derived Indices between Unipolar and Bipolar Diffusion Pulse Sequences.
AB  - Eddy current distortion is an important issue that may influence the quantitative
      measurements of diffusion tensor imaging (DTI). The corrections of eddy current
      artifacts could be performed using bipolar diffusion gradients or unipolar
      gradients with affine registration. Whether the diffusion pulse sequence affects
      the quantification of DTI indices and the technique that produces more reliable
      DTI indices in terms of reproducibility both remain unclear. Therefore, the
      purpose of this study was to compare the reproducibility and mean values of DTI
      derived indices between unipolar and bipolar diffusion pulse sequences based on
      actual human brain data. Five repeated datasets of unipolar and bipolar DTI were
      acquired from 10 healthy subjects at different echo times (TEs). The
      reproducibility and mean values of DTI indices were assessed by calculating the
      coefficient of variation and mean values of the 5 repeated measurements. The
      results revealed that the reproducibility and mean values of DTI indices were
      significantly affected by the pulse sequence. Unipolar DTI exhibited
      significantly higher reproducibility than bipolar DTI even at the same TE, and
      the mean values of DTI indices were significantly different between them.
      Therefore, we concluded that the reproducibility and mean values of DTI indices
      were significantly influenced by diffusion pulse sequences. 

PMID- 25753739
TI  - Inhibition of Cancer Cell Proliferation and Antiradical Effects of Decoction,
      Hydroalcoholic Extract, and Principal Constituents of Hemidesmus indicus R. Br.
AB  - Indian Sarsaparilla (Hemidesmus indicus R. Br.) is widely used in Indian
      traditional medicine. In the present work, we explored the effects of decoction,
      traditional Ayurvedic preparation, and hydroalcoholic extract, a phytocomplex
      more traditionally studied and commercialized as food supplement in western
      medicine, from the roots as possible source of chemicals with new functional
      potential linked to their nutritional uses. The antiproliferative and antioxidant
      properties were assayed. To test antiproliferative affects, different cancer cell
      lines, growing both as monolayers (CaCo2, MCF-7, A549, K562, MDA-MB-231, Jurkat,
      HepG2, and LoVo) and in suspension (K562 and Jurkat) were used. The decoction
      showed strong activity on HepG2 cells, while the hydroalcoholic extracts were
      active on HepG2, LoVo, MCF-7, K562, and Jurkat cell lines. Weak inhibition of
      cancer cell proliferation was observed for the principal constituents of the
      preparations: 2-hydroxy-4-methoxybenzaldehyde, 2-hydroxy-4-methoxybenzoic acid,
      and 3-hydroxy-4-methoxybenzaldehyde that were tested alone. The antiradical
      activity was tested with 2,2-diphenyl-1-picrylhydrazyl and 2,2'-azinobis(3
      ethylbenzothiazoline-6-sulfonic acid)diammonium salt tests and inhibition of
      nitric oxide production in lipopolysaccharide-stimulated RAW 264.7 macrophages.
      Interesting result has also been obtained for hydroalcoholic extract regarding
      genoprotective potential (58.79% of inhibition at 37.5 ug/mL).

PMID- 25753740
TI  - The behavior of benzene confined in a single wall carbon nanotube.
AB  - We present the molecular dynamics study of benzene molecules confined into the
      single wall carbon nanotube. The local structure and orientational ordering of
      benzene molecules are investigated. It is found that the molecules mostly group
      in the middle distance from the axis of the tube to the wall. The molecules
      located in the vicinity of the wall demonstrate some deviation from planar shape.
      There is a tilted orientational ordering of the molecules which depends on the
      location of the molecule. It is shown that the diffusion coefficient of the
      benzene molecules is very small at the conditions we report here.

PMID- 25753741
TI  - Psychological interventions for Common Mental Disorders for People Living With
      HIV in Low- and Middle-Income Countries: systematic review.
AB  - OBJECTIVE: To assess the effectiveness of structured psychological interventions
      against common mental disorders (CMD) in people living with HIV infection (PLWH),
      in low- and middle-income countries (LMIC). METHODS: Systematic review of
      psychological interventions for CMD from LMIC for PLWH, with two-stage screening
      carried out independently by 2 authors. RESULTS: Of 190 studies, 5 met inclusion
      criteria. These were randomised-controlled trials based on the principles of
      cognitive behaviour therapy (CBT) and were effective in reducing CMD symptoms in
      PLWH. Follow-up of study participants ranged from 6 weeks to 12 months with
      multiple tools utilised to measure the primary outcome. Four studies showed a
      high risk of bias, while 1 study from Iran met low risk of bias in all 6 domains
      of the Cochrane risk of bias tool and all 22 items of the CONSORT instrument.
      CONCLUSION: There is a need for more robust and adequately powered studies to
      further explore CBT-based interventions in PLWH. Future studies should report on
      components of the psychological interventions, fidelity measurement and training,
      including supervision of delivering agents, particularly where lay health workers
      are the delivering agent.

PMID- 25753742
TI  - Ikaros and leukaemia.
AB  - The IKZF1 gene at 7p12.2 codes for IKAROS (also termed IKZF1), an essential
      transcription factor in haematopoiesis involved primarily in lymphoid
      differentiation. Its importance is underlined by the fact that deregulation of
      IKAROS results in leukaemia in both mice and men. During recent years,
      constitutional as well as acquired genetic changes of IKZF1 have been associated
      with human disease. For example, certain germline single nucleotide polymorphisms
      in IKZF1 have been shown to increase the risk of some disorders and abnormal
      expression and somatic rearrangements, mutations and deletions of IKZF1
      (DeltaIKZF1) have been detected in a wide variety of human malignancies. Of
      immediate clinical importance is the fact that DeltaIKZF1 occurs in 15% of
      paediatric B-cell precursor acute lymphoblastic leukaemia (BCP ALL) and that the
      presence of DeltaIKZF1 is associated with an increased risk of relapse and a poor
      outcome; in some studies such deletions have been shown to be an independent risk
      factor also when minimal residual disease data are taken into account. However,
      cooperative genetic changes, such as ERG deletions and CRLF2 rearrangements, may
      modify the prognostic impact of DeltaIKZF1, for better or worse. This review
      summarizes our current knowledge of IKZF1 abnormalities in human disease, with an
      emphasis on BCP ALL. 

PMID- 25753743
TI  - Targeting chemokines: Pathogens can, why can't we?
AB  - Chemoattractant cytokines, or chemokines, are the largest sub-family of
      cytokines. About 50 distinct chemokines have been identified in humans. Their
      principal role is to stimulate the directional migration of leukocytes, which
      they achieve through activation of their receptors, following immobilization on
      cell surface glycosaminoglycans (GAGs). Chemokine receptors belong to the G
      protein-coupled 7-transmembrane receptor family, and hence their identification
      brought great promise to the pharmaceutical industry, since this receptor class
      is the target for a large percentage of marketed drugs. Unfortunately, the
      development of potent and efficacious inhibitors of chemokine receptors has not
      lived up to the early expectations. Several approaches to targeting this system
      will be described here, which have been instrumental in establishing paradigms in
      chemokine biology. Whilst drug discovery programs have not yet elucidated how to
      make successful drugs targeting the chemokine system, it is now known that
      certain parasites have evolved anti-chemokine strategies in order to remain
      undetected by their hosts. What can we learn from them? 

PMID- 25753744
TI  - Serum levels of sclerostin in cardiometabolic disorders during pregnancy.
AB  - OBJECTIVE: Sclerostin has recently been introduced as a novel osteocyte-secreted
      factor which is associated with an adverse metabolic profile. However, regulation
      of circulating sclerostin in cardiometabolic disorders during pregnancy including
      gestational diabetes mellitus (GDM) and preeclampsia (PE) has not been
      comprehensively assessed, so far. METHODS: Serum levels of sclerostin were
      quantified in 72 women with GDM and in 72 healthy, pregnant, gestational age
      matched controls (study population 1). Furthermore, circulating sclerostin was
      assessed in 51 women with PE as compared to 51 pregnant controls in a second
      cohort (study population 2). RESULTS: In the first study population (GDM), median
      [interquartile range] sclerostin levels were not significantly different in women
      with GDM as compared to controls (GDM: 19.2 [8.1]pmol/l; controls: 18.6
      [7.1]pmol/l; p=0.906). Interestingly, C reactive protein was a negative and
      independent predictor of circulating sclerostin in the GDM cohort in multivariate
      analysis. In study population 2 (PE), serum levels of sclerostin were not
      different between women with PE and controls (PE: 18.8 [9.2]pmol/l; controls:
      19.3 [8.8]pmol/l; p=0.504). Furthermore, the osteocyte-secreted factor was not
      related to any metabolic and gestational parameter in this cohort. CONCLUSIONS:
      Sclerostin serum levels are not associated with an adverse metabolic profile
      during pregnancy in women with GDM and PE. The physiological significance of
      different associations of circulating sclerostin between pregnancy and non
      pregnant status needs to be determined in future experiments.

PMID- 25753745
TI  - Isolation of a metabolite from the pks island provides insights into colibactin
      biosynthesis and activity.
AB  - Colibactin is a structurally uncharacterized, genotoxic natural product produced
      by commensal and pathogenic strains of E. coli that harbor the pks island. A new
      metabolite has been isolated from a pks(+) E. coli mutant missing an essential
      biosynthetic enzyme. The unusual azaspiro[2.4] bicyclic ring system of this
      molecule provides new insights into colibactin biosynthesis and suggests a
      mechanism through which colibactin and other pks-derived metabolites may exert
      genotoxicity. 

PMID- 25753746
TI  - Transformation obsessions in paediatric obsessive-compulsive disorder: Clinical
      characteristics and treatment response to cognitive behaviour therapy.
AB  - BACKGROUND AND OBJECTIVES: Transformation obsessions denote an under-reported
      symptom of Obsessive Compulsive Disorder (OCD), characterised by an excessive
      fear of turning into another person/object or acquiring unwanted characteristics.
      Relative to other OCD symptoms, little is known about the clinical presentation
      of transformation obsessions. The study aims to examine the clinical correlates
      and treatment prognosis of transformation obsessions in a paediatric OCD sample.
      METHODS: The sample consisted of 346 youths with a primary diagnosis of OCD.
      Patients with and without transformation obsessions were compared in terms of
      demographic and clinical characteristics, and CBT outcomes. RESULTS: 10% of the
      sample endorsed transformation obsessions. Patients with transformation
      obsessions were more likely to be boys, to be on augmented medication regimes,
      and to present with more severe obsessions at assessment. A factor analysis
      identified four major OCD symptom clusters, with transformation obsessions
      loading on a 'forbidden thoughts' factor alongside aggressive, sexual, and
      religious obsessions. No group differences in treatment outcomes were observed.
      LIMITATIONS: Limitations include the cross-sectional and retrospective nature of
      the study, the representativeness of our sample, and use of concomitant
      medication, among others. CONCLUSIONS: The study provides the first empirical
      evidence regarding phenomenological similarities and differences between
      paediatric OCD patients presenting with and without transformation obsessions.
      The findings suggest that transformation obsessions are best conceptualised as
      related to 'forbidden' obsessions and respond to exposure-based CBT.

PMID- 25753747
TI  - Hemithoracic radiation therapy after extrapleural pneumonectomy for malignant
      pleural mesothelioma: Toxicity and outcomes at an Australian institution.
AB  - INTRODUCTION: We aim to report the outcome of patients with malignant pleural
      mesothelioma who underwent extrapleural pneumonectomy (EPP) and adjuvant
      hemithoracic radiotherapy with or without chemotherapy at a single Australian
      institution. METHOD: Between July 2004 and March 2013, 53 patients were referred
      for radiation treatment following EPP, of whom 49 were suitable for adjuvant
      treatment. Radiation treatment initially involved a 3D conformal, mixed
      electron/photon technique, delivering 45-50.4 Gy in 25-28 fractions (31 patients)
      and subsequently a nine-field intensity-modulated radiotherapy technique,
      delivering 50.4-54 Gy in 28-30 fractions (18 patients). Fifty-five per cent of
      patients also received pre-operative chemotherapy. We assessed toxicity, disease
      specific and overall survival in patients who commenced radiation treatment.
      RESULTS: Forty-one patients (84%) completed treatment as prescribed. Six patients
      stopped prematurely due to toxicity, and two with disease progression. Most
      patients discontinuing due to toxicity received over 90% of the prescribed dose.
      Common acute toxicities included nausea, fatigue, anorexia and dermatitis. Severe
      early toxicities were rare. Late toxicities were uncommon, with the exception of
      a persistent elevation in liver enzymes in those with right-sided disease.
      Neither clinical hepatitis nor radiation pneumonitis was documented. With a
      median follow up of 18.7 months, median disease-free and overall survival were
      21.6 and 30.5 months, respectively, and 2-year overall survival was 57.3%.
      CONCLUSION: Hemithoracic radiotherapy following EPP, although associated with
      significant early toxicity, is well tolerated. Most patients complete the
      prescribed treatment, and clinically significant late toxicities are rare.

PMID- 25753748
TI  - Expression of NeuGc on pig heart valves.

PMID- 25753749
TI  - Comparison of heparin and bivalirudin in patients undergoing percutaneous
      coronary intervention without use of glycoprotein IIb/IIIa inhibitors.
AB  - OBJECTIVES: The primary objective of this study is the compare the association
      between bleeding and the use unfractionated heparin (UFH) versus bivalirudin
      during percutaneous coronary intervention (PCI). BACKGROUND: In patients
      undergoing PCI, the risk of bleeding with use of bivalirudin compared with UFH in
      the absence of glycoprotein IIb/IIIa inhibitors is not well defined. METHODS:
      Patients undergoing PCI with either UFH or bivalirudin monotherapy at a single
      institution between 2007 and 2014 were included (n = 6,143). Propensity score
      matching was used to adjust for baseline characteristics yielding 2,984 well
      matched patients (1,492 in each group). The primary endpoint was major non
      coronary artery bypass graft (non-CABG) related bleeding as defined by a Bleeding
      Academic Consortium type 3 or 5. Secondary outcomes included combined major and
      minor bleeding, in-hospital death, periprocedural myocardial infarction, and
      recurrent ischemia requiring urgent revascularization (repeat PCI). RESULTS: In
      the propensity matched cohort, there was no difference in major bleeding between
      UFH and bivalirudin monotherapy (1.8% versus 2.4%, P = 0.305). Combined major and
      minor bleeding was also similar between the two groups (4.3% versus 4.3%, P =
      1.0). Likewise, no differences were observed between the bivalirudin and UFH
      groups in terms of in-hospital death (0.4% versus 0.5%, P = 0.592),
      periprocedural myocardial infarction (1.5% versus 2.0%, P = 0.332) and repeat PCI
      (0.7% versus 0.8%, P = 0.669). CONCLUSION: Among patients undergoing PCI, there
      was no significant difference in rate of bleeding between bivalirudin and heparin
      monotherapy in a real-world setting.

PMID- 25753750
TI  - Acrylamide in Romanian food using HPLC-UV and a health risk assessment.
AB  - The aim of this study was to investigate the level of acrylamide from coffee,
      potato chips and French fries in Romanian food. According to the European Food
      Safety Authority, coffee beans, potato chips and French fries have the highest
      levels of acrylamide. For this survey, 50 samples of coffee beans, 50 samples of
      potato chips and 25 samples of French fries were purchased from different
      producers from the Romanian market. Acrylamide levels have been quantified using
      high-performance liquid chromatography with a diode array detector (HPLC-DAD)
      method, using water as mobile phase. Health risk assessment was achieved by
      computing the average daily intake, hazard quotient, cumulative risk,
      carcinogenic risk and cancer risk. For coffee, potato chips and French fries,
      acrylamide was not shown to pose a health risk in Romanian food. 

PMID- 25753751
TI  - Metagenome sequence of Elaphomyces granulatus from sporocarp tissue reveals
      Ascomycota ectomycorrhizal fingerprints of genome expansion and a Proteobacteria
      rich microbiome.
AB  - Many obligate symbiotic fungi are difficult to maintain in culture, and there is
      a growing need for alternative approaches to obtaining tissue and subsequent
      genomic assemblies from such species. In this study, the genome of Elaphomyces
      granulatus was sequenced from sporocarp tissue. The genome assembly remains on
      many contigs, but gene space is estimated to be mostly complete. Phylogenetic
      analyses revealed that the Elaphomyces lineage is most closely related to
      Talaromyces and Trichocomaceae s.s. The genome of E. granulatus is reduced in
      carbohydrate-active enzymes, despite a large expansion in genome size, both of
      which are consistent with what is seen in Tuber melanosporum, the other sequenced
      ectomycorrhizal ascomycete. A large number of transposable elements are predicted
      in the E. granulatus genome, especially Gypsy-like long terminal repeats, and
      there has also been an expansion in helicases. The metagenome is a complex
      community dominated by bacteria in Bradyrhizobiaceae, and there is evidence to
      suggest that the community may be reduced in functional capacity as estimated by
      KEGG pathways. Through the sequencing of sporocarp tissue, this study has
      provided insights into Elaphomyces phylogenetics, genomics, metagenomics and the
      evolution of the ectomycorrhizal association. 

PMID- 25753752
TI  - Characterization of the p300 Taz2-p53 TAD2 complex and comparison with the p300
      Taz2-p53 TAD1 complex.
AB  - The p53 tumor suppressor is a critical mediator of the cellular response to
      stress. The N-terminal transactivation domain of p53 makes protein interactions
      that promote its function as a transcription factor. Among those cofactors is the
      histone acetyltransferase p300, which both stabilizes p53 and promotes local
      chromatin unwinding. Here, we report the nuclear magnetic resonance solution
      structure of the Taz2 domain of p300 bound to the second transactivation
      subdomain of p53. In the complex, p53 forms an alpha-helix between residues 47
      and 55 that interacts with the alpha1-alpha2-alpha3 face of Taz2. Mutational
      analysis indicated several residues in both p53 and Taz2 that are critical for
      stabilizing the interaction. Finally, further characterization of the complex by
      isothermal titration calorimetry revealed that complex formation is pH-dependent
      and releases a bound chloride ion. This study highlights differences in the
      structures of complexes formed by the two transactivation subdomains of p53 that
      may be broadly observed and play critical roles in p53 transcriptional activity. 

PMID- 25753753
TI  - Comparison between single-molecule and X-ray crystallography data on yeast F1
      ATPase.
AB  - Single molecule studies in recent decades have elucidated the full chemo
      mechanical cycle of F1-ATPase, mostly based on F1 from thermophilic bacteria. In
      contrast, high-resolution crystal structures are only available for mitochondrial
      F1. Here we present high resolution single molecule rotational data on F1 from
      Saccharomyces cerevisiae, obtained using new high throughput detection and
      analysis tools. Rotational data are presented for the wild type mitochondrial
      enzyme, a "liver" isoform, and six mutant forms of yeast F1 that have previously
      been demonstrated to be less efficient or partially uncoupled. The wild-type and
      "liver" isoforms show the same qualitative features as F1 from Escherichia coli
      and thermophilic bacteria. The analysis of the mutant forms revealed a delay at
      the catalytic dwell and associated decrease in Vmax, with magnitudes consistent
      with the level of disruption seen in the crystal structures. At least one of the
      mutant forms shows a previously un-observed dwell at the ATP binding angle,
      potentially attributable to slowed release of ADP. We discuss the correlation
      between crystal structures and single molecule results. 

PMID- 25753755
TI  - Caregiving Experience for Children with Intellectual Disabilities among Parents
      in a Developing Area in China.
AB  - BACKGROUND: By utilizing grounded theory methodology, this study attempted to
      fill a gap whereby little research explored family caregiving perspectives in
      China where public support is insufficient and familial responsibility is highly
      valued. METHODS: Data were collected through the qualitative methods of
      interviews and observations among a purposive sample of 15 parents of children
      with intellectual disabilities in central China. RESULTS: The central idea
      emerging from the data encompassed five broad categories of caregiving
      experiences: (i) unavoidable caregiving responsibility and (ii) uncertain future
      as the greatest worries which are the perception towards the recipient; (iii)
      compromising quality of life and (iv) positive roles of caregiving tasks which
      focus on the self; and (v) community support which is the perceived support from
      the external system. CONCLUSION: A recursive relationship existed among these
      categories. Chinese culture and traditional beliefs dominated throughout these
      issues. The implications and limitations of this study were discussed.

PMID- 25753754
TI  - Fluocinolone Acetonide Is a Potent Synergistic Factor of TGF-beta3-Associated
      Chondrogenesis of Bone Marrow-Derived Mesenchymal Stem Cells for Articular
      Surface Regeneration.
AB  - Articular cartilage repair remains a challenging problem. Based on a high
      throughput screening and functional analysis, we found that fluocinolone
      acetonide (FA) in combination with transforming growth factor beta 3 (TGF-beta3)
      strongly potentiated chondrogenic differentiation of human bone marrow-derived
      mesenchymal stem cells (hBMSCs). In an in vivo cartilage defect model in knee
      joints of immunocompromised mice, transplantation of FA/TGF-beta3-treated hBMSCs
      could completely repair the articular surface. Analysis of the intracellular
      pathways revealed that FA enhanced TGF-beta3-induced phosphorylation of Smad2 and
      Smad3. Additionally, we performed a pathway array and found that FA activates the
      mTORC1/AKT pathway. Chemical inhibition of mTORC1 with rapamycin substantially
      suppressed FA effect, and inhibition of AKT completely repressed chondrogenesis
      of hBMSCs. Inhibition of glucocorticoid receptor with mifepristone also
      suppressed FA effect, suggesting that FA involves binding to the glucocorticoid
      receptor. Comparative analysis with other glucocorticoids (triamcinolone
      acetonide [TA] and dexamethasone [DEX]) revealed the unique ability of FA to
      repair articular cartilage surgical defects. Analysis of intracellular pathways
      showed that the mTORC1/AKT pathway and the glucocorticoid receptor was highly
      activated with FA and TA, but to a lesser extent with DEX. Collectively, these
      results show a unique ability of FA to enhance TGF-beta3-associated
      chondrogenesis, and suggest that the FA/TGF-beta3 combination may be used as
      major inducer of chondrogenesis in vitro. Additionally, FA/TGF-beta3 could be
      potentially applied in a clinical setting to increase the efficiency of
      regenerative approaches based on chondrogenic differentiation of stem cells.

PMID- 25753756
TI  - Physical characterization and in vitro biological impact of highly aggregated
      antibodies separated into size-enriched populations by fluorescence-activated
      cell sorting.
AB  - An IgG2 monoclonal antibody (mAb) solution was subjected to stirring, generating
      high concentrations of nanometer and subvisible particles, which were then
      successfully size-enriched into different size bins by low-speed centrifugation
      or a combination of gravitational sedimentation and fluorescence-activated cell
      sorting (FACS). The size-fractionated mAb particles were assessed for their
      ability to elicit the release of cytokines from a population of donor-derived
      human peripheral blood mononuclear cells (PBMC) at two phases of the immune
      response. Fractions enriched in nanometer-sized particles showed a lower response
      than those enriched in micron-sized particles in this assay. Particles of 5-10
      MUm in size displayed elevated cytokine release profiles compared with other size
      ranges. Stir-stressed mAb particles had amorphous morphology, contained protein
      with partially altered secondary structure, elevated surface hydrophobicity
      (compared with controls), and trace levels of elemental fluorine. FACS size
      enriched the mAb particle samples, yet did not notably alter the overall
      morphology or composition of particles as measured by microflow imaging,
      transmission electron microscopy, and scanning electron microscopy-energy
      dispersive X-ray spectroscopy. The utility and limitations of FACS for size
      separation of mAb particles and potential of in vitro PBMC studies to rank-order
      the immunogenic potential of various types of mAb particles are discussed.

PMID- 25753757
TI  - Intrauterine insemination practice and the UK NICE guidelines.

PMID- 25753758
TI  - In search for better pharmacological prophylaxis for acute mountain sickness:
      looking in other directions.
AB  - Despite decades of research, the exact pathogenic mechanisms underlying acute
      mountain sickness (AMS) are still poorly understood. This fact frustrates the
      search for novel pharmacological prophylaxis for AMS. The prevailing view is that
      AMS results from an insufficient physiological response to hypoxia and that
      prophylaxis should aim at stimulating the response. Starting off from the
      opposite hypothesis that AMS may be caused by an initial excessive response to
      hypoxia we suggest that directly or indirectly blunting specific parts of the
      response might provide promising research alternatives. This reasoning is based
      on the observations that 1) humans, once acclimatized, can climb Mt Everest
      experiencing arterial partial oxygen pressures (PaO2 ) as low as 25 mmHg without
      AMS symptoms, 2) paradoxically AMS usually develops at much higher PaO2 levels,
      and 3) several biomarkers, suggesting initial activation of specific pathways at
      such PaO2 , are correlated with AMS. Apart from looking for substances that
      stimulate certain hypoxia triggered effects, such as the ventilatory response to
      hypoxia, we suggest to also investigate pharmacological means aiming at blunting
      certain other specific hypoxia activated pathways, or stimulating their agonists,
      in the quest for better pharmacological prophylaxis for AMS. This article is
      protected by copyright. All rights reserved.

PMID- 25753760
TI  - Nickel phosphine catalysts with pendant amines for electrocatalytic oxidation of
      alcohols.
AB  - Nickel phosphine complexes with pendant amines have been found to be
      electrocatalysts for the oxidation of primary and secondary alcohols, with
      turnover frequencies as high as 3.3 s(-1). These complexes are the first
      electrocatalysts for alcohol oxidation based on non-precious metals, which will
      be critical for use in fuel cells. 

PMID- 25753759
TI  - Binding of the monoclonal antibody RP215 to immunoglobulin G in metastatic lung
      adenocarcinomas is correlated with poor prognosis.
AB  - AIMS: Cancer cell-derived immunoglobulin (Ig)G (cancer-IgG) has been found to be
      involved in the pathogenesis and progression of many cancers, including lung
      cancer. The aim of the present study was to investigate the relationship between
      cancer-IgG expression in lung adenocarcinoma (ADC) and clinicopathological
      characteristics and clinical outcome. METHODS AND RESULTS: Immunohistochemical
      analysis was performed using an RP215 monoclonal antibody to determine cancer-IgG
      expression in 140 lung ADC patients. Cell migration and invasion were analysed in
      A549 cell line after short interfering RNA (siRNA) knockdown of IgG and cell
      sorting by flow cytometry. Our results show that RP215 immunostaining score is
      correlated significantly with local invasion (P < 0.05) and tumour
      differentiation (P < 0.05) in ADC. Moreover, RP215 staining was significantly
      higher in metastatic tumours than in primary tumours (P < 0.0001). The knockdown
      of IgG resulted in a reduction of cell migration and invasion. In contrast, RP215
      positive cells displayed greater migration and invasion ability than RP215
      negative cells. Additionally, a higher RP215 immunostaining score was associated
      significantly with poor prognosis. CONCLUSIONS: RP215 staining is correlated
      strongly with differentiation, local invasion, metastasis and clinical outcome of
      patients with lung ADC. Our results suggest that RP215 can serve as a biomarker
      for prognosis of lung ADC.

PMID- 25753761
TI  - Social cognitive theory correlates of moderate-intensity exercise among adults
      with type 2 diabetes.
AB  - The purpose of this study was to identify social cognitive theory (SCT)
      correlates of moderate- to vigorous-intensity exercise (MVPA) among adults with
      type 2 diabetes. Adults with type 2 diabetes (N = 181) participated in the study.
      Participants were recruited through ResearchMatch.org to complete an online
      survey. The survey used previously validated instruments to measure dimensions of
      self-efficacy, self-regulation, social support, outcome expectations, the
      physical environment, and minutes of MVPA per week. Spearman Rank Correlations
      were used to determine the relationship between SCT variables and MVPA.
      Classification and Regression Analysis using a decision tree model was used to
      determine the amount of variance in MVPA explained by SCT variables. Due to low
      levels of vigorous activity, only moderate-intensity exercise (MIE) was analyzed.
      SCT variables explained 42.4% of the variance in MIE. Self-monitoring, social
      support from family, social support from friends, and self-evaluative outcome
      expectations all contributed to the variability in MIE. Other contributing
      variables included self-reward, task self-efficacy, social outcome expectations,
      overcoming barriers, and self-efficacy for making time for exercise. SCT is a
      useful theory for identifying correlates of MIE among adults with type 2
      diabetes. The SCT correlates can be used to refine diabetes education programs to
      target the adoption and maintenance of regular exercise. 

PMID- 25753762
TI  - Presentation of meta-analysis plots.
AB  - Meta-analysis (forest) plots are widely used to show the results from multiple
      individual randomized trials or observational studies that address the same
      question, including the assessment of screening markers. They show the between
      study spread of results and provide a summary estimate of the results from all
      the studies combined. We here illustrate the advantage of ordering study results
      by the magnitude of the effect and including a vertical shaded band encompassing
      the summary 95% confidence interval of the summary estimate to emphasize the
      uncertainty of the estimate in a way that is more prominent than only displaying
      a "diamond" around its value. 

PMID- 25753763
TI  - Detection of Clostridium botulinum in liquid manure and biogas plant wastes.
AB  - Biogas plants have been considered as a source for possible amplification and
      distribution of pathogenic bacteria capable of causing severe infections in
      humans and animals. Manure and biogas wastes could be sources for spore-forming
      bacteria such as Clostridium botulinum. In the present study, 24 liquid manure
      and 84 biogas waste samples from dairies where the majority of the cows suffered
      from chronic botulism were investigated for the presence of botulinum neurotoxins
      (BoNT) and C. botulinum spores. The prevalence of BoNT/A, B, C, D, and E in
      biogas wastes was 16.6, 8.3, 10.7, 7.1, and 10.8 %, respectively, while in
      manure, the prevalence was 0.0, 0.0, 0.0, 8.3, and 4.1 %, respectively. After
      enrichment of samples in reinforced cultural medium, they were tested for C.
      botulinum BoNT/A, B, C, D, and E using ELISA (indirect C. botulinum detection).
      The prevalence of C. botulinum type A, B, C, D, and E samples in biogas wastes
      was 20.2, 15.5, 19, 10.7, and 34.8 %, respectively, while the prevalence in
      liquid manure was 0.0, 0.0, 0.0, 8.3, and 12.5 %, respectively. In conclusion,
      the occurrence of BoNT and C. botulinum spores in biogas waste of diseased
      animals indicates an increased and underestimated hygienic risk. Application of
      digestates from biogas fermentations as fertilizers could lead to an accumulation
      of long lifespan spores in the environment and could be a possible health hazard.

PMID- 25753764
TI  - Resistive Switching Memory Devices Based on Proteins.
AB  - Resistive switching memory constitutes a prospective candidate for next
      generation data storage devices. Meanwhile, naturally occurring biomaterials are
      promising building blocks for a new generation of environmentally friendly,
      biocompatible, and biodegradable electronic devices. Recent progress in using
      proteins to construct resistive switching memory devices is highlighted. The
      protein materials selection, device engineering, and mechanism of such protein
      based resistive switching memory are discussed in detail. Finally, the critical
      challenges associated with protein-based resistive switching memory devices are
      presented, as well as insights into the future development of resistive switching
      memory based on natural biomaterials. 

PMID- 25753765
TI  - A Comparison of the Efficacy and Adverse Effects of Double-Lumen Endobronchial
      Tubes and Bronchial Blockers in Thoracic Surgery: A Systematic Review and Meta
      analysis of Randomized Controlled Trials.
AB  - OBJECTIVE: To compare the efficacy and adverse effects of using bronchial
      blockers (BBs) and double-lumen endobronchial tubes (DLTs). DESIGN: Systematic
      review and meta-analysis of randomized controlled trials (RCTs) comparing BBs and
      DLTs. SETTING: Hospital units undertaking thoracic surgery PARTICIPANTS: Patients
      undergoing thoracic surgery requiring lung isolation. INTERVENTIONS: BBs and
      DLTs. MEASUREMENTS AND MAIN RESULTS: A systematic literature search was conducted
      for RCTs comparing BBs and DLTs using Google Scholar, Ovid Medline, and Cochrane
      library databases up to October 2013. Inclusion criteria were RCTs comparing BBs
      and DLTs, intubation carried out by qualified anesthesiologists or trainee
      specialists, outcome measures relating to either efficacy or adverse effects.
      Studies that were inaccessible in English were excluded. Mantel-Haenszel fixed
      effect meta-analysis of recurring outcome measures was performed using RevMan 5
      software. The search produced 39 RCTs published between 1996 and 2013. DLTs were
      quicker to place (mean difference: 51 seconds, 95% confidence intervals [CI] 8-94
      seconds; p = 0.02) and less likely to be incorrectly positioned (odds ratio [OR]
      2.70; 95% CI 1.18-6.18, p = 0.02) than BBs. BBs were associated with fewer
      patients having a postoperative sore throat (OR 0.39, 95% CI: 0.23-0.68, p =
      0.0009), less hoarseness (OR: 0.43,95%, CI 0.24-0.75, p = 0.003), and fewer
      airway injuries (OR 0.40, 95% CI 0.21-0.75, p = 0.005) than DLTs. CONCLUSION:
      While BBs are associated with a lower incidence of airway injury and a lower
      severity of injury, DLTs can be placed quicker and more reliably.

PMID- 25753766
TI  - Lifestyle modification increases serum testosterone level and decrease central
      blood pressure in overweight and obese men.
AB  - Obesity has reached global epidemic proportions and is associated with multiple
      comorbidities, including cardiovascular disease. A novel predictor of
      cardiovascular disease is elevated central systolic blood pressure. In fact,
      lifestyle modifications have been shown to decrease the central systolic blood
      pressure in overweight and obese men. The mechanism underlying these changes has
      yet to be fully elucidated. Interestingly, testosterone has been found to have
      cardioprotective effects. Moreover, serum testosterone levels are lower in obese
      men than in normal weight men. However, it is still unclear whether testosterone
      participates in the decrease of central blood pressure in overweight and obese
      men following lifestyle modifications. So, the purpose of the present study was
      to investigate the effect of testosterone on central systolic blood pressure in
      overweight and obese men before and after the 12-week lifestyle modification
      program. Forty-four overweight and obese men completed a 12-week lifestyle
      modification program (aerobic exercise training and dietary modifications). For
      all participants, central systolic blood pressure and serum testosterone levels
      were measured before and after the program. After the program, central systolic
      blood pressure was significantly decreased while serum total testosterone levels
      were significantly increased in overweight and obese men. Moreover, we also found
      a significant negative relationship between the change in serum testosterone
      levels and that in central systolic blood pressure. The present study suggests
      that increased serum testosterone levels likely contribute to a decrease in
      central blood pressure in overweight and obese men. 

PMID- 25753767
TI  - Interleukin-27 improves the ability of adenosine deaminase to rule out
      tuberculous pleural effusion regardless of pleural tuberculosis prevalence.
AB  - BACKGROUND: Interleukin-27 (IL-27) has been proposed to be useful for diagnosing
      tuberculous pleural effusion (TPE). Adenosine deaminase (ADA) has been long used
      for the same purpose. The aim of this study was to compare the performance of IL
      27, ADA, and their product (IL-27 * ADA) in the diagnosis of TPE. METHODS:
      Pleural fluid samples from patients with exudative pleural effusions were
      assessed for IL-27 and ADA levels. Receiver operating characteristic (ROC) curves
      were constructed to compare the overall diagnostic accuracy of IL-27, ADA, and IL
      27 * ADA. Curves of false-positive (FPR) and false-negative (FNR) rates as a
      function of TPE prevalence were also constructed, and mean rates of false results
      in low (1-10%), intermediate (11-40%), and high (41-70%) prevalences were
      estimated to evaluate the ability of the three markers in ruling in or ruling out
      TPE. RESULTS: We studied 121 exudates. IL-27 and ADA were higher in TPEs compared
      with non-TPEs and they presented similar accuracies for the diagnosis of TPE. The
      product of IL-27 and ADA (IL-27 * ADA) was more accurate than ADA for the same
      purpose. IL-27 and IL-27 * ADA presented the lowest overall FPR and FNR,
      respectively. The FPR of IL-27, ADA and IL-27 * ADA was > 9%, even in high
      prevalence settings. Although their FNR was < 2% in low prevalence settings, only
      IL-27 * ADA exhibited sufficiently low FNR (< 1%) in intermediate and high
      prevalences. CONCLUSIONS: ADA, IL-27, and IL-27 * ADA cannot reliably 'rule in'
      TPE in any prevalence setting. TPE can be 'ruled out' by each of the biomarkers
      in low prevalence settings. In intermediate and high prevalence settings, IL-27 *
      ADA is a reliable 'rule out' test in the diagnostic approach to TPEs.

PMID- 25753768
TI  - Even high-dose extended infusions may not yield desired concentrations of beta
      lactams: the value of therapeutic drug monitoring.
AB  - A 35-year-old patient in intensive care with severe burn injury developed
      episodes of sepsis. Blood culture yielded a multidrug-resistant Pseudomonas
      aeruginosa and treatment was commenced with amikacin (minimum inhibitory
      concentration (MIC) 2-4 mg/L, dose 20 mg/kg adjusted body weight 24-hourly) and
      meropenem (MIC 8 mg/L, dose 2 g IV 8-hourly and later 6-hourly). Despite the use
      of extended infusions with beta-lactam therapeutic drug monitoring and doses that
      were more than 2.5 times higher than standard meropenem doses, resistance
      emerged. This case report describes the application of therapeutic drug
      monitoring to optimize beta-lactam therapy in a difficult-to-treat critically ill
      patient. 

PMID- 25753769
TI  - The experience of learning to speak up: a narrative inquiry on newly graduated
      registered nurses.
AB  - AIMS AND OBJECTIVES: To explore the process of learning to speak up in practice
      among newly graduated registered nurses. BACKGROUND: Speaking up is an important
      aspect of communication to ensure patient safety within a healthcare team.
      However, nurses have reported being hesitant about speaking up or being unable to
      be heard, despite adopting various safety tools. A power differential could be a
      factor in their hesitation to speak up. While a large number of new graduates are
      employed in the lower rungs of the hospital hierarchy to resolve local and global
      nursing shortages, the process of their learning to speak up remains under
      explored. DESIGN: The narrative concept of experience is addressed through the
      three-dimensional space of a narrative inquiry. METHODS: Eighteen new graduates
      were recruited. Stories of experiences of speaking up emerged naturally during
      repeated unstructured interviews and ongoing email conversations with three
      participants. RESULTS: The complex process of learning to speak up is
      schematically represented. Three interrelated narrative threads were identified:
      (1) learning to speak up requires more than one-off training and safety tools,
      (2) mentoring speaking up in the midst of educative and miseducative experiences
      and (3) making public spaces safe for telling secret stories. CONCLUSIONS:
      Speaking up requires ongoing mentoring to see new possibilities for sustaining
      professional identities in the midst of miseducative experiences under the
      potential shaping of the Chinese culture and generational differences.
      Appreciative inquiry might be a new approach that can be used to promote positive
      cultural changes to encourage newly graduated registered nurses to learn to speak
      up to ensure patient safety. RELEVANCE TO CLINICAL PRACTICE: Cultivating a safe
      and open culture of communication and mentoring new graduates to speak up will
      benefit patient safety now and in the future by helping to retain committed
      patient advocates who could mentor future generations.

PMID- 25753770
TI  - Inequalities in dental caries among 12-year-old Chinese children.
AB  - OBJECTIVE: To explore whether there are socioeconomic, ethnic, and geographical
      inequalities in dental caries among 12-year-old Chinese children. METHODS: Data
      from 2,307 12-year-old children living in Guangxi, Hubei, Jilin, and Shanxi and
      who participated in the Third National Oral Health Survey in China were used for
      this study. Data were collected through structured questionnaires and clinical
      examinations with children. The decayed, missing, and filled permanent teeth
      (DMFT) index and number of decayed teeth (DT) were the outcome measures for
      analysis. Inequalities in DMFT and DT by socioeconomic position (parental
      education), ethnicity, and geography (province of residence and urbanicity) were
      assessed in unadjusted and adjusted negative binomial regression models. RESULTS:
      Ethnicity and geographical factors, but not parental education, were
      significantly associated with childhood dental caries in unadjusted models.
      However, only geographical factors remained significantly related to dental
      caries after mutual adjustments. The DMFT index and DT were higher among children
      living in Jilin and Guangxi than those of children living in Hubei and Shanxi,
      and also higher among children living in rural areas than in those living in
      urban areas. CONCLUSION: This analysis shows inequalities in dental caries among
      12-year-old children in four provinces of China. There were considerable
      inequalities in children's DMFT and number of decayed teeth by geography but not
      by ethnicity or parental education.

PMID- 25753773
TI  - Evaluating the effectiveness of knowledge brokering in health research: a
      systematised review with some bibliometric information.
AB  - OBJECTIVE: The aim of this study was to identify the effectiveness of knowledge
      brokering as a knowledge translation (KT) strategy used in promoting evidence
      based decision-making, evidence-based practice or collaboration between
      researchers, health practitioners and policymakers. METHODS: A systematised
      review of literature was performed using MEDLINE (through ProQuest Dialog),
      PubMed and Scopus electronic databases. A search strategy was developed to
      identify primary studies indexed in these databases on knowledge translation that
      reported the implementation of knowledge brokering. Sixty-two titles related to
      knowledge brokering were identified from the search after the removal of
      duplicates, and 24 articles met the eligibility criteria following the review of
      the full text documents. The findings were then synthesised using a narrative
      approach. RESULTS: It was found that knowledge brokering has been an effective
      strategy for knowledge translation. CONCLUSION: Although this review shows that
      knowledge brokering has been an effective strategy for KT, it advocates for more
      empirical studies to compare the effectiveness of specific knowledge brokering
      approaches with others. It also calls for empirical studies to explicate the role
      of library and information science professionals in knowledge brokering.

PMID- 25753771
TI  - Senescence of human skin-derived precursors regulated by Akt-FOXO3
      p27(KIP1)/p15(INK4b) signaling.
AB  - Multipotent skin-derived precursors (SKPs) are dermal stem cells with the
      capacity to reconstitute the dermis and other tissues, such as muscles and the
      nervous system. Thus, the easily available human SKPs (hSKPs) hold great promises
      in regenerative medicine. However, long-term expansion is difficult for hSKPs in
      vitro. We previously demonstrated that hSKPs senesced quickly under routine
      culture conditions. To identify the underlying mechanisms so as to find an
      effective way to expand hSKPs, time-dependent microarray analysis of gene
      expression in hSKPs during in vitro culture was performed. We found that the
      senescence of hSKPs had a unique gene expression pattern that differs from
      reported typical senescence. Subsequent investigation ruled out the role of DNA
      damage and classical p53 and p16(INK4a) signaling in hSKP senescence. Examination
      of cyclin-dependent kinase inhibitors revealed the involvement of p15(INK4b) and
      p27(KIP1). Further exploration about upstream signals indicated the contribution
      of Akt hypo-activity and FOXO3 to hSKP senescence. Forced activation of Akt and
      knockdown of FOXO3, p15(INK4b) and p27(KIP1) effectively inhibited hSKP
      senescence and promoted hSKP proliferation. The unique senescent phenotype of
      human dermal stem cells and the role of Akt-FOXO3-p27(KIP1)/p15(INK4b) signaling
      in regulating hSKP senescence provide novel insights into the senescence and self
      renewal regulation of adult stem cells. The present study also points out a way
      to propagate hSKPs in vitro so as to fulfill their promises in regenerative
      medicine.

PMID- 25753774
TI  - DWI using navigated interleaved multishot EPI with realigned GRAPPA
      reconstruction.
AB  - PURPOSE: A novel k-space reconstruction method is proposed for generating
      diffusion-weighted imaging (DWI) using navigated interleaved multishot EPI
      (msEPI). THEORY AND METHODS: In interleaved msEPI, each shot of data acquired
      from one coil channel is a subset of the full k-space of that channel. All the k
      space subsets of one channel can be treated as an undersampled dataset of a
      virtual multichannel data, which can be reconstructed by the GRAPPA algorithm
      after k-space realignment. The intershot phase variations are directly
      compensated using navigator echoes as the auto-calibrating data in GRAPPA
      reconstruction. In cases of multichannel msEPI data, all the virtual channels and
      actual channels can be integrated into a single GRAPPA reconstruction step. The
      proposed method is tested using both simulation and in-vivo data. The simulation
      results produced by the proposed method and a SENSE-based method are compared.
      RESULTS: The simulated images generated by the proposed method exhibit less
      relative error compared with those generated by the SENSE method. Inconsistent
      shot-to-shot phase variation is naturally resolved by GRAPPA calibration without
      additional phase map processing. High-quality brain DWI with submillimeter
      resolution is obtained using our proposed reconstruction method. CONCLUSION: A
      novel k-space msEPI reconstruction method has been developed for generating high
      quality diffusion imaging.

PMID- 25753772
TI  - Concealment of lung cancer diagnosis: prevalence and correlates.
AB  - BACKGROUND: Lung cancer has a commonly understood behavioral etiology. Thus, lung
      cancer patients are often blamed for their illness and may seek to avoid this
      blame by concealing their diagnosis from others. This study sought to determine
      the prevalence of concealment and identify demographic, clinical, and
      psychosocial correlates of concealment among lung cancer patients. METHODS: A
      sample of 117 lung cancer patients receiving chemotherapy for non-small cell or
      small cell lung cancer was recruited and completed self-report demographic
      questionnaires, a measure of diagnosis concealment designed and pilot tested for
      this study, and standard measures of psychosocial variables. Clinical factors
      were assessed via a medical chart review. RESULTS: Thirty participants (26%)
      reported concealing their diagnosis in the previous month, most frequently from
      casual friends and close friends. Reported reasons for concealment largely
      reflected concern for others. Univariate analyses indicated that those who
      concealed their lung cancer diagnosis reported more internalized shame related to
      their illness and use of positive reappraisal as a coping strategy (ps <= 0.02).
      In addition, those who concealed were more likely to have used alcohol in the
      previous month and have a more recent recurrence, among those who had a
      recurrence (ps <= 0.04). Multivariate analyses indicated that internalized shame
      and use of positive reappraisal accounted for significant unique variance in
      concealment above and beyond that accounted for by use of alcohol (ps < 0.05).
      CONCLUSIONS: Future research should aim to replicate and extend these findings
      with longitudinal designs to elucidate the directionality of the associations
      observed in this study.

PMID- 25753775
TI  - West Nile Disease Epidemiology in North-West Africa: Bibliographical Review.
AB  - West Nile fever (WNF) or West Nile disease (WND) is a mosquito-borne viral
      disease that can affect birds, humans and horses. West Nile virus (WNV) is a
      member of the genus Flavivirus in the family Flaviviridae. WNV is maintained in a
      mosquito-bird-mosquito transmission cycle, whereas humans and horses are
      considered dead-end hosts. In human and horses, symptoms range from unapparent
      infection to mild febrile illness, meningitis, encephalitis or death. WNV has a
      wide geographical range that includes portions of Europe, Asia, Africa, Australia
      (Kunjin virus), and in North, Central and South America. Migratory birds are
      thought to be primarily responsible for virus dispersal, including reintroduction
      of WNV from endemic areas into regions that experience sporadic outbreaks (Fields
      Virology, 2001, Lippincott Williams and Wilkins, Philadelphia, Pennsylvania, USA,
      1043-1125). The occurrence of disease in humans and animals along with birds and
      mosquitoes surveillance for WNV activity demonstrates that the virus range has
      dramatically expanded including North, Central and South America as well as
      Europe and countries facing the Mediterranean Basin. WND infection in humans has
      been reported in Morocco in 1996 (Virologie, 1, 1997, 248), in Tunisia in 2007
      (Ann. N. Y. Acad., 951, 2001, 117) (Med. Trop., 61, 2001, 487) and 2003
      (Epidemiologie de la fievre West Nile, 2012, These de doctorat, Universite
      Montpellier II, Sciences et techniques du Langueduc, Montpellier, France), and in
      Algeria in 1994 (Rev. Sci. Tech., 31, 2012, 829). Outbreaks of equine
      encephalitis have been also reported in Morocco in 1996 (Bull. OIE, 11, 1996,
      867), in 2003 (Emerg. Infect. Dis., 11, 2005, 306) and in 2010 (World Animal
      Health Information Database. WAHID, 2010). Serological evidence of WNV has been
      demonstrated in the three countries in many species. The aim of this review was
      to assess the epidemiological situation of WND in north-west Africa comprising
      Morocco, Algeria and Tunisia, with an updated literature review based on of human
      cases and equine outbreaks reports as well as serological studies in these
      countries.

PMID- 25753776
TI  - A single set of exhaustive exercise before resistance training improves muscular
      performance in young men.
AB  - PURPOSE: The purpose of this study was to examine the effects of an additional
      set of exhaustive exercise before traditional hypertrophic training on quadriceps
      muscle performance in young men. METHODS: Subjects performed maximal dynamic
      strength (1RM), local muscular endurance (LME), and magnetic resonance imaging
      (MRI) tests before and after an 8-week hypertrophic training program using a knee
      extensor machine. After baseline testing, the subjects were divided into 3
      groups: untrained control, traditional training (TR), and prior exhaustive
      training (PE). Both the TR and PE groups trained using the same training protocol
      (2 days week(-1); 3 sets of 8-12 repetitions at 75 % of 1RM); the only difference
      was that the PE group performed an additional set of exhaustive exercise at 20 %
      of 1RM before each training session. RESULTS: After 8 weeks, the PE group
      experienced a greater (P < 0.05) increase in 1RM, cross-sectional area, and LME
      than the TR group. Additionally, no changes (P > 0.05) in daily dietary intake
      were observed between groups. CONCLUSION: These results suggest that the
      inclusion of a single set of exhaustive exercise at 20 % of 1RM before
      traditional hypertrophic training can be a suitable strategy for inducing
      additional beneficial effects on quadriceps strength, hypertrophy, and endurance
      in young men.

PMID- 25753778
TI  - A case of multiple eccrine hidrocystoma successfully treated with oral
      oxybutynin.

PMID- 25753777
TI  - Heterogeneity of genetic architecture of body size traits in a free-living
      population.
AB  - Knowledge of the underlying genetic architecture of quantitative traits could aid
      in understanding how they evolve. In wild populations, it is still largely
      unknown whether complex traits are polygenic or influenced by few loci with major
      effect, due to often small sample sizes and low resolution of marker panels.
      Here, we examine the genetic architecture of five adult body size traits in a
      free-living population of Soay sheep on St Kilda using 37 037 polymorphic SNPs.
      Two traits (jaw and weight) show classical signs of a polygenic trait: the
      proportion of variance explained by a chromosome was proportional to its length,
      multiple chromosomes and genomic regions explained significant amounts of
      phenotypic variance, but no SNPs were associated with trait variance when using
      GWAS. In comparison, genetic variance for leg length traits (foreleg, hindleg and
      metacarpal) was disproportionately explained by two SNPs on chromosomes 16
      (s23172.1) and 19 (s74894.1), which each explained >10% of the additive genetic
      variance. After controlling for environmental differences, females heterozygous
      for s74894.1 produced more lambs and recruits during their lifetime than females
      homozygous for the common allele conferring long legs. We also demonstrate that
      alleles conferring shorter legs have likely entered the population through a
      historic admixture event with the Dunface sheep. In summary, we show that
      different proxies for body size can have very different genetic architecture and
      that dense SNP helps in understanding both the mode of selection and the
      evolutionary history at loci underlying quantitative traits in natural
      populations. 

PMID- 25753779
TI  - Exosomal RNA from Mycobacterium tuberculosis-Infected Cells Is Functional in
      Recipient Macrophages.
AB  - Exosomes are extracellular vesicles released by cells that carry proteins, lipids
      and nucleic acids and function in intercellular communication. Previously, we
      determined that exosomes released from Mycobacterium tuberculosis (M.tb)-infected
      macrophages carry mycobacterial proteins and lipids. However, the RNA composition
      within these exosomes has not been defined. In this study, we characterized the
      exosomes released from M.tb-infected macrophages and identified a cohort of mouse
      messenger RNA (mRNA) and microRNA (miRNA). Quantitative reverse-transcriptase
      polymerase chain reaction analysis showed less abundance of miRNAs in exosomes
      released from infected compared with uninfected macrophages. Moreover, more than
      100 transcripts were found to be enriched or unique to exosomes from infected
      cells including transcripts involved in regulating an immune response. The
      exosomal RNA could be transferred and expressed in naive macrophages and was
      biologically active, stimulating production of inflammatory mediators and
      inducing apoptosis in recipient cells. Interestingly, we also identified
      mycobacterial transcripts in exosomes released from infected macrophages. To our
      knowledge, this is the first study to identify bacterial-derived RNA in exosomes.
      Our results suggest that exosomal RNA released from M.tb-infected macrophages may
      have functional and diagnostic potential in the context of a mycobacterial
      infection. 

PMID- 25753780
TI  - Comparison of the cytotoxic impact of chlorfluazuron on selected insect and human
      cell lines.
AB  - To gain new insight into the mechanism of selective cytotoxicity of benzoylureas
      as insecticides, the in vitro mode of action of chlorfluazuron was investigated
      on lepidopteran Tn5B1-4 and Sf-21 cells and human Hek293 and HepG2 cells.
      Chlorfluazuron inhibited the proliferation of Tn5B1-4 and Sf-21 cells with 50%
      inhibitory concentration values (IC50) of 4.96 uM and 1.12 uM at 48 h and 2.37 uM
      and 1.76 uM at 96 h, respectively, versus that of Hek293 and HepG2 cells with
      IC50 values >20 uM. When transferred to chlorfluazuron-free medium, lepidopteran
      Tn5B1-4 and Sf-21 cells had a postinhibitory recovery development period within
      24 h followed by a suppressed increase in cell viability, but human Hek293 and
      HepG2 cells showed an accelerated increase over their control level.
      Chlorfluazuron affected Tn5B1-4 and Sf-21 cells, with >=1.8-fold decreases in the
      ratio of cellular N-acetylglucosamine (GlcNAc) level and protein content and
      >=1.5-fold increases in the mitotic index and G2 /M-phase arrest. Neither Hek293
      nor HepG2 cells contained GlcNAc, and chlorfluazuron had no significant effects
      on the cell cycle and mitotic index of Hek293 and HepG2 cells. In conclusion, the
      differences between human and lepidopteran cell lines in the characteristic
      GlcNAc content, G2 /M arrest in the cycle progress, and mitotic index of cells in
      response to chlorfluazuron may contribute to the selective toxicity of
      chlorfluazuron to lepidopteran cells.

PMID- 25753781
TI  - Neural reactivity to visual food stimuli is reduced in some areas of the brain
      during evening hours compared to morning hours: an fMRI study in women.
AB  - The extent that neural responsiveness to visual food stimuli is influenced by
      time of day is not well examined. Using a crossover design, 15 healthy women were
      scanned using fMRI while presented with low- and high-energy pictures of food,
      once in the morning (6:30-8:30 am) and once in the evening (5:00-7:00 pm). Diets
      were identical on both days of the fMRI scans and were verified using weighed
      food records. Visual analog scales were used to record subjective perception of
      hunger and preoccupation with food prior to each fMRI scan. Six areas of the
      brain showed lower activation in the evening to both high- and low-energy foods,
      including structures in reward pathways (P < 0.05). Nine brain regions showed
      significantly higher activation for high-energy foods compared to low-energy
      foods (P < 0.05). High-energy food stimuli tended to produce greater fMRI
      responses than low-energy food stimuli in specific areas of the brain, regardless
      of time of day. However, evening scans showed a lower response to both low- and
      high-energy food pictures in some areas of the brain. Subjectively, participants
      reported no difference in hunger by time of day (F = 1.84, P = 0.19), but
      reported they could eat more (F = 4.83, P = 0.04) and were more preoccupied with
      thoughts of food (F = 5.51, P = 0.03) in the evening compared to the morning.
      These data underscore the role that time of day may have on neural responses to
      food stimuli. These results may also have clinical implications for fMRI
      measurement in order to prevent a time of day bias.

PMID- 25753783
TI  - pi-Extended indenofluorenes.
AB  - A series of pi-extended aromatic indenofluorene (IF) analogues with naphthalene
      and anthracene cores have been synthesized through acid-catalyzed intramolecular
      cyclization. The regioselectivity of the reaction is controlled by a combination
      of steric and electronic factors and in some cases several possible regioisomers
      have resulted from the same precursor. The effects of ring connectivity on the
      optoelectronic properties were investigated by DFT calculations,
      absorption/emission spectroscopy, cyclic voltammetry, and spectroelectrochemical
      studies. All regioisomers exhibited a redshift of their absorption/emission bands
      relative to the parent IF analogues, but the magnitude of this shift and other
      optoelectronic properties (luminescence quantum yield, etc.) depends on the ring
      connectivity in a less obvious manner. 

PMID- 25753782
TI  - In vivo classification of colorectal neoplasia using high-resolution
      microendoscopy: Improvement with experience.
AB  - BACKGROUND AND AIMS: High-resolution microendoscopy (HRME) is a novel, low-cost
      "optical biopsy" technology that allows for subcellular imaging. The study aim
      was to evaluate the learning curve of HRME for the differentiation of neoplastic
      from non-neoplastic colorectal polyps. METHODS: In a prospective cohort fashion,
      a total of 162 polyps from 97 patients at a single tertiary care center were
      imaged by HRME and classified in real time as neoplastic (adenomatous, cancer) or
      non-neoplastic (normal, hyperplastic, inflammatory). Histopathology was the gold
      standard for comparison. Diagnostic accuracy was examined at three intervals over
      time throughout the study; the initial interval included the first 40 polyps, the
      middle interval included the next 40 polyps examined, and the final interval
      included the last 82 polyps examined. RESULTS: Sensitivity increased
      significantly from the initial interval (50%) to the middle interval (94%, P =
      0.02) and the last interval (97%, P = 0.01). Similarly, specificity was 69% for
      the initial interval but increased to 92% (P = 0.07) in the middle interval and
      96% (P = 0.02) in the last interval. Overall accuracy was 63% for the initial
      interval and then improved to 93% (P = 0.003) in the middle interval and 96% (P =
      0.0007) in the last interval. CONCLUSIONS: In conclusion, this in vivo study
      demonstrates that an endoscopist without prior colon HRME experience can achieve
      greater than 90% accuracy for identifying neoplastic colorectal polyps after 40
      polyps imaged. HRME is a promising modality to complement white light endoscopy
      in differentiating neoplastic from non-neoplastic colorectal polyps.

PMID- 25753784
TI  - Systemic sarcoidosis revealed by sarcoidal granulomas on tattoo.

PMID- 25753785
TI  - Platelet function analyser (PFA-100) results and von Willebrand factor
      deficiency: a 16-year 'real-world' experience.
AB  - The platelet function analyser (PFA-100) is a biological tool designed to explore
      primary haemostasis. This system has thus been widely demonstrated as reliable in
      detecting von Willebrand factor (VWF) deficiency. However, most studies were
      based on patients benefitting from regular medical care and accurate diagnosis,
      and it would seem probable that the results were somewhat optimistic, and do not
      reflect its performances in 'real-world' situations. We have chosen to study the
      reliability of PFA-100 for screening VWF ristocetin cofactor (VWF:RCo)
      deficiency. We retrospectively analysed the results (n = 6431) of 4027 patients
      referred to our centre between October 1997 and June 2013 and in whom PFA-Epi,
      PFA-ADP, and VWF:RCo activity had been evaluated. We studied the influence of
      blood group on the results and the performances of each method in a subgroup of
      213 patients with genetically confirmed von Willebrand disease. We have shown
      that the PFA-100 system, in our experience, constitutes an excellent screening
      test for detecting VWF:RCo deficiency, whatever the clinical situation, in 'real
      world' conditions. The negative predictive value (NPV), the positive predictive
      value, the sensitivity and the specificity were respectively: 0.98, 0.51, 0.98
      and 0.40. When values adjusted for blood group are used, NPV and sensitivity are
      inferior to those using normal values which have not been adjusted for blood
      group. We have shown the PFA-100 method to be more efficient in screening for VWF
      deficiency than the VWF:RCo technique. 

PMID- 25753786
TI  - The implications of de novo coding mutations in simplex autism families.

PMID- 25753788
TI  - Exploring the determinants of secular decreases in dental caries among Korean
      children.
AB  - OBJECTIVE: The aim of this study was to determine the contributions of sealant
      and water fluoridation to the time trends in dental caries from 2003 to 2010.
      MATERIALS AND METHODS: Data were from three waves of the Korean National Oral
      Health Surveys between 2003 and 2010, including a total of 23 059 children (11
      889 boys and 11 170 girls) aged 8, 10, and 12 years. The impacts of sealant and
      water fluoridation on dental caries were obtained by logistic regression for each
      age group of children. The contributions of sealant and water fluoridation to the
      time trends in the prevalence of dental caries were examined by a series of
      logistic regression models, and changes in the adjusted odds ratios for each
      survey year were also calculated. RESULTS: Over the past 7 years, the prevalence
      of dental caries decreased dramatically. Although sealant had a significant
      impact on dental caries in each survey year, remarkable decreases in dental
      caries from 2003 to 2010 were not explained by the secular changes in the dental
      sealant or water fluoridation factor. CONCLUSION: We observed important
      population declines in dental caries in Korea in children aged 8-12 years;
      however, the likely causes for these secular trends remain to be determined.

PMID- 25753789
TI  - A national cross-sectional study of community nurses and social workers knowledge
      of self-neglect.
AB  - BACKGROUND: self-neglect (SN) is a global health and social problem affecting
      societies, which is largely hidden, under-reported and underresearched. Community
      nurses (CNs) and social workers (SWs) need to be knowledgeable about SN.
      OBJECTIVE: to determine CNs and SWs sources and level of SN knowledge. METHODS:
      quantitative, descriptive and cross-sectional. SUBJECTS: CNs and SWs working in
      the community with older people at risk of SN. SETTINGS: participants were
      recruited from four Health Service Executive (HSE) areas in Ireland. INSTRUMENT:
      a questionnaire was developed to elicit levels and sources of SN knowledge. A
      postal survey was used. RESULTS: of the 566 questionnaires posted, 339 responded
      (Nurses (N) N = 305; SWs N = 34), a 60% response. SWs had statistically higher
      knowledge scores (P = 0.002), and difference in average scores between CNs and
      SWs was statistically significant (P = 0.037). There was a statistically
      significant difference between practice and personal experience (P = 0.44), and
      use of literature/books (P = 0.037) between CNs and SWs, with SWs using both
      sources more. Higher knowledge scores were significantly associated with number
      of SN cases, higher education and gender. CONCLUSION: there is a need for
      interdisciplinary training on SN.

PMID- 25753790
TI  - Greater progression of athletic performance in older Masters athletes.
AB  - BACKGROUND: The number of new world records has decreased substantially in most
      athletic events in recent years. There has been enormous growth in participation
      at Masters events, and older athletes have been competing at the highest levels
      with much younger athletes. However, the progression of athletic performance over
      time has not been well investigated in Masters athletes. OBJECTIVE AND METHODS:
      To determine whether older Masters athletes improved athletic performance over
      time, running and swimming times from 1975 to 2013 were collected biennially. The
      running event of 100 m was chosen specifically, as it is one of the most popular
      track and field events that would have attracted a large number of competitors.
      The middle distance of 400 m as well as 100 m freestyle swimming were also
      examined to determine whether the results in 100 m sprint event can be confirmed
      in other events. RESULTS: The improvements in fastest 100 m running times over
      time were not significant. However, all the Masters age-group records improved
      significantly over time. The slopes of improvements over the years were
      progressively greater at older age groups with the greatest progression observed
      at oldest age groups of 75-79 years examined. The general trends were similar for
      400 m middle-distance running and 100 m freestyle swimming. CONCLUSIONS: While
      younger athletes' performance has stagnated, Masters athletes improved their
      athletic performance significantly and progressively over the years. The
      magnitude of improvements was greater in older age groups gradually closing the
      gap in athletic performance between younger and older participants.

PMID- 25753793
TI  - Comings and goings.

PMID- 25753787
TI  - Ubiquitination in the antiviral immune response.
AB  - Ubiquitination has long been known to regulate fundamental cellular processes
      through the induction of proteasomal degradation of target proteins. More
      recently, 'atypical' non-degradative types of polyubiquitin chains have been
      appreciated as important regulatory moieties by modulating the activity or
      subcellular localization of key signaling proteins. Intriguingly, many of these
      non-degradative types of ubiquitination regulate the innate sensing pathways
      initiated by pattern recognition receptors (PRRs), ultimately coordinating an
      effective antiviral immune response. Here we discuss recent advances in
      understanding the functional roles of degradative and atypical types of
      ubiquitination in innate immunity to viral infections, with a specific focus on
      the signaling pathways triggered by RIG-I-like receptors, Toll-like receptors,
      and the intracellular viral DNA sensor cGAS. 

PMID- 25753794
TI  - Greenberg comes down squarely on the side that language creates the object of
      interest. Introduction.

PMID- 25753795
TI  - Slicing the psychoanalytic pie: or, shall we bake a new one? Commentary on
      Greenberg.

PMID- 25753796
TI  - Psychoanalytic theories as efforts to grasp the true (not fictional) nature of
      human reality: commentary on Greenberg.

PMID- 25753797
TI  - Action and the analyst's responsibility: commentary on Greenberg.

PMID- 25753798
TI  - Response to commentaries.

PMID- 25753799
TI  - Introduction to the APsaA University Forums.

PMID- 25753800
TI  - Henry James's the portrait of a lady.

PMID- 25753801
TI  - [The discrete and the continuous in freud's "remembering, repeating and working
      through"].

PMID- 25753802
TI  - Goldberg's "On understanding understanding".

PMID- 25753803
TI  - Arnold Goldberg responds.

PMID- 25753804
TI  - Science-in-brief: The 9th Meeting of the International Conference on Equine
      Exercise Physiology 2014. Biochemistry, nutrition and cardiorespiratory function
      of athletic horses.

PMID- 25753805
TI  - Interarm systolic blood pressure as a predictor of cardiovascular events in
      patients with chronic kidney disease.
AB  - BACKGROUND: Increased interarm systolic blood pressure difference (IASBPD) is
      associated with mortality and cardiovascular (CV) events both in the general
      population and in patients at high CV risk. The aim of the present study was to
      assess the value of IASBPD >= 10 mmHg for predicting CV events in patients with
      chronic kidney disease (CKD). METHODS: The study sample comprised 652 patients
      with CKD (age 67 +/- 15 years, 58.1% men). Follow-up was 19 +/- 5 months. We
      recorded increased IASBPD and related factors and assessed the predictive value
      of this variable for CV events. RESULTS: We recorded diabetes mellitus in 136
      patients (20.8%), history of CV disease in 213 (32.6%) and dyslipidaemia in 327
      (50.1%). The mean glomerular filtration rate was 45.9 +/- 18.9 mL/min/1.73 m(2),
      and the median albumin/creatinine ratio was 26(0-151) mg/g. IASBPD was >=10 mmHg
      in 184 patients (28.1%). The factors associated with IASBPD >=10 mmHg were age,
      systolic blood pressure levels, history of congestive heart failure, lower levels
      of high-density lipid cholesterol and higher use of hypertensive drugs. Fifty
      eight patients (8.5%) developed a CV event during the follow-up. IASBPD >=10 mmHg
      [HR, 1.802, 95%CI (1.054-3.079); P = 0.031] was an independent predictor of CV
      events. CONCLUSIONS: Increased IASBPD is an independent predictor of CV events in
      CKD patients.

PMID- 25753806
TI  - B-cell therapy in antineutrophil cytoplasmic antibody-associated vasculitis.
AB  - Until recently, standard of care for patients with generalized or severe
      antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) has
      consisted of an induction regimen with cyclophosphamide (CYC) and corticosteroids
      followed by maintenance treatment with azathioprine. This regimen is associated
      with significant toxicity resulting in considerable morbidity and mortality
      whereas relapses are still not infrequent. In two controlled trials, the
      Rituximab in ANCA-associated Vasculitis study (RAVE) and the RITUXVAS trial of
      the European Vasculitis Study Group (EUVAS), rituximab (RTX) proved non-inferior
      to CYC for induction of remission. In addition, outcome at 18 months for the RAVE
      trial and 12 months for the RITUXVAS trial showed that RTX without maintenance
      treatment was as efficacious as CYC followed by azathioprine maintenance. To
      prevent relapses, which occur particularly in patients positive for PR3-ANCA, 500
      mg RTX given every 6 months was shown to be superior to azathioprine in a French
      study. Thus, RTX is a new and promising therapeutic armamentarium for AAV
      although long-term safety has still to be established. 

PMID- 25753807
TI  - Pop-out in visual search of moving targets in the archer fish.
AB  - Pop-out in visual search reflects the capacity of observers to rapidly detect
      visual targets independent of the number of distracting objects in the
      background. Although it may be beneficial to most animals, pop-out behaviour has
      been observed only in mammals, where neural correlates are found in primary
      visual cortex as contextually modulated neurons that encode aspects of saliency.
      Here we show that archer fish can also utilize this important search mechanism by
      exhibiting pop-out of moving targets. We explore neural correlates of this
      behaviour and report the presence of contextually modulated neurons in the optic
      tectum that may constitute the neural substrate for a saliency map. Furthermore,
      we find that both behaving fish and neural responses exhibit additive responses
      to multiple visual features. These findings suggest that similar neural
      computations underlie pop-out behaviour in mammals and fish, and that pop-out may
      be a universal search mechanism across all vertebrates. 

PMID- 25753808
TI  - Evaluation of muscle and fat loss as diagnostic criteria for malnutrition.
AB  - According to the American Society for Parenteral and Enteral Nutrition and
      Academy of Nutrition and Dietetics criteria, the diagnosis of malnutrition
      includes an evaluation of muscle and fat. The role of inflammation not only
      enhances the catabolism of muscle and fat loss but also interferes with
      anabolism. Dietitians and other nutrition professionals need to understand
      techniques to appropriately identify losses of muscle and fat to incorporate them
      into a malnutrition diagnosis. Proper training is imperative to correctly
      identify muscle and fat wasting in a consistent and reliable manner. Nutrition
      clinicians should begin incorporating these practices into patient assessments
      and care plans. The application of these techniques and assessment tools is
      challenging and continues to be a work in progress. Various scenarios do not
      allow for clearly defined methods that would lead to a reliable conclusion for
      diagnosing malnutrition indicating the need for further research. 

PMID- 25753810
TI  - Alleles of newly identified barley gene HvPARP3 exhibit changes in efficiency of
      DNA repair.
AB  - Genome integrity is constantly challenged by endo- and exogenous DNA-damaging
      factors. The influence of genotoxic agents causes an accumulation of DNA lesions,
      which if not repaired, become mutations that can cause various abnormalities in a
      cell metabolism. The main pathway of DSB repair, which is based on non-homologous
      recombination, is canonical non-homologous end joining (C-NHEJ). It has been
      shown that this mechanism is highly conserved in both Pro- and Eukaryotes. The
      mechanisms that underlie DSB repair through C-NHEJ have mainly been investigated
      in mammalian systems, and therefore our knowledge about this process is much more
      limited as far as plants, and crop plants in particular, are concerned. Recent
      studies have demonstrated that PARP3 is an important response factor to the
      presence of DSB in a genome. The aims of this study were to identify the sequence
      of the barley PARP3 gene, to perform a mutational analysis of the sequence that
      was identified using the TILLING (Targeting Induced Local Lesions IN Genomes)
      method and to phenotype the mutants that were identified through their exposure
      to mutagenic treatment with the DSB-inducing chemical--bleomycin. A functional
      analysis led to the identification of a series of parp3 alleles. The mutants were
      characterized using several different approaches, including quantifying the DSB
      and gammaH2AX foci, which validated the function of the HvPARP3 gene in DSB
      repair in barley. The potential involvement of the HvPARP3 gene in the regulation
      of telomere length in barley was also analyzed.

PMID- 25753809
TI  - Redundancy in ribonucleotide excision repair: Competition, compensation, and
      cooperation.
AB  - The survival of all living organisms is determined by their ability to reproduce,
      which in turn depends on accurate duplication of chromosomal DNA. In order to
      ensure the integrity of genome duplication, DNA polymerases are equipped with
      stringent mechanisms by which they select and insert correctly paired nucleotides
      with a deoxyribose sugar ring. However, this process is never 100% accurate. To
      fix occasional mistakes, cells have evolved highly sophisticated and often
      redundant mechanisms. A good example is mismatch repair (MMR), which corrects the
      majority of mispaired bases and which has been extensively studied for many
      years. On the contrary, pathways leading to the replacement of nucleotides with
      an incorrect sugar that is embedded in chromosomal DNA have only recently
      attracted significant attention. This review describes progress made during the
      last few years in understanding such pathways in both prokaryotes and eukaryotes.
      Genetic studies in Escherichia coli and Saccharomyces cerevisiae demonstrated
      that MMR has the capacity to replace errant ribonucleotides, but only when the
      base is mispaired. In contrast, the major evolutionarily conserved ribonucleotide
      repair pathway initiated by the ribonuclease activity of type 2 Rnase H has broad
      specificity. In yeast, this pathway also requires the concerted action of Fen1
      and pol delta, while in bacteria it can be successfully completed by DNA
      polymerase I. Besides these main players, all organisms contain alternative
      enzymes able to accomplish the same tasks, although with differing efficiency and
      fidelity. Studies in bacteria have very recently demonstrated that isolated rNMPs
      can be removed from genomic DNA by error-free nucleotide excision repair (NER),
      while studies in yeast suggest the involvement of topoisomerase 1 in alternative
      mutagenic ribonucleotide processing. This review summarizes the most recent
      progress in understanding the ribonucleotide repair mechanisms in prokaryotes and
      eukaryotes. 

PMID- 25753811
TI  - DNA polymerase 3'->5' exonuclease activity: Different roles of the beta hairpin
      structure in family-B DNA polymerases.
AB  - Proofreading by the bacteriophage T4 and RB69 DNA polymerases requires a beta
      hairpin structure that resides in the exonuclease domain. Genetic, biochemical
      and structural studies demonstrate that the phage beta hairpin acts as a wedge to
      separate the primer-end from the template strand in exonuclease complexes. Single
      amino acid substitutions in the tip of the hairpin or deletion of the hairpin
      prevent proofreading and create "mutator" DNA polymerases. There is little known,
      however, about the function of similar hairpin structures in other family B DNA
      polymerases. We present mutational analysis of the yeast (Saccharomyces
      cerevisiae) DNA polymerase delta hairpin. Deletion of the DNA polymerase delta
      hairpin (hpDelta) did not significantly reduce DNA replication fidelity; thus,
      the beta hairpin structure in yeast DNA polymerase delta is not essential for
      proofreading. However, replication efficiency was reduced as indicated by a slow
      growth phenotype. In contrast, the G447D amino acid substitution in the tip of
      the hairpin increased frameshift mutations and sensitivity to hydroxyurea (HU). A
      chimeric yeast DNA polymerase delta was constructed in which the T4 DNA
      polymerase hairpin (T4hp) replaced the yeast DNA polymerase delta hairpin; a
      strong increase in frameshift mutations was observed and the mutant strain was
      sensitive to HU and to the pyrophosphate analog, phosphonoacetic acid (PAA). But
      all phenotypes - slow growth, HU-sensitivity, PAA-sensitivity, and reduced
      fidelity, were observed only in the absence of mismatch repair (MMR), which
      implicates a role for MMR in mediating DNA polymerase delta replication problems.
      In comparison, another family B DNA polymerase, DNA polymerase E, has only an
      atrophied hairpin with no apparent function. Thus, while family B DNA polymerases
      share conserved motifs and general structural features, the beta hairpin has
      evolved to meet specific needs. 

PMID- 25753812
TI  - Effect of storage temperature in a Cambodian field setting on the fatty acid
      composition in whole blood.
AB  - Fatty acid analysis requires standardized collection and storage of samples,
      which can be a challenge under field conditions. This study describes the effect
      of storage temperature on fatty acid composition in two sets of whole blood
      samples collected from 66 children in a rural area in Cambodia. The samples were
      stored with butylated hydroxytoluene at -20  degrees C and -80  degrees C and the
      latter required extra transfers due to storage facility limitation. Fatty acid
      composition was analyzed by high-throughput gas-chromatography and evaluated by
      paired t-tests and Bland-Altman plots. Total amounts of fat in -20  degrees C and
      -80  degrees C samples did not differ, but there was relatively more highly
      unsaturated fatty acids (15.8 +/- 2.7 vs. 14.4 +/- 2.5%, p < 0.001) and a lower n
      6/n-3 ratio (6.4 +/- 1.4 vs. 6.9 +/- 1.4, p < 0.001) in the -20  degrees C
      samples. Our results indicate that the importance of storage temperature should
      be evaluated in the context of storage facility availability and risk of
      temperature fluctuations during transport.

PMID- 25753813
TI  - Electron-phonon coupling and its implication for the superconducting topological
      insulators.
AB  - The recent observation of superconductivity in doped topological insulators has
      sparked a flurry of interest due to the prospect of realizing the long-sought
      topological superconductors. Yet the understanding of underlying pairing
      mechanism in these systems is far from complete. Here we investigate this problem
      by providing robust first-principles calculations of the role of electron-phonon
      coupling for the superconducting pairing in the prime candidate CuxBi2Se3. Our
      results show that electron-phonon scattering process in this system is dominated
      by zone center and boundary optical modes, with coexistence of phonon stiffening
      and softening. While the calculated electron-phonon coupling constant lambda
      suggests that Tc from electron-phonon coupling is 2 orders smaller than the ones
      reported on bulk inhomogeneous samples, suggesting that superconductivity may not
      come from pure electron-phonon coupling. We discuss the possible enhancement of
      superconducting transition temperature by local inhomogeneity introduced by
      doping. 

PMID- 25753814
TI  - Comparison of the cryoprotective solutions based on human albumin vs. autologous
      plasma: its effect on cell recovery, clonogenic potential of peripheral blood
      hematopoietic progenitor cells and engraftment after autologous transplantation.
AB  - BACKGROUND AND OBJECTIVES: Cryopreservation of peripheral blood hematopoietic
      progenitor/stem cells (PBPCs) requires the addition of cryoprotectant such as
      DMSO, often prediluted using human serum albumin solution (HSAS). The goal of our
      study was to verify whether the HSAS may be replaced by autologous plasma (AP)
      without negative impact on PBPCs quality and engraftment. AP usage is less
      expensive and allows performing cell preparation in a 'closed system', and hence
      to reduce the risk of product contamination. MATERIALS AND METHODS: Peripheral
      blood progenitor cells from 18 patients were divided into two aliquots (500 MUl)
      placed in separate vials, each containing 7.5% DMSO prediluted with 5% HSAS or
      AP. Post-thaw cell recovery and clonogenic potential was evaluated. During
      clinical part of the study, the impact of both cryoprotective solution on
      hematopoietic engraftment was evaluated in two cohorts (n = 26) matched for
      diagnosis, age and the number of transplanted CD34+ cells. RESULTS: The median
      recovery of nucleated cells and the number of colony-forming units did not differ
      between tested cryoprotective mixtures. For AP mixture, neither total protein nor
      albumin concentration of plasma correlated with cell recovery and clonogenic
      potential of the PBPCs after cryopreservation. In clinical evaluation, the median
      time to leucocyte recovery and reconstitution of neutrophils was comparable in
      both groups: 10 days. We did not observe either significant difference with
      regard to the time of platelet recovery (median: 15 days for AP vs. 16 for HSAS;
      P = 0.79). CONCLUSIONS: HSA in cryoprotective mixture may be replaced by AP
      without negative impact on cell recovery, clonogenic potential or engraftment.

PMID- 25753815
TI  - Birth weight and the risk of overweight in young men born at term.
AB  - OBJECTIVE: The aim of this birth cohort study was to determine the relationship
      between birth weight and the risk of overweight in young adulthood. METHODS: Data
      from the Medical Birth Registry of Norway were linked with register data from the
      National Conscript Service. This study used data on the 348,800 males who were
      born at term in single births in Norway during 1967 to 1984, and who were
      examined at the mandatory military conscription (98% were examined the year they
      turned 18 or 19 years of age). Sibling comparisons were conducted in the 11,865
      sibships of two or more full brothers in which at least one brother was
      overweight (body mass index >=25.0 kg/m(2) ) and at least one brother was not
      overweight. RESULTS: When all the men in the study population were compared with
      each other there was a "J"-shaped association between birth weight and the
      adjusted odds of overweight. When the men were compared with their brothers, the
      adjusted odds of overweight increased in an exponential way (linearly in logit)
      over the entire range of the birth weight scale. A within-family difference of
      100 g in birth weight was associated with a within-family difference of 3.5% (99%
      confidence interval: 2.5-4.6) in the odds of overweight. CONCLUSIONS: There is a
      positive within-family association between birth weight and the odds of
      overweight in young Norwegian men born at term.

PMID- 25753816
TI  - The anti-inflammatory effects of resveratrol on human peripheral blood
      mononuclear cells are influenced by a superoxide dismutase 2 gene polymorphism.
AB  - Resveratrol is an molecule that provides both anti-inflammatory and antioxidant
      properties. However, it is unclear whether the basal oxidative state of the cell
      has any influence on the effects of this compound. In humans, a single nucleotide
      polymorphism (SNP) is present in the enzyme manganese superoxide dismutase
      (SOD2), localized in codon 16 (rs4880), which can either be an alanine (A) or
      valine (V). This SNP causes an imbalance in the cellular levels of SOD2, where AA
      and VV-genotypes result in higher or lower enzymatic activity, respectively.
      Furthermore, the VV-genotype has been associated with high levels of inflammatory
      cytokines. Here, we examined the effects of a range of resveratrol concentrations
      on the in vitro activation of human peripheral blood mononuclear cells (PBMCs)
      carrying different Ala16Val-SOD2 genotypes. Cell proliferation, several oxidative
      biomarkers and cytokines (IL-1beta, IL-6, TNFalpha, Iggamma and IL-10) were
      analyzed. In addition, the effects of resveratrol on the expression of the sirt1
      gene were evaluated by qRT-PCR. After 24 h exposure to resveratrol, A-genotype
      PBMCs displayed a decrease in cell proliferation, whilst VV-cells contrasted; At
      10 uM resveratrol, there was a significant decrease in the production of
      inflammatory cytokines in A-allele cells; however, VV-cells generally displayed a
      subtle decrease in these, except for TNFalpha, which was not affected. In all
      SOD2 genotypes cells exposed to resveratrol resulted in an upregulation of Sirt1
      levels. Together, these results suggest that the effect of resveratrol on human
      PBMC activation is not universal and is dependent on the Ala16Val-SOD2 SNP. 

PMID- 25753818
TI  - Negative urgency and emotion regulation strategy use: Associations with displaced
      aggression.
AB  - The numerous public health consequences of interpersonal aggression highlight the
      necessity of a comprehensive understanding of factors influencing its
      perpetration. This study examined direct and interactive associations between
      negative urgency and emotion regulation strategy use in predicting displaced
      aggression under conditions of negative mood. Participants were 197 male and
      female undergraduate students who were randomly assigned to employ either
      cognitive reappraisal or expressive suppression in response to a negative mood
      induction. Immediately afterwards, participants engaged in an analog displaced
      aggression task. Results revealed direct, positive associations between negative
      urgency and aggression. In addition, the use of suppression was associated with
      greater aggression than was the use of reappraisal alone. Counter to the
      hypothesis, there were no interactive effects between negative urgency and
      emotion regulation strategy use in predicting aggression. Findings suggest
      reducing negative urgency and use of suppression as potential intervention
      targets for individuals who engage in aggressive behavior.

PMID- 25753817
TI  - Multipotent caudal neural progenitors derived from human pluripotent stem cells
      that give rise to lineages of the central and peripheral nervous system.
AB  - The caudal neural plate is a distinct region of the embryo that gives rise to
      major progenitor lineages of the developing central and peripheral nervous
      system, including neural crest and floor plate cells. We show that dual
      inhibition of the glycogen synthase kinase 3beta and activin/nodal pathways by
      small molecules differentiate human pluripotent stem cells (hPSCs) directly into
      a preneuroepithelial progenitor population we named "caudal neural progenitors"
      (CNPs). CNPs coexpress caudal neural plate and mesoderm markers, and, share high
      similarities to embryonic caudal neural plate cells in their lineage
      differentiation potential. Exposure of CNPs to BMP2/4, sonic hedgehog, or FGF2
      signaling efficiently directs their fate to neural crest/roof plate cells, floor
      plate cells, and caudally specified neuroepithelial cells, respectively. Neural
      crest derived from CNPs differentiated to neural crest derivatives and
      demonstrated extensive migratory properties in vivo. Importantly, we also
      determined the key extrinsic factors specifying CNPs from human embryonic stem
      cell include FGF8, canonical WNT, and IGF1. Our studies are the first to identify
      a multipotent neural progenitor derived from hPSCs, that is the precursor for
      major neural lineages of the embryonic caudal neural tube.

PMID- 25753819
TI  - Synthesis and characterization of ion-imprinted resin for selective removal of
      UO2 (II) ions from aqueous medium.
AB  - In this work, uranyl ion-imprinted resin based on 2-(((4
      hydroxyphenyl)amino)methyl)phenol was synthesized by condensation polymerization
      of its uranyl complex in presence of resorcinol and formaldehyde cross-linkers.
      Numerous instrumental techniques including elemental analysis, Fourier transform
      infrared spectroscopy, ultraviolet, (1) H along with (13) C nuclear magnetic
      resonance spectroscopy have been employed for complete characterization of the
      synthesized ligand and its uranyl complex. Additionally, the obtained ion
      imprinted and non-imprinted resins were investigated using scanning electron
      microscope and Fourier transform infrared spectroscopy. The effects of various
      essential parameters such as pH, temperature and contact time on removal of
      uranyl ions have been examined, and the results indicated that the obtained resin
      exhibited the optimum activity at pH 5. Furthermore, the adsorption process was
      spontaneous at all studied temperatures and followed the second-order kinetics
      model. Also, Langmuir adsorption isotherm exhibited the best fit with the
      experimental results with maximum adsorption capacity 139.3 mg/g. Moreover, the
      selectivity studies revealed that the ion-imprinted resin exhibited an obvious
      affinity toward the uranyl ions in presence of other metal ions compared with the
      non-imprinted resin.

PMID- 25753820
TI  - Obeticholic acid and resveratrol in nonalcoholic fatty liver disease: all that is
      gold does not glitter, not all those who wander are lost.

PMID- 25753821
TI  - B-Cells induce regulatory T cells through TGF-beta/IDO production in A CTLA-4
      dependent manner.
AB  - A number of studies have suggested that B cell mediated-regulation contributes to
      the establishment of immunological tolerance. However, the precise mechanisms by
      which regulatory B cells establish and maintain tolerance in humans remain to be
      determined. The objective of the current study is to understand the cellular and
      molecular bases of B-cell regulatory functions in humans. To describe the
      mechanisms regulating the functional plasticity of regulatory B cells, we used an
      in vitro co-culture model based on autologous mixed lymphocyte cultures involving
      freshly isolated B and T cells. The results show that activated B cells regulate
      T cell proliferation through producing transforming growth factor (TGF)-beta and
      indoleamine 2,3-dioxygenase (IDO). The production of TGF-beta and IDO leads to
      the induction of not only "natural" regulatory T cells but also of TGF-beta
      producing CD4(+) T cells and IL-10-producing regulatory T cells. Furthermore, we
      evidenced for the first time that CTLA-4 induces B-cells to produce IDO and to
      become effective induced regulatory B cells (iBregs). This study emphasizes a
      novel regulatory axis and open news insights in how to manage regulatory B cell
      functions in autoimmunity. 

PMID- 25753822
TI  - Integrity testing of PlanovaTM BioEX virus removal filters used in the
      manufacture of biological products.
AB  - Confirmation of virus filter integrity is crucial for ensuring the safety of
      biological products. Two main types of virus filter defects may produce
      inconsistent and undesirable performance in virus removal: improper pore-size
      distribution across the membrane; and specific damage, such as tears, broken
      fibers, or pinholes. Two integrity tests are performed on each individual filter
      manufactured by Asahi Kasei Medical to ensure the absence of these defects prior
      to shipment. In this study, we verified that typical usage of PlanovaTM BioEX
      filters would not improperly shift the pore-size distribution. Damage occurring
      during shipment and use (e.g., broken fibers or pinholes) can be detected by end
      users with sufficient sensitivity using air-water diffusion based leakage tests.
      We prepared and tested filters with model pinhole defects of various sizes to
      develop standard acceptance criteria for the leakage test relative to porcine
      parvovirus infectivity logarithmic reduction values (LRVs). Our results
      demonstrate that pinhole defects at or below a certain size for each effective
      filter surface area have no significant impact on the virus LRV. In conclusion
      the leakage test is sufficiently sensitive to serve as the sole end-user
      integrity test for PlanovaTM BioEX filters, facilitating their use in
      biopharmaceuticals manufacturing. 

PMID- 25753823
TI  - Effect of Steroid Elution on Electrical Performance and Tissue Responses in
      Quadripolar Left Ventricular Cardiac Vein Leads.
AB  - INTRODUCTION: The use of steroid elution (SE) electrode in a cardiac pacing lead
      is known to suppress myocardial inflammation to lower pacing thresholds (PTs). SE
      has been widely utilized on the distal electrode of left ventricular cardiac vein
      (LVCV) leads used in cardiac resynchronization therapy (CRT). However, no paired
      comparison in effect of SE has been studied in proximal electrodes of quadripolar
      LVCV leads. METHODS: We evaluated electrical performance and tissue responses of
      quadripolar LVCV lead electrodes with and without SE in two canine studies with a
      total of 14 canines. Extended bipolar PT and pacing impedance of the LVCV
      electrodes to right ventricle coil were collected via an implantable CRT
      device/programmer or a percutaneous threshold analyzer/pacing analyzer at weeks
      0, 1, 2, 4, 6, 8, and 12. Gross and histopathological examinations of the canines
      were performed at the end of the studies. RESULTS: Our preclinical studies showed
      that SE had significant effects on the long-term pacing performance of
      quadripolar LVCV leads. The SE tip and ring electrodes reduced postimplant PT
      peak and chronic PT, P = 0.038. Histological examination of the perilead tissue
      capsules at 12 weeks showed a reduced thickness for the location of SE
      electrodes. CONCLUSION: SE electrodes in quadripolar LVCV leads lower the PTs,
      and therefore may potentially reduce long-term current drain of CRT systems, thus
      improving the device longevity. These preclinical data serve as rationale to
      include SE on proximal electrodes for the Attain Performa LVCV leads and future
      quadripolar LVCV leads development.

PMID- 25753824
TI  - Antibiotics, Antibiotic Resistance Genes, and Bacterial Community Composition in
      Fresh Water Aquaculture Environment in China.
AB  - Environmental antibiotic resistance has drawn increasing attention due to its
      great threat to human health. In this study, we investigated concentrations of
      antibiotics (tetracyclines, sulfonamides and (fluoro)quinolones) and abundances
      of antibiotic resistance genes (ARGs), including tetracycline resistance genes,
      sulfonamide resistance genes, and plasmid-mediated quinolone resistance genes,
      and analyzed bacterial community composition in aquaculture environment in
      Guangdong, China. The concentrations of sulfametoxydiazine, sulfamethazine,
      sulfamethoxazole, oxytetracycline, chlorotetracycline, doxycycline,
      ciprofloxacin, norfloxacin, and enrofloxacin were as high as 446 MUg kg(-1) and
      98.6 ng L(-1) in sediment and water samples, respectively. The relative
      abundances (ARG copies/16S ribosomal RNA (rRNA) gene copies) of ARGs (sul1, sul2,
      sul3, tetM, tetO, tetW, tetS, tetQ, tetX, tetB/P, qepA, oqxA, oqxB, aac(6')-Ib,
      and qnrS) were as high as 2.8 * 10(-2). The dominant phyla were Proteobacteria,
      Bacteroidetes, and Firmicutes in sediment samples and Proteobacteria,
      Actinobacteria and Bacteroidetes in water samples. The genera associated with
      pathogens were also observed, such as Acinetobacter, Arcobacter, and Clostridium.
      This study comprehensively investigated antibiotics, ARGs, and bacterial
      community composition in aquaculture environment in China. The results indicated
      that fish ponds are reservoirs of ARGs and the presence of potential resistant
      and pathogen-associated taxonomic groups in fish ponds might imply the potential
      risk to human health. 

PMID- 25753825
TI  - Surgical Treatment of Acute Grade III Medial Collateral Ligament Injury Combined
      With Anterior Cruciate Ligament Injury: Anatomic Ligament Repair Versus
      Triangular Ligament Reconstruction.
AB  - PURPOSE: The purpose of this study was to evaluate the clinical results of medial
      collateral ligament (MCL) anatomic ligament repair (ALR) and triangular ligament
      reconstruction (TLR) in treating acute grade III MCL injury with respect to
      imaging and functional results. METHODS: Between January 2009 and October 2011, a
      total of 69 patients with an acute grade III MCL tear combined with an anterior
      cruciate ligament tear were divided into 2 groups: those who underwent ALR and
      those who underwent TLR. Single-bundle anterior cruciate ligament reconstruction
      was also performed in all patients. A radiographic stress-position imaging test
      was performed to evaluate excessive medial opening of the knee. In addition, the
      Slocum test was carried out to assess anteromedial rotatory instability before
      surgery and at follow-up. The subjective symptoms and functional outcomes were
      evaluated preoperatively and postoperatively with International Knee
      Documentation Committee (IKDC) assessment. RESULTS: Sixty-four patients with a
      mean follow-up period of 34 months were included in the final analysis. The
      measurement results for medial opening at the last follow-up appointment
      decreased significantly from the pretreatment measurements and fell within the
      normal range, without a statistically significant difference between the 2 groups
      (P > .05). The overall incidence of anteromedial rotatory instability was reduced
      to 21.9% compared with 62.5% preoperatively. However, the incidence of
      anteromedial rotatory instability in the TLR group (9.4%) decreased significantly
      compared with that in the ALR group (34.4%) (P < .05). All patients' IKDC
      subjective scores significantly improved after surgery. No statistically
      significant difference was found between the 2 groups at the last follow-up (P >
      .05). The comparison of IKDC extension and flexion deficit scores between the 2
      groups showed no significant differences. Eleven patients in the ALR group and 4
      in the TLR group complained of medial knee pain. The comparison between the 2
      groups showed no significant difference (P > .05). CONCLUSIONS: The clinical
      outcomes of this study showed that no major difference existed in the ALR and TLR
      groups based on IKDC scores and medial opening evaluations in the short-term.
      However, TLR offered better rotatory stability than ALR at final follow-up. LEVEL
      OF EVIDENCE: Level II, lesser-quality randomized controlled trial.

PMID- 25753826
TI  - Bioprocessing analysis of Pyrococcus furiosus strains engineered for CO2-based 3
      hydroxypropionate production.
AB  - Metabolically engineered strains of the hyperthermophile Pyrococcus furiosus
      (T(opt) 95-100 degrees C), designed to produce 3-hydroxypropionate (3HP) from
      maltose and CO2 using enzymes from the Metallosphaera sedula (T(opt) 73 degrees
      C) carbon fixation cycle, were examined with respect to the impact of
      heterologous gene expression on metabolic activity, fitness at optimal and sub
      optimal temperatures, gas-liquid mass transfer in gas-intensive bioreactors, and
      potential bottlenecks arising from product formation. Transcriptomic comparisons
      of wild-type P. furiosus, a genetically-tractable, naturally-competent mutant
      (COM1), and COM1-based strains engineered for 3HP production revealed numerous
      differences after being shifted from 95 degrees C to 72 degrees C, where product
      formation catalyzed by the heterologously-produced M. sedula enzymes occurred. At
      72 degrees C, significantly higher levels of metabolic activity and a stress
      response were evident in 3HP-forming strains compared to the non-producing parent
      strain (COM1). Gas-liquid mass transfer limitations were apparent, given that 3HP
      titers and volumetric productivity in stirred bioreactors could be increased over
      10-fold by increased agitation and higher CO2 sparging rates, from 18 mg/L to 276
      mg/L and from 0.7 mg/L/h to 11 mg/L/h, respectively. 3HP formation triggered
      transcription of genes for protein stabilization and turnover, RNA degradation,
      and reactive oxygen species detoxification. The results here support the
      prospects of using thermally diverse sources of pathways and enzymes in
      metabolically engineered strains designed for product formation at sub-optimal
      growth temperatures.

PMID- 25753827
TI  - Synthesis of peptide nucleic acids containing pyridazine derivatives as cytosine
      and thymine analogs, and their duplexes with complementary oligodeoxynucleotides.
AB  - Synthesis of peptide nucleic acids (PNAs) is reported with new pyridazine-type
      nucleobases: 3-aminopyridazine (aPz) and 1-aminophthalazine (aPh) as cytosine
      analogs, and pyridazin-3-one (Pz(O)) and phthalazin-1-one (Ph(O)) as thymine
      analogs. The PNAs having an aPz or a Pz(O) formed duplexes with each
      complementary oligodeoxynucleotide forming a base pair with G or A, respectively,
      as evaluated by using UV melting analyses and circular dichroism (CD) spectra. 

PMID- 25753828
TI  - Brain oxygenation patterns during the execution of tool use demonstration, tool
      use pantomime, and body-part-as-object tool use.
AB  - Divergent findings exist whether left and right hemispheric pre- and postcentral
      cortices contribute to the production of tool use related hand movements. In
      order to clarify the neural substrates of tool use demonstrations with tool in
      hand, tool use pantomimes without tool in hand, and body-part-as-object
      presentations of tool use (BPO) in a naturalistic mode of execution, we applied
      functional Near InfraRed Spectroscopy (fNIRS) in twenty-three right-handed
      participants. Functional NIRS techniques allow for the investigation of brain
      oxygenation during the execution of complex hand movements with an unlimited
      movement range. Brain oxygenation patterns were retrieved from 16 channels of
      measurement above pre- and postcentral cortices of each hemisphere. The results
      showed that tool use demonstration with tool in hand leads to increased
      oxygenation as compared to tool use pantomimes in the left hemispheric
      somatosensory gyrus. Left hand executions of the demonstration of tool use,
      pantomime of tool use, and BPO of tool use led to increased oxygenation in the
      premotor and somatosensory cortices of the left hemisphere as compared to right
      hand executions of either condition. The results indicate that the premotor and
      somatosensory cortices of the left hemisphere constitute relevant brain
      structures for tool related hand movement production when using the left hand,
      whereas the somatosensory cortex of the left hemisphere seems to provide specific
      mental representations when performing tool use demonstrations with the tool in
      hand. 

PMID- 25753829
TI  - Comparison of X-ray powder diffraction and solid-state nuclear magnetic resonance
      in estimating crystalline fraction of tacrolimus in sustained-release amorphous
      solid dispersion and development of discriminating dissolution method.
AB  - The focus of present investigation was to explore X-ray powder diffraction (XRPD)
      and solid-state nuclear magnetic resonance (ssNMR) techniques for amorphous and
      crystalline tacrolimus quantification in the sustained-release amorphous solid
      dispersion (ASD), and to propose discriminating dissolution method that can
      detect crystalline drug. The ASD and crystalline physical mixture was mixed in
      various proportions to make sample matrices containing 0%-100% crystalline
      amorphous tacrolimus. Partial-least-square regression and principle component
      regression were applied to the spectral data. Dissolution of the ASD in the US
      FDA recommended dissolution medium with and without surfactant was performed.
      R(2) > 0.99 and slope was close to one for all the models. Root-mean-square of
      prediction, standard error of prediction, and bias were higher in ssNMR-based
      models when compared with XRPD data models. Dissolution of the ASD decreased with
      an increase in the crystalline tacrolimus in the formulations. Furthermore,
      detection of crystalline tacrolimus in the ASD was progressively masked with an
      increase in the surfactant level in the dissolution medium. XRPD and ssNMR can be
      used equally to quantitate the crystalline and amorphous fraction of tacrolimus
      in the ASD with good accuracy; however, ssNMR data collection time is excessively
      long, and minimum surfactant level in the dissolution medium maximizes detection
      of crystalline reversion in the formulation.

PMID- 25753830
TI  - Prediction of the pharmacokinetics and tissue distribution of levofloxacin in
      humans based on an extrapolated PBPK model.
AB  - This study developed a physiologically based pharmacokinetic (PBPK) model in
      intraabdominally infected rats and extrapolated it to humans to predict the
      levofloxacin pharmacokinetics and penetration into tissues. Twelve male rats with
      intraabdominal infections induced by Escherichia coli received a single dose of
      50 mg/kg body weight of levofloxacin. Blood plasma was collected at 5, 10, 20,
      30, 60, 120, 240, 480 and 1440 min after injection, respectively. A PBPK model
      was developed in rats and extrapolated to humans using GastroPlus software. The
      predictions were assessed by comparing predictions and observations. In the
      plasma concentration-versus-time profile of levofloxacin in rats, C max was
      23.570 MUg/ml at 5 min after intravenous injection, and t1/2 was 2.38 h. The
      plasma concentration and kinetics in humans were predicted and validated by the
      observed data. Levofloxacin penetrated and accumulated with high concentrations
      in the heart, liver, kidney, spleen, muscle and skin tissues in humans. The
      predicted tissue-to-plasma concentration ratios in abdominal viscera were between
      1.9 and 2.3. When rat plasma concentrations were known, extrapolation of a PBPK
      model was a method to predict the drug pharmacokinetics and penetration in
      humans. Levofloxacin had good penetration into the liver, kidney and spleen as
      well as other tissues in humans. This pathological model extrapolation may
      provide a reference for the study of antiinfective PK/PD. In our study,
      levofloxacin penetrated well into abdominal organs. Also ADR monitoring should be
      implemented when using levofloxacin. 

PMID- 25753831
TI  - A pharmacokinetic study of patchouli alcohol after a single oral administration
      of patchouli alcohol or patchouli oil in rats.
AB  - Pogostemonis herba is used in traditional Chinese medicine to remove dampness,
      relieve sunstroke, stop vomiting and increase appetite. Patchouli alcohol, an
      ingredient in pogostemonis herba, has the potential to treat inflammation as well
      as bacterial and fungal infections. The essential oil of pogostemonis herba
      (patchouli oil) is commonly given orally in clinical settings; however, no
      pharmacokinetic studies have examined its oral administration. The goal of this
      study was to investigate the pharmacokinetic behavior of patchouli alcohol
      following single-dose oral administration in rats; the influence of other
      patchouli oil components on the pharmacokinetic profile of patchouli alcohol was
      also examined. In this study, a simple and selective GC/MS method was developed
      and validated to measure the level of patchouli alcohol in rat plasma. The study
      revealed that the pharmacokinetics profile was linear in both the patchouli
      alcohol and patchouli oil groups. The C max and AUC0-t of patchouli alcohol were
      greater in all three doses of patchouli alcohol compared to corresponding
      patchouli oil doses. Additionally, the T max values were significantly greater in
      the patchouli oil group. These results suggest that the other ingredients in
      patchouli oil influence the pharmacokinetic behavior of patchouli alcohol during
      its absorption. The results provide a meaningful basis for evaluating the
      clinical application of patchouli oil and patchouli alcohol. 

PMID- 25753832
TI  - Increased levels of plasma glial-derived neurotrophic factor in children with
      attention deficit hyperactivity disorder.
AB  - BACKGROUND: Recent evidence suggests that neurotrophic growth factor systems,
      including brain-derived neurotrophic factor, might be involved in the
      pathophysiology of attention deficit hyperactivity disorder (ADHD). Glial cell
      line-derived neurotrophic factor (GDNF) is from the transforming growth factor
      beta family and is abundantly expressed in the central nervous system, where it
      plays a role in the development and function of hippocampal cells. To date, no
      association studies have been done between ADHD and GDNF. Thus, here we
      investigate the hypothesis that there are differences in plasma GDNF levels
      between children with ADHD and healthy controls. METHODS: Plasma GDNF levels were
      measured in 86 drug-naive children with ADHD and 128 healthy children. The
      severity of ADHD symptoms was determined by scores on the Korean ADHD Rating
      Scale (K-ARS) in patients and healthy controls. RESULTS: The median plasma GDNF
      levels in ADHD patients was 74.0 (IQR: 23.4-280.1) pg/ml versus 24.6 (IQR: 14.5
      87.3) pg/ml in healthy controls; thus the median plasma GDNF levels in ADHD
      patients were significantly higher than in healthy controls (Mann-Whitney U-test,
      P < 0.01). Plasma GDNF levels were correlated positively with K-ARS subscale
      scores (inattention, hyperactivity-impulsivity and total), determined by
      Spearman's correlation test in ADHD patients and healthy controls (r = 0.371, P <
      0.01; r = 0.331, P < 0.01; and r = 0.379, P < 0.01, respectively). CONCLUSIONS:
      These findings suggest increased plasma GDNF levels in untreated ADHD patients.
      In addition, plasma GDNF levels had a significant positive correlation with
      inattention, hyperactivity-impulsivity and K-ARS total scores in ADHD patients
      and healthy controls. Further studies are required to determine the source and
      role of circulating GDNF in ADHD.

PMID- 25753833
TI  - Oral ribavirin for respiratory syncytial virus infection after lung
      transplantation: Efficacy and cost-efficiency.
AB  - BACKGROUND: Respiratory syncytial virus (RSV) causes serious respiratory tract
      infections in lung transplant (LTx) recipients, is associated with development of
      bronchiolitis obliterans syndrome, and has no proven effective therapy. We
      evaluated the efficacy, safety, and cost-effectiveness of oral ribavirin for the
      treatment of RSV infection after LTx. METHODS: Between December 2011 and May
      2014, 52 LTx recipients developed 56 episodes of symptomatic RSV infection, which
      was diagnosed by positive RSV polymerase chain reaction on nasopharyngeal swabs.
      An intravenous (IV) loading dose of ribavirin (33 mg/kg) was given in 52 of 56
      episodes; an equivalent oral loading dose was given in 2 episodes. Oral ribavirin
      (20 mg/kg/day) was given by day 2 in 53 of 56 episodes. Median duration of
      therapy was 8 days (range 6-31 days). RESULTS: Mean forced expiratory volume in 1
      sec decreased from 2.38 +/- 0.78 liters to 2.07 +/- 0.85 liters (p < 0.001) at
      presentation, recovered to 2.26 +/- 0.82 liters at cessation of ribavirin, and
      was maintained at 2.31 +/- 0.81 liters within 3 months. New-onset bronchiolitis
      obliterans syndrome developed in 1 of 38 patients (2.6%) at 3 months. Anemia
      worsened in 23 episodes, and de novo anemia developed in 5 episodes. Mean
      hemoglobin decreased from 118 +/- 16 g/liter to 113 +/- 21 g/liter (p = 0.015).
      There were 4 late deaths. Compared with IV therapy, mean drug cost saving was US
      $6,035 per episode, and mean inpatient bed days was reduced by 6.7 days (p <
      0.001). CONCLUSIONS: To our knowledge, we report the largest series of LTx
      recipients treated with oral ribavirin for RSV. Oral ribavirin appears to be an
      effective, well-tolerated alternative to IV or inhaled ribavirin; provides
      considerable cost savings and reduces length of hospital stay. Potential long
      term benefits in preventing development of chronic lung allograft dysfunction are
      yet to be determined.

PMID- 25753834
TI  - Attributions of Stability, Control and Responsibility: How Parents of Children
      with Intellectual Disabilities View their Child's Problematic Behaviour and Its
      Causes.
AB  - BACKGROUND: Children with intellectual disabilities have high rates of behaviour
      problems. This study explored parents' causal beliefs and attributions for
      general problematic child behaviour in children with different aetiologies of
      intellectual disabilities. MATERIALS AND METHODS: Ten parents of children with
      intellectual disabilities participated in interviews about their child's
      problematic behaviour. RESULTS: Thematic analysis using NVivo revealed that
      parents viewed their child's problematic behaviour not only as caused by the
      child's intellectual disabilities but also by other causes unrelated to the
      intellectual disabilities, as well as by aspects of the social environmental
      context. Some causes were viewed as stable and uncontrollable and others as
      unstable and controllable. In addition, parents showed a strong sense of
      responsibility for child behaviour. CONCLUSIONS: Parents of children with
      intellectual disabilities do not solely interpret their child's problematic
      behaviour through the intellectual disabilities but incorporate the environment
      and causes and attributions that are not related to the intellectual
      disabilities, which may help to promote more effective parenting.

PMID- 25753835
TI  - Comment.

PMID- 25753836
TI  - Gastrointestinal Endoscopy Competency Assessment Tool: reliability and validity
      evidence.
AB  - BACKGROUND: Rigorously developed and validated direct observational assessment
      tools are required to support competency-based colonoscopy training to facilitate
      skill acquisition, optimize learning, and ensure readiness for unsupervised
      practice. OBJECTIVE: To examine reliability and validity evidence of the
      Gastrointestinal Endoscopy Competency Assessment Tool (GiECAT) for colonoscopy
      for use within the clinical setting. DESIGN: Prospective, observational,
      multicenter validation study. Sixty-one endoscopists performing 116 colonoscopies
      were assessed using the GiECAT, which consists of a 7-item global rating scale
      (GRS) and 19-item checklist (CL). A second rater assessed procedures to determine
      interrater reliability by using intraclass correlation coefficients (ICCs).
      Endoscopists' first and second procedure scores were compared to determine test
      retest reliability by using ICCs. Discriminative validity was examined by
      comparing novice, intermediate, and experienced endoscopists' scores. Concurrent
      validity was measured by correlating scores with colonoscopy experience, cecal
      and terminal ileal intubation rates, and physician global assessment. SETTING: A
      total of 116 colonoscopies performed by 33 novice (<50 previous procedures), 18
      intermediate (50-500 previous procedures), and 10 experienced (>1000 previous
      procedures) endoscopists from 6 Canadian hospitals. MAIN OUTCOME MEASUREMENTS:
      Interrater and test-retest reliability, discriminative, and concurrent validity.
      RESULTS: Interrater reliability was high (total: ICC=0.85; GRS: ICC=0.85; CL:
      ICC=0.81). Test-retest reliability was excellent (total: ICC=0.91; GRS: ICC=0.93;
      CL: ICC=0.80). Significant differences in GiECAT scores among novice,
      intermediate, and experienced endoscopists were noted (P<.001). There was a
      significant positive correlation (P<.001) between scores and number of previous
      colonoscopies (total: rho=0.78, GRS: rho=0.80, CL: Spearman's rho=0.71); cecal
      intubation rate (total: rho=0.81, GRS: Spearman's rho=0.82, CL: Spearman's
      rho=0.75); ileal intubation rate (total: Spearman's rho=0.82, GRS: Spearman's
      rho=0.82, CL: Spearman's rho=0.77); and physician global assessment (total:
      Spearman's rho=0.90, GRS: Spearman's rho=0.94, CL: Spearman's rho=0.77).
      LIMITATIONS: Nonblinded assessments. CONCLUSION: This study provides evidence
      supporting the reliability and validity of the GiECAT for use in assessing the
      performance of live colonoscopies in the clinical setting.

PMID- 25753837
TI  - Anatomic ACL reconstruction: rectangular tunnel/bone-patellar tendon-bone or
      triple-bundle/semitendinosus tendon grafting.
AB  - Anatomic ACL reconstruction is the reasonable approach to restore stability
      without loss of motion after ACL tear. To mimic the normal ACL like a ribbon, our
      preferred procedures is the anatomic rectangular tunnel (ART) technique with a
      bone-patellar tendon-bone (BTB) graft or the anatomic triple bundle (ATB)
      procedure with a hamstring (HS) tendon graft. It is important to create tunnel
      apertures inside the attachment areas to lessen the tunnel widening. To identify
      the crescent-shaped ACL femoral attachment area, the upper cartilage margin, the
      posterior cartilage margin and the resident's ridge are used as landmarks. To
      delineate the C-shaped tibial insertion, medial intercondylar ridge, Parson's
      knob and anterior horn of the lateral meniscus are helpful. In ART-BTB procedure
      which is suitable for male patients engaged in contact sports, the parallelepiped
      tunnels with rectangular apertures are made within the femoral and tibial
      attachment areas. In ATB-HS technique which is mainly applied to female athletes
      engaged in non-contact sports including skiing or basketball, 2 femoral and 3
      tibial round tunnels are created inside the attachment areas. These techniques
      make it possible for the grafts to run as the native ACL without impingement to
      the notch or PCL. After femoral fixation with an interference screw or cortical
      fixation devices including Endobutton, the graft is pretensioned in situ by
      repetitive manual pulls at 15-20 degrees  of flexion, monitoring the graft
      tension with tensioners on a tensioning boot installed on the calf. Tibial
      fixation with pullout sutures is achieved using Double Spike Plate and a screw at
      the pre-determined amount of tension of 10-20N. While better outcomes with less
      failure rate are being obtained compared to those in the past, higher graft tear
      rate remains a problem. Improved preventive training may be required to avoid
      secondary ACL injuries. 

PMID- 25753838
TI  - The effect of administration of double stranded MicroRNA-210 on acceleration of
      Achilles tendon healing in a rat model.
AB  - BACKGROUND: Achilles tendons heal slower than other tissues, therefore requiring
      the developmnent of a strategy for accelerating the process. Vascular supply
      plays an important role in primary tendon healing, especially during the early
      healing phase. MicroRNA (miR)-210 has been reported as being crucial for
      angiogenesis, which is a key factor of tissue repair. We report herein that local
      injection of synthetic miR-210 into the injured Achilles tendon of a rat
      accelerated healing of the tendon. METHODS: Achilles tendons were transected and
      repaired via the Kessler suture technique in Sprague-Dawley rats. Then, double
      stranded (ds) miR-210 was injected into the repaired sites. The control group was
      injected with non-functioned dsRNA. At 2, 6 and 12 weeks, histological
      evaluations were performed. At two and six weeks, mechanical testing and
      angiogenesis were evaluated. Gene expression analysis using real-time polymerase
      chain reaction (PCR) and immunohistochemistry were performed at two weeks.
      RESULT: At two and six weeks, regular dense collagen tissue in the miR-210 group
      was observed and the diameter of collagen fiber in the miR-210 group was
      significantly higher than in the control. At two weeks, the ultimate failure load
      was significantly higher than in the control group, and expression of VEGF, FGF2
      and type I collagen was upregulated. Abundant vessels in the miR-210 group were
      observed at two weeks, but there was no significant difference in vessel numbers
      between the two groups at six weeks. At 12 weeks, repaired Achilles tendons in
      the miR-210 group consisted of parallel and dense fibers, whereas wavy and loose
      fibers were still observed in the control group. CONCLUSION: The current study
      showed that single local injection of synthetic miR-210 promotes Achilles tendon
      healing in the early phase.

PMID- 25753839
TI  - Thrombospondin-1 induces differential response in human corneal and conjunctival
      epithelial cells lines under in vitro inflammatory and apoptotic conditions.
AB  - Recently, thrombospondin-1 (TSP-1) has been reported to be critical for
      maintaining a healthy ocular surface. The purpose of the study was to
      characterize the expression of TSP-1 and of its receptors CD36 and CD47 in
      corneal and conjunctival epithelial cells and determine the effect of exogenous
      TSP-1 treatment on these cells, following the induction of inflammation- and
      apoptosis-related changes. The expression of TSP-1, CD36 and CD47 by corneal and
      conjunctival cell lines was firstly characterized by ELISA, immunofluorescence
      analysis, Western blotting and reverse transcription polymerase chain reaction
      (RT-PCR). Benzalkonium chloride (BAC) exposure for 5 or 15 min was used as pro
      inflammatory and pro-apoptotic stimulus for corneal or conjunctival epithelial
      cells, respectively. To analyze inflammation and apoptosis-related changes, IL-6
      and TGF-beta2 secretion determined by ELISA was used as inflammatory markers,
      while activated caspase-3/7 levels and cell viability, determined by CellEventTM
      Caspase-3/7 Green Detection Reagent and XTT cytotoxicity assay, respectively,
      were used as apoptotic markers. Changes in CD36 and CD47 mRNA expression were
      quantified by real time RT-PCR. Corneal epithelial cells secreted and expressed
      higher protein levels of TSP-1 than conjunctival epithelial cells, although TSP-1
      mRNA expression levels were similar and had lower CD36 and CD47, both at protein
      and mRNA levels. Both cell lines responded to exogenous TSP-1 treatment
      increasing CD36 at protein and mRNA levels. Blocking experiments revealed a
      predominance of TSP-1/CD47 rather than TSP-1/CD36 interactions to up-regulate
      CD36 levels in conjunctival epithelial cells, but not in corneal epithelial
      cells. BAC exposure increased IL-6 secretion and caspase-3/7 levels and decreased
      cell viability in both, corneal and conjunctival epithelial cells. Moreover, BAC
      exposure increased latent TGF-beta2 levels in conjunctival epithelial cells.
      Interestingly, CD36 mRNA expression was down-regulated after BAC exposure in both
      cell lines. Exogenous TSP-1 treatment reduced TGF-beta2 up-regulated levels by
      BAC exposure in conjunctival epithelial cells and less pronounced reduced IL-6 in
      BAC-exposed corneal epithelial cells. The effect on CD36 and CD47 regulation was
      less pronounced or even opposite depending on the inflammation- and apoptosis
      related markers tested. Our results show evidence of the capacity of corneal and
      conjunctival epithelial cells to respond to TSP-1 via CD36 or CD47. Experimental
      simulation of inflammation- and apoptosis-related conditions changed the effects
      differentially elicited by TSP-1 on corneal and conjunctival epithelial cells,
      suggesting an unexpected and relevant contribution of TSP-1 on ocular surface
      homeostasis regulation. 

PMID- 25753840
TI  - An acute intraocular pressure challenge to assess retinal ganglion cell injury
      and recovery in the mouse.
AB  - We describe a model of acute intraocular pressure (IOP) elevation in the mouse
      eye that induces reversible loss of inner retinal function associated with
      oxidative stress, glial cell activation and minimal loss of retinal ganglion cell
      (RGC) number. Young healthy mouse eyes recover inner retinal function within 7
      days but more persistent functional loss is seen in older mice. Manipulation of
      diet and exercise further modify RGC recovery demonstrating the utility of this
      injury model for investigating lifestyle and therapeutic interventions. We
      believe that systematic investigation into the characteristics and determinants
      of RGC recovery following an IOP challenge will shed light on processes that
      govern RGC vulnerability in the early stages of glaucoma. 

PMID- 25753841
TI  - The performance of low-cost commercial cloud computing as an alternative in
      computational chemistry.
AB  - The growth of commercial cloud computing (CCC) as a viable means of computational
      infrastructure is largely unexplored for the purposes of quantum chemistry. In
      this work, the PSI4 suite of computational chemistry programs is installed on
      five different types of Amazon World Services CCC platforms. The performance for
      a set of electronically excited state single-point energies is compared between
      these CCC platforms and typical, "in-house" physical machines. Further
      considerations are made for the number of cores or virtual CPUs (vCPUs, for the
      CCC platforms), but no considerations are made for full parallelization of the
      program (even though parallelization of the BLAS library is implemented),
      complete high-performance computing cluster utilization, or steal time. Even with
      this most pessimistic view of the computations, CCC resources are shown to be
      more cost effective for significant numbers of typical quantum chemistry
      computations. Large numbers of large computations are still best utilized by more
      traditional means, but smaller-scale research may be more effectively undertaken
      through CCC services.

PMID- 25753842
TI  - Review of MRI wrist examination since introduction of Medicare item number.
AB  - INTRODUCTION: The Australian Health Department provided extended rebatable
      requesting rights to general practitioners in 2012 for magnetic resonance imaging
      (MRI) examinations in patients less than 16 years of age for a small set of
      clinically appropriate indications. Included item numbers 63522 and 63523
      'referral by a medical practitioner (excluding a specialist and consultant
      physician) for a scan of wrist following radiographic examination where scaphoid
      fracture is suspected'. The aim of this study is to evaluate MRI examinations of
      suspected scaphoid fractures in the paediatric population following the Medicare
      item number introduction. METHODS: Review of 60 consecutive MR wrist examinations
      requested by general practitioners and performed between 30 November 2012 and 16
      July 2014 for a rebatable magnet in a private clinical setting. The indication
      for all studies was to exclude a clinically suspected fractured scaphoid
      following a normal radiograph. All patients were less than 16 years of age at
      time of examination. RESULTS: Sixty examinations were performed; 51 revealed
      pathology (85% of cases) with nine normal examinations (15%). Twenty-nine studies
      revealed one of more fractures involving the carpals, metacarpals or distal
      radius. In total, 41 fractures were identified on MRI examination with 29 carpal
      bone fractures, six distal radius fractures and six metacarpal fractures.
      CONCLUSIONS: The results highlight the sensitivity of MR wrist examination and
      its diagnostic benefit in clinically suspected paediatric scaphoid fractures. In
      addition, it reflects the prudent referral nature of general practitioners.

PMID- 25753843
TI  - Attenuating effects of coenzyme Q10 and amlodipine in ulcerative colitis model in
      rats.
AB  - CONTEXT: Ulcerative colitis is a chronic inflammatory bowel disease. Recent
      studies reported a pivotal role of elevated intracellular calcium in this
      disorder. Coenzyme Q10 (CoQ10) and amlodipine are known to maintain cellular
      energy, decrease intracellular calcium concentration in addition to their
      antioxidant and anti-inflammatory properties. OBJECTIVE: The aim of this study
      was to evaluate the possible protective effects of CoQ10, amlodipine and their
      combination on ulcerative colitis. MATERIALS AND METHODS: Colitis was induced in
      rats by intracolonic injection of 3% acetic acid. CoQ10 (10 mg/kg), amlodipine (3
      mg/kg) and their combination were administered for 8 consecutive days before
      induction of colitis. RESULTS: Our results showed that administration of CoQ10,
      amlodipine and their combination decreased colon tissue malondialdehyde (MDA),
      tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta),
      prostaglandin E2 (PGE2), myeloperoxidase (MPO) and heat shock protein (HSP70)
      levels induced by intracolonic injection of acetic acid and restored many of the
      colon structure in histological examination. On the other hand, they increased
      superoxide dismutase (SOD) activity, adenosine-5'-triphosphate (ATP) and
      interleukin-10 (IL-10) colonic contents. DISCUSSION AND CONCLUSION:
      Administration of either CoQ10 or amlodipine was found to protect against acetic
      acid-induced colitis. Moreover, their combination was more effective than
      individual administration of either of them. The protective effect of CoQ10 and
      amlodipine may be in part via their antioxidant, anti-inflammatory and energy
      restoration properties.

PMID- 25753844
TI  - Anti-asthma potential of crocin and its effect on MAPK signaling pathway in a
      murine model of allergic airway disease.
AB  - CONTEXT: Crocin, a diterpenoid glucoside, has multitudinous activities such as
      anti-inflammation, anti-allergy, anti-oxidation and relaxing smooth muscles.
      OBJECTIVE: In this study, the potential of crocin as an anti-asthma agent was
      investigated in a murine model. MATERIALS AND METHODS: BALB/c mice were
      sensitized and challenged by ovalbumin (OVA) to induce allergic airway
      inflammation, with crocin administered one hour before every OVA challenge.
      Airway hyper-reactivity was evaluated by lung function analysis systems.
      Leukocyte counts in bronchoalveolar lavage fluid (BALF) were measured by a
      hemocytometer and Diff-Quick-stained smears. Lung tissues were stained with
      hematoxylin-eosin, Congo red and methylene blue for histopathological inspection.
      Inflammatory mediators in serum, BALF and lung were measured by ELISA or RT-PCR.
      Effects of crocin on MAPK signaling pathways were investigated by western blot
      analysis. RESULTS: Crocin significantly suppressed airway inflammation and hyper
      reactivity, reduced levels of BALF interleukin (IL-4), IL-5, IL-13 and tryptase,
      lung eosinophil peroxidase and serum OVA-specific IgE, and inhibited the
      expression of lung eotaxin, p-ERK, p-JNK and p-p38 in the OVA-challenged mice.
      CONCLUSIONS: These results demonstrated that the suppression of crocin on airway
      inflammation and hyper-reactivity in a murine model, thus crocin might have a
      great potential to be a candidate for the treatment of asthma.

PMID- 25753845
TI  - Ursolic acid isolated from guava leaves inhibits inflammatory mediators and
      reactive oxygen species in LPS-stimulated macrophages.
AB  - Psidium guajava (guava) leaves have been frequently used for the treatment of
      rheumatism, fever, arthritis and other inflammatory conditions. The purpose of
      this study was to identify major anti-inflammatory compounds from guava leaf
      extract. The methanol extract and its hexane-, dichloromethane-, ethylacetate-, n
      butanol- and water-soluble phases derived from guava leaves were evaluated to
      determine their inhibitory activity on nitric oxide (NO) production by RAW 264.7
      cells stimulated with lipopolysaccharide (LPS). The methanol extract decreased NO
      production in a dose-dependent manner without cytotoxicity at a concentration
      range of 0-100 MUg/mL. The n-butanol soluble phase was the most potent among the
      five soluble phases. Four compounds were isolated by reversed-phase HPLC from the
      n-butanol soluble phase and identified to be avicularin, guaijaverin,
      leucocyanidin and ursolic acid by their NMR spectra. Among these compounds,
      ursolic acid inhibited LPS-induced NO production in a dose-dependent manner
      without cytotoxity at a concentration range of 1-10 uM, but the other three
      compounds had no effect. Ursolic acid also inhibited LPS-induced prostaglandin E2
      production. A western blot analysis showed that ursolic acid decreased the LPS
      stimulated inducible nitric oxide synthase and cyclooxygenase protein levels. In
      addition, ursolic acid suppressed the production of intracellular reactive oxygen
      species in LPS-stimulated RAW 264.7 cells, as measured by flow cytometry. Taken
      together, these results identified ursolic acid as a major anti-inflammatory
      compound in guava leaves.

PMID- 25753846
TI  - Formerly eclamptic women have lower nonpregnant blood pressure compared with
      formerly pre-eclamptic women: a retrospective cohort study.
AB  - OBJECTIVE: To compare nonpregnant blood pressure and circulating metabolic
      factors between formerly pre-eclamptic women who did and did not deteriorate to
      eclampsia. DESIGN: Retrospective observational cohort study. SETTING: Tertiary
      referral centre. POPULATION: Formerly pre-eclamptic women with (n = 88) and
      without (n = 698) superimposed eclampsia. METHODS: Women who experienced pre
      eclampsia with or without superimposed eclampsia during their pregnancy or
      puerperium were tested for possible underlying cardiovascular risk factors at
      least 6 months postpartum. We measured blood pressure and determined
      cardiovascular and metabolic risk markers in a fasting blood sample. Groups were
      compared using Mann-Whitney U test, Spearman's Rho test or Fisher's Exact test
      (odds ratios). MAIN OUTCOME MEASURES: Differences in postpartum blood pressures
      and features of the metabolic syndrome between formerly pre-eclamptic and
      formerly eclamptic women. RESULTS: Formerly pre-eclamptic women who developed
      eclampsia differed from their counterparts without eclampsia by a lower blood
      pressure (P < 0.01) with blood pressure correlating inversely with the likelihood
      of having experienced eclampsia (P < 0.001). In addition, formerly eclamptic
      women had higher circulating C-reactive protein levels than formerly pre
      eclamptic women (P < 0.05). All other circulating metabolic factors were
      comparable. Finally, 40% of all eclamptic cases occurred in the puerperium.
      CONCLUSIONS: Formerly pre-eclamptic women with superimposed eclampsia have lower
      nonpregnant blood pressure compared with their counterparts without neurological
      sequelae with blood pressure negatively correlated to the occurrence of
      eclampsia. As about 40% of all eclamptic cases occur postpartum, routine blood
      pressure monitoring postpartum should be intensified.

PMID- 25753847
TI  - Longitudinal brain volumetric changes and their predictive effects on cognition
      among cognitively asymptomatic patients with Parkinson's disease.
AB  - INTRODUCTION: Existing literature on brain volumetric alterations in patients
      with Parkinson's disease (PD) have mainly focused on gray matter (GM) and are
      largely cross-sectional. Little is known about white matter (WM) volumetric
      features and their impact on cognitive symptoms in PD. Therefore, the present
      study aims to examine both GM and WM volumes of cognitively asymptomatic PD
      patients with a longitudinal design. METHODS: A total of 42 cognitively
      asymptomatic patients with early stage PD were recruited and followed up for 1.5
      years. At follow-up, 12 patients progressed to mild cognitive impairment (MCI)
      and were classified as "converters" while the remaining 30 patients remained
      cognitively asymptomatic and were classified as "non-converters". All patients
      underwent clinical and neuropsychological assessments as well as MRI scans at
      baseline and at follow-up. RESULTS: At baseline, non-converters and converters
      had comparable cognitive scores. At follow-up, converters showed more deficits in
      frontal-related cognitive function than non-converters. Volumetric analyses
      revealed that converters had more longitudinal reduction in WM, but not GM,
      volume compared to non-converters. The decreased volumes among converters were
      mainly localized in the frontal areas. Moreover, baseline global WM volume
      significantly predicted conversion to PD-MCI, while baseline GM and WM volumes of
      the frontal and parietal regions were associated with frontal cognitive changes
      across time. CONCLUSION: PD patients who develop MCI demonstrate longitudinal
      reduction in WM volume, especially in the frontal areas. While both regional GM
      and WM volumes associate with frontal cognitive decline, baseline global WM
      volume may be a neuroimaging marker of conversion to PD-MCI.

PMID- 25753848
TI  - DEGRO guidelines for the radiotherapy of non-malignant disorders : part III:
      hyperproliferative disorders.
AB  - BACKGROUND AND PURPOSE: Radiation therapy (RT) is an established and effective
      treatment modality in the management of a large variety of hyperproliferative
      disorders and benign neoplasms. Objective of this article is to summarize the
      updated DEGRO consensus S2e guideline recommendations. MATERIALS AND METHODS:
      This report comprises an overview of the relevant aspects of the updated
      guidelines with regard to treatment decision, dose prescription, and RT technique
      for a selected group of disorders including Morbus Dupuytren (MD)/Morbus
      Ledderhose (ML), keloids, Peyronie's disease (induratio penis plastica, IPP),
      desmoid tumors, pigmented villonodular synovitis (PVNS), symptomatic vertebral
      hemangiomas (sVH), and Gorham-Stout syndrome (GSS). On the basis of results in
      the literature, we attempted to classify the level of evidence (LoE) and the
      grade of recommendation (GR) according to the Oxford criteria. RESULTS: There is
      comprehensive evidence in the literature that RT is a reasonable and effective
      treatment modality for the treatment of all the above-mentioned disorders. The
      LoE varies from 2c to 4, and GR varies from A to C. CONCLUSIONS: The use of RT
      can be recommended for the interdisciplinary management of most of the reported
      disorders. It can be used in the primary treatment approach and as an effective
      adjunct to other treatment modalities or in some indications as a valuable
      alternative treatment option. We hope that the updated DEGRO S2e consensus
      guideline recommendations are a helpful tool for radiation oncologists in the
      clinical decision-making process.

PMID- 25753849
TI  - Decomposition of drug mixture in Fenton and photo-Fenton processes: comparison to
      singly treatment, evolution of inorganic ions and toxicity assay.
AB  - The degradation of three pharmaceutical compounds i.e. chloramphenicol (CHPL),
      ciprofloxacin (CIP) and dipyrone (DIPY) singly and from equimolar (CCD) mixture
      has been investigated in Fenton and photo-Fenton processes. Drug mineralization
      was slightly less when present singly than their mixture. The degradation
      efficiency was likely hindered due to formation of common ions like Cl(-), F(-),
      NH4(+) and NO3(-). Addition of the same ions i.e. Cl(-) and F(-) in drug solution
      released upon cleavage of CHPL and CIP in CCD mixture suppressed the
      decomposition efficiency remarkably in both the oxidation processes. The major
      intermediates appeared in the mass spectra in combination of ion chromatograph
      were used to validate the routes of CCD decomposition and evolution inorganic
      ions. Furthermore, the bacterial toxicity assay was investigated using
      Escherichia coli (E. coli). The average reduction in cell death was about 38% in
      CCD system compared to 52%, 42% and 47% for CHPL, CIP and DIPY, respectively.

PMID- 25753850
TI  - Survey of perfluoroalkyl acids (PFAAs) and their precursors present in Japanese
      consumer products.
AB  - Perfluoroalkyl acids (PFAAs) and their precursors have been used in various
      consumer products. However, limited information regarding their occurrence and
      concentration levels in products is available. In this study, we investigated 18
      PFAAs and 14 PFAA precursors in various categories of consumer products purchased
      in Japan. Relatively high total concentrations of PFAAs and their precursors were
      found in sprays for fabrics and textiles (<limit of quantitation (LOQ)-30000 ng
      g(-1)) and car wash/coating products (<LOQ-7500 ng g(-1)) compared to other
      categories, and the similar observation was found in previous studies in Norway
      and Germany. A precursor of perfluorooctane sulfonic acid (PFOS), N-methyl
      perfluorooctane sulfonamidoethanol (MeFOSE) was detected in a higher frequency
      (8%) and in greater concentrations (<LOQ-3600+/-1800 ng g(-1)) than PFOS
      (frequency 4%; concentrations<LOQ-59+/-10 ng g(-1)). These results indicate that
      careful control of PFOS precursors in consumer products is required. Furthermore,
      the amount of PFAAs emitted from consumer products may be underestimated if the
      occurrence of PFAA precursors is not considered. In addition to PFAA precursors,
      long chain perfluoroalkyl carboxylic acids (PFCAs) (carbon chain length?7) were
      also detected in greater concentrations than short chain PFCAs (?6). This result
      suggests that consumer products are one of the important sources of long-chain
      PFCAs in the environment.

PMID- 25753851
TI  - Investigating landfill leachate as a source of trace organic pollutants.
AB  - Landfill leachate samples (n=11) were collected from five USA municipal solid
      waste (MSW) landfills and analyzed for ten trace organic pollutants that are
      commonly detected in surface and municipal wastewater effluents (viz.,
      carbamazepine, DEET, fluoxetine, gemfibrozil, PFOA, PFOS, primidone, sucralose,
      sulfamethoxazole and trimethoprim). Carbamazepine, DEET, PFOA and primidone were
      detected in all leachate samples analyzed and gemfibrozil was detected in samples
      from four of the five-landfill sites. The contaminants found in the highest
      concentrations were DEET (6900-143000 ng L(-1)) and sucralose (<10-621000 ng L(
      1)). Several compounds were not detected (fluoxetine) or detected infrequently
      (sulfamethoxazole, trimethoprim and PFOS). Using the average mass of DEET in
      leachate amongst the five landfills and scaling the mass release from the five
      test landfills to the USA population of landfills, an order of magnitude estimate
      is that over 10000 kg DEET yr(-1) may be released in leachate. Some
      pharmaceuticals have similar annual mean discharges to one another, with the
      estimated annual discharge of carbamazepine, gemfibrozil, primidone equating to
      53, 151 and 128 kg year(-1). To the authors knowledge, this is the first time
      that primidone has been included in a landfill leachate study. While the
      estimates developed in this study are order of magnitude, the values do suggest
      the need for further research to better quantify the amount of chemicals sent to
      wastewater treatment facilities with landfill leachate, potential impacts on
      treatment processes and the significance of landfill leachate as a source of
      surface water contamination.

PMID- 25753852
TI  - Oil sands naphthenic acids: a review of properties, measurement, and treatment.
AB  - The Alberta oil sands contain one of the world's largest reserves of oil - over
      169 billion barrels of bitumen are economically recoverable with current
      extraction technologies. Surface mining and subsequent hot water extraction of
      bitumen from the ore generates about nine cubic meters of raw tailings per cubic
      meter of oil. Oil sands facilities are required to operate under a policy of zero
      water discharge, resulting in ponds containing more than one billion cubic meters
      of tailings, a mixture of sand, fines and process-affected water. Process
      affected water contains numerous organic compounds, including naphthenic acids
      (NAs), which have been identified as the primary source of acute toxicity of
      process-affected water. Developments in analytical techniques, aerobic
      biodegradability, and treatment via chemical oxidation (ozone) of NAs are
      reviewed. The field continues to be challenged by the lack of a cost-effective,
      accurate analytical technique for NAs or an understanding of all the organic
      constituents in process-affected water that may be contributing to observed
      toxicity and thus requiring treatment. 

PMID- 25753853
TI  - Treatment of complex periorbital venolymphatic malformation in a neonate with a
      combination therapy of sirolimus and prednisolone.
AB  - Venolymphatic malformations (VLMs) are vascular anomalies consisting of both
      veins and lymph vessels. A 2-week-old newborn presented with large VLMs on the
      left forehead, temple, preauricular area, and orbit. Patient was at imminent risk
      for permanent vision loss due to a localized mass effect. Surgical excision or
      debulking was contraindicated due to its complexity and proximity to the left
      eye, and the patient failed to respond to the sildenafil treatment and
      sclerotherapy. Patient was subsequently started on oral sirolimus 0.8 mg/m(2)
      twice daily in combination with prednisolone 2 mg/kg daily. The patient had an
      excellent therapeutic outcome for 7 months with complete preservation of vision
      before treatment was discontinued. However, 2 months after the medical treatments
      were discontinued, her VLM rebounded. She responded to the combination therapy
      again after a failed treatment with the mTOR inhibitor alone. This case
      demonstrates that the sirolimus and prednisolone combination therapy could be
      beneficial for treatment of complex VLM intractable to other treatments. 

PMID- 25753854
TI  - Does major noncardiac surgery accelerate the progression of aortic stenosis? -
      Role of inflammation.

PMID- 25753855
TI  - Lipid core abutting lumen - optical coherence tomography-verified thin-cap
      fibroatheroma surrogate.

PMID- 25753856
TI  - Timing of anticoagulation therapy in patients with acute cardioembolic stroke.

PMID- 25753857
TI  - Inoculation of tannin-degrading bacteria into novel hosts increases performance
      on tannin-rich diets.
AB  - It has been hypothesized that herbivores host tannin-degrading bacteria (TDB) to
      overcome the toxic challenges posed by plant tannins. While TDB have been
      isolated from the guts of numerous mammals, their functional significance to
      their hosts has never been explicitly tested. We introduced TDB into lab rats,
      which do not host TDB, and measured host performance on tannin-rich diets. We
      first isolated three species of TDB, Escherichia coli, Bacillus subtilis and
      Enterococcus faecalis, from the guts of the desert woodrat (Neotoma lepida),
      which regularly feeds on tannin-rich plants. Then, we inoculated isolated TDB, as
      well as full woodrat microbial communities into laboratory rats. A control group
      was inoculated with sterilized woodrat faeces. Recipient lab rats were fed
      increasing concentrations of tannic acid, and we monitored tannic acid intake,
      body mass and liver damage as measured by serum alanine aminotransferase
      activity. Lab rats given TDB as isolates or full communities exhibited increased
      tannic acid intake, higher maintenance of body mass and lower indicators of liver
      damage compared with control animals. These differences were maintained when the
      trial was repeated after 6 weeks of feeding on tannin-free diets. Our results are
      the first to demonstrate that TDB significantly increase host performance on
      tannin-rich diets.

PMID- 25753858
TI  - Assessment of the Internal Fit of Lithium Disilicate Crowns Using Micro-CT.
AB  - PURPOSE: The aim of this study was to compare the internal fit of lithium
      disilicate crowns fabricated using digital technology with those fabricated by
      conventional means. MATERIALS AND METHODS: Forty-five lithium disilicate crowns
      were fabricated: 15 using digital impression and computer-aided design/computer
      aided machining technique (group 1), 15 from the same digital impressions, but
      using a conventional die and laboratory fabrication process (group 2), and 15
      using a conventional poly (vinyl siloxane) (PVS) impression and laboratory
      fabrication process (group 3). Tooth #15 was prepared for all-ceramic restoration
      on an ivorine typodont, which was digitized and a replica milled in zirconia to
      serve as master model. The master zirconia model was used for the impression
      procedures. Duplicate dies of the master zirconia die were made in polyurethane,
      enabling the internal fit of each crown to be evaluated using X-ray microcomputed
      tomography. The total volume of the internal space between the crown and die, the
      mean and maximum thickness of this space, and the percentage of the space that
      was at or below 120 MUm thickness was calculated for each group and statistically
      tested for significant difference using one-way ANOVA, with post hoc Scheffe
      analysis. RESULTS: Group 1 crowns resulted in a smaller volume of internal space
      (12.49 +/- 1.50 mm(3)) compared to group 2 (15.40 +/- 2.59 mm(3) ) and to those
      of group 3 (18.01 +/- 2.44 mm(3)). The mean thickness of the internal space for
      group 1 (0.16 +/- 0.01 mm) and for group 2 (0.17 +/- 0.03 mm) was significantly
      lower than that of group 3 (0.21 +/- 0.03 mm). The average percentage of the
      internal space of a thickness of 120 MUm and below was different between the
      three groups: 46.73 +/- 5.66% for group 1, 37.08 +/- 17.69% for group 2, and
      22.89 +/- 9.72% for group 3. Three-dimensional renderings of the internal space
      were also created. CONCLUSIONS: The results of this study suggested that pressed
      and milled IPS e. max crowns from LAVA COS digital impressions had a better
      internal fit to the prepared tooth than pressed IPS e.max crowns from PVS
      impressions in terms of total volume of internal space, average thickness of
      internal space, and percentage of internal space at or below 120 MUm.

PMID- 25753859
TI  - Beneficial effects of intramyocardial mesenchymal stem cells and VEGF165 plasmid
      injection in rats with furazolidone induced dilated cardiomyopathy.
AB  - To explore the impact of myocardial injection of mesenchymal stem cells (MSCs)
      and specific recombinant human VEGF165 (hVEGF165 ) plasmid on collagen
      remodelling in rats with furazolidone induced dilated cardiomyopathy (DCM). DCM
      was induced by furazolidone (0.3 mg/bodyweight (g)/day per gavage for 8 weeks).
      Rats were then divided into four groups: (i) PBS group (n = 18): rats received
      equal volume myocardial PBS injection; (ii) MSCs group (n = 17): 100 MUl culture
      medium containing 10(5) MSCs were injected into four sites of left ventricular
      free wall (25 MUl per site); (iii) GENE group (n = 18): pCMVen-MLC2v-EGFP-VEGF165
      plasmid [5 * 10(9) pfu (0.2 ml)] were injected into four sites of left
      ventricular free wall (0.05 ml per site)] and (iv) MSCs+GENE group (n = 17): rats
      received both myocardial MSCs and pCMVen-MLC2v-EGFP-VEGF165 plasmid injections.
      After 4 weeks, cardiac function was evaluated by echocardiography. Myocardial
      mRNA expressions of type I, type III collagen and transforming growth factor
      (TGF)-beta1 were detected by RT-PCR. The protein expression of hVEGF165 was
      determined by Western blot. Myocardial protein expression of hVEGF165 was
      demonstrated in GENE and MSCs+GENE groups. Cardiac function was improved in MSCs,
      GENE and MSCs+GENE groups. Collagen volume fraction was significantly reduced and
      myocardial TGF-beta1 mRNA expression significantly down-regulated in both GENE
      and MSCs+GENE groups, collagen type I/III ratio reduction was more significant in
      MSCs+GENE group than in MSCs or GENE group. Myocardial MSCs and hVEGF165 plasmid
      injection improves cardiac function possibly through down-regulating myocardial
      TGF-beta1 expression and reducing the type I/III collagen ratio in this DCM rat
      model.

PMID- 25753860
TI  - Association of the dispersion in red blood cell volume with mortality.
AB  - BACKGROUND: The red cell distribution width (RDW) predicts mortality among many
      populations. RDW is calculated as the standard deviation (SD) of the red blood
      cell (RBC) volume divided by mean corpuscular volume (MCV). Because higher MCV
      also predicts mortality, we hypothesized that the RDW numerator (one SD of RBC
      volume or 1SD-RDW) predicts mortality more strongly than the RDW. MATERIAL AND
      METHODS: Adult subjects hospitalized during a contemporary clinical era (10/2005
      1/2014, N = 135,963) and a historical era (1/1999-9/2005, N = 119,530) were
      studied. The RDW was obtained from the complete blood count (CBC), while 1SD-RDW
      was calculated (RDW multiplied by MCV and divided by 100). RESULTS: In
      univariable Cox regression (2005-2014 cohort), 1SD-RDW (quintile 5 vs. 1: hazard
      ratio [HR] = 8.38, 95% confidence interval [CI] = 7.94, 8.85; P < 0.001) was a
      superior predictor of mortality compared to RDW (quintile 5 vs. 1: HR = 4.78, CI
      = 4.57, 5.00; P < 0.001). This superiority remained after adjustment for age,
      sex, basic metabolic profile components and other CBC factors excluding MCV (1SD
      RDW: HR = 2.41, CI = 2.28, 2.55; RDW: HR = 2.01, CI = 1.92, 2.11). Further
      adjustment for MCV strengthened the RDW association (HR = 2.14, CI = 2.04, 2.24;
      P < 0.001), becoming indistinct from 1SD-RDW (HR = 2.20, CI = 2.08, 2.33; P <
      0.001). Findings were similar for the 1999-2005 cohort. CONCLUSIONS: The 1SD-RDW
      predicted mortality more strongly than RDW, suggesting that 1SD-RDW is superior
      to RDW as an individual risk predictor. Further, these results indicate that the
      dispersion of RBC volume and its mean are independent risk markers. Further
      research is required to understand the clinical value and mechanistic basis of
      these associations.

PMID- 25753861
TI  - Asthma diagnosis: addressing the challenges.

PMID- 25753862
TI  - Mean platelet volume in retinal vein occlusion.

PMID- 25753863
TI  - Letter to the editor, in response to the letter entitled: is obesity influence
      serum brain-derived.

PMID- 25753864
TI  - Is obesity influence serum brain-derived neurotrophic factor level in adults?

PMID- 25753865
TI  - Open, laparoscopic and robot-assisted laparoscopic radical prostatectomy:
      comparative analysis of operative and pathologic outcomes for three techniques
      with a single surgeon's experience.
AB  - OBJECTIVE: To compare outcomes of open (O-), laparoscopic (L-) and robot-assisted
      laparoscopic (RAL-) radical prostatectomy (RP) performed by the same surgeon.
      PATIENTS AND METHODS: From May 1999 to April 2012, 484 RPs were performed by a
      single surgeon. Patients' data including age, body-mass index, serum prostate
      specific antigen (PSA) level, Gleason score of prostate biopsy and prostatectomy
      specimen, preoperative prostate and specimen volumes, clinical and pathologic
      stages, operation time, estimated blood loss (EBL), catheterization time, blood
      transfusion rate were recorded. Prospectively collected data was evaluated
      retrospectively by statistical analyses. RESULTS: Of 484 radical prostatectomies,
      ORP (50), LRP (308) and RALRP (79) done by the same surgeon were included into
      study. Mean ages were 63.8, 62.7 and 60.3 years for ORP, LRP and RALRP
      respectively. Operation times for ORP, LRP and RALRP were 255, 208 and 242
      minutes. EBL and hospitalization time were 602, 526, 234 mL, and 9.1, 3.2, 3.2
      days for ORP, LRP and RALRP, respectively. While a significant advantage was
      found for EBL and complication rates in RALRP and for operation time in LRP,
      significant disadvantages were found in terms of catheterization time,
      hospitalization time, decrease in hemoglobin and blood transfusion in ORP.
      However, preoperative prostate volume and serum PSA level, oncologic outcomes and
      positive surgical margins were nearly similar in all operative techniques.
      CONCLUSIONS: Minimally invasive techniques such as LRP and RALRP are promising
      techniques with comparable outcomes with ORP. Shorter catheterization time, less
      blood loss and fewer complication rates can be provided by RALRP.

PMID- 25753866
TI  - Advantages of microsurgical varicocelectomy over conventional techniques.
AB  - OBJECTIVE: Varicocelectomy is the only effective method of treating varicocele.
      Nowdays, many techniques for varicocelectomy include retroperitoneal, inguinal,
      and subinguinal varicocele repairs with or without magnification and laparoscopic
      repair. The advantages of the microsurgical approach to varicocele repairs are
      reliable identification and preservation of the vascular structures. Thus, our
      aim is to compare the efficiency of microsurgery over conventional techniques of
      varicocele repairs. PATIENTS AND METHODS: We have evaluated 105 man divided into
      three groups of 35 patients surgically treated with open varicocelectomy in the
      first group, microsurgical varicocelectomy in the second, and laparoscopic
      varicocelectomy in the third group. Sperm test improvement and complications were
      then compared. RESULTS: The testicular volume shows a significant increase after
      all three types of surgery, the highest one being after the laparascopic
      varicocelectomy (14.47 +/- 6.76 vs. 21.8 +/- 7.52), whereas the lowest increase
      was recorded in open varicocelectomy (14.90 +/- 6.26 vs. 17.46 +/- 5.89).
      Regarding motility of spermatozoids, the highest postoperative increase of values
      is after microsurgical varicocelectomy (4.30 +/- 2.19 vs. 15.88 +/- 3.13).
      CONCLUSIONS: Our study shows the lowest degree of postoperative complications
      among patients treated with microsurgical varicocelectomy, and the most frequent
      complications in those treated by open varicocelectomy. Sperm test outcomes after
      microsurgical varicocelectomy was better than those after other conventional
      techniques: significantly higher improvement of sperm quality, shoter
      postsurgical clinical treatment, and the lowest rate of postsurgical
      complications.

PMID- 25753867
TI  - The comparison of microdose flare-up and multiple dose antagonist protocols based
      on hCG day estradiol (E2), progesterone (P) and P/E2 ratio among poor responder
      patients in ICSI-ET cycles.
AB  - OBJECTIVE: Elevated progesterone levels surpassing exact treshold values impede
      endometrial receptivity and decrease clinical pregnancy rates in different
      responder patients during assisted reproductive techniques. A progesterone (P):
      estradiol (E2) ratio of > 1 on the day of hCG administration has also been
      suggested to be a manifestation of low ovarian reserve. The clinical significance
      of P/E2 ratio on the day of hCG administration was investigated among poor
      responder patients. PATIENTS AND METHODS: Based on the ESHRE Bologna consensus
      criteria related to poor ovarian response diagnosis, 48 poor responder patients
      were treated with the microdose flare-up regimen and 34 patients were treated
      with the multiple-dose GnRH antagonist protocol. All patients were destined to
      perform a ICSI-ET procedure at the end of the stimulation protocols. Progesterone
      levels and P/E2 ratios have been detected during controlled ovarian
      hyperstimulation. RESULTS: In the microdose flare-up group; the duration of
      stimulation, total gonadotropin dose used and hCG day E2 levels were
      significantly higher than the multiple dose antagonist group. However, the mean
      hCG day P/E2 rate in the microdose flare-up group was less than that in the
      multiple-dose antagonist group. The clinical pregnancy rates were non
      significantly higher in the multiple dose antagonist protocol group than in
      microdose flare-up group. CONCLUSIONS: Impaired endometrial receptivity caused by
      elevated P levels results with lower pregnancy rates. Regardless of the selected
      stimulation protocol, poor responder patients are not prone to exhibit high P and
      E2 secretion. Increased P/E2 ratio of > 1 on hCG day has limited value to predict
      cycle outcomes in poor responder patients because of ovarian follicle depletion.

PMID- 25753868
TI  - MicroRNA-195 induced apoptosis in hypoxic chondrocytes by targeting hypoxia
      inducible factor 1 alpha.
AB  - OBJECTIVE: The chondrocytes, the resident cells of cartilage, are maintained and
      take effects in the whole life upon chronic hypoxic exposure, which hypoxia
      inducible factor 1 alpha (HIF-1alpha) play pivotal roles in response to.
      Dysregulation of some microRNA (miRNAs) have also been identified to be involved
      in hypoxia-related physiologic and pathophysiologic responses in some tissues or
      cell lines. However, the mechanism of miRNAs reponse to hypoxia remain largely
      unknown in chondrocytes, including the microRNA-195 (miR-195). AIM To investigate
      the effects of microRNAs (miRNAs) and hypoxia-inducible factor 1 alpha (HIF
      1alpha) on chondrocytes in physiologic environment. MATERIALS AND METHODS: We
      compared the expression of miR-195 and HIF-1alpha mRNA on hypoxia with that on
      normoxia in ATDC 5 cells by qRT-PCR. Further experiments was performed to
      confirmed the relationships of miR-195 and HIF-1alpha by bioinformatics analysis
      and dual reporter gene assay. we also assessed the effect of miR-195 on apoptosis
      in hypoxic ATDC 5 cells by transfect with miR-195 mimics. RESULTS: It was found
      the downregulated miR-195 and upregulated HIF-1alpha were present in hypoxic ATDC
      5 cells. miR-195 negatively regulated HIF-1alpha by targeting its 3'-untranslated
      region. Moreover, the founding indicated miR-195 greatly increased apoptosis and
      downregulated HIF-1alpha mRNA occurred simultaneously in hypoxic chondrocytes.
      CONCLUSIONS: We concluded that miR-195 induced apoptosis in hypoxic chondrocytes
      by directly targeting HIF-1alpha.

PMID- 25753869
TI  - Comparative evaluation of 2.0 mm locking plate system vs 2.0 mm non-locking plate
      system for mandibular angle fracture fixation: a prospective randomized study.
AB  - OBJECTIVE: This prospective randomized study evaluated the efficacy of a 2.0 mm
      locking plate/screw system compared with a 2.0-mm nonlocking plate/screw system
      in fixation of 60 isolated non-comminuted mandibular angle fractures. PATIENTS
      AND METHODS: Sixty patients were randomly assigned to receive a 2.0 mm locking
      plate (group A, n = 30) or 2.0 mm non-locking plate (group B, n = 30). All
      patients were followed up to 6 months postoperatively and evaluated for
      complications, occlusal stability and overall results of fixation. RESULTS: Five
      complications occurred in the locking group and fourteen in the non-locking group
      with complication rates equalling 17% and 47% respectively. When comparing the
      overall results according to plates used, the chi2 test showed a statistically
      significant difference between the locking and non-locking plates (p < 0.01).
      Fewer patients required IMF in group A. CONCLUSIONS: Mandibular angle fractures
      treated with 2.0 mm locking plates show greater stability and were associated
      with fewer complications than with 2.0 mm non-locking plates.

PMID- 25753870
TI  - Biomarkers of low-grade inflammation in primary varicose veins of the lower
      limbs.
AB  - OBJECTIVE: To analyze serum biomarkers of CVD in selected patients with primary
      axial reflux of great saphenous vein in one or both lower limbs. PATIENTS AND
      METHODS: Ninety-six patients affected by uncomplicated varicose veins, were
      enrolled in the study. A unilateral, primary axial reflux in great saphenous
      veins was detected in 54 patients (U-CVD group) and a bilateral one in 42 (B-CVD
      group). Sixty-five age and sex-matched subjects without venous reflux were
      enrolled as controls. Mean venous pressure of both lower limbs at the distal
      great saphenous vein (mGSVP) and venous reflux were measured by continuous-wave
      Doppler ultrasound and echoduplex scanning, respectively. Reactive Oxygen Species
      (ROS), tissue Plasminogen Activator (t-PA) and its Inhibitor 1 (PAI-1)
      activities, Hematocrit (HTC), White Blood Cells (WBC), Neutrophyls (NEU),
      Platelets (PLT), Fibrinogen (FIB) and Blood Viscosity (BV) were assessed in blood
      samples drawn from the antecubital vein. RESULTS: B-CVD group showed higher
      fibrinogen values (p < 0.005) and higher mean venous pressure (0 < 0.0001) in
      comparison to controls, while U-CVD did not. No difference was found between both
      groups and controls for all the other parameters. CONCLUSIONS: Increased
      fibrinogen levels in patients with bilateral varicose veins may represent an
      early warning signal, as it could be associated to the long-term progression of
      chronic venous disease.

PMID- 25753871
TI  - The association between the -2518A/G polymorphism in the MCP-1 gene and the risk
      of pulmonary tuberculosis in Sichuan Chinese population.
AB  - OBJECTIVE: The -2518A/G polymorphism in the Monocyte chemotactic protein-1 (MCP
      1) gene may play an important role in regulating immunological reactions and may
      be associated with pulmonary tuberculosis (PTB). However, the relationship for
      the populations in Sichuan province of China remains unknown. The objective of
      the current study was to analysis that association. PATIENTS AND METHODS: A total
      of 386 PTB patients and 398 controls were recruited. The genotypes were
      identified using PCR-RFLP and sequencing method. Data was analyzed using SPSS
      11.0 software. RESULTS: Significant association was found between the
      polymorphism and the risk of PTB: AG vs. AA: OR = 1.37, 95% CI = 0.98-1.92 and p
      = 0.06; GG vs. AA: OR = 1.69, 95% CI = 1.14-2.50 and p = 0.009; AG+GG vs. AA: OR
      = 1.47, 95% CI = 1.07-2.01 and p = 0.02; G vs. A: OR = 1.31, 95% CI = 1.08-1.60
      and p = 0.007. CONCLUSIONS: The current study suggested that the 2518A/G
      polymorphism in the MCP-1 gene was associated with risk of PTB in population of
      Sichuan province in China.

PMID- 25753872
TI  - In-hospital mortality due to infectious disease in an Internal Medicine
      Department. Epidemiology and risk factors.
AB  - OBJECTIVE: Hospital mortality is a leading indicator of quality of healthcare and
      a valuable tool for planning and management. Infectious diseases represent a
      substantial part of the activity of internal medicine.Our aim was to describe the
      characteristics of in-hospital mortality due to infectious diseases and
      associated risk factors in our environment. MATERIALS AND METHODS: A
      retrospective case-control study was designed. We reviewed deaths during 2012
      from an Internal Medicine Department. 187 cases (infectious disease related
      mortality) and 224 controls were found. Clinical and demographic information was
      obtained from medical records. Comorbidity was evaluated with Charlson index
      (CI). Data were analyzed using SPSS 15.0 (p-value < 0.05). RESULTS: During 2012,
      of the 3193 discharge, 187 were exitus due to infectious disease (5.8%). Mean age
      was 85.7 +/- 7.6, higher in women (88 +/- 7 vs 83 +/- 7.4, p < 0.001), and 55%
      were aged over 85 years. The CI mean was 4.2 +/- 3, higher in younger than 85
      years (5.3 +/- 3.4 vs 3.6 +/- 2.6, p < 0.001). Most frequent causes of death were
      respiratory sepsis (29%), severe pneumonia (23.5%) and urinary sepsis (16.6%) and
      risk factors were living in Nursing Home (55.6% vs 34%, p < 0.001), being
      dependent (73.8% vs. 44.6%, p < 0.001), dementia (59.4% vs 27.2%, p < 0.001) and
      cerebrovascular disease (25.7% vs 17.4%, p = 0.041). CONCLUSIONS: Dementia,
      cerebrovascular disease, living in Nursing Home and being dependent were risk
      factors for infectious disease in-hospital mortality in our study, but not
      comorbidity, age or length of stay. Our series, although limited by retrospective
      design, is the first qualitative study of in-hospital mortality due to infectious
      disease in an Internal Medicine Service in our environment. Most frequent cause
      of death in our setting was respiratory etiology.

PMID- 25753873
TI  - Usefulness of DuoPAP in the treatment of very low birth weight preterm infants
      with neonatal respiratory distress syndrome.
AB  - OBJECTIVE: This study examined the usefulness of nasal Duo positive airway
      pressure (DuoPAP) in the treatment of very low birth weight preterm infants with
      neonatal respiratory distress syndrome (NRDS). PATIENTS AND METHODS: Eighty-five
      very low birth weight preterm infants with NRDS were randomly divided into two
      groups. Forty-five infants were treated with DuoPAP, while 40 infants were
      treated using nasal continuous positive airway pressure (nCPAP). The study
      outcomes were pH, PaCO, PaO2, oxygenation index (PaO2/FiO2), and the number of
      failure cases at 1, 12, and 24 hours after non-invasive respiratory support.
      RESULTS: At all studied time points, after non-invasive respiratory support,
      PaCO2, PaO2 and oxygenation index were significantly (p < 0.05) better in the
      nasal DuoPAP group compared with nasal CPAP group. In addition, rates of failure
      of assisted ventilation (respectively, 4.44% vs. 22.50%) and the occurrence of
      apnea (13.33% vs. 32.50%) were significantly (p < 0.05) better in the nasal
      DuoPAP group. Other parameters (such as duration of noninvasive ventilation,
      number of retinopathies of premature children, intraventricular hemorrhages, or
      periventricular leukomalacias) were comparable between both non-invasive regimen.
      CONCLUSIONS: Nasal DuoPAP better improves oxygenation, reduces CO2 retention, and
      diminishes the need for invasive mechanical ventilation and complications in the
      treatment of NRDS.

PMID- 25753874
TI  - Effect evaluation of cisplatin-gemcitabine combination chemotherapy for advanced
      non-small cell lung cancer patients using microarray data.
AB  - OBJECTIVE: This study was performed to evaluate the therapeutic effect of
      cisplatin-gemcitabine combination chemotherapy for advanced non-small cell lung
      cancer (NSCLC). MATERIALS AND METHODS: Dataset GSE39345 from patients who
      underwent cisplatin-gemcitabine combination chemotherapy and normal controls was
      downloaded from Gene Expression Omnibus. Differentially expressed genes (DEGs)
      were identified using Limma package and divided into 3 datasets: unique DEGs in
      NSCLC before chemotherapy vs. control samples (dataset A), common DEGs (dataset
      B), unique DEGs in NSCLC after chemotherapy vs. control samples (dataset C).
      Enrichment analysis was to identify functions or pathways of DEGs. Protein
      protein interaction (PPI) analysis was to identify hub nodes and interacting
      pairs in dataset C and constructed into PPI network using Cytoscape software,
      followed by screening of small molecules using Connectivity Map. RESULTS: Herein,
      230 unique DEGs in dataset A, 584 common DEGs in dataset B and 1562 unique DEGs
      in dataset C were obtained. The 230 DEGs were significantly enriched in
      methylation and positive regulation of cell differentiation; the 584 DEGs were
      significantly enriched in positive regulation of cell differentiation and
      cytokine-cytokine receptor interaction pathway; the 1562 DEGs were enriched in
      functions associated with defense response. RELA and PLCB3 correlated with PLCE1
      and INADL were hub nodes in the PPI network. Cefoperazone was the small molecule
      negatively correlated with DEGs. CONCLUSIONS: Chemotherapy could prevent genes
      from aberrant methylation, partially restore cell differentiation process, fail
      to regulate cytokine-cytokine receptor interaction and induce weakened defense
      response. Cefoperazone could be used as a supplementary drug.

PMID- 25753875
TI  - Nimotuzumab with cisplatin or fluorouracil on human esophageal squamous cell
      carcinoma EC1 cells.
AB  - OBJECTIVE: To investigate the effects of nimotuzumab (h-R3) with cisplatin (DDP)
      or fluorouracil (5-FU) on human esophageal squamous cell carcinoma (ESCC) EC1
      cells. MATERIALS AND METHODS: The assignment included blank control, h-R3 alone,
      DDP alone, 5-FU alone, h-R3 combined with DDP, and h-R3 combined with 5-FU. The
      cell proliferation in each group was measured by MMT method 48 h post dose. The
      effect on the cell cycle was determined by flow cytometry, and the effect on cell
      apoptosis was determined by flow cytometry and TUNEL test 48 h post dose.
      RESULTS: The inhibitory effect of h-R3 on the proliferation of EC1 cells was
      weak. The maximum inhibition rate was 10.10 +/- 0.58% 48 h post dose, and the
      difference in the inhibition rate between the h-R3 with chemotherapeutic agents
      and the chemotherapeutic agent alone was not statistically significant (p >
      0.05). Flow cytometry demonstrated no obvious change in the EC1 cells after h-R3
      treatment (p > 0.05). Flow cytometry and TUNEL test demonstrated that the
      difference in the apoptosis rate between h-R3 combined with chemotherapeutic
      agents and blank control was not statistically significant (p > 0.05).
      CONCLUSIONS: h-R3 had no significant effect on human ESCC EC1 cells in vitro,
      with or without the combination of chemotherapeutic agents.

PMID- 25753876
TI  - Identifying hub genes and dysregulated pathways in hepatocellular carcinoma.
AB  - OBJECTIVE: The aim of this study was to identify the hub genes and dysregulated
      pathways of hepatocellular carcinoma (HCC) and explore the molecular mechanism of
      the biological process associated with HCC. MATERIALS AND METHODS: Microarray
      data were got from NCBI Gene Expression Omnibus (GEO) database. The most
      significant top 100 up-regulated gene signatures and top 100 down-regulated gene
      signatures were identified by integrated analysis of the multiple microarray
      datasets using a novel model genome-wide relative significance (GWRS) and genome
      wide global significance (GWGS). Gene Ontology (GO) enrichment analysis and
      pathway analysis of those genes were performed based on Gene Ontology website and
      Kyoto Encyclopedia of Genes and Genomes (KEGG). Protein-protein interaction (PPI)
      network was constructed using Cytoscape 2.1. In addition, we analysed the
      significantly dysregulated signaling pathways across the PPI network and KEGG
      pathway analysis. RESULTS: We screened 2920 up-regulated and 2231 down-regulated
      gene signatures across multiple studies by GWRS and GWGS. The top 100 up
      regulated and top 100 down-regulated gene signatures were selected for further
      research. GO enrichment analysis showed that these genes significantly enriched
      in terms of mitosis (p = 5.83*10-20), nuclear division (p = 5.83*10-20) and M
      phase of mitotic cell cycle (p = 9.39*10-20). The most significant terms of KEGG
      pathway included cell cycle (p = 1.33*10-8), oocyte meiosis (p = 1.41*10-4), drug
      metabolism (p = 2.15*10-4) and p53 signaling pathway (p = 3.57*10-4). PPI network
      suggested that BIRC5, CDC20, CCNB1, BUB1B, MAD2L1 and CDK1 were important
      significant genes which were considered as hub genes. Across the PPI and pathway,
      cell cycle, oocyte meiosis and p53 signaling pathway were the significantly
      dysregulated pathways. CONCLUSIONS: Our study displayed robust gene signatures in
      HCC. It showed that the dysregulations of cell cycle, oocyte meiosis, p53
      signaling pathway and progesterone-mediated oocyte maturation pathway were
      closely associated to the development and progression of HCC. Besides, genes
      BIRC5, CDC20, CCNB1, BUB1B, MAD2L1 and CDK1 as the hub genes might play important
      roles for diagnosing and therapy of HCC.

PMID- 25753877
TI  - Application of ultrasound technology in the diagnosis and treatment of digestive
      tract diseases.
AB  - Ultrasound is commonly used in clinical examination which is economic, non
      invasive and convenient. Ultrasound can be used for the examination of solid
      organs and hollow organs. Due to the presence of air, routine ultrasound
      examination of the digestive tract is not very appropriate, Because of the
      development of endosonography and its related technology, diagnosis and treatment
      of gastrointestinal diseases have been improved which is valuable in clinic. This
      review focused on the application of ultrasound technology in the diagnosis and
      treatment of digestive tract diseases. 

PMID- 25753878
TI  - miR-155 and miR-146b negatively regulates IL6 in Helicobacter pylori (cagA+)
      infected gastroduodenal ulcer.
AB  - OBJECTIVE: Helicobacter pylori (H. pylori) infection is the main cause of
      gastroduodenal ulcer. The molecular mechanisms that underlying this progress are
      still not very clear. MicroRNAs (miRNAs) are small noncoding RNAs that function
      as negative regulator of numerous target genes at posttranscriptional level.
      miRNAs plays important roles in the development of many infection related
      diseases. The roles of miRNAs in the development of H. pylori-infected
      gastroduodenal ulcer haven't been well studied yet. MATERIALS AND METHODS: The
      miRNA and mRNA profiles in normal gastroduodenal biopsy, H. pylori-infected
      gastroduodenal biopsy and H. pylori-infected gastroduodenal ulcer biopsy samples
      were compared and analyzed to identify potential related miRNAs and their target
      genes. The differential expression of the identified miRNAs and their target gene
      were validated in an independent set of H. pylori positive gastroduodenal ulcer
      biopsy samples by immunohistochemistry staining and RT-PCR. Then microRNA mimics
      were transfected to gastric epithelial cells infected with H. pylori 26695
      (cagA+). RT-PCR and Western blotting were performed to confirm the target gene of
      the identified microRNAs. RESULTS: The integrative analysis and
      immunohistochemistry staining validation indicated that miR-155 and miR-146b, as
      well as their predicted target gene IL6, are up-regulated in H. pylori positive
      gastroduodenal ulcer. Further experiments in gastric epithelial cells revealed
      that H. pylori 26695 (cagA+) infection induces IL6 overexpression. But the
      overexpression of IL6 is weaken due to negative regulation by miR-155 and miR
      146b. CONCLUSIONS: This study indicated that the up-regulation of miR-155 and miR
      146b decreases H. pylori (cagA+)-introduced IL6 overexpression, which might
      weaken the cleanup of H. pylori (cagA+) and contributes to ulcer.

PMID- 25753879
TI  - Association of fat-mass and obesity-associated gene FTO rs9939609 polymorphism
      with the risk of obesity among children and adolescents: a meta-analysis.
AB  - OBJECTIVE: To elucidate the association of fat-mass and obesity-associated gene
      (FTO) rs9939609 polymorphism with obesity among children and adolescents.
      METHODS: A literature search was conducted in PubMed, MEDLINE, Springer, and
      Google scholar to identify eligible studies. The pooled odds ratios (ORs) with
      95% confidence intervals (CIs) were used for four models: co-dominant model (AA
      vs. TT, AT vs. TT), dominant model (AA + AT vs. TT), recessive model (AA vs. AT +
      TT), and allelic model (A vs. T). Subgroup analyses stratified by ethnicity
      (Caucasian, others) and participants (children, children and adolescents) were
      assessed under allelic model. The heterogeneity and publication bias were
      examined. RESULTS: This meta-analysis included 12 eligible studies consisting
      5,000 cases and 9,853 controls. The results revealed that FTO rs9939609
      polymorphism was significantly associated with the increased risk of obesity in
      co-dominant model (AA vs. TT: OR = 1.91, 95% CI: 1.47-2.48, p < 0.01; AT vs. TT:
      OR = 1.18, 95% CI: 1.02-1.38, p = 0.03), dominant model (AA + AT vs. TT: OR =
      1.47, 95% CI: 1.35-1.59, p < 0.01), recessive model (AA vs. AT + TT: OR = 1.79,
      95% CI: 1.47-2.17, p < 0.01), and allelic model (A vs. T: OR = 1.39, 95% CI: 1.22
      1.58, p < 0.01). Similar results were obtained for the subgroup analyses
      stratified by ethnicity and participants under allelic model. CONCLUSIONS: FTO
      rs9939609 polymorphism is associated with the increased risk of obesity among
      children and adolescents, especially the homozygous carriers.

PMID- 25753880
TI  - Glucose-induced microRNA-17 promotes pancreatic beta cell proliferation through
      down-regulation of Menin.
AB  - OBJECTIVE: Menin, encoded by the Men1 gene, is responsible for beta-cell tumor
      formation in patients with multiple endocrine neoplasia type 1. Recently, Menin
      has been proven to negatively regulate beta-cell proliferation in several mouse
      models, including hyperglycemia. However, it is unclear how glucose regulates
      Menin expression in beta-cells. MATERIALS AND METHODS: In the present study,
      quantitative real-time reverse transcriptase-polymerase chain reaction analysis
      was performed to detect the expression levels of MicroRNAs in Min-6 cells treated
      with high glucose, in which we found that miR-17 was significantly up-regulated.
      RESULTS: Further studies using bioinformatic prediction, luciferase and protein
      expression analysis suggested that miR-17 could inhibit protein levels of Menin
      through targeting its 3'-untranslated region. CONCLUSIONS: Our results indicate
      that miR-17 might serve as an important intracellular target of glucose to
      mediate the mitogenic effect that glucose exerts in pancreatic beta-cells.

PMID- 25753881
TI  - Characteristics and management of gout patients in Europe: data from a large
      cohort of patients.
AB  - OBJECTIVE: To increase the knowledge of epidemiology and treatment of gout in a
      'real-life' setting, we conducted a large observational analysis (CACTUS) in two
      European countries, namely France and Greece. PATIENTS AND METHODS: This was a
      multicenter, cross-sectional, observational analysis, conducted in France and
      Greece. The analysis was conducted in a field-practice scenario, with both
      general practitioners and rheumatologists recruiting patients for inclusion.
      Treatment methods and drug prescriptions were left to the sole initiative of the
      participating physicians. A number of epidemiological and clinical
      characteristics were recorded in a single inclusion visit. Compliance to
      maintenance treatment was also monitored after the inclusion visit by monthly
      interview. RESULTS: In total 3079 patients were included. Hypertension was the
      most common co-morbidity (68%), followed by hypercholesterolemia (59%) and
      obesity (48%). Mean serum Uric Acid (sUA) concentration was 8.7 mg/dl. Almost all
      patients received life-style or dietary recommendations. At inclusion, 81.5% of
      patients were on a urate-lowering treatment. Most of these patients had been
      treated with allopurinol; this treat-ment had been interrupted for lack of
      reduction of sUA levels below 6 mg/dl (47%), lack of symptom relief (34%) or poor
      compliance (23%). At the inclusion visit, 98% of the patients were prescribed an
      urate-lowering treatment: 87% received febuxostat and 12% allopurinol alone.
      Satisfactory or very satisfactory compliance to febuxostat was recorded in 92% of
      the patients, versus 82% in patients on allopurinol. CONCLUSIONS: CACTUS provides
      an overview of characteristics of gouty patients and gout management. Education
      of patients by healthcare providers seem to be a pre-requisite to optimize the
      management of gout, a condition which remains poorly man-aged.

PMID- 25753882
TI  - Uric acid: friend or foe? Uric acid and cognitive function "Gout kills more wise
      men than simple".
AB  - OBJECTIVE: The association between hyperuricemia and cardiovascular risk is
      widely known, and hyperuricemia is associated with many pathological conditions
      due to its effect on the endothelial function and metabolic homeostasis. The aim
      of this study was to verify whether the available literature may support the
      hypothesis that uric acid has a protective and stimulating effect on the cerebral
      cortex. MATERIALS AND METHODS: We reviewed the actual knowledge of the positive
      effects of uric acid in terms of antioxidant action, neuroprotection, cognitive
      function, and intellectual performance. CONCLUSIONS: Uric acid has a stimulating
      effect on the cerebral cortex, and this could have allowed humans, compared with
      other animals, to develop higher brain mass volume, better intellectual
      performances, and maybe evolutionary supremacy. On the other, a growing body of
      evidence is accumulating on the independent association between uric acid and
      cardiovascular risk. A careful interpretation of uric acid levels is appropriate
      and necessary in different kinds of patients, both at risk of cardiovascular or
      neurodegenerative diseases, due to its contrasting significance.

PMID- 25753883
TI  - The gender difference in effect of sevoflurane exposure on cognitive function and
      hippocampus neuronal apoptosis in rats.
AB  - OBJECTIVE: Anesthesia and surgery can induce postoperative cognitive dysfunction.
      Ser-133 phosphorylation sites of cAMP-response element binding protein (CREB) is
      a key gene that mediate a variety of downstream transcription initiation factors,
      regulate neuronal survival and promote the expression of a large number of genes.
      Thus, CREB may play a role in this impairment. We hypothesize that and
      sevoflurane-induced cognitive impairment possibly via inhibiting the expression
      of CREB downstream genes and proteins. MATERIALS AND METHODS: To test this
      hypothesis, adult Sprague-Dawley rats were subjected to sevoflurane exposure and
      were tested with a series of behavioral experiments (open field, passive
      avoidance test and Morris water maze test) at different time (1 d to 95 d).
      Besides, blood gas changes and expiratory sevoflurane concentrations were
      examined at 2 h; the levels of phosphorylated CREB 1, the protein Bcl-2, Caspase
      8 and Caspase-3 were assessed at 1 week and 3 months after anesthesia. We also
      conducted a comparison in sevoflurane-induced cognitive impairment between male
      and female rats. RESULTS AND CONCLUSIONS: Here, we found that sevoflurane
      anesthesia can impair short-term cognitive function, which may be via down
      regulating p-CREB1 and Bcl-2 expression and up-regulating Caspase-8 expression to
      reduce hippocampus neuronal apoptosis, and male rats suffered a more severe
      cognitive dysfunction than female rats. In addition, sevoflurane can produce a
      reversible long-term cognitive dysfunction in rats.

PMID- 25753884
TI  - Effects of sodium arsenite on the some laboratory signs and therapeutic role of
      thymoquinone in the rats.
AB  - OBJECTIVE: Serious health problems in humans are caused by arsenic (As) exposure,
      which is wide spread in the environment. Sodium arsenite (SAs), capable of
      inducing macromolecular damage is evaluated for its damaging effect in the blood
      vessels, liver and kidneys of Wistar rats. This study was undertaken to
      investigate the ameliorative effects of thymoquinone on SAs-induced oxidative and
      inflammatory damages in the serum of male Wistar rats. MATERIALS AND METHODS:
      Wistar Albino rats divided into three groups of nine rats each were administered
      to controls saline (10 mg/kg), SAs (10 mg/kg), and SAs plus thymoquinone (10
      mg/kg/day) for two weeks orally. Biochemical tests were analyzed by a
      otoanalyzer; nitric oxide levels specthrophometrically, and cytokines were
      measured by ELISA method in the rat serum samples. RESULTS: Inflammatory
      cytokines and some biochemical variables were found to be increased in the SAs
      group compared to control group. On the other hand, thymoquinone supressed these
      laboratory signs, which are thought to be the characteristic signs of SAs
      toxicity, most probably by its ameliorative effects including anti-inflammatory
      and antioxidant properties. CONCLUSIONS: From the results obtained, thymoquinone
      mitigates SAs-induced adverse effects in the serum of rats, which suggest that it
      may attenuate inflammation implicated in endotelial dysfunction.

PMID- 25753885
TI  - The effects of thiamine and thiamine pyrophosphate on alcohol-induced hepatic
      damage biomarkers in rats.
AB  - OBJECTIVE: This study examined the effects of thiamine and thiamine pyrophosphate
      on oxidative damage developing in association with hepatic injury caused by
      alcohol toxicity in rats and on hepatic injury markers. MATERIALS AND METHODS:
      Four groups of rats were used; control, a group receiving thiamine+ethanol, a
      group receiving thiamine pyrophosphate+ethanol and a healthy group. The
      experimental protocol was repeated over 30 days. Malondialdehyde, glutathione and
      DNA damage product levels in liver tissue were measured at the end of the study.
      Alanine amino transferase and aspartate amino transferase, markers of liver
      damage, levels were determined. The results were then compared among the groups.
      RESULTS: A statistically significant difference between antioxidant markers and
      markers of liver damage was determined between the group given thiamine
      pyrophosphate ethanol and the group given ethanol alone (p < 0.01) No
      statistically significant difference was observed between the group given
      thiamine and ethanol and the group given ethanol alone (p > 0.01). CONCLUSIONS:
      Our results suggest that thiamine pyrophosphate may have a protective effect
      against liver damage caused by alcohol toxicity.

PMID- 25753886
TI  - Amelioration of cardiotoxic impacts of diclofenac sodium by vitamin B complex.
AB  - OBJECTIVE: The safety of Non-steroidal anti-inflammatory drugs (NSAIDs) use in
      clinical practice has been questioned. Clinical studies indicate that these drugs
      cause adverse cardiovascular effects. The aim of this study was to investigate
      the protective role of vitamin B complex against the cardiotoxic potency of
      diclofenac sodium induced cardiac damage. MATERIALS AND METHODS: Diclofenac
      sodium was administered intraperitoneally to rats at either 1.5 mg or 3 mg/kg
      body weight for 14 consecutive days. Vitamin B complex (1.6 mg B1, 1.6 mg B6 and
      16.7 ug B12/kg body weight, i.p.) was co-administered daily for 3 weeks along
      with diclofenac administration to rats intoxicated by either of the two doses.
      RESULTS: The results revealed that co-administration of vitamin B complex with
      diclofenac to rats intoxicated by either of the two doses, markedly ameliorated
      increases in serum markers of cardiac damage, including, (AST), creatine kinase
      MB (CK-MB) as well as decreases in phosphoglucoisomerase (PGI) and lactate
      dehydrogenase (LDH) activities in cardiac tissue compared with intoxicated rats.
      The B complex also could markedly attenuate the decreases in cardiac antioxidant
      enzymes namely, glutathione reductase (GR), glucose-6-phosphate dehydrogenase (G
      6-PDH) and catalase (CAT) compared with diclofenac intoxicated rats. Beside, the
      vitamin B complex successfully modulated the increases in serum glucose, serum
      lipid profiles, triglycerides (TGs), total cholesterol (TCh) and low density
      lipoprotein (LDL-C) as well as the decrease in the high density lipoprotein (HDL
      C) in response to diclofenac toxicity. CONCLUSIONS: These results support the use
      of vitamin B complex along with diclofenac therapy as a protective agent against
      cardiac tissue damage induced by diclofenac toxicity.

PMID- 25753887
TI  - Effects of caffeic and chlorogenic acids on the rat skeletal system.
AB  - OBJECTIVE: Caffeic acid, predominantly as esters linked to quinic acid
      (chlorogenic acids), is a phenolic acid present at high levels in coffee. The aim
      of the study was to investigate effects of caffeic and chlorogenic acids on the
      skeletal system of female rats with normal estrogen levels and estrogen
      deficient. MATERIALS AND METHODS: Caffeic acid (5 and 50 mg/kg p.o. daily) and
      chlorogenic acid (100 mg/kg p.o. daily) were administered for 4 weeks to non
      ovariectomized and bilaterally ovariectomized mature Wistar rats, and their
      effects were compared with appropriate controls. Moreover, estradiol (0.2 mg/kg
      p.o. daily) was administered to ovariectomized rats. Bone turnover markers, mass,
      mineralization and mechanical properties were examined. RESULTS: Although caffeic
      acid at a low dose exerted some unfavorable effects on the skeletal system, at
      high doses, caffeic and chlorogenic acids slightly increased mineralization in
      the tibia and improved mechanical properties of the femoral diaphysis (compact
      bone). Unlike estradiol, they did not counteract the worsening of the tibial
      metaphysis bone strength (cancellous bone) and increases in osteocalcin
      concentration induced by estrogen deficiency. CONCLUSIONS: High doses of the
      phenolic acids slightly favorably affected the rat skeletal system independently
      of the estrogen status.

PMID- 25753888
TI  - The use of vancomycin with its therapeutic and adverse effects: a review.
AB  - OBJECTIVE: Vancomycin (VCM) is a tricyclic glycopeptide antibiotic produced by
      Streptococcus orientalis. Widely used in hospitals, it is indicated to fight
      severe infections caused by Gram-positive bacteria, especially with the advent of
      MRSA (methicillin-resistant Staphylococcus aureus), penicillin-resistant
      pneumococci among others. Furthermore, it is indicated for the treatment of
      patients allergic to penicillins and cephalosporins. Dose recommendations,
      dilution rates and types of infusion are controversial and also result in toxic
      effects. Aim of this paper was to perform a literature review showing the
      therapeutic and adverse effects of vancomycin. MATERIALS AND METHODS: This is a
      literature review of recent articles published on MEDLINE and SciELO databases in
      English, Portuguese and Spanish. RESULTS: The main adverse effects of vancomycin
      are: hypotension, phlebitis, nephrotoxicity, ototoxicity, hypersensitivity
      reactions, red man syndrome, neutropenia, chills, fever, interstitial nephritis.
      CONCLUSIONS: The use of vancomycin is still very common; however, inadequate
      doses and prolonged therapy pose a risk of increasing minimum inhibitory
      concentrations (MICs), resulting in subtherapeutic levels, treatment failures and
      toxicity. Therefore, further studies should be conducted to optimize the
      administration of vancomycin, monitoring treatments from the beginning in order
      to ensure a safe and effective use of the drug.

PMID- 25753889
TI  - A randomised controlled trial of a brief cognitive behavioural intervention for
      men who have hot flushes following prostate cancer treatment (MANCAN).
AB  - OBJECTIVE: Hot flushes and night sweats (HFNS) are experienced by up to 80% of
      prostate cancer patients undergoing androgen deprivation therapy (ADT). This
      study evaluates the effects of a guided self-help cognitive behavioural therapy
      (CBT) intervention on HFNS problem-rating (primary outcome), HFNS frequency, mood
      and health-related quality of life (secondary outcomes) in patients undergoing
      ADT. METHODS: Patients reporting treatment-induced HFNS were randomly assigned to
      CBT (n = 33) or treatment as usual (TAU) (n = 35), stratified for cancer type.
      The CBT intervention included a booklet, CD plus telephone contact during a 4
      week period. Validated self-report questionnaires were completed at baseline, 6
      weeks and 32 weeks after randomisation. The primary outcome was HFNS problem
      rating (perceived burden of HFNS) at 6 weeks after randomisation. Potential
      moderators and mediators were examined. Data analysis was conducted on a modified
      intention-to-treat basis. RESULTS: Compared with TAU, CBT significantly reduced
      HFNS problem rating (adjusted mean difference: -1.33, 95% CI -2.07 to -0.58; p =
      0.001) and HFNS frequency (-12.12, 95% CI -22.39 to -1.84; p = 0.02) at 6 weeks.
      Improvements were maintained at 32 weeks, but group differences did not reach
      significance. There were significant reductions in negative HFNS Beliefs and
      Behaviours following CBT, but not in mood or quality of life. CONCLUSIONS: Guided
      self-help CBT appears to be a safe and effective brief treatment for men who have
      problematic HFNS following prostate cancer treatments. Further research might
      test the efficacy of the intervention in a multicentre trial.

PMID- 25753890
TI  - Long-term follow-up is not indicated after routine interventional closure of
      persistent arterial ducts.
AB  - BACKGROUND: Little is known about the necessity for long-term follow-up after
      interventional closure of persistent arterial duct (PDA). Potential side effects
      and complications include residual shunts, haemolysis, device embolization, and
      obstruction to flow in the adjoining vessels. METHODS: Single centre
      retrospective study of paediatric patients undergoing interventional PDA
      occlusion. RESULTS: 315 patients who underwent interventional occlusion of a PDA
      between November 2002 and September 2013 were included. Of these, eight needed re
      intervention (three for device embolization, five for residual shunt). Seven had
      mild obstruction to flow in the adjoining vessels, but did not require any
      intervention. All sequelae were found latest at the first follow-up appointment
      after the procedure (usually within 3 months); whilst none developed during
      further follow-up. CONCLUSION: Complications of interventional closure of PDA
      were apparent immediately after the procedure or by three months of follow-up.
      Long-term follow-up is not indicated in cases when no complications are seen
      early after the procedure.

PMID- 25753891
TI  - Transient elastography spleen stiffness measurements in primary myelofibrosis
      patients: a pilot study in a single centre.

PMID- 25753892
TI  - A novel magnetic hydrogel with aligned magnetic colloidal assemblies showing
      controllable enhancement of magnetothermal effect in the presence of alternating
      magnetic field.
AB  - A novel magnetic hydrogel is formed via the field-directed assembly of magnetic
      nanomaterials during the gelation process. The novel magnetic hydrogel exhibits
      direction-dependent thermogenesis in an alternating magnetic field. The specific
      absorption rate value in the direction along the assemblies can be 2.1-fold as
      much as that in the direction normal to the assemblies while the heating rate is
      6-8-fold. Due to the anisotropic thermogenesis, the novel magnetic hydrogel also
      shows a direction-dependent release of drugs that has a 3.4-fold difference
      between the two directions. 

PMID- 25753893
TI  - Mir-23a induces telomere dysfunction and cellular senescence by inhibiting TRF2
      expression.
AB  - Telomeric repeat binding factor 2 (TRF2) is essential for telomere maintenance
      and has been implicated in DNA damage response and aging. Telomere dysfunction
      induced by TRF2 inhibition can accelerate cellular senescence in human
      fibroblasts. While previous work has demonstrated that a variety of factors can
      regulate TRF2 expression transcriptionally and post-translationally, whether
      microRNAs (miRNAs) also participate in post-transcriptionally modulating TRF2
      levels remains largely unknown. To better understand the regulatory pathways that
      control TRF2, we carried out a large-scale luciferase reporter screen using a
      miRNA expression library and identified four miRNAs that could target human TRF2
      and significantly reduce the level of endogenous TRF2 proteins. In particular,
      our data revealed that miR-23a could directly target the 3' untranslated region
      (3'UTR) of TRF2. Overexpression of miR-23a not only reduced telomere-bound TRF2
      and increased telomere dysfunction-induced foci (TIFs), but also accelerated
      senescence of human fibroblast cells, which could be rescued by ectopically
      expressed TRF2. Our findings demonstrate that TRF2 is a specific target of miR
      23a, and uncover a previously unknown role for miR-23a in telomere regulation and
      cellular senescence.

PMID- 25753894
TI  - The effects of depriving feed to facilitate transport and slaughter in sheep--a
      case study of cull ewes held off pasture for different periods.
AB  - AIM: To determine the ability of sheep to mobilise their body reserves after
      being deprived of feed prior to transport for slaughter. METHODS: A total of 240
      3- and 4-year-old cull ewes were held off pasture for 0, 9, 18 or 30 hours (n=60
      per group) then transported 1 hour by road, unloaded and washed, held in lairage
      for 3 hours then slaughtered. Blood samples were collected from a subsample of 60
      unfasted ewes 1 week earlier, and from all ewes at exsanguination to determine
      concentrations of serum metabolites indicative of adaptation to fasting. In
      addition, several attributes of carcass quality were measured. RESULTS: At
      slaughter, increased time off pasture prior to transport resulted in no change in
      glucose concentrations in serum (p=0.140). There were differences (p<0.001)
      between the group fasted for 30 compared with 0 hours in mean concentrations of
      free fatty acids (0.98 (SD 0.32) vs. 0.58 (SD 0.23) mmol/L), beta-hydroxybutyrate
      (0.69 (SD 0.17) vs. 0.42 (SD 0.11) mmol/L), triglycerides (0.29 (min 0.13, max
      0.83) vs. 0.22 (min 0.06, max 0.96) mmol/L) and urea (10.17 (SD 1.80) vs. 6.94
      (SD 2.03) mmol/L). Different periods of feed deprivation had no effect (p>0.05)
      on carcass weights (mean 22.7, min 13.2, max 32.9 kg) or dressing out percentages
      (mean 40.9, min 27, max 49%). Meat ultimate pH was unaffected (p>0.05) by the
      period of feed deprivation but meat became darker (p<0.05) and had reduced
      redness (p<0.001) with increasing time off feed. CONCLUSIONS: The results suggest
      that sheep in variable body condition adapted to the periods of feed deprivation
      by mobilising their energy reserves without any evidence of metabolic depletion
      (e.g. depleted blood glucose or high meat pH). However, being deprived of feed
      they probably experience a degree of hunger.

PMID- 25753895
TI  - Postprandial lipid responses do not differ following consumption of butter or
      vegetable oil when consumed with omega-3 polyunsaturated fatty acids.
AB  - Dietary saturated fat (SFA) intake has been associated with elevated blood lipid
      levels and increased risk for the development of chronic diseases. However, some
      animal studies have demonstrated that dietary SFA may not raise blood lipid
      levels when the diet is sufficient in omega-3 polyunsaturated fatty acids (n
      3PUFA). Therefore, in a randomised cross-over design, we investigated the
      postprandial effects of feeding meals rich in either SFA (butter) or vegetable
      oil rich in omega-6 polyunsaturated fatty acids (n-6PUFA), in conjunction with n
      3PUFA, on blood lipid profiles [total cholesterol, low density lipoprotein
      cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C) and
      triacylglycerol (TAG)] and n-3PUFA incorporation into plasma lipids over a 6-h
      period. The incremental area under the curve for plasma cholesterol, LDL-C, HDL
      C, TAG and n-3PUFA levels over 6 h was similar in the n-6PUFA compared to SFA
      group. The postprandial lipemic response to saturated fat is comparable to that
      of n-6PUFA when consumed with n-3PUFA; however, sex-differences in response to
      dietary fat type are worthy of further attention. 

PMID- 25753896
TI  - RNAi targeting putative genes in phosphatidylcholine turnover results in
      significant change in fatty acid composition in Crambe abyssinica seed oil.
AB  - The aim of this study was to evaluate the importance of three enzymes, LPCAT,
      PDCT and PDAT, involved in acyl turnover in phosphatidylcholine in order to
      explore the possibility of further increasing erucic acid (22:1) content in
      Crambe seed oil. The complete coding sequences of LPCAT1-1 and LPCAT1-2 encoding
      lysophosphatidylcholine acyltransferase (LPCAT), PDCT1 and PDCT2 encoding
      phosphatidylcholine:diacylglycerol cholinephosphotransferase (PDCT), and PDAT
      encoding phospholipid:diacylglycerol acyltransferase (PDAT) were cloned from
      developing Crambe seeds. The alignment of deduced amino acid sequences displayed
      a high similarity to the Arabidopsis homologs. Transgenic lines expressing RNA
      interference (RNAi) targeting either single or double genes showed significant
      changes in the fatty acid composition of seed oil. An increase in oleic acid
      (18:1) was observed, to varying degrees, in all of the transgenic lines, and a
      cumulative effect of increased 18:1 was shown in the LPCAT-PDCT double-gene RNAi.
      However, LPCAT single-gene RNAi led to a decrease in 22:1 accumulation, while
      PDCT or PDAT single-gene RNAi had no obvious effect on the level of 22:1. In
      agreement with the abovementioned oil phenotypes, the transcript levels of the
      target genes in these transgenic lines were generally reduced compared to wild
      type levels. In this paper, we discuss the potential to further increase the 22:1
      content in Crambe seed oil through downregulation of these genes in combination
      with fatty acid elongase and desaturases. 

PMID- 25753897
TI  - Feasibility and effectiveness of two community-based HIV testing models in rural
      Swaziland.
AB  - OBJECTIVES: To evaluate the feasibility (population reached, costs) and
      effectiveness (positivity rates, linkage to care) of two strategies of community
      based HIV testing and counselling (HTC) in rural Swaziland. METHODS: Strategies
      used were mobile HTC (MHTC) and home-based HTC (HBHTC). Information on age, sex,
      previous testing and HIV results was obtained from routine HTC records. A
      consecutive series of individuals testing HIV-positive were followed up for 6
      months from the test date to assess linkage to care. RESULTS: A total of 9 060
      people were tested: 2 034 through MHTC and 7 026 through HBHTC. A higher
      proportion of children and adolescents (<20 years) were tested through HBHTC than
      MHTC (57% vs. 17%; P < 0.001). MHTC reached a higher proportion of adult men than
      HBHTC (42% vs. 39%; P = 0.015). Of 398 HIV-positive individuals, only 135 (34%)
      were enrolled in HIV care within 6 months. Of 42 individuals eligible for
      antiretroviral therapy, 22 (52%) started treatment within 6 months. Linkage to
      care was lowest among people who had tested previously and those aged 20-40
      years. HBHTC was 50% cheaper (US$11 per person tested; $797 per individual
      enrolled in HIV care) than MHTC ($24 and $1698, respectively). CONCLUSION: In
      this high HIV prevalence setting, a community-based testing programme achieved
      high uptake of testing and appears to be an effective and affordable way to
      encourage large numbers of people to learn their HIV status (particularly
      underserved populations such as men and young people). However, for community HTC
      to impact mortality and incidence, strategies need to be implemented to ensure
      people testing HIV-positive in the community are linked to HIV care.

PMID- 25753898
TI  - Release from endoplasmic reticulum matrix proteins controls cell surface
      transport of MHC class I molecules.
AB  - The anterograde transport of secretory proteins from the endoplasmic reticulum
      (ER) to the plasma membrane is a multi-step process. Secretory proteins differ
      greatly in their transport rates to the cell surface, but the contribution of
      each individual step to this difference is poorly understood. Transport rates may
      be determined by protein folding, chaperone association in the ER, access to ER
      exit sites (ERES) and retrieval from the ER-Golgi intermediate compartment or the
      cis-Golgi to the ER. We have used a combination of folding and trafficking assays
      to identify the differential step in the cell surface transport of two natural
      allotypes of the murine major histocompatibility complex (MHC) class I peptide
      receptor, H-2D(b) and H-2K(b) . We find that a novel pre-ER exit process that
      acts on the folded lumenal part of MHC class I molecules and that drastically
      limits their access to ERES accounts for the transport difference of the two
      allotypes. Our observations support a model in which the cell surface transport
      of MHC class I molecules and other type I transmembrane proteins is governed by
      the affinity of all their folding and maturation states to the proteins of the ER
      matrix. 

PMID- 25753899
TI  - The relationship between prostate-specific antigen and TNM classification or
      Gleason score in prostate cancer patients with low prostate-specific antigen
      levels.
AB  - BACKGROUND: Prostate-specific antigen (PSA) is a useful biomarker for risk
      classification in patients with prostate cancer. However, it is unclear whether a
      correlation exists between low PSA levels (<10 ng/ml) at diagnosis and prognosis.
      METHODS: Of the 642 Japanese patients who underwent prostate biopsy and were
      diagnosed with prostate cancer at Kanazawa University Hospital from 2000 to 2010,
      406 patients with a PSA level <20 ng/ml were retrospectively reviewed. RESULTS:
      PSA levels in 275 (68%) patients were <10 ng/ml. Although the percentage of
      Gleason score 8-10 in patients with a PSA level of <3.5 ng/ml was higher than
      that in patients with a PSA level between 3.5 and 10 ng/ml, it was not
      statistically significant. On the other hand, the percentage of higher stage (T3
      and T4) patients with a PSA level <3.5 ng/ml was significantly greater than that
      in patients with a PSA level between 3.5 and 10 ng/ml (P < 0.0001). The
      percentage of metastases (N1 and M1) in patients with a PSA level <3.5 ng/ml was
      also significantly higher than that in patients with a PSA level between 3.5 and
      10 ng/ml (P = 0.0112). CONCLUSIONS: Patients with prostate cancer with a PSA
      level <3.5 ng/ml at diagnosis had a more advanced stage of cancer compared with
      those with a PSA level between 3.5 and 10 ng/ml. Therefore, risk classification
      using PSA levels at diagnosis may need to take into consideration this specific
      PSA range in order to better predict survival.

PMID- 25753900
TI  - Frozen section during partial nephrectomy: does it predict positive margins?
AB  - OBJECTIVE: To investigate the clinical utility of frozen section (FS) analysis
      performed during partial nephrectomy (PN) and its influence on intra-operative
      management. PATIENTS AND METHODS: We performed a retrospective analysis of
      consecutive PN cases from 2010 to 2013. We evaluated the concordance between the
      intra-operative FS diagnosis and the FS control diagnosis, a postoperative
      quality assurance measure performed on all FS diagnoses after formalin fixation
      of the tissue. We also evaluated the concordance between the intra-operative FS
      diagnosis and the final specimen margin. Operating reports were reviewed for
      change in intra-operative management for cases with a positive or atypia FS
      diagnosis, or if the mass was sent for FS. RESULTS: A total of 576 intra
      operative FSs were performed in 351 cases to assess the PN tumour bed margin, 19
      (5.4%) of which also had a mass sent for FS to assess the tumour type. The
      concordance rate between the FS diagnosis and the FS control diagnosis was 98.3%.
      There were 30 (8.5%) final positive specimen margins, of which four (13.3%) were
      classified as atypia, 17 (56.7%) as negative and nine (30%) as positive on FS
      diagnosis. Intra-operative management was influenced in six of nine cases with a
      positive FS diagnosis and in one of nine cases with an FS diagnosis of atypia.
      CONCLUSIONS: The relatively high false-negative rate, controversy over the
      prognosis of a positive margin, and inconsistency in influencing intra-operative
      management are arguments against the routine use of FS in PN cases.

PMID- 25753901
TI  - Use of the Hospital Anxiety and Depression Scale in Spanish caregivers.
AB  - BACKGROUND: The Hospital Anxiety and Depression Scale (HADS) is widely used in
      the assessment of anxiety and depression, but there are scarce data about its
      psychometric properties in caregivers of older relatives. OBJECTIVE: The goal of
      this study was to analyse the factor structure of the HADS to verify its
      suitability to assess emotional symptomatology in family caregivers of old
      people, its internal consistency and confirming its relation with the General
      Health Questionnaire (GHQ-12) and an index of disease and physical complaints.
      METHODS: One hundred and seventy-five family caregivers (25 men and 150 women)
      aged 32-86, who were taking care of at least one older person in a situation of
      dependence, were recruited for this study. A descriptive, comparative,
      correlational design was employed. The scientific adequacy of the questionnaire
      and its structure were analysed using confirmatory factor analysis. The scores
      obtained in the GHQ and in an index of disease and physical complaints were used
      as external criteria to assess the adequacy of the HADS for caregivers. RESULTS:
      Higher levels of anxiety and depression than in the normal population were
      obtained. The reliability/internal validity of the questionnaire was adequate. A
      bifactor model, with one subscale for anxiety and one for depression, provides
      the best fit to the data. The subscales were related to GHQ-12 and index of
      diseases/physical complaints. CONCLUSIONS: The HADS was shown to be useful to
      assess the presence of anxiety and depression in family caregivers, and the
      original two-dimensional model is the most adequate.

PMID- 25753902
TI  - Ideomotor feedback control in a recurrent neural network.
AB  - The architecture of a neural network controlling an unknown environment is
      presented. It is based on a randomly connected recurrent neural network from
      which both perception and action are simultaneously read and fed back. There are
      two concurrent learning rules implementing a sort of ideomotor control: (i)
      perception is learned along the principle that the network should predict
      reliably its incoming stimuli; (ii) action is learned along the principle that
      the prediction of the network should match a target time series. The coherent
      behavior of the neural network in its environment is a consequence of the
      interaction between the two principles. Numerical simulations show a promising
      performance of the approach, which can be turned into a local and better
      "biologically plausible" algorithm. 

PMID- 25753903
TI  - A small-world-based population encoding model of the primary visual cortex.
AB  - A wide range of evidence has shown that information encoding performed by the
      visual cortex involves complex activities of neuronal populations. However, the
      effects of the neuronal connectivity structure on the population's encoding
      performance remain poorly understood. In this paper, a small-world-based
      population encoding model of the primary visual cortex (V1) is established on the
      basis of the generalized linear model (GLM) to describe the computation of the
      neuronal population. The model mainly consists of three sets of filters,
      including a spatiotemporal stimulus filter, a post-spike history filter, and a
      set of coupled filters with the coupling neurons organizing as a small-world
      network. The parameters of the model were fitted with neuronal data of the rat V1
      recorded with a micro-electrode array. Compared to the traditional GLM, without
      considering the small-world structure of the neuronal population, the proposed
      model was proved to produce more accurate spiking response to grating stimuli and
      enhance the capability of the neuronal population to carry information. The
      comparison results proved the validity of the proposed model and further suggest
      the role of small-world structure in the encoding performance of local
      populations in V1, which provides new insights for understanding encoding
      mechanisms of a small scale population in visual system. 

PMID- 25753904
TI  - A recyclable heavy fluorous tag carrying an allyl alcohol pendant group: design
      and evaluation toward applications in synthetic carbohydrate chemistry.
AB  - Toward applications in synthetic carbohydrate chemistry, we converted our
      previous acid-resistant heavy fluorous tag [(Rf)3C-CH2-OH, 1] to allyl alcohol
      derivatives [(Rf)3C-CH2-O-(CH2)n-CH=CH-CH2-OH, 3 (n=1) or 4 (n=3)] by means of
      olefin cross metathesis. They were then subjected to beta-glycosylation reactions
      by using a series of glycosyl donors, including glycosyl bromide and
      trichloroacetimidates. The terminal OH group in 3 and 4 was found to be beta
      glycosylated in moderate yield when 2,3,4,6-tetra-O-benzoyl-D-galactosyl
      trichloroacetimidate was used as the glycosyl donor. Upon a detachment reaction
      using Pd(PPh3)4, the initial heavy fluorous tag 1 was recovered in high yield
      (>90%) together with 1-hydroxy sugar, indicating that not only the allyl ether
      linkage in the glycosides but also the internal di-alkyl ether linkage in 4 be
      cleaved by the action of the Pd-catalyst enabling long-range olefin
      transmigration. Potential utility was demonstrated by using the tetra-O-benzoyl
      beta-D-galactosylated derivative of 3 in a series of deprotection, protection and
      glycosylation reactions, which were conductible in high yields without using
      chromatographic purification process. These findings prompt us to propose a
      general scheme in which the acid-resistant heavy fluorous compound 1 is applied
      as a recyclable tag in synthetic carbohydrate chemistry.

PMID- 25753905
TI  - Analog time-reversed ultrasonically encoded light focusing inside scattering
      media with a 33,000* optical power gain.
AB  - Recent breakthrough in wavefront engineering shows great promises in controlling
      light propagation inside scattering media. At present, the digital approaches
      enjoy high gain, while their speeds are slow because of high data throughputs. In
      contrast, the analog approaches are intrinsically fast but suffer from poor
      efficiencies and small gains. Further improvements in both speed and gain are
      necessary to advance the existing technologies toward real-world applications.
      Here, we report analog time-reversal of acousto-optically tagged photons with a
      flux amplification of over 33,000 times (45 dB) at a target location inside
      scattering media. Such a substantial power gain enhancement is achieved when the
      temporal width of the time-reversed photon packet is squeezed below the carrier
      recombination-limited hologram decay time in a photorefractive crystal. Despite a
      focusing energy gain below unity, the unprecedented power gain is expected to
      enable new optical imaging, sensing, manipulation and treatment applications. 

PMID- 25753906
TI  - Transcranial magnetic stimulation follow-up study in early Parkinson's disease: A
      decline in compensation with disease progression?
AB  - BACKGROUND: A number of neurophysiological abnormalities have been described in
      patients with Parkinson's disease, but very few longitudinal studies of how these
      change with disease progression have been reported. We describe measures of motor
      cortex inhibition and plasticity at 6 and 12 mo in 12 patients that we previously
      reported at initial diagnosis. Given the well-known interindividual variation in
      these measures, we were particularly concerned with the within-subject changes
      over time. METHODS: Patients were assessed clinically, and transcranial magnetic
      stimulation (TMS) was used to measure motor cortical excitability, inhibition
      (short interval intracortical inhibition, cortical silent period), and plasticity
      (response to excitatory paired associative stimulation protocol) in both
      hemispheres. All measurements were performed 6 mo and 12 mo after the baseline
      experiments. RESULTS: Asymmetry in clinical motor symptoms was reflected in
      asymmetry of plasticity and inhibition. In the group as a whole, little change
      was seen in any of the parameters over 12 mo. However, analysis of within
      individual data showed clear correlations between changes in clinical asymmetry
      and asymmetry of response to paired associative stimulation protocol and cortical
      silent period. CONCLUSIONS: Longitudinal changes in cortical silent period and
      response to paired associative stimulation protocol in Parkinson's disease
      reflect dynamic effects on motor cortex that are related to progression of motor
      signs. They are useful objective markers of early disease progression that could
      be used to detect effects of disease-modifying therapies. The decline in
      heightened plasticity that was present at disease onset may reflect failure of
      compensatory mechanisms that maintained function in the preclinical state.

PMID- 25753907
TI  - Involvement of cortico-subcortical circuits in normoacousic chronic tinnitus: A
      source localization EEG study.
AB  - OBJECTIVE: To better characterize brain circuits dysfunctions in normoacousic
      tinnitus sufferers. METHODS: 17 normoacousic chronic, unilateral high-pitched
      tinnitus sufferers (6 females, 43.6 +/- 9.8 y.o, disease duration 22 +/- 35
      months) underwent a 29-channel resting-state electroencephalography (EEG - 5 min
      opened-eyes, 5 min closed-eyes) and auditory oddball paradigm for event-related
      potentials analyses (ERPs - N1, P2 and P300). Cortical 3D distribution of current
      source density was computed with sLORETA. Results were compared with 17 controls
      (9 females, 45.7 +/- 15.1 y.o). RESULTS: Eyes opened, tinnitus sufferers had
      lower alpha and beta sources in the left inferior parietal lobule. Eyes closed,
      tinnitus sufferers had decreased alpha sources in the left inferior temporal and
      post-central gyri, and low gamma sources in the left middle temporal gyrus. EEG
      data did not correlate with tinnitus sufferers' clinical features. Subjects with
      tinnitus had shorter N1 and P2 latencies. P300 did not differ between groups.
      sLORETA solutions showed decreased sources of these ERPs in the left inferior
      temporal gyrus in the tinnitus group. CONCLUSIONS: We showed cortico-thalamo
      cortical involvements in normoacousic tinnitus with hyperexcitability of the left
      auditory cortex and inferior temporal gyrus. SIGNIFICANCE: This might reflect
      processes of maladaptive cortical plasticity and memory consolidation. Further
      validation is needed to establish the value of this tool in customizing
      therapeutic approach.

PMID- 25753908
TI  - The risk of tuberculosis in patients with psoriasis treated with anti-tumor
      necrosis factor agents.
AB  - BACKGROUND: Tumor necrosis factor-alpha (TNF-alpha) antagonist treatment is
      associated with 1.6 to 27 times higher risk of tuberculosis (TB). OBJECTIVE: To
      find TB incidence of psoriasis patients treated with TNF- alpha antagonists and
      define risk factors related with this condition in a country with moderately high
      risk of TB. METHODS: Three hundred seventy psoriasis patients treated by anti-TNF
      agents in four referral centers were included. The data on the characteristics of
      the patients, TB history, tuberculosis skin test results, anti-TNF agent type and
      exposure time, localization of TB, and isoniazide prophylaxis state were
      analyzed. RESULTS: Four patients (1.08%) developed TB, three pulmonary and one
      gastrointestinal, 2-23 months after initiating anti-TNF agents. Other than the
      patient with gastrointestinal TB, who was using methotrexate and corticosteroid
      concomitantly, none had contributing risk factors for TB. Two patients developed
      pulmonary TB in spite of chemoprophylaxis. Three patients with pulmonary TB
      completely recovered following antiTB treatment whereas patients with
      gastroinrestinal TB developed renal failure. LIMITATIONS: The major limitation of
      the study is the lack of a diseased control group, which enables us to compare
      the risk of psoriatics with that of patients having other inflammatory diseases.
      CONCLUSION: Tuberculosis is a rare but a severe complication of anti-TNF
      treatment and may develop in spite of chemoprophylaxis. The risk of TB in
      psoriasis patients in the present study is comparable to literature mostly based
      on rheumatology patients.

PMID- 25753909
TI  - Facial spicules and pink papules in a renal transplant recipient.

PMID- 25753910
TI  - Medical consultation the year before melanoma diagnosis: could we detect melanoma
      earlier?

PMID- 25753911
TI  - Reliable and cost-effective approach for diagnosis of heterozygous F8/F9 large
      deletions by quantitative real-time PCR.

PMID- 25753912
TI  - Predictability of multispecies competitive interactions in three populations of
      Atlantic salmon Salmo salar.
AB  - Juvenile Atlantic salmon Salmo salar from three allopatric populations (LaHave,
      Sebago and Saint-Jean) were placed into artificial streams with combinations of
      four non-native salmonids: brown trout Salmo trutta, rainbow trout Oncorhynchus
      mykiss, Chinook salmon Oncorhynchus tshawytscha and coho salmon Oncorhynchus
      kisutch. Non-additive effects, as evidenced by lower performance than predicted
      from weighted summed two-species competition trials, were detected for S. salar
      fork length (LF ) and mass, but not for survival, condition factor or riffle use.
      These data support emerging theory on niche overlap and species richness as
      factors that can lead to non-additive competition effects. 

PMID- 25753913
TI  - Niche partitioning in arbuscular mycorrhizal communities in temperate grasslands:
      a lesson from adjacent serpentine and nonserpentine habitats.
AB  - Arbuscular mycorrhizal fungi (AMF) represent an important soil microbial group
      playing a fundamental role in many terrestrial ecosystems. We explored the
      effects of deterministic (soil characteristics, host plant life stage,
      neighbouring plant communities) and stochastic processes on AMF colonization,
      richness and community composition in roots of Knautia arvensis (Dipsacaceae)
      plants from three serpentine grasslands and adjacent nonserpentine sites.
      Methodically, the study was based on 454-sequencing of the ITS region of rDNA. In
      total, we detected 81 molecular taxonomical operational units (MOTUs) belonging
      to the Glomeromycota. Serpentine character of the site negatively influenced AMF
      root colonization, similarly as higher Fe concentration. AMF MOTUs richness
      linearly increased along a pH gradient from 3.5 to 5.8. Contrary, K and Cr soil
      concentration had a negative influence on AMF MOTUs richness. We also detected a
      strong relation between neighbouring plant community composition and AMF MOTUs
      richness. Although spatial distance between the sampled sites (c. 0.3-3 km)
      contributed to structuring AMF communities in K. arvensis roots, environmental
      parameters were key factors in this respect. In particular, the composition of
      AMF communities was shaped by the complex of serpentine conditions, pH and
      available soil Ni concentration. The composition of AMF communities was also
      dependent on host plant life stage (vegetative vs. generative). Our study
      supports the dominance of deterministic factors in structuring AMF communities in
      heterogeneous environment composed of an edaphic mosaic of serpentine and
      nonserpentine soils.

PMID- 25753914
TI  - Circulating betatrophin is elevated in patients with type 1 and type 2 diabetes.
AB  - There is evidence that betatrophin, a hormone derived from adipose tissue and
      liver, affects the proliferation of pancreatic beta cells in mice. The aim of
      this study was to examine circulating betatrophin concentrations in Japanese
      healthy controls and patients with type 1 and type 2 diabetes. A total of 76
      subjects (12 healthy controls, 34 type 1 diabetes, 30 type 2 diabetes) were
      enrolled in the study. Circulating betatrophin was measured with an ELISA kit and
      clinical parameters related to betatrophin were analyzed statistically.
      Circulating betatrophin (Log transformed) was significantly increased in patients
      with diabetes compared with healthy subjects (healthy controls, 2.29 +/- 0.51;
      type 1 diabetes, 2.94 +/- 0.44; type 2 diabetes, 3.17 +/- 0.18; p<0.001, 4.1 to
      5.4 times in pg/mL order). Age, HbA1c, fasting plasma glucose and Log
      triglyceride were strongly associated with Log betatrophin in all subjects (n=76)
      in correlation analysis. In type 1 diabetes, there was a correlation between Log
      betatrophin and Log CPR. These results provide the first evidence that
      circulating betatrophin is significantly elevated in Japanese patients with
      diabetes. The findings of this pilot study also suggest a possibility of
      association between the level of betatrophin and the levels of glucose and
      triglycerides. 

PMID- 25753915
TI  - Hyperinsulinemic hypoglycemia syndrome associated with mutations in the human
      insulin receptor gene: report of two cases.
AB  - Insulinoma and insulin or insulin receptor (IR) autoantibodies are the main
      causes of hyperinsulinemic hypoglycemia in adults, but the exact cause in other
      cases remains obscure. This study is to determine the genetic basis of
      hyperinsulinemic hypoglycemia in two cases without the above abnormalities.
      Sequence analysis of IR gene in two patients with adult-onset hyperinsulinemic
      hypoglycemia and their relatives were performed, and the mutant gene observed in
      one case was analyzed. Both cases had normal levels of fasting plasma glucose
      (FPG), fasting hyperinsulinemia, low insulin sensitivity, and hypoglycemia with
      excessive insulin secretion during oral glucose tolerance test (OGTT). Both
      reported adult-onset postprandial hypoglycemic symptoms. In one patient, a
      missense mutation (Arg256Cys) was detected in both alleles of the IR gene, and
      his parents had the same mutation in only one allele but no hypoglycemia. The
      other had a novel nonsense mutation (Trp1273X) followed by a mutation
      (Gln1274Lys) in one allele, and his 9-year old son had the same mutation in one
      allele, together with hyperinsulinemic hypoglycemia during OGTT. Overexpression
      experiments of the mutant gene found in Case 1 in mammalian cells showed abnormal
      processing of the IR protein and demonstrated reduced function of Akt/Erk
      phosphorylation by insulin in the cells. In two cases of hyperinsulinemic
      hypoglycemia in adults, we found novel mutations in IR gene considered to be
      linked to hypoglycemia. We propose a disease entity of adult-onset
      hyperinsulinemic hypoglycemia syndrome associated with mutations in IR gene.

PMID- 25753916
TI  - Practical synthesis of [n]cycloparaphenylenes (n = 5, 7-12) by H2SnCl4-mediated
      aromatization of 1,4-dihydroxycyclo-2,5-diene precursors.
AB  - Cyclic precursors of cycloparaphenylenes (CPPs) containing 1,4-dihydroxy-2,5
      cyclohexadien-1,4-diyl units are prepared by modifying a synthetic method
      developed by Jasti and co-workers for the synthesis of corresponding 1,4
      dimethoxy derivatives. Reductive aromatization of the diyl moieties by SnCl2/2
      HCl takes place under mild conditions and affords the CPPs in good yields,
      incorporating 5 or 7-12 phenylene units. Highly strained [5]CPP is synthesized in
      greater than 0.3 g scale. (119)Sn NMR spectroscopy clarifies the in situ
      formation of an ate complex, H2SnCl4, upon mixing a 2:1 ratio of HCl and SnCl2,
      which serves as a highly active reducing agent under nearly neutral conditions.
      When more than 2 equivalents of HCl, in relation to SnCl2, are used, acid
      catalyzed decomposition of the CPP precursors takes place. The stoichiometry of
      HCl and SnCl2 is critical in achieving the desired aromatization reaction of
      highly strained CPP precursors.

PMID- 25753917
TI  - The new insights into the oyster antimicrobial defense: Cellular, molecular and
      genetic view.
AB  - Oysters are sessile filter feeders that live in close association with abundant
      and diverse communities of microorganisms that form the oyster microbiota. In
      such an association, cellular and molecular mechanisms have evolved to maintain
      oyster homeostasis upon stressful conditions including infection and changing
      environments. We give here cellular and molecular insights into the Crassostrea
      gigas antimicrobial defense system with focus on antimicrobial peptides and
      proteins (AMPs). This review highlights the central role of the hemocytes in the
      modulation and control of oyster antimicrobial response. As vehicles for AMPs and
      other antimicrobial effectors, including reactive oxygen species (ROS), and
      together with epithelia, hemocytes provide the oyster with local defense
      reactions instead of systemic humoral ones. These reactions are largely based on
      phagocytosis but also, as recently described, on the extracellular release of
      antimicrobial histones (ETosis) which is triggered by ROS. Thus, ROS can signal
      danger and activate cellular responses in the oyster. From the current
      literature, AMP production/release could serve similar functions. We provide also
      new lights on the oyster genetic background that underlies a great diversity of
      AMP sequences but also an extraordinary individual polymorphism of AMP gene
      expression. We discuss here how this polymorphism could generate new immune
      functions, new pathogen resistances or support individual adaptation to
      environmental stresses. 

PMID- 25753918
TI  - Modest weight loss through a 12-week weight management program with behavioral
      modification seems to attenuate inflammatory responses in young obese Koreans.
AB  - Obesity has been reported to impair immune functions and lead to low-grade long
      term inflammation; however, studies that have investigated the impact of weight
      loss on these among the young and slightly obese are limited. Thus, we
      investigated the effect of a 12-week weight management program with behavioral
      modifications on cell-mediated immune functions and inflammatory responses in
      young obese participants. Our hypothesis was that weight loss would result in
      improved immune functions and decreased inflammatory responses. Sixty-four
      participants (45 obese and 19 normal weight) finished the program. Obese (body
      mass index >=25) participants took part in 5 group education and 6 individual
      counseling sessions. Normal-weight (body mass index 18.5-23) participants only
      attended 6 individual sessions. The goal for the obese was to lose 0.5 kg/wk by
      reducing their intake by 300 to 500 kcal/d and increasing their physical
      activity. Program participation resulted in a modest but significant decrease in
      weight (2.7 +/- 0.4 kg, P < .001) and lipopolysaccharide-stimulated interleukin
      1beta production (from 0.85 +/- 0.07 to 0.67 +/- 0.07 ng/mL, P < .05) in the
      obese. In the obese group, increase in phytohemagglutinin-stimulated interleukin
      10 production, a TH2 and anti-inflammatory cytokine, approached significance
      after program participation (from 6181 +/- 475 to 6970 +/- 632 pg/mL, P = .06).
      No significant changes in proliferative responses to the optimal concentration of
      concanavalin A or phytohemagglutinin were observed in the obese after program
      participation. Collectively, modest weight loss did not change the cell-mediated
      immune functions significantly but did attenuate the inflammatory response in
      young and otherwise healthy obese adults. 

PMID- 25753919
TI  - Dietary protein intake is associated with maximal and explosive strength of the
      leg flexors in young and older blue collar workers.
AB  - The aim of this study was to investigate the association between dietary protein
      (PRO) intake and maximal and rapid strength of the leg flexors in blue collar
      (BC) working men. Twenty-four young (age, 23.2 +/- 2.1 years) and 19 older (age,
      52.8 +/- 5.2 years) men employed in BC occupations completed a 3-day dietary
      record and isometric strength testing of the leg flexors. Food logs were analyzed
      for total PRO (TPRO) and essential amino acid (EAA) intake. Rapid and maximal
      strength capacities were examined from the rate of torque development at 50
      milliseconds and peak torque of the torque-time curves, respectively. Pearson
      correlations and partial correlations were used to examine the relationships
      between TPRO and EAA intake on strength variables. Peak torque was positively
      correlated to TPRO and EAA intake in the young (r = 0.439 and r = 0.431; P < .05)
      and older (r = 0.636 and r = 0.605; P < .01) men, and rate of torque development
      at 50 milliseconds was correlated to TPRO and EAA intake in the young (r = 0.512
      and r = 0.310; P = .01) and older (r = 0.662 and r = 0.665; P < .01) men,
      respectively. There were no relationships (P > .05) between TPRO and strength
      variables when controlling for EAA intake. Total PRO intake explained 20 to 44%
      of the variance in rapid and maximal strength for both age groups. Essential
      amino acid intake was largely responsible for the positive relationship between
      PRO intake and strength. Across young and older BC working male populations, PRO
      consumption was associated with both maximal and explosive strength capacities of
      the leg flexors muscle group. 

PMID- 25753920
TI  - Identifying the causes of sediment-associated toxicity in urban waterways in
      South China: incorporating bioavailabillity-based measurements into whole
      sediment toxicity identification evaluation.
AB  - Sediments in urban waterways of Guangzhou, China, were contaminated by a variety
      of chemicals and showed prevalent toxicity to benthic organisms. A combination of
      whole-sediment toxicity identification evaluation (TIE) and bioavailability-based
      extraction was used to identify the causes of sediment toxicity. Of the 6
      sediment samples collected, 4 caused 100% mortality to Chironomus dilutus in 10-d
      bioassays, and the potential toxicants were assessed using TIE in these sediments
      after dilution. The results of phase I characterization showed that organic
      contaminants were the principal contributors to the mortality of the midges in 2
      sediments and that metals and organics jointly caused the mortality in the other
      2 sediments. Ammonia played no role in the mortality for any samples.
      Conventional toxic unit analysis in phase II testing identified Cr, Cu, Ni, Pb,
      and Zn as the toxic metals, with cypermethrin, lambda-cyhalothrin, deltamethrin,
      and fipronils being the toxic organics. To improve the accuracy of identifying
      the toxicants, 4-step sequential extraction and Tenax extraction were conducted
      to analyze the bioavailability of the metals and organics, respectively.
      Bioavailable toxic unit analysis narrowed the list of toxic contributors, and the
      putative toxicants included 3 metals (Zn, Ni, and Pb) and 3 pesticides
      (cypermethrin, lambda-cyhalothrin, and fipronils). Metals contributed to the
      mortality in all sediments, but sediment dilution reduced the toxicity and
      confounded the characterization of toxicity contribution from metals in 2
      sediments in phase I. Incorporating bioavailability-based measurements into whole
      sediment TIE improved the accuracy of identifying the causative toxicants in
      urban waterways where multiple stressors occurred and contributed to sediment
      toxicity jointly.

PMID- 25753921
TI  - Inhibition of protein synthesis leading to unfolded protein response is the major
      event in abrin-mediated apoptosis.
AB  - Abrin obtained from the plant Abrus precatorius inhibits protein synthesis and
      also triggers apoptosis in cells. Previous studies from our laboratory suggested
      a link between these two events. Using an active site mutant of abrin A-chain
      which exhibits 225-fold lower protein synthesis inhibitory activity than the wild
      type abrin A-chain, we demonstrate in this study that inhibition of protein
      synthesis induced by abrin is the major factor triggering unfolded protein
      response leading to apoptosis. Since abrin A-chain requires the B-chain for
      internalization into cells, the wild-type and mutant recombinant abrin A-chains
      were conjugated to native ricin B-chain to generate hybrid toxins, and the toxic
      effects of the two conjugates were compared. The rate of inhibition of protein
      synthesis mediated by the mutant ricin B-rABRA (R167L) conjugate was slower than
      that of the wild-type ricin B-rABRA conjugate as expected. The mutant conjugate
      activated p38MAPK and caspase-3 similar to its wild-type counterpart although at
      later time points. Overall, these results confirm that inhibition of protein
      synthesis is the major event contributing to abrin-mediated apoptosis. 

PMID- 25753922
TI  - Rac1 is a novel interactor of Drosophila guanine nucleotide exchange factor
      GEFmeso.
AB  - Guanine nucleotide exchange factors (GEF) are proteins that regulate the activity
      of GTPases by catalysing the exchange of GDP for GTP. In this work, we studied
      the interaction of various Rho family GTPases CDC42, Rac1 and RhoA with GEFmeso,
      a GEF expressed in Drosophila melanogaster (fruit fly). The interaction of
      GEFmeso with Rho family GTPases was studied by means of guanine nucleotide
      exchange assays. Our results suggest that GEFmeso interacts with Rac1 in addition
      to its interaction with CDC42 and Ral, which was reported earlier. We propose
      that the guanine nucleotide exchange factor GEFmeso is involved in a
      developmental process that requires the synergistic action of CDC42 and Rac1
      during Drosophila development.

PMID- 25753923
TI  - Weight loss experiences of obese perimenopausal women with metabolic syndrome.
AB  - AIMS AND OBJECTIVES: To develop a descriptive theory for the weight loss
      experiences of obese perimenopausal women with metabolic syndrome. BACKGROUND:
      Obesity and metabolic syndrome both pose a threat to the health of perimenopausal
      women; therefore, understanding perimenopausal women's subjective feelings and
      experiences is beneficial to establishing effective prevention strategies.
      However, studies have rarely explored these relevant experiences. DESIGN: A
      qualitative study using the grounded theory method to establish a descriptive
      theory. METHODS: Eighteen obese perimenopausal women with metabolic syndrome aged
      45-60 years participated in comprehensive interviews. RESULTS: 'Crossing the gaps
      to making life modifications' was the core category, and 'the awareness of weight
      gain and health alarm' was the antecedent condition. In the weight loss
      experience, the following three interaction categories were identified: (1)
      'experiencing bad feelings,' (2) 'encountering obstacles' and (3) 'making efforts
      to transition to a new life.' Some women adhered to new life habits through
      perceiving social support and by using self-incentives. Finally, women enjoyed
      and mastered self-monitoring of their health in their new life, and practiced new
      changes as part of their life. However, some participants felt that making
      changes to their life was too time-consuming. Therefore, these women chose to
      live with their abnormal health without making changes. CONCLUSIONS: Obese
      perimenopausal women with metabolic syndrome experienced various gaps in their
      weight loss process. Although they struggled with many obstacles, these women
      were able to learn from their experiences and face their health challenges.
      RELEVANCE TO CLINICAL PRACTICE: These findings can guide healthcare professionals
      to provide appropriate interventions to understand the hidden health problems of
      this particular group of women. Healthcare professionals should develop a set of
      plans by which women receive a complete weight loss program and support from
      professionals and family.

PMID- 25753924
TI  - Ten-year blood pressure trajectories, cardiovascular mortality, and life years
      lost in 2 extinction cohorts: the Minnesota Business and Professional Men Study
      and the Zutphen Study.
AB  - BACKGROUND: Blood pressure (BP) trajectories derived from measurements repeated
      over years have low measurement error and may improve cardiovascular disease
      prediction compared to single, average, and usual BP (single BP adjusted for
      regression dilution). We characterized 10-year BP trajectories and examined their
      association with cardiovascular mortality, all-cause mortality, and life years
      lost. METHODS AND RESULTS: Data from 2 prospective and nearly extinct cohorts of
      middle-aged men-the Minnesota Business and Professional Men Study (n=261) and the
      Zutphen Study (n=632)-were used. BP was measured annually during 1947-1957 in
      Minnesota and 1960-1970 in Zutphen. BP trajectories were identified by latent
      mixture modeling. Cox proportional hazards and linear regression models examined
      BP trajectories with cardiovascular mortality, all-cause mortality, and life
      years lost. Associations were adjusted for age, serum cholesterol, smoking, and
      diabetes mellitus. Mean initial age was about 50 years in both cohorts. After 10
      years of BP measurements, men were followed until death on average 20 years
      later. All Minnesota men and 98% of Zutphen men died. Four BP trajectories were
      identified, in which mean systolic BP increased by 5 to 49 mm Hg in Minnesota and
      5 to 20 mm Hg in Zutphen between age 50 and 60. The third systolic BP
      trajectories were associated with 2 to 4 times higher cardiovascular mortality
      risk, 2 times higher all-cause mortality risk, and 4 to 8 life years lost,
      compared to the first trajectory. CONCLUSIONS: Ten-year BP trajectories were the
      strongest predictors, among different BP measures, of cardiovascular mortality,
      all-cause mortality, and life years lost in Minnesota. However, average BP was
      the strongest predictor in Zutphen.

PMID- 25753925
TI  - Myelopoiesis dysregulation associated to sustained APRIL production in multiple
      myeloma-infiltrated bone marrow.
AB  - Multiple myeloma (MM) is a non-curable tumor developing in the bone marrow (BM).
      The BM microenvironment rich in hematopoietic precursors is suspected to have a
      role in MM development. Here we show that a proliferation-inducing ligand (APRIL)
      mediated in vivo MM promotion. In MM-infiltrated BM, APRIL originated from
      differentiating myeloid cells with an expression peak in precursor cells.
      Notably, APRIL expression stayed stable in BM despite MM infiltration. The pool
      of APRIL-producing cells changed upon MM infiltration. Although CD16(+) mature
      myeloid cells constituted about half of the APRIL-producing cells in healthy BM,
      CD16(-) Elastase(+) myeloid precursor cells were predominant in MM-infiltrated
      BM. Myeloid precursor cells secreted all the APRIL they produced, and binding of
      secreted APRIL to MM cells, strictly dependent of heparan sulfate carried by
      CD138, resulted in an in situ internalization by tumor cells. This indicated
      APRIL consumption by MM in BM. Taken together, our data show that myelopoiesis
      dysregulation characterized by an increased proportion of precursor cells occurs
      in MM patients. Such dysregulation correlates with a stable expression of the MM
      promoting factor APRIL in infiltrated BM. 

PMID- 25753926
TI  - The flow cytometry-defined light chain cytoplasmic immunoglobulin index and an
      associated 12-gene expression signature are independent prognostic factors in
      multiple myeloma.
AB  - As part of Total Therapy (TT) 3b, baseline marrow aspirates were subjected to two
      color flow cytometry of nuclear DNA content and cytoplasmic immunoglobulin
      (DNA/CIG) as well as plasma cell gene expression profiling (GEP). DNA/CIG-derived
      parameters, GEP and standard clinical variables were examined for their effects
      on overall survival (OS) and progression-free survival (PFS). Among DNA/CIG
      parameters, the percentage of the light chain-restricted (LCR) cells and their
      cytoplasmic immunoglobulin index (CIg) were linked to poor outcome. In the
      absence of GEP data, low CIg <2.8, albumin <3.5 g/dl and age ?65 years were
      significantly associated with inferior OS and PFS. When GEP information was
      included, low CIg survived the model along with GEP70-defined high risk and low
      albumin. Low CIg was linked to beta-2-microglobulin >5.5 mg/l, a percentage of
      LCR cells exceeding 50%, C-reactive protein ?8 mg/l and GEP-derived high
      centrosome index. Further analysis revealed an association of low CIg with 12
      gene probes implicated in cell cycle regulation, differentiation and drug
      transportation from which a risk score was developed in TT3b that held prognostic
      significance also in TT3a, TT2 and HOVON trials, thus validating its general
      applicability. Low CIg is a powerful new prognostic variable and has identified
      potentially drug-able targets. 

PMID- 25753927
TI  - New simple prognostic score for primary biliary cirrhosis: Albumin-bilirubin
      score.
AB  - BACKGROUND AND AIM: Serum albumin and bilirubin are the most significant
      independent prognostic factors to predict hepatic events in patients with primary
      biliary cirrhosis (PBC). We aimed to investigate the prognostic significance of a
      new prognostic score, the albumin-bilirubin (ALBI) score, among PBC patients.
      METHODS: In a retrospective longitudinal cohort of 61 Chinese PBC patients with
      follow-up period up to 18.3 years, the prognostic performance of the ALBI in
      prediction of hepatic events was compared with other well-established prognostic
      scores: Child-Pugh score, model of end-stage liver disease, Mayo risk score,
      Yale, European, and Newcastle models. RESULTS: Fifteen patients (24.6%) developed
      hepatic events during follow-up. The c-index (0.894) and chi(2) by likelihood
      ratio test (36.34) of the ALBI score were highest in comparison to other models.
      The ALBI score was the only independent prognostic factor by multivariate
      analysis and its adjusted hazard ratio of developing hepatic event was 27.8 (P <
      0.001). There were three prognostically different groups stratified by the ALBI
      score: ALBI grade 1 (<= -2.60), grade 2 (> -2.60 to -1.39), and grade 3 (> -1.39)
      groups. The 2-, 5-, and 10-year event-free survivals for grade 1, grade 2, and
      grade 3 groups were 100.0% versus 100.0% versus 57.1%, 100.0% versus 88.5% versus
      14.3%, and 100.0% versus 81.7% versus 0.0%, respectively (P < 0.001). CONCLUSION:
      The ALBI score is readily derived from a blood test without using those factors
      evaluated subjectively or obtained by invasive procedures. It is an independent
      prognostic factor for PBC patients and provides better/similar prognostic
      performance compared with other prognostic scores.

PMID- 25753928
TI  - Oral health-related quality of life among an Australian sample of people who
      inject drugs.
AB  - OBJECTIVES: People who inject drugs (PWID) have poor oral health. However, their
      oral health-related quality of life (OHRQoL) is unknown. Our study was designed
      to measure the OHRQoL of PWID. METHODS: The Oral Health Impact Profile-14 (OHIP
      14) was administered to 794 PWID recruited in Australian capital cities as part
      of the 2013 Illicit Drug Reporting System (IDRS). Three OHIP-14 summary
      indicators were examined: "Prevalence" (proportion reporting >=1 item at least
      "fairly often"), "severity" (mean total OHIP-14 score), and "extent" (number of
      impacts reported at least "fairly often"). Associations between "prevalence" and
      "extent" and variables drawn from the health, drug use, and social domains were
      investigated. RESULTS: All OHIP-14 summary indicators among IDRS participants
      were significantly higher than in the general Australian population. In
      multivariate analysis, the "prevalence" indicator was significantly and
      positively associated with female gender [adjusted odds ratio (AOR) = 1.75, 95%
      CI 1.27-2.38], those born in Australia (AOR = 2, 95% CI 1.25-3.23), not
      completing Year 10 compared with those who had completed Year 12 or a higher
      qualification (AOR = 1.59, 95% CI 1.03-2.44), and methadone treatment (AOR =
      1.61, 95% CI 1.14-2.29). The "extent" indicator was significantly and positively
      associated with female gender [adjusted incidence rate ratio (AIRR) = 1.56, 95%
      CI 1.19-2.08], unemployment (AIRR = 1.59, 95% CI 1.01-2.44), and having an
      injecting career of 10-20 years (AIRR = 1.76, 95% CI 1.03-3.01). CONCLUSIONS:
      PWID have poorer OHRQoL than the Australian general population. Poor OHRQoL was
      particularly common in female PWID and those with longer injecting careers.
      Interventions to improve the oral health of PWID may improve their OHRQoL.

PMID- 25753929
TI  - Neutral particle mass spectrometry with nanomechanical systems.
AB  - Current approaches to mass spectrometry (MS) require ionization of the analytes
      of interest. For high-mass species, the resulting charge state distribution can
      be complex and difficult to interpret correctly. Here, using a setup comprising
      both conventional time-of-flight MS (TOF-MS) and nano-electromechanical systems
      based MS (NEMS-MS) in situ, we show directly that NEMS-MS analysis is insensitive
      to charge state: the spectrum consists of a single peak whatever the species'
      charge state, making it significantly clearer than existing MS analysis. In
      subsequent tests, all the charged particles are electrostatically removed from
      the beam, and unlike TOF-MS, NEMS-MS can still measure masses. This demonstrates
      the possibility to measure mass spectra for neutral particles. Thus, it is
      possible to envisage MS-based studies of analytes that are incompatible with
      current ionization techniques and the way is now open for the development of
      cutting-edge system architectures with unique analytical capability. 

PMID- 25753930
TI  - Alcohol abstinence or harm-reduction? Parental messages for college-bound light
      drinkers.
AB  - Parental communications about alcohol can have a significant impact on college
      students' alcohol use; however, it is unclear what types of communication may be
      most beneficial for reducing alcohol risk, particularly among students who have
      already initiated alcohol use. The present research examines differences in
      alcohol use and employment of drinking protective behavioral strategies between
      pre-college matriculation high school seniors receiving predominantly abstinence
      parent messaging and students primarily receiving harm-reduction parent
      messaging. Students who identified as light drinkers were recruited during their
      last month in high school and completed an online assessment of alcohol use and
      parent alcohol communication. Analyses revealed that, in comparison to light
      drinkers who primarily received harm-reduction messaging from parents, light
      drinkers who received more abstinence messaging reported less frequent alcohol
      use, lower peak alcohol consumption, and greater use of protective drinking
      strategies aimed at changing the way they drank and avoiding serious hazards
      associated with drinking. Findings from this study underscore the utility of
      messages related to abstinence even for parents who are aware that their children
      have had previous experiences with alcohol and highlight the need for
      longitudinal research assessing additional mechanisms associated with message
      efficacy among light, moderate and heavy drinking students transitioning to
      college. 

PMID- 25753931
TI  - Structural stigma and sexual orientation disparities in adolescent drug use.
AB  - Although epidemiologic studies have established the existence of large sexual
      orientation disparities in illicit drug use among adolescents and young adults,
      the determinants of these disparities remain understudied. This study sought to
      determine whether sexual orientation disparities in illicit drug use are
      potentiated in states that are characterized by high levels of stigma surrounding
      sexual minorities. State-level structural stigma was coded using a previously
      established measure based on a 4-item composite index: (1) density of same-sex
      couples; (2) proportion of Gay-Straight Alliances per public high school; (3) 5
      policies related to sexual orientation discrimination (e.g., same-sex marriage,
      employment non-discrimination); and (4) public opinion toward homosexuality
      (aggregated responses from 41 national polls). The index was linked to individual
      level data from the Growing Up Today Study, a prospective community-based study
      of adolescents (2001-2010). Sexual minorities report greater illicit drug use
      than their heterosexual peers. However, for both men and women, there were
      statistically significant interactions between sexual orientation status and
      structural stigma, such that sexual orientation disparities in marijuana and
      illicit drug use were more pronounced in high-structural stigma states than in
      low-structural stigma states, controlling for individual- and state-level
      confounders. For instance, among men, the risk ratio indicating the association
      between sexual orientation and marijuana use was 24% greater in high- versus low
      structural stigma states, and for women it was 28% greater in high- versus low
      structural stigma states. Stigma in the form of social policies and attitudes may
      contribute to sexual orientation disparities in illicit drug use. 

PMID- 25753932
TI  - CBT for high anxiety sensitivity: alcohol outcomes.
AB  - INTRODUCTION: High anxiety sensitivity (AS) has been associated with greater
      alcohol consumption and alcohol-related problems as well as greater sensitivity
      to the anxiety-reducing effects of alcohol and greater risky negative
      reinforcement motives for drinking. The present study reported on the alcohol
      related outcomes of a telephone-delivered cognitive behavioral treatment (CBT)
      designed to reduce high AS. METHODS: Eighty individuals with high AS (M age=36
      years; 79% women; 76% Caucasian) seeking treatment for their AS-related concerns
      participated in the study and were randomly assigned to an eight week telephone
      CBT program or a waiting list control. Participants completed measures of
      drinking motives and problem drinking at pre- and post-treatment. RESULTS:
      Multilevel modeling showed that the treatment was successful in reducing AS. The
      treatment also resulted in specific reductions in drinking to cope with anxiety
      motives as well as physical alcohol-related problems. Mediated moderation
      analyses showed treatment-related changes in AS mediated changes in drinking to
      cope with anxiety motives. Changes in drinking to cope with anxiety motives
      mediated changes in physical alcohol-related problems. CONCLUSIONS: Results of
      the present study suggest that an AS-targeted intervention may have implications
      for reducing risky alcohol use cognitions and behaviors. Further research is
      needed in a sample of problem drinkers.

PMID- 25753933
TI  - Women and HIV: the urgent need for more research and policy attention in the
      Middle East and North Africa region.

PMID- 25753934
TI  - Is seborrhoeic dermatitis associated with a diffuse, low-grade folliculitis and
      progressive cicatricial alopecia?
AB  - An association between adult scalp seborrhoeic dermatitis and cicatricial hair
      loss has not previously been convincingly established. This study seeks to
      demonstrate a unique relationship between a clinically identifiable chronic scalp
      dermatitis-folliculitis with the characteristic histological features of low
      grade inflammatory fibrosing alopecia, resulting in a distinctive progressive
      cicatricial alopecia which we believe is prevalent and hitherto unrecognised, and
      befits the description of seborrhoeic folliculitis. The clinical, epidemiological
      and histopathological features of seborrhoeic folliculitis are demonstrated to
      establish its unique status among the disorders of adult diffuse cicatricial
      alopecia. 

PMID- 25753935
TI  - Multimorbidity in risk stratification tools to predict negative outcomes in adult
      population.
AB  - INTRODUCTION: Risk stratification tools were developed to assess risk of negative
      health outcomes. These tools assess a variety of variables and clinical factors
      and they can be used to identify targets of potential interventions and to
      develop care plans. The role of multimorbidity in these tools has never been
      assessed. OBJECTIVES: To summarize validated risk stratification tools for
      predicting negative outcomes, with a specific focus on multimorbidity. METHODS:
      MEDLINE, Cochrane Central Register of Controlled Trials and PubMed database were
      interrogated for studies concerning risk prediction models in medical
      populations. Review was conducted to identify prediction models tested with
      patients in both derivation and validation cohorts. A qualitative synthesis was
      performed focusing particularly on how multimorbidity is assessed by each
      algorithm and how much this weighs in the ability of discrimination. RESULTS: Of
      3674 citations reviewed, 36 articles met criteria. Of these, 29 had as outcome
      hospital admission/readmission. The most common multimorbidity measure employed
      in the models was the Charlson Comorbidity Index (12 articles). C-statistics
      ranged between 0.5 and 0.85 in predicting hospital admission/ readmission. The
      highest c-statistics was 0.83 in models with disability as outcome. For
      healthcare cost, models which used ACG-PM case mix explained better the
      variability of total costs. CONCLUSIONS: This review suggests that predictive
      risk models which employ multimorbidity as predictor variable are more accurate;
      CHF, cerebro-vascular disease, COPD and diabetes were strong predictors in some
      of the reviewed models. However, the variability in the risk factors used in
      these models does not allow making assumptions.

PMID- 25753936
TI  - Association between polymorphism within the RYR2 receptor and development of
      statin-associated myalgia/myopathy in the Czech population.

PMID- 25753938
TI  - Variant CJD and blood transfusion.

PMID- 25753937
TI  - Rheumatoid arthritis affects left ventricular mass: Systematic review and meta
      analysis.
AB  - BACKGROUND: Cardiovascular disease represents one of the most important extra
      articular causes of morbidity and mortality in patients with rheumatoid arthritis
      (RA). Evidences showed that several cardiac structures can be affected during the
      course of the disease as well as abnormalities of left ventricular diastolic
      filling. Contrasting data are available about left ventricular mass (LVM)
      involvement in patients asymptomatic for cardiovascular disease. The purpose of
      this systematic review and meta-analysis is to summarize the effects of RA on LVM
      in rheumatoid arthritis patients without cardiovascular disease. METHODS: A
      systematic research of the current case-control studies was conducted in Medline
      on November 20th, 2013. Studies were included if data of measurements of LVM were
      reported. The pooled mean effect size estimate was calculated according to
      methods described by Hedges and Olkin. RESULTS: Sixteen eligible studies were
      included in this meta-analysis. RA determines an increase of absolute and indexed
      LVM compared with control patients [standardized mean difference (95% CI):
      0.41(0.15-0.66) and 0.47(0.32-0.62), respectively]. On the contrary, posterior
      wall thickness did not show a significant RA effect. Finally, a significant
      positive effect of RA on interventricular wall thickness was found [standardized
      mean difference (95% CI): 0.39 (0.07-0.71)]. CONCLUSIONS: Results of this meta
      analysis suggest that increased absolute and indexed LVM seem to be
      characteristic of RA patients with a fundamental clinical significance since they
      are related to an increased risk of cardiovascular morbidity and mortality. Our
      data suggest the use of LVM as surrogate end-point for clinical trials involving
      RA patients.

PMID- 25753939
TI  - Functional polymorphisms in the promoter region of MMP-2 and MMP-9 and
      susceptibility to obstructive sleep apnea.
AB  - Genetic susceptibility to obstructive sleep apnea (OSA) has been a research focus
      in the scientific community in the past few years. In this study, we recruited
      375 subjects to investigate whether functional polymorphisms in the promoter
      region of matrix metalloproteinase (MMP)-2 (-1306C/T) and MMP-9 (-1562C/T)
      increased susceptibility to OSA. Our study showed no significant association
      between MMP-2 -1306C/T polymorphism and risk of OSA (T vs. C: OR = 1.01, 95% CI =
      0.67-1.52; P = 0.97). Compared with the MMP-9 -1562C allele, the -1562T allele
      was associated with increased risk of OSA (T vs. C: OR = 1.56, 95% CI = 1.02
      2.39; P = 0.04). However, neither MMP-2 -1306C/T nor MMP-9 -1562C/T polymorphism
      was found to be associated with severity of the disease. Our study suggested that
      the MMP-2 -1306C/T polymorphism was not associated with OSA susceptibility,
      whereas the MMP-9 -1562T allele was associated with increased risk of OSA. 

PMID- 25753940
TI  - 5' and 3' beta-globin haplotypes in purepechas and Tarahumaras, two Mexican
      indigenous groups.
AB  - OBJECTIVE: The purpose of this study was to determine the beta-globin cluster
      haplotype variability of two Mexican indigenous groups-Purepechas (PUR) and
      Tarahumaras (TAR)-and their relationship with other world populations. METHODS:
      The 5' and 3' haplotypes (Hp) of the beta globin cluster in 71 PUR and 53 TAR
      individuals were analyzed. Five polymorphisms in the 5'Hp (epsilon, (G) gamma,
      (A) gamma, 5'psibeta and 3'psibeta) and five in the 3'Hp (IVS2: 16, 46, 74, 81
      and 3' end +339) were identified by restriction enzymes and direct DNA
      sequencing. 5'Hp and 3'Hp frequencies in PUR and TAR were compared with reported
      frequencies from 47 and 10 worldwide populations, respectively. RESULTS: Sixteen
      different 5'Hps were observed in the indigenous Mexican groups, 11 in each
      population, with the most common being 5'Hp 1. Eight 3'Hps were detected, seven
      in PUR and six in TAR, the most frequent being 3'Hp C. Three new 3'Hps were
      found, A8 (CTGCT) in both populations, C9 (GTGCA) in TAR and E1 (GTTCT) in PUR.
      The comparative analysis showed that 5'Hp frequencies in PUR were significantly
      different than those in all populations except the Brazilian-Guarani, while TAR
      were significantly similar to Ache and North Han Chinese. 3'Hp frequencies were
      similar between PUR and TAR, as well as with Nuu-Chah-Nulth, Mongolian and
      Sumatran populations. CONCLUSIONS: The 5'Hp analysis showed great variability in
      worldwide populations, including PUR and TAR, while 3'Hp frequencies were similar
      among indigenous Mexican and other populations with Asiatic origins. This
      suggests that 5'Hp exposes the microevolutionary process of each population and
      the 3'Hp establishes genetic relationships among populations.

PMID- 25753941
TI  - Rh(III)-catalyzed oxime ether-directed heteroarylation of arene through oxidative
      C-H/C-H cross-coupling.
AB  - A rhodium(III)-catalyzed dehydrogenative cross-coupling reaction has been
      developed for the synthesis of bi(hetero)aryl structures by using oxime ethers as
      the directing group. This protocol features a relatively broad substrate scope
      and a good tolerance of functional groups.

PMID- 25753942
TI  - Considerations on mental disorders: a neurophysiological approach.

PMID- 25753943
TI  - Association of vitamin D3 with alveolar bone regeneration in dogs.
AB  - Designed sockets prepared on the mandibles of nine Beagle dogs were divided into
      three groups: Calcitriol +Alloplast, Alloplast and Empty. Five of the nine dogs
      received Vit.D3 and calcium supplement (Vit.D/Ca group), while the other four
      dogs without supplements were assigned to Non-Vit.D/Ca group. After 4 weeks, the
      extent of vertical ridge resorption (VRR), bone density (density), new bone
      formation (NBF) and implant stability quotient (ISQ) were measured. Following
      systemic Vit.D/Ca administration, the Empty subgroup showed significant
      differences from the Calcitriol + Alloplast subgroup on variants NBF/Density/VRR
      and the Alloplast subgroup on items NBF/Density/ISQ/VRR. Alternatively, the
      Calcitriol + Alloplast subgroup revealed higher values of NBF/Density/ISQ (P <
      0.001) and a lower VRR value (P = 0.001) than the Alloplast subgroup. Although
      there were no significant differences in NBF (P = 0.349), density (P = 0.796),
      ISQ (P = 0.577) and VRR (0.979) comparisons on alloplast treatment between the
      Vit.D/Ca and Non-Vit.D/Ca groups, local application with Calcitriol + Alloplast
      demonstrated better NBF/Density/ISQ (P = 0.02 to <0.001) effects than which of
      Alloplast subgroups. Consequently, the results showed that both systemic and
      local vitamin D3 treatment might accelerate bone regeneration in dogs. Within the
      using dose, systemic vitamin D3 treatment displayed a superior stimulating effect
      than local vitamin D3 application did. 

PMID- 25753944
TI  - The median preoptic nucleus: front and centre for the regulation of body fluid,
      sodium, temperature, sleep and cardiovascular homeostasis.
AB  - Located in the midline anterior wall of the third cerebral ventricle (i.e. the
      lamina terminalis), the median preoptic nucleus (MnPO) receives a unique set of
      afferent neural inputs from fore-, mid- and hindbrain. These afferent connections
      enable it to receive neural signals related to several important aspects of
      homeostasis. Included in these afferent projections are (i) neural inputs from
      two adjacent circumventricular organs, the subfornical organ and organum
      vasculosum laminae terminalis, that respond to hypertonicity, circulating
      angiotensin II or other humoural factors, (ii) signals from cutaneous warm and
      cold receptors that are relayed to MnPO, respectively, via different subnuclei in
      the lateral parabrachial nucleus and (iii) input from the medulla associated with
      baroreceptor and vagal afferents. These afferent signals reach appropriate
      neurones within the MnPO that enable relevant neural outputs, both excitatory and
      inhibitory, to be activated or inhibited. The efferent neural pathways that
      proceed from the MnPO terminate on (i) neuroendocrine cells in the hypothalamic
      supraoptic and paraventricular nuclei to regulate vasopressin release, while
      polysynaptic pathways from MnPO to cortical sites may drive thirst and water
      intake, (ii) thermoregulatory pathways to the dorsomedial hypothalamic nucleus
      and medullary raphe to regulate shivering, brown adipose tissue and skin
      vasoconstriction, (iii) parvocellular neurones in the hypothalamic
      paraventricular nucleus that drive autonomic pathways influencing cardiovascular
      function. As well, (iv) other efferent pathways from the MnPO to sites in the
      ventrolateral pre-optic nucleus, perifornical region of the lateral hypothalamic
      area and midbrain influence sleep mechanisms.

PMID- 25753945
TI  - Wounding of Arabidopsis halleri leaves enhances cadmium accumulation that acts as
      a defense against herbivory.
AB  - Approximately 0.2% of all angiosperms are classified as metal hyperaccumulators
      based on their extraordinarily high leaf metal contents, for example >1% zinc,
      >0.1% nickel or >0.01% cadmium (Cd) in dry biomass. So far, metal
      hyperaccumulation has been considered to be a taxon-wide, constitutively
      expressed trait, the extent of which depends solely on available metal
      concentrations in the soil. Here we show that in the facultative metallophyte
      Arabidopsis halleri, both insect herbivory and mechanical wounding of leaves
      trigger an increase specifically in leaf Cd accumulation. Moreover, the Cd
      concentrations accumulated in leaves can serve as an elemental defense against
      herbivory by larvae of the Brassicaceae specialist small white (Pieris rapae),
      thus allowing the plant to take advantage of this non-essential trace element and
      toxin. Metal homeostasis genes are overrepresented in the systemic
      transcriptional response of roots to the wounding of leaves in A. halleri,
      supporting that leaf Cd accumulation is preceded by systemic signaling events. A
      similar, but quantitatively less pronounced transcriptional response was observed
      in A. thaliana, suggesting that the systemically regulated modulation of metal
      homeostasis in response to leaf wounding also occurs in non-hyperaccumulator
      plants. This is the first report of an environmental stimulus influencing metal
      hyperaccumulation.

PMID- 25753946
TI  - Shotgun metabolomic approach based on mass spectrometry for hepatic mitochondria
      of mice under arsenic exposure.
AB  - Mass spectrometry (MS)-based toxicometabolomics requires analytical approaches
      for obtaining unbiased metabolic profiles. The present work explores the general
      application of direct infusion MS using a high mass resolution analyzer (a hybrid
      systems triple quadrupole-time-of-flight) and a complementary gas chromatography
      MS analysis to mitochondria extracts from mouse hepatic cells, emphasizing on
      mitochondria isolation from hepatic cells with a commercial kit, sample treatment
      after cell lysis, comprehensive metabolomic analysis and pattern recognition from
      metabolic profiles. Finally, the metabolomic platform was successfully checked on
      a case-study based on the exposure experiment of mice Mus musculus to inorganic
      arsenic during 12 days. Endogenous metabolites alterations were recognized by
      partial least squares-discriminant analysis. Subsequently, metabolites were
      identified by combining MS/MS analysis and metabolomics databases. This work
      reports for the first time the effects of As-exposure on hepatic mitochondria
      metabolic pathways based on MS, and reveals disturbances in Krebs cycle, beta
      oxidation pathway, amino acids degradation and perturbations in creatine levels.
      This non-target analysis provides extensive metabolic information from
      mitochondrial organelle, which could be applied to toxicology, pharmacology and
      clinical studies.

PMID- 25753947
TI  - Single-Cell XIST Expression in Human Preimplantation Embryos and Newly
      Reprogrammed Female Induced Pluripotent Stem Cells.
AB  - The process of X chromosome inactivation (XCI) during reprogramming to produce
      human induced pluripotent stem cells (iPSCs), as well as during the extensive
      programming that occurs in human preimplantation development, is not well
      understood. Indeed, studies of XCI during reprogramming to iPSCs report cells
      with two active X chromosomes and/or cells with one inactive X chromosome. Here,
      we examine expression of the long noncoding RNA, XIST, in single cells of human
      embryos through the oocyte-to-embryo transition and in new mRNA reprogrammed
      iPSCs. We show that XIST is first expressed beginning at the 4-cell stage,
      coincident with the onset of embryonic genome activation in an asynchronous
      manner. Additionally, we report that mRNA reprogramming produces iPSCs that
      initially express XIST transcript; however, expression is rapidly lost with
      culture. Loss of XIST and H3K27me3 enrichment at the inactive X chromosome at
      late passage results in X chromosome expression changes. Our data may contribute
      to applications in disease modeling and potential translational applications of
      female stem cells.

PMID- 25753949
TI  - Uthrene, a radically new molecule?
AB  - We have studied uthrene with a large range of quantum chemical models. Uthrene is
      predicted to be naturally twisted and to possess a triplet ground state, making
      it the smallest non-planar polycyclic biradical that can be derived from
      graphene. 

PMID- 25753948
TI  - Motivational processes and well-being in cardiac rehabilitation: a self
      determination theory perspective.
AB  - This research examined the processes underpinning changes in psychological well
      being and behavioural regulation in cardiac rehabilitation (CR) patients using
      self-determination theory (SDT). A repeated measures design was used to identify
      the longitudinal relationships between SDT variables, psychological well-being
      and exercise behaviour during and following a structured CR programme.
      Participants were 389 cardiac patients (aged 36-84 years; M(age) = 64 +/- 9
      years; 34.3% female) referred to a 12-week-supervised CR programme. Psychological
      need satisfaction, behavioural regulation, health-related quality of life,
      physical self-worth, anxiety and depression were measured at programme entry,
      exit and six month post-programme. During the programme, increases in autonomy
      satisfaction predicted positive changes in behavioural regulation, and
      improvements in competence and relatedness satisfaction predicted improvements in
      behavioural regulation and well-being. Competence satisfaction also positively
      predicted habitual physical activity. Decreases in external regulation and
      increases in intrinsic motivation predicted improvements in physical self-worth
      and physical well-being, respectively. Significant longitudinal relationships
      were identified whereby changes during the programme predicted changes in
      habitual physical activity and the mental quality of life from exit to six month
      follow-up. Findings provide insight into the factors explaining psychological
      changes seen during CR. They highlight the importance of increasing patients'
      perceptions of psychological need satisfaction and self-determined motivation to
      improve well-being during the structured component of a CR programme and longer
      term physical activity.

PMID- 25753950
TI  - Combining reverse genetics and nuclear magnetic resonance-based metabolomics
      unravels trypanosome-specific metabolic pathways.
AB  - Numerous eukaryotes have developed specific metabolic traits that are not present
      in extensively studied model organisms. For instance, the procyclic insect form
      of Trypanosoma brucei, a parasite responsible for sleeping sickness in its
      mammalian-specific bloodstream form, metabolizes glucose into excreted succinate
      and acetate through pathways with unique features. Succinate is primarily
      produced from glucose-derived phosphoenolpyruvate in peroxisome-like organelles,
      also known as glycosomes, by a soluble NADH-dependent fumarate reductase only
      described in trypanosomes so far. Acetate is produced in the mitochondrion of the
      parasite from acetyl-CoA by a CoA-transferase, which forms an ATP-producing cycle
      with succinyl-CoA synthetase. The role of this cycle in ATP production was
      recently demonstrated in procyclic trypanosomes and has only been proposed so far
      for anaerobic organisms, in addition to trypanosomatids. We review how nuclear
      magnetic resonance spectrometry can be used to analyze the metabolic network
      perturbed by deletion (knockout) or downregulation (RNAi) of the candidate genes
      involved in these two particular metabolic pathways of procyclic trypanosomes.
      The role of succinate and acetate production in trypanosomes is discussed, as
      well as the connections between the succinate and acetate branches, which
      increase the metabolic flexibility probably required by the parasite to deal with
      environmental changes such as oxidative stress. 

PMID- 25753951
TI  - Usability and Workload of Access Technology for People With Severe Motor
      Impairment: A Comparison of Brain-Computer Interfacing and Eye Tracking.
AB  - BACKGROUND: Eye trackers are widely used among people with amyotrophic lateral
      sclerosis, and their benefits to quality of life have been previously shown. On
      the contrary, Brain-computer interfaces (BCIs) are still quite a novel
      technology, which also serves as an access technology for people with severe
      motor impairment. OBJECTIVE: To compare a visual P300-based BCI and an eye
      tracker in terms of information transfer rate (ITR), usability, and cognitive
      workload in users with motor impairments. METHODS: Each participant performed 3
      spelling tasks, over 4 total sessions, using an Internet browser, which was
      controlled by a spelling interface that was suitable for use with either the BCI
      or the eye tracker. At the end of each session, participants evaluated usability
      and cognitive workload of the system. RESULTS: ITR and System Usability Scale
      (SUS) score were higher for the eye tracker (Wilcoxon signed-rank test: ITR T =
      9, P = .016; SUS T = 12.50, P = .035). Cognitive workload was higher for the BCI
      (T = 4; P = .003). CONCLUSIONS: Although BCIs could be potentially useful for
      people with severe physical disabilities, we showed that the usability of BCIs
      based on the visual P300 remains inferior to eye tracking. We suggest that future
      research on visual BCIs should use eye tracking-based control as a comparison to
      evaluate performance or focus on nonvisual paradigms for persons who have lost
      gaze control.

PMID- 25753952
TI  - Effect of monovalent rotavirus vaccine on rotavirus disease burden and
      circulating rotavirus strains among children in Morocco.
AB  - Rotarix(TM) vaccine was introduced into the National Program of Immunization of
      Morocco in October 2010, reaching quickly 87% of the target population of
      children nationally. The incidence of rotavirus gastroenteritis and the
      prevalence of circulating rotavirus strains has been monitored in three sentinel
      hospitals since June 2006. The average percentage of rotavirus positive cases
      among all children under 5 years old hospitalized for gastroenteritis during the
      pre-vaccine period (2006-2010) was 44%. This percentage dropped to 29%, 15% and
      24% in the 3 years post vaccine introduction (2011, 2012 and 2013), which is a
      decline of 34%, 66%, and 45%, respectively. Declines in prevalence were greatest
      among children 0-1 years of age (53%) and were most prominent during the winter
      and autumn rotavirus season. The prevalence of the G2P[4] and G9P[8] genotype
      sharply increased in the post vaccine period (2011-2013) compared to the previous
      seasons (2006-2010). Rotavirus vaccines have reduced greatly the number of
      children hospitalized due to rotavirus infection at the three sentinel hospitals;
      it is however unclear if the predominance of G2P[4] and G9P[8] genotypes is
      related to the vaccine introduction, or if this is attributable to normal
      genotype fluctuations. Continued surveillance will be pivotal to answer this
      question in the future.

PMID- 25753953
TI  - Macrodiolide formation by the thioesterase of a modular polyketide synthase.
AB  - Elaiophylin is an unusual C2 -symmetric antibiotic macrodiolide produced on a
      bacterial modular polyketide synthase assembly line. To probe the mechanism and
      selectivity of diolide formation, we sought to reconstitute ring formation in
      vitro by using a non-natural substrate. Incubation of recombinant elaiophylin
      thioesterase/cyclase with a synthetic pentaketide analogue of the presumed
      monomeric polyketide precursor of elaiophylin, specifically its N
      acetylcysteamine thioester, produced a novel 16-membered C2 -symmetric
      macrodiolide. A linear dimeric thioester is an intermediate in ring formation,
      which indicates iterative use of the thioesterase active site in ligation and
      subsequent cyclization. Furthermore, the elaiophylin thioesterase acts on a
      mixture of pentaketide and tetraketide thioesters to give both the symmetric
      decaketide diolide and the novel asymmetric hybrid nonaketide diolide. Such
      thioesterases have potential as tools for the in vitro construction of novel
      diolides. 

PMID- 25753954
TI  - Prediction model for 3-year rupture risk of unruptured cerebral aneurysms in
      Japanese patients.
AB  - OBJECTIVE: To build a prediction model that estimates the 3-year rupture risk of
      unruptured saccular cerebral aneurysms. METHODS: Survival analysis was done using
      each aneurysm as the unit for analysis. Derivation data were from the Unruptured
      Cerebral Aneurysm Study (UCAS) in Japan. It consists of patients with unruptured
      cerebral aneurysms enrolled between 2000 and 2004 at neurosurgical departments at
      tertiary care hospitals in Japan. The model was presented as a scoring system,
      and aneurysms were classified into 4 risk grades by predicted 3-year rupture
      risk: I, < 1%; II, 1 to 3%; III, 3 to 9%, and IV, >9%. The discrimination
      property and calibration plot of the model were evaluated with external
      validation data. They were a combination of 3 Japanese cohort studies: UCAS II,
      the Small Unruptured Intracranial Aneurysm Verification study, and the study at
      Jikei University School of Medicine. RESULTS: The derivation data include 6,606
      unruptured cerebral aneurysms in 5,651 patients. During the 11,482 aneurysm-year
      follow-up period, 107 ruptures were observed. The predictors chosen for the
      scoring system were patient age, sex, and hypertension, along with aneurysm size,
      location, and the presence of a daughter sac. The 3-year risk of rupture ranged
      from <1% to >15% depending on the individual characteristics of patients and
      aneurysms. External validation indicated good discrimination and calibration
      properties. INTERPRETATION: A simple scoring system that only needs easily
      available patient and aneurysmal information was constructed. This can be used in
      clinical decision making regarding management of unruptured cerebral aneurysms.

PMID- 25753956
TI  - The yin-yang sign.

PMID- 25753955
TI  - Radiogenomics of clear cell renal cell carcinoma: preliminary findings of The
      Cancer Genome Atlas-Renal Cell Carcinoma (TCGA-RCC) Imaging Research Group.
AB  - PURPOSE: To investigate associations between imaging features and mutational
      status of clear cell renal cell carcinoma (ccRCC). MATERIALS AND METHODS: This
      multi-institutional, multi-reader study included 103 patients (77 men; median age
      59 years, range 34-79) with ccRCC examined with CT in 81 patients, MRI in 19, and
      both CT and MRI in three; images were downloaded from The Cancer Imaging Archive,
      an NCI-funded project for genome-mapping and analyses. Imaging features [size
      (mm), margin (well-defined or ill-defined), composition (solid or cystic),
      necrosis (for solid tumors: 0%, 1%-33%, 34%-66% or >66%), growth pattern
      (endophytic, <50% exophytic, or >=50% exophytic), and calcification (present,
      absent, or indeterminate)] were reviewed independently by three readers blinded
      to mutational data. The association of imaging features with mutational status
      (VHL, BAP1, PBRM1, SETD2, KDM5C, and MUC4) was assessed. RESULTS: Median tumor
      size was 49 mm (range 14-162 mm), 73 (71%) tumors had well-defined margins, 98
      (95%) tumors were solid, 95 (92%) showed presence of necrosis, 46 (45%) had >=50%
      exophytic component, and 18 (19.8%) had calcification. VHL (n = 52) and PBRM1 (n
      = 24) were the most common mutations. BAP1 mutation was associated with ill
      defined margin and presence of calcification (p = 0.02 and 0.002, respectively,
      Pearson's chi (2) test); MUC4 mutation was associated with an exophytic growth
      pattern (p = 0.002, Mann-Whitney U test). CONCLUSIONS: BAP1 mutation was
      associated with ill-defined tumor margins and presence of calcification; MUC4
      mutation was associated with exophytic growth. Given the known prognostic
      implications of BAP1 and MUC4 mutations, these results support using
      radiogenomics to aid in prognostication and management.

PMID- 25753957
TI  - Subknots in ideal knots, random knots, and knotted proteins.
AB  - We introduce disk matrices which encode the knotting of all subchains in circular
      knot configurations. The disk matrices allow us to dissect circular knots into
      their subknots, i.e. knot types formed by subchains of the global knot. The
      identification of subknots is based on the study of linear chains in which a knot
      type is associated to the chain by means of a spatially robust closure protocol.
      We characterize the sets of observed subknot types in global knots taking energy
      minimized shapes such as KnotPlot configurations and ideal geometric
      configurations. We compare the sets of observed subknots to knot types obtained
      by changing crossings in the classical prime knot diagrams. Building upon this
      analysis, we study the sets of subknots in random configurations of corresponding
      knot types. In many of the knot types we analyzed, the sets of subknots from the
      ideal geometric configurations are found in each of the hundreds of random
      configurations of the same global knot type. We also compare the sets of subknots
      observed in open protein knots with the subknots observed in the ideal
      configurations of the corresponding knot type. This comparison enables us to
      explain the specific dispositions of subknots in the analyzed protein knots. 

PMID- 25753958
TI  - A simplified spin and gradient echo approach for brain tumor perfusion imaging.
AB  - PURPOSE: In this study, we propose a simplified acquisition and analysis approach
      for spin and gradient echo (SAGE)-based dynamic susceptibility-contrast MRI (DSC
      MRI) data that is free of contrast agent T1 leakage effects. METHODS: A five-echo
      SAGE sequence was used to acquire DSC-MRI data in rat C6 tumors (n = 7).
      Nonlinear fitting of all echoes was performed to obtain T1-insensitive DeltaR2*
      and DeltaR2 time series. The simplified approach, which includes two gradient
      echoes and one spin echo, was also used to analytically compute T1-insensitive
      DeltaR2* using the two gradient echoes and DeltaR2 using all three echoes. The
      blood flow, blood volume, and vessel size values derived from each method were
      compared. RESULTS: In all cases, the five-echo and simplified SAGE DeltaR2* and
      DeltaR2 were in excellent agreement and demonstrated significant T1 leakage
      correction compared with the uncorrected single-echo data. The derived
      hemodynamic parameters for blood volume, blood flow, and vessel size were not
      significantly different between the two methods. CONCLUSIONS: The proposed
      simplified SAGE technique enables the acquisition of gradient and spin echo DSC
      MRI data corrected for T1 leakage effects yields parameters that are in agreement
      with the five-echo SAGE approach and does not require nonlinear fitting to
      extract DeltaR2* and DeltaR2 time series.

PMID- 25753959
TI  - [Drug management of agitation in emergency departments: The need of new
      assessments. Author's response to the letter on the article].

PMID- 25753960
TI  - [Nicotine replacement therapy for agitation in the emergency department. Letter
      on the article "Drug management of agitation in emergency departments:
      Theoretical recommendations and studies of practices"].

PMID- 25753961
TI  - [Which are the main causes of lower gastrointestinal bleedings in specialized
      proctology consultation?].

PMID- 25753962
TI  - [Methadone-induced edema: A case report].

PMID- 25753963
TI  - [Letter on the editorial: "Early diagnosis of Alzheimer's disease: Are we too
      close to the tree to see the forest?"].

PMID- 25753964
TI  - Immunoenzymatic and biochip array profiling of the biomarkers of inflammation and
      hemostatic activation processes in ESRD.
AB  - There is a high incidence of mortality due to cardiovascular events seen in
      patients with end-stage renal disease (ESRD) undergoing hemodialysis. Through
      utilization of biochip microarrays and enzyme-linked immunosorbent assay methods,
      we assessed various cardiac, inflammatory, thrombotic, and cerebral biomarkers to
      determine their roles in the hemostatic activation or inflammatory processes in
      ESRD. In this study, 72 patients on maintenance hemodialysis were recruited and
      53 normal healthy male and female adults volunteers. Blood samples from patients
      with ESRD were drawn prior to maintenance hemodialysis. Of the 15 statistically
      significant biomarkers, 10 were elevated in the ESRD group, most notably soluble
      tumor necrosis factor receptor 1, heart-type fatty acid binding protein, and von
      Willebrand factor activity. These results are consistent with previously reported
      studies proposing ESRD represents a poly-pathologic process with the activation
      of hemostatic and inflammatory processes, which contribute to the significant
      sequelae of cardiovascular disease seen in these patients. 

PMID- 25753965
TI  - Reduced Effect of Aspirin and Clopidogrel Following Hybrid Coronary
      Revascularization.
AB  - OBJECTIVE: Reduced effect of antiplatelet therapy following coronary artery
      bypass grafting is associated with reduced graft patency. We sought to evaluate
      the impact of hybrid coronary revascularization on the effect of aspirin and
      clopidogrel and whether high baseline platelet aggregation, high postoperative
      levels of platelet turnover, and acute-phase response may contribute to the
      effect. METHODS: We prospectively studied platelet aggregation (VerifyNow and
      Multiplate Analyzer), platelet turnover (immature platelets, mean platelet
      volume, and thrombopoietin), and acute-phase reactants (C-reactive protein, von
      Willebrand factor, and coagulation factor VIII) in 40 patients undergoing
      elective hybrid coronary revascularization (off-pump surgical revascularization
      through J-hemisternotomy followed by percutaneous coronary intervention [PCI]).
      Preoperative blood samples on- and off-aspirin were compared with blood samples
      obtained postoperatively, following PCI when dual antiplatelet therapy had been
      initiated and at 1-year follow-up. RESULTS: The antiplatelet effect of aspirin
      was significantly reduced in the early postoperative period as measured by
      VerifyNow Aspirin but not by Multiplate ASPI test. The antiplatelet effect of
      clopidogrel was significantly reduced following PCI as measured by VerifyNow
      P2Y12 and Multiplate ADP test. The level of baseline aggregation did not predict
      the antiplatelet effect of aspirin or clopidogrel, and no association was found
      between platelet aggregation and postoperative platelet turnover or acute-phase
      reaction. CONCLUSIONS: A transient reduction in the antiplatelet effect of
      aspirin and clopidogrel was observed after hybrid coronary revascularization
      despite limited surgical trauma and off-pump technique. Neither baseline platelet
      aggregation nor postoperatively increased platelet turnover and acute-phase
      response could explain this finding. ClinicalTrials.gov identifier, NCT02293928.

PMID- 25753966
TI  - Evaluation of VTE Prophylaxis in an Educational Hospital: Comparison Between the
      Institutional Guideline (Caprini 2006) and the ACCP Guideline (Ninth Edition).
AB  - Venous thromboembolism (VTE) is the most common preventable cause of hospital
      death; the burden of VTE includes the management of the acute event (deep vein
      thrombosis [DVT]/pulmonary embolism) and the chronic subsequents such as
      postthrombotic syndrome and recurrent DVT. All experts agree that despite the
      abundance of knowledge available on VTE and how to prevent it, it is still
      underused, and since the first step in prophylaxis is to identify those who are
      at high risk of VTE, several risk assessment models have been developed to
      identify these patients and provide appropriate prophylaxis. In our study, the
      institutional guideline in a tertiary educational hospital is the Caprini score
      (2006), a comparison was conducted between the institutional guideline and the
      American College of Chest Physicians guideline (ACCP ninth edition [ACCP-9]) in
      terms of the degree of agreement of the actual prophylaxis with the institutional
      guideline and the ACCP-9 and the differences in risk levels. The concordance with
      the ACCP-9 guideline was higher than with the institutional guideline,
      specifically in those patients receiving prophylaxis, and there was an
      overestimation of the risk levels in the institutional guideline, especially in
      medical patients. The replacement of the existing Caprini-2006 with the ACCP-9 is
      prudent, since it agrees with the physicians' clinical judgment and may result in
      reduced use of pharmacologic prophylaxis which could lead to lower costs and
      fewer adverse effects. 

PMID- 25753967
TI  - Synthesis of pyrido[2,1-b]quinazolin-11-ones and dipyrido[1,2-a:2',3'-d]pyrimidin
      5-ones by Pd/DIBPP-catalyzed dearomatizing carbonylation.
AB  - N-Fused heterocycles can be easily synthesized by palladium-catalyzed
      dearomatizing carbonylation using 1,3-bis(diisobutylphosphino)propane (DIBPP) as
      the ligand. Pyrido[2,1-b]quinazolin-11-ones were obtained from N-(2
      bromophenyl)pyridine-2-amines in up to quantitative yield and dipyrido[1,2
      a:2',3'-d]pyrimidin-5-ones from 3-bromo-N-(pyridine-2-yl)pyridine-2-amines in up
      to 84% yield. The cyclocarbonylation can be also realized without isolation of
      compound 1 and additional palladium catalyst. 

PMID- 25753968
TI  - Anticoagulation after catheter ablation of atrial fibrillation guided by
      implantable cardiac monitors.
AB  - BACKGROUND: Discontinuation of oral anticoagulation (OAC) after catheter ablation
      of atrial fibrillation (AF) is not recommended in patients with elevated CHADS2
      scores. However, a low incidence of thromboembolic events is reported when OAC is
      stopped in these patients. We introduce an algorithm for discontinuation of OAC
      after ablation based on the AF burden documented by implantable cardiac monitors
      (ICM). METHODS: Sixty-five patients with CHADS2 scores 1-3 free from AF 3 months
      after ablation (AF ablation [n = 49] or ablation of possible AF triggers [n =
      16]) were included. One day after implantation of the ICM, OAC was stopped.
      Patients performed a daily interrogation of the ICM which was programmed to alarm
      the patient if daily AF burden exceeded 1 hour. Study end point was the first
      recurrence of a daily AF burden >=1 hour or a thromboembolic event, which both
      triggered reinitiation of OAC. RESULTS: During a follow-up time of 32 +/- 12
      months (126 patient-years), 41 of the 65 patients (63%) had an AF burden <1 h/day
      and were able to stay off OAC. Twenty-one patients (32%) had to reinitiate OAC
      due to an AF burden >=1 hour and three patients due to other reasons. No stroke,
      transitory ischemic attack, or other thromboembolic event was observed during
      follow-up. CONCLUSIONS: Rhythm monitoring by ICM in patients who have stopped OAC
      after catheter ablation of AF or ablation of possible AF triggers seems to be a
      safe and promising method to monitor for AF recurrence. Within 1.3 years after
      ablation, about two-thirds of patients were able to stay off OAC.

PMID- 25753969
TI  - Investigation of a Possible Link Between Vaccination and the 2010 Sheep Pox
      Epizootic in Morocco.
AB  - Sheep pox is endemic in most parts of Northern Africa and has the potential to
      cause severe economic problems. Live attenuated vaccines are used in Morocco, and
      in many other countries, to control the disease. Sheep pox virus (SPPV) re
      appeared in 2010 causing a nodular clinical form previously not observed in
      Morocco. The severe clinical signs observed during the course of this outbreak
      and initial reports citing similarity in nucleotide sequence between the Moroccan
      vaccine strain and field isolates warranted a more in depth analysis of this
      epizootic. In this study, sequence analysis showed that isolates obtained from
      four provinces of eastern Morocco were identical, demonstrating that a single
      SPPV strain was responsible for the 2010 epizootic. In addition, the genome
      fragments sequenced and phylogenetic analyses undertaken as part of this study
      showed significant differences between field isolates and the Moroccan vaccine
      strain. New PCR methods were developed to differentiate between wild-type
      isolates and vaccine strains of SPPV. Using these methods, no trace of wild-type
      SPPV was found in the vaccine and no evidence was found to suggest that the
      vaccine strain was causing clinical disease.

PMID- 25753970
TI  - Attuning: A Communication Process between People with Severe and Profound
      Intellectual Disability and Their Interaction Partners.
AB  - BACKGROUND: People with severe and profound intellectual disability typically
      demonstrate a limited ability to communicate effectively. Most of their
      communications are non-verbal, often idiosyncratic and ambiguous. This article
      aims to identify the process that regulates communications of this group of
      people with others and to describe the methodological approach that was used to
      achieve this. MATERIALS AND METHODS: In this qualitative study, two dyads
      consisting of a person with severe or profound intellectual and multiple
      disability and a teacher or carer were filmed as they engaged in school-based
      activities. Two 1-hour videotapes were transcribed and analysed using grounded
      theory. RESULTS: Attuning was identified within the theory proposed here as a
      central process that calibrates and regulates communication. CONCLUSION: Attuning
      is conceptualized as a bidirectional, dyadic communication process. Understanding
      this process may support more effective communication between people with severe
      or profound intellectual and multiple disability and their interaction partners.

PMID- 25753971
TI  - A selectivity study of sodium-dependent glucose cotransporter 2/sodium-dependent
      glucose cotransporter 1 inhibitors by molecular modeling.
AB  - Sodium-dependent glucose cotransporters (SGLTs) play an important role in glucose
      reabsorption in the kidney and have been identified as promising targets to treat
      diabetes. Because of the side effects like glucose and galactose malabsorption by
      targeting SGLT1, highly selective SGLT2 inhibitors are more promising in the
      treatment of diabetes. To understand the mechanism of selectivity, we conducted
      selectivity-based three-dimensional quantitative structure-activity relationship
      studies to highlight the structure requirements for highly selective SGLT2
      inhibitors. The best comparative molecular field analysis and comparative
      molecular similarity indices analysis models showed the noncross-validated
      coefficient (r(2) ) of 0.967 and 0.943, respectively. The predicted correlation
      coefficients (r(2) pred ) of 0.974 and 0.938 validated the reliability and
      predictability of these models. Besides, homology models of SGLT2 and SGLT1 were
      also constructed to investigate the selective mechanism from structure-based
      perspective. Molecular dynamics simulation and binding free energy calculation
      were performed on the systems of a potent and selective compound interacting with
      SGLT2 and SGLT1 to compare the different binding modes. The simulation results
      showed that the stretch of the methylthio group on Met241 had an essential effect
      on the different binding modes between SGLT1 and SGLT2, which was consistent with
      the three-dimensional quantitative structure-activity relationship analysis.
      Hydrogen bond analysis and binding free energy calculation revealed that SGLT2
      binding complex was more stable and favorable than SGLT1 complex, which was
      highly correlated with the experimental results. Our obtained results give useful
      information for the investigation of the inhibitors' selectivity between SGLT2
      and SGLT1 and will help for further development of highly selective SGLT2
      inhibitors.

PMID- 25753973
TI  - Design and performance evaluation of a linear ion trap mass analyzer featuring
      half round rod electrodes.
AB  - A novel linear ion trap mass analyzer featuring half round rod electrodes
      (HreLIT) has been built. It is mainly composed of two pairs of stainless steel
      electrodes which have a cross-section of half round rod and a pair of end
      electrodes. The HreLIT has a simple structure and so it could be assembled by
      hand with relatively high mechanical accuracy. The external dimension of HreLIT
      is 50 mm * 29.5 mm * 28 mm (length * width * height) and its internal volume is
      about 3.8 cm(3). A home-made HreLIT mass spectrometer with three-stage vacuum
      system was built and the performance of HreLIT was characterized using reserpine
      solution and PPG standard solution. When the scan rate was 254 u/s, mass peak
      with FWHM of 0.14 u was achieved for ions with m/z 609, which corresponds to a
      mass resolution of 4350. The HreLIT was also operated at a low q value of 0.28 to
      extend its mass range. The experiment result showed a mass range of over 2800 u
      and the amplitude of radio frequency (rf) signal was only 1560 V (0-p). Three
      stage tandem mass spectrometry was successfully performed in the HreLIT, and the
      collision-induced dissociation (CID) efficiencies of MS(2) (CID of ions with m/z
      609) and MS(3) (CID of ions with m/z 448) were 78% and 59%, respectively. 

PMID- 25753972
TI  - Increasing protein charge state when using laser electrospray mass spectrometry.
AB  - Femtosecond (fs) laser vaporization is used to transfer cytochrome c, myoglobin,
      lysozyme, and ubiquitin from the condensed phase into an electrospray (ES) plume
      consisting of a mixture of a supercharging reagent, m-nitrobenzyl alcohol (m
      NBA), and trifluoroacetic acid (TFA), acetic acid (AA), or formic acid (FA).
      Interaction of acid-sensitive proteins like cytochrome c and myoglobin with the
      highly charged ES droplets resulted in a shift to higher charge states in
      comparison with acid-stable proteins like lysozyme and ubiquitin. Laser
      electrospray mass spectrometry (LEMS) measurements showed an increase in both the
      average charge states (Zavg) and the charge state with maximum intensity (Zmode)
      for acid-sensitive proteins compared with conventional electrospray ionization
      mass spectrometry (ESI-MS) under equivalent solvent conditions. A marked increase
      in ion abundance of higher charge states was observed for LEMS in comparison with
      conventional electrospray for cytochrome c (ranging from 19+ to 21+ versus 13+ to
      16+) and myoglobin (ranging from 19+ to 26+ versus 18+ to 21+) using an ES
      solution containing m-NBA and TFA. LEMS measurements as a function of
      electrospray flow rate yielded increasing charge states with decreasing flow
      rates for cytochrome c and myoglobin. 

PMID- 25753974
TI  - Association of sex hormones with carotid artery distensibility in men and
      postmenopausal women: multi-ethnic study of atherosclerosis.
AB  - The decline in carotid distensibility with age is steeper in women than in men,
      however, the correlates of this sex difference are not known. We examined the
      association of bioavailable testosterone, estradiol, dehydroepiandrosterone, and
      sex hormone-binding globulin, in 2783 postmenopausal women and 2987 men aged 45
      to 84 years at the Multi-Ethnic Study of Atherosclerosis baseline examination.
      Carotid artery lumen diameters by ultrasound and brachial artery blood pressures
      were measured at systole and diastole. Regression models to determine the
      association of carotid distensibility coefficient and lumen diameter with sex
      specific quartiles of sex hormones were adjusted for age, race, height, weight,
      diabetes mellitus, current smoking, antihypertensive medication use, total and
      high-density lipoprotein cholesterol levels, and hormone replacement therapy in
      women. A higher DC indicates a more distensible vessel. In women, higher
      dehydroepiandrosterone (P=0.008) and lower sex hormone-binding globulin (P=0.039)
      were associated with lower distensibility; higher dehydroepiandrosterone and
      lower estradiol were associated with smaller carotid diameters. In men, higher
      Bio-T (P=0.009) and lower estradiol (P=0.007) were associated with greater
      distensibility and also with smaller diameters (P=0.012 and 0.002, respectively).
      An androgenic internal milieu is associated with lesser carotid distensibility
      and diameter remodeling in women, but the opposite is true for men. Higher levels
      of estradiol are associated with smaller carotid diameters in both the sexes.
      Future longitudinal and experimental studies are needed to reveal the mechanism
      and clinical consequences of these associations. 

PMID- 25753975
TI  - Serotonin: a different player in hypertension-associated thrombosis.

PMID- 25753976
TI  - Relationship between daily exposure to biomass fuel smoke and blood pressure in
      high-altitude Peru.
AB  - Household air pollution from biomass fuel use affects 3 billion people worldwide;
      however, few studies have examined the relationship between biomass fuel use and
      blood pressure. We sought to determine if daily biomass fuel use was associated
      with elevated blood pressure in high altitude Peru and if this relationship was
      affected by lung function. We analyzed baseline information from a population
      based cohort study of adults aged >= 35 years in Puno, Peru. Daily biomass fuel
      use was self-reported. We used multivariable regression models to examine the
      relationship between daily exposure to biomass fuel smoke and blood pressure
      outcomes. Interactions with sex and quartiles of forced vital capacity were
      conducted to evaluate for effect modification. Data from 1004 individuals (mean
      age, 55.3 years; 51.7% women) were included. We found an association between
      biomass fuel use with both prehypertension (adjusted relative risk ratio, 5.0;
      95% confidence interval, 2.6-9.9) and hypertension (adjusted relative risk ratio,
      3.5; 95% confidence interval, 1.7-7.0). Biomass fuel users had a higher systolic
      blood pressure (7.0 mm Hg; 95% confidence interval, 4.4-9.6) and a higher
      diastolic blood pressure (5.9 mm Hg; 95% confidence interval, 4.2-7.6) when
      compared with nonusers. We did not find interaction effects between daily biomass
      fuel use and sex or percent predicted forced vital capacity for either systolic
      blood pressure or diastolic blood pressure. Biomass fuel use was associated with
      a higher likelihood of having hypertension and higher blood pressure in Peru.
      Reducing exposure to household air pollution from biomass fuel use represents an
      opportunity for cardiovascular prevention.

PMID- 25753977
TI  - Molecular-based mechanisms of Mendelian forms of salt-dependent hypertension:
      questioning the prevailing theory.
AB  - This critical review directly challenges the prevailing theory that a transient
      increase in cardiac output caused by genetically mediated increases in activity
      of the ENaC in the aldosterone sensitive distal nephron, or of the NCC in the
      distal convoluted tubule, accounts entirely for the hemodynamic initiation of all
      Mendelian forms of salt-dependent hypertension (Figure 1). The prevailing theory
      of how genetic mutations enable salt to hemodynamically initiate Mendelian forms
      of salt-dependent hypertension in humans (Figure 1) depends on the results of
      salt-loading studies of cardiac output and systemic vascular resistance in
      nongenetic models of hypertension that lack appropriate normal controls. The
      theory is inconsistent with the results of studies that include measurements of
      the initial hemodynamic changes induced by salt loading in normal, salt-resistant
      controls. The present analysis, which takes into account the results of salt
      loading studies that include the requisite normal controls, indicates that
      mutation-induced increases in the renal tubular activity of ENaC or NCC that lead
      to transient increases in cardiac output will generally not be sufficient to
      enable increases in salt intake to initiate the increased BP that characterizes
      Mendelian forms of salt-dependent hypertension (Table). The present analysis also
      raises questions about whether mutation-dependent increases in renal tubular
      activity of ENaC or NCC are even necessary to account for increased risk for salt
      dependent hypertension in most patients with such mutations. We propose that for
      the genetic alterations underlying Mendelian forms of salt-dependent hypertension
      to enable increases in salt intake to initiate the increased BP, they must often
      cause vasodysfunction, ie, an inability to normally vasodilate and decrease
      systemic vascular resistance in response to increases in salt intake within
      dietary ranges typically observed in most modern societies. A subnormal ability
      to vasodilate in response to salt loading could be caused by mutation-related
      disturbances originating in the vasculature itself or in sites outside the
      vasculature (eg, brain or adrenal glands) that have the capacity to affect
      vascular function.

PMID- 25753978
TI  - Streptococcus mutans and Streptococcus sobrinus colonization and caries
      experience in 3- and 5-year-old Thai children.
AB  - OBJECTIVES: The aim of this study was to examine the colonization of
      Streptococcus mutans and Streptococcus sobrinus in supra-gingival plaque samples
      and to determine their correlation with the prevalence of early childhood caries
      (ECC) in Thai children. MATERIALS AND METHODS: A total of 344 Thai children, ages
      3 and 5 years, were invited to participate in this study. Caries status of the
      children was examined. Supra-gingival plaque samples were collected. Quantitative
      real-time PCR was performed to evaluate DNA levels of S. mutans and S. sobrinus.
      RESULTS: Eighty-five percent of the children were colonized by S. mutans and
      50.9% of them were colonized by S. sobrinus. The prevalence of ECC was 43.8% and
      56.2% among 3- and 5-year-old children, respectively, and was significantly
      associated with the presence of S. mutans and S. sobrinus. The severity of ECC
      was significantly correlated with increased DNA levels of the two bacteria.
      Children who were positive for S. mutans and S. sobrinus (Sm+/Sb+) were 8 times
      or 44 times more likely to experience ECC than children who were Sm-/Sb + or were
      Sm-/Sb-. CONCLUSIONS: The study evidence further suggest that children colonized
      by both S. mutans and S. sobrinus are at the higher risk for ECC. CLINICAL
      RELEVANCE: Molecular-based qPCR can be used to detect and quantify S. mutans and
      S. sobrinus colonization for epidemiological and clinical studies for ECC risk
      assessment.

PMID- 25753980
TI  - Innovative practices in international partnership: medical undergraduate program
      in twin campuses of India and Malaysia.

PMID- 25753979
TI  - Salivary enzyme activity in anorexic persons-a controlled clinical trial.
AB  - OBJECTIVES: Patients with anorexia nervosa are at high risk for general and oral
      diseases. However, not all anorexic patients suffer from them, irrespective of
      the severity of their eating disorder. It is often speculated that differences in
      the saliva are important; however, little is known about salivary parameters in
      anorexic patients. The aim of the clinical trial was to evaluate stimulated and
      resting salivary flow rate and the activity of the following enzymes in both
      types of saliva: amylase, aspartate amino transferase (AST), alanine amino
      transferase (ALT), collagenase, lysozyme, peroxidase, serine and acidic
      proteases, and trypsin in persons with anorexia nervosa (AN) and to compare them
      with those of healthy controls. MATERIALS AND METHODS: Sixty-six subjects
      participated (28 patients with anorexia nervosa, 38 matched healthy controls).
      RESULTS: Regarding flow rate, stimulated and unstimulated levels were
      significantly lower in the AN group than in the controls. Activities of
      collagenase and AST in stimulated saliva were significantly higher in anorexic
      participants. In the AN group, changes due to salivary stimulation were found for
      the activity of acidic proteases, AST, and lysozyme. CONCLUSION: Reduced salivary
      flow might be one indicator of anorexia. Despite starvation and anorexia
      development, salivary key enzymes show physiological activity. This indicates a
      partial adaptation of the organism to severe condition during malnutrition.
      CLINICAL RELEVANCE: Further research is needed into possible role of reduced
      collagenase and transaminase activities in maintaining protection against
      external noxae and bacteria which might have impact on general oral health among
      patients with anorexia nervosa.

PMID- 25753981
TI  - The effect of knee arthroplasty on balancing ability in response to sudden
      unidirectional perturbation in the early postoperative period.
AB  - INTRODUCTION AND OBJECTIVE: Total knee arthroplasty (TKA) affects 1-3% of the
      entire population. The effectiveness of surgery and rehabilitation are of great
      significance. The goal of this study was to determine how different surgical
      methods (i.e., conventional and minimally invasive) influence balancing ability
      in response to sudden unidirectional perturbation during the first 12 weeks of
      the postoperative period. MATERIALS AND METHODS: The balancing capacity after
      sudden unidirectional (horizontal) perturbation of 10 patients who had undergone
      TKA operations via the conventional method and 10 patients who had undergone TKA
      operations via the minimally invasive method were examined before and six and 12
      weeks after TKA. Forty-five health age-matched participants composed the control
      group. The balancing capacities following unidirectional perturbation were
      characterised by the Lehr's damping ratio, which was calculated based on the
      results of the provocation tests that were performed with the patients standing
      on both the affected and non-affected limbs. RESULTS: In both patient groups, the
      Lehr's damping ratios increased during the postoperative period. However, in both
      patient groups, the Lehr's damping ratios calculated from the results of all
      three of the testing methods decreased compared to values obtained from the
      controls even at 12 weeks postoperatively. Six and 12 weeks after TKA, the Lehr's
      damping ratios of the patients who underwent operations utilising the minimally
      invasive exposure method were significantly higher than the values obtained from
      the patients who underwent operations by conventional exposure. DISCUSSION AND
      CONCLUSIONS: In both patient groups, the balancing capacities continuously
      improved over the first 12 weeks of the postoperative period, but the dynamic
      balancing capacities while standing on both limbs, on the affected limb and on
      the non-affected limb significantly differed from those of the controls. The
      balancing capacities of the patients who underwent the minimally invasive
      exposure procedures improved more rapidly than did the capacities of the patients
      who underwent operations utilising the conventional exposure method. This reduced
      balancing capacity should be considered when developing dynamic balancing
      abilities and abandoning therapeutic aids, and the difference in dynamic
      balancing abilities between the two patient groups should also be considered.

PMID- 25753982
TI  - Patients with Persistently Elevated PSA and Negative Results of TRUS-Biopsy: Does
      6-Month Treatment with Dutasteride can Indicate Candidates for Re-Biopsy. What is
      the Best of Saturation Schemes: Transrectal or Transperineal Approach?
AB  - To identify patients who actually need a re - biopsy, based on alterations in PSA
      readings after 6-month treatment with Dutasteride. We also sought to bring out
      the most beneficial re-biopsy scheme. We have reviewed the records of patients
      with persistently elevated PSA and at least one set of TRUS biopsies. Patients
      who were treated with alpha -blockers/Dutasteride combination were considered as
      the study group, while patients in control received alpha-blockers alone.
      Patients in both groups underwent re-biopsy 6 months later. The two protocols of
      re-biopsies were used at that time: 20-24 cores saturation transrectal (ST)) and
      >= 40 cores saturation transperineal template-guided (STT) biopsies. One hundred
      thirty-three patients were included in this study. In 86.7 % of the patients in
      the study group mean PSA decreased from 7.4 +/- 2.69 to 4.037 +/- 1.53 (p-0.001).
      The overall cancer detection rate was 29 % (n-39: 19 v/s 20, control and study
      groups, respectively). In the study group PSA decreased to 26.73 +/- 11.26 % in
      patients with cancer, compared with 40.54 +/- 13.3 % in patients without. It must
      be emphasized that STT-biopsies detected significantly more cancers (38.46 v/s
      20.59 %, p- 0.005). Mean cores number got to 21 +/- 2.45 and 45 +/- 5.65 in ST
      and STT biopsies, respectively. Six-month treatment with Dutasteride decreases
      PSA readings in 86.7 % of the patients. A PSA decline of less than 40% (cutoff)
      should be considered as an indicator for re-biopsy. Transperineal template-guided
      biopsies had a higher cancer detection rate.

PMID- 25753983
TI  - One-Year Neoadjuvant Endocrine Therapy in Breast Cancer.
AB  - The evaluation of the effects of 1-year endocrine therapy (NET) was aimed at. A
      retrospective analysis of 42 cases with 46 stage II-III invasive, hormone
      receptor-positive, HER2-negative breast cancers was performed. One-year NET was
      planned with letrozole (n = 33, postmenopausal group), or with goserelin plus
      letrozole (n = 7) or with goserelin plus tamoxifen (n = 2) (premenopausal group).
      Surgery was performed in accordance with the initial stage and the response to
      therapy. With regard to the tumor remaining in the surgical specimen, risk groups
      were constructed: Group 1: stage 0, pathological complete regression (pCR); Group
      2: stages IA-IIA; Group 3: stages >= IIB + cases with clinical progression. Due
      to local progression, NET was replaced by neoadjuvant chemotherapy in three
      patients (four tumors). In two postmenopausal patients, letrozole was replaced by
      tamoxifen because of the insufficient treatment effect. In 19/42 cases, breast
      conserving surgery was performed. Within Group 1, there was no cancer in four
      cases, while only DCIS remained in 2 (pCR: 13 %); Groups 2 and 3 comprised 25 and
      15 cases, respectively. The likeliness of a good response (Groups 1 and 2 vs.
      Group 3) to NET was increased by 7 % for every 1 % increase of the expression of
      ER (OR = 1.070; 95 % CI: 1.007-1.138, p = 0.029). Progression-free survival
      differed according to treatment response (p = 0.001). The post-therapy Ki67 value
      of <= 15 % had only a marginal effect on survival. No other associations were
      detected between the tumor characteristics and the therapeutic response or
      survival. Long-duration NET is effective and safe in cases of hormone-sensitive
      breast cancer.

PMID- 25753984
TI  - Molecular and Clinicopathological Aspects of Prostate Cancer in Bulgarian
      Probands.
AB  - To correlate the molecular data to the clinicopathological parameters in
      Bulgarian prostate cancer patients. PCA3 overexpression, TMPRSS2-ERG gene fusion,
      GSTP1 promoter hypermethylation, somatic mutations in the AR gene and the IVS1
      27G > A polymorphism in the KLF6 gene were studied. A total of 148 patients were
      analyzed: 16 aggressive PCa, 83 non-aggressive PCa, 25 BPH and 24 chronic
      inflammatory diseases. Real-time RT-PCR, DNA sequencing, and bisulfite conversion
      of DNA, were applied. All cases with aggressive PCa before treatment were tested
      positive for PCA3 overexpression, expression of a T2-ERG gene fusion product and
      GSTP1 promoter hypermethylation. No somatic mutations were detected in the AR
      gene and all patients showed normal KLF6-IVS1-27G > A genotype. The TMPRSS2-ERG
      positive status correlates with moderate to poorly differentiated prostate tumors
      and it is considered as unfavorable disease predictor. Positive GSTP1 promoter
      hypermethylation seems to be highly specific and the earliest epigenetic change
      in the prostate gland, which indicates the beginning of the pathological process.
      The appearance of positive molecular markers in blood was considered as a
      predictor of PCa dissemination. GSTP1 promoter hypermethylation was found as the
      earliest and a long-lasting epigenetic marker in blood samples of PCa patients,
      which makes it suitable as a marker for treatment follow-up. The molecular
      profile of prostate cancer needs to be strictly monitored during the course of
      disease treatment, which is of a great help in determining the patient's
      individual therapy response. 

PMID- 25753985
TI  - Genetically expanded cell-free protein synthesis using endogenous pyrrolysyl
      orthogonal translation system.
AB  - Cell-free protein synthesis offers a facile and rapid method for synthesizing,
      monitoring, analyzing, and purifying proteins from a DNA template. At the same
      time, genetic code expansion methods are gaining attention due to their ability
      to site-specifically incorporate unnatural amino acids (UAAs) into proteins via
      ribosomal translation. These systems are based on the exogenous addition of an
      orthogonal translation system (OTS), comprising an orthogonal tRNA, and
      orthogonal aminoacyl tRNA synthetase (aaRS), to the cell-free reaction mixture.
      However, these components are unstable and their preparation is labor-intensive,
      hence introducing a major challenge to the system. Here, we report on an approach
      that significantly reduces the complexity, effort and time needed to express UAA
      containing proteins while increasing stability and realizing maximal suppression
      efficiency. We demonstrate an endogenously introduced orthogonal pair that
      enables the use of the valuable yet insoluble pyrrolysyl-tRNA synthetase in a
      cell-free system, thereby expanding the genetic repertoire that can be utilized
      in vitro and enabling new possibilities for bioengineering. With the high
      stability and efficiency of our system, we offer an improved and accessible
      platform for UAA incorporation into proteins.

PMID- 25753986
TI  - Silicon-mediated changes in polyamines participate in silicon-induced salt
      tolerance in Sorghum bicolor L.
AB  - Silicon (Si) is generally considered a beneficial element for the growth of
      higher plants, especially under stress conditions, but the mechanisms remain
      unclear. Here, we tested the hypothesis that Si improves salt tolerance through
      mediating important metabolism processes rather than acting as a mere mechanical
      barrier. Seedlings of sorghum (Sorghum bicolor L.) growing in hydroponic culture
      were treated with NaCl (100 mm) combined with or without Si (0.83 mm). The result
      showed that supplemental Si enhanced sorghum salt tolerance by decreasing Na(+)
      accumulation. Simultaneously, polyamine (PA) levels were increased and ethylene
      precursor (1-aminocyclopropane-1-carboxylic acid: ACC) concentrations were
      decreased. Several key PA synthesis genes were up-regulated by Si under salt
      stress. To further confirm the role of PA in Si-mediated salt tolerance,
      seedlings were exposed to spermidine (Spd) or a PA synthesis inhibitor
      (dicyclohexylammonium sulphate, DCHA) combined with salt and Si. Exogenous Spd
      showed similar effects as Si under salt stress whereas exogenous DCHA eliminated
      Si-enhanced salt tolerance and the beneficial effect of Si in decreasing Na(+)
      accumulation. These results indicate that PAs and ACC are involved in Si-induced
      salt tolerance in sorghum and provide evidence that Si plays an active role in
      mediating salt tolerance.

PMID- 25753987
TI  - Reduction of Store-Operated Ca(2+) Entry Correlates with Endothelial Progenitor
      Cell Dysfunction in Atherosclerotic Mice.
AB  - The dysfunction of endothelial progenitor cells (EPCs) has been shown to prevent
      endothelial repair during the development of atherosclerosis (AS). Previous
      studies have revealed that store-operated calcium entry (SOCE) is an important
      factor in regulating EPC functions. However, whether this is also the mechanism
      in AS has not been elucidated. Therefore, we evaluated the role of SOCE in EPCs
      isolated from an atherosclerotic mouse model. Atheromatous plaques were more
      frequent in the aortas of ApoE(-/-) mice fed a high-fat diet for 16 weeks
      compared with controls, and the proliferative and migratory activities of
      atherosclerotic EPCs were significantly decreased. Accordingly, SOCE amplitude,
      as well as spontaneous or VEGF-induced Ca(2+) oscillations, decreased in
      atherosclerotic EPCs. These results may be associated with the downregulated
      expression of Stim1, Orai1, and TRPC1, which are major mediators of SOCE. In
      addition, eNOS expression and phosphorylation at Ser(1177), which are critical
      regulators of EPC function, were markedly reduced in the atherosclerotic EPCs.
      The impairment of eNOS activity could also be induced by using an SOCE inhibitor
      or by Stim1 gene silencing, indicating a link between the activities of eNOS and
      SOCE in AS. Furthermore, decreased SOCE function inhibited EPC proliferation and
      migration in vitro. In conclusion, our results showed that the reduction of SOCE
      induced EPC dysfunction during AS, potentially through downregulation of store
      operated calcium channel (SOCC) components and impaired eNOS activity. Approaches
      aimed at reestablishing SOCE activity may thus improve the function of EPCs
      during AS. 

PMID- 25753988
TI  - Increased duodenal iron absorption through up-regulation of divalent metal
      transporter 1 from enhancement of iron regulatory protein 1 activity in patients
      with nonalcoholic steatohepatitis.
AB  - Increased hepatic iron accumulation is thought to be involved in the pathogenesis
      of nonalcoholic steatohepatitis (NASH). Hepatic iron accumulation, as well as
      oxidative DNA damage, is significantly increased in NASH livers. However, the
      precise mechanism of iron accumulation in the NASH liver remains unclear. In this
      study, 40 cases with a diagnosis of NASH (n = 25) or simple steatosis (SS; n =
      15) by liver biopsy were enrolled. An oral iron absorption test (OIAT) was used,
      in which 100 mg of sodium ferrous citrate was administered to each individual.
      The OIAT showed that absorption of iron from the gastrointestinal (GI) tract was
      increased significantly in NASH patients, compared to SS and control subjects.
      Iron reduction therapy was effective in patients with NASH, who exhibited iron
      deposition in the liver and no alanine aminotransferase improvement after other
      therapies (n = 9). Serum hepcidin concentration and messenger RNA (mRNA) levels
      of divalent metal transporter 1 (DMT1) also were significantly elevated in
      patients with NASH. OIAT results were correlated with grade of liver iron
      accumulation and DMT1 mRNA levels. Then, we demonstrated that DMT1 mRNA levels
      increased significantly in Caco-2/TC7 cell monolayers cultured in transwells with
      serum from NASH patients. An electrophoresis mobility shift assay showed
      activation of iron regulatory protein (IRP) in those cells, and IRP1 small
      interfering RNA clearly inhibited the increase of DMT1 mRNA levels. CONCLUSION:
      In spite of elevation of serum hepcidin, iron absorption from the GI tract
      increased through up-regulation of DMT1 by IRP1 activation by humoral factor(s)
      in sera of patients with NASH.

PMID- 25753989
TI  - Antibacterial photodynamic treatment of periodontopathogenic bacteria with
      indocyanine green and near-infrared laser light enhanced by Trolox(TM).
AB  - BACKGROUND AND OBJECTIVES: It has been shown that certain vitamins can
      significantly enhance the effect of photodynamic anti-tumor therapy.
      Unfortunately, there is no sufficient information available about the impact of
      those antioxidants on antimicrobial Photodynamic Therapy (aPDT). The present
      study is aimed at investigating the antimicrobial effect of the dye indocyanine
      green (ICG) in the presence of Trolox(TM) , a vitamin E analogue, upon
      irradiation with near-infrared (NIR) laser light (808 nm) on the gramnegative
      periodontopathogenic bacteria Aggregatibacter actinomycetemcomitans (A.a.),
      Porphyromonas gingivalis (P.g.) and Fusobacterium nucleatum (F.n.). METHODS:
      Bacteria solved in PBS were incubated with ICG (50-500 MUg/ml) in the presence
      and absence of Trolox(TM) (2 mM). Irradiation was performed after 10 minutes of
      dark-incubation with NIR-laser-light (25-100 J/cm(2) , 810 nm). During treatment,
      temperature was also recorded inside the bacterial solutions. The treated
      suspensions were serial diluted and plated onto blood agar plates. After anaerobe
      cultivation for 5 days the colony-forming units (CFU/ml) were determined.
      RESULTS: The antibacterial effect was ICG-concentration and exposure dependent.
      It was found that high ICG-concentrations and light fluence rates caused
      bacterial reduction due to hyperthermia. Where low ICG-concentrations (<250
      MUg/ml) and fluence rates only induced minor regression, additional Trolox(TM) 
      administration significantly enhanced the photodynamic effect. While treatment of
      A.a. (250 MUg/ml ICG, 100 J/cm(2) ) without Trolox(TM) caused no bacterial
      reduction, additional administration led to total eradication. In the presence of
      Trolox(TM) reduction to one-fifth of the original ICG-concentration (50 MUg/ml)
      still induced total suppression of P.g. and F.n. at identical fluence (100
      J/cm(2) ). Treatment with ICG, NIR-light or Trolox(TM) alone showed no remarkable
      bactericidal effect. Application of high ICG-concentrations (500 MUg/ml) and
      exposure values (100 J/cm(2) ) caused peak temperatures of 64.53 degrees C.
      CONCLUSIONS: The results clearly show that Trolox(TM) significantly enhanced the
      antibacterial effect of ICG upon irradiation with NIR-laser-light. Additional
      administration of Trolox(TM) may also increase the efficiency of other aPDT
      systems.

PMID- 25753990
TI  - Bacterial community dynamics during polysaccharide degradation at contrasting
      sites in the Southern and Atlantic Oceans.
AB  - The bacterial degradation of polysaccharides is central to marine carbon cycling,
      but little is known about the bacterial taxa that degrade specific marine
      polysaccharides. Here, bacterial growth and community dynamics were studied
      during the degradation of the polysaccharides chitin, alginate and agarose in
      microcosm experiments at four contrasting locations in the Southern and Atlantic
      Oceans. At the Southern polar front, chitin-supplemented microcosms were
      characterized by higher fractions of actively growing cells and a community shift
      from Alphaproteobacteria to Gammaproteobacteria and Bacteroidetes. At the
      Antarctic ice shelf, chitin degradation was associated with growth of
      Bacteroidetes, with 24% higher cell numbers compared with the control. At the
      Patagonian continental shelf, alginate and agarose degradation covaried with
      growth of different Alteromonadaceae populations, each with specific temporal
      growth patterns. At the Mauritanian upwelling, only the alginate hydrolysis
      product guluronate was consumed, coincident with increasing abundances of
      Alteromonadaceae and possibly cross-feeding SAR11. 16S rRNA gene amplicon
      libraries indicated that growth of the Bacteroidetes-affiliated genus
      Reichenbachiella was stimulated by chitin at all cold and temperate water
      stations, suggesting comparable ecological roles over wide geographical scales.
      Overall, the predominance of location-specific patterns showed that bacterial
      communities from contrasting oceanic biomes have members with different
      potentials to hydrolyse polysaccharides. 

PMID- 25753992
TI  - If you have something to say, you can say it....

PMID- 25753991
TI  - pH-responsive artemisinin dimer in lipid nanoparticles are effective against
      human breast cancer in a xenograft model.
AB  - Artemisinin (ART), a well-known antimalaria drug, also exhibits anticancer
      activities. We previously reported a group of novel dimeric artemisinin
      piperazine conjugates (ADPs) possessing pH-dependent aqueous solubility and a
      proof-of-concept lipid nanoparticle formulation based on natural egg
      phosphatidylcholine (EPC). EPC may induce allergic reactions in individuals
      sensitive to egg products. Therefore, the goal of this report is to develop ADP
      synthetic lipid particles suitable for in vivo evaluation. We found that ADP
      binds to 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) with greater than 90%
      efficiency and forms drug-lipid particles (d ~ 80 nm). Cryo-electron microscopy
      of the ADP drug-lipid particles revealed unilamellar vesicle-like structures.
      Detailed characterization studies show insertion of the ADP lead compound,
      ADP109, into the DPPC membrane and the presence of an aqueous core. Over 50% of
      the ADP109 was released in 48 hours at pH4 compared with less than 20% at
      neutral. ADP109-lipid particles exhibited high potency against human breast
      cancer, but was tolerated well by nontumorigenic cells. In MDA-MB-231 mouse
      xenograft model, lipid-bound ADP109 particles were more effective than paclitaxel
      in controlling tumor growth. Cellular uptake studies showed endocytosis of the
      nanoparticles and release of core-trapped marker throughout the cytosol at 37
      degrees C. These results demonstrate, for the first time, the in vivo feasibility
      of lipid-bound ART dimer for cancer chemotherapy.

PMID- 25753993
TI  - An investigation into the detection of latent marks on the feathers and eggs of
      birds of prey.
AB  - There are numerous enhancement techniques (physical and chemical) which have been
      developed for the successful visualisation of latent fingermarks. Nonetheless,
      problems arise when latent fingermarks require enhancement on difficult surfaces
      such as human skin, food stuffs, fabric and animals. The ability to develop
      latent fingermarks on the surface of bird of prey feathers and that of their eggs
      was investigated. Red and green magnetic fluorescent powders proved to be most
      suitable on the surface of bird of prey feathers whereas black magnetic powder
      was the most suitable technique on the eggs. These powders produced the highest
      quality of visible ridge-detailed developments over a controlled period of time. 

PMID- 25753994
TI  - Fingermark recovery from riot debris: Bricks and stones.
AB  - During the UK riots in August 2011, large volumes of bricks and stones were used
      as weapons or projectiles in acts of violence or to gain illegal entry to
      properties. As a result, it has been emphasised that it is necessary to determine
      suitable chemical treatment(s) that will enable the development of fingermarks on
      such items in order to identify those involved. This study has undertaken the
      task of attempting to develop latent fingermarks on common house bricks,
      limestone and sandstone using current techniques including ninhydrin and
      fluorescence. Results produced have shown that, with fluorescent fingerprint
      powder, silver nitrate and superglue providing the best results, it is now
      possible to enhance fingermarks that were previously left undeveloped. In
      addition, Isomark T-1 Rapid Grey High Resolution Forensic Impression Material has
      proved extremely effective as an alternative method of recovering fingermarks
      developed with fluorescent fingerprint powder. 

PMID- 25753995
TI  - The prevalence of two 'commonly' encountered synthetic target fibres within a
      large urban environment.
AB  - A target fibre study was carried out to assess the random prevalence of two
      ostensibly commonly encountered synthetic fibre types; black acrylic and blue
      polyester. The study was performed in an environment which maximised the number
      of random contacts between textile garments in the population and specific
      surfaces, namely; seating relating to buses, public houses and cinemas found
      within a large urban conurbation. Surface debris tapings were collected from
      samples of bus seats (30), pub seats (54) and cinema seats (53). Using low power
      stereomicroscopy, a total of 114 and 68 fibres, superficially similar to the
      respective black acrylic and blue polyester target fibres, were recovered from
      these tapings. The full range of comparative microscopical and instrumental
      analysis used in operational forensic laboratories was performed on the recovered
      fibres. No matches were found with either of the target fibres. These findings
      are in accordance with similar studies which show that the probability of an
      'adventitious' match with a particular fibre type/colour combination is extremely
      low. In addition, the findings demonstrate that the current techniques and
      instrumentation employed by operational forensic laboratories are fit for
      purpose. Importantly, the findings demonstrate that databases and surveys (e.g.
      fibre population studies) which do not consider the analytical/comparison
      processes, must not be used in isolation when evaluating fibre evidence at source
      level. 

PMID- 25753996
TI  - A methodology to event reconstruction from trace images.
AB  - The widespread use of digital imaging devices for surveillance (CCTV) and
      entertainment (e.g., mobile phones, compact cameras) has increased the number of
      images recorded and opportunities to consider the images as traces or
      documentation of criminal activity. The forensic science literature focuses
      almost exclusively on technical issues and evidence assessment [1]. Earlier steps
      in the investigation phase have been neglected and must be considered. This
      article is the first comprehensive description of a methodology to event
      reconstruction using images. This formal methodology was conceptualised from
      practical experiences and applied to different contexts and case studies to test
      and refine it. Based on this practical analysis, we propose a systematic approach
      that includes a preliminary analysis followed by four main steps. These steps
      form a sequence for which the results from each step rely on the previous step.
      However, the methodology is not linear, but it is a cyclic, iterative progression
      for obtaining knowledge about an event. The preliminary analysis is a pre
      evaluation phase, wherein potential relevance of images is assessed. In the first
      step, images are detected and collected as pertinent trace material; the second
      step involves organising and assessing their quality and informative potential.
      The third step includes reconstruction using clues about space, time and actions.
      Finally, in the fourth step, the images are evaluated and selected as evidence.
      These steps are described and illustrated using practical examples. The paper
      outlines how images elicit information about persons, objects, space, time and
      actions throughout the investigation process to reconstruct an event step by
      step. We emphasise the hypothetico-deductive reasoning framework, which
      demonstrates the contribution of images to generating, refining or eliminating
      propositions or hypotheses. This methodology provides a sound basis for extending
      image use as evidence and, more generally, as clues in investigation and crime
      reconstruction processes. 

PMID- 25753997
TI  - Semen searching when sperm is absent.
AB  - Sexual assault cases have varying factors that may mask semen findings when
      analysing evidence at the forensic laboratory. Semenogelin (Sg) is a potential
      marker for the identification of semen even at azoospermy or when few sperm cells
      are found. The current study examined Sg in normospermic and azoospermic donors
      as an internal evaluation of sensitivity, specificity and interference. The
      impact of a historical review of 53 judicial sexual assault cases over a five
      year period was also analysed. The use of varying tests was of importance to
      prioritize certain samples within cases. Semen findings by Sg were then compared
      to prostate-specific antigen (PSA), phosphatase enzyme (AP) and Y-chromosome
      presence, the latter being used in an attempt to link semen fluid identification
      with obtaining a male DNA profile. Test findings were the highest ever registered
      for Sg (1:400,000), PSA (1:800,000), AP (1:25,000) and sperm cytology (SC)
      (1:50,000). Our results demonstrated the usefulness of using the Sg marker to
      avoid a false semen-negative result (6% cases), particularly in cases where sperm
      was absent or scarce (11% spermatozoa positive cases). Results were expressed in
      categories according to the set: Sg-PSA-AP. Thus, categories I (full positive,
      46%), VI (full negative, 27%) and III (Sg/PSA positive; 11%) were the most
      frequent and Y-chromosome was obtained in 59%, 12% and 12% ratios, respectively.
      In conclusion, Sg was recommended for the workflow procedure of semen
      investigation when sperm absence is expected either from azoospermic/oligospermic
      or normospermic semen, especially before/after ejaculation. 

PMID- 25753998
TI  - A potential new diagnostic tool to aid DNA analysis from heat compromised bone
      using colorimetry: A preliminary study.
AB  - Extracting viable DNA from many forensic sample types can be very challenging, as
      environmental conditions may be far from optimal with regard to DNA preservation.
      Consequently, skeletal tissue can often be an invaluable source of DNA. The bone
      matrix provides a hardened material that encapsulates DNA, acting as a barrier to
      environmental insults that would otherwise be detrimental to its integrity.
      However, like all forensic samples, DNA in bone can still become degraded in
      extreme conditions, such as intense heat. Extracting DNA from bone can be
      laborious and time-consuming. Thus, a lot of time and money can be wasted
      processing samples that do not ultimately yield viable DNA. We describe the use
      of colorimetry as a novel diagnostic tool that can assist DNA analysis from heat
      treated bone. This study focuses on characterizing changes in the material and
      physical properties of heated bone, and their correlation with digitally measured
      color variation. The results demonstrate that the color of bone, which serves as
      an indicator of the chemical processes that have occurred, can be correlated with
      the success or failure of subsequent DNA amplification. 

PMID- 25753999
TI  - Chemical Differentiation of Osseous, Dental, and Non-skeletal Materials in
      Forensic Anthropology using Elemental Analysis.
AB  - Forensic anthropologists are generally able to identify skeletal materials (bone
      and tooth) using gross anatomical features; however, highly fragmented or
      taphonomically altered materials may be problematic to identify. Several chemical
      analysis techniques have been shown to be reliable laboratory methods that can be
      used to determine if questionable fragments are osseous, dental, or non-skeletal
      in nature. The purpose of this review is to provide a detailed background of
      chemical analysis techniques focusing on elemental compositions that have been
      assessed for use in differentiating osseous, dental, and non-skeletal materials.
      More recently, chemical analysis studies have also focused on using the elemental
      composition of osseous/dental materials to evaluate species and provide
      individual discrimination, but have generally been successful only in small,
      closed groups, limiting their use forensically. Despite significant advances
      incorporating a variety of instruments, including handheld devices, further
      research is necessary to address issues in standardization, error rates, and
      sample size/diversity. 

PMID- 25754000
TI  - Examination of ossification of the distal radial epiphysis using magnetic
      resonance imaging. New insights for age estimation in young footballers in FIFA
      tournaments.
AB  - Alongside a variety of clinical and forensic issues, age determination in living
      persons also plays a decisive role in the field of professional sport. Only
      methods of determining skeletal age which do not expose individuals to ionizing
      radiation are suitable for this purpose. The present study examines whether MRI
      diagnosis of the distal radial epiphysis can be utilised to monitor
      internationally relevant age limits in professional football. The wrist area of
      152 male footballers aged 18 to 22 years belonging to regional clubs was
      prospectively examined using MRI. The ossification stage of the distal radial
      epiphysis was subsequently determined on the basis of established criteria used
      in determining the maturity of the medial clavicular epiphysis. For the first
      time, we ascertained evidence of an increase in the prevalence of the phenomenon
      of threefold linear stratification (hypointense line, hyperintense line, and
      hypointense line) in the representation of the fused epiphyseal plate of the
      radius using magnetic resonance imaging with increasing chronological age. Within
      our study population, test persons with an ossified epiphyseal plate without any
      verifiable epiphyseal scar were not represented. The presumably high minimum age
      of entry into this final stage of development (>22 years) must be verified in the
      course of further studies. According to the results of the present study, the
      fused epiphyseal plate of the distal radius provides potential maturation
      criteria which appear suitable for reliable monitoring of all relevant age limits
      in international football with the aid of magnetic resonance imaging.

PMID- 25754001
TI  - The communication of forensic science in the criminal justice system: A review of
      theory and proposed directions for research.
AB  - Clear communication about forensic science is essential to the effectiveness and
      perceived trustworthiness of the criminal justice system. Communication can be
      seen as a meaning-making process that involves different components such as the
      sender of a message, the message itself, the channel in which a message is sent,
      and the receiver of the message. Research conducted to date on the communication
      between forensic scientists and non-scientists in the criminal justice system has
      focused on different components of the communication process as objects of study.
      The purpose of this paper is to bring together communication theory and past
      research on the communication of forensic science to contribute to a deeper
      understanding of it, and to provide a coherent view of it overall. The paper
      first outlines the broader context of communication theory and science
      communication as a backdrop to forensic science communication. Then it presents a
      conceptual framework as a way to organise past research and, using the framework,
      reviews recent examples of empirical research and commentary on the communication
      of forensic science. Finally the paper identifies aspects of the communication of
      forensic science that may be addressed by future research to enhance the
      effectiveness of communication between scientists and non-scientists in this
      multidisciplinary arena. 

PMID- 25754002
TI  - Cognitive fallacies and criminal investigations.
AB  - The human mind is susceptible to inherent fallacies that often hamper fully
      rational action. Many such misconceptions have an evolutionary background and are
      thus difficult to avert. Deficits in the reliability of eye-witnesses are well
      known to legal professionals; however, less attention has been paid to such
      effects in crime investigators. In order to obtain an "inside view" on the role
      of cognitive misconceptions in criminalistic work, a list of fallacies from the
      literature was adapted to criminalistic settings. The statements on this list
      were rated by highly experienced crime scene investigators according to the
      assumed likelihood of these errors to appear and their severity of effect. Among
      others, selective perception, expectation and confirmation bias, anchoring/"pars
      per toto" errors and "onus probandi"--shifting the burden of proof from the
      investigator to the suspect--were frequently considered to negatively affect
      criminal investigations. As a consequence, the following measures are proposed:
      alerting investigating officers in their training to cognitive fallacies and
      promoting the exchange of experiences in peer circles of investigators on a
      regular basis. Furthermore, the improvement of the organizational error culture
      and the establishment of a failure analysis system in order to identify and
      alleviate error prone processes are suggested.

PMID- 25754003
TI  - Multiproblem Families Referred to Youth Mental Health: What's in a Name?
AB  - The purpose of this study was threefold, namely (1) to differentiate between
      multiproblem families and control families on characteristics and processes
      within the family based on a theoretical framework, (2) to identify multiproblem
      families by establishing cut-off scores on various questionnaires, and (3) to
      categorize multiproblem families into subtypes by cluster analyses. Various
      questionnaires were administered to multiproblem families (n = 85) and control
      families (n = 150). Results showed that what we propose to refer to as
      multiproblem families present a broad range of problems on seven domains: (1)
      child factors, (2) parental factors, (3) childrearing problems (inadequate or
      inconsistent parenting), (4) family functioning problems, (5) contextual
      problems, (6) social network problems, and (7) mental health care problems.
      Further, reliable cut-off scores were established for various questionnaires.
      Finally, three types of families were found: (1) community-problem families, (2)
      multiproblem families, and (3) child-focused mild-problem families. This paper
      looks to advance an evidence-based definition and assessment of "multiproblem
      families" suggesting the possible value of defining and assessing multiproblem
      families in relation to these seven dimensions. Moreover, the classification of
      multiproblem families stresses the importance of providing tailored treatments.

PMID- 25754004
TI  - Toward further prevention of bleeding after gastric endoscopic submucosal
      dissection.

PMID- 25754005
TI  - Hurdles of duodenal endoscopic submucosal dissection, delayed bleeding and
      perforation.

PMID- 25754006
TI  - Non-polypoid colorectal neoplasms are no longer unique to Japan, but do not mix
      up flat and depressed lesions.

PMID- 25754007
TI  - Intravenous zinc therapy for acquired zinc deficiency secondary to gastric bypass
      surgery: a case report.
AB  - Zinc deficiency may result from either a congenitally inherited defect of zinc
      absorption or is acquired secondarily from a variety of factors affecting dietary
      zinc intake, absorption, or loss. We report a case of acquired zinc deficiency
      secondary to gastric bypass surgery that resulted in vulvar cutaneous
      manifestations of delayed onset, with failure to clear after oral supplementation
      with zinc. The patient experienced improvement of symptoms only after
      administration of intravenous zinc supplementation. Upon review of the current
      literature, it is thought that the patient's original suboptimal response to oral
      supplementation and improvement after receiving intravenous zinc were related to
      the intentional surgical alteration and bypass of the absorptive capacity of the
      duodenum and jejunum. With the current prevalence of obesity and availability of
      surgical weight loss therapies, it is important to be mindful of the resulting
      nutritional deficiencies, their clinical manifestations, and factors affecting
      the efficacy of therapeutic approaches as seen in this case. 

PMID- 25754008
TI  - Wavefront-optimized laser in situ keratomileusis with the Allegretto Wave Eye-Q
      excimer laser and the FEMTO LDV Crystal Line femtosecond laser: 6 month visual
      and refractive results.
AB  - PURPOSE: To present the first reported series of patients undergoing myopic LASIK
      with the FEMTO LDV Crystal Line femtosecond laser and the WaveLight Allegretto
      Eye-Q excimer laser. We report the uncorrected and corrected distance visual
      acuity (UDVA and CDVA), refractive predictability, efficacy and safety of laser
      in situ keratomileusis (LASIK) performed with the above laser platforms. METHODS:
      This prospective interventional case series study evaluated consecutive eyes with
      low to moderate myopic astigmatism that underwent LASIK with the FEMTO LDV
      Crystal Line femtosecond laser and the WaveLight Allegretto Eye-Q 400 Hz excimer
      laser. Visual and refractive changes as well as complications were evaluated
      after wavefront-optimized laser treatment. RESULTS: Four hundred and forty four
      patients (887 eyes) reached the 6-month time gate. Mean age at time of procedure
      was 31 years (range: 20-59). Mean pre-op spherical-equivalent (SE) was -3.44
      diopters (D)+/-1.34D (range: -0.50 to -7.00) whilst the postoperative spherical
      equivalent decreased to -0.08+/-0.31D (range -2.25 to 1.00). At 6-month follow
      up, 96.9% of patients had monocular uncorrected distance visual acuity of 20/20
      or better with 95.2% of patients within +/-0.5D of intended refractive outcome.
      All patients achieved 20/20 binocular distance uncorrected visual acuity. No
      significant intra-operative or postoperative complications were encountered
      during the 6-month follow-up period. CONCLUSIONS: The combination of the above
      laser platforms provides safe, effective and predictable results in correcting
      compound myopic astigmatism with excellent visual outcomes.

PMID- 25754009
TI  - The role of Drosophila TNF Eiger in developmental and damage-induced neuronal
      apoptosis.
AB  - Eiger, the sole Drosophila TNF-alpha homolog, causes ectopic apoptosis through
      JNK pathway activation. Yet, its role in developmental apoptosis remains unclear.
      eiger mutant flies are viable and fertile but display compromised elimination of
      oncogenic cells and extracellular bacteria. Here we show that Eiger, specifically
      expressed in embryonic neurons and glia, is not involved in developmental
      neuronal apoptosis or in apoptotic cell clearance. Instead, we provide evidence
      that Eiger is required for damage-induced apoptosis in the embryonic CNS through
      regulation of the pro-apoptotic gene hid independently of the JNK pathway. Our
      study thus reveals a new requirement for Eiger in eliminating damaged cells
      during development. 

PMID- 25754010
TI  - Occurrence and potential transfer of mycotoxins in gilthead sea bream and
      Atlantic salmon by use of novel alternative feed ingredients.
AB  - Plant ingredients and processed animal proteins (PAP) are suitable alternative
      feedstuffs for fish feeds in aquaculture practice, although their use can
      introduce contaminants that are not previously associated with marine salmon and
      gilthead sea bream farming. Mycotoxins are well known natural contaminants in
      plant feed material, although they also could be present on PAPs after fungi
      growth during storage. The present study surveyed commercially available plant
      ingredients (19) and PAP (19) for a wide range of mycotoxins (18) according to
      the EU regulations. PAP showed only minor levels of ochratoxin A and fumonisin B1
      and the mycotoxin carry-over from feeds to fillets of farmed Atlantic salmon and
      gilthead sea bream (two main species of European aquaculture) was performed with
      plant ingredient based diets. Deoxynivalenol was the most prevalent mycotoxin in
      wheat, wheat gluten and corn gluten cereals with levels ranging from 17 to 814
      and MUg kg(-1), followed by fumonisins in corn products (range 11.1-4901 MUg kg(
      1) for fumonisin B1+B2+B3). Overall mycotoxin levels in fish feeds reflected the
      feed ingredient composition and the level of contaminant in each feed ingredient.
      In all cases the studied ingredients and feeds showed levels of mycotoxins below
      maximum residue limits established by the Commission Recommendation 2006/576/EC.
      Following these guidelines no mycotoxin carry-over was found from feeds to edible
      fillets of salmonids and a typically marine fish, such as gilthead sea bream. As
      far we know, this is the first report of mycotoxin surveillance in farmed fish
      species.

PMID- 25754011
TI  - BTEX in vitro exposure tool using human lung cells: trips and gains.
AB  - Cytotoxicity of benzene, toluene, ethylbenzene and xylenes (BTEX) to human lung
      cells was explored using three different exposure methods: Method 1 - in normal
      96-well plates using DMSO as a carrier vehicle, we exposed (a) human lung
      carcinoma A549 cells, (b) A549 cells over-expressed with cytochrome P450 2E1
      cells, and (c) normal lung fibroblast LL-24 cells to benzene, toluene,
      ethylbenzene and xylene individually and in a mixture which models car exhaust
      gases for between 1-88 h. We found that the order of the BTEX potency is
      benzene<toluene<ethylbenzene=m-xylene with acute BTEX toxicity to A549~LL
      24>CYP2E1 over-expressed A549 cells. A significant difference was found between
      inter-assay responses for all 24h exposures (P<0.005) suggesting a poor assay
      repeatability. No sign of potency increase was found from 6 to 72 h exposures.
      Method 2 - Using sealed vials to expose A549 cells to benzene, toluene and
      ethylbenzene, we observed a twenty-fold increase in their cytotoxicity, but also
      with no time-course effect. Method 3 - Using air exposed hanging-drop cell
      culture, we were able to see both an increase of demonstration of toxicity and a
      time-course effect from 1 to 12h exposure. We conclude that exposing cells in
      sealed and unsealed media using DMSO as a carrier vehicle was not suitable for
      BTEX exposure studies. Hanging-drop air exposure has more potential. It should be
      noted that if there are any changes in their exposure matrixes, its exposure mass
      distribution in cells could differ.

PMID- 25754012
TI  - Estrogen mimics induce genes encoding chemical efflux proteins in gram-negative
      bacteria.
AB  - Escherichia coli and Pseudomonas aeruginosa are gram-negative bacteria found in
      wastewater and biosolids. Spanning the inner and outer membrane are resistance
      nodulation-cell division superfamily (RND) efflux pumps responsible for
      detoxification of the cell, typically in response to antibiotics and other
      toxicity inducing substrates. Here, we show that estrogenic endocrine disruptors,
      common wastewater pollutants, induce genes encoding chemical efflux proteins.
      Bacteria were exposed to environmental concentrations of the synthetic estrogen
      17alpha-ethynylestradiol, the surfactant nonylphenol, and the plasticizer
      bisphenol-A, and analyzed for RND gene expression via q-PCR. Results showed that
      the genes acrB and yhiV were over-expressed in response to the three chemicals in
      E. coli, and support previous findings that these two transporters export
      hormones. P. aeruginosa contains 12 RND efflux pumps, which were differentially
      expressed in response to the three chemicals: 17alpha-ethynylestradiol, bisphenol
      A, and nonylphenol up-regulated mexD and mexF, while nonylphenol and bisphenol-A
      positively affected transcription of mexK, mexW, and triC. Gene expression via q
      PCR of RND genes may be used to predict the interaction of estrogen mimics with
      RND genes. One bacterial response to estrogen mimic exposure is to induce gene
      expression of chemical efflux proteins, which leads to the expulsion of the
      contaminant from the cell. 

PMID- 25754013
TI  - Evaluation of phytotoxicity and ecotoxicity potentials of a cyanobacterial
      extract containing microcystins under realistic environmental concentrations and
      in a soil-plant system.
AB  - The impact of a crude extract of Microcystis aeruginosa (PCC7820) containing 14
      microcystin variants was investigated on seeds germination and radicles
      development of four agricultural plants: two tomato varieties Solanum
      lycopersicum (MicroTom and Saint-Pierre), the wheat Triticum aestivum and the
      lettuce Lactuca sativa. In addition, the effect of 14 d-exposure to irrigation
      water containing realistic concentrations of microcystins (0-0.1 mg eq.
      microcystin-LRL(-1)) on the tomato MicroTom seedling growth was further evaluated
      on roots and aerial part biomasses. Impacts on soil bacterial parameters, as such
      extracellular enzymatic activities, nitrification activity and abundances of
      ammonia-oxidizing microorganisms were also investigated. In germination-test, the
      cyanobacterial extract inhibited only the germination of the wheat seeds, with an
      EC50 of 11 mg eq. microcystin-LRL(-1); which is 13 times lower than that of the
      cadmium chloride (EC50 of 145 mg L(-1)). Moreover, the cyanobacterial extract
      containing low concentrations of microcystins increased the growth of primary
      roots; however, high concentrations decreased it for all plants except for the
      wheat. In the soil-plant approach, only aerial part biomass of the tomato
      MicroTom was enhanced significantly. In addition, only soil nitrification
      potential and ammonia-oxidizing bacterial abundances were consistently impacted.
      A significant positive correlation (r=0.56) was found between the increase of
      nitrification potential and abundances of ammonia-oxidizing bacteria. This work
      suggested, that exposure to a cyanobacterial extract containing realistic
      environmental microcystins concentrations could affect seed germination,
      depending plant species. It was also highlighted, for the first time,
      disturbances in soil bacteria functioning, evidences on soil nitrification
      process.

PMID- 25754014
TI  - A ratiometric fluorescent molecular probe for visualization of mitochondrial
      temperature in living cells.
AB  - Mitochondrial thermodynamics is the key to understand cellular activities related
      to homeostasis and energy balance. Here, we report the first ratiometric
      fluorescent molecular probe (Mito-RTP) that is selectively localized in the
      mitochondria and visualize the temperature. We confirmed that Mito-RTP could work
      as a ratiometric thermometer in a cuvette and living cells. 

PMID- 25754015
TI  - [Lesson of graveyards].

PMID- 25754016
TI  - Role of enhanced half-life factor VIII and IX in the treatment of haemophilia.
AB  - Treatment of congenital haemophilia with factor VIII and IX concentrates often
      requires frequent infusions. This has obvious implications in establishing
      effective administration strategies and, in turn, adherence. To overcome these
      issues, three main technologies--polyethylene-glycol, Fc-neonatal IgG1 and
      albumin fusion products--have emerged into various stages of clinical
      development. Published data indicates an approximately 1.5- and fivefold increase
      in half-life of factor VIII and IX, respectively, compared to standard
      recombinant concentrates. Studies into efficacy and safety are starting to be
      published. Monitoring and optimal use of these new concentrates remains unknown.
      Weekly factor IX prophylaxis appears to be a feasible prophylactic regimen in
      haemophilia B patients. Weekly longer-acting FVIII is unlikely to provide
      adequate prophylaxis in most patients with haemophilia A but may reduce the
      frequency of infusions. Ongoing clinical trials and real life experience will
      help shape how these products can be used in practice and their cost
      effectiveness. The drive for convenience however should not overshadow the
      ultimate goal of prophylaxis, namely, preventing bleeding and arthropathy.

PMID- 25754017
TI  - Sclerosing mucoepidermoid carcinoma with eosinophilia of the thyroid: more
      aggressive than previously reported.
AB  - Sclerosing mucoepidermoid carcinoma with eosinophilia (SMECE) of the thyroid is a
      rare traditionally "low-grade" tumor that predominantly occurs in women.
      Approximately 50 cases have been reported in the literature. It arises in a
      background of Hashimoto thyroiditis and is characterized by nests of epidermoid
      and mucin-secreting cells located within an eosinophil-rich sclerotic stroma.
      Herein, we outline the clinicopathological and immunohistochemical
      characteristics of 6 cases of thyroid SMECE. All tumors were detected in women
      (age, 36-89 years; average, 59 years), and all patients underwent total
      thyroidectomies. Clinicopathological findings included extensive tumor invasion
      into the adjacent soft tissues, trachea, pharynx, and esophagus. Of 6 specimens,
      5 had positive surgical margins. Cervical lymph node metastases were seen in 4,
      and distant metastases were in 3 patients. Immunohistochemically, all tumors were
      positive for CK19, galectin 3, and p63 and negative for calcitonin, calponin, S
      100, and smooth muscle actin. Interestingly, 2 tumors also showed faint focal
      staining for thyroglobulin, and 2 others had focal positivity for thyroid
      transcription factor 1. Together, galectin 3 and CK19 expression supported the
      malignancy of these lesions, and p63 expression raised the possibility that these
      tumors originated from the ultimobranchial body. In summary, SMECE tumors in our
      series exhibit a clear female predominance with aggressive behavior and appear to
      arise from pluripotent solid cell nests. A correct diagnosis is crucial to
      providing SMECE patients with the appropriate treatment options, and we recommend
      a closer follow-up schedule than previously considered. 

PMID- 25754018
TI  - Novel X-ray imaging technology enables significant patient dose reduction in
      interventional cardiology while maintaining diagnostic image quality.
AB  - OBJECTIVES: The purpose of this study was to quantify the reduction in patient
      radiation dose during coronary angiography (CA) by a new X-ray technology, and to
      assess its impact on diagnostic image quality. BACKGROUND: Recently, a novel X
      ray imaging technology has become available for interventional cardiology, using
      advanced image processing and an optimized acquisition chain for radiation dose
      reduction. METHODS: 70 adult patients were randomly assigned to a reference X-ray
      system or the novel X-ray system. Patient demographics were registered and
      exposure parameters were recorded for each radiation event. Clinical image
      quality was assessed for both patient groups. RESULTS: With the same angiographic
      technique and a comparable patient population, the new imaging technology was
      associated with a 75% reduction in total kerma-area product (KAP) value (decrease
      from 47 Gycm2 to 12 Gycm2, P<0.001). Clinical image quality showed an equivalent
      detail and contrast for both imaging systems. On the other hand, the subjective
      appreciation of noise was more apparent in images of the new image processing
      system, acquired at lower doses, compared to the reference system. However, the
      higher noise content did not affect the overall image quality score, which was
      adequate for diagnosis in both systems. CONCLUSIONS: For the first time, we
      present a new X-ray imaging technology, combining advanced noise reduction
      algorithms and an optimized acquisition chain, which reduces patient radiation
      dose in CA drastically (75%), while maintaining diagnostic image quality. Use of
      this technology may further improve the radiation safety of cardiac angiography
      and interventions.

PMID- 25754019
TI  - Is it possible to have both standardised and person-centred care?

PMID- 25754020
TI  - Can individual home-based cognitive stimulation therapy benefit Parkinson's
      patients with mild to moderate cognitive impairment?

PMID- 25754022
TI  - Bridging the efficiency gap: fully bridged dinuclear Cu(I)-complexes for singlet
      harvesting in high-efficiency OLEDs.
AB  - The substitution of rare metals such as iridium and platinum in light-emitting
      materials is a key step to enable low-cost mass-production of organic light
      emitting diodes (OLEDs). Here, it is demonstrated that using a solution
      processed, fully bridged dinuclear Cu(I)-complex can yield very high
      efficiencies. An optimized device gives a maximum external quantum efficiency of
      23 +/- 1% (73 +/- 2 cd A(-1) ). 

PMID- 25754021
TI  - Protein kinase B and extracellular signal-regulated kinase contribute to the
      chondroprotective effect of morroniside on osteoarthritis chondrocytes.
AB  - Despite extensive studies on the multifaceted roles of morroniside, the main
      active constituent of iridoid glycoside from Corni Fructus, the effect of
      morroniside on osteoarthritis (OA) chondrocytes remains poorly understood. Here,
      we investigated the influence of morroniside on cultured human OA chondrocytes
      and a rat experimental model of OA. The results showed that morroniside enhanced
      the cell viability and the levels of proliferating cell nuclear antigen
      expression (PCNA), type II collagen and aggrecan in human OA chondrocytes,
      indicating that morroniside promoted chondrocyte survival and matrix synthesis.
      Furthermore, different doses of morroniside activated protein kinase B (AKT) and
      extracellular signal-regulated kinase (ERK) in human OA chondrocytes, and in
      turn, triggered AKT/S6 and ERK/P70S6K/S6 pathway, respectively. The PI3K/AKT
      inhibitor LY294002 or the MEK/ERK inhibitor U0126 attenuated the effect of
      morroniside on human OA chondrocytes, indicating that the activation of AKT and
      ERK contributed to the regulation of morroniside in human OA chondrocytes. In
      addition, the intra-articular injection of morroniside elevated the level of
      proteoglycans in cartilage matrix and the thickness of articular cartilage in a
      rat experimental model of OA, with the increase of AKT and ERK activation. As a
      consequence, morroniside has chondroprotective effect on OA chondrocytes, and may
      have the therapeutic potential for OA treatment. 

PMID- 25754023
TI  - Use of implanted gold fiducial markers with MV-CBCT image-guided IMRT for
      pancreatic tumours.
AB  - INTRODUCTION: Visualisation of soft tissues such as pancreatic tumours by mega
      voltage cone beam CT (MV-CBCT) is frequently difficult and daily localisation is
      often based on more easily seen adjacent bony anatomy. Fiducial markers implanted
      into pancreatic tumours serve as surrogates for tumour position and may more
      accurately represent absolute tumour position. Differences in daily shifts based
      on alignment to implanted fiducial markers vs. alignment to adjacent bony anatomy
      were compared. METHODS: Gold fiducial markers were placed into the pancreatic
      tumour under endoscopic ultrasound (EUS) guidance in 12 patients. Patients
      subsequently received image-guided intensity-modulated radiation therapy (IG
      IMRT). MV-CBCT was performed prior to each fraction and isocentre shifts were
      performed based on alignment to the fiducial markers. We retrospectively reviewed
      archived MV-CBCT datasets and calculated shift differences in the left-right
      (LR), superior-inferior (SI) and anterior-posterior (AP) axes relative to shifts
      based on alignment to adjacent bony anatomy. RESULTS: Two hundred forty-three
      fractions were analysed. The mean absolute difference in isocentre shifts between
      the fiducial markers and those aligned to bony anatomy was 3.4 mm (range 0-13
      mm), 6.3 mm (range 0-21 mm) and 2.6 mm (range 0-12 mm), in LR, SI and AP
      directions, respectively. The mean three-dimensional vector shift difference
      between markers vs. bony anatomy alignment was 8.6 mm. CONCLUSIONS: These data
      suggest that fiducial markers used in conjunction with MV-CBCT improve the
      accuracy of daily target delineation compared with localisation using adjacent
      bony anatomy and that gold fiducial markers using MV-CBCT alignment are a viable
      option for target localisation during IG-IMRT.

PMID- 25754024
TI  - Limb salvage in a partially amputated distal femur with extensive segmental bone
      loss using the nailing after lengthening technique: a case report.
AB  - Segmental long bone defects resulting from high-energy trauma with severe soft
      tissue loss are difficult problems to manage. Amputation was for a long time the
      primary mainstay of treatment. This is the report on a 15-year-old male patient
      who sustained a third-degree open, traumatic fracture with partial amputation of
      the left distal femur and extensive bone loss of 26 cm. Successful limb salvage
      was performed after vascular repair, shortening of the bone defect, primary
      placement of an antibiotic cement spacer and simple external fixation. This was
      followed by bifocal lengthening modifying the simple frame until limb equality
      was achieved and secondary intramedullary nailing 11 months after injury. 

PMID- 25754025
TI  - Targeting of the hydrophobic metabolome by pathogens.
AB  - The hydrophobic molecules of the metabolome - also named the lipidome -
      constitute a major part of the entire metabolome. Novel technologies show the
      existence of a staggering number of individual lipid species, the biological
      functions of which are, with the exception of only a few lipid species, unknown.
      Much can be learned from pathogens that have evolved to take advantage of the
      complexity of the lipidome to escape the immune system of the host organism and
      to allow their survival and replication. Different types of pathogens target
      different lipids as shown in interaction maps, allowing visualization of
      differences between different types of pathogens. Bacterial and viral pathogens
      target predominantly structural and signaling lipids to alter the cellular
      phenotype of the host cell. Fungal and parasitic pathogens have complex lipidomes
      themselves and target predominantly the release of polyunsaturated fatty acids
      from the host cell lipidome, resulting in the generation of eicosanoids by either
      the host cell or the pathogen. Thus, whereas viruses and bacteria induce
      predominantly alterations in lipid metabolites at the host cell level, eukaryotic
      pathogens focus on interference with lipid metabolites affecting systemic
      inflammatory reactions that are part of the immune system. A better understanding
      of the interplay between host-pathogen interactions will not only help elucidate
      the fundamental role of lipid species in cellular physiology, but will also aid
      in the generation of novel therapeutic drugs. 

PMID- 25754027
TI  - Treatment Outcome with Delayed Maxillary Obturator Prosthesis: Case Series of
      Four Patients.
AB  - A series of four patients is presented to indicate the possibility of success
      with delayed prosthodontic rehabilitation of acquired maxillary defects. Four
      patients with a history of hemi-maxillectomy in the past 3 to 5 years were
      rehabilitated with definitive obturator prostheses. All had partial maxillectomy
      on the right side. Because of delayed referral to the prosthodontic facility,
      immediate surgical and interim obturation was not planned. Definitive obturator
      prostheses were fabricated following the necessary steps and delivered to the
      patients. Prosthesis function was subsequently reassessed in these patients every
      fortnight for the first 3 months then once every quarter for the next 3 years,
      followed by once a year. Individual patient responses were evaluated at regular
      intervals. Components of prosthesis function assessed were esthetics, speech,
      mastication, and salivary control, all of which were restored to satisfactory
      levels by the definitive obturators. Thus, optimal restoration of esthetics and
      function is achievable despite a time lag in prosthodontic therapy after surgery.

PMID- 25754026
TI  - Meta-analyses of gene methylation and smoking behavior in non-small cell lung
      cancer patients.
AB  - Aberrant DNA methylation can be a potential genetic mechanism in non-small cell
      lung cancer (NSCLC). However, inconsistent findings existed among the recent
      association studies between cigarette smoking and gene methylation in lung
      cancer. The purpose of our meta-analysis was to evaluate the role of gene
      methylation in the smoking behavior of NSCLC patients. A total of 116 genes were
      obtained from 97 eligible publications in the current meta-analyses. Our results
      showed that 7 hypermethylated genes (including CDKN2A, RASSF1, MGMT, RARB, DAPK,
      WIF1 and FHIT) were significantly associated with the smoking behavior in NSCLC
      patients. The further population-based subgroup meta-analyses showed that the
      CDKN2A hypermethylation was significantly associated with cigarette smoking in
      Japanese, Chinese and Americans. In contrast, a significant association of RARB
      hypermethylation and smoking behavior was only detected in Chinese but not in
      Japanese. The genes with altered DNA methylation were likely to be potentially
      useful biomarkers in the early diagnosis of NSCLC. 

PMID- 25754028
TI  - End of life of patients treated with haemodialysis as narrated by their close
      relatives.
AB  - AIM: The study aimed to describe end of life for patients treated with
      maintenance haemodialysis as narrated by their close relatives. INTRODUCTION:
      Many patients undergoing haemodialysis are older, have several comorbidities and
      underestimated symptoms and are in their last year of life. To improve care, we
      need to know more about their end-of-life situation. DESIGN: Qualitative and
      descriptive. METHODS: Qualitative retrospective interviews were conducted with 14
      close relatives of deceased haemodialysis patients (3-13 months after death).
      Data were analysed using qualitative content analysis. The study is ethically
      approved. FINDINGS: In the last months, a gradual deterioration in health with
      acute episodes necessitating hospital admissions was described. This involved
      diminishing living space and expressions of dejection, but also of joy. Three
      patterns emerged in the last weeks: uncertain anticipation of death as life fades
      away; awaiting death after haemodialysis withdrawal; and sudden but not
      unexpected death following intensive care. Findings show complexities of
      decisions on haemodialysis withdrawal. CONCLUSIONS: Different end-of-life
      patterns all involved increasingly complex care needs and existential issues.
      Findings show a need for earlier care planning. The identification of
      organisational factors to facilitate continuity and whole person care to meet
      these patients' specific care needs with their complex symptom burdens and
      comorbidities is needed. Findings indicate the need for integration of a
      palliative care approach in the treatment of patients in haemodialysis care.

PMID- 25754029
TI  - Usefulness of specific anti-desmoglein 1 and 3 enzyme-linked immunoassay and
      indirect immunofluorescence in the evaluation of pemphigus activity.
AB  - OBJECTIVE: The objective was to assess the relationship between enzyme-linked
      immunoassay (ELISA) values of desmoglein (Dsg) 1 and Dsg3 antibodies and indirect
      immunofluorescence (IIF) values of anti-epithelial antibodies with disease
      activity in patients with pemphigus. PATIENTS AND METHODS: In a retrospective
      study, we analyzed 353 serum samples taken from 35 patients with pemphigus
      vulgaris (PV) and nine with pemphigus foliaceus (PF) during the course of the
      disease. In each sample, we measured anti-Dsg1 and anti-Dsg3 antibodies by ELISA.
      A receiver operating characteristics (ROC) curve was calculated to determine a
      cutoff value for anti-Dsg1 and anti-Dsg3 antibodies with optimal sensitivity and
      specificity. In 263 samples, we compared the ROC curves of anti-Dsg1 and anti
      Dsg3 antibodies with the ROC curves of the IIF results. RESULTS: Activity of
      pemphigus was associated with a wide range of anti-Dsg1 and anti-Dsg3 antibody
      values. Levels of anti-Dsg1 antibodies showed a better relationship with
      cutaneous activity of pemphigus than levels of IIF anti-epithelial antibodies.
      The levels of IIF anti-epithelial antibodies showed a relationship with activity
      of mucosas similar to the levels of anti-Dsg3 antibodies. DISCUSSION: Abnormal
      values of anti-Dsg antibodies are not always associated with disease activity.
      ELISA detects both pathogenic and nonpathogenic anti-Dsg antibodies. CONCLUSIONS:
      Therapeutic strategies should not be based exclusively on anti-Dsg antibody
      values. Anti-Dsg1 antibodies showed a closer relationship with skin activity than
      IIF, while anti-Dsg3 antibodies showed a relationship with mucosal activity
      similar to the IIF test.

PMID- 25754032
TI  - A new case of bacterial endocarditis in a child with severe Haemophilia A
      carrying a central venous access device.

PMID- 25754031
TI  - The exonuclease Nibbler regulates age-associated traits and modulates piRNA
      length in Drosophila.
AB  - Nibbler (Nbr) is a 3'-to-5' exonuclease that trims the 3'end of microRNAs
      (miRNAs) to generate different length patterns of miRNAs in Drosophila. Despite
      its effect on miRNAs, we lack knowledge of its biological significance and
      whether Nbr affects other classes of small RNAs such as piRNAs and endo-siRNAs.
      Here, we characterized the in vivo function of nbr by defining the Nbr protein
      expression pattern and loss-of-function effects. Nbr protein is enriched in the
      ovary and head. Analysis of nbr null animals reveals adult-stage defects that
      progress with age, including held-up wings, decreased locomotion, and brain
      vacuoles, indicative of accelerated age-associated processes upon nbr loss.
      Importantly, these effects depend on catalytic residues in the Nbr exonuclease
      domain, indicating that the catalytic activity is responsible for these effects.
      Given the impact of nbr on miRNAs, we also analyzed the effect of nbr on piRNA
      and endo-siRNA lengths by deep-sequence analysis of libraries from ovaries. As
      with miRNAs, nbr mutation led to longer length piRNAs - an effect that was
      dependent on the catalytic residues of the exonuclease domain. These analyses
      indicate a role of nbr on age-associated processes and to modulate length of
      multiple classes of small RNAs including miRNAs and piRNAs in Drosophila.

PMID- 25754030
TI  - Phosphoinositide regulation of TRPV1 revisited.
AB  - The heat- and capsaicin-sensitive transient receptor potential vanilloid 1 ion
      channel (TRPV1) is regulated by plasma membrane phosphoinositides. The effects of
      these lipids on this channel have been controversial. Recent articles re-ignited
      the debate and also offered resolution to place some of the data in a coherent
      picture. This review summarizes the literature on this topic and provides a
      detailed and critical discussion on the experimental evidence for the various
      effects of phosphatidylinositol 4,5-bisphosphayte [PI(4,5)P2 or PIP2] on TRPV1.
      We conclude that PI(4,5)P2 and potentially its precursor PI(4)P are positive
      cofactors for TRPV1, acting via direct interaction with the channel, and their
      depletion by Ca(2+)-induced activation of phospholipase Cdelta isoforms
      (PLCdelta) limits channel activity during capsaicin-induced desensitization.
      Other negatively charged lipids at higher concentrations can also support channel
      activity, which may explain some controversies in the literature. PI(4,5)P2 also
      partially inhibits channel activity in some experimental settings, and relief
      from this inhibition upon PLCbeta activation may contribute to sensitization. The
      negative effect of PI(4,5)P2 is more controversial and its mechanism is less well
      understood. Other TRP channels from the TRPV and TRPC families may also undergo
      similar dual regulation by phosphoinositides, thus the complexity of TRPV1
      regulation is not unique to this channel. 

PMID- 25754034
TI  - A thermodynamic and theoretical view for enzyme regulation.
AB  - Precise regulation is fundamental to the proper functioning of enzymes in a cell.
      Current opinions about this, such as allosteric regulation and dynamic
      contribution to enzyme regulation, are experimental models and substantially
      empirical. Here we proposed a theoretical and thermodynamic model of enzyme
      regulation. The main idea is that enzyme regulation is processed via the
      regulation of abundance of active conformation in the reaction buffer. The
      theoretical foundation, experimental evidence, and experimental criteria to test
      our model are discussed and reviewed. We conclude that basic principles of enzyme
      regulation are laws of protein thermodynamics and it can be analyzed using the
      concept of distribution curve of active conformations of enzymes. 

PMID- 25754033
TI  - Methylselenocysteine preventing castration-resistant progression of prostate
      cancer.
AB  - BACKGROUND: Castration-resistant progression of prostate cancer after androgen
      deprivation therapy remains a critical challenge in the clinical management of
      prostate cancer. Resurgent androgen receptor activity is an established driver of
      castration-resistant progression, and upregulation of androgen receptor
      expression has been implicated to contribute to the resurgent androgen receptor
      activity. We reported previously that methylselenocysteine can decrease the
      expression and activity of androgen receptor. Here we investigated the ability of
      methylselenocysteine to inhibit castration-resistant progression of prostate
      cancer. METHODS: The regrowth of LNCaP prostate cancer xenografts after
      castration was monitored. The levels of prostate-specific antigen in mouse serum
      were measured by ELISA. Tumor cell proliferation and apoptosis were analyzed via
      Ki-67 immunohistochemistry and TUNEL assay, respectively. Intratumoral
      angiogenesis was assessed by immunohistochemistry staining of vascular
      endothelial growth factor and CD31. RESULTS: We showed that methylselenocysteine
      delayed castration-resistant regrowth of LNCaP xenograft tumors after androgen
      deprivation. This was accompanied by decreased serum levels of prostate-specific
      antigen, inhibition of prostate cancer cell proliferation and tumor angiogenesis,
      as well as downregulation of androgen receptor and induction of apoptosis in the
      relapsed tumors. CONCLUSIONS: The present study represents the first to show the
      preclinical efficacy of methylselenocysteine in delaying castration-resistant
      progression of prostate cancer. The findings provide a rationale for evaluating
      the clinical application of combining methylselenocysteine with androgen
      deprivation therapy for the treatment of advanced prostate cancer.

PMID- 25754035
TI  - Vitamin D -- the sun hormone. Life in environmental mismatch.
AB  - While some representatives of the animal kingdom were improving their biological
      mechanisms and properties for adapting to ever-changing life conditions, the
      genus Homo was developing backward: human individuals were losing their
      adaptation to life areas conquered earlier. Losing step-by-step their useful
      traits including the body hair cover, the primitive genus Homo retained his
      viability only under very favorable conditions of the equatorial Africa.
      Protection from UV radiation danger was provided only by pigmentation of skin,
      hair, and eyes. However, "impoverished" individuals of this genus gained the
      ability to walk upright. Their hands became free from participation in movement
      and became fine tools for producing useful instruments, from the stone knife to
      the computer. The major consequence of upright movement and hand development
      became the powerful development of the brain. A modern human, Homo sapiens,
      appeared capable of conquering very diverse new habitats. The human's expansion
      on the Earth occurred somewhat limited by his dependence on vitamin D. His
      expansion into new areas with lower Sun activity was partially associated with
      the loss of skin pigmentation. But there is an open question, whether under these
      new conditions he is satisfactorily provided with vitamin D. This paper discusses
      the following problems: how can we ensure a sufficient intake of vitamin D, how
      much does an individual require for his existence and optimal life, what will be
      consequences of vitamin D deficiency, and what are the prospects for better
      provision with vitamin D? 

PMID- 25754036
TI  - Human myeloma immunoglobulins of the fourth subclass (IgG4 MAM) contain a
      fraction with different properties of CH2 domains.
AB  - A long-lived metastable minor fraction has been detected and characterized in
      myeloma protein IgG4 MAM by hydro- and thermodynamic methods. The sedimentation
      constants of the minor and the major protein fractions are different. The
      stability of the two CH2 domains in the minor fraction varies. The unique
      characteristics of these IgG4 MAM conformers arise from the fact that on exchange
      of the heavy chains between IgG4 molecules, in some of them only one noncanonical
      bond Cys226-Cys229 is formed in the central part of the "hinge region" instead of
      two canonical interchain disulfide bonds Cys226-Cys226 and Cys229-Cys229. This
      leads to asymmetric structure of the IgG4 MAM molecules. 

PMID- 25754037
TI  - Role of loop L5-6 connecting transmembrane segments M5 and M6 in biogenesis and
      functioning of yeast Pma1 H+-ATPase.
AB  - The L5-6 loop is a short extracytoplasmic stretch (714-DNSLDID) connecting
      transmembrane segments M5 and M6 and forming along with segments M4 and M8 the
      core through which cations are transported by H+-, Ca2+-, K+,Na+-, H+,K+-, and
      other P2-ATPases. To study structure-function relationships within this loop of
      the yeast plasma membrane Pma1 H+-ATPase, alanine- and cysteine-scanning
      mutagenesis has been employed. Ala and Cys substitutions for the most conserved
      residue (Leu717) led to complete block in biogenesis preventing the enzyme from
      reaching secretory vesicles. The Ala replacement at Asp714 led to five-fold
      decrease in the mutant expression and loss of its activity, while the Cys
      substitution blocked biogenesis completely. Replacements of other residues did
      not lead to loss of enzymatic activity. Additional replacements were made for
      Asp714 and Asp720 (Asp(r)Asn/Glu). Of the substitutions made at Asp714, only
      D714N partially restored the mutant enzyme biogenesis and functioning. However,
      all mutant enzymes with substituted Asp720 were active. The expressed mutants (34
      95% of the wild-type level) showed activity high enough (35-108%) to be analyzed
      in detail. One of the mutants (I719A) had three-fold reduced coupling ratio
      between ATP hydrolysis and H+ transport; however, the I719C mutation was rather
      indistinguishable from the wild-type enzyme. Thus, substitutions at two of the
      seven positions seriously affected biogenesis and/or functioning of the enzyme.
      Taken together, these results suggest that the M5-M6 loop residues play an
      important role in protein stability and function, and they are probably
      responsible for proper arrangement of transmembrane segments M5 and M6 and other
      domains of the enzyme. This might also be important for the regulation of the
      enzyme. 

PMID- 25754038
TI  - Nonhydrolyzable ATP analog 5'-adenylyl-imidodiphosphate (AMP-PNP) does not
      inhibit ATP-dependent scanning of leader sequence of mRNA.
AB  - The objective of the present work was to determine whether it is possible to use
      a nonhydrolyzable analog of ATP (AMP-PNP) as an inhibitor of ATP-dependent
      scanning of the leader sequence of eukaryotic mRNA in translation initiation-.
      The formation of ribosomal 48S initiation complexes at the start codon of the
      capped mRNA leader sequence of rabbit beta-globin mRNA was studied. The study was
      carried out in a system composed of individual components of translation
      initiation. The dependences of the efficiency of formation of 48S initiation
      complexes on ATP concentration and incubation time were obtained in the absence
      and presence of AMP-PNP. It was found that AMP-PNP did not affect the efficiency
      of formation of 48S initiation complexes in all cases under study. We conclude
      that the uncleavable analog of ATP, AMP-PNP, is not an inhibitor of translation
      initiation in eukaryotes. 

PMID- 25754039
TI  - Photosystem activity and state transitions of the photosynthetic apparatus in
      cyanobacterium Synechocystis PCC 6803 mutants with different redox state of the
      plastoquinone pool.
AB  - To better understand how photosystem (PS) activity is regulated during state
      transitions in cyanobacteria, we studied photosynthetic parameters of photosystem
      II (PSII) and photosystem I (PSI) in Synechocystis PCC 6803 wild type (WT) and
      its mutants deficient in oxidases (Ox(-)) or succinate dehydrogenase (SDH(-)).
      Dark-adapted Ox(-) mutant, lacking the oxidation agents, is expected to have a
      reduced PQ pool, while in SDH(-) mutant the PQ pool after dark adaptation will be
      more oxidized due to partial inhibition of the respiratory chain electron
      carriers. In this work, we tested the hypothesis that control of balance between
      linear and cyclic electron transport by the redox state of the PQ pool will
      affect PSII photosynthetic activity during state transition. We found that the PQ
      pool was reduced in Ox(-) mutant, but oxidized in SDH(-) mutant after prolonged
      dark adaptation, indicating different states of the photosynthetic apparatus in
      these mutants. Analysis of variable fluorescence and 77K fluorescence spectra
      revealed that the WT and SDH(-) mutant were in State 1 after dark adaptation,
      while the Ox(-) mutant was in State 2. State 2 was characterized by ~1.5 time
      lower photochemical activity of PSII, as well as high rate of P700 reduction and
      the low level of P700 oxidation, indicating high activity of cyclic electron
      transfer around PSI. Illumination with continuous light 1 (440 nm) along with
      flashes of light 2 (620 nm) allowed oxidation of the PQ pool in the Ox(-) mutant,
      thus promoting it to State 1, but it did not affect PSII activity in dark adapted
      WT and SDH(-) mutant. State 1 in the Ox(-) mutant was characterized by high
      variable fluorescence and P700(+) levels typical for WT and the SDH(-) mutant,
      indicating acceleration of linear electron transport. Thus, we show that PSII of
      cyanobacteria has a higher photosynthetic activity in State 1, while it is
      partially inactivated in State 2. This process is controlled by the redox state
      of PQ in cyanobacteria through enhancement/inhibition of electron transport on
      the acceptor side of PSII. 

PMID- 25754040
TI  - Effect of trehalose on oxygen evolution and electron transfer in photosystem 2
      complexes.
AB  - The pigment-protein complex of photosystem 2 (PS 2) catalyzes the light-driven
      oxidation of water molecule and the reduction of plastoquinone. In this work, we
      studied the effect of the disaccharide trehalose, which is unique in its
      physicochemical properties, on isolated PS 2 complex. It was found that trehalose
      significantly stimulated the steady-state rate of oxygen evolution. The study of
      single flash-induced fluorescence decay kinetics demonstrated that trehalose did
      not affect the rate of QA(-) oxidation, although it led to an increase in the
      relative fractions of PS 2 reaction centers capable of QA(-) oxidation. Trehalose
      also prevented PS 2 complexes from being inactivated on prolonged storage. We
      propose that in the presence of trehalose, which affects the extent of hydration,
      the protein can preferentially exist in a more optimal conformation for effective
      functioning. 

PMID- 25754041
TI  - Attempt to optimize some properties of fluorescent chimeras of human small heat
      shock protein HspB1 by modifying linker length and nature.
AB  - Chimerical proteins consisting of enhanced yellow fluorescent protein (EYFP)
      connected by linkers of different length and nature to the N-terminal end of
      small heat shock protein HspB1 were obtained and characterized. To obtain
      fluorescent chimeras with properties similar to those of unmodified small heat
      shock protein, we used either 12-residue-long linkers of different nature (highly
      flexible Gly-Ser linker (L1), rigid alpha-helical linker (L2), or rigid Pro-Ala
      linker (L3)) or highly flexible Gly-Ser linker consisting of 12, 18, or 21
      residues. The wild-type HspB1 formed large stable oligomers consisting of more
      than 20 subunits. Independent of the length or the nature of the linker, all the
      fluorescent chimeras formed small (5-9 subunits) oligomers tending to dissociate
      at low protein concentration. Chaperone-like activity of the wild-type HspB1 and
      its fluorescent chimeras were compared using lysozyme as a model protein
      substrate. Under the conditions used, all the fluorescent chimeras possessed
      higher chaperone-like activity than the wild-type HspB1. Chaperone-like activity
      of fluorescent chimeras with L1 and L3 linkers was less different from that of
      the wild-type HspB1 compare to the chaperone-like activity of chimeras with rigid
      L2 linker. Increase in the length of L1 linker from 12 up to 21 residues leads to
      decrease in the difference in the chaperone-like activity between the wild-type
      protein and its fluorescent chimeras. Since the N-terminal domain of small heat
      shock proteins participates in formation of large oligomers, any way of
      attachment of fluorescent protein to the N-terminal end of HspB1 leads to
      dramatic changes in its oligomeric structure. Long flexible linkers should be
      used to obtain fluorescent chimeras with chaperone-like properties similar to
      those of the wild-type HspB1. 

PMID- 25754042
TI  - Quantitative analysis of structure-activity relationships of tetrahydro-2H
      isoindole cyclooxygenase-2 inhibitors.
AB  - Using the GUSAR program, structure-activity relationships on inhibition of
      cyclooxygenase-2 (COX-2) catalytic activity were quantitatively analyzed for
      twenty-six derivatives of 4,5,6,7-tetrahydro-2H-isoindole, 2,3-dihydro-1H
      pyrrolyzine, and benzothiophene in the concentration range of 0.6-700 nmol/liter
      IC50 values. Six statistically significant consensus QSAR models for prediction
      of IC50 values were designed based on MNA- and QNA-descriptors and their
      combinations. These models demonstrated high accuracy in the prediction of IC50
      values for structures of both training and test sets. Structural fragments of the
      COX-2 inhibitors capable of strengthening or weakening the desired property were
      determined using the same program. This information can be taken into
      consideration on molecular design of new COX-2 inhibitors. It was shown that in
      most cases, the influence of structural fragments on the inhibitory activity of
      the studied compounds revealed with the GUSAR program coincided with the results
      of expert evaluation of their effects based on known experimental data, and this
      can be used for optimization of structures to change the value of their
      biological activity. 

PMID- 25754043
TI  - Effect of insulin, the glutathione system, and superoxide anion radical in
      modulation of lipolysis in adipocytes of rats with experimental diabetes.
AB  - Spontaneous lipolysis was found to be increased in adipocytes of rats with
      alloxan-induced diabetes. In addition, isoproterenol-stimulated hydrolysis of
      triacylglycerols was inhibited against the background of oxidative stress and
      decreased redox-status of cells. A decrease in the ability of insulin to inhibit
      isoproterenol-stimulated lipolysis in adipocytes that were isolated from adipose
      tissue of rats with experimental diabetes was found, which shows a disorder in
      regulation of lipolysis in adipocytes by the hormone in alloxan-induced diabetes.
      Based on these findings, we concluded that there is an influence of reactive
      oxygen species, superoxide anion radical in particular, and redox potential of
      the glutathione system on molecular mechanisms of change in lipolysis intensity
      in rat adipocytes in alloxan-induced oxidative stress. Activation of spontaneous
      lipolysis under conditions of oxidative stress might be a reason for the high
      concentration of free fatty acids in blood plasma in experimental diabetes, and
      this may play a significant role in development of insulin resistance and
      appearance of complications of diabetes. 

PMID- 25754044
TI  - Implication of alpha2beta1 integrin in anoikis of MCF-7 human breast carcinoma
      cells.
AB  - Silencing of alpha2beta1 integrin expression significantly promoted anchorage
      dependent apoptosis (anoikis) and drastically reduced clonal activity of MCF-7
      human breast carcinoma cells. Depletion of alpha2beta1 enhanced the production of
      apoptotic protein p53 and of inhibitor of cyclin-dependent protein kinases, p27,
      while downregulating antiapoptotic protein Bcl-2 and multifunctional protein
      cMyc. Blocking the expression of alpha2beta1 had no effect on activity of protein
      kinase Akt, but it sharply increased the kinase activity of Erk1/2.
      Pharmacological inhibition of Erk1/2 had a minor effect on anoikis of control
      cells, while it reduced anoikis of cells with downregulated alpha2beta1 to the
      level of control cells. The data show for the first time that integrin
      alpha2beta1 is implicated in the protection of tumor cells from anoikis through a
      mechanism based on the inhibition of protein kinase Erk. 

PMID- 25754045
TI  - Effects of inhibitors of key enzymes of sphingolipid metabolism on insulin
      induced glucose uptake and glycogen synthesis in liver cells of old rats.
AB  - Sphingolipids play an important role in the development of insulin resistance.
      Ceramides are the most potent inhibitors of insulin signal transduction.
      Ceramides are generated in response to stress stimuli and in old age. In this
      work, we studied the possible contribution of different pathways of sphingolipid
      metabolism in age-dependent insulin resistance development in liver cells.
      Inhibition of key enzymes of sphingolipid synthesis (serine palmitoyl
      transferase, ceramide synthase) and degradation (neutral and acidic SMases) by
      means of specific inhibitors (myriocin, fumonisin B1, imipramine, and GW4869) was
      followed with the reduction of ceramide level and partly improved insulin
      regulation of glucose metabolism in "old" hepatocytes. Imipramine and GW4869
      decreased significantly the acidic and neutral SMase activities, respectively.
      Treatment of "old" cells with myriocin or fumonisin B1 reduced the elevated in
      old age ceramide and SM synthesis. Ceramide and SM levels and glucose metabolism
      regulation by insulin could be improved with concerted action of all tested
      inhibitors of sphingolipid turnover on hepatocytes. The data demonstrate that not
      only newly synthesized ceramide and SM but also neutral and acidic SMase
      dependent ceramide accumulation plays an important role in development of age
      dependent insulin resistance. 

PMID- 25754046
TI  - PEG-chitosan and glycol-chitosan for improvement of biopharmaceutical properties
      of recombinant L-asparaginase from Erwinia carotovora.
AB  - Conjugation with the new branched copolymers, PEG-chitosan and glycol-chitosan,
      is suggested to improve the therapeutic properties of L-asparaginase from Erwinia
      carotovora (EwA). The structure and composition of such conjugates were optimized
      for maximal catalytic efficiency (kcat/KM) under physiological conditions,
      yielding improvement by a factor of 3-6 compared to the native enzyme. This
      effect is attributed mainly to the shift of pH activity profile towards lower pH
      values due to the polycationic nature of the copolymer. The thermostability of
      EwA conjugates was also considerably improved. Chito-PEGylation, similarly to
      PEGylation, can be expected to improve pharmacokinetic properties and to reduce
      immunogenicity of this medically relevant enzyme. It is worth mentioning that a
      new versatile approach based on IR spectroscopy has been developed to determine
      PEG-chitosan copolymer composition as well as composition of copolymer-enzyme
      conjugates. The proposed analytic method is "reagent-free" and allows fast and
      reliable determination of parameters of interest from the single IR spectrum in
      contrast to laborious and unreliable methods based on polymer free amino group
      titration with TNBS and OPA. 

PMID- 25754047
TI  - The A2B adenosine receptor colocalizes with adenosine deaminase in resting
      parietal cells from gastric mucosa.
AB  - The A2B adenosine receptor (A2BR) mediates biological responses to extracellular
      adenosine in a wide variety of cell types. Adenosine deaminase (ADA) can degrade
      adenosine and bind extracellularly to adenosine receptors. Adenosine modulates
      chloride secretion in gastric glands and gastric mucosa parietal cells. A close
      functional link between surface A2BR and ADA has been found on cells of the
      immune system, but whether this occurs in the gastrointestinal tract is unknown.
      The goal of this study was to determine whether A2BR and ADA are coexpressed at
      the plasma membrane of the acid-secreting gastric mucosa parietal cells. We used
      isolated gastric parietal cells after purification by centrifugal elutriation.
      The membrane fraction was obtained by sucrose gradient centrifugation. A2BR mRNA
      expression was analyzed by RT-PCR. The surface expression of A2BR and ADA
      proteins was evaluated by Western blotting, flow cytometry and confocal
      microscopy. Our findings demonstrate that A2BR and ADA are expressed in cell
      membranes isolated from gastric parietal cells. They show a high degree of
      colocalization that is particularly evident in the surface of contact between
      parietal cells. The confocal microscopy data together with flow cytometry
      analysis suggest a tight association between A2BR and ADA that might be
      specifically linked to glandular secretory function. 

PMID- 25754048
TI  - Enhanced transformation of tetrabromobisphenol a by nitrifiers in nitrifying
      activated sludge.
AB  - The fate of the most commonly used brominated flame retardant,
      tetrabromobisphenol A (TBBPA), in wastewater treatment plants is obscure. Using a
      (14)C-tracer, we studied TBBPA transformation in nitrifying activated sludge
      (NAS). During the 31-day incubation, TBBPA transformation (half-life 10.3 days)
      was accompanied by mineralization (17% of initial TBBPA). Twelve metabolites,
      including those with single benzene ring, O-methyl TBBPA ether, and nitro
      compounds, were identified. When allylthiourea was added to the sludge to
      completely inhibit nitrification, TBBPA transformation was significantly reduced
      (half-life 28.9 days), formation of the polar and single-ring metabolites
      stopped, but O-methylation was not significantly affected. Abiotic experiments
      confirmed the generation of mono- and dinitro-brominated forms of bisphenol A in
      NAS by the abiotic nitration of TBBPA by nitrite, a product of ammonia-oxidizing
      microorganisms (AOMs). Three biotic (type II ipso-substitution, oxidative
      skeletal cleavage, and O-methylation) and one abiotic (nitro-debromination)
      pathways were proposed for TBBPA transformation in NAS. Apart from O-methylation,
      AOMs were involved in three other pathways. Our results are the first to provide
      information about the complex metabolism of TBBPA in NAS, and they are consistent
      with a determining role for nitrifiers in TBBPA degradation by initiating its
      cleavage into single-ring metabolites that are substrates for the growth of
      heterotrophic bacteria. 

PMID- 25754049
TI  - The IGRA tests: where are we now?

PMID- 25754050
TI  - Lung cancer: our blood, sweat and fears.

PMID- 25754051
TI  - Occurrence of alert pathogens in patients hospitalised in the department of lung
      diseases.
AB  - INTRODUCTION: Infections caused by multiple drug-resistant pathogens represent an
      increasingly often encountered challenge in clinical practice. The problem
      particularly applies to patients with chronic lung diseases resulting in multiple
      hospitalisations. The aim of this paper was to analyse the incidence of alert
      pathogens isolated from patients hospitalised in the department of lung diseases,
      who were divided into three groups: patients qualified for lung transplantation,
      patients treated for neoplastic diseases and patients with chronic lung diseases.
      MATERIALS AND METHODS: Analysis involved microbiological test results of 3950
      samples obtained from 3521 patients divided into: 200 patients being qualified
      for lung transplantation, 1292 patients treated for neoplastic diseases and 2029
      patients with chronic lung diseases. RESULTS: Infection with alert pathogen was
      found in 155 of 3521 patients (4.4%). Most often isolated infectious agent was P.
      aeruginosa, which accounted for 27% of infections. Other pathogens were as
      follows A. baumanii ESBL(-) (13%), S. pneumoniae (12%), E. cloacae ESBL(+) (10%),
      K. pneumoniae ESBL(+) (10%), S. aureus MRSA (8%), E. faecalis (7%), E. coli
      ESBL(+) (6%), S. maltophilia ESBL(+) (5%) and E. kobei ESBL(+) (2%). Alert
      pathogens were found in 31 (15%) of 200 patients being qualified for lung
      transplantation, 89 (4.4%) of 2029 patients with chronic lung diseases and 35
      (2.7%) of 1292 patients treated for neoplastic diseases. Difference between
      infection frequency in patients being qualified for lung transplantation and the
      remaining groups was statistically significant (p < 0.01). P. aeruginosa
      infection was the most frequent in all groups. It constituted 35% in patients
      being qualified for lung transplantation, 29% in patients treated for neoplastic
      diseases and 22% in patients with chronic lung diseases. CONCLUSIONS: Infections
      caused by alert pathogens were found in more than 4% of patients hospitalised in
      the department of lung diseases between 2007 and 2011. Their frequency was
      significantly higher in patients being qualified for lung transplantation than in
      other analysed groups. In all examined groups the most frequently isolated
      bacteria was P. aeruginosa (27% of all isolates).

PMID- 25754052
TI  - Lung cancer in Podkarpackie region in the years 2002-2011.
AB  - INTRODUCTION: Lung cancer is one of the greatest challenges for modern medicine
      and in Poland the incidence and mortality rate are one of the highest. The aim of
      the study was to assess trends in the incidence and mortality rate lung cancer in
      the Podkarpackie province in the years 2002-2011. MATERIAL AND METHODS: 9993
      cases (8018 men and 1975 women) and 8782 deaths (7211 men and 1571 women) of lung
      cancer were analyzed. Crude rate and standardized coefficients of incidence and
      mortality as well as stratum weight, and cumulative risk of incidence and
      mortality were calculated. RESULTS: In 2011, in Podkarpackie province a decrease
      number of lung cancer cases in men was observed compared to 2002 amounting to 195
      case, but in women, an increase of 39 new cases was noted. Incidence rates in men
      were in the range of 65.8-93.1/100,000, while in women they ranged 9.6
      35.2/100,000. Mortality rates for males ranged from 59.2 to 82.8/100,000, and in
      women from 6.1 to 29.0/100,000. Considerable diversity in incidence and mortality
      in different districts of the province of Podkarpackie was observed. CONCLUSIONS:
      In the years 2002-2011 the values of incidence and mortality rates for men in
      Podkarpackie province were lower than the rates for Poland, in case of women the
      same rates for Podkarpackie were almost two times lower than the rates for
      Poland. In the years 2002-2011 the highest value of incidence and mortality rate
      out of all districts of Podkarpackie Province was observed in the district
      Lubaczow for men and in Przemysl in case of women.

PMID- 25754053
TI  - Correlation between hyperinflation defined as an elevated RV/TLC ratio and body
      composition and cytokine profile in patients with chronic obstructive pulmonary
      disease.
AB  - INTRODUCTION: Body composition is an important prognostic factor in patients with
      COPD. The decrease in fat free mass (FFM), muscle mass (MM) and increase in
      visceral fat is associated with an elevated secretion of cytokines which promote
      systemic inflammation. The aim of the study was to evaluate body composition and
      the cytokine profile in patients with COPD in relation with the presence of
      hyperinflation. MATERIAL AND METHODS: The study group consisted of 149 patients
      (61F, 88M) with stable COPD in all stages of severity aged 68 +/- 8.8 yrs. All
      the patients underwent spirometry and bodypletysmography with bronchial
      reversibility testing. Hyperinflation was defined as RV%TLC > 48% and > 126%
      predicted. Body composition was analyzed by bioimpedance. The following serum
      inflammatory markers were evaluated: C-reactive protein, IL-6, IL-8, TNF-a, CC16,
      adiponectin and resistin. RESULTS: Hyperinflation was found in 96 patients (group
      A) and it was more frequent in women than men (49/61 vs. 47/88, p < 0.001). BMI
      and age in this group were comparable to those in patients without hyperinflation
      (group B). Patients with hyperinflation have lover FFM, FFM index, MM and MM
      index and total body water and higher fat mass and fat mass index. We found
      significantly higher serum concentrations of inflammatory markers in group A: IL
      6 - 6.4 +/- 10.9 vs. 3.6 +/- 4.2 pg/ml, resistin - 9.3 +/- 4.2 vs. 7.6 +/- 2.4
      ng/ml, CRP 4.1 +/- 2.3 vs. 2.9+/-2.1 mg/l, respectively. CONCLUSIONS: Patients
      with hyperinflation have a lower FFMI, TBW and MMI and a higher proportion of fat
      tissue. Hyperinflation is associated with elevated concentrations of inflammatory
      markers what may be associated with more severe disease. Body compositions
      abnormality and higher activity of systemic inflammation could therefore be a
      negative prognostic factor in COPD patients.

PMID- 25754054
TI  - Interferon gamma release assays based on M. tuberculosis-specific antigens in
      sarcoidosis patients.
AB  - INTRODUCTION: This study is a part of the project on interferon gamma release
      assays performed in the group of untreated sarcoidosis patients formerly BCG
      vaccinated. The aim of the study was to assess the rate of positive commercial
      interferon g release assays in sarcoidosis patients. We discussed the results in
      the context of hypothesis that M. tuberculosis antigens may play a role in the
      pathogenesis of sarcoidosis. MATERIAL AND METHODS: 151 patients, mean age 38 +/-
      10.3, treatment naive, with newly diagnosed pulmonary sarcoidosis were enrolled
      into the study. All participants underwent QFT-GIT assay. A subgroup of 81
      patients underwent also T-SPOT.TB assay. RESULTS: QFT-GIT was positive in 7/151.
      T-SPOT.TB was positive in 3/81. There were no indeterminate results in both
      IGRAs. There was no statistically significant relationship between IGRAs results
      and sarcoidosis parameters such as the radiologic stage, disease duration and the
      presence of Lofgren's syndrome. CONCLUSIONS: In sarcoidosis patients formerly BCG
      vaccinated, positive rate of IGRAs was 4.6% for QFT-GIT and 3.7% for T-SPOT. TB.
      We did not find the influence of the selected parameters of sarcoidosis on IGRAs
      results.

PMID- 25754055
TI  - Tracheobronchopathia osteochondroplastica-case report and literature review.
AB  - Tracheobronchopathia osteochondroplastica (TBO) is a rare disease of unknown
      etiology characterised by a formation of multiple, cartilaginous and
      osteocartilaginous submucosal nodules in the trachea and major bronchi. The
      course of the disease is usually benign but the narrowing of the respiratory
      tract can lead to chronic non-specific clinical symptoms. We present a case of a
      50-year old man with chronic exertional dyspnoea and stenosis of the trachea
      visible in imaging tests, in whom the symptoms were caused by TBO. 

PMID- 25754056
TI  - "Saw-tooth sign" in upper airway disorders-a case report.
AB  - Spirometry flow-volume loop measurement is the screening test of choice to rule
      out obstructive lung diseases. Flow oscillations occasionally seen on flow volume
      loops, referred to as a "saw-tooth" sign, are thought to be due to an upper
      airway obstructive processes associated with upper airway collapsibility. Widely
      described in obstructive sleep apnea syndrome, flow oscillations have also been
      linked to many other upper airway pathologies. The mechanism by which flow
      oscillations occur is centered on the inspiratory and expiratory flow of air. It
      has been theorized that the mechanism of flow oscillations result from rapid
      intermittent changes in driving pressure or airway resistance. Since visual
      inspection of the flow volume loop can reveal presence of flow oscillations
      clinicians should be aware of this phenomenon and the presence of flow loop
      oscillations should clue physicians to rule out upper airway pathology. 

PMID- 25754057
TI  - Allergic bronchopulmonary aspergillosis presenting as lobar or total lung
      collapse.
AB  - INTRODUCTION: Allergic bronchopulmonary aspergillosis (ABPA) is a T-helper cell 2
      (Th2) mediated hypersensitive lung disorder in response to Aspergillus that
      usually affects asthmatic and cystic fibrosis (CF) patients. ABPA rarely presents
      as lung collapse and such kind of presentation is very rare in non asthmatic
      patients. We are presenting a series of three cases in which ABPA presented as
      lobar or total lung collapse. ABPA presenting as opaque hemithorax is a rarity
      with only a few of them reported in the literature. CASE SERIES: the first case
      described is a 45-year non-smoker with history suggestive of bronchial asthma and
      on chest radiological examination was found to have opaque right hemithorax. The
      second case is of 62-year non-smoker non-asthmatic patient who presented to us as
      left lung collapse. The last case is of middle lobe collapse in asthmatic male.
      All cases ultimately were proved to be having ABPA and after treatment showed
      marked clinical and radiological improvement. CONCLUSIONS: The present case
      series highlights the need for aggressive approach in diagnosing this treatable
      condition in cases presenting as segmental or total lung collapse. The condition
      has a good prognosis if detected early.

PMID- 25754058
TI  - Pulmonary artery stenosis due to embryonal carcinoma with primary mediastinal
      location.
AB  - A 29-year old man was admitted to the intensive care unit after losing
      consciousness. On physical examination, a loud systolic murmur over the heart was
      found. Echocardiography revealed narrowing of pulmonary artery with high pressure
      gradient. Computed tomography of the chest revealed the presence of large tumour
      localised in the upper anterior mediastinum. Due to the risk of total closure of
      the pulmonary artery, interventional mediastinotomy was performed and diagnosis
      of carcinoma embryonale was established. Subsequent chemotherapy (BEP regimen)
      has brought regression of tumour and significant improvement in haemodynamic
      parameters (relief of pressure gradient in pulmonary artery). During the second
      surgery, the resection of all accessible tumour mass together with marginal
      resection of the right upper lobe was performed. No signs of cardiac or great
      vessels infiltration was found. Histopathologic examination revealed the necrotic
      masses and neoplastic foci diagnosed as teratoma immaturum. In a four-month
      follow-up the patient's condition remained good. The patient is still under the
      care of both oncological and cardiological specialists. Thus far he has not
      required further chemotherapy. Holter ECG monitoring revealed no arrhythmia, but
      the patient is still treated with mexiletine. The patient is planning to return
      to work. 

PMID- 25754059
TI  - Thixotropy of nasal medications-its role in clinical practice.
AB  - Optimal medication should be characterized by good bioavailability, rapid onset
      of action, a long period of therapeutic activity, with preserved high safety
      profile and the lowest possible risk of side effects. Therefore, in addition to
      traditional drug administration routes, such as oral or injection, novel methods
      for drug applications, for example in the form of a nasal application have been
      developed. Because of the anatomy of the nose, drugs administered intranasally
      can be rapidly absorbed and, depending on the nature of the active substance, may
      act locally on the mucosa or can have a significant systemic effect. Most nasal
      drugs are developed in the form of solution administered as aerosol. In some
      cases, these solutions are thixotropic. They are able to change their physical
      properties under agitation to facilitate supply of the drug and its adhesion to
      the mucosa. Intranasal corticosteroids represent the mainstay of treatment for
      any form of chronic allergic rhinitis (AR) and moderate to severe periodic AR,
      especially with impaired nasal obstruction and frequent occurrence of symptoms.
      The article discusses the rheological properties of intranasal corticosteroids,
      their role in therapy and efficacy in the everyday clinical practice. 

PMID- 25754060
TI  - Cardiovascular safety of two bronchodilators' fixed-dose combination: indacaterol
      and glycopyrronium.
AB  - Combination therapy with anticholinergics and beta2-agonists should be used in
      COPD patients after failure of previous monotherapy with one of these drugs.
      Synergistic effect of both mechanisms of bronchodilation can maximize the
      efficacy of separately administered drugs. The effectiveness of the combination
      of LABA and LAMA is already confirmed, nevertheless the question about the safety
      profile of this therapy is still remaining, particularly with regard to the
      cardiovascular system. The paper discusses the overall safety profile of the
      combined preparation compare to placebo as well as the active comparators,
      especially the cardiovascular safety of fixed-dose formulation. Based on the data
      it has been demonstrated, that the combination of two ultra-long-acting
      bronchodilators with different complementary mechanisms of action increases the
      effectiveness of COPD therapy without affecting the safety.

PMID- 25754061
TI  - The diminishing returns of robotic diffusion: complications after robot-assisted
      radical prostatectomy.

PMID- 25754062
TI  - Conceptual analysis of suffering in cancer: a systematic review.
AB  - OBJECTIVE: Patient suffering is a neglected area of care, partly because of poor
      definitions. The aim of this study was to distill what is currently known about
      suffering in the health literature in order to generate a conceptual basis for
      further research. METHODS: A systematic review focusing on suffering across all
      cancers was undertaken. The search included peer-reviewed English articles
      published between 1992 and 2012 in MEDLINE, Embase, PsycINFO and the Cochrane
      Library databases focusing on conceptualisation of suffering in adult cancer
      patients. Seminal theoretical articles conceptualising suffering more generally
      were also eligible. To ensure identification of a sufficiently broad range of
      conceptualisations of suffering in cancer, the search strategy was drafted
      iteratively. Study findings were subjected to conceptual analysis using the
      evolutionary method. RESULTS: One hundred twenty-eight studies were identified,
      which discussed definitions or conceptualisations of suffering. In terms of its
      attributes, suffering is defined as 'an all-encompassing, dynamic, individual
      phenomenon characterized by the experience of alienation, helplessness,
      hopelessness and meaninglessness in the sufferer which is difficult for them to
      articulate. It is multi-dimensional and usually incorporates an undesirable,
      negative quality.' Surrogate terms, antecedents and consequences of suffering are
      described. CONCLUSIONS: The systematic review revealed that suffering includes
      holistic suffering, which is multidimensional, oscillating, individual and
      difficult for individuals to express. Opportunities should be provided for
      patients to express their suffering. The potential for suffering to be
      transcended needs to be recognized and facilitated by healthcare staff.

PMID- 25754064
TI  - Infantile systemic hyalinosis in an Iranian family with a mutation in the
      CMG2/ANTXR2 gene.
AB  - Infantile systemic hyalinosis (ISH) is an extremely rare genodermatosis,
      characterized by thickened skin, joint contractures and subcutaneous nodules. ISH
      is caused by mutations in the CMG2 gene, which encodes a protein of unknown
      function. In this report, we describe a patient with ISH, who was a twin born to
      a consanguineous Iranian couple, and who demonstrated unusual skin findings in
      addition to the characteristic features of ISH. Mutation analysis disclosed a
      homozygous deletion mutation, c.1074delT in CMG2, resulting in a frameshift and
      premature termination codon 50 amino acids downstream of the deletion. This
      information adds to the recurring nature of this mutation in ISH, with
      implications for genetic counselling in extended families with a history of this
      disease. 

PMID- 25754065
TI  - Synergism of regulatory elements in sigma(B)- and sigma(A)-dependent promoters
      enhances recombinant protein expression in Bacillus subtilis.
AB  - Strong promoter is an essential factor for production of recombinant protein in
      various expression systems including Bacillus subtilis. In this study, we
      described a strategy to improve the expression efficiency using synthetic double
      promoter. Assembly of the conserved elements from sigma(B)- and sigma(A)
      dependent promoters constitutively improved the yield of recombinant protein
      approximately 2-3-fold in both exponential and stationary growth phase. The
      synergistic effect in the double promoter was observed only when sigma(B)
      promoter was located upstream to sigma(A)-promoter but independent to its
      orientation. A conserved element in either -10 or -35 box of sigma(B)-promoter is
      sufficient to promote the synergism. Hence, this simple strategy of promoter
      engineering could be an effective way to generate a pool of strong constitutive
      promoters applicable for heterologous protein expression in B. subtilis in the
      future. 

PMID- 25754063
TI  - 'I was thinking too much': experiences of HIV-positive adults with common mental
      disorders and poor adherence to antiretroviral therapy in Zimbabwe.
AB  - OBJECTIVE: To document the lived experiences of people with both poor mental
      health and suboptimal adherence to antiretroviral therapy in high HIV prevalence
      settings. METHODS: In-depth qualitative interviews were conducted with 47 (female
      = 31) HIV-positive adults who scored above the cut-point on a locally validated
      scale for common mental disorders (CMDs). Purposive sampling was used to recruit
      participants with evidence of poor adherence. Six additional key informant
      interviews (female = 6) were conducted with healthcare workers. Data were
      collected and analysed inductively by an interdisciplinary coding team. RESULTS:
      The major challenges faced by participants were stressors (poverty, stigma,
      marital problems) and symptoms of CMDs ('thinking too much', changes to appetite
      and sleep, 'burdened heart' and low energy levels). Thinking too much, which
      appears closely related to rumination, was the symptom with the greatest negative
      impact on adherence to antiretroviral therapy among HIV-positive adults with
      CMDs. In turn, thinking too much was commonly triggered by the stressors faced by
      people living with HIV/AIDS, especially poverty. Finally, participants desired
      private counselling, access to income-generating activities and family engagement
      in mental health care. CONCLUSIONS: Better understanding of the local expression
      of mental disorders and of underlying stressors can inform the development of
      culturally sensitive interventions to reduce CMDs and poor adherence to
      antiretroviral therapy.

PMID- 25754066
TI  - Using L-arginine-functionalized gold nanorods for visible detection of
      mercury(II) ions.
AB  - A rapid and simple approach for visible determination of mercury ions (Hg(2+) )
      in aqueous solutions was developed based on surface plasmon resonance phenomenon
      using L-arginine-functionalized gold nanorods (AuNRs). At pH greater than 9, the
      deprotonated amine group of L-arginine on the AuNRs bound with Hg(2+) leading to
      the side-by-side assembly of AuNRs, which was verified by transmission electron
      microscopy images. Thus, when Hg(2+) was present in the test solution, a blue
      shift of the typical longitudinal plasmon band of the AuNRs was observed in the
      ultra violet-visible-near infrared (UV-Vis-NIR) spectra, along with a change in
      the color of the solution, which occurred within 5 min. After carefully
      optimizing the potential factors affecting the performance, the L-arginine/AuNRs
      sensing system was found to be highly sensitive to Hg(2+) , with the limit of
      detection of 5 nM (S/N = 3); it is also very selective and free of interference
      from 10 other metal ions (Ba(2+) , Ca(2+) , Cd(2+) , Co(2+) , Cs(+) , Cu(2+) ,
      K(+) , Li(+) , Ni(2+) , Pb(2+) ). The result suggests that the L-arginine
      functionalized AuNRs can potentially serve as a rapid, sensitive, and easy-to-use
      colorimetric biosensor useful for determining Hg(2+) in food and environmental
      samples. 

PMID- 25754067
TI  - Single-atom gold catalysis in the context of developments in parahydrogen-induced
      polarization.
AB  - A highly isolated monoatomic gold catalyst, with single gold atoms dispersed on
      multiwalled carbon nanotubes (MWCNTs), has been synthesized, characterized, and
      tested in heterogeneous hydrogenation of 1,3-butadiene and 1-butyne with
      parahydrogen to maximize the polarization level and the contribution of the
      pairwise hydrogen addition route. The Au/MWCNTs catalyst was found to be active
      and efficient in pairwise hydrogen addition and the estimated contributions from
      the pairwise hydrogen addition route are at least an order of magnitude higher
      than those for supported metal nanoparticle catalysts. Therefore, the use of the
      highly isolated monoatomic catalysts is very promising for production of
      hyperpolarized fluids that can be used for the significant enhancement of NMR
      signals. A mechanism of 1,3-butadiene hydrogenation with parahydrogen over the
      highly isolated monoatomic Au/MWCNTs catalyst is also proposed. 

PMID- 25754068
TI  - Spatial frequency processing in scene-selective cortical regions.
AB  - Visual analysis begins with the parallel extraction of different attributes at
      different spatial frequencies. Low spatial frequencies (LSF) convey coarse
      information and are characterized by high luminance contrast, while high spatial
      frequencies (HSF) convey fine details and are characterized by low luminance
      contrast. In the present fMRI study, we examined how scene-selective regions-the
      parahippocampal place area (PPA), the retrosplenial cortex (RSC) and the
      occipital place area (OPA)-responded to spatial frequencies when contrast was
      either equalized or not equalized across spatial frequencies. Participants
      performed a categorization task on LSF, HSF and non-filtered scenes belonging to
      two different categories (indoors and outdoors). We either left contrast across
      scenes untouched, or equalized it using a root-mean-square contrast
      normalization. We found that when contrast remained unmodified, LSF and NF scenes
      elicited greater activation than HSF scenes in the PPA. However, when contrast
      was equalized across spatial frequencies, the PPA was selective to HFS. This
      suggests that PPA activity relies on an interaction between spatial frequency and
      contrast in scenes. In the RSC, LSF and NF elicited greater response than HSF
      scenes when contrast was not modified, while no effect of spatial frequencies
      appeared when contrast was equalized across filtered scenes, suggesting that the
      RSC is sensitive to high-contrast information. Finally, we observed selective
      activation of the OPA in response to HSF, irrespective of contrast manipulation.
      These results provide new insights into how scene-selective areas operate during
      scene processing. 

PMID- 25754069
TI  - The impact of mental workload on inhibitory control subprocesses.
AB  - The inhibition of inappropriate responses is a function known to rely on
      prefrontal cortex (PFC) functioning. Similarly, working memory processes are
      known to rely on the PFC. Even though these processes are usually closely
      intertwined and the functional neuroanatomy underlying these processes is largely
      overlapping, the influence of working memory load on inhibitory control process
      has remained largely elusive. In the current study, we therefore examine how
      response inhibition processes are modulated by working memory load. For this, we
      systematically increased the working memory load of participants by integrating
      mental rotation processes in a Go/NoGo paradigm. To examine the system
      neurophysiology of these processes in detail, and to examine whether there are
      differential effects of working memory load on distinct response inhibition
      subprocesses, we applied event-related potentials (ERPs) in combination with
      source localization techniques. The data shows that after exceeding a certain
      threshold, inhibitory control processes are aggravated by working memory load.
      The neurophysiological data paralleled the behavioral data. However, it suggests
      that distinguishable response inhibition subprocesses are differentially
      modulated by working memory load: Changes were evident in the NoGo-P3 amplitude
      but not in the NoGo-N2 amplitude. On a system level, this distinctive modulation
      of response inhibition subprocesses was related to differences in neural activity
      in the left inferior and middle frontal gyri. We show that inhibitory control
      processes are impaired when the working memory load surpasses a certain
      threshold. This, however only applies to situations in which the necessity of
      inhibitory control processes cannot be easily detected on the basis of perceptual
      factors. 

PMID- 25754070
TI  - State and parameter estimation of a neural mass model from electrophysiological
      signals during the status epilepticus.
AB  - Status epilepticus is an emergency condition in patients with prolonged seizure
      or recurrent seizures without full recovery between them. The pathophysiological
      mechanisms of status epilepticus are not well established. With this argument, we
      use a computational modeling approach combined with in vivo electrophysiological
      data obtained from an experimental model of status epilepticus to infer about
      changes that may lead to a seizure. Special emphasis is done to analyze parameter
      changes during or after pilocarpine administration. A cubature Kalman filter is
      utilized to estimate parameters and states of the model in real time from the
      observed electrophysiological signals. It was observed that during basal activity
      (before pilocarpine administration) the parameters presented a standard deviation
      below 30% of the mean value, while during SE activity, the parameters presented
      variations larger than 200% of the mean value with respect to basal state. The
      ratio of excitation-inhibition, increased during SE activity by 80% with respect
      to the transition state, and reaches the lowest value during cessation. In
      addition, a progression between low and fast inhibitions before or during this
      condition was found. This method can be implemented in real time, which is
      particularly important for the design of stimulation devices that attempt to stop
      seizures. These changes in the parameters analyzed during seizure activity can
      lead to better understanding of the mechanisms of epilepsy and to improve its
      treatments.

PMID- 25754071
TI  - Conserved transcriptional responses to cyanobacterial stressors are mediated by
      alternate regulation of paralogous genes in Daphnia.
AB  - Despite a significant increase in genomic data, our knowledge of gene functions
      and their transcriptional responses to environmental stimuli remains limited.
      Here, we use the model keystone species Daphnia pulex to study environmental
      responses of genes in the context of their gene family history to better
      understand the relationship between genome structure and gene function in
      response to environmental stimuli. Daphnia were exposed to five different
      treatments, each consisting of a diet supplemented with one of five
      cyanobacterial species, and a control treatment consisting of a diet of only
      green algae. Differential gene expression profiles of Daphnia exposed to each of
      these five cyanobacterial species showed that genes with known functions are more
      likely to be shared by different expression profiles, whereas genes specific to
      the lineage of Daphnia are more likely to be unique to a given expression
      profile. Furthermore, while only a small number of nonlineage-specific genes were
      conserved across treatment type, there was a high degree of overlap in expression
      profiles at the functional level. The conservation of functional responses across
      the different cyanobacterial treatments can be attributed to the treatment
      specific expression of different paralogous genes within the same gene family.
      Comparison with available gene expression data in the literature suggests
      differences in nutritional composition in diets with cyanobacterial species
      compared to diets of green algae as a primary driver for cyanobacterial effects
      on Daphnia. We conclude that conserved functional responses in Daphnia across
      different cyanobacterial treatments are mediated through alternate regulation of
      paralogous gene families. 

PMID- 25754072
TI  - The fatty acid binding protein 6 gene (Fabp6) is expressed in murine granulosa
      cells and is involved in ovulatory response to superstimulation.
AB  - The fatty acid binding protein 6 (Fabp6) is commonly regarded as a bile acid
      binding protein found in the distal portion of the small intestine and has been
      shown to be important in maintaining bile acid homeostasis. Previous studies have
      also reported the presence of Fabp6 in human, rat and fish ovaries, but the
      significance of Fabp6 in this organ is largely unknown. Therefore, we surveyed
      murine ovaries for Fabp6 gene expression and evaluated its role in ovarian
      function using mice with whole body Fabp6 deficiency. Here we show that the Fabp6
      gene is expressed in granulosa and luteal cells of the mouse ovary. Treatment
      with gonadotropins stimulated Fabp6 gene expression in large antral follicles.
      The ovulation rate in response to superovulatory treatment in Fabp6-deficient
      mice was markedly decreased compared to wildtype (C57BL/6) mice. The results of
      this study suggest that expression of Fabp6 gene in granulosa cells serves an
      important and previously unrecognized function in fertility. 

PMID- 25754073
TI  - Nothing fails like success--the great immunization debate.

PMID- 25754074
TI  - Coronary Artery Calcium Assessment in CKD: Utility in Cardiovascular Disease Risk
      Assessment and Treatment?
AB  - Coronary artery calcification (CAC) is a strong predictor of cardiovascular event
      rates in the general population, and scoring with multislice computed tomography
      commonly is used to improve risk stratification beyond clinical variables. CAC is
      accelerated in chronic kidney disease, but this occurs as a result of 2 distinct
      pathologic processes that result in medial (arteriosclerosis) and intimal
      (atherosclerosis) deposition. Although there are data that indicate that very
      high CAC scores may be associated with increased risk of death in hemodialysis,
      average CAC scores in most patients are elevated at a level at which
      discriminatory power may be reduced. There is a lack of data to guide management
      strategies in these patients based on CAC scores. There are even fewer data
      available for nondialysis patients, and it is uncertain whether CAC score confers
      an elevated risk of premature cardiovascular morbidity and mortality in such
      patients. In this article, we review the evidence regarding the utility of CAC
      score for noninvasive cardiovascular risk assessment in individuals with chronic
      kidney disease, using a clinical vignette that highlights some of the limitations
      in using CAC score and considerations in risk stratification. 

PMID- 25754075
TI  - Multi-output model with Box-Jenkins operators of linear indices to predict multi
      target inhibitors of ubiquitin-proteasome pathway.
AB  - The ubiquitin-proteasome pathway (UPP) plays an important role in the degradation
      of cellular proteins and regulation of different cellular processes that include
      cell cycle control, proliferation, differentiation, and apoptosis. In this sense,
      the disruption of proteasome activity leads to different pathological states
      linked to clinical disorders such as inflammation, neurodegeneration, and cancer.
      The use of UPP inhibitors is one of the proposed approaches to manage these
      alterations. On other hand, the ChEMBL database contains >5,000 experimental
      outcomes for >2,000 compounds tested as possible proteasome inhibitors using a
      large number of pharmacological assay protocols. All these assays report a large
      number of experimental parameters of biological activity like EC50, IC50 percent
      of inhibition, and many others that have been determined under many different
      conditions, targets, organisms, etc. Although this large amount of data offers
      new opportunities for the computational discovery of proteasome inhibitors, the
      complexity of these data represents a bottleneck for the development of
      predictive models. In this work, we used linear molecular indices calculated with
      the software TOMOCOMD-CARDD and Box-Jenkins moving average operators to develop a
      multi-output model that can predict outcomes for 20 experimental parameters in
      >450 assays carried out under different conditions. This generated multi-output
      model showed values of accuracy, sensitivity, and specificity above 70% for
      training and validation series. Finally, this model is considered multi-target
      and multi-scale, because it predicts the inhibition of the UPP for drugs against
      22 molecular or cellular targets of different organisms contained in the ChEMBL
      database.

PMID- 25754076
TI  - Predicting antiprotozoal activity of benzyl phenyl ether diamine derivatives
      through QSAR multi-target and molecular topology.
AB  - Multi-target QSAR is a novel approach that can predict simultaneously the
      activity of a given chemical compound on different pharmacological targets. In
      this work, we have used molecular topology and statistical tools such as
      multilinear regression analysis and artificial neural networks, to achieve a
      multi-target QSAR model capable to predict the antiprotozoal activity of a group
      of benzyl phenyl ether diamine derivatives. The activity was related to three
      parasites with a high prevalence rate in humans: Trypanosoma brucei rhodesiense,
      Plasmodium falciparum, and Leishmania donovani. The multi-target model showed a
      high regression coefficient (R(2) = 0.9644 and R(2) = 0.9235 for training and
      test sets, respectively) and a low standard error of estimate (SEE = 0.279).
      Model validation was performed with an external test (R(2) = 0.9001) and a
      randomization analysis. Finally, the model was applied to the search of potential
      new active compounds.

PMID- 25754077
TI  - Synthesis and crystal structure of new heterocyles derived from saccharin and
      uracil carrying 1,2,4-oxadiazolylmethyl group.
AB  - Saccharin, uracil, and 1,2,4-oxadiazole heterocyles are important in terms of
      exhibiting various biological acitivities. In this work, four series of 1,2,4
      oxadiazolylmethyl-substituted saccharin, and uracil derivatives are synthesized
      and their structures are identified by means of spectral/physical
      characteristics. The first series are oxadiazolylmethyl-substituted saccharins.
      The second one is oxadiazole-substituted uracils which are obtained as a
      separable mixture of both mono- and bis-substituted end products. Third series is
      obtained from 5-amino uracil and chloromethyl oxadiazoles. The fourth group is
      oxadiazolyl methyl-substituted imino uracils. The structures of some title
      compounds are also confirmed by X-ray diffraction data. 

PMID- 25754078
TI  - Responses of wheat (Triticum aestivum) and turnip (Brassica rapa) to the combined
      exposure of carbaryl and ultraviolet radiation.
AB  - The increase of ultraviolet (UV) radiation reaching the Earth's surface as a
      result of increased ozone layer depletion has affected crop production systems
      and, in combination with pesticides used in agricultural activities, can lead to
      greater risks to the environment. The impact of UV radiation and carbaryl singly
      and in combination on Triticum aestivum (wheat) and Brassica rapa (turnip) was
      studied. The combined exposure was analyzed using the MixTox tool and was based
      on the conceptual model of independent action, where possible deviations to
      synergism or antagonism and dose-ratio or dose-level response pattern were also
      considered. Compared with the control, carbaryl and UV radiation individually led
      to reductions in growth, fresh and dry weight, and water content for both
      species. Combined treatment of UV and carbaryl was more deleterious compared with
      single exposure. For T. aestivum length, no interaction between the 2 stressors
      was found (independent action), and a dose-level deviation was the best
      description for the weight parameters. For B. rapa, dose-ratio deviations from
      the conceptual model were found when length and dry weight were analyzed, and a
      higher than expected effect on the fresh weight (synergism) occurred with
      combined exposure.

PMID- 25754079
TI  - Abnormal high-energy phosphate molecule metabolism during regional brain
      activation in patients with bipolar disorder.
AB  - Converging evidence suggests bioenergetic abnormalities in bipolar disorder (BD).
      In the brain, phosphocreatine (PCr) acts a reservoir of high-energy phosphate
      (HEP) bonds, and creatine kinases (CK) catalyze the transfer of HEP from
      adenosine triphosphate (ATP) to PCr and from PCr back to ATP, at times of
      increased need. This study examined the activity of this mechanism in BD by
      measuring the levels of HEP molecules during a stimulus paradigm that increased
      local energy demand. Twenty-three patients diagnosed with BD-I and 22 healthy
      controls (HC) were included. Levels of phosphorus metabolites were measured at
      baseline and during visual stimulation in the occipital lobe using (31)P magnetic
      resonance spectroscopy at 4T. Changes in metabolite levels showed different
      patterns between the groups. During stimulation, HC had significant reductions in
      PCr but not in ATP, as expected. In contrast, BD patients had significant
      reductions in ATP but not in PCr. In addition, PCr/ATP ratio was lower at
      baseline in patients, and there was a higher change in this measure during
      stimulation. This pattern suggests a disease-related failure to replenish ATP
      from PCr through CK enzyme catalysis during tissue activation. Further studies
      measuring the CK flux in BD are required to confirm and extend this finding. 

PMID- 25754080
TI  - Common polygenic risk for autism spectrum disorder (ASD) is associated with
      cognitive ability in the general population.
AB  - Cognitive impairment is common among individuals diagnosed with autism spectrum
      disorder (ASD) and attention-deficit hyperactivity disorder (ADHD). It has been
      suggested that some aspects of intelligence are preserved or even superior in
      people with ASD compared with controls, but consistent evidence is lacking. Few
      studies have examined the genetic overlap between cognitive ability and ASD/ADHD.
      The aim of this study was to examine the polygenic overlap between ASD/ADHD and
      cognitive ability in individuals from the general population. Polygenic risk for
      ADHD and ASD was calculated from genome-wide association studies of ASD and ADHD
      conducted by the Psychiatric Genetics Consortium. Risk scores were created in
      three independent cohorts: Generation Scotland Scottish Family Health Study
      (GS:SFHS) (n=9863), the Lothian Birth Cohorts 1936 and 1921 (n=1522), and the
      Brisbane Adolescent Twin Sample (BATS) (n=921). We report that polygenic risk for
      ASD is positively correlated with general cognitive ability (beta=0.07, P=6 * 10(
      7), r(2)=0.003), logical memory and verbal intelligence in GS:SFHS. This was
      replicated in BATS as a positive association with full-scale intelligent quotient
      (IQ) (beta=0.07, P=0.03, r(2)=0.005). We did not find consistent evidence that
      polygenic risk for ADHD was associated with cognitive function; however, a
      negative correlation with IQ at age 11 years (beta=-0.08, Z=-3.3, P=0.001) was
      observed in the Lothian Birth Cohorts. These findings are in individuals from the
      general population, suggesting that the relationship between genetic risk for ASD
      and intelligence is partly independent of clinical state. These data suggest that
      common genetic variation relevant for ASD influences general cognitive ability. 

PMID- 25754081
TI  - Evaluating historical candidate genes for schizophrenia.
AB  - Prior to the genome-wide association era, candidate gene studies were a major
      approach in schizophrenia genetics. In this invited review, we consider the
      current status of 25 historical candidate genes for schizophrenia (for example,
      COMT, DISC1, DTNBP1 and NRG1). The initial study for 24 of these genes explicitly
      evaluated common variant hypotheses about schizophrenia. Our evaluation included
      a meta-analysis of the candidate gene literature, incorporation of the results of
      the largest genomic study yet published for schizophrenia, ratings from informed
      researchers who have published on these genes, and ratings from 24 schizophrenia
      geneticists. On the basis of current empirical evidence and mostly consensual
      assessments of informed opinion, it appears that the historical candidate gene
      literature did not yield clear insights into the genetic basis of schizophrenia.
      A likely reason why historical candidate gene studies did not achieve their
      primary aims is inadequate statistical power. However, the considerable efforts
      embodied in these early studies unquestionably set the stage for current
      successes in genomic approaches to schizophrenia. 

PMID- 25754082
TI  - Gene networks specific for innate immunity define post-traumatic stress disorder.
AB  - The molecular factors involved in the development of Post-Traumatic Stress
      Disorder (PTSD) remain poorly understood. Previous transcriptomic studies
      investigating the mechanisms of PTSD apply targeted approaches to identify
      individual genes under a cross-sectional framework lack a holistic view of the
      behaviours and properties of these genes at the system-level. Here we sought to
      apply an unsupervised gene-network based approach to a prospective experimental
      design using whole-transcriptome RNA-Seq gene expression from peripheral blood
      leukocytes of U.S. Marines (N=188), obtained both pre- and post-deployment to
      conflict zones. We identified discrete groups of co-regulated genes (i.e., co
      expression modules) and tested them for association to PTSD. We identified one
      module at both pre- and post-deployment containing putative causal signatures for
      PTSD development displaying an over-expression of genes enriched for functions of
      innate-immune response and interferon signalling (Type-I and Type-II).
      Importantly, these results were replicated in a second non-overlapping
      independent dataset of U.S. Marines (N=96), further outlining the role of innate
      immune and interferon signalling genes within co-expression modules to explain at
      least part of the causal pathophysiology for PTSD development. A second module,
      consequential of trauma exposure, contained PTSD resiliency signatures and an
      over-expression of genes involved in hemostasis and wound responsiveness
      suggesting that chronic levels of stress impair proper wound healing during/after
      exposure to the battlefield while highlighting the role of the hemostatic system
      as a clinical indicator of chronic-based stress. These findings provide novel
      insights for early preventative measures and advanced PTSD detection, which may
      lead to interventions that delay or perhaps abrogate the development of PTSD. 

PMID- 25754083
TI  - Genetic link between family socioeconomic status and children's educational
      achievement estimated from genome-wide SNPs.
AB  - One of the best predictors of children's educational achievement is their
      family's socioeconomic status (SES), but the degree to which this association is
      genetically mediated remains unclear. For 3000 UK-representative unrelated
      children we found that genome-wide single-nucleotide polymorphisms could explain
      a third of the variance of scores on an age-16 UK national examination of
      educational achievement and half of the correlation between their scores and
      family SES. Moreover, genome-wide polygenic scores based on a previously
      published genome-wide association meta-analysis of total number of years in
      education accounted for ~3.0% variance in educational achievement and ~2.5% in
      family SES. This study provides the first molecular evidence for substantial
      genetic influence on differences in children's educational achievement and its
      association with family SES. 

PMID- 25754084
TI  - The impact of chronic stress on the rat brain lipidome.
AB  - Chronic stress is a major risk factor for several human disorders that affect
      modern societies. The brain is a key target of chronic stress. In fact, there is
      growing evidence indicating that exposure to stress affects learning and memory,
      decision making and emotional responses, and may even predispose for pathological
      processes, such as Alzheimer's disease and depression. Lipids are a major
      constituent of the brain and specifically signaling lipids have been shown to
      regulate brain function. Here, we used a mass spectrometry-based lipidomic
      approach to evaluate the impact of a chronic unpredictable stress (CUS) paradigm
      on the rat brain in a region-specific manner. We found that the prefrontal cortex
      (PFC) was the area with the highest degree of changes induced by chronic stress.
      Although the hippocampus presented relevant lipidomic changes, the amygdala and,
      to a greater extent, the cerebellum presented few lipid changes upon chronic
      stress exposure. The sphingolipid and phospholipid metabolism were profoundly
      affected, showing an increase in ceramide (Cer) and a decrease in sphingomyelin
      (SM) and dihydrosphingomyelin (dhSM) levels, and a decrease in
      phosphatidylethanolamine (PE) and ether phosphatidylcholine (PCe) and increase in
      lysophosphatidylethanolamine (LPE) levels, respectively. Furthermore, the fatty
      acyl profile of phospholipids and diacylglycerol revealed that chronic stressed
      rats had higher 38 carbon(38C)-lipid levels in the hippocampus and reduced 36C
      lipid levels in the PFC. Finally, lysophosphatidylcholine (LPC) levels in the PFC
      were found to be correlated with blood corticosterone (CORT) levels. In summary,
      lipidomic profiling of the effect of chronic stress allowed the identification of
      dysregulated lipid pathways, revealing putative targets for pharmacological
      intervention that may potentially be used to modulate stress-induced deficits. 

PMID- 25754086
TI  - Response to Robinson et al.

PMID- 25754085
TI  - Neural transcriptome of constitutional Pten dysfunction in mice and its relevance
      to human idiopathic autism spectrum disorder.
AB  - Autism spectrum disorder (ASD) is a neurodevelopmental condition with a clear,
      but heterogeneous, genetic component. Germline mutations in the tumor suppressor
      Pten are a well-established risk factor for ASD with macrocephaly, and
      conditional Pten mouse models have impaired social behavior and brain
      development. Some mutations observed in patients disrupt the normally balanced
      nuclear-cytoplasmic localization of the Pten protein, and we developed the
      Pten(m3m4) model to study the effects of a cytoplasm-predominant Pten. In this
      model, germline mislocalization of Pten causes inappropriate social behavior with
      intact learning and memory, a profile reminiscent of high-functioning ASD. These
      animals also exhibit histological evidence of neuroinflammation and expansion of
      glial populations by 6 weeks of age. We hypothesized that the neural
      transcriptome of this model would be altered in a manner that could inform human
      idiopathic ASD, a constitutional condition. Using total RNA sequencing, we found
      progressive disruption of neural gene expression in Pten(m3m4) mice from 2-6
      weeks of age, involving both immune and synaptic pathways. These alterations
      include downregulation of many highly coexpressed human ASD-susceptibility genes.
      Comparison with a human cortical development coexpression network revealed that
      genes disrupted in Pten(m3m4) mice were enriched in the same areas as those of
      human ASD. Although Pten-related ASD is relatively uncommon, our observations
      suggest that the Pten(m3m4) model recapitulates multiple molecular features of
      human ASD, and that Pten operates far upstream of common pathways within ASD
      pathogenesis. 

PMID- 25754087
TI  - Prognostic value of long noncoding RNA HOTAIR in digestive system malignancies.
AB  - BACKGROUND AND AIM: HOX transcript antisense intergenic RNA (HOTAIR), a well
      known long noncoding RNA, has been found to play significant roles in several
      tumors. However, the clinical application value of HOTAIR in digestive system
      malignancies remains to be clarified. We aimed to explore comprehensively the
      potential role of HOTAIR as a prognostic indicator in digestive system
      malignancies. METHODS: Systematic search was performed in Pubmed, Embase,
      Cochrane Library, and Web of Science until July 5, 2014. A quantitative meta
      analysis was conducted with standard statistical methods for eligible papers on
      the prognostic value of HOTAIR in digestive system cancers. RESULTS: A total of
      1059 patients from 13 studies were included in the meta-analysis. A significant
      association was found between HOTAIR abundance and poor overall survival (OS) of
      patients with digestive system malignancies, with pooled hazard ratio (HR) of
      2.587 (95% confidence interval [CI]: 2.054-3.259, P < 0.001). By combining HRs
      from Cox multivariate analyses, we found HOTAIR was an independent prognostic
      factor for OS without obvious heterogeneity (HR: 2.405, 95% CI: 1.883-3.0722, P <
      0.001). Subgroup analysis showed that tumor type, histology type, region,
      publication year, sample size, and quality score did not alter the predictive
      value of HOTAIR as an independent factor for survival. Meta-regression and
      sensitivity analysis both suggested the reliability of our findings. A slight
      publication bias was observed. After adjustment by nonparametric "trim-and-fill"
      method, the corrected HRs had no significant change. CONCLUSION: HOTAIR could be
      exploited as a novel prognostic biomarker for patients with digestive system
      malignancies.

PMID- 25754089
TI  - Relative cerebral blood volume is a potential predictive imaging biomarker of
      bevacizumab efficacy in recurrent glioblastoma.
AB  - BACKGROUND: To analyze the relevance of dynamic susceptibility-weighted contrast
      enhanced MRI (DSC-MRI) derived relative cerebral blood volume (rCBV) analysis for
      predicting response to bevacizumab (BEV) in patients with recurrent glioblastoma
      (rGB). METHODS: A total of 127 patients diagnosed with rGB receiving either
      bevacizumab (71 patients, BEV cohort) or alkylating chemotherapy (56 patients,
      non-BEV cohort) underwent conventional anatomic MRI and DSC-MRI at baseline and
      at first follow-up after treatment initiation. The mean rCBV of the contrast
      enhancing tumor (cT1) as well as cT1 and fluid-attenuated inversion recovery
      (FLAIR) volumes at both time points were correlated with progression-free
      survival (PFS) and overall survival (OS) using Cox proportional hazard models,
      logistic regression, and the log-rank test. RESULTS: Baseline rCBV was associated
      with both PFS (hazard ratio [HR] = 1.3; P < .01) and OS (HR = 1.3; P < .01) in
      the BEV cohort and predicted 6-month PFS in 82% and 12-month OS in 79% of
      patients, whereas it was not associated with PFS (HR = 1.0; P = .70) or OS (HR =
      1.0; P = .47) in the non-BEV cohort. Corresponding median OS and PFS rates in the
      BEV cohort for patients with rCBV-values less than 3.92 (optimal threshold from
      receiver operating characteristic [ROC] analysis of 12-month OS data) were 14.2
      and 6.0 months, as compared to 6.6 and 2.8 months for patients with rCBV-values
      greater than 3.92 (P < .01, respectively). cT1 and FLAIR volumes at first follow
      up were significant predictors of 6-month PFS and 12-month OS in the BEV cohort
      but not in the non-BEV cohort. Corresponding volumes at baseline were not
      significant in any cohort. CONCLUSIONS: Pretreatment rCBV is a potential
      predictive imaging biomarker in BEV-treated rGB but not alkylating chemotherapy
      treated rGB, which is superior to volumetric analysis of conventional anatomic
      MRI and predicts 6-month PFS and 12-month OS in 80% of BEV-treated patients.

PMID- 25754090
TI  - Tregs in gliomas - the jury is still out.

PMID- 25754088
TI  - Clinical implementation of integrated whole-genome copy number and mutation
      profiling for glioblastoma.
AB  - BACKGROUND: Multidimensional genotyping of formalin-fixed paraffin-embedded
      (FFPE) samples has the potential to improve diagnostics and clinical trials for
      brain tumors, but prospective use in the clinical setting is not yet routine. We
      report our experience with implementing a multiplexed copy number and mutation
      testing program in a diagnostic laboratory certified by the Clinical Laboratory
      Improvement Amendments. METHODS: We collected and analyzed clinical testing
      results from whole-genome array comparative genomic hybridization (OncoCopy) of
      420 brain tumors, including 148 glioblastomas. Mass spectrometry-based mutation
      genotyping (OncoMap, 471 mutations) was performed on 86 glioblastomas. RESULTS:
      OncoCopy was successful in 99% of samples for which sufficient DNA was obtained
      (n = 415). All clinically relevant loci for glioblastomas were detected,
      including amplifications (EGFR, PDGFRA, MET) and deletions (EGFRvIII, PTEN,
      1p/19q). Glioblastoma patients <=40 years old had distinct profiles compared with
      patients >40 years. OncoMap testing reliably identified mutations in IDH1, TP53,
      and PTEN. Seventy-seven glioblastoma patients enrolled on trials, of whom 51%
      participated in targeted therapeutic trials where multiplex data informed
      eligibility or outcomes. Data integration identified patients with complete tumor
      suppressor inactivation, albeit rarely (5% of patients) due to lack of whole-gene
      coverage in OncoMap. CONCLUSIONS: Combined use of multiplexed copy number and
      mutation detection from FFPE samples in the clinical setting can efficiently
      replace singleton tests for clinical diagnosis and prognosis in most settings.
      Our results support incorporation of these assays into clinical trials as
      integral biomarkers and their potential to impact interpretation of results.
      Limited tumor suppressor variant capture by targeted genotyping highlights the
      need for whole-gene sequencing in glioblastoma.

PMID- 25754092
TI  - European consensus statement on leptospirosis in dogs and cats.
AB  - Leptospirosis is a zoonotic disease with a worldwide distribution affecting most
      mammalian species. Clinical leptospirosis is common in dogs but appears to be
      rare in cats. Both dogs and cats, however, can shed leptospires in the urine.
      This is problematic as it can lead to exposure of humans. The control of
      leptospirosis, therefore, is important not only from an animal but also from a
      public health perspective. The aim of this consensus statement is to raise
      awareness of leptospirosis and to outline the current knowledge on the
      epidemiology, clinical features, diagnostic tools, prevention and treatment
      measures relevant to canine and feline leptospirosis in Europe. 

PMID- 25754093
TI  - Defective podocyte insulin signalling through p85-XBP1 promotes ATF6-dependent
      maladaptive ER-stress response in diabetic nephropathy.
AB  - Endoplasmic reticulum (ER) stress is associated with diabetic nephropathy (DN),
      but its pathophysiological relevance and the mechanisms that compromise adaptive
      ER signalling in podocytes remain unknown. Here we show that nuclear
      translocation of the transcription factor spliced X-box binding protein-1 (sXBP1)
      is selectively impaired in DN, inducing activating transcription factor-6 (ATF6)
      and C/EBP homology protein (CHOP). Podocyte-specific genetic ablation of XBP1 or
      inducible expression of ATF6 in mice aggravates DN. sXBP1 lies downstream of
      insulin signalling and attenuating podocyte insulin signalling by genetic
      ablation of the insulin receptor or the regulatory subunits phosphatidylinositol
      3-kinase (PI3K) p85alpha or p85beta impairs sXBP1 nuclear translocation and
      exacerbates DN. Corroborating our findings from murine DN, the interaction of
      sXBP1 with p85alpha and p85beta is markedly impaired in the glomerular
      compartment of human DN. Thus, signalling via the insulin receptor, p85, and XBP1
      maintains podocyte homeostasis, while disruption of this pathway impairs podocyte
      function in DN. 

PMID- 25754094
TI  - A 'golden' SNP in CmOr governs the fruit flesh color of melon (Cucumis melo).
AB  - The flesh color of Cucumis melo (melon) is genetically determined, and can be
      white, light green or orange, with beta-carotene being the predominant pigment.
      We associated carotenoid accumulation in melon fruit flesh with polymorphism
      within CmOr, a homolog of the cauliflower BoOr gene, and identified CmOr as the
      previously described gf locus in melon. CmOr was found to co-segregate with fruit
      flesh color, and presented two haplotypes (alleles) in a broad germplasm
      collection, one being associated with orange flesh and the second being
      associated with either white or green flesh. Allelic variation of CmOr does not
      affect its transcription or protein level. The variation also does not affect its
      plastid subcellular localization. Among the identified single nucleotide
      polymorphisms (SNPs) between CmOr alleles in orange versus green/white-flesh
      fruit, a single SNP causes a change of an evolutionarily highly conserved
      arginine to histidine in the CmOr protein. Functional analysis of CmOr haplotypes
      in an Arabidopsis callus system confirmed the ability of the CmOr orange
      haplotype to induce beta-carotene accumulation. Site-directed mutagenesis of the
      CmOr green/white haplotype to change the CmOR arginine to histidine triggered
      beta-carotene accumulation. The identification of the 'golden' SNP in CmOr, which
      is responsible for the non-orange and orange melon fruit phenotypes, provides new
      tools for studying the Or mechanism of action, and suggests genome editing of the
      Or gene for nutritional biofortification of crops. 

PMID- 25754095
TI  - Insulin secretion abnormalities in exocrine pancreatic sufficient cystic fibrosis
      patients.
AB  - BACKGROUND: The aim of this study is to assess insulin secretion in pediatric
      cystic fibrosis (CF) patients with exocrine pancreatic sufficiency. METHODS:
      Glucose and insulin responses during an oral glucose tolerance test (OGTT) were
      measured in 146 CF patients. Patients were divided into exocrine sufficient (CF
      PS) and insufficient (CF-PI) groups based on pancreatic enzyme usage and fecal
      elastase. A reference group included healthy, non-diabetic subjects. RESULTS: All
      CF groups showed reduced insulin secretion as measured by insulinogenic index.
      The CF-PS patients had normal glucose tolerance. There was a direct correlation
      between BMI z-score and insulin area under the curve. CONCLUSION: Patients with
      CF have reduced insulin secretion during an OGTT regardless of exocrine
      pancreatic status. The abnormal insulin secretion in all CF patients may
      predispose them for glucose intolerance, particularly when challenged by
      inflammation, infection, or nutritional deficiency. In addition, the diminished
      insulin secretion may contribute to increased catabolism. Lastly, the CF-related
      diabetes (CFRD) screening guidelines should be followed by all CF patients
      regardless of pancreatic status.

PMID- 25754096
TI  - Treatment and demographic factors affecting time to next pulmonary exacerbation
      in cystic fibrosis.
AB  - BACKGROUND: Pulmonary exacerbations (PEx) are important CF clinical events.
      METHODS: We studied time to next PEx following intravenous (IV) antibiotic PEx
      treatment among Cleveland Ohio CF center patients occurring between January 2010
      and September 2014. Patient demographics, clinical presentations, and treatments
      were modeled by Cox proportional hazards regression to identify covariates
      associated with time to next PEx. RESULTS: 193 patients were treated for PEx; 155
      had a subsequent IV-treated PEx. Six covariates were associated with future PEx
      hazard: number of PEx in the prior year (hazard ratio 25.1 for >=3 and 4.4 for 1
      2 prior-year PEx versus none; P<.0001), IV treatment duration in weeks (1.2;
      P=.0004), percent hospital treatment (1.1; P=.0018), and chronic inhaled
      aminoglycosides (2.5; P<.0001), leukotriene modifiers (1.8; P=.0031), and high
      dose ibuprofen (0.52; P=.0006). CONCLUSIONS: Time to next PEx was profoundly
      associated with prior-year PEx, suggestive of high-risk PEx phenotypes that
      warrant recognition and further study.

PMID- 25754097
TI  - Effect of pulsed electric field treatment on hot-boned muscles of different
      potential tenderness.
AB  - In this study, the effect of pulsed electric field (PEF) treatment and ageing on
      the quality of beef M. longissimus lumborum (LL) and M. semimembranosus (SM)
      muscles was evaluated, including the tenderness, water loss and post-mortem
      proteolysis. Muscles were obtained from 12 steers (6 steers for each muscle),
      removed from the carcasses 4 hour postmortem and were treated with pulsed
      electric field within 2h. Six different pulsed electric field intensities
      (voltages of 5 and 10 kV * frequencies of 20, 50 and 90 Hz) plus a control were
      applied to each muscle to determine the optimum treatment conditions. Beef LL was
      found to get tougher with increasing treatment frequency whereas beef SM muscle
      was found to have up to 21.6% reduction in the shear force with pulsed electric
      field treatment. Post-mortem proteolysis showed an increase in both troponin and
      desmin degradation in beef LL treated with low intensity PEF treatment (20 Hz)
      compared to non-treated control samples.

PMID- 25754098
TI  - Melasma: clinical diagnosis and management options.
AB  - Melasma is a common acquired disorder of pigmentation most commonly seen in those
      with skin of colour. It has long been a condition that is frustrating for both
      the dermatologist and patient to treat. This article provides a review of the
      literature on melasma and examines, in detail, various treatment options
      currently available to treat it. 

PMID- 25754099
TI  - A new species of diplectanid (Monogenoidea) from Paranthias colonus (Perciformes,
      Serranidae) off Peru.
AB  - Pseudorhabdosynochus jeanloui n. sp. (Monogenoidea, Diplectanidae) is described
      from specimens collected from the gills of the Pacific creolefish, Paranthias
      colonus (Perciformes, Serranidae) from a fish market in Chorrillos, Lima, Peru.
      The new species is differentiated from other members of the genus by the
      structure of its sclerotized vagina, which has two spherical chambers of similar
      diameter. This is the first Pseudorhabdosynochus species described from the
      Pacific coast of America, the third species of the genus reported from South
      America and the first described from a member of Paranthias. 

PMID- 25754100
TI  - Inverted quantum dot light emitting diodes using polyethylenimine ethoxylated
      modified ZnO.
AB  - Colloidal quantum dots (QDs) are an emerging class of new materials due to their
      unique physical properties. In particular, colloidal QD based light emitting
      diodes (QDLEDs) have been extensively studied and developed for the next
      generation displays and solid-state lighting. Among a number of approaches to
      improve performance of the QDLEDs, the most practical one is optimization of
      charge transport and charge balance in the recombination region. Here, we suggest
      a polyethylenimine ethoxylated (PEIE) modified ZnO nanoparticles (NPs) as
      electron injection and transport layer for inverted structure red CdSe-ZnS based
      QDLED. The PEIE surface modifier, incorporated on the top of the ZnO NPs film,
      facilitates the enhancement of both electron injection into the CdSe-ZnS QD
      emissive layer by lowering the workfunction of ZnO from 3.58 eV to 2.87 eV and
      charge balance on the QD emitter. As a result, this device exhibits a low turn-on
      voltage of 2.0-2.5 V and has maximum luminance and current efficiency values of
      8600 cd/m(2) and current efficiency of 1.53 cd/A, respectively. The same scheme
      with ZnO NPs/PEIE layer has also been used to successfully fabricate green, blue,
      and white QDLEDs. 

PMID- 25754101
TI  - Airflow obstruction case finding in community-pharmacies: a novel strategy to
      reduce COPD underdiagnosis.
AB  - BACKGROUND: Community pharmacies (CP) have access to subjects at high-risk of
      suffering Chronic Obstructive Pulmonary Disease (COPD). We investigated if a COPD
      case finding program in CP could be a new strategy to reduce COPD underdiagnosis.
      METHODS: Prospective, cross-sectional, descriptive, uncontrolled, remotely
      supported study in 100 CP in Barcelona, Spain. Pharmacists were trained in a four
      day workshop on spirometry and COPD, and each was provided with a spirometer for
      12 weeks. The program included questionnaires and forced spirometry measurements,
      whose quality was controlled and monitored by web-assistance. FINDINGS: Overall
      2295 (73.5%), of 3121 CP customers invited to participate in the program
      accepted, and 1.456 (63.4%) were identified as "high risk" for COPD using the
      GOLD questionnaire. Only 33 could not conduct spirometry, and a pre
      bronchodilator airflow limitation (FEV1/FVC ratio <0.7) was confirmed in 282
      (19.8%); 244 of these were referred to their primary care (PC) physician for
      further diagnostic and therapeutic work-up, but only 39 of them (16%) fed-back
      this information to the pharmacist. Clinically acceptable quality spirometries
      (grade A or B) were obtained in 69.4% of the cases. CONCLUSION: This study shows
      that adequately trained and supported community pharmacists can effectively
      identify individuals at high risk of having COPD and can thus contribute to
      ameliorate underdiagnosis in this disease. Links between PC and CP should be
      improved to achieve a useful program.

PMID- 25754102
TI  - Evaluation of the potassium adsorption capacity of a potassium adsorption filter
      during rapid blood transfusion.
AB  - The concentration of extracellular potassium in red blood cell concentrates
      (RCCs) increases during storage, leading to risk of hyperkalemia. A potassium
      adsorption filter (PAF) can eliminate the potassium at normal blood transfusion.
      This study aimed to investigate the potassium adsorption capacity of a PAF during
      rapid blood transfusion. We tested several different potassium concentrations
      under a rapid transfusion condition using a pressure bag. The adsorption rates of
      the 70-mEq/l model were 76.8%. The PAF showed good potassium adsorption capacity,
      suggesting that this filter may provide a convenient method to prevent
      hyperkalemia during rapid blood transfusion. 

PMID- 25754103
TI  - Secular trends in body height and body mass in 19-year-old Polish men based on
      six national surveys from 1965 to 2010.
AB  - OBJECTIVES: The aim was to determine whether an intergenerational trend toward
      increased stature is slowing down, and whether body weight has recently increased
      among young men in Poland, as it has in Western European countries. METHODS: Data
      were taken from six national surveys of 19-year-old Polish male conscripts from
      cohorts 1965, 1976, 1986, 1995, 2001, and 2010. RESULTS: The mean stature of this
      population increased throughout the last 45 years from 170.5 cm in 1965 to 178.3
      in 2010. However, the average gain in stature per decade declined from 2.4 cm in
      the period 1965 to 1976 to 0.8 cm per decade in 1995 to 2001, but increased to
      1.0 cm in the last period. The average of body weight increased from 63.2 kg in
      1965 to 73.1 in 2010 and body mass index (BMI) rose from 21.73 to 22.94 in the
      same period. The tempo of increase varied in different periods; between 1965 and
      1986 an insignificant increase was observed (of circa 0.12); in 1986 to 1995
      there was no increase, whereas the period of 2001 to 2010 witnessed a significant
      increase (of circa 0.76). CONCLUSIONS: The trend of body size and stature
      increase within the Polish population, although decelerating, remained positive
      and steady during the last 45 years. No significant impact of the past half
      century's socioeconomic crises was observed in these measures of growth. We
      concluded that during the economic crises some effective mechanism protecting the
      living conditions of the children and youth were operating within the population.

PMID- 25754104
TI  - Reply: To PMID 25052507.

PMID- 25754105
TI  - Mortality after exposure to polychlorinated biphenyls and polychlorinated
      dibenzofurans: a meta-analysis of two highly exposed cohorts.
AB  - Both Yucheng and Yusho were events of accidental exposure to highly doses of
      polychlorinated biphenyls and dibenzofurans in Asian people. Mortality
      experiences caused by various diseases were reported in both cohorts with similar
      and dissimilar findings. We thus conducted a meta-analysis of two cohorts to
      reevaluate the effects of PCBs and PCDFs on major causes of mortalities. Two
      recently updated Yucheng and Yusho mortality studies were included. For selected
      diseases, standardized mortality ratios (SMR) and 95% confidence intervals (95%
      CI) were extracted. Meta-analyses were conducted using a random-effects model
      only when heterogeneity (I(2)  > 50% and/or p value <0.10 by the Q test) was not
      found. A total of 1,803 Yucheng subjects (male, N = 830; female, N = 973) with
      48,751 person-years of follow-up and 1,664 Yusho subjects (male, N = 860; female,
      N = 804) with 50,773 person-years are included. An increase in all-cause
      mortality (pooled SMR=1.2, 95% CI: 1.1-1.3, I(2)  = 0.0%), all cancers (pooled
      SMR=1.3, 95% CI: 1.1-1.6, I(2)  = 0.0%), lung cancer (pooled SMR=1.7, 95% CI: 1.2
      2.3, I(2) =0.0%), heart disease (pooled SMR=1.3, 95% CI: 1.0-1.7, I(2)  = 43.4%)
      and hepatic disease (pooled SMR=1.9, 95% CI: 1.3-2.8, I(2)  = 0.0%) were found in
      pooled males. Significant elevation from liver cancer was found in pooled females
      (pooled SMR=2.0, 95% CI: 1.1-3.6, I(2)  = 0.0%). This meta-analysis of Yucheng
      and Yusho cohorts showed similar elevation from all cancer, lung cancer, heart
      disease and hepatic disease mortalities in exposed men. Furthermore, a new
      finding of elevated liver cancer mortality in exposed women was identified. 

PMID- 25754107
TI  - Predictive value of the Groningen Frailty Indicator for treatment outcomes in
      elderly patients after head and neck, or skin cancer surgery in a retrospective
      cohort.
AB  - OBJECTIVES: Careful selection of patients eligible for extensive head and neck
      cancer surgery is extremely important. A reliable predictor for postoperative
      outcomes in the vulnerable elderly population is not yet available. The concept
      of frailty describes a clinical state of increased vulnerability and can be
      assessed using frailty tests, such as the Groningen Frailty Indicator. In the
      current study, the influence of Groningen Frailty Indicator-measured frailty on
      clinical outcome was investigated in elderly patients surgically treated for head
      and neck cancer. DESIGN: Retrospective, explorative cohort study. SETTING:
      Tertiary referral centre. PARTICIPANTS: A total of 90 patients of 65 years and
      older receiving surgical treatment for head and neck cancer with different
      primary sites. MAIN OUTCOME MEASURES: The influence of frailty (Groningen Frailty
      Indicator) on postoperative complications (Clavien-Dindo classification),
      subjective postoperative experience of both patient and surgeon and survival were
      analysed. RESULTS: A total of 36 patients were considered as frail (40%).
      Postoperative complications could not be predicted by frailty status. However,
      the Groningen Frailty Indicator dimension 'health problems' was a significant
      predictor for postoperative complications (P = 0.020). Unlike age and
      comorbidity, frailty was associated with a poor subjective patients' experience
      of the postoperative recovery (P < 0.01). Although not statistically significant,
      survival analysis showed a worse 5-year overall survival in the frail group (33%)
      versus the non-frail group (74%). CONCLUSIONS: Analysis of frailty could identify
      elderly patients who might suffer more than expected during the postoperative
      period after head and neck cancer surgery. In this study, frailty was not
      identified as a new predictor of complications after head and neck cancer
      surgery.

PMID- 25754106
TI  - IGF-1 drives chromogranin A secretion via activation of Arf1 in human
      neuroendocrine tumour cells.
AB  - Hypersecretion is the major symptom of functional neuroendocrine tumours. The
      mechanisms that contribute to this excessive secretion of hormones are still
      elusive. A key event in secretion is the exit of secretory products from the
      Golgi apparatus. ADP-ribosylation factor (Arf) GTPases are known to control
      vesicle budding and trafficking, and have a leading function in the regulation of
      formation of secretory granula at the Golgi. Here, we show that Arf1 is the
      predominant Arf protein family member expressed in the neuroendocrine pancreatic
      tumour cell lines BON and QGP-1. In BON cells Arf1 colocalizes with Golgi markers
      as well as chromogranin A, and shows significant basal activity. The inhibition
      of Arf1 activity or expression significantly impaired secretion of chromogranin
      A. Furthermore, we show that the insulin-like growth factor 1 (IGF-1), a major
      regulator of growth and secretion in BON cells, induces Arf1 activity. We found
      that activation of Arf1 upon IGF-1 receptor stimulation is mediated by MEK/ERK
      signalling pathway in BON and QGP-1 cells. Moreover, the activity of Arf1 in BON
      cells is mediated by autocrinely secreted IGF-1, and concomitantly, autocrine
      IGF1 secretion is maintained by Arf1 activity. In summary, our data indicate an
      important regulatory role for Arf1 at the Golgi in hypersecretion in
      neuroendocrine cancer cells. 

PMID- 25754108
TI  - The effectiveness of targeting never or rarely screened women in a national
      cervical cancer screening program for underserved women.
AB  - PURPOSE: To evaluate the effectiveness of a policy supporting early detection and
      prevention of cervical cancer among low-income and uninsured women by comparing
      women who reported never or rarely being screened (last screen >5 years) to those
      who reported screening in the past <=5 years. METHODS: We analyzed data from
      1,485,251 women who received their first Pap test in the National Breast and
      Cervical Cancer Early Detection Program (NBCCEDP) from July 2002 through June
      2012. Of these, 461,893 women (31 %) reported being never or rarely screened and
      1,023,358 (69 %) reported being screened in the past 5 years. Demographic (age,
      race/ethnicity, residence, and region) and clinic (cytologic and histologic
      results) characteristics were examined for the two groups. RESULTS: Women who
      were aged >=50 years, Asian and Pacific Islander, American Indian or Alaska
      Native, multiracial, living in non-metro areas, or living in the South or a
      territory were more likely to report being never or rarely screened. The
      percentage of abnormal Pap tests and the rate of precancer and cancer (combined)
      was higher in the never or rarely screened group compared with the screened group
      (abnormal percentage: 2.9 vs 2.6 %, p value < 0.01; rate of precancer and cancer:
      6.9 vs 3.7 per 1,000 women, p value < 0.01). CONCLUSIONS: The priority of
      reaching never or rarely screened women should continue since those women who
      entered the NBCCEDP not adequately screened had a greater prevalence of high
      grade histological lesions and invasive cervical cancers at later stages than
      women screened more recently.

PMID- 25754109
TI  - Reported breast symptoms in the National Breast and Cervical Cancer Early
      Detection Program.
AB  - PURPOSE: The frequency and types of breast symptoms reported by women in the
      National Breast and Cervical Cancer Early Detection Program (NBCCEDP) have never
      been characterized. This study aims to establish the frequency of reported
      symptoms and the diagnostic outcomes associated with reported symptoms. METHODS:
      We examined the frequency of symptoms reported prior to mammography using medical
      record abstraction data from women in the NBCCEDP. We also calculated adjusted
      odds ratios (aOR) of having an abnormal mammogram, an abnormal clinical breast
      examination, or a final diagnosis of breast cancer by symptoms, compared to
      asymptomatic women. RESULTS: In our sample of women, 10.3 % reported at least one
      symptom. Women with symptoms were younger and more likely to be non-Hispanic
      white. Among those reporting symptoms, breast lump (31.7 %) and pain or
      tenderness (49.3 %) was most common. A relatively low proportion of women with
      symptoms were diagnosed with in situ (0.9 %) or invasive breast cancer (4.3 %).
      However, a self-reported breast lump [aOR 13.7; 95 % confidence interval (CI) 7.8
      24.1], inflammation or changes to the skin/nipple (aOR 27.8; 95 % CI 8.7-88.8),
      and other or unspecified symptoms (aOR 3.4; 95 % CI 2.1-7.5) were associated with
      an increased risk of invasive breast cancer. CONCLUSIONS: Although the prevalence
      of breast cancer among women reporting symptoms is relatively low, knowing which
      symptoms carry the highest breast cancer risk is important to assist in
      appropriate diagnostic workup.

PMID- 25754110
TI  - Menstrual and reproductive history and use of exogenous sex hormones and risk of
      thyroid cancer among women: a meta-analysis of prospective studies.
AB  - PURPOSE: Thyroid cancer has a higher incidence in women than in men, and it has
      been hypothesized that hormonal factors may explain such disparity. We performed
      a meta-analysis of observational prospective studies to investigate the
      association between menstrual and reproductive variables and exogenous hormone
      use and the risk of thyroid cancer among women. METHODS: We calculated summary
      relative risks and 95% confidence intervals (95% CI) using random effect models.
      RESULTS: Overall, 5,434 thyroid cancer cases from twenty-four papers were
      included. Increasing age at first pregnancy/birth (SRR 1.56, 95% CI 1.01-2.42)
      and hysterectomy (SRR 1.43, 95% CI 1.15-1.78) were associated with thyroid cancer
      risk. Women that were in menopause at enrolment had a reduced thyroid cancer risk
      (SRR 0.79, 95% CI 0.62-1.01). No other menstrual, reproductive, and hormonal
      variable was associated with thyroid cancer risk. CONCLUSIONS: Menstrual and
      reproductive factors may play a role in the etiology of thyroid cancer, possibly
      through the mediation of estrogen receptors.

PMID- 25754112
TI  - Evaluation of various processes for simultaneous complexation and granulation to
      incorporate drug-cyclodextrin complexes into solid dosage forms.
AB  - Insoluble drugs often formulated with various excipients to enhance the
      dissolution. Cyclodextrins (CDs) are widely used excipients to improve
      dissolution profile of poorly soluble drugs. Drug-CD complexation process is
      complex and often requires multiple processes to produce solid dosage form.
      Hence, this study explored commonly used granulation processes for simultaneous
      complexation and granulation. Poorly soluble drugs ibuprofen and glyburide were
      selected as experimental drugs. Co-evaporation of drug:CD mixture from a solvent
      followed by wet granulation with water was considered as standard process for
      comparison. Spray granulation and fluid bed processing (FBP) using drug:CD
      solution in ethanol were evaluated as an alternative processes. The dissolution
      data of glyburide tablets indicated that tablets produced by spray granulation,
      FBP and co-evaporation-granulation have almost identical dissolution profile in
      water and 0.1% SLS (>70% in water and >60% in SLS versus 30 and 34%, respectively
      for plain tablet, in 120 min). Similarly, ibuprofen:CD tablets produced by co
      evaporation-granulation and FBP displayed similar dissolution profile in 0.01 M
      HCl (pH 2.0) and buffer pH 5.5 (>90 and 100% versus 44 and 80% respectively for
      plain tablets, 120 min). Results of this study demonstrated that spray
      granulation is simple and cost effective process for low dose poorly soluble
      drugs to incorporate drug:CD complex into solid dosage form, whereas FBP is
      suitable for poorly soluble drugs with moderate dose. 

PMID- 25754113
TI  - Adsorption and desorption characteristics of alcohol vapors on a nanoporous ZIF-8
      film investigated using silicon microcantilevers.
AB  - Zinc oxide nanorods were synthesized directly on a silicon microcantilever and
      converted into a nanoporous ZIF-8 film via a solvothermal reaction. The
      simultaneous measurements of the resonance frequency and deflection of the
      cantilever revealed that the adsorption of alcohol vapors induced a structural
      change in the ZIF-8 framework. 

PMID- 25754111
TI  - YAP1 Regulates OCT4 Activity and SOX2 Expression to Facilitate Self-Renewal and
      Vascular Mimicry of Stem-Like Cells.
AB  - Non-small cell lung cancer (NSCLC) is highly correlated with smoking and has very
      low survival rates. Multiple studies have shown that stem-like cells contribute
      to the genesis and progression of NSCLC. Our results show that the
      transcriptional coactivator yes-associated protein 1 (YAP1), which is the
      oncogenic component of the Hippo signaling pathway, is elevated in the stem-like
      cells from NSCLC and contributes to their self-renewal and ability to form
      angiogenic tubules. Inhibition of YAP1 by a small molecule or depletion of YAP1
      by siRNAs suppressed self-renewal and vascular mimicry of stem-like cells. These
      effects of YAP1 were mediated through the embryonic stem cell transcription
      factor, Sox2. YAP1 could transcriptionally induce Sox2 through a physical
      interaction with Oct4; Sox2 induction occurred independent of TEAD2 transcription
      factor, which is the predominant mediator of YAP1 functions. The binding of Oct4
      to YAP1 could be detected in cell lines as well as tumor tissues; the interaction
      was elevated in NSCLC samples compared to normal tissue as seen by proximity
      ligation assays. YAP1 bound to Oct4 through the WW domain, and a peptide
      corresponding to this region could disrupt the interaction. Delivery of the WW
      domain peptide to stem-like cells disrupted the interaction and abrogated Sox2
      expression, self-renewal, and vascular mimicry. Depleting YAP1 reduced the
      expression of multiple epithelial-mesenchymal transition genes and prevented the
      growth and metastasis of tumor xenografts in mice; overexpression of Sox2 in YAP1
      null cells rescued these functions. These results demonstrate a novel regulation
      of stem-like functions by YAP1, through the modulation of Sox2 expression.

PMID- 25754114
TI  - Interactions in hazard management policies: the case of drought in Nicaragua,
      1976-2010.
AB  - The literature on adaptive and multi-level governance calls for interactive
      hazard management to increase societies' resilience. This paper maps the hazard
      management policies in a poor and hazard-prone country-Nicaragua-and examines
      what role the government gives to interactions among different actors at
      different societal levels. A new analytical framework is developed that includes
      scope and direction to capture unidirectional or mutual interactions that are
      either horizontal or vertical. This enables a more complex analysis of
      interactions than that found in previous research. The review shows that the
      historical change in the role given to interactions, as a result of a focus on
      short-term emergency response being complemented by long-term risk management,
      mainly lies in how they are characterised-with more participants and other types
      of content categories-and the awareness that interactions other than mutual ones
      can be positive. This illustrates the complexity of the issue of interactions. 

PMID- 25754115
TI  - DdrO is an essential protein that regulates the radiation desiccation response
      and the apoptotic-like cell death in the radioresistant Deinococcus radiodurans
      bacterium.
AB  - Deinococcus radiodurans is known for its extreme radioresistance. Comparative
      genomics identified a radiation-desiccation response (RDR) regulon comprising
      genes that are highly induced after DNA damage and containing a conserved motif
      (RDRM) upstream of their coding region. We demonstrated that the RDRM sequence is
      involved in cis-regulation of the RDR gene ddrB in vivo. Using a transposon
      mutagenesis approach, we showed that, in addition to ddrO encoding a predicted
      RDR repressor and irrE encoding a positive regulator recently shown to cleave
      DdrO in Deinococcus deserti, two genes encoding alpha-keto-glutarate
      dehydrogenase subunits are involved in ddrB regulation. In wild-type cells, the
      DdrO cell concentration decreased transiently in an IrrE-dependent manner at
      early times after irradiation. Using a conditional gene inactivation system, we
      showed that DdrO depletion enhanced expression of three RDR proteins, consistent
      with the hypothesis that DdrO acts as a repressor of the RDR regulon. DdrO
      depleted cells loose viability and showed morphological changes evocative of an
      apoptotic-like response, including membrane blebbing, defects in cell division
      and DNA fragmentation. We propose that DNA repair and apoptotic-like death might
      be two responses mediated by the same regulators, IrrE and DdrO, but differently
      activated depending on the persistence of IrrE-dependent DdrO cleavage.

PMID- 25754116
TI  - Immunohistochemical- and PCR-based assay for the reproducible, routine detection
      of erythrovirus B19 in thyroid tissues.
AB  - It is generally accepted that thyroid follicle cells are at least semi-permissive
      for erythrovirus B19 (EVB19). Thus, various laboratory techniques have been
      successfully used to detect EVB19 in the thyroid gland, including polymerase
      chain reaction (PCR), immunohistochemistry, and in situ hybridization. However,
      the detection of EVB19 within the thyroid gland is problematic, and none of the
      detection protocols in the literature have been unequivocally validated. This
      multidisciplinary study in which 32 thyroidectomy subjects undergoing
      thyroidectomy in a French University hospital were prospectively recruited was
      performed over a period of 3 years. Prior to surgery, all the subjects were
      assayed for blood levels of anti-EVB19 antibodies and (using a quantitative PCR
      [qPCR] assay) EVB19 itself. A qPCR assay for EVB19 and an immunohistochemical
      assay (based on polyclonal anti-VP2 antibodies) were performed on the
      thyroidectomy samples. None of the subjects had an acute EVB19 infection. A viral
      load was detected in two serum samples and six thyroid biopsies. Three subjects
      had both a positive immunohistochemical assay and a positive qPCR assay for the
      thyroid tissue. It is noteworthy that the thyroid immunohistochemical and qPCR
      assays were negative in the two patients with detectable serum loads of EVB19. In
      conclusion, EVB19 can be detected in thyroid follicle cells by using
      immunohistochemical and qPCR assays. Ideally, patients should be tested with both
      PCR and immunohistochemical assays, in order to unequivocally confirm or rule out
      the presence of EVB19 in the thyroid gland. The present protocol must now be
      validated in larger series--notably with respect to its reliability and in order
      to determine qPCR positivity thresholds for application in future large-scale
      studies.

PMID- 25754118
TI  - Interleukin interrupted: a new strategy for the treatment of pancreatic cancer.

PMID- 25754117
TI  - Behavioral symptoms and sleep problems in children with anxiety disorder.
AB  - BACKGROUND: Sleep disorders are frequently associated with childhood behavioral
      problems and mental illnesses such as anxiety disorder. To identify promising
      behavioral targets for pediatric anxiety disorder therapy, we investigated the
      associations between specific sleep and behavioral problems. METHODS: We
      conducted retrospective reviews of 105 patients aged 4-12 years who met the DSM
      IV criteria for primary diagnosis of generalized anxiety disorder (n = 33),
      separation anxiety disorder (n = 23), social phobia (n = 21), or obsessive
      compulsive disorder (n = 28). Sleep problems were evaluated using the Children's
      Sleep Habits Questionnaire (CSHQ) and behavioral problems by the Spence
      Children's Anxiety Scale, Oppositional Defiant Behavior Inventory (ODBI), and
      Depression Self-Rating Scale for Children. RESULTS: Depressive behavior was
      weakly correlated with CSHQ subscores for sleep onset delay and night waking but
      not with total sleep disturbance. Anxiety was correlated with bedtime resistance,
      night waking, and total sleep disturbance score. Oppositional defiance was
      correlated with bedtime resistance, daytime sleepiness, sleep onset delay, and
      most strongly with total sleep disturbance. On multiple regression analysis ODBI
      score had the strongest positive association with total sleep disturbance and the
      strongest negative association with total sleep duration. CONCLUSIONS: Sleep
      problems in children with anxiety disorders are closely related to anxiety and
      oppositional defiant symptoms.

PMID- 25754119
TI  - The real thing: how to make human DC subsets.

PMID- 25754120
TI  - Reply to letter.

PMID- 25754121
TI  - Synthesis and characterization of tricarbastannatranes and their reactivity in
      B(C6F5)3-promoted conjugate additions.
AB  - The synthesis and characterization of a series of tricarbastannatranes, in the
      solid state and in solution, are described. The structures of the complexes
      [N(CH2 CH2 CH2 )3 Sn](BF4 ), [N(CH2 CH2 CH2 )3 Sn](SbF6 ), [N(CH2 CH2 CH2 )3 Sn]4
      [(SbF6 )3 Cl], and [(N(CH2 CH2 CH2 )3 Sn)2 OH][MeB(C6 F5 )3 ] were determined by
      X-ray crystallography. Furthermore, the B(C6 F5 )3 -promoted conjugate addition
      of alkyl-tricarbastannatranes to benzylidene derivatives of Meldrum's acid was
      investigated, and detailed mechanistic studies are presented. 

PMID- 25754122
TI  - Intravesical chitosan/interleukin-12 immunotherapy induces tumor-specific
      systemic immunity against murine bladder cancer.
AB  - Bladder cancer is a highly recurrent disease in need of novel, durable treatment
      strategies. This study assessed the ability of an intravesical immunotherapy
      composed of a coformulation of the biopolymer chitosan with interleukin-12 (CS/IL
      12) to induce systemic adaptive tumor-specific immunity. Intravesical CS/IL-12
      immunotherapy was used to treat established orthotopic MB49 and MBT-2 bladder
      tumors. All mice receiving intravesical CS/IL-12 immunotherapy experienced high
      cure rates of orthotopic disease. To investigate the durability and extent of the
      resultant adaptive immune response, cured mice were rechallenged both locally
      (intravesically) and distally. Cured mice rejected 100 % of intravesical tumor
      rechallenges and 50-100 % of distant subcutaneous rechallenges in a tumor
      specific manner. The ability of splenocytes from cured mice to lyse targets in a
      tumor-specific manner was assessed in vitro, revealing that lytic activity of
      splenocytes from cured mice was robust and tumor specific. Protective immunity
      was durable, lasting for at least 18 months after immunotherapy. In an advanced
      bladder cancer model, intravesical CS/IL-12 immunotherapy controlled simultaneous
      orthotopic and subcutaneous tumors in 70 % of treated mice. Intravesical CS/IL-12
      immunotherapy creates a robust and durable tumor-specific adaptive immune
      response against bladder cancer. The specificity, durability, and potential of
      this therapy to treat both superficial and advanced disease are deserving of
      consideration for clinical translation. 

PMID- 25754124
TI  - Improved formulas for the two optimum VFA flip-angles.

PMID- 25754123
TI  - CCL17 and CCL22/CCR4 signaling is a strong candidate for novel targeted therapy
      against nasal natural killer/T-cell lymphoma.
AB  - Nasal natural killer/T-cell lymphoma (NNKTL) is associated with Epstein-Barr
      virus and has a poor prognosis because of local invasion and/or multiple
      dissemination. Various chemokines play a role in tumor proliferation and
      invasion, and chemokine receptors including the C-C chemokine receptor 4 (CCR4)
      are recognized as potential targets for treating hematologic malignancies. The
      aim of the present study was to determine whether specific chemokines are
      produced by NNKTL. We compared chemokine expression patterns in culture
      supernatants of NNKTL cell lines with those of other lymphoma or leukemia cell
      lines using chemokine protein array and ELISA. Chemokine (C-C motif) ligand (CCL)
      17 and CCL22 were highly produced by NNKTL cell lines as compared to the other
      cell lines. In addition, CCL17 and CCL22 were readily observed in the sera of
      NNKTL patients. The levels of these chemokines were significantly higher in
      patients than in healthy controls. Furthermore, we detected the expression of
      CCR4 (the receptor for CCL17 and CCL22) on the surface of NNKTL cell lines and in
      tissues of NNKTL patients. Anti-CCR4 monoclonal antibody (mAb) efficiently
      induced antibody-dependent cellular cytotoxicity mediated by natural killer cells
      against NNKTL cell lines. Our results suggest that CCL17 and CCL22 may be
      important factors in the development of NNKTL and open up the possibility of
      immunotherapy of this lymphoma using anti-CCR4 mAb. 

PMID- 25754125
TI  - Critical evidence for the prediction error theory in associative learning.
AB  - In associative learning in mammals, it is widely accepted that the discrepancy,
      or error, between actual and predicted reward determines whether learning occurs.
      Complete evidence for the prediction error theory, however, has not been obtained
      in any learning systems: Prediction error theory stems from the finding of a
      blocking phenomenon, but blocking can also be accounted for by other theories,
      such as the attentional theory. We demonstrated blocking in classical
      conditioning in crickets and obtained evidence to reject the attentional theory.
      To obtain further evidence supporting the prediction error theory and rejecting
      alternative theories, we constructed a neural model to match the prediction error
      theory, by modifying our previous model of learning in crickets, and we tested a
      prediction from the model: the model predicts that pharmacological intervention
      of octopaminergic transmission during appetitive conditioning impairs learning
      but not formation of reward prediction itself, and it thus predicts no learning
      in subsequent training. We observed such an "auto-blocking", which could be
      accounted for by the prediction error theory but not by other competitive
      theories to account for blocking. This study unambiguously demonstrates validity
      of the prediction error theory in associative learning. 

PMID- 25754126
TI  - Detection of new human metabolic urinary markers in chronic alcoholism and their
      reversal by aqueous extract of Tinospora cordifolia stem.
AB  - AIMS: We have studied urine metabolic signature of chronic alcoholism (CA) before
      and after treatment with an Ayurvedic drug Tinospora cordifolia aqueous extract
      (TCE). METHODS: Urinary metabolites of chronic alcoholics and apparently healthy
      subjects were profiled using HPLC-Q-TOF-MS. Discrimination models from the
      initial data sets were able to correctly assign the unknown samples to the CA,
      treated or healthy groups in validation sets with r(2) > 0.98. RESULTS: Metabolic
      signature in CA patients include changed tryptophan, fatty acids and pyrimidines
      metabolism. Several novel biomarkers of alcoholism were observed in urine for the
      first time which includes, 5-hydroxyindole, phenylacetic acid, picolinic acid,
      quinaldic acid, histidine, cystathionine, riboflavin, tetrahydrobiopterin and
      chenodeoxyglycocholic acid, in addition to previously reported biomarkers.
      Treatment of CA with TCE reverted the levels of most of the biomarkers except
      tetrahydrobiopterin levels. CONCLUSIONS: These results suggested that the
      measurement of these urine metabolites could be used as a non-invasive diagnostic
      method for the detection of CA. As TCE treatment significantly reversed the
      affected pathways without any side effect. Overall, the present data depicts that
      TCE may be used either alone or adjunct in reducing alcohol-induced disorders.

PMID- 25754127
TI  - The relationship between population-level exposure to alcohol advertising on
      television and brand-specific consumption among underage youth in the US.
AB  - AIMS: We investigated the population-level relationship between exposure to brand
      specific advertising and brand-specific alcohol use among US youth. METHODS: We
      conducted an internet survey of a national sample of 1031 youth, ages 13-20, who
      had consumed alcohol in the past 30 days. We ascertained all of the alcohol
      brands respondents consumed in the past 30 days, as well as which of 20 popular
      television shows they had viewed during that time period. Using a negative
      binomial regression model, we examined the relationship between aggregated brand
      specific exposure to alcohol advertising on the 20 television shows [ad stock,
      measured in gross rating points (GRPs)] and youth brand-consumption prevalence,
      while controlling for the average price and overall market share of each brand.
      RESULTS: Brands with advertising exposure on the 20 television shows had a
      consumption prevalence about four times higher than brands not advertising on
      those shows. Brand-level advertising elasticity of demand varied by exposure
      level, with higher elasticity in the lower exposure range. The estimated
      advertising elasticity of 0.63 in the lower exposure range indicates that for
      each 1% increase in advertising exposure, a brand's youth consumption prevalence
      increases by 0.63%. CONCLUSIONS: At the population level, underage youths'
      exposure to brand-specific advertising was a significant predictor of the
      consumption prevalence of that brand, independent of each brand's price and
      overall market share. The non-linearity of the observed relationship suggests
      that youth advertising exposure may need to be lowered substantially in order to
      decrease consumption of the most heavily advertised brands.

PMID- 25754129
TI  - Enediyne dimerization vs Bergman cyclization.
AB  - High-level quantum chemical calculations reveal that the dimerization of
      enediynes to 1,3-butadiene-1,4-diyl diradicals is energetically more favored than
      the corresponding Bergman cyclization of enediynes. Moreover, the activation
      barrier of both reactions can be drastically reduced by the introduction of
      electron-withdrawing substituents like fluoro groups at the reacting carbon
      centers of the triple bonds. 

PMID- 25754128
TI  - [New methods of diagnosis in tuberculosis].
AB  - Bacteriological diagnosis of tuberculosis has benefited in recent years from many
      technological advances to improve rapidity and sensitivity of the techniques.
      Thus, new LED fluorescence microscopes are in the process of replacing the
      optical microscopes and the Ziehl-Neelsen technique, making the examination more
      precise, faster and easier. The manual and automatic liquid culture has improved
      Lowenstein-Jensen culture and helped shorten antibiotic sensitivity test,
      allowing appropriate management of patients. The development and standardization
      of molecular biology methods led to the rapid detection and identification of
      mycobacterium directly in clinical samples but also of resistance genes for early
      diagnosis of MDR-TB and dealing with them quickly. However, the performance of
      these techniques does not sufficiently cover the diagnosis of smear-negative
      tuberculosis, extrapulmonary forms, children- and immune-compromised tuberculosis
      where sensitivity is limited. The diagnosis of latent tuberculosis is reinforced
      by the in vitro release testing of gamma interferon overcoming the lack of
      specificity of the tuberculin skin test. Despite considerable progress, more
      amelioration is still needed to improve these techniques in order to extend them
      to the paucibacillary tuberculosis and to facilitate their access to low-resource
      countries. 

PMID- 25754130
TI  - Pleomorphism during Ventricular Tachycardia: A Distinguishing Feature between
      Cardiac Sarcoidosis and Idiopathic VT.
AB  - BACKGROUND: Ventricular tachycardia (VT), a common manifestation of cardiac
      sarcoidosis (CS), is associated with high morbidity and mortality. It could be
      mistaken for idiopathic VT (IVT) in the absence of systemic manifestations and
      overt cardiac structural abnormality. We studied the electrocardiogram (ECG)
      characteristics of VT in CS that may distinguish from IVT and also explored the
      relationship of the ECG characteristics with imaging findings in patients with
      CS. METHODS AND RESULTS: Twelve-lead ECG characteristics of VT in CS patients
      (Group I = 37) were compared with IVT (Group II = 49). QRS duration, axis,
      morphology, VT cycle length, and cycle length variation (CLV) were analyzed. In
      Group I, 18 (49%) had pleomorphic VT (PLVT) and none in Group II. CLV was seen
      only in Group I (24%). Mean QRS duration (milliseconds) and cycle length
      (milliseconds) were greater in Group I (QRSd 152.49 [39.3] vs 140.9 [19.2]) and
      (332.2 [136.5] vs 312.9 [56.2]), the differences not statistically significant.
      In Group I, myocardial scar was present in 22 of 25 patients and myocardial
      inflammation in 28 of 29 patients as assessed by cardiac magnetic resonance
      imaging (delayed enhancement) and 18-fluorodeoxyglucose positron emission
      computed tomography, respectively. PLVT was seen more commonly in patients with
      involvement of >1 myocardial region than focal involvement (58% and 30%,
      respectively, with myocardial scar and 50% and 40%, respectively, with myocardial
      inflammation). CONCLUSION: Pleomorphism and CLV during VT may be distinguishing
      features between IVT and VTs of CS origin.

PMID- 25754131
TI  - G-Protein-Coupled Chemokine Receptor Gene in Lumpy Skin Disease Virus Isolates
      from Cattle and Water Buffalo (Bubalus bubalis) in Egypt.
AB  - Lumpy skin disease virus (LSDV), sheep poxvirus (SPV) and goat poxvirus (GPV) are
      the most serious poxviruses of ruminants. In this study, we analysed the G
      protein-coupled chemokine receptor (GPCR) genes of LSDV isolates from cattle and
      water buffalo (Bubalus bubalis) in Egypt during the summer of 2011. Multiple
      alignments of the nucleotide sequences revealed that the water buffalo LSDV
      isolate differed from the cattle isolate at four nucleotide positions, and both
      isolates had nine nucleotide mutations from the reference strain, Egyptian tissue
      culture-adapted cattle LSDV/Ismailyia88 strain. Compared with the GPCR sequences
      of SPV and GPV strains, a 21 nucleotide insertion and a 12 nucleotide deletion
      were identified in the GPCR genes of our used isolates and other LSDVs. The amino
      acid sequences of GPCR genes of our isolates contained the unique signature of
      LSDV (A11 , T12 , T34 , S99 and P199 ). Phylogenetic analyses showed that the
      GPCR genes of cattle and water buffalo LSDVs were closest genetically, indicating
      a potential transmission of cattle LSDV to water buffalo.

PMID- 25754132
TI  - Access Barriers to Dental Health Care in Children with Disability. A
      Questionnaire Study of Parents.
AB  - BACKGROUND: A patient's with disability everyday life is rife with many
      limitations such as architectural, transport, information as well as medical,
      psychological, legal, economic and social barriers. The aim of this study was to
      evaluate access to dental health care of special-care schoolchildren with
      intellectual disability on the basis of their parents' opinion. MATERIAL AND
      METHOD: A questionnaire survey was carried out among 264 parents/caregivers of
      children from eight special-care schools in Poznan (Poland). Close-ended
      questions concerned children's barriers in access to dental care and parents'
      satisfaction with their children's dental care. RESULTS: Only 31.8%
      parents/caregivers did not have any problems with access to dental care and the
      most commonly reported barrier to obtaining dental care was protracted waiting
      time for a visit (36.7%). Most commonly, children were treated in dental surgery
      conditions (90.1%). Only 42.1% respondents were satisfied with their children's
      dental care. CONCLUSIONS: The research revealed that there is a need to improve
      the access of children with disability to dental care. Hence, it seems to be
      beneficial to set up specialist dental surgeries in special-care schools which
      would improve the access of children with disability to prophylaxis as well as
      dental treatment.

PMID- 25754134
TI  - Erratum to: Unique hues as revealed by unique-hue selecting versus partial hue
      matching.

PMID- 25754133
TI  - Mental illness and parenthood: being a parent in secure psychiatric care.
AB  - BACKGROUND: Research into parenting and mental illness seldom includes forensic
      mental health service users, despite its relevance to therapeutic, family work
      and risk management. AIMS: This study aimed to understand the experiences of
      parents and the variety of parenting roles maintained during admission to a
      secure forensic hospital. METHODS: Narrative interviews with 18 parents (eight
      mothers and 10 fathers) at an English medium security hospital were analysed
      thematically, using the framework approach. The proportion of patients who are
      parents and their contact patterns with their children were estimated from
      records. RESULTS: About a quarter of men and 38% of women were parents.
      Parenthood was of central importance to their emotional life, spanning
      experiences of loss, shame and failed expectations, joy, responsibility and hope.
      Fewer fathers maintained contact with their children than mothers yet fatherhood
      remained a vital aspect of men's identities, with impact on their self-esteem.
      Parenting during lengthy admissions--while constrained and dependent on
      professional support and surveillance--ranged from sending gifts and money to
      visits and phone calls. Offending was seen as a particularly shameful aspect of
      admission, contributing to distancing from the children and difficulty explaining
      detention to them. CONCLUSIONS: Such complex experiences call for
      multidisciplinary knowledge and skills. Provision of focused therapy, as well as
      appropriate visiting spaces, creative approaches to contact time and support for
      patients in explaining their mental illness and detention to their children are
      recommended.

PMID- 25754135
TI  - A QM-MD simulation approach to the analysis of FRET processes in (bio)molecular
      systems. A case study: complexes of E. coli purine nucleoside phosphorylase and
      its mutants with formycin A.
AB  - Predicting FRET pathways in proteins using computer simulation techniques is very
      important for reliable interpretation of experimental data. A novel and
      relatively simple methodology has been developed and applied to purine nucleoside
      phosphorylase (PNP) complexed with a fluorescent ligand - formycin A (FA). FRET
      occurs between an excited Tyr residue (D*) and FA (A). This study aims to
      interpret experimental data that, among others, suggests the absence of FRET for
      the PNPF159A mutant in complex with FA, based on novel theoretical methodology.
      MD simulations for the protein molecule containing D*, and complexed with A, are
      carried out. Interactions of D* with its molecular environment are accounted by
      including changes of the ESP charges in S1, compared to S0, and computed at the
      SCF-CI level. FRET probability W F depends on the inverse six-power of the D*-A
      distance, R da . The orientational factor 0 < k(2) < 4 between D* and A is
      computed and included in the analysis. Finally W F is time-averaged over the MD
      trajectories resulting in its mean value. The red-shift of the tyrosinate anion
      emission and thus lack of spectral overlap integral and thermal energy
      dissipation are the reasons for the FRET absence in the studied mutants at pH 7
      and above. The presence of the tyrosinate anion results in a competitive energy
      dissipation channel and red-shifted emission, thus in consequence in the absence
      of FRET. These studies also indicate an important role of the phenyl ring of
      Phe159 for FRET in the wild-type PNP, which does not exist in the Ala159 mutant,
      and for the effective association of PNP with FA. In a more general context, our
      observations point out very interesting and biologically important properties of
      the tyrosine residue in its excited state, which may undergo spontaneous
      deprotonation in the biomolecular systems, resulting further in unexpected
      physical and/or biological phenomena. Until now, this observation has not been
      widely discussed in the literature.

PMID- 25754136
TI  - The electronic mechanism ruling the dihydrogen bonds and halogen bonds in weakly
      bound systems of H3SiH...HOX and H 3SiH...XOH (X = F, Cl, and Br).
AB  - The dihydrogen bond complexes (H3SiH???HOX) and halogen bond complexes
      (H3SiH???XOH) formed between SiH4 and hypohalous acids HOX (X = F, Cl, and Br)
      have been studied at the MP2/6-311++G(2d,2p) computational level. The analyses of
      structure and infrared vibration frequencies have revealed tendencies in the red
      shifts and blue shifts of the stretch frequencies of the Si-H, H-O, and O-X
      bonds. Besides the computation of the interaction energies, punctual atomic
      charges and charge transference amounts were determined at light of the Natural
      Bond Orbital (NBO) approach, by which the quantifications of the s- and p
      characters of hydrogen, oxygen, and silicon also were useful to unveil the
      frequency shifts aforementioned. With the purpose to elucidate the donor/acceptor
      interface along the charge transfer mechanism between the dihydrogen bonds and
      halogen bonds, the application of the hierarchical cluster analysis (HCA) and
      principal component analysis (PCA) chemometric techniques were useful in this
      regard. Moreover, the interaction strengths of the H3SiH???HOX and H3SiH???XOH
      complexes was computed through a model that embodies the frequency shifts and
      topological parameters derived from quantum theory of atoms in molecules (QTAIM).

PMID- 25754137
TI  - Molecular dynamics study of the inhibitory effects of ChEMBL474807 on the enzymes
      GSK-3beta and CDK-2.
AB  - Indirubin derivatives and analogs comprise a significant group of ATP-competitive
      inhibitors. The inhibitory effects of ChEMBL474807 (1-(4-amino-1,2,5-oxadiazol-3
      yl)-5-(piperidin-1-ylmethyl)-N'-(pyridin-4-ylmethylene)-1H-1,2,3-triazole-4
      carbohydrazide) on two enzymes, namely glycogen synthase kinase-3beta (GSK-3beta)
      and cyclin-dependent kinase-2 (CDK-2), were analyzed. The close resemblance of
      the amino acid sequences of these two enzymes (with 25% identity and 41%
      similarity) explains why indirubin derivatives are inhibitors of both of the
      enzymes studied. The docking and molecular dynamics investigation performed here
      led to the identification of the interactions responsible for stabilizing the
      ligand ChEMBL474807 at the active sites of the enzymes considered. The structural
      and energetic data collected during our investigations clearly indicate that
      there are important differences in the behavior of the ligand at the two active
      sites investigated here.

PMID- 25754138
TI  - Insight into the substitution reactions of silylenoid H2SiLiF with GeH3X (X = F,
      Cl, Br): a theoretical study.
AB  - The unique substitution reactions of the three-membered-ring silylenoid H2SiLiF
      with GeH3X (X = F, Cl, Br) were investigated using ab initio and density
      functional theory calculations. All stationary points on the potential energy
      surfaces were optimized at the B3LYP/6-311 + G (d, p) level of theory and the
      QCISD method was then used to calculate the single-point energies. Theoretical
      calculations predicted that the substitution reactions of H2SiLiF with GeH3X
      proceed via two reaction paths (I and II), while forming the same product H2FSi
      GeH3. In either pathway, there is one precursor complex (Q), one transition state
      (TS), and one intermediate (IM) connecting the reactants and products. The
      substitution reaction barriers of H2SiLiF with GeH3X for path I (48.49, 42.71,
      and 38.71 kJ mol(-1)) decreased with the increase for the same-family element X
      from up to down in the periodic table, whereas the substitution barriers for path
      II (6.51, 22.04, and 23.62 kJ mol(-1)) increased with the increase in atomic
      number of X (X = F, Cl, Br). Path II was more favorable than path I. All the
      substitution reactions of H2SiLiF with GeH3X were exothermic. The elucidation of
      the unique mechanism of these substitution reactions suggests a new reaction mode
      of silicon-germanium bond formation. 

PMID- 25754139
TI  - Reproducibility of automated volumetric breast density assessment in short-term
      digital mammography reimaging.
AB  - Two automated volumetric breast density analyses of 44 patients who underwent
      image-guided needle localization in one breast were compared to calculate the
      agreement of assessment parameters in short-term digital mammography reimaging.
      The outputs of the automated volumetric breast density method included four
      parameters [fibroglandular tissue volume (Vfg), total breast volume (Vb),
      volumetric breast density (Vbd), and area breast density (Abd)]. The variability
      and agreement of each parameter were calculated in serial mammograms. There was
      no significant difference in mean Vfg, Vb, Vbd, or Abd between two mammograms (P
      = .249, .053, .727, and .603, respectively). 

PMID- 25754140
TI  - Prostate cancer recurrence manifesting as superior vena cava syndrome.

PMID- 25754141
TI  - A new surgical technique of hymenoplasty.
AB  - OBJECTIVE: To review data from patients who have undergone hymenoplasty with a
      novel surgical technique, termed the STSI (suture three stratums around the
      introitus) method. METHODS: In a retrospective study, data were reviewed from
      patients who underwent hymenoplasty by STSI at a center in Beijing, China,
      between January 2010 and January 2014. Patients were scheduled to attend a follow
      up appointment 1 month after surgery. Long-term follow-up was conducted by
      telephone. Follow-up data and preoperative and postoperative photos were
      assessed. RESULTS: Overall, 125 patients had undergone hymenoplasty using the
      STSI method. Only 1 (0.8%) patient had an early postoperative complication
      (uncontrolled bleeding). Among the 99 patients who returned for follow-up at 1
      month, healing was recorded for 91 (91.9%). Long-term follow-up suggested that no
      patient had persistent dyspareunia, menstruation changes, or other health
      problems after the surgery. Among 51 patients who reported sexual intercourse
      since the surgery, 47 (92.2%) were satisfied with the outcome and 28 (54.9%)
      reported blood loss during the first intercourse. CONCLUSION: The STSI method
      seems to be an effective, enduring, and safe technique of hymenoplasty.

PMID- 25754142
TI  - Clinical features of fallopian tube accessory ostium and outcomes after
      laparoscopic treatment.
AB  - OBJECTIVE: To investigate the clinical features of fallopian tube accessory
      ostium and treatment outcomes after laparoscopic treatment. METHODS: A
      retrospective analysis was conducted of patients who underwent laparoscopy for
      infertility at Peking University People's Hospital, Beijing, China, between June
      1, 2009, and January 31, 2012. Fallopian tube accessory ostium was treated
      surgically when identified. Other procedures were conducted simultaneously, if
      indicated. Patients were interviewed by telephone every 6 months after treatment.
      RESULTS: Among 1113 patients who underwent laparoscopy for infertility, 21 (1.9%)
      were diagnosed with fallopian tube accessory ostium. Furthermore, 19 (90.5%) of
      these 21 women were diagnosed with pelvic endometriosis. Accessory ostium was
      identified in 19 (4.7%) of 403 women with endometriosis versus 2 (0.3%) of 710
      women without endometriosis (P=0.001). Among 18 patients with accessory ostium
      who completed follow-up and wished to conceive, 12 (66.7%) conceived after
      surgery, one of whom experienced a spontaneous abortion. No ectopic pregnancies
      occurred. CONCLUSION: Accessory ostium was confirmed by a thorough examination of
      the entire fallopian tube, especially the distal portion, during laparoscopy.
      Patients experienced satisfactory outcomes after surgical intervention.

PMID- 25754143
TI  - Medical, legal, and ethical challenges associated with pregnancy and catastrophic
      brain injury.
AB  - In late 2013, two women from North America gained attention after sustaining
      catastrophic brain injuries while pregnant. After Marlise Munoz--who was at 14
      weeks of pregnancy when she developed a pulmonary embolism--was pronounced brain
      dead, hospital officials initially refused to withdraw support, citing a Texas
      state law requiring them to maintain life-sustaining treatment for a pregnant
      patient to help to save the fetus. By contrast, when Robyn Benson was pronounced
      brain dead after a brain hemorrhage at 22 weeks of pregnancy, both her husband
      and the physicians agreed to continue support until a viable child could be
      delivered. The Munoz and Benson cases offer an opportunity to explore the
      medical, legal, and ethical issues surrounding catastrophic brain injury in
      pregnant women. It is hoped that the present article will enable clinicians to
      better appreciate the history and present state of issues involving advance
      directives for pregnant women, maternal versus fetal interests, and the impact of
      fetal viability on medical decision making, as well as offer a practical
      assessment of the various US state laws concerning the rare, yet catastrophic
      event of brain injury in a pregnant woman.

PMID- 25754144
TI  - Aplasia cutis congenita presenting as vacuum-extractor-related trauma.

PMID- 25754145
TI  - Contribution of NMDA receptors to dorsolateral prefrontal cortical networks in
      primates.
AB  - Cognitive disorders such as schizophrenia and Alzheimer's disease are associated
      with dysfunction of the highly evolved dorsolateral prefrontal cortex (dlPFC),
      and with changes in glutamatergic N-methyl-D-aspartate receptors (NMDARs). Recent
      research on the primate dlPFC discovered that the pyramidal cell circuits that
      generate the persistent firing underlying spatial working memory communicate
      through synapses on spines containing NMDARs with NR2B subunits (GluN2B) in the
      post-synaptic density. This contrasts with synapses in the hippocampus and
      primary visual cortex, where GluN2B receptors are both synaptic and
      extrasynaptic. Blockade of GluN2B in the dlPFC markedly reduces the persistent
      firing of the Delay cells needed for neuronal representations of visual space.
      Cholinergic stimulation of nicotinic alpha7 receptors within the glutamate
      synapse is necessary for NMDAR actions. In contrast, alpha-amino-3-hydroxy-5
      methyl-4-isoxazolepropionic acid receptors have only subtle effects on the
      persistent firing of Delay cells, but contribute substantially to the firing of
      Cue and Response cells. Systemic administration of the NMDAR antagonist ketamine
      reduces the persistent firing of Delay cells, but increases the firing of some
      Response cells. The reduction in persistent firing produced by ketamine may
      explain why this drug can mimic or worsen the cognitive symptoms of
      schizophrenia. Similar actions in the medial PFC circuits representing the
      emotional aspects of pain may contribute to the rapid analgesic and anti
      depressant actions of ketamine. 

PMID- 25754146
TI  - Effects of testosterone and estradiol on anxiety and depressive-like behavior via
      a non-genomic pathway.
AB  - Besides their known slow genomic effects, testosterone and estradiol have rapid
      effects in the brain. However, their impact on mood-related behavior is not
      clear. The aim of this study was to investigate the non-genomic pathway of
      testosterone and estradiol in the amygdala in relation to anxiety and depressive
      like behavior. Sham-operated and gonadectomized male rats (GDX) supplemented with
      testosterone propionate, estradiol, or olive oil were used. Five minutes after
      administration, anxiety and depression-like behavior were tested. Estradiol
      increased anxiolytic behavior in the open-field test compared to the GDX group,
      but administration of testosterone had no significant effect. Besides, c-Fos
      expression in the medial nucleus of the amygdala significantly increased after
      testosterone treatment compared to the GDX group, while no significant difference
      was observed in the central and the basolateral nuclei of the amygdala in the
      testosterone-treated group compared to the GDX group. In conclusion, estradiol
      had an anxiolytic effect via a rapid pathway, but no rapid effect of testosterone
      on anxiety was found. Further studies elucidating whether the rapid effect is
      mediated by a non-genomic pathway are needed. 

PMID- 25754147
TI  - Dose-dependent regulation of oligodendrocyte specification by beta-catenin
      signaling.

PMID- 25754148
TI  - Novel flavours paired with glutamate condition increased intake in older adults
      in the absence of changes in liking.
AB  - Previous research on the repeat exposure to a novel flavour combined with
      monosodium glutamate (MSG) has shown an increase in liking and consumption for
      the particular flavour. The aim of the current work was to investigate whether
      this could also be observed in the case of older people, since they are most
      affected by undernutrition in the developed world and ways to increase
      consumption of food are of significant importance for this particular age group.
      For this study, 40 older adults (age 65-88) repeatedly consumed potato soup with
      two novel flavours (lemongrass and cumin) which were either with or without a
      high level of MSG (5% w/w). A randomized single blind within-subject design was
      implemented, where each participant was exposed to both soup flavours three times
      over 6 days, with one of the soup flavours containing MSG. After three repeat
      exposures, consumption increased significantly for the soups where the flavours
      had contained MSG during the repeated exposure (mean weight consumed increased
      from 123 to 164 g, p = 0.017), implying that glutamate conditioned for increased
      wanting and consumption, despite the fact that the liking for the soup had not
      increased.

PMID- 25556369
TI  - 14-3-3zeta regulates immune response through Stat3 signaling in oral squamous
      cell carcinoma.
AB  - Ectopic expression of 14-3-3zeta has been found in various malignancies,
      including lung cancer, liver cancer, head and neck squamous cell carcinoma
      (HNSCC), and so on. However, the effect of 14-3-3zeta in the regulation of
      interactions between tumor cells and the immune system has not been previously
      reported. In this study, we aimed to investigate whether and how 14-3-3zeta is
      implicated in tumor inflammation modulation and immune recognition evasion. In
      oral squamous cell carcinoma (OSCC) cell lines and cancer tissues, we found that
      14-3-3zeta is overexpressed. In OSCC cells, 14-3-3zeta knockdown resulted in the
      up-regulated expression of inflammatory cytokines. In contrast, 14-3-3zeta
      introduction attenuated cytokine expression in human normal keratinocytes and
      fibroblasts stimulated with interferon-gamma (IFN-gamma) and lipopolysaccharide
      (LPS). Furthermore, supernatants from 14-3-3zeta knockdown OSCC cells
      dramatically altered the response of peritoneal macrophages, dendritic cells and
      tumor-specific T cells. Interestingly, Stat3 was found to directly interact with
      14-3-3zeta and its disruption relieved the inhibition induced by 14-3-3zeta in
      tumor inflammation. Taken together, our studies provide evidence that 14-3-3zeta
      may regulate tumor inflammation and immune response through Stat3 signaling in
      OSCC. 

PMID- 25754154
TI  - Increased risk after noninvasive prenatal screening on cell-free DNA circulating
      in maternal blood: does a new indication for invasive prenatal diagnosis require
      new criteria for confirmatory cytogenetic analysis?

PMID- 25754160
TI  - Successful Interferon-Free Therapy of Chronic Hepatitis C Virus Infection
      Normalizes Natural Killer Cell Function.
AB  - BACKGROUND & AIMS: Chronic hepatitis C virus infection activates an intrahepatic
      immune response, leading to increased expression of interferon (IFN)-stimulated
      genes and activation of natural killer (NK) cells-the most prevalent innate
      immune cell in the liver. We investigated whether the elimination of hepatitis C
      virus with direct-acting antiviral normalizes expression of IFN-stimulated genes
      and NK cell function. METHODS: We used multicolor flow cytometry to analyze NK
      cells from the liver and blood of 13 HCV-infected patients who did not respond to
      treatment with pegylated interferon and ribavirin. Samples were collected before
      and during IFN-free treatment with daclatasvir and asunaprevir and compared with
      samples from the blood of 13 healthy individuals (controls). Serum levels of
      chemokine C-X-C motif ligand (CXCL) 10 or CXCL11 were measured by enzyme-linked
      immunosorbent assay. RESULTS: Before treatment, all patients had increased levels
      of CXCL10 or CXCL11 and a different NK cell phenotype from controls,
      characterized by increased expression of HLA-DR, NKp46, NKG2A, CD85j, signal
      transducer and activator of transcription 1 (STAT1), phosphorylated STAT1, and
      tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). NK cells from
      patients also had increased degranulation and decreased production of IFNgamma
      and tumor necrosis factor alpha compared with NK cells from controls. Nine
      patients had an end-of-treatment response (undetectable virus) and 4 had
      virologic breakthrough between weeks 4 and 12 of therapy. A rapid decrease in
      viremia and level of inflammatory cytokines in all patients was associated with
      decreased activation of intrahepatic and blood NK cells; it was followed by
      restoration of a normal NK cell phenotype and function by week 8 in patients with
      undetectable viremia. This normalized NK cell phenotype was maintained until week
      24 (end of treatment). CONCLUSIONS: Direct-acting antiviral-mediated clearance of
      HCV is associated with loss of intrahepatic immune activation by IFNalpha, which
      is indicated by decreased levels of CXCL10 and CXCL11 and normalization of NK
      cell phenotype and function.

PMID- 25754161
TI  - Vascular endothelial growth factor C disrupts the endothelial lymphatic barrier
      to promote colorectal cancer invasion.
AB  - BACKGROUND & AIMS: Colorectal cancer (CRC) is highly metastatic. Metastases
      spread directly into local tissue or invade distant organs via blood and
      lymphatic vessels, but the role of lymphangiogenesis in CRC progression has not
      been determined. Lymphangiogenesis is induced via vascular endothelial growth
      factor C (VEGFC) activation of its receptor, VEGFR3; high levels of VEGFC have
      been measured in colorectal tumors undergoing lymphangiogenesis and correlated
      with metastasis. We investigated VEGFC signaling and lymphatic barriers in human
      tumor tissues and mice with orthotopic colorectal tumors. METHODS: We performed
      immunohistochemical, immunoblot, and real-time polymerase chain reaction analyses
      of colorectal tumor specimens collected from patients; healthy intestinal tissues
      collected during operations of patients without CRC were used as controls. CT26
      CRC cells were injected into the distal posterior rectum of BALB/c-nude mice.
      Mice were given injections of an antibody against VEGFR3 or an adenovirus
      encoding human VEGFC before orthotopic tumors and metastases formed. Lymph node,
      lung, and liver tissues were collected and evaluated by flow cytometry. We
      measured expression of vascular endothelial cadherin (CDH5) on lymphatic vessels
      in mice and in human intestinal lymphatic endothelial cells. RESULTS: Levels of
      podoplanin (a marker of lymphatic vessels), VEGFC, and VEGFR3 were increased in
      colorectal tumor tissues, compared with controls. Mice that expressed VEGFC from
      the adenoviral vector had increased lymphatic vessel density and more metastases
      in lymph nodes, lungs, and livers, compared with control mice. Anti-VEGFR3
      antibody reduced numbers of lymphatic vessels in colons and prevented metastasis.
      Expression of VEGFC compromised the lymphatic endothelial barrier in mice and
      endothelial cells, reducing expression of CDH5, increasing permeability, and
      increasing trans-endothelial migration by CRC cells. Opposite effects were
      observed in mice and cells when VEGFR3 was blocked. CONCLUSIONS: VEGFC signaling
      via VEGFR3 promotes lymphangiogenesis and metastasis by orthotopic colorectal
      tumors in mice and reduces lymphatic endothelial barrier integrity. Levels of
      VEGFC and markers of lymphatic vessels are increased in CRC tissues from
      patients, compared with healthy intestine. Strategies to block VEGFR3 might be
      developed to prevent CRC metastasis in patients.

PMID- 25754162
TI  - Analysis of clinical efficacy, side effects, and laboratory changes among
      patients with acne vulgaris receiving single versus twice daily dose of oral
      isotretinoin.
AB  - Acne vulgaris is a debilitating disorder and requires proper treatment. This work
      evaluates the clinical efficacy, side effects, and laboratory changes of serum
      lipids and liver function during oral isotretinoin therapy for acne vulgaris,
      comparing single versus twice daily dose. Fifty-eight patients with acne vulgaris
      were included and randomized into group I (26 patients), who received once daily
      dose, and group II (32 patients), who received twice daily dose of oral
      isotretinoin. Global acne scoring system was used to evaluate acne severity and
      post-treatment improvement. Both regimens resulted in highly significant clinical
      improvement of acne with no significant difference. However, side effects were
      significantly more common among patients of group I. Both regimens caused mild
      rise of serum cholesterol, alanine transaminase (ALT), and aspartate
      aminotransferase (AST) with more prominent rise of triglycerides especially with
      twice daily dose. Oral isotretinoin is a very effective treatment for acne
      vulgaris with no statistically significant difference in clinical efficacy
      between once and twice daily doses. However, dividing dose to twice per day might
      cause fewer incidence of side effects without reducing clinical efficacy. The
      drug causes mild clinically insignificant rise of serum cholesterol,
      triglycerides, AST, and ALT. 

PMID- 25754163
TI  - Recurrent ischaemic stroke unveils polycythaemia vera.
AB  - Polycythaemia vera is a recognised cause of ischaemic stroke. If not treated,
      this condition may result in recurrent strokes. This is a case of a 61-year-old
      Caucasian man presenting with the inability to ambulate for 3 days. Brain imaging
      revealed acute and chronic infarctions in the brain stem and the cerebrum.
      Polycythaemia vera was diagnosed and treated during the admission. The unique
      mechanisms and management issues of ischaemic stroke associated with
      polycythaemia vera are discussed.

PMID- 25754164
TI  - An unusual cause of neonatal cyanosis....
AB  - We report a case of a female neonate whose pulse oximetry screening for
      congenital heart disease at 40 h of life was positive. The pregnancy was
      uneventful with no relevant family history. The neonate presented with bluish
      discolouration of the skin lasting until day 15. Cardiovascular examination and
      chest radiography were normal. Septic screening was negative. Oxygen therapy was
      started with poor response; investigations revealed a methaemoglobinaemia of
      7.4%. The methaemoglobin level reached a peak of 15% on day 10, falling
      thereafter. The infant was discharged by day 20 with a normal physical
      examination and a methaemoglobinaemia of 11.4%. By 2 months of age this had
      fallen to 2.4%. Further investigation revealed a haemoglobin M variant: a
      heterozygous mutation of the gamma globin gene known as Hb F-M Viseu. The
      mutation occurs in the gamma chain, therefore the methaemoglobinaemia is
      transitory, resolving with the transition from fetal to adult haemoglobin.

PMID- 25754159
TI  - Features and Outcomes of 899 Patients With Drug-Induced Liver Injury: The DILIN
      Prospective Study.
AB  - BACKGROUND & AIMS: The Drug-Induced Liver Injury Network is conducting a
      prospective study of patients with DILI in the United States. We present
      characteristics and subgroup analyses from the first 1257 patients enrolled in
      the study. METHODS: In an observational longitudinal study, we began collecting
      data on eligible individuals with suspected DILI in 2004, following them for 6
      months or longer. Subjects were evaluated systematically for other etiologies,
      causes, and severity of DILI. RESULTS: Among 1257 enrolled subjects with
      suspected DILI, the causality was assessed in 1091 patients, and 899 were
      considered to have definite, highly likely, or probable DILI. Ten percent of
      patients died or underwent liver transplantation, and 17% had chronic liver
      injury. In the 89 patients (10%) with pre-existing liver disease, DILI appeared
      to be more severe than in those without (difference not statistically
      significant; P = .09) and mortality was significantly higher (16% vs 5.2%; P <
      .001). Azithromycin was the implicated agent in a higher proportion of patients
      with pre-existing liver disease compared with those without liver disease (6.7%
      vs 1.5%; P = .006). Forty-one cases with latency <=7 days were caused
      predominantly by antimicrobial agents (71%). Two most common causes for 60 DILI
      cases with latency >365 days were nitrofurantoin (25%) or minocycline (17%).
      There were no differences in outcomes of patients with short vs long latency of
      DILI. Compared with individuals younger than 65 years, individuals 65 years or
      older (n = 149) were more likely to have cholestatic injury, although mortality
      and rate of liver transplantation did not differ. Nine patients (1%) had
      concomitant severe skin reactions; implicated agents were lamotrigine,
      azithromycin, carbamazepine, moxifloxacin, cephalexin, diclofenac, and
      nitrofurantoin. Four of these patients died. CONCLUSIONS: Mortality from DILI is
      significantly higher in individuals with pre-existing liver disease or
      concomitant severe skin reactions compared with patients without. Additional
      studies are needed to confirm the association between azithromycin and increased
      DILI in patients with chronic liver disease. Older age and short or long
      latencies are not associated with DILI mortality.

PMID- 25754165
TI  - Cerebrospinal fluid involvement in acute promyelocytic leukaemia at presentation.
AB  - In acute promyelocytic leukaemia (APL), extramedullary disease (EMD) is rare but
      can occur in those who relapse following therapy. Although the most common site
      of EMD in APL is central nervous system (CNS) and skin, CNS involvement in
      recently diagnosed patients with APL is very rare and rarely described. We report
      cerebrospinal fluid involvement in a case of APL, on day 3 of induction therapy. 

PMID- 25754166
TI  - Complete atrioventricular block in pregnancy: report of seven pregnancies in a
      patient without pacemaker.
AB  - Obstetric management of a woman with a permanent pacemaker in situ is well
      reported in the literature; but those who present without pacing are still
      debatable. The necessity for setting the optimal timing or rate of temporary
      artificial pacing, specifically for labour, has not been objectively assessed.
      Temporary pacing in most cases reported in the literature might be to withstand
      the variations in haemodynamic status during delivery and labour. We report a
      case of a patient with complete heart block without any pacing who had seven
      pregnancies without any significant changes in haemodynamic status during labour
      and delivery. Managing a pregnancy without pacing might be an appropriate
      alternative for women without any underlying cardiac disorder, as it will not
      lead to significant changes in the haemodynamic system. 

PMID- 25754167
TI  - A difficult diagnosis: severe Graves' ophthalmolopathy.
AB  - An 81-year-old woman with atrial fibrillation, on warfarin, with known
      hyperthyroidism, was admitted to hospital following a fall with proptosis and
      severely restricted movements in her left eye. Medics initially thought the
      presentation was related to an intracranial pathology but through subsequent
      tests and examination, ophthalmologists diagnosed a severe case of thyroid eye
      disease with intense inflammation. The patient responded well to systemic steroid
      treatment. This case report highlights a severe rapidly progressing case of
      thyroid eye disease with diagnostic difficulties arising from multiple
      comorbidities in an elderly patient. 

PMID- 25754168
TI  - Infected florid osseous dysplasia: clinical and imaging follow-up.
AB  - Florid osseous dysplasia (FOD) is a rare fibro-osseous lesion of the jaw usually
      identified incidentally on radiograph. It rarely presents with clinical symptoms.
      A case of FOD presenting with features similar to osteomyelitis is discussed
      here. The diagnosis is based on radiographic findings; biopsy or surgical
      intervention should be avoided as it may predispose to infection. 

PMID- 25754169
TI  - Safety and cost analysis of an (18)FDG-PET-CT response based follow-up strategy
      for head and neck cancers treated with primary radiation or chemoradiation.
AB  - BACKGROUND: Prognostic information can rationalise clinical follow-up after
      radical cancer treatment. This retrospective cohort study of radical head and
      neck (chemo)radiotherapy patients examines the clinical safety and cost
      implications of stratifying follow-up intensity by post-treatment (18)FDG-PET-CT
      response. METHODS: In 2008 clinical review after radical head and neck
      radiotherapy was reduced from 3- to 6-monthly for patients with complete (18)FDG
      PET-CT response at 3months. 184 patients treated after this change ("PET
      Stratified", 2009-11) were compared to 178 patients treated before ("Standard",
      2005-7). Clinical safety was assessed by the time to detection of recurrence,
      overall survival and potential for radical treatment of recurrence. A hospital
      cost analysis was performed using individual patient data. RESULTS: 127 of 178
      Standard and 148 of 184 PET Stratified patients achieved complete response on
      post-treatment imaging. Baseline clinical characteristics were comparable. Median
      follow-up from response assessment was 4.8years in the Standard cohort and
      2.1years for PET Stratified. PET Stratified patients had a mean 4.4 outpatient
      visits in 2years, compared to 7.0 among Standard patients. Over 90% of patients
      remained free of recurrence at 2years in both cohorts. Time to detection of
      recurrence was similar between two cohorts (HR1.05, 95%CI 0.45-2.52), as was
      overall survival (HR0.91, 95%CI 0.36-2.29). The proportion of radically treatable
      recurrences was also similar (42% Standard vs. 47% PET Stratified). The hospital
      cost savings per patient from reduced review were AUD$2606 over 2years, AUD$5012
      over five. CONCLUSION: (18)FDG-PET-CT to stratify follow-up intensity after
      radical radiotherapy for head and neck cancer reduces costs with no apparent
      clinical detriment.

PMID- 25754170
TI  - ERCC1 plays an important role in predicting survival outcomes and treatment
      response for patients with HNSCC: a meta-analysis.
AB  - BACKGROUND: Excision repair crosscomplementing-1 (ERCC1) has been reported to
      play a prognostic role and may indicate the treatment response in patients with
      head and neck squamous carcinoma (HNSCC). Nevertheless, the strength of evidence
      of ERCC1 predicting these two clinical outcomes are still controversial. METHODS:
      Potentially eligible studies were retrieved using PubMed, Embase and Medline.
      Basic clinical characteristics of patients and statistical data with the survival
      data were collected. Then a meta-analysis model was established to investigate
      the correlation between over-expression of ERCC1 and survival outcome in HNSCC
      patients as well as to determine whether the treatment response is dependent on
      expression stature of ERCC1 or not. RESULTS: 17 eligible studies and 1263
      patients were yielded in our meta-analysis. The pooled HRs with 95% confidence
      intervals (CIs) for OS and PFS were 2.14 [1.51, 3.05] and 2.60 [1.98, 3.42],
      respectively. In terms of subgroup analysis, race was found to be a significant
      factor divided for these analyses, and the pooled HRs for the Asian subgroup are
      2.97 [2.05, 4.32] and 2.75 [1.82, 4.13] respectively. In non-Asian subgroup,
      Pooled HRs indicate the predict role for PFS 2.42 [1.60, 3.66], but no value for
      OS (P<0.05). With regard to treatment response, the pooled ORs were 3.04 [1.99,
      4.62]. Results from subgroup analysis that divided by race further showed that
      pooled ORs in Asian group were 3.95 [2.30, 6.78] and 1.93 [0.97, 3.84] in non
      Asian group. CONCLUSION: ERCC1 could be a fine prognostic factor of HNSCC and can
      also prompt the treatment response, which might be proven by further multicenter
      clinical trials.

PMID- 25754171
TI  - Contextual analysis of determinants of late diagnosis of hepatitis C virus
      infection in medicare patients.
AB  - Patient- and county-level characteristics associated with advanced liver disease
      (ALD) at hepatitis C virus (HCV) diagnosis were examined in three Medicare
      cohorts: (1) elderly born before 1945; (2) disabled born 1945-1965; and (3)
      disabled born after 1965. We used Medicare claims (2006-2009) linked to the Area
      Health Resource Files. ALD was measured over the period of 6 months before to 3
      months after diagnosis. Using weighted multivariate modified Poisson regression
      to address generalizability of findings to all Medicare patients, we modeled the
      association between contextual characteristics and presence of ALD at HCV
      diagnosis. We identified 1,746, 3,351, and 592 patients with ALD prevalence of
      28.0%, 23.0%, and 15.0% for birth cohorts 1, 2, and 3. Prevalence of drug abuse
      increased among younger birth cohorts (4.2%, 22.6%, and 35.6%, respectively).
      Human immunodeficiency virus coinfection (prevalence ratio [PR] = 0.63; 95%
      confidence interval [CI]: 0.50-0.80; P = 0.001), dual Medicare/Medicaid
      eligibility (PR = 0.89; 95% CI: 0.80-0.98; P = 0.017), residence in counties with
      higher median household income (PR = 0.82; 95% CI: 0.71-0.95; P = 0.008), higher
      density of primary care providers (PR = 0.84; 95% CI: 0.73-0.98; P = 0.022), and
      more rural health clinics (PR = 0.90; 0.81-1.01; P = 0.081) were associated with
      lower ALD risk. End-stage renal disease (PR = 1.41; 95% CI: 1.21-1.63; P =
      0.001), alcohol abuse (PR = 2.57; 95% CI: 2.33-2.84; P = 0.001), hepatitis B
      virus (PR = 1.32; 95% CI: 1.09-1.59; P = 0.004), and Midwest residence (PR =
      1.22; 95% CI: 1.05-1.41; P = 0.010) were associated with higher ALD risk. Living
      in rural counties with high screening capacity was protective in the elderly, but
      associated with higher ALD risk among the disabled born 1945-1965. CONCLUSIONS:
      ALD prevalence patterns were complex and were modified by race,
      elderly/disability status, and the extent of health care access and screening
      capacity in the county of residence. These study results help inform treatment
      strategies for HCV in the context of coordinated models of care.

PMID- 25754172
TI  - Kidney injury is independent of endothelial HIF-1alpha.
AB  - Hypoxia-inducible transcription factors (HIFs) control cellular adaptation to low
      oxygen. In the kidney, activation of HIF is beneficial during injury; however,
      the specific contribution of HIF-1alpha in renal endothelial cells (EC) remains
      elusive. Since EC display tissue-specific heterogeneity, we investigated how HIF
      1alpha affects key functions of glomerular EC in vitro and its contribution to
      renal development and pathophysiological adaptation to acute or chronic renal
      injury in vivo. Loss of HIF-1alpha in glomerular EC induces hypoxic cell death
      and reduces hypoxic adhesion of macrophages in vitro. In vivo, HIF-1alpha
      expression in EC in mouse kidneys is detectable but limited. Accordingly, EC
      specific ablation of HIF-1alpha does not lead to developmental or phenotypical
      abnormalities in the kidney. Renal function and expression of adhesion molecules
      during acute ischemic kidney injury is independent of HIF-1alpha in EC. Likewise,
      inflammation and development of fibrosis after unilateral ureteric obstruction is
      not influenced by endothelial HIF-1alpha. Taken together, although HIF-1alpha
      exerts effects on glomerular EC in vitro, endothelial HIF-1alpha does not
      influence renal development and pathophysiological adaptation to kidney injury in
      vivo. This implies a profound difference of the hypoxic response of the renal
      vascular bed compared to other organs, such as the heart. This has implications
      for the development of pharmacological strategies targeting the endothelial
      hypoxic response pathways. KEY MESSAGE: HIF-1alpha controls hypoxic survival and
      adhesion on endothelial cells (EC) in vitro. In vivo, HIF-1alpha expression in
      renal EC is low. Deletion of HIF-1alpha in EC does not affect kidney development
      and function in mice. Renal function after acute and chronic kidney injury is
      independent of HIF-1alpha in EC. Data suggest organ-specific regulation of HIF
      1alpha function in EC.

PMID- 25754173
TI  - Metal-deficient SOD1 in amyotrophic lateral sclerosis.
AB  - Mutations to the ubiquitous antioxidant enzyme Cu/Zn superoxide dismutase (SOD1)
      were the first established genetic cause of the fatal, adult-onset
      neurodegenerative disease amyotrophic lateral sclerosis (ALS). It is widely
      accepted that these mutations do not cause ALS via a loss of antioxidant
      function, but elucidating the alternate toxic gain of function has proven to be
      elusive. Under physiological conditions, SOD1 binds one copper ion and one zinc
      ion per monomer to form a highly stable and functional homodimer, but there is
      now ample evidence to indicate aberrant persistence of SOD1 in an intermediate
      metal-deficient state may contribute to the protein's involvement in ALS. This
      review briefly discusses some of the data to support a role for metal-deficient
      SOD1 in the development of ALS and some of the outcomes from drug development
      studies that have aimed to modify the symptoms of ALS by targeting the metal
      state of SOD1. The implications for the metal state of SOD1 in cases of sporadic
      ALS that do not involve mutant SOD1 are also discussed.

PMID- 25754174
TI  - Increased phosphate transport of Arabidopsis thaliana Pht1;1 by site-directed
      mutagenesis of tyrosine 312 may be attributed to the disruption of homomeric
      interactions.
AB  - Members of the Pht1 family of plant phosphate (Pi) transporters play vital roles
      in Pi acquisition from soil and in planta Pi translocation to maintain optimal
      growth and development. The study of the specificities and biochemical properties
      of Pht1 transporters will contribute to improving the current understanding of
      plant phosphorus homeostasis and use-efficiency. In this study, we show through
      split in vivo interaction methods and in vitro analysis of microsomal root
      tissues that Arabidopsis thaliana Pht1;1 and Pht1;4 form homomeric and
      heteromeric complexes. Transient and heterologous expression of the Pht1;1
      variants, Pht1;1(Y312D), Pht1;1(Y312A) and Pht1;1(Y312F), was used to analyse the
      role of a putative Pi binding residue (Tyr 312) in Pht1;1 transporter
      oligomerization and function. The homomeric interaction among Pht1;1 proteins was
      disrupted by mutation of Tyr 312 to Asp, but not to Ala or Phe. In addition, the
      Pht1;1(Y312D) variant conferred enhanced Pi transport when expressed in yeast
      cells. In contrast, mutation of Tyr 312 to Ala or Phe did not affect Pht1;1
      transport kinetics. Our study demonstrates that modifications to the Pht1;1
      higher-order structure affects Pi transport, suggesting that oligomerization may
      serve as a regulatory mechanism for modulating Pi uptake.

PMID- 25754175
TI  - Incidental necropsy finding of a quadricuspid aortic valve.
AB  - Quadricuspid aortic valve is a rare congenital cardiac malformation often
      associated with abnormal valve function. In this article, we present a case of
      quadricuspid aortic valve only diagnosed at the time of post-mortem examination. 

PMID- 25754177
TI  - Menstrual versus non-menstrual attacks of migraine without aura in women with and
      without menstrual migraine.
AB  - OBJECTIVE: The objective of this article is to compare clinical characteristics
      of menstrual and non-menstrual attacks of migraine without aura (MO),
      prospectively recorded in a headache diary, by women with and without a diagnosis
      of menstrual migraine without aura (MM) according to the International
      Classification of Headache Disorders (ICHD). MATERIAL AND METHODS: A total of 237
      women from the general population with self-reported migraine in >=50% of their
      menstrual periods were interviewed and classified by a physician according to the
      criteria of the ICHD II. Subsequently, all participants were instructed to
      complete a prospective headache diary for at least three menstrual cycles.
      Clinical characteristics of menstrual and non-menstrual attacks of MO were
      compared by a regression model for repeated measurements. RESULTS: In total, 123
      (52%) women completed the diary. In the 56 women who were prospectively diagnosed
      with MM by diary, the menstrual MO-attacks were longer (on average 10.65 hours,
      99% CI 3.17-18.12) and more frequently accompanied by severe nausea (OR 2.14, 99%
      CI 1.20-3.84) than non-menstrual MO-attacks. No significant differences between
      menstrual and non-menstrual MO-attacks were found among women with MO, but no MM.
      CONCLUSION: In women from the general population, menstrual MO-attacks differ
      from non-menstrual attacks only in women who fulfil the ICHD criteria for MM.

PMID- 25754176
TI  - Is migraine a risk factor for pediatric stroke?
AB  - IMPORTANCE: Our understanding of risk factors for childhood stroke is incomplete.
      In adults, migraine with aura is associated with a two-fold increase in ischemic
      stroke risk. OBJECTIVE: In this cohort study we examine the association between
      migraine and stroke among children in Kaiser Permanente Northern California
      (KPNC). DESIGN, SETTING, AND PARTICIPANTS: Children ages 2-17 years who were
      members of KPNC for >=6 months between 1997 and 2007 were included. Migraine
      cohort members had one or more of: an ICD-9 code for migraine, migraine listed as
      a significant health problem, or a prescription for a migraine-specific
      medication. The comparison group was children with no evidence of headache. MAIN
      OUTCOME MEASURES: Main outcome measures included stroke incidence rates and
      incidence rate ratios (IR). RESULTS: Among the 1,566,952 children within KPNC
      during the study period, 88,164 had migraine, and 1,323,142 had no evidence of
      headache. Eight migraineurs had a stroke (three (38%) hemorrhagic; five (63%)
      ischemic). Eighty strokes occurred in children without headache (53 (66%)
      hemorrhagic; 27 (34%) ischemic). The ischemic stroke incidence rate was
      0.9/100,000 person-years in migraineurs vs. 0.4/100,000 person-years in those
      without headache; IR 2.0 (95% CI 0.8-5.2). A post-hoc analysis of adolescents (12
      17 years) showed an increased risk of ischemic stroke among those with migraine;
      IR 3.4 (95% CI 1.2-9.5). The hemorrhagic stroke incidence rate was 0.5/100,000
      person-years in migraineurs and 0.9/100,000 person-years in those without
      headache; IR 0.6 (95% CI 0.2-2.0). CONCLUSIONS: There was no statistically
      significant increase in hemorrhagic or ischemic stroke risk in pediatric
      migraineurs in this cohort study. A post-hoc analysis found that ischemic stroke
      risk was significantly elevated in adolescents with migraine. Future studies
      should focus on identifying risk factors for ischemic stroke among adolescent
      migraineurs. Based on adult data, we recommend that migraine aura status should
      be studied as a possible risk factor for ischemic stroke among adolescent
      migraineurs.

PMID- 25754178
TI  - Infantile colic associated with childhood migraine: A prospective cohort study.
AB  - PURPOSE: To explore the association between infantile colic and adolescent
      migraine. METHOD: In a randomized general population sample, families expecting
      their first child were prospectively followed for infantile colic and adolescent
      migraine. RESULTS: Colic was diagnosed in 160 (13%) of 1267 infants until the age
      of 3 months. Migraine was ascertained in 129 (16%) of 787 adolescents at age 18
      years. History of infantile colic was identified in 96 (12%) of 787 adolescents
      and no such history in 658 (88%) of 787 adolescents. Migraine was present in 22
      (23%)/96 adolescents who had a history of infantile colic, but in only 74
      (11%)/658 ones who had no such history. Of the 22 adolescents, 14 (64%) had
      migraine without aura and eight (36%) had migraine with aura. Infants with colic
      had an almost three-fold risk (risk ratio 2.8, 95% confidence interval 1.2-6.5)
      for adolescent migraine without aura, but no increased risk for migraine with
      aura (0.8, 0.3-2.2). DISCUSSION AND CONCLUSIONS: Infantile colic seems to be
      associated with an increased risk for migraine without aura, but not for migraine
      with aura. Whether infantile colic per se is a type of infantile migraine or an
      antecedent of future migraine remains to be answered by further research.

PMID- 25754179
TI  - Our interface with the built environment: immunity and the indoor microbiota.
AB  - The rise of urbanization and an increasingly indoor lifestyle has affected human
      interactions with our microbiota in unprecedented ways. We discuss how this
      lifestyle may influence immune development and function, and argue that it is
      time that we examined ways to manipulate the indoor environment to increase our
      exposure to a wider phylogeny of microorganisms. An important step is to continue
      to engage citizen scientists in the efforts to characterize our interactions with
      the diverse microbial environments that we inhabit. 

PMID- 25754180
TI  - Reduction of bone dust with ultrasonic bone aspiration: implications for
      retrosigmoid vestibular schwannoma removal.
AB  - OBJECTIVE: Postoperative headache is not uncommon after retrosigmoid vestibular
      schwannoma removal. Bone dust dispersed into the subarachnoid space during
      drilling may be responsible. If dispersion could be reduced, headache incidence
      might be decreased. An ultrasonic bone aspirator (UBA) containing an integrated
      suction at the tip may more effectively suction bone dust created during bone
      removal. The objective is to determine whether a UBA results in less bone dust
      dispersion than a standard otologic drill. STUDY DESIGN: Cadaveric temporal bone
      quantitative model. SETTING: Laboratory. SUBJECTS AND METHODS: Temporal bone
      blocks were placed in a watertight enclosure. Under irrigation, bone was removed
      by use of either a drill or a UBA. The settings of the UBA were varied. The
      irrigant containing bone dust was microfiltered, and bone dust was weighed.
      Differences were compared across groups (n = 2-9 per group). Ablation times were
      also recorded (n = 3 per group). RESULTS: Only 3% (SD = 1.6%, n = 7) of the
      drilled bone mass was re-collected as bone dust with the UBA under optimized
      settings (power = 15%, suction = 100%, irrigation = 15 mL/min) compared with 81%
      (SD = 10%, n = 4) with the drill and external suction (P < .001). Increasing UBA
      power and reducing suction led to significantly more bone dust dispersal than
      with optimized settings. Varying irrigation did not have a significant effect.
      Bone ablation time was 1.4 times longer with the UBA at 50% power compared with
      the drill at maximum power. CONCLUSIONS: The UBA resulted in approximately 25
      times less bone dust dispersion than the otologic drill at optimized settings.

PMID- 25754181
TI  - Updating Clinical Practice Guidelines: How Do We Stay Current?
AB  - Clinical practice guidelines (CPGs) are created to address quality improvement
      opportunities for all clinicians, optimize patient care, promote effective
      diagnosis and therapy, and reduce harmful or unnecessary variations in patient
      care. Tremendous resources are invested in creating CPGs we can trust. Once a
      guideline is created, however, how is it maintained to reflect the most up-to
      date clinical evidence? This article reviews protocols for reviewing and
      maintaining CPGs with particular attention to the protocols established by the
      American Academy of Otolaryngology-Head and Neck Surgery. 

PMID- 25754182
TI  - Factors associated with hypertrophy of the lingual tonsils.
AB  - OBJECTIVE: To identify factors that may be associated with lingual tonsil
      hypertrophy (LTH). STUDY DESIGN: Case series with chart review. SETTING: Tertiary
      academic center. SUBJECTS AND METHODS: Retrospective chart review identified 380
      patients from August 2013 to April 2014 with graded lingual tonsils, documented
      during routine flexible laryngoscopy. Lingual tonsils were graded using a 0 to 4
      scale: 0 = complete absence of lymphoid tissue, 1 = lymphoid tissue scattered
      over tongue base, 2 = lymphoid tissue covers entirety of tongue base with limited
      thickness, 3 = lymphoid tissue 5 to 10 mm in thickness, 4 = lymphoid tissue >1 cm
      in thickness (rising above the tip of epiglottis). Reflux symptom index (RSI
      collected during patient intake), presence of obstructive sleep apnea hypopnea
      syndrome (OSAHS; confirmed by polysomnogram), smoking habits, and basic
      demographics were gathered. Chi-square and linear multivariate regression
      analyses were used to identify significant relationships with LTH levels.
      RESULTS: Overall, 59.8% were male with a mean age of 50.2 +/- 16.5 years and BMI
      of 30.1 +/- 18.0. Chi-square analysis revealed no significant relationship
      between OSAHS and LTH (P = .059). When RSI was stratified to >= 10 or < 10, a
      Cochran-Armitage test supported the trend hypothesis that as RSI increases,
      lingual tonsil grading increases. Significant univariate correlates included
      younger age (r = -0.307, P < .001) and smoking (r = 0.186, P = .002).
      Multivariate regression revealed the combination of younger age, increasing RSI,
      and smoking (r = -0.297, P < .001) to be a significant correlate. CONCLUSION: LTH
      does not seem to be associated with OSAHS or BMI in this group of patients. High
      RSI, younger age, and gender may be factors associated with increased lingual
      tonsil thickness.

PMID- 25754183
TI  - Ipsilateral reduced olfactory bulb volume in patients with unilateral nasal
      obstruction.
AB  - OBJECTIVES: To evaluate the effect of unilateral nasal obstruction (by nasal
      polyps of different histopathology) on olfactory bulb volume using MRI technique.
      STUDY DESIGN: Cross-sectional study. SETTING: Tertiary university hospitals,
      Departments of Otolaryngology and Radiology. SUBJECTS AND METHODS: Eleven
      patients with a few months of complete unilateral nasal obstruction of different
      pathological etiologies were selected. MRI assessment of olfactory bulb volume
      was performed using planimetric manual contouring. The contralateral olfactory
      bulb was used as a comparative control for the same patient. Eleven healthy
      controls constituted the control group. RESULTS: Mean olfactory bulb volume +/-
      SD of obstructed side = 14.3 +/- 3.7 mm(3), mean olfactory bulb volume +/- SD of
      nonobstructed side = 43.49 +/- 10.7 mm(3). The difference between the 2 sides was
      significant (P = .003). The difference in olfactory bulb volume between normal
      subjects and nonobstructed nasal side was statistically nonsignificant (t =
      .9118, P = .3727), while the difference between normal subjects' olfactory bulb
      volume and obstructed nasal side olfactory bulb volume in our patients was
      extremely statistically significant (t = 9.7320, P < .0001). A strong negative
      correlation was found between duration of obstruction and olfactory bulb volume
      (R = -0.9761). CONCLUSION: This study shows that unilateral nasal obstruction may
      be associated with a lateralized ipsilateral difference of olfactory bulb volume.

PMID- 25754185
TI  - A novel microwave sensor for real-time online monitoring of roll compacts of
      pharmaceutical powders online--a comparative case study with NIR.
AB  - Control of particulate processes is hard to achieve because of the ease with
      which powders tend to segregate. Thus, proper sensing methods must be employed to
      ensure content uniformity during operation. The role of sensing schemes becomes
      even more critical while operating the process continuously as measurements are
      essential for implementation of feedback control (Austin et al. 2013. J Pharm Sci
      102(6):1895-1904; Austin et al. 2014. Anal Chim Acta 819:82-93). A microwave
      sensor was developed and shown to be effective in online measurement of active
      pharmaceutical ingredient (API) concentration in a powder blend. During powder
      transport and hopper storage before processing, powder blends may segregate and
      cause quality deviations in the subsequent tableting operation. Therefore, it is
      critical to know the API concentration in the ribbons as the content uniformity
      is fixed once the ribbon is processed. In this study, a novel microwave sensor
      was developed that could provide measurement of a roller compacted ribbon's API
      concentration online, along with its density and moisture content. The results
      indicate that this microwave sensor is capable of increased accuracy compared
      with a commercially available near-IR probe for the determination of content
      uniformity and density in roller compacted ribbons online.

PMID- 25754184
TI  - Rapamycin inhibits human laryngotracheal stenosis-derived fibroblast
      proliferation, metabolism, and function in vitro.
AB  - OBJECTIVE: To determine if rapamycin inhibits the growth, function, and
      metabolism of human laryngotracheal stenosis (LTS)-derived fibroblasts. STUDY
      DESIGN: Controlled in vitro study. SETTING: Tertiary care hospital in a research
      university. SUBJECTS AND METHODS: Fibroblasts isolated from biopsies of 5
      patients with laryngotracheal stenosis were cultured. Cell proliferation,
      histology, gene expression, and cellular metabolism of LTS-derived fibroblasts
      were assessed in 4 conditions: (1) fibroblast growth medium, (2) fibroblast
      growth medium with dimethylsulfoxide (DMSO), (3) fibroblast growth medium with
      10(-10) M (low-dose) rapamycin dissolved in DMSO, and (4) fibroblast growth
      medium with 10(-9) M (high-dose) rapamycin dissolved in DMSO. RESULTS: The LTS
      fibroblast count and DNA concentration were reduced after treatment with high
      dose rapamycin compared to DMSO (P = .0007) and normal (P = .0007) controls.
      Collagen I expression decreased after treatment with high-dose rapamycin versus
      control (P = .0051) and DMSO (P = .0093) controls. Maximal respiration decreased
      to 68.6 pMoles of oxygen/min/10 mg/protein from 96.9 for DMSO (P = .0002) and
      97.0 for normal (P = .0022) controls. Adenosine triphosphate (ATP) production
      decreased to 66.8 pMoles from 88.1 for DMSO (P = .0006) and 83.3 for normal (P =
      .0003) controls. Basal respiration decreased to 78.6 pMoles from 108 for DMSO (P
      = .0002) and 101 for normal (P = .0014) controls. CONCLUSIONS: Rapamycin
      demonstrated an anti-fibroblast effect by significantly reducing the
      proliferation, metabolism, and collagen deposition of human LTS fibroblast in
      vitro. Rapamycin significantly decreased oxidative phosphorylation of LTS
      fibroblasts, suggesting at a potential mechanism for the reduced proliferation
      and differentiation. Furthermore, rapamycin's anti-fibroblast effects indicate a
      promising adjuvant therapy for the treatment of laryngotracheal stenosis.

PMID- 25754186
TI  - Improvements in Unmarried African American Parents' Rapport, Communication, and
      Problem-Solving Following a Prenatal Coparenting Intervention.
AB  - This report examines effects of a coparenting intervention designed for and
      delivered to expectant unmarried African American mothers and fathers on observed
      interaction dynamics known to predict relationship adjustment. Twenty families
      took part in the six-session "Figuring It Out for the Child" (FIOC) dyadic
      intervention offered in a faith-based human services agency during the third
      trimester of the mother's pregnancy, and completed a postpartum booster session 1
      month after the baby's arrival. Parent referrals for the FIOC program were
      received from a county Health Department and from OBGYNs and Pregnancy Centers in
      the targeted community. All intervention sessions were delivered by a trained
      male-female paraprofessional team whose fidelity to the FIOC manualized
      curriculum was independently evaluated by a team of trained analysts. At both the
      point of intake ("PRE") and again at an exit evaluation completed 3 months
      postpartum ("POST"), the mothers and fathers were videotaped as they completed
      two standardized "revealed differences" conflict discussions. Blinded videotapes
      of these sessions were evaluated using the System for Coding Interactions in
      Dyads. Analyses documented statistically significant improvements on 8 of 12
      variables examined, with effect sizes ranging from moderate to large. Overall, 14
      families demonstrated beneficial outcomes, 3 did not improve, and 3 showed some
      signs of decline from the point of intake. For most interaction processes, PRE to
      POST improvements were unrelated to degree of adherence the paraprofessional
      interventionists showed to the curriculum. However, better interventionist
      competence was related to decreases in partners' Coerciveness and Negativity and
      Conflict, and to smaller increases in partner Withdrawal. Implications of the
      work for development and delivery of community-based coparenting interventions
      for unmarried parents are discussed.

PMID- 25754187
TI  - Testing reliability and validity of oral impacts on daily performances for
      Chinese-speaking elderly Singaporeans.
AB  - OBJECTIVE: To cross-culturally adapt the oral impacts on daily performance (OIDP)
      and assess its reliability and validity on Chinese-speaking community dwelling
      elderly Singaporeans. BACKGROUND: There are no previous reports of valid oral
      health-related quality of life instruments for elderly Singaporeans or perceived
      conditions associated with impacts reported in OIDP among the Singaporean elders.
      METHODS: The OIDP was translated from English to Chinese and then back
      translated. The OIDP questionnaire along with questions related to overall
      quality of life and self-rated dental health was administered to 202 Chinese
      speaking elderly Singaporeans by trained interviewers, and it was repeated after
      1 month. Test-retest reliability was assessed using intraclass correlation
      coefficient; internal consistency was established using Cronbach's alpha, and
      construct validity using correlation coefficients with self-reported oral health
      related and global quality of life measures. In addition, Kruskal-Wallis tests
      assessed differences in the OIDP score between different subjective health and
      global quality of life groups. RESULTS: The median age of participants was 75
      years. About 19% reported oral impacts and difficulty eating was the most
      prevalent oral impact. Internal consistency was good with a Cronbach's alpha of
      0.75, and the intraclass correlation coefficient was 0.75 (0.67-0.81). OIDP was
      significantly correlated with all measures of self-reported oral health and
      global ratings of quality of life, with correlation coefficients ranging between
      0.15 and 0.52. Groups with worse perceptions about their health and quality of
      life had significantly higher OIDP scores. CONCLUSION: The OIDP showed successful
      reliability and validity for its use among Chinese-speaking older Singaporeans.

PMID- 25754189
TI  - EPOS 34th Annual Meeting.

PMID- 25754188
TI  - Alkalinized lidocaine versus lidocaine gel as local anesthesia prior to intra
      vesical botulinum toxin (BoNTA) injections: A prospective, single center,
      randomized, double-blind, parallel group trial of efficacy and morbidity.
AB  - AIMS: To assess the efficacy and morbidity of alkalinized lidocaine solution
      compared to lidocaine gel for intra-vesical anesthesia during botulinum toxin
      (BoNTA) injections in a statistically powered, prospective, parallel group,
      double-blind randomized controlled trial. METHODS: Fifty-four patients of either
      sex were randomized to receive either alkalinized lidocaine (AL) solution (10 ml
      8.4% sodium bicarbonate + 20 ml 2% lidocaine solution + 22 ml sterile Aquagel(r))
      or lidocaine gel (LG) (22 ml standard 2% lidocaine gel Instillagel(r) + 30 ml
      0.9% normal saline solution). Primary outcome was average pain (assessed by 100
      mm visual analog score) felt during intra-vesical BoNTA injections performed at
      least 20 min after instillation. Secondary outcome was the rate of adverse
      events. RESULTS: Of 60 randomized patients 54 received the allocated intervention
      and were analyzed. Mean pain score in the AL group was 17.11 mm (95%CI 8.65-25.57
      mm) and in the LG group was 19.53 mm (95%CI 13.03-26.03mm) with no significant
      difference between the groups. Cost of interventional medication in the AL group
      was almost double that of the LG group. No adverse events were attributable to
      local anesthetic instillation in either group. CONCLUSIONS: Alkalinized lidocaine
      solution is not superior to lidocaine gel for anesthesia during intra-vesical
      BoNTA injections, and the higher cost precludes its use over lidocaine gel at our
      centre. We have used the results of this study to adapt our local protocol for
      BoNTA injections and continue to use lidocaine gel as the local anesthetic of
      choice. Neurourol. Urodynam. 35:522-527, 2016. (c) 2015 Wiley Periodicals, Inc.

PMID- 25754191
TI  - Objective markers for sleep propensity: comparison between the Multiple Sleep
      Latency Test and the Vigilance Algorithm Leipzig.
AB  - The regulation of wakefulness is important for high-order organisms. Its
      dysregulation is involved in the pathomechanism of several psychiatric disorders.
      Thus, a tool for its objective but little time-consuming assessment would be of
      importance. The Vigilance Algorithm Leipzig allows the objective measurement of
      sleep propensity, based on a single resting state electroencephalogram. To
      compare the Vigilance Algorithm Leipzig with the standard for objective
      assessment of excessive daytime sleepiness, a four-trial Multiple Sleep Latency
      Test in 25 healthy subjects was conducted. Between the first two trials, a 15
      min, 25-channel resting electroencephalogram was recorded, and Vigilance
      Algorithm Leipzig was used to classify the sleep propensity (i.e., type of
      vigilance regulation) of each subject. The results of both methods showed
      significant correlations with the Epworth Sleepiness Scale (rho = -0.70; rho =
      0.45, respectively) and correlated with each other (rho = -0.54). Subjects with a
      stable electroencephalogram-vigilance regulation yielded significant increased
      sleep latencies compared with an unstable regulation (multiple sleep latency
      898.5 s versus 549.9 s; P = 0.03). Further, Vigilance Algorithm Leipzig
      classifications allowed the identification of subjects with average sleep
      latencies <6 min with a sensitivity of 100% and a specificity of 77%. Thus,
      Vigilance Algorithm Leipzig provides similar information on wakefulness
      regulation in comparison to the much more cost- and time-consuming Multiple Sleep
      Latency Test. Due to its high sensitivity and specificity for large sleep
      propensity, Vigilance Algorithm Leipzig could be an effective and reliable
      alternative to the Multiple Sleep Latency Test, for example for screening
      purposes in large cohorts, where objective information about wakefulness
      regulation is needed.

PMID- 25754192
TI  - Transcriptome changes induced by chronic psychosocial/environmental or
      neuroendocrine stressors reveal a selective cellular vulnerability of cortical
      somatostatin (SST) neurons, compared with pyramidal (PYR) neurons.

PMID- 25754190
TI  - Relationship of adiponectin and leptin with autoimmunity in children with new
      onset type 1 diabetes: a pilot study.
AB  - AIM: To explore racial differences in adiponectin, and leptin and their
      relationship with islet autoimmunity in children with new-onset type 1 diabetes
      (T1D). METHODS: Medical records were reviewed from a cohort of new-onset
      clinically diagnosed T1D subjects matched by race, age, gender, and year of
      diagnosis. Sera were available for 156 subjects (77 African American (AA), 79
      Caucasian (C), 48% male, age of 11.1 +/- 3.8 yr) and assayed for adiponectin and
      leptin prior to (D0), 3, 5 d, and 2-4 months (M3) after insulin therapy and islet
      autoantibodies to GAD, IA2, insulin, and ICA were measured at onset. RESULTS:
      Adiponectin levels increased significantly following insulin therapy by day 5
      (D5) (D0: 13.7 +/- 7.2 vs. D5: 21.3 +/- 9.9 ug/mL, p < 0.0001), but no further
      significant increase from D5 to M3. At DO, AA had lower adiponectin levels (10.5
      vs. 15.7 ug/mL, p = 0.01), were more often overweight than C (55 vs. 18%, BMI >=
      85th0/00) and fewer had positive autoantibodies (72 vs. 87%, p = 0.05). Racial
      differences in adipocytokines disappeared after adjustment for BMI. At M3,
      subjects with more number of positive autoantibodies had higher adiponectin
      levels (p = 0.043) and adiponectin/leptin ratio (ALR) (p = 0.01), and lower
      leptin levels (p = 0.016). CONCLUSION: Adiponectin levels increased acutely with
      insulin therapy. Significantly lower adiponectin levels in AA were related to
      greater adiposity and not race. These pilot data showing those with the fewest
      autoantibodies had the lowest adiponectin levels, supporting the concept that
      insulin-resistant subjects may present with clinical T1D at earlier stages of
      beta-cell damage.

PMID- 25754193
TI  - Body dissatisfaction and disordered eating among Portuguese and Spanish
      adolescents: The role of individual characteristics and internalisation of
      sociocultural ideals.
AB  - The aim of this study was to explore the differences in patterns of risk factors
      for body dissatisfaction and disordered eating attitudes in both female and male
      adolescents from Portugal and Spain. The sample included 455 adolescents aged 12
      16 years (M = 13.28, SD = 0.65) from two urban areas of each country. Body mass
      index, self-reported self-esteem, perfectionism, internalisation of sociocultural
      ideals, body dissatisfaction and disordered eating attitudes were assessed. Path
      analyses provided partial support for a cross-cultural model of body
      dissatisfaction and disordered eating in Western countries due to the presence of
      certain differences in the patterns of relationships across sex and country. The
      findings suggest the importance not only of identifying cultural specificities,
      even in "neighbouring" countries, but also of developing a global and
      comprehensive preventive approach that focuses on the influence of the ideal of
      beauty transmitted by Western societies. 

PMID- 25754195
TI  - Mild maturational delay of the brainstem at term in late preterm small-for
      gestation age babies.
AB  - AIMS: To detect any functional abnormality in the brainstem auditory pathway in
      late preterm babies born of small-for-gestational age (SGA) using maximum length
      sequence brainstem evoked response. STUDY DESIGN: The response was recorded and
      analyzed at term in 38 SGA (birthweight <3rd centile) babies born at 33-36 week
      gestation. The results were compared with 40 age-matched babies born of
      appropriate-for-gestational age (AGA) (birthweight >10th centile). None of the
      subjects had major perinatal problems. RESULTS: All wave latencies and interpeak
      intervals in the SGA group were slightly longer than those in the AGA group at
      most click rates. Wave III latency was significantly longer than that in the AGA
      group at 227/s (P < 0.05), and wave V latency was at 227 and 910/s (P < 0.05 and
      0.05). Of the interpeak intervals, only the I-V interval in the SGA group was
      significantly longer than that in the AGA group at the highest rate 910/s (P <
      0.05). The amplitudes of waves I, III and V in the SGA group all tended to be
      smaller than those in the AGA group at all click rates 91-910/s. The wave V
      amplitude was significantly smaller at most click rates (227-910/s, all P <
      0.05). The slopes of all wave latency-, interval-, and amplitude-rate functions
      were similar in SGA and AGA groups. CONCLUSIONS: There were marginal
      abnormalities in MLS BAER of low-risk late preterm SGA babies, suggesting a mild
      degree of maturational delay in the brainstem. Intrauterine growth retardation
      occurring in late preterm babies has a minor effect on neural maturation of the
      immature brainstem.

PMID- 25754194
TI  - The depression distress amplification model in adolescents: A longitudinal
      examination of anxiety sensitivity cognitive concerns, depression and suicidal
      ideation.
AB  - Adolescents with comorbid anxiety and depression are at significantly increased
      risk of suicide. The recently proposed depression distress amplification model
      appears to have promise for explaining the relations between anxiety, depression,
      and suicidality, but it has not been tested in adolescents. Participants were 524
      adolescents followed over two years. Baseline data for the current report were
      collected by trained interviewers while the adolescents were in eighth grade.
      Data were obtained in the same manner when the adolescents were in tenth grade.
      Baseline anxiety sensitivity cognitive concerns significantly predicted suicidal
      ideation two years later, above and beyond baseline suicidal ideation and
      depression. Further, consistent with the depression distress amplification model,
      anxiety sensitivity cognitive concerns interacted with depressive symptoms to
      predict suicidal ideation. This report extends the empirical and theoretical
      support for a relationship between anxiety sensitivity cognitive concerns and
      suicidality. 

PMID- 25754196
TI  - Hfq plays important roles in virulence and stress adaptation in Cronobacter
      sakazakii ATCC 29544.
AB  - Cronobacter spp. are opportunistic pathogens that cause neonatal meningitis and
      sepsis with high mortality in neonates. Despite the peril associated with
      Cronobacter infection, the mechanisms of pathogenesis are still being unraveled.
      Hfq, which is known as an RNA chaperone, participates in the interaction with
      bacterial small RNAs (sRNAs) to regulate posttranscriptionally the expression of
      various genes. Recent studies have demonstrated that Hfq contributes to the
      pathogenesis of numerous species of bacteria, and its roles are varied between
      bacterial species. Here, we tried to elucidate the role of Hfq in C. sakazakii
      virulence. In the absence of hfq, C. sakazakii was highly attenuated in
      dissemination in vivo, showed defects in invasion (3-fold) into animal cells and
      survival (10(3)-fold) within host cells, and exhibited low resistance to hydrogen
      peroxide (10(2)-fold). Remarkably, the loss of hfq led to hypermotility on soft
      agar, which is contrary to what has been observed in other pathogenic bacteria.
      The hyperflagellated bacteria were likely to be attributable to the increased
      transcription of genes associated with flagellar biosynthesis in a strain lacking
      hfq. Together, these data strongly suggest that hfq plays important roles in the
      virulence of C. sakazakii by participating in the regulation of multiple genes. 

PMID- 25754197
TI  - Trypanosoma cruzi trans-sialidase prevents elicitation of Th1 cell response via
      interleukin 10 and downregulates Th1 effector cells.
AB  - The trans-sialidases (TSs) from Trypanosoma cruzi, the agent of Chagas disease,
      are virulence factors shed to the bloodstream that induce strong alterations in
      the immune system. Here, we report that both enzymatically active TS (aTS) and
      its lectinlike isoform (iTS) disturb CD4 T cell physiology, inducing
      downregulation of Th1 cell functionality and in vivo cell expansion. By using
      ovalbumin-specific DO11.10 cells as tracers of clones developing the Th1
      phenotype, we found that the infection induced significant amounts of gamma
      interferon (IFN-gamma) but low levels of interleukin 2 (IL-2) and increased IL-4
      production in vivo, in agreement with a mixed T helper response. The production
      of cytokines associated with the Th2 phenotype was prevented by passive transfer
      of anti-TS neutralizing antibodies. TSs also reduced the T cell receptor
      signaling as assayed by Zap-70 phosphorylation. TSs also reduced IL-2 and IFN
      gamma secretion, with a concomitant increase in IL-4 production and then an
      unbalancing of the CD4 T cell response toward the Th2 phenotype. This effect was
      prevented by using anti-IL-10 neutralizing antibodies or IL-10(-/-) antigen
      presenting cells, supporting the subversion of this regulatory pathway. In
      support, TSs stimulated IL-10 secretion by antigen-presenting cells during their
      interaction with CD4 T cells. When polarized cells were stimulated in the
      presence of TSs, the secretion of IL-2 and IFN-gamma was strongly downregulated
      in Th1 cells, while IL-2 production was upregulated in Th2 cells. Although the
      Th1 response is associated with host survival, it may simultaneously induce
      extensive damage to infected tissues. Thus, by delaying the elicitation of the
      Th1 response and limiting its effector properties, TSs restrain the cell
      response, supporting T. cruzi colonization and persistence while favoring host
      survival. 

PMID- 25754198
TI  - High-throughput, signature-tagged mutagenic approach to identify novel virulence
      factors of Yersinia pestis CO92 in a mouse model of infection.
AB  - The identification of new virulence factors in Yersinia pestis and understanding
      their molecular mechanisms during an infection process are necessary in designing
      a better vaccine or to formulate an appropriate therapeutic intervention. By
      using a high-throughput, signature-tagged mutagenic approach, we created 5,088
      mutants of Y. pestis strain CO92 and screened them in a mouse model of pneumonic
      plague at a dose equivalent to 5 50% lethal doses (LD50) of wild-type (WT) CO92.
      From this screen, we obtained 118 clones showing impairment in disseminating to
      the spleen, based on hybridization of input versus output DNA from mutant pools
      with 53 unique signature tags. In the subsequent screen, 20/118 mutants exhibited
      attenuation at 8 LD50 when tested in a mouse model of bubonic plague, with
      infection by 10/20 of the aforementioned mutants resulting in 40% or higher
      survival rates at an infectious dose of 40 LD50. Upon sequencing, six of the
      attenuated mutants were found to carry interruptions in genes encoding
      hypothetical proteins or proteins with putative functions. Mutants with in-frame
      deletion mutations of two of the genes identified from the screen, namely, rbsA,
      which codes for a putative sugar transport system ATP-binding protein, and vasK,
      a component of the type VI secretion system, were also found to exhibit some
      attenuation at 11 or 12 LD50 in a mouse model of pneumonic plague. Likewise,
      among the remaining 18 signature-tagged mutants, 9 were also attenuated (40 to
      100%) at 12 LD50 in a pneumonic plague mouse model. Previously, we found that
      deleting genes encoding Braun lipoprotein (Lpp) and acyltransferase (MsbB), the
      latter of which modifies lipopolysaccharide function, reduced the virulence of Y.
      pestis CO92 in mouse models of bubonic and pneumonic plague. Deletion of rbsA and
      vasK genes from either the Deltalpp single or the Deltalpp DeltamsbB double
      mutant augmented the attenuation to provide 90 to 100% survivability to mice in a
      pneumonic plague model at 20 to 50 LD50. The mice infected with the Deltalpp
      DeltamsbB DeltarbsA triple mutant at 50 LD50 were 90% protected upon subsequent
      challenge with 12 LD50 of WT CO92, suggesting that this mutant or others carrying
      combinational deletions of genes identified through our screen could potentially
      be further tested and developed into a live attenuated plague vaccine(s). 

PMID- 25754199
TI  - Superantigenic Yersinia pseudotuberculosis induces the expression of granzymes
      and perforin by CD4+ T cells.
AB  - Bacterial superantigens (SAgs) are immunostimulatory toxins that induce acute
      diseases mainly through the massive release of inflammatory cytokines. Yersinia
      pseudotuberculosis is the only Gram-negative bacterium known to produce a SAg (Y.
      pseudotuberculosis-derived mitogen [YPM]). This SAg binds major
      histocompatibility complex class II molecules on antigen-presenting cells and T
      cell receptors (TcR) bearing the variable region Vbeta3, Vbeta9, Vbeta13.1, or
      Vbeta13.2 (in humans) and Vbeta7 or Vbeta8 (in mice). We have previously shown
      that YPM exacerbates the virulence of Y. pseudotuberculosis in mice. With a view
      to understanding the mechanism of YPM's toxicity, we compared the immune response
      in BALB/c mice infected with a YPM-producing Y. pseudotuberculosis or the
      corresponding isogenic, SAg-deficient mutant. Five days after infection, we
      observed strong CD4(+) Vbeta7(+) T cell expansion and marked interleukin-4 (IL-4)
      production in mice inoculated with SAg-producing Y. pseudotuberculosis. These
      phenomena were correlated with the activation of ypm gene transcription in liver
      and spleen. A transcriptomic analysis revealed that the presence of YPM also
      increased expression of granzyme and perforin genes in the host's liver and
      spleen. This expression was attributed to a CD4(+) T cell subset, rather than to
      natural killer T (NKT) cells that display a TcR with a Vbeta region that is
      potentially recognized by YPM. Increased production of cytotoxic molecules was
      correlated with hepatotoxicity, as demonstrated by an increase in plasma alanine
      aminotransferase activity. Our results demonstrate that YPM activates a
      potentially hepatotoxic CD4(+) T cell population. 

PMID- 25754200
TI  - Interleukin-6-driven inflammatory response induces retinal pathology in a model
      of ocular toxoplasmosis reactivation.
AB  - Ocular inflammation is one of the consequences of infection with the protozoan
      parasite Toxoplasma gondii. Even if lesions are self-healing in immunocompetent
      persons, they pose a lifetime risk of reactivation and are a serious threat to
      vision. As there are virtually no immunological data on reactivating ocular
      toxoplasmosis, we established a model of direct intravitreal injection of
      parasites in previously infected mice with a homologous type II strain. Two
      different mouse strains with variable ability to control retinal infection were
      studied in order to describe protective and deleterious reaction patterns. In
      Swiss-Webster mice, which are already relatively resistant to primary infection,
      no peak of parasite load was observed upon reinfection. In contrast, the
      susceptible inbred strain C57BL/6 showed high parasite loads after 7 days, as
      well as marked deterioration of retinal architecture. Both parameters were back
      to normal on day 21. C57BL/6 mice also reacted with a strong local production of
      inflammatory and Th1-type cytokines, like interleukin-6 (IL-6), IL-17A, and gamma
      interferon (IFN-gamma), while Swiss-Webster mice showed only moderate expression
      of the Th2 cytokine IL-31. Interestingly, rapid intraocular production of anti
      Toxoplasma antibodies was observed in Swiss-Webster but not in C57BL/6 mice. We
      then localized the cellular source of different immune mediators within the
      retina by immunofluorescence. Finally, neutralization experiments of IFN-gamma or
      IL-6 demonstrated the respective protective and deleterious roles of these
      cytokines for parasite control and retinal integrity during reinfection. In
      conclusion, we developed and immunologically characterized a promising mouse
      model of reactivating ocular toxoplasmosis. 

PMID- 25754201
TI  - Ethanol impairs mucosal immunity against Streptococcus pneumoniae infection by
      disrupting interleukin 17 gene expression.
AB  - Acute ethanol intoxication suppresses the host immune responses against
      Streptococcus pneumoniae. As interleukin 17 (IL-17) is a critical cytokine in
      host defense against extracellular pathogens, including S. pneumoniae, we
      hypothesized that ethanol impairs mucosal immunity against this pathogen by
      disrupting IL-17 production or IL-17 receptor (IL-17R) signaling. A chronic
      ethanol feeding model in simian immunodeficiency virus (SIV)-infected rhesus
      macaques and acute ethanol intoxication in a murine model were used.
      Transcriptome analysis of bronchial brushes in the nonhuman primate model showed
      downregulation of the expression of IL-17-regulated chemokines in ethanol-fed
      animals, a finding also replicated in the murine model. Surprisingly, recombinant
      CXCL1 and CXCL5 but not IL-17 or IL-23 plus IL-1beta rescued bacterial burden in
      the ethanol group to control levels. Taken together, the results of this study
      suggest that ethanol impairs IL-17-mediated chemokine production in the lung.
      Thus, exogenous luminal restoration of IL-17-related chemokines, CXCL1 and CXCL5,
      improves host defenses against S. pneumoniae. 

PMID- 25754203
TI  - The PI3K pathway balances self-renewal and differentiation of nephron progenitor
      cells through beta-catenin signaling.
AB  - Nephron progenitor cells differentiate to form nephrons during embryonic kidney
      development. In contrast, self-renewal maintains progenitor numbers and premature
      depletion leads to impaired kidney function. Here we analyze the PI3K pathway as
      a point of convergence for the multiple pathways that are known to control self
      renewal in the kidney. We demonstrate that a reduction in PI3K signaling triggers
      premature differentiation of the progenitors and activates a differentiation
      program that precedes the mesenchymal-to-epithelial transition through ectopic
      activation of the beta-catenin pathway. Therefore, the combined output of PI3K
      and other pathways fine-tunes the balance between self-renewal and
      differentiation in nephron progenitors. 

PMID- 25754202
TI  - Protein energy malnutrition during vaccination has limited influence on vaccine
      efficacy but abolishes immunity if administered during Mycobacterium tuberculosis
      infection.
AB  - Protein energy malnutrition (PEM) increases susceptibility to infectious
      diseases, including tuberculosis (TB), but it is not clear how PEM influences
      vaccine-promoted immunity to TB. We demonstrate that PEM during low-level steady
      state TB infection in a mouse model results in rapid relapse of Mycobacterium
      tuberculosis, as well as increased pathology, in both Mycobacterium bovis BCG
      vaccinated and unvaccinated animals. PEM did not change the overall numbers of
      CD4 T cells in BCG-vaccinated animals but resulted in an almost complete loss of
      antigen-specific cytokine production. Furthermore, there was a change in cytokine
      expression characterized by a gradual loss of multifunctional antigen-specific
      CD4 T cells and an increased proportion of effector cells expressing gamma
      interferon and tumor necrosis factor alpha (IFN-gamma(+) TNF-alpha(+) and IFN
      gamma(+) cells). PEM during M. tuberculosis infection completely blocked the
      protection afforded by the H56-CAF01 subunit vaccine, and this was associated
      with a very substantial loss of the interleukin-2-positive memory CD4 T cells
      promoted by this vaccine. Similarly, PEM during the vaccination phase markedly
      reduced the H56-CAF01 vaccine response, influencing all cytokine-producing CD4 T
      cell subsets, with the exception of CD4 T cells positive for TNF-alpha only.
      Importantly, this impairment was reversible and resupplementation of protein
      during infection rescued both the vaccine-promoted T cell response and the
      protective effect of the vaccine against M. tuberculosis infection.

PMID- 25754204
TI  - The polycomb group protein L3MBTL1 represses a SMAD5-mediated hematopoietic
      transcriptional program in human pluripotent stem cells.
AB  - Epigenetic regulation of key transcriptional programs is a critical mechanism
      that controls hematopoietic development, and, thus, aberrant expression patterns
      or mutations in epigenetic regulators occur frequently in hematologic
      malignancies. We demonstrate that the Polycomb protein L3MBTL1, which is
      monoallelically deleted in 20q- myeloid malignancies, represses the ability of
      stem cells to drive hematopoietic-specific transcriptional programs by regulating
      the expression of SMAD5 and impairing its recruitment to target regulatory
      regions. Indeed, knockdown of L3MBTL1 promotes the development of hematopoiesis
      and impairs neural cell fate in human pluripotent stem cells. We also found a
      role for L3MBTL1 in regulating SMAD5 target gene expression in mature
      hematopoietic cell populations, thereby affecting erythroid differentiation.
      Taken together, we have identified epigenetic priming of hematopoietic-specific
      transcriptional networks, which may assist in the development of therapeutic
      approaches for patients with anemia. 

PMID- 25754205
TI  - The p53 isoform Delta133p53beta promotes cancer stem cell potential.
AB  - Cancer stem cells (CSC) are responsible for cancer chemoresistance and metastasis
      formation. Here we report that Delta133p53beta, a TP53 splice variant, enhanced
      cancer cell stemness in MCF-7 breast cancer cells, while its depletion reduced
      it. Delta133p53beta stimulated the expression of the key pluripotency factors
      SOX2, OCT3/4, and NANOG. Similarly, in highly metastatic breast cancer cells,
      aggressiveness was coupled with enhanced CSC potential and Delta133p53beta
      expression. Like in MCF-7 cells, SOX2, OCT3/4, and NANOG expression were
      positively regulated by Delta133p53beta in these cells. Finally, treatment of MCF
      7 cells with etoposide, a cytotoxic anti-cancer drug, increased CSC formation and
      SOX2, OCT3/4, and NANOG expression via Delta133p53, thus potentially increasing
      the risk of cancer recurrence. Our findings show that Delta133p53beta supports
      CSC potential. Moreover, they indicate that the TP53 gene, which is considered a
      major tumor suppressor gene, also acts as an oncogene via the Delta133p53beta
      isoform. 

PMID- 25754206
TI  - Direct reprogramming of human bone marrow stromal cells into functional renal
      cells using cell-free extracts.
AB  - The application of cell-based therapies in regenerative medicine is gaining
      recognition. Here, we show that human bone marrow stromal cells (BMSCs), also
      known as bone-marrow-derived mesenchymal cells, can be reprogrammed into renal
      proximal tubular-like epithelial cells using cell-free extracts. Streptolysin-O
      permeabilized BMSCs exposed to HK2-cell extracts underwent morphological changes
      formation of "domes" and tubule-like structures-and acquired epithelial
      functional properties such as transepithelial-resistance, albumin-binding, and
      uptake and specific markers E-cadherin and aquaporin-1. Transmission electron
      microscopy revealed the presence of brush border microvilli and tight
      intercellular contacts. RNA sequencing showed tubular epithelial transcript
      abundance and revealed the upregulation of components of the EGFR pathway.
      Reprogrammed BMSCs integrated into self-forming kidney tissue and formed tubular
      structures. Reprogrammed BMSCs infused in immunodeficient mice with cisplatin
      induced acute kidney injury engrafted into proximal tubuli, reduced renal injury
      and improved function. Thus, reprogrammed BMSCs are a promising cell resource for
      future cell therapy. 

PMID- 25754207
TI  - Brain magnetic resonance imaging and outcome after hypoxic ischaemic
      encephalopathy.
AB  - OBJECTIVE: To correlate pattern of injury on neonatal brain magnetic resonance
      imaging (MRI) with outcome in infants >=36 + 0 weeks gestation with hypoxic
      ischaemic encephalopathy. METHODS: Prospective cohort study. Images were blindly
      reviewed. Children were assessed using a variety of standardised assessments.
      RESULTS: MRI brain was performed on 88 infants. Follow up was available in
      73(83%) infants. Eight of 25(32%) children with normal imaging had below normal
      assessment scores. Eight infants (12%) had isolated punctate white matter lesions
      and five of these had abnormal assessment scores. Death and cerebral palsy were
      seen only in children with imaging scores >=3 on basal ganglia/thalami (BGT)
      score or >=4 on watershed score. No developmental concerns were raised in
      3/7(43%) infants with isolated watershed injury. Ten of 13(77%) infants with
      isolated BGT injury died or developed cerebral palsy. All 23 children with
      posterior limb of the internal capsule (PLIC) injury displayed developmental
      difficulties. CONCLUSIONS: Almost one-third of infants with a normal MRI brain
      may be at risk of developmental problems. Punctate foci of white matter injury
      are common and not always benign. PLIC involvement is usually associated with
      neurological sequelae including isolated cognitive deficits. Worst outcomes are
      associated with basal ganglia injury.

PMID- 25754208
TI  - Pregnancy outcomes in autosomal dominant polycystic kidney disease: a case
      control study.
AB  - OBJECTIVES: To determine whether autosomal dominant polycystic kidney disease
      (ADPKD) is associated with adverse fetal outcomes and maternal complications.
      METHODS: We identified a cohort of 146 patients seen for pregnancy and cystic
      kidney disease at Mayo Clinic from 1975 to 2010. From this cohort, 54 patients
      met the ultrasound diagnostic criteria for ADPKD (ADPKD group), while the other
      92 patients were diagnosed as "Simple Cyst" (control group). We compared the
      fetal and maternal outcomes of pregnancy and long-term maternal prognoses between
      these two groups. RESULTS: Overall, the fetal complication rates were similar
      between the ADPKD and control groups. Rates of spontaneous abortion (15.1% versus
      14%, p = 0.77) and premature birth (11.1% versus 6.8%, p = 0.44) were comparable
      between groups, while the rate of fetal distress (3.4% versus 0.7%, p < 0.01) was
      increased in the ADPKD group. The rate of preeclampsia in the patients with
      simple cysts (2%) was similar to that of the general population. In contrast, the
      pregnant ADPKD patients had higher risks for hypertension, proteinuria, edema,
      urinary tract infection, renal dysfunction and preeclampsia during their
      pregnancies. CONCLUSION: ADPKD is associated with increased maternal
      complications during pregnancy, but only has a slight potential of increased
      rates of fetal complications.

PMID- 25754209
TI  - Author's reply to: assessing vitamin D status in infants with very low birth
      weight.

PMID- 25754210
TI  - First trimester fetal heart rate as a predictor of newborn sex.
AB  - OBJECTIVE: To predict the sex of newborns using first trimester fetal heart rate
      (FHR). METHODS: This was a retrospective review of medical records and
      ultrasounds performed between 8 and 13 weeks of gestation. Continuous variables
      were compared using Student's t-tests while categorical variables were compared
      using Chi-square test. RESULTS: We found no significant differences between 332
      (50.7%) female and 323 (49.3%) male FHRs during the first trimester. The mean FHR
      for female fetuses was 167.0 +/- 9.1 bpm and for male fetuses 167.3 +/- 10.1 bpm
      (p = 0.62). There was no significant difference in crown rump length between
      female and male fetuses (4.01 +/- 1.7 versus 3.98 +/- 1.7 cm; p = 0.78) or in
      gestational age at birth (38.01 +/- 2.1 versus 38.08 +/- 2.1 weeks; p = 0.67).
      The males were significantly heavier than females (3305.3 +/- 568.3 versus 3127.5
      +/- 579.8 g; p < 0.0001) but there were no differences in the proportion of small
      for gestational age (SGA), average for gestational age (AGA) and large for
      gestational age (LGA) infants. CONCLUSIONS: We found no significant difference
      between the female and male FHR during the first trimester in contrast to the
      prevailing lay view of females having a faster FHR. The only statistically
      significant difference was that males weighed more than female newborns.

PMID- 25754211
TI  - Anger in women treated with assisted reproductive technology (ART): effects on
      mother and newborn.
AB  - OBJECTIVE: To assess anger, as well as other negative emotions, in women who
      underwent assisted reproductive technology (ART) respect to women who conceived
      naturally, and explore the effect of anger on neonatal outcomes. METHODS: We
      recorded personal and obstetric history of the patients, neonatal weight, Apgar
      score, obstetric and neonatal complications. We performed Structural Clinical
      Interview for DSM-SCID I and II in order to assess the DSM IV axis I and axis II,
      State-Trait Anger Expression Inventory 2 (STAXI-2), the Self-rating Depression
      Scale (SDS) and Self-rating Anxiety scale (SAS). RESULTS: On the STAXI-2 scale,
      the ART group scored higher than the natural conception group on measures of
      general tendency and personality disposition to get angry. Moreover, the ART
      group women showed quite low levels of tolerance to negative environmental
      feedback. Our results further suggest that trait anger provides the most
      meaningful contribution as predictor of weight at birth. No significant
      differences were found for anxiety and depression between the two groups.
      CONCLUSIONS: Our study highlights the important role of anger during pregnancy,
      and suggests the need for further studies on both biochemical and behavioural
      patterns in larger samples of women who became pregnant by ART.

PMID- 25754212
TI  - When is the optimal time to deliver late preterm IUGR fetuses with abnormal
      umbilical artery Dopplers?
AB  - OBJECTIVE: To determine the optimal timing of delivery in late preterm
      intrauterine growth restriction (IUGR) fetuses with abnormal umbilical artery
      Doppler (UAD) indices. METHODS: A decision-analytic model was built to determine
      the optimal gestational age (GA) of delivery in a theoretic cohort of 10 000 IUGR
      fetuses with elevated UAD systolic/diastolic ratios diagnosed at 34 weeks. All
      inputs were derived from the literature. Strategies involving expectant
      management accounted for the probabilities of stillbirth, spontaneous delivery
      and induction of labor for UAD absent or reversed end-diastolic flow (AREDF) at
      each successive week. Outcomes included short- and long-term neonatal morbidity
      and mortality with quality-adjusted life years (QALYs) generated based on these
      outcomes. Base case, sensitivity analyses and a Monte Carlo simulation were
      performed. RESULTS: The optimal GA for delivery is 35 weeks, which minimized
      perinatal deaths and maximized total QALYs. Earlier delivery became optimal once
      the risk of stillbirth was threefold our baseline assumption; our model was also
      robust until the risk of AREDF at 35 weeks was half our baseline assumption,
      after which delivery at 36 weeks was preferred. Delivery at 35 weeks was the
      optimal strategy in 77% of trials in Monte Carlo multivariable sensitivity
      analysis. CONCLUSIONS: Weighing the risks of iatrogenic prematurity against the
      poor outcomes associated with AREDF, the ideal GA to deliver late preterm IUGR
      fetuses with elevated UAD indices is 35 weeks.

PMID- 25754213
TI  - Early oral feeding compared with delayed oral feeding after cesarean section: a
      meta-analysis.
AB  - AIM: The potential benefits and safety of early oral feeding (EOF) after cesarean
      section have not been well evaluated. We undertook a meta-analysis to assess
      postoperative bowel function and complications following EOF compared with
      delayed oral feeding (DOF) in women who had undergone cesarean section. METHODS:
      PubMed, EMBASE, and CENTRAL were searched to identify English language randomized
      clinical trials comparing EOF with DOF after cesarean section. The primary
      outcomes of interest were bowel motility and postoperative complications. The
      random-effect model was used to calculate pooled weighted mean differences (WMDs)
      and relative risks (RRs), with 95% confidence intervals (CIs). RESULTS: Eleven
      studies involving 1800 patients were included. The pooled results showed that EOF
      was significantly associated with the shorter time to return of bowel motility
      compared with DOF (-7.3 h for passage of flatus; -6.27 h for bowel movement; 
      8.75 h for bowel sounds). EOF was not related to increases in nausea (RR, 0.95;
      95% CI, 0.69-1.33), abdominal distension (RR, 0.68; 95% CI, 0.43-1.07), diarrhea
      (RR, 0.63; 95% CI, 0.28-1.41), mild ileus symptoms (RR, 0.82; 95% CI, 0.53-1.25)
      and vomiting (RR, 0.91; 95% CI, 0.53-1.56). CONCLUSIONS: This meta-analysis
      provides evidence that EOF after cesarean section enhances the return of bowel
      function and does not increase the risk of postoperative complications.

PMID- 25754214
TI  - Synbiotics for decreasing incidence of necrotizing enterocolitis among preterm
      neonates - a randomized controlled trial.
AB  - OBJECTIVE: To study the effect of synbiotics in reducing incidence and severity
      of necrotizing enterocolitis (NEC) among preterm neonates. METHODS: This
      randomized controlled trial conducted in a tertiary care teaching hospital, south
      India, included 220 enterally fed preterm neonates who were randomized to receive
      either synbiotics or no intervention. The synbiotic contained Lactobacillus,
      Bifidobacterium and fructo-oligosaccharide. The demographic parameters, risk
      factors for NEC and outcome including incidence of NEC, its severity, sepsis and
      mortality were evaluated. RESULTS: Multiple pregnancies, preeclampsia and
      prolonged rupture of membranes were important maternal characteristics. The
      average birth weight and gestational age of the preterm neonates was 1.4 kg and
      31 weeks, respectively. There was a 50% reduction in the incidence of NEC of all
      stages in preterm infants who received synbiotics compared to the non
      intervention group (7.4% versus 14.5%). Administration of synbiotics did not
      reduce the severity of NEC, sepsis or mortality. CONCLUSION: Enteral
      supplementation of synbiotics along with breastmilk results in a tendancy to
      decrease the incidence of NEC among preterm neonates.

PMID- 25754216
TI  - Towards a better management of complex emergencies through crisis management meta
      modelling.
AB  - Managing complex emergency situations is a challenging task, mainly due to the
      heterogeneity of the partners involved and the critical nature of such events.
      Whatever approach is adopted to support this objective, one unavoidable issue is
      knowledge management. In the context of our research project, gathering,
      formalising and exploiting all the knowledge and information about a given crisis
      situation is a critical requirement. This paper presents some research results
      concerning this specific topic: from a theoretical point of view, the generic
      dimensions of crisis characterisation are defined, while from a technical point
      of view, we describe a software solution able to collect that knowledge (based on
      meta-models and ontologies). This is used to confront the characteristics of the
      situation (context) with characteristics of the resources (relief system) in
      order to design a suitable response. Finally, an illustrative example concerning
      a crash between a tanker truck and a train is described. 

PMID- 25754215
TI  - Increased risk of hip fracture associated with dually treated HIV/hepatitis B
      virus coinfection.
AB  - HIV and hepatitis B virus (HBV) infections are each associated with reduced bone
      mineral density, but it is unclear whether HIV/HBV coinfection is associated with
      an increased risk of fracture. We determined whether dually treated HIV/HBV
      patients had a higher incidence of hip fracture compared to treated HBV
      monoinfected, antiretroviral therapy (ART)-treated HIV-monoinfected and HIV/HBV
      uninfected patients. We conducted a cohort study among 4156 dually treated
      HIV/HBV-coinfected, 2053 treated HBV-monoinfected, 96,253 ART-treated HIV
      monoinfected, and 746,794 randomly sampled uninfected persons within the US
      Medicaid populations of California, Florida, New York, Ohio and Pennsylvania
      (1999-2007). Coinfected patients were matched on propensity score to persons in
      each comparator cohort. Weighted survival models accounting for competing risks
      were used to estimate cumulative incidences and hazard ratios (HRs) with 95%
      confidence intervals (CIs) of incident hip fracture for dually treated coinfected
      patients compared to (i) HBV-monoinfected receiving nucleos(t)ide analogue or
      interferon alfa therapy, (ii) HIV-monoinfected on ART and (iii) uninfected
      persons. Dually treated coinfected patients had a higher cumulative incidence of
      hip fracture compared to ART-treated HIV-monoinfected (at 5 years: 1.70% vs
      1.24%; adjusted HR, 1.37 [95% CI, 1.03-1.83]) and uninfected (at 5 years: 1.64%
      vs 1.22%; adjusted HR, 1.35 [95% CI, 1.03-1.84]) persons. The cumulative
      incidence of hip fracture was higher among coinfected than treated HBV
      monoinfected patients (at 5 years: 0.70% vs 0.27%), but this difference was not
      statistically significant in competing risk analysis (adjusted HR, 2.62 [95% CI,
      0.92-7.51]). Among Medicaid enrollees, the risk of hip fracture was higher among
      dually treated HIV/HBV-coinfected patients than ART-treated HIV-monoinfected and
      uninfected persons.

PMID- 25754217
TI  - Negative health implications of sickle cell trait in high income countries: from
      the football field to the laboratory.
AB  - Worldwide, sickle cell trait is a highly prevalent gene carrier state. While
      generally a benign condition with a normal life expectancy, it is becoming
      increasingly clear that the sickle trait is associated with certain adverse
      outcomes. This article will focus on three of these outcomes, namely exertional
      rhabdomyolysis and sudden death, chronic renal dysfunction, and venous
      thromboembolism. In each case, the epidemiological evidence for the association
      is reviewed, together with the existing data on potential underlying mechanisms.
      Because newborn screening programmes for sickle cell anaemia also identify those
      with sickle cell trait, it is imperative that further studies determine what, if
      any, preventive measures can be taken to reduce the burden of these uncommon but
      potentially morbid complications in affected individuals. 

PMID- 25754219
TI  - Current practices of laparoscopic inguinal hernia repair: a population-based
      analysis.
AB  - PURPOSE: The selection of a laparoscopic approach for inguinal hernias varies
      among surgeons. It is unclear what is being done in actual practice. The purpose
      of this study was to report practice patterns for treatment of inguinal hernias
      among Quebec surgeons, and to identify factors that may be associated with the
      choice of operative approach. METHODS: We studied a population-based cohort of
      patients who underwent an inguinal hernia repair between 2007 and 2011 in Quebec,
      Canada. A generalized linear model was used to identify predictors associated
      with the selection of a laparoscopic approach. RESULTS: 49,657 inguinal hernias
      were repaired by 478 surgeons. Laparoscopic inguinal hernia repair (LIHR) was
      used in 8 % of all cases. LIHR was used to repair 28 % of bilateral hernias, 10 %
      of recurrent hernias, 6 % of unilateral hernias, and 4 % of incarcerated hernias.
      268 (56 %) surgeons did not perform any laparoscopic repairs, and 11 (2 %)
      surgeons performed more than 100 repairs. These 11 surgeons performed 61 % of all
      laparoscopic cases. Patient factors significantly associated with having LIHR
      included younger age, fewer comorbidities, bilateral hernias, and recurrent
      hernias. CONCLUSION: An open approach is favored for all clinical scenarios, even
      for situations where published guidelines recommend a laparoscopic approach.
      Surgeons remain divided on the best technique for inguinal hernia repair: while
      more than half never perform LIHR, the small proportion who perform many use the
      technique for a large proportion of their cases. There appears to be a gap
      between the best practices put forth in guidelines and what surgeons are doing in
      actual practice. Identification of barriers to the broader uptake of LIHR may
      help inform the design of educational programs to train those who have the desire
      to offer this technique for certain cases, and have the volume to overcome the
      learning curve.

PMID- 25754218
TI  - Foam cell-derived 4-hydroxynonenal induces endothelial cell senescence in a TXNIP
      dependent manner.
AB  - Vascular endothelial cell (VEC) senescence is considered an early event in the
      development of atherosclerotic lesions. Stressful stimuli, in particular
      oxidative stress, have been linked to premature senescence in the vasculature.
      Foam cells are a major source of reactive oxygen species and may play a role in
      the induction of VEC senescence; hence, we investigated their involvement in the
      induction of VEC senescence in a co-culture transwell system. Primary bovine
      aortic endothelial cells, exposed to the secretome of THP-1 monocyte-derived foam
      cells, were analysed for the induction of senescence. Senescence associated beta
      galactosidase activity and the expression of p16 and p21 were increased, whereas
      phosphorylated retinoblastoma protein was reduced. This senescent phenotype was
      mediated by 4-hydroxnonenal (4-HNE), a lipid peroxidation product secreted from
      foam cells; scavenging of 4-HNE in the co-culture medium blunted this effect.
      Furthermore, both foam cells and 4-HNE increased the expression of the pro
      oxidant thioredoxin-interacting protein (TXNIP). Molecular manipulation of TXNIP
      expression confirmed its involvement in foam cell-induced senescence. Previous
      studies showed that peroxisome proliferator-activated receptor (PPAR)delta was
      activated by 4-hydroalkenals, such as 4-HNE. Pharmacological interventions
      supported the involvement of the 4-HNE-PPARdelta axis in the induction of TXNIP
      and VEC senescence. The association of TXNIP with VEC senescence was further
      supported by immunofluorescent staining of human carotid plaques in which the
      expression of both TXNIP and p21 was augmented in endothelial cells.
      Collectively, these findings suggest that foam cell-released 4-HNE activates
      PPARdelta in VEC, leading to increased TXNIP expression and consequently to
      senescence. 

PMID- 25754220
TI  - Defect-induced photoluminescence blinking of single epitaxial InGaAs quantum
      dots.
AB  - Here we report two types of defect-induced photoluminescence (PL) blinking
      behaviors observed in single epitaxial InGaAs quantum dots (QDs). In the first
      type of PL blinking, the "off" period is caused by the trapping of hot electrons
      from the higher-lying excited state (absorption state) to the defect site so that
      its PL rise lifetime is shorter than that of the "on" period. For the "off"
      period in the second type of PL blinking, the electrons relax from the first
      excited state (emission state) into the defect site, leading to a shortened PL
      decay lifetime compared to that of the "on" period. This defect-induced exciton
      quenching in epitaxial QDs, previously demonstrated also in colloidal
      nanocrystals, confirms that these two important semiconductor nanostructures
      could share the same PL blinking mechanism. 

PMID- 25754221
TI  - Synthesis of a double helicene by a palladium-catalyzed cross-coupling reaction:
      structure and physical properties.
AB  - For this study, twisted pi-extended helicene 1 and double helicene 2 with a
      helicene framework were synthesized through palladium-catalyzed C-H arylation or
      Suzuki-Miyaura coupling reaction. X-ray crystallography revealed grossly twisted
      structures that were soluble in various conventional organic solvents. Optical
      properties based on UV/Vis and fluorescence spectra were measured.
      Electrochemical properties were also studied by measurements of cyclic
      voltammetry in 1 and 2, which revealed their HOMO and the LUMO energies.
      Theoretical calculation supports their HOMO and LUMO energies and molecular
      orbitals. Furthermore, a racemization process of 2 predicted that the activation
      free energy at 300 K would be 31.8 kcal mol(-1) by DFT calculation, which
      indicated the static helicity at 300 K.

PMID- 25754222
TI  - Conditioned medium from fresh and demineralized bone enhances osteoclastogenesis
      in murine bone marrow cultures.
AB  - OBJECTIVES: Osteoclasts rapidly form on the surface of bone chips at augmentation
      sites. The underlying molecular mechanism, however, is unclear. Soluble factors
      released from bone chips in vitro have a robust impact on mesenchymal cell
      differentiation. Whether these soluble factors change the differentiation of
      hematopoietic cells into osteoclasts remains unknown. METHODS:
      Osteoclastogenesis, the formation of tartrate-resistant acid phosphatase-positive
      multinucleated cells, was studied with murine bone marrow cultures exposed to
      RANKL and M-CSF, and conditioned medium from fresh (BCM) and demineralized bone
      matrix (DCM). Histochemical staining, gene and protein expression, as well as
      viability assays were performed. RESULTS: This study shows that BCM had no impact
      on osteoclastogenesis. However, when BCM was heated to 85 degrees C (BCMh), the
      number of tartrate-resistant acid phosphatase-positive multinucleated cells that
      developed in the presence of RANKL and M-CSF approximately doubled. In line with
      the histochemical observations, there was a trend that BCMh increased expression
      of osteoclast marker genes, in particular the transcription factor c-fos. The
      expression of c-fos was significantly reduced by the TGF-beta receptor I
      antagonist SB431542. DCM significantly stimulated osteoclastogenesis, independent
      of thermal processing. CONCLUSIONS: These data demonstrate that activated BCM by
      heat and DBM are able to stimulate osteoclastogenesis in vitro. These in vitro
      results support the notion that the resorption of autografts may be supported by
      as yet less defined paracrine mechanisms.

PMID- 25754223
TI  - Supramolecular synergy in the boundary lubrication of synovial joints.
AB  - Hyaluronan, lubricin and phospholipids, molecules ubiquitous in synovial joints,
      such as hips and knees, have separately been invoked as the lubricants
      responsible for the remarkable lubrication of articular cartilage; but alone,
      these molecules cannot explain the extremely low friction at the high pressures
      of such joints. We find that surface-anchored hyaluronan molecules complex
      synergistically with phosphatidylcholine lipids present in joints to form a
      boundary lubricating layer, which, with coefficient of friction MU~0.001 at
      pressures to over 100 atm, has a frictional behaviour resembling that of
      articular cartilage in the major joints. Our findings point to a scenario where
      each of the molecules has a different role but must act together with the others:
      hyaluronan, anchored at the outer surface of articular cartilage by lubricin
      molecules, complexes with joint phosphatidylcholines to provide the extreme
      lubrication of synovial joints via the hydration-lubrication mechanism. 

PMID- 25754224
TI  - To pill or not to pill in GnRH antagonist cycles: what should be the appropriate
      wash-out period?

PMID- 25754225
TI  - GnRH agonist is not required for frozen embryo transfers conducted under
      artificial hormone therapy.

PMID- 25754226
TI  - Adhesion barrier market trends.

PMID- 25754227
TI  - miR-142-3p is a novel regulator of cell viability and proinflammatory signalling
      in endometrial stroma cells.
AB  - Endometriosis is associated with severe pelvic pain and reduced fertility.
      Recently, it has been linked to a dysregulation of microRNAs (miRNAs), which are
      post-transcriptional regulators of gene expression. The functional effect of
      dysregulated miR-142-3p expression in endometrial stroma cells was investigated.
      An increased expression of miR-142-3p resulted in a significantly reduced
      expression of steroid sulfatase and interleukin-6-coreceptor gp130 as well as
      reduced interleukin-6-mediated activation of the STAT3-pathway, suggesting an
      effect of miR-142-3p both on steroid hormone- and cytokine-mediated signalling
      events. At the functional level, miR-142-3p overexpression significantly reduced
      cell viability (P <= 0.01). miR-142-3p regulation emerges as a future therapeutic
      strategy for endometriosis. 

PMID- 25754228
TI  - How to explain the role of magnetic resonance imaging on evaluating tumour
      response of osteosarcoma to neoadjuvant chemotherapy?

PMID- 25754229
TI  - Association of folate metabolism gene polymorphisms and pulmonary embolism: A
      case-control study of West-Siberian population.
AB  - INTRODUCTION: Our objective was to investigate the association between gene
      polymorphisms of folate cycle (MTHFR 677 C>T, MTHFR 1298 A>C, MTR 2756 A>G, and
      MTRR 66 A>G) and the risk of pulmonary embolism (PE) in a case-control study.
      MATERIALS AND METHODS: 177 PE patients (87 women and 90 men) were compared to a
      healthy control group (461 people, 123 women, 326 men). All of them are residents
      of Novosibirsk region. SNPs were genotyped by allele-specific PCR. RESULTS: The
      age distributions of our male and female patients were found to be significantly
      different. For men, the distribution has two maxima, whereas for women it has
      only one maximum, which is between the two. This fact stimulated us to perform a
      sex-specific analysis. No statistically significant difference has been found
      between distributions of the three genes in our PE patients and healthy controls.
      However, it was discovered that the TT genotype of MTHFR: 677 C>T polymorphism in
      men increases the risk of PE in comparison to controls. In fact, the difference
      increases in the age group over 45years. Also, AA genotype of MTRR 66 A>G
      polymorphism in women below 45years decreases the risk of PE. The sex-specific
      multiple linear regression analysis gave us estimates of the relative PE risk
      associated with MTHFR 677 C>T, F2: 20210G>A (Prothrombin), and F5: 1691G>A
      (Leiden) mutations.

PMID- 25754230
TI  - A histological and functional description of the tissue causing chronic
      postthrombotic venous obstruction.
AB  - BACKGROUND: Postthrombotic intraluminal tissue causing postthrombotic syndrome
      (PTS) has not been well described. This study defines its histological
      characteristics and assess whether tissue function evolves over time. METHODS:
      Specimens from 18 common femoral veins (CFV) from 16 patients obtained during CFV
      endovenectomy and iliocaval recanalization were examined. Phase 1 used
      hematoxylin and eosin and Masson's trichrome stains for collagen,
      immunohistochemical, and Von Kossa stains. Phase 2 examined young (<= one year)
      and mature (>=10years from acute DVT) specimens to evaluate evolution of
      endothelial function. Antibodies to four biomarkers were used to examine specific
      functions of endothelial cells lining neovessels and recanalization channels
      (RC). RESULTS: Phase 1: Specimens demonstrated 80-90% of collagen type I, 10-20%
      of collagen type III, and dystrophic calcification. Neovessels and RC were in
      close proximity to each other. Thrombus and smooth muscle cells were absent, but
      white blood cells were present. Phase 2: VEGFR2 receptor uptake was more abundant
      in neovessels than RC and more prominent in younger specimens. Neovascular,
      nonchannel cells were observed more frequently in young specimens. CD-31 was
      similar in young and mature specimens. TIE-2 and von Willebrand factor antibodies
      had greater uptake in mature specimens. CONCLUSION: Tissue causing chronic
      postthrombotic venous obstruction is predominantly type I collagen.
      Neovascularization and recanalization occur in close proximity. The biomarker for
      neovascularization and angiogenesis (VEGFR2) was more prominent in young
      specimens whereas TIE-2, a stabilizing biomarker and vWF were more frequently
      observed in mature specimens.

PMID- 25754231
TI  - Synthesis of bis-macrocyclic HCV protease inhibitor MK-6325 via intramolecular
      sp2-sp3 Suzuki-Miyaura coupling and ring closing metathesis.
AB  - A practical asymmetric synthesis of the complex fused bis-macrocyclic HCV
      protease inhibitor MK-6325 (1) is described. Through the combination of a high
      yielding and low catalyst loading ring-closing metathesis (RCM) to forge the 15
      membered macrocycle with an intramolecular sp(2)-sp(3) Suzuki-Miyaura cross
      coupling to append the 18-membered macrocycle, multikilogram access to the unique
      and challenging architecture of MK-6325 (1) has been achieved. 

PMID- 25754232
TI  - Transgenic expression of an unedited mitochondrial orfB gene product from wild
      abortive (WA) cytoplasm of rice (Oryza sativa L.) generates male sterility in
      fertile rice lines.
AB  - MAIN CONCLUSION: Over-expression of the unedited mitochondrial orfB gene product
      generates male sterility in fertile indica rice lines in a dose-dependent manner.
      Cytoplasmic male sterility (CMS) and nuclear-controlled fertility restoration are
      widespread developmental features in plant reproductive systems. In self
      pollinated crop plants, these processes often provide useful tools to exploit
      hybrid vigour. The wild abortive CMS has been employed in the majority of the
      "three-line" hybrid rice production since 1970s. In the present study, we provide
      experimental evidence for a positive functional relationship between the 1.1-kb
      unedited orfB gene transcript, and its translated product in the mitochondria
      with male sterility. The generation of the 1.1-kb unedited orfB gene transcripts
      increased during flowering, resulting in low ATP synthase activity in sterile
      plants. Following insertion of the unedited orfB gene into the genome of male
      fertile plants, the plants became male sterile in a dose-dependent manner with
      concomitant reduction of ATPase activity of F1F0-ATP synthase (complex V).
      Fertility of the transgenic lines and normal activity of ATP synthase were
      restored by down-regulation of the unedited orfB gene expression through RNAi
      mediated silencing. The genetic elements deciphered in this study could further
      be tested for their use in hybrid rice development.

PMID- 25754233
TI  - Quantification of oxide particle composition in model oxide dispersion
      strengthened steel alloys.
AB  - Oxide dispersion strengthened ferritic steels (ODS) are being considered for
      structural components of future designs of fission and fusion reactors because of
      their impressive high-temperature mechanical properties and resistance to
      radiation damage, both of which arise from the nanoscale oxide particles they
      contain. Because of the critical importance of these nanoscale phases,
      significant research activity has been dedicated to analysing their precise size,
      shape and composition (Odette et al., Annu. Rev. Mater. Res. 38 (2008) 471-503
      [1]; Miller et al., Mater. Sci. Technol. 29(10) (2013) 1174-1178 [2]). As part of
      a project to develop new fuel cladding alloys in India, model ODS alloys have
      been produced with the compositions, Fe-0.3Y2O3, Fe-0.2Ti-0.3Y2O3 and Fe-14Cr
      0.2Ti-0.3Y2O3. The oxide particles in these three model alloys have been studied
      by APT in their as-received state and following ion irradiation (as a proxy for
      neutron irradiation) at various temperatures. In order to adequately quantify the
      composition of the oxide clusters, several difficulties must be managed,
      including issues relating to the chemical identification (ranging and variable
      peak-overlaps); trajectory aberrations and chemical structure; and particle
      sizing. This paper presents how these issues can be addressed by the application
      of bespoke data analysis tools and correlative microscopy. A discussion follows
      concerning the achievable precision in these measurements, with reference to the
      fundamental limiting factors. 

PMID- 25754234
TI  - PG545 enhances anti-cancer activity of chemotherapy in ovarian models and
      increases surrogate biomarkers such as VEGF in preclinical and clinical plasma
      samples.
AB  - BACKGROUND: Despite the utility of antiangiogenic drugs in ovarian cancer,
      efficacy remains limited due to resistance linked to alternate angiogenic
      pathways and metastasis. Therefore, we investigated PG545, an anti-angiogenic and
      anti-metastatic agent which is currently in Phase I clinical trials, using
      preclinical models of ovarian cancer. METHODS: PG545's anti-cancer activity was
      investigated in vitro and in vivo as a single agent, and in combination with
      paclitaxel, cisplatin or carboplatin using various ovarian cancer cell lines and
      tumour models. RESULTS: PG545, alone, or in combination with chemotherapeutics,
      inhibited proliferation of ovarian cancer cells, demonstrating synergy with
      paclitaxel in A2780 cells. PG545 inhibited growth factor-mediated cell migration
      and reduced HB-EGF-induced phosphorylation of ERK, AKT and EGFR in vitro and
      significantly reduced tumour burden which was enhanced when combined with
      paclitaxel in an A2780 model or carboplatin in a SKOV-3 model. Moreover, in the
      immunocompetent ID8 model, PG545 also significantly reduced ascites in vivo. In
      the A2780 maintenance model, PG545 initiated with, and following paclitaxel and
      cisplatin treatment, significantly improved overall survival. PG545 increased
      plasma VEGF levels (and other targets) in preclinical models and in a small
      cohort of advanced cancer patients which might represent a potential biomarker of
      response. CONCLUSION: Our results support clinical testing of PG545, particularly
      in combination with paclitaxel, as a novel therapeutic strategy for ovarian
      cancer.

PMID- 25754235
TI  - Mutation specific functions of EGFR result in a mutation-specific downstream
      pathway activation.
AB  - BACKGROUND: Epidermal growth factor receptor (EGFR) is frequently mutated in
      various types of cancer. Although all oncogenic mutations are considered
      activating, different tumour types have different mutation spectra. It is
      possible that functional differences underlie this tumour-type specific mutation
      spectrum. METHODS: We have determined whether specific mutations in EGFR (EGFR,
      EGFRvIII and EGFR-L858R) have differences in binding partners, differences in
      downstream pathway activation (gene expression and phosphoproteins), and have
      functional consequences on cellular growth and migration. RESULTS: Using biotin
      pulldown and subsequent mass spectrometry we were able to detect mutation
      specific binding partners for EGFR. Differential binding was confirmed using a
      proximity ligation assay and/or Western Blot for the dedicator of cytokinesis 4
      (DOCK4), UDP-glucose glycoprotein glucosyltransferase 1 (UGGT1), MYC binding
      protein 2 (MYCBP2) and Smoothelin (SMTN). We also demonstrate that each mutation
      induces the expression of a specific set of genes, and that each mutation is
      associated with specific phosphorylation patterns. Finally, we demonstrate using
      stably expressing cell lines that EGFRvIII and EGFL858R display reduced growth
      and migration compared to EGFR wildtype expressing cells. CONCLUSION: Our results
      indicate that there are distinct functional differences between different EGFR
      mutations. The functional differences between different mutations argue for the
      development of mutation specific targeted therapies.

PMID- 25754236
TI  - A prospective, postmarket study with the Mguard Prime Embolic Protection Stent in
      ST-segment elevation myocardial infarction: the International MGuard Prime
      Observational Study (IMOS Prime).
AB  - AIMS: We sought to evaluate the procedural and clinical performances of the
      MGuard Prime Embolic Protection Stent (EPS) in a "real-world" population with
      acute ST-segment elevation myocardial infarction (STEMI) undergoing primary
      percutaneous coronary intervention (PPCI). METHODS AND RESULTS: Consecutive STEMI
      patients meeting the inclusion criteria and undergoing PPCI were enrolled. The
      primary endpoint was major adverse cardiac events (MACE) at 30 days, defined as
      the composite of cardiac death, myocardial infarction (Q wave and non-Q wave) or
      target lesion revascularization (PCI or coronary artery bypass graft). Secondary
      endpoints included device success, lesion success, and postprocedural reperfusion
      outcomes: thrombolysis in myocardial infarction (TIMI) flow and ST-segment
      elevation resolution (STR). A total of 97 patients (62 years, 77% men) were
      included. Symptom to cathlab time was 238 min. Device and lesion success were
      100%. Final TIMI-3 flow was achieved in 91.8%, and STR > 50% in 87% of the
      patients. MACE at 30 days was 2.2%, which consisted of one case each of target
      vessel (TV)-myocardial infarction (MI), and non-TV-MI. CONCLUSIONS: The use of
      the MGuard Prime EPS stent is feasible and safe and could be also effective in
      achieving myocardial reperfusion in STEMI patients undergoing PPCI.

PMID- 25754237
TI  - Capacitive soft strain sensors via multicore-shell fiber printing.
AB  - A new method for fabricating textile integrable capacitive soft strain sensors is
      reported, based on multicore-shell fiber printing. The fiber sensors consist of
      four concentric, alternating layers of conductor and dielectric, respectively.
      These wearable sensors provide accurate and hysteresis-free strain measurements
      under both static and dynamic conditions. 

PMID- 25754238
TI  - The History of Articulators: The Wonderful World of "Grinders," Part III.
AB  - This is the third article in a three-part series on the history of denture
      occlusal grinders. The first article reviewed the earliest attempts to "grind in"
      denture occlusion by hand manipulating simple articulators with special features
      to those more complex devices powered by hand cranks. The second article explored
      devices that were motor driven, either those with cast holders to grind the
      occlusion of processed dentures or those designed to utilize an articulator's
      condylar or incisal controls for that purpose. This article examines those
      articulators that have a rotary occlusal grinder as an essential feature.
      Additionally, this article reviews those grinding devices produced as attachments
      for popular contemporary articulators. 

PMID- 25754239
TI  - Trehalose in glycerol-free freezing extender enhances post-thaw survival of boar
      spermatozoa.
AB  - Cryopreservation of boar semen is still considered suboptimal due to lower
      fertility as compared with fresh samples when glycerol, a permeating
      cryoprotectant, is used. Trehalose is a non-permeable cryoprotectant and
      nonreducing disaccharide known to stabilize proteins and biologic membranes. The
      aim of this study was to evaluate the cryosurvival and in vitro penetrability of
      boar spermatozoa when glycerol was replaced with trehalose in a freezing
      extender. Ejaculated Berkshire semen samples were diluted in egg yolk-based
      freezing extender containing glycerol (100 mM) or trehalose (0, 50, 100, 150, 200
      and 250 mM) and cryopreserved using a straw freezing procedure. Thawed samples
      were analyzed for motility, viability, mitochondrial membrane potential (MMP),
      and acrosome integrity. In experiment 2, penetrability of spermatozoa
      cryopreserved with 100 mM glycerol or trehalose was examined. Replacement of
      cryoprotectant glycerol (100 mM) with trehalose had no effect on sperm viability,
      but replacing it with 100 mM trehalose improved motility, MMP and acrosome
      integrity significantly. Sperm motility and MMP were considerably higher in 100
      mM trehalose, whereas the acrosome integrity was substantially higher in 100-250
      mM trehalose. The in vitro penetration rate was also significantly higher in
      spermatozoa cryopreserved with trehalose (61.3%) than in those cryopreserved with
      glycerol (43.6%). In conclusion, 100 mM non-permeable trehalose can be used to
      replace glycerol, a permeating cryoprotectant, for maintenance of better post
      thaw quality of boar spermatozoa. 

PMID- 25754240
TI  - Androgens promote the acquisition of maturation competence in bovine oocytes.
AB  - Recent studies in mice suggest that androgens are important for normal follicle
      development. However, there have been few reports concerning the action of
      androgens in the growth of oocytes from large animals. The purpose of this study
      was to determine the roles of androgens in bovine oocyte growth in vitro. Oocyte
      granulosa cell complexes (OGCs) collected from 0.4-0.7 mm early antral follicles
      were cultured for 14 days with 17beta-estradiol (E2) and a non-aromatizable
      androgen, dihydrotestosterone (DHT). We also examined the ability of an androgen
      receptor (AR) inhibitor, hydroxyflutamide, to antagonize the effect of androgens
      on the oocytes. During growth culture, the OGC structures collapsed in the medium
      with DHT alone, while in the presence of E2, the OGC structures were maintained.
      In the medium with both androgens and E2, the mean diameter of oocytes was
      increased from 95 MUm to around 120 MUm, larger than those grown with E2 alone
      (115 MUm). Also in the maturation culture, oocytes grown with androgens (A4 or
      DHT) and E2 showed higher percentages of metaphase II oocytes (63% or 69%,
      respectively) than those grown with E2 alone (32%). Moreover, these maturation
      rates were decreased by hydroxyflutamide in a dose-dependent manner.
      Immunostaining showed that ARs were expressed in oocytes and granulosa cells in
      early antral follicles, and the nuclei of granulosa cells showed intense AR
      expression. In conclusion, although E2 supports the OGC structure, additional
      androgens promote oocyte growth and their acquisition of meiotic competence via
      AR during in vitro growth culture. 

PMID- 25754241
TI  - Outcomes after ABO-incompatible heart transplantation in adults: A registry
      study.
AB  - BACKGROUND: In the past, ABO incompatibility was considered an absolute
      contraindication to heart transplantation (HT) in adults. Advances in ABO
      incompatible HT in pediatric patients and ABO-incompatible abdominal
      transplantation in adult patients have led to clinical exploration of intentional
      ABO-incompatible HT in adults. However, it is not well known how outcomes in ABO
      incompatible adult heart transplant recipients compare with outcomes in ABO
      compatible recipients. METHODS: We analyzed International Society for Heart and
      Lung Transplantation transplant registry data from heart donors and recipients
      >=18 years old at the time of transplant for HT performed between 1988 and 2011.
      We compared baseline characteristics and post-transplant outcomes in ABO
      incompatible and ABO-compatible HT. Death or retransplantation was the composite
      primary end-point. RESULTS: Among 76,663 adult patients undergoing HT between
      1988 and June 30, 2011, 94 ABO-incompatible heart transplants were performed. The
      incidence of death or retransplantation in the ABO-incompatible group was higher
      than in the ABO-compatible group: 21% vs 9% at 30 days (hazard ratio = 2.38, p <
      0.001) and 36% vs 19% at 1 year after transplant. However, ABO-incompatible
      grafts surviving past the first year after transplant had a similar incidence of
      failure compared with the ABO-compatible group. After 2005, the rate ABO
      incompatible HT in adults increased, likely as a result of planned, intentional
      (rather than accidental) ABO-incompatible HT. In this group of patients, short
      term and long-term incidence of death or retransplantation was similar to ABO
      compatible recipients (p = 0.822): 7% at 30 days and 19% at 1 year after
      transplantation. CONCLUSIONS: We found no difference in incidence of death or
      retransplantation between ABO-compatible and ABO-incompatible HT in patients who
      underwent transplantation after 2005.

PMID- 25754242
TI  - The truth about lying.
AB  - The standard view in social science and philosophy is that lying does not require
      the liar's assertion to be false, only that the liar believes it to be false. We
      conducted three experiments to test whether lying requires falsity. Overall, the
      results suggest that it does. We discuss some implications for social scientists
      working on social judgments, research on lie detection, and public moral
      discourse. 

PMID- 25754243
TI  - Comparison of primary tumour volumes delineated on four-dimensional computed
      tomography maximum intensity projection and (18) F-fluorodeoxyglucose positron
      emission tomography computed tomography images of non-small cell lung cancer.
AB  - INTRODUCTION: The study aims to compare the positional and volumetric differences
      of tumour volumes based on the maximum intensity projection (MIP) of four
      dimensional CT (4DCT) and (18) F-fluorodexyglucose ((18) F-FDG) positron emission
      tomography CT (PET/CT) images for the primary tumour of non-small cell lung
      cancer (NSCLC). METHODS: Ten patients with NSCLC underwent 4DCT and (18) F-FDG
      PET/CT scans of the thorax on the same day. Internal gross target volumes (IGTVs)
      of the primary tumours were contoured on the MIP images of 4DCT to generate
      IGTVMIP . Gross target volumes (GTVs) based on PET (GTVPET ) were determined with
      nine different threshold methods using the auto-contouring function. The
      differences in the volume, position, matching index (MI) and degree of inclusion
      (DI) of the GTVPET and IGTVMIP were investigated. RESULTS: In volume terms,
      GTVPET 2.0 and GTVPET 20% approximated closely to IGTVMIP with mean volume ratio
      of 0.93 +/- 0.45 and 1.06 +/- 0.43, respectively. The best MI was between IGTVMIP
      and GTVPET 20% (0.45 +/- 0.23). The best DI of IGTVMIP in GTVPET was IGTVMIP in
      GTVPET 20% (0.61 +/- 0.26). CONCLUSIONS: In 3D PET images, the GTVPET contoured
      by standardised uptake value (SUV) 2.0 or 20% of maximal SUV (SUVmax )
      approximate closely to the IGTVMIP in target size, while the spatial mismatch is
      apparent between them. Therefore, neither of them could replace IGTVMIP in
      spatial position and form. The advent of 4D PET/CT may improve the accuracy of
      contouring the perimeter for moving targets.

PMID- 25754244
TI  - Ethylene mediates brassinosteroid-induced stomatal closure via Galpha protein
      activated hydrogen peroxide and nitric oxide production in Arabidopsis.
AB  - Brassinosteroids (BRs) are essential for plant growth and development; however,
      whether and how they promote stomatal closure is not fully clear. In this study,
      we report that 24-epibrassinolide (EBR), a bioactive BR, induces stomatal closure
      in Arabidopsis (Arabidopsis thaliana) by triggering a signal transduction pathway
      including ethylene synthesis, the activation of Galpha protein, and hydrogen
      peroxide (H(2)O(2)) and nitric oxide (NO) production. EBR initiated a marked rise
      in ethylene, H(2)O(2) and NO levels, necessary for stomatal closure in the wild
      type. These effects were abolished in mutant bri1-301, and EBR failed to close
      the stomata of gpa1 mutants. Next, we found that both ethylene and Galpha mediate
      the inductive effects of EBR on H(2)O(2) and NO production. EBR-triggered
      H(2)O(2) and NO accumulation were canceled in the etr1 and gpa1 mutants, but were
      strengthened in the eto1-1 mutant and the cGalpha line (constitutively
      overexpressing the G protein alpha-subunit AtGPA1). Exogenously applied H(2)O(2)
      or sodium nitroprusside (SNP) rescued the defects of etr1-3 and gpa1 or etr1 and
      gpa1 mutants in EBR-induced stomatal closure, whereas the stomata of eto1
      1/AtrbohF and cGalpha/AtrbohF or eto1-1/nia1-2 and cGalpha/nia1-2 constructs had
      an analogous response to H(2)O(2) or SNP as those of AtrbohF or Nia1-2 mutants.
      Moreover, we provided evidence that Galpha plays an important role in the
      responses of guard cells to ethylene. Galpha activator CTX largely restored the
      lesion of the etr1-3 mutant, but ethylene precursor ACC failed to rescue the
      defects of gpa1 mutants in EBR-induced stomatal closure. Lastly, we demonstrated
      that Galpha-activated H(2)O(2) production is required for NO synthesis. EBR
      failed to induce NO synthesis in mutant AtrbohF, but it led to H(2)O(2)
      production in mutant Nia1-2. Exogenously applied SNP rescued the defect of
      AtrbohF in EBR-induced stomatal closure, but H(2)O(2) did not reverse the lesion
      of EBR-induced stomatal closure in Nia1-2. Together, our results strongly suggest
      a signaling pathway in which EBR induces ethylene synthesis, thereby activating
      Galpha, and then promotes AtrbohF-dependent H(2)O(2) production and subsequent
      Nia1-catalyzed NO accumulation, and finally closes stomata.

PMID- 25754245
TI  - Assessing subject-related variations of the Ocular Response Analyzer parameter
      calculation.
AB  - BACKGROUND: The aim was to study the relationships between the output parameters
      of the Ocular Response Analyzer (ORA) and those calculated from the raw ORA data
      and to ascertain the subject-related variations of ORA parameter calculation
      procedures. METHOD: Six subjects were recruited for a prospective study. Up to 32
      measurements by ORA were performed in series on the dominant eye of each subject.
      A relationship was examined between Goldmann-correlated intraocular pressure
      values (IOPg) obtained from the standard ORA output and IOPg' calculated from raw
      ORA data with a custom-written procedure. The same analysis was carried out for
      the parameters of corneal hysteresis (CH and CH'). Data and statistical analysis
      included Epanechnikov kernel smoothing, orthogonal linear regression, hypothesis
      testing and bootstrap techniques. RESULTS: The group average (mean +/- standard
      deviation) IOPg and CH values were 11.6 +/- 1.8 mmHg and 10.7 +/- 1.7 mmHg,
      respectively. A strong correlation was found between IOPg and IOPg' and also
      between CH and CH' parameters. There was a significant (Behrens-Fisher test, p <
      0.001) difference between subjects for both IOPg and CH calculations, in terms of
      the regression slope parameter. CONCLUSIONS: Subject-related variations of ORA
      parameter calculation were demonstrated. This could indicate that currently
      employed estimators of IOP parameters include unreported algorithmic procedures
      that may lead to biased results.

PMID- 25754246
TI  - Increasing water-use efficiency directly through genetic manipulation of stomatal
      density.
AB  - Improvement in crop water-use efficiency (WUE) is a critical priority for regions
      facing increased drought or diminished groundwater resources. Despite new tools
      for the manipulation of stomatal development, the engineering of plants with high
      WUE remains a challenge. We used Arabidopsis epidermal patterning factor (EPF)
      mutants exhibiting altered stomatal density to test whether WUE could be improved
      directly by manipulation of the genes controlling stomatal density. Specifically,
      we tested whether constitutive overexpression of EPF2 reduced stomatal density
      and maximum stomatal conductance (gw(max) ) sufficiently to increase WUE. We
      found that a reduction in gw(max) via reduced stomatal density in EPF2
      overexpressing plants (EPF2OE) increased both instantaneous and long-term WUE
      without altering significantly the photosynthetic capacity. Conversely, plants
      lacking both EPF1 and EPF2 expression (epf1epf2) exhibited higher stomatal
      density, higher gw(max) and lower instantaneous WUE, as well as lower (but not
      significantly so) long-term WUE. Targeted genetic modification of stomatal
      conductance, such as in EPF2OE, is a viable approach for the engineering of
      higher WUE in crops, particularly in future high-carbon-dioxide (CO2 )
      atmospheres. 

PMID- 25754247
TI  - FSH regulates fat accumulation and redistribution in aging through the
      Galphai/Ca(2+)/CREB pathway.
AB  - Increased fat mass and fat redistribution are commonly observed in aging
      populations worldwide. Although decreased circulating levels of sex hormones,
      androgens and oestrogens have been observed, the exact mechanism of fat
      accumulation and redistribution during aging remains obscure. In this study, the
      receptor of follicle-stimulating hormone (FSH), a gonadotropin that increases
      sharply and persistently with aging in both males and females, is functionally
      expressed in human and mouse fat tissues and adipocytes. Follicle-stimulating
      hormone was found to promote lipid biosynthesis and lipid droplet formation; FSH
      could also alter the secretion of leptin and adiponectin, but not hyperplasia, in
      vitro and in vivo. The effects of FSH are mediated by FSH receptors coupled to
      the Galphai protein; as a result, Ca(2+) influx is stimulated, cAMP-response
      element-binding protein is phosphorylated, and an array of genes involved in
      lipid biosynthesis is activated. The present findings depict the potential of FSH
      receptor-mediated lipodystrophy of adipose tissues in aging. Our results also
      reveal the mechanism of fat accumulation and redistribution during aging of males
      and females.

PMID- 25754248
TI  - Two new beta+ -thalassemia mutation [beta -56 (G -> C); HBBc. -106 G -> C] and
      [beta -83 (G -> A); HBBc. -133 G -> A] described among the Tunisian population.
AB  - OBJECTIVES: Different thalassemia mutations have been reported in various ethnic
      groups and geographical regions in Tunisia. In the present study, we have
      investigated two rare beta(+) -thalassemia mutations, that have not previously
      been reported in the Tunisian population [beta -56 (G > C); HBBc. -106 G > C] and
      [beta -83 (G > A); HBBc. -133 G > A]. METHODS: The whole beta-globin gene was
      directly sequenced, and haplotype analysis was conducted through a PCR/RFLP
      method. RESULTS: Two new mutations were identified for the first time in Tunisia.
      They are located within the promoter region of beta-globin gene at position -56
      (G > C) and -83 (G > A). Linkage analysis using beta-globin gene cluster
      haplotypes showed that these two mutations were associated with Mediterranean
      beta-haplotype IX [- + - + + + +] and framework 2 (FW2) [CCTCT]. CONCLUSIONS: The
      two newly described mutations lead to the beta(+) -thalassemia among Tunisian
      patients. The haplotype analysis and framework assignment have helped to identify
      the chromosomal background associated with these mutations, and determine their
      origin and spread.

PMID- 25754249
TI  - Current Status and Future Prospects to Achieve Foot-and-Mouth Disease Eradication
      in South America.
AB  - South America has a favourable position with respect to foot-and-mouth disease
      (FMD) compared with other FMD-affected regions due to the elimination of endemic
      clinical presentation of the disease. South America has reached the final stage
      of control and aims to eradicate the disease in the region under the provisions
      of the Hemispheric Program for the Eradication of FMD 2011-2020 (PHEFA). This
      programme aims at bringing eradication to completion, thereby eliminating the
      pool of foot-and-mouth disease genotypes active in South America. This plan
      includes a regional political agreement that provides strategies and technical
      guidelines for the eradication of foot-and-mouth disease from South America. It
      incorporates knowledge and experience regarding the disease's history and its
      connection with the different production systems, animal movement and trade. The
      Pan American Foot and Mouth Disease Center has led the control and eradication
      programmes, providing the framework for designing national and subregional
      programmes that have led to significant progress in controlling the disease in
      South America. The current situation is the result of several factors, including
      the proper implementation of a national control programmes, good veterinary
      infrastructure in most countries and public-private participation in the process
      of eradicating the disease. Notwithstanding the favourable health status, there
      are significant challenges for the goal of eradication. At this stage, South
      American countries should enhance their surveillance strategies particularly
      through the use of target or risk-based surveys that contribute to increase the
      degree of sensitivity in the search for viral circulation in the context of
      absence of clinical occurrence of FMD.

PMID- 25754250
TI  - Effective learning and retention of braille letter tactile discrimination skills
      in children with developmental dyslexia.
AB  - Children with developmental dyslexia (DD) may differ from typical readers in
      aspects other than reading. The notion of a general deficit in the ability to
      acquire and retain procedural ('how to') knowledge as long-term procedural memory
      has been proposed. Here, we compared the ability of elementary school children,
      with and without reading difficulties (DD, typical readers), to improve their
      tactile discrimination with practice and tested the children's ability to retain
      the gains. Forty 10-11-year-olds practiced the tactile discrimination of four
      braille letters, presented as pairs, while blindfolded. In a trial, participants
      were asked to report whether the target stimuli were identical or different from
      each other. The structured training session consisted of six blocks of 16 trials
      each. Performance was re-tested at 24 hours and two weeks post-training. Both
      groups improved in speed and in accuracy. In session 1, children with DD started
      as significantly less accurate and were slower than the typical readers but
      showed rapid learning and successfully closed the gap. Only two children with DD
      failed to benefit from training and were not included in subsequent data
      analyses. At 24 hours post-training both groups showed effective retention of the
      gains in speed and accuracy. Importantly, children with DD were able to retain
      the gains in speed and accuracy, over a two-week interval as effectively as
      typical readers. Thus, children with DD were as effective in the acquisition and
      retention of tactile discrimination of braille letters as typical readers of the
      same age. The results do not support the notion of a general procedural learning
      disability in DD.

PMID- 25754251
TI  - Combination of automated solid-phase and enzymatic oligosaccharide synthesis
      provides access to alpha(2,3)-sialylated glycans.
AB  - A synthetic strategy combining automated solid-phase chemical synthesis and
      enzymatic sialylation was developed to access alpha(2,3)-sialylated glycans. 

PMID- 25754253
TI  - All trans retinoic acid (ATRA) mediated modulation of N-methyl D-aspartate
      receptor (NMDAR) and Kruppel like factor 11 (KLF11) expressions in the mitigation
      of ethanol induced alterations in the brain.
AB  - BACKGROUND: Damaging effects that chronic ethanol exposure causes to the brain
      and the neurons are well documented. Ethanol and its toxic metabolites increase
      the oxidative stress in brain. Chronic exposure to ethanol leads to upregulation
      of N-methyl D-aspartate receptors (NMDAR) and also activates Kruppel like factor
      11 (KLF11) mediated death cascade and thereby neurodegeneration. OBJECTIVE:
      Ethanol depletes vitamin A stores. But supplementation of vitamin A exacerbates
      ethanol induced toxicity since alcohol and its metabolites are competitive
      inhibitors of the enzymes involved in the metabolism of vitamin A. Hence, in this
      study we investigated the impact of co-administration of ethanol and all trans
      retinoic acid (ATRA), active metabolite of vitamin A, on ethanol induced
      alterations to the brain. MATERIALS AND METHODS: Male Sprague Dawley rats,
      adolescent, were grouped as follows and maintained for 90 days. I - Control, II -
      Ethanol (4 g/kg b.w.), III - ATRA (100 ug/kg b.w.), IV - Ethanol (4 g/kg b.w.),
      +ATRA (100 ug/kg b.w.). Oxidative stress and the mRNA expression of various
      receptors for the neurotransmitter involved in glutamergic, serotonergic and
      gabaergic pathways were studied in the brain homogenate. RESULTS: Ethanol
      treatment was shown to decrease brain weight and it was increased on ATRA
      treatment. Increase in oxidative stress due to ethanol treatment was also brought
      down on ATRA administration. Ethanol induced upregulation of NMDAR and KLF11 was
      also downregulated on ATRA supplementation. The alterations in the levels of
      neurotransmitters and the expression of their receptors due to ethanol treatment
      also were ameliorated on ATRA supplementation. CONCLUSION: Our results show that
      ATRA supplementation mitigates the ethanol induced alterations in the brain by
      reducing oxidative stress in the brain with concurrent suppression of NMDAR and
      KLF11 expression leading to enhanced catabolism of neurotransmitters.

PMID- 25754252
TI  - Metabolic syndrome and cerebrovascular impairment in Alzheimer's disease.
AB  - OBJECTIVE: Metabolic Syndrome (MeS) has inconstantly been associated with
      cognitive impairment. The aim of this study was to investigate the influence of
      MeS on cerebrovascular reactivity and the possible consequences on cognitive
      impairment in patients with Alzheimer's disease (AD). METHODS: A total of 162 AD
      patients were enrolled and grouped depending on the presence/absence of MeS. An
      ultrasound assessment of the neck vessels was performed to evaluate common
      carotid artery intima-media thickness (IMT). Cerebral hemodynamics was assessed
      by the transcranial Doppler-based breath-holding index (BHI) test. The
      relationship between BHI and MeS was explored first with a nested binary logistic
      model and then with a general linear model/adjusted model. Both models were
      corrected for sex, age, education, BMI, smoking attitude, and IMT treated as
      covariates. RESULTS: Pathologic BHI values were significantly more frequent among
      patients with MeS (risk ratio (RR):1.477; 95% CI: 1.177-1.848). MeS significantly
      improved the prediction of a pathologic BHI in the binary logistic model (odds
      ratio (OR):11.64; 95% CI: 1.001-135.304; p < 0.05). Moreover, AD patients
      affected by MeS had significantly lower mean Mini-Mental State Evaluation values
      than the unaffected ones (16.06; 95% CI: 14.96-17.15 vs 17.79; 95% CI: 17.05
      18.53; p < 0.0001). CONCLUSIONS: Our data show an association between the
      presence of MeS and cerebral hemodynamics. The possibility that a cluster of
      potentially treatable vascular risk factors may influence AD patients' prognosis
      deserves consideration.

PMID- 25754254
TI  - Effects of music on psychophysiological responses and opioid dosage in patients
      undergoing total knee replacement surgery.
AB  - AIM: The present authors examined the effects of listening to music on
      psychophysiological parameters (blood pressure, heart rate, and respiratory rate)
      during preoperative and postoperative days and determined whether listening to
      music could lower pain intensity and opioid dosage during postoperative days in
      patients who underwent total knee replacements. METHODS: This was a two group
      repeated measures design for 30 subjects aged 53-85 years who were scheduled for
      total knee replacement. Subjects were randomly assigned to either a music group
      or a control group. Psychophysiological parameters were obtained from patients'
      monitors. A visual analog scale was used to assess postoperative pain. Opioid
      dosage was recorded and converted to standardized units. Mann-Whitney U-test and
      generalized estimating equation analysis were used to compare groups. RESULTS:
      Respiratory rates while in the surgical waiting area were lower for the music
      group than for the control group (P = 0.02). There was no significant difference
      between these groups for blood pressure, heart rate, pain intensity, or opioid
      dosage. However, a within-group comparison showed that systolic blood pressure in
      the music group was significantly and consistently decreased during postoperative
      recovery (Wald = 9.21, P = 0.007). CONCLUSION: These results suggest that
      listening to music stabilized systolic blood pressure in patients during
      postoperative recovery. However, the effects of music on psychophysiological
      parameters, pain intensity, and opioid dosage in a surgical setting require
      further research.

PMID- 25754255
TI  - The Effect of Taper Angle and Spline Geometry on the Initial Stability of
      Tapered, Splined Modular Titanium Stems.
AB  - Design parameters affecting initial mechanical stability of tapered, splined
      modular titanium stems (TSMTSs) are not well understood. Furthermore, there is
      considerable variability in contemporary designs. We asked if spline geometry and
      stem taper angle could be optimized in TSMTS to improve mechanical stability to
      resist axial subsidence and increase torsional stability. Initial stability was
      quantified with stems of varied taper angle and spline geometry implanted in a
      foam model replicating 2cm diaphyseal engagement. Increased taper angle and a
      broad spline geometry exhibited significantly greater axial stability (+21%-269%)
      than other design combinations. Neither taper angle nor spline geometry
      significantly altered initial torsional stability. 

PMID- 25754256
TI  - Complication, Survival, and Reoperation Rates Following Girdlestone Resection
      Arthroplasty.
AB  - Failed hip arthroplasty patients unsuitable for reimplantation may be offered
      Girdlestone resection arthroplasty (GRA). The purpose of this study was to detail
      complication and failure rates following GRA. Our results show that 66% (25/38),
      34% (13/38), and 76% (29/38) of GRA patients experienced minor, major, and
      overall complications, respectively. Within 90 days of surgery, three patients
      required additional surgery and four died. Reoperation or death occurred an
      average of 26.3 (SD=3.5) and 55.6 (SD=76) months after surgery, respectively.
      Male gender and increasing comorbidity significantly predicted higher reoperation
      and mortality rates, P=0.01 and P=0.04, respectively. Complication and mortality
      rates following GRA are among the highest reported succeeding elective hip
      surgery for non-traumatic etiology. 

PMID- 25754257
TI  - Three Year RSA Evaluation of Vitamin E Diffused Highly Cross-linked Polyethylene
      Liners and Cup Stability.
AB  - Vitamin E diffusion into highly cross-linked polyethylene (E-XLPE) is a method
      for enhancing oxidative stability of acetabular liners. The purpose of this study
      was to evaluate in vivo penetration of E-XLPE using radiostereometric analysis
      (RSA). Eighty-four hips were recruited into a prospective 10-year RSA. This is
      the first evaluation of the multicenter cohort after 3-years. All patients
      received E-XLPE liners (E1, Biomet) and porous-titanium coated cups (Regenerex,
      Biomet). There was no difference (P=0.450) in median femoral head penetration
      into the E-XLPE liners at 3-years comparing cobalt-chrome heads (-0.028mm; inter
      quartile range (IQR) - 0.065 to 0.047) with ceramic heads (-0.043mm, IQR -
      0.143to0.042). The 3-year follow-up indicates minimal E-XLPE liner penetration
      regardless of head material and minimal early cup movement. 

PMID- 25754258
TI  - Metabolomics integrated elementary flux mode analysis in large metabolic
      networks.
AB  - Elementary flux modes (EFMs) are non-decomposable steady-state pathways in
      metabolic networks. They characterize phenotypes, quantify robustness or identify
      engineering targets. An EFM analysis (EFMA) is currently restricted to medium
      scale models, as the number of EFMs explodes with the network's size. However,
      many topologically feasible EFMs are biologically irrelevant. We present
      thermodynamic EFMA (tEFMA), which calculates only the small(er) subset of
      thermodynamically feasible EFMs. We integrate network embedded thermodynamics
      into EFMA and show that we can use the metabolome to identify and remove
      thermodynamically infeasible EFMs during an EFMA without losing biologically
      relevant EFMs. Calculating only the thermodynamically feasible EFMs strongly
      reduces memory consumption and program runtime, allowing the analysis of larger
      networks. We apply tEFMA to study the central carbon metabolism of E. coli and
      find that up to 80% of its EFMs are thermodynamically infeasible. Moreover, we
      identify glutamate dehydrogenase as a bottleneck, when E. coli is grown on
      glucose and explain its inactivity as a consequence of network embedded
      thermodynamics. We implemented tEFMA as a Java package which is available for
      download at https://github.com/mpgerstl/tEFMA. 

PMID- 25754259
TI  - Origin of fasciculations in root lesions.
AB  - OBJECTIVE: Fasciculations are occasionally observed in root lesions, but their
      site of origin is uncertain. METHODS: We studied the origin of fasciculations
      (FPs) in consecutive patients with mild chronic L5 root lesions, excluding
      peripheral nerve lesion. We used a novel technique of double-EMG needle
      recording, in which each needle was placed in the territory of separate motor
      units. With this technique the observation of synchronous FPs implies an origin
      proximal to distal axonal branching. RESULTS: FPs were found in 13% of 84
      consecutive patients with mild chronic L5 root lesions. In 25% they were
      synchronous in different motor units. CONCLUSIONS: We suggest that in mild L5
      root lesions most FPs have an origin at distal branches but some FPs originate
      proximally (25%), possibly at the site of nerve compression. SIGNIFICANCE: The
      proximal site of compression and more distal sites may both initiate
      fasciculation potentials in proximal root lesions.

PMID- 25754260
TI  - The StartReact effect in tasks requiring end-point accuracy.
AB  - OBJECTIVE: Fast and accurate movements are often performed in response to a
      sensory signal. In reaction time tasks, execution of open loop movements is
      speeded up when a startling auditory stimulus (SAS) is applied together with the
      imperative signal (IS). In this study, we examined the effects of a SAS on the
      performance of a task that demands accuracy. METHODS: Nine subjects were asked to
      move a monitored pen to a target point located in a table at a fixed angular
      distance of 30 degrees from a start point. The target was a spot of three
      possible diameters: 5, 10, and 20mm. Finger force for pen holding, pen tip
      pressure against the table and kinematic variables of the forearm movement were
      measured for three conditions: control, SAS delivered at IS (SAS-IS trials) and
      SAS delivered during movement execution (SAS-MOV trials). RESULTS: Two movement
      phases could be identified in the movement trajectory and force profile. The
      first phase, ballistic, was significantly shortened in SAS-MOV trials, with
      earlier and larger peak velocity and peak force with respect to control trials.
      The second phase, slow approach to target, was longer in SAS-IS trials but not in
      SAS-MOV trials. Accuracy was maintained throughout all conditions and stimulation
      modes. CONCLUSIONS: A SAS speeds up only the first (ballistic) part of the
      movement in an accuracy task. Slower target approach compensates for the
      accelerated initial movement. No changes in the last part of the movement are
      seen when a SAS is delivered after movement onset. SIGNIFICANCE: The StartReact
      effect is restricted to the onset of a complex movement, when muscles are
      activated in a ballistic mode, without feedback.

PMID- 25754261
TI  - EEG correlates of a mental arithmetic task in patients with first episode
      schizophrenia and schizoaffective disorder.
AB  - OBJECTIVE: To evaluate the spectral power of the cortical bands in patients with
      first episode schizophrenia and schizoaffective disorder at rest and during the
      performance of a mental arithmetic task. METHODS: We analyzed EEG spectral power
      (SP) in the resting state and subsequently while counting down from 200 in steps
      of 7, in 32 first episode schizophrenia patients (SZ), 32 patients with first
      episode schizoaffective disorder (SA) and healthy controls (HC, n=40). Behavioral
      parameters such as accuracy and counting speed were also evaluated. RESULTS: Both
      SZ and SA patients were slower in counting than HC, no difference was obtained in
      the accuracy and counting speed in the patient groups. In the resting state
      patients showed elevated midline theta power, off-midline anterior beta 2 power
      and decreased central/posterior alpha power. The SA group occupied an
      intermediate position between the schizophrenia patients and controls. In task
      performance patients lacked a typical increase of midline theta, left anterior
      beta 2, and anterior gamma power; however, schizoaffective patients demonstrated
      a growing trend of power in the gamma band in left anterior off-midline sites
      similar to HC. Moreover, alpha power was less inhibited in schizoaffective
      patients and more pronounced in schizophrenia patients indicating distinct
      inhibitory mechanisms in these psychotic disorders. CONCLUSIONS: Patients with SA
      demonstrate less alteration in the spectral power of bands at rest than SZ, and
      present spectral power changes during cognitive task performance close to the
      controls. SIGNIFICANCE: Our study contributes to the present evidence on the
      neurophysiological distinction between schizophrenia and schizoaffective
      disorder.

PMID- 25754262
TI  - Biodistribution of Evans blue in an orthotopic AY-27 rat bladder urothelial cell
      carcinoma model: implication for the improved diagnosis of non-muscle-invasive
      bladder cancer (NMIBC) using dye-guided white-light cystoscopy.
AB  - OBJECTIVES: To investigate the possibility of using Evans blue (EB) as a novel
      diagnostic tool to detect bladder tumours with white-light (WL) cystoscopy, in
      this preclinical study we examine the biodistribution of EB in the different
      layers (urothelium, submucosa, muscle) of a normal rat bladder and a rat bladder
      bearing a malignant urothelium composed of syngeneic AY-27 tumour cells.
      MATERIALS AND METHODS: EB was instilled into both normal as well as tumour
      bearing rat bladders. After instillation, bladders were removed and snap frozen
      in liquid nitrogen. The distribution of EB in the different layers was quantified
      using fluorescence microscopy. To gain more insight into the mechanism underlying
      the selective accumulation of EB in tumour tissue, bladder sections were prepared
      for ultrastructural investigations by means of transmission electron microscopy
      (TEM). In addition, we also examined the expression of E-cadherin, claudin-1 and
      desmoglein-1 by immunohistochemistry to study the integrity of the bladder wall,
      as these molecules are key constituents of adherens junctions, tight junctions
      and desmosomes, respectively. RESULTS: In most cases, the accumulation of EB in
      malignant bladders was substantially higher than in healthy bladders, at least
      when 1 mm EB instillations were used. In case of a 1 mm EB instillation for 2 h,
      the EB-associated fluorescence in malignant urothelial tissue was 55-times higher
      than the fluorescence found in normal urothelium. Ultrastructurally, malignant
      tissue displayed wider intercellular spaces and a decreased number of cell
      junction components compared with normal tissue, pointing to defects in the
      urothelial barrier. There were no differences in the expression of E-cadherin,
      whereas desmoglein-1 staining was stronger in the membranes of healthy bladder
      urothelium compared with tumour tissue. Claudin-1 expression was negative in all
      samples tested. CONCLUSION: EB is selectively taken up by tumour tissue after
      intravesical instillations in rats bearing bladder tumours. The lower expression
      of desmoglein-1 in tumour samples, together with the reduced presence of
      desmosomes seen with TEM, likely imply that desmosomes play an important role in
      the ultrastructural differences between healthy rat urothelium and tumour tissue,
      and secondary to that, to the differential uptake of EB in both tissues. We
      consider that our findings could be useful for future clinical developments in
      the field of diagnostics for bladder cancer.

PMID- 25754263
TI  - Effects of changing exposure to neighbourhood greenness on general and mental
      health: A longitudinal study.
AB  - Green neighbourhood environments have been associated with physical and
      psychological wellbeing in adults. Access to greenness is potentially more
      important in vulnerable subgroups. In this study based on longitudinal survey
      data from southern Sweden the cohort was divided into prognostic groups for good
      self-reported general (n=8891) and mental (n=9444) health. We used independent
      survey data to assess perceived neighbourhood greenness in 1km(2) areas, and
      estimated effects of changing exposure longitudinally stratified by prognostic
      group. The overall effect on health was small and statistically uncertain (for
      general health OR 1.04, 95% CI 0.98-1.10, for mental health OR 1.07, 95% CI 1.00
      1.14). A more beneficial effect of increased greenness was indicated among
      subjects with lowest prognostic of good general health (OR 1.24, 95% CI 1.01
      1.52). The study provided only weak evidence for beneficial effects of increased
      neighbourhood greenness triggered by changing residence. It seems that altered
      life circumstances, e.g. changed civil or socioeconomic status that often trigger
      a decision to move, are also the key determinants of the health consequences of
      changing residence.

PMID- 25754264
TI  - How community physical, structural, and social stressors relate to mental health
      in the urban slums of Accra, Ghana.
AB  - Urban health in developing counties is a major public health challenge. It has
      become increasingly evident that the dialog must expand to include mental health
      outcomes, and to shift focus to the facets of the urban environment that shape
      them. Population-based research is necessary, as empirical findings linking the
      urban environment and mental health have primarily derived from developed
      countries, and may not be generalizable to developing countries. Thus, the
      current study assesses the prevalence of mental health problems (i.e.,
      depression, perceived powerlessness), as well as their community-based predictors
      (i.e., crime, disorder, poverty, poor sanitation, local social capital and
      cohesion), among a sample of 690 residents in three poor urban communities in
      Accra, Ghana. It uncovers that residents in poor urban communities in developing
      countries suffer from mental health problems as a result of local stressors,
      which include not only physical and structural factors but social ones. Social
      capital and social cohesion show complex, often unhealthy, relationships with
      mental health, suggesting considerable drawbacks in making social capital a key
      focus among policymakers. 

PMID- 25754265
TI  - Acupoint herbal patching for allergic rhinitis: a systematic review and meta
      analysis of randomised controlled trials.
AB  - BACKGROUND: Acupoint herbal patching (AHP) is extensively used in treatment of
      allergic rhinitis in China. However, existing systematic review is insufficient.
      OBJECTIVE OF REVIEW: To evaluate the effectiveness and safety of AHP in treating
      allergic rhinitis. SEARCH STRATEGY: We searched seven electronic databases for
      randomised controlled trials (RCTs) from inception until August 2014. EVALUATION
      METHOD: Two authors selected studies, extracted data and evaluated risk of bias
      independently. The Cochrane risk of bias tool was applied to assess the
      methodological quality of the included trials, and RevMan 5.2 software was
      utilised to perform data analysis. RESULTS: Twenty RCTs involving 2438
      participants were included. Most of them were evaluated as high risk of bias.
      Acupoint herbal patching significantly decreased the recurrence rate at 6 months
      compared with Western medicine (RR 0.52; 95% CI 0.42-0.64), and similar effect
      was found for AHP plus Western medicine versus Western medicine (RR 0.53; 95% CI
      0.44-0.65). Acupoint herbal patching appeared to be more effective than placebo
      in improving total clinical symptoms and signs after treatment and at 6 months,
      and in improving quality of life at <3 months and over 3 months. No severe
      adverse effects were found in the AHP groups. CONCLUSIONS: Acupoint herbal
      patching alone or combined with Western medicine appears to be more effective
      than placebo or Western medicine, respectively. Acupoint herbal patching seems to
      be a safe treatment. However, the findings should be interpreted with caution.
      Further large-scale, rigorously designed trials are warranted to confirm the
      findings.

PMID- 25754267
TI  - Erratum to: Neurochemical correlates of accumbal dopamine D2 and amygdaloid 5-HT
      1B receptor densities on observational learning of aggression.

PMID- 25754266
TI  - A new dehydratase conferring innate resistance to thiacetazone and intra-amoebal
      survival of Mycobacterium smegmatis.
AB  - Nontuberculous mycobacteria are innately resistant to most antibiotics, although
      the mechanisms responsible for their drug resistance remain poorly understood.
      They are particularly refractory to thiacetazone (TAC), a second-line
      antitubercular drug. Herein, we identified MSMEG_6754 as essential for the innate
      resistance of Mycobacterium smegmatis to TAC. Transposon-mediated and targeted
      disruption of MSMEG_6754 resulted in hypersusceptibility to TAC. Conversely,
      introduction of MSMEG_6754 into Mycobacterium tuberculosis increased resistance
      100-fold. Resolution of the crystal structure of MSMEG_6754 revealed a homodimer
      in which each monomer comprises two hot-dog domains characteristic of dehydratase
      like proteins and very similar to the HadAB complex involved in mycolic acid
      biosynthesis. Gene inactivation of the essential hadB dehydratase could be
      achieved in M. smegmatis and M. tuberculosis only when the strains carried an
      integrated copy of MSMEG_6754, supporting the idea that MSMEG_6754 and HadB share
      redundant dehydratase activity. Using M. smegmatis-Acanthamoeba co-cultures, we
      found that intra-amoebal growth of the MSMEG_6754 deleted strain was
      significantly reduced compared with the parental strain. This in vivo growth
      defect was fully restored upon complementation with catalytically active
      MSMEG_6754 or HadABC, indicating that MSMEG_6754 plays a critical role in the
      survival of M. smegmatis within the environmental host.

PMID- 25754268
TI  - Doing Research Together: A Study on the Views of Advisors with Intellectual
      Disabilities and Non-Disabled Researchers Collaborating in Research.
AB  - BACKGROUND: Despite an increase in inclusive studies in recent years, research on
      the views of the people with and without disabilities who have participated in
      these studies is scarce. The aim of this study was to explore the perceptions and
      views of advisors with intellectual disabilities and non-disabled researchers who
      collaborated together on a joint project to study transition to adulthood.
      MATERIALS AND METHODS: Two questionnaires were devised, one for advisors and one
      for researchers; two focus groups were held with people with intellectual
      disabilities, three focus groups with researchers, and one focus group with all
      participants together. Thematic analysis was used for the data analysis. RESULTS:
      The advisors valued this experience as an opportunity to learn new skills, freely
      express themselves on matters that affect them, and engage in a socially valued
      activity. The researchers considered that the participation of people with
      intellectual disabilities contributed to improving the quality of the research.
      CONCLUSIONS: The study provides a better understanding of inclusive research
      processes by taking into account participants' views.

PMID- 25754269
TI  - An ethnographic study into the psychological impact and adaptive mechanisms of
      living with hand eczema.
AB  - BACKGROUND: Hand eczema (HE) severely impairs patients' quality of life, and
      causes significant psychological and social distress. There has been little focus
      on how people with HE perceive their disease and how they may be adapting their
      behaviours to cope with their condition. AIM: A survey was carried out to
      investigate how the physical and aesthetic impact of HE may affect patients
      psychologically, and to assess their associated behavioural changes and disease
      perception. METHODS: A 22-item survey covering demographics, disease-related
      questions and psychosocial items was completed by patients with HE via a website.
      RESULTS: In total, 1023 people with HE completed the survey. Of these, 89% stated
      they were embarrassed/self-conscious about their eczema, with 70% of respondents
      reporting wearing gloves or hiding their hands in their pockets. Many respondents
      reported their HE affected their daily activities and choices, with 74% of
      patients reporting that their condition affects the way they handle objects or
      touch people. Regarding relationships, 27% of respondents said physical
      relationships with their partners were affected, and 27% said that
      tension/disagreements between them and their partner or family/friends occurred
      because HE had stopped them doing certain activities. CONCLUSION: HE can have a
      very large psychological impact on sufferers, hugely reducing their self-esteem,
      and as a consequence, having a detrimental effect on their daily activities and
      relationships. The impact of these psychosocial comorbidities has been
      underinvestigated and often underestimated by clinicians, despite being of great
      importance to patients.

PMID- 25754270
TI  - Prenatal exposure to maternal smoking and symptom severity among offspring with
      first-episode nonaffective psychosis.

PMID- 25754271
TI  - Reply: To PMID 25565428.

PMID- 25754272
TI  - Outcome of Patients with Advanced Heart Failure Who Receive Device-Based Therapy
      for Primary Prevention of Sudden Cardiac Death: Insights from the Israeli ICD
      Registry.
AB  - BACKGROUND: Randomized clinical trials have shown conflicting data on the benefit
      of implantable cardioverter defibrillator (ICD) for primary prevention of sudden
      cardiac death in patients with more advanced heart failure (HF) symptoms. Using
      the Israeli ICD Registry data, we sought to examine the effect of HF functional
      class on the outcome of patients who receive device therapy in a real-world
      setting. METHODS: The association between HF functional class (categorized as
      baseline New York Heart Association [NYHA] functional class I and II in [61%] vs
      class III and IV in [39%]) and clinical outcomes was assessed among 913 patients
      who received an ICD (n = 514) or a cardiac resynchronization therapy with a
      defibrillator (CRT-D; n = 399) device and were prospectively followed in the
      Israeli ICD Registry between July 2011 and June 2013. RESULTS: The risk
      associated with advanced HF functional class was significantly different in ICD
      and CRT-D recipients. In the former group, patients with NYHA classes III and IV
      experienced >3-fold increased risk of HF or death (hazard ratio [HR] = 3.28; P <
      0.001), whereas among CRT-D recipients the risk was similar between patients with
      NYHA III/IV and those with less advanced HF symptoms (HR = 0.97 [95% confidence
      interval (CI) 0.54-1.78]; P = 0.42; P value for NYHA functional class by device
      type interaction = 0.002). The risk for ventricular arrhythmia (VA) was
      significantly lower among patients with more advanced NYHA functional class,
      regardless of device type (overall HR = 0.52; 95% CI 0.33-0.91; P = 0.04).
      CONCLUSION: Our findings suggest that patients with less advanced HF symptoms
      experience a greater risk for VA and the development of HF is attenuated in CRT-D
      recipients with more advanced NYHA functional class.

PMID- 25754274
TI  - Epidemiological and etiological characteristics of hand, foot, and mouth disease
      in Wuhan, China from 2012 to 2013: outbreaks of coxsackieviruses A10.
AB  - Hand-foot-mouth disease (HFMD) is a common infectious disease which often occurs
      in young children. It is caused by enteroviruses, most commonly enterovirus71
      (EV71) and Coxsackievirus A16 (CVA16). The present study focuses on the molecular
      epidemiology of the pathogen of HFMD in the Wuhan region of China during the
      period 2012 to 2013. A total of 463 viruses were isolated from throat swab of
      3,208 HFMD patients and analyzed by quantitative RT-PCR with all sets of specific
      primers for EV71, CVA16, and pan-enterovirus. Of the 463 viruses, 111 (21.2%)
      were EV71, 52 (9.6%) were CVA16, and 300 (69.2%) were pan-enterovirus. In pan
      enterovirus isolations 190 (52.8%) were CVA10, 50 (13.9%) were CVA4, 30 were CB2,
      17 were CB3, 13 were CB5 identified by VP4 gene sequencing. Eleven EV71 isolates
      were complete genome sequenced and phylogenetic analysis revealed that the EV71
      strains that circulated in Wuhan belonged to the C4 subgenotype. Among the 190
      CVA10 isolations, 187 CVA10 strains have the same nucleotide sequence, the other
      three CVA10 strains belongs to another type of nucleotide sequence. Phylogenetic
      analysis based on 19 CVA10 isolations suggested that they belonged to the clade
      of Chinese strains, but form different clusters isolated from Japan, Europe. This
      study showed that EVA71 and CVA16 were detected as the predominant viruses (>60%)
      in 2012 and the total reported HFMD cases attained a peak in June and July. In
      contrast, CVA10 was also detected during April 2012 and replaced EVA71 and CVA16
      as the major HFMD-associated pathogen from May 2013.

PMID- 25754273
TI  - The combined serum levels of miR-375 and urokinase plasminogen activator receptor
      are suggested as diagnostic and prognostic biomarkers in prostate cancer.
AB  - This study aimed to assess the applicability of miR-375 in combination with the
      soluble urokinase plasminogen activator receptor (suPAR) protein as a diagnostic
      and/or prognostic biomarker for prostate cancer (PCa) patients. miR-375 levels by
      qRT-PCR and suPAR levels by ELISA were evaluated in serum samples from 146 PCa
      patients, 35 benign prostate hyperplasia (BPH) patients and 18 healthy controls.
      Antigen levels of suPAR differed between healthy controls and PCa or BPH
      patients, whereas miR-375 levels differed between PCa and BPH patients or healthy
      controls (p < 0.001). Additionally, suPAR levels differed between the Gleason sum
      groups GS = 7 versus GS > 7, with higher levels in the latter group (p = 0.011),
      and miR-375 levels were higher in the tumor stage group T3-T4 compared with the
      T1-T2 group (p = 0.039). A high concentration of suPAR was associated with a poor
      disease-specific survival (DSS; p = 0.039). The combination of suPAR and miR-375
      levels identified a patient group possessing high levels for both parameters.
      This was associated with a poorer 10-year overall survival (OS) and DSS, with a
      6.38-fold increased risk of death and a 7.68-fold increased risk of tumor-related
      death (p = 0.00026 and p = 0.014; univariate Cox's regression analysis). In a
      multivariate Cox's regression analysis PCa patients with high levels of suPAR and
      miR-375 showed a 5.72-fold increased risk of death in OS (p = 0.006). In summary,
      the differences between the PCa/BPH/healthy control cohorts for either suPAR and
      miR-375 levels in conjunction with the association of combined high suPAR/miR-375
      levels with a poor prognosis suggest a diagnostic and prognostic impact for PCa
      patients. 

PMID- 25754275
TI  - Ectopic Cushing's syndrome secondary to lung and mediastinal tumours -- report
      from a tertiary care centre in Iran.
AB  - INTRODUCTION: Ectopic Cushing's syndrome (ECS) secondary to neuroendocrine
      tumours (NETs) of the lung and mediastinum are rarely encountered. In this study,
      we present our experience in Iran on 15 patients with ECS secondary to lung and
      mediastinal tumours over a period of 27 years. MATERIAL AND METHODS: Since 1985,
      15 patients with ECS secondary to lung and mediastinal tumours have been
      diagnosed and prospectively followed by the endocrinology team of Taleghani
      Hospital, Tehran, Iran. The clinical signs and symptoms, laboratory findings,
      radiological features, immunohistochemical characteristics, management strategies
      and outcome data are here presented. RESULTS: There were six women and nine men,
      aged 26-70 years, all presenting with typical features of Cushing's syndrome.
      Based on histopathologic evaluations, four patients had small cell lung cancer
      (SCLC) and seven patients had pulmonary NETs, one patient had a thymic NET, and
      one case was diagnosed as a lung tumourlet. The mean +/- SD serum cortisol, 24h
      urine free cortisol and plasma ACTH were 47.2 +/- 20.5 MUg/dL, 2,702 +/- 5,439
      MUg/day, and 220 +/- 147 pg/mL, respectively. Pulmonary lesions ranged in
      diameter from 1.1 to 4 cm (mean 1.9 +/- 1.1 cm). One patient had a 10 cm
      mediastinal mass. The duration of follow up in these cases was between one month
      and seven years (mean 29.9 +/- 27.5 months). The four patients with SCLC died
      within three months of diagnosis. CONCLUSION: Our data demonstrates the protean
      clinical and laboratory manifestations of ECS secondary to lung and mediastinal
      tumours, the problems encountered in diagnosis, and the need for a
      multidisciplinary approach. This study confirms other series from Western Europe
      and North America that, unlike the SCLC patients who show a poor outlook, ECS
      secondary to lung carcinoids has a more favourable prognosis.

PMID- 25754276
TI  - Risk factors of diabetic foot of neuropathic origin in patients with type 2
      diabetes.
AB  - INTRODUCTION: Diabetic foot is a diabetes mellitus complication leading to
      recurrent ulcerations, risk of osteomyelitis and tissue necrosis which may
      finally result in amputation. Diabetic foot of neuropathic origin manifesting as
      autonomic and sensory motor neuropathy is the most common type of this
      complication. The aim of this study was to identify risk factors of diabetic foot
      of neuropathic origin occurrence in patients with type 2 diabetes. MATERIAL AND
      METHODS: The study included 240 patients, 74 with diabetic foot of neuropathic
      origin and 166 with diabetes. Cases and controls were matched in terms of age
      structure. Patients with peripheral arterial disease were excluded from the
      study. The study was conducted in the Gastroenterology and Metabolic Diseases
      Department, Medical University of Warsaw, Poland. We used logistic regression
      models, chi2, U Mann-Whitney's and t-Student tests. RESULTS: Logistic regression
      analysis showed that diabetic foot of neuropathic origin risk factors were: male
      gender (OR = 6.63; 95% CI: 3.31-13.27; p = 0.00001), duration of diabetes (OR =
      1.10; 95% CI: 1.06-1.14; p = 0.00001), height (OR = 1.09; 95% CI: 1.06-1.13; p =
      0.00001), weight (OR = 1.04; 95% CI: 1.04-1.06; p = 0.00001) and waist
      circumference (OR = 1.05; 95% CI: 1.02-1.08; p = 0.001). Although there was a
      correlation between diabetic foot of neuropathic origin and BMI value, it had no
      impact on DF occurrence risk. CONCLUSION: It is possible to identify patients at
      risk of diabetic foot development by evaluating anthropometric features. The
      existence of specific factors increasing the odds of diabetic foot of neuropathic
      origin occurring may lead to the identification of patients at risk of its
      development.

PMID- 25754277
TI  - Atypical phenotypic features among carriers of a novel Q248X nonsense mutation in
      the HNF1B gene.
AB  - INTRODUCTION: Hepatocyte transforming factor 1B-maturity onset diabetes mellitus
      of the young (HNF1B-MODY) is an autosomal dominant type of monogenic diabetes
      caused by a mutation in the gene encoding hepatocyte nuclear factor 1beta (HNF
      1beta). The aim of this study was to determine if a HNF1B gene mutation was
      responsible for a dominantly inherited form of diabetes mellitus among the
      members of a three-generation Polish family. MATERIAL AND METHODS: The index
      subject was a 13-year-old boy with metabolic syndrome, spina bifida occulta,
      posterior urethral valves, congenital ureteropelvic junction obstruction, and a
      family history of diabetes of autosomal dominant trait of inheritance. We
      performed clinical and laboratory examinations of his family and sequenced the
      HNF1B gene. RESULTS: A novel Q248X mutation (nucleotide C to T transition at
      position 742 of the exon 3 of HNF1B gene, resulting in stop codon formation) was
      identified. Phenotypes of family members sharing this mutation are highly
      variable, and include previously known abnormalities of the urinary system and
      pancreas, diabetes mellitus of variable onset and severity, hyperinsulinaemia,
      insulin resistance, metabolic syndrome, elevated aminotransferases,
      hyperbilirubinemia, hyperamylasemia, short stature and cataracts. To the best of
      our knowledge, spina bifida occulta, pectus carinatum, and splenomegaly have not
      been previously reported. CONCLUSIONS: Our results broaden the spectrum of HNF1B
      gene mutations and HNF1B-MODY-related phenotypes.

PMID- 25754278
TI  - Growth hormone/insulin-like growth factor-1 axis, calciotropic hormones and bone
      mineral density in young patients with chronic viral hepatitis.
AB  - INTRODUCTION: Chronic liver disease caused by HBV and HCV infections, due to its
      great prevalence and serious medical consequences, is at the present time a
      significant clinical problem. An impaired liver function can provoke severe
      disturbances in calcium and phosphorus homeostasis, and consequently in the bone
      metabolism resulting in hepatic osteodystrophy. The aim of this study was to
      determine whether there are significant differences in bone mineral density (BMD)
      and/or circadian levels of hormones connected with bone metabolism and bone
      turnover markers in patients with chronic viral hepatitis. MATERIAL AND METHODS:
      Circadian levels (AUC, area under the curve) of GH, IGF-I, IGFBP-3, osteocalcin
      (BGLAP), C-terminal telopeptide of type I collagen (ICTP), PTH, 25(OH)D, total
      calcium and total phosporus were measured in the blood of members of the study
      group (n = 80). BMD was assessed using the dual-energy X-ray absorptiometry
      method of the L2-L4 lumbar spine. Data was compared to that of healthy
      individuals (n = 40). RESULTS: BMD (1.05 g/cm3 vs. 1.20 g/cm3), total calcium
      concentration (2.20 mmol/L vs. 2.45 mmol/L), total phosphorus concentration (1.06
      mmol/L vs. 1.33 mmol/L), IGF-I (AUC 3,982.32 ng/mL vs. 5,167.61 ng/mL), IGFBP-3
      (AUC 725.09 ng/L vs. 944.35 ng/L), 25(OH)D (AUC 356.35 ng/mL vs. 767.53 ng/mL)
      and BGLAP (AUC 161.39 ng/L vs. 298 ng/L) were lower in the study group. GH (AUC
      88.3 ng/mL vs. 48.04 ng/mL), iPTH (AUC 1,201.94 pg/mL vs. 711.73 pg/mL) and ICTP
      (AUC 104.30 MUg/L vs. 54.49 MUg/L) were higher in patients with hepatitis.
      Positive correlations were noted between bone mineral density and IGF-I, IGFBP-3,
      and BGLAP levels. CONCLUSIONS: Chronic viral hepatitis causes a decrease in bone
      mineral density. Impaired liver function disrupts homeostasis of the calcium-
      vitamin D-parathyroid hormone axis and provokes secondary hyperparathyroidism.
      Chronic viral hepatitis induces a decrease in the synthesis of IGF-I and IGFBP-3
      and an increase in GH secretion. Hepatic osteodystrophy is probably caused by
      both changes in calciotropic hormones as well as in the somatotropin hormone
      axis.

PMID- 25754279
TI  - Widespread vitamin D deficiency among adults from northern Poland (54 degrees N)
      after months of low and high natural UVB radiation.
AB  - INTRODUCTION: Widespread vitamin D deficiency has been reported worldwide and
      evidence of its deleterious effects on health has been accumulating. There is
      insufficient data concerning vitamin D status among the Polish adult population.
      The aim of the study was to determine vitamin D status and factors influencing it
      - UVB exposure, supplementation, and diet - among adults in northern Poland
      following months of low and high natural UVB radiation. MATERIAL AND METHODS:
      Adults were recruited in an outpatient clinic. All were examined twice in 2012:
      in winter (in February, March and the first half of April), and autumn (between
      25 September and 8 November). Questionnaire examinations were performed, and
      serum concentrations of 25-hydroxy-vitamin D (25(OH)D), calcium, phosphorus,
      parathyroid hormone (PTH), and alkaline phosphatase (ALP) were determined.
      RESULTS: 40 men and 69 women participated in the study (age 48.4 +/- 15 years,
      body mass index (BMI) 25.9 +/- 4.3 kg/m2, mean +/- SD). Mean 25(OH)D serum level
      in winter was 13.3 +/- 6.6 ng/mL, 81.1% of participants were vitamin D-deficient.
      Mean 25(OH)D concentration in autumn was 22.8 +/- 7.9 ng/mL (42.2% of subjects
      were vitamin D-deficient). Median 25(OH)D and PTH concentrations between the two
      examination periods differed significantly (11.9 vs. 22.1 ng/mL, and 46.3 vs.
      32.2 pg/mL, respectively). In autumn, negative correlations were found between:
      25(OH)D and PTH serum levels, 25(OH)D and BMI values. When compared to respective
      counterparts, participants declaring vitamin D supplementation, and sunbed use
      had significantly higher median 25(OH)D concentrations. CONCLUSIONS: UV exposure
      during the summer was insufficient to provide adequate vitamin D status for
      almost half of the participants by as soon as the early autumn. Our results
      suggest all-year-round vitamin D supplementation should be widely implemented.

PMID- 25754280
TI  - Chronic noise exposure and testosterone deficiency -- meta-analysis and meta
      regression of experimental studies in rodents.
AB  - INTRODUCTION: Chronic psychological distress can cause suppression of the
      hypothalamic-pituitary-testicular axis and thus lead to male hypogonadism, which
      is associated with psycho-social dysfunction, chronic diseases, and as a result,
      considerable economic costs. Conversely, noise is a prototypal environmental
      stressor of growing importance, already linked to birth outcomes and diabetes.
      However, its effects on male testosterone levels have been paid little attention.
      MATERIAL AND METHODS: This paper reports a systematic review and meta-analysis of
      experimental studies in rodents, which have examined the effect of chronic noise
      stress on serum testosterone levels. A systematic search in MEDLINE, EMBASE and
      the Internet yielded seven studies. A quality effects meta-analytical model was
      applied to compute pooled Hedges's g. Quality effects meta-regression was carried
      out as well. RESULTS: We found pooled Hedges's g of -2.41 (95% CI: -3.28, -1.54),
      indicating a very large effect of noise exposure on testosterone. Metaregression
      confirmed that the overall duration of exposure explained a significant
      proportion of the variance across individual effect sizes (Q (1) = 3.95, p =
      0.047). However, there was considerable inter-study heterogeneity (I2 = 82%) and
      publication bias (p = 0.016). After inputting two studies previously thought to
      be missing, the pooled effect dropped to g = -1.53 (95% CI: -3.01, -0.05).
      CONCLUSIONS: Chronic noise exposure of ~ 100 dB leads to a significant reduction
      of serum testosterone in male rodents. Research on humans is highly warranted,
      especially given the steady trend in Western societies for increasing the burden
      of both male hypogonadism and noise pollution.

PMID- 25754281
TI  - Emotional functions in transsexuals after the first step in physical
      transformation.
AB  - Transsexuals have to face multiple medical, social and bureaucratic problems.
      These problems are not only encountered before the transformation, but also
      during and after medical procedures. In the search for improvement of transsexual
      individuals' quality of life during therapy, it seems desirable to supplement
      hormonal treatments with psychological explorations. This study was conducted
      with the aim of defining emotional conditions and included 28 transsexual female
      to-male (F/M) patients and two gender-divided control groups (males and females)
      of similar age. The following psychometric scales were used: CECS (Courtauld
      Emotional Control Scale constructed by M. Watson and S. Greer in the Polish
      Adaptation by Z. Juczynski), ISCL (the Polish Adaptation of the State-Trait
      Anxiety Inventory for Adults by T. Sosnowski), and GSES (the Polish Adaptation of
      the R. Schwarzer, M. Jerusalem Generalized Self-Efficacy Scaleby Z. Juczynski and
      K. Wrzesniewski). Transsexual F/M patients appeared very similar to males in the
      male control group in terms of their subjective selfefficacy and state-trait
      anxiety, while their subjective belief of anxiety and fear control was more
      comparable to that of the female controls. It was also found to be statistically
      significantly lower than in the male controls. 

PMID- 25754282
TI  - Comparison of chromogranin A (CgA) levels in serum and plasma (EDTA2K) and the
      respective reference ranges in healthy males.
AB  - INTRODUCTION: Chromogranin A (CgA) is a major, nonspecific marker of
      neuroendocrine tumours (NET). There are a few routinely used assays for the
      measurement of CgA concentration in serum or plasma. These assays differ in
      analytical techniques (radioimmunoassay, ELISA, CLIA, TRACE), have different
      calibrators, and use different antibodies which recognise different epitopes of
      CgA molecule. Our study was designed to confirm the noted earlier differences in
      CgA levels measured in serum and plasma, and to establish respective reference
      ranges in a group of healthy males. MATERIAL AND METHODS: In 145 male blood
      donors (age 19-61 years, mean = 35.7), blood was collected into two tubes: one
      with EDTA2K (plasma) and one with clot activator (serum). Chromogranin A was
      measured by immunoradiometric kit (CIS bio, France). RESULTS: In blood donors,
      the median (and the range) of CgA concentration were as follows for serum samples
      - 42.0 ng/mL (16-108 ng/mL) and for plasma (EDTA2K) samples - 58.0 ng/mL (23-153
      ng/mL). The differences between serum and plasma ranged 15-75% (median 26%).
      Plasma CgA levels were significantly higher in relation to serum CgA levels (p <
      0.0001). Correlation of CgA in serum and plasma was r = 0.8493; p < 0.01. The
      reference ranges for CgA measured in serum and plasma in males, expressed as 2.5
      to 97.5 percentiles, were: 21.0-108.0 ng/mL and 31.0-153.0 ng/mL respectively.
      CONCLUSIONS: 1. Significant differences in the concentrations of CgA measured in
      plasma and in serum demand the application of separate reference ranges adjusted
      to the type of investigated material. 2. Each laboratory should recommend only
      one sort of sample material for CgA assay.

PMID- 25754283
TI  - Aortopathies in Turner syndrome -- new strategies for evaluation and treatment.
AB  - Turner syndrome is a rare genetic disorder which impairs women's growth,
      reproductive function, cardiovascular development and other functions. This
      syndrome has been proposed as an independent risk marker for cardiovascular
      disease. Despite this, life-threatening cardiovascular outcomes affecting young
      women are dismissed because of incomplete follow up. During assessment due to
      their smaller stature, it should be noted that, although the ascending aorta
      diameter is normal in absolute terms, after indexation for body size, patients
      with Turner syndrome may have a dilated aorta.Based on recent guidelines and the
      latest studies, there is new evidence on the use of magnetic resonance imaging in
      diagnosing aortic lesions. New management possibilities of aortopathies have also
      been discussed. This approach should optimise medical care for women with Turner
      syndrome, but many areas of uncertainty still remain in the diagnosis and
      management of this syndrome, and new prospective studies are needed. 

PMID- 25754284
TI  - Unilateral laparoscopic adrenalectomy following partial transsphenoidal
      adenomectomy of pituitary macroadenoma - life-saving procedure in a patient with
      ACTH-dependent Cushing's syndrome.
AB  - INTRODUCTION: Cushing's disease is the most common cause of endogenous
      hypercortisolemia, in 90% of cases due to microadenoma. Macroadenoma can lead to
      atypical hormonal test results and complete removal of the tumour is unlikely.
      CASE REPORT: A 77-year-old woman with diabetes and hypertension was admitted
      because of fatigue, proximal muscles weakness, lower extremities oedema, and
      worsening of glycaemic and hypertension control. Physical examination revealed
      central obesity, 'moon'-like face, supraclavicular pads, proximal muscle atrophy,
      and skin hyperpigmentation. Biochemical and hormonal results were as follows: K
      2.3 mmol/L (3.6-5), cortisol 8.00 86 MUg/dL (6.2-19.4) 23.00 76 MUg/dL, ACTH 8.00
      194 pg/mL (7.2-63.3) 23.00 200 pg/mL, DHEAS 330 MUg/dL (12-154). CRH stimulation
      test showed lack of ACTH stimulation > 35%, overnight high dose DST revealed no
      suppression of cortisol. Chest and abdominal CT as well as somatostatin receptor
      scan didn't show ectopic tumour responsible for ACTH oversecretion. MRI revealed
      a pituitary macroadenoma (28 * 20 * 17 mm) extending towards the left cavernous
      sinus. After partial transsphenoidal adenomectomy, serum cortisol of 40 MUg/dL
      was obtained. The patient's condition was still very poor, so unilateral
      adrenalectomy was performed. After surgery, serum morning cortisol level dropped
      to 20 MUg/dL and the patient's condition improved significantly. 26 months after
      the operations, the patient remains in remission. Because her life expectancy
      exceeds the prognosed duration of remission with the presence of pituitary tumour
      remnants and intact left adrenal gland, the patient was qualified to radiosurgery
      with a Gamma Knife. CONCLUSION: In selected cases, unilateral, laparascopic
      adrenalectomy may serve as a life-saving procedure in a patient with
      ACTHdependent Cushing's syndrome.

PMID- 25754285
TI  - Flow cytometry in the differential diagnostics of Hashimoto's thyroiditis and
      MALT lymphoma of the thyroid.
AB  - INTRODUCTION: A combination of traditional cytology methods with fluorescence
      activated cell sorting (FACS) analysis of fine-needle aspiration biopsy (FNAB)
      material is considered a powerful diagnostic tool in the differential diagnosis
      of thyroid lesions suspected of mucosa-associated lymphoid tissue lymphoma (MALT
      L). The aim of this study was to demonstrate the FACS-based diagnostic process of
      thyroid lesions in a clinical situation where ultrasound and cytological
      examinations did not allow differentiation between Hashimoto's thyroiditis (HT)
      and MALT-L. MATERIAL AND METHODS: The patients analysed in this study presented
      significantly different clinical courses of thyroid disease: quickly enlarging
      painless tumour of the thyroid right lobe in the first case, and chronic HT with
      palpable tumour in the thyroid isthmus in the second patient. Due to the
      suspicion of MALT-L resulting from indeterminate ultrasound and FNAB-cytology
      results, FNAB material was obtained from all the previously examined thyroid
      lesions and directly subjected to FACS assessment, encompassing kappa/lambda
      light chain restriction analysis, as well as measurements of B and T cell surface
      antigens. RESULTS: The FACS analysis of FNAB material obtained from our patients
      did not show any definite signs of light chain restriction. Although one of the
      samples showed a borderline value of kappa/lambda ratio (kappa/lambda = 0.31),
      further immunophenotyping confirmed clonal expansion in none of the examined
      thyroid regions. Histopathological findings documented the diagnosis of HT in
      both clinical cases. CONCLUSION: We believe that FACS represents a useful and
      reliable complementary diagnostic measure in FNAB-based differential diagnosis of
      lymphoproliferative thyroid disorders.

PMID- 25754286
TI  - Adrenal-preserving surgery of adrenal tumours.
AB  - Currently, laparoscopic adrenalectomy is seen as more than just the preferred
      method, in fact as a routine procedure, always bearing in mind, however, the
      developed restraints on its usage. The size of the tumour, recurrent disease, and
      the existing invasive process all remain factors which determine the indications
      for operation. The situation is similar in cases of qualifying for sparing (non
      radical) operations on adrenal glands. The basic challenge in terms of
      qualification, choice of technique and the range of operation of adrenal lesions
      remains: obtaining a reliable preoperative diagnosis, the localisation of lesions
      including their ectopic location, the evaluation of the imaging phenotype, as
      well as a proper pre-surgical preparation. Maintaining one third of properly
      vascularised adrenal mass allows one to avoid a substitutive therapy, with the
      possible necessity of its application in stressful situations. The first partial
      adrenalectomy has been conducted on a patient with a bilateral pheochromocytoma,
      in order to retain the glucocorticoid adrenal functions. The recommendations for
      its administration remain: hereditary pheochromocytoma of at least 2cm diameter,
      unilateral adenoma of at least 5cm diameter in Cushing's syndrome without any
      concomitant lesions in the oposite adrenal gland, and unilateral adenoma in
      Conn's syndrome. It seems that non-radical resection should always be considered
      for patients at risk of bilateral adrenalectomy in cases of concomitant lesions
      in both adrenals. 

PMID- 25754287
TI  - The vascularized periosteum flap as novel tissue engineering model for repair of
      cartilage defects.
AB  - Periosteum is a promising tissue engineering scaffold in research of cartilage
      repair; so far however, periosteum transfers have not been realized successfully
      because of insufficient nourishment of the graft. In a translational approach we,
      for the first time, designed a vascularized periosteum flap as 'independent'
      biomaterial with its own blood supply to address this problem and to reconstruct
      circumscript cartilage defects. In six 3-month-old New Zealand rabbits, a
      critical size cartilage defect of the medial femur condyle was created and
      covered by a vascularized periosteum flap pedicled on the saphenous vessels.
      After 28 days, formation of newly built cartilage was assessed macroscopically,
      histologically and qualitatively via biomechanical compression testing, as well
      as on molecular biological level via immunohistochemistry. All wounds healed
      completely, all joints were stable and had full range of motion. All flaps
      survived and were perfused through their pulsating pedicles. They showed a stable
      attachment to the bone, although partially incomplete adherence. Hyaline
      cartilage with typical columnar cell distribution and positive Collagen II
      staining was formed in the transferred flaps. Biomechanical testing revealed a
      significantly higher maximum load than the positive control, but a low
      elasticity. This study proved that vascularization of the periosteum flap is the
      essential step for flap survival and enables the flap to transform into
      cartilage. Reconstruction of circumscript cartilage defects seems to be possible.
      Although these are the first results out of a pilot project, this technique, we
      believe, can have a wide range of potential applications and high relevance in
      the clinical field. 

PMID- 25754288
TI  - Separation of cellular and BOLD contributions to T2* signal relaxation.
AB  - PURPOSE: The development of a reliable clinical technique for quantitative
      measurements of the parameters defining the BOLD effect, i.e., oxygen extraction
      fraction (OEF), and deoxygenated cerebral blood volume, dCBV, is needed to study
      brain function in health and disease. Herein we propose such a technique that is
      based on a widely available gradient recalled echo (GRE) MRI. THEORY AND METHODS:
      Our method is based on GRE with multiple echoes and a model of signal decay
      (Yablonskiy, MRM 1998) that takes into account microscopic cellular (R2),
      mesoscopic (BOLD), and macroscopic (background field gradients) contributions to
      the GRE signal decay with additional accounting for physiologic fluctuations.
      RESULTS: Using 3 Tesla MRI, we generate high resolution quantitative maps of R2*,
      R2, R2', and tissue concentration of deoxyhemoglobin, the latter providing a
      quantitative version of SWI. Our results for OEF and dCBV in gray matter are in a
      reasonable agreement with the literature data. CONCLUSION: The proposed approach
      allows generating high resolution maps of hemodynamic parameters using clinical
      MRI. The technique can be applied to study such tissues as gray matter, tumors,
      etc.; however, it requires further development for use in tissues where extra-
      and intracellular compartments possess substantially different frequencies and
      relaxation properties (e.g., white matter).

PMID- 25754289
TI  - A lifetime approach to major depressive disorder: The contributions of
      psychological interventions in preventing relapse and recurrence.
AB  - Major depressive disorder (MDD) is highly disabling and typically runs a
      recurrent course. Knowledge about prevention of relapse and recurrence is crucial
      to the long-term welfare of people who suffer from this disorder. This article
      provides an overview of the current evidence for the prevention of relapse and
      recurrence using psychological interventions. We first describe a conceptual
      framework to preventive interventions based on: acute treatment; continuation
      treatment, or; prevention strategies for patients in remission. In brief,
      cognitive-behavioral interventions, delivered during the acute phase, appear to
      have an enduring effect that protects patients against relapse and perhaps others
      from recurrence following treatment termination. Similarly, continuation
      treatment with either cognitive therapy or perhaps interpersonal psychotherapy
      appears to reduce risk for relapse and maintenance treatment appears to reduce
      risk for recurrence. Preventive relapse strategies like preventive cognitive
      therapy or mindfulness based cognitive therapy (MBCT) applied to patients in
      remission protects against subsequent relapse and perhaps recurrence. There is
      some preliminary evidence of specific mediation via changing the content or the
      process of cognition. Continuation CT and preventive interventions started after
      remission (CBT, MBCT) seem to have the largest differential effects for
      individuals that need them the most. Those who have the greatest risk for relapse
      and recurrence including patients with unstable remission, more previous
      episodes, potentially childhood trauma, early age of onset. These prescriptive
      indications, if confirmed in future research, may point the way to personalizing
      prevention strategies. Doing so, may maximize the efficiency with which they are
      applied and have the potential to target the mechanisms that appear to underlie
      these effects. This may help make this prevention strategies more efficacious. 

PMID- 25754290
TI  - Persistent aggregates in apheresis platelet concentrates.
AB  - BACKGROUND: Aggregates often appear during apheresis. Sometimes, these persist
      throughout storage, causing product wastage. This study assessed product quality
      of apheresis concentrates containing persistent aggregates (PA) and aimed to
      identify the factors that contribute to their formation. METHODS: Donation (n =
      180) and platelet indices (n >= 10) from apheresis concentrates with PA were
      compared with aggregate-free products. RESULTS: The proportion of donors with at
      least one previous PA donation was twofold higher in the PA group (P < 0.0001)
      indicating a donor dependence. Significantly higher donor whole blood platelet
      counts (286 +/- 50 vs. 266 +/- 49 * 10(3) /MUl, P < 0.0001) and higher apheresis
      yields (6.0 +/- 1.6 vs. 5.4 +/- 1.5 * 10(11) , P < 0.0001) were noted in the PA
      group. Haematocrit was also slightly higher, but age, gender and body mass were
      similar. The pH of PA products on day six postdonation was significantly lower (P
      < 0.001), in line with higher lactic acid concentrations. Flow cytometry showed
      no differences in GPIbalpha levels or phosphatidylserine exposure. However, there
      was slightly more integrin activation as well as increased degranulation measured
      by P-selectin expression. Cytokine concentrations were also significantly higher
      in PA concentrates. Aggregation was normal in response to SFLLRN peptide and
      collagen stimulation, but agglutination at low-dose ristocetin was significantly
      higher (P = 0.01) in PA products. Finally, PA were disintegrated by plasmin
      mediated thrombolysis but not by integrin alphaIIb beta3 inhibition. CONCLUSION:
      Products with PA have acceptable quality parameters, but additional functional
      studies are warranted. Furthermore, PA are more likely to recur in certain donors
      who have higher platelet counts.

PMID- 25754291
TI  - Development of an ultrasensitive immunochromatographic assay (ICA) strip for the
      rapid detection of phenylethanolamine A in urine and pork samples.
AB  - In this study a one-step immunochromatographic assay based on competitive format
      was developed for the rapid detection of phenylethanolamine A (PEAA) residues in
      urine and pork samples. A monoclonal antibody against PEAA was produced from
      BALB/c mice immunized with the PEAA-BSA conjugate. The results of this
      qualitative test strip were to be interpreted visually. The visual detection
      limit (VDL) and threshold level of the optimized immunochromatographic assay for
      PEAA were 0.1 ng/mL and 0.5 ng/mL, respectively. Cross-reactions with other beta
      agonists were not significant inhibitions to the performance of the test strip
      assay. The results from the test strip were in a good agreement with those
      obtained using a high performance liquid chromatography-tandem mass spectrometry
      (HPLC-MS/MS) assay. The immunochromatographic assay developed here was a useful
      on-site screening tool that is rapid to use, low in cost, and extremely
      convenient for the detection of PEAA in urine samples and pork samples. 

PMID- 25754293
TI  - Small molecules with big impact: terpenoid phytoalexins as key factors in maize
      stress tolerance.

PMID- 25754292
TI  - The Spemann organizer meets the anterior-most neuroectoderm at the equator of
      early gastrulae in amphibian species.
AB  - The dorsal blastopore lip (known as the Spemann organizer) is important for
      making the body plan in amphibian gastrulation. The organizer is believed to
      involute inward and migrate animally to make physical contact with the
      prospective head neuroectoderm at the blastocoel roof of mid- to late-gastrula.
      However, we found that this physical contact was already established at the
      equatorial region of very early gastrula in a wide variety of amphibian species.
      Here we propose a unified model of amphibian gastrulation movement. In the model,
      the organizer is present at the blastocoel roof of blastulae, moves vegetally to
      locate at the region that lies from the blastocoel floor to the dorsal lip at the
      onset of gastrulation. The organizer located at the blastocoel floor contributes
      to the anterior axial mesoderm including the prechordal plate, and the organizer
      at the dorsal lip ends up as the posterior axial mesoderm. During the early step
      of gastrulation, the anterior organizer moves to establish the physical contact
      with the prospective neuroectoderm through the "subduction and zippering"
      movements. Subduction makes a trench between the anterior organizer and the
      prospective neuroectoderm, and the tissues face each other via the trench.
      Zippering movement, with forming Brachet's cleft, gradually closes the gap to
      establish the contact between them. The contact is completed at the equator of
      early gastrulae and it continues throughout the gastrulation. After the contact
      is established, the dorsal axis is formed posteriorly, but not anteriorly. The
      model also implies the possibility of constructing a common model of gastrulation
      among chordate species. 

PMID- 25754294
TI  - Proton beam therapy for pediatric ependymoma.
AB  - BACKGROUND: The aim of this study was to evaluate the efficacy of proton beam
      therapy for pediatric patients with ependymoma. METHODS: Proton beam therapy was
      conducted for six patients (three boys and three girls; age, 2-6 years; median, 5
      years) with ependymoma. The tumors were WHO grades 2 and 3 in two and four
      patients, respectively. All patients underwent surgery (subtotal and gross total
      resection in three patients each) and proton beam therapy at doses of 50.4-61.2
      GyE (median, 56.7 GyE). The mean doses to normal brain tissue in proton beam
      therapy and photon radiotherapy were simulated using the same treatment planning
      computed tomography images. RESULTS: All patients completed the planned
      irradiation. The follow-up period was 13-44 months (median, 24.5 months) from
      completion of proton beam therapy and all patients were alive at the end of this
      period. Local recurrence in the treatment field occurred in one patient at 4
      months after proton beam therapy at 50.4 GyE. Alopecia and mild dermatitis
      occurred in all patients, but there was no severe toxicity. One patient had a
      once-off seizure after proton beam therapy and alopecia persisted in another
      patient for 31 months, but no patients had difficulty with daily life. The
      simulation showed that proton beam therapy reduces the dose to normal brain
      tissue by approximately half compared with photon radiotherapy. CONCLUSIONS:
      Proton beam therapy for pediatric ependymoma is safe, does not have specific
      toxicities, and can reduce irradiation of normal brain tissue.

PMID- 25754295
TI  - Creativity and innovation in nutrition education.

PMID- 25754296
TI  - Is impact a factor?

PMID- 25754297
TI  - Patterns of energy drink advertising over US television networks.
AB  - OBJECTIVE: To describe programming themes and the inclusion of adolescents in the
      base audience for television channels with high levels of energy drink
      advertising airtime. DESIGN: Secondary analysis of energy drink advertising
      airtime over US network and cable television channels (n = 139) from March, 2012
      to February, 2013. Programming themes and the inclusion of adolescents in each
      channel's base audience were extracted from cable television trade reports. MAIN
      OUTCOME MEASURE: Energy drink advertising airtime. ANALYSIS: Channels were ranked
      by airtime; programming themes and the inclusion of adolescents in the base
      audience were summarized for the 10 channels with the most airtime. RESULTS: Over
      the study year, 36,501 minutes (608 hours) were devoted to energy drink
      advertisements; the top 10 channels accounted for 46.5% of such airtime.
      Programming themes for the top 10 channels were music (n = 3), sports (n = 3),
      action-adventure lifestyle (n = 2), African American lifestyle (n = 1), and
      comedy (n = 1). MTV2 ranked first in airtime devoted to energy drink
      advertisements. Six of the 10 channels with the most airtime included adolescents
      aged 12-17 years in their base audience. CONCLUSIONS AND IMPLICATIONS: Energy
      drink manufacturers primarily advertise on channels that likely appeal to
      adolescents. Nutritionists may wish to consider energy drink media literacy when
      advising adolescents about energy drink consumption.

PMID- 25754298
TI  - Farmers' markets and the local food environment: identifying perceived
      accessibility barriers for SNAP consumers receiving temporary assistance for
      needy families (TANF) in an urban Oklahoma community.
AB  - OBJECTIVE: To examine barriers to farmers' market (FM) use by Supplemental
      Nutrition Assistance Program (SNAP) consumers receiving Temporary Assistance for
      Needy Families. DESIGN: Focus groups. SETTING: An urban community in Oklahoma.
      PARTICIPANTS: Supplemental Nutrition Assistance Program beneficiaries receiving
      Temporary Assistance for Needy Families (n = 64 across 8 focus groups).
      PHENOMENON OF INTEREST: Perceptions about FM foods and barriers to FM use.
      ANALYSIS: Transcript-based content analysis using the 5 dimensions of access
      framework. RESULTS: Few participants ate fresh produce regularly and most
      appreciated the convenience of shopping at a supermarket. Farmers' markets were
      not perceived as available or accommodating to shopping needs and affordability
      and acceptability concerns were expressed. Few were aware of FMs that accepted
      SNAP. Emerging themes suggested residential segregation and cultural barriers to
      FM use. CONCLUSIONS AND IMPLICATIONS: Farmers' market managers, community
      nutritionists, and researchers should develop interventions that correct common
      misperceptions about FM products, minimize access barriers, and increase
      awareness of SNAP payment options. Residential segregation and cultural barriers
      may have a role in FM use and should be explored further.

PMID- 25754299
TI  - Impact of non-diet approaches on attitudes, behaviors, and health outcomes: a
      systematic review.
AB  - OBJECTIVE: To determine the overall effect of non-diet, weight-neutral
      interventions on factors such as weight, biochemical measures, food and activity
      behavior, body image, and mental health. DESIGN: Systematic review of
      intervention literature. SETTING: Group classes in community and worksite
      settings (14 studies), and individual counseling (1) and online education (1) in
      college settings. PARTICIPANTS: Eighteen research articles (representing 16
      studies) evaluating non-diet interventions using quasi-experimental and
      randomized study designs with either a comparison or control group. MAIN OUTCOME
      MEASURES: Anthropometric, physiological, psychological, and dietary intake.
      ANALYSIS: Systematic search of 168 articles and review of 18 articles meeting
      inclusionary criteria. RESULTS: Non-diet interventions resulted in statistically
      significant improvements in disordered eating patterns, self-esteem, and
      depression. None of the interventions resulted in significant weight gain or
      worsening of blood pressure, blood glucose, or cholesterol, and in 2 studies
      biochemical measures improved significantly compared with the control or diet
      group. Primary limitations were inconsistent definitions of non-diet approaches
      and the use of different assessment instruments for measuring outcomes.
      CONCLUSIONS AND IMPLICATIONS: Because of the long-term ineffectiveness of weight
      focused interventions, the psychological improvements seen in weight-neutral, non
      diet interventions warrant further investigation.

PMID- 25754300
TI  - Testing the effectiveness of in-home behavioral economics strategies to increase
      vegetable intake, liking, and variety among children residing in households that
      receive food assistance.
AB  - OBJECTIVE: To test the effectiveness of behavioral economics strategies for
      increasing vegetable intake, variety, and liking among children residing in homes
      receiving food assistance. DESIGN: A randomized controlled trial with data
      collected at baseline, once weekly for 6 weeks, and at study conclusion. SETTING:
      Family homes. PARTICIPANTS: Families with a child (9-12 years) will be recruited
      through community organizations and randomly assigned to an intervention (n = 36)
      or control (n = 10) group. INTERVENTION: The intervention group will incorporate
      a new behavioral economics strategy during home dinner meal occasions each week
      for 6 weeks. Strategies are simple and low-cost. MAIN OUTCOME MEASURE(S): The
      primary dependent variable will be child's dinner meal vegetable consumption
      based on weekly reports by caregivers. Fixed independent variables will include
      the strategy and week of strategy implementation. Secondary dependent variables
      will include vegetable liking and variety of vegetables consumed based on data
      collected at baseline and study conclusion. ANALYSIS: Mean vegetable intake for
      each strategy across families will be compared using a mixed-model analysis of
      variance with a random effect for child. In additionally, overall mean changes in
      vegetable consumption, variety, and liking will be compared between intervention
      and control groups.

PMID- 25754301
TI  - Abdominal obesity perception in Turkish population.

PMID- 25754302
TI  - Radiation dose reduction for coronary artery calcium scoring at 320-detector CT
      with adaptive iterative dose reduction 3D.
AB  - To assess the possibility of reducing the radiation dose for coronary artery
      calcium (CAC) scoring by using adaptive iterative dose reduction 3D (AIDR 3D) on
      a 320-detector CT scanner. Fifty-four patients underwent routine- and low-dose CT
      for CAC scoring. Low-dose CT was performed at one-third of the tube current used
      for routine-dose CT. Routine-dose CT was reconstructed with filtered back
      projection (FBP) and low-dose CT was reconstructed with AIDR 3D. We compared the
      calculated Agatston-, volume-, and mass scores of these images. The overall
      percentage difference in the Agatston-, volume-, and mass scores between routine-
      and low-dose CT studies was 15.9, 11.6, and 12.6%, respectively. There were no
      significant differences in the routine- and low-dose CT studies irrespective of
      the scoring algorithms applied. The CAC measurements of both imaging modalities
      were highly correlated with respect to the Agatston- (r = 0.996), volume- (r =
      0.996), and mass score (r = 0.997; p < 0.001, all); the Bland-Altman limits of
      agreement scores were -37.4 to 51.4, -31.2 to 36.4 and -30.3 to 40.9%,
      respectively, suggesting that AIDR 3D was a good alternative for FBP. The mean
      effective radiation dose for routine- and low-dose CT was 2.2 and 0.7 mSv,
      respectively. The use of AIDR 3D made it possible to reduce the radiation dose by
      67% for CAC scoring without impairing the quantification of coronary
      calcification.

PMID- 25754305
TI  - Extending the MODPATH Algorithm to Rectangular Unstructured Grids.
AB  - The recent release of MODFLOW-USG, which allows model grids to have irregular,
      unstructured connections, requires a modification of the particle-tracking
      algorithm used by MODPATH. This paper describes a modification of the semi
      analytical particle-tracking algorithm used by MODPATH that allows it to be
      extended to rectangular-based unstructured grids by dividing grid cells with
      multi-cell face connections into sub-cells. The new method will be incorporated
      in the next version of MODPATH which is currently under development. 

PMID- 25754304
TI  - Giant neglected squamous cell carcinoma of the skin.
AB  - Nonmelanoma skin cancers (NMSCs) are the most common type of skin tumor,
      representing about one-third of all malignancies diagnosed worldwide each year.
      Cutaneous squamous cell carcinoma (cSCC) is the second most common form of NMSCs
      and the risk of cSCC invasiveness should be assessed on the basis of tumor size,
      anatomical location, and histological subtype. Although most cSCCs are early
      diagnosed and successfully treated, in a small percentage of patients with giant
      cSCC (maximum diameter >5 cm), metastases may occur; treatment options are
      limited and not really effective. We report the case of a giant metastatic cSCC
      that had been neglected for more than 20 years. Radiotherapy or surgery were not
      feasible and polichemotherapy (cisplatin, 5-fluorouracil and paclitaxel) was not
      effective. Therefore, the patient was treated with palliative electrochemotherapy
      (ECT) achieving a partial reduction of cutaneous metastasis and pain relief but
      unfortunately the patient died 3 months after the second ECT treatment. 

PMID- 25754303
TI  - Heparanase released from mesenchymal stem cells activates integrin beta1/HIF
      2alpha/Flk-1 signaling and promotes endothelial cell migration and angiogenesis.
AB  - Heparanase plays important roles in tumor angiogenesis. Our previous study
      demonstrated that hypoxic preconditioning (HPC) enhanced the angiogenic and
      therapeutic effects of mesenchymal stem cells (MSCs), effects that were
      paralleled by enhanced heparanase expression. This study was designed to
      elucidate the role of heparanase in the improved therapeutic properties of HPC
      MSCs and to explore underlying mechanisms using an ischemic rat hind limb model.
      MSCs transfected with heparanase (MSC(hpa) ) or empty vector (MSC(null) ) were
      delivered by intramuscular injections to ischemic hind limbs. Hind limbs that
      received MSC(hpa) recovered blood flow more rapidly at 7 days and acquired higher
      capillary density at 14 days compared with MSC(null) . Conditioned medium from
      MSC(hpa) increased endothelial cell migration and promoted greater tube formation
      relative to that from the MSC(null) groups. Vascular endothelial growth factor
      receptor 2 (VEGFR2, Flk-1) and its downstream signaling pathway (p38MAPK/HSP27)
      were significantly increased in human umbilical vein endothelial cells (HUVECs)
      after treatment with MSC(hpa) conditioned medium. Each of these responses was
      decreased by cocultured with MSC(hpa-KD) conditioned medium. MSC(hpa) conditioned
      medium activated hypoxia-inducible factor-2alpha (HIF-2alpha) and increased in
      parallel the transcript level of Flk-1 as determined by chromatin
      immunoprecipitation-PCR and luciferase assays. Analyses of integrin expression
      revealed an important role for integrin beta1 in the regulation of HIF-2alpha.
      All angiogenic effects of MSC(hpa) conditioned medium were abolished by knockdown
      of integrin beta1, HIF-2alpha, and Flk-1 in HUVECs with selective shRNAs. These
      findings identify heparanse as a key regulator of angiogenesis by MSCs. We
      propose a novel pathway wherein heparanse sequentially activates integrin beta1,
      HIF-2alpha, Flk-1, and p38MAPK/HSP27 with corresponding enhancement of
      angiogenesis.

PMID- 25754306
TI  - The entourage effect of the phytocannabinoids.

PMID- 25754307
TI  - The interaction between maternal and post-hatch n-3 fatty acid supplementation in
      broiler diets.
AB  - This study investigated whether offspring from n-3-supplemented breeders have an
      enhanced performance and immune organ weight when fed a post-hatch n-3-enriched
      diet in comparison with their control-fed counterparts and the importance of
      timing of omega-3 supplementation. Therefore, 480 Ross-308 broiler breeder hens
      were fed one of four different diets (120/treatment). The control diet (CON) was
      a basal diet, rich in n-6 fatty acids (FA). The three other diets were enriched
      in n-3 FA, formulated to obtain a different EPA/DHA ratio of 1/1 (EPA = DHA), 1/2
      (DHA) or 2/1 (EPA). At 33 weeks of age, eggs were incubated to obtain 1440
      offspring. They were set up according to their maternal diet and sex in 48 pens
      of 30 chicks each (12 pens per maternal treatment: six male and six female). Half
      of the offspring were given a post-hatch control diet, whereas to other half
      received an n-3-supplemented diet. Zootechnical performance was followed for
      starter, grower and finisher phase, and at the end of each phase two, chicks per
      pen were sacrificed to determine the weight of the immune organs. No interaction
      was found between maternal and post-hatch n-3 treatment for zootechnical
      performance. An interaction arose between the maternal and post-hatch n-3
      supplementation for proportional bursa weight at day 1 and day 14 and
      proportional liver weight at day 14, but effects on immune organ weight were
      rather limited. Offspring post-hatch n-3 supplementation did not enhance maternal
      n-3 supplementation. 

PMID- 25754308
TI  - Parental transmission of risk for cannabis use disorders to offspring.
AB  - AIMS: We investigated the risk of cannabis use disorder (CUD) among probands as a
      function of parental psychopathology and explored parent-offspring gender
      concordance as a mechanism of parental CUD transmission to offspring. DESIGN:
      Four waves of data collection from a longitudinal epidemiological study of
      psychopathology among a regionally representative sample. SETTING: Participants
      were selected randomly from western Oregon, USA, and were initially assessed
      during mid-adolescence. PARTICIPANTS: The reference sample included 719 probands
      and their biological mothers and fathers. MEASUREMENTS: CUD episodes among
      probands were assessed with semistructured diagnostic interviews between mid
      adolescence and young adulthood. Life-time psychiatric disorders among parents of
      probands were assessed when probands were approximately 24 years of age.
      FINDINGS: There was an increased risk for CUD onset among probands with parental
      histories of CUD [hazard ratio (HR) = 1.93, 95% confidence interval (CI) = 1.30
      2.88], hard drug use disorders (HR = 1.96, 95% CI = 1.32-2.90) or antisocial
      personality disorder (HR = 1.73, 95% CI = 1.06-2.82). A significant parent
      offspring gender concordance effect indicated that females with a maternal CUD
      history were at higher risk for CUD onset compared with females without a
      maternal CUD (HR = 3.10, 95% CI = 1.52-6.34). Maternal CUD was not associated
      with CUD onset among males (P = 0.570), nor was there evidence for parent
      offspring gender concordance effects for paternal CUD-specific transmission (P =
      0.114). CONCLUSIONS: Parental histories of antisocial personality and illicit
      substance use disorders are associated with increased risk for cannabis use
      disorder onset in offspring, especially among females with maternal cannabis use
      disorder histories.

PMID- 25754309
TI  - Volatile composition and sensory properties of Vanilla * tahitensis bring new
      insights for vanilla quality control.
AB  - BACKGROUND: Vanilla * tahitensis produced in French Polynesia has a unique
      flavour among vanilla species. However, data on volatiles and sensory properties
      remain limited. In this study, the volatile composition and sensory properties of
      V. * tahitensis from three Polynesian cultivars and two origins (French
      Polynesia/Papua New Guinea) were determined by gas chromatography-mass
      spectrometry and quantitative descriptive analysis, respectively, and compared to
      Vanilla planifolia. RESULTS: Vanilla species, origins and cultivars were
      differentiated by their volatile and sensory profiles using principal component
      analysis. The V. * tahitensis flavour from French Polynesia was characterized by
      a well-balanced sensory profile, having strong anise and caramel notes due to
      high levels of anisyl compounds. V. * tahitensis from Papua New Guinea was
      distinct from that of French Polynesia, having strong spicy, fruity, brown rum
      notes due to p-vinylguaiacol, p-cresol and esters. Vanilla planifolia showed
      stronger phenolic, woody, smoky notes due to guaiacol, creosol and phenol, which
      were found to be biomarkers of the species. Vanilla sensory properties were
      linked by partial least squares regression to key volatile compounds like
      guaiacol or creosol, which are indicators of lower quality. CONCLUSION: This
      study brings new insights to vanilla quality control, with a focus on key
      volatile compounds, irrespective of origin.

PMID- 25754310
TI  - PEGylated interferon displays differences in plasma clearance and bioavailability
      between male and female mice and between female immunocompetent C57Bl/6J and
      athymic nude mice.
AB  - Gender and immune status can considerably impact on the pharmacokinetics (PK) of
      macromolecular and small molecule drugs. However, these effects are often not
      considered in drug development. We aimed to quantitatively evaluate effects of
      gender and immune status on the PK of PEGylated interferon in frequently used
      murine models. Chronically cannulated female athymic nude and female and male
      immunocompetent C57Bl/6J mice (n = 24 in total) received a single intravenous or
      subcutaneous (s.c.) dose of PEGylated interferon. Serial blood samples were taken
      for 48 h. Noncompartmental analysis and population PK modeling with covariate
      analysis were performed to evaluate the data. The PK of PEGylated interferon
      followed a three compartment disposition model with two sequential compartments
      for s.c. absorption. Female nude mice had significantly higher plasma clearance
      than C57Bl/6J mice (0.503 vs. 0.397 mL/h). Male mice had a slower absorption rate
      constant (0.138 h(-1)) and extent (46.2%) of s.c. absorption than female mice
      (0.274 in C57Bl/6J and 0.374 h(-1) in nude, 60.8% in both). Thus, gender and
      immune status significantly impacted on important PK parameters of PEGylated
      interferon in murine models commonly utilized in drug development. It is critical
      to take into account these differences when choosing animal models and conducting
      translational pharmacology research.

PMID- 25754311
TI  - Expanded porphyrins: more confusion all the time.

PMID- 25754312
TI  - [Severe acute kidney injury in critically ill children: Epidemiology and
      prognostic factors].
AB  - INTRODUCTION: Acute kidney injury (AKI) is a severe complication in critically
      ill children. The aim of the study was to describe the characteristics of AKI, as
      well as to analyse the prognostic factors for mortality and renal replacement
      therapy (RRT) in children admitted to Paediatric Intensive Care Units (PICUs) in
      Spain. PATIENTS AND METHODS: Prospective observational multicentre study
      including children from 7 days to 16 years old who were admitted to a PICU. A
      univariate and multivariate logistic regression analysis of the risk factors for
      mortality and renal replacement therapy at PICU discharge were performed.
      RESULTS: A total of 139 cases of AKI were analysed. RRT was necessary in 60.1% of
      cases. Mortality rate was 32.6%. At PICU discharge RRT was necessary in 15% of
      survivors. Thrombopenia and low creatinine clearance values were prognostic
      markers of RRT at PICU discharge. High values of platelets, serum creatinine and
      weight were associated with higher survival. CONCLUSIONS: Critically ill children
      with AKI had a high mortality and morbidity rate. Platelet values and creatinine
      clearance are markers of RRT at PICU discharge, whereas number of platelets,
      serum creatinine and weight were associated with mortality.

PMID- 25754313
TI  - [Spanish Society for Pediatric Infectious Diseases guidelines on tuberculosis in
      pregnant women and neonates (i): Epidemiology and diagnosis. Congenital
      tuberculosis].
AB  - Tuberculosis (TB) screening in pregnancy using tuberculin skin test (TST) is
      recommended in case of symptoms of TB disease, close contact with a patient with
      infectious TB, or high risk of developing active disease. The new interferon
      gamma release assay (IGRA) tests are recommended in BCG-vaccinated pregnant women
      with positive TST and no known risk factors for TB, and in those
      immunocompromised, with clinical suspicion of TB but negative TST. TB diagnosis
      is difficult due to the non-specific symptoms, the increased frequency of
      extrapulmonary disease, the delay in radiological examinations, and the high rate
      of tuberculin anergy. Neonatal TB can be acquired in utero (congenital TB), or
      through airborne transmission after delivery (postnatal TB). Congenital TB is
      extremely rare and does not cause fetal malformations. It may be evident at
      birth, although it usually presents after the second week of life. In newborns
      with no family history of TB, the disease should be considered in cases of
      miliary pneumonia, hepatosplenomegaly with focal lesions, or lymphocytic
      meningitis with hypoglycorrhachia, especially in those born to immigrants from
      high TB-burden countries. TST is usually negative, and IGRAs have lower
      sensitivity than in older children. However, the yield of acid-fast smear and
      culture is higher, mostly in congenital TB. Molecular diagnosis techniques enable
      early diagnosis and detection of drug resistance mutations. There is a
      substantial risk of disseminated disease and death. 

PMID- 25754314
TI  - [Spanish Society for Pediatric Infectious Diseases guidelines on tuberculosis in
      pregnant women and neonates (ii): Prophylaxis and treatment].
AB  - In pregnant women who have been exposed to tuberculosis (TB), primary isoniazid
      prophylaxis is only recommended in cases of immunosuppression, chronic medical
      conditions or obstetric risk factors, and close and sustained contact with a
      patient with infectious TB. Isoniazid prophylaxis for latent tuberculosis
      infection (LTBI) is recommended in women who have close contact with an
      infectious TB patient or have risk factors for progression to active disease.
      Otherwise, it should be delayed until at least three weeks after delivery.
      Treatment of TB disease during pregnancy is the same as for the general adult
      population. Infants born to mothers with disseminated or extrapulmonary TB in
      pregnancy, with active TB at delivery, or with postnatal exposure to TB, should
      undergo a complete diagnostic evaluation. Primary isoniazid prophylaxis for at
      least 12 weeks is recommended for those with negative diagnostic tests and no
      evidence of disease. Repeated negative diagnostic tests are mandatory before
      interrupting prophylaxis. Isoniazid for 9 months is recommended in LTBI.
      Treatment of neonatal TB disease is similar to that of older children, but should
      be maintained for at least 9 months. Respiratory isolation is recommended in
      congenital TB, and in postnatal TB with positive gastric or bronchial aspirate
      acid-fast smears. Separation of mother and infant is only necessary when the
      mother has received treatment for less than 2 weeks, is sputum smear-positive, or
      has drug-resistant TB. Breastfeeding is not contraindicated, and in case of
      mother-infant separation expressed breast milk feeding is recommended. 

PMID- 25754315
TI  - Novel, compound heterozygous, single-nucleotide variants in MARS2 associated with
      developmental delay, poor growth, and sensorineural hearing loss.
AB  - Novel, single-nucleotide mutations were identified in the mitochondrial methionyl
      amino-acyl tRNA synthetase gene (MARS2) via whole exome sequencing in two
      affected siblings with developmental delay, poor growth, and sensorineural
      hearing loss.We show that compound heterozygous mutations c.550C>T:p.Gln 184* and
      c.424C>T:p.Arg142Trp in MARS2 lead to decreased MARS2 protein levels in patient
      lymphoblasts. Analysis of respiratory complex enzyme activities in patient
      fibroblasts revealed decreased complex I and IV activities. Immunoblotting of
      patient fibroblast and lymphoblast samples revealed reduced protein levels of
      NDUFB8 and COXII, representing complex I and IV, respectively. Additionally,
      overexpression of wild-type MARS2 in patient fibroblasts increased NDUFB8 and
      COXII protein levels. These findings suggest that recessive single-nucleotide
      mutations in MARS2 are causative for a new mitochondrial translation deficiency
      disorder with a primary phenotype including developmental delay and hypotonia.
      Identification of additional patients with single-nucleotide mutations in MARS2
      is necessary to determine if pectus carinatum is also a consistent feature of
      this syndrome.

PMID- 25754316
TI  - Two giant right coronary artery aneurysms with fistula to the left ventricle:
      preliminary diagnosis by echocardiography.

PMID- 25754317
TI  - Metabolic Dysfunction in Pulmonary Arterial Hypertension.
AB  - Previously considered a disease isolated to the pulmonary circulation, pulmonary
      arterial hypertension is now being recognized as a systemic disorder that is
      associated with significant metabolic dysfunction. Numerous animal models have
      demonstrated the development of pulmonary arterial hypertension following the
      onset of insulin resistance, indicating that insulin resistance may be causal.
      Recent publications highlighting alterations in aerobic glycolysis, fatty acid
      oxidation, and the tricarboxylic acid cycle in the pulmonary circulation and
      right ventricle have expanded our understanding of the complex pathobiology of
      this disease. By targeting these derangements in metabolism, numerous researchers
      are investigating noninvasive techniques to monitor disease activity and
      therapeutics that address the underlying metabolic condition. In the following
      review, we will explore pre-clinical and clinical studies investigating the
      metabolic dysfunction seen in pulmonary arterial hypertension. 

PMID- 25754318
TI  - Understanding the Importance of Race/Ethnicity in the Care of the Hypertensive
      Patient.
AB  - Although several risk factors contribute to cardiovascular disease (CVD) overall,
      hypertension (HTN) is the major controllable risk factor. Hypertension is
      disproportionately more prevalent among Blacks or African-Americans compared with
      other race/ethnic populations, and the control rates among this disparate
      population are alarming. Several pathophysiologic mechanisms have been
      demonstrated and evaluated among hypertensives and the conglomeration of
      genetics, environmental, and personal lifestyle activities concurrently impact
      the progression of hypertension-related comorbidities (i.e., chronic renal
      disease, CVD, stroke, etc.). Specific pharmacotherapeutic choices are discussed
      and the most up-to-date data is presented to optimize the care of hypertensives.
      National and international guidelines for the treatment of HTN are reviewed and
      analyzed, presenting the most appropriate approach to the care of hypertensive
      patients overall. Additionally, national efforts supporting the goal of early HTN
      screening and treatment, as well as the variety of evidence-based
      pharmacotherapy, are summarized, applying to the public health impact overall. 

PMID- 25754319
TI  - Visit-to-Visit Variability of Systolic Blood Pressure and Cardiovascular Disease.
AB  - Visit-to-visit variability of blood pressure (VVV of BP) is gaining interest as a
      prognostic marker for stroke, cardiovascular disease, and all-cause mortality. In
      this review, we discuss different metrics used to define VVV of BP, explore the
      potential sources of this phenomenon including patient characteristics and
      antihypertensive medication classes, and discuss recent evidence of its relation
      with cardiovascular outcomes. Current evidence relies on secondary analyses of
      clinical trials or on observational studies, none of which was designed to
      examine VVV of BP specifically. More research is required to develop standardized
      definitions of VVV of BP, to confirm the value of VVV as a prognostic indicator,
      and to ascertain whether efforts to reduce VVV of BP in addition to mean BP will
      improve outcomes. 

PMID- 25754320
TI  - Renal Denervation in Heart Failure.
AB  - Heart failure has emerged as one of the most important diseases of the past
      century. The understanding and treatment of heart failure has evolved
      significantly over the years. As we move further into the era of device therapy,
      attention has turned to the idea of sympathetic nervous system modulation through
      renal denervation to treat heart failure. In this review, we summarize the
      background research, denervation technique, and current studies on renal
      denervation for the treatment of heart failure. We also compare and contrast the
      work on carotid barostimulation. 

PMID- 25754321
TI  - The Western Diet and Chronic Kidney Disease.
AB  - Characteristics of the Western diet that fueled the obesity epidemic may also
      impact kidney disease incidence and progression. Enlarging portion sizes over the
      past half century has been accompanied by increased intake of protein, sodium,
      and processed foods while consumption of fruits and vegetables has declined.
      Overall dietary patterns play a strong role for chronic disease risk including
      chronic kidney disease. While dietary patterns high in fresh fruits and
      vegetables and low in red meats, such as the Mediterranean diet, decrease the
      risk of chronic diseases, the Western diet, characterized by high intake of red
      meat, animal fat, sweets, and desserts and low intake of fresh fruits and
      vegetables and low-fat dairy products, increases risk of chronic diseases. In
      this article, we review the potential mechanisms whereby several key
      characteristics of the typical Western diet may impact kidney disease incidence
      and progression. We also discuss a public health policy initiative to improve
      dietary choices. Reducing protein intake to the recommended daily allowance of
      0.8 g/kg/day and increasing intake of fruit and vegetables and fiber may mitigate
      kidney disease progression and reduce risk of cardiovascular disease and
      mortality. 

PMID- 25754322
TI  - Natriuretic Peptides as a Novel Target in Resistant Hypertension.
AB  - Resistant hypertension is defined as blood pressure not under goal despite being
      on at least three antihypertensives. Resistant hypertension is associated with
      significant cardiovascular morbidity and mortality. Currently, the mainstay for
      the treatment of resistant hypertension is lifestyle modification and
      antihypertensive drugs. Natriuretic peptides play an important role in regulating
      cardiovascular hemodynamics and sodium and fluid homeostasis including blood
      pressure control. They hold a promising potential for treatment of resistant
      hypertension. 

PMID- 25754323
TI  - The Baroreflex in Hypertension.
AB  - Hypertension is a complex syndrome that increases the risk of developing other
      medical comorbidities and interacts with other medical conditions to increase the
      risk of target end-organ damage such as cardiovascular disease, stroke, and renal
      disease. Hypertension remains under-recognized and poorly controlled in the USA
      and worldwide. In some patients, hypertension is resistant to optimal medical
      therapy. Over the last few decades, there has been an increasing understanding of
      the role of the sympathetic nervous system in the development and maintenance of
      hypertension. This update reviews the physiology and role of the sympathetic
      nervous system in hypertension and pharmacological and interventional treatments
      directed at nervous system involvement in secondary hypertension. 

PMID- 25754324
TI  - Use of clean intermittent self-catheterization in France: A survey of patient and
      GP perspectives.
AB  - AIMS: To estimate the prevalence of GP (general practitioner) patients performing
      ISC (intermittent self-catheterization), to describe GP and patient knowledge
      about ISC and to assess the patients' quality of life. METHODS: A cross-sectional
      study was conducted in metropolitan France between November 2012 and September
      2013 with French Sentinelles GPs and their patients (>=18 years) performing ISC.
      Linear regression models assessed independent associations between quality of
      life scores (Qualiveen and SF-12 scores) and patients' characteristics. RESULTS:
      The prevalence of ISC performers was estimated to be 61.7 (95% confidence
      interval [CI] = 61.0-62.4) of 100,000 inhabitants. Patients were males in 58.8%
      of cases and 53.8 years of age on average. They performed 4.84 catheterizations
      per day for 10.5 years. Over 1 year, there were 118 (55.1%) cases of patient
      reported urinary incontinence (UI) and 158 (63.3%) cases of patient-reported
      urinary tract infection (UTI). Symptomatic UTIs were treated with antibiotics in
      79.7% of cases. The average Qualiveen score was 1.38 (95%CI: 1.23-1.53). The
      average SF-12 Physical Component Score (PCS) and Mental Component Score (MCS)
      were 38.6 (95%CI: 36.8-40.4) and 46.4 (95%CI: 44.3-48.5), respectively. According
      to multivariate analysis, a poorer Qualiveen score and constipation reduced the
      PCS and a urinary medication prescription reduced the MCS. A poorer Qualiveen
      score was also associated with UI and UTI on bivariate analysis. CONCLUSIONS: ISC
      seems to be significant in French general practice whereas practical skills
      remain heterogeneous. UI, UTI, and constipation are recurrent issues among ISC
      performers that significantly decrease their quality of life. Education and
      adapted guidelines for GP guidance could improve these patients' conditions.
      Neurourol. Urodynam. 35:528-534, 2016. (c) 2015 Wiley Periodicals, Inc.

PMID- 25754325
TI  - A whole-of-population study of term and post-term gestational age at birth and
      children's development.
AB  - OBJECTIVE: To examine the risk of poor child development according to week of
      gestation at birth, among children born >= 37 weeks' gestation. DESIGN:
      Population-based study using linked data (n = 12,601). SETTING: South Australia.
      POPULATION: All births >= 37 weeks' gestation. METHODS: Relative risks of
      developmental vulnerability for each week of gestation were calculated with
      adjustment for confounders and addressing missing information. MAIN OUTCOME
      MEASURES: Child development was documented by teachers during a national census
      of children attending their first year of school in 2009, using the Australian
      Early Development Index (AEDI). Children scoring in the lowest 10% of the AEDI
      were categorised as developmentally vulnerable. RESULTS: The percentage of
      children vulnerable on one or more AEDI domains for the following gestational
      ages 37, 38, 39, 40, 41, 42-45 weeks was 24.8, 22.3, 20.6, 20.0, 20.4 and 24.2,
      respectively. Compared with children born at 40 weeks, the adjusted relative
      risks [(95% confidence interval (CI)] for vulnerability on >= 1 AEDI domain were;
      37 weeks 1.13 (0.99-1.28), 38 weeks 1.05 (0.96-1.15), 39 weeks 1.02 (0.94-1.12),
      41 weeks 1.00 (0.90-1.11) and 42-45 weeks 1.20 (0.84-1.72). CONCLUSIONS: Children
      born at 40-41 weeks' gestation may have the lowest risk of developmental
      vulnerability at school entry, reinforcing the importance of term birth in
      perinatal care. Early term or post-term gestational age at birth can help
      clinicians, teachers and parents recognise children with potential developmental
      vulnerabilities at school entry.

PMID- 25754326
TI  - Current perspectives on physical activity and exercise for youth with diabetes.
AB  - Regular physical activity (PA) for youth with diabetes improves cardiorespiratory
      fitness, body composition, bone health, insulin sensitivity, and psychosocial
      well-being. However many youth with diabetes or pre-diabetes fail to meet minimum
      PA guidelines and a large percentage of youth with diabetes are overweight or
      obese. Active youth with type 1 diabetes tend to have lower HbA1c levels and
      reduced insulin needs, whereas activity in adolescents at-risk for type 2
      diabetes improves various measures of metabolism and body composition. Insulin
      and nutrient adjustments for exercise in type 1 diabetes is complex because of
      varied responses to exercise type and because of the different times of day that
      exercise is performed. This review highlights the benefits of exercise and the
      established barriers to exercise participation in the pediatric diabetes
      population. A new exercise management algorithm for insulin and carbohydrate
      intake strategies for active youth with type 1 diabetes is presented. 

PMID- 25754327
TI  - Cost-effectiveness analysis of mometasone furoate versus beclomethasone
      dipropionate for the treatment of pediatric allergic rhinitis in Colombia.
AB  - INTRODUCTION: Allergic rhinitis (AR) is one of the most common chronic
      respiratory diseases observed in the pediatric population, producing a
      significant morbidity, and an economic burden due to direct medical costs and
      indirect costs. Despite the high prevalence of AR in children and the importance
      of the use of topical intranasal corticosteroids for its treatment, comparative
      analyses of alternative treatments in pediatric patients, in terms of both cost
      and effectiveness are lacking. METHODS: A decision-analysis model was developed
      to estimate the cost-effectiveness of mometasone furoate nasal spray (MFNS)
      compared to beclomethasone dipropionate nasal spray (BDNS) for treating pediatric
      patients with AR over a 12-month period. Effectiveness parameters were obtained
      from a published study in which authors performed a systematic review of the
      literature. Cost data were obtained from a hospital's bills and from the national
      manual of drug prices. The study assumed the perspective of the national
      healthcare in Colombia. The outcomes were three effectiveness measures summarized
      in a therapeutic index (TIX). RESULTS: For the base-case analysis, the model
      showed that compared to BDNS, therapy with MFNS was associated with lower costs
      (US$229.78 vs. 289.74 average cost per patient over 12 months) and a greater
      improvement in TIX score (0.9724 vs. 0.8712 score points on average per patient
      over 12 months), thus leading to dominance. CONCLUSION: The present analysis
      shows that in Colombia, compared with BDNS, therapy with MFNS for treating
      pediatric patients with AR is a dominant strategy because it showed a greater
      improvement in a TIX reflecting both efficacy and safety, at lower total
      treatment costs.

PMID- 25754328
TI  - Ligand-enabled meta-C-H activation using a transient mediator.
AB  - Achieving site selectivity in C-H functionalization reactions is a significant
      challenge, especially when the target C-H bond is distant from existing
      functional groups. Coordination of a functional group to a metal is often a key
      driving force and control element in many important reactions including
      asymmetric hydrogenation, epoxidation and lithiation. Exploitation of this effect
      has led to the development of a broad range of directed C-H activation reactions.
      However, these C-H activation methods are limited to proximal C-H bonds, which
      are spatially and geometrically accessible from the directing functional group.
      The development of meta-selective C-H functionalizations remains a significant
      challenge. We recently developed a U-shaped template that can be used to overcome
      this constraint and have shown that it can be used to selectively activate remote
      meta-C-H bonds. Although this approach has proved to be applicable to various
      substrates and catalytic transformations, the need for a covalently attached,
      complex template is a substantial drawback for synthetic applications. Here we
      report an alternative approach employing norbornene as a transient mediator to
      achieve meta-selective C-H activation with a simple and common ortho-directing
      group. The use of a newly developed pyridine-based ligand is crucial for relaying
      the palladium catalyst to the meta position by norbornene after initial ortho-C-H
      activation. This catalytic reaction demonstrates the feasibility of switching
      ortho-selectivity to meta-selectivity in C-H activation of the same substrate by
      catalyst control. 

PMID- 25754330
TI  - Clinical improvement in psoriasis with specific targeting of interleukin-23.
AB  - Psoriasis is a chronic inflammatory skin disorder that affects approximately 2-3%
      of the population worldwide and has severe effects on patients' physical and
      psychological well-being. The discovery that psoriasis is an immune-mediated
      disease has led to more targeted, effective therapies; recent advances have
      focused on the interleukin (IL)-12/23p40 subunit shared by IL-12 and IL-23.
      Evidence suggests that specific inhibition of IL-23 would result in improvement
      in psoriasis. Here we evaluate tildrakizumab, a monoclonal antibody that targets
      the IL-23p19 subunit, in a three-part, randomized, placebo-controlled,
      sequential, rising multiple-dose phase I study in patients with moderate-to
      severe psoriasis to provide clinical proof that specific targeting of IL-23p19
      results in symptomatic improvement of disease severity in human subjects. A 75%
      reduction in the psoriasis area and severity index (PASI) score (PASI75) was
      achieved by all subjects in parts 1 and 3 (pooled) in the 3 and 10 mg kg(-1)
      groups by day 196. In part 2, 10 out of 15 subjects in the 3 mg kg(-1) group and
      13 out of 14 subjects in the 10 mg kg(-1) group achieved a PASI75 by day 112.
      Tildrakizumab demonstrated important clinical improvement in moderate-to-severe
      psoriasis patients as demonstrated by improvements in PASI scores and
      histological samples. 

PMID- 25754329
TI  - Radiation and dual checkpoint blockade activate non-redundant immune mechanisms
      in cancer.
AB  - Immune checkpoint inhibitors result in impressive clinical responses, but optimal
      results will require combination with each other and other therapies. This raises
      fundamental questions about mechanisms of non-redundancy and resistance. Here we
      report major tumour regressions in a subset of patients with metastatic melanoma
      treated with an anti-CTLA4 antibody (anti-CTLA4) and radiation, and reproduced
      this effect in mouse models. Although combined treatment improved responses in
      irradiated and unirradiated tumours, resistance was common. Unbiased analyses of
      mice revealed that resistance was due to upregulation of PD-L1 on melanoma cells
      and associated with T-cell exhaustion. Accordingly, optimal response in melanoma
      and other cancer types requires radiation, anti-CTLA4 and anti-PD-L1/PD-1. Anti
      CTLA4 predominantly inhibits T-regulatory cells (Treg cells), thereby increasing
      the CD8 T-cell to Treg (CD8/Treg) ratio. Radiation enhances the diversity of the
      T-cell receptor (TCR) repertoire of intratumoral T cells. Together, anti-CTLA4
      promotes expansion of T cells, while radiation shapes the TCR repertoire of the
      expanded peripheral clones. Addition of PD-L1 blockade reverses T-cell exhaustion
      to mitigate depression in the CD8/Treg ratio and further encourages oligoclonal T
      cell expansion. Similarly to results from mice, patients on our clinical trial
      with melanoma showing high PD-L1 did not respond to radiation plus anti-CTLA4,
      demonstrated persistent T-cell exhaustion, and rapidly progressed. Thus, PD-L1 on
      melanoma cells allows tumours to escape anti-CTLA4-based therapy, and the
      combination of radiation, anti-CTLA4 and anti-PD-L1 promotes response and
      immunity through distinct mechanisms. 

PMID- 25754331
TI  - Seven novel modulators of the analgesic target NaV 1.7 uncovered using a high
      throughput venom-based discovery approach.
AB  - BACKGROUND AND PURPOSE: Chronic pain is a serious worldwide health issue, with
      current analgesics having limited efficacy and dose-limiting side effects. Humans
      with loss-of-function mutations in the voltage-gated sodium channel NaV 1.7 (hNaV
      1.7) are indifferent to pain, making hNaV 1.7 a promising target for analgesic
      development. Since spider venoms are replete with NaV channel modulators, we
      examined their potential as a source of hNaV 1.7 inhibitors. EXPERIMENTAL
      APPROACH: We developed a high-throughput fluorescent-based assay to screen spider
      venoms against hNaV 1.7 and isolate 'hit' peptides. To examine the binding site
      of these peptides, we constructed a panel of chimeric channels in which the S3b
      S4 paddle motif from each voltage sensor domain of hNaV 1.7 was transplanted into
      the homotetrameric KV 2.1 channel. KEY RESULTS: We screened 205 spider venoms and
      found that 40% contain at least one inhibitor of hNaV 1.7. By deconvoluting 'hit'
      venoms, we discovered seven novel members of the NaSpTx family 1. One of these
      peptides, Hd1a (peptide MU-TRTX-Hd1a from venom of the spider Haplopelma doriae),
      inhibited hNaV 1.7 with a high level of selectivity over all other subtypes,
      except hNaV 1.1. We showed that Hd1a is a gating modifier that inhibits hNaV 1.7
      by interacting with the S3b-S4 paddle motif in channel domain II. The structure
      of Hd1a, determined using heteronuclear NMR, contains an inhibitor cystine knot
      motif that is likely to confer high levels of chemical, thermal and biological
      stability. CONCLUSION AND IMPLICATIONS: Our data indicate that spider venoms are
      a rich natural source of hNaV 1.7 inhibitors that might be useful leads for the
      development of novel analgesics.

PMID- 25754332
TI  - Botulinum neurotoxin type A modulates vesicular release of glutamate from
      satellite glial cells.
AB  - This study investigated the presence of cell membrane docking proteins
      synaptosomal-associated protein, 25 and 23 kD (SNAP-25 and SNAP-23) in satellite
      glial cells (SGCs) of rat trigeminal ganglion; whether cultured SGCs would
      release glutamate in a time- and calcium-dependent manner following calcium
      ionophore ionomycin stimulation; and if botulinum neurotoxin type A (BoNTA), in a
      dose-dependent manner, could block or decrease vesicular release of glutamate.
      SGCs were isolated from the trigeminal ganglia (TG) of adult Wistar rats and
      cultured for 7 days. The presence of SNAPs in TG sections and isolated SGCs were
      investigated using immunohistochemistry and immunocytochemistry, respectively.
      SGCs were stimulated with ionomycin (5 MUM for 4, 8, 12 and 30 min.) to release
      glutamate. SGCs were then pre-incubated with BoNTA (24 hrs with 0.1, 1, 10 and
      100 pM) to investigate if BoNTA could potentially block ionomycin-stimulated
      glutamate release. Glutamate concentrations were measured by ELISA. SNAP-25 and
      SNAP-23 were present in SGCs in TG sections and in cultured SGCs. Ionomycin
      significantly increased glutamate release from cultured SGCs 30 min. following
      the treatment (P < 0.001). BoNTA (100 pM) significantly decreased glutamate
      release (P < 0.01). Results from this study demonstrated that SGCs, when
      stimulated with ionomycin, released glutamate that was inhibited by BoNTA,
      possibly through cleavage of SNAP-25 and/or SNAP-23. These novel findings
      demonstrate the existence of vesicular glutamate release from SGCs, which could
      potentially play a role in the trigeminal sensory transmission. In addition,
      interaction of BoNTA with non-neuronal cells at the level of TG suggests a
      potential analgesic mechanism of action of BoNTA.

PMID- 25754334
TI  - The 2009/2010 Caribbean drought: a case study.
AB  - The impacts of drought in the Caribbean have not been as dramatic as in some
      other parts of world, but it is not exempt from the experiences of drought. As a
      result of the effects of a prolonged drought in 2009/2010, the agenda for the
      21st Inter-Sessional Meeting of the Caribbean Community (CARICOM) paid particular
      attention to the issue of drought. This paper reviews the management framework
      for responding to drought disasters in five CARICOM countries. The paper also
      reports on some of the effects of the 2009/2010 drought with particular reference
      to Grenada and the Grenadines. During the drought in these islands there were
      numerous bush fires with devastating effects on agriculture, severe water
      shortages that impacted on the tourism industry and other social effects. It is
      evident that there was inadequate preparation for the event. Greater planning and
      investment are therefore required to reduce future impacts. 

PMID- 25754333
TI  - Alcoholic hepatitis and HCV interactions in the modulation of liver disease.
AB  - Most HCV-infected patients regularly consume alcohol. Alcoholic liver disease
      (ALD) and chronic hepatitis C virus (HCV) infection together are the most common
      causes of liver disease worldwide. Although both factors independently cause
      liver disease, they synergistically promote rapid liver disease progression with
      devastating outcomes for patients. This review focuses on the prevalence,
      clinical characteristics and molecular pathophysiologic mechanisms of HCV
      infection associated with alcohol abuse. Recent findings have centred on the
      synergistic effect of alcohol and HCV on viral replication, hepatocyte apoptosis,
      oxidative stress, alcohol-induced 'leaky gut', miR-122 and immune dysregulation.
      Clinical and basic research findings presented here summarize key scientific
      findings with the aim of highlighting potential areas for new therapies and
      identifying ways of optimizing current treatments for alcoholics with HCV
      infection. 

PMID- 25754336
TI  - Imaging shear stress distribution and evaluating the stress concentration factor
      of the human eye.
AB  - Healthy eyes are vital for a better quality of human life. Historically, for man
      made materials, scientists and engineers use stress concentration factors to
      characterise the effects of structural non-homogeneities on their mechanical
      strength. However, such information is scarce for the human eye. Here we present
      the shear stress distribution profiles of a healthy human cornea surface in vivo
      using photo-stress analysis tomography, which is a non-intrusive and non-X-ray
      based method. The corneal birefringent retardation measured here is comparable to
      that of previous studies. Using this, we derive eye stress concentration factors
      and the directional alignment of major principal stress on the surface of the
      cornea. Similar to thermometers being used for monitoring the general health in
      humans, this report provides a foundation to characterise the shear stress
      carrying capacity of the cornea, and a potential bench mark for validating
      theoretical modelling of stresses in the human eye in future. 

PMID- 25754335
TI  - Rheumatoid arthritis is sufficient to cause atheromatosis but not arterial
      stiffness or hypertrophy in the absence of classical cardiovascular risk factors.
AB  - Rheumatoid arthritis (RA) associates with increased cardiovascular disease (CVD)
      mortality thought to be due to accelerated arterial disease. Different components
      of arterial disease, namely, atheromatosis, arteriosclerosis, and arterial wall
      hypertrophy, are differentially affected by classical CVD risk factors, which are
      highly prevalent in these patients. We hypothesized that RA disease per se may
      also differentially affect these components. Of 267 consecutive RA patients, we
      selected specifically those who were free of established CVD and CVD risk factors
      (18 %); of them, 41 patients (36 women, 49 +/- 13 years) could be matched
      effectively 1:1 for age and gender to healthy controls. Atheromatosis was
      assessed by the presence of carotid and/or femoral artery plaques,
      arteriosclerosis by pulse wave velocity and local wall elasticity, and arterial
      hypertrophy by intima-media thickness and cross-sectional area. More patients had
      atheromatic plaques than controls (29 vs. 12 %, p = 0.039), and multiarterial
      atheromatosis was more prevalent in RA (22 vs. 2 %, p = 0.026). Accelerated
      atheromatosis was not associated with rheumatoid factor, or anti-cyclic
      citrullinated peptide (CCP) autoantibody status. Plaque burden in patients with
      less than 5 years disease duration (aged 41 +/- 13 years) was comparable to their
      matched controls. In contrast, all indices of arterial stiffness and hypertrophy
      were similar between controls and RA patients, even in those with long-standing
      disease. RA per se is sufficient to cause atheromatosis in the absence of
      classical CVD risk factors, but has minimal, if any, effect on arteriosclerosis
      and arterial wall hypertrophy.

PMID- 25754337
TI  - Factors influencing the regioselectivity of the oxidation of asymmetric secondary
      amines with singlet oxygen.
AB  - Aerobic amine oxidation is an attractive and elegant process for the alpha
      functionalization of amines. However, there are still several mechanistic
      uncertainties, particularly the factors governing the regioselectivity of the
      oxidation of asymmetric secondary amines and the oxidation rates of mixed primary
      amines. Herein, it is reported that singlet-oxygen-mediated oxidation of 1
      degrees  and 2 degrees  amines is sensitive to the strength of the alpha-C-H bond
      and steric factors. Estimation of the relative bond dissociation energy by
      natural bond order analysis or by means of one-bond C-H coupling constants
      allowed the regioselectivity of secondary amine oxidations to be explained and
      predicted. In addition, the findings were utilized to synthesize highly
      regioselective substrates and perform selective amine cross-couplings to produce
      imines.

PMID- 25754338
TI  - Prefrontal Gamma Oscillations Encode Tonic Pain in Humans.
AB  - Under physiological conditions, momentary pain serves vital protective functions.
      Ongoing pain in chronic pain states, on the other hand, is a pathological
      condition that causes widespread suffering and whose treatment remains
      unsatisfactory. The brain mechanisms of ongoing pain are largely unknown. In this
      study, we applied tonic painful heat stimuli of varying degree to healthy human
      subjects, obtained continuous pain ratings, and recorded electroencephalograms to
      relate ongoing pain to brain activity. Our results reveal that the subjective
      perception of tonic pain is selectively encoded by gamma oscillations in the
      medial prefrontal cortex. We further observed that the encoding of subjective
      pain intensity experienced by the participants differs fundamentally from that of
      objective stimulus intensity and from that of brief pain stimuli. These
      observations point to a role for gamma oscillations in the medial prefrontal
      cortex in ongoing, tonic pain and thereby extend current concepts of the brain
      mechanisms of pain to the clinically relevant state of ongoing pain. Furthermore,
      our approach might help to identify a brain marker of ongoing pain, which may
      prove useful for the diagnosis and therapy of chronic pain. 

PMID- 25754339
TI  - Archives and skeletons: An interdisciplinary approach to the study of
      paleopathology of tuberculosis.
AB  - Tuberculosis (TB) may be an acute or chronic infection of bone and/or soft
      tissues. Nevertheless, human skeletons only registered a small percentage of
      those cases. This work aims to explore data from morbidity and mortality of
      individuals who contracted or died of TB after Koch bacillus discovery and before
      the development of antibiotics, using this information to interpret the scarcity
      of evidences detectable by paleopathological studies. To fulfill these goals, the
      Coimbra University Hospital and Coimbra Municipality Cemetery records from 1919
      to 1928 were analyzed. As expected, pulmonary TB was the most common form of the
      diseases, both at hospital admission (43.7%, n=904) and as cause of death of the
      individuals inhumed, especially after the age of 10 years. In children under 10
      years, meningeal TB was the more common form. Pott's diseases represented only
      4.7% (n=98) of the hospital admission due to TB and 0.7% (n=8) of the TB deaths
      at the cemetery. However, in paleopathology the macroscopic evidence of TB comes
      mainly from Pott's disease. Documented skeletons shows that new bone on visceral
      surfaces of ribs can occurs in other diseases besides pulmonary TB but its
      presence can be also use as an indicative of possible TB infection.

PMID- 25754340
TI  - Three-dimensional imaging of past skeletal TB: From lesion to process.
AB  - 3D imaging has become an essential tool in the field of biological anthropology,
      notably for human evolution purposes. High resolution virtual 3D reconstructions
      of original specimens contribute to their preservation and broaden the ability
      for research, teaching and exchanges. Paleopathology can get substantial benefit
      from these methods, among others for reconstructing infectious pathological
      processes on ancient bones. Tuberculosis is frequently diagnosed on ancient human
      remains; however, some osseous expressions are difficult to interpret using
      classical methods. We illustrate here the interest of 3D methods for
      reconstructing processes involved in pathological bone changes due to
      Mycobacterium tuberculosis infection. Four paleopathological specimens attributed
      to this infection, dating from different time periods and concerning diverse
      parts of the skeleton have been analyzed using a specific 3D digital chain we
      have previously developed. These 3D analyses allow to virtually reconstruct the
      initial location and aspect of the infectious process, its extension as well as
      its possible diffusion to the surrounding soft tissues. This possible virtual
      follow-up of the disease leads to the concept of processual paleopathology that
      we would like to introduce in the field. The 3D methodology can help to improve
      our knowledge of natural history and evolution of ancient human infections such
      as tuberculosis. 

PMID- 25754341
TI  - Evidence for tuberculosis in 18th/19th century slaves in Anse Sainte-Marguerite
      (Guadeloupe - French Western Indies).
AB  - During the American colonization in the 18th and 19th century, Africans were
      captured and shipped to America. Harsh living and working conditions often led to
      chronic diseases and high mortality rates. Slaves in the Caribbean were forced to
      work mainly on sugar plantations. They were buried in cemeteries like Anse Sainte
      Marguerite on the isle of Grande-Terre (Guadeloupe) which was examined by
      archaeologists and physical anthropologists. Morphological studies on osseous
      remains of 148 individuals revealed 15 cases with signs for bone tuberculosis and
      a high frequency of periosteal reactions which indicates early stages of the
      disease. 11 bone samples from these cemeteries were analysed for ancient DNA. The
      samples were extracted with established procedures and examined for the
      cytoplasmic multicopy beta-actin gene and Mycobacterium tuberculosis complex DNA
      (IS 6110) by PCR. An amplification product for M. tuberculosis with the size of
      123 bp was obtained. Sequencing confirmed the result. This study shows evidence
      of M. tuberculosis complex DNA in a Caribbean slave population.

PMID- 25754342
TI  - Mycobacterium tuberculosis phylogeography in the context of human migration and
      pathogen's pathobiology: Insights from Beijing and Ural families.
AB  - Here, I review the population structure and phylogeography of the two contrasting
      families of Mycobacterium tuberculosis, Beijing and Ural, in the context of
      strain pathobiology and human history and migration. Proprietary database (12
      loci MIRU-VNTR profiles of 3067 Beijing genotype isolates) was subjected to
      phylogenetic and statistical analysis. The highest rate (90%) and diversity (HGI
      0.80-0.95) of the Beijing genotype in North China suggest it to be its area of
      origin. Under VNTR-based MDS analysis the interpopulation genetic distances
      correlated with geography over uninterrupted landmasses. In contrast, large water
      distances together with long time generated remarkable outliers. Weak and less
      expected affinities of the distant M. tuberculosis populations may reflect hidden
      epidemiological links due to unknown migration. Association with drug-resistance
      or increased virulence/transmissibility along with particular human migration
      flows shape global dissemination of some Beijing clones. The paucity of data on
      the Ural genotype prevents from high-resolution analysis that was mainly based on
      the available spoligotyping data. The North/East Pontic area marked with the
      highest prevalence of the Ural family may have been the area of its origin and
      primary dispersal in Eurasia. Ural strains are not marked by increased pathogenic
      capacities, increased transmissibility and association with drug resistance (but
      most recent reports describe an alarming increase of MDR Ural strains in some
      parts of eastern Europe and northwestern Russia). Large-scale SNP or WGS
      population-based studies targeting strains from indigenous populations and,
      eventually, analysis of ancient DNA will better test these hypotheses. Host
      genetics factors likely play the most prominent role in differential
      dissemination of particular M. tuberculosis genotypes. 

PMID- 25754343
TI  - Ridge preservation after ridge expansion with simultaneous guided bone
      regeneration: a preclinical study.
AB  - OBJECTIVE: To evaluate ridge preservation after ridge splitting with simultaneous
      implant placement and guided bone regeneration (GBR) in a miniature pig model.
      MATERIAL AND METHODS: In miniature pigs, the mandibular premolars and first
      molars were extracted together with removal of the interdental and buccal bone.
      Three months later, ridge splitting and expansion of the buccal plate were
      performed with simultaneous placement of two titanium implants per quadrant. On
      the test side, access by a mucoperiosteal flap followed by GBR with a biphasic
      calcium phosphate and a collagen membrane was performed. On the contralateral
      control side, a mucosal flap (MF), leaving the periosteum attached to the buccal
      bone, was elevated. After healing periods of 6 and 12 weeks, eight and four
      animals, respectively, were sacrificed for histological and histometric
      evaluation. RESULTS: In the MF group, all 16 implants were osseointegrated, while
      in the GBR group, one bone fracture occurred, and six of 16 implants were lost.
      After 6 weeks, significantly higher bone crest levels were found for the GBR
      group than for the MF group both buccally and lingually (P < 0.001), and buccal
      bone thickness was greater in the GBR group than in the MF group (P < 0.001 at
      the implant shoulder [IS]). After 12 weeks, bone was significantly higher in the
      GBR group compared to the MF group. Furthermore, buccal bone thickness in the GBR
      group was 0.93, 4.5, and 5.94 mm at, and 2 and 4 mm apical to the IS,
      respectively. The corresponding values in the MF group were greatly reduced (0,
      0.21, and 2.56 mm). Bone loss on the buccal side compared to the lingual side was
      significantly greater only in the MF group. CONCLUSIONS: In this ridge expansion
      model in miniature pigs, the buccal bone volume was significantly better
      preserved with GBR when compared to a mucosal access flap, provided that soft
      tissue healing occurred complication free.

PMID- 25754344
TI  - Empowering a transition-metal-free coupling between alkyne and alkyl iodide with
      light in water.
AB  - Methods to assemble alkynes are essential for synthesizing fine chemicals,
      pharmaceuticals and polymeric photo-/electronic materials. Using light as a clean
      energy form and water as a green solvent has the potential to make synthetic
      chemistry more environmentally friendly. Here we present a transition-metal-free
      coupling protocol between aryl alkyne and alkyl iodide enabled by photoenergy in
      water. Under ultraviolet irradiation and in basic aqueous media, aryl alkynes
      efficiently couple with a wide range of alkyl iodides including primary,
      secondary and tertiary ones under mild conditions. A tentative mechanism for the
      coupling is also proposed. 

PMID- 25754345
TI  - HLA-DRB1 mismatch is associated with a decreased relapse in adult acute myeloid
      leukemia after single-unit myeloablative cord blood transplantation.

PMID- 25754346
TI  - Expedient synthesis of pyrroloquinolinones by Rh-catalyzed annulation of N
      carbamoyl indolines with alkynes through a directed C-H functionalization/C-N
      cleavage sequence.
AB  - A Rh-catalyzed redox-neutral C-H functionalization of N-carbamoyl indolines with
      various internal alkynes has been developed. The reaction, which involves the
      sequential cleavage of the C-H bond of the indoline at the C7-position and the C
      N bond of the urea motif, provides a divergent protocol to rapidly assemble fused
      ring pyrroloquinolinone analogues by using a direct alkenylation/annulation
      strategy with high efficiency and selectivity. 

PMID- 25754347
TI  - ERG/AKR1C3/AR Constitutes a Feed-Forward Loop for AR Signaling in Prostate Cancer
      Cells.
AB  - PURPOSE: Intratumoral androgen synthesis in prostate cancer contributes to the
      development of castration-resistant prostate cancer (CRPC). Several enzymes
      responsible for androgen biosynthesis have been shown to be overexpressed in
      CRPC, thus contributing to CRPC in a castrated environment. The TMPRSS2-ERG
      transcription factor has been shown to be present in primary prostate cancer
      tumors as well as CRPC tumors. We hypothesize that TMPRSS2-ERG fusions regulate
      androgen biosynthetic enzyme (ABE) gene expression and the production of
      androgens, which contributes to the development of CRPC. EXPERIMENTAL DESIGN: We
      used a panel of assays, including lentivirus transduction, gene expression,
      chromatin immunoprecipitation and sequencing, liquid chromatography-mass
      spectrometric quantitation, immunocytochemistry, immunohistochemistry, and
      bioinformatics analysis of gene microarray databases, to determine ERG regulation
      of androgen synthesis. RESULTS: We found that ERG regulated the expression of the
      ABE AKR1C3 in prostate cancer cells via direct binding to the AKR1C3 gene.
      Knockdown of ERG resulted in reduced AKR1C3 expression, which caused a reduction
      in both DHT synthesis and PSA expression in VCaP prostate cancer cells treated
      with 5alpha-androstanedione (5alpha-Adione), a DHT precursor metabolite.
      Immunohistochemical staining revealed that ERG was coexpressed with AKR1C3 in
      prostate cancer tissue samples. CONCLUSIONS: These data suggest that AKR1C3
      catalyzes the biochemical reduction of 5alpha-Adione to DHT in prostate cancer
      cells, and that ERG regulates this step through upregulation of AKR1C3
      expression. Elucidation of ERG regulation of ABEs in CRPC may help to stratify
      TMPRSS2-ERG fusion-positive prostate cancer patients in the clinic for anti
      androgen receptor-driven therapies; and AKR1C3 may serve as a valuable
      therapeutic target in the treatment of CRPC.

PMID- 25754348
TI  - FDA approval: ceritinib for the treatment of metastatic anaplastic lymphoma
      kinase-positive non-small cell lung cancer.
AB  - On April 29, 2014, the FDA granted accelerated approval to ceritinib (ZYKADIA;
      Novartis Pharmaceuticals Corporation), a breakthrough therapy-designated drug,
      for the treatment of patients with anaplastic lymphoma kinase (ALK)-positive,
      metastatic non-small cell lung cancer (NSCLC) who have progressed on or are
      intolerant to crizotinib. The approval was based on a single-arm multicenter
      trial enrolling 163 patients with metastatic ALK-positive NSCLC who had disease
      progression on (91%) or intolerance to crizotinib. Patients received ceritinib at
      a starting dose of 750 mg orally once daily. The objective response rate (ORR) by
      a blinded independent review committee was 44% (95% CI, 36-52), and the median
      duration of response (DOR) was 7.1 months. The ORR by investigator assessment was
      similar. Safety was evaluated in 255 patients. The most common adverse reactions
      and laboratory abnormalities included diarrhea (86%), nausea (80%), increased
      alanine transaminase (80%), increased aspartate transaminase (75%), vomiting
      (60%), increased glucose (49%), and increased lipase (28%). Although 74% of
      patients required at least one dose reduction or interruption due to adverse
      reactions, the discontinuation rate due to adverse reactions was low (10%). With
      this safety profile, the benefit-risk analysis was considered favorable because
      of the clinically meaningful ORR and DOR.

PMID- 25754350
TI  - Is this the time to introduce minimal residual disease in multiple myeloma
      clinical practice?
AB  - Increasing therapeutic options and prolonged survival in multiple myeloma have
      raised interest in the concept of depth of response and its importance to predict
      patients' outcomes. Although the efficacy of current treatment approaches has
      greatly improved in the past decade, the definition of complete response (CR)
      remains unaltered and continues to use conventional serological and morphologic
      techniques. That notwithstanding, there is growing interest in minimal residual
      disease (MRD) monitoring, which has emerged in recent years as one of the most
      relevant prognostic factors in multiple myeloma. MRD can be assessed both inside
      (e.g., immunophenotypic and molecular techniques) and outside the bone marrow
      (e.g., PET/CT). Here, we focus on flow- and molecular-based assays by which
      different cooperative groups have demonstrated the efficacy of MRD assessment to
      predict outcomes even among patients in CR, and irrespectively of disease risk.
      Although further standardization is still required, the time has come to
      implement MRD monitoring in prospective clinical trials as a sensitive tool to
      evaluate treatment efficacy and for risk-adapted treatment, particularly in the
      consolidation and maintenance settings. Here, we present a comprehensive and
      critical review on the methodologic aspects, specific characteristics, and
      clinical significance of MRD monitoring by flow cytometry, PCR, and next
      generation sequencing.

PMID- 25754349
TI  - Elucidation of Acquired Resistance to Bcl-2 and MDM2 Inhibitors in Acute Leukemia
      In Vitro and In Vivo.
AB  - PURPOSE: Two clinical-stage anticancer drugs, the Bcl-2 inhibitor ABT-263, and
      the MDM2 inhibitor SAR405838 achieve complete tumor regression in animal models
      of leukemia but also induce acquired resistance. Elucidation of acquired
      resistance mechanisms and development of strategies to overcome the resistance
      are critical for their successful clinical development. EXPERIMENTAL DESIGN: We
      employed RS4;11 and MV4;11 cell lines, two acute leukemia models, to investigate
      acquired resistance mechanisms for both drugs in vitro and in vivo and evaluated
      several treatment regimens in xenograft mouse models to improve long-term,
      complete tumor regression. RESULTS: Resistance to either SAR405838 or ABT-263 (or
      its analogue ABT-737) develops in acute leukemia models in vitro and in vivo.
      RS4;11 and MV4;11 tumors treated with SAR405838 acquire resistance to the drug by
      mutation of the TP53 gene or compromise of p53 protein function. RS4;11 tumors
      treated with either ABT-263 or ABT-737 acquire resistance primarily through
      downregulation of BAX but not BAK. When acute leukemia cells become highly
      resistant to the MDM2 inhibitor, they retain their sensitivity to the Bcl-2
      inhibitors, or vice versa. Certain sequential or combination treatment of
      SAR405838 and ABT-263 can achieve longer-term tumor regression than treatment
      with either agent alone. CONCLUSIONS: Our study provides new insights into the
      mechanisms of acquired resistance of Bcl-2 and MDM2 inhibitors in acute leukemia
      models and suggests that certain sequential or combination treatment of these two
      distinct classes of apoptosis-inducing agents should be tested as new treatment
      strategies for acute leukemia in the clinic.

PMID- 25754351
TI  - Decline in faecal worm egg counts in lambs suckling ewes treated with lipophilic
      anthelmintics: implications for hastening development of anthelmintic resistance.
AB  - The aim for this experiment was to look for evidence of milk transfer of
      anthelmintic actives from ewes to their suckling lambs by reference to lambs'
      faecal worm egg count (WEC). The hypothesis was that WEC will decline in lambs
      suckling ewes treated with anthelmintics known to be lipophilic. One group of
      lactating Border Leicester*Merino ewes were treated (TX) with a combination of
      short (2.5mg/kg monepantel) and long-acting (1mg/kg moxidectin long-acting
      injection and a sustained release of 4.62g albendazole over 100 days)
      anthelmintics to remove gastrointestinal nematode (GIN) burden on day 0. The
      other group of lactating ewes (UTX) and all lambs (White Suffolk sires) were not
      treated. Ewes and lambs grazed as a single group and were exposed to GIN
      (predominately Haemonchus contortus) infection from pasture. Measurements were
      taken on days 0 and 7. WEC of lambs suckling UTX ewes increased from 6441 to
      10,341 eggs per gram (epg) between days 0 and 7, while there was a 51% reduction
      in WEC for lambs suckling TX ewes. Packed cell volume (PCV) was significantly
      higher for lambs suckling TX ewes on day 7 compared to lambs suckling UTX ewes
      (28.5% vs. 24.9%, p=0.039). These results suggest that lambs suckling ewes
      treated with lipophilic anthelmintics received a sub-therapeutic dose via milk
      which would increase selection within the GIN (H. contortus) population for
      anthelmintic resistance. 

PMID- 25754352
TI  - Trichinella spp. imported with live animals and meat.
AB  - Nematodes of the genus Trichinella are widely distributed throughout the world in
      omnivorous and carnivorous animals (mammals, birds, and reptiles) and in
      incidental hosts. To prevent the transmission of these zoonotic parasites to
      humans, meat samples from Trichinella spp. susceptible animals are tested at the
      slaughterhouse or in game processing plants. The aim of the present review was to
      collect documented cases on Trichinella infected animals, meat, or meat derived
      products which reached the international trade or were illegally introduced from
      one to another country in personal baggage. In the course of the last 60 years in
      the international literature, there have been 43 reports of importation of
      Trichinella spp. infected animals or meat, most of which (60%, 26/43) related to
      live horses or their meat. Meat or meat derived products from pigs, wild boar and
      bears, account only for 18.6% (8/43), 4.7% (3/43), and 14.3% (6/43),
      respectively. However, only live horses or their meat intended for human
      consumption, meat from a single wild boar, and live polar bears caught in the
      wild for zoos, were imported through the international market; whereas, meat from
      pigs, wild boars and bears were illegally introduced in a country in personal
      baggage. Trichinella infected animals or meat which were officially or illegally
      introduced in a country were the source of 3443 Trichinella infections in humans
      in a 40-year period (1975-2014). Most of these infections (96.8%) have been
      linked to horsemeat consumption, whereas meat from pigs, wild boars and bears
      accounted only for 2.2%, 0.7% and 0.3% of cases, respectively. This review shows
      the Trichinella spp. risk in the international animal and meat trade has been
      linked mainly to horses and only one time to wild boar, if they carcasses are not
      adequately tested, whereas pigs and other wild animals or their derived products
      infected with Trichinella spp. are unlikely to reach the international market by
      the official animal and meat trade. 

PMID- 25754353
TI  - Effect of structural changes of lignin during the autohydrolysis and organosolv
      pretreatment on Eucommia ulmoides Oliver for an effective enzymatic hydrolysis.
AB  - Eucommia ulmoides Oliver (EU) wood was successively treated by autohydrolysis and
      organosolv pretreatment integrated process. Autohydrolysis pretreatment
      facilitated xylooligosaccharides production, subsequent organosolv pretreatment
      to obtain high-purity lignin and digestible cellulose-rich residue. Results
      showed that the lignin fractions obtained exhibited smaller molecular weights,
      narrow polydispersity, more phenolic OH groups and higher syringyl/guaiacyl
      ratios (S/G) than the milled wood lignin. NMR characterization of the lignin
      revealed that the beta-O-4 linkages significantly cleaved and the structure of
      stilbene formed, but its resinol (beta-beta) was resistant to be degraded by
      organosolv delignification. Moreover, the glucose yield of the integrated residue
      achieved a maximum value of 89.3% after enzyme hydrolysis, separately about 1.0,
      1.3, 3.8 times as compared to that of the ethanol organosolv residue, the
      hydrothermally treated residue and the EU wood, respectively, which indicated
      that the integrated process was a promising approach to value-added utilization
      of the EU wood. 

PMID- 25754354
TI  - The effectiveness of excimer laser coronary atherectomy with contrast medium for
      underexpanded stent: The findings of optical frequency domain imaging.
AB  - Stent underexpansion is a risk factor for in-stent restenosis (ISR) and stent
      thrombosis. Although excimer laser coronary atherectomy (ELCA) with contrast
      medium was shown to be effective to improve stent underexpansion in undilatable
      lesions, precise mechanism of this technique was not well understood. We report a
      case of ISR with stent underoptimal implantation within a circumferential
      calcified atherosclerotic plaque beneath the stent strut that could not be
      dilated by repeated high-pressure balloon inflations. After rotational
      atherectomy, the mechanism of the underexpanded lesion could be obtained by
      optical frequency domain imaging (OFDI). High-pressure balloon could not dilate
      the underexpanded stent. Since ELCA with saline flush only gave intimal erosions
      and minor dissections, additional high-pressure balloon was also ineffective.
      Finally, ELCA with contrast medium could disrupt the calcific lesion beneath the
      underexpanded stent. The angiographic and OFDI findings confirmed the full stent
      expansion could be accomplished by further balloon dilatation with an ordinary
      pressure. ELCA with contrast medium is feasible to improve stent underexpansion
      by disrupting the calcified plaque behind the stent strut.

PMID- 25754355
TI  - Engineering Synergy: Energy and Mass Transport in Hybrid Nanomaterials.
AB  - An emerging class of materials that are hybrid in nature is propelling a
      technological revolution in energy, touching many fundamental aspects of energy
      generation, storage, and conservation. Hybrid materials combine classical
      inorganic and organic components to yield materials that manifest new
      functionalities unattainable in traditional composites or other related
      multicomponent materials, which have additive function only. This Research News
      article highlights the exciting materials design innovations that hybrid
      materials enable, with an eye toward energy-relevant applications involving
      charge, heat, and mass transport. 

PMID- 25754356
TI  - Use of clinical next-generation sequencing to identify melanomas harboring
      SMARCB1 mutations.
AB  - BACKGROUND: SMARCB1 (INI1/BAF47/SNF5) encodes a part of a multiprotein complex
      that regulates gene expression through chromatin remodeling. SMARCB1 expression
      is lost or downregulated in multiple human tumors, including epithelioid sarcoma,
      meningioma and rhabdoid tumors of the brain, soft tissue and kidney. METHODS: A
      46-gene or 50-gene next-generation sequencing AmpliSeq Cancer Panel (Life
      Technologies; San Francisco, CA, USA) was applied to ~1400 primary or metastatic
      melanoma tissues. RESULTS: We identified eight cases of melanoma harboring
      mutations in SMARCB1. Immunohistochemistry demonstrated preservation of SMARCB1
      protein expression in all cases. SMARCB1 mutations occurred together with TP53
      mutations in five of the eight cases, suggesting a functional relationship
      between these tumor suppressors in melanoma. CONCLUSIONS: Because single-base
      substitutions in SMARCB1 occur in a small subset of melanomas and do not affect
      SMARCB1 protein expression, such mutations would only be discovered by sequencing
      approaches. Our findings highlight the potential for next-generation sequencing
      platforms to identify mutations unexpected for melanoma that may contribute to
      its oncogenic potential. Though rare, the identification of SMARCB1 mutations
      adds to the growing literature regarding the role of epigenetic control
      mechanisms in melanoma progression and therapeutic resistance and provide a
      rationale for strategies targeting such alterations (via chromatin remodeling
      agents) in clinical trials.

PMID- 25754357
TI  - An Efficient and Cost-Effective Technique to Construct an Intraoral Central
      Bearing Tracing Device.
AB  - Intraoral central bearing tracing has been shown to be a predictable way of
      recording and verifying centric relation position for patients. Existing tracing
      devices are challenging to use due to several significant clinical limitations.
      In comparison to commercially available counterparts, this article presents a
      technique that simplifies instrumentation and clinical steps to make an intraoral
      tracer for making centric relation records, determining occlusal vertical
      dimension, and detecting deflective occlusal contacts in edentulous patients. 

PMID- 25754358
TI  - In defense of the passive voice in medical writing.
AB  - Few medical journals specifically instruct authors to use the active voice and
      avoid the passive voice, but advice to that effect is common in the large number
      of stylebooks and blogs aimed at medical and scientific writers. Such advice
      typically revolves around arguments that the passive voice is less clear, less
      direct, and less concise than the active voice, that it conceals the identity of
      the person(s) performing the action(s) described, that it obscures meaning, that
      it is pompous, and that the high rate of passive-voice usage in scientific
      writing is a result of conformity to an established and old-fashioned style of
      writing. Some of these arguments are valid with respect to specific examples of
      passive-voice misuse by some medical (and other) writers, but as arguments for
      avoiding passive-voice use in general, they are seriously flawed. In addition,
      many of the examples that stylebook writers give of inappropriate use are
      actually much more appropriate in certain contexts than the active-voice
      alternatives they provide. In this review, I examine the advice offered by anti
      passive writers, along with some of their examples of "inappropriate" use, and
      argue that the key factor in voice selection is sentence word order as determined
      by the natural tendency in English for the topic of discourse ("old" information)
      to take subject position and for "new" information to come later. Authors who
      submit to this natural tendency will not have to worry much about voice
      selection, because it will usually be automatic. 

PMID- 25754359
TI  - An April potpourri: mini focus issues, brief reports, podcasts, biomarkers,
      cognition, and more.

PMID- 25754360
TI  - Mobilizing clinical decision support to facilitate knowledge translation: a case
      study in China.
AB  - BACKGROUND: A wide gulf remains between knowledge and clinical practice. Clinical
      decision support has been demonstrated to be an effective knowledge tool that
      healthcare organizations can employ to deliver the "right knowledge to the right
      people in the right form at the right time". How to adopt various clinical
      decision support (CDS) systems efficiently to facilitate evidence-based practice
      is one challenge faced by knowledge translation research. METHOD: A computer
      aided knowledge translation method that mobilizes evidence-based decision
      supports is proposed. The foundation of the method is a knowledge representation
      model that is able to cover, coordinate and synergize various types of medical
      knowledge to achieve centralized and effective knowledge management. Next, web
      based knowledge-authoring and natural language processing based knowledge
      acquisition tools are designed to accelerate the transformation of the latest
      clinical evidence into computerized knowledge content. Finally, a batch of
      fundamental services, such as data acquisition and inference engine, are designed
      to actuate the acquired knowledge content. These services can be used as building
      blocks for various evidence-based decision support applications. RESULTS: Based
      on the above method, a computer-aided knowledge translation platform was
      constructed as a CDS infrastructure. Based on this platform, typical CDS
      applications were developed. A case study of drug use check demonstrates that the
      CDS intervention delivered by the platform has produced observable behavior
      changes (89.7% of alerted medical orders were revised by physicians). DISCUSSION:
      Computer-aided knowledge translation via a CDS infrastructure can be effective in
      facilitating knowledge translation in clinical settings.

PMID- 25754361
TI  - Evaluation of bile reflux in HIDA images based on fluid mechanics.
AB  - We propose a new method to help physicians assess, using a hepatobiliary
      iminodiacetic acid scan image, whether or not there is bile reflux into the
      stomach. The degree of bile reflux is an important index for clinical diagnosis
      of stomach diseases. The proposed method applies image-processing technology
      combined with a hydrodynamic model to determine the extent of bile reflux or
      whether the duodenum is also folded above the stomach. This condition in 2D
      dynamic images suggests that bile refluxes into the stomach, when endoscopy shows
      no bile reflux. In this study, we used optical flow to analyze images from Tc99m
      diisopropyl iminodiacetic acid cholescintigraphy (Tc99m-DISIDA) to ascertain the
      direction and velocity of bile passing through the pylorus. In clinical
      diagnoses, single photon emission computed tomography (SPECT) is the main
      clinical tool for evaluating functional images of hepatobiliary metabolism.
      Computed tomography (CT) shows anatomical images of the external contours of the
      stomach, liver, and biliary extent. By exploiting the functional fusion of the
      two kinds of medical image, physicians can obtain a more accurate diagnosis. We
      accordingly reconstructed 3D images from SPECT and CT to help physicians choose
      which cross sections to fuse with software and to help them more accurately
      diagnose the extent and quantity of bile reflux. 

PMID- 25754362
TI  - The Chlamydomonas heat stress response.
AB  - Heat waves occurring at increased frequency as a consequence of global warming
      jeopardize crop yield safety. One way to encounter this problem is to genetically
      engineer crop plants toward increased thermotolerance. To identify entry points
      for genetic engineering, a thorough understanding of how plant cells perceive
      heat stress and respond to it is required. Using the unicellular green alga
      Chlamydomonas reinhardtii as a model system to study the fundamental mechanisms
      of the plant heat stress response has several advantages. Most prominent among
      them is the suitability of Chlamydomonas for studying stress responses system
      wide and in a time-resolved manner under controlled conditions. Here we review
      current knowledge on how heat is sensed and signaled to trigger temporally and
      functionally grouped sub-responses termed response elements to prevent damage and
      to maintain cellular homeostasis in plant cells. 

PMID- 25754363
TI  - Persisting extreme acute corneal hydrops with a giant intrastromal cleft
      secondary to keratoconus.

PMID- 25754364
TI  - Photoacoustic imaging platforms for multimodal imaging.
AB  - Photoacoustic (PA) imaging is a hybrid biomedical imaging method that exploits
      both acoustical Epub ahead of print and optical properties and can provide both
      functional and structural information. Therefore, PA imaging can complement other
      imaging methods, such as ultrasound imaging, fluorescence imaging, optical
      coherence tomography, and multi-photon microscopy. This article reviews
      techniques that integrate PA with the above imaging methods and describes their
      applications. 

PMID- 25754365
TI  - The role of the acoustic radiation force in color Doppler twinkling artifacts.
AB  - PURPOSE: The aim of this experimental study was to evaluate whether the acoustic
      radiation force (ARF) is a potential source of twinkling artifacts in color
      Doppler images. METHODS: Color Doppler images were obtained using a clinical
      ultrasonic scanner (Voluson e, GE Healthcare) for a high contrast (+15 dB)
      circular scattering phantom at pulse repetition frequencies (PRFs) ranging from
      0.1 to 13 kHz. Ultrasound transmissions resulting in ARF were measured using a
      hydrophone at the various PRFs considered. The influence of ARF on the appearance
      of twinkling colors was examined via the common parameter PRF. This methodology
      is based on the fact that alternating positive and negative Doppler shifts
      induced by the ARF are centered at a PRF twice the maximum Doppler frequency on
      the color scale bar, whereas the twinkling color aliasing is expected to remain
      similar regardless of PRF. RESULTS: Color twinkling artifacts were observed to be
      most conspicuous at the lowest PRF of 0.1 kHz. The extent of twinkling rapidly
      decreased as the PRF increased, eventually disappearing when the PRF >=0.6 kHz.
      The measured ultrasound transmissions, however, were found to be insensitive to
      the PRF, and therefore it can be inferred that the PRF was insensitive to the
      ARF. CONCLUSION: Based on our experimental observations, the ARF may not be a
      source of color Doppler twinkling artifacts.

PMID- 25754366
TI  - Bedside ultrasound-guided percutaneous cystostomy in an infant in the neonatal
      intensive care unit.
AB  - We describe a case of an infant born at 39 weeks of gestation who was in the
      neonatal intensive care unit for postoperative management of congenital heart
      disease and underwent bedside ultrasound-guided percutaneous cystostomy to treat
      an iatrogenic urethral injury. The procedure was uneventful, successful, and no
      complications were noted. This case demonstrates that this procedure is safe and
      minimally invasive. Indications, contraindications, techniques, potential
      complications, and the safety of performing this procedure in a bedside setting
      are discussed. 

PMID- 25754367
TI  - Blood flow in intracranial aneurysms treated with Pipeline embolization devices:
      computational simulation and verification with Doppler ultrasonography on phantom
      models.
AB  - PURPOSE: The aim of this study was to validate a computational fluid dynamics
      (CFD) simulation of flow-diverter treatment through Doppler ultrasonography
      measurements in patient-specific models of intracranial bifurcation and side-wall
      aneurysms. METHODS: Computational and physical models of patient-specific
      bifurcation and sidewall aneurysms were constructed from computed tomography
      angiography with use of stereolithography, a three-dimensional printing
      technology. Flow dynamics parameters before and after flow-diverter treatment
      were measured with pulse-wave and color Doppler ultrasonography, and then
      compared with CFD simulations. RESULTS: CFD simulations showed drastic flow
      reduction after flow-diverter treatment in both aneurysms. The mean volume flow
      rate decreased by 90% and 85% for the bifurcation aneurysm and the side-wall
      aneurysm, respectively. Velocity contour plots from computer simulations before
      and after flow diversion closely resembled the patterns obtained by color Doppler
      ultrasonography. CONCLUSION: The CFD estimation of flow reduction in aneurysms
      treated with a flow-diverting stent was verified by Doppler ultrasonography in
      patient-specific phantom models of bifurcation and side-wall aneurysms. The
      combination of CFD and ultrasonography may constitute a feasible and reliable
      technique in studying the treatment of intracranial aneurysms with flow-diverting
      stents.

PMID- 25754368
TI  - A novel intracellular nitrogen-fixing symbiosis made by Ustilago maydis and
      Bacillus spp.
AB  - We observed that the maize pathogenic fungus Ustilago maydis grew in nitrogen (N)
      free media at a rate similar to that observed in media containing ammonium
      nitrate, suggesting that it was able to fix atmospheric N2 . Because only
      prokaryotic organisms have the capacity to reduce N2 , we entertained the
      possibility that U. maydis was associated with an intracellular bacterium. The
      presence of nitrogenase in the fungus was analyzed by acetylene reduction, and
      capacity to fix N2 by use of (15) N2 . Presence of an intracellular N2 -fixing
      bacterium was analyzed by PCR amplification of bacterial 16S rRNA and nifH genes,
      and by microscopic observations. Nitrogenase activity and (15) N incorporation
      into the cells proved that U. maydis fixed N2 . Light and electron microscopy,
      and fluorescence in situ hybridization (FISH) experiments revealed the presence
      of intracellular bacteria related to Bacillus pumilus, as evidenced by sequencing
      of the PCR-amplified fragments. These observations reveal for the first time the
      existence of an endosymbiotic N2 -fixing association involving a fungus and a
      bacterium.

PMID- 25754369
TI  - Initial experience using the rigid forceps technique to remove wall-embedded IVC
      filters.
AB  - INTRODUCTION: Severely tilted and embedded inferior vena cava (IVC) filters
      remain the most challenging IVC filters to remove. Heavy endothelialisation over
      the filter hook can prevent engagement with standard snare and cone recovery
      techniques. The rigid forceps technique offers a way to dissect the endothelial
      cap and reliably retrieve severely tilted and embedded filters. By developing
      this technique, failed IVC retrieval rates can be significantly reduced and the
      optimum safety profile offered by temporary filters can be achieved. We present
      our initial experience with the rigid forceps technique described by Stavropoulos
      et al. for removing wall-embedded IVC filters. METHODS: We retrospectively
      reviewed the medical imaging and patient records of all patients who underwent a
      rigid forceps filter removal over a 22-month period across two tertiary referral
      institutions. RESULTS: The rigid forceps technique had a success rate of 85%
      (11/13) for IVC filter removals. All filters in the series showed evidence of
      filter tilt and embedding of the filter hook into the IVC wall. Average filter
      tilt from the Z-axis was 19 degrees (range 8-56). Filters observed in the case
      study were either Bard G2X (n = 6) or Cook Celect (n = 7). Average filter dwell
      time was 421 days (range 47-1053). There were no major complications observed.
      CONCLUSION: The rigid forceps technique can be readily emulated and is a safe and
      effective technique to remove severely tilted and embedded IVC filters. The
      development of this technique across both institutions has increased the
      successful filter removal rate, with perceived benefits to the safety profile of
      our IVC filter programme.

PMID- 25754371
TI  - Disposable collection kit for rapid and reliable collection of saliva.
AB  - OBJECTIVES: To describe and evaluate disposable saliva collection kit for rapid,
      reliable, and reproducible collection of saliva samples. METHODS: The saliva
      collection kit comprised of a saliva absorbent swab and an extractor unit was
      used to retrieve whole saliva samples from 10 subjects. The accuracy and
      precision of the extracted volumes (3, 10, and 30 MUl) were compared to similar
      volumes drawn from control samples obtained by passive drool. Additionally, the
      impact of kit collection method on subsequent immunoassay results was verified by
      assessing salivary cortisol levels in the samples and comparing them to controls.
      RESULTS: The recovered volumes for the whole saliva samples were 3.85 +/- 0.28,
      10.79 +/- 0.95, and 31.18 +/- 1.72 MUl, respectively (CV = 8.76%) and 2.91 +/-
      0.19, 9.75 +/- 0.43, and 29.64 +/- 0.91 MUl, respectively, (CV = 6.36%) for the
      controls. There was a close correspondence between the salivary cortisol levels
      from the saliva samples obtained by the collection kit and the controls (R(2)  >
      0.96). CONCLUSIONS: The disposable saliva collection kit allows accurate and
      repeatable collection of fixed amounts of whole saliva and does not interfere
      with subsequent measurements of salivary cortisol. The simple collection process,
      lack of elaborate specimen recovery steps, and the short turnaround time (<3 min)
      should render the kit attractive to test subjects and researchers alike.

PMID- 25754372
TI  - What is the best approach in a patient with a failed aortic bioprosthetic valve:
      transcatheter aortic valve replacement or redo aortic valve replacement?
AB  - A best evidence topic in cardiac surgery was written according to a structured
      protocol. The question addressed was whether transcatheter aortic valve-in-valve
      replacement (viv-TAVR) or redo aortic valve replacement (rAVR) is the best
      strategy in a patient with a degenerative bioprosthetic aortic valve. Altogether,
      162 papers were found using the reported search, of which 12 represented the best
      evidence to answer the question. The authors, journal, date, country of
      publication, patient group, study type, outcomes and results of papers are
      tabulated. The results of the studies provided interesting results. All the
      studies are retrospective. Four papers reported the results of redo aortic valve
      replacement in patients with failed aortic bioprosthetic valve, six papers
      demonstrated their results with transcatheter aortic valve-in-valve replacement
      for the same indication and two papers reported their propensity-matched analysis
      of outcomes between viv-TAVR and rAVR in patients with previous cardiac surgery.
      Thirty-day mortality for rAVR was 2.3-15.5% and 0-17% for viv-TAVR. For rAVR,
      survival rate at 30 days was 83.6%, 76.1% at 1 year, 70.8% at 3 years, at 51.3
      66% at 5 years, 61% at 8 years and 61.5% at 10 years. For viv-TAVR, the overall
      Kaplan-Meier survival rate at 1 year was 83.2%. After viv-TAVR at 1 year, 86.2%
      of surviving patients were at New York Heart Association (NYHA) class I/II. The
      complications after rAVR were stroke (4.6-5.8%), reoperation for bleeding (6.9
      9.7%), low-cardiac output syndrome (9.9%) whereas complications after viv-TAVR at
      30 days were major stroke (1.7%), aortic regurgitation of at least moderate
      degree (25%), new permanent pacemaker implantation rate (0-11%), ostial coronary
      obstruction (2%), need for implantation of a second device (5.7%) and major
      vascular complications (9.2%). It is noteworthy to mention that there is a valve
      in-valve application that provides information to surgeons for choosing the
      correct size of the TAVR valve. Transcatheter aortic valve-in-valve procedures
      are clinically effective, at least in the short term, and could be an acceptable
      approach in selected high-risk patients with degenerative bioprosthetic valves.
      Redo AVR achieves acceptable medium and long-term results. Both techniques could
      be seen as complementary approaches for high-risk patients. 

PMID- 25754373
TI  - Do thymic malignancies respond to target therapies?
AB  - A best evidence topic in cardiothoracic surgery was written according to a
      structured protocol. The question addressed was 'Do thymic malignancies respond
      to target therapies?' Altogether, 347 papers were found using the reported
      search, of which, in our opinion, 16 papers represented the best evidence to
      answer the clinical question. The authors, journal, date and country of
      publication, patient group studied, study type, relevant outcomes and results of
      these papers were tabulated. We did not find any randomized controlled trials on
      target therapies for the thymic malignancies, due to the very small incidence of
      this tumour, and it seems unlikely that there will be any such trials in the
      foreseeable future. Three studies on target therapies showed that several cases
      of thymic malignancies were reported to have partial response (PR) to epidermal
      growth factor receptor tyrosine kinase inhibitors such as cetuximab and
      erlotinib, whereas, one study on erlotinib and another on gefitinib showed no
      activity. Proto-oncogene c-KIT (KIT) mutant thymic carcinomas were noted to
      benefit from target therapies, implying that systematic sequencing of KIT in
      thymic carcinoma tumours may be warranted for optimal patient selection. A study
      that investigated the efficacy of cixutumumab, a fully human IgG1 monoclonal
      antibody that binds to insulin-like growth factor 1 receptor, indicated that
      relapsed thymomas tended to respond, whereas thymic carcinoma did not. The
      antiangiogenesis agent belinostat had modest antitumour activity in heavily
      pretreated thymoma, but no response to thymic carcinoma was found. Several cases
      with metastatic thymic carcinoma showed that multitargeted kinase inhibitors,
      such as sunitinib and sorafenib, were effective. We concluded that, as the side
      effects of the agents were tolerable in almost all reported cases, target
      therapies can be an option for patients with heavily pretreated thymoma. 

PMID- 25754370
TI  - The Achilles' heel of senescent cells: from transcriptome to senolytic drugs.
AB  - The healthspan of mice is enhanced by killing senescent cells using a transgenic
      suicide gene. Achieving the same using small molecules would have a tremendous
      impact on quality of life and the burden of age-related chronic diseases. Here,
      we describe the rationale for identification and validation of a new class of
      drugs termed senolytics, which selectively kill senescent cells. By transcript
      analysis, we discovered increased expression of pro-survival networks in
      senescent cells, consistent with their established resistance to apoptosis. Using
      siRNA to silence expression of key nodes of this network, including ephrins
      (EFNB1 or 3), PI3Kdelta, p21, BCL-xL, or plasminogen-activated inhibitor-2,
      killed senescent cells, but not proliferating or quiescent, differentiated cells.
      Drugs targeting these same factors selectively killed senescent cells. Dasatinib
      eliminated senescent human fat cell progenitors, while quercetin was more
      effective against senescent human endothelial cells and mouse BM-MSCs. The
      combination of dasatinib and quercetin was effective in eliminating senescent
      MEFs. In vivo, this combination reduced senescent cell burden in chronologically
      aged, radiation-exposed, and progeroid Ercc1(-/Delta) mice. In old mice, cardiac
      function and carotid vascular reactivity were improved 5 days after a single
      dose. Following irradiation of one limb in mice, a single dose led to improved
      exercise capacity for at least 7 months following drug treatment. Periodic drug
      administration extended healthspan in Ercc1(-/?) mice, delaying age-related
      symptoms and pathology, osteoporosis, and loss of intervertebral disk
      proteoglycans. These results demonstrate the feasibility of selectively ablating
      senescent cells and the efficacy of senolytics for alleviating symptoms of
      frailty and extending healthspan.

PMID- 25754374
TI  - Cross-linguistic interactions influence reading development in bilinguals: a
      comparison between early balanced French-Basque and Spanish-Basque bilingual
      children.
AB  - This study investigates whether orthographic consistency and transparency of
      languages have an impact on the development of reading strategies and reading sub
      skills (i.e. phonemic awareness and visual attention span) in bilingual children.
      We evaluated 21 French (opaque)-Basque (transparent) bilingual children and 21
      Spanish (transparent)-Basque (transparent) bilingual children at Grade 2, and 16
      additional children of each group at Grade 5. All of them were assessed in their
      common language (i.e. Basque) on tasks measuring word and pseudoword reading,
      phonemic awareness and visual attention span skills. The Spanish speaking groups
      showed better Basque pseudoword reading and better phonemic awareness abilities
      than their French speaking peers, but only in the most difficult conditions of
      the tasks. However, on the visual attention span task, the French-Basque
      bilinguals showed the most efficient visual processing strategies to perform the
      task. Therefore, learning to read in an additional language affected differently
      Basque literacy skills, depending on whether this additional orthography was
      opaque (e.g. French) or transparent (e.g. Spanish). Moreover, we showed that the
      most noteworthy effects of Spanish and French orthographic transparency on Basque
      performance were related to the size of the phonological and visual grain used to
      perform the tasks. 

PMID- 25754375
TI  - Serum peptides as candidate biomarkers for dementia with Lewy bodies.
AB  - OBJECTIVE: For diagnosis of dementia with Lewy bodies (DLB), we tried to find
      blood biomarkers for the disease. METHODS: Serum peptides were comprehensively
      detected by mass spectrometry. Peptides of interest were identified by tandem
      mass spectrometry. RESULTS: One hundred forty-six peptides were detected in a
      training set consisting of 30 DLB patients, 30 patients with Alzheimer's disease
      (AD), and 28 healthy control (HC) subjects. Multivariate analysis for
      discriminating the DLB group from the non-DLB (AD and HC) group using ion
      intensity of four peptides (2898, 4052, 4090, and 5002 m/z) showed sensitivity of
      93.3% and specificity of 87.9% (DLB/nonDLB-4P model). In a testing set consisting
      of 20 DLB patients, 30 AD patients, and 14 HC subjects, this model showed
      sensitivity of 90.0% and specificity of 88.6%. DLB/nonDLB-4P model detected 86.7%
      and 90.0% of the AD patients as non-DLB in the training and testing sets,
      respectively, and discriminated all the 15 patients with amnestic mild cognitive
      impairment as non-DLB. Notably, a combination of two peptides (1737 and 5002 m/z)
      showed sensitivity of 95.0% and specificity of 93.3% for discriminating the DLB
      group from the AD group (DLB/nonDLB-2P model) in the testing set. The peptides
      used in these models included fragments from complement 4b, Wnt-2b, and
      lipopolysaccharide-binding protein, which were reported to be involved in the
      pathology of DLB or Parkinson's disease and hippocampal neurogenesis.
      CONCLUSIONS: Serum peptide profiles would provide useful DLB biomarker
      candidates, which may be implicated in the pathophysiology of the disease.

PMID- 25754376
TI  - Synthesis of oxazolidine-2,4-diones by a tandem phosphorus-mediated carboxylative
      condensation-cyclization reaction using atmospheric carbon dioxide.
AB  - The oxazolidine-2,4-dione motif is found frequently in biologically important
      compounds. A tandem phosphorus-mediated carboxylative condensation of primary
      amines and alpha-ketoesters/base-catalyzed cyclization reaction have been
      developed. These processes provide a novel and convenient access to various
      oxazolidine-2,4-diones in a one-pot fashion using atmospheric carbon dioxide and
      readily available substrates under very mild and transition-metal-free
      conditions. 

PMID- 25754377
TI  - Pregnant Women's Preferences for Men's Faces Differ Significantly from
      Nonpregnant Women.
AB  - INTRODUCTION: There is evidence that women's preferences for facial
      characteristics in men's faces change according to menstrual phase and sexual
      hormones. Literature indicates that the pregnancy is characterized by a specific
      sexual hormonal pattern with respect to all other physiological conditions
      concerning the sexual hormone status during the reproductive age, configuring
      this physiological condition as an excellent surrogate to study how the sexual
      hormones may affect many of the aspects concerning the sexual behavior. AIM: The
      aim of this study was to investigate pregnancy as a model of hormonal influence
      on women's facial preferences in short-term and long-term relationships and
      compare the choices of pregnant women with those of nonpregnant women. MAIN
      OUTCOME MEASURES: Measurement of women's preferences for synthetic men's faces,
      morphed from hyper-masculine to hypomasculine shape. MATERIALS AND METHODS: Forty
      six women in the third trimester of pregnancy, and 70 nonpregnant women took part
      in the study. All women were shown a composite male face. The sexual dimorphism
      of the images was enhanced or reduced in a continuous fashion using an open
      source morphing program that produced a sequence of 21 pictures of the same face
      warped from a feminized to a masculinized shape. RESULTS: Pregnant women's
      choices differed significantly from those of nonpregnant women. In fact, in the
      context of both a hypothetical short- (M = -0.4 +/- 0.11) and long-term
      relationship (M = -0.4 +/- 0.07) pregnant women showed a clear preference for a
      less masculine man's face than the other group (short-term: M = 0.15 +/- 0.13;
      long-term: M = -0.06 +/- 0.15; P < 0.0001). CONCLUSIONS: Women in the third
      trimester of pregnancy clearly prefer more feminine men's faces, distancing
      themselves from the choices of women in other physiological conditions concerning
      the sexual hormonal status during the reproductive age. However, other
      psychosocial variables may explain this interesting finding.

PMID- 25754378
TI  - Chemical composition of total flavonoids from Polygonum amplexicaule and their
      pro-apoptotic effect on hepatocellular carcinoma cells: Potential roles of
      suppressing STAT3 signaling.
AB  - Polygonum amplexicaule D. Don var. sinense Forb (P. amplexicaule) is a medical
      plant traditionally used in the treatment of malignant diseases including
      hepatocellular carcinoma (HCC), but the scientific basis underlying its anti-HCC
      activity remains poorly understood. Here, we explored the chemical profile of
      total flavonoids from P. amplexicaule (TFPA). Nine compounds that constituted the
      major components of TFPA were separated and identified. Further investigations
      revealed that TFPA dose-dependently induced HepG2, Huh-7 and H22 HCC cell
      apoptosis. In HCC cells, TFPA dramatically inhibited the transcriptional activity
      of signal transducer and activator of transcription 3 (STAT3). In addition, TFPA
      increased the expression of SHP-1, a protein tyrosine phosphatase catalyzing
      STAT3 dephosphorylation, in HCC cells. Animal studies showed that TFPA
      considerably provoked transplanted H22 cell apoptosis with undetectable
      toxicological effects on tumor-bearing mice. Consistently, TFPA dose-dependently
      inhibited transcriptional activity of STAT3 in transplanted tumor tissues. This
      study collectively demonstrated that TFPA has the capacity of inducing HCC cell
      apoptosis both in vitro and in vivo with low toxic effects on normal hepatocytes
      and vital organs of tumor-bearing mice. Suppressing STAT3 signaling is implicated
      in TFPA-mediated HCC cell apoptosis. 

PMID- 25754379
TI  - An in vitro study on the cytotoxicity of bismuth oxychloride nanosheets in human
      HaCaT keratinocytes.
AB  - As an emerging nanomaterial, bismuth oxychloride (BiOCl) has attracted explosive
      interests in diverse areas. However, how it interfaces with biological systems,
      particularly its interaction with human cells and the resulting effects are
      completely unknown. In this paper, the cytotoxicity of BiOCl nanosheets (NSs) was
      investigated toward a human skin derived cell line (HaCaT). It was found that
      BiOCl-NSs had no cytotoxicity at low concentrations (<0.5 ug/mL), whereas higher
      concentrations (5-100 ug/mL) of BiOCl-NSs could trigger toxic effects on HaCaT
      cells, with changes in cell morphology and impairment of intracellular structures
      (mitochondria and cytoskeleton). BiOCl-NSs also led to cell apoptosis and cells
      cycle arrest in G0/G1 phase. Flow cytometric data showed that BiOCl-NSs were
      effectively incorporated into HaCaT cells. Transmission electron microscope (TEM)
      images further revealed that BiOCl-NSs sequestered in the lysosomes,
      mitochondria, nuclei, and vesicles. Results of DCFH-DA assay and nutritional
      antioxidant N-acetylcysteine (NAC) experiments suggested that an oxidative stress
      mechanism was involved in the cytotoxic effects of BiOCl-NSs. Taken together,
      this work represents the first study on the behavior of BiOCl-NSs on human cells,
      and constitutes the first and essential step for the risk assessment of BiOCl
      nanomaterials. 

PMID- 25754380
TI  - Prospective analysis of outcomes and economic factors of same-day bilateral
      cataract surgery in the United States.
AB  - PURPOSE: To evaluate the visual and economic benefits of same-day bilateral
      cataract surgery versus separate-day bilateral cataract surgery in the United
      States. SETTING: Private practice, Amarillo, Texas, USA. DESIGN: Prospective
      controlled nonrandomized clinical trial. METHODS: A cohort of patients having
      same-day bilateral cataract surgery was age-matched with a cohort of control
      patients who had standard separate-day bilateral cataract surgery. The primary
      outcome was a comparison of the direct cost for the patient, physician,
      ambulatory surgery center (ASC), and third-party payer. RESULTS: The same-day
      cohort (42 patients, 84 eyes) had similar baseline characteristics and
      postoperative outcomes as the control cohort (42 patients, 84 eyes). The same-day
      cohort had less total distance traveled for care (P = .0039 and P < .0001 for in
      town and out-of-town residents, respectively), less total time spent traveling
      for care (P = .0008 and P < .0001 for in-town and out-of-town residents,
      respectively), less total number of visits required for care (P < .0001), and
      less total time for vision recovery (P < .0001) than the control cohort. The
      physician and ASC reimbursements were lower in the same-day cohort (P = .0028 and
      P = .0016, respectively), whereas the total physician time spent caring for the
      patient in surgery was not different between the 2 groups (P = .7310). The total
      ASC expenses were higher in the same-day cohort (P < .0001). The total third
      party payer cost was significantly less in the same-day cohort (P < .0001).
      CONCLUSION: Visual and economic benefits for the patient can be achieved with
      same-day bilateral cataract surgery in the U.S. at the present time. FINANCIAL
      DISCLOSURE: No author has a financial or proprietary interest in any material or
      method mentioned.

PMID- 25754381
TI  - Toric intraocular lens rotation to optimize refractive outcome despite
      appropriate intraoperative positioning.
AB  - We present 3 eyes of 2 patients who benefitted from toric intraocular lens (IOL)
      rotation despite appropriate intraoperative positioning. In each case,
      preoperative astigmatism measurements were obtained by manual keratometry,
      partial coherence interferometry, and corneal topography. In Case 1, a dramatic
      shift in corneal topography occurred after surgery, resulting in the need to
      rotate the toric IOL to maximize the refractive outcome. In Case 2 (both eyes),
      no significant change in topography occurred, but IOL rotation was required to
      maximize the refractive outcome despite appropriate IOL alignment based on
      preoperative measurements. Using an online toric IOL calculator, it was
      determined that rotation of the IOL would result in significantly improved
      astigmatic outcomes. At the final evaluation 2 months after IOL rotation, the
      residual manifest astigmatism was 0.50 diopter (D) in Case 1 and 0 D (right eye)
      and 0.75 D (left eye) in Case 2. Use of the toric IOL online calculator maximized
      the uncorrected visual and refractive outcomes. FINANCIAL DISCLOSURE: Neither
      author has a financial or proprietary interest in any material or method
      mentioned.

PMID- 25754382
TI  - The role of receptor for advanced glycation end products in airway inflammation
      in CF and CF related diabetes.
AB  - Cystic Fibrosis (CF) is often accompanied by diabetes leading to worsening lung
      function, the reason for which is unclear. The receptor for advanced-glycation
      end-products (RAGE) regulates immune responses and inflammation and has been
      linked to diabetes and possibly CF. We performed a pilot study to determine if CF
      and CF-related diabetes (CFRD) are associated with enhanced RAGE expression. Full
      length (fl)RAGE, soluble (s)RAGE, endogenous soluble (es)RAGE, S100A12 (enRAGE)
      and advanced-glycation-end-products (AGE) expression was assessed in serum, white
      blood cells and sputum of patients with CF; diabetes; CFRD and healthy subjects.
      Sputum enRAGE/sRAGE ratios were high in CF but particularly in CFRD which
      negatively correlated with % predicted FEV1. Serum AGE and AGE/sRAGE ratios were
      high in diabetics but not in CF. A complex, multifaceted approach was used to
      assess the role of RAGE and its ligands which is fundamental to determining their
      impact on airway inflammation. There is a clear association between RAGE activity
      in the airways of CF and CFRD patients that is not evident in the vascular
      compartment and correlates with lung function, in contrast to diabetes. This
      strongly suggests a role for RAGE in contributing to the inflammatory overdrive
      seen in CF and to a greater extent in CFRD. 

PMID- 25754383
TI  - Differences in sleep between black and white adults: an update and future
      directions.
AB  - Meta-analyses and other previous reviews have identified distinct ethnic/racial
      differences in the quantity, quality, and propensity for sleep disorders between
      black and white adults. The present article reviews the meta-analytic evidence
      along with recent epidemiological, community, and clinical studies to clarify
      what is known and not known about sleep differences between these two groups.
      Black individuals tend to have poorer sleep continuity and quality, excessively
      short or long sleep duration, greater sleep variability, and greater risk of
      sleep apnea than white individuals. The data suggest that these differences are
      attenuated yet persist in the face of several relevant confounders such as
      socioeconomic status, occupational factors, neighborhood context, and
      comorbidities. However, little is known about the mechanisms that explain ethnic
      disparities in sleep. We propose a conceptual model of potential mediators for
      future testing as well as other questions in need of investigation.

PMID- 25754384
TI  - Drug induced sleep endoscopy in the decision-making process of children with
      obstructive sleep apnea.
AB  - Tonsillectomy and adenoidectomy (T&A) is currently recommended in children with
      Obstructive Sleep Apnea (OSA). However, the condition persists after surgery in
      about one third of cases. It has been suggested that Drug Induced Sleep Endoscopy
      (DISE) may be of help for planning a more targeted and effective surgical
      treatment but evidence is yet weak. The aim of this review is to draw
      recommendation on the use of DISE in children with OSA. More specifically, we
      aimed at determine the proportion of cases whose treatment may be influenced by
      DISE findings. A comprehensive search of articles published from February 1983 to
      January 2014 listed in the PubMed/MEDLINE databases was performed. The search
      terms used were: "endoscopy" or "nasoendoscopy" or "DISE" and "obstructive sleep
      apnea" and "children" or "child" or "pediatric." The main outcome was the rate of
      naive children with hypertrophic tonsils and/or adenoids. The assumptions are
      that clinical diagnosis of hypertrophic tonsils and/or adenoids is reliable and
      does not require DISE, and that exclusive T&A may solve OSA in the vast majority
      of cases even in the presence of other concomitant sites of obstruction. Five
      studies were ultimately selected and all were case series. The median (range)
      number of studied children was 39 (15-82). Mean age varied from 3.2 to 7.8 years.
      The combined estimate rate of OSA consequent to hypertrophic tonsils and/or
      adenoids was 71% (95%CI: 64-77%). In children with Down Syndrome, the combined
      estimated rate of hypertrophic tonsils and/or adenoids was 62% (95%CI: 44-79%).
      Our findings show that DISE may be of benefit in a minority of children with OSA
      since up to two thirds of naive cases presents with hypertrophic tonsils and/or
      adenoids. Its use should be limited to those whose clinical evaluation is
      unremarkable or when OSA persists after T&A. 

PMID- 25754385
TI  - Sleep deprivation in adolescents: correlations with health complaints and health
      related quality of life.
AB  - OBJECTIVES: The present study aimed to evaluate the influences of sleep duration,
      sleep deprivation, and weekend variability of sleep upon other adolescents'
      features, namely those related to health and health-related quality of life.
      METHODS: The Health Behaviour in School-Aged Children (HBSC) survey is based on a
      self-completed questionnaire. The participants in the present study were 3476
      students (53.8% were girls) in the 8th and 10th grades at school; the mean age
      was 14.9 years (range 12.5-19.0). Subjective sleep duration during the weeknights
      and weekends was collected; sleep deprivation (SD) was considered whenever the
      difference was greater than 3 h. Health complaint frequency and health-related
      quality of life (with the Kidscreen 10) were collected. RESULTS: Sleep
      deprivation was present in 18.9% of the students. It was negatively correlated
      with sleep duration on weeknights. There were no gender differences, but SD
      increased with age and grade. Higher school grades were mainly associated with
      fatigue. A considerable number of adolescents had sleep problems (37.2%); 25.5%
      had difficulties in sleep initiation, which was more prevalent in adolescents
      with SD. The sleep duration on weeknights was decreased in the SD group. The
      average health-related quality of life was reduced in adolescents with SD. The
      frequency of health complaint was higher is adolescents with SD. Girls had
      significantly more health complaints than boys, with special focus on headaches.
      CONCLUSIONS: Sleep deprivation is associated with the perception of health
      related quality of life and perceived physical and mental health.

PMID- 25754387
TI  - Rapid surface enhanced Raman scattering detection method for chloramphenicol
      residues.
AB  - Chloramphenicol (CAP) is a widely used amide alcohol antibiotics, which has been
      banned from using in food producing animals in many countries. In this study,
      surface enhanced Raman scattering (SERS) coupled with gold colloidal
      nanoparticles was used for the rapid analysis of CAP. Density functional theory
      (DFT) calculations were conducted with Gaussian 03 at the B3LYP level using the 3
      21G(d) and 6-31G(d) basis sets to analyze the assignment of vibrations.
      Affirmatively, the theoretical Raman spectrum of CAP was in complete agreement
      with the experimental spectrum. They both exhibited three strong peaks
      characteristic of CAP at 1104 cm(-1), 1344 cm(-1), 1596 cm(-1), which were used
      for rapid qualitative analysis of CAP residues in food samples. The use of SERS
      as a method for the measurements of CAP was explored by comparing use of
      different solvents, gold colloidal nanoparticles concentration and absorption
      time. The method of the detection limit was determined as 0.1 MUg/mL using
      optimum conditions. The Raman peak at 1344 cm(-1) was used as the index for
      quantitative analysis of CAP in food samples, with a linear correlation of
      R(2)=0.9802. Quantitative analysis of CAP residues in foods revealed that the
      SERS technique with gold colloidal nanoparticles was sensitive and of a good
      stability and linear correlation, and suited for rapid analysis of CAP residue in
      a variety of food samples.

PMID- 25754388
TI  - 4-Mercaptophenylboronic acid: conformation, FT-IR, Raman, OH stretching and
      theoretical studies.
AB  - 4-Mercaptophenylboronic acid (4-mpba, C6H7BO2S) was investigated experimentally
      by vibrational spectroscopy. The molecular structure and spectroscopic parameters
      were studied by computational methods. The molecular dimer was investigated for
      intermolecular hydrogen bonding. Potential energy distribution analysis of normal
      modes was performed to identify characteristic frequencies. The present work
      provides a simple physical picture of the OH stretch vibrational spectra of 4
      mpba and analogues of the compound studied. When the different computational
      methods are compared, there is a strong evidence of the better performance of the
      BLYP functional than the popular B3LYP functional to describe hydrogen bonding in
      the dimer. The findings of this research work should be useful to
      experimentalists in their quests for functionalised 4-mpba derivatives. 

PMID- 25754389
TI  - Studies on the growth and characterization of a non linear optical crystal: 3
      Hydroxy Pyridinium Tartrate Mono Hydrate (3HPTMH).
AB  - Single crystals of 3 Hydroxy Pyridinium Tartrate Mono Hydrate (3HPTMH) was
      synthesised and successfully grown in mixed solvent of ethanol and water by slow
      evaporation technique at room temperature. 3HPTMH belongs to the orthorhombic
      crystal system with space group P212121. The lattice parameters of 3HPTMH are
      a=7.4597(2)A, b=8.7012(3)A, c=17.8786(5)A, V=1160.47(6)A(3), obtained by single
      crystal X ray diffraction studies. Hyperpolarizability and HOMO-LUMO analysis
      were performed for grown crystal using DFT calculations using Gaussian 03
      software. Functional groups were identified by FT-IR studies. The lower cut-off
      wavelength of the 3HPTMH has been identified by UV-Vis study. The thermal
      behavior has been studied by thermal gravimetric analysis and differential
      thermal analysis. The powder second harmonic generation efficiency of 3HPTMH was
      compared with KDP. 

PMID- 25754390
TI  - Ligand centered radical pathway in catechol oxidase activity with a trinuclear
      zinc-based model: synthesis, structural characterization and luminescence
      properties.
AB  - A new trinuclear zinc(II) complex, [Zn3(L)(NCS)2](NO3)2.CH3OH.H2O (1), of a (N,O)
      donor compartmental Schiff base ligand (H2L=N,N'-bis(3-methoxysalicylidene)-1,3
      diamino-2-propanol), has been synthesized in crystalline phase. The zinc(II)
      complex has been characterized by elemental analysis, IR spectroscopy, UV-Vis
      spectroscopy, powder X-ray diffraction study (PXRD), (1)H NMR, EI mass
      spectrometry and thermogravimetric analysis. PXRD revealed that 1 crystallizes in
      P-1 space group with a=9.218 A, b=10.849 A, c=18.339 A, with unit cell volume is
      2179.713(A)(3). Fluorescence spectra in methanolic solution reflect that
      intensity of emission for 1 is much higher compared to H2L and both the compounds
      exhibit good fluorescence properties. The complex 1 exhibits significant
      catalytic activities of biological relevance, viz. catechol oxidase. In methanol,
      it efficiently catalyzes the oxidation of 3,5-di-tert-butylcatechol (3,5-DTBC) to
      corresponding quinone via formation of a dinuclear species as [Zn2(L)(3,5-DTBC)].
      Electron Paramagnetic Resonance (EPR) experiment suggests generation of radicals
      in the presence of 3,5-DTBC and it may be proposed that the radical pathway is
      probably responsible for conversion of 3,5-DTBC to 3,5-DTBQ promoted by complex
      of redox-innocent Zn(II) ion.

PMID- 25754386
TI  - Partial vs radical nephrectomy for T1 renal tumours: an analysis from the British
      Association of Urological Surgeons Nephrectomy Audit.
AB  - OBJECTIVES: To analyse and compare data from the British Association of
      Urological Surgeons Nephrectomy Audit for perioperative outcomes of partial (PN)
      and radical nephrectomy (RN) for T1 renal tumours. PATIENTS AND METHODS: UK
      consultants were invited to submit data on all patients undergoing nephrectomy
      between 1 January and 31 December 2012 to a nationally established database using
      a standard pro forma. Analysis was made on patient demographics, operative
      technique, and perioperative data/outcome between PN and RN for T1 tumours.
      RESULTS: Overall, data from 6 042 nephrectomies were reported of which 1 768 were
      performed for T1 renal tumours. Of these, 1 082 (61.2%) were RNs and 686 (38.8%)
      were PNs. The mean age of patients undergoing PN was lower (PN 59 years vs RN 64
      years; P < 0.001) and so was the WHO performance score (PN 0.4 vs RN 0.7; P <
      0.001). PN for the treatment of T1a tumours (<=4 cm) accounted for 55.6% of
      procedures, of which 43.9% were performed using a minimally invasive technique.
      For T1b tumours (4-7 cm), 18.9% of patients underwent PN, in 33.3% of which a
      minimally invasive technique was adopted. The vast majority of RNs for T1 tumours
      were performed using a minimally invasive technique (90.3%). Of the laparoscopic
      PNs, 30.5% were robot-assisted. There was no significant difference in overall
      intraoperative complications between the RN and PN groups (4% vs 4.3%; P = 0.79).
      However, PN accounted for a higher overall postoperative complications rate (RN
      11.3% vs PN 17.6%; P < 0.001). RN was associated with a markedly reduced risk of
      severe surgical complications (Clavien Dindo classification grade >=3) compared
      with PN even after adjusting for technique (odds ratio 0.30; P = 0.002).
      Operation time between RN and PN was comparable (141 vs 145 min; P = 0.25). Blood
      loss was less in the RN group (mean for RN 165 vs PN 323 mL; P < 0.001); however,
      transfusion rates were similar (3.2% vs 2.6%; P = 0.47). RN was associated with a
      shorter length of stay (median 4 vs 5 days; P < 0.001). A direct comparison
      between robot-assisted and laparoscopic PN showed no significant differences in
      operation time, blood loss, warm ischaemia time, and intraoperative and
      postoperative complications. CONCLUSIONS: PN was the method of choice for
      treatment of T1a tumours whereas RN was preferred for T1b tumours. Minimally
      invasive techniques have been widely adopted for RN but not for PN. Despite the
      advances in surgical technique, a substantial risk of postoperative complications
      remains with PN.

PMID- 25754391
TI  - Theoretical and experimental study of the vibrational spectra of (para)symplesite
      and hornesite.
AB  - Arsenate water-bearing minerals, hornesite (Alsar, Macedonia) and symplesite
      (Laubach, Germany), were studied by vibrational (IR and Raman) spectroscopy and X
      ray powder diffraction. The observed vibrational spectra in both the high (1100
      600 cm(-1)) and low (600-450 cm(-1)) wavenumber regions of AsO4 and H2O
      vibrations could be used to discriminate the two studied minerals. Spectral
      differences are especially pronounced in the bending and stretching regions of
      the H2O vibrations in the IR spectra. The observed bands in IR and Raman spectra
      were tentatively assigned. To support the assignment, IR spectra were
      theoretically simulated. These calculations were performed using the crystal
      structure of parasymplesite (no structural information of symplesite has been
      published so far) and hornesite using a 3D periodic plane-wave pseudopotential
      density functional theory approach applying various combinations of exchange
      correlation functionals. In this article, we report on the first experimental
      study of the vibrational spectra of the very rare symplesite mineral.

PMID- 25754392
TI  - Studies on interaction of norbixin with DNA: multispectroscopic and in silico
      analysis.
AB  - The interaction of food colorant norbixin with calf thymus DNA (CTDNA) was
      investigated through UV-Visible spectroscopy, Fourier Transform Infrared (FTIR),
      Circular Dichroism (CD), Nuclear Magnetic Resonance (NMR), DNA melting studies,
      electrophoretic analysis, histological staining technique and molecular docking
      studies. The results indicated that norbixin interacted with CTDNA by partial
      intercalation mode. The binding constant (K) of norbixin with CTDNA was
      calculated to be 5.08*10(5) Mol(-1) L. FTIR and CD studies were coupled with (1)H
      NMR spectra revealed that norbixin intercalates partially and binds to the
      groove's, phosphate group, deoxyribose sugar of DNA and also induces
      conformational transition of B-form to A-form DNA. Agarose gel electrophoretic
      and histological staining technique results further prove that, norbixin
      specifically binds to the DNA in the cell. Moreover, molecular docking studies on
      the specific binding of norbixin with CTDNA have exhibited lowest conformation
      energy score of -3.2. Therefore, this food colorant has the ability to interact
      with DNA and it could emerge as a promising class of natural DNA targeted
      therapeutic.

PMID- 25754393
TI  - Silver nanoparticles enhanced flow injection chemiluminescence determination of
      gatifloxacin in pharmaceutical formulation and spiked urine sample.
AB  - Silver nanoparticles have been utilized for the enhanced chemiluminogenic
      estimation of fluoroquinolone antibiotic gatifloxacin. It has been found that the
      weak chemiluminescence intensity produced from the reaction between calcein and
      KMnO4 can further be strengthened by the addition of silver nanoparticles in the
      presence of gatifloxacin. This phenomenon has been exploited to the quantitative
      determination of gatifloxacin. Under the optimum experimental conditions, the
      calibration curves are linear over the range of 8.9*10(-9)-4.0*10(-6) M, while
      the limits of detections were found to be 2.6*10(-9) M with correlation
      coefficient value (r(2)) 0.9999. The relative standard deviation calculated from
      six replicate measurements (1.0*10(-4) M gatifloxacin) was 1.70%. The method was
      applied to pharmaceutical preparations and the results obtained were in
      reasonable agreement with the amount labeled on the formulations. The proposed
      method was also used for the determination of gatifloxacin in spiked urine
      samples with satisfactory results. No interference effects from some common
      excipients used in pharmaceutical preparations have been found.

PMID- 25754394
TI  - Structural, spectral, NLO and MEP analysis of the [MgO2Ti2(OPr(i)ii)6],
      [MgO2Ti2(OPr(i)i)2(acac)4] and [MgO2Ti2(OPr(i)i)2(bzac)4] by DFT method.
AB  - Quantum chemical calculations are performed on [MgO2Ti2(OPr(i))6] and
      [MgO2Ti2(OPr(i))2(L)4] complexes. L is acetylacetonate (acac) and
      benzoylacetonate (bzac) anion. The crystal structures of these complexes have not
      been obtained as experimentally but optimized structures of these complexes are
      obtained as theoretically in this study. Universal force field (UFF) and
      DFT/B3LYP method are used to obtain optimized structures. Theoretical spectral
      analysis (IR, (1)H and (13)C NMR) is compared with their experimental values. A
      good agreement is found between experimental and theoretical spectral analysis.
      These results mean that the optimized structures of mentioned complexes are
      appropriate. Additionally, the active sites of mentioned complexes are determined
      by molecular electrostatic potential (MEP) diagrams and non-linear optical (NLO)
      properties are investigated. 

PMID- 25754395
TI  - Interaction of sulfanilamide and sulfamethoxazole with bovine serum albumin and
      adenine: spectroscopic and molecular docking investigations.
AB  - Interaction between sulfanilamide (SAM) and sulfamethoxazole (SMO) with BSA and
      DNA base (adenine) was investigated by UV-visible, fluorescence, cyclic
      voltammetry and molecular docking studies. Stern-Volmer fluorescence quenching
      constant (Ka) suggests SMO is more quenched with BSA/adenine than that of SAM.
      The distance r between donor (BSA/adenine) and acceptor (SAM and SMO) was
      obtained according to fluorescence resonance energy transfer (FRET). The results
      showed that hydrophobic forces, electrostatic interactions, and hydrogen bonds
      played vital roles in the SAM and SMO with BSA/adenine binding interaction.
      During the interaction, sulfa drugs could insert into the hydrophobic pocket,
      where the non-radioactive energy transfer from BSA/adenine to sulfa drugs
      occurred with high possibility. Cyclic voltammetry results suggested that when
      the drug concentration is increased, the anodic electrode potential deceased. The
      docking method indicates aniline group is interacted with the BSA molecules. 

PMID- 25754396
TI  - Dose-ranging efficacy and safety study of ertugliflozin, a sodium-glucose co
      transporter 2 inhibitor, in patients with type 2 diabetes on a background of
      metformin.
AB  - AIM: To investigate the efficacy and safety of ertugliflozin, in a phase II dose
      ranging study, in patients with type 2 diabetes mellitus (T2DM) inadequately
      controlled on metformin. METHODS: A total of 328 patients [mean T2DM duration,
      6.3 years; mean glycated haemoglobin (HbA1c), 8.1%] were randomized to once-daily
      ertugliflozin (1, 5, 10, 25 mg), sitagliptin (100 mg) or placebo, for 12 weeks.
      The primary efficacy endpoint was change from baseline to week 12 in HbA1c
      concentration and the secondary efficacy endpoints were changes from baseline to
      week 12 in body weight, fasting plasma glucose (FPG) and systolic/diastolic blood
      pressure (SBP/DBP). Safety and tolerability were also monitored. RESULTS:
      Ertugliflozin (1-25 mg/day) produced significant reductions in HbA1c
      concentration [placebo-corrected least-squares mean (LSM) -0.45% (1 mg) to -0.72%
      (25 mg); p <= 0.002, similar to sitagliptin (-0.76%; p = 0.0001)], FPG (LSM -1.17
      to -1.90 mmol/l; p < 0.0001) and body weight (-1.15 to -2.15%; p < 0.0001). The
      LSM SBP decreased by -3.4 to -4.0 mmHg from baseline with ertugliflozin 5-25
      mg/day. No reductions in body weight or blood pressure were observed with
      sitagliptin. After randomization, 2.7% of patients (9/328) withdrew because of
      adverse events (AEs); the frequency of AEs was evenly distributed across groups.
      No dose-related increase in AE frequency occurred with ertugliflozin.
      Hypoglycaemia was reported in 5 (1.5%) randomized participants (all in the
      ertugliflozin group). The frequency of urinary tract infection was 3.2% for
      ertugliflozin (pooled across groups), 1.8% for sitagliptin, 7.4% for placebo, and
      the frequency of genital fungal infections was 3.7% for ertugliflozin (pooled)
      versus 1.9% for placebo. CONCLUSION: Ertugliflozin (1-25 mg/day) improved
      glycaemic control, body weight and blood pressure in patients with T2DM
      suboptimally controlled on metformin, and was well tolerated.

PMID- 25754397
TI  - Risk factors of early proximal gastric carcinoma in Chinese diagnosed using WHO
      criteria.
AB  - OBJECTIVE: The incidence of proximal gastric carcinoma (PGC) is rising worldwide
      for unknown reasons. Herein we compare the risk factors of early PGC with distal
      gastric carcinoma (DGC) in patients treated at a single tertiary hospital in
      China. METHODS: Risk factors of 379 consecutive surgically resected early gastric
      carcinoma (EGC) diagnosed according to the 2010 World Health Organization
      criteria were studied by reviewing their medical records and
      esophagogastroduodenoscopy/biopsy findings and interviewing patients and family
      members for the patients' history of environmental toxin exposure (ETE), dietary
      habits, family (FCH) and personal cancer history (PCH) and survival. Differences
      between PGC (n = 115), DGC (n = 264) and age-matched and gender-matched controls
      (n = 225) were compared. RESULTS: Proportion of early PGC in all EGC patients was
      increased significantly (P < 0.05). The independent risk factors for both PGC and
      DGC identified by multivariate analysis were intake of preserved food and little
      fruit, and gastric mucosal intestinal metaplasia and atrophy (all P < 0.05).
      Advanced age (odds ratio [OR] 9.83, P < 0.01), PCH (OR 5.09, P < 0.05), a high
      body mass index (>24 kg/m(2) ) (OR 2.79, P < 0.01) and ETE (OR 2.31, P < 0.05)
      were independent risk factors for PGC, but not male gender, tobacco or alcohol
      abuse, hiatus hernia, gastroesophageal reflux disease or columnar-lined
      esophagus. In contrast, FCH (OR 2.34, P < 0.01) and Helicobacter pylori infection
      (OR 2.81, P < 0.001) were independent risk factors for DGC. CONCLUSION:
      Independent risk factors for PGC in Chinese patients differ from those of DGC or
      esophageal adenocarcinoma, supporting the classification of PGC as a separate
      gastric carcinoma entity in the Chinese populations.

PMID- 25754398
TI  - Spatio-temporal response properties of local field potentials in the primate
      superior colliculus.
AB  - Local field potentials (LFPs) are becoming increasingly popular in
      neurophysiological studies. However, to date, most of the knowledge about LFPs
      has been obtained from cortical recordings. Here, we recorded single unit
      activity (SUA) and LFPs simultaneously from the superior colliculus (SC) of
      behaving rhesus monkeys. The SC is a midbrain structure that plays a central role
      in the visual orienting response. Previous studies have characterised the visual
      and visuomotor response properties of SUA in the superficial layers of the SC and
      the intermediate layers of the SC, respectively. We found that the signal
      properties of SUA were well preserved in the LFPs recorded from the SC. The SUA
      and LFPs had similar spatial and temporal properties, and the response properties
      of LFPs differed across layers, i.e. purely visual in the superficial layers of
      the SC but showing significant motor responses in the intermediate layers of the
      SC. There were also differences between SUA and LFPs. LFPs showed a significant
      reversal of activity following the phasic visual response, suggesting that the
      neighboring neurons were suppressed. The results indicate that the LFP can be
      used as a reliable measure of the SC activity in lieu of SUA, and open up a new
      way to assess sensorimotor processing within the SC. 

PMID- 25754399
TI  - Unintentional and efficient relational priming.
AB  - If relational priming is responsible for unintentional analogical reasoning, as
      has been suggested, it too should occur unintentionally. However, results from
      previous studies are inconclusive - studies that use the sensicality task usually
      demonstrate unintentional priming, while lexical decision tasks have failed to
      capture the effect without explicitly instructing participants to note and use
      the relational similarity in the stimuli. We discuss possible reasons for these
      contradictory results. Based on this discussion, we aimed to maximize our chances
      to find an effect by ensuring that the primes and targets elicit the same
      processing, by using a longer SOA, suitable for the more complex nature of the
      task, and by ensuring that the stimuli are good exemplars of the relations that
      hold between them. We present two experiments that obtained unintentional and
      efficient priming of relations with a lexical decision task. Participants made a
      lexical decision for a target pair of words more quickly when it was preceded by
      a similarly related pair of words, compared to an unrelated pair. Participants
      were not instructed to note and use the relations. Experiment 2 extended those
      results by showing that the effect is present even when executive working memory
      resources are occupied by a secondary task. Even though it turned out that the
      base pairs differed on semantic similarity, co-occurrence and imageability
      between the two conditions, these differences were not responsible for the
      effect. Thus, relations can be primed unintentionally and efficiently, even when
      relational integration is not necessitated by task demands.

PMID- 25754400
TI  - Family Care of People with Intellectual Disability in Rural China: A Magnified
      Responsibility.
AB  - BACKGROUND: Welfare for the disabled is becoming an important issue in China and
      care for people with intellectual disability is challenging because of the
      inadequacies in formal support and the social service system. MATERIAL AND
      METHOD: Based on ethnographic research in two villages in North China, this paper
      analyses the dilemmas of family care for people with intellectual disability. The
      essential data is the ethnographic record of three cases. RESULTS: Rural families
      strive to provide care through a set of arrangements and bear tremendous stress
      in the process. CONCLUSION: Family care for people with intellectual disability
      in rural China has been increasingly challenged by the forces of labour
      migration, demographic changes and the ever-growing processes of commoditization.
      The role of the state has to be strengthened in welfare provision to balance the
      weakened family care ethos in transforming societies.

PMID- 25754401
TI  - A case of mistaken identity: unilateral erythema elevatum diutinum associated
      with IgA paraproteinaemia.
AB  - We report the case of a 27-year-old woman presenting with unilateral painless
      nodules of the left hand following trauma. Initially diagnosed as nontuberculous
      mycobacterium infection and treated with prolonged courses of antibiotics with
      little improvement, the condition was subsequently diagnosed histologically as
      erythema elevatum diutinum (EED). The lesion was treated with surgical excision,
      and the patient remained lesion-free at the 1-year follow-up. Although the lesion
      was otherwise asymptomatic, further investigation demonstrated an underlying IgA
      paraproteinaemia. This case should alert physicians to consider the diagnosis of
      EED in a unilateral presentation, and highlights the importance of investigation
      for underlying associated haematological disease. 

PMID- 25754402
TI  - How can we promote smoking cessation in people with schizophrenia in practice? A
      clinical overview.
AB  - OBJECTIVE: High rates of smoking and nicotine dependence are associated with
      increased physical comorbidity and premature death in people with schizophrenia.
      We conducted a clinical overview to establish how smoking cessation should be
      promoted in practice. METHOD: Systematic clinical review of major electronic
      databases from inception till November 2014. RESULTS: A growing body of evidence
      supports pharmacological interventions to assist smoking cessation. The most
      promising evidence is for bupropion with several meta-analyses demonstrating its
      effectiveness. Currently, there is limited evidence demonstrating the
      effectiveness of nicotine replacement therapy (NRT) and varenicline, although
      this is likely to be due to the paucity of research. There are no consistent data
      to suggest that pharmacological interventions increase adverse events.
      Behavioural and psychosocial interventions also demonstrate promise, particularly
      when combined with pharmacotherapy. Careful monitoring of antipsychotic levels
      (in particular clozapine) is essential, and the promotion of physical activity
      may be useful to negate potential weight gain and diabetes risk following smoking
      cessation. CONCLUSION: Evidence from systematic reviews and meta-analyses
      suggests that smoking cessation interventions are effective in people with
      schizophrenia, although more long-term research is required. Promoting smoking
      cessation should be given utmost priority in clinical practice, and we offer
      practical strategies to facilitate this.

PMID- 25754403
TI  - Thyroidectomy using pure natural orifice transluminal endoscopic surgery in a
      porcine model.
AB  - Surgical procedures for thyroid disease that provide cosmetically acceptable
      results are in demand. Natural orifice transluminal endoscopic surgery (NOTES) is
      performed through natural orifices and thus avoids incision of the body wall.
      This study aimed to develop an incision-free surgical procedure for thyroid
      lobectomy using pure NOTES with an oral approach. In six pig carcasses, an
      incision was made between the mandible and subcutaneous tissue under direct
      vision. After subcutaneous dissection and identification of the hyoid bone, the
      operative field was developed under endoscopic view. After the thyrohyoid
      membrane was identified, dissection was continued along the thyroid cartilage
      until the cricoid cartilage was identified and the thyroid isthmus was reached.
      An original retractor was inserted between dissected tissues to lift and fix the
      carcass. The thyroid gland was successfully removed through the incision. Similar
      macroscopic and histological findings were observed on the normal and treated
      sides, with no damage to the recurrent laryngeal nerves. The times required for
      securing the operative field and thyroidectomy improved with each operation. This
      study suggests the feasibility and safety of using pure NOTES for thyroidectomy
      through a subcutaneous route with an original retractor. 

PMID- 25754404
TI  - Unravelling rootstock*scion interactions to improve food security.
AB  - While much recent science has focused on understanding and exploiting root traits
      as new opportunities for crop improvement, the use of rootstocks has enhanced
      productivity of woody perennial crops for centuries. Grafting of vegetable crops
      has developed very quickly in the last 50 years, mainly to induce shoot vigour
      and to overcome soil-borne diseases in solanaceous and cucurbitaceous crops. In
      most cases, such progress has largely been due to empirical interactions between
      farmers, gardeners, and botanists, with limited insights into the underlying
      physiological mechanisms. Only during the last 20 years has science realized the
      potential of this old activity and studied the physiological and molecular
      mechanisms involved in rootstock*scion interactions, thereby not only explaining
      old phenomena but also developing new tools for crop improvement. Rootstocks can
      contribute to food security by: (i) increasing the yield potential of elite
      varieties; (ii) closing the yield gap under suboptimal growing conditions; (iii)
      decreasing the amount of chemical (pesticides and fertilizers) contaminants in
      the soil; (iv) increasing the efficiency of use of natural (water and soil)
      resources; (v) generating new useful genotypic variability (via epigenetics); and
      (vi) creating new products with improved quality. The potential of grafting is as
      broad as the genetic variability able to cross a potential incompatibility
      barrier between the rootstock and the scion. Therefore, understanding the
      mechanisms underlying the phenotypic variability resulting from
      rootstock*scion*environment interactions will certainly contribute to developing
      and exploiting rootstocks for food security. 

PMID- 25754406
TI  - Phytosulfokine peptide signalling.
AB  - Phytosulfokine (PSK) belongs to the group of plant peptide growth factors. It is
      a disulfated pentapeptide encoded by precursor genes that are ubiquitously
      present in higher plants, suggestive of universal functions. Processing of the
      preproprotein involves sulfonylation by a tyrosylprotein sulfotransferase in the
      trans-golgi and proteolytic cleavage in the apoplast. The secreted peptide is
      perceived at the cell surface by a membrane-bound receptor kinase of the leucine
      rich repeat family. The PSK receptor PSKR1 from Arabidopsis thaliana is an active
      kinase and has guanylate cyclase activity resulting in dual-signal outputs.
      Receptor activity is regulated by calmodulin. While PSK may be an autocrine
      growth factor, it also acts non-cell autonomously by promoting growth of cells
      that are receptor-deficient. In planta, PSK has multiple functions. It promotes
      cell growth, acts in the quiescent centre cells of the root apical meristem,
      contributes to funicular pollen tube guidance, and differentially alters immune
      responses depending on the pathogen. It has been suggested that PSK integrates
      growth and defence signals to balance the competing metabolic costs of these
      responses. This review summarizes our current understanding of PSK synthesis,
      signalling, and activity. 

PMID- 25754405
TI  - Aequorin-based luminescence imaging reveals differential calcium signalling
      responses to salt and reactive oxygen species in rice roots.
AB  - It is well established that both salt and reactive oxygen species (ROS) stresses
      are able to increase the concentration of cytosolic free Ca(2+) ([Ca(2+)]i),
      which is caused by the flux of calcium (Ca(2+)). However, the differences between
      these two processes are largely unknown. Here, we introduced recombinant aequorin
      into rice (Oryza sativa) and examined the change in [Ca(2+)]i in response to salt
      and ROS stresses. The transgenic rice harbouring aequorin showed strong
      luminescence in roots when treated with exogenous Ca(2+). Considering the
      histological differences in roots between rice and Arabidopsis, we reappraised
      the discharging solution, and suggested that the percentage of ethanol should be
      25%. Different concentrations of NaCl induced immediate [Ca(2+)]i spikes with the
      same durations and phases. In contrast, H2O2 induced delayed [Ca(2+)]i spikes
      with different peaks according to the concentrations of H2O2. According to the
      Ca(2+) inhibitor research, we also showed that the sources of Ca(2+) induced by
      NaCl and H2O2 are different. Furthermore, we evaluated the contribution of
      [Ca(2+)]i responses in the NaCl- and H2O2-induced gene expressions respectively,
      and present a Ca(2+)- and H2O2-mediated molecular signalling model for the
      initial response to NaCl in rice.

PMID- 25754407
TI  - Galpha13 mediates human cytomegalovirus-encoded chemokine receptor US28-induced
      cell death in melanoma.
AB  - US28, a constitutively active G-protein-coupled receptor encoded by the human
      cytomegalovirus, leads to mechanistically unknown programmed cell death. Here we
      show that expression of wild-type US28 in human melanoma cells leads to apoptotic
      cell death via caspase 3 activation along with reduced cell proliferation.
      Reduced tumor growth upon US28 expression was observed in a xenograft mouse
      model. The signaling mute US28R129A showed a reduced antiproliferative effect. On
      evaluating different G-proteins coupled to US28 for signal transduction, Galpha13
      was identified as the main G-protein executing the apoptotic effect. Silencing of
      Galpha13 but not Galphaq resulted in a substantial increase in cell survival.
      Overexpression of Galpha13 but not Galphaq and their GTPase deficient forms
      Galpha13Q226L and GalphaqQ209L, respectively, confirmed the requirement of
      Galpha13 for US28 mediated cell death. Increasing expression of Galpha13 alone
      induced cell death underscoring its relay function for US28 mediated decreased
      cell viability. Further reduced expression of Galpha13 in melanoma cell lines
      isolated from advanced lesions and melanoma tissue was observed. These findings
      identified Galpha13 as crucial for US28-induced cell death, substantiating that
      the effect of US28 on cell fate depends on preferred G-protein binding. 

PMID- 25754408
TI  - Characterization of HIV drug resistance mutations among patients failing first
      line antiretroviral therapy from a tertiary referral center in Lusaka, Zambia.
AB  - In settings of resource constraint, an understanding of HIV drug resistance can
      guide antiretroviral therapy (ART) at switch to second-line therapy. To determine
      the prevalence of such HIV drug resistance mutations (HIV DRM), we used an in
      house sequencing assay in the pol gene (protease and partial reverse
      transcriptase) in a cohort of patients suspected of failing a first-line regimen,
      which in Zambia comprises two nucleoside/nucleotide reverse transcriptase
      inhibitors (NRTIs) and one non-nucleoside reverse transcriptase inhibitor
      (NNRTI). Our analysis cohort (n = 68) was referred to the University Teaching
      Hospital in Lusaka from November 2009 to October 2012. Median duration on first
      line ART to suspected treatment failure was 3.2 years (IQR 1.7-4.7 years). The
      majority of patients (95%) harbored HIV-1 subtype C virus. Analysis of reverse
      transcriptase revealed M184V (88%), K103N/S (32%), and Y181C/I/V (41%) DRMs, with
      the latter conferring reduced susceptibility to the salvage therapy candidates
      etravirine and rilpivirine. Three patients (5%) had major protease inhibitor (PI)
      resistance mutations: all three had the V82A mutation, and one patient (Clade J
      virus) had a concurrent M46I, Q58E, and L76V DRM. HIV-1 genotyping revealed major
      and minor DRMs as well as high levels of polymorphisms in subtype C isolates from
      patients failing first-line antiretroviral therapy. Closer monitoring of DRM
      mutations at first-line failure can inform clinicians about future options for
      salvage therapy.

PMID- 25754409
TI  - [Surgical sepsis].
AB  - Sepsis represents a clinical syndrome following an infection and it is
      characterized by classical signs of systemic inflammatory response syndrome
      (SIRS): fever or ipothermia, tachycardia, tachipnea, leucocytosis or leucopenia.
      There may also be symptoms related to a specific infection such as a cough in
      pneumonia or burning with urination in a kidney infection, and abdominal pain in
      an intraabdominal sepsis. Common locations for the primary infection include
      lungs, brain, urinary tract, skin and soft tissues, and mainly abdominal organs.
      Patients who develop sepsis have an increased risk of complications and death and
      face higher healthcare costs and longer treatment. The infection is caused most
      commonly by bacteria, but can also be by fungi, viruses, or parasites. Severe
      sepsis is sepsis causing poor organ function or insufficient blood flow; septic
      shock is the situation with ipotension and/or need for high dosage of inotropes
      or vasopressors and multiple organ failure syndrome is when multiple organ
      dysfunction or failure is present. Outcomes depend on the severity of disease
      with the risk of death from sepsis being as high as 30%, severe sepsis as high as
      50%, and septic shock as high as 80%. Prevention, early diagnosis, and treatment,
      both medical (antibiotics) and surgical (source control), together with the
      prompt intensive care and organ support are crucial to increase survival rate. 

PMID- 25754410
TI  - [Ureterovaginal fistulae].
AB  - Ureterovaginal fistulae are pathological communications between the ureter and
      the vagina; it commonly occur as a rare but serious sequela of unrecognized
      distal ureteral injuries during pelvic operations. Patients may present symptoms
      as leakage of urine from the vagina, flank pain and fever; in some cases it could
      be possible also the loss of renal function. The purpose of this study is to
      review the articles from 1991 to 2014 to evaluate the most correct diagnostic
      procedures and endourological and surgical techniques used in the management of
      ureterovaginal fistula. Nowadays computered tomography and retrograde pielography
      are the most commonly diagnostic modalities used to identify fistulous tract and
      to describe its anatomical position. The major of ureterovaginal fistulae can be
      successfully managed by conservative methods. Modern endourological treatment
      will result in resolution of a ureterovaginal fistula if retrograde or
      anterograde passage of a suitable internal stent is feasible. When stenting
      failed or in complicated cases, ureteral reimplantation is necessary.
      Ureteroneocystostomy, psoas hitch and Boari flap are three different possible
      surgical techniques used to realized an ureteral reimplantation. Both open and
      mini invasive (laparoscopy and robot assisted) surgical approach have proved
      successful.

PMID- 25754411
TI  - Chemerin-induced mitochondrial dysfunction in skeletal muscle.
AB  - Chemerin is a novel adipocyte-derived factor that induces insulin resistance in
      skeletal muscle. However, the effect of chemerin on skeletal muscle mitochondrial
      function has received little attention. In the present study, we investigated
      whether mitochondrial dysfunction is involved in the pathogenesis of chemerin
      mediated insulin resistance. In this study, we used recombinant adenovirus to
      express murine chemerin in C57BL/6 mice. The mitochondrial function and structure
      were evaluated in isolated soleus muscles from mice. The oxidative mechanism of
      mitochondrial dysfunction in cultured C2C12 myotubes exposed to recombinant
      chemerin was analysed by western blotting, immunofluorescence and quantitative
      real-time polymerase chain reaction. The overexpression of chemerin in mice
      reduced the muscle mitochondrial content and increased mitochondrial autophagy,
      as determined by the increased conversion of LC3-I to LC3-II and higher
      expression levels of Beclin1 and autophagy-related protein-5 and 7. The chemerin
      treatment of C2C12 myotubes increased the generation of mitochondrial reactive
      oxygen species, concomitant with a reduced mitochondrial membrane potential and
      increased the occurrence of mitochondrial protein carbonyls and mitochondrial DNA
      deletions. Knockdown of the expression of chemokine-like receptor 1 or the use of
      mitochondria-targeting antioxidant Mito-TEMPO restored the mitochondrial
      dysfunction induced by chemerin. Furthermore, chemerin exposure in C2C12 myotubes
      not only reduced the insulin-stimulated phosphorylation of protein kinase B (AKT)
      but also dephosphorylated forkhead box O3alpha (FoxO3alpha). Chemerin-induced
      mitochondrial autophagy likely through an AKT-FoxO3alpha-dependent signalling
      pathway. These findings provide direct evidence that chemerin may play an
      important role in regulating mitochondrial remodelling and function in skeletal
      muscle. 

PMID- 25754413
TI  - Colliding epidemics requires collaborating programmes.

PMID- 25754412
TI  - Disambiguating the optic nerve from the surrounding cerebrospinal fluid:
      Application to MS-related atrophy.
AB  - PURPOSE: Our goal is to develop an accurate, automated tool to characterize the
      optic nerve (ON) and cerebrospinal fluid (CSF) to better understand ON changes in
      disease. METHODS: Multi-atlas segmentation is used to localize the ON and sheath
      on T2-weighted MRI (0.6 mm(3) resolution). A sum of Gaussian distributions is fit
      to coronal slice-wise intensities to extract six descriptive parameters, and a
      regression forest is used to map the model space to radii. The model is validated
      for consistency using tenfold cross-validation and for accuracy using a high
      resolution (0.4 mm(2) reconstructed to 0.15 mm(2)) in vivo sequence. We evaluated
      this model on 6 controls and 6 patients with multiple sclerosis (MS) and a
      history of optic neuritis. RESULTS: In simulation, the model was found to have an
      explanatory R-squared for both ON and sheath radii greater than 0.95. The
      accuracy of the method was within the measurement error on the highest possible
      in vivo resolution. Comparing healthy controls and patients with MS, significant
      structural differences were found near the ON head and the chiasm, and structural
      trends agreed with the literature. CONCLUSION: This is a first demonstration that
      the ON can be exclusively, quantitatively measured and separated from the
      surrounding CSF using MRI.

PMID- 25754414
TI  - Comparison of thrice-daily premixed insulin (insulin lispro premix) with basal
      bolus (insulin glargine once-daily plus thrice-daily prandial insulin lispro)
      therapy in east Asian patients with type 2 diabetes insufficiently controlled
      with twice-daily premixed insulin: an open-label, randomised, controlled trial.
AB  - BACKGROUND: Unlike in western countries, premixed insulin is widely used as the
      starter insulin in Asian patients instead of basal insulin. The use of basal
      bolus therapy as an intensification regimen is not common in Asia despite poor
      glycaemic control after starting insulin therapy. An alternative insulin
      intensification regimen with a similar efficacy and safety profile to basal-bolus
      therapy, but of higher convenience, is urgently needed. The efficacy and safety
      of insulin lispro mix thrice-daily was compared with basal-bolus therapy in Asian
      patients with type 2 diabetes who were insufficiently controlled on twice-daily
      premixed insulin. METHODS: This open-label, randomised, active comparator
      controlled, parallel-group trial was done at 24 centres in China, Taiwan, and
      South Korea. Patients with type 2 diabetes who were inadequately controlled on
      twice-daily premixed insulin were randomly assigned (1:1) to receive either
      insulin lispro mix (mix 50 before breakfast and lunch plus mix 25 before dinner)
      or basal-bolus therapy (insulin glargine at bedtime plus prandial insulin lispro
      thrice-daily) for 24 weeks. Randomisation was done by a computer-generated random
      sequence and was stratified by country or region and baseline HbA1c. Treatment
      assignments were masked from the study team assessing outcomes but not from
      investigators and patients. The primary outcome was change from baseline in HbA1c
      at week 24 in all randomly assigned patients who received at least one dose of
      study drug. Analysis was by modified intention to treat, with the per-protocol
      population used as a supportive analysis. This study is registered with
      ClinicalTrials.gov, number NCT01175811. FINDINGS: Between Feb 7, 2011, and Nov 7,
      2012, 402 patients were enrolled (199 in the premix group, 203 in the basal-bolus
      group) and 399 were included in the primary analysis (197 in the premix group,
      202 in the basal-bolus group). HbA1c change at week 24 was -1.1% for both
      treatment groups. The least squares mean difference between groups in HbA1c
      change from baseline was 0% (95% CI -0.1 to 0.2). Insulin lispro mix was non
      inferior to basal-bolus therapy based on the prespecified margin of 0.4%. The
      frequency of adverse events, and the incidences and 30-day rates of nocturnal and
      overall hypoglycaemia were comparable between groups. No severe hypoglycaemia was
      reported. INTERPRETATION: A premixed insulin lispro regimen thrice-daily was non
      inferior to basal-bolus therapy in terms of overall glycaemic control and thus
      could be an option for intensified insulin regimen in Asian patients with type 2
      diabetes who are inadequately controlled with twice-daily premixed insulin.

PMID- 25754415
TI  - Effect of diabetes on tuberculosis control in 13 countries with high
      tuberculosis: a modelling study.
AB  - BACKGROUND: Diabetes increases the risk of tuberculosis incidence and the risk of
      adverse treatment outcomes in patients with tuberculosis. Because prevalence of
      diabetes is increasing in low-income and middle-income countries where the burden
      of tuberculosis is high, prevention of diabetes carries the potential to improve
      tuberculosis control worldwide. METHODS: We used dynamic tuberculosis
      transmission models to analyse the potential effect of diabetes on tuberculosis
      epidemiology in 13 countries with high tuberculosis burden. We used data for
      previous diabetes prevalence in each country and constructed scenarios to
      represent the potential ranges of future diabetes prevalence. The country
      specific model was calibrated to the estimated trend of tuberculosis incidence.
      We estimated the tuberculosis burden that can be reduced by alternative scenarios
      of diabetes prevention. FINDINGS: If the prevalence of diabetes continues to rise
      as it has been in the past decade in the 13 countries (base case scenario), by
      2035, the cumulative reduction in tuberculosis incidence would be 8.8% (95%
      credible interval [CrI] 4.0-15.8) and mortality would be 34.0% (30.3-39.6).
      Lowering the prevalence of diabetes by an absolute level of 6.6-13.8% could
      accelerate the decline of tuberculosis incidence by an absolute level of 11.5
      25.2% and tuberculosis mortality by 8.7-19.4%. Compared with the base case
      scenario, stopping the rise of diabetes would avoid 6.0 million (95% CrI 5.1-6.9)
      incident cases and 1.1 million (1.0-1.3) tuberculosis deaths in 13 countries
      during 20 years. If interventions reduce diabetes incidence by 35% by 2025, 7.8
      million (6.7-9.0) tuberculosis cases and 1.5 million (1.3-1.7) tuberculosis
      deaths could be averted by 2035. INTERPRETATION: The diabetes epidemic could
      substantially affect tuberculosis epidemiology in high burden countries. The
      communicable disease and non-communicable disease sectors need to move beyond
      conventional boundaries and link with each other to form a joint response to
      diabetes and tuberculosis. FUNDING: Taiwan National Science Council.

PMID- 25754416
TI  - To mix or to separate: that is the question.

PMID- 25754417
TI  - Evaluation of protective effect of freeze-dried strawberry, grape, and blueberry
      powder on acrylamide toxicity in mice.
AB  - Berries are dietary plants with high antioxidant activity. The aim of this study
      is to investigate the protective effect of berries (strawberry, grape, and
      blueberry) against the acrylamide (AA)-induced general toxicity, genotoxicity,
      and reproductive toxicity in mice model, respectively. Mice were treated with 50
      mg/kg b.w./day AA intraperitoneal injection for 5 d after feeding control diet or
      diet containing freeze-dried strawberry, grape, and blueberry powder. The results
      showed that AA induced a significant general toxicity, genotoxicity, and
      reproductive toxicity in mice. Compared with the control diet, the diets
      containing berries could reverse the AA-induced alterations in liver antioxidant
      enzymes activities (P < 0.05). Moreover, the AA-induced genotoxicity could be
      prevented by the diet containing berries. The DNA damage in the lymphocyte and
      liver cells and the micronucleus formation in bone marrow cell were significantly
      alleviated (P < 0.05). Meanwhile, the mice fed with diets containing berries
      showed a recovery in the sperm count, the sperm activity rate, sperm motility
      parameters, and the abnormal sperm rate (P < 0.05). Berry powders have remarkable
      intervention against the AA-induced general toxicity, genotoxicity, reproductive
      toxicity. Abundant phenolics, especially anthocyanins, may contribute to the
      intervention. 

PMID- 25754418
TI  - Tolerance of platelet concentrates treated with UVC-light only for pathogen
      reduction--a phase I clinical trial.
AB  - BACKGROUND: The THERAFLEX UV-Platelets pathogen reduction system for platelet
      concentrates (PCs) operates with ultraviolet C light (UVC; 254 nm) only without
      addition of photosensitizers. This phase I study evaluated safety and
      tolerability of autologous UVC-irradiated PCs in healthy volunteers. METHODS:
      Eleven volunteers underwent two single (series 1 and 2) and one double apheresis
      (series 3). PCs were treated with UVC, stored for 48 h and retransfused in a dose
      escalation scheme: 12.5, 25% and 50% of a PC (series 1); one complete PC (series
      2); two PCs (series 3). Platelet counts, fibrinogen, activated partial
      thromboplastin time, prothrombin time, D-dimer, standard haematology,
      temperature, heart rate, blood pressure and clinical chemistry parameters were
      measured. One- and 24-h corrected count increments were determined in series 2
      and 3. Platelet-specific antibodies were assessed before and at the end of the
      study. RESULTS: Neither adverse reactions related to transfusions nor antibodies
      against UVC-treated platelets were observed. Corrected count increments did not
      differ between series 2 and 3. CONCLUSIONS: Repeated transfusions of autologous
      UVC-treated PCs were well tolerated and did not induce antibody responses in all
      volunteers studied. EudraCT No. 2010-023404-26.

PMID- 25754419
TI  - Early development and neurogenesis of Temnopleurus reevesii.
AB  - Sea urchins are model non-chordate deuterostomes, and studying the nervous system
      of their embryos can aid in the understanding of the universal mechanisms of
      neurogenesis. However, despite the long history of sea urchin embryology
      research, the molecular mechanisms of their neurogenesis have not been well
      investigated, in part because neurons appear relatively late during
      embryogenesis. In this study, we used the species Temnopleurus reevesii as a new
      sea urchin model and investigated the detail of its development and neurogenesis
      during early embryogenesis. We found that the embryos of T. reevesii were
      tolerant of high temperatures and could be cultured successfully at 15-30 degrees
      C during early embryogenesis. At 30 degrees C, the embryos developed rapidly
      enough that the neurons appeared at just after 24 h. This is faster than the
      development of other model urchins, such as Hemicentrotus pulcherrimus or
      Strongylocentrotus purpuratus. In addition, the body of the embryo was highly
      transparent, allowing the details of the neural network to be easily captured by
      ordinary epifluorescent and confocal microscopy without any additional
      treatments. Because of its rapid development and high transparency during
      embryogenesis, T. reevesii may be a suitable sea urchin model for studying
      neurogenesis. Moreover, the males and females are easily distinguishable, and the
      style of early cleavages is intriguingly unusual, suggesting that this sea urchin
      might be a good candidate for addressing not only neurology but also cell and
      developmental biology. 

PMID- 25754420
TI  - CHX14 is a plasma membrane K-efflux transporter that regulates K(+)
      redistribution in Arabidopsis thaliana.
AB  - Potassium (K(+) ) is essential for plant growth and development, yet the
      molecular identity of many K(+) transporters remains elusive. Here we
      characterized cation/H(+) exchanger (CHX) 14 as a plasma membrane K(+)
      transporter. CHX14 expression was induced by elevated K(+) and histochemical
      analysis of CHX14 promoter::GUS transgenic plants indicated that CHX14 was
      expressed in xylem parenchyma of root and shoot vascular tissues of seedlings.
      CHX14 knockout (chx14) and CHX14 overexpression seedlings displayed different
      growth phenotypes during K(+) stress as compared with wild-type seedlings. Roots
      of mutant seedlings displayed higher K(+) uptake rates than wild-type roots.
      CHX14 expression in yeast cells deficient in K(+) uptake renders the mutant cells
      more sensitive to deficiencies of K(+) in the medium. CHX14 mediates K(+) efflux
      in yeast cells loaded with high K(+) . Uptake experiments using (86) Rb(+) as a
      tracer for K(+) with both yeast and plant mutants demonstrated that CHX14
      expression in yeast and in planta mediated low-affinity K(+) efflux. Functional
      green fluorescent protein (GFP)-tagged versions of CHX14 were localized to both
      the yeast and plant plasma membranes. Taken together, we suggest that CHX14 is a
      plasma membrane K(+) efflux transporter involved in K(+) homeostasis and K(+)
      recirculation.

PMID- 25754421
TI  - Improving the outcome for children with cancer: Development of targeted new
      agents.
AB  - The outcome for children with cancer has improved significantly over the past 60
      years, with greater than 80% of patients today becoming 5-year survivors. Despite
      this progress, cancer remains the leading cause of death from disease in children
      in the United States, and significant short-term and long-term treatment
      toxicities continue to impact the majority of children with cancer. The
      development of targeted new agents offers the prospect of potentially more
      effective and less toxic treatment for children. More than a decade since
      imatinib mesylate was introduced into the treatment of children with Philadelphia
      chromosome-positive acute lymphoblastic leukemia, transforming its outcome, a
      range of targeted agents has undergone study in pediatric cancer patients. Early
      lessons learned from these studies include a better understanding of the adverse
      event profile of these drugs in children, the challenge of developing pediatric
      specific formulations, and the continued reliance on successful development for
      adult cancer indications on pediatric drug development. The collaborative
      research infrastructure for children with cancer in the United States is well
      positioned to advance novel treatments into clinical investigations for a
      spectrum of rare and ultra-rare childhood cancers. A greater investment of
      resources in target discovery and validation can help drive much needed
      development of new, more effective treatments for children with cancer.

PMID- 25754422
TI  - High-resolution skim genotyping by sequencing reveals the distribution of
      crossovers and gene conversions in Cicer arietinum and Brassica napus.
AB  - KEY MESSAGE: We characterise the distribution of crossover and non-crossover
      recombination in Brassica napus and Cicer arietinum using a low-coverage
      genotyping by sequencing pipeline SkimGBS. The growth of next-generation DNA
      sequencing technologies has led to a rapid increase in sequence-based genotyping
      for applications including diversity assessment, genome structure validation and
      gene-trait association. We have established a skim-based genotyping by sequencing
      method for crop plants and applied this approach to genotype-segregating
      populations of Brassica napus and Cicer arietinum. Comparison of progeny
      genotypes with those of the parental individuals allowed the identification of
      crossover and non-crossover (gene conversion) events. Our results identify the
      positions of recombination events with high resolution, permitting the mapping
      and frequency assessment of recombination in segregating populations.

PMID- 25754423
TI  - Marker-assisted breeding for transgressive seed protein content in soybean
      [Glycine max (L.) Merr].
AB  - KEY MESSAGE: After two cycles of marker-assisted breeding on three loci, lines
      with transgressive segregation of 8.22-9.32 % protein content were developed
      based on four original soybean parents with 35.35-44.83 % protein content. Marker
      assisted breeding has been an innovative approach in conventional breeding, which
      is to be further demonstrated, especially for quantitative traits. A study on
      continuous transgressive breeding for seed protein content (SPC) in soybean using
      marker-assisted procedures is reported here. The SPC of the recombinant inbred
      line (RIL) population XG varied in 38.04-47.54 % under five environments with P 1
      of 35.35 %, P 2 of 44.34 % and total heritability of 89.11 %. A transgressive
      segregant XG30 with SPC 45.53 % was selected for further improvement. The linkage
      mapping of XG showed its genetic constitution composed of five additive QTL
      (32.16 % of phenotypic variation or PV) and two pairs of epistatic QTL (2.96 %
      PV) using 400 SSR markers with the remnant heritability 53.99 % attributed to the
      undetected collective of minor QTL. Another transgressive segregant WT133 with
      SPC 48.39 % was selected from the RIL population WT (44.83 % SPC for both
      parents). XG30 and WT133 were genotyped on the three major additive QTL (Prot-08
      1, Prot-14-1 and Prot-19-2) as A 2 A 2 B 2 B 2 L 1 L 1 and A 1 A 1 B 1 B 1 L 2 L
      2 , respectively. From WT133*XG30, surprising transgressive progenies were
      obtained, among which the recombinants with all three positive alleles A 2 _B 2
      _L 2 _ performed the highest SPC, especially that of Prot-08-1. The five F 2
      derived superior families showed their means higher than the high parent value in
      F 2:3 and F 2:4 and more transgressive effect in F 2:5:6, with the highest as
      high as 54.15 %, or 4.82 and 9.32 % more than WT133 and its original high parent,
      respectively. This study demonstrated the efficiency of marker-assisted procedure
      in breeding for transgressive segregation of quantitative trait.

PMID- 25754425
TI  - Merkel cell carcinoma: A case of palliative upper limb amputation in a patient
      with refractory in-transit metastases.
AB  - We report an unusual case of Merkel cell carcinoma in a 70-year-old woman with
      the rapid development of left upper limb in-transit and hepatic metastases. The
      patient had a preceding history of left-sided breast cancer. Palliative
      chemotherapy with carboplatin and etoposide produced a minimal response. The in
      transit metastases rapidly progressed and were refractory to chemotherapy and a
      single fraction of palliative radiotherapy, leading to a marked impact on her
      quality of life, secondary to sepsis and bleeding. After lengthy discussion, she
      consented to an above-elbow amputation resulting in a marked improvement in her
      well-being. In this case, we believe that palliative amputation of the involved
      arm was justified and beneficial to the patient. 

PMID- 25754424
TI  - Genome-wide association mapping for stripe rust (Puccinia striiformis F. sp.
      tritici) in US Pacific Northwest winter wheat (Triticum aestivum L.).
AB  - KEY MESSAGE: Potential novel and known QTL for race-specific all-stage and adult
      plant resistance to stripe rust were identified by genome-wide association
      mapping in the US PNW winter wheat accessions. Stripe rust (Puccinia striiformis
      F. sp. tritici; also known as yellow rust) is a globally devastating disease of
      wheat (Triticum aestivum L.) and a major threat to wheat production in the US
      Pacific Northwest (PNW), therefore both adult plant and all-stage resistance have
      been introduced into the winter wheat breeding programs in the PNW. The goal of
      this study was to identify quantitative trait loci (QTL) and molecular markers
      for these resistances through genome-wide association (GWAS) mapping in winter
      wheat accessions adapted to the PNW. Stripe rust response for adult plants was
      evaluated in naturally occurring epidemics in a total of nine environments in
      Washington State, USA. Seedling response was evaluated with three races under
      artificial inoculation in the greenhouse. The panel was genotyped with the 9K
      Illumina Wheat single nucleotide polymorphism (SNP) array and additional markers
      linked to previously reported genes and QTL for stripe rust resistance. The
      population was grouped into three sub-populations. Markers linked to Yr17 and
      previously reported QTL for stripe rust resistance were identified on chromosomes
      1B, 2A, and 2B. Potentially novel QTL associated with race-specific seedling
      response were identified on chromosomes 1B and 1D. Potentially novel QTL
      associated with adult plant response were located on chromosomes 2A, 2B, 3B, 4A,
      and 4B. Stripe rust was reduced when multiple alleles for resistance were
      present. The resistant allele frequencies were different among sub-populations in
      the panel. This information provides breeders with germplasm and closely linked
      markers for stripe rust resistance to facilitate the transfer of multiple loci
      for durable stripe rust resistance into wheat breeding lines and cultivars.

PMID- 25754426
TI  - Two-stage closed sinus lift: a new surgical technique for maxillary sinus floor
      augmentation.
AB  - Bone tissue atrophy may constitute a relative contraindication for implantation.
      The methods used in reconstruction of the alveolar ridge within the lateral
      section of the maxilla have been well known but not perfect. Presentation of the
      two-stage, closed sinus lift technique as well as efficacy evaluation of
      reconstruction of the alveolar ridge in the maxilla within its vertical dimension
      with the use of this technique. The total procedure was performed in 26 out of 28
      patients qualified for the study. The height of the alveolar ridge at the site of
      the planned implantation was no <3 mm, the width of the ridge was no <5 mm.
      During the treatment stage 1 the sinus lift was performed for the first time. The
      created hollow was filled with allogeneic granulate. After 3-6 months stage 2 was
      performed consisting in another sinus lift with simultaneous implantation. The
      treatment was completed with prosthetic restoration after 6 months of
      osteointegration. In 24 out of 26 cases stage 1 was completed with the average
      ridge height of 7.2 mm. In stage 2, simultaneously with the second sinus lift, 26
      implants were placed and no cases of sinusitis were found. In the follow-up
      period none of the implants were lost. The presented method is efficient and
      combines the benefits of the open technique-allowing treatment in cases of larger
      reduction of the vertical dimension and the closed technique-as it does not
      require opening of the maxillary sinus. 

PMID- 25754427
TI  - Avian influenza virus infection risk in humans with chronic diseases.
AB  - Saliva proteins may protect older people from influenza, however, it is often
      noted that hospitalizations and deaths after an influenza infection mainly occur
      in the elderly population living with chronic diseases, such as diabetes and
      cancer. Our objective was to investigate the expression level of the terminal
      alpha2-3- and alpha2-6-linked sialic acids in human saliva from type 2 diabetes
      mellitus (T2DM), liver disease and gastric cancer (GC) patients and assess the
      binding activity of these linked sialic acids against influenza A viruses (IAV).
      We observed that the expression level of the terminal alpha2-3-linked sialic
      acids of elderly individuals with T2DM and liver disease were down-regulated
      significantly, and the terminal alpha2-6 linked sialic acids were up-regulated
      slightly or had no significant alteration. However, in the saliva of patients
      with GC, neither sialic acid was significantly altered. These findings may reveal
      that elderly individuals with chronic diseases, such as diabetes and liver
      disease, might be more susceptible to the avian influenza virus due to the
      decreased expression of terminal alpha2-3-linked sialic acids in their saliva. 

PMID- 25754429
TI  - Editor's perspectives - March 2015.

PMID- 25754428
TI  - A pilot study examining diagnostic differences among exercise and weight
      suppression in bulimia nervosa and binge eating disorder.
AB  - OBJECTIVE: The objective of this study was to investigate diagnostic differences
      in weight suppression (e.g., the difference between one's current body weight and
      highest non-pregnancy adult body weight) and exercise among Bulimia Nervosa (BN)
      and Binge Eating Disorder (BED). Because exercise may be a key contributor to
      weight suppression in BN, we were interested in examining the potential
      moderating effect of exercise on weight suppression in BN or BED. METHOD:
      Participants with BN (n = 774) and BED (n = 285) completed self-report surveys of
      weight history, exercise and eating disorder symptoms. Generalised linear model
      analyses were used to examine the associations among diagnosis, exercise
      frequency and their interaction on weight suppression. RESULTS: Exercise
      frequency and BN/BED diagnosis were both associated with weight suppression.
      Additionally, exercise frequency moderated the relationship between diagnosis and
      weight suppression. Specifically, weight suppression was higher in BN than in BED
      among those with low exercise frequency but comparable in BN and BED among those
      with high exercise frequency. DISCUSSION: Our results suggest that exercise
      frequency may contribute to different weight suppression outcomes among BN and
      BED. This may inform clinical implications of exercise in these disorders.
      Specifically, much understanding of the differences among exercise frequency and
      the compensatory use of exercise in BN and BED is needed.

PMID- 25754430
TI  - Combination therapy with zinc gluconate and PUVA for alopecia areata totalis: an
      adjunctive but crucial role of zinc supplementation.
AB  - Spontaneous remission occurs in less than 10% of patients suffering from alopecia
      areata (AA) totalis for more than 2 years. The efficacy of PUVA therapy is
      controversial due to recurrence of hair loss after cessation. We report two cases
      presenting with AA totalis and AA universalis. After hair regrowth, relapse of
      hair loss occurred upon cessation of PUVA and zinc gluconate combination therapy.
      However, hair regrowth was noted upon the reintroduction of zinc gluconate and
      sulfur amino acids without PUVA in the first case and with episodic PUVA in the
      second case. The chronology of events appears to support the notion that zinc has
      a significant effect. Our findings suggest the possibility of a subgroup of zinc
      responsive patients, but the identification of these patients remains difficult.
      Metallothioneins and zinc transporters regulating the entrance and exit of zinc
      in cells might play a key role. Combination therapy with immunomodulators may be
      administered to facilitate enhanced zinc-targeted action. Taking into account the
      safety profile of zinc, 30-40 mg/day of zinc metal may be used during at least 1
      year, although we recommend to monitor its serum and hair levels. Studies with a
      larger number of patients are required to further investigate the therapeutic
      effect of zinc. 

PMID- 25754431
TI  - Public Drug Coverage and Its Impact on Triptan Use Across Canada: A Population
      Based Study.
AB  - BACKGROUND: Public drug coverage for triptan medications varies across
      jurisdictions in Canada, which may lead to differences in usage patterns and
      patient risk for medication overuse headache. METHODS: We conducted a population
      based, cross-sectional analysis of publicly funded triptan use in seven provinces
      across Canada from January 1, 2012 to December 31, 2012. All patients who had
      filled at least one prescription for a triptan during the study period were
      included. We defined quantity limits of 6, 12, and 18 triptan units per month to
      assess the prevalence of high volumes of triptan use, which may place patients at
      risk for medication overuse headaches, and compared this prevalence between
      provinces with different funding restrictions. RESULTS: We identified 14,085
      publicly funded users of triptans in 2012 in the seven provinces studied, 82.5%
      of whom were aged less than 65 years (N = 11,631). The prevalence of triptan use
      ranged substantially by province, from 0.04% in Ontario to a maximum of 1.0% in
      Manitoba (P < .001). Furthermore, the percentage of patients in each province
      using more than 6, 12, or 18 units per month differed significantly between
      provinces (P < .001). In particular, the percentage of patients treated with more
      than 6 units per month ranged from as low as 2.1% in Saskatchewan to 43.8% in
      Ontario. CONCLUSIONS: Differing public drug reimbursement criteria for triptans
      may be one contributing factor that has led to our observation of considerable
      variation in both prevalence of triptan prescribing and potential overuse of
      these medications. We offer that monthly quantity limits may be considered as a
      tool to decrease risks for medication overuse headache.

PMID- 25754436
TI  - Influence of different dietary zinc levels on cashmere growth, plasma
      testosterone level and zinc status in male Liaoning Cashmere goats.
AB  - The experiment was conducted to investigate the influence of different levels of
      zinc (Zn) on cashmere growth, plasma testosterone and Zn profile in male Cashmere
      goats. Twenty-eight male Liaoning Cashmere goats, 3 years old and body weight at
      56.2 +/- 2.45 kg, were assigned to four groups. The animals were fed a basal diet
      containing of 45.9 mg Zn/kg dry matter (DM) basis and supplemented with 0, 20, 40
      or 80 mg Zn (reagent grade ZnSO4 .7H2 O) per kg DM for 90 days. There was no
      significant effect on growth and diameter of cashmere fibre for Zn supplemented
      in diets. However, the length and growth rate of wool were improved (p < 0.05)
      with dietary Zn. The length and growth rate of wool were higher (p < 0.05) for
      the groups supplemented with 40 or 80 mg Zn/kg DM compared with that of 20 mg
      Zn/kg DM treatment group. Plasma testosterone concentration was increased for Zn
      supplemented in diets, and the testosterone concentration was higher (p < 0.05)
      in goats fed on the diet supplemented with 40 or 80 mg Zn/kg DM compared with
      those fed on basal diet. Plasma Zn concentrations increased (p < 0.05) with
      increasing dietary Zn and supplemented with 40 and 80 mg Zn/kg DM groups improved
      plasma Zn concentration (p < 0.05) more than 20 mg Zn/kg DM group. Fibre Zn
      content was higher (p < 0.05) in groups supplemented with 40 or 80 mg Zn/kg DM
      compared with control group, but no difference between Zn-supplemented groups (p
      > 0.05). The activity of plasma alkaline phosphatase was increased (p < 0.05) due
      to dietary Zn supplementation; however, no difference was found between
      supplemented treatment groups (p > 0.05). In conclusion, Zn content (45.9 mg
      Zn/kg DM) in control diet was insufficient for optimal wool growth performance,
      and we recommended the level of dietary Zn for such goats is 86 mg/kg DM during
      the breeding season and cashmere fibre growing period.

PMID- 25754437
TI  - An Analysis of Reliability and Accuracy of Muscle Thickness Ultrasonography in
      Critically Ill Children and Adults.
AB  - BACKGROUND: Muscle wasting starts already within the first week in critically
      patients and is strongly related to poor outcome. Nevertheless, the early
      detection of muscle wasting is difficult. Therefore, we investigated the
      reliability and accuracy of ultrasonography to evaluate skeletal muscle wasting
      in critically ill children and adults. METHODS: This prospective observational
      study enrolled 30 sedated critically ill children and 14 critically ill adults.
      Two independent investigators made 210 ultrasonographical assessments of muscle
      thigh thickness. Inter- and intraobserver reliability and cutoff levels were
      calculated as a function of muscle thickness and the expected reduction in muscle
      size (predefined at 20% and 30%). RESULTS: Mean +/- SD muscle thickness was 1.67
      +/- 0.55 cm in the pediatric and 2.10 +/- 0.85 cm in the adult population. The
      median absolute interobserver variability was 0.07 cm (interquartile range [IQR],
      0.04-0.20 cm) in the pediatric population and 0.05 cm (IQR, 0.03-0.09 cm) in the
      adult population. However, the absolute intraobserver accuracy had a 95%
      confidence interval of 0.43 cm in children and 0.22 cm in adults. Only a 30%
      decrease (0.50 cm) in muscle thickness can be detected in critically ill
      children. CONCLUSION: Although the interobserver variability is acceptable in the
      pediatric population, the intraobserver variability is too large with respect to
      the expected reduction in muscle thickness. In adults, ultrasonography may be a
      reliable tool for early detection of muscle mass wasting.

PMID- 25754438
TI  - Japanese Kampo Saireito Has a Liver-Protective Effect Through the Inhibition of
      Inducible Nitric Oxide Synthase Induction in Primary Cultured Rat Hepatocytes.
AB  - BACKGROUND: Japanese herbal medicine, Kampo saireito, is used for treatments in
      patients with digestive diseases, including chronic hepatitis and cirrhosis.
      However, few studies demonstrate scientific evidence for liver-protective effects
      of saireito. In inflamed liver, proinflammatory cytokines such as tumor necrosis
      factor (TNF)-alpha and interleukin (IL)-1beta stimulate the induction of
      inducible nitric oxide synthase (iNOS) and nitric oxide (NO) production.
      Excessive levels of NO synthesized by iNOS have been implicated as one of the
      factors in liver injury, so it is essential to reduce the induction of iNOS for
      the prevention of liver injury. In this study, we examined IL-1beta-stimulated
      hepatocytes as a simple "in vitro injury model" to investigate liver-protective
      effects of saireito. METHOD: Primary cultured rat hepatocytes were treated with
      IL-1beta in the presence or absence of saireito. The induction of NO production
      and iNOS and its signaling pathway were analyzed. RESULTS: Saireito inhibited the
      production of NO dose and time dependently and reduced the expression of iNOS
      messenger RNA (mRNA) and its protein. Saireito had no effect on IkappaB
      degradation but inhibited the translocation of nuclear factor (NF)-kappaB to the
      nucleus and its DNA binding. Saireito also inhibited the activation of Akt,
      resulting in the reduction of type I IL-1 receptor (IL-1RI) mRNA and protein
      expression. CONCLUSION: These findings demonstrate that saireito suppresses iNOS
      gene expression through the inhibition of NF-kappaB and IL-1RI-dependent
      pathways, leading to the reduction of NO production. Saireito may have
      therapeutic potential for organ injuries, including liver.

PMID- 25754439
TI  - Validation Study of Energy Requirements in Critically Ill, Obese Cancer Patients.
AB  - BACKGROUND: Current guidelines from the American Society for Parenteral and
      Enteral Nutrition and the Society of Critical Care Medicine (ASPEN/SCCM)
      regarding caloric requirements and the provision of nutrition support in
      critically ill, obese adults may not be suitable for similar patients with
      cancer. We sought to determine whether the current guidelines accurately estimate
      the energy requirements, as measured by indirect calorimetry (IC), of critically
      ill, obese cancer patients. MATERIALS AND METHODS: This was a retrospective
      validation study of critically ill, obese cancer patients from March 1, 2007, to
      July 31, 2010. All patients >=18 years of age with a body mass index (BMI) >=30
      kg/m(2) who underwent IC were included. We compared the measured energy
      expenditure (MEE) against the upper limit of the recommended guideline (25
      kcal/kg of ideal body weight [IBW]) and MEE between medical and surgical patients
      in the intensive care unit. RESULTS: Thirty-three patients were included in this
      study. Mean MEE (28.7 +/- 5.2 kcal/kg IBW) was significantly higher than 25
      kcal/kg IBW (P < .001), and 78% of patients had nutrition requirements greater
      than the current guideline recommendations. No significant differences in MEE
      between medical and surgical patients in the ICU were observed. CONCLUSIONS:
      Critically ill, obese cancer patients require more calories than the current
      guidelines recommend, likely due to malignancy-associated metabolic variations.
      Our results demonstrate the need for IC studies to determine the energy
      requirements in these patients and for reassessment of the current
      recommendations.

PMID- 25754440
TI  - Gastrojejunostomy Tube Bowel Perforations in Low-Weight Infants.
AB  - This is a case series in which 3 infants with gastrojejunostomy tube (GJT)
      insertion developed delayed perforation secondary to pressure necrosis. A review
      of all patients who underwent a GJT placement in 2013 was performed. Three of
      these patients developed surgically confirmed perforation secondary to pressure
      necrosis during this time period; no patients developed perforation at the time
      of GJT insertion. The indications for GJT insertion for all 3 patients were
      severe gastroesophageal reflux disease; 2 patients also had recurrent aspiration.
      The patients were between 9 weeks and 10 months of age at the time of GJT
      insertion. The site of perforation for all 3 cases occurred just distal to the
      ligament of Treitz between 48 and 72 hours following insertion. Given our 3 cases
      of perforation in patients weighing <10 kg, there may be a higher risk of
      perforation in low-weight patients.

PMID- 25754442
TI  - Effect of temperature and loading on the structure of beta-casein/ibuprofen
      assemblies.
AB  - beta-Casein is a 24 kDa amphiphilic and unstructured protein that self-assembles
      into small core-shell micelles at a wide range of concentrations, pH values and
      temperatures. We recently developed the micelles as nanocarriers for oral
      delivery of hydrophobic drugs. In this paper we examined the effect of the
      hydrophobic non-steroidal anti-inflammatory drug (NSAID) ibuprofen on the
      micellar structure, as a function of temperature and loading. Using cryo
      transmission electron microscopy (cryo-TEM) we find two routes of organization -
      mixed micellization and co-assembly (aggregation). The time-dependent events that
      characterize the second routes has been examined in detail. At 25  degrees C we
      find coexistence of small assemblies and larger aggregates of irregular (but
      defined) structures that contain the drug. Increasing the drug loading increases
      the relative number of the larger aggregates and their dimensions, leading
      eventually to the formation of long then branched structures, like in amphiphilic
      block copolymer solutions. Similar trends were identified for changes in the
      temperature. Combined, our results suggest that ibuprofen acts as a co-surfactant
      that possibly is localizes to the interface rather than being encapsulated in the
      micellar core as other NSAID hydrophobic drugs.

PMID- 25754441
TI  - Responses of Preterm Pigs to an Oral Fluid Supplement During Parenteral
      Nutrition.
AB  - BACKGROUND: Nutrients and electrolytes in amniotic fluid swallowed by fetuses are
      important for growth and development. Yet, preterm infants requiring parenteral
      nutrition (PN) receive minimal or no oral inputs. With the limited availability
      of amniotic fluid, we evaluated the responses of preterm pigs receiving PN to an
      oral fluid supplement (OFS) based on the electrolyte and nutrient composition of
      amniotic fluid. MATERIALS AND METHODS: Preterm pigs (92% of term) received a
      combination of PN (6 mL/kg-h) and 4 mL/kg-h of supplemental fluid as an
      experimental OFS (n = 9), lactated Ringer's either enterally (n = 10) or
      intravenously (n = 8). Outcome measures after 96 hours were weight gain, blood
      chemistry, organ weights, and small intestine mass and brush-border membrane
      carbohydrases. RESULTS: The OFS did not improve weight gain compared with
      providing lactated Ringer's orally or intravenously, or increase serum urea
      nitrogen values, but resulted in higher serum total and low-density lipoprotein
      cholesterol, as well as improved glucoregulation and heavier intestines, livers,
      kidneys, and brains and lighter lungs. CONCLUSIONS: Providing supplemental fluid
      and electrolytes during PN either intravenously or orally increases weight gain
      after preterm birth. An oral fluid supplement based on amniotic fluid may
      accelerate development and maturation of organs critical for extrauterine life
      after preterm birth and may enhance neurodevelopment.

PMID- 25754443
TI  - Upscaling the recruitment and retention of human resources for health at primary
      healthcare centres in Lebanon: a qualitative study.
AB  - The sustainability of primary healthcare (PHC) worldwide has been challenged by a
      global shortage in human resources for health (HRH). This study is a unique
      attempt at systematically soliciting and synthesising the voice of PHC and
      community stakeholders on the HRH recruitment and retention strategies at the PHC
      sector in Lebanon, the obstacles and challenges hindering their optimisation and
      the recommendations to overcome such obstacles. A qualitative design was
      utilised, involving 22 semi-structured interviews with PHC experts in Lebanon
      conducted in 2013. Nvivo qualitative data analysis software was employed for the
      thematic analysis of data collected from interviews. Five comprehensive themes
      emerged: understanding PHC scope, HRH recruitment issues, HRH retention
      challenges, rural areas' specific challenges and stakeholders' recommendations.
      Analysis of stakeholders' responses revealed a lack of a unified understanding of
      the PHC scope impacting the capacity for appropriate HRH planning. Identified
      impediments to recruitment included the suboptimal supply of HRH, financial
      constraints and poor management. Retention difficulties were attributed to poor
      working environments, financial constraints and lack of professional development.
      There was consensus that HRH challenges faced were aggravated in rural areas,
      jeopardising the equitable access to PHC services of quality. Equitable access
      was also jeopardised by the reported shortage of female HRH in a sociocultural
      context where many females prefer providers of the same gender. The study sets
      the path towards upscaling recruitment and retention policies and practices
      through the endorsement of a nationally acknowledged PHC definition and scope,
      the sustainable development of the PHC workforce and through the implementation
      of targeted recruitment and retention strategies addressing rural settings and
      gender equity. Decision-makers and planners are urged to identify HRH as the most
      important input for the success of PHC programmes and interventions, especially
      in the growing fields of mental health and geriatric care. 

PMID- 25754444
TI  - Authentication of commercial candy ingredients using DNA PCR-cloning methodology.
AB  - BACKGROUND: Commercial candies are consumed by all population age sectors
      worldwide. Methods for quality control and composition authentication are
      therefore needed for best compliance with consumers' preferences. In this study
      applications of DNA-based methodology for candy quality control have been tested.
      Eighteen samples of commercial candies (marshmallows, gumdrops, jelly, sherbet,
      gelatin-based desserts) produced by five countries were analyzed to identify the
      component species by polymerase chain reaction, cloning and sequencing of 16S
      rRNA and ribulose -1,5-diphosphate carboxylase oxygenase genes, and the species
      determined from BLAST comparison with universal databases and phylogenetic
      analysis. RESULTS: Positive DNA extraction and amplification of the target genes
      were obtained for 94% of candies assayed, even those containing as little as
      <0.0005 ng uL(-1) DNA concentration. The results demonstrated that the species
      detected from DNA were compatible with the information provided on candy labels
      only in a few products. DNA traces of undeclared species, including fish, were
      found in most samples, and two products were labeled as vegetarian but contained
      porcine DNA. CONCLUSION: Based on the inaccuracy found on the labels of sweets we
      recommend the use of DNA tests for quality control of these popular sweets. DNA
      tests have been useful in this field but next-generation sequencing methods could
      be more effective.

PMID- 25754445
TI  - Exploring stroke survivor experience of participation in an enriched environment:
      a qualitative study.
AB  - BACKGROUND: Data highlight the importance of undertaking intense and frequent
      repetition of activities within stroke rehabilitation to maximise recovery. An
      enriched environment (EE) provides a medium in which these activities can be
      performed and enhanced recovery achieved. An EE has been shown to promote
      neuroplasticity in animal models of stroke, facilitating enhanced recovery of
      motor and cognitive function. However, the benefit of enriching the environment
      of stroke survivors remains unknown. AIM: To qualitatively explore stroke
      survivors' experience of implementation of exposure to an EE within a typical
      stroke rehabilitation setting, in order to identify facilitators and barriers to
      participation. METHODS: Semi-structured interviews with 10 stroke survivors (7
      females and 3 males, mean age of 70.5 years) exposed to an EE for a 2-week period
      following exposure to routine rehabilitation within a stroke rehabilitation ward.
      An inductive thematic approach was utilised to collect and analyse data. RESULTS:
      Qualitative themes emerged concerning the environmental enrichment paradigm
      including: (1) "It got me moving" - perceived benefits of participation in an EE;
      (2) "You can be bored or you can be busy." - Attenuating factors influencing
      participation in an EE; (3) "I don't like to make the staff busier" - limitations
      to use of the EE. CONCLUSIONS: This study provides preliminary support for the
      implementation of an EE within a typical stroke rehabilitation setting from a
      patient perspective. Reported benefits included (1) increased motor, cognitive
      and sensory stimulation, (2) increased social interaction, (3) alleviation of
      degree of boredom and (4) increased feelings of personal control. However,
      participants also identified a number of barriers affecting implementation of the
      EE. We have previously published findings on perceptions of nursing staff working
      with stroke survivors in this enriched rehabilitation environment who identified
      that patients benefited from having better access to physical, cognitive and
      social activities. Together, results contribute to valuable evidence for future
      implementation of an EE in stroke rehabilitation settings. Implications for
      Rehabilitation Stroke survivor access to an enriched environment (EE): RESULTS
      identified that participation in both individual and communal forms of
      environment enrichment within the stroke rehabilitation ward resulted in
      increased access to activities providing increased opportunities for enhanced
      motor, cognitive and sensory stimulation. Increased access to and participation
      in activities of the environmental enrichment (individual and communal)
      interrupted the ongoing cycle of boredom and inactivity experienced by many
      participants. This study provides preliminary support for the implementation of
      an EE within a typical stroke rehabilitation setting from a patient perspective.

PMID- 25754446
TI  - Permeation study of indomethacin from polycarbazole/natural rubber blend film for
      electric field controlled transdermal delivery.
AB  - Transdermal drug delivery is an alternative route to transport the drug into the
      blood system. This method has been continuously developed to overcome limitations
      and is now suitable for a wide variety of drug molecules. In this work, the
      influences of electric field and conductive polymer were investigated for
      developing a unique drug delivery system from double-centrifuged natural rubber
      (DCNR) matrix. Indomethacin (IN) was loaded into polycarbazole (PCz) as a
      conductive polymer drug host to promote the efficient transportation of the drug.
      The IN-loaded PCz was blended with DCNR to form a transdermal patch. The
      permeation of IN through the PCz/NR film and pig skin was carrried out by a
      modified Franz diffusion cell. The IN diffused from DCNR film by the diffusion
      controlled combined with erosion mechanism depending on the pore formation
      period. The drug permeation increased with decreasing cross-link ratio because of
      more accessible pathways for the drug permeation. Moreover, an electric field and
      the inclusion of PCz as the drug carrier dramatically improved the diffusion of
      the drug from the membrane by through the electrorepulsive force and electro
      reduced PCz expansion. Thus, the PCz/DCNR films are shown here as a potential
      transdermal patch under applied electric field.

PMID- 25754448
TI  - Yves chauvin (1930-2015).

PMID- 25754447
TI  - Absence of glia maturation factor protects dopaminergic neurons and improves
      motor behavior in mouse model of parkinsonism.
AB  - Previously, we have shown that aberrant expression of glia maturation factor
      (GMF), a proinflammatory protein, is associated with the neuropathological
      conditions underlying diseases suggesting an important role for GMF in
      neurodegeneration. In the present study, we demonstrate that absence of GMF
      suppresses dopaminergic (DA) neuron loss, glial activation, and expression of
      proinflammatory mediators in the substantia nigra pars compacta (SN) and striatum
      (STR) of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) treated mice.
      Dopaminergic neuron numbers in the SN and fiber densities in the STR were reduced
      in wild type (Wt) mice when compared with GMF-deficient (GMF-KO) mice after MPTP
      treatment. We compared the motor abnormalities caused by MPTP treatment in Wt and
      GMF-KO mice as measured by Rota rod and grip strength test. Results show that the
      deficits in motor coordination and decrease in dopamine and its metabolite
      content were protected significantly in GMF-KO mice after MPTP treatment when
      compared with control Wt mice under identical experimental conditions. These
      findings were further supported by the immunohistochemical analysis that showed
      reduced glial activation in the SN of MPTP-treated GMF-KO mice. Similarly, in
      MPTP-treated GMF-KO mice, production of inflammatory tumor necrosis factor alpha,
      interleukine-1 beta, granulocyte macrophage-colony stimulating factor, and the
      chemokine (C-C motif) ligand 2 MCP-1 was suppressed, findings consistent with a
      role for GMF in MPTP neurotoxicity. In conclusion, present investigation provides
      the first evidence that deficiency of GMF protects the DA neuron loss and reduces
      the inflammatory load following MPTP administration in mice. Thus depletion of
      endogenous GMF represents an effective and selective strategy to slow down the
      MPTP-induced neurodegeneration. 

PMID- 25754449
TI  - Incremental value of live/real time three-dimensional transesophageal
      echocardiography over the two-dimensional modality in the assessment of cardiac
      lymphoma.
AB  - We describe a case of cardiac lymphoma where live/real time three-dimensional
      transesophageal echocardiography provided additional information compared to two
      dimensional transesophageal echocardiography regarding the extent of tumor
      infiltration. In addition, it gave a quantitative assessment of the tumor burden
      by providing its volume. 

PMID- 25754450
TI  - The SCN1A mutation database: updating information and analysis of the
      relationships among genotype, functional alteration, and phenotype.
AB  - Mutations in the SCN1A gene have been identified in epilepsy patients with widely
      variable phenotypes and modes of inheritance and in asymptomatic carriers. This
      raises challenges in evaluating the pathogenicity of SCN1A mutations. We
      systematically reviewed all SCN1A mutations and established a database containing
      information on functional alterations. In total, 1,257 mutations have been
      identified, of which 81.8% were not recurrent. There was a negative correlation
      between phenotype severity and missense mutation frequency. Further analyses
      suggested close relationships among genotype, functional alteration, and
      phenotype. Missense mutations located in different sodium channel regions were
      associated with distinct functional changes. Missense mutations in the pore
      region were characterized by the complete loss of function, similar to
      haploinsufficiency. Mutations with severe phenotypes were more frequently located
      in the pore region, suggesting that functional alterations are critical in
      evaluating pathogenicity and can be applied to patient management. A negative
      correlation was found between phenotype severity and familial incidence, and
      incomplete penetrance was associated with missense and splice site mutations, but
      not truncations or genomic rearrangements, suggesting clinical genetic counseling
      applications. Mosaic mutations with a load of 12.5-25.0% were potentially
      pathogenic with low penetrance, suggesting the need for future studies on less
      pathogenic genomic variations.

PMID- 25754451
TI  - Role of novel retroviruses in chronic liver disease: assessing the link of human
      betaretrovirus with primary biliary cirrhosis.
AB  - A human betaretrovirus resembling mouse mammary tumor virus has been
      characterized in patients with primary biliary cirrhosis. The agent triggers a
      disease-specific phenotype in vitro with aberrant cell-surface expression of
      mitochondrial antigens. The presentation of a usually sequestered self-protein is
      thought to lead to the loss of tolerance and the production of anti-mitochondrial
      antibodies associated with the disease. Similar observations have been made in
      mouse models, where mouse mammary tumor virus infection has been linked with the
      development of cholangitis and production of anti-mitochondrial antibodies. The
      use of combination antiretroviral therapy has been shown to impact on
      histological and biochemical disease in mouse models of autoimmune biliary
      disease and in clinical trials of patients with primary biliary cirrhosis.
      However, the HIV protease inhibitors are not well tolerated in patients with
      primary biliary cirrhosis, and more efficacious regimens will be required to
      clearly link reduction of viral load with improvement of cholangitis. 

PMID- 25754453
TI  - Effectiveness of mechanical chest compression for out-of-hospital cardiac arrest
      patients in an emergency department.
AB  - BACKGROUND: To increase the chance of restoring spontaneous circulation,
      cardiopulmonary resuscitation (CPR) with high-quality chest compressions is
      needed. We hypothesized that, in a municipal hospital emergency department, the
      outcome in nontraumatic out-of-hospital cardiac arrest patients treated with
      standard CPR followed by mechanical chest compression (MeCC) was not inferior to
      that followed by manual chest compression (MaCC). The purposes of the study were
      to test our hypothesis and investigate whether the use of MeCC decreased human
      power demands for CPR. METHODS: A total of 455 consecutive out-of-hospital
      cardiac arrest patients of presumed cardiac etiology were divided into two groups
      according to the chest compressions they received (MaCC or MeCC) in this
      retrospective review study. Human power demand for CPR was described according to
      the Basic Life Support/Advanced Cardiovascular Life Support guidelines and the
      device handbook. The primary endpoint was recovery of spontaneous circulation
      during resuscitation, and the secondary endpoints were survival to hospital
      admission and medical human power demands. RESULTS: In this study, recovery of
      spontaneous circulation was achieved in 33.3% of patients in the MeCC group and
      in 27.1% in the MaCC group (p = 0.154), and the percentages of patients who
      survived hospitalization were 22.2% and 17.6%, respectively (p = 0.229). A ratio
      of 2:4 for the human power demand for CPR between the groups was found.
      Independent predictors of survival to hospitalization were ventricular
      fibrillation/pulseless ventricular tachycardia as initial rhythm and recovery of
      spontaneous circulation. CONCLUSION: No difference was found in early survival
      between standard CPR performed with MeCC and that performed with MaCC. However,
      the use of the MeCC device appears to promote staff availability without waiving
      patient care in the human power-demanding emergency departments of Taiwan
      hospitals.

PMID- 25754454
TI  - Efficacy, safety, and tolerability of intravesically administered 0.1% oxybutynin
      hydrochloride solution in adult patients with neurogenic bladder: A randomized,
      prospective, controlled multi-center trial.
AB  - AIMS: To verify the efficacy, safety and tolerability of intravesical
      administration of 0.1% oxybutynin hydrochloride compared to its oral
      administration for treatment of neurogenic detrusor overactivity (NDO) in a
      randomized, prospective, controlled, open-label, multi-center trial in 35 adult
      patients. METHODS: NDO was confirmed within the previous 24 months by urodynamic
      studies (UDS). Group 1 (n = 18) received 10 ml 0.1% oxybutynin hydrochloride
      intravesically three times per day and group 2 (n = 17) 5 mg oxybutynin
      hydrochloride orally three times per day for a period of 28 days. Primary
      efficacy criterion was the change in the maximum bladder capacity between the
      beginning of the study and after 4 weeks as assessed by UDS. Adverse drug
      reactions (ADR) were collected and an evaluation of anticholinergic effects was
      conducted. RESULTS: The increase in maximum bladder capacity was 117 ml with
      intravesical application (P = 0.0002) versus 18 ml with the oral application (P =
      0.51). The difference was statistically significant (P = 0.0086). ADR were
      reported by 10 (55.6%) of patients with intravesical administration, and by 14
      (82.4%) of patients with oral administration. Significant differences in favor of
      the intravesical application were observed in ADR affecting vision (1/10 vs.
      9/14), gastrointestinal tract (8/10 vs. 14/14), nervous system (2/10 vs. 8/14),
      and skin and subcutis (1/10 vs. 6/14). No serious adverse drug reactions were
      reported. CONCLUSIONS: This study demonstrates the efficacy and safety of
      intravesical 0.1% oxybutynin hydrochloride in the treatment of NDO with respect
      to the increase in maximum bladder capacity. Neurourol. Urodynam. 35:582-588,
      2016. (c) 2015 Wiley Periodicals, Inc.

PMID- 25754452
TI  - What Role Does Mycobacterium avium subsp. paratuberculosis Play in Crohn's
      Disease?
AB  - Crohn's disease (CD) is a chronic, debilitating inflammatory bowel disease with
      no etiological agent yet identified. Studies have demonstrated that the bacterium
      Mycobacterium avium subsp. paratuberculosis (MAP) is present in a high percentage
      of CD patients. Although MAP has been isolated from human specimens, current
      techniques fail to show the presence of MAP in 100 % of tissues or biopsies
      obtained from CD patient lesions, and thus MAP cannot meet Koch's postulate as
      the etiological agent of CD. In this report, the effect of genetic and immune
      factors as well as the presence of MAP as a potential environmental factor is
      analyzed. 

PMID- 25754455
TI  - Transvesicoscopic ureteral reimplantation: Politano-Leadbetter versus Cohen
      technique.
AB  - OBJECTIVES: To compare the outcomes of the Politano-Leadbetter and Cohen
      techniques in laparoscopic pneumovesicum approach for ureteral reimplantation.
      METHODS: We retrospectively reviewed the medical records of 24 patients who
      underwent transvesicoscopic ureteral reimplantation during the period from 2007
      to 2014. The patients were treated with either the Cohen or Politano-Leadbetter
      technique. Operative duration, duration of hospital stay, and success and
      complication rates were compared. RESULTS: Operative duration was 1 h longer for
      the Politano-Leadbetter technique than for the Cohen technique (P < 0.05). Foley
      catheters were removed 2-3 days after the procedures. The mean hospital stay was
      3.6 days. Reflux completely resolved in 21 patients (35 ureters, 94.6%), but not
      in two patients (2 ureters). There was no difference in the success rate or
      durations of catheterization or hospital stay between patients treated with the
      Politano-Leadbetter technique and those treated with the Cohen technique.
      CONCLUSIONS: The Politano-Leadbetter and Cohen techniques are both reliable for
      transvesicoscopic ureteral reimplantation. Despite a longer operative time,
      because of the higher surgical complexity, the Politano-Leadbetter ureteral
      reimplantation offers important physiological advantages over other techniques.

PMID- 25754456
TI  - Social relationship difficulties in autism and reactive attachment disorder:
      Improving diagnostic validity through structured assessment.
AB  - BACKGROUND: Autism Spectrum Disorder (ASD) versus Reactive Attachment Disorder
      (RAD) is a common diagnostic challenge for clinicians due to overlapping
      difficulties with social relationships. RAD is associated with neglect or
      maltreatment whereas ASD is not: accurate differential diagnosis is therefore
      critical. Very little research has investigated the relationship between the two,
      and it is unknown if standardised measures are able to discriminate between ASD
      and RAD. The current study aimed to address these issues. METHODS: Fifty eight
      children with ASD, and no history of maltreatment, were group matched on age with
      67 children with RAD. Group profiles on multi-informant measures of RAD were
      investigated and group differences explored. Discriminant function analysis
      determined assessment features that best discriminated between the two groups.
      RESULTS: Although, according to parent report, children with ASD presented with
      significantly fewer indiscriminate friendliness behaviours compared to the RAD
      group (p<0.001), 36 children with ASD appeared to meet core RAD criteria.
      However, structured observation clearly demonstrated that features were
      indicative of ASD and not RAD for all but 1 of these 36 children. CONCLUSIONS:
      Children with RAD and children with ASD may demonstrate similar social
      relationship difficulties but there appears to be a difference in the social
      quality of the interactions between the groups. In most cases it was possible to
      differentiate between children with ASD and children with RAD via structured
      observation. Nevertheless, for a small proportion of children with ASD,
      particularly those whose difficulties may be more subtle, our current
      standardised measures, including structured observation, may not be effective in
      differentiating RAD from ASD.

PMID- 25754457
TI  - Heavy metal mediated immunomodulation of the Indian green frog, Euphlyctis
      hexadactylus (Anura:Ranidae) in urban wetlands.
AB  - Impacts of heavy metal toxicity on the immune system of the Indian green frog,
      Euphlyctis hexadactylus, in Bellanwila Attidiya, an urban wetland polluted with
      high levels of heavy metals, compared to the reference site in Bolgoda, in Sri
      Lanka was investigated. Significantly higher accumulation of selected heavy
      metals, copper (Cu), zinc (Zn), lead (Pb), and cadmium (Cd) were detected by AAS
      in frog liver and gastrocnemius muscle, in the polluted site than in the
      reference site. Non-functional immunotoxicity tests; total WBC, splenocyte and
      bone marrow cell counts, spleen weight/body weight ratio, neutrophil/lymphocyte
      ratio and basal immunoglobulin levels, and phagocytic capacity of peritoneal
      macrophages (immune functional test) were carried out using standard methodology.
      Test parameters recorded significantly lower values for frogs of the polluted
      site compared with their reference site counterparts, indicative of lowered
      immune response of frogs in the former site. In vitro phagocytic assay based on
      NBT dye reduction, measured the stimulation index (SI) of E. hexadactylus blood
      leukocytes, splenocytes and peritoneal macrophages, where SIs of frogs in the
      polluted site were significantly lower. Also, in vitro exposure of frog
      phagocytes to Cu, Zn, Pb and Cd at 10(-2)-10(-10)M, showed immunomodulation i.e.
      low concentrations stimulated phagocytosis while increased concentrations showed
      a trend towards immunosuppression. IC50 values indicated Cd>Zn>Cu>Pb as the
      decreasing order of the potential of phagocytosis inhibition. In conclusion, this
      study clearly demonstrated immunomodulation of E. hexadactylus, stimulated by
      heavy metals. In-vitro studies evidently suggested the use of phagocytosis as a
      biomarker in Ecoimmunotoxicology to detect aquatic heavy metal pollution. 

PMID- 25754458
TI  - Transvaginal prolapse repair with or without the addition of a midurethral sling
      in women with genital prolapse and stress urinary incontinence: a randomised
      trial.
AB  - OBJECTIVE: To compare transvaginal prolapse repair combined with midurethral
      sling (MUS) versus prolapse repair only. DESIGN: Multi-centre randomised trial.
      SETTING: Fourteen teaching hospitals in the Netherlands. POPULATION: Women with
      symptomatic stage two or greater pelvic organ prolapse (POP), and subjective or
      objective stress urinary incontinence (SUI) without prolapse reduction. METHODS:
      Women were randomly assigned to undergo vaginal prolapse repair with or without
      MUS. Analysis was according to intention to treat. MAIN OUTCOME MEASURES: The
      primary outcome at 12 months' follow-up was the absence of urinary incontinence
      (UI) assessed with the Urogenital Distress Inventory and treatment for SUI or
      overactive bladder. Secondary outcomes included complications. RESULTS: One
      hundred and thirty-four women were analysed at 12 months' follow-up (63 in MUS
      and 71 in control group). More women in the MUS group reported the absence of UI
      and SUI; respectively 62% versus 30% UI (relative risk [RR] 2.09; 95% confidence
      interval [CI] 1.39-3.15) and 78% versus 39% SUI (RR 1.97; 95% CI 1.44-2.71).
      Fewer women underwent treatment for postoperative SUI in the MUS group (10%
      versus 37%; RR 0.26; 95% CI 0.11-0.59). In the control group, 12 women (17%)
      underwent MUS after prolapse surgery versus none in the MUS group. Severe
      complications were more common in the MUS group, but the difference was not
      statistically significant (16% versus 6%; RR 2.82; 95% CI 0.93-8.54).
      CONCLUSIONS: Women with prolapse and co-existing SUI are less likely to have SUI
      after transvaginal prolapse repair with MUS compared with prolapse repair only.
      However, only 17% of the women undergoing POP surgery needed additional MUS. A
      well-informed decision balancing risks and benefits of both strategies should be
      tailored to individual women.

PMID- 25754459
TI  - Tracking sesamin synthase gene expression through seed maturity in wild and
      cultivated sesame species--a domestication footprint.
AB  - Sesamin and sesamolin are the major oil-soluble lignans present in sesame seed,
      having a wide range of biological functions beneficial to human health.
      Understanding sesame domestication history using sesamin synthase gene expression
      could enable delineation of the sesame putative progenitor. This report examined
      the functional expression of sesamin synthase (CYP81Q1) during capsule maturation
      (0-40 days after flowering) in three wild Sesamum species and four sesame
      cultivars. Among the cultivated accessions, only S. indicum (CO-1) exhibited
      transcript abundance of sesamin synthase along with high sesamin content similar
      to S. malabaricum, while the other cultivated sesame showed low expression. The
      sesamin synthase expression analysis, coupled with quantification of sesamin
      level, indicates that sesamin synthase was not positively favoured during
      domestication. The sesamin synthase expression pattern and lignan content, along
      with phylogenetic analysis suggested a close relationship of cultivated sesame
      and the wild species S. malabaricum. The high genetic identity between the two
      species S. indicum and S. malabaricum points towards the role of the putative
      progenitor S. malabaricum in sesame breeding programmes to broaden the genetic
      base of sesame cultivars. This study emphasises the need to investigate
      intraspecific and interspecific variation in the primary, secondary and tertiary
      gene pools to develop superior sesame genotypes.

PMID- 25754460
TI  - Boosting translational research on Alzheimer's disease in Europe: The Innovative
      Medicine Initiative AD research platform.

PMID- 25754462
TI  - Topological states in multi-orbital HgTe honeycomb lattices.
AB  - Research on graphene has revealed remarkable phenomena arising in the honeycomb
      lattice. However, the quantum spin Hall effect predicted at the K point could not
      be observed in graphene and other honeycomb structures of light elements due to
      an insufficiently strong spin-orbit coupling. Here we show theoretically that 2D
      honeycomb lattices of HgTe can combine the effects of the honeycomb geometry and
      strong spin-orbit coupling. The conduction bands, experimentally accessible via
      doping, can be described by a tight-binding lattice model as in graphene, but
      including multi-orbital degrees of freedom and spin-orbit coupling. This results
      in very large topological gaps (up to 35 meV) and a flattened band detached from
      the others. Owing to this flat band and the sizable Coulomb interaction,
      honeycomb structures of HgTe constitute a promising platform for the observation
      of a fractional Chern insulator or a fractional quantum spin Hall phase. 

PMID- 25754464
TI  - Where next for hepatitis B and C surveillance?
AB  - Hepatitis B and C infections are responsible for significant burden of disease
      accounting for 1.3 million deaths globally. There is a lack of quality data on
      the burden of disease due to these infections. One approach to informing policy
      makers on trends in hepatitis B and C is through case reporting of diagnosed
      cases. Data on these cases can identify outbreaks of hepatitis and monitor trends
      in acute and chronic infection. The European Centers for Disease Control (ECDC)
      has developed standardized case definitions and a harmonized reporting framework.
      Two articles in this issue summarize the trends in hepatitis B and C infection in
      Europe. The results show considerable variability in reported cases across
      countries, reflecting in part differences in testing practices. Risk factor
      information highlights the continued importance of injecting drug use as a risk
      factor for hepatitis C infection. Hepatitis case reporting provides valuable
      information, and more complete reporting will improve the utility of the data.
      For a comprehensive epidemiologic assessment of the burden of hepatitis, case
      reporting should be complemented by other sources of data, such as serologic and
      behavioural surveys. 

PMID- 25754463
TI  - Salidroside ameliorates insulin resistance through activation of a mitochondria
      associated AMPK/PI3K/Akt/GSK3beta pathway.
AB  - BACKGROUND AND PURPOSE: Recent reports have suggested that salidroside could
      protect cardiomyocytes from oxidative injury and stimulate glucose uptake in
      skeletal muscle cells by activating AMP-activated protein kinase (AMPK). The aim
      of this study was to evaluate the therapeutic effects of salidroside on diabetic
      mice and to explore the underlying mechanisms. EXPERIMENTAL APPROACH: The
      therapeutic effects of salidroside on type 2 diabetes were investigated.
      Increasing doses of salidroside (25, 50 and 100 mg.kg(-1) .day(-1)) were
      administered p.o. to db/db mice for 8 weeks. Biochemical analysis and
      histopathological examinations were conducted to evaluate the therapeutic effects
      of salidroside. Primary cultured mouse hepatocytes were used to further explore
      the underlying mechanisms in vitro. KEY RESULTS: Salidroside dramatically reduced
      blood glucose and serum insulin levels and alleviated insulin resistance.
      Hypolipidaemic effects and amelioration of liver steatosis were observed after
      salidroside administration. In vitro, salidroside dose-dependently induced an
      increase in the phosphorylations of AMPK and PI3K/Akt, as well as glycogen
      synthase kinase 3beta (GSK3beta) in hepatocytes. Furthermore, salidroside
      stimulated AMPK activation was found to suppress the expression of PEPCK and
      glucose-6-phosphatase. Salidroside-induced AMPK activation also resulted in
      phosphorylation of acetyl CoA carboxylase, which can reduce lipid accumulation in
      peripheral tissues. In isolated mitochondria, salidroside inhibited respiratory
      chain complex I and disturbed oxidation/phosphorylation coupling and moderately
      depolarized the mitochondrial membrane potential, resulting in a transient
      increase in the AMP/ATP ratio. CONCLUSIONS AND IMPLICATIONS: Salidroside exerts
      an antidiabetic effect by improving the cellular metabolic flux through the
      activation of a mitochondria-related AMPK/PI3K/Akt/GSK3beta pathway.

PMID- 25754465
TI  - Targeting procaspase-3 with WF-208, a novel PAC-1 derivative, causes selective
      cancer cell apoptosis.
AB  - Caspase-3 is a critical effector caspase in apoptosis cascade, and is often over
      expressed in many cancer tissues. The first synthesized procaspase-3 activator,
      PAC-1, induces cancer cell apoptosis and exhibits antitumour activity in murine
      xenograft models. To identify more potent procaspase-3 activators, a series of
      compounds were designed, synthesized and evaluated for their ability of inducing
      cancer cell death in culture. Among these compounds, WF-208 stood out by its high
      cytotoxicity against procaspase-3 overexpressed HL-60 cells. Compared with PAC-1,
      WF-208 showed higher cytotoxicity in cancer cells and lower toxicity in normal
      cells. The further investigation described herein showed that WF-208 activated
      procaspase-3, degraded IAPs (The Inhibitors of apoptosis proteins) and leaded to
      caspase-3-dependent cell death in tumour cells, which possibly because of the
      zinc-chelating properties. WF-208 also showed greater antitumour activity than
      PAC-1 in murine xenograft model. In conclusion, we have discovered WF-208 as a
      promising procaspase-3 activating compound, with higher activity and higher cell
      selectivity than PAC-1. 

PMID- 25754467
TI  - Diastereoselective carbonyl allylation with simple olefins enabled by palladium
      complex-catalyzed C-H oxidative borylation.
AB  - A highly diastereoselective Pd-catalyzed carbonyl allylation of aldehydes and
      isatins directly using simple acyclic olefins as allylating reagents is
      described. This transformation is actually a sequential process consisting of a
      Pd-catalyzed oxidative allylic C-H borylation and an allylboration of carbonyls
      accelerated by phosphoric acid, wherein a wide scope of olefins could be
      tolerated. The oxidant is revealed to play a key role in the successful
      realization of the allylic C-H activation-based allylation. 

PMID- 25754466
TI  - Migration as an adaptive strategy to climate variability: a study of the Tonga
      speaking people of Southern Zambia.
AB  - There is increasing consensus that the effects of extreme weather conditions in
      the form of drought, flooding and extreme temperature will have increasingly
      devastating impacts on those who depend on climate-sensitive resources and
      ecosystems for their livelihoods. The most affected will be the poor in
      developing countries who have a low adaptive capacity to climate change due to
      high poverty levels. Despite these projections, there are, to date, insufficient
      empirical studies linking the relationship between climate change and migration,
      particularly in the context of southern Africa. Using field-based data collected
      from two study locations in Zambia, this paper examines the complex relationship
      between extreme weather events and population movement. It is envisaged that the
      findings presented in this paper will contribute to current discussions on the
      complex relationship between extreme weather conditions and population movement
      specifically in the context of sub-Saharan Africa and other developing countries.

PMID- 25754468
TI  - Lunge feeding in early marine reptiles and fast evolution of marine tetrapod
      feeding guilds.
AB  - Traditional wisdom holds that biotic recovery from the end-Permian extinction was
      slow and gradual, and was not complete until the Middle Triassic. Here, we report
      that the evolution of marine predator feeding guilds, and their trophic
      structure, proceeded faster. Marine reptile lineages with unique feeding
      adaptations emerged during the Early Triassic (about 248 million years ago),
      including the enigmatic Hupehsuchus that possessed an unusually slender mandible.
      A new specimen of this genus reveals a well-preserved palate and mandible, which
      suggest that it was a rare lunge feeder as also occurs in rorqual whales and
      pelicans. The diversity of feeding strategies among Triassic marine tetrapods
      reached their peak in the Early Triassic, soon after their first appearance in
      the fossil record. The diet of these early marine tetrapods most likely included
      soft-bodied animals that are not preserved as fossils. Early marine tetrapods
      most likely introduced a new trophic mechanism to redistribute nutrients to the
      top 10 m of the sea, where the primary productivity is highest. Therefore, a
      simple recovery to a Permian-like trophic structure does not explain the biotic
      changes seen after the Early Triassic. 

PMID- 25754469
TI  - A tris(triazolate) ligand for a highly active and magnetically recoverable
      palladium catalyst of selective alcohol oxidation using air at atmospheric
      pressure.
AB  - High efficiency and selectivity, easy magnetic recovery and recycling, and use of
      air as the oxidant at atmospheric pressure are major objectives for oxidation
      catalysis in terms of sustainable and green processes. A tris(triazolyl) ligand,
      so far only used in copper-catalyzed alkyne azide cycloadditions, was found to be
      extremely efficient in SiO2 /gamma-Fe2 O3 -immobilized palladium complexes. It
      was characterized by inductively coupled plasma (ICP) analysis, transmission
      electron microscopy (TEM), scanning transmission electron microscopy (STEM),
      energy-dispersive X-ray spectroscopy (EDX), and X-ray photoelectron spectra (XPS)
      and found to fulfill the combined conditions for the selective oxidation of
      alcohols to aldehydes and ketones. 

PMID- 25754470
TI  - The role of uncertainty regarding the results of screening immunoassays in blood
      establishments.
AB  - The risk of uncertain results in infectious agents' tests is recognized in blood
      establishments, being particularly evident during the blood donor selection. The
      current risk-based approaches require risk assessment and "risk-based thinking".
      Accordingly, the blood establishment should consider the effect of uncertainty in
      all the technical decisions taken in a screening laboratory. Since the post
      transfusion safety is one of the blood establishments' goals, the risk of post
      transfusion infection should be evaluated and actions taken to decrease the
      chance of blood donations validation use false negative results. This article
      reviews and discusses the sources of uncertainty of infectious agents' reported
      results in blood establishments. It describes a set of sources of uncertainty
      that should be considered in screening immunoassay's decisions. The infectious
      agents' uncertainty concern is critical for reporting reliable results. 

PMID- 25754471
TI  - Investigating the micromorphological differences of the implant-abutment junction
      and their clinical implications: a pilot study.
AB  - PURPOSE: The aim of this pilot study was to investigate the morphological micro
      features of three commercially available implant-abutment joints, using
      compatible and original prosthetic components. Furthermore, possible correlations
      between the micromorphology and potential functional complications were
      investigated with the use of finite element analysis. MATERIAL AND METHODS: Three
      abutments (one original and two compatibles) were torqued on original Straumann
      RN implants, as according to each of the manufacturer's instructions. The implant
      abutment units were sliced in the microtome and photographed under different
      magnifications (10*-500*) through a scanning electron microscope. Finite element
      analysis models were reconstructed for each of the implant-abutment units using
      the precise measurements from the SEM. Differences in stress, strain and
      deformation for the three different abutments were then calculated using ANSYS
      Workbench v13. RESULTS: Major dimensional differences were identified between all
      studied contact areas of the three units. The tight contact in the implant
      shoulder was similar in all three units, but engagement of the internal
      connection and, in particular, the anti-rotation elements was seriously
      compromised in the compatible abutments. One compatible abutment demonstrated
      compromised engagement of the abutment screw as well. Equivalent stress and
      strain in the FEA were much higher for the compatible abutments. An evaluation of
      the sequence of preload application revealed differences in the pattern of
      deformation between the original and compatible abutments, which can have serious
      clinical implications. CONCLUSION: Compatible abutments can present critical
      morphological differences from the original ones. The differences in the cross
      sectional geometry result in large differences in the overall contact areas, both
      in terms of quality and quantity which could have serious implications for the
      long-term stability of the prosthesis.

PMID- 25754472
TI  - Activation of muscular TrkB by its small molecular agonist 7,8-dihydroxyflavone
      sex-dependently regulates energy metabolism in diet-induced obese mice.
AB  - Chronic activation of brain-derived neurotrophic factor (BDNF) receptor TrkB is a
      potential method to prevent development of obesity, but the short half-life and
      nonbioavailable nature of BDNF hampers validation of the hypothesis. We report
      here that activation of muscular TrkB by the BDNF mimetic, 7,8-dihydroxyflavone
      (7,8-DHF), is sufficient to protect the development of diet-induced obesity in
      female mice. Using in vitro and in vivo models, we found that 7,8-DHF treatment
      enhanced the expression of uncoupling protein 1 (UCP1) and AMP-activated protein
      kinase (AMPK) activity in skeletal muscle, which resulted in increased systemic
      energy expenditure, reduced adiposity, and improved insulin sensitivity in female
      mice fed a high-fat diet. This antiobesity activity of 7,8-DHF is muscular TrkB
      dependent as 7,8-DHF cannot mitigate diet-induced obesity in female muscle
      specific TrkB knockout mice. Hence, our data reveal that chronic activation of
      muscular TrkB is useful in alleviating obesity and its complications.

PMID- 25754473
TI  - Cell-specific RNA aptamer against human CCR5 specifically targets HIV-1
      susceptible cells and inhibits HIV-1 infectivity.
AB  - The C-C chemokine receptor type 5 (CCR5) is a receptor expressed by T cells and
      macrophages that serves as a coreceptor for macrophage-tropic HIV-1. Loss of CCR5
      is associated with resistance to HIV-1. Here, we combine the live-cell-based
      SELEX with high-throughput sequencing technology to generate CCR5 RNA aptamers
      capable of specifically targeting HIV-1 susceptible cells (as small interfering
      RNA [siRNA] delivery agent) and inhibiting HIV-1 infectivity (as antiviral agent)
      via block of the CCR5 required for HIV-1 to enter cells. One of the best
      candidates, G-3, efficiently bound and was internalized into human CCR5
      expressing cells. The G-3 specifically neutralized R5 virus infection in primary
      peripheral blood mononuclear cells, and in vivo generated human CD4(+) T cells
      with a nanomolar inhibitory concentration 50%. G-3 was also capable of
      transferring functional siRNAs to CCR5-expressing cells. Collectively, the cell
      specific, internalizing, CCR5-targeted aptamers and aptamer-siRNA conjugates
      offer promise for overcoming some of the current challenges of drug resistance in
      HIV-1 by providing cell-type- or tissue-specific delivery of various therapeutic
      moieties.

PMID- 25754474
TI  - Islet amyloid-induced cell death and bilayer integrity loss share a molecular
      origin targetable with oligopyridylamide-based alpha-helical mimetics.
AB  - Islet amyloid polypeptide (IAPP) is a hormone cosecreted with insulin. IAPP
      proceeds through a series of conformational changes from random coil to beta
      sheet via transient alpha-helical intermediates. An unknown subset of these
      events are associated with seemingly disparate gains of function, including
      catalysis of self-assembly, membrane penetration, loss of membrane integrity,
      mitochondrial localization, and finally, cytotoxicity, a central component of
      diabetic pathology. A series of small molecule, alpha-helical mimetics,
      oligopyridylamides, was previously shown to target the membrane-bound alpha
      helical oligomeric intermediates of IAPP. In this study, we develop an improved,
      microwave-assisted synthesis of oligopyridylamides. A series of designed
      tripyridylamides demonstrate that lipid-catalyzed self-assembly of IAPP can be
      deliberately targeted. In addition, these molecules affect IAPP-induced leakage
      of synthetic liposomes and cellular toxicity in insulin-secreting cells. The
      tripyridylamides inhibit these processes with identical rank orders of
      effectiveness. This indicates a common molecular basis for the disparate set of
      observed effects of IAPP.

PMID- 25754475
TI  - High-performance hybrid oxide catalyst of manganese and cobalt for low-pressure
      methanol synthesis.
AB  - Carbon dioxide capture and use as a carbon feedstock presents both environmental
      and industrial benefits. Here we report the discovery of a hybrid oxide catalyst
      comprising manganese oxide nanoparticles supported on mesoporous spinel cobalt
      oxide, which catalyses the conversion of carbon dioxide to methanol at high
      yields. In addition, carbon-carbon bond formation is observed through the
      production of ethylene. We document the existence of an active interface between
      cobalt oxide surface layers and manganese oxide nanoparticles by using X-ray
      absorption spectroscopy and electron energy-loss spectroscopy in the scanning
      transmission electron microscopy mode. Through control experiments, we find that
      the catalyst's chemical nature and architecture are the key factors in enabling
      the enhanced methanol synthesis and ethylene production. To demonstrate the
      industrial applicability, the catalyst is also run under high conversion regimes,
      showing its potential as a substitute for current methanol synthesis
      technologies. 

PMID- 25754477
TI  - [Low anterior resection syndrome].
AB  - The most important quality parameters of rectal cancer surgery are oncological
      radicality, postoperative complications, recurrence rate and survival. Rectal
      dysfunction following low anterior resection occurs in up to 25-50% of patients.
      Despite its high frequency, however, it does not receive enough attention. Rectal
      dysfunction after surgery includes frequent bowel movements, urgency, incomplete
      evacuation, incontinence or sexual and urinary dysfunctions. The complex of
      symptoms is collectively referred to as the low anterior resection syndrome -
      LARS. In this review, we discuss the alterations in anorectal physiology after
      low anterior resection, the etiology and risk factors of LARS, different types of
      neorectal reservoir construction, and various options for prevention and
      treatment of LARS. Furthermore, sexual and urinary dysfunction is briefly
      reviewed. KEYWORDS: low anterior resection bowel dysfunction incontinence
      anorectal physiology.

PMID- 25754476
TI  - A computational study of pressure wave reflections in the pulmonary arteries.
AB  - Experiments using wave intensity analysis suggest that the pulmonary circulation
      in sheep and dogs is characterized by negative or open-end type wave reflections,
      that reduce the systolic pressure. Since the pulmonary physiology is similar in
      most mammals, including humans, we test and verify this hypothesis by using a
      subject specific one-dimensional model of the human pulmonary circulation and a
      conventional wave intensity analysis. Using the simulated pressure and velocity,
      we also analyse the performance of the P-U loop and sum of squares techniques for
      estimating the local pulse wave velocity in the pulmonary arteries, and then
      analyse the effects of these methods on linear wave separation in the main
      pulmonary artery. P-U loops are found to provide much better estimates than the
      sum of squares technique at proximal locations, but both techniques accumulate
      progressive error at distal locations away from heart, particularly near
      junctions. The pulse wave velocity estimated using the sum of squares method also
      gives rise to an artificial early systolic backward compression wave. Finally, we
      study the influence of three types of pulmonary hypertension viz. pulmonary
      arterial hypertension, chronic thromboembolic pulmonary hypertension and
      pulmonary hypertension associated with hypoxic lung disease. Simulating these
      conditions by changing the relevant parameters in the model and then applying the
      wave intensity analysis, we observe that for each group the early systolic
      backward decompression wave reflected from proximal junctions is maintained,
      whilst the initial forward compression and the late systolic backward compression
      waves amplify with increasing pathology and contribute significantly to increases
      in systolic pressure. 

PMID- 25754478
TI  - [The role of surgical embolectomy and extracorporeal membrane oxygen therapy in
      the treatment of massive pulmonary embolism - a review].
AB  - Acute massive pulmonary embolism remains potentially lethal with mortality
      varying between 2553%. In the thrombolytic era, surgical pulmonary embolectomy is
      deemed as a rescue approach for patients with absolute contraindication of
      thrombolysis or its failure. However, close interdisciplinary cooperation,
      meticulous choice of optimal reperfusion strategy, standardization of surgical
      approach, and mainly the inclusion of mechanical circulatory support into the
      treatment algorithm have led to a drop in in-hospital mortality below 10% in the
      last 10 years. Nevertheless, cardiac arrest and refractory cardiogenic shock
      still remain independent risk factors of death with mortality exceeding 70%.
      Extracorporeal membrane oxygen therapy provides rapid circulatory support, end
      organ perfusion and oxygenation which are essential for right-sided obstruction
      haemodynamic. Subsequently, optimal reperfusion strategy can be chosen or
      patients may be transported for it. The review highlights the contemporary role
      of surgical pulmonary embolectomy and extracorporeal membrane oxygen therapy in
      the treatment algorithm for acute massive pulmonary embolism, summarising current
      perspectives on the indications and contraindications for these treatment
      strategies and their results.Key words: massive pulmonary embolism - surgical
      pulmonary embolectomy - extracorporeal membrane oxygen therapy. 

PMID- 25754479
TI  - [Surgical repair of recurrent pectus excavatum in adults and adolescents].
AB  - INTRODUCTION: Recurrent pectus excavatum is the most serious late complication
      after primary repair. Redo open repair (Highly Modified Ravitch Repair, HMRR) or
      minimally invasive repair of pectus excavatum (MIRPE) are usually performed in
      indicated cases. This paper focuses on the evaluation of available redo surgical
      techniques in adult and adolescent patients with recurrent pectus excavatum.
      METHODS: 126 operative corrections, predominantly in adult patients, were
      performed by the authors between June 2006 and October 2014. HMRR was the method
      of choice in 51 cases, and MIRPE in 75 cases. Recurrent pectus excavatum was the
      indication in 12 repair procedures (9.5%) in 11 patients. Prior repairs included
      HMRR in 10 patients and MIRPE in one case. Both HMRR and MIRPE were indicated as
      redo procedure in six cases. The median age in the redo group was 23.5 (1744)
      years and the median interval between the primary correction and the redo
      procedure was 9.5 (231) years. The male to female ratio was 3:1. RESULTS: The use
      of MIRPE resulted in shorter operation time (120 vs. 172 min). There was no
      difference in the length of postoperative hospitalisation. Three complications
      (50%) were recorded in the HMRR group (wound seroma, intrapericardial bar
      migration with hemopericardium, displaced rectus abdominis muscle) and one
      (16.7%) occurred in the MIRPE group (symptomatic fluidothorax). CONCLUSION:
      Despite our limited experience with both techniques in the treatment of recurrent
      pectus excavatum we believe that MIRPE should be regarded as a safe and effective
      technique for the redo repair in adolescent and adult patients.Key words: HMRR -
      MIRPE recurrent pectus excavatum.

PMID- 25754480
TI  - [Avoidance of axillary lymph node dissection in breast cancer patients with
      metastatic sentinel node - a pilot study].
AB  - INTRODUCTION: Axillary lymph node dissection (ALND) is a standard procedure for
      locoregional control in metastatic sentinel lymph nodes (SN). A number of studies
      have provided evidence that avoiding ALND does not worsen the general prognosis.
      METHODS: A group of 249 female patients with sentinel lymph node biopsy was
      analysed retrospectively for a 3-year period. The patients were divided into two
      groups - with non-metastatic SN and with metastatic SN. In the metastatic SN
      group, the patients were further divided into a group with ALND and a group
      without ALND, and additional lymph nodes (non-sentinel) in ALND and oncological
      treatment were evaluated. The goal was to find out whether ALND and oncological
      treatment affect the disease-free interval (DFI) and overall survival (OS) in the
      group of patients with metastatic SN and to compare the results with the control
      group. The histopathology and biology of the primary tumour, its size and the
      number of metastatic SN were subsequently evaluated as the factors that may be
      useful for predicting metastatic non-sentinel lymph node positivity. RESULTS:
      There was a high risk of metastatic non-sentinel lymph nodes in the cases of
      metastatic SN (63%). Addition of ALND does not prolong either DFI or DFS without
      post-operative radiotherapy and systemic oncological treatment, both of which can
      provide a comparable length of DFI as well as DFS without ALND. Patients with
      metastatic SN with and without ALND had a DFI of 70 and 72 months, respectively,
      and a 5-year survival of 84% and 80%, respectively. Tumours over 2 cm, tumours
      with high proliferative activity and a high grade can be regarded as predictors
      of metastatic non-sentinel lymph nodes. CONCLUSION: In a small patient group it
      has been demonstrated that the avoidance of ALND in 1 or 2 metastatic SN,
      regardless of the prognostic factors, does not affect either DFI or DFS if
      adjuvant oncological treatment is administered. High-grade tumours, tumours with
      high proliferative activity and tumours larger than 2 cm carry a significantly
      higher risk of metastatic non-sentinel lymph nodes. Nowadays, the avoidance of
      ALND in metastatic SN is not a lege artis procedure; further large studies are
      needed to create scientific guidelines.Key words: metastatic sentinel lymph node 
      avoidance of axillary dissection - breast cancer.

PMID- 25754481
TI  - [Failed preoperative lymphoscintigraphy for sentinel lymph node biopsy in breast
      cancer, possible causes and implications for the surgery - the analysis of 3014
      procedures].
AB  - INTRODUCTION: The aim of the study was to review the cases of sentinel lymph node
      biopsy for breast cancer in which preoperative lymphoscintigraphy had shown no
      axillary hot spot; to assess the frequency of failed examinations and possible
      causes of the failure; to analyze subsequent surgical procedures and hence to
      provide a general recommendation on what to do in such a situation. METHODS: A
      retrospective overview of 3014 lymphoscintigraphy examinations at the Masaryk
      Memorial Cancer Institute from 2001 to 2011 with a more detailed analysis of the
      cases with axillary hot spot visualization failure. RESULTS: The axillary hot
      spot was not shown in 71 examinations (2.4%). The frequency of failed
      lymphoscintigraphy during the time period did not change substantially. The
      possible risk factors of failed lymphoscintigraphy include: previous surgery on
      the breast or the axilla, obturation of the lymphatic drainage with the cancer,
      and the absence of the tracer injection site massage. The most common surgical
      procedures to respond to a failed examination were: the application of patent
      blue and surgical exploration of the axilla, no axillary surgery, or axillary
      dissection. CONCLUSION: When repeated scanning with the gamma camera through the
      first several hours is performed, the frequency of failed lymphoscintigraphy
      procedures remains very low (2.4%). If there is no axillary hot spot shown,
      patent blue is to be injected and the axilla should be surgically explored. This
      solution will be successful in most patients. If the sentinel lymph node cannot
      be detected even using the combined method, the surgical procedure needs to be
      selected with regard to the individual clinical context.Key words: breast cancer 
      sentinel lymph node - sentinel lymph node biopsy - lymphoscintigraphy - failed
      detection.

PMID- 25754482
TI  - [Delayed liver hematoma development following deceleration injury].
AB  - Our report presents the case of a young woman who suffered liver trauma after
      electrical current injury and ensuing fall from an electricity pylon. The
      resulting intrahepatic hematoma manifested after a time interval of 48 hours
      following the injury, with initially negative CT scan.Key words: liver hematoma
      electrical current - polytrauma burns. 

PMID- 25754483
TI  - [The first lung re-transplantation in the Czech Republic].
AB  - Nowadays, lung re-transplantation is an acceptable method of treatment in
      patients with graft failure after lung transplantation. During the 15-year
      duration of the lung transplant program in the Czech Republic, the first re
      transplantation was performed on 1. 8. 2012. This article presents the case
      report of a female patient with lymphangioleiomyomatosis who underwent single
      lung transplantation on the left side on 4. 10. 1998. Over 12 years, based on
      bronchiolitis obliterans syndrome, she developed chronic respiratory
      insufficiency again. The patient was re-listed on the waiting list and on 1. 8.
      2012, successful single-lung transplantation on the right side was performed.Key
      words: lung re-transplantation bronchiolitis obliterans syndrome organ
      allocation. 

PMID- 25754484
TI  - Erratum to: The neostriatum: two entities, one structure?

PMID- 25754485
TI  - Presence of antibodies against Leptospira serovars in Chaetophractus villosus
      (Mammalia, Dasypodidae), La Pampa province, Argentina.
AB  - Leptospirosis is a zoonosis of worldwide distribution. The aim of this study was
      to examine the presence of antibodies against 21 Leptospira reactive serovars in
      Chaetophractus villosus in La Pampa province, Argentina, using the microscopic
      agglutination test (MAT). Pathologic changes compatible with leptospirosis and in
      situ detection of the agent by immunohistochemistry were studied in 24 and 3
      individuals respectively. Only 35/150 (23.3%) serum samples had antibodies
      against Leptospira sp. Six percent of the samples reacted with serovar Canicola,
      4.7% with serovar Castellonis, 1.3% with serovar Icterohemorrhagieae and 0.7%
      with serovar Hardjo. Sixteen (10.6%) serum samples agglutinated with Castellonis
      Icterohemorrhagiae and Canicola-Castellonis serovars, both with 4.7%, and
      Canicola-Hardjo and Castellonis-Canicola-Icterohemorrhagiae both with 0.6%.
      Fourteen animals had variable degrees of lesions, which were more severe in
      animals with higher serological titers (3200), and Leptospira sp. was detected in
      3 animals by immunohistochemistry. These results represent the first record of
      the presence of Leptospira in C. villosus in La Pampa. 

PMID- 25754486
TI  - [Onychomycosis for Curvularia lunata var. aeria: presentation of a clinical
      case].
AB  - We here report a clinical case of a female patient presenting with a three-month
      history of a white onychodystrophic lesion of both hallux. The infection was due
      to a mold, identified as Curvularia lunata var aeria. The Curvularia gender is
      related to the production of phaeohyphomycosis, Curvularia lunata cause
      onychomycosis occasionally. The patient was treated with itraconazole 200mg/day,
      during six month with complete remission of the lesions. In conclusion, it is
      important to consider these fungi as causative agent of nail mycosis since the
      initial site of infection may be a pathway for systemic dissemination in
      inmunocompromised patients. 

PMID- 25754487
TI  - [Drivers for the emergence of biological hazards in foods].

PMID- 25754488
TI  - In-hospital mortality risk prediction after percutaneous coronary interventions:
      Validating and updating the Toronto score in Brazil.
AB  - OBJECTIVES: We aimed to assess the accuracy of the simple, contemporary and well
      designed Toronto PCI mortality risk score in ICP-BR registry, the first Brazilian
      PCI multicenter registry with follow-up information. BACKGROUND: Estimating
      percutaneous coronary intervention (PCI) mortality risk by a clinical prediction
      model is imperative to help physicians, patients and family members make informed
      clinical decisions and optimize participation in the consent process, reducing
      anxiety and improving quality of care. At a healthcare system level, risk
      prediction scores are essential to measure and benchmark performance. METHODS:
      Between 2009 and 2013, a cohort of 4,806 patients from the ICP-BR registry,
      treated with PCI in eight tertiary referral medical centers, was included in the
      analysis. This population was compared to 10,694 patients of the derivation
      dataset from the Toronto study. To assess predictive performance, an update of
      the model was performed by three different methods, which were compared by
      discrimination, calculating the area under the receiver operating characteristic
      curve (AUC), and by calibration, assessed through Hosmer-Lemeshow (H-L) test and
      graphical analysis. RESULTS: Death occurred in 2.6% of patients in the ICP-BR
      registry and in 1.3% in the Toronto cohort. The median age was 64 and 63 years,
      23.8 and 32.8% were female, 28.6 and 32.3% were diabetics, respectively. Through
      recalibration of intercept and slope (AUC = 0.8790; H-L P value = 0.3132), we
      achieved a well-calibrated and well-discriminative model. CONCLUSIONS: After
      updating to our dataset, we demonstrated that the Toronto PCI in-hospital
      mortality risk score performed well in Brazilian hospitals.

PMID- 25754489
TI  - Synthesis, anticonvulsant activity and molecular modeling study of some new
      hydrazinecarbothioamide, benzenesulfonohydrazide, and phenacylacetohydrazide
      analogues of 4(3H)-quinazolinone.
AB  - A new series of quinazoline analogues was designed and synthesized to get the
      target compounds 18-21, 30-41, 46-53, and 57-76. The Obtained compounds were
      evaluated for their anticonvulsant activity using PTZ and picrotoxin convulsive
      models. Compounds 47, 63, 68 and 73 proved to be the most active compounds in
      this study with a remarkable 100% protection against PTZ induced convulsions.
      Compounds 47, 63, 68 and 73 proved to be 10, 4, 4, and 5 fold more active,
      respectively than the used positive control sodium valproate. Structure activity
      correlation concluded valuable pharmacophoric information which confirmed by
      molecular modeling studies. Molecular docking study of 68 suggested its agonistic
      behavior toward GABAA receptor. The studied quinazoline analogues could be
      considered as useful templates for future development and further derivatization.

PMID- 25754490
TI  - trans-3,4-Disubstituted pyrrolidines as inhibitors of the human aspartyl protease
      renin. Part II: prime site exploration using an oxygen linker.
AB  - Inhibition of the aspartyl protease renin is considered as an efficient approach
      for treating hypertension. Lately, we described the discovery of a novel class of
      direct renin inhibitors which comprised a pyrrolidine scaffold (e.g., 2). Based
      on the X-ray structure of the lead compound 2 bound to renin we predicted that
      optimization of binding interactions to the prime site could offer an opportunity
      to further expand the scope of this chemotype. Pyrrolidine-based inhibitors were
      synthesized in which the prime site moieties are linked to the pyrrolidine core
      through an oxygen atom, resulting in an ether or a carbamate linker subseries.
      Especially the carbamate derivatives showed a pronounced increase in in vitro
      potency compared to 2. Here we report the structure-activity relationship of both
      subclasses and demonstrate blood pressure lowering effects for an advanced
      prototype in a hypertensive double-transgenic rat model after oral dosing. 

PMID- 25754491
TI  - 8-(3-chloro-4-methoxybenzyl)-8H-pyrido[2,3-d]pyrimidin-7-one derivatives as
      potent and selective phosphodiesterase 5 inhibitors.
AB  - A novel series of highly selective phosphodiesterase 5 (PDE5) inhibitors was
      found. 8H-Pyrido[2,3-d]pyrimidin-7-one derivatives bearing an (S)-2
      (hydroxymethyl)pyrrolidin-1-yl group at the 2-position and a 3-chloro-4
      methoxybenzyl group at the 8-position exhibited potent PDE5 inhibitory activities
      and high PDE5 selectivity over PDE6. Among the synthesized compounds, the 5
      methyl analogue (5b) showed the most potent relaxant effect on isolated rabbit
      corpus cavernosum with an EC30 value of 0.85 nM.

PMID- 25754492
TI  - Synthesis and antitubercular evaluation of 4-carbonyl piperazine substituted 1,3
      benzothiazin-4-one derivatives.
AB  - Tuberculosis (TB) remains a major human health problem. New therapeutic
      antitubercular agents are urgent needed to control the global tuberculosis
      pandemic. We synthesized a new series of 4-carbonyl piperazine substituted 1,3
      benzothiazin-4-one derivatives and evaluated their anti-mycobacterial activities
      against Mycobacterium tuberculosis H37Ra as well as their druggabilities. The
      results showed that most of these derivatives, especially the compounds with
      simple alkyl side chains, exhibited good antitubercular activities and favorable
      aqueous solubilities with no obvious cytotoxicity. It suggested that the 4
      carbonyl piperazine substituents in benzothiazinone scaffold were well tolerated,
      in which the compound 8h, with an antitubercular activity of MIC 0.008 MUM,
      exhibited an excellent aqueous solubility of 104 MUg/mL, which was 100-fold
      better than the potent DprE1 inhibitor Comp.1 (BTZ038), also more soluble than
      PBTZ169.

PMID- 25754493
TI  - Synthesis and antimicrobial activity of novel benzoxazine sulfonamide
      derivatives.
AB  - A new series of benzoxazine-6-sulfonamide derivatives were synthesized in
      excellent yields and the resulting compounds were evaluated for their
      antimicrobial activities. All the synthesized compounds were assessed for their
      antibacterial and antifungal activities. Among them 1a, 1b, 1c, 1e, 1h, 2c, 2d,
      2e, 2g, 2h, 2i, 2j, 2k and 2l showed low inhibitory concentration (MIC of 31.25
      and 62.5 MUg/mL) against Gram-positive bacteria, Gram-negative bacteria and
      fungi, which are comparable to the inhibitory effect of standard drugs.

PMID- 25754494
TI  - Determination of the active stereoisomer of the MEP pathway-targeting
      antimalarial agent MMV008138, and initial structure-activity studies.
AB  - Compounds that target isoprenoid biosynthesis in Plasmodium falciparum could be a
      welcome addition to malaria chemotherapy, since the methylerythritol phosphate
      (MEP) pathway used by the parasite is not present in humans. We previously
      reported that MMV008138 targets the apicoplast of P. falciparum and that its
      target in the MEP pathway differs from that of Fosmidomycin. In this Letter, we
      determine that the active stereoisomer of MMV008138 is 4a, which is (1R,3S)
      configured. 2',4'-Disubstitution of the D ring was also found to be crucial for
      inhibition of the parasite growth. Limited variation of the C3-carboxylic acid
      substituent was carried out, and methylamide derivative 8a was found to be more
      potent than 4a; other amides, acylhydrazines, and esters were less potent.
      Finally, lead compounds 4a, 4e, 4f, 4h, 8a, and 8e did not inhibit growth of
      Escherichia coli, suggesting that protozoan-selective inhibition of the MEP
      pathway of P. falciparum can be achieved. 

PMID- 25754495
TI  - The discovery of potent agonists for GPR88, an orphan GPCR, for the potential
      treatment of CNS disorders.
AB  - Modulating GPR88 activity is suggested to have therapeutic utility in the
      treatment of CNS disorders, such as schizophrenia. This Letter will describe the
      discovery and SAR development of a class of potent GPR88 agonists. 

PMID- 25754496
TI  - Fracture Strength of Implant-Supported Ceramic Crowns with Customized Zirconia
      Abutments: Screw Retained vs. Cement Retained.
AB  - PURPOSE: To compare the fracture resistance before and after cyclic fatigue
      assays of ceramic crowns with customized zirconia abutments when screw retained
      and cemented onto implants. MATERIALS AND METHODS: The sample of this study
      consisted of 40 ceramic crowns with zirconia infrastructure fixed onto external
      hexagonal implants. The crowns were distributed into two groups (n = 20): Screw
      retained and cemented crowns. Half the crowns of each group (n = 10) underwent
      compression until fracture and the other half (n = 10) underwent cyclic fatigue
      and subsequent compression until fracture. The cyclic fatigue test was carried
      out using an electromechanical fatigue device (loads from 0 to 100 N, 2 Hz
      frequency, in distilled water, at 37  degrees C for a period of 1 million
      cycles). The compression test was carried out using a universal testing machine
      with a 0.5 mm/min speed and 5 KN load cell. After fracture, the crowns were
      classified according to the type of fracture. Student's t test (p < 0.05) was
      used for statistical analysis. RESULTS: The cyclic fatigue altered neither the
      mean fracture resistance of the screw-retained crowns (before = 1068.31 N, after
      = 891.49 N; p > 0.05) nor that of the cemented crowns (before = 2117.78 N; after
      = 2094.81 N; p > 0.05); however, the mean fracture resistance of the cemented
      crowns was higher than that of the screw-retained crowns both before (p < 0.001)
      and after (p < 0.001) the cyclic fatigue. Fractures occurred most frequently in
      the ceramic veneer, followed by fracture of some of the copings. CONCLUSION: The
      ceramic crowns cemented onto the customized zirconia abutments offered greater
      fracture resistance than ceramic crowns with customized zirconia abutments screw
      retained onto implants. The cyclic fatigue did not seem to influence the fracture
      resistance of these crowns, whether cemented or screw retained onto implants.
      Fracture of the veneering ceramic was the predominant failure in this study.

PMID- 25754497
TI  - Superficial fibrin thrombi ... and other findings: a review of the histopathology
      of human scabietic infections.
AB  - BACKGROUND: Cutaneous infection with the mite Sarcoptes scabiei var. hominis is
      associated with epidermal and dermal changes. After noting superficial fibrin
      thrombi in two biopsies with scabies mites, we comprehensively reviewed the
      histopathologic findings in scabietic infections to determine the frequency of
      this finding. METHODS: Twenty five biopsies of scabies infection were retrieved
      from the archives of our institution; only cases containing scabietic mite parts
      or scybala were included. The microscopic features were documented. RESULTS:
      Nearly half (40%) of the cases showed fibrin thrombi within vessels of the
      superficial dermis. Other frequent findings included dermal eosinophils (88% of
      cases), epidermal spongiosis (76% of cases), lymphocyte atypia (64%), a
      superficial and deep infiltrate (52% of cases), dermal neutrophils (52%) and
      endothelial cell swelling (52%). Half of the cases contained polarizable mite
      elements. Less commonly encountered features included extravasated erythrocytes
      (44%), dermal edema (32%), pink 'pigtails'(28%), intraepidermal pustules (24%),
      plasma cells (20%) and vasculitis (4%). CONCLUSIONS: The pathologic
      characteristics of scabietic infection are wide-ranging. Spongiosis, superficial
      and deep inflammation, and dermal eosinophils and neutrophils are seen in the
      majority of cases. Superficial fibrin thrombi are not uncommon in scabietic
      infection, and may provide a helpful diagnostic clue when mites are not visible
      on initial sections.

PMID- 25754498
TI  - Computed tomography and magnetic resonance imaging of thoracic chordoma in a
      Bengal tiger (Panthera tigris tigris).
AB  - A Bengal tiger was presented for evaluation of weakness, ataxia and inappetance.
      Computed tomography (CT) and magnetic resonance imaging (MRI) revealed a mass
      extending from the T7-8 vertebral body to the left rib and compressing the spinal
      cord. On CT, the bone destruction and sequestrum were shown. On MRI, the
      multilobulated mass appeared hypo- to isointense in T1-weighted and hyperintense
      in T2-weighted images. The tiger died after imaging, most likely from renal
      failure. Chordoma without metastasis was diagnosed on necropsy. The imaging
      characteristics were similar to those found in chordoma in humans. This report
      describes the use of CT and MRI in an exotic species. 

PMID- 25754500
TI  - Incidence of malignant mesothelioma of the pleura in Quebec and Canada from 1984
      to 2007, and projections from 2008 to 2032.
AB  - BACKGROUND: Continuous increase in male incidence of malignant mesothelioma of
      the pleura (MMP) despite the drop of asbestos production since 1980 in Quebec
      motivated this study aiming to assess when the rates of MMP will decline.
      METHODS: Age-standardized rates and trends were estimated over the 1984-2007
      period by sex for Quebec versus "Canada-excluding-Quebec" (Can-Qc). An age-cohort
      regression was used to make projections for 2008-2032. RESULTS: Average rates of
      MMP in Quebec men and women were significantly higher than in Can-Qc. Projected
      rates peak between 2003 and 2012 in all four study populations and decline
      thereafter. CONCLUSION: The higher MMP rates and observed/projected time patterns
      in Quebec men are consistent with past asbestos production and occupational
      exposures. The excess in Quebec women may also be explained by domestic and, for
      some, by neighborhood exposures. To pursue the decrease in MMP rates beyond 2032,
      efforts to reduce asbestos exposure should be maintained.

PMID- 25754499
TI  - Schema-conformant memories are preferentially consolidated during REM sleep.
AB  - Memory consolidation is most commonly described by the standard model, which
      proposes an initial binding role for the hippocampus which diminishes over time
      as intracortical connections are strengthened. Recent evidence suggests that slow
      wave sleep (SWS) plays an essential role in this process. Existing animal and
      human studies have suggested that memories which fit tightly into an existing
      knowledge framework or schema might use an alternative consolidation route in
      which the medial prefrontal cortex takes on the binding role. In this study we
      sought to investigate the role of sleep in this process using a novel melodic
      memory task. Participants were asked to remember 32 melodies, half of which
      conformed to a tonal schema present in all enculturated listeners, and half of
      which did not fit with this schema. After a 24-h consolidation interval,
      participants were asked to remember a further 32 melodies, before being given a
      recognition test in which melodies from both sessions were presented alongside
      some previously unheard foils. Participants remembered schema-conformant melodies
      better than non-conformant ones. This was much more strongly the case for
      consolidated melodies, suggesting that consolidation over a 24-h period
      preferentially consolidated schema-conformant items. Overnight sleep was
      monitored between the sessions, and the extent of the consolidation benefit for
      schema-conformant items was associated with both the amount of REM sleep obtained
      and EEG theta power in frontal and central regions during REM sleep. Overall our
      data suggest that REM sleep plays a crucial role in the rapid consolidation of
      schema-conformant items. This finding is consistent with previous results from
      animal studies and the SLIMM model of Van Kesteren, Ruiter, Fernandez, and Henson
      (2012), and suggest that REM sleep, rather than SWS, may be involved in an
      alternative pathway of consolidation for schema-conformant memories. 

PMID- 25754501
TI  - Serum angiopoietin-2 is associated with angiopathy in type 2 diabetes mellitus.
AB  - PURPOSE: The aim of the present study was to investigate the association of serum
      levels of angiopoietin-1 (Ang-1) and angiopoietin-2 (Ang-2) with angiopathy in
      type 2 diabetes mellitus (T2DM). METHODS: The group studied comprised of 120
      patients with T2DM (68 males and 52 females), included macroangiopathy
      complications, microvascular disease and diabetic without vascular disease. The
      control group consisted of 50 healthy blood donors. Ang-1, Ang-2, fasting plasma
      glucose (FBG), fasting insulin (FINS) and HbA1c were assessed. RESULTS: The serum
      Ang-2 levels of T2DM patients with angiopathy were found to be significantly
      higher compared to patients without angiopathy. Ang-2 levels were significantly
      positively correlated with homeostasis model assessment for insulin resistance
      (HOMA-IR) and glycosylated hemoglobin A1c (HbA1c) (r=0.577 and 0.504,
      respectively, P<0.01). In contrast, there was no significant correlation between
      Ang-1 levels and HOMA-IR (P>0.05). In multivariable logistic regression analysis,
      Ang-2 levels (P=0.02) were found to be independently associated with patients
      with T2DM angiopathy. CONCLUSIONS: An association between the Ang-2 and T2DM with
      vascular complications was found.

PMID- 25754502
TI  - Functional mechanisms for type 2 diabetes-associated genetic variants.
AB  - AIMS: Type 2 diabetes (T2D) is a complex endocrine and metabolic disorder,
      characterized by hyperglycemia due to insulin resistance and relative lack of
      insulin. Several recent studies have identified a large number of genetic loci
      associated with T2D without exploring functional mechanisms underlying the
      associations. This study established integrative analyses to detect the
      functional mechanisms for T2D-related associations. METHODS: Based on the public
      available datasets and resources, this study performed integrative analyses (gene
      relationships among implicated loci (GRAIL), expression quantitative trait loci
      (eQTL) analysis, differential gene expression analysis and functional prediction
      analysis) to detect the molecular functional mechanisms underlying the
      associations. RESULTS: Two single nucleotide polymorphisms (SNPs) (rs7593730,
      rs2439312) have been found to act as cis-effect regulators of two corresponding
      eQTL genes (RBMS1, NRG1) among 252 selected (P<E-4) genetic associations that
      were archived in the public databases. These two non-HLA genes were also
      differentially expressed in T2D-related cell groups. The two SNPs were predicted
      as regulatory sites by utilizing online prediction tools. CONCLUSIONS: This study
      detected potential regulatory mechanisms underlying the associations between T2D
      and two identified SNPs. Integrative analysis can be used to provide suggestive
      clues for the molecular functional mechanisms in T2D.

PMID- 25754503
TI  - Fronto-insula network activity explains emotional dysfunctions in juvenile
      myoclonic epilepsy: combined evidence from pupillometry and fMRI.
AB  - Emotional instability, difficulties in social adjustment, and disinhibited
      behavior are the most common symptoms of the psychiatric comorbidities in
      juvenile myoclonic epilepsy (JME). This psychopathology has been associated with
      dysfunctions of mesial-frontal brain circuits. The present work is a first direct
      test of this link and adapted a paradigm for probing frontal circuits during
      empathy for pain. Neural and psychophysiological parameters of pain empathy were
      assessed by combining functional magnetic resonance imaging (fMRI) with
      simultaneous pupillometry in 15 JME patients and 15 matched healthy controls. In
      JME patients, we observed reduced neural activation of the anterior cingulate
      cortex (ACC), the anterior insula (AI), and the ventrolateral prefrontal cortex
      (VLPFC). This modulation was paralleled by reduced pupil dilation during empathy
      for pain in patients. At the same time, pupil dilation was positively related to
      neural activity of the ACC, AI, and VLPFC. In JME patients, the ACC additionally
      showed reduced functional connectivity with the primary and secondary
      somatosensory cortex, areas fundamentally implicated in processing the somatic
      cause of another's pain. Our results provide first evidence that alterations of
      mesial-frontal circuits directly affect psychosocial functioning in JME patients
      and draw a link of pupil dynamics with brain activity during emotional
      processing. The findings of reduced pain empathy related activation of the ACC
      and AI and aberrant functional integration of the ACC with somatosensory cortex
      areas provide further evidence for this network's role in social behavior and
      helps explaining the JME psychopathology and patients' difficulties in social
      adjustment. 

PMID- 25754504
TI  - Reevaluation of the CLV3-receptor interaction in the shoot apical meristem:
      dissection of the CLV3 signaling pathway from a direct ligand-binding point of
      view.
AB  - The CLAVATA signaling pathway is a key component of the network that controls
      stem cell renewal and differentiation in Arabidopsis thaliana. CLAVATA3 (CLV3) is
      a post-translationally arabinosylated secreted peptide signal that regulates
      WUSHEL (WUS) transcription to affect the balance of stem cell differentiation and
      proliferation in the shoot apical meristem (SAM). Known membrane-localized
      receptors involved in the perception of CLV3 signaling include CLV1, the
      CLV2/CORYNE (CRN) complex and RPK2. The CLV3 peptide can directly bind to CLV1;
      however, it is unclear whether the CLV3 peptide directly binds to CLV2 or RPK2.
      In this study, we re-evaluated the direct interaction between CLV3 and its
      receptors by photoaffinity labeling with photoactivatable arabinosylated CLV3. We
      showed that CLV2 and RPK2 exhibited no direct binding to the CLV3 peptide.
      Further analysis showed that the receptor kinase BAM1 directly binds the CLV3
      peptide. A loss-of-function clv1 bam1 double mutant exhibited a large number of
      stem cells that accumulated in the SAM and was insensitive to exogenous treatment
      with the arabinosylated CLV3 peptide. WUS gene transcripts were up-regulated, and
      the region of WUS expression was enlarged at the SAM in the clv1 bam1 double
      mutant. These results indicate that CLV1 and BAM1 are direct receptors that are
      sufficient to affect the regulatory network controlling stem cell number in the
      SAM. In contrast, the CLV2/CRN complex and RPK2 are not involved in direct ligand
      interactions but may act as co-receptors. 

PMID- 25754505
TI  - Stand alone totally endoscopic epimyocardial ablation in patients with persistent
      atrial fibrillation and significant atrial dilatation.
AB  - BACKGROUND: To analyze safety and efficacy of surgical totally endoscopic
      epimyocardial ablation in patients (pts) turned down for interventional catheter
      therapy due to long-standing persistent atrial fibrillation (pAF) combined with
      significant atrial dilatation (> 5 cm). METHODS: Since December 2010, 15 pts were
      referred for surgical ablation due to persistent AF combined with biatrial
      dilatation (left atrium [LA] 5.0 +/- 0.6 cm). Mean age was 52 +/- 6 years, body
      mass index (BMI) 38 +/- 6, duration of AF 2.8 +/- 1.2 years, left ventricular end
      diastolic diameter (LVEDD) 5.8 cm +/- 0.6 cm. Ablation was performed via a
      bilateral endoscopic approach using bipolar RF energy application. Monitoring was
      achieved by an event recorder (Reveal XT Medtronic, Inc., Minneapolis, MN, USA)
      or repeated 24-hours Holter electrocardiogram. RESULTS: All pts successfully
      received bilateral pulmonary vein isolation + box lesion + trigonal lesion + left
      atrial appendage resection. Mean duration of procedure was 235 +/- 70 minutes.
      There was no intraoperative complication; however, one patient had persistent
      left phrenic nerve palsy. Mean hospital stay was 4 +/- 2 days, mean follow-up
      time was 21 +/- 11 months. Incidence of sinus rhythm (SR) was 67, 73, and 80% at
      discharge, three months, and 12 months follow-up. Mean LA diameter was reduced
      from 58.1 mm +/- 6.0 mm preoperative to 49.7 mm +/- 5.4 mm (p = 0.004) at 12
      months follow-up. Incidence of SR was 86% at latest follow-up (mean time 21
      months). All pts currently in SR (13/15 = 86%) are of class I or III
      antiarrhythmic drugs. CONCLUSION: Totally endoscopic left atrial ablation
      including left atrial resection can safely be performed. It achieved excellent
      rates of SR restoration in patients with long-standing persistent AF combined
      with significant atrial dilatation.

PMID- 25754506
TI  - Brief communication of assessment of clinical practice regarding pharmacological
      treatment of epilepsy: a survey of neurologists in Republic of Macedonia.
AB  - A questionnaire of 15 items was developed in order to evaluate clinical practice
      regarding pharmacological treatment of epilepsy among adult neurologists in R.
      Macedonia. It was mailed to 30 practising neurologists, 24 answered (80%). Half
      of them administer AED after a first unprovoked seizure considering EEG and MRI,
      while others usually wait for a second one before introducing treatment.
      Discontinuation of treatment should be individualized. Carbamazepine and
      lamotrigine are the most frequently prescribed first-line drugs for partial
      seizures; second choices include a number of older and new generation AEDs. For
      generalized tonic-clonic seizures, absences, myoclonic, mixed or undetermined
      seizures, valproate is by far the most commonly used AED. The survey showed that
      prescription patterns are in accordance with current evidence about the spectrum
      of efficacy of individual AEDs in different types of seizures. Yet some results
      are a cause of concern and continuous education of the neurological community on
      AED treatment of epilepsy is needed.

PMID- 25754507
TI  - Retinal complications in diabetes mellitus: importance of screening and
      management.
AB  - INTRODUCTION: Diabetic retinal complications are the most common cause of reduced
      visual acuity in persons aged 25 to 75 years. However, vision loss can be
      prevented or delayed if the changes are seen on time. AIM: By analyzing
      literature data to create an algorithm for careful follow-up of diabetic
      patients, which would prevent progression of the changes and development of
      conditions leading to blindness. At the same time, this paper presents certain
      changes of the eye fundus and mode of their treatment. MATERIAL AND METHOD:
      Analysis of studies published on diabetic retinopathy and screening conducted in
      developed countries, with creating an algorithm for follow-up of diabetic retinal
      changes and their management. CONCLUSION: Timely detection and treatment of
      diabetic retinopathy with application of protocols in developed countries as well
      as parallel correction of systemic risk factors for progression of diabetic
      retinopathy will reduce the possibility of visual impairment in diabetics due to
      retinal complications. At the same time expenditures related to more complicated
      and less effective surgical procedures will be reduced along with the societal
      concern.

PMID- 25754508
TI  - Analysis of radiographic bone parameters throughout the surgical lengthening and
      deformity correction of extremities.
AB  - BACKGROUND: Radiographic examination of extremities in surgical lengthening
      and/or correction of deformities is of crucial importance for the assessment of
      new bone formation. The purpose of this study is to confirm the diagnostic value
      of radiography in precise detection of bone parameters in various lengthening or
      correction stages in patients treated by limb-lengthening and deformity
      correction. PATIENTS AND METHODS: 50 patients were treated by the Ilizarov method
      of limb lengthening or deformity correction at the University Orthopaedic Surgery
      Clinic in Skopje, and analysed over the period from 2006 to 2012. The patients
      were divided into two groups. The first group consisted of 27 patients with limb
      lengthening because of congenital shortening. The second group consisted of 23
      patients treated for acquired limb deformities. The results in both groups were
      received in three stages of new bone formation and were based on the appearance
      of 3 radiographic parameters at the distraction/compression site. RESULTS: The
      differences between the presence of all radiographic bone parameters in different
      stages of new bone formation were statistically signficant in both groups,
      especially the presence of the cortical margin in the first group (Cochran
      Q=34.43, df=2, p=0.00000). The comparative analysis between the two groups showed
      a statistically significant difference in the presence of initial bone elements
      and cystic formations only in the first stage. DISCUSSION AND CONCLUSIONS: Almost
      no statistical significance in the differences between both groups of patients
      with regard to 3 radiographic parameters in 3 stages of new bone formation,
      indicates a minor influence of the etiopathogenetic background on the new bone
      formation in patients treated by gradual lengthening or correction of limb
      deformities.

PMID- 25754509
TI  - Role of humoral mechanisms in etiology of lichen planus.
AB  - AIM: To examine the role of IgA, CIC and component C3 as indicators of humoral
      immune response in the etiopathogenesis of oral erosive lichen planus (OELP).
      MATERIAL AND METHOD: The study comprised 19 patients with OELP whose samples of
      blood, saliva and tissue were obtained after carefully taken medical history and
      clinical examination. Samples of oral mucosa were taken from the site of lesion,
      i.e. exclusively from buccal mucosa (1 cm in width and length), and from the deep
      epithelium as well as a segment from the lamina propria. Determination of
      immunoglobulins in serum and saliva, and determination of component C3, was done
      using the micro-elisa technique by Rook&Cameron, Engvall and Ulman. Determination
      of CIC in serum and mixed saliva was done with the PEG (polyethylene glycol)
      method. Determination of immunoglobulin A and component C3 in biopsy material was
      done with direct immunofluorescence. RESULTS: Levels of immunoglobulin A in serum
      in OELP during exacerbation were decreased (1.04+/-0.49 gr/l) and during
      remission increased (5.92+/-0.62) in comparison with the control group (p<0.001).
      Levels of CIC during exacerbation and remission were increased (p<0.001), and
      component C3 levels were increased in both examined phases in the examined group
      compared with the control group (p<0.05). Deposits of IgA were registered in one
      (5.88%) patient with OELP and component C3 was registered in 3 (17.64%) patients.
      CONCLUSION: Changes in IgA values, as well as CIC and component C3, may correlate
      with changes in oral mucosa emphasizing the role of humoral immune response in
      the pathogenesis of oral lichen planus.

PMID- 25754510
TI  - Therapeutic effect of proaftol in treatment of recurrent aphthous stomatitis.
AB  - Recurrent aphthous stomatitis (RAS) is a quite frequent, painful, ulcerative
      disease that affects the lining of the oral cavity and has an unknown etiology.
      The aim of this article is to examine the impact of the medication proaftol on
      epithelization speed and severity of pain in patients with RAS. In this
      randomized, double-blind, placebo-controlled study respondents were divided into
      two groups where one group was treated with proaftol spray and the other with a
      placebo. Aphthae considered for treatment had a diameter of 5-6 mm. The
      participants were given instruction on the use of the spray, two sprayings on the
      place of the aphtae 3-4 times a day. We examined two parameters in the
      symptomatology of RAS-lesion size (mm) and pain intensity (noted on four
      subjective levels: 0-no pain, 1-discomfort, 2-moderate pain, 3-severe pain).
      These parameters were noted on the baseline, the third, the fifth and the eighth
      days of examination. RESULTS: A significant faster reduction of the dimension of
      aphthous ulcers in patients treated with proaftol 3rd day p<0.001, 5th day
      p<0.0006, 8th day full epithelization in the control group. The magnitude of pain
      in the experimental compared with the control group on 3rd, 5th and 8th day was
      also significantly reduced: p<0.0001, p<0.007, p<0.007 respectively. CONCLUSION:
      The use of proaftol positively influences the rate of epithelization and
      reduction of subjective feeling of pain in patients with RAS. The action of
      propolis should be the goal of studies with a larger number of subjects.

PMID- 25754511
TI  - History and development of anaesthesiology (with resuscitation and intensive
      medicine) in the Republic of Macedonia.
AB  - AIM: To present a chronological overview of the most important events and actors
      that have marked the history of anaesthesiology and intensive treatment in R.
      Macedonia since its beginnings in the 1950s. METHOD: Retrospective study based on
      archive materials, published literature and jubilee publications, as well as the
      memories of individuals who have worked in the field of anaesthesiology in the
      past period. RESULTS: Between the two World Wars the first anaesthesia procedures
      were handled by surgeons. After World War II, the development of anaesthesia in
      R. Macedonia could be divided into two periods: before 1965 and after 1965.
      Before 1965 anaesthesia was mainly given by technicians trained on courses, and
      after this year anaesthesiology was taken over by anaesthesiologists who had
      specialized at the Faculty of Medicine in Skopje. In 1985 the number of
      anaesthesiologists was 100, and today it exceeds 250. The most important figures
      in the history of Macedonian anaesthesiology are: Dr. Risto Ivanovski, who worked
      from 1954-78, and Prof. Dr. Vladimir Andonov, who worked as an anaesthesiologist
      from 1965-99. Both of them are doyens who contributed a lot to the development of
      the anaesthesiology service and education of anaesthesiologists in R. Macedonia.
      Intensive treatment had started in 1955, but in real terms it has been performed
      since 1966, when artificial ventilators were introduced. The modern Intensive
      Care Department was opened at the Surgical Clinic in 1995 and it was followed in
      other hospitals in the state. The Department of Anaesthesiology has existed since
      1975, and it has made a huge contribution to the education of professionals who
      apply modern principles in emergency medicine and intensive care. CONCLUSION:
      From modest beginnings in the 1950s, anaesthesiology today in R. Macedonia has
      developed well organized activity that successfully follow the trends of modern
      medicine in the field of anesthesiology, resuscitation, intensive care and pain
      treatment.

PMID- 25754512
TI  - Seventy years since the establishment of the Skopje Military Hospital, 1944-2014.
AB  - AIM: To present the phases and activities over the period of the existence and
      work of the Military Hospital in Skopje, from its establishment in 1944 to its
      transformation on 01.01.2010. METHODS: A retrospective study based on available
      archive materials, encyclopaedias and other sources of information and review of
      the relevant literature, and personal experiences, observations and memories of
      the authors and others. RESULTS: During the War of 1941-1945, the larger military
      units formed hospitals. On 15.11.1944, the hospital of the Headquarters of the
      People's Liberation Army and Partisan Detachments of Macedonia was moved from the
      village Gorno Vranovci to Skopje. The Military Hospital in Skopje received the
      status of permanent hospital of the 5th Army, and from 1945-1963 worked at the
      "Crescent" facility. After the earthquake in 1963, due to damage, it was partly
      moved to the hospital in Nish, and partly dispersed in pavilions. In 1971 a new
      military medical complex was put into operation, in which most belonged to the
      Military Hospital in Skopje. Until 1992 the military sanitation service was under
      the command of the then Yugoslav People's Army, and then was under the
      jurisdiction of the Ministry of Defence of R. Macedonia. From 10.04.1992 to
      2.06.1992 it served as a Military Hospital of the Army of R. Macedonia and then
      as the "Centre of Military Health Institutions" until 26.10.2001. Then it was
      renamed the Military Hospital of the Army of R. Macedonia until March 2008, when
      converted to the Ministry of Defence as "Military Health Service--Military
      Hospital". On 01.01.2010 the Military Hospital was reshaped into: PHI Eighth of
      September City General Hospital, Skopje, and the Military Medical Centre.
      CONCLUSION: The Military Hospital in Skopje over the period of its existence has
      been one of the key specialist-consultative and hospital facilities in the health
      system in R. Macedonia for providing health care to military beneficiaries and
      the civilian population.

PMID- 25754513
TI  - Difference in Striga-susceptibility is reflected in strigolactone secretion
      profile, but not in compatibility and host preference in arbuscular mycorrhizal
      symbiosis in two maize cultivars.
AB  - Strigolactones released from plant roots trigger both seed germination of
      parasitic weeds such as Striga spp. and hyphal branching of the symbionts
      arbuscular mycorrhizal (AM) fungi. Generally, strigolactone composition in
      exudates is quantitatively and qualitatively different among plants, which may be
      involved in susceptibility and host specificity in the parasite-plant
      interactions. We hypothesized that difference in strigolactone composition would
      have a significant impact on compatibility and host specificity/preference in AM
      symbiosis. Strigolactones in root exudates of Striga-susceptible (Pioneer 3253)
      and -resistant (KST 94) maize (Zea mays) cultivars were characterized by LC-MS/MS
      combined with germination assay using Striga hermonthica seeds. Levels of
      colonization and community compositions of AM fungi in the two cultivars were
      investigated in field and glasshouse experiments. 5-Deoxystrigol was exuded
      exclusively by the susceptible cultivar, while the resistant cultivar mainly
      exuded sorgomol. Despite the distinctive difference in strigolactone composition,
      the levels of AM colonization and the community compositions were not different
      between the cultivars. The present study demonstrated that the difference in
      strigolactone composition has no appreciable impact on AM symbiosis, at least in
      the two maize cultivars, and further suggests that the traits involved in Striga
      resistance are not necessarily accompanied by reduction in compatibility to AM
      fungi. 

PMID- 25754514
TI  - Heart rate variability stabilization in athletes: towards more convenient data
      acquisition.
AB  - Resting heart rate variability (HRV) is a potentially useful marker to consider
      for monitoring training status in athletes. However, traditional HRV data
      collection methodology requires a 5-min recording period preceded by a 5-min
      stabilization period. This lengthy process may limit HRV monitoring in the field
      due to time constraints and high compliance demands of athletes. Investigation
      into more practical methodology for HRV data acquisitions is required. The aim of
      this study was to determine the time course for stabilization of ECG-derived
      lnRMSSD from traditional HRV recordings. Ten-minute supine ECG measures were
      obtained in ten male and ten female collegiate cross-country athletes. The first
      5 min for each ECG was separately analysed in successive 1-min intervals as
      follows: minutes 0-1 (lnRMSSD0-1 ), 1-2 (lnRMSSD1-2 ), 2-3 (lnRMSSD2-3 ), 3-4
      (lnRMSSD3-4 ) and 4-5 (lnRMSSD4-5 ). Each 1-min lnRMSSD segment was then
      sequentially compared to lnRMSSD of the 5- to 10-min ECG segment, which was
      considered the criterion (lnRMSSDC riterion ). There were no significant
      differences between each 1-min lnRMSSD segment and lnRMSSDC riterion , and the
      effect sizes were considered trivial (ES ranged from 0.07 to 0.12). In addition,
      the ICC for each 1-min segment compared to the criterion was near perfect (ICC
      values ranged from 0.92 to 0.97). The limits of agreement between the
      prerecording values and lnRMSSDC riterion ranged from +/-0.28 to +/-0.45 ms.
      These results lend support to shorter, more convenient ECG recording procedures
      for lnRMSSD assessment in athletes by reducing the prerecording stabilization
      period to 1 min. 

PMID- 25754515
TI  - Factors that discriminate age at menopause: A study of Bengali Hindu women of
      West Bengal.
AB  - OBJECTIVE: This study aims to investigate the factors that discriminate different
      menopausal age groups. METHODS: We selected 715 postmenopausal Bengali-speaking
      Hindu women from the State of West Bengal, India, who were married and had at
      least one child. We divided the participants into three groups based on the age
      at which they attained menopause: Group 1 (30-39 years), Group 2 (40-49 years),
      and Group 3 (50-55 years). A well-tested questionnaire was used to collect
      information on reproductive variables. RESULTS: We applied discriminant function
      analysis to identify the factors associated with different ages at menopause.
      Results show that factors like age at menarche, duration of breastfeeding of the
      last child, and age at first pregnancy discriminate the different menopausal age
      groups. CONCLUSION: We concluded that reproductive factors discriminate the three
      different menopausal age groups for this study population.

PMID- 25754516
TI  - Do attitudes toward societal structure predict beliefs about free will and
      achievement? Evidence from the Indian caste system.
AB  - Intuitive theories about the malleability of intellectual ability affect our
      motivation and achievement in life. But how are such theories shaped by the
      culture in which an individual is raised? We addressed this question by exploring
      how Indian children's and adults' attitudes toward the Hindu caste system--and
      its deterministic worldview--are related to differences in their intuitive
      theories. Strikingly, we found that, beginning at least in middle school and
      continuing into adulthood, individuals who placed more importance on caste were
      more likely to adopt deterministic intuitive theories. We also found a
      developmental change in the scope of this relationship, such that in children,
      caste attitudes were linked only to abstract beliefs about personal freedom, but
      that by adulthood, caste attitudes were also linked to beliefs about the
      potential achievement of members of different castes, personal intellectual
      ability, and personality attributes. These results are the first to directly
      relate the societal structure in which a person is raised to the specific
      intuitive theories they adopt.

PMID- 25754517
TI  - Action-Based Learning of Multistate Objects in the Medial Temporal Lobe.
AB  - Actions constrain perception by changing the appearance of objects in the
      environment. As such, they provide an interactive basis for learning the
      structure of visual input. If an action systematically transforms one stimulus
      into another, then these stimuli are more likely to reflect different states of
      the same persisting object over time. Here we show that such multistate objects
      are represented in the human medial temporal lobe--the result of a mechanism in
      which actions influence associative learning of how objects transition between
      states. We further demonstrate that greater recruitment of these action-based
      representations during object perception is accompanied by attenuated activity in
      stimulus-selective visual cortex. In this way, our interactions with the
      environment help build visual knowledge that predictively facilitates perceptual
      processing.

PMID- 25754519
TI  - Clinical associations of anosognosia in mild cognitive impairment and Alzheimer's
      disease.
AB  - AIMS AND OBJECTIVE: While loss of insight of cognitive deficits is a common
      phenomenon in patients with Alzheimer's disease (AD), there is a lack of
      consensus regarding the presence of impaired insight among patients with mild
      cognitive impairment (MCI). We aim to investigate the clinical, cognitive, and
      behavioral associations of anosognosia in AD and MCI subjects. METHODS: A
      consecutive series of 87 subjects (30 healthy older patients, 21 MCI, and 36 AD)
      each accompanied by a caregiver, underwent clinical assessment including the
      evaluation of insight using the Anosognosia Questionnaire for Dementia (AQD). We
      also separately assessed Intellectual Function (AQD-IF) and Behavior domains of
      the AQD scale. Regression models were subsequently used to investigate
      associations of AQD scores with cognitive and other neuropsychiatric symptoms,
      including depression and apathy. RESULTS: Both AD and MCI groups demonstrated
      significant anosognosia compared with the healthy control group. In the AD group,
      55.6% had "Mild Anosognosia," and 27.8% had "Severe Anosognosia." In the MCI
      group, 42.9% showed "Mild Anosognosia," and 9.5% had "Severe Anosognosia."
      Greater levels of AQD-Total and AQD-IF were associated with lower Mini-mental
      state examination and higher apathy scores in the AD group. In the MCI group,
      caregiver burden was significantly associated with AQD-Total (p = 0.016) and AQD
      IF (p = 0.039). CONCLUSION: The results indicated that anosognosia is common in
      both AD and MCI patients and associated with cognitive dysfunction and apathy in
      AD. The findings of this study warrant further research to delineate the
      mechanisms of anosognosia as it poses a challenge to treatment outcomes.

PMID- 25754518
TI  - The Frontal Control of Stopping.
AB  - Stopping is a critical aspect of brain function. Like other voluntary actions, it
      is defined by its context as much as by its execution. Its neural substrate must
      therefore reflect both. Here, we distinguish those elements of the underlying
      brain circuit that preferentially reflect contextual aspects of stopping from
      those related to its execution. Contextual complexity of stopping was modulated
      using a novel "Stop/Change-signal" task, which also allowed us to parameterize
      the duration of the stopping process. Human magnetoencephalographic activity and
      behavioral responses were simultaneously recorded. Whereas theta/alpha frequency
      activity in the right inferior frontal gyrus was most closely associated with the
      duration of the stopping process, earlier gamma frequency activity in the pre
      supplementary motor area was unique in showing contextual modulation. These
      results differentiate the roles of 2 key frontal regions involved in stopping, a
      crucial aspect of behavioral control. 

PMID- 25754520
TI  - Health status, behavior, and care of lesbian and bisexual women in Israel.
AB  - INTRODUCTION: Lesbian and bisexual women (LBs) have unique health needs compared
      with heterosexual women (HW). AIM: This study aimed to associate the health
      status of LB, their health behavior, disclosure of sexual orientation (SO), and
      avoidance of health care with that of HW. METHODS: Participants in this cross
      sectional study completed anonymous questionnaires, which were distributed in
      Internet sites and public venues in Israel, comparing health behaviors and
      outcomes between LB and HW. MAIN OUTCOME MEASURES: Health outcomes included
      subjective health status, general practitioner or gynecologist visit in the last
      6 months, and satisfaction from the Israeli healthcare system. RESULTS: In 2012,
      681 (34.4%) lesbians, 242 (13.5%) bisexual women, and 937 (52.1%) HW completed
      the questionnaire. In comparison with HW, LBs were more commonly single, used
      drugs/alcohol, smoked, experienced eating disorders, and reported an earlier
      sexual debut. In comparison with all women, lesbians performed less physical
      activities and were more satisfied with their body weight, whereas bisexuals had
      riskier sexual behavior and reported more verbal/physical abuse. LB reported more
      emergency room visits, more visits to psychiatrists, yet underwent Pap smears
      less frequently compared with HW. In a multivariate analysis, lesbians had fewer
      gynecologists' visits and were less satisfied with the healthcare system than HW,
      whereas bisexuals visited their general practitioner or gynecologist less
      frequently and were less satisfied with the primary healthcare system. Lesbians
      were more likely to disclose their SO with their doctors than bisexuals and were
      satisfied with the disclosure. Nondisclosure of SO was correlated with poor
      subjective health status. The interaction between being bisexual and
      nondisclosure of SO was strong. CONCLUSIONS: LB utilized health care less
      frequently than HW, resulting in unmet medical needs. SO disclosure was
      associated with better healthcare utilization and health outcomes, especially
      among bisexuals. Providers should be trained about LB's unique health needs and
      improve their communication skills to encourage SO disclosure.

PMID- 25754522
TI  - Cadherin is involved in the action of Bacillus thuringiensis toxins Cry1Ac and
      Cry2Aa in the beet armyworm, Spodoptera exigua.
AB  - Bacillus thuringiensis (Bt) insecticidal crystal (Cry) proteins are effective
      against some insect pests in sprays and transgenic crops, although the evolution
      of resistance could threaten the long-term efficacy of such Bt use. One strategy
      to delay resistance to Bt crops is to "pyramid" two or more Bt proteins that bind
      to distinct receptor proteins within the insect midgut. The most common Bt
      pyramid in cotton (Gossypium hirsutum L.) employs Cry1Ac with Cry2Ab to target
      several key lepidopteran pests, including the beet armyworm, Spodoptera exigua
      (Hubner), which is a serious migratory pest of many vegetable crops and is
      increasingly important in cotton in China. While cadherin and aminopeptidase-N
      are key receptors of Cry1 toxins in many lepidopterans including S. exigua, the
      receptor for Cry2A toxins remains poorly characterized. Here, we show that a
      heterologous expressed peptide corresponding to cadherin repeat 7 to the membrane
      proximal extracellular domain (CR7-MPED) in the S. exigua cadherin 1b (SeCad1b)
      binds Cry1Ac and Cry2Aa. Moreover, SeCad1b transcription was suppressed in S.
      exigua larvae by oral RNA interference and susceptibility to Cry1Ac and Cry2Aa
      was significantly reduced. These results indicate that SeCad1b plays important
      functional roles of both Cry1Ac and Cry2Aa, having major implications for
      resistance management for S. exigua in Bt crops. 

PMID- 25754521
TI  - Deletion of the Sm1 encoding motif in the lsm gene results in distinct changes in
      the transcriptome and enhanced swarming activity of Haloferax cells.
AB  - Members of the Sm protein family are important for the cellular RNA metabolism in
      all three domains of life. The family includes archaeal and eukaryotic Lsm
      proteins, eukaryotic Sm proteins and archaeal and bacterial Hfq proteins. While
      several studies concerning the bacterial and eukaryotic family members have been
      published, little is known about the archaeal Lsm proteins. Although structures
      for several archaeal Lsm proteins have been solved already more than ten years
      ago, we still do not know much about their biological function, however one can
      confidently propose that the archaeal Lsm proteins will also be involved in RNA
      metabolism. Therefore, we investigated this protein in the halophilic archaeon
      Haloferax volcanii. The Haloferax genome encodes a single Lsm protein, the lsm
      gene overlaps and is co-transcribed with the gene for the ribosomal L37.eR
      protein. Here, we show that the reading frame of the lsm gene contains a promoter
      which regulates expression of the overlapping rpl37R gene. This rpl37R specific
      promoter ensures high expression of the rpl37R gene in exponential growth phase.
      To investigate the biological function of the Lsm protein we generated a lsm
      deletion mutant that had the coding sequence for the Sm1 motif removed but still
      contained the internal promoter for the downstream rpl37R gene. The transcriptome
      of this deletion mutant was compared to the wild type transcriptome, revealing
      that several genes are down-regulated and many genes are up-regulated in the
      deletion strain. Northern blot analyses confirmed down-regulation of two genes.
      In addition, the deletion strain showed a gain of function in swarming, in
      congruence with the up-regulation of transcripts encoding proteins required for
      motility. 

PMID- 25754523
TI  - Lack of stress responses to long-term effects of corticosterone in Caps2 knockout
      mice.
AB  - Chronic stress is associated with anxiety and depressive disorders, and can cause
      weight gain. Ca(2+)-dependent activator protein for secretion 2 (CAPS2) is
      involved in insulin release. Caps2 knockout (KO) mice exhibit decreased body
      weight, reduced glucose-induced insulin release, and abnormal psychiatric
      behaviors. We chronically administered the stress hormone corticosterone (CORT),
      which induces anxiety/depressive-like behavior and normally increases plasma
      insulin levels, via the drinking water for 10 weeks, and we examined the stress
      response in KO mice. Chronic CORT exposure inhibited stress-induced serum CORT
      elevation in wild-type (WT) mice, but not in KO mice. Poor weight gain in CORT
      treated animals was observed until week 6 in WT mice, but persisted for the
      entire duration of the experiment in KO mice, although there is no difference in
      drug*genotype interaction. Among KO mice, food consumption was unchanged, while
      water consumption was higher, over the duration of the experiment in CORT-treated
      animals, compared with untreated animals. Moreover, serum insulin and leptin
      levels were increased in CORT-treated WT mice, but not in KO mice. Lastly, both
      WT and KO mice displayed anxiety/depressive-like behavior after CORT
      administration. These results suggest that Caps2 KO mice have altered endocrine
      responses to CORT administration, while maintaining CORT-induced
      anxiety/depressive-like behavior. 

PMID- 25754524
TI  - Electronic spectra and DFT calculations of some pyrimido[1,2-a]benzimidazole
      derivatives.
AB  - Ground state properties of 2,4-diphenyl-1,4-dihydrobenzo[4,5]imidazo[1,2
      a]pyrimidine, compound 1, and its derivatives are investigated experimentally and
      theoretically in Dioxane and DMF. The calculations show that all the studied
      compounds (1-7) are non-planar, resulting in a significant impact on the
      electronic and structural properties. The ground state properties of compounds 1
      7 at B3LYP/6-311G (d, p) show that compound 5 has the lowest EHOMO, ELUMO, and
      DeltaE indicating highest reactivity. Compound 7 is found to have the highest
      polarity. The observed UV spectra in Dioxane and DMF of compounds 1-4 show 2
      bands, while compounds 5-7 show 4 bands in both solvents. Band maxima (lambdamax)
      and intensities of the spectra are found to have solvent dependence reflected as
      blue and red shifts. The theoretical spectra computed at TD-B3LYP/6-311G (d, p)
      in gas phase, Dioxane and DMF indicate a good agreement with the observed
      spectra.

PMID- 25754526
TI  - Dynamic contrast-enhanced ultrasound parametric imaging for the detection of
      prostate cancer.
AB  - OBJECTIVE: To investigate the value of dynamic contrast-enhanced (DCE)
      ultrasonography (US) and software-generated parametric maps in predicting biopsy
      outcome and their potential to reduce the amount of negative biopsy cores.
      MATERIALS AND METHODS: For 651 prostate biopsy locations (82 consecutive
      patients) we correlated the interpretation of DCE-US recordings with and without
      parametric maps with biopsy results. The parametric maps were generated by
      software which extracts perfusion parameters that differentiate benign from
      malignant tissue from DCE-US recordings. We performed a stringent analysis (all
      tumours) and a clinical analysis (clinically significant tumours). We calculated
      the potential reduction in biopsies (benign on imaging) and the resultant missed
      positive biopsies (false-negatives). Additionally, we evaluated the performance
      in terms of sensitivity, specificity negative predictive value (NPV) and positive
      predictive value (PPV) on a per-prostate level. RESULTS: Based on DCE-US, 470/651
      (72.2%) of biopsy locations appeared benign, resulting in 40 false-negatives
      (8.5%), considering clinically significant tumours only. Including parametric
      maps, 411/651 (63.1%) of the biopsy locations appeared benign, resulting in 23
      false-negatives (5.6%). In the per-prostate clinical analysis, DCE-US classified
      38/82 prostates as benign, missing eight diagnoses. Including parametric maps,
      31/82 prostates appeared benign, missing three diagnoses. Sensitivity,
      specificity, PPV and NPV were 73, 58, 50 and 79%, respectively, for DCE-US alone
      and 91, 56, 57 and 90%, respectively, with parametric maps. CONCLUSION: The
      interpretation of DCE-US with parametric maps allows good prediction of biopsy
      outcome. A two-thirds reduction in biopsy cores seems feasible with only a modest
      decrease in cancer diagnosis.

PMID- 25754525
TI  - Preventive pancreatic stents in the management of acute biliary pancreatitis
      (PREPAST trial): pre-study protocol for a multicenter, prospective, randomized,
      interventional, controlled trial.
AB  - BACKGROUND: The outcome of the most common biliary form of acute pancreatitis has
      not changed even with the better described indications for early endoscopic
      intervention. It may be due to the fact that this intrevention theoretically can
      cause further pancreatic injury or cannot always relieve the pancreatic duct
      obstruction. We hypothesize that maintaining the outflow of the pancreatic duct
      with preventive pancreatic stents at the early ERCP improves the outcome of acute
      biliary pancreatitis. METHODS/DESIGN: PREPAST is a prospective, randomized,
      controlled, multicenter trial. Patients with acute biliary pancreatitis with
      coexisting cholangitis are randomized to undergo urgent endoscopic intervention
      with or without pancreatic stenting within 48 h from the onset of pain, and in
      addition patients without signs of cholangitis but cholestasis are randomly
      allocated to recieve conservative treatment or early endoscopic intervention with
      or without pancreatic stenting within 48 h from the onset of pain. Patients
      without acute cholangitis and signs of cholestasis recieve conservative
      treatment. 230 patients are planned to be enrolled during a 48 months period from
      different centers. The primary endpoint is the outcome of acute biliary
      pancreatitis as described by the latest guidelines. Secondary endpoints include
      mortality data, and other variables not analyzed as a primary endpoint but
      related to the pancreatitis or the pancreatic stenting. DISCUSSION: The PREPAST
      trial is designed to show whether early endoscopic intervention with the usage of
      preventive pancreatic stenting improves the outcome of acute biliary
      pancreatitis. The study has been registered at the International Standard
      Randomised Controlled Trial Number (ISRCTN) Register (trial ID: ISRCTN13517695).

PMID- 25754527
TI  - Comparison of the international normalized ratio levels obtained by portable
      coagulometer and laboratory in a clinic specializing in oral anticoagulation.
AB  - INTRODUCTION: Therapy with Vitamin K antagonists (VKA) is effective in reducing
      thromboembolic events in various diseases. There are limitations however, which
      limit clinical handling and maintaining INR within therapeutic range. Studies
      have shown that portable coagulometers, when compared to laboratory tests, are
      more practical and provide better patient adherence and involvement toward
      treatment which results in better INR control. This study aimed to evaluate
      laboratory obtained INR results compared to two different portable coagulometers.
      METHODS: A prospective study which monitored 1009 patients using VKA in the
      Anticoagulation Clinic at the Institute Dante Pazzanese of Cardiology in Sao
      Paulo between July and September 2012. Patient INR values were obtained by the
      laboratory through venipuncture and then compared to INR values obtained by
      capillary puncture from two different portable coagulometers. RESULTS: Overall,
      1009 patients were included in the study; among these, 520 (51.5%) are male with
      average age of 59.6 years (13-91). The more common indications were atrial
      fibrillation (49.9%) and mechanical prosthesis (33.7%). The correlation
      coefficient was of 0.95 with and 0.88 with INRatio PT Monitor((r)) compared to
      laboratory. In patients with INR < 2 (lower than therapeutic range), the
      coefficient was 0.92 and 0.81 for CoaguChek XS plus((r)) and INRatio PT
      Monitor((r)) respectively. In patients within therapeutic range (INR 2-3), the
      coefficient was 0.86 with CoaguChek XS Plus((r)) and 0.76 with INRatio PT
      Monitor((r)) . For INR above therapeutic range (INR > 3.0) the correlation was
      0.80 with CoaguChek XS Plus((r)) and 0.54 with INRatio PT Monitor((r)) . As for
      concordance between methods, the intraclass correlation coefficients (ICC) were
      slightly smaller than those previously stated (ICC = 0.899 with CoaguChek XS
      Plus((r)) and ICC = 0.716 with INRatio PT Monitor((r)) ). CONCLUSION: The use of
      portable coagulometers was comparable to laboratory tests and better correlation
      coefficients were observed with CoaguChek XS Plus((r)) and in patients with INR
      lower or within therapeutic range. Portable coagulometers proved to be a useful
      and reliable tool for INR control in patients using VKA.

PMID- 25754528
TI  - Pupil size tracks perceptual content and surprise.
AB  - Changes in pupil size at constant light levels reflect the activity of
      neuromodulatory brainstem centers that control global brain state. These
      endogenously driven pupil dynamics can be synchronized with cognitive acts. For
      example, the pupil dilates during the spontaneous switches of perception of a
      constant sensory input in bistable perceptual illusions. It is unknown whether
      this pupil dilation only indicates the occurrence of perceptual switches, or also
      their content. Here, we measured pupil diameter in human subjects reporting the
      subjective disappearance and re-appearance of a physically constant visual target
      surrounded by a moving pattern ('motion-induced blindness' illusion). We show
      that the pupil dilates during the perceptual switches in the illusion and a
      stimulus-evoked 'replay' of that illusion. Critically, the switch-related pupil
      dilation encodes perceptual content, with larger amplitude for disappearance than
      re-appearance. This difference in pupil response amplitude enables prediction of
      the type of report (disappearance vs. re-appearance) on individual switches
      (receiver-operating characteristic: 61%). The amplitude difference is independent
      of the relative durations of target-visible and target-invisible intervals and
      subjects' overt behavioral report of the perceptual switches. Further, we show
      that pupil dilation during the replay also scales with the level of surprise
      about the timing of switches, but there is no evidence for an interaction between
      the effects of surprise and perceptual content on the pupil response. Taken
      together, our results suggest that pupil-linked brain systems track both the
      content of, and surprise about, perceptual events. 

PMID- 25754529
TI  - Prognostic impact of hyponatraemia in patients with colorectal cancer.

PMID- 25754530
TI  - Do small dual-task costs reflect ideomotor compatibility or the absence of
      crosstalk?
AB  - Dual-task costs can be greatly reduced or even eliminated when both tasks use
      highly-compatible S-R associations. According to Greenwald (Journal of
      Experimental Psychology: Human Perception and Performance, 30, 632-636, 2003),
      this occurs because the appropriate response can be accessed without engaging
      performance-limiting response selection processes, a proposal consistent with the
      embodied cognition framework in that it suggests that stimuli can automatically
      activate motor codes (e.g., Pezzulo et al., New Ideas in Psychology, 31(3), 270
      290, 2013). To test this account, we reversed the stimulus-response mappings for
      one or both tasks so that some participants had to "do the opposite" of what they
      perceived. In these reversed conditions, stimuli resembled the environmental
      outcome of the alternative (incorrect) response. Nonetheless, reversed tasks were
      performed without costs even when paired with an unreversed task. This finding
      suggests that the separation of the central codes across tasks (e.g., Wickens,
      1984) is more critical than the specific S-R relationships; dual-task costs can
      be avoided when the tasks engage distinct modality-based systems.

PMID- 25754531
TI  - The Characteristics of Local Support Systems, and the Roles of Professionals, in
      Supporting Families where a Mother has an Intellectual Disability.
AB  - BACKGROUND: There might be a need for support for families where the mother has
      an intellectual disability, in order to counteract the effects of potential
      parental inadequacy and other detrimental aspects of the family situation. The
      purpose of this study was to describe how professionals characterized such
      support and the collaboration required. MATERIALS AND METHODS: Focus group
      interviews involving 29 professionals were conducted and analysed using content
      analysis. RESULTS: Five themes were identified: The roles and activities of the
      professionals involved; ways in which needs of support are identified; problems
      in identifying mothers with an intellectual disability; how professionals
      coordinate their support and work together; and the dilemma concerning
      legislative actions. CONCLUSIONS: By identifying both fruitful and problematic
      aspects of professional support, the findings may be used to enhance future
      support. More efficient chains of information and improved inter-sector
      collaboration between professions may further enhance the support practices.

PMID- 25754532
TI  - Symptom data reanalysis disconfirms Parker et al.'s claim that latent class
      analysis identifies melancholic depression.

PMID- 25754533
TI  - Evaluation of orbital arteries with colour Doppler ultrasonography in patients
      with psoriasis.
AB  - AIM: To evaluate the blood flow in arteries of the orbit in patients with
      psoriasis. METHODS: In total, 30 patients with psoriasis and 30 healthy control
      subjects were recruited to the study. Standard ophthalmic evaluation, fundus
      examination and retrobulbar colour Doppler ultrasonography assessment were
      performed. The ophthalmic, posterior ciliary and central arteries were evaluated,
      and peak systolic blood flow velocity, end diastolic velocity, resistance index
      and pulsatility index were measured. Results of the measurements were compared
      between the two study groups. RESULTS: There were significant differences in
      blood flow parameters of the orbital arteries between the psoriasis group and the
      control group. CONCLUSIONS: The haemodynamics of the orbit might be affected in
      patients with psoriasis.

PMID- 25754534
TI  - Isolation and characterization of Bacillus subtilis CH16 strain from chicken
      gastrointestinal tracts for use as a feed supplement to promote weight gain in
      broilers.
AB  - Spore-forming bacterial strains were isolated from chicken gastrointestinal
      tracts to develop a heat-stable feed supplement that promotes weight gain in
      broilers. Seven Bacillus strains having more than 90% sporulation were screened
      from the isolates and identified to be closely related with Bacillus subtilis and
      Bacillus licheniformis. Of the seven strains, B. subtilis CH16 was selected to
      develop a feed supplement for broilers, because it formed 100% heat-stable
      spores, grew rapidly at 42 degrees C and quickly formed a biofilm. In large-scale
      trials in broilers (n >= 1150 per group), the group fed CH16 (3 * 10(6) CFU g(-1)
      pellet) showed higher average daily gain (ADG = 61.16) and lower food conversion
      ratio (FCR = 1.696) than did the group fed B. licheniformis CH22 (ADG = 57.10 and
      FCR = 1.792), the group fed B. subtilis HU58 (ADG = 51.90 and FCR = 1.868),
      BioPlus group (ADG = 59.32 and FCR = 1.807) and the control group (ADG = 56.02
      and FCR = 1.880). In conclusion, CH16 spores significantly increased ADG by 9.17%
      and reduced FCR by 9.79% in broilers. The result supports the use of B. subtilis
      CH16 of chicken intestinal origin as a feed supplement that promote weight gain
      in broilers. Significance and impact of the study: This study reports screening
      of Bacillus strains isolated from chicken gastrointestinal tracts for development
      of a feed supplement that promote weight gain in broilers. Of the seven Bacillus
      isolates with high sporulation efficiency (>=90%), Bacillus subtilis CH16 strain
      showed the best growth and biofilm formation at body temperature of broilers (42
      degrees C). In large-scale trials in broilers (n >= 1150 per group), CH16 spores
      induced a 9.17% increase in daily weight gain (ADG) and a 9.79% reduction in FCR
      while the commercial BioPlus((r)) YC induced only a 5.89% increase in ADG and a
      3.88% reduction in FCR.

PMID- 25754535
TI  - Niemann-Pick type C2 protein regulates liver cancer progression via modulating
      ERK1/2 pathway: Clinicopathological correlations and therapeutical implications.
AB  - Primary hepatocellular carcinoma (HCC) is the fifth most common malignancy
      worldwide and the third leading cause of cancer-related death. It is important to
      identify new targets for early diagnosis and treatment of HCC. Niemann-Pick type
      C2 (NPC2) plays an important role in the regulation of intracellular cholesterol
      homeostasis via direct binding with free cholesterol. However, little is known
      about the significance of NPC2 in HCC tumorigenesis. In this study, we showed
      that NPC2 is abundantly expressed in normal liver, but is downregulated in human
      HCC tissues. The patients with NPC2 downregulation expressed much higher alpha
      fetoprotein, multiple tumor type, vascular invasion, later pathological stage and
      shorter survival rate. Knockdown NPC2 in liver cancer cell lines promote cell
      proliferation, migration and xenograft tumorigenesis. In contrast, NPC2
      overexpression inhibits HuH7 promoted tumor growth. Furthermore, administration
      of hepatotropic adeno-associated virus 8 (AAV8) delivered NPC2 decreased the
      inflammatory infiltration, the expression of two early HCC markers-glypican 3 and
      survivin and suppressed the spontaneous HCC development in mice. To identify the
      NPC2-dependent mechanism, we emphasized on the status of MAPK/ERK signaling.
      MEK1/2 inhibitor treatment demonstrated that the expression of NPC2 affected the
      activation of ERK1/2 but not MEK1/2. In addition, cholesterol trafficking
      inhibitor treatment did not alter the cell proliferation and the activation of
      MEK/ERK. In conclusion, our study demonstrates that NPC2 may play an important
      role in negatively regulate cell proliferation and ERK1/2 activation that were
      independent of cholesterol accumulation. AAV-NPC2 may thus represent a new
      treatment strategy for liver cancer. 

PMID- 25754536
TI  - Detection of Merkel cell polyomavirus large T-antigen sequences in human central
      nervous system tumors.
AB  - Despite decades of epidemiological investigation, little is known about the
      etiology of the central nervous system (CNS) tumors, and few well-established
      risk factors have been recognized. This study tested the presence of Merkel cell
      polyomavirus (MCPyV), the only member of the Polyomaviridae family convincingly
      linked to human cancer, in diverse CNS malignancies. In total, 58 CNS tumor
      biopsies were analyzed for the MCPyV large T-antigen (LT-Ag) gene by quantitative
      real-time PCR. Merkel cell polyomavirus LT-Ag DNA load was determined as viral
      copies per cell and viral copies per microliter of purified genomic DNA from CNS
      tumor samples. The MCPyV LT-Ag sequence was detected in 34 (58.6%) of the 58
      tested samples. Viral LT-Ag was quantified in 19.0% of schwannomas, 13.8% of
      meningiomas, and 5.2% of pituitary adenomas. The difference between MCPyV
      positivity in different types of CNS malignancies was not statistically
      significant (P = 0.066). The mean LT-Ag copy number in 34 positive samples was
      744.5 +/- 737.7 and 0.056 * 10(-3)  +/- 0.091 * 10(-3) per microliter and per
      cell, respectively. Among MCPyV-positive CNS tumors, the mean MCPyV copy number
      was higher in meningiomas (993.8 +/- 853.2 copy per microliter and 0.098 * 10(-3)
      +/- 0.108 * 10(-3) copy per cell). Multiple linear regression analysis revealed
      statistically significant difference in MCPyV copy number between meningioma and
      other CNS tumor types, when the model was adjusted for age and sex (P = 0.024).
      This study shows the first evidence of the detection of MCPyV LT-Ag sequence at a
      low copy number in human CNS tumors.

PMID- 25754538
TI  - Automatic extraction of three-dimensional thoracic aorta geometric model from
      phase contrast MRI for morphometric and hemodynamic characterization.
AB  - PURPOSE: To propose and assess a new method that automatically extracts a three
      dimensional (3D) geometric model of the thoracic aorta (TA) from 3D cine phase
      contrast MRI (PCMRI) acquisitions. METHODS: The proposed method is composed of
      two steps: segmentation of the TA and creation of the 3D geometric model. The
      segmentation algorithm, based on Level Set, was set and applied to healthy
      subjects acquired in three different modalities (with and without SENSE reduction
      factors). Accuracy was evaluated using standard quality indices. The 3D model is
      characterized by the vessel surface mesh and its centerline; the comparison of
      models obtained from the three different datasets was also carried out in terms
      of radius of curvature (RC) and average tortuosity (AT). RESULTS: In all
      datasets, the segmentation quality indices confirmed very good agreement between
      manual and automatic contours (average symmetric distance < 1.44 mm, DICE
      Similarity Coefficient > 0.88). The 3D models extracted from the three datasets
      were found to be comparable, with differences of less than 10% for RC and 11% for
      AT. CONCLUSION: Our method was found effective on PCMRI data to provide a 3D
      geometric model of the TA, to support morphometric and hemodynamic
      characterization of the aorta.

PMID- 25754537
TI  - Haemanthus coccineus extract and its main bioactive component narciclasine
      display profound anti-inflammatory activities in vitro and in vivo.
AB  - Haemanthus coccineus extracts (HCE) have traditionally been used to treat a
      variety of diseases, like febrile colds or asthma. Since new therapeutic options
      against inflammatory processes are still urgently needed, we aimed to
      pharmacologically characterise the anti-inflammatory potential of HCEin vitro and
      in vivo and to identify the underlying bioactive component(s). The action of HCE
      on oedema formation and leucocyte infiltration were analysed in two murine models
      of inflammation (dermal oedema induced by arachidonic acid and croton oil; kidney
      injury caused by unilateral ureteral obstruction). The interaction of leucocytes
      with endothelial cells (ECs) as well as the activation parameters of these two
      cell types were analysed. Moreover, the nuclear factor kappaB (NFkappaB) pathway
      was investigated in detail in ECs. Using different fractions of HCE, the
      bioactive principle was identified. In vivo, HCE (450 mg/kg orally or 2 mg/kg
      intraperitoneally) inhibited oedema formation, leucocyte infiltration and
      cytokine synthesis. In vitro, HCE (100-300 ng/ml) blocked leucocyte-EC
      interaction as well as the activation of isolated leucocytes (cytokine synthesis
      and proliferation) and of primary ECs (adhesion molecule expression). HCE
      suppressed NFkappaB-dependent gene transcription in the endothelium, but did not
      interfere with the NFkappaB activation cascade (IkappaB degradation, p65 nuclear
      translocation and NFkappaB DNA-binding activity). The alkaloid narciclasine was
      elucidated as the bioactive compound responsible for the anti-inflammatory action
      of HCE. Our study highlights HCE and its main alkaloid narciclasine as novel
      interesting approach for the treatment of inflammation-related disorders. 

PMID- 25754540
TI  - Today and tomorrow: Reflections on health and medical geography.

PMID- 25754539
TI  - Genetic ancestry of the extinct Javan and Bali tigers.
AB  - The Bali (Panthera tigris balica) and Javan (P. t. sondaica) tigers are
      recognized as distinct tiger subspecies that went extinct in the 1940s and 1980s,
      respectively. Yet their genetic ancestry and taxonomic status remain
      controversial. Following ancient DNA procedures, we generated concatenated 1750bp
      mtDNA sequences from 23 museum samples including 11 voucher specimens from Java
      and Bali and compared these to diagnostic mtDNA sequences from 122 specimens of
      living tiger subspecies and the extinct Caspian tiger. The results revealed a
      close genetic affinity of the 3 groups from the Sunda Islands (Bali, Javan, and
      Sumatran tigers P. t. sumatrae). Bali and Javan mtDNA haplotypes differ from
      Sumatran haplotypes by 1-2 nucleotides, and the 3 island populations define a
      monophyletic assemblage distinctive and equidistant from other mainland
      subspecies. Despite this close phylogenetic relationship, no mtDNA haplotype was
      shared between Sumatran and Javan/Bali tigers, indicating little or no
      matrilineal gene flow among the islands after they were colonized. The close
      phylogenetic relationship among Sunda tiger subspecies suggests either recent
      colonization across the islands, or else a once continuous tiger population that
      had subsequently isolated into different island subspecies. This supports the
      hypothesis that the Sumatran tiger is the closest living relative to the extinct
      Javan and Bali tigers. 

PMID- 25754542
TI  - What can be learned from reporting no-treatment effect of distribution of upper
      limb training?

PMID- 25754541
TI  - Haemostatic function and biomarkers of endothelial damage before and after RBC
      transfusion in patients with haematologic disease.
AB  - BACKGROUND AND OBJECTIVES: Transfusion of red blood cells (RBC) is beneficial for
      the patient but can also be harmful, as randomized trials have demonstrated
      increased infection rates, bleeding and mortality. The study aim was to
      investigate the response of the vascular system (the haemostatic function and the
      endothelium) to RBC transfusion. MATERIALS AND METHODS: Blood was sampled from
      patients with various transfusion-dependent haematologic diseases before 1 and 24
      h after RBC transfusion. Primary and secondary haemostasis was evaluated by whole
      blood impedance aggregometry (Multiplate) and by thromboelastography (TEG).
      Samples were analysed by ELISA for biomarkers reflecting endothelial activation
      and damage (sICAM-1, syndecan-1, sThrombomodulin (sTM), sVE-Cadherin), platelet
      activation (sCD40L) and inflammation (hsCRP). RESULTS: A total of 58 patients
      were enrolled in the study. Median age was 71 years. Compared to before
      transfusion, patients had slightly reduced coagulability 1 h after RBC
      transfusion, assessed by TEG. However, transfusion of older RBC products (>14
      days) was associated with increased coagulability (all P < 0.05). The level of
      syndecan-1 increased slightly 24 h after transfusion (median 12.4 (IQR 9-23) vs.
      13.2 (9-25) ng/ml, P < 0.01), indicating increased glycocalyx degradation.
      CONCLUSION: Overall, RBC transfusion was associated with reduced coagulability
      and endothelial glycocalyx degradation. Transfusion of older RBCs was however
      associated with increased coagulability. The changes observed were small to
      moderate and the clinical relevance of these findings should be investigated in
      larger studies.

PMID- 25754543
TI  - Letter to the editor--Homicides in Greece: trends and features.

PMID- 25754544
TI  - Letter to the editor--Consumption of levamisole in cocaine preparations.

PMID- 25754545
TI  - Commentary on: Gauriot R, Gunaratnam L, Moroni R, Reinikainen T, Corander R.
      Statistical challenges in the quantification of gunshot residue evidence. J
      Forensic Sci 2013;58(5);1149-55.

PMID- 25754546
TI  - Letter to the editor--The problem of caffeine consumption in the bodybuilding
      scene.

PMID- 25754548
TI  - Force-displacement measurements of earlywood bordered pits using a mesomechanical
      tester.
AB  - The elastic properties of pit membranes are reported to have important
      implications in understanding air-seeding phenomena in gymnosperms, and pit
      aspiration plays a large role in wood technological applications such as wood
      drying and preservative treatment. Here we present force-displacement
      measurements for pit membranes of circular bordered pits, collected on a
      mesomechanical testing system. The system consists of a quartz microprobe
      attached to a microforce sensor that is positioned and advanced with a
      micromanipulator mounted on an inverted microscope. Membrane displacement is
      measured from digital image analysis. Unaspirated pits from earlywood of never
      dried wood of Larix and Pinus and aspirated pits from earlywood of dried wood of
      Larix were tested to generate force-displacement curves up to the point of
      membrane failure. Two failure modes were observed: rupture or tearing of the pit
      membrane by the microprobe tip, and the stretching of the pit membrane until the
      torus was forced out of the pit chamber through the pit aperture without rupture,
      a condition we refer to as torus prolapse. 

PMID- 25754547
TI  - Familial clustering of breast and prostate cancer and risk of postmenopausal
      breast cancer in the Women's Health Initiative Study.
AB  - BACKGROUND: Evidence suggests that the risk of breast and prostate cancer is
      increased among those with a family history of the same disease and particularly
      among first-degree relatives. However, less is known about the relationship
      between breast and prostate cancer within families and particularly among
      minority populations. METHODS: Analyses of participants in the Women's Health
      Initiative observational cohort who were free of breast cancer at the time of
      their baseline examination were conducted. Subjects were followed for breast
      cancer through August 31, 2009. A Cox proportional hazards regression modeling
      approach was used to estimate the risk of breast cancer associated with a family
      history of prostate cancer, breast cancer, and both among first-degree relatives.
      RESULTS: There were 78,171 eligible participants, and 3506 breast cancer cases
      were diagnosed during the study period. A family history of prostate cancer was
      associated with a modest increase in breast cancer risk after adjustments for
      confounders (adjusted hazard ratio [aHR], 1.14; 95% confidence interval [CI],
      1.02-1.26). In a separate analysis examining the joint impact of both cancers, a
      family history of both breast and prostate cancer was associated with a 78%
      increase in breast cancer risk (aHR, 1.78; 95% CI, 1.45-2.19). Risk estimates
      associated with a family history of both breast and prostate cancer were higher
      among African American women (aHR, 2.34; 95% CI, 1.09-5.02) versus white women
      (aHR, 1.66; 95% CI, 1.33-2.08). CONCLUSIONS: These findings suggest that prostate
      cancer diagnosed among first-degree family members increases a woman's risk of
      developing breast cancer. Future studies are needed to determine the relative
      contributions of genes and a shared environment to the risk for both cancers.

PMID- 25754549
TI  - Pseudoseohaeicola caenipelagi gen. nov., sp. nov., isolated from a tidal flat.
AB  - A Gram-stain-negative, non-motile, aerobic and pleomorphic bacterium, designated
      BS-W13T, was isolated from a tidal flat on the South Sea, South Korea, and its
      taxonomic position was investigated using a polyphasic approach. Strain BS-W13T
      grew optimally at 25  degrees C, at pH 7.0-8.0 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 BS-W13T clustered with the type strain
      of Seohaeicola saemankumensis, showing the highest sequence similarity (95.96 %)
      to this strain. Strain BS-W13T exhibited 16S rRNA gene sequence similarity values
      of 95.95, 95.91, 95.72 and 95.68 % to the type strains of Sulfitobacter
      donghicola, Sulfitobacter porphyrae, Sulfitobacter mediterraneus and Roseobacter
      litoralis, respectively. Strain BS-W13T contained Q-10 as the predominant
      ubiquinone and C18 : 1omega7c as the major fatty acid. The polar lipid profile of
      strain BS-W13T, containing phosphatidylcholine, phosphatidylglycerol,
      phosphatidylethanolamine, one unidentified aminolipid and one unidentified lipid
      as major components, was distinguishable from those of some phylogenetically
      related taxa. The DNA G+C content of strain BS-W13T was 58.1 mol%. The
      phylogenetic data and differential chemotaxonomic and other phenotypic properties
      revealed that strain BS-W13T constitutes a novel genus and species within family
      Rhodobacteraceae of the class Alphaproteobacteria, for which the name
      Pseudoseohaeicola caenipelagi gen. nov., sp. nov. is proposed. The type strain is
      BS-W13T ( = KCTC 42349T = CECT 8724T).

PMID- 25754550
TI  - Marmoricola solisilvae sp. nov. and Marmoricola terrae sp. nov., isolated from
      soil and emended description of the genus Marmoricola.
AB  - Two strains of species of the genus Marmoricola, designated KIS18-7T and JOS5-1T,
      were isolated from soil samples in Korea. The 16S rRNA gene sequence of strain
      KIS18-7T showed highest similarities with Marmoricola scoriae Sco-D01T (97.8 %),
      Marmoricola aequoreus SST-45T (97.6 %) and Marmoricola aurantiacus BC 361T (97.3
      %), and strain JOS5-1T had highest sequence similarities with M. aequoreus SST
      45T (97.5 %) and Marmoricola bigeumensis MSL-05T (97.3 %). The sequence
      similarity between KIS18-7T and JOS5-1T was 98.1 %. Phylogenetic analysis showed
      that these strains grouped with species of the genus Marmoricola. The major fatty
      acids of strain KIS18-7T were iso-C16 : 0 and C17 : 1omega8c, and C17 : 1omega8c,
      C18 : 0 10-methyl (TBSA), C18 : 1omega9c, C17 : 0 10-methyl and C16 : 0 2-OH for
      strain JOS5-1T. Strain KIS18-7T contained the polar lipids,
      diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine,
      phosphatidylinositol and phosphatidylcholine, while strain JOS5-1T contained
      diphosphatidylglycerol, phosphatidylglycerol, phosphatidylinositol, one unknown
      aminolipid and two unknown phospholipids. The peptidoglycan of both strains
      contained ll-diaminopimelic acid as the diagnostic diamino acid and a single
      glycine residue as the interpeptide bridge (type A3gamma). The major menaquinone
      of both strains was MK-8(H4). The G+C contents of the DNA of strains KIS18-7T and
      JOS5-1T were 68.0 mol% and 62.9 mol%, respectively. These data demonstrate that
      strains KIS18-7T and JOS5-1T are representatives of two novel species of the
      genus Marmoricola, for which the names Marmoricola solisilvae sp. nov. (type
      strain KIS18-7T = KACC 17307T = DSM 27140T = NBRC 109601T) and Marmoricola terrae
      sp. nov. (type strain JOS5-1T = KACC 17308T = DSM 27141T = NBRC 109602T) are
      proposed.

PMID- 25754551
TI  - Bradyrhizobium erythrophlei sp. nov. and Bradyrhizobium ferriligni sp. nov.,
      isolated from effective nodules of Erythrophleum fordii.
AB  - Six slow-growing rhizobial strains isolated from effective nodules of
      Erythrophleum fordii were classified into the genus Bradyrhizobiumbased on their
      16S rRNA gene sequences. The results of multilocus sequence analysis of recA,
      glnII and gyrB genes and 16S-23S rRNA intergenic spacer (IGS) sequence phylogeny
      indicated that the six strains belonged to two novel species, represented by
      CCBAU 53325T and CCBAU 51502T, which were consistent with the results of DNA-DNA
      hybridization; CCBAU 53325T had 17.65-25.59 % relatedness and CCBAU 51502T had
      22.69-44.58 % relatedness with five closely related type strains, Bradyrhizobium
      elkanii USDA 76T, B. pachyrhizi LMG 24246T, B. lablabi CCBAU 23086T, B. jicamae
      LMG 24556T and B. japonicum USDA 6T. In addition, analysis of phenotypic
      characteristics and fatty acid profiles also distinguished the test strains from
      defined species of Bradyrhizobium. Two novel species, Bradyrhizobium erythrophlei
      sp. nov., represented by the type strain CCBAU 53325T ( = HAMBI 3614T = CGMCC
      1.13002T = LMG 28425T), and Bradyrhizobium ferriligni sp. nov., represented by
      the type strain CCBAU 51502T ( = HAMBI 3613T = CGMCC 1.13001T), are proposed to
      accommodate the strains.

PMID- 25754552
TI  - Increased risk of diabetes with statin treatment is associated with impaired
      insulin sensitivity and insulin secretion: a 6 year follow-up study of the METSIM
      cohort.
AB  - AIMS/HYPOTHESIS: The aim of this work was to investigate the mechanisms
      underlying the risk of type 2 diabetes associated with statin treatment in the
      population-based Metabolic Syndrome in Men (METSIM) cohort. METHODS: A total of
      8,749 non-diabetic participants, aged 45-73 years, were followed up for 5.9
      years. New diabetes was diagnosed in 625 men by means of an OGTT, HbA1c >=6.5%
      (48 mmol/mol) or glucose-lowering medication started during the follow-up.
      Insulin sensitivity and secretion were evaluated with OGTT-derived indices.
      RESULTS: Participants on statin treatment (N = 2,142) had a 46% increased risk of
      type 2 diabetes (adjusted HR 1.46 [95% CI 1.22, 1.74]). The risk was dose
      dependent for simvastatin and atorvastatin. Statin treatment significantly
      increased 2 h glucose (2hPG) and glucose AUC of an OGTT at follow-up, with a
      nominally significant increase in fasting plasma glucose (FPG). Insulin
      sensitivity was decreased by 24% and insulin secretion by 12% in individuals on
      statin treatment (at FPG and 2hPG <5.0 mmol/l) compared with individuals without
      statin treatment (p < 0.01). Decreases in insulin sensitivity and insulin
      secretion were dose dependent for simvastatin and atorvastatin.
      CONCLUSIONS/INTERPRETATION: Statin treatment increased the risk of type 2
      diabetes by 46%, attributable to decreases in insulin sensitivity and insulin
      secretion.

PMID- 25754553
TI  - In adipose tissue, increased mitochondrial emission of reactive oxygen species is
      important for short-term high-fat diet-induced insulin resistance in mice.
AB  - AIMS/HYPOTHESIS: Consuming a high-fat diet (HFD) induces insulin resistance in
      white adipose tissue (WAT) within 1 week. However, little is known about the
      initiating events. One potential mechanism that has remained largely unexplored
      is excessive mitochondrial emission of reactive oxygen species (ROS). METHODS: To
      determine the role of mitochondrial ROS emissions at the onset of insulin
      resistance, wild-type (WT) mice were placed on an HFD for 1 week. WAT insulin
      sensitivity and inflammation were assessed by western blot. In addition, we
      optimised/validated a method to determine ROS emissions in permeabilised WAT.
      RESULTS: An HFD for 1 week resulted in impaired insulin signalling, increased c
      Jun NH2-terminal kinase (JNK) phosphorylation and an increase in oxidative
      stress. These changes were associated with an increase in fatty-acid-mediated
      mitochondrial ROS emissions without any change in mitochondrial
      respiration/content. To determine that mitochondrial ROS causes insulin
      resistance, we used transgenic mice that express human catalase in mitochondria
      (MCAT) as a model of upregulated mitochondrial antioxidant enzyme capacity. MCAT
      mice displayed attenuated mitochondrial ROS emission, preserved insulin
      signalling and no inflammatory response following an HFD.
      CONCLUSIONS/INTERPRETATION: Findings from this study suggest that elevated
      mitochondrial ROS emission contributes to HFD-induced WAT insulin resistance.

PMID- 25754554
TI  - Ocular side-effects of topical corticosteroids: what a dermatologist needs to
      know.
AB  - Topical corticosteroids are used frequently in dermatology and atopic dermatitis
      without significant adverse effects. Though ocular diseases such as glaucoma and
      cataracts are known complications of systemic corticosteroids, the role of
      topical corticosteroids is limited to case reports. This review assesses the
      literature regarding topical steroids and their role in ocular diseases. There is
      evidence of harm to vision when potent topical corticosteroids are
      inappropriately used for prolonged periods to periorbital sites. There is no
      evidence to date that weak TCS to the face or potent TCS to areas other than the
      eyes results in ocular complications. Further research trials are required in
      this area. 

PMID- 25754555
TI  - How mobile are protons in the structure of dental glass ionomer cements?
AB  - The development of dental materials with improved properties and increased
      longevity can save costs and minimize discomfort for patients. Due to their good
      biocompatibility, glass ionomer cements are an interesting restorative option.
      However, these cements have limited mechanical strength to survive in the
      challenging oral environment. Therefore, a better understanding of the structure
      and hydration process of these cements can bring the necessary understanding to
      further developments. Neutrons and X-rays have been used to investigate the
      highly complex pore structure, as well as to assess the hydrogen mobility within
      these cements. Our findings suggest that the lower mechanical strength in glass
      ionomer cements results not only from the presence of pores, but also from the
      increased hydrogen mobility within the material. The relationship between
      microstructure, hydrogen mobility and strength brings insights into the
      material's durability, also demonstrating the need and opening the possibility
      for further research in these dental cements. 

PMID- 25754556
TI  - Novel p16 binding peptide development for p16-overexpressing cancer cell
      detection using phage display.
AB  - Protein p(16INK4a) (p16) is a well-known biomarker for diagnosis of human
      papillomavirus (HPV) related cancers. In this work, we identify novel p16 binding
      peptides by using phage display selection method. A random heptamer phage display
      library was screened on purified recombinant p16 protein-coated plates to elute
      only the bound phages from p16 surfaces. Binding affinity of the bound phages was
      compared with each other by enzyme-linked immunosorbent assay (ELISA),
      fluorescence imaging technique, and bioinformatic computations. Binding
      specificity and binding selectivity of the best candidate phage-displayed p16
      binding peptide were evaluated by peptide blocking experiment in competition with
      p16 monoclonal antibody and fluorescence imaging technique, respectively. Five
      candidate phage-displayed peptides were isolated from the phage display selection
      method. All candidate p16 binding phages show better binding affinity than wild
      type phage in ELISA test, but only three of them can discriminate p16
      overexpressing cancer cell, CaSki, from normal uterine fibroblast cell, HUF, with
      relative fluorescence intensities from 2.6 to 4.2-fold greater than those of wild
      type phage. Bioinformatic results indicate that peptide 'Ser-His-Ser-Leu-Leu-Ser
      Ser' binds to p16 molecule with the best binding score and does not interfere
      with the common protein functions of p16. Peptide blocking experiment shows that
      the phage-displayed peptide 'Ser-His-Ser-Leu-Leu-Ser-Ser' can conceal p16 from
      monoclonal antibody interaction. This phage clone also selectively interacts with
      the p16 positive cell lines, and thus, it can be applied for p16-overexpressing
      cell detection.

PMID- 25754557
TI  - Early gene expression in Pseudomonas fluorescens exposed to a polymetallic
      solution.
AB  - The molecular response of Pseudomonas fluorescens cells exposed to a mixture of
      heavy metals remains largely unknown. Here, we studied the temporal changes in
      the early gene expression of P. fluorescens cells exposed to three doses of a
      polymetallic solution over two exposure times, through the application of a
      customized cDNA microarray. At the lowest metal dose (MD/4), we observed a
      repression of the Hsp70 chaperone system, MATE and MFS transporters, TonB
      membrane transporter and histidine kinases, together with an overexpression of
      metal transport (ChaC, CopC), chemotaxis and glutamine synthetase genes. At the
      intermediate metal dose (MD), several amino acid transporters, a response
      regulator (CheY), a TonB-dependent receptor and the mutT DNA repair gene were
      repressed; by contrast, an overexpression of genes associated with the
      antioxidative stress system and the transport of chelates and sulfur was
      observed. Finally, at the highest metal dose (4MD), a repression of genes
      encoding metal ion transporters, drug resistance and alginate biosynthesis was
      found, together with an overexpression of genes encoding antioxidative proteins,
      membrane transporters, ribosomal proteins, chaperones and proteases. It was
      concluded that P. fluorescens cells showed, over exposure time, a highly complex
      molecular response when exposed to a polymetallic solution, involving mechanisms
      related with chemotaxis, signal transmission, membrane transport, cellular redox
      state, and the regulation of transcription and ribosomal activity. 

PMID- 25754558
TI  - The efficacy of minocycline in inflammatory dermatoses: a case of prurigo
      pigmentosa of prepubescent onset in Western world.
AB  - We present a 21-year-old Italian girl with an 8-year history of missed diagnosed
      prurigo pigmentosa (PP) successfully treated with short monotherapy with
      minocycline. PP is an inflammatory disease characterized by recurrent pruritic
      erythematous papules followed by reticular hyperpigmentation usually located on
      the trunk. About 300 cases of PP have been described mainly in Japan, whereas
      only few cases have been reported in Italy. This report shows that minocycline is
      rapidly effective probably through its ability to scavenge reactive oxygen
      species and to inhibit the chemotaxis and neutrophil function. Other than its
      ethnic rarity, this case is very interesting because it is the third case of PP
      in Caucasian patient with prepubescent onset. 

PMID- 25754559
TI  - Theoretical investigation of quadrupole contributions to surface sum-frequency
      vibrational spectroscopy.
AB  - We study the effect of electric transition quadrupole moments on surface sum
      frequency vibrational spectroscopy (SFVS). The SSP, PPP and SPS effective sum
      frequency susceptibilities are derived from the nonzero macroscopic
      susceptibility tensors and related to molecular quadrupole polarizabilities.
      Using time-dependent density functional theory, we calculate the quadrupole
      susceptibilities of R-limonene liquids for the first time. The results indicate
      that quadrupole contributions have a significant influence on SFVS transmitted
      signals in the SPS polarization combination. We also suggest that the SPS spectra
      may be used as a general technique for detecting electric transition quadrupole
      moments. 

PMID- 25754560
TI  - Implementation research: an imperative for improving global health and health
      inequities.

PMID- 25754561
TI  - Appraising the evidence for public health policy components using the quality and
      impact of component evidence assessment.
AB  - An essential strategy expected to reduce the global burden of chronic and
      cardiovascular disease is evidence-based policy. However, it is often unknown
      what specific components should constitute an evidence-based policy intervention.
      We have developed an expedient method to appraise and compare the strengths of
      the evidence bases suggesting that individual components of a policy intervention
      will contribute to the positive public health impact of that intervention. Using
      a new definition of "best available evidence," the Quality and Impact of
      Component (QuIC) Evidence Assessment analyzes dimensions of evidence quality and
      evidence of public health impact to categorize multiple policy component evidence
      bases along a continuum of "emerging," "promising impact," "promising quality,"
      and "best." QuIC was recently applied to components from 2 policy interventions
      to prevent and improve the outcomes of cardiovascular disease: public-access
      defibrillation and community health workers. Results illustrate QuIC's utility in
      international policy practice and research. 

PMID- 25754563
TI  - Challenges and opportunities for implementation of interventions to prevent and
      control CVD in low-resource settings: a report from CESCAS in Argentina.
AB  - In Argentina, cardiovascular diseases cause an estimated 100,000 deaths and more
      than 250,000 coronary heart disease and stroke events annually, at a cost of more
      than $1 billion international dollars. Despite progress in the implementation of
      several programs to combat noncommunicable diseases in Argentina over the past
      few years, most health resources are still dedicated to infectious diseases and
      maternal and child health. The Institute for Clinical Effectiveness and Health
      Policy, an independent academic institution affiliated with the University of
      Buenos Aires medical school, runs the South American Centre of Excellence in
      Cardiovascular Health (CESCAS), a center devoted to epidemiology, implementation,
      and policy research. At the CESCAS, there are 3 ongoing randomized clinical
      trials focused on implementation science: 1) a mobile health intervention, for
      preventing the progression of prehypertension in low-income, urban settings in
      Argentina, Guatemala, and Peru; 2) a comprehensive approach to preventing and
      controlling hypertension in low-resource settings in Argentina; and 3) an
      educational approach to improving physicians' effectiveness in the detection,
      treatment, and control of hypercholesterolemia and high cardiovascular disease
      risk in low-resource settings in Argentina. All of these trials involve the
      design and implementation of complex interventions for changing the behaviors of
      providers and patients. The rationale of each of the 3 studies, the design of the
      interventions, and the evaluation of processes and outcomes are described in this
      article, together with the barriers and enabling factors associated with
      implementation-research studies. There is a strong need in Argentina and all of
      Latin America for building the health-research capacity and infrastructure
      necessary for undertaking implementation studies that will translate evidence
      from research findings into improvements in health policy and practice with
      regard to cardiovascular diseases and their risk factors. 

PMID- 25754562
TI  - Building a platform for translational research in chronic noncommunicable
      diseases to address population health: lessons from NHLBI supported CRONICAS in
      Peru.
AB  - The CRONICAS Centre of Excellence in Chronic Diseases, based at Universidad
      Peruana Cayetano Heredia, was created in 2009 with support from the U.S. National
      Heart, Lung, and Blood Institute (NHLBI). The vision of CRONICAS is to build a
      globally recognized center of excellence conducting quality and innovative
      research and generating high-impact evidence for health. The center's identity is
      embedded in its core values: generosity, innovation, integrity, and quality. This
      review has been structured to describe the development of the CRONICAS Centre,
      with a focus on highlighting the ongoing translational research projects and
      capacity-building strategies. The CRONICAS Centre of Excellence is not a risk
      averse organization: it benefits from past experiences, including past mistakes,
      and improves upon them and thus challenges traditional research approaches. This
      ethos and environment are key to fostering innovation in research. 

PMID- 25754564
TI  - Implementation of management strategies for diabetes and hypertension: from local
      to global health in cardiovascular diseases.
AB  - Diabetes and hypertension are chronic conditions that are growing in prevalence
      as major causal factors of cardiovascular disease (CVD). The need for chronic
      illness surveillance, population-risk management, and successful treatment
      interventions are crucial for reducing the burden of future CVD. Addressing these
      problems will require population-risk stratification, task-sharing and -shifting,
      and community-as well as network-based care. Information technology tools also
      provide new opportunities for identifying those at risk and for implementing
      comprehensive approaches to achieving the goal of improved health locally,
      regionally, nationally, and globally. This article discusses ongoing efforts at
      one university health center in the implementation of management strategies for
      diabetes and hypertension at the local, regional, national, and global levels. 

PMID- 25754565
TI  - Training and supervision of community health workers conducting population-based,
      noninvasive screening for CVD in LMIC: implications for scaling up.
AB  - BACKGROUND: Community health workers (CHW) can screen for cardiovascular disease
      risk as well as health professionals using a noninvasive screening tool. However,
      this demonstrated success does not guarantee effective scaling of the
      intervention to a population level. OBJECTIVES: This study sought to report
      lessons learned from supervisors' experiences monitoring CHW and perceptions of
      other stakeholders regarding features for successful scaling of interventions
      that incorporate task-sharing with CHW. METHODS: We conducted a qualitative
      analysis of in-depth interviews to explore stakeholder perceptions. Data was
      collected through interviews of 36 supervisors and administrators at
      nongovernmental organizations contracted to deliver and manage primary care
      services using CHW, directors, and staff at the government health care clinics,
      and officials from the departments of health responsible for the implementation
      of health policy. RESULTS: CHW are recognized for their value in offsetting
      severe human resource shortages and for their expert community knowledge. There
      is a lack of clear definitions for roles, expectations, and career paths for CHW.
      Formal evaluation and supervisory systems are highly desirable but nonexistent or
      poorly implemented, creating a critical deficit for effective implementation of
      programs using task-sharing. There is acknowledgment of environmental challenges
      (e.g., safety) and systemic challenges (e.g., respect from trained health
      professionals) that hamper the effectiveness of CHW. The government-community
      relationships presumed to form the basis of redesigned health care services have
      to be supported more explicitly and consistently on both sides in order to
      increase the acceptability of CHW and their effectiveness. CONCLUSIONS: The
      criteria critical for successful scaling of CHW-led screening are consistent with
      evidence for scaling-up communicable disease programs. Policy makers have to
      commit appropriate levels of resources and political will to ensure successful
      scaling of this intervention.

PMID- 25754566
TI  - The training and fieldwork experiences of community health workers conducting
      population-based, noninvasive screening for CVD in LMIC.
AB  - BACKGROUND: Cardiovascular disease (CVD) is on the rise in low- and middle-income
      countries and is proving difficult to combat due to the emphasis on improving
      outcomes in maternal and child health and infectious diseases against a backdrop
      of severe human resource and infrastructure constraints. Effective task-sharing
      from physicians or nurses to community health workers (CHW) to conduct population
      based screening for persons at risk has the potential to mitigate the impact of
      CVD on vulnerable populations. CHW in Bangladesh, Guatemala, Mexico, and South
      Africa were trained to conduct noninvasive population-based screening for persons
      at high risk for CVD. OBJECTIVES: This study sought to quantitatively assess the
      performance of CHW during training and to qualitatively capture their training
      and fieldwork experiences while conducting noninvasive screening for CVD risk in
      their communities. METHODS: Written tests were used to assess CHW's acquisition
      of content knowledge during training, and focus group discussions were conducted
      to capture their training and fieldwork experiences. RESULTS: Training was
      effective at increasing the CHW's content knowledge of CVD, and this knowledge
      was largely retained up to 6 months after the completion of fieldwork. Common
      themes that need to be addressed when designing task-sharing with CHW in chronic
      diseases are identified, including language, respect, and compensation. The
      importance of having intimate knowledge of the community receiving services from
      design to implementation is underscored. CONCLUSIONS: Effective training for
      screening for CVD in community settings should have a strong didactic core that
      is supplemented with culture-specific adaptations in the delivery of instruction.
      The incorporation of expert and intimate knowledge of the communities themselves
      is critical, from the design to implementation phases of training. Challenges
      such as role definition, defining career paths, and providing adequate
      remuneration must be addressed.

PMID- 25754567
TI  - Changes in health behaviors and self-rated health of participants in Meta Salud:
      a primary prevention intervention of NCD in Mexico.
AB  - BACKGROUND: Meta Salud was a community health worker-facilitated intervention for
      the prevention of noncommunicable diseases in Northern Mexico. OBJECTIVES: This
      analysis examined changes in perceived health, eating habits, and physical
      activity immediately and 3 months after the intervention. The impact on the
      resulting behavioral and psychological factors are reported. METHODS: This was a
      nonrandomized intervention study with 1 baseline and 2 post-intervention follow
      ups. Outcome evaluation consisted of anthropometric measurements, laboratory
      tests, and a lifestyle questionnaire. RESULTS: The most consistent patterns were
      increases in metabolic equivalent of task values expended per day from baseline
      to post-intervention (difference = 996; 95% confidence interval [CI]: 81 to
      1,912) and to 3-month follow-up (difference = 1,073; 95% CI: 119 to 2,028);
      greater likelihood of meeting Centers for Disease Control and Prevention daily
      exercise recommendations, with an increase from 49% to 60% at post-intervention
      (OR: 1.6, 95% CI: 1.0 to 2.4) and 63% at follow-up (OR: 1.7, 95% CI: 1.7 to 2.7);
      lesser likelihood for consuming whole milk, from 38% to 59% (OR: 2.9, 95% CI: 1.8
      to 4.7); fewer daily servings of packaged foods, from 0.72 to 0.57 (difference = 
      0.16; 95% CI: -0.28 to -0.03); fewer days of poor mental health, from 9.3 to 5.8
      (difference = -3.4; 95% CI: -5.1 to -1.7); and greater likelihood for reporting
      good self-rated health, from 41% to 54% post-intervention (OR: 2.1, 95% CI: 1.3
      to 3.6) and 57% at follow-up (OR: 2.5, 95% CI: 1.5 to 4.4). Changes in other
      outcomes, although in the expected direction of association, were not
      statistically significant. CONCLUSIONS: The study identified important strategies
      for making feasible dietary changes in the consumption of whole milk, sugary
      drinks, and packaged foods, yet there is still a need to identify strategies for
      improving consumption of healthy foods. There was stronger evidence for ways of
      improving physical activity as opposed to other outcome measures. Overall, it
      highlights the importance of behavioral and psychosocial factors as key
      intervention targets in preventing noncommunicable diseases in low- and middle
      income countries.

PMID- 25754568
TI  - A qualitative examination of secondary prophylaxis in rheumatic heart disease:
      factors influencing adherence to secondary prophylaxis in Uganda.
AB  - BACKGROUND: Rheumatic heart disease (RHD) is the most common cause of heart
      disease among Ugandans age 15 to 49 years. Secondary prophylaxis with monthly
      injection of benzathine penicillin is effective in preventing recurrence of acute
      rheumatic fever and worsening of RHD, but adherence rates are poor in Uganda.
      OBJECTIVES: This study sought to identify health behaviors, attitudes, and health
      care system factors that influence adherence to RHD secondary prophylaxis.
      METHODS: We conducted 5 structured focus groups with 36 participants on monthly
      penicillin injections for RHD in Kamplala, Uganda. Transcripts were analyzed
      using qualitative description analysis and health behavior models. RESULTS: Most
      participants were female (64%), from an urban area (81%), and had family income
      less than US$1 daily (69%). Ages ranged from 14 to 58 years. Median prophylaxis
      duration was 1.42 years and 58% were adherent (>=80% of injections). Key
      facilitators include perceived worsening of disease with missing injections,
      personal motivation, a reminder system for injections, supportive family and
      friends, and a positive relationship with health care providers. Barriers to
      adherence include lack of resources for transportation and medications, fear of
      injection pain, poor patient-provider communication, and poor availability of
      clinics and providers able to give injections. CONCLUSIONS: We identified key
      facilitators and barriers to secondary prophylaxis for RHD from the patient
      perspective framed within the socioecological model. Our findings provide
      direction for intervention development to improve national RHD secondary
      prophylaxis.

PMID- 25754569
TI  - Cardiovascular disease research and the development agenda in low- and middle
      income countries.

PMID- 25754570
TI  - The 5 * 5 path toward rheumatic heart disease control: outcomes from the Third
      Rheumatic Heart Disease forum.

PMID- 25754571
TI  - Rheumatic heart disease: Tools for Implementing Programmes.

PMID- 25754572
TI  - Diagnostic criteria in rheumatic heart disease.

PMID- 25754573
TI  - Childhood nutrition and prevention of rheumatic fever.

PMID- 25754574
TI  - RHD prevention perspectives in Bangladesh.

PMID- 25754575
TI  - A global health strategy to capitalize on proven-effective interventions for
      heart, lung, and blood diseases.

PMID- 25754576
TI  - Persistent headache in patients with multiple sclerosis starting treatment with
      fingolimod.

PMID- 25754577
TI  - Inter- and intra-domain horizontal gene transfer, gain-loss asymmetry and
      positive selection mark the evolutionary history of the CBM14 family.
AB  - Protein-carbohydrate interactions are ubiquitous in nature and at the core of
      many physiological processes of profound importance to health and disease.
      Specificity in protein-carbohydrate interactions is conferred by carbohydrate
      binding modules (CBMs) that can accurately discriminate among the multitude of
      saccharides found in nature, thus targeting proteins to their particular
      substrates. Family 14 carbohydrate-binding modules (CBM14s), more specifically,
      are short modules that bind explicitly to chitin, the second most abundant
      carbohydrate in nature. Although considerable effort has been placed in
      elucidating protein-carbohydrate interactions at the molecular level for
      biological and biotechnological applications, in contrast the evolutionary
      relationships among these modules are minimally understood. Using the CBM14
      family as an example, here we describe one of the first global molecular
      evolutionary analyses of a CBM family across all domains of life, with an
      emphasis on its origin, taxonomic distribution and pattern of diversification as
      a result of gene and module duplication, and positive selection. Our genome-wide
      searches recovered an impressive number of CBM14s from diverse lineages across
      nearly all domains of life. However, their highly disseminated distribution in
      taxa outside the Opisthokonta group strongly suggests a later evolutionary origin
      and elevated rates of inter- and intra-domain horizontal gene transfer. Moreover,
      accelerated rates of asymmetric gains and losses reveal a dynamic mode of birth
      and-death evolution, whereas positive selection acting on paralogous CBM14
      containing proteins suggest changes in substrate specificity and an increase in
      the functional promiscuity of this ancient CBM family. The importance of these
      results is discussed. 

PMID- 25754578
TI  - Everolimus maintenance in patients with mantle cell lymphoma not eligible for
      intensive therapy: results of a prematurely closed phase 2 study.

PMID- 25754580
TI  - Fluorescence in situ hybridization of TP53 for the detection of chromosome 17
      abnormalities in myelodysplastic syndromes.
AB  - Conventional G-banding cytogenetics (CC) detects chromosome 17 (chr17)
      abnormalities in 2% of patients with de novo myelodysplastic syndromes (MDS). We
      used CC and fluorescence in situ hybridization (FISH) (LSI p53/17p13.1) to assess
      deletion of 17p in 531 patients with de novo MDS from the Spanish Group of
      Hematological Cytogenetics. FISH detected - 17 or 17p abnormalities in 13 cases
      (2.6%) in whom no 17p abnormalities were revealed by CC: 0.9% of patients with a
      normal karyotype, 0% in non-informative cytogenetics, 50% of patients with a
      chr17 abnormality without loss of 17p and 4.7% of cases with an abnormal
      karyotype not involving chr17. Our results suggest that applying FISH of 17p13 to
      identify the number of copies of the TP53 gene could be beneficial in patients
      with a complex karyotype. We recommend using FISH of 17p13 in young patients with
      a normal karyotype or non-informative cytogenetics, and always in isolated
      del(17p). 

PMID- 25754579
TI  - Phase I study of the anti-CD74 monoclonal antibody milatuzumab (hLL1) in patients
      with previously treated B-cell lymphomas.
AB  - Milatuzumab (hLL1), a humanized anti-CD74 monoclonal antibody, has activity in
      preclinical non-Hodgkin lymphoma (NHL) models. We conducted a phase 1 trial in
      previously treated B-cell malignancies. Dose escalation included four planned
      dose levels (1.5, 4, 6 and 8 mg/kg) with milatuzumab given twice weekly for 6
      weeks. After dose level 1, the schedule was changed to daily (Monday-Friday) for
      10 days. Twenty-two patients were treated. The most common possibly related
      toxicities were infusion reaction, anemia, lymphopenia, neutropenia and
      thrombocytopenia. Three patients experienced dose-limiting toxicity (neutropenia,
      neutropenia, rash) at dose levels 1, 2 and 4, respectively. Eight patients had
      stable disease, with no objective responses. The serum half-life of milatuzumab
      was ~2 h. In seven patients, In-111 imaging showed no clear evidence of tumor
      targeting. The short half-life may reflect CD74 rapid internalization and
      presence on extratumoral tissues; this antigen sink must be overcome to
      capitalize on the promising preclinical activity of the drug.

PMID- 25754581
TI  - Progesterone Inhibits Endothelial Cell Migration Through Suppression of the Rho
      Activity Mediated by cSrc Activation.
AB  - We previously showed that progesterone (P4) could inhibit the proliferation of
      human umbilical venous endothelial cells (HUVECs) through the p53-dependent
      pathway. In the present study, we further demonstrated that P4 at physiologic
      levels (5-500 nM) concentration-dependently inhibited migration of HUVECs. This
      effect was blocked by pre-treatment with the P4 receptor (PR) agonist-antagonist,
      RU486, suggesting that the P4-induced migration inhibition in HUVECs was through
      the PR-mediated signaling pathway. Western blot analyses demonstrated that the
      levels of RhoA and Rac-1 protein were reduced in the P4-treated HUVECs. P4 also
      inhibited the membrane translocation of RhoA and Rac-1 protein. Moreover, the P4
      induced migration inhibition in HUVECs was prevented by over-expression of the
      constitutively active RhoA construct (RhoA V14). However, pre-treatment with the
      ROCK (a kinase associated with RhoA for transducing RhoA signaling) inhibitor,
      Y27632, abolished the over-expression of RhoA-induced prevention effect on the P4
      induced migration inhibition in HUVECs. These data suggest that the inhibition of
      Rho GTPases might account for the P4-induced migration inhibition of HUVECs. Pre
      treatment with the cSrc inhibitor, PP2, prevented the P4-induced migration
      inhibition in HUVEC. The levels of phosphorylated focal adhesion kinase (FAK) and
      paxillin protein were also decreased by P4 treatment. Taken together, these
      results suggest that suppression of the Rho-mediated pathway might be involved in
      the signal transduction leading to the inhibition of cell migration caused by P4
      in HUVECs.

PMID- 25754582
TI  - Performance of growing cattle on poor-quality rangelands supplemented with farm
      formulated protein supplements in Zimbabwe.
AB  - Farmers use different non-conventional protein supplements and different feeding
      strategies to aid their animals survive the dry season in Zimbabwe. The
      strategies can be giving supplements once a week or once every other day up to
      very little supplement daily. Supplements are either legume crop residues or
      forage legumes. However, the efficacy of the use of non-conventional protein
      supplements in promoting growth and at the same time lowering the age at first
      calving is little understood. The study tested whether supplementing with farm
      formulated non-conventional feeds could reduce live weight loss during the dry
      season and promote live weight gain as well as early development of sexual
      maturity in beef cattle. In a completely randomized design, thirty dams with
      calves on hooves were allocated to five different treatments which were repeated
      during the dry season for 3 years. The 3-year study results show that weight loss
      can be controlled, resulting in positive growth in both the pre-weaning and post
      weaning phases of growing cattle. Yearlings fed solely on natural pasture lost
      significant weight during the dry season as compared to supplemented groups. The
      period to puberty and first calving was achieved at 18 and 27 months,
      respectively. Using non-conventional protein supplements could thus improve
      livestock productivity in resource-poor farming communities. It was concluded
      that smallholder farmers can supplement cattle with a kilogram per day of low
      cost farm-based non-conventional legume meal to improve livestock productivity in
      semi-arid regions of Zimbabwe.

PMID- 25754583
TI  - Understanding the meaning of words and sentences: the role of non-linguistic
      processes.

PMID- 25754584
TI  - Measurements of electrical and mechanical dyssynchrony are both essential to
      improve prediction of CRT response.
AB  - INTRODUCTION: Predicting reverse remodeling after cardiac resynchronization
      therapy (CRT) remains challenging and different etiologies of heart failure might
      hamper identification of predictors. OBJECTIVE: Assess the incremental value of
      mechanical dyssynchrony besides electrical dyssynchrony for predicting CRT
      response. METHODS: 227 patients (51% ischemic) received CRT. Response was defined
      as >=15% left ventricular end systolic volume decrease after six months.
      Prediction models were developed comprising clinical parameters and electrical
      dyssynchrony (Model A), subsequently complemented with mechanical dyssynchrony
      (Model B). Models were compared by area under the receiver-operating curve (AUC),
      net reclassification index (NRI) and integrated discrimination improvement (IDI)
      for the complete cohort, ischemic (ICM) and non-ischemic (NICM) subpopulations.
      RESULTS: Model B performed significantly better than Model A supported by AUC,
      NRI and IDI. Furthermore, model B significantly better predicted response for
      NICM than ICM. CONCLUSION: Electrical dyssynchrony and mechanical dyssynchrony
      are essential to predict CRT response. Nevertheless, response prediction for ICM
      remains challenging.

PMID- 25754585
TI  - Generation and identification of anti-inflammatory peptides from bovine beta
      casein using enzyme preparations from cod and hog.
AB  - BACKGROUND: The aim of the present study was to generate and identify potential
      anti-inflammatory peptides from bovine beta-casein with enzyme preparations from
      cod and hog. Furthermore, the potential of cod trypsin, derived from fishery by
      products, to produce these bioactive peptides for replacement of non-food-grade
      tosyl phenylalanyl chloromethyl ketone (TPCK)-treated porcine trypsin enzyme
      preparation was evaluated. RESULTS: Potential anti-inflammatory peptides were
      obtained by hydrolysis of beta-casein with the tryptic enzyme preparations cod
      trypsin, porcine trypsin (TPCK-treated) and a porcine trypsin and chymotrypsin
      preparation (PTN 6.0 S). Proteolysates generated with enzyme preparations
      containing mainly chymotryptic activity (Cryotin, Cryotin F) did not exhibit any
      effect. CONCLUSION: The more chymotryptic enzyme activity is present, the lower
      is the potential anti-inflammatory activity of the hydrolysates in HEK(nfkappab
      RE) cells. Comparable peptides were produced by application of porcine trypsin
      (TPCK) and cod trypsin. Therefore, the enzyme preparation cod trypsin can replace
      the non-food-grade porcine enzyme preparation trypsin (TPCK) for the generation
      of potential anti-inflammatory peptides from beta-casein.

PMID- 25754586
TI  - The association between cognitive impairment and community service use patterns
      in older people living in Australia.
AB  - Family plays a vital role in supporting individuals with dementia to reside in
      the community, thus delaying institutionalisation. Existing research indicates
      that the burden of care-giving is particularly high for those caring for a person
      with dementia. Yet, little is known about the uptake of community services by
      people with a diagnosis of dementia. Therefore, this study aims to better
      understand the relationship between cognitive impairment and the receipt of
      community care services. In order to examine the relationship, secondary data
      collected across Queensland, Australia, from 59,352 home-care clients aged 65 and
      over during 2007-2008 are analysed. This cross-sectional study uses regression
      analyses to estimate the relationship between cognitive impairment and service
      mix, while controlling for socio-demographic characteristics. The dependent
      variables include formal services, informal care and total home-care service
      hours during a 12-month period. The findings of this study demonstrate that
      cognitive impairment is associated with accessing more hours of respite and day
      centre care but fewer hours of other formal care services. Additionally, the
      likelihood of support from an informal caregiver increases when a client becomes
      cognitively impaired. Therefore, this study demonstrates that there is an
      increased need for respite programmes to support informal caregivers in the
      future, as the population of people living with dementia increases. These
      findings support the need for investigations of new and innovative respite models
      in the future. 

PMID- 25754588
TI  - Editorial: 10 most accessed and the 10 most cited papers.

PMID- 25754587
TI  - Enhancement of cytotoxicity of artemisinin toward cancer cells by transferrin
      mediated carbon nanotubes nanoparticles.
AB  - Artemisinin (ART) is a kind of drug with an endoperoxide bridge which tends to
      react with Fe(2+) to generate radicals for killing cancer cells. However,
      simultaneous delivery of hydrophobic ART and Fe(2+) ions into cancer cells
      remains a major challenge. In this study, a multi-functional tumor-targeting drug
      delivery system employing hyaluronic acid-derivatized multi-walled carbon
      nanotubes (HA-MWCNTs) as drug carriers, transferrin (Tf) as targeting ligand and
      ART as a model drug for cancer treatment was constructed. This delivery system
      (HA-MWCNTs/Tf@ART) not only retained optical property of MWCNTs and cytotoxicity
      of ART but also demonstrated synergistic anti-tumor effect using ART and Tf.
      Compared with free ART, remarkably enhanced anti-tumor efficacy of this drug
      vehicle was realized both in cultured MCF-7 cells in vitro and in a tumor-bearing
      murine model in vivo, due to increased intracellular accumulation of ART and co
      delivery of Tf and ART analogs. HA-MWCNTs/Tf@ART with laser irradiation
      demonstrated the highest inhibition effect compared to the other groups. This
      result may provide a new way of using promising natural drugs for cancer therapy.

PMID- 25754589
TI  - A Prebiotic Chemistry Experiment on the Adsorption of Nucleic Acids Bases onto a
      Natural Zeolite.
AB  - There are currently few mechanisms that can explain how nucleic acid bases were
      synthesized, concentrated from dilute solutions, and/or protected against
      degradation by UV radiation or hydrolysis on the prebiotic Earth. A natural
      zeolite exhibited the potential to adsorb adenine, cytosine, thymine, and uracil
      over a range of pH, with greater adsorption of adenine and cytosine at acidic pH.
      Adsorption of all nucleic acid bases was decreased in artificial seawater
      compared to water, likely due to cation complexation. Furthermore, adsorption of
      adenine appeared to protect natural zeolite from thermal degradation. The C=O
      groups from thymine, cytosine and uracil appeared to assist the dissolution of
      the mineral while the NH2 group from adenine had no effect. As shown by FT-IR
      spectroscopy, adenine interacted with a natural zeolite through the NH2 group,
      and cytosine through the C=O group. A pseudo-second-order model best described
      the kinetics of adenine adsorption, which occurred faster in artificial
      seawaters.

PMID- 25754590
TI  - S-Isovaline Contained in Meteorites, Induces Enantiomeric Excess in D,L-glutamic
      Acid During Recrystallization.
AB  - S-Isovaline (S-Iva: 6.7 mmol) and D,L-glutamic acid (Glu: 2 mmol) were dissolved
      in 10 ml of hot water, and the resulting solution was divided in 5 vessels. After
      recrystallization, the crystals were collected from each vessel, and the
      enantiomeric excess (ee) of Glu was determined with chemical derivatization using
      1-fluoro-2,4-dinitrophenyl- 5-L-leucinamide followed by high-performance liquid
      chromatography. Ten crystallizations provided all D-rich Glu with ee values of
      2.69 % +/- 0.81% (mean +/- standard deviation), and those using R-Iva provided
      all L-rich Glu with ee values of 6.24 % +/- 2.20%. Five recrystallizations of D,L
      Glu alone provided ee values of 0.474 % +/- 0.33%. The differences among these
      three ee values were statistically significant, showing that S-Iva, which was
      present in meteorites caused a significant induction of ee in this physiological
      amino acid. This is the first outcome that S-Iva induced ee changes in a
      physiological amino acid. S-Iva did not induce any ee changes in D,L-asparagine,
      leucine, valine, methionine, phenylalanine, tryptophan, glutamine, tyrosine,
      aspartic acid, or histidine under similar recrystallizations.

PMID- 25754591
TI  - Template directed replication supports the maintenance of the metabolically
      coupled replicator system.
AB  - The RNA World scenario of prebiotic chemical evolution is among the most
      plausible conceptual framework available today for modelling the origin of life.
      RNA offers genetic and catalytic (metabolic) functionality embodied in a single
      chemical entity, and a metabolically cooperating community of RNA molecules would
      constitute a viable infrabiological subsystem with a potential to evolve into
      proto-cellular life. Our Metabolically Coupled Replicator System (MCRS) model is
      a spatially explicit computer simulation implementation of the RNA-World
      scenario, in which replicable ribozymes cooperate in supplying each other with
      monomers for their own replication. MCRS has been repeatedly demonstrated to be
      viable and evolvable, with different versions of the model improved in depth
      (chemical detail of metabolism) or in extension (additional functions of RNA
      molecules). One of the dynamically relevant extensions of the MCRS approach to
      prebiotic RNA evolution is the explicit inclusion of template replication into
      its assumptions, which we have studied in the present version. We found that this
      modification has not changed the behaviour of the system in the qualitative
      sense, just the range of the parameter space which is optimal for the coexistence
      of metabolically cooperating replicators has shifted in terms of metabolite
      mobility. The system also remains resistant and tolerant to parasitic
      replicators. 

PMID- 25754592
TI  - Paradoxes of early stages of evolution of life and biological complexity.
AB  - Two of the most fundamental questions concerning the origin of life, how
      biologically important molecules (RNA, proteins) find their unique spatial
      configuration, and how coding sequences can evolve beyond a certain critical
      length, are discussed. It is shown that both of these problems have not been
      solved. Experiments that could clarify the mechanisms of interaction between
      biologically important molecules in the simplest cells are discussed. 

PMID- 25754594
TI  - Loss-of-Function FANCL Mutations Associate with Severe Fanconi Anemia Overlapping
      the VACTERL Association.
AB  - The diagnosis of VACTERL syndrome can be elusive, especially in the prenatal
      life, due to the presence of malformations that overlap those present in other
      genetic conditions, including the Fanconi anemia (FA). We report on three VACTERL
      cases within two families, where the two who arrived to be born died shortly
      after birth due to severe organs' malformations. The suspicion of VACTERL
      association was based on prenatal ultrasound assessment and postnatal features.
      Subsequent chromosome breakage analysis suggested the diagnosis of FA. Finally,
      by next-generation sequencing based on the analysis of the exome in one family
      and of a panel of Fanconi genes in the second one, we identified novel FANCL
      truncating mutations in both families. We used ectopic expression of wild-type
      FANCL to functionally correct the cellular FA phenotype for both mutations. Our
      study emphasizes that the diagnosis of FA should be considered when VACTERL
      association is suspected. Furthermore, we show that loss-of-function mutations in
      FANCL result in a severe clinical phenotype characterized by early postnatal
      death. 

PMID- 25754595
TI  - When indomethacin fails: additional treatment options for "indomethacin
      responsive headaches".
AB  - Indomethacin has been used for the treatment of headache disorders since the
      1960's, shortly after it was introduced as a treatment for pain and joint
      swelling in rheumatologic conditions. A subgroup of primary headache disorders,
      often refractory to other pharmacologic treatment such as triptans and the usual
      non-steroidal anti-inflammatories, was noted to be exquisitely and absolutely
      responsive to the analgesic effects of indomethacin. These disorders have been
      better characterized over the past decade and classified into primary headache
      disorders of paroxysmal hemicrania (PH) and hemicrania continua (HC). Since the
      current ICHD-3 beta requires response to indomethacin as a diagnostic criterion,
      studies on alternative treatments in HC and PH generally occur in patients with
      intolerance to its gastro-intestinal side effects rather than loss of analgesia
      effectiveness. More rarely, the development of new headaches have been reported
      in chronic indomethacin use. In these settings, other classes of medications such
      as selective cyclooxygenase-2 inhibitors (celecoxib), anti-epileptic agents
      (topiramate), calcium channel blockers (verapamil, flunarizine), melatonin, and
      local nerve blocks with anesthetic and steroids have been shown to be effective
      in case reports and series. We review the literature and provide our clinical
      recommendations on alternative therapies for the "indomethacin-responsive
      headaches".

PMID- 25754596
TI  - TEV-48125: a review of a monoclonal CGRP antibody in development for the
      preventive treatment of migraine.
AB  - Calcitonin gene-related peptide (CGRP) is a 37-amino-acid neuropeptide whose
      involvement in migraine pathophysiology is well established. Originally migraine
      was believed to be a disease of the vasculature, but research has highlighted
      this to be a disease of the brain with CGRP playing an important role. While
      targeting CGRP using small molecule antagonists against the receptor has been
      effective, long-term use of these agents has not been possible due to safety
      concerns and/or formulation challenges. Recent advances in therapeutic antibodies
      have opened up new possibilities for treatment of migraine. TEV-48125 is one of
      four monoclonal antibodies targeting CGRP or its receptors, currently in
      development for the preventive treatment of migraine. This article discusses the
      in vitro and in vivo pharmacology of TEV-48125 as well as highlighting its safety
      profile through the six Phase 1 studies that have been conducted. Finally, the
      current state of development and future studies for TEV-48125 will be reviewed. 

PMID- 25754597
TI  - Headache in school children: is the prevalence increasing?
AB  - The objectives of this systematic review were to examine age dependency of
      headache prevalence in school age children and to assess secular trends of
      headache prevalence in the last decade, gender and regional differences. A
      literature search was performed in MEDLINE to identify all prevalence studies in
      children and adolescents. Five hundred seventy studies were found, of which 37
      studies could be included for this review. Headache prevalence in school children
      increases with their age as demonstrated in cohorts of identical children and
      cross-sectional surveys covering different age groups of children in one
      population. Regarding a potential general increase in the prevalence of headache
      in children and adolescents in the last decade, there are four studies which all
      show some increase of headache prevalence; however, the degree of increase is
      varying. Prevalence of headache in girls appears to be higher than in boys. There
      were no clear regional differences in the prevalence of headache. 

PMID- 25754598
TI  - Oral triptans in children and adolescents: an update.
AB  - This review evaluates the recent progress in clinical trials on oral triptans for
      acute migraine in children and adolescents. Randomized controlled trials (RCT) on
      the treatment of migraine in pediatric patients were rare and difficult to
      design. In particular, high placebo response in many of the trials made it
      difficult to prove efficacy of triptans. Using a "novel study design" for RCT, a
      study successfully proved the efficacy of an oral rizatriptan. This trial
      enrolled patients with unsatisfactory response to nonsteroidal anti-inflammatory
      or acetaminophen and with migraine lasting longer than 3 h. Rizatriptan was
      approved by Food and Drug Administration (FDA) (USA) for children and adolescents
      of 6-17 years. The triptan-NSAID combination drug for pediatric patients also
      showed efficacy.

PMID- 25754600
TI  - Headache as an emergency in children and adolescents.
AB  - Pediatric and adolescence headache is one of the most common causes of access in
      emergency departments (ED). Primary headache and headache secondary to self
      limited conditions are the majority of cases. Secondary life-threatening
      headaches are less frequent and may be recognized by a careful history and
      physical examination. The primary objective for ED physicians is to recognize the
      serious life-threatening conditions requiring immediate medical care among the
      wide spectrum of headache diagnoses. 

PMID- 25754601
TI  - Mastery-approach goals eliminate retrieval-induced forgetting: the role of
      achievement goals in memory inhibition.
AB  - The present study examined how achievement goals affect retrieval-induced
      forgetting. Researchers have suggested that mastery-approach goals (i.e.,
      developing one's own competence) promote a relational encoding, whereas
      performance-approach goals (i.e., demonstrating one's ability in comparison with
      others) promote item-specific encoding. These different encoding processes may
      affect the degree to which participants integrate the exemplars within a category
      and, as a result, we expected that retrieval-induced forgetting may be reduced or
      eliminated under mastery-approach goals. Three experiments were conducted using a
      retrieval-practice paradigm with different stimuli, where participants'
      achievement goals were manipulated through brief written instructions. A meta
      analysis that synthesized the results of the three experiments showed that
      retrieval-induced forgetting was not statistically significant in the mastery
      approach goal condition, whereas it was statistically significant in the
      performance-approach goal condition. These results suggest that mastery-approach
      goals eliminate retrieval-induced forgetting, but performance-approach goals do
      not, demonstrating that motivation factors can influence inhibition and
      forgetting. 

PMID- 25754599
TI  - Psychiatric comorbidity in childhood and adolescence headache.
AB  - Primary headaches among children and adolescents have a substantial impact on
      quality of life, daily activities, social interaction, and school performance in
      combination with psychopathological symptoms. The main purpose of the present
      paper is to summarize clinical and epidemiological evidence for psychiatric
      comorbidity among children and adolescents with headaches, to describe how
      evidence in headache research suggest different pathways involved in the
      development and maintenance of these comorbid conditions, and finally suggest
      some elements professionals may find helpful to assess the scope of complaints,
      related functional impairment, and potential precipitating factors in planning of
      more targeted treatments. 

PMID- 25754602
TI  - Cloning and characterization of a novel O-methyltransferase from Flammulina
      velutipes that catalyzes methylation of pyrocatechol and pyrogallol structures in
      polyphenols.
AB  - A novel O-methyltransferase gene was isolated from Flammulina velutipes. The
      isolated full-length cDNA was composed of a 690-nucleotide open reading frame
      encoding 230 amino acids. A database search revealed that the deduced amino acid
      sequence was similar to those of other O-methyltransferases; the highest identity
      was only 61.8% with Laccaria bicolor. The recombinant enzyme was expressed by
      Escherichia coli. BL21 (DE3) was assessed for its ability to methylate (-)
      epigallocatechin-3-O-gallate (EGCG). LC-TOF-MS and NMR revealed that the enzyme
      produced five kinds of O-methylated EGCGs: (-)-epigallocatechin-3-O-(3-O
      methyl)gallate, (-)-epigallocatechin-3-O-(4-O-methyl)gallate, (-)
      epigallocatechin-3-O-(3,4-O-dimethyl)gallate, (-)-epigallocatechin-3-O-(3,5-O
      dimethyl)gallate, and (-)-4'-O-methylepigallocatechin-3-O-(3,5-O
      dimethyl)gallate. The substrate specificity of the enzyme for 20 kinds of
      polyphenols was assessed using the crude recombinant enzyme of O
      methyltransferase. This enzyme introduced methyl group(s) into polyphenols with
      pyrocatechol and pyrogallol structures. 

PMID- 25754603
TI  - Editorial Comment to Feasibility and accuracy of computational robot-assisted
      partial nephrectomy planning by virtual partial nephrectomy analysis.

PMID- 25754604
TI  - Detection of fetal chromosomal anomalies: does nuchal translucency measurement
      have added value in the era of non-invasive prenatal testing?
AB  - OBJECTIVES: The objective of this study is to determine what percentage of fetal
      chromosomal anomalies remains undetected when first trimester combined testing is
      replaced by non-invasive prenatal testing for trisomies 13, 18, and 21. We
      focused on the added clinical value of nuchal translucency (NT) measurement.
      METHODS: Data on fetal karyotype, ultrasound findings, and pregnancy outcome of
      all pregnancies with an NT measurement >=3.5 mm were retrospectively collected
      from a cohort of 25,057 singleton pregnancies in which first trimester combined
      testing was performed. RESULTS: Two hundred twenty-five fetuses (0.9 %) had an NT
      >=3.5 mm. In 24 of these pregnancies, a chromosomal anomaly other than trisomy
      13, 18, or 21 was detected. Eleven resulted in fetal demise, and ten showed fetal
      ultrasound anomalies. In three fetuses with normal ultrasound findings, a
      chromosomal anomaly was detected, of which one was a triple X. CONCLUSIONS: In
      three out of 25,057 pregnancies (0.01%), non-invasive prenatal testing and fetal
      ultrasound would have missed a chromosomal anomaly that would have been
      identified by NT measurement. (c) 2015 John Wiley & Sons, Ltd.

PMID- 25754605
TI  - The coherence and correlates of intermittent explosive disorder amongst West
      Papuan refugees displaced to Papua New Guinea.
AB  - Questions remain about the nosological status of intermittent explosive disorder
      (IED) as a universal diagnosis. Cross-cultural studies are needed to establish
      whether IED symptoms form a coherent pattern and are distinguishable from other
      related symptom constellations. A study amongst a refugee population also allows
      further inquiry of the relationship between exposure to potentially traumatic
      events (PTEs) and other adversities with the IED constellation. In the present
      study amongst West Papuan refugees residing in Port Moresby, Papua New Guinea, we
      apply culturally adapted interview modules to assess symptoms of IED, post
      traumatic stress disorder (PTSD), and depression, as well as the potentially
      traumatic events (PTEs) of conflict and ongoing adversity in the post-migration
      environment. Latent class analysis yielded a PTSD class (23%), a posttraumatic
      depressive class (14%), an IED class (12%), and a low/no symptom class (49%).
      Compared to the low/no-symptom class, the PTSD class had high levels of exposure
      to all PTE domains including childhood-related adversities, witnessing murder,
      human rights trauma, and traumatic losses, as well as ongoing adversity relating
      to displacement and separation from families, safety concerns, and lack of access
      to basic needs and health care. The posttraumatic depression class had greater
      exposure to traumatic losses and childhood-related adversities, higher levels of
      stress relating to material loss and deprivation, as well as to displacement and
      separation from families. In contrast, the IED class was distinguished only by
      the ongoing stress of displacement and separation from families in the homeland.
      Our findings provide support for the phenomenological distinctiveness of IED
      symptoms in this transcultural setting. Although not exclusive to IED, conditions
      of long-term displacement and separation appear to be a source of ongoing anger
      and explosive aggression amongst this population. 

PMID- 25754607
TI  - Beyond biology: the biopsychosocial model and its application in obstetrics and
      gynaecology.

PMID- 25754606
TI  - Comparison of two instruments to track depression symptoms during pregnancy in a
      sample of pregnant teenagers in Southern Brazil.
AB  - INTRODUCTION: Depression during pregnancy in adolescents is increasing
      significantly. However, instruments for early depression screening during
      prenatal care are scarce. Faced this fact, the objective of this research is to
      identify the best cutoff points for the Edinburgh Postnatal Depression Scale
      (EPDS) and Beck Depression Inventory (BDI) in a sample of pregnant adolescents.
      METHOD: 807 pregnant adolescents, with a mean age of 17 years, met in public
      antenatal services were evaluated. Two screening scales for depression were
      analyzed, EPDS and the BDI. These scales had their accuracy measured by AUC of
      their ROC curve, as well as their respective sensitivity and specificity.
      RESULTS: In the analysis, the best cutoff for the EPDS was>=10, in which the
      sensitivity was 81.1% and specificity 82.7%. For the BDI, it was with recognized
      the cutoff >=11, sensitivity 86.7% and specificity 73.8%. In the analysis of the
      ROC AUC, values of 0.89 (CI 0.87-0.92) for the EPDS and BDI for 0.87 (CI 0.84
      0.89) were identified compared to the MINI. LIMITATIONS: The sample was composed
      majority by middle and low income adolescent and the study was performed only
      with pregnant women in the second trimester. CONCLUSIONS: The results indicate
      that both scales have good accuracy in screening of depression in adolescent
      mothers. However, the EPDS scale shows higher AUC ROC and also better sensitivity
      and specificity values, the latter being more precise and effective for screening
      for depression in this population.

PMID- 25754608
TI  - Competition for pollinators and intra-communal spectral dissimilarity of flowers.
AB  - Competition for pollinators occurs when, in a community of flowering plants,
      several simultaneously flowering plant species depend on the same pollinator.
      Competition for pollinators increases interspecific pollen transfer rates,
      thereby reducing the number of viable offspring. In order to decrease
      interspecific pollen transfer, plant species can distinguish themselves from
      competitors by having a divergent phenotype. Floral colour is an important
      signalling cue to attract potential pollinators and thus a major aspect of the
      flower phenotype. In this study, we analysed the amount of spectral dissimilarity
      of flowers among pollinator-competing plants in a Dutch nature reserve. We
      expected pollinator-competing plants to exhibit more spectral dissimilarity than
      non-competing plants. Using flower visitation data of 2 years, we determined the
      amount of competition for pollinators by different plant species. Plant species
      that were visited by the same pollinator were considered specialist and competing
      for that pollinator, whereas plant species visited by a broad array of
      pollinators were considered non-competing generalists. We used principal
      components analysis to quantify floral reflectance, and found evidence for
      enhanced spectral dissimilarity among plant species within specialist pollinator
      guilds (i.e. groups of plant species competing for the same pollinator). This is
      the first study that examined intra-communal dissimilarity in floral reflectance
      with a focus on the pollination system.

PMID- 25754609
TI  - Brown fat activation reduces hypercholesterolaemia and protects from
      atherosclerosis development.
AB  - Brown adipose tissue (BAT) combusts high amounts of fatty acids, thereby lowering
      plasma triglyceride levels and reducing obesity. However, the precise role of BAT
      in plasma cholesterol metabolism and atherosclerosis development remains unclear.
      Here we show that BAT activation by beta3-adrenergic receptor stimulation
      protects from atherosclerosis in hyperlipidemic APOE*3-Leiden.CETP mice, a well
      established model for human-like lipoprotein metabolism that unlike
      hyperlipidemic Apoe(-/-) and Ldlr(-/-) mice expresses functional apoE and LDLR.
      BAT activation increases energy expenditure and decreases plasma triglyceride and
      cholesterol levels. Mechanistically, we demonstrate that BAT activation enhances
      the selective uptake of fatty acids from triglyceride-rich lipoproteins into BAT,
      subsequently accelerating the hepatic clearance of the cholesterol-enriched
      remnants. These effects depend on a functional hepatic apoE-LDLR clearance
      pathway as BAT activation in Apoe(-/-) and Ldlr(-/-) mice does not attenuate
      hypercholesterolaemia and atherosclerosis. We conclude that activation of BAT is
      a powerful therapeutic avenue to ameliorate hyperlipidaemia and protect from
      atherosclerosis. 

PMID- 25754611
TI  - Clinicopathologic significance of BubR1 and Mad2 overexpression in oral cancer.
AB  - OBJECTIVES: BubR1 and Mad2 are central components of the mitotic checkpoint
      complex that inhibits anaphase onset until all chromosomes are correctly aligned
      at the metaphase plate. We propose to analyse the combined expression of BubR1
      and Mad2 and assess its significance to oral squamous cell carcinoma (OSCC)
      diagnosis and prognosis. MATERIALS AND METHODS: BubR1 and Mad2 expression was
      assessed by real-time PCR in OSCC cell lines and in normal human oral
      keratinocytes, and by immunohistochemistry in 65 patients with OSCC. The results
      were compared regarding clinicopathological parameters, proliferative activity
      and survival. RESULTS: BubR1 and Mad2 transcripts were overexpressed in OSCC cell
      lines which also exhibited attenuated spindle assembly checkpoint activity. BubR1
      and Mad2 were also overexpressed in patients with OSCC. BubR1 expression was
      associated with advanced stages and larger tumour size in univariate analysis,
      and with shorter overall survival both in univariate and multivariate analysis.
      Mad2 overexpression was associated with that of BubR1 and, importantly, high
      expression of Mad2 and BubR1 was associated with increased cellular
      proliferation. CONCLUSION: Our data propose a role for BubR1 and Mad2 in OSCC
      cellular proliferation, progression and prognosis.

PMID- 25754610
TI  - Antidepressants but not antipsychotics have antiepileptogenic effects with
      limited effects on comorbid depressive-like behaviour in the WAG/Rij rat model of
      absence epilepsy.
AB  - BACKGROUND AND PURPOSE: Two of the most relevant unmet needs in epilepsy are
      represented by the development of disease-modifying drugs able to affect
      epileptogenesis and/or the study of related neuropsychiatric comorbidities. No
      systematic study has investigated the effects of chronic treatment with
      antipsychotics or antidepressants on epileptogenesis. However, such drugs are
      known to influence seizure threshold. EXPERIMENTAL APPROACH: We evaluated the
      effects of an early long-term treatment (ELTT; 17 weeks), started before seizure
      onset (P45), with fluoxetine (selective 5-HT-reuptake inhibitor), duloxetine
      (dual-acting 5-HT-noradrenaline reuptake inhibitor), haloperidol (typical
      antipsychotic drug), risperidone and quetiapine (atypical antipsychotic drugs) on
      the development of absence seizures and comorbid depressive-like behaviour in the
      WAG/Rij rat model. Furthermore, we studied the effects of these drugs on
      established absence seizures in adult (6-month-old) rats after a chronic 7 weeks
      treatment. KEY RESULTS: ELTT with all antipsychotics did not affect the
      development of seizures, whereas, both ELTT haloperidol (1 mg . kg(-1) day(-1))
      and risperidone (0.5 mg . kg(-1) day(-1)) increased immobility time in the forced
      swimming test and increased absence seizures only in adult rats (7 weeks
      treatment). In contrast, both fluoxetine (30 mg . kg(-1) day(-1)) and duloxetine
      (10-30 mg . kg(-1) day(-1)) exhibited clear antiepileptogenic effects. Duloxetine
      decreased and fluoxetine increased absence seizures in adult rats. Duloxetine did
      not affect immobility time; fluoxetine 30 mg . kg(-1) day(-1) reduced immobility
      time while at 10 mg . kg(-1) day(-1) an increase was observed. CONCLUSIONS AND
      IMPLICATIONS: In this animal model, antipsychotics had no antiepileptogenic
      effects and might worsen depressive-like comorbidity, while antidepressants have
      potential antiepileptogenic effects even though they have limited effects on
      comorbid depressive-like behaviour.

PMID- 25754612
TI  - Expression of TCR-Vbeta peptides by murine bone marrow cells does not identify T
      cell progenitors.
AB  - Germline transcription has been described for both immunoglobulin and T-cell
      receptor (TCR) genes, raising questions of their functional significance during
      haematopoiesis. Previously, an immature murine T-cell line was shown to bind
      antibody to TCR-Vbeta8.2 in absence of anti-Cbeta antibody binding, and an
      equivalent cell subset was also identified in the mesenteric lymph node. Here, we
      investigate whether germline transcription and cell surface Vbeta8.2 expression
      could therefore represent a potential marker of T-cell progenitors. Cells with
      the TCR phenotype of Vbeta8.2(+) Cbeta(-) are found in several lymphoid sites,
      and among the lineage-negative (Lin(-)) fraction of hematopoietic progenitors in
      bone marrow (BM). Cell surface marker analysis of these cells identified subsets
      reflecting common lymphoid progenitors, common myeloid progenitors and
      multipotential progenitors. To assess whether the Lin(-) Vbeta8.2(+) Cbeta(-) BM
      subset contains hematopoietic progenitors, cells were sorted and adoptively
      transferred into sub-lethally irradiated recipients. No T-cell or myeloid progeny
      were detected following introduction of cells via the intrathymic or intravenous
      routes. However, B-cell development was detected in spleen. This pattern of
      restricted in vivo reconstitution disputes Lin(-) Vbeta8.2(+) Cbeta(-) BM cells
      as committed T-cell progenitors, but raises the possibility of progenitors with
      potential for B-cell development.

PMID- 25754613
TI  - Management of headache disorders in the Emergency Department setting.
AB  - Headache is a common presenting complaint in the Emergency Department. The aim of
      this study was to delineate the demographic profile of patients presenting a
      chief complaint of headache and to assess the application of diagnostic
      algorithms for the management of these patients. We examined patients admitted to
      the Spedali Civili Hospital ED between January 2005 and December 2009 who
      complained of headache not related to trauma and all patients hospitalized for
      headache in Neurological Clinic, from ED, between January 2008 and December 2009.
      7495 patients were examined at ED for headaches. 72 % of patients were
      discharged, 22 % were admitted. From 2005 to 2009, there was a definite decrease
      in the rate of hospitalization due to headache (15 vs 9.9 % in Department of
      Neurology and 26 vs 18.9 % in all Departments). Considering the decrease year by
      year, this reduction was significant from 2007 to 2008, when the algorithms were
      adopted. The most common diagnosis in the ED was "Non-specific headache" (41 %),
      followed by "Primary headaches and complications of primary headaches" (20.8 %),
      "Secondary headaches not associated with risk of serious disease" (20.4 %) and
      "Secondary headache associated with risk of serious disease" (5 %). Over 2-year
      period (2008-2009) we found an increase in the diagnosis of "Primary headaches
      and complications of primary headaches" and "Secondary headaches associated with
      risk of serious disease" compared with a decrease of "nonspecific headache" and
      "secondary headaches not associated with risk of serious disease". The use of the
      diagnostic algorithms and collaborative network between the ED and the Headache
      Center can improve the management of patients with headache in ED.

PMID- 25754614
TI  - Latitude has more significant impact on prevalence of multiple sclerosis than
      ultraviolet level or sunshine duration in Japanese population.
AB  - Higher latitude is known to be associated with higher prevalence of multiple
      sclerosis (MS). We investigated the degree of impact of latitude, ultraviolet
      (UV) radiation, and sunshine on the prevalence of MS in Japan, which has 47
      prefectures with a variety of climates. MS prevalence in each prefecture was
      collected from database of the Ministry of Health, Labour, and Welfare of Japan.
      Latitude of each prefecture was represented by that of the capital city. Data of
      UV radiation level and annual actual sunshine duration were obtained from
      databases of Japan Meteorological Agency. We performed linear correlation
      analyses of MS prevalence against latitude, UV radiation, and annual actual
      sunshine duration. MS prevalence significantly correlated to latitude (Pearson's
      correlation, r = 0.69, p < 0.001) and UV radiation level (r = -0.65, p < 0.001)
      but not to annual actual sunshine duration (r = -0.37, p = 0.011). Stepwise
      multiple linear regression analyses revealed significant correlation between MS
      prevalence and only latitude (p < 0.001). While our result shows that both
      latitude and the UV intensity have significant relationship to MS prevalence, the
      stronger relevance of the former suggests an existence of risk factors other than
      UV radiation.

PMID- 25754615
TI  - The post-disaster negative health legacy: pregnancy outcomes in Louisiana after
      Hurricane Andrew.
AB  - Disasters and displacement increasingly affect and challenge urban settings. How
      do pregnant women fare in the aftermath of a major disaster? This paper
      investigates the effect of pregnancies in disaster situations. The study tests a
      hypothesis that pregnant women residing in hurricane-prone areas suffer higher
      health risks. The setting is Louisiana in the Gulf Coast, United States, a state
      that continually experiences hurricane impacts. The time period for the analysis
      is three years following the landfall of Hurricane Andrew in 1992. We analysed
      low birth weight and preterm deliveries before and after landfall, as a whole and
      by race. Findings support an association between hazards and health of a
      community and indicate that pregnant women in the affected area, irrespective of
      race, are more likely to experience preterm deliveries compared to pre-event
      births. Results suggest there is a negative health legacy impact in Louisiana as
      a result of hurricane landfall. 

PMID- 25754616
TI  - D-psicose, an epimer of D-fructose, favorably alters lipid metabolism in Sprague
      Dawley rats.
AB  - D-Psicose, a C3 epimer of D-fructose, is known to lower body weight and adipose
      tissue weight and affect lipid metabolism. The precise mechanism remains unknown.
      It has been reported that D-psicose has a short half-life and is not metabolized
      in the body. To determine how D-psicose modifies lipid metabolism, rats were fed
      diets with or without 3% D-psicose for 4 weeks. Rats were decapitated without
      fasting every 6 h over a period of 24 h. Changes in serum and liver lipid levels,
      liver enzyme activity, and gene expression were quantified in experiment 1. Rats
      fed D-psicose had significantly lower serum insulin and leptin levels. Liver
      enzyme activities involved in lipogenesis were significantly lowered by the D
      psicose diet, whereas gene expression of a transcriptional modulator of fatty
      acid oxidation was enhanced. In experiment 2, feeding the D-psicose diet gave
      significantly lower body weight (389 +/- 3 vs 426 +/- 6 g, p < 0.05) and food
      intake (23.8 +/- 0.2 vs 25.7 +/- 0.4 g/day, p < 0.05) compared to the control
      diet. Rats fed the D-psicose diet gave significantly higher energy expenditure in
      the light period and fat oxidation in the dark period compared to rats fed the
      control diet, whereas carbohydrate oxidation was lower. In summary, these results
      indicate that the D-psicose diet decreases lipogenesis, increases fatty acid
      oxidation, and enhances 24 h energy expenditure, leading to d-psicose's potential
      for weight management.

PMID- 25754617
TI  - Hormone therapy for preventing cardiovascular disease in post-menopausal women.
AB  - BACKGROUND: Evidence from systematic reviews of observational studies suggests
      that hormone therapy may have beneficial effects in reducing the incidence of
      cardiovascular disease events in post-menopausal women, however the results of
      randomised controlled trials (RCTs) have had mixed results. This is an updated
      version of a Cochrane review published in 2013. OBJECTIVES: To assess the effects
      of hormone therapy for the prevention of cardiovascular disease in post
      menopausal women, and whether there are differential effects between use in
      primary or secondary prevention. Secondary aims were to undertake exploratory
      analyses to (i) assess the impact of time since menopause that treatment was
      commenced (>= 10 years versus < 10 years), and where these data were not
      available, use age of trial participants at baseline as a proxy (>= 60 years of
      age versus < 60 years of age); and (ii) assess the effects of length of time on
      treatment. SEARCH METHODS: We searched the following databases on 25 February
      2014: Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane
      Library, MEDLINE, EMBASE and LILACS. We also searched research and trials
      registers, and conducted reference checking of relevant studies and related
      systematic reviews to identify additional studies. SELECTION CRITERIA: RCTs of
      women comparing orally administered hormone therapy with placebo or a no
      treatment control, with a minimum of six months follow-up. DATA COLLECTION AND
      ANALYSIS: Two authors independently assessed study quality and extracted data. We
      calculated risk ratios (RRs) with 95% confidence intervals (CIs) for each
      outcome. We combined results using random effects meta-analyses, and undertook
      further analyses to assess the effects of treatment as primary or secondary
      prevention, and whether treatment was commenced more than or less than 10 years
      after menopause. MAIN RESULTS: We identified six new trials through this update.
      Therefore the review includes 19 trials with a total of 40,410 post-menopausal
      women. On the whole, study quality was good and generally at low risk of bias;
      the findings are dominated by the three largest trials. We found high quality
      evidence that hormone therapy in both primary and secondary prevention conferred
      no protective effects for all-cause mortality, cardiovascular death, non-fatal
      myocardial infarction, angina, or revascularisation. However, there was an
      increased risk of stroke in those in the hormone therapy arm for combined primary
      and secondary prevention (RR 1.24, 95% CI 1.10 to 1.41). Venous thromboembolic
      events were increased (RR 1.92, 95% CI 1.36 to 2.69), as were pulmonary emboli
      (RR 1.81, 95% CI 1.32 to 2.48) on hormone therapy relative to placebo.The
      absolute risk increase for stroke was 6 per 1000 women (number needed to treat
      for an additional harmful outcome (NNTH) = 165; mean length of follow-up: 4.21
      years (range: 2.0 to 7.1)); for venous thromboembolism 8 per 1000 women (NNTH =
      118; mean length of follow-up: 5.95 years (range: 1.0 to 7.1)); and for pulmonary
      embolism 4 per 1000 (NNTH = 242; mean length of follow-up: 3.13 years (range: 1.0
      to 7.1)).We performed subgroup analyses according to when treatment was started
      in relation to the menopause. Those who started hormone therapy less than 10
      years after the menopause had lower mortality (RR 0.70, 95% CI 0.52 to 0.95,
      moderate quality evidence) and coronary heart disease (composite of death from
      cardiovascular causes and non-fatal myocardial infarction) (RR 0.52, 95% CI 0.29
      to 0.96; moderate quality evidence), though they were still at increased risk of
      venous thromboembolism (RR 1.74, 95% CI 1.11 to 2.73, high quality evidence)
      compared to placebo or no treatment. There was no strong evidence of effect on
      risk of stroke in this group. In those who started treatment more than 10 years
      after the menopause there was high quality evidence that it had little effect on
      death or coronary heart disease between groups but there was an increased risk of
      stroke (RR 1.21, 95% CI 1.06 to 1.38, high quality evidence) and venous
      thromboembolism (RR 1.96, 95% CI 1.37 to 2.80, high quality evidence). AUTHORS'
      CONCLUSIONS: Our review findings provide strong evidence that treatment with
      hormone therapy in post-menopausal women overall, for either primary or secondary
      prevention of cardiovascular disease events has little if any benefit and causes
      an increase in the risk of stroke and venous thromboembolic events.

PMID- 25754618
TI  - Ultra-broadband terahertz absorption by exciting the orthogonal diffraction in
      dumbbell-shaped gratings.
AB  - Metamaterials, artificial electromagnetic media consisting of periodical
      subwavelength metal-based micro-structures, were widely suggested for the
      absorption of terahertz (THz) waves. However, they have been suffered from the
      absorption of THz waves just in the single-frequency owing to its resonance
      features. Here, in this paper, we propose a simple periodical structure, composed
      of two 90 degree crossed dumbbell-shaped doped-silicon grating arrays, to
      demonstrate broadband THz wave absorption. Our theoretical and experimental
      results illustrate that THz waves can be efficiently absorbed more than 95%
      ranging from 0.92 THz to 2.4 THz. Such an ultra-wideband polarization-independent
      THz absorber is realized mainly based on the mechanisms of the anti-reflection
      effect together with the [+/-1, 0]-order and [0, +/-1]-order grating
      diffractions. The application of our investigation can be extend to THz couplers,
      filters, imaging, and so on. 

PMID- 25754619
TI  - Synthesis of onion-peel nanodendritic structures with sequential functional
      phosphorus diversity.
AB  - The preparation of novel families of phosphorus-based macromolecular
      architectures called "onion peel" phosphorus nanodendritic systems is reported.
      This construct is based on the versatility of methods of synthesis using several
      building blocks and on the capability of these systems to undergo regioselective
      reactions within the cascade structure. Sustainable metal-free routes such as the
      Staudinger reaction or Schiff-base condensation, involving only water and
      nitrogen as byproducts, allow access to several dendritic macromolecules bearing
      up to seven different phosphorus units in their backbone, each of them featuring
      specific reactivity. The presence of the highly aurophilic P=N-P=S fragment
      enables selective ligation of Au(I) within the dendritic framework.

PMID- 25754620
TI  - Human capacity for explosive force production: neural and contractile
      determinants.
AB  - This study assessed the integrative neural and contractile determinants of human
      knee extension explosive force production. Forty untrained participants performed
      voluntary and involuntary (supramaximally evoked twitches and octets - eight
      pulses at 300 Hz that elicit the maximum possible rate of force development)
      explosive isometric contractions of the knee extensors. Explosive force (F0-150
      ms) and sequential rate of force development (RFD, 50-ms epochs) were measured.
      Surface electromyography (EMG) amplitude was recorded (superficial quadriceps and
      hamstrings, 50-ms epochs) and normalized (quadriceps to Mmax, hamstrings to
      EMGmax). Maximum voluntary force (MVF) was also assessed. Multiple linear
      regressions assessed the significant neural and contractile determinants of
      absolute and relative (%MVF) explosive force and sequential RFD. Explosive force
      production exhibited substantial interindividual variability, particularly during
      the early phase of contraction [F50, 13-fold (absolute); 7.5-fold (relative)].
      Multiple regression explained 59-93% (absolute) and 35-60% (relative) of the
      variance in explosive force production. The primary determinants of explosive
      force changed during the contraction (F0-50, quadriceps EMG and Twitch F; RFD50
      100, Octet RFD0-50; F100-150, MVF). In conclusion, explosive force production was
      largely explained by predictor neural and contractile variables, but the specific
      determinants changed during the phase of contraction. 

PMID- 25754622
TI  - Mesoporous bismuth ferrite with amplified magnetoelectric coupling and electric
      field-induced ferrimagnetism.
AB  - Coupled ferromagnetic and ferroelectric materials, known as multiferroics, are an
      important class of materials that allow magnetism to be manipulated through the
      application of electric fields. Bismuth ferrite, BiFeO3, is the most-studied
      intrinsic magnetoelectric multiferroic because it maintains both ferroelectric
      and magnetic ordering to well above room temperature. Here we report the use of
      epitaxy-free wet chemical methods to create strained nanoporous BiFeO3. We find
      that the strained material shows large changes in saturation magnetization on
      application of an electric field, changing from 0.04 to 0.84 MUb per Fe. For
      comparison, non-porous films produced using analogous methods change from just
      0.002 to 0.01 MUb per Fe on application of the same electric field. The results
      indicate that nanoscale architecture can complement strain-layer epitaxy as a
      tool to strain engineer magnetoelectric materials. 

PMID- 25754621
TI  - Use of serial multiparametric magnetic resonance imaging in the management of
      patients with prostate cancer on active surveillance.
AB  - INTRODUCTION: We evaluated the performance of multiparametric prostate magnetic
      resonance imaging (mp-MRI) and MRI/transrectal ultrasound (TRUS) fusion-guided
      biopsy (FB) for monitoring patients with prostate cancer on active surveillance
      (AS). MATERIALS AND METHODS: Patients undergoing mp-MRI and FB of target lesions
      identified on mp-MRI between August 2007 and August 2014 were reviewed. Patients
      meeting AS criteria (Clinical stage T1c, Gleason grade <= 6, prostate-specific
      antigen density <= 0.15, tumor involving <= 2 cores, and <= 50% involvement of
      any single core) based on extended sextant 12-core TRUS biopsy (systematic biopsy
      [SB]) were included. They were followed with subsequent 12-core biopsy as well as
      mp-MRI and MRI/TRUS fusion biopsy at follow-up visits until Gleason score
      progression (Gleason >= 7 in either 12-core or MRI/TRUS fusion biopsy). We
      evaluated whether progression seen on mp-MRI (defined as an increase in suspicion
      level, largest lesion diameter, or number of lesions) was predictive of Gleason
      score progression. RESULTS: Of 152 patients meeting AS criteria on initial SB
      (mean age of 61.4 years and mean prostate-specific antigen level of 5.26 ng/ml),
      34 (22.4%) had Gleason score >= 7 on confirmatory SB/FB. Of the 118 remaining
      patients, 58 chose AS and had at least 1 subsequent mp-MRI with SB/FB (median
      follow-up = 16.1 months). Gleason progression was subsequently documented in 17
      (29%) of these men, in all cases to Gleason 3+4. The positive predictive value
      and negative predictive value of mp-MRI for Gleason progression was 53% (95% CI:
      28%-77%) and 80% (95% CI: 65%-91%), respectively. The sensitivity and specificity
      of mp-MRI for increase in Gleason were also 53% and 80%, respectively. The number
      needed to biopsy to detect 1 Gleason progression was 8.74 for SB vs. 2.9 for FB.
      CONCLUSIONS: Stable findings on mp-MRI are associated with Gleason score
      stability. mp-MRI appears promising as a useful aid for reducing the number of
      biopsies in the management of patients on AS. A prospective evaluation of mp-MRI
      as a screen to reduce biopsies in the follow-up of men on AS appears warranted.

PMID- 25754623
TI  - Endogenous metabolites and inflammasome activity in early childhood and links to
      respiratory diseases.

PMID- 25754624
TI  - Knowledge and perceptions of tobacco-related media in rural Appalachia.
AB  - INTRODUCTION: A critical component of the US Food and Drug Administration's new
      authority to regulate tobacco products is understanding communications and
      marketing of tobacco products and their perceived risks in different geographic,
      age, race, ethnic and socioeconomic groups. Such information might be
      particularly useful in subgroups of the population or geographic areas that
      experience high tobacco use and suffer a disproportionate burden from tobacco
      related diseases. For certain populations, there may be additional cultural
      factors unique to the geographical region which may promote smoking behavior. The
      purpose of the present study was to examine the perceptions of tobacco-related
      media messages among a sample of rural Appalachian natives, a population with
      smoking rates higher than the national average and who are disproportionately
      affected by tobacco-related and other cancers. METHODS: A series of four focus
      group sessions were conducted in a north-central area of Pennsylvania, in one of
      52 counties in Pennsylvania designated as within the Appalachian region.
      Participants were recruited via direct mail letters, advertisements in a local
      newspaper, and recruiting flyers posted at the local library. The focus groups
      were moderated by trained professional staff from The Pennsylvania State
      University's Center for Survey Research (CSR). Focus group sessions sought to
      examine perceptions of tobacco-related media in an Appalachian region of
      Pennsylvania. The sessions were audiotaped and transcribed, and the data was
      analyzed using qualitative approaches. RESULTS: Participants reported that pro
      tobacco ads and favorable messages were received through the internet, direct
      mail, convenience stores, billboards, movies, and other sources. Anti-tobacco
      messages were identified primarily from television and magazines. In general,
      participants concluded that quitting was a matter of choice and was not
      influenced by pro- or anti-tobacco media. CONCLUSIONS: These results indicate
      that both pro- and anti-tobacco messages from a variety of sources are highly
      recognized and remembered in detail in Appalachia, but the effectiveness of anti
      tobacco messages is questionable within this group. It was found that, without
      exception, group members reported that no media messages - either pro- or anti
      tobacco - had any meaningful impact on their current behavior. Group members did,
      however, recognize that media messages influenced their behavior at the time they
      were first starting to smoke. The failure of these messages to connect with this
      population may reflect the lack of specific tailoring of messages to fit the
      distinct culture and values of this Appalachian population.

PMID- 25754625
TI  - Detection of biotinidase gene mutations in Turkish patients ascertained by
      newborn and family screening.
AB  - The incidence of biotinidase deficiency in Turkey is currently one of the highest
      in the world. To expand upon the information about the biotinidase gene (BTD)
      variations in Turkish patients, we conducted a mutation screening in a large
      series (n = 210) of probands with biotinidase deficiency, using denaturing high
      performance liquid chromatography and direct DNA sequencing. The putative effects
      of novel mutations were predicted by computational program. Twenty-six mutations,
      including six novels (p.C143F, p.T244I, c.1212-1222del11, c.1320delG, p.V457L,
      p.G480R) were identified. Nine of the patients were symptomatic at the initial
      clinical assessment with presentations of seizures, encephalopathy, and lactic
      acidemia. The most common mutation in this group of symptomatic patients was c.98
      104 del7ins3. Among the screened patients, 72 have partial and 134 have profound
      biotinidase deficiency (BD) of which 106 are homozygous for BTD mutations. The
      common mutations (p.R157H, p.D444H, c.98-104del7ins3, p.T532M) cumulatively
      accounted for 72.3% of all the mutant alleles in the Turkish population.
      CONCLUSION: The identification of common mutations and hot spot regions of the
      BTD gene in Turkish patients is important for mutation screening in the Turkish
      population and helps to ascertain carriers, may have impact on genetic counseling
      and implementing prevention programs.

PMID- 25754626
TI  - Predictive genetic markers of coagulation, inflammation and apoptosis in Perthes
      disease-Serbian experience.
AB  - Perthes disease is one of the most common forms of pediatric femoral head
      osteonecrosis with an unknown etiology. Coagulation factors were the first
      genetic factors suspected to have a role in the pathogenesis of this disease, but
      studies showed inconsistent results. It is described that inflammation is present
      during early stages of Perthes disease, but its genetic aspect has not been
      studied extensively. Little is known regarding the status of apoptotic factors
      during the repair process that leads to the occurrence of hip deformity in
      patients. Therefore, the aim of this study was to analyze major mediators
      involved in coagulation, inflammation, and apoptotic processes as possible
      causative factors of Perthes disease. The study cohort consisted of 37 patients.
      Gene variants of TNF-alpha, FV, FII, and MTHFR genes were determined by PCR-RFLP,
      while IL-3 and PAI-1 were genotyped by direct sequencing. The expression level of
      Bax, Bcl-2, Bcl2L12, Fas and FasL was analyzed by quantitative reverse
      transcriptase polymerase chain reaction (qRT-PCR) technique. Our results showed a
      significantly increased level of expression of pro-apoptotic factor Bax along
      with significantly higher Bax/Bcl-2 ratio in the patient group. CONCLUSION: The
      results presented indicate that apoptosis could be one of the factors
      contributing to the lack of balanced bone remodeling process in Perthes patients.

PMID- 25754627
TI  - Reactivity of pyruvic acid and its derivatives towards reactive oxygen species.
AB  - Pyruvic acid and its derivatives occurring in most biological systems are known
      to exhibit several pharmacological properties, such as anti-inflammatory,
      neuroprotective or anticancer, many of which are suggested to originate from
      their antioxidant and free radical scavenger activity. The therapeutic potential
      of these compounds is a matter of particular interest, due to their mechanisms of
      action, particularly their possible antioxidant behaviour. Here, we report the
      results of a study of the effect of pyruvic acid (PA), ethyl pyruvate (EP) and
      sodium pyruvate (SP) on reactions generating reactive oxygen species (ROS), such
      as superoxide anion radicals, hydroxyl radicals and singlet oxygen, and their
      total antioxidant capacity. Chemiluminescence (CL) and spectrophotometry
      techniques were employed. The pyruvate analogues studied were found to inhibit
      the CL signal arising from superoxide anion radicals in a dose-dependent manner
      with IC50 = 0.0197 +/- 0.002 mM for EP and IC50 = 69.2 +/- 5.2 mM for PA. These
      compounds exhibited a dose-dependent decrease in the CL signal of the luminol +
      H2O2 system over the range 0.5-10 mM with IC50 values of 1.71 +/- 0.12 mM for PA,
      3.85 +/- 0.21 mM for EP and 22.91 +/- 1.21 mM for SP. Furthermore, these
      compounds also inhibited hydroxyl radical-dependent deoxyribose degradation in a
      dose-dependent manner over the range 0.5-200 mM, with IC50 values of 33.2 +/- 0.3
      mM for SP, 116.1 +/- 6.2 mM for EP and 168.2 +/- 6.2 mM for PA. All the examined
      compounds also showed antioxidant capacity when estimated using the ferric
      ferrozine assay. The results suggest that the antioxidant activities of pyruvate
      derivatives may reflect a direct effect on scavenging ROS and, in part, be
      responsible for their pharmacological actions.

PMID- 25754628
TI  - Combination effect of regulatory T-cell depletion and ionizing radiation in mouse
      models of lung and colon cancer.
AB  - PURPOSE: To investigate the potential of low-dose cyclophosphamide (LD-CTX) and
      anti-CD25 antibody to prevent activation of regulatory T cells (Tregs) during
      radiation therapy. METHODS AND MATERIALS: We used LD-CTX and anti-CD25 monoclonal
      antibody as a means to inhibit Tregs and improve the therapeutic effect of
      radiation in a mouse model of lung and colon cancer. Mice were irradiated on the
      tumor mass of the right leg and treated with LD-CTX and anti-CD25 antibody once
      per week for 3 weeks. RESULTS: Combined treatment of LD-CTX or anti-CD25 antibody
      with radiation significantly decreased Tregs in the spleen and tumor compared
      with control and irradiation only in both lung and colon cancer. Combinatorial
      treatments resulted in a significant increase in the effector T cells, longer
      survival rate, and suppressed irradiated and distal nonirradiated tumor growth.
      Specifically, the combinatorial treatment of LD-CTX with radiation resulted in
      outstanding regression of local and distant tumors in colon cancer, and almost
      all mice in this group survived until the end of the study. CONCLUSIONS: Our
      results suggest that Treg depletion strategies may enhance radiation-mediated
      antitumor immunity and further improve outcomes after radiation therapy.

PMID- 25754629
TI  - Stereotactic radiosurgery for melanoma brain metastases in patients receiving
      ipilimumab: safety profile and efficacy of combined treatment.
AB  - PURPOSE: Ipilimumab (Ipi), a monoclonal antibody against cytotoxic T-lymphocyte
      antigen-4, has been shown to improve survival in patients with metastatic
      melanoma. In this single-institution study, we investigated the safety and
      efficacy of stereotactic radiosurgery (SRS) for patients with melanoma brain
      metastases (BMs) who also received Ipi. METHODS AND MATERIALS: From 2005 to 2011,
      46 patients with melanoma received Ipi and underwent single-fraction SRS for BMs.
      A total of 113 BMs (91% intact, 9% postoperative) were treated with a median dose
      of 21 Gy (range, 15-24 Gy). Ipi was given at 3 mg/kg (54%) or 10 mg/kg (46%) for
      a median of 4 doses (range, 1-21). Adverse events were recorded with the use of
      the Common Terminology Criteria for Adverse Events 3.0. Kaplan-Meier methods were
      used to estimate survival, and Cox regression was used to investigate
      associations. RESULTS: Fifteen patients received SRS during Ipi, 19 received SRS
      before Ipi, and 12 received SRS after Ipi. Overall survival (OS) was
      significantly associated with the timing of SRS/Ipi (P=.035) and melanoma
      specific graded prognostic assessment (P=.013). Patients treated with SRS during
      or before Ipi had better OS and less regional recurrence than did those treated
      with SRS after Ipi (1-year OS 65% vs 56% vs 40%, P=.008; 1-year regional
      recurrence 69% vs 64% vs 92%, P=.003). SRS during Ipi also yielded a trend toward
      less local recurrence than did SRS before or after Ipi (1-year local recurrence
      0% vs 13% vs 11%, P=.21). On magnetic resonance imaging, an increase in BM
      diameter to >150% was seen in 50% of patients treated during or before Ipi but in
      only 13% of patients treated after Ipi. Grade 3 to 4 toxicities were seen in 20%
      of patients. CONCLUSION: Overall, the combination of Ipi and SRS appears to be
      well tolerated. Concurrent delivery of Ipi and SRS is associated with favorable
      locoregional control and possibly longer survival. It may also cause a temporary
      increase in tumor size, possibly because of an enhanced immunomodulatory effect.

PMID- 25754630
TI  - Influence of Pulmonary Nodules on Chest Computed Tomography and Risk of
      Recurrence in Stage IV Wilms Tumor.
AB  - PURPOSE: Chest computed tomography (CT) is currently accepted as the main
      modality for initial disease staging and response assessment in Wilms tumor (WT).
      However, there is great variability in the number and size of lung metastases at
      the time of diagnosis and after induction chemotherapy. There is a lack of
      clinical evidence as to how this variability in tumor burden affects choice of
      therapy and disease outcome. This study sought to evaluate a previously proposed
      lung metastases risk stratification system based on CT findings and clinical
      outcomes in stage IV WT patients. METHODS AND MATERIALS: Thirty-five pediatric
      patients with a diagnosis of stage IV WT with evaluable pre- and postdiagnosis CT
      scans between 1997 and 2012 were included in the analysis. Patients were divided
      into low-, intermediate-, and high-risk categories based on the size and number
      of pulmonary metastases before and after 6 weeks of chemotherapy. Association of
      the lung risk groups with lung recurrence-free survival and overall survival at
      each time point was analyzed with relevant covariates. RESULTS: Risk group
      distribution both at diagnosis and after induction chemotherapy was not
      influenced by tumor histology. Initial risk grouping suggested an association
      with disease-free survival at 5 years (P=.074); however, the most significant
      correlation was with postinduction chemotherapy disease status (P=.027). In
      patients with an intermediate or high burden of disease after 6 weeks of
      chemotherapy, despite receiving whole-lung and boost irradiation, survival
      outcomes were poorer. CONCLUSIONS: Pulmonary tumor burden in stage IV WT on chest
      CT can predict disease outcome. Patients with intermediate- or low-risk disease,
      especially after induction therapy, have a higher risk for recurrence. After
      prospective validation, this method may become a valuable tool in adaptation of
      therapy to improve outcome.

PMID- 25754631
TI  - Adjuvant radiation therapy improves local control after surgical resection in
      patients with localized adrenocortical carcinoma.
AB  - PURPOSE: Adrenocortical carcinoma (ACC) is a rare malignancy known for high rates
      of local recurrence, though the benefit of postoperative radiation therapy (RT)
      has not been established. In this study of grossly resected ACC, we compare local
      control of patients treated with surgery followed by adjuvant RT to a matched
      cohort treated with surgery alone. METHODS AND MATERIALS: We retrospectively
      identified patients with localized disease who underwent R0 or R1 resection
      followed by adjuvant RT. Only patients treated with RT at our institution were
      included. Matching to surgical controls was on the basis of stage, surgical
      margin status, tumor grade, and adjuvant mitotane. RESULTS: From 1991 to 2011,
      360 ACC patients were evaluated for ACC at the University of Michigan (Ann Arbor,
      MI). Twenty patients with localized disease received postoperative adjuvant RT.
      These were matched to 20 controls. There were no statistically significant
      differences between the groups with regard to stage, margins, grade, or mitotane.
      Median RT dose was 55 Gy (range, 45-60 Gy). Median follow-up was 34 months. Local
      recurrence occurred in 1 patient treated with RT, compared with 12 patients not
      treated with RT (P=.0005; hazard ratio [HR] 12.59; 95% confidence interval [CI]
      1.62-97.88). However, recurrence-free survival was no different between the
      groups (P=.17; HR 1.52; 95% CI 0.67-3.45). Overall survival was also not
      significantly different (P=.13; HR 1.97; 95% CI 0.57-6.77), with 4 deaths in the
      RT group compared with 9 in the control group. CONCLUSIONS: Postoperative RT
      significantly improved local control compared with the use of surgery alone in
      this case-matched cohort analysis of grossly resected ACC patients. Although this
      retrospective series represents the largest study to date on adjuvant RT for ACC,
      its findings need to be prospectively confirmed.

PMID- 25754632
TI  - Early toxicity in patients treated with postoperative proton therapy for locally
      advanced breast cancer.
AB  - PURPOSE: To report dosimetry and early toxicity data in breast cancer patients
      treated with postoperative proton radiation therapy. METHODS AND MATERIALS: From
      March 2013 to April 2014, 30 patients with nonmetastatic breast cancer and no
      history of prior radiation were treated with proton therapy at a single proton
      center. Patient characteristics and dosimetry were obtained through chart review.
      Patients were seen weekly while on treatment, at 1 month after radiation therapy
      completion, and at 3- to 6-month intervals thereafter. Toxicity was scored using
      Common Terminology Criteria for Adverse Events version 4.0. Frequencies of
      toxicities were tabulated. RESULTS: Median dose delivered was 50.4 Gy (relative
      biological equivalent [RBE]) in 5 weeks. Target volumes included the breast/chest
      wall and regional lymph nodes including the internal mammary lymph nodes (in
      93%). No patients required a treatment break. Among patients with >3 months of
      follow-up (n=28), grade 2 dermatitis occurred in 20 patients (71.4%), with 8
      (28.6%) experiencing moist desquamation. Grade 2 esophagitis occurred in 8
      patients (28.6%). Grade 3 reconstructive complications occurred in 1 patient. The
      median planning target volume V95 was 96.43% (range, 79.39%-99.60%). The median
      mean heart dose was 0.88 Gy (RBE) [range, 0.01-3.20 Gy (RBE)] for all patients,
      and 1.00 Gy (RBE) among patients with left-sided tumors. The median V20 of the
      ipsilateral lung was 16.50% (range, 6.1%-30.3%). The median contralateral lung V5
      was 0.34% (range, 0%-5.30%). The median maximal point dose to the esophagus was
      45.65 Gy (RBE) [range, 0-65.4 Gy (RBE)]. The median contralateral breast mean
      dose was 0.29 Gy (RBE) [range, 0.03-3.50 Gy (RBE)]. CONCLUSIONS: Postoperative
      proton therapy is well tolerated, with acceptable rates of skin toxicity. Proton
      therapy favorably spares normal tissue without compromising target coverage.
      Further follow-up is necessary to assess for clinical outcomes and
      cardiopulmonary toxicities.

PMID- 25754633
TI  - Benefit of consolidative radiation therapy for primary bone diffuse large B-cell
      lymphoma.
AB  - PURPOSE: Outcomes for patients with diffuse large B-cell lymphoma (DLBCL) differ
      according to the site of presentation. With effective chemotherapy, the need for
      consolidative radiation therapy (RT) is controversial. We investigated the
      influence of primary bone presentation and receipt of consolidative RT on
      progression-free survival (PFS) and overall survival (OS) in patients with DLBCL.
      METHODS AND MATERIALS: We identified 102 patients with primary bone DLBCL treated
      consecutively from 1988 through 2013 and extracted clinical, pathologic, and
      treatment characteristics from the medical records. Survival outcomes were
      calculated by the Kaplan-Meier method, with factors affecting survival determined
      by log-rank tests. Univariate and multivariate analyses were done with a Cox
      regression model. RESULTS: The median age was 55 years (range, 16-87 years). The
      most common site of presentation was in the long bones. Sixty-five patients (63%)
      received R-CHOP-based chemotherapy, and 74 (72%) received rituximab. RT was given
      to 67 patients (66%), 47 with stage I to II and 20 with stage III to IV disease.
      The median RT dose was 44 Gy (range, 24.5-50 Gy). At a median follow-up time of
      82 months, the 5-year PFS and OS rates were 80% and 82%, respectively. Receipt of
      RT was associated with improved 5-year PFS (88% RT vs 63% no RT, P=.0069) and OS
      (91% vs 68%, P=.0064). On multivariate analysis, the addition of RT significantly
      improved PFS (hazard ratio [HR] = 0.14, P=.014) with a trend toward an OS benefit
      (HR=0.30, P=.053). No significant difference in PFS or OS was found between
      patients treated with 30 to 35 Gy versus >= 36 Gy (P=.71 PFS and P=.31 OS).
      CONCLUSION: Patients with primary bone lymphoma treated with standard
      chemotherapy followed by RT can have excellent outcomes. The use of consolidative
      RT was associated with significant benefits in both PFS and OS.

PMID- 25754634
TI  - Minimizing late effects for patients with mediastinal Hodgkin lymphoma: deep
      inspiration breath-hold, IMRT, or both?
AB  - PURPOSE: Hodgkin lymphoma (HL) survivors have an increased risk of cardiovascular
      disease (CD), lung cancer, and breast cancer. We investigated the risk for the
      development of CD and secondary lung, breast, and thyroid cancer after radiation
      therapy (RT) delivered with deep inspiration breath-hold (DIBH) compared with
      free-breathing (FB) using 3-dimensional conformal RT (3DCRT) and intensity
      modulated RT (IMRT). The aim of this study was to determine which treatment
      modality best reduced the combined risk of life-threatening late effects in
      patients with mediastinal HL. METHODS AND MATERIALS: Twenty-two patients with
      early-stage mediastinal HL were eligible for the study. Treatment plans were
      calculated with both 3DCRT and IMRT on both DIBH and FB planning computed
      tomographic scans. We reported the estimated dose to the heart, lung, female
      breasts, and thyroid and calculated the estimated life years lost attributable to
      CD and to lung, breast, and thyroid cancer. RESULTS: DIBH lowered the estimated
      dose to heart and lung regardless of delivery technique (P<.001). There was no
      significant difference between IMRT-FB and 3DCRT-DIBH in mean heart dose, heart
      V20Gy, and lung V20Gy. The mean breast dose was increased with IMRT regardless of
      breathing technique. Life years lost was lowest with DIBH and highest with FB.
      CONCLUSIONS: In this cohort, 3DCRT-DIBH resulted in lower estimated doses and
      lower lifetime excess risks than did IMRT-FB. Combining IMRT and DIBH could be
      beneficial for a subgroup of patients.

PMID- 25754635
TI  - Brain regeneration in Drosophila involves comparison of neuronal fitness.
AB  - Darwinian-like cell selection has been studied during development and cancer [1
      11]. Cell selection is often mediated by direct intercellular comparison of cell
      fitness, using "fitness fingerprints" [12-14]. In Drosophila, cells compare their
      fitness via several isoforms of the transmembrane protein Flower [12, 13]. Here,
      we studied the role of intercellular fitness comparisons during regeneration.
      Regeneration-competent organisms are traditionally injured by amputation [15,
      16], whereas in clinically relevant injuries such as local ischemia or traumatic
      injury, damaged tissue remains within the organ [17-19]. We reasoned that
      "Darwinian" interactions between old and newly formed tissues may be important in
      the elimination of damaged cells. We used a model of adult brain regeneration in
      Drosophila in which mechanical puncture activates regenerative neurogenesis based
      on damage-responsive stem cells [20]. We found that apoptosis after brain injury
      occurs in damage-exposed tissue located adjacent to zones of de novo
      neurogenesis. Injury-affected neurons start to express isoforms of the Flower
      cell fitness indicator protein not found on intact neurons. We show that this
      change in the neuronal fitness fingerprint is required to recognize and eliminate
      such neurons. Moreover, apoptosis is inhibited if all neurons express "low
      fitness" markers, showing that the availability of new and healthy cells drives
      tissue replacement. In summary, we found that elimination of impaired tissue
      during brain regeneration requires comparison of neuronal fitness and that tissue
      replacement after brain damage is coordinated by injury-modulated fitness
      fingerprints. Intercellular fitness comparisons between old and newly formed
      tissues could be a general mechanism of regenerative tissue replacement.

PMID- 25754636
TI  - Ecological knowledge, leadership, and the evolution of menopause in killer
      whales.
AB  - Classic life-history theory predicts that menopause should not occur because
      there should be no selection for survival after the cessation of reproduction
      [1]. Yet, human females routinely live 30 years after they have stopped
      reproducing [2]. Only two other species-killer whales (Orcinus orca) and short
      finned pilot whales (Globicephala macrorhynchus) [3, 4]-have comparable
      postreproductive lifespans. In theory, menopause can evolve via inclusive fitness
      benefits [5, 6], but the mechanisms by which postreproductive females help their
      kin remain enigmatic. One hypothesis is that postreproductive females act as
      repositories of ecological knowledge and thereby buffer kin against environmental
      hardships [7, 8]. We provide the first test of this hypothesis using a unique
      long-term dataset on wild resident killer whales. We show three key results.
      First, postreproductively aged females lead groups during collective movement in
      salmon foraging grounds. Second, leadership by postreproductively aged females is
      especially prominent in difficult years when salmon abundance is low. This
      finding is critical because salmon abundance drives both mortality and
      reproductive success in resident killer whales [9, 10]. Third, females are more
      likely to lead their sons than they are to lead their daughters, supporting
      predictions of recent models [5] of the evolution of menopause based on kinship
      dynamics. Our results show that postreproductive females may boost the fitness of
      kin through the transfer of ecological knowledge. The value gained from the
      wisdom of elders can help explain why female resident killer whales and humans
      continue to live long after they have stopped reproducing. 

PMID- 25754637
TI  - Cyclin B3 is a mitotic cyclin that promotes the metaphase-anaphase transition.
AB  - The timing mechanism for mitotic progression is still poorly understood. The
      spindle assembly checkpoint (SAC), whose reversal upon chromosome alignment is
      thought to time anaphase [1-3], is functional during the rapid mitotic cycles of
      the Drosophila embryo; but its genetic inactivation had no consequence on the
      timing of the early mitoses. Mitotic cyclins-Cyclin A, Cyclin B, and Cyclin B3
      influence mitotic progression and are degraded in a stereotyped sequence [4-11].
      RNAi knockdown of Cyclins A and B resulted in a Cyclin B3-only mitosis in which
      anaphase initiated prior to chromosome alignment. Furthermore, in such a Cyclin
      B3-only mitosis, colchicine-induced SAC activation failed to block Cyclin B3
      destruction, chromosome decondensation, or nuclear membrane re-assembly.
      Injection of Cyclin B proteins restored the ability of SAC to prevent Cyclin B3
      destruction. Thus, SAC function depends on particular cyclin types. Changing
      Cyclin B3 levels showed that it accelerated progress to anaphase, even in the
      absence of SAC function. The impact of Cyclin B3 on anaphase initiation appeared
      to decline with developmental progress. Our results show that different cyclin
      types affect anaphase timing differently in the early embryonic divisions. The
      early-destroyed cyclins-Cyclins A and B-restrain anaphase-promoting
      complex/cyclosome (APC/C) function, whereas the late-destroyed cyclin, Cyclin B3,
      stimulates function. We propose that the destruction schedule of cyclin types
      guides mitotic exit by affecting both Cdk1 and APC/C, whose activities change as
      each cyclin type is lost. 

PMID- 25754638
TI  - Visuomotor transformations underlying hunting behavior in zebrafish.
AB  - Visuomotor circuits filter visual information and determine whether or not to
      engage downstream motor modules to produce behavioral outputs. However, the
      circuit mechanisms that mediate and link perception of salient stimuli to
      execution of an adaptive response are poorly understood. We combined a virtual
      hunting assay for tethered larval zebrafish with two-photon functional calcium
      imaging to simultaneously monitor neuronal activity in the optic tectum during
      naturalistic behavior. Hunting responses showed mixed selectivity for
      combinations of visual features, specifically stimulus size, speed, and contrast
      polarity. We identified a subset of tectal neurons with similar highly selective
      tuning, which show non-linear mixed selectivity for visual features and are
      likely to mediate the perceptual recognition of prey. By comparing neural
      dynamics in the optic tectum during response versus non-response trials, we
      discovered premotor population activity that specifically preceded initiation of
      hunting behavior and exhibited anatomical localization that correlated with motor
      variables. In summary, the optic tectum contains non-linear mixed selectivity
      neurons that are likely to mediate reliable detection of ethologically relevant
      sensory stimuli. Recruitment of small tectal assemblies appears to link
      perception to action by providing the premotor commands that release hunting
      responses. These findings allow us to propose a model circuit for the visuomotor
      transformations underlying a natural behavior. 

PMID- 25754639
TI  - Wash interacts with lamin and affects global nuclear organization.
AB  - The cytoplasmic functions of Wiskott-Aldrich syndrome family (WAS) proteins are
      well established and include roles in cytoskeleton reorganization and membrane
      cytoskeletal interactions important for membrane/vesicle trafficking,
      morphogenesis, immune response, and signal transduction. Misregulation of these
      proteins is associated with immune deficiency and metastasis [1-4]. Cytoplasmic
      WAS proteins act as effectors of Rho family GTPases and polymerize branched actin
      through the Arp2/3 complex [1, 5]. Previously, we identified Drosophila washout
      (wash) as a new member of the WAS family with essential cytoplasmic roles in
      early development [6, 7]. Studies in mammalian cells and Dictyostelium suggest
      that WASH functions primarily in a multiprotein complex that regulates endosome
      shape and trafficking in an Arp2/3-dependent manner [8-11]. However, roles for
      classically cytoplasmic proteins in the nucleus are beginning to emerge, in
      particular, as participants in the regulation of gene expression [12, 13]. Here,
      we show that Drosophila Wash is present in the nucleus, where it plays a key role
      in global nuclear organization. wash mutant and knockdown nuclei disrupt
      subnuclear structures/organelles and exhibit the abnormal wrinkled morphology
      reminiscent of those observed in diverse laminopathies [14-16]. We find that
      nuclear Wash interacts with B-type Lamin (Lamin Dm0), and, like Lamin, Wash
      associates with constitutive heterochromatin. Wash knockdown increases chromatin
      accessibility of repressive compartments and results in a global redistribution
      of repressive histone modifications. Thus, our results reveal a novel role for
      Wash in modulating nucleus morphology and in the organization of both chromatin
      and non-chromatin nuclear sub-structures. 

PMID- 25754640
TI  - Myosin 18A coassembles with nonmuscle myosin 2 to form mixed bipolar filaments.
AB  - Class-18 myosins are most closely related to conventional class-2 nonmuscle
      myosins (NM2). Surprisingly, the purified head domains of Drosophila, mouse, and
      human myosin 18A (M18A) lack actin-activated ATPase activity and the ability to
      translocate actin filaments, suggesting that the functions of M18A in vivo do not
      depend on intrinsic motor activity. M18A has the longest coiled coil of any
      myosin outside of the class-2 myosins, suggesting that it might form bipolar
      filaments similar to conventional myosins. To address this possibility, we
      expressed and purified full-length mouse M18A using the baculovirus/Sf9 system.
      M18A did not form large bipolar filaments under any of the conditions tested.
      Instead, M18A formed an ~ 65-nm-long bipolar structure with two heads at each
      end. Importantly, when NM2 was polymerized in the presence of M18A, the two
      myosins formed mixed bipolar filaments, as evidenced by cosedimentation, electron
      microscopy, and single-molecule imaging. Moreover, super-resolution imaging of
      NM2 and M18A using fluorescently tagged proteins and immunostaining of endogenous
      proteins showed that NM2 and M18A are present together within individual
      filaments inside living cells. Together, our in vitro and live-cell imaging data
      argue strongly that M18A coassembles with NM2 into mixed bipolar filaments. M18A
      could regulate the biophysical properties of these filaments and, by virtue of
      its extra N- and C-terminal domains, determine the localization and/or molecular
      interactions of the filaments. Given the numerous, fundamental cellular and
      developmental roles attributed to NM2, our results have far-reaching biological
      implications.

PMID- 25754641
TI  - Sleep interacts with abeta to modulate intrinsic neuronal excitability.
AB  - BACKGROUND: Emerging data suggest an important relationship between sleep and
      Alzheimer's disease (AD), but how poor sleep promotes the development of AD
      remains unclear. RESULTS: Here, using a Drosophila model of AD, we provide
      evidence suggesting that changes in neuronal excitability underlie the effects of
      sleep loss on AD pathogenesis. beta-amyloid (Abeta) accumulation leads to reduced
      and fragmented sleep, while chronic sleep deprivation increases Abeta burden.
      Moreover, enhancing sleep reduces Abeta deposition. Increasing neuronal
      excitability phenocopies the effects of reducing sleep on Abeta, and decreasing
      neuronal activity blocks the elevated Abeta accumulation induced by sleep
      deprivation. At the single neuron level, we find that chronic sleep deprivation,
      as well as Abeta expression, enhances intrinsic neuronal excitability.
      Importantly, these data reveal that sleep loss exacerbates Abeta-induced
      hyperexcitability and suggest that defects in specific K(+) currents underlie the
      hyperexcitability caused by sleep loss and Abeta expression. Finally, we show
      that feeding levetiracetam, an anti-epileptic medication, to Abeta-expressing
      flies suppresses neuronal excitability and significantly prolongs their lifespan.
      CONCLUSIONS: Our findings directly link sleep loss to changes in neuronal
      excitability and Abeta accumulation and further suggest that neuronal
      hyperexcitability is an important mediator of Abeta toxicity. Taken together,
      these data provide a mechanistic framework for a positive feedback loop, whereby
      sleep loss and neuronal excitation accelerate the accumulation of Abeta, a key
      pathogenic step in the development of AD.

PMID- 25754642
TI  - Ocular dominance plasticity disrupts binocular inhibition-excitation matching in
      visual cortex.
AB  - BACKGROUND: To ensure that neuronal networks function in a stable fashion,
      neurons receive balanced inhibitory and excitatory inputs. In various brain
      regions, this balance has been found to change temporarily during plasticity.
      Whether changes in inhibition have an instructive or permissive role in
      plasticity remains unclear. Several studies have addressed this question using
      ocular dominance plasticity in the visual cortex as a model, but so far, it
      remains controversial whether changes in inhibition drive this form of plasticity
      by directly affecting eye-specific responses or through increasing the plasticity
      potential of excitatory connections. RESULTS: We tested how three major classes
      of interneurons affect eye-specific responses in normally reared or monocularly
      deprived mice by optogenetically suppressing their activity. We find that in
      contrast to somatostatin-expressing or vasoactive intestinal polypeptide
      expressing interneurons, parvalbumin (PV)-expressing interneurons strongly
      inhibit visual responses. In individual neurons of normal mice, inhibition and
      excitation driven by either eye are balanced, and suppressing PV interneurons
      does not alter ocular preference. Monocular deprivation disrupts the binocular
      balance of inhibition and excitation in individual neurons, causing suppression
      of PV interneurons to change their ocular preference. Importantly, however, these
      changes do not consistently favor responses to one of the eyes at the population
      level. CONCLUSIONS: Monocular deprivation disrupts the binocular balance of
      inhibition and excitation of individual cells. This disbalance does not affect
      the overall expression of ocular dominance. Our data therefore support a
      permissive rather than an instructive role of inhibition in ocular dominance
      plasticity.

PMID- 25754643
TI  - Mantises exchange angular momentum between three rotating body parts to jump
      precisely to targets.
AB  - Flightless animals have evolved diverse mechanisms to control their movements in
      air, whether falling with gravity or propelling against it. Many insects jump as
      a primary mode of locomotion and must therefore precisely control the large
      torques generated during takeoff. For example, to minimize spin (angular momentum
      of the body) at takeoff, plant-sucking bugs apply large equal and opposite
      torques from two propulsive legs [1]. Interacting gear wheels have evolved in
      some to give precise synchronization of these legs [2, 3]. Once airborne, as a
      result of either jumping or falling, further adjustments may be needed to control
      trajectory and orient the body for landing. Tails are used by geckos to control
      pitch [4, 5] and by Anolis lizards to alter direction [6, 7]. When falling, cats
      rotate their body [8], while aphids [9] and ants [10, 11] manipulate wind
      resistance against their legs and thorax. Falling is always downward, but
      targeted jumping must achieve many possible desired trajectories. We show that
      when making targeted jumps, juvenile wingless mantises first rotated their
      abdomen about the thorax to adjust the center of mass and thus regulate spin at
      takeoff. Once airborne, they then smoothly and sequentially transferred angular
      momentum in four stages between the jointed abdomen, the two raptorial front
      legs, and the two propulsive hind legs to produce a controlled jump with a
      precise landing. Experimentally impairing abdominal movements reduced the overall
      rotation so that the mantis either failed to grasp the target or crashed into it
      head first. 

PMID- 25754644
TI  - Light evokes rapid circadian network oscillator desynchrony followed by gradual
      phase retuning of synchrony.
AB  - Circadian neural circuits generate near 24-hr physiological rhythms that can be
      entrained by light to coordinate animal physiology with daily solar cycles. To
      examine how a circadian circuit reorganizes its activity in response to light, we
      imaged period (per) clock gene cycling for up to 6 days at single-neuron
      resolution in whole-brain explant cultures prepared from per-luciferase
      transgenic flies. We compared cultures subjected to a phase-advancing light pulse
      (LP) to cultures maintained in darkness (DD). In DD, individual neuronal
      oscillators in all circadian subgroups are initially well synchronized but then
      show monotonic decrease in oscillator rhythm amplitude and synchrony with time.
      The small ventral lateral neurons (s-LNvs) and dorsal lateral neurons (LNds)
      exhibit this decrease at a slower relative rate. In contrast, the LP evokes a
      rapid loss of oscillator synchrony between and within most circadian neuronal
      subgroups, followed by gradual phase retuning of whole-circuit oscillator
      synchrony. The LNds maintain high rhythmic amplitude and synchrony following the
      LP along with the most rapid coherent phase advance. Immunocytochemical analysis
      of PER shows that these dynamics in DD and LP are recapitulated in vivo.
      Anatomically distinct circadian neuronal subgroups vary in their response to the
      LP, showing differences in the degree and kinetics of their loss, recovery and/or
      strengthening of synchrony, and rhythmicity. Transient desynchrony appears to be
      an integral feature of light response of the Drosophila multicellular circadian
      clock. Individual oscillators in different neuronal subgroups of the circadian
      circuit show distinct kinetic signatures of light response and phase retuning.

PMID- 25754645
TI  - Reducing the global environmental impacts of rapid infrastructure expansion.
AB  - Infrastructures, such as roads, mines, and hydroelectric dams, are proliferating
      explosively. Often, this has serious direct and indirect environmental impacts.
      We highlight nine issues that should be considered by project proponents to
      better evaluate and limit the environmental risks of such developments. 

PMID- 25754646
TI  - Alternative mechanisms for talin to mediate integrin function.
AB  - Cell-matrix adhesion is essential for building animals, promoting tissue
      cohesion, and enabling cells to migrate and resist mechanical force. Talin is an
      intracellular protein that is critical for linking integrin extracellular-matrix
      receptors to the actin cytoskeleton. A key question raised by structure-function
      studies is whether talin, which is critical for all integrin-mediated adhesion,
      acts in the same way in every context. We show that distinct combinations of
      talin domains are required for each of three different integrin functions during
      Drosophila development. The partial function of some mutant talins requires
      vinculin, indicating that recruitment of vinculin allows talin to duplicate its
      own activities. The different requirements are best explained by alternative
      mechanisms of talin function, with talin using one or both of its integrin
      binding sites. We confirmed these alternatives by showing that the proximity
      between the second integrin-binding site and integrins differs, suggesting that
      talin adopts different orientations relative to integrins. Finally, we show that
      vinculin and actomyosin activity help change talin's orientation. These findings
      demonstrate that the mechanism of talin function differs in each developmental
      context examined. The different arrangements of the talin molecule relative to
      integrins suggest that talin is able to sense different force vectors, either
      parallel or perpendicular to the membrane. This provides a paradigm for proteins
      whose apparent uniform function is in fact achieved by a variety of distinct
      mechanisms involving different molecular architectures.

PMID- 25754647
TI  - Pagetoid reticulosis tumor cells with double expression of TCRgammadelta and
      TCRalphabeta: an off-target phenomenon or genuine expression?
AB  - Pagetoid reticulosis (PR) is a low-grade primary cutaneous T-cell lymphoma
      showing localized patches or plaques with an intrapeidermal proliferation of
      neoplastic T-cells with heterogeneous immunophenotype. We describe a 73-year-old
      woman with a 8-year history of gluteal lesions of PR, whom large blast cells were
      CD4/CD8 double negative T-cells with an activated cytotoxic profile. The case was
      investigated using a broad panel of monoclonal antibodies including TCRgammaM1, a
      new available antibody that recognizes the gamma chain subunit of the T-cell
      receptor (TCR) in formalin-fixed paraffin-embedded tissue. Large blast cells were
      simultaneously positive for TCRalphabeta and TCRgammadelta with an activated
      cytotoxic phenotype. It is worldwide accepted the mutual exclusive expression of
      TCRalphabeta and TCRgammadelta but six different studies, dealing with
      TCRgammadelta expression in various types of extra-nodal lymphomas, reported
      cases whom tumor cells expressed simultaneously TCRalphabeta and TCRgammadelta.
      Our data and those of similar reports, suggest the possibility of existence of a
      subset of extra-nodal T-cell lymphomas showing simultaneous expression by tumor
      cells of TCRgammadelta and TCRalphabeta with an immunoprofile consistent with an
      origin from TCRgammadelta+ T lymphocytes. This unusual subset has preferential,
      but not exclusive, skin localization and variable epidermotropism. 

PMID- 25754648
TI  - Considerations for Altering Preparation Designs of Porcelain Inlay/Onlay
      Restorations for Nonvital Teeth.
AB  - PURPOSE: The aim of this study was to compare all ceramic inlay/onlay survival
      rates in vital and nonvital teeth having the same cavity design. Filling the pulp
      chamber with ceramic materials or not was also discussed. MATERIALS AND METHODS:
      Ceramic class II inlays/onlays were made on 11 premolars and 30 molars: 14 vital,
      27 endodontically treated. The same tooth preparation design was performed on
      vital and nonvital teeth: In nonvital teeth the pulp chambers were covered by a
      glass ionomer cement until the pulpal floor depths were between 2 and 2.5 mm,
      more likely similar to the vital teeth preparations. In vital teeth, glass
      ionomer was used as a liner to achieve pulpal floor depths between 2 and 2.5 mm
      when needed. The restorations were assessed (at baseline, 6 months, 1 and 2
      years) according to three criteria: marginal discoloration, marginal integrity,
      and fracture of teeth/restorations, consistent with United States Public Health
      Service (USPHS) criteria. RESULTS: Eight teeth (19%) showed minor marginal
      discolorations, while three molars (7%) had loss of marginal integrity. These
      margins were adjusted using rubber polishing cups and were then judged clinically
      acceptable. From these three molars, one was vital and two were endodontically
      treated. No fracture of teeth or restorations was observed. Chi square and exact
      probability tests were used. There was no statistical difference between vital
      and nonvital teeth (p = 0.719 chi-squared and Fisher) or between premolars and
      molars (p = 0.564 chi-squared; 1.000, Fisher). CONCLUSION: Within the limitations
      of this study there was no difference for the same inlay/onlay cavity design
      between vital and nonvital teeth. In nonvital teeth, it seems that filling the
      pulp chamber with a ceramic core material is not important. Long-term observation
      periods are needed to reinforce the clinical behavior outcome.

PMID- 25754649
TI  - Central venous blood gas and acid-base status in conscious dogs and cats.
AB  - To determine the reference level of central venous oxygen saturation (ScvO2) and
      clinical efficacy of central venous blood gas analysis, partial pressures of
      oxygen and carbon dioxide, pH, oxygen saturation, base excess (B.E.) and HCO3
      concentration were compared between simultaneously obtained central venous and
      arterial blood samples from conscious healthy 6 dogs and 5 cats. Comparisons
      between arteriovenous samples were performed by a paired t-test and Bland-Altman
      analysis. Between arteriovenous samples, B.E. showed good agreement, but there
      were significant differences in other parameters in the dogs, and no good
      agreement was detected in cats. The ScvO2 in dogs and cats were 82.3 +/- 3.5 and
      62.4 +/- 13.5%, respectively. Central venous blood gas analysis is indispensable,
      especially in cats. 

PMID- 25754650
TI  - Genetic analysis of low survival rate of pups in RR/Sgn inbred mice.
AB  - Newborn offspring of the inbred mouse RR/Sgn strain have a low survival rate
      prior to weaning. We hypothesized that this is a consequence of an inferior
      nurturing ability of RR/Sgn mothers and that RR/Sgn mothers have a tendency to
      lose their pups. We performed quantitative trait locus (QTL) mapping for inferior
      nurturing ability and tendency to lose pups in RR/Sgn mothers. The number of pups
      was adjusted to 6 per dam on the day of delivery, and the number of surviving
      pups and their total weight (litter weight) were scored at 12 days after birth.
      Nurturing ability was evaluated by litter weight, and tendency to lose pups was
      evaluated by scoring whether or not the mothers lost their pups. For litter
      weight, we identified one significant QTL on chromosome 4 and three suggestive
      QTLs on chromosomes 7, 9 and 17. The RR/Sgn allele was associated with lower
      litter weight at all loci. For the tendency to lose pups, we identified three
      suggestive QTLs on chromosomes 4, 9 and 16. The RR/Sgn allele was associated with
      an increased tendency to lose pups at all loci. These results supported our
      hypothesis that the low survival rate phenotype was attributable, at least in
      part, to a phenotype whereby mothers display inferior nurturing ability and a
      tendency to lose pups. Thus, it suggests that these two traits share genetic
      basis. 

PMID- 25754651
TI  - Effect of methotrexate on cerebellar development in infant rats.
AB  - Six-day-old rats were treated intraperitoneal injections with methotrexate 1
      mg/kg, and the cerebellum was examined. Both the length and width of the vermis
      decreased in the methotrexate-treated group instead of the control from 4 day
      after treatment (DAT) onward. A significant reduction in the width of the
      external granular layer was detected on 2 and 3 DAT in the methotrexate group. By
      4 DAT, the width of the external granular layer of the methotrexate group was
      indistinguishable from the control, and by 8 DAT, it was greater than that of the
      control. The molecular layer of methotrexate group on 8 and 15 DAT was thinner
      than that of the control. On 1 DAT, in the methotrexate group, there were many
      TUNEL and cleaved caspase-3-positive granular cells throughout the external
      granular layer, and they decreased time-dependently. On 1 DAT, in the
      methotrexate group, phospho-histone H3-positive cells in the external granular
      layer were fewer than in the control and tended to increase on 2-4 DAT. The p21
      positive-rate of the external granule cells in the MTX group was higher than in
      the control on 1-4 DAT. These results suggested that methotrexate exposure on
      postnatal day 6 induces a delay, slowing in the migration of external granular
      cells to the inner granular layer, attributed to decrease or inhibition in the
      production of external granular cells that had arisen from apoptosis and the
      decrease in cell proliferative activity, resulting in cerebellar hypoplasia. 

PMID- 25754652
TI  - The role of neighboring infected cattle in bovine leukemia virus transmission
      risk.
AB  - A cohort study was conducted to evaluate the risk of bovine leukemia virus (BLV)
      transmission to uninfected cattle by adjacent infected cattle in 6 dairy farms.
      Animals were initially tested in 2010-2011 using a commercial ELISA kit.
      Uninfected cattle were repeatedly tested every 4 to 6 months until fall of 2012.
      The Cox proportional hazard model with frailty showed that uninfected cattle
      neighboring to infected cattle (n=53) had a significant higher risk of
      seroconversion than those without any infected neighbors (n=81) (hazard ratio:
      12.4, P=0.001), implying that neighboring infected cattle were a significant risk
      factor for BLV transmission. This finding provides scientific support for animal
      health authorities and farmers to segregate infected cattle on farms to prevent
      spread of BLV. 

PMID- 25754657
TI  - Vascular protection with dipeptidyl peptidase-IV inhibitors in diabetes:
      experimental and clinical therapeutics.
AB  - The dipeptidyl peptidase-IV (DPP-IV) inhibitors, also known as gliptins, are
      widely used in clinical practice either as monotherapy or in combination with
      other agents for the management of type 2 diabetes mellitus (T2DM). The gliptins
      are effective, safe, well tolerated, and conveniently administered once/day.
      Moreover, these agents have a low risk for drug interactions and do not require
      initial dosage titrations to lessen adverse effects. They are not only clinically
      desirable, having the most favorable side-effect profile of all available
      antihyperglycemic medications, but they can also be used in any stage of renal or
      hepatic impairment. The antihyperglycemic effects of gliptins are attributed to
      inhibition of the DPP-IV enzyme, thereby prolonging the half-life (t1/2 ) of
      incretin hormones (substrates) to promote glucose-stimulated insulin secretion.
      Beyond their glucose-lowering effects, gliptins may also reduce the risk of
      cardiovascular disease by improving endothelial function, lowering blood
      pressure, reducing inflammation, and delaying the progression of atherosclerosis.
      Although the vascular protective effects of gliptins depend on incretins, the
      contributions of other biologically important endogenous vasoactive substrates of
      DPP-IV are worthy of consideration from a therapeutic standpoint. Future and
      ongoing studies should help determine whether these vascular protective effects
      contribute to improved cardiovascular outcomes in patients with T2DM. The
      experimental and clinical evidence supporting the vascular protective effects of
      gliptins is reviewed. 

PMID- 25754658
TI  - The role of positron emission tomography with 18F-fluorodeoxyglucose integrated
      with computed tomography in the evaluation of patients with multiple myeloma
      undergoing allogeneic stem cell transplantation.
AB  - Positron emission tomography (PET) integrated with computed tomography (PET/CT)
      has been reported to be useful for screening myelomatous lesions at diagnosis in
      patients with multiple myeloma (MM) and for monitoring response to autologous
      stem cell transplantation (auto-SCT). The aim of the study was to evaluate the
      prognostic significance of PET/CT in MM patients who received allogeneic stem
      cell transplantation (allo-SCT). Patients who underwent upfront auto-SCT followed
      by allo-SCT, either as consolidation or salvage treatment, were studied with
      PET/CT before and/or within 6 months after allo-SCT. The number, the maximum
      standard uptake value (SUV), and the location (medullary or extramedullary) of
      focal lesions (FLs) were recorded and investigated as predictors of progression
      free survival (PFS) and overall survival (OS) by univariate and multivariate
      analyses. Fifty-four patients had a PET/CT scan before allo-SCT. Of these, 22
      patients (41%) had a negative PET/CT scan, 11 patients (20%) showed 1 to 3 FLs,
      and 21 patients (39%) had either a diffuse bone marrow involvement or more than 3
      FLs. SUV was >4.2 in 21 patients (39%) and extramedullary disease (EMD) was
      present in 6 patients (11%). Multivariate analysis of prognostic factors before
      allo-SCT showed that persistence of EMD at transplantation was an independent
      predictor of poor PFS, whereas OS was negatively influenced by unrelated donor
      and SUV > 4.2. Fifty-nine patients had a PET/CT scan within 6 months after allo
      SCT. Multivariate analysis of post-treatment variables showed that persistence of
      EMD and failure to obtain complete response or very good partial response after
      allo-SCT were strongly associated with shorter PFS and OS. Of the 46 patients
      with evaluable PET/CT scans both before and 6 months after allo-SCT, the 23
      patients who maintained or reached a PET complete remission showed a
      significantly prolonged PFS and OS compared with the 23 patients with persistence
      of any PET positivity (2-year PFS: 51% versus 25%, P = .03; 2-year OS: 81% versus
      47%, P = .001). This study indicates that PET/CT imaging before and after allo
      SCT is significantly associated with the outcome, suggesting the utility of this
      technique for MM staging before allo-SCT and for response monitoring after the
      transplantation. 

PMID- 25754659
TI  - Two novel alleles, HLA-A*02:07:06 and HLA-A*02:426, were identified in Chinese
      individuals.
AB  - HLA-A*02:07:06 shows 285 A>C and HLA-A*02:426 has 763 G>A change compared with
      HLA-A*02:07:01. 

PMID- 25754660
TI  - Repair of type A dissection with mitral regurgitation using total arch
      replacement with mitral valve surgery.
AB  - BACKGROUND: Mitral regurgitation (MR) is very rare in patients with type A
      dissection. We retrospectively reviewed our experience of total arch replacement
      (TAR) with mitral valve surgery for type A dissection with MR. METHODS: From
      November 2009 to October 2012, 14 patients with type A dissection (chronic = 11;
      acute = 3) with MR underwent TAR combined with mitral valve surgery under
      hypothermic cardiopulmonary bypass with selective cerebral perfusion. The Bentall
      procedure was performed in 11 patients, aortic valve replacement (AVR) in one
      patient, coronary artery bypass grafting (CABG) in three patients, and tricuspid
      valvuloplasty (TVP) in one patient. RESULTS: Thirty-day mortality was 7.1%
      (1/14). One patient died after transfer to another hospital secondary to renal
      failure. Low cardiac output syndrome was observed in three patients (21.4%,
      3/14), one of whom underwent left ventricular assist device implantation.
      Continuous renal replacement therapy was performed in four cases (28.6%, 4/14).
      Two patients underwent reoperation during follow-up period: One patient had
      mitral paravalvular leakage and the other dilatation of the thoracoabdominal
      aorta. CONCLUSIONS: Repair of type A dissection with MR can be performed in a
      single operation. Combined TAR and mitral valve surgery is a much bigger and more
      complex operation associated with high morbidity.

PMID- 25754661
TI  - PRC1 is taking the lead in PcG repression.
AB  - Polycomb group (PcG) proteins constitute a major epigenetic mechanism for gene
      repression throughout the plant life. For a long time, the PcG mechanism has been
      proposed to follow a hierarchical recruitment of PcG repressive complexes (PRCs)
      to target genes in which the binding of PRC2 and the incorporation of H3 lysine
      27 trimethyl marks led to recruitment of PRC1, which in turn mediated H2A
      monoubiquitination. However, recent studies have turned this model upside-down by
      showing that PRC1 activity can be required for PRC2 recruitment and H3K27me3
      marking. Here, we review the current knowledge on plant PRC1 composition and
      mechanisms of repression, as well as its role during plant development. 

PMID- 25754663
TI  - A tribute to the extraordinary career (1964-present) of James Edward Cleaver.

PMID- 25754664
TI  - A bright quantum of time in the Cleaver Laboratory; a tribute and retrospective.

PMID- 25754665
TI  - Long-term influence of bone marrow-derived mesenchymal stem cells on liver
      ischemia-reperfusion injury in a rat model.
AB  - BACKGROUND: The aim of this study was to evaluate the long-term usefulness of
      intraportal injection of the bone marrow-derived mesenchymal stem cells (BM-MSCs)
      in limitation of experimentally induced ischemia-reperfusion injury (IRI) in a
      rat model. MATERIAL AND METHODS: Twenty Wistar rats were divided into 3 groups:
      donor group (n=5), study group (n=10), and control group (n=5). IRI was performed
      using a modified hanging-weight system after left portal triad occlusion in study
      group animals. Isolated autologous BM-MSCs were labeled with fluorochrome PKH-26
      then intraportally injected into the rats in the study group. Control group
      animals were intraportally injected with 1 ml of PBS. Follow-up was 3 months,
      after which animals were sacrificed for histopathological examination. Migration
      of BM-MSCs into different organs was examined. RESULTS: H&E staining of liver
      tissue sections from "time zero" biopsies did not show many irregularities in
      structural or histological construction compared to liver sections from the
      control group. However, a small amount of centrilobular hepatocyte necrosis and
      coagulative necrosis with neutrophil infiltration areas was observed in liver
      sections of the study group. The migration assay of BM-MSCs labeled with PKH-26
      showed the highest positive BM-MSCs staining (6%) in the spleen, while few
      positively stained cells were found (2%) in liver sections. No BM-MSCs were
      detected in brain, kidney, or lung tissues. CONCLUSIONS: These results suggest
      that intraportal bone marrow-derived mesenchymal stem cell injection is safe and
      cells do not migrate chaotically to other organs after targeted implementation.

PMID- 25754666
TI  - Candida-streptococcal mucosal biofilms display distinct structural and virulence
      characteristics depending on growth conditions and hyphal morphotypes.
AB  - Candida albicans and streptococci of the mitis group form communities in multiple
      oral sites, where moisture and nutrient availability can change spatially or
      temporally. This study evaluated structural and virulence characteristics of
      Candida-streptococcal biofilms formed on moist or semidry mucosal surfaces, and
      tested the effects of nutrient availability and hyphal morphotype on dual-species
      biofilms. Three-dimensional models of the oral mucosa formed by immortalized
      keratinocytes on a fibroblast-embedded collagenous matrix were used. Infections
      were carried out using Streptococcus oralis strain 34, in combination with a C.
      albicans wild-type strain, or pseudohyphal-forming mutant strains. Increased
      moisture promoted a homogeneous surface biofilm by C. albicans. Dual biofilms had
      a stratified structure, with streptococci growing in close contact with the
      mucosa and fungi growing on the bacterial surface. Under semidry conditions,
      Candida formed localized foci of dense growth, which promoted focal growth of
      streptococci in mixed biofilms. Candida biofilm biovolume was greater under moist
      conditions, albeit with minimal tissue invasion, compared with semidry
      conditions. Supplementing the infection medium with nutrients under semidry
      conditions intensified growth, biofilm biovolume and tissue invasion/damage,
      without changing biofilm structure. Under these conditions, the pseudohyphal
      mutants and S. oralis formed defective superficial biofilms, with most bacteria
      in contact with the epithelial surface, below a pseudohyphal mass, resembling
      biofilms growing in a moist environment. The presence of S. oralis promoted
      fungal invasion and tissue damage under all conditions. We conclude that
      moisture, nutrient availability, hyphal morphotype and the presence of commensal
      bacteria influence the architecture and virulence characteristics of mucosal
      fungal biofilms.

PMID- 25754667
TI  - Relations between infants' emerging reach-grasp competence and event-related
      desynchronization in EEG.
AB  - Recent reports of similar patterns of brain electrical activity
      (electroencephalogram: EEG) during action execution and observation, recorded
      from scalp locations over motor-related regions in infants and adults, have
      raised the possibility that two foundational abilities--controlling one's own
      intentional actions and perceiving others' actions--may be integrally related
      during ontogeny. However, to our knowledge, there are no published reports of the
      relations between developments in motor skill (i.e. recording actual motor skill
      performance) and EEG during both action execution and action observation. In the
      present study we collected EEG from 21 9-month-olds who were given opportunities
      to reach for toys and who also observed an experimenter reach for toys. Event
      related desynchronization (ERD) was computed from the EEG during the reaching
      events. We assessed infants' reaching-grasping competence, including reach
      latency, errors, preshaping of the hand, and bimanual reaches, and found that
      desynchronization recorded in scalp electrodes over motor-related regions during
      action observation was associated with action competence during execution.
      Infants who were more competent reachers, compared to less competent reachers,
      exhibited greater ERD while observing reaching-grasping. These results provide
      initial evidence for an early emerging neural system integrating one's own
      actions with the perception of others' actions.

PMID- 25754668
TI  - Physical strength and dance attractiveness: Further evidence for an association
      in men, but not in women.
AB  - OBJECTIVES: Physical strength provides information about male quality and can be
      assessed from facial and body morphology. Research on perception of dance
      movements indicates that body movement also provides information about male
      physical strength. These relationships have not been investigated for women.
      METHODS: We investigated relationships of handgrip strength (HGS) and dance
      attractiveness perception in 75 men and 84 women. RESULTS: We identified positive
      relationships between HGS and opposite-sex assessments of dance attractiveness
      for men but not women. CONCLUSIONS: The replication of previous research
      investigating relationships between dance attractiveness and physical strength in
      men corroborates the hypothesis that dance movements provide information about
      male quality. We argue that these relationships are interpretable in contexts of
      inter- and intra-sexual selection.

PMID- 25754669
TI  - Caregiver report versus clinician impression: disagreements in rating
      neuropsychiatric symptoms in Alzheimer's disease patients.
AB  - BACKGROUND: The measurement of neuropsychiatric symptoms (NPS) in dementia is
      often based on caregiver report. Challenges associated with providing care may
      bias the caregiver's recognition and reporting of symptoms. Given potential
      problems associated with caregiver report, clinicians may improve measurement by
      drawing from a wider array of available data and by applying clinical judgment.
      OBJECTIVE: The objective of this study is to evaluate potential disagreements
      between caregiver report and clinician impression when rating psychopathological
      manifestations from the same patient with dementia. METHODS: Three hundred twelve
      participants (156 patients with Alzheimer's disease [AD] and 156 caregivers) were
      studied using the Neuropsychiatric Inventory-Clinician Rating Scale. We
      considered disagreement to be present when caregiver ratings were significantly
      higher or lower (p < 0.05) than NPS ratings by clinicians of the same patient. To
      evaluate whether disagreements were related to dementia severity, we repeated
      comparisons across levels defined by the clinical dementia rating. RESULTS: The
      most common disagreements involved ratings of agitation, depression, anxiety,
      apathy, irritability, and aberrant motor behavior especially in patients with
      mild dementia. There were fewer discrepancies in moderate or severe dementia. The
      most consistent disagreements involved global ratings of depression where
      caregiver scores ranged from +22.5 higher to -4.5 lower than clinician rating.
      CONCLUSIONS: Caregivers may have incomplete perception of patient NPS mainly in
      mild dementia. NPS ratings might be confounded by cultural beliefs, sometimes
      leading caregiver to interpret symptoms as part of "normal" aging.

PMID- 25754671
TI  - Romiplostim promotes platelet recovery in a mouse model of multicycle
      chemotherapy-induced thrombocytopenia.
AB  - Chemotherapy-induced thrombocytopenia can lead to chemotherapy treatment delays
      or dose reductions. The ability of romiplostim, a thrombopoietin (TPO) mimetic,
      to promote platelet recovery in a mouse model of multicycle
      chemotherapy/radiation therapy (CRT)-induced thrombocytopenia was examined. In
      humans, an inverse relationship between platelet counts and endogenous TPO (eTPO)
      concentration exists. In a CRT mouse model, eTPO was not elevated during the
      first 5 days after CRT treatment (the "eTPO gap"), then increased to a peak 10
      days after each CRT treatment in an inverse relationship to platelet counts seen
      in humans. To bridge the eTPO gap, mice were treated with 10-1,000 MUg/kg of
      romiplostim on day 0, 1, or 2 after CRT. In some mice, the romiplostim dose was
      approximately divided over 3 days. Platelet recovery occurred faster with
      romiplostim in most conditions tested. Romiplostim doses of >=100 MUg/kg given on
      day 0 significantly lessened the platelet nadir. Fractionating the dose over 3
      days did not appear to confer a large advantage. These data may provide a
      rationale for clinical studies of romiplostim in chemotherapy-induced
      thrombocytopenia. 

PMID- 25754672
TI  - Extensive phenotypic plasticity of a Red Sea coral over a strong latitudinal
      temperature gradient suggests limited acclimatization potential to warming.
AB  - Global warming was reported to cause growth reductions in tropical shallow water
      corals in both, cooler and warmer, regions of the coral species range. This
      suggests regional adaptation with less heat-tolerant populations in cooler and
      more thermo-tolerant populations in warmer regions. Here, we investigated
      seasonal changes in the in situ metabolic performance of the widely distributed
      hermatypic coral Pocillopora verrucosa along 12 degrees  latitudes featuring a
      steep temperature gradient between the northern (28.5 degrees N, 21-27 degrees C)
      and southern (16.5 degrees N, 28-33 degrees C) reaches of the Red Sea.
      Surprisingly, we found little indication for regional adaptation, but strong
      indications for high phenotypic plasticity: Calcification rates in two seasons
      (winter, summer) were found to be highest at 28-29 degrees C throughout all
      populations independent of their geographic location. Mucus release increased
      with temperature and nutrient supply, both being highest in the south. Genetic
      characterization of the coral host revealed low inter-regional variation and
      differences in the Symbiodinium clade composition only at the most northern and
      most southern region. This suggests variable acclimatization potential to ocean
      warming of coral populations across the Red Sea: high acclimatization potential
      in northern populations, but limited ability to cope with ocean warming in
      southern populations already existing at the upper thermal margin for corals. 

PMID- 25754673
TI  - Altered parasympathetic nervous system regulation of the sinoatrial node in Akita
      diabetic mice.
AB  - Cardiovascular autonomic neuropathy (CAN) is a serious complication of diabetes
      mellitus that impairs autonomic regulation of heart rate (HR). This has been
      attributed to damage to the nerves that modulate spontaneous pacemaker activity
      in the sinoatrial node (SAN). Our objective was to test the hypothesis that
      impaired parasympathetic regulation of HR in diabetes is due to reduced
      responsiveness of the SAN to parasympathetic agonists. We used the Akita mouse
      model of type 1 diabetes to study the effects of the parasympathetic agonist
      carbachol (CCh) on SAN function using intracardiac programmed stimulation, high
      resolution optical mapping and patch-clamping of SAN myocytes. CCh decreased HR
      by 30% and increased corrected SAN recovery time (cSNRT) by 123% in wildtype
      mice. In contrast, CCh only decreased HR by 12%, and only increased cSNRT by 37%
      in Akita mice. These alterations were due to smaller effects of CCh on SAN
      electrical conduction and spontaneous action potential firing in isolated SAN
      myocytes. Voltage clamp experiments demonstrate that the acetylcholine-activated
      K(+) current (IKACh) is reduced in Akita SAN myocytes due to enhanced
      desensitization and faster deactivation kinetics. These IKACh alterations were
      normalized by treating Akita SAN myocytes with PI(3,4,5)P3 or an inhibitor of
      regulator of G-protein signaling 4 (RGS4). There was no difference in the effects
      of CCh on the hyperpolarization-activated current (If) between wildtype and Akita
      mice. Our study demonstrates that Akita diabetic mice demonstrate impaired
      parasympathetic regulation of HR and SAN function due to reduced responses of the
      SAN to parasympathetic agonists. Our experiments demonstrate a key role for
      insulin-dependent phosphoinositide 3-kinase (PI3K) signaling in the
      parasympathetic dysfunction seen in the SAN in diabetes. 

PMID- 25754675
TI  - Whole-genome analysis of pancreatic cancer.

PMID- 25754676
TI  - Medical Innovation Bill terminated.

PMID- 25754677
TI  - Goserelin reduces chemotherapy-associated ovarian failure.

PMID- 25754678
TI  - Charcot-Leyden crystals in acute myeloid leukemia.

PMID- 25754674
TI  - Heart failure with preserved ejection fraction in the elderly: scope of the
      problem.
AB  - Heart failure with preserved ejection fraction (HFpEF) is the most common form of
      heart failure (HF) in older adults, particularly women, and is increasing in
      prevalence as the population ages. With morbidity and mortality on par with HF
      with reduced ejection fraction, it remains a most challenging clinical syndrome
      for the practicing clinician and basic research scientist. Originally considered
      to be predominantly caused by diastolic dysfunction, more recent insights
      indicate that HFpEF in older persons is typified by a broad range of cardiac and
      non-cardiac abnormalities and reduced reserve capacity in multiple organ systems.
      The globally reduced reserve capacity is driven by: 1) inherent age-related
      changes; 2) multiple, concomitant co-morbidities; 3) HFpEF itself, which is
      likely a systemic disorder. These insights help explain why: 1) co-morbidities
      are among the strongest predictors of outcomes; 2) approximately 50% of clinical
      events in HFpEF patients are non-cardiovascular; 3) clinical drug trials in HFpEF
      have been negative on their primary outcomes. Embracing HFpEF as a true geriatric
      syndrome, with complex, multi-factorial pathophysiology and clinical
      heterogeneity could provide new mechanistic insights and opportunities for
      progress in management. This article is part of a Special Issue entitled CV
      Aging. 

PMID- 25754679
TI  - Observations on transatlantic renal cell cancer surgery outcomes.

PMID- 25754680
TI  - Fertility after young-onset colorectal cancer: a study of subjects with Lynch
      syndrome.
AB  - AIM: Infertility is a concern for young survivors of colorectal cancer (CRC), but
      this risk is not well quantified. Carriers of mismatch repair (MMR) mutations are
      a useful cohort for studying fertility after CRC as they commonly develop CRC
      when young, and unaffected family members provide demographically similar
      controls. The aim of this study was to determine the effect of CRC on fertility
      in a large cohort of MMR mutation carriers. METHOD: Mismatch repair mutation
      carriers identified from the Australasian Colorectal Cancer Family Registry were
      included. For each year of life within the fertile age range (15-49), the number
      of living individuals and the number of children born to them were determined.
      Individuals were grouped by whether or not they had had a diagnosis of CRC by
      that age. Age-specific and total fertility rates were calculated. RESULTS: We
      identified 1068 subjects (611 women and 457 men), of whom 467 were diagnosed with
      CRC. There were 1192 births during 18 674 person-years of follow-up to the women
      and 814 births during 14 013 person-years of follow-up to the men. The total
      fertility rate was decreased in women after a diagnosis of CRC compared with
      those who did not have CRC (1.3 vs 2.2; P = 0.0011), but age-specific fertility
      was only reduced in the 20-24-year age group. In men the total fertility rate was
      similar for both groups (2.0 vs 1.8; P = 0.27). CONCLUSION: Age-specific
      fertility was decreased in female CRC survivors with Lynch syndrome aged 20-24,
      but not in older women or in men.

PMID- 25754681
TI  - Orexin-1 receptor signaling increases motivation for cocaine-associated cues.
AB  - The orexin/hypocretin system is involved in multiple cocaine addiction processes
      that involve drug-associated environmental cues, including cue-induced
      reinstatement of extinguished cocaine seeking and expression of conditioned place
      preference. However, the orexin system does not play a role in several behaviors
      that are less cue-dependent, such as cocaine-primed reinstatement of extinguished
      cocaine seeking and low-effort cocaine self-administration. We hypothesized that
      cocaine-associated cues, but not cocaine alone, engage signaling at orexin-1
      receptors (OX1Rs), and this cue-engaged OX1R signaling increases motivation for
      cocaine. Motivation for cocaine was measured in Sprague-Dawley rats with
      behavioral-economic demand curve analysis after pretreatment with the OX1R
      antagonist SB-334867 (SB) or vehicle with and without light + tone cues. Demand
      for cocaine was higher when cocaine-associated cues were present, and SB only
      reduced cocaine demand in the presence of these cues. We then investigated
      whether cocaine demand was linked to the cued reinstatement of cocaine seeking,
      as both procedures are partially driven by cocaine-associated cues in an orexin
      dependent manner. SB blocked cue-induced reinstatement behavior, and baseline
      demand predicted SB efficacy with the largest effect in high-demand animals, i.e.
      animals with the greatest cue-dependent behavior. We conclude that OX1R signaling
      increases the reinforcing efficacy of cocaine-associated cues but not that of
      cocaine alone. This supports our view that orexin plays a prominent role in the
      ability of conditioned cues to activate motivational responses. 

PMID- 25754682
TI  - A novel TGM1 mutation, leading to multiple splicing rearrangements, is associated
      with autosomal recessive congenital ichthyosis.
AB  - Autosomal recessive congenital ichthyosis (ARCI) is a group of rare, clinically
      heterogeneous skin disorders that affect cornification. ARCI includes lamellar
      ichthyosis, congenital ichthyosiform erythroderma and harlequin ichthyosis. TGM1
      mutations cause > 50% of ARCI cases in the USA. We report two siblings with ARCI.
      They were found to carry a novel aetiological TGM1 mutation, which leads to the
      synthesis of multiple abnormal transcripts. These molecules resulted from three
      independent mechanisms: intron retention, exon skipping and activation of expand
      cryptic splice sites. Taken together, our findings expand the known TGM1 mutation
      repertoire, and provide an insight into the molecular mechanisms leading to ARCI
      phenotypes. These results could be useful for genetic counselling and future
      potential genotype-phenotype correlations. 

PMID- 25754683
TI  - A novel hydroxamic acid-containing antibiotic produced by a Saharan soil-living
      Streptomyces strain.
AB  - During screening for potentially antimicrobial actinobacteria, a highly
      antagonistic strain, designated WAB9, was isolated from a Saharan soil of
      Algeria. A polyphasic approach characterized the strain taxonomically as a member
      of the genus Streptomyces. The strain WAB9 exhibited a broad spectrum of
      antimicrobial activity toward various multidrug-resistant micro-organisms. A PCR
      based assay of genomic potential for producing bioactive metabolites revealed the
      presence of PKS-II gene. After 6 days of strain fermentation, one bioactive
      compound was extracted from the remaining aqueous phase and then purified by
      HPLC. The chemical structure of the compound was determined by spectroscopic (UV
      visible, and (1)H and (13)C NMR) and spectrometric analysis. The compound was
      identified to be 2-amino-N-(2-amino-3-phenylpropanoyl)-N-hydroxy-3
      phenylpropanamide, a novel hydroxamic acid-containing molecule. The pure molecule
      showed appreciable minimum inhibitory concentration values against a selection of
      drug-resistant bacteria, filamentous fungi and yeasts. Significance and impact of
      the study: This study presents the isolation of a Streptomyces strain, named
      WAB9, from a Saharan soil in Algeria. This strain was found to produce a new
      hydroxamic acid-containing molecule with interesting antimicrobial activities
      towards various multidrug-resistant micro-organisms. Although hydroxamic acid
      containing molecules are known to exhibit low toxicities in general, only real
      evaluations of the toxicity levels could decide on the applications for which
      this new molecule is potentially most appropriate. Thus, this article provides a
      new framework of research.

PMID- 25754684
TI  - Substance Use, Offending, and Participation in Alcohol and Drug Treatment
      Programmes: A Comparison of Prisoners with and without Intellectual Disabilities.
AB  - BACKGROUND: Many offenders with intellectual disabilities have substance use
      issues. Offending behaviour may be associated with substance use. MATERIALS AND
      METHODS: Prisoners with and without intellectual disabilities were compared in
      terms of their substance use prior to imprisonment, the influence of substance
      use on offending, and their participation in alcohol and drug treatment
      programmes. RESULTS: Substance use was similar in prisoners with and without
      intellectual disabilities in the year prior to their current prison terms.
      Prisoners with intellectual disabilities were much less likely to report that
      substance use was an antecedent to the offences leading to their imprisonment.
      The completion rate of alcohol and drug treatment programmes was much lower for
      those with intellectual disabilities. CONCLUSIONS: Substance use may be as common
      in prisoners with intellectual disabilities as those without this condition.
      Services may need to reflect on whether their treatment programmes are meeting
      the needs of all prisoners.

PMID- 25754685
TI  - Direct control of the temperature rise in parallel transmission by means of
      temperature virtual observation points: Simulations at 10.5 Tesla.
AB  - PURPOSE: A method using parallel transmission to mitigate B1+ inhomogeneity while
      explicitly constraining the temperature rise is reported and compared with a more
      traditional SAR-constrained pulse design. METHODS: Finite difference time domain
      simulations are performed on a numerical human head model and for a 16-channel
      coil at 10.5 Tesla. Based on a set of presimulations, a virtual observation point
      compression model for the temperature rise is derived. This compact
      representation is then used in a nonlinear programming algorithm for pulse design
      under explicit temperature rise constraints. RESULTS: In the example of a time-of
      flight sequence, radiofrequency pulse performance in some cases is increased by a
      factor of two compared with SAR-constrained pulses, while temperature rise is
      directly and efficiently controlled. Pulse performance can be gained by relaxing
      the SAR constraints, but at the expense of a loss of direct control on
      temperature. CONCLUSION: Given the importance of accurate safety control at
      ultrahigh field and the lack of direct correspondence between SAR and
      temperature, this work motivates the need for thorough thermal studies in normal
      in vivo conditions. The tools presented here will possibly contribute to safer
      and more efficient MR exams.

PMID- 25754687
TI  - Decomposing the effect of crime on population changes.
AB  - This article estimates the effect of crime on migration rates for counties in
      U.S. metropolitan areas and makes three contributions to the literature. First, I
      use administrative data on migration flows between counties, which gives me more
      precise estimates of population changes than data used in previous studies.
      Second, I am able to decompose net population changes into gross migration flows
      in order to identify how individuals respond to crime rate changes. Finally, I
      include county-level trends so that my identification comes from shocks away from
      the trend. I find effects that are one-fiftieth the size of the most prominent
      estimate in the literature; and although the long-run effects are somewhat
      larger, they are still only approximately one-twentieth as large. I also find
      that responses to crime rates differ by subgroups, and that increases in crime
      cause white households to leave the county, with effects almost 10 times as large
      as for black households. 

PMID- 25754686
TI  - Reduction in cervical intraepithelial neoplasia in young women in British
      Columbia after introduction of the HPV vaccine: An ecological analysis.
AB  - We report on the rates of cervical intraepithelial neoplasia (CIN) in young women
      aged 15-22 years of age in British Columbia before and after the introduction of
      an HPV vaccine program. Rates of cervical intraepithelial neoplasia (CIN) 2+ for
      each age stratum (15-22) in the calendar years 2004-2012 for the province of
      British Columbia were obtained from the BC Cancer Agency's population-based
      cervical cancer program. Incidence rate ratios (IRR) of CIN2+ were described and
      compared before and after HPV vaccine program introduction in cohorts born in
      vaccine eligible years, and in non-vaccine eligible years using piece-wise
      Poisson regression analysis, and adjusted for age. Between 2004 and 2012, rates
      of CIN2 and CIN2+ in young women aged 15-22 years in the province of British
      Columbia have decreased overall. After the introduction of the HPV vaccine
      program, the age adjusted IRR for CIN2+ for young women aged 15-17 years
      decreased significantly from 0.91 (95% CI: 0.86-0.98 p < 0.01) to 0.36 (95% CI:
      0.18-0.73 p < 0.01). During the same time period, no similar reduction was found
      in young women 18-22 years. After introduction of HPV vaccine program, IRR for
      CIN2+ in young women 15-17 was significantly reduced for CIN2+ (0.14; 95% CI:
      0.04- 0.47; p < 0.01) and CIN2 (0.1; 95% CI: 0.02-0.54; p < 0.01). This
      ecological analysis shows a significant reduction in CIN2+ lesions in young women
      aged 15-17 years in British Columbia after the introduction of the HPV vaccine in
      young women despite vaccine uptake levels below 70%. 

PMID- 25754688
TI  - Brain structure characteristics in intellectually superior schizophrenia.
AB  - The current study aims to fill a gap in the knowledge base by investigating the
      structural brain characteristics of individuals with schizophrenia and superior
      intellectual abilities. Subcortical volumes, cortical thickness and cortical
      surface area were examined in intellectually normal and intellectually superior
      participants with schizophrenia and their IQ-matched healthy controls, as well as
      in intellectually low schizophrenia participants. We replicated significant
      diagnostic group effects on hippocampal and ventricular size after correction for
      multiple comparisons. There were no statistically significant effects of
      intellectual level or of the interaction between diagnostic group and
      intellectual level. Effect sizes indicated that differences between schizophrenia
      and healthy control participants were of similar magnitude at both intellectual
      levels for all three types of morphological data. A secondary analysis within the
      schizophrenia group, including participants with low intellectual abilities,
      yielded numerical, but no statistically significant differences on any structural
      brain measure. The present findings indicate that the brain structure
      abnormalities in schizophrenia are present at all intellectual levels, and
      individuals with schizophrenia and superior intellectual abilities have brain
      structure abnormalities of the same magnitude as individuals with schizophrenia
      and normal intellectual abilities. 

PMID- 25754689
TI  - Predicting 3-year survival in older people with intellectual disabilities using a
      Frailty Index.
AB  - OBJECTIVES: To analyze the relationship between frailty and survival in older
      people with intellectual disabilities (IDs). DESIGN: Population-based
      longitudinal observational study. SETTING: Three Dutch care provider services.
      PARTICIPANTS: Individuals with borderline to profound ID aged 50 and older
      (N=982). MEASUREMENTS: A frailty index (FI) including 51 health-related deficits
      was used to measure frailty. Mean follow-up was 3.3 years. The Cox proportional
      hazards model was used to evaluate the independent effect of frailty on survival.
      The discriminative ability of the FI was measured using a receiver operating
      characteristic (ROC) curve. RESULTS: Greater FI values were associated with
      greater risk of death, independent of sex, age, level of ID, and Down syndrome.
      There was a nonlinear increase in risk with increasing FI value. For example,
      mortality risk was 2.17 times as great (95% confidence interval (CI)=0.95-4.95)
      for vulnerable individuals (FI 0.20-0.29) and 19.5 (95% CI=9.13-41.8) times as
      great for moderately frail individuals (FI 0.40-0.49) as for relatively fit
      individuals (FI<0.20). The area under the ROC curve for 3-year survival was 0.78.
      CONCLUSION: Although the predictive validity of the FI should be further
      determined, it was strongly associated with 3-year mortality. Care providers
      working with people with ID should be able to recognize frail clients and act in
      an early stage to stop or prevent further decline.

PMID- 25754690
TI  - Attenuation of cardiac hypertrophy by G-CSF is associated with enhanced migration
      of bone marrow-derived cells.
AB  - Granulocyte-colony stimulating factor (G-CSF) has been shown to promote
      mobilization of bone marrow-derived stem cells (BMCs) into the bloodstream
      associated with improved survival and cardiac function after myocardial
      infarction. Therefore, the aim of the present study was to investigate whether G
      CSF is able to attenuate cardiac remodelling in a mouse model of pressure-induced
      LV hypertrophy focusing on mobilization and migration of BMCs. LV hypertrophy was
      induced by transverse aortic constriction (TAC) in C57BL/6J mice. Four weeks
      after TAC procedure. Mice were treated with G-CSF (100 MUg/kg/day; Amgen
      Biologicals) for 2 weeks. The number of migrated BMCs in the heart was analysed
      by flow cytometry. mRNA expression and protein level of different growth factors
      in the myocardium were investigated by RT-PCR and ELISA. Functional analyses
      assessed by echocardiography and immunohistochemical analysis were performed 8
      weeks after TAC procedure. G-CSF-treated animals revealed enhanced homing of VLA
      4(+) and c-kit(+) BMCs associated with increased mRNA expression and protein
      level of the corresponding homing factors Vascular cell adhesion protein 1 and
      Stem cell factor in the hypertrophic myocardium. Functionally, G-CSF
      significantly preserved LV function after TAC procedure, which was associated
      with a significantly reduced area of fibrosis compared to control animals.
      Furthermore, G-CSF-treated animals revealed a significant improvement of survival
      after TAC procedure. In summary, G-CSF treatment preserves cardiac function and
      is able to diminish cardiac fibrosis after induction of LV hypertrophy associated
      with increased homing of VLA-4(+) and c-kit(+) BMCs and enhanced expression of
      their respective homing factors VCAM-1 and SCF. 

PMID- 25754691
TI  - Midterm follow-up after retrievable inferior vena cava filter placement in venous
      thromboembolism patients with or without malignancy.
AB  - BACKGROUND: A clear indication and strategy for placement of retrievable inferior
      vena cava filters (IVCFs) have not been established. This study was designed to
      evaluate the efficacy and disadvantages of the retrievable IVCF use particularly
      in venous thromboembolism (VTE) patients with malignancy. HYPOTHESIS: Retrievable
      IVCFs might be safe and useful in VTE patients with malignancy. METHODS: The
      study population consisted of 56 consecutive patients undergoing IVCF placement
      at our institution from January 1, 2008 to December 31, 2011. Prognostic data
      were retrospectively reviewed in April 2013. RESULTS: Mean follow-up period was
      584.6 (range, 1-1857) days. Twenty-six of the 56 patients had a malignancy. In 16
      of the 30 patients without malignancy, the filter was retrieved, whereas the
      other 14 patients eventually received permanent implantation. There was no
      significant difference in the survival rate between the retrieval group and the
      nonretrieval group in the nonmalignancy patients (1-year survival rates, 94% vs
      85%). In patients with malignancy, the nonretrieval group showed a significantly
      lower survival rate (P < 0.01). The 1-year and 2-year survival rates were 100% vs
      46% and 100% vs 18%, respectively. There was no medical record of pulmonary
      thromboembolism occurrence or recurrence. All deaths in the patients with
      malignancy were malignancy related. In 4 of 5 malignancy patients who could
      undergo tumor resection surgery, adequate thrombus regression enabled us to
      retrieve the IVCF after surgery. CONCLUSIONS: Permanent use of a retrievable IVCF
      is relatively safe in short- or midterm follow-up regardless of malignancy
      status. Retrievable filter use might be reasonable in malignancy patients.

PMID- 25754692
TI  - Simultaneous Determination of Fangchinoline and Tetrandrine in Qi-Fang-Xi-Bi
      Granules by RP-HPLC.
AB  - Knee Osteoarthritis is one of the most common diseases of elder worldwide. Qi
      Fang-Xi-Bi-Granules (QFXBG) is a new Chinese medicine granules employed for the
      treatment of Knee Osteoarthritis. Fangchinoline (FAN) and tetrandrine (TET) are
      used as targets of quality control of QFXBG. A simple, practical high-performance
      liquid chromatographic method was developed for the simultaneous quantitation of
      FAN and TET in Stephaniae tetrandrae radix and QFXBG. The analysis was performed
      on a Athena C18 column (250 * 4.6 mm, 5 um) with mobile phase of methanol-water
      (65 : 35, v/v, pH 3.0, adjusted by glacial acetic acid) containing 1.0 g/L sodium
      1-octanesulfonate. This method was validated in terms of linearity, precision,
      accuracy and recovery. Results showed that this method had good linearity with
      R(2) at >0.999. The limit of detection and limit of quantification for FAN were
      0.13 and 0.35 mg/L, while for TET were 0.28 and 0.76 mg/L, respectively. The
      relative standard deviations of precision were 0.1-1.3% for intraday and 0.5-2.4%
      for interday. The recovery was 94.56-98.81% of FAN and 94.07-99.12% of TET,
      respectively. The chromatographic analytical time was 14 min. This method was
      successfully applied for the quantitative analysis of FAN and TET in Stephaniae
      tetrandrae radix and QFXBG, so that it could be extended to quality control of
      QFXGB in commercial. 

PMID- 25754693
TI  - A rapid HPLC method for determination of zolpidem and its degradation product in
      tablets using a monolithic column.
AB  - A simple, accurate reverse phase high-performance liquid chromatographic method,
      utilizing a monolithic silica column, for determination of zolpidem hemitartrate
      and its degradation product in tablet dosage form was developed. Analysis was
      achieved on the monolithic, C18 (100 mm, 3.9 mm) column, in isocratic mode with
      acetonitrile-NaH2PO4 (pH 7.0; 0.01 M; 35:65, v/v) as mobile phase and a flow rate
      of 2.5 mL/min at room temperature with UV detection at 245 nm. Diazepam was
      applied as an internal standard. The retention time of zolpidem and its
      degradation product was 2.14 and 1.89, respectively. Calibration curve was linear
      in the range of 0.12-5 ug/mL and the recovery values were found to be 97-101%.
      The limit of quantitation was determined 0.12 MUg/mL. The relative standard
      deviation values of intraday and interday studies were calculated as 0.13-1.1%
      and 0.54-1.3%, respectively. 

PMID- 25754694
TI  - A Case of Contested Cremains Analyzed Through Metric and Chemical Comparison.
AB  - Since the 1980s, cremation has become the fastest growing area of the U.S.
      funeral industry. At the same time, the number of litigations against funeral
      homes and cremation facilities has increased. Forensic anthropologists are often
      asked to determine whether the contents of an urn are actually cremated bone, and
      to address questions regarding the identity of the remains. This study uses both
      metric and chemical analyses for resolving a case of contested cremains. A
      cremains weight of 2021.8 g was predicted based on the decedent's reported
      stature and weight. However, the urn contents weighed 4173.5 g. The urn contents
      also contained material inconsistent with cremains (e.g., moist sediment, stones,
      ferrous metal). Analysis using XRD and SEM demonstrated that the urn contained
      thermally altered bone as well as inorganic material consistent with glass fiber
      cement. Although forensically challenging, cremains cases such as this one can be
      resolved using a multidisciplinary approach. 

PMID- 25754695
TI  - Improving survival in cerebral palsy: where do we go from here?

PMID- 25754696
TI  - Dual-axis hormonal covariation in adolescence and the moderating influence of
      prior trauma and aversive maternal parenting.
AB  - Adversity early in life can disrupt the functioning of the hypothalamic-pituitary
      adrenal and hypothalamic-pituitary-gonadal axes and increase risk for negative
      health outcomes. The interplay between these axes and the environment is complex,
      and understanding needs to be advanced by the investigation of the multiple
      hormonal relationships underlying these processes. The current study examined
      basal hormonal associations between morning levels of cortisol, testosterone, and
      dehydroepiandrosterone in a cohort of adolescents (mean age 15.56 years). The
      moderating influence of childhood adversity was also examined, as indexed by self
      reported trauma (at mean age 14.91), and observed maternal aggressive parenting
      (at mean age 12.41). Between-person regressions revealed significant associations
      between hormones that were moderated by both measures of adversity. In females,
      all hormones positively covaried, but also interacted with adversity, such that
      positive covariation was typically only present when levels of trauma and/or
      aggressive parenting were low. In males, hormonal associations and interactions
      were less evident; however, interactions were detected for cortisol-testosterone 
      positively covarying at high levels of aggressive parenting but negatively
      covarying at low levels - and DHEA-cortisol - similarly positively covarying at
      high levels of parental aggression. These results demonstrate associations
      between adrenal and gonadal hormones and the moderating role of adversity, which
      is likely driven by feedback mechanisms, or cross-talk, between the axes. These
      findings suggest that hormonal changes may be the pathway through which early
      life adversity alters physiology and increases health risks, but does so
      differentially in the sexes; however further study is necessary to establish
      causation.

PMID- 25754697
TI  - Biological therapies for psoriasis: Adherence and outcome analysis from a
      clinical perspective.
AB  - We evaluated and compared patients' long-term adherence to biological therapies
      in a real-life clinical setting. Secondary aims included weight changes on
      biological therapy and reporting adverse effects. This prospective case-note
      review included 58 patients, undergoing 84 treatment series including etanercept
      (21), adalimumab (24), infliximab (14) and ustekinumab (25). Patients' adherence
      was greatest with ustekinumab (being 6.7-fold less likely to withdraw from
      treatment than etanercept, P = 0.014), while the difference in treatment
      adherence of adalimumab and infliximab compared to etanercept was not
      statistically significant. Adalimumab and infliximab were associated with an
      increase in weight, while ustekinumab was associated with weight loss compared
      with etanercept (not statistically significant). Long-term patient adherence to
      biologic therapy in patients with psoriasis is greatest with ustekinumab. 

PMID- 25754698
TI  - Effects of natural organic matter on the coprecipitation of arsenic with iron.
AB  - Natural organic matter (NOM) can affect arsenic speciation and mobility in the
      environment. In this study, the effects of NOM on the coprecipitation of arsenic
      with iron were investigated in order to better understand the fate and transport
      of arsenic in natural environments. The coprecipitation of arsenic with iron was
      studied in the presence and absence of NOM under various arsenic-to-iron molar
      ratios (As/Fe) and pH conditions. The addition of humic acid (HA) hindered the As
      Fe coprecipitation under high pH and high As/Fe conditions by forming a soluble
      As-Fe-HA complex. The X-ray diffraction and Fourier transform infrared studies
      showed that the As-Fe-coprecipitated solid phase was highly affected by pH and
      As/Fe. The arsenic was coprecipitated with iron as an amorphous ferric arsenate
      phase at a low pH level or high As/Fe conditions, while the formation of
      ferrihydrite phase and the arsenic incorporation to the ferrihydrite by
      adsorption was predominant at high pH levels or low As/Fe conditions. The HA
      affected the As-Fe-coprecipitated solid phase depending on the As/Fe molar ratio
      under neutral and alkaline conditions. 

PMID- 25754699
TI  - Ultrafiltration, a useful method for isolation of intermediates in native
      chemical ligation exemplified with the total synthesis of Sortase ADeltaN59.
AB  - In this paper, ultrafiltration was employed to facilitate the isolation of
      intermediates in native chemical ligation. Depending on the molecular weight
      cutoff of the membrane used, molecules with different sizes could be purified,
      separated, or concentrated by the ultrafiltration process. Total chemical
      synthesis of the polypeptide chain of the enzyme Sortase ADeltaN59 was used as an
      example of the application of ultrafiltration in chemical protein synthesis.
      Sortase A is a ligase that catalyzes transpeptidation reactions between proteins
      that have C-terminal LPXTG recognition sequence and Gly5- on the peptidoglycan of
      bacterial cell walls. Ultrafiltration technique facilitated synthesis of Sortase
      ADeltaN59 and was a promising tool in isolation of intermediates in native
      chemical ligation.

PMID- 25754700
TI  - Epigenetic biomarker to support classification into pluripotent and non
      pluripotent cells.
AB  - Quality control of human induced pluripotent stem cells (iPSCs) can be performed
      by several methods. These methods are usually relatively labor-intensive,
      difficult to standardize, or they do not facilitate reliable quantification.
      Here, we describe a biomarker to distinguish between pluripotent and non
      pluripotent cells based on DNA methylation (DNAm) levels at only three specific
      CpG sites. Two of these CpG sites were selected by their discriminatory power in
      258 DNAm profiles - they were either methylated in pluripotent or non-pluripotent
      cells. The difference between these two beta-values provides an Epi-Pluri-Score
      that was validated on independent DNAm-datasets (264 pluripotent and 1,951 non
      pluripotent samples) with 99.9% specificity and 98.9% sensitivity. This score was
      complemented by a third CpG within the gene POU5F1 (OCT4), which better
      demarcates early differentiation events. We established pyrosequencing assays for
      the three relevant CpG sites and thereby correctly classified DNA of 12
      pluripotent cell lines and 31 non-pluripotent cell lines. Furthermore, DNAm
      changes at these three CpGs were tracked in the course of differentiation of
      iPSCs towards mesenchymal stromal cells. The Epi-Pluri-Score does not give
      information on lineage-specific differentiation potential, but it provides a
      simple, reliable, and robust biomarker to support high-throughput classification
      into either pluripotent or non-pluripotent cells. 

PMID- 25754701
TI  - Multiple facial basal cell carcinomas in xeroderma pigmentosum treated with
      topical imiquimod 5% cream.
AB  - Xeroderma pigmentosum (XP) is an autosomal recessive disease characterized by
      solar sensitivity, photophobia, early onset of freckling, and solar-induced
      cutaneous neoplastic changes. Management of patients with XP is a therapeutic
      challenge as they usually develop multiple cutaneous malignancies, making
      surgical therapy difficult, and continue to form skin malignancies at a high
      rate. We describe a 30-year-old Chinese man with XP who had been previously
      treated with excision and dermatoplasty. Upon recurrence of multiple superficial,
      ulcerative, and pigmented lesions, imiquimod 5% cream was recommended for 4
      months. His multiple facial lesions demonstrated an excellent response to topical
      imiquimod 5% cream with minor side effects. This favorable response indicates
      that topical application of imiquimod 5% cream is an effective means of treating
      multiple basal cell carcinomas in XP. 

PMID- 25754702
TI  - Koplik spots revisited.

PMID- 25754703
TI  - Societal preferences for the return of incidental findings from clinical genomic
      sequencing: a discrete-choice experiment.
AB  - BACKGROUND: An important challenge with the application of next-generation
      sequencing technology is the possibility of uncovering incidental genomic
      findings. A paucity of evidence on personal utility for incidental findings has
      hindered clinical guidelines. Our objective was to estimate personal utility for
      complex information derived from incidental genomic findings. METHODS: We used a
      discrete-choice experiment to evaluate participants' personal utility for the
      following attributes: disease penetrance, disease treatability, disease severity,
      carrier status and cost. Study participants were drawn from the Canadian public.
      We analyzed the data with a mixed logit model. RESULTS: In total, 1200
      participants completed our questionnaire (available in English and French).
      Participants valued receiving information about high-penetrance disorders but
      expressed disutility for receiving information on low-penetrance disorders. The
      average willingness to pay was $445 (95% confidence interval [CI] $322-$567) to
      receive incidental findings in a scenario where clinicians returned information
      about high-penetrance, medically treatable disorders, but only 66% of
      participants (95% CI 63%-71%) indicated that they would choose to receive
      information in that scenario. On average, participants placed an important value
      ($725, 95% CI $600-$850) on having a choice about what type of findings they
      would receive, including receipt of information about high-penetrance, treatable
      disorders or receipt of information about high-penetrance disorders with or
      without available treatment. The predicted uptake of that scenario was 76% (95%
      CI 72%-79%). INTERPRETATION: Most participants valued receiving incidental
      findings, but personal utility depended on the type of finding, and not all
      participants wanted to receive incidental results, regardless of the potential
      health implications. These results indicate that to maximize benefit, participant
      level preferences should inform the decision about whether to return incidental
      findings.

PMID- 25754704
TI  - Medical aid adapts to increasing violence.

PMID- 25754706
TI  - Carter v. Canada: what's next for physicians?

PMID- 25754707
TI  - Label changes conflict with WHO sugar advice.

PMID- 25754708
TI  - A real sting in the tail.

PMID- 25754709
TI  - E-cigarettes more popular than tobacco among youth.

PMID- 25754710
TI  - Canada's reproduction law will have trouble accommodating emerging science.

PMID- 25754711
TI  - McKittrick-Wheelock syndrome.

PMID- 25754712
TI  - Imagined interiors.

PMID- 25754713
TI  - New insights into phase distribution, phase composition and disorder in
      Y2(Zr,Sn)2O7 ceramics from NMR spectroscopy.
AB  - A combination of (89)Y and (119)Sn NMR spectroscopy and DFT calculations are used
      to investigate phase evolution, local structure and disorder in Y2Zr2-xSnxO7
      ceramics, where a phase change is predicted, from pyrochlore to defect fluorite,
      with increasing Zr content. The ability of NMR to effectively probe materials
      that exhibit positional and compositional disorder provides insight into the
      atomic-scale structure in both ordered and disordered phases and, by exploiting
      the quantitative nature of the technique, we are able to determine detailed
      information on the composition of the phase(s) present and the average
      coordination number (and next-nearest neighbour environment) of the cations. In
      contrast to previous studies, a more complex picture of the phase variation with
      composition emerges, with single-phase pyrochlore found only for the Sn end
      member, and a single defect fluorite phase only for x = 0 to 0.6. A broad two
      phase region is observed, from x = 1.8 to 0.8, but the two phases present have
      very different composition, with a maximum of 13% Zr incorporated into the
      pyrochlore phase, whereas the composition of the defect fluorite phase varies
      throughout. Preferential ordering of the anion vacancies in the defect fluorite
      phase is observed, with Sn only ever found in a six-coordinate environment, while
      remaining vacancies are shown to be more likely to be associated with Zr than Y.
      Our findings are then discussed in the light of those from previous studies, many
      of which utilize diffraction-based approaches, where, in most cases, a single
      phase of fixed composition has been assumed for the refinement procedure. The
      significant and surprising differences encountered demonstrate the need for
      complementary approaches to be considered for a detailed and accurate picture of
      both the long- and short-range structure of a solid to be achieved. 

PMID- 25754714
TI  - Symptoms and physiological responses to prolonged, repeated, low-level tooth
      clenching in humans.
AB  - BACKGROUND: The traditional view contends bruxism, such as tooth
      grinding/clenching, is part of the etiology of temporomandibular disorders (TMD)
      including some subtypes of headaches. The purpose of this study is to investigate
      if a low-level but long-lasting tooth-clenching task initiates TMD
      symptoms/signs. METHODS: Eighteen healthy participants (mean age +/- SD, 24.0 +/-
      4.3 years) performed and repeated an experimental 2-hour tooth-clenching task at
      10% maximal voluntary occlusal bite force at incisors (11.1 +/- 4.6 N) for three
      consecutive days (Days 1-3). Pain and cardiovascular parameters were estimated
      during the experiment. RESULTS: The task evoked pain in the masseter/temporalis
      muscles and temporomandibular joint after 40.0 +/- 18.0 minutes with a peak
      intensity of 1.6 +/- 0.4 on 0-10 numerical rating scale (NRS) after 105.0 +/- 5.0
      minutes (Day 1). On Day 2 and Day 3, pain had disappeared but the tasks, again,
      evoked pain with similar intensities. The onset and peak levels of pain were not
      different between the experimental days (P = .977). However, the area under the
      curve of pain NRS in the masseter on Day 2 and Day 3 were smaller than that on
      Day 1 (P = .006). Cardiovascular parameters changed during the task but not
      during the days. CONCLUSIONS: Prolonged, low-level tooth clenching evoked short
      lived pain like TMD. This intervention study proposes that tooth clenching alone
      is insufficient to initiate longer lasting and self-perpetuating symptoms of TMD,
      which may require other risk factors.

PMID- 25754715
TI  - Education status determines 10-year (2002-2012) survival from cardiovascular
      disease in Athens metropolitan area: the ATTICA study, Greece.
AB  - Cardiovascular disease (CVD) remains the leading cause of morbidity and mortality
      worldwide, and educational level seems to be an important determinant of the
      disease occurrence. The aim of this work was to investigate the association
      between education status and 10-year incidence of CVD, controlling for various
      socio-demographic lifestyle and clinical factors. From May 2001 to December 2002,
      1514 men and 1528 women (>18 years) without any clinical evidence of CVD or any
      other chronic disease, at baseline, living in greater Athens area, Greece, were
      enrolled. In 2011-2012, the 10-year follow-up was performed in 2583 participants
      (15% of the participants were lost to follow-up). Incidence of fatal or non-fatal
      CVD was defined according to WHO-ICD-10 criteria. Education status was measured
      in years of schooling. The 10-year incidence of CVD was 15.7% [95% confidence
      intervals (CI) 14.1%-17.4%], 19.7% in men and 11.7% in women (Pgender < 0.001).
      Age-and gender-adjusted analyses revealed that those with low education (<9 years
      of schooling) were 1.52 times more likely (95% CI 1.03-2.23%) to have CVD
      compared with those with high education (>12 years of schooling). People in the
      low education group had higher prevalence of hypertension, diabetes and
      dyslipidaemias, were more likely to be smokers and sedentary, had less healthy
      dietary habits, as compared with those in the high education group. When
      controlling for participants' medical history, smoking, dietary and lifestyle
      habits, low education was no longer significantly associated with CVD,
      illustrating the mediating effect of clinical and behavioural factors in the link
      between education and disease. It was of interest that low education status
      interacted with alcohol drinking, enhancing the adverse effect of low education
      on CVD risk (relative risk 1.44, 95% CI 0.94%-2.20%), after various adjustments
      made. In this study, it was concluded that low educational level was associated
      with increased CVD risk. This was mainly explained by the intermediate
      association of low education with unhealthy choices that consequently worsen
      clinical status.

PMID- 25754716
TI  - Biologics in asthma--the next step toward personalized treatment.
AB  - Asthma is a multifaceted disease and is associated with significant impairment
      and risk, and a therapeutic response that is highly variable. Although current
      treatments are usually effective for patients with mild-to-moderate disease,
      patients with more severe asthma are often unresponsive to current efforts, and
      there remains a need for agents with properties that may achieve control in these
      individuals. There is ongoing research to identify bioactive molecules that
      contribute to the pathophysiology of asthma, and many of these have been
      identified as potential therapeutic targets to improve control of this disease.
      As a consequence of these efforts, monoclonal antibodies have been developed and
      tested as to their effectiveness in the treatment of asthma. The assessment of
      these new treatments has identified particular pathways that, in selected
      patients, have shown benefit. The following review will discuss the current and
      future use of biological agents for the treatment of asthma, their efficacy, and
      how certain patient phenotypes and endotypes may be associated with biomarkers
      that may be used to select treatments to achieve greatest effectiveness of their
      use. As knowledge of the effects of these biological agents in asthma emerges, as
      well as the patients in whom they are most beneficial, the movement toward
      personalized treatment will follow. 

PMID- 25754717
TI  - Biologic therapies targeting eosinophils: current status and future prospects.
AB  - The recent explosion in the number of biologic therapies in clinical development
      for the treatment of eosinophilic disorders is unprecedented. As these agents
      become available for clinical use, the selection of the most appropriate agent
      for a given patient will become increasingly complicated. The aims of this review
      were 2-fold: (1) to present the lessons learned from clinical trials using the
      first generation of eosinophil-targeted biologics (anti-IL-5 antibodies) and (2)
      to discuss the advantages and potential limitations of currently available and
      novel targeted therapies to treat eosinophilic disorders. 

PMID- 25754718
TI  - Hypersensitivity to biological agents-updated diagnosis, management, and
      treatment.
AB  - Biological agents are used in the treatment of neoplastic, autoimmune, and
      inflammatory diseases and their clinical applications are becoming broader.
      Following their increased utilization, hypersensitivity reactions linked to these
      drugs have become more frequent, sometimes preventing the use of first-line
      therapies. The clinical presentation of hypersensitivity reactions to biological
      agents ranges from mild cutaneous manifestations to life-threatening reactions.
      In this scenario, rapid desensitization is a groundbreaking procedure that
      enables selected patients to receive the full treatment dose in a safe way, in
      spite of their immediate hypersensitivity reaction to the drug, and protects them
      against anaphylaxis. The aim of this review is to update and discuss some of the
      main biological agents used in clinical practice (rituximab, trastuzumab,
      cetuximab, ofatumumab, tocilizumab, brentuximab, omalizumab, and tumor necrosis
      factor alpha inhibitor agents) and their associated hypersensitivity reactions,
      including clinical presentations, diagnosis, and treatment in the acute setting.
      In addition, novel management options with rapid desensitization are presented. 

PMID- 25754719
TI  - Evaluation of allergen immunotherapy.

PMID- 25754720
TI  - TeleAllergy: a new way to manage asthma.

PMID- 25754721
TI  - Hypereosinophilic disorders.

PMID- 25754722
TI  - Itching without a rash.

PMID- 25754723
TI  - Intranasal live-attenuated influenza vaccine (LAIV) is unlikely to cause egg
      mediated allergic reactions in egg-allergic children.

PMID- 25754724
TI  - Acute and repeated dose toxicity studies of different beta-cyclodextrin-based
      nanosponge formulations.
AB  - Nanosponges (NS) show promising results in different fields such as medicine,
      agriculture, water purification, fire engineering and so on. The present study
      was designed to evaluate toxicity of different NS formulations (namely, S1-S6)
      synthesized with different cross-linking agents such as carbonyl diimidazole,
      pyromellitic dianhydride and hexamethylene diisocynate; and preparation methods
      in experimental animals. Acute and repeated dose toxicity studies of formulations
      were carried out as per OECD guidelines 423 and 407, respectively. For acute
      toxicity study, formulations were administered to female rats at doses of 300 and
      2000 mg/kg orally. The general behaviour of the rats was continuously monitored
      for 1 h after dosing, periodically during the first 24 h and daily thereafter for
      a total of 14 days. On day 14, animals were fasted overnight, weighed, and
      sacrificed. After sacrification, animals were subjected to necropsy. For repeated
      dose toxicity study, rats of either sex were orally administered with
      formulations at the dose of 300 mg/kg per day for a period of 28 days. The
      maximally tolerated dose of all formulations was found to be 2000 mg/kg. Repeated
      administration of formulations for 28 days did not show any significant changes
      in haematological and biochemical parameters in experimental animals. These
      results indicate that the formulations are safe, when tested in experimental
      animals.

PMID- 25754725
TI  - Efficient transposition of the youngest miniature inverted repeat transposable
      element family of yellow fever mosquito in yeast.
AB  - Miniature inverted repeat transposable elements (MITEs) are often the most
      numerous DNA transposons in plant and animal genomes. The dramatic amplification
      of MITE families during evolution is puzzling, because the transposase sources
      for the vast majority of MITE families are unknown. The yellow fever mosquito
      genome contains > 220-Mb MITE sequences; however, transposition activity has not
      been demonstrated for any of the MITE families. The Gnome elements are the
      youngest MITE family in this genome, with at least 116 identical copies. To test
      whether the putative autonomous element Ozma is capable of mobilizing Gnome and
      its two sibling MITEs, analyses were performed in a yeast transposition assay
      system. Whereas the wild-type transposase resulted in very low transposition
      activity, mutations in the region containing a putative nuclear export signal
      motif resulted in a dramatic (at least 4160-fold) increase in transposition
      frequency. We have also demonstrated that each residue of the novel DD37E motif
      is required for the activity of the Ozma transposase. Footprint sequences left at
      the donor sites suggest that the transposase may cleave between the second and
      the third nucleotides from the 5' ends of the elements. The excised elements
      reinsert specifically at dinucleotide 'TA', ~ 55% of them in yeast genes. The
      elements described in this article could potentially be useful as genetic tools
      for genetic manipulation of mosquitoes.

PMID- 25754726
TI  - Effects of Coculture With Immune Cells on the Developmental Competence of Mouse
      Preimplantation Embryos in Vitro and in Utero.
AB  - The aim of this study was to establish a coculture system using immune cells as
      well as an in vitro model for inflammatory conditioning using RAW 264.7 mouse
      macrophages activated by lipopolysaccharide. The direct and indirect coculture
      systems were applied to evaluate the influence of embryo-to-cell direct or
      indirect secretory molecules from the cocultured cells. Blastulation rate in
      vitro (94.6% vs 76.9%, P < .05) and implantation rate in utero (43.3% vs 17.6%, P
      < .01) were significantly increased in direct coculture with activated RAW 264.7
      cells compared to control. We also found the embryotrophic effects in vitro in
      the indirect coculture system. Our results indicate that coculture of mouse
      preimplantation embryos with immune cells could improve the developmental
      competence in vitro and in utero. Taken together, RAW 264.7 cells secret
      embryotrophic molecules, and it suggests the valuable insights that immune cells
      could improve in vitro culture conditions of preimplantation embryos. 

PMID- 25754727
TI  - Mapping of somatostatin-28 (1-12) in the alpaca (Lama pacos) brainstem.
AB  - Using an indirect immunoperoxidase technique, we studied the distribution of cell
      bodies and fibers containing somatostatin-28 (1-12) in the alpaca brainstem.
      Immunoreactive fibers were widely distributed throughout the whole brainstem: 34
      brainstem nuclei/regions showed a high or a moderate density of these fibers.
      Perikarya containing the peptide were widely distributed throughout the
      mesencephalon, pons and medulla oblongata. Cell bodies containing somatostatin-28
      (1-12) were observed in the lateral and medial divisions of the marginal nucleus
      of the brachium conjunctivum, reticular formation (mesencephalon, pons and
      medulla oblongata), inferior colliculus, periaqueductal gray, superior
      colliculus, pericentral division of the dorsal tegmental nucleus, interpeduncular
      nucleus, nucleus of the trapezoid body, vestibular nucleus, motor dorsal nucleus
      of the vagus, nucleus of the solitary tract, nucleus praepositus hypoglossi, and
      in the substantia nigra. This widespread distribution indicates that somatostatin
      28 (1-12) is involved in multiple physiological actions in the alpaca brainstem.

PMID- 25754728
TI  - Transurethral Holmium Laser Cystolithotripsy in Children: Single Center
      Experience.
AB  - PURPOSE: To evaluate prospectively safety and efficacy of transurethral
      cystolithotripsy (CL) in children using holmium:yttrium-aluminum-garnet (Ho:YAG)
      laser. This is important in developing countries, because the risk of bladder
      stones in children is high. Open cystolithotomy (OC) was the main line of
      treatment. A gradual shift has occurred toward endourologic treatment after
      improvement of pediatric endoscopes. PATIENTS AND METHODS: Between January 2010
      and May 2011, 33 children <12 years old with vesical calculi were treated.
      Children with orthopedic deformities, urethral stricture, history of urethral
      operations or bladder reconstruction, or stones >4 cm were excluded. Cystoscopies
      were performed under general anesthesia using 9 to 11F cystoscopes. Stones were
      completely fragmented under video guidance. Ho:YAG was applied at a power of 30
      W. RESULTS: Median age was 3 years (0.5-11). Mean stone size was 2.02+/-0.82 cm
      (1-4 cm). Mean operative duration was 31.21 minutes (20-50). All children were
      discharged within 24 hours. A single operative session was performed for each
      patient. No complications were detected. After a mean follow-up of 16.87+/-4.08
      months, all children were stone free, without development of any urethral
      stricture or recurrence of stones. Operative duration was significantly longer in
      stones >20 mm (P<0.001). CONCLUSION: Ho:YAG laser CL is a safe and successful
      minimally invasive treatment option for bladder stones in children. Success rate
      was 100% without development of any complications or recurrence.

PMID- 25754729
TI  - Genetic parameters for different growth scales in GIFT strain of Nile tilapia
      (Oreochromis niloticus).
AB  - Body weight, length, width and depth at two growth stages were observed for a
      total of 5015 individuals of GIFT strain, along with a pedigree including 5588
      individuals from 104 sires and 162 dams was collected. Multivariate animal models
      and a random regression model were used to genetically analyse absolute and
      relative growth scales of these growth traits. In absolute growth scale, the
      observed growth traits had moderate heritabilities ranging from 0.321 to 0.576,
      while pairwise ratios between body length, width and depth were lowly inherited
      and maximum heritability was only 0.146 for length/depth. All genetic
      correlations were above 0.5 between pairwise growth traits and genetic
      correlation between length/width and length/depth varied between both growth
      stages. Based on those estimates, selection index of multiple traits of interest
      can be formulated in future breeding program to improve genetically body weight
      and morphology of the GIFT strain. In relative growth scale, heritabilities in
      relative growths of body length, width and depth to body weight were 0.257, 0.412
      and 0.066, respectively, while genetic correlations among these allometry
      scalings were above 0.8. Genetic analysis for joint allometries of body weight to
      body length, width and depth will contribute to genetically regulate the growth
      rate between body shape and body weight. 

PMID- 25754730
TI  - Student-examiners in an OSCE: is it worth it?

PMID- 25754732
TI  - Base Excision Repair in the Mitochondria.
AB  - The 16.5 kb human mitochondrial genome encodes for 13 polypeptides, 22 tRNAs and
      2 rRNAs involved in oxidative phosphorylation. Mitochondrial DNA (mtDNA), unlike
      its nuclear counterpart, is not packaged into nucleosomes and is more prone to
      the adverse effects of reactive oxygen species (ROS) generated during oxidative
      phosphorylation. The past few decades have witnessed an increase in the number of
      proteins observed to translocate to the mitochondria for the purposes of
      mitochondrial genome maintenance. The mtDNA damage produced by ROS, if not
      properly repaired, leads to instability and can ultimately manifest in
      mitochondrial dysfunction and disease. The base excision repair (BER) pathway is
      employed for the removal and consequently the repair of deaminated, oxidized, and
      alkylated DNA bases. Specialized enzymes called DNA glycosylases, which locate
      and cleave the damaged base, catalyze the first step of this highly coordinated
      repair pathway. This review focuses on members of the four human BER DNA
      glycosylase superfamilies and their subcellular localization in the mitochondria
      and/or the nucleus, as well as summarizes their structural features, biochemical
      properties, and functional role in the excision of damaged bases.

PMID- 25754734
TI  - Editorial comment from Dr Silberstein to Three-dimensional printing in urological
      surgery: what are the possibilities?

PMID- 25754733
TI  - Expression of SOD and APX genes positively regulates secondary cell wall
      biosynthesis and promotes plant growth and yield in Arabidopsis under salt
      stress.
AB  - Abiotic stresses cause accumulation of reactive oxygen species (ROS), such as
      hydrogen peroxide (H2O2) in plants. Sophisticated mechanisms are required to
      maintain optimum level of H2O2 that acts as signalling molecule regulating
      adaptive response to salt stress. CuZn-superoxide dismutase (CuZn-SOD) and
      ascorbate peroxidase (APX) constitute first line of defence against oxidative
      stress. In the present study, PaSOD and RaAPX genes from Potentilla atrosanguinea
      and Rheum australe, respectively were overexpressed individually as well as in
      combination in Arabidopsis thaliana. Interestingly, PaSOD and dual transgenic
      lines exhibit enhanced lignin deposition in their vascular bundles with altered
      S:G ratio under salt stress. RNA-seq analysis revealed that expression of PaSOD
      gene in single and dual transgenics positively regulates expression of lignin
      biosynthesis genes and transcription factors (NACs, MYBs, C3Hs and WRKY), leading
      to enhanced and ectopic deposition of lignin in vascular tissues with larger
      xylem fibres and alters S:G ratio, as well. In addition, transgenic plants
      exhibit growth promotion, higher biomass production and increased yield under
      salt stress as compared to wild type plants. Our results suggest that in dual
      transgenics, ROS generated during salt stress gets converted into H2O2 by SOD and
      its optimum level was maintained by APX. This basal level of H2O2 acts as
      messenger for transcriptional activation of lignin biosynthesis in vascular
      tissue, which provides mechanical strength to plants. These findings reveal an
      important role of PaSOD and RaAPX in enhancing salt tolerance of transgenic
      Arabidopsis via increased accumulation of compatible solutes and by regulating
      lignin biosynthesis. 

PMID- 25754736
TI  - Acidosis increases MHC class II-restricted presentation of a protein endowed with
      a pH-dependent heparan sulfate-binding ability.
AB  - Heparan sulfate proteoglycans (HSPGs) are ubiquitously expressed molecules that
      participate in numerous biological processes. We previously showed that HSPGs
      expressed on the surface of APCs can serve as receptors for a hybrid protein
      containing an HS ligand and an Ag, which leads to more efficient stimulation of
      Th cells. To investigate whether such behavior is shared by proteins with
      inherent HS-binding ability, we looked for proteins endowed with this
      characteristic. We found that diphtheria toxin and its nontoxic mutant, called
      CRM197, can interact with HS. However, we observed that their binding ability is
      higher at pH 6 than at pH 7.4. Therefore, as extracellular acidosis occurs during
      infection by various micro-organisms, we assessed whether HS-binding capacity
      affects MHC class II-restricted presentation at different pHs. We first observed
      that pH decrease allows CRM197 binding to HSPG-expressing cells, including APCs.
      Then, we showed that this interaction enhances Ag uptake and presentation to Th
      cells. Lastly, we observed that pH decrease does not affect processing and
      presentation abilities of the APCs. Our findings show that acidic pH causes an
      HSPG-mediated uptake and an enhancement of T cell stimulation of Ags with the
      inherent ability to bind HSPGs pH-dependently. Furthermore, they suggest that
      proteins from micro-organisms with this binding characteristic might be supported
      more efficiently by the adaptive immune system when acidosis is triggered during
      infection. 

PMID- 25754735
TI  - Paliperidone and aripiprazole differentially affect the strength of calcium
      secretion coupling in female pituitary lactotrophs.
AB  - Hyperprolactinemia is a common adverse in vivo effect of antipsychotic
      medications that are used in the treatment of patients with schizophrenia. Here,
      we compared the effects of two atypical antipsychotics, paliperidone and
      aripiprazole, on cAMP/calcium signaling and prolactin release in female rat
      pituitary lactotrophs in vitro. Dopamine inhibited spontaneous cAMP/calcium
      signaling and prolactin release. In the presence of dopamine, paliperidone
      rescued cAMP/calcium signaling and prolactin release in a concentration-dependent
      manner, whereas aripiprazole was only partially effective. In the absence of
      dopamine, paliperidone stimulated cAMP/calcium signaling and prolactin release,
      whereas aripiprazole inhibited signaling and secretion more potently but less
      effectively than dopamine. Forskolin-stimulated cAMP production was facilitated
      by paliperidone and inhibited by aripiprazole, although the latter was not as
      effective as dopamine. None of the compounds affected prolactin transcript
      activity, intracellular prolactin accumulation, or growth hormone secretion.
      These data indicate that paliperidone has dual hyperprolactinemic actions in
      lactotrophs i) by preserving the coupling of spontaneous electrical activity and
      prolactin secretion in the presence of dopamine and ii) by inhibiting intrinsic
      dopamine receptor activity in the absence of dopamine, leading to enhanced
      calcium signaling and secretion. In contrast, aripiprazole acts on prolactin
      secretion by attenuating, but not abolishing, calcium-secretion coupling. 

PMID- 25754737
TI  - Anti-IL-17 therapy restricts and reverses late-term corneal allorejection.
AB  - Corneal allograft rejection has been described as a Th1-mediated process
      involving IFN-gamma production. However, recent evidence also implicated IL-17 as
      being involved in acute corneal allograft responses. Our data support that IL-17
      is involved in early acute corneal allograft acceptance. However, we decided to
      extend these studies to include a later phase of rejection in which there is a
      peak of IL-17 production that is >15-fold higher than that seen during acute
      rejection and occurs >45 d postengraftment at the onset of late-term rejection.
      We demonstrate that neutralizing IL-17A at this time significantly reduced
      corneal graft rejection. Surprisingly, when corneal grafts that are undergoing
      this later phase of rejection are treated with anti-IL-17A, there is a reversal
      of both opacity and neovascularization. Compared with the early phase of
      rejection, the cellular infiltrate is significantly less, with a greatly reduced
      presence of Gr-1(+) neutrophils and a relative increase in CD4(+) T cells and
      macrophages. We went on to identify that the cells expressing IL-17 were CD4(+)
      IL-17(+) T cells and, somewhat surprisingly, IL-17(+) F4/80(+) macrophages within
      the rejecting corneal allografts. Taken together, these findings describe a
      distinct late phase of corneal allograft rejection that is likely mediated by
      Th17 cells; therapeutic neutralization of IL-17A reverses this rejection. This
      further suggests that IL-17 might serve as an excellent therapeutic target to
      reduce this form of corneal allograft rejection. 

PMID- 25754738
TI  - Relative expression levels of the HLA class-I proteins in normal and HIV-infected
      cells.
AB  - The expression level of HLA class-I proteins is known to influence pathological
      outcomes: pathogens downregulate HLA to evade host immune responses, host
      inflammatory reactions upregulate HLA, and differences among people with regard
      to the steady-state expression levels of HLA associate with disease
      susceptibility. Yet precise quantification of relative expression levels of the
      various HLA loci is difficult because of the tremendous polymorphism of HLA. We
      report relative expression levels of HLA-A, HLA-B, HLA-C, and HLA-E proteins for
      the specific haplotype A*02:01, B*44:02, C*05:01, which were characterized using
      two independent methods based on flow cytometry and mass spectrometry. PBLs from
      normal donors showed that HLA-A and HLA-B proteins are expressed at similar
      levels, which are 13-18 times higher than HLA-C by flow cytometry and 4-5 times
      higher than HLA-C by mass spectrometry; these differences may reflect variation
      in the conformation or location of proteins detected. HLA-E was detected at a
      level 25 times lower than that of HLA-C by mass spectrometry. Primary CD4(+) T
      cells infected with HIV in vitro were also studied because HIV downregulates
      selective HLA types. HLA-A and HLA-B were reduced on HIV-infected cells by a
      magnitude that varied between cells in an infected culture. Averaging all
      infected cells from an individual showed HLA-A to be 1-3 times higher and HLA-B
      to be 2-5 times higher than HLA-C by flow cytometry. These results quantify
      substantial differences in expression levels of the proteins from different HLA
      loci, which are very likely physiologically significant on both uninfected and
      HIV-infected cells. 

PMID- 25754739
TI  - Mast cells play an important role in chlamydia pneumoniae lung infection by
      facilitating immune cell recruitment into the airway.
AB  - Mast cells are known as central players in allergy and anaphylaxis, and they play
      a pivotal role in host defense against certain pathogens. Chlamydia pneumoniae is
      an important human pathogen, but it is unclear what role mast cells play during
      C. pneumoniae infection. We infected C57BL/6 (wild-type [WT]) and mast cell
      deficient mice (Kit(W-sh/W-sh) [Wsh]) with C. pneumoniae. Wsh mice showed
      improved survival compared with WT mice, with fewer cells in Wsh bronchoalveolar
      lavage fluid (BALF), despite similar levels of cytokines and chemokines. We also
      found a more rapid clearance of bacteria from the lungs of Wsh mice compared with
      WT mice. Cromolyn, a mast cell stabilizer, reduced BALF cells and bacterial
      burden similar to the levels seen in Wsh mice; conversely, Compound 48/80, a mast
      cell degranulator, increased the number of BALF cells and bacterial burden.
      Histology showed that WT lungs had diffuse inflammation, whereas Wsh mice had
      patchy accumulations of neutrophils and perivascular accumulations of
      lymphocytes. Infected Wsh mice had reduced amounts of matrix metalloprotease-9 in
      BALF and were resistant to epithelial integral membrane protein degradation,
      suggesting that barrier integrity remains intact in Wsh mice. Mast cell
      reconstitution in Wsh mice led to enhanced bacterial growth and normal epithelial
      integral membrane protein degradation, highlighting the specific role of mast
      cells in this model. These data suggest that mast cells play a detrimental role
      during C. pneumoniae infection by facilitating immune cell infiltration into the
      airspace and providing a more favorable replicative environment for C.
      pneumoniae. 

PMID- 25754740
TI  - Importance of outer-sphere and aggregation phenomena in the relaxation properties
      of phosphonated gadolinium complexes with potential applications as MRI contrast
      agents.
AB  - A series composed of a tetra-, a tris- and a bisphosphonated ligand based on a
      pyridine scaffold (L(4) , L(3) and L(2) , respectively) was studied within the
      frame of lanthanide (Ln) coordination. The stability constants of the complexes
      formed with lanthanide cations (Ln=La, Nd, Eu, Gd, Tb, Er and Lu) were determined
      by potentiometry in aqueous solutions (25.0  degrees C, 0.1 M NaClO4 ), showing
      that the tetraphosphonated complexes are among the most stable Ln(III) complexes
      reported in the literature. The complexation of L(4) was further studied by
      different titration experiments using mass spectrometry and various spectroscopic
      techniques including UV/Vis absorption, and steady state and time-resolved
      luminescence (Ln=Eu and Tb). Titration experiments confirmed the formation of
      highly stable [LnL(4) ] complexes. (31) P NMR experiments of the LuL(4) complex
      revealed an intramolecular interconversion process which was studied at different
      temperatures and was rationalized by DFT modelling. The relaxivity properties of
      the Gd(III) complexes were studied by recording their (1) H NMRD profiles at
      various temperatures, by temperature dependent (17) O NMR experiments (GdL(4) )
      and by pH dependent relaxivity measurements at 0.47 T (GdL(3) and GdL(2) ). In
      addition to the high relaxivity values observed for all complexes, the results
      showed an important second-sphere contribution to relaxivity and pH dependent
      variations associated with the formation of aggregates for GdL(2) and GdL(3) .
      Finally, intravenous injection of GdL(4) to a mouse was followed by dynamic MRI
      imaging at 1.5 T, which showed that the complex can be immediately found in the
      blood stream and rapidly eliminated through the liver and in large part through
      the kidneys.

PMID- 25754741
TI  - Safety of vaccination against influenza A (H1N1) during pregnancy in the
      Netherlands: results on pregnancy outcomes and infant's health: cross-sectional
      linkage study.
AB  - OBJECTIVE: This study aims to assess the safety of Influenza A(H1N1), vaccination
      administered during the second and third trimester and containing MF59 and
      thiomersal (Focetria((r)) ), measured by pregnancy outcomes and infant's health.
      DESIGN: Cross-sectional linkage study. SETTING AND SAMPLE: A sample of pregnant
      women, eligible for prenatal screening, were invited to participate. METHODS:
      Questionnaire data were linked with the Netherlands Perinatal Registry (n =
      1920). Information on infant growth, development (n = 1739) and infection-related
      contacts with the general practitioner (GP) during the first year of life (n =
      1671) was obtained. MAIN OUTCOME MEASURES: Multivariate logistic regression was
      used to assess the association between H1N1 vaccination and small-for-gestational
      age infant, preterm delivery and a composite adverse outcome, i.e. low Apgar
      score, neonatal intensive care unit admission, neonatal resuscitation or
      perinatal death. Influence of maternal vaccination on growth, development and GP
      infection-related contact rates were assessed using multivariate linear mixed
      modelling and multivariate negative binomial regression, respectively. RESULTS:
      Response rate was 21%. Though we found differences in characteristics between
      unvaccinated and vaccinated women, in the multivariate analyses no association
      was found between H1N1 vaccination and small-for-gestational-age (odds ratio [OR]
      0.84; 95% confidence interval [95% CI] 0.50-1.43), preterm delivery (OR 0.98; 95%
      CI 0.59-1.62) and the composite adverse outcome (OR 0.84; 95% CI 0.44-1.60). We
      found no differences in weight-for-age (-0.05; 95% CI -0.13 to 0.04), length-for
      age (-0.01; 95% CI -0.09 to 0.06), head-circumference-for-age (-0.05; 95% CI 
      0.13 to 0.03), developmental scores (-0.06; 95% CI -0.28 to 0.17) and infection
      related GP contact rates (incidence rate ratio 1.07; 95% CI 0.91-1.28) between
      infants of unvaccinated and vaccinated mothers. CONCLUSION: Pregnancy outcomes
      did not differ between H1N1-vaccinated and unvaccinated women. Furthermore,
      growth, development and GP infection-related contact rates, assessed after the
      first year of life, were similar in offspring of vaccinated and unvaccinated
      mothers. TWEETABLE ABSTRACT: No increased risk for adverse pregnancy outcomes and
      infant's health following influenza vaccination.

PMID- 25754742
TI  - Risk factors for infection with carbapenem-resistant Klebsiella pneumoniae after
      liver transplantation: the importance of pre- and posttransplant colonization.
AB  - Improved understanding of risk factors associated with carbapenem-resistant
      Klebsiella pneumoniae (CR-KP) infection after liver transplantation (LT) can aid
      development of effective preventive strategies. We performed a prospective cohort
      study of all adult patients undergoing LT at our hospital during 30-month period
      to define risk factors associated with CR-KP infection. All patients were
      screened for CR-KP carriage by rectal swabs before and after LT. No therapy was
      administered to decolonize or treat asymptomatic CR-KP carriers. All patients
      were monitored up to 180 days after LT. Of 237 transplant patients screened, 41
      were identified as CR-KP carriers (11 at LT, 30 after LT), and 20 developed CR-KP
      infection (18 bloodstream-infection, 2 pneumonia) a median of 41.5 days after LT.
      CR-KP infection rates among patients non-colonized, colonized at LT, and
      colonized after LT were 2%, 18.2% and 46.7% (p < 0.001). Independent risk factors
      for CR-KP infection identified by multivariate analysis, included: renal
      replacement-therapy; mechanical ventilation > 48 h; HCV recurrence, and
      colonization at any time with CR-KP. Based on these four variables, we developed
      a risk score that effectively discriminated patients at low versus higher risk
      for CR-KP infection (AUC 0.93, 95% CI 0.86-1.00, p < 0.001). Our results may help
      to design preventive strategies for LT recipients in CR-KP endemic areas. 

PMID- 25754743
TI  - Activation of Nrf2/Keap1 signaling and autophagy induction against oxidative
      stress in heart in iron deficiency.
AB  - We investigated the effects of dietary iron deficiency on the redox system in the
      heart. Dietary iron deficiency increased heart weight and accumulation of
      carbonylated proteins. However, expression levels of heme oxygenase-1 and LC3-II,
      an antioxidant enzyme and an autophagic marker, respectively, in iron-deficient
      mice were upregulated compared to the control group, resulting in a surrogate
      phenomenon against oxidative stress.

PMID- 25754744
TI  - Oral mucosal lesions in older people: relation to salivary secretion, systemic
      diseases and medications.
AB  - OBJECTIVES: To determine the prevalence of oral mucosal lesions in a sample of
      older Danish people and to investigate their associations with age, gender,
      systemic diseases, medications, xerostomia and salivary secretion. METHODS: A
      total of 668 community-dwelling individuals aged 65-95 years underwent a clinical
      examination, measurements of unstimulated and stimulated whole and labial
      salivary flow rates and an interview regarding xerostomia, general health,
      medication, tobacco and alcohol habits. RESULTS: Seventy-five per cent of all
      participants and 70% of the non-medicated ones had one or more oral mucosal
      lesions. The most prevalent lesions were lingual varicosities (28.3%), denture
      stomatitis (12.7%), candidiasis (11.8%), fissured tongue (9.1%) and frictional
      keratosis (8.4%). Lesions were generally associated with smoking and xerostomia.
      Varicosities were more common in participants with systemic diseases and
      medication intake, particularly with cardiovascular diseases and agents. Fissured
      tongue and atrophic tongue were associated with female gender, xerostomia and low
      unstimulated whole and labial salivary secretion. Oral candidiasis was associated
      with older age; being male; current smoker; having >3 diseases, intake of
      medications and low salivary flow rates; and identified in relation to denture
      stomatitis, fissured tongue and atrophic tongue and median rhomboid glossitis.
      CONCLUSIONS: Oral mucosal lesions are prevalent in older Danish people and
      generally associated with changes in both local and systemic factors. Tongue
      lesions in particular appeared as indicators that may identify patients with
      specific need of oral intervention.

PMID- 25754745
TI  - Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE) for the
      diagnosis of dementia within a secondary care setting.
AB  - BACKGROUND: The diagnosis of dementia relies on the presence of new-onset
      cognitive impairment affecting an individual's functioning and activities of
      daily living. The Informant Questionnaire on Cognitive Decline in the Elderly
      (IQCODE) is a questionnaire instrument, completed by a suitable 'informant' who
      knows the patient well, designed to assess change in functional performance
      secondary to cognitive change; it is used as a tool to identifying those who may
      have dementia.In secondary care there are two specific instances where patients
      may be assessed for the presence of dementia. These are in the general acute
      hospital setting, where opportunistic screening may be undertaken, or in
      specialist memory services where individuals have been referred due to perceived
      cognitive problems. To ensure an instrument is suitable for diagnostic use in
      these settings, its test accuracy must be established. OBJECTIVES: To determine
      the diagnostic accuracy of the informant-based questionnaire IQCODE, for
      detection of all-cause (undifferentiated) dementia in adults presenting to
      secondary-care services. SEARCH METHODS: We searched the following sources on the
      28th of January 2013: ALOIS (Cochrane Dementia and Cognitive Improvement Group),
      MEDLINE (Ovid SP), EMBASE (Ovid SP), PsycINFO (Ovid SP), BIOSIS Previews (Thomson
      Reuters Web of Science), Web of Science Core Collection (includes Conference
      Proceedings Citation Index) (Thomson Reuters Web of Science), CINAHL (EBSCOhost)
      and LILACS (BIREME). We also searched sources specific to diagnostic test
      accuracy: MEDION (Universities of Maastricht and Leuven); DARE (Database of
      Abstracts of Reviews of Effects - via the Cochrane Library); HTA Database (Health
      Technology Assessment Database via the Cochrane Library) and ARIF (Birmingham
      University). We also checked reference lists of relevant studies and reviews,
      used searches of known relevant studies in PubMed to track related articles, and
      contacted research groups conducting work on IQCODE for dementia diagnosis to try
      to find additional studies. We developed a sensitive search strategy; search
      terms were designed to cover key concepts using several different approaches run
      in parallel and included terms relating to cognitive tests, cognitive screening
      and dementia. We used standardised database subject headings such as MeSH terms
      (in MEDLINE) and other standardised headings (controlled vocabulary) in other
      databases, as appropriate. SELECTION CRITERIA: We selected those studies
      performed in secondary-care settings, which included (not necessarily
      exclusively) IQCODE to assess for the presence of dementia and where dementia
      diagnosis was confirmed with clinical assessment. For the 'secondary care'
      setting we included all studies which assessed patients in hospital (e.g. acute
      unscheduled admissions, referrals to specialist geriatric assessment services
      etc.) and those referred for specialist 'memory' assessment, typically in
      psychogeriatric services. DATA COLLECTION AND ANALYSIS: We screened all titles
      generated by electronic database searches, and reviewed abstracts of all
      potentially relevant studies. Two independent assessors checked full papers for
      eligibility and extracted data. We determined quality assessment (risk of bias
      and applicability) using the QUADAS-2 tool, and reporting quality using the STARD
      tool. MAIN RESULTS: From 72 papers describing IQCODE test accuracy, we included
      13 papers, representing data from 2745 individuals (n = 1413 (51%) with
      dementia). Pooled analysis of all studies using data presented closest to a cut
      off of 3.3 indicated that sensitivity was 0.91 (95% CI 0.86 to 0.94); specificity
      0.66 (95% CI 0.56 to 0.75); the positive likelihood ratio was 2.7 (95% CI 2.0 to
      3.6) and the negative likelihood ratio was 0.14 (95% CI 0.09 to 0.22).There was a
      statistically significant difference in test accuracy between the general
      hospital setting and the specialist memory setting (P = 0.019), suggesting that
      IQCODE performs better in a 'general' setting.We found no significant differences
      in the test accuracy of the short (16-item) versus the 26-item IQCODE, or in the
      language of administration.There was significant heterogeneity in the included
      studies, including a highly varied prevalence of dementia (10.5% to 87.4%).
      Across the included papers there was substantial potential for bias, particularly
      around sampling of included participants and selection criteria, which may limit
      generalisability. There was also evidence of suboptimal reporting, particularly
      around disease severity and handling indeterminate results, which are important
      if considering use in clinical practice. AUTHORS' CONCLUSIONS: The IQCODE can be
      used to identify older adults in the general hospital setting who are at risk of
      dementia and require specialist assessment; it is useful specifically for ruling
      out those without evidence of cognitive decline. The language of administration
      did not affect test accuracy, which supports the cross-cultural use of the tool.
      These findings are qualified by the significant heterogeneity, the potential for
      bias and suboptimal reporting found in the included studies.

PMID- 25754746
TI  - Olive oil DNA fingerprinting by multiplex SNP genotyping on fluorescent
      microspheres.
AB  - Olive oil cultivar verification is of primary importance for the competitiveness
      of the product and the protection of consumers and producers from fraudulence.
      Single-nucleotide polymorphisms (SNPs) have emerged as excellent DNA markers for
      authenticity testing. This paper reports the first multiplex SNP genotyping assay
      for olive oil cultivar identification that is performed on a suspension of
      fluorescence-encoded microspheres. Up to 100 sets of microspheres, with unique
      "fluorescence signatures", are available. Allele discrimination was accomplished
      by primer extension reaction. The reaction products were captured via
      hybridization on the microspheres and analyzed, within seconds, by a flow
      cytometer. The "fluorescence signature" of each microsphere is assigned to a
      specific allele, whereas the signal from a reporter fluorophore denotes the
      presence of the allele. As a model, a panel of three SNPs was chosen that enabled
      identification of five common Greek olive cultivars (Adramytini, Chondrolia
      Chalkidikis, Kalamon, Koroneiki, and Valanolia).

PMID- 25754747
TI  - Intravenous iron sucrose for children with iron deficiency anemia: a single
      institution study.
AB  - BACKGROUND: Intravenous iron sucrose is not recommended by its manufacturers for
      use in children despite extensive safety and efficacy data in adults. METHODS: We
      reviewed the experience of our department between January, 2011 and February,
      2014 with the use of intravenous iron sucrose in children <=14 years of age who
      failed in oral iron therapy for iron deficiency anemia (IDA). RESULTS: Twelve
      children (6 females) aged 1.2-14 years (median age 8.9 years) received at least
      one dose of intravenous iron sucrose. Ten patients had IDA inadequately treated
      or non-responsive to oral iron therapy. One patient received therapy for blood
      transfusion avoidance and one for presumed iron refractory iron deficiency anemia
      (IRIDA). Iron sucrose infusions were given on alternate days up to three times
      per week. The number of infusions per patient ranged from 2 to 6 (median, 3), the
      individual doses from 100 mg to 200 mg (median, 200 mg), and the total doses from
      200 mg to 1200 mg (median, 400 mg). Iron sucrose was effective in raising the
      hemoglobin concentration to normal in all patients with IDA, i.e., from 7.6+/
      2.38 g/dL to 12.4+/-0.64 g/dL, within 31-42 days after the first infusion. The
      single patient with IRIDA demonstrated a 1.8 g/dL rise. Injection site disorders
      in three cases and transient taste perversion in one case were the only side
      effects. CONCLUSION: Intravenous iron sucrose appears to be safe and very
      effective in children with IDA who do not respond or cannot tolerate oral iron
      therapy.

PMID- 25754748
TI  - Intrapulmonary lipoma: a case report and literature review.
AB  - BACKGROUND: Intrapulmonary lipoma is extemely rare in children. So far, all
      reported pulmonary lipomas were from adult patients. METHODS: We present herein a
      case of intrapulmonary lipoma in a child and a review of the related literature.
      RESULTS: A 13-month-old boy was hospitalized because of cough and fever. Chest CT
      showed patchy infiltration and round-shape, hypodense homogeneous lesions located
      in the lung. After 19 days of antibiotic treatment, his clinic symptoms
      disappeared, but the round lesions remained without any change. One month and one
      year later, he was examined by chest MRI with technique of fat suppression. The
      child was diagnosed as having an intrapulmonary lipoma without biopsy.
      CONCLUSIONS: Intrapulmonary lipoma is rare in children. Chest CT and MRI are very
      important for the correct diagnosis of intrapulmonary lipoma.

PMID- 25754749
TI  - Feeding methods, sleep arrangement, and infant sleep patterns: a Chinese
      population-based study.
AB  - BACKGROUND: Findings from prior research into the effect of feeding methods on
      infant sleep are inconsistent. The objectives of this study were to examine
      infants' sleep patterns by feeding methods and sleep arrangement from birth to
      eight months old. METHODS: This longitudinal cohort study enrolled 524 pregnant
      women at 34-41 weeks of gestation and their infants after delivery in 2006 and
      followed up until eight months postpartum. The study subjects were recruited from
      nine women and children hospitals in nine cities in China (Beijing, Chongqing,
      Wuhan, Changsha, Nanning, Xiamen, Xi'an, Jinan, and Hailin). Participating
      infants were followed up weekly during the first month and monthly from the
      second to the eighth month after birth. Twenty-four hour sleep diaries recording
      infants' sleeping and feeding methods were administered based on caregiver's self
      report. Multivariable mixed growth curve models were fitted to estimate the
      effects of feeding methods and sleep arrangement on infants' sleep patterns over
      time, controlling for maternal and paternal age, maternal and paternal education
      level, household income, supplementation of complementary food, and infant birth
      weight and length. RESULTS: Exclusively formula fed infants had the greatest
      sleep percentage/24 h, followed by exclusively breast milk fed infants and
      partially breast milk fed infants (P<0.01). Night waking followed a similar
      pattern. However, the differences in sleep percentage and night waking frequency
      between exclusively formula and exclusively breast milk fed infants weakened over
      time as infants developed. In addition, compared to infants with bed-sharing
      sleep arrangement, those with room sharing sleep arrangement had greater daytime
      and 24-hour infant sleep percentage, whereas those with sleeping alone sleep
      arrangement had greater nighttime sleep percentage. CONCLUSIONS: Our data based
      on caregiver's self-report suggested that partial breastfeeding and bed-sharing
      may be associated with less sleep in infants. Health care professionals need to
      work with parents of newborns to develop coping strategies that will help prevent
      early weaning of breastfeeding.

PMID- 25754750
TI  - Mizoribine in the treatment of pediatric-onset glomerular disease.
AB  - BACKGROUND: Mizoribine (MZR) is a selective inhibitor of inosine monophosphate
      dehydrogenase, a key enzyme in the pathway responsible for de novo synthesis of
      guanine nucleotides. As an immunosuppressant, MZR has been used successfully
      without any serious adverse effects in the treatment of renal diseases in
      children as well as adults. Besides its immunosuppressive effect, MZR has been
      reported to ameliorate tubulointerstitial fibrosis in rats via suppression of
      macrophage infiltration. DATA SOURCES: In this review, we summarize reported
      possible benefits of MZR in the treatment of pediatriconset glomerular disease.
      RESULTS: We recently observed that MZR itself selectively attenuates the
      expression of monocyte chemoattractant protein-1 at both the mRNA and protein
      levels in human mesangial cells. Since MZR binds specifically to 14-3-3 proteins
      and heat shock protein 60, both of which are reportedly expressed in inflamed
      glomeruli, MZR may bind directly to inflamed glomerular cells, thereby possibly
      preventing progressive damage from glomerulonephritis through a suppressive
      effect on activated macrophages and intrinsic renal cells. Moreover, it has
      recently been reported that MZR directly prevents podocyte injury through
      correction of the intracellular energy balance and nephrin biogenesis in cultured
      podocyte and rat models, suggesting a direct anti-proteinuric effect of MZR.
      CONCLUSIONS: These beneficial mechanisms of action of MZR as well as its
      immunosuppressive effect would warrant its use in the treatment of pediatric
      onset glomerular disease. Although further studies remain to be done, we believe
      that MZR may be an attractive treatment of choice for children with glomerular
      diseases from a histologic as well as clinical standpoint.

PMID- 25754751
TI  - Violence-related behaviors among adolescents and its association with cognitive
      emotion regulation strategies.
AB  - BACKGROUND: Adolescent violence is now regarded as a major public health concern.
      Despite growing interest in psychographic risk factors for violent behavior, few
      studies have explored the role of strategies to regulate cognitive emotion in
      adolescents. This study aimed to investigate the prevalence of adolescent
      violence behaviors and to identify the relationship between specific strategies
      to regulate cognitive emotion and forms of violent behavior.Adolescent violence
      is now regarded as a major public health concern. Despite growing interest in
      psychographic risk factors for violent behavior, few studies have explored the
      role of strategies to regulate cognitive emotion in adolescents. This study aimed
      to investigate the prevalence of adolescent violence behaviors and to identify
      the relationship between specific strategies to regulate cognitive emotion and
      forms of violent behavior. METHODS: We cross-sectionally surveyed 3315 students
      in grades 7 to 10 using anonymous, self-reporting questionnaires to examine
      strategies to regulate cognitive emotion and violence-related behaviors in young
      adolescents. A logistic regression model was used to identify the relationship
      between specific violent behaviors and strategies to regulate cognitive emotion.
      RESULTS: The most commonly reported type of violent behavior was verbal attack
      (48.6%), while 7.1% of students were involved in fights and 2.4% had been injured
      in fights. Boys were involved in all forms of violent behavior studied, and did
      so significantly more often than girls (P<0.05). Logistic regression revealed
      that six cognitive emotion strategies (self-blame, rumination, planning,
      reappraisal, catastrophisizing, and blaming others) were associated with violent
      behaviors, of which catastrophisizing was the most significant factor of all
      violent behaviors examined that were influenced by this strategy. CONCLUSIONS:
      Violence-related behaviors, especially verbal attacks, were common among
      adolescents. Several cognitive emotion regulation strategies were positively
      associated with specific violent behaviors, but catastrophisizing was strongly
      related to all forms of violent behavior. Thus, programs targeting adolescent
      violence must address this and other maladaptive cognitive emotion regulation
      strategies.

PMID- 25754752
TI  - Benign penile skin anomalies in children: a primer for pediatricians.
AB  - BACKGROUND: Abnormalities involving the skin coverage of the penis are difficult
      to define, but they can significantly alter penile appearance, and be a cause of
      parental concern. DATA SOURCES: The present review was based on a nonsystematic
      search of the English language medical literature using a combination of key
      words including "penile skin anomalies" and the specific names of the different
      conditions. RESULTS: Conditions were addressed in the following order, those
      mainly affecting the prepuce (phimosis, balanitis xerotica obliterans, balanitis,
      paraphimosis), those which alter penile configuration (inconspicuous penis and
      penile torsion), and lastly focal lesions (cysts, nevi and vascular lesions).
      Most of these anomalies are congenital, have no or minimal influence on urinary
      function, and can be detected on clinical examination. Spontaneous improvement is
      possible. In the majority of cases undergoing surgery, the potential
      psychological implications of genital malformation on patient development are the
      main reason for treatment, and the age generally recommended for surgery is after
      12 months of age. CONCLUSION: This review provides the pediatrician with a handy
      tool to identify the most common penile skin anomalies, counsel parents
      adequately, make sensible and evidence based choices for management, and
      recognize complications or untoward outcomes in patients undergoing surgery.

PMID- 25754753
TI  - Molecular pathophysiology of Bartter's and Gitelman's syndromes.
AB  - BACKGROUND: In the last two decades, progress in cytogenetic and genome research
      has enabled investigators to unravel the underlying molecular mechanisms of
      inherited tubulopathies such as Bartter's and Gitelman's syndromes and helped
      physicians to better understand not only these two pathologic entities but also
      renal pathophysiology and salt sensitive hypertension. DATA SOURCES: Articles
      collected from PubMed and open access journals included original articles,
      research articles, and comprehensive reviews. They were evaluated by the authors
      with an special emphasis on originality and up to date information about
      molecular pathophysiology. RESULTS: Bartter's and Gitelman's syndromes are two
      different inherited salt loosing tubulopathies. They are characterized by various
      inability of distal nephron to reabsorb sodium chloride with resultant
      extarcellular volume contraction and increased activity of the renin angiotensin
      aldosterone system. Hypokalemic metabolic alkalosis is a common feature of these
      two forms of tubulopathies. Hypercalciuria characterizes the majority of
      Bartter's syndrome, and hypomagnesemia with hypocalciuria characterizes
      Gitelman's syndrome. Low blood pressure is a common feature among patients who
      suffered from these tubulopathies. Bartter's syndromes encompass a heterogeneous
      group of ion channels defects localized at the thick ascending limp of Henle's
      loop with resultant loss of function of sodium-potassium-2 chloride
      cotransporter. These defects result in the impairment of the countercurrent
      multiplication system of the kidney as well as calcium, potassium and acid base
      disturbances which in the majority of cases are proved lethal especially in the
      antenatal and/or immediate postnatal life period. The underlying pathology in
      Gitelman's syndrome is defined to the distal convoluted tubule and is related to
      loss of function of the sodium-chloride cotransporter. The results of this defect
      encompass the inability of extracellular volume homeostasis, magnesium and
      potassium conservation, and acid base disturbances which are generally mild and
      in the majority of cases are not life-threatening. CONCLUSIONS: Recent advances
      in molecular pathophysiology of Bartter's and Gitelman's syndromes have helped
      physicians to better understand the underlying mechanisms of these pathologic
      entities which remain obscure. Data collected from experiments among genetically
      manipulated animals enable us to better understand the pathophysiology of
      mammalian kidney and the underlying mechanisms of salt sensitive hypertension and
      to lay a foundation for the future development of new drugs, especially diuretics
      and antihypertensive drugs.

PMID- 25754754
TI  - Newborn screening for galactosemia: a 30-year single center experience.
AB  - BACKGROUND: Galactosemia due to complete or near-complete galactose-1-phosphate
      uridyltransferase (GALT) deficiency was the first disorder added to the
      pioneering newborn screening panel besides phenylketonuria. In the last 50 years,
      many criticisms have been focused on the opportunity of its inclusion.
      Consequently, long-term single center experiences with this issue are generally
      lacking. METHODS: We reviewed the outcome of newborn screening for
      hypergalactosemia performed at our department since 1982 and the correspondent
      long-term clinical outcome. RESULTS: Among 1 123 909 newborns screened for
      hypergalactosemia, 33 showed abnormal results confirmed at second tier test.
      Thirteen patients were affected with classic galactosemia, 8 partial GALT
      deficiency, 3 severe galactokinase deficiency, 7 transient galactosemia, one
      congenital porto-systemic shunt, and one glucose transporter 2 deficiency. Acute
      neonatal liver failure in the late first week of life (5.8+/-1.1 days)
      unavoidably complicated the clinical course of classic galactosemia, unless in
      three second-born siblings treated on the basis of presumptive diagnosis
      immediately after newborn screening sample collection on day 3. Despite early
      treatment and long-term steadily normal peripheral blood galactose, 77% of
      patients with severe GALT deficiency present mild to severe intellectual
      disabilities. All patients with partial GALT deficiency showed normal
      intellectual development on a regular diet, as well as patients with
      galactokinase deficiency under treatment. CONCLUSIONS: Availability of screening
      results within the fifth day after birth would allow the prevention of acute
      decompensation in classic galactosemia. A systematic diagnostic work-up in all
      positive newborns is essential to unravel the etiology of hypergalactosemia.

PMID- 25754755
TI  - Effect of etanercept on refractory systemic-onset juvenile idiopathic arthritis.
AB  - BACKGROUND: Treatment of systemic-onset juvenile idiopathic arthritis (So-JIA) is
      challenging, and the efficacy of injectable recombinant human tumor necrosis
      factor type 1 receptor-antibody fusion protein (etanercept) on So-JIA has been
      controversial. METHODS: We retrospectively studied 12 patients with refractory
      systemic juvenile arthritis treated with etanercept at our hospital in the past 5
      years. The 12 patients were divided into a corticosteroid-dependent group (n=7)
      and an ineffective group (n=5) on the basis of their responses to treatment
      before the administration of etanercept. Etanercept was added to the treatment
      without substantially changing the original regimens in general, and doses, and
      signs of efficacy including alleviation or resolution of symptoms such as high
      fever, inflammatory arthropathy, eruption rash, hydrohymenitis, as well as
      changes in the levels of laboratory inflammatory markers such as the white blood
      cell count, erythrocyte sedimentation rate, levels of C-reactive protein and
      serum ferritin were recorded. RESULTS: Etanercept was withdrawn after the first
      dose from one patient in the corticosteroid-dependent group because of a systemic
      allergic rash, and was also withdrawn from one patient in the ineffective group
      after 2 months of treatment owing to inefficacy; the remaining 10 patients
      completed the entire treatment protocol, at which point etanercept was
      discontinued. At that time, clinical symptoms and laboratory inflammatory markers
      of the remaining patients were within the normal range and the mean dose of
      prednisone was 0.18 mg/kg per day, an 81% decrease from the mean dose at
      baseline. At present, the corticosteroid has been discontinued and only
      methotrexate maintenance treatment is used in 3 patients; the other 7 patients
      are treated with prednisone and methotrexate maintenance therapy. All of the 10
      patients are in a medicated remission with no recurrence. CONCLUSIONS: In the
      treatment of patients with refractory So-JIA, the principles of individual
      therapy and combinations of drugs should be followed. Etanercept is an important
      and valid candidate for use in such combined treatment strategies.

PMID- 25754756
TI  - Functional Impairment Is a Risk Factor for Knee Replacement in the Multicenter
      Osteoarthritis Study.
AB  - BACKGROUND: Debilitating pain associated with knee osteoarthritis (OA) often
      leads patients to seek and complete total knee arthroplasty (TKA). To date, few
      studies have evaluated the relation of functional impairment to the risk of TKA,
      despite the fact that OA is associated with functional impairment.
      QUESTIONS/PURPOSES: The purpose of our study was to (1) evaluate whether function
      as measured by WOMAC physical function subscale was associated with undergoing
      TKA; and (2) whether any such association varied by sex. METHODS: The National
      Institutes of Health-funded Multicenter Osteoarthritis Study (MOST) is an
      observational cohort study of persons aged 50 to 79 years with or at high risk of
      symptomatic knee OA who were recruited from the community. All eligible subjects
      with complete data were included in this analysis. Our study population sample
      consisted of 2946 patients with 5796 knees; 1776 (60%) of patients were women. We
      performed a repeated-measures analysis using baseline WOMAC physical function
      score to predict the risk of TKA from baseline to 30 months and WOMAC score at 30
      months to predict risk of incident TKA from 30 months to 60 months. We used
      generalized estimating equations to account for the correlation between two knees
      within an individual and across the two periods. We calculated relative risk (RR)
      of TKA over 30 months by WOMAC function using a score of 0 to 5 as the referent
      in multiple binomial regressions with log link. RESULTS: Those with the greatest
      functional impairment (WOMAC scores 40-68; 62 TKAs in 462 knee periods) had 15.5
      times (95% confidence interval [CI], 7.6-31.8; p<0.001) the risk of undergoing
      TKA over 30 months compared with the referent group (12 TKAs in 3604 knee
      periods), adjusting for basic covariates, and 5.9 times (95% CI, 2.8-12.5;
      p<0.001) the risk after further adjusting for knee pain severity. At every level
      of functional limitation, the RR for TKA for women was higher than for men, but
      interaction with sex did not reach significance after adjustment for covariates
      including ipsilateral pain (p=0.138). CONCLUSIONS: Baseline physical function
      appears to be an important element in patients considering TKA. Future studies
      should examine whether interventions to improve function can reduce the need for
      TKA. LEVEL OF EVIDENCE: Level III, observational cohort study.

PMID- 25754757
TI  - Percutaneous Distraction Pinning for Metacarpophalangeal Joint Stabilization
      After Blast or Crush Injuries of the Hand.
AB  - BACKGROUND: Unstable, severely comminuted fractures of the metacarpophalangeal
      (MCP) joint are difficult to treat. Closed treatment and casting of these
      fractures often fail to maintain proper alignment and impede wound care where
      concomitant open injuries such as gunshot wounds are present. Conventional
      pinning or plating techniques are not feasible if extensive bone loss and
      comminution are present. A distraction pinning technique represents a potential
      alternative, but results with this approach, to our knowledge, have not been
      reported. QUESTIONS/PURPOSES: The purposes of this study were (1) to evaluate the
      effectiveness (defined as osseous union and joint stability) of distraction
      pinning for comminuted fractures involving MCP joints after gunshot or crush
      injuries; (2) to report the short-term results in terms of pain and function in a
      small group of patients who underwent MCP distraction pinning; and (3) to
      evaluate complications and return to work status of these patients in the short
      term. METHODS: We reviewed 10 patients with comminuted pilon-type fractures of
      the base of the proximal phalanx or metacarpal head treated with wire distraction
      fixation from 2005 and 2014. During that period, we used this technique to treat
      all patients whose fractures were deemed too comminuted for plating or pinning,
      and during that period, no other techniques (such as simple external fixation)
      were used for patients meeting those indications. The minimum followup was 6
      months; eight of the 10 patients were accounted at a median of 10 months (range,
      6-89 months). The median age was 47 years (range, 28-57 years), and seven of the
      eight were male. Kirschner wire fixation frames were removed 3.5 to 6 weeks after
      the index surgery when fracture consolidation was confirmed on radiography by the
      treating surgeon. Stability and range of motion of the MCP joint were assessed
      using physical examination, radiographs, and goniometer by the treating surgeon.
      Patients completed the Quick Disabilities of the Arm, Shoulder and Hand score at
      latest followup or by telephone, and complications were assessed by chart review.
      RESULTS: All fractures were healed with stable MCP joints. Eight patients
      reported having no pain or minimal pain of their injuries to the hand. The median
      finger and thumb MCP arc of motion were 80 degrees  (range, 70 degrees -105
      degrees ) and 30 degrees  (range, 0 degrees -60 degrees ), respectively. The
      median Quick Disabilities of the Arm, Shoulder and Hand score was 3 (range, 0
      41). One patient underwent a second surgical procedure for bone grafting and soft
      tissue coverage. Three patients developed pin site irritations and were treated
      with oral antibiotics. Six patients returned to their original job. CONCLUSIONS:
      The distraction pinning technique provides reliable osseous union and joint
      stability of comminuted pilon-type fractures of the base of the proximal phalanx
      or metacarpal head, even with associated open wounds. Future studies will need to
      evaluate these patients at longer term followup and compare this approach with
      other available techniques, because arthrosis, stiffness, and progressive loss of
      function seem likely to occur given the severity of these injuries. LEVEL OF
      EVIDENCE: Level IV, therapeutic study.

PMID- 25754759
TI  - CORR Insights((r)): Preoperative Opioid Misuse is Associated With Increased
      Morbidity and Mortality After Elective Orthopaedic Surgery.

PMID- 25754758
TI  - Early Characterization of Blast-related Heterotopic Ossification in a Rat Model.
AB  - BACKGROUND: Heterotopic ossification (HO) affects the majority of combat-related
      lower extremity wounds involving severe fracture and amputation. Defining the
      timing of early osteogenic-related genes may help identify candidate prophylactic
      agents and guide the timing of prophylactic therapy after blast and other combat
      related extremity injuries. QUESTIONS/PURPOSES: Using a recently developed animal
      model of combat-related HO, we sought to determine (1) the timing of early
      chondrogenesis, cartilage formation, and radiographic ectopic bone development;
      and (2) the early cartilage and bone-related gene and protein patterns in
      traumatized soft tissue. METHODS: We used an established rat HO model consisting
      of blast exposure, controlled femur fracture, crush injury, and transfemoral
      amputation through the zone of injury. Postoperatively, rats were euthanized on
      Days 3 to 28. We assessed evidence of early ectopic bone formation by micro-CT
      and histology and performed proteomic and gene expression analysis. RESULTS: All
      rats showed radiographic evidence of HO within 28 days. Key chondrogenic
      (collagen type I alpha 1 [COL1alpha1], p = 0.016) and osteogenic-related genes
      (Runt-related transcription factor 2 [RUNX-2], p = 0.029; osteoclacin [OCN], p =
      0.032; phosphate-regulating neutral endopeptidase, X-linked [PHEX], p = 0.0290,
      and POU domain class 5 transcription factor [POU5F], p = 0.016) and proteins
      (Noggin [NOG], p = 0.04, OCN, p = 0.02, RUNX- 2, p = 0.04, and substance P-1 [SP
      1], p = 0.01) in the injured soft tissue, normalized to the contralateral limb
      and/or sham-treated naive rats, increased on Days 3 to 14 postinjury. By 14 days,
      foci of hypertrophic chondrocytes, hyaline cartilage, and woven bone were present
      in the soft tissue surrounding the amputation site. CONCLUSIONS: We found that
      genes that regulate early chondrogenic and osteogenic signaling and bone
      development (COL1alpha1, RUNX-2, OCN, PHEX, and POU5F1) are induced early during
      the tissue reparative/healing phase in a rat model simulating a combat-related
      extremity injury. CLINICAL RELEVANCE: The ability to correlate molecular events
      with histologic and morphologic changes will assist researchers and clinicians to
      understand HO and hence formulate therapeutic interventions.

PMID- 25754760
TI  - Involvement of Endogenous Enkephalins and beta-Endorphin in Feeding and Diet
      Induced Obesity.
AB  - Studies implicate opioid transmission in hedonic and metabolic control of
      feeding, although roles for specific endogenous opioid peptides have barely been
      addressed. Here, we studied palatable liquid consumption in proenkephalin
      knockout (PENK KO) and beta-endorphin-deficient (BEND KO) mice, and how the body
      weight of these mice changed during consumption of an energy-dense highly
      palatable 'cafeteria diet'. When given access to sucrose solution, PENK KOs
      exhibited fewer bouts of licking than wild types, even though the length of bouts
      was similar to that of wild types, a pattern that suggests diminished food
      motivation. Conversely, BEND KOs did not differ from wild types in the number of
      licking bouts, even though these bouts were shorter in length, suggesting that
      they experienced the sucrose as being less palatable. In addition, licking
      responses in BEND, but not PENK, KO mice were insensitive to shifts in sucrose
      concentration or hunger. PENK, but not BEND, KOs exhibited lower baseline body
      weights compared with wild types on chow diet and attenuated weight gain when fed
      cafeteria diet. Based on this and related findings, we suggest endogenous
      enkephalins primarily set a background motivational tone regulating feeding
      behavior, whereas beta-endorphin underlies orosensory reward in high need states
      or when the stimulus is especially valuable. Overall, these studies emphasize
      complex interplays between endogenous opioid peptides targeting MU-receptors,
      such as enkephalins and endorphins, underlying the regulation of feeding and body
      weight that might explain the poor efficacy of drugs that generally target MU
      opioid receptors in the long-term control of appetite and body weight. 

PMID- 25754761
TI  - GABAB Receptor Agonist R-Baclofen Reverses Social Deficits and Reduces Repetitive
      Behavior in Two Mouse Models of Autism.
AB  - Autism spectrum disorder (ASD) is diagnosed by two core behavioral criteria,
      unusual reciprocal social interactions and communication, and stereotyped,
      repetitive behaviors with restricted interests. Excitatory/inhibitory imbalance
      is a prominent hypothesis for the etiology of autism. The selective GABAB
      receptor agonist R-baclofen previously reversed social deficits and reduced
      repetitive behaviors in a mouse model of Fragile X syndrome, and Arbaclofen
      improved some clinical symptoms in some Fragile X and ASD patients. To evaluate R
      baclofen in a broader range of mouse models of ASD, we tested both the R-baclofen
      enantiomer and the less potent S-baclofen enantiomer in two inbred strains of
      mice that display low sociability and/or high repetitive or stereotyped
      behaviors. R-baclofen treatment reversed social approach deficits in BTBR T+
      Itpr3tf/J (BTBR), reduced repetitive self-grooming and high marble burying scores
      in BTBR, and reduced stereotyped jumping in C58/J (C58), at nonsedating doses. S
      baclofen produced minimal effects at the same doses. These findings encourage
      investigations of R-baclofen in other preclinical model systems. Additional
      clinical studies may be warranted to further evaluate the hypothesis that the
      GABAB receptor represents a promising pharmacological target for treating
      appropriately stratified subsets of individuals with ASD. 

PMID- 25754763
TI  - Using Rasch analysis to identify midwifery students' learning about providing
      breastfeeding support.
AB  - AIM: To report on a study measuring midwifery students' self-reported abilities
      in teaching and supervising breastfeeding mothers. Abilities were assessed at two
      time intervals, before and after completing a maternal and infant nutrition topic
      with simultaneous clinical opportunities to consolidate their skills. METHOD: A
      convenience sample of midwifery students in an Australian university completed a
      pre- and post-intervention survey to assess their self-rated ability to teach and
      supervise breastfeeding mothers. Rasch analysis was used to gain conjoint
      estimates of students' self-reported abilities to teach and supervise
      breastfeeding mothers across 37 items with varying complexity of care needs.
      Rasch analysis was used to determine validity and reliability of the 37-item
      tool, to develop a hierarchical linear scale reflecting difficulty of
      breastfeeding supportive activities, and to determine student learning between
      the two time points. RESULTS: From 95 responses, 34 of the 37 items met the
      requirement for unidimensionality. Outcomes identified that midwifery students'
      self-efficacy measures for breastfeeding support abilities can be reliably
      estimated. A hierarchical scale for learning these clinical skills has been
      generated to inform curricula development and learning processes. While there was
      an overall increase in the ease of difficulty of 21 items in the survey at time
      point two, eight items were identified as becoming more difficult. CONCLUSION:
      The findings of this study challenge midwifery educators to reconsider the
      educational activities provided for midwifery students' that aim to develop the
      requisite skills to provide effective breastfeeding support, including the
      provision of specific clinical opportunities to learn from breastfeeding women.

PMID- 25754762
TI  - Effects of Fatty Acid Amide Hydrolase (FAAH) Inhibitors in Non-Human Primate
      Models of Nicotine Reward and Relapse.
AB  - Inhibition of the enzyme fatty acid amide hydrolase (FAAH) counteracts reward
      related effects of nicotine in rats, but it has not been tested for this purpose
      in non-human primates. Therefore, we studied the effects of the first- and second
      generation O-arylcarbamate-based FAAH inhibitors, URB597 (cyclohexyl carbamic
      acid 3'-carbamoyl-3-yl ester) and URB694 (6-hydroxy-[1,1'-biphenyl]-3-yl
      cyclohexylcarbamate), in squirrel monkeys. Both FAAH inhibitors: (1) blocked FAAH
      activity in brain and liver, increasing levels of endogenous ligands for
      cannabinoid and alpha-type peroxisome proliferator-activated (PPAR-alpha)
      receptors; (2) shifted nicotine self-administration dose-response functions in a
      manner consistent with reduced nicotine reward; (3) blocked reinstatement of
      nicotine seeking induced by reexposure to either nicotine priming or nicotine
      associated cues; and (4) had no effect on cocaine or food self-administration.
      The effects of FAAH inhibition on nicotine self-administration and nicotine
      priming-induced reinstatement were reversed by the PPAR-alpha antagonist, MK886.
      Unlike URB597, which was not self-administered by monkeys in an earlier study,
      URB694 was self-administered at a moderate rate. URB694 self-administration was
      blocked by pretreatment with an antagonist for either PPAR-alpha (MK886) or
      cannabinoid CB1 receptors (rimonabant). In additional experiments in rats, URB694
      was devoid of THC-like or nicotine-like interoceptive effects under drug
      discrimination procedures, and neither of the FAAH inhibitors induced dopamine
      release in the nucleus accumbens shell--consistent with their lack of robust
      reinforcing effects in monkeys. Overall, both URB597 and URB694 show promise for
      the initialization and maintenance of smoking cessation because of their ability
      to block the rewarding effects of nicotine and prevent nicotine priming-induced
      and cue-induced reinstatement.

PMID- 25754764
TI  - Microbial bioconversion and processing methods enhance the phenolic acid and
      flavonoids and the radical scavenging capacity of Smilax china L. leaf.
AB  - BACKGROUND: It has been reported that Smilax china L. leaf (SCL) provided various
      biological functions owing to polyphenols. The objective of the current study was
      to assess the enhancing effect of processing methods and microbial conversions on
      phenolic acid and flavonoid content and radical scavenging capacity of SCL for
      potential applications of diverse food products. RESULTS: Targeted phenolic acid
      (chlorogenic acid) and flavonoids (piceid and quercetin) were identified in fresh
      SCL using liquid chromatography-mass spectrometry. The total amount of identified
      phenolic acid and flavonoids was highest in steamed SCL (12.70 +/- 0.12 mg g(-1)
      on a dry matter basis, dmb). A substantial amount of chlorogenic acid (5.81 +/-
      0.16 mg g(-1) dmb), piceid (3.96 +/- 0.04 mg g(-1) dmb) and quercetin (6.06 +/-
      0.12 mg g(-1) dmb) were quantified in SCL fermented by Bacillus species, roasted
      and steamed, respectively (P < 0.05). The oxygen radical absorbance capacity
      (ORAC) value was greater in microbial fermented SCL than in others, with the
      exception of Saccharomyces cerevisiae and Aspergillus oryzae. However, vitamin C
      equivalent antioxidant capacity (VCEAC) was highest in SCL fermented by
      Aspergillus oryzae. CONCLUSION: Results from our study suggest that the microbial
      fermentation processing method could improve accessibility to extraction of
      phenolic acids and flavonoid content and radical scavenging capacity.

PMID- 25754765
TI  - Protective effects of edaravone combined puerarin on inhalation lung injury
      induced by black gunpowder smog.
AB  - OBJECTIVE: The present study aimed to investigate the combined effects of
      puerarin with edaravone on inhalation lung injury induced by black gunpowder
      smog. MATERIALS AND METHODS: Male Wistar rats were divided into five groups
      (control group, edaravone group, puerarin group, edaravone combined with puerarin
      group and inhalation group). The severity of pulmonary injuries was evaluated
      after inducing acute lung injury. Arterial blood gas, inflammatory cytokines,
      biochemical, parameters, cell counting, W/D weight ratio and histopathology were
      analyzed. Results in lung tissues, either edaravone or puerarin treatment alone
      showed significant protective effects against neutrophil infiltration and tissue
      injury, as demonstrated by myeloperoxidase activity and histopathological
      analysis (all p<0.05). In addition, combined treatment with both edaravone and
      puerarin demonstrated additive protective effects on smog-induced lung injury,
      compared with single treatment. CONCLUSIONS: Combination of edaravone and
      puerarin shows promise as a new treatment option for acute lung injury/acute
      respiratory distress syndrome patients.

PMID- 25754766
TI  - Role of aldehyde dehydrogenase in hypoxic vasodilator effects of nitrite in rats
      and humans.
AB  - BACKGROUND AND PURPOSE: Hypoxic conditions favour the reduction of nitrite to
      nitric oxide (NO) to elicit vasodilatation, but the mechanism(s) responsible for
      bioconversion remains ill defined. In the present study, we assess the role of
      aldehyde dehydrogenase 2 (ALDH2) in nitrite bioactivation under normoxia and
      hypoxia in the rat and human vasculature. EXPERIMENTAL APPROACH: The role of
      ALDH2 in vascular responses to nitrite was studied using rat thoracic aorta and
      gluteal subcutaneous fat resistance vessels from patients with heart failure (HF;
      16 patients) in vitro and by measurement of changes in forearm blood flow (FBF)
      during intra-arterial nitrite infusion (21 patients) in vivo. Specifically, we
      investigated the effects of (i) ALDH2 inhibition by cyanamide or propionaldehyde
      and the (ii) tolerance-independent inactivation of ALDH2 by glyceryl trinitrate
      (GTN) on the vasodilator activity of nitrite. In each setting, nitrite effects
      were measured via evaluation of the concentration-response relationship under
      normoxic and hypoxic conditions in the absence or presence of ALDH2 inhibitors.
      KEY RESULTS: Both in rat aorta and human resistance vessels, dilatation to
      nitrite was diminished following ALDH2 inhibition, in particular under hypoxia.
      In humans there was a non-significant trend towards attenuation of nitrite
      mediated increases in FBF. CONCLUSIONS AND IMPLICATIONS: In human and rat
      vascular tissue in vitro, hypoxic nitrite-mediated vasodilatation involves ALDH2.
      In patients with HF in vivo, the role of this enzyme in nitrite bioactivation is
      at the most, modest, suggesting the involvement of other more important
      mechanisms.

PMID- 25754767
TI  - Prognostic significance of polo-like kinases in retinoblastoma: correlation with
      patient outcome, clinical and histopathological parameters.
AB  - BACKGROUND: Retinoblastoma is evolving, but it is still a therapeutic challenge
      for pediatric oncologists. Polo-like kinases (PLKs) plays an important role in
      cell cycle events. They play a crucial role in cell proliferation which may lead
      to tumour formation. The objective of this study is to investigate the role of
      PLK1 and PLK3 proteins in human retinoblastoma tissues. DESIGN: Non-randomized,
      prospective study was performed in the Dr R. P. Centre for Ophthalmic Sciences,
      All India Institute of Medical Sciences, New Delhi, India. PARTICIPANTS: This
      study included 74 primary enucleated retinoblastoma tissues. METHODS: Expression
      of PLK1 and PLK3 protein were assessed in primary enucleated retinoblastoma
      tissues by immunohistochemistry and western blotting. MAIN OUTCOME MEASURES:
      Expression of PLK1 and PLK3 protein were correlated with clinical and
      histopathological parameters, tumour staging and overall survival of patients.
      RESULTS: Immunohistochemical results revealed expression of PLK1 in 47/74
      (63.51%) cases and PLK3 in 31/74 (41.89%) cases. Western blotting confirmed the
      immunoreactivity results. Expression of PLK1 showed correlation with poor
      differentiation and tumour invasion. In addition, PLK1 was statistically
      significant with massive choroidal invasion, whereas PLK3 did not correlate with
      any of the clinical or histopathological parameters. There was no statistical
      correlation in the overall survival of patients with PLK1 and PLK3 expression.
      CONCLUSIONS: PLK1 expression was associated with poor tumour differentiation and
      histopathological high-risk factors. These proteins may be involved in
      tumorigenesis and progression of disease. These results suggest that PLK1 may act
      as a potential therapeutic target and a promising marker for developing potent
      small molecule inhibitors of PLK isoforms in retinoblastoma.

PMID- 25754768
TI  - Associations between economic loss, financial strain and the psychological status
      of Wenchuan earthquake survivors.
AB  - This study examines the effects of economic loss on the life satisfaction and
      mental health of Wenchuan earthquake survivors. Economic loss is measured by
      earthquake impacts on the income and houses of the survivors. The correlation
      analysis shows that earthquake impact on income is significantly correlated with
      life satisfaction and depression. The regression analyses indicate that
      earthquake impact on income is indirectly associated with life satisfaction and
      depression through its effect on financial strain. The research highlights the
      importance of coping strategies in maintaining a balance between economic status
      and living demands for disaster survivors. 

PMID- 25754769
TI  - Acute decrease in the stiffness of resting muscle belly due to static stretching.
AB  - The purpose of the study was to examine the acute effect of static stretching
      exercise on the resting stiffness of gastrocnemius muscle belly. Ten healthy
      young adults performed standing wall stretching in dorsiflexion for 1 min at a
      time and repeated five times. Before and after stretching, the shear modulus was
      measured in medial and lateral heads of the resting gastrocnemius muscle with
      ultrasound shear-wave elastography. After the stretching, dorsiflexion range of
      motion (ROM) of the ankle joint increased (P < 0.01) by 3.9 degrees  and returned
      in 20 min. Immediately after stretching, shear modulus decreased (P < 0.01) by
      14%, compared with before stretching across muscle heads. The decrease in shear
      modulus returned in 20 min after stretching. In the comparison group of 10
      additional subjects, the standing intervention without stretching had no
      influence on these measures. There was a negative correlation between
      dorsiflexion ROM and shear modulus in either head before and after stretching.
      The results demonstrate the transient decreases in the stiffness of the resting
      gastrocnemius muscle belly and indicate that joint flexibility is greater in
      individuals with lower resting stiffness of the muscle belly.

PMID- 25754770
TI  - Potential chitosan-coated alginate nanoparticles for ocular delivery of
      daptomycin.
AB  - Daptomycin may offer an antibacterial alternative for the treatment of
      endophthalmitis caused by methicillin-resistant Staphylococcus aureus (MRSA) and
      other potential agents. In the present project, mucoadhesive chitosan-coated
      alginate (CS-ALG) nanoparticles are proposed as an effective delivery system for
      daptomycin permeation across ocular epithelia, with potential for the treatment
      of bacterial endophthalmitis. CS-ALG nanoparticles were prepared by ionotropic
      pre-gelation of an alginate core followed by chitosan polyelectrolyte
      complexation, and characterized regarding particle size, polydispersity, and zeta
      potential. The encapsulation efficiency was determined and antimicrobial activity
      was also tested after encapsulation of the antibiotic. Also, in vitro ocular
      permeability of free daptomycin and encapsulation into chitosan and CS-ALG
      nanoparticles was evaluated using ocular epithelial cell culture models.
      Formulated daptomycin-loaded CS-ALG nanoparticles were negatively charged, with a
      size range of 380-420 nm, suitable for ocular application. The encapsulation
      efficiency was between 79 and 92 %, with decreasing alginate:daptomycin mass
      ratios. The antibacterial activity of daptomycin against major microorganisms
      responsible for bacterial endophthalmitis was not affected by encapsulation into
      nanoparticles. Daptomycin permeability was up to 16 % (chitosan nanoparticles)
      and 9 % (CS-ALG nanoparticles) through corneal cell monolayer, and 18 % (chitosan
      nanoparticles) and 12 % (CS-ALG nanoparticles) for retinal cell monolayer after 4
      h, demonstrating epithelial retention of the drug compared to free drug. The
      developed daptomycin-loaded CS-ALG nanoparticles seem to be an interesting and
      potential system for ocular daptomycin delivery and treatment of bacterial
      endophthalmitis.

PMID- 25754771
TI  - Does prenatal MRI enhance fetal diagnosis of intra-abdominal cysts?
AB  - OBJECTIVE: The aim of this study was to evaluate the contribution of prenatal
      magnetic resonance imaging (MRI) to ultrasound (US) in the prenatal diagnosis of
      intra-abdominal cystic masses, correlated with the postnatal diagnosis. METHODS:
      In this retrospective, observational study, prenatal MRI and US diagnoses were
      compared with postnatal diagnoses. MRI was performed in 56 fetuses with intra
      abdominal cyst diagnosed by US between 2004 and 2013. Final diagnosis, revealed
      by postnatal evaluation, was obtained for 49 of them and was taken as the
      reference. MRI was evaluated as superior, equal, or inferior to US. RESULTS: An
      accurate diagnosis was provided by US in 25 cases (51%) and by MRI in 36 out of
      the 49 cases (73.4%). MRI corrected the US diagnosis in 13 cases (26.5%) by
      providing a more precise localization or additional etiologic information. In two
      cases (4%), MRI wrongly changed the diagnosis correctly made by US. CONCLUSION:
      Prenatal MRI better characterized the nature of abdominal cystic lesions
      previously diagnosed by US in 13 cases. This enhanced postnatal therapeutic
      planning and so improved parental counseling and pregnancy management.

PMID- 25754772
TI  - Commentary on 'the cumulative incidence of graft infection after primary
      prosthetic aortic reconstruction in the endovascular era'.

PMID- 25754773
TI  - The effect of endovenous laser ablation of incompetent perforating veins and the
      great saphenous vein in patients with primary venous disease.
AB  - OBJECTIVE/BACKGROUND: This study aimed to investigate the clinical results and
      fate of incompetent perforating veins (IPVs) following treatment of superficial
      venous insufficiency, with or without endovenous laser ablation (EVLA) of IPVs.
      METHODS: A retrospective analysis of patients with primary venous insufficiency
      (PVI) was conducted in a single institution from January, 2010 to December, 2011.
      IPVs were found in 311 patients (376 limbs). Among these, 132 patients (156
      limbs) were treated with EVLA of IPVs and varicose vein surgery, and the
      remaining 179 patients (220 limbs) were treated with varicose vein surgery alone
      and served as controls. The fate of the IPVs, complications and clinical results
      were evaluated. RESULTS: The technical success rate of EVLA of IPVs was 100%.
      There was no statistical difference in complications between the two groups. At 1
      year follow up, 68 perforators were recanalized and still incompetent in the EVLA
      treated IPV group compared with 437 incompetent perforators in the untreated IPV
      group (18.7% vs. 92.6%; p < .001). A faster median ulcer healing time (1.40
      months) was found in the EVLA treated IPV group (95% confidence interval [CI]
      1.15-1.66 vs. 3.30 months [95% CI 2.50-4.10]; p = .001), even though no
      statistical difference in the 12 month ulcer healing rate was observed between
      the two groups (p = .584). There were no significant differences between the two
      groups for varicose vein recurrence rates or changes in the Venous Clinical
      Severity Score (VCSS). CONCLUSION: EVLA was safe and effective in reducing the
      number of IPVs in PVI. However, the addition of IPV EVLA had no effect on ulcer
      healing rate, VCSS or varicose vein recurrence at 1 year follow up.

PMID- 25754774
TI  - Description of quantum coherence in thermodynamic processes requires constraints
      beyond free energy.
AB  - Recent studies have developed fundamental limitations on nanoscale
      thermodynamics, in terms of a set of independent free energy relations. Here we
      show that free energy relations cannot properly describe quantum coherence in
      thermodynamic processes. By casting time-asymmetry as a quantifiable, fundamental
      resource of a quantum state, we arrive at an additional, independent set of
      thermodynamic constraints that naturally extend the existing ones. These
      asymmetry relations reveal that the traditional Szilard engine argument does not
      extend automatically to quantum coherences, but instead only relational
      coherences in a multipartite scenario can contribute to thermodynamic work. We
      find that coherence transformations are always irreversible. Our results also
      reveal additional structural parallels between thermodynamics and the theory of
      entanglement. 

PMID- 25754775
TI  - Mitochondrial genome sequences reveal evolutionary relationships of the
      Phytophthora 1c clade species.
AB  - Phytophthora infestans is one of the most destructive plant pathogens of potato
      and tomato globally. The pathogen is closely related to four other Phytophthora
      species in the 1c clade including P. phaseoli, P. ipomoeae, P. mirabilis and P.
      andina that are important pathogens of other wild and domesticated hosts. P.
      andina is an interspecific hybrid between P. infestans and an unknown
      Phytophthora species. We have sequenced mitochondrial genomes of the sister
      species of P. infestans and examined the evolutionary relationships within the
      clade. Phylogenetic analysis indicates that the P. phaseoli mitochondrial lineage
      is basal within the clade. P. mirabilis and P. ipomoeae are sister lineages and
      share a common ancestor with the Ic mitochondrial lineage of P. andina. These
      lineages in turn are sister to the P. infestans and P. andina Ia mitochondrial
      lineages. The P. andina Ic lineage diverged much earlier than the P. andina Ia
      mitochondrial lineage and P. infestans. The presence of two mitochondrial
      lineages in P. andina supports the hybrid nature of this species. The ancestral
      state of the P. andina Ic lineage in the tree and its occurrence only in the
      Andean regions of Ecuador, Colombia and Peru suggests that the origin of this
      species hybrid in nature may occur there. 

PMID- 25754776
TI  - Apical blebs on sperm storage tubule epithelial cell microvilli: their release
      and interaction with resident sperm in the turkey hen oviduct.
AB  - Located at the anterior end of the turkey hen's vagina are numerous discrete
      tubular invaginations of the surface epithelium, collectively referred to as the
      sperm storage tubules (SSTs). After mating or artificial insemination, sperm
      ascend the vagina, enter the SSTs, and over the ensuing days and weeks, gradually
      exit the SSTs and are transported to the anterior end of the oviduct to fertilize
      a daily succession of ova. Little is known regarding the cellular and molecular
      mechanisms responsible for sperm subsistence in the lumen of the SST. In this
      study, the origin of microvillus blebs (MvBs) on the apical tips of SST
      epithelial cells was examined, and their possible role in sperm survival was
      discussed. Regardless, if sperm are present or not, transmission electron
      microscopy revealed two types of microvilli differentiated by the presence or
      absence of pleomorphic unilaminar MvBs localized to their apical tips. Although
      some MvBs appeared to be discharging their contents into the SST lumen, others
      appeared to have pinched off the microvillus stem. When SSTs contained clusters
      of densely packed sperm, the sperm heads of those sperm adjacent to the SST
      epithelial cell surface were surrounded by the microvilli. Associated with the
      plasmalemma of sperm throughout the SST lumina were membrane fragments and small
      vesicles (30-130 nm in diameter), some of which appeared to have fused with
      sperm. It is concluded that the MvBs are a form of shedding vesicle released from
      the SST epithelial cell microvilli by apocrine secretion. On the basis of
      observations described herein and those of other authors, it is suggested that
      the MvBs contribute to sustained sperm storage in the SSTs by (1) supplying
      metabolic substrates used by resident sperm, (2) serving as fusogenic vehicles
      providing exogenous macromolecules that reversibly suppress sperm functions
      associated with fertilization (decapacitation?) and stabilize the sperm
      plasmalemma, and (3) acting as transport vesicles actively transporting fluid
      from the SST epithelial cells to the SST lumen.

PMID- 25754777
TI  - Indefinite integration.

PMID- 25754778
TI  - Self-neglect: a case study and implications for clinical practice.
AB  - Self-neglect is a worldwide and serious public health issue that can have serious
      adverse outcomes and is more common in older people. Cases can vary in
      presentation, but typically present as poor self-care, poor care of the
      environment and service refusal. Community nurses frequently encounter self
      neglect cases and health and social care professionals play a key role in the
      identification, management and prevention of self-neglect. Self-neglect cases can
      give rise to ethical, personal and professional challenges. The aim of this
      article is to create a greater understanding of the concept of self-neglect among
      community nurses. 

PMID- 25754779
TI  - Compression therapy and the management of lower-limb lymphoedema: the male
      perspective.
AB  - Lymphoedema and chronic oedema are managed through multiple interventions forming
      the two key stages of lymphoedema management. In the field of lymphoedema and
      chronic oedema research, the male perspective has received limited attention when
      compared with the female equivalent. Further research is needed within the UK and
      globally to address the present gap. Despite this limited focus, management
      options available to male patients do not differ significantly from female
      patients, with compression therapy being the main management option. The success
      of compression therapy and other interventions such as skin care and exercise
      depend on the patient's acceptance of the condition and the management options
      made available. This requires the development of an appropriate partnership
      between the health professional and the patient. 

PMID- 25754780
TI  - Making the complexity of community nursing visible: the Cassandra project.
AB  - The need to effectively promote safe staffing levels in community settings
      challenges commissioners and providers of services to find rigorous methods of
      capturing workforce evidence that can be systematically used to shape effective
      services and skill mix for the future. This article presents a brief review of
      current approaches and challenges to measuring community nursing workload
      activity in England. Specifically, it shows phase 1 pilot results using the
      Cassandra Matrix activity tool and review of ongoing developments and progress to
      demonstrate scalability for national implementation. As part of a much larger
      practice development project to develop community nursing, the pilot used mixed
      methods to collect 10 days of workload activity data from a self-selected sample
      of band 5-7 nurses working in general and specialist community nursing roles in
      three community organisations, and to evaluate their experiences of using the
      tool via an electronic survey. The findings indicate that the tool has
      significant potential for capturing the complexity and multiple dimensions of
      nursing work in community contexts, and phase 2 work has led to a community
      version of the tool being piloted on a larger scale across six community
      organisations. 

PMID- 25754781
TI  - Mobile working: positively engaging community nurses.
AB  - Mobile working refers to a practitioner's ability to access information systems
      and applications while 'on the move'. This relatively new concept has yielded a
      number of benefits, including the ability to access patients' electronic records
      in real time and a reduction in travelling time for clinicians, thereby improving
      efficiency within community nursing practice. For a change in practice to be
      successful, it is necessary to ensure that the proposals are discussed with the
      staff group implementing them and that appropriate help and support are provided
      during the period of transition. Maintaining engagement with community nursing
      teams may be challenging due to increasing workloads and limited resources,
      potentially affecting health professionals' ability to attend workshops and
      associated events. Considering the specific needs of the workforce requires
      consideration and planning, including provision of additional support for members
      of staff who may lack confidence in working with mobile devices. 

PMID- 25754782
TI  - Validating the 'intervention wheel' in the context of Irish public health
      nursing.
AB  - Illuminating the full range of nursing actions is a challenge for nurses
      globally; the invisibility of nursing and of public health nursing in particular
      is well documented. Visibility can be enhanced by identifying core functions of
      nursing and matching corresponding levels of interventions and outcomes. This is
      a priority for the contemporary Irish public health nursing (PHN) service. In the
      United States, public health nurses have developed an 'Intervention Wheel' naming
      public health interventions at community, systems and individual/family levels.
      This aimed to make visible the core functions of PHN practice. The values and
      beliefs underpinning the Intervention Wheel have been shown to capture the
      essence of public health nursing within the European context. In total, US nurses
      described 17 Wheel interventions by recording stories from practice. Owing to
      concern that the public health aspect of their role was not only invisible but
      was at risk of erosion, Irish PHNs decided to replicate this storytelling
      approach to provide evidence for and authenticate the 17 interventions on the
      Intervention Wheel from their day-to-day public health practice. 

PMID- 25754783
TI  - Accountability in district nursing practice: key concepts.
AB  - Public trust and confidence in district nurses is essential to the nurse-patient
      relationship that underpins effective care and treatment. That trust and
      confidence has even greater focus for district nurses who care for patients in
      their own homes. Those patients need to be able to count on the professionalism
      and probity of their district nurses. The professionalism and probity of district
      nurses is based on their accountability, which protects the public by imposing
      standards on district nurses and holds them answerable for their acts and
      omissions. This is the first of a series of articles on accountability in
      district nursing practice to mark the introduction of the revised Nursing and
      Midwifery Code on the 31 March 2015. This month's article considers the key
      concepts of accountability. 

PMID- 25754784
TI  - Ten years on from the national service framework for long-term conditions: how
      far have we come?
AB  - Aysha Mendes investigates whether the Department of Health's blueprint for
      improving care of long-term conditions in the UK has been successful amid the
      large-scale changes occurring in the NHS over recent years. 

PMID- 25754785
TI  - Knowledge of impending death and its effect on quality of dying.

PMID- 25754786
TI  - Rethinking care models.

PMID- 25754787
TI  - Outcomes of opening wedge osteotomy to correct angular deformity in little finger
      clinodactyly.
AB  - PURPOSE: To evaluate the outcomes and complications in a series of children with
      clinodactyly treated with opening wedge osteotomy of the abnormal phalanx.
      METHODS: We performed a retrospective review of all children with clinodactyly
      treated at our institution with opening wedge osteotomy of the abnormal middle
      phalanx between 2003 and 2013. Patients with concomitant pathology or prior
      surgery in the affected finger were excluded. Preoperative and postoperative
      clinical angle, radiographic angle, digital range of motion, and pain were
      compared and complications were recorded. RESULTS: We included 13 digits in 9
      patients. All had greater than 20 degrees  of preoperative clinical angulation
      (mean, 36 degrees ). Mean age at time of surgery was 11 years; mean duration of
      follow-up was 25 months (range, 12-43 mo). All digits had significant improvement
      (mean, 32 degrees ) in clinical and radiographic angles after surgery. This
      improvement was maintained at final follow-up in 12 digits. Six patients had pain
      preoperatively and no patient had pain postoperatively. One digit had a recurrent
      deformity at final follow-up and 3 digits developed stiffness at the distal
      interphalangeal joint. CONCLUSIONS: Opening wedge osteotomy is an effective
      treatment for angulation in children with clinodactyly. We counsel families
      regarding the risk of distal interphalangeal joint stiffness. TYPE OF STUDY/LEVEL
      OF EVIDENCE: Therapeutic IV.

PMID- 25754788
TI  - Soft tissue release and bilobed flap for severe radial longitudinal deficiency.
AB  - PURPOSE: To report the hand position, range of motion, functional results, and
      radiographic outcomes associated with treating radial longitudinal deficiency
      with release of constricting or deforming soft tissue and resurfacing of the
      radial skin deficiency with a bilobed flap. METHODS: We recalled and reviewed
      patients with at least a 3-year follow-up who had undergone soft-tissue release
      and coverage with a bilobed flap. The study group consisted of 16 patients and 18
      wrists. All patients underwent follow-up examination and radiographs. Outcome
      measures using Pediatric Outcomes Data Collection Instrument (PODCI),
      Disabilities of the Arm, Shoulder, and Hand (DASH), and visual analogue scale
      (VAS) scores were recorded. RESULTS: At a mean of 9.2 years follow-up, the
      average final resting wrist radial deviation angle was 64 degrees  compared with
      88 degrees  preoperatively. The average active wrist flexion-extension arc was 73
      degrees . Average DASH score was 27 (range, 5-54). PODCI global was 88 (range, 75
      97), PODCI happiness was 86 (range, 70-100), and VAS overall satisfaction (range,
      0-10) was 1.2 (range, 0-8). At final follow-up, no physeal growth arrests were
      noted on radiographs, and no patients to date have required ulnocarpal
      arthrodesis. CONCLUSIONS: Soft-tissue release and coverage with a bilobed flap
      should be considered in the treatment algorithm for patients with radial
      longitudinal deficiency. Outcome measures show that these patients maintain
      useful active motion, and along with their parents, are satisfied with both the
      appearance and function. Some recurrence of radial deviation was noted, which was
      similar to results previously reported following centralization/radialization
      procedures, although with a lower inherent risk of both physeal injury to the
      ulna and stiffness. In addition, potential future procedures are not compromised
      by this surgical approach. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV.

PMID- 25754789
TI  - Affected and contralateral hand strength and dexterity measures in children with
      hemiplegic cerebral palsy.
AB  - PURPOSE: To determine how the affected hemiplegic hand and contralateral dominant
      hand in children with hemiplegic cerebral palsy compare with age-matched norms
      for grip strength, pinch strength, and dexterity. METHODS: We enrolled 37
      children with hemiplegic cerebral palsy (26 boys; average age, 9.8 y). Grip and
      pinch strength and Box and Blocks Test for dexterity were measured in both hands.
      Affected and contralateral hands results were analyzed and compared with each
      other and with norms for age and sex. RESULTS: Affected hands had significantly
      less grip and pinch strength than the contralateral hands. Subjects transported
      significantly fewer blocks in one minute with the Box and Blocks Test (mean, 10.8
      blocks) with the affected hand than the contralateral hand. Compared with
      normative values, affected-side grip and pinch strengths were significantly less,
      whereas contralateral hand grip and pinch strengths were similar. Dexterity in
      both affected and contralateral hands was significantly less than normative
      values. Decreased dexterity in the contralateral hand was correlated with
      decreased nonverbal intelligence quotient. CONCLUSIONS: Dexterity of the
      contralateral hand is diminished in children with hemiplegia. Assessment of the
      contralateral hand may reveal opportunities for therapeutic intervention that
      improve fine motor function. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV.

PMID- 25754790
TI  - Management of osteoarthrosis of the thumb joints.
AB  - We present current concepts and evidence to optimize diagnosis and management of
      osteoarthritis in the thumb joints. Numerous options and controversies exist for
      surgical treatment of carpometacarpal joint arthritis. Fewer options exist for
      metacarpophalangeal joint arthritis. Surgical treatment for interphalangeal
      arthritis is mainly arthrodesis. 

PMID- 25754791
TI  - Investigation on the interaction of nanoAg with Cu-Zn SOD.
AB  - Silver nanoparticles (nanoAg) are used more and more widely, particularly because
      of their antimicrobial properties. The effect of exposure to nanoAg on the
      structure of superoxide dismutase (SOD) was thoroughly investigated using
      fluorescence measurements, synchronous fluorescence spectroscopy, steady-state
      and time-resolved fluorescence quenching measurements, UV/Vis absorption
      spectroscopy, resonance light scattering (RLS), circular dichroism (CD),
      isothermal titration calorimetry (ITC) and high-resolution transmission electron
      microscopy (HRTEM). Through van der Waal's force, nanoAg interacted with Cu-Zn
      SOD and influenced the active site by inducing structural changes, which
      influenced the function of SOD. The fluorescence studies show that both static
      and dynamic quenching processes occur. This paper provides reference data for
      toxicological studies of nanoAg, which are important in the future development of
      nanotechnology.

PMID- 25754792
TI  - Validation of the Geriatric Oral Health Assessment Index in complete denture
      wearers.
AB  - To perform a validation of the Geriatric Oral Health Assessment Index (GOHAI) for
      complete denture wearers and present a proposal for estimation of perceived oral
      health. This is a cross-sectional study with non-probabilistic sampling. A total
      of 211 subjects with a mean age of 62.5 (s.d. = 11.4) years participated, being
      169 female. The GOHAI was applied in a personal interview. The
      construct/convergent/discriminant validity was tested using structural equation
      modelling. Confirmatory factor analysis was used to verify the fit of three
      proposals of the GOHAI: three-factor, one-factor and second-order hierarchical
      models. The stability of the models was evaluated in independent samples. The
      three-factor model presented an inadequate fit, and items 3, 4 and 9 were
      removed. The new structure presented an acceptable fit and strong invariance in
      independent samples. The convergent, discriminant validity and internal
      consistency were below adequate. The one-factor model presented an adequate fit
      to the sample. Convergent validity was compromised. A strong invariance of the
      one-factor model was observed. To calculate the overall scores of the GOHAI
      factors (three-factor model) or of the oral health perception (one-factor model),
      a matrix of regression weights for each item in the model was presented as a
      suggestion. We found an adequate fit of the both structures of the GOHAI for
      denture wearers, but the three-factor structure was more parsimonious. We
      suggested considering the weights of the regression model to calculate the
      overall score of perceived oral health or of its factors in different samples. 

PMID- 25754793
TI  - Effects of VEGF and MSCs on vascular regeneration in a trauma model in rats.
AB  - In the human body, vascular injuries that are caused by trauma, vessel lumen
      stenosis, and occlusions are often irreversible and can lead to sequelae
      formation as the vessels cannot reproduce fast enough. To solve this problem, the
      blood flow must be returned to the region as fast as possible. The adipose tissue
      contains progenitor cells with angiogenic potential and can be used to resolve
      the issue. In the present study, mesenchymal stem cells (MSCs) derived from rat
      adipose tissue, vascular endothelial growth factor (VEGF), and their mixture were
      applied on the dorsum of a rat, which was traumatized and its contribution to
      vascular regeneration was reviewed. No application was made to the control group.
      The results showed that the percentage of necrotic area was significantly lower
      in the MSC group than that of all the other groups. When the VEGF group was
      compared to the VEGF + MSCs, the percentage of necrotic area was observed to be
      similiar. However, VEGF showed effects only when a large quantites of VEGF was
      applied to the flap area. VEGF could not fully respond to the needs, whereas MSCs
      can produce VEGF according to the needs of tissue. This makes them superior to
      stem cells. 

PMID- 25754794
TI  - Contrast-enhanced ultrasonography to assess blood perfusion of skeletal muscles
      in normal dogs.
AB  - This study evaluated perfusion of skeletal muscle using contrast enhanced
      ultrasonography in humerus, radius, femur and tibia in normal dogs. Contrast
      enhanced ultrasonography for each region was performed after injecting 0.5 mL and
      1 mL of contrast medium (SonoVue) in every dog. Blood perfusion was assessed
      quantitatively by measuring the peak intensity, time to the peak intensity and
      area under the curve from the time-intensity curve. Vascularization in skeletal
      muscle was qualitatively graded with a score of 0-3 according to the number of
      vascular signals. A parabolic shape of time-intensity curve was observed from
      muscles in normal dogs, and time to the peak intensity, the peak intensity and
      area under the curve of each muscle were not significantly different according to
      the appendicular regions examined and the dosage of contrast agent administered.
      This study reports that feasibility of contrast enhanced ultrasonography for
      assessment of the muscular perfusion in canine appendicular regions. 

PMID- 25754795
TI  - Non-enzymatic ribonucleotide reduction in the prebiotic context.
AB  - Model studies of prebiotic chemistry have revealed compelling routes for the
      formation of the building blocks of proteins and RNA, but not DNA. Today,
      deoxynucleotides required for the construction of DNA are produced by reduction
      of nucleotides catalysed by ribonucleotide reductases, which are radical enzymes.
      This study considers potential non-enzymatic routes via intermediate radicals for
      the ancient formation of deoxynucleotides. In this context, several mechanisms
      for ribonucleotide reduction, in a putative H2 S/HS(.) environment, are
      characterized using computational chemistry. A bio-inspired mechanistic cycle
      involving a keto intermediate and HSSH production is found to be potentially
      viable. An alternative pathway, proceeding through an enol intermediate is found
      to exhibit similar energetic requirements. Non-cyclical pathways, in which HSS(.)
      is generated in the final step instead of HS(.) , show a markedly increased
      thermodynamic driving force (ca. 70 kJ mol(-1) ) and thus warrant serious
      consideration in the context of the prebiotic ribonucleotide reduction. 

PMID- 25754796
TI  - Involvement of the NO/cGMP/KATP pathway in the antinociceptive effect of the new
      pyrazole 5-(1-(3-fluorophenyl)-1H-pyrazol-4-yl)-2H-tetrazole (LQFM-021).
AB  - The pyrazol compounds are known to possess antipyretic, analgesic and anti
      inflammatory activities. This study was conducted to investigate the peripheral
      antinociceptive effect of the pyrazole compound 5-(1-(3-Fluorophenyl)-1H-pyrazol
      4-yl)-2H-tetrazole (LQFM-021) and involvement of opioid receptors and of the
      NO/cGMP/K(ATP) pathway. The oral treatments in mice with LQFM-021 (17, 75 or 300
      mg/kg) decreased the number of writhing. In the formalin test, the treatments
      with LQFM-021 at doses of 15, 30 and 60 mg/kg reduced the licking time at both
      neurogenic and inflammatory phases of this test. The treatment of the animals
      with LQFM-021 (30 mg/kg) did not have antinociceptive effects in the tail-flick
      and hot plate tests. Furthermore, pre-treatment with naloxone (3 mg/kg i.p.), L
      name (10 mg/kg i.p.), ODQ (10 mg/kg i.p.) or glibenclamide (3 mg/kg i.p.)
      antagonized the antinociceptive effect of LQFM-021 in both phases of the formalin
      test. In addition, it was also demonstrated that the treatments of mice with LQFM
      021(15, 30 and 60 mg/kg) did not compromise the motor activity of the animals in
      the chimney test. Only the highest dose used in the antinociceptive study
      promoted changes in the open field test and pentobarbital-induced sleep test,
      thus ruling out possible false positive effects on nociception tests. Our data
      suggest that the peripheral antinociception effects of the LQFM-021 were mediated
      through the peripheral opioid receptors with activation of the NO/cGMP/KATP
      pathway.

PMID- 25754797
TI  - Identification of a novel allele HLA-C*12:138 in Russian patient by haplotype
      specific sequence-based typing.
AB  - HLA-C*12:138 differs from HLA-C*12:03:01:01 by a single change, resulting in an
      amino acid substitution. 

PMID- 25754798
TI  - Malformed aortic valve mimicking type A aortic dissection.

PMID- 25754799
TI  - Liver enzyme levels and hepatic iron content in Fatty liver: a noninvasive
      assessment in general population by T2* mapping.
AB  - RATIONALE AND OBJECTIVES: Existing evidence suggests potential contribution of
      iron in pathogenesis of nonalcoholic fatty liver disease (NAFLD). We aimed to
      investigate whether hepatic iron content correlates with liver enzyme levels in
      NAFLD using a noninvasive magnetic resonance imaging (MRI) technique. MATERIALS
      AND METHODS: Subjects from Golestan Cohort Study were randomly selected.
      Diagnosis of NAFLD was made by combination of ultrasound and MRI. Subjects with
      NAFLD were divided into two groups with high (H-NAFLD) and low (L-NAFLD) enzyme
      level according to 95th percentile of alanine aminotransferase (ALT) value in
      normal population. Quantitative T2* maps of entire cross-sectional area of liver
      were calculated on pixel-by-pixel basis using a semiautomated software. RESULTS:
      A total of 207 subjects were enrolled. Mean T2* values were significantly lower
      in NAFLD group than controls (P < .001) indicating higher iron content. Male
      subjects with H-NAFLD had statistically lower T2* values than those with L-NAFLD
      in multivariate analysis (odds ratio, 0.74; 95% confidence interval [CI], 0.58
      0.95), whereas this was not observed in women. Unlike women, there was
      significant negative correlation between ALT levels and T2* values in men with H
      NAFLD (r = -0.66, P = .01). Every 1-millisecond decrement in T2* value was
      associated with 6.37 IU/L increase in ALT level (95% CI, 1.8-10.9, P = .01) in
      men with H-NAFLD. CONCLUSIONS: Higher hepatic iron in men with H-NAFLD, estimated
      by T2* mapping, may support the role of iron in possible progression of simple
      steatosis to nonalcoholic steatohepatitis. Lack of such correlation in women
      could be attributed to relatively lower iron storage or other mechanisms rather
      than iron.

PMID- 25754800
TI  - Automatic determination of differential coronary artery motion minima for cardiac
      computed tomography optimal phase selection.
AB  - RATIONALE AND OBJECTIVES: Selecting the optimal phase for coronary artery
      evaluation can be challenging, especially at higher heart rates, given that the
      optimal phase may differ for each of the coronary arteries. This study aimed to
      evaluate a novel vessel-specific algorithm which automatically outputs the
      minimum motion phase per coronary artery. MATERIALS AND METHODS: The study
      included 44 patients who underwent 256-slice cardiac computed tomography for
      evaluation of chest pain. End-systolic and mid-diastolic minimal motion phases
      were automatically calculated by a previously validated global motion algorithm
      and by a new vessel-specific algorithm which calculates the minimum motion for
      each of the three main coronary arteries, separately. Two readers blindly
      evaluated all coronary segments for image quality. Median scores per coronary
      artery were compared by the Wilcoxon signed rank test. RESULTS: The variation,
      per patient, between the optimal phases of the three coronary arteries was 5.0 +/
      4.5% (1%-22%) for end systole and 4.8 +/- 4.1% (0%-19%) for mid diastole. The
      mean image quality scores per coronary artery were 4.0 +/- 0.61 for the vessel
      specific approach and 3.80 +/- 0.69 for the global phase selection (P < .001).
      Overall, 46 of 122 arteries had a better score with the vessel-specific approach
      and five with the standard global approach. Interreader agreement was substantial
      (k = 0.72). CONCLUSIONS: This study has shown that multiple phases are required
      to ensure optimal image quality for all three coronary arteries and that a vessel
      specific phase selection algorithm achieves superior results to the standard
      global approach.

PMID- 25754801
TI  - Satisfaction of imaging report rendered in emergency setting: a survey of
      radiology and referring physicians.
AB  - RATIONALE AND OBJECTIVES: To determine physicians' preference toward three types
      of structured imaging reports (basic structured report [BSR], itemized report
      [IR], and point-and-click report [PCR]) used in emergency radiology. MATERIALS
      AND METHODS: Survey questions were created and considered valid and reliable
      based on index of item objective congruence from three specialists (>0.75) and a
      pilot of 25 subjects (Cronbach alpha, 0.83-1.00). Respondents included trainees
      and attendings in radiology and referring physicians working in the academic
      emergency department at the time of survey rollout. They were provided report
      examples of each type and asked to complete a questionnaire consisting of the
      following five parts: demographics, necessity of imaging report, report quality
      (content, format and organization, and language), process of reporting, and
      components of imaging report. For rating scores, the higher value means the
      higher preference and agreement. RESULTS: The survey received 79.5% response
      rate. Respondents included 101 physicians (mean age, 29.4 years; 61 radiology
      physicians and 40 referring physicians; 81 trainees and 20 attending). Overall,
      IR was preferred over PCR and BSR by all physicians with scores (out of 10) as
      follows: IR, 7.62-8.83; PCR, 6.62-8.55; BSR, 5.23-6.65; P < .001. IR received
      scores (out of 5) of 4.03-4.37, PCR 3.32-4.52, and BSR 2.59-3.86 for report
      quality. For process of reporting, IR had scores (out of 5) of 3.80-4.56, PCR
      2.79-4.09, and BSR 2.32-3.56. CONCLUSIONS: In emergency setting, physicians
      preferred IR over PCR and BSR. IR and PCR were equal in report quality metrics,
      but IR was most preferred in the process of reporting. BSR ranked last in both
      quality and process.

PMID- 25754802
TI  - OsNAC2 encoding a NAC transcription factor that affects plant height through
      mediating the gibberellic acid pathway in rice.
AB  - Plant height and flowering time are key agronomic traits affecting yield in rice
      (Oryza sativa). In this study, we investigated the functions in rice growth and
      development of OsNAC2, encoding a NAC transcription factor in rice. Transgenic
      plants that constitutively expressed OsNAC2 had shorter internodes, shorter
      spikelets, and were more insensitive to gibberellic acid (GA(3)). In addition,
      the levels of GAs decreased in OsNAC2 overexpression plants, compared with the
      wild-type. Moreover, flowering was delayed for approximately 5 days in transgenic
      lines. The transcription of Hd3a, a flowering-time related gene, was suppressed
      in transgenic lines. In addition, transgenic Arabidopsis plants expressing OsNAC2
      were also more insensitive to GA(3). The expression levels of GA biosynthetic
      genes OsKO2 and OsKAO were repressed. The expression of OsSLRL, encoding a
      repressor in the GA signal pathway, and OsEATB, which encodes a repressor of GA
      biosynthesis, were both enhanced. Western blotting indicated that DELLA also
      accumulated at the protein level. Dual-luciferase reporter analyses, yeast one
      hybrid assays and ChIP-qPCR suggested that OsNAC2 directly interacted with the
      promoter of OsEATB and OsKO2. Taken together, we proposed that OsNAC2 is a
      negative regulator of the plant height and flowering time, which acts by directly
      regulating key genes of the GA pathway in rice.

PMID- 25754803
TI  - Structural analysis reveals the substrate-binding mechanism for the expanded
      substrate specificity of mutant meso-diaminopimelate dehydrogenase.
AB  - A meso-diaminopimelate dehydrogenase (DAPDH) from Clostridium tetani E88
      (CtDAPDH) was found to have low activity toward the D-amino acids other than its
      native substrate. Site-directed mutagenesis similar to that carried out on the
      residues mutated by Vedha-Peters et al. resulted in a mutant enzyme with highly
      improved catalytic ability for the synthesis of D-amino acids. The crystal
      structures of the CtDAPDH mutant in apo form and in complex with meso
      diaminopimelate (meso-DAP), D-leucine (D-leu), and 4-methyl-2-oxopentanoic acid
      (MOPA) were solved. meso-DAP was found in an area outside the catalytic cavity;
      this suggested a possible two-step substrate-binding mechanism for meso-DAP. D
      leu and MOPA each bound both to Leu154 and to Gly155 in the open form of CtDAPDH,
      and structural analysis revealed the molecular basis for the expanded substrate
      specificity of the mutant meso-diaminopimelate dehydrogenases. 

PMID- 25754804
TI  - Asian neurology and stroke.

PMID- 25754805
TI  - Bilateral Marcus Gunn jaw-winking syndrome.

PMID- 25754806
TI  - Growth hormone treatment for childhood short stature and risk of stroke in early
      adulthood.

PMID- 25754807
TI  - Residency training: a failed lumbar puncture is more about obesity than lack of
      ability.
AB  - OBJECTIVE: To identify factors influencing the success of lumbar puncture (LP)
      performed by neurology residents in an outpatient clinic. BACKGROUND: There is a
      need to understand the specific influence of patient or operator characteristics
      in LP performance in order to identify situations at high risk for failure that
      could benefit from compensatory interventions. METHODS: We performed a
      retrospective analysis of all consecutive patients who underwent elective LP in
      the Neurology Clinic at the University of Iowa between 2009 and 2012. We recorded
      demographic, anthropometric, and clinical information, and the level of training
      of the resident performing the procedure. Outcomes measure was unsuccessful LP,
      defined as no quantifiable CSF. This study was previously approved by the
      University of Iowa institutional review board. RESULTS: A total of 328 patients
      (59% women) were included. Men were significantly older than women, and the
      indication of the procedure differed by sex. Headache or possible multiple
      sclerosis were more common indications in women than in men. Nineteen percent of
      the LPs were unsuccessful. We found a strong correlation between patient body
      mass index (BMI) and unsuccessful outcome (p < 0.0001). Age of the patient and
      level of training of the operator did not predict unsuccessful LP. CONCLUSIONS:
      Patient BMI is the key factor that determines an unsuccessful LP by neurology
      residents in an outpatient setting, an association that might be applicable to
      different clinical settings. The high failure rate in patients with BMI >35
      suggests that implementing compensatory interventions such as the use of imaging
      guidance might be cost-effective and better tolerated by these patients.

PMID- 25754808
TI  - Emerging subspecialties in neurology: autonomic disorders.

PMID- 25754809
TI  - Teaching video NeuroImages: hand tremor, tongue and perioral fasciculation in a
      patient with Kennedy disease.

PMID- 25754810
TI  - Teaching video NeuroImages: tongue fasciculations in spinal muscular atrophy.

PMID- 25754811
TI  - Time trends in BMI, body fatness, and adiposity rebound among boys from Krakow
      (Poland) from 1983 to 2010.
AB  - OBJECTIVES: The prevalence of childhood obesity has been increasing during the
      last decades in many countries, but less is known about secular trends in growth
      curves covering the whole childhood span. The main purpose of this study was to
      explore changes in body weight, height, BMI, percent body fat (%BF), adiposity
      rebound (AR), and pubertal timing in boys from Krakow between 1983 and 2010.
      METHODS: Totally, 4,986 boys (3-18 years) were measured during cross-sectional
      studies. Using the results of height, weight, and skinfold measurements, BMI and
      %BF were calculated. The LMS method was used to construct BMI and %BF
      percentiles. Three cut-off points were distinguished in individual age groups of
      the subjects-below the 15th percentile, 50th percentile, and above the 85th
      percentile. The mean age at pubarche was calculated by the probit method.
      RESULTS: The boys from 2010 were taller and heavier than the boys from 1983.
      Before the time of AR, boys from 2010 had lower BMI, but after AR had higher BMI
      than boys from 1983. An earlier AR appeared in all BMI 2010 percentile curves as
      compared to 1983. The boys from 2010 also showed an acceleration of sexual
      maturation and earlier Tanner Stage II, equaling 11.80 years. CONCLUSIONS: In
      boys from 2010, AR occurs earlier than in boys from 1983. Changes in timing of AR
      cannot be explained only by changes in degree of body adiposity. Early AR could
      be a marker of the acceleration of development.

PMID- 25754812
TI  - When infants talk, infants listen: pre-babbling infants prefer listening to
      speech with infant vocal properties.
AB  - To learn to produce speech, infants must effectively monitor and assess their own
      speech output. Yet very little is known about how infants perceive speech
      produced by an infant, which has higher voice pitch and formant frequencies
      compared to adult or child speech. Here, we tested whether pre-babbling infants
      (at 4-6 months) prefer listening to vowel sounds with infant vocal properties
      over vowel sounds with adult vocal properties. A listening preference favoring
      infant vowels may derive from their higher voice pitch, which has been shown to
      attract infant attention in infant-directed speech (IDS). In addition, infants'
      nascent articulatory abilities may induce a bias favoring infant speech given
      that 4- to 6-month-olds are beginning to produce vowel sounds. We created infant
      and adult /i/ ('ee') vowels using a production-based synthesizer that simulates
      the act of speaking in talkers at different ages and then tested infants across
      four experiments using a sequential preferential listening task. The findings
      provide the first evidence that infants preferentially attend to vowel sounds
      with infant voice pitch and/or formants over vowel sounds with no infant-like
      vocal properties, supporting the view that infants' production abilities
      influence how they process infant speech. The findings with respect to voice
      pitch also reveal parallels between IDS and infant speech, raising new questions
      about the role of this speech register in infant development. Research exploring
      the underpinnings and impact of this perceptual bias can expand our understanding
      of infant language development.

PMID- 25754813
TI  - Abrin poisoning in an 18-month-old child.
AB  - BACKGROUND: When discussing known poisons and their clinical consequences, few
      physicians are aware of the deadly poison abrin. The common symptoms of abrin
      toxicity include nausea, vomiting, abdominal pain, and diarrhea with or without
      bloody stool. However, with an estimated fatal human dose of less than 1
      microgram/kg, death due to complications such as liver failure, renal failure,
      and cerebral edema are possible. CASE REPORT: An 18-month-old male presented to
      the emergency department with an abrupt onset of fever, vomiting, diarrhea, and
      dehydration. The parents had assumed the child was suffering from a severe
      gastroenteritis until they noticed 3 consecutive diapers containing colorful
      seeds that were identified by poison control as belonging to the Abrus
      precatorius plant. The child's gastrointestinal symptoms were consistent with
      reported cases of abrin poisoning, but the patient also had an isolated and
      significantly elevated alkaline phosphatase, with testing unable to reveal the
      responsible pathological process. CONCLUSIONS: To reduce morbidity and possible
      mortality, parents and pediatricians alike should be conscious of the danger the
      Abrus precatorius seed poses to the pediatric population. Children are at a
      greater risk of ingesting these seeds due to their colorful appearance, and the
      consequences could be fatal. Through this case report we hope to raise public
      awareness regarding this toxin. This includes the management of known cases, as
      well as the possibility of encountering an isolated elevated alkaline phosphatase
      level as a laboratory finding if ingestion occurs.

PMID- 25754814
TI  - Targeting the heat shock response in combination with radiotherapy: Sensitizing
      cancer cells to irradiation-induced cell death and heating up their
      immunogenicity.
AB  - Radiotherapy represents an essential treatment option for the majority of cancer
      patients in different stages of their disease. Physical achievements of the
      recent years led to the implementation of high precision treatment planning
      procedures, and image-guided dose delivery is current state of the art. Yet,
      radiotherapy still faces several limitations with cancer intrinsic
      radioresistance being a key driver of therapeutic failure. Accordingly, the
      mechanisms orchestrating radioresistance and their therapeutic targeting by
      combined modality approaches are in the center of attention of numerous radiation
      oncologists. In the present review, we summarize and discuss therapeutic
      approaches that exploit the heat shock response, either by hyperthermia or by
      pharmacological heat shock protein inhibition, in combination with radiotherapy.
      These strategies appear particularly promising, since they sensitize cancer cells
      to irradiation-induced cell death and at the same time have proven the potential
      to promote systemic anti-tumor immune mechanisms, which may target not only
      locally surviving tumor cells, but also distant out-of-field metastases. 

PMID- 25754816
TI  - The effect of ionizing radiation on regulatory T cells in health and disease.
AB  - Treg cells are key elements of the immune system which are responsible for the
      immune suppressive phenotype of cancer patients. Interaction of Treg cells with
      conventional anticancer therapies might fundamentally influence cancer therapy
      response rates. Radiotherapy, apart from its direct tumor cell killing potential,
      has a contradictory effect on the antitumor immune response: it augments certain
      immune parameters, while it depresses others. Treg cells are intrinsically
      radioresistant due to reduced apoptosis and increased proliferation, which leads
      to their systemic and/or intratumoral enrichment. While physiologically Treg
      suppression is not enhanced by irradiation, this is not the case in a tumorous
      environment, where Tregs acquire a highly suppressive phenotype, which is further
      increased by radiotherapy. This is the reason why the interest for combined
      radiotherapy and immunotherapy approaches focusing on the abrogation of Treg
      suppression has increased in cancer therapy in the last few years. Here we
      summarize the basic mechanisms of Treg radiation response both in healthy and
      cancerous environments and discuss Treg-targeted pre-clinical and clinical
      immunotherapy approaches used in combination with radiotherapy. Finally, the
      discrepant findings regarding the predictive value of Tregs in therapy response
      are also reviewed. 

PMID- 25754815
TI  - Ultrasound-mediated destruction of paclitaxel and oxygen loaded lipid
      microbubbles for combination therapy in ovarian cancer xenografts.
AB  - We have synthesized multifunctional oxygen and paclitaxel loaded microbubbles
      (OPLMBs) for ultrasound mediated delivery of combination therapy in an ovarian
      cancer xenograft model. In comparison with other therapeutic options, intravenous
      injection of OPLMBs followed by ultrasound mediation yielded a superior
      therapeutic outcome. Immunohistochemical analyses of the dissected tumor tissue
      confirmed the increased tumor apoptosis and the reduced VEGF expression after
      treatment. Western Blot tests further confirmed the decreased expressions of HIF
      1alpha and P-gp. Our experiment suggests that ultrasound mediation of OPLMBs may
      provide a promising drug delivery strategy for the combination treatment of
      ovarian cancer.

PMID- 25754817
TI  - miR-5100 promotes tumor growth in lung cancer by targeting Rab6.
AB  - Our previous study demonstrated that microRNA 5100 (miR-5100) is overexpressed in
      lung cancer tissues; however, the function of miR-5100 remained elusive. In this
      study, we demonstrate that miR-5100 is highly expressed in a wide variety of lung
      cancer tissues and lung cancer cell lines. Exogenous expression of miR-5100 in
      A549 and H1299 lung cancer cells enhanced proliferation and colony formation, and
      conversely, suppression of miR-5100 exhibited inhibitory effects. Furthermore, we
      demonstrate that miR-5100 promotes tumor growth in nude mice. These effects may
      result from the ability of miR-5100 to promote G1/S transition and downregulate
      cyclin D1 and cyclin-dependent kinases 2 (CDK2) expressions in lung cancer stable
      cells. Using a bioinformatics target prediction tool, we identified Rab6 as a
      potential target of miR-5100. Consistently, overexpression of miR-5100
      specifically reduced the expression of a luciferase reporter containing the
      predicted binding site from the 3'untranslated region (3'UTR) of Rab6 and
      decreased the accumulation of endogenous Rab6 in A549 and H1299 cells. Moreover,
      exogenous expression of Rab6 compromised the effects of miR-5100 on cell
      proliferation and colony formation. Our data suggest that miR-5100 promotes tumor
      growth by facilitating the G1/S transition and targeting Rab6.

PMID- 25754818
TI  - Long noncoding RNAs: novel players in colorectal cancer.
AB  - Colorectal cancer (CRC) is the most common type of cancer in the world. Despite
      its commonness, the underlying mechanism of CRC is not completely understood.
      Long noncoding RNAs (lncRNAs) have received increased attention with the
      development of whole genome and transcriptome sequencing technologies. Recent
      findings reveal that lncRNAs are implicated in serial steps of cancer
      development. These lncRNAs interact with DNA, RNA, protein molecules and/or their
      combinations, acting as an essential regulator in chromatin organization, and
      transcriptional and post-transcriptional regulation. In this review, we highlight
      recent findings of emerging roles for lncRNAs in CRC and discuss rapid
      translational lncRNA research for clinical application in diagnosis, prognosis
      and potential treatment.

PMID- 25754819
TI  - Faraday rotation and photoluminescence in heavily Tb(3+)-doped GeO2-B2O3-Al2O3
      Ga2O3 glasses for fiber-integrated magneto-optics.
AB  - We report on the magneto-optical (MO) properties of heavily Tb(3+)-doped GeO2
      B2O3-Al2O3-Ga2O3 glasses towards fiber-integrated paramagnetic MO devices. For a
      Tb(3+) ion concentration of up to 9.7 * 10(21) cm(-3), the reported glass
      exhibits an absolute negative Faraday rotation of ~120 rad/T/m at 632.8 nm. The
      optimum spectral ratio between Verdet constant and light transmittance over the
      spectral window of 400-1500 nm is found for a Tb(3+) concentration of ~6.5 *
      10(21) cm(-3). For this glass, the crystallization stability, expressed as the
      difference between glass transition temperature and onset temperature of melt
      crystallization exceeds 100 K, which is a prerequisite for fiber drawing. In
      addition, a high activation energy of crystallization is achieved at this
      composition. Optical absorption occurs in the NUV and blue spectral region,
      accompanied by Tb(3+) photoluminescence. In the heavily doped materials, a
      UV/blue-to-green photo-conversion gain of ~43% is achieved. The lifetime of
      photoluminescence is ~2.2 ms at a stimulated emission cross-section sigmaem of
      ~1.1 * 10(-21) cm(2) for ~ 5.0 * 10(21) cm(-3) Tb(3+). This results in an optical
      gain parameter sigmaem*tau of ~2.5 * 10(-24) cm(2)s, what could be of interest
      for implementation of a Tb(3+) fiber laser. 

PMID- 25754820
TI  - Melatonin is required for the circadian regulation of sleep.
AB  - Sleep is an evolutionarily conserved behavioral state whose regulation is poorly
      understood. A classical model posits that sleep is regulated by homeostatic and
      circadian mechanisms. Several factors have been implicated in mediating the
      homeostatic regulation of sleep, but molecules underlying the circadian mechanism
      are unknown. Here we use animals lacking melatonin due to mutation of
      arylalkylamine N-acetyltransferase 2 (aanat2) to show that melatonin is required
      for circadian regulation of sleep in zebrafish. Sleep is dramatically reduced at
      night in aanat2 mutants maintained in light/dark conditions, and the circadian
      regulation of sleep is abolished in free-running conditions. We find that
      melatonin promotes sleep downstream of the circadian clock as it is not required
      to initiate or maintain circadian rhythms. Additionally, we provide evidence that
      melatonin may induce sleep in part by promoting adenosine signaling, thus
      potentially linking circadian and homeostatic control of sleep. 

PMID- 25754821
TI  - Subtype-specific regeneration of retinal ganglion cells following axotomy:
      effects of osteopontin and mTOR signaling.
AB  - In mammals, few retinal ganglion cells (RGCs) survive following axotomy, and even
      fewer regenerate axons. This could reflect differential extrinsic influences or
      the existence of subpopulations that vary in their responses to injury. We tested
      these alternatives by comparing responses of molecularly distinct subsets of
      mouse RGCs to axotomy. Survival rates varied dramatically among subtypes, with
      alpha-RGCs (alphaRGCs) surviving preferentially. Among survivors, alphaRGCs
      accounted for nearly all regeneration following downregulation of PTEN, which
      activates the mTOR pathway. alphaRGCs have uniquely high mTOR signaling levels
      among RGCs and also selectively express osteopontin (OPN) and receptors for the
      insulin-like growth factor 1 (IGF-1). Administration of OPN plus IGF-1 promotes
      regeneration as effectively as downregulation of PTEN; however, regeneration is
      still confined to alphaRGCs. Our results reveal dramatic subtype-specific
      differences in the ability of RGCs to survive and regenerate following injury,
      and they identify promising agents for promoting axonal regeneration. 

PMID- 25754822
TI  - Daam2-PIP5K is a regulatory pathway for Wnt signaling and therapeutic target for
      remyelination in the CNS.
AB  - Wnt signaling plays an essential role in developmental and regenerative
      myelination of the CNS; however, contributions of proximal regulators of the Wnt
      receptor complex to these processes remain undefined. To identify components of
      the Wnt pathway that regulate these processes, we applied a multifaceted
      discovery platform and found that Daam2-PIP5K comprise a novel pathway regulating
      Wnt signaling and myelination. Using dorsal patterning of the chick spinal cord
      we found that Daam2 promotes Wnt signaling and receptor complex formation through
      PIP5K-PIP2. Analysis of Daam2 function in oligodendrocytes (OLs) revealed that it
      suppresses OL differentiation during development, after white matter injury
      (WMI), and is expressed in human white matter lesions. These findings suggest a
      pharmacological strategy to inhibit Daam2-PIP5K function, application of which
      stimulates remyelination after WMI. Put together, our studies integrate
      information from multiple systems to identify a novel regulatory pathway for Wnt
      signaling and potential therapeutic target for WMI. 

PMID- 25754823
TI  - Collateral pathways from the ventromedial hypothalamus mediate defensive
      behaviors.
AB  - The ventromedial hypothalamus (VMH) was thought to be essential for coping with
      threat, although its circuit mechanism remains unclear. To investigate this, we
      optogenetically activated steroidogenic factor 1 (SF1)-expressing neurons in the
      dorsomedial and central parts of the VMH (VMHdm/c), and observed a range of
      context-dependent somatomotor and autonomic responses resembling animals' natural
      defensive behaviors. By activating independent pathways emanating from the
      VMHdm/c, we demonstrated that VMHdm/c projection to the dorsolateral
      periaqueductal gray (dlPAG) induces inflexible immobility, while the VMHdm/c to
      anterior hypothalamic nucleus (AHN) pathway promotes avoidance. Consistent with
      the behavior changes induced by VMH to AHN pathway activation, direct activation
      of the AHN elicited avoidance and escape jumping, but not immobility. Retrograde
      tracing studies revealed that nearly 50% of PAG-projecting VMHdm/c neurons send
      collateral projection to the AHN and vice versa. Thus, VMHdm/c neurons employ a
      one-to-many wiring configuration to orchestrate multiple aspects of defensive
      behaviors.

PMID- 25754824
TI  - Pentraxins coordinate excitatory synapse maturation and circuit integration of
      parvalbumin interneurons.
AB  - Circuit computation requires precision in the timing, extent, and synchrony of
      principal cell (PC) firing that is largely enforced by parvalbumin-expressing,
      fast-spiking interneurons (PVFSIs). To reliably coordinate network activity,
      PVFSIs exhibit specialized synaptic and membrane properties that promote
      efficient afferent recruitment such as expression of high-conductance, rapidly
      gating, GluA4-containing AMPA receptors (AMPARs). We found that PVFSIs upregulate
      GluA4 during the second postnatal week coincident with increases in the AMPAR
      clustering proteins NPTX2 and NPTXR. Moreover, GluA4 is dramatically reduced in
      NPTX2(-/-)/NPTXR(-/-) mice with consequent reductions in PVFSI AMPAR function.
      Early postnatal NPTX2(-/-)/NPTXR(-/-) mice exhibit delayed circuit maturation
      with a prolonged critical period permissive for giant depolarizing potentials.
      Juvenile NPTX2(-/-)/NPTXR(-/-) mice display reduced feedforward inhibition
      yielding a circuit deficient in rhythmogenesis and prone to epileptiform
      discharges. Our findings demonstrate an essential role for NPTXs in controlling
      network dynamics highlighting potential therapeutic targets for disorders with
      inhibition/excitation imbalances such as schizophrenia.

PMID- 25754825
TI  - Chronic stress induces anxiety via an amygdalar intracellular cascade that
      impairs endocannabinoid signaling.
AB  - Collapse of endocannabinoid (eCB) signaling in the amygdala contributes to stress
      induced anxiety, but the mechanisms of this effect remain unclear. eCB production
      is tied to the function of the glutamate receptor mGluR5, itself dependent on
      tyrosine phosphorylation. Herein, we identify a novel pathway linking eCB
      regulation of anxiety through phosphorylation of mGluR5. Mice lacking LMO4, an
      endogenous inhibitor of the tyrosine phosphatase PTP1B, display reduced mGluR5
      phosphorylation, eCB signaling, and profound anxiety that is reversed by genetic
      or pharmacological suppression of amygdalar PTP1B. Chronically stressed mice
      exhibited elevated plasma corticosterone, decreased LMO4 palmitoylation, elevated
      PTP1B activity, reduced amygdalar eCB levels, and anxiety behaviors that were
      restored by PTP1B inhibition or by glucocorticoid receptor antagonism.
      Consistently, corticosterone decreased palmitoylation of LMO4 and its inhibition
      of PTP1B in neuronal cells. Collectively, these data reveal a stress-responsive
      corticosterone-LMO4-PTP1B-mGluR5 cascade that impairs amygdalar eCB signaling and
      contributes to the development of anxiety.

PMID- 25754826
TI  - Gamma rhythms link prefrontal interneuron dysfunction with cognitive
      inflexibility in Dlx5/6(+/-) mice.
AB  - Abnormalities in GABAergic interneurons, particularly fast-spiking interneurons
      (FSINs) that generate gamma (gamma; ~30-120 Hz) oscillations, are hypothesized to
      disrupt prefrontal cortex (PFC)-dependent cognition in schizophrenia. Although
      gamma rhythms are abnormal in schizophrenia, it remains unclear whether they
      directly influence cognition. Mechanisms underlying schizophrenia's typical post
      adolescent onset also remain elusive. We addressed these issues using mice
      heterozygous for Dlx5/6, which regulate GABAergic interneuron development. In
      Dlx5/6(+/-) mice, FSINs become abnormal following adolescence, coinciding with
      the onset of cognitive inflexibility and deficient task-evoked gamma
      oscillations. Inhibiting PFC interneurons in control mice reproduced these
      deficits, whereas stimulating them at gamma-frequencies restored cognitive
      flexibility in adult Dlx5/6(+/-) mice. These pro-cognitive effects were frequency
      specific and persistent. These findings elucidate a mechanism whereby abnormal
      FSIN development may contribute to the post-adolescent onset of schizophrenia
      endophenotypes. Furthermore, they demonstrate a causal, potentially therapeutic,
      role for PFC interneuron-driven gamma oscillations in cognitive domains at the
      core of schizophrenia.

PMID- 25754828
TI  - A new technique of extreme lateral positioning for laparoscopic splenic flexure
      mobilization.
AB  - AIM: This aim of this study was to describe a novel positioning technique that
      assists in the expeditious mobilization of the splenic flexure without the need
      for redraping or compromise of port placement. METHOD: A prospective case series
      was studied to evaluate the technique and its ability to facilitate splenic
      flexure mobilization. RESULTS: The technique was used in 12 patients. There were
      no adverse intra- or postoperative events. The median time (interquartile range)
      for laparoscopic splenic flexure mobilisation was 10 (9-11.25). CONCLUSION: This
      novel positioning technique is safe and feasible. We include a detailed video
      that describes and demonstrates the requisites for its safe conduct. We also
      include intra-operative footage demonstrating the benefits of the patient's
      position.

PMID- 25754829
TI  - Chronic urticaria due to autoreactivity to progesterone.
AB  - A 23-year-old, regularly menstruating woman presented with recurrent urticarial
      eruptions, which occurred premenstrually. A skin prick test was positive for
      progesterone, but the urticaria was unresponsive to standard treatments. The
      patient was treated with goserelin (Zoladex), which suppressed her menstrual
      cycle, leading to the resolution of her symptoms. Subsequent flares were
      controlled by further goserelin injections, and the urticaria is currently in
      remission. However, the risks of inducing menopause artificially are significant,
      and alternative long-term solutions may need to be considered in the event of a
      relapse. 

PMID- 25754827
TI  - A genome-wide screen identifies PAPP-AA-mediated IGFR signaling as a novel
      regulator of habituation learning.
AB  - Habituation represents a fundamental form of learning, yet the underlying
      molecular genetic mechanisms are not well defined. Here we report on a genome
      wide genetic screen, coupled with whole-genome sequencing, that identified 14
      zebrafish startle habituation mutants including mutants of the vertebrate
      specific gene pregnancy-associated plasma protein-aa (pappaa). PAPP-AA encodes an
      extracellular metalloprotease known to increase IGF bioavailability, thereby
      enhancing IGF receptor signaling. We find that pappaa is expressed by startle
      circuit neurons, and expression of wild-type but not a metalloprotease-inactive
      version of pappaa restores habituation in pappaa mutants. Furthermore, acutely
      inhibiting IGF1R function in wild-type reduces habituation, while activation of
      IGF1R downstream effectors in pappaa mutants restores habituation, demonstrating
      that pappaa promotes learning by acutely and locally increasing IGF
      bioavailability. In sum, our results define the first functional gene set for
      habituation learning in a vertebrate and identify PAPPAA-regulated IGF signaling
      as a novel mechanism regulating habituation learning. 

PMID- 25754830
TI  - A passive function of mitochondrial ATP synthase: target for tumor killer HAMLET.

PMID- 25754831
TI  - If nurses nurse, why don't doctors doctor?

PMID- 25754832
TI  - Influence of platelet clumps on platelet function analyser (PFA)-200(r) testing.

PMID- 25754833
TI  - Compassionate Care: Student nurses' learning through reflection and the use of
      story.
AB  - INTRODUCTION: Current concern in health care about delivering care that is
      compassionate has important implications for how compassion is taught and made
      explicit in nurse education curricula. This paper will describe the use of
      stories within the curricula to enhance knowledge and skills in compassionate
      caring. METHODOLOGY: The Leadership in Compassionate Care Programme (LCCP) was a
      3-year action research project that sought to capture what compassionate care
      means within practice and utilise this learning within education. Stories
      gathered within clinical practice were used to stimulate reflective learning as
      part of a nursing module that teaches recognition of acute illness and
      deterioration at Edinburgh Napier University. Students listened to stories which
      included experiences of staff, students, patients and relatives and related these
      to their own experiences in practice. In this paper, examples from the online
      discussions are discussed with reference to one of six themes that emerged from
      the LCCP, that of caring conversations. FINDINGS: The discussions suggest that
      reflective learning and the use of stories about the experience of giving and
      receiving care can contribute to the development of the knowledge, skill and
      confidence that enable student nurses to provide compassionate relationship
      centred care within practice. CONCLUSIONS: Reflective learning can be a valuable
      strategy for students to ponder new knowledge and allow predetermined ideas to be
      challenged. Stories can initiate this process and help student nurses to
      understand not only the needs of others, but their own expectations and values,
      which in turn can inform how they plan and deliver person centred compassionate
      care.

PMID- 25754834
TI  - Seasonal plasticity in the peptide neuronal systems: potential roles of
      gonadotrophin-releasing hormone, gonadotrophin-inhibiting hormone, neuropeptide Y
      and vasoactive intestinal peptide in the regulation of the reproductive axis in
      subtropical Indian weaver birds.
AB  - Two experiments examined the expression of gonadotrophin-releasing and inhibiting
      hormones (GnRH-I, GnRH-II and GnIH), neuropeptide Y (NPY) and vasoactive
      intestinal peptide (VIP) in subtropical Indian weaver birds, which demonstrate
      relative photorefractoriness. Experiment 1 measured peptide expression levels in
      the form of immunoreactive (-IR) cells, percentage cell area and cell optical
      density in the preoptic area (GnRH-I), midbrain (GnRH-II), paraventricular
      nucleus (GnIH), mediobasal hypothalamus [dorsomedial hypothalamus (DMH),
      infundibular complex (INc), NPY and VIP] and lateral septal organ (VIP) during
      the progressive, breeding, regressive and nonbreeding phases of the annual
      reproductive cycle. GnRH-I was decreased in the nonbreeding and VIP was increased
      in INc in the breeding and regressive states. GnRH-II and NPY levels did not
      differ between the testicular phases. Double-labelled immunohistochemistry (IHC)
      revealed a close association between the GnRH/GnIH, GnRH/NPY, GnRH/VIP and
      GnIH/NPY peptide systems, implicating them interacting and playing roles in the
      reproductive regulation in weaver birds. Experiment 2 further measured these
      peptide levels in the middle of day and night in weaver birds that were
      maintained under short days (8 : 16 h light /dark cycle; photosensitive), exposed
      to ten long days (16 : 8 h light /dark cycle; photostimulated) or maintained for
      approximately 2 years on a 16 : 8 h light /dark cycle (photorefractory).
      Reproductively immature testes in these groups precluded the possible effect of
      an enhanced gonadal feedback on the hypothalamic peptide expression. There were
      group differences in the GnRH-I (not GnRH-II), GnIH, NPY and VIP
      immunoreactivity, albeit with variations in immunoreactivity measures in the
      present study. These results, which are consistent with those reported in birds
      with relative photorefractoriness, show the distribution and possibly a complex
      interaction of key neuropeptides in the regulation of the annual reproductive
      cycle in Indian weaver birds.

PMID- 25754835
TI  - Analysis of non-synonymous SNPs of the porcine SERPINA6 gene as potential causal
      variants for a QTL affecting plasma cortisol levels on SSC7.
AB  - Recently, the SERPINA6 gene encoding corticosteroid-binding globulin (CBG) has
      been proposed as a candidate gene for a quantitative trait locus (QTL) affecting
      cortisol level on pig chromosome 7. The QTL was repeatedly detected in different
      lines, including a Pietrain * (German Landrace * German Large White) cross (PiF1)
      and purebred German Landrace (LR). In this study, we investigated whether the
      known non-synonymous polymorphisms c.44G>T, c.622C>T, c.770C>T, c.793G>A,
      c.832G>A and c.919G>A of SERPINA6 are sufficient to explain the QTL in these two
      populations. Our investigations revealed that SNPs c.44G>T, c.622C>T, c.793G>A
      and c.919G>A are associated with cortisol level in PiF1 (P < 0.01). Haplotype
      analysis showed that these associations are largely attributable to differences
      between a major haplotype carrying SNPs c.793G>A and c.919G>A and a haplotype
      carrying SNPs c.44G>T and c.622C>T. Furthermore, some SNPs, particularly c.44G>T
      and c.622C>T and the carrier haplotype, showed association with meat quality
      traits including pH and conductivity (P < 0.05). In LR, the non-synonymous SNPs
      segregate at very low frequency (<5%) and/or show only weak association with
      cortisol level (SNPs c.832G>A and c.919G>A; P < 0.05). These findings suggest
      that the non-synonymous SNPs are not sufficient to explain the QTL across
      different breeds. Therefore, we examined whether the expression of SERPINA6 is
      affected by cis-regulatory polymorphisms in liver, the major organ for CBG
      production. We found allelic expression imbalance of SERPINA6, which suggests
      that its expression is indeed affected by genetic variation in cis-acting
      elements. This represents candidate causal variation for future studies of the
      molecular background of the QTL.

PMID- 25754836
TI  - International REgistry to assess medical Practice with lOngitudinal obseRvation
      for Treatment of Heart Failure (REPORT-HF): rationale for and design of a global
      registry.
AB  - AIMS: The clinical characteristics, initial presentation, management, and
      outcomes of patients hospitalized with new-onset (first diagnosis) heart failure
      (HF) or decompensation of chronic HF are poorly understood worldwide. REPORT-HF
      (International REgistry to assess medical Practice with lOngitudinal obseRvation
      for Treatment of Heart Failure) is a global, prospective, and observational study
      designed to characterize patient trajectories longitudinally during and following
      an index hospitalization for HF. METHODS: Data collection for the registry will
      be conducted at ~300 sites located in ~40 countries. Comprehensive data including
      demographics, clinical presentation, co-morbidities, treatment patterns, quality
      of life, in-hospital and post-discharge outcomes, and health utilization and
      costs will be collected. Enrolment of ~20 000 adult patients hospitalized with
      new-onset (first diagnosis) HF or decompensation of chronic HF over a 3-year
      period is planned with subsequent 3 years follow-up. PERSPECTIVE: The REPORT-HF
      registry will explore the clinical characteristics, management, and outcomes of
      HF worldwide. This global research programme may have implications for the
      formulation of public health policy and the design and conduct of international
      clinical trials.

PMID- 25754837
TI  - Pulse sequence programming in a dynamic visual environment: SequenceTree.
AB  - PURPOSE: To describe SequenceTree, an open source, integrated software
      environment for implementing MRI pulse sequences and, ideally, exporting them to
      actual MRI scanners. The software is a user-friendly alternative to vendor
      supplied pulse sequence design and editing tools and is suited for programmers
      and nonprogrammers alike. METHODS: The integrated user interface was programmed
      using the Qt4/C++ toolkit. As parameters and code are modified, the pulse
      sequence diagram is automatically updated within the user interface. Several
      aspects of pulse programming are handled automatically, allowing users to focus
      on higher-level aspects of sequence design. Sequences can be simulated using a
      built-in Bloch equation solver and then exported for use on a Siemens MRI
      scanner. Ideally, other types of scanners will be supported in the future.
      RESULTS: SequenceTree has been used for 8 years in our laboratory and elsewhere
      and has contributed to more than 50 peer-reviewed publications in areas such as
      cardiovascular imaging, solid state and nonproton NMR, MR elastography, and high
      resolution structural imaging. CONCLUSION: SequenceTree is an innovative, open
      source, visual pulse sequence environment for MRI combining simplicity with
      flexibility and is ideal both for advanced users and users with limited
      programming experience.

PMID- 25754838
TI  - Biological relevance of Hsp90-binding immunophilins in cancer development and
      treatment.
AB  - Immunophilins are a family of intracellular receptors for immunosuppressive
      drugs. Those immunophilins that are related to immunosuppression are the smallest
      proteins of the family, i.e., FKBP12 and CyPA, whereas the other members of the
      family have higher molecular weight because the show additional domains to the
      drug-binding site. Among these extra domains, the TPR-domain is perhaps the most
      relevant because it permits the interaction of high molecular weight
      immunophilins with the 90-kDa heat-shock protein, Hsp90. This essential molecular
      chaperone regulates the biological function of several protein-kinases,
      oncogenes, protein phosphatases, transcription factors and cofactors . Hsp90
      binding immunophilins where first characterized due to their association with
      steroid receptors. They regulate the cytoplasmic transport and the subcellular
      localization of these and other Hsp90 client proteins, as well as transcriptional
      activity, cell proliferation, cell differentiation and apoptosis. Hsp90-binding
      immunophilins are frequently overexpressed in several types of cancers and play a
      key role in cell survival. In this article we analyze the most important
      biological actions of the best characterized Hsp90-binding immunophilins in both
      steroid receptor function and cancer development and discuss the potential use of
      these immunophilins for therapeutic purposes as potential targets of specific
      small molecules. 

PMID- 25754839
TI  - bFGF and Activin A function to promote survival and proliferation of single iPS
      cells in conditioned half-exchange mTeSR1 medium.
AB  - Human induced pluripotent stem (iPS) cells can be well maintained by clonal
      growth. The pluripotent growth of single iPS cells is limited by low survival. To
      facilitate robust single iPS cells cultured in vitro, half-exchange mTeSR1 medium
      (HM), whole-exchange medium (WM) and iPS cell-derived conditioned medium (iPS-CM)
      culture were used. The effects of bFGF and Activin A on the growth of single iPS
      cells were explored. The dissociation and propagation of single iPS cells also
      included Accutase enzymatic isolation, Rho-associated protein kinase (ROCK)
      inhibitor Y27632 protection and high-density single-cell seeding (1 * 10(6)
      cells/well). CCK-8 assays demonstrated that the viability of clonal iPS cells in
      mTeSR1 medium and single iPS cells in HM, iPS-CM or WM supplemented with 100
      ng/ml bFGF and 10 ng/ml Activin A was significantly higher than that in WM.
      Annexin v and propidium iodide (PI) assay, Calcein AM and EthD-III double
      staining also confirmed the similar results. ELISA assays showed that the levels
      of bFGF and Activin A of single iPS cells in HM and iPS-CM were higher than
      single iPS cells in WM. Meanwhile, Reverse Transcription-Polymerase Chain
      Reaction (RT-PCR), quantitative Polymerase Chain Reaction (qPCR), Western
      Blotting (WB), Immunofluorescence (IF) and karyotype analysis revealed that HM
      culture was able to maintain undifferentiated markers of Nanog, Klf4, Sox2, Oct4,
      and did not affect the karyotype of iPS cells. Undifferentiated single iPS cells
      in HM displayed homogenized growth. These findings demonstrate that bFGF and
      Activin A are important for the survival and growth of single iPS cells. HM
      culture system combined Accutase, Y27632 and high-density single-cell seeding can
      facilitate short-term growth of single iPS cells in vitro. 

PMID- 25754840
TI  - Influenza A virus plasticity-A temporal analysis of species-associated genomic
      signatures.
AB  - BACKGROUND/PURPOSE: An influenza A pandemic occurred in 2009-2010. A novel H1N1
      virus (hereafter H1N1pdm) was responsible for this outbreak. H1N1pdm viruses have
      been largely seen in recent human influenza A viruses. This virus was descended
      from a triple-reassorted swine virus consisting of human, avian, and swine
      origins. As a result, the previously established species-associated signatures
      could be in jeopardy. METHODS: We analyzed all influenza A sequences in the past
      5 years after the inclusion of H1N1pdm into human viruses since 2009, and
      examined how human signatures may lose their distinctness by mixing with avian
      residues that H1N1pdm have brought in. In particular, we compared how those
      signatures were changed/shifted in the past 5 years for human-isolated avian
      influenza A viruses and discussed their implications. RESULTS: Only eight out of
      47 signatures remained human-like for human influenza A viruses in the past 5
      years. They are PB2 271A; PB1 336I; PA 356R and 409N; NP 33I, 305K, and 357K; and
      NS1 227R. Although most avian-like residues were preserved in human-isolated
      avian influenza A viruses, a number of them were found to have become or on the
      verge of becoming human-like, including PB2 627, PA 100, 356, 404, 409, NP 33,
      61, 305, 357, M2 20, and NS1 81. CONCLUSION: Analyzing how species-associated
      signatures are becoming human-like in human-isolated avian influenza A viruses
      helps in assessing their potential to go pandemic as well as providing insights
      into host adaptation.

PMID- 25754841
TI  - The clinical course of pain and function in older adults with a new primary care
      visit for back pain.
AB  - OBJECTIVES: To report the clinical course of older adults presenting for a new
      primary care visit for back pain, no healthcare visit for back pain within the
      prior 6 months, by describing pain intensity, disability, pain interference, and
      resolution of back pain over 12 months. DESIGN: Prospective inception cohort
      study. SETTING: Primary care settings of three integrated healthcare systems in
      the United States that participated in the Back pain Outcomes using Longitudinal
      Data (BOLD) registry. PARTICIPANTS: Five thousand two hundred eleven (99.5%) of
      the 5,239 adults aged 65 and older who had reached their 12-month follow-up date.
      MEASUREMENTS: Baseline demographic characteristics, EQ-5D score, duration of back
      pain, expectation for recovery, depression, and anxiety. Participant-reported
      outcomes of back-related disability (Roland Morris Disability Questionnaire),
      numerical pain rating scale, pain interference, and resolution of back pain were
      collected at baseline and 3, 6, and 12 months. RESULTS: Most improvement occurred
      within the first 3 months. The number and proportion with 30% improvement in back
      pain increased from 1,950 (42.3%) at 3 months to 1,994 (44.8%) by 12 months, and
      1,331 (28.8%) and 1,576 (35.4%) had 30% improvement in disability at 3 and 12
      months. Only 23.0% reported that their back pain had resolved at 12 months.
      Improvements in disability and interference with activity over 12 months differed
      according to age, duration of back pain, symptoms of depression and anxiety, and
      expectation for recovery. CONCLUSION: The majority of older adults in primary
      care practice settings presenting with a new visit for back pain have persistent
      symptoms, disability, and interference over 12 months of follow-up. Future
      research is needed to identify risk factors for persistent symptoms and effective
      interventions.

PMID- 25754843
TI  - Switched capacitor charge pump used for low-distortion imaging in atomic force
      microscope.
AB  - The switched capacitor charge pump (SCCP) is an effective method of linearizing
      charges on piezoelectric actuators and therefore constitute a significant
      approach to nano-positioning. In this work, it was for the first time implemented
      in an atomic force microscope for low-distortion imaging. Experimental results
      showed that the image quality was improved evidently under the SCCP drive
      compared with that under traditional linear voltage drive.

PMID- 25754842
TI  - TLR3/TRIF signalling pathway regulates IL-32 and IFN-beta secretion through
      activation of RIP-1 and TRAF in the human cornea.
AB  - Toll-like receptor-3 (TLR3) and RNA helicase retinoic-acid-inducible protein-1
      (RIG-I) serve as cytoplasmic sensors for viral RNA components. In this study, we
      investigated how the TLR3 and RIG-I signalling pathway was stimulated by viral
      infection to produce interleukin (IL)-32-mediated pro-inflammatory cytokines and
      type I interferon in the corneal epithelium using Epstein-Barr virus (EBV)
      infected human cornea epithelial cells (HCECs/EBV) as a model of viral keratitis.
      Increased TLR3 and RIG-I that are responded to EBV-encoded RNA 1 and 2 (EBER1 and
      EBER2) induced the secretion of IL-32-mediated pro-inflammatory cytokines and IFN
      beta through up-regulation of TRIF/TRAF family proteins or RIP-1. TRIF silencing
      or TLR3 inhibitors more efficiently inhibited sequential phosphorylation of TAK1,
      TBK1, NF-kappaB and IRFs to produce pro-inflammatory cytokines and IFN-beta than
      RIG-I-siRNA transfection in HCECs/EBV. Blockade of RIP-1, which connects the TLR3
      and RIG-I pathways, significantly blocked the TLR3/TRIF-mediated and RIG-I
      mediated pro-inflammatory cytokines and IFN-beta production in HCECs/EBV. These
      findings demonstrate that TLR3/TRIF-dependent signalling pathway against viral
      RNA might be a main target to control inflammation and anti-viral responses in
      the ocular surface. 

PMID- 25754844
TI  - Laparoscopic gastropexy relieves symptoms of obstructed gastric volvulus in
      highoperative risk patients.
AB  - BACKGROUND: Operative repair of obstructive gastric volvulus is challenging. In
      high-operative risk patients with obstructive gastric volvulus, we perform
      laparoscopic reduction of gastric volvulus and anterior abdominal wall sutured
      gastropexy. This case series reports our experience with this operation. METHODS:
      We reviewed the charts of all patients who presented with obstructive gastric
      volvulus and underwent laparoscopic gastropexy between 2007 and 2013. RESULTS:
      Eleven patients underwent laparoscopic gastropexy. Median age was 83 years (50 to
      92). Six patients presented with chronic obstruction; 5 presented with acute
      obstruction. Median postoperative hospitalization was 2 days (1 to 39). Two
      patients required reoperation for displaced gastrostomy tubes. At median follow
      up of 3 months (2 weeks to 57 months), all patients remained free of gastric
      obstructive symptoms and recurrent episodes of volvulus. Only 1 patient received
      nutrition via gastrostomy tube. CONCLUSIONS: Laparoscopic gastropexy can treat
      obstructed gastric volvulus in highoperative risk patients. Because of associated
      morbidity, gastrostomy tubes should be placed selectively.

PMID- 25754845
TI  - The influence of mechanical bowel preparation on long-term survival in patients
      surgically treated for colorectal cancer.
AB  - BACKGROUND: In this study, we evaluated long-term survival in patients treated
      with and without mechanical bowel preparation (MBP) before colorectal surgery for
      cancer. METHODS: Long-term outcome of patients of 2 main participating hospitals
      in a prior multicenter randomized trial comparing clinical outcome of MBP versus
      no MBP was reviewed. Primary endpoint was cancer-related mortality and secondary
      endpoint was all-cause mortality. RESULTS: A total of 382 patients underwent
      potentially curative surgery for colorectal cancer. One hundred seventy-seven
      (46%) patients were treated with MBP and 205 (54%) were not before surgery.
      Median follow-up was 7.6 years (mean 6.6, range .01 to 12.73). There was no
      significant difference in both cancer-related mortality and all-cause mortality
      in patients treated with MBP and without MBP (P = .76 and P = .36, respectively).
      Multivariate analysis, taking account of age, sex, AJCC cancer stage, and ASA
      classification, also showed no survival difference. CONCLUSIONS: Our results
      indicate that MBP does not seem to influence long-term survival in patients
      surgically treated for colorectal cancer.

PMID- 25754846
TI  - Results from a novel modification to the ligation intersphincteric fistula tract.
AB  - BACKGROUND: The ligation of intersphincteric fistula tract (LIFT) procedure for
      trans-sphincteric fistula-in-ano has been studied with variable success rates
      compared with initial reports. Failures occur mostly in the intersphincteric
      wound. Recently, we proposed a modification to LIFT, unroofing the fistula from
      internal opening to intersphincteric groove, ligating the fistula tract, but
      preserving the external sphincter. METHODS: This retrospective review assesses
      outcomes of patients undergoing the modified LIFT for trans-sphincteric fistulae.
      RESULTS: Sixty-six modified LIFT procedures were performed. The main cohort
      consisted of 56 patients, predominantly men (76.7%). Median operative time was 16
      minutes. Median follow-up was 20.98 weeks. Overall cure rate was 71.42%, with a
      recurrence rate of 5.35% and fistula persistence in 16.07%. There was no
      persistent fecal incontinence. CONCLUSION: Modified LIFT is a safe procedure that
      is easily performed, has short operative time, eliminates the intersphincteric
      space, and has cure rates equal to or better than the original LIFT.

PMID- 25754847
TI  - Nematicidal activity of allyl bromide and dibromo(nitro)methane under laboratory
      conditions.
AB  - BACKGROUND: Restrictions on soil fumigants are prompting the development of new
      compounds for controlling nematodes, other soilborne pathogens and weeds. We
      evaluated the nematicidal activity of five bromine compounds against Meloidogyne
      javanica in vitro, and tested the two most effective ones against Pratylenchus
      penetrans and Xiphinema index in vitro and in soil. RESULTS: Only allyl bromide
      and dibromo(nitro)methane showed nematicidal activity against M. javanica
      juveniles in vitro at <320 mg L(-1) . Allyl bromide killed M. javanica and P.
      penetrans at 20 mg L(-1), and X. index at 10 mg L(-1), whereas 320 mg
      dibromo(nitro)methane L(-1) was required to kill P. penetrans. Allyl bromide also
      showed higher nematicidal activity than dibromo(nitro)methane against M. javanica
      and P. penetrans in soil. Allyl bromide at 40 and 20 mg L(-1) soil eliminated
      root galls and nematode eggs on tomato roots grown in M. javanica-inoculated
      loess and sandy soils respectively, showing higher nematicidal activity than 1,3
      dichloropropene. No P. penetrans were recovered from soil treated with 80 mg
      allyl bromide L(-1) soil or 320 mg dibromo(nitro)methane L(-1) soil. CONCLUSION:
      Allyl bromide showed high nematicidal activity against all three nematode
      species, and nematicidal activity of dibromo(nitro)methane was discovered. These
      compounds could serve as new fumigation nematicides, pending further experiments.

PMID- 25754848
TI  - Hiccups and amniotic fluid regulation in early pregnancy.
AB  - Hiccups are an unexplained phenomenon and a subject of medical curiosity. They
      arise through a reflex arc with central control at the level of the medulla, and
      their primary physiological effect is the generation of negative intra-thoracic
      pressure. This paper presents the hypothesis that hiccups serve a purpose during
      the first half of gestation, when they are most prevalent; namely, that they
      promote amniotic fluid influx to the primitive gut, allowing fluid to be
      transferred to the foetal and then maternal vasculature. Furthermore, hiccups
      could be provoked by increasing amniotic fluid volume and pressure, and act in a
      regulatory capacity. This hypothesis could be tested by studying foetal movements
      in the first half of gestation, and assessing whether there is correlation with
      amniotic fluid flux in the developing gut. Ascertaining whether hiccups increase
      in frequency with increasing amniotic fluid volume would provide evidence for or
      against a regulatory function. 

PMID- 25754849
TI  - Lumboperitoneal shunt for the treatment of leptomeningeal metastasis.
AB  - Leptomeningeal metastasis (LM) is thought to be a devastating and increasingly
      frequent neurological complication of cancer characterized by infiltration of
      malignant cells into the leptomeninges and the subarachnoid space. Intracranial
      hypertension and hydrocephalus are observed in about half of patients with LM.
      They are responsible for rapidly declining neurological status and eventual poor
      outcome in many patients with LM. Impediment of CSF circulation is considered the
      pathophysiological basis of increased intracranial pressure and hydrocephalus
      related to LM, which makes ventriculoperitoneal shunt (VP shunt) an acceptable
      palliative approach for LM now. It is noteworthy that LM generally causes
      communicating hydrocephalus. Lumboperitoneal shunt (LP shunt) has been
      demonstrated to be effective in the treatment of communicating hydrocephalus
      secondary to hemorrhage or infection, idiopathic intracranial hypertension and
      normal pressure hydrocephalus. And LP shunt has several advantages over VP shunt.
      Therefore we hypothesize that LP shunt can be used in the treatment of
      intracranial hypertension and hydrocephalus related to LM and should be given
      greater priority over VP shunt. 

PMID- 25754850
TI  - Is the EuroSCORE II best suited for reoperative risk estimation in patients with
      structural deterioration of aortic bioprostheses?
AB  - BACKGROUND: Operative risk prediction systems (logistic EuroSCORE I, EuroSCORE II
      and STS Score) are employed together with multidisciplinary discussion to
      contraindicate conventional surgery in patients with valvular heart disease and
      propose the employment of alternative transcatheter procedures. The EuroSCORE I
      has been reported to underperform in these circumstances; we hypothesize that the
      EuroSCORE II is best suited for the stratification of risk in patients with
      structural deterioration (SVD) of valvular bioprostheses and potential candidates
      to the Valve-in-Valve procedure (deployment of a transcatheter valve within a
      failing valvular bioprosthesis). METHODS AND EVALUATION OF THE HYPOTHESIS: A
      multi-institutional collaboration is required to fully address such hypothesis.
      Therefore, we performed a preliminary validation study by retrieval of the
      complete records of 81 patients undergoing reoperative aortic valve replacement
      for preoperative diagnosis of bioprosthetic SVD at our Institution. Logistic
      EuroSCORE I, EuroSCORE II and STS Score were calculated by preoperatively
      available data. Faced to an observed reoperative mortality of 4.9%, average
      EuroSCORE I was 15.8%+/-13.4, EuroSCORE II was 7.3%+/-7.4 and the STS Score was
      15%+/-9.8. The three systems provided sufficient adequacy (Hosmer-Lemeshow
      p=0.847, p=0.999 and p=0.9948, respectively). Yet, the area under the ROC curve
      was significantly higher for the EuroSCORE II (0.9903) vs. the EuroSCORE I
      (0.8994) (p=0.044). The STS Score yielded an intermediate figure (0.9643). The
      odds ratios (logistic regression) were 1.079 for EuroSCORE I, 1.223 for the STS
      Score and 1.474 for EuroSCORE II. CONCLUSIONS: The three investigated algorithms
      showed reasonable calibration in the prediction of mortality for reoperative
      aortic valve replacement, but they evenly overestimated the observed mortality.
      The hypothesis that the EuroSCORE II is better suited for the selection of
      candidates to Valve-in-Valve implantation is worth of further multi-institutional
      investigations on the basis of our preliminary findings and due to the expanding
      role of transcatheter techniques.

PMID- 25754851
TI  - Functional morphology of the tubular genital organs in the female owl monkey
      (Aotus spp.).
AB  - BACKGROUND: Studies on reproductive morphology are important to understand the
      reproductive cycle of non-human primates. METHODS: This study describes the
      functional morphology of the adult female tubular genital organs in 41 Aotus
      (12.8 +/- 6.8 years old, ranging from 3 to 25 years), with respect to
      reproductive status and number of parturitions. RESULTS: In females with
      developing embryos, endometrial glands showed a higher secretion than other
      females, and the embryo implantation occupied this secretive endometrium. Changes
      in the thickening, number of layers, and keratinization in the vaginal epithelium
      suggest that vaginal cytology may be an indicator of the estrous cycle. Non
      pregnant multiparous females had a larger uterine body than nulliparous females.
      Number of parturitions and reproductive state had an impact on tubular genital
      organs in female owl monkeys. CONCLUSIONS: These results can be useful for the
      development of biotechnologies of reproduction and for improvement of the
      management of this species.

PMID- 25754852
TI  - Pathologic substrates of focal epilepsy influence the generation of high
      frequency oscillations.
AB  - OBJECTIVE: Although a clear correlation has been observed between high-frequency
      oscillations (HFOs) and the seizure-onset zone in distinct lesions, the role of
      the underlying pathologic substrates in the generation of HFOs is not well
      established. We aimed to investigate HFO correlates of different pathologic
      substrates in patients with drug-resistant epilepsy, and to examine the relation
      of HFOs with the anatomic location of the dysplastic lesion and surrounding
      tissue in patients with focal cortical dysplasia (FCD). METHODS: We studied
      consecutive patients with drug-resistant epilepsy who underwent intracranial
      electroencephalography (iEEG) investigations with depth electrodes at the
      Montreal Neurological Institute and Hospital, between November 2004 and May 2013.
      Inclusion criteria were the following: a focal lesion documented by magnetic
      resonance imaging (MRI); EEG recording at a 2,000 Hz sampling rate; and seizures
      starting from depth electrode contacts placed in lesion and perilesional tissue.
      RESULTS: Thirty-seven patients (13 FCD, 12 mesial temporal sclerosis, five
      cortical atrophy, three polymicrogyria, three nodular heterotopia, and one
      tuberous sclerosis) were included; 18 were women (median age 34). Ripples and
      fast ripples were found in all lesion types, except tuberous sclerosis, which
      showed no fast ripples. There was a significant difference in rates of ripples
      and fast ripples across different lesions (p < 0.001), with higher rates in FCD,
      mesial temporal sclerosis, and nodular heterotopia than in atrophy,
      polymicrogyria, and tuberous sclerosis. Regarding patients with FCD, HFOs rates
      differed significantly across the three types of tissue (lesional, perilesional,
      and nonlesional; p < 0.001), being higher within the borders of the MRI-visible
      dysplastic lesion, followed by the surrounding area, and rare in the remote
      cortex. SIGNIFICANCE: Our findings suggest that in patients who are all
      intractable, the HFO rates vary with different pathologies, and reflect different
      types of neuronal derangements. Our results also emphasize the potential
      usefulness of HFOs as an additional method to better define the extent of the
      epileptogenic dysplastic tissue in FCD.

PMID- 25754853
TI  - Retraction: Sclera-Choroid-RPE Transport of Eight beta-Blockers in Human, Bovine,
      Porcine, Rabbit, and Rat Models.

PMID- 25754854
TI  - Erratum. Mesothelial Cells: A Cellular Surrogate for Tissue Engineering of
      Corneal Endothelium.

PMID- 25754856
TI  - Six-minute walk distance in patients with chronic obstructive pulmonary disease:
      Which reference equations should we use?
AB  - The use of different 6-min walk distance (6MWD) reference equations probably
      results in different predicted 6MWD reference values. We wished to investigate
      the impact of several 6MWD reference equations for adults in patients with
      chronic obstructive pulmonary disease (COPD) and factors accountable for
      different 6MWD% predicted values. Twenty-two 6MWD reference equations were
      applied to a data set of 2757 patients with COPD. The predicted 6MWD reference
      value of Troosters and colleagues was used as the point of reference. Four out of
      21 remaining equations resulted in comparable 6MWD% predicted, 16 equations
      resulted in significantly higher 6MWD% predicted and 1 equation resulted in a
      significantly lower 6MWD% predicted. Similar differences in 6MWD% predicted were
      observed after stratification by sex. Body mass index and global initiative for
      chronic obstructive lung disease (GOLD) stage classification demonstrated varying
      results within and between the groups; 9 out of 21 equations resulted in
      comparable 6MWD% predicted in underweight patients but only 1 equation
      demonstrated comparable result in obese. Eight equations in GOLD I, whilst 5 out
      of 21 equations in GOLD IV resulted in comparable 6MWD% predicted. Existing 6MWD
      reference equations will give varying results. The choice of 6MWD reference
      equation should consider the consistency of 6-min walk test operating procedures
      and at least be specific for the country/region of origin. 

PMID- 25754857
TI  - A prospective study on the use of teledermatology in psychiatric patients with
      chronic skin diseases.
AB  - BACKGROUND: To compare the use of live interactive teledermatology versus
      conventional face-to-face consultation in long-term, institutionalised
      psychiatric patients with chronic skin diseases. METHODS: All institutionalised
      psychiatric patients at the Institute of Mental Health with follow-up
      appointments at the National Skin Centre were assessed for eligibility and
      invited to participate. Recruited patients were first seen by a dermatologist via
      videoconferencing, and then by another dermatologist in person, within 1 week.
      Clinical outcome measures were then assessed by a third independent
      dermatologist. The following outcome measures were assessed for each paired
      patient visit: inter-physician clinical assessment, diagnosis, management plan,
      adverse events and total patient turnaround time (PTAT) for each consultation.
      RESULTS: There were a total of 13 patients (mean age, 64.6 years; range 44-80)
      with 27 patient visits. All were male patients with chronic schizophrenia. The
      predominant skin condition was chronic eczema and its variants (62%), followed by
      cutaneous amyloidosis (23%) and psoriasis (15%). The level of complete and
      partial agreement between the teledermatology and face-to-face consultation was
      100% for history-taking and physical examination and 96% for the investigations,
      diagnosis, management plan and the treatment prescribed. The PTAT for
      teledermatology was 23 min, compared to 240 min for face-to-face consultations.
      No adverse events were reported. CONCLUSION: Teledermatology was as effective as
      face-to-face consultation and reduced the PTAT by 90%, resulting in increased
      patient convenience, operational efficiency and reduced manpower need. Our study
      supports the safe and cost-effective use of teledermatology for the follow-up of
      chronic skin conditions in psychiatric patients.

PMID- 25754855
TI  - Latest updates on antiretinal autoantibodies associated with vision loss and
      breast cancer.
AB  - Cancer-associated retinopathy (CAR) is an uncommon paraneoplastic disorder of the
      retina that is frequently associated with breast cancer in pre- and
      postmenopausal women older than 50 years. In this review, we will give an update
      on the current knowledge regarding the association of antiretinal autoantibodies
      with the breast-CAR syndrome. Women with breast cancer and visual indications of
      CAR have a significantly increased incidence of autoantibodies (AAbs) against
      retinal proteins when compared to healthy women. The onset of visual loss in
      association with antiretinal AAbs peaks 2 to 3 years after the clinical diagnosis
      of breast cancer. Differences in severity of symptoms between women with or
      without antiretinal AAbs are evident, revealing more unfavorable presentation in
      seropositive women. The incidence of CAR in breast cancer is likely to rise as
      the survival time of patients with breast cancer increases; consequently, a
      prediction of breast-CAR based on autoimmunity to individual retinal antigens, or
      to panels of antigens (signatures), is clinically important. 

PMID- 25754858
TI  - Characteristics of the developing human locomotor system: Similarities to other
      mammals.
AB  - Similarities in the development of locomotion between young children and other
      mammals are explored by reanalysis of data accrued over ~18 years. Supported
      stepping in children was tested on a treadmill. Although the time course of
      development is more protracted in humans compared to other mammals, the same
      trends are seen. For example, the duration of the stepping cycle shortens rapidly
      in the first 5 months of life. Hypermetric flexion of the hip and knee during
      stepping is seen in children <3 mo old. Stability of the locomotor rhythm both
      with respect to cycle duration within a limb and coupling between limbs improves
      slowly. Finally, coordination between the left and right legs can be manipulated
      with training, indicating experience-dependent learning at a young age. The
      possible reasons for these remarkably similar trends in development are explored
      as a function of maturational time tables for neural structures.

PMID- 25754859
TI  - Presence of Epsilon HCH Together with Four Other HCH Isomers in Drinking Water,
      Groundwater and Soil in a Former Lindane Production Site.
AB  - In the frame of a long-standing action of remediation of industrial soil and
      prevention of water pollution, a monitoring of the drinking water of the Italian
      town of Colleferro was performed by the ISS. The town has 22,000 inhabitants and
      is adjacent to a big industrial site where HCH was produced. Industrial wastes
      were buried in the site, eventually contaminating superficial aquifers, while a
      canal serving the industrial plant spread the contamination into the Sacco river
      and thence to the agricultural soil and to cow milk. The contamination of
      superficial aquifers engendered fears of pollution of the deep aquifers whence
      the town draws its drinking water. The results of the monitoring indicate that
      there is no risk for the population from consumption of the water. In one of the
      wells the epsilon-HCH was the main isomer reaching a concentration of 66 ng/L: so
      far the presence of this isomer in water was never reported. The paper also
      summarily reports the main features of soil and superficial groundwater pollution
      in the area and briefly describes the main actions taken by the authorities.

PMID- 25754860
TI  - Calibration and application of an automated seepage meter for monitoring water
      flow across the sediment-water interface.
AB  - The advective flow of sediment pore water is an important parameter for
      understanding natural geochemical processes within lake, river, wetland, and
      marine sediments and also for properly designing permeable remedial sediment caps
      placed over contaminated sediments. Automated heat pulse seepage meters can be
      used to measure the vertical component of sediment pore water flow (i.e.,
      vertical Darcy velocity); however, little information on meter calibration as a
      function of ambient water temperature exists in the literature. As a result, a
      method with associated equations for calibrating a heat pulse seepage meter as a
      function of ambient water temperature is fully described in this paper. Results
      of meter calibration over the temperature range 7.5 to 21.2  degrees C indicate
      that errors in accuracy are significant if proper temperature-dependence
      calibration is not performed. The proposed calibration method allows for
      temperature corrections to be made automatically in the field at any ambient
      water temperature. The significance of these corrections is discussed.

PMID- 25754861
TI  - Synthesis of 'head-to-tail' cyclized peptides on solid support using a chelating
      amide as new orthogonal protecting group.
AB  - The synthesis of 'head-to-tail' cyclized peptides requires orthogonal protecting
      groups. Herein, we report on the introduction of bis(2-pyridylmethyl)amine (Bpa)
      as a new protecting group for carboxylic functions in SPPS. The synthesis of the
      Bpa-protected aspartic acid was straightforward, and its utility was investigated
      under standard peptide synthesis conditions. The new protecting group was cleaved
      in a very mild way using Cu(OAc)2 and 2-(trimethylsilyl)ethanol as nucleophile in
      a microwave oven without affecting other groups. Hence, the new group is ideally
      suited for the synthesis of 'head-to-tail' cyclic peptides, as demonstrated for a
      cyclic pentapeptide and cyclic hexapeptides.

PMID- 25754862
TI  - Coexistence of metallic and insulating-like states in graphene.
AB  - Since graphene has been taken as the potential host material for next-generation
      electric devices, coexistence of high carrier mobility and an energy gap has the
      determining role in its real applications. However, in conventional methods of
      band-gap engineering, the energy gap and carrier mobility in graphene are seemed
      to be the two terminals of a seesaw, which limit its rapid development in
      electronic devices. Here we demonstrated the realization of insulating-like state
      in graphene without breaking Dirac cone. Using first-principles calculations, we
      found that ferroelectric substrate not only well reserves the Dirac fermions, but
      also induces pseudo-gap states in graphene. Calculated transport results clearly
      revealed that electrons cannot move along the ferroelectric direction. Thus, our
      work established a new concept of opening an energy gap in graphene without
      reducing the high mobility of carriers, which is a step towards manufacturing
      graphene-based devices. 

PMID- 25754863
TI  - Combining computational models, semantic annotations and simulation experiments
      in a graph database.
AB  - Model repositories such as the BioModels Database, the CellML Model Repository or
      JWS Online are frequently accessed to retrieve computational models of biological
      systems. However, their storage concepts support only restricted types of queries
      and not all data inside the repositories can be retrieved. In this article we
      present a storage concept that meets this challenge. It grounds on a graph
      database, reflects the models' structure, incorporates semantic annotations and
      simulation descriptions and ultimately connects different types of model-related
      data. The connections between heterogeneous model-related data and bio-ontologies
      enable efficient search via biological facts and grant access to new model
      features. The introduced concept notably improves the access of computational
      models and associated simulations in a model repository. This has positive
      effects on tasks such as model search, retrieval, ranking, matching and
      filtering. Furthermore, our work for the first time enables CellML- and Systems
      Biology Markup Language-encoded models to be effectively maintained in one
      database. We show how these models can be linked via annotations and queried.
      Database URL: https://sems.uni-rostock.de/projects/masymos/ 

PMID- 25754864
TI  - mycoCLAP, the database for characterized lignocellulose-active proteins of fungal
      origin: resource and text mining curation support.
AB  - Enzymes active on components of lignocellulosic biomass are used for industrial
      applications ranging from food processing to biofuels production. These include a
      diverse array of glycoside hydrolases, carbohydrate esterases, polysaccharide
      lyases and oxidoreductases. Fungi are prolific producers of these enzymes,
      spurring fungal genome sequencing efforts to identify and catalogue the genes
      that encode them. To facilitate the functional annotation of these genes,
      biochemical data on over 800 fungal lignocellulose-degrading enzymes have been
      collected from the literature and organized into the searchable database,
      mycoCLAP (http://mycoclap.fungalgenomics.ca). First implemented in 2011, and
      updated as described here, mycoCLAP is capable of ranking search results
      according to closest biochemically characterized homologues: this improves the
      quality of the annotation, and significantly decreases the time required to
      annotate novel sequences. The database is freely available to the scientific
      community, as are the open source applications based on natural language
      processing developed to support the manual curation of mycoCLAP. Database URL:
      http://mycoclap.fungalgenomics.ca. 

PMID- 25754865
TI  - Migraine and epilepsy: review of the literature.
AB  - Migraine and epilepsy are disorders that are common, paroxysmal, and chronic. In
      many ways they are clearly different diseases, yet there are some
      pathophysiological overlaps, and overlaps in clinical symptomatology,
      particularly with regard to visual and other sensory disturbances, pain, and
      alterations of consciousness. Epidemiological studies have revealed that the two
      diseases are comorbid in a number of individuals. Both are now recognized as
      originating from electrical disturbances in the brain, although their wider
      manifestations involve the recruitment of multiple pathogenic mechanisms. An
      initial excess of neuronal activity in migraine leads to cortical spreading
      depression and aura, with the subsequent recruitment of the trigeminal nucleus
      leading to central sensitization and pain. In epilepsy, neuronal overactivity
      leads to the recruitment of larger populations of neurons firing in a rhythmic
      manner that constitutes an epileptic seizure. Migraine aura and headaches may act
      as a trigger for epileptic seizures. Epilepsy is not infrequently accompanied by
      preictal, ictal, and postictal headaches that often have migrainous features.
      Genetic links are also apparent between the two disorders, and are particularly
      evident in the familial hemiplegic migraine syndromes where different mutations
      can produce either migraine, epilepsy, or both. Also, various medications are
      found to be effective for both migraine and epilepsy, again pointing to a
      commonality and overlap between the two disorders. 

PMID- 25754866
TI  - Do postal health surveys capture morbidity and mortality in respondents aged 65
      years and older? A register-based validation study.
AB  - AIMS: Non-response to population surveys is a common problem in epidemiological
      and public health research. Systematic non-response threatens the validity of
      results. Researchers rarely evaluate the magnitude of systematic non-response
      because of limited access to population data. This study explores how well
      morbidity and mortality in postal survey respondents aged 65 years and older
      represented that of the target population. METHODS: The 2010 Stockholm Public
      Health Survey and the Swedish Population Register were linked to the Cause of
      Death Register and the National Patient Register in Sweden. Differences were
      analysed between the response group and the corresponding population in
      mortality, hospital admission, days spent in hospital and number of diagnoses.
      Finally, data were weighted for non-response to see if this improved
      generalizability. RESULTS: Non-response increased with age, and this increase was
      more pronounced among women than men. Respondents were marginally less often
      admitted to hospital, hospitalized fewer days and had slightly fewer diagnoses
      than the population, in particular after age 80. Significantly fewer women died
      in the response group than in the population as a whole. In terms of mortality
      among men and in terms of hospitalizations for most age groups, the respondents
      represented the population fairly well. Non-response weighting adjustment did not
      improve generalizability. CONCLUSIONS: Postal questionnaires are likely to
      capture morbidity (hospitalization) among women and men aged 65-80 years old and
      mortality among men, while morbidity after age 80 and mortality in women are
      likely to be underestimated.

PMID- 25754867
TI  - Changes in alcohol consumption between 2009 and 2014 assessed with the AUDIT.
AB  - BACKGROUND: Alcohol habits in Sweden, assessed as sales and estimates of
      unrecorded consumption, have changed since joining the EU. Earlier studies using
      the Alcohol Use Disorders Identification Test (AUDIT) showed that reported
      consumption is consistent with sales data, which makes it possible to assess
      consumption according to sex and age. AIMS: This study reports the changes in
      alcohol habits between 2009 and 2014, a period starting a couple of years after
      Sweden joined the EU. METHOD: The AUDIT was sent to a random sample of the
      Swedish population aged between 17 and 80 years old. RESULTS: No statistically
      significant changes were shown in six age and sex groups. CONCLUSIONS: Alcohol
      habits have stabilised in Sweden but on a higher consumption level than before.

PMID- 25754868
TI  - Attitudes towards human papillomavirus vaccination among Arab ethnic minority in
      Denmark: A qualitative study.
AB  - BACKGROUND: Knowledge regarding the human papillomavirus (HPV) and HPV vaccine
      uptake among ethnic minorities is poorly explored in Denmark. The objective of
      this study was to explore attitudes and knowledge towards HPV vaccination among
      Arab mothers and their daughters. METHODS: Five Arabic-speaking focus groups with
      mothers of vaccine-eligible girls and three focus groups with daughters were
      conducted. The participants were recruited through different social clubs. A
      phenomenological approach was used to investigate attitudes and knowledge of HPV
      vaccination. Meaning condensation inspired by Amedeo Giorgi was used to analyse
      the transcribed material. RESULTS: A total of 23 women and 13 daughters were
      included in this study. The mothers' knowledge regarding HPV was limited to the
      fact that HPV can cause cervical cancer. Two focus groups mentioned that HPV is a
      sexually transmitted disease and none of the mothers knew that HPV also causes
      genital warts. Both mothers and daughters acknowledged that the daughters have
      deeper insight into health-related issues. A gap of knowledge between generations
      was identified, as mothers and daughters obtained health information from
      different sources: mothers used the Arabic TV channels as a source of knowledge
      and daughters had a range of sources, e.g. school, internet, and Western TV
      channels. The consequence of these differences in obtaining knowledge is that
      mothers and daughters lack a common language to discuss health issues. Mothers
      were influenced by Arabic society, while daughters had created a hybrid of Arabic
      and Danish. Each generation had its own reasons for accepting the vaccine. The
      level of HPV knowledge and awareness did not affect their uptake decision in that
      all the participating mothers had accepted the vaccine for their daughters.
      CONCLUSIONS: Educational programs should target both mothers and daughters
      because mothers have an inadequate knowledge about HPV. This is likely to bridge
      the gap of knowledge between mothers and daughters, which constitutes a barrier
      between the generations.

PMID- 25754869
TI  - How fast-growing bacteria robustly tune their ribosome concentration to
      approximate growth-rate maximization.
AB  - Maximization of growth rate is an important fitness strategy for bacteria.
      Bacteria can achieve this by expressing proteins at optimal concentrations, such
      that resources are not wasted. This is exemplified for Escherichia coli by the
      increase of its ribosomal protein-fraction with growth rate, which precisely
      matches the increased protein synthesis demand. These findings and others have
      led to the hypothesis that E. coli aims to maximize its growth rate in
      environments that support growth. However, what kind of regulatory strategy is
      required for a robust, optimal adjustment of the ribosome concentration to the
      prevailing condition is still an open question. In the present study, we analyze
      the ppGpp-controlled mechanism of ribosome expression used by E. coli and show
      that this mechanism maintains the ribosomes saturated with its substrates. In
      this manner, overexpression of the highly abundant ribosomal proteins is
      prevented, and limited resources can be redirected to the synthesis of other
      growth-promoting enzymes. It turns out that the kinetic conditions for robust,
      optimal protein-partitioning, which are required for growth rate maximization
      across conditions, can be achieved with basic biochemical interactions. We show
      that inactive ribosomes are the most suitable 'signal' for tracking the
      intracellular nutritional state and for adjusting gene expression accordingly, as
      small deviations from optimal ribosome concentration cause a huge fractional
      change in ribosome inactivity. We expect to find this control logic implemented
      across fast-growing microbial species because growth rate maximization is a
      common selective pressure, ribosomes are typically highly abundant and thus
      costly, and the required control can be implemented by a small, simple network.

PMID- 25754870
TI  - Elastic properties of ascending aorta in women with previous pregnancy
      complicated by early- or late-onset pre-eclampsia.
AB  - OBJECTIVES: To evaluate the elastic properties of the ascending aorta in women
      with a previous pregnancy complicated by early-onset (EO) or late-onset (LO) pre
      eclampsia (PE) and the correlation with gestational age (GA), systolic/diastolic
      blood pressure (SBP/DBP) and mean uterine artery pulsatility index (UtA-PI) at
      diagnosis of the disease as well as with birth weight of the neonate. METHODS:
      Thirty women who had a previous pregnancy complicated by EO-PE, 30 with a
      previous pregnancy complicated by LO-PE and 30 normal controls were selected
      retrospectively from our electronic database and then recalled for assessment
      from 6 months to 4 years after delivery. Data regarding GA, SBP/DBP and mean UtA
      PI at the diagnosis of PE were obtained from medical records. At our assessment,
      aortic M-mode and tissue Doppler imaging (TDI) parameters were measured. Aortic
      diameters were assessed at end-diastole at four levels: Valsalva sinuses,
      sinotubular junction, tubular tract and aortic arch. Aortic compliance,
      distensibility, stiffness index (SI), Peterson's elastic modulus (EM), pulse-wave
      velocity and M-mode strain were calculated using standard formulae. Aortic
      expansion velocity, early and late diastolic retraction velocities and peak
      systolic tissue strain (TDI-epsilon) were determined. RESULTS: Aortic diameters
      at the four levels were significantly greater in both EO-PE and LO-PE groups than
      in controls. Aortic compliance and distensibility and TDI-epsilon were lower in
      EO-PE than in LO-PE (P  = 0.001, P  = 0.002 and P  = 0.011, respectively) and
      controls (P  = 0.037, P  = 0.044 and P  = 0.013, respectively). SI and EM were
      higher in EO-PE than in LO-PE (P  = 0.001 and P  < 0.001, respectively) and than
      in controls (P = 0.035 and P  = 0.036, respectively). Multivariate analysis
      showed GA, DBP and UtA-PI at diagnosis of PE to be independent predictors of
      aortic elastic properties. CONCLUSIONS: Elastic properties of the ascending aorta
      were altered in women with a previous pregnancy complicated by EO-PE, but not in
      those with LO-PE. Copyright (c) 2015 ISUOG. Published by John Wiley & Sons Ltd.

PMID- 25754872
TI  - NEXAFS and XPS studies of nitrosyl chloride.
AB  - The electronic structure of nitrosyl chloride (ClNO) has been investigated in the
      gas phase by X-ray Photoelectron (XPS) and Near Edge X-ray Absorption Fine
      Structure (NEXAFS) spectroscopy at the Cl 2p, Cl 2s, N 1s and O 1s edges in a
      combined experimental and theoretical study. The theoretical calculations at
      different levels of approximation predict ionization potential values in good
      agreement with the experimental data and allow us to assign the main features of
      the absorption spectra. An unexpected failure of the density functional model is,
      however, observed in the calculation of the Cl 2s binding energy, which is
      related to a large self-interaction error. Largely different photoabsorption
      cross-section patterns are experimentally observed in core excitations from the
      investigated quantum shells (n = 1, 2). This finding is confirmed by the
      oscillator strength distributions calculated at different absorption edges; in
      the case of the n = 2 shell the bands below the threshold are extremely weak and
      most of the absorption intensity is due to excitations in the continuum. 

PMID- 25754871
TI  - Willingness to access an in-hospital supervised injection facility among
      hospitalized people who use illicit drugs.
AB  - BACKGROUND: Despite the reliance on abstinence-based drug policies within
      hospital settings, illicit drug use is common among hospitalized patients with
      severe drug addiction. Hospitalized patients who use illicit drugs (PWUDs) have
      been known to resort to high-risk behavior to conceal their drug use from
      healthcare providers. Novel interventions with the potential to reduce high-risk
      behavior among PWUDs in hospital settings have not been well studied. OBJECTIVE:
      The objective of the study was to examine factors associated with willingness to
      access an in-hospital supervised injection facility (SIF). DESIGN: Data were
      derived from participants enrolled in 2 Canadian prospective cohort studies
      involving PWUDs between June 2013 and November 2013. A cross-sectional study
      surveying various sociodemographic characteristics, drug use patterns, and
      experiences was conducted. SETTING: Vancouver, Canada. MEASUREMENTS: Bivariable
      and multivariable logistic regression analyses were used to explore factors
      significantly associated with willingness to access an in-hospital SIF. RESULTS:
      Among 732 participants, 499 (68.2%) would be willing to access an in-hospital
      SIF. In multivariable analyses, factors positively and significantly associated
      with willingness to access an in-hospital SIF included: daily heroin injection
      (adjusted odds ratio [AOR] = 1.90; 95% confidence interval [CI]: 1.20-3.11);
      having used illicit drugs in hospital (AOR = 1.63; 95% CI: 1.18-2.26); and having
      recently used an SIF (AOR = 1.53; 95% CI: 1.10-2.15). CONCLUSIONS: Our findings
      highlight the potential of in-hospital SIFs to complement existing harm reduction
      programs that serve PWUD. Moreover, an in-hospital SIF may minimize the harms
      associated with high-risk illicit drug use in the hospital.

PMID- 25754873
TI  - In honor of Vladimir A. Shuvalov: light energy conversion in photosynthesis.

PMID- 25754874
TI  - A comparative study on the self-assembly of an amyloid-like peptide at water
      solid interfaces and in bulk solutions.
AB  - In the past years the self-assembly of amyloid-like peptides has attracted
      increasing attentions, because it is highly related to neurodegenerative diseases
      and has a potential for serving as nanomaterial to fabricate novel and useful
      nanostructures. In this paper, we focused on the role of interfacial conditions
      in the self-assembly of an amyloid-like peptide, termed Pep11. It was found that,
      when dissolved in bulk solutions, Pep11 formed into beta-sheet structures and
      assembled into long filaments in several hours, as revealed by Thioflavin T
      fluorescence and transmission electron microscopy (TEM) morphology
      characterization, respectively. When the peptide solution was added onto a
      mica/HOPG substrate, peptide filaments with three preferred orientations with an
      angle of 60 degrees  to each other were formed immediately, as imaged in situ by
      atomic force microscopy (AFM). However, the kinetics in filament formation and
      the morphologies of the formed beta sheet either on HOPG and mica or in bulk
      solutions were quite different. These results indicate that the interfacial
      properties dramatically affect the peptide self-assembly process.

PMID- 25754875
TI  - Treg-cell depletion promotes chemokine production and accumulation of CXCR3(+)
      conventional T cells in intestinal tumors.
AB  - Colorectal cancer (CRC) is one of the most prevalent tumor types worldwide and
      tumor-infiltrating T cells are crucial for anti-tumor immunity. We previously
      demonstrated that Treg cells from CRC patients inhibit transendothelial migration
      of conventional T cells. However, it remains unclear if local Treg cells affect
      lymphocyte migration into colonic tumors. By breeding APC(Min/+) mice with
      depletion of regulatory T cells mice, expressing the diphtheria toxin receptor
      under the control of the FoxP3 promoter, we were able to selectively deplete Treg
      cells in tumor-bearing mice, and investigate the impact of these cells on the
      infiltration of conventional T cells into intestinal tumors. Short-term Treg-cell
      depletion led to a substantial increase in the frequencies of T cells in the
      tumors, attributed by both increased infiltration and proliferation of T cells in
      the Treg-cell-depleted tumors. We also demonstrate a selective increase of the
      chemokines CXCL9 and CXCL10 in Treg-cell-depleted tumors, which were accompanied
      by accumulation of CXCR3(+) T cells, and increased IFN-gamma mRNA expression. In
      conclusion, Treg-cell depletion increases the accumulation of conventional T
      cells in intestinal tumors, and targeting Treg cells could be a possible anti
      tumor immunotherapy, which not only affects T-cell effector functions, but also
      their recruitment to tumors. 

PMID- 25754876
TI  - Cardiometabolic Effects of a New Class of Antidiabetic Agents.
AB  - PURPOSE: Within the past decade, many new classes of drugs have received approval
      from the US Food and Drug Administration for treatment of type 2 diabetes
      mellitus, including glucagon-like peptide-1agonists, dipeptidyl peptidase-4
      inhibitors, and the sodium-glucose cotransporter-2 inhibitors. Many trials have
      been performed, and several more are currently ongoing to evaluate these drugs.
      This review addresses the broad therapeutic and pleiotropic effects of these
      drugs. The review also discusses the role of these drugs in the treatment
      paradigm for type 2 diabetes and identifies patients who would be suitable
      candidates for treatment with these drugs. METHODS: In this comprehensive
      evidence-based review, the following databases were searched from 1990 to the
      present: PubMed/MEDLINE, Scopus, CINAHL, ClinicalTrials.gov, the World Health
      Organization International Clinical Trials Registry Portal, and the American
      Diabetes Association and European Association for the Study of Diabetes abstract
      databases. Randomized clinical trials (RCTs) were only included for the main
      therapeutic and cardiovascular (CV) effects of these drug classes. For
      pleiotropic effects, RCTs were included unless no RCTs exist, in which case other
      studies as specified in the detailed Methods section were included. FINDINGS: All
      3 drug classes are effective in lowering hemoglobin A1c between 0.4% and 1.4%,
      depending on the drug class and population selected. These drug classes have
      beneficial effects on CV risk factors, such as weight, lipids, and blood
      pressure, in addition to lowering blood glucose levels. The CV tolerability of
      some drugs has been evaluated and found to be neutral; however, most trials are
      currently ongoing to assess CV tolerability. There are no concrete guidelines to
      determine where these drugs fit in the diabetes management paradigm, and there
      are ongoing trials to determine the best combination drug with metformin.
      IMPLICATIONS: These 3 drug classes will potentially increase the armamentarium
      against hyperglycemia. However, the specific combinations with other antidiabetic
      drugs and populations that will best benefit from these drugs are still being
      tested. Future research is also being conducted on the use of glucagon-like
      peptide-1 receptor agonists and sodium-glucose cotransporter-2 inhibitors in
      patients with type 1 diabetes.

PMID- 25754877
TI  - Detecting infection in neonates: promises and challenges of a salivary approach.
AB  - Premature newborns present unique challenges for the caregiver. Their clinical
      fragility and immature immune system places them at increased risk for bacterial
      and viral infections. Current clinical standard of care mandates invasive
      phlebotomy to assess an infant for an infection. However, serial blood draws can
      lead to blood transfusions and the infliction of noxious stimuli to this
      vulnerable population. Salivary screening for common neonatal morbidities, such
      as infections, could vastly improve the care for these infants and positively
      affect their long-term clinical outcomes. Recent technological advancements have
      improved our ability to detect thousands of proteins and/or microbes from a
      single salivary sample, making noninvasive assessment in neonates a possibility.
      This article reviews the clinical applications and challenges associated with
      integrating salivary analysis for infectious surveillance into the neonatal
      population. 

PMID- 25754878
TI  - APOE epsilon4 genotype predicts memory for everyday activities.
AB  - The apolipoprotein E (ApOE) epsilon4 allele is associated with neuropathological
      buildup of amyloid in the brain, and with lower performance on some laboratory
      measures of memory in some populations. In two studies, we tested whether ApOE
      genotype affects memory for everyday activities. In Study 1, participants aged 20
      79 years old (n = 188) watched movies of actors engaged in daily activities and
      completed memory tests for the activities in the movies. In Study 2, cognitively
      healthy and demented older adults (n = 97) watched and remembered similar movies,
      and also underwent structural MRI scanning. All participants provided saliva
      samples for genetic analysis. In both samples we found that, in older adults,
      ApOE epsilon4 carriers demonstrated worse everyday memory performance than did
      epsilon4 noncarriers. In Study 2, ApOE epsilon4 carriers had smaller medial
      temporal lobes (MTL) volumes, and MTL volume mediated the relationship between
      ApOE genotype and everyday memory performance. These everyday memory tasks
      measure genetically determined cognitive decline that can occur prior to a
      clinical diagnosis of dementia. Further, these tasks are easily administered and
      may be a useful clinical tool in identifying epsilon4 carriers who may be at risk
      for MTL atrophy and further cognitive decline that is a common characteristic of
      the earliest stages of Alzheimer's disease.

PMID- 25754879
TI  - UV-B-induced anthocyanin accumulation in hypocotyls of radish sprouts continues
      in the dark after irradiation.
AB  - BACKGROUND: Raphanus sativus L. cv. Yanghua sprouts are rich in health-promoting
      anthocyanins; thus hypocotyls show a red color under light. In this study,
      effects of UV-B irradiation at 5 W m(-2) on anthocyanin biosynthesis in the
      hypocotyls of radish sprouts were investigated. RESULTS: Anthocyanins began to
      accumulate rapidly from 24 h irradiation and increased continuously until 48 h,
      showing a similar pattern to phenylalanine ammonia lyase (PAL) activity, with a
      correlation coefficient of 0.804. The expression of DFR and ANS paralleled the
      upward trend in anthocyanin accumulation, while CHS, CHI and F3H were upregulated
      before accumulation. When sprouts were moved into the dark from UV-B, the
      anthocyanin accumulation did not stop immediately. By contrast, anthocyanin
      accumulated continuously for more than 12 h in the dark, which was further
      supported by the significantly higher PAL activity monitored at 24 h after
      irradiation. Similarly, the transcript levels of anthocyanin biosynthesis-related
      genes were much higher over 6 h after 12 h UV-B irradiation. CONCLUSION: UV-B
      induced anthocyanin accumulation continues in the dark after irradiation, which
      was supported by unfading PAL activity and high levels of biosynthesis-related
      genes. This will provide evidence to produce high-quality sprouts with more
      anthocyanins but less energy wastage in practice.

PMID- 25754880
TI  - Survival and prognostic indicators of Budd-Chiari syndrome: a systematic review
      of 79 studies.
AB  - This paper aimed to systematically review the survival of Budd-Chiari syndrome
      and to identify the most robust prognostic predictors. Overall, 79 studies were
      included. According to the treatment modalities, the median 1-, 5- and 10-year
      survival rate was 93, 83 and 73% after interventional radiological treatment; 81,
      75 and 72.5% after surgery other than liver transplantation; 82.5, 70.2 and 66.5%
      after liver transplantation and 68.1, 44.4% and unavailable after medical therapy
      alone. According to the publication years, the median 1-, 5- and 10-year survival
      rate was 68.6, 44.4% and unavailable before 1990; 75.1, 69.5 and 57% during the
      year 1991-1995; 77, 69.6 and 65.6% during the year 1996-2000; 86.5, 74 and 63.5%
      during the year 2001-2005 and 90, 82.5 and 72% after 2006. Bilirubin, creatinine
      and ascites were more frequently identified as significant prognostic factors in
      univariate analyses. But their statistical significance was less frequently
      achieved in multivariate analyses. 

PMID- 25754881
TI  - Clinicopharmacological profile of the fixed-dose combination of aclidinium
      bromide and formoterol fumarate in the management of chronic obstructive
      pulmonary disease.
AB  - The recent Global Initiative for Chronic Obstructive Lung Disease (GOLD) chronic
      obstructive pulmonary disease (COPD) guidelines consider symptoms and
      exacerbation history in addition to the degree of airflow obstruction for
      classifying patients. The improvement of symptoms is principally provided by
      bronchodilators, using beta2 agonists and antimuscarinic agents. Aclidinium
      bromide is a novel long-acting antimuscarinic agent licensed for use in patients
      with COPD. Novel fixed-dose combinations that are either licensed or in their
      late phase of development include vilanterol/umeclidinium,
      indacaterol/glycopyrronium, olodaterol/tiotropium and formoterol/aclidinium.
      Fixed-dose combinations of aclidinium/formoterol have been evaluated in COPD
      patients and evidence suggests that this is efficacious, safe, has a quick onset
      of action and is well tolerated. This review provides a clinico-pharmacological
      profile of this compound. 

PMID- 25754882
TI  - Scleral tunnel intraocular lens explantation.

PMID- 25754883
TI  - Additive and epistatic genome-wide association for growth and ultrasound scan
      measures of carcass-related traits in Brahman cattle.
AB  - Genome-wide association studies are routinely used to identify genomic regions
      associated with traits of interest. However, this ignores an important class of
      genomic associations, that of epistatic interactions. A genome-wide interaction
      analysis between single nucleotide polymorphisms (SNPs) using highly dense
      markers can detect epistatic interactions, but is a difficult task due to
      multiple testing and computational demand. However, It is important for revealing
      complex trait heredity. This study considers analytical methods that detect
      statistical interactions between pairs of loci. We investigated a three-stage
      modelling procedure: (i) a model without the SNP to estimate the variance
      components; (ii) a model with the SNP using variance component estimates from
      (i), thus avoiding iteration; and (iii) using the significant SNPs from (ii) for
      genome-wide epistasis analysis. We fitted these three-stage models to field data
      for growth and ultrasound measures for subcutaneous fat thickness in Brahman
      cattle. The study demonstrated the usefulness of modelling epistasis in the
      analysis of complex traits as it revealed extra sources of genetic variation and
      identified potential candidate genes affecting the concentration of insulin-like
      growth factor-1 and ultrasound scan measure of fat depth traits. Information
      about epistasis can add to our understanding of the complex genetic networks that
      form the fundamental basis of biological systems. 

PMID- 25754884
TI  - Valvular disease: Prognostic relevance of pulmonary hypertension in valvular
      disease.

PMID- 25754885
TI  - Cardiovascular risk assessment: a global perspective.
AB  - An important strategy in primary prevention of cardiovascular diseases (CVD) is
      the early identification of high-risk individuals. Effective implementation of a
      strategy to identify these individuals in a clinical setting is reliant on the
      availability of appropriate CVD risk-assessment models and guideline
      recommendations. Several well-known models for CVD risk assessment have been
      developed and utilized in the USA and Europe, but might not be suitable for use
      in other regions or countries. Very few reports have discussed the development of
      risk-assessment models and recommendations from a global perspective. In this
      Review, we discuss why risk-assessment methods developed from studies in one
      geographical region or ethnic population might not be suitable for other regions
      or populations, and examine the availability and characteristics of predictive
      models in areas beyond the USA or Europe. In addition, we compare the differences
      in risk-assessment recommendations outlined in CVD clinical guidelines from
      developed and developing countries, and consider their potential effect on
      clinical practice. This overview of cardiovascular risk assessment from a global
      perspective can potentially guide low-to-middle-income countries in the
      development or validation of their own CVD risk-assessment models, and the
      formulation of recommendations in their own clinical guidelines according to
      local requirements. 

PMID- 25754887
TI  - Fluorous-assisted synthesis of (E)-5-[3-aminoallyl]-uridine-5'-O-triphosphate.
AB  - An efficient, reliable method for the chemical synthesis of (E)-5-[3-aminoallyl]
      uridine-5'-O-triphosphate (AA-UTP), starting from 5-iodouridine, is described.
      This new strategy features the involvement of one-pot triphosphate formation and
      fluorous solid-phase extraction (F-SPE). The one-pot synthesis involves the mono
      phosphorylation of fluorous-tagged uridine, followed by the reaction with
      pyrophosphate to afford the fluorous-tagged AA-UTP. The F-SPE is achieved by
      installing a fluorous-tag onto the uridine prior to triphosphate formation,
      purification via F-SPE, and cleavage of the fluorous-tag. It is worth mentioning
      that this protocol produces AA-UTP in high yield and purity using one simple F
      SPE; no conventional column chromatography is involved.

PMID- 25754886
TI  - Severe X-linked chondrodysplasia punctata in nine new female fetuses.
AB  - OBJECTIVES: Conradi-Hunermann-Happle [X-linked dominant chondrodysplasia punctata
      2 (CDPX2)] syndrome is a rare X-linked dominant skeletal dysplasia usually lethal
      in men while affected women show wide clinical heterogeneity. Different EBP
      mutations have been reported. Severe female cases have rarely been reported, with
      only six antenatal presentations. METHODS: To better characterize the phenotype
      in female fetuses, we included nine antenatally diagnosed cases of women with EBP
      mutations. All cases were de novo except for two fetuses with an affected mother
      and one case of germinal mosaicism. RESULTS: The mean age at diagnosis was 22
      weeks of gestation. The ultrasound features mainly included bone abnormalities:
      shortening (8/9 cases) and bowing of the long bones (5/9), punctuate epiphysis
      (7/9) and an irregular aspect of the spine (5/9). Postnatal X-rays and
      examination showed ichthyosis (8/9) and epiphyseal stippling (9/9), with frequent
      asymmetric short and bowed long bones. The X-inactivation pattern of the familial
      case revealed skewed X-inactivation in the mildly symptomatic mother and random X
      inactivation in the severe fetal case. Differently affected skin samples of the
      same fetus revealed different patterns of X-inactivation. CONCLUSION: Prenatal
      detection of asymmetric shortening and bowing of the long bones and cartilage
      stippling should raise the possibility of CPDX2 in female fetuses, especially
      because the majority of such cases involve de novo mutations.

PMID- 25754888
TI  - Characterization of thioether-linked protein adducts of DNA using a Raney-Ni
      mediated desulfurization method and liquid chromatography-electrospray-tandem
      mass spectrometry.
AB  - This unit contains a complete procedure for the detection and structural
      characterization of DNA protein crosslinks (DPCs). The procedure also describes
      an approach for the quantitation of the various structurally distinct DPCs.
      Although various methods have been described in the literature for labile DPCs,
      characterization of nonlabile adducts remain a challenge. Here we present a novel
      approach for characterization of both labile and non-labile adducts by the use of
      a combination of chemical, enzymatic, and mass spectrometric approaches. A Raney
      Ni-catalyzed reductive desulfurization method was used for removal of the bulky
      peptide adducts, enzymatic digestion was used to digest the protein to smaller
      peptides and DNA to nucleosides, and finally LC-ESI-tandem mass spectrometry (MS)
      was utilized for detection and characterization of nucleoside adducts.

PMID- 25754889
TI  - Synthesis of gamma-Phosphate-Labeled and Doubly Labeled Adenosine Triphosphate
      Analogs.
AB  - This unit describes the synthesis of gamma-phosphate-labeled and doubly labeled
      adenosine triphosphate (ATP) analogs and their characterization using the
      phosphodiesterase I from Crotalus adamanteus (snake venom phosphodiesterase;
      SVPD). In the key step of the synthesis, ATP or an ATP analog, bearing a linker
      containing a trifluoroacetamide group attached to the nucleoside, are modified
      with an azide-containing linker at the terminal phosphate using an alkylation
      reaction. Subsequently, different labels are introduced to the linkers by
      transformation of one functional group to an amine and coupling to an N
      hydroxysuccinimide ester. Specifically, the Staudinger reaction of the azide is
      employed as a straightforward means to obtain an amine in the presence of various
      labels. Furthermore, the fluorescence characteristics of a fluorogenic, doubly
      labeled ATP analog are investigated following enzymatic cleavage by SVPD.

PMID- 25754890
TI  - Symmetrical diamidate prodrugs of nucleotide analogues for drug delivery.
AB  - The use of pronucleotides to circumvent the well-known drawbacks of nucleotide
      analogs has played a significant role in the area of antiviral and anticancer
      drug delivery. Several motifs have been designed to mask the negative charges on
      the phosphorus moiety of either nucleoside monophosphates or nucleoside
      phosphonates, in order to increase their hydrophobicity and allow entry of the
      compound into the cell. Among them the bis-amidate analogs, having two identical
      amino acids as masking groups through a P-N bond, represent a more recent
      approach for the delivery of nucleotide analogs, endowed with antiviral or
      anticancer activity. Different synthetic strategies are commonly used for
      preparing phosphorodiamidates of nucleosides. In this protocol, we would like to
      focus on the description of the synthetic methodology that in our hand gave the
      best results using 2'-3'-didehydro-2'-3'-dideoxythymidine (d4T, Stavudine) as
      model nucleoside. A second strategy for preparing diamidates of nucleoside
      phosphonates will be reported using {[2-(6-amino-9 H-purin-9
      yl)ethoxy]methyl}phosphonic acid (PMEA, adefovir) as model substrate.

PMID- 25754891
TI  - Microwave-assisted phosphitylation of DNA and RNA nucleosides and their analogs.
AB  - Microwave-assisted chemical phosphitylation of novel nucleoside analogs
      containing a ribulose sugar unit was successful with yields ranging from 50% to
      79% using 2-cyanoethyl-N,N-diisopropyl chlorophosphoramidite as the
      phosphitylating reagent. The resultant phosphoramidite products remained intact,
      with no signs of degradation over extended reaction times (up to 60 min) at an
      elevated temperature (65 degrees C). When the same microwave-mediated
      phosphitylating protocols were applied to canonical DNA and RNA nucleoside
      monomers as substrates, using either 2-cyanoethyl-N,N,-diisopropyl
      chlorophosphoramidite or 2-cyanoethyl-N,N,N',N'-tetraisopropyl phosphane with an
      activator, 40% to 90% yields of DNA and RNA phosphoramidites were obtained within
      10 to 15 min. These results demonstrate that microwave-assisted phosphitylation
      is an efficient alternative to standard phosphitylating conditions that can be
      expanded and refined to include a variety of substrates.

PMID- 25754893
TI  - Inferior alveolar nerve function recovers after decompression of large mandibular
      cystic lesions.
AB  - OBJECTIVE: The treatment of large mandibular cystic lesions (diameter > 35 mm) is
      controversial. Few studies determine the inferior alveolar nerve function after
      decompression which is one of the major options for treating such lesions. We aim
      to investigate the recovery of inferior alveolar nerve function after
      decompression. METHODS: Twenty-two patients with large mandibular cystic lesions,
      diagnosed as keratocystic odontogenic tumor, ameloblastoma, or dentigerous cyst,
      were included. Inferior alveolar nerve function was observed by monitoring the
      pulp vitality of involved teeth (n = 64) with electric pulp test before
      decompression and 1, 3, 6, 9, 12, and 24 months after decompression,
      respectively. RESULTS: The pulp vitality of the involved teeth was significantly
      decreased before decompression. Recovery of pulp vitality could be observed after
      decompression, indicating the recovery of inferior alveolar nerve function. A
      majority (96.9%) of the vital pulp was preserved in the involved teeth after
      decompression. CONCLUSIONS: Recovery of inferior alveolar nerve function was
      remarkable in patients with large mandibular cystic lesions after decompression,
      indicated by the recovery of pulp vitality of involved teeth. When decompression
      is preferred, conservative therapy rather than root canal therapy is recommended
      for the teeth with root tip exposed in the cystic lesions and without pulposis.

PMID- 25754892
TI  - The nucleolar protein nucleophosmin is essential for autophagy induced by
      inhibiting Pol I transcription.
AB  - Various cellular stresses activate autophagy, which is involved in lysosomal
      degradation of cytoplasmic materials for maintaining nutrient homeostasis and
      eliminating harmful components. Here, we show that RNA polymerase I (Pol I)
      transcription inhibition induces nucleolar disruption and autophagy. Treatment
      with autophagy inhibitors or siRNA specific for autophagy-related (ATG) proteins
      inhibited autophagy but not nucleolar disruption induced by Pol I transcription
      inhibition, which suggested that nucleolar disruption was upstream of autophagy.
      Furthermore, treatment with siRNA specific for nucleolar protein nucleophosmin
      (NPM) inhibited this type of autophagy. This showed that NPM was involved in
      autophagy when the nucleolus was disrupted by Pol I inhibition. In contrast, NPM
      was not required for canonical autophagy induced by nutrient starvation, as it
      was not accompanied by nucleolar disruption. Thus, our results revealed that, in
      addition to canonical autophagy, there may be NPM-dependent autophagy associated
      with nucleolar disruption. 

PMID- 25754894
TI  - Meta-analysis of noncontingent reinforcement effects on problem behavior.
AB  - A meta-analysis of noncontingent reinforcement (NCR) outcomes was conducted using
      hierarchical linear modeling (a) to document the effect size for decreasing
      problem behavior, (b) to compare effect sizes for NCR using functional
      reinforcers and nonfunctional reinforcers, and (c) to document the influence of
      schedule thinning on effect size. Analyses were conducted with data from 55
      studies and 91 participants. Results indicate that NCR was associated with a very
      strong effect size (d =-1.58) for reduction of problem behavior, functional
      reinforcers were slightly more effective than nonfunctional reinforcers, and
      schedule thinning resulted in minor degradation of effect size. Meta-analysis of
      single-case design data provides a method to quantitatively estimate effect sizes
      of interventions across participants. Therefore, it allows one to identify
      important variables that are not otherwise evident in single-case data, helps to
      disseminate findings to the broader scientific community, and contributes to the
      documentation of empirically supported interventions.

PMID- 25754895
TI  - Representativeness of direct observations selected using a work-sampling
      equation.
AB  - Deciding on appropriate sampling to obtain representative samples of behavior is
      important but not straightforward, because the relative duration of the target
      behavior may affect its observation in a given sampling interval. Work-sampling
      methods, which offer a way to adjust the frequency of sampling according to a
      priori or ongoing estimates of the behavior to achieve a preselected level of
      representativeness, may provide a solution. Full-week observations of 7 behaviors
      were conducted for 3 students with autism spectrum disorder and intellectual
      disabilities. Work-sampling methods were used to select momentary time samples
      from the full time-of-interest, which produced representative samples. However,
      work sampling required impractically high numbers of time samples to obtain
      representative samples. More practical momentary time samples produced less
      representative samples, particularly for low-duration behaviors. The utility and
      limits of work-sampling methods for applied behavior analysis are discussed. 

PMID- 25754896
TI  - Increasing the efficiency of paired-stimulus preference assessments by
      identifying categories of preference.
AB  - A paired-stimulus preference assessment was conducted for 6 individuals with
      developmental disabilities. We selected stimuli that were representatives of 4
      categories: chocolate, salty and crunchy, gummy, and fruit and vegetable. For all
      6 participants, at least 3 of the 5 most preferred items came from the same
      category. On subsequent reinforcer assessments, items from the highest ranked
      preference category, some of which were included in the preference assessments
      and some of which were not, functioned as reinforcers. These findings suggest
      that after categories of preferred items are identified, clinicians may be able
      to identify reinforcers for some individuals without conducting additional
      assessments.

PMID- 25754897
TI  - Short interpregnancy interval and low birth weight: A role of parity.
AB  - OBJECTIVES: Short interpregnancy intervals (IPI) and high parity may be
      synergistically associated with the risk of unfavorable pregnancy outcomes. This
      study tests if the effect of short IPI on the odds ratio for low birth weight
      (LBW, <2,500 g) differs across parity status. METHODS: The study was carried out
      on the birth registry sample of almost 40,000 singleton, live-born infants who
      were delivered between the years 1995 and 2009 to multiparous mothers whose
      residence at the time of infant's birth was the city of Krakow. Multiple logistic
      regression analyses were used for testing the effect of IPI on the odds ratio
      (OR) for LBW, after controlling for employment, educational and marital status,
      parity, sex of the child, maternal and gestational age. Stratified analyses
      (according to parity) and tests for interaction were performed. RESULTS: Very
      short IPI (0-5 months) was associated with an increased OR for LBW, but only
      among high parity mothers with three or more births (OR = 2.64; 95% CI 1.45
      4.80). The test for interaction between very short IPI and parity on the OR for
      LBW was statistically significant after adjustment for multiple comparisons (P =
      0.04). Among low parity mothers (two births) no statistically significant
      associations were found between IPI and LBW after standardization. CONCLUSION:
      Parity may modify the association between short birth spacing and LBW. Women with
      very short IPI and high parity may have a higher risk of having LBW infants than
      those with very short IPI but low parity.

PMID- 25754898
TI  - Cost-constrained optimal sampling for system identification in pharmacokinetics
      applications with population priors and nuisance parameters.
AB  - Pharmacokinetics (PK) applications can be seen as a special case of nonlinear,
      causal systems with memory. There are cases in which prior knowledge exists about
      the distribution of the system parameters in a population. However, for a
      specific patient in a clinical setting, we need to determine her system
      parameters so that the therapy can be personalized. This system identification is
      performed many times by measuring drug concentrations in plasma. The objective of
      this work is to provide an irregular sampling strategy that minimizes the
      uncertainty about the system parameters with a fixed amount of samples (cost
      constrained). We use Monte Carlo simulations to estimate the average Fisher's
      information matrix associated to the PK problem, and then estimate the sampling
      points that minimize the maximum uncertainty associated to system parameters (a
      minimax criterion). The minimization is performed employing a genetic algorithm.
      We show that such a sampling scheme can be designed in a way that is adapted to a
      particular patient and that it can accommodate any dosing regimen as well as it
      allows flexible therapeutic strategies.

PMID- 25754899
TI  - Exogenous reinfection of tuberculosis in a low-burden area.
AB  - PURPOSE: Recurrence of tuberculosis (TB) can be the consequence of relapse or
      exogenous reinfection. The study aimed to assess the factors associated with
      exogenous TB reinfection. METHODS: Prospective cohort study based on the TB
      database, maintained at the Division of Infectious Diseases, Luigi Sacco Hospital
      (Milan, Italy). Time period: 1995-2010. INCLUSION CRITERIA: (1) >=2 episodes of
      culture-confirmed TB; (2) cure of the first episode of TB; (3) availability of
      one Mycobacterium tuberculosis isolate for each episode. Genotyping of the M.
      tuberculosis strains to differentiate relapse and exogenous reinfection. Logistic
      regression analysis was used to assess the influence of risk factors on exogenous
      reinfections. RESULT: Of the 4682 patients with TB, 83 were included. Of these,
      exogenous reinfection was diagnosed in 19 (23 %). It was independently associated
      with absence of multidrug resistance at the first episode [0, 10 (0.01-0.95), p =
      0.045] and with prolonged interval between the first TB episode and its
      recurrence [7.38 (1.92-28.32) p = 0.004]. However, TB relapses occurred until 4
      years after the first episode. The risk associated with being foreign born,
      extrapulmonary site of TB, and HIV infection was not statistically significant.
      In the relapse and re-infection cohort, one-third of the patients showed a
      worsened drug resistance profile during the recurrent TB episode. CONCLUSIONS:
      Exogenous TB reinfections have been documented in low endemic areas, such as
      Italy. A causal association with HIV infection could not be confirmed. Relapses
      and exogenous reinfections shared an augmented risk of multidrug resistance
      development, frequently requiring the use of second-line anti-TB regimens.

PMID- 25754901
TI  - The changing practice of the obstetrician.

PMID- 25754900
TI  - Reveromycin A-Induced Apoptosis in Osteoclasts Is Not Accompanied by Necrosis.
AB  - Reveromycin A (RM-A), a small natural product isolated from Streptomyces
      bacteria, is a potential osteoporosis therapeutic in that it specifically induces
      apoptosis in osteoclasts but not osteoblasts. The purpose of the study presented
      here was to further elucidate the intracellular mechanisms of RM-A death effects
      in mature osteoclasts. A specific clone of RAW264.7 murine macrophages that was
      previously characterized for its ability to acquire an osteoclast nature on
      differentiation was differentiated in the presence of receptor activator of
      nuclear factor kappa B ligand (RANKL). Subsequent staining was performed for
      tartrate-resistant acid phosphatase to confirm their osteoclast character. These
      osteoclasts were treated with ten micromolar RM-A for 2, 4, 6, 24, and 48 h at a
      pH of 5.5. Peak apoptosis induction occurred at 4-6 h as measured by caspase 3
      activity. Lactate dehydrogenase release assay revealed no significant RM-A
      induced necrosis. Western blot analysis of cytoplasmic extracts demonstrated
      activation of caspase 9 (2.3-fold at 2 h and 2.6-fold at 4 h, each P < 0.05) and
      no significant changes in Bcl-XL . In nuclear extracts, NFkappaB levels
      significantly increased on differentiation with RANKL but then remained constant
      through RM-A treatment. Over the extended time course studied, RM-A-induced
      apoptosis in osteoclasts was not accompanied by necrosis, suggesting that RM-A
      would likely have limited effects on immediate, neighboring bone cell types. This
      specific cell death profile is promising for potential clinical investigations of
      RM-A as a bone antiresorptive.

PMID- 25754902
TI  - Magnetic nanohybrids loaded with bimetal core-shell-shell nanorods for bacteria
      capture, separation, and near-infrared photothermal treatment.
AB  - A novel antimicrobial nanohybrid based on near-infrared (NIR) photothermal
      conversion is designed for bacteria capture, separation, and sterilization
      (killing). Positively charged magnetic reduced graphene oxide with modification
      by polyethylenimine (rGO-Fe3 O4 -PEI) is prepared and then loaded with core-shell
      shell Au-Ag-Au nanorods to construct the nanohybrid rGO-Fe3 O4 -Au-Ag-Au. NIR
      laser irradiation melts the outer Au shell and exposes the inner Ag shell, which
      facilitates controlled release of the silver shell. The nanohybrids combine
      physical photothermal sterilization as a result of the outer Au shell with the
      antibacterial effect of the inner Ag shell. In addition, the nanohybrid exhibits
      high heat conductivity because of the rGO and rapid magnetic-separation
      capability that is attributable to Fe3 O4 . The nanohybrid provides a significant
      improvement of bactericidal efficiency with respect to bare Au-Ag-Au nanorods and
      facilitates the isolation of bacteria from sample matrixes. A concentration of 25
      MUg mL(-1) of nanohybrid causes 100 % capture and separation of Escherichia coli
      O157:H7 (1*10(8) cfu mL(-1) ) from an aqueous medium in 10 min. In addition, it
      causes a 22  degrees C temperature rise for the surrounding solution under NIR
      irradiation (785 nm, 50 mW cm(-2) ) for 10 min. With magnetic separation, 30 MUg
      mL(-1) of nanohybrid results in a 100 % killing rate for E. coli O157:H7 cells.
      The facile bacteria separation and photothermal sterilization is potentially
      feasible for environmental and/or clinical treatment.

PMID- 25754903
TI  - Deriving Effective Sweep Width for Air-scent Dog Teams.
AB  - OBJECTIVE: We sought to obtain the first effective sweep widths (ESWs) ever
      measured for an air-scent search dog unit to compare their performance to
      historical data from human searchers and to initially test the validity of
      atmospheric convection as a limiting factor in air-scent search. METHODS: We used
      GPS tracks and waypoints to measure lateral hit and miss distances for the dog
      teams during blinded, randomized training tasks during a 6-year period,
      calculating ESW using the crossover method. During the tasks we collected weather
      data for determining convection. We used nonparametric statistics and least
      square regression to compare the dog ESW data with historical human data and
      weather conditions. RESULTS: The mean value of ESW for the 4 teams under all
      conditions was 95 m (95% CI, 44 to 145). The dog teams' performance was
      statistically superior to human visual searchers in detecting search subjects in
      low-visibility colors, but not subjects in high-visibility colors. A
      nonparametric correlation test of ESW vs convection gave P<.05, suggesting that
      convection may be an operationally significant factor in air-scent dog
      performance. CONCLUSIONS: The ESW methodology is applicable to air-scent dog
      teams, potentially allowing search managers to make decisions in applying
      resources operationally, as well as improving accuracy of planning calculations.
      In addition, the methods described appear to be capable, given more widely
      representative data, of making valid statistical comparisons between different
      search modalities and weather and other factors.

PMID- 25754904
TI  - Finger and Toe Temperature Responses to Cold After Freezing Cold Injury in Elite
      Alpinists.
AB  - OBJECTIVE: To assess whether previous freezing cold injuries (FCI) would affect
      digit skin temperatures and rewarming rates during a follow-up cold stress test
      protocol. DESIGN: Nonrandomized control trial. METHODS: Twenty elite alpinists
      participated; alpinists with previous FCI requiring digit amputations (injured,
      INJ: n = 10 total, n = 8 male) were compared with ability-matched, uninjured
      alpinists (control, CON: n = 10, all male). Digit skin temperature was measured
      using infrared thermography as an index of peripheral digit perfusion after a
      cold stress test, which consisted of 30 minutes of immersion in 8 degrees C
      water. RESULTS: The INJ alpinists' injured toes were warmer (approximately 6%)
      than their uninjured toes immediately after cold immersion (95% CI, 0.01 degrees
      C to 1.00 degrees C; P = .05); there were no differences between the rates of
      rewarming of injured and uninjured toes (INJ, 0.5 degrees  +/- 0.1 degrees C/min;
      CON, 0.7 degrees  +/- 0.3 degrees C/min; P = .16). Although the INJ alpinists had
      colder injured fingers immediately after the 35 degrees C warm bath compared with
      their own uninjured fingers (32.2 degrees  +/- 2.0 degrees C vs 34.5 degrees  +/-
      0.5 degrees C; P = .02), there were no differences observed between the rates of
      rewarming of injured and uninjured fingers after cold exposure (INJ, 1.1 degrees 
      +/- 0.2 degrees C/min; CON, 1.3 degrees  +/- 0.5 degrees C/min; P = .22).
      CONCLUSIONS: Even after FCI that requires digit amputation, there is no evidence
      of different tissue rates of rewarming between the injured and uninjured fingers
      or toes of elite alpinists.

PMID- 25754905
TI  - Simple scheme for encoding and decoding a qubit in unknown state for various
      topological codes.
AB  - We present a scheme for encoding and decoding an unknown state for CSS codes,
      based on syndrome measurements. We illustrate our method by means of Kitaev toric
      code, defected-lattice code, topological subsystem code and 3D Haah code. The
      protocol is local whenever in a given code the crossings between the logical
      operators consist of next neighbour pairs, which holds for the above codes. For
      subsystem code we also present scheme in a noisy case, where we allow for bit and
      phase-flip errors on qubits as well as state preparation and syndrome measurement
      errors. Similar scheme can be built for two other codes. We show that the
      fidelity of the protected qubit in the noisy scenario in a large code size limit
      is of , where p is a probability of error on a single qubit per time step.
      Regarding Haah code we provide noiseless scheme, leaving the noisy case as an
      open problem. 

PMID- 25754906
TI  - Sequential management of post-myocardial infarction ventricular septal defects.
AB  - BACKGROUND: Ventricular septal defect (VSD) after acute myocardial infarction is
      a catastrophic event. AIMS: We describe our multicentre experience of a defect
      closure strategy that combined surgery and transcatheter closure. METHODS: Data
      were obtained by retrospective chart review. RESULTS: Twenty patients (mean age,
      67 years) from three centres were studied. Median time from myocardial infarction
      to VSD was 6 (range, 3-9) days. Acute cardiogenic shock occurred in 12 (60%)
      patients. Median defect diameter by echocardiography was 18 (range, 12-28) mm.
      Median time to first surgical or percutaneous closure was 18 (range, 4-96) days.
      Twenty-seven procedures were performed in the 20 patients. Surgical closure was
      undertaken in 14 patients and contraindicated in eight, six of whom underwent
      percutaneous closure; the other two, after reconsideration, proceeded to surgical
      closure. No procedural complications occurred with percutaneous closure.
      Percutaneous closure patients were older than surgical patients (75 vs. 64 years;
      P=0.01) and had a higher mean logistic EuroSCORE (87% vs. 67%; P=0.02). Rates of
      residual shunt and mortality did not differ between surgical and percutaneous
      patients (P=0.12 and 0.3, respectively). Those who underwent early VSD closure
      (<21 days after myocardial infarction) had higher rates of residual shunt
      (P=0.09) and mortality (P=0.01), irrespective of closure strategy. The mortality
      rate was also higher after early percutaneous closure (P=0.001), but not after
      early surgery. Finally, predicted mortality (logistic EuroSCORE) was higher than
      hospital mortality (<=30 days) in our patient population (75% vs. 30%; P=0.01).
      CONCLUSION: Vigorous pursuit of closure of post-myocardial infarction VSD with a
      sequential surgical and/or percutaneous approach is recommended for improved
      outcomes.

PMID- 25754907
TI  - Collagen plug-based vascular closure devices do not decrease vascular and
      bleeding complications occurring after balloon aortic valvuloplasty.
AB  - BACKGROUND: The benefits of vascular closure devices (VCDs) in the prevention of
      vascular complications after femoral intervention remain controversial. AIM: To
      evaluate the efficiency of collagen plug-based VCDs in the prevention of femoral
      access complications after balloon aortic valvuloplasty. METHODS: We conducted a
      prospective analysis of consecutive patients who underwent balloon aortic
      valvuloplasty by femoral retrograde technique in our centre between 2009 and
      2012. Group 1 included 75 patients in whom femoral puncture haemostasis was
      obtained with the use of an 8F collagen plug-based VCD (Angio-SealTM; Saint-Jude
      Medical, Inc.); group 2 included 105 patients who had manual or mechanical groin
      compression (FemoStopTM; RADI Medical Systems, Inc.). We did not use heparin
      during the procedure. We collected data on major in-hospital adverse events,
      major bleeding (Bleeding Academic Research Consortium classification>=3) and
      vascular access complications. RESULTS: We included 180 patients with severe and
      symptomatic aortic stenosis. Indications for valvuloplasty were mainly bridge to
      transcatheter aortic valve implantation or palliative therapy (72%). The groups
      were similar in terms of median age, lower limb artery disease and body mass
      index. Vascular and bleeding complications occurred in 11.1% of patients and were
      not decreased with the use of VCDs (relative risk 2.60, 95% confidence interval
      1.10-3.09; P=0.05). These findings were consistent across all prespecified
      subgroups. Duration of hospital stay was not reduced by VCDs. CONCLUSIONS: Based
      on the results of this study, performed with small-size sheaths and without
      heparin, collagen plug-based VCDs increase femoral access complications following
      aortic valvuloplasty. Systematic use of VCDs in elderly patients, with probable
      advanced limb atherosclerosis, is questionable.

PMID- 25754908
TI  - Clinical and echographic characteristics of patients exposed to fenfluramin or
      its derivatives: Results of a prospective, single-centre, observational study.
AB  - BACKGROUND: Fenfluramine and its derivatives have been associated with
      significant risk of developing valvular heart disease but its exact prevalence
      and severity are still debated. AIM: To evaluate the clinical and
      echocardiographic characteristics of patients hospitalized in a cardiology centre
      and who had past exposure to these drugs. METHODS: Between July 2011 and February
      2012, patients admitted to the hospitalization and intensive care units at the
      University Centre of Montpellier, France were questioned about past exposure to
      fenfluramine or its derivatives. In patients who reported exposure, a
      questionnaire assessing prescribing patterns and medical history was proposed and
      echocardiography performed. All of the usual echocardiographic variables were
      analysed. We applied criteria from a French multicentre registry for diagnosis of
      drug-induced valvulopathy: leaflets and subvalvular apparatus thickening and
      retraction, leaflets loss of coaptation, no calcification, and no stenosis.
      RESULTS: Ninety-five patients exposed to these drugs were included. The majority
      were female (n=62, 65.3%), 53.2% (n=50) had diabetes and 90.5% (n=86) were
      exposed to benfluorex. Mean treatment duration was 52.3months (95% confidence
      interval [CI] 39.0-65.6). Valvular regurgitations were observed in 64.0% of
      patients (n=57) while 19.8% (n=17) had pulmonary hypertension. Highly probable
      fenfluramine-induced regurgitations were present in 18.6% (n=16) of patients,
      possibly fenfluramine-induced regurgitations in 38.2% (n=34) of patients, and
      unlikely fenfluramine-induced regurgitations in 25.8% (n=23) of patients. Highly
      probable fenfluramine-induced regurgitations were mild to moderate in severity in
      all except three patients. CONCLUSION: Considering the frequency of probable or
      possible fenfluramine-induced regurgitations and in the absence of definite
      knowledge about the evolution of drug-induced valvular disease, systematic
      questioning about fenfluramine use may be advisable in hospitalized cardiac
      patients.

PMID- 25754909
TI  - Rupture of mitral valve chordae in hypertrophic cardiomyopathy.
AB  - BACKGROUND: While occasional reports of mitral valve chordal rupture have been
      described in hypertrophic cardiomyopathy, the exact prevalence and
      characteristics of this event in a large medical cohort have not been reported.
      AIM: To assess the prevalence of mitral valve chordal rupture in hypertrophic
      cardiomyopathy and the clinical, echocardiographic, surgical and histological
      profiles of those patients. METHODS: We searched for patients with mitral valve
      chordal rupture diagnosed by echocardiography among all electronic files of
      patients admitted to our centre for hypertrophic cardiomyopathy between 2000 and
      2010. RESULTS: Among 580 patients admitted for hypertrophic cardiomyopathy, six
      patients (1%, 5 men, age 68-71 years) presented with mitral valve chordal
      rupture, symptomatic in five cases, always involving the posterior mitral
      leaflet. In all cases, echocardiography before rupture showed mitral valve
      systolic anterior motion, with anterior (and not posterior) leaflet elongation
      compared with a random sample of patients with non-obstructive hypertrophic
      cardiomyopathy (P=0.006) (and similar to that observed in obstructive
      hypertrophic cardiomyopathy). Significant resting left ventricular outflow tract
      obstruction was always present before rupture and disappeared after rupture in
      the five cases requiring mitral valve surgery for severe mitral regurgitation.
      Histological findings were consistent with extensive myxomatous degeneration in
      all cases. CONCLUSION: Mitral valve chordal rupture is: infrequent in
      hypertrophic cardiomyopathy; occurs in aged patients with obstructive disease;
      involves, essentially, the posterior mitral leaflet; and causes, in general,
      severe mitral regurgitation requiring surgery. Myxomatous degeneration may be the
      substrate for rupture in these patients.

PMID- 25754910
TI  - From epoxidized linseed oil to bioresin: an overall approach of epoxy/anhydride
      cross-linking.
AB  - Biorenewable resources can be used as green monomers to design tailored
      structures for formulations that can play an important role as functional
      materials. The choice of optimal structures depends on the targeted properties
      and applications. This work focuses on the elaboration of biobased materials with
      toughened mechanical properties based on epoxidized linseed oil. This result was
      obtained by an overall approach of cross-linking process, that is, starting with
      the optimal choice of hardeners and finally favoring the side reactions of
      polymerization. Therefore, the anionic alternating copolymerization of epoxide
      with mono- and dianhydrides was investigated to tailor the parameters that led to
      maximal conversions and properties. The obtained highly cross-linked networks
      perform well, as demonstrated by good impact strengths, high glass transition
      temperatures, and excellent thermal stability, which opens up the possibility of
      using these emergent materials for industrial applications. 

PMID- 25754911
TI  - Controllable magnetic correlation between two impurities by spin-orbit coupling
      in graphene.
AB  - Two magnetic impurities on the edge of a zigzag graphene nanoribbon strongly
      interact with each other via indirect coupling, which can be mediated by
      conducting carriers. By means of Quantum Monte Carlo (QMC) simulations, we find
      that the spin-orbit coupling lambda and the chemical potential MU in system can
      be used to drive the transition of local-spin exchange from ferromagnetism to
      anti-ferromagnetism. Since the tunable ranges for lambda and MU in graphene are
      experimentally reachable, we thus open the possibilities for its device
      application. The symmetry in spatial distribution is broken by the vertical and
      the transversal spin-spin correlations due to the effect of spin-orbit coupling,
      leading to the spatial anisotropy of spin exchange, which distinguish our
      findings from the case in normal Fermi liquid. 

PMID- 25754912
TI  - Childhood obesity affects adult metabolic syndrome and diabetes.
AB  - We seek to observe the association between childhood obesity by different
      measures and adult obesity, metabolic syndrome (MetS), and diabetes. Thousand two
      hundred and nine subjects from "Beijing Blood Pressure Cohort Study" were
      followed 22.9 +/- 0.5 years in average from childhood to adulthood. We defined
      childhood obesity using body mass index (BMI) or left subscapular skinfold
      (LSSF), and adult obesity as BMI >= 28 kg/m(2). MetS was defined according to the
      joint statement of International Diabetes Federation and American Heart
      Association with modified waist circumference (>= 90/85 cm for men/women).
      Diabetes was defined as fasting plasma glucose >= 7.0 mmol/L or blood glucose 2 h
      after oral glucose tolerance test >= 11.1 mmol/L or currently using blood glucose
      lowering agents. Multiple linear and logistic regression models were used to
      assess the association. The incidence of adult obesity was 13.4, 60.0, 48.3, and
      65.1 % for children without obesity, having obesity by BMI only, by LSSF only,
      and by both, respectively. Compared to children without obesity, children obese
      by LSSF only or by both had higher risk of diabetes. After controlling for adult
      obesity, childhood obesity predicted independently long-term risks of diabetes
      (odds ratio 2.8, 95 % confidence interval 1.2-6.3) or abdominal obesity (2.7, 1.6
      4.7) other than MetS as a whole (1.2, 0.6-2.4). Childhood obesity predicts long
      term risk of adult diabetes, and the effect is independent of adult obesity. LSSF
      is better than BMI in predicting adult diabetes.

PMID- 25754913
TI  - Immunoregulatory molecules in patients with gestational diabetes mellitus.
AB  - Induction of maternal-fetal immune tolerance is essential for the development of
      normal pregnancy. Impaired expression of costimulatory molecules may lead to
      intense inflammatory reaction, a mechanism involved in the pathophysiology of
      gestational diabetes mellitus (GDM). The aim of this study was to investigate
      whether immunoregulatory molecules are involved in the physiopathology of GDM.
      This case-control study included 30 healthy pregnant women and 20 GDM patients.
      Flow cytometry was used to assess peripheral blood T subpopulations (CD4(+) and
      CD8(+)), the expression of immunoregulatory molecules (CD28, ICOS, CTLA-4, and PD
      1) and activation markers (CD69 and HLA-DR). Compared to healthy women, GDM
      patients had a significantly higher frequency of CD4(+)CD69(+) and CD8(+)CD69(+)
      T cells; only patients with insulin-treated GDM had increased numbers of
      CD4(+)HLA-DR(+) T cells. We also observed significantly higher percentages of
      CD4(+)CD28(+)HLA-DR(+), CD3(+)CD4(+)ICOS(+), CD3(+)CD4(+)PD-1(+),
      CD8(+)CD28(+)CD69(+), CD8(+)CD28(+)HLA-DR(+), CD8(+)CTLA-4(+)HLA-DR(+), and
      CD3(+)CD8(+)ICOS(+) T cells and lower frequency of CD3(+)CD4(+)CTLA-4(+),
      CD3(+)CD8(+)CTLA-4(+), and CD8(+)ICOS(+)HLA-DR(+) T cells in GDM patients
      compared to healthy pregnant women. This first study assessing costimulatory
      molecules in GDM patients shows that these patients have exacerbated markers of T
      cell activation along with CTLA-4 deficiency, findings that indicate that the
      maternal-fetal tolerance is compromised in these patients.

PMID- 25754914
TI  - Complete disappearance of liver metastases in a patient with iodine-refractory
      differentiated thyroid cancer subjected to sorafenib re-challenge.

PMID- 25754915
TI  - Growth hormone deficiency in patients with obesity.

PMID- 25754916
TI  - Severe gastrointestinal autonomic dysfunction in a diabetic boy.

PMID- 25754917
TI  - CNKSR2 deletions: a novel cause of X-linked intellectual disability and seizures.

PMID- 25754918
TI  - Identification and characterization of the diuretic hormone 31 receptor in the
      silkworm Bombyx mori.
AB  - The receptor for diuretic hormone 31 (DH31R) was identified in the silkworm
      Bombyx mori. A heterologous expression system revealed that an orphan G-protein
      coupled receptor, BNGR-B1, responded to DH31 and upregulated the intracellular
      cAMP level. DH31R (BNGR-B1) was predominantly expressed in the anterior silk
      gland, midgut, and ovary, whereas DH31 was predominantly expressed in the central
      nervous system and midgut. 

PMID- 25754919
TI  - Electrochemical immunosensor for botulinum neurotoxin type-E using covalently
      ordered graphene nanosheets modified electrodes and gold nanoparticles-enzyme
      conjugate.
AB  - In this work, a novel electrochemical immunosensor was developed for the
      detection of botulinum neurotoxin-E (BoNT/E). This method relied on graphene
      nanosheets-aryldiazonium salt modified glassy carbon electrodes (GCE) as sensing
      platform and enzyme induced silver nanoparticles (AgNPs) deposited on gold
      nanoparticles (AuNPs) as signal amplifier. Herein, a GCE was electrografted with
      mixed monolayer of phenyl and aminophenyl (Ph-PhNH2/GCE) by diazotization
      reaction. Further, graphene nanosheets (GNS) were covalently attached on
      electrode surface (GNS/Ph-PhNH2/GCE). Field emission scanning electron microscopy
      (FE-SEM), X-ray diffraction (XRD), atomic force microscopy (AFM), electrochemical
      impedance spectroscopy (EIS) and cyclic voltammetry (CV) were employed to
      characterize synthesized graphene oxide and modified electrode surfaces. In the
      sandwich immunoassay format, the sensitivity was amplified using rabbit anti
      mouse IgG-alkaline phosphatase (RalphaMIgG-ALP) functionalized with gold
      nanoparticles (RalphaMIgG-ALP/AuNPs). In order to study the immunosensing
      performance of GNS/Ph-PhNH2/GCE, first the capturing antibody (rabbit-anti BoNT/E
      antibody) was covalently immobilized via EDC/NHS chemistry. Further, the
      electrode was sequentially subjected to sample containing spiked BoNT/E,
      revealing antibody (mouse-anti BoNT/E) followed by RalphaMIgG-ALP/AuNPs. 3
      indoxyl phosphate (3-IP) was used as substrate which finally reduces the silver
      ions. The deposited AgNPs on electrode surface were determined by linear sweep
      voltammetry (LSV). The developed electrochemical immunosensor could detect BoNT/E
      with linear range from 10pg/ml to 10ng/ml with the minimum detection limit of
      5.0pg/ml and total analysis time of 65min. In addition, the immunosensor was
      successfully evaluated against food samples (orange juice and milk). 

PMID- 25754920
TI  - In-source fragmentation and correlation analysis as tools for metabolite
      identification exemplified with CE-TOF untargeted metabolomics.
AB  - The role of non-targeted metabolomics with its discovery power is constantly
      growing in many different fields of science. However, its biggest advantage of
      uncovering the unexpected is turning into one of its biggest bottlenecks,
      particularly in metabolite identification. Among different methods for metabolite
      identification or ID confirmation, tandem MS analysis plays a very important
      role. However, this method is limited to only certain types of MS analysers,
      making for example TOF-MS inaccessible for this type of metabolite
      identification. To overcome this, in-source fragmentation has been used to
      fragment molecules and obtain product ions. Since the molecule of interest is not
      isolated prior to its fragmentation, the acquired spectrum contains many
      different signals arising from the fragmentation of all compounds present in the
      sample. Therefore, to assign product ions to their precursors, a novel use of
      correlation analysis was tested with r >=0.9 as an assignation of a product ion
      belonging to the precursor. This method and chosen cut-off was tested on three
      different sample complexity levels: conducting the analysis on a single standard,
      mix of co-eluting standards and on a plasma sample. Obtained results clearly
      proved the effectiveness of the proposed methodology for metabolite ID
      confirmation. Moreover, the proposed strategy can be successfully applied for
      semi-quantification of co-eluting molecules with the same monoisotopic mass but
      that differ in fragmentation pattern. The proposed methodology can greatly
      improve the robustness and throughput of identification in metabolomics studies
      by use of TOF-MS, which is crucial to obtain meaningful and trustful results.

PMID- 25754921
TI  - Hyperammonemic syndrome after Roux-en-Y gastric bypass.
AB  - OBJECTIVE: Hyperammonemic encephalopathy is an uncommon but severe complication
      of the Roux-en-Y gastric bypass surgery for obesity. Mechanisms underlying this
      complication are incompletely understood, resulting in delayed recognition and
      management. This study evaluated common laboratory findings and possible etiology
      of hyperammonemic encephalopathy after successful Roux-en-Y gastric bypass
      surgery. METHODS: A retrospective review of 20 patients identified through our
      own clinical practice was conducted, with the addition of similar cases from
      other institutions identified through the review of literature. RESULTS: Patients
      presenting with hyperammonemic encephalopathy after Roux-en-Y gastric bypass
      surgery presented with overlapping clinical and laboratory findings. Common
      features included: (1) weight loss following successful Roux-en-Y gastric bypass
      for obesity; (2) hyperammonemic encephalopathy accompanied by elevated plasma
      glutamine levels; (3) absence of cirrhosis; (4) hypoalbuminemia; and (5) low
      plasma zinc levels. The mortality rate was 50%. Ninety-five percent of patients
      were women. Three patients were diagnosed with proximal urea cycle disorders. One
      patient experienced improvement in the hyperammonemia after surgical correction
      of spontaneous splenorenal shunt. CONCLUSIONS: Hyperammonemic encephalopathy
      after Roux-en-Y gastric bypass surgery is a newly recognized, potentially fatal
      syndrome with diverse pathophysiologic mechanisms encompassing genetic and
      nongenetic causes.

PMID- 25754922
TI  - Comments on 'a critical look at prospective surveillance using a scan statistic'
      by T. Correa, M. Costa, and R. Assuncao.

PMID- 25754923
TI  - Response to commentary on 'a critical look at prospective surveillance using a
      scan statistic'.

PMID- 25754925
TI  - Cloning, sequence analysis and expression profiles of Toll-like receptor 7 from
      Chinese giant salamander Andrias davidianus.
AB  - The Chinese giant salamander, Andrias davidianus, is the largest extant amphibian
      species in the world, which is of significance due to its specific position in
      the evolutionary history of vertebrates. Currently, limited information about the
      innate immune system of this animal is known. In this study, the toll-like
      receptor 7 (TLR7), designated CgsTLR7, was cloned from Chinese giant salamander,
      A. davidianus. The full-length cDNA of CgsTLR7 is 3747 bp, with an open reading
      frame of 3150 bp, encoding 1049 amino acids. The TLR family motifs, including the
      leucine-rich repeat (LRR) and Toll/interleukin (IL)-1 receptor (TIR) domain are
      conserved in CgsTLR7, which includes 19 LRRs and a TIR domain. The predicted
      amino acid sequence of CgsTLR7 has 71%, 65%, 63% and 55% identity with turtle,
      chicken, human and fugu TLR7 homologues, respectively. Phylogenetic analysis
      showed that CgsTLR7 is closest to that of frog TLR7 among the examined species.
      Quantitative real-time PCR analysis revealed broad expression of CgsTLR7 in
      tissues from apparently healthy Chinese giant salamanders with the highest
      expression in the liver and the lowest expression in the intestine. The mRNA
      expression was up-regulated and reached a peak level in the kidney, liver and
      spleen at 12 h, 24 h and 48 h after infecting the animals with the giant
      salamander iridovirus (GSIV), respectively. These results suggest that CgsTLR7
      has a conserved gene structure and might play an important role in immune
      regulation against viral infections in the Chinese giant salamander.

PMID- 25754926
TI  - Investigation of the mechanisms of using metal complexation and cellulose
      nanofiber/sodium alginate layer-by-layer coating for retaining anthocyanin
      pigments in thermally processed blueberries in aqueous media.
AB  - This study investigated the mechanisms of anthocyanin pigment retention using
      Fe(3+)-anthocyanin complexation and cellulose nanofiber (CNF)/sodium alginate
      (SA) layer-by-layer (LBL) coatings on thermally processed blueberries in aqueous
      media. Anthocyanin pigments were polymerized through complexation with Fe(3+) but
      readily degraded by heat (93  degrees C for 7 min) in the aqueous media because
      of poor stability. CNF/SA LBL coating was successful to retain anthocyanin
      pigments in thermally processed blueberries. Fruits coated with CNF containing
      CaCl2 followed by treatment in a SA bath formed a second hydrogel layer onto the
      CNF layer (LBL coating system) through cross-linking between Ca(2+) and alginic
      acid. Methyl-cellulose-modified CNF improved the interactions between CNF, the
      fruit surface, and the SA layer. This study demonstrated that the CNF/SA LBL
      coating system was effective to retain anthocyanin pigments on thermally
      processed whole blueberries, whereas no combined benefit of complexation with
      coating was observed. Results explained the mechanisms of the new approaches for
      developing colorful and nutritionally enhanced anthocyanin-rich fruit products. 

PMID- 25754927
TI  - [Microbiological diagnosis of periprosthetic joint infections].
AB  - BACKGROUND: Prosthetic joint infection is a rare but serious complication after
      arthroplasty, leading to prolonged hospitalization and repeated surgical
      intervention. THEME: In this article, successful strategies for the rapid and
      accurate microbiological diagnosis of infection are reviewed. In the case of
      clinical suspicion of a prosthetic joint infection, at least a comprehensive
      clinical review of the patient's postoperative history, a physical examination,
      routine blood tests including white cell count, erythrocyte sedimentation rate,
      and C-reactive protein, and further investigation of the synovial-fluid leukocyte
      count and microbial culture are needed. Depending of the clinical signs of
      infection additional blood culture samples should be taken. RESULTS: The gold
      standard to confirm infection is a surgical procedure with at least 5-6 biopsies
      from suspected areas for both microbial culture and histopathological
      examination. Culture results may be negative because of previous antimicrobial
      therapy, a low number of culturable organisms in biofilm formations,
      inappropriate culture medium, and prolonged transport time. CONCLUSION: In any of
      these conditions, diagnosis with highly sensitive diagnostic techniques such as
      polymerase chain reaction should be considered for the identification of the
      causative agent in order to establish the most appropriate antimicrobial
      treatment options.

PMID- 25754928
TI  - Lanthanide complexes of azidophenacyl-DO3A as new synthons for click chemistry
      and the synthesis of heterometallic lanthanide arrays.
AB  - Lanthanide complexes of azidophenacyl DO3A are effective substrates for click
      reactions with ethyne derivatives, giving rise to aryl triazole appended
      lanthanide complexes, in which the aryl triazole acts as an effective sensitising
      chromophore for lanthanide luminescence. They also undergo click chemistry with
      propargylDO3A derivatives, giving rise to heterometallic complexes. 

PMID- 25754929
TI  - Barriers to Clinical Research Participation Among African Americans.
AB  - Clinical research requires representation of racially and ethnically diverse
      participants to accurately represent the general population. Overall life
      expectancy of African Americans is shorter than that of the general U.S.
      POPULATION: Compared with the other ethnic groups in the United States, African
      Americans have higher rates of hypertension, stroke, obesity, and diabetes, and
      higher rates of mortality related to stroke and cancer. Although many health
      disparities exist among African Americans, they are well underrepresented in
      clinical research. This article provides an overview of barriers that may
      influence participation in clinical research among African Americans. Issues of
      trust, experimentation, communication, and logistics are the most commonly
      identified barriers. The barriers and facilitators identified in this review may
      be useful in the development and implementation of recruitment and research
      strategies that are culturally sensitive and that may enhance trust and
      willingness to participate among African Americans.

PMID- 25754930
TI  - Up-regulation of galectin-9 induces cell migration in human dendritic cells
      infected with dengue virus.
AB  - Galectin-9 (Gal-9) exerts immunosuppressive effects by inducing apoptosis in T
      cells that produce interferon-gamma and interleukin (IL)-17. However, Gal-9 can
      be pro-inflammatory in lipopolysaccharide-stimulated monocytes. Using microarray
      analysis, we observed that Gal-9 was up-regulated in human dendritic cells (DCs)
      after dengue virus (DV) infection. The investigation into the immunomodulatory
      effects and mechanisms of Gal-9 in DCs exposed to DV revealed that DV infection
      specifically increased mRNA and protein levels of Gal-9 but not those of Gal-1 or
      Gal-3. Blocking p38, but not c-Jun N-terminal kinase or extracellular signal
      regulated kinase (ERK), inhibited DV-induced expression of Gal-9. Reduction in
      Gal-9 by small interference RNA treatment suppressed DV-stimulated migration of
      DCs towards the chemoattractants CCL19 and CCL21. In addition, DV-induced IL
      12p40 production was reduced after knockdown of Gal-9 in DCs. Furthermore, Gal-9
      deficiency suppressed DV-induced activation of nuclear factor-kappaB. Inhibition
      of DV-induced DC migration under conditions of Gal-9 deficiency was mediated
      through suppressing ERK activation but not by regulating the expression of CCR7,
      the receptor for CCL19 and CCL21. Both the reduction in IL-12 production and the
      suppression of ERK activity might account for the inhibition of DV-induced DC
      migration after knockdown of Gal-9. In summary, this study reveals the roles of
      Gal-9 in DV-induced migration of DCs. The findings indicate that Gal-9 might be a
      therapeutic target for preventing immunopathogenesis induced by DV infection. 

PMID- 25754931
TI  - Family members' experiences of keeping a diary during a sick relative's stay in
      the intensive care unit: a hermeneutic interview study.
AB  - OBJECTIVE: The aim of the study was to explore family members' experiences with
      keeping a diary during a sick relative's stay in the ICU. DESIGN: A qualitative
      method with a hermeneutic approach was used. Eleven participants, who recorded
      nine diaries in total, were interviewed. The collected data were analysed using a
      hermeneutic approach inspired by Gadamer. RESULTS: The analysis revealed a meta
      theme: 'it [writing in the diary] felt like contact' which was created by a
      feeling of togetherness and the opportunity to communicate with the patient.
      Keeping a diary likely meets the needs of family members in several ways because
      it becomes a way to be present at the patient's bedsides, to provide caregiving,
      to maintain hope and to relay cogent information. However, concerns regarding
      negative aspects of diary keeping were also raised; for example, the diary
      created feelings of stress, guilt and failure and exposed intimate details.
      CONCLUSION: The diary symbolised the maintenance of relationships with the
      patients and was a substitute for the usual opportunities for communication.
      Furthermore, it was instrumental in meeting the needs of the majority of family
      members in several ways. Nevertheless, the diary did have negative effects for
      certain individuals, which highlights the importance of an individualised
      approach.

PMID- 25754932
TI  - Abrupt thrombocytopenia with sustained trilineage engraftment in a stem cell
      transplant recipient.

PMID- 25754934
TI  - Classification of the spermatogenic cycle, seasonal changes of seminiferous
      tubule morphology and estimation of the breeding season of the large Japanese
      field mouse (Apodemus speciosus) in Toyama and Aomori prefectures, Japan.
AB  - The large Japanese field mouse, Apodemus speciosus, is a potential indicator of
      environmental stress, but this function has not been confirmed by histological
      studies. Since environmental stress affects the reproductive function of mice, we
      determined the reproductive characteristics of this species at two locations:
      Toyama (36 degrees 35'N, 137 degrees 24'E) and Aomori (40 degrees 35'N, 140
      degrees 57'E). Mice were captured during May-November (n=119) and July-November
      (n=146) at these locations, respectively. We classified the breeding season from
      the numbers of pregnant females and young, in addition to the spermatogenic cycle
      and seasonal changes in seminiferous tubule morphology of males. Testicular
      weight was measured, and seminiferous tubule morphology was examined
      histologically. Fourteen stages were found in the seminiferous epithelium cycle
      based on acrosome formation and spermatid head morphology. At both locations, the
      breeding season peaked from late summer to early autumn and possibly in spring.
      Spermatogenic activity was classified into 4 periods from June to November:
      resting around June and October-November; resumptive around July; active around
      August; and degenerative around September. During the resting period, the
      seminiferous tubules consisted of Sertoli cells, spermatogonia and spermatocytes.
      Spermatogenesis began during the resumptive period, and spermatids were observed.
      During the active period, active spermatogenesis and a broad lumen were observed.
      During the degenerative period, spermatogenesis ended, and Sertoli cells,
      spermatogonia, spermatocytes and degenerating exfoliated round spermatids were
      observed. This study provides scientific information about the testicular
      histopathological evaluations of the large Japanese field mouse for its use as an
      index species of environmental pollution. 

PMID- 25754933
TI  - ICOS is required for the generation of both central and effector CD4(+) memory T
      cell populations following acute bacterial infection.
AB  - Interactions between ICOS and ICOS ligand (ICOSL) are essential for the
      development of T follicular helper (Tfh) cells and thus the formation and
      maintenance of GC reactions. Given the conflicting reports on the requirement of
      other CD4(+) T-cell populations for ICOS signals, we have employed a range of in
      vivo approaches to dissect requirements for ICOS signals in mice during an
      endogenous CD4(+) T-cell response and contrasted this with CD28 signals. Genetic
      absence of ICOSL only modestly reduced the total number of antigen-specific
      CD4(+) T cells at the peak of the primary response, but resulted in a severely
      diminished number of both T central memory and T effector memory cells. Treatment
      with blocking anti-ICOS mAb during the primary response recapitulated these
      effects and caused a more substantial reduction than blocking CD28 signals with
      CTLA4Ig. During the memory phase of the response further signals through ICOS or
      CD28 were not required for survival. However, upon secondary challenge only Tfh
      cell expansion remained heavily ICOS-dependent, while CD28 signals were required
      for optimal expansion of all subsets. These data demonstrate the importance of
      ICOS signals specifically for memory CD4(+) T-cell formation, while highlighting
      the potential of therapeutically targeting this pathway. 

PMID- 25754935
TI  - Detection of Escherichia albertii from chicken meat and giblets.
AB  - Escherichia albertii occasionally causes food-borne outbreaks of gastroenteritis
      in humans; however, little is known about the vehicle of transmission. To screen
      retail chicken products for the presence of E. albertii, 104 retail chicken
      products were investigated. Portions of enrichment cultures that were PCR
      positive for E. albertii (n=3) were sub-cultured on agar medium. Only 2 strains
      obtained from 2 chicken giblet samples were identified as E. albertii by multi
      locus sequence typing. Antimicrobial susceptibility testing showed that 1 strain
      was resistant to streptomycin and sulfisoxazole. Both strains harbored the
      virulence genes cdt and eae. This study is the first description of E. albertii
      isolation from retail food, suggesting that chicken products are a potential
      vehicle of E. albertii transmission. 

PMID- 25754936
TI  - Structural quality indicators to support quality of care for older people with
      cognitive impairment in emergency departments.
AB  - OBJECTIVES: The purpose of this study was to identify the structural quality of
      care domains and to establish a set of structural quality indicators (SQIs) for
      the assessment of care of older people with cognitive impairment in emergency
      departments (EDs). METHODS: A structured approach to SQI development was
      undertaken including: 1) a comprehensive search of peer-reviewed and gray
      literature focusing on identification of evidence-based interventions targeting
      structure of care of older patients with cognitive impairment and existing SQIs;
      2) a consultative process engaging experts in the care of older people and
      epidemiologic methods (i.e., advisory panel) leading to development of a draft
      set of SQIs; 3) field testing of drafted SQIs in eight EDs, leading to refinement
      of the SQI set; and 4) an independent voting process among the panelists for SQI
      inclusion in a final set, using preestablished inclusion and exclusion criteria.
      RESULTS: At the conclusion of the process, five SQIs targeting the management of
      older ED patients with cognitive impairment were developed: 1) the ED has a
      policy outlining the management of older people with cognitive impairment during
      the ED episode of care; 2) the ED has a policy outlining issues relevant to
      carers of older people with cognitive impairment, encompassing the need to
      include the (family) carer in the ED episode of care; 3) the ED has a policy
      outlining the assessment and management of behavioral symptoms, with specific
      reference to older people with cognitive impairment; 4) the ED has a policy
      outlining delirium prevention strategies, including the assessment of patients'
      delirium risk factors; and 5) the ED has a policy outlining pain assessment and
      management for older people with cognitive impairment. CONCLUSIONS: This article
      presents a set of SQIs for the evaluation of performance in caring for older
      people with cognitive impairment in EDs.

PMID- 25754937
TI  - Process quality indicators targeting cognitive impairment to support quality of
      care for older people with cognitive impairment in emergency departments.
AB  - OBJECTIVES: The objective of this study was to develop process quality indicators
      (PQIs) to support the improvement of care services for older people with
      cognitive impairment in emergency departments (ED). METHODS: A structured
      research approach was taken for the development of PQIs for the care of older
      people with cognitive impairment in EDs, including combining available evidence
      with expert opinion (phase 1), a field study (phase 2), and formal voting (phase
      3). A systematic review of the literature identified ED processes targeting the
      specific care needs of older people with cognitive impairment. Existing relevant
      PQIs were also included. By integrating the scientific evidence and clinical
      expertise, new PQIs were drafted and, along with the existing PQIs, extensively
      discussed by an advisory panel. These indicators were field tested in eight
      hospitals using a cohort of older persons aged 70 years and older. After analysis
      of the field study data (indicator prevalence, variability across sites), in a
      second meeting, the advisory panel further defined the PQIs. The advisory panel
      formally voted for selection of those PQIs that were most appropriate for care
      evaluation. RESULTS: In addition to seven previously published PQIs relevant to
      the care of older persons, 15 new indicators were created. These 22 PQIs were
      then field tested. PQIs designed specifically for the older ED population with
      cognitive impairment were only scored for patients with identified cognitive
      impairment. Following formal voting, a total of 11 PQIs were included in the set.
      These PQIs targeted cognitive screening, delirium screening, delirium risk
      assessment, evaluation of acute change in mental status, delirium etiology, proxy
      notification, collateral history, involvement of a nominated support person, pain
      assessment, postdischarge follow-up, and ED length of stay. CONCLUSIONS: This
      article presents a set of PQIs for the evaluation of the care for older people
      with cognitive impairment in EDs. The variation in indicator triggering across
      different ED sites suggests that there are opportunities for quality improvement
      in care for this vulnerable group. Applied PQIs will identify an emergency
      services' implementation of care strategies for cognitively impaired older ED
      patients. Awareness of the PQI triggers at an ED level enables implementation of
      targeted interventions to improve any suboptimal processes of care. Further
      validation and utility of the indicators in a wider population is now indicated.

PMID- 25754938
TI  - Agreeableness and Self-Consciousness as Predictors of Induced Scratching and Itch
      in Patients with Psoriasis.
AB  - BACKGROUND: Psoriasis (PS) is a frequent skin disease accompanied by itch, a
      symptom that has been shown to be related to depression and self-consciousness.
      PS patients describe themselves as more agreeable than healthy controls (HC), a
      trait that might be protective against impulsive scratching. PURPOSE: This study
      is the first to analyze the relationship between agreeableness and induced
      scratching and between depression, self-consciousness, and induced itch in PS
      patients. METHODS: Twenty-four PS patients and 24 HC were shown two videos: an
      itch-inducing experimental video (EV) and a non-itch-inducing control video (CV).
      Induced itch/scratching was determined by calculating the difference in itch
      intensity/number of scratch movements between EV and CV. Validated questionnaires
      were used to measure agreeableness, depression, and self-consciousness. RESULTS:
      In accordance with our hypothesis, in PS patients, public self-consciousness was
      significantly positively associated with induced itch (r = 0.564; p < 0.001), and
      agreeableness was significantly negatively associated with induced scratching (r
      = -0.444; p < 0.05). In HC, the relationship between public self-consciousness
      and induced itch and between agreeableness and induced scratching were positive,
      but not significant. CONCLUSIONS: This study showed distinct findings for PS
      patients and HC regarding the relationship between agreeableness and induced
      scratching. The relationship between public self-consciousness and induced itch
      was positive in both groups. The distinct finding regarding agreeableness
      supports the idea that scoring low on this scale might be a protective factor for
      scratching in PS patients. Future research should investigate mediating factors
      of the outlined relationships.

PMID- 25754940
TI  - Expression, receptor binding, and biophysical characterization of guinea pig
      insulin desB30: a monomeric insulin variant.
AB  - Here we report, for the first time, the heterologous expression of desB30 guinea
      pig insulin (GI desB30) in the yeast Saccharomyces cerevisiae. The affinities of
      GI desB30 for the insulin receptor A and the IGF-I receptor were also quantified
      for the first time. Small-angle X-ray scattering and analytical
      ultracentrifugation studies confirmed that GI desB30 did not form dimers or
      hexamers, in contrast to human insulin. Size-exclusion chromatography connected
      to inductively coupled plasma mass spectrometry revealed that GI desB30 has
      affinity towards several divalent metal ions. These studies did not indicate the
      formation of any larger structures of GI desB30 in the presence of various
      divalent metal ions, but did indicate that GI desB30 has an affinity towards Mn,
      Co, and Cu ions. Finally, the low affinity for the insulin receptor and the very
      low affinity for the IGF-I receptor by GI desB30 were quantified.

PMID- 25754939
TI  - Promethazine use among chronic pain patients.
AB  - BACKGROUND: Concomitant use of opioids and promethazine has been reported in
      various subpopulations, including methadone maintenance patients, injection drug
      users, and at-risk teenagers. Promethazine is thought to potentiate the "high"
      from opioids. However, to date, the prevalence of promethazine use has not been
      determined among patients prescribed opioids for chronic pain. METHODS: Urine
      samples from 921 patients prescribed opioids for chronic pain were analyzed for
      promethazine. Demographic data, toxicology results, and opioid prescription
      information were obtained through medical record abstraction. We assessed the
      prevalence and factors associated with promethazine use with bivariable and
      multivariable statistics. RESULTS: The prevalence of promethazine-positive urine
      samples among chronic pain patients was 9%. Only 50% of promethazine-positive
      patients had an active prescription for promethazine. Having benzodiazepine
      positive urine with no prescription for a benzodiazepine was statistically
      associated with promethazine use. Also, having a prescription for methadone for
      pain or being in methadone maintenance for the treatment of opioid dependence
      were both statistically associated with promethazine use. Chronic pain patients
      prescribed only a long-acting opioid were more likely to have promethazine
      positive urines than patients prescribed a short-acting opioid. CONCLUSIONS: The
      study provides compelling evidence of significant promethazine use in chronic
      pain patients. Promethazine should be considered as a potential drug of abuse
      that could cause increased morbidity in opioid-using populations.

PMID- 25754941
TI  - Neck muscle activity in skydivers during parachute opening shock.
AB  - This observational study investigated skydiver neck muscle activity during
      parachute opening shock (POS), as epidemiological data recently suggested neck
      pain in skydivers to be related to POS. Twenty experienced skydivers performed
      two terminal velocity skydives each. Surface electromyography quantified muscle
      activity bilaterally from the anterior neck, the upper and lower posterior neck,
      and the upper shoulders; and two triaxial accelerometers sampled deceleration.
      Muscle activity was normalized as the percentage of reference maximum voluntary
      electrical activity (% MVE); and temporal muscle activity onset was related to
      POS onset. Our results showed that neck muscle activity during POS reached mean
      magnitudes of 53-104% MVE, often exceeding reference activity in the lower
      posterior neck and upper shoulders. All investigated muscle areas' mean temporal
      onsets occurred <50 ms after POS onset (9-34 ms latencies), which is consistent
      with anticipatory motor control. The high muscle activity observed supports that
      the neck is under substantial strain during POS, while temporal muscle activation
      suggests anticipatory motor control to be a strategy used by skydivers to protect
      the cervical spine from POS. This study's findings contribute to understanding
      the high rates of POS-related neck pain, and further support the need for
      evaluation of neck pain preventative strategies.

PMID- 25754942
TI  - Challenges in magnetic resonance imaging for suspected acute appendicitis in
      pregnant patients.
AB  - The assessment of a gravid patient with abdominal pain is a clinical challenge,
      as one must consider not only the common etiologies for abdominal pain but also
      etiologies resulting from the pregnancy. Further complicating the assessment is
      the altered anatomy and physiology that result from the enlarged uterus
      displacing and compressing normal anatomical structures. This alteration of
      anatomy makes the symptoms of appendicitis more variable and thus the diagnosis
      more difficult. Appropriate and timely imaging can result in better patient
      outcomes, and when appendicitis is suspected, imaging investigation should not be
      delayed. This article reviews some of the challenges of magnetic resonance
      imaging in gravid patients with suspected appendicitis and presents strategies
      for imaging this population. 

PMID- 25754944
TI  - Comparing the efficacy and safety between robotic-assisted versus open
      pyeloplasty in children: a systemic review and meta-analysis.
AB  - OBJECTIVE: This manuscript is mainly to systemically review the published reports
      that compared the efficacy and safety of robotic-assisted (RP) versus open
      pyeloplasty (OP) in children with ureteropelvic junction obstruction (UPJO).
      METHODS: We did a systemic search in the PubMed((r)) for all randomized
      controlled trials or comparative studies that compared the surgical results of
      robotic versus open pyeloplasty in children with UPJO. Two of the authors (Hsu
      and Chang) independently did the literature search, quality assessment, and data
      extraction. The obtained data were analyzed with Cochrane Collaboration Review
      Manager (RevMan((r)), version 5.3). The end points of the analysis and review
      included age, operative time, hospital stay, costs, complications, and success
      rate. RESULTS: In total, seven comparative trials and three studies using
      national database met the criteria that comprised 20,691 (RP:OP = 1956:18,735)
      patients in the meta-analysis. Most studies reported median value of patient age,
      operative time, and hospital stay. Only a small proportion of studies could be
      included for meta-analysis. The enrolled trials revealed that RP was more
      frequently performed in older children, required longer operative time, and
      shorter hospital stay. The postoperative success rate was comparable (RR = 0.99,
      95 CI 0.94-1.04). Comparing with OP, there was a significant higher complication
      rate (RR = 1.29, 95 CI 1.10-1.51) and higher costs in the RP group. CONCLUSION:
      Robotic-assisted pyeloplasty may be a promising alternative minimal invasive
      surgery for UPJO in children if the higher complication rates and higher costs in
      the RP can be overcome in the near future.

PMID- 25754945
TI  - Genetic screening in patients with Retinoblastoma in Israel.
AB  - Retinoblastoma (Rb) is a childhood tumor (~1 in 20,000 live births) developing in
      the retina due to mutations in the RB1 gene. Identification of the oncogenic
      mutations in the RB1 gene is important for the clinical management and for
      genetic counseling to families with a child or a parent affected with the tumor.
      Here we present our experience in detecting the pathogenic mutations in blood
      samples, from 150 unrelated Rb patients and highlight the relevant counseling
      issues. Mutation screening in the RB1 gene was based on Sanger sequencing,
      mosaicism of recurrent CpG transition mutations was detected by allele specific
      PCR and multiplex ligation dependent probe amplification for detecting of large
      deletions/duplications. The overall detection rate of mutations in our cohort was
      55% (82/150). In the familial cases it was 100% (17/17), in bilateral and
      unilateral-multifocal sporadic cases 91% (50/55), and in the unilateral sporadic
      cases 19% (15/78). Nonsense mutations and small deletions or insertions that
      results in transcripts with premature termination codons that are subject to
      nonsense mediated decay were the most frequent, detected in 50/82 (61%) of the
      patients. The rest were large deletions detected in 14/82 (17%), splice site
      mutations detected in 11/82 (13%), missense mutations in four patients and
      mutations in the promoter sequence in three patients. Mutation mosaicism ranging
      from 10 to 30% was detected by allele specific PCR in ten patients, 9% (5/55) of
      patients with bilateral tumor and 33% (5/15) of the patients with unilateral
      tumor. In three patients rare variants were detected as the only finding which
      was also detected in other healthy family members. Allele specific amplification
      of recurrent mutations raises in our cohort the identification rate from 82 to
      91% in the sporadic bilateral cases and from 13 to 19% in the unilateral sporadic
      cases. Most mosaic cases could not be identified by Sanger sequencing and
      therefore screening for recurrent CpG transition mutations by allele specific
      amplification is of utmost importance. Molecular screening is important for the
      genetic counseling regarding the risk for tumor development and the relevance for
      prenatal diagnosis but in several families is accompanied by detecting rare
      variants that might be rare polymorphisms or low penetrant mutations.

PMID- 25754946
TI  - Region sampling for robust and rapid autofocus in microscope.
AB  - This paper proposes a region sampling based autofocus method for rapid and robust
      autofocus in microscope. Image content and region size are considered in region
      sampling criteria. An intelligent search algorithm which employs quartering hill
      climbing search and golden section search is developed, in which rule-based
      evaluation of sampled focusing regions is applied. Experimental results
      demonstrate that the proposed method can significantly improve the performance of
      image-based autofocus.

PMID- 25754947
TI  - Arterial spin labeled perfusion imaging using three-dimensional turbo spin echo
      with a distributed spiral-in/out trajectory.
AB  - PURPOSE: The three-dimensional (3D) spiral turbo spin echo (TSE) sequence is one
      of the preferred readout methods for arterial spin labeled (ASL) perfusion
      imaging. Conventional spiral TSE collects the data using a spiral-out readout on
      a stack of spirals trajectory. However, it may result in suboptimal image quality
      and is not flexible in protocol design. The goal of this study is to provide a
      more robust readout technique without such limitation. METHODS: The proposed
      technique incorporates a spiral-in/out readout into 3D TSE, and collects the data
      on a distributed spirals trajectory. The data set is split into the spiral-in and
      -out subsets that are reconstructed separately and combined after image
      deblurring. RESULTS: The volunteer results acquired with the proposed technique
      show no geometric distortion or signal pileup, as is present with GRASE, and no
      signal loss, as is seen with conventional spiral TSE. Examples also demonstrate
      the flexibility in changing the imaging parameters to satisfy various criteria.
      CONCLUSION: The 3D TSE with a distributed spiral-in/out trajectory provides a
      robust readout technique and allows for easy protocol design, thus is a promising
      alternative to GRASE or conventional spiral TSE for ASL perfusion imaging.

PMID- 25754948
TI  - Evaluation of plutonium(IV) extraction rate between nitric acid and tri-n
      butylphosphate solution using a glass chip microchannel.
AB  - Extraction of Pu(IV) with tri-n-butylphosphate is performed using a glass chip
      microchannel to evaluate the extraction rate. Two-phase flow forms in the
      microchannel by introducing a solution of Pu(IV) and tri-n-butylphosphate with
      flow rates above 5 MUL/min. The Pu(IV) extraction reaction proceeds at the
      interface between the two phases. To evaluate the extraction rate, the contact
      time between the two phases is varied from 0.48 to 4.8 s by changing the
      confluent length of the microchannel and the flow rate. The Pu concentration of
      each phase collected from the microchannel is measured with an alpha liquid
      scintillation counter, and the contact time dependence of Pu(IV) extraction is
      obtained. An extraction model based on diffusion in the microchannel and the
      reaction at the interface is proposed and applied to determine the extraction
      rate. The extraction process is assumed to follow pseudo-first-order kinetics,
      and the extraction rate constant of Pu(IV) is determined to be 1.5 * 10(-2) cm/s.
      The investigation demonstrates that a microfluidic device can be a new tool to
      determine Pu(IV) extraction rates. 

PMID- 25754949
TI  - Patient-reported outcomes as end points and outcome indicators in solid tumours.
AB  - Patient-reported outcome (PRO) measures, such as quality of life, have been
      associated with relevant clinical end points and are prognostic for survival
      outcomes in a variety of solid cancers in adults. In the past few years, PROs
      have garnered a greater influence as established and clinically relevant measures
      that could alter the current paradigm of practice-changing therapeutic advances,
      as it has been recognized that classic clinical end points do not accurately
      portray a full appreciation of the benefits, risks and costs of therapy. In this
      Review, we comprehensively assess the correlation of PROs with treatment response
      and survival, and explore tumour-related and patient-centric composite end points
      in patients with cancer participating in clinical trials. Comparisons or
      composite end points that consider tumour-related and PRO components might help
      health-care providers, patients with cancer and decision makers to better
      understand the total clinical benefit of therapeutic interventions.

PMID- 25754950
TI  - Haematological cancer: BCL-ABL1 resistance mutation--breakthrough with axitinib.

PMID- 25754951
TI  - CNS cancer: Visualizing secrets of glioma.

PMID- 25754956
TI  - Histamine H3 receptor in primary mouse microglia inhibits chemotaxis,
      phagocytosis, and cytokine secretion.
AB  - Histamine is a physiological amine which initiates a multitude of physiological
      responses by binding to four known G-protein coupled histamine receptor subtypes
      as follows: histamine H1 receptor (H1 R), H2 R, H3 R, and H4 R. Brain histamine
      elicits neuronal excitation and regulates a variety of physiological processes
      such as learning and memory, sleep-awake cycle and appetite regulation.
      Microglia, the resident macrophages in the brain, express histamine receptors;
      however, the effects of histamine on critical microglial functions such as
      chemotaxis, phagocytosis, and cytokine secretion have not been examined in
      primary cells. We demonstrated that mouse primary microglia express H2 R, H3 R,
      histidine decarboxylase, a histamine synthase, and histamine N-methyltransferase,
      a histamine metabolizing enzyme. Both forskolin-induced cAMP accumulation and ATP
      induced intracellular Ca(2+) transients were reduced by the H3 R agonist imetit
      but not the H2 R agonist amthamine. H3 R activation on two ubiquitous second
      messenger signalling pathways suggests that H3 R can regulate various microglial
      functions. In fact, histamine and imetit dose-dependently inhibited microglial
      chemotaxis, phagocytosis, and lipopolysaccharide (LPS)-induced cytokine
      production. Furthermore, we confirmed that microglia produced histamine in the
      presence of LPS, suggesting that H3 R activation regulate microglial function by
      autocrine and/or paracrine signalling. In conclusion, we demonstrate the
      involvement of histamine in primary microglial functions, providing the novel
      insight into physiological roles of brain histamine.

PMID- 25754958
TI  - Inhibition of PAI-1 Via PAI-039 Improves Dermal Wound Closure in Diabetes.
AB  - Diabetes impairs the ability to heal cutaneous wounds, leading to
      hospitalization, amputations, and death. Patients with diabetes experience
      elevated levels of plasminogen activator inhibitor 1 (PAI-1), regardless of their
      glycemic control. It has been demonstrated that PAI-1-deficient mice exhibit
      improved cutaneous wound healing, and that PAI-1 inhibition improves skeletal
      muscle repair in mice with type 1 diabetes mellitus, leading us to hypothesize
      that pharmacologically mediated reductions in PAI-1 using PAI-039 would normalize
      cutaneous wound healing in streptozotocin (STZ)-induced diabetic (STZ-diabetic)
      mice. To simulate the human condition of variations in wound care, wounds were
      aggravated or minimally handled postinjury. Following cutaneous injury, PAI-039
      was orally administered twice daily for 10 days. Compared with nondiabetic mice,
      wounds in STZ-diabetic mice healed more slowly. Wound site aggravation
      exacerbated this deficit. PAI-1 inhibition had no effect on dermal collagen
      levels or wound bed size. PAI-039 treatment failed to improve angiogenesis in the
      wounds of STZ-diabetic mice and blunted angiogenesis in the wounds of nondiabetic
      mice. Importantly, PAI-039 treatment significantly improved epidermal cellular
      migration and wound re-epithelialization compared with vehicle-treated STZ
      diabetic mice. These findings support the use of PAI-039 as a novel therapeutic
      agent to improve diabetic wound closure and demonstrate the primary mechanism of
      its action to be related to epidermal closure. 

PMID- 25754957
TI  - Adaptation of beta-Cell and Endothelial Function to Carbohydrate Loading:
      Influence of Insulin Resistance.
AB  - High-carbohydrate diets have been associated with beta-cell strain, dyslipidemia,
      and endothelial dysfunction. We examined how beta-cell and endothelial function
      adapt to carbohydrate overloading and the influence of insulin resistance. On
      sequential days in randomized order, nondiabetic subjects (classified as insulin
      sensitive [IS] [n = 64] or insulin-resistant [IR] [n = 79] by euglycemic clamp)
      received four mixed meals over 14 h with either standard (300 kcal) or double
      carbohydrate content. beta-Cell function was reconstructed by mathematical
      modeling; brachial artery flow-mediated dilation (FMD) was measured before and
      after each meal. Compared with IS, IR subjects showed higher glycemia and insulin
      hypersecretion due to greater beta-cell glucose and rate sensitivity;
      potentiation of insulin secretion, however, was impaired. Circulating free fatty
      acids (FFAs) were less suppressed in IR than IS subjects. Baseline FMD was
      reduced in IR, and postprandial FMD attenuation occurred after each meal,
      particularly with high carbohydrate, similarly in IR and IS. Throughout the two
      study days, higher FFA levels were significantly associated with lower (incretin
      induced) potentiation and impaired FMD. In nondiabetic individuals, enhanced
      glucose sensitivity and potentiation upregulate the insulin secretory response to
      carbohydrate overloading. With insulin resistance, this adaptation is impaired.
      Defective suppression of endogenous FFA is one common link between impaired
      potentiation and vascular endothelial dysfunction. 

PMID- 25754959
TI  - Evaluation of the Effect of Enteral Lipid Sensing on Endogenous Glucose
      Production in Humans.
AB  - Administration of lipids into the upper intestine of rats has been shown to
      acutely decrease endogenous glucose production (EGP) in the preabsorptive state,
      postulated to act through a gut-brain-liver axis involving accumulation of long
      chain fatty acyl-CoA, release of cholecystokinin, and subsequent neuronal
      signaling. It remains unknown, however, whether a similar gut-brain-liver axis is
      operative in humans. Here, we infused 20% Intralipid (a synthetic lipid emulsion)
      or saline intraduodenally for 90 min at 30 mL/h, 4 to 6 weeks apart, in random
      order, in nine healthy men. EGP was assessed under pancreatic clamp conditions
      with stable isotope enrichment techniques. Under these experimental conditions,
      intraduodenal infusion of Intralipid, compared with saline, did not affect plasma
      glucose concentration or EGP throughout the study period. We conclude that
      Intralipid infusion into the duodenum at this rate does not elicit detectable
      effects on glucose homeostasis or EGP in healthy men, which may reflect important
      interspecies differences between rodents and humans with respect to the putative
      gut-brain-liver axis. 

PMID- 25754960
TI  - Attenuation of neuromotor deficits by natural antioxidants of Decalepis
      hamiltonii in transgenic Drosophila model of Parkinson's disease.
AB  - Oxidative stress is believed to be a major factor for the onset of Parkinson's
      disease (PD). In this study, we have investigated oxidative status in transgenic
      Drosophila model of PD. Our results revealed elevated levels of reactive oxygen
      species (ROS) and lipid peroxidation (LPO) in A30P and A53T alpha-synuclein PD
      model flies compared to control. We have demonstrated for the first time the
      ameliorating potential of natural antioxidants characterized from the roots of Dh
      in A30P and A53T alpha-synuclein PD model flies. Feeding of transgenic flies with
      aqueous Dh root extract for 21 days significantly improved their climbing ability
      and circadian rhythm of locomotor activity which was associated with reduction in
      levels of ROS and LPO and enhancement in the activities of catalase (CAT) and
      superoxide dismutase (SOD). Dh protected against paraquat (PQ) sensitivity in
      alpha-synuclein transgenic flies and delayed the onset of PD-like symptoms which
      appears to be mediated by suppression of oxidative stress.

PMID- 25754962
TI  - Pedestrian injury patterns and risk in minibus collisions in China.
AB  - BACKGROUND: The minibus, with a nearly flat front, is widely used in China,
      especially in the underdeveloped regions, and results in large numbers of
      pedestrian injuries and deaths. The purpose of this study was to determine the
      injury patterns and risk for pedestrians involved in these crashes. MATERIAL AND
      METHODS: We conducted an in-depth investigation of minibus/pedestrian accidents
      in Chongqing, China, occurring between September 2000 and April 2014. The
      enrolled pedestrians was classified into 3 groups: young (aged 14-44 years),
      middle-aged (aged 45-59 years), and elderly (aged over 60 years). Pedestrian
      injuries were coded according to the Abbreviated Injury Scale (AIS). RESULTS: A
      total of 109 pedestrians, with an average age of 55.7+/-16.2 years, were injured
      or killed--30.3% were young, 23.9% were middle-aged, and 45.9% were elderly.
      Pedestrians hit by a minibus had a high proportion of head, chest, and extremity
      injuries--84.4%, 50.5%, and 52.3%, respectively. In addition, impact speeds in
      excess of 75 km/h all ultimately resulted in fatalities. At an impact speed of 30
      km/h, the risk of pedestrian fatality and AIS3+ injury are approximately 12.0%
      and 37.2%, respectively. At 50 km/h the risks are 65.2% and 96.9%, respectively,
      and at 70 km/h the risks are 96.3% and 99.9%, respectively. CONCLUSIONS: A higher
      likelihood of chest injury was associated with being older and impact speed of
      over 40 km/h in minibus/pedestrian collision. Our data suggest that the injury
      patterns of pedestrians in minibus collisions differ from that in other
      vehicle/pedestrian collisions. These findings could contribute to better
      understanding of the injury patterns and risk of pedestrian in minibus collisions
      in China, which may play an important role in developing measures to improve
      traffic safety.

PMID- 25754963
TI  - Risk factors for prolonged mechanical ventilation for children on ventricular
      assist device support.
AB  - BACKGROUND: Patients with end-stage heart failure possess many attributes that
      place them at risk for prolonged mechanical ventilation (MV). However, there are
      only limited data on MV support among children after ventricular assist device
      (VAD) implantation. We report the duration of MV after VAD placement, indications
      for respiratory support in the postimplantation period, and associated patient
      factors. METHODS: This single-center retrospective study included 43 consecutive
      children (aged <18 years) with end-stage heart failure who were supported with a
      VAD as a bridge to transplantation from January 2005 to December 2011.
      Multivariable analysis was performed using the multiple Poisson regression model
      for the duration of MV. RESULTS: Overall, 33% (n = 14) remained on MV until heart
      transplant or death. Of those requiring pre-VAD extracorporeal membrane
      oxygenation (ECMO) support, 63% (n = 12 of 19) remained on MV until heart
      transplant or death compared with 8% (n = 2 of 24) among those not on ECMO before
      VAD (p < 0.001). Patients with moderate or severe mitral regurgitation while on
      VAD support had 1.7-times more MV days compared with those with none or trivial
      on-VAD mitral regurgitation. In addition, previous support on ECMO, those with
      moderate or severe tricuspid regurgitation, and those with only left VAD implants
      had an increased risk of prolonged MV. CONCLUSIONS: Our results suggest that VAD
      recipients previously supported on ECMO, those with moderate or severe mitral
      regurgitation, moderate or severe tricuspid regurgitation, and those with only
      left VAD implants had an increased risk of prolonged MV. Future studies in larger
      cohorts are necessary to confirm the findings from this single-institutional
      experience.

PMID- 25754961
TI  - Coordinated interaction of Down syndrome cell adhesion molecule and deleted in
      colorectal cancer with dynamic TUBB3 mediates Netrin-1-induced axon branching.
AB  - Modulation of actin and microtubule (MT) dynamics in neurons is implicated in
      guidance cue-dependent axon outgrowth, branching and pathfinding. Although the
      role of MTs in axon guidance has been well known, how extracellular guidance
      signals engage MT behavior in axon branching remains unclear. Previously, we have
      shown that TUBB3, the most dynamic beta-tubulin isoform in neurons, directly
      binds to deleted in colorectal cancer (DCC) to regulate MT dynamics in Netrin-1
      mediated axon guidance. Here, we report that TUBB3 directly interacted with
      another Netrin-1 receptor Down syndrome cell adhesion molecule (DSCAM) and Netrin
      1 increased this interaction in primary neurons. MT dynamics were required for
      Netrin-1-promoted association of DSCAM with TUBB3. Knockdown of either DSCAM or
      DCC or addition of a function blocking anti-DCC antibody mutually blocked Netrin
      1-induced interactions, suggesting that DSCAM interdependently coordinated with
      DCC in Netrin-1-induced binding to TUBB3. Both DSCAM and DCC were partially
      colocalized with TUBB3 in the axon branch and the axon branching point of primary
      neurons and Netrin-1 increased these colocalizations. Netrin-1 induced the
      interaction of endogenous DSCAM with polymerized TUBB3 in primary neurons and Src
      family kinases (SFKs) were required for regulating this binding. Knockdown of
      DSCAM only, DCC only or both was sufficient to block Netrin-1-induced axon
      branching of E15 mouse cortical neurons. Knocking down TUBB3 inhibited Netrin-1
      induced axon branching as well. These results suggest that DSCAM collaborates
      with DCC to regulate MT dynamics via direct binding to dynamic TUBB3 in Netrin-1
      induced axon branching. 

PMID- 25754964
TI  - Comparison of 30-Day Outcomes of Transfemoral Versus Transapical Approach for
      Transcatheter Aortic Valve Replacement: A Single-Center US Experience.
AB  - BACKGROUND: The optimal access route for transcatheter aortic valve replacement
      (TAVR) remains debatable. We compared early safety outcomes at 30 days between
      the transfemoral (TF) and transapical (TA) approaches in a single, high-volume
      center in the United States. METHODS: Data were collected retrospectively on
      consecutive patients who underwent TAVR by the TF or TA approach. The primary
      endpoints included the following: all-cause mortality; stroke; major and life
      threatening bleeding; renal failure; valve-related dysfunction requiring an
      intervention; and moderate to severe paravalvular leak and major vascular
      complications at 30 days. The secondary endpoints included need for a pacemaker
      and hospital length of stay. RESULTS: A total of 123 well-matched patients
      underwent TAVR (TF 66 [54%] and TA 57 [46%]). All-cause mortality at 30 days was
      identical in both groups (TF 4.5% vs TA 5.3%, p = 0.999). The rates of myocardial
      infarction (TF 1.6% vs TA 1.5%, p = 0.999) and stroke (TF 3.0% vs TA 5.3%, p =
      0.662) were similar. Major bleeding, acute renal failure, valve-related
      dysfunction, paravalvular leak, and mean hospital length of stay were also
      similar in both groups. Unplanned vascular complications, fluoroscopy time, and
      contrast utilization were significantly lower in the TA group. CONCLUSIONS: The
      TA approach has similar early safety outcomes when compared with the TF approach.
      The TA approach is more procedurally efficient when compared with the TF
      approach.

PMID- 25754965
TI  - Outcomes of aortic root replacement after previous aortic root replacement: the
      "true" redo root.
AB  - BACKGROUND: Aortic reoperations are technically challenging. This study evaluated
      outcomes after "true" redo root replacement (previous full root replacement)
      stratified by cause of prosthesis failure. METHODS: Data were compared for 793
      patients who underwent a first-time sternotomy (de novo group) and 120 patients
      who had previously undergone full aortic root replacement (redo group), of which
      76 underwent reoperation due to structural valve deterioration (degenerative
      group), and 44 due to endocarditis (infection group). RESULTS: Overall mortality
      was 4% (n = 28) in the de novo group and 5% (n = 6) in the redo group (p = 0.43)
      (degenerative group, 3%, infection group, 9%; p = 0.19). The infection group had
      an increased incidence of renal failure, sternal infection, prolonged
      ventilation, reoperation for bleeding, multisystem failure, and sepsis, and an
      increased hospital length of stay. The degenerative group and the de novo group
      had a similar risk of perioperative death and major complications. The 5-year
      survival was 86.3% +/- 1.3% for the de novo group and 77.3% +/- 4.6% for the redo
      group (p <= 0.01; degenerative, 86.3% +/- 5%; infection, 65.3% +/- 7.7%; p <
      0.01; p = 0.98 for de novo vs degenerative). Multivariate analysis demonstrated
      that reoperation for degenerative failure did not increase the risk of
      perioperative or late death. CONCLUSIONS: Redo aortic root replacement can be
      performed with low perioperative morbidity and death. The presence of infection
      increases the risk of complications and worsens survival. However, redo root
      replacement for degenerative failure can be performed with similar short-term
      complication risk and midterm survival as de novo root replacement.

PMID- 25754966
TI  - Dermatoscopic features of vulval lesions in 97 women.

PMID- 25754967
TI  - Developmental abnormality induced by strong static magnetic field in
      Caenorhabditis elegans.
AB  - Understanding the effects of strong static magnetic fields (SMFs) on living
      organisms is significant in health risk assessment, but underlying mechanisms are
      largely unknown. In the present study, we determined developmental abnormalities
      induced by 8.5Tesla (T) SMFs in a well-established in vivo model organism,
      Caenorhabditis elegans (C. elegans). Exposure of C. elegans eggs to 8.5 T SMF
      resulted in a time-dependent lifespan decrease, whereas only slight changes were
      observed upon exposure to 5 T SMF. Although SMF exposure did not alter brood
      size, development rate and stages were significantly modified by 8.5 T SMF. Germ
      cell apoptosis dramatically increased upon exposure to 8.5 T SMF in adult worms,
      as confirmed by ced-3 and ced-4 mutants, and could be prevented by concurrent
      treatment with a free radical scavenger, dimethyl sulfoxide. Compared to wild
      type worms, shorter lifespan and greater numbers of apoptotic cells were observed
      in abnormal methyl viologen sensitivity-1 (mev-1(kn1)) nematodes with increased
      sensitivity to oxidative damage. Furthermore, exposure to 8.5 T SMF increased
      expression of superoxide dismutase-3 (sod-3), which is thought to protect against
      oxidative stress. However, 8.5 T SMF had minimal effects on lifespans of daf-2
      and daf-16 mutants, which have compromised insulin/IGF-1 (insulin-like growth
      factors-1) mediated signaling pathways; this finding was consistent with the
      expression of these genes in wild-type worms. Our results indicate that
      developmental toxicity induced by strong SMF in C. elegans is mediated by
      oxidative stress and may be regulated by the insulin-like receptor pathway.

PMID- 25754968
TI  - Selective aptamer-based control of intraneuronal signaling.
AB  - Cellular behavior is orchestrated by the complex interactions of a myriad of
      intracellular signal transduction pathways. To understand and investigate the
      role of individual components in such signaling networks, the availability of
      specific inhibitors is of paramount importance. We report the generation and
      validation of a novel variant of an RNA aptamer that selectively inhibits the
      mitogen-activated kinase pathway in neurons. We demonstrate that the aptamer
      retains function under intracellular conditions and that application of the
      aptamer through the patch-clamp pipette efficiently inhibits mitogen-activated
      kinase-dependent synaptic plasticity. This approach introduces synthetic aptamers
      as generic tools, readily applicable to inhibit different components of
      intraneuronal signaling networks with utmost specificity. 

PMID- 25754969
TI  - Liposomal doxorubicin doubly functionalized with CCK8 and R8 peptide sequences
      for selective intracellular drug delivery.
AB  - A new dual-ligand liposomal doxorubicin delivery system, which couples targeting
      to enhanced cellular uptake and may lead to a more efficient drug delivery
      system, is here designed and synthetized. Liposomes based on the composition 1,2
      dioleoyl-sn-glycero-3-phosphocholine/1,2-distearoyl-sn-glycero-3
      phosphoethanolamine-Peg2000-R8/(C18)2-L5-SS-CCK8 (87/8/5 mol/mol/mol) were
      prepared and loaded with doxorubicin. Presence of the two peptides on the
      external surface is demonstrated by fluorescence resonance energy transfer assay.
      The combination of the R8 cell-penetrating peptide and of the CCK8 targeting
      peptide (homing peptide) on the liposome surface is obtained by combining pre
      modification and post-modification methods. In the dual-ligand system, the CCK8
      peptide is anchored to the liposome surface by using a disulfide bond. This
      chemical function is inserted in order to promote the selective cleavage of the
      homing peptide under the reductive conditions expected in proximity of the tumor
      site, thus allowing targeting and internalization of the liposomal drug.

PMID- 25754970
TI  - Epidemiological and etiological characteristics of hand, foot, and mouth disease
      in Henan, China, 2008-2013.
AB  - Hand, foot, and mouth disease (HFMD) is a common childhood illness caused by
      enteroviruses. HFMD outbreaks and reported cases have sharply increased in China
      since 2008. Epidemiological and clinical data of HFMD cases reported in Henan
      Province were collected from 2008 to 2013. Clinical specimens were obtained from
      a subset of these cases. Descriptive epidemiological methods were used to analyze
      the time, region and population distribution. The VP1 gene from EV71 and CA16
      isolates was amplified, and the sequences were analyzed. 400,264 cases of HFMD
      were reported in this study, including 22,309 severe and 141 fatal cases.
      Incidence peaked between April and May. Laboratory confirmation was obtained for
      27,692 (6.9%) cases; EV71, CA16, and other enteroviruses accounted for 59.5%,
      14.1%, 26.4%, respectively. Phylogenetic analysis revealed that EV71 belonged to
      the C4a evolution branch of C4 sub-genotype and CA16 belonged to subtype B1a or
      B1b. The occurrence of HFMD in Henan was closely related to season, age and
      region distribution. Children under five were the most affected population. The
      major pathogens causing HFMD and their genotypes have not notably changed in
      Henan. The data strongly support the importance of EV71 vaccination in a high
      population density area such as Henan, China. 

PMID- 25754971
TI  - Sexual minority specific and related traumatic experiences are associated with
      increased risk for smoking among gay and bisexual men.
AB  - OBJECTIVE: This study examined the hypothesis that sexual minority specific
      stress and trauma histories may explain some of the risk for smoking among
      gay/bisexual men. METHODS: Patients at a Boston community health center were
      invited to complete a 25-item questionnaire assessing demographics, general
      health, trauma history, and substance use. Of the 3103 who responded, 1309
      identified as male and gay or bisexual (82.8% White and mean age of 38.55 [sd =
      9.76]). RESULTS: A multinomial logistic regression with never smoked as referent
      group and covariates of age, education, employment, HIV status, and race, showed
      that the number of sexual minority stressors/traumas were significantly related
      to the odds of both current and former smoking. In comparison to participants
      with no trauma history, those who reported 1, 2, 3, and 4 traumas had
      respectively 1.70 (OR = 1.70: 95% CI: 1.24-2.34), 2.19 (OR = 2.19: 95% CI: 1.48
      3.23), 2.88 (OR = 2.88: 95% CI: 1.71-4.85), and 6.94 (OR = 6.94: 95% CI: 2.62
      18.38) the odds of identifying as a current smoker. Adjusted logistic regression
      analysis revealed a significant dose effect of number of sexual minority
      stressors/traumas with odds of ever smoking. Experiencing intimate partner
      violence, anti-gay verbal attack, anti-gay physical attack, and childhood sexual
      abuse were each independently associated with increased odds of the smoking
      outcomes. CONCLUSION: A sexual minority specific trauma history may represent a
      vulnerability for smoking among gay/bisexual men. Interventions that address
      trauma may enhance the efficacy of smoking cessation programs and improve the
      mental health of gay/bisexual men.

PMID- 25754973
TI  - Brassinosteroids promote development of rice pollen grains and seeds by
      triggering expression of Carbon Starved Anther, a MYB domain protein.
AB  - Transport of photoassimilates from leaf tissues (source regions) to the sink
      organs is essential for plant development. Here, we show that a phytohormone, the
      brassinosteroids (BRs) promotes pollen and seed development in rice by directly
      promoting expression of Carbon Starved Anther (CSA) which encodes a MYB domain
      protein. Over-expression of the BR-synthesis gene D11 or a BR-signaling factor
      OsBZR1 results in higher sugar accumulation in developing anthers and seeds, as
      well as higher grain yield compared with control non-transgenic plants.
      Conversely, knockdown of D11 or OsBZR1 expression causes defective pollen
      maturation and reduced seed size and weight, with less accumulation of starch in
      comparison with the control. Mechanically, OsBZR1 directly promotes CSA
      expression and CSA directly triggers expression of sugar partitioning and
      metabolic genes during pollen and seed development. These findings provide
      insight into how BRs enhance plant reproduction and grain yield in an important
      agricultural crop. 

PMID- 25754972
TI  - The profile of the epidermal growth factor system in rat endometrium during
      postpartum involution period.
AB  - The epidermal growth factor (EGF) plays a crucial role in the control of uterine
      cell proliferation, growth and differentiation. This study was designed to
      investigate the spatiotemporal expression pattern and localization of the EGF
      receptor/ligand system during the process of uterine involution using
      immunohistochemistry. Our results indicated that the expression of the ErbB/HER
      receptors and their ligands varied with structural changes in the uterus at
      different days of involution. Supranuclear punctate ErbB1 immunostaining was
      observed in the luminal and glandular epithelial cells and endometrial
      fibroblasts. Moderate ErbB2/HER2 immunoreactivity was observed in the lateral
      membrane and cytoplasm of the epithelial cells on the 1st, 3rd and 5th days and
      was decreased on the other days of involution. The amount of nuclear and
      cytoplasmic ErbB3/HER3 and ErbB4/HER4 immunostaining remained constant throughout
      the postpartum period. The EGF immunoreaction was weak in the luminal and
      glandular epithelium throughout the involution period. Although the cytoplasmic
      AREG immunoreactivity in the glandular epithelium was stronger on the 1st and 3rd
      days compared with the other days of involution, NRG1 immunostaining was weak on
      the 1st and 3rd days and was moderate in the apical cytoplasm on the 10th and
      15th days of involution. The macrophages displayed strong cytoplasmic
      immunoreactivity for ErbB3/HER3, ErbB4/HER4, EGF, AREG and NRG. Strong, moderate
      and weak immunostaining for ErbB2/HER2, ErbB4/HER4 and other proteins (ErbB1,
      ErbB3, AREG and NRG), respectively, was present in the myometrial smooth muscle
      cells. These findings support the hypothesis that the EGFsystem plays a role in
      the development of various physiological changes associated with uterine
      involution. 

PMID- 25754974
TI  - Spontaneous non-verbal counting in toddlers.
AB  - A wealth of studies have investigated numerical abilities in infants and in
      children aged 3 or above, but research on pre-counting toddlers is sparse. Here
      we devised a novel version of an imitation task that was previously used to
      assess spontaneous focusing on numerosity (i.e. the predisposition to grasp
      numerical properties of the environment) to assess whether pre-counters would
      spontaneously deploy sequential (item-by-item) enumeration and whether this
      ability would rely on the object tracking system (OTS) or on the approximate
      number system (ANS). Two-and-a-half-year-olds watched the experimenter performing
      one-by-one insertion of 'food tokens' into an opaque animal puppet and then were
      asked to imitate the puppet-feeding behavior. The number of tokens varied between
      1 and 6 and each numerosity was presented many times to obtain a distribution of
      responses during imitation. Many children demonstrated attention to the
      numerosity of the food tokens despite the lack of any explicit cueing to the
      number dimension. Most notably, the response distributions centered on the target
      numerosities and showed the classic variability signature that is attributed to
      the ANS. These results are consistent with previous studies on sequential
      enumeration in non-human primates and suggest that pre-counting children are
      capable of sequentially updating the numerosity of non-visible sets through
      additive operations and hold it in memory for reproducing the observed behavior. 

PMID- 25754975
TI  - HDlive imaging of circumvallate placenta.

PMID- 25754976
TI  - Educational influences on early retirement through disability in Ireland.
AB  - BACKGROUND: Studies suggest a higher prevalence of early retirement through
      disability among older people with lower educational attainment. There have been
      no national studies in Ireland on the factors that affect early withdrawal from
      the labour force through disability or long-term illness. AIMS: To identify and
      analyse potential impacts of education on early retirement through disability in
      the over 50 age cohort of the Irish Labour force. METHODS: We analysed the
      educational attainment of participants using The Irish Longitudinal Study of
      Ageing (TILDA). The group of interest were those aged 50-75 who had retired
      early. The sample was dichotomized on disability. Examination of interviewer
      recorded information on background influences determining early retirement
      decisions included the following factors: age, gender, education, family and
      socio-economic circumstances, including parental education. RESULTS: A total of
      334 of 1179 study subjects (28%) retired early through disability. Comparison of
      those retired early with and without disability showed a significantly higher
      frequency of lower educational attainment both personally and for parents. Men
      with lower educational attainment and from a non-professional background were
      more likely to retire early through disability. Non-professional disabled
      respondents with less well-educated parents had lower educational attainment than
      non-disabled respondents. CONCLUSIONS: Among TILDA participants, educational
      attainment appears to influence early retirement through disability. The sector
      of previous employment was also a significant factor. Behaviour, lifestyle and
      employment choice are influenced by educational level, which may affect cognitive
      ability to process health information. Factors affecting the education-disability
      relationship could include parental education, employment status and socio
      economic characteristics.

PMID- 25754977
TI  - Disability and disability benefit seeking in chronic low back pain.
AB  - BACKGROUND: Numerous studies suggest psychosocial factors contribute to
      functional disability in patients with chronic low back pain (CLBP). However,
      less is known about the association of psychosocial factors, such as depression,
      with seeking medical disability benefits and their prevalence in benefit seekers
      compared with patients already receiving such payments. AIMS: To determine if
      characteristics of disability benefit seekers differ from patients receiving
      disability benefits and if both differ from patients not dependent on such
      payments. METHODS: Questionnaire data on pain, health-related quality of life,
      depression, social support, substance abuse, adverse childhood experiences and
      disability seeking were obtained from CLBP respondents recruited at 10 primary
      care clinics throughout Texas. A multinomial logistic regression model was
      computed using variables significantly associated with disability status and pain
      severity in univariate models. RESULTS: There were 213 participants. In full
      models, compared with those not on disability benefits, only depression symptoms
      were significantly associated with seeking disability benefits (odds ratio [OR] =
      1.13; 95% confidence interval [CI] 1.01-1.26) and only duration of pain was
      significantly associated with being on such benefits (OR = 1.05; 95% CI 1.01
      1.09). CONCLUSIONS: Patient characteristics differ between disability benefit
      seekers and those established on disability benefit payments. Depression may be a
      modifiable correlate of disability benefit seeking that if treated may reduce the
      number of patients who eventually come to depend on disability benefits.
      Additional data collection involving other pain syndromes is warranted to
      determine if these results are unique to CLBP or apply to other painful
      conditions.

PMID- 25754979
TI  - Reply to Eisen and McBryde.

PMID- 25754978
TI  - CD4+ T-Cell-Dependent Reduction in Hepatitis C Virus-Specific Neutralizing
      Antibody Responses After Coinfection With Human Immunodeficiency Virus.
AB  - BACKGROUND: Human immunodeficiency virus (HIV) infection leads to lower rates of
      hepatitis C virus (HCV) clearance after acute infection, higher HCV viremia, and
      accelerated progression of HCV-related fibrosis. The mechanisms underlying this
      acceleration of HCV progression by HIV are poorly understood, but HIV-induced
      dysfunction in the anti-HCV humoral immune response may play a role. METHODS: To
      define the effect of HIV coinfection on the anti-HCV antibody response, we
      measured anti-HCV envelope binding antibody titers, neutralizing antibody (nAb)
      titers, and nAb breadth of serum from HCV-infected subjects isolated
      longitudinally before and after incident HIV infection. RESULTS: A significant
      reduction in HCV envelope-specific binding antibody and nAb titers was detected
      in subjects with CD4(+) T-cell counts <350/mm(3) after HIV infection, and
      subjects with CD4(+) T-cell counts <200/mm(3) also showed a reduction in nAb
      breadth. Subjects who maintained CD4(+) T-cell counts >=350/mm(3) displayed
      little to no decline in antibody levels. CONCLUSIONS: Depletion of CD4(+) T cells
      by HIV infection results in a global decline in the anti-HCV envelope antibody
      response, including binding antibody titers, nAb titers, and nAb breadth.

PMID- 25754981
TI  - An Association Between Aspirin Use in Human Cases of Infective Endocarditis and
      Reduced Systemic Embolism Is Shown in Meta-analysis of Observational Studies.

PMID- 25754980
TI  - Structural Bone Deficits in HIV/HCV-Coinfected, HCV-Monoinfected, and HIV
      Monoinfected Women.
AB  - BACKGROUND: Coinfection with human immunodeficiency virus (HIV) and hepatitis C
      virus (HCV) is associated with reduced bone mineral density (BMD) and increased
      fracture rates, particularly in women. The structural underpinnings for skeletal
      fragility in coinfected women have not been characterized. We used tibial
      peripheral quantitative computed tomography to evaluate skeletal parameters in
      women, by HIV/HCV status. METHODS: We conducted a cross-sectional study among 50
      HIV/HCV-coinfected, 51 HCV-monoinfected, and 50 HIV-monoinfected women. Tibial
      volumetric BMD and cortical dimensions were determined with peripheral
      quantitative computed tomography. Race-specific z scores for age were generated
      using 263 female reference participants without HIV infection or liver disease.
      RESULTS: Coinfected participants had lower mean z scores for trabecular
      volumetric BMD (-0.85), cortical volumetric BMD (-0.67), cortical area (-0.61),
      and cortical thickness (-0.77) than reference participants (all P < .001). The
      smaller cortical dimensions were due to greater mean z scores for endosteal
      circumference (+0.67; P < .001) and comparable z scores for periosteal
      circumference (+0.04; P = .87). Trabecular volumetric BMD was lower in coinfected
      than in HCV- or HIV-monoinfected participants. HCV-infected women with stage 3-4
      liver fibrosis had lower mean z scores for trabecular volumetric BMD, cortical
      thickness, and total hip BMD those with stage 0-2 fibrosis. CONCLUSIONS: Compared
      with healthy reference patients, HIV/HCV-coinfected women had decreased tibial
      trabecular volumetric BMD, diminished cortical dimensions, and significant
      endocortical bone loss.

PMID- 25754982
TI  - HIV-1 Superinfection Resembles Primary Infection.
AB  - The relevance of superinfection as a model to identify correlates of protection
      against human immunodeficiency virus (HIV) depends on whether the superinfecting
      transmission resembles primary infection, which has not been established. Here,
      we characterize the genetic bottleneck in superinfected individuals for the first
      time. In all 3 cases, superinfection produced a spike in viral load and could be
      traced to a single, C-C chemokine receptor 5-tropic founder virus with shorter,
      less glycosylated variable regions than matched chronic viruses. These features
      are consistent with primary HIV transmission and provide support for the use of
      superinfection as a model to address correlates of protection against HIV. 

PMID- 25754983
TI  - Collision cross section measurements for biomolecules within a high-resolution FT
      ICR cell: theory.
AB  - In this study, an energetic hard-sphere ion-neutral collision model was proposed
      to bridge-link ion collision cross section (CCS) with the image current collected
      from a high-resolution Fourier transform ion cyclotron resonance (FT-ICR) cell.
      By investigating the nonlinear effects induced by high-order electric fields and
      image charge forces, the energetic hard-sphere collision model was validated
      through experiments. Suitable application regions for the energetic hard-sphere
      collision model, as well as for the conventional Langevin and hard-sphere
      collision models, were also discussed. The energetic hard-sphere collision model
      was applied in the extraction of ion CCSs from high-resolution FT-ICR mass
      spectra. Discussions in the present study also apply to FT-Orbitraps and FT
      quadrupole ion traps. 

PMID- 25754984
TI  - Interleukin-17A-induced inflammation does not influence the development of nasal
      polyps in murine model.
AB  - BACKGROUND: Nasal polyposis associated with chronic rhinosinusitis (CRS) is a
      chronic inflammatory disease that is characterized by infiltration of many
      inflammatory cells. Meanwhile, interleukin (IL)-17A is a well-known
      proinflammatory cytokine that induces both eosinophilic and neutrophilic
      inflammation. We investigated the role of IL-17A in the development of nasal
      polyps in the CRS murine model. METHODS: Eosinophilic CRS with nasal polyps was
      induced by using ovalbumin (OVA) and Staphylococcus aureus enterotoxin B (SEB) in
      wild-type BALB/c and IL-17A knockout (KO) mice. Histopathologic changes of the
      sinonasal cavity were evaluated using hematoxylin and eosin, Periodic acid
      Schiff, Sirius red, Masson's trichrome, and immunohistochemistry. The levels of
      total and OVA-specific immunoglobulin Es (IgEs) in sera were measured using
      enzyme-linked immunosorbent assay. The expression levels of IL-4, IL-5, and
      interferon-gamma (IFN-gamma) in the nasal mucosa were assessed by quantitative
      real-time polymerase chain reaction. RESULTS: Under the IL-17A deficiency, total
      and OVA-specific IgEs in sera were reduced significantly. Infiltration of both
      eosinophils and neutrophils into the nasal mucosa, subepithelial fibrosis, and
      goblet cell count also decreased significantly in IL-17A KO mice treated with
      both OVA and SEB compared with those in the wild-type counterpart. However, there
      were no significant differences in the number of polypoid lesions among groups.
      Meanwhile, IL-4 increased and IFN-gamma decreased in the nasal mucosa in IL-17A
      KO mice treated with both OVA and SEB. CONCLUSION: This study suggests that even
      though IL-17A plays an important role in both nasal inflammation and remodeling,
      it does not influence the development of nasal polypoid lesions.

PMID- 25754985
TI  - Protein disulfide isomerase as a novel target for cyclopentenone prostaglandins:
      implications for hypoxic ischemic injury.
AB  - Cyclooxygenase-2 (COX-2) is an important contributor to ischemic brain injury.
      Identification of the downstream mediators of COX-2 toxicity may allow the
      development of targeted therapies. Of particular interest is the cyclopentenone
      family of prostaglandin metabolites. Cyclopentenone prostaglandins (CyPGs) are
      highly reactive molecules that form covalent bonds with cellular thiols. Protein
      disulfide isomerase (PDI) is an important molecule for the restoration of
      denatured proteins following ischemia. Because PDI has several thiols, including
      thiols within the active thioredoxin-like domain, we hypothesized that PDI is a
      target of CyPGs and that CyPG binding of PDI is detrimental. CyPG-PDI binding was
      detected in vitro via immunoprecipitation and MS. CyPG-PDI binding decreased PDI
      enzymatic activity in recombinant PDI treated with CyPG, and PDI
      immunoprecipitated from neuronal culture treated with CyPG or anoxia. Toxic
      effects of binding were demonstrated in experiments showing that: (a)
      pharmacologic inhibition of PDI increased cell death in anoxic neurons, (b) PDI
      overexpression protected neurons exposed to anoxia and SH-SY5Y cells exposed to
      CyPG, and (c) PDI overexpression in SH-SY5Y cells attenuated ubiquitination of
      proteins and decreased activation of pro-apoptotic caspases. In conclusion, CyPG
      production and subsequent binding of PDI is a novel and potentially important
      mechanism of ischemic brain injury. We show that CyPGs bind to PDI,
      cyclopentenones inhibit PDI activity, and CyPG-PDI binding is associated with
      increased neuronal susceptibility to anoxia. Additional studies are necessary to
      determine the relative role of CyPG-dependent inhibition of PDI activity in
      ischemia and other neurodegenerative disorders. 

PMID- 25754986
TI  - Treating empty nose syndrome as a somatic symptom disorder.
AB  - Empty nose syndrome (ENS) is a rare complication of inferior turbinate resection,
      characterized by a paradoxical nasal obstruction sensation despite decreased
      nasal resistance. Here we report the case of a 37-year-old patient with ENS and
      severe functional impairment, who was diagnosed with a somatic symptom disorder
      and treated accordingly. Cognitive behavior therapy targeting dysfunctional
      beliefs and avoidance behaviors together with a treatment by venlafaxine resulted
      in dramatic functional improvement between month 2 and month 4. At month 6, the
      patient was displaying back-to-normal levels of functioning and was no longer
      seeking care for ENS. Treating ENS as a somatic symptom disorder might constitute
      a first-line, safe alternative to surgical treatment. 

PMID- 25754987
TI  - Effect of garlic powder on acrylamide formation in a low-moisture model system
      and bread baking.
AB  - BACKGROUND: Acrylamide (AA) is of concern worldwide because of its neurotoxicity,
      genotoxicity and reproductive/developmental toxicity. Consequently, methods for
      minimizing AA formation during food processing are vital. RESULTS: In this study,
      the formation and elimination of AA in an asparagine/glucose low-moisture model
      system were investigated by response surface methodology. The effect of garlic
      powder on the kinetics of AA formation/elimination was also evaluated. The AA
      content reached a maximum level (674.0 nmol) with 1.2 mmol of glucose and 1.2
      mmol of asparagine after heating at 200  degrees C for 6 min. The AA content was
      greatly reduced with the addition of garlic powder. Compared to without garlic
      powder, an AA reduction rate of 43% was obtained with addition of garlic powder
      at a mass fraction of 0.05 g. Garlic powder inhibited AA formation during the
      generation-predominant kinetic stage and had no effect on the degradation
      predominant kinetic stage. The effect of garlic powder on AA formation in bread
      and bread quality was also investigated. Adding a garlic powder mass fraction of
      15 g to 500 g of dough significantly (P < 0.05) reduced the formation of AA
      (reduction rate of 46%) and had no obvious effect on the sensory qualities of the
      bread. CONCLUSION: This study provides a possible method for reducing the AA
      content in bread and other heat-treated starch-rich foods.

PMID- 25754988
TI  - Recent advances in the understanding of immune-mediated nephrotic syndrome:
      diagnostic and prognostic implications.
AB  - Glomerular diseases with severe defects in glomerular permeability give rise to
      heavy proteinuria and can present as nephrotic syndrome. There are many different
      causes of the nephrotic syndrome and a renal biopsy is nearly always needed to
      elucidate the underlying disease. During the last decade, substantial advances
      have occurred in the understanding of the pathophysiological mechanisms involved
      in immune-mediated glomerular diseases. Here, we review the diagnostic and
      prognostic implications of recent progress on the understanding of membranous
      nephropathy, minimal change disease, focal segmental glomerulosclerosis,
      amyloidosis, IgA nephropathy and membranoproliferative glomerulonephritis. 

PMID- 25754989
TI  - Improvement of overactive bladder symptoms after tension-free vaginal mesh
      operation in women with pelvic organ prolapse: Correlation with preoperative
      urodynamic findings.
AB  - OBJECTIVES: To further elucidate the mechanisms of overactive bladder coexisting
      with pelvic organ prolapse. METHODS: A total of 100 consecutive women with stage
      2 or greater pelvic organ prolapse associated with cystocele were enrolled in the
      present prospective study. They underwent urodynamic studies and then received
      tension-free vaginal mesh operation. Urodynamic studies were carried out before
      and after the correction of pelvic organ prolapse using a single gauze pack in
      the vagina in the sitting position. The overactive bladder symptom score and
      International Prostate Symptom Score were collected before and 3 months after
      surgery. RESULTS: In 53 of 100 cases, pelvic organ prolapse was accompanied with
      overactive bladder, and detrusor overactivity was observed in 28 out of 53 pelvic
      organ prolapse with overactive bladder cases (52.8%). Detrusor overactivity was
      resolved in 18 and reduced in four out of 28 cases after the correction of pelvic
      organ prolapse by the gauze packing method. Of 53 patients who had overactive
      bladder preoperatively, overactive bladder symptoms disappeared in 35 cases
      (66.0%) and improved in six additional cases (11.3%) after tension-free vaginal
      mesh operation. A total of 20 of 25 cases whose overactive bladder symptoms
      disappeared or improved after surgery coincided with those who had shown either
      disappearance (n = 16) or improvement (n = 4) of detrusor overactivity after
      intravaginal gauze pack insertion in preoperative urodynamic studies. All scores
      in the overactive bladder symptom score decreased significantly after tension
      free vaginal mesh, as well as the International Prostate Symptom Score, except
      for night-time frequency. CONCLUSIONS: Pelvic organ prolapse-associated
      overactive bladder or detrusor overactivity conditions can be reversed in most
      cases within a short period of time after surgical correction of pelvic organ
      prolapse.

PMID- 25754990
TI  - Inhibition of PKC-Induced COX-2 and IL-8 Expression in Human Breast Cancer Cells
      by Glucosamine.
AB  - Breast cancer is a common cancer leading to many deaths among females.
      Cyclooxygenase-2 (COX-2) and interleukin-8 (IL-8) are two highly expressed
      inflammatory mediators to be induced by the protein kinase C (PKC) signaling via
      various inflammatory stimuli and both contribute significantly to cancer
      metastasis/progression. Glucosamine has been shown to act as an anti-inflammation
      molecule. The aim of this study was to clarify the role and acting mechanism of
      glucosamine during the PKC-regulation of COX-2/IL-8 expression and the associated
      impact on breast cancer. In MCF-7 breast cancer cells, glucosamine effectively
      suppresses the PKC induction of COX-2 and IL-8 promoter activity, mRNA and
      protein levels, as well as the production of prostaglandin E(2) (PGE(2)) and IL
      8. Glucosamine is able to promote COX-2 protein degradation in a calpain
      dependent manner and IL-8 protein degradation in calpain-dependent and proteasome
      dependent manners. The MAPK and NF-kappaB pathways are involved in PKC-induced
      COX-2 expression, but only the NF-kappaB pathway is involved in PKC-induced IL-8
      expression. Glucosamine attenuates PKC-mediated IkappaBalpha phosphorylation,
      nuclear NF-kappaB translocation, and NF-kappaB reporter activation. Both PGE(2)
      and IL-8 promote cell proliferation and IL-8 induces cell migration; thus,
      glucosamine appears to suppress PKC-induced cell proliferation and migration.
      Furthermore, glucosamine significantly inhibits the growth of breast cancer
      xenografts and this is accompanied by a reduction in COX-2 and IL-8 expression.
      In conclusion, glucosamine seems to attenuate the inflammatory response in vitro
      and in vivo and this occurs, at least in part by targeting to the NF-kappaB
      signaling pathway, resulting in an inhibition of breast cancer cell growth.

PMID- 25754991
TI  - Investigating Protein Structure and Evolution with SCOP2.
AB  - SCOP2 is a successor to the Structural Classification of Proteins (SCOP) database
      that organizes proteins of known structure according to their structural and
      evolutionary relationships. It was designed to provide a more advanced framework
      for the classification of proteins. The SCOP2 classification is described in
      terms of a directed acyclic graph in which each node defines a relationship of
      particular type that is represented by a region of protein structure and
      sequence. The SCOP2 data are accessible via SCOP2-Browser and SCOP2-Graph. This
      protocol unit describes different ways to explore and investigate the SCOP2
      evolutionary and structural groupings.

PMID- 25754992
TI  - Using REDItools to Detect RNA Editing Events in NGS Datasets.
AB  - RNA editing is a post-transcriptional/co-transcriptional molecular phenomenon
      whereby a genetic message is modified from the corresponding DNA template by
      means of substitutions, insertions, and/or deletions. It occurs in a variety of
      organisms and different cellular locations through evolutionally and
      biochemically unrelated proteins. RNA editing has a plethora of biological
      effects including the modulation of alternative splicing and fine-tuning of gene
      expression. RNA editing events by base substitutions can be detected on a genomic
      scale by NGS technologies through the REDItools package, an ad hoc suite of
      Python scripts to study RNA editing using RNA-Seq and DNA-Seq data or RNA-Seq
      data alone. REDItools implement effective filters to minimize biases due to
      sequencing errors, mapping errors, and SNPs. The package is freely available at
      Google Code repository (http://code.google.com/p/reditools/) and released under
      the MIT license. In the present unit we show three basic protocols corresponding
      to three main REDItools scripts.

PMID- 25754994
TI  - Expression data analysis with Reactome.
AB  - The Reactome database of curated biological pathways provides a tool for
      visualizing user-supplied expression data as an overlay on pathway diagrams,
      thereby affording an effective means to examine expression of the constituents of
      the pathway and determine whether all that are necessary are present. Several
      experiments can be visualized in succession, to determine whether expression
      changes with experimental conditions, a useful feature for examining a time
      course, dose-response, or disease progression.

PMID- 25754993
TI  - Scoring Large-Scale Affinity Purification Mass Spectrometry Datasets with MiST.
AB  - High-throughput Affinity Purification Mass Spectrometry (AP-MS) experiments can
      identify a large number of protein interactions, but only a fraction of these
      interactions are biologically relevant. Here, we describe a comprehensive
      computational strategy to process raw AP-MS data, perform quality controls, and
      prioritize biologically relevant bait-prey pairs in a set of replicated AP-MS
      experiments with Mass spectrometry interaction STatistics (MiST). The MiST score
      is a linear combination of prey quantity (abundance), abundance invariability
      across repeated experiments (reproducibility), and prey uniqueness relative to
      other baits (specificity). We describe how to run the full MiST analysis pipeline
      in an R environment and discuss a number of configurable options that allow the
      lay user to convert any large-scale AP-MS data into an interpretable,
      biologically relevant protein-protein interaction network.

PMID- 25754995
TI  - Using pLink to Analyze Cross-Linked Peptides.
AB  - pLink is a search engine for high-throughput identification of cross-linked
      peptides from their tandem mass spectra, which is the data-analysis step in
      chemical cross-linking of proteins coupled with mass spectrometry analysis. pLink
      has accumulated more than 200 registered users from all over the world since its
      first release in 2012. After 2 years of continual development, a new version of
      pLink has been released, which is at least 40 times faster, more versatile, and
      more user-friendly. Also, the function of the new pLink has been expanded to
      identifying endogenous protein cross-linking sites such as disulfide bonds and
      SUMO (Small Ubiquitin-like MOdifier) modification sites. Integrated into the new
      version are two accessory tools: pLabel, to annotate spectra of cross-linked
      peptides for visual inspection and publication, and pConfig, to assist users in
      setting up search parameters. Here, we provide detailed guidance on running a
      database search for identification of protein cross-links using the 2014 version
      of pLink.

PMID- 25754996
TI  - Effects of tung oilseed FAD2 and DGAT2 genes on unsaturated fatty acid
      accumulation in Rhodotorula glutinis and Arabidopsis thaliana.
AB  - Genetic engineering to produce valuable lipids containing unsaturated fatty acids
      (UFAs) holds great promise for food and industrial applications. Efforts to
      genetically modify plants to produce desirable UFAs with single enzymes, however,
      have had modest success. The key enzymes fatty acid desaturase (FAD) and
      diacylglycerol acyltransferase (DGAT) are responsible for UFA biosynthesis (a
      push process) and assembling fatty acids into lipids (a pull process) in plants,
      respectively. To examine their roles in UFA accumulation, VfFAD2 and VfDGAT2
      genes cloned from Vernicia fordii (tung tree) oilseeds were conjugated and
      transformed into Rhodotorula glutinis and Arabidopsis thaliana via Agrobacterium
      tumefaciens. Real-time quantitative PCR revealed variable gene expression levels
      in the transformants, with a much higher level of VfDGAT2 than VfFAD2. The
      relationship between VfFAD2 expression and linoleic acid (C18:2) increases in R.
      glutinis (R (2) = 0.98) and A. thaliana (R (2) = 0.857) transformants was
      statistically linear. The VfDGAT2 expression level was statistically correlated
      with increased total fatty acid content in R. glutinis (R (2) = 0.962) and A.
      thaliana (R (2) = 0.8157) transformants. With a similar expression level between
      single- and two-gene transformants, VfFAD2-VfDGAT2 co-transformants showed a
      higher linolenic acid (C18:3) yield in R. glutinis (174.36 % increase) and A.
      thaliana (14.61 % increase), and eicosatrienoic acid (C20:3) was enriched (17.10
      % increase) in A. thaliana. Our data suggest that VfFAD2-VfDGAT2 had a
      synergistic effect on UFA metabolism in R. glutinis, and to a lesser extent, A.
      thaliana. These results show promise for further genetic engineering of plant
      lipids to produce desirable UFAs.

PMID- 25754997
TI  - miRNAome analysis associated with anatomic and transcriptomic investigations
      reveal the polar exhibition of corky split vein in boron deficient Citrus
      sinensis.
AB  - Corky split vein can develop under long-term boron deficient conditions in Citrus
      sinensis L. Osbeck cv. Newhall. This symptom only occurs in the upper rather than
      the lower epidermis of old leaves. Our previous study demonstrated that vascular
      hypertrophy was involved in the symptoms, and the 3rd developmental stage of
      corky split vein (BD3) was the critical stage for phenotype formation. Here, we
      performed an intensive study on the BD3 vein and its control sample (CK3 vein). A
      lignin test demonstrated that the lignin content in BD3 vein was approximately
      1.7 times more than the CK3 vein. Anatomical investigation of the corky split
      vein indicated that the upper epidermis was destroyed by overgrowing vascular
      cells, and the increased lignin may contribute to vascular cell differentiation
      and wounding-induced lignification. In a subsequent small RNA sequencing of the
      BD3 and CK3 veins, 99 known miRNAs and 22 novel miRNAs were identified.
      Comparative profiling of these miRNAs demonstrated that the 57 known miRNAs and
      all novel miRNAs exhibited significant expression differences between the two
      small RNAs libraries of the BD3 and CK3 veins. Associated with our corresponding
      digital gene expression data, we propose that the decreased expression of two
      miRNAs, csi-miR156b and csi-miR164, which leads to the up-regulation of their
      target genes, SPLs (csi-miR156b-targeted) and CUC2 (csi-miR164-targeted), may
      promote vascular cell division and orderless stage transition in old leaves. 

PMID- 25754998
TI  - Bactericidal mode of action of bedaquiline.
AB  - OBJECTIVES: It is not fully understood why inhibiting ATP synthesis in
      Mycobacterium species leads to death in non-replicating cells. We investigated
      the bactericidal mode of action of the anti-tubercular F1Fo-ATP synthase
      inhibitor bedaquiline (SirturoTM) in order to further understand the lethality of
      ATP synthase inhibition. METHODS: Mycobacterium smegmatis strains were used for
      all the experiments. Growth and survival during a bedaquiline challenge were
      performed in multiple media types. A time-course microarray was performed during
      initial bedaquiline challenge in minimal medium. Oxygen consumption and proton
      motive force measurements were performed on whole cells and inverted membrane
      vesicles, respectively. RESULTS: A killing of 3 log10 cfu/mL was achieved 4-fold
      more quickly in minimal medium (a glycerol carbon source) versus rich medium (LB
      with Tween 80) during bedaquiline challenge. Assessing the accelerated killing
      condition, we identified a transcriptional remodelling of metabolism that was
      consistent with respiratory dysfunction but inconsistent with ATP depletion. In
      glycerol-energized cell suspensions, bedaquiline caused an immediate 2.3-fold
      increase in oxygen consumption. Bedaquiline collapsed the transmembrane pH
      gradient, but not the membrane potential, in a dose-dependent manner. Both these
      effects were dependent on binding to the F1Fo-ATP synthase. CONCLUSIONS:
      Challenge with bedaquiline results in an electroneutral uncoupling of respiration
      driven ATP synthesis. This may be a determinant of the bactericidal effects of
      bedaquiline, while ATP depletion may be a determinant of its delayed onset of
      killing. We propose that bedaquiline binds to and perturbs the a-c subunit
      interface of the Fo, leading to futile proton cycling, which is known to be
      lethal to mycobacteria.

PMID- 25754999
TI  - Vancomycin-resistant Enterococcus faecium harbouring vanN in Canada: a case and
      complete sequence of pEfm12493 harbouring the vanN operon.

PMID- 25755000
TI  - Prevalence and risk factors for carriage of antimicrobial-resistant Escherichia
      coli on household and small-scale chicken farms in the Mekong Delta of Vietnam.
AB  - OBJECTIVES: To describe the prevalence of antimicrobial resistance among
      commensal Escherichia coli isolates on household and small-scale chicken farms,
      common in southern Vietnam, and to investigate the association of antimicrobial
      resistance with farming practices and antimicrobial usage. METHODS: We collected
      data on farming and antimicrobial usage from 208 chicken farms. E. coli was
      isolated from boot swab samples using MacConkey agar (MA) and MA with
      ceftazidime, nalidixic acid or gentamicin. Isolates were tested for their
      susceptibility to 11 antimicrobials and for ESBL production. Risk factor analyses
      were carried out, using logistic regression, at both the bacterial population and
      farm levels. RESULTS: E. coli resistant to gentamicin, ciprofloxacin and third
      generation cephalosporins was detected on 201 (96.6%), 191 (91.8%) and 77 (37.0%)
      of the farms, respectively. Of the 895 E. coli isolates, resistance to
      gentamicin, ciprofloxacin and third-generation cephalosporins was detected in 178
      (19.9%), 291 (32.5%) and 29 (3.2%) of the isolates, respectively. Ciprofloxacin
      resistance was significantly associated with quinolone usage (OR = 2.26) and
      tetracycline usage (OR = 1.70). ESBL-producing E. coli were associated with farms
      containing fish ponds (OR = 4.82). CONCLUSIONS: Household and small farms showed
      frequent antimicrobial usage associated with a high prevalence of resistance to
      the most commonly used antimicrobials. Given the weak biocontainment, the high
      prevalence of resistant E. coli could represent a risk to the environment and to
      humans.

PMID- 25755001
TI  - Highly frequent HIV-1 minority resistant variants at baseline of the ANRS 139
      TRIO trial had a limited impact on virological response.
AB  - OBJECTIVES: To assess the prevalence of minority resistant variants (MRVs) at
      baseline and their impact on the virological response. The ANRS 139 TRIO trial
      evaluated the combination of raltegravir, etravirine and darunavir, plus an
      optimized background therapy, in 87% of cases. Patients were highly experienced
      and harboured multiresistant viruses, but were naive to the three drugs, and
      showed a high level of virological suppression. METHODS: Ultra-deep sequencing of
      reverse transcriptase, protease and integrase regions was performed at the trial
      baseline, and sequences were interpreted according to the ANRS algorithm. MRVs
      were assessed using MiSeq and 454 technologies (limit of detection 1%). RESULTS:
      At baseline, minority variants with at least one NRTI, one NNRTI, one PI, one
      major PI or an integrase inhibitor resistance-associated mutation were present in
      46%, 45%, 68%, 24% and 13% of patients, respectively. When minority variants are
      taken into account, the prevalence of resistance to etravirine, darunavir and
      raltegravir at baseline was 29%, 40% and 9%, respectively. No difference was
      observed in the prevalence of MRVs between patients with virological failure and
      those with virological success, except a trend for patients exhibiting baseline
      etravirine MRVs (50% versus 26%, P = 0.09). CONCLUSIONS: We have shown a high
      level of MRVs at baseline in highly pre-treated patients harbouring
      multiresistant viruses. However, these MRVs were not associated with an increased
      risk of virological failure, except for a trend for etravirine MRVs.

PMID- 25755003
TI  - Thar drought: A complete public health failure.

PMID- 25755002
TI  - Incidence of antibiotics resistance among uropathogens in Omani children
      presenting with a single episode of urinary tract infection.
AB  - Urinary tract infection (UTI) is one of the most common community-acquired
      infections. Different organisms can be the cause of UTI in children, with
      resistance to antibiotics becoming a significant problem in the choice of
      treatment. Worldwide studies have documented the prevalence of uropathogens in
      different countries. However, there is no previous study documenting the
      incidence of different uropathogens in Oman. We aim to report the most common
      uropathogens and their antibiotic sensitivity patterns in children presenting
      with documented, single episode UTI at a tertiary hospital in Oman. A
      retrospective analysis of all Omani children below 14 years who presented with a
      case of first documented UTI to SQUH between September 2008 and August 2012 was
      conducted. Data were obtained from the patients' electronic records in the
      hospital information system. Data were then analyzed using SSPS (Statistical
      Package for Social Sciences program, Version 20, IBM, Chicago, IL, USA). In the
      retrospective review of all urine cultures, 438 positive urine cultures were
      identified. Out of those, 208 (47.5%) belonged to children with their first
      episode of UTI. Thirty-three patients were excluded and 75 patients were included
      in the final analysis. Escherichia coli was the most frequently encountered
      uropathogen in our cohort (69%), followed by Klebsiella pneumoniae infection
      (17%). Nearly half (46.6%) of these two common organism were resistant to
      Cotrimoxazole, while 31% of them were resistant to Augmentin. Twenty-four percent
      of the E. coli and K. pneumoniae strains were resistant to Cefuroxime, and only
      10% were resistant to nitrofurantoin. Both Augmentin and Cotrimoxazole should not
      be the first line antibiotics to treat UTI. 

PMID- 25755004
TI  - Editorial overview: elucidation of protein translocation pathways, part II.

PMID- 25755005
TI  - "Roar" of blaNDM-1 and "silence" of blaOXA-58 co-exist in Acinetobacter pittii.
AB  - Acinetobacter pittii 44551 was recovered from a patient with gout combined with
      tuberculosis and was found to harbor the carbapenemase genes blaNDM-1 and blaOXA
      58 on two different plasmids pNDM-44551 and pOXA58-44551, respectively. pNDM
      44551 displayed high self-transferability across multiple bacterial species,
      while pOXA58-44551 was likely co-transferable with pNDM-44551 into A. baumannii
      receipts. pNDM-44551 was a close variant of the previously characterized pNDM
      BJ01, and the blaNDM-1 gene cluster was arranged sequentially as orfA, ISAba14,
      aphA6, ISAba125, blaNDM-1, bleMBL, DeltatrpF, dsbC, tnpR, and zeta. pOXA58-44551
      was a repAci9-containing plasmid, and blaOXA-58 was embedded in a 372F-ISAba3
      like-blaOXA-58-ISAba3 structure. The mobile genetic platforms of blaNDM-1 and
      blaOXA-58 herein showed some differences from their previously characterized
      variants. The production of NDM-1 in strain 44551 contributed the majority to its
      high resistance to carbapenems, while the blaOXA-58 stayed silent most likely due
      to the lack of an upstream promoter to drive its transcription. Increased
      surveillance of Acinetobacter co-harboring blaNDM-1 (active) and blaOXA-58
      (either active or silent) is urgently needed. 

PMID- 25755006
TI  - Artemisinin Represses Telomerase Subunits and Induces Apoptosis in HPV-39
      Infected Human Cervical Cancer Cells.
AB  - Artemisinin, a plant-derived antimalarial drug with relatively low toxicity on
      normal cells in humans, has selective anticancer activities in various types of
      cancers, both in vitro and in vivo. In the present study, we have investigated
      the anticancer effects of artemisinin in human cervical cancer cells, with
      special emphasis on its role in inducing apoptosis and repressing cell
      proliferation by inhibiting the telomerase subunits, ERalpha which is essential
      for maintenance of the cervix, and downstream components like VEGF, which is
      known to activate angiogenesis. Effects of artemisinin on apoptosis of ME-180
      cells were measured by flow cytometry, DAPI, and annexin V staining. Expression
      of genes and proteins related to cell proliferation and apoptosis was quantified
      both at the transcriptional and translational levels by semi-quantitative RT-PCR
      and western blot analysis, respectively. Our findings demonstrated that
      artemisinin significantly downregulated the expression of ERalpha and its
      downstream component, VEGF. Antiproliferative activity was also supported by
      decreased telomerase activity and reduced expression of hTR and hTERT subunits.
      Additionally, artemisinin reduced the expression of the HPV-39 viral E6 and E7
      components. Artemisinin-induced apoptosis was confirmed by FACS, nuclear
      chromatin condensation, annexin V staining. Increased expression of p53 with
      concomitant decrease in expression of the p53 inhibitor Mdm2 further supported
      that artemisinin-induced apoptosis was p53-dependent. The results clearly
      indicate that artemisinin induces antiproliferative and proapoptotic effects in
      HPV-39-infected ME-180 cells, and warrants further trial as an effective
      anticancer drug.

PMID- 25755007
TI  - Experimental evidence of chemical components in the bonding of helium and neon
      with neutral molecules.
AB  - The complexes of helium and neon with gaseous neutral molecules are generally
      perceived to be van der Waals adducts held together by physical (non-covalent)
      forces, owing to the combination of size (exchange) repulsion with
      dispersion/induction attraction. Molecular beam experiments confirm that this is
      the case for He-CF4 , Ne-CF4 adducts, but revealed that the interaction of He and
      Ne with CCl4 features an appreciable contribution of chemical components that
      arise from the anisotropy of the electron density of CCl4 that enhances a charge
      transfer from Ng (Ng=He, Ne). These findings furnish a novel assay of the bonding
      capabilities of helium and neon, and invite to revisit the neutral complexes of
      these elements as systems of chemical relevance. The CCl4 -Ng are also peculiar
      examples of halogen bonds, a group of interactions of major current concern.
      Finally, this investigation is a prelude to the development of semi-empirical
      models for force fields aimed to the unified description of static and dynamical
      properties of systems of comparable or higher complexity. 

PMID- 25755008
TI  - In situ generation of Ni nanoparticles from metal-organic framework precursors
      and their use for biomass hydrodeoxygenation.
AB  - So far, in situ-generated Ni nanoparticles have been reported to be efficient
      catalysts for tar cracking during wood liquefaction by pyrolysis. Herein, their
      performance in further bio-oil conversion steps is evaluated. Nanoparticles were
      generated for the first time from a Ni-containing metal-organic framework, MIL
      77, during the hydrotreatment of glycerol-solvolyzed lignocellulosic (LC)
      biomass. Reactions were conducted at 300  degrees C and the H2 pressure was 8 MPa
      in a slurry reactor. The catalytic activity and selectivity of the deoxygenation
      and hydrocracking reactions for real biomass-derived feedstock using in situ
      generated nanoparticles was compared with Ni nanoparticles dispersed on a silica
      alumina support (commercial Ni/SiO2 -Al2 O3 catalyst). The mass activity of the
      in situ-generated nanoparticles for hydrogenolysis was more than ten times higher
      in comparison to their commercial analogues, and their potential for the use in
      LC biorefinery is discussed. 

PMID- 25755009
TI  - Effect of Repeated Injections of Adenosine Diphosphate-Encapsulated Liposomes
      Coated with a Fibrinogen gamma-Chain Dodecapeptide Developed as a Synthetic
      Platelet Substitute on Accelerated Blood Clearance in a Healthy and an Anticancer
      Drug-Induced Thrombocytopenia Rat Model.
AB  - Adenosine diphosphate (ADP)-encapsulated liposomes coated with a fibrinogen gamma
      chain dodecapeptide [H12 (dodecapeptide ((400) HHLGGAKQAGDV(411) ))-(ADP)
      liposome] is a synthetic platelet substitute, in which the surface is covered
      with polyethylene glycol (PEG). It has been reported that repeated injections of
      PEGylated liposomes induce an accelerated blood clearance (ABC) phenomenon, which
      involves a loss in the long-circulation half-life of the material when
      administered repeatedly to the same animals. The objective of this study was to
      determine whether the ABC phenomenon was induced by repeated injections of H12
      (ADP)-liposome in healthy and anticancer drug-induced thrombocytopenia model
      rats. The findings show that the ABC phenomenon was induced by healthy rats that
      were repeatedly injected with H12-(ADP)-liposomes at the interval of 5 days at a
      dose of 10 mg lipids/kg. The ABC phenomenon involves the production of anti-H12
      (ADP)-liposome immunoglobulin M (IgM) and complement activation. On the other
      hand, when thrombocytopenia model rats were repeatedly injected with H12-(ADP)
      liposomes under the same conditions, no ABC phenomenon, nor was any suppression
      of anti-H12-(ADP)-liposome IgM-mediated complement activation observed. We thus
      conclude that the repeated injection of H12-(ADP)-liposome treatment in rat model
      with anticancer drug-induced thrombocytopenia did not induce the ABC phenomenon.

PMID- 25755010
TI  - On/off switching of bit readout in bias-enhanced tunnel magneto-Seebeck effect.
AB  - Thermoelectric effects in magnetic tunnel junctions are promising to serve as the
      basis for logic devices or memories in a "green" information technology. However,
      up to now the readout contrast achieved with Seebeck effects was magnitudes
      smaller compared to the well-established tunnel magnetoresistance effect. Here,
      we resolve this problem by demonstrating that the tunnel magneto-Seebeck effect
      (TMS) in CoFeB/MgO/CoFeB tunnel junctions can be switched on to a logic "1" state
      and off to "0" by simply changing the magnetic state of the CoFeB electrodes.
      This new functionality is achieved by combining a thermal gradient and an
      electric field. Our results show that the signal crosses zero and can be adjusted
      by tuning a bias voltage that is applied between the electrodes of the junction;
      hence, the name of the effect is bias-enhanced tunnel magneto-Seebeck effect
      (bTMS). Via the spin- and energy-dependent transmission of electrons in the
      junction, the bTMS effect can be configured using the bias voltage with much
      higher control than the tunnel magnetoresistance and even completely suppressed
      for only one magnetic configuration. Moreover, our measurements are a step
      towards the experimental realization of high TMS ratios without additional bias
      voltage, which are predicted for specific Co-Fe compositions. 

PMID- 25755011
TI  - A 7-month-old male with Allan-Herndon-Dudley syndrome and the power of T3.
AB  - Allan-Herndon-Dudley syndrome (AHDS, MIM 300523) is an X-linked neurodegenerative
      disorder characterized by intellectual disability, severe hypotonia, diminished
      muscle mass, and progressive spastic paraplegia. All affected males have
      pathognomonic thyroid profiles with an elevated T3 , low-normal free T4 , and
      normal TSH. Mutations in the monocarboxylate transporter 8 (MCT8) gene, SLC16A2,
      have been found to be causative. Here, we describe a proband whose extensive
      evaluation and ultimate diagnosis of AHDS unmasked three previously undiagnosed
      generations of affected individuals in one family. This case illustrates the need
      for clinicians to consider obtaining full thyroid studies on individuals with the
      non-specific findings of severe hypotonia, failure to thrive, and gross motor
      delay.

PMID- 25755012
TI  - Mechanochromic luminescence of copper iodide clusters.
AB  - Luminescent mechanochromic materials are particularly appealing for the
      development of stimuli-responsive materials. Establishing the mechanism
      responsible for the mechanochromism is always an issue owing to the difficulty in
      characterizing the ground phase. Herein, the study of real crystalline polymorphs
      of a mechanochromic and thermochromic luminescent copper iodide cluster permits
      us to clearly establish the mechanism involved. The local disruption of the
      crystal packing induces changes in the cluster geometry and in particular the
      modification of the cuprophilic interactions, which consequently modify the
      emissive states. This study constitutes a step further toward the understanding
      of the mechanism involved in the mechanochromic luminescent properties of
      multimetallic coordination complexes. 

PMID- 25755013
TI  - Association of UCP-3 rs1626521 with obesity and stomach functions in humans.
AB  - OBJECTIVE: To examine the association of gene variants of uncoupling proteins
      (UCP)-2 and -3 with obesity and gastrointestinal (GI) traits. METHODS: In 255
      overweight or obese adults, the associations of gene variants in UCP-2 (-3474,
      rs659366) and UCP-3 (rs1626521, rs2075577, rs15763) with body weight (BW) and GI
      traits were studied. Gene variants were genotyped by TaqMan(r) assay. The
      associations of genotypes with BW and GI traits (gastric emptying, gastric
      volume, satiety by buffet meal, satiation by nutrient drink test and GI hormones)
      were assessed using ANOVA corrected for false detection rate (FDR). RESULTS: A
      novel UCP-3 gene variant, rs1626521, was identified; it was associated with BW (P
      = 0.039), waist circumference (P = 0.035), and significantly higher postprandial
      gastric volume (P = 0.003) and calories ingested at buffet meal (P = 0.006, both
      significant with FDR). In a subgroup of 11 participants, rs1626521 was also
      associated with reduced mitochondrial bioenergetics efficiency in skeletal muscle
      (P = 0.051). In an in vitro study in HEK293 cells, rs1626521 reduced UCP-3
      protein expression (P = 0.049). Associations detected between other genotypes and
      GI traits were nonsignificant with FDR. CONCLUSIONS: A newly identified
      functional variant (rs1626521) in UCP-3 affects postprandial gastric functions
      and satiety and may contribute to weight gain and alter human mitochondrial
      function.

PMID- 25755015
TI  - Efficient biosorption of lead(II) and cadmium(II) ions from aqueous solutions by
      functionalized cell with intracellular CaCO3 mineral scaffolds.
AB  - The functionalized Saccharomyces cerevisiae cell with biogenic intracellular
      CaCO3 mineral scaffold, synthesized via a simple and environmentally friendly
      approach, was efficient for removing lead (II) and cadmium (II) ions from aqueous
      solutions. The CaCO3 mineral scaffold could promote the uptake of the heavy metal
      ions and increase the biosorption capabilities of the adsorbent. Compared with
      the Freundlich isotherm, Langmuir model more fitted the equilibrium data. The
      maximum removal capacity of functionalized cells for Pb(II) and Cd(II) was 116.69
      and 42.63mgg(-1), respectively. Further investigation showed that the adsorbent
      had high removal efficiency for trace amount of heavy metal ions. Adsorption data
      were modeled using the pseudo-first-order, pseudo-second-order and intra-particle
      diffusion kinetics equations. The results indicated that pseudo-second-order
      kinetic equation and intra-particle diffusion model could better describe the
      adsorption kinetics. The heavy metal ions might be removed by functionalized
      cells via membrane transport of metal ions and precipitation transformation. 

PMID- 25755014
TI  - Effects of four types of dilute acid washing on moso bamboo pyrolysis using Py
      GC/MS.
AB  - The influences of four types of dilute acid washing (H2SO4, HCl, HF, HNO3) on
      moso bamboo pyrolysis were investigated via pyrolysis-gas chromatography/mass
      spectrometry (Py-GC/MS). The effects of acid washings on the inorganics contents
      and the chemical structure were also analyzed. The results indicated that all the
      acid washings could effectively remove a large portion of inorganics and disrupt
      the chemical structure to a certain extent. HCl-washing behaved the best in
      removing inorganics and had the most marked disruption effect on bamboo
      structure. Acid washings promoted the bamboo pyrolysis and increased the contents
      of both phenols and sugars. HCl-washing had the most significant promotion effect
      on the levoglucosan formation with the absolute peak area increasing from
      8.12*10(8) to 1.92*10(9). The absolute peak areas of 2,3-dihydrobenzofuran
      decreased more or less after acid washings. All the acid washings except H2SO4
      washing could significantly increase the absolute peak area of methoxyeugenol. 

PMID- 25755016
TI  - Bioaugmentation with an anaerobic fungus in a two-stage process for biohydrogen
      and biogas production using corn silage and cattail.
AB  - Bioaugmentation with an anaerobic fungus, Piromyces rhizinflata YM600, was
      evaluated in an anaerobic two-stage system digesting corn silage and cattail.
      Comparable methane yields of 328.8+/-16.8mLg(-1)VS and 295.4+/-14.5mLg(-1)VS and
      hydrogen yields of 59.4+/-4.1mLg(-1)VS and 55.6+/-6.7mLg(-1)VS were obtained for
      unaugmented and bioaugmented corn silage, respectively. Similar CH4 yields of
      101.0+/-4.8mLg(-1)VS and 104+/-19.1mLg(-1)VS and a low H2 yield (<1mLg(-1)VS)
      were obtained for unaugmented and bioaugmented cattail, respectively. However,
      bioaugmentation resulted in an initial increase in CH4 and H2 production rates
      and also increased volatile fatty acid degradation rate for both substrates. Our
      study demonstrates the potential of bioaugmentation with anaerobic fungus for
      improving the digestibility of lignocellulose substrates for biogas and
      biohydrogen production. 

PMID- 25755017
TI  - Comments on 'A cautionary note concerning the use of stabilized weights in
      marginal structural models' by D. Talbot, J. Atherton, A. M. Rossi, S. L. Bacon,
      and G. Lefebvre.

PMID- 25755018
TI  - DNA binding activity of Anabaena sensory rhodopsin transducer probed by
      fluorescence correlation spectroscopy.
AB  - Anabaena sensory rhodopsin transducer (ASRT) is believed to be a major player in
      the photo-signal transduction cascade, which is triggered by Anabaena sensory
      rhodopsin. Here, we characterized DNA binding activity of ASRT probed by using
      fluorescence correlation spectroscopy. We observed clear decrease of diffusion
      coefficient of DNA upon binding of ASRT. The dissociation constant, K(D), of ASRT
      to 20 bp-long DNA fragments lied in micro-molar range and varied moderately with
      DNA sequence. Our results suggest that ASRT may interact with several different
      regions of DNA with different binding affinity for global regulation of several
      genes that need to be activated depending on the light illumination.

PMID- 25755019
TI  - Postural sway in single-limb and bilateral quiet standing after unilateral total
      knee arthroplasty.
AB  - AIM: To investigate whether total knee arthroplasty (TKA) was associated with
      stability in single-limb stance and whether reduced stability in single-limb
      stance was associated with increased postural sway in bilateral quiet standing.
      METHODS: 3D kinematics for center of mass was used to assess postural sway in 23
      subjects with TKA and 23 controls. Tests included bilateral quiet standing with
      and without vision and on a compliant surface, and single-limb stance. RESULTS:
      30% of the subjects in the TKA group were unable to maintain single-limb stance
      for 20s on any leg. Of the 70% in the TKA group able to stand on one leg, mean
      sway velocity in the medio-lateral direction was marginally higher for the
      prosthetic side (p=.02), but no differences were found between the TKA and the
      control group in single-limb stance. Performance in bilateral quiet standing was
      similar in TKA-subjects, able as well as unable to stand on one leg, and
      controls. Reduced quadriceps strength in the contralateral leg, higher BMI, and
      older age predicted failure to maintain single-limb stance. CONCLUSION: In
      subjects able to stand on one leg, performance was considered comparable between
      the prosthetic and contralateral side and between groups. Inability to stand on
      one leg did not affect postural sway in bilateral quiet standing. The results
      suggest that inability to maintain single-limb stance is explained by reduced
      physical capacity rather than the knee condition in itself. The present study
      emphasizes the importance of physical activity to improve strength and functional
      capacity.

PMID- 25755020
TI  - Supplemental food for Amblyseius swirskii in the control of thrips: feeding
      friend or foe?
AB  - BACKGROUND: In integrated pest management systems in greenhouse crops, the
      predatory mite Amblyseius swirskii is becoming increasingly important as a
      biological control agent of various pests, especially thrips and whiteflies. An
      emerging strategy to promote the predator's establishment and retention in the
      crop consists in providing food supplements. However, when faced with omnivorous
      pests, such as the western flower thrips, Frankliniella occidentalis, food
      supplements need to be applied with extreme care, in order not to boost
      population growth of the pest. This laboratory study was conducted to evaluate
      the impact of commercial products of Typha angustifolia pollen and decapsulated
      brine shrimp cysts (Artemia sp.) on populations of both pest and predator and on
      predator-prey interactions. RESULTS: Pollen was highly supportive for both F.
      occidentalis and A. swirskii, whereas Artemia cysts supported thrips populations
      to a lesser extent than those of the predator. Furthermore, a less pronounced
      reduction in thrips consumption by A. swirskii was observed in the presence of
      Artemia cysts as compared with T. angustifolia pollen. CONCLUSION: Artemia might
      be a valuable alternative to pollen for supporting populations of A. swirskii in
      order to improve thrips management, as they are less beneficial for the pest but
      do support population growth of A. swirskii.

PMID- 25755021
TI  - Signature-tagged mutagenesis of Vibrio vulnificus.
AB  - Vibrio vulnificus is the causative agent of primary septicemia, wound infection
      and gastroenteritis in immunocompromised people. In this study, signature-tagged
      mutagenesis (STM) was applied to identify the virulence genes of V. vulnificus.
      Using STM, 6,480 mutants in total were constructed and divided into 81 sets
      (INPUT pools); each mutant in a set was assigned a different tag. Each INPUT pool
      was intraperitoneally injected into iron-overloaded mice, and in vivo surviving
      mutants were collected from blood samples from the heart (OUTPUT pools). From the
      genomic DNA of mixed INPUT or OUTPUT pools, digoxigenin-labeled DNA probes
      against the tagged region were prepared and used for dot hybridization. Thirty
      tentatively attenuated mutants, which were hybridized clearly with INPUT probes
      but barely with OUTPUT probes, were negatively selected. Lethal doses of 11 of
      the 30 mutants were reduced to more than 1/100; of these, the lethal doses of 2
      were reduced to as low as 1/100,000. Transposon-inserted genes in the 11
      attenuated mutants were those for IMP dehydrogenase, UDP-N-acetylglucosamine-2
      epimerase, aspartokinase, phosphoribosylformylglycinamidine cyclo-ligase, malate
      Na (+) symporter and hypothetical protein. When mice were immunized with an
      attenuated mutant strain into which IMP dehydrogenase had been inserted with a
      transposon, they were protected against V. vulnificus infection. In this study,
      we demonstrated that the STM method can be used to search for the virulence genes
      of V. vulnificus. 

PMID- 25755022
TI  - Plasma fluctuation in estradiol-17beta and bone resorption markers around
      parturition in dairy cows.
AB  - Blood samples were obtained sequentially from 10 dairy cows around the time of
      parturition to assess plasma fluctuations in estradiol-17beta (E2) levels in
      association with those of several bone resorption markers. Plasma E2
      concentration increased sharply a few days prepartum and decreased quickly after
      parturition. In terms of bone resorption markers, the plasma level of tartrate
      resistant acid phosphatase isoform 5b (TRAP5b) rose significantly, commencing 1
      week prepartum, and was maintained at this level to a few days postpartum. The
      plasma concentration of carboxyterminal collagen cross-links of type-I collagen
      (CTx) increased significantly after parturition. These observations suggest that
      osteoclast-mediated bone resorption was activated after parturition when plasma
      E2 concentrations decreased. 

PMID- 25755023
TI  - Antibody induction directed against the tumor-associated MUC4 glycoprotein.
AB  - Mucin glycoproteins are important diagnostic and therapeutic targets for cancer
      treatment. Although several strategies have been developed to explore anti-tumor
      vaccines based on MUC1 glycopeptides, only few studies have focused on vaccines
      directed against the tumor-associated MUC4 glycoprotein. MUC4 is an important
      tumor marker overexpressed in lung cancer and uniquely expressed in pancreatic
      ductual adenocarcinoma. The aberrant glycosylation of MUC4 in tumor cells results
      in an exposure of its peptide backbone and the formation of tumor-associated
      glycopeptide antigens. Due to the low immunogenicity of these endogenous
      structures, their conjugation with immune stimulating peptide or protein carriers
      are required. In this study, MUC4 tandem-repeat glycopeptides were conjugated to
      the tetanus toxoid and used for vaccination of mice. Immunological evaluations
      showed that our MUC4-based vaccines induced very strong antigen-specific immune
      responses. In addition, antibody binding epitope analysis on glycopeptide
      microarrays, were demonstrating a clear glycosylation site dependence of the
      induced antibodies. 

PMID- 25755025
TI  - Self-esteem in children and adolescents with hearing loss.
AB  - Children with hearing loss are at risk for lower self-esteem due to differences
      from hearing peers relative to communication skills, physical appearance, and
      social maturity. This study examines the influence of generic factors unrelated
      to hearing loss (e.g., age, gender, temperament) and specific factors associated
      with hearing loss (e.g., age at identification, communication skills) on how
      children with hearing loss wearing cochlear implants or hearing aids appraise
      self-esteem. Fifty children with hearing loss wearing cochlear implants or
      hearing aids participated (Mean age: 12.88 years; mean duration of device use:
      3.43 years). Participants independently completed online questionnaires to assess
      communication skills, social engagement, self-esteem, and temperament. Children
      with hearing loss rated global self-esteem significantly more positively than
      hearing peers, t = 2.38, p = .02. Self-esteem ratings attained significant
      positive correlations with affiliation (r = .42, p = .002) and attention (r =
      .45, p = .001) temperaments and a significant negative association with
      depressive mood (r = - .60, p < .0001). No significant correlations emerged
      between self-esteem and demographic factors, communication skills, or social
      engagement. Because successful communication abilities do not always co-occur
      with excellent quality of life, clinicians and professionals working with
      children with hearing loss need to understand components contributing to self
      esteem to improve identification, counseling, and external referrals for children
      in this population.

PMID- 25755026
TI  - [Intracranial hypertension and jugular vein thrombosis].
AB  - BACKGROUND: Pseudotumor cerebri is an idiopathic increase in intracranial
      pressure, which commonly affects obese women of fertile age. The diagnostic
      criteria according to the guidelines of the German Society for Neurology are
      increased cerebrospinal fluid (CSF) pressure, symptoms of increased CSF pressure,
      normal results of CSF examination, no relevant medication and a lack of
      structural and vascular lesions in magnetic resonance imaging (MRI). CASE REPORT:
      This article presents the case of a 39-year-old male patient who presented at
      hospital with visual obscuration and recently occurred double vision. Except for
      a recently diagnosed thrombosis of the left jugular vein of unknown origin, there
      was nothing else of note in the medical history. Biomicroscopic examination
      showed papilledema with hemorrhages and cotton wool spots. The CSF opening
      pressure was initially > 50 cmH2O. During therapy by lumbar puncture (three
      times), oral carbonic anhydrase inhibitors and loop diuretics, the abducens nerve
      palsy and papilledema receded. Anticoagulation therapy (initially with coumarin
      derivatives, then with low molecular weight heparins) was unsuccessful in
      eliminating the thrombosis of the jugular vein. Surgical intervention was not
      recommended by the vascular surgeons. CONCLUSION: This case report demonstrates
      the unusual combination of (idiopathic) intracranial hypertension and thrombosis
      of the jugular vein, which occurred spontaneously and without any detectable
      coagulation disorders.

PMID- 25755027
TI  - Study of the sensitivity and resonant frequency of the torsional modes of an AFM
      cantilever with a sidewall probe based on a nonlocal elasticity theory.
AB  - A relationship based on a nonlocal elasticity theory is developed to investigate
      the torsional sensitivity and resonant frequency of an atomic force microscope
      (AFM) with assembled cantilever probe (ACP). This ACP comprises a horizontal
      cantilever and a vertical extension, and a tip located at the free end of the
      extension, which makes the AFM capable of topography at sidewalls of
      microstructures. First, the governing differential equations of motion and
      boundary conditions for dynamic analysis are obtained by a combination of the
      basic equations of nonlocal elasticity theory and Hamilton's principle.
      Afterward, a closed-form expression for the sensitivity of vibration modes has
      been obtained using the relationship between the resonant frequency and contact
      stiffness of cantilever and sample. These analysis accounts for a better
      representation of the torsional behavior of an AFM with sidewall probe where the
      small-scale effect are significant. The results of the proposed model are
      compared with those of classical beam theory. The results show that the
      sensitivities and resonant frequencies of ACP predicted by the nonlocal
      elasticity theory are smaller than those obtained by the classical beam theory.

PMID- 25755028
TI  - Regulation of functional expression of the electrogenic sodium bicarbonate
      cotransporter 1, NBCe1 (SLC4A4), in mouse astrocytes.
AB  - The electrogenic sodium bicarbonate cotransporter NBCe1 (SLC4A4) is expressed in
      many cell types and is a major regulator of intracellular, and extracellular pH.
      In astrocytes, membrane depolarization leads to intracellular alkalinization
      through the activation of NBCe1. However, the molecular mechanisms regulating
      functional expression of NBCe1 in astrocytes are largely unknown. Astrocytes also
      express voltage-dependent K(+) channels that are activated after depolarization
      and are sensitive to the K(+) blocker 4-aminopyridine (4AP). Using acute
      hippocampal slices and primary hippocampal and cortical astrocyte cultures, we
      have investigated the role of 4AP for the regulation of NBCe1 and elucidated the
      underlying signaling pathways by quantitative RT-PCR, immunoblotting,
      biotinylation of surface proteins, immunofluorescence, and intracellular H(+)
      recording using the H(+) -sensitive dye 2',7'-bis-(carboxyethyl)-5-(and-6)
      carboxyfluorescein. The results show significant upregulation of NBCe1
      transcript, protein, and surface expression after the application of 4AP in both
      hippocampal slices and astrocyte cultures, effects that were suppressed after the
      inhibition of c-jun N-terminal kinase (JNK), proto-oncogene tyrosine-protein
      kinase Src, and Src/extracellular-signal-regulated kinases signaling. In the
      presence of 4AP, the rate and amplitude of intracellular H(+) changes upon
      challenging NBCe1 increased in wild-type astrocytes but not in cortical
      astrocytes from NBCe1-deficient mice. 4AP-dependent effects were suppressed after
      the inhibition of JNK and Src signaling. Our results demonstrate that
      transcriptional regulation and targeting of NBCe1, as well as functional
      operation of NBCe1, may occur through multiple signaling pathways.

PMID- 25755029
TI  - Is exposure to secondhand smoke child abuse? Yes.

PMID- 25755030
TI  - Is exposure to secondhand smoke child abuse? No.

PMID- 25755031
TI  - Estimating the residency expansion required to avoid projected primary care
      physician shortages by 2035.
AB  - PURPOSE: The purpose of this study was to calculate the projected primary care
      physician shortage, determine the amount and composition of residency growth
      needed, and estimate the impact of retirement age and panel size changes.
      METHODS: We used the 2010 National Ambulatory Medical Care Survey to calculate
      utilization of ambulatory primary care services and the US Census Bureau to
      project demographic changes. To determine the baseline number of primary care
      physicians and the number retiring at 66 years, we used the 2014 American Medical
      Association Masterfile. Using specialty board and American Osteopathic
      Association figures, we estimated the annual production of primary care
      residents. To calculate shortages, we subtracted the accumulated primary care
      physician production from the accumulated number of primary care physicians
      needed for each year from 2015 to 2035. RESULTS: More than 44,000 primary care
      physicians will be needed by 2035. Current primary care production rates will be
      unable to meet demand, resulting in a shortage in excess of 33,000 primary care
      physicians. Given current production, an additional 1,700 primary care residency
      slots will be necessary by 2035. A 10% reduction in the ratio of population per
      primary care physician would require more than 3,000 additional slots by 2035,
      whereas changing the expected retirement age from 66 years to 64 years would
      require more than 2,400 additional slots. CONCLUSIONS: To eliminate projected
      shortages in 2035, primary care residency production must increase by 21%
      compared with current production. Delivery models that shift toward smaller
      ratios of population to primary care physicians may substantially increase the
      shortage.

PMID- 25755032
TI  - Timeliness of outpatient follow-up: an evidence-based approach for planning after
      hospital discharge.
AB  - PURPOSE: Timely outpatient follow-up has been promoted as a key strategy to
      reduce hospital readmissions, though one-half of patients readmitted within 30
      days of hospital discharge do not have follow-up before the readmission. Guidance
      is needed to identify the optimal timing of hospital follow-up for patients with
      conditions of varying complexity. METHODS: Using North Carolina Medicaid claims
      data for hospital-discharged patients from April 2012 through March 2013, we
      constructed variables indicating whether patients received follow-up visits
      within successive intervals and whether these patients were readmitted within 30
      days. We constructed 7 clinical risk strata based on 3M Clinical Risk Groups
      (CRGs) and determined expected readmission rates within each CRG. We applied
      survival modeling to identify groups that appear to benefit from outpatient
      follow-up within 3, 7, 14, 21, and 30 days after discharge. RESULTS: The final
      study sample included 44,473 Medicaid recipients with 65,085 qualifying
      discharges. The benefit of early follow-up varied according to baseline
      readmission risk. For example, follow-up within 14 days after discharge was
      associated with 1.5%-point reduction in readmissions in the lowest risk strata (P
      <.001) and a 19.1%-point reduction in the highest risk strata (P <.001). Follow
      up within 7 days was associated with meaningful reductions in readmission risk
      for patients with multiple chronic conditions and a greater than 20% baseline
      risk of readmission, a group that represented 24% of discharged patients.
      CONCLUSIONS: Most patients do not meaningfully benefit from early outpatient
      follow-up. Transitional care resources would be best allocated toward ensuring
      that highest risk patients receive follow-up within 7 days.

PMID- 25755033
TI  - Effect of continuity of care on hospital utilization for seniors with multiple
      medical conditions in an integrated health care system.
AB  - PURPOSE: Lower continuity of care has been associated with higher rates of
      adverse outcomes for persons with multiple chronic medical conditions. It is
      unclear, however, whether this relationship also exists within integrated systems
      that offer high levels of informational continuity through shared electronic
      health records. METHODS: We conducted a retrospective cohort study of 12,200
      seniors with 3 or more chronic conditions within an integrated delivery system.
      Continuity of care was calculated using the Continuity of Care Index, which
      reflects visit concentration with individual clinicians. Using Cox proportional
      hazards regression permitting continuity to vary monthly until the outcome or
      censoring event, we separately assessed inpatient admissions and emergency
      department visits as a function of primary care continuity and specialty care
      continuity. RESULTS: After adjusting for covariates (demographics; baseline,
      primary, and specialty care visits; baseline outcomes; and morbidity burden),
      greater primary care continuity and greater specialty care continuity were each
      associated with a lower risk of inpatient admission (respective hazard ratios
      (95% CIs) = 0.97 (0.96, 0.99) and 0.95 (0.93, 0.98)) and a lower risk of
      emergency department visits (respective hazard ratios = 0.97 (0.96, 0.98) and
      0.98 (0.96, 1.00)). For the subgroup with 3 or more primary care and 3 or more
      specialty care visits, specialty care continuity (but not primary care
      continuity) was independently associated with a decreased risk of inpatient
      admissions (hazard ratio = 0.94 (0.92, 0.97)), and primary care continuity (but
      not specialty care continuity) was associated with a decreased risk of emergency
      department visits (hazard ratio = 0.98 (0.96, 1.00)). CONCLUSIONS: In an
      integrated delivery system with high informational continuity, greater continuity
      of care is independently associated with lower hospital utilization for seniors
      with multiple chronic medical conditions. Different subgroups of patients will
      benefit from continuity with primary and specialty care clinicians depending on
      their care needs.

PMID- 25755034
TI  - Health coaching by medical assistants to improve control of diabetes,
      hypertension, and hyperlipidemia in low-income patients: a randomized controlled
      trial.
AB  - PURPOSE: Health coaching by medical assistants could be a financially viable
      model for providing self-management support in primary care if its effectiveness
      were demonstrated. We investigated whether in-clinic health coaching by medical
      assistants improves control of cardiovascular and metabolic risk factors when
      compared with usual care. METHODS: We conducted a 12-month randomized controlled
      trial of 441 patients at 2 safety net primary care clinics in San Francisco,
      California. The primary outcome was a composite measure of being at or below goal
      at 12 months for at least 1 of 3 uncontrolled conditions at baseline as defined
      by hemoglobin A1c, systolic blood pressure, and low-density lipoprotein (LDL)
      cholesterol. Secondary outcomes were meeting all 3 goals and meeting individual
      goals. Data were analyzed using chi(2) tests and linear regression models.
      RESULTS: Participants in the coaching arm were more likely to achieve both the
      primary composite measure of 1 of the clinical goals (46.4% vs 34.3%, P = .02)
      and the secondary composite measure of reaching all clinical goals (34.0% vs
      24.7%, P = .05). Almost twice as many coached patients achieved the hemoglobin
      A1c goal (48.6% vs 27.6%, P = .01). At the larger study site, coached patients
      were more likely to achieve the LDL cholesterol goal (41.8% vs 25.4%, P = .04).
      The proportion of patients meeting the systolic blood pressure goal did not
      differ significantly. CONCLUSIONS: Medical assistants serving as in-clinic health
      coaches improved control of hemoglobin A1c and LDL levels, but not blood
      pressure, compared with usual care. Our results highlight the need to understand
      the relationship between patients' clinical conditions, interventions, and the
      contextual features of implementation.

PMID- 25755035
TI  - Effects of primary care team social networks on quality of care and costs for
      patients with cardiovascular disease.
AB  - PURPOSE: Cardiovascular disease is the leading cause of mortality and morbidity
      in the United States. Primary care teams can be best suited to improve quality of
      care and lower costs for patients with cardiovascular disease. This study
      evaluates the associations between primary care team communication, interaction,
      and coordination (ie, social networks); quality of care; and costs for patients
      with cardiovascular disease. METHODS: Using a sociometric survey, 155 health
      professionals from 31 teams at 6 primary care clinics identified with whom they
      interact daily about patient care. Social network analysis calculated variables
      of density and centralization representing team interaction structures. Three
      level hierarchical modeling evaluated the link between team network density,
      centralization, and number of patients with a diagnosis of cardiovascular disease
      for controlled blood pressure and cholesterol, counts of urgent care visits,
      emergency department visits, hospital days, and medical care costs in the
      previous 12 months. RESULTS: Teams with dense interactions among all team members
      were associated with fewer hospital days (rate ratio [RR] = 0.62; 95% CI, 0.50
      0.77) and lower medical care costs (-$556; 95% CI, -$781 to -$331) for patients
      with cardiovascular disease. Conversely, teams with interactions revolving around
      a few central individuals were associated with increased hospital days (RR =
      1.45; 95% CI, 1.09-1.94) and greater costs ($506; 95% CI, $202-$810). Team-shared
      vision about goals and expectations mediated the relationship between social
      network structures and patient quality of care outcomes. CONCLUSIONS: Primary
      care teams that are more interconnected and less centralized and that have a
      shared team vision are better positioned to deliver high-quality cardiovascular
      disease care at a lower cost.

PMID- 25755036
TI  - Long-term effect of population screening for diabetes on cardiovascular
      morbidity, self-rated health, and health behavior.
AB  - PURPOSE: There is limited trial evidence concerning the long-term effects of
      screening for type 2 diabetes on population morbidity. We examined the effect of
      a population-based diabetes screening program on cardiovascular morbidity, self
      rated health, and health-related behaviors. METHODS: We conducted a pragmatic,
      parallel-group, cluster-randomized controlled trial of diabetes screening (the
      ADDITION-Cambridge study) including 18,875 individuals aged 40 to 69 years at
      high risk of diabetes in 32 general practices in eastern England (27 practices
      randomly allocated to screening, 5 to no-screening for control). Of those
      eligible for screening, 466 (2.9%) were diagnosed with diabetes. Seven years
      after randomization, a random sample of patients was sent a postal questionnaire:
      15% from the screening group (including diabetes screening visit attenders and
      non-attenders) and 40% from the no-screening control group. Self-reported
      cardiovascular morbidity, self-rated health (using the SF-8 Health Survey and EQ
      5D instrument), and health behaviors were compared between trial groups using an
      intention-to-screen analysis. RESULTS: Of the 3,286 questionnaires mailed out,
      1,995 (61%) were returned, with 1,945 included in the analysis (screening: 1,373;
      control: 572). At 7 years, there were no significant differences between the
      screening and control groups in the proportion of participants reporting heart
      attack or stroke (OR = 0.90, 95% CI, 0.71-1.15); SF-8 physical health summary
      score as an indicator of self-rated health status (beta -0.33, 95% CI, -1.80 to
      1.14); EQ-5D visual analogue score (beta: 0.80, 95% CI, -1.28 to 2.87); total
      physical activity (beta 0.50, 95% CI, -4.08 to 5.07); current smoking (OR 0.97,
      95% CI, 0.72 to 1.32); and alcohol consumption (beta 0.14, 95% CI, -1.07 to
      1.35). CONCLUSIONS: Invitation to screening for type 2 diabetes appears to have
      limited impact on population levels of cardiovascular morbidity, self-rated
      health status, and health behavior after 7 years.

PMID- 25755037
TI  - Predictors of chronic abdominal pain affecting the well-being of children in
      primary care.
AB  - PURPOSE: Abdominal pain is a frequent symptom among children but is rarely
      associated with organic disease. Although it may persist for years, no factors
      have been identified that predict its prognosis. Our aim was to determine whether
      patient characteristics at initial consultation can predict chronic abdominal
      pain severe enough to influence the child's well-being at 1 year of follow-up.
      METHODS: We conducted this prospective cohort study in primary care, including
      consecutive children aged 4 to 17 years seen for abdominal pain by their family
      physician. Multivariate logistic regression analysis was used to identify
      prognostic factors that predicted chronic abdominal pain 1 year later.
      Discriminative ability of identified predictors was assessed using the area under
      the receiver operating characteristic curve and explained variance. RESULTS: The
      risk of having chronic abdominal pain at 1 year of follow-up was 37.1% in the
      cohort overall. Increasing age, waking up at night with pain, high levels of
      other somatic complaints, and chronic abdominal pain at baseline independently
      predicted chronic abdominal pain at 1 year. These predictors had a poor to
      moderate discriminative ability, however; the area under the receiver operating
      characteristic curve was only 0.69, and the predictors collectively explained
      only 14.3% of variance in the development of chronic abdominal pain. The absolute
      risk ranged from 19.4% among children having none of the predictors to 65.5%
      among children having 3 or 4 predictors. CONCLUSIONS: Chronic abdominal pain
      sufficient to affect well-being is common among children initially seen for
      abdominal pain by family physicians. Although the risk of this outcome increases
      with number of predictors, these predictors are of limited value in identifying
      children in whom pain will become chronic, suggesting that other, as yet
      unidentified factors play an important role.

PMID- 25755038
TI  - Relationships of multimorbidity and income with hospital admissions in 3 health
      care systems.
AB  - Associations of multimorbidity and income with hospital admission were
      investigated in population samples from 3 widely differing health care systems:
      Scotland (n = 36,921), China (n = 162,464), and Hong Kong (n = 29,187).
      Multimorbidity increased odds of admissions in all 3 settings. In Scotland,
      poorer people were more likely to be admitted (adjusted odds ratio [aOR] = 1.62;
      95% CI, 1.41-1.86 for the lowest income group vs the highest), whereas China
      showed the opposite (aOR = 0.58; 95% CI, 0.56-0.60). In Hong Kong, poorer people
      were more likely to be admitted to public hospitals (aOR = 1.68; 95% CI, 1.36
      2.07), but less likely to be admitted to private ones (aOR = 0.18; 95% CI, 0.13
      0.25). Strategies to improve equitable health care should consider the impact of
      socioeconomic deprivation on the use of health care resources, particularly among
      populations with prevalent multimorbidity. 

PMID- 25755039
TI  - Recommendations for a mixed methods approach to evaluating the patient-centered
      medical home.
AB  - PURPOSE: There is a strong push in the United States to evaluate whether the
      patient-centered medical home (PCMH) model produces desired results. The
      explanatory and contextually based questions of how and why PCMH succeeds in
      different practice settings are often neglected. We report the development of a
      comprehensive, mixed qualitative-quantitative evaluation set for researchers,
      policy makers, and clinician groups. METHODS: To develop an evaluation set, the
      Brown Primary Care Transformation Initiative convened a multidisciplinary group
      of PCMH experts, reviewed the PCMH literature and evaluation strategies,
      developed key domains for evaluation, and selected or created methods and
      measures for inclusion. RESULTS: The measures and methods in the evaluation set
      (survey instruments, PCMH meta-measures, patient outcomes, quality measures,
      qualitative interviews, participant observation, and process evaluation) are
      meant to be used together. PCMH evaluation must be sufficiently comprehensive to
      assess and explain both the context of transformation in different primary care
      practices and the experiences of diverse stakeholders. In addition to commonly
      assessed patient outcomes, quality, and cost, it is critical to include PCMH
      components integral to practice culture transformation: patient and family
      centeredness, authentic patient activation, mutual trust among practice employees
      and patients, and transparency, joy, and collaboration in delivering and
      receiving care in a changing environment. CONCLUSIONS: This evaluation set offers
      a comprehensive methodology to enable understanding of how PCMH transformation
      occurs in different practice settings. This approach can foster insights about
      how transformation affects critical outcomes to achieve meaningful, patient
      centered, high-quality, and cost-effective sustainable change among diverse
      primary care practices.

PMID- 25755041
TI  - You can't hide the bridges.
AB  - After witnessing a man commit suicide during residency, I struggled to reconcile
      the trauma itself, my own competence, and multiple boundary issues I was
      exploring as a newly minted doctor. My powerlessness in the face of inevitability
      challenged my sense of capability to fulfill the very calling that brought me
      into medicine in the beginning-to help fix important problems in the lives of my
      patients. In the aftermath, I chose to remain connected to the experience in the
      way I honor him still today. 

PMID- 25755040
TI  - Why medical schools are tolerant of unethical behavior.
AB  - The exposure to unethical and unprofessional behavior is thought to play a major
      role in the declining empathy experienced by medical students during their
      training. We reflect on the reasons why medical schools are tolerant of unethical
      behavior of faculty. First, there are barriers to reporting unprofessional
      behavior within medical schools including fear of retaliation and lack of
      mechanisms to ensure anonymity. Second, deans and directors do not want to look
      for unethical behavior in their colleagues. Third, most of us have learned to
      take disrespectful circumstances in health care institutions for granted. Fourth,
      the accreditation of medical schools around the world does not usually cover the
      processes or outcomes associated with fostering ethical behavior in students.
      Several initiatives promise to change that picture. 

PMID- 25755042
TI  - A prescription to advocate for graduate medical education reform.

PMID- 25755043
TI  - PBRNS discuss utilizing big data for research and within a learning health
      system.

PMID- 25755044
TI  - New guideline covers labor, vaginal birth after cesarean.

PMID- 25755045
TI  - Kendall M. Campbell, MD selected as 2014 Puffer/IOM fellow.

PMID- 25755046
TI  - Creating leaders in family medicine.

PMID- 25755047
TI  - Building research capacity in departments of family medicine: pearls from NAPCRG
      2013.

PMID- 25755049
TI  - Fractional carbon dioxide laser in recalcitrant vulval lichen sclerosus.
AB  - Vulval lichen sclerosus is an uncommon skin condition that can usually be managed
      with topical corticosteroids to maintain remission. However, there is a subset of
      patients in whom it remains recalcitrant despite treatment with super-potent
      topical corticosteroids. We report a case series of four patients undergoing
      fractional carbon dioxide laser resurfacing and one with ablative carbon dioxide
      laser for severe, hyperkeratotic vulval lichen sclerosus not responding to super
      potent topical corticosteroids. In these patients, carbon dioxide laser was
      successful in achieving remission. Their vulval lichen sclerosus was subsequently
      able to be maintained with topical corticosteroid treatment. 

PMID- 25755050
TI  - N-terminal guanidinylation of the cyclic 1,4-ureido-deltorphin analogues: the
      synthesis, receptor binding studies, and resistance to proteolytic digestion.
AB  - The synthesis of a series of N-guanidinylated cyclic ureidopeptides, analogues of
      1,4-ureido-deltorphin/dermorphine tetrapeptide is described. The delta- and MU
      opioid receptor affinity of new guanidinylated analogues and their non
      guanidinylated precursors was determined by the displacement radioligand binding
      experiments. Our results indicate that the guanidinylation of cyclic 1,4
      ureidodeltorphin peptide analogues does not exhibit a uniform influence on the
      opioid receptor binding properties, similarly as reported earlier for some linear
      peptides. All analogues were also tested for their in vitro resistance to
      proteolysis during incubation with large excess of chymotrypsin, pepsin, and
      papain by means of mass spectroscopy. Guanidinylated ureidopeptides 1G-4G showed
      mixed MU agonist/delta agonist properties and high enzymatic stability indicating
      their potential as therapeutic agents for treatment of pain.

PMID- 25755051
TI  - Curcumin induces apoptotic cell death via Oct4 inhibition and GSK-3beta
      activation in NCCIT cells.
AB  - SCOPE: Octamer-binding transcription factor 4 (Oct4) is a key regulator of
      pluripotent embryonic stem cell maintenance. However, increasing evidence has
      suggested that Oct4 is also expressed in cancer stem cells (CSCs) and is
      associated with tumor progression and chemoresistance. Curcumin (CUR) is a widely
      used cancer chemopreventive agent, and it has been used to treat several diseases
      including cancers. Here, we investigated whether CUR-induced apoptotic cell death
      by inhibiting Oct4 levels and examining molecular mechanisms in NCCIT human
      embryonic carcinoma cells. METHODS AND RESULTS: CUR significantly inhibited Oct4
      transcription levels in a dose-dependent manner by dual luciferase experiment,
      also decreased mRNA and protein levels in NCCIT human embryonic carcinoma cells,
      which express high levels of endogenous Oct4. Interestingly, we found that CUR
      treatment increased apoptotic cell death including subG0/G1 contents, cleavage
      caspases, and pro-apoptotic protein, as confirmed with a series of loss-of
      function experiments using Oct4 siRNA. Furthermore, CUR induced marked total
      level of glycogen synthase kinase 3 beta (GSK-3beta), resulting in an increase in
      apoptotic cell death, was evaluated using chemical inhibitor of GSK3-3beta.
      CONCLUSION: These data suggest that CUR induces apoptotic cell death through Oct4
      inhibition and GSK-3beta activation. Thus, CUR may be a useful cancer
      chemopreventive agent to suppress tumor progression or to improve chemoresistance
      by eliminating CSCs.

PMID- 25755052
TI  - In vitro characterization of the bioconversion of pomaglumetad methionil, a novel
      metabotropic glutamate 2/3 receptor agonist peptide prodrug.
AB  - To characterize the hydrolysis of the peptide prodrug pomaglumetad methionil
      (LY2140023; (1R,4S,5S,6S)-4-(L-methionylamino)-2-thiabicyclo[3.1.0]hexane-4,6
      dicarboxylic acid 2,2-dioxide), to the active drug LY404039 [(1R,4S,5S,6S)-4
      amino-2-thiabicyclo[3.1.0]hexane-4,6-dicarboxylic acid 2,2-dioxide], a series of
      in vitro studies were performed in various matrices, including human intestinal,
      liver, kidney homogenate, and human plasma. The studies were performed to
      determine the tissue(s) and enzyme(s) responsible for the conversion of the
      prodrug to the active molecule. This could enable an assessment of the risk for
      drug interactions, an evaluation of pharmacogenomic implications, as well as the
      development of a Physiologically Based Pharmacokinetic (PBPK) model for formation
      of the active drug. Of the matrices examined, hydrolysis of pomaglumetad
      methionil was observed in intestinal and kidney homogenate preparations and
      plasma, but not in liver homogenate. Clearance values calculated after applying
      standard scaling factors suggest the intestine and kidney as primary sites of
      hydrolysis. Studies with peptidase inhibitors were performed in an attempt to
      identify the enzyme(s) catalyzing the conversion. Near complete inhibition of
      LY404039 formation was observed in intestinal and kidney homogenate and human
      plasma with the selective dehydropeptidase1 (DPEP1) inhibitor cilastatin. Human
      recombinant DPEP1 was expressed and shown to catalyze the hydrolysis, which was
      completely inhibited by cilastatin. These studies demonstrate pomaglumetad
      methionil can be converted to LY404039 via one or multiple enzymes completely
      inhibited by cilastatin, likely DPEP1, in plasma, the intestine, and the kidney,
      with the plasma and kidney involved in the clearance of the circulating prodrug.
      These experiments define a strategy for the characterization of enzymes
      responsible for the metabolism of other peptide-like compounds. 

PMID- 25755053
TI  - cis-Cyclopropylamines as mechanism-based inhibitors of monoamine oxidases.
AB  - Cyclopropylamines, inhibitors of monoamine oxidases (MAO) and lysine-specific
      demethylase (LSD1), provide a useful structural scaffold for the design of
      mechanism-based inhibitors for treatment of depression and cancer. For new
      compounds with the less common cis relationship and with an alkoxy substituent at
      the 2-position of the cyclopropyl ring, the apparent affinity determined from
      docking experiments revealed little difference between the enantiomers. Using the
      racemate, kinetic parameters for the reversible and irreversible inhibition of
      MAO were determined. No inhibition of LSD1 was observed. For reversible
      inhibition, most compounds gave high IC50 values with MAO A, but sub-micromolar
      values with MAO B. After pre-incubation of the cyclopropylamine with the enzyme,
      the inhibition was irreversible for both MAO A and MAO B, and the activity was
      not restored by dilution. Spectral changes during inactivation of MAO A included
      bleaching at 456 nm and an increased absorbance at 400 nm, consistent with flavin
      modification. These derivatives are MAO B-selective irreversible inhibitors that
      do not show inhibition of LSD1. The best inhibitor was cis-N-benzyl-2
      methoxycyclopropylamine, with an IC50 of 5 nm for MAO B and 170 nm for MAO A
      after 30 min pre-incubation. This cis-cyclopropylamine is over 20-fold more
      effective than tranylcypromine, so may be studied as a lead for selective
      inhibitors of MAO B that do not inhibit LSD1.

PMID- 25755054
TI  - High altitude may affect cardiac structure in smoking subjects.

PMID- 25755055
TI  - Prevalence and characteristics of true and apparent treatment resistant
      hypertension in the Campania Salute Network.

PMID- 25755056
TI  - Multiple hormone deficiencies in chronic heart failure.

PMID- 25755057
TI  - Munchausen syndrome presented as recurrent syncope.

PMID- 25755058
TI  - Changes in BNP and cardiac troponin I after high-intensity interval and endurance
      exercise in heart failure patients and healthy controls.

PMID- 25755059
TI  - Chronic kidney disease has a significant impact on platelet inhibition of new
      P2Y12 inhibitors.

PMID- 25755060
TI  - Does endurance exercise cause atrial fibrillation in women?

PMID- 25755061
TI  - Angiographic and clinical results of everolimus-eluting stent utilization in
      saphenous vein graft lesions (ARES).

PMID- 25755062
TI  - Macrophage phenotypic plasticity in atherosclerosis: The associated features and
      the peculiarities of the expression of inflammatory genes.
AB  - Macrophages are essential players in induction and progression of atherosclerotic
      inflammation. The complexity of macrophage phenotypes was observed in human
      plaques and atherosclerotic lesions in mouse models of atherosclerosis. Plaque
      macrophages were shown to exhibit a phenotypic range that is intermediate between
      two extremes, M1 (pro-inflammatory) and M2 (anti-inflammatory). Indeed, in
      atherosclerosis, macrophages demonstrate phenotypic plasticity to rapidly adjust
      to changing microenvironmental conditions. In the plaque, serum lipids, serum
      lipoproteins and various pro- or anti-inflammatory stimuli such as cytokines,
      chemokines and small bioactive molecules could greatly influence the macrophage
      phenotype inducing switch towards more proinflammatory or anti-inflammatory
      properties. Dynamic plasticity of macrophages is achieved by up-regulation and
      down-regulation of an overlapping set of transcription factors that drive
      macrophage polarization. Understanding of mechanisms of macrophage plasticity and
      resolving functional characteristics of distinct macrophage phenotypes should
      help in the development of new strategies for treatment of chronic inflammation
      in atherosclerosis and other cardiovascular diseases. 

PMID- 25755063
TI  - Safety and efficacy of intracoronary hypoxia-preconditioned bone marrow
      mononuclear cell administration for acute myocardial infarction patients: The
      CHINA-AMI randomized controlled trial.
AB  - BACKGROUND: Pre-clinical studies have shown that hypoxia preconditioning can
      enhance stem cell therapeutic potential for myocardial repair. We sought to
      investigate the safety and feasibility of intracoronary administration of hypoxia
      preconditioned bone marrow mononuclear cells (HP-BMCs) for acute ST segment
      elevation myocardial infarction (STEMI). METHODS: We randomized 22 patients with
      acute STEMI to receive intracoronary administration of normoxia bone marrow
      mononuclear cells (N-BMCs) (n=11) or HP-BMCs (n=11) following successful
      reperfusion. Another 14 patients receiving standard therapy were recruited as
      control (n=14). RESULTS: There were no differences in the occurrence of major
      adverse cardiovascular events at 30 days and 1 year among three groups. There
      were significant improvement in the change of left ventricular end-diastolic
      volume (LVEDV) and end-systolic volume (LVESV) in HP-BMC group both at 6 and 12
      months compared with N-BMCs or control group (P<0.05). No differences were
      observed in the change of left ventricular ejection fraction (LVEF), or wall
      motion score index (WMSI) among three groups. Nevertheless, WMSI was improved in
      HP-BMCs and N-BMC group (P<0.05, within group), but not in control. The ratio of
      myocardial perfusion defect determined by SPECT was significantly decreased in HP
      BMCs and N-BMC groups at 6months compared with baseline (P<0.05, within group),
      but no significant differences were observed among three groups. CONCLUSIONS: Our
      results provide the first-in-man evidence that intracoronary administration of HP
      BMCs following acute MI appears to be safe and feasible. These results provide
      the basis for future prospective randomized clinical trials in a larger patient
      cohort. CLINICAL TRIAL REGISTRATION INFORMATION: NCT01234181
      (http://clinicaltrials.gov/ct2/show/NCT01234181?term=NCT01234181&rank=1).

PMID- 25755064
TI  - Telemedicine for cardiovascular disease continuum: A position paper from the
      Italian Society of Cardiology Working Group on Telecardiology and Informatics.
AB  - Telemedicine is the provision of health care services, through the use of
      information and communication technology, in situations where the health care
      professional and the patient, or 2 health care professionals, are not in the same
      location. It involves the secure transmission of medical data and information,
      through text, sound, images, or other forms needed for the prevention, diagnosis,
      treatment, and follow-up of a patient. First data on implementation of
      telemedicine for the diagnosis and treatment of acute myocardial infarction date
      from more than 10 years ago. Telemedicine has a potential broad application to
      the cardiovascular disease continuum and in many branches of cardiology, at least
      including heart failure, ischemic heart disease and arrhythmias. Telemedicine
      might have an important role as part of a strategy for the delivery of effective
      health care for patients with cardiovascular disease. In this document the
      Working Group on Telecardiology and Informatics of the Italian Society of
      Cardiology intends to remark some key-points regarding potential benefit
      achievable with the implementation of telemedicine support in the continuum of
      cardiovascular disease.

PMID- 25755065
TI  - Comparative reproducibility of TELOSTM and GNRB(r) for instrumental measurement
      of anterior tibial translation in normal knees.
AB  - BACKGROUND: TELOSTM is among the reference tools for the instrumental measurement
      of anterior tibial translation during the initial work-up and follow-up of
      patients with injuries to the anterior cruciate ligament (ACL). GRNB((r)) is a
      non-irradiating but recently developed tool for which only limited data are
      available. HYPOTHESIS: The GRNB((r)) offers better reproducibility than TELOSTM
      for measuring anterior tibial translation without rotation in normal knees.
      MATERIAL AND METHODS: We retrospectively evaluated instrumental laxity
      measurements in normal knees. Data were available for 60 TELOSTM measurements
      (9kg load) and 57 GNRB((r)) measurements (89N and 134N loads). For each
      instrument, we compared the absolute variation in anterior tibial translation
      between two measurements performed 6 months apart. For each GNRB((r))
      measurement, patellar pressure was recorded. RESULTS: No significant differences
      were found between mean (+/- SD) variations in translation between the two
      instruments. A greater than 2.5mm variation between the two measurements was
      significantly more common with TELOSTM than with GRNB((r)) (P<0.05, Chi(2) test).
      GRNB((r)) translation values did not correlate with patellar pressure.
      DISCUSSION: The GNRB((r)) device offers greater reproducibility than TELOSTM when
      used to quantitate anterior tibial translation. The limited sample size may have
      prevented the detection of a significant difference between mean values. In
      addition, disadvantages of the TELOSTM include radiation exposure of the patient,
      operator-dependency of measurements made on the radiographs, and absence of a
      biofeedback system to limit hamstring contraction. GNRB((r)) does have hamstring
      contraction biofeedback control but uses another parameter, namely, patellar
      pressure, for which the optimal value is unknown. Quadriceps and hamstring co
      contraction induced by excessive patellar pressure may influence anterior tibial
      translation. The optimal patellar pressure value needs to be determined.

PMID- 25755066
TI  - Femoral lengthening during hip resurfacing arthroplasty: a new surgical
      procedure.
AB  - Correction of leg length discrepancy during hip arthroplasty is a technical
      challenge. Although resurfacing proposed to young subjects presents a number of
      advantages (stability, bone stock, etc.), it does not correct leg length
      discrepancy. We propose an original femoral lengthening technique concomitant to
      resurfacing performed through the same approach, consisting in a Z-shaped
      subtrochanteric osteotomy. Resurfacing was performed first and the femoral and
      acetabular reaming material was used for autografting. The series comprised five
      cases followed for a mean 42.2 months (range, 33-64 months). The mean surgical
      time was 100 min (range, 76-124 min). Weightbearing was authorized in all cases
      at the 8th week. The mean lengthening was 32 mm (range, 25-40 mm). Healing was
      observed in all cases. This surgical technique, reserved for very young subjects
      who accept an 8-week postoperative period without weightbearing, can be proposed
      in cases with substantial preoperative leg length discrepancy.

PMID- 25755067
TI  - Pullout characteristics of percutaneous pedicle screws with different cement
      augmentation methods in elderly spines: An in vitro biomechanical study.
AB  - BACKGROUND: Vertebroplasty prefilling or fenestrated pedicle screw augmentation
      can be used to enhance pullout resistance in elderly patients. It is not clear
      which method offers the most reliable fixation strength if axial pullout and a
      bending moment is applied. The purpose of this study is to validate a new in
      vitro model aimed to reproduce a cut out mechanism of lumbar pedicle screws, to
      compare fixation strength in elderly spines with different cement augmentation
      techniques and to analyze factors that might influence the failure pattern.
      MATERIALS AND METHODS: Six human specimens (82-100 years) were instrumented
      percutaneously at L2, L3 and L4 by non-augmented screws, vertebroplasty
      augmentation and fenestrated screws. Cement distribution (2 ml PMMA) was analyzed
      on CT. Vertebral endplates and the rod were oriented at 45 degrees  to the
      horizontal plane. The vertebral body was held by resin in a cylinder, linked to
      an unconstrained pivot, on which traction (10 N/s) was applied until rupture.
      Load-displacement curves were compared to simultaneous video recordings. RESULTS:
      Median pullout forces were 488.5 N (195-500) for non-augmented screws, 643.5 N
      (270-1050) for vertebroplasty augmentation and 943.5 N (750-1084) for fenestrated
      screws. Cement augmentation through fenestrated screws led to significantly
      higher rupture forces compared to non-augmented screws (P=0.0039). The pullout
      force after vertebroplasty was variable and linked to cement distribution. A
      cement bolus around the distal screw tip led to pullout forces similar to non
      augmented screws. A proximal cement bolus, as it was observed in fenestrated
      screws, led to higher pullout resistance. This cement distribution led to
      vertebral body fractures prior to screw pullout. CONCLUSION: The experimental
      setup tended to reproduce a pullout mechanism observed on radiographs, combining
      axial pullout and a bending moment. Cement augmentation with fenestrated screws
      increased pullout resistance significantly, whereas the fixation strength with
      the vertebroplasty prefilling method was linked to the cement distribution.

PMID- 25755068
TI  - Tantalum cones and bone defects in revision total knee arthroplasty.
AB  - Management of bone loss is a major challenge in revision total knee arthroplasty
      (TKA). The development of preformed porous tantalum cones offers new
      possibilities, because they seem to have biological and mechanical qualities that
      facilitate osseointegration. Compared to the original procedure, when metaphyseal
      bone defects are too severe, a single tantalum cone may not be enough and we have
      developed a technique that could extend the indications for this cone in these
      cases. We used 2 cones to fill femoral bone defects in 7 patients. There were no
      complications due to wear of the tantalum cones. Radiological follow-up did show
      any migration or loosening. The short-term results confirm the interest of porous
      tantalum cones and suggest that they can be an alternative to allografts or
      megaprostheses in case of massive bone defects. 

PMID- 25755069
TI  - Gcn5 Modulates the Cellular Response to Oxidative Stress and Histone Deacetylase
      Inhibition.
AB  - To identify chemical genetic interactions underlying the mechanism of action of
      histone deacetylase inhibitors (HDACi) a yeast deletion library was screened for
      hypersensitive deletion mutants that confer increased sensitivity to the HDACi,
      CG-1521. The screen demonstrated that loss of GCN5 or deletion of components of
      the Gcn5 histone acetyltransferase (HAT) complex, SAGA, sensitizes yeast to CG
      1521-induced cell death. Expression profiling after CG-1521 treatment reveals
      increased expression of genes involved in metabolism and oxidative stress
      response, and oxidative stress response mutants are hypersensitive to CG-1521
      treatment. Accumulation of reactive oxygen species and increased cell death are
      enhanced in the gcn5Delta deletion mutant, and are abrogated by anti-oxidants,
      indicating a central role of oxidative stress in CG-1521-induced cell death. In
      human cell lines, siRNA mediated knockdown of GCN5 or PCAF, or chemical
      inhibition of GCN5 enzymatic activity, increases the sensitivity to CG-1521 and
      SAHA. These data suggest that the combination of HDAC and GCN5/PCAF inhibitors
      can be used for cancer treatment.

PMID- 25755070
TI  - Carbon Dots: The Newest Member of the Carbon Nanomaterials Family.
AB  - Carbon nanomaterials have been extensively researched in the past few years owing
      to their interesting properties. The massive research efforts resulted in the
      emergence of carbon dots, which belong to the carbon nanomaterials family. Carbon
      dots (C-dots) have garnered the attention of researchers mainly due to their
      convenient availability from organic as well as inorganic materials and also due
      to the novel properties they exhibit. C-Dots have been said to overcome the era
      of quantum dots, referring to their levels of toxicity and biocompatibility. In
      this review, we focus on the discovery of C-dots, their structure and
      composition, surface passivation to enhance their optical properties, the various
      synthetic methods used, their applications in different areas, and future
      perspectives. Emphasis has been given to greener approaches for the synthesis of
      C-dots in order to make them cost effective as well as to improve their
      biocompatibility. 

PMID- 25755071
TI  - Coherent control of optical polarization effects in metamaterials.
AB  - Processing of photonic information usually relies on electronics. Aiming to avoid
      the conversion between photonic and electronic signals, modulation of light with
      light based on optical nonlinearity has become a major research field and
      coherent optical effects on the nanoscale are emerging as new means of handling
      and distributing signals. Here we demonstrate that in slabs of linear material of
      sub-wavelength thickness optical manifestations of birefringence and optical
      activity (linear and circular birefringence and dichroism) can be controlled by a
      wave coherent with the wave probing the polarization effect. We demonstrate this
      in proof-of-principle experiments for chiral and anisotropic microwave
      metamaterials, where we show that the large parameter space of polarization
      characteristics may be accessed at will by coherent control. Such control can be
      exerted at arbitrarily low intensities, thus arguably allowing for fast handling
      of electromagnetic signals without facing thermal management and energy
      challenges. 

PMID- 25755072
TI  - Photocatalytic direct conversion of ethanol to 1,1- diethoxyethane over noble
      metal-loaded TiO2 nanotubes and nanorods.
AB  - As one of the most important biomass platform molecules, ethanol needs to have
      its product chain chemically extended to meet future demands in renewable fuels
      and chemicals. Additionally, chemical conversion of ethanol under mild and green
      conditions is still a major challenge. In this work, ethanol is directly
      converted into 1,1-diethoxyethane (DEE) and H2 under mild photocatalytic
      conditions over platinum-loaded TiO2 nanotubes and nanorods. The reaction follows
      a tandem dehydrogenation-acetalization mechanism, in which ethanol is first
      dehydrogenated into acetaldehyde and H(+) ion by photogenerated holes, and then
      acetalization between acetaldehyde and ethanol proceeds through promotion by H(+)
      ions formed in real time. Excess H(+) ions are simultaneously reduced into H2 by
      photogenerated electrons. This photocatalytic process has a very high reaction
      rate over nanosized tubular and rod-like TiO2 photocatalysts, reaching 157.7 mmol
      g(-1)  h(-1) in relatively low photocatalyst feeding. More importantly, the
      reaction is highly selective, with a nearly stoichiometric conversion of reacted
      ethanol into DEE. This photocatalytic dehydrogenation C?O coupling of ethanol is
      a new green approach to the direct efficient conversion of ethanol into DEE and
      provides a promising channel for sustainable bioethanol applications. 

PMID- 25755073
TI  - Application of a liquid chromatographic/tandem mass spectrometric method to a
      urinary excretion study of rabeprazole and two of its metabolites in healthy
      human urine.
AB  - To study urinary excretion properties of rabeprazole and two of its metabolites,
      i.e. rabeprazole thioether and desmethyl rabeprazole thioether in human urine, a
      sensitive, selective, accurate and precise method for the quantification of
      rabeprazole and two of its metabolites using a liquid chromatographic/tandem mass
      spectrometric method has been developed and validated. Starting with a 200 MUL
      urine aliquot, a general sample preparation was performed using protein
      precipitation with methanol. Analytes were separated on a Dikma InspireTM C18
      column (150 mm * 2.1mm, 5 MUm) using a mixture of methanol and aqueous 10mM
      ammonium acetate buffer containing 0.05% formic acid (55:45, v/v) as mobile
      phase. Linearity was obtained over the concentration range of 0.1446-96.38 ng/mL,
      0.3198-319.8 ng/mL and 0.05160-82.53 ng/mL for rabeprazole, rabeprazole
      thioether, desmethyl rabeprazole thioether in human urine, respectively. The
      fully validated method was applied to a urine excretion study of rabeprazole
      sodium administered as a 30 min intravenous infusion for the first time. The
      calculated cumulative urinary recovery just reached 0.047450/00, 1.2720/00 and
      0.16310/00 of dose within 24h post-dose for rabeprazole, rabeprazole thioether,
      and desmethyl rabeprazole thioether, respectively, after intravenous infusion
      administration, indicating that rabeprazole and its two main metabolites undergo
      substantial non-renal elimination in healthy Chinese volunteers.

PMID- 25755074
TI  - Stress and coping in parents of children with Prader-Willi syndrome: Assessment
      of the impact of a structured plan of care.
AB  - Hyperphagia, developmental delays, and maladaptive behaviors are common in Prader
      Willi syndrome (PWS) likely resulting in heightened parental stress. Objectives
      were to evaluate stress, describe usefulness of coping behaviors, and assess the
      impact of a structured Plan of Care (PC) on parents with children with PWS.
      Parents answered Perceived Stress Scale (PSS-14), Coping Health Inventory for
      Parents (CHIP), and narrative/demographic surveys. The PC was introduced to a
      cohort of parents after completion of the PSS-14 and CHIP and re-administered 4-6
      month after the introduction of the PC. Higher parental stress (n = 57) was
      observed compared to the general population, and associated with parent's age,
      number of children living at home, and child's age and residential setting.
      "Maintaining family integration, cooperation, and an optimistic definition of the
      situation" was the most useful coping pattern. Thirty-eight parents answered the
      PSS-14 and CHIP after the PC. Parental stress decreased after the PC (P = 0.035).
      Coping behaviors related to "maintaining family integration" increased after the
      PC (P = 0.042). Women and men preferred different coping patterns before and
      after the PC. In conclusion, parental stress is increased in PWS, and a PC
      decreased stress and increased coping behaviors related to family stability for
      parents with children with PWS.

PMID- 25755075
TI  - Maternal prepregnancy obesity and achievement of infant motor developmental
      milestones in the upstate KIDS study.
AB  - OBJECTIVE: Maternal prepregnancy obesity is associated with several poor infant
      health outcomes; however, studies that investigated motor development have been
      inconsistent. Thus, maternal prepregnancy weight status and infants' gross motor
      development were examined. METHODS: Participants consisted of 4,901 mother-infant
      pairs from the Upstate KIDS study, a longitudinal cohort in New York. Mothers
      indicated dates when infants achieved each of six gross motor milestones when
      infants were 4, 8, 12, 18, and 24 months old. Failure time modeling under a
      Weibull distribution was utilized to compare time to achievement across three
      levels of maternal prepregnancy BMI. Hazard ratios (HR) below one indicate a
      lower "risk" of achieving the milestone and translate to later achievement.
      RESULTS: Compared to infants born to thin and normal-weight mothers (BMI < 25),
      infants born to mothers with obesity (BMI > 30) were slower to sit without
      support (HR = 0.91, P = 0.03) and crawl on hands and knees (HR = 0.86, P <
      0.001), after adjusting for maternal and birth characteristics. Increased
      gestational age was associated with faster achievement of all milestones, but
      additional adjustment did not impact results. CONCLUSIONS: Maternal prepregnancy
      obesity was associated with a slightly longer time for infant to sit and crawl,
      potentially due to a compromised intrauterine environment or reduced physically
      active play.

PMID- 25755076
TI  - Characterization of the nocardiopsin biosynthetic gene cluster reveals
      similarities to and differences from the rapamycin and FK-506 pathways.
AB  - Macrolide-pipecolate natural products, such as rapamycin (1) and FK-506 (2), are
      renowned modulators of FK506-binding proteins (FKBPs). The nocardiopsins, from
      Nocardiopsis sp. CMB-M0232, are the newest members of this structural class.
      Here, the biosynthetic pathway for nocardiopsins A-D (4-7) is revealed by
      cloning, sequencing, and bioinformatic analyses of the nsn gene cluster. In vitro
      evaluation of recombinant NsnL revealed that this lysine cyclodeaminase catalyzes
      the conversion of L-lysine into the L-pipecolic acid incorporated into 4 and 5.
      Bioinformatic analyses supported the conjecture that a linear nocardiopsin
      precursor is equipped with the hydroxy group required for macrolide closure in a
      previously unobserved manner by employing a P450 epoxidase (NsnF) and limonene
      epoxide hydrolase homologue (NsnG). The nsn cluster also encodes candidates for
      tetrahydrofuran group biosynthesis. The nocardiopsin pathway provides
      opportunities for engineering of FKBP-binding metabolites and for probing new
      enzymology in nature's polyketide tailoring arsenal. 

PMID- 25755077
TI  - Radioiodine remnant ablation in low-risk differentiated thyroid cancer patients
      who had R0 dissection is an over treatment.
AB  - Low-risk (LR) differentiated thyroid cancer (DTC) patients should be ablated or
      not, albeit, with small dose of radioiodine is highly controversial. We
      hypothesized that those LR DTC patients who were surgically ablated need no
      radioiodine remnant ablation (RRA). This study aims to evaluate the long-term
      outcome in these two groups of patients. Retrospective cohort study conducted
      from January 1991 to December 2012. Based on extent of surgical resection and
      histopathology, LR DTC patients were classified as Gr-1: 169 patients, who were
      surgically ablated; Gr-2: 153 patients, who had significant remnant in thyroid
      bed. Basal parameters were comparable between two groups except pretherapy 24 h
      radioiodine uptake (0.16 +/- 0.01% vs. 5.64 +/- 0.46%; P < 0.001). No patient
      received RRA in Gr-1; Gr-2 patients were administered 30 mCi (131) I. Total
      number of events (recurrence, persistent, and progression of disease), with
      median follow up of 10.3 years, was observed in 10/322 (3.1%) of LR DTC patients.
      Only one patient had disease recurrence from Gr-1, who became disease-free after
      radioiodine therapy. Similarly, one patient from 126, who was ablated with single
      dose of RRA, had recurrence from Gr-2. However, 8/27 (29.7%) patients from Gr-2
      had persistent disease; even two of them subsequently developed disease
      progression, who failed first-dose of RRA. The event-free survival rates were
      99.4% and 94.1% (P = 0.006) in Gr-1 and Gr-2, respectively. RRA is an
      overtreatment in surgically ablated LR DTC patients. Successfully ablated RRA
      patients also had similar long-term outcome, however, those who failed, should be
      re-stratified as intermediate-risk category, and managed aggressively. 

PMID- 25755078
TI  - Host litter-associated gut dynamics affect Escherichia coli abundance and
      adhesion genotype in rats.
AB  - The probability of detecting Escherichia coli varies between host species with
      different diets and body sizes. An experimental study that mimicked the effect of
      different carnivore body masses found that digesta transit times influence E.
      coli abundance. In this study, we investigated how the host's gastrointestinal
      dynamics affected E. coli abundance and genotype in a system that reflected an
      herbivorous host. Forty rats from nine litters were fed a diet high in
      fermentable fibre. We found a small effect of fibre concentration on the
      difference between the liquid and particle digesta retention times. However, the
      rats' litter membership explained the majority of the retention time differences
      (79%). In turn, we found that as the difference between liquid and particle
      retention times increased, E. coli faecal cell densities decreased, while the
      likelihood that an animal's dominant E. coli strain possessed a gene involved in
      adhesion (agn43) increased. Thus, this experiment revealed an unanticipated high
      degree of association between the hosts' litter, their gastrointestinal dynamics
      and the E. coli genotypes. Furthermore, by comparing our findings to previous
      work, we show that the presence of fermentable fibre in the diet appears to
      change the relationship between the host's phenotype and E. coli. 

PMID- 25755079
TI  - Zinc supplementation influences genomic stability biomarkers, antioxidant
      activity, and zinc transporter genes in an elderly Australian population with low
      zinc status.
AB  - SCOPE: An increased intake of Zinc (Zn) may reduce the risk of degenerative
      diseases but may prove to be toxic if taken in excess. This study aimed to
      investigate whether zinc carnosine supplement can improve Zn status, genome
      stability events, and Zn transporter gene expression in an elderly (65-85 years)
      South Australian cohort with low plasma Zn levels. METHODS AND RESULTS: A 12-week
      placebo-controlled intervention trial was performed with 84 volunteers completing
      the study, (placebo, n = 42) and (Zn group, n = 42). Plasma Zn was significantly
      increased (p < 0.05) by 5.69% in the Zn supplemented group after 12 weeks. A
      significant (p < 0.05) decrease in the micronucleus frequency (-24.18%) was
      observed for the Zn supplemented cohort relative to baseline compared to the
      placebo group. Reductions of -7.09% for tail moment and -8.76% for tail intensity
      were observed for the Zn group (relative to baseline) (p < 0.05). Telomere base
      damage was found to be also significantly decreased in the Zn group (p < 0.05).
      Both MT1A and ZIP1 expression showed a significant increase in the Zn
      supplemented group (p < 0.05). CONCLUSION: Zn supplementation may have a
      beneficial effect in an elderly population with low Zn levels by improving Zn
      status, antioxidant profile, and lowering DNA damage.

PMID- 25755080
TI  - Contamination pathways of spore-forming bacteria in a vegetable cannery.
AB  - Spoilage of low-acid canned food during prolonged storage at high temperatures is
      caused by heat resistant thermophilic spores of strict or facultative bacteria.
      Here, we performed a bacterial survey over two consecutive years on the
      processing line of a French company manufacturing canned mixed green peas and
      carrots. In total, 341 samples were collected, including raw vegetables, green
      peas and carrots at different steps of processing, cover brine, and process
      environment samples. Thermophilic and highly-heat-resistant thermophilic spores
      growing anaerobically were counted. During vegetable preparation, anaerobic spore
      counts were significantly decreased, and tended to remain unchanged further
      downstream in the process. Large variation of spore levels in products
      immediately before the sterilization process could be explained by occasionally
      high spore levels on surfaces and in debris of vegetable combined with long
      residence times in conditions suitable for growth and sporulation. Vegetable
      processing was also associated with an increase in the prevalence of highly-heat
      resistant species, probably due to cross-contamination of peas via blanching
      water. Geobacillus stearothermophilus M13-PCR genotypic profiling on 112 isolates
      determined 23 profile-types and confirmed process-driven cross-contamination.
      Taken together, these findings clarify the scheme of contamination pathway by
      thermophilic spore-forming bacteria in a vegetable cannery. 

PMID- 25755081
TI  - Estimation of the growth kinetic parameters of Bacillus cereus spores as affected
      by pulsed light treatment.
AB  - Quantitative microbial risk assessment requires the knowledge of the effect of
      food preservation technologies on the growth parameters of the survivors of the
      treatment. This is of special interest in the case of the new non-thermal
      technologies that are being investigated for minimal processing of foods. This is
      a study on the effect of pulsed light technology (PL) on the lag phase of
      Bacillus cereus spores surviving the treatment and the maximum growth rate
      (MUmax) of the survivors after germination. The D value was estimated as 0.35
      J/cm(2) and our findings showed that PL affected the kinetic parameters of the
      microorganism. A log linear relationship was observed between the lag phase and
      the intensity of the treatment. Increasing the lethality lengthened the mean lag
      phase and proportionally increased its variability. A polynomial regression was
      fitted between the MUmax of the survivors and the inactivation achieved. The
      MUmax decreased as intensity increased. From these data, and their comparison to
      published results on the effect of heat and e-beam irradiation on B. cereus
      spores, it was observed that the shelf-life of PL treated foods would be longer
      than those treated with heat and similar to irradiated ones. These findings offer
      information of interest for the implementation of PL for microbial
      decontamination in the food industry.

PMID- 25755082
TI  - Efficacy and possible mechanisms of perillaldehyde in control of Aspergillus
      niger causing grape decay.
AB  - A variety of plant products have been recognized for their antifungal activity
      and recently have attracted food industry attention for their efficacy in
      controlling postharvest fungal decay of fruits. The antifungal activity of
      perillaldehyde (PAE) was evaluated against Aspergillus niger, a known cause of
      grape spoilage, and possible mechanisms were explored. PAE showed notable
      antifungal activity against A. niger, with a minimum inhibitory concentration
      (MIC) and a minimum fungicidal concentration (MFC) of 0.25 and 1 MUl/ml,
      respectively. The accumulation of mycelial biomass was also inhibited by PAE in a
      dose-dependent manner, completely inhibiting mycelial growth at 1 MUl/ml. In vivo
      data confirmed that the vapour treatment of grapes with various concentrations of
      PAE markedly improved control of A. niger and suppressed natural decay.
      Concentrations of PAE of 0.075 MUl/ml air showed the greatest inhibition of
      fungal growth compared to the controls. Further experiments indicated that PAE
      activated a membrane-active mechanism that inhibits ergosterol synthesis,
      increases membrane permeability (as evidenced by extracellular pH and
      conductivity measurements), and disrupts membrane integrity, leading to cell
      death. Our findings suggest that this membrane-active mechanism makes PAE a
      promising potential antifungal agent for postharvest control of grape spoilage.

PMID- 25755085
TI  - beta-Functionalized Push-Pull Porphyrin Sensitizers in Dye-Sensitized Solar
      Cells: Effect of pi-Conjugated Spacers.
AB  - A series of new beta-functionalized push-pull-structured porphyrin dyes were
      synthesized so as to investigate the effect of the pi-conjugated spacer on the
      performance of dye-sensitized solar cells (DSSCs). Suzuki- and Heck-type
      palladium-catalyzed coupling methodologies were used to obtain various beta
      functionalized porphyrins and beta-benzoic acid (ZnPHn) and beta-vinylbenzoic
      acid (ZnPVn) derivatives from beta-borylated porphyrin precursors. Photophysical
      studies of the resulting porphyrins revealed a clear dependence on the nature of
      the beta linker. In particular, it was found that a beta-vinylene linkage
      perturbs the electronic structure of the porphyrin core; this is less true for a
      beta-phenyl linkage. Theoretical analyses provided support for the intrinsic
      intramolecular charge-transfer character of the beta-functionalized, push-pull
      porphyrins of this study. The extent of charge transfer depends on the nature of
      the beta-conjugated linkage. The photovoltaic performances of the cells
      sensitized with beta-phenylenevinylene ZnPVn exhibited higher power conversion
      efficiency values than those bearing beta-phenyl linkages (ZnPHn). This was
      ascribed to differences in light-harvesting efficiency. Furthermore, compared to
      the use of a standard iodine-based electrolyte, the DSSC performance of cells
      made from the present porphyrins was improved by more than 1 % upon using a
      cobalt(II/III)-based electrolyte. Under standard AM 1.5 illumination, the highest
      efficiency, 8.2 %, was obtained by using cells made from the doubly beta
      butadiene-linked porphyrin. 

PMID- 25755084
TI  - Insulin response to oral stimuli and glucose effectiveness increased in
      neuroglycopenia following gastric bypass.
AB  - OBJECTIVE: Hyperinsulinemic hypoglycemia with neuroglycopenia is a rare
      complication following Roux-en-Y gastric bypass (RYGB) surgery for weight
      management. Insulin secretion and action in response to oral and intravenous
      stimuli in persons with and without neuroglycopenia following RYGB are evaluated
      in this study. METHODS: Cross-sectional cohort studies were performed at a single
      academic institution to assess insulin secretion and action during oral mixed
      meal tolerance test and intravenous glucose tolerance test (IVGTT). RESULTS:
      Insulin secretion was increased more following oral mixed meal than intravenous
      glucose in individuals with neuroglycopenia compared to the asymptomatic group.
      Reduced insulin clearance did not contribute to higher insulinemia. Glucose
      effectiveness at zero insulin, estimated during the IVGTT, was also higher in
      those with neuroglycopenia. Insulin sensitivity did not differ between groups.
      CONCLUSIONS: Increased beta-cell response to oral stimuli and insulin-independent
      glucose disposal may both contribute to severe hypoglycemia after RYGB.

PMID- 25755086
TI  - My Research History on the Chemical Standpoint-From Molecular Structure to
      Surface Science.
AB  - The structure of molecules using gas electron diffraction (GED) was my graduate
      study. However, I was making a new apparatus for precise measurements by GED and
      formulated a scheme for the least-squares analysis for a smooth continuous curve
      of scattering intensity. My research was completely shifted to the solid surface
      after moving to Gakushuin University, where I briefly studied the liquid
      structure of CCl4 molecules, and I then moved to the Institute for Solid State
      Physics, the University of Tokyo. My studies of surface science were focused on
      the electronic properties and related phenomena, and various experimental methods
      were developed. The plasmon dispersions elucidated the initial oxidation of
      aluminum and one-dimensional metal on Si(001)2 * 1-K. Irreversible phase
      transition was discovered on MgO(001) using the LEED Kikuchi pattern. The
      electronic structure of the dislocation was observed on MgO(001) by the electron
      time-of-flight method. The phase transition on Si(001) and the rotational epitaxy
      in a K monoatomic layer on Cu(001) were found. Next, I changed to studies of the
      dynamical phenomena on the surface, where very low energy reactive ion scattering
      on metal surfaces and laser-induced desorption caused by electronic transition of
      NO and CO molecules from metal surfaces were observed, and the hydrogen atom
      location at the surface and interface was measured with a high depth resolution
      using a resonance nuclear reaction of (1) H + (15) N(2+) at 6.385 MeV. Finally, I
      moved to the University of Electro-Communications and studied thin single-crystal
      oxide layers on transition metals, in which the band-gap narrowing was found, and
      then a Pt monoatomic layer was prepared on the alpha-Al(2)O(3) film.

PMID- 25755083
TI  - Neurodegeneration severity can be predicted from early microglia alterations
      monitored in vivo in a mouse model of chronic glaucoma.
AB  - Microglia serve key homeostatic roles, and respond to neuronal perturbation and
      decline with a high spatiotemporal resolution. The course of all chronic CNS
      pathologies is thus paralleled by local microgliosis and microglia activation,
      which begin at early stages of the disease. However, the possibility of using
      live monitoring of microglia during early disease progression to predict the
      severity of neurodegeneration has not been explored. Because the retina allows
      live tracking of fluorescent microglia in their intact niche, here we
      investigated their early changes in relation to later optic nerve
      neurodegeneration. To achieve this, we used the DBA/2J mouse model of inherited
      glaucoma, which develops progressive retinal ganglion cell degeneration of
      variable severity during aging, and represents a useful model to study pathogenic
      mechanisms of retinal ganglion cell decline that are similar to those in human
      glaucoma. We imaged CX3CR1(+/GFP) microglial cells in vivo at ages ranging from 1
      to 5 months by confocal scanning laser ophthalmoscopy (cSLO) and quantified cell
      density and morphological activation. We detected early microgliosis at the optic
      nerve head (ONH), where axonopathy first manifests, and could track attenuation
      of this microgliosis induced by minocycline. We also observed heterogeneous and
      dynamic patterns of early microglia activation in the retina. When the same
      animals were aged and analyzed for the severity of optic nerve pathology at 10
      months of age, we found a strong correlation with the levels of ONH microgliosis
      at 3 to 4 months. Our findings indicate that live imaging and monitoring the time
      course and levels of early retinal microgliosis and microglia activation in
      glaucoma could serve as indicators of future neurodegeneration severity.

PMID- 25755087
TI  - Twenty-five additional cases of trisomy 9 mosaic: Birth information, medical
      conditions, and developmental status.
AB  - Limited literature exists on children and adults diagnosed with the mosaic form
      of trisomy 9. Data from the Tracking Rare Incidence Syndromes (TRIS) project has
      provided physical characteristics and medical conditions for 14 individuals. This
      article provides TRIS Survey results of 25 additional cases at two data points
      (birth and survey completion) as well as developmental status. Results confirmed
      a number of phenotypic features and medical conditions. In addition, a number of
      cardiac anomalies were reported along with feeding and respiratory difficulties
      in the immediate postnatal period. In addition, developmental status data
      indicated a range in functioning level up to skills in the 36 and 48-month range.
      Strengths were also noted across the sample in language and communication, fine
      motor and social-emotional development. Implications for professionals caring for
      children with this genetic condition are offered.

PMID- 25755088
TI  - NlpI-mediated modulation of outer membrane vesicle production through
      peptidoglycan dynamics in Escherichia coli.
AB  - Outer membrane vesicles (OMVs) are ubiquitously secreted from the outer membrane
      (OM) of Gram-negative bacteria. These heterogeneous structures are composed of OM
      filled with periplasmic content from the site of budding. By analyzing mutants
      that have vesicle production phenotypes, we can gain insight into the mechanism
      of OMV budding in wild-type cells, which has thus far remained elusive. In this
      study, we present data demonstrating that the hypervesiculation phenotype of the
      nlpI deletion mutant of Escherichia coli correlates with changes in peptidoglycan
      (PG) dynamics. Our data indicate that in stationary phase cultures the nlpI
      mutant exhibits increased PG synthesis that is dependent on spr, consistent with
      a model in which NlpI controls the activity of the PG endopeptidase Spr. In log
      phase, the nlpI mutation was suppressed by a dacB mutation, suggesting that NlpI
      regulates penicillin-binding protein 4 (PBP4) during exponential growth. The data
      support a model in which NlpI negatively regulates PBP4 activity during log
      phase, and Spr activity during stationary phase, and that in the absence of NlpI,
      the cell survives by increasing PG synthesis. Further, the nlpI mutant exhibited
      a significant decrease in covalent outer membrane (OM-PG) envelope stabilizing
      cross-links, consistent with its high level of OMV production. Based on these
      results, we propose that one mechanism wild-type Gram-negative bacteria can use
      to modulate vesiculation is by altering PG-OM cross-linking via localized
      modulation of PG degradation and synthesis. 

PMID- 25755089
TI  - Diallyl disulfide inhibits growth and metastatic potential of human triple
      negative breast cancer cells through inactivation of the beta-catenin signaling
      pathway.
AB  - SCOPE: Although diallyl disulfide (DADS), an important garlic (Allium sativum)
      derivative, has exhibited potential anticancer activity, the molecular mechanism
      of this activity remains unknown. In this study, we evaluated the antitumor
      activity of DADS in triple-negative breast cancer (TNBC) cell lines based in
      vitro and in vivo models. METHODS AND RESULTS: We found that treatment with DADS
      resulted in decreased viability, increased apoptosis, and suppression of
      metastatic potential in TNBC cells. Furthermore, DADS induced dysregulation of B
      cell lymphoma (Bcl)-2 family members, downregulation of matrix metalloproteinase
      (MMP)-9 and reversal of the epithelial-mesenchymal transition (EMT).
      Interestingly, DADS significantly inhibited activation of the beta-catenin
      signaling pathway, which regulated Bcl-2 family members, MMP-9 and EMT in TNBC
      cells. Consistent with these in vitro findings, we also verified the anticancer
      potential of DADS in MDA-MB-231 xenograft mice. Treatment with DADS significantly
      reduced tumor volume and weight and increased apoptosis in these mice, while the
      expression of active beta-catenin was decreased, and the downstream molecules
      were dysregulated. CONCLUSION: Our results show that the antitumor effect of DADS
      on TNBC cells is mediated by the beta-catenin pathway, suggesting that DADS could
      be used as a potential therapeutic agent for treating or preventing breast
      cancer.

PMID- 25755090
TI  - Spectral imaging to measure heterogeneity in membrane lipid packing.
AB  - Physicochemical properties of the plasma membrane have been shown to play an
      important role in cellular functionality. Among those properties, the molecular
      order of the lipids, or the lipid packing, is of high importance. Changes in
      lipid packing are believed to compartmentalize cellular signaling by initiating
      coalescence and conformational changes of proteins. A common way to infer
      membrane lipid packing is by using membrane-embedded polarity-sensitive dyes,
      whose emission spectrum is dependent on the molecular order of the immediate
      membrane environment. Here, we report on an improved determination of such
      spectral shifts in the emission spectrum of the polarity-sensitive dyes. This
      improvement is based on the use of spectral imaging on a scanning confocal
      fluorescence microscope in combination with an improved analysis, which considers
      the whole emission spectrum instead of just single wavelength ranges. Using this
      approach and the polarity-sensitive dyes C-Laurdan or Di-4-ANEPPDHQ, we were able
      to image-with high accuracy-minute differences in the lipid packing of model and
      cellular membranes. 

PMID- 25755091
TI  - Prevalence and correlates of adult overweight in the Muslim world: analysis of 46
      countries.
AB  - The primary objectives of the study were to calculate overweight prevalence (body
      mass index >= 25.0) and simple correlations between 10 demographic, social
      welfare and behavioural variables and overweight prevalence for Muslim countries
      (populations >50% Muslim; N = 46). Overweight data for a country's total, male
      and female populations were extracted from the World Health Organization's (WHO)
      STEPwise country reports and relevant publications. Country-level data for
      potential correlates were extracted from multiple sources: Central Intelligence
      Agency (literacy), Gallup Poll (religiosity), United Nations (agricultural
      employment, food supply, gender inequality, human development), World Bank
      (automobile ownership, Internet, labour force) and WHO (physical inactivity). The
      overall, male and female overweight prevalence was 37.4, 33.0 and 42.1%,
      respectively. Prevalence estimates significantly differed by economic
      classification, gender and ethnicity. Middle- and upper income countries were
      1.54-7.76 (95% confidence interval [CI]: 1.49-8.07) times more likely overweight
      than low-income countries, females were 1.48 (CI: 1.45-1.50) times more likely
      overweight than males and Arab countries were 2.92 (CI: 2.86-2.97) times more
      likely overweight than non-Arab countries. All 10 of the potential correlates
      were significantly associated with overweight for at least one permutation
      (total, economic classification, gender, ethnicity). The greater percentage of
      poorer countries among non-Arab Muslim countries, which compared with Arab
      countries have not as rapidly been transformed by globalization, nutrition
      transition and urbanization, may partially explain prevalence differences.
      Evaluation of correlational data generally followed associations seen in non
      Muslim countries but more complex analysis of subnational data is needed. Arab
      women are a particularly vulnerable subgroup and governments should act within
      religious and cultural parameters to provide environments that are conducive to
      negative energy balance. 

PMID- 25755092
TI  - Plasma cholesterol-lowering and transient liver dysfunction in mice lacking
      squalene synthase in the liver.
AB  - Squalene synthase (SS) catalyzes the biosynthesis of squalene, the first specific
      intermediate in the cholesterol biosynthetic pathway. To test the feasibility of
      lowering plasma cholesterol by inhibiting hepatic SS, we generated mice in which
      SS is specifically knocked out in the liver (L-SSKO) using Cre-loxP technology.
      Hepatic SS activity of L-SSKO mice was reduced by >90%. In addition, cholesterol
      biosynthesis in the liver slices was almost eliminated. Although the hepatic
      squalene contents were markedly reduced in L-SSKO mice, the hepatic contents of
      cholesterol and its precursors distal to squalene were indistinguishable from
      those of control mice, indicating the presence of sufficient centripetal flow of
      cholesterol and/or its precursors from the extrahepatic tissues. L-SSKO mice
      showed a transient liver dysfunction with moderate hepatomegaly presumably
      secondary to increased farnesol production. In a fed state, the plasma total
      cholesterol and triglyceride were significantly reduced in L-SSKO mice, primarily
      owing to reduced hepatic VLDL secretion. In a fasted state, the hypolipidemic
      effect was lost. mRNA expression of liver X receptor alpha target genes was
      reduced, while that of sterol-regulatory element binding protein 2 target genes
      was increased. In conclusion, liver-specific ablation of SS inhibits hepatic
      cholesterol biosynthesis and induces hypolipidemia without increasing significant
      mortality. 

PMID- 25755094
TI  - Across the board: Brent H. Shanks.

PMID- 25755093
TI  - Usual breakfast eating habits affect response to breakfast skipping in overweight
      women.
AB  - OBJECTIVE: This randomized, cross-over trial was designed to investigate the
      metabolic and appetitive responses to skipping breakfast in overweight women who
      were habitual breakfast Eaters or Skippers. METHODS: Nine Eaters and nine
      Skippers were studied on two separate days during which subjects ate breakfast
      (B) or had no breakfast (NB), followed by a standard lunch meal 4 h later. Blood
      sampling for hormones and metabolites was performed after lunch, and appetite was
      rated throughout the day. RESULTS: Interactions between day and habitual
      breakfast pattern were seen for area under the curve (AUC) for insulin and free
      fatty acids (FFA). Both insulin (P = 0.020) and FFA (P = 0.023) AUC were higher
      on the NB day for Eaters but similar on both days for Skippers. Eaters had higher
      pre lunch hunger AUC on the NB day (P = 0.015) as well as lower pre lunch satiety
      AUC under both conditions (P = 0.019). CONCLUSIONS: Overall, this study showed
      that the adverse effects of skipping breakfast (higher insulin and FFA responses
      to lunch, increased hunger, and decreased satiety) were found primarily in
      habitual breakfast eaters. This suggests that meal skipping may have enhanced
      effects in habitual Eaters due to entrainment of metabolic and appetitive
      regulatory systems.

PMID- 25755095
TI  - Fetal brain disruption sequence versus fetal brain arrest: A distinct autosomal
      recessive developmental brain malformation phenotype.
AB  - The term fetal brain disruption sequence (FBDS) was coined to describe a number
      of sporadic conditions caused by numerous external disruptive events presenting
      with variable imaging findings. However, rare familial occurrences have been
      reported. We describe five patients (two sib pairs and one sporadic) with
      congenital severe microcephaly, seizures, and profound intellectual disability.
      Brain magnetic resonance imaging (MRI) revealed unique and uniform picture of
      underdeveloped cerebral hemispheres with increased extraxial CSF, abnormal gyral
      pattern (polymicrogyria-like lesions in two sibs and lissencephaly in the
      others), loss of white matter, dysplastic ventricles, hypogenesis of corpus
      callosum, and hypoplasia of the brainstem, but hypoplastic cerebellum in one.
      Fetal magnetic resonance imaging (FMRI) of two patients showed the same
      developmental brain malformations in utero. These imaging findings are in
      accordance with arrested brain development rather than disruption. Molecular
      analysis excluded mutations in potentially related genes such as NDE1, MKL2,
      OCLN, and JAM3. These unique clinical and imaging findings were described before
      among familial reports with FBDS. However, our patients represent a recognizable
      phenotype of developmental brain malformations, that is, apparently
      distinguishable from either familial microhydranencephaly or microlissencephaly
      that were collectively termed FBDS. Thus, the use of the umbrella term FBDS is no
      longer helpful. Accordingly, we propose the term fetal brain arrest to
      distinguish them from other familial patients diagnosed as FBDS. The presence of
      five affected patients from three unrelated consanguineous families suggests an
      autosomal-recessive mode of inheritance. The spectrum of fetal brain disruption
      sequence is reviewed.

PMID- 25755097
TI  - Inhibitory effect of dietary capsaicin on liver fibrosis in mice.
AB  - SCOPE: Virtually all chronic liver injuries result in the activation of hepatic
      stellate cells (HSCs). In their activated state, these cells are the main
      collagen-producing cells implicated in liver fibrosis. Capsaicin (CPS), the
      active compound of chili peppers, can modulate the activation and migration of
      HSCs in vitro. Here, we evaluated the potential protective and prophylactic
      effects of CPS related to cholestatic and hepatotoxic-induced liver fibrosis and
      its possible underlying mechanism of action. METHODS AND RESULTS: Male Balb/c
      mice received dietary CPS after 3 days of bile duct ligation (BDL) or before and
      during carbon tetrachloride (CCl4 ) injections. Mice receiving dietary CPS after
      BDL had a significant improvement of liver fibrosis accompanied by a decrease in
      collagen deposition and downregulation of activation markers in isolated HSCs. In
      the CCl4 model, dietary CPS inhibited the upregulation of profibrogenic markers.
      However, CPS could not attenuate the CCl4 -induced fibrosis when it was already
      established. Furthermore, in vitro CPS treatment inhibited the autophagic process
      during HSC activation. CONCLUSION: Dietary CPS has potential benefits in the
      therapy of cholestatic liver fibrosis and in the prophylaxis of hepatotoxic
      induced liver injury.

PMID- 25755098
TI  - Signals and mechanics shaping compartment boundaries in Drosophila.
AB  - During animal development groups of cells with similar fates and functions often
      stay together and separate from cells with different fates. An example for this
      cellular behavior is the formation of compartments, groups of cells with similar
      fates that are separated by sharp boundaries from neighboring groups of cells.
      Compartments play important roles during patterning by serving as units of growth
      and gene expression. Boundaries between compartments are associated with
      organizers that secrete signaling molecules instructing growth and
      differentiation throughout the tissue. The straight shape of the boundary between
      compartments is important for maintaining the position and shape of the organizer
      and thus for precise patterning. The straight shape of compartment boundaries,
      however, is challenged by cell divisions and cell intercalations that take place
      in many developing tissues. Early work established a role for selector genes and
      signaling pathways in setting up and keeping boundaries straight. Recent work in
      Drosophila has now begun to further unravel the physical and cellular mechanisms
      that maintain compartment boundaries. Key to the separation of compartments is a
      local increase of actomyosin-dependent mechanical tension at cell junctions along
      the boundary. Increased mechanical tension acts as a barrier to cell mixing
      during cell division and influences cell rearrangements during cell
      intercalations along the compartment boundary in a way that the straight shape of
      the boundary is maintained. An important question for the future is how the
      signaling pathways that maintain the straight shape of compartment boundaries
      control mechanical tension along these boundaries.

PMID- 25755096
TI  - The antifungal plant defensin AhPDF1.1b is a beneficial factor involved in
      adaptive response to zinc overload when it is expressed in yeast cells.
AB  - Antimicrobial peptides represent an expanding family of peptides involved in
      innate immunity of many living organisms. They show an amazing diversity in their
      sequence, structure, and mechanism of action. Among them, plant defensins are
      renowned for their antifungal activity but various side activities have also been
      described. Usually, a new biological role is reported along with the discovery of
      a new defensin and it is thus not clear if this multifunctionality exists at the
      family level or at the peptide level. We previously showed that the plant
      defensin AhPDF1.1b exhibits an unexpected role by conferring zinc tolerance to
      yeast and plant cells. In this paper, we further explored this activity using
      different yeast genetic backgrounds: especially the zrc1 mutant and an UPRE-GFP
      reporter yeast strain. We showed that AhPDF1.1b interferes with adaptive cell
      response in the endoplasmic reticulum to confer cellular zinc tolerance. We thus
      highlighted that, depending on its cellular localization, AhPDF1.1b exerts quite
      separate activities: when it is applied exogenously, it is a toxin against fungal
      and also root cells, but when it is expressed in yeast cells, it is a peptide
      that modulates the cellular adaptive response to zinc overload. 

PMID- 25755099
TI  - Anti-fibrotic Role of miR-214 in Thioacetamide-induced Liver Cirrhosis in Rats.
AB  - An increasing number of studies have focused on the role of microRNAs in liver
      fibrosis/cirrhosis. miR-214 has recently attracted more attention as a fibrosis
      related factor; however, the molecular mechanisms in hepatic fibrogenesis remain
      largely unknown. Here, we investigate the pathological role of miR-214 during
      progression of liver cirrhosis in rats. Rats were injected intraperitoneally with
      thioacetamide at a dose of 100 mg/kg body weight, twice a week. The liver was
      collected at post first injection weeks 5, 10, 15, and 20. Hepatic expression of
      miR-214 was analyzed by real-time polymerase chain reaction, in situ
      hybridization, and laser microdissection. The effects of miR-214 overexpression
      were investigated by in vitro transfection using fibroblastic MT-9 cells. miR-214
      was highly upregulated in the fibrotic area in parallel with the cirrhosis
      progression. miR-214 overexpression in MT-9 cells under transforming growth
      factor-beta1 stimulation resulted in decreased cell number and increased
      expression of cleaved caspase 3 and decreased expression of alpha-smooth muscle
      actin, suggesting that miR-214 induces apoptosis and inhibits myofibroblast
      differentiation in fibroblastic cells under stimulation of fibrogenic factors.
      These data indicate an anti-fibrotic role of miR-214 in chemically induced liver
      fibrosis/cirrhosis. 

PMID- 25755100
TI  - Occurrence of Pineal Gland Tumors in Combined Chronic Toxicity/Carcinogenicity
      Studies in Wistar Rats.
AB  - Pineal gland tumors are very rare brain lesions in rats as well as in other
      species including humans. A total of 8 (out of 1,360 examined) Wistar rats from 3
      different combined chronic toxicity/carcinogenicity or mere carcinogenicity
      studies revealed pineal gland tumors. The tumors were regarded to be spontaneous
      and unrelated to treatment. The morphology and immunohistochemical evaluation led
      to the diagnosis malignant pinealoma. The main characteristics that were variably
      developed within the tumors were the following: cellular atypia, high mitotic
      index, giant cells, necrosis, Homer Wright rosettes, Flexner-Wintersteiner
      rosettes and pseudorosettes, positive immunohistochemical reaction for
      synaptophysin, and neuron-specific enolase. The pineal gland is not a protocol
      organ for histopathological examination in carcinogenicity studies. Nevertheless,
      the pineal gland can occasionally be encountered on the routine brain section or
      if it is the origin of a tumor protruding into the brain, the finding will be
      recorded. Therefore, although known to be a rare tumor in rats, pineal neoplasms
      should be included in the list of possible differential diagnoses for brain
      tumors, especially when the tumor is located in the region of the pineal body. 

PMID- 25755101
TI  - Regulatory Forum Opinion Piece: Blinding and Binning in Histopathology Methods in
      the Biomarker Qualification Process.
AB  - Both, the Society of Toxicologic Pathology (STP) and the U.S. Food and Drug
      Administration (FDA) have released documents discussing histopathology methods in
      biomarker qualification studies. These documents appear to disagree on two
      critical and controversial aspects of methodology; blinding of pathologists and
      binning of data (Burkhardt et al. 2011; U.S. FDA 2011). Upon closer examination,
      however, both documents propose that blinded evaluation of biomarker studies is
      appropriate under similar strict criteria. However, they differ in their
      recommendations on the binning of data (i.e., individual binning of all changes
      vs. common binning of changes observed in control animals), seemingly based on
      different perceptions of study objectives and the role of the pathologist. This
      article offers a personal opinion on blinded evaluations and data binning in the
      context of biomarker qualification studies. 

PMID- 25755102
TI  - Chemotherapy for advanced poorly differentiated pancreatic neuroendocrine
      carcinoma.
AB  - Pancreatic neuroendocrine carcinoma (P-NEC) resembles small cell lung carcinoma
      in its biologic and clinical features, such as rapid growth and relatively high
      sensitivity to platinum-based chemotherapy. And, etoposide plus cisplatin (EP) or
      irinotecan plus cisplatin (IP), recommended by guidelines for the treatment of
      small cell lung carcinoma, has also been widely used for the treatment of
      unresectable NEC. Both regimens have been demonstrated to show favorable efficacy
      and have been acknowledged as de facto standard regimens for unresectable NEC,
      although it remains unclear which of the two regimens might yield more favorable
      outcomes. Therefore, a phase III trial of EP vs. IP has been planned for
      unresectable gastrointestinal, hepatobiliary or pancreatic NEC by the Japan
      Clinical Oncology Group. For patients with unresectable NEC who are refractory or
      intolerant to these regimens, no standard regimens have been established.
      Everolimus, an mTOR inhibitor, is likely to be effective in such patients, as
      there have been sporadic reports of the usefulness of everolimus in the treatment
      of P-NEC. A multicenter phase II trial is underway to elucidate the efficacy and
      safety of everolimus in patients with P-NEC who are refractory or intolerant to
      EP or IP. 

PMID- 25755103
TI  - Genome-wide mapping of TnrA-binding sites provides new insights into the TnrA
      regulon in Bacillus subtilis.
AB  - Under nitrogen limitation conditions, Bacillus subtilis induces a sophisticated
      network of adaptation responses. More precisely, the B. subtilis TnrA regulator
      represses or activates directly or indirectly the expression of a hundred genes
      in response to nitrogen availability. The global TnrA regulon have already been
      identified among which some directly TnrA-regulated genes have been
      characterized. However, a genome-wide mapping of in vivo TnrA-binding sites was
      still needed to clearly define the set of genes directly regulated by TnrA. Using
      chromatin immunoprecipitation coupled with hybridization to DNA tiling arrays
      (ChIP-on-chip), we now provide in vivo evidence that TnrA reproducibly binds to
      42 regions on the chromosome. Further analysis with real-time in vivo
      transcriptional profiling, combined with results from previous reports, allowed
      us to define the TnrA primary regulon. We identified 35 promoter regions
      fulfilling three criteria necessary to be part of this primary regulon: (i) TnrA
      binding in ChIP-on-chip experiments and/or in previous in vitro studies; (ii) the
      presence of a TnrA box; (iii) TnrA-dependent expression regulation. In addition,
      the TnrA primary regulon delimitation allowed us to improve the TnrA box
      consensus. Finally, our results reveal new interconnections between the nitrogen
      regulatory network and other cellular processes. 

PMID- 25755104
TI  - Speech and language in a genotyped cohort of individuals with Kabuki syndrome.
AB  - Speech and language deficits are commonly associated with Kabuki syndrome. Yet
      little is known regarding the specific symptomatology of these disorders,
      preventing use of targeted treatment programs. Here we detail speech and language
      in 16 individuals with Kabuki syndrome (thirteen with KMT2D mutations, one with a
      KDM6A mutation, and two mutation-negative cases), aged 4-21 years. The most
      striking speech deficit was dysarthria, characterised by imprecise consonants,
      harsh vocal quality, hypernasality, reduced rate and stress, and distorted pitch.
      Oromotor functioning was also impaired. Delayed, rather than disordered,
      articulation and phonology was common. Both receptive and expressive language
      abilities were reduced in the majority and deficits were noted across all
      language sub-domains (i.e., semantics, syntax, morphology, and pragmatics) with
      no clear differentiation or specific language profile. Individuals with Kabuki
      syndrome present with a heterogenous pattern of oromotor, speech, and language
      deficits. This variability fits with the multisystem nature of the disorder,
      which may encompass neurological, orofacial structural, hearing, and cognitive
      deficits, any or all of which may contribute to speech or language impairment.
      Our results suggest that all individuals with Kabuki syndrome have some level of
      communication deficit, warranting speech pathology involvement in all cases.

PMID- 25755105
TI  - Facile and Scalable Synthesis of Novel Spherical Au Nanocluster
      Assemblies@Polyacrylic Acid/Calcium Phosphate Nanoparticles for Dual-Modal
      Imaging-Guided Cancer Chemotherapy.
AB  - Engineering novel theranostic agents with both imaging and therapeutic functions
      have profound impact on molecular diagnostics, imaging, and therapeutics. In this
      paper, we develop for the first time a simple, scalable, and reproducible route
      to synthesize novel multifunctional spherical Au nanoclusters assemblies
      encapsulated by a polyacylic acid (PAA)/calcium phosphate (CaP) shell with
      aggregation enhanced fluorescence property (designated as AuNCs-A@PAA/CaP).
      Furthermore, the resulting AuNCs-A@PAA/CaP nanoparticles (NPs) possess a high
      payload of doxorubicin as synergetic pH-sensitive drug delivery vehicles to
      employ for dual-modal computed tomography (CT) and fluorescence imaging-guided
      liver cancer chemotherapy in vivo. The results reveal that AuNCs-A@PAA/CaP NPs
      not only provide excellent bimodal CT and fluorescence contrast imaging but also
      present efficient tumor ablation under the guidance of CT and fluorescence
      imaging, to achieve excellent chemotherapeutic efficacy to the hepatocarcinoma
      cell line (H-22) bearing mice through intravenous injection. Comprehensive blood
      tests and careful histological examinations reveal no apparent toxicity of AuNCs
      A@PAA/CaP NPs. Our work highlights the great promise of AuNCs-A@PAA/CaP NPs for
      guiding and monitoring the chemotherapeutic process using simultaneous dual
      modality CT and fluorescence imaging through a single theranostic agent. 

PMID- 25755106
TI  - Familial periventricular nodular heterotopia, epilepsy and Melnick-Needles
      Syndrome caused by a single FLNA mutation with combined gain-of-function and loss
      of-function effects.
AB  - BACKGROUND: Loss-of-function mutations of the FLNA gene cause a neuronal
      migration disorder defined as X-linked periventricular nodular heterotopia (PNH);
      gain-of-function mutations are associated with a group of X-linked skeletal
      dysplasias designed as otopalatodigital (OPD) spectrum. We describe a family in
      which a woman and her three daughters exhibited a complex phenotype combining
      PNH, epilepsy and Melnick-Needles syndrome (MNS), a skeletal disorder assigned to
      the OPD spectrum. All four individuals harboured a novel non-conservative
      missense mutation in FLNA exon 3. METHODS: In all affected family members, we
      performed mutation analysis of the FLNA gene, RT-PCR, ultradeep sequencing
      analysis in FLNA cDNAs and western blot in lymphocyte cells to further
      characterise the mutation. We also assessed the effects on RT-PCR products of
      treatment of patients' lymphocytes with cycloheximide, a nonsense mediated mRNA
      decay (NMD) inhibitor. RESULTS: We identified a novel c.622G>C change in FLNA
      exon 3, leading to the substitution of a highly conserved aminoacid
      (p.Gly208Arg). Gel electrophoresis and ultradeep sequencing revealed the missense
      mutation as well as retention of intron 3. Cycloheximide treatment demonstrated
      that the aberrant mRNA transcript-retaining intron 3 is subjected to NMD. Western
      blot analysis confirmed reduced FLNA levels in lymphocyte cells. CONCLUSIONS: The
      novel c.622G>C substitution leads to two aberrant FLNA transcripts, one of which
      carries the missense mutation, plus a longer transcript resulting from intron 3
      retention. We propose that the exceptional co-occurrence of PNH and MNS, two
      otherwise mutually exclusive allelic phenotypes, is the consequence of a single
      mutational event resulting in co-occurring gain-of-function and loss-of-function
      effects.

PMID- 25755107
TI  - Recent developments in the prevention of chemotherapy-induced nausea and vomiting
      (CINV): a comprehensive review.
AB  - The prevention of chemotherapy-induced nausea and vomiting (CINV) has been
      revolutionized over the past 25 years. Guideline-based treatment means that
      vomiting can be prevented in the majority, but not in all patients. Therefore,
      antiemetic research continues with the goal of optimizing CINV control for all
      patients. This comprehensive review summarizes the research efforts in this field
      over the past few years. Emerging from this research are two new antiemetic
      agents, netupitant/palonosetron, the first antiemetic combination agent and
      rolapitant, a new NK1RA. In addition, studies have evaluated the benefits of
      olanzapine and ginger, explored optimal combinations of agents for delayed CINV
      prevention, confirmed that dexamethasone-sparing regimens are effective, and
      demonstrated the value of NK1RAs in high-dose chemotherapy settings as well as
      with certain moderately emetogenic chemotherapies such as carboplatin. Research
      has also validated the correlation between antiemetic guideline adherence and
      improved CINV control. Finally, regulatory authorities have utilized extreme
      caution in retiring some 5-HT3RAs or decreasing their maximum dose. 

PMID- 25755109
TI  - Right hepatic artery forming caterpillar hump, perforating Calot's triangle into
      the cystic plate and associated with a variant branching pattern of the parent
      vessel.

PMID- 25755108
TI  - The impact of docetaxel-related toxicities on health-related quality of life in
      patients with metastatic cancer (QoliTax).
AB  - BACKGROUND: Docetaxel is a widely used cytotoxic agent. This study evaluates the
      impact of docetaxel toxicities on patient's health-related quality of life (QoL).
      PATIENTS AND METHODS: We conducted a multicenter, prospective, non-interventional
      trial, in which the QoL was assessed using the EORTC QLQ-C30 questionnaires at
      baseline and every 4 weeks up to 40 weeks in patients receiving a docetaxel-based
      chemotherapy for metastatic disease. Treatment-related adverse events were
      correlated with the corresponding QoL scores. Uni- and multivariate analyses were
      applied. RESULTS: From January 2008 to June 2011, a total of 2659 patients were
      included. The majority of patients (48.1%) had prostate cancer, followed by
      breast (17.1%) and non-small-cell-lung cancer (15.8%). Patients received a median
      of 5 docetaxel cycles with the median dose of 75 mg/m(2). The presence of grade
      3/4 diarrhea showed the strongest effect on global health status/QoL average
      scores (50.91 versus 33.06), followed by vomiting (50.91 versus 35.17), dyspnea
      (50.94 versus 35.81), mucositis/stomatitis (50.88 versus 36.41), nausea (50.91
      versus 36.68), infection (50.90 versus 37.14), fatigue (50.90 versus 43.82) and
      anemia (50.91 versus 41.03), P < 0.05 for all comparisons. Grade 3/4
      leukopenia/neutropenia, alopecia, constipation, neurotoxicity and nail disorders
      had no significant impact on the global health status/QoL or other items.
      CONCLUSION: In this large non-interventional trial, docetaxel-associated grade 3
      or 4 toxicities were shown to have a strong detrimental effect on patient's QoL.
      Notably, diarrhea and vomiting had the strongest negative impact on QoL measures.
      This has to be kept in mind while making therapeutic decisions and providing
      optimized supportive treatment measures. CLINICAL TRIALS NUMBER: This study was
      registered at Deutsches Krebsstudienregister (DKSR, primary registry in the WHO
      Registry Network) with the ID 527.

PMID- 25755110
TI  - Melatonin reduces oxidative stress and restores mitochondrial function in the
      liver of rats exposed to chemotherapeutics.
AB  - This study was undertaken to investigate whether administration of melatonin
      protects PVB-Induced oxidative and metabolic toxicity in the liver of Wistar
      rats. Adult male Wistar rats were intraperitoneally injected with either
      melatonin or PVB (cisplatin, vinblastine, and bleomycin) alone or combination for
      a period of 9 weeks. A significant increase in lipid peroxidation levels and
      decrease in catalase and superoxide dismutase activity levels were observed in
      the liver mitochondria of rats treated with PVB indicating increased oxidative
      stress. PVB treatment significantly decreased the succinate dehydrogenase
      activity with a significant increase in lactate dehydrogenase, glucose-6
      phosphate dehydrogenase, aspartate aminotransaminase, alanine aminotransaminase,
      and glutamate dehydrogenase activities indicating deranged hepatic metabolism.
      Melatonin administration, on the other hand was found to significantly improve
      PVB-Induced biochemical changes, bringing them closer to the controls. The
      results from the study provide evidence that treatment with PVB affects hepatic
      metabolism in rats by inducing oxidative stress followed by decreasing
      mitochondrial oxidation and also point towards the clinical potential of
      melatonin as an adjuvant therapy to conventional chemotherapeutic regimens.

PMID- 25755111
TI  - Three-color confocal Forster (or fluorescence) resonance energy transfer
      microscopy: Quantitative analysis of protein interactions in the nucleation of
      actin filaments in live cells.
AB  - Experiments using live cell 3-color Forster (or fluorescence) resonance energy
      transfer (FRET) microscopy and corresponding in vitro biochemical reconstitution
      of the same proteins were conducted to evaluate actin filament nucleation. A
      novel application of 3-color FRET data is demonstrated, extending the analysis
      beyond the customary energy-transfer efficiency (E%) calculations. MDCK cells
      were transfected for coexpression of Teal-N-WASP/Venus-IQGAP1/mRFP1-Rac1, Teal-N
      WASP/Venus-IQGAP1/mRFP1-Cdc42, CFP-Rac1/Venus-IQGAP1/mCherry-actin, or CFP
      Cdc42/Venus-IQGAP1/mCherry-actin, and with single-label equivalents for spectral
      bleedthrough correction. Using confirmed E% as an entry point, fluorescence
      levels and related ratios were correlated at discrete accumulating levels at cell
      peripheries. Rising ratios of CFP-Rac1:Venus-IQGAP1 were correlated with lower
      overall actin fluorescence, whereas the CFP-Cdc42:Venus-IQGAP1 ratio correlated
      with increased actin fluorescence at low ratios, but was neutral at higher
      ratios. The new FRET analyses also indicated that rising levels of mRFP1-Cdc42 or
      mRFP1-Rac1, respectively, promoted or suppressed the association of Teal-N-WASP
      with Venus-IQGAP1. These 3-color FRET assays further support our in vitro results
      about the role of IQGAP1, Rac1, and Cdc42 in actin nucleation, and the
      differential impact of Rac1 and Cdc42 on the association of N-WASP with IQGAP1.
      In addition, this study emphasizes the power of 3-color FRET as a systems biology
      strategy for simultaneous evaluation of multiple interacting proteins in
      individual live cells.

PMID- 25755112
TI  - Sperm global DNA methylation level: association with semen parameters and genome
      integrity.
AB  - Sperm DNA methylation abnormalities have been detected in oligozoospermic men.
      However, the association between sperm DNA methylation defects, sperm parameters
      and sperm DNA, and chromatin integrity remains poorly understood. This study was
      designed to clarify this issue. We recruited a cohort of 92 men (62
      normozoospermic and 30 oligoasthenozoospermic) presenting for infertility
      evaluation during a 1-year period. Sperm global DNA methylation was evaluated by
      an ELISA-like method, DNA fragmentation was evaluated by flow cytometry-based
      terminal transferase dUTP nick end-labeling (TUNEL) assay (reported as DNA
      fragmentation index or DFI), and sperm denaturation was evaluated by aniline blue
      staining (reported as sperm denaturation index or SDI, a marker of chromatin
      compaction). We found a significant positive association between sperm global DNA
      methylation level and conventional sperm parameters (sperm concentration and
      motility), supported by the results of methylation analysis on H19-DMR. We also
      identified significant inverse relationships between sperm global DNA
      methylation, and, both DFI and SDI. However, sperm global DNA methylation level
      was not related to sperm vitality or morphology. Our findings suggest that global
      sperm DNA methylation levels are related to conventional sperm parameters, as
      well as, sperm chromatin and DNA integrity.

PMID- 25755113
TI  - Efficient, Absorption-Powered Artificial Muscles Based on Carbon Nanotube Hybrid
      Yarns.
AB  - A new type of absorption-powered artificial muscle provides high performance
      without needing a temperature change. These muscles, comprising coiled carbon
      nanotube fibers infiltrated with silicone rubber, can contract up to 50% to
      generate up to 1.2 kJ kg(-1) . The drive mechanism for actuation is the rubber
      swelling during exposure to a nonpolar solvent. Theoretical energy efficiency
      conversion can be as high as 16%. 

PMID- 25755114
TI  - ' 'tis bitter cold and I am sick at heart': establishing the relationship between
      outdoor temperature, blood pressure, and cardiovascular mortality.

PMID- 25755116
TI  - Portal vein reconstruction in adult living donor liver transplantation for
      patients with portal vein thrombosis in single center experience.
AB  - BACKGROUND: Liver transplantation (LT) used to be contraindicated in patients
      with portal vein thrombosis (PVT). In comparison to deceased donor LT, living
      donor LT (LDLT) still presents additional difficulties in determining appropriate
      vein grafts and overcoming small-for-size syndrome. Here, we introduce our LDLT
      strategies and assess their outcomes in adult patients with pre-existing PVT.
      METHODS: We performed 282 consecutive adult LDLTs between April 2006 and December
      2011. Forty-eight patients (17%) had pre-existing PVT (grade I; 15, II; 20, III;
      12, IV; 1). RESULTS: Our preferred treatments for PVT were
      thrombectomies/thromboendovenectomies in 30 patients, replaced grafts in seven,
      jump grafts in seven, renoportal anastomosis in one and no surgical intervention
      owing to minimal thrombosis in three. Post-transplant portal vein complications
      occurred in eight of 48 (17%) cases, which were treated by surgery,
      anticoagulation therapy, and/or interventional radiology. Post-transplant
      survival rates of patients with preexisting PVT at 1 year and 5 years were
      comparable to a PVT-free cohort (1 year; 81% vs. 77%, 5 years; 81% vs. 73%).
      CONCLUSIONS: The excellent survival rates in patients with PVT who underwent LDLT
      could be attributed to our strategies, which included surgical techniques and
      timely treatment of postoperative complications.

PMID- 25755117
TI  - MUMAB: A Conversation With the Past.
AB  - In May of 1994, Drs. Bob Brier and Ronn Wade produced the first modern mummy
      embalmed in the ancient Egyptian tradition. MUMAB (Mummy, University of Maryland
      At Baltimore) has been studied over the intervening 18 years as part of the Mummy
      Replication Project, including high-resolution computed tomography scanning,
      magnetic resonance imaging, and histological examination. The radiological study
      of MUMAB is combined here with the firsthand discussion of the processes that
      resulted in the mummy's radiographic appearance. This allows for a close
      examination of the assumptions made in the radiological study of ancient Egyptian
      mummified human remains in a way not possible for the ancient remains themselves.

PMID- 25755115
TI  - TLR2 and neutrophils potentiate endothelial stress, apoptosis and detachment:
      implications for superficial erosion.
AB  - AIMS: Superficial erosion of atheromata causes many acute coronary syndromes, but
      arises from unknown mechanisms. This study tested the hypothesis that Toll-like
      receptor-2 (TLR2) activation contributes to endothelial apoptosis and denudation
      and thus contributes to the pathogenesis of superficial erosion. METHODS AND
      RESULTS: Toll-like receptor-2 and neutrophils localized at sites of superficially
      eroded human plaques. In vitro, TLR2 ligands (including hyaluronan, a matrix
      macromolecule abundant in eroded lesions) induced endothelial stress,
      characterized by reactive oxygen species production, endoplasmic reticulum (ER)
      stress, and apoptosis. Co-incubation of neutrophils with endothelial cells (ECs)
      potentiated these effects and induced EC apoptosis and detachment. We then
      categorized human atherosclerotic plaques (n = 56) based on morphologic features
      associated with superficial erosion, 'stable' fibrotic, or 'vulnerable' lesions.
      Morphometric analyses of the human atheromata localized neutrophils and
      neutrophil extracellular traps (NETs) near clusters of apoptotic ECs in smooth
      muscle cell (SMC)-rich plaques. The number of luminal apoptotic ECs correlated
      with neutrophil accumulation, amount of NETs, and TLR2 staining in SMC-rich
      plaques, but not in 'vulnerable' atheromata. CONCLUSION: These in vitro
      observations and analyses of human plaques indicate that TLR2 stimulation
      followed by neutrophil participation may render smooth muscle cell-rich plaques
      susceptible to superficial erosion and thrombotic complications by inducing ER
      stress, apoptosis, and favouring detachment of EC.

PMID- 25755118
TI  - Computational prediction of manually gated rare cells in flow cytometry data.
AB  - Rare cell identification is an interesting and challenging question in flow
      cytometry data analysis. In the literature, manual gating is a popular approach
      to distill flow cytometry data and drill down to the rare cells of interest,
      based on prior knowledge of measured protein markers and visual inspection of the
      data. Several computational algorithms have been proposed for rare cell
      identification. To compare existing algorithms and promote new developments,
      FlowCAP-III put forward one computational challenge that focused on this
      question. The challenge provided flow cytometry data for 202 training samples and
      two manually gated rare cell types for each training sample, roughly 0.02 and
      0.04% of the cells, respectively. In addition, flow cytometry data for 203
      testing samples were provided, and participants were invited to computationally
      identify the rare cells in the testing samples. Accuracy of the identification
      results was evaluated by comparing to manual gating of the testing samples. We
      participated in the challenge, and developed a method that combined the Hellinger
      divergence, a downsampling trick and the ensemble SVM. Our method achieved the
      highest accuracy in the challenge.

PMID- 25755119
TI  - Dose-dependent effects of homologous seminal plasma on motility and kinematic
      characteristics of post-thaw stallion epididymal spermatozoa.
AB  - Preservation of epididymal spermatozoa is important to save genetic material of
      endangered species and breeds, or in case of unexpected injury, which will end
      the breeding career of valuable sires. Seminal plasma (SP) influences sperm
      quality in a dose-dependent manner and its addition to preserved semen
      immediately before insemination may be beneficial for sperm fertility. Increased
      plasma membrane stability of epididymal spermatozoa reduces freezing injury of
      cells, and the addition of SP after freezing and thawing might have activating
      and protecting effects on spermatozoa within the female genital tract. In this
      study, epididymal spermatozoa were harvested by retrograde flush of the
      epididymal cauda immediately after routine castration and frozen. Seminal plasma
      was collected from other six stallions. Homologous SP (SP from the same species,
      but from a different animal) was added to frozen-thawed epididymal spermatozoa at
      concentrations of 0, 5, 20, 50 and 80% SP. Addition of SP increased sperm
      motility and influenced kinematic values in a dose-dependent manner (p < 0.05).
      Motility improved at concentrations of 20 and 50% SP, but did not further
      increase at 80% SP. There was no difference in sperm motility among SP from six
      different donor stallions regardless of the concentrations of SP (p > 0.05).
      Total and progressive motility of ten frozen-thawed epididymal spermatozoa
      samples collected from different stallions after dilution with extender and 5,
      20, 50 or 80% SP differed significantly (p < 0.05). In conclusion, addition of
      homologous SP to frozen-thawed stallion epididymal spermatozoa immediately
      improved motility in a dose-dependent manner regardless of semen quality of SP
      donor stallions. This might positively influence fertility when SP is added
      before insemination. Moreover, there seems to be a threshold level of SP
      concentration for optimal improvement of sperm motility.

PMID- 25755120
TI  - Purification and simultaneous immobilization of Arabidopsis thaliana
      hydroxynitrile lyase using a family 2 carbohydrate-binding module.
AB  - Tedious, time- and labor-intensive protein purification and immobilization
      procedures still represent a major bottleneck limiting the widespread application
      of enzymes in synthetic chemistry and industry. We here exemplify a simple
      strategy for the direct site-specific immobilization of proteins from crude cell
      extracts by fusion of a family 2 carbohydrate-binding module (CBM) derived from
      the exoglucanase/xylanase Cex from Cellulomonas fimi to a target enzyme. By
      employing a tripartite fusion protein consisting of the CBM, a flavin-based
      fluorescent protein (FbFP), and the Arabidopsis thaliana hydroxynitrile lyase
      (AtHNL), binding to cellulosic carrier materials can easily be monitored via FbFP
      fluorescence. Adsorption properties (kinetics and quantities) were studied for
      commercially available Avicel PH-101 and regenerated amorphous cellulose (RAC)
      derived from Avicel. The resulting immobilizates showed similar activities as the
      wild-type enzyme but displayed increased stability in the weakly acidic pH range.
      Finally, Avicel, RAC and cellulose acetate (CA) preparations were used for the
      synthesis of (R)-mandelonitrile in micro-aqueous methyl tert-butyl ether (MTBE)
      demonstrating the applicability and stability of the immobilizates for
      biotransformations in both aqueous and organic reaction systems. 

PMID- 25755121
TI  - Expanding perspective on music therapy for symptom management in cancer care.
AB  - BACKGROUND: Symptom management is a frequently researched treatment topic in
      music therapy and cancer care. Representations in the literature of music
      interventions for symptom management, however, have often overlooked the human
      experiences shaping those symptoms. This may result in music therapy being
      perceived as a linear intervention process that does not take into account
      underlying experiences that contribute to symptom experiences. OBJECTIVE: This
      study explored patient experiences underlying symptoms and symptom management in
      cancer care, and examined the role of music therapy in that clinical process.
      METHODS: This study analyzed semi-structured, open-ended exit interviews obtained
      from 30 participants during a randomized controlled trial investigating the
      differential impact of music therapy versus music medicine interventions on
      symptom management in participants with cancer. Interviews were conducted by a
      research assistant not involved with the clinical interventions. Exit interview
      transcripts for 30 participants were analyzed using an inductive, latent,
      constructivist method of thematic analysis. RESULTS: Three themes-Relaxation,
      Therapeutic relationship, and Intrapersonal relating-capture elements of the
      music therapy process that (a) modified participants' experiences of adjustments
      in their symptoms and (b) highlighted the depth of human experience shaping their
      symptoms. These underlying human experiences naturally emerged in the therapeutic
      setting, requiring the music therapist's clinical expertise for appropriate
      support. CONCLUSIONS: Symptom management extends beyond fluctuation in levels and
      intensity of a surface-level symptom to incorporate deeper lived experiences. The
      authors provide recommendations for clinical work, entry-level training as
      related to symptom management, implications for evidence-based practice in music
      therapy, and methodology for future mixed methods research.

PMID- 25755122
TI  - Response to Randell et al. "Using realist reviews to understand how health IT
      works, for whom, and in what circumstances".

PMID- 25755123
TI  - Using realist reviews to understand how health IT works, for whom, and in what
      circumstances.

PMID- 25755124
TI  - Electronic health records and health care quality over time in a federally
      qualified health center.
AB  - The longitudinal effects of electronic health records (EHRs) on ambulatory
      quality are not clear. It is not known whether adoption and meaningful use of
      EHRs result in a brief period of quality improvement that then plateaus, or
      whether with ongoing use quality improvement continues. We studied health care
      quality at six sites of a Federally Qualified Health Center in New York State
      over 3 years (2008-2010) for 25 290 unique patients. Patients were twice as
      likely to receive recommended care on a set of 12 quality measures (11 of which
      are included in Stage 1 Meaningful Use) 3 years post-EHR implementation, compared
      to 1-year post-implementation (odds ratio 1.97; 95% confidence interval, 1.91
      2.03). The magnitude of absolute improvement ranged from 5% to 20% per measure.
      EHRs were associated with continuing improvement in health care quality for at
      least 3 years post-implementation in the safety-net setting of a Federally
      Qualified Health Center. 

PMID- 25755125
TI  - Careful experiments advance the science of informatics.

PMID- 25755126
TI  - Impact of the meaningful use incentive program on electronic health record
      adoption by US children's hospitals.
AB  - OBJECTIVE: We determined adoption rates of pediatric-oriented electronic health
      record (EHR) features by US children's hospitals and assessed perceptions
      regarding the suitability of commercial EHRs for pediatric care and the influence
      of the meaningful use incentive program on implementation of pediatric-oriented
      features. MATERIALS AND METHODS: We surveyed members of the Children's Hospital
      Association. We measured adoption of 19 pediatric-oriented features and asked
      whether commercial EHRs include key pediatric-focused capabilities. We inquired
      about the meaningful use program's relevance to pediatrics and its influence on
      EHR implementation priorities. RESULTS: Of 164 general acute care children's
      hospitals, 100 (61%) responded to the survey. Rates of comprehensive (across all
      pediatric units) adoption ranged from 37% (age-, gender-, and weight-adjusted
      blood pressure percentiles and immunization contraindication warnings) to 87%
      (age in appropriate units). Implementation rates for several features varied
      significantly by children's hospital type. Nearly 60% of hospitals reported
      having EHRs that do not contain all features essential for high-quality care. A
      majority of hospitals indicated that the meaningful use program has had no effect
      on their adoption of pediatric features, while 26% said they have delayed or
      forgone incorporation of such features because of the program. CONCLUSIONS:
      Children's hospitals are implementing pediatric-focused features, but a sizable
      proportion still finds their systems suboptimal for pediatric care. The
      meaningful use incentive program is failing to promote and in some cases delaying
      uptake of pediatric-oriented features.

PMID- 25755127
TI  - Pharmacovigilance from social media: mining adverse drug reaction mentions using
      sequence labeling with word embedding cluster features.
AB  - OBJECTIVE: Social media is becoming increasingly popular as a platform for
      sharing personal health-related information. This information can be utilized for
      public health monitoring tasks, particularly for pharmacovigilance, via the use
      of natural language processing (NLP) techniques. However, the language in social
      media is highly informal, and user-expressed medical concepts are often
      nontechnical, descriptive, and challenging to extract. There has been limited
      progress in addressing these challenges, and thus far, advanced machine learning
      based NLP techniques have been underutilized. Our objective is to design a
      machine learning-based approach to extract mentions of adverse drug reactions
      (ADRs) from highly informal text in social media. METHODS: We introduce ADRMine,
      a machine learning-based concept extraction system that uses conditional random
      fields (CRFs). ADRMine utilizes a variety of features, including a novel feature
      for modeling words' semantic similarities. The similarities are modeled by
      clustering words based on unsupervised, pretrained word representation vectors
      (embeddings) generated from unlabeled user posts in social media using a deep
      learning technique. RESULTS: ADRMine outperforms several strong baseline systems
      in the ADR extraction task by achieving an F-measure of 0.82. Feature analysis
      demonstrates that the proposed word cluster features significantly improve
      extraction performance. CONCLUSION: It is possible to extract complex medical
      concepts, with relatively high performance, from informal, user-generated
      content. Our approach is particularly scalable, suitable for social media mining,
      as it relies on large volumes of unlabeled data, thus diminishing the need for
      large, annotated training data sets.

PMID- 25755128
TI  - Preoperative intramuscular adipose tissue content is a novel prognostic predictor
      after hepatectomy for hepatocellular carcinoma.
AB  - BACKGROUND: Sarcopenia has been shown to be an independent predictor of lower
      disease-free and overall survival in various kinds of diseases. The quality of
      skeletal muscle has recently attracted much attention as a new parameter of
      sarcopenia. METHODS: We performed a retrospective analysis of 477 patients
      undergoing hepatectomy for hepatocellular carcinoma (HCC) between April 2005 and
      August 2014. The quality of skeletal muscle was evaluated by intramuscular
      adipose tissue content (IMAC) using preoperative computed tomography (CT)
      imaging. The impact of IMAC on outcomes after hepatectomy for HCC was analyzed.
      RESULTS: Patients with high IMAC showed older age, higher body mass index, higher
      indocyanine green retention test at 15 min, and more operative blood loss. The
      overall and recurrence-free survival rates were significantly lower in patients
      with high IMAC than in patients with normal IMAC (P < 0.0001, P = 0.0012,
      respectively). Multivariate analysis showed that high IMAC was the significant
      risk factor for death (hazard ratio [HR] = 2.942; P < 0.0001) and for HCC
      recurrence (HR = 1.529; P = 0.0007) after hepatectomy. CONCLUSIONS: Preoperative
      quality of skeletal muscle was closely correlated with postoperative mortality
      and HCC recurrence. IMAC could be incorporated into new selection criteria for
      hepatectomy for HCC.

PMID- 25755129
TI  - Technical Limitations on the Use of Traditional Magnetic Resonance Imaging in the
      Evaluation of Mummified Remains: A View From a Hands-On Radiologic Technologist's
      Perspective.
AB  - Noninvasive imaging tools have been the standard in mummy studies for several
      decades focusing primarily on CT scan technology. Although magnetic resonance
      imaging (MRI) has been attempted on mummified tissues on numerous occasions these
      have met with varying degrees of success. The basic physics of MRI are reviewed
      here with an emphasis on how the physics limit the success of MRI in mummified
      tissues. Adjusting MRI parameters can enhance the images produced with a summary
      table that considers the effect of adjustments within these parameters. Several
      mummies with varying methods of preservation have been included in this study and
      MRI images presented and the results are critically assessed. MRI can generate
      basic images in most tissues even when significantly desiccated. Using an
      understanding of the essentials of MRI physics, with the adjustment of MRI
      parameters, the data acquisition process can be enhanced to create the best
      possible images. When successfully applied, MRI generated images can allow for
      the resolution of soft tissue differences, especially of collapsed internal organ
      masses, even in dehydrated mummies that are much less effectively rendered in CT
      scans.

PMID- 25755130
TI  - Facilitated gate setting by sequential dot plot scanning.
AB  - Microbial communities comprising thousands of unknown organisms can be studied
      flow cytometrically by applying just one fluorescent parameter and using scatter
      characteristics of cells. Resulting 2D-plots need to represent high numbers of
      cells to detect the many subcommunities, even rare ones that might be present in
      the sample. Evaluation of such data can be faulty and subjective due to the low
      number of parameters available for data discrimination and the high numbers of
      overlaying events. Here, we describe a procedure that helps to evaluate such data
      using facilitated gate setting by sequential dot-plot scanning.

PMID- 25755131
TI  - Comprehensive investigation in patients affected by sperm macrocephaly and
      globozoospermia.
AB  - The aim of this study was to provide a comprehensive genetic/phenotypic
      characterization of subjects suffering infertility owing to sperm macrocephaly (n
      = 3) or globozoospermia (n = 9) and to investigate whether the patients' genetic
      status was correlated with the alteration of various sperm parameters. AURKC was
      sequenced in case of sperm macrocephaly while the DPY19L2 status has been
      analyzed by multiple approaches including a novel qPCR-based copy number assay in
      case of globozoospermia. Globozoospermic patients were also analyzed for SPACA1,
      a novel candidate gene herein tested for the first time in humans. The effect of
      the patients' genetic status was interrogated by implementing the molecular
      screening with the characterization of several sperm parameters: (i) routine
      sperm analysis, integrated with transmission electron microscopy; (ii) sperm
      fluorescent in situ hybridization (FISH) analysis; (iii) sperm DNA fragmentation
      (DF) analysis. Moreover, for the first time, we performed microsatellite
      instability analysis as a marker of genome instability in men with sperm
      macrocephaly and globozoospermia. Finally, artificial reproductive technology
      (ART) history has been reported for those patients who underwent the treatment.
      Macrocephalic patients had an AURKC mutation and >89% tetraploid, highly
      fragmented spermatozoa. DPY19L2 was mutated in all patients with >80%
      globozoospermia: the two homozygous deleted men and the compound heterozygous
      showed the severest phenotype (90-100%). The newly developed qPCR method was
      fully validated and has the potential of detecting also yet undiscovered
      deletions. DPY19L2 status is unlikely related to FISH anomalies and DF, although
      globozoospermic men showed a higher disomy rate and DF compared with internal
      reference values. No patient was mutated for SPACA1. Our data support the general
      agreement on the negative correlation between macro/globozoospermia and
      conventional intracytoplasmic sperm injection outcomes. Microsatellites were
      stable in all patients analyzed. The comprehensive picture provided on these
      severe phenotypes causing infertility is of relevance in the management of
      patients undergoing ART.

PMID- 25755132
TI  - Fluorine in drug design: a case study with fluoroanisoles.
AB  - Anisole and fluoroanisoles display distinct conformational preferences, as
      evident from a survey of their crystal structures. In addition to altering the
      free ligand conformation, various degrees of fluorination have a strong impact on
      physicochemical and pharmacokinetic properties. Analysis of anisole and
      fluoroanisole matched molecular pairs in the Pfizer corporate database reveals
      interesting trends: 1) PhOCF3 increases log D by ~1 log unit over PhOCH3
      compounds; 2) PhOCF3 shows lower passive permeability despite its higher
      lipophilicity; and 3) PhOCF3 does not appreciably improve metabolic stability
      over PhOCH3 . Emerging from the investigation, difluoroanisole (PhOCF2 H) strikes
      a better balance of properties with noticeable advantages of log D and
      transcellular permeability over PhOCF3 . Synthetic assessment illustrates that
      the routes to access difluoroanisoles are often more straightforward than those
      for trifluoroanisoles. Whereas replacing PhOCH3 with PhOCF3 is a common tactic to
      optimize ADME properties, our analysis suggests PhOCF2 H may be a more attractive
      alternative, and greater exploitation of this motif is recommended.

PMID- 25755133
TI  - Expression of Periostin in Normal, Atopic, and Nonatopic Chronically Inflamed
      Canine Skin.
AB  - In humans, periostin plays a critical role in the enhancement and chronicity of
      allergic skin inflammation; however, whether it is involved in the pathogenesis
      of canine dermatitis remains unknown. The aim of this study was to examine the
      expression patterns of periostin in healthy, atopic, and nonatopic chronically
      inflamed canine skin. Biopsy specimens from 47 dogs with skin disease and normal
      skin tissue from 5 adult beagles were examined by light microscopy,
      immunohistochemistry, and in situ hybridization. In normal skin, periostin was
      localized just beneath the epidermis and around the hair follicles. In
      chronically inflamed skin, periostin expression was most intense in the dermis
      with inflammatory cell infiltrates. In contrast, low levels of periostin were
      detected in acutely inflamed and noninflamed skin. Conversely, all canine atopic
      dermatitis tissues characteristically showed the most intense expression of
      periostin in the superficial dermis, particularly at the epidermal-dermal
      junction. In situ hybridization showed that periostin mRNA was broadly expressed
      in the basal epidermal keratinocytes, outer root sheath cells, and dermal
      fibroblasts in normal dog skin. High expression of periostin mRNA was observed in
      fibroblasts in dog skin with chronically inflamed dermatitis. Moreover, in some
      chronically inflamed skin specimens, periostin mRNA expression was increased in
      basal keratinocytes. The severity score of chronic pathologic changes and CD3+
      cell number in the dermis were correlated with distribution pattern of periostin
      in the atopic skin. These data suggest that periostin could play a role in the
      pathophysiology of chronic dermatitis, including atopic dermatitis, in dogs. 

PMID- 25755134
TI  - Different Growth Patterns of Canine Prostatic Carcinoma Suggests Different Models
      of Tumor-Initiating Cells.
AB  - Controversies remain regarding the cell type from which human prostate cancer
      originates, and many attempts have been made to identify the cellular origin of
      canine prostate cancer but without definitive proof. This study aims to evaluate
      the expression of luminal (androgen receptor [AR], cytokeratin [CK]8/18) and
      basal (CK14, CK5) cell markers in different histologic subtypes of canine
      prostatic carcinoma (PC) and to suggest the most likely tumor-initiating cells.
      Normal prostates (n = 8) were characterized by AR+CK8/18+ luminal cells and few
      CK5+ basal cells, while CK14 was absent. Similar pattern was observed in all 35
      prostates with benign prostatic hyperplasia, except few scattered CK14+ basal
      cells in 13 samples (37.14%). AR was localized in the nucleus of both normal and
      hyperplastic cells. In 34 samples of PC, the following growth patterns were
      identified: cribriform (44.12%), solid (32.35%), small acinar/ductal (20.59%),
      and micropapillary (2.94%). Most PCs expressed AR and CK8/18, while CK5 and CK14
      expression was observed in 25% and 20% of cases, respectively. AR revealed a
      variable intracellular distribution, both nuclear and cytoplasmic. Solid PC was
      characterized by an undifferentiated or aberrant phenotype with a reduced
      expression of AR and CK8/18, increased number of CK14+ cells, and 7 antigen
      expression patterns. This study demonstrated a predominance of differentiated
      luminal cell types in canine prostatic tumors, although the role of basal cells
      in prostate carcinogenesis should also be considered. Moreover, few scattered
      CK5+ cells in AR+CK8/18+ tumors identified the existence of intermediate cells,
      from which neoplastic transformation may alternatively commence. 

PMID- 25755136
TI  - In vitro analysis of overall particulate contamination exposure during multidrug
      IV therapy: impact of infusion sets.
AB  - BACKGROUND: Drug incompatibilities, recognizable through precipitate, may have
      clinical consequences for patients, especially during multidrug IV therapies,
      where vancomycin and piperacillin are present. Drug concentration and infusion
      set influence the overall particulate contamination of pediatric infusion
      protocols. The use of multi-lumen infusion sets could prevent such
      incompatibilities. Our goal was to define and assess a new way to infuse these
      drugs during leukemia treatment in children. PROCEDURES: This in vitro study
      focused on a pediatric multidrug protocol for patients diagnosed with
      lymphoblastic leukemia and receiving allogeneic transplantation. Different
      vancomycin concentrations were tested to infuse incompatible drugs simultaneously
      without any particle formation (optimized multidrug protocol). A dynamic particle
      count test was used over 24 hr to evaluate the overall particulate contamination
      of our standard and optimized multidrug protocols, using both a standard and a
      multi-lumen infusion set. RESULTS: No visible particles were detected on a
      decreased vancomycin concentration compared to the standard dose. For the
      optimized multidrug protocol, the use of a multi-lumen infusion set reduced
      overall particulate contamination by 68%, compared to the standard infusion set
      (P = 0.002). Large-sized particles were significantly reduced when using the
      multi-lumen infusion set approximately 60% (P = 0.027) and 90% (P = 0.009) for
      particle sizes >=10 MUm and 25 MUm, respectively. CONCLUSIONS: This study
      demonstrates that a large number of particles can be administered during
      parenteral multidrug infusion. The choice of drug concentration and/or the type
      of infusion set may reduce this. Further studies are required to evaluate adverse
      clinical effects.

PMID- 25755135
TI  - The relationship between acculturation and infant feeding styles in a Latino
      population.
AB  - OBJECTIVE: To assess the relationship between parental acculturation and infant
      feeding style in a sample of Latino parents. METHODS: A post hoc analysis was
      performed using data from an ongoing four-site randomized controlled trial to
      promote early childhood obesity prevention. Cross-sectional data of parent-child
      dyads at the 12-month well-child visit who self-reported their Latino ethnicity
      were analyzed. The Short Acculturation Scale for Hispanics (SASH) and a subset of
      the Infant Feeding Style Questionnaire (IFSQ) that assessed four primary feeding
      styles were administered. SASH level (low vs. high) with each feeding style was
      compared by analyses. RESULTS: Complete SASH data were available for 398 of 431
      Latino dyads. Median SASH score was 1.8 (IQR 1.4-2.7); 82% of participants had
      low acculturation (score < 3). Of the nine outcome variables, four were
      significantly associated with SASH: "Laissez-Faire/attention" (AOR: 2.3; 95% CI:
      1.06-5.13; P = 0.004), "Laissez-Faire/diet quality" (AOR: 3.9; 95% CI: 1.7-8.75;
      P = 0.005), "Pressuring as soothing" (AOR: 3.6; 95% CI:1.63-8.05; P = 0.007), and
      "Restrictive/diet quality" (AOR: 0.4; 95% CI: 0.19-0.94; P = 0.031). CONCLUSIONS:
      Latino parents with lower acculturation were more likely than those with higher
      acculturation to endorse feeding styles that are associated with child obesity.
      Further research is needed to determine why acculturation and feeding style
      relate.

PMID- 25755137
TI  - Congenital bilateral absence of the vas deferens: the impact of spermatogenesis
      quality on intracytoplasmic sperm injection outcomes in 108 men.
AB  - In azoospermic men with congenital bilateral absence of the vas deferens (CBAVD),
      it is not known whether the outcomes of intracytoplasmic sperm injection (ICSI)
      depend on the quality of testicular spermatogenesis (as determined
      histopathologically). We retrospectively studied the impact of spermatogenesis
      quality on ICSI outcomes in 108 azoospermic men with CBAVD consulting in a
      university hospital's department of andrology and reproductive biology. As part
      of an ICSI program, sperm samples were obtained from the epididymis [by
      microsurgical epididymal sperm aspiration (MESA); n = 47] or the testis [by
      testicular sperm extraction (TESE); n = 14] or both (MESA + TESE, n = 47). In the
      TESE group (i.e., TESE-only and MESA + TESE), spermatogenesis was normal in 21 of
      the 108 men (19.4%) and hypospermatogenesis occurred in 33 (30.5%). The
      fertilization rate was significantly lower in the hypospermatogenic group than in
      the normospermatogenesis group (65.6 and 72.9%, respectively; p = 0.02); this was
      also true for the embryo cleavage rate (88.6 and 92.1%, respectively; p = 0.007),
      and the proportion of embryos with fewer than 30% of enucleate fragments (79.5
      and 86.9%, respectively; p = 0.02). Our study results showed that impaired
      spermatogenesis had a negative impact on certain early-stage biological outcomes
      of ICSI. In CBAVD, male factors are likely to exert a harmful effect on the early
      stages of embryo development.

PMID- 25755138
TI  - Development of a molecularly imprinted solid-phase extraction sorbent for the
      selective extraction of telmisartan from human urine.
AB  - A novel molecularly imprinted solid-phase extraction with spectrofluorimetry
      method has been developed for the selective extraction of telmisartan from human
      urine. Molecularly imprinted polymers were prepared by a noncovalent imprinting
      approach through UV-radical polymerization using telmisartan as a template
      molecule, 2-dimethylamino ethyl methacrylate as a functional monomer, ethylene
      glycol dimethacrylate as a cross-linker, N,N-azobisisobutyronitrile as an
      initiator, chloroform as a porogen. Molecularly imprinted polymers and
      nonimprinted control polymer sorbents were dry-packed into solid-phase extraction
      cartridges, and eluates from cartridges were analyzed using a spectrofluorimeter.
      Limit of detection and limit of quantitation values were 11.0 and 36.0 ng/mL,
      respectively. A very high imprinting factor (16.1) was achieved and recovery
      values for the telmisartan spiked in human urine were in the range of 76.1-79.1%.
      In addition, relatively low within-day (0.14-1.6%) and between-day (0.11-1.31%)
      precision values were obtained. Valsartan was used to evaluate the selectivity of
      sorbent as well. As a result, a sensitive, selective, and simple molecularly
      imprinted solid-phase extraction with spectrofluorimetry method has been
      developed and successfully applied to the direct determination telmisartan in
      human urine. 

PMID- 25755139
TI  - Increasing synovitis and bone marrow lesions are associated with incident joint
      tenderness in hand osteoarthritis.
AB  - OBJECTIVES: To explore whether changes of MRI-defined synovitis and bone marrow
      lesions (BMLs) are related to changes in joint tenderness in a 5-year
      longitudinal study of the Oslo hand osteoarthritis (OA) cohort. METHODS: We
      included 70 patients (63 women, mean (SD) age 67.9 (5.5) years). BMLs and
      contrast-enhanced synovitis in the distal and proximal interphalangeal joints
      were evaluated on 0-3 scales in n=69 and n=48 patients, respectively. Among
      joints without tenderness at baseline, we explored whether increasing/incident
      synovitis and BMLs were associated with incident joint tenderness using
      generalised estimating equations. Among joints with tenderness at baseline, we
      explored whether decreasing or resolution of synovitis and BMLs were associated
      with loss of joint tenderness. We adjusted for age, sex, body mass index, follow
      up time and changes in radiographic OA. RESULTS: Among joints without tenderness
      at baseline, increasing/incident synovitis and BMLs were seen in 45 of 220
      (20.5%) and 47 of 312 (15.1%) joints, respectively. Statistically significant
      associations to incident joint tenderness were found for increasing/incident
      synovitis (OR=2.66, 95% CI 1.38 to 5.11) and BMLs (OR=2.85, 95% CI 1.23 to 6.58)
      independent of structural progression. We found a trend that resolution of
      synovitis (OR=1.72, 95% CI 0.80 to 3.68) and moderate/large decreases of BMLs
      (OR=1.90, 95% CI 0.57 to 6.33) were associated with loss of joint tenderness, but
      these associations were non-significant. CONCLUSIONS: The Oslo hand OA cohort is
      the first study with longitudinal hand MRIs. Increasing synovitis and BMLs were
      significantly associated with incident joint tenderness, whereas no significant
      associations were found for decreasing or loss of synovitis and BMLs.

PMID- 25755140
TI  - Response to: 'drugs and cardiovascular risk in inflammatory arthritis: another
      case of glucocorticoid-bashing?' by Dr Boers.

PMID- 25755141
TI  - Group IIE secretory phospholipase A2 regulates lipolysis in adipocytes.
AB  - OBJECTIVE: To examine the function of group IIE secretory phospholipase A(2)
      (sPLA(2) -IIE) in adipocytes and to explore the possible signaling mechanism
      involved. METHODS: The expression of sPLA(2) -IIE was demonstrated using real
      time PCR and Western blot analysis. Lipid accumulation was evaluated via the
      measurement of cellular triglycerides (TG). Lipolysis was quantified by measuring
      the release of free glycerol. The expressions of M-type sPLA(2) receptor (PLA(2)
      R1) and the genes encoding adipogenic proteins were measured using real-time PCR.
      The activities of the Janus kinase 2 (JAK2), extracellular regulated protein
      kinase (ERK), and hormone-sensitive lipase (HSL) were determined using Western
      blot. RESULTS: sPLA(2) -IIE(-/-) mice gained significantly more epididymal fat
      than wild-type (WT) mice. When treated with adipogenic stimuli ex vivo, stromal
      vascular cells isolated from the adipose tissue of sPLA(2) -IIE(-/-) mice
      accumulated significantly more TG than those from WT mice. Conversely, a
      significant reduction in lipid accumulation and an increase of free glycerol were
      observed in OP9 cells overexpressing sPLA(2) -IIE and in 3T3-L1 cells treated
      with sPLA(2) -IIE protein. Moreover, sPLA(2) -IIE significantly induced adipocyte
      glycerol release and HSL activity, which was inhibited by PD98059, an ERK
      inhibitor. CONCLUSIONS: sPLA(2) -IIE regulates lipolysis in adipocytes, likely
      through the ERK/HSL signaling pathway.

PMID- 25755142
TI  - Neuroanatomical Phenotypes Are Consistent With Autism-Like Behavioral Phenotypes
      in the 15q11-13 Duplication Mouse Model.
AB  - Paternally and maternally inherited deletions and duplications of human
      chromosome 15q11-13 are relatively common in the human population. Furthermore,
      duplications in the 15q region are often associated with autism. Both maternal
      and paternal interstitial 15q11-13 duplication mouse models have been previously
      created, where several behavioral differences were found in the paternal
      duplication (patDp/+) mouse but not in the maternal duplication (matDp/+). These
      included decreased sociability, behavioral inflexibility, abnormal ultrasonic
      vocalizations, decreased spontaneous activity, and increased anxiety. Similarly,
      in the current study, we found several anatomical differences in the patDp/+ mice
      that were not seen in the matDp/+ mice. Regional differences that are evident
      only in the paternal duplication are a smaller dentate gyrus and smaller medial
      striatum. These differences may be responsible for the behavioral inflexibility.
      Furthermore, a smaller dorsal raphe nucleus could be responsible for the reported
      serotonin defects. This study highlights consistency that can be found between
      behavioral and anatomical phenotyping.

PMID- 25755143
TI  - Wiring for independence: positive feedback motifs facilitate individuation of
      traits in development and evolution.
AB  - Independent selection response of a trait is contingent on the availability of
      genetic variation that is not entangled with other traits. Mechanistically, such
      variational individuation in spite of shared genome results from gene regulation.
      Changes that increase individuation of traits are likely caused by gene
      regulatory changes. Yet the effect of regulatory evolution on population
      variation is understudied. Trait individuation also occurs during development.
      Developmental differentiation involves two stages-induction of differentiation
      and the maintenance of differentiated fate. The corresponding gene regulatory
      transition involves the feed-forward and the regulated feedback motifs. Here we
      consider analogous transition pattern at the evolutionary scale, establishing an
      autonomous regulatory sub-network involved in the independent trait variation. A
      population genetic simulation of regulated feedback loop dynamics under small
      perturbations shows a decoupling of variation in gene expression between the
      upstream gene and the responding downstream gene. We furthermore observe that the
      ranges of dynamics that can be generated by feedback and feed-forward networks
      overlap. Such phenotypic overlap enables genetic accessibility of network
      specific expression dynamics. We suggest that feedback topology may eventually
      confer selective advantage leading from a gradual process to threshold
      individuation, i.e., the emergence of a novel trait.

PMID- 25755144
TI  - Using nonrandomized studies to inform complex clinical decisions: the thorny
      issue of cranial radiation therapy for T-cell acute lymphoblastic leukemia.
AB  - BACKGROUND: There are no randomized controlled trials to inform the decision of
      which cranial radiation therapy (CRT) strategy to apply to pediatric patients
      with T-cell acute lymphoblastic leukemia (ALL). PROCEDURE: We performed a
      decision analysis using a Markov model in which we compared the life expectancy
      and quality-adjusted life expectancy when administering one of three CRT
      strategies to a cohort of patients with T-cell ALL: (1) omission of CRT for all
      patients; (2) CRT only for those with evidence of leukemic involvement in the
      central nervous system at diagnosis (therapeutic strategy); or (3) CRT for all
      (prophylactic strategy). RESULTS: When considering plausible event-free survival
      rates and late mortality after cure for groups of pediatric patients with T-cell
      ALL, the strategies of omitting CRT, administering therapeutic CRT, and
      administering prophylactic CRT result in similar short-term (7-year) survival.
      When considering the increased contribution of deaths from late effects, the
      strategy of prophylactic CRT is associated with lower life expectancy when
      compared to the other two strategies. The Monte Carlo probabilistic sensitivity
      analysis demonstrated that the strategy of prophylactic CRT was the preferred
      strategy only 5% of the time. CONCLUSIONS: Similar short-term survival may be
      expected when comparing the strategies of total omission of CRT, therapeutic CRT,
      and prophylactic CRT for patients with T-cell ALL. Long-term survival is likely
      inferior for the strategy of prophylactic CRT. The synthesis of nonrandomized
      trials and the application of decision analysis can help inform complex decision
      making in pediatric oncology.

PMID- 25755145
TI  - Evidence from enzymatic and meta-analyses does not support a direct association
      between USP26 gene variants and male infertility.
AB  - Do men who carry mutations in USP26 have an increased risk of infertility? The
      association between mutations in USP26 gene and male infertility has been studied
      intensively. However, the results from different groups are controversial. In
      particular, biological function of the mutant proteins remains to be elucidated.
      In this study, we conducted a USP cleavage assay and a meta-analysis of the
      published literature (up to 31 May 2013) to evaluate the impact of five frequent
      mutations (NM_031907.1: c.363_364insACA, c.494T>C, c.1423C>T, c.1090C>T,
      c.1737G>A) on enzymatic activity of the USP26 and to assess the strength of the
      association between those mutations and male infertility. The USP cleavage assay
      showed that those mutations do not affect USP26 enzymatic activity. Moreover, the
      results of meta-analysis of ten case-control studies (in total 1716 patients and
      2597 controls) revealed no significant association (P > 0.05) between USP26
      mutations and male infertility. The pooled ORs were 1.58 (95% CI: 0.81, 3.10) for
      cluster mutations (c.363_364insACA, c.494T>C, c.1423C>T), 1.60 (95% CI: 0.93,
      2.74) for c.1090 C>T and 2.64 (95% CI: 0.97, 7.20) for c.1737 G>A. Evidence from
      both enzymatic and meta-analyses does not support a direct association between
      USP26 variants and male infertility. Further research is necessary to study the
      biological function of USP26, which may provide clues as to the regulation of
      androgen receptor signalling.

PMID- 25755146
TI  - Assembling the pieces of macromolecular complexes: Hybrid structural biology
      approaches.
AB  - Hybrid approaches in structural biology have gained considerable interest for
      uncovering the molecular architectures of large and transient biological systems.
      In particular, MS-based methods and structural electron microscopy can complement
      conventional tools, such as X-ray crystallography and NMR spectroscopy. However,
      bringing together the data derived from diverse sources requires sophisticated
      methods that can efficiently deal with intrinsic ambiguities and heterogeneities
      of the vast amount of data available. Here, we highlight hybrid approaches for
      studying dynamic assemblies, such as transient soluble and integral membrane
      protein complexes. In this review, we emphasize the integration of the wide range
      of emerging MS-based methods, such as ion mobility, native MS, hydrogen-deuterium
      exchange MS and chemical cross-linking MS, with data acquired from cryo electron
      microscopy and X-ray crystallography and further provide a future outlook of
      hybrid structural biology approaches. 

PMID- 25755147
TI  - Beta-diversity metrics of the upper digestive tract microbiome are associated
      with body mass index.
AB  - OBJECTIVE: Studies of the fecal microbiome have implicated the gut microbiota in
      obesity, but few studies have examined the microbial diversity at other sites.
      The association between obesity and the upper gastrointestinal (UGI) microbial
      diversity was explored. METHODS: The UGI microbiome of 659 healthy Chinese adults
      with a measured body mass index (BMI) range of 15.0 to 35.7 was characterized
      using the 16S rRNA gene DNA microarray (HOMIM). RESULTS: In multivariate-adjusted
      models, alpha diversity was not associated with BMI. However, beta diversity,
      assessed by principal coordinate vectors generated from an unweighted UniFrac
      distance matrix of pairwise comparisons, was associated with BMI (third and
      fourth vectors, P = 0.01 and P = 0.03, respectively). Moreover, beta diversity,
      assessed by cluster membership (three clusters), was also associated with BMI;
      individuals in the first cluster [median BMI 22.35, odds ratio (OR) = 0.48, 95%
      confidence interval (CI) = 0.05-4.34] and second cluster [median BMI 22.55, OR =
      0.26, 95% CI = 0.09-0.75] were significantly less likely to be obese (BMI >=
      27.5) than those in the third cluster (median BMI 23.59). CONCLUSIONS: A beta
      diversity metric of the UGI microbiome is associated with a four fold difference
      in obesity risk in this Asian population. Future studies should address whether
      the UGI microbiome plays a causal role in obesity.

PMID- 25755149
TI  - A Point of Departure in the Comparison of Social and Nonsocial Visual Orienting
      Among Persons With Autism Spectrum Disorders.
AB  - Endogenous visual orienting among children with autism spectrum disorders (ASDs)
      and among typically developing (TD) children was examined using a Posner-type
      task that was modified to include social and nonsocial cues and targets to test
      hypotheses regarding information (social or nonsocial) and cue processing (long
      or short stimulus onset asynchronies (SOAs)). The findings suggest intact
      endogenous orienting to face and mixed face targets using hand and arrow cues
      among children with ASDs who were matched to typically developing children (TDC)
      on the basis of nonverbal mental age (MA) at approximately 8.5 years. The
      findings from this study challenge the notions of a social orienting impairment
      and of mechanical social orienting as the children with ASDs in this study
      demonstrated strong orienting effects in all conditions and social sensitivity in
      the long stimulus onset asynchrony (SOA) condition.

PMID- 25755148
TI  - Community-based walking exercise for peripheral artery disease: An exploratory
      pilot study.
AB  - Supervised walking exercise is an effective treatment to improve walking ability
      of patients with peripheral artery disease (PAD), but few exercise programs in
      community settings have been effective. The aim of this study was to determine
      the efficacy of a community-based walking exercise program with training,
      monitoring and coaching (TMC) components to improve exercise performance and
      patient-reported outcomes in PAD patients. This was a randomized, controlled
      trial including PAD patients (n=25) who previously received peripheral
      endovascular therapy or presented with stable claudication. Patients randomized
      to the intervention group received a comprehensive community-based walking
      exercise program with elements of TMC over 14 weeks. Patients in the control
      group did not receive treatment beyond standard advice to walk. The primary
      outcome in the intent-to-treat (ITT) analyses was peak walking time (PWT) on a
      graded treadmill. Secondary outcomes included claudication onset time (COT) and
      patient-reported outcomes assessed via the Walking Impairment Questionnaire
      (WIQ). Intervention group patients (n=10) did not significantly improve PWT when
      compared with the control group patients (n=10) (mean +/- standard error: +2.1 +/
      0.7 versus 0.0 +/- 0.7 min, p=0.052). Changes in COT and WIQ scores were greater
      for intervention patients compared with control patients (COT: +1.6 +/- 0.8
      versus -0.6 +/- 0.7 min, p=0.045; WIQ: +18.3 +/- 4.2 versus -4.6 +/- 4.2%,
      p=0.001). This pilot using a walking program with TMC and an ITT analysis did not
      improve the primary outcome in PAD patients. Other walking performance and
      patient self-reported outcomes were improved following exercise in community
      settings. Further study is needed to determine whether this intervention improves
      outcomes in a trial employing a larger sample size.

PMID- 25755150
TI  - Navigating venous access: a guide for hospitalists.
AB  - Venous access is the foundation for safe and effective hospital-based care.
      Inpatient providers must have a deep knowledge of the different types of venous
      access devices (VADs), their relative indications, contraindications, and
      appropriateness. However, such knowledge is difficult to come by and usually only
      gleaned through years of clinical experience. To bridge this gap, we provide an
      in-depth summary of the relevant anatomical considerations, physical
      characteristics, advantages, and disadvantages of VADs commonly used in the
      hospital setting. In doing so, we seek to improve the safety and share the
      science of vascular access with frontline clinicians. To aid decision-making, we
      conclude by operationalizing the available data through algorithms that outline
      appropriate vascular access for the hospitalized patient.

PMID- 25755151
TI  - Alemtuzumab based reduced intensity transplantation for pediatric severe aplastic
      anemia.
AB  - BACKGROUND: Hematopoietic cell transplantation (HCT) is curative in patients with
      severe aplastic anemia (SAA). HCT is considered at presentation when a HLA
      matched related donor (MRD) is available and has a high success rate. Unrelated
      donor (URD) transplants are typically undertaken if immunosuppressive therapy
      fails. Increased toxicity and graft rejection are often encountered in this
      setting. PROCEDURE: We report a prospective multi-center trial of HCT in 17
      children with SAA following novel reduced intensity conditioning with
      alemtuzumab, fludarabine and melphalan, and the best available donor. Nine were
      URD transplants matched at 7-8/8 loci, and performed following failure of immune
      suppression. Median follow up was 61 months (range 6-128). RESULTS: All patients
      engrafted. Estimated 5 year event-free and overall-survival was 88% (95%CI 65.7
      96.7). Five year overall survival for MRD and URD transplants was 100% and 78%
      (95%CI 45-93.6) respectively. Median times to neutrophil and platelet engraftment
      was 14 (range 10-27) and 23.5 (range 11-65) days respectively. Treatment related
      mortality was 12%. The incidence of grade II-IV and III-IV acute graft-versus
      host disease was 29% and 18% respectively. At two years, all but one patient
      discontinued immunosuppression successfully. Laboratory measures of immune
      reconstitution normalized at one year and infection rates were low in the latter
      part of the first year. CONCLUSIONS: HCT using this RIC approach was well
      tolerated and successful in achieving donor engraftment and early immune
      reconstitution with good quality of life free of immune suppression. Children
      with SAA can be successfully transplanted using alemtuzumab based conditioning.

PMID- 25755153
TI  - Hydrophilic interaction chromatography: A promising alternative to reversed-phase
      liquid chromatography systems for the purification of small protonated bases.
AB  - The overloaded band profiles of the protonated species of propranolol and
      amitriptyline were recorded under acidic conditions on four classes of stationary
      phases including a conventional silica/organic hybrid material in reversed-phase
      liquid chromatography mode (BEH-C18), an electrostatic repulsion reversed-phase
      liquid chromatography C18 column (BEH-C18+), a poly(styrene-divinylbenzene)
      monolithic column, and a hydrophilic interaction chromatography stationary phase
      (underivatized BEH). The same amounts of protonated bases per unit volume of
      stationary phase were injected in each column (16, 47, and 141 MUg/cm(3)). The
      performance of the propranolol/amitriptyline purification was assessed on the
      basis of the asymmetry of the recorded band profiles and on the selectivity
      factor achieved. The results show that the separation performed under reversed
      phase liquid chromatography like conditions (with BEH-C18, BEH-C18+, and polymer
      monolith materials) provide the largest selectivity factors due to the difference
      in the hydrophobic character of the two compounds. However, they also provide the
      most distorted overloaded band profiles due to a too small loading capacity.
      Remarkably, symmetric band profiles were observed with the hydrophilic
      interaction chromatography column. The larger loading capacity of the hydrophilic
      interaction chromatography column is due to the accumulation of the protonated
      bases into the diffuse water layer formed at the surface of the polar adsorbent.
      This work encourages purifying ionizable compounds on hydrophilic interaction
      chromatography columns rather than on reversed-phase liquid chromatography
      columns.

PMID- 25755152
TI  - Nanoparticles complexed with gene vectors to promote proliferation of human
      vascular endothelial cells.
AB  - Amphiphilic block copolymers containing biodegradable hydrophobic segments of
      depsipeptide based copolymers have been synthesized and explored as gene carriers
      for enhancing proliferation of endothelial cells in vitro. These polymers form
      nanoparticles (NPs) with positive charges on their surface, which could condense
      recombinant plasmids of enhanced green fluorescent protein plasmid and ZNF580
      gene (pEGFP-ZNF580) and protect them against DNase I. ZNF580 gene is efficiently
      transported into EA.hy926 cells to promote their proliferation, whereby the
      transfection efficiency of NPs/pEGFP-ZNF580 is approximately similar to that of
      Lipofectamine 2000. These results indicate that the NPs might have potential as a
      carrier for pEGFP-ZNF580, which could support endothelialization of
      cardiovascular implants. 

PMID- 25755154
TI  - Lysine methylation modulates the protein-protein interactions of yeast cytochrome
      C Cyc1p.
AB  - In recent years, protein methylation has been established as a major
      intracellular PTM. It has also been proposed to modulate protein-protein
      interactions (PPIs) in the interactome. To investigate the effect of PTMs on
      PPIs, we recently developed the conditional two-hybrid (C2H) system. With this,
      we demonstrated that arginine methylation can modulate PPIs in the yeast
      interactome. Here, we used the C2H system to investigate the effect of lysine
      methylation. Specifically, we asked whether Ctm1p-mediated trimethylation of
      yeast cytochrome c Cyc1p, on lysine 78, modulates its interactions with Erv1p,
      Ccp1p, Cyc2p and Cyc3p. We show that the interactions between Cyc1p and Erv1p,
      and between Cyc1p and Cyc3p, are significantly increased upon trimethylation of
      lysine 78. This increase of interaction helps explain the reported facilitation
      of Cyc1p import into the mitochondrial intermembrane space upon methylation. This
      first application of the C2H system to the study of methyllysine-modulated
      interactions further confirms its robustness and flexibility. 

PMID- 25755155
TI  - RE: TERT promoter mutation status as an independent prognostic factor in
      cutaneous melanoma.

PMID- 25755156
TI  - Response.

PMID- 25755157
TI  - Excess body mass index- and waist circumference-years and incident cardiovascular
      disease: the CARDIA study.
AB  - OBJECTIVE: To determine the influence of the total cumulative exposure to excess
      overall and abdominal adiposity on the incidence of cardiovascular disease (CVD).
      METHODS: Prospective study of 4,061 white and black adults without CVD at
      baseline in 1985-1986 (age 18-30 years) from the multicenter, community-based
      CARDIA study. Time-varying excess body mass index (BMI)- and waist circumference
      (WC)-years were calculated as products of the degree and duration of excess
      overall (BMI >= 25 kg/m(2)) and abdominal adiposity [WC >94 cm (men) and >80 cm
      (women)], respectively, collected at up to eight examinations. RESULTS: During a
      median of 24.8 years, there were 125 incident CVD, 62 coronary heart disease
      (CHD), and 33 heart failure (HF) events. Adjusted hazard ratios for CVD, CHD, and
      HF for each additional 50 excess BMI-years were 1.20 (1.08, 1.34), 1.25 (1.07,
      1.46), and 1.45 (1.23, 1.72), respectively. For each 50 excess WC-years, these
      hazard ratios were 1.10 (1.04, 1.18), 1.13 (1.03, 1.24), and 1.22 (1.11, 1.34),
      respectively. Akaike information criterion values were lowest in models
      containing time-varying excess BMI- or WC-years compared to those including time
      varying BMI or WC only. CONCLUSIONS: Excess BMI- and WC-years are predictors of
      the risk of CVD and may provide a better indicator of the cumulative exposure to
      excess adiposity than BMI or WC only.

PMID- 25755159
TI  - We need to talk: Primary care provider communication at discharge in the era of a
      shared electronic medical record.
AB  - BACKGROUND: Poor communication between hospitalists and outpatient physicians can
      contribute to adverse events after discharge. Electronic medical records (EMRs)
      shared by inpatient and outpatient clinicians offer primary care providers (PCPs)
      better access to information surrounding a patient's hospitalization. However,
      the PCP experience and subsequent expectations for discharge communication within
      a shared EMR are unknown. METHODS: We surveyed PCPs 1 year after a shared EMR was
      implemented at our institution to assess PCP satisfaction with current discharge
      communication practices and identify areas for improvement. RESULTS: Seventy-five
      of 124 (60%) clinicians completed the survey. Although most PCPs reported
      receiving automated discharge notifications (71%), only 39% felt that
      notifications plus discharge summaries were adequate for safe transitions of
      care. PCPs expressed that complex hospitalizations necessitated additional
      communication via e-mail or telephone; only 31% reported receiving such
      communication. The content most important in additional communication included
      medication changes, follow-up actions, and active medical issues. CONCLUSIONS:
      Despite optimized access to information provided by a shared EMR, only 52% of
      PCPs were satisfied with current discharge communication. PCPs express a
      continued need for high-touch communication for safe transitions of care. Further
      standardization of discharge communication practices is necessary.

PMID- 25755160
TI  - Osteosarcoma in patients younger than 12 years old without metastases have
      similar prognosis as adolescent and young adults.
AB  - BACKGROUND: Childhood cancer is relatively rare and tends to present specific age
      distribution, as a prognostic factor for some of these diseases. Information on
      how young age affects prognosis, response to chemotherapy, and local control
      options in children versus AYA with osteosarcoma (OST) is minimal. METHODS: In
      order to identify the main differences in clinical pathologic features, surgical
      approaches and survival rates of primary high grade OST of the extremity between
      children (n = 156; <12 years old) and AYA (n = 397; 12-30 years old), the
      institutional database with 553 patients treated by BOTG studies over 15 years
      were reviewed. RESULTS: There were no differences in metastases at diagnosis,
      tumor size, and grade of necrosis between the two age groups. The rate of
      amputation was 30% higher in the children group (P = 0.018). The rate of limb
      salvage surgery using reconstruction with allograft or autograft was 70% higher
      in the children group (P = 0.018) while endoprosthesis rate was 40% higher in the
      AYA group (P = 0.018). The log rank test revealed that survival is similar
      between the two age groups for non-metastatic patients (P = 0.424 for OS and P =
      0.393 for EFS). Metastatic patients of both ages group had higher risk of dying
      compared to non-metastatic (HR 3.283 95% CI 2.581-4.177; P < 0.001). Children
      with metastases at diagnosis had less OS time (P = 0.049) and EFS time (P =
      0.032) than adolescents. CONCLUSION: Non-metastatic OST in preadolescent patients
      does not appear to be significantly different from those seen in AYA patients,
      but has local control challenges. Children presenting with metastases should be
      considered an ultra-high-risk group.

PMID- 25755161
TI  - Health consequences of adverse childhood experiences: a systematic review.
AB  - PURPOSE: Adverse childhood experiences (ACEs) have been associated with negative
      health outcomes, but the evidence has had limited application in primary care
      practice. The purpose of this study was to systematically review the research on
      associations between ACEs and adult health outcomes to inform nurse practitioners
      (NPs) in primary care practice. DATA SOURCES: The databases PubMed, CINAHL,
      PsycINFO, and Social Abstracts were searched for articles published in English
      between 2008 and 2013 using the search term "adverse childhood experiences."
      Forty-two research articles were included in the synthesis. The evidence was
      synthesized and is reported following the preferred reporting items for
      systematic reviews and meta-analysis procedure (PRISMA). CONCLUSIONS: ACEs have
      been associated with health consequences including physical and psychological
      conditions, risk behaviors, developmental disruption, and increased healthcare
      utilization. Generalization of the results is limited by a majority of studies
      (41/42) measuring childhood adversity using self-report measures. IMPLICATIONS
      FOR PRACTICE: NPs are encouraged to incorporate assessment of patients' childhood
      history in routine primary care and to consider the evidence that supports a
      relationship between ACEs and health. Although difficult, talking about patient's
      childhood experiences may positively influence health outcomes.

PMID- 25755162
TI  - Evaluation of a method for the simultaneous quantification of N-nitrosamines in
      water samples based on stir bar sorptive extraction combined with high
      performance liquid chromatography and diode array detection.
AB  - A simple, sensitive, and reliable procedure based on stir bar sorptive extraction
      coupled with high-performance liquid chromatography was applied to simultaneously
      extract and determine three semipolar nitrosamines including N
      nitrosodibutylamine, N-nitrosodiphenylamine, and N-nitrosodicyclohexylamine. To
      achieve the optimum conditions, the effective parameters on the extraction
      efficiency including desorption solvent and time, ionic strength of sample,
      extraction time, and sample volume were systematically investigated. The
      optimized extraction procedure was carried out by stir bars coated with
      polydimethylsiloxane. Under optimum extraction conditions, the performance of the
      proposed method was studied. The linear dynamic range was obtained in the range
      of 0.95-1000 ng/mL (r = 0.9995), 0.26-1000 ng/mL (r = 0.9988) and both 0.32-100
      ng/mL (r = 0.9999) and 100-1000 ng/mL (r = 0.9998) with limits of detection of
      0.28, 0.08, and 0.09 ng/mL for N-nitrosodibutylamine, N-nitrosodiphenylamine, and
      N-nitrosodicyclohexylamine, respectively. The average recoveries were obtained
      >81%, and the reproducibility of the proposed method presented as intra- and
      interday precision were also found with a relative standard deviation <6%.
      Finally, the proposed method was successfully applied to the determination of
      trace amounts of selected nitrosamines in various water and wastewater samples
      and the obtained results were confirmed using mass spectrometry. 

PMID- 25755163
TI  - Shotgun proteome analysis of Bordetella pertussis reveals a distinct influence of
      iron availability on the bacterial metabolism, virulence, and defense response.
AB  - One of the mechanisms involved in host immunity is the limitation of iron
      accessibility to pathogens, which in turn provokes the corresponding
      physiological adaptation of pathogens. This study reports a gel-free nanoLC-MS/MS
      based comparative proteome analysis of Bordetella pertussis grown under iron
      excess and iron-depleted conditions. Out of the 926 proteins covered 98 displayed
      a shift in their abundance in response to low iron availability. Forty-seven of
      them were found to be increased in level while 58 were found with decreased
      protein levels under iron starvation. In addition to proteins previously reported
      to be influenced by iron in B. pertussis, we observed changes in metabolic
      proteins involved in fatty acid utilization and poly-hydroxybutyrate production.
      Additionally, many bacterial virulence factors regulated by the BvgAS two
      component system were found at decreased levels in response to iron limitation.
      These results, together with the increased production of proteins potentially
      involved in oxidative stress resistance, seem to indicate that iron starvation
      provokes changes in B. pertussis phenotype that might shape host-pathogen
      interaction. 

PMID- 25755164
TI  - Long duration of stressful homework as a potential obesogenic factor in children:
      a QUALITY study.
AB  - OBJECTIVE: To examine for the first time whether stressful mental tasks are
      associated with an unfavorable anthropometric profile in children. METHODS: A
      cross-sectional analysis was undertaken in 511 children. A complete
      anthropometric profile was assessed, and children reported their homework
      duration and the presence/absence of stress related to schoolwork. Accelerometers
      and questionnaires provided the other profile of lifestyle components. RESULTS:
      Homework duration was not related to adiposity indicators in children not
      stressed by schoolwork. In boys stressed by schoolwork, significantly higher
      total and trunk body fat percentages were obtained in the high versus low
      duration of homework group. No difference in adiposity indicators was present in
      boys not stressed by schoolwork and in girls. A reduced activity level and an
      increased screen time partly mediated the relationship between homework and
      anthropometric profiles. CONCLUSIONS: Boys with a high workload of homework, when
      combined with the presence of schoolwork-related stress, have unfavorable
      adiposity indicators. This study suggests that more attention should be paid to
      stressful mental work as a potent risk factor for obesity.

PMID- 25755165
TI  - Quantitative determination of fentanyl in newborn pig plasma and cerebrospinal
      fluid samples by HPLC-MS/MS.
AB  - In this study, a selective and sensitive high performance liquid chromatography
      tandem mass spectrometry (HPLC-MS/MS) method requiring low sample volume (<=100
      MUL) was developed and validated for the quantitative determination of the opioid
      drug fentanyl in plasma and cerebrospinal fluid (CSF). A protein precipitation
      extraction with acetonitrile was used for plasma samples whereas CSF samples were
      injected directly on the HPLC column. Fentanyl and (13) C6 -fentanyl (Internal
      Standard) were analyzed in an electrospray ionization source in positive mode,
      with multiple reaction monitoring (MRM) of the transitions m/z 337.0/188.0 and
      m/z 337.0/105.0 for quantification and confirmation of fentanyl, and m/z
      343.0/188.0 for (13) C6 -fentanyl. The respective lowest limits of quantification
      for plasma and CSF were 0.2 and 0.25 ng/mL. Intra- and inter-assay precision and
      accuracy did not exceed 15%, in accordance with bioanalytical validation
      guidelines. The described analytical method was proven to be robust and was
      successfully applied to the determination of fentanyl in plasma and CSF samples
      from a pharmacokinetic and pharmacodynamic study in newborn piglets receiving
      intravenous fentanyl (5 ug/kg bolus immediately followed by a 90-min infusion of
      3 ug/kg/h).

PMID- 25755166
TI  - Perceived core competency achievements of fellowship and non-fellowship-trained
      early career pediatric hospitalists.
AB  - BACKGROUND: The pediatric hospital medicine (PHM) core competencies were
      established in 2010 to identify the specific knowledge base and skill set needed
      to provide the highest quality of care for hospitalized children. The objectives
      of this study were to examine the perceived core competency achievements of
      fellowship-trained and non-fellowship-trained early career pediatric hospitalists
      and identify perceived gaps in our current training models. METHODS: An anonymous
      Web-based survey was distributed in November 2013. Hospitalists within 5 years of
      their residency graduation reported their perceived competency in select PHM core
      competencies. chi(2) and multiprobit regression analyses were utilized. RESULTS:
      One hundred ninety-seven hospitalists completed the survey and were included; 147
      were non-fellowship-trained and 50 were PHM fellowship graduates or current PHM
      fellows. Both groups reported feeling less than competent in sedation and aspects
      of business practice. Non-fellowship-trained hospitalists also reported mean
      scores in the less than competent range in intravenous access/phlebotomy,
      technology-dependent emergencies, performing Plan-Do-Study-Act process and root
      cause analysis, defining basic statistical terms, and identifying research
      resources. Non-fellowship-trained hospitalists reported mean competency scores
      greater than fellowship-trained hospitalists in pain management, newborn care,
      and transitions in care. CONCLUSIONS: Early career pediatric hospitalists report
      deficits in several of the PHM core competencies, which should be considered when
      designing PHM-specific training in the future. Fellowship-trained hospitalists
      report higher levels of perceived competency in many core areas.

PMID- 25755167
TI  - Numerical simulation of waste tyres gasification.
AB  - Gasification is a thermochemical pathway used to convert carbonaceous feedstock
      into syngas (CO and H2) in a deprived oxygen environment. The process can
      accommodate conventional feedstock such as coal, discarded waste including
      plastics, rubber, and mixed waste owing to the high reactor temperature (1000 
      degrees C-1600  degrees C). Pyrolysis is another conversion pathway, yet it is
      more selective to the feedstock owing to the low process temperature (350 
      degrees C-550  degrees C). Discarded tyres can be subjected to pyrolysis,
      however, the yield involves the formation of intermediate radicals additional to
      unconverted char. Gasification, however, owing to the higher temperature and
      shorter residence time, is more opted to follow quasi-equilibrium and being
      predictive. In this work, tyre crumbs are subjected to two levels of gasification
      modelling, i.e. equilibrium zero dimension and reactive multi-dimensional flow.
      The objective is to investigate the effect of the amount of oxidising agent on
      the conversion of tyre granules and syngas composition in a small 20 kW
      cylindrical gasifier. Initially the chemical compositions of several tyre samples
      are measured following the ASTM procedures for proximate and ultimate analysis as
      well as the heating value. The measured data are used to carry out equilibrium
      based and reactive flow gasification. The result shows that both models are
      reasonably predictive averaging 50% gasification efficiency, the devolatilisation
      is less sensitive than the char conversion to the equivalence ratio as
      devolatilisation is always complete. In view of the high attained efficiency, it
      is suggested that the investigated tyre gasification system is economically
      viable.

PMID- 25755168
TI  - CD19: A multifunctional immunological target molecule and its implications for
      Blineage acute lymphoblastic leukemia.
AB  - Over the last 20-30 years CD19 has gained attention as a potential target in the
      therapy of B-cell malignancies. In particular, targeting CD19 with the bispecific
      T-cell engager (BiTE) antibody Blinatumomab and T-cells modified by chimeric
      antigen receptors (CAR) has shown promising efficacy in early phase clinical
      trials for adults and children with precursor B-cell ALL (BCP-ALL). This review
      will discuss the rationale behind targeting CD19 in BCP-ALL and its potential
      importance in BCP-ALL signaling pathways.

PMID- 25755169
TI  - Gastro-oesophageal reflux in young babies: who should be treated?
AB  - Recent guidelines focus on a non-interventionist approach to management of gastro
      oesophageal reflux in infancy and emphasise the importance of explanation,
      reassurance and simple measures such as attention to feeding. Relying on clinical
      history alone leads to over diagnosis of disease, and widely used medications are
      often ineffective for symptom relief and carry significant risk of harm. The
      association between vomiting in infancy and other problems such as crying and
      poor feeding should not be interpreted as implying causality. When there are
      strong pointers to underlying gastro-oesophageal reflux disease, invasive
      investigations are required in order to formulate appropriate intervention. 

PMID- 25755170
TI  - Tachypnoea in a well baby: what to do next?

PMID- 25755171
TI  - Articulating nurse practitioner practice using King's theory of goal attainment.
AB  - PURPOSE: To further understand the interactions between nurse practitioners (NPs)
      and patients, King's nursing theory of goal attainment was applied as the
      conceptual framework to describe the interactions between NPs and patients in the
      primary care setting. DATA SOURCES: Six dyads of NPs and their patients were
      video- and audio-taped over three consecutive clinic visits. For the purposes of
      this arm of the study, the audio-taped interactions were transcribed and then
      coded using King's concepts in her theory of goal attainment. CONCLUSIONS: King's
      theory was applicable to describe NP practice. King's concepts and processes of
      nurse-patient interactions, such as disturbances, mutual goal setting, and
      transactions, were observed in NP-patient interactions. IMPLICATIONS FOR
      PRACTICE: Disturbances during clinical encounters were essential in the
      progression toward goal attainment. Elements, such as social exchange, symptom
      reporting, role explanation, and information around clinical processes
      facilitated relationship building. NPs as practitioners need to be reflective of
      their own practice, embrace disturbances in the clinical encounter, and attend to
      these as opportunities for mutual goal setting.

PMID- 25755172
TI  - Solid-phase microextraction with gas chromatography and mass spectrometry
      determination of benzo(a)pyrene in microcrystalline waxes used as food additives.
AB  - Microcrystalline waxes are mixtures of solid, saturated hydrocarbons mainly
      branched and characterized by a carbon number over C60. They are used as food
      additives for the surface treatment of confectionery and some fruit varieties, in
      chewing gum base, protective coatings, defoaming agents, and surface finishing
      agents. Commission Regulation No 231/2012 established physical and chemical
      specifications for microcrystalline waxes to use in food, and posed a limit of 50
      MUg/kg for benzo(a)pyrene. Due to the low solubility of microcrystalline waxes in
      organic solvents and matrix interferences, analytical determination of
      benzo(a)pyrene represents a difficult task. The official method for indirect
      determination of total polycyclic aromatic hydrocarbons uses unspecific
      spectrophotometric detection and a quite laborious, time- and solvent-consuming
      extraction method. A liquid-liquid partition method followed by solid-phase
      microextraction was developed to isolate benzo(a)pyrene from the bulk of
      saturated hydrocarbons in microcrystalline waxes, with the aim to have a simple
      and effective method to verify compliance with the legal limit. The final
      determination was carried out by gas chromatography coupled to mass spectrometry.
      Good linearity was obtained, along with a recovery of about 80% from the liquid
      liquid partitions. The repeatability of the entire method was <6% and accuracy
      was <3%.

PMID- 25755173
TI  - Identification of novel biomarker candidates for immunohistochemical diagnosis to
      distinguish low-grade chondrosarcoma from enchondroma.
AB  - Chondrosarcoma is the third most common primary bone cancer, requiring surgical
      resection. However, differentiation of low-grade chondrosarcoma (grade 1) from
      enchondroma that is benign and only requires regular follow-up is one of the most
      frequent diagnostic dilemmas facing orthopedic oncologists in clinical
      management. Although multiple techniques are applied to make the distinction,
      immunohistochemistry is an important ancillary technique, especially when a
      histopathological stain of specimen must be obtained in order to guarantee an
      accurate confirmation. Currently, no adequate immunohistochemical diagnostic
      protein biomarkers are available to distinguish low-grade chondrosarcoma from
      enchondroma. To discover novel protein biomarker candidates, an LC-MS/MS approach
      was applied to directly compare formalin-fixed, paraffin-embedded low-grade
      chondrosarcoma with enchondroma tissue samples. The proteomics analysis revealed
      17 protein biomarker candidates. A principle was developed to prioritize the
      candidates using category and ranking. An algorithm, prioritization index of
      biomarker candidates for immunohistochemistry on tissue specimens, was developed
      to rank the candidates inside each category. Using the proteomics data and
      bioinformatics results, the prioritization index of biomarker candidates for
      immunohistochemistry on tissue revealed periostin as a top candidate.
      Immunohistochemical staining of periostin in 23 low-grade chondrosarcoma and 31
      enchondroma tissue specimens disclosed 87% specificity and 70% sensitivity. 

PMID- 25755174
TI  - Nutrition labels influence value computation of food products in the ventromedial
      prefrontal cortex.
AB  - OBJECTIVE: Prevalence of obesity is high in most industrialized nations, and
      therefore, it is crucial to understand contextual factors underlying food choice.
      Nutrition labels are public policy interventions designed to adequately inform
      consumers about nutritional value and overall healthiness of food products. The
      present study examines how different nutrition labels, namely a purely
      information-based label (guideline daily amount, GDA) and a more explicit traffic
      light (TL) label, influence product valuation and choice in a functional MRI
      setting. METHODS: Thirty-five healthy participants across different BMIs were
      instructed to valuate healthy and unhealthy food products in combination with one
      of the two labels and to state their willingness to pay (WTP) for the product.
      RESULTS: The labeling methods significantly influenced participants' WTP. Red TL
      signaling activated parts of the left inferior frontal gyrus/dorsolateral
      prefrontal cortex, a region implicated in self-control in food choice. This
      region, in the case of red signaling, and the posterior cingulate cortex, in the
      case of green signaling, showed increased coupling to the valuation system in the
      ventromedial prefrontal cortex. CONCLUSIONS: Our results suggest that explicitly
      directing attention toward nutritional values using salient nutrition labels
      triggers neurobiological processes that resemble those utilized by successful
      dieters choosing healthier products.

PMID- 25755175
TI  - Observation-status patients in children's hospitals with and without dedicated
      observation units in 2011.
AB  - BACKGROUND: Pediatric observation units (OUs) have demonstrated reductions in
      lengths of stay (LOS) and costs of care. Hospital-level outcomes across all
      observation-status stays have not been evaluated in relation to the presence of a
      dedicated OU in the hospital. OBJECTIVE: To compare observation-status stay
      outcomes in hospitals with and without a dedicated OU. DESIGN: Cross-sectional
      analysis of hospital administrative data. METHODS: Observation-status stay
      outcomes were compared in hospitals with and without a dedicated OU across 4
      categories: (1) LOS, (2) standardized costs, (3) conversion to inpatient status,
      and (4) return care. SETTING/PATIENTS: Observation-status stays in 31 free
      standing children's hospitals contributing observation patient data to the
      Pediatric Health Information System database, 2011. RESULTS: Fifty-one percent of
      the 136,239 observation-status stays in 2011 occurred in 14 hospitals with a
      dedicated OU; the remainder were in 17 hospitals without. The percentage of
      observation-status same-day discharges was higher in hospitals with a dedicated
      OU compared with hospitals without (23.8 vs 22.1, P < 0.001), but risk-adjusted
      LOS in hours and total standardized costs were similar. Conversion to inpatient
      status was higher in hospitals with a dedicated OU (11.06%) compared with
      hospitals without (9.63%, P < 0.01). Adjusted odds of return visits and
      readmissions were comparable. CONCLUSIONS: The presence of a dedicated OU appears
      to have an influence on same-day and morning discharges across all observation
      status stays without impacting other hospital-level outcomes. Inclusion of
      location of care (eg, dedicated OU, inpatient unit, emergency department) in
      hospital administrative datasets would allow for more meaningful comparisons of
      models of hospital care.

PMID- 25755176
TI  - Chemiluminescence detection of MDMA in street drug samples using tris(2,2'
      bipyridine)ruthenium(III).
AB  - Tris(2,2'-bipyridine)ruthenium(II) chemiluminescence was investigated for the
      detection of 3,4-methylenedioxymethamphetamine (MDMA) and several related
      compounds in street drug samples. Optimization using flow injection analysis
      showed that the selectivity of the reagent can be targeted towards the detection
      of secondary amines by altering the pH of the reaction environment. The greater
      selectivity of this mode of detection, compared to UV-absorbance, reduces the
      probability of false positive results from interfering compounds. The detection
      limit for MDMA under these conditions was 0.48 MUM. A HPLC method incorporating
      post-column tris(2,2'-bipyridine)ruthenium(II) chemiluminescence detection was
      applied to the determination of MDMA in five street drug samples. The results
      obtained were in good agreement with quantification performed using traditional
      UV-absorbance detection, which demonstrates the viability of this method for
      confirmatory analysis of drug samples. This is the first report of tris(2,2'
      bipyridine)ruthenium(II) chemiluminescence for the detection of MDMA and related
      amphetamine derivatives.

PMID- 25755177
TI  - Mobilisation of haematopoietic stem cells in paediatric patients, prior to
      autologous transplantation following administration of plerixafor and G-CSF.
AB  - Previous chemotherapy and radiation exposure can make adequate stem cell
      mobilisation prior to autologous transplant extremely difficult in paediatrics.
      Plerixafor, a selective reversible CXCR4 antagonist interferes with CXCR4
      interaction with Stromal cell-derived factor 1 alpha (SDF-1). Combination with
      granulocyte-colony stimulating factor (G-CSF) amplifies G-CSF affects in
      mobilising haematopoietic stem cells. Whilst licensed for use with G-CSF for
      enhancement of mobilisation of haematopoietic stem cells in adults, paediatric
      data for use of plerixafor remain limited. We present a retrospective review of
      outcomes seen with plerixafor and G-CSF to mobilise stem cells heavily pre
      treated paediatric patients with cancer.

PMID- 25755178
TI  - Clinical implications of pharmacogenetic and microarray testing for advanced
      practice nurses.
AB  - PURPOSE: The rapidly changing field of pharmacogenetics requires that advanced
      practice providers have a fundamental foundation in genetics and genetic testing
      on which new knowledge can be built. Testing for allelic variation in the well
      researched Cytochrome P450 pathways and other pathways of drug metabolism is done
      through microarray testing. Understanding the process microarray testing provides
      a framework for understanding pharmacogenetic testing. DATA SOURCES: Genetic,
      pharmacogenetic, and biotechnical literature is reviewed to explain the genetics
      and biotechnology behind testing for allelic variation. Clinical examples of
      applied pharmacogenetic testing in cardiology and psychiatry are provided from
      the nursing literature. CONCLUSION: The advent and practical application of
      inexpensive and available testing aimed to identify genetic variations in
      individual patient metabolism of common and critical medications, necessitates
      that advanced practice registered nurses (APRNs) have a deeper understanding of
      the biotechnology involved in pharmacogenetic and pharmacogenomics testing.
      IMPLICATIONS FOR PRACTICE: Providers with a working knowledge of the microarray
      testing method will have a framework for understanding which patients to test,
      what tests to order, and how to interpret the results of these genetic tests.
      APRNs need to increase their reliance on the interdisciplinary databases that
      maintain the most current and relevant knowledge of pharmacogenetics.

PMID- 25755180
TI  - Determination of N-nitrosamines by automated dispersive liquid-liquid
      microextraction integrated with gas chromatography and mass spectrometry.
AB  - An automated dispersive liquid-liquid microextraction integrated with gas
      chromatography and mass spectrometric procedure was developed for the
      determination of three N-nitrosamines (N-nitroso-di-n-propylamine, N
      nitrosopiperidine, and N-nitroso di-n-butylamine) in water samples. Response
      surface methodology was employed to optimize relevant extraction parameters
      including extraction time, dispersive solvent volume, water sample pH, sodium
      chloride concentration, and agitation (stirring) speed. The optimal dispersive
      liquid-liquid microextraction conditions were 28 min of extraction time, 33 MUL
      of methanol as dispersive solvent, 722 rotations per minute of agitation speed,
      23% w/v sodium chloride concentration, and pH of 10.5. Under these conditions,
      good linearity for the analytes in the range from 0.1 to 100 MUg/L with
      coefficients of determination (r(2) ) from 0.988 to 0.998 were obtained. The
      limits of detection based on a signal-to-noise ratio of 3 were between 5.7 and
      124 ng/L with corresponding relative standard deviations from 3.4 to 5.9% (n =
      4). The relative recoveries of N-nitroso-di-n-propylamine, N-nitrosopiperidine,
      and N-nitroso di-n-butylamine from spiked groundwater and tap water samples at
      concentrations of 2 MUg/L of each analyte (mean +/- standard deviation, n = 3)
      were (93.9 +/- 8.7), (90.6 +/- 10.7), and (103.7 +/- 8.0)%, respectively. The
      method was applied to determine the N-nitrosamines in water samples of different
      complexities, such as tap water, and groundwater, before and after treatment, in
      a local water treatment plant. 

PMID- 25755179
TI  - Urinary extracellular vesicles as reservoirs of altered proteins during the
      pathogenesis of polycystic kidney disease.
AB  - PURPOSE: Recent findings indicate that urinary extracellular vesicles (EVs) might
      reflect the pathophysiological state of urinary system; and that EVs-induced
      ciliary signaling is a possible mechanism of intercellular communication within
      the tract. Here, we aimed to analyze the protein expression of urinary EVs during
      autosomal dominant polycystic kidney disease (ADPKD). EXPERIMENTAL DESIGN: EVs
      were isolated from pooled urine samples of healthy control and ADPKD patients at
      two different stages of the disease and under tolvaptan treatment using the
      double-cushion ultracentrifugation method. Proteins were identified and
      quantified by iTRAQ and multidimensional protein identification technology
      (MudPIT)-based quantitative proteomics. RESULTS: Quantitative analyses identified
      83 differentially expressed EV proteins. Many of these have apical membrane
      origin and are involved in signal transduction pathways of primary cilia, Ca(2+) 
      activated signaling, cell-cycle regulation, and cell differentiation. CONCLUSIONS
      AND CLINICAL RELEVANCE: The reduced AQP-2 and the increased APO-A1 levels
      observed in all ADPKD-affected groups may reflects the impaired renal
      concentrating capability of these patients and correlated with estimated
      glomerular filtration rate decline. The levels of some upregulated proteins
      involved in Ca(2+) -activated signaling declined upon tolvaptan treatment. The
      results obtained suggest that the quantitative proteomics of urinary EVs might be
      useful to monitor proteins difficult to access noninvasively, and thus advance
      our understanding of urinary tract physiology and pathology.

PMID- 25755181
TI  - Cloning & sequence identification of Hsp27 gene and expression analysis of the
      protein on thermal stress in Lucilia cuprina.
AB  - Hsp27, a highly conserved small molecular weight heat shock protein, is widely
      known to be developmentally regulated and heat inducible. Its role in
      thermotolerance is also implicated. This study is a sequel of our earlier studies
      to understand the molecular organization of heat shock genes/proteins and their
      role in development and thermal adaptation in a sheep pest, Lucilia cuprina
      (blowfly), which exhibits unusually high adaptability to a variety of
      environmental stresses, including heat and chemicals. In this report our aim was
      to understand the evolutionary relationship of Lucilia hsp27 gene/protein with
      those of other species and its role in thermal adaptation. We sequence
      characterized the Lchsp27 gene (coding region) and analyzed its expression in
      various larval and adult tissues under normal as well as heat shock conditions.
      The nucleotide sequence analysis of 678 bps long-coding region of Lchsp27
      exhibited closest evolutionary proximity with Drosophila (90.09%), which belongs
      to the same order, Diptera. Heat shock caused significant enhancement in the
      expression of Lchsp27 gene in all the larval and adult tissues examined, however,
      in a tissue specific manner. Significantly, in Malpighian tubules, while the heat
      induced level of hsp27 transcript (mRNA) appeared increased as compared to
      control, the protein level remained unaltered and nuclear localized. We infer
      that Lchsp27 may have significant role in the maintenance of cellular
      homeostasis, particularly, during summer months, when the fly remains exposed to
      high heat in its natural habitat. 

PMID- 25755182
TI  - Fat distribution and mortality: the AGES-Reykjavik Study.
AB  - OBJECTIVE: This study examined associations of regional fat depots with all-cause
      mortality over 11 years of follow-up. METHODS: Data were from 2,187 men and 2,900
      women, aged 66-96 years in the AGES-Reykjavik Study. Abdominal visceral fat and
      subcutaneous fat and thigh intermuscular fat and subcutaneous fat were measured
      by CT. RESULTS: In men, every standard deviation (SD) increment in thigh
      intermuscular fat was related to a significantly greater mortality risk (HR:
      1.17, 95% CI: 1.08-1.26) after adjustment for age, education, smoking, physical
      activity, alcohol, BMI, type 2 diabetes, and coronary heart disease. In women,
      visceral fat (per SD increment) significantly increased mortality risk (HR: 1.13,
      95% CI: 1.03-1.25) while abdominal subcutaneous fat (per SD increment) was
      associated with a lower mortality risk (HR: 0.70, 95% CI: 0.61-0.80). Significant
      interactions with BMI were found in women, indicating that visceral fat was a
      strong predictor of mortality in obese women while abdominal and thigh
      subcutaneous fat were associated with a lower mortality risk in normal-weight and
      overweight women. CONCLUSIONS: Fat distribution is associated with mortality over
      11 years of follow-up independent of overall fatness. The divergent mortality
      risks for visceral fat and subcutaneous fat in women suggest complex
      relationships between overall fatness and mortality.

PMID- 25755183
TI  - Gender disparities in leadership and scholarly productivity of academic
      hospitalists.
AB  - BACKGROUND: Gender disparities still exist for women in academic medicine but may
      be less evident in younger cohorts. Hospital medicine is a new field, and the
      majority of hospitalists are <41 years of age. OBJECTIVE: To determine whether
      gender disparities exist in leadership and scholarly productivity for academic
      hospitalists and to compare the findings to academic general internists. DESIGN:
      Prospective and retrospective observational study. SETTING: University programs
      in the United States. MEASUREMENTS: Gender distribution of (1) academic
      hospitalists and general internists, (2) division or section heads for both
      specialties, (3) speakers at the 2 major national meetings of the 2 specialties,
      and (4) first and last authors of articles from the specialties' 2 major journals
      RESULTS: We found equal gender representation of hospitalists and general
      internists who worked in university hospitals. Divisions or sections of hospital
      medicine and general internal medicine were led by women at 11/69 (16%) and 28/80
      (35%) of university hospitals, respectively (P = 0.008). Women hospitalists and
      general internists were listed as speakers on 146/557 (26%) and 291/580 (50%) of
      the presentations at national meetings, respectively (P < 0.0001), first authors
      on 153/464 (33%) and 423/895 (47%) publications, respectively (P < 0.0001), and
      senior authors on 63/305 (21%) and 265/769 (34%) articles, respectively (P <
      0.0001). CONCLUSIONS: Despite hospital medicine being a newer field, gender
      disparities exist in leadership and scholarly productivity.

PMID- 25755184
TI  - Cardiomyopathy in Marfan syndrome.
AB  - OBJECTIVES: This report aims to evaluate the existence of primary and secondary
      cardiomyopathy in patients with Marfan syndrome (MFS) who underwent surgical
      management for primary cardiovascular sequelae of this genetic disorder.
      Likewise, we aim to determine whether the myocardium in MFS is susceptible to
      ischaemia independent of myocardial protection used during surgery. METHODS:
      Between April 1986 and May 2012, 421 patients with MFS were surgically treated
      for cardiovascular manifestations. Among them, 47 (mean age: 39.45 +/- 12.64,
      median: 36, range: 19-66, years) eventually were surgically treated for
      cardiomyopathy. They were grouped into A: patients who subsequently developed
      ischaemic cardiomyopathy and eventually underwent coronary revascularization for
      coronary artery disease (n = 11); B: patients who subsequently developed end
      stage cardiomyopathy for which a mechanical circulatory support device was
      implanted to support the failing heart (n = 13) and C: patients who subsequently
      developed end-stage cardiomyopathy (n = 23), among whom 21 underwent primary
      heart transplantation, while 2 patients are still waiting for donor hearts.
      RESULTS: Retrospective analysis of the medical records of 47 patients revealed
      the following: In Group A, 3 (27.2%) patients had already existing ischaemic
      cardiomyopathy before the first various cardiovascular surgeries, while ischaemic
      cardiomyopathy in the other 8 (72.7%) developed postoperatively. The interval
      between previous surgery and development of cardiomyopathy was a mean of 8.0 +/-
      07 years. In Group B, 5 (38.4%) had existing primary cardiomyopathy prior to
      surgery, while 8 (61.5%) developed end-stage cardiomyopathy postoperatively. The
      interval between previous surgery and development of cardiomyopathy was a mean of
      9.0 +/- 4 months. In Group C, 5 (21.7%) had been diagnosed with cardiomyopathy
      prior to the cardiovascular surgery, while 18 (78.2%) developed end-stage
      cardiomyopathy postoperatively. The mean interval between previous surgery and
      development of cardiomyopathy was 3 +/- 0.9 years. At a mean follow-up of 9.4 +/-
      1.37 years, the overall survival rate is 51.8%. Categorized based on the surgical
      treatment done for cardiomyopathy, survival rates of 54.5% (the mean follow-up of
      9.35 +/- 1.8 years), 40.1% (mean follow-up of 7.01 +/- 2.8 years) and 70% (mean
      follow-up of 10.5 +/- 2.0 years) were seen in Groups A, B and C, respectively.
      There is no significant difference in survival rates (P = 0.56) among groups.
      Likewise, the type of myocardial protection and duration of ischaemic times were
      not significant (P > 0.78) to the development of cardiomyopathy. CONCLUSIONS: Our
      finding supports the existence of cardiomyopathy in a subset of patients with
      MFS. Marfan cardiomyopathy appears to be independent of the type of myocardial
      protection and duration of ischaemia.

PMID- 25755185
TI  - A 17-year, single-centre experience with the Ross procedure: fulfilling the
      promise of a durable option without anticoagulation?
AB  - OBJECTIVES: For adult patients <60 years with aortic valve disease, the Ross
      procedure is an attractive alternative to a prosthetic aortic valve. The Ross
      procedure enables surgeons to achieve a haemodynamically ideal aortic valve
      replacement. A potential drawback may be long-term durability, which varies
      considerably between series. METHODS: Between 1996 and 2014, 209 patients (mean
      age, 43 +/- 10 years) underwent an elective Ross procedure in our department. In
      78% (n = 161) of patients a bicuspid valve was found. Patients were examined
      clinically and with echocardiography during the follow-up. The mean follow-up was
      7.9 +/- 5 years and was 98% complete. RESULTS: The 30-day mortality rate was 2.4%
      (n = 5). The Kaplan-Meier survival rates at 10 and 15 years were 91 and 85%,
      respectively. In 17 patients (8.3%) the pulmonary autograft had to be reoperated
      on: 12 of them could be repaired; only 5 patients finally underwent prosthetic
      valve replacement. The rate of freedom from reoperation for autograft failure was
      93% and that from reoperation or moderate autograft regurgitation was 87% at 10
      years. Thromboembolic events occurred in 9 patients (0.54%/patient-year) and were
      mostly related to atrial fibrillation. Endocarditis involving the pulmonary
      autograft was observed in 6 patients (0.36%/patient-year). CONCLUSIONS: Pulmonary
      autograft aortic root replacement to treat patients with severe aortic valve
      dysfunction is a challenging procedure. The reoperation rate is higher compared
      with mechanical valve replacement; however, in the majority of patients with
      reoperations in our series the autograft could be saved. Other valve-related
      complications are rare.

PMID- 25755186
TI  - The effect of pulmonary hypertension on ovine tricuspid annular dynamics.
AB  - OBJECTIVES: Pulmonary hypertension (PHT) is associated with tricuspid annular
      dilatation, but the effect of acute increase of pulmonary pressure on three
      dimensional (3D) tricuspid annular dynamics and shape is unknown. Better
      understanding of tricuspid annular dynamics may lead to improved and more durable
      surgical reparative techniques. METHODS: In nine open-chest anaesthetized sheep
      nine sonomicrometry crystals were implanted on the right ventricle while on
      cardiopulmonary bypass. Additional nine crystals were implanted around the
      tricuspid annulus (TA) with one crystal at each commissure defining three
      separate annular regions: anterior, posterior and septal. Two additional
      equidistant crystals were implanted between each commissure, creating three
      segments for every region. Pressure transducers were placed in the left
      ventricular (LV), right ventricular (RV) and right atrium. PHT was induced by
      acute pulmonary artery constriction with a pneumatic occluder. Sonomicrometry and
      echocardiographic data were collected before and after induction of PHT. TA area,
      regional and total perimeter, and 3D annular geometry were calculated from 3D
      crystal coordinates. Regional annular contraction was defined as the percentage
      difference between maximal and minimal region length during the cardiac cycle.
      RESULTS: PHT increased RV pressure from 31 +/- 9 mmHg to 46 +/- 13 mmHg (P =
      0.001) and decreased left ventricular (LV) pressure from 111 +/- 24 mmHg to 78 +/
      36 mmHg (P = 0.018). There was no significant tricuspid regurgitation observed
      with PHT. During PHT, the TA area increased by 12 +/- 13% from 641 +/- 139 mm(2)
      to 721 +/- 177 mm(2) (P = 0.037). The total perimeter increased from 103 +/- 11
      mm to 109 +/- 13 mm (P = 0.02). All annular regions dilated significantly with
      PHT with 8 +/- 10, 5 +/- 5 and 5 +/- 5% increase in anterior, posterior and
      septal annular length, respectively (P < 0.05). PHT reduced regional annular
      contraction in the anterior region only (17 +/- 7 vs 14 +/- 8%; P = 0.02). The TA
      had a complex 3D saddle geometry and the shape of the annulus was altered during
      PHT only in the antero-posterior region. CONCLUSIONS: The changes in tricuspid
      annular conformation, contractility and its 3D geometry observed during acute
      ovine PHT may help in the design of new pathology-specific tricuspid annular
      rings.

PMID- 25755187
TI  - Surgical treatment of recurrent thymoma: is it worthwhile??.
AB  - OBJECTIVES: Radical resection of thymoma is the most important predictor of
      survival; despite a complete resection, 10-30% of patients develop a recurrence.
      The surgical treatment of thymic relapses is an accepted therapeutic approach;
      however, no clear data are available yet regarding the indication for surgery and
      the long-term prognosis of this subset of patients. The aim of our work was to
      review the data of a group of recurrent thymomas treated by surgery, comparing it
      with non-surgical therapy, and analysing the outcome and the prognostic factors.
      METHODS: Between 1980 and 2010, 880 patients with thymoma underwent complete
      macroscopical resection and were followed up for recurrence. Masaoka stage IVa
      and type C thymic tumours were excluded from the study. A total of 82 (9.3%)
      patients developed a recurrence, and 52 (63.4%) were reoperated. The other 21
      patients, originally operated outside, underwent surgical resection of
      recurrence. Finally, 73 patients were operated on for recurrent thymoma and 30
      received medical treatment. This entire cohort represents the subject of the
      study. RESULTS: There were 57 (55.3%) males and 46 (44.7%) females. The median
      time to relapse was 50 months. Sixty-three (61.2%) recurrences were regional, 17
      (16.5%) local, 14 (13.6%) distant, 6 (5.8%) regional and distant, and 3 (2.9%)
      local, regional and distant. No operative mortality was observed. In 50 (68.5%)
      patients, a macroscopic complete resection was accomplished. The 5- and 10-year
      overall survival rates from recurrence were 63 and 37%, respectively. Complete
      surgical resection was associated with a significant better survival when
      compared with incomplete surgical resection and non-surgical treatment (P <
      0.0001). A significant poorer prognosis was observed for multiple versus single
      relapses (P < 0.0001), Masaoka stage III primary tumour versus Masaoka stage I-II
      primary tumour (P = 0.02), distant versus loco-regional relapses (P = 0.05) and
      B3 histotype versus other (P = 0.02). On multivariate analysis, completeness of
      resection, number of metastases, Masaoka stage of primary tumour and site of
      relapse were identified as the only independent predictors of prognosis.
      CONCLUSION: Reoperation for recurrent thymoma is effective and safe, achieving a
      prolonged survival. Complete macroscopic resection and single recurrence are
      associated with better prognosis.

PMID- 25755188
TI  - Seven months: the perfect time to complete the pectus excavatum correction.

PMID- 25755189
TI  - Revisiting the Gram-negative lipoprotein paradigm.
AB  - The processing of lipoproteins (Lpps) in Gram-negative bacteria is generally
      considered an essential pathway. Mature lipoproteins in these bacteria are
      triacylated, with the final fatty acid addition performed by Lnt, an
      apolipoprotein N-acyltransferase. The mature lipoproteins are then sorted by the
      Lol system, with most Lpps inserted into the outer membrane (OM). We demonstrate
      here that the lnt gene is not essential to the Gram-negative pathogen Francisella
      tularensis subsp. tularensis strain Schu or to the live vaccine strain LVS. An
      LVS Deltalnt mutant has a small-colony phenotype on sucrose medium and increased
      susceptibility to globomycin and rifampin. We provide data indicating that the OM
      lipoprotein Tul4A (LpnA) is diacylated but that it, and its paralog Tul4B (LpnB),
      still sort to the OM in the Deltalnt mutant. We present a model in which the Lol
      sorting pathway of Francisella has a modified ABC transporter system that is
      capable of recognizing and sorting both triacylated and diacylated lipoproteins,
      and we show that this modified system is present in many other Gram-negative
      bacteria. We examined this model using Neisseria gonorrhoeae, which has the same
      Lol architecture as that of Francisella, and found that the lnt gene is not
      essential in this organism. This work suggests that Gram-negative bacteria fall
      into two groups, one in which full lipoprotein processing is essential and one in
      which the final acylation step is not essential, potentially due to the ability
      of the Lol sorting pathway in these bacteria to sort immature apolipoproteins to
      the OM. IMPORTANCE: This paper describes the novel finding that the final stage
      in lipoprotein processing (normally considered an essential process) is not
      required by Francisella tularensis or Neisseria gonorrhoeae. The paper provides a
      potential reason for this and shows that it may be widespread in other Gram
      negative bacteria.

PMID- 25755190
TI  - A more flexible lipoprotein sorting pathway.
AB  - Lipoprotein biogenesis in Gram-negative bacteria occurs by a conserved pathway,
      each step of which is considered essential. In contrast to this model, LoVullo
      and colleagues demonstrate that the N-acyl transferase Lnt is not required in
      Francisella tularensis or Neisseria gonorrhoeae. This suggests the existence of a
      more flexible lipoprotein pathway, likely due to a modified Lol transporter
      complex, and raises the possibility that pathogens may regulate lipoprotein
      processing to modulate interactions with the host. 

PMID- 25755191
TI  - The phosphorylation flow of the Vibrio harveyi quorum-sensing cascade determines
      levels of phenotypic heterogeneity in the population.
AB  - Quorum sensing (QS) is a communication process that enables a bacterial
      population to coordinate and synchronize specific behaviors. The bioluminescent
      marine bacterium Vibrio harveyi integrates three autoinducer (AI) signals into
      one quorum-sensing cascade comprising a phosphorelay involving three hybrid
      sensor kinases: LuxU; LuxO, an Hfq/small RNA (sRNA) switch; and the
      transcriptional regulator LuxR. Using a new set of V. harveyi mutants lacking
      genes for the AI synthases and/or sensors, we assayed the activity of the quorum
      sensing cascade at the population and single-cell levels, with a specific focus
      on signal integration and noise levels. We found that the ratios of kinase
      activities to phosphatase activities of the three sensors and, hence, the extent
      of phosphorylation of LuxU/LuxO are important not only for the signaling output
      but also for the degree of noise in the system. The pools of phosphorylated
      LuxU/LuxO per cell directly determine the amounts of sRNAs produced and,
      consequently, the copy number of LuxR, generating heterogeneous quorum-sensing
      activation at the single-cell level. We conclude that the ability to drive the
      heterogeneous expression of QS-regulated genes in V. harveyi is an inherent
      feature of the architecture of the QS cascade. IMPORTANCE: V. harveyi possesses
      one of the most complex quorum-sensing (QS) cascades known, using three different
      autoinducers (AIs) to control the induction of, e.g., bioluminescence, virulence
      factors, and biofilm and exoprotease production. We constructed various V.
      harveyi mutants to study the impact of each component and subsystem of the QS
      signaling cascade on QS activation at the population and single-cell levels. We
      found that the output was homogeneous only in the presence of all AIs. In the
      absence of any one AI, QS activation varied from cell to cell, resulting in
      phenotypic heterogeneity. This study elucidates a molecular design principle
      which enables a tightly integrated signaling cascade to control the expression of
      diverse phenotypes within a genetically homogeneous population.

PMID- 25755192
TI  - Characterization of a novel antisense RNA in the major pilin locus of Neisseria
      meningitidis influencing antigenic variation.
AB  - Expression of type four pili (Tfp) is essential for virulence in Neisseria
      meningitidis. Pili mediate adhesion, bacterial aggregation, and DNA uptake. In N.
      meningitidis, the major pilin subunit is encoded by the pilE gene. In some
      strains, PilE is subject to phase and antigenic variation, which can alter Tfp
      properties and together offer a possible mechanism of immune escape. Pilin
      expression and antigenic variation can be modulated in response to environmental
      cues; however, the precise mechanisms of such regulation remain unclear. We
      identified a promoter in the pilE locus, 3' of the pilE coding sequence, on the
      antisense (AS) strand which is conserved in meningococci. We show that this
      promoter directs transcription of an AS RNA that is expressed during specific
      growth phases and in response to salt stress. Furthermore, we demonstrate that
      the transcript encompasses sequences complementary to the entire pilE coding
      sequence and 5' untranslated region. AS RNAs can regulate the gene on the sense
      strand by altering transcript stability or translation. However, by using
      Northern blotting, quantitative reverse transcription-PCR (RT-PCR), and Western
      blotting, we found no significant AS RNA-dependent changes in pilE transcript or
      protein level. Instead, our data indicate that the AS RNA influences pilin
      antigenic variation. This work provides further insights into the complex
      regulation of pilin expression and variation in pathogenic Neisseria. IMPORTANCE:
      Pathogenic Neisseria spp. express type four pili (Tfp) which are important for
      adhesion, aggregation and transformation. Some strains of N. meningitidis are
      able to vary the sequence of the major subunit (PilE) of the Tfp. The mechanisms
      underlying this variation are not fully defined, but the process requires several
      noncoding elements that are found adjacent to the pilE gene. In this work, we
      identified a cis-encoded RNA antisense to pilE in N. meningitidis. By using
      Northern blotting and RT-PCR analysis, we found that the RNA is expressed in
      stationary phase or following salt stress. Our work also indicates that this RNA
      does not significantly affect pilE or pilin expression levels but instead appears
      to modulate pilin variation.

PMID- 25755193
TI  - Quality of life among pediatric patients with cancer: Contributions of time since
      diagnosis and parental chronic stress.
AB  - BACKGROUND: Pediatric cancer is associated with a host of negative psychosocial
      consequences; however, outcomes vary extensively suggesting a need to better
      understand this variation. Empirical research suggests a positive association
      between time since diagnosis (TSD) and Quality of Life (QoL). In addition to TSD,
      family stressors have been found to be particularly important in predicting QoL
      among children. The current study examined parental chronic stress beyond TSD in
      explanation of QoL functioning among a sample of pediatric patients with cancer.
      PROCEDURE: Participants included 43 pediatric patients aged 5-18 years (M(age) =
      10.2 +/- 3.6) who were undergoing oncological treatment. Parents reported on TSD,
      child's QoL, and their own chronic stress. RESULTS: TSD was associated with
      greater physical functioning (r = 0.30, P < 0.05). Parental chronic stress was
      associated with poorer emotional (r = -0.54, P < 0.01), physical (r = -0.41, P <
      0.01), and social functioning (r = -0.44, P < 0.01). Further, hierarchal linear
      regression analyzes indicated parental chronic stress contributed incrementally
      beyond TSD in the explanation of physical (beta = -0.37, t = -2.58, P < 0.01),
      emotional (beta = -0.47, t = -3.51, P < 0.00), and social functioning (beta = 
      0.38, t = -2.67, P < 0.01). CONCLUSIONS: Parental chronic stress is associated
      with reduced levels of emotional, physical, and social functioning among
      pediatric patients. Future research is needed to further investigate the process
      by which chronic stress within the family interferes with adaptive coping among
      pediatric patients. In addition, clinical services may benefit from increased
      consideration of family factors, such as parental chronic stress, during
      oncological treatment.

PMID- 25755194
TI  - Infant pulmonary function testing in chronic pneumonitis of infancy due to
      surfactant protein C mutation.
AB  - Pulmonary function testing is a vital tool in evaluation and management of adult
      ILD patients and is rarely overlooked during workup. However, there is paucity of
      data regarding its usefulness in management of infants with suspected
      interstitial lung disease. In this paper, we present the contribution of infant
      pulmonary function testing (iPFT) to the management of two infants with biopsy
      confirmed chronic pneumonitis of infancy due to surfactant protein C mutation. We
      have productively and safely used serial iPFT for decision making both during
      diagnosis and follow-up of these infants.

PMID- 25755195
TI  - Reporting in studies of protein biomarkers of prognosis in colorectal cancer in
      relation to the REMARK guidelines.
AB  - PURPOSE: The REMARK guidelines give authors comprehensive and specific advice on
      the complete and transparent reporting of studies of prognostic tumor markers.
      The aim of this study was to use the REMARK guidelines to evaluate the quality of
      reporting in a sample of studies assessing tissue-based protein markers for
      survival after resection of colorectal cancer. EXPERIMENTAL DESIGN: Eighty
      pertinent articles were scored according to their conformity to 26 items derived
      from the REMARK criteria. RESULTS: Overall, on a scale of adequacy of reporting
      that potentially ranged from 26 to 78, the median for these studies was 60
      (interquartile range 54-64) and several criteria were adequately covered in a
      large proportion of studies. However, others were either not dealt with or
      inadequately covered, including description of the study design (35%), definition
      of survival endpoints (48%), adjuvant therapy (54%), follow-up procedures and
      time (59%), neoadjuvant therapy (63%), inclusion/exclusion criteria (73%),
      multivariable modeling methods and results (74%), and discussion of study
      limitations (85%). CONCLUSIONS AND CLINICAL RELEVANCE: Inadequacies in
      presentation militate against comparability among protein marker studies and
      undermine the generalizability of their findings. The quality of reporting could
      be improved if journal editors were to require authors to ensure that their work
      satisfied the REMARK criteria.

PMID- 25755196
TI  - Simultaneous enantioselective determination of isocarbophos and its main
      metabolite isocarbophos oxon in rice, soil, and water by chiral liquid
      chromatography and tandem mass spectrometry.
AB  - An efficient enantioselective method for the simultaneous determination of
      isocarbophos and its main metabolite isocarbophos oxon in rice, soil, and water
      was developed using liquid chromatography with tandem mass spectrometry. The
      enantioseparation was performed on a Chiralpak AD-3R column at 30 degrees C using
      gradient elution. Target compounds were extracted from soil and rice using
      acetonitrile with omission of a clean-up procedure, while a C18 solid-phase
      extraction column was used for water samples. Quantification was achieved using
      matrix-matched calibration. The overall mean recoveries for isocarbophos and
      isocarbophos oxon enantiomers from the five matrices were 89.7-103 and 90.1
      98.7%, with relative standard deviations of 2.1-5.4 and 2.5-4.7%, respectively.
      Moreover, the absolute configurations of isocarbophos oxon enantiomers were
      determined by liquid chromatography with tandem mass spectrometry through
      incubation of each isocarbophos enantiomer in soil, the first eluting enantiomer
      being confirmed as (R)-(-)-isocarbophos oxon. The proposed method was applied to
      real soil samples and satisfactory results were obtained. 

PMID- 25755197
TI  - The insecticidal activity and action mode of an imidacloprid analogue, 1-(3
      pyridylmethyl)-2-nitroimino-imidazolidine.
AB  - Neonicotinoids, such as imidacloprid, are key insecticides extensively used for
      control of Nilaparvata lugens. However, imidacloprid resistance has been reported
      in many Asian countries in recent years. To understand the roles of the chlorine
      atom of pyridyl group on insecticidal activity and resistance, the atom was
      removed to generate an imidacloprid analogue DC-Imi (DesChlorine Imidacloprid).
      DC-Imi showed significantly higher toxicity than imidacloprid in the susceptible
      strain of N. lugens, but had medium level cross-resistance in an imidacloprid
      resistant strain. In Xenopus oocyte expressed nicotinic acetylcholine receptors
      (nAChRs) Nlalpha1/rbeta2, the inward currents evoked by DC-Imi were detected and
      could be blocked by typical nAChRs antagonist dihydro-beta-erythroidine
      (DHbetaE), which demonstrated that DC-Imi acted as an agonist on insect nAChRs.
      The efficacy of DC-Imi on Nlalpha1/rbeta2 was 1.8-fold higher than that of
      imidacloprid. In addition, the influence of an imidacloprid resistance associated
      mutation (Y151S) on agonist potencies was evaluated. Compared with the wild-type
      receptor, the mutation reduced maximal inward current of DC-Imi to 55.6% and
      increased half maximal effective concentration (EC50 ) to 3.53-fold. Compared
      with imidacloprid (increasing EC50 to 2.38-fold of wild-type receptor), Y151S
      mutation decreased DC-Imi potency more significantly. The results indicated that
      the selective and possibly high toxicities could be achieved through the
      modification of 6-chloro-3-pyridyl group in imidacloprid and other
      neonicotinoids. 

PMID- 25755198
TI  - Fitness is a determinant of the metabolic response to endurance training in
      adolescents at risk of type 2 diabetes mellitus.
AB  - OBJECTIVE: The purpose of this prospective cohort study was to determine whether
      changes in cardiorespiratory fitness are associated with the metabolic response
      to endurance training in adolescents at risk of type 2 diabetes mellitus (T2DM).
      METHODS: Seventy-three overweight and obese adolescents completed a 6-month
      endurance exercise intervention. Total fat mass, trunk fat mass, visceral adipose
      tissue, and liver fat were assessed with dual energy X-ray absorptiometry and
      magnetic resonance imaging spectroscopy. RESULTS: The change in cardiorespiratory
      fitness with training was independently associated with reductions in BMI z-score
      (beta = -0.09; P = 0.006), total fat mass (beta = -1.40; P = 0.007), trunk fat
      mass (beta = -0.70; P = 0.01), and liver fat (beta = -1.80; P = 0.053).
      Adolescents within the highest tertile of change in fitness were 4.67 (95% CI:
      1.15-13.73; P = 0.03), 11.90 (95% CI: 2.37-59.77; P = 0.002), and 6.21 (95% CI:
      1.14-33.99; P = 0.035) times more likely to experience decreases in body weight,
      BMI, and liver fat compared with adolescents in the lowest tertile. CONCLUSIONS:
      The changes in adiposity and hepatic triglyceride content in response to
      endurance training are significantly related to the increase in cardiorespiratory
      fitness in adolescents at risk of T2DM.

PMID- 25755199
TI  - In reference to "Use of paracentesis in hospitalized patients with decompensated
      cirrhosis and ascites: Opportunities for quality improvement".

PMID- 25755200
TI  - Long-term results of the AIEOP LNH-97 protocol for childhood lymphoblastic
      lymphoma.
AB  - BACKGROUND: Treatment intensification was considered a suitable strategy to
      increase the cure rate of lymphoblastic lymphoma (LBL) in children. PROCEDURE:
      The AIEOP LNH-97 trial was run between 1997 and 2007 for newly diagnosed LBL in
      patients aged less than 18 years. Treatment schedule was based on the previous,
      LSA2-L2 derived, AIEOP LNH-92 protocol. Modifications included: increased dose of
      upfront cyclophosphamide and methotrexate, use of l-Asparaginase during induction
      therapy, intensive block therapy for slow responders, and late intensification
      ("Reinduction") for patients with advanced stage disease. Total therapy duration
      was 12 months for stage I and II, and 24 months for stage III and IV. Central
      nervous system prophylaxis did not include cranial irradiation. RESULTS: 114
      eligible patients were enrolled, 84 males and 30 females; median age was 9 years.
      Complete remission was obtained in 98% of patients. After a median follow-up time
      of seven years, 29 patients failed due to progression of disease (n = 2), relapse
      (n = 25), or second malignancy (n = 2). The 7-year overall survival was 82%
      (standard error [SE] 4%) and the 7-year event-free survival was 74% (SE 4%). No
      subgroup showed significantly different event free survival. None of the patients
      died of front line chemotherapy-related toxicity. CONCLUSIONS: Treatment
      intensification was associated with good outcome in children and adolescents with
      LBL, with limited toxicity. Prognosis after relapse was better for patients who
      underwent allogeneic hematopoietic stem cell transplantation. Measurements of
      biological markers and treatment response are necessary for achieving further
      improvement through more accurate identification and stratification of patients
      at risk of disease relapse.

PMID- 25755201
TI  - Characterization of pulmonary function in Duchenne Muscular Dystrophy.
AB  - Decline in pulmonary function in Duchenne Muscular Dystrophy (DMD) contributes to
      significant morbidity and reduced longevity. Spirometry is a widely used and
      fairly easily performed technique to assess lung function, and in particular lung
      volume; however, the acceptability criteria from the American Thoracic Society
      (ATS) may be overly restrictive and inappropriate for patients with neuromuscular
      disease. We examined prospective spirometry data (Forced Vital Capacity [FVC] and
      peak expiratory flow [PEF]) from 60 DMD patients enrolled in a natural history
      cohort study (median age 10.3 years, range 5-24 years). Expiratory flow-volume
      curves were examined by a pulmonologist and the data were evaluated for
      acceptability using ATS criteria modified based on the capabilities of patients
      with neuromuscular disease. Data were then analyzed for change with age,
      ambulation status, and glucocorticoid use. At least one acceptable study was
      obtained in 44 subjects (73%), and 81 of the 131 studies (62%) were acceptable.
      The FVC and PEF showed similar relative changes in absolute values with
      increasing age, i.e., an increase through 10 years, relative stabilization from
      10-18 years, and then a decrease at an older age. The percent predicted, FVC and
      PEF showed a near linear decline of approximately 5% points/year from ages 5 to
      24. Surprisingly, no difference was observed in FVC or PEF by ambulation or
      steroid treatment. Acceptable spirometry can be performed on DMD patients over a
      broad range of ages. Using modified ATS criteria, curated spirometry data,
      excluding technically unacceptable data, may provide a more reliable means of
      determining change in lung function over time.

PMID- 25755202
TI  - Fluorescence life-time imaging and steady state polarization for examining
      binding of fluorophores to gold nanoparticles.
AB  - Nanocomposites as multifunctional agents are capable of combing imaging and cell
      biology technologies. The conventional methods used for validation of the
      conjugation process of nanoparticles (NPs) to fluorescent molecules such as
      spectroscopy analysis and surface potential measurements, are not sufficient. In
      this paper we present a new and highly sensitive procedure that uses the
      combination of (1) fluorescence spectrum, (2) fluorescence lifetime, and (3)
      steady state fluorescence polarization measurements. We characterize and analyze
      gold NPs with Lucifer yellow (LY) surface coating as a model. We demonstrate the
      ability to differentiate between LY-GNP (the conjugated complex) and a mixture of
      coated NP and free dyes. We suggest the approach for neuroscience applications
      where LY is used for detecting and labeling cells, studying morphology and
      intracellular communications. Histograms of Fluorescence lifetime imaging (FLIM)
      of free LY dye (Left) in comparison to the conjugated dye to gold nanoparticles,
      LY-GNP (Middle) enable the differentiation between LY-GNP (the conjugated
      complex) and a mixture of coated NP and free dyes (Right). 

PMID- 25755203
TI  - Grounding cognitive-level processes in behavior: the view from dynamic systems
      theory.
AB  - Marr's seminal work laid out a program of research by specifying key questions
      for cognitive science at different levels of analysis. Because dynamic systems
      theory (DST) focuses on time and interdependence of components, DST research
      programs come to very different conclusions regarding the nature of cognitive
      change. We review a specific DST approach to cognitive-level processes: dynamic
      field theory (DFT). We review research applying DFT to several cognitive-level
      processes: object permanence, naming hierarchical categories, and inferring
      intent, that demonstrate the difference in understanding of behavior and
      cognition that results from a DST perspective. These point to a central challenge
      for cognitive science research as defined by Marr-emergence. We argue that
      appreciating emergence raises questions about the utility of computational-level
      analyses and opens the door to insights concerning the origin of novel forms of
      behavior and thought (e.g., a new chess strategy). We contend this is one of the
      most fundamental questions about cognition and behavior. 

PMID- 25755204
TI  - A combined tryptic peptide and winged peptide internal standard approach for the
      determination of alpha-lactalbumin in dairy products by ultra high performance
      liquid chromatography with tandem mass spectrometry.
AB  - A robust ultra high performance liquid chromatography with tandem mass
      spectrometry method at peptide level was established for measuring alpha
      lactalbumin in various dairy products. An isotope-labeled winged peptide
      (VKKILDKVG*INYW*LAHKALCSEKL) with extra amino acids of the sequence of signature
      peptide concatenated at each end as the internal standard was spiked in samples
      to participate in the whole tryptic digestion process. The peptide VG*INYW*LAHK
      that resulted from the isotope-labeled winged peptide was used as the final
      isotopically labeled internal standard of the alpha-lactalbumin signature peptide
      (VGINYWLAHK) during the quantitative analysis. The contents of alpha-lactalbumin
      in samples were calculated based on the equimolar relationship between the alpha
      lactalbumin protein and signature peptide. The optimized molar ratio of trypsin
      to protein (1:60) and enzymatic digestion time (5 h) could not only improve the
      digestion efficiency and reduce the cost, but also minimize the period of sample
      pretreatment. Considering the robustness of the current method using the
      isotopically labeled internal standard and acceptable measurement cost, its
      application may promote the development of nutrient investigation and quality
      control of alpha-lactalbumin in dairy products. This protein analysis method
      might provide a new reference strategy for food analysis and quantitative protein
      analysis. 

PMID- 25755206
TI  - Insights into inpatients with poor vision: A high value proposition.
AB  - BACKGROUND: Vision impairment is an under-recognized risk factor for adverse
      events among hospitalized patients, yet vision is neither routinely tested nor
      documented for inpatients. Low-cost ($8 and up) nonprescription "readers" may be
      a simple, high-value intervention to improve inpatients' vision. We aimed to
      study initial feasibility and efficacy of screening and correcting inpatients'
      vision. METHODS: From June 2012 through January 2014 we began testing whether
      participants' vision corrected with nonprescription lenses for eligible
      participants failing a vision screen (Snellen chart) performed by research
      assistants (RAs). Descriptive statistics and tests of comparison, including t
      tests and chi(2) tests, were used when appropriate. All analyses were performed
      using Stata version 12 (StataCorp, College Station, TX). RESULTS: Over 800
      participants' vision was screened (n = 853). Older (>=65 years; 56%) participants
      were more likely to have insufficient vision than younger (<65 years; 28%; P <
      0.001). Nonprescription readers corrected the majority of eligible participants'
      vision (82%, 95/116). DISCUSSION: Among an easily identified subgroup of
      inpatients with poor vision, low-cost readers successfully corrected most
      participants' vision. Hospitalists and other clinicians working in the inpatient
      setting can play an important role in identifying opportunities to provide high
      value care related to patients' vision.

PMID- 25755207
TI  - Pilocarpine-induced convulsive activity is limited by multidrug transporters at
      the rodent blood-brain barrier.
AB  - As a result of the growing availability of genetically engineered mouse lines,
      the pilocarpine post-status epilepticus (SE) model of temporal lobe epilepsy is
      increasingly used in mice. A discrepancy in pilocarpine sensitivity in FVB/N wild
      type versus P-glycoprotein (PGP)-deficient mice precipitated the investigation of
      the interaction between pilocarpine and two major multidrug transporters at the
      blood-brain barrier. Doses of pilocarpine necessary for SE induction were
      determined in male and female wild-type and PGP-deficient mice. Brain and plasma
      concentrations were measured following low (30-50 mg?kg(-1) i.p.) and/or high
      (200 mg?kg(-1) i.p.) doses of pilocarpine in wild-type mice, and mice lacking
      PGP, breast cancer resistance protein (BCRP), or both transporters, as well as in
      rats with or without pretreatment with lithium chloride or tariquidar.
      Concentration equilibrium transport assays (CETA) were performed using cells
      overexpressing murine PGP or BCRP. Lower pilocarpine doses were necessary for SE
      induction in PGP-deficient mice. Brain-plasma ratios were higher in mice lacking
      PGP or PGP and BCRP, which was also observed after pretreatment with tariquidar
      in mice and in rats. Lithium chloride did not change brain penetration of
      pilocarpine. CETA confirmed transport of pilocarpine by PGP and BCRP. Pilocarpine
      is a substrate of PGP and BCRP at the rodent blood-brain barrier, which restricts
      its convulsive action. Future studies to reveal whether strain differences in
      pilocarpine sensitivity derive from differences in multidrug transporter
      expression levels are warranted. 

PMID- 25755208
TI  - Innate immune modulation in chronic obstructive pulmonary disease: moving closer
      toward vitamin D therapy.
AB  - Chronic obstructive pulmonary disease (COPD) is one of the most common
      respiratory diseases and a major cause of morbidity and mortality worldwide.
      Disturbed innate immune processes characterize the pathogenesis of COPD. Vitamin
      D deficiency is very common in COPD patients and has been associated with disease
      severity. Interestingly, mechanistic evidence from animal and in vitro studies
      has demonstrated important innate immunomodulatory functions of vitamin D,
      including anti-inflammatory, antioxidative, and antimicrobial functions. This
      review discusses in detail how the innate immunomodulatory functions of vitamin D
      may have therapeutic potential in COPD patients. The remaining challenges
      associated with vitamin D therapy in COPD patients are also discussed. 

PMID- 25755205
TI  - The role of androgens in metabolism, obesity, and diabetes in males and females.
AB  - OBJECTIVE: In men, androgen deprivation contributes to the development of
      metabolic syndrome and type 2 diabetes (T2D). In women, androgen excess
      predisposes to insulin resistance and T2D. There is a bidirectional modulation of
      glucose homeostasis by androgens in males and females that is analyzed in this
      review. METHODS: We reviewed the literature in both rodents and humans on the
      role of androgens and the androgen receptor (AR) in the control of glucose and
      energy metabolism in health, obesity, and T2D. RESULTS: Sex-specific activation
      of AR in the hypothalamus, skeletal muscle, liver, adipose tissue, and pancreatic
      islet beta-cells accounts for maintenance or disruption in energy metabolism and
      glucose homeostasis. CONCLUSIONS: We argue that AR is a target to prevent
      androgen-related metabolic disorders.

PMID- 25755209
TI  - Evaluating an etiologically relevant platform for therapy development for
      temporal lobe epilepsy: effects of carbamazepine and valproic acid on acute
      seizures and chronic behavioral comorbidities in the Theiler's murine
      encephalomyelitis virus mouse model.
AB  - Central nervous system infections can underlie the development of epilepsy, and
      Theiler's murine encephalomyelitis virus (TMEV) infection in C57BL/6J mice
      provides a novel model of infection-induced epilepsy. Approximately 50-65% of
      infected mice develop acute, handling-induced seizures during the infection.
      Brains display acute neuropathology, and a high number of mice develop
      spontaneous, recurrent seizures and behavioral comorbidities weeks later. This
      study characterized the utility of this model for drug testing by assessing
      whether antiseizure drug treatment during the acute infection period attenuates
      handling-induced seizures, and whether such treatment modifies associated
      comorbidities. Male C57BL/6J mice infected with TMEV received twice-daily
      valproic acid (VPA; 200 mg/kg), carbamazepine (CBZ; 20 mg/kg), or vehicle during
      the infection (days 0-7). Mice were assessed twice daily during the infection
      period for handling-induced seizures. Relative to vehicle-treated mice, more CBZ
      treated mice presented with acute seizures; VPA conferred no change. In mice
      displaying seizures, VPA, but not CBZ, reduced seizure burden. Animals were then
      randomly assigned to acute and long-term follow-up. VPA was associated with
      significant elevations in acute (day 8) glial fibrillary acidic protein
      (astrocytes) immunoreactivity, but did not affect NeuN (neurons)
      immunoreactivity. Additionally, VPA-treated mice showed improved motor
      performance 15 days postinfection (DPI). At 36 DPI, CBZ-treated mice traveled
      significantly less distance through the center of an open field, indicative of
      anxiety-like behavior. CBZ-treated mice also presented with significant
      astrogliosis 36 DPI. Neither CBZ nor VPA prevented long-term reductions in NeuN
      immunoreactivity. The TMEV model thus provides an etiologically relevant platform
      to evaluate potential treatments for acute seizures and disease modification. 

PMID- 25755210
TI  - Nonsteroidal anti-inflammatory drugs-exacerbated respiratory disease in
      adolescents.
AB  - BACKGROUND: There has been no study investigating nonsteroidal anti-inflammatory
      drugs (NSAIDs)-exacerbated respiratory disease (NERD) exclusively in childhood.
      Therefore, in the current study, the authors aimed to evaluate the diagnostic
      features, clinical characteristics, and follow-up of adolescents diagnosed with
      NERD. METHODS: The patients who were consecutively diagnosed with NERD between
      January 2011, and November 2013, included in the study. Oral provocation test
      (OPT) with at least 2 different NSAIDs was used to confirm NSAID hypersensitivity
      in patients with underlying asthma/chronic rhinosinusitis/nasal polyps. All
      patients were followed regularly in 3-month intervals by the Pediatric Allergy
      and Otorhinolaryngology Department for asthma, allergic rhinitis, or chronic
      rhinosinusitis with or without nasal polyps. RESULTS: A total of 10 adolescents
      with NERD were included in the study. The mean age of the patients at the time of
      diagnosis was 14.9 +/- 1.5 years. Hives or angioedema accompanied respiratory
      complaints induced by NSAIDs. The mean duration of follow-up was 28.9 +/- 12.4
      months. All patients had asthma except 1 with asymptomatic bronchial
      hyperreactivity. Asthma of patients was well-controlled with moderate dose of
      inhaled corticosteroids. Chronic rhinosinusitis with or without nasal polyps
      developed in 2 patients. Aspirin desensitization was required in these 2 patients
      with recurrent nasal polyps. CONCLUSION: NERD in childhood has much more
      favorable clinical characteristics and course than in adulthood. Few adolescents
      with NERD refer with typical chronic upper respiratory tract complaints. The
      asthma component seems to be mild and is well controlled in the short-term follow
      up.

PMID- 25755211
TI  - Safe integration of nelarabine into intensive chemotherapy in newly diagnosed T
      cell acute lymphoblastic leukemia: Children's Oncology Group Study AALL0434.
AB  - BACKGROUND: Nelarabine has shown impressive single agent clinical activity in T
      cell acute lymphoblastic leukemia (T-ALL), but has been associated with
      significant neurotoxicities in heavily pre-treated patients. We showed previously
      that it was safe to add nelarabine to a BFM-86 chemotherapy backbone (AALL00P2).
      Children's Oncology Group (COG) AALL0434 is a Phase III study designed to test
      the safety and efficacy of nelarabine when incorporated into a COG augmented BFM
      based regimen, which increases exposure to agents with potential neurotoxicity
      compared to the historical AALL00P2 regimen. PROCEDURE: AALL0434 included a
      safety phase to assess nelarabine toxicity. Patients with high-risk (HR) T-ALL
      were randomized to receive Capizzi-style escalating methotrexate (MTX) plus
      pegaspargase or high dose (HD) MTX with/without six five-days courses of
      nelarabine. We report results from 94 patients who participated in the initial
      safety phase of the study. RESULTS: There were no differences in the incidence of
      peripheral motor neuropathies, sensory neuropathies or central neurotoxicities
      among those randomized to the nelarabine (n = 47) and non-nelarabine arms (n =
      47). CONCLUSIONS: The addition of nelarabine to COG-augmented BFM chemotherapy
      regimen is safe and feasible. The ongoing AALL0434 Efficacy Phase will determine
      whether the addition of nelarabine treatment improves outcome for patients with T
      ALL.

PMID- 25755212
TI  - Efficacy response in CF patients treated with ivacaftor: post-hoc analysis.
AB  - Clinical studies in patients with cystic fibrosis and G551D-CFTR showed that the
      group treated with ivacaftor had improved clinical outcomes. To better understand
      the effect of ivacaftor therapy across the distribution of individual FEV(1)
      responses, data from Phase 3 studies (STRIVE/ENVISION) were re-examined. In this
      post-hoc analysis of patients (n = 209) who received 48 weeks of ivacaftor or
      placebo, patients were assigned to tertiles according to FEV(1) response. These
      groups were then used to evaluate response (FEV(1), sweat chloride, weight, CFQ
      R, and pulmonary exacerbation). The number needed to treat (NNT) was calculated
      for specific thresholds for each outcome. Across all tertiles, numerical
      improvements in FEV(1), sweat chloride, CFQ-R and the frequency of pulmonary
      exacerbations were observed in ivacaftor-treated patients: the treatment
      difference versus placebo was statistically significant for all outcomes in the
      upper tertile and for some outcomes in the lower and middle tertiles. The NNT for
      a >= 5% improvement in %predicted FEV(1) was 1.90, for a >= 5% body weight
      increase was 5.74, and to prevent a pulmonary exacerbation was 3.85. This
      analysis suggests that the majority of patients with clinical characteristics
      similar to STRIVE/ENVISION patients have the potential to benefit from ivacaftor
      therapy.

PMID- 25755213
TI  - Thirty Years After Marr's Vision: Levels of Analysis in Cognitive Science.
AB  - Thirty years after the publication of Marr's seminal book Vision (Marr, 1982) the
      papers in this topic consider the contemporary status of his influential
      conception of three distinct levels of analysis for information-processing
      systems, and in particular the role of the algorithmic and representational level
      with its cognitive-level concepts. This level has (either implicitly or
      explicitly) been downplayed or eliminated both by reductionist neuroscience
      approaches from below that seek to account for behavior from the implementation
      level and by Bayesian approaches from above that seek to account for behavior in
      purely computational-level terms. 

PMID- 25755214
TI  - Quantitative and rapid estimations of human sub-surface skin mass using ultra
      high-resolution spectral domain optical coherence tomography.
AB  - Non-invasive and quantitative estimations for the delineation of sub-surface
      tumor margins could greatly aid in the early detection and monitoring of the
      morphological appearances of tumor growth, ensure complete tumor excision without
      the unnecessary sacrifice of healthy tissue, and facilitate post-operative follow
      up for recurrence. In this study, a high-speed, non-invasive, and ultra-high
      resolution spectral domain optical coherence tomography (UHR-SDOCT) imaging
      platform was developed for the quantitative measurement of human sub-surface skin
      mass. With a proposed robust, semi-automatic analysis, the system can rapidly
      quantify lesion area and shape regularity by an en-face-oriented algorithm.
      Various sizes of nylon sutures embedded in pork skin were used first as a phantom
      to verify the accuracy of our algorithm, and then in vivo, feasibility was proven
      using benign human angiomas and pigmented nevi. Clinically, this is the first
      step towards an automated skin lesion measurement system. In vivo optical
      coherence tomography (OCT) image of angioma (A). Thin red arrows point to a blood
      vessel (BV). 

PMID- 25755215
TI  - Determination of phthalate esters in Chinese spirits using isotope dilution gas
      chromatography with tandem mass spectrometry.
AB  - Phthalate esters are additives used in polyvinylchloride and are found as
      contaminants in many food products. An isotope dilution mass spectrometry
      technique has been developed for accurate analysis of 16 phthalate esters in
      Chinese spirits by adopting the 16 corresponding isotope-labeled phthalate
      esters. The ethanol in the spirit sample was first removed by heating with a
      water bath at 100 degrees C with a stream of nitrogen, after which the residue
      was extracted with n-hexane twice. The phthalates collected were identified and
      quantified by gas chromatography with tandem mass spectrometry in multiple
      reaction monitoring mode. The spiking recoveries of 16 analytes ranged from 94.3
      to 105.3% with relative standard deviation values of <6.5%. The detection limits
      for 16 analytes were <10.0 ng/g. The expanded relative uncertainties were from
      3.0 to 14%. A survey was performed on Chinese spirits from the market. Six of the
      nine analyzed samples were contaminated by phthalates. Di-n-butyl phthalate and
      di-2-ethylhexyl phthalate showed higher detection frequency and concentrations.
      This isotope dilution gas chromatography with tandem mass spectrometry method is
      simple, rapid, accurate, and highly sensitive, which qualifies as a candidate
      reference method for the determination of phthalates in spirits. 

PMID- 25755216
TI  - Markers of metabolic health in children differ between weekdays--the result of
      unhealthier weekend behavior.
AB  - OBJECTIVE: The aim of this study was to investigate whether indicators of
      metabolic health fluctuate during the week in a group of children posing
      unhealthier physical activity, sedentary time, and sleep during weekends compared
      to weekdays. METHODS: A total of 807 eight- to eleven-year-old children had valid
      metabolic health markers from one, two, or three measurements contributing 2190
      to 2240 observations of metabolic health markers. The weekly variation was tested
      using linear mixed models. RESULTS: Homeostatic model assessment of insulin
      resistance (HOMAIR), triglycerides, leptin (all P < 0.001), and adiponectin (P =
      0.03) decreased from Monday to Friday, whereas ghrelin increased (P < 0.001).
      HOMAIR , triglycerides, and leptin were 35%, 28%, and 33% higher on Mondays
      compared to Fridays, respectively, and ghrelin was 7% lower on Mondays compared
      to Fridays (all P < 0.001). CONCLUSIONS: The large weekly variation in HOMAIR ,
      triglycerides, and leptin was likely the result of unhealthier behaviors during
      weekends. These findings have public health relevance and raise methodological
      issues that should ideally be taken into account in future studies.

PMID- 25755217
TI  - Stepping toward discharge: Level of ambulation in hospitalized patients.
AB  - Little information is available on how active adult patients are during their
      hospitalization. The purpose of this study is to describe the level of ambulation
      in hospitalized patients. This was a cohort study of ambulatory patients from 3
      hospital medical-surgical units conducted March 2014 through July 2014. Patients
      wore an accelerometer upon admission to the unit until discharge to home. Sensor
      placement and data review were performed as part of routine care. Step counts
      were merged with administrative and clinical data for analysis. Data were
      available on 777 patients who had at least 24 hours of monitoring prior to
      discharge. The sample included 57% females, and 55% were nonwhite. The median
      total step count over 24 hours was 1158 (interquartile range: 636-2238). Patients
      who were older accrued fewer steps compared to younger patients (962 vs 1294, P <
      0.0001). For patients who had at least 48 hours of monitoring (n = 378), there
      was an increase from 811 steps in the first 24 hours to 1188 steps in the final
      24 hours prior to discharge. More frequent documentation was associated with
      higher step counts (P <= 0.001). We found that a diverse sample of hospitalized
      adult patients accrued over 1000 steps in the 24 hours prior to discharge home.

PMID- 25755218
TI  - Influence of upper airway abnormalities on the control of severe asthma: a cross
      sectional study.
AB  - BACKGROUND: A better understanding of severe uncontrolled asthma (UA) in the
      upper airways is needed. The aims of this study were to assess the prevalence of
      upper airway abnormalities and their associations with UA. METHODS: An
      observational study enrolled individuals with severe asthma. Sociodemographic and
      clinical questionnaires regarding asthma, rhinosinusitis, and laryngopharyngeal
      reflux (LPR) were administered. Skin-prick tests and fiber optic
      nasolaryngoscopies were also performed. Descriptive statistical analysis was
      performed, using a multiple Poisson regression model to obtain adjusted
      prevalence ratios (PRs) and to identify the clinical profiles associated with the
      highest and lowest percentages of the dependent variable, lack of asthma control.
      RESULTS: The sample consisted of 64 participants who were divided into 2 groups
      according to asthma control. Thus, group I comprised 27 individuals with severe
      controlled asthma (CA), and group II consisted of 37 individuals with UA. Women
      represented 87.5% of the study population. The median age was 54 years, and 86%
      of the sample had rhinosinusitis. Relevant associations were detected between UA
      and hyposmia (PR = 2.04), hypersensitivity to nonsteroidal anti-inflammatory
      drugs (NSAIDs) (PR = 1.45), arytenoids hyperemia (PR = 1.45), LPR (PR = 1.37), a
      positive family history of asthma (PR = 1.35), onset of asthma at age 10 years or
      older (PR = 0.59), and swelling of the vocal cords (PR = 0.54). CONCLUSION: This
      study found a very high prevalence of rhinosinusitis in patients with severe
      asthma as well as associations between UA and hyposmia, hypersensitivity to
      NSAIDs, arytenoids hyperemia, and LPR. Clinical profiles prone to UA were
      identified.

PMID- 25755219
TI  - Is low dose hydroxyurea the solution to the global epidemic of sickle cell
      disease?

PMID- 25755221
TI  - Optimization of modified dispersive liquid-liquid microextraction coupled with
      high-performance liquid chromatography for the simultaneous preconcentration and
      determination of nitrazepam and midazolam drugs: An experimental design.
AB  - A simple, sensitive, and rapid microextraction method, namely, ultrasound
      assisted surfactant-enhanced emulsification microextraction based on the
      solidification of floating organic droplet method coupled with high-performance
      liquid chromatography was developed for the simultaneous preconcentration and
      determination of nitrazepam and midazolam. The significant parameters affecting
      the extraction efficiency were considered using Plackett-Burman design as a
      screening method. To obtain the optimum conditions with consideration of the
      selected significant variables, a Box-Behnken design was used. The
      microextraction procedure was performed using 29.1 MUL of 1-undecanol, 1.36%
      (w/v) of NaCl, 10.0 MUL of sodium dodecyl sulfate (25.0 MUg mL(-1)), and 1.0 MUL
      of Tween80 (25.0 MUg mL(-1)) as an emulsifier in an extraction time of 20.0 min
      at pH 7.88. In order to investigate the validation of the developed method, some
      validation parameters including the linear dynamic range, repeatability, limit of
      detection, and recoveries were studied under the optimum conditions. The
      detection limits of the method were 0.017 and 0.086 ng mL(-1) for nitrazepam and
      midazolam, respectively. The extraction recovery percentages for the drugs
      studied were above 91.0 with acceptable relative standard deviation. The proposed
      methodology was successfully applied for the determination of these drugs in a
      number of human serum samples.

PMID- 25755220
TI  - Cutting, dicing, healing and sealing: the molecular surgery of tRNA.
AB  - All organisms encode transfer RNAs (tRNAs) that are synthesized as precursor
      molecules bearing extra sequences at their 5' and 3' ends; some tRNAs also
      contain introns, which are removed by splicing. Despite commonality in what the
      ultimate goal is (i.e., producing a mature tRNA), mechanistically, tRNA splicing
      differs between Bacteria and Archaea or Eukarya. The number and position of tRNA
      introns varies between organisms and even between different tRNAs within the same
      organism, suggesting a degree of plasticity in both the evolution and persistence
      of modern tRNA splicing systems. Here we will review recent findings that not
      only highlight nuances in splicing pathways but also provide potential reasons
      for the maintenance of introns in tRNA. Recently, connections between defects in
      the components of the tRNA splicing machinery and medically relevant phenotypes
      in humans have been reported. These differences will be discussed in terms of the
      importance of splicing for tRNA function and in a broader context on how tRNA
      splicing defects can often have unpredictable consequences.

PMID- 25755222
TI  - Green synthesis of Ni-Nb oxide catalysts for low-temperature oxidative
      dehydrogenation of ethane.
AB  - The straightforward solid-state grinding of a mixture of Ni nitrate and Nb
      oxalate crystals led to, after mild calcination (T<400  degrees C),
      nanostructured Ni-Nb oxide composites. These new materials efficiently catalyzed
      the oxidative dehydrogenation (ODH) of ethane to ethylene at a relatively low
      temperature (T<300  degrees C). These catalysts appear to be much more stable
      than the corresponding composites prepared by other chemical methods; more than
      90 % of their original intrinsic activity was retained after 50 h with time on
      stream. Furthermore, the stability was much less affected by the Nb content than
      in composites prepared by classical "wet" syntheses. These materials, obtained in
      a solvent-free way, are thus promising green and sustainable alternatives to the
      current Ni-Nb candidates for the low-temperature ODH of ethane. 

PMID- 25755223
TI  - Polyunsaturated fatty acid regulation of adipocyte FADS1 and FADS2 expression and
      function.
AB  - OBJECTIVE: Polyunsaturated fatty acids (PUFAs) regulate fatty acid desaturase
      (FADS1, FADS2) expression in the liver; however, it is unknown whether PUFAs
      regulate FADS in adipocytes. This is important to study considering reports that
      link altered desaturase activity with adipose tissue PUFA profiles, body weight,
      and whole-body glucose homeostasis. Therefore, the present study aimed to
      determine the direct effects of PUFAs on FADS expression in differentiated 3T3-L1
      adipocytes. METHODS: Differentiated 3T3-L1 adipocytes were treated with either
      alpha-linolenic (ALA), linoleic (LA), eicosapentaenoic (EPA), or arachidonic acid
      (AA). Gene expression, protein abundance, and cellular PUFA content were analyzed
      by real-time RT-PCR, Western blotting, and gas chromatography, respectively.
      RESULTS: Fads1 and Fads2 gene expression was reduced by EPA and AA, but not ALA
      or LA. Reductions in gene expression were reflected in FADS2 protein levels, but
      not FADS1. Treating cells with ALA and LA led to significant increases in the
      cellular content of downstream PUFAs. Neither ALA nor EPA changed docosahexaenoic
      acid content. CONCLUSIONS: Differentiated 3T3-L1 adipocytes have a functional
      FADS pathway that can be regulated by PUFA. Therefore, this common adipocyte
      model is suitable to study dietary regulation of the FADS pathway.

PMID- 25755224
TI  - Clinical and 22-item Sino-Nasal Outcome Test symptom patterns in primary headache
      disorder patients presenting to otolaryngologists with "sinus" headaches, pain or
      pressure.
AB  - BACKGROUND: The objective of this work was to study patient and 22-item Sino
      Nasal Outcome Test (SNOT-22) characteristics in primary headache disorders
      (PHDs). METHODS: Retrospective chart review of "sinus" headache/pressure/pain
      patients was conducted. Patients that had rhinosinusitis excluded (negative
      endoscopy/computed tomography [CT]), and neurologist-confirmed PHD were studied.
      Patterns in symptom and SNOT-22 items were analyzed by network visualization and
      cluster analysis. RESULTS: Forty-six patients met study criteria. Forty-three
      (93.5%) reported "need to blow nose" and 40 (86.9%) reported postnasal drainage.
      Sneezing was reported by 37 (80.4%) patients, "blockage/congestion of nose" by 33
      (71.8%), and "runny nose by 32 (69.6%) patients. The median SNOT-22 score was 54
      (interquartile range [IQR], 40 to 63). Past history included neurological
      diagnoses (60%), rhinologic disease (39%; chronic rhinosinusitis [CRS], rhinitis,
      recurrent acute sinusitis), asthma (28%), and allergen-sensitivity (26%).
      Previous sinonasal surgery had been performed in 41%. Network layout and cluster
      analysis identified 2 patient clusters and 2 symptom clusters. Two-thirds (31) of
      patients formed a tight cluster (cluster 1) linking to a symptom cluster of
      psychosocial items wrapped tightly with "facial pain/pressure." The remaining one
      third of patients (cluster 2) linked to rhinologic symptoms loosely grouped away
      from "facial pressure/pain." In contrast to patients in cluster 2, patients in
      cluster 1 were predominantly female (p < 0.04), had significantly higher (p <
      0.0001) median SNOT-22 scores (60 vs 34; IQR, 53 to 67 vs 17 to 42), were more
      likely to have migraine history (p = 0.058), and reported being "sad" (p <
      0.0001) or "embarrassed" (p < 0.006). CONCLUSION: Prominent rhinologic symptoms
      can be present in PHD patients in the absence of rhinosinusitis. In particular,
      high symptom-burden/SNOT-22 scores and high psychosocial symptoms should raise
      suspicion of PHD when endoscopy and/or CT results do not correlate with symptoms.

PMID- 25755226
TI  - Ethical concerns about adaptive randomization.

PMID- 25755225
TI  - Participation in pediatric oncology research protocols: Racial/ethnic, language
      and age-based disparities.
AB  - BACKGROUND: Survival rates in pediatric oncology have improved dramatically, in
      part due to high patient participation in clinical trials. Although racial/ethnic
      inequalities in clinical trial participation have been reported in adults,
      pediatric data and studies comparing participation rates by socio-demographic
      characteristics are scarce. The goal of this study was to assess differences in
      research protocol participation for childhood cancer by age, sex, race/ethnicity,
      parental language, cancer type, and insurance status. PROCEDURE: Data on
      enrollment in any protocol, biospecimen, or therapeutic protocols were collected
      and analyzed for newly diagnosed pediatric patients with cancer from 2008-2012 at
      Rady Children's Hospital. RESULTS: Among the 353 patients included in the
      analysis, 304 (86.1%) were enrolled in any protocol. Enrollment in biospecimen
      and therapeutic protocols was 84.2% (261/310) and 81.1% (206/254), respectively.
      Logistic regression analyzes revealed significant enrollment underrepresentation
      in any protocol for Hispanics compared to Non-Hispanic whites (81% vs. 91%; Odds
      Ratio [OR], 0.43; 95% Confidence Interval [CI], 0.21-0.90; P = 0.021) and among
      children of Spanish-speaking vs. English-speaking parents (78% vs. 89%; OR, 0.45;
      95%CI, 0.23-0.87; P = 0.016). Compared to patients aged 0-4 years, significant
      underrepresentation was also found among patients 15-21 years old (92% vs.72%;
      OR, 0.21; 95% CI, 0.09-0.48; P < 0.001). Similar trends were observed when
      analyzing enrollment in biospecimen and therapeutic protocols separately.
      CONCLUSIONS: There was significant underrepresentation in protocol participation
      for Hispanics, children of Spanish-speaking parents, and patients ages 15-21.
      Research is needed to understand barriers to research participation among these
      groups underrepresented in pediatric oncology clinical trials.

PMID- 25755227
TI  - Response.

PMID- 25755228
TI  - Hydrogen and electron transfer between microorganisms: an annotated selection of
      World Wide Web sites relevant to the topics in environmental microbiology.

PMID- 25755229
TI  - When to say when: How aggressively to care for children with multiply relapsed
      cancer?

PMID- 25755230
TI  - Macroprolactinaemia: a biological diagnostic strategy from the study of 222
      patients.
AB  - OBJECTIVES: Gel filtration chromatography (GFC), the gold standard for
      macroprolactinaemia (MPRL) diagnosis, is a slow, costly and labour-intensive
      method. To limit the number of GFC required, we evaluated two screening tests for
      MPRL: prolactin (PRL) recovery after polyethylene glycol (PEG) precipitation and
      PRL concentration ratio, derived from two assays, each having different big-big
      PRL cross-reactivities.In some patients, MPRL is characterised by clinical
      symptoms which can be associated with an excess of monomeric PRL. We compared the
      monomeric PRL concentration obtained from GFC with the PRL concentration i) on a
      cobas e 601 analyser and ii) in the supernatant after PEG precipitation. DESIGN
      AND METHODS: We studied hyperprolactinaemic sera subjected to physician-ordered
      GFC, between February 2013 and July 2014. We performed PEG precipitation (to
      evaluate the PRL concentration and rate of recovery in the supernatant) and two
      PRL assays: RIA and electrochemiluminescent assay (ECLIA), on a Roche cobas e 601
      analyser, and calculated the RIA/ECLIA ratio. RESULTS: Among the 222 sera, we
      were able to diagnose or exclude MPRL in 72.1% of cases, based solely on the
      ratio and/or recovery. In the remaining cases, GFC was necessary for making a
      diagnosis. Elevated monomeric PRL was present in 10.9% of macroprolactinaemic
      sera. In the case of MPRL, both PRL measurements on the cobas analyser and in the
      supernatant weakly correlated with monomeric PRL values obtained from GFC.
      CONCLUSIONS: The combination of PEG and RIA/ECLIA ratio analysis reduced the
      number of necessary GFC. However, GFC is essential in MPRL cases to evaluate the
      monomeric PRL concentration.

PMID- 25755232
TI  - Habitual coffee intake, genetic polymorphisms, and type 2 diabetes.
AB  - BACKGROUND: The association between coffee intake and type 2 diabetes may be
      modulated by common genetic variation. OBJECTIVE: The purpose of this study was
      to examine the association between habitual coffee intake and the risk of type 2
      diabetes and to determine whether this association varied by genetic
      polymorphisms related to type 2 diabetes in Korean adults. DESIGN AND METHODS: A
      population-based cohort study over a follow-up of 4 years was conducted. A total
      of 4077 Korean men and women aged 40-69 years with a normal glucose level at
      baseline were included. Coffee intake was assessed using a validated food
      frequency questionnaire, and incident type 2 diabetes or prediabetes was defined
      by oral glucose tolerance test or fasting blood glucose test. The genomic DNA
      samples were genotyped with the Affymetrix Genome-Wide Human SNP Array 5.0, and
      nine single-nucleotide polymorphisms related to type 2 diabetes in East Asian
      populations were extracted. RESULTS: A total of 120 cases of type 2 diabetes and
      1128 cases of prediabetes were identified. After adjustment for potential
      confounding factors, we observed an inverse association, but without any clear
      linear trend, between coffee intake and the combined risk of type 2 diabetes and
      prediabetes. We found that inverse associations between habitual coffee intake
      and the combined risk of type 2 diabetes and prediabetes were limited to those
      with the T-allele (GT/TT) of rs4402960 in IGF2BP2, those with the G-allele
      (GG/GC) of rs7754840 in CDKAL1, or those with CC of rs5215 in KCNJ11. CONCLUSION:
      We found a lower risk of prediabetes and type 2 diabetes combined with coffee
      intake among individuals with the GT/TT of IGF2BP2 rs4402960, GG/GC of CDKAL1
      rs7754840, or CC of KCNJ11 rs5215, which are known to be related to type 2
      diabetes in East Asians.

PMID- 25755231
TI  - Clinical characteristics and molecular genetic analysis of 22 patients with
      neonatal diabetes from the South-Eastern region of Turkey: predominance of non
      KATP channel mutations.
AB  - BACKGROUND: Neonatal diabetes mellitus (NDM) is a rare form of monogenic diabetes
      and usually presents in the first 6 months of life. We aimed to describe the
      clinical characteristics and molecular genetics of a large Turkish cohort of NDM
      patients from a single centre and estimate an annual incidence rate of NDM in
      South-Eastern Anatolian region of Turkey. DESIGN AND METHODS: NDM patients
      presenting to Diyarbakir Children State Hospital between 2010 and 2013, and
      patients under follow-up with presumed type 1 diabetes mellitus, with onset
      before 6 months of age were recruited. Molecular genetic analysis was performed.
      RESULTS: Twenty-two patients (59% males) were diagnosed with NDM (TNDM-5; PNDM
      17). Molecular genetic analysis identified a mutation in 20 (95%) patients who
      had undergone a mutation analysis. In transient neonatal diabetes (TNDM)
      patients, the genetic cause included chromosome 6q24 abnormalities (n=3), ABCC8
      (n=1) and homozygous INS (n=1). In permanent neonatal diabetes (PNDM) patients,
      homozygous GCK (n=6), EIF2AK3 (n=3), PTF1A (n=3), and INS (n=1) and heterozygous
      KCNJ11 (n=2) mutations were identified. Pancreatic exocrine dysfunction was
      observed in patients with mutations in the distal PTF1A enhancer. Both patients
      with a KCNJ11 mutation responded to oral sulphonylurea. A variable phenotype was
      associated with the homozygous c.-331C>A INS mutation, which was identified in
      both a PNDM and TNDM patient. The annual incidence of PNDM in South-East
      Anatolian region of Turkey was one in 48 000 live births. CONCLUSIONS: Homozygous
      mutations in GCK, EIF2AK3 and the distal enhancer region of PTF1A were the
      commonest causes of NDM in our cohort. The high rate of detection of a mutation
      likely reflects the contribution of new genetic techniques (targeted next
      generation sequencing) and increased consanguinity within our cohort.

PMID- 25755233
TI  - Parent-reported outcomes of a shared decision-making portal in asthma: a practice
      based RCT.
AB  - BACKGROUND: Electronic health record (EHR)-linked patient portals are a promising
      approach to facilitate shared decision-making between families of children with
      chronic conditions and pediatricians. This study evaluated the feasibility,
      acceptability, and impact of MyAsthma, an EHR-linked patient portal supporting
      shared decision-making for pediatric asthma. METHODS: We conducted a 6-month
      randomized controlled trial of MyAsthma at 3 primary care practices. Families
      were randomized to MyAsthma, which tracks families' asthma treatment concerns and
      goals, children's asthma symptoms, medication side effects and adherence, and
      provides decision support, or to standard care. Outcomes included the feasibility
      and acceptability of MyAsthma for families, child health care utilization and
      asthma control, and the number of days of missed school (child) and work
      (parent). Descriptive statistics and longitudinal regression models assessed
      differences in outcomes between study arms. RESULTS: We enrolled 60 families, 30
      in each study arm (mean age 8.3 years); 57% of parents in the intervention group
      used MyAsthma during at least 5 of the 6 study months. Parents of children with
      moderate to severe persistent asthma used the portal more than others; 92% were
      satisfied with MyAsthma. Parents reported that use improved their communication
      with the office, ability to manage asthma, and awareness of the importance of
      ongoing attention to treatment. Parents in the intervention group reported that
      children had a lower frequency of asthma flares and intervention parents missed
      fewer days of work due to asthma. CONCLUSIONS: Use of an EHR-linked asthma portal
      was feasible and acceptable to families and improved clinically meaningful
      outcomes.

PMID- 25755234
TI  - Chronic hepatitis E resolved by reduced immunosuppression in pediatric kidney
      transplant patients.
AB  - At present, transient asymptomatic hepatitis E virus (HEV) infection is common
      among healthy adults in Western Europe, as reported by blood transfusion
      services. In immune-suppressed patients HEV infection is often without clinical
      symptoms, but without therapeutic intervention it may become chronic and lead to
      cirrhosis. This report describes the course of chronic HEV infection after kidney
      transplantation in 2 children, who cleared the virus after reduction in
      immunosuppressive therapy. If aminotransferase levels continue to be moderately
      elevated after transplantation, HEV infection should be excluded. 

PMID- 25755235
TI  - Diversity and inclusion training in pediatric departments.
AB  - BACKGROUND AND OBJECTIVE: The diversifying US population of children necessitates
      assessing the diversity of the pediatric academic workforce and its level of
      cultural competency training. Such data are essential for workforce and
      educational policies. METHODS: An 8-question survey was sent to 131 US pediatric
      chairs to assess plans for diversity, targeted groups, departmental diversity,
      diversity measures, perceived success in diversity, and presence and type of
      cultural competency training. RESULTS: In all, 49.6% of chairs responded, and
      three-quarters of them reported having a plan for diversity, which targeted
      racial; ethnic; gender; lesbian, gay, bisexual, and transgender; disabled; and
      social class groups. Of the residents, 75% were women, as compared with 54% of
      faculty and 26% of chairs. Racial and ethnic diversity was limited among
      trainees, faculty, and leaders; <10% of each group was African American,
      Hispanic, or Native American. Asian Americans were more common among trainees
      (15%-33%) but were less common in faculty and leadership positions (0%-14%).
      Lesbian, gay, bisexual, and transgender physicians were represented in some
      groups. Measures of diversity included the number of trainees and faculty,
      promotion success, climate assessments, and exit interviews. Overall, 69% of
      chairs reported being successful in diversity efforts. A total of 90% reported
      cultural competency training for trainees, and 74% reported training for faculty
      and staff. Training in cultural competency included linguistic training,
      primarily in Spanish. CONCLUSIONS: Pipeline issues for minorities are ongoing
      challenges. Pediatric leadership needs more representation of racial and ethnic
      minorities, women, and LGBT. Suggestions for workforce and educational policies
      are made.

PMID- 25755236
TI  - Prediction models for neonatal health care-associated sepsis: a meta-analysis.
AB  - BACKGROUND AND OBJECTIVES: Blood culture is the gold standard to diagnose
      bloodstream infection but is usually time-consuming. Prediction models aim to
      facilitate early preliminary diagnosis and treatment. We systematically reviewed
      prediction models for health care-associated bloodstream infection (HABSI) in
      neonates, identified superior models, and pooled clinical predictors. DATA
      SOURCES: LibHub, PubMed, and Web of Science. METHODS: The studies included
      designed prediction models for laboratory-confirmed HABSI or sepsis. The target
      population was a consecutive series of neonates with suspicion of sepsis
      hospitalized for >= 48 hours. Clinical predictors had to be recorded at time of
      or before culturing. Methodologic quality of the studies was assessed. Data
      extracted included population characteristics, total suspected and laboratory
      confirmed episodes and definition, clinical parameter definitions and odds
      ratios, and diagnostic accuracy parameters. RESULTS: The systematic search
      revealed 9 articles with 12 prediction models representing 1295 suspected and 434
      laboratory-confirmed sepsis episodes. Models exhibit moderate-good methodologic
      quality, large pretest probability range, and insufficient diagnostic accuracy.
      Random effects meta-analysis showed that lethargy, pallor/mottling, total
      parenteral nutrition, lipid infusion, and postnatal corticosteroids were
      predictive for HABSI. Post hoc analysis with low-gestational-age neonates
      demonstrated that apnea/bradycardia, lethargy, pallor/mottling, and poor
      peripheral perfusion were predictive for HABSI. Limitations include clinical and
      statistical heterogeneity. CONCLUSIONS: Prediction models should be considered as
      guidance rather than an absolute indicator because they all have limited
      diagnostic accuracy. Lethargy and pallor and/or mottling for all neonates as well
      as apnea and/or bradycardia and poor peripheral perfusion for very low birth
      weight neonates are the most powerful clinical signs. However, the clinical
      context of the neonate should always be considered.

PMID- 25755237
TI  - Off-label use of inhaled nitric oxide after release of NIH consensus statement.
AB  - BACKGROUND: Inhaled nitric oxide (iNO) therapy is an off-label medication in
      infants <34 weeks' gestational age. In 2011, the National Institutes of Health
      released a statement discouraging routine iNO use in premature infants. The
      objective of this study was to describe utilization patterns of iNO in American
      NICUs in the years surrounding the release of the National Institutes of Health
      statement. We hypothesized that iNO prescription rates in premature infants have
      remained unchanged since 2011. METHODS: The Pediatrix Medical Group Clinical Data
      Warehouse was queried for the years 2009-2013 to describe first exposure iNO use
      among all admitted neonates stratified by gestational age. RESULTS: Between 2009
      and 2013, the rate of iNO utilization in 23- to 29-week neonates increased from
      5.03% to 6.19%, a relative increase of 23% (confidence interval: 8%-40%; P =
      .003). Of all neonates who received iNO therapy in 2013, nearly half were <34
      weeks' gestation, with these infants accounting for more than half of all first
      exposure iNO days each year of the study period. CONCLUSIONS: The rates of off
      label iNO use in preterm infants continue to rise despite evidence revealing no
      clear benefit in this population. This pattern of iNO prescription is not benign
      and comes with economic consequences.

PMID- 25755238
TI  - An adoptive parental perspective on personal genomic screening.

PMID- 25755239
TI  - Inhaled nitric oxide for the preterm infant: evidence versus practice.

PMID- 25755240
TI  - Etiology of childhood bacteremia and timely antibiotics administration in the
      emergency department.
AB  - BACKGROUND: Bacteremia is now an uncommon presentation to the children's
      emergency department (ED) but is associated with significant morbidity and
      mortality. Its evolving etiology may affect the ability of clinicians to initiate
      timely, appropriate antimicrobial therapy. METHODS: A retrospective time series
      analysis of bacteremia was conducted in the Alder Hey Children's Hospital ED
      between 2001 and 2011. Data on significant comorbidities, time to empirical
      therapy, and antibiotic susceptibility were recorded. RESULTS: A total of 575
      clinical episodes were identified, and Streptococcus pneumoniae (n = 109),
      Neisseria meningitidis (n = 96), and Staphylococcus aureus (n = 89) were commonly
      isolated. The rate of bacteremia was 1.42 per 1000 ED attendances (95% confidence
      interval: 1.31-1.53). There was an annual reduction of 10.6% (6.6%-14.5%) in
      vaccine-preventable infections, and an annual increase of 6.7% (1.2%-12.5%) in
      Gram-negative infections. The pneumococcal conjugate vaccine was associated with
      a 49% (32%-74%) reduction in pneumococcal bacteremia. The rate of health care
      associated bacteremia increased from 0.17 to 0.43 per 1000 ED attendances (P =
      .002). Susceptibility to empirical antibiotics was reduced (96.3%-82.6%; P <
      .001). Health care-associated bacteremia was associated with an increased length
      of stay of 3.9 days (95% confidence interval: 2.3-5.8). Median time to
      antibiotics was 184 minutes (interquartile range: 63-331) and 57 (interquartile
      range: 27-97) minutes longer in Gram-negative bacteremia than in vaccine
      preventable bacteremia. CONCLUSIONS: Changes in the etiology of pediatric
      bacteremia have implications for prompt, appropriate empirical treatment.
      Increasingly, pediatric bacteremia in the ED is health care associated, which
      increases length of inpatient stay. Prompt, effective antimicrobial
      administration requires new tools to improve recognition, in addition to
      continued etiological surveillance.

PMID- 25755241
TI  - Cardiac biomarkers and acute kidney injury after cardiac surgery.
AB  - OBJECTIVES: To examine the relationship of cardiac biomarkers with postoperative
      acute kidney injury (AKI) among pediatric patients undergoing cardiac surgery.
      METHODS: Data from TRIBE-AKI, a prospective study of children undergoing cardiac
      surgery, were used to examine the association of cardiac biomarkers (N-type pro-B
      type natriuretic peptide, creatine kinase-MB [CK-MB], heart-type fatty acid
      binding protein [h-FABP], and troponins I and T) with the development of
      postoperative AKI. Cardiac biomarkers were collected before and 0 to 6 hours
      after surgery. AKI was defined as a >= 50% or 0.3 mg/dL increase in serum
      creatinine, within 7 days of surgery. RESULTS: Of the 106 patients included in
      this study, 55 (52%) developed AKI after cardiac surgery. Patients who developed
      AKI had higher median levels of pre- and postoperative cardiac biomarkers
      compared with patients without AKI (all P < .01). Preoperatively, higher levels
      of CK-MB and h-FABP were associated with increased odds of developing AKI (CK-MB:
      adjusted odds ratio 4.58, 95% confidence interval [CI] 1.56-13.41; h-FABP:
      adjusted odds ratio 2.76, 95% CI 1.27-6.03). When combined with clinical models,
      both preoperative CK-MB and h-FABP provided good discrimination (area under the
      curve 0.77, 95% CI 0.68-0.87, and 0.78, 95% CI 0.68-0.87, respectively) and
      improved reclassification indices. Cardiac biomarkers collected postoperatively
      did not significantly improve the prediction of AKI beyond clinical models.
      CONCLUSIONS: Preoperative CK-MB and h-FABP are associated with increased risk of
      postoperative AKI and provide good discrimination of patients who develop AKI.
      These biomarkers may be useful for risk stratifying patients undergoing cardiac
      surgery.

PMID- 25755243
TI  - Retinal microvasculature and cardiovascular health in childhood.
AB  - BACKGROUND AND OBJECTIVE: Alterations in retinal microvasculature are associated
      with increased risk of cardiovascular disease. We examined the associations of
      retinal vessel caliber with cardiovascular markers in school-age children.
      METHODS: Among 4007 school-age children (median age of 6.0 years), we measured
      cardiovascular markers and retinal vessel calibers from digitized retinal
      photographs. RESULTS: Narrower retinal arteriolar caliber was associated with
      higher systolic and diastolic blood pressure (-0.20 SD score [SDS] [95%
      confidence interval (CI) -0.24 to -0.18] and -0.14 SDS [-0.17 to -0.11],
      respectively, per SDS increase in retinal arteriolar caliber), mean arterial
      pressure, and pulse pressure, but not with carotid-femoral pulse wave velocity,
      heart rate, cardiac output, or left ventricular mass. A wider retinal venular
      caliber was associated with lower systolic blood pressure, mean arterial
      pressure, and pulse pressure and higher carotid-femoral pulse wave velocity
      (carotid-femoral pulse wave velocity difference = 0.04 SDS [95% CI 0.01 to 0.07]
      per SDS increase in retinal venular caliber). Both narrower retinal arteriolar
      and venular calibers were associated with higher risk of hypertension at the age
      of 6 years, with the strongest association for retinal arteriolar caliber (odds
      ratio 1.35 [95% CI 1.21 to 1.45] per SDS decrease in arteriolar caliber).
      Adjustment for parental and infant sociodemographic factors did not influence the
      observed associations. CONCLUSIONS: Both retinal arteriolar and venular calibers
      are associated with blood pressure in school-age children, whereas retinal
      venular caliber is associated with carotid-femoral pulse wave velocity.
      Microvascular adaptations in childhood might influence cardiovascular health and
      disease from childhood onward.

PMID- 25755242
TI  - Comorbidity of physical and mental disorders in the neurodevelopmental genomics
      cohort study.
AB  - OBJECTIVES: To examine patterns of associations between a broad range of mental
      and physical conditions by using a large, systematically obtained pediatric
      registry. METHODS: The sample included 9014 youth ages 8 to 21 years (4349 males
      and 4665 females; 3585 aged <13 years, 3678 aged 13 to 18 years, and 1751 aged 19
      to 21 years) from the Philadelphia Neurodevelopmental Cohort identified through
      pediatric clinics at the Children's Hospital of Philadelphia health care network
      by the Center for Applied Genomics. Measures were as follows: physical condition
      based on electronic medical records and interview data on 42 physical conditions
      of 14 organ systems/specialties and mental disorders based on an abbreviated
      version of the structured Kiddie-Schedule for Affective Disorders and
      Schizophrenia psychiatric diagnostic interview. RESULTS: There was a direct
      association between the severity of the physical condition and most classes of
      mental disorders, as well as with functional impairment. Models adjusted for
      sociodemographic correlates, other physical and mental disorders, and false
      discovery and revealed broad patterns of associations between neurodevelopmental
      disorders with behavior disorders (odds ratio [OR]: 1.5; 95% confidence interval
      [CI]: 1.3-1.8; P < .004) and attention-deficit/hyperactivity disorder (OR: 3.1;
      95% CI: 2.7-3.6; P < .0001), and neurologic/central nervous system conditions
      (OR: 1.3; 95% CI: 1.1-1.9; P < .05) with mood disorders and attention
      deficit/hyperactivity disorder (OR: 1.3; 95% CI: 1.1-1.5; P < .001), and
      autoimmune/inflammatory conditions with mood disorders (OR: 1.4; 95% CI: 1.1-1.8,
      P < .05). CONCLUSIONS: Findings show the strong overlap between physical and
      mental conditions and their impact on severity and functional impairment in
      youth. Specific patterns of comorbidity have important implications for etiology.
      Prospective tracking of cross-disorder morbidity will be important to establish
      more effective mechanisms for prevention and intervention.

PMID- 25755245
TI  - Antidepressant use during pregnancy and asthma in the offspring.
AB  - BACKGROUND AND OBJECTIVES: It has been suggested that maternal depression during
      pregnancy is associated with asthma in the offspring, but the role of medical
      treatment of depression is not known. Our goal was to examine whether prenatal
      antidepressant use increases the risk of asthma in the offspring. METHODS: A
      cohort study was performed among all live singletons born in Denmark between 1996
      and 2007. Mothers who had a diagnosis of depressive disorder and/or who used
      antidepressants 1 year before or during the index pregnancy were identified.
      Using a Cox proportional hazards regression model, we estimated the hazard ratio
      (HR) for asthma in the offspring after antidepressant use during pregnancy.
      RESULTS: Of the 733,685 children identified, 84,683 had a diagnosis of asthma. A
      total of 21,371 children were exposed to prenatal maternal depression (ie, a
      diagnosis of depressive disorder or use of antidepressants 1 year before or
      during pregnancy). Prenatal maternal depression was associated with childhood
      asthma (HR: 1.25 [95% confidence interval (CI): 1.20-1.30]). Overall, 8895
      children were exposed to antidepressants in utero. Compared with children born to
      mothers with prenatal depression and no antidepressant use during pregnancy, the
      HR for asthma after any antidepressant use during pregnancy was 1.00 (95% CI:
      0.93-1.08). HRs after use of selective serotonin reuptake inhibitors only, newer
      antidepressants only, and older antidepressants only were 0.95 (95% CI: 0.88
      1.03), 1.11 (95% CI: 0.89-1.39), and 1.26 (95% CI: 1.02-1.55), respectively.
      CONCLUSIONS: Antidepressant use during pregnancy generally did not increase the
      risk of asthma. Only use of older antidepressants was associated with an
      increased risk of asthma.

PMID- 25755244
TI  - Using quality improvement to reduce continuous pulse oximetry use in children
      with wheezing.
AB  - BACKGROUND AND OBJECTIVES: Clinicians commonly use continuous pulse oximetry
      (CPOx) for hospitalized children with respiratory illnesses. The Choosing Wisely
      initiative recommended discontinuing CPOx for children on room air. We used
      quality improvement methods to reduce time on CPOx in patients with wheezing.
      METHODS: Our project took place on 1 unit of a children's hospital. We developed
      consensus-based criteria for CPOx discontinuation. Interventions included
      education, a checklist used during nurse handoff, and discontinuation criteria
      incorporated into order sets. We collected data on a second unit where we did not
      actively intervene to assess for secular trends and negative consequences of
      shorter monitoring. We followed time until medically ready, ICU transfers,
      hospital revisits, and medical emergency team calls on both units. We tracked the
      impact of interventions by using run charts and statistical process control
      charts. RESULTS: Median time per week on CPOx after meeting goals decreased from
      10.7 hours to 3.1 hours on the intervention unit. Median time per week on CPOx on
      the control unit decreased from 11.5 hours to 6.9 hours. There was no decrease in
      time until medically ready on either unit. The percentage of patients needing
      transfer, revisit, or medical emergency team call was similar on both units.
      CONCLUSIONS: With interventions focused on clarity and awareness of CPOx
      discontinuation criteria, we decreased time on CPOx; however, we saw no impact on
      time until medically ready. We expect that other centers could use analogous
      methods to standardize and reduce oxygen monitoring to meet Choosing Wisely
      recommendations.

PMID- 25755246
TI  - Folic acid levels in some food staples in Ireland are on the decline:
      implications for passive folic acid intakes?
AB  - BACKGROUND: Neural tube defects are largely preventable by the maternal
      periconceptual consumption of folic acid. The aim of this study was to examine
      the levels of synthetic folic acid in foods and the range of food stuffs with
      added folic acid available to consumers in Ireland at the current time. METHODS:
      Three audits of fortified foods available in supermarkets in the Republic of
      Ireland were conducted. Researchers visited supermarkets and obtained folic acid
      levels from nutrition labels in 2004, 2008 and 2013/4. Levels were compared using
      MS Excel. RESULTS: The profile of foods fortified with folic acid in 2013/4 has
      changed since 2004. The percentage of foods fortified with folic acid has
      decreased as has the level of added folic acid in some food staples, such as
      fat/dairy spreads. CONCLUSION: Bread, milk and spreads no longer contain as much
      folic acid as previously (2004 and 2008). This may contribute to a decrease in
      folate intake and therefore may contribute to an increase in NTD rates. Research
      on current blood concentrations of folate status markers is now warranted.

PMID- 25755247
TI  - High incidence of aplastic anemia is linked with lower socioeconomic status of
      Indian population.
AB  - BACKGROUND: The incidence of aplastic anemia (AA) is common in Asia than in
      western countries. METHODS: In a case-control study conducted at a tertiary care
      hematology center in northern India, 102 patients of AA and 201 controls of other
      blood disorders (OBD) were included. Sociodemographic data and exposure to drugs,
      toxins and radiation were collected from the study population using a standard
      questionnaire. Socioeconomic status (SES) was classified based on a calculated
      standard of living (SL) score. Univariate and multivariate analyses were carried
      out to delineate the factors associated with incidence of AA. RESULTS: Patients
      with AA were significantly younger than those in control groups (mean age 27.5 +/
      12.3 years, P < 0.01). The mean SL score was significantly lower in AA group
      (26.76 +/- 12.88, P < 0.01) than in the controls. The mean monthly family income
      was significantly lower in AA group than in the controls (83.3% with monthly
      income <8000 INR, P < 0.01). On univariate analysis, AA group with lower SL score
      had >3 times higher odds of having the disease (odds ratio 3.41, 95% confidence
      interval 1.72-6.79, P < 0.0001) compared with the controls. On multivariate
      analysis, young age and low SES were found to be significantly associated with
      AA. CONCLUSIONS: Lower SES is associated with higher incidence of AA in Indian
      population.

PMID- 25755248
TI  - Analysis of hospital admissions due to accidental non-fire-related carbon
      monoxide poisoning in England, between 2001 and 2010.
AB  - BACKGROUND: Accidental non-fire-related (ANFR) carbon monoxide (CO) poisoning is
      a cause of fatalities and hospital admissions. This is the first study that
      describes the characteristics of ANFR CO hospital admissions in England. METHODS:
      Hospital Episode Statistics (HES) inpatient data for England between 2001 and
      2010 were used. ANFR CO poisoning admissions were defined as any mention of ICD
      10 code T58: toxic effect of CO and X47: accidental poisoning by gases or
      vapours, excluding ICD-10 codes potentially related to fires (X00-X09, T20-T32
      and Y26). RESULTS: There were 2463 ANFR CO admissions over the 10-year period
      (annual rate: 0.49/100 000); these comprised just under half (48.7%) of all non
      fire-related (accidental and non-accidental) CO admissions. There was seasonal
      variability, with more admissions in colder winter months. Higher admission rates
      were observed in the north of England. Just over half (53%) of ANFR admissions
      were male, and the highest rates of ANFR admissions were in those aged >80 years.
      CONCLUSION: The burden of ANFR CO poisoning is preventable. The results of this
      study suggest an appreciable burden of CO and highlight differences that may aid
      targeting of public health interventions.

PMID- 25755251
TI  - The efficacy of fat emulsion and normal saline for bile leakage tests during
      hepatic resection: A randomized trial.
AB  - OBJECTIVE: A randomized controlled trial to evaluate the use of fat emulsion and
      normal saline for bile leakage tests during hepatic resection. METHODS: Patients
      were randomized to undergo intraoperative bile leakage tests with saline then fat
      emulsion (Group A), or fat emulsion then saline (Group B). All patients received
      both tests. RESULTS: In group A (n = 64), saline revealed 53 leakage points in 27
      patients, and fat emulsion revealed 42 additional points in a further nine
      patients. In group B (n = 64), fat emulsion revealed 87 leakage points in 37
      patients, and saline revealed three additional points in three patients. There
      were no significant between-group differences in the number of leakage points
      detected by the first test, total number of leakage points or postoperative
      complications. Significantly more leakage points were detected by the second test
      in Group A (fat emulsion) than in Group B (saline). CONCLUSIONS: Fat emulsion
      then saline identifies more leakage points after the first test than saline then
      fat emulsion. There is no difference in the total number of leakage points
      detected, regardless of which method is used first.

PMID- 25755249
TI  - An LXR-NCOA5 gene regulatory complex directs inflammatory crosstalk-dependent
      repression of macrophage cholesterol efflux.
AB  - LXR-cofactor complexes activate the gene expression program responsible for
      cholesterol efflux in macrophages. Inflammation antagonizes this program,
      resulting in foam cell formation and atherosclerosis; however, the molecular
      mechanisms underlying this antagonism remain to be fully elucidated. We use
      promoter enrichment-quantitative mass spectrometry (PE-QMS) to characterize the
      composition of gene regulatory complexes assembled at the promoter of the lipid
      transporter Abca1 following downregulation of its expression. We identify a
      subset of proteins that show LXR ligand- and binding-dependent association with
      the Abca1 promoter and demonstrate they differentially control Abca1 expression.
      We determine that NCOA5 is linked to inflammatory Toll-like receptor (TLR)
      signaling and establish that NCOA5 functions as an LXR corepressor to attenuate
      Abca1 expression. Importantly, TLR3-LXR signal crosstalk promotes recruitment of
      NCOA5 to the Abca1 promoter together with loss of RNA polymerase II and reduced
      cholesterol efflux. Together, these data significantly expand our knowledge of
      regulatory inputs impinging on the Abca1 promoter and indicate a central role for
      NCOA5 in mediating crosstalk between pro-inflammatory and anti-inflammatory
      pathways that results in repression of macrophage cholesterol efflux. 

PMID- 25755250
TI  - SIRT3-dependent GOT2 acetylation status affects the malate-aspartate NADH shuttle
      activity and pancreatic tumor growth.
AB  - The malate-aspartate shuttle is indispensable for the net transfer of cytosolic
      NADH into mitochondria to maintain a high rate of glycolysis and to support rapid
      tumor cell growth. The malate-aspartate shuttle is operated by two pairs of
      enzymes that localize to the mitochondria and cytoplasm, glutamate oxaloacetate
      transaminases (GOT), and malate dehydrogenases (MDH). Here, we show that
      mitochondrial GOT2 is acetylated and that deacetylation depends on mitochondrial
      SIRT3. We have identified that acetylation occurs at three lysine residues, K159,
      K185, and K404 (3K), and enhances the association between GOT2 and MDH2. The GOT2
      acetylation at these three residues promotes the net transfer of cytosolic NADH
      into mitochondria and changes the mitochondrial NADH/NAD(+) redox state to
      support ATP production. Additionally, GOT2 3K acetylation stimulates NADPH
      production to suppress ROS and to protect cells from oxidative damage. Moreover,
      GOT2 3K acetylation promotes pancreatic cell proliferation and tumor growth in
      vivo. Finally, we show that GOT2 K159 acetylation is increased in human
      pancreatic tumors, which correlates with reduced SIRT3 expression. Our study
      uncovers a previously unknown mechanism by which GOT2 acetylation stimulates the
      malate-aspartate NADH shuttle activity and oxidative protection. 

PMID- 25755252
TI  - LACCASE5 is required for lignification of the Brachypodium distachyon Culm.
AB  - The oxidation of monolignols is a required step for lignin polymerization and
      deposition in cell walls. In dicots, both peroxidases and laccases are known to
      participate in this process. Here, we provide evidence that laccases are also
      involved in the lignification of Brachypodium distachyon, a model plant for
      temperate grasses. Transcript quantification data as well as in situ and
      immunolocalization experiments demonstrated that at least two laccases (LACCASE5
      and LACCASE6) are present in lignifying tissues. A mutant with a misspliced
      LACCASE5 messenger RNA was identified in a targeting-induced local lesion in
      genome mutant collection. This mutant shows 10% decreased Klason lignin content
      and modification of the syringyl-to-guaiacyl units ratio. The amount of ferulic
      acid units ester linked to the mutant cell walls is increased by 40% when
      compared with control plants, while the amount of ferulic acid units ether linked
      to lignins is decreased. In addition, the mutant shows a higher saccharification
      efficiency. These results provide clear evidence that laccases are required for
      B. distachyon lignification and are promising targets to alleviate the
      recalcitrance of grass lignocelluloses.

PMID- 25755253
TI  - Responses of Arabidopsis and wheat to rising CO2 depend on nitrogen source and
      nighttime CO2 levels.
AB  - A major contributor to the global carbon cycle is plant respiration. Elevated
      atmospheric CO2 concentrations may either accelerate or decelerate plant
      respiration for reasons that have been uncertain. We recently established that
      elevated CO2 during the daytime decreases plant mitochondrial respiration in the
      light and protein concentration because CO2 slows the daytime conversion of
      nitrate (NO3 (-)) into protein. This derives in part from the inhibitory effect
      of CO2 on photorespiration and the dependence of shoot NO3 (-) assimilation on
      photorespiration. Elevated CO2 also inhibits the translocation of nitrite into
      the chloroplast, a response that influences shoot NO3 (-) assimilation during
      both day and night. Here, we exposed Arabidopsis (Arabidopsis thaliana) and wheat
      (Triticum aestivum) plants to daytime or nighttime elevated CO2 and supplied them
      with NO3 (-) or ammonium as a sole nitrogen (N) source. Six independent measures
      (plant biomass, shoot NO3 (-), shoot organic N, (15)N isotope fractionation,
      (15)NO3 (-) assimilation, and the ratio of shoot CO2 evolution to O2 consumption)
      indicated that elevated CO2 at night slowed NO3 (-) assimilation and thus
      decreased dark respiration in the plants reliant on NO3 (-). These results
      provide a straightforward explanation for the diverse responses of plants to
      elevated CO2 at night and suggest that soil N source will have an increasing
      influence on the capacity of plants to mitigate human greenhouse gas emissions.

PMID- 25755254
TI  - Carbon-ion beams induce production of an immune mediator protein, high mobility
      group box 1, at levels comparable with X-ray irradiation.
AB  - X-ray radiotherapy activates tumor antigen-specific T-cell responses, and
      increases in the serum levels of high mobility group box 1 (HMGB1) induced by X
      ray irradiation play a pivotal role in activating anti-tumor immunity. Here, we
      examined whether carbon-ion beams, as well as X-rays, can induce HMGB1 release
      from human cancer cell lines. The study examined five human cancer cell lines:
      TE2, KYSE70, A549, NCI-H460 and WiDr. The proportion of cells surviving X- or
      carbon-ion beam irradiation was assessed in a clonogenic assay. The D10, the dose
      at which 10% of cells survive, was calculated using a linear-quadratic model.
      HMGB1 levels in the culture supernatants were assessed by an ELISA. The D10 dose
      for X-rays in TE2, KYSE70, A549, NCI-H460 and WiDr cells was 2.1, 6.7, 8.0, 4.8
      and 7.1 Gy, respectively, whereas that for carbon-ion beams was 0.9, 2.5, 2.7,
      1.8 and 3.5 Gy, respectively. X-rays and carbon-ion beams significantly increased
      HMGB1 levels in the culture supernatants of A549, NCI-H460 and WiDr cells at 72 h
      post-irradiation with a D10 dose. Furthermore, irradiation with X-rays or carbon
      ion beams significantly increased HMGB1 levels in the culture supernatants of all
      five cell lines at 96 h post-irradiation. There was no significant difference in
      the amount of HMGB1 induced by X-rays and carbon-ion beams at any time-point
      (except at 96 h for NCI-H460 cells); thus we conclude that comparable levels of
      HMGB1 were detected after irradiation with iso-survival doses of X-rays and
      carbon-ion beams. 

PMID- 25755255
TI  - Comparison of adverse effects of proton and X-ray chemoradiotherapy for
      esophageal cancer using an adaptive dose-volume histogram analysis.
AB  - Cardiopulmonary late toxicity is of concern in concurrent chemoradiotherapy
      (CCRT) for esophageal cancer. The aim of this study was to examine the benefit of
      proton beam therapy (PBT) using clinical data and adaptive dose-volume histogram
      (DVH) analysis. The subjects were 44 patients with esophageal cancer who
      underwent definitive CCRT using X-rays (n = 19) or protons (n = 25). Experimental
      recalculation using protons was performed for the patient actually treated with X
      rays, and vice versa. Target coverage and dose constraints of normal tissues were
      conserved. Lung V5-V20, mean lung dose (MLD), and heart V30-V50 were compared for
      risk organ doses between experimental plans and actual treatment plans. Potential
      toxicity was estimated using protons in patients actually treated with X-rays,
      and vice versa. Pulmonary events of Grade >=2 occurred in 8/44 cases (18%), and
      cardiac events were seen in 11 cases (25%). Risk organ doses in patients with
      events of Grade >=2 were significantly higher than for those with events of Grade
      <=1. Risk organ doses were lower in proton plans compared with X-ray plans. All
      patients suffering toxicity who were treated with X-rays (n = 13) had reduced
      predicted doses in lung and heart using protons, while doses in all patients
      treated with protons (n = 24) with toxicity of Grade <=1 had worsened predicted
      toxicity with X-rays. Analysis of normal tissue complication probability showed a
      potential reduction in toxicity by using proton beams. Irradiation dose, volume
      and adverse effects on the heart and lung can be reduced using protons. Thus, PBT
      is a promising treatment modality for the management of esophageal cancer. 

PMID- 25755257
TI  - Lindau in the 21st Century: more women, more dialog, more passion: An interview
      with Countess Bettina Bernadotte and Wolfgang Schurer from the Lindau Nobel
      Laureate Meetings.

PMID- 25755256
TI  - The alanine-serine-cysteine-1 (Asc-1) transporter controls glycine levels in the
      brain and is required for glycinergic inhibitory transmission.
AB  - Asc-1 (SLC7A10) is an amino acid transporter whose deletion causes neurological
      abnormalities and early postnatal death in mice. Using metabolomics and
      behavioral and electrophysiological methods, we demonstrate that Asc-1 knockout
      mice display a marked decrease in glycine levels in the brain and spinal cord
      along with impairment of glycinergic inhibitory transmission, and a hyperekplexia
      like phenotype that is rescued by replenishing brain glycine. Asc-1 works as a
      glycine and L-serine transporter, and its transport activity is required for the
      subsequent conversion of L-serine into glycine in vivo. Asc-1 is a novel
      regulator of glycine metabolism and a candidate for hyperekplexia disorders.

PMID- 25755258
TI  - Non-Pharmacological Interventions for ADHD in School Settings: An Overarching
      Synthesis of Systematic Reviews.
AB  - OBJECTIVE: This overarching synthesis brings together the findings of four
      systematic reviews including 138 studies focused on non-pharmacological
      interventions for ADHD used in school settings. These reviews considered the
      effectiveness of school-based interventions for ADHD, attitudes toward and
      experience of school-based interventions for ADHD, and the experience of ADHD in
      school settings. METHOD: We developed novel methods to compare the findings
      across these reviews inductively and deductively. RESULTS: Key contextual issues
      that may influence the effectiveness and implementation of interventions include
      the relationships that pupils with ADHD have with their teachers and peers, the
      attributions individuals make about the etiology of ADHD, and stigma related to
      ADHD or intervention attendance. CONCLUSION: Although we found some positive
      effects for some outcomes and intervention categories, heterogeneity in effect
      size estimates and research evidence suggests a range of diverse contextual
      factors potentially moderate the implementation and effectiveness of school-based
      interventions for ADHD.

PMID- 25755259
TI  - Parental Involvement in CBT for Anxiety-Disordered Youth Revisited: Family CBT
      Outperforms Child CBT in the Long Term for Children With Comorbid ADHD Symptoms.
AB  - OBJECTIVE: The objective of this study was to examine the efficacy of child
      cognitive-behavioral therapy (CCBT) versus family CBT (FCBT) in anxiety
      disordered youth with high and low comorbid ADHD symptoms. METHOD: Youth with
      anxiety disorders ( n = 123, aged 8-18) were classified in four groups according
      to (a) the type of CBT received (child vs. family) and (b) their comorbid ADHD
      symptoms, measured with the Child Behavior Checklist (CBCL) Attention Problems
      syndrome scale level (normal vs. [sub]clinical). Severity of anxiety disorders
      was assessed with Anxiety Disorders Interview Schedule-Child and Parent (ADIS
      C/P) version and anxiety symptoms via a 71-item anxiety symptom questionnaire,
      the Screen for Child Anxiety and Related Emotional Disorders (SCARED-71), before
      and after CBT, and at 3 months and 1-year follow-ups. RESULTS: Based on the
      severity of anxiety disorders, children with high ADHD symptoms profit more from
      FCBT than CCBT in the long term. For children low on ADHD symptoms, and for
      anxiety symptoms and attention problems, no differences between CCBT and FCBT
      occurred. CONCLUSION: Family involvement seems a valuable addition to CBT for
      children with comorbid anxiety and ADHD symptoms.

PMID- 25755261
TI  - Solar electricity supply isolines of generation capacity and storage.
AB  - The recent sharp drop in the cost of photovoltaic (PV) electricity generation
      accompanied by globally rapidly increasing investment in PV plants calls for new
      planning and management tools for large-scale distributed solar networks. Of
      major importance are methods to overcome intermittency of solar electricity,
      i.e., to provide dispatchable electricity at minimal costs. We find that pairs of
      electricity generation capacity G and storage S that give dispatchable
      electricity and are minimal with respect to S for a given G exhibit a smooth
      relationship of mutual substitutability between G and S. These isolines between G
      and S support the solving of several tasks, including the optimal sizing of
      generation capacity and storage, optimal siting of solar parks, optimal
      connections of solar parks across time zones for minimizing intermittency, and
      management of storage in situations of far below average insolation to provide
      dispatchable electricity. G-S isolines allow determining the cost-optimal pair
      (G,S) as a function of the cost ratio of G and S. G-S isolines provide a method
      for evaluating the effect of geographic spread and time zone coverage on costs of
      solar electricity. 

PMID- 25755260
TI  - Chromatin proteomic profiling reveals novel proteins associated with histone
      marked genomic regions.
AB  - More than a thousand proteins are thought to contribute to mammalian chromatin
      and its regulation, but our understanding of the genomic occupancy and function
      of most of these proteins is limited. Here we describe an approach, which we call
      "chromatin proteomic profiling," to identify proteins associated with genomic
      regions marked by specifically modified histones. We used ChIP-MS to identify
      proteins associated with genomic regions marked by histones modified at specific
      lysine residues, including H3K27ac, H3K4me3, H3K79me2, H3K36me3, H3K9me3, and
      H4K20me3, in ES cells. We identified 332 known and 114 novel proteins associated
      with these histone-marked genomic segments. Many of the novel candidates have
      been implicated in various diseases, and their chromatin association may provide
      clues to disease mechanisms. More than 100 histone modifications have been
      described, so similar chromatin proteomic profiling studies should prove to be
      valuable for identifying many additional chromatin-associated proteins in a broad
      spectrum of cell types. 

PMID- 25755262
TI  - Visual Turing test for computer vision systems.
AB  - Today, computer vision systems are tested by their accuracy in detecting and
      localizing instances of objects. As an alternative, and motivated by the ability
      of humans to provide far richer descriptions and even tell a story about an
      image, we construct a "visual Turing test": an operator-assisted device that
      produces a stochastic sequence of binary questions from a given test image. The
      query engine proposes a question; the operator either provides the correct answer
      or rejects the question as ambiguous; the engine proposes the next question
      ("just-in-time truthing"). The test is then administered to the computer-vision
      system, one question at a time. After the system's answer is recorded, the system
      is provided the correct answer and the next question. Parsing is trivial and
      deterministic; the system being tested requires no natural language processing.
      The query engine employs statistical constraints, learned from a training set, to
      produce questions with essentially unpredictable answers-the answer to a
      question, given the history of questions and their correct answers, is nearly
      equally likely to be positive or negative. In this sense, the test is only about
      vision. The system is designed to produce streams of questions that follow
      natural story lines, from the instantiation of a unique object, through an
      exploration of its properties, and on to its relationships with other uniquely
      instantiated objects. 

PMID- 25755264
TI  - A High-Throughput Mass Spectrometry Assay Coupled with Redox Activity Testing
      Reduces Artifacts and False Positives in Lysine Demethylase Screening.
AB  - Demethylation of histones by lysine demethylases (KDMs) plays a critical role in
      controlling gene transcription. Aberrant demethylation may play a causal role in
      diseases such as cancer. Despite the biological significance of these enzymes,
      there are limited assay technologies for study of KDMs and few quality chemical
      probes available to interrogate their biology. In this report, we demonstrate the
      utility of self-assembled monolayer desorption/ionization (SAMDI) mass
      spectrometry for the investigation of quantitative KDM enzyme kinetics and for
      high-throughput screening for KDM inhibitors. SAMDI can be performed in 384-well
      format and rapidly allows reaction components to be purified prior to injection
      into a mass spectrometer, without a throughput-limiting liquid chromatography
      step. We developed sensitive and robust assays for KDM1A (LSD1, AOF2) and KDM4C
      (JMJD2C, GASC1) and screened 13,824 compounds against each enzyme. Hits were
      rapidly triaged using a redox assay to identify compounds that interfered with
      the catalytic oxidation chemistry used by the KDMs for the demethylation
      reaction. We find that overall this high-throughput mass spectrometry platform
      coupled with the elimination of redox active compounds leads to a hit rate that
      is manageable for follow-up work. 

PMID- 25755263
TI  - Genome-wide ancestry of 17th-century enslaved Africans from the Caribbean.
AB  - Between 1500 and 1850, more than 12 million enslaved Africans were transported to
      the New World. The vast majority were shipped from West and West-Central Africa,
      but their precise origins are largely unknown. We used genome-wide ancient DNA
      analyses to investigate the genetic origins of three enslaved Africans whose
      remains were recovered on the Caribbean island of Saint Martin. We trace their
      origins to distinct subcontinental source populations within Africa, including
      Bantu-speaking groups from northern Cameroon and non-Bantu speakers living in
      present-day Nigeria and Ghana. To our knowledge, these findings provide the first
      direct evidence for the ethnic origins of enslaved Africans, at a time for which
      historical records are scarce, and demonstrate that genomic data provide another
      type of record that can shed new light on long-standing historical questions. 

PMID- 25755265
TI  - A High-Throughput Enzyme-Coupled Assay for SAMHD1 dNTPase.
AB  - Sterile alpha motif and histidine-aspartate domain-containing protein 1 (SAMHD1)
      is a recently discovered enzyme that plays a central role in nucleotide
      metabolism and innate immunity. SAMHD1 has deoxyribonucleoside triphosphate
      (dNTP) triphosphohydrolase activity that depletes the dNTP substrates required
      for DNA synthesis in cells. The involvement of SAMHD1 in biological processes as
      varied as viral restriction, endogenous retroelement control, cancer, and
      modulation of anticancer/antiviral nucleoside drug efficacy makes it a valuable
      target for the development of small-molecule inhibitors. We report a high
      throughput colorimetric assay for SAMHD1 dNTP hydrolase activity that takes
      advantage of Escherichia coli inorganic pyrophosphatase to convert PPPi to 3 Pi.
      The assay was validated by screening a library of 2653 clinically used compounds.
      Fifteen primary hits were obtained (0.57% hit rate); 80% of these were confirmed
      in a direct secondary assay for dNTP hydrolysis. The zinc salt of the antibiotic
      cephalosporin C was a potent inhibitor of SAMHD1 with an IC50 of 1.1 +/- 0.1 uM,
      and this inhibition was largely attributable to the presence of zinc. The assay
      also screened a targeted library of nucleosides and their analogs, revealing that
      the antiviral drug acycloguanosine (acyclovir) is an inhibitor possessing
      excellent properties for future fragment-based drug development efforts. 

PMID- 25755266
TI  - Reducing stress and burnout in junior doctors: the impact of debriefing sessions.
AB  - BACKGROUND: Internship and residency are difficult times with novice
      practitioners facing new challenges and stressors. Junior doctors may experience
      burnout, a syndrome that encompasses three dimensions: emotional exhaustion,
      depersonalisation and reduced personal accomplishment. While there is some
      existing literature on the prevalence of burnout in junior doctors, there are few
      studies on interventional strategies. AIMS: This study aimed to examine the
      prevalence of burnout in a cohort of junior doctors and whether debriefing
      sessions reduced levels of burnout. METHODS: A prospective randomised controlled
      study of a convenience sample of postgraduate year 1 doctors in a single hospital
      was undertaken during a rotation term in 2011. All participants completed a
      questionnaire using a validated tool, the Maslach Burnout Inventory, to determine
      the prevalence of burnout. They were then randomly assigned to a group who were
      to receive four debriefing sessions over 2 months, or, to the control group, who
      had no debriefing sessions. Quantitative and qualitative analyses were conducted.
      RESULTS: Thirty-one postgraduate year 1 doctors participated in the study, with
      13 being assigned to the group receiving debriefing sessions and 18 assigned to
      the control group. At baseline, 21/31 (68%) participants displayed evidence of
      burnout in at least one domain as measured by the Maslach Burnout Inventory.
      Burnout was significantly higher in women. There was no significant difference in
      burnout scores with debriefing. The intervention was well received with 11/18
      (61%) suggesting they would recommend the strategy to future junior doctors and
      16/18 (89%) found that the sessions were a source of emotional and social
      support. CONCLUSIONS: Burnout is prevalent among postgraduate year 1 doctors, and
      they value the emotional and social support from attending debriefing sessions. A
      larger study is required to determine if debriefing can reduce the incidence of
      burnout in junior doctors.

PMID- 25755267
TI  - Female perineal injuries in children and adolescents presenting to a paediatric
      emergency department.
AB  - This retrospective case series determined documentation quality and likelihood of
      safeguarding issues in girls  aged 0-15 years with perineal and genital injuries
      presenting to a paediatric emergency department (ED). During the period between
      2002 and 2010, cases were identified and clinical information was recorded. Cases
      were cross-referenced against the hospital's safeguarding unit's records up to
      2011. In total, 181 case notes were available for review with 76.2% of patients
      discharged home from the ED. Fewer than 50% of case notes contained clear
      anatomical description of the injuries. In 51 (28.2%) cases, child safeguarding
      issues were considered, with specific referrals made to safeguarding services in
      20 of these (11.0%). Only one case involved subsequent child safeguarding
      proceedings. Clear documentation of injury patterns by medical staff was poor,
      but medical and nursing staff should not be anxious about dealing with this
      cohort of patients as they are no different from other incidental injuries
      needing diligent levels of child safeguarding awareness. 

PMID- 25755268
TI  - Lactate level, aetiology and mortality of adult patients in an emergency
      department: a cohort study.
AB  - BACKGROUND: Increased lactate is associated with high mortality among patients
      with suspected infection or trauma in the emergency department (ED), but the
      association with patients with other aetiologies is less well described. The aim
      of this study was to describe the relation between lactate, aetiology and 7-day
      mortality in adult ED patients. METHODS: A retrospective cohort study of all
      adult patients who had a lactate measured within 4 h after arrival to the ED at
      Odense University Hospital between June 2012 and May 2013. The categorisation of
      suspected aetiology was based on discharge diagnoses. RESULTS: 5360 patients were
      included; 51.7% were men, and the median age was 67 years (IQR 50-79). 77.2% had
      low lactate (0-1.9 mmol/L), 16.2% intermediate lactate (2-3.9 mmol/L), and 6.6%
      high lactate (>=4 mmol/L). 7-day mortality was 2.9% (95% CI 2.4% to 3.5%) for
      patients with low lactate, 7.8% (95% CI 6.1% to 9.8%) for patients with
      intermediate lactate, and 23.9% (95% CI 19.6% to 28.8%) for patients with high
      lactate. The association between lactate level and mortality varied across
      different diagnostic groups. Based on Area Under the Curve in receiver operating
      characteristic analysis, lactate level showed to be useful in patients with
      infection (0.78, 95% CI 0.73 to 0.84), trauma (0.78, 95% CI 0.65 to 0.92),
      cardiac diseases (0.83, 95% CI 0.75 to 0.91) and gastrointestinal diseases (0.83,
      95% CI 0.68 to 0.98). Lactate level was not useful in neurological (0.58, 95% CI
      0.50 to 0.67) and respiratory disease (0.64, 95% CI 0.55 to 0.74), and of
      uncertain value in the remaining diagnostic groups. CONCLUSIONS: Among adult ED
      patients, the prognostic value of lactate varies between diagnostic groups.

PMID- 25755269
TI  - The unusual reason of the hand injury: sneeze.

PMID- 25755270
TI  - Age and sex-dependent trends in pulmonary embolism testing and derivation of a
      clinical decision rule for young patients.
AB  - IMPORTANCE: Despite low prevalence of pulmonary embolism (PE) in young adults,
      they are frequently imaged for PE, which involves radiation exposure and
      substantial financial cost. OBJECTIVE: Determine the use and positive proportions
      for PE imaging by age, differences in clinical presentation of PE by age and the
      projected impact of an age-targeted decision rule. DESIGN: Analysis of two
      national population-based datasets: the 2009 Nationwide Emergency Department
      Sample, a 20% sample of US emergency departments (EDs) and the 2003-2006
      Pulmonary Embolism Rule-out Criteria (PERC) dataset, a multisite cohort of ED
      patients with suspected PE from 12 US EDs. RESULTS: Prevalence of PE was 10 times
      lower in young patients (18-35 years) than in older patients (>65 years) (0.06%
      vs 0.60%, p<0.001), but young patients were imaged for PE almost as frequently as
      older patients (2.3% vs 3.2%). This resulted in a lower proportion of positive
      examinations in young adults than older adults (2.3% vs 17.4%, p<0.001 in women;
      4.0% vs 21.4%, p<0.001 in men). Clinical predictors of PE varied by age.
      Tachycardia was a significant predictor of PE in older patients (OR: 1.2-1.9,
      p<0.001), but not young patients. Fever was a significant predictor only in young
      patients (OR: 1.4-7.2, p<0.01). A modification of the previously described PERC
      rule to include age-specific risk factors could reduce PE imaging by 51% in young
      patients, with a missed PE rate of 0.6% in those excluded from imaging.
      CONCLUSIONS AND RELEVANCE: Young patients are frequently imaged for PE and have
      lower positive imaging rates than older patients. After further validation,
      application of our proposed rule for excluding young patients from PE imaging
      could reduce imaging, increase the positive rate of imaging and result in a low
      rate of missed PE among those excluded from imaging.

PMID- 25755271
TI  - Glycosyltransferase-mediated Sweet Modification in Oral Streptococci.
AB  - Bacterial glycosyltransferases play important roles in bacterial fitness and
      virulence. Oral streptococci have evolved diverse strategies to survive and
      thrive in the carbohydrate-rich oral cavity. In this review, we discuss 2
      important biological processes mediated by 2 distinct groups of
      glycosyltransferases in oral streptococci that are important for bacterial
      colonization and virulence. The first process is the glycosylation of highly
      conserved serine-rich repeat adhesins by a series of glycosyltransferases. Using
      Streptococcus parasanguinis as a model, we highlight new features of several
      glycosyltransferases that sequentially modify the serine-rich glycoprotein Fap1.
      Distinct features of a novel glycosyltransferase fold from a domain of unknown
      function 1792 are contrasted with common properties of canonical
      glycosyltransferases. The second biological process we cover is involved in
      building sticky glucan matrix to establish cariogenic biofilms by an important
      opportunistic pathogen Streptococcus mutans through the action of a family of 3
      glucosyltransferases. We focus on discussing the structural feature of this
      family as a glycoside hydrolase family of enzymes. While the 2 processes are
      distinct, they all produce carbohydrate-coated biomolecules, which enable
      bacteria to stick better in the complex oral microbiome. Understanding the making
      of the sweet modification presents a unique opportunity to develop novel
      antiadhesion and antibiofilm strategies to fight infections by oral streptococci
      and beyond. 

PMID- 25755272
TI  - Reducing the search space for causal genetic variants with VASP.
AB  - MOTIVATION: Increasingly, cost-effective high-throughput DNA sequencing
      technologies are being utilized to sequence human pedigrees to elucidate the
      genetic cause of a wide variety of human diseases. While numerous tools exist for
      variant prioritization within a single genome, the ability to concurrently
      analyze variants within pedigrees remains a challenge, especially should there be
      no prior indication of the underlying genetic cause of the disease. Here, we
      present a tool, variant analysis of sequenced pedigrees (VASP), a flexible data
      integration environment capable of producing a summary of pedigree variation,
      providing relevant information such as compound heterozygosity, genome phasing
      and disease inheritance patterns. Designed to aggregate data across a sequenced
      pedigree, VASP allows both powerful filtering and custom prioritization of both
      single nucleotide variants (SNVs) and small indels. Hence, clinical and research
      users with prior knowledge of a disease are able to dramatically reduce the
      variant search space based on a wide variety of custom prioritization criteria.
      AVAILABILITY AND IMPLEMENTATION: Source code available for academic non
      commercial research purposes at https://github.com/mattmattmattmatt/VASP.

PMID- 25755273
TI  - BMRF-Net: a software tool for identification of protein interaction subnetworks
      by a bagging Markov random field-based method.
AB  - Identification of protein interaction subnetworks is an important step to help us
      understand complex molecular mechanisms in cancer. In this paper, we develop a
      BMRF-Net package, implemented in Java and C++, to identify protein interaction
      subnetworks based on a bagging Markov random field (BMRF) framework. By
      integrating gene expression data and protein-protein interaction data, this
      software tool can be used to identify biologically meaningful subnetworks. A user
      friendly graphic user interface is developed as a Cytoscape plugin for the BMRF
      Net software to deal with the input/output interface. The detailed structure of
      the identified networks can be visualized in Cytoscape conveniently. The BMRF-Net
      package has been applied to breast cancer data to identify significant
      subnetworks related to breast cancer recurrence. AVAILABILITY AND IMPLEMENTATION:
      The BMRF-Net package is available at http://sourceforge.net/projects/bmrfcjava/.
      The package is tested under Ubuntu 12.04 (64-bit), Java 7, glibc 2.15 and
      Cytoscape 3.1.0.

PMID- 25755274
TI  - Engineering Giardia lamblia trimethylguanosine synthase (GlaTgs2) to transfer non
      natural modifications to the RNA 5'-cap.
AB  - Trimethylguanosine synthase from Giardia lamblia (GlaTgs2) naturally catalyzes
      methyl transfer from S-adenosyl-L-methionine (AdoMet) to the exocyclic N(2) atom
      of the 5'-cap--a hallmark of eukaryotic mRNAs. The wild-type enzyme shows
      substrate promiscuity and can also use the AdoMet-analog AdoPropen for allyl
      transfer. Here we report on engineering GlaTgs2 to enhance the activity on
      AdoPropen. A mutational analysis, involving an alanine scan of 10 residues
      located around the active site, was performed. Positions V34 and S38 were
      identified as mutational hot spots and analyzed in greater detail by testing NNK
      libraries. Kinetic analysis and thermostability measurements revealed V34A as the
      best variant of GlaTgs2, with a ~10-fold improved specificity for AdoPropen.
      Double mutants did not yield additional improvements due to low catalytic
      efficiencies and thermal destabilization. Homologous Tgs enzymes from Homo
      sapiens and G. intestinalis were also investigated regarding their catalytic
      activity on AdoPropen. While neither the human wild-type (WT) enzyme nor any of
      its variants showed activity on AdoPropen, the homologue from G. intestinalis
      (GinTgs) was remarkably active on AdoPropen. Introducing the best substitution at
      the homologous position led to variant T34A with ~40-fold higher specificity for
      AdoPropen than the original GlaTgs2 WT.

PMID- 25755275
TI  - Intentionality in Healing--The Voices of Men in Nursing: A Grounded Theory
      Investigation.
AB  - PURPOSE: The purpose of this study was to evaluate and potentially modify or
      expand a previously developed theory: Intentionality: The Matrix of Healing (IMH)
      using a sample of men in nursing. DESIGN: A modified grounded theory approach
      described by Chen and Boore (2009) and by Amsteus (2014). METHOD: Twelve men in
      nursing were recruited. Each was interviewed at least once and their feedback
      solicited to determine accuracy of interpretation. Results were compared and
      contrasted to those obtained from the earlier research with six female nurses and
      their patients. RESULTS: Both groups viewed intentionality as different from, and
      greater than, intention. Intentionality reflects the whole person's values,
      goals, and experiences. The men emphasized the importance of reflective spiritual
      practices, developing self-awareness, being aware of the stress experienced by
      males in a female profession, and the role of action in manifesting
      intentionality in healing. CONCLUSIONS: The theory is substantiated with minor
      changes in emphases. Further study is warranted to expand the understanding of
      this basic concept in nursing and healing.

PMID- 25755276
TI  - Cricket fast bowling workload patterns as risk factors for tendon, muscle, bone
      and joint injuries.
AB  - OBJECTIVE: To assess workload-related risk factors for injuries to particular
      tissue types in cricket fast bowlers. DESIGN: 235 fast bowlers who bowled in
      14600 player innings over a period of 15 years were followed in a prospective
      cohort risk factor study to compare overs bowled in each match (including
      preceding workload patterns) and injury risk in the 3-4 weeks subsequent to the
      match. Injuries were categorised according to the affected tissue type as either:
      bone stress, tendon injuries, muscle strain or joint injuries. Workload risk
      factors were examined using binomial logistic regression multivariate analysis,
      with a forward stepwise procedure requiring a significance of <0.05. RESULTS:
      High acute match workload and high previous season workload were risk factors for
      tendon injuries, but high medium term (3-month workload) was protective. For bone
      stress injuries, high medium term workload and low career workload were risk
      factors. For joint injuries, high previous season and career workload were risk
      factors. There was little relationship between muscle injury and workload
      although high previous season workload was slightly protective. CONCLUSIONS: The
      level of injury risk for some tissue types varies in response to preceding fast
      bowling workload, with tendon injuries most affected by workload patterns.
      Workload planning may need to be individualised, depending on individual
      susceptibility to various injury types. This study supports the theory that
      tendons are at lowest risk with consistent workloads and susceptible to injury
      with sudden upgrades in workload. Gradual upgrades are recommended, particularly
      at the start of a bowler's career to reduce the risk of bone stress injury.

PMID- 25755277
TI  - Epidemiological and clinical outcome comparison of indirect ('strain') versus
      direct ('contusion') anterior and posterior thigh muscle injuries in male elite
      football players: UEFA Elite League study of 2287 thigh injuries (2001-2013).
AB  - BACKGROUND: Data regarding direct athletic muscle injuries (caused by a direct
      blunt or sharp external force) compared to indirect ones (without the influence
      of a direct external trauma) are missing in the current literature--this
      distinction has clinical implications. AIM: To compare incidence, duration of
      absence and characteristics of indirect and direct anterior (quadriceps) and
      posterior thigh (hamstring) muscle injuries. METHODS: 30 football teams and 1981
      players were followed prospectively from 2001 until 2013. The team medical staff
      recorded individual player exposure and time-loss injuries. Muscle injuries were
      defined as indirect or direct according to their injury mechanism. RESULTS: In
      total, 2287 thigh muscle injuries were found, representing 25% of all injuries.
      Two thousand and three were valid for further analysis, of which 88% were
      indirect and 12% direct. The incidence was eight times higher for indirect
      injuries (1.48/1000 h) compared to direct muscle injuries (0.19/1000 h) (p<0.01).
      Indirect muscle injuries caused 19% of total absence, and direct injuries 1%. The
      mean lay-off time for indirect injuries amounted to 18.5 days and differed
      significantly from direct injuries which accounted for 7 days (p<0.001). 60% of
      indirect injuries and 76% of direct injuries occurred in match situations. Foul
      play was involved in 7% of all thigh muscle injuries, as well as in 2% of
      indirect injuries and 42% of direct injuries. SUMMARY: Muscle anterior and
      posterior thigh injuries in elite football are more frequent than have been
      previously described. Direct injuries causing time loss are less frequent than
      indirect ones, and players can usually return to full activity in under half the
      average time for an indirect injury. Foul play is involved in 7.5% of all thigh
      muscle injuries.

PMID- 25755278
TI  - Protein kinase C-dependent growth-associated protein 43 phosphorylation regulates
      gephyrin aggregation at developing GABAergic synapses.
AB  - Growth-associated protein 43 (GAP43) is known to regulate axon growth, but
      whether it also plays a role in synaptogenesis remains unclear. Here, we found
      that GAP43 regulates the aggregation of gephyrin, a pivotal protein for
      clustering postsynaptic GABA(A) receptors (GABA(A)Rs), in developing cortical
      neurons. Pharmacological blockade of either protein kinase C (PKC) or neuronal
      activity increased both GAP43-gephyrin association and gephyrin misfolding
      induced aggregation, suggesting the importance of PKC-dependent regulation of
      GABAergic synapses. Furthermore, we found that PKC phosphorylation-resistant
      GAP43(S41A), but not PKC phosphorylation-mimicking GAP43(S41D), interacted with
      cytosolic gephyrin to trigger gephyrin misfolding and its sequestration into
      aggresomes. In contrast, GAP43(S41D), but not GAP43(S41A), inhibited the
      physiological aggregation/clustering of gephyrin, reduced surface GABA(A)Rs under
      physiological conditions, and attenuated gephyrin misfolding under transient
      oxygen-glucose deprivation (tOGD) that mimics pathological neonatal hypoxia.
      Calcineurin-mediated GAP43 dephosphorylation that accompanied tOGD also led to
      GAP43-gephyrin association and gephyrin misfolding. Thus, PKC-dependent
      phosphorylation of GAP43 plays a critical role in regulating postsynaptic
      gephyrin aggregation in developing GABAergic synapses.

PMID- 25755279
TI  - Nuclear Export of Smads by RanBP3L Regulates Bone Morphogenetic Protein Signaling
      and Mesenchymal Stem Cell Differentiation.
AB  - Bone morphogenetic proteins (BMPs) play vital roles in regulating stem cell
      maintenance and differentiation. BMPs can induce osteogenesis and inhibit
      myogenesis of mesenchymal stem cells. Canonical BMP signaling is stringently
      controlled through reversible phosphorylation and nucleocytoplasmic shuttling of
      Smad1, Smad5, and Smad8 (Smad1/5/8). However, how the nuclear export of Smad1/5/8
      is regulated remains unclear. Here we report that the Ran-binding protein RanBP3L
      acts as a nuclear export factor for Smad1/5/8. RanBP3L directly recognizes
      dephosphorylated Smad1/5/8 and mediates their nuclear export in a Ran-dependent
      manner. Increased expression of RanBP3L blocks BMP-induced osteogenesis of mouse
      bone marrow-derived mesenchymal stem cells and promotes myogenic induction of
      C2C12 mouse myoblasts, whereas depletion of RanBP3L expression enhances BMP
      dependent stem cell differentiation activity and transcriptional responses. In
      conclusion, our results demonstrate that RanBP3L, as a nuclear exporter for BMP
      specific Smads, plays a critical role in terminating BMP signaling and regulating
      mesenchymal stem cell differentiation. 

PMID- 25755280
TI  - PATZ1 Is a DNA Damage-Responsive Transcription Factor That Inhibits p53 Function.
AB  - Insults to cellular health cause p53 protein accumulation, and loss of p53
      function leads to tumorigenesis. Thus, p53 has to be tightly controlled. Here we
      report that the BTB/POZ domain transcription factor PATZ1 (MAZR), previously
      known for its transcriptional suppressor functions in T lymphocytes, is a crucial
      regulator of p53. The novel role of PATZ1 as an inhibitor of the p53 protein
      marks its gene as a proto-oncogene. PATZ1-deficient cells have reduced
      proliferative capacity, which we assessed by transcriptome sequencing (RNA-Seq)
      and real-time cell growth rate analysis. PATZ1 modifies the expression of p53
      target genes associated with cell proliferation gene ontology terms. Moreover,
      PATZ1 regulates several genes involved in cellular adhesion and morphogenesis.
      Significantly, treatment with the DNA damage-inducing drug doxorubicin results in
      the loss of the PATZ1 transcription factor as p53 accumulates. We find that PATZ1
      binds to p53 and inhibits p53-dependent transcription activation. We examine the
      mechanism of this functional inhibitory interaction and demonstrate that PATZ1
      excludes p53 from DNA binding. This study documents PATZ1 as a novel player in
      the p53 pathway. 

PMID- 25755281
TI  - WNT/beta-Catenin Signaling Regulates Multiple Steps of Myogenesis by Regulating
      Step-Specific Targets.
AB  - Molecules involved in WNT/beta-catenin signaling show specific spatiotemporal
      expression and play vital roles in myogenesis; however, it is still largely
      unknown how WNT/beta-catenin signaling regulates each step of myogenesis. Here,
      we show that WNT/beta-catenin signaling can control diverse biological processes
      of myogenesis by regulating step-specific molecules. In order to identify the
      temporally specific roles of WNT/beta-catenin signaling molecules in muscle
      development and homeostasis, we used in vitro culture systems for both primary
      mouse myoblasts and C2C12 cells, which can differentiate into myofibers. We found
      that a blockade of WNT/beta-catenin signaling in the proliferating cells
      decreases proliferation activity, but does not induce cell death, through the
      regulation of genes cyclin A2 (Ccna2) and cell division cycle 25C (Cdc25c).
      During muscle differentiation, the inhibition of WNT/beta-catenin signaling
      blocks myoblast fusion through the inhibition of the Fermitin family homolog 2
      (Fermt2) gene. Blocking WNT/beta-catenin signaling in the well-differentiated
      myofibers results in the failure of maintenance of their structure by disruption
      of cadherin/beta-catenin/actin complex formation, which plays a crucial role in
      connecting a myofiber's cytoskeleton to the surrounding extracellular matrix.
      Thus, our results indicate that WNT/beta-catenin signaling can regulate multiple
      steps of myogenesis, including cell proliferation, myoblast fusion, and
      homeostasis, by targeting step-specific molecules. 

PMID- 25755282
TI  - Vaccinia-Related Kinase 2 Controls the Stability of the Eukaryotic Chaperonin
      TRiC/CCT by Inhibiting the Deubiquitinating Enzyme USP25.
AB  - Molecular chaperones monitor the proper folding of misfolded proteins and
      function as the first line of defense against mutant protein aggregation in
      neurodegenerative diseases. The eukaryotic chaperonin TRiC is a potent suppressor
      of mutant protein aggregation and toxicity in early stages of disease
      progression. Elucidation of TRiC functional regulation will enable us to better
      understand the pathological mechanisms of neurodegeneration. We have previously
      shown that vaccinia-related kinase 2 (VRK2) downregulates TRiC protein levels
      through the ubiquitin-proteasome system by recruiting the E3 ligase COP1.
      However, although VRK2 activity was necessary in TRiC downregulation, the
      phosphorylated substrate was not determined. Here, we report that USP25 is a
      novel TRiC interacting protein that is also phosphorylated by VRK2. USP25
      catalyzed deubiquitination of the TRiC protein and stabilized the chaperonin,
      thereby reducing accumulation of misfolded polyglutamine protein aggregates.
      Notably, USP25 deubiquitinating activity was suppressed when VRK2 phosphorylated
      the Thr(680), Thr(727), and Ser(745) residues. Impaired USP25 deubiquitinating
      activity after VRK2-mediated phosphorylation may be a critical pathway in TRiC
      protein destabilization. 

PMID- 25755283
TI  - Poly(Q) Expansions in ATXN7 Affect Solubility but Not Activity of the SAGA
      Deubiquitinating Module.
AB  - Spinocerebellar ataxia type 7 (SCA7) is a debilitating neurodegenerative disease
      caused by expansion of a polyglutamine [poly(Q)] tract in ATXN7, a subunit of the
      deubiquitinase (DUB) module (DUBm) in the SAGA complex. The effects of ATXN7
      poly(Q) on DUB activity are not known. To address this important question, we
      reconstituted the DUBm in vitro with either wild-type ATXN7 or a pathogenic form,
      ATXN7-92Q NT, with 92 Q residues at the N terminus (NT). We found that both forms
      of ATXN7 greatly enhance DUB activity but that ATXN7-92Q NT is largely insoluble
      unless it is incorporated into the DUBm. Cooverexpression of DUBm components in
      human astrocytes also promoted the solubility of ATXN7-92Q, inhibiting its
      aggregation into nuclear inclusions that sequester DUBm components, leading to
      global increases in ubiquitinated H2B (H2Bub) levels. Global H2Bub levels were
      also increased in the cerebellums of mice in a SCA7 mouse model. Our findings
      indicate that although ATXN7 poly(Q) expansions do not change the enzymatic
      activity of the DUBm, they likely contribute to SCA7 by initiating aggregates
      that sequester the DUBm away from its substrates. 

PMID- 25755284
TI  - The C2 Domain and Altered ATP-Binding Loop Phosphorylation at Ser359 Mediate the
      Redox-Dependent Increase in Protein Kinase C-delta Activity.
AB  - The diverse roles of protein kinase C-delta (PKCdelta) in cellular growth,
      survival, and injury have been attributed to stimulus-specific differences in
      PKCdelta signaling responses. PKCdelta exerts membrane-delimited actions in cells
      activated by agonists that stimulate phosphoinositide hydrolysis. PKCdelta is
      released from membranes as a Tyr(313)-phosphorylated enzyme that displays a high
      level of lipid-independent activity and altered substrate specificity during
      oxidative stress. This study identifies an interaction between PKCdelta's
      Tyr(313)-phosphorylated hinge region and its phosphotyrosine-binding C2 domain
      that controls PKCdelta's enzymology indirectly by decreasing phosphorylation in
      the kinase domain ATP-positioning loop at Ser(359). We show that wild-type (WT)
      PKCdelta displays a strong preference for substrates with serine as the
      phosphoacceptor residue at the active site when it harbors phosphomimetic or
      bulky substitutions at Ser(359.) In contrast, PKCdelta-S359A displays lipid
      independent activity toward substrates with either a serine or threonine as the
      phosphoacceptor residue. Additional studies in cardiomyocytes show that oxidative
      stress decreases Ser(359) phosphorylation on native PKCdelta and that PKCdelta
      S359A overexpression increases basal levels of phosphorylation on substrates with
      both phosphoacceptor site serine and threonine residues. Collectively, these
      studies identify a C2 domain-pTyr(313) docking interaction that controls ATP
      positioning loop phosphorylation as a novel, dynamically regulated, and
      physiologically relevant structural determinant of PKCdelta catalytic activity. 

PMID- 25755285
TI  - The Human GATA1 Gene Retains a 5' Insulator That Maintains Chromosomal
      Architecture and GATA1 Expression Levels in Splenic Erythroblasts.
AB  - GATA1 is a key transcription factor for erythropoiesis. GATA1 gene expression is
      strictly regulated at the transcriptional level. While the regulatory mechanisms
      governing mouse Gata1 (mGata1) gene expression have been studied extensively, how
      expression of the human GATA1 (hGATA1) gene is regulated remains to be
      elucidated. To address this issue, we generated hGATA1 bacterial artificial
      chromosome (BAC) transgenic mouse lines harboring a 183-kb hGATA1 locus covering
      the hGATA1 exons and distal flanking sequences. Transgenic hGATA1 expression
      coincides with endogenous mGata1 expression and fully rescues hematopoietic
      deficiency in mGata1 knockdown mice. The transgene exhibited copy number
      dependent and integration position-independent expression of hGATA1, indicating
      the presence of chromatin insulator activity within the transgene. We found a
      novel insulator element at 29 kb 5' to the hGATA1 gene and refer to this element
      as the 5' CCCTC-binding factor (CTCF) site. Substitution mutation of the 5' CTCF
      site in the hGATA1 BAC disrupted the chromatin architecture and led to a
      reduction of hGATA1 expression in splenic erythroblasts under conditions of
      stress erythropoiesis. Our results demonstrate that expression of the hGATA1 gene
      is regulated through the chromatin architecture organized by 5' CTCF site
      mediated intrachromosomal interactions in the hGATA1 locus. 

PMID- 25755286
TI  - Elongation Factor 2 Kinase Is Regulated by Proline Hydroxylation and Protects
      Cells during Hypoxia.
AB  - Protein synthesis, especially translation elongation, requires large amounts of
      energy, which is often generated by oxidative metabolism. Elongation is
      controlled by phosphorylation of eukaryotic elongation factor 2 (eEF2), which
      inhibits its activity and is catalyzed by eEF2 kinase (eEF2K), a
      calcium/calmodulin-dependent alpha-kinase. Hypoxia causes the activation of eEF2K
      and induces eEF2 phosphorylation independently of previously known inputs into
      eEF2K. Here, we show that eEF2K is subject to hydroxylation on proline-98.
      Proline hydroxylation is catalyzed by proline hydroxylases, oxygen-dependent
      enzymes which are inactivated during hypoxia. Pharmacological inhibition of
      proline hydroxylases also stimulates eEF2 phosphorylation. Pro98 lies in a
      universally conserved linker between the calmodulin-binding and catalytic domains
      of eEF2K. Its hydroxylation partially impairs the binding of calmodulin to eEF2K
      and markedly limits the calmodulin-stimulated activity of eEF2K. Neuronal cells
      depend on oxygen, and eEF2K helps to protect them from hypoxia. eEF2K is the
      first example of a protein directly involved in a major energy-consuming process
      to be regulated by proline hydroxylation. Since eEF2K is cytoprotective during
      hypoxia and other conditions of nutrient insufficiency, it may be a valuable
      target for therapy of poorly vascularized solid tumors. 

PMID- 25755287
TI  - Maternal nutrition modifies trophoblast giant cell phenotype and fetal growth in
      mice.
AB  - Mammalian placentation is dependent upon the action of trophoblast cells at the
      time of implantation. Appropriate fetal growth, regulated by maternal nutrition
      and nutrient transport across the placenta, is a critical factor for adult
      offspring long-term health. We have demonstrated that a mouse maternal low
      protein diet (LPD) fed exclusively during preimplantation development (Emb-LPD)
      increases offspring growth but programmes adult cardiovascular and metabolic
      disease. In this study, we investigate the impact of maternal nutrition on post
      implantation trophoblast phenotype and fetal growth. Ectoplacental cone explants
      were isolated at day 8 of gestation from female mice fed either normal protein
      diet (NPD: 18% casein), LPD (9% casein) or Emb-LPD and cultured in vitro. We
      observed enhanced spreading and cell division within proliferative and secondary
      trophoblast giant cells (TGCs) emerging from explants isolated from LPD-fed
      females when compared with NPD and Emb-LPD explants after 24 and 48 h. Moreover,
      both LPD and Emb-LPD explants showed substantial expansion of TGC area during 24
      48 h, not observed in NPD. No difference in invasive capacity was observed
      between treatments using Matrigel transwell migration assays. At day 17 of
      gestation, LPD- and Emb-LPD-fed conceptuses displayed smaller placentas and
      larger fetuses respectively, resulting in increased fetal:placental ratios in
      both groups compared with NPD conceptuses. Analysis of placental and yolk sac
      nutrient signalling within the mammalian target of rapamycin complex 1 pathway
      revealed similar levels of total and phosphorylated downstream targets across
      groups. These data demonstrate that early post-implantation embryos modify
      trophoblast phenotype to regulate fetal growth under conditions of poor maternal
      nutrition.

PMID- 25755288
TI  - Heart rate variability density analysis (Dyx) for identification of appropriate
      implantable cardioverter defibrillator recipients among elderly patients with
      acute myocardial infarction and left ventricular systolic dysfunction.
AB  - AIMS: Dyx is a new heart rate variability (HRV) density analysis specifically
      designed to identify patients at high risk for malignant ventricular arrhythmias.
      The aim of this study was to test if Dyx can improve risk stratification for
      malignant ventricular tachyarrhythmias and to test if the previously identified
      cut-off can be reproduced. METHODS AND RESULTS: This study included 248 patients
      from the CARISMA study with ejection fraction <=40% after an acute myocardial
      infarction and an analysable 24 h Holter recording. All patients received an
      implantable cardiac monitor, which was used to diagnose the primary endpoint of
      near-fatal or fatal ventricular tachyarrhythmias likely preventable by an
      implantable cardioverter defibrillator (ICD), during a period of 2 years. A Dyx
      <= 1.96 was considered abnormal. The secondary endpoint was cardiovascular death.
      At enrolment 59 patients (24%) had a Dyx <= 1.96 and 20 experienced a primary
      endpoint. A Dyx <= 1.96 was associated with a significantly increased risk for
      malignant arrhythmias [hazards ratio (HR) = 4.36 (1.81-10.52), P = 0.001] and
      cardiovascular death [HR = 3.47 (1.38-8.74), P = 0.008]. Compared with important
      clinical risk parameters (age >70 years and QRS > 120 ms), Dyx <= 1.96
      significantly added predictive value (P = 0.0066). CONCLUSIONS: Dyx was a better
      predictor of ventricular tachyarrhythmias than the traditional measures of HRV
      and heart rate turbulence, particularly in the elderly. Dyx might be a useful
      tool for better selection of ICD candidates in the elderly population, since a
      normal Dyx in this group was associated with a very low risk for malignant
      ventricular arrhythmias.ClinicalTrials.gov Identifier NCT00145119.

PMID- 25755289
TI  - Reduced pre-hospital and in-hospital survival rates after out-of-hospital cardiac
      arrest of patients with type-2 diabetes mellitus: an observational prospective
      community-based study.
AB  - AIMS: Out-of-hospital cardiac arrest (OHCA) remains a major cause of death. We
      aimed to determine whether type-2 diabetes mellitus (T2DM) is associated with
      reduced pre-hospital and in-hospital survival rates after OHCA. METHODS AND
      RESULTS: An observational community-based cohort study was performed among 1549
      OHCA patients with ECG-documented ventricular tachycardia/ventricular
      fibrillation (VT/VF). We compared pre-hospital and in-hospital survival rates
      between T2DM patients and non-diabetic patients. Analyses among T2DM patients
      were stratified according to current T2DM treatment, used as proxy for T2DM
      severity. Proportions of neurologically intact survival were analysed. Pre
      hospital survival rates were lower in T2DM patients (n = 275) than in non
      diabetic patients (n = 1274); 48.7 vs. 55.8% (univariate P = 0.032). Type-2
      diabetes mellitus was associated with lower pre-hospital survival [OR 0.75 (0.58
      0.98); after evaluation of the risk factors, we found no relevant confounding].
      Patients treated with insulin only had lower pre-hospital survival rates than
      patients treated with oral glucose-lowering drugs only (37.3 vs. 53.3%,
      univariate P = 0.034), partially explained by location of OHCA and EMS response
      time [ORadj 0.62 (0.33-1.17)]. In-hospital survival rates were also lower in T2DM
      patients (n = 134) than in non-diabetic patients (n = 711); 40.3 vs. 57.7%,
      univariate P < 0.001. In those patients whose cause of OHCA was retrieved (n =
      771), T2DM was significantly associated with lower in-hospital survival [ORadj
      0.57 (0.37-0.87)]. Neurologically intact status at discharge was similarly high
      among T2DM and non-diabetic patients (94.4 vs. 94.6%, P = 0.954). CONCLUSION:
      T2DM is associated with lower pre-hospital and in-hospital survival rates after
      OHCA. Neurologically intact status at hospital discharge is high both among T2DM
      and non-diabetic patients.

PMID- 25755290
TI  - The story of ... a lead.
AB  - The totally transvenous implantable defibrillator lead, conceived by Mirowski and
      Mower 45 years ago, is irrevocably related to the wide acceptance of this
      therapy. It paved the way for the era for non-thoracotomy implantation. This
      paper covers the most important details of the evolution--over this 45-year
      period--of the original (ENDOTAK) transvenous ICD lead and subsequent iterations.
      Over that time period, there have been over 800 000 patients implanted with this
      family of leads. The 'story' addresses the multiple problems encountered,
      technological improvements in materials, design, and testing to overcome them.
      And, the need for continued close collaboration between physicians and industry
      focused on reliability and longevity of this critical component of these life
      saving systems.

PMID- 25755291
TI  - The Bruton tyrosine kinase inhibitor ibrutinib with chemoimmunotherapy in
      patients with chronic lymphocytic leukemia.
AB  - The safety and efficacy of ibrutinib, an oral inhibitor of Bruton tyrosine
      kinase, were evaluated with chemoimmunotherapy (CIT) in a multicenter phase 1b
      study. Patients with relapsed/refractory chronic lymphocytic leukemia received
      bendamustine and rituximab (BR) or fludarabine, cyclophosphamide, and rituximab
      (FCR) for up to 6 cycles with daily ibrutinib (420 mg) until progressive disease
      or unacceptable toxicity. Enrollment to FCR-ibrutinib closed early due to a lack
      of fludarabine-naive previously treated patients. No patients treated with BR
      ibrutinib (n = 30) or FCR-ibrutinib (n = 3) experienced prolonged hematologic
      toxicity in cycle 1 (primary end point). Tolerability was as expected with either
      CIT or single-agent ibrutinib. The overall response rate (ORR) with BR-ibrutinib
      was 93.3%, including 16.7% complete responses (CRs) initially, which increased to
      40% with the extension period. Including 1 patient with partial response with
      lymphocytosis, the best ORR was 96.7%. Sixteen of 21 patients with baseline
      cytopenias had sustained hematologic improvement. At 12 and 36 months, 86.3% and
      70.3% remained progression-free, respectively. All 3 patients treated with
      ibrutinib-FCR achieved CR. Ibrutinib may enhance CIT efficacy without additive
      toxicities, providing the rationale for studying this combination in an ongoing
      phase 3 trial. The study is registered to www.clinicaltrials.gov as #NCT01292135.

PMID- 25755292
TI  - Elucidation of the EP defect in Diamond-Blackfan anemia by characterization and
      prospective isolation of human EPs.
AB  - Diamond-Blackfan anemia (DBA) is a disorder characterized by a selective defect
      in erythropoiesis. Delineation of the precise defect is hampered by a lack of
      markers that define cells giving rise to erythroid burst- and erythroid colony
      forming unit (BFU-E and CFU-E) colonies, the clonogenic assays that quantify
      early and late erythroid progenitor (EEP and LEP) potential, respectively. By
      combining flow cytometry, cell-sorting, and single-cell clonogenic assays, we
      identified Lin(-)CD34(+)CD38(+)CD45RA(-)CD123(-)CD71(+)CD41a(-)CD105(-)CD36(-)
      bone marrow cells as EEP giving rise to BFU-E, and Lin(-)CD34(+/-)CD38(+)CD45RA(
      )CD123(-)CD71(+)CD41a(-)CD105(+)CD36(+) cells as LEP giving rise to CFU-E, in a
      hierarchical fashion. We then applied these definitions to DBA and identified
      that, compared with controls, frequency, and clonogenicity of DBA, EEP and LEP
      are significantly decreased in transfusion-dependent but restored in
      corticosteroid-responsive patients. Thus, both quantitative and qualitative
      defects in erythroid progenitor (EP) contribute to defective erythropoiesis in
      DBA. Prospective isolation of defined EPs will facilitate more incisive study of
      normal and aberrant erythropoiesis. 

PMID- 25755293
TI  - Women in medicine: historical perspectives and recent trends.
AB  - INTRODUCTION: Women now outnumber men in British medical schools. This paper
      charts the history of women in medicine and provides current demographic trends.
      SOURCES OF DATA: A historical literature review and routinely collected data from
      Department of Health and the Health and Social Care Information Centre. AREAS OF
      AGREEMENT: Clear gender differences are apparent in working practices, including
      greater likelihood of working part time and specializing in certain areas of
      medicine. AREAS OF CONTROVERSY: The increasing need to increase activity among
      the existing medical workforce is timely amidst a changing workforce demographic.
      GROWING POINTS: Workforce planners, policymakers and Royal Colleges should
      continue to develop interventions that may reduce disparities in career choices,
      as well as considering ways to increase participation and activity. AREAS TIMELY
      FOR DEVELOPING RESEARCH: Further research is needed to explore the cost
      effectiveness of existing and future interventions in this field.

PMID- 25755294
TI  - An Integrated Platform for Isolation, Processing, and Mass Spectrometry-based
      Proteomic Profiling of Rare Cells in Whole Blood.
AB  - Isolation and molecular characterization of rare cells (e.g. circulating tumor
      and stem cells) within biological fluids and tissues has significant potential in
      clinical diagnostics and personalized medicine. The present work describes an
      integrated platform of sample procurement, preparation, and analysis for deep
      proteomic profiling of rare cells in blood. Microfluidic magnetophoretic
      isolation of target cells spiked into 1 ml of blood at the level of 1000-2000
      cells/ml, followed by focused acoustics-assisted sample preparation has been
      coupled with one-dimensional PLOT-LC-MS methodology. The resulting zeptomole
      detection sensitivity enabled identification of ~4000 proteins with injection of
      the equivalent of only 100-200 cells per analysis. The characterization of rare
      cells in limited volumes of physiological fluids is shown by the isolation and
      quantitative proteomic profiling of first MCF-7 cells spiked into whole blood as
      a model system and then two CD133+ endothelial progenitor and hematopoietic cells
      in whole blood from volunteers. 

PMID- 25755295
TI  - Large-Scale Targeted Proteomics Using Internal Standard Triggered-Parallel
      Reaction Monitoring (IS-PRM).
AB  - Targeted high-resolution and accurate mass analyses performed on fast sequencing
      mass spectrometers have opened new avenues for quantitative proteomics. More
      specifically, parallel reaction monitoring (PRM) implemented on quadrupole
      orbitrap instruments exhibits exquisite selectivity to discriminate interferences
      from analytes. Furthermore, the instrument trapping capability enhances the
      sensitivity of the measurements. The PRM technique, applied to the analysis of
      limited peptide sets (typically 50 peptides or less) in a complex matrix,
      resulted in an improved detection and quantification performance as compared with
      the reference method of selected reaction monitoring performed on triple
      quadrupole instruments. However, the implementation of PRM for the analysis of
      large peptide numbers requires the adjustment of mass spectrometry acquisition
      parameters, which affects dramatically the quality of the generated data, and
      thus the overall output of an experiment. A newly designed data acquisition
      scheme enabled the analysis of moderate-to-large peptide numbers while retaining
      a high performance level. This new method, called internal standard triggered
      parallel reaction monitoring (IS-PRM), relies on added internal standards and the
      on-the-fly adjustment of acquisition parameters to drive in real-time measurement
      of endogenous peptides. The acquisition time management was designed to maximize
      the effective time devoted to measure the analytes in a time-scheduled targeted
      experiment. The data acquisition scheme alternates between two PRM modes: a fast
      low-resolution "watch mode" and a "quantitative mode" using optimized parameters
      ensuring data quality. The IS-PRM method exhibited a highly effective use of the
      instrument time. Applied to the analysis of large peptide sets (up to 600) in
      complex samples, the method showed an unprecedented combination of scale and
      analytical performance, with limits of quantification in the low amol range. The
      successful analysis of various types of biological samples augurs a broad
      applicability of the method, which is likely to benefit a wide range of
      proteomics experiments. 

PMID- 25755296
TI  - Simultaneous Quantification of Viral Antigen Expression Kinetics Using Data
      Independent (DIA) Mass Spectrometry.
AB  - The generation of antigen-specific reagents is a significant bottleneck in the
      study of complex pathogens that express many hundreds to thousands of different
      proteins or to emerging or new strains of viruses that display potential pandemic
      qualities and therefore require rapid investigation. In these instances the
      development of antibodies for example can be prohibitively expensive to cover the
      full pathogen proteome, or the lead time may be unacceptably long in urgent cases
      where new highly pathogenic viral strains may emerge. Because genomic information
      on such pathogens can be rapidly acquired this opens up avenues using mass
      spectrometric approaches to study pathogen antigen expression, host responses and
      for screening the utility of therapeutics. In particular, data-independent
      acquisition (DIA) modalities on high-resolution mass spectrometers generate
      spectral information on all components of a complex sample providing depth of
      coverage hitherto only seen in genomic deep sequencing. The spectral information
      generated by DIA can be iteratively interrogated for potentially any protein of
      interest providing both evidence of protein expression and quantitation. Here we
      apply a solely DIA mass spectrometry based methodology to profile the viral
      antigen expression in cells infected with vaccinia virus up to 9 h post infection
      without the need for antigen specific antibodies or other reagents. We
      demonstrate deep coverage of the vaccinia virus proteome using a SWATH-MS
      acquisition approach, extracting quantitative kinetics of 100 virus proteins
      within a single experiment. The results highlight the complexity of vaccinia
      protein expression, complementing what is known at the transcriptomic level, and
      provide a valuable resource and technique for future studies of viral infection
      and replication kinetics. Furthermore, they highlight the utility of DIA and mass
      spectrometry in the dissection of host-pathogen interactions. 

PMID- 25755297
TI  - System-wide Analysis of SUMOylation Dynamics in Response to Replication Stress
      Reveals Novel Small Ubiquitin-like Modified Target Proteins and Acceptor Lysines
      Relevant for Genome Stability.
AB  - Genotoxic agents can cause replication fork stalling in dividing cells because of
      DNA lesions, eventually leading to replication fork collapse when the damage is
      not repaired. Small Ubiquitin-like Modifiers (SUMOs) are known to counteract
      replication stress, nevertheless, only a small number of relevant SUMO target
      proteins are known. To address this, we have purified and identified SUMO-2
      target proteins regulated by replication stress in human cells. The developed
      methodology enabled single step purification of His10-SUMO-2 conjugates under
      denaturing conditions with high yield and high purity. Following statistical
      analysis on five biological replicates, a total of 566 SUMO-2 targets were
      identified. After 2 h of hydroxyurea treatment, 10 proteins were up-regulated for
      SUMOylation and two proteins were down-regulated for SUMOylation, whereas after
      24 h, 35 proteins were up-regulated for SUMOylation, and 13 proteins were down
      regulated for SUMOylation. A site-specific approach was used to map over 1000
      SUMO-2 acceptor lysines in target proteins. The methodology is generic and is
      widely applicable in the ubiquitin field. A large subset of these identified
      proteins function in one network that consists of interacting replication
      factors, transcriptional regulators, DNA damage response factors including MDC1,
      ATR-interacting protein ATRIP, the Bloom syndrome protein and the BLM-binding
      partner RMI1, the crossover junction endonuclease EME1, BRCA1, and CHAF1A.
      Furthermore, centromeric proteins and signal transducers were dynamically
      regulated by SUMOylation upon replication stress. Our results uncover a
      comprehensive network of SUMO target proteins dealing with replication damage and
      provide a framework for detailed understanding of the role of SUMOylation to
      counteract replication stress. Ultimately, our study reveals how a post
      translational modification is able to orchestrate a large variety of different
      proteins to integrate different nuclear processes with the aim of dealing with
      the induced DNA damage. 

PMID- 25755298
TI  - Quantitative proteome analysis of temporally resolved phagosomes following uptake
      via key phagocytic receptors.
AB  - Macrophages operate at the forefront of innate immunity and their discrimination
      of foreign versus "self" particles is critical for a number of responses
      including efficient pathogen killing, antigen presentation, and cytokine
      induction. In order to efficiently destroy the particles and detect potential
      threats, macrophages express an array of receptors to sense and phagocytose prey
      particles. In this study, we accurately quantified a proteomic time-course of
      isolated phagosomes from murine bone marrow-derived macrophages induced by
      particles conjugated to seven different ligands representing pathogen-associated
      molecular patterns, immune opsonins or apoptotic cell markers. We identified a
      clear functional differentiation over the three timepoints and detected subtle
      differences between certain ligand-phagosomes, indicating that triggering of
      receptors through a single ligand type has mild, but distinct, effects on
      phagosome proteome and function. Moreover, our data shows that uptake of
      phosphatidylserine-coated beads induces an active repression of NF-kappaB immune
      responses upon Toll-like receptor (TLR)-activation by recruitment of anti
      inflammatory regulators to the phagosome. This data shows for the first time a
      systematic time-course analysis of bone marrow-derived macrophages phagosomes and
      how phagosome fate is regulated by the receptors triggered for phagocytosis. 

PMID- 25755299
TI  - Histone Deacetylase Inhibitors (HDACi) Cause the Selective Depletion of
      Bromodomain Containing Proteins (BCPs).
AB  - Histone deacetylases (HDACs) and acetyltransferases control the epigenetic
      regulation of gene expression through modification of histone marks. Histone
      deacetylase inhibitors (HDACi) are small molecules that interfere with histone
      tail modification, thus altering chromatin structure and epigenetically
      controlled pathways. They promote apoptosis in proliferating cells and are
      promising anticancer drugs. While some HDACi have already been approved for
      therapy and others are in different phases of clinical trials, the exact
      mechanism of action of this drug class remains elusive. Previous studies have
      shown that HDACis cause massive changes in chromatin structure but only moderate
      changes in gene expression. To what extent these changes manifest at the protein
      level has never been investigated on a proteome-wide scale. Here, we have studied
      HDACi-treated cells by large-scale mass spectrometry based proteomics. We show
      that HDACi treatment affects primarily the nuclear proteome and induces a
      selective decrease of bromodomain-containing proteins (BCPs), the main readers of
      acetylated histone marks. By combining time-resolved proteome and transcriptome
      profiling, we show that BCPs are affected at the protein level as early as 12 h
      after HDACi treatment and that their abundance is regulated by a combination of
      transcriptional and post-transcriptional mechanisms. Using gene silencing, we
      demonstrate that the decreased abundance of BCPs is sufficient to mediate
      important transcriptional changes induced by HDACi. Our data reveal a new aspect
      of the mechanism of action of HDACi that is mediated by an interplay between
      histone acetylation and the abundance of BCPs. Data are available via
      ProteomeXchange with identifier PXD001660 and NCBI Gene Expression Omnibus with
      identifier GSE64689. 

PMID- 25755300
TI  - Gene by Social-Environment Interaction for Youth Delinquency and Violence: Thirty
      Nine Aggression-related Genes.
AB  - Complex human traits are likely to be affected by many environmental and genetic
      factors, and the interactions among them. However, previous gene-environment
      interaction (G*E) studies have typically focused on one or only a few genetic
      variants at a time. To provide a broader view of G*E, this study examines the
      relationship between 403 genetic variants from 39 genes and youth delinquency and
      violence. We find evidence that low social control is associated with greater
      genetic risk for delinquency and violence and high/moderate social control with
      smaller genetic risk for delinquency and violence. Our findings are consistent
      with prior G*E studies based on a small number of genetic variants, and, more
      importantly, we show that these findings still hold when a large number of
      genetic variants are considered simultaneously. A key implication of these
      findings is that the expression of multiple genes related to delinquency depends
      on the social environment: gene expression is likely to be amplified in low
      social-control environments but, tends to be suppressed in high/moderate-social
      control environments. This study not only deepens our understanding of how the
      social environment shapes individual behavior, but also provides important
      conceptual and methodological insights for future G*E research on complex human
      traits.

PMID- 25755301
TI  - Micro-poromechanics model of fluid-saturated chemically active fibrous media.
AB  - We have developed a micromechanics based model for chemically active saturated
      fibrous media that incorporates fiber network microstructure, chemical potential
      driven fluid flow, and micro-poromechanics. The stress-strain relationship of the
      dry fibrous media is first obtained by considering the fiber behavior. The
      constitutive relationships applicable to saturated media are then derived in the
      poromechanics framework using Hill's volume averaging. The advantage of this
      approach is that the resultant continuum model accounts for the discrete nature
      of the individual fibers while retaining a form suitable for porous materials. As
      a result, the model is able to predict the influence of micro-scale phenomena,
      such as the fiber pre-strain caused by osmotic effects and evolution of fiber
      network structure with loading, on the overall behavior and in particular, on the
      poromechanics parameters. Additionally, the model can describe fluid-flow related
      rate-dependent behavior under confined and unconfined conditions and varying
      chemical environments. The significance of the approach is demonstrated by
      simulating unconfined drained monotonic uniaxial compression under different
      surrounding fluid bath molarity, and fluid-flow related creep and relaxation at
      different loading-levels and different surrounding fluid bath molarity. The model
      predictions conform to the experimental observations for saturated soft fibrous
      materials. The method can potentially be extended to other porous materials such
      as bone, clays, foams and concrete.

PMID- 25755303
TI  - From the Editor's Desk.

PMID- 25755302
TI  - Influences of acute alcohol consumption, sexual precedence, and relationship
      motivation on women's relationship and sex appraisals and unprotected sex
      intentions.
AB  - Guided by the cognitive mediation model of sexual decision making (Norris,
      Masters, & Zawacki, 2004. Cognitive mediation of women's sexual decision making:
      The influence of alcohol, contextual factors, and background variables. Annual
      Review of Sex Research, 15, 258-296), we examined female social drinkers' (N =
      162) in-the-moment risky sexual decision making by testing how individual
      differences (relationship motivation) and situational factors (alcohol
      consumption and sexual precedence conditions) influenced cognitive appraisals and
      sexual outcomes in a hypothetical sexual scenario. In a path model, acute
      intoxication, sexual precedence, and relationship motivation interactively
      predicted primary relationship appraisals and independently predicted primary sex
      appraisals. Primary appraisals predicted secondary appraisals related to
      relationship and unprotected sex, which predicted unprotected sex intentions.
      Sexual precedence directly increased unprotected sex intentions. Findings support
      the cognitive mediation model and suggest that sexual risk reduction
      interventions should address alcohol, relationship, sexual, and cognitive
      factors.

PMID- 25755304
TI  - The value of molecular biomarkers in biliary tract cancer in the era of targeted
      therapy.

PMID- 25755305
TI  - Prevalence and risk factors of asymptomatic hepatitis C virus infection in
      bangladesh.
AB  - OBJECTIVES: There are paucity of information about prevalence and risk factor of
      hepatitis C virus (HCV) in Bangladesh. METHODS: Blood was collected from 1018
      randomly selected subjects from a semi-urban area of Bangladesh. Anti-HCVs were
      checked in the blood twice using a third-generation commercial kit. The data of
      the questionnaires were analyzed to find possible risk factors. RESULTS: Nine of
      the 1018 subjects (88%) were tested positive for anti-HCV. The HCV-positive
      subjects were >28 years old. Major risk factors for HCV infection were treatment
      by unqualified and traditional practitioners, history of mass-vaccination against
      smallpox, hair cutting and shaving by barbers, and body piercing. However, known
      risk factors such as blood transfusion, surgery, invasive therapy, and
      intravenous drug use were not detected in any HCV-infected subjects. CONCLUSION:
      Control of HCV infection in Bangladesh may be difficult because the risk factors
      are related to normal tradition and culture of Bangladeshi people.

PMID- 25755306
TI  - Use of stem cells for liver diseases-current scenario.
AB  - End-stage liver disease and liver failure are major health problems worldwide
      leading to high mortality and morbidity and high healthcare costs. Currently,
      orthotropic liver transplantation is the only effective treatment available to
      the patients of end-stage liver disease. However, a serious shortage of liver
      donors, high cost, and risk of organ rejection are the major obstacles to liver
      transplantation. Because of the ability of stem cells for differentiation into
      any tissue type, they have huge potential in therapy of various end-stage or
      degenerative diseases and traumatic injuries. Stem cell therapy has the potential
      to provide a valuable adjunct and alternative to liver transplantation and has
      immense potential in the management of end stage liver disease and liver failure.
      Stem cell therapy can be mediated by either a direct contribution to the
      functional hepatocyte population with embryonic, induced pluripotent, or adult
      stem cells or by promotion of endogenous regenerative processes with bone marrow
      derived stem cells. Initial translational studies have been encouraging and have
      suggested improved liver function in advanced chronic liver disease and enhanced
      liver regeneration after portal vein embolization and partial hepatic resection.
      Stem cells infusion in cirrhotic patients has improved liver parameters and could
      form a viable bridge to transplantation. The present review summarizes basic of
      stem cell biology relevant to clinicians and an update on recent advances on the
      management of liver diseases using stem cells. 

PMID- 25755308
TI  - Latent Mycobacterium tuberculosis Infection in Liver Transplant Recipients
      Controversies in Current Diagnosis and Management.
AB  - Liver transplantation for end-stage liver disease is increasingly being
      undertaken in India.(1) Routine tuberculin skin testing (TST) for latent
      Mycobacterium tuberculosis infection (LTBI) and isoniazid prophylaxis in TST
      positive liver-transplant recipients (LTRs) is recommended(2,3) but seldom
      implemented worldwide.(4-7) The role of TST-testing and isoniazid prophylaxis in
      LTRs remains further undefined in high prevalence areas, including India. We
      describe the burden of LTBI in LTRs; the epidemiological aspects of M.
      tuberculosis infection in high prevalence areas; identifiable risk factors for M.
      tuberculosis infection; the limitations of current diagnostic techniques for LTBI
      in LTRs and the efficacy and toxicity of isoniazid prophylaxis in TST-positive
      LTRs and suggest directions for future investigations in this area. 

PMID- 25755307
TI  - Interleukin 28B Polymorphisms and Hepatitis C-Translating the Association into
      Clinical Decision Making.
AB  - Host genetic factors have long been suspected to play a role in predicting
      outcome and treatment response in hepatitis C virus (HCV) infection. This was
      confirmed recently by three landmark genome-wide association studies (GWAS)
      published in 2009, which identified single nucleotide polymorphisms near the
      interleukin (IL) 28B region that were more common in responders to treatment.
      There has subsequently been rapidly increasing data regarding the significance of
      the IL28B polymorphism not only in response to therapy but also in spontaneous
      clearance of acute HCV infection. This clinical association of Il28B genotype
      with HCV may lead to personalized HCV therapy, where the clinician may tailor the
      duration and type of therapy for an individual patient. This review summarizes
      the available data on the impact of IL28B polymorphisms on HCV infection and
      discusses the possible approach to translate this association into clinical
      decision making for the treatment of HCV infection. 

PMID- 25755309
TI  - Erlotinib-induced Hepatotoxicity-Clinical Presentation and Successful Management:
      A Case Report.
AB  - Drug-induced liver injury (DILI) is a common occurrence in clinical practice in
      the present era because of frequent use of drugs and increase in patients who
      have increased susceptibility to DILI (because of underlying non-alcoholic
      steatohepatitis [NASH], chronic hepatitis C, chronic hepatitis B and alcoholic
      liver disease). DILI is the most common reason for withdrawal of an approved drug
      from the market. The overall mortality rate among patients hospitalized for DILI
      is approximately 10%. Erlotinib, a tyrosine kinase inhibitor of epidermal growth
      factor receptor (EGFR) is indicated for treatment of patients with locally
      advanced or metastatic non-small cell lung cancer and pancreatic cancer. The most
      common adverse effects associated with erlotinib use are rash and diarrhea. Liver
      function test (LFT) abnormalities are commonly associated with erlotinib use.
      Grade 2 (ALT elevations > 2.5-5* upper limit of normal [ULN]) LFT abnormalities
      are observed in around 4% of patients while Grade 3 (ALT < 5-20* ULN) are not
      reported. We report a case of acute hepatitis due to administration of erlotinib
      in 81-year-old gentleman diagnosed as having non-small cell lung cancer with
      metastasis to mediastinal lymph nodes and started on erlotinib 150 mg/day. This
      type of deep jaundice is very rare, and timely diagnosis and withdrawal of the
      drug saved the life of the patient. It is recommended that liver functions be
      closely monitored in those with hepatic impairment, who are also on other
      cytochrome P450 3A4 inhibitors such as ketoconazole, clarithromycin,
      voriconazole, etc. In conclusion, we report a case of DILI secondary to erlotinib
      with significant hyperbilirubinemia (> 5* ULN; grade 4) in absence of concomitant
      P450 inhibitor intake and liver metastases. As erlotinib is now commonly
      incorporated into treatment of advanced lung and pancreatic cancer, it is
      important that clinicians are aware of this potential complication in practice
      especially in elderly patients. 

PMID- 25755310
TI  - Association between Celiac Disease and Chronic Hepatitis C Virus Infection.
AB  - Celiac disease affects the proximal small intestine and is caused by a local
      immune response to dietary gluten. Celiac disease usually presents with chronic
      diarrhea; however, presentations with elevated hepatic transaminase levels in
      blood or with iron-deficiency anemia have been described. Celiac disease has been
      reported to be associated with autoimmune liver diseases. Hepatitis C virus (HCV)
      can also initiate autoimmune disease process. Therefore, HCV infection and celiac
      disease may occur together. Here, we describe 4 cases of celiac disease
      associated with chronic hepatitis C. This small case series indicates that
      chronic HCV infection and celiac disease are not causally associated. 

PMID- 25755311
TI  - Bleeding after endoscopic biliary sphincterotomy.
AB  - Bleeding during endoscopic sphincterotomy is a common complication. Sometimes
      bleeding occurs as a late complication after endoscopic retrograde
      cholangiopancreatography (ERCP). We describe a case in which bleeding happened
      during ERCP but detection was done after the completion of the procedure. The
      detection of bleeding allowed further evaluation and detection of hemobilia in
      this case. The removal of blood clots from inside common bile duct by repeat ERCP
      however led to an uneventful recovery without any morbidity. 

PMID- 25755312
TI  - Non-cirrhotic Portal Fibrosis and Gamma-Gandy Bodies.

PMID- 25755313
TI  - Hepatology elsewhere.

PMID- 25755314
TI  - INASL 2011 Quiz.

PMID- 25755315
TI  - Spectrum of idiopathic noncirrhotic portal hypertension.

PMID- 25755316
TI  - Phyllanthin of Standardized Phyllanthus amarus Extract Attenuates Liver Oxidative
      Stress in Mice and Exerts Cytoprotective Activity on Human Hepatoma Cell Line.
AB  - BACKGROUND: Phyllanthus amarus, a traditional herbal liver-protecting medicine,
      is known to contain an active ingredient phyllanthin. Many research studies and
      clinical trials performed in the past using this plant have given contentious
      results which clearly accentuates the need for the standardization of the
      extracts. AIM: In this study, P. amarus extract was standardized for phyllanthin
      content by high performance thin layer chromatography (HPTLC) and high
      performance liquid chromatography (HPLC) analysis. The preventive role of a
      standardized extract of P. amarus against CC14-induced hepatotoxicity in vivo and
      in vitro using mice model and human hepatoma HepG2 cell line, respectively, was
      investigated. METHODS: Phyllanthin was used as a marker phytochemical for the
      standardization of P. amarus extract. The extracts were verified for phyllanthin
      content by HPTLC and HPLC. Female mice were orally administered with CCl4 either
      with or without standardized P. amarus extract in three different doses.
      Similarly, the cytoprotective role of the standardized extract in vitro was
      studied in HepG2 cell line. RESULTS: Oral administration of CCl4 resulted in
      increased oxidative stress, decreased antioxidative defense, and liver injury.
      Treatment with P. amarus along with CCl4 significantly mitigated the increase in
      activities of liver marker enzymes, lipid peroxidation, and bilirubin content. It
      also increased the antioxidant enzymatic and non-enzymatic defense parameter
      levels. The results of the in vitro study conducted in HepG2 cells indicated that
      the hepatotoxin lowered 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium
      bromide (Mil) metabolism and increased the release of transaminases which were
      corrected with co-incubation with P. amarus. CONCLUSION: The study established a
      significant liver-protecting role of standardized P. amarus extract due to the
      presence of active ingredient phyllanthin.

PMID- 25755317
TI  - Hepatitis C virus infection among patients with chronic immune thrombocytopenic
      purpura in northern India.
AB  - BACKGROUND: Hepatitis C virus (HCV) has been reported to be associated with the
      occurrence of autoimmune disorders, including immune thrombocytopenic purpura
      (ITP). This has suggested that HCV could be responsible for thrombocytopenia in
      these patients. This study was performed to estimate the frequency of HCV
      infection in patients of chronic ITP (cITP), and to find the frequency of
      thrombocytopenia in chronic HCV infection. MATERIALS: A total of 150 subjects
      were included in the study. Fifty consecutive adult patients with cITP (< 6
      months' duration) and 50 age-matched patients with chronic HCV were included for
      comparison of platelet counts in two groups. Fifty age-matched healthy subjects
      were also included in the control group. All patients' sera were tested for the
      presence or absence of HCV-RNA. Anti-HCV antibodies were tested in patients as
      well as in controls. Complete blood count and examination of peripheral blood
      smear were done followed by bone-marrow aspiration to confirm the diagnosis of
      ITP. RESULTS: Three patients (6%) were tested positive for anti-HCV antibodies
      while no subject was positive in control group (P=0.24). The prevalence of severe
      thrombocytopenia (platelet counts <50,000/mL) was significantly higher in ITP
      patients compared with that in chronic HCV patients (P=0.0001). Thrombocytopenia
      occurred more frequently in patient with moderate to severe than mild stage of
      fibrosis (P=0.001). CONCLUSION: In conclusion, thrombocytopenia in ITP patients
      was not associated with HCV infection. The prevalence of thrombocytopenia was
      more common and more severe in ITP patients when compared with that in patients
      with chronic HCV. Thrombocytopenia in chronic HCV patients was related to the
      stage of fibrosis and to the duration of HCV infection.

PMID- 25755318
TI  - Prevalence of Genotype D and Precore/Core Promoter Mutations in Hepatitis B Virus
      infected Population of North India.
AB  - Hepatitis B virus (HBV) isolates (21) from Punjab (North India) were studied for
      genotype distribution and precore/core promoter mutations. Assays of alanine
      aminotransaminase (ALT) and HBeAg were performed in all isolates. Genotypes were
      determined in all the samples by restriction fragment length polymorphism and the
      precore/core promoter mutations were studied by amplification and by direct
      sequencing of precore/core promoter region. Sixty-two percent of the isolates had
      higher ALT levels and 57% of the isolates were HBeAg negative. It was observed
      that 90% of the isolates were HBV D genotype (subgenotype D1 and D2) and 10% of
      the isolates were HBV A genotype (subgenotype A1). Amplification and sequencing
      of the precore/core promoter region showed 1762(A-T) and 1764(G-A) mutations in
      29% and 19% of the isolates, respectively. 1809(C/T) mutation was observed in 71%
      of the isolates under study. Novel precore and core promoter mutations like
      1690(A), 1695(A/T/G), 1700(A/C), 1703(c), 1850(A) and 1915(A/G) were observed in
      HBV-infected population of the state of Punjab (North India). Deletion and
      insertional mutations were also observed in some patients. (J CLIN EXP HEPATOL
      2011;1:73-76). 

PMID- 25755319
TI  - Pathogenesis, diagnosis, and treatment of hepatic encephalopathy.
AB  - Hepatic encephalopathy (HE) is a neuropsychiatric disorder seen in patients with
      advanced liver disease or porto-systemic shunts. Based on etiology and severity
      of HE, the World Congress of Gastroenterology has divided HE into categories and
      sub-categories. Many user-friendly computer-based neuropsychiatric tests are
      being validated for diagnosing covert HE. Currently, emphasis is being given to
      view HE deficits as a continuous spectrum rather than distinct stages. Ammonia is
      believed to play crucial role in pathogenesis of HE via astrocyte swelling and
      cerebral edema. However, evidence has been building up which supports the
      synergistic role of oxidative stress, inflammation and neurosteroids in
      pathogenesis of HE. At present, treatment of HE aims at decreasing the production
      and intestinal absorption of ammonia. But as the role of new pathogenetic
      mechanisms becomes clear, many potential new treatment strategies may become
      available for clinician. 

PMID- 25755320
TI  - Pathophysiology of portal hypertension and its clinical links.
AB  - Portal hypertension is a major cause of morbidity and mortality in patients with
      liver cirrhosis. Intrahepatic vascular resistance due to architectural distortion
      and intrahepatic vasoconstriction, increased portal blood flow due to splanchnic
      vasodilatation, and development of collateral circulation have been considered as
      major factors for the development of portal hypertension. Recently, sinusoidal
      remodeling and angiogenesis have been focused as potential etiologic factors and
      various researchers have tried to improve portal hypertension by modulating these
      new targets. This article reviews potential new treatments in the context of
      portal hypertension pathophysiology concepts. 

PMID- 25755323
TI  - ABCB4 Disease Presenting with Cirrhosis and Copper Overload-Potential Confusion
      with Wilson Disease.
AB  - A 2-year-old female with cirrhosis was found to have a liver copper of 248 MUg/g
      dry weight. She was eventually diagnosed with ABCB4 disease on the basis of
      heterozygote A546D and R176W mutations. Her liver disease was partially
      responsive to ursodeoxycholic acid therapy. Copper overload occurs in cholestatic
      liver disease and this must be considered to avoid misdiagnosis of Wilson
      disease. 

PMID- 25755322
TI  - Hepatocyte transplantation.
AB  - Hepatocyte transplantation (HTx) has been developed for use in liver-based
      metabolic disorders and in acute liver failure. Worldwide, there are around 80
      patients that have been transplanted with hepatocytes. Almost all reported
      studies prove feasibility and safety of the procedure with short- to medium-term
      success. Availability of good quality hepatocytes (HCs) is the main limiting
      factor, and therefore alternative sources of cells such as stem cells are being
      investigated. Other limiting factors include cell engraftment, survival, and
      function of transplanted cells. It remains to be seen if progress in HTx research
      can overcome these hurdles leading to the wider use of the technique as an
      alternative to liver transplantation in the future. 

PMID- 25755321
TI  - Noncirrhotic portal hypertension.
AB  - Portal hypertension is characterized by an increase in portal pressure (> 10
      mmHg) and could be a result of cirrhosis of the liver or of noncirrhotic
      diseases. When portal hypertension occurs in the absence of liver cirrhosis,
      noncirrhotic portal hypertension (NCPH) must be considered. The prognosis of this
      disease is much better than that of cirrhosis. Noncirrhotic diseases are the
      common cause of portal hypertension in developing countries, especially in Asia.
      NCPH is a heterogeneous group of diseases that is due to intrahepatic or
      extrahepatic etiologies. In general, the lesions in NCPH are vascular in nature
      and can be classified based on the site of resistance to blood flow. In most
      cases, these disorders can be explained by endothelial cell lesions, intimal
      thickening, thrombotic obliterations, or scarring of the intrahepatic portal or
      hepatic venous circulation. Many different conditions can determine NCPH through
      the association of these various lesions in various degrees. Many clinical
      manifestations of NCPH result from the secondary effects of portal hypertension.
      Patients with NCPH present with upper gastrointestinal bleeding, splenomegaly,
      ascites after gastrointestinal bleeding, features of hypersplenism, growth
      retardation, and jaundice due to portal hypertensive biliopathy. Other sequelae
      include hyperdynamic circulation, pulmonary complications, and other effects of
      portosystemic collateral circulation like portosystemic encephalopathy. At
      present, pharmacologic and endoscopic treatments are the treatments of choice for
      portal hypertension. The therapy of all disorders causing NCPH involves the
      reduction of portal pressure by pharmacotherapy or portosystemic shunting, apart
      from prevention and treatment of complications of portal hypertension. 

PMID- 25755324
TI  - Auxiliary liver transplantation: a form of gene therapy in selective metabolic
      disorders.
AB  - Auxiliary liver transplantation is an accepted form of therapy in acute liver
      failure and in certain metabolic disorders. We report India's first successful
      auxiliary liver transplantation for Crigler-Najjar syndrome type 1, showing that
      it is technically feasible and safe procedure. It is utmost important to select
      appropriate cases for auxiliary transplant for successful long-term outcome. The
      surgeon should also have an understanding of the portal flow dynamics, as steal
      phenomenon can occur, depriving blood blow to either graft or native liver.
      Though successful in animal models, gene therapy is still in experimental stage
      in humans and pace of progress has been disappointing. Auxiliary liver
      transplantation retains the native liver for future gene therapy. These children
      are young and are likely to have a long life expectancy, and withdrawal of
      immunosuppression would be a huge advantage. 

PMID- 25755325
TI  - Biliary obstruction and a mass lesion in the liver.

PMID- 25755326
TI  - Safety of Complete and Sustained Prophylaxis Withdrawal in Patients Liver
      transplanted for Hepatitis B Virus-related Cirrhosis at Low Risk of Hepatitis B
      Virus Recurrence.
AB  - BACKGROUND: HBV (hepatitis B virus) reactivation after liver transplantation may
      be related to persistence of covalently closed circular (ccc) DNA. We
      investigated the safety of HBV prophylaxis withdrawal in selected HBV
      transplanted patients. METHODS: Thirty patients transplanted 64-195 months
      earlier (23 males, median age 56 years), HBsAg-positive, HBeAg, and HBV-DNA
      negative at transplant (43% HCV/HDV coinfected), with undetectable intrahepatic
      total and ccc-DNA were enrolled. All patients underwent HBIg withdrawal and
      continued lamivudine with monthly HBsAg and HBV-DNA monitoring and sequential
      liver biopsies. Those with confirmed intrahepatic total and ccc-DNA undetect
      ability 24 weeks after stopping HBIg also underwent lamivudine withdrawal and
      were followed up without prophylaxis. RESULTS: Twenty-five patients did not
      exhibit signs of HBV recurrence after prophylaxis withdrawal (median follow-up
      28.7 months, range 22-42). Five patients became HBsAg-positive: one early after
      HBIg withdrawal, the other four after HBIg and lamivudine withdrawal. None of
      these patients experienced clinically relevant events. In the first patient, HBIg
      were reinstituted with prompt HBsAg negativization. Of the other four, one
      remained HBsAg-positive with detectable HBV-DNA and mild alanine transaminase
      elevation and was successfully treated with tenofovir. In the remaining three,
      HBsAg positivity was transient and followed by anti-HBs se-roconversion; thus no
      antiviral treatment was needed. CONCLUSION: Patients with undetectable HBV
      viremia at transplant and no evidence of intrahepatic total and ccc-DNA may
      safely undergo cautious weaning of prophylaxis, showing the low rate of HBV
      recurrence after a 2-year follow-up. Undetectability of intrahepatic ccc-DNA may
      help to identify patients at low risk of recurrence; yet studies with longer
      follow-up are needed.

PMID- 25755327
TI  - Nuclear Factor High-mobility Group Box1 Mediating the Activation of Toll-like
      Receptor 4 Signaling in Hepatocytes in the Early Stage of Non-alcoholic Fatty
      Liver Disease in Mice.
AB  - One of the challenges surrounding nonalcoholic fatty liver disease (NAFLD) is to
      discover the mechanisms that underlie the initiation of it. The aim of this study
      was to elucidate the effects of toll-like receptor 4 (TLR4) signaling in liver
      parenchymal cells during the early stage of NAFLD. Male TLR4-wildtype, TLR4
      knockout, TLR2-knockout, MyD88-knockout, and TRIF-knockout mice were fed a normal
      diet or high-fat diet (HFD). Liver steatosis, alanine aminotrans-ferase levels,
      nuclear translocation of nuclear factor kappa B (NF-kappaB) (P65), macrophage
      accumulation, and neutrophil infiltration were assessed. Using Kupffer cell
      depletion or bone-marrow transplantation, we examined the potential role of
      Kupffer cells and myeloid infiltrating cells during the initiation of NAFLD.
      Immunohistochemistry and western blotting were implemented to determine the
      release of high-mobility group box1 (HMGB1). The neutral antibody against HMGB1
      was used to block the activity of free HMGB1. Here, we report that the activation
      of TLR4 signaling in hepatocytes, accompanied with the relocation of P65 in
      nucleus, was proven to play an important role during the initiation of NAFLD.
      Importantly, HMGB1 releasing from hepatocytes in response to free fatty acid
      (FFA) infusion was first reported as the key molecule for the TLR4/MyD88
      activation and cytokines expression in vitro and in vivo. Treatment with
      neutralizing antibody to HMGB1 protects against FFA-induced tumor necrosis factor
      alpha and interleukin-6 production. CONCLUSION: Our study supports the notion
      that TLR4/MyD88 signaling in liver parenchymal cells plays a pivotal role during
      the early progression of HFD-induced NAFLD, in which free HMGB1 served as a
      positive component mediating TLR4 activation.

PMID- 25755329
TI  - Hepatobiliary quiz-2 (2011).

PMID- 25755328
TI  - Biliary obstruction and a mass lesion in the liver: intrabiliary rupture of
      hepatic hydatid cyst.

PMID- 25755330
TI  - 1 colonic bleed after liver transplantation due to mucormycosis-a case report and
      review of literature.

PMID- 25755331
TI  - 2 prolonged weaning following liver transplant-a case report.

PMID- 25755332
TI  - 4 postoperative changes in coagulation parameters in 105 patients undergoing live
      donor hepatectomies-implications for epidural analgesia.

PMID- 25755333
TI  - 3 ANESTHETIC MANAGEMENT OF LIVER TRANSPLANTATION FOR FACTOR VII DEFICIENCY IN A 6
      MONTH-OLD CHILD-THROMBOELASTOGRAPHY-GUIDED INTRA-OPERATIVE REPLACEMENT OF
      RECOMBINANT FACTOR VIIa.

PMID- 25755334
TI  - 6 tuberculosis and living donor liver transplantation-a 7-year experience from
      India.

PMID- 25755335
TI  - 5 comparison of clinical prognostic indicators (cpi) with model for end-stage
      liver disease (meld) and king's college hospital (kch) criteria for mortality
      prediction in acute liver failure.

PMID- 25755336
TI  - 7 acute liver failure in giant cell hepatitis-successful adult-to-adult right
      lobe living-related liver transplantation.

PMID- 25755337
TI  - 8 successful thrombolysis of early asymptomatic hepatic artery thrombosis after
      right lobe adult-to-adult living-related liver transplantation.

PMID- 25755338
TI  - 9 living-related liver-transplant donor with hypercoaguable state-a case report
      and suggested workup.

PMID- 25755339
TI  - 10 donor hepatectomy in a postatrial septal defect repair patient-implications
      for the anesthetist and surgeon.

PMID- 25755340
TI  - 11 reduced left lateral sector liver transplantation in children under 10 kg-less
      is better.

PMID- 25755341
TI  - 12 variations in live-liver donor hilar anatomy and classification of donors
      based on anatomic suitability.

PMID- 25755342
TI  - 13 which is better? Duct-to-duct/hepaticojejunostomy/both-in a right lobe graft
      with two ducts in adult living-related liver transplantation.

PMID- 25755343
TI  - 14 right posterior sectoral graft procurement is always possible if right
      posterior sectoral portal vein can be divided extrahepatically.

PMID- 25755344
TI  - 15 comparison of transfusion requirements between deceased donor liver
      transplantation and living donor liver transplantation-single center's
      experience.

PMID- 25755345
TI  - 16 an unusual case for liver transplantation in a child.

PMID- 25755346
TI  - 17 an evaluation of the donor profiles and outcomes of donors in living donor
      liver transplant (ldlt).

PMID- 25755347
TI  - 18 early postoperative mortality in recipients following deceased donor liver
      transplantation (ddlt)-a clinical profile.

PMID- 25755348
TI  - 19 cost of immunosuppression using generic products after liver transplantation.

PMID- 25755349
TI  - 20 predictors for need for liver transplants in acute zinc phosphide poisoning.

PMID- 25755350
TI  - 21 challenges in liver transplantation for acute hepatic failure.

PMID- 25755351
TI  - 22 vascular complications in living donor pediatric liver transplant (ldlt).

PMID- 25755352
TI  - 23 postliver biopsy arterioportal fistula in living donor liver transplant-a case
      report.

PMID- 25755353
TI  - 26 bilirubin as a predictor of early mortality after liver transplantation.

PMID- 25755354
TI  - 24 extra-anatomic hepatic artery reconstruction in deceased donor.

PMID- 25755355
TI  - 25 compression of the inferior vena cava due to congested liver during deceased
      donorliver transplantation.

PMID- 25755356
TI  - 28 single center experience on living donor liver transplantation in children.

PMID- 25755357
TI  - 27 transfusion predictors in pediatric liver transplantation-single center's
      experience.

PMID- 25755358
TI  - 30 excellent outcome of living donor liver transplantation in patients with
      hepatopulmonary syndrome-a single center experience.

PMID- 25755359
TI  - 29 cladophialophora bantiana causing brain abscess following liver transplant-a
      case report.

PMID- 25755360
TI  - 31 laparoscopic cystopericystectomy.

PMID- 25755361
TI  - 33 hepatic resection in children-twenty-one cases.

PMID- 25755362
TI  - 32 portal vein thrombus irradiation-an alternative in inoperable hepatocellular
      carcinoma.

PMID- 25755363
TI  - 35 etiology of renal dysfunction in cirrhosis.

PMID- 25755364
TI  - 34 cystopericystectomy-patient selection is essential.

PMID- 25755365
TI  - 37 retrospective study of isolated hepatic injury.

PMID- 25755366
TI  - 38 hepatic resection-scope for general surgeon!

PMID- 25755367
TI  - 36 prevalence of hepatitis e virus infection among pregnant women in rajasthan.

PMID- 25755369
TI  - 39 hepatocellular carcinoma-revising treatment option!

PMID- 25755368
TI  - 40 comparison of cusa and kelly's clamp crush technique as liver parenchymal
      techniques in liver resection.

PMID- 25755370
TI  - 41 resection or transplantation for early hepatocellular carcinoma in a cirrhotic
      liver-size does matter.

PMID- 25755371
TI  - 42 right hepatectomy as a model for assessing the risk of major liver resection-a
      comparison over two consecutive decades.

PMID- 25755372
TI  - 44 hepatic steatosis-quantification by non-enhanced ct scan.

PMID- 25755373
TI  - 43 a prospective study about etiology of chronic liver diseases, nature of acute
      hepatic assaults, clinical course, and prognosis of patients with acute-on
      chronic liver failure in bangladesh.

PMID- 25755374
TI  - 45 25 gram versus 50 gram of 25% albumin in preventing renal impairment after
      large volume paracentesis in cirrhosis.

PMID- 25755375
TI  - 46 predictors of health-related quality of life in patients with liver cirrhosis
      at tertiary care hospital, karachi.

PMID- 25755376
TI  - 47 spectrum of liver disease and experience of liver resection in bangabandhu
      sheikh mujib medical university (bsmmu) and prospects of liver transplantation in
      bangladesh.

PMID- 25755377
TI  - 48 a prospective audit of one-hundred patients presenting for thoracic epidural
      pain relief for hepatobiliary surgery.

PMID- 25755380
TI  - The Green Tea Polyphenol, Epigallocatechin-3-Gallate (EGCG)-One Step Forward in
      Antiviral Therapy Against Hepatitis C Virus.

PMID- 25755379
TI  - Hepatobiliary quiz-2 (2011).

PMID- 25755381
TI  - Predicting Mortality Across a Broad Spectrum of Liver Disease-An Assessment of
      Model for End-Stage Liver Disease (MELD), Child-Turcotte-Pugh (CTP), and
      Creatinine-Modified CTP Scores.
AB  - BACKGROUND/AIMS: The role of model for end-stage liver disease (MELD) among
      Indian patients with cirrhosis is uncertain. We studied and compared MELD with
      Child-Turcotte-Pugh (CTP) and creatinine-modified-CTP (CrCTP) scores for
      predicting 1-, 3-, and 6-months mortality. METHODS: One-hundred and two patients
      with cirrhosis were studied. The CrCTP was calculated by adding creatinine score
      of 0, 2 and 4 with creatinine levels of <=1.2mg/dL, 1.3-1.8 mg/dL and >=1.9mg/dL,
      respectively to CTP score. Survival curves were plotted and receiver operating
      characteristics (ROC) curves were used to compare the scores. Predictors of
      mortality were analyzed using Cox proportional hazards model. RESULTS: Scores of
      CTP, CrCTP, and MELD have excellent diagnostic accuracy for predicting mortality
      (c-statistics >0.85). The MELD was superior to CTP for predicting 3-months [c
      statistic and 95% confidence interval, 0.967 (0.911-0.992) vs 0.884 (0.806
      0.939)] and 6-months [0.977 (0.925-0.996) vs 0.908 (0.835-0.956)] mortality
      (P=0.05), while CrCTP [0.958 (0.899-0.988)] was better than CTP for predicting 3
      months mortality (P=0.02). Serum creatinine (hazard ratio 4.43, P<0.0001) is a
      strong independent predictor of mortality. CONCLUSION: The MELD accurately
      predicts mortality in cirrhosis and is better than CTP for predicting the short
      term and intermediate-term mortality. Adding serum creatinine to CTP though
      significantly improves its diagnostic accuracy for short-term mortality; however,
      it remains lower than MELD alone.

PMID- 25755382
TI  - Progression of noncirrhotic portal hypertension in a pediatric population.
AB  - BACKGROUND/OBJECTIVES: The optimal management of children with noncirrhotic
      portal hypertension is controversial. Some groups suggest early and aggressive
      surgical intervention, while others report long-term success with conservative
      management. METHODS: We conducted a retrospective study of 26 patients with
      noncirrhotic portal hypertension treated at our institution. We compared platelet
      counts, white blood cell (WBC) counts, spleen size, hospital admissions,
      gastrointestinal bleeds, and longitudinal trends of specific clinical parameters
      using standard univariate and time-trend analytic techniques. RESULTS: Mean age
      at the time of diagnosis was 5.2 years. Portal vein thrombosis was found in 84.6%
      of patients (n=22). There was one mortality related to malignancy. There was not
      a progression of hypersplenism in patients that did not receive a shunt and
      conversely, we did not notice a significant decrease in spleen size following
      shunt surgery (P=0.2). Platelet and WBC counts trended downward among patients
      managed medically, while platelets increased and WBC counts remained stable in
      surgical patients. There was a significant decrease in hospital admissions for
      gastrointestinal bleeding following surgical intervention in the shunt group
      compared with nonshunt (P=0.0009). CONCLUSION: While our analysis was limited
      given small sample sizes and selection bias, it suggests that the majority of
      pediatric patients with noncirrhotic portal hypertension will do well long-term
      without surgical intervention.

PMID- 25755383
TI  - Cutaneous manifestations of common liver diseases.
AB  - Skin functions as a window to our overall health and a number of systemic
      diseases result in various cutaneous changes. Knowledge of these manifestations
      helps in suspecting an underlying systemic illness. Cutaneous abnormalities are
      quite common in patients with liver diseases and this article aims to focus on
      these dermatoses. Cutaneous manifestations seen in patients with liver disease
      though common are nonspecific. They can also be seen in patients without liver
      diseases and generally do not indicate about a specific underlying hepatic
      disorder. The presence of a constellation of signs and symptoms is more useful in
      pointing toward an underlying hepatobiliary condition. The commonest symptom in
      patients with liver disease is pruritus which is often protracted and disabling.
      Other common features include spider angiomas, palmar erythema, paper money skin,
      xanthelasmas, pigmentary changes, and nutritional deficiencies. In this article,
      first the common cutaneous manifestations that may be associated with liver
      disorders are discussed and then common liver diseases with their specific
      cutaneous findings are discussed. Cutaneous abnormalities may be the first clue
      to the underlying liver disease. Identifying them is crucial for early diagnosis
      and better management. 

PMID- 25755384
TI  - Occult hepatitis C virus infection and its relevance in clinical practice.
AB  - Hepatitis C virus (HCV) can persist in the liver, lymphoid (immune) cells, and
      serum of individuals long after an apparently complete therapy-induced or a
      spontaneous resolution of hepatitis C. This essential asymptomatic infection,
      called secondary occult HCV infection (OCI), usually occurs in anti-HCV antibody
      reactive individuals with normal liver function tests. This infection has been
      identified when the nucleic acid amplification assays of enhanced sensitivity
      were applied for the detection of HCV genome and its replication. In addition to
      the secondary OCI, a form of low-level HCV-RNA-positive infection of unknown
      etiology coinciding with moderately elevated serum liver enzymes and progressing
      in the absence of anti-HCV detectable by standard clinical assays has been
      reported. Because of its undefined origin, it can be termed cryptogenic OCI. In
      this review, the general characteristics of OCI, the ways of its detection and
      associated controversies, and the potential clinical implications of its
      existence will be concisely outlined. 

PMID- 25755386
TI  - Evaluation of liver transplant recipients.
AB  - The outcome of liver transplantation (LT) is dependent on many factors including
      graft quality, surgical techniques, postoperative care, immunosuppressive
      regimens and most importantly, careful pre-transplant recipient evaluation and
      selection. Currently, the expected 1-year and 5-year survival rates after LT are
      85-95% and 75-85%, respectively. The improvement in outcomes and better awareness
      has resulted in an increasing demand for LT around the world including India.
      Transplant physicians have responded to this increased demand by developing
      several strategies including the use of older donors, grafts from hepatitis C
      positive donors or those with previous hepatitis B infection (positive hepatitis
      B virus [HBV] core immunoglobulin G [IgG] antibody), graft from nonheart beating
      donors, domino transplantation (liver from patients with familial amyloid
      polyneuropathy transplanted into older recipients), split-liver grafts, and live
      donor liver transplant (LDLT). Currently, the only treatment that prolongs
      survival in those with end-stage acute or chronic liver failure is
      transplantation of either partial or full liver donor graft. Because of the
      enormous disparity in supply and demand for donor organs, costs, and potential
      morbidity and mortality of live donors in LDLT, it has become incumbent on the
      transplant community to ration the available organs in a way that provides the
      best outcomes and in the process, serves the best interest of the population as a
      whole. When evaluating a potential candidate for LT, it is imperative to
      determine whether the recipient is going to benefit from the procedure
      immediately and in the long-term. In this review, we will discuss the process of
      selection and optimal evaluation of potential LT recipients. 

PMID- 25755385
TI  - Nutritional status and liver transplantation.
AB  - Chronic liver disease has a profound effect on nutritional status and
      undernourishment is almost universally present in patients with end-stage liver
      disease undergoing liver transplantation. In the last decades, due to
      epidemiological changes, a trend showing an increase in patients with end-stage
      liver disease and associated obesity has also been reported in developed
      countries. Nutrition abnormalities may influence the outcome after
      transplantation therefore, the importance to carefully assess the nutritional
      status in the work-up of patients candidates for liver transplantation is widely
      accepted. More attention has been given to malnourished patients as they
      represent the greater number. The subjective global nutritional assessment and
      anthropometric measurements are recognized in current guidelines to be adequate
      in identifying those patients at risk of malnutrition. Cirrhotic patients with a
      depletion in lean body mass and fat deposits have an increased surgical risk and
      malnutrition may impact on morbidity, mortality and costs in the post
      transplantation setting. For this reason an adequate calorie and protein intake
      should always be ensured to malnourished cirrhotic patient either through the
      diet, or using oral nutritional supplements or by enteral or parenteral nutrition
      although studies supporting the efficacy of nutritional supplementation in
      improving the clinical outcomes after transplantation are still scarce. When
      liver function is restored, an amelioration in the nutritional status is
      expected. After liver transplantation in fact dietary intake rapidly normalizes
      and fat mass is progressively regained while the recovery of muscle mass can be
      slower. In some patients unregulated weight gain may lead to over-nutrition and
      may favor metabolic disorders (hypertension, hyperglycemia, hyperlipidemia). This
      condition, defined as 'metabolic syndrome', may play a negative role on the
      overall survival of liver transplant patients. In this report we review data on
      nutrition and liver transplantation. 

PMID- 25755387
TI  - Mutation Analysis in Crigler-Najjar Syndrome Type II-Case Report and Literature
      Review.
AB  - Crigler-Najjar syndrome (CN) is a congenital defect in bilirubin conjugation due
      to complete or partial deficiency of uridine 5'-diphosphate
      glucuronosyltransferase (UGT). It is of two types: CN type I and CN type II.
      Patients with CN type II present with indirect hyperbilirubinemia in adulthood.
      We report a CN type II with homozygous mutation in UGT1A1 gene. This is the first
      case report of mutation analysis in CN type II from India. 

PMID- 25755389
TI  - Spontaneous perforation of gallbladder with intrahepatic bilioma.
AB  - Spontaneous perforation of gallbladder is uncommon. We report a rare case of
      perforation of the gallbladder due to gallstone disease with formation of a large
      intrahepatic bilioma. The patient was managed conservatively with percutaneous
      drainage of the intrahepatic collection followed by endoscopic retrograde
      cholangiopancreatography (ERCP) and cholecystectomy. 

PMID- 25755388
TI  - Atypical presentation of cytomegalovirus infection in a liver transplant patient.
AB  - Cytomegalovirus (CMV) is the most common viral infection in solid organ
      transplant recipients. Symptomatic infection usually presents with fever,
      pneumonia, colitis, or cytopenia. We describe a case of symptomatic CMV infection
      in a liver transplant recipient presenting with atypical symptoms of only
      persistent nausea and vomiting, in the absence of classical symptoms and signs;
      thus, highlighting the importance of high index of suspicion of CMV in
      immunocompromised patients, keeping in mind the high morbidity and mortality
      associated with this disease. 

PMID- 25755390
TI  - Recent onset dyspnea in a patient with cirrhosis of liver.

PMID- 25755392
TI  - Multiple choice questions.

PMID- 25755391
TI  - Hepatology elsewhere.

PMID- 25755393
TI  - Recent onset dyspnea in a patient with cirrhosis of liver.

PMID- 25755394
TI  - Answers to multiple choice questions.

PMID- 25755397
TI  - Journal of Clinical and Experimental Hepatology (JCEH): Well Begun is Half-done.

PMID- 25755398
TI  - The Outgoing President of INASL: An Officer, an Academician and a Gentleman.

PMID- 25755399
TI  - Back from the future: treating hepatitis C virus with conventional interferon.

PMID- 25755400
TI  - Battle in Search for Simple Reliable Non-invasive Marker of Liver Fibrosis.

PMID- 25755401
TI  - Treatment of Chronic Hepatitis due to Hepatitis C Virus (CH-C) in India: A
      Randomized Controlled Trial Comparing Daily Interferon-alfa-2b and Ribavirin with
      Daily Interferon-alfa-2b and Glycyrrhizin-A Multicenter Study.
AB  - BACKGROUND AND AIM: Pegylated-interferon-alfa (PEG-IFN-alpha) with ribavirin is
      an established treatment in chronic hepatitis due to hepatitis C virus (HCV) (CH
      C). Such treatment is expensive and in resource-poor countries such as India,
      alternative less expensive therapy is needed. METHODS: Multicenter randomized
      controlled trial comparing two treatment regimens (interferon-alfa-2b [IFN-alpha
      2b] 3 million unit/day [MU/day] and ribavirin 1000 mg/day [I+R] vs IFN-alpha-2b 3
      MU/day and glycyrrhizin 250 mg [I+G]) in CH-C. Viral, host characteristics and
      therapeutic responses were assessed (ICMR-6 months trial for chronic hepatitis
      CTRI/2008/091/000105). RESULTS: One hundred and thirty-one patients meeting the
      inclusion criteria were randomized to I + G (n=64) or I+R (n=67) during the
      period February 2002 to May 2005. About 85% (I+G=53, I+R=58) completed 6 months
      of treatment and 89% of them (I+G=46, I+R=53) completed 6 months of follow-up
      after completion of treatment. Hepatitis C virus genotype 3 was the major type
      detected (71% patients). The mean log10 viral load (copies/mL), histological
      activity index, and fibrosis stage for all patients were 5.1 +/- 0.98, 5 +/- 2,
      and 2+/- 1.5, respectively. Sustained viral response (SVR) was significantly
      higher in I + R group than in I + G group (65.7% vs 46.9%, OR=2.2, P = 0.03).
      Treatment with I + G was associated with significantly lower frequencies of
      leukopenia (2% vs 17%, P <0.01) and anemia (8% vs 40%, P <0.001) as compared to
      treatment with I + R. CONCLUSION: Genotype 3 HCV infection with low viral load is
      prevalent in India. Daily IFN with ribavirin showed significantly better
      responses. Leukopenia and anemia were significantly more in ribavirin group.
      Responses observed with IFN + ribavirin were similar to the reported response
      rates with PEG-IFN suggesting that this modality may be considered as a cheaper
      alternative of treatment for chronic hepatitis C.

PMID- 25755403
TI  - Human Interferon Regulatory Factor 2 Gene Expression is Induced in Chronic
      Hepatitis C Virus Infection-A Possible Mode of Viral Persistence.
AB  - BACKGROUND: The interferon regulatory factors (IRFs) are a family of
      transcription factors known to be involved in the modulation of cellular
      responses to interferons (IFNs) and viral infection. While IRF-1 acts as a
      positive regulator, IRF-2 is known to repress IFN-mediated gene expression. The
      increase in the IRF-1/IRF-2 ratio is considered as an important event in the
      transcriptional activation of IFN-alpha gene toward development of the cellular
      antiviral response. OBJECTIVE: This study was performed to assess the expression
      of IRF mRNAs along with the expression level of IFN-alpha, its receptor (IFNAR
      1), and the signal transduction factor (STAT-1) in treatment naive hepatitis C
      virus (HCV)-infected subjects. MATERIALS: Thirty-five chronically infected (CHC)
      patients and 39 voluntary blood donors as controls were included in the study.
      Quantification of HCV-RNA (ribonucleic acid) and genotyping were done by real
      time polymerase chain reaction (PCR) and hybridization assays, respectively,
      using patient's serum/plasma. In both controls and patients, the serum level of
      IFN-alpha and IFN-alpha was measured by flow cytometry. Target gene expressions
      were studied by retro-transcription of respective mRNAs extracted from peripheral
      blood mononuclear cells (PBMCs) followed by PCR amplification and densitometry.
      Minus-strand HCV-RNA as a marker of viral replication in PBMCs was detected by an
      inhouse PCR assay. RESULTS: Both IRF-1 and IRF-2 genes were significantly
      enhanced in CHC than in control subjects (P < 0.001). A significant positive
      correlation (r (2) = 0.386, P <0.01) was obtained between higher IRF-2 gene
      expression and increasing level of HCV-RNA. Chronically infected subjects (13%)
      harboring replicating HCV in PBMCs showed no significant differences in gene
      expressions than the subjects without HCV in PBMCs. CONCLUSION: Our findings
      indicate that HCV modulates host immunity by inducing IRF-2 gene to counteract
      IRF-1-mediated IFN-alpha gene expression. Since the IRF-2 gene is known to encode
      oncogenic protein, the role of IRF-2 in CHC patients developing hepatocellular
      carcinoma warrants further studies.

PMID- 25755402
TI  - Comparison of circulating endothelial cell/platelet count ratio to aspartate
      transaminase/platelet ratio index for identifying patients with cirrhosis.
AB  - BACKGROUND/OBJECTIVES: Circulating endothelial cells (CECs) are indicative of
      vascular injury and correlate with severity of vascular diseases. A pilot study
      showed that the ratio of CEC to platelet count (CEC/PC) was effective in
      predicting cirrhosis. Therefore, we evaluated CEC/PC in a larger cohort of
      patients, correlated it with cirrhosis, and compared its operating
      characteristics with previously described biomarker for cirrhosis, the
      AST/platelet ratio index (APRI). METHODS: Fifty-three patients with cirrhosis, 20
      matched healthy controls, and 9 patients with noncirrhotic liver disease were
      recruited. Peripheral blood sample was collected and analyzed to enumerate
      nucleated CEC CD146+, CD105+, CD45- using a commercial assay. RESULTS: Median CEC
      counts were significantly higher in patients with cirrhosis (62 cells/4 mL,
      interquartile range [IQR]: 43.5-121) as compared with controls (31 cells/4 mL,
      IQR: 22.2-40). The CEC/PC was also significantly elevated in cirrhotics (0.69,
      IQR: 0.39-1.48) compared with controls (0.12, IQR: 0.09-0.20) and noncirrhotics
      (0.21, IQR: 0.08-0.43). Receiver operator characteristic (ROC) analysis revealed
      that CEC cutoff value of >=37 cells/4 mL showed sensitivity of 81% and
      specificity of 75% for differentiating cirrhosis from controls (area under the
      curve [AUC]: 0.80; 95% confidence interval [CI] 0.67-0.91). The CEC/PC ratio
      cutoff value of >=0.23 showed sensitivity of 91% and specificity of 82% (AUC:
      0.92; 95% CI 0.83-0.99). The APRI cutoff value of >=0.4 showed sensitivity of 94%
      and specificity of 85% for differentiating cirrhosis from control patients (AUC:
      0.96; 95% CI 0.90-1.0). A product of CEC and APRI, termed CAPRI (CEC-APRI),
      effectively distinguished patients with cirrhosis from controls; with cutoff
      value of >=12.7, showing higher sensitivity of 98% and specificity of 85% (AUC:
      0.98; 95% CI 0.96-1.0). CONCLUSION: The CEC/PC ratio is significantly elevated in
      patients with cirrhosis and demonstrates comparable operating characteristics to
      previously described APRI. Furthermore, CAPRI, compiled as product of CEC to APRI
      showed outstanding ability to distinguish patients with cirrhosis from controls,
      although larger studies are necessary for validation.

PMID- 25755404
TI  - Perioperative bacterial infections in deceased donor and living donor liver
      transplant recipients.
AB  - BACKGROUND: Deceased donor (DDLT) and living donor (LDLT) liver transplant (LT)
      is in vogue in several centers in India. Most centers are resorting to LDLT as a
      preferred surgery due to shortage of deceased donor liver. The risk of infection
      and its effect on survival in both groups of recipients from the Indian
      subcontinent are not known. The study was conducted to compare the bacterial
      infection rates among LDLT and DDLT recipients and their impact on survival at a
      tertiary referral center. METHODS: Retrospective data on 67 LT recipients were
      reviewed. Data on pre-, per-, and postoperative bacterial infection rates and the
      common isolates were obtained. RESULTS: Thirty-five patients had LDLT and 32 had
      DDLT. The prevalence of pre-operative bacterial infection and the isolates was
      similar in both groups. The perioperative bacterial infection rates were
      significantly higher in DDLT recipients (P < 0.01) (relative risk: 1.44 95%
      confidence interval 1.04-1.9). In both LDLT and DDLT, the common source was
      urinary tract followed by bloodstream infection. The common bacterial isolates in
      either transplant were Klebsiella followed by Escherichia coli, Pseudomonas spp.
      and nonfermenting gram-negative bacteria. Six patients (four LDLT; two DDLT) were
      treated for tuberculosis. Among the risk factors, cold ischemic time, and
      duration of stay in the intensive care unit was significantly higher for DDLT (p
      < 0.01). The death rates were not significantly different in the two groups.
      However, the odds for death were significantly high at 26.8 (p < 0.05) for
      postoperative bacterial infection and 1.8 (p < 0.001) for past alcohol.
      CONCLUSION: Liver transplant recipients are at high-risk for bacterial infection
      irrespective of type of transplant, more so in DDLT.

PMID- 25755405
TI  - A pharmacological profile of ribavirin and monitoring of its plasma concentration
      in chronic hepatitis C infection.
AB  - Chronic hepatitis C (CHC) infection, usually an asymptomatic infection, has long
      term serious complications such as cirrhosis, hepatocellular carcinoma, and end
      stage liver disease requiring liver transplantation (LT). Several novel drugs
      against hepatitis C which form part of 'specifically targeted antiviral therapy
      for hepatitis C' (STAT-C) have been developed. These include NS3/4A protease
      inhibitors telaprevir, boceprevir, and nucleoside/non-nucleoside polymerase
      inhibitors (NS5A) which hold promise for future therapy. Despite the development
      of new anti-hepatitis C virus (HCV) drugs, ribavirin (RBV) remains the single
      most important drug to prevent relapse and is frequently included among newer
      regimens being developed with novel small molecule anti-HCV drugs. The current
      approved treatment is a combination therapy of once weekly subcutaneous pegylated
      interferon (PEG-IFN)-alpha plus body-weight-based oral RBV regimen. The most
      significant dose-dependent side effect of RBV is hemolytic anemia warranting dose
      reduction or discontinuation in severe cases compromising sustained virological
      response (SVR). Monitoring RBV plasma concentration has been challenging due to
      its peculiar pharmacokinetics and has been done to predict both efficacy and
      toxicity. Herein, we review the pharmacological profile of RBV and the monitoring
      of its plasma concentration, monitoring in renal impairment, post-LT, and human
      immunodeficiency virus (HIV)-HCV co-infection in patients being treated with
      combination therapy of PEG-IFN-alpha and RBV. 

PMID- 25755407
TI  - Endoscopic Ultrasound (EUS) for Esophageal and Gastric Varices: How Can it
      Improve the Outcomes and Reduce Complications of Glue Injection.
AB  - A large part of portal venous system and the paragastric and para-esophageal
      collateral circulation is within the reach of endoscopic ultrasound (EUS). The
      EUS is more sensitive than gastroscopy for the detection of gastric varices (GV),
      and can accurately distinguish GV from thickened gastric folds. Gastric varices
      are depicted by serpiginous, anechoic, Doppler-positive mural channels, with
      larger collateral channels visible outside the gastric wall. The EUS has also
      been used to monitor the completeness of GV obturation after glue injection.
      There are limited data that this strategy may be clinically beneficial to prevent
      GV re-bleed. The EUS has been used to deliver glue injections under real-time
      monitoring into the vascular channels, with or without steel coils as scaffolding
      for the glue. The potential advantages of this technique include a straight scope
      position, lack of hindrance from pooled blood in gastric fundus, smaller glue
      volume requirements, and precise intra-vascular placement of glue with avoidance
      of intramural injections, and reduced embolic complications. 

PMID- 25755406
TI  - Gluing gastric varices in 2012: lessons learnt over 25 years.
AB  - Bleeding from gastric varices (GV) continues to pose a challenge to the
      endoscopist and no consensus has been reached on the best way for treating these
      patients. Gastric variceal obturation (GVO) with the tissue adhesive, N-2-butyl
      cyanoacrylate (NBC), is considered the treatment of first-choice for this
      condition in most parts of the world. The liquid monomer polymerizes into a solid
      cast, obturating the vessel within 10-20 s of coming in contact with ionic
      solutions such as blood. Gastric variceal obturation achieves hemostasis in over
      90% of patients with active bleeding, eradicates GV in over 80% of these
      patients, and re-bleeding occurs in 3-30%. These results are comparable with
      those of transjugular intrahepatic portosystemic shunting (TIPS; over 90%
      hemostasis in acute bleeding with re-bleeding in 15-30%). Though, there has been
      no direct comparison with GVO, balloon-occluded retrograde transvenous
      obliteration of GV (BRTO) achieves near 100% obliteration with recurrence in 0
      10% and is superior to TIPS for hemostasis in active bleeding when used in
      combination with transcatheter sclerotherapy. Several complications have been
      described for GVO including thromboembolic complications which occur in 0.5-4.3%
      and may be devastating in some. Many of the complications and the variability in
      results of GVO can be attributed to variations in injection technique. The use of
      a standardized injection technique has been reported to achieve 100% hemostasis
      and obliteration with 6.9% re-bleeding and no embolic complications. Gastric
      variceal obturation with NBC continues to be the first-choice therapy for GV
      bleeding outside Japan. Adherence to a standard injection technique will maximize
      hemostasis and eradication of GV while minimizing complications of therapy. 

PMID- 25755408
TI  - HBsAg Quantification in Clinical Practice.
AB  - Several standardized commercial assays for quantification of hepatitis B surface
      antigen (qHBsAg) are now available. Studies on HBsAg kinetics from Asia and
      Europe have demonstrated that HBsAg levels are highest during the immune-tolerant
      phase, become lower during immune-clearance phase and are the lowest in hepatitis
      B 'e' antigen (HBeAg)-negative inactive low-replicative phase with a rise during
      HBeAg-negative chronic hepatitis B (CHB). Combined use of hepatitis B virus
      deoxyribonucleic acid (HBV-DNA) and HBsAg levels may help in differentiating true
      inactive carrier state from HBeAg-negative CHB. Several retrospective studies
      have demonstrated a role for decline in HBsAg level for predicting response and
      nonresponse to therapy. In HBeAg-positive patients treated with pegylated
      interferon (PEG-IFN), a lack of decline of qHBsAg at week 12 predicts
      nonresponders while a decline of qHBsAg at week 24 predicts responders to PEG
      IFN. In HBeAg-negative patients, if at week 12, there is no decline in qHBsAg and
      the HBV-DNA decline is < 2 log, the patient is unlikely to respond, then stopping
      of PEG-IFN should be considered. With nucleos(t)ide analogs, the decline in HBsAg
      is lower than that with PEG-IFN and more marked in patients with HBeAg-positive
      chronic hepatitis, with elevated alanine aminotransaminase (ALT), thus suggesting
      that active immune response against HBV is required to lower HBsAg. In patients
      with HBeAg-negative chronic hepatitis, fall in HBsAg may help in developing
      stopping rules to reduce the need for lifelong therapy. Information provided by
      HBsAg is complementary to HBV-DNA and cannot replace the same. Prospective
      studies on HBsAg kinetics from all regions of the world are required to define
      optimum time of testing and cutoff levels before stopping rules can be
      recommended. 

PMID- 25755409
TI  - Post-liver Transplant Biliary Complications.
AB  - Biliary tract complications remain a common source of morbidity and mortality in
      liver transplant (LT) recipients with an estimated incidence of 5-30% after
      orthotopic LT and a mortality rate of up to 10%. Biliary complications after LT
      may be related to various factors including hepatic artery thrombosis or
      stenosis, ischemia reperfusion injury, immunologic injury, infections, donor
      pool, and technical issues which include imperfect anastomosis and T-tube-related
      complications. Management of the detected biliary complications includes
      nonsurgical and surgical methods. A majority of these post transplant biliary
      complications can be treated with endoscopic retrograde cholangiography. If
      unsuccessful, a percutaneous intervention or surgery may be required. In this
      article, we review the incidence, clinical presentation, and management of the
      main types of biliary complications. 

PMID- 25755410
TI  - Onset of Type 1 Diabetes Mellitus During Pegylated-interferon Alfa and Ribavirin
      Therapy for Chronic Hepatitis C Virus Infection.
AB  - A 16-year-old female was treated with pegylated-interferon (PEG-IFN) alfa (a)-2b
      and ribavirin combination therapy for chronic hepatitis C virus (HCV) infection.
      She attained rapid virological response. She presented with diabetic ketoacidosis
      after 41 weeks of therapy. Anti-glutamic acid decarboxylase antibodies and islet
      cell antibodies were negative. Her fasting serum C-peptide level was <0.1 ng/mL,
      and the treatment course was completed. This case underlines the importance of
      periodic plasma glucose monitoring in patients during and after PEG-IFN and
      ribavirin therapy. 

PMID- 25755411
TI  - Association of Bell's Palsy with Hepatitis E Virus Infection: A Rare Entity.
AB  - Hepatitis E virus (HEV) infection is a common cause of acute hepatitis in India
      and other developing countries. The data regarding the neurologic manifestation
      of HEV infection are limited. The neurologic disorders including Guillain-Barre
      syndrome, polyradiculopathy, neuralgic amyotrophy, encephalitis, bilateral
      brachial neuritis, ataxia/proximal myopathy, and acute transverse myelitis have
      been described. Bell's palsy and other cranial nerve involvement in hepatitis A
      virus (HAV) and HEV infection are rare. We present the second case of Bell's
      palsy associated with HEV. 

PMID- 25755412
TI  - Hepatocellular carcinoma presenting as budd-Chiari syndrome.

PMID- 25755413
TI  - Multiple choice questions.

PMID- 25755414
TI  - It is Patatin-like Phospholipase Domain-containing 3 Gene (PNPLA3)-All the Way.

PMID- 25755416
TI  - Non-alcoholic Fatty Liver Disease Progression: All Depends on the Inflammasome
      Deficiency Driven Dysbiosis.

PMID- 25755415
TI  - Answers to multiple choice questions.

PMID- 25755417
TI  - The New INASL President: Brilliant and Articulate.

PMID- 25755418
TI  - Microsomal Epoxide Hydrolase Polymorphisms and Haplotypes as Determinants of
      Hepatitis B Virusand Hepatitis C Virus-related Liver Disease in Indian
      Population.
AB  - BACKGROUND: Hepatocellular carcinoma (HCC) is the fifth most common cancer and
      third leading cause of death worldwide. Main causes of HCC are hepatitis B virus
      (HBV) and hepatitis C virus (HCV) infections. mEPHX, a xenobiotic metabolizing
      enzyme, exhibits a dual role of procarcinogen detoxification and activation,
      hence considered as a cancer risk factor as well as a protective factor. Two
      known polymorphic forms of mEPHX, exon in exon 3 and 4, are associated with the
      development of HCC. OBJECTIVE: To determine the association of genotypes and
      haplotypes of mEPHX with risk of HCC developments separately in HBV- and HCV
      infected carriers and patients with hepatitis. METHODS: Polymerase chain
      reactions (PCR) were carried out using primers to amplify exon 3 (113 Tyr->His
      variant) and exon 4 (139 His->Arg) polymorphic sites. To distinguish the wild and
      variant forms, PCR amplification products were digested with restriction
      endonucleases EcoRV and Rsa1 for exons 3 and 4, respectively. RESULT: Exon 3
      genotypes, Y113H and H113H, shared a protective association with HBV-chronic
      hepatitis infection (P < 0.001 and P< 0.01, respectively) as well as HBV-HCC
      development (P < 0.001) among HBV-carrier group, while Y113H acts as a risk
      factor for HCV-chronic hepatitis development (P < 0.001) as well as for HCC
      development (P < 0.01) with HCV-carrier group as reference. Both H139R and R139R,
      exon 4 genotypes, acted as a risk factor for HBV/HCV-chronic hepatitis infection
      and for HBV/HCV-HCC development (P ranges from < 0.05 to < 0.001) with HBV/HCV
      carriers as reference. 113His-139His and 113His-139Arg haplotypes shared a
      significant negative and positive association, respectively, with HBV hepatitis
      and HBV-HCC risk. 113Tyr-139Arg haplotype acted as a risk for HCV-HCC
      development. CONCLUSION: Polymorphic and haplotypic variant forms of mEPHX exon 3
      and 4 variably determine the susceptibility to develop HCC in HBV- and HCV
      carrier subjects.

PMID- 25755419
TI  - The Distribution of Genotype and Allelic Frequency of IL28B Gene Polymorphism in
      Andhra Pradesh, India.
AB  - BACKGROUND: The single nucleotide polymorphism (SNP) of IL28B gene on chromosome
      19, encoding for the interferon (IFN)-lambda-3 is strongly associated with
      treatment response to pegylated-IFN and ribavirin in patients infected with
      different genotypes of hepatitis C virus (HCV). Difference between ethnicity and
      treatment response rates suggesting a key role of host genetics. The IL28B
      polymorphism (rs12979860C/T) shows a marked differential distribution between
      racial groups. AIM: The present study is aimed to evaluate genotype and allelic
      frequency of IL28B gene polymorphism (rs12979860C/T) in Andhra Pradesh, India.
      METHODS: A total of 220 healthy controls were recruited for the study. The
      genotyping of SNP rs12979860C/T on IL28B gene was performed by polymerase chain
      reaction-direct sequencing method. RESULT: The frequency of CC genotype was found
      to be significantly (59.09%) higher compared to CT (34.09%) and TT (6.81%)
      genotypes, respectively. The frequency of major allele C is 0.762 whereas minor
      allele T is 0.238. CONCLUSION: The higher distribution of genotype 'CC' of SNP,
      rs12979860C/T of IL28B gene in study subjects is suggestive of better response of
      HCV patients to standard anti-HCV therapy.

PMID- 25755420
TI  - Brain perfusion single photon emission computed tomography abnormalities in
      patients with minimal hepatic encephalopathy.
AB  - BACKGROUND: Minimal hepatic encephalopathy (MHE) is the mildest form of hepatic
      encephalopathy (HE). Minimal hepatic encephalopathy patients do not demonstrate
      clinically overt symptoms of HE but present with abnormal neuropsychological
      and/or neurophysiological tests indicative of cerebral dysfunction. This study
      was performed in such patients to identify regions of abnormal cerebral perfusion
      and to correlate regional cerebral blood flow (rCBF) changes with psychometric
      hepatic encephalopathy score (PHES), Child-Turcotte-Pugh's score (CTP), and model
      for end-stage liver disease (MELD) score. We also compared abnormal patterns of
      rCBF in cirrhotic patients of alcoholic etiology with non-alcoholic etiology.
      METHODS: This prospective study was performed to evaluate rCBF in 50 cirrhotic
      patients and 13 controls using technetium-99m ethyl cysteinate dimer (Tc-99m ECD)
      brain single photon emission computed tomography. All the patients underwent a
      battery of psychometry tests, PHES. Minimal hepatic encephalopathy was diagnosed
      if PHES was <=-5. The rCBF changes were evaluated using region of interest (ROI)
      based semi-quantitative method of region/cerebellum and region/cortex ratios in
      16 regions of the brain. RESULTS: Cirrhotic patients with MHE showed impaired
      perfusion in the superior prefrontal cortex and increased perfusion in the
      thalamus, brain-stem, medial temporal cortex, and the hippocampus when compared
      with the controls. Cerebral perfusion in superior prefrontal cortex correlated
      negatively with MELD score (r=-0.323, P=0.022). We found significant positive
      correlation between PHES score and rCBF values in the left superior prefrontal
      cortex (r=0.385, P=0.006). Cirrhotic patients with alcohol etiology showed
      significantly decreased rCBF in right inferior prefrontal cortex, right superior
      prefrontal cortex, and the anterior cingulate cortex while increased rCBF was
      noted in the right medial temporal cortex and hippocampus. CONCLUSION: Our
      results suggest that alterations in cognition in cirrhotic patients with MHE may
      be associated with impaired abnormalities of rCBF.

PMID- 25755421
TI  - Non-alcoholic Fatty Liver Disease: East Versus West.
AB  - Non-alcoholic fatty liver disease (NAFLD) is an important cause of liver disease
      worldwide with prevalence ranging from 10% to 30% in various countries. It has
      become an important cause of unexplained rise in transaminases, cryptogenic
      cirrhosis, and cryptogenic hepatocellular carcinoma. Pathogenesis is related to
      obesity, insulin resistance, oxidative stress, lipotoxicity, and resultant
      inflammation in the liver progressing to fibrosis. Pharmacological treatment in
      patients with NAFLD is still evolving and the treatment of these patients rests
      upon lifestyle modification with diet and exercise being the cornerstones of
      therapy. While there are many similarities between patients with NAFLD from Asia
      and the West, there are certain features which make the patients with NAFLD from
      Asia stand apart. This review highlights the data on NAFLD from Asia comparing it
      with the data from the West. 

PMID- 25755422
TI  - Epidemiology and Natural History of Non-alcoholic Fatty Liver Disease.
AB  - Non-alcoholic fatty liver disease (NAFLD) is an important cause of liver disease
      burden across the world. By definition, although the histopathologic features of
      NAFLD are identical to that of alcoholic liver disease, its diagnosis requires
      absence of significant alcohol use and absence of other causes of chronic liver
      disease. We now know that NAFLD is not simply a disease of the Western world. It
      is manifested across the world, in varying rates, across gender, across varying
      ethnicities, and in its association with other host factors. In this review
      article, the definition of NAFLD, its spectrum, ranging from mild steatosis to
      hepatocellular injury and inflammation defined as non-alcoholic steatohepatitis
      (NASH) is discussed. Mild steatosis is generally a stable disease whereas NASH
      can be progressive. Based on current published literature, current incidence and
      prevalence of NAFLD and NASH are discussed. It is also accepted that these
      processes will continue to increase in prevalence with the rise of obesity, type
      II diabetes, and associated metabolic syndrome. Some of the risk factors have
      been well-established and are discussed. In addition, this review also presents
      emerging associations with other risk factors for NAFLD. Natural history of NAFLD
      is variable depending upon the histologic subtypes and other underlying
      comorbidities and is discussed in this review as well. 

PMID- 25755423
TI  - Non-invasive Diagnosis of Fibrosis in Non-alcoholic Fatty Liver Disease.
AB  - Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver
      disease in developed as well as in developing countries. Its prevalence continues
      to rise currently affecting approximately 20-30% of adults and 10% of children in
      the United States. Non-alcoholic fatty liver disease represents a wide spectrum
      of conditions ranging from fatty liver, which in general follows a benign non
      progressive clinical course, to non-alcoholic steatohepatitis (NASH), a more
      serious form of NAFLD that may progress to cirrhosis and end-stage liver disease.
      Liver biopsy remains the gold standard for evaluating the degree of hepatic
      necroinflammation and fibrosis; however, several non-invasive investigations,
      such as serum biomarkers, have been developed to establish the diagnosis and also
      to evaluate treatment response. There has been a substantial development of non
      invasive risk scores, biomarker panels, and radiological modalities to identify
      at risk patients with NAFLD without recourse to liver biopsy on a routine basis.
      Examples include combination of serum markers like NAFLD fibrosis score (NFS),
      BARD score, fibrometer, FIB4, and non-invasive tools like fibroscan which assess
      fibrosis in patients with NAFLD. Other markers of fibrosis that have been
      evaluated include high-sensitivity C-reactive protein, plasma pentraxin 3,
      interleukin-6, and cytokeratin-18. This review focuses on the methods currently
      available in daily clinical practice in hepatology and touches briefly on the
      potential future markers under investigation. 

PMID- 25755425
TI  - Hepatitis B virus genotyping: is the time ripe for routine clinical use?
AB  - Hepatitis B is one of the major causes of end-stage liver disease and liver
      cancer worldwide. A number of host and viral factors influence the disease course
      and outcomes. One such viral factor is hepatitis B virus (HBV) genotypes. There
      are eight major HBV genotypes described from various geographic regions of the
      world. Although direct sequencing appears to be the gold standard for HBV
      genotyping, it is expensive and laborintensive and therefore cannot be applied
      for routine clinical use. The newer molecular methods including serotyping have
      made genotyping easier and simple to apply to large number of samples rapidly.
      The data collected mainly over the last decade have suggested that HBV genotypes
      may have a bearing over the natural course of the disease and its response to
      therapy. This review summarizes the available literature and highlights how
      genotyping could be incorporated into routine clinical practice in order to
      improve delivery of care to HBV-infected individuals. 

PMID- 25755424
TI  - Management of Non-alcoholic Fatty Liver Disease and Steatohepatitis.
AB  - Non-alcoholic fatty liver disease (NAFLD) is the most common cause of abnormal
      liver enzymes and chronic liver disease in the US with expected rise in incidence
      paralleling the epidemic of obesity. A subset of patients with NAFLD have the
      progressive form of NAFLD that is termed non-alcoholic steatohepatitis (NASH),
      which is characterized by specific features on liver histology including
      hepatocellular ballooning degeneration, lobular inflammation, and zone-3
      steatosis with or without peri-sinusoidal fibrosis. Non-alcoholic steatohepatitis
      can progress to cirrhosis and result in liver-related death. Insulin resistance
      is commonly seen in patients with NASH and often co-exists with other features of
      the metabolic syndrome including hypertension, hyperlipidemia, and obesity.
      Although weight loss through lifestyle modifications including dietary changes
      and increased physical exercise remains the backbone of management of NASH, it
      has proved challenging for patients to achieve and maintain weight loss goals.
      Thus, it is often necessary to couple lifestyle changes with another
      pharmacologic treatment for NASH. Insulin sensitizers including the biguanides
      (metformin), thiazolidinediones (pioglitazone and rosiglitazone), and glucagon
      like peptide-1 receptor agonists (exenatide) are large groups of medications that
      have been studied for the treatment of NASH. Other agents with anti-inflammatory,
      anti-apoptotic, or anti-fibrotic properties which have been studied in NASH
      include vitamin E, pentoxifylline, betaine, and ursodeoxycholic acid. This review
      will provide a detailed summary on the clinical data behind the full spectrum of
      treatments that exist for NASH and suggest management recommendations. 

PMID- 25755427
TI  - Portal hypertension and ascites in extramedullary hematopoiesis.
AB  - Myeloproliferative diseases (MPD) are clonal stem cell disorders which mainly
      include polycythemia vera (PV), essential thrombocythemia (ET), and idiopathic
      myelofibrosis (IMF). They are characterized by leucocytosis, thrombocytosis,
      erythrocytosis, splenomegaly, and bone marrow hypercellularity. This might also
      result in extramedullary hematopoiesis. Abdominal manifestation has been
      recognized as a feature of these disorders. Splenomegaly and hepatomegaly are
      fairly common as opposed to ascites which is rare. The MPDs mainly affect the
      hepatic circulatory systems. The common hepatic manifestations are Budd-Chiari
      syndrome (BCS), portal vein thrombosis (PVT), and nodular regenerative
      hyperplasia. A few other features seen in MPDs are caused by extramedullary
      hematopoiesis, increased hepatic blood flow, and secondary hemosiderosis from
      multiple blood transfusions. Portal hypertension is found in up to 7% of
      patients. We report a case of portal hypertension with ascites in a patient with
      extramedullary hematopoiesis treated with transjugular intrahepatic portocaval
      shunt (TIPS). 

PMID- 25755426
TI  - Challenges and Outcome of Left-lobe Liver Transplants in Adult Living Donor Liver
      Transplants.
AB  - Adult-to-adult living donor liver transplant (LDLT) frequently depend on using
      the right-lobes of the donor for obtaining adequate graft-to-recipient weight
      ratio (GRWR) of over 0.8% in the recipient. However, left-lobes remain an
      important option in adults, since the morbidity in the donor is considerably less
      with left donor hepatectomy when compared with right side liver resection.
      Further benefits of left-lobes in LDLT include more predictable anatomy of the
      left hepatic duct and left portal vein, which are usually long and single
      resulting in easier anastomosis in the recipient. Likewise, left-lobe grafts are
      easier to implant with an excellent venous outflow through the combined orifice
      of left and middle hepatic vein, as opposed to the complex hepatic vein
      reconstruction required in right-lobe grafts. However, left hepatic artery is
      often multiple unlike the right hepatic artery. The holy grail of left-lobe
      transplants is avoidance of small for size syndrome (SFSS) in the recipients. The
      strategies for overcoming SFSS currently depend on circumventing portal
      hyperperfusion in the graft. Measurement of portal pressure and modulating it if
      high, by splenic artery ligation, splenectomy, or hemiportocaval shunts are
      proving successful in avoiding SFSS. The future aim in adult LDLT should be to
      use the left-lobe as much as possible for the benefit of the donor at the same
      time avoiding SFSS even at very low GRWR for the benefit of the recipient. 

PMID- 25755428
TI  - Fatal hepatitis C in a renal transplant recipient on immunosuppression.

PMID- 25755429
TI  - I. Beta-blockers: Finding the Right Timing and its Role in Cirrhosis.

PMID- 25755430
TI  - II. Ammonia in Acute Liver Failure: If the Level Does Not Decline, the Outcome of
      Acute Liver Failure Might.

PMID- 25755431
TI  - III. The Acute Liver Failure Early Dynamic Model: Dynamicity of Parameters may be
      the Key to Selecting Patients for Liver Transplantation.

PMID- 25755432
TI  - Multiple choice questions.

PMID- 25755434
TI  - Answers to multiple choice questions.

PMID- 25755433
TI  - Fatal hepatitis C in a renal transplant recipient on immunosuppression: fibrosing
      cholestatic hepatitis.

PMID- 25755435
TI  - Gut microbiota, inflammation and hepatic encephalopathy: a puzzle with a solution
      in sight.

PMID- 25755436
TI  - Hemochromatosis gene mutations: prevalence and effects on pegylated-interferon
      and ribavirin therapy response in chronic hepatitis C in sardinia.
AB  - BACKGROUND/AIMS: Considerable evidence suggests that iron could be a comorbid
      factor for liver injury in chronic hepatitis C (CHC). Elevated iron indices are
      frequently described in CHC and may impact negatively on the course of liver
      disease and on the response to interferon alfa therapy. The aim of this study was
      to evaluate the frequency of hemochromatosis gene mutations in Sardinian CHC
      patients, the association with iron overload and the impact on response to
      therapy. METHODS: Sixty-nine CHC patients were enrolled. Iron indices, hepatic
      and viral parameters were detected. C282Y, H63D and S65C mutations were
      identified through a PCR. Liver biopsy was performed for hepatic fibrosis
      evaluation. All patients were treated for 6 months (viral genotype 2/3) or 12
      months (viral genotype 1/4) with pegylated-interferon 180 mcg once weekly and
      ribavirin 1000-1200 mg/daily. Sustained virological response (SVR) was defined as
      undetectable HCV RNA 24 weeks after the end of treatment. RESULTS: HFE gene
      mutation was detected in 29 patients (42%). The presence of HFE mutations was
      significantly associated with elevated transferrin saturation (P < 0.01). Hepatic
      fibrosis was more advanced in HFE mutation carriers (chi (2), P = 0.04). Among
      mutation carriers 27.5% achieved responses at the end of treatment compared with
      60% of non-carriers (P = 0.005). Patients with HFE wildtype produced significant
      SVR compared with patients with HFE mutations (P = 0.03). CONCLUSIONS: The
      literature shows discordant results about the prevalence, hepatic distribution
      and possible therapeutic implications of iron overload in chronic hepatitis C.
      Our findings shows that HFE gene mutations could favor, synergically with CHC and
      other genetic or acquired factors, the development of liver damage and could
      influence the outcome of interferon treatment with higher rate of non-response.

PMID- 25755437
TI  - An Exploration of Depressive Symptoms in Hepatitis C Patients Taking Interferon
      alpha: Increase in Sickness Behaviors but not Negative Cognitions.
AB  - OBJECTIVE: The most investigated adverse event associated with interferon-alpha
      (IFN-alpha) treatment is depressed mood, with many studies finding a significant
      increase in depression scale scores from baseline to treatment. This paper is
      concerned with exploring discrete categories of depressive symptoms (somatic,
      behavioral, negative cognitions and depressed mood) in order to explore the
      behavioral syndrome associated with IFN-alpha. METHODS: Thirty-five Hepatitis C
      patients due to commence IFN-alpha treatment were assessed using the Structured
      Clinical Interview (SCID), and the 24-item Hamilton Depression Inventory (HAM-D)
      at 0 and 8 weeks. RESULTS: Somatic symptoms comprised the significant majority of
      scores across all weeks for patients taking IFN-alpha. Patients who developed a
      depression had significantly more somatic and mood symptoms at Week 8 than those
      patients who did not develop a depression. CONCLUSIONS: These exploratory results
      indicate that the increase in raw depression scores is due to an increase in
      somatic and mood symptoms, rather than negative cognitions. However, this
      increase does not correspond to a proportional increase in a particular subscale.
      These results also indicate that development of an IFN-alpha-induced depression
      is due to mood symptoms rather than negative cognitions.

PMID- 25755438
TI  - Multistix 10 SG Leukocyte Esterage Dipstick Testing in Rapid Bedside Diagnosis of
      Spontaneous Bacterial Peritonitis: A Prospective Study.
AB  - BACKGROUND AND AIMS: Spontaneous bacterial peritonitis (SBP) requires rapid
      diagnosis and the initiation of antibiotics. Diagnosis of SBP is usually based on
      cytobacteriological examination of ascitic fluid. These tests require good
      laboratory facilities and reporting time of few hours to 1-2 day. However, the 24
      h laboratory facilities not widely available in country like India. We evaluated
      the diagnostic utility of reagent strip (Multistix 10 SG((r))) for rapid
      diagnosis of SBP. MATERIAL AND METHODS: The study was prospectively carried out
      on patients of cirrhosis with ascites. Bedside leukocyte esterase reagent strip
      testing was performed on ascitic fluid. Cell count as determined by colorimetric
      scale of reagent strip was compared with counting chamber method. Sensitivity,
      specificity, positive predictive value, negative predictive value, and accuracy
      were calculated. RESULT: Out of 100 patients with cirrhotic ascites, [72 males:
      28 female; mean age 44.34 (SD 13.03) years] 18 patients were diagnosed to have
      SBP by counting chamber method as compared to 14 patients detected to have SBP by
      reagent strip test >=++ positive. The sensitivity, specificity, positive
      predictive value, negative predictive value and accuracy of reagent strip >=++
      positive were 77.77%, 95.12%, 77.77%, 95.12% and 92% respectively compared to
      counting chamber method. CONCLUSION: Reagent strip to diagnose SBP is very
      specific but less sensitive as compared to counting chamber method. This can be
      performed rapidly, easily and efficiently even in remote area of developing
      countries. This bedside test could be a useful tool for the diagnosis of SBP in
      country like India.

PMID- 25755439
TI  - Identification of Perforators in Patients with Duodenal Varices by Endoscopic
      Ultrasound-A Case Series [with video].
AB  - BACKGROUND/AIMS: Duodenal varices (DV) are ectopic varices which can cause
      massive gastrointestinal bleeding. The diagnosis of DV may be difficult;
      sometimes they can be hidden behind duodenal folds. The aim of the study was to
      evaluate DV by endoscopic ultrasound. METHODS: Endoscopic ultrasound was done in
      patients detected or suspected to be having DV. The para duodenal varices were
      identified and subsequently hemodynamic evaluation of DV was done. RESULTS:
      Endoscopic ultrasound identified perforators in seven cases of DV. CONCLUSION:
      The endoscopic ultrasound can help in detection of DV underlying thickened folds.
      It can also help in hemodynamic evaluation of DV.

PMID- 25755440
TI  - Surgery in a patient with liver disease.
AB  - Surgery is often needed in patients with concurrent liver disease. The multiple
      physiological roles of the liver places these patients at an increased risk of
      morbidity and mortality. Diseases necessitating surgery like gallstones and
      hernia are more common in patients with cirrhosis. Assessment of severity of
      liver dysfunction before surgery is important and the risk benefit of the
      procedure needs to be carefully assessed. The disease severity may vary from mild
      transaminase rise to decompensated cirrhosis. Surgery should be avoided if
      possible in the emergency setting, in the setting of acute and alcoholic
      hepatitis, in a patient of cirrhosis who is child class C or has a MELD score
      more than 15 or any patient with significant extrahepatic organ dysfunction. In
      this subset of patients, all possible means to manage these patients
      conservatively should be attempted. Modified Child-Pugh scores and model for end
      stage liver disease (MELD) scores can predict mortality after surgery fairly
      reliably including nonhepatic abdominal surgery. Pre-operative optimization would
      include control of ascites, correction of electrolyte imbalance, improving renal
      dysfunction, cardiorespiratory assessment, and correction of coagulation. Tests
      of global hemostasis like thromboelastography and thrombin generation time may be
      more predictive of the risk of bleeding compared with the conventional tests of
      coagulation in patients with cirrhosis. Correction of international normalized
      ratio with fresh frozen plasma does not necessarily mean reduction of bleeding
      risk and may increase the risk of volume overload and lung injury. International
      normalized ratio liver may better reflect the coagulation status. Recombinant
      factor VIIa in patients with cirrhosis needing surgery needs further study. Intra
      operatively, safe anesthetic agents like isoflurane and propofol with avoidance
      of hypotension are advised. In general, nonsteroidal anti-inflammatory drug
      (NSAIDs) and benzodiazepines should not be used. Intra-abdominal surgery in a
      patient with cirrhosis becomes more challenging in the presence of ascites,
      portal hypertension, and hepatomegaly. Uncontrolled hemorrhage due to
      coagulopathy and portal hypertension, sepsis, renal dysfunction, and worsening of
      liver failure contribute to the morbidity and mortality in these patients. Steps
      to reduce ascitic leaks and infections need to be taken. Any patient with
      cirrhosis undergoing major surgery should be referred to a specialist center with
      experience in managing liver disease. 

PMID- 25755441
TI  - An Update on Drug-induced Liver Injury.
AB  - Idiosyncratic drug-induced liver injury (DILI) is an important cause of morbidity
      and mortality following drugs taken in therapeutic doses. Hepatotoxicity is a
      leading cause of attrition in drug development, or withdrawal or restricted use
      after marketing. No age is exempt although adults and the elderly are at
      increased risk. DILI spans the entire spectrum ranging from asymptomatic
      elevation in transaminases to severe disease such as acute hepatitis leading to
      acute liver failure. The liver specific Roussel Uclaf Causality Assessment Method
      is the most validated and extensively used for determining the likelihood that an
      implicated drug caused DILI. Asymptomatic elevation in liver tests must be
      differentiated from adaptation. Drugs producing DILI have a signature pattern
      although no single pattern is characteristic. Antimicrobial and central nervous
      system agents including antiepileptic drugs are the leading causes of DILI
      worldwide. In the absence of a diagnostic test or a biomarker, the diagnosis
      rests on the evidence of absence of competing causes such as acute viral
      hepatitis, autoimmune hepatitis and others. Recent studies show that
      antituberculosis drugs given for active or latent disease are still a major cause
      of drug-induced liver injury in India and the West respectively. Presence of
      jaundice signifies a severe disease and entails a worse outcome. The pathogenesis
      is unclear and is due to a mix of host, drug metabolite and environmental
      factors. Research has evolved from incriminating candidate genes to genome wide
      analysis studies. Immediate cessation of the drug is key to prevent or minimize
      progressive damage. Treatment is largely supportive. N-acetylcysteine is the
      antidote for paracetamol toxicity. Carnitine has been tried in valproate injury
      whereas steroids and ursodeoxycholic acid may be used in DILI associated with
      hypersensitivity or cholestatic features respectively. This article provides an
      overview of the epidemiology, the patterns of hepatotoxicity, the pathogenesis
      and associated risk factors besides its clinical management. 

PMID- 25755442
TI  - A guide to the management of tuberculosis in patients with chronic liver disease.
AB  - Tuberculosis remains one of the 'Captains of the Men of Death' even today,
      particularly in the developing world. Its frequency is increased 14-fold in
      patients with chronic liver diseases (CLD) and liver cirrhosis, more so in those
      with decompensated disease, probably due to the cirrhosis-associated immune
      dysfunction syndrome, and case-fatality rates are high. The diagnosis of
      tuberculosis, particularly the interpretation of the Mantoux test, is also
      fraught with difficulties in CLD, especially after previous BCG vaccination.
      However, the greatest challenge in the patient with CLD or liver cirrhosis and
      tuberculosis is managing their therapy since the best first-line anti
      tuberculosis drugs are hepatotoxic and baseline liver function is often deranged.
      Frequency of hepatotoxicity is increased in those with liver cirrhosis, chronic
      hepatitis B and chronic hepatitis C, possibly related to increased viral loads
      and may be decreased following antiviral therapy. If hepatotoxicity develops in
      those with liver cirrhosis, particularly decompensated cirrhosis, the risk of
      severe liver failure is markedly increased. Currently, there are no established
      guidelines for anti-tuberculosis therapy (ATT) in CLD and liver cirrhosis
      although the need for such guidelines is self-evident. It is proposed that ATT
      should include no more than 2 hepatotoxic drugs (RIF and INH) in patients with
      CLD or liver cirrhosis and stable liver function [Child-Turcotte-Pugh (CTP) <=7],
      only a single hepatotoxic drug (RIF or INH) in those with advanced liver
      dysfunction (CTP 8-10) and no hepatotoxic drugs with very advanced liver
      dysfunction (CTP >=11). A standard protocol should be followed for monitoring ATT
      related hepatotoxicity and for stop rules and reintroduction rules in all these
      patients, on the lines proposed here. It is hoped that these proposals will
      introduce uniformity and result in streamlining the management of these difficult
      patients. 

PMID- 25755443
TI  - Perioperative monitoring in liver transplant patients.
AB  - Liver transplant (LT) is a major surgical undertaking involving major fluid
      shifts, hemodynamic instability and metabolic derangements in a patient with
      preexisting liver failure and multisystemic derangements. Monitoring and organ
      support initiated in the preoperative phase is continued intraoperatively and
      into the postoperative phase to ensure an optimal outcome. As cardiovascular
      events are the leading cause of non-graft related death among LT recipients,
      major emphasis is placed on cardiovascular monitoring. The other essential
      monitoring are the continuous assessment of coagulapathy, extent of metabolic
      derangements, dyselectrolytemis and intracranial pressure monitoring in patients
      with fulminant hepatic failure. The type and extent of monitoring differs with
      need according to preexisting child status of the patient and the extent of
      systemic derangements. It also varies among transplant centers and is mainly
      determined by individual or institutional practices. 

PMID- 25755444
TI  - Hepatology in India and INASL: A Ringside View.

PMID- 25755445
TI  - Sudden onset abdominal wall swellings in patient of liver cirrhosis.
AB  - Spontaneous hematomas in cirrhotic patients are uncommon. Severe coagulopathy in
      advanced hepatic disease is characterized by both coagulation factor deficiencies
      and accelerated fibrinolysis. Hyperfibrinolysis in cirrhosis is a result of
      excess fibrin breakdown leading to defective hemostasis. We present a case of
      spontaneous hematomas with an acute drop in hemoglobin level, in a patient with
      cirrhosis which was due to primary hyperfibrinolysis. 

PMID- 25755446
TI  - Massive infiltration of liver by metastatic adenocarcinoma: a rare cause of acute
      hepatic failure.
AB  - Acute liver cell failure can occur by diffuse infiltration of malignant cells in
      liver parenchyma. The malignant cells might be either primary hepatocellular
      carcinoma or metastatic liver disease. Mostly, CT abdomen with intravenous
      contrast fails to detect liver malignancy. We report a case of liver metastasis
      masquerading as fulminant hepatic failure. 

PMID- 25755447
TI  - An unusual complication of liver abscess.

PMID- 25755448
TI  - Coffee and liver - long way to go.

PMID- 25755449
TI  - Hepatobiliary quiz-3 (2012).

PMID- 25755450
TI  - Hepatobiliary quiz-3 (2012).

PMID- 25755451
TI  - Diagnosis of Minimal HE-And the Temptation of Easy Solutions.

PMID- 25755452
TI  - Inhibitory control test for the detection of minimal hepatic encephalopathy in
      patients with cirrhosis of liver.
AB  - BACKGROUND & AIMS: Minimal hepatic encephalopathy (MHE) has significant impact on
      future clinical outcomes, such as occurrence of overt HE (OHE) and survival in
      patients of cirrhosis. In the absence of a 'gold standard', psychometric hepatic
      encephalopathy score (PHES) is widely used for the diagnosis of MHE. This cross
      sectional and prospective study was carried out to determine the usefulness of
      inhibitory control test (ICT) for the diagnosis of MHE. METHODS: One hundred and
      two patients with cirrhosis and without a history of OHE were enrolled in to the
      study and were subjected to PHES and ICT. MHE was diagnosed when the PHES was <= 
      5. ICT was considered abnormal when the numbers of ICT lures were more than 14.
      RESULTS: Forty-one (40.2%) patients had MHE. There were 40 patients with normal
      PHES and ICT, 32 with abnormal PHES and ICT, 9 with abnormal PHES and normal ICT,
      and 21 with abnormal ICT and normal PHES score. ICT had 78% sensitivity and 65.6%
      specificity and an area-under-the-curve value of 0.735 (95% CI = 0.632-0.830) for
      the diagnosis of MHE. In patients with cirrhosis, ICT did not correlate with
      severity of liver disease as measured by CTP score (r = 0.044, P = 0.658) and
      MELD score (r = 0.176, P = 0.077). ICT did not predict survival as well as PHES;
      while 6 (11.3%) patients died among those who had altered ICT compared to 4
      (8.2%) patients who did not have altered ICT (P = 0.74), 8 (19.5%) patients died
      among those who had altered PHES compared to 2 (3.3%) patients who did not have
      altered PHES (P = 0.013). CONCLUSION: ICT is not as useful as PHES in diagnosing
      MHE in patients with cirrhosis of the liver. It does not correlate with disease
      severity and predict survival as well as PHES.

PMID- 25755453
TI  - Comparison of culture media for bile Acid transport studies in primary human
      hepatocytes.
AB  - BACKGROUND: Primary human hepatocytes are a useful in vitro model system to
      examine hepatic biochemical pathways, liver disorders and/or pharmacotherapies.
      This system can also be used for transport studies to investigate uptake and
      excretion of bile acids. Proper modeling of hepatic function requires careful
      attention to media components, and culture substrates and conditions. OBJECTIVES:
      To examine the effects of different culture media and conditions on bile acid
      transport in cultured human hepatocytes. METHODS AND RESULTS: Hepatocytes
      cultured in Williams' medium E showed an increase in both uptake and excretion of
      taurocholate compared to cells cultured in Dulbecco's Modified Eagle Medium
      (DMEM). Supplementation of DMEM with glutathione or ascorbic acid did not
      compensate for the lower transport. The difference can be explained by lower mRNA
      expression of the transporter proteins sodium taurocholate cotransporting
      polypeptide (NTCP) and bile salt export pump (BSEP; ABCB11) when cultured in
      DMEM. Hepatocytes cultured in DMEM also display fewer and smaller bile
      canaliculi. Following extended time in culture supplementation of Williams'
      medium E with dexamethasone increased the expression of NTCP and BSEP.
      CONCLUSION: Williams' medium E is superior to DMEM for transport studies in
      primary human hepatocytes. Supplementation with dexamethasone increase mRNA
      levels of NTCP and BSEP.

PMID- 25755454
TI  - Treprostinil Improves Hepatic Cytochrome P450 Activity during Rat Liver
      Transplantation.
AB  - BACKGROUND: Cytochrome P450 (CYP450) activity is an important indicator of liver
      graft function. CYP450 activity is altered by pro-inflammatory cytokines, which
      are associated with ischemia-reperfusion (I/R) injury during orthotopic liver
      transplantation (OLT). Treprostinil, an FDA-approved prostacyclin analog,
      ameliorated cold I/R injury during rat OLT. We hypothesized that treprostinil
      would improve CYP450 activity in liver graft during cold I/R injury post-OLT.
      METHODS: OLT was performed in syngeneic male Lewis rats with 18 h graft
      preservation in cold UW solution. Donor and recipients received treprostinil (100
      ng/kg/min) or matching placebo for 24 h before and up to 48 h post-OLT. Liver
      graft mRNA and protein expression of CYP450 isoforms were analyzed by qRT-PCR and
      Western blot analysis, respectively. The formation rates of 1-hydroxymidazolam
      and 6beta-hydroxytestosterone, 6-hydroxychlorzoxazone, 2alpha- and 16alpha
      hydroxytestosterone in liver graft microsomes served as markers for CYP3A,
      CYP2E1, and CYP2C11 activity, respectively, and were measured by LC-MS. RESULTS:
      Treprostinil significantly decreased serum ALT and AST levels at 6-48 h after
      OLT, compared to placebo. The expressions of TNFalpha and IFNgamma mRNA in the
      liver graft were significantly inhibited in the treprostinil-treated group at 1 h
      post-reperfusion. Treprostinil restored CYP2E1 protein expression to that of
      normal liver and significantly improved CYP3A activity to more than two-fold of
      placebo early post-OLT. CONCLUSIONS: Treprostinil significantly ameliorated
      hepatic injury, reduced expression of pro-inflammatory cytokines, and improved
      CYP450 activity in liver graft early post-OLT. These findings suggest that
      treprostinil has the potential to serve as a therapeutic option to protect liver
      graft function against I/R injury during clinical OLT.

PMID- 25755455
TI  - A Randomized Controlled Trial Comparing Efficacy of Pentoxifylline and
      Pioglitazone on Metabolic Factors and Liver Histology in Patients with Non
      alcoholic Steatohepatitis.
AB  - BACKGROUND AND AIMS: Non-alcoholic steatohepatitis (NASH) involves increased
      hepatic macrosteatosis due to increased insulin resistance and non-hepatic
      processes including oxidative stress, apoptosis, and increased pro-inflammatory
      cytokines. Present study compared the efficacy of pentoxifylline and pioglitazone
      therapy in improving the metabolic factors and liver histology in patients with
      NASH. METHODS: Sixty consecutive biopsy proven NASH patients aged 18-70 years
      with ALT > 1.2 times the upper limit of normal were randomized to receive either
      pentoxifylline 1200 mg/day in three divided doses orally every day or
      pioglitazone (30 mg/day) daily for 6 months. All the patients were also
      instructed to reduce their calorie intake by 500 kcal/day as well as to perform
      modest exercise (brisk walking) regularly at least 5 days per week. Before and
      after treatment, liver function tests, serum insulin, C-peptide levels, TNF
      alpha, adiponectin, leptin levels, HOMA-IR and hepatocyte injury and fibrosis
      scores on liver histology were assessed. RESULTS: Both pentoxifylline and
      pioglitazone were effective in improving transaminases, insulin resistance (HOMA
      IR) and adiponectin levels significantly. TNF-alpha levels improved with either
      of the drugs but did not achieve significant levels. Both the drugs improved the
      markers of acute liver injury. However, only steatosis improved significantly
      with either of the drugs. Patients treated with pioglitazone had significant
      improvement in lobular inflammation, portal inflammation and Brunts grade. Brunts
      grade improved significantly with pioglitazone as compared to pentoxifylline at
      the end of the therapy. CONCLUSIONS: Pioglitazone shows better improvement in
      both metabolic factors and liver histology in patients with NASH compared to
      pentoxifylline.

PMID- 25755456
TI  - Collateral pathways in portal hypertension.
AB  - Presence of portosystemic collateral veins (PSCV) is common in portal
      hypertension due to cirrhosis. Physiologically, normal portosystemic anastomoses
      exist which exhibit hepatofugal flow. With the development of portal
      hypertension, transmission of backpressure leads to increased flow in these
      patent normal portosystemic anastomoses. In extrahepatic portal vein obstruction
      collateral circulation develops in a hepatopetal direction and portoportal
      pathways are frequently found. The objective of this review is to illustrate the
      various PSCV and portoportal collateral vein pathways pertinent to portal
      hypertension in liver cirrhosis and EHPVO. 

PMID- 25755457
TI  - Molecular biology of the hepatitis B virus for clinicians.
AB  - Hepatitis B virus (HBV) infection is one of the major global health problems,
      especially in economically under-developed or developing countries. HBV infection
      can lead to a number of clinical outcomes including chronic infection, cirrhosis
      and liver cancer. It ranks among the top 10 causes of death, being responsible
      for around 1 million deaths every year. Despite the availability of a highly
      efficient vaccine and potent antiviral agents, HBV infection still remains a
      significant clinical problem, particularly in those high endemicity areas where
      vaccination of large populations has not been possible due to economic reasons.
      Although HBV is among the smallest viruses in terms of virion and genome size, it
      has numerous unique features that make it completely distinct from other DNA
      viruses. It has a partially double stranded DNA with highly complex genome
      organization, life cycle and natural history. Remarkably distinct from other DNA
      viruses, it uses an RNA intermediate called pregenomic RNA (pgRNA) and reverse
      transcriptase for its genome replication. Genome replication is accomplished by a
      complex mechanism of primer shifting facilitated by direct repeat sequences
      encoded in the genome. Further, the genome has evolved in such a manner that
      every single nucleotide of the genome is used for either coding viral proteins or
      used as regulatory regions or both. Moreover, it utilizes internal in-frame
      translation initiation codons, as well as different reading frames from the same
      RNA to generate different proteins with diverse functions. HBV also shows
      considerable genetic variability which has been related with clinical outcomes,
      replication potential, therapeutic response etc. This review aims at reviewing
      fundamental events of the viral life cycle including viral replication,
      transcription and translation, from the molecular standpoint, as well as,
      highlights the clinical relevance of genetic variability of HBV. 

PMID- 25755458
TI  - Chronic hepatitis B virus infection and pregnancy.
AB  - Planning of pregnancy and management of chronic hepatitis B virus during
      pregnancy includes recognition of maternal virological status, assessment of
      liver disease severity and minimization of risk for mother to infant transmission
      of infection. Decisions regarding the use of antivirals during pregnancy need to
      be individualized. Monitoring for infection and immunization in newborns is also
      important. For mothers on antiviral therapy, breastfeeding is not recommended. 

PMID- 25755460
TI  - Portosystemic myelopathy: a rare neurological presentation of portosystemic
      shunts.
AB  - Portosystemic myelopathy is an unusual complication in patients with chronic
      liver disease with hepatic encephalopathy and portosystemic shunts. Here we
      present a case of 35-year-old male patient who presented to us with difficulty in
      walking and progressive stiffness in both lower limbs for two months. He had
      undergone splenectomy with distal splenorenal shunt 20 years back. On physical
      examination, he had spasticity in both lower limbs of grade 3, with minimal
      pyramidal weakness in lower limbs, brisk knee and ankle jerks. The plantar
      response was extensor. Upper limb examination was normal. On investigations, he
      had hypoalbuminemia, hyperbilirubinemia, increased plasma ammonia levels.
      Contrast enhanced CT scan abdomen revealed dilated splenorenal shunt and MRI
      spine showed no spinal cord compression. Electromyoneurogram was also normal.
      Spastic paraparesis due to portosystemic shunts was diagnosed. Liver
      transplantation can reverse the myelopathy only in earlier stages, hence early
      and accurate diagnosis is important. 

PMID- 25755461
TI  - Will vitamin d supplementation have a role in the treatment of patients with
      chronic hepatitis C?

PMID- 25755459
TI  - Liver transplant-psychiatric and psychosocial aspects.
AB  - Liver transplantation is a life saving surgical procedure that is associated with
      improved longevity and enhanced quality of life. The number of successful liver
      transplants is growing worldwide. The procedure requires a dedicated and trained
      team of experts. A psychiatrist plays an important role in such a team.
      Psychiatric and psychosocial assessment is considered imperative to evaluate the
      candidate's suitability as a transplant recipient. Many psychiatric disorders may
      lead to the need for liver transplant, and if kept unchecked can adversely affect
      outcomes. Psychiatric problems arising in the post-transplant period may also
      require intervention of the psychiatrist. The donor too needs to be evaluated
      adequately to assess for psychological fitness for the procedure. This article
      provides broad overview of the various psychiatric and psychosocial issues
      pertaining to liver transplantation. 

PMID- 25755462
TI  - Multiple choice questions.

PMID- 25755464
TI  - The third year: thrice as good!

PMID- 25755463
TI  - Answers to multiple choice questions.

PMID- 25755465
TI  - Quo vadis: from oxidative stress to gamma-glutamyltransferase upregulation to
      mortality.

PMID- 25755467
TI  - Gastric Varices in Cirrhosis versus Extrahepatic Portal Venous Obstruction and
      Response to Endoscopic N-Butyl-2-cyanoacrylate Injection.
AB  - BACKGROUND: Gastric varices are found in patients with portal hypertension.
      Incidence of bleeding from gastric varices is relatively low, but tends to be
      more severe, and is associated with higher mortality than esophageal variceal
      bleeding. AIMS AND OBJECTIVES: To compare the prevalence and types of gastric
      varices in cirrhosis versus extrahepatic portal venous obstruction (EHPVO) and
      the results of endoscopic N-butyl-2-cyanoacrylate (NBC, glue) injection. METHODS:
      Eighty six patients presenting with bleeding from gastric varices between August
      2010 and August 2011 were retrospectively analyzed. RESULTS: Of 86 patients, 65%
      (n = 56) were cirrhotics and 35% (n = 30) had EHPVO. Distribution of types of
      gastric varices showed GOV1 in 14% (n = 8) of cirrhotics vs. 7% (n = 2) of EHPVO,
      GOV2 in 80% (n = 45) of cirrhotics vs. 53% (n = 16) of EHPVO, IGV1 in 40% (n =
      12) of patients with EHPVO vs. 4% (n = 2) cirrhotics. The patients were treated
      with NBC injections. The mean volume of glue injected was 3.7 +/- 2.58 ml over a
      median of 1 session (range: 1-8). The total volume of glue required was lower in
      cirrhotics (3.2 +/- 2 ml vs. 4.7 +/- 3.1 ml, p < 0.05) than in EHPVO patients.
      Twenty (36%) of cirrhotics required >1 sessions of glue injection as compared to
      17 (57%) of EHPVO patients. Over mean follow up of 12 months, rebleeding (9% vs.
      10%) and mortality (11% vs. 3%) were similar in patients with cirrhosis and
      EHPVO. CONCLUSIONS: In patients with bleeding from gastric varices, GOV2 is more
      common in cirrhotics and IGV1 in patients with EHPVO. Patients with EHPVO
      required higher total volume of glue and more glue sessions for gastric varix
      obturation.

PMID- 25755468
TI  - Profile of hepatitis B virus, hepatitis C virus, hepatitis d virus and human
      immunodeficiency virus infections in hemodialysis patients of a tertiary care
      hospital in uttarakhand.
AB  - BACKGROUND AND AIM: Viral hepatitis and human immunodeficiency virus (HIV)
      infection are important causes of morbidity and mortality in hemodialysis (HD)
      patients. The present study was performed to assess the prevalence of hepatitis B
      virus (HBV), hepatitis C virus (HCV), hepatitis D virus (HDV) and HIV infections
      in hemodialysis patients of a tertiary care hospital in Uttarakhand. METHODS: All
      patients undergoing maintenance HD at our center were screened for hepatitis B
      surface antigen (HBsAg), antibody to HCV (anti-HCV), antibody to HDV (anti-HDV)
      and HIV antibody by ELISA. Detailed history regarding age, sex, duration of
      dialysis, blood transfusions, number of dialysis centers, dialyzer reuse and
      laboratory data was recorded. RESULTS: A total of 118 patients (79 males and 39
      females) were followed for 18 months with screening for the presence of HBV, HCV
      and HIV infections. At baseline, 12 (10.2%) patients were positive for HBsAg, 19
      (16.1%) for anti-HCV and 2 (1.7%) for HIV antibody. Over 18 months, one
      additional patient became HBsAg positive and an additional 17 became anti-HCV
      positive to give a total of 36 HCV-positive patients. Dual HBV and HCV infection
      was seen in 5 (4.2%) and anti-HDV antibodies were found in 1 (0.9%) patient.
      History of blood transfusions, duration of HD, dialyzer reuse and dialysis at
      multiple centers were found to be important risk factors for anti-HCV positivity.
      CONCLUSIONS: Implementation and adherence to universal work precautions by
      dialysis staff is imperative to prevent transmission of these infections.

PMID- 25755466
TI  - Patients with Nonalcoholic Fatty Liver Disease (NAFLD) have Higher Oxidative
      Stress in Comparison to Chronic Viral Hepatitis.
AB  - INTRODUCTION: Oxidative stress and cytokines play an important role in the
      pathogenesis of nonalcoholic fatty liver disease (NAFLD). We compared the
      presence of oxidative stress and cytokines in 25 patients with NAFLD with 25 age,
      sex and BMI-matched patients with chronic viral hepatitis (CVH) and 25 healthy
      volunteers (HV). METHODOLOGY: Oxidative stress was studied biochemically by
      markers of lipid peroxidation and biochemical assessment of anti-oxidant status
      and various cytokines were studied by ELISA. RESULTS: Patients with NAFLD had
      significantly higher levels of malondialdehyde (MDA) (p = 0.000) and conjugated
      dienes (CD) (p = 0.000) in comparison to HVs. Patients with NAFLD also had
      significantly higher MDA levels (p = 0.000) in comparison to CVH patients.
      Patients with NAFLD had significantly lower GSH levels (p = 0.004) in comparison
      to HVs. Patients with NAFLD had higher GPx activity (p = 0.028) in comparison to
      HVs. Catalase activity was significantly decreased in both NAFLD (p = 0.001) and
      CVH patients (p = 0.000) in comparison to HVs. Patients with NAFLD had
      significantly higher SOD activity (p = 0.000) in comparison to CVH patients.
      There was no difference in serum levels of IL-1beta and TNF-alpha amongst three
      groups. Patients with CVH were found to have higher IL-8 serum levels (p = 0.039)
      in comparison to HVs. CVH patients also had higher TGF-beta levels (p = 0.002) in
      comparison to both NAFLD patients and HVs. CONCLUSION: Differences in the markers
      of oxidative stress and anti-oxidant status between NAFLD, CVH and healthy
      volunteers suggest presence of higher oxidative stress in patients with NAFLD.

PMID- 25755469
TI  - Protective effect of black tea infusion on aflatoxin-induced hepatotoxicity in
      mice.
AB  - BACKGROUND: Aflatoxins are a group of mycotoxins produced by Aspergillus flavus
      and Aspergillus parasiticus and are potent inducers of hepatotoxicity. OBJECTIVE:
      The present study was carried out to investigate the effect of black tea infusion
      on aflatoxin-induced hepatotoxicity in male mice. METHODS: A 2% black tea
      infusion in drinking water was prepared and orally administered along with
      aflatoxin (750 and 1500 MUg/kg body weight) for 30 days. Morphological
      investigation, body weight and organ weight calculations and histopathological
      analysis were carried out. Serum hepatic marker enzymes namely alanine
      aminotransferase and aspartate aminotransferase were estimated. RESULTS: The
      results clearly indicated that aflatoxin treatment for 30 days caused significant
      dose-dependent reduction in body weight and increase in liver weight. The
      activities of ALT and AST were found to be elevated while protein content was
      found to be decreased in aflatoxin-treated mice as compared to vehicle control.
      Histopathological analysis showed hepatocellular necrosis and cytoplasmic
      vacuolization along with fatty infiltration in toxin-treated animals. Results
      revealed significant (p < 0.05) restoration of aflatoxin-induced damages in body
      weight, organ weight, serum chemistry and histopathological features in aflatoxin
      plus black tea infusion administered mice in a dose dependant manner. CONCLUSION:
      It is concluded from the present study that supplementation of black tea infusion
      can be beneficial in positively modulating aflatoxin-induced alterations in
      liver.

PMID- 25755472
TI  - Living Donor Liver Transplant is a Transparent Activity in India.
AB  - Living donor liver transplant (LDLT) has progressed rapidly in India with at
      least two major centers performing over 200 transplants annually. There have been
      concerns regarding donor safety as donor deaths have been reported worldwide. In
      India, there is a possible underreporting of donor complications and mortality
      leading to the allegation that LDLT is a clandestine activity. Deceased donor
      liver transplantation activity may be less transparent as there are no national
      guidelines for retrieval and allocation of organs. LDLT is for a named person and
      as the activity can only be conducted in major hospitals with involvement of over
      100 medical personnel in each operation, it cannot be a clandestine operation.
      Government regulations require licensing of hospitals following inspection by
      senior doctors and reporting of transplant activity periodically. About 2500
      living donor liver transplants have been conducted in India and there have been 7
      donor deaths reported in India. Rather than not being transparent, donor
      morbidity and mortality has received excessive media attention. Most liver
      transplant activity in India is well organized with clearance from hepatologists
      and anesthetists. Unrelated donation needs to be cleared from a State appointed
      Authorization Committee. Foreigners cannot be transplanted without State
      clearance and approval of the concerned embassy. The donor risk is discussed and
      the success of the recipient operation is also explained to all patients. The
      ever-increasing popularity of the operation in spite of the high cost and the
      requirement for donation from a family member suggests that many patients are
      living healthy life after transplantation. Overall LDLT is a transparent activity
      in India. 

PMID- 25755470
TI  - Hepatotoxicity Related to Anti-tuberculosis Drugs: Mechanisms and Management.
AB  - Development of idiosyncratic hepatotoxicity is an intricate process involving
      both concurrent as well as sequential events determining the direction of the
      pathways, degree of liver injury and its outcome. Decades of clinical observation
      have identified a number of drug and host related factors that are associated
      with an increased risk of antituberculous drug-induced hepatotoxicity, although
      majority of the studies are retrospective with varied case definitions and sample
      sizes. Investigations on genetic susceptibility to hepatotoxicity have so far
      focused on formation and accumulation reactive metabolite as well as factors that
      contribute to cellular antioxidant defense mechanisms and the environment which
      can modulate the threshold for hepatocyte death secondary to oxidative stress.
      Recent advances in pharmacogenetics have promised the development of refined
      algorithms including drug, host and environmental risk factors that allow better
      tailoring of medications based on accurate estimates of risk-benefit ratio.
      Future investigations exploring the pathogenesis of hepatotoxicity should be
      performed using human tissue and samples whenever possible, so that the novel
      findings can be translated readily into clinical applications. 

PMID- 25755473
TI  - Living Donor Liver Transplant is not a Transparent Activity in India.
AB  - Living donor liver transplant has gained rapid popularity in India as a life
      saving procedure for end stage liver disease. The undoubted benefit for the
      recipient is clouded by a few unfavorable outcomes in donors which have led to
      allegations of lack of transparency. These factors are easily remediable with an
      attitude of self audit and self disclosure by transplant centers, enabling a
      truly informed consenting procedure. 

PMID- 25755471
TI  - Model for End-stage Liver Disease.
AB  - Model for end-stage liver disease (MELD) score, initially developed to predict
      survival following transjugular intrahepatic portosystemic shunt was subsequently
      found to be accurate predictor of mortality amongst patents with end-stage liver
      disease. Since 2002, MELD score using 3 objective variables (serum bilirubin,
      serum creatinine, and institutional normalized ratio) has been used worldwide for
      listing and transplanting patients with end-stage liver disease allowing
      transplanting sicker patients first irrespective of the wait time on the list.
      MELD score has also been shown to be accurate predictor of survival amongst
      patients with alcoholic hepatitis, following variceal hemorrhage, infections in
      cirrhosis, after surgery in patients with cirrhosis including liver resection,
      trauma, and hepatorenal syndrome (HRS). Although, MELD score is closest to the
      ideal score, there are some limitations including its inaccuracy in predicting
      survival in 15-20% cases. Over the last decade, many efforts have been made to
      further improve and refine MELD score. Until, a better score is developed, liver
      allocation would continue based on the currently used MELD score. 

PMID- 25755474
TI  - Successful Treatment of Rapid Onset, Symptomatic de novo Non-alcoholic
      Steatohepatitis Following Liver Transplantation: A Case Report.
AB  - A 45 year old female with a body mass index (BMI) of 24 underwent successful
      liver transplantation (LT) for alcoholic cirrhosis using a donor liver from an
      obese woman with microvesicular steatosis (80%) and minimal macrovesicular
      steatosis (5-10%) on liver biopsy. Ascites and hepatosplenomegaly developed soon
      after LT with progressive increase of serum alkaline phosphatase to 1340 IU/L
      while aspartate aminotransferase (AST), and alanine transaminase (ALT), and total
      bilirubin remained normal. Imaging showed marked hepatomegaly, extensive fatty
      infiltration of the liver, and compression of the hepatic veins with narrowing of
      the intrahepatic inferior vena cava (IVC). Liver biopsy on post-operative day 39
      revealed 90-100% macrovesicular steatosis, steatohepatitis, and portal fibrosis.
      A hepatic venogram showed a 10 cm segment of intrahepatic IVC stenosis that was
      stented, improving portal venous pressure measurements. However, portal
      hypertension requiring diuretic therapy and multiple paracenteses remained. By 3
      months after LT, her liver had grown to 22 cm, transaminases increased 2-4 times
      the upper limit of normal with a 2:1 AST to ALT ratio. Liver biopsy at post-LT
      day 82 showed no change in steatosis and steatohepatitis despite corticosteroid
      withdrawal and interval periportal and perisinusoidal fibrosis. 12 weeks after
      LT, the patient was found to have low apolipoprotein B (65 mg/dL), high-density
      lipoprotein (HDL) (<10 mg/dL), low-density lipoproteins (LDL) (9 mg/dL), and
      total cholesterol (<50 mg/dL) levels. Therapy was started for NASH with high dose
      (800 IU daily) vitamin E and pioglitazone 15 mg daily, and she received topical
      vegetable oil and oral essential fatty acid supplements. Liver enzymes normalized
      after 3 months and her lipid profile improved markedly (HDL 27 mg/dL, total
      cholesterol 128 mg/dL), with progressive decrease in liver size and resolution of
      ascites after 5 months of therapy. At 2 years post-LT, the liver enzymes remain
      normal and lipids have normalized. 

PMID- 25755475
TI  - A patient with unexplained ascites.

PMID- 25755476
TI  - Interferon-free regimens for chronic hepatitis C-a step forward.

PMID- 25755477
TI  - Hepatobiliary quiz-5 (2013).

PMID- 25755479
TI  - High Incidence of Telaprevir-associated Severe Rash Leading to Discontinuation.

PMID- 25755478
TI  - Hepatobiliary quiz-5 (2013).

PMID- 25755480
TI  - Scalloping of liver in a patient with ascites: pseudomyxoma peritonei.

PMID- 25755482
TI  - Elastography and Contrast-enhanced Ultrasonography in the Early Detection of
      Hepatocellular Carcinoma in an Experimental Model of Nonalcoholic
      Steatohepatitis.
AB  - BACKGROUND/OBJECTIVE: The early detection of focal hepatic lesions using
      ultrasound scanning is challenging, and this challenge becomes even greater in
      the presence of diffuse parenchymal disease. This study aimed to evaluate the
      diagnostic performance of elastography and contrast-enhanced ultrasonography
      (CEUS) in the early detection of hepatocellular lesions in an experimental rat
      model of nonalcoholic steatohepatitis (NASH). METHODS: B-mode and Doppler
      ultrasonography was performed weekly in 30 rats divided into a NASH group (n =
      20) and a group without liver disease (n = 10). The animals underwent
      elastography and CEUS and were then euthanized. Liver nodules were assessed by
      histopathology. RESULTS: Doppler mapping results of lesions with vascularization
      were considered indicative of malignancy, with a sensitivity of 29% before and
      71% after contrast injection. The specificity was 71% before and 96% after CEUS.
      Elastograms of positive lesions showed areas of high stiffness, which were
      indicative of malignancy. This malignancy was confirmed by the histologic
      evaluation, with a sensitivity of 90% and a specificity of 60%. After CEUS
      analysis, 4 nodules were identified that were not observed on B-mode
      ultrasonography. Early wash-in was significantly associated with malignancy
      (sensitivity of 88% and specificity of 67%). CONCLUSIONS: Both techniques allow
      for the correct diagnosis of well-differentiated to moderately differentiated
      hepatocellular carcinomas with good accuracy in an experimental rat model of
      NASH.

PMID- 25755481
TI  - Reduced Expression of DNA Damage Repair Genes High Mobility Group Box1 and
      Poly(ADP-ribose) Polymerase1 in Inactive Carriers of Hepatitis B Virus Infection
      A Possible Stage of Viral Integration.
AB  - BACKGROUND: High mobility group box1 (HMGB1) and poly(ADP-ribose) polymerase1
      (PARP1) proteins repair cellular DNA damage. Reduced expression of the
      corresponding genes can lead to an impaired DNA damage repair mechanism.
      Intracellular replication of hepatitis B virus (HBV) in such conditions can favor
      the integration of viral DNA into host genome leading to the development of
      hepatocellular carcinoma (HCC). OBJECTIVE: This study was performed to assess the
      expression of HMGB1 and PARP1 mRNAs in conjunction with the estimation of HBV
      replication intermediate pregenomic RNA (PgRNA) in various phases of HBV
      infection. MATERIALS: Eighty eight patients and 26 voluntary blood donors as
      controls were included in the study. Patients were grouped in to acute (AHB; n =
      15), inactive carriers (IC; n = 36), cirrhosis (Cirr; n = 25) and hepatocellular
      carcinoma (HCC; n = 12). Serum HBV DNA was quantified by real time polymerase
      chain reaction (PCR) assay. Expression of HMGB1, PARP1 and PgRNA were evaluated
      using peripheral blood mononuclear cells (PBMCs) derived RNA by reverse
      transcription PCR (RT-PCR) and densitometry. RESULTS: Significant reduction of
      HMGB1 and PARP1 gene expressions (P < 0.05) were observed in patients than
      controls with more explicit decline of PARP1 (P = 0.0002). Both genes were
      significantly downregulated (P < 0.001) in ICs than controls. In ICs, HMGB1 was
      significantly lowered than cirrhosis (P = 0.002) and HCC (P = 0.0006) while PARP1
      declined significantly (P = 0.04) than HCC. Level of PgRNA was comparable in all
      the disease categories. CONCLUSION: In conclusion, our findings indicate impaired
      DNA damage repair mechanisms in HBV infected cells of ICs. This, along with low
      viral load but higher level of PgRNA in this group is suggestive of the diversion
      of HBV replication pathway that might facilitate viral DNA integration in to host
      genome. Intrusion of HBV PgRNA reverse transcription in early stage of infection
      might appear advantageous to thwart the development of HCC.

PMID- 25755483
TI  - Hepatic artery Doppler indices in children with extra hepatic portal vein
      obstruction.
AB  - Doppler measurement provides information on the hemodynamics in the hepatic
      artery and the portal venous system. AIM: To study the hepatic artery
      hemodynamics in children with extra hepatic portal vein obstruction. MATERIALS
      AND METHODS: Hepatic artery indices were studied using Doppler indices in 15
      children (<12 years) with extra hepatic portal hypertension (EHPVO) and
      obliterated esophageal varices. The hepatic artery resistive index, the arterial
      acceleration time and the acceleration index were used to determine the flow
      pattern within the hepatic artery. Controls were 15 healthy age-sex matched
      children, belonging to the same socioeconomic strata in absence of liver disease.
      RESULTS: The mean age of the children was 8.43 +/- 3.2 years and male female
      ratio was 4:1. All the children had obliterated esophageal varices. The hepatic
      artery resistive index in the children with EHPVO was normal and similar to
      controls. The hepatic arterial early systolic acceleration index was
      significantly higher in cases compared to controls (436 +/- 290 vs 214 +/- 100; P
      value <0.004). The hepatic arterial acceleration time though low in the cases (86
      +/- 35 cm/s) was not statistically different from the controls (128 +/- 14 cm/s).
      CONCLUSION: There was a significant increase in hepatic arterial early systolic
      acceleration in children with chronic EHPVO. The latter may be responsible for an
      increase in hepatic arterial in flow velocity in a slow flow system despite a
      normal resistive index.

PMID- 25755484
TI  - The future liver of the Asia pacific: fatter and firmer from more fructose and
      fortune?
AB  - The Asia Pacific region is the most diverse and the most populous region in the
      world. Recent socioeconomic changes have resulted in an emerging epidemic of non
      communicable diseases such as type 2 diabetes and nonalcoholic fatty liver
      disease. The prevalence of nonalcoholic fatty liver disease in Asian Pacific
      countries now approximates that seen in Western countries. This increase is
      fueled by rising obesity, partly due to adoption of Western style diets and
      exposure to compounds such as high fructose corn syrup that are not included in
      traditional diets. Furthermore, South Asian populations may be more genetically
      susceptible via the inheritance of polymorphisms in apolipoprotein 3 that
      increase insulin resistance and nonalcoholic fatty liver disease. Importantly,
      there remains a substantial lack of data on the incidence and natural history of
      nonalcoholic steatohepatitis and subsequent complications such as hepatocellular
      carcinoma in Asian Pacific populations. This information gap prevents estimation
      of current and future disease burden and impedes efforts to lobby health
      policymakers to improve public health measures, as given the size of Asian
      Pacific populations, prevention rather than treatment of non-communicable
      diseases remains key. This review article addresses these issues and highlights
      research priorities for nonalcoholic fatty liver disease within the Asia Pacific
      region. 

PMID- 25755485
TI  - Hepatitis e: molecular virology and pathogenesis.
AB  - Hepatitis E virus is a single, positive-sense, capped and poly A tailed RNA virus
      classified under the family Hepeviridae. Enteric transmission, acute self
      limiting hepatitis, frequent epidemic and sporadic occurrence, high mortality in
      affected pregnants are hallmarks of hepatitis E infection. Lack of an efficient
      culture system and resulting reductionist approaches for the study of replication
      and pathogenesis of HEV made it to be a less understood agent. Early studies on
      animal models, sub-genomic expression of open reading frames (ORF) and infectious
      cDNA clones have helped in elucidating the genome organization, important stages
      in HEV replication and pathogenesis. The genome contains three ORF's and three
      untranslated regions (UTR). The 5' distal ORF, ORF1 is translated by host
      ribosomes in a cap dependent manner to form the non-structural polyprotein
      including the viral replicase. HEV replicates via a negative-sense RNA
      intermediate which helps in the formation of the positive-sense genomic RNA and a
      single bi-cistronic sub-genomic RNA. The 3' distal ORF's including the major
      structural protein pORF2 and the multifunctional host interacting protein pORF3
      are translated from the sub-genomic RNA. Pathogenesis in HEV infections is not
      well articulated, and remains a concern due to the many aspects like host
      dependent and genotype specific variations. Animal HEV, zoonosis, chronicity in
      immunosuppressed patients, and rapid decompensation in affected chronic liver
      diseased patients warrants detailed investigation of the underlying pathogenesis.
      Recent advances about structure, entry, egress and functional characterization of
      ORF1 domains has furthered our understanding about HEV. This article is an effort
      to review our present understanding about molecular biology and pathogenesis of
      HEV. 

PMID- 25755486
TI  - Hepatitis e: epidemiology and natural history.
AB  - Hepatitis E is a disease caused by infection with hepatitis E virus (HEV). The
      virus has four genotypes, named 1 to 4, with one shared serotype. Genotypes 1 and
      2 infect only humans, whereas genotypes 3 and 4 primarily infect several
      mammalian animals, with occasional transmission to humans. Evidence of infection
      with HEV has been found in most parts of the world, with two distinct
      epidemiological patterns. In areas with high disease endemicity, primarily
      developing countries in Asia and Africa, the disease occurs as outbreaks and as
      sporadic cases of acute hepatitis, and is caused exclusively by infection with
      genotypes 1 or 2 HEV, which is acquired through fecal-oral route, usually through
      contamination of water supplies. The disease in these areas occurs most commonly
      in young adults, and is particularly severe in pregnant women and persons with
      pre-existing chronic liver disease; chronic infection has not been reported. In
      areas with lower endemicity, which are mainly developed areas with robust water
      supply and sanitation systems, occasional sporadic cases of locally-acquired
      genotype 3 or 4 HEV infection are observed. The affected persons are often
      elderly and have other coexisting illnesses. The reservoir of infection in these
      areas is believed to be in animals, such as pigs, wild boar and deer, with
      zoonotic transmission to humans, possibly through consumption of undercooked
      meat. Also, in these areas, persistent HEV infection has been well documented
      among immunosuppressed persons such as organ transplant recipients, and is
      believed to lead to chronic liver injury, including liver cirrhosis. Further work
      is needed to better understand the biological basis underlying these widely
      differing epidemiological patterns. 

PMID- 25755487
TI  - Chronic hepatitis e virus infection and treatment.
AB  - It is now well accepted that hepatitis E virus (HEV) infection can induce chronic
      hepatitis and cirrhosis in immunosuppressed patients. Chronic genotype-3 HEV
      infections were first reported in patients with a solid-organ transplant.
      Thereafter, cases of chronic HEV infection have been reported in patients with
      hematological disease and in those who are human immunodeficiency virus (HIV)
      positive. HEV-associated extra-hepatic manifestations, including neurological
      symptoms, kidney injuries, and hematological disorders, have been also reported.
      In transplant patients, reducing the dosage of immunosuppressive drugs allows the
      virus to be cleared in some patients. In the remaining patients, as well as
      hematological patients and patients who are HIV-positive, anti-viral therapies,
      such as pegylated interferon and ribavirin, have been found to be efficient in
      eradicating HEV infection. This review summarizes our current knowledge of
      chronic HEV infection, its treatment, and the extra-hepatic manifestations
      induced by HEV. 

PMID- 25755488
TI  - Gut-liver axis: role of inflammasomes.
AB  - Inflammasomes are large multiprotein complexes that have the ability to sense
      intracellular danger signals through special NOD-like receptors or NLRs. They
      include NLRP3, NLRC4, AIM2 and NLRP6. They are involved in recognizing diverse
      microbial (bacteria, viruses, fungi and parasites), stress and damage signals,
      which result in direct activation of caspase-1, leading to secretion of potent
      pro-inflammatory cytokines and pyroptosis. NLRP3 is the most studied
      antimicrobial immune response inflammasome. Recent studies reveal expression of
      inflammasomes in innate immune response cells including monocytes, macrophages,
      neutrophils, and dendritic cells. Inflammasome deficiency has been linked to
      alterations in the gastrointestinal microflora. Alterations in the microbiome
      population and/or changes in gut permeability promote microbial translocation
      into the portal circulation and thus directly to the liver. Gut derived
      lipopolysaccharides (LPS) play a significant role in several liver diseases.
      Recent advancements in the sequencing technologies along with improved methods in
      metagenomics and bioinformatics have provided effective tools for investigating
      the 10(14) microorganisms of the human microbiome that inhabit the human gut. In
      this review, we examine the significance of inflammasomes in relation to the gut
      microflora and liver. This review also highlights the emerging functions of human
      microbiota in health and liver diseases. 

PMID- 25755490
TI  - Polymorphisms in ABCB11 and ATP8B1 Associated with Development of Severe
      Intrahepatic Cholestasis in Hodgkin's Lymphoma.
AB  - We report a young man presenting with jaundice and severe debilitating
      intrahepatic cholestasis 7 months before the diagnosis of Hodgkin's lymphoma.
      Serum gamma-glutamyl transferase (GGT) activity was not raised. Liver biopsy
      demonstrated deficiency of canalicular GGT and bile salt export pump expression,
      which suggested "benign" recurrent intrahepatic cholestasis. Direct sequencing of
      genomic DNA was therefore undertaken to look for mutations in ATP8B1 and ABCB11.
      Cholestasis and pruritus are well recognized presenting features of Hodgkin's
      lymphoma. However, striking in this case is that the intrahepatic cholestasis
      presented and resolved 7 months before the diagnosis. Furthermore, 4
      polymorphisms were identified in ATP8B1 in this patient-c.696T > C (rs319438),
      c.811A > C (rs319438), c.2855G > A (rs1296811) and c.3454G > A (rs222581)-and two
      polymorphisms in ABCB11-c.1331T > C (rs2287622) and c.3084A > G (rs497692); 2 of
      which have been associated with intrahepatic cholestasis of pregnancy. We
      therefore postulate that these polymorphisms predisposed this patient to the
      development of intrahepatic cholestasis within the abnormal pro-inflammatory
      cytokine milieu typical for Hodgkin's lymphoma. This case shows for the first
      time that some polymorphisms in ABCB11 and ATP8B1 may predispose to the
      development of intrahepatic cholestasis in Hodgkin's lymphoma. It also
      demonstrates the importance of close clinical surveillance for the development of
      Hodgkin's lymphoma in patients presenting with unexplained intrahepatic
      cholestasis. 

PMID- 25755489
TI  - Current status of immunosuppression in liver transplantation.
AB  - With advancements in immunosuppressive strategies and availability of better
      immunosuppressive agents, survival rate following liver transplantation has
      improved significantly in the recent times. Besides improvements in surgical
      techniques, the most important factor that has contributed to this better outcome
      is the progress made in the field of immunosuppression. Over the last several
      years, the trend has changed to tailored immunosuppression with the aim of
      achieving optimal graft function while avoiding its undesirable side effects.
      Induction agents are no longer used routinely and the aim is to provide minimal
      immunosuppression in the maintenance phase. The present review discusses the
      various types of immunosuppressive agents, their mechanism of action, clinical
      utility, advantages and disadvantages, and their side effects in short and long
      term. It also discusses about tailoring immunosuppression in presence of various
      situations such as renal dysfunction, metabolic syndrome, hepatitis C recurrence,
      cytomegalovirus infections and so on. The issue of chronic kidney disease and the
      available renal sparing immunosuppressive strategies has been particularly
      stressed upon. Finally, it discusses about the practical aspects of various
      immunosuppression regimens including drug monitoring. 

PMID- 25755491
TI  - Elevated alpha fetoprotein, no hepatocellular carcinoma.
AB  - Alpha fetoprotein is a fetal specific glycoprotein which falls rapidly after
      birth. High level of alpha fetoprotein is suspicious of hepatocellular carcinoma
      but may be elevated in chronic viral hepatitis. A 35-year-old presented to us
      with jaundice for 7 days. He had chronic hepatitis B infection for last 12 months
      and was taking medicines irregularly for same. He had high alpha fetoprotein
      levels (740.9 ng/ml) without evidence of hepatocellular carcinoma which reduced
      with antiviral therapy. Such elevation can be explained due to hepatic
      inflammation and viral replication. 

PMID- 25755492
TI  - Variceal upper gastrointestinal bleeding with long standing Fever and anorexia.

PMID- 25755493
TI  - Reversibility of hepatic fibrosis and cirrhosis-another evidence.

PMID- 25755494
TI  - Hepatobiliary quiz-6 (2013).

PMID- 25755495
TI  - Hepatobiliary quiz-6 (2013).

PMID- 25755496
TI  - Variceal upper gastrointestinal bleeding with long standing Fever and anorexia:
      sarcoidosis of the liver.

PMID- 25755497
TI  - Liver-bud Transplantation: A Bud That May Bloom into the Future of Regenerative
      Medicine.

PMID- 25755498
TI  - Association of Sleep Disorders with Nonalcoholic Fatty Liver Disease (NAFLD): A
      Population-based Study.
AB  - BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is a major cause of chronic
      liver disease. In smaller studies, sleep apnea has been previously associated
      with NAFLD. The aim of this study was to assess the prevalence and independent
      associations of sleep disorders in patients with NAFLD using recent population
      based data. METHODS: Three cycles of the National Health and Nutrition
      Examination Survey (NHANES) conducted between 2005 and 2010 were used. The
      diagnosis of NAFLD was established as elevated liver enzymes in the absence of
      all other causes of chronic liver disease. Sleep disorders were diagnosed using
      sleep disorder questionnaires completed by NHANES participants, and included self
      reported history of sleep apnea, insomnia, and restless leg syndrome. The
      prevalence of sleep disorders was compared between those with and without NAFLD.
      RESULTS: A total of 10,541 adult NHANES participants with complete demographic,
      clinical, and laboratory data were included. Of those, 15.0% had NAFLD and 7.2%
      reported having sleep disorders. Of those with sleep disorders, 64.7% reported
      history of sleep apnea, 16.0% had history of insomnia, and 4.0% had restless leg
      syndrome. Individuals with NAFLD were more likely to be male (53.8% vs. 45.7%, P
      < 0.0001), obese (50.1% vs. 33.4%, P < 0.0001) and had higher prevalence of sleep
      disorders (9.1% vs. 6.9%, P = 0.0118). In multivariate analysis, having any sleep
      disorder, sleep apnea and insomnia were all independently associated with NAFLD
      [OR (95% CI) = 1.40 (1.11-1.76), OR = 1.39 (0.98-1.97), and OR = 2.17 (1.19
      3.95); respectively)]. CONCLUSIONS: This large population-based data suggests
      that NAFLD is associated with sleep disorders. Although the exact mechanism is
      unknown, this association is most likely through metabolic conditions associated
      with NAFLD.

PMID- 25755499
TI  - Higher Prevalence and More Severe Coronary Artery Disease in Hepatitis C Virus
      infected Patients: A Case Control Study.
AB  - BACKGROUND: An association of Coronary artery disease (CAD) with hepatitis C
      (HCV) has been suggested, but definitive data are still lacking. AIM: Our study
      sought to estimate the prevalence and severity of CAD in HCV patients compared to
      with age-, sex-, and race-matched controls without HCV infection. SUBJECTS AND
      METHODS: 63 HCV-infected patients were compared with 63 age, race, and sex
      matched controls without HCV infection undergoing coronary angiography for
      evaluation of CAD. CAD was defined as more than a 50% blockage in any of the
      proximal coronary arteries on angiogram. The severity of the stenosis was defined
      by the modified Reardon severity scoring system: <50% stenosis of the luminal
      diameter, 1 point; 50-74%, 2 points; 75-99%, 3 points; 100% or total obstruction,
      4 points. The points for each lesion in the proximal coronary circulation were
      summed to give the score for severity. RESULTS: A significantly higher prevalence
      of CAD was noted in the HCV population (69.8% vs. 47.6%, = 0.01). The combined
      Reardon's severity score in the HCV group was significantly higher compared to
      the controls (6.26 +/- 5.39 vs. 2.6 +/- 3.03, P < 0.0005). Additionally,
      significant multivessel CAD (>50% stenosis and >=2 vessels involved) was also
      noted significantly more commonly in the HCV group compared to controls (57.1%
      vs. 15.9%, P < 0.0005). CONCLUSION: In this retrospective study the prevalence
      and severity of CAD was higher in HCV patients who were evaluated for CAD by
      angiogram compared with matched non-HCV patients. HCV-positive status is
      potentially a risk factor for CAD.

PMID- 25755500
TI  - Long-term Branched Chain Amino Acid Supplementation Ameliorates
      Diethylnitrosamine-induced Liver Glutathione S-transferase-p Positivity in Zucker
      Fatty Rats.
AB  - BACKGROUND: Obesity increases the risk of fatty liver disease and liver cancer.
      There are several models of obesity-associated hepatocellular carcinoma, but
      tumor development in these models is slow. MATERIALS AND METHODS: We investigated
      Zucker fatty rats, a model of obesity and insulin resistance, to discover if
      diethylnitrosamine (DEN), a potent liver carcinogen, might enhance liver
      carcinogenesis. We also investigated the effect of branched chain amino acids
      (BCAA) against the development of liver cancer. RESULTS: Incidence and number of
      hepatocellular carcinomas and adenomas were significantly greater in DEN-treated
      Zucker fatty rats than in DEN-treated lean rats. All treated Zucker fatty rats
      developed hepatocellular carcinoma within 16 weeks. Long-term BCAA
      supplementation significantly reduced expression of CyclinD1, PCNA, thymidine
      kinase, Bcl-2, and GST-p and increased expression of p21 in the liver.
      Furthermore, BCAA treatment significantly reduced the area of GST-p positive
      foci. CONCLUSION: Long-term BCAA treatment may induces cell cycle arrest and
      apoptotic induction, thus suppressing pre-neoplastic lesions.

PMID- 25755501
TI  - Primary prophylaxis of bleeding from esophageal varices in cirrhosis.
AB  - Prophylaxis of the first bleeding from esophageal varices became a clinical
      option more than 20 years ago, and gained a large diffusion in the following
      years. It is based on the use of nonselective beta-blockers, which decreases
      portal pressure, or on the eradication of esophageal varices by endoscopic band
      ligation of varices. In patients with medium or large varices either of these
      treatments is indicated. In patients with small varices only medical treatment is
      feasible, and in patients with medium and large varices with contraindication or
      side-effects due to beta-blockers, only endoscopic band ligation may be used. In
      this review the rationale and the results of the prophylaxis of bleeding from
      esophageal varices are discussed. 

PMID- 25755502
TI  - Hepatotropic viral infection associated systemic vasculitides-hepatitis B virus
      associated polyarteritis nodosa and hepatitis C virus associated cryoglobulinemic
      vasculitis.
AB  - Two hepatotropic viruses have been shown to have causal relationship with
      systemic vasculitis-hepatitis B with classical polyarteritis nodosa and hepatitis
      C with cryoglobulinemic vasculitis. The present paper provides an updated
      overview on the clinical presentations and management of these vasculitides. HBV
      associated PAN patients have higher weight loss, peripheral neuropathy,
      mononeuritis multiplex, abdominal pain, gastrointestinal manifestations requiring
      surgery, cardiomyopathy, orchitis, hypertension, and/or elevated transaminase
      levels. Microaneurysms are also more common in mesenteric artery. Skin
      manifestations, however are less common. These patients also have a severe
      disease as suggested by higher five factor score and higher BVAS. Though relapses
      are less common, mortality is higher in patients with HBV PAN as compared to non
      HBV PAN. Plasmapheresis has a role in treatment in clearing off immune complexes.
      The common clinical manifestations of HCV associated cryoglobulinemic vasculitis
      are skin lesions, peripheral neuropathy, glomerulonephritis, arthritis, and sicca
      symptoms. Though combination therapy comprising of pegylated interferon alpha and
      ribavirin is the first line of management, immunotherapy is needed for severe or
      life threatening manifestations. Recent randomized trials have shown the efficacy
      of rituximab in such situations. 

PMID- 25755503
TI  - Hepatitis e and acute liver failure in pregnancy.
AB  - Hepatitis E virus is a positive strand RNA virus with three open reading frames
      which is transmitted predominantly through the fecal contamination of water and
      food. It is the most common cause of acute liver failure in endemic areas.
      Pregnant women especially from the Indian subcontinent and Africa are at
      increased risk of contracting acute HEV infection as well as developing severe
      complications including ALF. Transmission of HEV occurs from mother to unborn
      child. Both maternal and fetal complications may occur, including abortion, fetal
      demise, preterm labor and maternal or neonatal death. The precise reasons for
      increased susceptibility to HEV infection during pregnancy and associated severe
      disease are still an enigma. Management is supportive and termination of
      pregnancy is not recommended as a general rule. Prevention of infection is of
      vital importance, as availability of clean drinking water can reduce the burden
      of this disease in the community. There is a need for future research to focus on
      prevention of ALF in pregnancy and to study the disease pathogenesis, which is
      not explicitly understood at present. The availability of a vaccine may alter the
      natural course of the disease in this select population which is at risk. 

PMID- 25755504
TI  - Hepatitis E and Acute-on-Chronic Liver Failure.
AB  - Hepatitis E virus (HEV) is the most common cause of acute viral hepatitis (AVH)
      globally. It causes large scale epidemics of AVH across the low- and middle
      income countries in Asia and Africa, and also causes sporadic cases of AVH in the
      same geographical region. AVH due to HEV is usually an acute, self-limiting
      illness, similar in clinical presentation to AVH caused by hepatitis A virus
      (HAV). When HEV causes AVH in patients of chronic liver disease it may worsen
      rapidly to a syndrome called acute-on-chronic liver failure (ACLF) leading to
      very high mortality. Acute deterioration of liver function in a patient with
      compensated chronic liver disease is the characteristic feature of ACLF. The
      typical disease course of patients with ACLF is the appearance of organ failure,
      which progresses to multi-organ failure and death. Many publications have
      reported HEV as one of the leading causes for ACLF from Asia and Africa, where
      HEV is endemic. The mortality rate of HEV-related ACLF (HEV-ACLF) ranges from 0%
      to 67% with a median being 34%. These patients require admission in the intensive
      care unit and they benefit from a team approach of clinicians with expertise in
      both hepatology and critical care. The goals of treatment are to prevent further
      deterioration in liver function, reverse precipitating factors, and support
      failing organs. Liver transplantation is required in selected patients to improve
      survival and quality of life. One preliminary report suggests that ribavirin may
      be an effective and safe drug for treatment of HEV-ACLF however this requires
      validation in large trials. 

PMID- 25755507
TI  - A case of cutaneous reaction with tenofovir disoproxil fumarate.
AB  - Hypersensitivity reaction to tenofovir consisting of maculopapular rash on the
      face, extremities and trunk has been reported in HIV patients. We report the
      first case in a hepatitis B patient. 

PMID- 25755506
TI  - Liver Transplantation: East versus West.
AB  - Liver transplantation (LT) has evolved rapidly since the first successful liver
      transplant performed in1967. Despite a humble beginning, this procedure gained
      widespread acceptance in the western world as a suitable option for patients with
      end stage liver disease (ESLD) by the beginning of the 1980s. At present,
      approximately 25,000 liver transplants are being performed worldwide every year
      with approximately 90% one year survival. The techniques of living donor liver
      transplantation (LDLT) developed in East Asia in the 1990s to overcome the
      shortage of suitable grafts for children and scarcity of deceased donors. While
      deceased donor liver transplantation (DDLT) constitutes more than 90% of LT in
      the western world, in India and other Asian countries, most transplants are LDLT.
      Despite the initial disparity, outcomes following LDLT in eastern countries have
      been quite satisfactory when compared to the western programs. The etiologies of
      liver failure requiring LT vary in different parts of the world. The commonest
      etiology for acute liver failure (ALF) leading to LT is drugs in the west and
      acute viral hepatitis in Asia. The most common indication for LT due to ESLD in
      west is alcoholic cirrhosis and hepatitis C virus (HCV), while hepatitis B virus
      (HBV) predominates in the east. There is a variation in prognostic models for
      assessing candidature and prioritizing organ allocation across the world. Model
      for end-stage liver disease (MELD) is followed in United States and some European
      centers. Other European countries rely on the Child-Turcotte-Pugh (CTP) score.
      Some parts of Asia still follow chronological order of listing. The debate
      regarding the best model for organ allocation is far from over. 

PMID- 25755505
TI  - MicroRNAs in Liver Disease: Bench to Bedside.
AB  - MicroRNAs (miRs) are small non-coding RNAs that negatively regulate gene
      expression by pairing with partially complementary target sequences in the 3'UTRs
      of mRNAs to promote degradation and/or block translation. Aberrant miR expression
      is associated with development of multiple diseases including hepatic diseases.
      The role of miRs in the regulation of gene expression and rapid progress in the
      field of microRNA research are resulting in momentum toward development of
      diagnostic markers and novel therapeutic strategies for human liver diseases.
      Recent studies provide clear evidence that miRs are abundant in the liver and
      modulate a diverse spectrum of biological functions, thereby supporting an
      association between alterations of miR homeostasis and pathological liver
      diseases. Here we review the role of miRs in liver as their physiological and
      pathological importance has been demonstrated in metabolism, immunity, viral
      hepatitis, oncogenesis, fatty liver diseases (alcoholic and non-alcoholic), drug
      induced liver injury, fibrosis as well as acute liver failure. 

PMID- 25755508
TI  - Budd-Chiari syndrome following laparoscopic cholecystectomy.
AB  - Patients with thrombophilic disorder while undergoing intra-abdominal surgery may
      develop splanchnic vein thrombosis which can have dire consequences. Here we
      report a case of a 38-year-old female who developed acute Budd-Chiari syndrome
      after a laparoscopic cholecystectomy. She had polycythemia vera which was not
      diagnosed before surgery. In this report we want to highlight presurgical
      evaluation of routine biochemical tests and ultrasonography suggestive of
      myeloproliferative disorders were missed which led to the Budd-Chiari syndrome.
      We recommend a meticulous look at the routine evaluation done prior to
      cholecystectomy is essential. 

PMID- 25755509
TI  - Liver space occupying lesion in a patient with secondary immunodeficiency.

PMID- 25755510
TI  - Autophagy and liver disease.

PMID- 25755511
TI  - Hepatobiliary quiz-7 (2013).

PMID- 25755513
TI  - Biomimetic enzyme nanocomplexes: use as antidotes and preventive measures for
      alcohol intoxication.

PMID- 25755512
TI  - Hepatobiliary quiz-7 (2013).

PMID- 25755514
TI  - Patients with Diabetes Mellitus are Prone to Develop Severe Hepatitis and Liver
      Failure due to Hepatitis Virus Infection.
AB  - BACKGROUND: Acute viral hepatitis (AVH) is usually a self-limiting illness.
      Diabetics are prone to develop liver diseases and liver regeneration is impaired
      in them. Natural course of AVH in diabetics has not been assessed and may be
      severe. DESIGN: Observational prospective study to evaluate natural course of AVH
      in patients with and without diabetes mellitus. Consecutive patients with AVH
      were included and categorized in to those with or without diabetes. Etiology,
      complications, mortality and recovery parameters of AVH were identified and
      compared between two groups. RESULTS: 131 consecutive AVH between March 2007 and
      March 2009 were evaluated; 12 diabetics and 83 non-diabetics (n = 95) were
      included for analysis. Hepatitis E was the commonest cause (n = 55, 57.89%) in
      the whole cohort. However, Hepatitis B virus (HBV) as the etiology was
      significantly higher among diabetics than in non-diabetics (58.33% vs. 25.3%, P =
      0.02). In contrast, hepatitis E was the etiology in 61.44% of non-diabetics.
      Frequency of severe hepatitis was significantly higher in diabetics than in non
      diabetics (5/12; 41.67% vs. 9/83; 10.64%, P < 0.005). 5 of 14 (36%) with severe
      hepatitis were diabetics. Liver failure and death occurred in 2 (16%) diabetics,
      while none among the non-diabetics had liver failure. Multiple variable logistic
      regression analysis revealed that acute hepatitis B (OR 4.7 (95% CI 1.34-16.47))
      and diabetes (OR 4.0 (95% CI 0.96-16.47)) were associated with severe hepatitis.
      CONCLUSION: Patients with diabetes are at risk to contact HBV infection and
      severe hepatitis.

PMID- 25755515
TI  - Association of Interleukin-1beta and Gene Polymorphisms with Liver Pathogenesis
      in Hepatitis B Virus Infection among Eastern Indian Population.
AB  - BACKGROUND: Interleukin-1beta (IL-1beta) is an important member of the family of
      the proinflammatory cytokines that modulate outcome of hepatitis B virus (HBV)
      infection. OBJECTIVES: This study was designed to investigate the relationship
      between the polymorphic genotypes of the interleukin-1beta (IL-1beta) promoter
      region and the interleukin-1 receptor antagonist gene (IL-1RN) and disease
      outcome in HBV-infected individuals. METHODS: DNA was extracted from 395 study
      subjects including HBV carriers with varying clinical presentations, as well as
      healthy controls and spontaneously recovered cases (SRC). Polymorphisms in IL
      1beta (at position -511) and IL-1RN (variable nucleotide tandem repeats, VNTR)
      were analyzed by polymerase chain reaction-restriction fragment length
      polymorphism (PCR-RFLP) and PCR based assay respectively. RESULTS: Among the
      study subjects, different IL-1beta (at position -511) (CC, CT and TT) and IL-1RN
      (1/1, 1/2, 2/2 and 1/3) polymorphic genotypes were found at variable proportions.
      Logistic regression analysis revealed, no notable difference at the level of IL
      1beta promoter (P = 0.244; OR = 0.78; 95% CI = 0.52-1.18) or IL-1RN genotype
      polymorphism (P = 0.840; OR = 1.03; 95% CI = 0.78-1.36) among the HBV carriers
      and controls or SRC cases. Pairwise proportion testing showed, IL-1beta -511
      genotype CC was significantly higher among asymptomatic carriers (ASC) in
      comparison with liver cirrhosis (LC) patients (P value = 0.028) and healthy
      control group (P-value = 0.036). IL-1RN genotype 2/2 was considerably higher in
      LC group than SRC as well as control group. Combinations of IL-1beta (-511) and
      IL-1RN polymorphisms were associated with disease progression, such as CC-1/2
      with ASC and TT-2/2 with LC. CONCLUSION: IL-1beta polymorphisms are found to be
      associated with disease severity. Different polymorphic combinations are
      associated with degree of disease severity. Overall this is the first report from
      Eastern India, which shows association of IL-1beta polymorphisms with HBV-related
      hepatic complications.

PMID- 25755516
TI  - Hepatitis B Virus Infection can Cause Hepatocellular Carcinoma in Less Advanced
      Liver Cirrhosis: A Comparative Study of 142 Patients from North India.
AB  - BACKGROUND AND AIMS: The clinical profile of patients with hepatocellular
      carcinoma (HCC) may differ depending on the etiology of HCC. There is no study
      from India comparing the clinical profile of patients of HCC due to hepatitis B
      virus (HBV) infection with other etiologies. METHODS: We retrospectively reviewed
      the records of patients clinically diagnosed as HCC between Nov 2000 and Dec 2012
      admitted under a single unit of Department of Gastroenterology at our hospital.
      We compared the clinical presentation of patients of Hepatitis B virus etiology
      (HBV group) with other etiologies (Non-HBV group). RESULTS: One hundred and forty
      two patients were included (median age 60 years [range 30-83], 92% males). The
      etiology was HBV in 56 (39%) and among the non-HBV group (n = 86, 61%) the
      etiological spectrum was following: alcohol 31 (22%), cryptogenic 26 (18%), HCV
      27 (19%), and miscellaneous 2 (1%). The median age of presentation was
      significantly less for HBV group than in non-HBV (56 [30-77] vs. 62 [42-83]
      years, P < 0.01). Clinical evidence of cirrhosis was significantly less common in
      the HBV group than non-HBV group (74% vs 98%, P < 0.01). HBV group had lower CTP
      score than non-HBV (median CTP score 7 vs 8,P < 0.05). Ascites was more common in
      non-HBV group than HBV group (65% vs 43%, P = 0.018). The BCLC staging was: A
      13%, B 23%, C 35%, and D 29%, and there was no difference in tumor
      characteristics or BCLC staging between HBV or the non-HBV group. CONCLUSIONS:
      HBV is a common cause of HCC in India, accounting for 39% of cases. The tumor
      characteristics of HCC due to HBV is similar to other etiologies, however, HBV
      causes HCC at an earlier age, and in less advanced or even absence of cirrhosis,
      thus further consolidating the directly carcinogenic potential of HBV.

PMID- 25755517
TI  - Seroprevalence and risk factors of hepatitis B and hepatitis C virus infections
      in uttarakhand, India.
AB  - BACKGROUND AND AIMS: Hepatitis B virus (HBV) and hepatitis C virus (HCV)
      infections are a serious global public health problem affecting billions of
      people. A population based serological survey was conducted in Uttarakhand, India
      to determine the prevalence and risk factors of HBV and HCV infections. METHODS:
      A cross-sectional study was conducted to achieve the primary objective of
      estimating the prevalence of HBsAg and anti-HCV seropositivity and to estimate
      the potential risk factors. RESULTS: A total of 495 volunteers completed the
      study questionnaire and underwent blood tests for HBsAg and anti-HCV serology. Of
      these, 339 (68.5%) were males and 156 (31.5%) were females. The mean age of the
      volunteers was 31 +/- 4 years. The overall infection rate was 4.4% (n = 22) in
      the studied population. The seroprevalence of HBsAg was found to be 2.8% (n = 14)
      and of anti-HCV antibodies 1.8% (n = 9), whereas dual infection i.e. HBV and HCV
      infection was seen in 0.2% (n = 1). The overall analysis of risk factors of our
      data showed that persons who have received multiple blood transfusions, history
      of hepatitis among family members, visits to unregistered medical practitioners
      and uneducated people are at more risk for acquiring hepatitis B and hepatitis C
      infection. CONCLUSIONS: The results indicate an intermediate level of endemicity
      of HBV and HCV infection in this geographical area of Uttarakhand. Some
      independent risk factors like blood transfusion, intra familial transmission, and
      visit to unregistered practitioners were identified.

PMID- 25755518
TI  - Acute exacerbation of chronic hepatitis B: the dilemma of differentiation from
      acute viral hepatitis B.
AB  - Exacerbations of chronic hepatitis B are common in endemic countries. Acute
      exacerbation of chronic hepatitis B virus (CHB-AE) causing derangement of liver
      functions may be seen in a flare of HBV in immune clearance phase or as a
      reactivation of HBV in patients with inactive or resolved HBV infection. While
      reactivation of HBV is usually seen in HBsAg positive patients, it is being
      increasingly recognized in patients with apparently resolved HBV infection who do
      not have HBsAg in serum but have IgG antibody to core antigen (anti-HBc) in the
      serum, especially so in patients on chemotherapy, immunosuppressive therapy or
      undergoing hematopoietic stem cell transplantation. In an icteric patient who is
      HBsAg positive, it may be difficult to differentiate CHB-AE from acute viral
      hepatitis B (AVH-B). Both may have similar clinical presentation and even IgM
      anti-HBc, the traditional diagnostic marker of AVH-B, may also appear at the time
      of exacerbation of CHB. The differentiation between CHB-AE and AVH-B is important
      not only for prognostication but also because management strategies are
      different. Most cases of AVH-B will resolve on their own, HBsAg clearance is
      achieved spontaneously in 90-95% of adults and treatment is rarely indicated
      except in the few with severe/fulminant disease. In contrast, in CHB-AE, the
      onset of jaundice may lead to decompensation of liver disease and treatment is
      warranted. The mechanisms of acute exacerbation and the differentiating features
      between AVH-B and CHB-AE are reviewed. 

PMID- 25755519
TI  - Neonatal hemochromatosis.
AB  - Neonatal hemochromatosis is a clinical condition in which severe liver disease in
      the newborn is accompanied by extrahepatic siderosis. Gestational alloimmune
      liver disease (GALD) has been established as the cause of fetal liver injury
      resulting in nearly all cases of NH. In GALD, a women is exposed to a fetal
      antigen that she does not recognize as "self" and subsequently begins to produce
      IgG antibodies that are directed against fetal hepatocytes. These antibodies bind
      to fetal liver antigen and activate the terminal complement cascade resulting in
      hepatocyte injury and death. GALD can cause congenital cirrhosis or acute liver
      failure with and without iron overload and siderosis. Practitioners should
      consider GALD in cases of fetal demise, stillbirth, and neonatal acute liver
      failure. Identification of infants with GALD is important as treatment is
      available and effective for subsequent pregnancies. 

PMID- 25755520
TI  - A review and current perspective on Wilson disease.
AB  - Wilson disease is a rare, inherited autosomal recessive disease of copper
      metabolism and may be more common where consanguinity is prevalent. Much has been
      known about the disease after it was first described by Kinnier Wilson as
      'progressive lenticular degeneration in 1912. Over 500 mutations of the ATP7B
      gene has been identified with no clear genotype to phenotype correlation. Loss of
      ATP7B function leads various grades of reduced biliary excretion of copper and
      reduced incorporation of copper into ceruloplasmin; accumulation and toxicity of
      copper in the liver, brain and other tissues results in liver toxicity and other
      myriad manifestations of the disease. The clinical features may vary from
      asymptomatic state to chronic liver disease, acute liver failure,
      neuropsychiatric manifestations and hemolytic anemia. Diagnosis is based on the
      combination of clinical sign's, biochemical features, histologic findings and
      mutation analysis of ATP7B gene. Subtle geographical differences exist with a
      disproportionate proportion of children presenting with acute liver failure. A
      high index of suspicion is needed for an early diagnosis. Ratios of biochemical
      indices for early diagnosis need validation across geographical regions and may
      not be particularly applicable in children. Better biomarkers or the need for
      tests for early detection of ALF persists. Drugs used in the treatment of Wilson
      disease include copper chelating agents such as d-Penicillamine, trientine and
      zinc salt. Untreated Wilson disease uniformly leads to death from liver disease
      or severe neurological disability. Early recognition and treatment has excellent
      prognosis. Liver transplantation is indicated in acute liver failure and end
      stage liver disease. Family screening in order to detect the disorder in the
      first-degree relatives is warranted. This review provides an overview of
      different aspects of Wilson disease including geographical differences in
      presentations and clinical management and the limitations of currently available
      tests. 

PMID- 25755522
TI  - Peritoneovenous shunt scintigraphy to assess shunt patency in patients with
      refractory ascites.
AB  - Peritoneovenous shunt scintigraphy is an infrequently performed study to non
      invasively assess shunt patency in patients with recurrent or refractory ascites
      in cirrhotic patients. We describe two patients of chronic liver disease in whom
      (99m)Tc-macroaggregated albumin scintigraphy was performed to assess the patency
      of peritoneovenous shunt. Visualization of lung activity was interpreted as
      indicative of shunt patency. While both lungs were visualized almost immediately
      in the first patient, they were visualized by 30 min in the second patient.
      Visualization of radiolabeled peritoneal fluid in the entire length of the shunt
      tubing may be variable, and was seen in only one patient. Scintigraphy also
      helped in excluding communication between the ascites and right groin collection
      in the second patient. 

PMID- 25755521
TI  - Changing pattern of donor selection criteria in deceased donor liver transplant:
      a review of literature.
AB  - During the last couple of decades, with standardization and progress in surgical
      techniques, immunosuppression and post liver transplantation patient care, the
      outcome of liver transplantation has been optimized. However, the principal
      limitation of transplantation remains access to an allograft. The number of
      patients who could derive benefit from liver transplantation markedly exceeds the
      number of available deceased donors. The large gap between the growing list of
      patients waiting for liver transplantation and the scarcity of donor organs has
      fueled efforts to maximize existing donor pool and identify new avenues. This
      article reviews the changing pattern of donor for liver transplantation using
      grafts from extended criteria donors (elderly donors, steatotic donors, donors
      with malignancies, donors with viral hepatitis), donation after cardiac death,
      use of partial grafts (split liver grafts) and other suboptimal donors
      (hypernatremia, infections, hypotension and inotropic support). 

PMID- 25755523
TI  - Splenosis mimicking hepatic adenoma.

PMID- 25755524
TI  - Combination Therapy in Severe Alcoholic Hepatitis-Doesn't Really Work.

PMID- 25755525
TI  - Hepatobiliary quiz-8 (2013).

PMID- 25755526
TI  - Hepatobiliary quiz-8 (2013).

PMID- 25755527
TI  - Hepatitis C virus heterogeneity: lipoprotein and immunoglobulin binding and
      clinical status.

PMID- 25755528
TI  - Prevalence of hepatitis B and C in puducherry.

PMID- 25755529
TI  - Acute Kidney Dysfunction in Patients with Chronic Hepatitis C Virus Infection:
      Analysis of Viral and Non-viral Factors.
AB  - BACKGROUND: Multiple studies have shown a relationship between chronic hepatitis
      C infection and chronic kidney disease. The prevalence, severity, underlying
      etiologies and predictors of acute kidney dysfunction (AKD) events in patients
      with hepatitis C has not been studied. METHODS: We investigated viral and non
      viral factors in the development renal dysfunction in 468 HCV patients
      retrospectively over a period of observation ranging from 3 months to 6 yrs.
      RESULTS: A total of 124 AKD events occurred in 63 patients. On regression
      analysis; gender, race, alcohol abuse, HIV (Human immune deficiency virus)
      status, body mass index, baseline viral load (HCV-PCR), and genotype did not
      predict an event of AKD. Decompensated liver disease, history of IVDU, diabetes
      mellitus and baseline creatinine were independent predictors of AKD. CONCLUSION:
      Development of AKD in patient with hepatitis C virus infection is independent of
      the genotype and viral load at baseline and is mostly predisposed by known
      prevalent factors in patients with hepatitis C such as diabetes, hypertension and
      intravenous drug use. Decompensated liver disease is the single most viral
      related factor that predisposes for AKD.

PMID- 25755530
TI  - HLA DRB1 Alleles Discriminate the Manifestation of Autoimmune Hepatitis as Type 1
      or Type 2 in North Indian Population.
AB  - BACKGROUND: Autoimmune hepatitis is a polygenic disorder of unknown etiology,
      where genetic factors affect the occurrence and clinical phenotype of the
      disease. It has been reported as a rare disease entity in the Indian
      subcontinent. This study was undertaken to investigate the association of HLA
      alleles with autoimmune hepatitis type 1 and type 2 in north Indian population
      and to analyze if distinct human leukocyte antigen (HLA) alleles help in
      characterization of the subtypes of autoimmune hepatitis. METHODS: Sixty-eight
      patients with autoimmune hepatitis and 128 healthy controls were recruited in the
      study. Out of 68 patients, 55 were diagnosed with autoimmune hepatitis type 1 and
      13 with autoimmune hepatitis type 2. The patients and the controls were typed for
      HLA class II alleles by PCR-SSP method. RESULTS: HLA DRB1*04 and DRB1*08 were
      found to be significantly associated with autoimmune hepatitis type 1 in north
      Indian population. It was also observed that DRB1*04, DRB1*13 were significantly
      associated with pediatric autoimmune hepatitis type 1 and DRB1*08 was
      significantly associated with adult autoimmune hepatitis type 1. DRB1*14 was
      significantly associated with autoimmune hepatitis type 2. CONCLUSION: The study
      indicates that autoimmune hepatitis in north Indian population is associated with
      HLA alleles that may help to discriminate the subtypes as autoimmune hepatitis
      type 1 and type 2. The study also highlights the ethnic variations in the Indian
      subcontinent in context to the genetic association of HLA with autoimmune
      diseases.

PMID- 25755531
TI  - Assessment of the Model for End-stage Liver Disease (MELD) Score in Predicting
      Prognosis of Patients with Alcoholic Hepatitis.
AB  - BACKGROUND: Traditionally, Maddrey discriminant function (DF) score has been used
      for stratifying the prognosis of alcoholic hepatitis. Recently, the Model for end
      stage liver disease (MELD) score has been applied to alcoholic hepatitis and some
      investigators consider MELD score as a better prognostic indicator. Another new
      prognostic approach, Lille model has been also suggested to accurately identify
      patients at high risk of death. Therefore, this prospective study was aimed to
      compare MELD, DF, Child-Turcotte-Pugh (CTP) scores and Lille model for predicting
      the short-term mortality in Indian patients with alcoholic hepatitis. METHODS: We
      calculated the DF, CTP, MELD and Lille scores in patients hospitalized with
      alcoholic hepatitis & evaluated if the scores predicted in-hospital mortality.
      RESULTS: A total of 104 patients were enrolled and thirty-two (30.7%) patients
      died during the hospitalization (2-30 days). Admission DF score (OR 1.1, P <
      0.04), CTP (OR 2, P < 0.05) MELD score (OR 2.2, P < 0.005) and first week MELD
      score (OR 1.1, P < 0.05) were independently associated with in-hospital
      mortality. The area under the receiver-operating curve (AUROC) for the admission
      and day 7 MELD score was significantly higher than CTP score and was comparable
      to DF score and Lille model (AUC & 95% CI: 0.97 [0.95-1.0], 0.99 [0.99-1.0], 0.91
      [0.83-0.91] and 0.92 [0.86-0.98] for MELD at admission & day 7, admission DF and
      Lille model, respectively). The MELD score >14 at admission and >12 at day 7 had
      high sensitivity and specificity in predicting short-term mortality (96%, 89% and
      95%, 98% respectively). The cutoff of 0.45 for the Lille model was able to
      identify 79% of the observed deaths, whereas DF score >=32 for DF were able to
      identify 85%. CONCLUSION: MELD score, as a predictive model for assessment of
      short-term mortality in alcoholic hepatitis is better than CTP and comparable to
      DF and Lille model.

PMID- 25755532
TI  - Progressive familial intrahepatic cholestasis.
AB  - Progressive familial intrahepatic cholestasis (PFIC) is a group of rare disorders
      which are caused by defect in bile secretion and present with intrahepatic
      cholestasis, usually in infancy and childhood. These are autosomal recessive in
      inheritance. The estimated incidence is about 1 per 50,000 to 1 per 100,000
      births, although exact prevalence is not known. These diseases affect both the
      genders equally and have been reported from all geographical areas. Based on
      clinical presentation, laboratory findings, liver histology and genetic defect,
      these are broadly divided into three types-PFIC type 1, PFIC type 2 and PFIC type
      3. The defect is in ATP8B1 gene encoding the FIC1 protein, ABCB 11 gene encoding
      BSEP protein and ABCB4 gene encoding MDR3 protein in PFIC1, 2 and 3 respectively.
      The basic defect is impaired bile salt secretion in PFIC1/2 whereas in PFIC3, it
      is reduced biliary phospholipid secretion. The main clinical presentation is in
      the form of cholestatic jaundice and pruritus. Serum gamma glutamyl
      transpeptidase (GGT) is normal in patients with PFIC1/2 while it is raised in
      patients with PFIC3. Treatment includes nutritional support (adequate calories,
      supplementation of fat soluble vitamins and medium chain triglycerides) and use
      of medications to relieve pruritus as initial therapy followed by biliary
      diversion procedures in selected patients. Ultimately liver transplantation is
      needed in most patients as they develop progressive liver fibrosis, cirrhosis and
      end stage liver disease. Due to the high risk of developing liver tumors in PFIC2
      patients, monitoring is recommended from infancy. Mutation targeted
      pharmacotherapy, gene therapy and hepatocyte transplantation are being explored
      as future therapeutic options. 

PMID- 25755533
TI  - Gaucher disease.
AB  - Gaucher disease is the commonest lysosomal storage disease seen in India and
      worldwide. It should be considered in any child or adult with an unexplained
      splenohepatomegaly and cytopenia which are seen in the three types of Gaucher
      disease. Type 1 is the non-neuronopathic form and type 2 and 3 are the
      neuronopathic forms. Type 2 is a more severe neuronopathic form leading to
      mortality by 2 years of age. Definitive diagnosis is made by a blood test-the
      glucocerebrosidase assay. There is no role for histological examination of the
      bone marrow, liver or spleen for diagnosis of the disease. Molecular studies for
      mutations are useful for confirming diagnosis, screening family members and
      prognosticating the disease. A splenectomy should not be performed except for
      palliation or when there is no response to enzyme replacement treatment or no
      possibility of getting any definitive treatment. Splenectomy may worsen skeletal
      and lung manifestations in Gaucher disease. Enzyme replacement therapy (ERT) has
      completely revolutionized the prognosis and is now the standard of care for
      patients with this disease. Best results are seen in type 1 disease with good
      resolution of splenohepatomegaly, cytopenia and bone symptoms. Neurological
      symptoms in type 3 disease need supportive care. ERT is of no benefit in type 2
      disease. Monitoring of patients on ERT involves evaluation of growth, blood
      counts, liver and spleen size and biomarkers such as chitotriosidase which
      reflect the disease burden. Therapy with ERT is very expensive and though
      patients in India have so far got the drug through a charitable access programme,
      there is a need for the government to facilitate access to treatment for this
      potentially curable disease. Bone marrow transplantation is an inferior option
      but may be considered when access to expensive ERT is not possible. 

PMID- 25755535
TI  - Embolization of portosystemic shunt for treatment of recurrent hepatic
      encephalopathy.
AB  - Hepatic encephalopathy in the setting of advanced chronic liver disease, occurs
      following a precipitating factor and generally responds to correction of the
      precipitating factor and anticoma measures. We report the case of a lady with
      Child A cirrhosis who presented with frequent episodes of hepatic encephalopathy
      without any precipitating factors. She was found to be having a large
      portosystemic shunt. The shunt was obliterated by coil embolotherapy following
      which there was no further episodes of encephalopathy. 

PMID- 25755534
TI  - Autophagy modulation as a potential therapeutic target for liver diseases.
AB  - Autophagy is a critical intracellular pathway which maintains cellular function
      by lysosomal degradation of damaged proteins and organelles besides elimination
      of invading pathogens. Its primary function is to prevent cell death. Autophagy
      has diverse physiological functions namely; starvation adaptation, prevention of
      tumorigenesis, energy homeostasis, intracellular quality control and degradation
      of abnormal intracellular protein aggregates. Understanding the molecular
      mechanisms of autophagy has given key insights into the pathogenesis of various
      diseases like Non Alcoholic Steato-Hepatitis, Hepatitis B and C infections, Alpha
      1 antitrypsin deficiency and hepatocellular carcinoma. Pharmacological modulation
      of autophagy may have a therapeutic potential in management of these liver
      diseases. 

PMID- 25755536
TI  - Combined uphill and downhill varices as a consequence of rheumatic heart disease:
      a unique presentation.
AB  - Hemorrhage from downhill varices is a rare manifestation. The etiology of
      downhill varices is due to superior vena cava obstruction while uphill varices
      are secondary to portal hypertension. We report a rare case of 55-year-old female
      with bleeding downhill varices not associated with obstruction or compression of
      superior vena cava, but was due to severe pulmonary artery hypertension secondary
      to chronic rheumatic heart disease. 

PMID- 25755537
TI  - Grave's Disease and Primary Biliary Cirrhosis-An Unusual and Challenging
      Association.
AB  - Jaundice in Grave's diseases is uncommon, but when it does occur, complication of
      thyrotoxicosis (heart failure/infection) or intrinsic liver disease should be
      considered. Grave's disease can cause asymptomatic elevation of liver enzymes,
      jaundice and rarely acute liver failure. It is associated with other autoimmune
      diseases like autoimmune hepatitis, or primary biliary cirrhosis. The cause of
      jaundice in Grave's disease is multifactorial. 

PMID- 25755538
TI  - Pseudoparallel channel sign on ultrasonography in alcoholic hepatitis.

PMID- 25755539
TI  - Preclinical Liver Bud Engineering towards Clinical Target for Liver Diseases.

PMID- 25755540
TI  - Shortcut route for generation of functional hepatocyte cells from human skin
      allogenically for autologous treatment of chronic liver diseases.

PMID- 25755541
TI  - Hepatobiliary quiz-9 (2014).

PMID- 25755544
TI  - The New INASL President: Brilliant and Effective.

PMID- 25755543
TI  - Future of therapy for Hepatitis C in India: A Matter of Accessibility and
      Affordability?

PMID- 25755542
TI  - Hepatobiliary quiz-9 (2014).

PMID- 25755545
TI  - Covert hepatic encephalopathy: does the mini-mental state examination help?
AB  - BACKGROUND/OBJECTIVES: The Mini-Mental State Examination (MMSE) has been utilized
      for the diagnosis of hepatic encephalopathy (HE). However, its threshold of
      abnormality has not been formally tested in patients with cirrhosis and its
      diagnostic/prognostic validity remains unknown. The aim of this study was to
      assess it in a large group of well-characterized outpatients with cirrhosis and
      no overt HE. METHODS: One-hundred-and-ninety-one patients underwent clinical
      assessment, MMSE, electroencephalography (EEG) and paper-and-pencil psychometry
      (PHES); 117 were followed up for 8 +/- 5 months in relation to the occurrence of
      HE-related hospitalizations. RESULTS: On the day of study, 81 patients (42%) had
      abnormal EEG and 67 (35%) abnormal PHES; 103 (60%) had a history of HE. Average
      MMSE was 26.6 +/- 3.5; 22 (19%) patients had abnormal MMSE based on the standard
      threshold of 24. Patients with abnormal EEG/PHES/history of HE had worse MMSE
      performance than their counterparts with normal tests/negative history (25.7 +/-
      4.2 vs. 27.3 +/- 2.7; P < 0.01; 25.5 +/- 3.2 vs. 27.9 +/- 1.8, P < 0.0001; 26.3
      +/- 3.7 vs. 27.4 +/- 2.6, P < 0.05, respectively). Based on the above results,
      MMSE thresholds of 26 and 27 were tested against abnormalities in
      clinical/EEG/PHES indices and significant associations were observed. An MMSE
      threshold of 26 was also a predictor of HE-related hospitalization (Cox-Mantel: P
      = 0.001); patients with MMSE <26 were significantly older than those with MMSE
      >=26 but comparable in terms of liver dysfunction and ammonia levels. When MMSE
      items were considered separately, those which correlated most significantly with
      standard HE indices where spatial orientation and writing. CONCLUSION: In
      conclusion, an MMSE <26 identifies older patients with cirrhosis who are more
      prone to manifest HE signs.

PMID- 25755546
TI  - Metadoxine Versus Placebo for the Treatment of Non-alcoholic Steatohepatitis: A
      Randomized Controlled Trial.
AB  - OBJECTIVE AND DESIGN: The study aimed at assessing the therapeutic efficacy and
      safety of metadoxine versus placebo on the ultrasonographic and histological
      features of non-alcoholic steatohepatitis (NASH). SUBJECTS: 134 subjects with
      biopsy-confirmed NASH were randomized to receive metadoxine 500 mg two times
      daily (n = 75) or placebo (n = 59) added to the standard of care, over 16 weeks.
      EFFICACY ENDPOINTS: Originally, the primary efficacy endpoint was the composite
      of: reduction in the steatosis by >=1 grade, reduction in hepatic necro
      inflammation by >=1 grade and ALT normalization. Since >50% of patients refused
      the second biopsy, it was decided to analyze only the individual parameters.
      RESULTS: There was no significant difference between the treatment and the
      placebo groups in either liver histology or ALT or AST. Overall, as expected both
      groups showed reduction in serum ALT and AST compared to baseline. Compared to
      placebo (9 out 54), patients on metadoxine (34 out of 75) had significantly
      higher rates of improvement in 1-point in steatosis grade on ultrasound (P-value
      <0.001). Safety and tolerability did not differ between treatments. CONCLUSION:
      Metadoxine is not effective in improvement of liver histology or serum ALT or AST
      in patients with NASH. However, there was significant improvement of steatosis
      assessed by ultrasound. To properly estimate the effects on histology and
      transaminases, further studies of longer duration and at higher doses are needed.

PMID- 25755547
TI  - Clinical Profile and Response to Treatment with Pegylated Interferon alpha 2b and
      Ribavirin in Chronic Hepatitis C-A Reappraisal from a Tertiary Care Center in
      Northern India.
AB  - AIM: To assess the clinical profile of 80 chronic hepatitis C patients in a
      tertiary health care center in Northern India and also to study the efficacy and
      tolerability of pegylated interferon (Peg-IFN) alpha 2b and ribavirin therapy in
      a cohort of chronic hepatitis C patients. METHODS: Thirty subjects with chronic
      hepatitis C (CH-C) with genotypes 2 and 3 received Peg-IFN alpha 2b 1.5 MUg/kg
      subcutaneously weekly plus daily ribavirin 800 mg for 24 weeks .Subjects with
      genotype 1 infection received therapy for 48 weeks with ribavirin 1000 mg/day and
      Peg-IFN alpha 2b dose remained the same. The primary end point was the sustained
      viral response (SVR). Drug dosage was modified or temporarily discontinued if
      anemia or bone marrow suppression developed. RESULTS: The clinical profile of
      chronic hepatitis C infected patients showed decompensated cirrhosis in the more
      elderly patients. Genotype 3 was the commonest genotype and was seen in 21 (70%)
      patients. The mean baseline HCV RNA was high. SVR was achieved less commonly with
      genotype 1 than with genotype 2/3. Patients who became negative for HCV RNA at 4
      weeks (rapid virological response or RVR) and 12 weeks (early virological
      response or EVR) of treatment showed significantly higher sustained virological
      response (SVR) rates. Similarly, patients who showed normalization of ALT level
      at 4-weeks and 12-weeks of treatment showed significant high rate of SVR. Overall
      treatment was well tolerated. CONCLUSION: In our region, CHC subjects have high
      viral load and genotype 3 being the most common. Treatment with Peg-IFN alpha 2b
      and ribavirin is effective and well tolerated. Genotype 1 was more resistant to
      the treatment. Patients who achieved RVR and EVR are more likely to achieve SVR.
      Although the numbers of patients in this study was small, considering the paucity
      of data of treatment from India, the data is relevant.

PMID- 25755548
TI  - Consensus Statement of HCV Task Force of the Indian National Association for
      Study of the Liver (INASL). Part I: Status Report of HCV Infection in India.
AB  - Globally, around 150 million people are infected with hepatitis C virus (HCV).
      India contributes a large proportion of this HCV burden. The prevalence of HCV
      infection in India is estimated at between 0.5% and 1.5%. It is higher in the
      northeastern part, tribal populations and Punjab, areas which may represent HCV
      hotspots, and is lower in western and eastern parts of the country. The
      predominant modes of HCV transmission in India are blood transfusion and unsafe
      therapeutic injections. There is a need for large field studies to better
      understand HCV epidemiology and identify high-prevalence areas, and to identify
      and spread awareness about the modes of transmission of this infection in an
      attempt to prevent disease transmission. 

PMID- 25755549
TI  - Consensus Statement of HCV Task Force of the Indian National Association for
      Study of the Liver (INASL). Part II: INASL Recommendations for Management of HCV
      in India.
AB  - The estimated prevalence of hepatitis C virus (HCV) infection in India is between
      0.5 and 1.5% with hotspots showing much higher prevalence in some areas of
      northeast India, in some tribal populations and in certain parts of Punjab.
      Genotype 3 is the most prevalent type of infection. Recent years have seen
      development of a large number of new molecules that are revolutionizing the
      treatment of hepatitis C. Some of the new directly acting agents (DAAs) like
      sofosbuvir have been called game-changers because they offer the prospect of
      interferon-free regimens for the treatment of HCV infection. These new drugs have
      not yet been approved in India and their cost and availability is uncertain at
      present. Till these drugs become available at an affordable cost, the treatment
      that was standard of care for the whole world before these newer drugs were
      approved should continue to be recommended. For India, cheaper options, which are
      as effective as the standard-of-care (SOC) in carefully selected patients, are
      also explored to bring treatment within reach of poorer patients. It may be
      prudent to withhold treatment at present for selected patients with genotype 1 or
      4 infection and low levels of fibrosis (F1 or F2), and for patients who are non
      responders to initial therapy, interferon intolerant, those with decompensated
      liver disease, and patients in special populations such as stable patients after
      liver and kidney transplantation, HIV co-infected patients and those with
      cirrhosis of liver. 

PMID- 25755550
TI  - Nutrition in the management of cirrhosis and its neurological complications.
AB  - Malnutrition is a common feature of chronic liver diseases that is often
      associated with a poor prognosis including worsening of clinical outcome,
      neuropsychiatric complications as well as outcome following liver
      transplantation. Nutritional assessment in patients with cirrhosis is challenging
      owing to confounding factors related to liver failure. The objectives of
      nutritional intervention in cirrhotic patients are the support of liver
      regeneration, the prevention or correction of specific nutritional deficiencies
      and the prevention and/or treatment of the complications of liver disease per se
      and of liver transplantation. Nutritional recommendations target the optimal
      supply of adequate substrates related to requirements linked to energy, protein,
      carbohydrates, lipids, vitamins and minerals. Some issues relating to
      malnutrition in chronic liver disease remain to be addressed including the
      development of an appropriate well-validated nutritional assessment tool, the
      identification of mechanistic targets or therapy for sarcopenia, the development
      of nutritional recommendations for obese cirrhotic patients and liver-transplant
      recipients and the elucidation of the roles of vitamin A hepatotoxicity, as well
      as the impact of deficiencies in riboflavin and zinc on clinical outcomes. Early
      identification and treatment of malnutrition in chronic liver disease has the
      potential to lead to better disease outcome as well as prevention of the
      complications of chronic liver disease and improved transplant outcomes. 

PMID- 25755551
TI  - Pregnancy-related liver disorders.
AB  - Pregnancy-related liver disorders accounted for 8% of all maternal deaths at our
      center from 1999 to 2011. Of the three pregnancy-related liver disorders (acute
      fatty liver of pregnancy (AFLP), HELLP (Hemolysis, elevated liver enzymes, low
      platelets) syndrome and pre-eclamptic liver dysfunction, which can lead to
      adverse maternal and fetal outcome, AFLP is most typically under - diagnosed.
      Risk of maternal death can be minimised by timely recognition and
      early/aggressive multi-specialty management of these conditions. Urgent
      termination of pregnancy remains the cornerstone of therapy for some of these
      life threatening disorders, but recent advancements in our understanding help us
      in better overall management of these patients. This review focuses on various
      aspects of pregnancy-related liver disorders. 

PMID- 25755553
TI  - Melioidosis presenting as Fever and jaundice: a rare presentation.
AB  - Melioidosis caused by the environmental Gram-negative bacillus Burkholderia
      pseudomallei is endemic in northern Australia and Southeast Asia and is being
      described increasingly from south and west coastal regions of India. Melioidosis
      is known to have high mortality (14-50%) and the risk factors associated with it
      are diabetes mellitus and heavy alcohol abuse. Melioidosis primarily presents as
      pneumonia, genitourinary infection and bacteremia. We present a case of
      Melioidosis from North India, a 56-year-old diabetic male, presenting with fever
      and jaundice. His blood culture was positive for the B. pseudomallei. The hepatic
      involvement was in the form of jaundice with serum bilirubin value of more than
      12 mg/dL, hepatic enzymes more than ten times high and without hepatic abscess.
      He improved with intravenous antibiotics with complete normalization of liver
      function tests. 

PMID- 25755552
TI  - Pregnancy with portal hypertension.
AB  - Even though pregnancy is rare with cirrhosis and advanced liver disease, but it
      may co-exist in the setting of non-cirrhotic portal hypertension as liver
      function is preserved but whenever encountered together is a complex clinical
      dilemma. Pregnancy in a patient with portal hypertension presents a special
      challenge to the obstetrician as so-called physiological hemodynamic changes
      associated with pregnancy, needed for meeting demands of the growing fetus,
      worsen the portal hypertension thereby putting mother at risk of potentially life
      threatening complications like variceal hemorrhage. Risks of variceal bleed and
      hepatic decompensation increase many fold during pregnancy. Optimal management
      revolves round managing the portal hypertension and its complications. Thus
      management of such cases requires multi-speciality approach involving
      obstetricians experienced in dealing with high risk cases, hepatologists,
      anesthetists and neonatologists. With advancement in medical field, pregnancy is
      not contra-indicated in these women, as was previously believed. This article
      focuses on the different aspects of pregnancy with portal hypertension with
      special emphasis on specific cause wise treatment options to decrease the
      variceal bleed and hepatic decompensation. Based on extensive review of
      literature, management from pre-conceptional period to postpartum is outlined in
      order to have optimal maternal and perinatal outcomes. 

PMID- 25755554
TI  - Hemophagocytic Lymphohistiocytosis (HLH) in Children Presenting as Liver Disease.
AB  - Hemophagocytic lymphohistiocytosis (HLH) is a rare acute hyperinflammatory
      condition presenting with high fever, pancytopenia, splenomegaly with the
      pathologic finding of hemophagocytic lymphohistiocytosis in bone marrow and other
      tissues. Predominant hepatic manifestations at presentation are rare. We report a
      series of three cases which showcase the spectrum of liver disease as
      presentation in hemophagocytic lymphohistiocytosis. 

PMID- 25755555
TI  - Patient with liver cirrhosis and hemorrhagic ascites.

PMID- 25755556
TI  - Hepatitis C virus genotype 3: hope for nonresponders and patients with cirrhosis.

PMID- 25755557
TI  - Hepatobiliary quiz-10 (2014).

PMID- 25755558
TI  - Hepatobiliary quiz-10 (2014).

PMID- 25755559
TI  - Spontaneous rupture of hepatocellular carcinoma.

PMID- 25755560
TI  - Immortalization of Human Fetal Hepatocyte by Ectopic Expression of Human
      Telomerase Reverse Transcriptase, Human Papilloma Virus (E7) and Simian Virus 40
      Large T (SV40 T) Antigen Towards Bioartificial Liver Support.
AB  - BACKGROUND: Generation of genetically stable and non-tumoric immortalization cell
      line from primary cells would be enormously useful for research and therapeutic
      purposes, but progress towards this goal has so far been limited. It is now
      universal acceptance that immortalization of human fetal hepatocytes based on
      recent advances of telomerase biology and oncogene, lead to unlimited population
      doubling could be the possible source for bioartificial liver device. METHODS:
      Immortalization of human fetal hepatocytes cell line by ectopic expression of
      human telomerase reverse transcriptase (hTERT), human papilloma virus gene (E7)
      and simian virus 40 large T (SV40 T) antigens is main goal of present study. We
      used an inducible system containing human telomerase and E7, both of which are
      cloned into responder constructs controlled by doxycycline transactivator. We
      characterized the immortalized human fetal hepatocyte cells by analysis of green
      fluorescent cells (GFP) positive cells using flow cytometry (FACs) cell sorting
      and morphology, proliferative rate and antigen expression by immunohistochemical
      analysis. In addition to we analysized lactate formation, glucose consumption,
      albumin secretion and urea production of immortalized human fetal hepatocyte
      cells. RESULTS: After 25 attempts for transfection of adult primary hepatocytes
      by human telomerase and E7 to immortalize them, none of the transfection systems
      resulted in the production of a stable, proliferating cell line. Although the
      transfection efficiency was more than 70% on the first day, the vast majority of
      the transfected hepatocytes lost their signal within the first 5-7 days. The
      remaining transfected hepatocytes persisted for 2-4 weeks and divided one or two
      times without forming a clone. After 10 attempts of transfection human fetal
      hepatocytes using the same transfection system, we obtained one stable human
      fetal hepatocytes cell line which was able albumin secretion urea production and
      glucose consumption. CONCLUSION: We established a conditional human fetal
      hepatocytes cell line with mesenchymal characteristics. Thus immortalization of
      human fetal hepatocytes cell line by telomerase biology offers a great challenge
      to examine basic biological mechanisms which are directly related to human and
      best cell source having unlimited population doubling for bioartificial support
      without any risk of replicative senescence and pathogenic risks.

PMID- 25755561
TI  - Association of TNF-alpha Promoter Polymorphism with HBV Associated Disease
      Outcome Among HBV Infected Patients from Orissa, Southern Part of East India.
AB  - BACKGROUND: TNF-alpha promoter polymorphism has been known to be a potential
      predictive factor in patients with HBV infection. We therefore tried to
      investigate whether the TNF-alpha promoter polymorphism at position -238, -857
      and -863 was associated with the outcome of HBV infection in a population from
      Orissa, southern part of East India. METHODS: A total of 195 patients recruited
      for the study were classified into 85 controls and 110 HBV infected cases, which
      included 34 IC, 30 CLD, 32 LC and 14 HCC patients. The polymorphisms at the
      respective sites were detected by a PCR-RFLP followed by statistical analysis.
      RESULTS: The frequency of the genotype -238 GG and the allele -238G in the cases
      (89.0% and 92.7% respectively) was significantly higher than that in the controls
      (68.2% and 82.2% respectively) (P < 0.001, OR = 3.8 and P = 0.001, OR = 2.73).
      Whereas the -238 GA genotype was significantly high in the control group (28.2%)
      when compared to the cases (7.2%) (P < 0.001, OR = 0.2). Similarly, the frequency
      of -863CC and the allele -863C was significantly higher among the cases (24.5%
      and 49.5%) compared to controls (1.17% and 34.7%), (P < 0.001, OR = 27.32 and P =
      0.003, OR = 1.85), whereas the -863CA genotype was significantly high in the
      controls (67.0%) when compared to the cases (50.0%) (P = 0.01, OR = 0.49).
      Haplotype -863C/-857C/-238G in cases was significantly higher than controls (P =
      0.002). Multivariate logistic regression analysis indicates that the genotype 
      863CC bears a negative association with liver disease progression. CONCLUSION:
      The present study established an association of polymorphisms at site -238 and 
      863 of the TNF-alpha promoter with the outcome HBV infection and disease
      progression.

PMID- 25755562
TI  - Hepatitis B immunoglobulin prophylaxis after liver transplantation: experience in
      a tertiary transplant centre.
AB  - BACKGROUND: Prophylaxis with hepatitis B immunoglobulin (HBIG) and nucleoside
      analogs can prevent hepatitis B virus (HBV) recurrence after liver transplant
      (LT). AIM: To determine the efficacy and cost of maintaining immunoprophylaxis
      with HBIG and hyperimmune plasma (HIP) for 6 months after LT. MATERIAL & METHODS:
      The study included 22 HBV related LT recipients who were on entecavir and either
      HBIG or HIP for 6 months. Post transplant HBIG or HIP dose and cost incurred
      towards prophylaxis were noted. The cost of 200 IU of HBIG at the time of study
      was Rs 8250/- (US Dollars 135) and that of 2000 IU of HIP was Rs 8000/- (USD
      130.7). The loading and maintenance costs at end of 6 months were compared
      between the two groups. Response to HBIG and HIP was assessed by checking for
      HBsAg reactivity, anti HBs titer response and HBV DNA viral load. STATISTICAL
      ANALYSIS: Median and range, Kruskal Wallis (KW) sign rank Sum Test and
      Correlation Coefficient (r2) was used for analysis. RESULTS: Thirteen recipients
      received HBIG and 9 recipients HIP. The anti HBs response to HIP was
      significantly high compared to HBIG (KW Sign rank Sum test P < 0.05); titers
      remained high until the study period. Between 8 and 30 days, the titer achieved
      by both HBIG and HIP was similar (KW Sign rank Sum test not significant). Despite
      low anti HBs titer of <100 IU/L, none of the recipients on HBIG had HBsAg
      reactivity while 3 on HIP had transient HBsAg positivity. The total cost with
      HBIG was 13.9 times the cost of HIP. CONCLUSION: HIP immunoprophylaxis in
      combination with entecavir achieves a high anti HBs titer at a significant low
      cost during anhepatic and loading phase. HBV reactivation rates with HBIG and HIP
      is low despite low anti HBs titer.

PMID- 25755563
TI  - Hepatitis C virus treatment in the 'real-world': how well do 'real' patients
      respond?
AB  - BACKGROUND: Published clinical trials of the treatment of HCV are largely
      multicentre prospective pharmaceutical trials. Patients in clinical trials tend
      to have more favorable outcomes than patients in the 'real-world', due to strict
      patient selection and differences in treatment conditions and available
      resources. OBJECTIVES: To assess the outcomes of Hepatitis C infected patients
      treated at the Barwon Health Liver Clinic with combination Pegylated interferon
      (PEG-IFN) and Ribavirin (RBV) therapy and to determine factors associated with a
      treatment response. METHODS: Retrospective review of patients who received
      treatment for Hepatitis C at our institution's Liver Clinic from January 2001
      September 2011. Patient demographics, comorbidities, treatment-related parameters
      and side effects were extracted from medical records and analyzed. RESULTS: A
      total of 190 patients (120 male, 70 female) with a mean age of 42.8 years (range
      20-68 years) commenced treatment. The most common genotype was genotype 3
      (48.9%), followed by genotype 1 (42.6%). 150 of 190 patients (78.9%) completed
      treatment and had end of treatment data available. 107 of 182 patients, (58.8%)
      for whom sustained virologic response (SVR) rate data was available achieved an
      SVR. Overall response rates were; 46.9%, 68.8% and 62.4% in genotypes 1, 2 and 3
      respectively. The response rate was significantly lower in 29 patients with
      documented cirrhosis (20.7%). Age, diabetes and alcohol abuse did not predict
      treatment response in our cohort. Side effects reported in 81.6% of patients
      included general malaise, hematological disturbance and psychiatric issues, and
      necessitated cessation of therapy in 16 patients (8.4%) and dose reduction in 26
      patients (13.7%). CONCLUSIONS: Response rates to combination PEG-IFN and RBV
      therapy at our institution are comparable to other 'real-world' and
      pharmaceutical registration trials. Side effects of combination therapy were
      prominent but resulted in fewer discontinuations of therapy compared to
      pharmaceutical trials.

PMID- 25755564
TI  - Role of mycophenolate mofetil for the treatment of autoimmune hepatitis-an
      observational study.
AB  - BACKGROUND: Eighty percent (80%) of patients with Autoimmune hepatitis (AIH)
      respond to a combination of prednisolone and Azathioprine (AZA). Choice of
      treatment is limited for those who do not respond to this standard therapy. We
      evaluated the role of Mycophenolate mofetil (MMF) as a second line therapy in
      AIH. METHOD: A retrospective observational study was carried out on all patients
      who received MMF for AIH. RESULTS: Twenty out of 117 patients with AIH received
      MMF due to AZA intolerance (18 patients) or refractory disease (2 patients).
      Median age of the study patients was 56 (18-79) years, Male, n = 3 (15%) and
      Female, n = 18 (85%). After a median follow-up period of 47 (5-83) months, 14
      (73.6%) patients were still on MMF with biochemical remission, including 4 out of
      5 patients with cirrhosis. One patient was lost to follow-up. Three patients were
      intolerant of MMF due to adverse events, and two had disease refractory to MMF.
      Both these patients with refractory disease to MMF were initially unresponsive to
      AZA therapy. CONCLUSION: MMF is a safe second line agent in patients with
      autoimmune hepatitis including those with cirrhosis.

PMID- 25755565
TI  - Accuracy of Rapid Point-of-Care Diagnostic Tests for Hepatitis B Surface Antigen
      A Systematic Review and Meta-analysis.
AB  - BACKGROUND: Rapid point-of-care tests provide plausible diagnostic strategy for
      hepatitis B surface antigen (HBsAg) in low resource areas. However, their utility
      depends upon their overall performance. Our objective was to meta-analyze the
      diagnostic accuracy of rapid point-of-care tests for HBsAg. METHODS: Literature
      search was done with the help of a metasearch engine Metta, a query interface for
      retrieving articles from five leading medical databases. Studies that employed
      rapid point-of-care tests for detection of HBsAg and compared the results with
      reference test were included. Two reviewers performed quality assessment of the
      studies and extracted data for estimating test accuracy. Twenty-seven studies
      were meta-analyzed and stratified by multiple parameters. RESULTS: Twenty-seven
      studies had evaluated 49 test brands and generated 76 data points. Sensitivity of
      individual tests varied widely and were heterogeneous (range 43.5%-99.8%); while
      specificity estimates were more robust and close to 100% (range 90%-100%).
      Overall pooled sensitivity, specificity, positive likelihood ratio (LR), negative
      LR and diagnostic odds ratio for all tests were 97.1% (95% CI, 96.1%-97.9%),
      99.9% (CI, 99.8%-100%), 118.4 (CI, 84.7-165.5), 0.032 (CI, 0.023-0.045) and
      4094.7 (CI, 2504.1-6600.8) respectively. This suggested high pooled accuracy for
      all studies. We found substantial heterogeneity between studies. Three factors
      (study location, reference standard and study score) appeared most strongly
      associated with test estimates and observed heterogeneity. The Determine test
      showed consistency in performance in studies done across developed and developing
      countries and the Determine and the BinaxNOW tests had significantly higher
      estimates than pooled estimates of remaining tests. Tests revealed analytical
      sensitivity of 4 IU/ml against manufacturer's claim of 0.5 IU/ml; reduced
      sensitivity with HBsAg mutants and poor performance in seroconversion panels.
      CONCLUSIONS: Tests with better analytical sensitivity need to be developed and
      their feasibility and outcomes in various clinical settings need to be addressed.

PMID- 25755566
TI  - Designing immune therapy for chronic hepatitis B.
AB  - Presently-available antiviral drugs may not be a satisfactory option for
      treatment of patients with chronic hepatitis B (CHB). In spite of presence of
      several antiviral drugs, sustained off-treatment clinical responses are not
      common in CHB patients treated with antiviral drugs. In addition, antiviral drug
      treatment may have limited effects on blocking the progression of HBV-related
      complications. However, substantial long-term risk of viral resistance and drug
      toxicity are related with maintenance antiviral therapy in CHB patients with
      presently-available antiviral agents. The infinite treatments with antiviral
      drugs for CHB patients are also costly and may be unbearable by most patients of
      developing and resource-constrained countries. In this situation, there is
      pressing need to develop new and innovative therapeutic approaches for patients
      with chronic hepatitis B virus (HBV) infection. Immune therapy has emerged as an
      alternate therapeutic approach for CHB patients because studies have shown that
      host immunity is either impaired or derailed or distorted or diminished in CHB
      patients compared to patients with acute resolved hepatitis B who contain the HBV
      replication and control liver damages. Both non antigen-specific immune
      modulators and HBV antigen-specific agents have been used in CHB patients during
      last three decades. However, similar to antiviral therapy, the ongoing regimens
      of immune therapeutic approaches have also been unable to show real promises for
      treating CHB patients. The concept of immune therapy for treating CHB patients
      seems to be rationale and scientific, however, concerns remain about suitable
      designs of immune therapy for CHB patients. 

PMID- 25755567
TI  - Idiopathic Non-Cirrhotic Intrahepatic Portal Hypertension (NCIPH)-Newer Insights
      into Pathogenesis and Emerging Newer Treatment Options.
AB  - Chronic microangiopathy of portal venules results in idiopathic non-cirrhotic
      intrahepatic portal hypertension (NCIPH). Recent data suggest a role for
      vasoactive factors of portal venous origin in the pathogenesis of this 'pure'
      vasculopathy of the liver. Enteropathies (often silent), are an important
      'driver' of this disease. NCIPH is under-recognized and often mis-labeled as
      cryptogenic cirrhosis. Liver biopsy is needed to prove the diagnosis of NCIPH. In
      these patients, with advancing disease and increased porto-systemic shunting, the
      portal venous vasoactive factors bypass the liver filter and contribute to the
      development of pulmonary vascular endothelial disorders-porto-pulmonary
      hypertension and hepato-pulmonary syndrome as well as mesangiocapillary
      glomerulonephritis. Prognosis in NCIPH patients is determined by presence,
      recognition and management of associated disorders. With better understanding of
      the pathogenesis of NCIPH, newer treatment options are being explored. Imbalance
      in ADAMTS 13 (a disintegrin and metalloprotease with thrombospondin type 1 motif,
      member 13): vWF (von-Willebrand factor) ratio is documented in NCIPH patients and
      may have a pathogenic role. Therapeutic interventions to correct this imbalance
      may prove to be important in the management of NCIPH. 

PMID- 25755568
TI  - Mesenteric venous thrombosis.
AB  - Mesenteric vein thrombosis is increasingly recognized as a cause of mesenteric
      ischemia. Acute thrombosis commonly presents with abdominal pain and chronic type
      with features of portal hypertension. Contrast enhanced CT scan of abdomen is
      quite accurate for diagnosing and differentiating two types of mesenteric venous
      thrombosis. Prothrombotic state, hematological malignancy, and local abdominal
      inflammatory conditions are common predisposing conditions. Over the last decade,
      JAK-2 (janus kinase 2) mutation has emerged as an accurate biomarker for
      diagnosis of myeloproliferative neoplasm, an important cause for mesenteric
      venous thrombosis. Anticoagulation is the treatment of choice for acute
      mesenteric venous thrombosis. Thrombolysis using systemic or transcatheter route
      is another option. Patients with peritoneal signs or refractory to initial
      measures require surgical exploration. Increasing recognition of mesenteric
      venous thrombosis and use of anticoagulation for treatment has resulted in
      reduction in the need for surgery with improvement in survival. 

PMID- 25755569
TI  - Terbinafine induced liver injury: a case report.
AB  - Drug induced liver injury (DILI) is a cause of significant morbidity; timely
      diagnosis is important and requires a high index of suspicion. Terbinafine
      induced liver injury is rare. We report a case of Terbinafine induced hepatitis
      cholestatic injury. The patient had a prolonged recovery phase lasting 3 months
      after discontinuation of drug. 

PMID- 25755570
TI  - Abnormality in hepatobiliary scintigraphy in a liver transplant recepient.

PMID- 25755571
TI  - Gut microbiome and liver diseases.
AB  - Nan Qin(1,2), Fengling Yang(1), Ang Li(1), Edi Prifti(3), Yanfei Chen(1), Li
      Shao(1,2), Jing Guo(1), Emmanuelle Le Chatelier(3), Jian Yao(1,2), Lingjiao
      Wu(1), Jiawei Zhou(1), Shujun Ni(1), Lin Liu(1), Nicolas Pons(3), Jean Michel
      Batto(3), Sean P. Kennedy(3), Pierre Leonard(3), Chunhui Yuan(1), Wenchao
      Ding(1), Yuanting Chen(1), Xinjun Hu(1), Beiwen Zheng(1,2), Guirong Qian(1), Wei
      Xu(1), S. Dusko Ehrlich(3,4), Shusen Zheng(2,5) and Lanjuan Li(1,2) Alterations
      of the human gut microbiome in liver cirrhosis. Nature. 2014 Jul 23 [Epub ahead
      of print]. (1) State Key Laboratory for Diagnosis and Treatment of Infectious
      Disease, The First Affiliated Hospital, College of Medicine, Zhejiang University,
      310003 Hangzhou, China; (2) Collaborative Innovation Center for Diagnosis and
      Treatment of Infectious Diseases, Zhejiang University, 310003 Hangzhou, China;
      (3) Metagenopolis, Institut National de la Recherche Agronomique, 78350 Jouy en
      Josas, France; (4) King's College London, Centre for Host-Microbiome
      Interactions, Dental Institute Central Office, Guy's Hospital, London Bridge,
      London SE1 9RT, UK; (5) Key Laboratory of Combined Multi-organ Transplantation,
      Ministry of Public Health, the First Affiliated Hospital, Zhejiang University,
      310003 Hangzhou, China. 

PMID- 25755572
TI  - Hepatobiliary quiz 11 (2014).

PMID- 25755573
TI  - Bile leak leading to lesser sac bile collection masquerading as stomach in
      hepatobiliary scintigraphy.

PMID- 25755574
TI  - Macrophages from patients with cirrhotic ascites showed function alteration of
      host defense receptor.
AB  - BACKGROUND: Patients with cirrhotic ascites (PCA) are susceptible to spontaneous
      bacterial peritonitis (SBP) which has increased morbidity and mortality. Since
      some host defense aspects of peritoneal macrophages (PMf) from PCA are altered
      this study examined factors related to receptor-mediated phagocytosis. METHODS:
      Twelve PCA were studied. PMphi were isolated from ascitic fluid (AF) samples
      removed from these patients. Uptake of mannose receptor (MR)-specific ligand,
      fluorescein isothiocyanate-mannosylated-bovine serum albumin (FITC-man-BSA), by
      patients' PMphi and controls, a human monocytic cell line, was measured pre- and
      post-IL-4 treatment. Phagocytosis of FITC-labeled yeast particles by patients'
      PMphi was measured pre- and post-IL-4 treatment. Fluorescence values were
      obtained using a spectrofuorometer. MRC1 gene was analyzed in blood samples from
      PCA and controls, healthy donors, using standard polymerase chain reaction (PCR)
      technique. RESULTS: Past SBP episode(s) were reported in 58.3% of patients. Mean
      AF volume analyzed per patient was 1.3L. PMphi ratio in cell yield was 53.73% (SD
      18.1). Mean uptake absorbance of patients' PMf was 0.0841 (SD 0.077) compared to
      0.338 (SD 0.34) of controls, P = 0.023. Following IL-4 treatment absorbance
      increased to 0.297 (SD 0.28) in patients' PMf (P = 0.018 on paired sample t
      test), and to 0.532 (SD 0.398 in controls (P = 0.053 on independent sample t
      test). Mean phagocytosis absorbance of patients' PMf was 0.1250 (SD 0.032) before
      IL-4 treatment compared to 0.2300 (SD 0.104) after (P = 0.026). PCR analysis for
      MRC1 gene was negative in all PCA samples compared to positive results in all
      controls. CONCLUSION: Since decreased phagocytosis and MR uptake were enhanced
      post-IL-4 treatment MR downregulation pre-treatment is plausible. Negative PCR
      results for MRC1 might suggest an anomaly, but this awaits further ellucidation.
      These altered host defense findings are relevant to infection pathophysiology,
      and their relevance to SBP susceptibility in PCA is worth verifying.

PMID- 25755575
TI  - Sustained virological response rates to antiviral therapy in genotype 1 and 3
      chronic hepatitis C patients: a study from north India.
AB  - BACKGROUND: In India, both genotype 3 and 1 are predominant genotypes in patients
      with chronic hepatitis C (CHC). However, there is scanty data on sustained viral
      response (SVR) rate with conventionally recommended dual therapy with PEG-IFN and
      ribavirin. METHODS: In this retrospective study, consecutive patients of CHC of
      genotypes 1 and 3, attending the single unit of Gastroenterology of our hospital,
      who received PEG-IFN and ribavirin therapy, were included. Patients who had co
      infection with HIV or HBV were excluded. RESULTS: A total of 114 patients were
      included in the study median age 44 (15-72) years, 79% males. Most common
      presentation was with chronic hepatitis, while 10 (9%) patients had compensated
      cirrhosis. Nine (8%) patients had associated diabetes, 16 (14%) patients gave
      history of significant alcohol abuse. The median baseline HCV RNA level was 3.0 *
      10(5) (1.7 * 10(3)-1.8 * 10(7)) IU/mL. The most common genotype was 3 (75%)
      followed by genotype 1 (25%). 70% patients received PegIFN-alpha2a (median dose
      180 MIU/wk) and 30% patients received PegIFN-alpha2b (median dose 80 MIU/wk). The
      median ribavirin dose was 800 (range 800-1200) mg. SVR in genotype 1 was 64%
      (18/28) while SVR in genotype 3 was 73% (63/86). The factors predicting SVR on
      univariate analysis were a lower baseline HCV RNA level (less than 3.0 * 10(5)),
      higher hemoglobin level > 11.8 g/dl, and achievement of rapid virological
      response (RVR), early virological response (EVR) and end of treatment response
      (ETR). In multivariate analysis the only baseline factor found independently
      correlating with SVR was low HCV RNA level (<3.0 * 10(5) IU/mL) (P = 0.003).
      CONCLUSION: In north India, HCV genotype 3 has a SVR rate of 73%, which is
      comparable to genotype 1 with SVR rate of 64% when treated with PEG-IFN and
      ribavirin therapy. A baseline HCV RNA level lower than 3.0 * 10(5) best predicts
      SVR in addition to achievement of RVR, EVR or ETR.

PMID- 25755576
TI  - Protective Effects of Norursodeoxycholic Acid Versus Ursodeoxycholic Acid on
      Thioacetamide-induced Rat Liver Fibrosis.
AB  - BACKGROUND/OBJECTIVES: Effects of norursodeoxycholic acid (norUDCA) and
      ursodeoxycholic acid (UDCA) on liver fibrosis progression and liver fibrosis
      reversal in thioacetamide (TAA)-treated rats were studied. METHODS: Advanced
      liver fibrosis was induced by TAA treatment (200 mg/kg, i.p.) for 12 weeks. In
      the second experiment resolution of liver fibrosis was assessed after 8 weeks of
      TAA withdrawal. During 8 last weeks of each trial, fibrotic rats were daily
      administered with UDCA (80 mg/kg) and norUDCA (equimolar to 80 mg/kg of UDCA) by
      oral gavage. Liver fibrosis was assessed by Sirius red staining, liver
      hydroxyproline and serum fibrosis markers determination. RESULTS: The TAA
      treatment resulted in advanced fibrosis and increase in liver hydroxyproline
      content and serum fibrosis markers. These signs of fibrosis were less pronounced
      in rats after TAA withdrawal. Treatment with of norUDCA significantly decreased
      the total and relative liver hydroxyproline contents in rats with fibrosis
      reversal, whereas UDCA did not change these parameters. Both compounds decreased
      serum TGFbeta and type IV collagen contents, whereas other serum markers did not
      differ from the placebo group. In the fibrosis progression model the square of
      connective tissue was decreased by norUDCA. Serum type IV collagen and
      procollagen III-NT contents in these experiments were lowered by both UDCA and
      norUDCA, whereas rest of serum fibrosis markers were diminished only by norUDCA.
      CONCLUSIONS: Both norUDCA and UDCA showed therapeutic and prophylactic
      antifibrotic effect in rats with TAA-induced liver fibrosis. For most of tested
      parameters norUDCA was more effective than UDCA, especially in the experiment
      with liver fibrosis regression.

PMID- 25755577
TI  - Role of human albumin in the management of complications of liver cirrhosis.
AB  - Albumin is a negatively charged, relatively small protein synthesized by liver
      cells. Is the most abundant protein in extracellular fluid and accounts for about
      70% of the plasma colloid osmotic pressure. Therefore it plays a crucial role in
      regulating fluid distribution in the body. In addition, albumin possesses
      functional domains with important non-oncotic properties, such as potent anti
      oxydant and scavenging activities, binding of highly toxic reactive metal species
      and a great amount of endogenous and exogenous substances. We have recently
      learned that albumin in cirrhosis undergoes a number of post-transcriptional
      changes that greatly impair its non-oncotic properties. The overall assessment of
      these changes clearly shows that the relative abundance of the native form of
      albumin is significantly reduced in hospitalized patients with cirrhosis and that
      these abnormalities worsen in parallel with the increasing severity of the
      disease. Thus, it is time to abandon the concept of serum albumin concentration
      and refer to the effective albumin concentration, that is the native intact
      albumin. Given the pathophysiological context in which we use human albumin in
      patients with cirrhosis, who are characterized by peripheral vasodilation and a
      low-grade but sustained inflammatory state, the use of albumin in patients with
      cirrhosis should aim at enhancing effective hypovolemia and exploiting its
      antioxidant and scavenging activities. The indications for the use of albumin in
      cirrhosis that clearly emerge from evidence-based medicine are represented by
      conditions characterized by an acute aggravation of effective hypovolemia and
      inflammation, such as such post-paracentesis circulatory dysfunction, spontaneous
      bacterial peritonitis, and hepatorenal syndrome. Other indications to the use of
      albumin that still require further studies are represented by bacterial
      infections other than spontaneous bacterial peritonitis, hepatic encephalopathy
      and long-term treatment of ascites, which has been debated for the last half
      century. 

PMID- 25755578
TI  - Tackling the Hepatitis B Disease Burden in India.
AB  - Globally, approximately 240 people have been infected worldwide with hepatitis B
      Virus (HBV). India has approximately HBV carrier rate of 3.0% with a high
      prevalence rate in the tribal population. With a population of more than 1.25
      billion, India has more than 37 million HBV carriers and contributes a large
      proportion of this HBV burden. While horizontal transmission in childhood appears
      to be a major route of transmission, the role of vertical transmission is
      probably underestimated. Blood transfusion and unsafe therapeutic injections
      continue to be important modes of transmission of HBV. There is a need for large
      field studies to better understand HBV epidemiology and identify high prevalence
      areas, and public health measures to prevent disease transmission and decrease
      the burden of the disease. 

PMID- 25755579
TI  - Portal vein thrombosis in cirrhosis.
AB  - Portal vein thrombosis (PVT) is being increasingly recognized in patients with
      advanced cirrhosis and in those undergoing liver transplantation. Reduced flow in
      the portal vein is probably responsible for clotting in the spleno-porto
      mesenteric venous system. There is also increasing evidence that
      hypercoagulability occurs in advanced liver disease and contributes to the risk
      of PVT. Ultrasound based studies have reported a prevalence of PVT in 10-25% of
      cirrhotic patients without hepatocellular carcinoma. Partial thrombosis of the
      portal vein is more common and may not have pathophysiological consequences.
      However, there is high risk of progression of partial PVT to complete PVT that
      may cause exacerbation of portal hypertension and progression of liver
      insufficiency. It is thus, essential to accurately diagnose and stage PVT in
      patients waiting for transplantation and consider anticoagulation therapy.
      Therapy with low molecular weight heparin and vitamin K antagonists has been
      shown to achieve complete and partial recanalization in 33-45% and 15-35% of
      cases respectively. There are however, no guidelines to help determine the dose
      and therapeutic efficacy of anticoagulation in patients with cirrhosis.
      Anticoagulation therapy related bleeding is the most feared complication but it
      appears that the risk of variceal bleeding is more likely to be dependent on
      portal pressure rather than solely related to coagulation status. TIPS has also
      been reported to restore patency of the portal vein. Patients with complete PVT
      currently do not form an absolute contraindication for liver transplantation.
      Thrombectomy or thromboendovenectomy is possible in more than 75% of patients
      followed by anatomical end-to-end portal anastomosis. When patency of the portal
      vein and/or superior mesenteric vein is not achieved, only non-anatomical
      techniques (reno-portal anastomosis or cavo-portal hemitransposition) can be
      performed. These techniques, which do not fully reverse portal hypertension, are
      associated with higher morbidity and mortality risks in the short term. 

PMID- 25755582
TI  - Wild mushroom poisoning in north India: case series with review of literature.
AB  - Mushroom is an important constituent of diet in many ethnic tribes in India.
      Ethnic Indian tribes are known to consume nearly 283 species of wild mushrooms
      out of 2000 species recorded world over. Although they are experts in
      distinguishing the poisonous from edible mushrooms, yet occasional cases of
      toxicity are reported due to accidental consumption of poisonous mushrooms. We
      report amanita like toxicity in a family after consumption of wild mushrooms
      resulting in fatal outcome. 

PMID- 25755580
TI  - Sinusoidal obstruction syndrome (hepatic veno-occlusive disease).
AB  - Hepatic sinusoidal obstruction syndrome (SOS) is an obliterative venulitis of the
      terminal hepatic venules, which in its more severe forms imparts a high risk of
      mortality. SOS, also known as veno-occlusive disease (VOD), occurs as a result of
      cytoreductive therapy prior to hematopoietic stem cell transplantation (HSCT),
      following oxaliplatin-containing adjuvant or neoadjuvant chemotherapy for
      colorectal carcinoma metastatic to the liver and treated by partial hepatectomy,
      in patients taking pyrrolizidine alkaloid-containing herbal remedies, and in
      other particular settings such as the autosomal recessive condition of veno
      occlusive disease with immunodeficiency (VODI). A central pathogenic event is
      toxic destruction of hepatic sinusoidal endothelial cells (SEC), with sloughing
      and downstream occlusion of terminal hepatic venules. Contributing factors are
      SEC glutathione depletion, nitric oxide depletion, increased intrahepatic
      expression of matrix metalloproteinases and vascular endothelial growth factor
      (VEGF), and activation of clotting factors. The clinical presentation of SOS
      includes jaundice, development of right upper-quadrant pain and tender
      hepatomegaly, ascites, and unexplained weight gain. Owing to the potentially
      critical condition of these patients, transjugular biopsy may be the preferred
      route for liver biopsy to exclude other potential causes of liver dysfunction and
      to establish a diagnosis of SOS. Treatment includes rigorous fluid management so
      as to avoid excessive fluid overload while avoiding too rapid diuresis or
      pericentesis, potential use of pharmaceutics such as defibrotide, coagulolytic
      agents, or methylprednisolone, and liver transplantation. Proposed strategies for
      prevention and prophylaxis include reduced-intensity conditioning radiation for
      HSCT, treatment with ursodeoxycholic acid, and inclusion of bevacizumab with
      oxaliplatin-based chemotherapeutic regimes. While significant progress has been
      made in understanding the pathogenesis of SOS and in mitigating against its
      adverse outcomes, this condition remains a serious complication of a selective
      group of medical treatments. 

PMID- 25755583
TI  - Hydatid Cyst of Liver Presented as Obstructive Jaundice in Pregnancy; Managed by
      PAIR.
AB  - Incidence of Hydatid disease in pregnancy ranges from 1in 20,000 to 1 in 30,000.
      The most common site of hydatid cysts is the liver. The diagnosis of liver
      hydatid cysts is not difficult but the management during pregnancy is
      problematic. Both medical and surgical treatments are available but there is no
      consensus and each case has to be individualized. We present a case of liver
      hydatid cyst presented with obstructive jaundice during pregnancy which was
      managed by Puncture of the cyst under USG guidance; Aspiration of the cystic
      fluid, Injection of hypertonic saline, and Re-aspiration of solution without
      drainage (PAIR) and albendazole therapy. Very few cases of liver hydatosis were
      reported previously which had been managed by PAIR. 

PMID- 25755581
TI  - Infections after orthotopic liver transplantation.
AB  - Opportunistic infections are a leading cause of morbidity and mortality after
      orthotopic liver transplantation. Systemic immunosuppression renders the liver
      recipient susceptible to de novo infection with bacteria, viruses and fungi post
      transplantation as well to reactivation of pre-existing, latent disease.
      Pathogens are also transmissible via the donor organ. The time from
      transplantation and degree of immunosuppression may guide the differential
      diagnosis of potential infectious agents. However, typical systemic signs and
      symptoms of infection are often absent or blunted after transplant and a high
      index of suspicion is needed. Invasive procedures are often required to procure
      tissue for culture and guide antimicrobial therapy. Antimicrobial prophylaxis
      reduces the incidence of opportunistic infections and is routinely employed in
      the care of patients after liver transplant. In this review, we survey common
      bacterial, fungal, and viral infections after orthotopic liver transplantation
      and highlight recent developments in their diagnosis and management. 

PMID- 25755584
TI  - An elderly man with a huge liver.

PMID- 25755585
TI  - Potential newer therapeutic targets for hepatitis B virus drug development.

PMID- 25755586
TI  - Hepatobiliary quiz-12 (2014).

PMID- 25755587
TI  - Giant hemangioma causing budd-Chiari syndrome.

PMID- 25755588
TI  - Portal cavernoma cholangiopathy.

PMID- 25755589
TI  - Portal cavernoma cholangiopathy - history, definition and nomenclature.
AB  - Biliary changes secondary to portal hypertension, especially in portal cavernoma
      secondary to extrahepatic portal vein obstruction have long been described in
      literature under different names by various authors. Most of the times these
      changes are asymptomatic and discovered on imaging, but can occasionally cause
      obstructive jaundice. There is no consensus on the appropriate nomenclature and
      definition of this entity. This article reviews the history of portal
      hypertensive biliopathy and the Indian Association for the Study of Liver Working
      Party consensus definition and nomenclature for it. 

PMID- 25755590
TI  - Biliary tract anatomy and its relationship with venous drainage.
AB  - Portal cavernoma develops as a bunch of hepatopetal collaterals in response to
      portomesenteric venous obstruction and induces morphological changes in the
      biliary ducts, referred to as portal cavernoma cholangiopathy. This article
      briefly reviews the available literature on the vascular supply of the biliary
      tract in the light of biliary changes induced by portal cavernoma. Literature
      pertaining to venous drainage of the biliary tract is scanty whereas more
      attention was focused on the arterial supply probably because of its significant
      surgical implications in liver transplantation and development of ischemic
      changes and strictures in the bile duct due to vasculobiliary injuries. Since the
      general pattern of arterial supply and venous drainage of the bile ducts is quite
      similar, the arterial supply of the biliary tract is also reviewed. Fine branches
      from the posterior superior pancreaticoduodenal, retroportal, gastroduodenal,
      hepatic and cystic arteries form two plexuses to supply the bile ducts. The
      paracholedochal plexus, as right and left marginal arteries, run along the
      margins of the bile duct and the reticular epicholedochal plexus lie on the
      surface. The retropancreatic, hilar and intrahepatic parts of biliary tract has
      copious supply, but the supraduodenal bile duct has the poorest vascularization
      and hence susceptible to ischemic changes. Two venous plexuses drain the biliary
      tract. A fine reticular epicholedochal venous plexus on the wall of the bile duct
      drains into the paracholedochal venous plexus (also called as marginal veins or
      parabiliary venous system) which in turn is connected to the posterior superior
      pancreaticoduodenal vein, gastrocolic trunk, right gastric vein, superior
      mesenteric vein inferiorly and intrahepatic portal vein branches superiorly.
      These pericholedochal venous plexuses constitute the porto-portal collaterals and
      dilate in portomesenteric venous obstruction forming the portal cavernoma. 

PMID- 25755591
TI  - Portal cavernoma cholangiopathy: consensus statement of a working party of the
      Indian national association for study of the liver.
AB  - Portal cavernoma cholangiopathy (PCC) is defined as abnormalities in the
      extrahepatic biliary system including the cystic duct and gallbladder with or
      without abnormalities in the 1st and 2nd generation biliary ducts in a patient
      with portal cavernoma. Presence of a portal cavernoma, typical cholangiographic
      changes on endoscopic or magnetic resonance cholangiography and the absence of
      other causes of these biliary changes like bile duct injury, primary sclerosing
      cholangitis, cholangiocarcinoma etc are mandatory to arrive a diagnosis.
      Compression by porto-portal collateral veins involving the paracholedochal and
      epicholedochal venous plexuses and cholecystic veins and ischemic insult due to
      deficient portal blood supply or prolonged compression by collaterals bring about
      biliary changes. While the former are reversible after porto-systemic shunt
      surgery, the latter are not. Majority of the patients with PCC are asymptomatic
      and approximately 21% are symptomatic. Symptoms in PCC could be in the form of
      long standing jaundice due to chronic cholestasis, or biliary pain with or
      without cholangitis due to biliary stones. Endoscopic retrograde cholangiography
      has no diagnostic role because it is invasive and is associated with risk of
      complications, hence it is reserved for therapeutic procedures. Magnetic
      resonance cholangiography and portovenography is a noninvasive and comprehensive
      imaging technique, and is the modality of choice for mapping of the biliary and
      vascular abnormalities in these patients. PCC is a progressive condition and
      symptoms develop late in the course of portal hypertension only in patients with
      severe or advanced changes of cholangiopathy. Asymptomatic patients with PCC do
      not require any treatment. Treatment of symptomatic PCC can be approached in a
      phased manner, coping first with biliary clearance by nasobiliary or biliary
      stent placement for acute cholangitis and endoscopic biliary sphincterotomy for
      biliary stone removal; second, with portal decompression by creating
      portosystemic shunt; and third, with persistent biliary obstruction by performing
      second-stage biliary drainage surgery such as hepaticojejunostomy or
      choledochoduodenostomy. Patients with symptomatic PCC have good prognosis after
      successful endoscopic biliary drainage and after successful shunt surgery. 

PMID- 25755593
TI  - Portal cavernoma cholangiopathy-clinical characteristics.
AB  - Because of the presence of portal cavernoma, paracholedochal and pericholedochal
      varices, portal cavernoma cholangiopathy (PCC) has become an entity unique to
      patients with extrahepatic portal venous obstruction (EHPVO). Majority of
      patients with these abnormalities are asymptomatic and are incidentally detected
      to have the presence of biliary abnormalities on cholangiography. Minority of
      patients present with symptoms of chronic cholestasis with or without biliary
      pain or acute cholangitis related most often to the presence of biliary
      strictures or stones. Other than the age of the patient and duration of EHPVO,
      presence of gall stones and common bile duct stones are other risk factors for
      the causation of symptoms in patients with PCC. This review summarizes the
      clinical characteristics of asymptomatic and symptomatic patients with PCC giving
      details of the prevalence of symptoms, their risk factors and overall burden of
      symptomatic PCC. 

PMID- 25755592
TI  - Pathogenesis of Portal Cavernoma Cholangiopathy: Is it Compression by Collaterals
      or Ischemic Injury to Bile Ducts During Portal Vein Thrombosis?
AB  - The pathogenesis of portal cavernoma cholangiopathy (PCC) is important as it can
      impact the choice of treatment modalities. PCC consists of a reversible
      component, which resolves by decompression of collaterals as well as a fixed
      component, which persists despite the decompression of collaterals. The
      reversible component is due to compression by large collaterals located adjacent
      to the bile duct as well as possibly intracholedochal varices. The fixed
      component is likely to be due to ischemia at the time of portal vein thrombosis,
      local ischemia by compression as well as encasement by a solid tumor-like
      cavernoma comprising of fibrous hilar mass containing multiple tiny collateral
      veins rather than markedly enlarged portal collaterals. Although cholangiographic
      abnormalities in portal hypertension are common, the prevalence of symptomatic
      PCC is low. This is likely to be related to the cause of portal hypertension, the
      duration of portal hypertension and possibly the pattern of occlusion of the
      splenoportal axis. There may possibly be higher prevalence of symptomatic PCC in
      extension of the thrombosis to the splenomesentric veins. 

PMID- 25755594
TI  - Endoscopic retrograde cholangiography in portal cavernoma cholangiopathy -
      results from different studies and proposal for uniform terminology.
AB  - Portal cavernoma cholangiopathy (PCC) refers to a constellation of secondary
      changes in the biliary tree in patients with chronic portal vein (PV) thrombosis
      and portal cavernoma formation. These findings of PCC are seen in the extra
      hepatic bile duct(s), with or without involvement of the 1st or 2nd degree intra
      hepatic bile ducts. Of all patients with chronic PV thrombosis, cholangiographic
      features of PCC are found in 80%-100%. The biliary changes are symptomatic in a
      smaller proportion of 5%-38% patients. Choledocholithiasis and hepatolithiasis
      occur in 5%-20%, independent of the occurrence of cholelithiasis. We review the
      published literature on cholangiographic description of PCC. We also propose
      standardized nomenclature for the cholangiographic findings, namely: extrinsic
      impressions/indentations, shallow impressions, irregular ductal contour,
      stricture (s), upstream dilatation, filling defects, bile duct angulation, and
      ectasia. 

PMID- 25755595
TI  - Imaging of portal cavernoma cholangiopathy.
AB  - Portal cavernoma cholangiopathy (PCC) refers to the biliary changes which occur
      in the setting of extrahepatic portal vein obstruction and secondary portal
      cavernoma formation. The main radiological findings include the vascular changes
      in the form of portosystemic collaterals and biliary changes in the form of
      extrinsic impressions and strictures. Till date, conventional cholangiography has
      been the gold standard for the diagnosis of PCC. However, it is an invasive
      procedure and is associated with complications. At present there is a transition
      towards non-invasive modalities like ultrasound (US), computed tomography (CT)
      and magnetic resonance imaging (MRI). The recent advances in these modalities
      provide an excellent delineation of both the vascular and the biliary changes non
      invasively in a short time. The findings of PCC using these newer modalities are
      not so well described in literature. The findings of PCC also overlap with
      malignant conditions of biliary tract such as cholangiocarcinoma and compression
      of biliary tract by malignant adenopathies. In this article we describe the
      vascular and biliary changes associated with PCC on US, CT and MRI. We also
      describe the imaging findings using each modality along with their advantages and
      disadvantages. 

PMID- 25755596
TI  - Portal cavernoma cholangiopathy: an endoscopic ultrasound based imaging approach.
AB  - In patients with portal cavernoma cholangiopathy (PCC), appearance and location
      of collateral channels depends on extent and location of occlusive thrombus in
      the porto-mesenteric venous system. If the porto-mesenteric venous system is
      occluded near the formation of portal vein, blood tends to flow through
      collateral channels that form varices in and around the common bile duct. Though
      endoscopic ultrasound (EUS) is considered the investigative modality of choice
      for evaluating common bile duct obstruction, its role in evaluating collateral
      pathways in and around the common bile duct is poorly defined. This article
      reviews the anatomy, genesis and appearance of these collateral pathways in PCC.
      EUS identifies different layers of the common bile duct (CBD) wall and, in PCC,
      where varices are in close contact with or part of these different layers, can
      establish the relationship between them. Thus, EUS appears to be the
      investigation of choice for tracing the origin and course of collaterals in PCC.
      Careful study of varices in the common bile duct wall prior to ERCP for bile duct
      stones or biliary strictures may help to plan the procedure and to manage
      anticipated complications such as hemobilia. 

PMID- 25755597
TI  - Natural history of portal cavernoma cholangiopathy.
AB  - The natural history of portal cavernoma cholangiopathy (PCC) is poorly defined
      and poorly understood. It develops early after acute portal vein thrombosis (PVT)
      if there is failure of recanalization. In PCC, the likelihood of progression of
      biliary abnormalities after 1 year is extremely low. The natural history of PCC
      is conveniently divided into asymptomatic and symptomatic stages. The majority of
      patients with PCC are asymptomatic and are detected incidentally on imaging.
      Limited data suggest that asymptomatic PCC is static or only slowly progressive
      in the initial stages. However, most workers agree that, overall, PCC is a slowly
      progressive disease. Symptomatic PCC represents a late stage in its natural
      history. Finding strictures with dilatation at cholangiography is associated with
      a higher risk of developing symptoms of PCC. Onset of symptoms is often
      precipitated by the development of biliary sludge or calculi and treating calculi
      usually relieves symptoms for prolonged periods of time. Clinical presentations
      include biliary pain, obstructive jaundice, acute cholangitis, acute
      cholecystitis, or other presentations of gallstone disease. Progressive liver
      dysfunction and secondary biliary cirrhosis can develop in a minority of
      patients. 

PMID- 25755598
TI  - Endoscopic management of portal cavernoma cholangiopathy: practice, principles
      and strategy.
AB  - Portal cavernoma cholangiopathy (PCC) is the presence of typical cholangiographic
      changes in patients with a portal cavernoma due to chronic portal vein
      thrombosis, in the absence of other biliary tract diseases. Probably due to
      biliary stasis related to the cavernoma, there is a high incidence of biliary
      sludge and calculi in PCC, which trigger symptoms that resolve with appropriate
      interventions. Persistent and troublesome symptoms are usually due to biliary
      stenoses or strictures, which may occur with or without biliary calculi and may
      be short or long, solitary or multifocal, extrahepatic or intrahepatic.
      Experience with endoscopic interventions in PCC over the last twenty years has
      shown that it is the procedure of choice for bile duct calculi. Plastic stenting
      with repeated, timely, stent exchanges is the first line intervention for
      jaundice or cholangitis due to biliary strictures. If biliary obstruction does
      not resolve, portosystemic shunt surgery (PSS) or transjugular intrahepatic
      portosystemic stent shunt (TIPS) is performed to decompress the portal cavernoma.
      However, for patients with non-shuntable veins or blocked shunts, repeated
      plastic stent exchanges are the only option though there are reports of the use
      of biliary self-expandable metal stents in this situation. If symptomatic biliary
      obstruction persists after successful PSS or TIPS, second stage biliary surgery
      may be necessary. Recent experience suggests that treating biliary strictures in
      PCC on the lines of postoperative benign biliary strictures with balloon
      dilatation and repeated exchanges of plastic stent bundles may be effective
      therapy. Endoscopic management appears to be associated with an increased
      frequency of hemobilia, which usually responds to standard management. Recurrent
      cholangitis with formation of sludge and concretions may be a problem with
      repeated stent exchanges, especially if patient compliance is poor. In
      conclusion, the current understanding is that symptomatic PCC is best managed
      jointly by the endoscopist and surgeon with sequential interventions designed
      initially to establish and maintain biliary drainage, then to decompress the
      portal cavernoma and, finally, if required, second stage biliary surgery or
      endotherapy for biliary strictures. Endoscopic therapy occupies a central role in
      management before, during and after surgical therapy. Paradigms of endoscopic
      therapy continue to evolve as knowledge of pathogenesis and natural history
      improves and newer approaches and techniques are applied. 

PMID- 25755599
TI  - Surgical management of portal cavernoma cholangiopathy.
AB  - The majority of patients with portal cavernoma cholangiopathy (PCC) are
      asymptomatic, however some (5-38%) present with obstructive jaundice,
      cholangitis, or even biliary pain due to bile duct stones which form as a result
      of stasis. Most patients with extrahepatic portal venous obstruction (EHPVO)
      present with variceal bleeding and hypersplenism and these are the usual
      indications for surgery. Those who present with PCC may also need decompression
      of their portosystemic system to reverse the biliary obstruction. It is important
      to realize that though endoscopic drainage has been proposed as a non-surgical
      approach to the management of PCC it is successful in only certain specific
      situations like those with bile duct calculi, cholangitis, etc. A small
      proportion of such patients will continue to have biliary obstruction and these
      patients are thought to have a mechanical ischemic stricture. These patients will
      require a second stage procedure in the form of a bilioenteric bypass to reverse
      the symptoms related to PCC. In the absence of a shuntable vein splenectomy and
      devascularization may resolve the PCC in a subset of patients by decreasing the
      portal pressure. 

PMID- 25755600
TI  - Liver transplantation for portal cavernoma cholangiopathy.
AB  - Portal cavernoma cholangiopathy (PCC) is a difficult clinical problem, where the
      portal cavernoma is both the cause of biliary obstruction and the obstacle to its
      safe surgical treatment. The available endoscopic and surgical treatment is
      successful in majority and further intervention is seldom required since the
      native liver is normal. PCC is not an accepted indication for liver
      transplantation as only a small proportion of patients will fail both endoscopic
      and surgical treatment and progressive liver failure is rarely seen. Secondary
      biliary cirrhosis as a result of long standing biliary obstruction is an accepted
      indication however establishing a portal inflow in these patients is often
      difficult and challenging. The deceased donor liver transplantation would always
      be preferable over living donor liver transplantation as PCC is usually a non
      emergency transplant and the graft can have portal blood inflow through a conduit
      to even a small segment of patent portal venous system or even to a cavernoma
      vessel. 

PMID- 25755601
TI  - Role of local ablative therapy for hepatocellular carcinoma.
AB  - Percutaneous local ablation (PLA) techniques are currently considered as the best
      treatment option for patients with early-stage hepatocellular carcinoma (HCC) who
      are not candidates for surgical resection. They are safe, minimally invasive,
      efficacious and cost-effective. Radiofrequency ablation (RFA) is considered as
      the first line treatment in some centers, though most of the guidelines recommend
      it for small HCCs, where surgical resection is not feasible. In developing
      countries percutaneous ethanol injection (PEI) and percutaneous acetic acid
      injection (PAI) may be used instead of RFA. For large HCCs, advances in electrode
      designs and newer techniques of ablation, including microwave ablation, are
      increasingly been used. Combination treatment modalities have shown promising
      results as compared to single modality for large tumors. The selection of the
      most appropriate modality depends on the size, number of lesions, the liver
      function status, patient's financial resources, availability of a particular
      technique and the expertise available. 

PMID- 25755603
TI  - Role of external beam radiation therapy in management of hepatocellular
      carcinoma.
AB  - Diagnosis at advanced disease stage and early vascular invasion are the bane of
      majority of patients with hepatocellular carcinoma (HCC) in India. The currently
      standardized curative and palliative treatment modalities [surgery, ablative
      techniques, trans-catheter chemotherapy, systemic chemotherapy] are suboptimal
      for a significant proportion of disease stages. Interest in radiotherapy for
      hepatocellular carcinoma has seen a resurgence with revolutionary improvements in
      targeting radiation doses safely. Encouraging results have been reported with a
      host of radiation techniques from conformal radiotherapy, stereotactic whole body
      radiation therapy to charged particle based therapies. The dissemination of this
      knowledge has been slow across other specialties involved in care of patients
      with HCC. However the increasing availability of radiotherapy services predicts a
      hopeful future for wider evaluation of radiotherapy in HCC. 

PMID- 25755602
TI  - Role of Transcatheter Intra-arterial Therapies for Hepatocellular Carcinoma.
AB  - Transcatheter intra-arterial therapies play a vital role in treatment of HCC due
      to the unique tumor vasculature. Evolution of techniques and newer efficacious
      modalities of tumor destruction have made these techniques popular. Various types
      of intra-arterial therapeutic options are currently available. These constitute:
      bland embolization, trans-arterial chemotherapy, trans-arterial chemo
      embolization with or without drug-eluting beads and trans-arterial radio
      embolization, which are elaborated in this review. 

PMID- 25755604
TI  - Treatment Response Evaluation and Follow-up in Hepatocellular Carcinoma.
AB  - Hepatocellular carcinoma (HCC) is one of the major causes of morbidity, mortality
      and healthcare expenditure in patients with chronic liver disease. The management
      of HCC is evolving because of recently introduced novel therapeutic approaches.
      Optimal outcome requires an early and accurate assessment of tumor response to
      therapy. Current imaging modalities, such as computed tomography (CT) and
      magnetic resonance (MR) imaging; provide reliable and reproducible anatomical
      data in order to demonstrate tumor burden changes. However, in the setting of
      novel targeted therapies and liver directed treatments, simple tumor anatomical
      changes can be less informative and usually appear later than biological changes.
      There has been a growing interest to monitor the therapeutic response, at an
      early phase of treatment, by measuring tumor viability and/or perfusion.
      Therefore the importance of tumor viability assessment is increasingly being
      recognized. The tumor viability measurement guidelines have recently been amended
      to include the measurement of only the longest diameter of the enhancing tumors
      to formally amend RECIST to modified RECIST (mRECIST). Viable tumor should be
      defined as uptake of contrast agent in the arterial phase. In this review, we
      discuss criteria of response evaluation in HCC and further follow-up of patients
      receiving curative and palliative treatment. 

PMID- 25755606
TI  - Current practices in management of hepatocellular carcinoma in India: results of
      an online survey.
AB  - BACKGROUND: Prior to INASL guidelines, there were no Indian guidelines for
      management of hepatocellular carcinoma (HCC) in India. The guidelines given by
      other societies like AASLD, EASL etc are not uniform and not tailored for Indian
      patients. Hence management practices for HCC in India largely depended on
      physicians' individual preferences. This survey aimed to study current practices
      in management of HCC in India. METHODS: An online survey was conducted from the
      platform of a survey portal (www.surveymonkey.com), from December 2012 to April
      2013. Invitation to participate in the survey was sent to 1383 doctors of India
      who were expected to be involved in management of patients of HCC. The survey was
      of 10 min duration and consisted of questions on how the respondents diagnosed
      and managed patients of HCC. RESULTS: Three hundred and seventy-seven doctors
      answered the survey questions (72% gastroenterologists, 95% working in India).
      The important points which emerged from the survey are following: (i) The
      incidence of HCC is increasing in India; (ii) The most common etiologic agent is
      Hepatitis B responsible for 43% cases; (iii) Only 14% patients present in early
      stage when curative treatment is possible (BCLC-A); (iv) 90% of these respondents
      screen for HCC when they first evaluate a cirrhotic patient; (v) While following
      a patient of cirrhosis most respondents screen for HCC by ultrasound and AFP at
      every 6 months to 1 year; and (vi) Most (82%) respondents follow some
      international guideline for staging and treatment of HCC. The respondents also
      suggested that there is a need for spreading awareness about HCC in public as
      well as in medical fraternity, and there is a need for a national registry of
      HCC. CONCLUSIONS: This is the first survey on management practices on HCC. With
      the publication of the INASL guidelines on HCC, the diagnosis and treatment of
      HCC will be more uniform and protocol based. Further such surveys should be
      carried out at periodic interval to track increasing awareness and better
      management practices for HCC in India.

PMID- 25755605
TI  - Role of supportive care for terminal stage hepatocellular carcinoma.
AB  - Patients with end stage or terminal HCC are those presenting with tumors leading
      to a very poor Performance Status (ECOG 3-4) or Child-Pugh C patients with tumors
      beyond the transplantation threshold. Among HCC patients, 15-20% present with end
      stage or terminal stage HCC. Their median survival is less than 3-4 months. The
      management of end stage or terminal HCC is only symptomatic and no definitive
      tumor directed treatment is indicated. Patients with end stage or terminal HCC
      should receive palliative support including management of pain, nutrition and
      psychological support. In general, they should not be considered for
      participating in clinical trials. This review focuses on palliative care of
      terminal stage HCC. 

PMID- 25755607
TI  - Epidemiology of hepatocellular carcinoma in India.
AB  - Indian data on epidemiology of HCC is not available. Cancer is not a reportable
      disease in India and the cancer registries in India are mostly urban. National
      cancer registry program of the Indian Council of Medical Research (ICMR) has been
      recently expanded to include 21 population based and 6 hospital based cancer
      registries. The last published registry data by ICMR available in the cancer
      registry website (www.ncrpindia.org) was in 2008 which provides information on
      various cancers from 2006 to 2008. The other source of information was the report
      published by International Agency for Research on Cancer (WHO). According to
      these available data the age adjusted incidence rate of hepatocellular carcinoma
      (HCC) in India for men ranges from 0.7 to 7.5 and for women 0.2 to 2.2 per
      100,000 population per year. The male:female ratio for HCC in India is 4:1. The
      age of presentation varies from 40 to 70 years. According to a study conducted by
      verbal autopsy in 1.1 million homes representing the whole country, the age
      standardized mortality rate for HCC in India for men is 6.8/100,000 and for women
      is 5.1/100,000. According to another study the incidence of HCC in cirrhotics in
      India is 1.6% per year. The unpublished data from various tertiary care centers
      suggest that the incidence of HCC is increasing in India. There is a need for a
      multi-centric HCC registry under the aegis of INASL. 

PMID- 25755609
TI  - Risk factors for hepatocellular carcinoma in India.
AB  - Hepatocellular carcinoma (HCC) is an important cause of death all over the world,
      more so in Asia and Africa. The representative data on epidemiology of HCC in
      India is very scanty and cancer is not a reportable disease in India and the
      cancer registries in India are mostly urban. 45 million people who are suffering
      from chronic Hepatitis B virus (HBV) infection and approximately 15 million
      people who are afflicted with chronic Hepatitis C virus (HCV) infection in India.
      HBV and HCV infection is considered an important etiologic factor in HCC.
      Positive association between HCC and consumption of alcohol where alcohol
      contribute as a cofactor for hepatotoxins and hepatitis viruses. Aflatoxin
      contamination in the diets, Hepatitis B virus infection and liver cirrhosis in
      Andhra Pradesh, India and direct chronic exposure to aflatoxins was shown to
      cause liver cirrhosis. Cirrhosis of liver of any cause lead to develop about 70%
      90% of HCC. Aflatoxin interact synergistically with Hepatitis B virus
      (HBV)/Hepatitis C virus (HCV) infection which increase the risk of HCC. HBV
      infection, HBV infection with Aflatoxin exposure, viral infection and alcohol
      consumption leading to overt cirrhosis of the liver, alcohol consumption leading
      to cirrhosis of the liver with viral infection are the predominant risk factor
      for the development of HCC. HCV and alcohol are also associated with HCC in
      India. Indians develop diabetes at younger age, Asians have strong genetic
      susceptibility for type II diabetes. Diabetes mellitus is identified as a risk
      factor for HCC. Prevention of viral infection by universal vaccination against
      hepatitis virus, HCC surveillance program, preventing alcoholic liver diseases,
      fungal contamination of grains and ground crops to prevent basically Aflatoxin
      exposure are important measures to prevent liver diseases and HCC among those at
      risk. 

PMID- 25755610
TI  - Role of surveillance in prevention of hepatocellular carcinoma.
AB  - Hepatocellular carcinoma is a common malignancy and one of the important public
      health problems in India. The surveillance of hepatocellular carcinoma (HCC) is
      an established approach to detect early cancers in patients with defined risks.
      However, there are still controversies and issues to be addressed regarding the
      optimal surveillance methods and interval. The current level of awareness among
      physicians in India about surveillance is low and the need and most cost
      effective surveillance strategy in developing country like ours is unclear. This
      article has tried to discuss these issues in their appropriate perspective. To
      address this complicated issue, a multicenter randomized prospective study
      however may be required. 

PMID- 25755612
TI  - Nodule in Liver: Investigations, Differential Diagnosis and Follow-up.
AB  - Conventional ultrasonogram of the abdomen being noninvasive, inexpensive and
      ubiquitously available is the first imaging modality that raises suspicion of HCC
      in a patient with chronic liver disease with or without cirrhosis. The lesions in
      liver particularly nodule are being recognized with increased frequency with the
      wide spread use of ultrasonogram as the initial investigation and computerized
      tomography and magnetic resonance imaging subsequently. Any nodule in a cirrhotic
      liver should be considered as hepatocellular carcinoma until otherwise proved.
      This approach certainly is helpful in diagnosing HCC at its earliest possible
      stage to offer meaningful curative measures be it transplant, resection or
      ablative therapy. After a nodule is detected on ultrasonogram the next imaging
      modality can be a contrast enhanced study (dynamic CT scan or an MRI) to see if
      are present or not. Two vital clues for diagnosis of HCC by contrast enhanced
      imaging are presence of arterial hypervascularity and washout which are
      considered as "classical imaging features". This sequence of events of arterial
      uptake followed by washout is highly specific for diagnosis of HCC by imaging. If
      the features are typical showing classical imaging features (i.e hypervascular in
      the arterial phase with washout in portal venous or delayed phase) the lesion
      should be treated as HCC biopsy is not necessary. Nodular lesions showing an
      atypical imaging pattern, such as iso- or hypovascular in the arterial phase or
      arterial hypervascularity alone without portal venous washout, should undergo
      further examinations with another contrast enhanced imaging. Biopsy is advisable
      for those lesions which do not show classical features on the imaging. 

PMID- 25755611
TI  - Surveillance for hepatocellular carcinoma.
AB  - Hepatocellular carcinoma (HCC) is a dreaded complication of cirrhosis as it is
      the commonest cause of mortality in these patients. The last few years have seen
      a dramatic improvement in the management of this tumor as nearly 50-70% of
      selected patients with early HCC survive for a median period of up to 5 years
      after liver transplantation, resection or local ablation. Surveillance has been
      found to be an effective tool to detect early tumors and expand the applicability
      of these curative treatment options. Semiannual ultrasonogram is recommended for
      surveillance by the American, European and Asia Pacific liver societies and is
      the standard of care in many countries. There is increasing evidence that this
      practice improves survival too. Since the only way to improve the outlook of HCC
      is its diagnosis prior to commencement of symptoms, providing surveillance
      becomes a major responsibility of physicians caring for patients with chronic
      liver disease. This review attempts to discuss the population at risk of HCC,
      modalities and frequency of surveillance tests, cost effectiveness and also the
      logistics of its delivery in the Indian context. 

PMID- 25755613
TI  - Radiological features of hepatocellular carcinoma.
AB  - Present article is a review of radiological features of hepatocellular carcinoma
      on various imaging modalities. With the advancement in imaging techniques, biopsy
      is rarely needed for diagnosis of hepatocellular carcinoma (HCC), unlike other
      malignancies. Imaging is useful not only for diagnosis but also for surveillance,
      therapy and assessing response to treatment. The classical and the atypical
      radiological features of HCC have been described. 

PMID- 25755608
TI  - The Indian National Association for Study of the Liver (INASL) Consensus on
      Prevention, Diagnosis and Management of Hepatocellular Carcinoma in India: The
      Puri Recommendations.
AB  - Hepatocellular carcinoma (HCC) is one of the major causes of morbidity, mortality
      and healthcare expenditure in patients with chronic liver disease. There are no
      consensus guidelines on diagnosis and management of HCC in India. The Indian
      National Association for Study of the Liver (INASL) set up a Task-Force on HCC in
      2011, with a mandate to develop consensus guidelines for diagnosis and management
      of HCC, relevant to disease patterns and clinical practices in India. The Task
      Force first identified various contentious issues on various aspects of HCC and
      these issues were allotted to individual members of the Task-Force who reviewed
      them in detail. The Task-Force used the Oxford Center for Evidence Based Medicine
      Levels of Evidence of 2009 for developing an evidence-based approach. A 2-day
      round table discussion was held on 9th and 10th February, 2013 at Puri, Odisha,
      to discuss, debate, and finalize the consensus statements. The members of the
      Task-Force reviewed and discussed the existing literature at this meeting and
      formulated the INASL consensus statements for each of the issues. We present here
      the INASL consensus guidelines (The Puri Recommendations) on prevention,
      diagnosis and management of HCC in India. 

PMID- 25755614
TI  - Tissue diagnosis of hepatocellular carcinoma.
AB  - The current American Association for the Study of Liver Diseases (AASLD)
      guideline provides strategies for achieving the diagnosis of hepatocellular
      carcinoma (HCC) based on the size of liver nodules seen on surveillance imaging.
      For lesions less than 1 cm in size, follow-up surveillance imaging is
      recommended. Lesions larger than 2 cm require typical radiological hallmark on
      dynamic imaging. Lesions of 1-2 cm in size require typical imaging features
      including intense uptake of contrast during arterial phases followed by decreased
      enhancement during portal venous phases on at least 2 imaging modalities. In
      cases of atypical radiological features of the suspected lesion, tissue diagnosis
      either by fine needle aspiration or biopsy should be obtained. Although fine
      needle aspiration could give a smaller risk of seeding than biopsy, biopsy has
      been preferred over cytology. Percutaneous biopsy of HCC carries a potential risk
      of tumor seeding along the needle tract. However the risk is low and there is no
      clear evidence of post transplant recurrence due to needle tract seeding.
      Histopathologic assessment can differentiate between premalignant lesions such as
      dysplastic nodules and early HCC. Atypical variants of HCC can be recognized
      morphologically which may have associated prognostic value. 

PMID- 25755615
TI  - Staging of hepatocellular carcinoma.
AB  - Hepatocellular carcinoma (HCC) is different from other malignancies because the
      prognosis in HCC is not only dependent upon the tumor stage but also on the liver
      function impairment due to accompanying cirrhosis liver. Various other staging
      systems used in HCC include the European systems [French staging system,
      Barcelona Clinic Liver Cancer (BCLC) staging system and the cancer of the liver
      Italian program (CLIP)] and Asian systems [Okuda staging system, Japan integrated
      Staging (JIS), Tokyo score and Chinese University Prognostic Index (CUPI)]. Out
      of all the staging systems used in HCC, Barcelona Clinic Liver Cancer (BCLC)
      staging system is probably the best because it takes in to account the tumor
      status (defined by tumor size and number, presence of vascular invasion and
      extrahepatic spread), liver function (defined either by the Child-Pugh's class)
      and general health status of the patient (defined by the ECOG classification and
      the presence of symptoms). Since most of the extrahepatic spread in HCC occurs to
      lymph nodes, lungs and bones, the assessment can be done with either PET/CT or a
      combination of CT (Chest and abdomen) and a bone scan. This article describes the
      various staging systems used in HCC, guides choosing a staging system
      particularly in the Indian context and the assessment of extra-hepatic spread in
      HCC. 

PMID- 25755616
TI  - Treatment algorithms for managing hepatocellular carcinoma.
AB  - Early diagnosis and aggressive therapy improves outcome in hepatocellular
      carcinoma (HCC). Several potentially curative as well as palliative treatment
      options are available for patients. The choice of therapy is influenced by
      factors such as extent of tumor and severity of underlying liver dysfunction as
      well as availability of resources and of expertise. A systematic, algorithmic
      approach would ensure optimal therapy for each patient and is likely to improve
      outcomes. Even after receiving therapy for HCC, patients remain at risk for
      recurrent HCC as well as progression of underlying cirrhosis. Proper assessment
      and monitoring is needed for the underlying liver disease, which may progress to
      liver failure and have a major impact on long-term survival. Comprehensive care
      for patients with cirrhosis includes interventions such as antiviral therapy for
      HBV and HCV, abstention from alcohol, management of fatty liver disease,
      endoscopic surveillance and treatment for complications of portal hypertension
      and, if indicated, immunization against HAV and HBV. An algorithmic approach is
      useful for choosing the most appropriate treatment option for the individual
      patient from among the various options that are available. The general consensus
      is that the BCLC system should be preferred for staging HCC as it is useful in
      predicting outcomes and planning treatment. The BCLC system classifies patients
      with HCC into five categories: very early, early, intermediate, advanced, and
      terminal. It incorporates data on tumor status (number and size of nodules,
      vascular invasion, extra-hepatic spread), liver function (CTP status, presence of
      portal hypertension) and overall health status (constitutional symptoms, cancer
      symptoms, performance status). Treatment allocation according to sub-class of
      patients is a merit of the BCLC system; a few limitations have been noted,
      particularly with respect to patients with BCLC stage B and C disease. The
      treatment algorithm as per BCLC system is summarized in this review. 

PMID- 25755617
TI  - Resection for hepatocellular carcinoma.
AB  - Hepatocellular Carcinoma (HCC) continues to present major challenges in
      management, which is further complicated by the presence of associated chronic
      liver disease. Key issues in surgical resection of HCC include the site, size,
      and number of lesions, the severity of the chronic liver disease, and the size of
      the functional liver remnant. De novo HCC in the absence of chronic liver disease
      can be treated by major liver resection with little risk of postoperative liver
      failure. Liver resection can also be used a bridge to liver transplantation as it
      affords the possibility of determining the pathologic grade of the tumortumor and
      its invasiveness, and thereby the prognosis. This review summarizes the current
      treatment approaches to surgical resection for HCC. 

PMID- 25755618
TI  - Role of liver transplantation for hepatocellular carcinoma.
AB  - This review evaluates the available evidence to establish the role of liver
      transplantation in the management of hepatocellular carcinoma in India. Most
      liver transplants in India are living donor transplants due to the paucity of
      brain dead organ donors. There is sufficient evidence to permit allocation of
      organs to patients with tumors within the Milan criteria. If the waiting list
      time is more than 6 months, a down-staging locoregional treatment modality such a
      trans-arterial chemoembolization, radiofrequency ablation, resection or
      percutaneous ethanol injection may be used to prevent disease progression.
      Allocating scarce livers to patients with more advanced tumors may not be
      justifiable. However, living donor liver transplantation may be offered to
      medically fit patients with hepatocellular carcinoma with cirrhosis, offering a
      guarded prognosis to patients beyond the Milan or UCSF criteria. Vascular
      invasion and extra-hepatic disease should be absolute contraindications to liver
      transplantation. 

PMID- 25755619
TI  - Unintended Effects of an Intervention Supporting Mexican-Heritage Youth:
      Decreased Parent Heavy Drinking.
AB  - OBJECTIVE: To assess the impact of a parenting intervention, Familias: Preparando
      la Nueva Generacion (FPNG), intended to support children, on parents heavy
      drinking. We hypothesized that parent participants of FPNG would reduce their
      heavy drinking at 1-year follow-up. METHODS: Parents (N = 281) of middle school
      children from a large, low-income metropolitan area in the Southwest United
      States participated in a randomized control trial over 2 years. RESULTS: A
      logistic regression analysis using the maximum likelihood test determined that at
      Wave 3, parents receiving FPNG reduced heavy drinking behaviors compared to
      parents in the youth-only condition (odds ratio = .86, p < .05). CONCLUSIONS:
      Participating in the parenting program can effectively curb heavy drinking
      behaviors in parents-an important mechanism through which one may expect changes
      in youth risk behavior. The practice, policy, and research implications of these
      unintended findings are promising to the overall effectiveness of a parenting
      intervention for Mexican-heritage families.

PMID- 25755621
TI  - A new millipede of the family Ammodesmidae found in central Africa (Diplopoda,
      Polydesmida).
AB  - The first species of the small Afrotropical family Ammodesmidae discovered in
      central Africa (Democratic Republic of the Congo) belongs to the genus Ammodesmus
      Cook, 1896, which was hitherto known only from two species in western Africa. A
      key is given to incorporate Ammodesmuscongoensis sp. n., a species also showing
      an evident sex dimorphism: ? densely hirsute, ? with much longer and sparser
      tergal setae. 

PMID- 25755622
TI  - Revised concept of the fossil genus Oviparosiphum Shaposhnikov, 1979 with the
      description of a new genus (Hemiptera, Sternorrhyncha, Aphidomorpha).
AB  - This paper presents a revision of the aphid genus Oviparosiphum, which is known
      from the Cretaceous period. Redescriptions of two species: Oviparosiphumjakovlevi
      Shaposhnikov, 1979 and Oviparosiphumbaissense Shaposhnikov & Wegierek, 1989 are
      made, and an updated diagnosis of this genus is provided. Oviparosiphumbaissense
      is the type species of a newly described genus Archeoviparosiphum gen. n. Five
      other species of Oviparosiphum are also transferred to the new genus. The basis
      for their separation from Oviparosiphum is the structure of the siphunculi and
      ovipositor. A key is provided to the genera of Oviparosiphidae. 

PMID- 25755620
TI  - Promoting convergence: the Phi spiral in abduction of mouse corneal behaviors.
AB  - Why do mouse corneal epithelial cells display spiraling patterns? We want to
      provide an explanation for this phenomenon by applying an idealized problem
      solving process. Specifically, we applied complementary line-fitting methods to
      measure transgenic epithelial reporter expression arrangements displayed on three
      mature, live enucleated globes to clarify the problem. Two prominent logarithmic
      curves were discovered, one of which displayed the phi ratio, an indicator of the
      optimal configuration in phyllotactic systems. We then utilized two different
      computational approaches to expose our current understanding of the behavior. In
      one procedure, which involved an isotropic mechanics-based finite element method,
      we successfully produced logarithmic spiral curves of maximum shear strain based
      pathlines but computed dimensions displayed pitch angles of 35 degrees  (phi
      spiral is ~17 degrees ), which was altered when we fitted the model with
      published measurements of coarse collagen orientations. We then used model-based
      reasoning in context of Peircean abduction to select a working hypothesis. Our
      work serves as a concise example of applying a scientific habit of mind and
      illustrates nuances of executing a common method to doing integrative science.

PMID- 25755623
TI  - Palearctic elements in the old world tropics: a taxonomic revision of the ant
      genus Temnothorax Mayr (Hymenoptera, Formicidae) for the Afrotropical
      biogeographical region.
AB  - Four new Afrotropical species of the ant genus Temnothorax are described and
      illustrated, all from Kenya. Based upon high resemblance to taxa known from the
      North African and Iberian territories of the Mediterranean region, these new
      tropical elements are placed into known Palaearctic species complexes.
      Specifically, Temnothoraxbrevidentis sp. n., Temnothoraxmpala sp. n. and
      Temnothoraxrufus sp. n. are placed in the laurae species group, and
      Temnothoraxsolidinodus sp. n. is placed in the angustulus species group. Two
      already known Temnothorax species from the region, Temnothoraxcenatus (Bolton,
      1982) and Temnothoraxmegalops (Hamann & Klemm, 1967), are also placed into the
      laurae species group based on the high number of shared morphological characters.
      Diagnoses for the African representatives of laurae and angustulus species groups
      of the Afrotropical biogeographical region are provided. A key to workers of the
      six Temnothorax species known to occur in the Afrotropical biogeographical region
      is provided, as well as diagnoses of morphologically similar myrmicine genera. 

PMID- 25755624
TI  - The paleoenvironments of azhdarchid pterosaurs localities in the Late Cretaceous
      of Kazakhstan.
AB  - Five pterosaur localities are currently known from the Late Cretaceous in the
      northeastern Aral Sea region of Kazakhstan. Of these, one is Turonian-Coniacian
      in age, the Zhirkindek Formation (Tyulkili), and four are Santonian in age, all
      from the early Campanian Bostobe Formation (Baibishe, Akkurgan, Buroinak, and
      Shakh Shakh). All so far collected and identifiable Late Cretaceous pterosaur
      bones from Kazakhstan likely belong to Azhdarchidae: Azhdarcho sp. (Tyulkili);
      Aralazhdarchobostobensis (Shakh Shakh); and Samrukianessovi (Akkurgan). These
      latter two taxa, both from the Bostobe Formation might be synonyms. Azhdarcho sp.
      from the Zhirkindek Formation lived in a tropical-to-subtropical relatively humid
      climate on the shore of an estuarine basin connected to the Turgai Sea. Known
      fossils were collected in association with brackish-water bivalves and so the
      overall paleoenvironment of this pterosaur was likely an estuarine marsh as
      indicated by the dominance of conifers and low relative counts of ferns and
      angiosperms. Aralazhdarchobostobensis, from the Bostobe Formation, lived on a
      coastal fluvial plain along the Turgai Sea. This paleoenvironment was either
      floodplain (Akkurgan, Buroinak, and Shakh Shakh) or estuarine (Baibishe). In the
      Santonian - early Campanian, shallow waters near this coastal plain were sites
      for the intensive accumulation of phosphates under upwelling conditions caused by
      strong winds from the ancient Asian landmass. These winds also caused significant
      aridization of the climate during this time. We speculate that pterosaurs may
      have been attracted to this area by the abundant resources in the bio-productive
      estuaries and nearshore upwelling waters. 

PMID- 25755625
TI  - Two new species of Zospeum Bourguignat, 1856 from the Basque-Cantabrian
      Mountains, Northern Spain (Eupulmonata, Ellobioidea, Carychiidae).
AB  - Two new species of the genus Zospeum Bourguignat, 1856 are described from caves
      in the Sierra de Aitzgorri (Gipuzkoa) and the Sierra Salvada (Burgos) in Northern
      Spain. The taxa Zospeumvasconicum sp. n. and Zospeumzaldivarae sp. n. have
      recently, without a formal name, been included in a molecular study of worldwide
      members of the Carychiidae. In the present paper, the shell morphology and
      variation of these species is described and illustrated. 

PMID- 25755626
TI  - A revision of the Nearctic species of Liancalus Loew (Diptera, Dolichopodidae).
AB  - The genus Liancalus Loew is revised for the Nearctic Region. Seven species are
      documented from this region including two new species: Liancalusgenualis Loew,
      Liancalushydrophilus Aldrich, Liancaluslimbatus Van Duzee, Liancaluspterodactyl
      sp. n., Liancalusquerulus Osten Sacken, Liancalussimilis Aldrich, and
      Liancalussonorus sp. n. Lectotypes are designated for the following species:
      Liancalusgenualis, Liancalushydrophilus, Liancalusquerulus, and Liancalussimilis.
      The species are illustrated, a key to males and females is provided, and their
      distributions mapped. Adults of Liancalus are some of the largest species of
      Dolichopodidae and commonly occur on waterfalls and vertical seeps. 

PMID- 25755627
TI  - Halechiniscidae (Heterotardigrada, Arthrotardigrada) of Oura Bay, Okinawajima,
      Ryukyu Islands, with descriptions of three new species.
AB  - Marine tardigrades of the family Halechiniscidae (Heterotardigrada:
      Arthrotardigrada) are reported from Oura Bay, Okinawajima, one of the Ryukyu
      Islands, Japan, including Dipodarctus sp., Florarctuswunai sp. n.,
      Halechiniscuschurakaagii sp. n., Halechiniscusyanakaagii sp. n. and Styraconyx
      sp. The attributes distinguishing Florarctuswunai sp. n. from its congeners is a
      combination of two characters, the smooth dorsal cuticle and two small
      projections of the caudal alae caestus. Halechiniscuschurakaagii sp. n. is
      differentiated from its congeners by the combination of two characters, the
      robust cephalic cirrophores and the scapular processes with flat oval tips, while
      Halechiniscusyanakaagii sp. n. can be identified by the laterally protruded
      arched double processes with acute tips situated dorsally at the level of leg I.
      A list of marine tardigrades reported from the Ryukyu Islands is provided. 

PMID- 25755628
TI  - Tromboelastography: variability and relation to conventional coagulation test in
      non-bleeding intensive care unit patients.
AB  - BACKGROUND: Intensive care unit (ICU) patients usually have abnormal biochemical
      and hematological laboratory test results as a consequence of organ dysfunction
      and underlying disease. Thromboelastography (TEG(r)) is a point-of-care
      laboratory analysis that gives an overview of several aspects of the coagulation
      process. In order to be able to perform a clinical interpretation of abnormal
      TEG(r) results the expected values from non-bleeding ICU patients should be
      known. The aim of this study is to report the normal variability observed in non
      bleeding, non-transfused ICU patients. METHODS: Adult ICU patients without
      bleeding in the last 24 hours, who had not received blood products within the
      last 24 hours, with no hematological diseases and no anticoagulation therapeutic
      treatment were included. Standard clinical chemistry tests, coagulation tests and
      TEG(r) were obtained. All results were reported in relation to standard reference
      values. TEG(r) values were compared with routine coagulation measurement using
      Spearman correlations. RESULTS: We observed that the normal variability observed
      in non-bleeding, non-transfused ICU patients in this study included abnormally
      high TEG(r) values for maximum amplitude (MA) (73%). None of the patients showed
      MA results corresponding to hypocoagulability. Other coagulation tests were also
      changed with elevated D-Dimer, fibrinogen and APTT values, and a low ATIII value.
      CONCLUSION: In unselected ICU patients without bleeding or known factors that
      influence coagulation, a TEG(r) value of MA is often elevated suggesting
      hypercoagulability. This finding should be considered when interpreting TEG(r)
      observations obtained in ICU patients.

PMID- 25755629
TI  - Diabetes Associated Metabolomic Perturbations in NOD Mice.
AB  - Non-obese diabetic (NOD) mice are a widely-used model oftype1 diabetes (T1D).
      However, not all animals develop overt diabetes. This study examined the
      circulating metabolomic profiles of NOD mice progressing or not progressing to
      T1D. Total beta-cell mass was quantified in the intact pancreas using transgenic
      NOD mice expressinggreen fluorescent protein under the control of mouse insulin I
      promoter.While both progressor and non-progressor animals displayed lymphocyte
      infiltration and endoplasmic reticulum stress in the pancreas tissue;overt T1D
      did not develop until animals lost ~70% of the total beta-cell mass.Gas
      chromatography time of flight mass spectrometry (GC-TOF) was used to measure >470
      circulating metabolites in male and female progressor and non-progressor animals
      (n=76) across a wide range of ages (neonates to >40-wk).Statistical and
      multivariate analyses were used to identify age and sex independent metabolic
      markers which best differentiated progressor and non-progressor animals'
      metabolic profiles. Key T1D-associated perturbations were related with: (1)
      increased plasma glucose and reduced 1,5-anhydroglucitol markers of glycemic
      control; (2) increased allantoin, gluconic acid and nitric oxide-derived
      saccharic acid markers of oxidative stress; (3) reduced lysine, an insulin
      secretagogue; (4) increased branched-chain amino acids, isoleucine and valine;
      (5) reduced unsaturated fatty acids including arachidonic acid; and
      (6)perturbations in urea cycle intermediates suggesting increased arginine
      dependent NO synthesis. Together these findings highlight the strength of the
      unique approach of comparing progressor and non-progressor NOD mice to identify
      metabolic perturbations involved in T1D progression.

PMID- 25755630
TI  - Progesterone mediates brain functional connectivity changes during the menstrual
      cycle-a pilot resting state MRI study.
AB  - The growing interest in intrinsic brain organization has sparked various
      innovative approaches to generating comprehensive connectivity-based maps of the
      human brain. Prior reports point to a sexual dimorphism of the structural and
      functional human connectome. However, it is uncertain whether subtle changes in
      sex hormones, as occur during the monthly menstrual cycle, substantially impact
      the functional architecture of the female brain. Here, we performed eigenvector
      centrality (EC) mapping in 32 longitudinal resting state fMRI scans of a single
      healthy subject without oral contraceptive use, across four menstrual cycles, and
      assessed estrogen and progesterone levels. To investigate associations between
      cycle-dependent hormones and brain connectivity, we performed correlation
      analyses between the EC maps and the respective hormone levels. On the whole
      brain level, we found a significant positive correlation between progesterone and
      EC in the bilateral dorsolateral prefrontal cortex (DLPFC) and bilateral
      sensorimotor cortex. In a secondary region-of-interest analysis, we detected a
      progesterone-modulated increase in functional connectivity of both bilateral
      DLPFC and bilateral sensorimotor cortex with the hippocampus. Our results suggest
      that the menstrual cycle substantially impacts intrinsic functional connectivity,
      particularly in brain areas associated with contextual memory-regulation, such as
      the hippocampus. These findings are the first to link the subtle hormonal
      fluctuations that occur during the menstrual cycle, to significant changes in
      regional functional connectivity in the hippocampus in a longitudinal design,
      given the limitation of data acquisition in a single subject. Our study
      demonstrates the feasibility of such a longitudinal Resting-state functional
      Magnetic Resonance Imaging (rs-fMRI) design and illustrates a means of creating a
      personalized map of the human brain by integrating potential mediators of brain
      states, such as menstrual cycle phase. 

PMID- 25755631
TI  - Neural correlates underlying naloxone-induced amelioration of sexual behavior
      deterioration due to an alarm pheromone.
AB  - Sexual behavior is suppressed by various types of stressors. We previously
      demonstrated that an alarm pheromone released by stressed male Wistar rats is a
      stressor to other rats, increases the number of mounts needed for ejaculation,
      and decreases the hit rate (described as the number of intromissions/sum of the
      mounts and intromissions). This deterioration in sexual behavior was ameliorated
      by pretreatment with the opioid receptor antagonist naloxone. However, the neural
      mechanism underlying this remains to be elucidated. Here, we examined Fos
      expression in 31 brain regions of pheromone-exposed rats and naloxone-pretreated
      pheromone-exposed rats 60 min after 10 intromissions. As previously reported, the
      alarm pheromone increased the number of mounts and decreased the hit rate. In
      addition, Fos expression was increases in the anterior medial division (BNSTam),
      anterior lateral division (BNSTal) and posterior division (BNSTp) of the bed
      nucleus of the stria terminalis, parvocellular part of the paraventricular
      nucleus of the hypothalamus, arcuate nucleus, dorsolateral and ventrolateral
      periaqueductal gray, and nucleus paragigantocellularis (nPGi). Fos expression was
      decreased in the magnocellular part of the paraventricular nucleus of the
      hypothalamus. Pretreatment with naloxone blocked the pheromone-induced changes in
      Fos expression in the magnocellular part of the paraventricular nucleus of the
      hypothalamus, ventrolateral periaqueductal gray, and nPGi. Based on these
      results, we hypothesize that the alarm pheromone deteriorated sexual behavior by
      activating the ventrolateral periaqueductal gray-nucleus paragigantocellularis
      cluster and suppressing the magnocellular part of the paraventricular nucleus of
      the hypothalamus (PVN) via the opioidergic pathway. 

PMID- 25755632
TI  - Plasticity-related microRNA and their potential contribution to the maintenance
      of long-term potentiation.
AB  - Long-term potentiation (LTP) is a form of synaptic plasticity that is an
      excellent model for the molecular mechanisms that underlie memory. LTP, like
      memory, is persistent, and both are widely believed to be maintained by a
      coordinated genomic response. Recently, a novel class of non-coding RNA,
      microRNA, has been implicated in the regulation of LTP. MicroRNA negatively
      regulate protein synthesis by binding to specific messenger RNA response
      elements. The aim of this review is to summarize experimental evidence for the
      proposal that microRNA play a major role in the regulation of LTP. We discuss a
      growing body of research which indicates that specific microRNA regulate synaptic
      proteins relevant to LTP maintenance, as well as studies that have reported
      differential expression of microRNA in response to LTP induction. We conclude
      that microRNA are ideally suited to contribute to the regulation of LTP-related
      gene expression; microRNA are pleiotropic, synaptically located, tightly
      regulated, and function in response to synaptic activity. The potential impact of
      microRNA on LTP maintenance as regulators of gene expression is enormous. 

PMID- 25755633
TI  - Truncated tau deregulates synaptic markers in rat model for human tauopathy.
AB  - Synaptic failure and neurofibrillary degeneration are two major neuropathological
      substrates of cognitive dysfunction in Alzheimer's disease (AD). Only a few
      studies have demonstrated a direct relationship between these two AD hallmarks.
      To investigate tau mediated synaptic injury we used rat model of tauopathy that
      develops extensive neurofibrillary pathology in the cortex. Using fractionation
      of cortical synapses, we identified an increase in endogenous rat tau isoforms in
      presynaptic compartment, and their mis-sorting to the postsynaptic density (PSD).
      Truncated transgenic tau was distributed in both compartments exhibiting specific
      phospho-pattern that was characteristic for each synaptic compartment. In the
      presynaptic compartment, truncated tau was associated with impairment of dynamic
      stability of microtubules which could be responsible for reduction of synaptic
      vesicles. In the PSD, truncated tau lowered the levels of neurofilaments.
      Truncated tau also significantly decreased the synaptic levels of Abeta40 but not
      Abeta42. These data show that truncated tau differentially deregulates synaptic
      proteome in pre- and postsynaptic compartments. Importantly, we show that
      alteration of Abeta can arise downstream of truncated tau pathology. 

PMID- 25755634
TI  - Generation of a Retinoblastoma (Rb)1-inducible dominant-negative (DN) mouse
      model.
AB  - Retinoblastoma 1 (Rb1) is an essential gene regulating cellular proliferation,
      differentiation, and homeostasis. To exert these functions, Rb1 is recruited and
      physically interacts with a growing variety of signaling pathways. While Rb1 does
      not appear to be ubiquitously expressed, its expression has been confirmed in a
      variety of hematopoietic and neuronal-derived cells, including the inner ear hair
      cells (HCs). Studies in transgenic mice demonstrate that complete germline or
      conditional Rb1 deletion leads to abnormal cell proliferation, followed by
      massive apoptosis; making it difficult to fully address Rb1's biochemical
      activities. To overcome these limitations, we developed a tetracycline-inducible
      TetO-CB-myc6-Rb1 (CBRb) mouse model to achieve transient and inducible dominant
      negative (DN) inhibition of the endogenous RB1 protein. Our strategy involved
      fusing the Rb1 gene to the lysosomal protease pre-procathepsin B (CB), thus
      allowing for further routing of the DN-CBRb fusion protein and its interacting
      complexes for proteolytic degradation. Moreover, reversibility of the system is
      achieved upon suppression of doxycycline (Dox) administration. Preliminary
      characterization of DN-CBRb mice bred to a ubiquitous rtTA mouse line
      demonstrated a significant inhibition of the endogenous RB1 protein in the inner
      ear and in a number of other organs where RB1 is expressed. Examination of the
      postnatal (P) DN-CBRb mice inner ear at P10 and P28 showed the presence of
      supernumerary inner HCs (IHCs) in the lower turns of the cochleae, which
      corresponds to the described expression domain of the endogenous Rb1 gene.
      Selective and reversible suppression of gene expression is both an experimental
      tool for defining function and a potential means to medical therapy. Given the
      limitations associated with Rb1-null mice lethality, this model provides a
      valuable resource for understanding RB1 activity, relative contribution to HC
      regeneration and its potential therapeutic application. 

PMID- 25755635
TI  - Microglia in action: how aging and injury can change the brain's guardians.
AB  - Neuroinflammation, the inflammatory response in the central nervous system (CNS),
      is a major determinant of neuronal function and survival during aging and disease
      progression. Microglia, as the resident tissue-macrophages of the brain, provide
      constant support to surrounding neurons in healthy brain. Upon any stress signal
      (such as trauma, ischemia, inflammation) they are one of the first cells to
      react. Local and/or peripheral signals determine microglia stress response, which
      can vary within a continuum of states from beneficial to detrimental for neuronal
      survival, and can be shaped by aging and previous insults. In this review, we
      discuss the roles of microglia upon an ischemic or traumatic injury, and give our
      perspective how aging may contribute to microglia behavior in the injured brain.
      We speculate that a deeper understanding of specific microglia identities will
      pave the way to develop more potent therapeutics to treat the diseases of aging
      brain. 

PMID- 25755636
TI  - Novel subcellular localization for alpha-synuclein: possible functional
      consequences.
AB  - alpha-synuclein (alpha-syn) is one of the genes that when mutated or
      overexpressed causes Parkinson's Disease (PD). Initially, it was described as a
      synaptic terminal protein and later was found to be localized at mitochondria.
      Mitochondria-associated membranes (MAM) have emerged as a central endoplasmic
      reticulum (ER) subcellular compartments where key functions of the cell occur.
      These domains, enriched in cholesterol and anionic phospholipids, are where
      calcium homeostasis, lipid transfer, and cholesterol metabolism are regulated.
      Some proteins, related to mitochondrial dynamics and function, are also localized
      to this area. Several neurodegenerative diseases have shown alterations in MAM
      functions and resident proteins, including Charcot Marie-Tooth and Alzheimer's
      disease (AD). We have recently reported that MAM function is downregulated in
      cell and mouse models of PD expressing pathogenic mutations of alpha-syn. This
      review focuses on the possible role of alpha-syn in these cellular domains and
      the early pathogenic features of PD that could be explained by alpha-syn-MAM
      disturbances. 

PMID- 25755638
TI  - Stimulus information stored in lasting active and hidden network states is
      destroyed by network bursts.
AB  - In both humans and animals brief synchronizing bursts of epileptiform activity
      known as interictal epileptiform discharges (IEDs) can, even in the absence of
      overt seizures, cause transient cognitive impairments (TCI) that include problems
      with perception or short-term memory. While no evidence from single units is
      available, it has been assumed that IEDs destroy information represented in
      neuronal networks. Cultured neuronal networks are a model for generic cortical
      microcircuits, and their spontaneous activity is characterized by the presence of
      synchronized network bursts (SNBs), which share a number of properties with IEDs,
      including the high degree of synchronization and their spontaneous occurrence in
      the absence of an external stimulus. As a model approach to understanding the
      processes underlying IEDs, optogenetic stimulation and multielectrode array (MEA)
      recordings of cultured neuronal networks were used to study whether stimulus
      information represented in these networks survives SNBs. When such networks are
      optically stimulated they encode and maintain stimulus information for as long as
      one second. Experiments involved recording the network response to a single
      stimulus and trials where two different stimuli were presented sequentially, akin
      to a paired pulse trial. We broke the sequential stimulus trials into encoding,
      delay and readout phases and found that regardless of which phase the SNB occurs,
      stimulus-specific information was impaired. SNBs were observed to increase the
      mean network firing rate, but this did not translate monotonically into increases
      in network entropy. It was found that the more excitable a network, the more
      stereotyped its response was during a network burst. These measurements speak to
      whether SNBs are capable of transmitting information in addition to blocking it.
      These results are consistent with previous reports and provide baseline
      predictions concerning the neural mechanisms by which IEDs might cause TCI. 

PMID- 25755637
TI  - Filling gaps in visual motion for target capture.
AB  - A remarkable challenge our brain must face constantly when interacting with the
      environment is represented by ambiguous and, at times, even missing sensory
      information. This is particularly compelling for visual information, being the
      main sensory system we rely upon to gather cues about the external world. It is
      not uncommon, for example, that objects catching our attention may disappear
      temporarily from view, occluded by visual obstacles in the foreground.
      Nevertheless, we are often able to keep our gaze on them throughout the occlusion
      or even catch them on the fly in the face of the transient lack of visual motion
      information. This implies that the brain can fill the gaps of missing sensory
      information by extrapolating the object motion through the occlusion. In recent
      years, much experimental evidence has been accumulated that both perceptual and
      motor processes exploit visual motion extrapolation mechanisms. Moreover,
      neurophysiological and neuroimaging studies have identified brain regions
      potentially involved in the predictive representation of the occluded target
      motion. Within this framework, ocular pursuit and manual interceptive behavior
      have proven to be useful experimental models for investigating visual
      extrapolation mechanisms. Studies in these fields have pointed out that visual
      motion extrapolation processes depend on manifold information related to short
      term memory representations of the target motion before the occlusion, as well as
      to longer term representations derived from previous experience with the
      environment. We will review recent oculomotor and manual interception literature
      to provide up-to-date views on the neurophysiological underpinnings of visual
      motion extrapolation. 

PMID- 25755639
TI  - Digit ratio (2D:4D) and altruism: evidence from a large, multi-ethnic sample.
AB  - We look at the links between the Digit Ratio-the ratio of the length of the index
      finger to the length of the ring finger-for both right and left hands, and giving
      in a Dictator Game. Unlike previous studies with exclusively Caucasian subjects,
      we consider a large, ethnically diverse sample. Our main results are as follows.
      First, for Caucasian subjects we estimate a significant positive regression
      coefficient for the right hand digit ratio and a significant negative coefficient
      for its squared measure. These results replicate the findings of Branas-Garza et
      al. (2013), who also observe an inverted U-shaped relationship for Caucasian
      subjects. Second, we are not able to find any significant association of the
      right hand digit ratio with giving in the Dictator Game for the other main ethnic
      groups in our sample, nor in the pooled sample. Third, we find no significant
      association between giving in the Dictator Game and the left hand digit ratio. 

PMID- 25755640
TI  - The lemon illusion: seeing curvature where there is none.
AB  - Curvature is a highly informative visual cue for shape perception and object
      recognition. We introduce a novel illusion-the Lemon Illusion-in which subtle
      illusory curvature is perceived along contour regions that are devoid of physical
      curvature. We offer several perceptual demonstrations and observations that lead
      us to conclude that the Lemon Illusion is an instance of a more general illusory
      curvature phenomenon, one in which the presence of contour curvature
      discontinuities lead to the erroneous extension of perceived curvature. We
      propose that this erroneous extension of perceived curvature results from the
      interaction of neural mechanisms that operate on spatially local contour
      curvature signals with higher-tier mechanisms that serve to establish more global
      representations of object shape. Our observations suggest that the Lemon Illusion
      stems from discontinuous curvature transitions between rectilinear and curved
      contour segments. However, the presence of curvature discontinuities is not
      sufficient to produce the Lemon Illusion, and the minimal conditions necessary to
      elicit this subtle and insidious illusion are difficult to pin down. 

PMID- 25755641
TI  - Repeated cycles of chronic intermittent ethanol exposure increases basal
      glutamate in the nucleus accumbens of mice without affecting glutamate transport.
AB  - Repeated cycles of chronic intermittent ethanol (CIE) exposure increase voluntary
      consumption of ethanol in mice. Previous work has shown that extracellular
      glutamate in the nucleus accumbens (NAc) is significantly elevated in ethanol
      dependent mice and that pharmacologically manipulating glutamate concentrations
      in the NAc will alter ethanol drinking, indicating that glutamate homeostasis
      plays a crucial role in ethanol drinking in this model. The present studies were
      designed to measure extracellular glutamate at a time point in which mice would
      ordinarily be allowed voluntary access to ethanol in the CIE model and,
      additionally, to measure glutamate transport capacity in the NAc at the same time
      point. Extracellular glutamate was measured using quantitative microdialysis
      procedures. Glutamate transport capacity was measured under Na(+)-dependent and
      Na(+)-independent conditions to determine whether the function of excitatory
      amino acid transporters (also known as system XAG) or of system Xc (-) (glial
      cysteine-glutamate exchanger) was influenced by CIE exposure. The results of the
      quantitative microdialysis experiment confirm increased extracellular glutamate
      (approximately twofold) in the NAc of CIE exposed mice (i.e., ethanol-dependent)
      compared to non-dependent mice in the NAc, consistent with earlier work. However,
      the increase in extracellular glutamate was not due to altered transporter
      function in the NAc of ethanol-dependent mice, because neither Na(+)-dependent
      nor Na(+)-independent glutamate transport was significantly altered by CIE
      exposure. These findings point to the possibility that hyperexcitability of
      cortical-striatal pathways underlies the increases in extracellular glutamate
      found in the ethanol-dependent mice. 

PMID- 25755642
TI  - Homer2 deletion alters dendritic spine morphology but not alcohol-associated
      adaptations in GluN2B-containing N-methyl-D-aspartate receptors in the nucleus
      accumbens.
AB  - Repeated exposure to ethanol followed by withdrawal leads to alterations in
      glutamatergic signaling and impaired synaptic plasticity in the nucleus accumbens
      (NAc) in both clinical and preclinical models of ethanol exposure. Homer2 is a
      member of a family of postsynaptic density (PSD) scaffolding proteins that
      functions in part to cluster N-methyl-D-aspartate (NMDA) signaling complexes in
      the PSD, and has been shown to be critically important for plasticity in multiple
      models of drug and alcohol abuse. Here we used Homer2 knockout (KO) mice and a
      chronic intermittent intraperitoneal (IP) ethanol injection model to investigate
      a potential role for the protein in ethanol-induced adaptations in dendritic
      spine morphology and PSD protein expression. While deletion of Homer2 was
      associated with increased density of long spines on medium spiny neurons of the
      NAc core of saline treated mice, ethanol exposure had no effect on dendritic
      spine morphology in either wild-type (WT) or Homer2 KO mice. Western blot
      analysis of tissue samples from the NAc enriched for PSD proteins revealed a main
      effect of ethanol treatment on the expression of GluN2B, but there was no effect
      of genotype or treatment on the expression other glutamate receptor subunits or
      PSD95. These data indicate that the global deletion of Homer2 leads to aberrant
      regulation of dendritic spine morphology in the NAc core that is associated with
      an increased density of long, thin spines. Unexpectedly, intermittent IP ethanol
      did not affect spine morphology in either WT or KO mice. Together these data
      implicate Homer2 in the formation of long, thin spines and further supports its
      role in neuronal structure. 

PMID- 25755643
TI  - Potential effects of intrinsic heart pacemaker cell mechanisms on dysrhythmic
      cardiac action potential firing.
AB  - The heart's regular electrical activity is initiated by specialized cardiac
      pacemaker cells residing in the sinoatrial node. The rate and rhythm of
      spontaneous action potential firing of sinoatrial node cells are regulated by
      stochastic mechanisms that determine the level of coupling of chemical to
      electrical clocks within cardiac pacemaker cells. This coupled-clock system is
      modulated by autonomic signaling from the brain via neurotransmitter release from
      the vagus and sympathetic nerves. Abnormalities in brain-heart clock connections
      or in any molecular clock activity within pacemaker cells lead to abnormalities
      in the beating rate and rhythm of the pacemaker tissue that initiates the cardiac
      impulse. Dysfunction of pacemaker tissue can lead to tachy-brady heart rate
      alternation or exit block that leads to long atrial pauses and increases
      susceptibility to other cardiac arrhythmia. Here we review evidence for the idea
      that disturbances in the intrinsic components of pacemaker cells may be
      implemented in arrhythmia induction in the heart. 

PMID- 25755644
TI  - Biomaterials and bioactive molecules to drive differentiation in striated muscle
      tissue engineering.

PMID- 25755646
TI  - Memory distortion for traumatic events: the role of mental imagery.

PMID- 25755645
TI  - Chronic subordinate colony housing paradigm: a mouse model to characterize the
      consequences of insufficient glucocorticoid signaling.
AB  - Chronic, in particular chronic psychosocial, stress is a burden of modern
      societies and known to be a risk factor for numerous somatic and affective
      disorders (in detail referenced below). However, based on the limited existence
      of appropriate, and clinically relevant, animal models for studying the effects
      of chronic stress, the detailed behavioral, physiological, neuronal, and
      immunological mechanisms linking stress and such disorders are insufficiently
      understood. To date, most chronic stress studies in animals employ intermittent
      exposure to the same (homotypic) or to different (heterotypic) stressors of
      varying duration and intensity. Such models are only of limited value, since they
      do not adequately reflect the chronic and continuous situation that humans
      typically experience. Furthermore, application of different physical or
      psychological stimuli renders comparisons to the mainly psychosocial stressors
      faced by humans, as well as between the different stress studies almost
      impossible. In contrast, rodent models of chronic psychosocial stress represent
      situations more akin to those faced by humans and consequently seem to hold more
      clinical relevance. Our laboratory has developed a model in which mice are
      exposed to social stress for 19 continuous days, namely the chronic subordinate
      colony housing (CSC) paradigm, to help bridge this gap. The main aim of the
      current review article is to provide a detailed summary of the behavioral,
      physiological, neuronal, and immunological consequences of the CSC paradigm, and
      wherever possible relate the findings to other stress models and to the human
      situation. 

PMID- 25755647
TI  - Pattern destabilization and emotional processing in cognitive therapy for
      personality disorders.
AB  - Clinical trials of treatments for personality disorders can provide a medium for
      studying the process of therapeutic change with particularly entrenched and self
      perpetuating systems and might reveal important principles of system transition.
      We examined the extent to which maladaptive personality patterns were
      destabilized in a trial of cognitive therapy personality disorders (CT-PD) and
      how destabilization was associated with emotional processing and treatment
      outcomes. Dynamic systems theory was used as a theoretical framework for studying
      change. METHOD: Participants were 27 patients diagnosed with Avoidant or
      Obsessive Compulsive Personality Disorder (AVPD or OCPD), who completed an open
      trial of CT-PD. Raters coded treatment sessions using a coding system that
      operationalizes emotional processing, as well as cognitive, affective,
      behavioral, and somatic components of pathological (negative) and more adaptive
      (positive) patterns of functioning. Pattern destabilization (dispersion) scores
      during the early phase of treatment (phase 1: session 1-10) and the schema
      focused phase (phase 2: session 11-34) were calculated using a program called
      GridWare. RESULTS: More pattern destabilization and emotional processing in the
      schema-focused phase of CT-PD predicted more improvement in personality disorder
      symptoms and positive pattern strength at the end of treatment, whereas these
      variables in phase 1 did not predict outcome. CONCLUSION: In addition to
      illustrating a quantitative method for studying destabilization and change of
      patterns of psychopathology, we present findings that are consistent with recent
      updates of emotional processing theory and with principles from dynamic systems
      theory.

PMID- 25755648
TI  - Improvement in Fatigue during Natalizumab Treatment is Linked to Improvement in
      Depression and Day-Time Sleepiness.
AB  - BACKGROUND: Fatigue is a frequent symptom in multiple sclerosis (MS) and often
      interrelated with depression and sleep disorders making symptomatic treatment
      decisions difficult. In the single-arm, observational phase IV TYNERGY study,
      relapsing-remitting MS patients showed a clinically meaningful decrease in
      fatigue over 1 year of treatment with natalizumab. OBJECTIVE: To evaluate whether
      fatigue improvement might be directly linked to improved depression and day-time
      sleepiness. METHODS: Patients were assessed regarding fatigue, depression, and
      day-time sleepiness. The relation between changes of the two latter symptoms and
      changes in fatigue was analyzed. RESULTS: After 1 year of natalizumab treatment,
      the majority of patients (>92%) remained stable or improved in total, motor, and
      cognitive fatigue. Proportion of patients without depression increased by 17%
      while proportions of mildly depressed patients or patients with potential major
      depression decreased by 5 and 12%, respectively. Proportion of patients
      classified as not being sleepy increased by 13% while proportions of sleepy and
      very sleepy patients decreased by 11 and 2%, respectively. Most importantly,
      improved depression and sleepiness were significantly related to improved
      fatigue. CONCLUSION: Our findings highlight the importance of patient-reported
      outcomes in identifying potential benefits of drug treatment beyond its well
      established effects on disease activity and disability progression.

PMID- 25755650
TI  - Podocytes ... What's Under Yours? (Podocytes and Foot Processes and How They
      Change in Nephropathy).
AB  - Most of the described structures of podocytes in health and disease have been
      inferred from light and electron microscopic studies of rodent models. The
      variation in filtration barrier features is measured on micrographs, the aim
      being statistical significance. This is the technical campaign waged against
      kidney disease but this approach can be misleading. The signaling cascades and
      connectivity of the podocyte and foot processes (FPs) are inferred from in vitro
      studies that at best blurr the reality of the in vivo state. This review will
      outline actin signaling connectivity and the key differences in the structural
      and functional domains squeezed into the FPs and the relationship of these
      domains to other parts of the podocyte. It covers the changes in podocytes during
      nephropathy concentrating on FP and finally proposes an alternative
      interpretation of FP ultrastructure derived from articles published over the last
      60 years. 

PMID- 25755651
TI  - Comparative genomics of Roseobacter clade bacteria isolated from the accessory
      nidamental gland of Euprymna scolopes.
AB  - The accessory nidamental gland (ANG) of the female Hawaiian bobtail squid,
      Euprymna scolopes, houses a consortium of bacteria including members of the
      Flavobacteriales, Rhizobiales, and Verrucomicrobia but is dominated by members of
      the Roseobacter clade (Rhodobacterales) within the Alphaproteobacteria. These
      bacteria are deposited into the jelly coat of the squid's eggs, however, the
      function of the ANG and its bacterial symbionts has yet to be elucidated. In
      order to gain insight into this consortium and its potential role in host
      reproduction, we cultured 12 Rhodobacterales isolates from ANGs of sexually
      mature female squid and sequenced their genomes with Illumina sequencing
      technology. For taxonomic analyses, the ribosomal proteins of 79 genomes
      representing both roseobacters and non-roseobacters along with a separate MLSA
      analysis of 33 housekeeping genes from Roseobacter organisms placed all 12
      isolates from the ANG within two groups of a single Roseobacter clade. Average
      nucelotide identity analysis suggests the ANG isolates represent three genera
      (Leisingera, Ruegeria, and Tateyamaria) comprised of seven putative species
      groups. All but one of the isolates contains a predicted Type VI secretion
      system, which has been shown to be important in secreting signaling and/or
      effector molecules in host-microbe associations and in bacteria-bacteria
      interactions. All sequenced genomes also show potential for secondary metabolite
      production, and are predicted to be involved with the production of acyl
      homoserine lactones (AHLs) and/or siderophores. An AHL bioassay confirmed AHL
      production in three tested isolates and from whole ANG homogenates. The dominant
      symbiont, Leisingera sp. ANG1, showed greater viability in iron-limiting
      conditions compared to other roseobacters, possibly due to higher levels of
      siderophore production. Future comparisons will try to elucidate novel metabolic
      pathways of the ANG symbionts to understand their putative role in host
      development. 

PMID- 25755649
TI  - Pitfalls in the neuroimaging of glioblastoma in the era of antiangiogenic and
      immuno/targeted therapy - detecting illusive disease, defining response.
AB  - Glioblastoma, the most common malignant primary brain tumor in adults is a
      devastating diagnosis with an average survival of 14-16 months using the current
      standard of care treatment. The determination of treatment response and clinical
      decision making is based on the accuracy of radiographic assessment.
      Notwithstanding, challenges exist in the neuroimaging evaluation of patients
      undergoing treatment for malignant glioma. Differentiating treatment response
      from tumor progression is problematic and currently combines long-term follow-up
      using standard magnetic resonance imaging (MRI), with clinical status and
      corticosteroid-dependency assessments. In the clinical trial setting, treatment
      with gene therapy, vaccines, immunotherapy, and targeted biologicals similarly
      produces MRI changes mimicking disease progression. A neuroimaging method to
      clearly distinguish between pseudoprogression and tumor progression has
      unfortunately not been found to date. With the incorporation of antiangiogenic
      therapies, a further pitfall in imaging interpretation is pseudoresponse. The
      Macdonald criteria that correlate tumor burden with contrast-enhanced imaging
      proved insufficient and misleading in the context of rapid blood-brain barrier
      normalization following antiangiogenic treatment that is not accompanied by
      expected survival benefit. Even improved criteria, such as the RANO criteria,
      which incorporate non-enhancing disease, clinical status, and need for
      corticosteroid use, fall short of definitively distinguishing tumor progression,
      pseudoresponse, and pseudoprogression. This review focuses on advanced imaging
      techniques including perfusion MRI, diffusion MRI, MR spectroscopy, and new
      positron emission tomography imaging tracers. The relevant image analysis
      algorithms and interpretation methods of these promising techniques are discussed
      in the context of determining response and progression during treatment of
      glioblastoma both in the standard of care and in clinical trial context. 

PMID- 25755652
TI  - Involvement of glycolysis/gluconeogenesis and signaling regulatory pathways in
      Saccharomyces cerevisiae biofilms during fermentation.
AB  - Compared to free (free-living) cells, biofilm cells show increased resistance and
      stability to high-pressure fermentation conditions, although the reasons
      underlying these phenomena remain unclear. Here, we investigated biofilm
      formation with immobilized Saccharomyces cerevisiae cells grown on fiber surfaces
      during the process of ethanol fermentation. The development of biofilm colonies
      was visualized by fluorescent labeling and confocal microscopy. RNA from yeast
      cells at three different biofilm development periods was extracted and sequenced
      by high-throughput sequencing. We quantitated gene expression differences between
      biofilm cells and free cells and found that 2098, 1556, and 927 genes were
      significantly differentially expressed, respectively. We also validated the
      expression of previously reported genes and identified novel genes and pathways
      under the control of this system. Statistical analysis revealed that biofilm
      genes show significant gene expression changes principally in the initial period
      of biofilm formation compared to later periods. Carbohydrate metabolism, amino
      acid metabolism, signal transduction, and oxidoreductase activity were needed for
      biofilm formation. In contrast to previous findings, we observed some
      differential expression performances of FLO family genes, indicating that cell
      aggregation in our immobilized fermentation system was possibly independent of
      flocculation. Cyclic AMP-protein kinase A and mitogen-activated protein kinase
      pathways regulated signal transduction pathways during yeast biofilm formation.
      We found that carbohydrate metabolism, especially glycolysis/gluconeogenesis,
      played a key role in the development of S. cerevisiae biofilms. This work
      provides an important dataset for future studies aimed at gaining insight into
      the regulatory mechanisms of immobilized cells in biofilms, as well as for
      optimizing bioprocessing applications with S. cerevisiae. 

PMID- 25755653
TI  - Shaping of the host cell by viral accessory proteins.

PMID- 25755655
TI  - Understanding the ontogeny of the immune system to promote immune-mediated health
      for life.

PMID- 25755656
TI  - Mechanosensitive control of plant growth: bearing the load, sensing, transducing,
      and responding.
AB  - As land plants grow and develop, they encounter complex mechanical challenges,
      especially from winds and turgor pressure. Mechanosensitive control over growth
      and morphogenesis is an adaptive trait, reducing the risks of breakage or
      explosion. This control has been mostly studied through experiments with
      artificial mechanical loads, often focusing on cellular or molecular
      mechanotransduction pathway. However, some important aspects of mechanosensing
      are often neglected. (i) What are the mechanical characteristics of different
      loads and how are loads distributed within different organs? (ii) What is the
      relevant mechanical stimulus in the cell? Is it stress, strain, or energy? (iii)
      How do mechanosensing cells signal to meristematic cells? Without answers to
      these questions we cannot make progress analyzing the mechanobiological effects
      of plant size, plant shape, tissue distribution and stiffness, or the magnitude
      of stimuli. This situation is rapidly changing however, as systems mechanobiology
      is being developed, using specific biomechanical and/or mechanobiological models.
      These models are instrumental in comparing loads and responses between
      experiments and make it possible to quantitatively test biological hypotheses
      describing the mechanotransduction networks. This review is designed for a
      general plant science audience and aims to help biologists master the models they
      need for mechanobiological studies. Analysis and modeling is broken down into
      four steps looking at how the structure bears the load, how the distributed load
      is sensed, how the mechanical signal is transduced, and then how the plant
      responds through growth. Throughout, two examples of adaptive responses are used
      to illustrate this approach: the thigmorphogenetic syndrome of plant shoots
      bending and the mechanosensitive control of shoot apical meristem (SAM)
      morphogenesis. Overall this should provide a generic understanding of systems
      mechanobiology at work. 

PMID- 25755654
TI  - Tertiary Lymphoid Structure-Associated B Cells are Key Players in Anti-Tumor
      Immunity.
AB  - It is now admitted that the immune system plays a major role in tumor control.
      Besides the existence of tumor-specific T cells and B cells, many studies have
      demonstrated that high numbers of tumor-infiltrating lymphocytes are associated
      with good clinical outcome. In addition, not only the density but also the
      organization of tumor-infiltrating immune cells has been shown to determine
      patient survival. Indeed, more and more studies describe the development within
      the tumor microenvironment of tertiary lymphoid structures (TLS), whose presence
      has a positive impact on tumor prognosis. TLS are transient ectopic lymphoid
      aggregates displaying the same organization and functionality as canonical
      secondary lymphoid organs, with T-cell-rich and B-cell-rich areas that are sites
      for the differentiation of effector and memory T cells and B cells. However,
      factors favoring the emergence of such structures within tumors still need to be
      fully characterized. In this review, we survey the state of the art of what is
      known about the general organization, induction, and functionality of TLS during
      chronic inflammation, and more especially in cancer, with a particular focus on
      the B-cell compartment. We detail the role played by TLS B cells in anti-tumor
      immunity, both as antigen-presenting cells and tumor antigen-specific antibody
      secreting cells, and raise the question of the capacity of chemotherapeutic and
      immunotherapeutic agents to induce the development of TLS within tumors. Finally,
      we explore how to take advantage of our knowledge on TLS B cells to develop new
      therapeutic tools. 

PMID- 25755657
TI  - MicroRNAs and drought responses in sugarcane.
AB  - There is a growing demand for renewable energy, and sugarcane is a promising
      bioenergy crop. In Brazil, the largest sugarcane producer in the world, sugarcane
      plantations are expanding into areas where severe droughts are common. Recent
      evidence has highlighted the role of miRNAs in regulating drought responses in
      several species, including sugarcane. This review summarizes the data from miRNA
      expression profiles observed in a wide array of experimental conditions using
      different sugarcane cultivars that differ in their tolerance to drought. We
      uncovered a complex regulation of sugarcane miRNAs in response to drought and
      discussed these data with the miRNA profiles observed in other plant species. The
      predicted miRNA targets revealed different transcription factors, proteins
      involved in tolerance to oxidative stress, cell modification, as well as hormone
      signaling. Some of these proteins might regulate sugarcane responses to drought,
      such as reduction of internode growth and shoot branching and increased leaf
      senescence. A better understanding on the regulatory network from miRNAs and
      their targets under drought stress has a great potential to contribute to
      sugarcane improvement, either as molecular markers as well as by using
      biotechnological approaches. 

PMID- 25755658
TI  - The Epl1 and Sm1 proteins from Trichoderma atroviride and Trichoderma virens
      differentially modulate systemic disease resistance against different life style
      pathogens in Solanum lycopersicum.
AB  - Fungi belonging to the genus Trichoderma, commonly found in soil or colonizing
      plant roots, exert beneficial effects on plants, including the promotion of
      growth and the induction of resistance to disease. T. virens and T. atroviride
      secrete the proteins Sm1 and Epl1, respectively, which elicit local and systemic
      disease resistance in plants. In this work, we show that these fungi promote
      growth in tomato (Solanum lycopersicum) plants. T. virens was more effective than
      T. atroviride in promoting biomass gain, and both fungi were capable of inducing
      systemic protection in tomato against Alternaria solani, Botrytis cinerea, and
      Pseudomonas syringae pv. tomato (Pst DC3000). Deletion (KO) of epl1 in T.
      atroviride resulted in diminished systemic protection against A. solani and B.
      cinerea, whereas the T. virens sm1 KO strain was less effective in protecting
      tomato against Pst DC3000 and B. cinerea. Importantly, overexpression (OE) of
      epl1 and sm1 led to an increase in disease resistance against all tested
      pathogens. Although the Trichoderma WT strains induced both systemic acquired
      resistance (SAR)- and induced systemic resistance (ISR)-related genes in tomato,
      inoculation of plants with OE and KO strains revealed that Epl1 and Sm1 play a
      minor role in the induction of these genes. However, we found that Epl1 and Sm1
      induce the expression of a peroxidase and an alpha-dioxygenase encoding genes,
      respectively, which could be important for tomato protection by Trichoderma spp.
      Altogether, these observations indicate that colonization by beneficial and/or
      infection by pathogenic microorganisms dictates many of the outcomes in plants,
      which are more complex than previously thought. 

PMID- 25755659
TI  - Current knowledge in lentil genomics and its application for crop improvement.
AB  - Most of the lentil growing countries face a certain set of abiotic and biotic
      stresses causing substantial reduction in crop growth, yield, and production.
      Until-to date, lentil breeders have used conventional plant breeding techniques
      of selection-recombination-selection cycle to develop improved cultivars.These
      techniques have been successful in mainstreaming some of the easy-to-manage
      monogenic traits. However, in case of complex quantitative traits, these
      conventional techniques are less precise. As most of the economic traits are
      complex, quantitative, and often influenced by environments and genotype
      environment interaction, the genetic improvement of these traits becomes
      difficult. Genomics assisted breeding is relatively powerful and fast approach to
      develop high yielding varieties more suitable to adverse environmental
      conditions. New tools such as molecular markers and bioinformatics are expected
      to generate new knowledge and improve our understanding on the genetics of
      complex traits. In the past, the limited availability of genomic resources in
      lentil could not allow breeders to employ these tools in mainstream breeding
      program.The recent application of the next generation sequencing and genotyping
      by sequencing technologies has facilitated to speed up the lentil genome
      sequencing project and large discovery of genome-wide single nucleotide
      polymorphism (SNP) markers. Currently, several linkage maps have been developed
      in lentil through the use of expressed sequenced tag (EST) derived simple
      sequence repeat (SSR) and SNP markers.These maps have emerged as useful genomic
      resources to identify quantitative trait loci imparting tolerance to biotic and
      abiotic stresses in lentil. In this review, the current knowledge on available
      genomic resources and its application in lentil breeding program are discussed. 

PMID- 25755660
TI  - Foliar application of microbial and plant based biostimulants increases growth
      and potassium uptake in almond (Prunus dulcis [Mill.] D. A. Webb).
AB  - The use of biostimulants has become a common practice in agriculture. However,
      there is little peer-reviewed research on this topic. In this study we tested,
      under controlled and replicated conditions, the effect of one biostimulant
      derived from seaweed extraction (Bio-1) and another biostimulant derived from
      microbial fermentation (Bio-2). This experiment utilized 2-years-old almond
      plants over two growing seasons in a randomized complete design with a full 2 * 4
      factorial structure with two soil potassium treatments (125 MUg g(-1) of K vs. 5
      MUg g(-1)) and four foliar treatments (No spray, Foliar-K, Bio-1, Bio-2).
      Rubidium was utilized as a surrogate for short-term potassium uptake and plant
      growth, nutrient concentration, and final plant biomass were evaluated. There was
      a substantial positive effect of both biostimulant treatments on total shoot leaf
      area, and significant increases in shoot length and biomass under adequate soil
      potassium supply with a positive effect of Bio-1 only under low K supply.
      Rubidium uptake was increased by Bio-1 application an effect that was greater
      under the low soil K treatment. Though significant beneficial effects of the
      biostimulants used on plant growth were observed, it is not possible to determine
      the mode of action of these materials. The results presented here illustrate the
      promise and complexity of research involving biostimulants. 

PMID- 25755661
TI  - B-GATA transcription factors - insights into their structure, regulation, and
      role in plant development.
AB  - GATA transcription factors are evolutionarily conserved transcriptional
      regulators that recognize promoter elements with a G-A-T-A core sequence. In
      comparison to animal genomes, the GATA transcription factor family in plants is
      comparatively large with approximately 30 members. Here, we review the current
      knowledge on B-GATAs, one of four GATA factor subfamilies from Arabidopsis
      thaliana. We show that B-GATAs can be subdivided based on structural features and
      their biological function into family members with a C-terminal LLM- (leucine
      leucine-methionine) domain or an N-terminal HAN- (HANABA TARANU) domain. The
      paralogous GNC (GATA, NITRATE-INDUCIBLE, CARBON-METABOLISM INVOLVED) and CGA1/GNL
      (CYTOKININ-INDUCED GATA1/GNC-LIKE) are introduced as LLM-domain containing B
      GATAs from Arabidopsis that control germination, greening, senescence, and
      flowering time downstream from several growth regulatory signals. Arabidopsis HAN
      and its monocot-specific paralogs from rice (NECK LEAF1), maize (TASSEL SHEATH1),
      and barley (THIRD OUTER GLUME) are HAN-domain-containing B-GATAs with a
      predominant role in embryo development and floral development. We also review
      GATA23, a regulator of lateral root initiation from Arabidopsis that is closely
      related to GNC and GNL but has a degenerate LLM-domain that is seemingly specific
      for the Brassicaceae family. The Brassicaceae-specific GATA23 and the monocot
      specific HAN-domain GATAs provide evidence that neofunctionalization of B-GATAs
      was used during plant evolution to expand the functional repertoire of these
      transcription factors. 

PMID- 25755662
TI  - Polyol specificity of recombinant Arabidopsis thaliana sorbitol dehydrogenase
      studied by enzyme kinetics and in silico modeling.
AB  - Polyols are enzymatically-produced plant compounds which can act as compatible
      solutes during periods of abiotic stress. Nicotinamide adenine dinucleotide(+)
      dependent SORBITOL DEHYDROGENASE (SDH, E. C. 1.1.1.14) from Arabidopsis thaliana
      L. sorbitol dehydrogenase (AtSDH) is capable of oxidizing several polyols
      including sorbitol, ribitol, and xylitol. In the present study, enzymatic assays
      using recombinant AtSDH demonstrated a higher specificity constant for xylitol
      compared to sorbitol and ribitol, all of which are C2 (S) and C4 (R) polyols.
      Enzyme activity was reduced by preincubation with ethylenediaminetetraacetic
      acid, indicating a requirement for zinc ions. In humans, it has been proposed
      that sorbitol becomes part of a pentahedric coordination sphere of the catalytic
      zinc during the reaction mechanism. In order to determine the validity of this
      pentahedric coordination model in a plant SDH, homology modeling, and Molecular
      Dynamics simulations of AtSDH ternary complexes with the three polyols were
      performed using crystal structures of human and Bemisia argentifolii (Genn.)
      (Hemiptera: Aleyrodidae) SDHs as scaffolds. The results indicate that the
      differences in interaction with structural water molecules correlate very well
      with the observed enzymatic parameters, validate the proposed pentahedric
      coordination of the catalytic zinc ion in a plant SDH, and provide an explanation
      for why AtSDH shows a preference for polyols with a chirality of C2 (S) and C4
      (R). 

PMID- 25755663
TI  - On reproduction in red algae: further research needed at the molecular level.
AB  - Multicellular red algae (Rhodophyta) have some of the most complex life cycles
      known in living organisms. Economically valuable seaweeds, such as phycocolloid
      producers, have a triphasic (gametophyte, carposporophyte, and tetrasporophyte)
      life cycle, not to mention the intricate alternation of generations in the edible
      "sushi-alga" nori. It is a well-known fact that reproductive processes are
      controlled by one or more abiotic factor(s), including day length, light quality,
      temperature, and nutrients. Likewise, endogenous chemical factors such as plant
      growth regulators have been reported to affect reproductive events in some red
      seaweeds. Still, in the genomic era and given the high throughput techniques at
      our disposal, our knowledge about the endogenous molecular machinery lags far
      behind that of higher plants. Any potential effective control of the reproductive
      process will entail revisiting most of these results and facts to answer basic
      biological questions as yet unresolved. Recent results have shed light on the
      involvement of several genes in red alga reproductive events. In addition, a
      working species characterized by a simple filamentous architecture, easy
      cultivation, and accessible genomes may also facilitate our task. 

PMID- 25755665
TI  - A lane-level LBS system for vehicle network with high-precision BDS/GPS
      positioning.
AB  - In recent years, research on vehicle network location service has begun to focus
      on its intelligence and precision. The accuracy of space-time information has
      become a core factor for vehicle network systems in a mobile environment.
      However, difficulties persist in vehicle satellite positioning since deficiencies
      in the provision of high-quality space-time references greatly limit the
      development and application of vehicle networks. In this paper, we propose a high
      precision-based vehicle network location service to solve this problem. The major
      components of this study include the following: (1) application of wide-area
      precise positioning technology to the vehicle network system. An adaptive
      correction message broadcast protocol is designed to satisfy the requirements for
      large-scale target precise positioning in the mobile Internet environment; (2)
      development of a concurrence service system with a flexible virtual expansion
      architecture to guarantee reliable data interaction between vehicles and the
      background; (3) verification of the positioning precision and service quality in
      the urban environment. Based on this high-precision positioning service platform,
      a lane-level location service is designed to solve a typical traffic safety
      problem.

PMID- 25755664
TI  - Genes and quantitative genetic variation involved with senescence in cells,
      organs, and the whole plant.
AB  - Senescence, the deterioration of morphological, physiological, and reproductive
      functions with age that ends with the death of the organism, was widely studied
      in plants. Genes were identified that are linked to the deterioration of cells,
      organs and the whole plant. It is, however, unclear whether those genes are the
      source of age dependent deterioration or get activated to regulate such
      deterioration. Furthermore, it is also unclear whether such genes are active as a
      direct consequence of age or because they are specifically involved in some
      developmental stages. At the individual level, it is the relationship between
      quantitative genetic variation, and age that can be used to detect the genetic
      signature of senescence. Surprisingly, the latter approach was only scarcely
      applied to plants. This may be the consequence of the demanding requirements for
      such approaches and/or the fact that most research interest was directed toward
      plants that avoid senescence. Here, I review those aspects in turn and call for
      an integrative genetic theory of senescence in plants. Such conceptual
      development would have implications for the management of plant genetic resources
      and generate progress on fundamental questions raised by aging research. 

PMID- 25755666
TI  - Identification and DUS Testing of Rice Varieties through Microsatellite Markers.
AB  - Identification and registration of new rice varieties are very important to be
      free from environmental effects and using molecular markers that are more
      reliable. The objectives of this study were, first, the identification and
      distinction of 40 rice varieties consisting of local varieties of Iran, improved
      varieties, and IRRI varieties using PIC, and discriminating power, second,
      cluster analysis based on Dice similarity coefficient and UPGMA algorithm, and,
      third, determining the ability of microsatellite markers to separate varieties
      utilizing the best combination of markers. For this research, 12 microsatellite
      markers were used. In total, 83 polymorphic alleles (6.91 alleles per locus) were
      found. In addition, the variation of PIC was calculated from 0.52 to 0.9. The
      results of cluster analysis showed the complete discrimination of varieties from
      each other except for IR58025A and IR58025B. Moreover, cluster analysis could
      detect the most of the improved varieties from local varieties. Based on the best
      combination of markers analysis, five pair primers together have shown the same
      results of all markers for detection among all varieties. Considering the results
      of this research, we can propose that microsatellite markers can be used as a
      complementary tool for morphological characteristics in DUS tests. 

PMID- 25755667
TI  - Toll-like receptor-1 and receptor-2 and Beta-defensin in postcholecystectomy bile
      duct injury.
AB  - Postcholecystectomy bile duct injuries (BDI) produce hepatic cholestasis and
      cause infection of the biliary tract. The biliary cells participate in secreting
      cytokines and in expression of immune response receptors. Toll-like receptors
      (TLRs) conduct signalling and activate the innate and adaptive inflammatory
      response. The objective was to determine the serum levels of TLR-2 and the
      expression of TLR-1 and TLR-2 and beta-defensin in liver biopsies of
      postcholecystectomy BDI patients. A transverse, analytical study with 2 groups
      was done. One group included healthy volunteers (control group) and other
      included 25 postcholecystectomy BDI patients with complete biliary obstruction.
      Using the Enzyme-linked Immunosorbent Assay (ELISA) technique, serum levels of
      TLR-2 were determined, and with immunofluorescence the morphologic analysis of
      TLR-1 and TLR-2 and beta-defensin in liver biopsies of postcholecystectomy BDI
      patients was performed. The average TLR-2 serum level in the control group was
      0.0 pg/mL and in the BDI group, 0.023 +/- 0.0045 pg/mL (P < 0.0001, bilateral
      Mann Whitney U). Immunofluorescence was used to determine the expression in liver
      biopsies, blood vessels, bile ducts, and hepatic parenchyma where 12 hepatic
      biopsies were positive for TLR-1 with average of 3213057.74 +/- 1071019.25
      MUm(2); and 7 biopsies were positive for beta-defensin with an average of
      730364.33 +/- 210838.02 MUm(2); and 6 biopsies positive for TLR-2, obtaining an
      average of 3354364.24 +/- 838591.06 MUm(2). In conclusion, TLR-1 and TLR-2 and
      beta-defensin play an important role in the innate antimicrobial defense of the
      hepatobiliary system. 

PMID- 25755668
TI  - Endoplasmic reticulum stress in intestinal epithelial cell function and
      inflammatory bowel disease.
AB  - In eukaryotic cells, perturbation of protein folding homeostasis in the
      endoplasmic reticulum (ER) causes accumulation of unfolded and misfolded proteins
      in the ER lumen, which activates intracellular signaling pathways termed the
      unfolded protein response (UPR). Recent studies have linked ER stress and the UPR
      to inflammatory bowel disease (IBD). The microenvironment of the ER is affected
      by a myriad of intestinal luminal molecules, implicating ER stress and the UPR in
      proper maintenance of intestinal homeostasis. Several intestinal cell
      populations, including Paneth and goblet cells, require robust ER function for
      protein folding, maturation, and secretion. Prolonged ER stress and impaired UPR
      signaling may cause IBD through: (1) induction of intestinal epithelial cell
      apoptosis, (2) disruption of mucosal barrier function, and (3) induction of the
      proinflammatory response in the gut. Based on our increased understanding of ER
      stress in IBD, new pharmacological approaches can be developed to improve
      intestinal homeostasis by targeting ER protein-folding in the intestinal
      epithelial cells (IECs). 

PMID- 25755669
TI  - Bilateral psoas muscle abscess associated with emphysematous cystitis.
AB  - Psoas muscle abscess associated with emphysematous urinary tract infection is
      very rare. There were very few reports about urinary tract infections such as
      renal abscess, perinephric abscess, and emphysematous pyelonephritis complicated
      with psoas muscle abscess; however, psoas muscle abscess associated with
      emphysematous cystitis has not yet been reported. Here, we report a case of
      bilateral posas muscle abscess following emphysematous cystitis in an 81-year-old
      nondiabetic man, who was treated successfully with prolonged antibiotic therapy
      and supportive care. Early recognition of psoas muscle abscess can prevent
      aggressive interventional procedure and warrant good prognosis. 

PMID- 25755670
TI  - Clozapine-Induced Late Agranulocytosis and Severe Neutropenia Complicated with
      Streptococcus pneumonia, Venous Thromboembolism, and Allergic Vasculitis in
      Treatment-Resistant Female Psychosis.
AB  - Clozapine is a second-generation antipsychotic agent from the benzodiazepine
      group indicated for treatment-resistant schizophrenia and other psychotic
      conditions. Using clozapine earlier on once a case appears to be refractory
      limits both social and personal morbidity of chronic psychosis. However treatment
      with second-generation antipsychotics is often complicated by adverse effects. We
      present a case of a 33-year-old Caucasian woman with a 25-year history of
      refractory psychotic mania after switching to a 2-year clozapine therapy. She
      presented clozapine-induced absolute neutropenia, agranulocytosis, which were
      complicated by Streptococcus pneumonia and sepsis. Clozapine-induced
      thromboembolism of the common femoral and right proximal iliac vein, as well as
      allergic vasculitis, was diagnosed. She achieved full remission on granulocyte
      colony stimulating factor and specific antibiotic treatment. Early detection of
      severe clozapine-induced absolute neutropenia and agranulocytosis enabled the
      effective treatment of two among its most severe complications. Additional
      evidence to the previously reported possible causal relation between clozapine
      and venous thromboembolism is offered. Finally, clozapine-induced allergic
      vasculitis is confirmed as a late adverse effect of clozapine therapy. 

PMID- 25755672
TI  - Socioeconomic disadvantage in childhood as a predictor of excessive gestational
      weight gain and obesity in midlife adulthood.
AB  - BACKGROUND: Lower childhood socioeconomic position is associated with greater
      risk of adult obesity among women, but not men. Pregnancy-related weight changes
      may contribute to this gender difference. The objectives of this study were to
      determine the associations between: 1. childhood socioeconomic disadvantage and
      midlife obesity; 2. excessive gestational weight gain (GWG) and midlife obesity;
      and 3. childhood socioeconomic disadvantage and excessive GWG, among a
      representative sample of childbearing women. METHODS: We constructed marginal
      structural models for seven measures of childhood socioeconomic position for 4780
      parous women in the United States, using National Longitudinal Survey of Youth
      (1979-2010) data. Institute of Medicine definitions were used for excessive GWG;
      body mass index >=30 at age 40 defined midlife obesity. Analyses were separated
      by race/ethnicity. Additionally, we estimated controlled direct effects of
      childhood socioeconomic disadvantage on midlife obesity under a condition of
      never gaining excessively in pregnancy. RESULTS: Low parental education, but not
      other measures of childhood disadvantage, was associated with greater midlife
      obesity among non-black non-Hispanic women. Among black and Hispanic mothers,
      childhood socioeconomic disadvantage was not consistently associated with midlife
      obesity. Excessive GWG was associated with greater midlife obesity in all
      racial/ethnic groups. Childhood socioeconomic disadvantage was not statistically
      significantly associated with excessive GWG in any group. Controlled direct
      effects were not consistently weaker than total effects. CONCLUSIONS: Childhood
      socioeconomic disadvantage was associated with adult obesity, but not with
      excessive gestational weight gain, and only for certain disadvantage measures
      among non-black non-Hispanic mothers. Prevention of excessive GWG may benefit all
      groups through reducing obesity, but excessive GWG does not appear to serve as a
      mediator between childhood socioeconomic position and adult obesity in women.

PMID- 25755671
TI  - Transdifferentiation of Human Hair Follicle Mesenchymal Stem Cells into Red Blood
      Cells by OCT4.
AB  - Shortage of red blood cells (RBCs, erythrocytes) can have potentially life
      threatening consequences for rare or unusual blood type patients with massive
      blood loss resulting from various conditions. Erythrocytes have been derived from
      human pluripotent stem cells (PSCs), but the risk of potential tumorigenicity
      cannot be ignored, and a majority of these cells produced from PSCs express
      embryonic epsilon- and fetal gamma-globins with little or no adult beta-globin
      and remain nucleated. Here we report a method to generate erythrocytes from human
      hair follicle mesenchymal stem cells (hHFMSCs) by enforcing OCT4 gene expression
      and cytokine stimulation. Cells generated from hHFMSCs expressed mainly the adult
      beta-globin chain with minimum level of the fetal gamma-globin chain.
      Furthermore, these cells also underwent multiple maturation events and formed
      enucleated erythrocytes with a biconcave disc shape. Gene expression analyses
      showed that OCT4 regulated the expression of genes associated with both
      pluripotency and erythroid development during hHFMSC transdifferentiation toward
      erythroid cells. These findings show that mature erythrocytes can be generated
      from adult somatic cells, which may serve as an alternative source of RBCs for
      potential autologous transfusion. 

PMID- 25755673
TI  - Red peppers with moderate and severe pungency prevent the memory deficit and
      hepatic insulin resistance in diabetic rats with Alzheimer's disease.
AB  - BACKGROUND: Dementia induced by beta-amyloid accumulation impairs peripheral
      glucose homeostasis, but red pepper extract improves glucose homeostasis. We
      therefore evaluated whether long-term oral consumption of different red pepper
      extracts improves cognitive dysfunction and glucose homeostasis in type 2
      diabetic rats with beta-amyloid-induced dementia. METHODS: Male diabetic rats
      received hippocampal CA1 infusions of beta-amyloid (25-35) (AD) or beta-amyloid
      (35-25, non-plaque forming), at a rate of 3.6 nmol/day for 14 days (Non-AD). AD
      rats were divided into four dietary groups receiving either 1% lyophilized 70%
      ethanol extracts of either low, moderate and severe pungency red peppers (AD-LP,
      AD-MP, and AD-SP) or 1% dextrin (AD-CON) in Western diets (43% energy as fat).
      RESULTS: The ascending order of control < LSP < MSP and SSP potentiated the
      phosphorylation of CREB and GSK and inhibited Tau phosphorylation in the
      hippocampus which in turn inhibited beta-amyloid accumulation. The inhibition by
      MP and SP reduced the memory deficit measured by passive avoidance test and water
      maze test. Furthermore, the accumulation of beta-amyloid induced glucose
      intolerance, although serum insulin levels were elevated during the late phase of
      oral glucose tolerance test (OGTT). All of the red pepper extracts prevented the
      glucose intolerance in AD rats. Consistent with OGTT results, during euglycemic
      hyperinulinemic clamp glucose infusion rates were lower in AD-CON than Non-AD-CON
      with no difference in whole body glucose uptake. Hepatic glucose output at the
      hyperinsulinemic state was increased in AD-CON. beta-amyloid accumulation
      exacerbated hepatic insulin resistance, but all red pepper extract treatments
      reversed the insulin resistance in AD rats. CONCLUSIONS: The extracts of moderate
      and severe red peppers were found to prevent the memory deficit and exacerbation
      of insulin resistance by blocking tau phosphorylation and beta-amyloid
      accumulation in diabetic rats with experimentally induced Alzheimer's-like
      dementia. These results suggest that red pepper consumption might be an effective
      intervention for preventing age-related memory deficit.

PMID- 25755674
TI  - Tactics and strategies for managing Ebola outbreaks and the salience of
      immunization.
AB  - We present a stochastic transmission chain simulation model for Ebola viral
      disease (EVD) in West Africa, with the salutary result that the virus may be more
      controllable than previously suspected. The ongoing tactics to detect cases as
      rapidly as possible and isolate individuals as safely as practicable is essential
      to saving lives in the current outbreaks in Guinea, Liberia, and Sierra Leone.
      Equally important are educational campaigns that reduce contact rates between
      susceptible and infectious individuals in the community once an outbreak occurs.
      However, due to the relatively low R 0 of Ebola (around 1.5 to 2.5 next
      generation cases are produced per current generation case in naive populations),
      rapid isolation of infectious individuals proves to be highly efficacious in
      containing outbreaks in new areas, while vaccination programs, even with low
      efficacy vaccines, can be decisive in curbing future outbreaks in areas where the
      Ebola virus is maintained in reservoir populations. 

PMID- 25755675
TI  - Effects of electrode position on spatiotemporal auditory nerve fiber responses: a
      3D computational model study.
AB  - A cochlear implant (CI) is an auditory prosthesis that enables hearing by
      providing electrical stimuli through an electrode array. It has been previously
      established that the electrode position can influence CI performance. Thus,
      electrode position should be considered in order to achieve better CI results.
      This paper describes how the electrode position influences the auditory nerve
      fiber (ANF) response to either a single pulse or low- (250 pulses/s) and high
      rate (5,000 pulses/s) pulse-trains using a computational model. The field
      potential in the cochlea was calculated using a three-dimensional finite-element
      model, and the ANF response was simulated using a biophysical ANF model. The
      effects were evaluated in terms of the dynamic range, stochasticity, and spike
      excitation pattern. The relative spread, threshold, jitter, and initiated node
      were analyzed for single-pulse response; and the dynamic range, threshold,
      initiated node, and interspike interval were analyzed for pulse-train stimuli
      responses. Electrode position was found to significantly affect the
      spatiotemporal pattern of the ANF response, and this effect was significantly
      dependent on the stimulus rate. We believe that these modeling results can
      provide guidance regarding perimodiolar and lateral insertion of CIs in clinical
      settings and help understand CI performance. 

PMID- 25755676
TI  - An overview of loco-regional treatments in patients and mouse models for
      hepatocellular carcinoma.
AB  - Hepatocellular carcinoma is a highly aggressive malignancy and is the third
      leading cause of cancer-related deaths worldwide. Although surgery is currently
      considered the most effective curative treatment for this type of cancer, it is
      note that most of patients have a poor prognosis due to chemioresistence and
      tumor recurrence. Loco-regional therapies, including radiofrequency ablation,
      surgical resection and transcatheter arterial chemoembolization play a major role
      in the clinical management of hepatocellular carcinoma. In order to improve the
      treatment outcome of patients diagnosed with this disease, several in vivo
      studies by using different techniques on cancer mouse models have been performed.
      This review will focus on the latest papers on the efficacy of loco-regional
      therapy and combined treatments in patients and mouse models of hepatocellular
      carcinoma. 

PMID- 25755677
TI  - Evaluation of mechanical properties of esthetic brackets.
AB  - Plastic brackets, as well as ceramic brackets, are used in various cases since
      they have excellent esthetics. However, their mechanical properties remain
      uncertain. The purpose of this study was to determine how deformation and stress
      distribution in esthetic brackets differ among materials under the same wire
      load. Using the digital image correlation method, we discovered the following:
      (1) the strain of the wings of plastic brackets is within 0.2% and that of
      ceramic and metal brackets is negligible, (2) polycarbonate brackets having a
      stainless steel slot show significantly smaller displacement than other plastic
      brackets, and (3) there is a significant difference between plastic brackets and
      ceramic and stainless steel brackets in terms of the displacement of the bracket
      wing. 

PMID- 25755678
TI  - Anaplastic lymphoma kinase (ALK) gene alteration in signet ring cell carcinoma of
      the gastrointestinal tract.
AB  - OBJECTIVES: ALK-EML4 translocation is an established driver aberration in non
      small cell lung cancer (NSCLC), with reported predilection for cases with signet
      ring histology. We assessed the presence of anaplastic lymphoma kinase (ALK) gene
      rearrangements in signet ring cancers arising in the stomach and colon. METHODS:
      Histologically confirmed cases of signet ring adenocarcinoma of the stomach or
      the colon were identified. The presence of the classic ALK and EML4 fusion gene
      was initially determined by fluorescence in-situ hybridization (FISH) technique.
      Immunohistochemistry (IHC) was performed using two previously validated
      antibodies, ALK1 clone (1:100; DAKO) and 5A4 (Novocastra, Leica Biosystems) along
      with positive controls of ALK-translocated lung cancer. RESULTS: We employed 42
      cases of signet ring carcinoma diagnosed between 2001 and 2011; 25 gastric and 17
      colon cancer. Median age 63.3 years; male/female 17/25; race, black 47.5%, white
      47.5%, others, 5%; stage I, 21.4%; stage II, 31%; stage III, 26.2%; stage IV,
      21.4%. One of 42 cases (2.3%) was positive for ALK translocation by FISH using
      the standard criteria of at least 15% positive cells for the break-apart signal
      (50-70 cells enumerated per case). Using a less restrictive cut-off of 10%
      positive cells, 7 cases (16%) were considered possibly positive. None of the
      'possibly positive' cases was found to harbor ALK translocation by another
      molecular testing approach (IHC). IHC with two previously validated monoclonal
      antibodies showed 0 of 42 (0%) cases positive. CONCLUSIONS: ALK gene
      rearrangement is very rare in gastrointestinal cancers and enrichment strategy
      focusing on signet ring cell histology did not significantly improve the
      detection rate.

PMID- 25755679
TI  - Does metabolic syndrome or its components associate with prostate cancer when
      diagnosed on biopsy?
AB  - PURPOSE: To investigate the association between metabolic syndrome and prostate
      cancer risk in Turkish men. METHODS: We examined data from 220 patients with
      prostate cancer and 234 men in a control group with benign biopsy results, who
      had a serum prostate-specific antigen (PSA) level ? 4 ng/ml, or an abnormal
      digital rectal examination finding and who underwent transrectal ultrasound
      guided prostate biopsy at two main training and research hospitals between
      February 2009 and April 2013. Metabolic syndrome was diagnosed according to The
      Society of Endocrinology and Metabolism of Turkey metabolic-syndrome criteria.
      Age, total PSA, waist circumference, body mass index, lipid profiles, fasting
      blood sugar level, blood pressure level and metabolic syndrome were considered
      for analysis. RESULTS: A total of 454 patients were enrolled: 85 cases in group 1
      (38.6% of 220 prostate cancer cases) and 104 control subjects in group 2 (40.4%
      of 234 controls) were diagnosed with metabolic syndrome. Higher ages and lower
      high-density lipoprotein-cholesterol were two parameters that were significant
      only in the prostate cancer group with metabolic syndrome. There was no
      significant predictor factor for prostate cancer alone; however, higher
      triglycerides (odds ratio [OR], 1.286; 95% confidence interval [CI] 1.09-1.82 and
      1.142; 95% CI 1.06-1.62) and fasting glucose levels (OR, 1.222; 95% CI 1.08-1.61
      and 1.024; 95% CI 1.07-1.82) were significant predictors in both the prostate
      cancer group and control group. CONCLUSIONS: We found little evidence to support
      the hypothesis that increased incidence of metabolic syndrome (or its components)
      contributes to increased incidence of prostate cancer. A larger, prospective,
      multicentre investigation is mandatory to confirm if there is any relationship
      between metabolic syndrome and prostate cancer.

PMID- 25755680
TI  - Advanced pancreatic adenocarcinoma: a review of current treatment strategies and
      developing therapies.
AB  - Pancreatic adenocarcinoma is one of the deadliest solid malignancies. A large
      proportion of patients are diagnosed with locally advanced or metastatic disease
      at the time of presentation and, unfortunately, this severely limits the number
      of patients who can undergo surgical resection, which offers the only chance for
      cure. Recent therapeutic advances for patients with advanced pancreatic cancer
      have extended overall survival, but prognosis still remains grim. Given that
      traditional chemotherapy is ineffective in curing advanced pancreatic
      adenocarcinoma, current research is taking a multidirectional approach in the
      hopes of developing more effective treatments. This article reviews the major
      clinical trial data that is the basis for the current chemotherapy regimens used
      as first- and second-line treatments for advanced pancreatic adenocarcinoma. We
      also review the current ongoing clinical trials, which include the use of agents
      targeting the oncogenic network signaling of K-Ras, agents targeting the
      extracellular matrix, and immune therapies. 

PMID- 25755681
TI  - Nivolumab in NSCLC: latest evidence and clinical potential.
AB  - New insight on the interaction between the immune system and tumor has identified
      the programmed death-1/programmed death-1 ligand pathway to be a key player in
      evading host immune response. The immune checkpoint modulator, nivolumab (BMS
      936558/ONO-4538), is the first PD-1 inhibitor to gain regulatory approval, for
      the treatment of patients with unresectable melanoma. This review will discuss
      results from early phase studies of nivolumab in solid tumors including non-small
      cell lung cancer (NSCLC) as well as studies of nivolumab in combination with
      chemotherapy, other immune modulators and molecular targeted therapy in patients
      with NSCLC. 

PMID- 25755682
TI  - Nivolumab in melanoma: latest evidence and clinical potential.
AB  - Melanoma has historically been considered a refractory disease with few if any
      options in the advanced/metastatic setting. Advances in both immune and
      genetically targeted treatment approaches have revolutionized the spectrum of
      treatment options for melanoma patients over the last several years. Recently,
      checkpoint inhibition has become a major focus in the immune-based therapy of
      cancer, especially melanoma. This concept involves inhibition of regulatory cell
      surface molecules which act normally to dampen or modulate T-cell activation.
      Cancer, including melanoma, takes advantage of this physiologic mechanism to turn
      off T-cell activation and prevent effective T-cell antitumor responses.
      Checkpoint inhibitors such as anti cytotoxic T-lymphocyte antigen 4 (anti-CTLA-4)
      and anti programmed death-1 (PD-1) can reverse this immune suppression and
      release T-cell activation. Nivolumab, a monoclonal antibody to the PD-1 receptor,
      promotes antitumor immunity by removing this key negative regulator of T-cell
      activation. In phase I/II studies, promising activity and safety have been
      observed and ongoing phase III trials are comparing nivolumab with other standard
      of care therapies (chemotherapy, ipilimumab). Efficacy may be even further
      increased when used in combination with ipilimumab (albeit with increased
      toxicity). In contrast to typical short-lived responses with cancer therapy in
      metastatic solid tumors, many responses induced by nivolumab appear durable. In
      this review, we discuss the evolution of immune therapy in melanoma leading to
      the development of nivolumab, the clinical experience with this agent, and its
      future development and clinical potential. 

PMID- 25755684
TI  - Management of BRAF and MEK inhibitor toxicities in patients with metastatic
      melanoma.
AB  - Following the discovery that nearly half of all cutaneous melanomas harbour a
      mutation in the BRAF gene, molecular targeted kinase inhibitors have been
      developed for the treatment of metastatic melanoma and have dramatically improved
      outcomes for those patients with BRAF mutant disease, achieving high levels of
      objective response and prolonging survival. Since 2011, the specific BRAF
      targeted agents, vemurafenib and dabrafenib, and the MEK inhibitor, trametinib,
      have been licensed for the treatment of patients with unresectable or metastatic
      BRAF mutant melanoma. As with other biological targeted agents, these drugs are
      associated with predictable patterns of adverse events. Proactive toxicity
      management is important to ensure maximum treatment benefit and avoid unnecessary
      treatment discontinuation. We review the most common and serious adverse events
      associated with BRAF targeted agents and suggest management algorithms to guide
      practitioners in using these drugs effectively in the clinic. 

PMID- 25755683
TI  - Blinded by the light: why the treatment of metastatic melanoma has created a new
      paradigm for the management of cancer.
AB  - Until recently, treatment for metastatic melanoma was characterised by a limited
      availability of treatment options that offer objective survival benefit.
      Cytotoxic agents fundamentally lack the ability to achieve disease control and
      cytokine therapy with interleukin-2 has an unacceptably high - for the use across
      all patient cohorts - rate of toxicities. The validation of braf as an oncogene
      driving melanoma tumorigenesis, as well as the discovery of the role of CTLA-4
      receptor in the evasion of anticancer immune response by melanoma, has
      revolutionised our treatment options against a disease with dismal prognosis.
      Quick implementation of translational discoveries brought about BRAF/MEK
      inhibition in clinic, while at the same time, wider experience with CTLA-4
      blockade enabled clinicians to manage previously fatal immune-related toxicities
      with greater confidence. The suitability for clinical use of other oncogenic
      drivers such as NRAS and c-kit is currently being tested whilst the PD-1/PD-L1/PD
      L2 axis has emerged as a new immunotherapy target with exciting early phase
      results. The recent exponential progress in treatment of melanoma has set an
      example of translational medicine and the current review aims to explain why, as
      well as suggesting new goals for the future. 

PMID- 25755685
TI  - Responder analysis of a randomized comparison of the 13.3 mg/24 h and 9.5 mg/24 h
      rivastigmine patch.
AB  - INTRODUCTION: OPtimizing Transdermal Exelon In Mild-to-moderate Alzheimer's
      disease (OPTIMA) was a randomized, double-blind comparison of 13.3 mg/24 h versus
      9.5 mg/24 h rivastigmine patch in patients with mild-to-moderate Alzheimer's
      disease who declined despite open-label treatment with 9.5 mg/24 h patch. Over 48
      weeks of double-blind treatment, high-dose patch produced greater functional and
      cognitive benefits compared with 9.5 mg/24 h patch. METHODS: Using OPTIMA data, a
      post-hoc responder analysis was performed to firstly, compare the proportion of
      patients demonstrating improvement or absence of decline with 13.3 mg/24 h versus
      9.5 mg/24 h patch; and secondly, identify predictors of improvement or absence of
      decline. 'Improvers' were patients who improved on the Alzheimer's Disease
      Assessment Scale-cognitive subscale (ADAS-cog) by >=4 points from baseline, and
      did not decline on the instrumental domain of the Alzheimer's Disease Cooperative
      Study-Activities of Daily Living scale (ADCS-IADL). 'Non-decliners' were patients
      who did not decline on either scale. RESULTS: Overall, 265 patients randomized to
      13.3 mg/24 h and 271 to 9.5 mg/24 h patch met the criteria for inclusion in the
      intention-to-treat population and were included in the analyses. Significantly
      more patients were 'improvers' with 13.3 mg/24 h compared with 9.5 mg/24 h patch
      at Weeks 24 (44 (16.6%) versus 19 (7.0%); P < 0.001) and 48 (21 (7.9%) versus 10
      (3.7%); P = 0.023). A significantly greater proportion of patients were 'non
      decliners' with 13.3 mg/24 h compared with 9.5 mg/24 h patch at Week 24 (71
      (26.8%) versus 44 (16.2%); P = 0.002). At Week 48, there was a trend in favor of
      13.3 mg/24 h patch. Functional and cognitive assessment scores at double-blind
      baseline did not consistently predict effects at Weeks 24 or 48. CONCLUSION: More
      patients with mild-to-moderate Alzheimer's disease who are titrated to 13.3 mg/24
      h rivastigmine patch at time of decline are 'improvers' or 'non-decliners' i.e.
      show responses on cognition and activities of daily living compared with patients
      remaining on 9.5 mg/24 h patch. TRIAL REGISTRATION: Clinicaltrials.gov
      identifier: NCT00506415; registered July 20, 2007.

PMID- 25755686
TI  - Aberrant DNA methylation of imprinted loci in hepatocellular carcinoma and after
      in vitro exposure to common risk factors.
AB  - BACKGROUND: Hepatocellular carcinoma (HCC) is among the most frequent human
      malignancies and a major cause of cancer-related death worldwide. It is
      characterized by late detection and fast progression, and it is believed that
      epigenetic disruption may be one of the molecular mechanisms leading to
      hepatocarcinogenesis. Previous studies from our group revealed that HCC tumors
      exhibit specific DNA methylation signatures associated with major risk factors
      and tumor progression. Imprinted genes are mono-allelically expressed in a parent
      of-origin-dependent manner and have been suggested to be more susceptible to
      deregulation in cancer. To test this notion, we performed a targeted analysis of
      DNA methylation in known imprinted genes, using HCC samples and in vitro models
      of carcinogenic exposure. RESULTS: Analysis of HCC DNA methylation in two
      independent datasets showed that differentially methylated loci are significantly
      enriched in imprinted genes. Most of the promoters of imprinted genes were found
      hypomethylated in HCC tumors compared to surrounding tissues, contrasting with
      the frequent promoter hypermethylation observed in tumors. We next investigated
      the status of methylation of the imprinting control region (ICR) of different
      imprinted clusters and found that the 15q11-13 ICR was significantly
      hypomethylated in tumors relative to their surrounding tissues. In addition,
      expression of imprinted genes within this cluster was frequently deregulated in a
      gene-specific manner, suggesting distinct mechanisms of regulation in this
      region. Finally, primary human hepatocytes and hepatocyte-like HepaRG cells
      displayed higher methylation variability in certain imprinted loci after natural
      hepatitis B virus (HBV) infection and after lipid accumulation, respectively.
      CONCLUSION: The methylation status of a large panel of imprinted genes was found
      deregulated in HCC, suggesting a major role of this mechanism during
      hepatocarcinogenesis. In vitro models support the hypothesis of imprinted gene
      methylation as a potential marker of environmental exposures.

PMID- 25755687
TI  - Influence of local meteorology and NO2 conditions on ground-level ozone
      concentrations in the eastern part of Texas, USA.
AB  - The influence of local climatic factors on ground-level ozone concentrations is
      an area of increasing interest to air quality management in regards to future
      climate change. This study presents an analysis on the role of temperature, wind
      speed, wind direction, and NO2 level on ground-level ozone concentrations over
      the region of Eastern Texas, USA. Ozone concentrations at the ground level depend
      on the formation and dispersion processes. Formation process mainly depends on
      the precursor sources, whereas, the dispersion of ozone depends on meteorological
      factors. Study results showed that the spatial mean of ground-level ozone
      concentrations was highly dependent on the spatial mean of NO2 concentrations.
      However, spatial distributions of NO2 and ozone concentrations were not uniformed
      throughout the study period due to uneven wind speeds and wind directions. Wind
      speed and wind direction also played a significant role in the dispersion of
      ozone. Temperature profile in the area rarely had any effects on the ozone
      concentrations due to low spatial variations.

PMID- 25755688
TI  - Genomic and non-genomic effects of glucocorticoids: implications for breast
      cancer.
AB  - Glucocorticoids (GC) are essential steroid hormones for human life. They regulate
      a series of important processes by binding with three glucocorticoid receptors
      (GR) and activating genomic and non-genomic pathways. Activated cytoplasmic GR
      can directly bind DNA and transactivate or transrepress specific genes.
      Additionally, it can interact with other transcription factors to affect gene
      expression indirectly. The two membrane GR can interact with mitogen-activated
      protein (MAP) kinases or activate cAMP and Ca(2+)-dependent pathways,
      respectively. Glucocorticoids have been widely used as co-treatment of patients
      with breast cancer (BC) due to reduction of chemotherapy-induced side effects
      such as nausea, lack of appetite, and inflammation. However, GC may exert a
      direct effect on tumor response to chemotherapy. In vitro, GC inhibits
      chemotherapy, radiation and cytokine-induced apoptosis by upregulating
      antiapoptotic genes and detoxifying proteins. They also upregulate the proto
      oncogene c-fms, tumor suppressor gene Nm23, several members of the epidermal
      growth factor (EGF) signaling pathway and the estrogen sulfotransferase signaling
      pathway, thus indirectly inhibiting estrogen receptor activation. They inhibit
      the proangiogenic gene (vascular endothelial growth factor (VEGF); Therefore,
      they could play a role in reducing angiogenesis. Interestingly, the
      phosphorylation status of ser-211 in the GR is dependent on the expression of the
      BRCA1 gene, a tumor suppressor gene that is mutated in the majority of patients
      with triple negative BC. Some clinical randomized trials have also attempted to
      address the effect of GC on patients with BC. Thus, in this review we summarize
      GC mechanisms of action and their participation in several facets of BC. 

PMID- 25755689
TI  - Therapeutic effect comparison of hepatocyte-like cells and bone marrow
      mesenchymal stem cells in acute liver failure of rats.
AB  - GOALS: To evaluate the therapeutic efficacy of rat bone marrow mesenchymal stem
      cells (BMSCs) induced into hepatocyte-like cells and of un-induced BMSCs in acute
      liver failure rats. METHODS: BMSCs in highly homogenous passage 3 were cultured
      using the whole bone marrow adherent culture method. Hepatic-related characters
      were confirmed with morphology, RT-PCR analysis, glycogen staining and albumin
      (ALB) immunofluorescence assay. Carbon tetrachloride (CCl4) was injected
      intraperitoneally to establish an acute rat liver failure model. Hepatocyte-like
      cells or un-induced BMSCs were respectively injected into the models to examine
      rats' appearance, liver function assay and liver tissue pathology. RESULTS:
      Hepatocyte-like morphology, higher expression of cytokeratin 18 (CK18) mRNA and
      ALB protein, and glycogen accumulation were confirmed in the induced BMSCs. The
      transplanted DAPI-labeled BMSCs were localized in the liver tissue 3-14 days
      after transplantation. The levels of liver function indicators (AST, ALT, ALP,
      and TBIL) from transplanted rats were significant decreased and pathology was
      improved, indicating the recovery of liver function. However, the differences
      were statistically insignificant. CONCLUSION: Both hepatocyte-like cells and un
      induced BMSCs had a similarly positively therapeutic efficacy on liver
      regeneration in rat liver failure model.

PMID- 25755690
TI  - Isorhamnetin flavonoid synergistically enhances the anticancer activity and
      apoptosis induction by cis-platin and carboplatin in non-small cell lung
      carcinoma (NSCLC).
AB  - The development of novel antitumor drugs for the treatment of non-small cell lung
      carcinoma NSCLC is imperative in order to improve the efficacy of lung cancer
      therapy and prognosis. In the current study, we demonstrated the antitumor
      activity of isorhamnetin and its combinations with cisplatin and carboplatin
      against A-549 lung cancer cells. In order to assess the anticancer enhancing
      effect of isorhamnetin on cisplatin and carboplatin, A-549 cells were treated
      with isorhamnetin, cisplatin, carboplatin and their combinations and cell
      viability, cell apoptosis, cell cycle arrest as well as loss of mitochondrial
      membrane potential were evaluated by MTT assay, flow cytometry, confocal
      microscopy and fluorescence microscopy. The effect of the drugs on cancer cell
      migration, microtubule depolymerization as well activation of caspases was also
      studied. The results revealed that, as compared to single drug treatment, the
      combination of isorhamnetin with cisplatin and carboplatin resulted in greater
      effect in inhibiting cancer cell growth and inducing apoptosis. Combination of
      isorhamnetin with cisplatin and carboplatin resulted in more potent apoptosis
      induction as revealed by fluorescence microscopy using AO/PI double staining.
      Isorhamnetin and its combinations also triggered microtubule distortion and
      depolymerization. The combination of isorhamnetin with cisplatin and carboplatin
      increased the number of cells in G2/M phase dramatically as compared to single
      drug treatment. Moreover, isorhamnetin and its combinations with known anticancer
      drugs induced disruption of the mitochondrial membrane potential as well as
      activation of caspases 3, 9 and poly-(ADP-ribose) polymerase in A-549 cells.
      Isorhamnetin as well as its combinations with cisplatin and carboplatin resulted
      in inhibition of cancer cell migration significantly. Results of the current
      study suggest that isorhamnetin combinations with cisplatin and carboplatin might
      be a potential clinical chemotherapeutic approach for NSCLC. 

PMID- 25755691
TI  - Genomic analysis of drug resistant pancreatic cancer cell line by combining long
      non-coding RNA and mRNA expression profling.
AB  - Recently, more and more studies show that long non-coding RNAs (lncRNAs) play a
      very important role in various biological processes. However, research on lncRNA
      in the tumor cell drug resistance of it is seldom reported. In this study,
      gemcitabine-resistant pancreatic cancer cell line SWl990/GZ was obtained by
      treating parental cell line SWl990 in vitro with increasing dosage of gemcitabine
      in culture medium intermittently for ten months. We identified 4983 of 13310
      detected lncRNAs demonstrated > 2-fold abnormally expressed in response to the
      gemcitabine-resistant, among of them, 1993 and 2990 lncRNAs were upregulated and
      downregulated. Meanwhile, 4759 mRNAs exhibited at least a 2-fold, of these, 2671
      and 2088 mRNAs were upregulated and downregulated. Gene Ontology analysis and
      Pathway analysis revealed that differential expression mRNA involved in
      significant biological regulatory function and some genes may be particular to
      pancreatic cancer chemotherapy resistance. Quantitative real time PCR confirmed
      the changes of six lncRNAs (RP11-58D2.1, lincRNA-ZNF532, AP000221.1, CTC
      338M12.5, CR619813, DDX6P) and nine mRNAs (SYT1, FAM171B, ZNF331, FAM187B,
      CYP1A1, SRXN1, HIST1H2BL, TOMM40L and SPP1) in SW1990 and SW1990/GZ. We also
      found that the upregulating of gemcitabine on the expression of lincRNA-ZNF532
      was time-dependent. Gemcitabine at a range from 1.0 MUM to 16.0 MUM induced a
      increase of lincRNA-ZNF532 in SW1990 cells. The relative level of DDX6P is
      opposite to that of lincRNA-ZNF53 in the same circumstance. In conclusion, the
      dysregulated lncRNAs and mRNAs identified in this work may represent good
      candidates for future diagnostic or prognostic biomarkers and therapeutic
      targets.

PMID- 25755692
TI  - Paeoniflorin protects HUVECs from AGE-BSA-induced injury via an autophagic
      pathway by acting on the RAGE.
AB  - The aim of our study was to investigate the protective effects of Paeoniflorin
      (PF) against injury induced by AGE-modified bovine serum albumin (AGE-BSA) in
      human umbilical vein endothelial cells (HUVECs), and to examine the underlying
      mechanisms of these effects. A 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl
      tetrazolium bromide (MTT) assay was used to determine cell viability. Protein
      expression levels were determined by western blotting. For function-blocking
      experiments, we used small interfering RNA molecules (siRNA) for function
      blocking experiments. At 6 h, we found that 100 MUg/mL AGE-BSA reduced the
      viability of HUVECs. However, pretreatment with PF restored cell viability in a
      dose-dependent manner. AGE-BSA increased the levels of microtubule-associated
      protein light chain 3-II (LC3-II) and the receptor for advanced glycation end
      products (RAGE). Expression of p62 protein was also increased, but not at a
      statistically significant level. Pretreatment with PF further increased levels of
      LC3-II and RAGE, but reduced the expression of p62. In cells transfected with
      Atg5 and RAGE siRNA, cell viability and expression of LC3-II decreased in both
      the AGE-BSA and PF + AGE-BSA treatments. PF can protect HUVECs from AGE-BSA
      induced injury by upregulating autophagy and promoting the completion of
      autophagy flux. RAGE plays an important role in this autophagic protection
      effect. 

PMID- 25755693
TI  - Wogonoside induces cell cycle arrest and mitochondrial mediated apoptosis by
      modulation of Bcl-2 and Bax in osteosarcoma cancer cells.
AB  - Osteosarcoma (OS) is the most common bone cancer with a great tendency for local
      invasion and distant metastasis. Restricted by the severe toxicity of
      conventional drugs, the therapeutic challenge of osteosarcoma still remains
      unconquered. The objective of the present research work was to investigate the
      antiproliferative activity of wogonoside against human osteosarcoma (SaOS-2) cell
      line. Cell viability after wogonoside treatment was evaluated by MTT assay. Phase
      contrast microscopy was used to evaluate the change in cell morphology following
      drug treatment. The effect of wogonoside on cell cycle phase distribution and
      mitochondrial membrane potential was investigated by flow cytometry using
      propidium iodide (PI) and rhodamine-123 DNA-binding fluorescent dyes
      respectively. Western blotting was used to evaluate the effect of wogonoside on
      cell cycle-related proteins as well as on the expression levels of Bcl-2, Bax,
      cytosolic and mitochondrial cytochrome c and apoptotic protease activating factor
      1 (Apaf-1). Wogonoside induced a dose-dependent as well as time-dependent growth
      inhibitory effects on cell proliferation of SaOS-2 cancer cells. Wogonoside
      induced G2/M cell cycle arrest as well as loss in mitochondrial membrane
      potential in these cells. Within 48 h of incubation, approximately 4.36%, 6.72%,
      11.54%, 21.88% and 15.54% of the cells underwent early apoptosis after treatment
      with 0, 5, 10, 25 and 75 MUM of wogonoside respectively. Wogonoside led to
      reduced Bcl-2 expression and increased Bax expression, while as it led to s
      decrease in the levels of mitochondrial cytochrome c and an increase in cytosolic
      fraction and expressions of cytosolic apoptotic protease activating factor-1
      (Apaf-1). 

PMID- 25755694
TI  - Cartilage engineering using chondrocyte cell sheets and its application in
      reconstruction of microtia.
AB  - The imperfections of scaffold materials have hindered the clinical application of
      cartilage tissue engineering. The recently developed cell-sheet technique is
      adopted to engineer tissues without scaffold materials, thus is considered being
      potentially able to overcome the problems concerning the scaffold imperfections.
      This study constructed monolayer and bilayer chondrocyte cell sheets and
      harvested the sheets with cell scraper instead of temperature-responsive culture
      dishes. The properties of the cultured chondrocyte cell sheets and the
      feasibility of cartilage engineering using the chondrocyte cell sheets was
      further investigated via in vitro and in vivo study. Primary extracellular matrix
      (ECM) formation and type II collagen expression was detected in the cell sheets
      during in vitro culture. After implanted into nude mice for 8 weeks, mature
      cartilage discs were harvested. The morphology of newly formed cartilage was
      similar in the constructs originated from monolayer and bilayer chondrocyte cell
      sheet. The chondrocytes were located within evenly distributed ovoid lacunae.
      Robust ECM formation and intense expression of type II collagen was observed
      surrounding the evenly distributed chondrocytes in the neocartilages. Biochemical
      analysis showed that the DNA contents of the neocartilages were higher than
      native human costal cartilage; while the contents of the main component of ECM,
      glycosaminoglycan and hydroxyproline, were similar to native human costal
      cartilage. In conclusion, the chondrocyte cell sheet constructed using the simple
      and low-cost technique is basically the same with the cell sheet cultured and
      harvested in temperature-responsive culture dishes, and can be used for cartilage
      tissue engineering. 

PMID- 25755695
TI  - In vitro effects of platinum compounds on renal cellular respiration in mice.
AB  - BACKGROUND: Cisplatin, carboplatin and oxaliplatin are structurally-related
      compounds, which are commonly used in cancer therapy. Cisplatin (Platinol((r)))
      has Boxed Warning stating: "Cumulative renal toxicity associated with PLATINOL is
      severe", while carboplatin and oxaliplatin are less nephrotoxic. These drugs form
      platinum adducts with cellular DNA. Their bindings to cellular thiols (e.g.,
      glutathione and metallothionein) are known to contribute to drug resistance while
      thiol depletion augments platinum toxicity. METHODS: Using phosphorescence oxygen
      analyzer, this study investigated the effects of platinum drugs on renal cellular
      respiration (mitochondrial O2 consumption) in the presence and absence of the
      thiol blocking agent N-ethylmaleimide (used here as a model for thiol depletion).
      Renal cellular ATP was also determined. Kidney fragments from C57BL/6 mice were
      incubated at 37  degrees C in Krebs-Henseleit buffer (gassed with 95% O2:5% CO2)
      with and without 100 MUM platinum drug in the presence and absence of 100 MUM N
      ethylmaleimide for <= 6 h. RESULTS: Platinum drugs alone had no effects on
      cellular respiration (P >= 0.143) or ATP (P >= 0.161). N-ethylmaleimide lowered
      cellular respiration (P <= 0.114) and ATP (P = 0.008). The combination of
      platinum drug and N-ethylmaleimide significantly lowered both cellular
      respiration (P <= 0.006) and ATP (P <= 0.003). Incubations with N-ethylmaleimide
      alone were associated with moderate-to-severe tubular necrosis. Incubations with
      cisplatin+N-ethylmaleimide vs. cisplatin alone produced similar severities of
      tubular necrosis. Tubular derangements were more prominent in carboplatin+N
      ethylmaleimide vs. carboplatin alone and in oxaliplatin+N-ethylmaleimide vs.
      oxaliplatin alone. CONCLUSIONS: These results demonstrate the adverse events of
      thiol depletion on platinum-induced nephrotoxicities. The results suggest
      cellular bioenergetics is a useful surrogate biomarker for assessing drug-induced
      nephrotoxicities.

PMID- 25755696
TI  - FOXA1 positively regulates gene expression by changing gene methylation status in
      human breast cancer MCF-7 cells.
AB  - OBJECTIVE: DNA methylation is an important epigenetic modification with tumor
      suppressor gene silencing in cancer. The mechanisms underlying DNA methylation
      patterns are still poorly understood. This study aims to evaluate the potential
      value of FOXA1 for controlling gene CpG island methylation in breast cancer.
      METHODS: FOXA1 was down-regulated by transfection with siRNA and up-regulated by
      transfection with plasmid in MCF-7 cell lines. The DNA methylation and mRNA
      levels were examined by qMSP and qRT-PCR. The cell proliferation and apoptosis
      was detected by MTT and Flow cytometry. RESULTS: Suppression of FOXA1 enhanced
      the methylation status of DAPK, MGMT, RASSF1A, p53, and depressed mRNA levels of
      these tumor suppressor genes, whereas over-expression of FOXA1 showed the
      opposite effects. DNMT1, DNMT3A and DNMT3B mRNA were up-regulated by siRNA knock
      down of FOXA1. At the same time, FOXA1 suppression promoted cell growth and
      inhibited apoptosis. CONCLUSIONS: FOXA1 may be associated with methylation of the
      tumor suppressor genes promoter through changing DNMTs expression. FOXA1 could be
      a potential demethylation target for prevention and treatment of breast cancer.

PMID- 25755697
TI  - Bone marrow-derived mesenchymal stem cells inhibits hepatocyte apoptosis after
      acute liver injury.
AB  - OBJECTIVE: To investigate the protective effect of bone marrow-derived
      mesenchymal stem cells (BMSCs) transplantation on acute liver injury (ALI) rats.
      MATERIAL AND METHODS: BMSCs were extracted from rat bone marrow, cultured and
      expansion in vitro, and identified by flow cytometer. Rat model with acute liver
      injury was established by employing D-galactosamine and Lipopolysaccharide. Male
      rats were randomly divided into ALI model group and BMSCs transplantation group.
      Rats were sacrificed 24 h, 72 h and 120 h after BMSCs injection to determine
      alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels in
      serum. Proliferating cell nuclear antigen (PCNA) immunohistochemistry staining
      and quantitative reverse transcription polymerase chain reaction (RT-PCR) of
      alpha-fetoprotein (AFP) and glypican-3 (GPC3) were performed to analysis
      proliferation. Terminal deoxynucleontidyl Transferase Biotin-dUTP Nick End
      Labeling (TUNEL) assays were used to analyze apoptosis and mitochondria-dependent
      pathway related factors Bax and Bcl-2 were examined by Western blot. RESULTS:
      Compared with the ALI model group, the BMSCs transplantation group presented the
      lower levels of ALT, AST, decreased Bax proteins expression, and increased Bcl-2
      expression. The mRNA levels of AFP and GPC3 and expression of PCNA were
      significantly higher in BMSCs transplantation group. CONCLUSIONS: BMSCs
      transplantation could significantly restore liver function. These effects were
      supposed to be mediated by suppressing hepatocyte apoptosis as well as promoting
      proliferation. Reduction of apoptosis seemed to correlate with mitochondria
      dependent-pathway.

PMID- 25755698
TI  - HIF-1alpha change in serum and callus during fracture healing in ovariectomized
      mice.
AB  - The purpose was to detect the effects of ovariectomy (OVX) on femoral fracture
      healing through different angiogenesis and HIF-1alpha expression in mice. Thirty
      six young female C57 mice were randomized into two groups: OVX and age-matched
      intact control (CON). The femoral fracture was generated at 3 weeks after OVX or
      CON. At 2 or 4 weeks after fracture, the femoral fracture area was evaluated
      healing status by bone mineral density (BMD), callus formation and mineralization
      and neovascularization in callus, biomechanical analysis, and HIF-1alpha tests.
      OVX mice showed lower BMD as compared with CON mice. Callus geometric
      microstructural parameters of the femora in OVX mice were significantly lower
      than CON mice. OVX induced significant changes of biomechanical parameters in the
      femoral fracture healing area. The callus forming, callus neovascularization and
      HIF-1alpha tests in OVX mice were significantly lower than in CON mice. HIF
      1alpha results have the positive proportion with osteoporotic fracture healing. 

PMID- 25755699
TI  - MOK overexpression is associated with promoter hypomethylation in patients with
      acute myeloid leukemia.
AB  - Overexpression of MAPK/MAK/MRK overlapping kinase (MOK) has been found in various
      tumors. However, the mechanism underlying MOK upregulation remains unclear. A CpG
      island was identified in MOK promoter. In this study, we evaluated the expression
      and methylation status of MOK gene in acute myeloid leukemia (AML).
      Hypomethylation of MOK promoter was detected in 31.0% (45/145) of AML patients.
      The degree of MOK hypomethylation was significantly correlated with MOK
      expression in AML patients. MOK-hypomethylated patients had a trend towards lower
      WBCs. Receiver operating characteristic curve (ROC) analysis showed a good
      performance in distinguishing AML patients from controls with an area under the
      ROC curve (AUC) of 0.820 (P < 0.001). In summary, our results suggest MOK
      promoter hypomethylation is a common event and contributes to MOK overexpression
      in AML. 

PMID- 25755701
TI  - Contribution of calcium-activated chloride channel to elevated pulmonary artery
      pressure in pulmonary arterial hypertension induced by high pulmonary blood flow.
AB  - The correlation between calcium-activated chloride channel (CaCC) and pulmonary
      arterial hypertension (PAH) induced by high pulmonary blood flow remains
      uncertain. In this study, we investigated the possible role and effects of CaCC
      in this disease. Sixty rats were randomly assigned to normal, sham, and shunt
      groups. Rats in the shunt group underwent abdominal aorta and inferior vena cava
      shunt surgery. The pulmonary artery pressure was measured by catheterization.
      Pathological changes, right ventricle hypertrophy index (RVHI), arterial wall
      area/vessel area (W/V), and arterial wall thickness/vessel external diameter
      (T/D) were analyzed by optical microscopy. Electrophysiological characteristics
      of pulmonary arterial smooth muscle cells (PASMCs) were investigated using patch
      clamp technology. After 11 weeks of shunting, PAH and pulmonary vascular
      structural remodeling (PVSR) developed, accompanied by increased pulmonary
      pressure and pathological interstitial pulmonary changes. Compared with normal
      and sham groups, pulmonary artery pressure, RVHI, W/V, and T/D of the shunt group
      rats increased significantly. Electrophysiological results showed primary CaCC
      characteristics. Compared with normal and sham groups, membrane capacitance and
      current density of PASMCs in the shunt group increased significantly, which were
      subsequently attenuated following chloride channel blocker niflumic acid (NFA)
      treatment. To conclude, CaCC contributed to PAH induced by high pulmonary blood
      flow and may represent a potential target for treatment of PAH. 

PMID- 25755700
TI  - Analysis of T-cell epitopes of Der f3 in Dermatophagoides farina.
AB  - House dust mites (HDM) are most important indoor allergens for humans. Der f3,
      one of the potent allergens with allergenicity, is derived from Dermatophagoides
      farina (D. farinae), and exhibits strong allergenicity that was confirmed in our
      previous work. The current study was undertaken to determine the localization of
      T-cell epitope of Der f3. We initially developed the T-cell fraction from BALB/c
      mice sensitized with recombinant Der f3 to determine the T-cell epitopes in the
      murine models, and performed T cell proliferation assay with 25 synthetic
      overlapping peptides of Der f3. The results indicated that T-cell reactive region
      of murine were assigned on amino acid range 41-60, 101-120, 161-180 and 201-220,
      respectively. In addition, we did T-cell proliferation experiment, respectively
      using the 4 murine T-cell epitope peptide and the human T-cell lines from three
      patients allergic to mite allergens in order to verify homogenous T-cell epitopes
      in humans. The results indicated that the amino acid sequences of 41-60, 101-120
      and 161-180 had induced T cell proliferation in humans, yet 201-220 failed to.
      These findings suggest that T-cell epitope in Der f3 is located in the amino acid
      sequences of 41-60, 101-120 and 161-180, respectively. T-cell epitope
      localization detected in our study may provide a basis for development of animal
      therapeutic model and peptide vaccine for asthma. 

PMID- 25755702
TI  - 3-cinnamoyl-4-hydroxy-6-methyl-2H-pyran-2-one (CHP) inhibits human ovarian cell
      proliferation by inducing apoptosis.
AB  - Coumarins induce apoptosis by activating mitochondrial pathway and caspase-3
      dependent apoptotic pathway. In the present study, we first time investigated the
      effect of 3-cinnamoyl-4-hydroxy-6-methyl-2H-pyran-2-one (CHP) on induction of
      apoptosis in human ovarian carcinoma cells. The data from MTT assay revealed a
      significant inhibitory effect on cell viability at 30 (87%) and 50 MUM (74%)
      concentration of CHP in OVCAR-3 and OVCAR-420 cells, respectively after 72 h.
      Apoptosis analysis using annexin V/PI double staining followed by flow cytometry
      showed 59 and 52% binding to annexin V-FITC in OVCAR-3 and OVCAR-420 cells
      respectively. propidium iodide (PI) staining and flow cytometry examination
      indicated a significant increase in percentage of cells in G2/M phase after
      treatment with CHP compared to DMSO control group. Reactive oxygen species (ROS)
      assay kit showed increase in levels of ROS. We used rhodamine-123 (Rh-123)
      staining and flow cytometry assay to determine changes in mitochondrial membrane
      potential (LambdaPsim). The results revealed that CHP significantly decreased MMP
      to 85.65 +/- 1.2443% & 49.78 +/- 1.6554% at 10 and 30 MUM respectively in OVCAR-3
      compared to 95.97 +/- 2.1243% in control group. Western blot analysis clearly
      indicated a significant increase in the expression of Caspase-3, Bax, and release
      of Cytochrome c and decrease in Bcl-2, CDK1 and Cyclin B1 expression on treatment
      with CHP. Therefore, CHP may become a potential candidate for the treatment of
      human ovarian cancers. 

PMID- 25755703
TI  - Solitary juvenile xanthogranuloma with tibial involvement: a case report.
AB  - Juvenile xanthogranuloma (JXG) is a rare disease that is part of a spectrum of
      histiocytic dendritic cell disorders. Most patients present with a solitary
      cutaneous lesion; however, others present with extracutaneous manifestations or
      even with systemic involvement. We present the first report of an 11-month-old
      girl in whom was diagnosed a unifocal extracutaneous JXG involving the tibia.
      Histological and immunohistochemical staining results are presented. A review of
      the literature on these unusual lesions is conducted, along with discussion of
      their differential diagnosis and key aspects of the patient's evaluation,
      management, and pathological diagnosis. 

PMID- 25755704
TI  - JARID1B deletion induced apoptosis in Jeko-1 and HL-60 cell lines.
AB  - AIMS: To investigate the involvement of JARID1B histone methyltransferase in the
      epigenetic change of euchromatic promoter in mantle cell lymphoma (MCL) and acute
      leukemia. METHODS: We retrospectively analyzed the protein of JARID1B and tri
      methylated histone H3 lysine 4 (H3K4), histone H3 lysine 9 (H3K9), and cyclin D1
      and Ki67 in 30 cases of MCL by immunohistochemistry. JARID1B was depleted by
      small interfering RNA (siRNA), and cell apoptosis and cell proliferation were
      detected by flow cytometry and MTT [3-(4,5-dimethylthiazol-2-yl)-2, 5
      diphenyltetrazolium bromide], histone tri-methylated H3K4 and histone acetylated
      H3, H4, cyclin D1, Bcl-2, procaspase-3, C-myc were studied by Western blot.
      RESULTS: We demonstrated that JARID1B was upregulated and histone tri-methylated
      H3K4 was downregulated in MCL compared to proliferative lymphadenitis, P < 0.05.
      The expression of histone methylated H3K9 was similar in both. Histone
      methylation of H3K4 was positively correlated with Ki67 in MCL (Kappa = 0.757, P
      < 0.05). This study showed that depletion of JARID1B cleavage apoptotic proteins
      of Bcl-2, procaspase-3, C-myc and resulted in loss cell viability and inducing
      apoptosis in Jeko-1 and HL-60 cell lines. JARID1B siRNA improved tri-methyl H3K4
      and histone acetylated H3 and inhibited cyclin D1, but did not affect histone
      acetylated H4. CONCLUSIONS: This study revealed hyper JARID1B expression and hypo
      histone H3K4 tri-methylation in MCL. We identify depletion JARID1B as a
      demethylase which is capable of removing three methyl groups from H3K4 and up
      regulating histone acetylation of H3 in both cell lines. Interestingly, depletion
      of JARID1B inhibits Cyclin D1, which is one of the genes contributes to MCL
      pathogenesis. JARID1B might be one of therapeutic targets in acute leukemia and
      MCL.

PMID- 25755705
TI  - Swertianlarin, isolated from Swertia mussotii Franch, increases detoxification
      enzymes and efflux transporters expression in rats.
AB  - Swertianlarin, isolated from Swertia mussotii Franch and Enicostemma axillare,
      has hepatoprotective effects against cholestasis in rat models of hepatotoxicity.
      However, the underlying molecular mechanism is not clear. We then treated rats
      with swertianlarin for 7 d and then measured serum liver injury markers, lipids,
      and bile salts, as well as the expression of bile acid synthesis and
      detoxification enzymes (e.g. Cyp7a1 and Cyp3a), membrane influx and efflux
      transporters (e.g. Ntcp and Mrp3), nuclear receptors (e.g. Pxr and Fxr/Shp) and
      transcriptional factors (e.g. Nrf2 and Hnf3beta) in the liver. We found a
      significant induction of the expression of the basolateral efflux transporters
      Mrp3 and Mrp4 and canalicular transporter Mdr1 in rats treated with
      swertianlarin, compared with the controls (1.9-fold and 2.2-fold, P < 0.005, and
      3.4-fold, P < 0.05, respectively). The expression of detoxification enzymes
      Cyp3a, Ugt2b, Sult2a1 and Gsta1 in rats treated with swertianlarin was
      significantly higher than that in controls (3.7-fold, 2.8-fold, 2.1-fold, and 1.7
      fold, respectively, all P < 0.05). Expression of the synthetic enzyme, Cyp8b1,
      was higher in rats treated with swertianlarin than that in controls (1.8-fold at
      mRNA level and 3.4-flod at protein level, P < 0.05). Elevated serum levels of the
      conjugated bile acids, taurocholic acid and taurodeoxycholic acid, and a
      reduction in levels of serum ALP, unconjugated bile acid alphaMCA, and TG were
      observed (all P < 0.05). In conclusion, swertianlarin significantly up-regulates
      hepatic bile acid detoxification enzymes and efflux transporters in rats, which
      can increase the water solubility of hydrophobic bile acids and elimination of
      conjugated bile acids. 

PMID- 25755706
TI  - Dynamic properties of the segmentation clock mediated by microRNA.
AB  - Somites are embryonic precursors that give rise to the axial skeleton and
      skeletal muscles and form the segmental vertebrate body plan. Somitogenesis is
      controlled by the "segmentation clock", which contains multiple oscillator genes
      that must be tightly regulated at both the transcriptional and post
      transcriptional levels for proper clock function. However, how the segmentation
      clock governs the formation of the somites at post-transcriptional level, remains
      unclear. In this work, we develop an integrated model with three modules for the
      segmentation clock and explore the mechanism for somite segmentation based on the
      dynamics of the network. By numerical simulations, we find that the amplitude and
      period of the somite segmentation clock are sensitive to Notch activity, which is
      fine-tuned by Lunatic fringe (Lfng) and microRNA (miRNA), and Lfng and miRNA are
      essential for forming the proper segmentation during somitogenesis. Moreover,
      miRNA is found to have a crucial role in minimizing the fluctuation period and
      amplitude to maintain coherent oscillation. Introduction of stochasticity in the
      model enables us to explain the available experimental data with dampening of
      oscillations. These findings uncover a fresh mechanism for regulation of the
      segmentation clock at a post-transcriptional level and provide important insights
      into how the relatively subtle effects of miRNAs on target genes can have broad
      effects in developmental situations that have critical requirements for tight
      posttranscriptional regulation. 

PMID- 25755707
TI  - Development of synthetic of peptide-functionalized liposome for enhanced targeted
      ovarian carcinoma therapy.
AB  - In this study, we report an active targeting liposomal formulation directed by a
      novel peptide (T7) that specifically binds to the transferrin receptor (TfR)
      overexpressed on ovarian carcinoma cells. The objectives of this study were to
      evaluate the in vitro and in vivo tumor drug targeting delivery of T7-anchored
      liposomes on A2780 cells. T7 conjugated to the distal end of DSPE-PEG2000
      maleimide was incorporated into the liposomes via a post-insertion method, the
      liposome could keep stability in 50% FBS for more than 24 h. The uptake
      efficiency of T7-LP was 3.7 times higher than that of LP on A2780 cells. The anti
      proliferative activity of T7-LP-PTX against A2780 cells was much stronger
      compared to that of LP-PTX and free PTX, respectively. The homing specificity and
      anticancer efficacy of T7-LP-PTX were also evaluated on the tumor spheroids,
      which revealed that T7-LP-PTX was more efficaciously internalized into tumor
      cells than LP. Compared to LP, T7-LP-PTX showed the highest accumulation
      capability into tumor spheroids, and the greatest tumor growth inhibitory effect
      in vitro. In the in vivo study, the T7-LP-PTX showed the best inhibition effect
      of the tumor growth for the A2780-bearing mice and tumor accumulation. In brief,
      the T7-LP may be an efficient targeting drug delivery system for ovarian
      carcinoma.

PMID- 25755708
TI  - Delayed cardioprotection by sevoflurane preconditioning: a novel mechanism via
      inhibiting Beclin 1-mediated autophagic cell death in cardiac myocytes exposed to
      hypoxia/reoxygenation injury.
AB  - Sevoflurane preconditioning has shown to exert delayed caridioprotection against
      subsequent ischemia and reperfusion injury, but the mechanisms underlying is
      unclear. Inhibition of autophagy by 3-methyladenine (3-MA) or knockdown of Beclin
      1 leads to enhanced cardiac myocyte survival. Our study aimed to test whether
      sevoflurane preconditioning provides a second window of anesthetic
      preconditioning (SWOP) via inhibit Beclin 1-mediated autophagic cell death. H9c2
      rat cardiomyocytes were randomly divided into five groups: Control (CON) group;
      hypoxia/reoxygenation (H/R) group, rat cardiomyocytes was exposed in the airtight
      container for 2 h followed by 1 h of reoxgenation; SWOP group, rat cardiomyocytes
      was exposed to 1 h of 2.5% sevoflurane 24 h before H/R; Autophagic inhibitors, 3
      methyladenine (3-MA, 10 mM) was added to culture medium 15 min before sevoflurane
      exposure (3-MA+SWOP group) or cells were treated by 3-MA alone (3-MA group). The
      cell proliferation was significantly increased in SWOP group (79.49 +/- 1.37%, P
      < 0.05) when compared to H/R group (62.2 +/- 6.49%, P < 0.05). 3-MA administered
      before SWOP significantly attenuated the H/R induced autophagy and cell death.
      H/R injury up-regulated the expression of LC3-II and Beclin 1 proteins (342 +/-
      66% and 163 +/- 18%, respectively, P < 0.05) compared to the CON group (100%),
      which were increased in SWOP group (202 +/- 77% and 128 +/- 8%, respectively, P <
      0.05). The expression of LC3-II and Beclin 1 proteins was decreased in 3-MA group
      (110 +/- 28% and 97 +/- 6%, respectively) and 3-MA+SWOP group (93 +/- 7% and 98
      +/- 6%, respectively) compared with H/R group, but Bcl-2 was upregulated in 3-MA
      group (158 +/- 4%) and 3-MA+SWOP group (156 +/- 5%) compared to H/R group (103 +/
      7%). In conclusion, sevoflurane preconditioning confers delayed cardioprotection
      via inhibition Beclin 1-mediated autophagic cell death in cardiac myocytes 24 h
      before exposed to H/R injury. 

PMID- 25755709
TI  - Fentanyl inhibits proliferation and invasion of colorectal cancer via beta
      catenin.
AB  - BACKGROUND AND AIM: Fentanyl is widely used for relieving pain and narcotizing in
      cancer patients. However, there are few published reports regarding the effects
      of fentanyl on tumor control and treatment. Here we investigated the effects of
      fentanyl on tumor growth and cell invasion in the human colorectal carcinoma
      (HCT116) cells. METHODS: Nude mice xenografts of HCT116 cells were established to
      assess the inhibition effect on tumor growth by fentanyl. MTT and Transwell were
      employed to determine the cell survival rate and cell invasion, respectively.
      MicroRNAs and mRNAs expression were quantified by real-time PCR. beta-catenin and
      matrix metalloproteinases (MMP-2 and MMP-9) expression were assayed by western
      blotting. beta-Catenin-specific small interfering RNA (Si-beta-catenin) and miR
      182 mimics were transfected in cells to investigate the mechanism underlying the
      effects of fentanyl on the colorectal tumor and HCT116 cells. RESULTS: Treatment
      with fentanyl inhibited the tumor growth and HCT116 cells invasion. Fentanyl also
      downregulated the expression of beta-catenin and miR-182 in both xenograft tumors
      and HCT116 cells, and decreased the protein level of MMP-9 in HCT116 cells.
      Downregulation of beta-Catenin resulted in the decrease of miR-182 expression in
      colorectal cells. In addition, the overexpression of miR-182 reversed the effect
      of fentanyl on MMP-9 expression and cell invasion of HCT116 cells. CONCLUSIONS:
      The current study demonstrated that the inhibition of tumor growth and cell
      invasion in colorectal cancer by fentanyl is probably due to downregulation of
      miR-182 and MMP-9 expression by beta-catenin.

PMID- 25755710
TI  - Boswellic acid attenuates asthma phenotypes by downregulation of GATA3 via pSTAT6
      inhibition in a murine model of asthma.
AB  - Asthma is a serious global health problem characterised by airway inflammation,
      airway epithelial wall shedding, enhanced mucus production, increased IgE levels
      and airway hyperresponsiveness. The pathophysiology of asthma is mediated by Th2
      cells which produce Th2 cytokines like interleukin-4, interleukin-5, interleukin
      13 and interleukin-9. The differentiation of Th2 cells is induced by the
      transcription factor GATA3 which is activated by pSTAT6 via IL-4 signalling. To
      investigate the anti-asthmatic potential of Boswellic acid, as well as the
      underlying mechanism involved, we studied its anti-asthmatic potential in a
      murine model of asthma. In this study, BALB/c mice were systemically sensitized
      by ovalbumin (OVA) followed by aerosol allergen challenges. We investigated the
      effect of Boswellic acid on airway hyperresponsiveness, inflammatory cell
      infiltration, Th2 cytokine and OVA-specific IgE production in a mouse model of
      asthma. We found that Boswellic acid treated groups suppressed allergic airway
      inflammation, AHR, OVA-specific IgE and Th2 cytokines secretion. It also
      suppressed the expression of pSTAT6 and GATA3 in a dose dependent manner. Our
      data suggest that the mechanism by which Boswellic acid effectively treats asthma
      is based on reductions of Th2 cytokines via inhibition of pSTAT6 and GATA-3
      expression. 

PMID- 25755711
TI  - Overexpression of ROCK1 and ROCK2 inhibits human laryngeal squamous cell
      carcinoma.
AB  - Rho-associated coiled-coil containing protein kinase (ROCK) over-expression has
      been implicated in the progression of many tumor types. The aim of this study was
      to explore the roles of ROCK1 and ROCK2 in human laryngeal squamous cell
      carcinoma (LSCC). ROCK1 and ROCK2 expression levels were examined in 50 cases of
      human LSCC samples by immunohistochemistry. Effects of ROCK1 and ROCK2 on LSCC
      cell proliferation and motility were investigated in the presence of the ROCK
      inhibitor Y-27632. The results showed that ROCK1 expression was positively
      correlated with tumor size and lymph node metastasis (P < 0.05); ROCK2 positively
      correlated with tumor size (P < 0.05). Inhibition of ROCK1 and ROCK2 by Y-27632
      significantly inhibits proliferation, migration, and invasion of LSCC cells. Our
      data indicate that expression of ROCK1 and ROCK2 are closely associated with
      tumor growth and lymph node metastasis of LSCC. Thus, these two ROCK isoforms may
      be useful as molecular makers for LSCC diagnosis and may be useful therapeutic
      targets as well. 

PMID- 25755712
TI  - Sequential treatment with betulinic acid followed by 5-fluorouracil shows
      synergistic cytotoxic activity in ovarian cancer cells.
AB  - Betulinic acid selectively inhibits the growth of ovarian carcinoma cell lines
      without affecting the normal cells. In the present study, the effect of 5
      fluorouracil (5-FU) and betulinic acid (BA) combination on ovarian carcinoma
      cells was studied. The results demonstrated that ovarian carcinoma cells on
      concurrent or 5-FU followed by BA treatment show increased Sub-G1 cell
      population, increased rate of cell apoptosis and morphological changes in
      mitochondrial membrane. In OVCAR 432 cells treatment with sequential combination
      of 5-FU and BA increased the Sub-G1 cell population to 51.3% and growth
      inhibition rate of > 72%. However, exposure to BA before 5-FU treatment caused a
      decrease in rate of inhibition to < 35%. Treatment with combination of 5 MUM of 5
      FU and 1 MUM of BA for 48 h, led to an induction of apoptosis in 79.7% and
      induced morphological changes in OVCAR 432 cells. The Western blot results showed
      high concentration of cytochrome c in the cell cytosol after 24 h of 5-FU and BA
      combination treatment. Treatment of BA-responsive RMS-13 cells with 5-FU and BA
      combination resulted in inhibition of GLI1, GLI2, PTCH1, and IGF2 genes. In
      addition, we found a significant reduction in hedgehog activity of RMS-13 cells
      after 5-FU and BA combination treatment by means of a hedgehog-responsive
      reporter assay. Therefore, 5-FU and BA combination can be a promising regimen for
      the treatment of ovarian carcinoma. 

PMID- 25755713
TI  - Primary intracranial Ewing's sarcoma with unusual features.
AB  - Pediatric primary "small round blue cell" tumors in the CNS represent several
      entities, some more common than others. Ewing sarcoma/peripheral primitive
      neuroectodermal tumor (ES/pPNET) is rare and must be distinguished from other
      tumors such as medulloblastoma [1, 2], atypical rhabdoid/teratoid tumor,
      ependymomal tumors, metastatic sarcomas, hematologic malignancies, and other
      mimics. Although therapy for ES/pPNET is effective, it brings severe side
      effects, including cardiac toxicity, making correct recognition important [3]. As
      small blue cell tumors look similar, diagnosis often depends on special stains,
      immunohistochemistry, and molecular techniques. While the combination of
      membranous immunohistochemical reactivity for CD99 with cytoplasmic glycogen
      provides effective screening, demonstration of characteristic translocations of
      EWSR1 (chromosome 22) or FUS (chromosome 16) by fluorescent in situ hybridization
      (FISH) can confirm the diagnosis. We are reporting three primary ES/pPNET of the
      CNS, two of which occurred in children. While the adult case demonstrates the
      classic histopathology, the two pediatric cases have histopathology that
      significantly deviates from the usual. One is suggestive of a primary sarcoma,
      and the other mimics an ependymoma, but all three cases are confirmed with FISH.
      These observations suggest that primary ES in the CNS may have histology
      different from the classic morphology and a high index of suspicion should be
      maintained in order to make the correct diagnosis. A search of the literature
      suggests that these tumors are most frequently seen in children and young adults.
      Imaging often shows a supratentorial enhancing mass that touches the
      leptomeninges. Survival over three years is good but long term prognosis is
      unknown [3, 4]. 

PMID- 25755714
TI  - Immunohistochemical algorithm alone is not enough for predicting the outcome of
      patients with diffuse large B-cell lymphoma treated with R-CHOP.
AB  - Gene expression profiling (GEP), which can divide DLBCL into three groups, is
      impractical to perform routinely. Although algorithms based on
      immunohistochemistry (IHC) have been proposed as a surrogate for GEP analysis,
      the power of them has diminished since rituximab added to the chemotherapy. We
      assessed the prognostic value of four conventional algorithms and the genes in
      each and out of algorithm by IHC and fluorescence in situ hybridization in DLBCL
      patients receiving immunochemotherapy. The results showed that neither single
      protein within algorithms nor the IHC algorithms themselves had strong prognostic
      power. Using MYC aberrations (MA) either on the genetic or protein levels, we
      established a new algorithm called MA that could divide patients into distinct
      prognostic groups. Patients of MA had much shorter overall survival (OS) and
      progression-free survival (PFS) than non-MA (2-year OS: 56.9% vs. 98.7%; 2-year
      PFS: 26.8% vs. 86.9%; P < 0.0001 for both). In conclusions, using additional
      prognostic markers not associated with cell of origin may accurately predict
      outcomes of DLBCL. Studies with larger samples should be performed to confirm our
      algorithm and optimize the prognostic system of DLBCL. 

PMID- 25755715
TI  - Reduction behavior induced by HL010183, a metformin derivative against the growth
      of cutaneous squamous cell carcinoma.
AB  - Metformin is a biguanide widely prescribed as a first-line antidiabetic drug in
      type 2 diabetes mellitus patients. Animal and cellular studies support that
      metformin has a strong anti-proliferative effect on various cancers. Herein, we
      report that metformin derivative, HL010183 significantly inhibited human
      epidermoid A431 tumor xenograft growth in nu/nu mice, which in turn is associated
      with a significant reduction in proliferative biomarkers PCNA and cyclins D1/B1.
      Enhanced apoptotic cell death and an increase in Bax: Bcl2 ratio supported the
      tumor growth reduction. The mechanism of the drug effects appears to be dependent
      on the inhibition of nuclear factor kappa B (NFkB) and mTOR signaling pathways.
      Reduced enhancement of NFkB transcriptional target proteins, iNOS/COX-2 together
      with decreased phosphorylation of NFkB inhibitory protein IKBa were also
      observed. Further, AKT signaling activation was evaluated by the reduced
      phosphorylation at Ser473. In addition, a concomitant decrease in mTOR signaling
      pathway was also estimated from the reduced phosphorylation at mTOR regulatory
      proteins p70S6K and 4E-BP-1. Along with this, decreased phosphorylation of GSK3b,
      which is carried out by AKT kinases was also observed. Overall results suggested
      that HL010183 interrupt SCC growth via NFkB and mTOR signaling pathways. 

PMID- 25755716
TI  - Shikonin protects chondrocytes from interleukin-1beta-induced apoptosis by
      regulating PI3K/Akt signaling pathway.
AB  - Chondrocyte apoptosis is mostly responsible for the development and progression
      of osteoarthritis. IL-1beta is generally served as an agent that induces
      chondrocyte apoptosis. Shikonin exerts its anti-inflammatory effect on cartilage
      protection in vivo. We aimed to explore the protective effect of shikonin on
      interleukin-1beta (IL-1beta)-induced chondrocyte apoptosis and the potential
      molecular mechanisms. Chondrocytes were isolated from the joints of newborn
      Sprague-Dawley rats. The MTT assay and LDH cell death assay were used to
      determine the cell viability and chondrocyte apoptosis was detected by Annexin
      V/PI staining and nucleosomal degradation. The contents of phosphorylated-PI3K (p
      PI3k), phosphorylated-Akt (p-Akt), Bcl-2, Bax, and cytochrome c were detected by
      Western blotting. A quantitative colorimetric assay was used to detect the
      caspase-3 activity. Our results showed that pretreatment with shikonin (4 MUM)
      inhibited cytotoxicity and apoptosis induced by IL-1beta (10 ng/ml) in
      chondrocytes. Shikonin pretreatment also decreased the activity of IL-1beta that
      decreased Bcl-2 expression and levels of p-PI3K and p-Akt, and increased Bax
      expression, cytochrome c release, and caspase-3 activation. It also reversed the
      activity of IL-1beta that promoted the synthesis of matrix metalloproteinase-13
      and inhibited the expression of tissue inhibitor of metalloproteinase-1
      expression, with the net effect of suppressing extracellular matrix degradation.
      These data suggested that shikonin may protect chondrocytes from apoptosis
      induced by IL-1beta through the PI3K/Akt signaling pathway, by deactivating
      caspase-3. 

PMID- 25755717
TI  - RNA interference targeting CD147 inhibits the proliferation, invasiveness, and
      metastatic activity of thyroid carcinoma cells by down-regulating glycolysis.
AB  - A high rate of glycolytic flux, even in the presence of oxygen, is a key
      metabolic hallmark of cancer cells. Lactate, the end product of glycolysis,
      decreases the extracellular pH and contributes to the proliferation, invasiveness
      and metastasis of tumor cells. CD147 play a crucial role in tumorigenicity,
      invasion and metastasis; and CD147 also interacts strongly and specifically with
      monocarboxylate transporter1 (MCT1) that mediates the transport of lactate. The
      objective of this study was to determine whether CD147 is involved, via its
      association with MCT1 to transport lactate, in glycolysis, contributing to the
      progression of thyroid carcinoma. The expression levels of CD147 in surgical
      specimens of normal thyroid, nodular goiter (NG), well-differentiated thyroid
      carcinoma (WDTC), and undifferentiated thyroid carcinoma (UDTC) were determined
      using immunohistochemical techniques. The effects of CD147 silencing on cell
      proliferation, invasiveness, metastasis, co-localization with MCT1, glycolysis
      rate and extracellular pH of thyroid cancer cells (WRO and FRO cell lines) were
      measured after CD147 was knocked-down using siRNA targeting CD147.
      Immunohistochemical analysis of thyroid carcinoma (TC) tissues revealed
      significant increases in signal for CD147 compared with normal tissue or NG,
      while UDTC expressed remarkably higher levels of CD147 compared with WDTC.
      Furthermore, silencing of CD147 in TC cells clearly abrogated the expression of
      MCT1 and its co-localization with CD147 and dramatically decreased both the
      glycolysis rate and extracellular pH. Thus, cell proliferation, invasiveness, and
      metastasis were all significantly decreased by siRNA. These results demonstrate
      in vitro that the expression of CD147 correlates with the degree of
      dedifferentiation of thyroid cancer, and show that CD147 interacts with MCT1 to
      regulate tumor cell glycolysis, resulting in the progression of thyroid
      carcinoma. 

PMID- 25755718
TI  - miR-1179 promotes cell invasion through SLIT2/ROBO1 axis in esophageal squamous
      cell carcinoma.
AB  - MiR-1179, a new identified miRNA highly associated with metastasis of colorectal
      cancer which was never reported in esophageal squamous cell carcinoma (ESCC).
      Here we measured the expression levels of miR-1179 and the candidate target gene
      in tissues from 40 patients with ESCC. Transwell, Dual-luciferase reporter assay
      and immunocytochemistry assay were employed to detect the function role of miR
      1179 in vitro. We found that miR-1179 was up-regulated in human ESCC tumor
      tissues. Bioinformatics analysis indicated that SLIT2 acting as a new potential
      target of miR-1179 which was confirmed by luciferase reporter assay. Down
      regulation of miR-1179 suppressed cell invasion in vitro with an increasing level
      of SLIT2 and ROBO1, besides, the up-regulation of SLIT2 decreased cell invasion
      through ROBO1. Taken together, these findings will shed light the role to
      mechanism of miR-1179 in regulating cell invasion via SLIT2/ROBO1 axis. 

PMID- 25755719
TI  - Decreased expression of TFPI-2 correlated with increased expression of CD133 in
      cholangiocarcinoma.
AB  - BACKGROUND: Recent findings suggest decreasing TFPI-2 expression plays a
      significant role in inhibiting cell migration and tumor invasion. The
      clinicopathological significance of the expression of TFPI-2 and its possible
      correlation with the expression of CD133 in cholangiocarcinoma remains to be
      solved. METHODS: We investigated if TFPI-2 was involved in the
      clinicopathological significance of cholangiocarcinoma. An immunohistochemical
      method was used to detect 218 cases of cholangiocarcinoma, 30 para-neoplastic and
      20 normal bile ducts for their expression status of TFPI-2 and CD133, and then
      the results were analyzed with the patient's age, sex, tumor site and the
      histological grade, clinical stage as well as overall mean survival time.
      RESULTS: Compared with the para-neoplastic and normal cholangiocytes, the
      expression of TFPI-2 was obviously decreased while the expression of CD133 in
      carcinoma cells was increased. Carcinomas with low expression of TFPI-2 were
      significantly corresponding to the tumor site (P = 0.006), size (P = 0.005),
      histological grade (P = 0.0001) and clinical stage (P = 0.0001), but not to the
      age (P = 0.066) and sex (P = 0.411), respectively. By Kaplan-Meier survival
      analysis, the low expression of TFPI-2 was significantly correlative with the
      overall survival time (P = 0.0001). Further, the expression of TFPI-2 was found
      inversely correlative with the expression of CD133 (g = -0.3876, P < 0.0001).
      CONCLUSIONS: Our finding suggests that the decreased expression of TFPI-2 may
      play an important role in the carcinogenesis and progression, and may become a
      new adjunct marker in the diagnosis and prognosis in cholangiocarcinoma. The
      expression of TFPI-2 may be inversely correlative with the expression of CD133.

PMID- 25755720
TI  - MicroRNA-338-3p inhibits cell proliferation in hepatocellular carcinoma by target
      forkhead box P4 (FOXP4).
AB  - MicroRNAs (miRNAs) are a class of small, non-coding RNAs, which have demonstrated
      to important gene regulators, and have critical roles in diverse biological
      processes including cancer cell proliferation. Previous studies suggested
      microRNA-338-3p (miR-338-3p) was down-regulated and play tumor suppressor roles
      in gastric cancer, colorectal carcinoma and lung cancer. However, the role of miR
      338-3p in hepatocellular carcinoma (HCC) is still unclear. In this study, we
      analyzed the expression of miR-338-3p in HCC tissues and HCC cell lines. We find
      that miR-338-3p was downregulated in HCC tissues and cell lines. Then functional
      studies demonstrate ectopic miR-338-3p expression significantly suppressed the in
      vitro proliferation and colony formation of HCC cells and cause to cell cycle
      arrest. Using bio-informatic method and report assay we identified a novel miR
      338-3p target, FOXP4 in HCC cells. Furthermore, knockdown of FOXP4 have the
      similar effects in HCC corrected with miR-338-3p. These findings suggest that miR
      338-3p regulates survival of HCC cells partially through the downregulation of
      FOXP4. Therefore, targeting with the miR-338-3p/FOXP4 axis might serve as a novel
      therapeutic application to treat HCC patients. 

PMID- 25755721
TI  - Increased expression of HMGB3: a novel independent prognostic marker of worse
      outcome in patients with esophageal squamous cell carcinoma.
AB  - HMGB3, an X-linked member of the high-mobility group (HMG) superfamily of HMG
      proteins, has been shown to affect numerous tumorigenic progression. However, the
      expression and the prognostic role of HMGB3 in esophageal squamous cell carcinoma
      (ESCC) remained unknown. In this study, we examined the HMGB3 expression in ESCC
      tissues and adjacent nontumorous tissues by qRT-PCR and immuohistochemistry.
      Statistical analyses were applied to test for prognostic and diagnostic
      associations. The mRNA levels of HMGB3 were found to be significantly higher in
      tumorous tissues than in the adjacent normal tissues. We found that the HMGB3
      expression was higher in tumorous tissues than in the adjacent non-tumorous
      tissues by immunohistochemical analysis of paired tissue specimens (P < 0.001).
      Moreover, there was a significant correlation between HMGB3 expression and gender
      (P = 0.037), clinical stage (P = 0.038), T classification (P = 0.013) and N
      classification (P = 0.017). Patients with higher HMGB3 expression had shorter
      overall survival than those with lower HMGB3 expression. Multivariate Cox
      analysis indicated that HMGB3 expression is an independent prognostic factor for
      overall survival (HR = 0.591, 95% CI = 0.379-0.793, P = 0.039). In summary, these
      findings demonstrate that HMBG3 may be a potential molecular marker for
      predicting the prognosis of ESCC patients. 

PMID- 25755722
TI  - SIRT3 protects endothelial cells from high glucose-induced cytotoxicity.
AB  - Diabetes is a frequent and increasing public health problem with a large economic
      burden in modern society. Endothelial cells dysfunction was involved in the
      development of diabetes-associated diseases. Sirtuins are a conserved family of
      NAD-dependent deacetylases. However, the role of sirtuins in diabetes-associated
      endothelial cell dysfunction was relatively unknown. In this study, we focus on
      the intrinsic link between SIRT3, a mitochondrial sirtuin, and high glucose
      induced endothelial cells dysfunction. We showed that loss of SIRT3 expression
      was associated with decreased viability in endothelial cells from diabetes
      patients. Knockdown of SIRT3 decreased viability of endothelia cells exposed to
      high glucose condition. Further, mechanistic study showed that SIRT3 repression
      results in SOD2 acetylation, leading to SOD2 inactivation, which enhanced high
      glucose-induced oxidative stress in endothelial cells. Our data suggested that
      SIRT3 protects endothelial cells from high glucose-induced cytotoxicity. Our
      findings are considered a significant step toward a better understanding of
      diabetes-associated vascular diseases. 

PMID- 25755723
TI  - RNA interference targeting enhancer of polycomb1 exerts anti-tumor effects in
      lung cancer.
AB  - BACKGROUND AND AIM: Lung cancer is one of leading malignant tumor worldwide with
      a high mortality rate. A new therapy target, enhancer of polycomb1 (EPC1) knocked
      down by short hairpin RNA (shRNA) interference technology, for lung cancer was
      established to investigate its effects on lung cancer in present study. METHODS:
      RNA interference technology was applied to down-regulate the expression of EPC1
      by specific-shRNA with lentivirus vector in neoplastic human alveolar basal
      epithelial cells (A549 cells). The survival rate and apoptosis were respectively
      measured by MTT and Flow Cytometry to evaluate the effects of shRNA EPC1 on
      cells. Mice xenografts of HCT116 cells with shRNA EPC1 were also established to
      assess the effect on tumor growth. The levels of AKT and p65 were detected by
      western blotting. RESULTS: The down-regulation of EPC1 by specific-shRNA with
      lentivirus vector was significantly decreased the survival rate and apoptosis of
      A549 cells, and the tumors in EPC1 shRNA transfection group had a significant
      lower size and weight compared with the ones with control shRNA. The protein
      expression of p-AKT and p65 was reduced by EPC1 shRNA in both in vitro and in
      vivo experiments. CONCLUSION: Silencing EPC1 by shRNA technology had the
      inhibition effects on cell proliferation and tumor growth in lung cancer, which
      provided a new potential target for treatment of cancers.

PMID- 25755724
TI  - MicroRNA-26a inhibits proliferation by targeting high mobility group AT-hook 1 in
      breast cancer.
AB  - OBJECTIVES: To investigate the crucial role of miR-26a in breast cancer and to
      validate whether miR-26a could regulate proliferation of breast cancer cells by
      targeting high mobility group AT-hook 1 (HMGA1). METHODS: Reverse transcription
      polymerase chain reaction (RT-PCR) was used to quantify the expression levels of
      miR-26a in breast cancer and adjacent non-cancerous breast tissues. MTT, cell
      migration and invasion assay were carried out to characterize the miR-26a
      function. Finally, to validate the target gene of miR-26a, luciferase reporter
      assay was employed, followed by RT-PCR and Western blot confirmation. RESULTS:
      Compared with normal tissues, a significant down-regulation of miR-26a expression
      was observed in breast cancer tissues (P=0.002). miR-26a suppresses MDA-MB-231
      and Mcf-7 breast cancer cell lines proliferation and motility. The luciferase
      activity was significantly decreased after co-transfection with psiCHECK-2/HMGA1
      3'-UTR and miR-26a mimics in comparison with control cells, and qRT-PCR and
      Western blotting analysis found that HMGA1 expression at the mRNA and protein
      levels decreased in the miR-26a mimic-treatment group relative to NC. MTT assay
      showed that down regulation of HMGA1 by siRNA could significantly enhance the
      tumor-suppressive effect of miR-26a (P < 0.05). CONCLUSIONS: The results of the
      present study indicate that miR-26a may be associated with human breast
      carcinogenesis, which inhibits tumor cell proliferation by targeting HMGA1.

PMID- 25755725
TI  - Proinflammatory and prothrombotic status in emphysematous rats exposed to
      intermittent hypoxia.
AB  - OBJECTIVES: To develop an "overlap syndrome (OS)" rat model by intermittent
      hypoxia (IH) exposure on the base of pre-existing emphysema, and to explore
      whether "OS" exposure results in more severe systemic inflammation, and whether
      the inflammation changes levels of coagulant/anticoagulant factors and oxidative
      stress status. METHODS: Sixty Wistar rats were put into 4 groups: Control group;
      IH group, IH exposure; Emphysema group, smoke exposure; Overlap group, smoke
      exposure and IH exposure. We obtained peripheral blood for apoptosis of
      CD3(+)CD4(+), CD3(+)CD8(+) T lymphocytes and neutrophils, and for endothelial
      progenitor cell (EPC) counts. Tumor necrosis factor (TNF)-alpha, interleukin (IL)
      6 and coagulant/anticoagulant factors [antithrombin (AT), fibrinogen (FIB),
      Factor VIII (FVIII) and von Willebrand factor (vWF)] were evaluated. We also
      obtained tissue blocks of lung, liver, pancreas, and right carotid artery for
      pathologic scoring and measurements of liver oxidative stress [superoxide
      dismutase (SOD) activity, catalase (CAT) activity and malondialdehyde (MDA)
      concentration]. RESULTS: The levels of TNF-alpha and IL-6, CD3(+)CD4(+) T
      lymphocyte apoptosis, EPC counts, coagulant factors and MDA are the highest in
      Overlap group, the lowest in Control group, when the levels of neutrophil
      apoptosis, CD3(+)CD8(+) T lymphocyte apoptosis, AT, SOD and CAT are the lowest in
      Overlap group, the highest in Control group (all P values < 0.05). CONCLUSION: In
      model animals, when IH is combined with emphysema, there will be a more severe or
      an "overlapped" systemic/multiple organic inflammation, oxidative stress and
      hyper-coagulability. And the pro-inflammatory and pro-thrombotic status resulted
      from "OS" exposure may elicit a robust EPC mobilization, which needs further
      investigation.

PMID- 25755726
TI  - MicroRNA-130a inhibits cell proliferation, invasion and migration in human breast
      cancer by targeting the RAB5A.
AB  - MiR-130a has been demonstrated to play important roles in many types of cancers.
      Nevertheless, its biological function in breast cancer remains largely unknown.
      In this study, we found that the expression level of miR-130a was down-regulated
      in breast cancer tissues and cells. Overexpression of miR-130a was able to
      inhibit cell proliferation, invasion and migration in MCF7 and MDA-MB-435 cells.
      With the bioinformatics analysis, we further identified that RAB5A was a directly
      target of miR-130a, and its mRNA and protein level was negatively regulated by
      miR-130a. Immunohistochemistry verified RAB5A was upregulated in breast cancer
      tissues. Therefore, the data reported here demonstrate that miR-130a is an
      important tumor suppressor in breast cancer, and imply that miR-130a/RAB5A axis
      have potential as therapeutic targets for breast cancer. 

PMID- 25755727
TI  - Genistein attenuates glucocorticoid-induced bone deleterious effects through
      regulation Eph/ephrin expression in aged mice.
AB  - OBJECTIVE: This study was performed to investigate bone deteriorations and the
      involvement of skeletal Eph/ephrin signaling pathway of GIOP aged mice in
      response to the treatment of genistein. METHODS: The biomarkers in serum and
      urine were measured, tibias were taken for the measurement on gene and protein
      expression and histomorphology analysis, and femurs were taken for the
      measurement on bone Ca and three-dimensional architecture of trabecular bone.
      RESULTS: Genistein showed a greater increase in bone Ca, BMD and significantly
      increased FGF-23 and OCN, reduced TRACP-5b, PTH and CTX in GIOP mice. Genistein
      reversed DXM-induced trabecular deleterious effects and stimulated bone
      remodeling. The treatment of DXM group with genistein significantly elevated the
      ratio of OPG/RANKL. Moreover, genistein administration down-regulated the mRNA
      and protein expression of Eph A2 and ephrin A2 in tibia of the GIOP mice. In
      contrast, the mRNA and protein expression of Eph B4 and ephrin B2 were increased
      in mice treated by DXM with genistein as compared to the DXM single treatment.
      CONCLUSIONS: DXM-induced trabecular bone micro-structure deterioration in aged
      mice was involved in the regulation of the Eph receptors and ephrin ligands.
      Genistein might represent a therapy with bone-forming as well as an anti
      resorptive activity in GIOP mice. The underlying mechanism was mediated, at least
      partially, through regulation Eph/ephrin signaling.

PMID- 25755728
TI  - Expression of eukaryotic initiation factor 4E and 4E binding protein 1 in
      colorectal carcinogenesis.
AB  - Cap dependent translation is mainly regulated at the level of the eukaryotic
      initiation factor 4E (eIF4E), the activity of which is controlled by
      phosphorylation and sequestration by its well established regulator, 4E binding
      protein 1 (4E-BP1). Both eIF4E and 4E-BP1 have been shown to be involved in the
      malignant progression of multiple human cancers, including colorectal cancer.
      However, the data on determining the expression of eIF4E, 4E-BP1 and their
      phosphorylated forms simultaneously in a single patient with colorectal cancer is
      lacking. Therefore the aim of our study was to explore the roles of these factors
      in colorectal carcinogenesis by immunohistostaining colorectal tissues (normal,
      low grade adenoma, high grade adenoma, and adenocarcinoma). Our results showed
      that the expression levels of eIF4E increased steadily as the cancer progressed
      from the case of benign dysplasia to an adenocarcinoma; all the while maintaining
      an unphosphorylated form. On the other hand, total expression levels of 4E-BP1
      increased only in the premalignant state of the disease and decreased (but highly
      phosphorylated or inactivated) or abolished upon malignancy. Taken together, our
      findings suggest that strong correlations exist between the expression of eIF4E
      (not p-eIF4E) and tumor grade providing evidence that eIF4E expression plays a
      pivotal role in the malignant progression of colorectal cancer. Moreover, 4E-BP1
      showed a bi-phasic level of expression during carcinogenesis, which is expressed
      only in hyperplasic or dysplastic tissues as an endogenous tumor suppressor
      molecule. 

PMID- 25755729
TI  - MiR-21 suppresses endothelial progenitor cell proliferation by activating the
      TGFbeta signaling pathway via downregulation of WWP1.
AB  - Endothelial damage is strongly associated with cardiovascular diseases such as
      atherosclerosis. Bone marrow-derived endothelial progenitor cells (EPCs) play an
      important role in the maintenance of endothelial homeostasis and contribute to re
      endothelialization of injured vessels as well as revascularization of ischemic
      tissues. MicroRNAs (miRNAs) have been reported to regulate EPC biological
      functions. In this study, we found that EPCs of atherosclerosis patients and EPCs
      exposed to hypoxia have increased expression of miRNA-21 (miR-21) as well as
      diminished ability to proliferate. MiR-21 knockdown rescued hypoxia-induced
      growth arrest in EPCs. Next, we used a luciferase reporter assay to demonstrate
      that miR-21 downregulates the expression of WW domain-containing protein 1
      (WWP1), a negative regulator of TGFbeta signaling, by directly targeting the 3'
      UTR of WWP1. Finally, miR-21 overexpression or WWP1 knockdown in EPCs
      significantly activates the TGFbeta signaling pathway and inhibits cell
      proliferation. Taken together, our results indicate that miR-21 suppresses EPC
      proliferation by activating the TGFbeta signaling pathway via downregulation of
      WWP1. These findings may help the development of strategies to enhance the
      vitality of EPCs for therapeutic applications. 

PMID- 25755730
TI  - Prognostic value of SATB2 expression in patients with esophageal squamous cell
      carcinoma.
AB  - SATB2, a member of the family of special AT-rich binding proteins, has been shown
      to affect numerous tumorigenesis. However, the role of SATB2 in esophageal
      squamous cell carcinoma (ESCC) remains unclear. In this study, the SATB2
      expression was examined at mRNA and protein levels by quantitative real-time
      reverse transcriptase-polymerase chain reaction (qRT-PCR), Western blotting, and
      immunohistochemistry in ESCC tissues and adjacent non-cancerous tissues.
      Statistical analyses were applied to test the associations between SATB2
      expression, clinicopathologic factors, and prognosis. Western blotting and qRT
      PCR showed that the expression levels of SATB2 mRNA and protein were both
      significantly lower in SATB2 tissues than those in non-cancerous tissues.
      Immunohistochemistry analysis showed that SATB2 expression was significantly
      correlated with clinical stage and Histological differentiation. The results of
      Kaplan-Meier analysis indicated that a low expression level of SATB2 resulted in
      a significantly poor prognosis of ESCC patients. Importantly, multivariate
      analysis showed that low SATB2 expression was an independent prognostic factor
      for ESCC patients. In sum, our data suggest that SATB2 plays an important role in
      ESCC progression, and that decreased expression of SATB2 in tumor tissues could
      be used as a potential prognostic marker for patients with ESCC. 

PMID- 25755731
TI  - PAF receptor antagonist Ginkgolide B inhibits tumourigenesis and angiogenesis in
      colitis-associated cancer.
AB  - Platelet activating factor (PAF), a potent pro-inflammatory phospholipid, has
      been found to trigger tumor growth and angiogenesis through its G-protein coupled
      receptor (PAFR). This study was aimed to investigate the potential role of PAF in
      azoxymethane (AOM)/dextran sulfate sodium (DSS) induced colitis-associated cancer
      (CAC), using PAFR antagonist Ginkgolide B (GKB). We found GKB up-regulated serum
      level of PAF-AH activity. As assessed by disease activity index (DAI),
      histological injury scores, leukocytes infiltration, and expression of pro
      inflammatory cytokines, GKB ameliorated colonic inflammation and decreased tumor
      number and load in mice. GKB also decreased expression of vascular endothelial
      growth factor (VEGF) and microvessel density (MVD) in tumor. These results
      suggest that PAFR antagonist might be a potential therapeutic strategy for CAC. 

PMID- 25755732
TI  - Panax notoginseng saponins promote wound repair of anterior cruciate ligament
      through phosphorylation of PI3K, AKT and ERK.
AB  - Panax notoginseng saponins (PNS) are components derived from Chinese herb panax
      notoginseng and play important roles in the cure of wounds. However, how PNS
      plays this function is still unclear. In this study, we used MTT assay, wound
      healing assay, western blot, quantitative real time PCR and enzyme-linked
      immunosorbent assay to detect the effects of PNS on the proliferation, migration
      and expression of collagen and fibronectin of anterior cruciate ligament (ACL)
      fibroblasts as well as the underlying mechanism. We found that PNS promoted the
      proliferation and migration of ACL fibroblasts and increased the expression
      levels of collagen and fibronectin. Further mechanism study indicates that PNS
      might play its function through the phosphorylation of PI3K, AKT and ERK. This
      study provides a possible mechanism for the function of PNS and lays foundation
      for further study on the function of panax notoginseng. 

PMID- 25755733
TI  - Adiponectin upregulates ABCA1 expression through liver X receptor alpha signaling
      pathway in RAW 264.7 macrophages.
AB  - ATP-binding cassette transporter A1 (ABCA1) plays a crucial role in reverse
      cholesterol transport and anti-atherosclerosis. Liver X receptor alpha (LXRalpha)
      can stimulate cholesterol efflux through ABCA1. It has been well known that
      adiponectin has cardiovascular protection. In this study, we attempted to clarify
      the effect of adiponectin on expression of ABCA1, and explored the role of
      LXRalpha in the regulation of ABCA1 in RAW 264.7 macrophages. Our results showed
      that adiponectin increased ABCA1 expression at both the mRNA and protein levels
      in a dose-dependent and time-dependent manner. Consequently, adiponectin promoted
      cholesterol efflux and decreased cholesterol content in RAW 264.7 macrophages.
      Moreover, adiponectin up-regulated the expression of LXRalpha in a dose-dependent
      and time-dependent manner in RAW 264.7 macrophages. LXRalpha small interfering
      RNA completely abolished the promotion effects of adiponectin. In summary,
      adiponectin up-regulates ABCA1 expression via the LXRalpha pathway in RAW 264.7
      macrophages. This novel insight could prove useful for developing new treatment
      strategies for cardiovascular diseases. 

PMID- 25755734
TI  - Effect of modified Chung-Sim-Youn-Ja-Tang on anti-inflammatory and anti
      lipogenesis in RAW 264.7 and 3T3-L1 cells.
AB  - Jea-Ma-Chung-Sim-Youn-Ja-Tang (JCST), one of herbal formulae, is modified
      prescription base on Chung-Sim-Youn-Ja-Tang (CST) which treats cerebrovascular
      disease for the Tae-Eum-In (TE). This study was designed to determine the anti
      inflammatory and anti-adipogenesis effect of CST and JCST in vitro. CST and JCST
      of various concentrations were added in RAW 264.7 and 3T3-L1 cell. To determine
      the anti-inflammatory and anti-adipogenesis effects of CST and JCST, the PGE2
      production was measured by lipopolysaccharide (LPS) treated RAW 264.7 cell. The
      adipocytes was determined by Oil red O staining, triglyceride (TG) production,
      leptin level and the protein expressions of peroxisome proliferator-activated
      receptor gamma (PPARgamma), CCAAT/enhancer binding proteins alpha (C/EBPalpha)
      and fatty acid binding protein 4 (FABP4) in 3T3-L1 adipocytes. Our results showed
      that treatment with JCST significantly decreased PGE2 production on RAW 264.7
      cell and suppressed adipocyte differentiation, lipid accumulation, TG production,
      leptin contents and the protein expressions of PPARgamma, C/EBPalpha and FABP4 on
      3T3-L1 adipocytes compared to CST without affecting cell viability. In
      conclusions, our results suggest that JCST may be useful to inhibit the effect on
      lipid metabolism compared to CST, and regulates lipogenesis effectively.
      Therefore, our data provides scientific evidence to support the clinical use of
      JCST in the treatment of cerebrovascular diseases such as stroke in the TE. 

PMID- 25755735
TI  - Losartan reduces myocardial interstitial fibrosis in diabetic cardiomyopathy rats
      by inhibiting JAK/STAT signaling pathway.
AB  - PURPOSE: This study was designed to investigate the effect of losartan on the
      myocardial interstitial fibrosis in diabetic cardiomyopathy (DCM) rats. METHODS:
      In this study, a total of 48 male Wister rats (3 groups of 16 animals each) were
      examined, including the control group, DCM group and losartan-treated (DCM + L)
      group. Control group was fed with standard diet (14 KJ/g); DCM group and losartan
      treated (DCM + L) group were both fed with high glucose and fat diet (20 KJ/g).
      Diabetes was induced by streptozotocin (STZ) intraperitoneal injuction (IP, 30
      mg/kg body weight). Rats of DCM + L group were treated with losartan (30 mg/kg
      body weight) daily by oral gavage for 16 weeks. Biochemical, hemodynamic,
      histological and western blotting analyses were performed. RESULTS: Compared with
      DCM rats, the quantity of p-JAK2 and p-STAT3 in myocardium of rats treated with
      losartan was lower, the expression of TGF-beta1 was down-regulate, the content of
      collagen in myocardium decreased, LVSP and +/- dp/dt increased, LVEDP decreased,
      the level of myocardial fibrosis reduced, and heart function improved evidently.
      CONCLUSION: Losartan has a protective effect on heart function against myocardial
      interstitial fibrosis of DCM by inhibiting JAK/STAT signaling pathway and
      lowering the expression of TGF-beta1.

PMID- 25755736
TI  - Hydrogen sulfide improves cardiomyocytes electrical remodeling post
      ischemia/reperfusion injury in rats.
AB  - Hydrogen sulfide (H2S), produced by cystanthionine-gamma-lysase (CSE) in the
      cardiovascular system, is an endogenous gaseous mediator exerting pronounced
      physiological effects as the third gasotransmitter in addition to nitric oxide
      (NO) and carbon monoxide (CO). Accumulating evidence indicated that H2S could
      mediate the cardioprotective effects in myocardial ischemia model. Ventricular
      arrhythmia is the most important risk factor for cardiac mortality and sudden
      death after acute myocardial infarction (AMI). The potential impact of H2S on
      cardiomyocytes electrical remodeling post ischemic insult is not fully explored
      now. Present study investigated the role of H2S on cardiomyocytes electrical
      remodeling in rats with ischemia/reperfusion injury. H2S concentration was
      reduced and arrhythmia score was increased in this model. CSE mRNA level was also
      upregulated in the ischemic myocardium. Exposure to exogenous NaHS reduced the
      action potential duration (APD), inhibited L-type Ca(2+) channels and activated
      K(ATP) channels in cardiomyocytes isolated from ischemic myocardium Exogenous H2S
      application improves electrical remodeling in cardiomyocytes isolated from
      ischemic myocardium. These results indicated that reduced H2S level might be
      linked to ischemia/reperfusion induced arrhythmias.

PMID- 25755737
TI  - Vaspin alleviates dysfunction of endothelial progenitor cells induced by high
      glucose via PI3K/Akt/eNOS pathway.
AB  - Improving the dysfunction of endothelial progenitor cell (EPCs) in patients with
      diabetes mellitus is important for preventing vascular complication. Vaspin, an
      adipocytokine, has the anti-atherogenic properties rely on its positive effect on
      nitric oxide (NO) bioavailability. We hypothesis that vaspin may ameliorate high
      glucose induced dysfunction of EPCs. In rat bone marrow derived EPCs, glucose
      treatment results in a decrease in the proliferation and migration capacity in a
      dose dependent manner. These detrimental effects can be alleviated by vaspin.
      Furthermore, vaspin increased the production of NO and the effect of vaspin on
      EPCs can be diminished partly by the eNOS inhibitor (L-NAME). We assessed total
      eNOS protein expression and Ser(1177)-phospho-eNOS expression and found that
      vaspin not only induced eNOS protein expression but also up regulate the eNOS
      activation. Subsequently, we investigated protein kinase B (Akt) activation in
      the presence and absence of phosphatidylinositol 3-kinase (PI 3-kinase) inhibitor
      (LY-2940002). Vaspin increased total Akt and Ser(473)-phospho-Akt expression and
      these effects can be blocked by LY-2940002. The results of our study indicate a
      novel effect of vaspin to regulate eNOS expression and function in EPCs via a
      PI3K/Akt/eNOS pathway; vaspin may have a protective effect in patients with
      diabetes to prevent the occurrence of vascular complication.

PMID- 25755738
TI  - Downregulation of ring-finger protein 43 in glioma associates with poor
      prognosis.
AB  - Ring-finger protein 43 (RNF43) has been identified as a RING-type E3 ubiquitin
      ligase. The overexpression of RNF43 results in a significant enhancement of cell
      growth, and knockdown of the expression of RNF43 by siRNAs exerts a growth
      suppressing effect. RNF43 has been proposed as a tumor suppressor in colorectal
      cancers. However, its expression significance in glioma has not been well
      studied. In the present study, we found that the decreased expression of RNF43
      was associated with poor prognosis by the Kaplan-Meier survival analysis (P <
      0.001). Importantly, multivariate analysis suggested RN43 as an independent
      predictor of overall survival ([hazard ratio (HR) 0.547, 95% confidence interval
      (95% CI) 0.382-0.784, P = 0.001]). Collectively, our study demonstrated that
      RNF43 could be served as a potential prognostic marker for patients with this
      deadly disease. 

PMID- 25755739
TI  - Effect of ischemia reperfusion on rabbit VX2 cells in a hepatocellular carcinoma
      model.
AB  - BACKGROUND: We established a rabbit VX2 cell liver carcinoma model to evaluate
      effects of ischemia reperfusion (IR) on reactive oxygen species (ROS) development
      and liver cell apoptosis rates. METHODS: Thirty-six rabbits were divided into a
      control (n=6) and a VX2 hepatocellular carcinoma (HCC) model group (n=30), which
      received VX2 cell suspension injections into their livers. From the 30 HCC
      rabbits, 6 rabbits served as control without hepatic ischemia and the rest were
      treated with hepatic artery and portal vein clamps for 60 minutes. At 1 hour, 1
      day, 3 days and 7 days of reperfusion, 6 rabbits were sacrificed and changes of
      catalase (CAT) and super-oxide dismutase (SOD) activities as well as apoptosis
      rates, measured by TUNEL assays, were compared between tumor tissues, normal
      tumor surrounding hepatic tissues and controls. RESULTS: All treated animals
      developed liver tumors. The CAT activity increased in both tissues 1 hour after
      reperfusion (P < 0.05) and dropped to low levels in the hepatocarcinoma cells at
      day 1 after reperfusion (P < 0.01), but increased to higher levels than the
      control on day 3 (P < 0.05). SOD activity decreased significantly in both tissues
      until day 1 after reperfusion and kept low in the hepatocarcinoma cells until day
      7 (P < 0.05). The apoptosis rates after IR increased more in cancer than in
      normal hepatic tissues (P < 0.01). CONCLUSION: Injection of VX2 tumor cell
      suspension into rabbit liver parenchyma achieved good results for creating a
      liver tumor model. IR induced apoptosis of tumor tissue and normal hepatic
      tissues via ROS development.

PMID- 25755740
TI  - HMGB1-induced autophagy in Schwann cells promotes neuroblastoma proliferation.
AB  - Neuroblastoma inflicts mostly on children, and the pathogenesis remains elusive.
      Clinical diagnosis and therapeutic approaches are still on the incipient stage,
      so further understanding of the molecular and cellular mechanisms of the disease
      is necessary. Inflammation has been commonly regarded as a hallmark in
      tumorigenesis and development, and we identified a new inflammatory factor,
      HMGB1, is considerably increased in neuroblastoma. Our study shows that HMGB1
      induces autophagy in Schwann cells through activation of TLR4, and knockdown of
      TLR4 obviates the HMGB1-induced autophagy. The HMGB1-induced autophagy is through
      classical pathway, as deficiency of Beclin 1 deprived autophagy in Schwann cells.
      Coculture of neuroblastoma with Schwann cells pretreated with HMGB1 promoted the
      proliferation of neuroblastoma cells, and if Beclin 1 is knocked down in Schwann
      cells, no promotion effects is observed. Taken together, our study demonstrates
      that HMGB1-induced autophagy in Schwann cells contributes to neuroblastoma cell
      proliferation, thus providing a potential therapeutic approach on neuroblastoma
      development. 

PMID- 25755741
TI  - Clinicopathological findings of focal organizing pneumonia: a retrospective study
      of 37 cases.
AB  - BACKGROUND AND OBJECTIVE: Focal organizing pneumonia (FOP) is an uncommon
      disease. The etiology, and in particular the disease's relationship with
      infection and the incidence of idiopathic FOP, is relatively unknown. The aim of
      this study is to review clinical, radiological and pathological features of
      patients with organizing pneumonia (OP) presenting solitary lesions and to
      analyze possible causes. METHODS: We retrospectively reviewed 37 surgical lung
      biopsy or resection cases of pathologically confirmed FOP over a period of 10
      years. RESULTS: Microscopically, 17 cases showed OP with neutrophilic
      infiltration or abscess, 11 with epithelioid cell granulomas or scattered
      multinucleated giant cells, 2 with greater eosinophilic infiltration, and the
      remaining 7 cases met the diagnostic criteria for pathological cryptogenic OP
      (COP). The 37 cases of FOP included 22 men and 15 women, aged 29-76 years, and 17
      cases had a history of smoking. Cough, fever, sputum, chest or back pain and
      hemoptysis were the main symptoms. Seven cases were asymptomatic. The diameters
      of the lesions ranged from 0.2-6.0 cm (median, 3.0 cm). Fever (9/30), high
      sensitivity C-reactive protein elevation (9/17) and abnormalities in pulmonary
      function test (8/24) existed in focal secondary OP (FSOP) patients, but these
      symptoms were rarely observed in focal COP (FCOP) (0/7, 1/7 and 0/7 cases,
      respectively). However, no statistically significant differences were found
      between the FSOP and FCOP. CONCLUSIONS: Histologically, secondary factors exist
      in the majority of FOP cases. Idiopathic FOP is found in a minority. With respect
      to secondary FOP, acute infection and granulomatous inflammation are the main
      causes. Surgical resection alone appears sufficient for the management of FOP.

PMID- 25755742
TI  - Integrated regulatory mechanisms of miRNAs and targeted genes involved in
      colorectal cancer.
AB  - PURPOSE: CRC (Colorectal cancer) is a lethal cancer for death worldwide and the
      underlying pathological mechanisms for CRC progression remain unclear. We aimed
      to explore the regulatory mechanism of CRC and provide novel biomarkers for CRC
      screening. METHODS: Downloading from GEO (Gene Expression Omnibus) database,
      Microarray data GSE44861 were consisted of 111 colon tissues samples including 55
      from adjacent noncancerous tissues and 56 from tumors tissues. After data pre
      processing, up- and down regulated DEGs (differentially expressed genes) were
      identified using Bayes moderated t-test. Then DIVAD (Database for Annotation,
      Visualization and Integrated Discovery) was recruited to perform functional
      analysis for DEGs. Thereafter, PPI (protein-protein interaction) network was
      constructed by mapping DEGs into STRING (Search Tool for the Retrieval of
      Interacting Genes) database. Further, PPI modules were constructed and the
      protein domains of DEGs in the modules were analyzed. Moreover, miRNA regulatory
      network was established through GSEA (gene set enrichment analysis) method.
      RESULTS: In summary, 96 up- and 212 down-regulated DEGs were identified. Totally,
      ten DEGs with high degrees in the constructed PPI network were selected, in which
      COLL1A1, PTGS2 and ASPN were also identified as crucial genes in PPI modules.
      Furthermore, COLL1A1 was predicted to be targeted by miR-29, while PTGS2 and ASPN
      were both predicted to be regulated by miR-101 and miR-26. CONCLUSION: COL11A1
      might involve in the progression of CRC via being targeted by miR-29, whereas
      PTGS2 and ASPN were both regulated by miR-101 and miR-26. Moreover, ASPN may be
      supposed as a novel biomarker for CRC detection and prevention.

PMID- 25755743
TI  - Exercise preconditioning attenuates pressure overload-induced pathological
      cardiac hypertrophy.
AB  - Pathological cardiac hypertrophy, a common response of the heart to a variety of
      cardiovascular diseases, is typically associated with myocytes remodeling and
      fibrotic replacement, cardiac dysfunction. Exercise preconditioning (EP)
      increases the myocardial mechanical load and enhances tolerance of cardiac
      ischemia-reperfusion injury (IRI), however, is less reported in pathological
      cardiac hypertrophy. To determine the effect of EP in pathological cardiac
      hypertrophy, Male 10-wk-old Sprague-Dawley rats (n=30) were subjected to 4 weeks
      of EP followed by 4-8 weeks of pressure overload (transverse aortic constriction,
      TAC) to induce pathological remodeling. TAC in untrained controls (n=30) led to
      pathological cardiac hypertrophy, depressed systolic function. We observed that
      left ventricular wall thickness in end diastole, heart size, heart weight-to-body
      weight ratio, heart weight-to-tibia length ratio, cross-sectional area of
      cardiomyocytes and the reactivation of fetal genes (atrial natriuretic peptide
      and brain natriuretic peptide) were markedly increased, meanwhile left
      ventricular internal dimension at end-diastole, systolic function were
      significantly decreased by TAC at 4 wks after operation (P < 0.01), all of which
      were effectively inhibited by EP treatment (P < 0.05), but the differences of
      these parameters were decreased at 8 wks after operation. Furthermore, EP
      treatment inhibited degradation of IkappaBalpha, and decreased NF-kappaB p65
      subunit levels in the nuclear fraction, and then reduced IL2 levels in the
      myocardium of rats subject to TAC. EP can effectively attenuate pathological
      cardiac hypertrophic responses induced by TAC possibly through inhibition of
      degradation of IkappaB and blockade of the NF-kappaB signaling pathway in the
      early stage of pathological cardiac hypertrophy. 

PMID- 25755744
TI  - High expression of MAGE-A9 in tumor and stromal cells of non-small cell lung
      cancer was correlated with patient poor survival.
AB  - Melanoma associated antigen-A (MAGE-A) is an oncogene and correlated with tumor
      initiation and development. However the roles of MAGE-A9 in non-small cell lung
      cancer (NSCLC) are still unknown. We investigated MAGE-A9 mRNA expression in 18
      tumor tissues of NSCLC by qRT-PCR and MAGE-A9 protein expression in 213 NSCLC
      samples of tissue arrays by immunohistochemical staining. We assessed the
      relationship between MAGE-A9 expression and clinical parameters. The results
      showed that the high expression of MAGE-A9 protein in NSCLC tumor cells were
      commonly present in squamous cell carcinomas (P = 0.030). It was also related to
      larger tumor diameter, lymph node metastasis and later stage grouping with TNM
      classification (all P < 0.05). Whereas the expression of MAGE-A9 in stromal cells
      was higher in squamous cell carcinomas as well. Cox regression univariate and
      multivariable analysis revealed that MAGE-A9 expression in tumor cells of NSCLC
      (P < 0.001) is an independent prognostic factor in five-year overall survival
      rate. We concluded that the molecular assessment of MAGEA9 could be considered to
      improve prognostic evaluation and to identify eligible patients for potential
      target therapy. 

PMID- 25755745
TI  - Expression of Girdin in primary hepatocellular carcinoma and its effect on cell
      proliferation and invasion.
AB  - Girdin has been proven to play a vital role in the process of proliferation,
      apoptosis, and invasion in various cancer cells, yet the underlying molecular
      mechanism in primary hepatocellular carcinoma (HCC) has not yet been clarified.
      Thereafter, we performed immunohistochemistry to detect the expression of Girdin
      in 40 primary HCC tissues and 30 matched adjacent tissues using hepatic carcinoma
      tissue microarray. Our data showed that the positive expression rate of Girdin in
      hepatocellular carcinoma tissues was 67.5%, higher than that found in adjacent
      tissues of 16.7% (P < 0.05). It closely correlates to tumor size, T stage, TNM
      stage and Edmondson-Steiner stage (P < 0.05) of HCC patients. After specific
      small interfering RNA of Girdin was transfected into HepG2 and Huh7.5.1 cells,
      the proliferation and invasion ability of tumor cells were significantly
      inhibited. In summary, we suggest that the oncogenic role of Girdin could provide
      new molecular target for the treatment of HCC. 

PMID- 25755746
TI  - Expression of cancer stem cell markers and epithelial-mesenchymal transition
      related factors in anaplastic thyroid carcinoma.
AB  - BACKGROUND: Anaplastic thyroid carcinoma (ATC) is an undifferentiated tumor of
      the thyroid that has poor prognosis owing to its aggressive behavior and
      resistance to current treatments. We hypothesized that the stem cell properties
      induced by the epithelial-mesenchymal transition (EMT) was one of reasons for the
      dismal outcome of ATC. MATERIALS AND METHODS: Paraffin blocks and slides of 17
      ATC cases were retrieved. We also collected 60 cases of papillary thyroid
      carcinoma (PTC) for comparison. We used immunohistochemistry to examine the
      expression of multiple markers of cancer stem cells and EMT-activating
      transcriptional factors. RESULTS: Majority of ATC cases showed loss of epithelial
      (E)-cadherin expression (15/17); however, all PTC cases (60/60) retained E
      cadherin expression. EMT-activating transcription factors, such as snail and
      slug, were more frequently expressed in ATC than PTC cases (35.3% versus 6.7%,
      76.5% versus 5%, respectively). Cancer stem cell markers such as CD133 and nestin
      were more highly expressed in ATC than PTC (52.9% versus 5%, 52.9% versus 0%,
      respectively). CONCLUSION: We found that the expression of EMT-related factors
      and stem cell markers was higher in ATC than PTC. We therefore conclude that
      stemness induced by EMT plays an important role in the pathogenesis of ATC.

PMID- 25755747
TI  - Epidemiological and pathobiological profiles of Clostridium perfringens
      infections: review of consecutive series of 33 cases over a 13-year period.
AB  - BACKGROUND: Although Clostridium perfringens (C. perfringens) is well known as
      the causative agent of several forms of enteric disease, precise epidemiological
      and pathobiological aspects are still unknown. METHODS: We retrospectively
      reviewed the culture results of samples collected in our hospital from 2001
      through 2013. In addition, for the detection and toxinogenic typing of C.
      perfringens, polymerase-chain-reaction amplification (PCR)-based rapid analysis
      was performed in 6 cases using DNA extracted from paraffin-embedded tissues.
      RESULTS: A total of 35 samples from 33 cases were positive for C. perfringens,
      representing an incidence of 0.017% (35/205, 114). Among 33 patients, 21 patients
      manifested sepsis and 7 patients had bacteremia. One of the septic cases was
      complicated by fatal intravascular hemolysis and thus, the prevalence was
      estimated at 3.0% among C. perfringens infections (1/33). The direct causative
      disease or state for C. perfringens infection was identified in 18 patients:
      surgery or intervention for cancers, 8 patients; chemotherapy for cancer, 2
      patients; surgery or intervention for non-neoplastic disease, 6 patients; liver
      cirrhosis, 3 patients, etc. PCR-based toxinogenic typing of C. perfringens
      detected the alpha-toxin gene only in tissue from a patient who died of massive
      hemolysis; none of the toxin genes could be amplified in the other 5 cases
      examined. CONCLUSIONS: The prevalence of overt C. perfringens infection is low,
      but upon detection, infected patients should be carefully monitored for fatal
      acute hemolysis caused by type A C. perfringens. Furthermore, PCR-based rapid
      detection of C. perfringens and toxinogenic typing by archival pathological
      material is applicable as a diagnostic tool.

PMID- 25755748
TI  - Wnt signaling pathway participates in valproic acid-induced neuronal
      differentiation of neural stem cells.
AB  - Neural stem cells (NSCs) are multipotent cells that have the capacity for
      differentiation into the major cell types of the nervous system, i.e. neurons,
      astrocytes and oligodendrocytes. Valproic acid (VPA) is a widely prescribed drug
      for seizures and bipolar disorder in clinic. Previously, a number of researches
      have been shown that VPA has differential effects on growth, proliferation and
      differentiation in many types of cells. However, whether VPA can induce NSCs from
      embryonic cerebral cortex differentiate into neurons and its possible molecular
      mechanism is also not clear. Wnt signaling is implicated in the control of cell
      growth and differentiation during CNS development in animal model, but its action
      at the cellular level has been poorly understood. In this experiment, we examined
      neuronal differentiation of NSCs induced by VPA culture media using vitro
      immunochemistry assay. The neuronal differentiation of NSCs was examined after
      treated with 0.75 mM VPA for three, seven and ten days. RT-PCR assay was employed
      to examine the level of Wnt-3alpha and beta-catenin. The results indicated that
      there were more beta-tublin III positive cells in NSCs treated with VPA medium
      compared to the control group. The expression of Wnt-3alpha and beta-catenin in
      NSCs treated with VPA medium was significantly greater compared to that of
      control media. In conclusion, these findings indicated that VPA could induce
      neuronal differentiation of NSCs by activating Wnt signal pathway. 

PMID- 25755749
TI  - Effects of sleep deprivation on behaviors and abnormal hippocampal BDNF/miR-10B
      expression in rats with chronic stress depression.
AB  - Being sleep-deprived can relieve the depressed emotions in rats, but the
      underlying mechanisms remain unknown. In this study, male rats were divided into
      3 groups: normal control (NC), chronicunpredictable stress (CUPS) and sleep
      deprived (SD). All of the groups were examined using the sucrose consumption test
      and the open field test. The sucrose consumption test and the open field test
      were performed for all three groups. The BDNF and miR-10B expressions were
      examined using real-time PCR and the level of BNDF was discovered by western
      blotting. In the sucrose consumption test and the open field test, the CUPS rats
      consumed less sucrose and got fewer score than the NC rats, however the SD rats
      consumed significantly more sucrose and received higher scores than the CUPS
      rats. Both the expression of BNDF and the protein levels in the CUPS group was
      significantly lower than in the NC group. Also, the CUPS group also showed a
      higher miR-10B expression than the NC group. However, the SD group demonstrated
      higher BDNF expression and lower miR-10B expression when compared with the CUPS
      group. Further investigation demonstrated that the BDNF is the direct target gene
      of miR-10B and BDNF expression, which is negatively correlated with the
      expression of miR-10B. In the sucrose consumption test, BNDF expression is
      positively correlated with the sucrose preference rate whereas miR-10B has an
      opposing correlation. Moreover, the open field test demonstrated that BNDF
      expression is positively correlated with the scores and the miR-10B expression is
      negatively correlated. These results indicate that sleep deprivation is closely
      linked with the downregulation of miR-10B and possibly the upregulation of BDNF
      in the hippocampus in the CUPS rats. 

PMID- 25755750
TI  - Long noncoding RNA linc-UBC1 is negative prognostic factor and exhibits tumor pro
      oncogenic activity in gastric cancer.
AB  - Despite the advances in the management of gastric cancer, the prognosis of
      advanced gastric cancer remains relatively poor. Thus, it is of urgent need to
      identify novel prognostic markers and therapeutic targets of gastric cancer. A
      growing volume of literature has indicated that lncRNAs are differentially
      expressed in a diverse array of cancer and play an important role in the
      development of cancer. Linc-UBC1, a recently identified long noncoding RNA, was
      initially found to be upregulated in bladder cancer. However, the role of linc
      UBC1 in gastric cancer remains to be elusive. In this study, we found that linc
      UBC1 was significantly upregulated in gastric cancer tissues compared to adjacent
      normal tissues. Furthermore, high linc-UBC1 expression was associated with lymph
      node metastasis, tumor size, TNM stage and poorer prognosis. Inhibition of linc
      UBC1 suppressed the proliferation, motility and invasion of gastric cancer cells.
      Our study suggests that linc-UBC1 may represent a novel diagnostic, prognostic
      biomarker and a potential therapeutic target of gastric cancer. 

PMID- 25755751
TI  - Expression of flotillin-2 in human non-small cell lung cancer and its correlation
      with tumor progression and patient survival.
AB  - INTRODUCTION: Recent studies have revealed that flotillin-2 (FLOT2) played
      important roles in cancer progression. The aim of this study was to investigate
      the clinicopathologic and prognostic significance of FLOT2 expression in human
      non-small cell lung cancer (NSCLC). METHODS: Quantitative real-time PCR (qRT-PCR)
      was performed to detect FLOT2 mRNA expression in lung cancer cell lines, normal
      bronchial epithelial cells, 24 pairs of NSCLC tissues and matched adjacent non
      tumor tissues. Immunohistochemistry (IHC) was performed to examine FLOT2 protein
      expression in paraffin-embedded tissues from 90 NSCLC patients. Statistical
      analyses were performed to evaluate the clinicopathological significance of FLOT2
      expression. RESULTS: FLOT2 mRNA expression was evidently up-regulated in lung
      cancer cell lines and NSCLC tissues compared with normal bronchial epithelial
      cells and adjacent non-tumor tissues. In the 90 cases of tested NSCLC samples,
      FLOT2 protein level was positively correlated with tumor stage, and lymph node
      metastasis. Patients with high FLOT2 expression had shorter overall survival
      compared with the low FLOT2 expression group. Univariate and multivariate
      analyses indicated that high FLOT2 expression was an independent poor prognostic
      factor for NSCLC patients. CONCLUSIONS: Our findings provided that high FLOT2
      expression was associated with poor outcomes in NSCLC patients, and FLOT2 could
      be a potential prognostic biomarker for lung cancer progression.

PMID- 25755752
TI  - Overexpression of Raf-1 and ERK1/2 in sacral chordoma and association with tumor
      recurrence.
AB  - Chordoma is a rare and low-malignant neoplasm which is considered to arise from
      notochord remnants. Due to its large resistance to chemotherapy and radiotherapy,
      surgical resection so far is the prior treatment for chordoma. However, the
      recurrence rate is high even after complete surgical resection. Recently,
      targeted cancer therapy has been demonstrated to be effective in several other
      tumors, while the related research on chordoma is rare. Mitogen-activated protein
      kinase signaling pathway is acknowledged to participate in tumor development, in
      which Raf-1 and extracellular regulated protein kinase 1/2 (ERK1/2) play vital
      roles. In this study, we evaluated the expression of Raf-1 and ERK1/2 by
      immunohistochemical staining in 42 chordoma tissue and 16 distant normal tissue.
      Moreover, we also investigated the correlations of Raf-1 and ERK1/2 expression
      with clinical features in sacral chordoma. Expression of Raf-1 and ERK1/2 was
      both significantly higher in sacral chordoma tissue than distant normal tissue (P
      = 0.008, P = 0.019). Raf-1 positive expression was related to surrounding muscle
      invasion (P = 0.032) and chordoma recurrence (P = 0.002), but the results did not
      indicate any association with patients' age, gender, tumor size and location.
      ERK1/2 was associated with tumor size (P = 0.044) instead of other clinical
      factors (P > 0.05). Spearman correlation test showed close relation between
      ERK1/2 and Raf-1 (P = 0.001, r = 0.518). Kaplan-Meier survival Curve and log-rank
      test showed that Raf-1 positive expression was associated with shorter continuous
      disease-free survival time (CDFS) (P = 0.001), while ERK1/2 had no relation to
      CDFS (P = 0.961). Conclusively, Raf-1 may be an important biomarker in predicting
      the prognosis of chordoma patients. 

PMID- 25755753
TI  - Anticancer effect of salidroside on colon cancer through inhibiting JAK2/STAT3
      signaling pathway.
AB  - Salidroside is considered to have anti-tumor properties. We investigate its
      effects on colon carcinoma SW1116 cells. Cell viability was assessed by CCK-8.
      Propidium iodide (PI) staining was used to determine the cell cycle by flow
      cytometry. The migration and invasion were detected by Transwell. Western blot
      was used to detect the expression of STAT3 signal related proteins. As the
      result, high concentrations of salidroside (10, 20. 50 MUg/ml) significantly
      inhibited proliferation of SW1116 cells in a parallelly, cell cycle arrest was
      increased at the G0/G1 phase after salidroside treatment. Furthermore,
      salidroside inhibited migration and invasion of SW1116 cells. Salidroside
      treatment decreased proteins expression of phosphorylation levels in JAK2/STAT3
      signaling, while MMP-2 and MMP-9 proteins levels were decreased and protein
      expression of VEGF and VEGFR-2 were down-regulated. In Conclusion, salidroside
      inhibited proliferation, decreased the migration and invasion of SW1116 cells in
      JAK2/STAT3-dependent pathway, the specific mechanisms need further study. 

PMID- 25755754
TI  - High expression of flotillin-2 is associated with poor clinical survival in
      cervical carcinoma.
AB  - AIMS: To investigate the expression and clinical significance of flotillin-2
      (FLOT2) in cervical cancer (CC). METHODS: We examined FLOT2 mRNA levels in 10
      pairs of cervical cancer and adjacent normal tissues. Immunohistochemistry was
      performed to analyze FLOT2 protein expression in 115 archived cervical cancer
      samples. The association between FLOT2 levels, clinicopathologic factors and
      prognosis was analyzed statistically as well. RESULTS: The cancer tissues of CC
      patients had clearly increased expression of FLOT2 at mRNA level as compared to
      adjacent nontumorous tissues. Survival analysis of CC patients indicated that
      FLOT2 expression was significantly associated with poor overall and local
      recurrence-free survival (P = 0.025 and P = 0.028, respectively). Moreover, FLOT2
      expression was significantly correlated with clinical stage, tumor
      differentiation, and lymph nodes metastasis. Multivariate analysis revealed that
      FLOT2 expression was an independent prognostic factor for overall survival in CC
      patients. CONCLUSION: FLOT2 may serve as an oncogene in the development of CC,
      and may serve as a clinicopathologic biomarker for prognosis in CC patients.

PMID- 25755755
TI  - Serum lemur tyrosine kinase-3: a novel biomarker for screening primary non-small
      cell lung cancer and predicting cancer progression.
AB  - PURPOSE: We aimed to determine the expression level of serum soluble lemur
      tyrosine kinase-3 (sLMTK3) in human non-small cell lung cancer (NSCLC), and to
      examine whether the s sLMTK3 level could be used as a biomarker to screen primary
      NSCLC and to predict lung cancer progression. METHODS: Serum levels of sLMTK3 in
      67 patients with primary NSCLC, 28 patients with lung benign lesion, and 53
      healthy volunteers were measured by sandwich ELISA. LMTK3 protein expression in
      NSCLC tissues and normal lung tissues was also detected by using
      immunohistochemical staining. Receiver operating characteristic (ROC) curve was
      selected to evaluate the sensitivity and the specificity of serum sLMTK3 level.
      RESULTS: The mean concentration of sLMTK3 in NSCLC group was significantly higher
      than in the lung benign lesion group (P < 0.001) and the healthy control group (P
      < 0.001). Higher sLMTK3 level was correlated with age (P = 0.013), tumor-node
      metastasis (TNM) stage (P < 0.001), and lymph node metastasis (P < 0.001) of
      NSCLC. In contrast to the normal lung tissues, increased LMTK3 expression was
      found in the NSCLC tissues, and was mainly located on the cytoplasm and the
      nuclei of cancer cells. For separating NSCLC from control group, the
      corresponding areas under the ROC curve (AUC) were 0.947 for sLMTK3 and 0.804 for
      CEA. With cutoffs of 10.05 ng/ml for sLMTK3 and 5.0 ng/ml for CEA respectively,
      the sensitivity and the specificity of sLMTK3 and CEA were, 80.60% and 97.53%,
      35.82% and 96.30%, respectively, indicating better diagnostic value of sLMTK3.
      CONCLUSIONS: The sLMTK3 level was significantly increased in human NSCLC, and
      could be used as a potential and valuable biomarker for screening primary NSCLC
      and for predicting the progression of patients with this malignancy.

PMID- 25755756
TI  - Detection of MGMT promoter methylation in glioblastoma using pyrosequencing.
AB  - Recent clinical trials on patients with glioblastoma revealed that O(6)
      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- 25755757
TI  - Effect of miR-18a overexpression on the radiosensitivity of non-small cell lung
      cancer.
AB  - The aim of the present study is to investigate whether there is a relationship
      between miR-18a expression and radiosensitization of non-small-cell lung caner
      (NSCLC). The relationship between miR-18a expression and clinicopathological
      characteristics was investigated. To determine whether the miR-18a expression
      levels were associated with radiotherapeutic efficacy, therapeutic response was
      evaluated by radiologic Response Evaluation Criteria in Solid Tumors (RECIST). To
      determine whether miR-18a was required for lung cancer cell radioresistance, A549
      cells were treated with different doses of ionizing radiation, following
      transfection with inhibitor miR-18a or inhibitor NC. We found that the level of
      miR-18a in NSCLC was strongly correlated with tumor differentiation (P = 0.026),
      regional lymph node metastasis (P = 0.013) and clinical TNM stage (P = 0.005).
      According to RECIST, miR-18a expression level was significantly associated with
      therapeutic response, exhibiting higher expression level in non-responsive
      patients. Furthermore, the depletion of miR-18a increased A549 cell
      radiosensitivity. In conclusion, we provide the evidence that down-regulation of
      miR-18a sensitizes NSCLC to radiation treatment, and it may help to develop a new
      approach to sensitizing radioresistant lung cancer cells by targeting miR-18a. 

PMID- 25755758
TI  - Effect of epigallocatechin gallate on uncoupling protein 2 in acute liver injury.
AB  - BACKGROUND: The aim of this study was to investigate the effect of
      epigallocatechin gallate (EGCG) on uncoupling protein 2 regulation in an acute
      liver injury-animal model. METHODS: Twenty seven male Wistar rats were divided
      into three groups: control group (n = 9), TAA group (n = 9): acute liver injury
      was induced by the intraperitoneal injection of thioacetamide (200 mg/kg) and
      EGCG/TAA (n = 9 rats): Epigallocatechin gallate was given two weeks prior to the
      induction of acute liver injury by thioacetamide. The levels of uncoupling
      protein 2, CRP, TNF-alpha and interleukins (IL) 6 and 18 were analyzed in the
      liver using PCR analysis. RESULTS: Q-PCR analysis showed that the genetic
      expression of UCP2, TNF-alpha and CRP in the EGCG/TAA group was the least in
      comparison to other groups (P <= 0.005). The IL-6 and IL-18 were upregulated
      after induction of acute liver injury, but this upregulation was significantly
      less in the group that received epigallocatechin gallate (EGCG/TAA) compared to
      the TAA group. In addition, histological examination showed a reduction in
      hepatocyte injury in EGCG/TAA compared to the TAA group. CONCLUSION:
      Epigallocatechin gallate administration prior to induction of acute liver injury
      down-regulates uncoupling protein 2 expression and reduces IL-6, IL-18, TNF-alpha
      and CRP.

PMID- 25755759
TI  - High serum miR-183 level is associated with the bioactivity of macrophage derived
      from tuberculosis patients.
AB  - As a major health threat, tuberculosis (TB) is resistant against the current
      therapeutic strategies. Increasing evidence indicates that miRNAs are implicated
      in various disorders by affecting specific target genes. Recently, the
      association of miRNAs with TB has also been established by several studies, and
      their potentials in the prognosis and treatment of TB have also been verified.
      miR-183 is shown to promote the activation of macrophage through NF-kappaB
      pathway. However, it is still unclear if serum miR-183 can be used to assess the
      activity of TB-associated macrophage. This study was aimed to address this issue.
      We employed qPCR assay to detect the expression level of miR-183 in blood from TB
      patients and healthy individuals. miR-183 abundance was found to be increased in
      serum samples from TB patients, compared with healthy controls. Further analysis
      revealed that miR-183 level is positively associated with the activity of
      macrophages from TB patients, evidenced by their increased phagocytosis rates and
      enzyme activity in high serum miR-183 group. In conclusions, high level of serum
      miR-183 is associated with the activity of macrophage originating from TB
      patients. 

PMID- 25755760
TI  - Diagnostic and prognostic potential of serum angiopoietin-2 expression in human
      breast cancer.
AB  - BACKGROUND: Accumulating evidence demonstrated a link of increased expression of
      Angiopoietin-2 (Ang-2) with invasive and metastatic phenotypes of various types
      of human cancers. However, until now, the serum level and its diagnostic and
      prognostic potential in breast cancer have not been investigated. METHODS: Enzyme
      linked immunosorbent assays were used to measure the levels of Ang-2.
      Sensitivity, specificity and area under curve (AUC) for serum Ang-2 levels were
      determined using receiver operator characteristic (ROC) analysis. Survival curves
      were plotted using the Kaplan-Meier method and differences in survival rates were
      analyzed using the log-rank test. Prognostic relevance of each variable to
      overall survival (OS) and disease-free survival (DFS) were analyzed using the Cox
      regression model. RESULTS: Serum expression of Ang-2 in patients with breast
      cancer was significantly higher than healthy control group (3171 +/- 1024 vs.
      1800 +/- 874 pg/ml, P < 0.0001). ROC curve analysis showed that at the optimal
      cut-off (2558.5 pg/ml), serum level of Ang-2 had a sensitivity of 78.3% and a
      specificity of 77.0% for distinguishing breast cancer patients from healthy
      controls with an area under the curve (AUC) of 0.836 (P < 0.001, 95% confidence
      interval: 0.787-0.885). The 5-year OS of high Ang-2 expression group was
      significantly shorter than that of low Ang-2 expression group (55.9% vs. 80.3%; P
      = 0.018). Moreover, the 5-year DFS of high Ang-2 expression group was also
      significantly shorter than that of low Ang-2 expression group (46.0% vs. 68.7%; P
      = 0.029). CONCLUSIONS: Our data indicate that serum Ang-2 level has potential
      value for early detection of breast cancer. Furthermore, Ang-2 has prognostic
      value in patients with breast cancer.

PMID- 25755761
TI  - Sex-specific association of the SPTY2D1 rs7934205 polymorphism and serum lipid
      levels.
AB  - The objective of the present study was to detect the association of the rs7934205
      single nucleotide polymorphism (SNP) near the Suppressor of Ty, domain containing
      1 gene (SPTY2D1) and serum lipid levels between males and females in the Mulao
      and Han populations. Genotyping of SPTY2D1 rs7934205 SNP was performed in 933 of
      Mulao and 865 of Han participants using polymerase chain reaction and restriction
      fragment length polymorphism. The T allele frequency was different between Mulao
      males and females (23.2% vs. 27.9%, P = 0.018). The genotype and allele
      frequencies were also different between Han males and females (P = 0.020 and P =
      0.004; respectively). Serum levels of apolipoprotein (Apo) A1 in Mulao males; and
      total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol
      (LDL-C), ApoA1 and ApoB in Mulao females were different between the CC and CT/TT
      genotypes (P < 0.05). Serum TC, ApoB levels in Han males, and ApoB levels in Han
      females were different between the CC and CT/TT genotypes (P < 0.05). The
      subjects with CT/TT genotype in both Mulao and Han males and females have more
      favorable lipid profiles than those with CC genotype. These findings suggest that
      the association between the SPTY2D1 rs7934205 SNP and serum lipid levels might
      have ethnic- and/or sex-specificity. 

PMID- 25755762
TI  - Correlation and prognostic significance of MMP-2 and TFPI-2 differential
      expression in pancreatic carcinoma.
AB  - Aberrant expression of matrix metalloproteinase (MMP)-2 and tissue factor pathway
      inhibitor (TFPI)-2 not only correlate with tumorigenesis, but also with tumor
      invasion and metastasis. This study aims to investigate the correlation and
      prognostic significance of MMP-2 and TFPI-2 differential expression in pancreatic
      carcinoma. Immunohistochemistry was used to evaluate MMP-2 and TFPI-2 expression
      in tumor tissues and corresponding non-tumor tissues from 122 patients with
      pancreatic carcinoma. The results showed that the expression of MMP-2 was
      significantly (P < 0.05) higher in tumor tissues (78.7%) than in adjacent non
      tumor tissues (27.9%), whereas the expression of TFPI-2 was significantly (P <
      0.001) lower in tumor tissues (27.9%) than in adjacent non-tumor tissues (79.5%).
      Spearman's rank correlation test showed a negative correlation between MMP-2 and
      TFPI-2 expression (r = -0.346, P < 0.001). Kaplan-Meier survival analysis showed
      that high MMP-2 expression was significantly correlated with decreased disease
      free survival (DFS) (P < 0.001) and overall survival (OS) (P < 0.001), while high
      TFPI-2 expression was significantly associated with increased DFS (P < 0.001) and
      OS (P < 0.001) of the patients. Multivariate analysis showed that high MMP-2
      expression can act as an independent predictive factor for poor DFS (P = 0.01);
      and low TFPI-2 expression as an independent prognostic factor for poor DFS (P <
      0.001) and OS (P < 0.001). In conclusion, our findings suggested that the
      differential expression of MMP-2 and TFPI-2 have a negative correlation in
      pancreatic carcinoma tissues; they may be considered as valuable biomarkers for
      prognosis of pancreatic carcinoma. 

PMID- 25755763
TI  - CD44v6 expression in patients with stage II or stage III sporadic colorectal
      cancer is superior to CD44 expression for predicting progression.
AB  - BACKGROUND: Currently, it is difficult to predict the prognosis of patients
      exhibiting stage II or stage III colorectal cancer (CRC) and to identify those
      patients most likely to benefit from aggressive treatment. The current study was
      performed to examine the clinicopathological significance of CD44 and CD44v6
      protein expression in these patients. STUDY DESIGN: We retrospectively
      investigated 187 consecutive patients who underwent surgery with curative intent
      for stage II to III CRC from 2007 to 2013 in the Beijing Civil Aviation Hospital.
      CD44 and CD44v6 protein expression levels were determined using
      immunohistochemistry and compared to the clinicopathological data. RESULTS: Using
      immunohistochemical detection, CD44 expression was observed in 108 (57.75%) of
      the CRC patients; and its detection was significantly associated with greater
      invasion depth, lymph node metastasis, angiolymphatic invasion, and a more
      advanced pathological tumor-lymph node-metastasis (TNM) stage. CD44v6 expression
      was observed in 135 (72.19%) of the CRC patients; and its expression was
      significantly associated with a poorly differentiated histology, greater invasion
      depth, lymph node metastasis, angiolymphatic invasion, and a more advanced
      pathological TNM stage. Expression of CD44v6 was higher than that of CD44 in
      stage II and stage III sporadic CRC. CONCLUSION: CD44v6 is a more useful marker
      for predicting a poor prognosis in stage II and stage III sporadic CRC as
      compared to CD44.

PMID- 25755764
TI  - TGFBI protein high expression predicts poor prognosis in colorectal cancer
      patients.
AB  - Transforming growth factor-beta-induced (TGFBI) serves as a linker protein and
      plays a role in the activation of morphogenesis, cell proliferation, adhesion,
      migration, differentiation and inflammation. High expression levels of the human
      TGFBI gene are correlated with numerous human malignancies. In order to explore
      the roles of TGFBI in the tumor progression of colorectal cancer, colorectal
      cancer specimens from 115 patients with strict follow-up were selected for the
      analysis of TGFBI by immunohistochemistry. The correlations between TGFBI
      expression and the clinicopathological features of colorectal cancers were
      evaluated. In the colorectal cancer tissues, TGFBI was mainly localized in the
      cytoplasm and stroma and scarcely in the nucleus. TGFBI expression in the
      cytoplasm and stroma was not found to be associated with age, gender, tumor
      histopathological grading, PT category and tumor location (P > 0.05 for each).
      However, high TGFBI expression in the cytoplasm and stroma correlated with lymph
      node metastasis, distant metastasis and Dukes stage (P < 0.05 for each). The
      survival rate was significantly lower in patients with high TGFBI expression than
      in those with low TGFBI expression. Furthermore, we found that tumor node
      metastasis (TNM) staging (HR: 2.963; 95% CI: 1.573-1.664; P = 0.000),
      differentiation (HR: 1.574; 95% CI: 1.001-2.476; P = 0.049) and high TGFBI
      cytoplasmic expression (HR: 3.332; 95% CI: 1.410-7.873; P = 0.000) proved to be
      independent prognostic factors for survival in colorectal cancer. In conclusion,
      TGFBI plays an important role in the progression of colorectal cancers and it is
      an independent poor prognostic factor for colorectal cancer patients. 

PMID- 25755765
TI  - Penicillar arterioles of red pulp in residual spleen after subtotal splenectomy
      due to splenomegaly in cirrhotic patients: a comparative study.
AB  - BACKGROUND: Following splenomegaly due to portal hypertension, pathologic
      characteristics include passive congestion and lymphoplasia. High venous pressure
      and hemodynamics can result in vascular proliferation and lymphoplasia, and
      promote splenic microcirculation and functional changes. The aim of this study
      was to determine the changes in penicillar arterioles (PAs) of red pulp in
      residual splenic tissue after subtotal splenectomy due to splenomegaly in
      cirrhotic patients to provide anatomic and physiologic evidence for reserved
      splenic surgery. METHODS: Thirteen patients with splenomegaly due to portal
      hypertension, who were treated surgically, comprised the splenomegaly group.
      After 8 years, we obtained another specimen by puncture biopsy from the residual
      spleen group. We designated patients with splenic trauma as the control group.
      The morphology of PAs under light microscopy was facilitated by EVG staining and
      immunohistochemistry for CD34. Semi-thin sections were HE-stained. The
      ultrastructure of PA endothelial cells was observed under electron microscopy.
      RESULTS: In the residual spleen group, diffuse distribution, tenuous elastic
      intima in the arterial wall, and continuity in PA of red pulp were seen under
      light microscopy. A significantly lower density and average cross-sectional area
      of PAs were observed in the residual spleen group compared with the splenomegaly
      and control groups (P < 0.01). A uniform mitochondrial matrix and a decreased
      number of ruptured cristae in PA endothelial cells were observed under electron
      microscopy. While there were some beneficial changes (splenic artery flow volume,
      portal venous diameter, and portal venous flow volume), the platelet and
      leucocyte counts were markedly increased in residual spleen. CONCLUSION: Subtotal
      splenectomy can eliminate the factors which precipitate splenomegaly (portal
      hypertension), improve the reconstruction of splenic capillaries, correct
      hypersplenism, and restore normal splenic function.

PMID- 25755766
TI  - Role of growth differentiation factor-5 and bone morphogenetic protein type II
      receptor in the development of lumbar intervertebral disc degeneration.
AB  - The present study was designed to evaluate the role of growth differentiation
      factor-5 (GDF-5) and bone morphogenetic protein type II receptor (BMPR-II) in the
      development of lumbar intervertebral disc degeneration (IDD). A total of 24
      patients with lumbar IDD (experiment group) and 6 patients with lumbar vertebral
      fracture (control group) were enrolled in the study. Tissue samples of IVD from
      the experiment group and control group were obtained during lumbar fusion
      operation, respectively. Fixation and decalcification of IVD tissue were
      performed, and then HE staining was carried out to observe the morphological
      changes of the lumbar IVD tissues. The expression of GDF-5 and BMPRII in human
      lumbar IVD was detected by immunohistochemical staining. HE staining results
      showed that non- and minimal degeneration was found in 11 cases (score range, 0
      3), moderate degeneration in 12 cases (score range, 4-8), and severe degeneration
      in 7 cases (score range, 9-12). According to the immunohistochemical results, the
      positive expression rates of GDF-5 and BMPRII in NP were higher than those in AF
      of the non- and minimal degeneration group, moderate degeneration group and
      severe degeneration group (all P < 0.05). However, no significant difference in
      GDF-5 or BMPRII positive expression was observed among the normal, non- and
      minimal, moderate and severe degeneration groups in neither NP area nor AF area
      (all P > 0.05). In conclusion, our results showed that GDF-5 and BMPRII expressed
      both in normal and degenerated IVD tissues, and GDF-5 might have an inhibition
      effect on degenerated lumbar IVD, suggesting that gene therapy may be a useful
      approach in producing physiological effects during early- and late-phase of
      lumbar IDD. 

PMID- 25755767
TI  - Downregulation of microRNA-504 is associated with poor prognosis in high-grade
      glioma.
AB  - Several previous reports indicated that microRNA-504 (miR-504) has an oncogenic
      function through negatively regulating p53. On the other hand, a recent study
      revealed that miR-504 inhibits cancer cell proliferation through targeting CDK6
      in hypopharyngeal squamous cell carcinoma (HSCC), suggesting the tumor
      suppressive role of this miRNA. However, the role of miR-504 in human malignant
      glioma remains unclear. Therefore, the aim of this study was to investigate the
      clinical significance of miR-504 expression in high pathological grade glioma.
      Quantitative real-time reverse transcriptive-PCR (qRT-PCR) was performed to
      examine miR-504 expression levels in 63 glioma tissues including 13 anaplastic
      astrocytomas (AA, WHO grade III) and 50 glioblastomas (GBM, WHO grade IV), as
      well as 10 non-neoplastic brain tissues. Associations between miR-504 expression
      and clinicopathological factors and prognosis of glioma patients were
      statistically analyzed. MiR-504 showed significant decreased expression levels
      both in AAs and GBMs relative to non-neoplastic brains (P <= 0.001,
      respectively). Additionally, low expression level of miR-504 was significantly
      associated with advanced WHO grade (P = 0.01). Moreover, Kaplan-Meier survival
      analysis showed that patients with low expression of miR-504 had significantly
      poor survival rate (P = 0.002). Cox regression analysis showed that miR-504
      expression was independent prognosis-predicting factor for malignant glioma
      patients (P = 0.038; risk ration = 2.5). Our results suggest that miR-504 may be
      a prognostic predictor and be involved in tumorigencity as a tumor suppressor of
      malignant glioma. 

PMID- 25755768
TI  - Progressive and painful wound as a feature of subcutaneous panniculitis-like T
      cell lymphoma (SPTCL): report of a case and review of literature.
AB  - Subcutaneous panniculitis-like T-cell lymphoma (SPTCL) is an uncommon extranodal
      non-Hodgkin lymphoma, with an aggressive course with no well-defined treatment.
      This article describes a 56-year-old man, treated surgically 7 months earlier for
      a subcutaneous nodosity near the left axilla, presenting with a progressive
      inflamed wound, pain, and high fever (39  degrees C). Treatment with systemic
      antibiotics and topical anti-inflammatory dressings failed. After 7 months, the
      patient was diagnosed with SPTCL based on biopsy results and a multidisciplinary
      consultation. While undergoing systemic chemotherapy with corticosteroid therapy,
      his wound become more painful, larger, and covered with necrotic tissue. Fifty
      days after chemotherapy with corticosteroid therapy, his wound became seriously
      painful and increasingly necrotic. He developed a serious stomachache and
      abdominal distension, rapidly became comatose, and died. The aim of this case
      report is to present our experience of the different clinical signs of SPTCL to
      expedite its early diagnosis in future. We summarize the main clinical
      characteristics of SPTCL as a rapidly progressing and increasingly painful wound
      with necrotic tissue, involving a multisystem disorder, which is easily
      misdiagnosed, responds poorly to corticosteroid and chemotherapy treatments, and
      has a high mortality rate. The pathological characteristics are early
      inflammation, advancing to profuse infiltration of the subcutaneous adipose
      tissues by CD3(+) and/or CD8(+) T-cell lymphoma cells. Clinicians must cooperate
      with pathologists and oncologists to diagnose this disease as soon as possible
      and to avoid a misdiagnosis. The use of antibiotic and painkillers should
      minimize the patient's discomfort and control rapid wound development. Future
      studies are required to investigate the optimal wound treatment and whether the
      necrotic tissue should be removed.

PMID- 25755769
TI  - Histological and immunohistochemical markers for progression prediction in
      transurethrally resected high-grade non-muscle invasive bladder cancer.
AB  - High-grade non-muscle-invasive bladder cancer (Non-MIBC) has a high risk of stage
      progression to muscle-invasive bladder cancer (MIBC) and could be managed either
      conservatively by transurethral resection of bladder tumor (TURBT) or more
      aggressively by radical cystectomy. The selection of patients who may benefit
      from early radical intervention is a challenge. To define useful prognostic
      markers for progression, we analyzed clinicopathological features and
      immunohistochemical expression patterns of E2F1, p27, survivin, p53, EZH2, IMP3,
      TSC1/hamartin, fatty acid synthase, androgen receptor, 14-3-3sigma, MAGEA4, and
      NY-ESO-1 on 118 cases of high-grade Non-MIBC. During the mean follow-up period of
      64.3 months, progression occurred in 18 patients (15.3%). Histologically, large
      amount of invasive component (> 50%) was noted in 35 cases (29.7%) and was
      strongly associated with progression. Among the 12 biomarkers, high expressions
      of E2F1 and nuclear p27 were noted in 46 cases (40.0%) and 14 cases (12.7%),
      respectively, and were associated with frequent progression. Using multivariate
      analysis, the proportion of invasive component and high E2F1 expression were
      independent prognostic factors for the prediction of progression. Our results
      indicated that large amount of invasive carcinoma component and high expressions
      of p27 and E2F1 were predictive markers for progression in Non-MIBC. Therefore,
      we suggest that these parameters, especially proportion of invasive carcinoma
      component and E2F1 expression, should be evaluated during pathologic examination
      and considered during selection of the appropriate management strategy for high
      grade Non-MIBC patients. 

PMID- 25755770
TI  - Elevated Aurora B expression contributes to chemoresistance and poor prognosis in
      breast cancer.
AB  - Aurora-B is a major kinase responsible for appropriate mitotic progression.
      Elevated expression of Aurora-B has been frequently associated with several types
      of cancer, including breast cancer. However, it is not clear whether the
      alteration contributes to tumor responses to therapies and prognosis. In this
      study, we conducted immunohistochemistry using antibodies against Aurora-B,
      S1981p-ATM, Ki67, and p53 in paraffin-embedded tumor tissues from 312 invasive
      breast cancer patients. The correlation between disease-free-survival (DFS) and
      Aurora-B expression was analyzed using the Kaplan-Meier method and log-rank test.
      A Cox proportional hazards regression analysis was used to determine whether
      Aurora-B was an independent prognostic factor for breast cancer. We found that
      Aurora-B expression was correlated with the proliferation index (P < 0.001) and
      p53 expression (P = 0.014) in breast cancer tissues. Further we found that Aurora
      B expression was associated with lymph node metastasis (P = 0.002) and
      histological grade (P = 0.001). Multivariate analyses indicated that elevated
      Aurora-B expression predicted a poor survival. In a subgroup of patients that
      received neoadjuvant chemotherapy, we found that elevated Aurora-B contributed to
      chemoresistance (P = 0.011). In conclusion, elevated Aurora-B expression in
      breast cancer patients contributes to chemoresistance and predicts poor
      prognosis. 

PMID- 25755771
TI  - Down-regulation of miR-497 is associated with poor prognosis in renal cancer.
AB  - INTRODUCTION: Clear cell renal cell carcinoma (ccRCC) is the most common type of
      cancer in the adult kidney, and the prognosis of metastatic ccRCC remains poor
      with high mortality. Recent study indicated that microRNAs (miRNAs) played
      critical roles in tumor progression. The aim of this study was to investigate the
      expression, biological role and clinical significance of miR-497 in ccRCC.
      METHODS: Quantitative real-time PCR (qRT-PCR) was performed to detect the
      expression of miR-497 in renal cancer cell lines and ccRCC tissues. The
      association between miR-497 expression and overall survival was estimated by the
      Kaplan-Meier method. Gain of function assays were performed in the 786-O renal
      cancer cell line. RESULTS: Expression of the miR-497 was significantly decreased
      in renal cancer cell lines and ccRCC tissues when compared with normal human
      proximal tubule epithelial cells and adjacent non-tumor tissues. Decreased miR
      497 expression was significantly associated with tumor stage, histological grade
      and lymph node metastases. Significantly shorter overall survival was observed in
      patients with lower expression of the miR-497. Overexpression of miR-497
      significantly inhibited renal cancer cell proliferation, migration and invasion.
      CONCLUSIONS: Our results demonstrated that miR-497 was decreased in ccRCC tissues
      and may provide a potential prognostic biomarker and a potential target for
      therapeutic intervention.

PMID- 25755772
TI  - Serum miR-125a-5p, miR-145 and miR-146a as diagnostic biomarkers in non-small
      cell lung cancer.
AB  - BACKGROUND: Lung cancer is becoming the leading cause of cancer-related deaths
      with high mortality worldwide and in China as well. Non-small-cell lung cancer
      (NSCLC) is the most common type of lung cancer accounting for approximately 85%
      of all cases. Over 70% of cases are at loco-regionally advanced stages or have
      distant metastasis at the time of presentation with subsequently poor prognosis.
      MiRNAs are stable molecules in blood and used as biomarkers for the early
      diagnosis of various malignancy. The purpose of this study was to evaluate
      whether circulating miR-125a-5p, miR-145 and miR-146a could be used as biomarkers
      for the diagnosis of NSCLC through measuring their expression and assess their
      relationship with clinical pathological factors. METHODS: Expression levels of
      serum miR-125a-5p, miR-145 and miR-146a were detected in 70 pairs of NSCLC
      patients and healthy controls using quantitative real-time PCR analysis. RESULTS:
      Serum miR-125a-5p, miR-145 and miR-146a were overexpressed in NSCLC patients
      compared with healthy controls. Their values of the area under the receiver 
      operating characteristic curve (AUC-ROC) were 0.71, 0.84 and 0.78. Optimal
      sensitivity and specificity were 73.53% and 55.71%, 92.75% and 61.43%, 84.06% and
      58.57%, respectively in differentiating NSCLC patients from healthy controls.
      CONCLUSIONS: These preliminary data suggest that serum miR-125a-5p, miR-145 and
      miR-146a may be useful noninvasive biomarkers for the clinical diagnosis of
      NSCLC.

PMID- 25755773
TI  - Clinicopathological features of angiomatoid fibrous histiocytoma: a series of 21
      cases with variant morphology.
AB  - We analyzed the clinicopathological features of angiomatoid fibrous histiocytoma
      (AFH) in 21 cases with emphasis on variant morphology. In our series, ten
      patients were male and eleven were female. The patients' mean age was 26.9 years
      old. Tumors were located on the lower limbs in eight cases, upper limbs in three,
      trunk in five, head and neck in four, and trachea in one. Microscopically,
      thirteen cases were characterized by typical AFH. Tumor cells showed marked tumor
      pleomorphism with giant hyperchromatic nuclei in two cases. Mitotic figures (2
      3/10HPF) were found in two cases. Focal necrosis was found in one case. A number
      of multinucleated giant cells were found in two cases. Two cases showed obvious
      myxoid change in the stromal. Prominent sclerosing changes in the stromal
      component were found in two cases. Immunohistochemistry staining showed tumor
      cells were positive for EMA, desmin, and CD68. Five cases demonstrated the
      presence of rearrangement of the EWSR1 gene by FISH detection. Only two patients
      had tumor recurrence at 3 and 6 months after tumor resection, respectively. In
      conclusion, AFH has variant histological patterns. The differential diagnosis
      includes inflammatory myofibroblastic tumor, aneurysmal fibrous histiocytoma,
      follicular dendritic cell tumor, and metastatic tumor of lymph node. 

PMID- 25755774
TI  - Long non-coding RNA CCAT2 is up-regulated in gastric cancer and associated with
      poor prognosis.
AB  - INTRODUCTION: Dysregulation of long non-coding RNAs (lncRNAs) play important
      roles in tumor progression. The aim of our study was to explore the
      clinicopathologic and prognostic significance of lncRNA CCAT2 expression in human
      gastric cancer. METHODS: Expression levels of lncRNA CCAT2 in 85 pairs of gastric
      cancer and adjacent non-tumor tissues were detected by quantitative real-time PCR
      (qRT-PCR). In order to determine its prognostic value, overall survival and
      progression-free survival were evaluated using the Kaplan-Meier method, and
      multivariate analysis was performed using the Cox proportional hazard analysis.
      RESULTS: Expression levels of lncRNA CCAT2 in gastric cancer tissues were
      significantly higher than those in adjacent non-tumor tissues. By statistical
      analyses, high lncRNA CCAT2 expression was observed to be closely correlated with
      higher incidence of lymph node metastasis and distance metastasis. Moreover,
      patients with high lncRNA CCAT2 expression had shorter overall survival and
      progression-free survival compared with the low lncRNA CCAT2 group. Multivariate
      analyses indicated that high lncRNA CCAT2 expression was an independent poor
      prognostic factor for gastric cancer patients. CONCLUSIONS: Our results suggested
      that up-regulation of lncRNA CCAT2 was correlated with gastric cancer
      progression, and lncRNA CCAT2 might be a potential molecular biomarker for
      predicting the prognosis of patients.

PMID- 25755775
TI  - In situ hybridization analysis of the expression of miR-106b in colonic cancer.
AB  - BACKGROUND: MicroRNA-106b (miR-106b) is thought to be an oncogenic microRNA that
      promotes tumor growth and metastasis. The potential predictive value of miR-106b
      was studied in colonic cancer patients. METHODS: The expression of miR-106b was
      examined in 180 colonic cancer cases using in situ hybridization (ISH) technique
      and was evaluated semi-quantitatively by examining the staining index. The
      Correlation of miR-106b expression and clinic-pathological features was analyzed
      by Spearman Rank Correlation. Wilcoxon signed rank test was used for assessing
      the expression difference of miRNA-106b between colonic cancerous and para
      cancerous ones, and their effects on patient survival were analyzed by a log-rank
      test and the Kaplan-Meier method. RESULTS: MiR-106b was higher expressed in para
      cancerous tissues, compared with colonic cancerous ones (P < 0.001). A positive
      correlation of miR-106b levels between colonic and para-cancerous tissues was
      also observed (CC = 0.523, P < 0.001). Furthermore, the expression of miR-106b
      was not significantly correlated with clinic-pathological parameters, including
      gender, age, histological grade, tumor size, pT stage, pN stage, pM stage and
      pTNM stage of the patients. Histological grade was positively correlated with pT
      stage (P = 0.011), pN stage (P = 0.036) and pTNM stage (P = 0.009). Patients
      expressing high levels of miR-106b both in colonic cancer tissues and para
      cancerous ones have a relatively longer survival time but the difference is not
      statistically significant (P = 0.16). CONCLUSIONS: The expression difference of
      miR-106b levels between colonic tissues and para-cancerous tissues is
      statistically significant, but the miR-106b levels were not quite correlated with
      clinic-pathological characteristics and overall survival times of patients with
      colonic cancer. Lower levels of miR-106b may be connected with neoplastic effects
      due to interference with TGF-beta signaling, providing evidence that down
      regulation of miR-106b might also play an important role in the progression of
      the disease. The study results are consistent with the literature and support the
      notion that miR-106b is an oncogenic microRNA.

PMID- 25755776
TI  - Association between BRAF V600E mutation and regional lymph node metastasis in
      papillary thyroid carcinoma.
AB  - BACKGROUND: BRAF V600E is the most frequent genetic alteration in papillary
      thyroid carcinoma (PTC); there are ongoing conflicts on its association with
      regional lymph node metastasis. And we aimed to test this association in a
      referred sample in a single institute in China. METHODS: We analyzed BRAF V600E
      mutational status in the primary lesion of 150 PTC cases in Peking Union Medical
      College Hospital (PUMCH) and their corresponding lymph node metastasis (if
      present and available) using a validated Amplification Refractory Mutation System
      Polymerase Chain Reaction (ARMS-PCR) method. RESULTS: Among 150 PTC cases, 121
      (80.6%) primary tumors harbored BRAF V600E mutation, 66.9% (81/121) and 79.3%
      (23/29) had regional lymph node metastasis (LNM) in cases detected with and
      without BRAF V600E mutation, respectively (P = 0.195). The BRAF V600E mutational
      status of most of the metastatic lesions was not different to that of their
      primary foci (73 out of 76 cases, 96.1%, Kappa value = 0.893). The 3 inconsistent
      cases were all mutation positive for primary tumors and mutation negative for
      LNM. CONCLUSION: No association was established between BRAF V600E mutation and
      regional lymph node metastasis in PTC in Chinese patients.

PMID- 25755777
TI  - MicroRNA-148b is down-regulated in non-small cell lung cancer and associated with
      poor survival.
AB  - BACKGROUND: The aim of this study was to clarify the clinicopathological
      significance of miRNA-148b (miR-148b) expression in NSCLC, and to explore the
      correlation between miR-148b level and the prognosis of patients with NSCLC.
      METHODS: 151 patients diagnosed with NSCLC between May 2007 and April 2012 were
      included in the present study. Real-time RT-PCR method was used to assess the
      expression levels of miR-148b. The differences between two groups were assessed
      using Student's t -test, and the Kaplan-Meier method was used to estimate overall
      survival. RESULTS: The expression of miR-148b was decreased in tumor tissues
      compared to corresponding adjacent normal lung tissues (0.37 +/- 0.12 vs. 1.00 +/
      0.53, P < 0.05). Low miR-148b expression was significantly associated with TNM
      stage (P = 0.014), lymph node metastasis (P = 0.031), and distant metastasis (P =
      0.008). Kaplan-Meier survival analysis showed that patients with low expression
      of miR-148b had significantly worse overall survival rates compared with those
      who had cancers with high miR-148b expression (log-rank test P = 0.039).
      Furthermore, multivariate Cox proportional hazards model analysis showed that miR
      148b expression was independently associated with overall survival of patients
      with NSCLC (HR = 2.357, 95% CI: 1.612-9.212, P = 0.011). CONCLUSION: our data
      indicate that decreased expression of miR-148b in NSCLC tissues has prognostic
      value.

PMID- 25755778
TI  - Low expression of long non-coding RNA LET inhibits carcinogenesis of cervical
      cancer.
AB  - INTRODUCTION: Long non-coding RNAs (lncRNAs) have been demonstrated to play key
      roles in tumorgenesis, and the lncRNA LET is down-regulated in several cancers.
      However, little is known about the function of lncRNA LET in human cervical
      cancer. The aim of this study was to investigate the clinical significance of
      lncRNA LET expression in cervical cancer. METHODS: We examined the expression of
      lncRNA LET in 94 cervical cancer tissues and matched adjacent non-tumor tissues
      using quantitative real-time PCR and analyzed its correlation with the
      clinicopathological features. RESULTS: The results showed that lncRNA LET
      expression in cervical cancer tissues was significantly down-regulated compared
      with the adjacent non-tumor tissues (P < 0.05). Decreased lncRNA LET expression
      was significantly correlated with FIGO stage, lymph node metastasis, and depth of
      cervical invasion (P < 0.05), but not other clinical characteristics. Moreover,
      cervical cancer patients with lncRNA LET lower expression have shown
      significantly poorer overall survival than those with higher lncRNA LET
      expression (P < 0.05). Univariate and multivariate analyses suggested that lncRNA
      LET expression served as an independent predictor for overall survival.
      CONCLUSIONS: Our data provided the first evidence that lncRNA LET may represent a
      prognostic marker and a potential therapeutic target for cervical cancer.

PMID- 25755779
TI  - Inhibitory effect of isothiocyanate derivant targeting AGPS by computer-aid drug
      design on proliferation of glioma and hepatic carcinoma cells.
AB  - Lipids metabolism was involved in the process of many types of tumor and
      alkylglycerone phosphate synthase (AGPS) was considered implicated in tumor
      process. Benzyl isothiocyanate (BITC) showed the inhibitory effect of tumor and
      AGPS activity, therefore, we screened a group of small molecular compound based
      on BITC by computer-aid design targeting AGPS and the results showed that the
      derivants could suppress the proliferation, the expression of tumor related genes
      such as survivin and Bcl-2, and the level of ether lipids such as
      lysophosphatidic acid ether (LPAe) and platelet activating factor ether (PAFe);
      however, the activity of caspase-3/8 was improved in glioma U87MG and hepatic
      carcinoma HepG2 cells in vitro. 

PMID- 25755780
TI  - Dysplastic changes in erythroid precursors as a manifestation of lead poisoning:
      report of a case and review of literature.
AB  - Dysplastic changes in erythroid precursors occur not only in patients with
      hematologic diseases, but also those with other diseases. Here, we report on a
      patient that presented with dysplastic changes in erythroid precursors due to
      lead poisoning from the intake of Chinese folk remedies. 

PMID- 25755781
TI  - Expression of miR-32 in human non-small cell lung cancer and its correlation with
      tumor progression and patient survival.
AB  - INTRODUCTION: miR-32 has recently been found to be implicated in many critical
      processes in various types of human cancer. However, its clinical significance in
      human non-small cell lung cancer (NSCLC) has not yet been elucidated. In the
      present study, we investigated the expression of miR-32 in NSCLC and analyzed its
      association with clinical features and prognosis of NSCLC patients. METHODS:
      Quantitative real-time PCR (qRT-PCR) was used to measure expression level of miR
      32 in lung cancer cell lines, normal bronchial epithelial cells, 90 pairs of
      tumor samples and adjacent non-tumor tissues. To determine its prognostic value,
      overall survival was evaluated using the Kaplan-Meier method. Univariate and
      multivariate analysis were performed using the Cox proportional hazard analysis.
      RESULTS: The expression of miR-32 was significantly decreased in lung cancer cell
      lines and NSCLC tissues compared with normal bronchial epithelial cells and
      adjacent non-tumor tissues (P < 0.05). This reduction of miR-32 was associated
      with tumor stage and lymph node metastasis (P < 0.05). Moreover, Kaplan-Meier
      analysis demonstrated that patients with low miR-32 expression had shorter
      overall survival time than those with high miR-32 expression (P < 0.05).
      Univariate analysis revealed statistically significant correlations between
      overall survival and miR-32 level, tumor stage and lymph node metastasis (P <
      0.05). Furthermore, miR-32 levels, tumor stage and lymph node metastasis were
      independently associated with overall survival (P < 0.05). CONCLUSIONS: Our
      results provided the first evidence that down-regulation of miR-32 was correlated
      with NSCLC progression, and miR-32 might be a potential molecular biomarker for
      predicting the prognosis of patients.

PMID- 25755782
TI  - IL-10-producing B cells involved in the pathogenesis of Coxsackie virus B3
      induced acute viral myocarditis.
AB  - BACKGROUND: Interleukin-10 (IL-10)-producing B cells, a subset of regulatory B
      cells, play critical roles in autoimmune and infectious diseases. However, the
      role of IL-10-producing B cells in acute viral myocarditis (AVMC) remains
      unknown. METHODS: BALB/c mice were intraperitoneally (i. p.) infected with
      coxsackievirus B3 (CVB3) to establish AVMC models (AVMC group), while control
      mice (control group) were treated with phosphate-buffered saline (PBS) i. p.
      According to the time after injection, the AVMC group mice or control group mice
      were randomly separated into 1 week and 2 week subgroup. Myocardial
      histopathological changes were observed by hematoxylin and eosin staining and the
      frequency of splenic IL-10-producing B cells was measured by flow cytometry.
      RESULTS: Histopathologic examination of heart tissues showed that mice infected
      with CVB3 developed AVMC. Compared with control group, the frequency of splenic
      IL-10-producing B cells was increased significantly in the AVMC group, with the 1
      week AVMC subgroup (3.58 +/- 0.47%) higher than the 2 week AVMC subgroup (2.50 +/
      0.42%) (all P < 0.05). CONCLUSIONS: IL-10-producing B cells are increased in
      CVB3-induced AVMC, indicating that IL-10-producing B cells may play an important
      role in the pathogenesis of CVB3-induced AVMC.

PMID- 25755783
TI  - The distribution of Mn2+ in rabbit eyes after topical administration for
      manganese-enhanced MRI.
AB  - PURPOSE: To analyze the distribution of Mn(2+) in rabbit eyes after topical
      administration of Mncl2 for manganese-enhanced MRI. METHODS: Forty-eight Chinese
      white rabbits were divided into three groups. In group 1 (n = 4), the baseline
      concentration of Mn(2+) in aqueous, vitreous and serum samples were analyzed. In
      group 2 and 3, the rabbits received one topical instillation (20 MUL) of Mncl2 (1
      mol * L(-1)). In group 2 (n = 40), aqueous, vitreous and serum samples were
      collected and analyzed at predetermined time points (0.5, 1, 2, 4, 6, 12, 24, 48,
      72 and 168 hours postdose). Assays were performed using inductively coupled
      plasma-mass spectrometer (ICP-MS). In group 3 (n = 4), after topical
      administration of Mncl2, dynamic manganese-enhanced MRI (MEMRI) was performed at
      predetermined time points. The signal-to-noise ratio (SNR) was calculated to
      evaluate the enhancements of eyes. RESULTS: After topical administration, the
      maximum concentrations of Mn(2+) in the aqueous and vitreous samples were 11.1641
      +/- 0.7202 (2 hours) and 1.5622 +/- 0.1567 (12 hours). In group 3, the maximum
      enhancement of aqueous humor (SNR = 108.81 +/- 10.65) appeared at 2 hours
      postdose, whereas, no significant changes were detected in vitreous. CONCLUSION:
      Mn(2+) could distribute into aqueous humor rapidly after topical administration
      of Mncl2, whereas, the concentration of Mn(2+) in vitreous body fluctuated in a
      narrow range over the course. The uptake of Mn(2+) in retina may involve several
      different pathways.

PMID- 25755784
TI  - Increased expression of microRNA-150 is associated with poor prognosis in non
      small cell lung cancer.
AB  - OBJECTIVES: The aim was to evaluate the clinical significance and prognostic
      value of tissue miR-150 expression in non-small cell lung cancer (NSCLC)
      patients. MATERIALS AND METHODS: Quantitative real-time PCR was used to analyze
      the expression of miR-150. Overall survival (OS) was estimated using the Kaplan
      Meier method, and the differences in survival were compared using the log-rank
      test. A Cox proportional hazards model was used for multivariate analysis.
      RESULTS: Mean miR-150 levels were significantly higher in NSCLC tissues compared
      with matched non-cancerous tissues (4.07 +/- 2.33 vs. 1.00 +/- 0.46, P < 0.0001).
      The level of miR-150 in NSCLC was strongly correlated with lymph node metastasis
      (P = 0.04), distant metastasis (P = 0.01) and clinical TNM stage (P = 0.02).
      Kaplan-Meier analysis showed that the cumulative 5-year OS rate was 40.8% in the
      high expression group, and 69.2% in the low expression group. The log-rank test
      showed that the OS rate of patients with high miR-150 expression was
      significantly poorer than that of the remaining cases (P = 0.007). CONCLUSION:
      Our data indicated that overexpression of miR-150 in NSCLC tissues has prognostic
      value.

PMID- 25755785
TI  - Evidence for epithelial-mesenchymal transition in cancer stem-like cells derived
      from carcinoma cell lines of the cervix uteri.
AB  - The cancer stem cell (CSC) paradigm is one possible way to understand the genesis
      of cancer, and cervical cancer in particular. We quantified and enriched ALDH1(+)
      cells within cervical cancer cell lines and subsequently characterized their
      phenotypical and functional properties like invasion capacity and epithelial
      mesenchymal transition (EMT). ALDH1 expression in spheroid-derived cells (SDC)
      and the parental monolayer-derived cell (MDC) line was compared by flow
      cytometry. Invasion capability was evaluated by Matrigel assay and expression of
      EMT-related genes Twist 1, Twist 2, Snail 1, Snail 2, Vimentin and E-cadherin by
      real-time PCR. ALDH1 expression was significantly higher in SDC. ALDH1(+) cells
      showed increased colony-formation. SDC expressed lower levels of E-cadherin and
      elevated levels of Twist 1, Twist 2, Snail 1, Snail 2 and Vimentin compared to
      MDC. Cervical cancer cell lines harbor potential CSC, characterized by ALDH1
      expression as well as properties like invasiveness, colony-forming ability, and
      EMT. CSC can be enriched by anchorage-independent culture techniques, which may
      be important for the investigation of their contribution to therapy resistance,
      tumor recurrence and metastasis. 

PMID- 25755786
TI  - Up-regulation of ROR2 is associated with unfavorable prognosis and tumor
      progression in cervical cancer.
AB  - AIMS: To investigate the clinical significance of receptor tyrosine kinase-like
      orphan receptor 2 (ROR2) in cervical cancer. METHODS: We examined ROR2 levels in
      8 pairs of surgically resected cervical cancer and adjacent normal cervical
      tissues by real-time PCR. Moreover, we performed immunohistochemistry to examine
      ROR2 expression in 94 paraffin-embedded cervical cancer samples and analyzed the
      association between ROR2 expression, clinicopathologic factors and prognosis.
      RESULTS: ROR2 expression was up-regulated in cervical cancer tissues compared
      with adjacent normal cervix. In paraffin-embedded cervical cancer samples, high
      expression of ROR2 was shown in 40 (42.6%) of 94 cases, also, it was
      significantly associated with tumor stage (P = 0.018) and lymph nodes metastasis
      (P = 0.013). Moreover, survival analysis showed that ROR2 expression was an
      independent prognostic factor of poor overall and recurrent free survival (P =
      0.045 and 0.001, respectively). CONCLUSION: These results indicate that ROR2 is
      significantly correlated with cancer progression and poor prognosis in cervical
      cancer.

PMID- 25755787
TI  - CA9 overexpression is an independent favorable prognostic marker in intrahepatic
      cholangiocarcinoma.
AB  - The aim of this study is to evaluate the expression of carbonic anhydrase IX
      (CA9) and to identify its prognostic significance in intrahepatic
      cholangiocarcinoma (IHCC). We performed immunohistochemistry (IHC) for CA9 in a
      total of 85 IHCCs. CA9 overexpression was observed in 38 of 85 (44.7%) IHCCs. CA9
      overexpression was related to tumors with intraductal growth than mass forming or
      periductal infiltrative type. CA9 overexpression was more observed in tumors with
      well/moderate differentiation than poor differentiation and without lymph node
      metastasis. No significant correlation was observed in CA9 overexpression with
      tumor size, pT, stage and lymphovascular invasion. Intrahepatic
      cholangiocarcinomas with CA9 overexpression showed better overall survival than
      that without expression (P = 0.001). In multivariate analysis, lymph node
      metastasis (95% CI: 2.103 (1.167-3.791), P = 0.013) was an independent poor
      prognostic factor. IHCC with CA9 overexpression showed a 0.5-fold (95% confidence
      interval, 0.328-0.944) lower risk of death compared with those of no or weak
      expression. CA9 overexpression was related to histologic differentiation and an
      independent good prognostic factor. 

PMID- 25755788
TI  - Typical or atypical progressive supranuclear palsy: a comparative
      clinicopathologic study of three Chinese cases.
AB  - Progressive supranuclear palsy (PSP) is an atypical parkinsonism, which is the
      third most common geriatric neurodegenerative disease. We reported three
      pathology-confirmed Chinese PSP cases with special focus on the pathological
      accumulations of tau, a-synuclein and A-beta in the three PSP brains. Cases 1 and
      2 initiated with extrapyramidal signs and gait disorders, while case 3 suffered
      behavioral abnormalities with cognitive decline at the beginning. In
      neuropathology, PSP-changes such as tau-positive tufed astrocytes,
      oligdendrocytes with the tau-positive coiled-body and threads and globose NFTs
      were widely seen in the basal ganglia, isocortex and allocortex, as well as in
      brainstem, cerebellum and spinal cord. In addition, numerous AGs were found in
      the hippocampus of cases 1 & 2, while Abeta amyloid depositions were found in
      hippocampus and leptomeningeal vessels of case 1 and in neocortex, entorhinal
      cortex, hippocampus, cingulate gyrus and amygdale of case 3. Vessel infarcts were
      observed in cases 1. Cortical laminar III necrosis in case 1 suggested the
      ischemic damage. Cervical spinal cords in cases 2 & 3 were obtained with tau
      positive globose NFTs, tufted astrocytes and neuropil threads were respectively
      found in the neurons of anterior horn and surrounding white matters. In summary,
      pathological examination is crucial for the ambiguous cases to exclude other
      neurodegenerative diseases. Furthermore, cervical spinal cord should be routinely
      examined in the PSP autopsy. 

PMID- 25755789
TI  - Diagnostic value of MCM2 immunocytochemical staining in cervical lesions and its
      relationship with HPV infection.
AB  - Cervical cancer remains the fourth most common cause of cancer-related deaths in
      women worldwide, and human papillomavirus infection represents the most important
      risk factor for the development of cervical cancer. Minichromosome maintenance
      protein-2 has been previously identified by DNA microarray and transcriptional
      profiling as genes that is overexpressed in cervical carcinomas. 183 cases were
      enrolled and tested with thin prep liquid-based cytology test. The expressions of
      human papillomavirus were detected and minichromosome maintenance protein-2
      immuncytochemical test was performed on liquid-based pap smears from the samples.
      Those results were compared with the cervical histopathology results. The
      positive expression rates of minichromosome maintenance protein-2 and high-risk
      type human papillomavirus increased with the severity of cervical lesions. The
      expression level of MCM2 was positively correlated with high-risk types of human
      papillomavirus. In cervical carcinoma and precancerous lesions, minichromosome
      maintenance protein-2 was overexpressed and positively correlated with the high
      risk types of human papillomavirus. As minichromosome maintenance protein-2
      immuncytochemical detection was better than genotyping of human papillomavirus,
      minichromosome maintenance protein-2 may serve as a useful marker in the
      screening of cervical carcinoma and precancerous lesions and improve the
      diagnosis of atypical squamous cell of undetermined significance. The joint
      application can improve the sensitivity and specificity of diagnosis. 

PMID- 25755790
TI  - The expression patterns of tight junction protein claudin-1, -3, and -4 in human
      gastric neoplasms and adjacent non-neoplastic tissues.
AB  - Recently, there is growing evidence that tight junction proteins are often
      abnormally regulated in human tumors. The function of tight junction proteins in
      the maintenance of normal epithelial physiology has been well discussed, but
      their role in the tumorigenesis of gastric cancer is less well defined. To
      explore the expression distinction of the tight junction proteins claudin-1, -3,
      and -4 expression in the gastric cancer, the expression of claudin-1, -3, and -4
      in 92 gastric cancer tissues and the non-neoplastic tissues adjacent to the
      tumors were examined by immunohistochemistry. Compared with adjacent non
      neoplastic tissues, the expression of claudin-1 was down regulated. However, the
      expression of claudin-3 and claudin-4 were up-regulated in gastric cancer tissue.
      In addition, the expression of claudin-3 is correlated with claudin-4 expression
      in gastric cancer. Our present study reveals that claudin-1, -3, and -4 protein
      expression altered between human gastric cancers and adjacent non-neoplastic
      tissues. 

PMID- 25755791
TI  - Combined detections of interleukin-33 and adenosine deaminase for diagnosis of
      tuberculous pleural effusion.
AB  - OBJECTIVE: To investigate the diagnostic accuracy of the combination of
      interleukin-33 (IL-33) and adenosine deaminase (ADA) for differentiating TPE from
      pleural effusions with the other etiologies. METHODS: Pleural effusion samples
      were collected from 32 TPE patients and 55 non-TPE patients. Pleural levels of IL
      33 and ADA were measured by ELISA. The corresponding biochemical indexes were
      also simultaneously determined. RESULTS: The pleural levels of IL-33 and ADA in
      the TPE group were significantly higher than those in the non-TPE group. With a
      cut-off value of 68.3 pg/ml, the sensitivity and specificity for IL-33 were 83.9%
      and 70.9%, respectively. While for ADA, the sensitivity and specificity were
      87.5% and 87.3%, respectively at a cut-off value of 10.25 U/L. Combined use of IL
      33 and ADA measurements further increased the sensitivity or specificity.
      CONCLUSION: Our study suggests that the applications of new biomarker IL-33,
      along with ADA, may serve as efficient diagnosis strategies in the management of
      pleural TB. Further studies at a large scale should be performed to validate our
      findings.

PMID- 25755792
TI  - Investigation on the DNA repaired gene polymorphisms and response to chemotherapy
      and overall survival of osteosarcoma.
AB  - The aim of the present study was to evaluate the influence of polymorphisms in
      NER and HRR pathways on the response to cisplatin-based treatment and clinical
      outcome in osteosarcoma patients. 214 osteosarcoma patients treated with
      cisplatin-based chemotherapy were collected between January 2008 and January
      2011. Genotypes of ERCC1 rs11615, ERCC2 rs1799793 and rs13181, NBN rs709816,
      RAD51 rs1801320, and XRCC3 rs861539 were conducted by Polymerase Chain Reaction
      Restriction Fragment Length Polymorphism (PCR-RFLP) assay. By conditional
      logistic regression analysis, patients carrying CC genotype of ERCC1 rs11615
      showed a significant more good responder than TT genotype, and the OR (95% CI)
      was 2.51 (1.02-6.85). In the Cox proportional hazards model, after adjusting for
      potential confounding factors, we found that individuals carrying CC genotype of
      ERCC1 rs11615 was associated with decreased risk of death from osteosarcoma, and
      the HR (95% CI) was 0.43 (0.15-0.93). In conclusion, our results suggest that
      ERCC1 rs11615 polymorphism in the DNA repair pathways play an important role in
      the response to chemotherapy and overall survival of osteosarcoma. 

PMID- 25755793
TI  - Significance of preoperative calculation of uterine weight as an indicator for
      preserving the uterus in pelvic reconstructive surgery.
AB  - Recently, increasing evidence has shown that uterus preservation is beneficial
      for pelvic organ prolapse (POP) patients, both physiologically and
      psychologically. However, the preoperative indicators for uterus preservation
      have rarely been examined. The current study was designed to determine the
      relationship between the preoperative evaluated uterus weight and the operation
      selection (preserving the uterus or not) in pelvic reconstructive surgery (PRS)
      using vaginal meshes. First, in a series of 96 patients undergoing hysterectomy,
      the uterine weight was calculated by preoperative ultrasound measurements, and
      was then compared with the postoperative actual weight of the uterus.
      Subsequently, in a series of 65 patients undergone PRS using vaginal meshes and
      preserving the uterus, the uterine weight was calculated by preoperative
      ultrasound measurements. Lastly, in a series of 43 patients with a uterine weight
      > 56.12 g who had undergone PRS using vaginal meshes, the operation success rate
      in patients with a preserved uterus was compared to patients for whom the uterus
      was not preserved. The results showed that uterus weight can be evaluated by
      ultrasound and used as a preoperative indicator for whether the uterus should be
      preserved or not in PRS when using vaginal meshes. It was indicated that
      preoperative evaluation of uterine weight is beneficial for surgical planning and
      guidance. 

PMID- 25755794
TI  - CREB1 gene polymorphisms combined with environmental risk factors increase
      susceptibility to major depressive disorder (MDD).
AB  - Major depressive disorder (MDD) is one of the most severe psychiatric disorders.
      The objective of this study was to explore the effects of CREB1 gene
      polymorphisms on risk of developing MDD and the joint effects of gene-environment
      interactions. Genotyping was performed by Taqman allelic discrimination assay
      among 586 patients and 586 healthy controls. A significant impact on rs6740584
      genotype distribution was found for childhood trauma (P = 0.015). We did not find
      an association of CREB1 polymorphisms with MDD susceptibility. However, we found
      a significantly increased risk associated with the interactions of CREB1
      polymorphisms and drinking (OR = 11.67, 95% CI = 2.52-54.18; OR = 11.52, 95% CI =
      2.55-51.95 for rs11904814; OR = 4.18, 95% CI = 1.87-9.38; OR = 5.02, 95% CI =
      2.27-11.14 for rs6740584; OR = 7.58, 95% CI = 2.05-27.98; OR = 7.59, 95% CI =
      2.12-27.14 for rs2553206; OR = 8.37, 95% CI = 3.02-23.23; OR = 7.84, 95% CI =
      2.93-20.98 for rs2551941). We also noted that CREB polymorphisms combined with
      family harmony and childhood trauma conferred increased susceptibility for MDD.
      In conclusion, polymorphisms in the CREB gene may not be independently associated
      with MDD risk, but they are likely to confer increased susceptibility by
      interacting with environmental risk factors in the Chinese population. 

PMID- 25755795
TI  - Evaluation of biomarker changes after administration of various neoadjuvant
      chemotherapies in breast cancer.
AB  - To assess the changes in estrogen receptor (ER), progesterone receptor (PR),
      human epidermal growth factor receptor 2 (HER2) and Ki-67 expression in breast
      cancer patients after various neoadjuvant chemotherapies. Data from 138 locally
      advanced breast cancer patients with histological diagnoses were reviewed.
      Seventy patients (group 1) were given 4 cycles of 500 mg/m(2) cyclophosphamide
      and 50 mg/m(2) pirarubicin every 21 days. Sixty-eight patients (group 2) were
      given 4 cycles of 500 mg/m(2) cyclophosphamide and 75 mg/m(2) docetaxel every 21
      days. The biomarker changes of the operated tumor tissues were compared with the
      initial core biopsies. ER, PR, HER2 and Ki-67 expression changed by 28.6%, 22.9%,
      17.1% and 54.3%, respectively, after neoadjuvant chemotherapy in group 1 and
      16.2%, 22.1%, 13.2% and 70.6%, respectively, after neoadjuvant chemotherapy in
      group 2. There were significant differences between the groups regarding ER and
      Ki-67 status changes, and these changes can be used to inform treatment
      strategies. 

PMID- 25755796
TI  - Association between VEGF polymorphisms (936c/t, -460t/c and -634g/c) with
      haplotypes and coronary heart disease susceptibility.
AB  - AIM: Our aim was to investigate the association between single nucleotide
      polymorphisms (SNPs) of vascular endothelial growth factor (VEGF) and coronary
      heart disease (CHD) susceptibility in Chinese Han population. METHODS: 144 CHD
      patients and 150 healthy individuals were enrolled in the study. Three SNPs
      (936C/T, -460T/C and -634G/C) of VEGF were chose and then were genotyped with
      Sequenom time-of-flight mass spectrometry (TOFMS). Odds ratio (OR) with 95%
      confidence interval (CI) were used to evaluate the association of genotypes and
      haplotypes and CHD susceptibility. RESULTS: The frequencies of -460T/C CC
      genotype (13.6%) was found higher in the case group than that of control group
      (6.7%), which indicated that CC genotype was a risk factor for CHD (OR=2.50, 95%
      CI=1.10-5.68). Correspondently, the C allele appeared to increase the risk of CHD
      (OR=1.54, 95% CI=1.07-2.22). For -634G/C polymorphism, the risk of the CC
      genotype carrier for CHD increased 2.24 fold compared to the wild genotype.
      Moreover, -634G/CC allele was significantly associated with CHD susceptibility
      (OR=1.65, 95% CI=1.15-2.36). In addition, +936C/T CT genotype and C allele
      appeared to be a genetic-susceptibility factors for CHD (OR=2.43, 95% CI=1.44
      4.10; OR=1.95, 95% CI=1.26-3.02). The haplotype analysis showed that T-C-T, C-C-C
      and C-G-C haplotypes all could increase the risk for CHD (OR: 2.43, 2.77 and
      2.33). CONCLUSION: we concluded VEGF polymorphisms were associated with CHD
      susceptibility. Moreover, the haplotypes of T-C-T, C-C-C and C-G-C all could
      increase the risk for CHD.

PMID- 25755797
TI  - Relationship between 11beta-HSD2 mRNA and insulin sensitivity in term small-for
      gestational age neonates after birth.
AB  - The aim of this study was to investigate the relationship between serum 11beta
      HSD2 mRNA level and insulin sensitivity in term small-for-gestational age (SGA)
      neonates after birth. The 38 infants were divided into two groups, the SGA group
      and the appropriate-for-gestational age (AGA) group. The placental 11beta-HSD2
      mRNA abundance and concentration of cortisol, fasting glucose, fasting insulin,
      adiponectin, visfatin and insulin-like growth factor-I (IGF-1) in the umbilical
      vein plasma were measured. The results showed that in the SGA group, neonates had
      lower levels of placental 11beta-HSD2 mRNA and serum cortisol, and higher fasting
      insulin and HOMA-IR compared to AGA group. For some insulin sensitivity relative
      factor, levels of serum adiponectin and IGF-1 were lower while visfatin was
      higher in the SGA group than AGA group. Correlation analyses revealed that 11beta
      HSD2 mRNA level had a negative correlation with fasting insulin, HOMA-IR and
      visfatin. 

PMID- 25755798
TI  - Association of PTPN22 polymorphsims and ankylosing spondylitis susceptibility.
AB  - BACKGROUND: As a susceptibility gene for AS, the polymorphsims of PTPN22
      associated with disease susceptibility. METHODS: We selected two SNPs of
      rs1217406 and rs1217414 within PTPN22 with Haploview software and investigated
      the relationship between the SNPs of PTPN22 gene and AS susceptibility. 120 AS
      patients and 100 healthy people were enrolled from Qilu Hospital of Shandong
      University. And we genotyped the SNPs of PTPN22 with PCR-RFLP method. RESULTS:
      The results showed that C allele (rs1217406) and T allele (rs1217414) both were
      risk factors for AS (OR: 3.12, 2.13). The persons with A-T, C-C or C-T haplotypes
      were more likely to suffer AS (OR: 3.17, 3.66, 4.011). CONCLUSIONS: Due to the
      close relationship of PTPN22 and AS, the study may be helpful for the early
      diagnosis and differential diagnosis.

PMID- 25755799
TI  - Abdominal pain, diarrhea, constipation--which symptom is more indispensable to
      have a colonoscopy?
AB  - BACKGROUND: Doctors perform colonoscopies when presented with various symptoms,
      including unexplained weight loss, rectal bleeding, changes in bowel habits,
      however many other symptoms such as abdominal pain, diarrhea and constipation may
      be more popular in outpatient department. As a result, we want to evaluate the
      three symptoms which is more need to have a colonoscopy. Abdominal pain, diarrhea
      and constipation are the main reasons for patients to visit the outpatient
      department of gastroenterology. And the colonoscopy is regularly recommended for
      outpatients with the above symptoms in China. The aim of this study was to
      evaluate the value of colonoscopy on the diagnosis of each single symptom of the
      three above and answer the question of my title-which symptom is more
      indispensable to have a colonoscopy? METHODS: Colonoscopic findings of 580
      outpatients with a single of these three common lower gastrointestinal symptoms
      were systematically analyzed in retrospect. RESULTS: In this study, no
      significant difference was found in the positive rate of colon polyps, cancer and
      ulcerative colitis among these three groups divided by symptoms. The incidence of
      colon polyps, cancer and colitis for the chronic abdominal pain, chronic diarrhea
      and constipation group are 20.8%, 57.1%, 42.9% respectively. The incidence of
      colon polyps and cancer increases with age. Among the age groups 13-39 years old,
      40-59 years and > 60 years, the incidence is 7.9%, 13.6%, 22.4% respectively.
      There is no significant difference in the incidence of colon polyps and colon
      cancer in our groups of symptoms. CONCLUSION: The results show the prevailing
      opinion that the indications of colonoscopy just refer to symptom and physical
      sign nowadays in China is inappropriate and it is best to take a full
      consideration of patient's age, auxiliary examinations, family diseases history
      and other factors.

PMID- 25755800
TI  - Association of ABCB1 polymorphisms and ulcerative colitis susceptibility.
AB  - OBJECTIVE: Multi-drug resistance gene 1 (ABCB1) is closely related to bowel
      diseases. Therefore, our study was aimed to evaluate the correlation between
      ABCB1 polymorphisms (C1236T and C3435T) and ulcerative colitis (UC)
      susceptibility. METHODS: A total of 61 UC patients and 64 healthy people
      participated in the study. Genotyping was conducted with the method of polymerase
      chain reaction-restriction fragment length polymorphism (PCR-RFLP). chi(2) test
      was used to evaluate the association of ABCB1 gene polymorphisms (C1236T and
      C3435T) and UC susceptibility. RESULTS: For ABCB1 C1236T polymorphism, the
      frequencies of CC genotype and C allele were found higher in the cases than those
      in the controls (CC: 36.1% vs. 20.3%; C: 58.2% vs. 41.4%), which indicated that
      the CC genotype and C allele might increase the risk for UC (OR = 3.39, 95% CI =
      1.28-8.97; OR = 1.97, 95% CI = 1.19-3.26). However, there were no statistical
      differences in the genotype or allele distribution of ABCB1 C3435T between the
      case and control group. CONCLUSION: The CC genotype and C allele of ABCB1 C1236T
      polymorphisms are significantly associated with UC susceptibility, so we conclude
      that ABCB1 C1236T polymorphisms might serve as genetic-susceptibility factors for
      UC. While, no remarkable relationship is observed between ABCB1 C3435T
      polymorphisms and UC.

PMID- 25755801
TI  - Aggressive fibromatosis of the leg and sacrococcygeal region: a report of two
      cases.
AB  - Aggressive fibromatosis is a rare soft tissue tumor that composes of
      myofibroblasts that arise from musculoaponeurotic structures. It usually affects
      the abdominal wall but may be also found in other less common sites including the
      head and neck, submucosa of the oral cavity, spinal, haunch and limbs,
      especially, the limbs and sacrococcygeal region are rare locations. We described
      two cases of aggressive fibromatosis. One was 3-year-old girl with aggressive
      fibromatosis arising from the right leg region. The other was 20-year-old female
      arising from in the sacrococcygeal region. They were resected with satisfied
      results. Pathological examination showed that they were composed of fibroblasts,
      fibrocytes and bundles of collagen fiber. The aggressive fibromatosis, although
      rare, should be differentiated from some other soft tissue tumors with similar
      histological features and different localizations of intra-abdominal, abdominal
      wall and extra-abdominal. 

PMID- 25755802
TI  - Scalp junctional nevus with malignant transformation (melanoma) metastatic to
      parotid lymph node region, cervical lymph nodes and the back: a case report and
      review of literature.
AB  - Parotid malignancy may occur as a primary neoplasm of the salivary tissue or as
      metastatic involvement of the parotid lymph nodes. Primary tumors of squamous
      cell carcinoma and malignant melanoma involving the skin of the head and neck
      have the potential to spread to lymph nodes of the parotid gland. Metastatic
      malignant melanoma to the back was exceptionally rare and no such reports have
      been noted in the literature. We reported an exceptional case of intraparotid
      lymph nodes metastasis of the right scalp junctional nevus with malignant
      transformation to malignant melanoma in a 48-year-old man. The patient presented
      with a mass in the parotid gland area, which was misdiagnosed as a primary
      parotid tumor and surgical removal was performed. Unfortunately, recurrence with
      newly developed metastatic lesions in the back and cervical lymph nodes occurred
      1 year after initial surgical management. This case is presented highlighting the
      unusual features of metastatic junctional nevus with malignant transformation to
      malignant melanoma of intraparotid lymph nodes, cervical lymph nodes and the
      back, which should help us to reduce misdiagnosis and obtain the best results. 

PMID- 25755803
TI  - Ewing's sarcoma family of tumors of the maxillary sinus: a case report of
      multidisciplinary examination enabling prompt diagnosis.
AB  - There have been approximately 10 reports in English literature of cases of
      Ewing's sarcoma family of tumors (EFT) arising in the maxillary sinus. In this
      location, some tumors mimic EFT, and are more frequently encountered. Herein, we
      present an additional case of an EFT originating in the maxillary sinus. The
      patient was a 15-year-old boy complaining of a non-tender swelling of the left
      cheek. Laboratory tests showed no abnormalities. Computed tomography and magnetic
      resonance imaging revealed a mass centered in the maxillary sinus with
      degeneration of the surrounding bones. Pathological examination along with flow
      cytometry and G-banding enabled the prompt diagnosis of EFT with the EWS/FLI1
      fusion gene. The patient is planned to undergo chemotherapy. An origin in the
      head and neck and the presence of the typical EWS/FLI1, in conjunction with an
      opportunity for immediate treatment, may predict a relatively better prognosis
      for EFT in our case. 

PMID- 25755804
TI  - Mixed endometrial stromal and smooth muscle tumor with heart metastasis: report
      of a case and review of literature.
AB  - We presented a case of mixed endometrial stromal sarcoma and smooth muscle cell
      tumor of the uterus with intravenous metastasis into the right heart. 50 hot
      mutated key genes of solid tumors were detected by next generation sequencing.
      The literature about the diagnostic and therapeutic strategies of the disease
      were reviewed. 

PMID- 25755806
TI  - Classic biphasic pulmonary blastoma with brain and axillary metastases: a case
      report with molecular analysis and review of literature.
AB  - Pulmonary blastoma is a rare series of malignant lung tumor, which contains three
      categories: classic biphasic pulmonary blastoma, pluropulmonary blastoma, and
      well-differentiated fetal adenocarcinoma. In this study, a 19-year old female
      suffering with classic biphasic pulmonary blastoma and metastases in brain and
      axilla was presented with special interest in clinicopathological presentations,
      immunohistochemical features, and molecular characterizations. However, this case
      was misdiagnosed initially with small biopsy specimen. Comprehensive management
      should be used for the treatment of this malignancy. 

PMID- 25755805
TI  - Beware of immunohistochemistry--report of a cytokeratin-, desmin- and INI-1
      negative pelvic desmoplastic small round cell tumor in a 51 year old woman.
AB  - We present a 51 year old female patient with a pelvic desmoplastic small round
      cell tumor with an unusual immunohistochemical profile, including absence of
      significant cytokeratin expression, complete negativity for desmin and widespread
      loss of nuclear INI-1 expression (>90% of tumor cells). The neoplastic cells were
      positive for epithelial membrane antigen (EMA), vimentin, and WT-1 (antibody
      against the C-terminus). The tumor showed classic histopathological features with
      no rhabdoid cells. Fluorescent in situ hybridization revealed EWSR1 gene
      rearrangement and absent SYT gene rearrangement. Reverse transcriptase polymerase
      chain reaction showed presence of EWSR1-WT1 transcript. 

PMID- 25755807
TI  - Cystic partially differentiated nephroblastoma in an adult: a case imitating the
      process of normal nephrogenesis along with corresponding WT1 expression.
AB  - Cystic partially differentiated nephroblastoma (CPDN) is extremely rare in
      adults. Only 2 cases have been documented in the English literature. Herein, we
      present a third case of CPDN with unique morphological and immunohistochemical
      features. A 45-year-old man had a multicystic right renal mass, with a maximum
      diameter of 3 cm on magnetic resonance imaging. Being unable to rule out
      malignancy, partial nephrectomy was performed. The surgically resected specimen
      contained a multicystic mass, 3 * 3 * 2.5 cm in size, without an expansile solid
      nodule. Histopathological examination revealed nephroblastomatous elements
      without identifiable blastema; transition from cap-mesenchyme-like cells to an
      immature glomerulus was observed and maturing tubules and a glomerulus were
      present. Despite the lack of a blastema, the diagnosis of CPDN was the most
      appropriate. Immunohistochemical WT1 expression imitated the pattern of ongoing
      normal nephrogenesis. Therefore, we believe that the blastema disappeared because
      of maturation. 

PMID- 25755808
TI  - Simultaneous double primary clear cell carcinomas of liver and kidney: a case
      report and review of literature.
AB  - Reported herein are simultaneous double primary clear cell carcinomas arising
      from liver and kidney. A 63-year-old man underwent a partial wedge nephrectomy of
      the right kidney in a surgical resection for hepatocellular carcinoma.
      Coincidently, on histology the tumors in liver and kidney were consisted of clear
      cancer cells, which arranged in haphazardly intermixed pattern without capsules.
      Immunohistochemically, the clear neoplastic cells in the liver were positive for
      HepPar-1, GPC3, and negative for nephrogenic markers; however, renal clear
      neoplastic cells were positive for CD10, RCC and Pax-8, but negative to liver
      derived markers. These findings led to the diagnosis of simultaneous double
      primary clear cell carcinomas of kidney and liver. Multiple primary carcinomas of
      kidney and liver, especially both are primary clear cell carcinomas, are
      extremely rare neoplasms, only 1 case has been reported previously until now. To
      our knowledge, this is a report of multiple primary carcinomas arising from the
      liver and kidney and reminders us of differentiation diagnosis with carcinoma
      metastasis. 

PMID- 25755809
TI  - Metachronous metastasis from the right colon adenocarcinoma to the vulva: an
      unusual report and literature review.
AB  - A 67-year-old woman who was presented to the gynecologist with a two-month
      history of heavy vaginal bleeding, after an excisional biopsy of vulvar mass, was
      diagnosed with the right colon adenocarcinoma metachronous metastasis to the
      vulva. Pathological examination preliminarily revealed by primary adenosquamous
      carcinoma of vulva. The original submitting pathologist and gynecologist were
      contacted to obtain the pathological and clinical information whenever possible,
      combining with a history of the right colon cancer, subsequently, which confirmed
      the diagnosis of vulvar metastatic adenocarcinoma. Distinguishing metastatic
      carcinoma from primary vulvar adenocarcinoma is crucial, since these carcinomas
      are different. Herein reports the second case of the right colon carcinoma
      presenting as a vulvar metastasis. This report also shows the differentiation,
      diagnosis and treatment of metastatic colon carcinoma and its metastatic route. 

PMID- 25755810
TI  - Clinicopathological characteristics of kidney mucinous tubular and spindle cell
      carcinoma.
AB  - Kidney mucinous tubular and spindle cell carcinoma (MTSpCC) is a rare renal low
      grade pleomorphic epithelial neoplasm featured by tubular and spindle cells with
      a relatively indolent behavior. This study was designed to clinicopathologically
      characterize two cases of kidney MTSpCC. Similar to other tumors, the data showed
      the diagnosis of MTSpCC relies on histological examination. Tumor cells stained
      strongly for CK19, CK20, and CK7 within the epithelioid component. Whereas
      evaluating MTSpCC clinically showed no specific symptoms, analyzing MTSpCC
      microscopically showed multiple elongated tubular branches of tumor cells that
      are closely arranged in cord-like manner under lightly stained myxoid stroma.
      MTSpCC also has the spindle cell area; the single tumor cell is small and nucleus
      round or oval. Immunohistochemical analysis of cytokeratins, electron microscopy,
      or genetic tests all improves the diagnosis. 

PMID- 25755811
TI  - Xanthogranulomatous gastritis associated with actinomycosis: report of a case
      presenting as a large submucosal mass.
AB  - Xanthogranulomatous gastritis (XGG) is a rarely encountered condition, and its
      causative mechanism is still unclear. Given that some types of
      xanthogranulomatous inflammation (XGI) are associated with pathogens, infection
      should be considered as a possible cause of XGG. Herein, we report a case of an
      86-year-old woman presenting with a large, bleeding lesion resembling a
      submucosal tumor. Distal gastrectomy was performed, and the surgically resected
      specimen revealed a mass measuring 6 * 4.5 * 3 cm and appearing yellowish on the
      cut surface. Histopathological examination revealed a few Actinomyces "sulfur
      granules" and cellular composition characteristic of XGI, supporting a diagnosis
      of XGG associated with actinomycosis. Gastric actinomycosis is a rare condition
      and has not previously been reported in association with XGG, although rare cases
      of XGI associated with actinomycosis have been documented in other organs. 

PMID- 25755812
TI  - A case of immunohistochemical false positive staining caused by incompatibility
      between a CD4 antibody and an autostainer.
AB  - Precise immunophenotyping of tumor cells by immunohistochemistry is complementary
      to morphological examination. It is critical for the correct histopathological
      diagnosis of lymphomas. In this paper, we report a case of T-cell lymphoma whose
      histopathological diagnosis was confounded by an immunohistochemical pitfall: a
      false positive caused by incompatibility between an antibody and an autostainer.
      In this case, based on CD4 immunohistochemistry of the affected lymph nodes, the
      T-cell lymphoma was diagnosed as CD4-positive at the onset, while it appeared
      discordantly to be CD4-negative at the second relapse. We noticed that CD4
      antibodies and autostainers of different suppliers (designated as suppliers X and
      Y) were used in an unqualified combination in immunohistochemistry at the onset:
      that is, the combination of an antibody supplied by X and an autostainer supplied
      by Y (designated as X-Y combination) was used at the onset. On the other hand,
      the Y-Y combination was at the second relapse. At the second relapse, flow
      cytometry of the affected lymph node showed infiltration of CD4-negative T-cell
      lymphoma. We reasoned that CD4 immunonegativity obtained by the Y-Y combination
      at the second relapse was specific, while CD4 immunopositivity by the X-Y
      combination at the onset was false positive. Immunohistochemical reexamination of
      the lymph node at the onset proved to be CD4-negative by not only the Y-Y but
      also X-X combinations, confirming our final diagnosis of nodal relapse of CD4
      negative T-cell lymphoma. This case illustrates the importance of using
      compatible combinations of antibodies and autostainers in diagnostic
      immunohistochemistry. 

PMID- 25755813
TI  - Decidualization of intranodal endometriosis in a postmenopausal woman.
AB  - Here we describe an unusual case of decidualized endometriosis detected in pelvic
      lymph nodes. The presence of intranodal ectopic decidua in pregnant women has
      been described. A few cases of decidualization of endometriotic foci in the
      pelvic or para-aortic lymph nodes have also been associated with pregnancy.
      However, decidualized intranodal endometriosis occurring in a postmenopausal
      woman has not been described. A 52-year-old woman presented with a very large
      adnexal mass. Menopause occurred at the age of 47, and she had been treated with
      hormone replacement therapy. She received a total abdominal hysterectomy with
      bilateral salpingo-oophorectomy and pelvic and para-aortic lymphadenectomy for
      clear cell carcinoma of the right ovary. Histological examination revealed the
      presence of ectopic decidua in several pelvic lymph nodes. The deciduas consisted
      of sheets of loosely cohesive, large, uniform, round cells with abundant
      eosinophilic cytoplasm. Typical of decidualization of intranodal endometriosis, a
      few irregularly shaped, inactive endometrial glands lined by single layers of
      columnar to cuboidal epithelium were present within the decidua. An
      immunohistochemical study revealed that the decidual cells were positive for
      CD10, vimentin, estrogen receptor and progesterone receptor, which indicated that
      progestin-induced decidualization had occurred in the intranodal endometriotic
      stroma. To the best of our knowledge, this case represents the first report of
      decidualized intranodal endometriosis occurring in association with hormone
      replacement therapy in a postmenopausal woman. Misdiagnosis of this condition as
      a metastatic tumor can be avoided by an awareness of these benign inclusions,
      supported by immunohistochemical staining results. 

PMID- 25755814
TI  - Intrahepatic splenosis mimicking liver cancer: report of a case and review of
      literature.
AB  - Intrahepatic splenosis is a rare situation occurred after traumatic splenic
      rupture or splenectomy. We report a 33 year old man with multiple isolated liver
      masses indistinguishable from primary and metastatic liver tumor by standard
      evaluation. The man underwent a splenectomy due to trauma at the age of three so
      that the hepatic splenosis was suspected. The final fine-needle biopsy
      pathological examination proved the diagnosis of intrahepatic splenosis. The
      importance of suspicion for this diagnosis should be highlighted when tumor-like
      lesions disclosed on imaging occurs in a patient with a splenic injury in the
      past. (99m)Tc labelled heat-denatured erythrocyte scintigraphy can be helpful to
      the diagnosis since it may avoid the performance of biopsies or surgical
      resections. 

PMID- 25755815
TI  - Spinal pleomorphic xanthoastrocytoma companied with periventricular tumor.
AB  - Pleomorphic xanthoastrocytoma (PXA) is a low grade tumor that occurs in
      supratentorial area of children and young adult. In the previous reports, PXA of
      spinal cord or multicentre was extremely rare. A 60-year-old patient of spinal
      PXA and periventricular tumor presented with waist pain and weakness of double
      legs for one month. Neuroimaging showed that a lesion at the level of L2-L3 and
      periventricular tumor. Postoperative microscopy indicated that WHO grade II PXA.
      Photomicrograph of the lesion showed spindle cells, marked nuclear and
      cytoplasmic pleomorphism, with foamy cytoplasm. Immunohistochemical staining
      showed that GFAP and S-100 were positive. This is a rare case of synchronous
      multicentric PXA. Physicians should be realized multicentric dissemination by
      meninges or cerebrospinal fluid in PXA patients. It is important to describe the
      particular case in order to better understanding of clinical features. 

PMID- 25755816
TI  - Synchronous of gastric adenocarcinoma and schwannoma: report of a case and review
      of literatures.
AB  - We presented a case of 80-year-old male with long term stomachache, marasmus and
      anaemia. Endoscopic evaluation suggested the malignant ulcerative tumor on the
      Gastric antrum, and biopsy confirmed the diagnosis of gastric adenocarcinoma.
      Surprisingly, in resected specimen the pathologist found a nodule just below the
      ulcer with clear boundary and gray-yellow section. Histologically, the whole
      lesion was composed with adenocarcinoma area and spindle tumor cells area. In the
      spindle tumor cells area, the cells with round or oval nuclei, eosinophilic
      cytoplasm, and these cells showed bundle or fence-like arrangement.
      Immunohistochemistry study presented positive expression of vimentin, S-100 and
      GFAP, negative expression of SMA, desmin, CD34, CD117 and Dog-1, which suggested
      the diagnosis of co-occurrence of gastric adenocarcinoma and schwannoma. To our
      knowledge, it is an extremely rare case that only two cases have been reported. 

PMID- 25755817
TI  - Primary juxtaovarian yolk sac tumor concurrent with an ipsilateral ovarian mature
      teratoma in an adult woman: a rare association.
AB  - OBJECTIVES: Yolk sac tumor (YST) is a rare neoplasm that primarily occurs in the
      ovary in children and young women. Previously, it has been reported that the
      teratomatous components can be recognized in part of YSTs or appear in the
      contralateral ovary. Here, we report a rare case of an adult woman with a
      juxtaovarian YST concurrent with an ipsilateral ovarian mature teratoma. METHODS:
      A 47-year-old woman found a pelvic mass for nine days and subsequently underwent
      debulking operation. The specimens were evaluated for detailed characterizations
      through gross examination, microscopy and immunohistochemistry. A literature
      review was performed and the pathogenesis was briefly discussed about the
      generation of an extraovarian YST concurrent with a teratoma. RESULTS: The right
      juxtaovarian tumor showed typical histological patterns of YST. Immunostaining
      demonstrated the YST nature of Gly-3 and AFP positive tumor cells. The
      ipsilateral ovarian tumor was a common mature cystic teratoma with chronic
      fibrotic changes. According to the differences of the origin and the
      differentiation of the two germ cell tumors, we suspect that the occurrence of
      the teratoma is earlier than the YST. CONCLUSIONS: To our knowledge, this is the
      first report of an adult woman with a juxtaovarian YST concurrent with an
      ipsilateral ovarian mature teratoma.

PMID- 25755818
TI  - Phenotypic variation of Val1589Met mutation in a four-generation Chinese pedigree
      with mild paramyotonia congenitia: case report.
AB  - Four generations of a Chinese family with a mild form of paramyotonia congenital
      was characterized in phenotype and genotype. For each member, clinical history,
      physical examination, laboratory tests, electrophysiological and gene analyses
      were recorded and carried out. A potassium loading, exercise and cold provocation
      were further tested to diagnose the clinical differentiation. All members shared
      the characteristics of mild muscle cramp and stiffness induced by exercise or
      exposed to cold. The symptoms were relieved after rest and warming. A Val1589Met
      mutation at exon 24 of the SCN4A gene appears in affected subjects, while healthy
      members had a point mutation at position 1513 at exon 24 of the SCN4A gene. The
      mild phenotype of the paramyotonia congenital in the family had a Val1589Met
      mutation in the SCN4A gene. Various phenotypes can exist among different
      families, indicating that family, individual, genetic or environmental factors
      influence symptoms. 

PMID- 25755819
TI  - Novel mutation of RUNX2 gene in a patient with cleidocranial dysplasia.
AB  - BACKGROUND: Cleidocranial dysplasia is a rare hereditary skeletal disorder due to
      heterozygous loss of function mutations in the RUNX2 gene that encodes runt
      related transcription factor 2 (RUNX2). Here we report a 52 year-old woman with
      cleidocranial dysplasia due to a novel RUNX2 mutation. CASE DESCRIPTION: A 52
      year-old Han Chinese woman presented with short stature and skeletal dysplasia
      that was first noted during early childhood. She was 153 cm in height and 40 kg
      in weight. Her skull was deformed with hypertelorism, midface hypoplasia,
      protrusion of chin, and dental abnormalities. Radiological examination revealed
      shortened clavicles and depressed skull bone and that were consistent with the
      clinical diagnosis of cleidocranial dysplasia. There was no family history of a
      similar skeletal disorder. We sequenced the RUNX2 gene and discovered a novel
      heterozygous mutation in exon 3 (c.476 del G, p.G159fs175X) that is predicted to
      cause a frameshift and premature termination that leads to the loss of the final
      347 amino acid residues. This severely truncated protein is expected to be
      inactive. LITERATURE REVIEW: RUNX2 gene controls osteoblast differentiation and
      chondrocyte maturation. Around 90 RUNX2 mutations have been discovered in
      patients with cleidocranial dysplasia. CLINICAL RELEVANCE: We identified a case
      of cleidocranial dysplasia due to a novel mutation of RUNX2 gene at exon 3 (c.476
      del G).

PMID- 25755820
TI  - Maxillary aggressive angiomyxoma showing ineffective to radiotherapy: a rare case
      report and review of literature.
AB  - Aggressive angiomyxoma, mostly originating in the female pelvis and peritoneum or
      in the male analogous sites, is a rare mesenchymal neoplasm characterized with
      infiltrative growth to adjacent tissue and local recurrence after primary
      excision. Herein, we report a case of aggressive angiomyxoma of maxilla in a 60
      year-old male patient for its rarity. The patient presented with a one-year
      history of progressively enlarging maxillary mass on left side. Before referred
      to our hospital, he was given a biopsy and diagnosed as aggressive angiomyxoma by
      immunohistochemical staining. After that, he underwent 60 Gy radiotherapy.
      Unfortunately, CT scan showed bigger mass infiltrated to adjacent facial soft
      tissues and bones compared with that of before radiotherapy. Besides that, he
      began to suffer with ingravescent headache. The mass was surgically removed and
      the diagnosis was confirmed by immunohistology in our hospital. As a case of
      aggressive angiomyxoma occurred in a rare site and experienced an ongoing growth
      in spite of radiotherapy, its characteristics was discussed with a brief
      literature review, which may aid further understanding of aggressive angiomyoma.

PMID- 25755821
TI  - Liposarcoma of the larynx: report of a case and review of literature.
AB  - Liposarcomas of the larynx are extremely rare tumors, with only 37 cases reported
      in the English or French literature to date. The first two cases of laryngeal
      liposarcomas were reported respectively by Kapur and Dockerty in 1968 [1, 2].
      Liposarcoma of the larynx is at high risk of local recurrence and seldom has
      metastatic potential. Prognosis for this tumor is better than that of non
      laryngeal liposarcoma. The present case is the first patient of primary
      liposarcoma of the larynx reported from China. A review of the literature was
      performed, and the presentation, position, pathological diagnosis, treatment and
      prognosis of the patients with liposarcoma of the larynx of the reported cases
      before are analyzed. 

PMID- 25755822
TI  - Myofibroblastic sarcoma in liver: a case report.
AB  - We recently encountered a giant Myofibroblastic sarcoma (MS) exceeding 23 cm in
      diameter which had developed in the liver in a 27-year-old female, and which was
      surgically resected with gratifying results. On surveillance imaging, a giant
      mass was detected in the right lobe of the liver. One the basis of morphology and
      immunohistochemistry features, the diagnosis of intermediate-grade
      myofibroblastic sarcoma (MS) was established. MS is extremely rarely found in the
      abdominal cavity. It is almost impossible to make a definite diagnosis before
      operation. However, the possibility of sarcoma should be taken into account for
      liver mass according to multimodal imaging features of the mass, especially when
      the diagnosis of common hepatic tumor was not supported by signs on imaging.
      Relative characteristic features on multimodal images maybe helpful to
      considerate the possibility of MS. This is the first reported case to date. 

PMID- 25755823
TI  - Clinicopathologic features of renal epithelioid angiomyolipoma: report of one
      case and review of literatures.
AB  - Epithelioid angiomyolipoma (EAML) is a rare renal mesenchymal tumor with
      malignant potential and is frequently associated with tuberous sclerosis complex
      (TSC). As metastasis of the tumor cells occur early, EAML is considered a
      potentially malignant tumor type and intrigues further research on it. Under the
      microscope, we could find the tumor was composed of atypical polygonal cells
      sheet mixed with classic angiomyolipoma (AML) components such as blood vessels
      with notable thick vascular walls, smooth muscle-like cells and adipocytes.
      Immunohistochemical studies showed that epithelioid cells were focally positive
      for vimentin, melanocytic markers (HMB-45), myoid markers (alpha-smooth muscle
      actin), CD34 and CD68; negative for cytokeratin, epithelial membrane antigen,
      CD10, and S-100. And the Ki67 index showed approximately 3%. Here, we report the
      morphological and immunohistochemical features of clinically or histologically
      malignant renal EAML and discuss its diagnosis, differential diagnosis and the
      prognosis. 

PMID- 25755824
TI  - Angel of human health: current research updates in toad medicine.
AB  - There are currently 34 genera and 410 species of toads in the world. The
      medicinal parts of toads mainly include their venom, skin, and clothing. The
      toad's venom and skin possess the same chemical components, mainly the toad venom
      lactone class, and their pharmacological effects primarily include the
      maintenance of strong heart, antitumor, antivirus, anti-infection, and analgesic
      effects. So far, the produces from the medicinal raw materials of the toad are
      widely used clinically around the world, especially in China, Japan, and South
      Korea. About 50 varieties of medicines are used in the clinical treatment of
      various complicated diseases in China, such as "Liushen pills" which was popular
      in the whole world. Toads are mainly used in treating malignant tumors (e.g.,
      liver cancer, gastric cancer, esophageal cancer, colon cancer, cervical cancer,
      among others), and some major diseases such as hepatitis B. Despite the
      therapeutic effects of toad-derived medicines on human health, there is
      insufficient research and development of toad-derived medicines by leading drug
      companies. In order to harness the beneficial effects of the resources of the
      toad species, it is the responsibility of global pharmaceutical researchers to
      develop and generate economically feasible toad-derived therapeutic products,
      while promoting maximum protection to the resources of the toad species. 

PMID- 25755825
TI  - E3 ubiquitin ligase Siah-1 downregulates synaptophysin expression under high
      glucose and hypoxia.
AB  - BACKGROUND: Diabetes is proved to be one of the independent risk factors for
      cognitive dysfunction. The pathophysiologic changes caused by diabetes including
      hyperglycemia and tissue hypoxia may contribute greatly to cognitive decline. In
      the present study, we demonstrate E3 Ubiquitin Ligase Siah-1 downregulates the
      key synaptic protein Synaptophysin expression under high glucose and hypoxia
      condition which may be the underlying factor leading to cognitive dysfunction in
      diabetic patients. METHODS: In this study, hypoxia (2% oxygen) and high glucose
      (50 mM) were used to treat primary neuronal culture. By using quantitative PCR
      and western blotting we determined the influence of hypoxia and high glucose on
      the expression of synaptophysin and Siah-1 and the phosphorylated forms of
      extracellular signal-regulated kinase (ERK). Knockdown of Siah-1, inhibitors for
      proteasome, lysosome and ERK kinase was employed to evaluate the role of Siah-1
      and ERK activity on the expression of synaptophysin. By immunoprecipitation we
      also examined the role of Siah-1 in the ubiquitination of synaptophysin under
      hypoxic and hyperglycemic condition. RESULTS: We demonstrated that hypoxia and
      high glucose together but not hypoxia or high glucose along mediated
      posttranscriptional reduction of synaptophysin with increased ERK phosphorylation
      and Siah-1 expression. The downregulation of synaptophysin was reversed by
      inhibition of ERK and Siah-1 knockdown. Overexpression of Siah-1 accelerated the
      degradation of synaptophysin under hypoxia and high glucose conditions and
      promoted the ubiquitination of synaptophysin. CONCLUSIONS: The present results
      demonstrate that Siah-1 is the key factor that contributes to hypoxia and high
      glucose mediated synaptophysin degradation.

PMID- 25755826
TI  - Development of a new model for the induction of chronic kidney disease via
      intraperitoneal adenine administration, and the effect of treatment with gum
      acacia thereon.
AB  - Oral adenine (0.75% w/w in feed), is an established model for human chronic
      kidney disease (CKD). Gum acacia (GA) has been shown to be a nephroprotective
      agent in this model. Here we aimed at developing a new adenine-induced CKD model
      in rats via a systemic route (intraperitoneal, i.p.) and to test it with GA to
      obviate the possibility of a physical interaction between GA and adenine in the
      gut. Adenine was injected i.p. (50 or 100 mg/Kg for four weeks), and GA was given
      concomitantly in drinking water at a concentration of 15%, w/v. Several plasma
      and urinary biomarkers of oxidative stress were measured and the renal damage was
      assessed histopathologically. Adenine, at the two given i.p. doses, significantly
      reduced body weight, and increased relative kidney weight, water intake and urine
      output. It dose-dependently increased plasma and urinary inflammatory and
      oxidative stress biomarkers, and caused morphological and histological damage
      resembling that which has been reported with oral adenine. Concomitant treatment
      with GA significantly mitigated almost all the above measured indices.
      Administration of adenine i.p. induced CKD signs very similar to those induced by
      oral adenine. Therefore, this new model is quicker, more practical and accurate
      than the original (oral) model. GA ameliorates the CKD effects caused by adenine
      given i.p. suggesting that the antioxidant and anti-inflammatory properties
      possessed by oral GA are the main mechanism for its salutary action in adenine
      induced CKD, an action that is independent of its possible interaction with
      adenine in the gut. 

PMID- 25755827
TI  - Potential roles of Centipede Scolopendra extracts as a strategy against EGFR
      dependent cancers.
AB  - Centipede Scolopendra, a commonly used traditional Chinese medicine, has been
      shown to have anti-cancer effects. In this study, the inhibitory effect of
      alcohol extracts of Centipede Scolopendra (AECS) was more prominent when treating
      cells highly expressing epidermal growth factor receptor (EGFR) (A431 and
      HEK293/EGFR cells versus HEK293 cells). The elution profiles of AECS on cell
      membrane chromatography (CMC) column showed that AECS could bind to EGFR, and
      competition studies indicated that AECS and gefitinib may have direct competition
      at a single common binding site on EGFR. SiRNA knockdown of EGFR in A431 cells
      attenuated AECS effects, suggesting that EGFR was a target mediated by AECS. In a
      cell culture system, AECS dramatically induced apoptosis of A431 and HEK293/EGFR
      cells, which was associated with the effects on Bcl-2 family. Furthermore, AECS
      could alter EGFR kinase activity and reduce phosphorylation of EGFR and
      downstream signaling players AKT and Erk1/2. The mechanism of AECS to inhibit
      high-EGFR expression cell proliferation is due to its ability to induce apoptosis
      and modulate the EGFR pathway. This study might provide a novel therapy for
      cancer with high-EGFR expression. 

PMID- 25755828
TI  - Specificity of motor axon regeneration: a comparison of recovery following
      biodegradable conduit small gap tubulization and epineurial neurorrhaphy.
AB  - Functional recovery is often unsatisfactory after lesions in the peripheral
      nervous system despite the strong potential for regeneration and advances in
      microsurgical techniques. Axonal regeneration in mixed nerve into inappropriate
      pathways is a major contributing factor to this failure. In this study, the rat
      femoral nerve model of transection and surgical repair was used to evaluate the
      specificity of motor axon regeneration as well as functional and morphological
      recovery using biodegradable conduit small gap tubulization compared to
      epineurial neurorrhaphy. 12 weeks after nerve repair, the specificity was
      assessed using the retrograde neurotracers TB and DiI to backlabel motor neurons
      that regenerate axons into muscle and cutaneous pathways. To evaluate the
      functional recovery of the quadriceps muscle, the quadriceps muscle forces were
      examined. The quadriceps muscle and myelinated axons were assessed using
      electrophysiology and histology. The results showed that the specificity of motor
      axon regeneration (preferential reinnervation) was significantly higher when the
      nerve transection was treated by biodegradable conduit small gap tubulization and
      there was no significant difference between the two suture methods with respect
      to the functional and morphological recovery. This study demonstrated that the
      quicker and easier biodegradable conduit small gap tubulization may get more
      accurate reinnervation than traditional epineurial neurorrhaphy and produced
      functional and morphological recovery equal to traditional epineurial
      neurorrhaphy. 

PMID- 25755829
TI  - Melatonin attenuates inflammation of acute pulpitis subjected to dental pulp
      injury.
AB  - Acute pulpitis (AP), one of the most common diseases in the endodontics, usually
      causes severe pain to the patients, which makes the search for therapeutic target
      of AP essential in clinic. Toll-like receptor 4 (TLR4) signaling is widely
      involved in the mechanism of pulp inflammation, while melatonin has been reported
      to have an inhibition for a various kinds of inflammation. We hereby studied
      whether melatonin can regulate the expression of TLR4/NF-KB signaling in the pulp
      tissue of AP and in human dental pulp cells (HDPCs). Two left dental pulps of the
      adult rat were drilled open to establish the AP model, and the serum levels of
      melatonin and pro-inflammatory cytokines, including interleukin 1beta (IL-1beta),
      interleukin 18 (IL-18) and tumor necrosis factor alpha (TNF-alpha), were assessed
      at 1, 3 and 5 d post injury. At the same time points, the expression of TLR4
      signaling in the pulp was explored by quantitative real-time PCR and
      immunohistochemistry. The AP rats were administered an abdominal injection of
      melatonin to assess whether melatonin rescued AP and TLR4/NF-KB signaling. Dental
      pulp injury led to an approximately five-day period acute pulp inflammation and
      necrosis in the pulp and a significant up-regulation of IL-1beta, IL-18 and TNF
      alpha in the serum. ELISA results showed that the level of melatonin in the serum
      decreased due to AP, while an abdominal injection of melatonin suppressed the
      increase in serum cytokines and the percentage of necrosis at the 5 d of the
      injured pulp. Consistent with the inflammation in AP rats, TLR4, NF-KB, TNF-alpha
      and IL-1beta in the pulp were increased post AP compared with the baseline
      expression. And melatonin showed an inhibition on TLR4/NF-KB signaling as well as
      IL-1beta and TNF-alpha production in the pulp of AP rats. Furthermore, melatonin
      could also regulate the expression of TLR4/NF-KB signaling in LPS-stimulated
      HDPCs. These data suggested that dental pulp injury induced AP and reduced the
      serum level of melatonin and that supplementation with melatonin may have a
      protective effect on AP by modulating TLR4/NF-KB signaling in the pulp and in
      pulp cells. 

PMID- 25755831
TI  - Impact of mitochondrial telomerase over-expression on drug resistance of
      hepatocellular carcinoma.
AB  - BACKGROUND: The efficacy of chemotherapy in patients with hepatocellular
      carcinomas still poor due to multidrug resistance. This study aimed to
      investigate the impact of the over-expressed mitochondrial human telomerase
      reverse transcriptase on multidrug resistance of hepatocellular carcinomas.
      METHODS: HepG2 and SK-Hep1 cell lines were used. And sensitivity to
      chemotherapeutic drugs was detected. RESULTS: Mitochondrial human telomerase
      reverse transcriptase over-expression in hepatocellular carcinomas cells could
      significantly reduce its sensitivity to multiple chemotherapeutic drugs in vitro
      and in vivo. Hepatocellular carcinomas cells over-expressing mitochondrial human
      telomerase reverse transcriptase showed a significantly higher mitochondrial
      membrane potential, a markedly lower activated caspase-3 after drug treatment,
      and an increased mtDNA copy number, which explained the drastically decreased
      drug-induced apoptosis of hepatocellular carcinomas cells with mitochondrial
      human telomerase reverse transcriptase over-expression. CONCLUSION: Over
      expressed mitochondrial human telomerase reverse transcriptase may increase the
      mtDNA copy number and inhibit the activation of mitochondrial apoptotic pathway
      to contribute to the multidrug resistance of hepatocellular carcinomas cells.

PMID- 25755830
TI  - Visualization of in vivo thromboprophylactic and thrombolytic efficacy of
      enoxaparin in laser-induced vascular endothelial injury model using multiphoton
      microscopy.
AB  - Enoxaparin is used postoperatively for the prevention of venous thromboembolism.
      In vitro studies and clinical trials have demonstrated the anticoagulant and
      antithrombotic efficacy of enoxaparin. In this study, we visualised
      thromboprophylactic and thrombolytic efficacy of enoxaparin in a laser-induced
      thrombus formation model in vivo using two-photon laser-scanning microscopy
      (TPLSM). Thrombus was induced by the selective irradiation of vascular
      endothelium in arterioles of the cecum of green fluorescent protein transgenic
      mice. The thromboprophylactic and thrombolytic efficacy of enoxaparin was
      visualised in vivo real-time using TPLSM. Platelet adhesion, aggregation, and
      platelet-dependent thrombus formation were observed in the laser-induced thrombus
      formation model with reproducibility. Laser-induced thrombus formation was
      significantly inhibited by enoxaparin pretreatment as the thromboprophylactic
      agent, as compared with control. The mean thrombus volumes were 652 microcubic
      meters in mice pretreated with enoxaparin and 8906 microcubic meter in control
      mice. Enoxaparin reduced the volume of laser-induced thrombus when using it as a
      thrombolytic agent. The mean rate of reduction was 59 percent. In a
      lipopolysaccharide-induced sepsis model, thromboprophylactic efficacy of
      enoxaparin was also observed in vivo in real-time. In vivo thromboprophylactic
      and thrombolytic efficacy of enoxaparin can be visualised at the single platelet
      level in the laser-induced endothelium injury model using TPLSM. 

PMID- 25755832
TI  - Cathepsin S silencing induces apoptosis of human hepatocellular carcinoma cells.
AB  - This study was to investigate the potential molecular mechanisms underlying the
      Cathepsin S (CTSS) silencing induced apoptosis of Hepatocellular Carcinoma (HCC)
      cells with lentivirus-mediated RNA interference. Real-time quantitative PCR and
      western blot assay were performed to detect the mRNA and protein expression of
      CTSS, respectively, in 13 HCC cell lines with different metastatic potentials.
      Results showed MHCC97-H cells had the highest CTSS expression. Therefore, MHCC97
      H cells were used in following experiments. Then, lentivirus-mediated RNAi was
      employed to silence CTSS expression (shCTSS). Annexin V/FITC staining showed NF
      kappaB was activated in shCTSS cells treated with conditioned medium from shCTSS
      PAR2 cells. This implies a probable positive correlation between PAR2 and CTSS.
      In addition, results demonstrated CTSS induced apoptosis of HCC cells and
      increased their chemosensitivity via regulating NF-kappaB and activating cleaved
      caspase-3. Our results indicate that CTSS silencing by lentivirus mediated RNAi
      can significantly induce apoptosis and chemosensitivity of MHCC97-H cells. This
      provides an attractive anti-cancer strategy and a novel strategy for the
      treatment of human HCC. 

PMID- 25755833
TI  - Low miR-34a and miR-192 are associated with unfavorable prognosis in patients
      suffering from osteosarcoma.
AB  - BACKGROUND: p53 is a well-known tumor suppressor gene involved in malignancy.
      Many microRNAs (miRNAs) have recently been identified as key components of p53
      signaling networks, owing to the central role of p53 in many processes, these p53
      regulated miRNAs may possess important role in osteosarcoma. METHODS: The
      expression of six p53-related miRNAs (miR-34 family [including miR-34a, 34b and
      34c], miR-31, miR-192, and miR-215) in 80 pairs of osteosarcoma and corresponding
      noncancerous bone tissues were estimated by real-time quantitative reverse
      transcription polymerase chain reaction (RT-qPCR), and the associations of miRNAs
      expression with clinicopathological factors, p53 status, and survival of patients
      were analyzed. RESULTS: We found that among all six miRNAs, miR-34 family, -192,
      and -215 had decreased levels, whereas the level of miR-31 was increased (p<0.05)
      in tumor compared with corresponding noncancerous bone tissues, and miR-192/215
      in patients with p53 positive expression was lower than those with negative p53.
      Kaplan-Meier analysis demonstrated that osteosarcoma patients with low miR-34a
      (P=0.000) and miR-192 (P=0.022) expression had poorer disease-free survival
      (DFS). Moreover, disease-free survival (DFS) was shorter for patients with low
      miR-34a and miR-192 expression (P=0.007) and the combination of low miR-192 with
      p53 positive expression (P=0.000). Furthermore, the multivariate analysis
      identified that low miR-34a expression, the combination of low miR-34a and miR
      192 expression levels and the combination of low miR-192 with p53 positive were
      independent biomarkers of shorter DFS. CONCLUSIONS: Together, these results
      suggest that p53-associated miR-34a and miR-192 expression could be novel
      prognosis biomarkers for surgically treated osteosarcoma.

PMID- 25755834
TI  - The overexpression membrane type 1 matrix metalloproteinase is associated with
      the progression and prognosis in breast cancer.
AB  - Membrane type 1 matrix metalloproteinase (MT1-MMP) has been demonstrated to play
      an important role in tumor progression. The aim of the present study was to
      analyze the expression of MT1-MMP in breast cancer and its correlation with
      clinicopathologic characteristics, including the survival of breast cancer
      patients. In our results, MT-MMP1 was up-expressed in breast cancer tissues
      compared with ductal hyperplasia tissues in microarray data (GSE2429). MT1-MMP
      mRNA and protein expression was markedly higher in breast cancer tissues than in
      normal breast tissues (P=0.005 and P=0.037, respectively). Using
      immunohistochemistry, high levels of MT1-MMP protein were positively correlated
      with the status of clinical stage (I-II vs. III-IV; P=0.043), lymph node
      metastasis (absence vs. presence; P=0.024), and distant metastasis (No vs. Yes;
      P=0.017) of breast cancer patients. Patients with higher MT1-MMP expression had a
      significantly shorter overall survival time than did patients with low MT1-MMP
      expression. Multivariate analysis indicated that the level of MT1-MMP expression
      was an independent prognostic indicator (P<0.001) for the survival of patients
      with breast cancer. In conclusions, MT1-MMP plays an important role on breast
      cancer aggressiveness and prognosis and may act as a promising target for
      prognostic prediction. 

PMID- 25755835
TI  - Activation of the calcium-sensing receptor before renal ischemia/reperfusion
      exacerbates kidney injury.
AB  - Activation of the calcium-sensing receptor (CaSR) by ischemia/reperfusion (I/R)
      favours apoptosis in cardiomyocytes, hepatocytes and neurons. Its role in renal
      I/R is unknown. We investigated the impact of pharmacological preactivation of
      the CaSR on kidney structure and function in a murine model of bilateral renal 30
      min ischemia and 48-hour reperfusion, and in a 6-year cohort of kidney transplant
      recipients (KTR). C57BL/6J mice were administered daily with CaSR agonist, R-568,
      or with vehicle for 48 hours. Evaluation of serum urea and creatinine levels,
      renal histology and urine metabolome by nuclear magnetic resonance showed that R
      568 was not nephrotoxic per se. Following I/R, serum urea and creatinine levels
      increased higher in R-568-treated animals than in controls. Jablonski's score was
      significantly greater in R-568-treated kidneys, which showed a higher rate of
      cell proliferation and apoptosis in comparison to controls. Next, we
      retrospectively identified 36 patients (10.7% of our cohort) who were treated by
      CaSR agonist, cinacalcet, at the time of kidney transplantation (KTx). After
      matching these to 61 KTR upon type of donor, cold ischemic time, residual
      diuresis, and donor age, we observed that delayed graft function, i.e. need for
      dialysis in the first week after KTx, occurred in 42 and 23% of cinacalcet
      treated and control groups, respectively (p<=0.05). These data suggest that
      pharmacological preactivation of the CaSR before renal I/R exacerbates kidney
      injury. 

PMID- 25755836
TI  - Gene methylation profiles as prognostic markers in ovarian clear cell and
      endometrioid adenocarcinomas.
AB  - Ovarian cancer is a cancer of high mortality. Aberrant gene methylation of tumor
      suppressor genes has been shown to be related to the development of malignancy.
      This study aimed to investigate the methylation of various genes in ovarian clear
      cell adenocarcinoma (OCCA) and ovarian endometrioid adenocarcinoma (OEA) and
      evaluate methylation biomarkers in terms of patient chemo-response and outcome.
      Eight candidate genes from 66 OCCA and 51 OEA patients were evaluated by
      methylation-specific polymerase chain reaction and capillary electrophoresis.
      Clinico-pathological parameters and patient outcomes were analyzed. The
      frequencies of gene methylation in RASSF1A (79% vs. 59%, p=0.025), E-cadherin
      (30% vs. 10%, p=0.011), and DLEC1 (71% vs. 43%, p=0.003) were higher in the
      patients with OCCA than in those with OEA. The chemo-resistant group had a
      significantly higher percentage of E-cadherin methylation (36.7% vs. 16.1%,
      p=0.036) than the chemo-sensitive group. In multivariate analysis (log-rank
      test), advanced stage (4.79 [2.10-10.94], p<0.001) was the only risk factor for
      mortality. Those with methylation of more than two out of three genes (E
      cadherin, DLEC1, and SFRP5) had a shorter disease-free survival (1.89 [1.07
      3.32], p=0.028) and overall survival (3.29 [1.57-6.87], p=0.002) than those with
      methylation of one or no gene. In advanced-stage malignancies, those with more
      than two out of the three gene methylations also had a shorter overall survival
      (3.86 [1.63-9.09], p=0.002) than those with methylation of only one or no gene.
      Patients with OCCA have different patterns of gene methylation than those with
      OEA. Methylation of the E-cadherin, DLEC1 and SFRP5 genes can be a prognostic
      biomarker for OCCA and OEA. 

PMID- 25755837
TI  - Arg16Gly and Gln27Glu beta2 adrenergic polymorphisms influence cardiac autonomic
      modulation and baroreflex sensitivity in healthy young Brazilians.
AB  - The association between functional beta2 adrenergic receptor (beta2-AR)
      polymorphisms and cardiac autonomic modulation is still unclear. Thus, two common
      polymorphisms in the beta2-AR gene (Gln27Glu beta2 and Arg16Gly beta2) were
      studied to determine whether they might affect tonic and reflex cardiac
      sympathetic activity in healthy young subjects. A total of 213 healthy young
      white subjects of both genders (53% female), aged 18-30 years (23.5+/-3.4 y), had
      their continuous blood pressure curves noninvasively recorded by Finometer at
      baseline, and other hemodynamic parameters, as cardiac autonomic modulation,
      baroreflex sensitivity, and allele, genotype, and diplotype frequencies
      calculated. Associations were made between Arg16Gly beta2 and Gln27Glu beta2
      polymorphisms and between beta2-AR diplotypes and all variables. The heart rate
      was significantly lower (P<0.001) in the presence of homozygous Arg/Arg alleles
      (60.9+/-1.5 bpm) than in that of Arg/Gly heterozygotes (65.9+/-1.0 bpm) or
      Gly/Gly homozygotes (66.3+/-1.2 bpm). Homozygous carriers of Arg16 allele had an
      alpha index (19.2+/-1.3) significantly higher (P<0.001) than that of the subjects
      with the Gly allele Gly/Gly (14.5+/-0.7) or Arg/Gly (14.6+/-0.7). Furthermore,
      the recessive Glu27Glu and the heterozygous Gln27Glu genotypes had a higher
      percentage of low-frequency components (LF%) than the homozygous Gln27Gln (15.1%
      vs. 16.0% vs. 8.2%, P=0.03, respectively). In healthy young subjects, the
      presence of beta2-AR Arg16 allele in a recessive model was associated with higher
      baroreflex sensitivity, and increased parasympathetic modulation in studied
      individuals. 

PMID- 25755838
TI  - Notch signaling induces epithelial-mesenchymal transition to promote invasion and
      metastasis in adenoid cystic carcinoma.
AB  - Epithelial-mesenchymal transition (EMT) is considered to have pivotal roles in
      the invasive and metastatic of Adenoid cystic carcinoma (AdCC) which is marked by
      local infiltration and distant metastasis. Notch signaling abnormity has been
      implicated as important molecular events in recent next generation sequencing
      studies of AdCC, but the detail is still unclear. This study was designed to
      investigate the expression of Notch signaling pathway and its relation with EMT
      program in AdCC. We constructed custom-made Tissue microarray (TMA) to evaluate
      the immunoreactivity of Notch signaling and EMT program and found that Notch
      signaling increase consecutively from NSG, PMA to AdCC, suggesting Notch
      signaling pathway may be associated with human AdCC progression. Then, we carried
      out Pearson correlation analysis and showed a close correlation of Notch
      signaling and EMT progression. When blocking Notch signaling pathway with gamma
      secretase inhibitor DAPT, EMT progression was decreased and migration and
      invasion ability were declined. Collectively, these findings suggest the vital
      roles of Notch signaling pathway in AdCC progression through their relationship
      with EMT progress. Targeting Notch signaling may provide further understanding of
      the mechanism of invasion and metastasis of AdCC as well as potential clinical
      therapeutics. 

PMID- 25755839
TI  - Irregularities in glucose metabolism induced by stress and high-calorie diet can
      be attenuated by glycyrrhizic acid.
AB  - Stress and high-calorie diet increase the risk of developing metabolic syndrome.
      Glycyrrhizic acid (GA) has been shown to improve hyperglycaemia and dyslipidaemia
      under various physiological conditions. This study was aimed at examining the
      effects of stress and GA on glucose metabolism under short- or long-term stress.
      Forty-eight Sprague Dawley rats were divided into two groups with constant stress
      induced by light (300-400 lux) for either 14 days (short-term stress) or 28 days
      (long-term stress). Within each group, the rats were subdivided into three
      treatment groups i.e. Group A (control group): high-calorie diet (HCD) only;
      Group B: HCD + stress (14 or 28 days) and Group C: HCD + stress (14 or 28 days) +
      GA (100 mg/kg). The blood glucose concentrations of the rats exposed to 14-day
      stress were elevated significantly and GA lowered blood glucose concentration
      significantly in the 14-day exposure group. The 28-day exposure group adapted to
      stress as shown by the lower adrenaline level and gluconeogenic enzymes
      activities in most of the tissues than the 14-day exposure group. With regards to
      adrenaline and corticosterone, GA was found to increased adrenaline significantly
      in the short-term exposure group while lowering corticosterone in the long-term
      exposure group. GA-treated short- and long-term exposure groups had significant
      reduction in hexose-6-phosphate dehydrogenase activities in the visceral adipose
      tissues and quadriceps femoris respectively. The results may indicate the role of
      GA in improving blood glucose concentration in individuals exposed to short-term
      stress who are already on a high-calorie diet via selective action on
      gluconeogenic enzymes in different tissues. 

PMID- 25755840
TI  - De-repression of myelin-regulating gene expression after status epilepticus in
      mice lacking the C/EBP homologous protein CHOP.
AB  - The C/EBP homologous protein CHOP is normally present at low levels in cells but
      increases rapidly after insults such as DNA damage or endoplasmatic reticulum
      stress where it contributes to cellular homeostasis and apoptosis. By forming
      heterodimers with other transcription factors, CHOP can either act as a dominant
      negative regulator of gene expression or to induce the expression of target
      genes. Recent work demonstrated that seizure-induced hippocampal damage is
      significantly worse in mice lacking CHOP and these animals go on to develop an
      aggravated epileptic phenotype. To identify novel CHOP-controlled target genes
      which potentially influence the epileptic phenotype, we performed a
      bioinformatics analysis of tissue microarrays from chop-deficient mice after
      prolonged seizures. GO analysis revealed genes associated with biological
      membranes were prominent among those in the chop-deficient array dataset and we
      identified myelin-associated genes to be particularly de-repressed. These data
      suggest CHOP might act as an inhibitor of myelin-associated processes in the
      brain and could be targeted to influence axonal regeneration or reorganisation. 

PMID- 25755841
TI  - Neurogenic function in rats with unilateral hippocampal sclerosis that
      experienced early-life status epilepticus.
AB  - Status epilepticus in the adult brain invariably causes an increase in
      hippocampal neurogenesis and the appearance of ectopic cells and this has been
      implicated as a causal factor in epileptogenesis. The effect of status
      epilepticus on neurogenesis in the developing brain is less well characterized
      and models of early-life seizures typically do not reproduce the hippocampal
      damage common to human mesial temporal sclerosis. We recently reported that
      evoking status epilepticus by intra-amygdala microinjection of kainic acid in
      post-natal (P) day 10 rats caused substantial acute neuronal death within the
      ipsilateral hippocampus and rats later developed unilateral hippocampal sclerosis
      and spontaneous recurrent seizures. Here, we examined the expression of a
      selection of genes associated with neurogenesis and assessed neurogenic function
      in this model. Protein levels of several markers of neurogenesis including
      polysialic acid neural cell adhesion molecule, neuroD and doublecortin were
      reduced in the hippocampus three days after status epilepticus in P10 rats. In
      contrast, protein levels of neurogenesis markers were similar to control in rats
      at P55. Pulse-chase experiments using thymidine analogues suggested there was a
      reduction in new neurons at 72 h after status epilepticus in P10 rats, whereas
      numbers of new neurons labelled in epileptic rats at P55 with hippocampal
      sclerosis were similar to controls. The present study suggests that status
      epilepticus in the immature brain suppresses neurogenesis but the neurogenic
      potential is retained in animals that later develop hippocampal sclerosis. 

PMID- 25755842
TI  - Myocardial oxidative metabolism, blood flow and efficiency in rapid pacing
      induced heart failure in dogs.
AB  - PURPOSE: Heart failure is the final common pathway for most forms of heart
      disease, and is characterized by a reduced energy status. Myocardial oxygen
      consumption (MV02) is closely related to the main determinants of systolic
      function (heart rate, pressure and contractility). The aim of the study was to
      compare myocardial blood flow, metabolism and mechanical efficiency in rapid
      pacing induced heart failure in dogs. METHODS: 5 dogs were paced for 3 weeks at
      240 bpm, with regular follow up of hemodynamic characteristics. Coronary blood
      flow and oxidative metabolism were evaluated with [(15)O] water and
      [(11)C]acetate clearance respectively, in baseline conditions (B) and after 3
      weeks of rapid pacing (3 wk RP) using positron emission tomography. RESULTS:
      Three weeks of rapid pacing in a dog model resulted in a severely depressed left
      ventricular function (LV dP/dtmax 3698 +/- 314 mmHg (B) vs. 1365 +/- 103 mmHg (3
      wk RP)). On the contrary myocardial blood flow 1.29 +/- 0.11 ml/min/g (B) vs.
      1.05 +/- 0.07 ml/min/g (3 wk RP) and oxidative metabolism 0.178 +/- 0.1 min(-1)
      (B) vs. 0.161 +/- 0.1 min(-1) (3 wk RP) remained essentially unchanged,
      indicating a reduced efficiency and a change in O2 utilization. CONCLUSIONS:
      Heart failure induced by rapid ventricular pacing in dogs provokes a clearly
      reduced mechanical efficiency, illustrating the occurrence of a metabolic
      remodeling in heart failure induced by rapid pacing.

PMID- 25755843
TI  - Waist related anthropometric measures - simple and useful predictors of coronary
      artery disease in women.
AB  - AIM: To compare the waist related anthropometric measures like waist
      circumference, waist-to-height ratio (WHtR), waist - hip ratio (WHR) and body
      mass index (BMI) as predictors of coronary artery disease (CAD) in women.
      METHODS: The study included 88 women aged 40-80 years. Waist circumference, hip
      circumference, height, weight, age, and other covariates were collected by
      questionnaire. The primary endpoint was incident coronary heart disease that was
      reported by physician. The data was analyzed statistically using chi(2)-test for
      quantitative data and student t-test. The significance of the results as
      determined in 95.0% confidence interval. RESULTS: The mean age was 59.07 +/-
      11.53 in the study group and 54.36 +/- 10.84 in the control group. The waist
      circumference in the study group was higher (95.443 +/- 11.187) than the control
      group (74.886 +/- 6.672) (p < 0.001). The mean waist to hip ratio (WHR) was 0.96
      +/- 0.08 in the study group and 0.78 +/- 0.06 in the control group (p < 0.001).
      The mean waist to height ratio (WHtR) was 0.62 +/- 0.07 in the study group and
      0.48 +/- 0.04 in the control group (p < 0.001). Waist derived measures were
      superior to BMI in predicting CAD. The unadjusted AUC (95% Confidence Interval)
      was 0.008 (0.006-0.095) for WHtR, 0.001 (0.00 0.002) for waist - hip ratio, and 1
      (0.323-1.766) for body mass index. CONCLUSION: Waist related anthropometric
      measures are important predictors as CAD risk factors among middle-aged and older
      women, as compared to BMI.

PMID- 25755844
TI  - Towards bridging the gap between acid-base transporters and neuronal excitability
      modulation.
AB  - pH homeostasis is a fundamental regulator of the function of the central nervous
      system. Dysfunction of acid-base transporters often results in disturbance of
      neuronal excitability. In a latest issue of Journal of Neuroscience, Jones et al.
      report that increasing intracellular bicarbonate concentration substantially
      stimulates the excitability of pyramidal neurons from mouse hippocampus by
      inhibiting KCNQ potassium channel. The finding shed important new light in
      understanding the molecular mechanism underlying the regulation of neuronal
      excitability by acid-base transporters. 

PMID- 25755845
TI  - COL4A4 gene study of a European population: description of new mutations causing
      autosomal dominant Alport syndrome.
AB  - BACKGROUND: Autosomal forms of Alport syndrome represent 20% of all patients (15%
      recessive and 5% dominant). They are caused by mutations in the COL4A3 and COL4A4
      genes, which encode a-3 and a-4 collagen IV chains of the glomerular basement
      membrane, cochlea and eye. Thin basement membrane nephropathy may affect up to 1%
      of the population. The pattern of inheritance in the 40% of cases is the same as
      autosomal dominant Alport syndrome: heterozygous mutations in these genes. The
      aim of this study is to detect new pathogenic mutations in the COL4A4 gene in the
      patients previously diagnosed with autosomal Alport syndrome and thin basement
      membrane nephropathy in our hospital. METHODS: We conducted a clinical and
      genetic study in eleven patients belonging to six unrelated families with
      aforementioned clinical symptoms and a negative study of COL4A3 gene. The
      molecular study was made by conformation of sensitive gel electrophoresis (CSGE)
      and direct sequencing of the fragments that show an altered electrophoretic
      migration pattern. RESULTS: We found two pathogenic mutations, not yet described:
      IVS3 + 1G > C is a replacement of Guanine to Cytosine in position +1 of intron 3,
      in the splicing region, which leads to a pathogenic mutation. c.4267C > T;
      p.P1423S is a missense mutation, also considered pathogenic. We also found seven
      new polymorphisms. CONCLUSIONS: We describe two new pathogenic mutations,
      responsible for autosomal dominant Alport syndrome. The other families of the
      study were undiagnosed owing to problems in the method employed and the
      possibility of mutations in other genes, giving rise to other diseases with
      similar symptoms.

PMID- 25755846
TI  - Red blood cell indices and prevalence of hemoglobinopathies and glucose 6
      phosphate dehydrogenase deficiencies in male Tanzanian residents of Dar es
      Salaam.
AB  - Hemoglobinopathies, disorders of hemoglobin structure and production, are one of
      the most common monogenic disorders in humans. Glucose 6 phosphate dehydrogenase
      deficiency (G6PD) is an inherited enzymopathy resulting in increased oxygen
      stress susceptibility of red blood cells. The distributions of these genetic
      traits in populations living in tropical and subtropical regions where malaria
      has been or is still present are thought to result from survival advantage
      against severe life threatening malaria disease. 384 male Tanzanian volunteers
      residing in Dar es Salaam were typed for G6PD, sickle cell disease and alpha
      thalassemia. The most prominent red blood cell polymorphism was heterozygous
      alpha(+)-thalassemia (37.8%), followed by the G6PD(A) deficiency (16.4%),
      heterozygous sickle cell trait (15.9%), G6PD(A-) deficiency (13.5%) and
      homozygous alpha(+)-thalassemia (5.2%). 35%, 45%, 17% and 3% of these volunteers
      were carriers of wild type gene loci, one, two or three of these
      hemoglobinopathies, respectively. We find that using a cut off value of 28.6 pg.
      for mean corpuscular hemoglobin (MCH), heterozygous alpha(+)-thalassemia can be
      predicted with a sensitivity of 84% and specificity of 72% in this male
      population. All subjects carrying homozygous alpha(+)-thalassemia were identified
      based on their MCH value < 28.6 pg. 

PMID- 25755847
TI  - Association of SNPs in GHSR rs292216 and rs509035 on dietary intake in Indonesian
      obese female adolescents.
AB  - BACKGROUND: Obesity has been linked to high dietary intake and low physical
      activity. Studies showed that those factors were not only regulated by
      environment but also by genetic. However, the relationship is less been
      understood in obese children and adolescents. OBJECTIVE: The objective of this
      study was to examine the role of SNPs in GHSR rs292216 and rs509035 on dietary
      intake in obese female adolescents. METHODS: This is an observational study with
      cross sectional design. Respondents were obese female adolescents enrolled from
      obesity screening done in six junior high schools in Yogyakarta. Dietary intake
      was measured using 6 days 24 hours inconsecutive dietary recall. Genotyping of 2
      SNPs from GHSR was done using FRLP-PCR. RESULTS: There were 78 obese female
      adolescents joined this study. We found that no significant association between
      SNPs GHSR and dietary intake (p < 0.05). In addition, a SNP-SNP interaction
      analysis shown there is no difference between combination of GHSR rs292216 and
      rs509035 on dietary intake (p < 0.05). CONCLUSION: We concluded that SNPs on GHSR
      rs292216 and rs509035 were not related to dietary intake in Indonesian obese
      female adolescents. Further study is necessary to investigate the effect of those
      genes on dietary intake in the broader population.

PMID- 25755848
TI  - Screening for the mitochondrial A1555G mutation among Egyptian patients with non
      syndromic, sensorineural hearing loss.
AB  - BACKGROUND & AIM: Hearing loss is the most frequent form of neurosensory deficit
      in humans. Although the majority of hereditary hearing loss is due to nuclear
      gene mutations, it has become clear the significant contribution of mitochondrial
      genes. The first mitochondrial mutation shown to cause non-syndromic hearing loss
      in humans was the A1555G mutation in the small ribosomal RNA gene (12S rRNA). It
      has been detected in hundreds of families of different ethnic backgrounds, making
      it one of the prevalent genetic causes of hearing loss currently identified.
      However, there are major differences between ethnic groups regarding the
      frequency of this mutation. Few studies have been made in Arab countries,
      especially in Egypt. Here we report the prevalence of the mitochondrial mutation
      A1555G among patients with non-syndromic hearing loss (NSHL) and in healthy
      individuals with normal hearing in the Egyptian population. SUBJECTS & METHODS:
      The study was conducted on 97 patients with SNHL and 300 unrelated healthy
      Egyptian individuals, with normal hearing, as normal control subjects. Polymerase
      chain reaction followed by restriction enzyme digestion was used to screen the
      DNA samples of all subjects for the A1555G mutation. RESULTS: Participants
      included 97 cases with SNHL, 46 males and 51 females. Their ages ranged from 1
      month to 65 years with the mean age 6.2 years (SD +/- 8.2). Paternal
      consanguinity was reported in 46% (35/76) of the studied families. The A1555G
      mutation was found in one of the 97 patients (1.3%), while it has not been
      detected in the 300 control samples. CONCLUSION: Our findings indicate that, even
      in absence of exposure to aminoglycosides, the mitochondrial A1555G mutation is
      one of the potential causes of non-syndromic SNHL in the Egyptian population.

PMID- 25755850
TI  - Transcriptomics in the tropics: Total RNA-based profiling of Costa Rican
      bromeliad-associated communities.
AB  - RNA-Seq was used to examine the microbial, eukaryotic, and viral communities in
      water catchments ('tanks') formed by tropical bromeliads from Costa Rica. In
      total, transcripts with taxonomic affiliation to a wide array of bacteria,
      archaea, and eukaryotes, were observed, as well as RNA-viruses that appeared
      related to the specific presence of eukaryotes. Bacteria from 25 phyla appeared
      to comprise the majority of transcripts in one tank (Wg24), compared to only 14
      phyla in the other (Wg25). Conversely, eukaryotes from only 16 classes comprised
      the majority of transcripts in Wg24, compared to 24 classes in the Wg25,
      revealing a greater eukaryote diversity in the latter. Given that these
      bromeliads had tanks of similar size (i.e. vertical oxygen gradient), and were
      neighboring with presumed similar light regime and acquisition of leaf litter
      through-fall, it is possible that pH was the factor governing these differences
      in bacterial and eukaryotic communities (Wg24 had a tank pH of 3.6 and Wg25 had a
      tank pH of 6.2). Archaeal diversity was similar in both tanks, represented by 7
      orders, with the exception of Methanocellales transcripts uniquely recovered from
      Wg25. Based on measures of FPKG (fragments mapped per kilobase of gene length),
      genes involved in methanogenesis, in addition to a spirochaete flagellin gene,
      were among those most highly expressed in Wg25. Conversely, aldehyde
      dehydrogenase and monosaccharide-binding protein were among genes most highly
      expressed in Wg24. The ability to observe specific presence of insect, plant, and
      fungi-associated RNA-viruses was unexpected. As with other techniques, there are
      inherent biases in the use of RNA-Seq, however, these data suggest the
      possibility of understanding the entire community, including ecological
      interactions, via simultaneous analysis of microbial, eukaryotic, and viral
      transcripts. 

PMID- 25755849
TI  - Resection of borderline resectable pancreatic cancer after neoadjuvant
      chemoradiation does not depend on improved radiographic appearance of tumor
      vessel relationships.
AB  - OBJECTIVE: Neoadjuvant therapy increases rates of margin-negative resection of
      borderline resectable pancreatic ductal adenocarcinoma (BL-PDAC). Criteria for BL
      PDAC resection following neoadjuvant chemotherapy and radiation therapy (NCRT)
      have not been clearly defined. METHODS: Fifty consecutive patients with BL-PDAC
      who received NCRT from 2007 to 2012 were identified. Computed tomography (CT)
      scans pre- and post-treatment were centrally reviewed. RESULTS: Twenty-nine
      patients (58 %) underwent resection following NCRT, while 21 (42 %) remained
      unresected. Patients selected for and successfully undergoing resection were more
      likely to have better performance status and absence of the following features on
      pre- and post-treatment CT: superior mesenteric vein/portal vein encasement,
      superior mesenteric artery involvement, tumor involvement of two or more vessels,
      and questionable/overt metastases (all p <0.05). Tumor volume and degree of tumor
      vessel involvement did not significantly change in both groups after NCRT (all p
      > 0.05). The median overall survival was 22.9 months in resected versus 13.0
      months in unresected patients (p < 0.001). Of patients undergoing resection, 93 %
      were margin-negative, 72 % were node-negative, and 54 % demonstrated moderate
      pathologic response to NCRT. CONCLUSION: Apparent radiographic extent of vascular
      involvement does not change significantly after NCRT. Patients without metastatic
      disease should be chosen for surgical exploration based on adequate performance
      status and lack of disease progression.

PMID- 25755851
TI  - School nutrition program; prevention of obesity and Fatty liver in children.

PMID- 25755852
TI  - What is the best available evidence for using homeopathy in patients with
      intellectual disabilities?
AB  - OBJECTIVE: The debate about the effectiveness of homeopathy hits the headlines
      from time to time. Reported evidences for the role of homeopathy in psychiatric
      illness relevant to people with intellectual disabilities are patchy and
      inconsistent. In this review we summarize the best available evidence for the use
      of homeopathy to treat the psychiatric disorders common in this population.
      METHODS: Systematic literature review was conducted through February 2012 to July
      2012 in AMED, CINHAL, BNI, EMBASE, MEDLINE, PSYCHINFO and GOOGLE SCHOLAR. In the
      next steps thirty eight homeopathic associations were contacted and a top-up
      literature search was done on Scopus and World of Science databases till March
      2014. Twelve relevant clinical trials were identified and included in this study.
      The quality of each trial was assessed by the Oxford quality scoring system
      (Known as Jadad score) as well as subjective review by two reviewers
      independently (good versus poor). Findings : The largest body of evidence
      pertained to the use of homeopathy in the treatment of attention deficit
      hyperactivity disorder (ADHD). There is heterogeneity in the quality of trials
      and also the outcome of studies but overall our findings suggest some potential
      for using homeopathy in ADHD. Current evidences do not support the use of
      homeopathy for treatment of speech and language difficulties. There was only one
      trial concerning the use of homeopathy in Autistic Spectrum Disorder. This was of
      a poor quality and unable to provide any recommendation. CONCLUSION: Whilst
      acknowledging the risk of publication and language bias in our study, the
      currently available evidences are neither conclusive nor comprehensive enough to
      give us a clear picture for the use of homeopathy in patients with intellectual
      disabilities. There are large gaps in the body of evidence concerning the role of
      homeopathy in the treatment of common disorders in intellectual disability, such
      as autism, challenging behavior or developmental arrest in childhood.

PMID- 25755853
TI  - Management of spasticity in children with cerebral palsy.
AB  - Cerebral palsy is the most common cause of spasticity and physical disability in
      children and spasticity is one of the commonest problems in those with
      neurological disease. The management of spasticity in children with cerebral
      palsy requires a multidisciplinary effort and should be started as early as
      possible. There are a number of treatments available for the management of
      spasticity. This article reviews the variety of options available for the
      clinical management of spasticity. 

PMID- 25755854
TI  - Treatment of cutaneous injuries of neonates induced by drug extravasation with
      hyaluronidase and hirudoid.
AB  - OBJECTIVE: To analyze the effects of hyaluronidase and hirudoid treatment on drug
      extravasation in neonates. METHODS: The medical records of 13 neonates with drug
      extravasation treated with hyaluronidase and hirudoid between August 1(st), 2010
      and May 1(st), 2012 were analyzed retrospectively. The treatment procedure for
      drug extravasation adhered to the protocol in neonatal department. The
      information including age, sex, weight, diagnosis, size of affected area, site of
      extravasation and treatment was collected. Findings : The extravasation injuries
      alleviated and the symptoms improved after treatment, no adverse drug effects
      were reported with use of hyaluronidase and hirudoid. CONCLUSION: The treatment
      appeared to be beneficial in the management of extravasations of various
      medications in neonates and may be useful in reducing the severity of cutaneous
      toxicosis. However, further studies with large samples are still needed to assess
      the effectiveness and safety of hyaluronidase and hirudoid.

PMID- 25755855
TI  - Distribution and Protective Role of HLAB40 in Iranian Patients with Kawasaki
      Disease; a Report from Southern Iran.
AB  - OBJECTIVE: Kawasaki disease (KD) clinically presents as a systemic vasculitis
      syndrome with significant cardiovascular involvement. With different incidence
      among different ethnic groups, the role of certain human leukocyte antigens and
      their products has been considered as a crucial predisposing factor in the immune
      responses in this disease. METHODS: We determined the distribution of human
      leukocyte antigens type B for 90 Iranian patients with Kawasaki disease in order
      to evaluate a possible association between these antigens and this disease in our
      area. We used the polymerase chain reaction (PCR) sequence specific primers (PCR
      SSP) technique for antigen typing. Distribution of these antigens for 89 healthy
      Iranians used as control. Findings : While 7 (3.9%) of our patients were positive
      for human leukocyte antigen type B 40(*), there were 18 (10.1%) subjects from the
      control group who had this antigen with statistically significant difference
      between patients and control group (CI= 95%, RR=1.15 and P= 0.02). Data were
      analyzed by Pearson chi-square test and Fisher's exact test. SPSS version 15 was
      used for statistical analysis and a P value less than 0.05 considered
      statistically significant CONCLUSION: The presence of higher frequency of allele
      type-B40(*) in the control group may represent a protective role for this antigen
      with resultant decreased susceptibility to KD in our area.

PMID- 25755856
TI  - Morbidity and Mortality in Iranian Children with Juvenile Systemic Lupus
      erythematosus.
AB  - OBJECTIVE: Juvenile systemic lupus erythematosus (JSLE) is a common rheumatologic
      disorder that involves multi organ systems. Prognosis of lupus in children may be
      poorer than in adults. In this study, we determined mortality and morbidity rates
      in the pediatric SLE in Iran. METHODS: In a cross sectional study, we evaluated
      120 children with SLE who had registered in our pediatric rheumatology database
      within 2004-2010. Data including sex, age, remission, age at the time of
      diagnosis, age at the time of study, various types of organ involvement,
      mortality and remission were extracted from this database. Findings : From 120
      cases, 77% (92 cases) were females and 23% (28 cases) males (F:M=3.3). Mean
      follow up period was 56+/-32 months and mean age at the time of manifesting
      disease 10.34+/-2.9 years. Mortality rate was 10% (12 cases) in our
      investigation. Musculoskeletal involvement showed significant difference between
      various age groups (P<0.01), that was more frequent in group of 7 years and
      older. Frequency of oral ulcer and ophthalmic involvement in boys was
      significantly higher than in girls (P<0.05). Frequency of cardiovascular
      involvement (P<0.01) and renal involvement (P<0.01) was significantly higher in
      the patients who had no remission. There was a significant association between
      mortality rate and cardiac (P<0.02, OR=4.9), pulmonary (P<0.01, OR=10.167) and
      liver (P<0.05, OR=1.19) involvement. CONCLUSION: In our investigation 1-year
      survival rate was 97% and 5-year survival rate 89%. Liver, cardiac and pulmonary
      involvements have an association with higher mortality in JSLE patients.

PMID- 25755857
TI  - The Expression and Prognostic Impact of CD95 Death Receptor and CD20, CD34 and
      CD44 Differentiation Markers in Pediatric Acute Lymphoblastic Leukemia.
AB  - OBJECTIVE: This study investigated the expression and prognostic significance of
      the CD95 death receptor and CD20, a B cell-lineage associated marker, along with
      CD34 and CD44 non-lineage associated molecules in Iranian children with acute
      lymphoblastic leukemia (ALL). METHODS: We performed immunophenotyping for
      expressions of the molecules in blood samples from children diagnosed with ALL by
      using a panel of monoclonal antibodies for flow cytometry analysis. The
      expression of markers was evaluated in relation to clinical and paraclinical
      features as well as response to treatment in the patients. Findings : CD95 showed
      a higher expression in T-ALL compared to B-ALL (P<0.001). Analysis of the
      clinical and laboratory findings at diagnosis in the group of B-ALL patients
      revealed an association between CD95 expression with lower white blood cell (WBC)
      numbers and bone marrow blasts (P<0.05). We detected a positive correlation
      between the expressions of CD95 and CD44 (r=0.445, P<0.01) in B-ALL patients.
      There was an association between CD20 expression and several poor prognostic
      factors that included increased extramedullary involvement (EMI) and decreased
      platelet numbers (P<0.008). The mean expression of CD34 in B-ALL was higher than
      T-ALL (P=0.004). At follow-up, complete remission duration (CRD) and survival
      duration did not significantly differ between patients who were positive or
      negative for each marker. CONCLUSION: Association of the studied molecules with
      several prognostic factors implies the significance of CD95 molecule as favorable
      and CD20 as unfavorable prognostic markers for childhood ALL.

PMID- 25755858
TI  - Consequences of delayed diagnosis in treatment of retinoblastoma.
AB  - OBJECTIVE: One of the primary factors in managing patients with retinoblastoma is
      early diagnosis. The main idea of this study was to recognize the consequences of
      delay in diagnosis on therapy of the disease. METHODS: A retrospective review of
      all children with proven retinoblastoma, who had presented to MAHAK hospital in
      Tehran, from April 2007 to Dec 2011, was performed. Grouping of intraocular
      tumors was applied as A to E according to International Classification of
      Retinoblastoma. Findings : There were 157 (91 boys) children eligible for study.
      The mean age was 1.21+/-0.11 years with average delay in diagnosis of 3.4+/-0.53
      months. Classification of D group in both unilateral (93 patients) and bilateral
      tumors was the largest category. A significant relation (P=0.05) between delayed
      diagnosis time and tumor grouping was evident. The most frequent symptoms were
      leukocoria and strabismus. Age was significantly lower in the subgroup of
      bilateral tumors than in unilateral retinoblastomas (0.6+/-0.12 year vs 1.6+/
      0.15 years). The diagnosis was delayed in subgroup of extra ocular retinoblastoma
      more than in intraocular tumors (8.7+/-2.9 months vs 2.9+/-0.52 months).
      CONCLUSION: The authors recommend early referring of suspected cases to
      ophthalmologists and pediatric oncologists and to organize educational programs
      to publisize signs and symptoms of the disease such as leukocoria, strabismus and
      ocular inflammatory disorders through national media. In conclusion, early
      diagnosis of retinoblastoma can be the primary factor in managing the patients as
      the delay in diagnosis accounts for highly advanced disease and poor prognosis.

PMID- 25755859
TI  - Scrub typhus in children at a tertiary hospital in north India: clinical profile
      and complications.
AB  - OBJECTIVE: To study the clinical profile and complications of childhood scrub
      typhus. METHODS: Prospective observational study of 66 children with scrub
      typhus, admitted to a tertiary hospital in north India, during the period between
      January 2011 and December 2012. The diagnosis was confirmed by serology. Findings
      : All children presented with fever. Other common symptoms were vomiting (56%),
      facial swelling (52%), cough (35%), abdominal pain (33%), breathlessness (29%)
      and decreased urine output (29%). High grade fever (>101 (o)F) was recorded in
      91% of children. Other common signs were hepatomegaly, splenomegaly, edema,
      tender lymphadenopathy and hypotension, observed in 82%, 59%, 39%, 38% and 36% of
      cases, respectively. An eschar and a maculopapular rash each were observed in 20%
      of patients. Meningoencephalitis (30.3%), severe thrombocytopenia (27.2%), shock
      (25.8%), acute kidney injury (16.7%) and hepatitis (13.6%) were the most common
      complications observed in these children. Other common complications were acute
      respiratory distress syndrome, respiratory failure requiring ventilation,
      bronchopneumonia and myocarditis. Ninety percent of children became afebrile
      within 48 hours of initiating an appropriate antibiotic. Median time to
      defervescence was 22 hours. The overall mortality rate was 7.5%. Causes of death
      were refractory shock, meningoencephalitis, acute respiratory distress syndrome,
      bronchopneumonia, acute kidney injury and myocarditis. CONCLUSION: Pediatricians
      should keep a high index of suspicion for scrub typhus in any febrile child
      having a maculopapular rash, hepatosplenomegaly, tender lymphadenopathy,
      thrombocytopenia and features suggestive of capillary leak. Pending serological
      confirmation, empirical therapy with doxycycline or azithromycin should be
      started, as delay in treatment would result in life threatening complications.

PMID- 25755860
TI  - Risk factors for neonatal mortality at the yaounde gynaeco-obstetric and
      pediatric hospital, cameroon.
AB  - OBJECTIVE: Neonatal mortality is a major health problem in sub-Saharan Africa and
      the risk factors are not well established. The objective of this study was to
      determine the risk factors for neonatal mortality at the Yaounde Gynaeco
      Obstetric and Pediatric Hospital. METHODS: We conducted a retrospective and
      analytic case-control study from the medical records of newborns admitted at the
      neonatal unit of this hospital between 1(st) March 2003 and 31(st) December 2012.
      850 subjects were enrolled; that is 425 cases and 425 controls. Findings : The
      intra-hospital neonatal mortality rate was 9.83%. The main causes of neonatal
      mortality were in descending order: neonatal sepsis (60.2%), complications from
      prematurity (42.6%), birth asphyxia (37.4%), and congenital malformations
      (11.8%).The most prominent risk factors for neonatal mortality after multivariate
      analysis with logistic regression were: prolonged membrane rupture (OR: 3.8719,
      95% CI: 2.3619-6.3471; P=0.0000), low birth weight (OR: 1.6240, 95% CI: 1.0108
      2.6091; P=0.0450), Apgar score less than 7 at the 5th minute (OR: 6.8979, 95% CI:
      4.0709-11.6883; P=0.0000), and congenital malformations (OR: 4.3307, 95% CI:
      1.6120-11.6347; P=0.0037). Delivery by cesarean section (OR: 0.2644, 95% CI:
      0.1478-0.4732; P=0.0000) and being born in this hospital (OR: 0.4409;95% CI:
      0.2566-0.7576; P=0.0030) were protective. CONCLUSION: Neonatal mortality was
      influenced by both maternal and neonatal factors. This could be reduced through
      sensitization of pregnant women on the need of good quality antenatal visits, and
      capacitating the health personnel on the adequate management of high risk
      neonates.

PMID- 25755861
TI  - Evaluation of selenium levels and mean platelet volume in patients with simple
      febrile convulsion.
AB  - OBJECTIVE: This study aimed to evaluate serum selenium levels and mean platelet
      volume in children who experience simple febrile convulsion. METHODS: The study
      comprised 42 patients diagnosed with simple febrile convulsions and a control
      group of 30 healthy children. Blood samples were taken following a febrile
      convulsion. Selenium levels in the serum of both the patients and control
      subjects were measured with the hydride formation method on an atomic absorption
      spectrometry device and mean platelet volume was evaluated. FINDINGS: When the
      mean values of the febrile convulsion patients were compared with those of the
      control group, the mean selenium levels and thrombocyte count were found to be
      statistically significantly low (P=0.002, P=0.01 respectively) and the mean
      platelet volume values were statistically significantly high (P=0.002).
      CONCLUSION: While low serum selenium levels cause the onset of a febrile seizure
      in patients with simple febrile convulsion, it is thought that the increased mean
      platelet volume shows infection activity causing febrile convulsion.

PMID- 25755862
TI  - The cosmetic results of a simple method for repairing preputial skin defect in
      hypospadias.
AB  - OBJECTIVE: Hypospadias is a common birth defect of the penis. Besides the
      abnormal position of the urethral opening, there is usually a ventral preputial
      defect with preputial redundancy in dorsal shaft. There are many flap procedures
      for correcting this defect. Here, we present our experience of skin coverage
      procedure with better cosmetic results. METHODS: It is a prospective study on
      patients with mid-shaft to glandular hypospadias operated from June 2008 to
      December 2012. The operations were performed by one surgeon in two hospitals and
      the cosmetic results were evaluated by the surgeon, parents, and another
      pediatric surgeon by a satisfaction questionnaire. In this procedure, inner
      prepuce was incised curvilinearly, remaining 5 mm in medial and 8 mm in lateral
      aspects of the inner prepuce. For skin repair, dorsal flaps were approximated in
      midline along median raphe. FINDINGS: Sixty-three patients with mean age of
      25.75+/-8.46 (7-93) months were followed up for 7.06+/-3.34 (2-15( months. There
      were 4 complications. The overall satisfaction with penile skin coverage was
      93.7% for parents and 98.4% for surgeons. Patients' age and primary site of
      meatus had a significant correlation with cosmetic results (P<0.05), while
      urethroplasty techniques and post-operative complications were not significant.
      CONCLUSION: Reapproximation of dorsal flaps in midline is a simple method and can
      be used in most cases of uncomplicated primary hypospadias. By this technique a
      more normal appearance can be achieved.

PMID- 25755864
TI  - Can procalcitonin reduce unnecessary voiding cystoureterography in children with
      first febrile urinary tract infection?
AB  - OBJECTIVE: Recently, new predictors of vesicoureteral reflux (VUR) in children
      with a first febrile UTI such as Procalcitonin (PCT) were introduced as selective
      approaches for cystography. This study wants to show the capability of PCT in
      predicting presence of VUR at the first febrile UTI in children. METHODS:
      Patients between 1 month and 15 years of age with febrile UTI were included in
      this prospective study. PCT values were measured through a semi-quantitative
      method in four grades comprising values less than 0.5, 0.5-2.0, 2.0-10.0 and
      above 10.0 ng/ml. The independence of PCT levels in predicting VUR were assessed
      after adjustment for all potential confounders using a logistic-regression model.
      FINDINGS: A total of 68 patients, 54 (79.4%) girls and 14 (20.6%) boys were
      evaluated. PCT level demonstrated a significant difference between patients with
      positive VUR and those with negative VUR (P=0.012). To calculate the independent
      factors that may predict the presence of VUR, all included variables were
      adjusted for age and sex. Results of logistic regression showed that a PCT level
      between 2.0 and 10.0 ng/mL could independently predict presence of VUR (Odds
      ratio=6.11, CI 95%= 1.22-30.77, P=0.03). CONCLUSION: Our finding in this study
      showed that readily available semi-quantitative measures for PCT are feasible for
      detecting patients with VUR. We suggest that in semi-quantitative measurements of
      PCT, levels between 2.0 and 10.0 ng/ml could be an independent predictor of
      positive VUR.

PMID- 25755863
TI  - Epicardial adiposity in children with obesity and metabolic syndrome.
AB  - OBJECTIVE: Obesity increases cardiac diseases by increasing tendency to
      atherosclerosis. Our aim was to define epicardial adipose tissue thickness, and
      its related factors in obese children. METHODS: Total of 94 patients were divided
      into obesity with metabolic syndrome (MS) (n=30), obesity without MS (n=33), and
      control (n=31) groups. Auxological values with fasting glucose, fasting insulin,
      alanine transaminase, serum lipid levels, and high sensitive C-reactive protein
      levels were evaluated. Epicardial adipose tissue thickness, interventricular
      septum thickness and left ventricular mass were measured by echocardiography.
      FINDINGS: Weight, body mass index, waist circumference, insulin, alanine
      transaminase, and high sensitive C-reactive protein values were markedly higher
      in obesity group when compared with controls (P<0.001). Epicardial adipose tissue
      thickness was 0.64+/-0.23 cm in obesity with MS; 0.60+/-0.20 cm in obesity
      without MS, and 0.27+/-0.12 cm in control group (P<0.001). Interventricular
      septum thickness and left ventricular mass values were markedly high in obesity
      without MS group (P<0.001 and P=0.002). CONCLUSION: Our study has indicated that
      obesity has unfavorable effects on heart starting in the adolescence.

PMID- 25755865
TI  - The effect of high risk pregnancy on duration of neonatal stay in neonatal
      intensive care unit.
AB  - OBJECTIVE: High risk pregnancies increase the risk of neonatal mortality and
      morbidity. In order to identify the influence of pregnancy complications on the
      period of neonatal stay in Neonatal Intensive Care Units (NICUs), an analysis has
      been carried out in our center. METHODS: In a cross-sectional-descriptive
      analytical study, the data including NICU length of stay was gathered from 526
      medical records of neonates. We also assessed their maternal complications such
      as premature rapture of membranes (PROM), urinary tract infection (UTI),
      preeclampsia, oligohydramnios, and twin/triplet pregnancy. Finally we analyzed
      the relation between variables by SPSS statistics software version 19. The level
      of significance was considered P<0.05. FINDINGS: 37 of 526 neonatal medical
      records were excluded. Of the 489 babies hospitalized in NICU for 1 to 54 days;
      28.42% born were preterm, 308 with birth weight <2500 gram and 170 with birth
      weight between 2500 and 4000 gram. There was a significant relation between
      length of neonatal NICU stay and maternal PROM (P=0.001), preeclampsia (P=0.01),
      UTI (P=0.02), multiple gestation (P=0.03), and oligohydramnios (P=0.003). We
      found a positive correlation between numbers of gestation and length of NICU stay
      (P=0.03). A positive correlation existed between neonatal complication and length
      of NICU stay (P<0.001). CONCLUSION: By increasing maternal health level and
      prenatal care services, neonatal outcome can be improved and length of stay in
      NICUs decreased.

PMID- 25755866
TI  - Does gluten-free diet protect children with celiac disease from low bone density?
AB  - OBJECTIVE: We aimed to assess the effect and duration of gluten-free diet on bone
      health in children with celiac disease in our study. METHODS: Sixty three
      patients with celiac disease (CD) formed the study group. They were divided into
      two subgroups according to their dietary compliance. Bone mineral density (BMD)
      values of the patients at two and five years of gluten-free diet (GFD) were
      determined. Findings : The relationship between BMD and compliance to GFD was
      found to be statistically significant (P<0.01). BMD z-scores were increased
      (0.12+/-0.15 and 0.10+/-0.14 units respectively) (P<0.01). The patients in group
      1 and 2 had mean -1.18+/-0.83 and -2.06+/-0.73 z-scores in the first DXA. In the
      second DXA, these values were -1.10+/-0.73 and-1.94+/-0.93 respectively.
      CONCLUSION: Dietary compliance is important for bone health, and the time needed
      to normalize the BMD is not known. Patients with positive anti-endomysium
      antibody (EMA), poor dietary history and history of bone pain should be evaluated
      with DXA during follow-up.

PMID- 25755867
TI  - The enhanced ability of peripheral mononuclear cells differentiating into neural
      cells in term infants with good improvement suffering from severe hypoxic
      ischemic encephalopathy.
AB  - OBJECTIVE: It has been found that asphyxia influences proliferation and
      differentiation of brain neural stem cells in newborn animal models, and that
      peripheral blood stem cells play an important role in repairing brain damage. But
      it has not been reported yet whether asphyxia influences peripheral blood stem
      cells differentiating into neural cells, and whether with the progress of the
      disease there is a change of peripheral blood stem cells differentiating into
      neural cells in newborns with hypoxic ischemic encephalopathy (HIE). METHODS:
      Fifty term HIE infants were enrolled in research from March, 2007 to March, 2010.
      There were 10 cases of the severe HIE patients with good improvement, the severe
      HIE patients with poor improvement, the moderate HIE patients, the mild HIE
      patients and the controls, respectively. The peripheral mononuclear cells
      collected within 24 hours and on 7th day after birth were cultured in vitro for
      10 days to differentiate into neural cells. The induced nestin positive cells
      were identified with Immunohistochemistry and counted. Findings : Within 24 hours
      after birth, there were no difference of induced nestin positive cells among the
      severe HIE patients with good improvement (68.99+/-7.85), the severe HIE patients
      with poor improvement (71.43+/-6.88), the moderate HIE patients (73.34+/-6.46),
      the mild HIE patients (70.46+/-6.66) and the controls (71.13+/-7.19, F=0.51,
      P=0.7). In the severe HIE patients with obvious improvement, the induced nestin
      positive cells from 7th day peripheral blood mononuclear cells (94.50+/-15.57)
      increased markedly compared with that within 24 hours (68.99+/-7.85, t=4.66,
      P<0.001), and were higher than the induced nestin positive cells from 7(th) day
      peripheral blood mononuclear cells in the severe HIE patients with no obvious
      improvement (94.50+/-15.57 vs 69.48+/-5.32, t=4.62, P<0.001). CONCLUSION: The
      ability of peripheral mononuclear cells differentiating into neural cells in term
      infants with good improvement suffering from severe HIE was enhanced, which may
      suggest possible relationship between the brain repair and the peripheral stem
      cells.

PMID- 25755868
TI  - Pediatric Germ Cell Tumors; A 10-year Experience.
AB  - OBJECTIVE: The aim of this study was to evaluate the outcome of germ cell tumors
      in patients admitted to our center during a ten year period. METHODS: In a
      retrospective descriptive study, patients with the pathological diagnosis of germ
      cell tumor (GCT) were included. All records were evaluated and patients followed
      by personal visit in clinic or phone call. Data regarding age, sex, tumor site,
      bio-chemical assay, pathology, treatment and outcomes were gathered. For
      qualitative variables we computed frequency and percentage and for quantitative
      variables, mean and standard deviation. Survival analysis was performed using
      Kaplan-Meier. All statistical analyses were performed by SPSS version16.0.
      Findings : Forty four patients consisted of 32 girls (72.7%) and 12 boys (27.3%).
      Their median age was 23 months. The most common pathological tumor types were 18
      (40.9%) mature teratomas and 14 (31.8%) yolk sac tumors. Extra gonadal tumors
      were more prevalent (32 cases) and consisted of 21 (47.7%) sacrcoccygeal, 7
      (15.9%) retroperitoneal, 2 (4.4%) mediastinal and 2 (4.4%) cervical tumors. In
      gonadal tumors 9 patients had ovarian and 3 patients testicular involvement.
      Staging at the time of diagnosis revealed stage one in 23 (52.3%) cases. All
      patients were treated surgically and the most common procedure was total
      resection in 41 (93.2%) patients. Fifteen (34.1%) patients received chemotherapy.
      In follow-up 31 (77.5%) patients were in complete remission, 9 (22.5%) had died,
      and 4 cases did not appear to follow-up visits. The median survival was 16 months
      (IQR 4-49 months). The highest mortality rate was found in patients with yolk sac
      tumors (8 of 13 cases). CONCLUSION: The patients with extra-gonadal GCT and a
      high AFP level have the worst prognosis and lower survival rate. Combination of
      surgery and chemotherapy can lead to a better prognosis.

PMID- 25755869
TI  - Neonatal Lupus erythematosus Following Rheumatoid Arthritis: Case Report and
      Literature Review.
AB  - BACKGROUND: Neonatal lupus erythematosus (NLE) is a transient autoimmune disease
      of developing fetus and neonate in mothers with systemic lupus erythematosus
      (SLE). In this report we introduce an infant with NLE whose mother had rheumatoid
      arthritis. CASE PRESENTATION: Our case was a 40 day old male infant with discoid
      like and annular skin lesions over forehead and neck, irritability and low grade
      fever. There was a history of prematurity due to preeclampsia. There was no
      cytopenia or cardiac involvement but liver enzymes were more than 5-fold
      increased. FANA, Anti Ro and La were negative. The mother had a history of un
      controlled rheumatoid arthritis for 12 years with deformity in metacarpal and PIP
      and ulnar deviation in hands. FANA=1/640 and anti-SSB/La was positive in the
      mother but there was no other clinical and paraclinical sign of SLE. Without any
      treatment and during months, the skin and mucosal lesions gradually disappeared
      without any scar and liver enzymes reached the normal level. After 6 months
      follow up, he was symptom free with normal growth and development. CONCLUSION: We
      recommend to check anti SSA/Ro and anti SSB/La antibodies in all pregnant women
      with connective tissue diseases to prevent life-threatening involvement of the
      infant.

PMID- 25755870
TI  - A newborn with omphalocele and umbilical cord cyst: an interesting entity.

PMID- 25755871
TI  - Neonatal suppurative parotitis: a case report.

PMID- 25755872
TI  - Does maternal quality of life influence breastfeeding difficulties?

PMID- 25755873
TI  - Sudden intrauterine unexpected fetal death syndrome and sudden infant death
      syndrome.

PMID- 25755874
TI  - Complex odontomas hampering eruption of permanent tooth.

PMID- 25755875
TI  - Current preventative and health promotional care offered to patients by
      chiropractors in the United Kingdom: a survey.
AB  - BACKGROUND: With increasing morbidity and mortality attributable to non
      communicable disease, primary healthcare providers are urged to increasingly
      support people in making healthy lifestyle choices. Many chronic physical
      diseases associated with lifestyle behaviours have been linked to
      neuromusculoskeletal disorders and pain. Chiropractors, as primary healthcare
      professionals, are in a position to provide preventative and promotional
      healthcare to patients, however, it is unknown to what extent such care is
      provided, particularly in the United Kingdom (UK). METHOD: This study was a cross
      sectional online questionnaire distributed to four UK chiropractic associations.
      The responses were collected over a period of two months from March 26th 2012 to
      May 25th 2012. Descriptive analyses were performed to identify the trends in
      current practice of chiropractors in the UK. Additionally, subgroup analyses of
      all items were performed using Pearson Chi-Square tests to determine
      statistically significant differences between respondents based on gender, years
      in practice, educational institution and association membership. RESULTS: Of the
      2,448 members in the four participating associations, 509 chiropractors
      (approximately 21%) completed the survey. The great majority of UK chiropractors
      surveyed report evaluating and monitoring patients in regards to posture (97.1%),
      inactivity/overactivity (90.8%) and movement patterns (88.6%). Slightly fewer
      provide this type of care for psychosocial stress (82.3%), nutrition (74.1%) and
      disturbed sleep (72.9%). Still fewer do so for smoking (60.7%) and over
      consumption of alcohol (56.4%). Verbal advice given by the chiropractor was
      reported as the most successful resource to encourage positive lifestyle changes
      as reported by 68.8% of respondents. Goal-setting is utilised by 70.7% to 80.4%
      of respondents concerning physical fitness issues. For all other lifestyle
      issues, goal-setting is used by approximately two-fifths (41.7%) or less. For
      smoking and over-consumption of alcohol, a mere one-fifth (20.0% and 20.6%
      respectively) of the responding chiropractors set goals. CONCLUSIONS: UK
      chiropractors are participating in promoting positive lifestyle changes in areas
      common to preventative healthcare and health promotion areas; however, more can
      be done, particularly in the areas of smoking and over-consumption of alcohol. In
      addition, goal-setting to support patient-provider relationships should be more
      widespread, potentially increasing the utility of such valuable advice and
      resources.

PMID- 25755877
TI  - Presenting prevalence and management of psychosocial problems in primary care in
      Flanders.
AB  - BACKGROUND: Psychosocial problems are widespread but reliable data about
      management are sparse. An overall view is missing and there is a need for a wider
      framework to include the data available in health care and welfare practice,
      databases and research output. The question under scope is: how are psychosocial
      problems presented and handled in primary care in Flanders? METHODS: A mixed
      method was used. Using a 'fishbone diagram' (1) we obtained a basic structure to
      visualize the main (problem) areas and challenges. A literature study (2) and
      semi-structured interviews with health care and welfare professionals in primary
      care (3) were performed. Finally, two interdisciplinary focus groups were
      organized (4). RESULTS: In Flanders, there is no tradition of multidisciplinary
      psychosocial research in primary care causing a lack of integrated data. Data
      only exist within disciplines without transdisciplinarity. The data are difficult
      to interpret due to different labeling and registration processes between
      disciplines and settings. However, we can find some general trends: assistance to
      patients with psychosocial problems is based on what can be offered, rather than
      on patient needs; drug treatment remains popular; referral of patients within
      primary care or to secondary care does not seem to be obvious. Among all
      disciplines, there is a great need for more collaboration and considerable
      advantages are to be expected from the growing emergence of multidisciplinary
      practices; multiculturalism appears to take an increasingly important place
      within primary care in Flanders and has implications for the care offered; and
      treatment effectiveness in psychosocial problems seems to be more related to the
      person of the caregiver than to a specific discipline, theory or type of
      treatment. CONCLUSIONS: Based on our results, we strongly advise stimulation and
      organization of integrated (multidisciplinary) research regarding psychosocial
      problems in primary care and a more consistent registration by the agencies in
      primary care.

PMID- 25755876
TI  - The H2S-releasing naproxen derivative, ATB-346, inhibits alveolar bone loss and
      inflammation in rats with ligature-induced periodontitis.
AB  - BACKGROUND: In experimental periodontitis, non-steroidal antiinflammatory drugs
      (NSAIDs) effectively inhibit the resultant alveolar bone loss. However, their
      deleterious gastric effects, observed in both animals and humans, dramatically
      limit their long-term use. It has been proven that the addition of a hydrogen
      sulfide (H2S)-releasing moiety to classical NSAID structures results in
      antiinflammatory compounds with improved gastric safeness. In this way, we
      decided to compare the effects of naproxen with its H2S-releasing derivative ATB
      346 on ligature-induced periodontitis in rats. METHODS: Male Holtzman rats had a
      cotton ligature placed subgingivally around the lower right first molar during 7
      days. During this period, groups of animals were daily treated with Na2S (a
      spontaneous H2S donor) or equimolar oral doses of naproxen (10 mg/kg) or ATB-346
      (16 mg/kg). The mandibles were finally collected for histological analysis,
      radiographical measurements of alveolar bone loss and micro-computed tomography
      (MUCT) analysis. Interleukin (IL)-1beta, IL-6 and IL-10 were quantified in
      gingiva samples, and the stomachs were also collected for scoring of tissue
      damage and measurement of myeloperoxidase (MPO, a marker of granulocyte
      infiltration). RESULTS: Ligature-induced bone loss was significantly inhibited by
      all the treatments, although only ATB-346 treatment resulted in significant
      inhibition of bone defect and other histological characteristics (such as
      flatness of the gingival epithelium, chronic inflammatory cell infiltration and
      loss of connective tissue in the gingival papillae). Both naproxen and ATB-346
      inhibited the increase of gingival IL-1beta and IL-6 secondary to periodontitis,
      but IL-10 was unaffected. Significant damage and increased MPO contents were only
      found in the stomachs of the naproxen-treated animals. CONCLUSION: The H2S
      releasing moiety in the ATB-346 compound not only does not impair the effects of
      the parent naproxen on periodontitis, but also improves bone quality and prevents
      the gastric mucosa damage due to prostaglandin inhibition, thus configuring a
      potentially new adjuvant therapy for periodontal diseases.

PMID- 25755878
TI  - Large testicular adrenal rest tumours in a patient with congenital adrenal
      hyperplasia.
AB  - Testicular adrenal rest tumours (TARTs) are benign ACTH-dependent tumours that
      occur in males with congenital adrenal hyperplasia (CAH) and if left untreated
      can destroy testicular tissue. Corticosteroid suppressive treatment could result
      in the regression of these testicular tumours. We present a patient with
      bilateral large TARTs as a consequence of poor compliance to treatment and follow
      up for his CAH, who consequently had to have bilateral orchidectomies and
      prosthesis replacement. LEARNING POINTS: TARTs are frequently seen in males with
      CAH, and can be misdiagnosed as primary testicular cancer.Patient compliance to
      treatment and follow-up are necessary to reduce the risk of testicular damage as
      a result of TARTs in patients with CAH.Boys with CAH should have periodic
      ultrasonographic screening from before adolescent age for early detection of
      TARTs.Regular monitoring of renin, 17-hydroxyprogesterone and androgens levels is
      required to assess corticosteroid suppressive treatment.Patients with CAH should
      be offered psychological support and information concerning CAH support groups.

PMID- 25755879
TI  - Recurrent pituitary apoplexy due to two successive neoplasms presenting with
      ocular paresis and epistaxis.
AB  - A case of recurrent pituitary apoplexy is described in a 72-year-old man who
      initially presented with haemorrhage in a non-functioning pituitary adenoma. Five
      years later, he re-presented with a severe pituitary haemorrhage in an enlarging
      sellar mass invading both cavernous sinuses causing epistaxis and bilateral
      ocular paresis. Subsequent histology was consistent with a sellar malignant
      spindle and round cell neoplasm. Multiple pituitary tumours have previously been
      reported to coexist in the same individual, but to our knowledge this is the only
      case where two pathologically distinct pituitary neoplasms have sequentially
      arisen in a single patient. This case is also notable with respect to the
      progressive ocular paresis, including bilateral abducens nerve palsies, and the
      presentation with epistaxis. LEARNING POINTS: Ocular paresis in pituitary
      apoplexy can result from tumour infiltration of nerves, or by indirect
      compression via increased intrasellar pressure.Epistaxis is a very rare
      presentation of a pituitary lesion.Epistaxis more commonly occurs following trans
      sphenoidal surgery, and can be delayed.

PMID- 25755880
TI  - Prolonged life-threatening hypoglycaemia following dose escalation of octreotide
      LAR in a patient with malignant polysecreting pancreatic neuroendocrine tumour.
AB  - This paper details the case of a 77-year-old male with refractory hypoglycaemia
      due to inoperable metastatic pancreatic neuroendocrine tumour (pNET) co-secreting
      insulin and gastrin. Multiple medical therapies were trialled with limited
      success, and we describe the complications experienced by our patient.
      Somatostatin analogues can ameliorate hypoglycaemia and may have tumour
      stabilising effects; however, in our case resulted in paradoxical worsening of
      hypoglycaemia. This rendered our patient hospital dependent for glycaemic support
      including continuous dextrose infusion. Although this is a reported adverse
      effect with initiation of therapy, we describe successful initiation of short
      acting octreotide as an inpatient followed by commencement of long-acting
      octreotide. Hypoglycaemic collapse occurred only after dose titration of long
      acting octreotide. We outline the pitfalls of somatostatin analogue therapy and
      the mechanisms that may contribute to worsening hypoglycaemia. This rare side
      effect cannot be reliably predicted, necessitating close supervision and glucose
      monitoring during therapy. Our patient achieved disease stabilisation and gradual
      resolution of hypoglycaemia with peptide receptor radionuclide therapy (PRRT), an
      emerging therapeutic option for metastatic neuroendocrine tumours with high
      efficacy and low toxicity. We present a brief but comprehensive discussion of
      currently available and novel therapies for insulin secreting pNETs. LEARNING
      POINTS: Hypoglycaemia due to malignant insulin secreting pNET is frequently
      severe and may be life-threatening despite supportive therapies.Octreotide can
      ameliorate hypoglycaemia, and may have anti-proliferative and tumour-stabilising
      effects in malignant pNETs that are surgically unresectable.Paradoxical worsening
      of hypoglycaemia may occur with octreotide initiation and dose titration,
      necessitating close supervision and glucose monitoring.PRRT is emerging as a
      therapeutic option with high efficacy and low toxicity.

PMID- 25755881
TI  - Functional parathyroid cyst in a patient with systemic lupus erythematosus: a
      case report.
AB  - Functional parathyroid cysts are a rare cause of primary hyperparathyroidism and
      are often mistaken for thyroid cysts. Systemic lupus erythematosus (SLE) is also
      a very rare cause of hypercalcemia. We report the case of a 62-year-old woman,
      who was diagnosed with SLE 30 years ago, presenting with clinical and biochemical
      features of primary hyperparathyroidism. Laboratory investigation revealed
      increased serum calcium and parathyroid hormone (PTH) levels; neck
      ultrasonography (USG) revealed 40*34*26 mm cystic mass in the left lobe of
      thyroid gland. PTH level in the cysts was >2500 pg/ml, determined by USG-guided
      fine-needle aspiration (FNA). In this case, no evidence for potential pathogenic
      association between parathyroid cyst and SLE was uncovered. However, the
      recognition of this association is very important because the therapeutical
      strategy is completely different. Operative management is usually straightforward
      and alleviates symptoms and any biochemical abnormalities caused by the cyst.
      LEARNING POINTS: Functional parathyroid cysts are the rare cause of primary
      hyperparathyroidism and are often mistaken for thyroid cysts.SLE is also a very
      rare cause of hypercalcemia.Ultrasound-guided FNA of cystic fluid with assay for
      PTH level is an accurate method of differentiating parathyroid cyst from thyroid
      cyst.Appropriate management of functional parathyroid cysts is surgical excision.

PMID- 25755882
TI  - First case of pregnant women bacteraemia and probable early-onset neonatal
      infection due to Aerococcus urinae.

PMID- 25755883
TI  - First report of mecC MRSA in human samples from Austria: molecular
      characteristics and clinical data.
AB  - Reports of mecC methicillin-resistant Staphylococcus aureus (MRSA) strains have
      been published from several European countries. We describe the first six mecC
      MRSA isolates of human origin from Austria and report the application of a rapid
      PCR test. Candidate isolates (n = 295) received between 2009 and 2013 were
      investigated phenotypically by cefoxitin screening and streaking on ChromID MRSA
      plates. The presence of mecC was confirmed in six isolates from blood cultures,
      wound swabs and screening samples of four female and two male patients (age range
      7-89 years) by an in-house PCR method and the new Genspeed MRSA test (Greiner Bio
      One, Kremsmunster, Austria). The mecC MRSA were further characterized by whole
      genome sequencing, multilocus sequence and spa typing. Antimicrobial
      susceptibility testing was performed by Eucast disk-diffusion method and Vitek 2.
      The six mecC MRSA isolates were from two clonal lineages (CC130, including a new
      single-locus variant, and CC599) and four different spa types (t843, t1535,
      t3256, t5930). Analysis for virulence factor genes yielded lukED, eta, etd2 and
      edin-B (CC130 isolates) and tst, lukED, eta and sel (ST599 isolates). The
      Genspeed MRSA test identified mecC in all isolates whereas Vitek 2 failed to
      detect methicillin resistance in one isolate. The strains were susceptible to a
      wide range of non-beta-lactam antibiotics. All patients were successfully treated
      or decolonized. mecC MRSA are present in Austria as colonizers but may also cause
      infections. Thus, laboratories must choose appropriate test methods such as
      cefoxitin screening and confirmation using molecular assays specifically
      targeting mecC. 

PMID- 25755884
TI  - Disseminated Nocardia infection: spontaneous resolution in response to decrease
      of immunosuppression.

PMID- 25755886
TI  - First reported case of Staphylococcus condimenti infection associated with
      catheter-related bacteraemia.
AB  - We report a case of a patient who experienced a catheter-related bloodstream
      infection caused by Staphylococcus condimenti, which was first isolated from soy
      sauce mash. This is the first reported case of human infection. Although blood
      culture isolates and the catheter tip tube did not reveal coagulase or clumping
      factor, false-positive results were obtained from latex agglutination tests for
      clumping factor and protein A due to self-agglutination. Care is needed when
      performing only latex agglutination test without a coagulase test. Further
      studies are needed to determine the pathogenic potential of S. condimenti based
      on appropriate identification. 

PMID- 25755885
TI  - Prevalence and pathogenicity of binary toxin-positive Clostridium difficile
      strains that do not produce toxins A and B.
AB  - Clostridium difficile causes antibiotic-associated diarrhoea and pseudomembranous
      colitis. The main virulence factors of C. difficile are the toxins A (TcdA) and B
      (TcdB). A third toxin, called binary toxin (CDT), can be detected in 17% to 23%
      of strains, but its role in human disease has not been clearly defined. We report
      six independent cases of patients with diarrhoea suspected of having C. difficile
      infection due to strains from toxinotype XI/PCR ribotype 033 or 033-like, an
      unusual toxinotype/PCR ribotype positive for CDT but negative for TcdA and TcdB.
      Four patients were considered truly infected by clinicians and were specifically
      treated with oral metronidazole. One of the cases was identified during a
      prevalence study of A(-)B(-)CDT(+) strains. In this study, we screened a French
      collection of 220 nontoxigenic strains and found only one (0.5%) toxinotype
      XI/PCR ribotype 033 or 033-like strain. The description of such strains raises
      the question of the role of binary toxin as a virulence factor and could have
      implications for laboratory diagnostics that currently rarely include testing for
      binary toxin. 

PMID- 25755888
TI  - Candidatus 'Rickettsia senegalensis' in cat fleas in Senegal.
AB  - Epidemiological studies of Rickettsia felis and related bacteria are very
      important, because the natural cycle of this important infection has not yet been
      established. The recent emergence of R. felis-associated febrile diseases in West
      and East Africa demands insightful epidemiological studies of the vectors and
      reservoirs of this bacterium in Africa. Twenty-nine cat fleas, Ctenocephalides
      felis, were tested for the presence of rickettsiae, including R. felis,
      bartonellae, and borreliae, with specific quantitative real-time PCR assays.
      Supporting our previous studies, R. felis was not detected in the fleas
      collected. In addition, neither Bartonella nor Borrelia was found. In five (17%)
      examined fleas, we found another species of rickettsia. We isolated three
      rickettsial strains, and genetic analysis demonstrated that these strains
      represent a probable new species, provisionally called Candidatus Rickettsia
      senegalensis here. 

PMID- 25755887
TI  - Fatal Chromobacterium violaceum bacteraemia in rural Bandundu, Democratic
      Republic of the Congo.
AB  - We describe the first case of bacteraemia caused by Chromobacterium violaceum in
      the Democratic Republic of the Congo. This diagnosis was made in an apparently
      healthy adult who was admitted to a rural hospital of the province of Bandundu
      with severe community-acquired sepsis. The patient developed multi-organ failure
      and died; to our knowledge, this is the first reported fatal case in an adult in
      Africa. 

PMID- 25755889
TI  - Epidemiologic characteristics associated with ST23 clones compared to ST1 and
      ST47 clones of Legionnaires disease cases in France.
AB  - In France, approximately 1200 cases of Legionnaires disease (LD) are reported
      annually, and isolates are available for approximately 20% of cases identified
      since 2000. All Legionella pneumophila serogroup 1 (sg1) isolates are
      characterized by sequence-based typing at the National Reference Centre. LD cases
      caused by L. pneumophila sg1 reported from 2008 through 2012 were considered for
      the study. Our study objective was to describe cases according to their sequence
      type (ST). We also constructed multivariable modified Poisson regression models
      to estimate the incidence rate ratio (IRR) and to identify characteristics
      potentially associated with ST23 clones compared to ST1 and ST47 clones. We
      studied 1192 patients infected by ST1 (n = 109), ST23 (n = 236), ST47 (n = 123)
      or other STs (n = 724). The geographic distribution of the ST23 cases across the
      country was significantly different compared to other ST groups. This genotype
      was significantly associated with the absence of corticosteroid therapy compared
      to ST1 (IRR = 0.56; p 0.016). Concerning exposure, the ST23 genotype was
      significantly less associated with hospital-acquired infections compared to ST1
      (IRR = 0.32; p 0.001), but it was more associated with infections acquired in
      hospitals and elderly settings compared with ST47. Finally, the ST23 genotype was
      less frequently associated with travel than other STs. Despite the large number
      of cases of ST23 infection, we did not identify any characteristics specific to
      this ST. However, we identified independent associations between ST1 and
      nosocomial transmission and steroid therapy. These findings should encourage
      further exploration, especially in terms of environmental diffusion, strain
      virulence and host factors. 

PMID- 25755890
TI  - Emergence of KPC-producing Klebsiella pneumoniae ST512 isolated from
      cerebrospinal fluid of a child in Algeria.
AB  - We report class A carbapenemase (KPC)-3-producing Klebsiella pneumoniae
      meningitis in a 6-month-old child in Algeria. Multilocus sequence typing showed
      that the sequence type obtained corresponded to ST512, an allelic single-locus
      variant of the pandemic ST258 widely distributed in KPC producers from Europe. To
      our knowledge, this is the first report of KPC-3-producing K. pneumoniae ST512 in
      a North African country. 

PMID- 25755891
TI  - Identification of immunodominant proteins of the microalgae Prototheca by
      proteomic analysis.
AB  - Prototheca zopfii associated with bovine mastitis and human protothecosis exists
      as two genotypes, of which genotype 1 is considered as non-infectious and
      genotype 2 as infectious. The mechanism of infection has not yet been described.
      The present study was aimed to identify genotype 2-specific immunodominant
      proteins. Prototheca proteins were separated using two-dimensional gel
      electrophoresis. Subsequent western blotting with rabbit hyperimmune serum
      revealed 28 protein spots. Matrix-assisted laser desorption ionization time-of
      flight mass spectrometry analysis resulted in the identification of 15 proteins
      including malate dehydrogenase, elongation factor 1-alpha, heat shock protein 70,
      and 14-3-3 protein, which were previously described as immunogenic proteins of
      other eukaryotic pathogens. 

PMID- 25755892
TI  - Roles of bovine Waddlia chondrophila and Chlamydia trachomatis in human preterm
      birth.
AB  - Waddlia chondrophila and Chlamydia trachomatis are intracellular bacteria
      associated with human miscarriage. We investigated their role in human preterm
      birth. Whereas presence of Chlamydia trachomatis DNA in genital tract was
      associated with human preterm birth, Waddlia was not, despite being present in
      women's genital tracts. 

PMID- 25755893
TI  - Cryptococcus neoformans meningitis with negative cryptococcal antigen: Evaluation
      of a new immunochromatographic detection assay.
AB  - Detection of cryptococcal antigen in serum or cerebrospinal fluid allows
      cryptococcal meningitis diagnosis within few hours with >90% sensitivity. In an
      HIV-positive patient with Cryptococcus neoformans meningitis, initial antigen
      detection by immunoagglutination was negative. We thus evaluated a new
      immunochromatographic detection assay that exhibited a higher sensitivity. 

PMID- 25755895
TI  - Second-degree interatrial block in hemodialysis patients.
AB  - Interatrial conduction delays manifest as a prolonged P-wave duration on surface
      ECG and the term interatrial block (IAB) has been coined. They are usually fixed,
      but cases of intermittent IAB have been described, suggesting functional
      conduction block at the Bachmann bundle region. We report 2 cases of patients on
      chronic hemodialysis therapy presenting with intermittent IAB. 

PMID- 25755894
TI  - Ponseti casting for severe club foot deformity: are clinical outcomes promising?
AB  - Between 2007 and 2010, a prospective study was done on 85 patients with severe
      idiopathic nonsyndromic clubfeet, in our center. Demographic features, severity
      of the deformity before and after serial casting according to Dimeglio
      classification, and complications were assessed. The mean age of the patients was
      8 days and 69% were male. The mean follow-up period was 26 months. The average
      number of castings used to correct the deformity was 5.7 times (range: 4 to 8).
      Tenotomy was performed in 76 (89.4%) of the feet. In all patients, plantigrade
      foot was achieved. Tenotomy occurred more in patients with higher Dimeglio
      scores. Although patients who underwent Achilles tenotomy began to walk later
      than those who did not (13 +/- 7.2 versus 9.2 +/- 18), it was not significant (P
      = 0.06). Relapse rate, at the end of follow-up, was 27.1%. Dimeglio score before
      casting was 16 +/- 3.4 and at the end of follow-up it was 1.6 +/- 6.2. The
      patients with bilateral clubfeet had inferior final outcome compared to those
      with unilateral clubfoot. Eighty percent of parents' were completely satisfied
      with their child's gait and foot appearance (94.1%). Ponseti method of
      manipulation and casting is a valuable technique in severe club foot as well as
      in common types. 

PMID- 25755896
TI  - A Whole-Food Plant-Based Diet Reversed Angina without Medications or Procedures.
AB  - A 60-year-old man presented with typical angina and had a positive stress test.
      He declined both drug therapy and invasive testing. Instead, he chose to adopt a
      whole-food plant-based diet, which consisted primarily of vegetables, fruits,
      whole grains, potatoes, beans, legumes, and nuts. His symptoms improved rapidly,
      as well as his weight, blood pressure, and cholesterol levels. Plant-based diets
      have been associated with improved plasma lipids, diabetes control, coronary
      artery disease and with a reduction in mortality. Adoption of this form of
      lifestyle therapy should be among the first recommendations for patients with
      atherosclerosis. 

PMID- 25755897
TI  - Acute headache at emergency department: reversible cerebral vasoconstriction
      syndrome complicated by subarachnoid haemorrhage and cerebral infarction.
AB  - Introduction. Reversible cerebral vasoconstriction syndrome is becoming widely
      accepted as a rare cause of both ischemic and haemorrhagic stroke and should be
      evocated in case of thunderclap headaches associated with stroke. We present the
      case of a patient with ischemic stroke associated with cortical subarachnoid
      haemorrhage (cSAH) and reversible diffuse arteries narrowing, leading to the
      diagnosis of reversible vasoconstriction syndrome. Case Report. A 48-year-old
      woman came to the emergency department because of an unusual thunderclap
      headache. The computed tomography of the brain completed by CT-angiography was
      unremarkable. Eleven days later, she was readmitted because of a left
      hemianopsia. One day after her admission, she developed a sudden left
      hemiparesis. The brain MRI showed ischemic lesions in the right frontal and
      occipital lobe and diffuse cSAH. The angiography showed vasoconstriction of the
      right anterior cerebral artery and stenosis of both middle cerebral arteries.
      Nimodipine treatment was initiated and vasoconstriction completely regressed on
      day 16 after the first headache. Conclusion. Our case shows a severe reversible
      cerebral vasoconstriction syndrome where both haemorrhagic and ischemic
      complications were present at the same time. The history we reported shows that
      reversible cerebral vasoconstriction syndrome is still underrecognized, in
      particular in general emergency departments. 

PMID- 25755898
TI  - Epstein-barr virus-related hemophagocytic lymphohistiocytosis: hematologic
      emergency in the critical care setting.
AB  - Hemophagocytic lymphohistiocytosis (HLH) is a rare and potential life-threatening
      clinical syndrome that results from uncontrolled activation of the immune system.
      Secondary HLH, more commonly observed in adult patients, is seen in the context
      of underlying triggering conditions. Epstein-Barr virus (EBV) has been recognized
      as the leading infectious cause and is associated with a poor outcome. As
      clinical and laboratory features of HLH could overlap with septic shock syndrome
      in most patients, the diagnosis of HLH, especially in adults, is the most
      challenging aspect of the disease that results in delayed recognition and
      treatment of rapidly progressive multiorgan system failure. We report a case of
      Hemophagocytic lymphohistiocytosis in a patient who presented with signs of
      septic shock syndrome and we review the literature on the topic. 

PMID- 25755899
TI  - Serum total tryptase level confirms itself as a more reliable marker of mast
      cells burden in mast cell leukaemia (aleukaemic variant).
AB  - Mast cell leukemia (MCL) is a very rare form of systemic mastocytosis (SM) with a
      short median survival of 6 months. We describe a case of a 65-year-old woman with
      aleukaemic variant of MCL with a very high serum total tryptase level of 2255
      MUg/L at diagnosis, which occurred following an episode of hypotensive shock. She
      fulfilled the diagnostic criteria of SM, with a bone marrow smear infiltration of
      50-60% of atypical mast cells (MCs). She tested negative for the KIT D816V
      mutation, without any sign of organ damage (no B- or C-findings) and only few
      mediator-related symptoms. She was treated with antihistamine alone and then with
      imatinib for the appearance of anemia. She maintained stable tryptase level and a
      very indolent clinical course for twenty-two months; then, she suddenly
      progressed to acute MCL with a serum tryptase level up to 12960 MUg/L. The
      patient died due to haemorrhagic diathesis twenty-four months after diagnosis.
      This clinical case maybe represents an example of the chronic form of mast cell
      leukemia, described as unpredictable disease, in which the serum total tryptase
      level has confirmed itself as a reliable marker of mast cells burden regardless
      of the presence of other signs or symptoms. 

PMID- 25755900
TI  - Lower leg compartment syndrome after appendicectomy.
AB  - A 10-year-old boy presented with severe left lower leg pain, uncontrolled with
      increasing analgesia after appendicectomy. A diagnosis of acute compartment
      syndrome was made after a delayed referral to the orthopaedic service. The
      patient subsequently underwent an emergency fasciotomy and made a good functional
      recovery. To the best of our knowledge this is the first reported case of
      paediatric lower leg compartment syndrome after appendicectomy in the literature.
      The case report serves to highlight the importance of maintaining a high index of
      suspicion for compartment syndrome. 

PMID- 25755901
TI  - Recurrent laryngeal edema imitating angioedema caused by dislocated screw after
      anterior spine surgery.
AB  - The anterior cervical spine surgery is a common procedure to stabilize vertebrae
      damaged by various diseases. The plates and screws are usually used in the spine
      fixation. This kind of instrumentation may detach from the bones which is a rare
      but well-known complication. A 77-year-old male presented to the
      otorhinolaryngology department with throat pain, choking, and dysphagia. At first
      the angioedema was diagnosed and he was treated conservatively. The endoscopy
      revealed laryngeal edema, being more defined on the right side with right vocal
      fold paresis. CT scans showed the stabilizing plate with two screws attached
      tightly and the back-out of the third screw toward soft tissue of the neck. In
      the meantime, his condition deteriorated and he needed tracheotomy. In few days
      the surgical removal of the dislocated screw was performed successfully. Although
      two-month follow-up reported no obstruction of the larynx, the vocal folds
      paresis with gradual functional improvement was observed. Long-term complication
      of anterior spine surgery sometimes may suggest laryngeal angioedema at first. If
      the conservative treatment is ineffective and there is a history of anterior
      spine surgery, the clinicians should consider the displacement of the plate or
      screws in differential diagnosis. 

PMID- 25755902
TI  - Isolated kaposi sarcoma of the tonsil: a case report and review of the scientific
      literature.
AB  - Kaposi sarcoma is a tumour caused by human herpes virus 8, also known as Kaposi
      sarcoma-associated herpes virus. It usually affects the skin and oral mucosa;
      however, it can also sometimes affect the lungs, the liver, the stomach, the
      bowel, and lymph nodes. Several body sites may be affected simultaneously. The
      involvement of the tonsils is rare. We described an isolated localization of
      Kaposi's sarcoma of the right tonsil in a HIV-positive patient. 

PMID- 25755903
TI  - Congenital oligodendroglioma: clinicopathologic and molecular assessment with
      review of the literature.
AB  - Oligodendroglioma is an infiltrating glial neoplasm frequently seen in adults.
      Pediatric oligodendrogliomas are rare, with very few cases presenting in infancy
      and only rare congenital examples. In contrast to adult oligodendrogliomas,
      pediatric cases typically lack 1p/19q codeletion. Herein we report a case of WHO
      grade II oligodendroglioma diagnosed in a 7-month-old male infant. The patient
      initially presented at 3 months of age with symptoms suspicious for seizure.
      Initial workup including electroencephalography (EEG), electrocardiogram (EKG),
      and computed tomography (CT) of the head was negative. His symptoms persisted,
      and subsequent magnetic resonance imaging (MRI) performed at age of 7 months
      revealed a 2 cm contrast-enhancing left temporal lobe mass. The mass was excised
      and the microscopic appearance was that of a classic low grade oligodendroglioma
      composed of cells with uniformly round nuclei, perinuclear halos, delicate
      branching capillaries, and an absence of high grade features. Mutant specific
      (R132H) isocitrate dehydrogenase-1 (IDH1) immunohistochemistry was negative, and
      the tumor lacked detectable 1p or 19q deletions by fluorescent in situ
      hybridization (FISH). The onset of neurological symptoms in early infancy
      followed by the positive MRI findings suggests that this case represents a rare
      example of congenital oligodendroglioma. 

PMID- 25755904
TI  - Lymphocutaneous Sporotrichosis during Treatment with Anti-TNF-Alpha Monotherapy.
AB  - Sporotrichosis is an infectious disease caused by Sporothrix schenckii, a
      dimorphic fungus isolated for the first time in 1896 by Benjamin Schenck from a
      36-year-old male patient presenting lesions on the right hand and arm. The
      infection generally occurs by traumatic inoculation of soil, plants, and organic
      matter contaminated with the fungus. Different clinical syndromes are described
      as a direct consequence of S. schenckii infection, including lymphocutaneous and
      disseminated forms, although extracutaneous presentations are reported most
      frequently in AIDS patients. Here we describe the case of a 57-year-old Caucasian
      male diagnosed in 2004 with ankylosing spondylitis under stable treatment with
      adalimumab monotherapy (40 mg every other week). During a routine follow-up visit
      in March 2013, he presented with multiple nodular lesions arranged in a linear
      fashion along the left hand and forearm. After diagnostic aspiration of the
      lesions, lymphocutaneous sporotrichosis was diagnosed and appropriate therapy
      started. 

PMID- 25755905
TI  - Towards an off-the-shelf vaccine therapy targeting shared B-cell tumor idiotypes.
AB  - The ideal tumor antigen is one expressed selectively by the tumor, present in all
      cancer patients, essential for tumor survival and nonetheless able to induce both
      humoral and cellular immune response. The personalized idiotype (Id) of the
      surface immunoglobulin is a tumor specific antigen in that it is expressed on
      clonal B-cell tumors, mediates B-cell survival, and induces tumor specific
      immunity in both human and animal models. With the availability of monoclonal
      antibodies against B cells, such as rituximab, the cellular immune response
      mediated by specific T cells has gained more importance as a combination therapy
      for the complete elimination of residual tumor cells in lymphoma and myeloma. 

PMID- 25755907
TI  - Dkk-1 and IL-7 in plasma of patients with multiple myeloma prevent
      differentiation of mesenchymal stem cells into osteoblasts.
AB  - Bone disease is the leading cause of morbidity associated with multiple myeloma
      (MM). Lytic bone lesions have been detected in 90% of patients diagnosed with MM
      and present a great therapeutic challenge. After the removal of the tumor burden,
      the bone lesions persist and the bone remodeling homeostasis is not restored even
      in patients in clinical remission. To determine whether systemic factors
      generated by malignant MM cells can skew the osteoblast (OB) differentiation
      program of normal mesenchymal stem cells (MSCs), we generated an immortalized
      bone marrow MSC line (hTERT-MSC). The hTERT-MSCs were exposed to plasma from
      healthy donors and patients with MM. Cells grown in media supplemented with
      plasma from MM patients failed to differentiate into OBs, while the hTERT-MSCs
      grown in the presence of normal human plasma generated OB clusters that
      mineralized calcium, expressed Runx2, and were positive for alkaline phosphatase,
      fibronectin, collagen I, osteocalcin, and osteopontin. Blocking Dickkopf-1 (Dkk
      1) and interleukin-7 (IL-7) in MM plasma restored proper OB differentiation of
      hTERT-MSCs. Finally, we show that hTERT-MSCs cultured in the presence of MM
      plasma adopt a cancer-associated stroma phenotype. Thus, we show, that systemic
      factors present in the plasma of patients with MM affect the behavior of non
      malignant MSCs and contribute to the sustained bone disease reported in MM. 

PMID- 25755906
TI  - The role of glucocorticoid receptor (GR) polymorphisms in human erythropoiesis.
AB  - Glucocorticoids are endogenous steroid hormones that regulate several biological
      functions including proliferation, differentiation and apoptosis in numerous cell
      types in response to stress. Synthetic glucocorticoids, such as dexamethasone
      (Dex) are used to treat a variety of diseases ranging from allergy to depression.
      Glucocorticoids exert their effects by passively entering into cells and binding
      to a specific Glucocorticoid Receptor (GR) present in the cytoplasm. Once
      activated by its ligand, GR may elicit cytoplasmic (mainly suppression of p53),
      and nuclear (regulation of transcription of GR responsive genes), responses.
      Human GR is highly polymorphic and may encode > 260 different isoforms. This
      polymorphism is emerging as the leading cause for the variability of phenotype
      and response to glucocorticoid therapy observed in human populations. Studies in
      mice and clinical observations indicate that GR controls also the response to
      erythroid stress. This knowledge has been exploited in-vivo by using synthetic GR
      agonists for treatment of the erythropoietin-refractory congenic Diamond Blackfan
      Anemia and in-vitro to develop culture conditions that may theoretically generate
      red cells in numbers sufficient for transfusion. However, the effect exerted by
      GR polymorphism on the variability of the phenotype of genetic and acquired
      erythroid disorders observed in the human population is still poorly appreciated.
      This review will summarize current knowledge on the biological activity of GR and
      of its polymorphism in non-hematopoietic diseases and discuss the implications of
      these observations for erythropoiesis. 

PMID- 25755908
TI  - Comparative of three methods (ELIZA, MAIPA and flow cytometry) to determine anti
      platelet antibody in children with ITP.
AB  - Immune (idiopathic) thrombocytopenic purpurea (ITP) is an autoimmune disease
      characterized by the increased anti-platelet antibodies in the patient's sera and
      decreased platelets in the blood circulation. This study has determined and
      characterized the antiplatelet glycoproteins in children with ITP. Thirty eight
      children, who were hospitalized with clinical signs of ITP in Mofid Children
      Hospital (Tehran, Iran) during 18 months, went under our clinical studies in a
      research project. ELISA, Flow cytometry and MAIPA (Monoclonal Antibody
      Immobilization of Platelet Antigens) methods were employed to determine serum
      anti-platelet antibodies level. The anti-platelet antibodies level above mean +
      3SD of control group was assumed as positive. The platelet counts ranged between
      2 * 10(9)/L and 100 * 10(9)/L. Among the patients 63.5% of them were anti
      platelet antibodies positive with ELISA method. Results of platelet lysate method
      showed that 51.7% of patients had antibodies against platelet antigens. Antibody
      against platelet GPIIb/IIIa, GPIb/IX and GPIa/IIa using MAIPA method were 48%,
      54% and 25% respectively. In flow cytometry 62% of patients showed anti-platelet
      antibodies. The comparison of three methods shows that since MAIPA is the
      specific method for the detection of very small amount of antibody against
      glycoprotein antigens, it has the advantage of differentiating between immune and
      non-immune thrombocytopenia. 

PMID- 25755909
TI  - Long-lasting complete response to imatinib in a patient with systemic
      mastocytosis exhibiting wild type KIT.
AB  - Systemic mastocytosis (SM) is a hematopoietic disorder characterized by abnormal
      expansion of mast cells (MCs) in visceral organs. The skin is involved in most
      cases. In adult patients the transforming KIT mutation D816V is usually present
      and confers resistance against imatinib. Therefore, imatinib is not recommended
      for patients with KIT D816V+ SM. Nonetheless, imatinib may work in patients with
      SM lacking KIT D816V. However, little is known about long-term efficacy and
      safety of this drug in SM. We report on a 62-year-old female patient with
      indolent SM (ISM) who suffered from severe debilitating skin involvement despite
      therapy with anti-mediator-type drugs, psoralen and ultraviolet-A-radiation.
      Although multifocal MC infiltrates were detected in the bone marrow by
      immunohistochemistry, no KIT mutation was found by sequencing analysis. In 2003,
      treatment with imatinib (induction, 400 mg/day; maintenance, 200 mg/day) was
      initiated. During therapy, skin lesions and tryptase levels decreased. Treatment
      was well tolerated without any side effects. After 10 years, skin lesions have
      disappeared and the tryptase level is within normal range. This case-study
      confirms the long-term efficacy and safety of imatinib in patients with SM
      lacking activating KIT mutations. Imatinib should be considered in select cases
      of SM in whom MCs exhibit wild-type KIT. 

PMID- 25755910
TI  - Imported visceral leishmaniasis - unexpected bone marrow diagnosis in a patient
      with fever, pancytopenia, and splenomegaly.
AB  - Leishmaniasis is spreading from mediterranean countries to the north of Europe.
      The Alps are not an endemic region and there are only few reports of sporadic
      cases. We report the case of a 72 year old male who presented after a syncope
      with fever, cough and a sacral skin rash. Clinical examination revealed
      splenomegaly, elevated liver enzymes and pancytopenia; differential diagnosis
      included myeloproliferative or lymphoproliferative disorders, infections and auto
      immune conditions that cause enlargement of the spleen and liver diseases,
      however, all tests were negative. In (18)FDG PET computerized tomography,
      pathological and diffuse uptake in the spleen was seen, with mild and homogeneous
      FDG uptake in the bone marrow and normal tracer uptake elsewhere in the body.
      Bone marrow aspiration revealed the presence of numerous intra- and extracellular
      Leishmania amastigotes. Travel history indicated that he had been in Sardinia for
      a 7-day vacation several months ago. The patient promptly responded to treatment
      with liposomal amphotericin B. Imported visceral leishmaniasis is likely to be
      seen more frequently in non-endemic regions and fever, pancytopenia and
      splenomegaly are diagnostic clues, whereas diagnostic confirmation may be done by
      detection of Leishmania spp. amastigotes in the bone marrow. 

PMID- 25755911
TI  - Concomitant use of radiotherapy and two topoisomerase inhibitors to treat adult T
      cell leukemia with a radiotherapy-resistant bulky disease: a case series.
AB  - Concomitant chemoradiotherapy is established as the standard treatment to improve
      the prognosis of several types of solid tumor, but has not been the general
      practice for hematological malignancies. Here, I report two cases of adult T-cell
      leukemia (ATL) with a radiotherapy-resistant bulky disease treated with
      concomitant radiotherapy and two topoisomerase inhibitors: etoposide (VP-16) and
      irinotecan (CPT-11). Patient 1 was a 78-year-old man with chemotherapy-resistant
      inguinal bulky mass. Radiotherapy (total 40 Gy) for this inguinal lesion was
      started; however, the bulky disease was found to be resistant to radiotherapy and
      progressed. VP-16 and CPT-11 were administered in addition to radiotherapy (after
      a total of 20 Gy of radiotherapy). Patient 2 was a 71-year-old man with a
      solitary bulky mass in left cervical lesion. Various previous chemotherapy and
      radiotherapy approaches had not been able to control the disease. Six months
      after first radiotherapy, the bulky disease rapidly progressed with the
      occurrence of pain. Second radiotherapy (30 Gy) was started with simultaneous
      administration of CPT-11 and VP-16. In both cases, the bulky disease gradually
      regressed and completely disappeared by the end of radiotherapy. Thus, flexible
      adaptation of concomitant chemoradiotherapy including two topoisomerase
      inhibitors may offer a potential therapeutic option for radiotherapy-resistant
      bulky diseases, even in hematological malignancies. 

PMID- 25755912
TI  - Hawai'i's nursing workforce: keeping pace with healthcare.
AB  - Nursing is the largest segment of the healthcare workforce, but over the next
      decade even more nurses will be required. Changing population demographics, new
      technologies, and evolving models of healthcare will stimulate expansion of
      nursing roles and the need for a highly educated nursing workforce. The current
      nursing workforce is aging, and large numbers of retirements are anticipated. By
      2025, the United States is expected to experience a nursing shortage; in Hawai'i
      this shortfall is forecast to be 3,311 professional nurses. Currently there are
      nine nursing programs across the state in public and private universities and
      colleges. These programs are partnering to implement the Institute of Medicine's
      recommendations for the future of nursing. In Hawai'i, nursing practice is being
      expanded; different pathways to advanced nursing education are being implemented;
      and nurses are partnering with other groups to reshape healthcare. The Hawai'i
      State Center for Nursing collects ongoing data on the nursing workforce to inform
      strategic planning. Current gaps in nursing specialty education include school
      health and mental health. The purpose of this paper is to provide an overview of
      Hawai'i's nursing workforce in relationship to statewide population demographics,
      healthcare needs and gaps, and then outline steps being taken by the profession
      to address these needs and gaps while implementing the Institute of Medicine
      recommendations. 

PMID- 25755913
TI  - Recurrent papillary thyroid carcinoma with pleural metastasis diagnosed by
      effusion cytology: a report of cases with clinicopathologic correlation.
AB  - Papillary thyroid carcinoma (PTC) is typically an indolent disease characterized
      by slow growth and a favorable prognosis. In rare instances, this disease may
      metastasize to the pleura and manifest as a malignant pleural effusion. We report
      3 female patients of Japanese/Okinawan ancestry with a history of PTC who
      presented with hydrothorax. Cytologic examination in conjunction with
      immunohistochemical staining enabled a definitive diagnosis of metastatic PTC.
      Molecular analysis of the mitogen activated protein kinase (MAPK) and
      phosphatidylinositol 3-kinase (PI3K) pathways demonstrated the presence of the v
      raf murine sarcoma viral oncogene homolog B (BRAF)(V600E) mutation in 2 of our 3
      patients, with the absence of any other clinically significant mutations in all
      cases. Further investigation is necessary to elucidate the molecular and
      environmental mechanisms involved in this aggressive manifestation of PTC. 

PMID- 25755914
TI  - Impact of utilizing pharmacy students as workforce for Hawai'i Asthma Friendly
      Pharmacy Project.
AB  - A partnership was formed between the University of Hawai'i at Hilo Daniel K.
      Inouye College of Pharmacy (DKICP) and the Department of Health to carry out the
      Hawai'i Asthma Friendly Pharmacy Project (HAFPP), which utilizes pharmacy
      students as a workforce to administer Asthma Control TestsTM (ACT), and provide
      Asthma Action Plans (AAP) and inhaler technique education. Evaluation of data
      from a pilot project in 2008 with first and second year students prompted more
      intensive training in therapeutics, inhaler medication training, and
      communication techniques. Data collection began when two classes of students were
      first and second year students and continued until the students became fourth
      year students in their advanced experiential ambulatory care clinic and retail
      community pharmacy rotations. Patients seen included pediatric (32%) and adult
      (68%) aged individuals. Hawai'i County was the most common geographic site (50%)
      and most sites were retail pharmacies (72%). Administered ACT surveys (N=96)
      yielded a mean score of 19.64 (SD +/-3.89). In addition, 12% of patients had
      received previous ACT, and 47% had previous AAPs. Approximately 83% of patients
      received an additional intervention of AAP and inhaler education with 73% of
      these patients able to demonstrate back proper inhaler technique. Project
      challenges included timing of student training, revising curriculum and logistics
      of scheduling students to ensure consistent access to patients. 

PMID- 25755915
TI  - Medical school hotline: The University of Hawai'i John A. Burns School of
      Medicine Department of Psychiatry: past, present, and future.

PMID- 25755916
TI  - Insights in public health: Electronic cigarettes: marketing to Hawai'i's
      adolescents.
AB  - Electronic cigarettes (e-cigarettes) are an emerging phenomenon that is becoming
      increasingly popular among adolescents. Current e-cigarette use among adolescents
      has more than doubled in the past few years nationally and more than tripled in
      Hawai'i, despite the fact that safety in terms of health and injury from use is
      widely unknown. The use of e-cigarettes among adolescents is of particular
      concern because they may act as a gateway to smoking conventional tobacco
      cigarettes, substitute for cigarettes where smoking would normally not be
      allowed, and weaken the effect of clean air policies, and displace effective
      smoking cessation treatments. Additionally, the use of e-cigarettes may lead to
      the use of conventional cigarettes. There is special concern that e-cigarette
      companies are recruiting adolescents who would not have otherwise tried smoking
      by using tactics such as offering e-cigarettes in attractive flavorings and using
      the same successful strategies to market their product as tobacco companies have
      used for conventional cigarettes in past decades. It has been shown that exposure
      to cigarette marketing is related to initiation and progression in adolescent
      smoking. Yet, there remains no regulation on the marketing of e-cigarettes to
      adolescents. It can be extrapolated that expanded regulation that includes limits
      on the marketing of e-cigarettes may help decrease use among adolescents and
      prevent the possible increase of smoking rates. 

PMID- 25755919
TI  - Maintenance energy requirements of odor detection, explosive detection and human
      detection working dogs.
AB  - Despite their important role in security, little is known about the energy
      requirements of working dogs such as odor, explosive and human detection dogs.
      Previous researchers have evaluated the energy requirements of individual canine
      breeds as well as dogs in exercise roles such as sprint racing. This study is the
      first to evaluate the energy requirements of working dogs trained in odor,
      explosive and human detection. This retrospective study evaluated twenty adult
      dogs who maintained consistent body weights over a six month period. During this
      time, the average energy consumption was [Formula: see text] or two times the
      calculated resting energy requirement ([Formula: see text]). No statistical
      differences were found between breeds, age or sex, but a statistically
      significant association (p = 0.0033, R-square = 0.0854) was seen between the
      number of searches a dog performs and their energy requirement. Based on this
      study's population, it appears that working dogs have maintenance energy
      requirements similar to the 1974 National Research Council's (NRC) maintenance
      energy requirement of [Formula: see text] (National Research Council (NRC), 1974)
      and the [Formula: see text] reported for young laboratory beagles (Rainbird &
      Kienzle, 1990). Additional research is needed to determine if these data can be
      applied to all odor, explosive and human detection dogs and to determine if other
      types of working dogs (tracking, search and rescue etc.) have similar energy
      requirements. 

PMID- 25755920
TI  - Morphology of the jaw, suspensorial, and opercle musculature of Beloniformes and
      related species (Teleostei: Acanthopterygii), with a special reference to the m.
      adductor mandibulae complex.
AB  - The taxon Beloniformes represents a heterogeneous group of teleost fishes that
      show an extraordinary diversity of jaw morphology. I present new anatomical
      descriptions of the jaw musculature in six selected beloniforms and four closely
      related species. A reduction of the external jaw adductor (A1) and a changed
      morphology of the intramandibular musculature were found in many Beloniformes.
      This might be correlated with the progressively reduced mobility of the upper and
      lower jaw bones. The needlefishes and sauries, which are characterised by
      extremely elongated and stiffened jaws, show several derived characters, which in
      combination enable the capture of fish at high velocity. The ricefishes are
      characterised by several derived and many plesiomorphic characters that make
      broad scale comparisons difficult. Soft tissue characters are highly diverse
      among hemiramphids and flying fishes reflecting the uncertainty about their
      phylogenetic position and interrelationship. The morphological findings presented
      herein may help to interpret future phylogenetic analyses using cranial
      musculature in Beloniformes. 

PMID- 25755921
TI  - Perennial growth of hermatypic corals at Rottnest Island, Western Australia (32
      degrees S).
AB  - To assess the viability of high latitude environments as coral refugia, we report
      measurements of seasonal changes in seawater parameters (temperature, light, and
      carbonate chemistry) together with calcification rates for two coral species,
      Acropora yongei and Pocillopora damicornis from the southernmost geographical
      limit of these species at Salmon Bay, Rottnest Island (32 degrees S) in Western
      Australia. Changes in buoyant weight were normalised to colony surface areas as
      determined from both X-ray computed tomography and geometric estimation.
      Extension rates for A. yongei averaged 51 +/- 4 mm y(-1) and were comparable to
      rates reported for Acroporid coral at other tropical and high latitude locations.
      Mean rates of calcification for both A. yongei and P. damicornis in winter were
      comparable to both the preceding and following summers despite a mean seasonal
      temperature range of ~6  degrees C (18.2 degrees -24.3  degrees C) and more than
      two-fold changes in the intensity of downwelling light. Seasonal calcification
      rates for A. yongei (1.31-2.02 mg CaCO3 cm(-2) d(-1)) and P. damicornis (0.34
      0.90 mg CaCO3 cm(-2) d(-1)) at Salmon Bay, Rottnest Island were comparable to
      rates from similar taxa in more tropical environments; however, they appeared to
      decline sharply once summer temperatures exceeded 23  degrees C. A coral
      bleaching event observed in December 2013 provided further evidence of how coral
      at Rottnest Island are still vulnerable to the deleterious effects of episodic
      warming despite its high latitude location. Thus, while corals at Rottnest Island
      can sustain robust year-round rates of coral growth, even over cool winter
      temperatures of 18 degrees -19  degrees C, there may be limits on the extent that
      such environments can provide refuge against the longer term impacts of
      anthropogenic climate change. 

PMID- 25755918
TI  - Obsessive-compulsive disorder is associated with broad impairments in executive
      function: A meta-analysis.
AB  - Obsessive-compulsive disorder (OCD) is a serious and often chronically disabling
      condition. The current dominant model of OCD focuses on abnormalities in
      prefrontal-striatal circuits that support executive function (EF). While there is
      growing evidence for EF impairments associated with OCD, results have been
      inconsistent, making the nature and magnitude of these impairments controversial.
      The current meta-analysis uses random-effects models to synthesize 110 previous
      studies that compared participants with OCD to healthy control participants on at
      least one neuropsychological measure of EF. The results indicate that individuals
      with OCD are impaired on tasks measuring most aspects of EF, consistent with
      broad impairment in EF. EF deficits were not explained by general motor slowness
      or depression. Effect sizes were largely stable across variation in demographic
      and clinical characteristics of samples, although medication use, age, and gender
      moderated some effects.

PMID- 25755923
TI  - Quantification of Pseudomonas aeruginosa in multispecies biofilms using PMA-qPCR.
AB  - Multispecies biofilms are an important healthcare problem and may lead to
      persistent infections. These infections are difficult to treat, as cells in a
      biofilm are highly resistant to antimicrobial agents. While increasingly being
      recognized as important, the properties of multispecies biofilms remain poorly
      studied. In order to do so, the quantification of the individual species is
      needed. The current cultivation-based approaches can lead to an underestimation
      of the actual cell number and are time-consuming. In the present study we set up
      a culture-independent approach based on propidium monoazide qPCR (PMA-qPCR) to
      quantify Pseudomonas aeruginosa in a multispecies biofilm. As a proof of concept,
      we explored the influence of the combined presence of Staphylococcus aureus,
      Streptococcus anginosus and Burkholderia cenocepacia on the antimicrobial
      susceptibility of P. aeruginosa using this PMA-qPCR approach. 

PMID- 25755922
TI  - Nucleotide variation and balancing selection at the Ckma gene in Atlantic cod:
      analysis with multiple merger coalescent models.
AB  - High-fecundity organisms, such as Atlantic cod, can withstand substantial natural
      selection and the entailing genetic load of replacing alleles at a number of loci
      due to their excess reproductive capacity. High-fecundity organisms may reproduce
      by sweepstakes leading to highly skewed heavy-tailed offspring distribution.
      Under such reproduction the Kingman coalescent of binary mergers breaks down and
      models of multiple merger coalescent are more appropriate. Here we study
      nucleotide variation at the Ckma (Creatine Kinase Muscle type A) gene in Atlantic
      cod. The gene shows extreme differentiation between the North (Canada, Greenland,
      Iceland, Norway, Barents Sea) and the South (Faroe Islands, North-, Baltic-,
      Celtic-, and Irish Seas) with FST > 0.8 between regions whereas neutral loci show
      no differentiation. This is evidence of natural selection. The protein sequence
      is conserved by purifying selection whereas silent and non-coding sites show
      extreme differentiation. The unfolded site-frequency spectrum has three modes, a
      mode at singleton sites and two high frequency modes at opposite frequencies
      representing divergent branches of the gene genealogy that is evidence for
      balancing selection. Analysis with multiple-merger coalescent models can account
      for the high frequency of singleton sites and indicate reproductive sweepstakes.
      Coalescent time scales vary with population size and with the inverse of variance
      in offspring number. Parameter estimates using multiple-merger coalescent models
      show that times scales are faster than under the Kingman coalescent. 

PMID- 25755924
TI  - Loss of CITED1, an MITF regulator, drives a phenotype switch in vitro and can
      predict clinical outcome in primary melanoma tumours.
AB  - CITED1 is a non-DNA binding transcriptional co-regulator whose expression can
      distinguish the 'proliferative' from 'invasive' signature in the phenotype
      switching model of melanoma. We have found that, in addition to other
      'proliferative' signature genes, CITED1 expression is repressed by TGFbeta while
      the 'invasive' signature genes are upregulated. In agreement, CITED1 positively
      correlates with MITF expression and can discriminate the MITF-high/pigmentation
      tumour molecular subtype in a large cohort (120) of melanoma cell lines.
      Interestingly, CITED1 overexpression significantly suppressed MITF promoter
      activation, mRNA and protein expression levels while MITF was transiently
      upregulated following siRNA mediated CITED1 silencing. Conversely, MITF siRNA
      silencing resulted in CITED1 downregulation indicating a reciprocal relationship.
      Whole genome expression analysis identified a phenotype shift induced by CITED1
      silencing and driven mainly by expression of MITF and a cohort of MITF target
      genes that were significantly altered. Concomitantly, we found changes in the
      cell-cycle profile that manifest as transient G1 accumulation, increased
      expression of CDKN1A and a reduction in cell viability. Additionally, we could
      predict survival outcome by classifying primary melanoma tumours using our in
      vitro derived 'CITED1-silenced' gene expression signature. We hypothesize that
      CITED1 acts a regulator of MITF, functioning to maintain MITF levels in a range
      compatible with tumourigenesis. 

PMID- 25755925
TI  - Knowledge of malaria prevention among pregnant women and female caregivers of
      under-five children in rural southwest Nigeria.
AB  - Introduction. The morbidity and mortality from malaria are still unacceptably
      high in the developing countries, especially among the vulnerable groups like
      pregnant women and under-five children, despite all control efforts. The
      knowledge about the preventive measures of malaria is an important preceding
      factor for the acceptance and use of malaria preventive measures like Insecticide
      Treated Nets (ITN) by community members. Therefore, this study assessed the
      knowledge of malaria prevention among caregivers of under-five children and
      pregnant women in a rural community in Southwest Nigeria. Methodology. This is
      part of a larger malaria prevention study in rural Southwest Nigeria. A
      descriptive cross-sectional survey was conducted among pregnant women and
      caregivers of under-five children in Igbo-Ora, a rural town in Southwest Nigeria
      using a semi-structured, interviewer-administered questionnaire. Information was
      obtained on knowledge of malaria prevention, and overall composite scores were
      computed for knowledge of malaria prevention and ITN use. Data were analyzed
      using SPSS version 16. Associations between variables were tested using a Chi
      square with the level of statistical significance set at 5%. Results. Of the 631
      respondents, 84.9% were caregivers of under-five children and 67.7% were married.
      Mean age was 27.7 +/- 6.3 years with 53.4% aged between 20 and 29 years. Majority
      (91.1%) had at least primary school education and 60.2% were traders. Overall,
      57.7% had poor knowledge of malaria prevention. A good proportion (83.5%) were
      aware of the use of ITN for malaria prevention while 30.6% had poor knowledge of
      its use. Respondents who were younger (<30 years), had at least primary education
      and earn <10,000/per month had significantly poor knowledge of ITN use in malaria
      prevention. Majority (60.0%) respondents had poor attitude regarding use of ITNs.
      Conclusion. This study showed that the knowledge of malaria prevention is still
      low among under-five caregivers and pregnant women in rural Southwest Nigeria
      despite current control measures. There is a need for concerted health education
      intervention to improve the knowledge of rural dwellers regarding malaria
      prevention, including the use of ITN. This will go a long way to improving the
      reported low level of ownership and utilization of ITN in the rural areas. 

PMID- 25755926
TI  - An assessment of fracture resistance of three composite resin core build-up
      materials on three prefabricated non-metallic posts, cemented in endodontically
      treated teeth: an in vitro study.
AB  - Endodontically treated teeth with excessive loss of tooth structure would require
      to be restored with post and core to enhance the strength and durability of the
      tooth and to achieve retention for the restoration. The non-metallic posts have a
      superior aesthetic quality. Various core build-up materials can be used to build
      up cores on the posts placed in endodontically treated teeth. These materials
      would show variation in their bonding with the non-metallic posts thus affecting
      the strength and resistance to fracture of the remaining tooth structure. Aims.
      The aim of the study was to assess the fracture resistance of three composite
      resin core build-up materials on three prefabricated non-metallic posts, cemented
      in extracted endodontically treated teeth. Material and Methods. Forty-five
      freshly extracted maxillary central incisors of approximately of the same size
      and shape were selected for the study. They were divided randomly into 3 groups
      of 15 each, depending on the types of non-metallic posts used. Each group was
      further divided into 3 groups (A, B and C) of 5 samples each depending on three
      core build-up material used. Student's unpaired 't' test was also used to analyse
      and compare each group with the other groups individually, and decide whether
      their comparisons were statistically significant. Results. Luxacore showed the
      highest fracture resistance among the three core build-up materials with all the
      three posts systems. Ti-core had intermediate values of fracture resistance and
      Lumiglass had the least values of fracture resistance. 

PMID- 25755927
TI  - Structure determination of Murine Norovirus NS6 proteases with C-terminal
      extensions designed to probe protease-substrate interactions.
AB  - Noroviruses are positive-sense single-stranded RNA viruses. They encode an NS6
      protease that cleaves a viral polyprotein at specific sites to produce mature
      viral proteins. In an earlier study we obtained crystals of murine norovirus
      (MNV) NS6 protease in which crystal contacts were mediated by specific insertion
      of the C-terminus of one protein (which contains residues P5-P1 of the NS6-7
      cleavage junction) into the peptide binding site of an adjacent molecule, forming
      an adventitious protease-product complex. We sought to reproduce this crystal
      form to investigate protease-substrate complexes by extending the C-terminus of
      NS6 construct to include residues on the C-terminal (P') side of the cleavage
      junction. We report the crystallization and crystal structure determination of
      inactive mutants of murine norovirus NS6 protease with C-terminal extensions of
      one, two and four residues from the N-terminus of the adjacent NS7 protein (NS6
      1', NS6 2', NS6 4'). We also determined the structure of a chimeric extended NS6
      protease in which the P4-P4' sequence of the NS6-7 cleavage site was replaced
      with the corresponding sequence from the NS2-3 cleavage junction (NS6 4' 2|3).The
      constructs NS6 1' and NS6 2' yielded crystals that diffracted anisotropically. We
      found that, although the uncorrected data could be phased by molecular
      replacement, refinement of the structures stalled unless the data were
      ellipsoidally truncated and corrected with anisotropic B-factors. These
      corrections significantly improved phasing by molecular replacement and
      subsequent refinement.The refined structures of all four extended NS6 proteases
      are very similar in structure to the mature MNV NS6-and in one case reveal
      additional details of a surface loop. Although the packing arrangement observed
      showed some similarities to those observed in the adventitious protease-product
      crystals reported previously, in no case were specific protease-substrate
      interactions observed. 

PMID- 25755928
TI  - Interethnic diversity of the CD209 (rs4804803) gene promoter polymorphism in
      African but not American sickle cell disease.
AB  - Elucidating the genomic diversity of CD209 gene promoter polymorphism could
      assist in clarifying disease pathophysiology as well as contribution to co
      morbidities. CD209 gene promoter polymorphism has been shown to be associated
      with susceptibility to infection. We hypothesize that CD209 mutant variants occur
      at a higher frequency among Africans and in sickle cell disease. We analyzed the
      frequency of the CD209 gene (rs4804803) in healthy control and sickle cell
      disease (SCD) populations and determined association with disease. Genomic DNA
      was extracted from blood samples collected from 145 SCD and 231 control Africans
      (from Mali), 331 SCD and 379 control African Americans and 159 Caucasians.
      Comparative analysis among and between groups was carried out by polymerase chain
      reaction-restriction fragment length polymorphism (PCR-RFLP). Per ethnic
      diversification, we found significant disparity in genotypic (23.4% versus 16.9%
      versus 3.2%) and allelic frequencies (48.7% versus 42.1% versus 19.8%) of the
      homozygote mutant variant of the CD209 (snp 309A/G) gene promoter between
      Africans, African Americans and Caucasians respectively. Comparative evaluation
      between disease and control groups reveal a significant difference in genotypic
      (10.4% versus 23.4%; p = 0.002) and allelic frequencies (39.7% versus 48.7%; p =
      0.02) of the homozygote mutant variant in African SCD and healthy controls
      respectively, an observation that is completely absent among Americans. Comparing
      disease groups, we found no difference in the genotypic (p = 0.19) or allelic (p
      = 0.72) frequencies of CD209 homozygote mutant variant between Africans and
      Americans with sickle cell disease. The higher frequency of CD209 homozygote
      mutant variants in the African control group reveals a potential impairment of
      the capacity to mount an immune response to infectious diseases, and possibly
      delineate susceptibility to or severity of infectious co-morbidities within and
      between groups. 

PMID- 25755929
TI  - Language workbench user interfaces for data analysis.
AB  - Biological data analysis is frequently performed with command line software.
      While this practice provides considerable flexibility for computationally savy
      individuals, such as investigators trained in bioinformatics, this also creates a
      barrier to the widespread use of data analysis software by investigators trained
      as biologists and/or clinicians. Workflow systems such as Galaxy and Taverna have
      been developed to try and provide generic user interfaces that can wrap command
      line analysis software. These solutions are useful for problems that can be
      solved with workflows, and that do not require specialized user interfaces.
      However, some types of analyses can benefit from custom user interfaces. For
      instance, developing biomarker models from high-throughput data is a type of
      analysis that can be expressed more succinctly with specialized user interfaces.
      Here, we show how Language Workbench (LW) technology can be used to model the
      biomarker development and validation process. We developed a language that models
      the concepts of Dataset, Endpoint, Feature Selection Method and Classifier. These
      high-level language concepts map directly to abstractions that analysts who
      develop biomarker models are familiar with. We found that user interfaces
      developed in the Meta-Programming System (MPS) LW provide convenient means to
      configure a biomarker development project, to train models and view the
      validation statistics. We discuss several advantages of developing user
      interfaces for data analysis with a LW, including increased interface
      consistency, portability and extension by language composition. The language
      developed during this experiment is distributed as an MPS plugin (available at
      http://campagnelab.org/software/bdval-for-mps/). 

PMID- 25755930
TI  - Oxygen availability is a major factor in determining the composition of microbial
      communities involved in methane oxidation.
AB  - We have previously observed that methane supplied to lake sediment microbial
      communities as a substrate not only causes a response by bona fide methanotrophic
      bacteria, but also by non-methane-oxidizing bacteria, especially by members of
      the family Methylophilaceae. This result suggested that methane oxidation in this
      environment likely involves communities composed of different functional guilds,
      rather than a single type of microbe. To obtain further support for this concept
      and to obtain further insights into the factors that may define such
      partnerships, we carried out microcosm incubations with sediment samples from
      Lake Washington at five different oxygen tensions, while methane was supplied at
      the same concentration in each. Community composition was determined through 16S
      rRNA gene amplicon sequencing after 10 and 16 weeks of incubation. We demonstrate
      that, in support of our prior observations, the methane-consuming communities
      were represented by two major types: the methanotrophs of the family
      Methylococcaceae and by non-methanotrophic methylotrophs of the family
      Methylophilaceae. However, different species persisted under different oxygen
      tensions. At high initial oxygen tensions (150 to 225 uM) the major players were,
      respectively, species of the genera Methylosarcina and Methylophilus, while at
      low initial oxygen tensions (15 to 75 uM) the major players were Methylobacter
      and Methylotenera. These data suggest that oxygen availability is at least one
      major factor determining specific partnerships in methane oxidation. The data
      also suggest that speciation within Methylococcaceae and Methylophilaceae may be
      driven by niche adaptation tailored toward specific placements within the oxygen
      gradient. 

PMID- 25755931
TI  - Paleoneuroanatomy of the European lambeosaurine dinosaur Arenysaurus ardevoli.
AB  - The neuroanatomy of hadrosaurid dinosaurs is well known from North America and
      Asia. In Europe only a few cranial remains have been recovered that include the
      braincase. Arenysaurus is the first European endocast for which the
      paleoneuroanatomy has been studied. The resulting data have enabled us to draw
      ontogenetic, phylogenetic and functional inferences. Arenysaurus preserves the
      endocast and the inner ear. This cranial material was CT scanned, and a 3D-model
      was generated. The endocast morphology supports a general pattern for
      hadrosaurids with some characters that distinguish it to a subfamily level, such
      as a brain cavity that is anteroposteriorly shorter or the angle of the major
      axis of the cerebral hemisphere to the horizontal in lambeosaurines. Both these
      characters are present in the endocast of Arenysaurus. Osteological features
      indicate an adult ontogenetic stage, while some paleoneuroanatomical features are
      indicative of a subadult ontogenetic stage. It is hypothesized that the presence
      of puzzling mixture of characters that suggest different ontogenetic stages for
      this specimen may reflect some degree of dwarfism in Arenysaurus. Regarding the
      inner ear, its structure shows differences from the ornithopod clade with respect
      to the height of the semicircular canals. These differences could lead to a
      decrease in the compensatory movements of eyes and head, with important
      implications for the paleobiology and behavior of hadrosaurid taxa such as
      Edmontosaurus, Parasaurolophus and Arenysaurus. The endocranial morphology of
      European hadrosaurids sheds new light on the evolution of this group and may
      reflect the conditions in the archipelago where these animals lived during the
      Late Cretaceous. 

PMID- 25755932
TI  - Wild plant species growing closely connected in a subalpine meadow host distinct
      root-associated bacterial communities.
AB  - Plant roots are known to harbor large and diverse communities of bacteria. It has
      been suggested that plant identity can structure these root-associated
      communities, but few studies have specifically assessed how the composition of
      root microbiota varies within and between plant species growing under natural
      conditions. We assessed the community composition of endophytic and epiphytic
      bacteria through high throughput sequencing using 16S rDNA derived from root
      tissues collected from a population of a wild, clonal plant (Orange hawkweed
      Pilosella aurantiaca) as well as two neighboring plant species (Oxeye daisy
      Leucanthemum vulgare and Alsike clover-Trifolium hybridum). Our first goal was to
      determine if plant species growing in close proximity, under similar
      environmental conditions, still hosted unique root microbiota. Our results showed
      that plants of different species host distinct bacterial communities in their
      roots. In terms of community composition, Betaproteobacteria (especially the
      family Oxalobacteraceae) were found to dominate in the root microbiota of L.
      vulgare and T. hybridum samples, whereas the root microbiota of P. aurantiaca had
      a more heterogeneous distribution of bacterial abundances where
      Gammaproteobacteria and Acidobacteria occupied a larger portion of the community.
      We also explored the extent of individual variance within each plant species
      investigated, and found that in the plant species thought to have the least
      genetic variance among individuals (P. aurantiaca) still hosted just as diverse
      microbial communities. Whether all plant species host their own distinct root
      microbiota and plants more closely related to each other share more similar
      bacterial communities still remains to be fully explored, but among the plants
      examined in this experiment there was no trend that the two species belonging to
      the same family shared more similarities in terms of bacterial community
      composition. 

PMID- 25755933
TI  - Mammals from 'down under': a multi-gene species-level phylogeny of marsupial
      mammals (Mammalia, Metatheria).
AB  - Marsupials or metatherians are a group of mammals that are distinct in giving
      birth to young at early stages of development and in having a prolonged
      investment in lactation. The group consists of nearly 350 extant species,
      including kangaroos, koala, possums, and their relatives. Marsupials are an old
      lineage thought to have diverged from early therian mammals some 160 million
      years ago in the Jurassic, and have a remarkable evolutionary and biogeographical
      history, with extant species restricted to the Americas, mostly South America,
      and to Australasia. Although the group has been the subject of decades of
      phylogenetic research, the marsupial tree of life remains controversial, with
      most studies focusing on only a fraction of the species diversity within the
      infraclass. Here we present the first Methaterian species-level phylogeny to
      include 80% of the extant marsupial species and five nuclear and five
      mitochondrial markers obtained from Genbank and a recently published retroposon
      matrix. Our primary goal is to provide a summary phylogeny that will serve as a
      tool for comparative research. We evaluate the extent to which the phylogeny
      recovers current phylogenetic knowledge based on the recovery of "benchmark
      clades" from prior studies-unambiguously supported key clades and undisputed
      traditional taxonomic groups. The Bayesian phylogenetic analyses recovered nearly
      all benchmark clades but failed to find support for the suborder Phalagiformes.
      The most significant difference with previous published topologies is the support
      for Australidelphia as a group containing Microbiotheriidae, nested within
      American marsupials. However, a likelihood ratio test shows that alternative
      topologies with monophyletic Australidelphia and Ameridelphia are not
      significantly different than the preferred tree. Although further data are needed
      to solidify understanding of Methateria phylogeny, the new phylogenetic
      hypothesis provided here offers a well resolved and detailed tool for comparative
      analyses, covering the majority of the known species richness of the group. 

PMID- 25755935
TI  - Patient exposure in the basic science classroom enhances differential diagnosis
      formation and clinical decision-making.
AB  - Purpose. The authors proposed that introducing real patients into a pathology
      classroom early in medical education would help integrate fundamental principles
      and disease pathology with clinical presentation and medical history. Methods.
      Three patients with different pathologies described their history and
      presentation without revealing their diagnosis. Students were required to submit
      a differential diagnosis in writing, and then were able to ask questions to
      arrive at the correct diagnosis. Students were surveyed on the efficacy of
      patient-based learning. Results. Average student scores on the differential
      diagnosis assignments significantly improved 32% during the course. From the
      survey, 72% of students felt that patient encounters should be included in the
      pathology course next year. Seventy-four percent felt that the differential
      diagnosis assignments helped them develop clinical decision-making skills.
      Seventy-three percent felt that the experience helped them know what questions to
      ask patients. Eighty-six percent felt that they obtained a better understanding
      of patients' social and emotional challenges. Discussion. Having students work
      through the process of differential diagnosis formulation when encountering a
      real patient and their clinical presentation improved clinical decision-making
      skills and integrated fundamental concepts with disease pathology during a basic
      science pathology course. 

PMID- 25755934
TI  - Genetic divergence between populations of feral and domestic forms of a mosquito
      disease vector assessed by transcriptomics.
AB  - Culex pipiens, an invasive mosquito and vector of West Nile virus in the US, has
      two morphologically indistinguishable forms that differ dramatically in behavior
      and physiology. Cx. pipiens form pipiens is primarily a bird-feeding temperate
      mosquito, while the sub-tropical Cx. pipiens form molestus thrives in sewers and
      feeds on mammals. Because the feral form can diapause during the cold winters but
      the domestic form cannot, the two Cx. pipiens forms are allopatric in northern
      Europe and, although viable, hybrids are rare. Cx. pipiens form molestus has
      spread across all inhabited continents and hybrids of the two forms are common in
      the US. Here we elucidate the genes and gene families with the greatest
      divergence rates between these phenotypically diverged mosquito populations, and
      discuss them in light of their potential biological and ecological effects. After
      generating and assembling novel transcriptome data for each population, we
      performed pairwise tests for nonsynonymous divergence (Ka) of homologous coding
      sequences and examined gene ontology terms that were statistically over
      represented in those sequences with the greatest divergence rates. We identified
      genes involved in digestion (serine endopeptidases), innate immunity (fibrinogens
      and alpha-macroglobulins), hemostasis (D7 salivary proteins), olfaction (odorant
      binding proteins) and chitin binding (peritrophic matrix proteins). By examining
      molecular divergence between closely related yet phenotypically divergent forms
      of the same species, our results provide insights into the identity of rapidly
      evolving genes between incipient species. Additionally, we found that families of
      signal transducers, ATP synthases and transcription regulators remained identical
      at the amino acid level, thus constituting conserved components of the Cx.
      pipiens proteome. We provide a reference with which to gauge the divergence
      reported in this analysis by performing a comparison of transcriptome sequences
      from conspecific (yet allopatric) populations of another member of the Cx.
      pipiens complex, Cx. quinquefasciatus. 

PMID- 25755937
TI  - European journal of pediatric surgery reports.

PMID- 25755936
TI  - Child Welfare Involved Caregiver Perceptions of Family Support in Child Mental
      Health Treatment.

PMID- 25755938
TI  - Diagnosis and management of an isolated pediatric plexiform neurofibroma
      involving the hepatic and celiac plexus using multimodality approach: problem
      solving with diffusion-weighted magnetic resonance imaging.
AB  - Plexiform neurofibroma with involvement of the gastrointestinal tract is a very
      rare entity in children. Here, we present a rather unique case of a 9-year-old
      boy with no clinical signs or features of neurofibromatosis type 1. A periportal
      mass lesion was incidentally found after performing an ultrasound in this
      previously healthy child. Computed tomographic scan was subsequently performed
      which showed a low-density mass in a periportal distribution with extension along
      the celiac axis. Because the findings were nonspecific, a pre- and postcontrast
      magnetic resonance imaging of the abdomen was performed which included diffusion
      weighted imaging. The lesion was then confirmed to be a plexiform neurofibroma
      with open biopsy. Management of plexiform neurofibromas varies widely. Given the
      extensive nature of the lesion, managing the patient with follow-up rather than
      surgical excision was favored. 

PMID- 25755939
TI  - Intestinal perforation in the context of thoracoamniotic shunting and congenital
      diaphragmatic hernia.
AB  - A fetus was diagnosed by prenatal ultrasound with bilateral intrauterine pleural
      effusions that were subsequently drained in utero by insertion of bilateral
      thoracoamniotic shunts. Serial prenatal ultrasound scans were consistent with a
      left-sided diaphragmatic hernia. On the first day of life, the infant underwent
      an exploratory laparotomy for intestinal obstruction, with radiographic findings
      of pneumatosis intestinalis. Intraoperative findings were suggestive of prenatal
      bowel and diaphragm perforation, which might have occurred as a complication of
      thoracoamniotic shunting. 

PMID- 25755940
TI  - First case report of single port video-assisted thoracoscopic middle lobectomy
      for the treatment of pulmonary aspergilloma in a pediatric patient.
AB  - We present the case of an 11-year-old girl with pulmonary aspergilloma secondary
      to a hematologic disease successfully treated with a single port video-assisted
      thoracoscopic lobectomy. This surgical procedure was not previously reported. We
      consider this approach to be a safe and appropriate procedure for lung resection,
      in children or adults requiring minimal intervention and early recovery. 

PMID- 25755941
TI  - Right bochdalek hernia associated with kartagener syndrome: developmental and
      clinical observations.
AB  - We present a novel case of the association of right-sided Bochdalek hernia, a
      diaphragmatic life-threatening malformation, and Kartagener syndrome, which is
      characterized by congenital bronchiectasis, chronic sinusitis, and situs
      inversus. The developmental and clinical findings are discussed. When an
      association of diaphragmatic hernia with situs viscerum inversus is encountered,
      physicians should be mindful of the possibility of Kartagener syndrome because
      this condition could significantly affect the morbidity of the patient. 

PMID- 25755942
TI  - A Rare Case of Chylothorax due to Pulmonary Lymphangiectasia in a 7-Year-Old Boy.
AB  - Pulmonary lymphangiectasia (PL) is a rare condition characterized by dilatation
      of the lymphatic vessels. Post-neonatal PL is usually associated with pleural
      effusion and should therefore be suspected in the presence of chylothorax. We
      describe a post-neonatal manifestation of PL in a 7-year-old boy presenting
      chylothorax. Radiological examinations included thorax X-ray, ultrasound, and
      computed tomography scans. After the failure of conservative management
      (maintenance of the chest tube, total parenteral nutrition, administration of
      somatostatin synthetic analogues) we performed a thoracoscopic massive ligation
      of the thoracic duct's collateral along with a lung biopsy. Histology was
      compatible with type 1 congenital pulmonary lymphangectasia. One month after
      surgery a thoracoscopic pleurodesis was required for persistent chylothorax. The
      boy is now doing well 1 year after surgery. 

PMID- 25755943
TI  - Iatrogenic perforation of upper pouch in pure esophageal atresia: a rare
      complication and review of literature.
AB  - Iatrogenic perforation of the neonate's pharynx and esophagus with normal anatomy
      was first described by Eklof et al in 1968. It typically occurs in severely
      premature neonates who have undergone repeated traumatic attempts at endotracheal
      intubation or passage of orogastric tubes. It may also mimic esophageal atresia
      (EA). Perforation of upper pouch in tracheoesophageal fistula with EA was rarely
      reported. We report a 1,400 g (32 weeks) neonate with pure EA and iatrogenic
      perforation of upper pouch due to use of catheter for diagnostic radiography. 

PMID- 25755944
TI  - Use of Mitomycin C for Refractory Esophageal Stricture following
      Tracheoesophageal Fistula Repair.
AB  - Esophageal stricture is a well-described complication following tracheoesophageal
      fistula repair. Herein, we report two patients who had persistent esophageal
      strictures after several months of repeat balloon dilatations. Each patient was
      treated with a single application of topical mitomycin C in addition to
      esophageal dilatation, which resulted in complete resolution of the stricture. 

PMID- 25755945
TI  - Clinico-radiological diagnosis of isolated congenital esophageal stenosis in a
      preterm neonate.
AB  - A 2-day-old preterm female neonate weighing 1.6 kg and having excessive frothing
      from mouth was investigated for suspected esophageal atresia and
      tracheoesophageal fistula. X-ray findings of an unusually low-ending upper pouch
      (up to T8 level) and the absence of gas in abdomen lead to suspicion of an
      unusual variety of esophageal atresia. Hence unlike the usual management of pure
      esophageal atresia, in terms of esophagostomy and gastrostomy in neonatal period,
      right thoracotomy was performed allowing successful primary anastomosis. A high
      index of suspicion on the basis of radiological picture led to early diagnosis of
      a rare anomaly like congenital esophageal stenosis and successful management of
      this low birth weight baby. 

PMID- 25755946
TI  - Neonatal intestinal perforation-a rare complication of small bowel hemangioma.
AB  - Intestinal perforation is an extremely rare complication of hemangioma of the
      small intestine in the neonatal period. This is a case report of a 27-days-old
      male infant who presented with signs and symptoms of acute intestinal
      obstruction. Exploratory laparotomy findings revealed intestinal perforation due
      to solitary hemangioma in the ileum, which led to obstruction from peritoneal
      reaction and adhesions. There are two reported cases in the literature presenting
      with ileal perforation in the pediatric age group, but only one previous report
      mentioned in the neonatal period. Because there are other more common causes of
      perforation in the neonatal period, intestinal hemangioma in spite of its rarity
      should be included in the differential diagnosis. 

PMID- 25755947
TI  - Abdominal cystic lymphangioma mimicking appendicitis.
AB  - A cystic lymphangioma arising within the abdomen is a rare entity in children. It
      may present with an abdominal mass and symptoms of abdominal pain, vomiting, and
      anorexia. These nonspecific clinical symptoms are often attributed to more common
      acute pediatric conditions. In this report, we describe two pediatric cases of
      intra-abdominal cystic lymphangioma that were initially diagnosed and treated as
      appendicitis. True diagnosis was only achieved on surgical excision and
      pathological investigation of cystic material. 

PMID- 25755948
TI  - Secondary omental torsion as a rare cause of acute abdomen in a child and the
      advantages of laparoscopic approach.
AB  - Omental torsion is an underdiagnosed cause of acute abdomen in children. Most
      cases occur in adults, with only 15% presenting in children. It is estimated that
      omental infarct is found in approximately 0.1 to 0.5% of children undergoing
      operations for appendicitis. It may present with various signs and symptoms,
      although the clinical presentation usually mimics that of acute appendicitis.
      Definitive diagnosis is often established during surgery. We report a case of a 9
      year-old boy who came to our attention for acute abdomen. We performed a
      laparoscopy-assisted procedure suspecting acute appendicitis. We therefore
      identified a secondary omental torsion associated with patency of the right
      inguinal duct and herniated omentum. Laparoscopy allowed a correct diagnosis and
      therapy. 

PMID- 25755949
TI  - Proteus syndrome: report of intra-abdominal lipomatosis.
AB  - Proteus syndrome (PS) is an extremely rare sporadic disorder that manifests as an
      asymmetric, disproportionate overgrowth of any connective tissues, such as bone,
      fat, or epidermal nevi, in a mosaic or patchy pattern. This hamartoneoplastic
      syndrome was first described by Cohen and Hayden. Its prevalence is approximately
      1 per 1,000,000 live births, and intra-abdominal expansion has been reported in
      no more than 20 cases in the literature. The phenotypes of the patients differ
      because of the variation in the pattern of the overgrowths, making diagnosis
      difficult. Extremely large subcutaneous lipomas and internal lipomas, which occur
      rarely, are one of the presentation phenotypes. Here, we present the second
      patient in the literature with PS involving the epiploon. 

PMID- 25755950
TI  - An unusual localization of the umbilicus in a neonate.
AB  - We report the case of a male neonate with a low-set umbilicus. Physical
      examination revealed an appropriately grown term infant with no unusual findings,
      except ectopically placed umbilical cord at the level of the bladder in the
      hypogastric zone. The infant underwent detailed investigations that revealed no
      associated malformation. To the best of our knowledge, this is the first case
      with very distinct localization of the umbilicus without any congenital
      abnormalities. 

PMID- 25755951
TI  - Recurrent Cholangitis with Congenital Hepatic Fibrosis and Pancreaticobiliary
      Maljunction after Roux-en-Y Reconstruction.
AB  - A 1-year-old girl had pancreaticobiliary maljunction, a choledochal cyst, and
      polycystic kidney. At the age of 4 years, she was treated by resection of the
      choledochal cyst and Roux-en-Y reconstruction because of the cyst's risk of
      cancer. She was diagnosed as having congenital hepatic fibrosis based on the
      histological findings. Postoperatively, she suffered recurrent fever of unknown
      origin, refractory to several antibiotics. At the age of 6 years, she underwent
      living donor liver transplantation from her father. Multi-drug-resistant
      Pseudomonas aeruginosa was cultured in the recipient's liver. After liver
      transplantation, she had no episodes of recurrent fever. Roux-en-Y reconstruction
      should be avoided for ductal plate malformations such as congenital hepatic
      fibrosis. 

PMID- 25755952
TI  - Endoscopically placed rectourethral guidewire facilitates the reconstruction of
      anus in children with anorectal malformations: a case report.
AB  - The aim of this report is to present a technical detail of use in the management
      of an anorectal malformation (ARM). A boy with ARM and a fistula to the urethra
      was operated on with a posterior sagittal anorectoplasty (PSARP). Before the
      PSARP operation, a videoendoscopy was performed through the distal stoma down to
      the distal end of the rectum. The rectourethral fistula was identified and a
      guidewire was passed through the endoscope, through the fistula, and out through
      the urethra. The endoscopically placed rectourethral guidewire was used as a
      landmark and facilitated the PSARP operation. 

PMID- 25755953
TI  - Transverse colonic volvulus in a child: successful management with decompression
      and delayed laparoscopic colopexy.
AB  - We report a case of colonic volvulus in a 7-year-old child with normal
      development. Operative findings at laparotomy showed a 270-degree transverse
      colonic volvulus (TCV), with colonic ligamentous attachment abnormalities. A loop
      ileostomy was formed following detorsion, with delayed laparoscopic colopexy.
      This is the first case to describe decompression by diversion ileostomy as acute
      management of TCV with delayed laparoscopic colopexy, so avoiding unnecessary
      bowel resection. 

PMID- 25755954
TI  - Giant presacral tailgut cyst mimicking rectal duplication in a girl: report of a
      pediatric case.
AB  - Tailgut cyst, or retrorectal cystic hamartoma, is a rare congenital lesion found
      in the presacral space. The lession has been infrequently reported in medical
      literature. It is most common in middle-aged women and is rare in children. We
      report a case of a tailgut cyst mimicking a rectal duplication in an 8-year-old
      child. Excision and histological examination of the mass confirmed the tailgut
      cyst. 

PMID- 25755955
TI  - Steroid treatment for recurrent epididymitis secondary to idiopathic urethritis
      and urethrovasal reflux.
AB  - We describe a case of recurrent left-sided epididymitis secondary to severe
      idiopathic posterior urethritis extending to left seminal vesicle and vas
      deference with associated urethrovasal reflux (UVR). Cystourethroscopy and
      micturating cystourethrogram were essential for the diagnosis. Following
      cystourethroscopy, intravesical, and urethral instillation of topical steroid
      triamcinolone, patient had a full recovery. Idiopathic urethritis in association
      with veru montentitis, utriculitis leading to left-sided UVR, inflammation of the
      seminal vesicle, and vas deference causing secondary epididymitis is rare. We
      report the first such rare case presenting as recurrent acute scrotum and
      response to innovative treatment we used. 

PMID- 25755956
TI  - Foreign Body Reaction with High Standard Uptake Value Level in 18-FDG PET/CT
      Mimicking Relapse in an 8-Year-Old Patient Diagnosed with Hodgkin Lymphoma: A
      Case Report.
AB  - Combined positron emission tomography and computed tomography (PET/CT) using 18
      fluorodeoxyglucose (18-FDG) is one of the most effective methods to identify
      pathological lymph node involvement. We report the case of a child who underwent
      cervical lymph node biopsy and chemotherapy for Hodgkin disease. Three years
      after surgery, PET/CT identified an intense localization of 18-FDG in the
      inferior cervical region. This finding led to a reexcision of the mass. The only
      finding was a granuloma arising in reaction to a hemostatic sponge. 

PMID- 25755957
TI  - The First 2 Years of EJPS Reports.

PMID- 25755958
TI  - Pancreatic kaposiform hemangioendothelioma presenting with duodenal obstruction
      and kasabach-merritt phenomenon: a neonate cured by whipple operation.
AB  - Aim Kaposiform hemangiondothelioma (KHE) is a rare vascular tumor, commonly
      associated with Kasaback-Merritt phenomenon characterized by thrombocytopenia and
      consumptive coagulopathy. We report a case of pancreatic KHE presenting with
      neonatal duodenal obstruction and Kasaback-Merritt phenomenon. Case Report A full
      term male baby presented with bile stained vomiting on Day 3 of life. Contrast
      study and computed tomography scan showed duodenal obstruction by a 5 cm
      extrinsic hypervascular mass. Platelet count was 23 x 109/L. Laparotomy confirmed
      a vascular tumor arising from the pancreatic head compressing on the duodenum.
      Whipple operation was performed. Results Intestinal obstruction and
      thrombocytopenia resolved after surgery. There was no post-operative
      complications. Histology confirmed KHE. The boy was tolerating hydrolyzed milk
      formula and was thriving at 5 months follow up. Conclusion We reported a case of
      pancreatic KHE presented with neonatal intestinal obstruction and Kasaback
      Merritt phenomenon. High index of suspicion is necessary for diagnosis. To our
      knowledge, this is the youngest patient who underwent Whipple operation. 

PMID- 25755959
TI  - Laparoscopic gastroscopic transgastric cystogastrostomy and cholecystectomy for
      pseudopancreatic cyst after gallstone pancreatitis in children.
AB  - A 15-year-old girl presented with gallstone pancreatitis. Subsequently, a
      pseudopancreatic cyst developed that was diagnosed on computed tomographic scan.
      She underwent a laparoscopic and gastroscopic transgastric cystogastrostomy. In
      the following report, we describe our novel approach and technique for the above
      condition. 

PMID- 25755960
TI  - Cephalic pancreaticoduodenectomy for bleeding duodenal arteriovenous
      malformation.
AB  - Introduction Treatment of recurrent severe gastrointestinal bleeding due to
      arteriovenous malformations may require complex resections. In some particular
      locations, extensive surgery is the only way out, as shown in this report. Case
      Report A 2.5-year-old child suffered repeated episodes of upper gastrointestinal
      bleeding since the first month of life. After an extensive diagnostic workout,
      the diagnosis of duodenal arteriovenous malformation was established. Cephalic
      pancreaticoduodenectomy with pyloric preservation was performed and no further
      episodes of bleeding occurred in the ensuing 2 years. Conclusion Bleeding
      malformations located in the pancreaticoduodenal area can be effectively treated
      in children by pylorus-preserving cephalic pancreaticoduodenectomy. 

PMID- 25755961
TI  - Inflammatory fibroid polyp: a rare benign tumor of the alimentary tract in
      children presenting as intussusception-case report and review of literature.
AB  - Inflammatory fibroid polyp (IFP) represents a rare cause of gastrointestinal
      polypoid disease in childhood. Tauhe lesion has been described by various names
      beyond the currently accepted term, including "Vanek's tumour," eosinophilic or
      submucosal granuloma, gastric fibroma with eosinophilic infiltration,
      inflammatory pseudotumor, and hemangiopericytoma. The etiopathogenesis and origin
      of the mesenchymal spindle-shaped cells that comprise the polyp remains
      enigmatic. Recent studies have shown familial occurrence, expression of platelet
      derived growth factor receptor (PDGFRA) and oncogenic PDGFRA mutations in the
      majority of lesions, suggestive of a neoplastic nature. We present a rare case of
      a 10-year-old boy with an IFP of the terminal ileum, who presented acutely with
      intussusception and was treated with a right hemicolectomy. Postoperative course
      was uneventful and the patient has been asymptomatic during follow-up.
      Histopathology and immunohistochemical analysis excluded inflammatory
      myofibroblastic tumor (negative for Alk1, desmin, smooth muscle actin [SMA]),
      gastrointerstinal stromal tumors (GIST) (negative for CD117) and schwannoma
      (negative for S100). The lesion was positive for CD34 and faintly for vimentin.
      Despite the classification of IFPs as a mesenchymal benign neoplasm, in the vast
      majority of cases, surgical excision alone was curative, and no reports exist of
      a malignant transformation. A cautious approach with periodic surveillance of the
      affected children seems reasonable though. 

PMID- 25755962
TI  - An Interesting Case of Double Compound Intussusception without Intestinal
      Occlusion in a 5-Year-Old Boy.
AB  - Intussusception is a very common surgical finding in children. Idiopathic
      intussusception is relatively frequent in children within the first year and it
      usually causes an acute abdomen. Instead, complex intussusception involving
      multiple or remote intestinal segments is a very rare entity and it is frequently
      diagnosed intraoperatively. It is often because of an anatomical cause and it can
      occur at any age. We report a unique case of contemporary double site anterograde
      and retrograde ileoileal intussusception without intestinal occlusion because of
      a submucous intestinal lipoma. In our case, imaging studies were important for
      clinical suspicion and laparoscopy was essential for final diagnosis and its
      resolution. 

PMID- 25755963
TI  - Single-incision laparoscopic splenectomy and splenic autotransplantation for an
      enlarged wandering spleen with torsion.
AB  - A wandering spleen is a rare condition in which the spleen is not located in the
      left upper quadrant, but instead is found in the lower abdomen or in the pelvic
      region because of the laxity of the peritoneal attachments. The unusually long
      pedicle is susceptible to twisting, which can lead to ischemia, and eventually to
      necrosis. We herein report a case of an enlarged wandering spleen with torsion,
      successfully treated by single-incision laparoscopic splenectomy and
      autotransplantation. The transplanted splenic tissues could be identified on a
      spleen scintigram obtained 3 months after the surgery. Howell-Jolly bodies were
      not observed in blood specimens. This procedure is able to prevent an
      overwhelming postsplenectomy infection, and leads to satisfactory cosmetic
      results. 

PMID- 25755964
TI  - Splenorenal collaterals as hallmark for a twisted wandering spleen in a 14-year
      old girl with abdominal pain: a case report.
AB  - Wandering spleen is a rare cause of acute or chronic recurrent abdominal pain
      with a risk of splenic torsion and infarction. We describe a case of a 14-year
      old girl with chronic recurrent abdominal pain with a palpable spleen in normal
      position on the initial physical examination. Laboratory findings were normal. A
      normal blood flow was seen on the initial (color Doppler) sonography. Magnetic
      resonance imaging showed an enlarged spleen in the pelvic region with torsion of
      hilar pedicle and splenorenal collaterals. Semielective, a laparoscopic
      splenopexy was performed without complications. A twisted wandering spleen should
      be included in the differential diagnosis of recurrent abdominal pain despite
      possible normal positioning of the spleen. The presence of splenorenal
      collaterals on imaging techniques can be used as a diagnostic hallmark. 

PMID- 25755965
TI  - An unusual cause of protein losing enteropathy in a 2.5-year-old girl: meso
      intestinal fibrosis.
AB  - Introduction Protein losing enteropathy is a symptom characterized by loss of
      protein in intestines resulting in low protein levels in serum and generalized
      edema. Several causes are reported for this condition. Hereby we report an as yet
      unreported cause of protein losing enteropathy that we named meso-intestinal
      fibrosis. Case Report A 2.5-year-old girl referred with features of partial
      intestinal obstruction and underwent laparotomy. She had history of protein
      losing enteropathy since 16 months of age with generalized edema and received
      albumin every other week. Workup of protein losing enteropathy was inconclusive
      and only a histology report denoted increase in eosinophils in lamina propria of
      small intestine and hypoallergenic diet was started for her, but no significant
      response was noted. Laparotomy revealed lace-like white areas in meso of small
      intestine and intestinal wall was firm in palpation in some areas. Biopsy was
      taken from these sites and histology revealed severe fibrosis of meso overlying
      muscularis propria and also patchy fibrosis of intestinal meso led to severe
      lymphangiectasis in submucosa of small intestine. Discussion Secondary
      lymphangiectasis due to obstruction of lymphatic flow is mentioned as cause of
      protein losing enteropathy. Meso-intestinal fibrosis seen in this case that led
      to secondary lymphangiectasis and also motility disorder has not been reported as
      yet. 

PMID- 25755966
TI  - Migration of indwelling central venous catheter and fatal hydrothorax.
AB  - Central venous catheter complications can be related to insertion, indwelling, or
      extraction. Most of the times, immediate complications are anticipated and
      managed; whereas, delayed complications can go unnoticed. In the case discussed
      here, migration and dislodgement of catheter tip resulted in delayed hydrothorax
      and sudden death of a 9-month-old female infant. 

PMID- 25755967
TI  - Congenital trifurcation of the trachea.
AB  - "Tracheal trifurcation" is a veritable and rare finding. We illustrate a unique
      case that demonstrates the complexity and broad variability that congenital
      tracheobronchial anomalies can take. Appreciation of these is important at
      intubation, bronchoscopy, and surgery. 

PMID- 25755968
TI  - Recurrent hemoptysis and a mass in the thorax in an infant: the split notochord
      syndrome.
AB  - Split notochord syndrome is a rare group of developmental abnormalities caused by
      abnormal splitting or deviation of the notochord clinically resulting in the
      duplicated bowel associated with vertebral anomalies. We report on a case of 11
      month-old female infant with mediastinal hyperechogenic cyst and intestinal
      duplication cyst associated with T5-T6 hemivertebrae, scoliosis, and nonfusion of
      posterior part of T6 vertebrae, presenting with severe hemoptysis and
      hematemesis. The cysts were surgically removed, and histopathologic analysis
      revealed that the mediastinal cyst was lined by gastric mucosa and intestinal one
      was lined with gastric mucosa including ectopic pancreatic tissue. After removal
      of the lesion the patient made an uneventful recovery and shows no signs of long
      term pulmonary sequelae. 

PMID- 25755969
TI  - Pulmonary torsion as an atypical complication of congenital esophageal atresia
      repair-a case report and review of literature.
AB  - Pulmonary torsion is a severe, life-threatening event, rarely occurring in
      children. We present a case of atypical postoperative complication of esophageal
      atresia repair in the form of pulmonary torsion comprising the middle lobe of the
      right lung. Clinical deterioration in the face of normal arterial blood gases
      should rise a high index of suspicion for pulmonary torsion. Early diagnosis is
      crucial, treatment is surgical, detorsion if possible, or if the lobe is not
      viable-resection. 

PMID- 25755970
TI  - Mature cystic retroperitoneal teratoma with well differentiated renal elements:
      relation to spinal dysraphism.
AB  - Retroperitoneum is a relatively uncommon site for pediatric teratomas. Rarely,
      such tumors can have an intraspinal extension and few cases of retroperitoneal
      teratomas associated with spinal dysraphism have been reported. Teratomas consist
      of tissues arising from all three embryonic layers. However, mature renal tissues
      in the form of glomeruli and tubules are sparingly found in teratomas. A 15-day
      old female presented with spina bifida occulta and on evaluation a cystic
      presacral mass was detected. Intraoperatively the cyst was found densely adherent
      to the hemivertebrae but not entering the spinal canal. Histopathological
      examination confirmed a mature cystic teratoma but also demonstrated presence of
      mature renal elements in the cyst wall. The teratomas lying in proximity to spine
      and associated with spinal dysraphism are likely to contain mature renal tissues
      or even nephroblastic elements. It supports the dysembryogenic model of origin of
      intradural teratomas from native progenitor cells rather than aberrantly migrated
      germ cells. 

PMID- 25755971
TI  - Rare lipomatous tumor of the posterior mediastinum in children.
AB  - The mediastinum is a unique anatomic area containing various structures and
      pluripotent cells, which allow for the development of a range of tumors. We
      report two pediatric cases of a lipomatous tumor of the posterior mediastinum.
      Complete surgical excision of the mass in each was achieved through a lateral
      thoracotomy. Histopathologic findings showed a lipoma in one case and a
      lipoblastoma in the other. A lipomatous tumor in the posterior mediastinum is
      extremely rare and preoperative diagnosis is difficult. When an operative plan is
      being considered, the presence of a potentially malignant tumor should be kept in
      mind. 

PMID- 25755972
TI  - Inflammatory myofibroblastic tumor of the colon with an unusual presentation of
      intestinal intussusception.
AB  - Inflammatory myfibroblastic tumor (IMT), also known as inflammatory pseudotumor
      is unusual, benign solid tumor. This tumor is commonly reported in the lungs but
      can be present in extrapulmonary sites as well. We present the case of a 7-year
      old girl with IMT in an unusual location. The patient was admitted with abdominal
      pain, and ultrasound showed a solid mass in the abdomen. She was operated and
      colocolic intussusception secondary to a mass was found. Histologic evaluation of
      mass revealed IMT. 

PMID- 25755973
TI  - Spigelian hernia in a 14-year-old girl: a case report and review of the
      literature.
AB  - Spigelian hernia (SH) is a surgical rarity in children, which occurs through slit
      like defects in the anterior abdominal wall adjacent to the semilunar line, the
      convexity lateral line which joins the nine ribs to the pubic tubercle and signs
      the limit between the muscular and aponeurotic portion of transversus abdominis
      muscle. As there are no specific symptoms and signs, the diagnosis is difficult,
      especially in children. We report a case of SH that comes to our observation: a
      14-year-old girl presented recurrent abdominal pain associated to intermittent
      palpable mass in the paraumbilical region. Starting from our case report, we
      review the literature of pediatric SH from 2000 to 2013 and we describe the
      anatomy, etiology, clinical presentation, instrumental diagnosis, and surgical
      technique of pediatric SH. 

PMID- 25755974
TI  - Left-sided amyand hernia: report of two cases with review of literature.
AB  - The presence of the vermiform appendix in an inguinal hernial sac is called
      "Amyand" Hernia, which is a rare condition especially in children. The authors
      are reporting two cases of left-sided Amyand hernia in infants presented with
      symptoms and signs of obstructed inguinal hernia. Emergency appendectomy and
      herniotomy were performed. The patients were followed up for 4 to 6 months
      without complications. The case histories are presented, and the conditions
      discussed with review of the literature. 

PMID- 25755975
TI  - Abdominal Cellulitis following a Laparoscopic Procedure: A Rare and Severe
      Complication.
AB  - Advantages of laparoscopic approach in Hirschsprung disease have been already
      published decreasing the hospital stay and postoperative adhesions. To our
      knowledge, we report the first case of postoperative abdominal cellulitis after
      laparoscopic procedure. A laparoscopic Duhamel pull through was done on a 3-month
      old child. Full-thickness biopsy under laparoscopy was performed with
      intraperitoneal inoculation. Large peritoneal irrigation was used. Abdominal
      necrotizing cellulitis starting from a port site occurred few days after the
      procedure requiring repeat surgical excision, broad spectrum antibiotics, and
      hyperbaric oxygen. 

PMID- 25755976
TI  - Study of particle rearrangement, compression behavior and dissolution properties
      after melt dispersion of ibuprofen, Avicel and Aerosil.
AB  - Particle rearrangements, compaction under pressure and in vitro dissolution have
      been evaluated after melt dispersion of ibuprofen, Avicel and Aerosil. The Cooper
      Eaton and Kuno equations were utilized for the determination of particle
      rearrangement and compression behavior from tap density and compact data.
      Particle rearrangement could be divided into two stages as primary and secondary
      rearrangement. Transitional tapping between the stages was found to be 20-25 taps
      in ibuprofen crystalline powder, which was increased up to 45 taps with all
      formulated powders. Compaction in the rearrangement stages was increased in all
      the formulations with respect to pure ibuprofen. Significantly increased
      compaction of ibuprofen under pressure can be achieved using Avicel by melt
      dispersion technique, which could be beneficial in ibuprofen tablet manufacturing
      by direct compression. SEM, FTIR and DSC have been utilized for physicochemical
      characterization of the melt dispersion powder materials. Dissolution of
      ibuprofen from compacted tablet of physical mixture and melt dispersion particles
      has also been improved greatly in the following order:
      Ibc<Ibsmd1<Ibsmd2<Ibsmp10<Ibsmd5<Ibsmd10. 

PMID- 25755977
TI  - Stabilizing effect of citrate buffer on the photolysis of riboflavin in aqueous
      solution.
AB  - In the present investigation the photolysis of riboflavin (RF) in the presence of
      citrate species at pH 4.0-7.0 has been studied. A specific multicomponent
      spectrophotometric method has been used to assay RF in the presence of
      photoproducts during the reactions. The overall first-order rate constants (k obs
      ) for the photolysis of RF range from 0.42 to 1.08*10(-2) min(-1) in the region.
      The values of k obs have been found to decrease with an increase in citrate
      concentration indicating an inhibitory effect of these species on the rate of
      reaction. The second-order rate constants for the interaction of RF with total
      citrate species causing inhibition range from 1.79 to 5.65*10(-3) M(-1) min(-1)
      at pH 4.0-7.0. The log k-pH profiles for the reactions at 0.2-1.0 M citrate
      concentration show a gradual decrease in k obs and the value at 1.0 M is more
      than half compared to that of k 0, i.e., in the absence of buffer, at pH 5.0.
      Divalent citrate ions cause a decrease in RF fluorescence due to the quenching of
      the excited singlet state resulting in a decrease in the rate of reaction and
      consequently leading to the stabilization of RF solutions. The greater quenching
      of fluorescence at pH 4.0 compared to that of 7.0 is in accordance with the
      greater concentration of divalent citrate ions (99.6%) at that pH. The trivalent
      citrate ions exert a greater inhibitory effect on the rate of RF photolysis
      compared to that of the divalent citrate ions probably as a result of excited
      triplet state quenching. The values of second-order rate constants for the
      interaction of divalent and trivalent citrate ions are 0.44*10(-2) and 1.06*10(
      3) M(-1) min(-1), respectively, indicating that the trivalent ions exert a
      greater stabilizing effect, compared to the divalent ions, on RF solutions. 

PMID- 25755978
TI  - Comparative evaluation of humic substances in oral drug delivery.
AB  - Major and biologically most explored components of natural organic matter (NOM)
      are humic acid (HA) and fulvic acid (FA). We have explored rock shilajit as a
      source of NOM. On the other hand carbamazepine (CBZ) is a well known
      anticonvulsant drug and has a limited accessibility to brain. Bioavailability and
      pharmacokinetic profiles of CBZ have been improved by complexation and different
      techniques also. Present study has assessed the comparative abilities of FA and
      HA as complexing agent for CBZ in order to enhance pharmacokinetic profile of CBZ
      and accessibility to the brain. These two complexing agents have been compared on
      various indices such as their abilities to cause complexation and enhance
      solubility, permeability and dissolution. The present study also compared
      pharmacodynamic and biochemical profiles after oral administration of complexes.
      With the help of various pharmaceutical techniques such as freeze drying,
      physical mixture, kneading and solvent evaporation, two molar ratios (1:1 and
      1:2) were selected for complexation and evaluated for conformational analysis
      (molecular modeling). Complex formed was further characterized by differential
      scanning calorimetry (DSC), Fourier transform infrared spectroscopy (FT-IR), mass
      spectroscopy and X-ray diffraction (XRD). Preclinical study on rodents with CBZ
      HA and CBZ-FA has yielded appreciable results in terms of their anticonvulsant
      and antioxidants activities. However, CBZ-HA (1:2) demonstrated better result
      than any other complex. 

PMID- 25755979
TI  - Inclusion complex of a new propiconazole derivative with beta-cyclodextrin: NMR,
      ESI-MS and preliminary pharmacological studies.
AB  - A novel inclusion complex of the propiconazole nitrate (NO3PCZ) with beta
      cyclodextrin (beta-CD) was prepared by treatment of propiconazole (PCZ) with an
      acidic nitrating agent. The formation of NO3PCZ and its inclusion complex with
      beta-CD has been studied by NMR, ESI-MS, TGA, DSC methods. Using the undecoupled
      signal in the HMBC correlation spectra, almost identical coupling constants of CH
      from trizolic ring of PCZ and NO3PCZ compounds ((1)J(HC)3=207 Hz, (1)J(CH)5=214
      Hz, for PCZ; (1)J(HC)3=208 Hz and (1)J(CH)5=215 Hz, for NO3PCZ) were determined,
      confirming that the geometry of the heterocyclic skeleton is identical in both
      the forms. The 1:1 stoichiometry of the complex was determined by ESI-MS and was
      confirmed using Scott's equation in DMSO and Higuchi and Connors equation in
      water. The solubility curve obtained for NO3PCZ in presence of beta-CD in
      distilled water was constructed, resulting in a solubility diagram of AL type.
      Solubility of NO3PCZ in water was determined by DLS studies. The results showed
      that NO3PCZ was encapsulated within the beta-CD cavity with a binding constant of
      330 M-1 in DMSO and 975 M-1 in water. Preliminary pharmacological studies showed
      higher antifungal activities for NO3PCZ and its inclusion complex, compared with
      its PCZ analog. The acute toxicity of the complex is smaller than the pure or
      modified drug, recommending the inclusion complex as future promising therapeutic
      agents. 

PMID- 25755980
TI  - Interaction of artesunate with beta-cyclodextrin: Characterization, thermodynamic
      parameters, molecular modeling, effect of PEG on complexation and antimalarial
      activity.
AB  - Inclusion of artesunate in the cavity of beta-cyclodextrin (beta-CD) as well as
      its methyl and hydroxypropyl derivatives was investigated experimentally and by
      molecular modeling studies. The effect of PEG on the inclusion was also studied.
      A 1:1 stoichiometry was indicated by phase-solubility studies both in the
      presence and absence of PEG and suggested by the mass spectrometry. The mode of
      inclusion was supported by 2D NMR and results were further verified by docking
      studies utilizing Fast Rigid Exhaustive Docking acronym. The thermodynamic
      parameters were determined for both binary and ternary systems using solution
      calorimetry and were found to be best for the methyl-beta-cyclodextrin (Me-beta
      CD) system. However, the presence of PEG improves the complexation ability as
      evident from elevation in the numerical value of the stability constant (K).
      Solubility and dissolution profile of binary complex is enhanced in the presence
      of PEG, which is approximately at par with drug Me-beta-CD complexes. In vivo
      studies showed 100% survivability in artesunate-Me-beta-CD complexes. 

PMID- 25755981
TI  - A simple protocol for preparation of a liposomal vesicle with encapsulated
      plasmid DNA that mediate high accumulation and reporter gene activity in tumor
      tissue.
AB  - The systemic delivery of gene therapeutics by non-viral methods has proven
      difficult. Transfection systems that are performing well in vitro have been
      reported to have disadvantageous properties such as rapid clearance and short
      circulation time often resulting in poor transfection efficiency when applied in
      vivo. Large unilaminary vesicles (LUV) with encapsulated nucleic acids designated
      stabilized-plasmid-lipo-particle (SPLP) have showed promising results in terms of
      systemic stability and accumulation in tumor tissue due to the enhanced
      permeability and retention effect (EPR). We have developed a simple protocol for
      the research-scale preparation of SPLPs from commercially available reagents with
      high amounts of encapsulated plasmid DNA. The SPLPs show properties of promising
      accumulation in tumor tissue in comparison to other organs when intravenously
      injected into xenograft tumor-bearing nude mice. Although transcriptionally
      targeted suicide gene therapy was not achieved, the SPLPs were capable of
      mediating reporter gene transfection in subcutaneous flank tumors originating
      from human small cell lung cancer. 

PMID- 25755982
TI  - Oral bioavailability of a poorly aqueous drug from three different SBE7-beta
      cyclodextrin based formulations in beagle dogs.
AB  - Oral administration of Lu 35-138, a low aqueous soluble compound, was
      investigated in three different formulations containing sulfobutylether beta
      cyclodextrin (SBE7betaCD) in fasted beagle dogs. The evaluated formulations was
      (i) a SBE7betaCD solution, (ii) a spray dried solution filled into hard gelatine
      capsules, and (iii) a direct compressible tablet containing SBE7betaCD. The three
      formulations did not lead any significant differences in the obtained AUCs,
      though a trend was observed for the highest absorption when Lu 35-138 was dosed
      in the cyclodextrin solution. These results demonstrate that a solid formulation
      with a relative low content of cyclodextrins can be used to increase the
      bioavailability of a low water soluble compound to a relative high level when
      compared to a cyclodextrin solution. 

PMID- 25755983
TI  - Nanosized ethosomes bearing ketoprofen for improved transdermal delivery.
AB  - The potential of ethosomes for delivering ketoprofen via skin was evaluated. The
      ethosomes were prepared, optimized and characterized. Vesicular shape, size and
      entrapment efficiency were determined by transmission electron microscopy,
      dynamic light scattering and minicolumn centrifugation technique, respectively.
      Vesicle sizes varied from 120.3+/-6.1 to 410.2+/-21.8 nm depending on the
      concentrations of soya phosphatidyl choline (SPC) and ethanol. Entrapment
      efficiency increased with concentrations of SPC and ethanol. The formulations
      exhibited entrapment efficiencies of 42-78%. In vitro release through cellophane
      membrane showed sustained release of drug from ethosomal formulations in contrast
      to hydroalcoholic drug solution (HA), which released most of the drug within 2-3
      h. In vitro drug permeation across human skin revealed improved drug permeation
      and higher transdermal flux with ethosomal formulations compared to
      hydroethanolic drug solution. Kinetics of in vitro skin permeation showed zero
      order drug release from formulations. Based on in vitro transdermal flux, the
      estimated steady state in vivo plasma concentration from ethosomes attained
      therapeutic drug levels whereas hydroalcoholic drug solution exhibited sub
      therapeutic drug concentration with a patch size of 50 cm(2). Skin permeation of
      ethosomal formulations assessed by confocal microscopy revealed enhanced
      permeation of Rhodamine 123 loaded formulation in comparison to the
      hydroalcoholic solution. 

PMID- 25755984
TI  - Effects of doxorubicin-encapsulating AG73 peptide-modified liposomes on tumor
      selectivity and cytotoxicity.
AB  - Doxorubicin-encapsulating liposomal formulations, known as Doxil, have been used
      for the treatment of Kaposi's sarcoma and ovarian cancer. However, there is still
      a need for a drug delivery system for doxorubicin that limits the treatment's
      side effects, namely, mucositis and hand-and-foot syndrome. The AG73 peptide
      derived from the laminin alpha1 chain is a ligand for syndecans, and syndecan-2
      is highly expressed in some cancer cells. In this study, to develop a safer and
      more selective liposomal formulation, we prepared doxorubicin-encapsulating AG73
      peptide-modified liposomes (AG73-Dox). First, we assessed the selectivity of AG73
      Dox for cancer cells, including syndecan-2 over-expressing cells, using flow
      cytometry and confocal microscopy. AG73-Dox showed selective cellular uptake on
      cancer cells and enhancement of the intracellular uptake. Next, we examined the
      cytotoxicity of AG73-Dox using a WST assay. AG73-Dox exhibited a higher
      cytotoxicity against cancer cells than other control liposomes. In addition, we
      showed that the antitumor efficacy of AG73-Dox in vivo was better than that of
      free Dox. When we examined the biodistribution of liposomes, AG73 peptide
      modified liposomes (AG73-L) tended to bind to intratumoral vessels and
      extravasated in the tumor tissue. Thus, further optimization of AG73-L toward
      tumor targeting may lead to a development of a useful tool for cancer therapy. 

PMID- 25755985
TI  - A microdialysis study of topically applied diclofenac to healthy humans: Passive
      versus iontophoretic delivery.
AB  - Topical application of NSAIDs is an alternative route to systemic administration
      when a local anti-inflammatory effect of the underlying tissue is a treatment
      option. The aim of the present microdialysis study was to assess and compare
      plasma and tissue levels of diclofenac when topically applied with or without
      iontophoresis in healthy adults. Fourteen healthy adults (26+/-9.4 years) were
      randomized to diclofenac applied by iontophoresis, or by a gel, in a crossover
      design. Diclofenac concentrations were measured in plasma and in microdialysis
      perfusates from the underlying tissues. Iontophoretic application resulted in the
      highest plasma concentration of 3.4+/-0.5 ng/ml (SEM given) compared to 0.4 ng/ml
      (at the detection limit) with gel, whereas no differences were observed between
      tissue concentrations for the two application methods, both being very low, below
      or around the detection limit. Iontophoresis caused skin reactions in 25% of the
      participants. Iontophoresis of diclofenac as compared to traditional topical
      application was not superior in order to increase the NSAID concentration locally
      and appears to have a higher frequency of skin reactions. 

PMID- 25755986
TI  - The application of co-melt-extruded poly(epsilon-caprolactone) as a controlled
      release drug delivery device when combined with novel bioactive drug candidates:
      Membrane permeation and Hanson dissolution studies.
AB  - Eight bioactive drug compounds (abamectin, amoxicillin, dexamethasone,
      dexamethasone valerate, ketoprofen, melatonin, oestradiol 17beta, and oestradiol
      benzoate) were combined via melt extrusion and disc pressing processes with a
      polycaprolactone (PCL) matrix and were then evaluated and compared via membrane
      diffusion and Hanson dissolution studies. This investigation was to determine the
      potential of this matrix to act as a controlled release drug delivery vehicle for
      a number of drugs not previously combined with PCL in a melt extrusion mix. The
      inclusion of the progesterone/PCL system, for which the drug release behaviour
      has been well studied before was intended for comparison with the PCL systems
      incorporating drugs that have received little research attention in the past.
      Initial studies centred on an evaluation of the permeation ability of the
      bioactive drugs dissolved in aqueous cyclodextrin solutions through a
      poly(epsilon-caprolactone) (PCL) membrane using Valia-Chien side-by-side cells.
      Permeation rates were mostly low and found to range from 0 to 122 MUg h(-1) with
      only ketoprofen, melatonin, and progesterone displaying rates exceeding 20 MUg h(
      1). Hanson dissolution release profiles in aqueous alcohol were subsequently
      measured for the 9 melt extruded PCL/drug combinations and led to Hanson release
      rates of 0-556 MUg cm(-2) h(-0.5) with dexamethasone, dexamethasone valerate,
      ketoprofen, melatonin, and progesterone giving values exceeding 100 MUg cm(-2) h(
      0.5). A number of drugs such as the dexamethasones probably performed better than
      they did in the permeability rate measurements because of the less polar aqueous
      alcoholic solvent used. In searching for useful correlations between the drug
      physicochemical properties and release rate, only a moderate correlation (R
      (2)=0.5675) between Hanson dissolution release rate and permeation rate was
      found. This suggests that the release rate and the permeation are both controlled
      by the rate of drug diffusion through the PCL with release rate involving an
      additional dissolution process (of the drug) before permeation occurs accounting
      for the moderate correlation. In general, of the eight drugs considered, it was
      clear that the oestradiol-based drugs, abamectin, and amoxicillin were generally
      not suited to drug delivery via PCL under the conditions used. However,
      ketoprofen was found to be very suitable as a drug candidate for melt extrusion
      with PCL with dexamethasone valerate, dexamethasone, and melatonin also showing
      potential as candidates though to a much lesser extent. 

PMID- 25755987
TI  - Publisher note.

PMID- 25755988
TI  - The differences between the branded and generic medicines using solid dosage
      forms: In-vitro dissolution testing.
AB  - INTRODUCTION: Dissolution is the amount of substance that goes into solution per
      unit time under standardised conditions of liquid/solid interface, solvent
      composition and temperature. Dissolution is one of the most important tools to
      predict the in-vivo bioavailability and in some cases to determine bioequivalence
      and assure interchangeability. AIM: To compare the differences in dissolution
      behaviour of solid dosage forms between innovators (reference products) and their
      generic counterparts (tested products). METHODS: Four replicates for each batch
      of 37 tested medicines was carried out using A PT-DT70 dissolution tester from
      Pharma Test. A total of 13 branded medicines and 24 generic counterparts were
      obtained locally and internationally to detect any differences in their
      dissolution behaviour. They were tested according to the British Pharmacopeia,
      European Pharmacopeia and the US Pharmacopeia with the rate of dissolution
      determined by ultra-violet Spectrophotometery. RESULTS: Most tested medicines
      complied with the pharmacopoeial specifications and achieved 85% dissolution in
      60 min. However, some generic medicines showed significant differences in
      dissolution rate at 60 and 120 min. Many generic medicines showed a slower
      dissolution rate than their branded counterparts such as the generic forms of
      omeprazole 20 mg. Some showed an incomplete dissolution such as the generic form
      of nifedipine 10 mg. Other generics showed faster dissolution rate than their
      branded counterpart such as the generic forms of meloxicam 15 mg. Moreover, some
      generics from different batches of the same manufacturer showed significant
      differences in their dissolution rate such as the generic forms of meloxicam 7.5
      mg. Nevertheless, some generic medicines violated the EMA and the FDA guidelines
      for industry when they failed to achieve 85% dissolution at 60 min, such as the
      generic form of diclofenac sodium 50 mg. CONCLUSION: Most medicines in this study
      complied with the pharmacopeial limits. However, some generics dissolved
      differently than their branded counterparts. This can clearly question the
      interchangeability between the branded and its generic counterpart or even among
      generics.

PMID- 25755989
TI  - Anti-angiogenic poly-L-lysine dendrimer binds heparin and neutralizes its
      activity.
AB  - The interaction between heparin, a polyanion, and a polycationic dendrimer with a
      glycine core and lysine branches Gly-Lys63(NH2)64 has been investigated.
      Complexation was assessed by transmission electron microscopy, size and zeta
      potential measurements, methylene blue spectroscopy, and measuring the anti
      coagulant activity of heparin in vitro and in vivo. Complete association between
      the heparin and the dendrimer occurred a 1:1 mass ratio (2:1 molar ratio or +/
      charge ratio) with formation of quasi-spherical complexes in the size range of 99
      147 nm with a negative zeta potential (-47 mV). Heparin-dendrimer (dendriplex)
      formation led to a concentration-dependent neutralization of the anticoagulant
      activity of heparin in human plasma in vitro, with complete loss of activity at a
      1:1 mass ratio. The anticoagulant activity of the dendriplexes in Sprague-Dawley
      rats was also evaluated after subcutaneous administration with uncomplexed
      heparin as a comparator. The in vivo anticoagulant activity of heparin in plasma,
      evaluated using an antifactor Xa assay, was abolished after complexation.
      Measurement of [(3)H]-heparin showed that both free heparin and dendriplexes were
      present in plasma and in organs. Such data confirmed stably the formation of
      dendriplexes, which could be essential in developing novel dendrimer-based anti
      angiogenic therapeutics suitable in combinatory therapeutics and theranostics. 

PMID- 25755990
TI  - Oil-in-water emulsion lotion providing controlled release using 2
      methacryloyloxyethyl phosphorylcholine n-butyl methacrylate copolymer as
      emulsifier.
AB  - Lotion is a useful vehicle for active ingredients used to treat skin disease
      because it can be applied to the scalp, can cover large areas of skin, and it is
      easy to spread due to low viscosity. An emulsion lotion (EL) containing 2
      methacryloyloxyethyl phosphorylcholine n-butyl methacrylate copolymer (PMB) as an
      emulsifier that provides controlled-release was developed. Diphenhydramine (DPH)
      was used as a model drug. Formulation with 5% DPH, 5% soybean oil, and 4% PMB in
      water was emulsified using a high-pressure homogenizer. Polysorbate 80 (TO) was
      used instead of PMB for comparison. They were applied in vitro to Yucatan
      micropig intact or stripped skin at a practical dose (2 MUL/cm(2)). For stripped
      skin, penetration of DPH from 4% PMB EL was slower than that from 1% TO EL;
      results for intact skin were similar. The same phenomenon was observed with
      application to rabbit skin in vivo. When 4% PMB EL dried on the skin, it made a
      thin film matrix incorporating the oil phase, which controlled the release of
      DPH. The release rate could be controlled by the ratio of oil phase to PMB. The
      EL with PMB shows promise as a vehicle for long-acting treatment of skin
      diseases. 

PMID- 25755991
TI  - Polymer excipients enable sustained drug release in low pH from mechanically
      strong inorganic geopolymers.
AB  - Improving acid resistance, while maintaining the excellent mechanical stability
      is crucial in the development of a sustained and safe oral geopolymer dosage form
      for highly potent opioids. In the present work, commercially available
      Methacrylic acid-ethyl acrylate copolymer, Polyethylene-glycol (PEG) and Alginate
      polymer excipients were included in dissolved or powder form in geopolymer
      pellets to improve the release properties of Zolpidem, herein acting as a model
      drug for the highly potent opioid Fentanyl. Scanning electron microscopy,
      compression strength tests and drug release experiments, in gastric pH 1 and
      intestinal pH 6.8 conditions, were performed. The polymer excipients, with an
      exception for PEG, reduced the drug release rate in pH 1 due to their ability to
      keep the pellets in shape, in combination with the introduction of an insoluble
      excipient, and thereby maintain a barrier towards drug diffusion and release.
      Neither geopolymer compression strength nor the release in pH 6.8 was
      considerably impaired by the incorporation of the polymer excipients. The
      geopolymer/polymer composites combine high mechanical strength and good release
      properties under both gastric and intestinal pH conditions, and are therefore
      promising oral dosage forms for sustained release of highly potent opioids. 

PMID- 25755992
TI  - Applying terahertz technology for nondestructive detection of crack initiation in
      a film-coated layer on a swelling tablet.
AB  - Here, we describe a nondestructive approach using terahertz wave to detect crack
      initiation in a film-coated layer on a drug tablet. During scale-up and scale
      down of the film coating process, differences in film density and gaps between
      the film-coated layer and the uncoated tablet were generated due to differences
      in film coating process parameters, such as the tablet-filling rate in the
      coating machine, spray pressure, and gas-liquid ratio etc. Tablets using the
      PEO/PEG formulation were employed as uncoated tablets. We found that heat and
      humidity caused tablets to swell, thereby breaking the film-coated layer. Using
      our novel approach with terahertz wave nondestructively detect film surface
      density (FSD) and interface density differences (IDDs) between the film-coated
      layer and an uncoated tablet. We also found that a reduced FSD and IDD between
      the film-coated layer and uncoated tablet increased the risk of crack initiation
      in the film-coated layer, thereby enabling us to nondestructively predict
      initiation of cracks in the film-coated layer. Using this method, crack
      initiation can be nondestructively assessed in swelling tablets after the film
      coating process without conducting accelerated stability tests, and film coating
      process parameters during scale-up and scale-down studies can be appropriately
      established. 

PMID- 25755994
TI  - Release behavior of trans,trans-farnesol entrapped in amorphous silica capsules.
AB  - Farnesol, a compound widely found in several agro-food by-products, is an
      important bioactive agent that can be exploited in cosmetics and pharmaceutics
      but the direct bioapplication of this compound is limited by its volatility. Here
      the entrapment of farnesol in silica capsules was investigated to control the
      release of this bioactive compound in the vapor phase and in ethanol solutions.
      The preparation of silica capsules with oil cores was obtained by employing a sol
      gel method using O/W/O multiple emulsions. Two distinct chemical vehicles for
      farnesol have been investigated, retinol and oleic acid, that afterwards have
      been emulsified as internal oil phases. The volatile release of farnesol from the
      as-prepared SiO2 capsules was investigated by headspace solid phase
      microextraction (HS-SPME) followed by gas chromatographic analysis (GC), and the
      release to ethanol was carried out by direct injection of the ethanolic fraction
      into the GC system. It is demonstrated that these capsules are efficient for the
      long controlled release of farnesol and that the respective profiles depend on
      the chemical parameters employed in the synthesis of the capsules. 

PMID- 25755993
TI  - Development of oxaliplatin encapsulated in magnetic nanocarriers of pectin as a
      potential targeted drug delivery for cancer therapy.
AB  - Superparamagnetic iron oxide nanoparticles (SPIONs) and oxaliplatin (OHP) were in
      situ encapsulated in pectin cross-linked with Ca(2+) forming 100-200 nm sized
      magnetically functionalized pectin nanocarriers, referred here as MP-OHP
      nanocarriers. The scanning electron microscopy (SEM) and transmission electron
      microscopy (TEM) studies revealed formation of spherical nanostructures. The
      magnetic measurements by vibration sample magnetometer (VSM) revealed high
      saturation magnetization (M s=45.65 emu/g). The superparamagnetic property of MP
      OHP was confirmed from the blocking temperature (T B) determined from field
      cooled and zero field cooled magnetization, measured by superconducting quantum
      unit interference device (SQUID) magnetometry. The stability of the aqueous
      dispersion of MP-OHP nanocarriers was confirmed from its high zeta potential (
      30.5 mV). The drug encapsulation efficiency (55.2+/-4.8% w/w) and the drug
      loading content (0.10+/-0.04 wt%) in MP-OHP nanocarriers were determined from
      corresponding platinum contents in OHP and MP-OHP batches measured by inductively
      coupled plasma mass spectrometry (ICPMS). These nanocarriers exhibited a
      sustained release of OHP in phosphate buffer solution maintained at pH 5.5 and
      7.4, where the drug release profile satisfied a combination of diffusion and
      swelling controlled mechanism. The cytotoxicity effect of MP-OHP nanocarriers was
      studied on MIA-PaCa-2 (pancreas) cancer cell line, where the GI50 values were
      more than 5 mg/mL and it exhibited 10 folds higher cytoxicity than the equivalent
      concentration of free drug. 

PMID- 25755995
TI  - Enzymatic mono-pegylation of glucagon-like peptide 1 towards long lasting
      treatment of type 2 diabetes.
AB  - Human glucagon-like peptide-1 (GLP-1) is a physiological gastrointestinal peptide
      with glucose-dependent insulinotropic effects which is therefore considered an
      interesting antidiabetic agent. However, after in vivo administration, exogenous
      GLP-1 does not exert its physiological action due to the combination of rapid
      proteolytic degradation by ubiquitous dipeptidyldipeptidase IV (DPP IV) enzyme
      and renal clearance resulting in an extremely short circulating half-life. In
      this work we describe the conjugation of GLP-1-(7-36)-amide derivatives with
      polyethylene glycol (PEG) by enzymatic site-specific transglutamination reaction
      as an approach to reduce both the proteolysis and the renal clearance rates. The
      compound GLP-1-(7-36)-amide-Q(23)-PEG 20 kDa monopegylated on the single
      glutamine residue naturally present in position 23 maintained the ability to
      activate the GLP-1 receptor expressed in the rat beta-cell line RIN-m5F with
      nanomolar potency along with an increased in vitro resistance to DDP IV and a
      circulating half-life of about 12 h after subcutaneous administration in rats.
      These properties enabled GLP-(7-36)-amide-Q(23)-PEG 20 kDa to exert a glucose
      stabilizing effect for a period as long as 8 h, as demonstrated by a single
      subcutaneous injection to diabetic mice concomitantly challenged with an oral
      glucose load. The results reported in this work indicate that GLP-(7-36)-amide
      Q(23)-PEG 20 kDa could be a lead compound for the development of long-lasting
      anti-diabetic agents useful in the treatment of type 2 diabetes affected
      patients. 

PMID- 25755996
TI  - Moxifloxacin in situ gelling microparticles-bioadhesive delivery system.
AB  - Antibiotic use for ocular treatments has been largely limited by poor local
      bioavailability with conventional eyedrops formulations. Here, we developed a
      controlled delivery system composed of moxifloxacin-loaded poly(lactic-co
      glycolic acid) (PLGA) microparticles encapsulated in a chondroitin sulfate-based,
      two-component bioadhesive hydrogel. Using a simple and fast electrohydrodynamic
      spray drying (electrospraying) technique, surfactant-free moxifloxacin-loaded
      microparticles were fabricated with diameters on the order of 1 MUm. A mixed
      solvent system of methanol/dichloromethane (MeOH/DCM) was employed to prepare the
      microparticles for the electrospraying processing. Extended release of
      moxifloxacin using a series of MeOH/DCM mixed solvents was accomplished over 10
      days with release concentrations higher than the minimum inhibitory concentration
      (MIC). In contrast, moxifloxacin loaded directly in hydrogels was released
      rapidly within 24 h. We observed a decrease of the drug release rate from the
      microparticles when using an increased percentage of methanol in the mixed
      solvent from 10% to 30% (v/v), which can be explained by the mixed solvent system
      providing a driving force to form a gradient of the drug concentrations inside
      the microparticles. In addition, the delivery system developed in this study,
      which incorporates a bioadhesive to localize drug release by in situ gelling, may
      potentially integrate antibiotic prophylaxis and wound healing in the eye. 

PMID- 25755997
TI  - Regenerated keratin membrane to match the in vitro drug diffusion through human
      epidermis.
AB  - This work aimed to develop membranes made of regenerated keratin and ceramides
      (CERs) to match the barrier property of the human stratum corneum in in vitro
      percutaneous absorption studies. The membrane composition was optimized on the
      basis of the in vitro drug diffusion profiles of ibuprofen, propranolol and
      testosterone chosen as model drugs on the basis of their different diffusion and
      solubility properties. The data were compared to those obtained using human
      epidermis. The ATR-FTIR and SEM analyses revealed that CERs were suspended into
      the regenerated keratin matrix, even if a partial solubilization occurred. It
      resulted in the membranes being physically stable after exposure to aqueous
      buffer and/or mineral oil and the fluxes of ibuprofen and propranolol from these
      vehicles through membranes and human skin were of the same order of magnitude.
      The best relationship with human epidermis data was obtained with 180 MUm-thick
      membrane containing 1% ceramide III and 1% ceramide VI. The data on the
      testosterone diffusion were affected by the exposure of the membrane to a
      water/ethanol solution over a prolonged period of time, indicating that such an
      organic solvent was able to modify the supermolecular organization of keratin and
      CERs. The keratin/CER membranes can represent a simplified model to assay the in
      vitro skin permeability study of small molecules. 

PMID- 25755998
TI  - Capsule shell material impacts the in vitro disintegration and dissolution
      behaviour of a green tea extract.
AB  - PURPOSE: In vitro disintegration and dissolution are routine methods used to
      assess the performance and quality of oral dosage forms. The purpose of the
      current work was to determine the potential for interaction between capsule shell
      material and a green tea extract and the impact it can have on the release.
      METHODS: A green tea extract was formulated into simple powder-in-capsule
      formulations of which the capsule shell material was either of gelatin or HPMC
      origin. The disintegration times were determined together with the dissolution
      profiles in compendial and biorelevant media. RESULTS: All formulations
      disintegrated within 30 min, meeting the USP criteria for botanical formulations.
      An immediate release dissolution profile was achieved for gelatin capsules in all
      media but not for the specified HPMC formulations. Dissolution release was
      especially impaired for HPMCgell at pH 1.2 and for both HPMC formulations in
      FeSSIF media suggesting the potential for food interactions. CONCLUSIONS: The
      delayed release from studied HPMC capsule materials is likely attributed to an
      interaction between the catechins, the major constituents of the green tea
      extract, and the capsule shell material. An assessment of in vitro dissolution is
      recommended prior to the release of a dietary supplement or clinical trial
      investigational product to ensure efficacy.

PMID- 25756000
TI  - Relationship between the usability and physicochemical properties of
      triamcinolone acetonide ointments.
AB  - The purpose of this study was to examine the physicochemical properties of TA
      ointments and conduct a human sensory test to assess the properties of those
      ointments. Physicochemical assessment was done via near-infrared (NIR) absorption
      spectroscopy, measurement of water content, microscopy, and measurement of
      viscoelasticity. The human sensory test examined 5 aspects (texture,
      cohesiveness, spreadability, smell, and feel). Three TA ointments were used: TA
      A, a brand-name preparation, and TA-B and TA-C, two generics. The sensory test
      revealed significant differences between TA-A and TA-B and TA-C in terms of
      cohesiveness and spreadability. Significant differences between TA-A and TA-C and
      between TA-B and TA-C in terms of feel were noted. Microscopic examination
      revealed that TA-C had good dispersibility while TA-A and TA-B produced
      crystallization. NIR spectroscopy revealed differences in absorption spectra
      attributed to oil and water content in TAA, TA-B, and TA-C. Measurement of water
      content indicated water content of 0.06 +/- 0.02% for TA-A, 0.08 +/- 0.08% for TA
      B, and 36.7 +/- 1.19% for TA-C. Assessment of viscoelasticity indicated that
      stress decreased for all 3 ointments at 35  degrees C compared to that at 25 
      degrees C. TA-A and TA-B were found to have a higher percent decrease in stress
      than was TA-C. These findings indicate that differences in the types and content
      of additives caused differences in the physicochemical properties of individual
      ointments. In addition, differences in physicochemical properties presumably
      resulted in the close correlation between cohesiveness and spreadability in the
      sensory test. 

PMID- 25755999
TI  - Surfactants modify the release from tablets made of hydrophobically modified poly
      (acrylic acid).
AB  - Many novel pharmaceutically active substances are characterized by a high
      hydrophobicity and a low water solubility, which present challenges for their
      delivery as drugs. Tablets made from cross-linked hydrophobically modified poly
      (acrylic acid) (CLHMPAA), commercially available as PemulenTM, have previously
      shown promising abilities to control the release of hydrophobic model substances.
      This study further investigates the possibility to use CLHMPAA in tablet
      formulations using ibuprofen as a model substance. Furthermore, surfactants were
      added to the dissolution medium in order to simulate the presence of bile salts
      in the intestine. The release of ibuprofen is strongly affected by the presence
      of surfactant and/or buffer in the dissolution medium, which affect both the
      behaviour of CLHMPAA and the swelling of the gel layer that surrounds the
      disintegrating tablets. Two mechanisms of tablet disintegration were observed
      under shear, namely conventional dissolution of a soluble tablet matrix and
      erosion of swollen insoluble gel particles from the tablet. The effects of
      surfactant in the surrounding medium can be circumvented by addition of
      surfactant to the tablet. With added surfactant, tablets that may be
      insusceptible to the differences in bile salt level between fasted or fed states
      have been produced, thus addressing a central problem in controlled delivery of
      hydrophobic drugs. In other words CLHMPAA is a potential candidate to be used in
      tablet formulations for controlled release with poorly soluble drugs. 

PMID- 25756001
TI  - In vivo siRNA delivery system for targeting to the liver by poly-l-glutamic acid
      coated lipoplex.
AB  - In this study, we developed anionic polymer-coated liposome/siRNA complexes
      (lipoplexes) with chondroitin sulfate C (CS), poly-l-glutamic acid (PGA) and poly
      aspartic acid (PAA) for siRNA delivery by intravenous injection, and evaluated
      the biodistribution and gene silencing effect in mice. The sizes of CS-, PGA- and
      PAA-coated lipoplexes were about 200?nm and their ?-potentials were negative. CS
      , PGA- and PAA-coated lipoplexes did not induce agglutination after mixing with
      erythrocytes. In terms of biodistribution, siRNAs after intravenous
      administration of cationic lipoplexes were largely observed in the lungs, but
      those of CS-, PGA- and PAA-coated lipoplexes were in both the liver and the
      kidneys, indicating that siRNA might be partially released from the anionic
      polymer-coated lipoplexes in the blood circulation and accumulate in the kidney,
      although the lipoplexes can prevent the agglutination with blood components. To
      increase the association between siRNA and cationic liposome, we used cholesterol
      modified siRNA (siRNA-Chol) for preparation of the lipoplexes. When CS-, PGA- and
      PAA-coated lipoplexes of siRNA-Chol were injected into mice, siRNA-Chol was
      mainly observed in the liver, not in the kidneys. In terms of the suppression of
      gene expression in vivo, apolipoprotein B (ApoB) mRNA in the liver was
      significantly reduced 48?h after single intravenous injection of PGA-coated
      lipoplex of ApoB siRNA-Chol (2.5?mg?siRNA/kg), but not cationic, CS- and PAA
      coated lipoplexes. In terms of toxicity after intravenous injection, CS-, PGA-
      and PAA-coated lipoplexes did not increase GOT and GPT concentrations in blood.
      From these findings, PGA coatings for cationic lipoplex of siRNA-Chol might
      produce a systemic vector of siRNA to the liver. 

PMID- 25756002
TI  - Safety of poly (ethylene glycol)-coated perfluorodecalin-filled poly (lactide-co
      glycolide) microcapsules following intravenous administration of high amounts in
      rats.
AB  - The host response against foreign materials designates the biocompatibility of
      intravenously administered microcapsules and thus, widely affects their potential
      for subsequent clinical use as artificial oxygen/drug carriers. Therefore, body
      distribution and systemic parameters, as well as markers of inflammation and
      indicators of organ damage were carefully evaluated after administration of short
      chained poly (vinyl alcohol, (PVA)) solution or poly (ethylene glycol (PEG))
      shielded perfluorodecalin-filled poly (d,l-lactide-co-glycolide, PFD-filled PLGA)
      microcapsules into Wistar rats. Whereas PVA infusion was well tolerated, all
      animals survived the selected dose of 1247 mg microcapsules/kg body weight but
      showed marked toxicity (increased enzyme activities, rising pro-inflammatory
      cytokines and complement factors) and developed a mild metabolic acidosis. The
      observed hypotension emerging immediately after start of capsule infusion was
      transient and mean arterial blood pressure restored to baseline within 70 min.
      Microcapsules accumulated in spleen and liver (but not in other organs) and
      partly occluded hepatic microcirculation reducing sinusoidal perfusion rate by
      about 20%. Intravenous infusion of high amounts of PFD-filled PLGA microcapsules
      was tolerated temporarily but associated with severe side effects such as
      hypotension and organ damage. Short-chained PVA displays excellent
      biocompatibility and thus, can be utilized as emulsifier for the preparation of
      drug carriers designed for intravenous use. 

PMID- 25756003
TI  - Biological conversion of aripiprazole lauroxil - An N-acyloxymethyl aripiprazole
      prodrug.
AB  - N-acyloxyalkylation of NH-acidic compounds can be a prodrug approach for e.g.
      tertiary or some N-heterocyclic amines and secondary amides and have the
      potential to modify the properties of the parent drug for specific uses, for
      example its physicochemical, pharmacokinetic or biopharmaceutical properties.
      Aripiprazole lauroxil was prepared as a model compound for such prodrugs and its
      bioconversion was investigated both in vitro and in vivo. Theoretically, N
      acyloxyalkyl derivates of NH-acid compounds undergo a two-step bioconversion into
      the parent NH-acidic drug through an N-hydroxyalkyl intermediate. However, to our
      knowledge no published studies have investigated the formation of an intermediate
      in vivo. In the present study, it was demonstrated that the assumed N
      hydroxymethyl intermediate was readily observed both in vitro and in vivo. In
      vivo, the observed plasma concentration of the intermediate was at the same level
      as the drug (aripiprazole). When prodrug intermediates are formed, it is
      important to make a proper pharmacological, pharmacokinetic and toxicological
      evaluation of the intermediates to ensure patient safety; however, several
      challenges were identified when testing an N-acyloxyalkyl prodrug. These included
      the development of a suitable bioanalytical method, the accurate prediction of
      prodrug bioconversion and thereby the related pharmacokinetics in humans and the
      toxicological potential of the intermediate. 

PMID- 25756004
TI  - Development and validation of an alternative disturbed skin model by mechanical
      abrasion to study drug penetration.
AB  - Pharmaceuticals and cosmetics for dermal application are usually tested on
      healthy skin, although the primary permeation barrier, the stratum corneum, is
      often impaired by skin diseases or small skin lesions, especially on the hands.
      These skin conditions can considerably influence the permeation of chemicals and
      drugs. Furthermore, risk assessment for example of nanoparticles should be
      performed under various skin conditions to reflect the true circumstances.
      Therefore, an alternative and reproducible method for a high throughput of skin
      samples with impaired skin barrier was developed and verified by skin permeation
      studies (25 h) of caffeine, sorbic acid and testosterone compared to healthy
      (untreated) and tape-stripped skin. Skin barrier disruption was controlled by
      TEWL measurement. Skin permeation of the three substances was increased in tape
      stripped and abraded skin compared to untreated skin due to the reduced barrier
      integrity. Enhancement of drug uptake was highest for the most hydrophilic
      substance, caffeine, followed by sorbic acid and lipophilic testosterone. No
      significant difference in drug uptake studies was observed between the new
      abrasion method with an aluminum-coated sponge and the tape-stripping method. The
      obtained results demonstrate that this abrasion method is an alternative way to
      achieve a disturbed skin barrier for drug and chemical uptake studies. 

PMID- 25756005
TI  - Effect of the excipient concentration on the pharmacokinetics of PM181104, a
      novel antimicrobial thiazolyl cyclic peptide antibiotic, following intravenous
      administration to mice.
AB  - Thiazolyl cyclic peptide antibiotics are known for their poor aqueous solubility
      and unfavorable pharmacokinetics (PK) and hence pose challenging tasks in
      developing these antibiotics as clinical candidates. In the current paper, we
      report a possible way to address these challenges with exemplification of our
      antibiotic PM181104. The approach was to prepare formulations with known
      excipients, Polysorbate 80 (Tween 80, T-80) and PEG 400 through their varied
      stiochiometric combination in appropriate ratio to achieve acceptable osmolarity,
      pH and particle size of the formulation. Two different sets of formulations were
      prepared with two distinct average particle diameters ranging from 32.8 to 465.4
      nm. First, semi-transparent solutions with a particle size of >100 nm were
      achieved by keeping concentration of PEG 400 constant at 8% (w/v) and decreasing
      the amounts of T-80. Second, clear colorless solutions with a particle size of
      <100 nm were achieved by keeping concentration of T-80 constant at 8% (w/v) and
      decreasing the amounts of PEG 400. In PK studies, intravenous administration of
      formulation with particle size <100 nm to mice resulted in a two-fold increase in
      area under the plasma concentration-time curve (AUClast) and concentration at
      time zero (C 0), there by facilitating the selection of suitable formulation for
      further efficacy studies. 

PMID- 25756006
TI  - Evaluation of formulation properties and skin penetration in the same additive
      containing formulation.
AB  - The aim of this study is to examine the physicochemical properties of the
      external preparation, the effect on the skin permeability and the human senses.
      Miconazole nitrate cream formulation (MCZ-A: bland name and MCZ-B, -C, -D:
      generics) to measure the physicochemical properties, was performed by the skin
      permeation test and human sensory test. The flattening, viscoelasticity, and
      water content of each cream were measured and each cream was subjected to near
      infrared (NIR) absorption spectroscopy and human sensory testing. The yield value
      was calculated based on measured flattening and was 734.8 dynes/cm(2) for MCZ-A,
      1198.9 dynes/cm(2) for MCZ-B, 461.3 dynes/cm(2) for MCZ-C and 3112.3 dynes/cm(2)
      for MCZ-D. Measurement of viscoelasticity and viscosity revealed that MCZ-C had a
      smaller tandelta than the other 3 creams at 25  degrees C. NIR absorption
      spectroscopy revealed that MCZ-A had the highest absorption peak due to hydroxyl
      groups, followed by MCZ-C, -B, and then -D. Measurement of water content revealed
      that MCZ-A had a water content of 65.9%, MCZ-B, -C, and -D had a water content of
      around 56.3%. Human sensory testing revealed differences between MCZ-A and MCZ-C
      and between MCZ-B and MCZ-D in terms of spreadability and feel. These findings
      indicate that differences in water and oil content and emulsification resulted in
      the creams having different physical properties, such as flattening, internal
      structure, and dynamic viscoelasticity. NIR absorption spectroscopy, which allows
      non-destructive measurement of a sample's physicochemical properties, and
      measurement of viscoelasticity and viscosity, which allows measurement of a
      sample's dynamic viscoelasticity, revealed differences in the physical properties
      of creams. The skin permeation test, skin MCZ amount was 7.48 ug/cm(2) for MCZ-A,
      5.11 ug/cm(2) for MCZ-B, 12.08 ug/cm(2) for MCZ-C and 3.75 ug/cm(2) for MCZ-D. In
      addition, since the drug spread is good about the skin migration, spreadability
      is affecting the potential dermal transfer. 

PMID- 25756008
TI  - Signs of the times.

PMID- 25756007
TI  - Schizophyllum commune-induced allergic fungal rhinosinusitis and sinobronchial
      mycosis.
AB  - We present 32- and 38-year-old males with Schizophyllum commune-induced allergic
      fungal rhinosinusitis (AFRS). S. commune-induced AFRS was diagnosed by clinical
      and radiographic findings, positive specific IgE antibodies against S. commune as
      measured by the ImmunoCAP system, and sequencing analysis of the fungus. Our two
      cases with S. commune-induced AFRS for the first time showed evidence for type 1
      hypersensitivity to S. commune as determined by using specific IgE antibodies
      against S. commune, and the fungus was identified by sequence analysis. 

PMID- 25756009
TI  - A new beginning to oral and maxillofacial surgery.

PMID- 25756010
TI  - Analysis for speech and esthetics in sixty consecutive patients with cleft lip
      and palate.
AB  - BACKGROUND: A double-blind retrospective study was carried out at our oral and
      maxillofacial surgery department to assess speech and esthetics of primary
      cheiloplasty in patients operated for unilateral complete cleft lip, alveolus and
      palate. MATERIALS AND METHODS: Total sample size was 60. All were operated for
      unilateral complete cleft lip, alveolus and palate. Age range was between 1 and
      21 years. Results of surgeries performed by two surgeons were assessed. The
      speech of all these patients was judged by a single speech therapist who was
      unaware of the operating surgeon. All patients were assessed for articulatory
      errors, namely, omission, distortion, substitution, addition and intelligibility.
      Sixty-eight words in local language (Kannada) were selected by the speech
      pathologist. All patients were subdivided into three age groups: <=5 years, 6-10
      years and >=11 years. The cheiloplasty was assessed using VLS (V: vermilion, L:
      lip, S: scar) scale for vermilion, lip and scar patterns. RESULTS AND CONCLUSION:
      Patients undergoing palatoplasty in <=1 year showed good articulation between the
      age of 5 and 10 years. Articulation and intelligibility was maximum in patients
      >=11 years. Patients at this age try various compensatory mechanisms to overcome
      communication disabilities. Based on the VLS scale, scarring was the least in all
      patients. Vermilion and lip patterns showed satisfactory results in most of the
      patients.

PMID- 25756011
TI  - Dimensional differences in mandibular antegonial notches in temporomandibular
      joint ankylosis.
AB  - BACKGROUND: Deep antegonial notch (AN) is seen in congenital and acquired
      abnormalities of mandible like condylar hypoplasia, temporomandibular joint
      ankylosis (TMA), muscular hypoactivity and brachial arch syndrome. This study was
      planned with an aim to study the depth of AN in TMA and find its relation with
      the duration of ankylosis. MATERIALS AND METHODS: The study comprised 20 cases of
      unilateral or bilateral TMA, with age range 8-25 years. A comparison between
      ipsilateral and contralateral AN was done on orthopantomograms of these bilateral
      and unilateral cases with the time period of total duration of ankylosis.
      RESULTS: Seven cases had right-sided ankylosis, six had left and seven had
      bilateral TMA where the history of ankylosis ranged from 6 months to 12 years.
      Spearman's rank correlation indicated a strong correlation between the duration
      of history of ankylosis and AN on the ipsilateral/contralateral sides. Wilcoxin
      signed rank test proved the results to be statistically significant. CONCLUSION:
      Deep accentuated AN is one of the clinical features of the TMA and has a direct
      relation to the morphology and growth pattern of mandible.

PMID- 25756012
TI  - A study of morphological patterns of lip prints in relation to gender of North
      Indian population.
AB  - BACKGROUND: Establishing a person's identity is a very important process in civil
      and criminal cases. Dental, fingerprint and DNA comparisons are probably the most
      common techniques allowing fast and secure identification processes. However, in
      certain circumstances related to the scene of the crime or due to lack of
      experienced personnel, these techniques might be unavailable; so there is still
      an increasing need for reliable alternative methods of establishing identity.
      OBJECTIVE: The objective of the study was to check for any peculiar lip patterns
      in relation to the sex of the individual and determine the most common lip
      patterns in the given population. MATERIALS AND METHODS: This study was conducted
      on 150 subjects, which included 75 males and 75 females, in the age group of 18
      30 years. After applying lipstick evenly, the lip print of each subject was
      obtained on a simple bond paper by a researcher, and later the lip print was then
      analyzed and interpreted. RESULTS: The intersected type was most commonly seen in
      females and branched in males. Reticular pattern was the least common type in
      both males and females. CONCLUSION: This study shows that the lip prints are
      unique to an individual and behold the potential for recognition of the sex of an
      individual.

PMID- 25756013
TI  - Role of platelet-rich plasma in combination with alloplastic bone substitute in
      regeneration of osseous defects.
AB  - INTRODUCTION: Bone grafts are frequently used for the treatment of bone defects,
      but can cause postoperative complications, and sometimes a sufficient quantity of
      bone is not available. Hence, synthetic biomaterials have been used as an
      alternative to autogenous bone grafts. Recent clinical reports suggest that
      application of autologous blood plasma enriched with platelets can enhance the
      formation of new bone. There are very few in vitro or in vivo studies published
      on the efficiency of platelet-rich plasma (PRP). The objective of this study was
      to evaluate the alloplastic bone substitute for its osteogenic potential with or
      without PRP. MATERIALS AND METHODS: Twenty-three patients with periapical bony
      defects were selected for this study. Clinical parameters such as pain visual
      analog scale (VAS), swelling, infection, graft migration, rejection,
      radiographical interpretations at regular interval and scintigraphic evaluation
      were done to evaluate osteogenic potential of alloplastic bone substitute with or
      without PRP. RESULTS: The highest acceleration in bone formation was observed in
      groups where alloplastic bone substitute was used with PRP. There were no
      statistically significant differences between the two groups regarding other
      outcome variables throughout the postoperative period. CONCLUSION: Addition of
      PRP significantly accelerates vascularization of the graft, improves soft tissue
      healing, reduces postoperative morbidity and enhances bone regeneration.

PMID- 25756014
TI  - Tobacco use in Northern India-Part 1: The detailed habit.
AB  - BACKGROUND: The finite details of tobacco consumption practices in north Indian
      population are hitherto not well described. This study depicts the modes of
      tobacco use, their relative frequency, demographic and psychosocial determinants.
      MATERIALS AND METHODS: Random stratified sampling from the list of blocks,
      villages and urban localities was done. The study was community-based house-to
      house survey using interview schedule. RESULTS: There were 1607 tobacco users:
      1399 male and 208 female; 1195 urban and 412 rural. Single mode of tobacco use
      was reported by 769 (47.85%). Chewing tobacco was prevalent in 511 (31.80%),
      smoking in 258 (16.55%) subjects and majority 838 (52.15%) had consistent
      multiple habit of smoking and chewing. Of the 10 preparations of tobacco use, the
      'top 5' ranked as tobacco-betel, gutka, cigarette, bidi and khaini. Gutka
      consumption was significantly higher between age group of 25 years and 55 years
      (chi(2) = 17.2; P<0.000). Majority of users, 576 (35.84%), started tobacco before
      25 years of age and about a fifth, 439 (27.32%) before 18 years. Men
      significantly used tobacco more than women (chi(2) = 73.2; P<0.000). Women
      (chi(2) = 73.2; P<0.000) preferred smokeless tobacco and perceived social barrier
      for smoking. CONCLUSION: Multiple or overlapping tobacco practices and other
      substances abuse were documented in Lucknow, the capital city of the most
      populous state Uttar Pradesh where chewing tobacco was the commonest as opposed
      to smoking.

PMID- 25756015
TI  - Considerations for single tooth replacement in an esthetic zone-review of
      conservative treatment options.
AB  - BACKGROUND: This literature review aimed to identify and assess the conservative
      treatment options for replacing a single missing anterior tooth, for patients who
      cannot afford implants or traditional bridges. MATERIALS AND METHODS: The
      evidence was obtained using MEDLINE searches. A total of 19 studies met the
      inclusion criteria. None of these studies scored higher than 10 of 17, suggesting
      that all studies did not have strong evidence. Three of the studies examined
      resin-bonded bridges (RBBs), whereas the other three investigated removable
      partial dentures (RPDs). None of the studies had random patient selection. Three
      of these studies had controlled allocation of patients. The other three allowed
      new patients to enter the study throughout the study period. Placement of the
      prosthesis was only conducted in one study, whereas the rest of the studies
      examined patients with preexisting prostheses. RESULTS AND CONCLUSION: In
      general, all 19 studies were weak due to poor study design, no acceptable
      controls, no direct comparison between RBBs and RPDs, lack of longitudinal
      studies and no differentiation between the anterior and posterior prostheses.
      Therefore, no definitive treatment conclusion can be made until studies of
      stronger design are conducted.

PMID- 25756016
TI  - Clinical spectrum of Treacher Collins syndrome.
AB  - Treacher Collins syndrome (TCS) is the most common of the human mandibulofacial
      dysostosis disorders. It is an autosomal-dominant disorder of the craniofacial
      development occurring between the fifth and the eighth weeks of embryonic
      development with an incidence of 1/50,000 live births, range between 1-40,000 and
      1-70,000. We present here the various clinical, radiographical and other
      diagnostic findings of the TCS to correlate the clinical assessment with the
      diagnostic imaging and review the various investigations and management options
      being carried out to improve their facial deformity. 

PMID- 25756017
TI  - Periodontal regeneration in deep intrabony periodontal defect using
      hydroxyapatite particles with platelet rich fibrin membrane-a case report.
AB  - BACKGROUND: Growth factors such as platelet-derived growth factors exert potent
      effect on wound healing including the regeneration of periodontium. Platelet-rich
      fibrin (PRF) membrane provides a concentrate of such growth factors, accelerating
      the wound healing process. MATERIALS AND METHODS: In this case report,
      regeneration of the deep periodontal intrabony defect was attempted using
      hydroxyapatite particles mixed in the PRF membrane to assess if regeneration of
      new bone is possible. RESULTS AND CONCLUSION: This resulted in a rapid and
      complete healing with the decrease in the pocket depth and a gain in the clinical
      attachment level. Rapid regeneration of the periodontium can be achieved with
      bone substitutes by incorporating the various growth factors from autogenous
      blood.

PMID- 25756018
TI  - Metastatic adenocarcinoma of the mandible-a rare entity.
AB  - Metastasis of the liver and lung malignancies to the jaw bones is very rare and
      the mandible is the commonest site of involvement. The frequent primary sites for
      metastasis to jaw bones are breast in females and lungs in males. This is a case
      report of the metastatic adenocarcinoma of the mandible which originated from
      liver or lung. Diagnosis of such metastatic lesions is difficult and challenging
      to identify the primary site. 

PMID- 25756019
TI  - Lymphangioma of cheek region-an unusual presentation.
AB  - BACKGROUND AND OBJECTIVES: Lymphangiomas are benign hamartomatous tumors of the
      lymphatic vessels. A lymphatic malformation is a congenital defect that occurs
      during early embryonic development when the lymphatic vessels do not properly
      form. The vessels may become blocked and enlarged as lymphatic fluid collects in
      the vessels, forming a mass or a cyst. About 50% of all lesions are noted at
      birth and around 90% develop by 2 years of age. MATERIALS AND METHODS: We report
      the case of lymphangioma, with an unusual presentation in the cheek region
      resulting into vestibular obliteration and expanding to the left maxilla
      diagnosed on the basis of histopathology. The review of literature concerning the
      clinical and histological features as well as the proper management concerning
      this hamartomatous entity is included. RESULTS AND CONCLUSION: The various
      treatment modalities for lymphangioma are surgical excision, radiation therapy
      cryotherapy, electrocautery, sclerotherapy, steroid administration, embolization,
      ligation, laser surgery with Nd-YAG and CO2 and radiofrequency tissue ablation
      technique. An early diagnosis and intervention helps in reducing the functional,
      psychological disturbances and cosmetic disfigurement.

PMID- 25756020
TI  - Accidental injection of sodium hypochlorite instead of local anesthetic in a
      patient scheduled for endodontic procedure.
AB  - We present here a case of tissue destruction and paresthesia following the
      accidental injection of sodium hypochlorite instead of local anesthetic in a
      patient scheduled for endodontic procedure. The accident was managed by the local
      injection of steroid, debridement of necrotic tissue, daily dressings and
      medications. Wound healing was satisfactory at the end of 1 month. An extra-oral
      scar and a small area of paresthesia persisted even after 5 years. 

PMID- 25756021
TI  - Infra-orbital nerve block anesthesia-extended coverage using intra-oral 'molar
      approach'.
AB  - The maxillary teeth are supplied by the anterior, middle and posterior superior
      alveolar nerves. The anterior and middle superior alveolar (AMSA) nerves exit the
      skull from the infra-orbital foramen, where they can be blocked for procedures on
      the maxillary anteriors and premolars. Sometimes, the middle superior alveolar
      nerve has a variant course and is not blocked by the conventional block
      technique. A new technique has been described for blocking the AMSA nerves,
      keeping in view the alternate pathway of the middle superior alveolar nerve. 

PMID- 25756022
TI  - Wakeup call to manage oral cancers in India.

PMID- 25756023
TI  - Where Indian dentistry stands for the subject of oral biology? What should be a
      direction for the subject?

PMID- 25756024
TI  - Association of mitochondrial deoxyribonucleic acid mutation with polymorphism in
      CYP2E1 gene in oral carcinogenesis.
AB  - BACKGROUND: Oral carcinogenesis is a complex process affected by genetic as well
      as environmental factors. CYP2E1 gene is involved in metabolism of number of
      compounds and carcinogens. Its normal functioning is required for homeostasis of
      free radical. Mitochondrial deoxyribonucleic acid (mtDNA) is 10-100 times more
      susceptible to damage than nuclear DNA. Mitochondrial DNA large scale deletions
      are well documented in oral cancer. However, the relationship between CYP2E1 gene
      polymorphisms and mtDNA damage is still not documented in literature. MATERIALS
      AND METHODS: Case-control study involving 50 subjects was carried out.
      Deoxyribonucleic acid extraction was done from study subject tissue samples.
      Restriction fragment length polymorphism (RFLP) and polymerase chain reaction
      (PCR) amplification was done to confirm CYP2E1 gene polymorphisms. The PCR
      amplification was done for mtDNA 4977 bp deletion. Statistical analysis was
      carried out using SPSS version 11.5 with chi(2) tests. RESULTS: c1c1 and DD
      polymorphisms are prevalent in North Indian population having oral cancer. These
      polymorphisms are significantly associated with mtDNA 4977 bp deletion.
      CONCLUSION: Mitochondrial DNA damage induced by wild CYP2E1 forms and imperfect
      DNA repair in mtDNA may act synergistically to greatly enhance oral cancer risk.

PMID- 25756025
TI  - Two wound-covering materials in the surgical treatment of oral submucous
      fibrosis: a clinical comparison.
AB  - INTRODUCTION: Oral submucous fibrosis (OSMF), a chronic debilitating condition of
      the mouth, has been treated both surgically and non-surgically, but non-surgical
      methods yield inconsistent results. The surgical methods essentially comprise of
      bilateral sectioning of fibrous bands with or without coronoidectomy followed by
      covering of the surgical defect with a graft or a wound dressing material such as
      collagen sheet. MATERIALS AND METHODS: This study comprised 30 clinically
      diagnosed cases of OSMF. This study compared transposition of buccal pad fat
      graft with collagen sheet to cover the defect within the following parameters:
      pain, swelling, mouth opening, color of mucosa, palpability of fibrous bands, and
      suppleness of mucosa. RESULTS: We found significant difference in the
      postoperative mouth opening, an insignificant difference for post surgical
      morbidity and higher grades of surgical convenience in using collagen sheet as a
      wound dressing material. CONCLUSION: Collagen membrane is a superior method
      compared to transposition of the buccal pad of fat as a graft to cover the
      surgical wound in the treatment of OSMF of grade III and above.

PMID- 25756026
TI  - Prevalence and clinical characteristics of oral tori among outpatients in
      Northern Malaysia.
AB  - OBJECTIVES: The objectives of this study were to determine the prevalence and
      clinical characteristics of torus palatinus (TP) and torus mandibularis (TM) in
      Malaysian dental patients. METHODS: Thousand five hundred and thirty-two dental
      patients were examined for the presence of oral tori at the Faculty of Dentistry
      outpatient clinic, AIMST University. Factors such as race, age, sex, size, and
      shape of tori were studied. RESULTS: The prevalence rates were 12% for TP and
      2.8% for TM. A variation in the presence of tori among the three races in
      Malaysia-Chinese, Malays, and Indians-was noted, where the Chinese significantly
      had a higher prevalence of TP (17.9%) and TM (4.6%). Predominantly, tori were
      observed >40 years and older age group, and further both TP and TM were seen more
      commonly in women. Most TP were of smooth type (52.2%) and >2 cm (67.4%), while
      all TM were bilateral and nodular, plus most were <2 cm (67.4%). CONCLUSION:
      Presence of tori (TP and TM) was detected in 12.5% of the participants. The
      variations noted in the prevalence and clinical characteristics of tori among
      people of different races living in the same country reflect its multifactorial
      etiology. Both genetic and environmental factors are responsible for its
      occurrence, and particular races are more prone genetically where its expression
      is enhanced by environmental factors.

PMID- 25756027
TI  - Relationship between growth of facial morphology and chronologic age in preschool
      children with obstructive sleep apnea.
AB  - BACKGROUND: The purpose of this study was to evaluate the relationship between
      facial morphology using cephalometry and chronologic age in preschool children
      with obstructive sleep apnea (OSA). MATERIALS AND METHODS: From a group of
      lateral cephalometric radiographs taken of 35 children with OSA for diagnostic
      purposes, 15 were selected for the present investigation based on head position.
      The subjects consisted of preschool children with both OSA and primary dentition,
      all of them with a lowest documented SpO(2) <90% and a lowest 0 <AI. The control
      group included 15 preschool children with primary dentition and without enlarged
      tonsils or adenoids. RESULTS: The present findings reveal that, compared to the
      controls, OSA children had a narrower pharyngeal airway space related to OSA. In
      addition, we found that, although there were direct correlations between heights,
      nasal floor and corpus length, with chronologic age in the controls, there was no
      significant correlation between height, nasal floor length or corpus length with
      age in the OSA children. CONCLUSION: Obstructive sleep apnea in children may be
      associated with growth disturbances of the nasal floor and corpus length.

PMID- 25756028
TI  - Alveolar ridge augmentation using distraction osteogenesis: a clinical trial.
AB  - BACKGROUND: Severely resorbed ridges present a great challenge to prosthodontic
      rehabilitation. Available reconstructive options include autologous/alloplastic
      augmentation with questionable results, or regeneration of new bone under gradual
      and controlled tension using distraction osteogenesis. This study focused on use
      of distraction osteogenesis for the treatment of vertically deficient alveolar
      ridges to assess its feasibility and outcome. MATERIALS AND METHODS: Alveolar
      distraction osteogenesis (ADO) was studied at 10 different intra-oral, partial or
      complete edentulous sites. After a latency period of 5 days, distraction was
      carried out for 6-7 days at the rate of 0.5 mm every 12 hours (1 mm/day).
      Distractor was removed after a consolidation period of 12 weeks. RESULTS: The
      mean height gained at the 10 intra-oral sites was 4.8 mm with standard deviation
      of +/- 0.056. The mean follow-up period was 2 years. Complications of therapy
      included hardware failure, wound gape and extra-oral scar. The overall
      complication rate was 10%. CONCLUSION: Distraction osteogenesis is a promising
      option to aid uneventful prosthodontic rehabilitation of severe vertically
      resorbed alveolar ridges.

PMID- 25756029
TI  - Relationship of maxilla to cranial base in different facial types-a cephalometric
      evaluation.
AB  - BACKGROUND: Many conflicting opinions have been put forth in the dental
      literature concerning the maxilla and its relationship to craniofacial complex.
      In view of this fact, this cephalometric study was conducted to determine the
      relationship of maxilla to cranial base in different facial types. MATERIALS AND
      METHODS: The sample consists of 120 pretreatment lateral cephalogram, which were
      categorized into three groups, normodivergent, hypodivergent, and hyperdivergent.
      Each group consists of 20 males and 20 females. Descriptive statistics for 11
      variables were calculated. RESULTS AND CONCLUSION: The result of this study
      implies that in hyperdivergent subjects' sagittal maxillary base size was smaller
      and upper posterior facial height (UPFH) was increased in comparison to
      hypodivergent and normodivergent subjects. Upper posterior facial height has
      positive correlation with anterior facial height. Posterior maxillary position in
      relation to cranial base increases with increase in cranial flexural angle in
      hypodivergent subjects and vice versa in hyperdivergent subjects. Upper posterior
      facial height decreases with increase in cranial flexural angle in hypodivergent
      subjects and vice versa in hyperdivergent subjects.

PMID- 25756030
TI  - Biomaterials in periodontal osseous defects.
AB  - INTRODUCTION: Osseous defects in periodontal diseases require osseous grafts and
      guided tissue regeneration (GTR) using barrier membranes. The present study was
      undertaken with the objectives to clinically evaluate the osteogenic potential of
      hydroxyapatite (HA), cissus quadrangularis (CQ), and oxidized cellulose membrane
      (OCM) and compare with normal bone healing. MATERIALS AND METHODS: Twenty
      subjects with periodontitis in the age group ranging from 20 years to 40 years
      were selected from our outpatient department on the basis of presence of deep
      periodontal pockets, clinical probing depth >=5 mm, vertical osseous defects
      obvious on radiograph and two- or three-walled involvement seen on surgical
      exposure. Infrabony defects were randomly divided into four groups on the basis
      of treatment to be executed, such that each group comprised 5 defects. Group I
      was control, II received HA, III received CQ and IV received OCM. Probing depth
      and attachment level were measured at regular months after surgery. Defects were
      re-exposed using crevicular incisions at 6 months. RESULTS: There was gradual
      reduction in the mean probing pocket depth in all groups, but highly significant
      in the site treated with HA. Gain in attachment level was higher in sites treated
      with HA, 3.2 mm at 6 months. CONCLUSION: Hydroxyapatite and OCM showed good
      reduction in pocket depth, attachment level gain and osseous defect fill. Further
      study should be conducted by using a combination of HA and OCM in periodontal
      osseous defects with growth factors and stem cells.

PMID- 25756031
TI  - Role of stem cells in tooth bioengineering.
AB  - The creation of teeth in the laboratory depends upon the manipulation of stem
      cells and requires a synergy of all cellular and molecular events that finally
      lead to the formation of tooth-specific hard tissues, dentin, and enamel. This
      review focuses on the different sources of stem cells that have been used for
      making teeth in vitro. The search was performed from 1970 to 2012 and was limited
      to English language papers. The keywords searched on medline were 'stem cells and
      dentistry,' 'stem cells and odontoblast,' 'stem cells and dentin,' and 'stem
      cells and ameloblasts.' 

PMID- 25756032
TI  - Natural head position: key position for radiographic and photographic analysis
      and research of craniofacial complex.
AB  - The Frankfort horizontal is a useful compromise for studying skulls but not for
      orienting the natural head position (NHP) in the living because it is normally
      distributed around a true extracranial horizontal. Nonetheless, orthodontists
      dealing with living subjects, rather than inert crania, have used this Frankfort
      horizontal faithfully in cephalometry. Because the cant or inclination of all
      intracranial reference lines is subjected to biologic variation, they are
      unsuitable for meaningful cephalometric analysis. Registration of head posture in
      its natural position has the advantage that an extracranial vertical or a
      horizontal perpendicular to that vertical can be used as reference line for
      cephalometric analysis. Purpose of this paper is to provide an updated review of
      various methods to reproduce and record the NHP. 

PMID- 25756033
TI  - Unusual presentation of Kimura's disease involving the parotid gland in an Indian
      male: a case report and review of literature.
AB  - Kimura's disease (KD) is a rare chronic inflammatory disorder that involves the
      subcutaneous tissues and occurs predominantly in the head and neck region,
      frequently associated with regional lymphadenopathy or salivary gland
      involvement. Although, not an uncommon condition in the Asian countries, it is
      quite rare among the occidental civilization and in the western countries is more
      commonly diagnosed among Asian migrants. Kimura's disease is sometimes confused
      with angiolymphoid hyperplasia with eosinophilia, which occurs in the superficial
      skin of the head and neck region. The classical features of angiolymphoid
      hyperplasia with eosinophilia are characterized by a triad of painless
      subcutaneous masses in the head and neck region, blood and tissue eosinophilia,
      and markedly elevated immunoglobulin E (IgE) levels. Here, we report a case of a
      33-year-old Indian male with KD who presented with unilateral nodular swelling in
      the right parotid region. The diagnosis was based on characteristic
      histopathologic findings in conjunction with peripheral eosinophilia and elevated
      serum IgE levels. 

PMID- 25756034
TI  - Basal cell ameloblastoma-review of literature with report of three cases.
AB  - The ameloblastoma is the most common epithelial odontogenic tumor of the jaw with
      several histologic variants viz. follicular, plexiform, acanthomatous,
      desmoplastic, and granular cell and basal cell types. The basal cell
      ameloblastoma is a rare histological variant which tends to demonstrate
      microscopic features similar to cutaneous basal cell carcinoma and basaloid
      squamous cell carcinoma. In the current article we report three cases and review
      the literature of this rare tumor. 

PMID- 25756035
TI  - Peripheral adenomatoid odontogenic tumor: report of a rare case.
AB  - Adenomatoid odontogenic tumor is a benign odontogenic tumor with slow growth
      potential and exceptionally low recurrence rate. The tumor is predominantly found
      in females in the second decade of life, involving the maxilla more frequently
      than the mandible. The tumor presents in three variants-intrafollicular,
      extrafollicular, and peripheral. The peripheral variant is very rare and only few
      reports have been published. We present a rare case of peripheral adenomatoid
      odontogenic tumor in a 10-year-old male child in the anterior region of the
      mandible. 

PMID- 25756036
TI  - Early treatment outcomes of class II malocclusion with twin-block facial profile
      and cephalometric changes.
AB  - Esthetic improvement is highly valued by patients seeking orthodontic treatment.
      Subjects with a class II malocclusion are a good example of patients who seek
      treatment primarily for esthetic improvement. A young growing child with convex
      profile due to a small, retropositioned mandible, normal midface and lower tip
      trap is more suitable for functional appliance treatment. Functional appliances
      encourage adaptive skeletal growth by maintaining the mandible in a corrected
      forward position for a sufficient period of time to allow adaptive skeletal
      changes to occur in response to a functional stimulus. The aim of this article is
      to describe two cases of class II malocclusion in late mixed dentition period
      treated with twin-block. The cephalometric and facial profile changes have been
      discussed. 

PMID- 25756037
TI  - Modified functionally generated path technique for single complete denture
      against non-modified natural dentition.
AB  - BACKGROUND: A clinical report of a patient complaining of frequent fractures of
      her maxillary complete denture opposing dentulous mandibular arch is presented.
      MATERIALS AND METHODS: The patient was rehabilitated with a maxillary complete
      denture using modified functionally generated path technique to achieve
      harmonious occlusion between the complete denture and the natural dentition.
      DISCUSSION: Using the patient's own denture to record the functionally generated
      path made the technique much easier and also saved valuable chair-side time.
      Occlusal balancing in the trial denture bases gave us the flexibility to move the
      teeth slightly, or grind them in order to balance the occlusion. SUMMARY AND
      CONCLUSION: Our modification of the functionally generated path technique
      resulted in successful rehabilitation of the patient without any fracture of the
      prosthesis in the 2-year follow-up, and has saved valuable chair-side time and
      laboratory effort.

PMID- 25756038
TI  - Integrating psychosocial care into neuro-oncology: challenges and strategies.
AB  - Approximately 256,000 cases of malignant brain and nervous system cancer were
      diagnosed worldwide during 2012 and 189,000 deaths, with this burden falling more
      heavily in the developed world. Problematically, research describing the
      psychosocial needs of people with brain tumors and their carers and the
      development and evaluation of intervention models has lagged behind that of more
      common cancers. This may relate, at least in part, to poor survival outcomes and
      high morbidity associated with this illness, and stigma about this disease. The
      evidence base for the benefits of psychosocial care in oncology has supported the
      production of clinical practice guidelines across the globe over the past decade,
      with a recent mandate to integrate the psychosocial domain and measurement of
      distress into routine care. Clinical care guidelines for people with brain tumors
      have emerged, with a building focus on psychosocial and survivorship care.
      However, researchers will need to work intensively with health care providers to
      ensure future practice is evidence-based and able to be implemented across both
      acute and community settings and likely within existing resources. 

PMID- 25756039
TI  - Autism as a disorder of biological and behavioral rhythms: toward new therapeutic
      perspectives.
AB  - There is a growing interest in the role of biological and behavioral rhythms in
      typical and atypical development. Recent studies in cognitive and developmental
      psychology have highlighted the importance of rhythmicity and synchrony of motor,
      emotional, and interpersonal rhythms in early development of social
      communication. The synchronization of rhythms allows tuning and adaptation to the
      external environment. The role of melatonin in the ontogenetic establishment of
      circadian rhythms and the synchronization of the circadian clocks network
      suggests that this hormone might be also involved in the synchrony of motor,
      emotional, and interpersonal rhythms. Autism provides a challenging model of
      physiological and behavioral rhythm disturbances and their possible effects on
      the development of social communication impairments and repetitive behaviors and
      interests. This article situates autism as a disorder of biological and
      behavioral rhythms and reviews the recent literature on the role of rhythmicity
      and synchrony of rhythms in child development. Finally, the hypothesis is
      developed that an integrated approach focusing on biological, motor, emotional,
      and interpersonal rhythms may open interesting therapeutic perspectives for
      children with autism. More specifically, promising avenues are discussed for
      potential therapeutic benefits in autism spectrum disorder of melatonin combined
      with developmental behavioral interventions that emphasize synchrony, such as the
      Early Start Denver Model. 

PMID- 25756040
TI  - Twelve-month-old infants anticipatorily plan their actions according to expected
      object weight in a novel motor context.
AB  - Planning actions in anticipation of object weight is fundamental to skilled
      action production. The present study investigated whether infants can apply
      weight information gained from direct actions on objects in order to plan their
      actions according to object weight in a novel and indirect motor context. In the
      present study, two groups of 12-month-old infants were provided with experience
      acting directly on two blocks of different weights and colors (70 versus 470 g;
      red versus yellow). Subsequently, infants were administered a novel task in which
      the same blocks (standard condition; n = 60), or blocks of the reversed color
      weight pairings (switch condition; n = 60), were placed out-of-reach, on top of a
      cloth, and infants were encouraged to retrieve the block by acting on the cloth.
      Infants in the switch condition produced more failed cloth pulls when retrieving
      the 470 g block, due to inadequate generation of anticipatory force, relative to
      infants in the standard condition. This demonstrates that infants' force on the
      cloth was prospectively generated based on their mental representation of the
      supported block's weight, which was formed through their previous direct actions
      on the object. Thus, infants use information about the weight of an object in
      order to anticipate how to obtain that object in a novel and indirect problem
      solving context. 

PMID- 25756041
TI  - Comparative analysis of quinolone resistance in clinical isolates of Klebsiella
      pneumoniae and Escherichia coli from Chinese children and adults.
AB  - The objective of this study was to compare quinolone resistance and gyrA
      mutations in clinical isolates of Klebsiella pneumoniae and Escherichia coli from
      Chinese adults who used quinolone in the preceding month and children without any
      known history of quinolone administration. The antimicrobial susceptibilities of
      61 isolates from children and 79 isolates from adults were determined. The
      mutations in the quinolone resistance-determining regions in gyrA gene were
      detected by PCR and DNA sequencing. Fluoroquinolone resistance and types of gyrA
      mutations in isolates from children and adults were compared and statistically
      analyzed. No significant differences were detected in the resistance rates of
      ciprofloxacin and levofloxacin between children and adults among isolates of the
      two species (all P > 0.05). The double mutation Ser83->Leu + Asp87->Asn in the
      ciprofloxacin-resistant isolates occurred in 73.7% isolates from the children and
      67.9% from the adults, respectively (P = 0.5444). Children with no known history
      of quinolone administration were found to carry fluoroquinolone-resistant
      Enterobacteriaceae isolates. The occurrence of ciprofloxacin resistance and the
      major types of gyrA mutations in the isolates from the children were similar to
      those from adults. The results indicate that precautions should be taken on
      environmental issues resulting from widespread transmission of quinolone
      resistance. 

PMID- 25756042
TI  - Ethnogynaecological assessment of medicinal plants in Pashtun's tribal society.
AB  - The present study was designed to document detailed ethnogynaecological knowledge
      of selected remote regions of Pashtun's tribe in northwest Pakistan.
      Semistructured questionnaires were designed to collect ethnogynaecological and
      ethnographic data. Total of 51 medicinal plants belonging to 36 families were
      documented that were used by the women of studied regions for the treatment of 9
      types of gynaecological complaints. Majority of the plants (19) were found used
      against menses followed by 11 plants each for gonorrhea and pregnancy. Bannu
      region has high number of gynaecological plants (22) followed by Karak (15).
      Women of the regions mostly used whole plants (33%) and leaves (31%) for various
      ethnomedicinal preparation of gynae. Fic results showed that all ailments in
      different areas scored high consensus ranges between 0.6 and 1.00. Majority of
      the female respondents (44%) were aged between 61 and 70 years, of which most
      were illiterate. Women in the remote regions of Pakistan have tremendous
      traditional knowledge in utilizing medicinal plants for their reproductive
      health. Plants with high Fic values should be cross-checked for their in vitro
      and in vivo validation. Young girls should be educated on the importance of
      ethnogynaecological practices to conserve this valuable knowledge. 

PMID- 25756043
TI  - Differentiation between acute skin rejection in allotransplantation and T-cell
      mediated skin inflammation based on gene expression analysis.
AB  - Advances in microsurgical techniques and immunosuppressive medication have
      rendered transplantation of vascularized composite allografts possible, when
      autologous tissue is neither available nor sufficient for reconstruction.
      However, skin rejection and side effects of long-term immunosuppression still
      remain a major hurdle for wide adoption of this excellent reconstructive
      technique. Histopathologic changes during acute skin rejection in vascular
      composite allotransplantation often mimic inflammatory skin disorders and are
      hard to distinguish. Hence, the identification of diagnostic and therapeutic
      markers specific for skin rejection is of particular clinical need. Here we
      present novel markers allowing for early differentiation between rejection in
      hind limb allotransplantation and contact hypersensitivity. Assessment of Ccl7,
      Il18, and Il1b expression is most indicative of distinguishing skin rejection
      from skin inflammatory disorders. Gene expression levels varied significantly
      across skin types and regions, indicating localization specific mechanism of
      leukocyte migration and infiltration. Expression of Il12b, Il17a, and Il1b gene
      expression levels differed significantly between rejection and inflammation,
      independent of the skin type. In synopsis of the RNA expression profile and
      previously assessed protein expression, the Il1 family appears as a promising
      option for accurate skin rejection diagnosis and, as a following step, for
      development of novel rejection treatments. 

PMID- 25756044
TI  - Scaffolds from surgically removed kidneys as a potential source of organ
      transplantation.
AB  - End stage renal disease (ESRD) is a common disease, which relates to nearly 600
      million people in the total population. What is more, it seems to be a crucial
      problem from the epidemiological point of view. These facts lead to a further
      necessity of renal replacement therapy development connected with rising
      expenditures for the health care system. The aim of kidney tissue engineering is
      to develop and innovate methods of obtaining renal extracellular matrix (ECM)
      scaffolds derived from kidney decellularization. Recently, progress has been made
      towards developing a functional kidney graft in vitro on demand. In fact,
      decellularized tissues constitute ideal natural scaffolds, due to the
      preservation of native ECM architecture, as well as of cell-ECM binding domains
      critical in promoting cell attachment, migration, and proliferation. One of the
      potential sources of the natural scaffolds is the kidney, which cannot be
      transplanted immediately after excision. 

PMID- 25756045
TI  - Impact of ischemic preconditioning on outcome in clinical liver surgery: a
      systematic review.
AB  - BACKGROUND: Ischemia-reperfusion injury is a major cause of post-liver-surgery
      complications. Ischemic preconditioning (IPC) has been demonstrated to protect
      against ischemia-reperfusion injury. Clinical studies have examined IPC in liver
      surgery but with conflicting results. This systematic review aimed to evaluate
      the effects of IPC on outcome in clinical liver surgery. METHODS: An electronic
      search of OVID Medline and Embase databases was performed to identify studies
      that reported outcomes in patients undergoing liver surgery subjected to IPC.
      Basic descriptive statistics were used to summarise data from individual clinical
      studies. RESULTS: 1093 articles were identified, of which 24 met the inclusion
      criteria. Seven topics were selected and analysed by subgroup. There were 10
      studies in cadaveric liver transplantation, 2 in living-related liver
      transplantation, and 12 in liver resection. IPC decreases hepatocellular damage
      in liver surgery as determined by transaminases but does not translate to any
      significant clinical benefit in orthotopic liver transplant or liver resection.
      CONCLUSIONS: Available clinical evidence does not support routine use of IPC in
      liver surgery as it does not offer any apparent benefit in perioperative outcome.
      Further clinical studies will need to be carried out to determine the subset of
      patients that will benefit from IPC.

PMID- 25756046
TI  - Effect of teriparatide on unstable pertrochanteric fractures.
AB  - We retrospectively analyzed the radiographic and clinical outcomes of unstable
      pertrochanteric fractures (AO/OTA 31-A2) in 44 patients who underwent dynamic hip
      screw (DHS) fixation and compared the results with 29 patients who received
      teriparatide in addition to DHS fixation. A significantly shorter time for
      fracture healing was recorded in the teriparatide-treated group than in the
      control group. Rates of lag screw sliding, femoral shortening, and varus collapse
      were all significantly reduced in the teriparatide-treated group. There were no
      significant differences with regard to superficial wound infection, pneumonia,
      urinary tract infection, mortality, malunion, and cutting of the lag screw. The
      mean overall mobility scores were significantly better in the teriparatide
      treated group at 3 and 6 months (P < 0.001 and P < 0.001, resp.) but not at 12
      months or the last follow-up. The pain scores were also significantly better in
      the teriparatide-treated group at 3 and 6 months (P = 0.040 and P = 0.041, resp.)
      but not at 12 months or the last follow-up. Teriparatide improves radiographic
      outcomes and yields better clinical outcomes at 3 and 6 months postoperatively.
      The improvement in union time may be important for elderly populations with
      unstable pertrochanteric fractures to enable them to return to daily activities
      and reduce morbidity and mortality. 

PMID- 25756047
TI  - Analysis of circulating vascular endothelial growth factor and its soluble
      receptors in patients with different forms of chronic urticaria.
AB  - BACKGROUND: Vascular endothelial growth factor (VEGF) is a powerful enhancer of
      vascular permeability and inflammatory response; however its significance in
      chronic urticaria is poorly recognised. AIM: To compare free circulating levels
      of VEGF and its soluble receptors (sVEGFR1 and VEGFR2) in patients with different
      forms of chronic urticaria. METHODS: The concentrations of VEGF and its receptors
      in plateletpoor plasma (PPP)/plasma were measured using enzyme-linked
      immunosorbent assay in chronic urticaria: (1) chronic spontaneous urticaria (CSU)
      with positive autologous serum skin test (ASST), (2) CSU with negative response
      to ASST, (3) CSU with concomitant euthyroid Hashimoto's thyroiditis
      (CSU/Hashimoto), (4) delayed pressure urticaria (DPU), and the healthy subjects.
      RESULTS: There were no significant differences in VEGF concentration in PPP
      between CSU groups and the healthy subjects. Contrary, VEGF concentration was
      significantly higher in DPU and CSU/Hashimoto patients as compared with the
      healthy subjects and CSU groups. Furthermore, VEGF value in CSU/Hashimoto
      patients during the remission was similar to that of the active period and
      significantly higher than the healthy subjects; VEGF concentration was
      significantly correlated with TSH. Plasma concentrations of sVEGF1 and sVEGF2
      were similar in chronic urticaria patients and the healthy subjects. CONCLUSIONS:
      Increased free circulating VEGF concentration may result from the urticarial
      process itself as well as concomitant Hashimoto's thyroiditis.

PMID- 25756048
TI  - Resistance to fracture of dental roots obturated with different materials.
AB  - The aim of this study was to compare the vertical fracture resistance of roots
      obturated with different root canal filling materials and sealers. Crowns of 55
      extracted mandibular premolar teeth were removed to provide root lengths of 13
      mm. Five roots were saved as negative control group (canals unprepared and
      unfilled). Fifty root canals were instrumented and then five roots were saved as
      positive control group (canals prepared but unfilled). The remaining 45 roots
      were randomly divided into three experimental groups (n = 15 root/group) and
      obturated with the following procedures: in group 1, glass ionomer-based sealer
      and cone (ActiV GP obturation system); in group 2, bioceramic sealer and cone
      (EndoSequence BC obturation system); and in group 3, roots were filled with
      bioceramic sealer and cone (Smartpaste bio obturation system). All specimens were
      tested in a universal testing machine for measuring fracture resistance. For each
      root, the force at the time of fracture was recorded in Newtons. The statistical
      analysis was performed by using Kruskal-Wallis and post hoc test. There were no
      significant differences between the three experimental groups. The fracture
      values of three experimental and negative control groups were significantly
      higher than the positive control group. Within the limitations of this study, all
      materials increased the fracture resistance of instrumented roots.

PMID- 25756050
TI  - Endoscopic sphincterotomy with large balloon dilation versus endoscopic
      sphincterotomy for bile duct stones: a systematic review and meta-analysis.
AB  - The safety and efficacy of endoscopic sphincterotomy with large balloon dilation
      (EPLBD) are unclear. This study compares the safety and efficacy between EPLBD
      and endoscopic sphincterotomy (EST). PATIENTS AND METHODS: Literatures were
      searched for randomized controlled trials in PUBMED, EMBASE, and Cochrane
      Library. Outcome measurements included adverse events; stone removal rate;
      requirement of mechanical lithotripsy. RESULTS: Four RCTs with a total of 596
      patients were included. Three RCTs compared EPLBD versus EST alone for stone
      removal; one RCT compared EPLBD versus EST plus mechanical lithotripsy for stone
      removal. Pooled data from three RCTs showed that there was no significant
      difference in the adverse event of ERCP. A significantly higher cholangitis rate
      was seen in patients who received EST plus mechanical lithotripsy, compared to
      those treated with EPLBD (13.3% versus 0.0, P = 0.026). No statistical difference
      was found between EPLBD and EST for stone removal rate. Significant differences
      in requirement of mechanical lithotripsy were seen with removal of large stones
      (>15 mm), with EPLBD reducing the use of mechanical lithotripsy (RR: 0.73; 95%
      CI: 0.54-0.99). CONCLUSIONS: EPLBD and EST have similar efficacy and safety for
      bile duct stones clearance. With larger stones, EPLBD can reduce requirement of
      mechanical lithotripsy.

PMID- 25756049
TI  - MicroRNA and mRNA features of malignant pleural mesothelioma and benign asbestos
      related pleural effusion.
AB  - INTRODUCTION: We investigated the expression of microRNAs and mRNAs in pleural
      tissues from patients with either malignant pleural mesothelioma or benign
      asbestos-related pleural effusion. METHODS: Fresh frozen tissues from a total of
      18 malignant pleural mesothelioma and 6 benign asbestos-related pleural effusion
      patients were studied. Expression profiling of mRNA and microRNA was performed
      using standard protocols. RESULTS: We discovered significant upregulation of
      multiple microRNAs in malignant pleural mesothelioma compared to benign asbestos
      related pleural effusion. Hsa-miR-484, hsa-miR-320, hsa-let-7a, and hsa-miR-125a
      5p were able to discriminate malignant from benign disease. Dynamically regulated
      mRNAs were also identified. MET was the most highly overexpressed gene in
      malignant pleural mesothelioma compared to benign asbestos-related pleural
      effusion. Integrated analyses examining microRNA-mRNA interactions suggested
      multiple altered targets within the Notch signaling pathway. CONCLUSIONS:
      Specific microRNAs and mRNAs may have diagnostic utility in differentiating
      patients with malignant pleural mesothelioma from benign asbestos-related pleural
      effusion. These studies may be particularly helpful in patients who reside in a
      region with a high incidence of mesothelioma.

PMID- 25756051
TI  - A novel aqueous micellar two-phase system composed of surfactant and sorbitol for
      purification of pectinase enzyme from Psidium guajava and recycling phase
      components.
AB  - A novel aqueous two-phase system composed of a surfactant and sorbitol was
      employed for the first time to purify pectinase from Psidium guajava. The
      influences of different parameters, including the type and concentration of the
      surfactant and the concentration and composition of the surfactant/sorbitol
      ratio, on the partitioning behavior and recovery of pectinase were investigated.
      Moreover, the effects of system pH and the crude load on purification fold and
      the yield of purified pectinase were studied. The experimental results indicated
      that the pectinase was partitioned into surfactant-rich top phase, and the
      impurities were partitioned into the sorbitol-rich bottom phase with the novel
      method involving an ATPS composed of 26% (w/w) Triton X-100 and 23% (w/w)
      sorbitol at 54.2% of the TLL crude load of 20% (w/w) at pH 6.0. The enzyme was
      successfully recovered by this method with a high purification factor of 15.2 and
      a yield of 98.3%, whereas the phase components were also recovered and recycled
      at rates above 96%. This study demonstrated that this novel ATPS method can be
      used as an efficient and economical alternative to the traditional ATPS for the
      purification and recovery of the valuable enzyme. 

PMID- 25756052
TI  - Gender-specific associations of serum antibody to Porphyromonas gingivalis and
      inflammatory markers.
AB  - It remains unclear whether serum antibody titer against Porphyromonas gingivalis
      (Pg) and inflammatory components lead to periodontal deterioration in each
      gender, as periodontal and systemic status is influenced by gender. The present
      study investigates the gender-specific probable effects of titer against Pg and
      inflammatory markers on periodontal health status in a longitudinal study. A
      retrospective study design was used. At two time points over an 8-year period (in
      2003 and 2011), 411 individuals (295 males with a mean age of 57.6 +/- 11.2 years
      and 116 females with a mean age of 59.2 +/- 10.3 years) were surveyed.
      Periodontal status, serum antibody titer against Pg, and high-sensitive C
      reactive protein (hsCRP) were evaluated. Poisson regression analyses revealed
      that the elevated titer against Pg and hsCRP significantly predicted the
      persistence of periodontal disease 8 years later in females with periodontal
      disease in 2003. Elevated hsCRP was significantly associated with the incidence
      of periodontal disease 8 years later in females who were periodontally healthy in
      2003. Males had a weaker association among titer against Pg, inflammatory
      markers, and periodontal disease. These findings suggest that immune response to
      Pg infection in addition to inflammatory components affects periodontal
      deterioration in females. 

PMID- 25756053
TI  - Importance of maternal diabetes on the chronological deregulation of the
      intrauterine development: an experimental study in rat.
AB  - We investigated whether maternal diabetes induced in rats using streptozotocin
      (STZ) on Day 5 of pregnancy affects the intrauterine developmental timeline. A
      total of 30 pregnant Sprague-Dawley diabetic rats (DRs) and 20 control rats (CRs)
      were used to obtain 21-day fetuses (F21) and newborn (NB) pups. Gestational age,
      weight, and body size were recorded as were the maxillofacial morphometry and
      morphohistological characteristics of the limbs. In DRs, pregnancy continued for
      ~1.7 days, and delivery occurred 23 days postcoitus (DPC). In this group, the
      number of pups was lower, and 13% had maxillofacial defects. F21 in the DR group
      had lower weights and were smaller; moreover, the morphological characteristics
      of the maxillofacial structures, derived from the neural crest, were discordant
      with their chronological gestational age, resembling 18- to 19-day-old fetuses.
      These deficiencies were counterbalanced in NB pups. We conclude that
      hyperglycemia, which results from maternal diabetes and precedes embryo
      implantation, deregulates the intrauterine developmental timeline, restricts
      embryo-fetal growth, and primarily delays the remodeling and maturation of the
      structures derived from neural crest cells. 

PMID- 25756055
TI  - Neobenedenia melleni-specific antibodies are associated with protection after
      continuous exposure in Mozambique tilapia.
AB  - Neobenedenia melleni is a significant monogenean pathogen of fish in aquaculture
      facilities and public aquaria. Immunity after exposure to live N. melleni is well
      established, but the mechanisms of immunity remain unclear. In this study,
      tilapia (Oreochromis mossambicus) were continuously exposed to N. melleni over a
      four-month period and assessed for immunity as determined by a reduction in the
      number of parasites dislodged from the experimental animals during freshwater
      immersion. Specific mucosal and systemic antibody levels were by determined via
      enzyme-linked immunosorbent assay. At 45 days postexposure (DPE), fish displayed
      high parasite loads and baseline levels of mucosal antibodies. At 102 and 120 DPE
      parasite loads were significantly decreased, and antibody levels were
      significantly increased for mucus and plasma samples. The correlation between
      immunity (reduction in parasite load) and an increased humoral antibody response
      suggests a key role of antibody in the immune response. This is the first report
      of immunity against N. melleni that is associated with specific mucosal or
      systemic antibodies. 

PMID- 25756054
TI  - Long-lasting production of new T and B cells and T-cell repertoire diversity in
      patients with primary immunodeficiency who had undergone stem cell
      transplantation: a single-centre experience.
AB  - Levels of Kappa-deleting recombination excision circles (KRECs), T-cell receptor
      excision circles (TRECs), and T-cell repertoire diversity were evaluated in 1038
      samples of 124 children with primary immunodeficiency, of whom 102 (54 with
      severe combined immunodeficiency and 48 with other types of immunodeficiency)
      underwent hematopoietic stem cell transplantation. Twenty-two not transplanted
      patients with primary immunodeficiency were used as controls. Only data of
      patients from whom at least five samples were sent to the clinical laboratory for
      routine monitoring of lymphocyte reconstitutions were included in the analysis.
      The mean time of the follow-up was 8 years. The long-lasting posttransplantation
      kinetics of KREC and TREC production occurred similarly in patients with severe
      combined immunodeficiency and with other types of immunodeficiency and, in both
      groups, the T-cell reconstitution was more efficient than in nontransplanted
      children. Although thymic output decreased in older transplanted patients, the
      degree of T-cell repertoire diversity, after an initial increase, remained stable
      during the observation period. However, the presence of graft-versus-host disease
      and ablative conditioning seemed to play a role in the time-related shaping of T
      cell repertoire. Overall, our data suggest that long-term B- and T-cell
      reconstitution was equally achieved in children with severe combined
      immunodeficiency and with other types of primary immunodeficiency. 

PMID- 25756056
TI  - IL-31 is overexpressed in lichen planus but its level does not correlate with
      pruritus severity.
AB  - BACKGROUND: Pruritus is one of the major features of lichen planus (LP); however,
      its pathogenesis remains largely unknown. Objective. The aim of our study was to
      analyze the role of IL-31 in the pathogenesis of pruritus in LP. MATERIALS AND
      METHODS: The study group included 22 patients with LP. Control group consisted of
      14 healthy volunteers. All subjects underwent thorough examination. Pruritus
      severity was evaluated with the visual analogue scale (VAS) and the 12-item Itch
      Questionnaire. IL-31 expression in the skin was assessed using semiquantitative
      immunofluorescence analysis. RESULTS: Pruritus maximal intensity according to VAS
      was 6.5 +/- 2.7 points and according to the 12-item Itch Questionnaire 6.9 +/-
      2.8 points. Lesional LP skin showed significantly higher IL-31 expression
      compared to healthy skin (P < 0.001). The most abundant immunofluorescence was
      observed within granular layer. However, there was no correlation between
      expression of IL-31 and pruritus intensity assessed according to VAS (VASmax: rho
      = -0.08, P = 0.73), as well as 12-item Itch Questionnaire: rho = -0.11, P = 0.65.
      CONCLUSIONS: Pruritus is a very common symptom of LP. For the first time we have
      demonstrated that IL-31 is overexpressed in the lesional skin of LP but its
      expression does not correlate with intensity of pruritus.

PMID- 25756057
TI  - Sex hormones in allergic conjunctivitis: altered levels of circulating androgens
      and estrogens in children and adolescents with vernal keratoconjunctivitis.
AB  - PURPOSE: Vernal keratoconjunctivitis (VKC) is a chronic allergic disease mainly
      affecting boys in prepubertal age and usually recovering after puberty. To
      evaluate a possible role of sex hormones in VKC, serum levels of sex hormones in
      children and adolescents with VKC were assessed. METHODS: 12 prepubertal and 7
      early pubertal boys with active VKC and 6 male patients with VKC in remission
      phase at late pubertal age and 48 healthy age and sex-matched subjects were
      included. Serum concentration of estrone, 17 beta-estradiol,
      dehydroepiandrosterone-sulfate, total testosterone and free testosterone,
      dihydrotestosterone (DHT), cortisol, delta-4-androstenedione, follicle
      stimulating hormone, luteinizing hormone, and sex-hormones binding globuline
      (SHBG) were evaluated. RESULTS: Serum levels of Estrone were significantly
      increased in all groups of patients with VKC when compared to healthy controls (P
      < 0.001). Prepubertal and early pubertal VKC showed a significant decrease in DHT
      (P = 0.007 and P = 0.028, resp.) and SHBG (P = 0.01 and P = 0.002, resp.) when
      compared to controls and serum levels of SHBG were increased in late pubertal VKC
      in remission phase (P = 0.007). CONCLUSIONS AND RELEVANCE: VKC patients have
      different circulating sex hormone levels in different phases of the disease and
      when compared to nonallergic subjects. These findings suggest a role played by
      sex hormones in the pathogenesis and/or activity of VKC.

PMID- 25756058
TI  - Silicone intubation indications in external dacryocystorhinostomy.

PMID- 25756059
TI  - Urgent Eye Care in the UK Increased Demand and Challenges for the Future.

PMID- 25756060
TI  - Pachychoroid diseases of the macula.
AB  - Advances in optical coherence tomography have enabled a better appreciation of
      the role of pathologic choroidal changes in a variety of retinal disease. A
      "pachychoroid" (pachy-[prefix]: thick) is defined as an abnormal and permanent
      increase in choroidal thickness often showing dilated choroidal vessels and other
      structural alterations of the normal choroidal architecture. Central serous
      chorioretinopathy is just one of several pachychoroid-related macular disorders.
      This review summarizes the current state of knowledge of the pachycoroid spectrum
      and the hallmark features seen with multimodal imaging analysis of these
      entities. 

PMID- 25756061
TI  - Iris-fixated intraocular lenses for ametropia and aphakia.
AB  - Implantation of intraocular lens with Iris-fixation is a safe, efficient and
      predictable surgical procedure, which empowers the refractive surgeon with
      singular capabilities. Among their advantages are the reversibility, preservation
      of accommodation and a broad spectrum of ametropic correction. This lens also
      appears to be a valid option, with a favorable complication rate, for the
      treatment of aphakic eyes without capsular support. This article is a review of
      iris-fixated intraocular lenses and considers their principal indications,
      complications, and outcomes. 

PMID- 25756062
TI  - Subclinical Macular Edema Detected by Spectral-domain Optical Coherence
      Tomography (SD-OCT) in HLA-B27 Positive Anterior Uveitis.
AB  - PURPOSE: To assess foveal thickness by spectral-domain optical coherence
      tomography (SD-OCT) during acute anterior uveitis (AAU) in HLA-B27 patients.
      METHODS: Foveal thickness was measured at baseline and after clinical resolution
      of the uveitis. Data of the affected eyes of 11 patients were compared to those
      of a fellow, healthy eyes and to those of counterpart volunteers. RESULTS: At
      baseline mean foveal thickness was 190 +/- 28 um in affected eyes, 166 +/- 20 um
      in fellow eyes (p < 0.001), and 162+/-14 um in control group (p = 0.01). On the
      second OCT evaluation, no significant change was observed in affected eyes while
      the difference versus fellow eyes and control group remained statistically
      significant. CONCLUSIONS: A significant increase in foveal thickness was observed
      in eyes with HLA -B27 AAU when compared with healthy eyes. The difference
      persisted for at least one month, despite full clinical and functional recovery.

PMID- 25756063
TI  - Cat-scratch disease: unusual perivascular chorioretinal lesions.
AB  - This study is a case report of bilateral perivascular chorioretinal lesions
      associated with Bartonella henselae. A 37-year-old woman presented with headache
      and blurred vision in both eyes aggravating occasionally during five years. She
      was otherwise healthy, with best-corrected visual acuities were 20/20 in both
      eyes. History of close contact with cats was more than merely eye-catching upon
      examination of her fundus. In both eyes, fundi were coated with yellow-brown
      pigmented perivenous chorioretinal lesions along the superotemporal and
      inferotemporal vascular arcades and their branches. The perivenous lesions were
      associated with vascular fibrous bands and corresponding changes in vascular
      calibers. There were no associated intraocular inflammatory signs in both eyes.
      The serologic tests confirmed the diagnosis of cat-scratch disease. The patient
      received no treatment, and she was followed for three years without any signs of
      ocular inflammation. 

PMID- 25756064
TI  - The influence of functional fitness and cognitive training of physical
      disabilities of institutions.
AB  - According to an investigation done by Taiwan Ministry of the Interior in 2013,
      there was more than 90% of the disability care institutions mainly based on life
      care. Previous studies have shown that individuals can effectively improve
      physical and cognitive training, improved in independent living and everyday
      competence. The purpose of the study was to investigate influence of the
      intervention program applying functional fitness and cognitive training to
      disabled residents in the institution. The subjects were disabled persons of a
      care institution in southern Taiwan and were randomly divided into training and
      control groups, both having 17 subjects. The age of the subjects was between 56
      and 98 years with a mean age of 79.08 +/- 10.04 years; the subjects of training
      group implemented 12 weeks of training on physical and cognitive training, while
      the control group subjects did not have any training program. The results
      revealed that subjects of the training group have significantly improved their
      functional shoulder rotation flexibility of left and right anterior hip muscle
      group flexibility of right, sitting functional balance of left and right, naming,
      attention, delayed recall, orientation, and Montreal cognitive assessment (MOCA).
      The study suggested developing physical fitness programs and physical and
      cognitive prescriptions for the disabled people of the institutions. 

PMID- 25756065
TI  - Aclidinium/formoterol fixed-dose combination for the treatment of chronic
      obstructive pulmonary disease.
AB  - This review will be focused on the development of aclidinium bromide/formoterol
      fumarate (ACLI/FORM) fixed-dose combinations (FDC) that have been granted
      marketing authorization by the European Commission to be used as a maintenance
      bronchodilator treatment to relieve symptoms in adult patients with chronic
      obstructive pulmonary disease (COPD). ACLI/FORM FDC has been studied in 2 pivotal
      trials involving over 3,400 patients with COPD, in which it was compared with
      ACLI alone, FORM alone and placebo. The addition of FORM to ACLI resulted in
      greater bronchodilation than FORM or ACLI alone. ACLI/FORM FDC was also shown to
      increase the percentage of patients who had an improvement in symptoms and health
      related quality of life compared with monotherapies. The frequency of side
      effects reported with ACLI/FORM FDC was low and their nature did not raise any
      major safety concern. 

PMID- 25756066
TI  - Bazedoxifene/conjugated estrogens combination for the treatment of the vasomotor
      symptoms associated with menopause and for prevention of osteoporosis in
      postmenopausal women.
AB  - The decrease of estrogen in postmenopausal women has been associated with the
      presence of different symptoms such as vasomotor symptoms, vulvovaginal atrophy,
      bone loss, sleep disturbances, and mood and sexual activity alterations. Hormone
      replacement therapy with estrogen and progestins has been used to improve
      menopausal symptoms; however, there are still concerns regarding its safety and
      tolerability, as some progestins have been shown to increase breast cancer and
      cardiovascular risk. Bazedoxifene is a third-generation selective estrogen
      receptor modulator (SERM) used for osteoporosis management in postmenopausal
      women at fracture risk that has demonstrated a powerful antiestrogenic effect on
      the endometrium. Today we have a new alternative called the tissue-selective
      estrogen complex (TSEC), which combines bazedoxifene and conjugated estrogens and
      is designed not only to improve menopausal symptoms and vulvovaginal atrophy but
      also to prevent bone loss. Therefore, it maintains the benefits of estrogen
      therapy while antagonizing the stimulation effects on the endometrium and mammary
      gland without the effects associated with progestins. 

PMID- 25756067
TI  - Delamanid for the treatment of pulmonary multidrug-resistant tuberculosis.
AB  - Out of a handful of new drugs currently in clinical trials for the treatment of
      tuberculosis, delamanid, a nitro-dihydro-imidazole derivative, has successfully
      emerged. Delamanid is a novel mycolic acid biosynthesis inhibitor that is equally
      potent against drug-sensitive as well as drug-resistant Mycobacterium
      tuberculosis. One of the strongest points for delamanid is its inability to be
      metabolized by cytochrome P450 enzymes, making it a promising candidate to be
      used in combination therapies for the treatment of tuberculosis and HIV.
      Additionally, it has successfully completed phase II efficacy trials and has
      received conditional marketing authorization from the European Medicines Agency. 

PMID- 25756068
TI  - The year's new drugs & biologics 2014 - Part II: trends & challenges.
AB  - 2014 was a year of continued high activity in the pharma and biotech industry, as
      evidenced in part I of this annual two-part review article published last month
      in this journal (1). As of December 23, 2014, a total of 55 new chemical and
      biological entities had reached their first markets worldwide, together with
      another 29 important new line extensions. Another 19 products were approved for
      the first time during the year but not yet launched by December 23. Furthermore,
      during the now-traditional year-end sprint, several regulatory agencies issued
      last-minute approvals for other compounds that missed the deadline for inclusion
      in that article, bringing the total of new approvals for the year to a somewhat
      higher number. In addition to the successful development, registration and launch
      of new drugs and biologics, there are various other trends and tendencies that
      serve as indicators of the overall health and status of the industry. These
      include the pursuit of novel programs designed by regulators to stimulate the
      development of drugs for diseases that are currently under-treated; the regular
      and pragmatic culling by companies of their R&D pipelines; and the decision to
      unify pipelines, portfolios and sales forces through mergers and acquisitions. 

PMID- 25756069
TI  - Generic Pharmaceutical Association (GPhA) - 2015 Annual Meeting (February 9-11,
      2015 - Miami Beach, Florida, USA).
AB  - The Generic Pharmaceutical Association (GPhA) chairman Craig Wheeler (Momenta
      Pharmaceuticals), welcomed attendees to the 2015 Annual Meeting by reflecting on
      the contributions of the generic industry over the past year and some of the
      challenges that lie ahead. In 2014, 86% of prescriptions dispensed in the U.S.
      were generic, contributing to the USD 1.4 trillion savings generated by the
      industry since its inception; however, there are still many challenges to face,
      including consolidation of customers, lag in Abbreviated New Drug Application
      (ANDA) approval timelines, restrictive Risk Evaluation and Mitigation Strategy
      (REMS) programs and labeling legislations. The continued drive into the branded
      business by many GPhA member companies has resulted in the association planning a
      structural division for companies involved in biologic and biosimilar products.
      During the 3-day meeting, attendees listened to expert panels discuss major
      business, regulatory and market trends developing in the generic industry, with
      insights from the U.S. Food and Drug Administration (FDA) and market analysts.
      The meeting also provided attendees with numerous opportunities to socialize and
      network with key decision makers in the industry. 

PMID- 25756070
TI  - How I changed my practice in the last five years and what is likely to change in
      the next five years.

PMID- 25756071
TI  - Efficacy and side effects of antibiotics in the treatment of acute
      rhinosinusitis: a systematic review.
AB  - BACKGROUND: Acute rhinosinusitis (ARS) is one of the most common diagnoses for
      which an antibiotic is prescribed. Although the usage of antibiotics in the
      treatment of mild, moderate or uncomplicated ARS is not recommended by most
      international guidelines, overuse of antibiotics is still an alarming problem
      among patients and healthcare practitioners. We thus sought to review the
      evidence available through a systematic review of the existing literature on
      antibiotic usage in ARS. METHODOLOGY: A search of the PubMed database was
      conducted for studies on antibiotic and placebo usage in the treatment of ARS.
      RESULTS: A total of 31 random control trials (RCT) reporting the clinical
      efficacy of treating ARS and side effects of using cefuroxime axetil,
      telithromycin, amoxicillin/potassium clavulanate, levofloxacin, moxifloxacin and
      clarithromycin were included in the review. Among them, 9 studies were performed
      double-blinded with placebo controls. The results showed that while antibiotics
      are more efficacious than placebos in the treatment of ARS, the risks of
      potential side effects need to be weighed against the potential benefit that
      antibiotics give to the patient. This is especially pertinent as usage of the
      placebo has shown to be almost as efficacious as using the antibiotic therapy,
      and also much safer. CONCLUSION: The usage of antibiotics in ARS is widespread
      and there seems to be only slight added benefit in the usage of antibiotics over
      placebo in the treatment of ARS. Hence, larger scale studies should be done in
      the future to confirm the results of these studies.

PMID- 25756072
TI  - Does time to endoscopic sinus surgery impact outcomes in Chronic Rhinosinusitis?
      Prospective findings from the National Comparative Audit of Surgery for Nasal
      Polyposis and Chronic Rhinosinusitis.
AB  - OBJECTIVES: Patients with chronic rhinosinusitis refractory to medical management
      undergo elective surgery. The time from initial diagnosis to surgery varies
      considerably. The impact of this delay on surgical success has never previously
      been evaluated. DESIGN: First-time patients within the National Comparative Audit
      of Surgery for Nasal Polyposis and Chronic Rhinosinusitis were grouped based on
      time to surgery: 1) Early cohort: %lt; 12 months; 2) Mid cohort: 12-60 months;
      and 3) Late cohort: > 60 months. Co-morbidities and preoperative CT scores were
      analysed for all patients. MAIN OUTCOME MEASURES: The 22-item Sino-Nasal Outcome
      Test scores (SNOT-22) were collected at 0, 3, 12 and 60-months. Absolute and
      relative SNOT-22 changes from baseline were evaluated. RESULTS: Asthma and
      allergies were significantly more prevalent in the Late versus the Early and Mid
      cohorts. In addition, patients in the Late cohort had greater symptom burden on
      the SNOT-22 and more extensive preoperative radiographic disease as determined by
      Lund-Mackay (LM) scores. SNOT-22 scores demonstrated greater percentage
      improvements in the Early versus the Mid- and Late cohorts, at all time points
      after surgery. At 12 and 60 months after surgery, significantly more patients in
      the Early group achieved a clinically important change in SNOT-22 scores compared
      with the other groups. These differences were maintained when cohorts were
      matched for preoperative co-morbidities. CONCLUSION: Patients with asthma and/or
      allergies are more likely to experience delayed surgical intervention versus
      other patients. Overall, patients with delayed surgery reported less improvement
      in SNOT-22 scores than patients treated at earlier time points, regardless of co
      morbid status. Delaying surgical intervention may worsen long term clinical
      outcomes.

PMID- 25756073
TI  - Does time to endoscopic sinus surgery impact outcomes in chronic rhinosinusitis?
      Retrospective analysis using the UK clinical practice research data.
AB  - BACKGROUND: Patients with chronic rhinosinusitis (CRS) refractory to medical
      management may elect endoscopic sinus surgery (ESS). Recent data showed that
      clinical outcomes of patients treated earlier outperformed those of patients
      treated later in the disease continuum. In this study, CRS-related healthcare
      utilisation of patients treated early versus late was analysed using the UK-based
      Clinical Practice Research Database. METHODS: Two cohorts ("Early Cohort": ESS
      within 12 months of first CRS diagnosis, versus "Late Cohort": >= 5 years from
      diagnosis to ESS) were matched for age, gender, asthma, polyposis. Healthcare
      needs related to CRS were analysed post-operatively for 5 years. RESULTS:
      Patients in the Late cohort used significantly more CRS-related care than
      patients in the Early cohort visits and 0.54 prescriptions per patient per year.
      A sub-analysis of patients with and without asthma indicated that patients in the
      Late cohort without asthma had healthcare needs equivalent to patients in the
      Early cohort with asthma. CONCLUSION: Delayed surgical intervention for CRS is
      associated with greater post-operative healthcare needs than ESS within 12 months
      of first CRS diagnosis.

PMID- 25756074
TI  - Heredity of nasal polyps.
AB  - BACKGROUND: Nasal polyps is a common disease but little is known about its'
      pathogenesis. Our hypothesis was that there are genetic factors involved in the
      development of this disease. The aim of this study was to examine close relatives
      of patients with nasal polyps and comparing them with a general population with
      regard to prevalence of polyps. METHODOLOGY: Patients with nasal polyps who
      attended the clinic were recruited to the study and were asked whether they had
      any close adult relatives (siblings, parents or children). We intended to recruit
      two relatives per patient, one of each gender, for nasal endoscopy. The
      prevalence of nasal polyps in these relatives was compared with the prevalence of
      nasal polyps in a general population. RESULTS: During a 4-year period, 368
      patients and 410 relatives were recruited to the study. Although we were unable
      to recruit two close relatives for every patient, we were able to calculate nasal
      polyp prevalence within families as being 19.2%. Compared with the prevalence of
      nasal polyps among individuals in a general Swedish population from the same
      geographical area, the relative risk for polyps among relatives was almost five
      times higher. CONCLUSION: This study strongly indicates that heredity is a factor
      of importance for development of nasal polyps.

PMID- 25756075
TI  - Olfactory cleft opacity and CT score are predictive factors of smell recovery
      after surgery in nasal polyposis.
AB  - OBJECTIVES: To assess subjective improvement of olfactory function following
      endoscopic sinus surgery (ESS) in chronic rhinosinusitis associated with nasal
      polyps (CRSwNP) and to analyse factors of recovery with the European Test of
      Olfactory Capabilities (ETOC). METHODS: We carried out a prospective study of 30
      patients with CRSwNP from November 2011 to April 2013. The ETOC was filled the
      day before surgery and in the short term follow-up. Sixteen suprathreshold
      odorants with a detection task and a forced choice verbal identification task
      were tested. RESULTS: The mean composite score (MCS) improved at 3 and 6 months.
      The preoperative MCS was correlated to the Lund-Mackay score and to the olfactory
      cleft opacification on preoperative computed tomography (CT) scan. Multivariate
      linear regression modelling of patients with preoperative anosmia showed that the
      olfactory recovery at 3 months was predicted by the preoperative Lund-Mackay
      score and the age, and at 6 months by the preoperative Lund-Mackay score.
      CONCLUSION: With a convenient psychophysical test, we showed that olfactory cleft
      opacification and CT scan score could be predictive factors of olfaction disorder
      severity and improvement after ESS in CRSwNP. These results need to be
      strengthened in the long term with a larger panel of patients.

PMID- 25756076
TI  - Treatment outcomes of midfacial segment pain: experience from the Liverpool multi
      disciplinary team facial pain clinic.
AB  - OBJECTIVES: Midfacial segment pain (MSP) has the characteristics of tension-type
      headache which is confined to the midface cor- responding to the second division
      of the trigeminal nerve. This review presents treatment outcomes of MSP patients
      managed at the Multi-disciplinary Team (MDT) Facial Pain Clinic in Liverpool.
      METHODOLOGY: Prospective clinical outcome performed in a tertiary referral centre
      for complex facial pain syndromes. MAIN OUTCOME MEASURES: Sino-Nasal Outcome Test
      (SNOT). Clinical "success" was defined as an improvement in total SNOT score of
      >9 points and a reduction of the ear-facial symptoms sub-domain score by >=50%
      from baseline. RESULTS: The average age of the cohort was 49 years, with an
      average follow-up of 12 months. The overall pre-treatment total SNOT-22 score was
      59.5 which improved significantly to 42 at latest follow-up. Although the average
      scores of all sub-domains improved, only the ear-facial symptoms and
      psychological issues sub-domains achieved statistical significance. When the
      criterion for success was applied, nine patients fulfilled this definition at an
      average of 12 months follow-up. The baseline total SNOT score in this cohort
      improved from 60.6 to 19.7. Half of these patients achieved success within 18
      months of commencing treatment and the probability of attaining success at long
      term follow-up was high. CONCLUSIONS: Treatment of midfacial segment facial pain
      is complex and requires follow-up to achieve any meaningful clinical outcome.

PMID- 25756077
TI  - A computational study of functional endoscopic sinus surgery and maxillary sinus
      drug delivery.
AB  - BACKGROUND: Topical medication is increasingly used following functional
      endoscopic sinus surgery (FESS). Information on particle sizes that maximise
      maxillary sinus (MS) delivery is conflicting, and the effect of antrostomy size
      on delivery is unclear. The purpose of this study was to estimate antrostomy and
      particle size effects on topical MS drug delivery. METHODOLOGY: Sinonasal
      reconstructions were created from a pre- and a post-FESS CT scan in each of four
      chronic rhinosinusitis patients. Additional models were created from each post
      FESS reconstruction representing four alternative antrostomy sizes. Airflow and
      particle deposition were simulated in each reconstruction using computational
      fluid dynamics for nebulised and sprayed delivery. RESULTS: MS ventilation and
      drug delivery increased following FESS, the largest virtual antrostomy led to
      greatest delivery, and MS delivery was sensitive to particle size. Particles
      within a 5-18 MUm and 5-20 MUm size range led to peak MS deposition for nebulised
      and sprayed particles, respectively. Post-FESS increases in drug delivery varied
      across individuals and within individuals by the type of antrostomy created.
      CONCLUSION: Our findings suggest that FESS, particularly with larger
      antrostomies, improves topical drug delivery, and that certain particle sizes
      improve this delivery. Further research is needed to contextualise these findings
      with other post-surgical effects.

PMID- 25756078
TI  - Accuracy of a questionnaire for identifying respiratory allergies in
      epidemiological studies.
AB  - BACKGROUND: The assessment of allergic asthma (AA) and allergic rhinitis (AR) in
      epidemiological studies is often challenging. We performed a cross-sectional
      study to test the accuracy of a Questionnaire aimed at Identifying subjects with
      Respiratory Allergy (QIRA) in a simple and fast way. METHODS: One hundred-thirty
      subjects, 18-76 years of age, admitted consecutively at the Allergy Center of the
      Niguarda Ca' Granda Hospital of Milan were included. The questionnaire (index
      test) investigated the presence of AA and AR with seven questions enquiring
      history of symptoms, diagnosis made by a doctor, allergy tests performed, and
      treatments. After completing the questionnaire, all subjects were subsequently
      diagnosed by an allergist (reference standard). RESULTS: The accuracy of the
      questionnaire for the diagnosis of AA and AR was high (sensitivity 94.7% [95%
      confidence interval CI: 74.0-99.9] and specificity 99.1% [95% CI 95.1-100.0] for
      AA; sensitivity 82.8% [95% CI 71.3-91.1] and specificity 98.5% [95% CI 91.8
      100.0] for AR). CONCLUSION: The questionnaire significantly distinguished
      subjects with respiratory allergy from those without. The QIRA represents a valid
      and accurate tool for classifying subjects as having or not AA and/or AR in
      epidemiological studies.

PMID- 25756079
TI  - Quality of life after septorhinoplasty measured with the Functional Rhinoplasty
      Outcome Inventory 17 (FROI-17).
AB  - BACKGROUND: Quality of life measurements in septorhinoplasty patients so far have
      taken place only to a small extent. The aim of the present study was a
      prospective measurement of disease-specific quality of life with a newly
      developed and validated instrument, the Functional Rhinoplasty Outcome Inventory
      17 (FROI-17). METHODS: The patients completed the FROI-17 and the Rhinoplasty
      Outcome Evaluation (ROE) as disease-specific instruments preoperatively as well
      as 12 months postoperatively. As a general instrument, the Short Form 36 Health
      Survey (SF-36) was used. Furthermore, additional general questions were answered
      at both time points. RESULTS: Out of the 103 patients, 69 patients (32 men, 37
      women) responded after 12 months (response rate 67%). Thirteen patients (18%)
      were not satisfied with the result of surgery. However, all scales of FROI-17 and
      also ROE showed a significant postoperative improvement of subjective assessments
      by the patients. In the SF-36, this was true in 2 out of 8 scales (mental health
      and role-functioning physical). Furthermore, we found significant correlations
      between the FROI-17 and the SF-36 scales but not between the ROE and the SF-36
      scales. CONCLUSION: The disease-specific quality of life was significantly
      improved by septorhinoplasty. FROI-17 scales detect more functional aspects
      compared with the ROE thus establishing significant correlations with general
      quality of life measured by SF-36. The application of both FROI-17 and ROE in
      future clinical trials in septorhinoplasty patients is recommended.

PMID- 25756080
TI  - Septoplasty with concomitant inferior turbinate reduction reduces the need for
      revision procedure.
AB  - OBJECTIVE: Septoplasty is an accepted and common surgical intervention to improve
      the nasal airway. However, the role of concomitant surgery on the inferior
      turbinate remains debated. This study aims to investigate if the inferior
      turbinate surgery at the time of septoplasty would impact on the likelihood of
      revision nasal surgery - septoplasty or septorhinoplasty. STUDY DESIGN:
      Retrospective review of consecutive patients undergoing septoplasty with or
      without inferior turbinate reduction over 12 years (1998 - 2010) at Aberdeen
      Royal Infirmary. METHODS: Patients were identified from the theatre log books and
      were excluded if they underwent any other nasal procedure. Data collected include
      demographics, type of primary surgery, and grade of surgeon along with revision
      nasal surgery in this cohort. RESULTS: 2168 eligible patients with a mean age of
      39 years were investigated. Two groups were identified: Group A, with 788
      patients who underwent septoplasty only, and Group B, in which 1380 patients
      underwent septoplasty with concomitant inferior turbinate reduction. The majority
      of operations were performed by the surgeons in training. The incidence of
      revision surgery was 5.1 % (21 revision septoplasties and 19 corrective
      septorhinoplasties) in Group A compared to 2.2 % (20 revision septoplasties and
      10 corrective septorhinoplasties) in Group B. CONCLUSION: Based on this study, it
      would appear that concomitant inferior turbinate reduction may decrease the
      likelihood of revision nasal surgery.

PMID- 25756081
TI  - Comparison of acoustic rhinometry and nasal inspiratory peak flow as objective
      tools for nasal obstruction assessment in patients with chronic rhinosinusitis.
AB  - BACKGROUND: Chronic rhinosinusitis (CRS) is a disease with increasing incidence,
      characterized by persistent symptoms and negative impact on patient's quality of
      life. Nasal inspiratory peak flow (NIPF) and acoustic rhinometry (AR) were
      studied and compared as assessment tools for CRS with or without nasal polyps
      (NP), as well as, in follow up monitoring of conservative medical treatment.
      OBJECTIVES: Seventy-eight patients were prospectively studied. Objective
      assessment included NIPF and AR at baseline and at 4 and 8 weeks after onset
      medical treatment. Measurements were studied in correlation with Sinonasal
      Outcome Test-22 (SNOT-22) questionnaire, Visual Analogue Scale (VAS) and
      endoscopic appearance score (EAS). RESULTS: Both NIPF and AR improved
      significantly, after medical treatment. NIPF score reflected CRS symptoms'
      improvement according to SNOT-22 total score at the end of treatment protocol,
      showing moderate to strong correlation with nasal obstruction VAS grading during
      the treatment period. AR measures were associated with EAS in all sets of
      examinations and correlated moderately with VAS scoring at 8 weeks. CONCLUSION:
      NIPF and AR were proven to be promising methods for objective evaluation and
      monitoring of nasal obstruction based on different aspects of nasal physiology in
      patients with CRS.

PMID- 25756083
TI  - The natural history of community-acquired common colds symptoms assessed over 4
      years.
AB  - BACKGROUND: The common cold is the most frequently experienced infection among
      humans, but limited data exist to characterize the onset, duration, severity and
      intersection of symptoms in community-acquired colds. A more complete
      understanding of the symptom frequency and burden in naturally occurring colds is
      needed. METHODOLOGY: We characterized common cold symptoms from 226 cold episodes
      experienced by 104 male or female subjects. Subjects were enrolled in the work
      environment in an attempt to start symptom evaluation (frequency and severity) at
      the earliest sign of their cold. We also assessed the symptom that had the
      greatest impact on the subject by asking them to identify their single most
      bothersome symptom. RESULTS: Symptom reporting started within 24 hours of cold
      onset for most subjects. Sore throat was a harbinger of the illness but was
      accompanied by multiple symptoms, including nasal congestion, runny nose and
      headache. Cough was not usually the most frequent symptom, but was present
      throughout the cold, becoming most bothersome later in the cold. Nasal
      congestion, pain (eg, sore throat, headache, muscle pains) or feverishness and
      secretory symptoms (eg, runny nose, sneezing), and even cough, were
      simultaneously experienced with high incidence over the first 4 days of illness.
      The single most bothersome symptom was sore throat on day 1, followed by nasal
      congestion on days 2-5 and cough on days 6 and 7. CONCLUSION: There is
      substantial overlap in the appearance of common cold symptoms over the first
      several days of the common cold. Nasal congestion, secretory and pain symptoms
      frequently occur together, with cough being somewhat less prominent, but quite
      bothersome when present. These data establish the typical symptomatology of a
      common cold and provide a foundation for the rational treatment of cold symptoms
      typically experienced by cold sufferers.

PMID- 25756082
TI  - Sinonasal malignancies in Sweden 1960-2010; a nationwide study of the Swedish
      population.
AB  - INTRODUCTION: Sinonasal malignancies (SNM) are rare and the prognosis is
      generally poor. Recently, a change in incidence for SNM has been reported. In
      this study, we investigated population-based trends for SNM in Sweden. METHODS:
      We identified 3,221 patients from the Swedish National Cancer Registry diagnosed
      with primary malignancies arising from the nasal cavity, paranasal sinuses, or
      both, during the period 1960 through 2010. Incidence, gender and age, anatomical
      sites and relative survival were investigated. RESULTS: The incidence for SNM
      decreased except for sinonasal malignant melanoma (SNMM) and adenoid cystic
      cancer (even though a very small group) during the study period. More than 50 %
      of the malignancies involved the nasal cavity. The five-year relative survival
      was highest for adenoid cystic cancer followed by adenocarcinoma. SNMM and
      undifferentiated carcinoma had the poorest prognosis. CONCLUSION: We found that
      the incidence for SNM has decreased during the study period 1960 through 2010,
      except for SNMM that has increased.

PMID- 25756085
TI  - Facile synthesis of porous bimetallic alloyed PdAg nanoflowers supported on
      reduced graphene oxide for simultaneous detection of ascorbic acid, dopamine, and
      uric acid.
AB  - Porous bimetallic alloyed palladium silver (PdAg) nanoflowers supported on
      reduced graphene oxide (PdAg NFs/rGO) were prepared via a facile and simple in
      situ reduction process, with the assistance of cetyltrimethylammonium bromide as
      a structure directing agent. The as-prepared nanocomposite modified glassy carbon
      electrode (PdAg NFs/rGO/GCE) showed enhanced catalytic currents and enlarged peak
      potential separations for the oxidation of ascorbic acid (AA), dopamine (DA), and
      uric acid (UA) as compared to those of PdAg/GCE, rGO/GCE, commercial Pd/C/GCE,
      and bare GCE. The as-developed sensor can selectively detect AA, DA, and UA with
      a good anti-interference ability, wide concentration ranges of 1.0 MUM-2.1 mM,
      0.4-96.0 MUM, and 1.0-150.0 MUM, respectively, together with low detection limits
      of 0.057, 0.048, and 0.081 MUM (S/N = 3), respectively. For simultaneous
      detection of AA, DA, and UA, the linear current-concentration responses were
      observed from 1.0 MUM-4.1 mM, 0.05-112.0 MUM, and 3.0-186.0 MUM, with the
      detection limits of 0.185, 0.017, and 0.654 MUM (S/N = 3), respectively. 

PMID- 25756084
TI  - Even cognitively well-functioning adults are unaware of their olfactory
      dysfunction: Implications for ENT clinicians and researchers.
AB  - BACKGROUND: Past findings of an impact of cognitive impairment on awareness of
      olfactory dysfunction, and high prevalence of age-associated cognitive impairment
      motivated the present study of whether middle-aged and elderly adults are unaware
      of an olfactory dysfunction despite being carefully screened for cognitive
      impairment. METHODOLOGY: The sample included 203 Norwegian participants, aged 46
      79 years, 134 women and 69 men, who underwent comprehensive neuropsychological
      assessment for screening of cognitive impairment. Subjective assessment of
      olfactory function ("How would you estimate your sense of smell?") was compared
      with outcome on objective assessment of olfactory function with the Scandinavian
      Odor Identification Test, which in the present study was shown to be valid for
      use on Norwegian populations. RESULTS: We found that 79% of this cognitively
      healthy sample with objectively assessed olfactory dysfunction reported normal
      olfactory function (57% of functionally anosmics reported normal function). In
      contrast, only 9% with objectively assessed normal olfactory function reported
      olfactory dysfunction. CONCLUSION: A large proportion of cognitively well
      functioning middle-aged and elderly adults with an olfactory dysfunction are
      unaware of their dysfunction. The ENT physician who suspects that the sense of
      smell may be compromised should, in addition to an anamnesis, assess the
      patient's olfactory function objectively.

PMID- 25756086
TI  - A novel immobilization strategy for electrochemical detection of cancer
      biomarkers: DNA-directed immobilization of aptamer sensors for sensitive
      detection of prostate specific antigens.
AB  - We report on a novel strategy for DNA aptamer immobilization to develop sensitive
      electrochemical detection of a protein biomarker, with prostate specific antigen
      (PSA) as a case biomarker. Thiolated single-stranded DNA (ssDNA) was co
      immobilized with 3-mercapto-1-propanol on gold electrodes, and used as a scaffold
      for DNA aptamer attachment through hybridization of the aptamer overhang (so
      called "DNA-directed immobilization aptamer sensors", DDIAS). In the approach,
      the complementary DNA aptamer against PSA was assembled by the probe ssDNA onto
      the electrode to detect PSA; or the probe ssDNA directly hybridized with a
      complementary DNA aptamer/PSA complex following their pre-incubation in solution,
      so-called 'on-chip' and 'in-solution' methods, respectively. A double stranded
      DNA intercalator with a ferrocenyl (Fc) redox marker was synthesized to evaluate
      the feasibility of the strategy. The results demonstrate that the 'in-solution'
      method offers a favourable medium (in a homogeneous solution) for the binding
      between the aptamer and PSA, which shows to be more efficient than the 'on-chip'
      approach. DDIAS shows promising analytical performance under optimized
      conditions, with a limit of detection in the range of fM and low non-specific
      adsorption. 

PMID- 25756087
TI  - A highly efficient three-phase single drop microextraction technique for sample
      preconcentration.
AB  - A highly efficient three-phase single drop microextraction (SDME) method is
      presented by using an organic-aqueous compound droplet. A coupling microdevice is
      designed to produce compound droplets in different sizes conveniently. In this
      way, the volume ratio of organic phase to aqueous phase in a compound droplet can
      be significantly reduced. Good operability and droplet stability were observed
      during extraction under vigorous stirring conditions. Five statins were used as
      model compounds and spiked in river water and human serum samples to evaluate the
      analytical performance of the proposed method. By using a 1.2 MUL toluene-aqueous
      compound droplet (volume ratio 0.2 : 1), a 350 to 1712 fold enrichment of statins
      was obtained within 4 minutes. The results indicate that the proposed method is a
      very rapid and efficient sample pretreatment method, and is promising for
      automated and high-throughput applications. 

PMID- 25756088
TI  - Proceedings of the 1st International Symposium on Giant Virus Biology, November
      17-20, 2013, Ringberg Castle, Germany.

PMID- 25756089
TI  - Proceedings of the 18th Scientific Meeting of the Society of Hair Testing (SoHT),
      August 28-30, 2013, Geneva, Switzerland.

PMID- 25756090
TI  - Proceedings of the 16th EVSSAR Congress, 5-6 July 2013, Toulouse, France.

PMID- 25756091
TI  - Retraction notice to 'Corrigendum to "3-Benzhydryl-4-piperidones as novel
      neurokinin-1 receptor antagonists and their efficient synthesis"' [Bioorg. Med.
      Chem. 20 (2012) 5668-5668].

PMID- 25756092
TI  - Proceedings of The Joint International Symposium on EPR Dosimetry and Dating and
      the International Conference on Biological Dosimetry (EPR-BioDose 2013), March 24
      28, 2013, Leiden, The Netherlands.

PMID- 25756094
TI  - Abstracts of the 12th European Biological Inorganic Chemistry Conference, August
      24-28, 2014, Zurich, Switzerland.

PMID- 25756093
TI  - A special issue in memoriam of Carl Woese.

PMID- 25756095
TI  - Memorial Issue Dedicated to Francois Jacob.

PMID- 25756096
TI  - Special issue dedicated to Prof. Michael J. Dunn.

PMID- 25756097
TI  - [Position paper of the Chilean Academy of Medicine about relations between
      medical doctors and the industry provider on health topics].

PMID- 25756098
TI  - Ebola preparedness: on avoiding making a scary virus scarier.

PMID- 25756099
TI  - Channeling, high-level biocontainment and research.

PMID- 25756100
TI  - Gallows humor, fearmongering continue to spread.

PMID- 25756101
TI  - Updated estimates of fatality reduction by curtain and side air bags in side
      impacts and preliminary analyses of rollover curtains.

PMID- 25756102
TI  - Abstracts of the 2014 American Congress of Obstetricians and Gynecologists Annual
      Clinical Meeting (ACOG), April 28-May 1, 2014, Chicago, IL.

PMID- 25756103
TI  - Perceptions of D.M.D. student readiness for basic science courses in the United
      States: can online review modules help?
AB  - There can be a disconnect between the level of content covered in undergraduate
      coursework and the expectations of professional-level faculty of their incoming
      students. Some basic science faculty members may assume that students have a good
      knowledge base in the material and neglect to appropriately review, whilst others
      may spend too much class time reviewing basic material. It was hypothesised that
      the replacement of introductory didactic physiology lectures with interactive
      online modules could improve student preparedness prior to lectures. These
      modules would also allow faculty members to analyse incoming student abilities
      and save valuable face-to-face class time for alternative teaching strategies.
      Results indicated that the performance levels of incoming U.S. students were poor
      (57% average on a pre-test), and students often under-predicted their abilities
      (by 13% on average). Faculty expectations varied greatly between the different
      content areas and did not appear to correlate with the actual student
      performance. Three review modules were created which produced a statistically
      significant increase in post-test scores (46% increase, P < 0.0001, n = 114-115).
      The positive results of this study suggest a need to incorporate online review
      units in the basic science dental school courses and revise introductory material
      tailored to students' strengths and needs.

PMID- 25756104
TI  - Students' perception of peer-assessment in the context of a  treatment planning
      course.
AB  - OBJECTIVE: Peer assessment is grounded in philosophies of active learning, and it
      would seem that this tool is a viable method for critical thinking development.
      The purpose of this article was to present how junior students at Case Western
      Reserve University School of Dental Medicine (CWRU) perceive the value of a peer
      assessment activity in the context of a treatment planning course. METHODOLOGY:
      As a part of the final exam for the junior year Treatment Planning course,
      students were requested to evaluate a de-identified assignment submitted by one
      of their peers. Following the exam, a survey was sent to the students to
      determine how they perceived the peer-assessment activity and how this relates to
      other learning experiences in the course. RESULTS: Our results show that
      students' perception of the benefit of peer grading was not associated with any
      individual peer-assignment characteristics, or course characteristics. Similar
      results were obtained regarding the perceived benefit of identifying evidence.
      Moderate correlations were observed between peer evaluation characteristics.
      CONCLUSIONS: It was concluded that: (i) junior dental students are not homogenous
      in their opinions regarding the value of an activity related to evaluation of a
      peer's assignment and (ii) student's perceptions regarding the peer-grading
      component of peer assessment were not correlated with perceptions related to
      other learning processes in the treatment planning course.

PMID- 25756105
TI  - Certificationizing continuing education.

PMID- 25756106
TI  - Gram-negative bacteria can also form pellicles.
AB  - There is a growing interest in the bacterial pellicle, a biofilm floating at the
      air-liquid interface. Pellicles have been well studied in the Gram-positive
      bacterium Bacillus subtilis, but far less in Gram-negative bacteria, where
      pellicle studies have mostly focused on matrix components rather than on the
      regulatory cascades involved. Several Gram-negative bacteria, including
      pathogenic bacteria, have been shown to be able to form a pellicle under static
      conditions. Here, we summarize the growing body of knowledge about pellicle
      formation in Gram-negative bacteria, especially about the components of the
      pellicle matrix. We also propose that the pellicle is a specific biofilm, and
      that its formation involves particular processes. Since this lifestyle concerns a
      growing number of bacteria, its properties undoubtedly deserve further
      investigation.

PMID- 25756107
TI  - Bacterial responses to antibiotics and their combinations.
AB  - Antibiotics affect bacterial cell physiology at many levels. Rather than just
      compensating for the direct cellular defects caused by the drug, bacteria respond
      to antibiotics by changing their morphology, macromolecular composition,
      metabolism, gene expression and possibly even their mutation rate. Inevitably,
      these processes affect each other, resulting in a complex response with changes
      in the expression of numerous genes. Genome-wide approaches can thus help in
      gaining a comprehensive understanding of bacterial responses to antibiotics. In
      addition, a combination of experimental and theoretical approaches is needed for
      identifying general principles that underlie these responses. Here, we review
      recent progress in our understanding of bacterial responses to antibiotics and
      their combinations, focusing on effects at the levels of growth rate and gene
      expression. We concentrate on studies performed in controlled laboratory
      conditions, which combine promising experimental techniques with quantitative
      data analysis and mathematical modeling. While these basic research approaches
      are not immediately applicable in the clinic, uncovering the principles and
      mechanisms underlying bacterial responses to antibiotics may, in the long term,
      contribute to the development of new treatment strategies to cope with and
      prevent the rise of resistant pathogenic bacteria.

PMID- 25756108
TI  - Control of sulfidogenesis through bio-oxidation of H2S coupled to (per)chlorate
      reduction.
AB  - We investigated H2S attenuation by dissimilatory perchlorate-reducing bacteria
      (DPRB). All DPRB tested oxidized H2S coupled to (per)chlorate reduction without
      sustaining growth. H2S was preferentially utilized over organic electron donors
      resulting in an enriched (34S)-elemental sulfur product. Electron microscopy
      revealed elemental sulfur production in the cytoplasm and on the cell surface of
      the DPRB Azospira suillum. Based on our results, we propose a novel hybrid
      enzymatic-abiotic mechanism for H2S oxidation similar to that recently proposed
      for nitrate-dependent Fe(II) oxidation. The results of this study have
      implications for the control of biosouring and biocorrosion in a range of
      industrial environments.

PMID- 25756109
TI  - Nitrospina-like bacteria are the main drivers of nitrite oxidation in the
      seasonal upwelling area of the Eastern South Pacific (Central Chile ~36 degrees
      S).
AB  - Aerobic nitrite oxidation in marine environments plays a key role in the
      nitrification process. Marine bacteria involved in this nitrate-producing process
      have however been seldom studied compared with the ammonia-oxidizing community.
      Here, we report for the first time the community structure of aerobic nitrite
      oxidizing bacteria (NOB) in the seasonal upwelling and oxygen-deficient area off
      Central Chile. Analysis of 16S rRNA by tag pyrosequencing was combined with
      specific quantitative polymerase chain reaction (qPCR) and reverse transcription
      qPCR in summer and wintertime. Nitrospina-like bacteria were the only known NOB
      detected by means of pyrosequencing between 30 and 80 m depth, accounting for up
      to 5% of total bacteria. This guild was represented by 11 and 7 operational
      taxonomic units (97% cut-off) in winter and summertime respectively. Nitrospina
      like bacteria were phylogenetically related to sequences retrieved from coastal
      upwelling, oxygen minimum zones and deep-sea environments. This group was also
      detected by qPCR with abundances that increased with depth throughout the water
      column. Importantly, Nitrospina from surface layers showed low abundances but
      high 16S rRNA : rDNA ratios and mainly in summertime. Overall, our results
      highlight the seasonal variability between the structure and physiological state
      of this community and suggest a significant role of Nitrospina in the nitrogen
      cycle of seasonal upwelling areas.

PMID- 25756110
TI  - Marine bacterial communities are resistant to elevated carbon dioxide levels.
AB  - It is well established that the release of anthropogenic-derived CO2 into the
      atmosphere will be mainly absorbed by the oceans, with a concomitant drop in pH,
      a process termed ocean acidification. As such, there is considerable interest in
      how changes in increased CO2 and lower pH will affect marine biota, such as
      bacteria, which play central roles in oceanic biogeochemical processes. Set
      within an ecological framework, we investigated the direct effects of elevated
      CO2, contrasted with ambient conditions on the resistance and resilience of
      marine bacterial communities in a replicated temporal seawater mesocosm
      experiment. The results of the study strongly indicate that marine bacterial
      communities are highly resistant to the elevated CO2 and lower pH conditions
      imposed, as demonstrated from measures of turnover using taxa-time relationships
      and distance-decay relationships. In addition, no significant differences in
      community abundance, structure or composition were observed. Our results suggest
      that there are no direct effects on marine bacterial communities and that the
      bacterial fraction of microbial plankton holds enough flexibility and
      evolutionary capacity to withstand predicted future changes from elevated CO2 and
      subsequent ocean acidification.

PMID- 25756111
TI  - Diversity and genome dynamics of marine cyanophages using metagenomic analyses.
AB  - Cyanophages are abundant in the oceanic environment and directly impact
      cyanobacterial distributions, physiological processes and evolution. Two samples
      collected from coastal Maine in July and September 2009 were enriched for
      Synechococcus cells using flow cytometry and examined through metagenomic
      sequencing. Homology-based sequence prediction indicated cyanophages, largely
      myoviruses, accounted for almost half the reads and provided insights into
      environmental infection events. T4-phage core-gene phylogenetic reconstruction
      revealed unique diversity among uncultured cyanophages and reference isolates
      resulting in identification of a new phylogenetic cluster. Genomic comparison of
      reference cyanophage strains S-SM2 and Syn1 with putative homologous contigs
      recovered from metagenomes provided evidence that gene insertion, deletion and
      recombination have occurred among, and are likely important for diversification
      of, natural populations. Identification of putative genetic exchange between
      cyanophage and non-cyanophage viruses, i.e. Micromonas virus and Pelagibacter
      phage, supports hypotheses related to a significant role for viruses in mediating
      transfer of genetic material between taxonomically diverse organisms with
      overlapping ecological niches.

PMID- 25756112
TI  - The first report of a microdiverse anammox bacteria community in waters of
      Colombian Pacific, a transition area between prominent oxygen minimum zones of
      the eastern tropical Pacific.
AB  - Anaerobic ammonium oxidizers contribute to the removal of fixed nitrogen in
      oxygen-deficient marine ecosystems such as oxygen minimum zones (OMZ). Here we
      surveyed for the first time the occurrence and diversity of anammox bacteria in
      the Colombian Pacific, a transition area between the prominent South and North
      Pacific OMZs. Anammox bacteria were detected in the coastal and oceanic areas of
      the Colombian Pacific in low oxygen (< 22 MUM), high nitrate (25-35 MUM) and low
      nitrite (< 0.07 MUM), and ammonium (< 1 MUM) waters. In these waters, anammox
      bacteria were rich [~ 7 operational taxonomic units (OTUs), 98% cut-off) and
      microdiverse (Shannon index H' < 1.24), in comparison with the observed at the
      prominent OMZ of the Eastern Tropical South Pacific, Arabian Sea and Black Sea.
      Anammox bacteria-like sequences from the Colombian Pacific were grouped together
      with sequences retrieved from the distinct OMZ's marine subclusters (Peru,
      Northern Chile and Arabian Sea) within Candidatus 'Scalindua spp'. Moreover, some
      anammox bacteria OTUs shared a low similarity with environmental phylotypes (86
      94%). Our results indicated that a microdiverse anammox community inhabits the
      Colombian Pacific, generating new questions about the ecological and
      biogeochemical differences influencing its community structure.

PMID- 25756113
TI  - Sex-dependent competitive dominance of phylogenetic group B2 Escherichia coli
      strains within human hosts.
AB  - Escherichia coli can be divided into several distinct phylogenetic groups that
      differ in their capacity to cause disease. However, what drives the relative
      abundance of these different phylogenetic groups in the commensal intestinal
      community of humans is poorly understood. This study investigated how host age
      and sex influences E. coli community structure in humans. Faecal samples were
      collected from 205 outpatients in Australia. Different strains within each sample
      were identified using rep-PCR profiles and their phylogenetic group membership
      was determined by quadruplex PCR. Female individuals carrying a dominant B2
      strain were found to possess fewer strains than those carrying dominant A or B1
      strains. Additionally, strains from the same phylogenetic group were more likely
      to co-occur in females. By contrast, strain diversity and phylogenetic group
      associations did not differ significantly from random in males. Host age was
      found to have a significant effect on the phylogenetic group of the dominant
      strain. Together these findings indicate that the distribution of the different
      phylogenetic groups within the human intestinal tract may be mediated by a
      complex interaction between the host environment and the competitive interactions
      between strains.

PMID- 25756114
TI  - Fluorescence in situ hybridization probes targeting members of the phylum
      Candidatus Saccharibacteria falsely target Eikelboom type 1851 filaments and
      other Chloroflexi members.
AB  - The FISH probe TM7-305 is thought to target the filamentous Eikelboom morphotype
      0041 as a member of the Candidatus 'Saccharibacteria' (formerly TM7) phylum.
      However, with activated sludge samples in both Japan and Australia, this probe
      hybridized consistently with filamentous bacteria fitting the description of the
      morphotype 1851, which also responded positively to the CHL1851 FISH probe
      designed to target Chloroflexi members of this morphotype. 16S rRNA clone
      libraries from samples containing type 1851 TM7-305-positive filaments yielded
      Chloroflexi clones with high sequence similarity to Kouleothrix aurantiaca. These
      contained a variant TM7-305 probe target site possessing weakly destabilizing
      mismatches insufficient to prevent probe hybridization. Furthermore, the TM7-905
      FISH probe, designed to target members of the entire Candidatus
      'Saccharibacteria' phylum, also hybridized with the filament morphotypes
      0041/0675, which responded also to the phylum level Chloroflexi probes. Many
      Chloroflexi sequences have only a single base mismatch to the TM7-905 probe
      target sequence. When competitor probes for both the TM7-305 and TM7-905
      Chloroflexi non-target sites were applied, no fluorescent signal was seen in any
      of the filamentous organisms also hybridizing with the aforementioned Chloroflexi
      probes. These data indicate that these competitor probes must be included in
      hybridizations when both the TM7-905 and TM7-305 FISH probes are applied, to
      minimize potential false positive FISH results.

PMID- 25756116
TI  - Distribution of the verrucomicrobial clade Spartobacteria along a salinity
      gradient in the Baltic Sea.
AB  - A recent pyrosequencing study along the whole Baltic Sea salinity transect
      identified members of the Verrucomicrobia class Spartobacteria as an important
      component of Baltic Sea bacterioplankton. In this study, catalysed reporter
      deposition-fluorescence in situ hybridization was used for cellular
      quantification. The published probes VER47 and SPA714 were optimized for samples
      from the Baltic Sea and a new, specific probe (SPA476) was used to quantify the
      dominant spartobacterial lineage 'LD29'. The results confirmed that in the
      brackish surface waters of the Baltic Sea Spartobacteria comprise an important
      component, constituting up to 12% of all bacteria. The positive correlation and
      physical association of Spartobacteria with phytoplankton suggest their
      involvement in the utilization of phytoplankton-derived organic matter in the
      Baltic Sea.

PMID- 25756115
TI  - Bacterial diversity and composition during rain events with and without Saharan
      dust influence reaching a high mountain lake in the Alps.
AB  - The diversity of airborne microorganisms that potentially reach aquatic
      ecosystems during rain events is poorly explored. Here, we used a culture
      independent approach to characterize bacterial assemblages during rain events
      with and without Saharan dust influence arriving to a high mountain lake in the
      Austrian Alps. Bacterial assemblage composition differed significantly between
      samples with and without Saharan dust influence. Although alpha diversity indices
      were within the same range in both sample categories, rain events with Atlantic
      or continental origins were dominated by Betaproteobacteria, whereas those with
      Saharan dust intrusions were dominated by Gammaproteobacteria. The high diversity
      and evenness observed in all samples suggests that different sources of bacteria
      contributed to the airborne assemblage collected at the lake shore. During
      experiments with bacterial assemblages collected during rain events with Saharan
      dust influence, cell numbers rapidly increased in sterile lake water from
      initially ~3 * 103 cell ml-1 to 3.6-11.1 x105 cells ml-1 within 4-5 days, and
      initially, rare taxa dominated at the end of the experiment. Our study documents
      the dispersal of viable bacteria associated to Saharan dust intrusions travelling
      northwards as far as 47 degrees  latitude.

PMID- 25756117
TI  - Endospore-enriched sequencing approach reveals unprecedented diversity of
      Firmicutes in sediments.
AB  - We present a method for the physical isolation of endospores from environmental
      samples allowing the specific targeting of endospore-forming bacteria for
      sequencing (endospore-enriched community). The efficiency of the method was
      tested on lake sediment samples. After 16S rRNA gene amplicon sequencing, the
      composition in the endospore-enriched community was compared with the community
      from untreated control samples (whole community). In the whole community,
      Firmicutes had a relative abundance of 8% and 19% in the two different lake
      sediments. In contrast, in the endospore-enriched community, Firmicutes abundance
      increased to 90.6% and 83.9%, respectively, confirming the efficiency of the
      endospore enrichment. The relative abundance of other microbial groups that form
      spore-like resisting states (i.e. actinobacteria, cyanobacteria and myxococcales)
      was below 2% in the endospore-enriched community, indicating that the method is
      adapted to true endospores. Representatives from two out of the three known
      classes of Firmicutes (Bacilli and Clostridia) were detected and supposedly
      asporogenic groups (e.g. Ethanoligenes and Trichococcus) could be detected. The
      method presented here is a leap forward for ecological studies of endospore
      forming Firmicutes. It can be applied to other types of samples in order to
      reveal the diversity and metabolic potential of this bacterial group in the
      environment.

PMID- 25756118
TI  - Evaluation of metatranscriptomic protocols and application to the study of
      freshwater microbial communities.
AB  - Metatranscriptomics of environmental samples enables the identification of
      community activities without a priori knowledge of taxonomic or functional
      composition. However, several technical challenges associated with the RNA
      preparation protocols can affect the relative representation of transcripts and
      data interpretation. Here, seven replicate metatranscriptomes from planktonic
      freshwater samples (Lake Lanier, USA) were sequenced to evaluate technical and
      biological reproducibility of different RNA extraction protocols. Organic versus
      bead-beating extraction showed significant enrichment for low versus high G + C%
      mRNA populations respectively. The sequencing data were best modelled by a
      negative binomial distribution to account for the large technical and biological
      variation observed. Despite the variation, the transcriptional activities of
      populations that persisted in year-round metagenomes from the same site
      consistently showed distinct expression patterns, reflecting different ecologic
      strategies and allowing us to test prevailing models on the contribution of both
      rare biosphere and abundant members to community activity. For instance, abundant
      members of the Verrucomicrobia phylum systematically showed low transcriptional
      activity compared with other abundant taxa. Our results provide a practical guide
      to the analysis of metatranscriptomes and advance understanding of the activity
      and ecology of abundant and rare members of temperate freshwater microbial
      communities.

PMID- 25756119
TI  - Intracellular Oceanospirillales inhabit the gills of the hydrothermal vent snail
      Alviniconcha with chemosynthetic, gamma-Proteobacterial symbionts.
AB  - Associations between bacteria from the gamma-Proteobacterial order
      Oceanospirillales and marine invertebrates are quite common. Members of the
      Oceanospirillales exhibit a diversity of interactions with their various hosts,
      ranging from the catabolism of complex compounds that benefit host growth to
      attacking and bursting host nuclei. Here, we describe the association between a
      novel Oceanospirillales phylotype and the hydrothermal vent snail Alviniconcha.
      Alviniconcha typically harbour chemoautotrophic gamma- or epsilon-Proteobacterial
      symbionts inside their gill cells. Via fluorescence in situ hybridization and
      transmission electron microscopy, we observed an Oceanospirillales phylotype
      (named AOP for 'Alviniconcha Oceanospirillales phylotype') in membrane-bound
      vacuoles that were separate from the known gamma- or epsilon-Proteobacterial
      symbionts. Using quantitative polymerase chain reaction, we surveyed 181
      Alviniconcha hosting gamma-Proteobacterial symbionts and 102 hosting epsilon
      Proteobacterial symbionts, and found that the population size of AOP was always
      minor relative to the canonical symbionts (median 0.53% of the total quantified
      16S rRNA genes). Additionally, we detected AOP more frequently in Alviniconcha
      hosting gamma-Proteobacterial symbionts than in those hosting epsilon
      Proteobacterial symbionts (96% and 5% of individuals respectively). The high
      incidence of AOP in gamma-Proteobacteria hosting Alviniconcha implies that it
      could play a significant ecological role either as a host parasite or as an
      additional symbiont with unknown physiological capacities.

PMID- 25756120
TI  - Spatial distribution of microbial communities in the shallow submarine alkaline
      hydrothermal field of the Prony Bay, New Caledonia.
AB  - The shallow submarine hydrothermal field of the Prony Bay (New Caledonia)
      discharges hydrogen- and methane-rich fluids with low salinity, temperature (< 40
      degrees C) and high pH (11) produced by the serpentinization reactions of the
      ultramafic basement into the lagoon seawater. They are responsible for the
      formation of carbonate chimneys at the lagoon seafloor. Capillary electrophoresis
      single-strand conformation polymorphism fingerprinting, quantitative polymerase
      chain reaction and sequence analysis of 16S rRNA genes revealed changes in
      microbial community structure, abundance and diversity depending on the location,
      water depth, and structure of the carbonate chimneys. The low archaeal diversity
      was dominated by few uncultured Methanosarcinales similar to those found in other
      serpentinization-driven submarine and subterrestrial ecosystems (e.g. Lost City,
      The Cedars). The most abundant and diverse bacterial communities were mainly
      composed of Chloroflexi, Deinococcus-Thermus, Firmicutes and Proteobacteria.
      Functional gene analysis revealed similar abundance and diversity of both
      Methanosarcinales methanoarchaea, and Desulfovibrionales and Desulfobacterales
      sulfate-reducers in the studied sites. Molecular studies suggest that redox
      reactions involving hydrogen, methane and sulfur compounds (e.g. sulfate) are the
      energy driving forces of the microbial communities inhabiting the Prony
      hydrothermal system.

PMID- 25756122
TI  - Metaproteomics reveals the major microbial players and their biogeochemical
      functions in a productive coastal system in the northern South China Sea.
AB  - We study the metaproteome of the GF/F-prefiltered fraction of a microbial
      community from Shantou coast summer surface waters using a shotgun proteomic
      approach. Spectra attributed to the marine Roseobacter clade (MRC), the
      oligotrophic marine Gammaproteobacteria (OMG) group and Flavobacteria dominated
      in the microbial community, accounting for 21.0%, 23.2% and 12.7% of all of the
      detected spectra, respectively, whereas the SAR 92 clade accounted for 50% of the
      OMG group. The abundance of TonB-dependent receptors (TBDRs) was detected and the
      majority of TBDRs were attributed to the OMG, whereas a large number of ABC
      transporters matched to the MRC, which suggests niche separation in the microbial
      community. Expression of proteorhodopsin and RagB/SusD from Flavobacteria
      facilitates their attachment and growth on algal-derived organic matter. Taurine
      and glycine betaine appear to be an important source of carbon and nitrogen for
      the Rhodobacteraceae and SAR11 cluster. The detection of carbon monoxide
      dehydrogenase, formate dehydrogenase, O-acetylhomoserine sulfhydrylase and sulfur
      oxidation protein from the MRC demonstrated that members of the MRC play
      important roles in coastal ocean biogeochemical cycles. This study provides the
      first insight into functional processes occurring in microbial communities in
      coastal waters in the South China Sea.

PMID- 25756121
TI  - High occurrence of viruses in the mucus layer of scleractinian corals.
AB  - Viruses attract increasing interest from environmental microbiologists seeking to
      understand their function and role in coral health. However, little is known
      about their main ecological traits within the coral holobiont. In this study, a
      quantitative and qualitative characterization of viral and bacterial communities
      was conducted on the mucus of seven different coral species of the Van Phong Bay
      (Vietnam). On average, the concentrations of viruses and bacteria were,
      respectively, 17- and twofold higher in the mucus than in the surrounding water.
      The examination of bacterial community composition also showed remarkable
      differences between mucus and water samples. The percentage of active respiring
      cells was nearly threefold higher in mucus (m = 24.8%) than in water (m = 8.6%).
      Interestingly, a positive and highly significant correlation was observed between
      the proportion of active cells and viral abundance in the mucus, suggesting that
      the metabolism of the bacterial associates is probably a strong determinant of
      the distribution of viruses within the coral holobiont. Overall, coral mucus,
      given its unique physicochemical characteristics and sticking properties, can be
      regarded as a highly selective biotope for abundant, diversified and specialized
      symbiotic microbial and viral organisms.

PMID- 25756123
TI  - Detection of mecC-Methicillin-resistant Staphylococcus aureus isolates in river
      water: a potential role for water in the environmental dissemination.
AB  - Methicillin-resistant Staphylococcus aureus (MRSA) is a public health concern due
      to limited treatment options. The recent description of a mecA homologue, mecC in
      human and cattle, led to studies to detect this new variant in human and other
      animal species. Detection of mecC in wild boar and fallow deer in a Spanish game
      estate led us to further investigate the presence of mecC-MRSA at this location.
      Samples from cattle, wild animals, workers and river water were tested. A further
      three mecC-MRSA isolates were obtained from river water. Molecular
      characterization (multilocus sequence typing and spa typing) and antimicrobial
      susceptibility testing (broth microdilution) showed that isolates were similar to
      those detected in wild animals. Whole genome sequencing confirmed that the
      isolates from the river water and wild animals in the same geographic area were
      all closely related isolates of ST425 mecC-MRSA. The presence of mecC-MRSA in the
      river water highlights the potential role of water in the dissemination of mecC
      MRSA.

PMID- 25756125
TI  - Geobacter sp. SD-1 with enhanced electrochemical activity in high-salt
      concentration solutions.
AB  - An isolate, designated strain SD-1, was obtained from a biofilm dominated by
      Geobacter sulfurreducens in a microbial fuel cell. The electrochemical activity
      of strain SD-1 was compared with type strains, G. sulfurreducens PCA and
      Geobacter metallireducens GS-15, and a mixed culture in microbial electrolysis
      cells. SD-1 produced a maximum current density of 290 +/- 29 A m-3 in a high
      concentration phosphate buffer solution (PBS-H, 200 mM). This current density was
      significantly higher than that produced by the mixed culture (189 +/- 44 A m-3)
      or the type strains (< 70 A m-3). In a highly saline water (SW; 50 mM PBS and 650
      mM NaCl), current by SD-1 (158 +/- 4 A m-3) was reduced by 28% compared with 50
      mM PBS (220 +/- 4 A m-3), but it was still higher than that of the mixed culture
      (147 +/- 19 A m-3), and strains PCA and GS-15 did not produce any current.
      Electrochemical tests showed that the improved performance of SD-1 was due to its
      lower charge transfer resistance and more negative potentials produced at higher
      current densities. These results show that the electrochemical activity of SD-1
      was significantly different than other Geobacter strains and mixed cultures in
      terms of its salt tolerance.

PMID- 25756124
TI  - Heterotrophic bicarbonate assimilation is the main process of de novo organic
      carbon synthesis in hadal zone of the Hellenic Trench, the deepest part of
      Mediterranean Sea.
AB  - Ammonium-oxidizing chemoautotrophic members of Thaumarchaea are proposed to be
      the key players in the assimilation of bicarbonate in the dark (ABD). However,
      this process may also involve heterotrophic metabolic pathways, such as fixation
      of carbon dioxide (CO2) via various anaplerotic reactions. We collected samples
      from the depth of 4900 m at the Matapan-Vavilov Deep (MVD) station (Hellenic
      Trench, Eastern Mediterranean) and used the multiphasic approach to study the ABD
      mediators in this deep-sea ecosystem. At this depth, our analysis indicated the
      occurrence of actively CO2-fixing heterotrophic microbial assemblages dominated
      by Gammaproteobacteria with virtually no Thaumarchaea present. [14C]-bicarbonate
      incorporation experiments combined with shotgun [14C]-proteomic analysis
      identified a series of proteins of gammaproteobacterial origin. More than quarter
      of them were closely related with Alteromonas macleodii 'deep ecotype' AltDE, the
      predominant organism in the microbial community of MVD. The present study
      demonstrated that in the aphotic/hadal zone of the Mediterranean Sea, the
      assimilation of bicarbonate is associated with both chemolithoauto- and
      heterotrophic ABD. In some deep-sea areas, the latter may predominantly
      contribute to the de novo synthesis of organic carbon which points at the
      important and yet underestimated role heterotrophic bacterial populations can
      play the in global carbon cycle/sink in the ocean interior.

PMID- 25756126
TI  - Extended longevity and robust early-stage development of Caenorhabditis elegans
      by a soil microbe, Lysinibacillus sphaericus.
AB  - Caenorhabditis elegans, originally isolated from soil, is a nematode used in
      various fields of biological research including host-microbe interaction. While
      bacterial pathogens responsible for human infections have been actively studied
      in C. elegans, very few bacterial species that provide beneficial effects on C.
      elegans have been reported. Here, we tested several bacterial soil isolates and
      then characterized the effects of Lysinibacillus sphaericus on C. elegans growth
      related phenotypes. Worms fed with L. sphaericus lived significantly longer than
      those growing with typical Escherichia coli OP50. Early- and juvenile-stage
      growth was also highly stimulated by L. sphaericus; body size at 28 h post
      hatching was > 2 times larger than OP50-fed worms and L. sphaericus-fed worms
      moved through the larval stage development more rapidly than control worms. In
      addition, significantly elevated fertilization was observed in worms fed with L.
      sphaericus (~ 8 h faster than the control group). Furthermore, growth with L.
      sphaericus resulted in the production of larger numbers of progeny than the
      control growth with OP50. Worms grown with L. sphaericus were highly resistant to
      oxidative, osmotic and infection stresses. Together, our results reveal a novel
      mode of growth that involves healthy ageing of nematodes.

PMID- 25756127
TI  - Dr Karel Lewit 1916-2014.

PMID- 25756128
TI  - Why did evolution give us allergies?
AB  - The questions of why allergies exist and why they are becoming more prevalent
      continue to puzzle immunologists. Recent research has uncovered a wealth of
      details and in the process grown an impenetrable hedge of acronyms around the
      issue, but the answers may be hidden elsewhere, in the ecology and evolution of
      our interactions with insects, worms and snakes. Michael Gross reports.

PMID- 25756129
TI  - Thomas Suddendorf.

PMID- 25756130
TI  - [For and against: psychotherapeutical treatment of mild depression].

PMID- 25756131
TI  - [Karl Jaspers. 100 years "Allgemeine Psychopathologie". Reply].

PMID- 25756132
TI  - [The language of the psychiatrist as a complementary symbolism].

PMID- 25756133
TI  - Proton therapy websites: information anarchy creates confusion.

PMID- 25756134
TI  - Avoiding obsolescence in advanced prostate  cancer management: a guide for
      urologists.
AB  - Prostate cancer is one of the most common cancers diagnosed in men in the USA and
      20-30% of men treated for localised prostate cancer will fail therapy and develop
      advanced prostate cancer. More drugs have been approved for the treatment of
      advanced prostate cancer in the past 3 years than in the past three decades, and
      each drug has its own mechanism of action and, often, unique monitoring
      requirements. As the treatment landscape for men with advanced prostate cancer is
      undergoing significant expansion, the roles of both oncologists and urologists
      are shifting, and the decision for the urologist to treat vs refer requires early
      assessment to identify which patients are candidates for these novel treatments
      and the monitoring of patients for tolerability, response, and potential side
      effects. Given these rapid changes, the authors of this review met in January
      2013 and again in April 2013 to discuss the current challenges facing urologists
      in adopting these new treatments into their own practices. Here, we provide a
      brief overview of advanced prostate cancer medical therapies approved in the past
      decade, the necessary monitoring procedures and early detection methods needed to
      safely and effectively manage patients receiving these therapies, and our
      recommendations for applying these new therapies within different models of
      urology practice, such that urologists can remain an integral component of their
      patient's care once he has transitioned into advanced prostate cancer

PMID- 25756135
TI  - Venous thromboembolism (VTE) prophylaxis   and urological pelvic cancer surgery:
      a UK   national audit.
AB  - OBJECTIVES: To evaluate the use of post-discharge venous thromboembolism (VTE)
      prophylaxis in UK pelvic cancer centres consistent with national guidelines.
      METHODS: Data was collected from healthcare professionals from 64 UK pelvic
      cancer centres. RESULTS: After radical cystectomy (RC), all cancer centres
      routinely use low-molecular-weight heparin (LMWH) in the perioperative period.
      After RC 67% of cancer centres use post-discharge LMWH routinely. After radical
      prostatectomy (RP), 98% of units use perioperative LMWH VTE prophylaxis
      routinely. After RP, 61% of hospitals always use post-discharge LMWH. In all, 27%
      of all UK cancer centres reported deaths or serious VTE complications from
      urological pelvic cancer surgery in the last 2 years. CONCLUSIONS: The National
      Institute for Health and Care Excellence (NICE) issued explicit guidance of VTE
      prophylaxis after pelvic and abdominal cancer surgery. Conversion of national
      guidance into local policy is ~60% for UK pelvic cancer centres. A lack of good
      quality evidence is cited as a reason for not adhering to NICE guidance.

PMID- 25756136
TI  - Oncological predictive value of the 2004 World  Health Organisation grading
      classification in  primary T1 non-muscle-invasive bladder cancer.  A step forward
      or back?
AB  - OBJECTIVE: To compare the clinical reliability of the 1973 and 2004 World Health
      Organisation (WHO) classification systems in pT1 bladder cancer. PATIENTS AND
      METHODS: We retrospectively evaluated 291 consecutive patients who had pT1 high
      grade bladder cancer between 2004 and 2011. All tumours were simultaneously
      evaluated by a single uro-pathologist as high grade and G2 or G3. All patients
      underwent a second transurethral resection (TUR) and those confirmed with non
      muscle-invasive bladder cancer at second TUR received bacille Calmette-Guerin.
      Follow-up included urine cytology and cystoscopy 3 months after second TUR and
      then every 6 months for 5 years. Univariate and multivariate analysis to
      determine recurrence-free survival (RFS) and progression-free survival (PFS)
      rates were performed using the Kaplan-Meier method with the log-rank test.
      RESULTS: G2 tumours were found in 124 (46.6%) and G3 in 142 (53.4%) patients. The
      mean (median; range) follow-up period was 31.1 (19; 1-93) months. The 5-year RFS
      rate was 39.1% for the overall high grade population, and 49.1 and 31.8% for G2
      and G3 subgroups, respectively. The 5-year PFS was 82% for the overall high grade
      population and 89 and 73% for G2 and G3 subgroups, respectively. RFS (P < 0.002)
      and PFS (P < 0.001) rates were significantly different between the G2 and G3
      subgroups. In multivariate analysis, only the grade assessed according to the
      1973 WHO significantly correlated with both RFS (P = 0.003) and PFS (P < 0.001).
      CONCLUSION: The results suggest that the 1973 WHO classification system has
      higher prognostic reliability for patients with T1 disease. If confirmed, these
      findings should be carefully taken into account when making treatment decisions
      for patients with T1 bladder cancer.

PMID- 25756137
TI  - An assessment of the physical impact of complex  surgical tasks on surgeon errors
      and discomfort:  a comparison between robot-assisted,  laparoscopic and open
      approaches.
AB  - OBJECTIVES: To evaluate, in a simulated suturing task, individual surgeons'
      performance using three surgical approaches: open, laparoscopic and robot
      assisted. subjects and methods: Six urological surgeons made an in vitro
      simulated vesico-urethral anastomosis. All surgeons performed the simulated
      suturing task using all three surgical approaches (open, laparoscopic and robot
      assisted). The time taken to perform each task was recorded. Participants were
      evaluated for perceived discomfort using the self-reporting Borg scale. Errors
      made by surgeons were quantified by studying the video recording of the tasks.
      Anastomosis quality was quantified using scores for knot security, symmetry of
      suture, position of suture and apposition of anastomosis. RESULTS: The time taken
      to complete the task by the laparoscopic approach was on average 221 s, compared
      with 55 s for the open approach and 116 s for the robot-assisted approach (anova,
      P < 0.005). The number of errors and the level of self-reported discomfort were
      highest for the laparoscopic approach (anova, P < 0.005). Limitations of the
      present study include the small sample size and variation in prior surgical
      experience of the participants. CONCLUSIONS: In an in vitro model of anastomosis
      surgery, robot-assisted surgery combines the accuracy of open surgery while
      causing lesser surgeon discomfort than laparoscopy and maintaining minimal
      access.

PMID- 25756139
TI  - Editorial: Plant and Cell Physiology--past, present and future.

PMID- 25756138
TI  - Editorial: Plant and Cell Physiology's 2015 database issue.

PMID- 25756140
TI  - Professor Donald Metcalf (1929-2014).

PMID- 25756141
TI  - Guideline for referral of patients with suspected  prostate cancer by family
      physicians and other  primary care providers.
AB  - OBJECTIVE: The aim of this guideline is to assist FPs and other primary care
      providers with recognizing features that should raise their suspicion about the
      presence of prostate cancer in their patients. COMPOSITION OF THE COMMITTEE:
      Committee members were selected from among the regional primary care leads from
      the Cancer Care Ontario Provincial Primary Care and Cancer Network and from among
      the members of the Cancer Care Ontario Genitourinary Cancer Disease Site Group.
      METHODS: This guideline was developed through systematic review of the evidence
      base, synthesis of the evidence, and formal external review involving Canadian
      stakeholders to validate the relevance of recommendations. REPORT: Evidence-based
      guidelines were developed to improve the management of patients presenting with
      clinical features of prostate cancer within the Canadian context. CONCLUSION:
      These guidelines might lead to more timely and appropriate referrals and might
      also be of value for informing the development of prostate cancer diagnostic
      programs and for helping policy makers to ensure appropriate resources are in
      place.

PMID- 25756142
TI  - Polyunsaturated fatty acids and  fetal brain development.
AB  - QUESTION: I have learned that one of the manufacturers of prenatal vitamins has
      added omega-3 fatty acids and claims that they help support fetal cognitive
      health and brain function. Is this based on evidence? ANSWER: The claim that
      polyunsaturated fatty acids help improve fetal brain and eye development has been
      made for more than a decade. Unfortunately it is not supported by evidence-based
      science. Long-term studies have failed to show such effects. Implying to women
      that using these products will improve the brain development of their children is
      unwarranted and misleading. Health Canada should clarify the contradictions in
      its statements about omega-3 fatty acids.

PMID- 25756143
TI  - National Institute for Health and   Care Excellence.

PMID- 25756144
TI  - Human papillomavirus vaccination for boys.
AB  - QUESTION: In Canada, generally provincial human papillomavirus (HPV) vaccination
      programs exist for only the female population. What should I recommend when
      parents and teenage boys ask about male HPV vaccination? ANSWER: The quadrivalent
      HPV vaccine is effective and will reduce the incidence of disease in boys and
      girls. The quadrivalent HPV vaccination is approved and recommended for both boys
      and girls in Canada. Public funding for male vaccination is available in Prince
      Edward Island and Alberta. The remaining provinces and territories will need to
      consider cost-effectiveness analyses before expanding their female-only
      vaccination programs to include the male population.

PMID- 25756145
TI  - Cardiac health benefits of light drinking brought  into question.

PMID- 25756146
TI  - Systematic review of clinical features of  suspected prostate cancer in primary
      care.
AB  - OBJECTIVE: To systematically review the literature and provide an update and
      integration of existing peer-reviewed guidelines with recent systematic reviews
      and with primary studies related to the early recognition and management of
      prostate cancer in primary care. DATA SOURCES: We searched MEDLINE and EMBASE for
      relevant articles. The quality of the evidence to support existing guideline
      recommendations and the consistency of recommendations with updated evidence were
      assessed. Applicability in a Canadian primary care setting was also evaluated.
      STUDY SELECTION: All studies conducted in the primary care setting that provided
      information on clinical features predictive of prostate cancer were included.
      Also, studies that assessed the accuracy of nomograms to predict prostate cancer
      were reviewed. SYNTHESIS: The findings suggest that lower urinary tract symptoms
      are not highly predictive of prostate cancer. However, evidence suggests that FPs
      might be good at discriminating between patients with and without prostate cancer
      using digital rectal examination and prostate-specific antigen testing. Nomograms
      might also be useful in assessing patients for aggressive prostate cancers.
      CONCLUSION: The results of this review can be used to inform recommendations for
      referral for suspected prostate cancer in the primary care setting. They could
      also inform development of prostate cancer diagnostic assessment programs.

PMID- 25756147
TI  - Physicians' perspectives on cancer survivors' work integration issues.
AB  - OBJECTIVE: To explore physicians' perspectives on supporting cancer survivors'
      work integration (WI) issues. DESIGN: Using vignette methodology, 10 physicians
      were individually interviewed. Interviews were audiorecorded, transcribed, and
      subsequently analyzed. SETTING: Ontario. PARTICIPANTS: A total of 10 physicians
      participated: 5 oncologists and 5 FPs. METHODS: An inductive interpretive
      description approach was used to identify themes across the entire data set. MAIN
      FINDINGS: Physicians primarily focused on patients' medical needs and did not
      spontaneously address WI issues with them. Instead, it was their patients who
      raised WI issues, most often owing to insurance requirements. Physicians readily
      completed insurance forms to aid patients' well-being, but they did not believe
      their guidance was empirically sound based upon their limited WI training;
      rather, they recognized other health professionals, such as occupational
      therapists, as being better equipped to address cancer survivors' WI issues.
      Despite this recognition, referrals for WI support were not routinely facilitated
      owing to a lack of resources or knowledge. CONCLUSION: Owing to a lack of
      training and time, as well as the belief that WI issues are not part of their
      mandate of care, physicians perceive themselves as ill-equipped to address cancer
      survivors' WI issues. These findings underscore the need for enhanced awareness
      of cancer survivors' WI issues and the need for accessible support services
      offered by duly trained health care professionals, such as occupational
      therapists, ideally working in a multidisciplinary team to holistically address
      cancer survivors' unique needs.

PMID- 25756148
TI  - Identifying predictive morphologic  features of malignancy in eyelid lesions.
AB  - OBJECTIVE: To determine features of eyelid lesions most predictive of malignancy,
      and to design a key to assist general practitioners in the triaging of such
      lesions. DESIGN: Prospective observational study. SETTING: Department of
      Ophthalmology at Queen's University in Kingston, Ont. PARTICIPANTS: A total of
      199 consecutive periocular lesions requiring biopsy or excision were included.
      MAIN OUTCOME MEASURES: First, potential features suggestive of malignancy for
      eyelid lesions were identified based on a survey sent to Canadian oculoplastic
      surgeons. The sensitivity, specificity, and odds ratios (ORs) of these features
      were then determined using 199 consecutive photographed eyelid lesions of
      patients who presented to the Department of Ophthalmology and underwent biopsy or
      excision. A triage key was then created based on the features with the highest
      ORs, and it was pilot-tested by a group of medical students. RESULTS: Of the 199
      lesions included, 161 (80.9%) were benign and 38 (19.1%) were malignant. The 3
      features with the highest ORs in predicting malignancy were infiltration (OR =
      18.2, P < .01), ulceration (OR = 14.7, P < .01), and loss of eyelashes (OR = 6.0,
      P < .01). The acronym LUI (loss of eyelashes, ulceration, infiltration) was
      created to assist in memory recall. After watching a video describing the LUI
      triage key, the mean total score of a group of medical students for correctly
      identifying malignant lesions increased from 46% to 70% (P < .001). CONCLUSION:
      Differentiating benign from malignant eyelid lesions can be difficult even for
      experienced physicians. The LUI triage key provides physicians with an evidence
      based, easy-to-remember system for assisting in the triaging of these lesions.

PMID- 25756149
TI  - Plant life on gypsum: a review of its multiple facets.
AB  - The adaptation of plants to particular soil types has long intrigued biologists.
      Gypsum soils occupy large areas in many regions of the world and host a striking
      biological diversity, but their vegetation has been much less studied than that
      developing over serpentine or saline soils. Herein, we review all aspects of
      plant life on gypsum ecosystems, discuss the main processes driving their
      structure and functioning, and highlight the main conservation threats that they
      face. Plant communities in gypsum habitats typically show distinctive bands at
      very small spatial scales, which are mainly determined by topography. Plants
      living on gypsum soils can be classified into three categories: (i) wide
      gypsophiles are specialists that can penetrate the physical soil crust during
      early life stages and have physiological adjustments to cope with the chemical
      limitations imposed by gypsum soils; (ii) narrow gypsophiles are refugee plants
      which successfully deal with the physical soil crust and can tolerate these
      chemical limitations but do not show specific adaptations for this type of soils;
      and (iii) gypsovags are non-specialist gypsum plants that can only thrive in
      gypsum soils when the physical crust is absent or reduced. Their ability to
      survive in gypsum soils may also be mediated by below-ground interactions with
      soil microorganisms. Gypsophiles and gypsovags show efficient germination at low
      temperatures, seed and fruit heteromorphism within and among populations, and
      variation in seed dormancy among plants and populations. In gypsum ecosystems,
      spatio-temporal changes in the composition and structure of above-ground
      vegetation are closely related to those of the soil seed bank. Biological soil
      crusts (BSCs) dominated by cyanobacteria, lichens and mosses are conspicuous in
      gypsum environments worldwide, and are important drivers of ecosystem processes
      such as carbon and nitrogen cycling, water infiltration and run-off and soil
      stability. These organisms are also important determinants of the structure of
      annual plant communities living on gypsum soils. The short-distance seed
      dispersal of gypsophiles is responsible for the high number of very narrow
      endemisms typically found in gypsum outcrops, and suggests that these species are
      evolutionarily old taxa due to the time they need to colonize isolated gypsum
      outcrops by chance. Climate change and habitat fragmentation negatively affect
      both plants and BSCs in gypsum habitats, and are among the major threats to these
      ecosystems. Gypsum habitats and specialists offer the chance to advance our
      knowledge on restrictive soils, and are ideal models not only to test important
      evolutionary questions such as tolerance to low Ca/Mg proportions in soils, but
      also to improve the theoretical framework of community ecology and ecosystem
      functioning.

PMID- 25756150
TI  - Similar success rates for single and multiple debridement surgery for acute hip
      arthroplasty infection--reply.

PMID- 25756151
TI  - Reply: To PMID 24957400.

PMID- 25756152
TI  - Economic burden of pre-diabetes up 74% over 5 years.

PMID- 25756153
TI  - Clinical features associated with copy number variations of the 14q32 imprinted
      gene cluster.
AB  - Uniparental disomy (UPD) for imprinted chromosomes can cause abnormal phenotypes
      due to absent or overexpression of imprinted genes. UPD(14)pat causes a unique
      constellation of features including thoracic skeletal anomalies, polyhydramnios,
      placentomegaly, and limited survival; its hypothesized cause is overexpression of
      paternally expressed RTL1, due to absent regulatory effects of maternally
      expressed RTL1as. UPD(14)mat causes a milder condition with hypotonia, growth
      failure, and precocious puberty; its hypothesized cause is absence of paternally
      expressed DLK1. To more clearly establish how gains and losses of imprinted genes
      can cause disease, we report six individuals with copy number variations of the
      imprinted 14q32 region identified through clinical microarray-based comparative
      genomic hybridization. Three individuals presented with UPD(14)mat-like
      phenotypes (Temple syndrome) and had apparently de novo deletions spanning the
      imprinted region, including DLK1. One of these deletions was shown to be on the
      paternal chromosome. Two individuals with UPD(14)pat-like phenotypes had 122
      154kb deletions on their maternal chromosomes that included RTL1as but not the
      differentially methylated regions that regulate imprinted gene expression,
      providing further support for RTL1 overexpression as a cause for the UPD(14)pat
      phenotype. The sixth individual is tetrasomic for a 1.7Mb segment, including the
      imprinted region, and presents with intellectual disability and seizures but
      lacks significant phenotypic overlap with either UPD(14) syndrome. Therefore, the
      14q32 imprinted region is dosage sensitive, with deletions of different critical
      regions causing UPD(14)mat- and UPD(14)pat-like phenotypes, while copy gains are
      likely insufficient to recapitulate these phenotypes.

PMID- 25756154
TI  - Co-segregation of Freiberg's infraction with a familial translocation
      t(5;7)(p13.3;p22.2) ascertained by a child with cri du chat syndrome and
      brachydactyly type A1B.
AB  - The identification of chromosomal breakpoints in association with human abnormal
      phenotypes can enable elucidation of gene function. We report on epiphyseal
      aseptic necrosis of the lesser head of the second metatarsal bone, known as
      Freiberg's infraction (FI), in two female carriers of the apparently balanced
      t(5;7)(p13.3;p22.2) ascertained by a 16-year-old girl with cri-du-chat syndrome
      and unusual skeletal features in association with an unbalanced translocation
      der(5) t(5;7)(p13.3;p22.2). Mapping of the chromosome breakpoints using
      fluorescent in situ hybridization (FISH) narrowed them to the coding sequence of
      ADAMTS12 on chromosome 5p13.3 and SDK1 on 7p22.2. In addition, several skeletal
      abnormalities classified as brachydactyly type A1B (BDA1B) were present in the
      proband and in both carriers of t(5;7)(p13.3;p22.2), suggesting a potential role
      of ADAMTS12 in the development of the BDA1B observed in this family.

PMID- 25756155
TI  - Adult-onset langerhans cell  histiocytosis mimicking  folliculitis decalvans.

PMID- 25756156
TI  - Reply.

PMID- 25756157
TI  - Verrucous carcinoma developing  in a long standing case of  ulcerative lichen
      planus of sole: a  rare case report.

PMID- 25756158
TI  - 2015 Is the time for Global action.

PMID- 25756159
TI  - Ebola the United Nations are looking for  volunteers midwives.

PMID- 25756161
TI  - Actions to end obstetric fistula.

PMID- 25756160
TI  - Call to action on improving water  sanitation and hygiene for maternal and 
      newborn health.

PMID- 25756163
TI  - Research priorities to improve the care of women with female genital mutilation.

PMID- 25756162
TI  - Elevated alanine aminotransferase (ALT) in the deceased donor: impact on early
      post-transplant liver allograft function.
AB  - BACKGROUND & AIMS: Serum alanine aminotransferase (ALT) levels are frequently
      elevated with liver injury and such elevations are common in deceased organ
      donors. The impact of this injury on early liver allograft function has not been
      well described. This study analyses the immediate function and 1-year graft and
      patient survival for liver allografts stratified by peak serum ALT levels in the
      deceased donor. METHODS: The on-site organ procurement records for 1348
      consecutive deceased liver donors were reviewed (2001-2011). Serum ALT was
      categorized into three study groups: normal/mild elevation, 0-499 MU/L; moderate
      elevation, 500-999 MU/L (>10* upper limit of normal) and severe elevation, >=1000
      MU/L (>20* upper limit of normal). Outcomes included early graft function and
      graft loss, and 1-year graft and patient survival. RESULTS: Distribution of
      subjects included: normal/mild, 1259 (93%); moderate, 34 (3%) and severe, 55
      (4%). Risk of 30-day graft loss for the three study groups was: 72 (6%), 3 (9%)
      and 3 (6%) (P = 0.74). Graft and patient survival at 1 year for the three groups
      was: normal/mild, 1031 (87%), 1048 (88%); moderate, 31 (91%), 31 (91%) and
      severe, 43 (88%), 44 (90%) (P = 0.71, 0.79). Cox proportional hazards modelling
      of survival while controlling for donor age and recipient model for end-stage
      liver disease score (MELD) demonstrates no statistically significant difference
      among the three study groups. CONCLUSIONS: This study demonstrates clinical
      equivalence in early graft function and 1-year graft and patient survival for
      donor livers with varying peak levels of serum ALT. These donor allografts may,
      therefore, be utilized successfully.

PMID- 25756164
TI  - World prematurity day.

PMID- 25756165
TI  - Saving lives, improving mother's care report.

PMID- 25756166
TI  - Prioritising sexual and reproductive  health will save millions of lives,says 
      new report.

PMID- 25756167
TI  - Boys are more likely to be stillborn than  girls.

PMID- 25756168
TI  - Effects of bovine lactoferrin to oral Candida albicans and Candida  glabrata
      isolates recovered from the saliva in elderly people.
AB  - The effects of bovine lactoferrin (bLF) on the growth of Candida species and on
      inflammatory cytokine production in gingival keratinocytes, NDUSD-1 co-cultured
      with Candida strains were investigated. The results showed that bLF at 10 and 100
      lg/mL significantly inhibits the growth of two C. albicans strains and two C.
      glabrata strains isolated from the saliva of elderly people requiring nursing
      care, respectively. The levels of inflammatory cytokines, interleukin (IL)-6, and
      IL-8 in NDUSD-1 cocultured with each of these four Candida strains were measured.
      C. albicans tend to have a more potent capacity than C. glabrata to induce the
      production of the inflammatory cytokines in NDUSD-1. The levels of IL-6 and IL-8
      in NDUSD-1 co-cultured with each of Candida species were measured after addition
      of bLF. bLF at concentrations from 1 to 100 lg/mL significantly inhibited the
      production of these cytokines in NDUSD-1 co-cultured with Candida species. These
      findings suggest that bLF may be useful in reducing the risk of aspiration
      pneumonia among elderly people requiring care for whom oral care is difficult.

PMID- 25756169
TI  - [Eye clinics and practices -- communicating pipelines].

PMID- 25756170
TI  - [Be careful with the use of images and texts: ask the Author!].

PMID- 25756171
TI  - [Farewell to the practice -- management of the successful sale].

PMID- 25756172
TI  - Cardiology fellows' dilemma of academic versus private practice: is it the wrong
      question?

PMID- 25756173
TI  - High sucrose intake at 3 years of age is associated with increased salivary
      counts of mutans streptococci and lactobacilli, and with increased caries rate
      from 3 to 16 years of age.
AB  - OBJECTIVE: We aimed to study the long-term associations between sucrose intake
      (SI), selected representatives of the cariogenic oral flora, and the dental
      health of children from 3 to 16 years of age. METHODS: At 7 months of age 1,062
      infants (540 intervention; 522 controls) were included in the prospective,
      randomised STRIP-project aimed at restricting the child's saturated fat and
      cholesterol intake to prevent atherosclerosis when they become adults. At 3 years
      of age, every fifth child was invited (n = 178) to an oral sub-study, and 148 (78
      boys) children attended. A restudy was conducted on 135 children aged 6, 127 aged
      9, 114 aged 12 and 88 aged 16. SI using 4-day food records, plate-cultured mutans
      streptococci (MS), salivary lactobacilli (LB) and yeasts using commercial kits
      (Orion Diagnostica, Espoo Finland), toothbrushing frequency using fluoridated
      toothpaste and dental health expressed as d 3 mft/D 3 MFT were regularly
      recorded. RESULTS: The SI of children whose intake was >= 10 E% (high SI) at 3
      years remained high throughout the entire follow-up (p < 0.001, GLM for repeated
      measures) period, and they had higher salivary MS and LB counts (p = 0.024 and p
      = 0.068, respectively, GLM) than their counterparts whose SI was below 10 E% (low
      SI). No differences in toothbrushing habits were found between the high and low
      SI-groups. Caries-survival was strongly associated with low 6-year-counts of MS
      (p = 0.008, Cox regression analysis), and the d 3 mft/D 3 MFTscores of the high
      SI-group were higher than those of the low SI-group (p = 0.046, GLM).
      CONCLUSIONS: High SI at 3 years was associated with high MS-counts ( >= 10 5
      cfu/ml) and with a high risk for caries.

PMID- 25756174
TI  - The United States has struggled with how to adequately provide health  care for
      its poor and middle class for a long time.

PMID- 25756175
TI  - Simultaneous use of endoscopic resection and radiofrequency ablation is not  safe
      in an esophageal porcine model.
AB  - Radiofrequency ablation (RFA) is safe and effective for eradication of Barrett's
      esophagus after endoscopic resection (ER) of neoplasia. Widespread ER, however,
      is likely to induce stenosis, hampering subsequent circumferential RFA. A 'single
      step' procedure with ER and circumferential RFA in the same session may avoid
      this problem. Two variants are possible: circumferential RFA of Barrett's
      esophagus including the lesion followed by ER of the ablated lesion ('RFA->ER'),
      or ER of the lesion directly followed by circumferential RFA of remaining
      Barrett's esophagus including the resection wound ('ER->RFA'). First aim was to
      evaluate perforation risk of 'ER->RFA' using increasing RFA energies. Second aim
      was to compare stenosis rate after 'ER->RFA' versus 'RFA->ER'. In Experiment 1,
      24 areas in six pigs underwent widespread ER directly followed by circumferential
      RFA with increasing energies (2 x 10, 2 x 12-6 x 12 J/cm(2)) in the esophagus. In
      Experiment 2, eight pigs each had four treatment areas randomized: 'ER->RFA', RFA
      alone, ER alone, and 'RFA->ER'. No acute perforations occurred when ablating ER
      wounds. Two delayed perforations occurred: one in experiment 1, another in
      experiment n2 at the 'ER->RFA' area. The remaining seven pigs in experiment 2
      showed stenosis in all 'ER->RFA' and 'RFA->ER' areas versus 5/7 RFA alone areas,
      and 0/7 ER alone areas. In conclusion, the 'single step' variant 'ER->RFA' is not
      safe in this porcine model and seems therefore not ethical to evaluate in humans
      at this stage. Given the high rate of stenosis after 'RFA->ER' and RFA alone, one
      might question the validity of the porcine model for this type of experiments.

PMID- 25756176
TI  - Letter to the editor regarding "simultaneous determination of residues in pollen
      and high-fructose corn syrup from eight neonicotinoid insecticides by liquid
      chromatography-tandem mass spectrometry".

PMID- 25756177
TI  - A genomic screen revealing the importance of vesicular trafficking pathways in
      genome maintenance and protection against genotoxic stress in diploid
      Saccharomyces cerevisiae cells.
AB  - The ability to survive stressful conditions is important for every living cell.
      Certain stresses not only affect the current well-being of cells but may also
      have far-reaching consequences. Uncurbed oxidative stress can cause DNA damage
      and decrease cell survival and/or increase mutation rates, and certain substances
      that generate oxidative damage in the cell mainly act on DNA. Radiomimetic zeocin
      causes oxidative damage in DNA, predominantly by inducing single- or double
      strand breaks. Such lesions can lead to chromosomal rearrangements, especially in
      diploid cells, in which the two sets of chromosomes facilitate excessive and
      deleterious recombination. In a global screen for zeocin-oversensitive mutants,
      we selected 133 genes whose deletion reduces the survival of zeocin-treated
      diploid Saccharomyces cerevisiae cells. The screen revealed numerous genes
      associated with stress responses, DNA repair genes, cell cycle progression genes,
      and chromatin remodeling genes. Notably, the screen also demonstrated the
      involvement of the vesicular trafficking system in cellular protection against
      DNA damage. The analyses indicated the importance of vesicular system integrity
      in various pathways of cellular protection from zeocin-dependent damage,
      including detoxification and a direct or transitional role in genome maintenance
      processes that remains unclear. The data showed that deleting genes involved in
      vesicular trafficking may lead to Rad52 focus accumulation and changes in total
      DNA content or even cell ploidy alterations, and such deletions may preclude
      proper DNA repair after zeocin treatment. We postulate that functional vesicular
      transport is crucial for sustaining an integral genome. We believe that the
      identification of numerous new genes implicated in genome restoration after
      genotoxic oxidative stress combined with the detected link between vesicular
      trafficking and genome integrity will reveal novel molecular processes involved
      in genome stability in diploid cells. 

PMID- 25756178
TI  - Evaluation of the synuclein-gamma (SNCG) gene as a PPARgamma target in murine
      adipocytes, dorsal root ganglia somatosensory neurons, and human adipose tissue.
AB  - Recent evidence in adipocytes points to a role for synuclein-gamma in metabolism
      and lipid droplet dynamics, but interestingly this factor is also robustly
      expressed in peripheral neurons. Specific regulation of the synuclein-gamma gene
      (Sncg) by PPARgamma requires further evaluation, especially in peripheral
      neurons, prompting us to test if Sncg is a bona fide PPARgamma target in murine
      adipocytes and peripheral somatosensory neurons derived from the dorsal root
      ganglia (DRG). Sncg mRNA was decreased in 3T3-L1 adipocytes (~68%) by
      rosiglitazone, and this effect was diminished by the PPARgamma antagonist
      T0070907. Chromatin immunoprecipitation experiments confirmed PPARgamma protein
      binding at two promoter sequences of Sncg during 3T3-L1 adipogenesis.
      Rosiglitazone did not affect Sncg mRNA expression in murine cultured DRG neurons.
      In subcutaneous human WAT samples from two cohorts treated with pioglitazone (>11
      wks), SNCG mRNA expression was reduced, albeit highly variable and most evident
      in type 2 diabetes. Leptin (Lep) expression, thought to be coordinately-regulated
      with Sncg based on correlations in human adipose tissue, was also reduced in 3T3
      L1 adipocytes by rosiglitazone. However, Lep was unaffected by PPARgamma
      antagonist, and the LXR agonist T0901317 significantly reduced Lep expression
      (~64%) while not impacting Sncg. The results support the concept that synuclein
      gamma shares some, but not all, gene regulators with leptin and is a PPARgamma
      target in adipocytes but not DRG neurons. Regulation of synuclein-gamma by cues
      such as PPARgamma agonism in adipocytes is logical based on recent evidence for
      an important role for synuclein-gamma in the maintenance and dynamics of
      adipocyte lipid droplets. 

PMID- 25756179
TI  - Sugar industry influence on the scientific agenda of the National Institute of
      Dental Research's 1971 National Caries Program: a historical analysis of internal
      documents.
AB  - BACKGROUND: In 1966, the National Institute of Dental Research (NIDR) began
      planning a targeted research program to identify interventions for widespread
      application to eradicate dental caries (tooth decay) within a decade. In 1971,
      the NIDR launched the National Caries Program (NCP). The objective of this paper
      is to explore the sugar industry's interaction with the NIDR to alter the
      research priorities of the NIDR NCP. METHODS AND FINDINGS: We used internal cane
      and beet sugar industry documents from 1959 to 1971 to analyze industry actions
      related to setting research priorities for the NCP. The sugar industry could not
      deny the role of sucrose in dental caries given the scientific evidence. They
      therefore adopted a strategy to deflect attention to public health interventions
      that would reduce the harms of sugar consumption rather than restricting intake.
      Industry tactics included the following: funding research in collaboration with
      allied food industries on enzymes to break up dental plaque and a vaccine against
      tooth decay with questionable potential for widespread application, cultivation
      of relationships with the NIDR leadership, consulting of members on an NIDR
      expert panel, and submission of a report to the NIDR that became the foundation
      of the first request for proposals issued for the NCP. Seventy-eight percent of
      the sugar industry submission was incorporated into the NIDR's call for research
      applications. Research that could have been harmful to sugar industry interests
      was omitted from priorities identified at the launch of the NCP. Limitations are
      that this analysis relies on one source of sugar industry documents and that we
      could not interview key actors. CONCLUSIONS: The NCP was a missed opportunity to
      develop a scientific understanding of how to restrict sugar consumption to
      prevent tooth decay. A key factor was the alignment of research agendas between
      the NIDR and the sugar industry. This historical example illustrates how industry
      protects itself from potentially damaging research, which can inform policy
      makers today. Industry opposition to current policy proposals-including a World
      Health Organization guideline on sugars proposed in 2014 and changes to the
      nutrition facts panel on packaged food in the US proposed in 2014 by the US Food
      and Drug Administration-should be carefully scrutinized to ensure that industry
      interests do not supersede public health goals.

PMID- 25756180
TI  - A genome scan for selection signatures in pigs.
AB  - Identifying signatures of selection can provide a straightforward insight into
      the mechanism of artificial selection and further uncover the causal genes
      related to the phenotypic variation. Based on Illumina Porcine60KSNP chip data,
      four complementary methods, Long-Range Haplotype (LRH), Tajima's D, Cross
      Population Extend Haplotype Homozygosity Test (XPEHH) and FST, were implemented
      in this study to detect the selection signatures in the whole genome of one
      typical Chinese indigenous breed, Rongchang, one Chinese cultivated breed,
      Songliao, and two western breeds, Landrace and Yorkshire. False Discovery Rate
      (FDR) was implemented to control the false positive rates. In our study, a total
      of 159, 127, 179 and 159 candidate selection regions with average length of 0.80
      Mb, 0.73 Mb, 0.78 Mb and 0.73 Mb were identified in Landrace, Rongchang, Songliao
      and Yorkshire, respectively, that span approximately 128.00 Mb, 92.38 Mb, 130.30
      Mb and 115.40 Mb and account for approximately 3.74-5.33% of genome across all
      autosomes. The selection regions of 11.52 Mb shared by Landrace and Yorkshire
      were the longest when chosen pairs from the pool of the four breeds were
      examined. The overlaps between Yorkshire and Songliao, approximately 9.20 Mb,
      were greater than those of Yorkshire and Rongchang. Meanwhile, the overlaps
      between Landrace and Songliao were greater than those of Landrace and Rongchang
      but less than those of Songliao and Ronchang. Bioinformatics analysis showed that
      the genes/QTLs relevant to fertility, coat color, and ear morphology were found
      in candidate selection regions. Some genes, such as LEMD3, MC1R, KIT, TRHR etc.
      that were reported under selection, were confirmed in our study, and this
      analysis also demonstrated the diversity of breeds. 

PMID- 25756181
TI  - Leptin signaling is required for adaptive changes in food intake, but not energy
      expenditure, in response to different thermal conditions.
AB  - Survival of free-living animals depends on the ability to maintain core body
      temperature in the face of rapid and dramatic changes in their thermal
      environment. If food intake is not adjusted to meet the changing energy demands
      associated with changes of ambient temperature, a serious challenge to body
      energy stores can occur. To more fully understand the coupling of
      thermoregulation to energy homeostasis in normal animals and to investigate the
      role of the adipose hormone leptin to this process, comprehensive measures of
      energy homeostasis and core temperature were obtained in leptin-deficient ob/ob
      mice and their wild-type (WT) littermate controls when housed under cool (14
      degrees C), usual (22 degrees C) or ~ thermoneutral (30 degrees C) conditions.
      Our findings extend previous evidence that WT mice robustly defend normothermia
      in response to either a lowering (14 degrees C) or an increase (30 degrees C) of
      ambient temperature without changes in body weight or body composition. In
      contrast, leptin-deficient, ob/ob mice fail to defend normothermia at ambient
      temperatures lower than thermoneutrality and exhibit marked losses of both body
      fat and lean mass when exposed to cooler environments (14 degrees C). Our
      findings further demonstrate a strong inverse relationship between ambient
      temperature and energy expenditure in WT mice, a relationship that is preserved
      in ob/ob mice. However, thermal conductance analysis indicates defective heat
      retention in ob/ob mice, irrespective of temperature. While a negative
      relationship between ambient temperature and energy intake also exists in WT
      mice, this relationship is disrupted in ob/ob mice. Thus, to meet the
      thermoregulatory demands of different ambient temperatures, leptin signaling is
      required for adaptive changes in both energy intake and thermal conductance. A
      better understanding of the mechanisms coupling thermoregulation to energy
      homeostasis may lead to the development of new approaches for the treatment of
      obesity. 

PMID- 25756182
TI  - Soluble interleukin-15 complexes are generated in vivo by type I interferon
      dependent and independent pathways.
AB  - Interleukin (IL)-15 associates with IL-15Ralpha on the cell surface where it can
      be cleaved into soluble cytokine/receptor complexes that have the potential to
      stimulate CD8 T cells and NK cells. Unfortunately, little is known about the in
      vivo production of soluble IL-15Ralpha/IL-15 complexes (sIL-15 complexes),
      particularly regarding the circumstances that induce them and the mechanisms
      responsible. The main objective of this study was to elucidate the signals
      leading to the generation of sIL-15 complexes. In this study, we show that sIL-15
      complexes are increased in the serum of mice in response to Interferon (IFN)
      alpha. In bone marrow derived dendritic cells (BMDC), IFN-alpha increased the
      activity of ADAM17, a metalloproteinase implicated in cleaving IL-15 complexes
      from the cell surface. Moreover, knocking out ADAM17 in BMDCs prevented the
      ability of IFN-alpha to induce sIL-15 complexes demonstrating ADAM17 as a
      critical protease mediating cleavage of IL-15 complexes in response to type I
      IFNs. Type I IFN signaling was required for generating sIL-15 complexes as in
      vivo induction of sIL-15 complexes by Poly I:C stimulation or total body
      irradiation (TBI) was impaired in IFNAR-/- mice. Interestingly, serum sIL-15
      complexes were also induced in mice infected with Vesicular stomatitis virus
      (VSV) or mice treated with agonistic CD40 antibodies; however, sIL-15 complexes
      were still induced in IFNAR-/- mice after VSV infection or CD40 stimulation
      indicating pathways other than type I IFNs induce sIL-15 complexes. Overall, this
      study has shown that type I IFNs, VSV infection, and CD40 stimulation induce sIL
      15 complexes suggesting the generation of sIL-15 complexes is a common event
      associated with immune activation. These findings reveal an unrealized mechanism
      for enhanced immune responses occurring during infection, vaccination,
      inflammation, and autoimmunity. 

PMID- 25756183
TI  - Factors associated with untreated diabetes: analysis of data from 20,496
      participants in the Japanese National Health and Nutrition Survey.
AB  - OBJECTIVE: We aimed to examine factors associated with untreated diabetes in a
      nationally representative sample of the Japanese population. RESEARCH DESIGN AND
      METHODS: We pooled data from the Japanese National Health and Nutrition Survey
      from 2005 to 2009 (n = 20,496). Individuals aged 20 years and older were included
      in the analysis. We classified participants as having diabetes if they had HbA1c
      levels >=6.5% (>=48 mmol/mol). People with diabetes who self-reported that they
      were not currently receiving diabetic treatment were considered to be untreated.
      We conducted a multinomial logistic regression analysis to determine factors
      associated with untreated diabetes relative to non-diabetic individuals. RESULTS:
      Of 20,496 participants who were included in the analysis, untreated diabetes was
      present in 748 (3.6%). Among participants with untreated diabetes, 48.3% were
      previously diagnosed with diabetes, and 46.5% had HbA1c levels >=7.0% (>=53
      mmol/mol). Participants with untreated diabetes were significantly more likely
      than non-diabetic participants to be male, older, and currently smoking, have
      lower HDL cholesterol levels and higher BMI, non-HDL cholesterol levels, and
      systolic blood pressure. CONCLUSIONS: A substantial proportion of people in Japan
      with untreated diabetes have poor glycemic control. Targeting relevant factors
      for untreated diabetes in screening programs may be effective to enhance the
      treatment and control of diabetes.

PMID- 25756184
TI  - How could hospitalisations at the end of life have been avoided? A qualitative
      retrospective study of the perspectives of general practitioners, nurses and
      family carers.
AB  - BACKGROUND: Although many patients prefer to stay and die at home at the end of
      life, many are hospitalised. Little is known about how to avoid hospitalisations
      for patients living at home. AIM: To describe how hospitalisation at the end of
      life can be avoided, from the perspective of the GPs, nurses and family carers.
      METHOD: A qualitative design with face-to-face interviews was used. Taking 30
      cases of patients who died non-suddenly, 26 GPs, 15 nurses and 18 family carers
      were interviewed in depth. Of the 30 patients, 20 were hospitalised and 10 were
      not hospitalised in the last three months of life. RESULTS: Five key themes that
      could help avoid hospitalisation at the end of life emerged from the interviews.
      The key themes were: 1) marking the approach of death, and shifting the mindset;
      2) being able to provide acute treatment and care at home; 3) anticipatory
      discussions and interventions to deal with expected severe problems; 4) guiding
      and monitoring the patient and family in a holistic way through the illness
      trajectory; 5) continuity of treatment and care at home. If these five key themes
      are adopted in an interrelated way, this could help avoid hospitalisations,
      according to GPs, nurses and family carers. CONCLUSIONS: The five key themes
      described in this study can be seen as strategies that could help in avoiding
      hospitalisation at the end of life. It is recommended that for all patients
      residing at home, GPs and community nurses work together as a team from the
      moment that it is marked that death is approaching up to the end of life.

PMID- 25756185
TI  - DivStat: a user-friendly tool for single nucleotide polymorphism analysis of
      genomic diversity.
AB  - Recent developments have led to an enormous increase of publicly available large
      genomic data, including complete genomes. The 1000 Genomes Project was a major
      contributor, releasing the results of sequencing a large number of individual
      genomes, and allowing for a myriad of large scale studies on human genetic
      variation. However, the tools currently available are insufficient when the goal
      concerns some analyses of data sets encompassing more than hundreds of base pairs
      and when considering haplotype sequences of single nucleotide polymorphisms
      (SNPs). Here, we present a new and potent tool to deal with large data sets
      allowing the computation of a variety of summary statistics of population genetic
      data, increasing the speed of data analysis. 

PMID- 25756186
TI  - Rates of karyotypic evolution in Estrildid finches differ between island and
      continental clades.
AB  - Reasons why chromosomal rearrangements spread to fixation and frequently
      distinguish related taxa remain poorly understood. We used cytological
      descriptions of karyotype to identify large pericentric inversions between
      species of Estrildid finches (family Estrildidae) and a time-dated phylogeny to
      assess the genomic, geographic, and phylogenetic context of karyotype evolution
      in this group. Inversions between finch species fixed at an average rate of one
      every 2.26 My. Inversions were twice as likely to fix on the sex chromosomes
      compared to the autosomes. A high repeat density on the sex chromosomes may
      increase mutation rates, but other explanations via mutagenic input are not
      supported, as the number of inversions on a chromosome does not correlate with
      its length or map size. Inversions have fixed 3.3* faster in three continental
      clades than in two island chain clades, and fixation rate correlates with both
      range size and the number of sympatric species pairs. These results point to
      adaptation as the dominant mechanism driving fixation and suggest a role for gene
      flow in karyotype divergence. A review shows that the rapid karyotype evolution
      observed in the Estrildid finches appears to be more general across birds, and by
      implication other understudied taxa.

PMID- 25756187
TI  - Estimation of the rate of tooth wear in permanent incisors: a cross-sectional
      digital radiographic study.
AB  - This study used conventional digital radiography to estimate the rate of tooth
      wear (TW) of maxillary and mandibular central incisors based on a cross-sectional
      study design. The crown length of 1239 permanent maxillary and mandibular central
      incisors from 346 persons (age groups: 10, 25, 40, 55 and 70 years +/- 3) were
      measured by three calibrated dentists. Study teeth were intact incisally, had
      clearly visible incisal edges and cementoenamel junctions and had natural tooth
      antagonists. Measures were based on digital radiographic images (N = 666)
      archived in MiPACS within the electronic health record (axiUm((r))) from the
      College of Dentistry patient database. Incisor crown length decreased at a linear
      rate in both arches over the 60 years represented by the age groups. The average
      crown length for maxillary incisors in the youngest age group was 11.94 mm, which
      decreased by an average of 1.01 mm by median age 70. For mandibular incisors, the
      average crown length in the youngest age group was 9.58 mm, which decreased by an
      average of 1.46 mm in the oldest age group. Males and females showed similar
      rates of TW. Regardless of age, females demonstrated smaller mean crown height
      for maxillary incisors than males (P < 0.0001). Measures by the examiners
      demonstrated good agreement, with an interclass correlation coefficient of 0.869
      and an average intra-examiner correlation of 99.5%, based on repeated
      measurements (n = 100). TW was estimated to average 1.01 mm for maxillary central
      incisors and 1.46 mm for mandibular central incisors by age 70 years.

PMID- 25756188
TI  - Adaptive mutations alter antibody structure and dynamics during affinity
      maturation.
AB  - While adaptive mutations can bestow new functions on proteins via the
      introduction or optimization of reactive centers, or other structural changes, a
      role for the optimization of protein dynamics also seems likely but has been more
      difficult to evaluate. Antibody (Ab) affinity maturation is an example of
      adaptive evolution wherein the adaptive mutations may be identified and Abs may
      be raised to specific targets that facilitate the characterization of protein
      dynamics. Here, we report the characterization of three affinity matured Abs that
      evolved from a common germline precursor to bind the chromophoric antigen (Ag), 8
      methoxypyrene-1,3,6-trisulfonate (MPTS). In addition to characterizing the
      sequence, molecular recognition, and structure of each Ab, we characterized the
      dynamics of each complex by determining their mechanical response to an applied
      force via three-pulse photon echo peak shift (3PEPS) spectroscopy and
      deconvoluting the response into elastic, anelastic, and plastic components. We
      find that for one Ab, affinity maturation was accomplished via the introduction
      of a single functional group that mediates a direct contact with MPTS and results
      in a complex with little anelasticity or plasticity. In the other two cases, more
      mutations were introduced but none directly contact MPTS, and while their effects
      on structure are subtle, their effects on anelasticity and plasticity are
      significant, with the level of plasticity correlated with specificity, suggesting
      that the optimization of protein dynamics may have contributed to affinity
      maturation. A similar optimization of structure and dynamics may contribute to
      the evolution of other proteins. 

PMID- 25756189
TI  - Ultrasonic emissions during ice nucleation and propagation in plant xylem.
AB  - Ultrasonic acoustic emission analysis enables nondestructive monitoring of damage
      in dehydrating or freezing plant xylem. We studied acoustic emissions (AE) in
      freezing stems during ice nucleation and propagation, by combining acoustic and
      infrared thermography techniques and controlling the ice nucleation point.
      Ultrasonic activity in freezing samples of Picea abies showed two distinct
      phases: the first on ice nucleation and propagation (up to 50 AE s(-1) ;
      reversely proportional to the distance to ice nucleation point), and the second
      (up to 2.5 AE s(-1) ) after dissipation of the exothermal heat. Identical
      patterns were observed in other conifer and angiosperm species. The complex AE
      patterns are explained by the low water potential of ice at the ice-liquid
      interface, which induced numerous and strong signals. Ice propagation velocities
      were estimated via AE (during the first phase) and infrared thermography.
      Acoustic activity ceased before the second phase probably because the exothermal
      heating and the volume expansion of ice caused decreasing tensions. Results
      indicate cavitation events at the ice front leading to AE. Ultrasonic emission
      analysis enabled new insights into the complex process of xylem freezing and
      might be used to monitor ice propagation in natura.

PMID- 25756190
TI  - New onset idiosyncratic liver enzyme elevations with biological therapy in
      inflammatory bowel disease.
AB  - BACKGROUND: Anti-tumour necrosis factor alpha (anti-TNF) agents have been
      implicated in drug-induced liver injury. There is minimal data on this occurrence
      in inflammatory bowel disease (IBD) patients. AIM: To identify the
      characteristics of liver enzyme elevations following anti-TNF therapy initiation
      in IBD. METHODS: A retrospective cohort of patients initiating anti-TNF therapy
      were analysed for new onset alanine transaminase (ALT) elevation (>=60 U/L). We
      collected data on natural history, outcomes and patient characteristics compared
      with controls with persistent normal liver enzymes. Likelihood of causal
      association was assessed using the RUCAM score. RESULTS: From 1753 patients
      initiating an anti-TNF (1170 infliximab, 575 adalimumab, 8 certolizumab), 102
      (6%) developed new onset ALT elevation. In 54 (53%), this could be linked to an
      alternate aetiology. Among those with idiopathic ALT elevations, the median time
      to ALT elevation from anti-TNF initiation was 18 weeks and median peak ALT was 96
      U/L. Six underwent liver biopsy, all demonstrating hepatitis with autoimmune
      features. Compared to controls, cases were on a lower dose of infliximab (5.7 vs.
      6.7 mg/kg, P = 0.02) but were otherwise similar in body mass index, sex and age.
      On follow-up, 34 continued the anti-TNF, 14 stopped therapy and 4 initiated
      steroids. Most (85%) normalised their LFTs after a median of 17 weeks including
      28 (82%) of those who continued anti-TNF therapy. Ten patients were transitioned
      to a second anti-TNF without recurrence. CONCLUSIONS: ALT elevations occurred in
      6% of IBD patients initiating anti-TNF therapy. Most idiopathic elevations were
      mild, transient and resolved despite therapy continuation.

PMID- 25756192
TI  - BMX: a tool for computing bacterial phyletic composition from orthologous maps.
AB  - BACKGROUND: New sequencing technologies have made it possible to explore genetic
      diversity at higher resolution in microbial populations. However, our
      understanding evolutionary relationships, and comparison of closely and distantly
      related bacterial genomes from these massive datasets remains a formidable
      challenge. Numerous clustering algorithms that group genomic data based on
      homology have been developed, but new tools are still required to analyse the
      resultant orthologous maps to understand functional genetic similarities and
      their phyletic patterns (patterns of presence of absence of genes). FINDINGS:
      Bacterial Makeup eXplorer (BMX) implements an algorithm that swiftly and
      efficiently facilitates the determination of the number of orthologs in
      prokaryotic genomes employing a reference free approach, which may be further
      exploited to transfer of gene annotations. BMX is able to integrate orthologous
      maps of highly diverse prokaryotic genomes therefore making it possible to
      perform robust and scalable, multi-platform, high quality annotation transfer and
      gene-by-gene composition assessment method. In addition results are presented in
      the form of publication quality figures. CONCLUSIONS: BMX allows extensive data
      analysis of orthologous map databases to understand underlying biological
      relationships. Furthermore, BMX is portable across different platforms and can be
      installed easily. In summary, BMX allows higher resolution analysis of genomes
      from diverse bacterial populations.

PMID- 25756191
TI  - Interferon Lambda Upregulates IDO1 Expression in Respiratory Epithelial Cells
      After Influenza Virus Infection.
AB  - Influenza infection causes an increase in indoleamine 2, 3-dioxygenase (IDO)
      activity in the lung parenchyma. IDO catabolizes tryptophan into kynurenine,
      leading to immune dampening. Multiple cell types express IDO, and while IFN-gamma
      upregulates IDO in dendritic cells and macrophages, it is unclear how IDO is
      affected in respiratory epithelial cells during influenza infection. In this
      study, the role of IFN-lambda in IDO regulation was investigated after influenza
      infection of respiratory epithelial cells. IDO1 expression increased concurrently
      with IFN-lambda expression. In differentiated NHBE cells, the IDO metabolite was
      released basolaterally. Recombinant IFN-lambda upregulated IDO1 activity, and
      silencing of IFN-lambda decreased IDO1 expression during influenza infection.
      During IFN-lambda stimulation, most differentiated cell types are able to express
      IDO but during influenza infection, IDO is primarily expressed in uninfected
      cells. These studies show a role for IDO in the host response to influenza
      infection, and they provide insights into novel approaches for enhancing vaccine
      responses and therapeutic approaches. 

PMID- 25756193
TI  - Use of negative pressure wound therapy with instillation in the management of
      cervical necrotizing fasciitis.
AB  - BACKGROUND: Cervical necrotizing fasciitis is an aggressive infection that can be
      rapidly fatal if aggressive therapies are not initiated early. Negative pressure
      wound therapy has been established as an effective tool in promoting wound
      healing, but its use in the acutely infected wound has been avoided because it
      limits frequent irrigations and standard dressing changes. METHODS: We discuss a
      novel application of negative pressure wound therapy with instillation in an
      immunocompromised patient with extensive cervical necrotizing fasciitis. RESULTS:
      The negative pressure wound therapy with instillation provided pain relief by
      minimizing the frequency of dressing changes, increased the speed of healing,
      helped to control infection, and facilitated the development of a healthy wound
      bed sufficient for reconstruction with a split thickness skin graft. CONCLUSION:
      The role of negative pressure wound therapy with instillation continues to expand
      and can be used in the management of both acute and chronic wounds in the head
      and neck.

PMID- 25756194
TI  - Electrocatalytic carbon dioxide reduction by using cationic
      pentamethylcyclopentadienyl-iridium complexes with unsymmetrically substituted
      bipyridine ligands.
AB  - Eight [Ir(bpy)Cp*Cl](+) -type complexes (bpy= bipyridine, Cp*=1,2,3,4,5
      pentamethylcyclopentadienyl) containing differently substituted bipyridine
      ligands were synthesized and characterized. Cyclic voltammetry (CV) of the
      complexes in Ar-saturated acetonitrile solutions showed that the redox behavior
      of the complexes could be fine tuned by the electronic properties of the
      substituted bipyridine ligands. Further CV in CO2 -saturated MeCN/H2 O (9:1, v/v)
      solutions showed catalytic currents for CO2 reduction. In controlled potential
      electrolysis experiments (MeCN/MeOH (1:1, v/v), Eapp =-1.80 V vs Ag/AgCl), all of
      the complexes showed moderate activity in the electrocatalytic reduction of CO2
      with good stability over at least 15 hours. This electrocatalytic process was
      selective toward formic acid, with only traces of dihydrogen or carbon monoxide
      and occasionally formaldehyde as byproducts. However, the turnover frequencies
      and current efficiencies were quite low. No direct correlation between the redox
      potentials of the complexes and their catalytic activity was observed.

PMID- 25756196
TI  - Role of Mn content on the electrochemical properties of nickel-rich layered
      LiNi(0.8-x)Co(0.1)Mn(0.1+x)O2 (0.0 <= x <= 0.08) cathodes for lithium-ion
      batteries.
AB  - Ni-rich layered oxides (Ni content >60%) are promising cathode candidates for Li
      ion batteries because of their high discharge capacity, high energy density, and
      low cost. However, fast capacity fading, poor thermal stability, and sensitivity
      to the ambient moisture still plague their mass application. In this work, we
      systematically investigate the effects of Mn content on the structure,
      morphology, electrochemical performance, and thermal stability of the Ni-rich
      cathode materials LiNi(0.8-x)Co(0.1)Mn(0.1+x)O2 (0.0 <= x <= 0.08). It is
      demonstrated that with the increase in Mn content and decrease in Ni content, the
      cycling stability of LiNi(0.8-x)Co(0.1)Mn(0.1+x)O2 to a cutoff charge voltage of
      4.5 V is significantly improved. The high-Mn-content electrode
      LiNi(0.72)Co(0.10)Mn(0.18)O2 shows a capacity retention of 85.7% after 100 cycles
      at a 0.2 C rate at room temperature, much higher than those of the lower Mn
      content samples LiNi(0.80)Co(0.10)Mn(0.10)O2 (64.0%) and
      LiNi(0.76)Co(0.10)Mn(0.14)O2 (72.9%). The improved capacity retention of the high
      Mn-content electrode LiNi(0.72)Co(0.10)Mn(0.18)O2 is due to the stabilization of
      the electrode/electrolyte interface, as evidenced by the lower solid-electrolyte
      interphase (SEI) resistance and charge-transfer resistance. Furthermore, with the
      increase in Mn content and decrease in Ni content, the thermal stability of the
      Ni-rich cathode is also remarkably enhanced.

PMID- 25756195
TI  - Multilayered HIV-1 gag-specific T-cell responses contribute to slow progression
      in HLA-A*30-B*13-C*06-positive patients.
AB  - OBJECTIVE: The HLA-A30-B13-C06 haplotype is reported to be associated with slow
      disease progression in the HIV-1-infected Northern Han Chinese population, but
      the mechanism remains unknown. DESIGN: Gag-specific T-cell responses and gag
      sequencing were performed in nine B' clade HIV-1-infected HLA-A30-B13-C06
      positive slow progressors to understand HLA-associated viral control. METHODS:
      Interferon-gamma ELISPOT assays were performed to determine the Gag-specific T
      cell responses and cross-reactivity to variant peptides. Longitudinal HIV-1 gag
      sequencing was performed at the clonal level. RESULTS: The overlapping peptides
      (OLP)-48: RQANFLGKIWPSHKGRPGNF (RL42 Gag434-453); OLP-2: GQLDRWEKIRLRPGGKKKYR
      (RL42 Gag11-30); OLP-15: VQNLQGQMVHQPISPRTLNA (RL42 Gag135-154) and OLP-16:
      HQPISPRTLNAWVKVVEEKA (RL42 Gag144-163) were dominant in HLA-A30-B13-C06-positive
      patients. A new epitope [HQPISPRTL (Gag144-152, HL9)] within OLP-15 and OLP-16
      was identified. Results showed that strong cross-reactive responses to multiple
      immunodominant peptides were associated with better clinical outcomes. In
      addition, efficient cross-recognition of HL9 autologous variants developed in
      patients was associated with high CD4 T-cell counts. However, two patients who
      had developed mutations to their dominant responses during the follow-up
      experienced decrease in CD4 T-cell counts. It appears that Gag-specific T-cell
      responses against one or more unmutated epitopes or cross-recognition of
      autologous epitope variants contribute to slow disease progression in HLA-A30-B13
      C06-positive patients. CONCLUSION: We conclude that a single 'appropriate' Gag
      specific T-cell response appears to be sufficient to protect patients from
      disease progression. HLA-A30-B13-C06-positive individuals benefited from having a
      choice of numerous immunodominant gag epitopes for T cells to react. The study
      offers new insight for future design of T-cell-based HIV-1 vaccine.

PMID- 25756197
TI  - The Role of Socioeconomic Status and Health Care Access in Breast Cancer
      Screening Compliance Among Hispanics.
AB  - OBJECTIVES: Considerable disparities in breast cancer screening exist between
      Hispanic and non-Hispanic white (NHW) women. Identifying and quantifying the
      factors contributing to these racial-ethnic disparities can help shape
      interventions and policies aimed at reducing these disparities. This study, for
      the first time, identified and quantified individual-level sociodemographic and
      health-related factors that contribute to racial-ethnic disparities in breast
      cancer screening using the nonlinear Blinder-Oaxaca decomposition method.
      METHODS: Analysis of the retrospective pooled cross-sectional Medical Expenditure
      Panel Survey data from 2000 to 2010 was conducted. Women aged 40 years and older
      were included in the study. Logistic regressions were used to estimate racial
      ethnic disparities in breast cancer screening. Nonlinear Blinder-Oaxaca
      decomposition method was used to identify and quantify the contribution of each
      individual-level factor toward racial-ethnic disparities. RESULTS: Based on the
      unadjusted analyses, Hispanic women had lower odds of receiving mammogram
      screening (MS) (odds ratio [OR]: 0.74; 95% confidence interval [CI]: 0.69-0.80)
      and breast cancer screening (OR: 0.75; 95% CI: 0.70-0.81) as compared with NHW
      women. However, the relationship reversed in adjusted analyses, such that
      Hispanic women had higher odds of receiving MS (OR: 1.27; 95% CI: 1.16-1.40) and
      breast cancer screening (OR: 1.28; 95% CI: 1.17-1.40) as compared with NHW women.
      The Blinder-Oaxaca decomposition estimated that improving insurance status,
      access to care, education, and income will considerably increase screening rates
      among Hispanic women. CONCLUSIONS: The study projects that improving health care
      access and health education will considerably increase breast cancer screening
      compliance among Hispanic women. Policies like the Affordable Care Act, and
      patient navigation and health education interventions, might considerably reduce
      screening disparities in the Hispanic population.

PMID- 25756200
TI  - The processing of object identity information by women and men.
AB  - The study examined whether women excel at tasks which require processing the
      identity of objects information as has been suggested in the context of the well
      known object location memory task. In a computer-simulated task, university
      students were shown simulated indoor and outdoor house scenes. After studying a
      scene the students were presented with two images. One was the original image and
      the other a modified version in which one object was either rotated by ninety
      degrees or substituted with a similar looking object. The participants were asked
      to indicate the original image. The main finding was that no sex effect was
      obtained in this task. The female and male students did not differ on a verbal
      ability test, and their 2D:4D ratios were found to be comparable. 

PMID- 25756201
TI  - Synthesis of chiral 2,3-disubstituted 1,4-diazabicyclo[2.2.2]octane derivatives.
AB  - Racemic 2,3-diaryl-1,4-diazabicyclo[2.2.2]octane (DABCO) derivatives are
      synthesized from the readily accessible piperazines in 50-64% yield by
      cyclization using ethylene bromide, triethylamine, and KI at 80  degrees C. The
      enantiomerically enriched 2,3-diphenylpiperazine and the 2,3-bis(1
      naphthyl)piperazine derivatives are prepared by a resolution method using
      commercially available optically active acids, yielding the corresponding DABCO
      derivatives in 51-64% yield with up to 99% ee. This mild cyclization can also be
      applied to enantiopure camphanyldiamine derivatives, and the products are
      obtained in 72-86% yields. 

PMID- 25756202
TI  - Antimicrobial action of oleanolic acid on Listeria monocytogenes, Enterococcus
      faecium, and Enterococcus faecalis.
AB  - This study investigated the antimicrobial action of oleanolic acid against
      Listeria monocytogenes, Enterococcus faecium, and Enterococcus faecalis. To
      determine the cytotoxicity of oleanolic acid, HEp-2 cells were incubated with
      oleanolic acid at 37 degrees C. MICs (minimal inhibition concentrations) for L.
      monocytogenes, E. faecium, and E. faecalis were determined using two-fold
      microdilutions of oleanolic acid, and bacterial cell viability was then assessed
      by exposing the bacteria to oleanolic acid at 2 * MIC. To investigate the mode of
      antimicrobial action of oleanolic acid, we measured leakage of compounds
      absorbing at 280 nm, along with propidium iodide uptake. Scanning electron
      microscope (SEM) images were also analysed. The viability of HEp-2 cells
      decreased (P < 0.05) at oleanolic acid concentrations greater than 128 MUg mL(
      1). The MICs were 16-32 MUg mL(-1) for L. monocytogenes and 32-64 MUg mL(-1) for
      E. faecium and E. faecalis, and bacterial cell viability decreased (P < 0.05)
      about 3-4 log CFU mL(-1) after exposure to 2 * MIC of oleanolic acid. Leakage of
      280 nm absorbing materials and propidium iodide uptake was higher in oleanolic
      acid -treated cells than in the control. The cell membrane was damaged in
      oleanolic acid-treated cells, but the control group had intact cell membrane in
      SEM images. The results indicate that oleanolic acid can kill L. monocytogenes,
      E. faecium, and E. faecalis by destroying the bacterial cell membrane.

PMID- 25756203
TI  - Familial risks and estrogen receptor-positive breast cancer in Hong Kong Chinese
      women.
AB  - PURPOSE: The role of family history to the risk of breast cancer was analyzed by
      incorporating menopausal status in Hong Kong Chinese women, with a particular
      respect to the estrogen receptor-positive (ER+) type. METHODS: Seven hundred and
      forty seven breast cancer incident cases and 781 hospital controls who had
      completed information on family cancer history in first-degree relatives (nature
      father, mother, and siblings) were recruited. Odds ratio for breast cancer were
      calculated by unconditional multiple logistic regression, stratified by
      menopausal status (a surrogate of endogenous female sex hormone level and age)
      and type of relative affected with the disease. Further subgroup analysis by
      tumor type according to ER status was investigated. RESULTS: Altogether 52
      (6.96%) breast cancer cases and 23 (2.95%) controls was found that the patients'
      one or more first-degree relatives had a history of breast cancer, showing an
      adjusted odds ratio (OR) of 2.41 (95%CI: 1.45-4.02). An excess risk of breast
      cancer was restricted to the ER+ tumor (OR = 2.43, 95% CI: 1.38-4.28), with a
      relatively higher risk associated with an affected mother (OR = 3.97, 95%CI: 1.46
      10.79) than an affected sister (OR = 2.06, 95%CI: 1.07-3.97), while the relative
      risk was more prominent in the subgroup of pre-menopausal women. Compared with
      the breast cancer overall, the familial risks to the ER+ tumor increased
      progressively with the number of affected first-degree relatives. CONCLUSIONS:
      This study provides new insights on a relationship between family breast cancer
      history, menopausal status, and the ER+ breast cancer. A separate risk prediction
      model for ER+ tumor in Asian population is desired.

PMID- 25756204
TI  - Space-time analysis of testicular cancer clusters using residential histories: a
      case-control study in Denmark.
AB  - Though the etiology is largely unknown, testicular cancer incidence has seen
      recent significant increases in northern Europe and throughout many Western
      regions. The most common cancer in males under age 40, age period cohort models
      have posited exposures in the in utero environment or in early childhood as
      possible causes of increased risk of testicular cancer. Some of these factors may
      be tied to geography through being associated with behavioral, cultural,
      sociodemographic or built environment characteristics. If so, this could result
      in detectable geographic clusters of cases that could lead to hypotheses
      regarding environmental targets for intervention. Given a latency period between
      exposure to an environmental carcinogen and testicular cancer diagnosis, mobility
      histories are beneficial for spatial cluster analyses. Nearest-neighbor based Q
      statistics allow for the incorporation of changes in residency in spatial disease
      cluster detection. Using these methods, a space-time cluster analysis was
      conducted on a population-wide case-control population selected from the Danish
      Cancer Registry with mobility histories since 1971 extracted from the Danish
      Civil Registration System. Cases (N=3297) were diagnosed between 1991 and 2003,
      and two sets of controls (N=3297 for each set) matched on sex and date of birth
      were included in the study. We also examined spatial patterns in maternal
      residential history for those cases and controls born in 1971 or later (N= 589
      case-control pairs). Several small clusters were detected when aligning
      individuals by year prior to diagnosis, age at diagnosis and calendar year of
      diagnosis. However, the largest of these clusters contained only 2 statistically
      significant individuals at their center, and were not replicated in SaTScan
      spatial-only analyses which are less susceptible to multiple testing bias. We
      found little evidence of local clusters in residential histories of testicular
      cancer cases in this Danish population. 

PMID- 25756205
TI  - Using an adjusted Serfling regression model to improve the early warning at the
      arrival of peak timing of influenza in Beijing.
AB  - Serfling-type periodic regression models have been widely used to identify and
      analyse epidemic of influenza. In these approaches, the baseline is traditionally
      determined using cleaned historical non-epidemic data. However, we found that the
      previous exclusion of epidemic seasons was empirical, since year-year variations
      in the seasonal pattern of activity had been ignored. Therefore, excluding fixed
      'epidemic' months did not seem reasonable. We made some adjustments in the rule
      of epidemic-period removal to avoid potentially subjective definition of the
      start and end of epidemic periods. We fitted the baseline iteratively. Firstly,
      we established a Serfling regression model based on the actual observations
      without any removals. After that, instead of manually excluding a predefined
      'epidemic' period (the traditional method), we excluded observations which
      exceeded a calculated boundary. We then established Serfling regression once more
      using the cleaned data and excluded observations which exceeded a calculated
      boundary. We repeated this process until the R2 value stopped to increase. In
      addition, the definitions of the onset of influenza epidemic were heterogeneous,
      which might make it impossible to accurately evaluate the performance of
      alternative approaches. We then used this modified model to detect the peak
      timing of influenza instead of the onset of epidemic and compared this model with
      traditional Serfling models using observed weekly case counts of influenza-like
      illness (ILIs), in terms of sensitivity, specificity and lead time. A better
      performance was observed. In summary, we provide an adjusted Serfling model which
      may have improved performance over traditional models in early warning at arrival
      of peak timing of influenza. 

PMID- 25756206
TI  - Changes in von Willebrand factor level and von Willebrand activity with age in
      type 1 von Willebrand disease.
AB  - In a normal population, VWF plasma levels (VWF:Ag) and VWF activity (VWF:RCo)
      increase by approximately 0.17 and 0.15 IU mL(-1) per decade, but the influence
      of age is unknown in patients with type 1 von Willebrand disease (VWD). In a
      retrospective cohort study, the medical records of 31 type 1 VWD patients over
      the age of 30, who had been followed for >=5 years, were reviewed for baseline
      clinical data and previously performed VWF:Ag, VWF:RCo and factor VIII levels (
      FVIII: C). VWF multimer analysis was normal in 28/31 cases performed. Mean age at
      diagnosis was 33 (range 16-60 years), and duration of follow-up ranged from 5 to
      26 years (mean 11 years). Patients had 2-10 time points of VWD testing (mean of
      5.2). The mean VWF:Ag, VWF:RCo and FVIII: C at time of diagnosis were 0.44 IU mL(
      1) 0.34 IU mL(-1) and 0.75 IU mL(-1) . At last follow-up, the mean VWF:Ag,
      VWF:RCo and FVIII: C were significantly increased to 0.71 IU L(-1) , 0.56 IU mL(
      1) and 0.90 IU mL(-1) (P <= 0.001, <0.001, and 0.0081 respectively). Here 18/31
      patients had VWF:Ag, VWF:RCo and FVIII: C levels that increased into the normal
      range. The rate of change in VWF:Ag, VWF:RCo and FVIII was 0.30 IU mL(-1) (0.21
      0.39, CI 95%, P < 0.0001), 0.20 IU mL(-1) per decade (0.13-0.27, CI 95%, P =
      0.0001) and 0.20 IU mL(-1) (0.11-0.29, CI 95%, P = 0.0011). Patients with type 1
      VWD experience age-related increases to VWF:Ag and VWF:RCo which can result in
      normalization of VWF levels. Further studies are required to determine if the
      bleeding phenotype resolves with the increases in VWF:Ag and VWF:RCo levels.

PMID- 25756207
TI  - Biomass pyrolysis and combustion integral and differential reaction heats with
      temperatures using thermogravimetric analysis/differential scanning calorimetry.
AB  - Integral reaction heats of switchgrass, big bluestem, and corn stalks were
      determined using thermogravimetric analysis/differential scanning calorimetry
      (TGA/DSC). Iso-conversion differential reaction heats using TGA/DSC pyrolysis and
      combustion of biomass were not available, despite reports available on heats
      required and released. A concept of iso-conversion differential reaction heats
      was used to determine the differential reaction heats of each thermal
      characteristics segment of these materials. Results showed that the integral
      reaction heats were endothermic from 30 to 700 degrees C for pyrolysis of
      switchgrass and big bluestem, but they were exothermic for corn stalks prior to
      587 degrees C. However, the integral reaction heats for combustion of the
      materials followed an endothermic to exothermic transition. The differential
      reaction heats of switchgrass pyrolysis were predominantly endothermic in the
      fraction of mass loss (0.0536-0.975), and were exothermic for corn stalks (0.0885
      0.850) and big bluestem (0.736-0.919). Study results provided better insight into
      biomass thermal mechanism. 

PMID- 25756209
TI  - Development and validation of an ultra-high performance liquid chromatography
      tandem mass spectrometry method to measure creatinine in human urine.
AB  - Despite decades of creatinine measurement in biological fluids using a large
      variety of analytical methods, an accurate determination of this compound remains
      challenging. Especially with the novel trend to assess biomarkers on large sample
      sets preserved in biobanks, a simple and fast method that could cope with both a
      high sample throughput and a low volume of sample is still of interest. In answer
      to these challenges, a fast and accurate ultra-high performance liquid
      chromatography-tandem mass spectrometry (UHPLC-MS/MS) method was developed to
      measure creatinine in small volumes of human urine. In this method, urine samples
      are simply diluted with a basic mobile phase and injected directly under positive
      electrospray ionization (ESI) conditions, without further purification steps. The
      combination of an important diluting factor (10(4) times) due to the use of a
      very sensitive triple quadrupole mass spectrometer (XEVO TQ) and the addition of
      creatinine-d3 as internal standard completely eliminates matrix effects coming
      from the urine. The method was validated in-house in 2012 according to the EMA
      guideline on bioanalytical method validation using Certified Reference samples
      from the German External Quality Assessment Scheme (G-Equas) proficiency test.
      All obtained results for accuracy and recovery are within the authorized
      tolerance ranges defined by G-Equas. The method is linear between 0 and 5 g/L,
      with LOD and LOQ of 5 * 10(-3) g/L and 10(-2) g/L, respectively. The
      repeatability (CV(r) = 1.03-2.07%) and intra-laboratory reproducibility (CV(RW) =
      1.97-2.40%) satisfy the EMA 2012 guideline. The validated method was firstly
      applied to perform the German G-Equas proficiency test rounds 51 and 53, in 2013
      and 2014, respectively. The obtained results were again all within the accepted
      tolerance ranges and very close to the reference values defined by the organizers
      of the proficiency test scheme, demonstrating an excellent accuracy of the
      developed method. The method was finally applied to measure the creatinine
      concentration in 210 urine samples, coming from 190 patients with a chronic
      kidney disease (CKD) and 20 healthy subjects. The obtained creatinine
      concentrations (ranging from 0.12 g/L up to 3.84 g/L) were compared, by means of
      a Passing Bablok regression, with the creatinine contents obtained for the same
      samples measured using a traditional compensated Jaffe method. The UHPLC-MS/MS
      method described in this paper can be used to normalize the concentration of
      biomarkers in urine for the extent of dilution.

PMID- 25756208
TI  - Development and validation of a liquid chromatography tandem mass spectrometry
      assay for the quantitation of a protein therapeutic in cynomolgus monkey serum.
AB  - We have developed and fully validated a fast and simple LC-MS/MS assay to
      quantitate a therapeutic protein BMS-A in cynomolgus monkey serum. Prior to
      trypsin digestion, a recently reported sample pretreatment method was applied to
      remove more than 95% of the total serum albumin and denature the proteins in the
      serum sample. The pretreatment procedure simplified the biological sample prior
      to digestion, improved digestion efficiency and reproducibility, and did not
      require reduction and alkylation. The denatured proteins were then digested with
      trypsin at 60  degrees C for 30 min and the tryptic peptides were
      chromatographically separated on an Acquity CSH column (2.1 mm * 50 mm, 1.7 MUm)
      using gradient elution. One surrogate peptide was used for quantitation and
      another surrogate peptide was selected for confirmation. Two corresponding stable
      isotope labeled peptides were used to compensate variations during LC-MS
      detection. The linear analytical range of the assay was 0.50-500 MUg/mL. The
      accuracy (%Dev) was within +/- 5.4% and the total assay variation (%CV) was less
      than 12.0% for sample analysis. The validated method demonstrated good accuracy
      and precision and the application of the innovative albumin removal sample
      pretreatment method improved both assay sensitivity and robustness. The assay has
      been applied to a cynomolgus monkey toxicology study and the serum sample
      concentration data were in good agreement with data generated using a
      quantitative ligand-binding assay (LBA). The use of a confirmatory peptide, in
      addition to the quantitation peptide, ensured the integrity of the drug
      concentrations measured by the method.

PMID- 25756210
TI  - Association Between Functional Polymorphisms of DNA Double-Strand Breaks in
      Repair Genes XRCC5, XRCC6 and XRCC7 with the Risk of Systemic Lupus Erythematosus
      in South East Iran.
AB  - DNA repair is reduced in patients suffering from systemic lupus erythematosus
      (SLE), and it can induce the production of autoreactive antibodies due to the
      accumulation of DNA damage and nucleoprotein that produce immunogenic antigens.
      The accumulations of anti-Ku and DNA-PKcs antibodies, which are involved in
      nonhomologous DNA end joining pathway, have been detected in SLE patients. The
      present study was designed to evaluate the association of XRCC5, XRCC6, and XRCC7
      polymorphisms with SLE susceptibility. Polymerase chain reaction (PCR) was
      performed to genotype 163 SLE patients and 180 healthy controls for the XRCC5
      variable number of tandem repeat (VNTR) polymorphism. The genotype analysis of
      XRCC6-61C>G and XRCC7 6721G>T polymorphisms was performed using the polymerase
      chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique.
      There was a significant association between XRCC5 VNTR, XRCC7 6721G>T
      polymorphisms and risk of SLE development. Notably, the frequency of XRCC5 VNTR
      0R allele and genotypes with 2R allele was greatly enhanced in SLE patients with
      Malar rash (p=0.032 and p=0.024, respectively). Moreover, a higher frequency of
      genotypes with the XRCC5 VNTR 2R allele was observed in SLE patients with a
      positive antinuclear antibody (ANA) test (p=0.03). The present study shows an
      association between the XRCC5 VNTR, XRCC7 6721G>T polymorphisms and SLE. These
      polymorphisms might be genetic risk factors for SLE susceptibility and some SLE
      manifestations in the population southeast of Iran.

PMID- 25756211
TI  - Solvent-free ball-milling subcomponent synthesis of metallosupramolecular
      complexes.
AB  - Subcomponent self-assembly from components A, B, C, D, and Fe(2+) under solvent
      free conditions by self-sorting leads to the construction of three structurally
      different metallosupramolecular iron(II) complexes. Under carefully selected ball
      milling conditions, tetranuclear [Fe4 (AD2 )6 ](4-) 22-component cage 1,
      dinuclear [Fe2 (BD2 )3 ](2-) 11-component helicate 2, and 5-component mononuclear
      [Fe(CD3 )](2+) complex 3 were prepared simultaneously in a one-pot reaction from
      38 components. Through subcomponent substitution reaction by adding subcomponent
      B, the [Fe4 (AD2 )6 ](4-) cage converts quantitatively to the [Fe2 (BD2 )3 ](2-)
      helicate, which, in turn, upon addition of subcomponent C, transforms to [Fe(CD3
      )](2+) , following the hierarchical preference based on the thermodynamic
      stability of the complexes. 

PMID- 25756212
TI  - Characterizing tropical tree species growth strategies: learning from inter
      individual variability and scale invariance.
AB  - Understanding how tropical tree species differ in their growth strategies is
      critical to predict forest dynamics and assess species coexistence. Although tree
      growth is highly variable in tropical forests, species maximum growth is often
      considered as a major axis synthesizing species strategies, with fast-growing
      pioneer and slow-growing shade tolerant species as emblematic representatives. We
      used a hierarchical linear mixed model and 21-years long tree diameter increment
      series in a monsoon forest of the Western Ghats, India, to characterize species
      growth strategies and question whether maximum growth summarizes these
      strategies. We quantified both species responses to biotic and abiotic factors
      and individual tree effects unexplained by these factors. Growth responses to
      competition and tree size appeared highly variable among species which led to
      reversals in performance ranking along those two gradients. However, species
      specific responses largely overlapped due to large unexplained variability
      resulting mostly from inter-individual growth differences consistent over time.
      On average one-third of the variability captured by our model was explained by
      covariates. This emphasizes the high dimensionality of the tree growth process,
      i.e. the fact that trees differ in many dimensions (genetics, life history)
      influencing their growth response to environmental gradients, some being
      unmeasured or unmeasurable. In addition, intraspecific variability increased as a
      power function of species maximum growth partly as a result of higher absolute
      responses of fast-growing species to competition and tree size. However,
      covariates explained on average the same proportion of intraspecific variability
      for slow- and fast-growing species, which showed the same range of relative
      responses to competition and tree size. These results reflect a scale invariance
      of the growth process, underlining that slow- and fast-growing species exhibit
      the same range of growth strategies. 

PMID- 25756213
TI  - Reasons why people change their alcohol consumption in later life: findings from
      the Whitehall II Cohort Study.
AB  - PURPOSE: Harmful alcohol consumption among the ageing population is an important
      public health issue. Very few studies ask drinkers why they change their
      consumption in later life. The aim of this paper was to determine whether a group
      of people aged over 60 years increased or decreased their alcohol consumption
      over the past decade and to determine the reasons for their change. We also
      examined whether the responses varied by age, sex and socio-economic position
      (SEP). SUBJECTS AND METHODS: Data were taken from 6,011 participants (4,310 men,
      1,701 women, age range 61 to 85 years) who completed questionnaires at phase 11
      (2012-2013) of the Whitehall II Cohort Study. RESULTS: Over half the study
      members reported a change in alcohol consumption over the past decade (40%
      decreased, 11% increased). The most common reasons given for decreases were as a
      health precaution and fewer social occasions. Common reasons for increases were
      more social occasions and fewer responsibilities. The lowest SEP group was less
      likely to increase consumption compared to high SEP (RR 0.57, 95% CI 0.40 to
      0.81). Women were more likely to increase consumption in response to
      stress/depression than men (RR1.53, 95% CI 1.04 to 2.25). Compared to high SEP,
      the lowest SEP group was less likely to reduce as a health precaution (RR 0.61,
      95% CI 0.38 to 0.76). CONCLUSIONS: Alcohol consumption in late life is not fixed.
      Reasons for change vary by age, sex and SEP. Such information could be used to
      tailor intervention strategies to reduce harmful consumption.

PMID- 25756214
TI  - HIV treatment-as-prevention research: authors' reply.
AB  - Till Barnighausen and colleagues respond to comments by the HPTN 071 (PopART)
      Study Team, noting the distinction between the different HIV prevention questions
      the trial will attempt to answer. 

PMID- 25756217
TI  - High-throughput characterization of small and large molecules using only a matrix
      and the vacuum of a mass spectrometer.
AB  - Matrix assisted ionization vacuum (MAIV) rapidly generates gas-phase analyte ions
      from subliming solid-phase matrix:analyte crystals for analysis by mass
      spectrometry (MS). Ionization from the solid-phase allows the use of a variety of
      surfaces for introducing matrix:analyte samples to the vacuum of a mass
      spectrometer, including common laboratory materials, such as disposable pipet
      tips, filter paper, tooth picks, and nylon mesh. MAIV is shown here to be capable
      of analyses as fast as 3 s per sample with achievable sensitivities in the low
      femtomole range. MAIV-MS coupled with ion mobility spectrometry (IMS)-MS and
      tandem mass spectrometry (MS/MS) is shown to be especially powerful for analysis
      and characterization of a wide range of molecules ranging from small molecules
      such as drugs and metabolites (~300 Da) to intact proteins (25.6 kDa). Automated
      sample introduction is demonstrated on two different commercial mass
      spectrometers using a programmable XYZ stage. A MAIV high-throughput nontargeted
      MS(E) approach is also demonstrated utilizing IMS for rapid characterization of
      small molecules and peptides from standard solutions, as well as drug spiked
      human urine. 

PMID- 25756218
TI  - Young people are drinking less: it is time to find out why.

PMID- 25756216
TI  - Silica encapsulation of ferrimagnetic zinc ferrite nanocubes enabled by layer-by
      layer polyelectrolyte deposition.
AB  - Stable suspensions of magnetic nanoparticles (MNPs) with large magnetic moment,
      m, per particle have tremendous utility in a wide range of biological
      applications. However, because of the strong magnetic coupling interactions often
      present in these systems, it is challenging to stabilize individual, high-moment,
      ferro- and ferrimagnetic nanoparticles. A novel approach to encapsulate large,
      that is, >100 nm, ferrimagnetic zinc ferrite nanocubes (ZFNCs) with silica after
      an intermediary layer-by-layer polyelectrolyte deposition step is described in
      this paper. The seed ZFNCs are uniform in shape and size and have high saturation
      mass magnetic moment (sigma(s) ~100 emu/g, m ~ 4 * 10(-13) emu/particle at 150
      Oe). For the MNP system described within, successful silica encapsulation and
      creation of discrete ZFNCs were realized only after depositing polyelectrolyte
      multilayers composed of alternating polyallylamine and polystyrenesulfonate.
      Without the intermediary polyelectrolyte layers, magnetic dipole-dipole
      interactions led to the formation of linearly chained ZFNCs embedded in a silica
      matrix. Characterization of particle samples was performed by electron
      microscopy, energy-dispersive X-ray spectroscopy, infrared spectroscopy, powder X
      ray diffraction, dynamic light scattering (hydrodynamic size and zeta-potential),
      and vibrating sample magnetometry. The results of these characterizations, which
      were performed after each of the synthetic steps, and synthetic details are
      presented.

PMID- 25756215
TI  - Molecular phylogeny and biogeographic diversification of linnaeoideae
      (caprifoliaceae s. L.) disjunctly distributed in Eurasia, North America and
      Mexico.
AB  - Linnaeoideae is a small subfamily of erect or creeping shrubs to small trees in
      Caprifoliaceae that exhibits a wide disjunct distribution in Eurasia, North
      America and Mexico. Most taxa of the subfamily occur in eastern Asia and Mexico
      but the monospecific genus Linnaea has a circumboreal to north temperate
      distribution. In this study, we conducted phylogenetic and biogeographic analyses
      for Linnaeoideae and its close relatives based on sequences of the nuclear
      ribosomal ITS and nine plastid (rbcL, trnS-G, matK, trnL-F, ndhA, trnD-psbM, petB
      D, trnL-rpl32 and trnH-psbA) markers. Our results support that Linnaeoideae is
      monophyletic, consisting of four eastern Asian lineages (Abelia, Diabelia,
      Dipelta and Kolkwitzia), the Mexican Vesalea, and Linnaea. The Mexican Vesalea
      was formerly placed in Abelia, but it did not form a clade with the eastern Asian
      Abelia; instead Vesalea and Linnaea are sisters. The divergence time between the
      eastern Asian lineages and the Mexican Vesalea plus the Linnaea clade was dated
      to be 50.86 Ma, with a 95% highest posterior density of 42.8 Ma (middle Eocene)
      to 60.19 Ma (early Paleocene) using the Bayesian relaxed clock estimation.
      Reconstructed ancestral areas indicated that the common ancestor of Linnaea plus
      Vesalea may have been widespread in eastern Asia and Mexico or originated in
      eastern Asia during the Eocene and likely migrated across continents in the
      Northern Hemisphere via the North Atlantic Land Bridges or the Bering Land
      Bridge. The Qinling Mountains of eastern Asia are the modern-day center of
      diversity of Kolkwitzia-Dipelta-Diabelia clade. The Diabeliaclade became highly
      diversified in Japan and eastern China. Populations of Diabelia serrata in Japan
      and eastern China were found to be genetically identical in this study,
      suggesting a recent disjunction across the East China Sea, following the last
      glacial event. 

PMID- 25756219
TI  - Variability of PlayerLoad, Bowling Velocity, and Performance Execution in Fast
      Bowlers Across Repeated Bowling Spells.
AB  - PURPOSE: The use of wearable microtechnology to monitor the external load of fast
      bowling is challenged by the inherent variability of bowling techniques between
      bowlers. This study assessed the between-bowlers variability in PlayerLoad,
      bowling velocity, and performance execution across repeated bowling spells.
      METHODS: Seven national-level fast bowlers completed two 6-over bowling spells at
      a batter during a competitive training session. Key dependent variables were
      PlayerLoad calculated with a MinimaxX microtechnology unit, ball velocity, and
      bowling execution based on a predetermined bowling strategy for each ball bowled.
      The between-bowlers coefficient of variation (CV), repeated-measures ANOVA, and
      smallest worthwhile change were calculated over the 2 repeated 6-over bowling
      spells and explored across 12-over, 6-over, and 3-over bowling segments. RESULTS:
      From the sum of 6 consecutive balls, the between-bowlers CV for relative peak
      PlayerLoad was 1.2% over the 12-over bowling spell (P = .15). During this 12-over
      period, bowling-execution (P = .43) scores and ball-velocity (P = .31) CVs were
      calculated as 46.0% and 0.4%, respectively. CONCLUSIONS: PlayerLoad was found to
      be stable across the repeated bowling spells in the fast-bowling cohort. Measures
      of variability and change across the repeated bowling spells were consistent with
      the performance measure of ball velocity. The stability of PlayerLoad improved
      when assessed relative to the individual's peak PlayerLoad. Only bowling
      execution measures were found to have high variability across the repeated
      bowling spells. Player- Load provides a stable measure of external workload
      between fast bowlers.

PMID- 25756221
TI  - Commentary: Epidemiology in the era of big data.
AB  - Big Data has increasingly been promoted as a revolutionary development in the
      future of science, including epidemiology. However, the definition and
      implications of Big Data for epidemiology remain unclear. We here provide a
      working definition of Big Data predicated on the so-called "three V's": variety,
      volume, and velocity. From this definition, we argue that Big Data has
      evolutionary and revolutionary implications for identifying and intervening on
      the determinants of population health. We suggest that as more sources of diverse
      data become publicly available, the ability to combine and refine these data to
      yield valid answers to epidemiologic questions will be invaluable. We conclude
      that while epidemiology as practiced today will continue to be practiced in the
      Big Data future, a component of our field's future value lies in integrating
      subject matter knowledge with increased technical savvy. Our training programs
      and our visions for future public health interventions should reflect this
      future.

PMID- 25756222
TI  - Enhanced detection of broadband incoherent light with nanoridge plasmonics.
AB  - Emerging photonic integrated circuit technologies require integrative
      functionality at ultrahigh speed and dimensional compatibility with ultrasmall
      electronics. Plasmonics offers a promise of addressing these challenges with
      novel nanophotonic approaches for on-chip information processing or sensing
      applications. Short communication range and strong light-matter interaction
      enabled by on-chip plasmonics allow us to extend beyond a conventional approach
      of integrating coherent and narrowband light source. Such hybrid electronic and
      photonic interconnection desires a on-chip photodetector that is highly
      responsive to broadband incoherent light, yet provides elegant design for
      nanoscale integration. Here we demonstrate an ultracompact broadband
      photodetection with greatly enhanced photoresponsivity using plasmonic nanoridge
      geometry. The nanoridge photodetector confines a wide spectrum of electromagnetic
      energy in a nanostructure through the excitation of multiple plasmons, which thus
      enables the detection of weak and broadband light. With nanoscale design,
      material, and dimensional compatibility for the integration, the nanoridge
      photodetector opens up a new possibility of highly sensitive on-chip
      photodetection for future integrated circuits and sensing applications. 

PMID- 25756220
TI  - Drier air, lower temperatures, and triggering of paroxysmal atrial fibrillation.
AB  - BACKGROUND: The few previous studies on the onset of paroxysmal atrial
      fibrillation and meteorologic conditions have focused on outdoor temperature and
      hospital admissions, but hospital admissions are a crude indicator of atrial
      fibrillation incidence, and studies have found other weather measures in addition
      to temperature to be associated with cardiovascular outcomes. METHODS: Two
      hundred patients with dual chamber implantable cardioverter-defibrillators were
      enrolled and followed prospectively from 2006 to 2010 for new onset episodes of
      atrial fibrillation. The date and time of arrhythmia episodes documented by the
      implanted cardioverter-defibrillators were linked to meteorologic data and
      examined using a case-crossover analysis. We evaluated associations with outdoor
      temperature, apparent temperature, air pressure, and three measures of humidity
      (relative humidity, dew point, and absolute humidity). RESULTS: Of the 200
      enrolled patients, 49 patients experienced 328 atrial fibrillation episodes
      lasting >=30 seconds. Lower temperatures in the prior 48 hours were positively
      associated with atrial fibrillation. Lower absolute humidity (ie, drier air) had
      the strongest and most consistent association: each 0.5 g/m decrease in the prior
      24 hours increased the odds of atrial fibrillation by 4% (95% confidence interval
      [CI]: 0%, 7%) and by 5% (95% CI: 2%, 8%) for exposure in the prior 2 hours.
      Results were similar for dew point but slightly weaker. CONCLUSIONS: Recent
      exposure to drier air and lower temperatures were associated with the onset of
      atrial fibrillation among patients with known cardiac disease, supporting the
      hypothesis that meteorologic conditions trigger acute cardiovascular episodes.

PMID- 25756223
TI  - Discrepancies in the normative neonatal blood pressure reference ranges.
AB  - Numerous normative blood pressure (BP) reference ranges with considerable
      variation in the data have been published for neonates. This poses unique
      challenges for the definition and management of BP abnormalities in neonates. The
      aim of this study was to investigate the factors that have led to varying
      normative BP reference ranges in the studies conducted to date and to discuss
      potential study designs that would help better define the normative data. An
      electronic literature search was performed in 'PubMed' for articles published in
      English between January 1965 and February 2014 related to neonatal BP reference
      ranges. Common limitations found in the published studies included small sample
      sizes, combined use of oscillometric and intra-arterial BP measurements, lack of
      consideration of potentially influential factors such as postconception age,
      daily weight and medications, and use of data from individuals with wide ranges
      of gestational age, birth weight, and postconception age. Inconsistencies in the
      published neonatal BP reference ranges are likely due to a combination of factors
      related to study design. Attention to these issues should be considered when
      designing future multicenter studies on this topic. 

PMID- 25756224
TI  - Endo-beta-1,4-glucanases impact plant cell wall development by influencing
      cellulose crystallization.
AB  - Cell walls are vital to the normal growth and development of plants as they
      protect the protoplast and provide rigidity to the stem. Here, two poplar and
      Arabidopsis orthologous endoglucanases, which have been proposed to play a role
      in secondary cell wall development, were examined. The class B endoglucanases,
      PtGH9B5 and AtGH9B5, are secreted enzymes that have a predicted
      glycosylphosphatidylinositol anchor, while the class C endoglucanases, PtGH9C2
      and AtGH9C2, are also predicted to be secreted but instead contain a carbohydrate
      binding module. The poplar endoglucanases were expressed in Arabidopsis using
      both a 35S promoter and the Arabidopsis secondary cell wall-specific CesA8
      promoter. Additionally, Arabidopsis t-DNA insertion lines and an RNAi construct
      was created to downregulate AtGH9C2 in Arabidopsis. All of the plant lines were
      examined for changes in cell morphology and patterning, growth and development,
      cell wall crystallinity, microfibril angle, and proportion of cell wall
      carbohydrates. Misregulation of PtGH9B5/AtGH9B5 resulted in changes in xylose
      content, while misregulation of PtGH9C2/AtGH9C2 resulted in changes in
      crystallinity, which was inversely correlated with changes in plant height and
      rosette diameter. Together, these results suggest that these endoglucanases
      affect secondary cell wall development by contributing to the cell wall
      crystallization process. 

PMID- 25756225
TI  - Factors Affecting the Branching Ratio of Photodissociation: Thiophenol Studied
      through Quantum Wavepacket Dynamics.
AB  - The photodissociation dynamics of thiophenol (PhSH) excited to the 1(1) pipi*
      state was investigated by time-dependent quantum wavepacket propagation within
      two-dimensional (2D) space consisting of the S-H bond and -SH torsion. We
      systematically studied the dependence of the branching ratio (A/X(~)) between the
      two electronic states of the phenylthiyl radical (PhS(.) ) on several factors of
      the 2D potential energy surfaces (PESs). The effect of a reduced initial barrier
      to the first pipi*/pisigma* conical intersection (CI) was found to be marginal,
      whereas the effects of a reduced torsional barrier of -SH on the excited pipi*
      state and the mitigated slope of the pisigma* PES between the first
      (pipi*/pisigma*) and the second (pisigma*/S0 ) CIs were noticeable. The effect of
      the slope on the branching ratio has never been previously noticed. It was shown
      that the branching ratio can be sufficiently above unity without pre-excitation
      of the torsion mode of -SH, which has been assumed so far.

PMID- 25756226
TI  - Direct measurement of the isomerization barrier of the isolated retinal
      chromophore.
AB  - Isomerizations of the retinal chromophore were investigated using the IMS-IMS
      technique. Four different structural features of the chromophore were observed,
      isolated, excited collisionally, and the resulting isomer and fragment
      distributions were measured. By establishing the threshold activation voltages
      for isomerization for each of the reaction pathways, and by measuring the
      threshold activation voltage for fragmentation, the relative energies of the
      isomers as well as the energy barriers for isomerization were determined. The
      energy barrier for a single cis-trans isomerization is (0.64+/-0.05) eV, which is
      significantly lower than that observed for the reaction within opsin proteins. 

PMID- 25756227
TI  - Trophic transfer of gold nanoparticles from Euglena gracilis or Chlamydomonas
      reinhardtii to Daphnia magna.
AB  - Understanding the trophic transfer of nanoparticles (NPs) is important because
      NPs are small enough to easily penetrate into organisms. In this study, we
      evaluated the trophic transfer of gold NPs (AuNPs) within the aquatic food chain.
      We observed AuNPs transfer from 2 species of primary producers (Chlamydomonas
      reinhardtii or Euglena gracilis) to the primary consumer (Daphnia magna). Also,
      bioaccumulation of AuNPs in E. gracilis was higher than that in C. reinhardtii.
      The reasons for the difference in Au accumulation may be the physical structure
      of these organisms, and the surface area that is available for interaction with
      NPs. C. reinhardtii has a cell wall that may act as a barrier to the penetration
      of NPs. The size of E. gracilis is larger than that of C. reinhardtii. This study
      demonstrates the trophic transfer of AuNPs from a general producer to a consumer
      in an aquatic environment. 

PMID- 25756228
TI  - Long-term recovery of clutch size and egg shell quality of the pied flycatcher
      (Ficedula hypoleuca) in a metal polluted area.
AB  - We explored if breeding parameters and egg shell quality of an insectivorous
      passerine, pied flycatcher Ficedula hypoleuca, have fully recovered after c.a.
      99% decrease in dust emissions from a non-ferrous smelter in the course of the 23
      year study period. Some potentially important population characteristics
      (density, phenology, age) and environmental variables (habitat, inter-specific
      competition) were taken into account in the analysis. We found marked increase in
      reproductive parameters (egg shell quality, clutch size, hatchability, and
      fledgling number) in the metal polluted area especially in 1990's when metal-rich
      dust emissions from the smelter were markedly reduced. Still clutch sizes and
      fledgling numbers remain below the levels of the reference area. There is
      currently very little evidence of direct toxic effects of metals in our study
      population but full recovery of breeding parameters may not be reached until the
      full recovery of food chains, which is likely to be a slow process. 

PMID- 25756229
TI  - Intradermal testing after negative skin prick testing for patients with high
      suspicion of allergy.
AB  - BACKGROUND: Skin testing is a widely accepted method for identifying inhalant
      allergies. Intradermal (ID) testing is often performed after negative skin prick
      testing (SPT) when a practitioner has a high level of clinical suspicion for a
      particular allergen. METHODS: A retrospective chart review study was performed
      over a 5-year period in patients with negative SPT for airborne allergens who
      also underwent ID testing based on a high level of suspicion for clinical
      allergy. RESULTS: Eighty-seven patients had negative SPT and went on to receive
      an average of 7 ID tests per patient. A total of 592 ID tests were performed
      after negative SPT. Of these, 20.8% (123/592) had a positive ID result with
      negative SPT. The allergens with the greatest percentage of positive ID results
      with negative SPTs were dog, cat, D. farinae, and D. pteronyssinus (33.3%, 34.3%,
      39.4%, and 39.6%, respectively). The allergens least likely to test positive on
      ID testing after negative SPT were red maple, Cladosporium, and Alternaria (0%,
      6.3%, and 6.5%, respectively). CONCLUSION: Approximately 20% of all negative
      results on SPT will have a positive ID test, more likely for indoor allergens. If
      a high suspicion for allergy exists in a patient with a negative SPT result, it
      may be useful to proceed with ID testing. However, the clinical significance of a
      positive ID test after negative SPT still needs to be elucidated.

PMID- 25756230
TI  - Open-shell lanthanide(II+) or -(III+) complexes bearing sigma-silyl and silylene
      ligands: synthesis, structure, and bonding analysis.
AB  - Complexes featuring lanthanide (Ln)-Si bonds represent a highly neglected
      research area. Herein, we report a series of open-shell Ln(II+) and Ln(III+)
      complexes bearing sigma-bonded silyl and base-stabilized N-heterocyclic silylene
      (NHSi) ligands. The reactions of the Ln(III+) complexes Cp3Ln (Ln = Tm, Ho, Tb,
      Gd; Cp = cyclopentadienide) with the 18-crown-6 (18-cr-6)-stabilized 1,4
      oligosilanyl dianion [(18-cr-6)KSi(SiMe3)2SiMe2SiMe2Si(SiMe3)2K(18-cr-6)] (1)
      selectively afford the corresponding metallacyclopentasilane salts
      [Cp2Ln({Si(SiMe3)2SiMe2}2)](-)[K2(18-cr-6)2Cp](+) [Ln = Tm (2a), Ho (2b), Tb
      (2c), Gd (2d)]. Complexes 2a-2d represent the first examples of structurally
      characterized Tm, Ho, Tb, and Gd complexes featuring Ln-Si bonds. Strikingly, the
      analogous reaction of 1 with the lighter element analogue Cp3Ce affords the
      acyclic product [Cp3CeSi(SiMe3)2SiMe2SiMe2Si(SiMe3)2-Cp3Ce](2-)2[K(18-cr-6)](+)
      (3) as the first example of a complex featuring a Ce-Si bond. In an alternative
      synthetic approach, the aryloxy-functionalized benzamidinato NHSi ligand Si(OC6H4
      2-tBu){(NtBu)2CPh} (4a) and the alkoxy analogue Si(OtBu){(NtBu)2CPh} (4b) were
      reacted with Cp*2Sm(OEt2), affording, by OEt2 elimination, the corresponding
      silylene complexes, both featuring Sm(II+) centers: Cp*2Sm <- :Si(O-C6H4-2
      tBu){(NtBu)2CPh} (6) and Cp*2Sm <- :Si(OtBu){(NtBu)2CPh} (5). Complexes 5 and 6
      are the first four-coordinate silylene complexes of any f-block element to date.
      All complexes were fully characterized by spectroscopic means and by single
      crystal X-ray diffraction analysis. In the series 2a-2d, a linear correlation was
      observed between the Ln-Si bond lengths and the covalent radii of the
      corresponding Ln metals. Moreover, in complexes 5 and 6, notably long Sm-Si bonds
      are observed, in accordance with a donor-acceptor interaction between Si and Sm
      [5, 3.4396(15) A; 6, 3.3142(18) A]. Density functional theory calculations were
      carried out for complexes 2a-2d, 5, and 6 to elucidate the bonding situation
      between the Ln(II+) or Ln(III+) centers and Si. In particular, a decrease in the
      Mayer bond order (MBO) of the Ln-Si bond is observed in the series 2a-2d in
      moving from the lighter to the heavier lanthanides (Tm = 0.53, Ho = 0.62, Tb =
      0.65, and Gd = 0.75), which might indicate decreasing covalency in the Ln-Si
      bond. In accordance with the long bond lengths observed experimentally in
      complexes 5 and 6, comparatively low MBOs were determined for both silylene
      complexes (5, 0.24; 6, 0.25) . 

PMID- 25756231
TI  - Slackline training and neuromuscular performance in seniors: A randomized
      controlled trial.
AB  - Slackline training (balancing on nylon ribbons) has been shown to improve
      neuromuscular performance in children and adults. Comparable studies in seniors
      are lacking. Thus, 32 seniors were randomly assigned [strata: age, gender,
      physical activity (PA)] to an intervention [INT; n = 16, age: 65 +/- 4 years, PA:
      9 +/- 5 h/week] or control [CON, n = 16, age: 63 +/- 4 years, PA: 8 +/- 4 h/week]
      group. Slackline training was given for 6 weeks (3 times per week, attendance
      97%). Static and slackline standing balance performance, force development, and
      maximal strength of the ankle muscles were assessed before and after slackline
      training. Muscle activity (lower limb and trunk) was recorded during balance
      testing. Moderate to large group * time interactions (0.02 < P < 0.04, 0.11 <
      etap (2)  < 0.17) in favor of INT were found for slackline standing times (INT:
      left, +278%, P = 0.02; right, +328%, P = 0.03; tandem, +94%, P = 0.007) and
      muscle activity during single-limb slackline standing [INT: right: rectus
      abdominis (RA), P = 0.003, -15%; multifidus (MF), P = 0.01, -15%; left: tibialis
      anterior (TIB), P = 0.03, -12%; soleus (SOL), P = 0.006, -18%; RA, P = 0.04, 
      11%; MF, P = 0.01, -16%; gastrocnemius medialis (GM), P = 0.02, -19%]. Static
      balance performance, ankle strength, and power were not affected. Slackline
      training induced large task-specific improvements of slackline standing
      performance accompanied with reductions of lower limb and trunk muscle activity.
      Transfer effects to static balance and strength measures seem limited.

PMID- 25756232
TI  - No evidence of purported lunar effect on hospital admission rates or birth rates.
AB  - BACKGROUND: Studies indicate that a fraction of nursing professionals believe in
      a "lunar effect"-a purported correlation between the phases of the Earth's moon
      and human affairs, such as birth rates, blood loss, or fertility. PURPOSE: This
      article addresses some of the methodological errors and cognitive biases that can
      explain the human tendency of perceiving a lunar effect where there is none.
      APPROACH: This article reviews basic standards of evidence and, using an example
      from the published literature, illustrates how disregarding these standards can
      lead to erroneous conclusions. FINDINGS: Roman, Soriano, Fuentes, Galvez, and
      Fernandez (2004) suggested that the number of hospital admissions related to
      gastrointestinal bleeding was somehow influenced by the phases of the Earth's
      moon. Specifically, the authors claimed that the rate of hospital admissions to
      their bleeding unit is higher during the full moon than at other times. Their
      report contains a number of methodological and statistical flaws that invalidate
      their conclusions. Reanalysis of their data with proper procedures shows no
      evidence that the full moon influences the rate of hospital admissions, a result
      that is consistent with numerous peer-reviewed studies and meta-analyses. A
      review of the literature shows that birth rates are also uncorrelated to lunar
      phases. CONCLUSIONS: Data collection and analysis shortcomings, as well as
      powerful cognitive biases, can lead to erroneous conclusions about the purported
      lunar effect on human affairs. Adherence to basic standards of evidence can help
      assess the validity of questionable beliefs.

PMID- 25756235
TI  - Lower placental telomere length may be attributed to maternal residential traffic
      exposure; a twin study.
AB  - BACKGROUND: High variation in telomere length between individuals is already
      present before birth and is as wide among newborns as in adults. Environmental
      exposures likely have an impact on this observation, but remain largely
      unidentified. We hypothesize that placental telomere length in twins is
      associated with residential traffic exposure, an important environmental source
      of free radicals that might accelerate aging. Next, we intend to unravel the
      nature-nurture contribution to placental telomere length by estimating the
      heritability of placental telomere length. METHODS: We measured the telomere
      length in placental tissues of 211 twins in the East Flanders Prospective Twin
      Survey. Maternal traffic exposure was determined using a geographic information
      system. Additionally, we estimated the relative importance of genetic and
      environmental sources of variance. RESULTS: In this twin study, a variation in
      telomere length in the placental tissue was mainly determined by the common
      environment. Maternal residential proximity to a major road was associated with
      placental telomere length: a doubling in the distance to the nearest major road
      was associated with a 5.32% (95% CI: 1.90 to 8.86%; p=0.003) longer placental
      telomere length at birth. In addition, an interquartile increase (22%) in
      maternal residential surrounding greenness (5 km buffer) was associated with an
      increase of 3.62% (95% CI: 0.20 to 7.15%; p=0.04) in placental telomere length.
      CONCLUSIONS: In conclusion, we showed that maternal residential proximity to
      traffic and lower residential surrounding greenness is associated with shorter
      placental telomere length at birth. This may explain a significant proportion of
      air pollution-related adverse health outcomes starting from early life, since
      shortened telomeres accelerate the progression of many diseases.

PMID- 25756236
TI  - Housing temperature-induced stress drives therapeutic resistance in murine tumour
      models through beta2-adrenergic receptor activation.
AB  - Cancer research relies heavily on murine models for evaluating the anti-tumour
      efficacy of therapies. Here we show that the sensitivity of several pancreatic
      tumour models to cytotoxic therapies is significantly increased when mice are
      housed at a thermoneutral ambient temperature of 30  degrees C compared with the
      standard temperature of 22  degrees C. Further, we find that baseline levels of
      norepinephrine as well as the levels of several anti-apoptotic molecules are
      elevated in tumours from mice housed at 22  degrees C. The sensitivity of tumours
      to cytotoxic therapies is also enhanced by administering a beta-adrenergic
      receptor antagonist to mice housed at 22  degrees C. These data demonstrate that
      standard housing causes a degree of cold stress sufficient to impact the
      signalling pathways related to tumour-cell survival and affect the outcome of pre
      clinical experiments. Furthermore, these data highlight the significant role of
      host physiological factors in regulating the sensitivity of tumours to therapy. 

PMID- 25756237
TI  - Serrated polyps and the risk of synchronous colorectal advanced neoplasia: a
      systematic review and meta-analysis.
AB  - OBJECTIVES: Serrated polyps of the colon comprise a heterogeneous group of
      lesions with distinct histological and malignant features. The presence of
      serrated polyps has been associated with synchronous advanced neoplasia, although
      the magnitude of this relationship is unclear. METHODS: Using studies identified
      from systematic literature search up to February 2014, we performed a systematic
      review and meta-analysis to estimate the pooled prevalence of serrated polyps and
      their association with synchronous advanced neoplasia. Random-effects models were
      used to combine estimates from heterogeneous studies, and odds ratios (ORs) with
      95% confidence intervals (CIs) were presented. RESULTS: Nine studies with 34,084
      participants were included. The mean age of subjects was 59.9+/-6.6 years and
      52.5% of the subjects were male. Pooled prevalence of serrated polyps was 15.6%
      (95% CI, 10.3-22.9%). The pooled OR of advanced neoplasia in individuals with
      serrated polyps was 2.05 (95% CI, 1.38-3.04). Pooled analysis showed that the
      presence of proximal serrated polyps (OR=2.77, 95% CI, 1.71-4.46) and large
      serrated polyps (OR=4.10, 95% CI, 2.69-6.26) was associated with an increased
      risk of synchronous advanced neoplasia. The pooled OR for advanced neoplasia in
      individuals with proximal and large serrated polyps was 3.35 (95% CI, 2.51-4.46).
      Considerable heterogeneity was observed in most analyses. CONCLUSIONS: Our meta
      analysis showed that serrated polyps are associated with a more than twofold
      increased risk of detection of synchronous advanced neoplasia. Individuals with
      proximal and large serrated polyps have the highest risk. These individuals
      deserve surveillance colonoscopy.

PMID- 25756238
TI  - Inflammatory bowel disease in immigrants to Canada and their children: a
      population-based cohort study.
AB  - OBJECTIVES: The risk of inflammatory bowel disease (IBD) contributed by the
      environment can be elucidated by assessing the risk in migrants from low
      prevalence to Western countries. The incidence of IBD in immigrants to Canada and
      their Canadian-born children was compared with nonimmigrants. METHODS: A
      population-based cohort of IBD patients derived from health administrative data
      was linked to immigration data to determine the standardized incidence of IBD in
      immigrants to Ontario, Canada, by region of birth between 1994 and 2010. The
      hazard contributed by younger age at immigration was determined. Incidence for
      Ontario-born children of immigrant mothers was compared with the children of
      nonimmigrants. RESULTS: In 2,144,660 immigrants, incidence of IBD was 7.3/100,000
      person-years compared with 23.9/100,000 in 12,036,921 nonimmigrants (incidence
      rate ratio (IRR) 0.34, 95% CI 0.26-0.44). Incidence was lowest risk in East
      Asians (IRR 0.14, 95% CI 0.11-0.18) and highest in Western Europeans/North
      Americans (IRR 0.59, 95% CI 0.46-0.75). Increased age at immigration was
      associated with decreased risk of IBD (HR 0.986, 95% CI 0.982-0.990), a 14%
      increased risk per younger decade of life at immigration. Children of immigrants
      from the Middle East/North Africa, South Asia, Sub-Saharan Africa, and North
      America/Western Europe had similar risk of IBD as children of nonimmigrants;
      however, the incidence remained lower among children of immigrants from other
      regions. CONCLUSIONS: Younger age at arrival to Canada increased the risk of IBD
      in immigrants. Canadian-born children of immigrants from some regions assumed the
      high Canadian incidence of IBD, indicating that the underlying risk is activated
      with earlier life exposure to the Canadian environment in certain groups.

PMID- 25756239
TI  - Lack of health insurance limits the benefits of hepatitis C virus screening:
      insights from the National Health and Nutrition Examination Hepatitis C follow-up
      study.
AB  - OBJECTIVES: Identifying barriers to access to hepatitis C virus (HCV) treatment
      among screen detected subjects is critical for any public health strategy aimed
      at controlling HCV infection in the general population. METHODS: Data from the
      National Health and Nutrition Examination Survey HCV Follow-up study from 2001 to
      2010 were used. Participants who tested positive for HCV were sent a letter
      informing them of their test results and advised to pursue further evaluation.
      Information on HCV transmission and its potential complications was also provided
      to all positive participants. These subjects were recontacted 6 months after
      notification to determine what action they had taken regarding the positive
      result. RESULTS: Of 38,025 participants, 502 tested positive for HCV infection,
      giving a prevalence of 1.3% (95% confidence interval (CI) 0.8%, 1.8%). A total of
      205 subjects participated in the 6-month follow-up interview. Those who could not
      be reached were more likely to be less educated, injecting drugs, and not to have
      health insurance. Half (50.2%) of the positive individuals were not aware of
      their status before notification. A total of 166 (81%) had pursued further
      evaluation. Only 18 (26.9%) received therapy. The main reason for not receiving
      treatment was high cost (19.4%). In adjusted analysis, the only barrier to
      pursuing downstream HCV care was the lack of health insurance (2.76, 95% CI 1.54,
      7.69; P=0.007). CONCLUSIONS: This study suggests that the lack of health
      insurance may attenuate the theoretical benefits of a screening program that
      identifies asymptomatic HCV-infected individuals who are less likely to pursue
      downstream care.

PMID- 25756240
TI  - Multi-center colonoscopy quality measurement utilizing natural language
      processing.
AB  - BACKGROUND: An accurate system for tracking of colonoscopy quality and
      surveillance intervals could improve the effectiveness and cost-effectiveness of
      colorectal cancer (CRC) screening and surveillance. The purpose of this study was
      to create and test such a system across multiple institutions utilizing natural
      language processing (NLP). METHODS: From 42,569 colonoscopies with pathology
      records from 13 centers, we randomly sampled 750 paired reports. We trained
      (n=250) and tested (n=500) an NLP-based program with 19 measurements that
      encompass colonoscopy quality measures and surveillance interval determination,
      using blinded, paired, annotated expert manual review as the reference standard.
      The remaining 41,819 nonannotated documents were processed through the NLP system
      without manual review to assess performance consistency. The primary outcome was
      system accuracy across the 19 measures. RESULTS: A total of 176 (23.5%) documents
      with 252 (1.8%) discrepant content points resulted from paired annotation. Error
      rate within the 500 test documents was 31.2% for NLP and 25.4% for the paired
      annotators (P=0.001). At the content point level within the test set, the error
      rate was 3.5% for NLP and 1.9% for the paired annotators (P=0.04). When eight
      vaguely worded documents were removed, 125 of 492 (25.4%) were incorrect by NLP
      and 104 of 492 (21.1%) by the initial annotator (P=0.07). Rates of pathologic
      findings calculated from NLP were similar to those calculated by annotation for
      the majority of measurements. Test set accuracy was 99.6% for CRC, 95% for
      advanced adenoma, 94.6% for nonadvanced adenoma, 99.8% for advanced sessile
      serrated polyps, 99.2% for nonadvanced sessile serrated polyps, 96.8% for large
      hyperplastic polyps, and 96.0% for small hyperplastic polyps. Lesion location
      showed high accuracy (87.0-99.8%). Accuracy for number of adenomas was 92%.
      CONCLUSIONS: NLP can accurately report adenoma detection rate and the components
      for determining guideline-adherent colonoscopy surveillance intervals across
      multiple sites that utilize different methods for reporting colonoscopy findings.

PMID- 25756242
TI  - Rapid Deployment Valve Implantation using the EDWARDS Intuity Valve System: A
      Word of Caution regarding Sizing in Calcified Sinotubular Junctions.
AB  - In aortic valve replacement, severe calcification of the sinotubular junction is
      a limitation in the application of the rapid deployment Edwards Intuity valve
      system. This is illustrated by a case presentation in which discrepancies of
      shape and diameter between sizer and valve mounted on the deployment system
      resulted in discarding the prosthesis and performing a biocomposite root
      replacement instead. Modification of the valve sizer will allow for safer sizing
      because the sizing process will mimic the implantation process more accurately. 

PMID- 25756241
TI  - Versatile, tannic acid-mediated surface PEGylation for marine antifouling
      applications.
AB  - In this study, we report a facile and versatile approach to the formation of
      marine antifouling surface coatings. The approach consists of a combined coating
      of polydopamine (pDA) and tannic acid (TA) and subsequent immobilization of
      polyethylene glycol (PEG) on solid substrates. TA coating of a pDA-coated surface
      was carried out using iron(III) coordination chemistry, and PEG was immobilized
      on the TA-coated surface via hydrogen bond formation. Stainless steel and nylon
      were successfully modified by this approach, and the resulting substrates were
      used for marine antifouling applications, in which diatom adhesion was
      significantly inhibited. Advantageously, this approach allowed marine antifouling
      coatings to be prepared by a simple immersion process under environmentally
      friendly conditions. 

PMID- 25756243
TI  - Predictors of Disease-free Survival and Recurrence in Patients with Resected
      Bronchial Carcinoid Tumors.
AB  - BACKGROUND: Bronchial carcinoids are characterized by neuroendocrine
      differentiation and have distinct biological behavior, recurrence patterns, and
      prognosis compared with adenocarcinomas or squamous cell carcinomas. Because of
      their often indolent nature, it has been suggested that routine postoperative
      imaging surveillance may not be warranted in the majority of patients. This study
      aims to define the factors that predict disease-free survival (DFS) and
      recurrence after resection of these tumors, with the goal of identifying high
      risk patients for whom image surveillance may be warranted. METHODS: We conducted
      a retrospective review of a prospective database to identify patients with
      completely resected bronchial carcinoid tumors. Surgical procedure, histology,
      pathological stage, follow-up, tumor recurrence, and survival were assessed.
      RESULTS: One hundred and forty-two patients were identified. Median age was 62
      years and the majority was women (106). Surgical procedures included 20 wedge
      resections, 10 segmentectomies, 99 lobectomies, 3 bilobectomies, 2
      pneumonectomies, 6 sleeve resections, and 2 bronchectomies. Pathologic stages
      included I (81%), II (10%), III (8%), and IV (1%). With a median follow-up of 31
      months, there were seven recurrences. The 5- and 10-year overall survival rates
      were 92% and 75% and DFS rates were 88% and 72%, respectively. There were 34
      patients with atypical carcinoids, and 6 (18%) developed recurrence, compared
      with 1 recurrence (1%) in the group of 108 patients with typical carcinoids (p =
      0.0008). For atypical carcinoid tumors, the 5- and 10-year DFS rates were 72% and
      32% versus 92% and 85% in typical carcinoid tumors (p = 0.001). Patients with
      more advanced tumor stage pT2-4 and pathologic N1/N2 nodal metastases had a
      significantly decreased 5- and 10-year DFS compared with those with early pT1
      stage (p = 0.029) or those without nodal disease (p = 0.043). Multivariate Cox
      regression analyses showed advancing age (p = 0.001), atypical histology (p =
      0.021), and advanced tumor stage (p = 0.047) were significant negative predictors
      for DFS. CONCLUSION: Long-term survival after resection of bronchial carcinoids
      is common, especially for patients with typical carcinoid tumors. DFS can be
      negatively influenced by atypical histology, advanced tumor, and nodal statuses.
      Efforts at postoperative image surveillance should target those patients with
      such high-risk factors.

PMID- 25756244
TI  - Environmental factors influencing the distribution of ammonifying and
      denitrifying bacteria and water qualities in 10 lakes and reservoirs of the
      Northeast, China.
AB  - This study presents seasonal and spatial variations of the ammonifying bacteria
      (AB) and denitrifying bacteria (DNB) and physicochemical parameters in 10 lakes
      and reservoirs in the northeast of China. Water samples were collected in winter
      (January), spring (March), summer (July) and fall (November) in 2011. The study
      revealed that physicochemical parameters such as pH, dissolved oxygen (DO), NH4
      (+) -N and nitrate as nitrogen were closely related with the distribution of AB
      and DNB. Seasonally, the levels of AB presents gradually upward trend from winter
      to summer, and declines in fall and DNB were higher in spring and fall than
      summer and lowest in winter. Spatially, the annual average of AB among 10 lakes
      and reservoirs showed insignificant difference (P > 0.05), for DNB, Udalianchi
      and Lianhuan Lake were lower than others (P < 0.05). Regression correlation
      analysis showed that the levels of AB and DNB had a close relationship with
      nitrogen nutrition. Three principal components were identified of total variances
      which are conditionally classified by the 'natural' factor (PC1) and 'nitrogen
      nutrients' (PC2, PC3). According the principal component scores, cluster analysis
      detected two distinct groups: (C1) mainly affected by nitrogen nutrients and (C2)
      natural environmental factors. 

PMID- 25756245
TI  - MALDI Mass Spectrometry Imaging of Lipids and Gene Expression Reveals Differences
      in Fatty Acid Metabolism between Follicular Compartments in Porcine Ovaries.
AB  - In mammals, oocytes develop inside the ovarian follicles; this process is
      strongly supported by the surrounding follicular environment consisting of
      cumulus, granulosa and theca cells, and follicular fluid. In the antral follicle,
      the final stages of oogenesis require large amounts of energy that is produced by
      follicular cells from substrates including glucose, amino acids and fatty acids
      (FAs). Since lipid metabolism plays an important role in acquiring oocyte
      developmental competence, the aim of this study was to investigate site
      specificity of lipid metabolism in ovaries by comparing lipid profiles and
      expression of FA metabolism-related genes in different ovarian compartments.
      Using MALDI Mass Spectrometry Imaging, images of porcine ovary sections were
      reconstructed from lipid ion signals for the first time. Cluster analysis of ion
      spectra revealed differences in spatial distribution of lipid species among
      ovarian compartments, notably between the follicles and interstitial tissue.
      Inside the follicles analysis differentiated follicular fluid, granulosa, theca
      and the oocyte-cumulus complex. Moreover, by transcript quantification using real
      time PCR, we showed that expression of five key genes in FA metabolism
      significantly varied between somatic follicular cells (theca, granulosa and
      cumulus) and the oocyte. In conclusion, lipid metabolism differs between ovarian
      and follicular compartments. 

PMID- 25756246
TI  - Recent advances in the analysis of macromolecular interactions using the matrix
      free method of sedimentation in the analytical ultracentrifuge.
AB  - Sedimentation in the analytical ultracentrifuge is a matrix free solution
      technique with no immobilisation, columns, or membranes required and can be used
      to study self-association and complex or "hetero"-interactions, stoichiometry,
      reversibility and interaction strength of a wide variety of macromolecular types
      and across a very large dynamic range (dissociation constants from 10-12 M to 10
      1 M). We extend an earlier review specifically highlighting advances in
      sedimentation velocity and sedimentation equilibrium in the analytical
      ultracentrifuge applied to protein interactions and mucoadhesion and to review
      recent applications in protein self-association (tetanus toxoid, agrin), protein
      like carbohydrate association (aminocelluloses), carbohydrate-protein
      interactions (polysaccharide-gliadin), nucleic-acid protein (G-duplexes), nucleic
      acid-carbohydrate (DNA-chitosan) and finally carbohydrate-carbohydrate (xanthan
      chitosan and a ternary polysaccharide complex) interactions. 

PMID- 25756249
TI  - Thiazolidinediones Inhibit Mouse Osteoblastic MC3T3-E1 Cell Proliferation in Part
      Through the Wnt Signaling Pathway.
AB  - BACKGROUND: Peroxisome proliferator-activated receptor gamma (PPARgamma) and Wnt
      play different roles in bone homeostasis. Thiazolidinediones are PPARgamma
      agonists that cause bone mineral density loss. This study investigated the
      relationship between PPARgamma and Wnt/beta-catenin signaling in mouse
      osteoblastic MC3T3-E1 cells. METHODS: MC3T3-E1 cells were treated with either
      pioglitazone (Pio) or rosiglitazone (Rosi), thiazolidinediones, for 24 hours at
      10 to 40-MUM concentrations. Recombinant mouse Wnt3a protein (50 ng/mL) for 6
      hours was also used to treat the 20-MUM Pio and Rosi pretreated cells. Cell
      proliferation was measured by MTT, and apoptosis with flow cytometry using
      annexin V/propidium iodide staining; reverse transcriptase-polymerase chain
      reaction measured mRNA expression levels of LRP5/6 (low-density lipoprotein
      related protein 5/6), glycogen synthase kinase 3beta (GSK3beta), TCF7L2
      (transcription factor 7-like 2), PPARgamma, and cyclin D1, and Western blots
      detected beta-catenin and p-GSK3beta proteins. RESULTS: Pioglitazone and Rosi
      decreased MC3T3-E1 cell viability by 28.07% and 18.14% at 20 MUM, respectively (P
      < 0.05). Apoptosis increased compared with controls (7.21%), after 20-MUM
      treatment with Pio or Rosi, to 10.45% and 12.10%, respectively (P < 0.05). Both
      Pio and Rosi decreased beta-catenin protein levels and increased p-GSK3beta, but
      the LRP5/6, GSK3beta, and TCF7L2 mRNA levels were constant. Upon activation of
      the Wnt pathway by mouse Wnt3a protein, beta-catenin and p-GSK3beta protein
      levels were reversed, accompanied with increased proliferation, but apoptosis
      remained high. CONCLUSIONS: Activation of PPARgamma in osteoblasts accompanied
      Wnt signaling suppression. Activation of Wnt signaling alleviated the PPARgamma
      proliferation decreases but not the apoptosis increases. The thiazolidinedione
      PPARgamma agonists act in part through inhibition of the Wnt signaling pathway,
      showing there is a relationship between PPARgamma and Wnt signaling.

PMID- 25756251
TI  - A short review of applications of liquid chromatography mass spectrometry based
      metabolomics techniques to the analysis of human urine.
AB  - The applications of metabolomics as a methodology for providing better treatment
      and understanding human disease continue to expand rapidly. In this review,
      covering the last two years, the focus is on liquid chromatography-mass
      spectrometry (LC-MS) profiling of metabolites in urine. In LC-MS based
      metabolomics there are still problems with regard to: chromatographic separation,
      peak picking and alignment, metabolite identification, metabolite coverage,
      instrument sensitivity and data interpretation and in the case of urine sample
      normalisation. Progress has been made with regard to all of these issues during
      the period of the review. Of particular interest are the increasing use of
      orthogonal chromatographic methods for optimal metabolite coverage and the
      increasing adoption of receiver operator characteristic (ROC) curves for
      biomarker validation. 

PMID- 25756250
TI  - Demographic and Socioenvironmental Characteristics of Black and White Community
      Dwelling Caregivers and Care Recipients' Behavioral and Psychological Symptoms of
      Dementia.
AB  - The purpose of the current study was to compare the association between caregiver
      background characteristics and care recipients' behavioral and psychological
      symptoms of dementia (BPSD) in Black and White community-dwelling family
      caregivers. Using logistic regression models, caregiver/care recipient dyad data
      from the Aging Demographics and Memory Study were used to describe associations
      between caregiver background characteristics (i.e., demographic and
      socioenvironmental variables) and care recipients' BPSD (i.e., hallucinations,
      delusions, agitation, depression) (N = 755). Results showed that Black caregivers
      were more likely to be female, younger, an adult child, have less education, and
      live in the South (p <= 0.05); they were less likely to be married. Several
      caregiver background characteristics were associated with care recipients'
      depression and agitation, but not with other BPSD. Caregiver background
      characteristics may play a role in the recognition and reporting of BPSD and
      should be considered when working with families of individuals with dementia.

PMID- 25756252
TI  - [When science becomes technology: epistemological and ethical consequences of the
      Adduction].
AB  - Notwithstanding that the sciences are every day closest to technology, the
      Philosophy of Science has not yet well realized the epistemological and ethical
      differences that make different the "Traditional Naturalistic Science" (TNS) and
      the technological, artefactual, intrusive science that I called: "Post-Modern
      Meta-Naturalistic Science" (P-MM-NS). The first type of science has as a primary
      scope the knowledge of nature, using a methodology that departs from the methodic
      doubt, realizes a hypothesis, defines the aim(s), adopts a protocol, interprets
      and discusses the results, inferentially derives the conclusions, according to
      the classical philosophical reasonings of induction, deduction, abduction. In my
      philosophical reasoning, I realized that P-MM-NS follows an absolutely different
      epistemological procedure. The technological science prefigures a scope, produces
      a non-natural technically-modified object, gives for sure the occurrence of the
      effect for which the object has been manufactured. This means that only "in
      retrospect" it will ascertain whether or not the promised effect has occurred,
      considering that any technical artifact could be rejected by that natural
      environment in which it has been, acritically, delivered, without knowing how to
      remedy in case of an unexpected effect. In such a circumstance, the technological
      science has totally failed in its scope and effect, The potential failure of the
      predicted effect will prove that P-MM-NS follows a logical reasoning that is
      substantially and formally "sui generis" with respect to the epistemology and
      ethics of NS. This divergence from the classic reasoning of induction, deduction,
      abduction, has been called by me: "Adduction", because of the following
      considerations: the scientific procedure doesn't depart from the methodic doubt
      and hypothesis, only declares a scope, for which it is produced a technically
      manufactured object, and gives for sure which will be the expected effect, but,
      not knowing how to remedy to negative results in case of a failure. It is, thus,
      clearly visible that the adduction is a type of logical reasoning that is self
      referential and tautogical, being only based on a declaration of intents,
      adducted for justifying the production of a technical artifact, assuring an
      effect without suspecting that it could not respond to the promised scope. 

PMID- 25756253
TI  - Clinical features of potato sensitivity in children with allergic disease.
AB  - BACKGROUND AND OBJECTIVE: Although potato is greatly consumed all over the world,
      adverse reactions to potato are uncommon. Our aim is to describe the clinical
      features of potato sensitivity in allergic children. MATERIALS AND METHODS: Forty
      children with sensitivity to potato were followed up in the Pediatric Immunology
      and Allergy Clinic of our hospital were included in the study. These patients
      were retrospectively evaluated from January 2012 to December 2013. RESULTS: Forty
      children aged between 6 months and 10 years (mean 2.9+/-3.2, median:1.5 years)
      were enrolled of whom 26 were male (65%). Thirty three of these children had
      presented eczema, nine wheezing, seven urticaria and/or angioedema, six rhinitis,
      four subjects had experienced anaphylaxis, and two vomiting or other
      gastrointestinal complaints. In 38 (95%) patients, skin prick tests detected
      sensitivity to other allergens besides potato. The most frequently identified
      sensitivities were to food sensitivities (82.5%). In addition sensitivity to
      house dust mite, cat dander, pollens, A. Alternata and cockroaches in skin prick
      tests were documented in nine, six, five, four and four patients, respectively.
      Latex sensitivity was not detected in any patient. Five (38.5%) out of 13
      patients over the age of three showed sensitivity to pollen. CONCLUSIONS:
      Potatoes sensitivity is mostly seen in children with atopic dermatitis. In
      children with atopic eczema should be asked whether the increase in complaints
      with potatoes. Mostly potato sensitivity is combined with other food allergies.
      Therefore potato should be included in the test in patients with atopic eczema
      and food allergy.

PMID- 25756255
TI  - A new tool in the global fight against the traffic in human organs.
AB  - The Council of Europe (CoE) Convention against Trafficking in Human Organs is a
      significant tool in the global fight against the traffic in human organs for
      transplantation. It is addressed to all states throughout the world, not only to
      CoE member states. The Convention binds states to adopt reciprocally consistent
      and co-ordinated measures to establish organ trafficking as a criminal offence.
      The legal fundamentals and co-ordinated action envisaged in the Convention
      provide practical support in the implementation of principles already sanctioned
      in previous declarations.

PMID- 25756254
TI  - Long term effects of palatal implant method in adult patients with simple snoring
      and obstructive sleep-apnea syndrome.
AB  - OBJECTIVE: To investigate the long term effect and reliability of palatal implant
      surgery, which is a minimally invasive technique, used in simple snoring and
      obstructive sleep-apnea syndrome types based on objective and subjective data.
      MATERIALS AND METHODS: Seventy-eight patients were included prospectively in this
      study. It has been possible to obtain preoperative and postoperative
      polysomnography results in 59 patients. The cases were followed-up for 8 months
      on average. Considering the apnea index and AHI values, the patients were divided
      into 5 groups, namely simple snoring (n=13), mild OSAS (n=21), moderate OSAS
      (n=17), severe OSAS (n=8), and the group on which polysomnography could not be
      performed, the no-polysomnography group (n=19). The cases were evaluated based on
      polysomnography and the Epworth Sleepiness Scale and visual analog scale filled
      by relatives or friends of the patients. RESULTS: The AHI of 46 patients
      diagnosed with OSAS decreased from 14.9 to 10.14 (31% decline) (p=0.279). The AHI
      of 13 patients with simple snoring diagnosis reduced from 3.09 to 2.02 (p=0.033).
      A 40% improvement was observed in VAS of all cases. Implant rejection occurred in
      7 of our cases and 3 patients experienced ecchymosis. CONCLUSIONS: It is
      concluded that palatal implant procedure is a good option for appropriate cases,
      it is equivalent to other methods in terms of treatment efficacy and that is more
      advantageous than other techniques in that it can be applied in office settings
      with low morbidity, is minimally invasive and brings about higher patient
      compliance.

PMID- 25756256
TI  - In defence of non-remunerated blood donation.
AB  - Numerous documents concerning bioethics and human rights recognise that the human
      body and its parts should not be bought or sold or be source of profit.
      Voluntary, non-remunerated donation is recognised by all the major competent
      bodies in the field as a cornerstone for the safe and sustainable supply of blood
      and blood products. In several nations so-called "donors" nonetheless receive
      remuneration or reimbursements that frequently verge on actual payments. In
      addition, there is constant pressure - especially from for-profit organisations-
      to introduce payments for "donors". Against this background it may perhaps be
      useful to reassert the basic principles underlying the non-remunerated donation
      of blood.

PMID- 25756257
TI  - [A case of stable microvascular angina with normal coronary arteries: certainties
      and doubts].
AB  - Myocardial ischemia is caused in most cases by the obstruction of epicardial
      coronary vessels. Several studies, however, have shown that abnormalities in the
      coronary microcirculation can also contribute to myocardial ischemia.
      Microvascular dysfuntion is defined as primary microvascular angina (MVA) to
      distinguish it from other forms of secondary microvascular angina due to such
      diseases as arterial hypertension, left ventricular hypertrophy, myocardial
      disease, metabolic syndrome and collagen diseases. We present the case report of
      a 48-year-old male patient who coronarographically showed coronary slow flow with
      delayed distal vessel opacification in the absence of coronary stenosis. Whilst
      this phenomenon is still not completely understood, strong evidence suggests that
      the primary alteration is caused by a dysfunction of small coronary vessels.

PMID- 25756258
TI  - Electronic cigarette: a threat or an opportunity for public health? State of the
      art and future perspectives.
AB  - The e-cigarette, also known as e-cig, represents an emerging issue of great
      concern for public health. The aim of the present report was to explore the
      scientific literature about the use of electronic cigarette (e-cig), with a
      particular reference to the features of "toxicological safety", "effectiveness in
      overcoming the addiction to smoking the traditional cigarette" and "necessary
      research agenda". The efficacy of e-cig for smoking cessation is uncertain: some
      authors found that it can be a valid support, but long-term cessation rate has
      not be assessed. Other studies evidenced that e-cig is often used not for
      quitting smoking but to avoid smoking ban for traditional cigarettes and, even,
      some researches evidenced that it appears to contribute to nicotine addiction. E
      cig smoking seems to be less dangerous of conventional cigarettes, but its use is
      not risk-free. Besides, cases of accidental or intentional poisoning with liquid
      solutions of e-cig have been reported. Also, the smoke of e-cig decreases indoor
      air quality, releasing particulate matter and other toxics that can persist on
      surfaces for days and generating passive exposure. These phenomena are similar to
      environmental tobacco smoke produced by conventional smoking, that is the sum of
      second- and third-hand smoke. We propose to call them "environmental electronic
      smoke", "electronic-second- hand smoke" and "electronic-third-hand smoke",
      respectively. Uncertainties relating to e-cig features determined the sequence,
      in the short term, of warnings and regulations approved and then replaced. In
      conclusion, although in recent years many researches were performed, evidences is
      limited and there is a need to study in deep all these issues.

PMID- 25756259
TI  - [On the moral dutifulness of using vaccinations].
AB  - People had contradictory opinions on using vaccinations over time: an initial
      opposition, later large favour and then doubts and perplexities. In recent times,
      some movements, blogs and associations stigmatize the use of vaccinations and
      they are increasingly asking to remove mandatory vaccinations in countries where
      they are active. The impact of the antivaccination campaigns should not be
      underestimated, considering that, for example, in Italy, due to these campaigns,
      adhesions to vaccinations are decreasing by 1% per year, and in reference to
      rubella and measles, adhesions decreased by 25% in some regions of the country.
      Overcoming the choice between mandatory and recommended vaccinations, the paper
      deals with the topic of using preventive immunization starting from the concept
      of "moral dutifulness".

PMID- 25756260
TI  - A rare case of gastrointestinal bleeding due to celiax axis stenosis with
      subsequent hypertrophied pancreaticoduodenal arcades.

PMID- 25756261
TI  - [The longsurvivors for non-small cell lung cancer: remarks on the present and in
      perspective].
AB  - The Authors fully share cricitisms voiced in international literature to NSCLC
      longsurvivors, in particular those remarkes related to advanced disease patients
      following various anti-tumor treatments ( mostly multimodal). To this point, even
      the NCCN version 3.2014 guidelines prove inadequate as they mostly focus on
      longsurvivors post-NSCLC early stage surgical resection. Although AIOM Working
      Group's recommendations for follow-up seem to be more adequate, still they lack
      depth with respect to advanced-stage bronchogenic carcinoma. The Authors quote a
      number of case report related to advanced disease longsurvivors, and draws his
      attention on the peculiar role of pneumologists in the follow-up for such
      patients: in particular, as regards respiratory pathologies prior or subsequent
      to different anti-tumor treatments (i.e., BPCO, interstitial lung diseases,
      pulmonary thromboembolism, etc.).

PMID- 25756262
TI  - [Prolonged exposure to urban pollutants and arterial blood pressure: a whole
      evaluation of our researches].
AB  - AIM: A significant relationship between exposure to cadmium and PAHs from urban
      air pollution and blood pressure has already been found. The aim of the study is
      to evaluate if other urban pollutants maintain a similar relationship in outdoor
      workers. MATERIALS AND METHODS: 349 subjects of both sexes were enrolled in the
      study; we evaluated values of environmental and biological monitoring of
      respirable dust, arsenic, lead, benzene, toluene, xylene and we measured blood
      pressure (BP) in upright and in supine position; to analyze data we used multiple
      linear regression. Also we valued our results in the light of those we have
      obtained in previous research. RESULTS: Multiple linear regression showed no
      significant results that demonstrate a relationship between BP and these
      pollutants. CONCLUSIONS: The results of our study lead to assume that exposure to
      urban pollutants studied has not connection with blood pressure, and to retain
      valid the relationship previously observed for cadmium and PAHs, which seem to be
      the only pollutants that can affect blood pressure.

PMID- 25756263
TI  - Component analysis of 251 cases of urinary calculi in Uigurs and Han in
      Xingjiang.
AB  - OBJECTIVE: To explore the relationship between urolithiasis and related factors
      by chemical analysis of urolithic components in the urine and serum of Uigurs and
      Han in Xingjiang. MATERIALS AND METHODS: A series of 251 inpatients' urinary
      calculi (Uigurs: 148; Han: 103) were qualitatively chemically analyzed. Their
      serum and urine biochemistry was determined using an automatic biochemical
      machine. RESULTS: There are significant differences between the Uigurs and the
      Han (p<0.05) in the ratio of reoccurrence of urinary calculi, age and region;
      calcium oxalate has the highest concentration (Uigurs: 75.68%; Han: 60.78%).
      There are significant differences (p<0.05) in serum phosphate (HPO42-) levels,
      urine specific gravity and uric acid, with the Uigurs having higher levels than
      that of the Han. CONCLUSIONS: 1. Differences in distributions of urolithic
      components between Uigurs and Han in Xingjiang are not significant; 2. The ratios
      of reoccurrence and ages are significantly different. The children and youth of
      Uigurs have higher rates of occurrence than the Han. There are notable
      differences in serum HPO42-, urine specific gravity, and uric acid between Uigurs
      and the Han. The ratio of Uigurs is notably higher than that of the Han. All
      these differences may result from differences in race, dietary habits, and
      physical activity.

PMID- 25756264
TI  - [Surgical treatment of osteochondromas: indication in "Strategic Exostosis"].
AB  - OBJECTIVE: The osteochondromas represents is the most frequent benign lesion
      interesting the bone tissue. This lesion, often asymptomatic, can arise through
      mechanical, irritative or painful syndromes: "strategic exostosis". MATERIALS AND
      METHODS: In our present study we retrospectively evaluated 65 Caucasian patients,
      which have been treated surgically for symptomatic solitary exostosis from March
      2004 to Jan 2011. The most frequent symptom referred by patient has been
      represented by pain. The others complains were related to nervous compression,
      esthetic injury and a reduction of range of motion. By using the VAS score we
      evaluated the post-operative bone pain at 3, 12 and 24 months. At the end of
      follow up we evaluated by a validated questionnaire the grade of patient
      satisfaction. RESULTS: No major surgical complication were found. The rate of
      disease recidivism was null. Only a small group of patient referred a persisting
      pain in the lesion area during the two years follow up. In this subgroup the rate
      of satisfaction was obviously reduced. CONCLUSIONS: In our opinion the surgical
      treatment of strategic exostosis, is safe and it should be recommended, since it
      allows to eliminate the noise with a low incidence of complications. The large
      majority of out patients were satisfied of the clinical improvement they
      experienced.

PMID- 25756265
TI  - [Changes in tobacco addiction and spirometric variations in workers exposed to
      chemical risk in biochemical research laboratories of a large Italian University-
      a retrospective cohort study].
AB  - OBJECTIVE: To describe smoking cessation in a group of workers exposed to
      chemical risk and factors associated; to assess the changes of respiratory
      function over the years also in relation to risks to which they were exposed.
      MATERIALS AND METHODS: We studied employees/students occupationally exposed to
      chemical risk from whom we also had information about smoking status and who had
      done a spirometry in all periodic visits and who had at least two periodic
      medical examinations during the follow-up. RESULTS: Variables significantly
      associated to the smoking cessation are gender and exposure to biological risk.
      The changes in Forced Vital Capacity between the last and the first visit were
      associated to a significant negative correlation, from multivariate analysis, to
      age and to exposure to the display screen equipment. The Tiffeneau index was
      significantly positively associated with exposure to display screen equipment and
      to manual handling of loads; the Forced Expiratory Flow 25-75% was significantly
      associated with physical risk. CONCLUSIONS: A greater awareness on the
      consequences of smoking is recommended in subjects exposed to chemical risk,
      especially in women, in addition to a serial monitoring of lung function in order
      to carry out an early intervention in the first phase of airflow limitation.

PMID- 25756266
TI  - Interferon-gamma-inducible chemokines in systemic lupus erythematosus.
AB  - Some studies reported that chemokine interferon-gamma-inducible protein 10 (IP
      10) and its receptor chemokine (C-X-C motif) receptor (CXCR) 3, which is
      exhibited by T cells, are expressed in several types of cutaneous damages
      associated with Systemic Lupus Erythematosus (SLE), and that the CXCR3-activating
      chemokines are produced locally, suggesting their significant role in the
      recruitment of T cells in these inflammatory lesions. The involvement of IP-10
      and CXCR3 has been shown also in several other types of tissue damages associated
      with SLE, such as glomerulonephritis or central nervous system lupus. Urinary IP
      10 is a sensitive and non-invasive diagnostic tool for monitoring lupus nephritis
      patients, and the response to treatments. Serum levels of IP-10 are increased in
      SLE patients, showing a strong correlation with disease activity. Levels of IP-10
      are also increased in the cerebrospinal fluid samples from neuropsychiatric SLE
      patients. These data provide increasing evidence that IP-10 may participate in
      the pathogenesis of a variety of the manifestations of SLE, even if the exact
      role of IP-10 in the pathogenesis of SLE remains to be clarified.

PMID- 25756267
TI  - [Parricide, abuse and emotional processes: a review starting from some
      paradigmatic cases].
AB  - The authors of this study tackle the complex subject of parricide, which is a
      rare and often brutal form of homicide. Parricide has a high emotional impact on
      public opinion and on our collective imagination, especially in light of the fact
      that the perpetrators are often minors.. Three striking cases of parricide, taken
      from various documented sources and judicial files from the "N. Fornelli"
      Juvenile Penal Institute (Bari, Italy), are presented here. A review of the
      literature on the topic has revealed differences between parricides committed by
      adults and those committed by minors. In the end, the complex issues underlying
      such an unusual crime are connected to abuses and maltreatment that minor
      perpetrators of parricide have suffered, especially the emotional processes that
      are activated.

PMID- 25756268
TI  - The CXCR3 chemokines in inflammatory myopathies.
AB  - The alpha-chemokines (C-X-C motif) ligand 9 (CXCL9) and interferon gamma-induced
      protein 10 (IP-10) are expressed in idiopathic inflammatory myopathies muscle.
      Abundant expression of IP-10 was observed on macrophages and T cells surrounding
      and invading non-necrotic muscle fibers in polymyositis and sporadic inclusion
      body myositis and in T cells in perimysial infiltrates of dermatomyositis. IP-10
      was also localized to blood vessel endothelial cells in all inflammatory and
      normal muscle tissues. Serum IP-10 is high in patients with inflammatory
      myopathies. Human skeletal muscle cells might actively self-promote muscular
      inflammation by eliciting IP-10 secretion, under the influence of cytokines
      [Interferon (IFN-gamma), Tumor Necrosis Factor (TNF-alpha)], which can amplify T
      helper (Th)1 cell tissue infiltration in vivo. It has been shown that drugs able
      to block the IP-10/chemokine (C-X-C motif) receptor 3 (CXCR3) axis can suppress
      inflammation in muscle.

PMID- 25756269
TI  - Cytokines and chemokines in multiple sclerosis.
AB  - Chemokine (C-X-C motif) receptor 3 (CXCR3) and its ligands (MIG, IP-10) play an
      important role in multiple sclerosis (MS). The CXCR3 receptor is expressed on the
      majority of T cells in the cerebrospinal fluid (CSF) of patients with MS,
      suggesting that the CXCR3 receptor may mediate the trafficking of T cells into
      the central nervous system. IP-10, and MIG were found to be elevated in the CSF
      of patients with MS during relapse. These chemokines were also detected in
      actively demyelinating lesions, and upregulation of CXCR3 expression on
      peripheral blood CD4+ lymphocytes was associated with MS relapses.Treatment with
      Interferon (IFN)-beta-1a or IFN-beta-1b was associated with increased IP-10.
      Natalizumab that exerts impressive therapeutic effects in patients with MS
      induces a marked decline of Th1 chemokines (MIG, IP-10, I-TAC) in CSF. 

PMID- 25756270
TI  - [Troponin I and B-type Natriuretic Peptide (BNP) as biomarkers for the prediction
      of cardiotoxicity in patients with breast cancer treated with adjuvant
      anthracyclines and trastuzumab].
AB  - Adjuvant trastuzumab with chemotherapy is the treatment of choice for patients
      with human epidermal growth factor receptor positive (HER2+) breast cancer and
      improves the outcome of patients with early breast cancer. However, it is
      potentially cardiotoxic and there are no validated methods of early detection of
      cardiotoxicity from trastuzumab following anthracycline-based chemotherapy.
      Currently, changes in left ventricular ejection fraction (LVEF) are assessed but
      this approach has limited sensitivity and specificity. Early identification of
      patients at risk for cardiotoxic effects is a primary goal for both cardiologists
      and oncologists. Plasma markers such as b-type natriuretic peptide (BNP - an
      index of elevated filling pressure) and troponin I (TnI - an index of
      cardiomyocyte damage) may be used to identify the risk of developing cardiac
      dysfunction during treatment. In this review, we discuss if TnI and/or BNP could
      be used to help the prevention or treatment of cardiac dysfunction at the
      earliest possible time.

PMID- 25756271
TI  - [Stress and work-related injuries].
AB  - OBJECTIVE: The aim of this study was to evaluate in scientific literature the
      more frequent work injuries among the occupational categories examined
      (construction workers, healthcare workers, night workers and shift work, drivers)
      and to identify occupational stressors that increase the risk of injury.
      MATERIALS AND METHODS: The research was conducted through review of the
      scientific literature between 1990 and 2014. Two hundred articles were found of
      which 42 selected in the following categories: construction workers, healthcare
      workers, shift workers, lorry drivers. RESULTS: The movement of machinery and
      working at height are due to injury for building sector and they were positively
      correlated with physical (r = 0,206) and mental (r = 0,254) stress. In health
      workers the injuries are more frequently bruises and sprains (50%). Studies
      showed a higher rate of injury in a group of shift workers compared to a control
      group on a rota basis (p <0.0001). Road accidents for drivers represent the most
      frequent cause of injury of which 13% comes from falling asleep, while 31% from
      distractions (OR = 3.16; CI = 1:22 to 8:24). CONCLUSIONS: Nurses have frequent
      injuries due to bruises, lumbago, punctures with needles and surgical wounds.
      Construction workers often suffer serious injury derived from falls at height,
      handling machinery. For workers on a rota basis, injuries are often related to
      lack of sleep. Road accidents in drivers are the most common injuries. A
      synergistic action finalized to promote health and safety organization, to ensure
      a work environment more secure, is advisable.

PMID- 25756272
TI  - Sarcoidosis and Th1 chemokines.
AB  - Many studies have shown high levels of the chemokine Interferon-gamma-inducible
      protein 10 (IP-10) and its chemokine (C-X-C motif) receptor (CXCR) 3, expressed
      on Type-1 helper (Th1) lymphocytes, in bronchoalveolar lavage (BAL) and biopsy
      samples of patients with sarcoidosis. The levels of IP-10 and the other CXCR3
      ligands, Monokine induced by IFN-gamma (MIG) and Interferon-inducible T-cell
      alpha chemoattractant (I-TAC), in bronchoalveolar lavage fluid (BALF) were
      correlated with the numbers of both total and CD4(+) lymphocytes. Alveolar
      macrophages were stained positive for all CXCR3 ligands and produced increased
      amounts of these chemokines. This positive staining was also observed in the
      epithelioid and giant cells in the sarcoid lungs. These findings suggest that IP
      10, MIG and I-TAC play important roles in the accumulation of Th1 lymphocytes in
      sarcoid lungs. Furthermore, it has been demonstrated that circulating IP-10
      levels correlated with measures of disease severity in sarcoidosis, and that its
      serial measurements corresponded to the clinical course of the disease,
      suggesting that IP-10 is a potentially useful biomarker of sarcoidosis and its
      severity.

PMID- 25756273
TI  - The potential protective role of caveolin-1 in intestinal inflammation in TNBS
      induced murine colitis.
AB  - BACKGROUND: Caveolin-1 (Cav-1) is a multifunctional scaffolding protein serving
      as a platform for the cell's signal-transduction and playing an important role in
      inflammation. However, its role in inflammatory bowel disease is not clear. A
      recent study showed that Cav-1 is increased and mediates angiogenesis in dextran
      sodium sulphate-induced colitis, which are contradictory to our pilot findings in
      2,4,6-trinitrobenzene sulphonic acid (TNBS)-induced colitis. In the present
      study, we further clarified the role of Cav-1 in TNBS-induced colitis. METHODS:
      In BALB/c mice, acute colitis was induced by intra-rectal administration of one
      dose TNBS, while chronic colitis was induced by administration of TNBS once a
      week for 7 weeks. To assess the effects of complete loss of Cav-1, Cav-1 knockout
      (Cav-1-/-) and control wild-type C57 mice received one TNBS administration. Body
      weight and clinical scores were monitored. Colon Cav-1 and pro-inflammatory
      cytokine levels were quantified through ELISAs. Inflammation was evaluated
      through histological analysis. RESULTS: Colon Cav-1 levels were significantly
      decreased in TNBS-induced colitis mice when compared to normal mice and also
      inversely correlated with colon inflammation scores and proinflammatory cytokine
      levels (IL-17, IFN-gamma and TNF) significantly. Furthermore, after
      administration of TNBS, Cav-1-/- mice showed significantly increased clinical and
      colon inflammatory scores and body weight loss when compared with control mice.
      CONCLUSIONS AND SIGNIFICANCE: Cav-1 may play a protective role in the development
      of TNBS-induced colitis. Our findings raise an important issue in the evaluation
      of specific molecules in animal models that different models may exhibit opposite
      results because of the different mechanisms involved.

PMID- 25756274
TI  - Comparison of efficacy and tolerance of short-duration open-ended ureteral
      catheter drainage and tamsulosin administration to indwelling double J stents
      following ureteroscopic removal of stones.
AB  - OBJECTIVES: To evaluate the efficacy of short-duration, open-ended ureteral
      catheter drainage as a replacement to indwelling stent, and to study the effect
      of tamsulosin on stent-induced pain and storage symptoms following uncomplicated
      ureteroscopic removal of stones. DESIGN: Prospective randomised study. SETTING:
      School of Medical Sciences and Research, Sharda University, Greater Noida, India.
      PATIENTS: Patients who underwent ureteroscopic removal of stones for lower
      ureteral stones between November 2011 and January 2014 were randomly assigned
      into three groups. Patients in group 1 (n=33) were stented with 5-French double J
      stent for 2 weeks. Patients in group 2 (n=35) were administered tablet tamsulosin
      0.4 mg once daily for 2 weeks in addition to stenting, and those in group 3
      (n=31) underwent 5-French open-ended ureteral catheter drainage for 48 hours.
      MAIN OUTCOME MEASURES: All patients were evaluated for flank pain using visual
      analogue scale scores at days 1, 2, 7, and 14, and for storage (irritative)
      bladder symptoms using International Prostate Symptom Score on days 7 and 14, and
      for quality-of-life score (using International Prostate Symptom Score) on day 14.
      RESULTS: Of the 99 patients, visual analogue scale scores were significantly
      lower for groups 2 and 3 (P<0.0001). The International Prostate Symptom Scores
      for all parameters were lower in patients from groups 2 and 3 compared with group
      1 both on days 7 and 14 (P<0.0001). Analgesic requirements were similar in all
      three groups. CONCLUSION: Open-ended ureteral catheter drainage is equally
      effective and better tolerated than routine stenting following uncomplicated
      ureteroscopic removal of stones. Tamsulosin reduces storage symptoms and improves
      quality of life after ureteral stenting.

PMID- 25756275
TI  - Prospective study on the effects of orthotic treatment for medial knee
      osteoarthritis in Chinese patients: clinical outcome and gait analysis.
AB  - OBJECTIVE: To evaluate the effectiveness of various orthotic treatments for
      patients with isolated medial compartment osteoarthritis. DESIGN: Prospective
      cohort study with sequential interventions. SETTING: University-affiliated
      hospital, Hong Kong. PATIENTS: From December 2010 to November 2011, 10 patients
      with medial knee osteoarthritis were referred by orthopaedic surgeons for
      orthotic treatment. All patients were sequentially treated with flat insole,
      lateral-wedged insole, lateral-wedged insole with subtalar strap, lateral-wedged
      insole with arch support, valgus knee brace, and valgus knee brace with lateral
      wedged insole with arch support for 4 weeks with no treatment break. Three
      dimensional gait analysis and questionnaires were completed after each orthotic
      treatment. MAIN OUTCOME MEASURES: The Western Ontario and McMaster Universities
      Arthritis Index (WOMAC), visual analogue scale scores, and peak and mean knee
      adduction moments. RESULTS: Compared with pretreatment, the lateral-wedged
      insole, lateral-wedged insole with arch support, and valgus knee brace groups
      demonstrated significant reductions in WOMAC pain score (19.1%, P=0.04; 18.2%,
      P=0.04; and 20.4%, P=0.02, respectively). The lateral-wedged insole with arch
      support group showed the greatest reduction in visual analogue scale score
      compared with pretreatment at 24.1% (P=0.004). Addition of a subtalar strap to
      lateral-wedged insoles (lateral-wedged insole with subtalar strap) did not
      produce significant benefit when compared with the lateral-wedged insole alone.
      The valgus knee brace with lateral-wedged insole with arch support group
      demonstrated an additive effect with a statistically significant reduction in
      WOMAC total score (-26.7%, P=0.01). Compliance with treatment for the isolated
      insole groups were all over 90%, but compliance for the valgus knee brace
      associated groups was only around 50%. Gait analysis indicated statistically
      significant reductions in peak and mean knee adduction moments in all orthotic
      groups when compared with a flat insole. CONCLUSIONS: These results support the
      use of orthotic treatment for early medial compartment knee osteoarthritis.

PMID- 25756276
TI  - Impact of nuchal cord on fetal outcomes, mode of delivery, and management: a
      questionnaire survey of pregnant women.
AB  - OBJECTIVES: To explore pregnant women's views on the impact of nuchal cord on
      fetal outcomes, mode of delivery, and management. DESIGN: Questionnaire survey.
      SETTING: Antenatal clinic of two regional hospitals in Hong Kong. PARTICIPANTS: A
      questionnaire survey of all pregnant women at their first visit to the antenatal
      clinic of United Christian Hospital and Tseung Kwan O Hospital in Hong Kong was
      conducted between August and October 2012. RESULTS: Most participants (71.8%)
      were worried about nuchal cord, and 78.3% and 87.7% of them thought that nuchal
      cord could cause intrauterine death and fetal death during labour, respectively.
      Approximately 87.5% of participants thought that nuchal cord would reduce the
      chance of successful vaginal delivery and 56.4% thought that it would increase
      the chance of assisted vaginal delivery. Most (94.1%) participants thought that
      it was necessary to have an ultrasound scan at term to detect nuchal cord. In
      addition, 68.8% thought that it was necessary to deliver the fetus early and
      72.8% thought that caesarean section must be performed in the presence of nuchal
      cord. Participants born in Mainland China were significantly more worried about
      the presence of nuchal cord than those born in Hong Kong. However, there was no
      difference between participants with different levels of education. CONCLUSION:
      Most participants were worried about the presence of nuchal cord. Many thought
      that nuchal cord would lead to adverse fetal outcomes, affect the mode of
      delivery, and require special management. These misconceptions should be
      addressed and proper education of women is needed.

PMID- 25756278
TI  - Vitamin B12 deficiency in the elderly: is it worth screening?
AB  - Vitamin B12 deficiency is common among the elderly. Elderly people are
      particularly at risk of vitamin B12 deficiency because of the high prevalence of
      atrophic gastritis-associated food-cobalamin (vitamin B12) malabsorption, and the
      increasing prevalence of pernicious anaemia with advancing age. The deficiency
      most often goes unrecognised because the clinical manifestations are highly
      variable, often subtle and non-specific, but if left undiagnosed the consequences
      can be serious. Diagnosis of vitamin B12 deficiency, however, is not
      straightforward as laboratory tests have certain limitations. Setting a cut-off
      level to define serum vitamin B12 deficiency is difficult; though homocysteine
      and methylmalonic acid are more sensitive for vitamin B12 deficiency, it may give
      false result in some conditions and the reference intervals are not standardised.
      At present, there is no consensus or guideline for diagnosis of this deficiency.
      It is most often based on the clinical symptoms together with laboratory
      assessment (low serum vitamin B12 level and elevated serum homocysteine or
      methylmalonic acid level) and the response to treatment to make definitive
      diagnosis. Treatment and replacement with oral vitamin B12 can be as effective as
      parenteral administration even in patients with pernicious anaemia. The suggested
      oral vitamin B12 dose is 1 mg daily for a month, and then maintenance dose of 125
      to 250 ug for patients with dietary insufficiency and 1 mg daily for those with
      pernicious anaemia. Vitamin B12 replacement is safe and without side-effects, but
      prompt treatment is required to reverse the damage before it becomes extensive or
      irreversible. At present, there is no recommendation for mass screening for
      vitamin B12 in the elderly. Nevertheless, the higher prevalence with age,
      increasing risk of vitamin B12 deficiency in the elderly, symptoms being
      difficult to recognise, and availability of safe treatment options make screening
      a favourable option. However, the unavailability of reliable diagnostic tool or
      gold standard test makes screening difficult to carry out. 

PMID- 25756277
TI  - Surveillance of emerging drugs of abuse in Hong Kong: validation of an analytical
      tool.
AB  - OBJECTIVE: To validate a locally developed chromatography-based method to monitor
      emerging drugs of abuse whilst performing regular drug testing in abusers.
      DESIGN: Cross-sectional study. SETTING: Eleven regional hospitals, seven social
      service units, and a tertiary level clinical toxicology laboratory in Hong Kong.
      PARTICIPANTS: A total of 972 drug abusers and high-risk individuals were
      recruited from acute, rehabilitation, and high-risk settings between 1 November
      2011 and 31 July 2013. A subset of the participants was of South Asian ethnicity.
      In total, 2000 urine or hair specimens were collected. MAIN OUTCOME MEASURES:
      Proof of concept that surveillance of emerging drugs of abuse can be performed
      whilst conducting routine drug of abuse testing in patients. RESULTS: The method
      was successfully applied to 2000 samples with three emerging drugs of abuse
      detected in five samples: PMMA (paramethoxymethamphetamine), TFMPP [1-(3
      trifluoromethylphenyl)piperazine], and methcathinone. The method also detected
      conventional drugs of abuse, with codeine, methadone, heroin, methamphetamine,
      and ketamine being the most frequently detected drugs. Other findings included
      the observation that South Asians had significantly higher rates of using opiates
      such as heroin, methadone, and codeine; and that ketamine and cocaine had
      significantly higher detection rates in acute subjects compared with the
      rehabilitation population. CONCLUSIONS: This locally developed analytical method
      is a valid tool for simultaneous surveillance of emerging drugs of abuse and
      routine drug monitoring of patients at minimal additional cost and effort.
      Continued, proactive surveillance and early identification of emerging drugs will
      facilitate prompt clinical, social, and legislative management.

PMID- 25756280
TI  - Distinctive features of NREM parasomnia behaviors in parkinson's disease and
      multiple system atrophy.
AB  - OBJECTIVE: To characterize parasomnia behaviors on arousal from NREM sleep in
      Parkinson's Disease (PD) and Multiple System Atrophy (MSA). METHODS: From 30
      patients with PD, Dementia with Lewy Bodies/Dementia associated with PD, or MSA
      undergoing nocturnal video-polysomnography for presumed dream enactment behavior,
      we were able to select 2 PD and 2 MSA patients featuring NREM Parasomnia Behviors
      (NPBs). We identified episodes during which the subjects seemed to enact dreams
      or presumed dream-like mentation (NPB arousals) versus episodes with
      physiological movements (no-NPB arousals). A time-frequency analysis (Morlet
      Wavelet Transform) of the scalp EEG signals around each NPB and no- NPB arousal
      onset was performed, and the amplitudes of the spectral frequencies were compared
      between NPB and no-NPB arousals. RESULTS: 19 NPBs were identified, 12 of which
      consisting of 'elementary' NPBs while 7 resembling confusional arousals. With
      quantitative EEG analysis, we found an amplitude reduction in the 5-6 Hz band 40
      seconds before NPBs arousal as compared to no-NPB arousals at F4 and C4
      derivations (p<0.01). CONCLUSIONS: Many PD and MSA patients feature various NREM
      sleep-related behaviors, with clinical and electrophysiological differences and
      similarities with arousal parasomnias in the general population. SIGNIFICANCE:
      This study help bring to attention an overlooked phenomenon in neurodegenerative
      diseases.

PMID- 25756279
TI  - Simultaneous and dose dependent melanoma cytotoxic and immune stimulatory
      activity of betulin.
AB  - Conventional cytostatic cancer treatments rarely result in the complete
      eradication of tumor cells. Therefore, new therapeutic strategies focus on
      antagonizing the immunosuppressive activity of established tumors. In particular,
      recent studies of antigen-loaded dendritic cells (DCs) eliciting a specific
      antitumor immune response has raised the hopes of achieving the complete
      elimination of tumor tissue. Genistein, fingolimod and betulin have already been
      described as active compounds in different types of cancer. Herein, we applied an
      integrated screening approach to characterize both their cytostatic and their
      immune-modulating properties side-by-side. As will be described in detail, our
      data confirmed that all three compounds exerted proapoptotic and
      antiproliferative activity in different B16 melanoma cell lines to a given
      extent, as revealed by an MTT assay, CFSE and DAPI staining. However, while
      genistein and fingolimod also affected the survival of primary bone marrow (BM)
      derived DCs of C57BL/6 mice, betulin exhibited a lower cytotoxicity for BMDCs in
      comparison to the melanoma cells. Moreover, we could show for the first time,
      that only betulin caused a simultaneous, highly specific immune-stimulating
      activity, as measured by the IL-12p70 release of Toll-like receptor 4-stimulated
      BMDCs by ELISA, which was due to increased IL-12p35 mRNA expression.
      Interestingly, the activation of DCs resulted in enhanced T lymphocyte
      stimulation, indicated by increased IL-2 and IFN-gamma production of cytotoxic T
      cells in spleen cell co-culture assays which led to a decreased viability of B16
      cells in an antigen specific model system. This may overcome the
      immunosuppressive environment of a tumor and destroy tumor cells more effectively
      in vivo if the immune response is specific targeted against the tumor tissue by
      antigen-loaded dendritic cells. In summary, cytostatic agents, such as betulin,
      that simultaneously exhibit immune stimulatory activity may serve as lead
      compounds and hold great promise as a novel approach for an integrated cancer
      therapy. 

PMID- 25756281
TI  - Mortality due to malignant and non-malignant diseases in Korean professional
      emergency responders.
AB  - OBJECTIVE: This study was conducted to estimate the cause-specific mortality in
      male emergency responders (ER), compare with that of Korean men. Mortality was
      also compared between more experienced firefighters (i.e., firefighters employed
      >= 20 years and firefighters employed >= 10 to < 20 years) and less experienced
      firefighters and non-firefighters (i.e., firefighters employed < 10 years and non
      firefighters) to investigate associations between mortality and exposure to
      occupational hazards. METHODS: The cohort was comprised of 33,442 males who were
      employed as ERs between 1980 and 2007 and not deceased as of 1991. Work history
      was merged with the death registry from the National Statistical Office of Korea
      to follow-up on mortality between 1992 and 2007. Standardized mortality ratios
      (SMR) for ERs were calculated in reference to the Korean male population.
      Adjusted relative risks (ARRs) of mortalities for firefighters employed >= 20
      years and >= 10 years to < 20 years were calculated in reference to non
      firefighters and firefighters employed < 10 years. RESULTS: Overall (SMR = 0.43,
      95%CI = 0.39-0.47) and some kinds of cause-specific mortalities were
      significantly lower among ERs compared with the Korean male population. No
      significant increase in mortality was observed across the major ICD-10
      classifications among ERs. Mortality due to exposure to smoke, fire, and flames
      (SMR = 3.11, 95% CI = 1.87-4.85), however, was significantly increased among ERs.
      All-cause mortality (ARR = 1.46, 95% CI=1.13-1.89), overall cancer mortality (ARR
      = 1.54, 95% CI = 1.02-2.31) and mortality of external injury, poisoning and
      external causes (ARR = 3.13, 95% CI = 1.80-5.46) were significantly increased
      among firefighters employed >= 20 years compared to those of non-firefighters and
      firefighters employed < 10 years. CONCLUSIONS: An increase in mortality due to
      all cancer and external injury, poisoning, and external causes in firefighters
      employed >= 20 years compared with non-firefighters and firefighters employed <
      10 years suggests occupational exposure.

PMID- 25756282
TI  - Actin cytoskeleton regulation of epithelial mesenchymal transition in metastatic
      cancer cells.
AB  - Epithelial-mesenchymal transition (EMT) is associated with loss of the cell-cell
      adhesion molecule E-cadherin and disruption of cell-cell junctions as well as
      with acquisition of migratory properties including reorganization of the actin
      cytoskeleton and activation of the RhoA GTPase. Here we show that
      depolymerization of the actin cytoskeleton of various metastatic cancer cell
      lines with Cytochalasin D (Cyt D) reduces cell size and F-actin levels and
      induces E-cadherin expression at both the protein and mRNA level. Induction of E
      cadherin was dose dependent and paralleled loss of the mesenchymal markers N
      cadherin and vimentin. E-cadherin levels increased 2 hours after addition of Cyt
      D in cells showing an E-cadherin mRNA response but only after 10-12 hours in HT
      1080 fibrosarcoma and MDA-MB-231 cells in which E-cadherin mRNA level were only
      minimally affected by Cyt D. Cyt D treatment induced the nuclear-cytoplasmic
      translocation of EMT-associated SNAI 1 and SMAD1/2/3 transcription factors. In
      non-metastatic MCF-7 breast cancer cells, that express E-cadherin and represent a
      cancer cell model for EMT, actin depolymerization with Cyt D induced elevated E
      cadherin while actin stabilization with Jasplakinolide reduced E-cadherin levels.
      Elevated E-cadherin levels due to Cyt D were associated with reduced activation
      of Rho A. Expression of dominant-negative Rho A mutant increased and dominant
      active Rho A mutant decreased E-cadherin levels and also prevented Cyt D
      induction of E-cadherin. Reduced Rho A activation downstream of actin remodelling
      therefore induces E-cadherin and reverses EMT in cancer cells. Cyt D treatment
      inhibited migration and, at higher concentrations, induced cytotoxicity of both
      HT-1080 fibrosarcoma cells and normal Hs27 fibroblasts, but only induced
      mesenchymal-epithelial transition in HT-1080 cancer cells. Our studies suggest
      that actin remodelling is an upstream regulator of EMT in metastatic cancer
      cells. 

PMID- 25756284
TI  - The Effect of Predeparture Training Loads on Posttour Physical Capacities in High
      Performance Junior Tennis Players.
AB  - PURPOSE: Difficulties in preserving physical capacities while on tennis tours
      necessitate targeted training prescription. This study analyzed training and
      match loads performed before and on tour for their relationship with posttour
      physical-capacity changes. A secondary aim was to determine whether the presence
      of a strength and conditioning (S&C) coach affected the type and volume of on
      tour training load. METHODS: The training and match loads of 30 high-performance
      junior tennis players were recorded over 8 wk: 4 wk before and 4 wk during an
      international tour. Fitness tests were conducted pretour and posttour, including
      double and single-leg (dominant and nondominant) countermovement jump, speed (5,
      10, and 20 m), modified 5-0-5 agility, 10 * 20-m repeated-sprint ability, and
      multistage fitness tests. Tour training and match loads were categorized
      according to whether S&C support was present or absent. RESULTS: Total and tennis
      training loads were significantly greater on tour than pretour (P <= .05, d >
      0.8). Increases in on-tour, on-court training loads were moderately correlated
      with decrements in speed and aerobic power (r = .31-.52). Finally, S&C presence
      on tour significantly increased total, on-court, and off-court training load
      completed (P <= .05, d > 0.8). CONCLUSIONS: Training loads should be carefully
      prescribed to ensure that sufficient total and tennis loads are completed
      pretour. Specifically, speed and aerobic capacities may regress with increased
      training on tour. Finally, a practical observation was that on-tour S&C support
      resulted in increased S&C training load (around match loads), potentially
      countering the observed regression of physical capacities. Such a finding has the
      capacity to alter current physical-preparation structures in high-performance
      tennis environments with finite resources.

PMID- 25756283
TI  - Non-carrier nanoparticles adjuvant modular protein vaccine in a particle
      dependent manner.
AB  - Nanoparticles are increasingly used to adjuvant vaccine formulations due to their
      biocompatibility, ease of manufacture and the opportunity to tailor their size,
      shape, and physicochemical properties. The efficacy of similarly-sized silica (Si
      OH), poly (D,L-lactic-co-glycolic acid) (PLGA) and poly caprolactone (PCL)
      nanoparticles (nps) to adjuvant recombinant capsomere presenting antigenic M2e
      modular peptide from Influenza A virus (CapM2e) was investigated in vivo.
      Formulation of CapM2e with Si-OH or PLGA nps significantly boosted the
      immunogenicity of modular capsomeres, even though CapM2e was not actively
      attached to the nanoparticles prior to injection (i.e., formulation was by simple
      mixing). In contrast, PCL nps showed no significant adjuvant effect using this
      simple-mixing approach. The immune response induced by CapM2e alone or formulated
      with nps was antibody-biased with very high antigen-specific antibody titer and
      less than 20 cells per million splenocytes secreting interferon gamma.
      Modification of silica nanoparticle surface properties through amine
      functionalization and pegylation did not lead to significant changes in immune
      response. This study confirms that simple mixing-based formulation can lead to
      effective adjuvanting of antigenic protein, though with antibody titer dependent
      on nanoparticle physicochemical properties. 

PMID- 25756285
TI  - HIV treatment-as-prevention research: taking the right road at the crossroads.
AB  - Reflecting on a Policy Forum article by Till Barnighausen and colleagues, the
      HPTN 071 (PopART) Study Team consider ethical and study power concerns and the
      importance of the trial's future findings. 

PMID- 25756286
TI  - Changes in retinal function and morphology are early clinical signs of disease in
      cattle with bovine spongiform encephalopathy.
AB  - Bovine spongiform encephalopathy (BSE) belongs to a group of fatal, transmissible
      protein misfolding diseases known as transmissible spongiform encephalopathies
      (TSEs). All TSEs are caused by accumulation of misfolded prion protein (PrPSc)
      throughout the central nervous system (CNS), which results in neuronal loss and
      ultimately death. Like other protein misfolding diseases including Parkinson's
      disease and Alzheimer's disease, TSEs are generally not diagnosed until the onset
      of disease after the appearance of unequivocal clinical signs. As such,
      identification of the earliest clinical signs of disease may facilitate
      diagnosis. The retina is the most accessible part of the central nervous system,
      and retinal pathology in TSE affected animals has been previously reported. Here
      we describe antemortem changes in retinal function and morphology that are
      detectable in BSE inoculated animals several months (up to 11 months) prior to
      the appearance of any other signs of clinical disease. We also demonstrate that
      differences in the severity of these clinical signs reflect the amount of PrPSc
      accumulation in the retina and the resulting inflammatory response of the tissue.
      These results are the earliest reported clinical signs associated with TSE
      infection and provide a basis for understanding the pathology and evaluating
      therapeutic interventions. 

PMID- 25756288
TI  - Redefining fine roots improves understanding of below-ground contributions to
      terrestrial biosphere processes.
AB  - Fine roots acquire essential soil resources and mediate biogeochemical cycling in
      terrestrial ecosystems. Estimates of carbon and nutrient allocation to build and
      maintain these structures remain uncertain because of the challenges of
      consistently measuring and interpreting fine-root systems. Traditionally, fine
      roots have been defined as all roots <= 2 mm in diameter, yet it is now
      recognized that this approach fails to capture the diversity of form and function
      observed among fine-root orders. Here, we demonstrate how order-based and
      functional classification frameworks improve our understanding of dynamic root
      processes in ecosystems dominated by perennial plants. In these frameworks, fine
      roots are either separated into individual root orders or functionally defined
      into a shorter-lived absorptive pool and a longer-lived transport fine-root pool.
      Using these frameworks, we estimate that fine-root production and turnover
      represent 22% of terrestrial net primary production globally - a c. 30% reduction
      from previous estimates assuming a single fine-root pool. Future work developing
      tools to rapidly differentiate functional fine-root classes, explicit
      incorporation of mycorrhizal fungi into fine-root studies, and wider adoption of
      a two-pool approach to model fine roots provide opportunities to better
      understand below-ground processes in the terrestrial biosphere.

PMID- 25756287
TI  - Nitric oxide prevents alveolar senescence and emphysema in a mouse model.
AB  - Nomega-nitro-L-arginine methyl ester (L-NAME) treatment induces arteriosclerosis
      and vascular senescence. Here, we report that the systemic inhibition of nitric
      oxide (NO) production by L-NAME causes pulmonary emphysema. L-NAME-treated lungs
      exhibited both the structural (alveolar tissue destruction) and functional
      (increased compliance and reduced elastance) characteristics of emphysema
      development. Furthermore, we found that L-NAME-induced emphysema could be
      attenuated through both genetic deficiency and pharmacological inhibition of
      plasminogen activator inhibitor-1 (PAI-1). Because PAI-1 is an important
      contributor to the development of senescence both in vitro and in vivo, we
      investigated whether L-NAME-induced senescence led to the observed emphysematous
      changes. We found that L-NAME treatment was associated with molecular and
      cellular evidence of premature senescence in mice, and that PAI-1 inhibition
      attenuated these increases. These findings indicate that NO serves to protect and
      defend lung tissue from physiological aging. 

PMID- 25756289
TI  - Synthesis of aryl anti-vicinal diamines via aza-Brook rearrangement-initiated
      nucleophilic addition of alpha-silylamines to imines.
AB  - An efficient protocol is described for the synthesis of vicinal diamines via aza
      Brook rearrangement-initiated nucleophilic addition of alpha-silylamines to
      imines. Various symmetrical and unsymmetrical aryl diamine derivatives were
      prepared in moderate to high yields with high anti/syn diastereoselectivity. 

PMID- 25756290
TI  - Inventory of the GH70 enzymes encoded by Leuconostoc citreum NRRL B-1299 -
      identification of three novel alpha-transglucosylases.
AB  - Leuconostoc citreum NRRL B-1299 has long been known to produce alpha-glucans
      containing both alpha-(1->6) and alpha-(1->2) linkages, which are synthesized by
      alpha-transglucosylases of the GH70 family. We sequenced the genome of
      Leuconostoc citreum NRRL B-1299 to identify the full inventory of GH70 enzymes in
      this strain. Three new genes (brsA, dsrM and dsrDP) putatively encoding GH70
      enzymes were identified. The corresponding recombinant enzymes were
      characterized. Branching sucrase A (BRS-A) grafts linear alpha-(1->6) dextran
      with alpha-(1->2)-linked glucosyl units, and is probably involved in the alpha-(1
      >2) branching of L. citreum NRRL B-1299 dextran. This is the first report of a
      naturally occurring alpha-(1->2) branching sucrase. DSR-M and DSR-DP are
      dextransucrases that are specific for alpha-(1->6) linkage synthesis and mainly
      produce oligomers or short dextrans with molar masses between 580 and 27 000
      g.mol(-1) . In addition, DSR-DP contains sequences that diverge from the
      consensus sequences that are typically present in enzymes that synthesize linear
      dextran. Comparison of the genome with five other L. citreum genomes further
      revealed that dsrDP is unique to L. citreum NRRL B-1299. The presence of this
      gene in a prophage represents the first evidence of phage-mediated horizontal
      transfer of genes encoding such enzymes in lactic acid bacteria. Finally, brsA
      and dsrM are located in a chromosomal region in which genes encoding strain
      specific GH70 enzymes are consistently located. This region may be a good target
      on which to focus in order to rapidly evaluate the diversity of GH70 enzymes in
      L. citreum strains.

PMID- 25756291
TI  - Yeast Golden Gate (yGG) for the Efficient Assembly of S. cerevisiae Transcription
      Units.
AB  - We have adapted the Golden Gate DNA assembly method to the assembly of
      transcription units (TUs) for the yeast Saccharomyces cerevisiae, in a method we
      call yeast Golden Gate (yGG). yGG allows for the easy assembly of TUs consisting
      of promoters (PRO), coding sequences (CDS), and terminators (TER). Carefully
      designed overhangs exposed by digestion with a type IIS restriction enzyme enable
      virtually seamless assembly of TUs that, in principle, contain all of the
      information necessary to express a gene of interest in yeast. We also describe a
      versatile set of yGG acceptor vectors to be used for TU assembly. These vectors
      can be used for low or high copy expression of assembled TUs or integration into
      carefully selected innocuous genomic loci. yGG provides synthetic biologists and
      yeast geneticists with an efficient new means by which to engineer S. cerevisiae.

PMID- 25756292
TI  - Bristles before down: a new perspective on the functional origin of feathers.
AB  - Over the course of the last two decades, the understanding of the early evolution
      of feathers in nonavian dinosaurs has been revolutionized. It is now recognized
      that early feathers had a simple form comparable in general structure to the
      hairs of mammals. Insight into the prevalence of simple feathers throughout the
      dinosaur family tree has gradually arisen in tandem with the growing evidence for
      endothermic dinosaur metabolisms. This has led to the generally accepted opinion
      that the early feather coats of dinosaurs functioned as thermo insulation.
      However, thermo insulation is often erroneously stated to be a likely functional
      explanation for the origin of feathers. The problem with this explanation is
      that, like mammalian hair, simple feathers could serve as insulation only when
      present in sufficiently high concentrations. The theory therefore necessitates
      the origination of feathers en masse. We advocate for a novel origin theory of
      feathers as bristles. Bristles are facial feathers common among modern birds that
      function like mammalian tactile whiskers, and are frequently simple and hair-like
      in form. Bristles serve their role in low concentrations, and therefore offer a
      feasible first stage in feather evolution.

PMID- 25756293
TI  - The Odense Child Cohort: aims, design, and cohort profile.
AB  - BACKGROUND: The importance of the environment on the development of the fetus and
      infant throughout early life is increasingly recognised. To study such effects,
      biological samples and accurate data records are required. Based on multiple data
      collection from a healthy pregnant population, the Odense Childhood Cohort (OCC)
      study aims to provide new information about the environmental impact on child
      health by sequential follow-up to 18 years of age among children born between
      2010 and 2012. METHODS: A total of 2874 of 6707 pregnancies (43%) were recruited
      between January 2010 and December 2012. Three hundred seventy-four have since
      left the study, leaving 2500 active families. The non-participants act as
      controls contributing data through local registries. Biological material,
      questionnaires, and registry data were compiled. Anthropometric data and other
      physical data were collected. RESULTS: Two thousand five hundred families
      actively participated in the study with 2549 children. Sixty-four per cent of the
      fathers and 60% and 58% of the mothers, respectively, donated a blood sample at
      10 and 28 weeks of gestation. On average, 69% completed questionnaires, 78% of
      the children were regularly examined, and had a blood sample taken (46%). The
      participating pregnant women differed from the non-participants in several
      respects: age, body mass index, smoking, parity, education, and ethnicity. The
      infants were comparable with respect to gender and mode of delivery. CONCLUSIONS:
      The OCC provides material for in-depth analysis of environmental and genetic
      factors that are important for child health and disease. Registry data from non
      participating women and infants are available which ensures a high degree of
      comparable data.

PMID- 25756294
TI  - Community pharmacists' role in benzodiazepine supply in Ireland: a questionnaire
      of pharmacists' views and experiences.
AB  - OBJECTIVE: To investigate the views and experiences of community pharmacists in
      Ireland regarding their role in benzodiazepine supply and the potential for role
      expansion. METHODS: A postal questionnaire was issued to a random, geographically
      stratified sample of community pharmacies in Ireland. KEY FINDINGS: The response
      rate was 37.6%. Pharmacists' awareness of the national source of benzodiazepine
      guidelines was low (26.6% previously aware). Benzodiazepine prescriptions were
      frequently encountered in practice and commonly for extended durations of 28
      days. Pharmacists' involvement in roles extending beyond dispensing was limited.
      In the 6 months prior to the questionnaire, fewer than half of pharmacists
      reported having suggested discontinuation to a patient (43.7%) or having
      contacted a prescriber about a patient's benzodiazepine use (47.1%). Pharmacists
      acknowledged their potential to undertake a more extensive role in benzodiazepine
      supply and expressed willingness to do so in practice. CONCLUSIONS: This study
      adds to the limited body of existing literature regarding community pharmacists'
      role in benzodiazepine supply. The findings indicate the need to revisit existing
      benzodiazepine guidelines to improve pharmacists' awareness of them and to
      address long-term prescribing. The apparent lack of active pharmacist involvement
      in roles and activities extending beyond dispensing needs to be addressed. Given
      that most pharmacists encountered benzodiazepine prescriptions at least once
      daily in practice, they are well positioned to promote safe and appropriate
      benzodiazepine use. Sizeable proportions of pharmacists expressed willingness to
      expand upon their existing role and facilitate long-term patients in attempting
      discontinuation. Further research is needed to explore barriers and facilitators
      to pharmacists undertaking extended roles in benzodiazepine supply in greater
      detail.

PMID- 25756295
TI  - Modelling psychiatric disability.
AB  - RATIONALE, AIMS AND OBJECTIVES: There has been inadequate philosophical attention
      to the claims of psychiatric user/survivor activist groups, although these groups
      represent a significant social justice movement. Many of the core concerns and
      claims emerging from this activism can be found in disability activism. A first
      step that must be taken is to question how mental illnesses are modelled.
      Biomedical modelling is heavily criticized by psychiatric users/survivors for
      being reductionistic and for perpetuating damaging presumptions about decline and
      pathology. Social constructionist modelling, on the other hand, tends to be
      overly dismissive of biological factors that are often at play with these sorts
      of impairments. A middle-ground approach, interactionist modelling, promises to
      be responsive to demands for recognition from psychiatric users/survivors.
      METHOD: I will first outline the core commitments of psychiatric users/survivors.
      Next, I will evaluate different models for mental illness by bringing together
      insights from user/survivor and disability activism. CONCLUSIONS: I conclude that
      interactionist modelling holds the best hope for supporting shared decision
      making. This type of model braids together the expertise of patients and medical
      professionals.

PMID- 25756296
TI  - Essential oils in the management of the donkey louse, Bovicola ocellatus.
AB  - REASONS FOR PERFORMING STUDY: Chewing lice are widespread and clinically
      compromising parasites of livestock and equids. Their management is complicated
      by growing levels of resistance to commonly applied insecticides. Hence, the
      development of novel approaches to their control is of major clinical interest.
      OBJECTIVES: To assess the effects of incorporating the essential oils of tea tree
      and lavender into a grooming programme for populations of donkeys with natural
      infestations of Bovicola ocellatus in the UK and Ireland when louse populations
      were at their winter seasonal peak. STUDY DESIGN: In vivo field trial. METHODS:
      Suspensions of 5% (v/v) tea tree or lavender oil or an excipient only control
      were groomed into the coats of winter-housed donkeys (n = 198) on 2 occasions, 2
      weeks apart. Louse counts were conducted before each application and 2 weeks
      later. RESULTS: After 2 applications, the groups groomed with lavender or tea
      tree oil suspensions had a significant reduction in louse intensity, with a mean
      decline in louse abundance of 78% (95% confidence interval 76-80%). Louse numbers
      in the groups groomed with excipient only either did not change or increased
      significantly. Donkey hair length had no effect on the decline in louse numbers.
      CONCLUSIONS: These results demonstrate that the inclusion of essential oil
      suspensions during grooming can be used to manage louse populations successfully.

PMID- 25756297
TI  - Imaging three-dimensional surface objects with submolecular resolution by atomic
      force microscopy.
AB  - Submolecular imaging by atomic force microscopy (AFM) has recently been
      established as a stunning technique to reveal the chemical structure of unknown
      molecules, to characterize intramolecular charge distributions and bond ordering,
      as well as to study chemical transformations and intermolecular interactions. So
      far, most of these feats were achieved on planar molecular systems because high
      resolution imaging of three-dimensional (3D) surface structures with AFM remains
      challenging. Here we present a method for high-resolution imaging of nonplanar
      molecules and 3D surface systems using AFM with silicon cantilevers as force
      sensors. We demonstrate this method by resolving the step-edges of the (101)
      anatase surface at the atomic scale by simultaneously visualizing the structure
      of a pentacene molecule together with the atomic positions of the substrate and
      by resolving the contour and probe-surface force field on a C60 molecule with
      intramolecular resolution. The method reported here holds substantial promise for
      the study of 3D surface systems such as nanotubes, clusters, nanoparticles,
      polymers, and biomolecules using AFM with high resolution. 

PMID- 25756298
TI  - Stabilizing coordinated radicals via metal-ligand covalency: a structural,
      spectroscopic, and theoretical investigation of group 9 tris(dithiolene)
      complexes.
AB  - Proper assignment of redox loci in coordination complexes with redox-active
      ligands to either the metal or the ligand is essential for rationalization of
      their chemical reactivity. However, the high covalency endemic to complexes of
      late, third-row transition metals complicates such assignments. Herein, we
      systematically explore the redox behavior of a series of group 9 tris(dithiolene)
      complexes, [M(mnt)3]3- (M = Ir, Rh, Co; mnt = maleonitriledithiolate). The Ir
      species described comprise the first examples of homoleptic Ir dithiolene
      complexes. The enhanced metal-ligand covalency of the Ir-S interaction leads to
      remarkable reactivity of [Ir(mnt)3]3- and stabilization of mononuclear
      [Ir(mnt)3]2- complex ions as well as dimerized versions featuring weak, covalent,
      intermolecular S-S bonds. The dianionic Rh and Co analogues are, in contrast,
      highly unstable, resulting in the rapid formation of [Rh2(mnt)5]4- and
      [Co(mnt)2]22-, respectively. The synthesized complexes were studied by single
      crystal X-ray diffraction, X-ray absorption spectroscopy, optical spectroscopy,
      magnetometry, density functional theory, and spectroscopy-oriented configuration
      interaction calculations. Spectroscopic and theoretical analyses suggest that the
      stability of [Ir(mnt)3]2- may be attributed to dilution of ligand radical
      character by a high degree of Ir 5d character in the singly occupied molecular
      orbital.

PMID- 25756300
TI  - Chemically-Modified Peptides Targeting the PDZ Domain of GIPC as a Therapeutic
      Approach for Cancer.

PMID- 25756299
TI  - Cucurbitacin D Is a Disruptor of the HSP90 Chaperone Machinery.
AB  - Heat shock protein 90 (Hsp90) facilitates the maturation of many newly
      synthesized and unfolded proteins (clients) via the Hsp90 chaperone cycle, in
      which Hsp90 forms a heteroprotein complex and relies upon cochaperones,
      immunophilins, etc., for assistance in client folding. Hsp90 inhibition has
      emerged as a strategy for anticancer therapies due to the involvement of clients
      in many oncogenic pathways. Inhibition of chaperone function results in client
      ubiquitinylation and degradation via the proteasome, ultimately leading to tumor
      digression. Small molecule inhibitors perturb ATPase activity at the N-terminus
      and include derivatives of the natural product geldanamycin. However, N-terminal
      inhibition also leads to induction of the pro-survival heat shock response (HSR),
      in which displacement of the Hsp90-bound transcription factor, heat shock factor
      1, translocates to the nucleus and induces transcription of heat shock proteins,
      including Hsp90. An alternative strategy for Hsp90 inhibition is disruption of
      the Hsp90 heteroprotein complex. Disruption of the Hsp90 heteroprotein complex is
      an effective strategy to prevent client maturation without induction of the HSR.
      Cucurbitacin D, isolated from Cucurbita texana, and 3-epi-isocucurbitacin D
      prevented client maturation without induction of the HSR. Cucurbitacin D also
      disrupted interactions between Hsp90 and two cochaperones, Cdc37 and p23. 

PMID- 25756301
TI  - Inoculum selection influences the biochemical methane potential of agro
      industrial substrates.
AB  - Obtaining a reliable estimation of the methane potential of organic waste streams
      in anaerobic digestion, for which a biochemical methane potential (BMP) test is
      often used, is of high importance. Standardization of this BMP test is required
      to ensure inter-laboratory repeatability and accuracy of the BMP results.
      Therefore, guidelines were set out; yet, these do not provide sufficient
      information concerning origin of and the microbial community in the test
      inoculum. Here, the specific contribution of the methanogenic community on the
      BMP test results was evaluated. The biomethane potential of four different
      substrates (molasses, bio-refinery waste, liquid manure and high-rate activated
      sludge) was determined by means of four different inocula from full-scale
      anaerobic digestion plants. A significant effect of the selected inoculum on the
      BMP result was observed for two out of four substrates. This inoculum effect
      could be attributed to the abundance of methanogens and a potential inhibiting
      effect in the inoculum itself, demonstrating the importance of inoculum selection
      for BMP testing. We recommend the application of granular sludge as an inoculum,
      because of its higher methanogenic abundance and activity, and protection from
      bulk solutions, compared with other inocula. 

PMID- 25756303
TI  - Supplementation of a standardized extract from Phyllanthus emblica improves
      cardiovascular risk factors and platelet aggregation in overweight/class-1 obese
      adults.
AB  - The objective of this study (clinicaltrials.gov NCT01858376) was to determine the
      effect of oral supplementation of a standardized extract of Phyllanthus emblica
      (CAPROS((r))) on cardiovascular disease (CVD) risk factors in overweight adult
      human subjects from the US population. Overweight/Class-1 obese (body-mass index:
      25-35) adult subjects received 500 mg of CAPROS supplement b.i.d for 12 weeks.
      The study design included two baseline visits followed by 12 weeks of
      supplementation and then 2 weeks of washout. At all visits, peripheral venous
      blood was collected in sodium citrate tubes. Lipid profile measurements
      demonstrated a significant decrease in calculated low-density lipoprotein
      cholesterol and total cholesterol/high-density lipoprotein following 12 weeks of
      CAPROS supplementation when compared to averaged baseline visits. Circulatory
      high-sensitivity C reactive protein (hs-CRP) levels were significantly decreased
      after 12 weeks of supplementation. In addition, both ADP- and collagen-induced
      platelet aggregation was significantly downregulated following 12 weeks of
      supplementation. Overall, the study suggests that oral CAPROS supplementation may
      provide beneficial effects in overweight/Class-1 obese adults by lowering
      multiple global CVD risk factors. 

PMID- 25756304
TI  - Injection molded polymeric micropatterns for bone regeneration study.
AB  - An industrially feasible process for the fast mass-production of molded polymeric
      micro-patterned substrates is here presented. Microstructured polystyrene (PS)
      surfaces were obtained through micro injection molding (MUIM) technique on
      directly patterned stamps realized with a new zirconia-based hybrid spin-on
      system able to withstand 300 cycles at 90  degrees C. The use of directly
      patterned stamps entails a great advantage on the overall manufacturing process
      as it allows a fast, flexible, and simple one-step process with respect to the
      use of milling, laser machining, electroforming techniques, or conventional
      lithographic processes for stamp fabrication. Among the different obtainable
      geometries, we focused our attention on PS replicas reporting 2, 3, and 4 MUm
      diameter pillars with 8, 9, 10 MUm center-to-center distance, respectively. This
      enabled us to study the effect of the substrate topography on human mesenchymal
      stem cells behavior without any osteogenic growth factors. Our data show that
      microtopography affected cell behavior. In particular, calcium deposition and
      osteocalcin expression enhanced as diameter and interpillar distance size
      increases, and the 4-10 surface was the most effective to induce osteogenic
      differentiation. 

PMID- 25756306
TI  - Drop coating deposition Raman spectroscopy of blood plasma for the detection of
      colorectal cancer.
AB  - We have recently applied the technique of drop coating deposition Raman (DCDR)
      spectroscopy for colorectal cancer (CRC) detection using blood plasma. The aim of
      this study was to develop a more convenient and stable method based on blood
      plasma for noninvasive CRC detection. Significant differences are observed in
      DCDR spectra between healthy (n = 105) and cancer (n = 75) plasma from 15 CRC
      patients and 21 volunteers, particularly in the spectra that are related to
      proteins, nucleic acids, and beta-carotene. The multivariate analysis principal
      components analysis and the linear discriminate analysis, together with leave-one
      out, cross validation were used on DCDR spectra and yielded a sensitivity of 100%
      (75/75) and specificity of 98.1% (103/105) for detection of CRC. This study
      demonstrates that DCDR spectroscopy of blood plasma associated with multivariate
      statistical algorithms has the potential for the noninvasive detection of CRC.

PMID- 25756305
TI  - Role of mecp2 in experience-dependent epigenetic programming.
AB  - Mutations in the X-linked gene MECP2, the founding member of a family of proteins
      recognizing and binding to methylated DNA, are the genetic cause of a devastating
      neurodevelopmental disorder in humans, called Rett syndrome. Available evidence
      suggests that MECP2 protein has a critical role in activity-dependent neuronal
      plasticity and transcription during brain development. Moreover, recent studies
      in mice show that various posttranslational modifications, notably
      phosphorylation, regulate Mecp2's functions in learning and memory, drug
      addiction, depression-like behavior, and the response to antidepressant
      treatment. The hypothalamic-pituitary-adrenal (HPA) axis drives the stress
      response and its deregulation increases the risk for a variety of mental
      disorders. Early-life stress (ELS) typically results in sustained HPA-axis
      deregulation and is a major risk factor for stress related diseases, in
      particular major depression. Interestingly, Mecp2 protein has been shown to
      contribute to ELS-dependent epigenetic programming of Crh, Avp, and Pomc, all of
      these genes enhance HPA-axis activity. Hereby ELS regulates Mecp2
      phosphorylation, DNA binding, and transcriptional activities in a tissue-specific
      and temporospatial manner. Overall, these findings suggest MECP2 proteins are so
      far underestimated and have a more dynamic role in the mediation of the gene
      environment dialog and epigenetic programming of the neuroendocrine stress system
      in health and disease. 

PMID- 25756307
TI  - Differential in vivo urodynamic measurement in a single thin catheter based on
      two optical fiber pressure sensors.
AB  - Urodynamic analysis is the predominant method for evaluating dysfunctions in the
      lower urinary tract. The exam measures the pressure during the filling and
      voiding process of the bladder and is mainly interested in the contraction of the
      bladder muscles. The data arising out of these pressure measurements enables the
      urologist to arrive at a precise diagnosis and prescribe an adequate treatment. A
      technique based on two optical fiber pressure and temperature sensors with a
      resolution of better than 0.1 cm H2O (~10 Pa), a stability better than 1 cm
      H2O/hour, and a diameter of 0.2 mm in a miniature catheter with a diameter of
      only 5 Fr (1.67 mm), was used. This technique was tested in vivo on four patients
      with a real-time urodynamic measurement system. The optical system presented
      showed a very good correlation to two commercially available medical reference
      sensors. Furthermore, the optical urodynamic system demonstrated a higher dynamic
      and better sensitivity to detect small obstructions than both pre-existing
      medical systems currently in use in the urodynamic field.

PMID- 25756308
TI  - Increased Dose of Inhaled Corticosteroid versus Add-On Long-acting beta-Agonist
      for Step-Up Therapy in Asthma.
AB  - RATIONALE: Guidelines advocate adding long-acting beta-agonist (LABA) to inhaled
      corticosteroid as the preferred step-up therapy to increasing inhaled
      corticosteroid dose for patients with uncontrolled asthma on inhaled
      corticosteroid monotherapy. However, less than 5% of patients with asthma qualify
      for the randomized controlled trials on which guidelines are based. Thus, real
      world data are needed to complement the results of randomized trials with narrow
      entry criteria. OBJECTIVES: To compare the effectiveness of stepping up asthma
      therapy with an increased dose of various types of inhaled corticosteroid as
      compared with add-on LABA. METHODS: We performed a historical matched cohort
      study using large primary care databases to compare asthma step-up therapy with
      small- and standard size-particle inhaled corticosteroid versus added LABA for
      patients 12-80 years old. As outcomes, we examined a composite of asthma control
      and rates of severe exacerbations. MEASUREMENTS AND MAIN RESULTS: The odds of
      asthma control and rates of severe exacerbations over one outcome year were
      comparable with increased inhaled corticosteroid dose versus added LABA. The
      adjusted odds ratios (95% confidence interval) for achieving asthma control with
      increased inhaled corticosteroid dose versus inhaled corticosteroid/LABA were
      0.99 (0.88-1.12) for small-particle inhaled corticosteroid (n = 3,036 per cohort)
      and 0.85 (0.67-1.07) for standard size-particle inhaled corticosteroid (n = 809
      per cohort). The adjusted rate ratios (95% confidence interval) for severe
      exacerbations, compared with inhaled corticosteroid/LABA combination inhaler,
      were 1.04 (0.91-1.20) and 1.18 (0.92-1.54), respectively. The results were not
      affected by smoking status. CONCLUSIONS: When applied to a broad primary care
      population, antiinflammatory therapy using increased doses of small- or standard
      size-particle inhaled corticosteroid is as effective as adding LABA, as measured
      by outcomes important to both patients and providers. Real-world populations and
      outcomes need to be taken into consideration when formulating treatment
      recommendations.

PMID- 25756310
TI  - Transcriptional and metabolic effects of glucocorticoid receptor alpha and beta
      signaling in zebrafish.
AB  - In humans and zebrafish, 2 glucocorticoid (GC) receptor (GR) splice variants
      exist: the canonical GR alpha-isoform (GRalpha), and the GRbeta. In the present
      study, we have used the zebrafish model system in order to reveal genes affected
      by each of these 2 receptor isoforms. By injecting zebrafish embryos with
      different splice-blocking morpholinos, we could knock down both GR isoforms or
      could target the alternative splicing of the GR pre-mRNA in favor of the GRbeta.
      In addition, specific GRbeta overexpression was achieved by injecting mRNA.
      Embryos were treated with the synthetic GC dexamethasone, and transcriptome
      analysis was performed. Two distinct gene clusters were found that were regulated
      by GRalpha: one that was regulated by GRalpha under basal conditions (presence of
      endogenous cortisol only), and one that was regulated upon increased activation
      of GRalpha (using a pharmacological dose of dexamathasone). GRbeta may act as a
      dominant-negative inhibitor of GRalpha when GRbeta is overexpressed and the
      GRalpha expression level is knocked down simultaneously. However, without GRalpha
      knockdown, no evidence for this activity was found. In addition, the data
      indicate regulation of gene transcription through other mechanisms of action by
      GRbeta. We also investigated the concentrations of several metabolites using
      nuclear magnetic resonance spectroscopy. We found that dexamethasone treatment
      and knockdown of GRalpha together with overexpression of GRbeta had opposite
      effects on glucose, amino acid, and fatty acid levels. Thus, we have shed new
      light on the molecular mechanisms of GC-induced effects on metabolism, which are
      known to increase the risk of obesity, hyperglycemia, and diabetes. 

PMID- 25756309
TI  - Kisspeptin regulation of arcuate neuron excitability in kisspeptin receptor
      knockout mice.
AB  - The G protein-coupled receptor 54 (GPR54) is critical for kisspeptin to activate
      GnRH neurons to modulate fertility. However, the often mismatching distribution
      of kisspeptin and GPR54 in the brain suggests that kisspeptin may also act on
      other receptors. The arcuate nucleus (ARN) is one brain region with a very high
      density of kisspeptin fibers but only limited evidence for the expression of
      GPR54. Using acute brain slice electrophysiology in combination with Gpr54
      knockout (GPR54KO) mouse models, we examined whether actions of kisspeptin in the
      ARN were dependent upon GPR54. Cell-attached recordings from unidentified ARN
      neurons in wild-type mice revealed that approximately one third of neurons were
      either excited or inhibited by kisspeptin in a dose-dependent manner. The
      responses of ARN neurons to kisspeptin were exactly the same in GPR54KO mice
      despite effects of kisspeptin on GnRH neurons being abolished. To evaluate
      whether kisspeptin may be acting through neuropeptide FF receptors, the effects
      of an agonist RFamide-related peptide 3 (RFRP-3) and antagonists RF9 and BIBP
      3226 were evaluated. Both the excitatory and inhibitory effects of kisspeptin
      were mimicked by the agonist RFRP-3. RF9 itself activated ARN neurons and
      suppressed only the inhibitory actions of kisspeptin. BIBP-3226 suppressed
      kisspeptin actions in 50% of neurons. Whole-cell recordings in GPR54KO mice
      demonstrated that both kisspeptin and RFRP-3 acted directly on the same ARN
      neurons and activated the same ion channels. Together, these studies demonstrate
      that kisspeptin can act partly through neuropeptide FF receptors to modulate
      neuronal activity independent of GPR54 in the mouse brain. 

PMID- 25756311
TI  - Identification of Fetal Inflammatory Cells in Eosinophilic/T-cell Chorionic
      Vasculitis Using Fluorescent In Situ Hybridization.
AB  - Eosinophilic/T-cell chorionic vasculitis (ETCV) is an inflammatory lesion of
      placental fetal vessels. In contrast to acute chorionic vasculitis, inflammation
      in ETCV is seen in chorionic vessel walls opposite the amnionic surface. It is
      not known whether inflammation in ETCV consists of maternal cells from the
      intervillous space or fetal cells migrating from the vessel. We used fluorescent
      in situ hybridization (FISH) to differentiate fetal versus maternal cells in
      ETCV. Placentas with ETCV, previously identified for a published study, were
      used. Infant sex in each case was identified using the electronic medical record.
      For male infants, 3-MUm sections were cut from archived tissue blocks from
      placentas involving ETCV and stained with fluorescent X- and Y-chromosome
      centromeric probes. A consecutive hematoxylin/eosin-stained section was used for
      correlation. FISH analysis was performed on 400 interphase nuclei at the site of
      ETCV to determine the proportion of XX, XY, X, and Y cells. Of 31 ETCV cases, 20
      were female and 10 were male (1 sex not recorded). Six of 10 cases with male
      infants had recuts with visible ETCV. In these 6 cases the average percentages
      (ranges) of XY cells, X-only cells, and Y-only cells in the region of
      inflammation were 81 (70-90), 11 (6-17), and 8 (2-14), respectively. There was a
      2:1 female:male infant ratio in ETCV. Similar to acute chorionic vasculitis, the
      inflammation in ETCV is of fetal origin. It is still unknown, however, whether
      the stimulus for ETCV is of fetal or maternal origin. 

PMID- 25756312
TI  - Lack of Effect of Typical Rapid-Weight-Loss Practices on Balance and Anaerobic
      Performance in Apprentice Jockeys.
AB  - Balance and anaerobic performance are key attributes related to horse-racing
      performance, but research on the impact of making weight for racing on these
      parameters remains unknown. The purpose of this study was to investigate the
      effects of rapid weight loss in preparation for racing on balance and anaerobic
      performance in a group of jockeys. METHODS: Twelve apprentice male jockeys and 12
      age- and gender-matched controls completed 2 trials separated by 48 h. In both
      trials, body mass, hydration status, balance, and anaerobic performance were
      assessed. Between the trials, the jockeys reduced body mass by 4% using weight
      loss methods typically adopted in preparation for racing, while controls
      maintained body mass through typical daily dietary and physical activity habits.
      RESULTS: Apprentice jockeys decreased mean body mass by 4.2% +/- 0.3% (P < .001)
      with a subsequent increase in dehydration (P < .001). The controls maintained
      body mass and a euhydrated state. No differences in balance, on the left or right
      side, or in peak power, mean power, or fatigue index were reported between the
      trials in either group. CONCLUSION: Results from this study indicate that a 4%
      reduction in body mass in 48 h through the typical methods employed for racing,
      in association with an increase in dehydration, resulted in no impairments in
      balance or anaerobic performance. Further research is required to evaluate
      performance in a sport-specific setting and to investigate the specific
      physiological mechanisms involved.

PMID- 25756313
TI  - Pacing Strategy in Short Cycling Time Trials.
AB  - PURPOSE: To reach top performance in cycling, optimizing distribution of energy
      resources is crucial. The purpose of this study was to investigate power output
      during 250-m, 500-m, and 1000-m cycling time trials and the characteristics of
      the adopted pacing strategy. METHODS: Nine trained cyclists completed an
      incremental test and 3 time trials that they were instructed to finish as quickly
      as possible. Preceding the trials, peak power during short sprints (PP sprint)
      and gross efficiency (GE) were measured. During the trials, power output and
      oxygen consumption were measured to calculate the contribution of the aerobic and
      anaerobic energy sources. After the trial GE was measured again. RESULTS: Peak
      power during all trials (PPTT) was lower than PP sprint. In the 250-m trial the
      PPTT was higher in the 1000-m trial (P = .008). The subjects performed a
      significantly longer time at high intensity in the 250-m than in the 1000-m (P =
      .029). GE declined significantly during all trials (P < .01). Total anaerobically
      attributable work was less in the 250-m than in the 500-m (P = .015) and 1000-m
      (P < .01) trials. CONCLUSION: The overall pacing pattern in the 250-m trial
      appears to follow an all-out strategy, although peak power is still lower than
      the potential maximal power output. This suggests that a true all-out pattern of
      power output may not be used in fixed-distance events. The 500-m and 1000-m had a
      more conservative pacing pattern and anaerobic power output reached a constant
      magnitude.

PMID- 25756315
TI  - Palladium-catalyzed intramolecular cyclization of ynamides: synthesis of 4-halo
      oxazolones.
AB  - A mild and efficient methodology involving Pd(PPh3)4-catalyzed intramolecular
      cyclization of N-alkynyl alkyloxycarbamates with CuCl2 or CuBr2 for the synthesis
      of 4-halo-oxazolones was developed. This reaction exhibiting good functional
      tolerance provided a new, efficient, and rapid synthetic process to 4-halo
      oxazolones. The resulting 4-halo-oxazolones can serve as great potential
      precursors for the 3,4,5-trisubstituted oxazolones via a Pd-catalyzed cross
      coupling reaction. 

PMID- 25756316
TI  - Effects of parenting role and parent-child interaction on infant motor
      development in Taiwan Birth Cohort Study.
AB  - BACKGROUND: Previous studies have rarely focused on healthy infants' motor
      development, and nationwide birth cohort studies in Taiwan are limited. It has
      been shown that parent-child interactions significantly influence infant motor
      development and the effect of mother-infant attachment on infant development is
      stronger than father-infant attachment. However, it is not well understood that
      whether the mother-infant or father-infant interaction has the confounding effect
      on infant motor development. AIMS: To understand healthy infant motor development
      in Taiwan; and to investigate the effects of parenting roles and parent-child
      interactions on infant motor development. METHODS: Data were derived from the 1st
      through the 2nd waves of the Taiwan Birth Cohort Study-Pilot Database. Infants
      were classified into two categories (complete or incomplete development)
      according to their developmental milestones. Generalized estimating equations
      (GEE) and random effects models were used to clarify the possible long-term
      effects. RESULTS: The rate of infants who completed development in 6 months was
      30.50%; however the rate was increased in 18 month-old children (80.01%). A
      mother's perceived infant care competence was the most important factor for
      infant motor development. "Whether or not the infant was the only baby in the
      family" and "parent-child interaction" had slightly significant effect on infant
      motor development. CONCLUSIONS: In conclusion, the mother's perceived competence
      must be strengthened and parent-infant interactions should be emphasized on a
      daily basis.

PMID- 25756317
TI  - The stature of the self-employed and its relation with earnings and satisfaction.
AB  - Taller individuals have on average a higher socio-economic status than shorter
      individuals. In countries where entrepreneurs have high social status, we may
      therefore expect that entrepreneurs are taller than wage workers. Using data from
      the German Socio-Economic Panel (2002-2012), we find that a 1cm increase in an
      individual's height raises the probability of being self-employed (the most
      common proxy for entrepreneurship) versus paid employed by 0.15 percentage
      points. Within the self-employed, the probability of being an employer is
      increased by 0.10 percentage points as a result of a 1cm increase in height,
      whereas this increase is 0.05 percentage points for an own-account worker. This
      result corroborates the higher social status of employers compared to own-account
      workers. We find a height premium in earnings for self-employed and paid-employed
      individuals: an additional 1cm in height is associated with a 0.39% increase in
      hourly earnings for paid employees and a 0.52% increase for self-employed
      individuals. Our analysis reveals that approximately one third of the height
      premium in earnings is explained by differences in educational attainment. We
      also establish the existence of a height premium in terms of work and life
      satisfaction, which is more pronounced for paid employees than for self-employed
      individuals. 

PMID- 25756318
TI  - Can physical activity be used as a tool to reduce depression in patients after a
      cardiac event? What is the evidence? A systematic literature study.
AB  - A reduction in the incidence of cardiovascular diseases (CVD) has been reported
      in the Western world, but post-infarction depression often occurs and is related
      to poor medical outcomes. The aim of this study was to examine the scientific
      literature by a systematic review, in order to find evidence for whether physical
      activity can be a tool to reduce depression in patients who have suffered a
      cardiac event. Three databases were systematically searched (PubMed, CINAHL, and
      Cochrane), and the GRADE protocol was used in combination with a revised Amstar
      protocol for the systematic review. Scientific reports fitting the area were
      scarce. Finally, ten studies were included in this study: one meta-analysis, five
      randomized controlled trials, and four clinical trials. The results showed low to
      moderate evidence for the use of low to moderate levels of exercise as a tool to
      reduce depression in post-coronary artery event patients. This study concluded
      positive effects of physical activity as a tool to reduce depression in post
      coronary artery event patients. Physiotherapists could be further involved in
      increasing physical activity after cardiac events. More studies are needed in the
      area. 

PMID- 25756321
TI  - Early-Phase Satellite Cell and Myonuclear Domain Adaptations to Slow-Speed vs.
      Traditional Resistance Training Programs.
AB  - The purpose of this investigation was to identify adaptations in satellite cell
      (SC) content and myonuclear domain (MND) after 6-week slow-speed vs. "normal
      speed" resistance training programs. Thirty-four untrained females were divided
      into slow speed (SS), traditional strength (TS), traditional muscular endurance
      (TE), and nontraining control (C) groups. Three sets each of leg press, squat,
      and knee extension were performed 2 days per week for the first week and 3 days
      per week for the following 5 weeks. The SS group performed 6-10 repetition
      maximum (6-10RM) for each set with 10-second concentric (con) and 4-second
      eccentric (ecc) contractions for each repetition. Traditional strength and TE
      performed 6-10RM and 20-30RM, respectively, at "normal" speed (1-2 seconds per
      con and ecc contractions). Traditional muscular endurance and SS trained at the
      same intensity (40-60% 1RM), whereas TS trained at 80-85% 1RM. Pretraining and
      posttraining muscle biopsies were analyzed for fiber cross-sectional area, fiber
      type, SC content, myonuclear number, and MND. Satellite cell content of type I,
      IIA, IIAX, and IIX fibers significantly increased in TS. However, SC content of
      only type IIAX and IIX fibers increased in SS, and there was no change in TE or
      C. Myonuclear number did not change in any group. Myonuclear domain of type I,
      IIA, IIAX, and IIX fibers increased in TS, whereas MND of only type IIA fibers
      increased in SS, and there was no change in TE or C. In conclusion, slow-speed
      resistance training increased SC content and MND more than training with a
      similar resistance at normal speed. However, high-intensity normal-speed training
      produced the greatest degree of fiber adaptation for each variable.

PMID- 25756320
TI  - The Current Status of Nurse-Administered Propofol Sedation in Endoscopy: An
      Evidence-Based Practice Nurse Fellowship Project.
AB  - The Society for Gastroenterology Nurses and Associates (SGNA) launched a nurse
      fellowship program in 2011 to promote evidence-based practice. Each accepted
      applicant was challenged to select a relevant topic, explore the current
      research, and translate this information to daily practice. The author, an SGNA
      Fellow, selected the topic, nurse-administered propofol sedation, that has been a
      prevailing subject in endoscopy for many years. A significant amount of
      literature has been written on the drug's safety and efficacy. This article
      explores a brief history of the practice and the future of this controversial
      drug for procedural sedation. A review of current literature is explored with an
      emphasis on the past 5 years as well as a discussion on regulatory limitations
      that have been placed on the practice of non-anesthesiologist-administered
      propofol sedation. 

PMID- 25756322
TI  - Aerobic capacity is associated with improved repeated shift performance in
      hockey.
AB  - Current research has found conflicting results regarding the relationship between
      maximal oxygen uptake ((Equation is included in full-text article.)) and the
      repeated sprint ability (RSA) of hockey players. The purpose of this study was to
      use sport-specific testing methods to investigate this relationship. Forty-five
      (range, 18-24) college hockey players completed a graded exercise test on a
      skating treadmill to ascertain their (Equation is included in full-text
      article.). An on-ice repeated shift test was then conducted to evaluate each
      player's susceptibility to fatigue. First gate, second gate, and total test times
      were collected on the course and then used to calculate associated decrement
      scores. Second gate decrement was significantly correlated to (Equation is
      included in full-text article.)(r = -0.31, p = 0.04). Final stage completed
      during the graded exercise test was also significantly correlated to second gate
      and total decrement (r = -0.46, p = 0.001; r = -0.32, p = 0.03). No significant
      correlation was found between either first gate or total decrement score and
      (Equation is included in full-text article.)(r = -0.11, p = 0.46; r = -0.17, p =
      0.26). The results of this study indicate that RSA is associated with (Equation
      is included in full-text article.)and final stage completed when using sport
      specific testing methods.

PMID- 25756323
TI  - Time-to-Fatigue During Incline Treadmill Running: Implications for Individualized
      Training Prescription.
AB  - Uphill running has been touted as a key interval training tactic for distance
      runners despite few scientifically derived recommendations for individualized
      training prescription. To date, a majority of uphill training research has
      focused on shorter, faster training bouts; however, longer, slower bouts based on
      an individual's velocity at maximum oxygen consumption (Vmax) may prove more
      effective. One potential longer bout length may be associated with the time Vmax
      can be maintained (Tmax), an approach proven effective in level-grade interval
      training. Therefore, the purpose of this investigation included examining the
      Tmax, heart rate, and test-retest reliability of incline treadmill running (INC)
      on a 10% grade at 65, 70, 75, 80, and 85%Vmax compared with level-grade running
      at Vmax. Twelve moderately trained distance runners (age, 26.4 +/- 4.8; body
      mass, 64.3 +/- 12.9 kg; height, 171.2 +/- 9.3 cm; and VO2max, 56.6 +/- 7.6 ml.min
      1.kg-1) completed 2 Tmax INC trials at each submaximal Vmax and a level-grade
      Tmax at Vmax. The dependent variables were Tmax, heart rate plateau
      (HR(Plateau)), and half-time to heart rate plateau (1/2HR(Plateau)) of each
      condition. Statistical significance was set to p <= 0.05. Student's t-test
      revealed no significant differences in Tmax, HR(Plateau), and 1/2HR(Plateau)
      between trials 1 and 2 at any INC condition. One-way analysis of variance
      revealed significant differences in (a) Tmax during INC at 75, 80, and 85%Vmax
      and level-grade at Vmax and (b) 1/2HR(Plateau) during INC at 80 and 85%Vmax and
      all other conditions. In conclusion, Tmax and heart rate dynamics during INC
      proved reliable, and simple regression analysis revealed ~68%Vmax during INC
      yields the same level-grade Tmax at Vmax.

PMID- 25756324
TI  - Effects of acute and 2-hour postphysical activity on the estimation of body fat
      made by the bod pod.
AB  - The Bod Pod has been found to be reliable/valid against several criterion
      methods, including hydrostatic weighing and dual-energy x-ray absorptiometry, and
      under different conditions, such as clothing, dehydrated states, and body
      temperature changes. However, questions remain regarding the effects of an acute
      bout of exercise. Therefore, the purpose was to determine the effects of an acute
      bout of exercise on the estimations made by the Bod Pod. Participants (15 men and
      22 women) were of age 18-27 years and were currently exercising. Baseline Bod Pod
      measures were completed followed by a 30-minute cycling trial at 75% of maximum
      heart rate. Bod Pod measures were taken immediately after exercise and 2 hours
      after exercise. Differences between men and women were found at baseline between
      height (p < 0.001), weight (p < 0.001), body volume (BV; p < 0.001), and body
      density (Db; p < 0.001). Among men, body mass (p < 0.001), body fat percentage
      (%BF; p < 0.001), and BV (p < 0.001) decreased, whereas Db (p < 0.001) and body
      temperature (p < 0.001) increased directly after exercise; body mass (p < 0.001)
      and BV (p < 0.001) remained lower after 2 hours. Among women, body mass (p <
      0.001) and BV (p < 0.001) decreased, whereas thoracic gas volume (p = 0.014) and
      temperature (p < 0.001) increased directly after exercise; body mass (p < 0.001)
      and BV (p < 0.001) remained lower, whereas %BF (p < 0.001) and Db (p = 0.006)
      remained higher 2 hours after exercise. These results suggest that a single bout
      of exercise immediately before Bod Pod testing seems to alter the estimate of
      %BF, and continues to affect the prediction 2 hours after exercise in women.

PMID- 25756325
TI  - Acute Effects of Peristaltic Pneumatic Compression on Repeated Anaerobic Exercise
      Performance and Blood Lactate Clearance.
AB  - External pneumatic compression (EPC) use in athletics is increasing. However,
      there is a paucity of evidence supporting the effectiveness of EPC in aiding
      recovery and performance. We sought to determine the efficacy of EPC for acute
      recovery of anaerobic power and lactate clearance following a fatigue protocol.
      Fourteen (n = 14; women = 7 and men = 7), apparently healthy, active subjects
      (aged 22.73 +/- 4.05 years) were enrolled in this randomized crossover design
      study. After familiarization sessions, subjects completed 2 study trials
      separated by 3-7 days. Trials consisted of a fatigue protocol (two 30-second
      Wingate anaerobic tests (WAnTs) on a cycle ergometer separated by 3 minutes of
      rest), 30 minutes of treatment with EPC or sham, and, finally, a single 30-second
      WAnT. A peristaltic pulse EPC device was used with target inflation pressures of
      ~70 mm Hg applied to the lower limbs. Peak power (PkP), average power (AP), and
      the fatigue index (FI) were recorded for each WAnT. Moreover, blood lactate
      concentration (BLa) was evaluated at baseline and at regular intervals during
      recovery (5, 15, 25, and 35 minutes postfatigue protocol). No significant
      differences in PkP, AP, and FI were observed. However, BLa was significantly
      lower at 25 and 35 minutes of recovery (8.91 +/- 3.12 vs. 10.66 +/- 3.44 mmol.L(
      1) [p = 0.021] and 6.44 +/- 2.14 vs. 7.89 +/- 2.37 mmol.L(-1) [p = 0.006] for EPC
      vs. sham, respectively). Application of EPC during recovery may be a viable
      alternative when "inactive" recovery is desirable.

PMID- 25756326
TI  - Plyometric Training Effects on Athletic Performance in Youth Soccer Athletes: A
      Systematic Review.
AB  - The purpose of this systematic review was to critically analyze the literature to
      determine the effectiveness of plyometric training on athletic performance in
      youth soccer athletes. A total of 7 studies were included in this review after
      meeting the following criteria: (a) used plyometric training programs to assess
      athletic performance, (b) subjects were soccer athletes aged preadolescent up to
      17 years, and (c) were published from 2000 to January 2014. Study methods were
      assessed using the PEDro scale with scores ranging from 4 to 6. Results showed
      similarities and differences in methodologies and procedures among the included
      studies. Athletic performance consisting of kicking distance, speed, jumping
      ability, and agility significantly improved because of plyometric training
      interventions. The current evidence suggests that plyometric training should be
      completed 2 days per week for 8-10 weeks during soccer practice with a 72-hour
      rest period between plyometric training days. The initial number of foot contacts
      should be 50-60 per session and increase to no more than 80-120 foot contacts per
      session for this age group to prevent overuse injuries. A total of 3-4 plyometric
      training exercises should be performed 2-4 sets for 6-15 repetitions per training
      session. The evidence and the literature suggest that plyometric training for
      this age group should only be implemented using recommended safety guidelines
      such as those published by the Canadian Society for Exercise Physiology and the
      National Strength and Conditioning Association and under appropriate supervision
      by trained personnel.

PMID- 25756327
TI  - Elaboration of copper-oxygen mediated C-H activation chemistry in consideration
      of future fuel and feedstock generation.
AB  - To contribute solutions to current energy concerns, improvements in the
      efficiency of dioxygen mediated C-H bond cleavage chemistry, for example,
      selective oxidation of methane to methanol, could minimize losses in natural gas
      usage or produce feedstocks for fuels. Oxidative C-H activation is also a
      component of polysaccharide degradation, potentially affording alternative
      biofuels from abundant biomass. Thus, an understanding of active-site chemistry
      in copper monooxygenases, those activating strong C-H bonds is briefly reviewed.
      Then, recent advances in the synthesis-generation and study of various copper
      oxygen intermediates are highlighted. Of special interest are cupric-superoxide,
      Cu-hydroperoxo and Cu-oxy complexes. Such investigations can contribute to an
      enhanced future application of C-H oxidation or oxygenation processes using air,
      as concerning societal energy goals.

PMID- 25756328
TI  - Genetic and environmental controls on nitrous oxide accumulation in lakes.
AB  - We studied potential links between environmental factors, nitrous oxide (N2O)
      accumulation, and genetic indicators of nitrite and N2O reducing bacteria in 12
      boreal lakes. Denitrifying bacteria were investigated by quantifying genes
      encoding nitrite and N2O reductases (nirS/nirK and nosZ, respectively, including
      the two phylogenetically distinct clades nosZI and nosZII) in lake sediments.
      Summertime N2O accumulation and hypolimnetic nitrate concentrations were
      positively correlated both at the inter-lake scale and within a depth transect of
      an individual lake (Lake Vanajavesi). The variability in the individual nirS,
      nirK, nosZI, and nosZII gene abundances was high (up to tenfold) among the lakes,
      which allowed us to study the expected links between the ecosystem's nir-vs-nos
      gene inventories and N2O accumulation. Inter-lake variation in N2O accumulation
      was indeed connected to the relative abundance of nitrite versus N2O reductase
      genes, i.e. the (nirS+nirK)/nosZI gene ratio. In addition, the ratios of
      (nirS+nirK)/nosZI at the inter-lake scale and (nirS+nirK)/nosZI+II within Lake
      Vanajavesi correlated positively with nitrate availability. The results suggest
      that ambient nitrate concentration can be an important modulator of the N2O
      accumulation in lake ecosystems, either directly by increasing the overall rate
      of denitrification or indirectly by controlling the balance of nitrite versus N2O
      reductase carrying organisms. 

PMID- 25756329
TI  - Conformational dynamics of alpha-synuclein: insights from mass spectrometry.
AB  - The aggregation and deposition of alpha-synuclein in Lewy bodies is associated
      with the progression of Parkinson's disease. Here, Mass Spectrometry (MS) is used
      in combination with Ion Mobility (IM), chemical crosslinking and Electron Capture
      Dissociation (ECD) to probe transient structural elements of alpha-synuclein and
      its oligomers. Each of these reveals different aspects of the conformational
      heterogeneity of this 14 kDa protein. IM-MS analysis indicates that this protein
      is highly disordered, presenting in positive ionisation mode with a charge state
      range of 5 <=z<= 21 for the monomer, along with a collision cross section range
      of ~1600 A(2). Chemical crosslinking applied in conjunction with IM-MS captures
      solution phase conformational families enabling comparison with those exhibited
      in the gas phase. Crosslinking IM-MS identifies 3 distinct conformational
      families, Compact (~1200 A(2)), Extended (~1500 A(2)) and Unfolded (~2350 A(2))
      which correlate with those observed in solution. ECD-Fourier Transform-Ion
      Cyclotron Resonance Mass Spectrometry (ECD-FT-ICR MS) highlights the effect of pH
      on alpha-synuclein structure, identifying the conformational flexibility of the N
      and C termini as well as providing evidence for structure in the core and at
      times the C terminus. A hypothesis is proposed for the variability displayed in
      the structural rearrangement of alpha-synuclein following changes in solution pH.
      Following a 120 h aggregation time course, we observe an increase in the ratio of
      dimer to monomer, but no gross conformational changes in either, beyond the
      significant variations that are observed day-to-day from this conformationally
      dynamic protein. 

PMID- 25756330
TI  - Serum monokine induced by gamma interferon as a novel biomarker for coronary
      artery calcification in humans.
AB  - BACKGROUND: T-cell-mediated immune responses play important roles in the
      progression of atherosclerotic disease. Studies have linked various inflammatory
      biomarkers with the burden of coronary artery calcification, but the significance
      of T-cell-specific chemokines in coronary artery calcification has not been
      confirmed. We aimed to examine the association between serum levels of the
      monokine induced by gamma interferon (MIG) and the coronary artery calcium score
      (CACS). METHODS: We enrolled 456 individuals (285 men, 66.5+/-5.8 years) who were
      registered in the Mapo-gu public health center cohort. We selected 228
      individuals with a CACS of more than 100 and 228 age-matched and sex-matched
      individuals with a CACS of less than 100. All participants underwent coronary
      computed tomography for CACS measuring. Clinical and laboratory variables
      including serum MIG levels were analyzed at the time of enrollment. RESULTS: The
      serum level of MIG was significantly higher in participants with a CACS of more
      than 100 (152.1+/-119.1 vs. 130.3+/-112.9, P=0.046). Serum MIG levels correlated
      significantly with CACS (r=0.113, P=0.016), and higher levels of MIG were
      associated with severe plaque burden (CACS>400, P=0.025). Multiple linear
      regression analysis showed that serum MIG levels were associated independently
      with CACS after controlling for confounding factors and medications (beta=0.114,
      P=0.026). CONCLUSION: Serum MIG levels were associated independently with CACS
      after adjusting for traditional cardiovascular risk factors. These findings
      suggest that MIG may be used as a novel biomarker for T-cell inflammation and
      atherosclerotic plaque burden in humans.

PMID- 25756331
TI  - The relationship between vitamin D levels and saphenous vein graft patency.
AB  - OBJECTIVE: A growing body of evidence supports an association between vitamin D
      and cardiovascular diseases. Coronary artery bypass grafting surgery is a
      treatment modality for suitable patients with coronary artery disease; however,
      patency rates of saphenous vein grafts (SVGs) are low. In this study we aimed to
      determine the association between vitamin D levels and the SVG disease. METHODS:
      The study population included 180 patients who had undergone a primary coronary
      artery bypass grafting surgery with at least one SVG and later had a control
      angiography because of clinical indications. Patients were divided into two
      groups: 100 patients with SVG disease and 80 of them with patent SVG. RESULTS:
      The mean age of 180 patients was 57.4+/-8.8 years, and 64.4% of the study
      population were men. The total number of SVGs was 364, and the mean number of
      SVGs to each patient was 2.02+/-0.61. Vitamin D levels were higher in the patent
      SVG group than in the SVG disease group (36.2+/-10.7 and 21.1+/-10.4,
      respectively; P<0.001). C-reactive protein levels were significantly higher in
      the SVG disease group (8.3 vs. 6.5 mg/dl, P=0.001). In a multivariate regression
      analysis, current smoking, diabetes mellitus, target artery diameter less than
      1.5 mm, bypass time duration, and vitamin D levels remained as independent
      factors associated with SVG disease. CONCLUSION: Lower vitamin D levels are
      associated with occlusion of SVGs in patients with coronary artery disease.

PMID- 25756332
TI  - Ligand assisted carbon dioxide activation and hydrogenation using molybdenum and
      tungsten amides.
AB  - The hepta-coordinated isomeric M(NO)Cl3(PN(H)P) complexes {M = Mo, ; W, , PN(H)P
      = (iPr2PCH2CH2)2NH, (HN atom of PN(H)P syn and anti to the NO ligand)} and the
      paramagnetic species M(NO)Cl2(PN(H)P) (M = Mo, ; W, ) could be prepared via a new
      synthetic pathway. The pseudo trigonal bipyramidal amides M(NO)(CO)(PNP) {M = Mo,
      ; W, ; [PNP](-) = [(iPr2PCH2CH2)2N](-)} were reacted with CO2 at room temperature
      with CO2 approaching the M[double bond, length as m-dash]N double bond in the
      equatorial (CO,NO,N) plane trans to the NO ligand and forming the pseudo
      octahedral cyclic carbamates M(NO)(CO)(PNP)(OCO) (M = Mo, ; W = ). DFT
      calculations revealed that the approach to form the isomer is kinetically
      determined. The amine hydrides M(NO)H(CO)(PN(H)P) {M = Mo, ; W, }, obtained by H2
      addition to , insert CO2 (2 bar) at room temperature into the M-H bond generating
      isomeric mixtures of the eta(1)-formato complexes M(NO)(CO)(PN(H)P)(eta(1)-OCHO),
      (M = Mo, ; M = W, ). Closing the stoichiometric cycles for sodium formate
      formation the isomeric mixtures were reacted with 1 equiv. of Na[N(SiMe3)2]
      regenerating . Attempts to turn the stoichiometric formate production into
      catalytic CO2 hydrogenation using in the presence of various types of sterically
      congested bases furnished yields of formate salts of up to 4%. 

PMID- 25756333
TI  - Platinated oligomers of bovine pancreatic ribonuclease: Structure and stability.
AB  - The reaction between cis-diamminedichloroplatinum(II) (CDDP), cisplatin, a common
      anticancer drug, and bovine pancreatic ribonuclease (RNase A), induces extensive
      protein aggregation, leading to the formation of one dimer, one trimer and higher
      oligomers whose yields depend on cisplatin/protein ratio. Structural and
      functional properties of the purified platinated species, together with their
      spontaneous dissociation and thermally induced denaturation, have been
      characterized. Platinated species preserve a significant, although reduced,
      ribonuclease activity. The high resistance of the dimers against dissociation and
      the different thermal unfolding profiles suggest a quaternary structure different
      from those of the well-known swapped dimers of RNase A. 

PMID- 25756334
TI  - Refractive status of Chinese with laser-treated retinopathy of prematurity.
AB  - PURPOSE: To analyze changes in myopia, astigmatism, and anisometropia after laser
      treatment of retinopathy of prematurity (ROP), including aggressive posterior
      retinopathy of prematurity (APROP), in Mainland Chinese children. METHODS: This
      was a retrospective study of children who had laser treatment for threshold or
      type 1 prethreshold ROP between January 2004 and October 2012 and age-matched
      control subjects with spontaneously regressed type 2 prethreshold ROP. One
      hundred fifteen eyes of 60 patients were included as the laser-treated group,
      which were further subdivided into APROP and non-APROP groups. Thirty-seven eyes
      of 20 patients who were diagnosed during the same period were included as the
      control group. Between 12 and 36 months postnatal age (PA) (mean [+/-SD], 22.9
      [+/-8.1] months), cycloplegic retinoscopy was performed to measure refractive
      outcomes. A general linear model was used to analyze refractive changes among
      different groups at each PA. RESULTS: After adjusting for PA and the correlation
      between right and left eyes, the magnitude and proportion of astigmatism (p =
      0.04 and p = 0.004, respectively) and myopia (p < 0.0001 and p = 0.006,
      respectively) were greater in the laser-treated group than in the control group.
      The differences in myopia were even greater in children with APROP than those
      with non-APROP, whereas the differences in astigmatism were not. Eyes with APROP
      had higher prevalence of high myopia and spherical anisometropia than the control
      (p = 0.002 and p = 0.02, respectively) and the non-APROP groups (p < 0.0001 and p
      = 0.04, respectively). CONCLUSIONS: Children with laser treatment for ROP,
      including APROP, tended to have higher myopia, astigmatism, and anisometropia,
      which may progress to amblyopia. These findings highlight the need for regular
      refractive screening after laser treatment of ROP.

PMID- 25756335
TI  - Risk Factors for Dry Eye Syndrome: A Retrospective Case-Control Study.
AB  - PURPOSE: To investigate the independent risk factors of dry eye syndrome (DES) in
      Chinese. METHODS: A hospital-based age- and sex-matched population was enrolled
      with a case-control ratio of 1:2, with 789 DES case patients and 1119 healthy
      family members. Both groups underwent standard ophthalmologic examinations,
      including slit-lamp evaluation of the anterior segment, measurement of tear film
      breakup time, Schirmer test, and corneal fluorescein staining. Data on
      demographic characteristics and lifestyle habits were collected using a
      questionnaire. Dry eye syndrome risk factors were identified by univariate and
      multivariate logistic regression analyses. RESULTS: The following independent
      risk factors showed significant association with DES: diabetes (odds ratio [OR],
      1.408; 95% confidence interval [CI], 1.031 to 1.924), hepatitis C (OR, 3.326; 95%
      CI, 1.632 to 6.776); connective tissue disease (OR, 2.157; 95% CI, 1.679 to
      2.771), benign prostatic hyperplasia (OR, 3.892; 95% CI, 2.476 to 6.116), rosacea
      (OR, 3.747; 95% CI, 1.972 to 7.120), posttraumatic stress disorder (OR, 1.449;
      95% CI, 1.043 to 2.013), hematopoietic stem cell transplantation (OR, 7.269; 95%
      CI, 2.312 to 22.849), head and neck radiotherapy (OR, 8.776; 95% CI, 3.096 to
      24.873), postmenopausal estrogen therapy (OR, 1.912; 95% CI, 1.160 to 3.151),
      antihistamines (OR, 2.040; 95% CI, 1.516 to 2.746), antidepressants (OR, 1.982;
      95% CI, 1.077 to 3.647), contact lenses (OR, 2.366; 95% CI, 1.266 to 4.423), and
      video display terminal exposure for more than 6 h/d (OR, 2.275; 95% CI, 1.451 to
      3.568). Potentially protective factors against DES were vitamin supplements (OR,
      0.716; 95% CI, 0.528 to 0.972) and Omega-3 fatty acid-rich diet (OR, 0.514; 95%
      CI, 0.332 to 0.796). CONCLUSION: Several known risk factors of DES are applicable
      to Chinese, and some distinctive dietary factors may be protective in this
      population.

PMID- 25756336
TI  - Clinical presentation of pseudo-abducens palsy.
AB  - PURPOSE: Pseudo-abducens palsy is a neurologic limitation in abduction with an
      intact abducens nerve. This rare condition can be observed when voluntary eye
      movements show impairment in lateral gaze, yet the vestibulo-ocular reflex (VOR)
      demonstrates full abduction. The intact VOR indicates the integrity of the
      infranuclear abducens nerve, thus suggesting that a pseudo-abducens palsy is
      likely caused by supranuclear pathology. CASE REPORT: A 63-year-old African
      American man presented with sudden-onset, binocular, horizontal diplopia.
      Extraocular motilities revealed a complete restriction of abduction OS on
      pursuits with intermittent spasm of the right medial rectus that was most evident
      in primary and left gazes. No cyclodeviation or vertical deviation was found.
      Doll's head maneuver was used to stimulate the VOR, which facilitated complete
      abduction OS, despite its gross limitation on pursuits. The intact VOR and
      impaired abduction on pursuits, coupled with contralateral esotropia, yielded a
      diagnosis of pseudo-abducens palsy. CONCLUSIONS: Although considered to be a rare
      condition, it is important for the clinician to differentiate pseudo-abducens
      palsy from a classic abducens infranuclear palsy. Presented is a case displaying
      the typical features of a pseudo-abducens palsy, in conjunction with
      contralateral esotropia, which further supports the theory of a dysfunctional
      supranuclear vergence pathway.

PMID- 25756337
TI  - Raeder paratrigeminal neuralgia evolving to hemicrania continua.
AB  - PURPOSE: Raeder paratrigeminal neuralgia is most commonly characterized as deep,
      boring, nonpulsatile, severe, unilateral facial and head pain in the distribution
      of the V1 area combined with ipsilateral oculosympathetic palsy and autonomic
      symptoms. Raeder paratrigeminal neuralgia evolving into hemicrania continua, a
      rare primary, chronic headache syndrome characterized by unilateral pain and
      response to indomethacin, has rarely been documented. The purpose of this case
      report is to contribute to the medical literature a single case of Raeder
      paratrigeminal neuralgia presenting as multiple cranial nerve palsies that
      evolved into hemicrania continua that was successfully treated with
      onabotulinumtoxinA. CASE REPORT: A 52-year-old white woman presented to the
      emergency department with the complaint of severe, aching, constant eye pain
      radiating to the V1 area for 1 week with associated ptosis and photophobia of the
      left eye. Ocular examination revealed involvement of cranial nerves II, III, V,
      and VI. Additional symptoms included ipsilateral lacrimation, eyelid edema, and
      rhinorrhea. Extensive medical work-up showed normal results. Raeder
      paratrigeminal neuralgia was diagnosed with multiple cranial nerve involvement;
      the headache component became chronic with periodic exacerbations of autonomic
      symptoms evolving to a diagnosis of hemicrania continua. The patient was
      intolerant to traditional indomethacin treatment, and the headache was
      successfully treated with onabotulinumtoxinA injections. CONCLUSIONS: Recognition
      of ipsilateral signs such as miosis, ptosis, hydrosis, eyelid edema, hyperemia,
      rhinorrhea, or nasal congestion is useful in the differential diagnosis of
      painful ophthalmoplegia, particularly in the diagnosis of Raeder paratrigeminal
      neuralgia and hemicrania continua. This case study illustrates a rare
      presentation of Raeder paratrigeminal neuralgia evolving into hemicrania continua
      presenting as a painful ophthalmoplegia with multiple cranial nerve involvement.
      The example supports the use of oral prednisone and onabotulinumtoxinA injections
      although further study is warranted.

PMID- 25756338
TI  - Various SD-OCT features of focal choroidal excavations.
AB  - PURPOSE: To describe the clinical and spectral domain optical coherence
      tomography (OCT) features of two cases of focal choroidal excavation (FCE) and to
      review relevant literature to increase awareness and understanding of this rare
      condition. CASE REPORT: Spectral domain OCT, enhanced depth imaging, and fundus
      autofluorescence (short wavelength and near infrared) were used to study two
      cases of FCE. Both patients were asymptomatic and maintained good vision at 6
      months follow-up despite one case showing progression from a conforming- to a
      nonconforming-type FCE. At both lesion sites, the sclerochoroidal junction was
      unaltered, and the overlying retinal layers (retinal nerve fiber layer to outer
      plexiform layer) also remained intact. Enhanced depth imaging revealed an absence
      or compression of outer choroidal layers beneath the excavation and the presence
      of abnormally large choroidal vessels adjacent to the excavation. The near
      infrared autofluorescence showed improved ability to highlight the FCE lesion
      compared with traditional short-wavelength autofluorescence. CONCLUSIONS: Focal
      choroidal excavation is a rare, often asymptomatic macular condition. It appears
      on funduscopic examination as retinal pigment epithelial abnormalities, but its
      true structure is revealed with OCT. Certain spectral domain OCT imaging
      modalities, such as enhanced depth imaging and short and near-infrared
      autofluorescence, are helpful to monitor these lesions and to better understand
      its pathophysiology as it relates to choroidal vascular abnormalities.

PMID- 25756339
TI  - Simple hamartoma of the retinal pigment epithelium with macular edema.
AB  - PURPOSE: Presumed congenital simple hamartoma of the retinal pigment epithelium
      (CSHRPE) is a rare intraocular finding that is described as a focal, nodular, jet
      black lesion. These lesions frequently occur at or near the macula and have no
      known association with changes in the surrounding neurosensory retina, retinal
      pigment epithelium, or choroid, nor have they been related with exudation or
      hemorrhage. Until now, there have been no cases reported of CSHRPE with
      associated vascular activity. CASE REPORT: A 14-year-old Hispanic adolescent girl
      with a presumed CSHRPE presented with adjacent macular edema. The patient was
      treated with an off-label intravitreal bevacizumab injection to decrease the
      edema. Two months later, the patient presented with improved visual acuity and
      decreased macular edema. CONCLUSIONS: This is the first documented case of
      macular edema secondary to vascular activity being associated with these rare
      lesions. When CSHRPE is found to have secondary vascular activity and associated
      macula edema, treatment of intravitreal bevacizumab may lead to improved visual
      and anatomical outcomes.

PMID- 25756340
TI  - Corneal limbal stem cell deficiency associated with the anticancer drug S-1.
AB  - PURPOSE: An oral antineoplastic drug, S-1, is known to be more effective with
      less toxicity and fewer gastrointestinal side effects than the conventional
      intravenous 5-fluorouracil. We report a case of limbal stem cell deficiency that
      occurred in a patient receiving chemotherapy using S-1 alone for gastric cancer.
      CASE REPORT: A 65-year-old woman with symptoms of grittiness and epiphora in both
      eyes for several months was referred to the ophthalmology clinic. She had been
      receiving S-1 orally after total gastrectomy for advanced gastric cancer. Slit
      lamp examination revealed an irregular hazy corneal epithelium in both eyes that
      extended to the center of the cornea overlying the pupil and showed late staining
      with fluorescein dye. Palisades of Vogt at the superior limbus were absent in
      both eyes. Best-corrected distance vision was 20/50 in both eyes with all other
      structures of the anterior and posterior segment unremarkable including a patent
      lacrimal drainage system. There was no change in the corneal lesions of either
      eye despite 3 months of topical therapy. The lesions did resolve in 4 months
      after discontinuation of S-1 therapy owing to acute renal failure. CONCLUSIONS:
      Early detection of this adverse reaction before significant visual loss through
      regular follow-up appears to be important in patients receiving S-1 therapy.

PMID- 25756341
TI  - Aqueous humor ferritin in hereditary hyperferritinemia cataract syndrome.
AB  - PURPOSE: Hereditary hyperferritinemia cataract syndrome (HHCS) is a rare
      autosomal dominant hereditary disease, characterized by hyperferritinemia but
      with absence of body iron excess and early onset of bilateral cataracts. Although
      5- to 20-fold increased serum ferritin concentrations have been reported in HHCS
      patients, data of ferritin levels in aqueous humor have not been obtained. We
      therefore aimed to investigate the ferritin levels in aqueous humor and serum and
      further present histological and ultrastructural data of the lens. METHODS:
      During cataract extraction and intraocular lens implantation, aqueous humor and
      lens aspirate of a 37-year-old HHCS patient were obtained from both eyes.
      Ferritin levels in serum and aqueous humor were quantitatively analyzed via
      immunoassays in the HHCS patient and healthy control subjects (n = 6). Lens
      aspirate in HHCS was analyzed histologically and at the ultrastructural level.
      Further, genetic mutation screening by polymerase chain reaction and DNA
      sequencing in blood was performed. RESULTS: Serum ferritin levels in the control
      group were 142.2 +/- 38.7 MUg/L, whereas in the HHCS patient, this parameter was
      excessively increased (1086 MUg/L). Analysis of ferritin in aqueous humor
      revealed 6.4 +/- 3.8 MUg/L in normal control subjects and 146.3 MUg/L (OD) and
      160.4 MUg/L (OS) in the HHCS patient. DNA analysis detected a C>A mutation on
      position +18, a T>G mutation on position +22, a T>C mutation on position +24, and
      a T>G polymorphism on position +26 in the iron-responsive element of the light
      chain ferritin (L-ferritin) gene. CONCLUSIONS: In the HHCS patient, a 23-fold
      (OD) to 25-fold (OS) increased aqueous humor ferritin level was detected.
      Therefore, the formation of bilateral cataract in HHCS is most likely a result of
      elevated aqueous humor ferritin. In addition, a novel mutation in this rare
      disease in the iron-responsive element of L-ferritin gene is reported.

PMID- 25756342
TI  - Genetic subgroup of small ruminant lentiviruses that infects sheep homozygous for
      TMEM154 frameshift deletion mutation A4Delta53.
AB  - Small ruminant lentivirus (SRLV) infections of sheep are influenced by genetics
      on both the host and pathogen sides. Genetic variation in the ovine transmembrane
      154 (TMEM154) gene associates with infection susceptibility, and distinct SRLV
      genetic subgroups infect sheep in association with their TMEM154 diplotypes. In
      this study, a novel SRLV subgroup was identified that naturally infected sheep
      with various TMEM154 diplotypes, including those homozygous for a rare frameshift
      mutation (A4 delta53), which is predicted to abolish TMEM154 protein function.
      Thus, these SRLVs may infect sheep that lack functional TMEM154, and may not be
      restricted by TMEM154 diplotypes in establishing infections. 

PMID- 25756343
TI  - A novel way to treat skin tears.
AB  - Skin tears are one of the most commonly treated wounds in the elderly population.
      In their most basic form, they are essentially traumatic random pattern flaps. We
      postulate that the injured blood flow to these skin flaps should be ignored and
      the tissue should be treated as a skin graft. A case report is presented of an 86
      year-old female with an 8 * 3.5 cm skin tear to her right upper extremity after a
      hip fracture. In addition to conventional wound closure strips re-approximating
      the tissues, a disposable negative pressure wound therapy device was placed to
      act as bolster. Upon its removal on day 5, the opposed skin tear tissue was found
      to be 100% viable. We therefore propose that this update may be an improvement
      over classical skin tear treatments and should be followed up with a case series.

PMID- 25756344
TI  - Empirical parameters for solvent acidity, basicity, dipolarity, and
      polarizability of the ionic liquids [BMIM][BF4] and [BMIM][PF6].
AB  - The empirical solvent scales for polarizability (SP), dipolarity (SdP), acidity
      (SA), and basicity (SB) have been successfully used to interpret the
      solvatochromism of compounds dissolved in organic solvents and their solvent
      mixtures. Providing that the published solvatochromic parameters for the ionic
      liquids 1-(1-butyl)-3-methylimidazolium tetrafluoroborate, [BMIM][BF4] and 1-(1
      butyl)-3-methylimidazolium hexafluorophosphate, [BMIM][PF6], are excessively
      widespread, their SP, SdP, SA, and SB values are measured herein at temperatures
      from 293 to 353 K. Four key points are emphasized herein: (i) the origin of the
      solvatochromic solvent scales--the gas phase, that is the absence of any medium
      perturbation--; (ii) the separation of the polarizability and dipolarity effects;
      (iii) the simplification of the probing process in order to obtain the
      solvatochromic parameters; and (iv) the SP, SdP, SA, and SB solvent scales can
      probe the polarizability, dipolarity, acidity, and basicity of ionic liquids as
      well as of organic solvents and water-organic solvent mixtures. From the
      multiparameter approach using the four pure solvent scales one can draw the
      conclusion that (a) the solvent influence of [BMIM][BF4] parallels that of
      formamide at 293 K, both of them miscible with water; (b) [BMIM][PF6] shows a set
      of solvatochromic parameters similar to that of chloroacetonitrile, both of them
      water insoluble; and (c) that the corresponding solvent acidity and basicity of
      the ionic liquids can be explained to a great extent from the cation species by
      comparing the empirical parameters of [BMIM](+) with those of the solvent 1
      methylimidazole. The insolubility of [BMIM][PF6] in water as compared to
      [BMIM][BF4] is tentatively connected to some extent to the larger molar volume of
      the anion [PF6](-), and to the difference in basicity of [PF6](-) and [BF4](-).

PMID- 25756345
TI  - Reflections from the president of the Special Care Dentistry Association.

PMID- 25756346
TI  - The costs and benefits of multiple mating in a mostly monandrous wasp.
AB  - The taxonomically widespread nature of polyandry remains a puzzle. Much of the
      empirical work regarding the costs and benefits of multiple mating to females
      has, for obvious reasons, relied on species that are already highly polyandrous.
      However, this makes it difficult to separate the processes that maintain the
      current level of polyandry from the processes that facilitate its expression and
      initiated its evolution. Here we consider the costs and benefits of polyandry in
      Nasonia vitripennis, a species of parasitoid wasp that is "mostly monandrous" in
      the wild, but which evolves polyandry under laboratory culture conditions. In a
      series of six experiments, we show that females gain a direct fecundity and
      longevity benefit from mating multiply with virgin males. Conversely, mating
      multiply with previously mated males actually results in a fecundity cost. Sexual
      harassment may also represent a significant cost of reproduction. Harassment was,
      however, only costly during oviposition, resulting in reduced fecundity,
      longevity, and disrupted sex allocation. Our results show that ecological
      changes, in our case associated with differences in the local mating structure in
      the laboratory can alter the costs and benefits of mating and harassment and
      potentially lead to shifts in mating patterns.

PMID- 25756347
TI  - Molecular determinants of polyubiquitin recognition by continuous ubiquitin
      binding domains of Rad18.
AB  - Rad18 is a key factor in double-strand break DNA damage response (DDR) pathways
      via its association with K63-linked polyubiquitylated chromatin proteins through
      its bipartite ubiquitin-binding domains UBZ and LRM with extra residues between
      them. Rad18 binds K63-linked polyubiquitin chains as well as K48-linked ones and
      monoubiquitin. However, the detailed molecular basis of polyubiquitin recognition
      by UBZ and LRM remains unclear. Here, we examined the interaction of Rad18(201
      240), including UBZ and LRM, with linear polyubiquitin chains that are
      structurally similar to the K63-linked ones. Rad18(201-240) binds linear
      polyubiquitin chains (Ub2-Ub4) with affinity similar to that of a K63-linked one
      for diubiquitin. Ab initio modeling suggests that LRM and the extra residues at
      the C-terminus of UBZ (residues 227-237) likely form a continuous helix, termed
      the "extended LR motif" (ELRM). We obtained a molecular envelope for Rad18 UBZ
      ELRM:linear Ub2 by small-angle X-ray scattering and derived a structural model
      for the complex. The Rad18:linear Ub2 model indicates that ELRM enhances the
      binding of Rad18 with linear polyubiquitin by contacting the proximal ubiquitin
      moiety. Consistent with the structural analysis, mutational studies showed that
      residues in ELRM affect binding with linear Ub2, not monoubiquitin. In cell data
      support the idea that ELRM is crucial in the localization of Rad18 to DNA damage
      sites. Specifically, E227 seems to be the most critical in polyubiquitin binding
      and localization to nuclear foci. Finally, we reveal that the ubiquitin-binding
      domains of Rad18 bind linear Ub2 more tightly than those of RAP80, providing a
      quantitative basis for blockage of RAP80 at DSB sites. Taken together, our data
      demonstrate that Rad18(201-240) forms continuous ubiquitin-binding domains,
      comprising UBZ and ELRM, and provides a structural framework for polyubiquitin
      recognition by Rad18 in the DDR pathway at a molecular level. 

PMID- 25756348
TI  - The Prognostic Significance of Pretreatment Hematologic Parameters in Patients
      Undergoing Resection for Colorectal Cancer.
AB  - OBJECTIVES: The prognostic value of several hematologic parameters, including
      platelet, lymphocyte, and neutrophil counts, has been studied in a variety of
      solid tumors. In this study, we examined the significance of inflammatory markers
      and their prognostic implications in patients with colorectal cancer (CRC).
      MATERIALS AND METHODS: Patients with stage I-III CRC who underwent surgical
      resection at the Stanford Cancer Institute between 2005 and 2009 were included.
      Patients were excluded if they did not have preoperative complete blood counts
      performed within 1 month of surgical resection, underwent preoperative
      chemotherapy or radiation, had metastatic disease at diagnosis, or had another
      previous malignancy. We included 129 eligible patients with available
      preoperative complete blood counts in the final analysis. RESULTS: A preoperative
      neutrophil-to-lymphocyte ratio of>3.3 was significantly associated with worse
      disease-free (DFS) and overall survival (OS) (P=0.009, 0.003), as was a
      preoperative lymphocyte-to-monocyte ratio of <=2.6 (P=0.01, 0.002). Preoperative
      lymphopenia (P=0.002) was associated with worse OS but not DFS (P=0.09). In
      addition, preoperative thrombocytosis was associated with worse DFS (P=0.006) and
      OS (P=0.010). Preoperative leukocytosis was associated with worse OS (P=0.048)
      but not DFS (P=0.49). Preoperative hemoglobin was neither associated with OS
      (P=0.24) or DFS (P=0.15). CONCLUSIONS: Pretreatment lymphopenia, thrombocytosis,
      a decreased lymphocyte-to-monocyte ratio, and an elevated neutrophil-to
      lymphocyte ratio independently predict for worse OS in patients with CRC.

PMID- 25756349
TI  - Development of a medication monitoring attitude measure using a mixed methods
      item development process.
AB  - OBJECTIVES: Medication monitoring is important for safe and effective medication
      use; however, no attitudinal measure exists for a health care provider's
      medication monitoring attitude. The objectives of this study were to (1) create a
      measure of a community pharmacist medication monitoring attitude; (2) test
      concurrent validity using a validated measure of medication monitoring
      behaviours; and (3) report community pharmacist attitudes towards medication
      monitoring. METHODS: A mixed methods item development process was employed to
      generate Likert-type items from qualitative interviews. Following item review and
      piloting, a four-contact survey, including 20 6-point Likert-type items and the
      four-item Behavioral Pharmaceutical Care Scale monitoring domain, was mailed to
      599 randomly sampled US community pharmacists from the state of Iowa. Exploratory
      factor analysis, Pearson's correlation and descriptive statistics were used to
      address study objectives. KEY FINDINGS: There were 254 (42.4%) returned and
      usable surveys. Factor analysis yielded two domains, a seven-item, positively
      worded internal (alpha = 0.819) and an eight-item, negatively worded external
      domain (alpha = 0.811). Both domains were positively correlated with the
      monitoring domain of the Behavioral Pharmaceutical Care Scale supporting
      convergent validity. Overall, respondents had a positive internal monitoring
      attitude with a mean of 4.62 (0.68), although many practiced in an environment
      less conducive to monitoring, as evident by a mean of 3.13 (0.88). Pharmacists
      were more oriented towards medication side effect and effectiveness monitoring
      than nonadherence monitoring. CONCLUSIONS: The mixed methods item development
      process created a reliable and valid measure of a pharmacist's medication
      monitoring attitude. While pharmacists had an overall positive medication
      monitoring attitude, improvements are needed to bolster adherence monitoring and
      make pharmacy environments more conducive to monitoring.

PMID- 25756350
TI  - Correction: Chronic exercise increases plasma brain-derived neurotrophic factor
      levels, pancreatic islet size, and insulin tolerance in a TrkB-dependent manner.

PMID- 25756352
TI  - Safranal of Crocus sativus L. inhibits inducible nitric oxide synthase and
      attenuates asthma in a mouse model of asthma.
AB  - The present study involves evaluation of antioxidant potential of Crocus sativus
      and its main constituents, safranal (SFN) and crocin (CRO), in bronchial
      epithelial cells, followed antiinflammatory potential of the active constituent
      safranal, in a murine model of asthma. To investigate the antioxidizing potential
      of Crocus sativus and its main constituents in bronchial epithelial cells, the
      stress was induced in these cells by a combination of different cytokines that
      resulted in an increase in nitric oxide production (NO), induced nitric oxide
      synthase (iNOS) levels, peroxynitrite ion generation, and cytochrome c release.
      Treatment with saffron and its constituents safranal and crocin resulted in a
      decrease of NO, iNOS levels, peroxynitrite ion generation, and prevented
      cytochrome c release. However, safranal significantly reduced oxidative stress in
      bronchial epithelial cells via iNOS reduction besides preventing apoptosis in
      these cells. In the murine model of asthma study, antiinflammatory role of
      safranal was characterized by increased airway hyper-responsiveness, airway
      cellular infiltration, and epithelial cell injury. Safranal pretreatment to these
      allergically inflamed mice lead to a significant decrease in airway hyper
      responsiveness and airway cellular infiltration to the lungs. It also reduced
      iNOS production, bronchial epithelial cell apoptosis, and Th2 type cytokine
      production in the lungs.

PMID- 25756351
TI  - Perioperative neutrophil:lymphocyte ratio and postoperative NSAID use as
      predictors of survival after lung cancer surgery: a retrospective study.
AB  - The association between neutrophil:lymphocyte ratio (NLR) and poor long-term
      outcomes in patients with non-small-cell lung cancer (NSCLC) has been
      demonstrated in numerous studies. The benefit of perioperative administration of
      anti-inflammatory drugs on these outcomes has not been well established. Our aim
      in this retrospective study was to investigate the effects of postoperative
      nonsteroidal anti-inflammatory drug (NSAID) administration and NLR on tumor
      recurrence and survival in patients' undergoing surgical resection for NSCLC.
      This retrospective study included perioperative data from 1139 patients who
      underwent surgical resection for stages I-III NSCLC. Perioperative data such as
      baseline characteristics, adjuvant or neoadjuvant therapy, pre- and postoperative
      NLR, and NSAID use (ketorolac, ibuprofen, celecoxib, or in combination) were
      included. We evaluated the association between preoperative NLR and NSAID use on
      recurrence-free (RFS) and overall survival (OS). In all, 563 patients received an
      NSAID as a part of their postoperative management. The majority of patients
      received ketorolac (n = 374, 67.16%). Ketorolac administration was marginally
      associated with better OS (P = 0.05) but not with RFS (P = 0.38). Multivariate
      analysis (n = 1139) showed that preoperative NLR >5 was associated with a
      reduction in RFS (hazard ratio [HR] = 1.37; 95% confidence interval [CI] = 1.05
      1.78; P = 0.02) and OS (HR = 1.69; 95% CI = 1.27-2.23; P = 0.0003). However,
      after accounting for tumor stage, NLR >= 5 was a predictor of RFS and OS only in
      patients with stage I NSCLC. To conclude, preoperative NLR was demonstrated to be
      an independent predictor of RFS and OS in a subset of patients with early stage
      NSCLC. Ketorolac administration was not found to be an independent predictor of
      survival.

PMID- 25756353
TI  - Is Alcohol Use Disorder Identification Test (AUDIT) or its shorter versions more
      useful to identify risky drinkers in a Chinese population? A diagnostic study.
AB  - OBJECTIVE: To examine the diagnostic performance of shorter versions of Alcohol
      Use Disorder Identification Test (AUDIT), including Alcohol Consumption (AUDIT
      C), in identifying risky drinkers in primary care settings using conventional
      performance measures, supplemented by decision curve analysis and
      reclassification table. STUDY DESIGN AND SETTING: A cross-sectional study of
      adult males in general outpatient clinics in Hong Kong. The study included only
      patients who reported at least sometimes drinking alcoholic beverages. Timeline
      follow back alcohol consumption assessment method was used as the reference
      standard. A Chinese translated and validated 10-item AUDIT (Ch-AUDIT) was used as
      a screening tool of risky drinking. RESULTS: Of the participants, 21.7% were
      classified as risky drinkers. AUDIT-C has the best overall performance among the
      shorter versions of Ch-AUDIT. The AUC of AUDIT-C was comparable to Ch-AUDIT
      (0.898 vs 0.901, p-value = 0.959). Decision curve analysis revealed that when the
      threshold probability ranged from 15-30%, the AUDIT-C had a higher net-benefit
      than all other screens. AUDIT-C improved the reclassification of risky drinking
      when compared to Ch-AUDIT (net reclassification improvement = 0.167). The optimal
      cut-off of AUDIT-C was at >=5. CONCLUSION: Given the rising levels of alcohol
      consumption in the Chinese regions, this Chinese translated 3-item instrument
      provides convenient and time-efficient risky drinking screening and may become an
      increasingly useful tool.

PMID- 25756354
TI  - The excitatory synaptic transmission of the nucleus of solitary tract was
      potentiated by chronic myocardial infarction in rats.
AB  - Angina pectoris is a common clinical symptom that often results from myocardial
      infarction. One typical characteristic of angina pectoris is that the pain does
      not match the severity of the myocardial ischemia. One possible explanation is
      that the intensity of cardiac nociceptive information could be dynamically
      regulated by certain brain areas. As an important nucleus for processing cardiac
      nociception, the nucleus of the solitary tract (NTS) has been studied to some
      extent. However, until now, the morphological and functional involvement of the
      NTS in chronic myocardial infarction (CMI) has remained unknown. In the present
      study, by exploring left anterior descending coronary artery ligation surgery, we
      found that the number of synaptophysin-immunoreactive puncta and Fos
      immunoreactive neurons in the rat NTS two weeks after ligation surgery increased
      significantly. Excitatory pre- and postsynaptic transmission was potentiated. A
      bath application of a Ca2+ channel inhibitor GABApentin and Ca2+ permeable AMPA
      receptor antagonist NASPM could reverse the potentiated pre- and postsynaptic
      transmission, respectively. Meanwhile, rats with CMI showed significantly
      increased visceral pain behaviors. Microinjection of GABApentin or NASPM into the
      NTS decreased the CMI-induced visceral pain behaviors. In sum, our results
      suggest that the NTS is an important area for the process of cardiac afference in
      chronic myocardial infarction condition. 

PMID- 25756356
TI  - Right atrial and right ventricular ultrasound-guided biopsy technique in standing
      horses.
AB  - REASONS FOR PERFORMING STUDY: Endomyocardial biopsies could be a valuable tool in
      equine cardiology for diagnosing myocardial disease, which is probably
      underdiagnosed in horses because of lack of specific diagnostic measures and
      limitations of currently available diagnostic methods. OBJECTIVES: To describe a
      technique for serial right atrial and right ventricular endomyocardial biopsy in
      standing horses using a percutaneous approach through the jugular vein. STUDY
      DESIGN: Prospective study. METHODS: Biopsy was performed in 10 healthy standing
      horses sedated with detomidine, under continuous electrocardiography monitoring.
      A 10 cm (n = 6), 45 cm (n = 1) or 98 cm (n = 3) introducer sheath was inserted
      into the right jugular vein. Under echocardiographic guidance, a biopsy forceps
      was introduced through the sheath into the right ventricle and right atrium and
      endomyocardial biopsies were acquired. RESULTS: In all horses, 3 right
      ventricular biopsies were obtained from the right ventricular apex and 3 right
      atrial biopsies were obtained from the dorsal right atrial wall near the
      tuberculum intervenosum. The presence of myocardial tissue was confirmed by
      histology. All horses showed atrial and ventricular premature depolarisations
      associated with acquisition of the biopsies. In 9 horses, the arrhythmia
      disappeared after retraction of the forceps and introducer sheath. In one horse,
      ventricular premature depolarisations disappeared only after 8 h. No other
      complications were observed. CONCLUSIONS: Endomyocardial biopsy of the right
      atrium and right ventricle could be performed in standing horses using a
      percutaneous approach through the jugular vein and was not associated with
      complications other than temporary arrhythmias. This technique may be useful for
      research purposes or as a diagnostic tool, although further research is needed to
      establish the safety of the technique in clinical patients with myocardial
      disease.

PMID- 25756355
TI  - Metabolic engineering of oilseed crops to produce high levels of novel acetyl
      glyceride oils with reduced viscosity, freezing point and calorific value.
AB  - Seed oils have proved recalcitrant to modification for the production of
      industrially useful lipids. Here, we demonstrate the successful metabolic
      engineering and subsequent field production of an oilseed crop with the highest
      accumulation of unusual oil achieved so far in transgenic plants. Previously,
      expression of the Euonymus alatus diacylglycerol acetyltransferase (EaDAcT) gene
      in wild-type Arabidopsis seeds resulted in the accumulation of 45 mol% of unusual
      3-acetyl-1,2-diacyl-sn-glycerols (acetyl-TAGs) in the seed oil (Durrett et al.,
      2010 PNAS 107:9464). Expression of EaDAcT in dgat1 mutants compromised in their
      ability to synthesize regular triacylglycerols increased acetyl-TAGs to 65 mol%.
      Camelina and soybean transformed with the EaDAcT gene accumulate acetyl
      triacylglycerols (acetyl-TAGs) at up to 70 mol% of seed oil. A similar strategy
      of coexpression of EaDAcT together with RNAi suppression of DGAT1 increased
      acetyl-TAG levels to up to 85 mol% in field-grown transgenic Camelina.
      Additionally, total moles of triacylglycerol (TAG) per seed increased 20%.
      Analysis of the acetyl-TAG fraction revealed a twofold reduction in very long
      chain fatty acids (VLCFA), consistent with their displacement from the sn-3
      position by acetate. Seed germination remained high, and seedlings were able to
      metabolize the stored acetyl-TAGs as rapidly as regular triacylglycerols.
      Viscosity, freezing point and caloric content of the Camelina acetyl-TAG oils
      were reduced, enabling use of this oil in several nonfood and food applications. 

PMID- 25756358
TI  - Risk factors for unplanned hospital re-admissions: a secondary data analysis of
      hospital discharge summaries.
AB  - RATIONALE, AIMS AND OBJECTIVES: To identify patient groups at risk for unplanned
      hospital re-admissions and risk factors for re-admission. METHOD: We analysed the
      Belgian Hospital Discharge Dataset including data from 1 130 491 patients
      discharged in 2008. Patient and hospital factors contributing to re-admission
      rate were analysed using a multivariable model for logistic regression. RESULTS:
      The overall unplanned re-admission rate was 5.2%. Cardiovascular and pulmonary
      diagnoses were the most common reasons for re-admission. We found that 10.4% of
      all re-admissions were due to complications. A high number of previous emergency
      department (ED) visits proved to be a predictor for re-admission [odds ratio (OR)
      for patients with at least four ED visits in the past 6 months 4.65; 95%
      confidence interval (CI) 4.25-5.08]. Patients discharged on Friday (OR 1.05; 95%
      CI 1.01-1.08) and patients with a long length of stay (OR 1.19; 95% CI 1.15-1.23)
      also had a higher risk for re-admission. Patients with short lengths of stay were
      not at risk for re-admission (OR 0.99; 95% CI 0.95-1.02). CONCLUSIONS: Actions to
      reduce re-admissions can be targeted to patient groups at risk, and should be
      aimed at the caring for chronic cardiovascular or pulmonary diseases, preventing
      complications and multiple ED visits, and ensuring continuity of care after
      discharge, especially for patients discharged on Friday.

PMID- 25756357
TI  - Impact of helminth infection during pregnancy on cognitive and motor functions of
      one-year-old children.
AB  - OBJECTIVE: To determine the effect of helminth infection during pregnancy on the
      cognitive and motor functions of one-year-old children. METHODS: Six hundred and
      thirty five singletons born to pregnant women enrolled before 29 weeks of
      gestation in a trial comparing two intermittent preventive treatments for malaria
      were assessed for cognitive and motor functions using the Mullen Scales of Early
      Learning, in the TOVI study, at twelve months of age in the district of Allada in
      Benin. Stool samples of pregnant women were collected at recruitment, second
      antenatal care (ANC) visit (at least one month after recruitment) and just before
      delivery, and were tested for helminths using the Kato-Katz technique. All
      pregnant women were administered a total of 600 mg of mebendazole (100 mg two
      times daily for 3 days) to be taken after the first ANC visit. The intake was not
      directly observed. RESULTS: Prevalence of helminth infection was 11.5%, 7.5% and
      3.0% at first ANC visit, second ANC visit and at delivery, respectively. Children
      of mothers who were infected with hookworms at the first ANC visit had 4.9 (95%
      CI: 1.3-8.6) lower mean gross motor scores compared to those whose mothers were
      not infected with hookworms at the first ANC visit, in the adjusted model.
      Helminth infection at least once during pregnancy was associated with infant
      cognitive and gross motor functions after adjusting for maternal education,
      gravidity, child sex, family possessions, and quality of the home stimulation.
      CONCLUSION: Helminth infection during pregnancy is associated with poor cognitive
      and gross motor outcomes in infants. Measures to prevent helminth infection
      during pregnancy should be reinforced.

PMID- 25756359
TI  - Relationship of exercise capacity and left ventricular dimensions in patients
      with a normal ejection fraction. An exploratory study.
AB  - OBJECTIVES: Extreme endurance exercise is known to be associated with an
      enlargement of the left ventricular (LV) chamber, whereas inactivity results in
      inverse changes. It is unknown if these dimensional relationships exist in
      patients. METHODS: We analyzed the relationship of exercise capacity and LV
      dimension in a cohort of sequential patients with a normal ejection fraction
      undergoing stress echocardiography. In a total of 137 studies the following
      questions were addressed: (a) is there a difference in LV dimensions of patients
      with an excellent exercise capacity versus patients with a poor exercise
      capacity, (b) how is LV dimension and exercise capacity affected by LV wall
      thickness and (c) how do LV dimensions of patients who are unable to walk on a
      treadmill compare to the above groups. RESULTS: Patients with a poor exercise
      capacity or who are unable to physically exercise have a 34 percent smaller LV
      cavity size when compared to patients with an excellent exercise capacity
      (p<0.001). This reduction in LV chamber size is associated with concentric LV
      hypertrophy and a reciprocal increase in resting heart rate. In addition, cardiac
      output reserve is further blunted by chronotropic incompetence and a tachycardia
      induced LV volume reduction. In conclusion the relationship of exercise capacity
      and cardiac dimensions described in extreme athletes also applies to patients.
      Our exploratory analysis suggests that patients who cannot sufficiently exercise
      have small LV cavities.

PMID- 25756360
TI  - Minimising research bottlenecks by decluttering NMR spectra.
AB  - The lack of resolving power in everyday NMR produces ambiguous data, causing
      bottlenecks, lengthening multi-step projects and increasing the likelihood of
      making mistakes. Significant impacts can be made in many fields by minimising
      these problems with the aid of pure shift techniques. 

PMID- 25756361
TI  - Friedel-crafts alkylation of acylphloroglucinols catalyzed by a fungal indole
      prenyltransferase.
AB  - Naturally occurring prenylated acylphloroglucinol derivatives are plant
      metabolites with diverse biological and pharmacological activities. Prenylation
      of acylphloroglucinols plays an important role in the formation of these
      intriguing natural products and is catalyzed in plants by membrane-bound enzymes.
      In this study, we demonstrate the prenylation of such compounds by a soluble
      fungal prenyltransferase AnaPT involved in the biosynthesis of prenylated indole
      alkaloids. The observed activities of AnaPT toward these substrates are much
      higher than that of a microsomal fraction containing an overproduced
      prenyltransferase from the plant hop. 

PMID- 25756362
TI  - Determination of magnetic anisotropy in the LnTRENSAL complexes (Ln = Tb, Dy, Er)
      by torque magnetometry.
AB  - We report here a study about the magnetic anisotropy of the LnTRENSAL complexes
      (Ln = Tb, Dy, Er) performed by using cantilever torque magnetometry and electron
      paramagnetic resonance. For all of the compounds, we extracted a set of crystal
      field parameters to obtain the energy-level splitting of the ground-state
      multiplet. 

PMID- 25756363
TI  - The effect of disease modifying therapies on brain atrophy in patients with
      relapsing-remitting multiple sclerosis: a systematic review and meta-analysis.
AB  - BACKGROUND: The aim of the present meta-analysis was to evaluate the effect of
      disease-modifying drugs (DMD) on brain atrophy in patients with relapsing
      remitting multiple sclerosis (RRMS) using available randomized-controlled trial
      (RCT) data. METHODS: We conducted a systematic review and meta-analysis according
      to PRISMA guidelines of all available RCTs of patients with RRMS that reported
      data on brain volume measurements during the study period. RESULTS: We identified
      4 eligible studies, including a total of 1819 RRMS patients (71% women, mean age
      36.5 years, mean baseline EDSS-score: 2.4). The mean percentage change in brain
      volume was found to be significantly lower in DMD versus placebo subgroup
      (standardized mean difference: -0.19; 95%CI: -0.27--0.11; p<0.001). We detected
      no evidence of heterogeneity between estimates (I2 = 30%, p = 0.19) nor
      publication bias in the Funnel plots. Sensitivity analyses stratifying studies
      according to brain atrophy neuroimaging protocol disclosed no evidence of
      heterogeneity (p = 0.16). In meta-regression analyses, the percentage change in
      brain volume was found to be inversely related with duration of observation
      period in both DMD (meta-regression slope = -0.03; 95% CI: -0.04--0.02; p<0.001)
      and placebo subgroups (meta-regression slope = -0.05; 95% CI: -0.06--0.04;
      p<0.001). However, the rate of percentage brain volume loss over time was greater
      in placebo than in DMD subgroup (p = 0.017, ANCOVA). CONCLUSIONS: DMD appear to
      be effective in attenuating brain atrophy in comparison to placebo and their
      benefit in delaying the rate of brain volume loss increases linearly with longer
      treatment duration.

PMID- 25756364
TI  - Alcohol use among adolescent youth: the role of friendship networks and family
      factors in multiple school studies.
AB  - To explore the co-evolution of friendship tie choice and alcohol use behavior
      among 1,284 adolescents from 12 small schools and 976 adolescents from one big
      school sampled in the National Longitudinal Study of Adolescent to Adult Health
      (AddHealth), we apply a Stochastic Actor-Based (SAB) approach implemented in the
      R-based Simulation Investigation for Empirical Network Analysis (RSiena) package.
      Our results indicate the salience of both peer selection and peer influence
      effects for friendship tie choice and adolescent drinking behavior. Concurrently,
      the main effect models indicate that parental monitoring and the parental home
      drinking environment affected adolescent alcohol use in the small school sample,
      and that parental home drinking environment affected adolescent drinking in the
      large school sample. In the small school sample, we detect an interaction between
      the parental home drinking environment and choosing friends that drink as they
      multiplicatively affect friendship tie choice. Our findings suggest that future
      research should investigate the synergistic effects of both peer and parental
      influences for adolescent friendship tie choices and drinking behavior. And given
      the tendency of adolescents to form ties with their friends' friends, and the
      evidence of local hierarchy in these networks, popular youth who do not drink may
      be uniquely positioned and uniquely salient as the highest rank of the hierarchy
      to cause anti-drinking peer influences to diffuse down the social hierarchy to
      less popular youth. As such, future interventions should harness prosocial peer
      influences simultaneously with strategies to increase parental support and
      monitoring among parents to promote affiliation with prosocial peers. 

PMID- 25756365
TI  - Drug reaction with eosinophilia and systemic symptoms syndrome probably induced
      by a lamotrigine-ginseng drug interaction.
AB  - The likelihood of a drug reaction with lamotrigine is increased by dose
      escalation that is too rapid or drug interactions that increase the concentration
      of lamotrigine. There is a well-documented interaction between valproic acid and
      lamotrigine in which lamotrigine levels are increased, subsequently increasing
      the risk of a drug reaction with eosinophilia and systemic symptoms (DRESS)
      syndrome. This syndrome is characterized by fever, lymphadenopathy, diffuse
      maculopapular rash, multivisceral involvement, eosinophilia, and atypical
      lymphocytes and has a mortality rate of 10-40%. We describe the first case, to
      our knowledge, of DRESS syndrome that was probably induced by a drug interaction
      between lamotrigine and ginseng. A 44-year-old white man presented to the
      emergency department after experiencing a possible seizure. His medical history
      included two other lifetime events concerning for seizures at ages 14 and 29
      years old. After referral to the neurology clinic, he was diagnosed with
      generalized tonic-clonic seizure disorder, and lamotrigine was started with up
      titration according to the drug's package insert to a goal dosage of 150 mg
      twice/day. The patient had also been taking deer antler velvet and ginseng that
      he continued during his lamotrigine therapy. On day 43 of therapy, the patient
      presented to the emergency department with a pruritic rash that had started on
      his extremities and spread to his torso. He was thought to have experienced a
      drug reaction to lamotrigine, and the drug was discontinued. Thirteen days later,
      the patient was admitted from the acute care clinic for inpatient observation due
      to laboratory abnormalities in the setting of continued rash, headache, and
      myalgias. His admission laboratory results on that day were remarkable for
      leukocytosis, with a white blood cell count up to 17.6 * 10(3) /mm(3) , with a
      prominent eosinophilia of 3.04 * 10(3) /mm(3) ; his liver enzyme levels were also
      elevated, with an aspartate aminotransferase level of 191 U/L, alanine
      aminotransferase level 473 U/L, alkaline phosphatase level 465 U/L, and total
      bilirubin level 1.4 mg/dl. Use of the Drug Interaction Probability Scale
      indicated that a drug interaction between lamotrigine and ginseng was the
      probable cause (score of 5). The proposed mechanism of the interaction is ginseng
      inhibition of the uridine diphosphate glucuronosyltransferase 2B7 enzyme, similar
      to the mechanism of the interaction with valproic acid. Clinicians should be
      aware of this probable drug interaction and avoid coadministration of ginseng and
      lamotrigine or use a more conservative dose titration of lamotrigine for patients
      who are also taking ginseng. 

PMID- 25756366
TI  - Effect of AR-13324 on episcleral venous pressure in Dutch belted rabbits.
AB  - PURPOSE: AR-13324 is a potential new drug for the treatment of patients with
      glaucoma that has been shown to lower intraocular pressure (IOP) by increasing
      trabecular outflow facility and decreasing aqueous production. The present study
      tested the hypothesis that AR-13324 also lowers IOP by reducing episcleral venous
      pressure (EVP). METHODS: In Dutch Belted (DB) rabbits (n=11), arterial pressure
      (AP), IOP, carotid blood flow (BFcar), heart rate (HR), and EVP were measured
      invasively. Animals were dosed with AR-13324 (0.04%, topical, n=6) once daily for
      3 days. On day 3, the animals were anesthetized, and then, measurements were
      obtained before dosing with AR-13324 or vehicle (n=5) and for 3 h after dosing.
      The data (mean+/-standard error of the mean) were analyzed by repeated measures
      ANOVA with post hoc testing. Retrospective baseline data from prior similar
      studies in New Zealand White rabbits were also compiled. RESULTS: Baseline values
      were as follows: AP, 101+/-3 mmHg; IOP; 33+/-3 mmHg; EVP, 16+/-1 mmHg; BFcar,
      41+/-4 mL/min; and HR, 330+/-6 bpm. Three hours after AR-13324 dosing, IOP was
      reduced by 39%+/-7% (P<0.001) and EVP decreased by 35%+/-4% (P<0.05); after
      vehicle dosing, IOP was reduced by 24%+/-4% (P<0.05) and EVP increased by 25%+/
      5% (P<0.05). AP, BFcar, and HR were unchanged. CONCLUSIONS: AR-13324 produces
      statistically significant lowering of EVP in DB rabbits. In addition, the
      baseline values for AP, IOP, EVP, BFcar, and HR in the DB rabbit are higher than
      those previously reported in the New Zealand rabbit.

PMID- 25756367
TI  - Highly efficient antibacterial surface grafted with a triclosan-decorated poly(N
      hydroxyethylacrylamide) brush.
AB  - This work presented a highly efficient antibacterial Ti-surface which was grafted
      with poly(N-hydroxyethylacrylamide) (PHEAA) brush and further decorated with
      triclosan (TCS). The modified surfaces were characterized using contact angle
      measurements, X-ray photoelectron spectroscopy, and attenuated total reflectance
      Fourier transform infrared. The antibacterial performance of the modified
      surfaces was evaluated using the Streptococcus mutans and Actinomyces naeslundii
      attachment test. The Ti surface with PHEAA brush (Ti-PHEAA) was able to resist
      the adhesion of the bacteria, while the TCS-decorated Ti surface (Ti-TCS) showed
      the capability of killing the bacteria adhered on the surface. As we coupled the
      TCS to the PHEAA brush, the surface showed highly efficient antibacterial
      performance due to the combination of the resistance to the bacteria adhesion and
      its activity of killing bacteria. 

PMID- 25756368
TI  - Clinical significance of bile reflux into the pancreatic duct without
      pancreaticobiliary maljunction assessed by intraoperative cholangiography.
AB  - INTRODUCTION: Bile reflux into the pancreatic duct (BRPD) is sometimes
      demonstrated during intraoperative cholangiography (IOC) even in patients without
      pancreaticobiliary maljunction. However, the clinical significance of this
      finding in laparoscopic and open cholecystectomy is unclear. METHODS: Among 484
      patients who underwent cholecystectomy (372 laparoscopic, 112 open), patients
      whose pancreatic duct was depicted in IOC were selected. The value of pancreatic
      amylase (p-amylase) of the gallbladder bile, histological changes, and the
      immunohistochemical expression of proliferating cell nuclear antigen (PCNA) in
      the gallbladder mucosa were analyzed in patients with BRPD. The data were then
      compared to those in patients without BRPD whose gallbladder bile p-amylase was
      measured (control group, n = 20). RESULTS: The success rate of IOC was 93.6%. The
      rate of BRPD in laparoscopic and open cholecystectomy was 5.2% and 5.7%,
      respectively. The value of gallbladder bile p-amylase in patients with BRPD was
      significantly higher than in the control group (790.5 vs 14.0 IU/L, P = 0.034).
      The value of the PCNA labeling index in patients with BRPD was significantly
      higher than that of the control group (15.4% vs 4.1%, P = 0.0026). Among the 24
      patients with BRPD, pathological changes in the gallbladder mucosa were detected
      in five (two hyperplasia, three metaplasia), but there was no correlation between
      the presence of pathological change and PCNA labeling index or gallbladder bile p
      amylase. CONCLUSIONS: IOC could detect BRPD both in laparoscopic and open
      cholecystectomy at a similar rate. Patients with BRPD had high levels of
      gallbladder bile p-amylase and PCNA labeling index, findings similar to those in
      patients with pancreaticobiliary maljunction.

PMID- 25756369
TI  - Oxidative Povarov reaction via sp3 C-H oxidation of N-benzylanilines induced by
      catalytic radical cation salt: synthesis of 2,4-diarylquinoline derivatives.
AB  - Oxidative Povarov reaction of N-benzylanilines was realized under catalytic
      radical cation salt induced conditions. The mechanism studies revealed that a
      radical intermediate was involved in this catalytic oxidation. This method
      provides a new way to synthesize 2,4-diarylquinoline derivatives. 

PMID- 25756371
TI  - Urogynecologic conditions: foreword.

PMID- 25756372
TI  - Urogynecologic conditions: urinary incontinence.
AB  - Urinary incontinence (UI), the leakage of urine, is a condition that frequently
      goes untreated. There are many different types of UI, including stress and urge
      UI, and the etiology is multifactorial. Diagnosis can be made with a pertinent
      history, including use of a questionnaire; a pelvic examination; and direct
      observation. Additional testing can include physical maneuvers to elicit stress
      leakage and urodynamic studies. Treatment ranges from pelvic floor exercise to
      surgical support of the pelvic floor for stress UI and, typically, behavioral
      therapy and/or pharmacotherapy, starting with antimuscarinic drugs, for urge UI. 

PMID- 25756373
TI  - Urogynecologic conditions: interstitial cystitis/painful bladder syndrome.
AB  - Interstitial cystitis, also known as painful bladder syndrome, is a debilitating
      condition. The diagnosis is difficult and often is one of exclusion. Cystoscopy
      is the best way to confirm the diagnosis, but treatment can be initiated based on
      symptoms alone. Most patients benefit from an array of different drugs, including
      pentosan polysulfate, amitriptyline, hydroxyzine, and cimetidine. These
      treatments must be tailored for each patient. If oral drugs are ineffective,
      intravesical therapy can be attempted with dimethyl sulfoxide, heparin, or an
      anesthetic therapeutic combination containing lidocaine. Fulguration typically is
      performed if Hunner ulcers are found on cystoscopy. Hydrodistention, sacral
      neuromodulation, and intradetrusor onabotulinumtoxinA are sometimes useful. 

PMID- 25756370
TI  - Overexpression of an outer membrane protein associated with decreased
      susceptibility to carbapenems in Proteus mirabilis.
AB  - Proteus mirabilis isolates commonly have decreased susceptibility to imipenem.
      Previously, we found P. mirabilis hfq mutant was more resistant to imipenem and
      an outer membrane protein (OMP) could be involved. Therefore, we investigated the
      role of this OMP in carbapenem susceptibility. By SDS-PAGE we found this OMP
      (named ImpR) was increased in hfq mutant and LC-MS/MS revealed it to be the
      homologue of Salmonella YbfM, which is a porin for chitobiose and subject to MicM
      (a small RNA) regulation. We demonstrated that ImpR overexpression resulted in
      increased carbapenem MICs in the laboratory strain and clinical isolates.
      Chitobiose induced expression of chb (a chitobiose utilization operon). Real-time
      RT-PCR and SDS-PAGE were performed to elucidate the relationship of hfq, impR,
      chb and MicM in P. mirabilis. We found MicM RNA was decreased in hfq mutant and
      chbBC-intergenic region (chbBC-IGR) overexpression strain (chbIGRov), while impR
      mRNA was increased in hfq mutant, micM mutant and chbIGRov strain. In addition,
      mutation of hfq or micM and overexpression of chbBC-IGR increased ImpR protein
      level. Accordingly, chitobiose made wild-type have higher levels of ImpR protein
      and are more resistant to carbapenems. Hfq- and MicM-complemented strains
      restored wild-type MICs. Mutation of both impR and hfq eliminated the increase in
      carbapenem MICs observed in hfq mutant and ImpR-complementation of hfq/impR
      double mutant resulted in MICs as hfq mutant, indicating that the ImpR-dependent
      decreased carbapenem susceptibility of hfq mutant. These indicate MicM was
      antisense to impR mRNA and was negatively-regulated by chbBC-IGR. Together,
      overexpression of ImpR contributed to the decreased carbapenem susceptibility in
      P. mirabilis. 

PMID- 25756374
TI  - Urogynecologic conditions: pelvic organ prolapse.
AB  - Chronic pelvic pain is a commonly encountered condition that often is
      multifactorial. Etiologies include gynecologic, urologic, gastrointestinal, and
      neurologic conditions. Laboratory tests, imaging, and surgical intervention are
      not always helpful in identifying the etiology of pelvic pain. For appropriate
      management of this complex disease process, a detailed history and physical
      examination, and a multidisciplinary approach are needed. Pelvic pain may be
      caused by endometriosis, pelvic inflammatory disease, adenomyosis, interstitial
      cystitis/painful bladder syndrome, or other factors. Evaluation may include
      keeping a pain diary; laboratory tests, such as a pregnancy test, urinalysis, or
      tests for sexually transmitted infections; ultrasonography of abnormalities
      detected on physical examination; and laparoscopy. Specific first-line treatments
      include nonsteroidal anti-inflammatory drugs and oral contraceptives for
      endometriosis; progestins, gonadotropin-releasing hormone analogs, aromatase
      inhibitors, or hysterectomy for adenomyosis; and education, food avoidance, and
      behavioral modifications for interstitial cystitis/painful bladder syndrome.
      Surgical options include nerve transection procedures, laparoscopic uterosacral
      nerve ablation, and presacral neurectomy, although data on effectiveness are
      limited. 

PMID- 25756375
TI  - Urogynecologic conditions: chronic pelvic pain.
AB  - Immigration has brought millions of individuals into the United States over the
      past decade. The Centers for Disease Control and Prevention and the US Public
      Health Service are charged with ensuring that immigrants who enter do not pose a
      public health risk. Health examinations and immunization regimens are required
      for individuals wishing to live in the United States. Many immigrants and
      refugees are exposed to communicable diseases not routinely encountered in the
      United States These include helminthic infections, tuberculosis, malaria, and
      other infections. Zoonotic infections, such as influenza A, and novel coronavirus
      infections also are of increasing concern because of population mobility. 

PMID- 25756376
TI  - Spectrofluorometric and molecular docking studies on the binding of curcumenol
      and curcumenone to human serum albumin.
AB  - Curcumenol and curcumenone are two major constituents of the plants of
      medicinally important genus of Curcuma, and often govern the pharmacological
      effect of these plant extracts. These two compounds, isolated from C. zedoaria
      rhizomes were studied for their binding to human serum albumin (HSA) using the
      fluorescence quench titration method. Molecular docking was also performed to get
      a more detailed insight into their interaction with HSA at the binding site.
      Additions of these sesquiterpenes to HSA produced significant fluorescence
      quenching and blue shifts in the emission spectra of HSA. Analysis of the
      fluorescence data pointed toward moderate binding affinity between the ligands
      and HSA, with curcumenone showing a relatively higher binding constant (2.46 *
      105 M-1) in comparison to curcumenol (1.97 * 104 M-1). Cluster analyses revealed
      that site I is the preferred binding site for both molecules with a minimum
      binding energy of -6.77 kcal.mol-1. However, binding of these two molecules to
      site II cannot be ruled out as the binding energies were found to be -5.72 and 
      5.74 kcal.mol-1 for curcumenol and curcumenone, respectively. The interactions of
      both ligands with HSA involved hydrophobic interactions as well as hydrogen
      bonding. 

PMID- 25756378
TI  - Molecular characterization and functional analysis of three pathogenesis-related
      cytochrome P450 genes from Bursaphelenchus xylophilus (Tylenchida:
      Aphelenchoidoidea).
AB  - Bursaphelenchus xylophilus, the causal agent of pine wilt disease, causes huge
      economic losses in pine forests. The high expression of cytochrome P450 genes in
      B. xylophilus during infection in P. thunbergii indicated that these genes had a
      certain relationship with the pathogenic process of B. xylophilus. Thus, we
      attempted to identify the molecular characterization and functions of cytochrome
      P450 genes in B. xylophilus. In this study, full-length cDNA of three cytochrome
      P450 genes, BxCYP33C9, BxCYP33C4 and BxCYP33D3 were first cloned from B.
      xylophilus using 3' and 5' RACE PCR amplification. Sequence analysis showed that
      all of them contained a highly-conserved cytochrome P450 domain. The
      characteristics of the three putative proteins were analyzed with bioinformatic
      methods. RNA interference (RNAi) was used to assess the functions of BxCYP33C9,
      BxCYP33C4 and BxCYP33D3. The results revealed that these cytochrome P450 genes
      were likely to be associated with the vitality, dispersal ability, reproduction,
      pathogenicity and pesticide metabolism of B. xylophilus. This discovery confirmed
      the molecular characterization and functions of three cytochrome P450 genes from
      B. xylophilus and provided fundamental information in elucidating the molecular
      interaction mechanism between B. xylophilus and its host plant. 

PMID- 25756377
TI  - An overview of the prediction of protein DNA-binding sites.
AB  - Interactions between proteins and DNA play an important role in many essential
      biological processes such as DNA replication, transcription, splicing, and
      repair. The identification of amino acid residues involved in DNA-binding sites
      is critical for understanding the mechanism of these biological activities. In
      the last decade, numerous computational approaches have been developed to predict
      protein DNA-binding sites based on protein sequence and/or structural
      information, which play an important role in complementing experimental
      strategies. At this time, approaches can be divided into three categories:
      sequence-based DNA-binding site prediction, structure-based DNA-binding site
      prediction, and homology modeling and threading. In this article, we review
      existing research on computational methods to predict protein DNA-binding sites,
      which includes data sets, various residue sequence/structural features, machine
      learning methods for comparison and selection, evaluation methods, performance
      comparison of different tools, and future directions in protein DNA-binding site
      prediction. In particular, we detail the meta-analysis of protein DNA-binding
      sites. We also propose specific implications that are likely to result in novel
      prediction methods, increased performance, or practical applications. 

PMID- 25756379
TI  - Hologram QSAR models of a series of 6-arylquinazolin-4-amine inhibitors of a new
      Alzheimer's disease target: dual specificity tyrosine-phosphorylation-regulated
      kinase-1A enzyme.
AB  - Dual specificity tyrosine-phosphorylation-regulated kinase-1A (DYRK1A) is an
      enzyme directly involved in Alzheimer's disease, since its increased expression
      leads to beta-amyloidosis, Tau protein aggregation, and subsequent formation of
      neurofibrillary tangles. Hologram quantitative structure-activity relationship
      (HQSAR, 2D fragment-based) models were developed for a series of 6-arylquinazolin
      4-amine inhibitors (36 training, 10 test) of DYRK1A. The best HQSAR model (q2 =
      0.757; SEcv = 0.493; R2 = 0.937; SE = 0.251; R2pred = 0.659) presents high
      goodness-of-fit (R2 > 0.9), as well as high internal (q2 > 0.7) and external
      (R2pred > 0.5) predictive power. The fragments that increase and decrease the
      biological activity values were addressed using the colored atomic contribution
      maps provided by the method. The HQSAR contribution map of the best model is an
      important tool to understand the activity profiles of new derivatives and may
      provide information for further design of novel DYRK1A inhibitors. 

PMID- 25756380
TI  - Development of small RNA delivery systems for lung cancer therapy.
AB  - RNA interference (RNAi) has emerged as a powerful tool for studying target
      identification and holds promise for the development of therapeutic gene
      silencing. Recent advances in RNAi delivery and target selection provide
      remarkable opportunities for translational medical research. The induction of
      RNAi relies on small silencing RNAs, which affect specific messenger RNA (mRNA)
      degradation. Two types of small RNA molecules, small interfering RNAs (siRNAs)
      and microRNAs (miRNAs), have a central function in RNAi technology. The success
      of RNAi-based therapeutic delivery may be dependent upon uncovering a delivery
      route, sophisticated delivery carriers, and nucleic acid modifications. Lung
      cancer is still the leading cause of cancer death worldwide, for which novel
      therapeutic strategies are critically needed. Recently, we have reported a novel
      platform (PnkRNATM and nkRNA(r)) to promote naked RNAi approaches through
      inhalation without delivery vehicles in lung cancer xenograft models. We suggest
      that a new class of RNAi therapeutic agent and local drug delivery system could
      also offer a promising RNAi-based strategy for clinical applications in cancer
      therapy. In this article, we show recent strategies for an RNAi delivery system
      and suggest the possible clinical usefulness of RNAi-based therapeutics for lung
      cancer treatment. 

PMID- 25756381
TI  - Mechanistic studies on the dibenzofuran formation from phenanthrene, fluorene and
      9-fluorenone.
AB  - We carried out molecular orbital theory calculations for the homogeneous gas
      phase formation of dibenzofuran from phenanthrene, fluorene, 9-methylfluorene and
      9-fluorenone. Dibenzofuran will be formed if ?OH adds to C8a, and the order of
      reactivity follows as 9-fluorenone > 9-methylfluorene > fluorene > phenanthrene.
      The oxidations initiated by ClO? are more favorable processes, considering that
      the standard reaction Gibbs energies are at least 21.63 kcal/mol lower than those
      of the equivalent reactions initiated by ?OH. The adding of ?OH and then O2 to
      phenanthrene is a more favorable route than adding ?OH to C8a of phenanthrene,
      when considering the greater reaction extent. The reaction channel from fluorene
      and O2 to 9-fluorenone and H2O seems very important, not only because it contains
      only three elementary reactions, but because the standard reaction Gibbs energies
      are lower than -80.07 kcal/mol.

PMID- 25756384
TI  - Call for scientific submissions 2016 ACC RAC.

PMID- 25756382
TI  - Infection Prevention and Control in the Podiatric Medical Setting: Challenges to
      Providing Consistently Safe Care.
AB  - Unsafe practices are an underestimated contributor to the disease burden of
      bloodborne viruses. Outbreaks associated with failures in basic infection
      prevention have been identified in nonhospital settings with increased frequency
      in the United States during the past 15 years, representing an alarming trend and
      indicating that the challenge of providing consistently safe care is not always
      met. As has been the case with most medical specialties, there have been public
      health investigations by state and local health departments, and the Centers for
      Disease Control and Prevention have identified some instances of unsafe practices
      that have placed podiatric medical patients at risk for viral, bacterial, and
      fungal infections. All health-care providers, including podiatric physicians,
      must make infection prevention a priority in any setting in which care is
      delivered.

PMID- 25756385
TI  - Call for workshop proposals 2016 ACC RAC.

PMID- 25756386
TI  - Poster presentation abstracts.

PMID- 25756387
TI  - A comprehensive approach in diagnosing the polycystic ovary syndrome.
AB  - The polycystic ovary syndrome is the commonest hyperandrogenic and dysmetabolic
      disorder in women that, by definition, may present with different phenotypes,
      including the classic forms and those with a milder presentation. Its diagnosis
      is mainly based on careful clinical judgment, although it may require additional
      investigation by blood testing or imaging techniques in the differential
      diagnosis of androgen excess. This article summarizes the most important aspects
      of the diagnostic procedure and suggests how to apply them in clinical practice. 

PMID- 25756388
TI  - Relationships Between Propulsion and Anthropometry in Paralympic Swimmers.
AB  - PURPOSE: To characterize relationships between propulsion, anthropometry, and
      performance in Paralympic swimming. METHODS: A cross-sectional study of swimmers
      (13 male, 15 female) age 20.5 +/- 4.4 y was conducted. Subject locomotor
      categorizations were no physical disability (n = 8, classes S13-S14) and low
      severity (n = 11, classes S9-S10) or midseverity disability (n = 9, classes S6
      S8). Full anthropometric profiles estimated muscle mass and body fat, a bilateral
      swim-bench ergometer quantified upper-body power production, and 100-m time
      trials quantified swimming performance. RESULTS: Correlations between ergometer
      mean power and swimming performance increased with degree of physical disability
      (low-severity male r = .65, +/- 0.56, and female r = .68, +/- 0.64; midseverity,
      r = .87, +/- 0.41, and r = .79, +/- 0.75). The female midseverity group showed
      nearperfect (positive) relationships for taller swimmers' (with a greater muscle
      mass and longer arm span) swimming faster, while for female no- and low-severity
      disability groups, greater muscle mass was associated with slower velocity (r =
      .78, +/- 0.43, and r = .65, +/- 0.66). This was supported with lighter females
      (with less frontal surface area) in the low-severity group being faster (r = .94,
      +/- 0.24). In a gender contrast, low-severity males with less muscle mass (r = 
      .64, +/- 0.56), high skinfolds (r = .78, +/- 0.43), a longer arm span (r = .58,
      +/- 0.60) or smaller frontal surface area (r = -.93, +/- 0.19) were detrimental
      to swimming-velocity production. CONCLUSION: Low-severity male and midseverity
      female Paralympic swimmers should be encouraged to develop muscle mass and upper
      body power to enhance swimming performance. The generalized anthropometric
      measures appear to be a secondary consideration for coaches.

PMID- 25756389
TI  - An infant with a diagnostically challenging hepatic teratoma, hypofibrinogenemia,
      and adrenal neuroblastoma: case report.
AB  - Teratomas of the liver are exceedingly rare. Neuroblastoma is the most common,
      extracranial solid tumor of infancy. We describe the case of a 2-month-old,
      female infant who presented with an abdominal mass arising in the right lobe of
      the liver, and a severe coagulopathy, which necessitated cryoprecipitate
      infusion. Biopsy was interpreted as hepatoblastoma. Following resection,
      difficulty classifying the mass led to several consultations, and an eventual
      diagnosis of teratoma. During follow-up, the patient was diagnosed with right
      adrenal neuroblastoma, which, in retrospect, had been present before the hepatic
      resection. To our knowledge, these 2 tumors have never been reported together, or
      in combination with isolated hypofibrinogenemia. 

PMID- 25756390
TI  - Transition metal-free generation of N-unsubstituted imines from benzyl azides:
      synthesis of N-unsubstituted homoallylic amines.
AB  - An efficient transition metal-free approach for the generation of N-unsubstituted
      imines from azides followed by trapping with allyl nucleophile to provide N
      unsubstituted homoallylic amines has been described. Although catalytic KO(t)Bu
      in DMSO is sufficient to allow imine generation, stoichiometric KO(t)Bu is
      essential in THF. Further, an enantio- and diastereoselective synthesis of
      homoallylic amines from benzyl azide has also been exemplified. 

PMID- 25756393
TI  - Chiral recognition and selection during the self-assembly process of protein
      mimic macroanions.
AB  - The research on chiral recognition and chiral selection is not only fundamental
      in resolving the puzzle of homochirality, but also instructive in chiral
      separation and stereoselective catalysis. Here we report the chiral recognition
      and chiral selection during the self-assembly process of two enantiomeric wheel
      shaped macroanions, [Fe28(MU3-O)8(Tart)16(HCOO)24](20-) (Tart=D- or L-tartaric
      acid tetra-anion). The enantiomers are observed to remain self-sorted and self
      assemble into their individual assemblies in their racemic mixture solution. The
      addition of chiral co-anions can selectively suppress the self-assembly process
      of the enantiomeric macroanions, which is further used to separate the two
      enantiomers from their mixtures on the basis of the size difference between the
      monomers and the assemblies. We believe that delicate long-range electrostatic
      interactions could be responsible for such high-level chiral recognition and
      selection. 

PMID- 25756394
TI  - TGFbeta-induced phosphorylation of Par6 promotes migration and invasion in
      prostate cancer cells.
AB  - BACKGROUND: The Par complex - comprising partition-defective 6 (Par6), Par3, and
      atypical protein kinase C (aPKC) - is crucial for cell polarisation, the loss of
      which contributes to cancer progression. Transforming growth factor beta
      (TGFbeta)-induced phosphorylation of Par6 on the conserved serine 345 is
      implicated in epithelial-to-mesenchymal transition (EMT) in breast cancer. Here
      we investigated the importance of phosphorylated Par6 in prostate cancer.
      METHODS: We generated a p-Par6(345)-specific antibody and verified its
      specificity in vitro. Endogenous p-Par6(345) was analysed by immunoblotting in
      normal human prostate RWPE1 and prostate cancer (PC-3U) cells. Subcellular
      localisation of p-Par6(345) in migrating TGFbeta-treated PC-3U cells was analysed
      by confocal imaging. Invasion assays of TGFbeta-treated PC-3U cells were
      performed. p-Par6 expression was immunohistochemically analysed in prostate
      cancer tissues. RESULTS: TGFbeta induced Par6 phosphorylation on Ser345 and its
      recruitment to the leading edge of the membrane ruffle in migrating PC-3U cells,
      where it colocalised with aPKCzeta. The p-Par6-aPKCzeta complex is important for
      cell migration and invasion, as interference with this complex prevented prostate
      cancer cell invasion. High levels of activated Par6 correlated with aggressive
      prostate cancer. CONCLUSIONS: Increased p-Par6Ser(345) levels in aggressive
      prostate cancer tissues and cells suggest that it could be a useful novel
      biomarker for predicting prostate cancer progression.

PMID- 25756395
TI  - The effect of chemotherapy on health-related quality of life in mesothelioma:
      results from the SWAMP trial.
AB  - BACKGROUND: The effect of chemotherapy on health-related quality of life (HRQoL)
      in malignant pleural mesothelioma (MPM) is poorly understood. Patient
      individualised prognostication and prediction of treatment response from
      chemotherapy is useful but little evidence exists to guide practice. METHOD:
      Consecutive patients with MPM who were fit for first-line chemotherapy with
      pemetrexed and cisplatin?carboplatin were recruited and followed up for a minimum
      of 12 months. This study focussed on the HRQoL outcomes of these patients using
      the EQ-5D, EORTC QLQ-C30 and LC13. RESULTS: Seventy-three patients were recruited
      of which 58 received chemotherapy and 15 opted for best supportive care (BSC).
      Compliance with HRQoL questionnaires was 98% at baseline. The chemotherapy group
      maintained HRQoL compared with the BSC group whose overall HRQoL fell (P=0.006)
      with worsening dyspnoea and pain. The impact of chemotherapy was irrespective of
      histological subtype although those with non-epithelioid disease had worse HRQoL
      at later time points (P=0.012). Additionally, those with a falling mesothelin or
      improvement on modified-RECIST CT at early follow-up had a better HRQoL at 16
      weeks. CONCLUSIONS: HRQoL was maintained following chemotherapy compared with a
      self-selected BSC group. Once chemotherapy is initiated, a falling mesothelin or
      improved RECIST CT findings infer a quality-of-life advantage.

PMID- 25756396
TI  - The South West Area Mesothelioma and Pemetrexed trial: a multicentre prospective
      observational study evaluating novel markers of chemotherapy response and
      prognostication.
AB  - BACKGROUND: Robust markers that predict prognosis and detect early treatment
      response in malignant pleural mesothelioma (MPM) would enhance patient care.
      METHODS: Consecutive patients with MPM who were considered fit for first-line
      chemotherapy were prospectively recruited. Patients of similar performance status
      opting for best supportive care were included as a comparator group. Baseline and
      interval CT, PET-CT and serum markers (mesothelin, fibulin-3 and neutrophil
      lymphocyte ratio (NLR)) were obtained, and patients followed up for a minimum 12
      months. FINDINGS: Seventy-three patients were recruited (58 chemotherapy/15
      comparator arm). Baseline TGV (total glycolytic volume on PET-CT) was an
      independent predictor of worse overall survival (OS) (P=0.001). Change in
      interval TGV(baseline/after two cycles of chemotherapy) did not predict OS or
      chemotherapy response on CT. Baseline NLR<4 was an independent predictor of
      better OS (median survival 453 (IQR 272-576) days vs NLR?4, 257 (IQR 147-490),
      P=0.002). Although baseline serum mesothelin did not predict OS, a falling level
      at 8 weeks significantly predicted longer time to progression (TTP) (P<0.001).
      INTERPRETATION: Neutrophil-lymphocyte ratio and baseline TGV predict prognosis in
      malignant pleural mesothelioma (MPM), but PET-CT is unhelpful in monitoring
      chemotherapy response. Serum mesothelin is a useful early treatment response
      marker when measured serially during chemotherapy and may have a role in
      evaluating patients' treatment response.

PMID- 25756397
TI  - Serum microRNA-210 as a potential noninvasive biomarker for the diagnosis and
      prognosis of glioma.
AB  - BACKGROUND: MicroRNA-210 (miR-210) is an oncogenic miRNA previously associated
      with prognosis in human gliomas, an incurable tumour type of the central nervous
      system. Here miR-210 was investigated as a potential serum biomarker in the
      diagnosis and prognosis of glioma. METHODS: Serum was immediately prepared from
      blood samples collected from patients with glioma grades I-IV at primary
      diagnosis (n=136) and healthy controls (n=50) from February 2007 to March 2014 in
      the Department of Neurosurgery of the First Affiliated Hospital of Wannan Medical
      College (Wuhu, China). Total RNA was isolated from serum. cDNA was synthesised
      with primers specific for miR-210 and miR-16-1 (internal control), and
      quantitative real-time RT-PCR was performed. Results were statistically analysed
      to determine the role of miR-210 in the diagnosis and prognosis of human glioma
      patients. RESULTS: An approximately seven-fold increase in miR-210 expression was
      detected in serum samples from glioblastoma patients relative to healthy
      controls. A threshold expression value (2.259) was chosen from receiver operator
      characteristic curves (ROC), and the low and high miR-210 expression groups were
      analysed by multivariate Cox proportional hazard regression and Kaplan-Meier
      analyses. Results revealed an association of high serum miR-210 expression with
      tumour grade and poor patient outcome (P-values <0.001). CONCLUSIONS: Serum miR
      210 is a promising diagnostic and prognostic biomarker that can be detected in
      the peripheral blood of patients with glioma.

PMID- 25756398
TI  - Circulating cytokines and monocyte subpopulations as biomarkers of outcome and
      biological activity in sunitinib-treated patients with advanced neuroendocrine
      tumours.
AB  - BACKGROUND: Sunitinib is approved worldwide for treatment of advanced pancreatic
      neuroendocrine tumours (pNET), but no validated markers exist to predict
      response. This analysis explored biomarkers associated with sunitinib activity
      and clinical benefit in patients with pNET and carcinoid tumours in a phase II
      study. METHODS: Plasma was assessed for vascular endothelial growth factor (VEGF)
      A, soluble VEGF receptor (sVEGFR)-2, sVEGFR-3, interleukin (IL)-8 (n=105), and
      stromal cell-derived factor (SDF)-1alpha (n=28). Pre-treatment levels were
      compared between tumour types and correlated with response, progression-free
      (PFS), and overall survival (OS). Changes in circulating myelomonocytic and
      endothelial cells were also analysed. RESULTS: Stromal cell-derived factor-1alpha
      and sVEGFR-2 levels were higher in pNET than in carcinoid (P=0.003 and 0.041,
      respectively). High (above-median) baseline SDF-1alpha was associated with worse
      PFS, OS, and response in pNET, and high sVEGFR-2 with longer OS (P?0.05). For
      carcinoid, high IL-8, sVEGFR-3, and SDF-1alpha were associated with shorter PFS
      and OS, and high IL-8 and SDF-1alpha with worse response (P?0.05). Among
      circulating cell types, monocytes showed the largest on-treatment decrease,
      particularly CD14+ monocytes co-expressing VEGFR-1 or CXCR4. CONCLUSIONS:
      Interleukin-8, sVEGFR-3, and SDF-1alpha were identified as predictors of
      sunitinib clinical outcome. Putative pro-tumorigenic CXCR4+ and VEGFR-1+
      monocytes represent novel candidate markers and biologically relevant targets
      explaining the activity of sunitinib.

PMID- 25756399
TI  - Photo-oxidation of ergosterol: indirect detection of antioxidants
      photosensitizers or quenchers of singlet oxygen.
AB  - Consumption of antioxidant supplements is associated to prevention of several
      diseases. However, recent studies suggest that antioxidants, besides scavenge
      free radicals could lead development of tumors. Due to conflicting reports on the
      antioxidant benefits, the capacity to photosensitize the generation of singlet
      oxygen of seven natural antioxidants was evaluated through photo-oxidation of
      ergosterol which proved to be an efficient method of indirect detection of
      singlet oxygen. Our results showed that curcumin, resveratrol and quercetin have
      pro-oxidant activity due they act as photosensitizers in generation of singlet
      oxygen. In addition, we observed that genistein, naringenin, beta-carotene and
      gallic acid besides their antioxidant activity against ROS radicals, are capable
      of quenching ROS non-radicals as singlet oxygen. Finally, our results allow us to
      propose a new approach in classification of natural antioxidants scavengers of
      free radicals, based on their activity as quenchers of singlet oxygen or as
      photosensitizers in singlet oxygen generation. 

PMID- 25756400
TI  - Endometrial cancers in mutation carriers from hereditary breast ovarian cancer
      syndrome kindreds: report from the Creighton University Hereditary Cancer
      Registry with review of the implications.
AB  - OBJECTIVE: The aim of this study was to categorize and report endometrial cancers
      in mutation carriers from hereditary breast ovarian cancer families. METHODS: Our
      Hereditary Cancer Registry was searched for gynecologic and peritoneal cancers
      linked to mutations in BRCA1 or BRCA2. Invasive cancers were registered in 101
      mutation carriers with complete pathology reports. Efforts were made to secure
      diagnostic surgical pathology tissues for review. All records and available
      diagnostic slides were meticulously studied, and primary cancers were classified.
      FINDINGS: Eight malignancies were classified as primary endometrial cancers. Five
      of these were low- or intermediate-grade endometrioid carcinomas, and 3 were pure
      serous carcinomas or contained serous carcinoma elements mixed with high-grade
      endometrioid carcinoma. Breast cancers were diagnosed in 5 patients before and in
      1 patient after endometrial carcinoma. Three endometrioid carcinomas were
      preceded by estrogen treatment, 2 for many years and the other for only 2 months,
      and 2 of the patients with serous carcinoma had been treated with tamoxifen.
      CONCLUSIONS: The finding that 8 of gynecologic and peritoneal cancers in 101
      mutation carriers were endometrial cancers with a smaller proportion of
      endometrioid carcinomas than reported in general populations is added to the
      current controversial literature on endometrial cancer, particularly regarding
      serous carcinomas, in hereditary breast ovarian cancer syndrome. Well-designed
      prospective programs for standardized surgical and pathologic handling,
      processing, and reporting are essential for working out the pathogenesis, true
      risks, and best management of this disease in carriers of deleterious BRCA1 and
      BRCA2 germline mutations.

PMID- 25756401
TI  - An organizational guideline for gynecologic oncology services.
AB  - OBJECTIVES: Documented variations in practice compelled the need to establish a
      network that would facilitate the flow of patients through the care continuum of
      a provincial health care system in accordance with best practices. Therefore, a
      guideline was developed to provide recommendations for the optimal organization
      of gynecologic oncology services in this higher resource location to improve
      access to multidisciplinary care and appropriate treatment. METHODS: A systematic
      review was conducted of Web sites of international guideline developers, relevant
      cancer agencies, and Medline and EMBASE from 1996 to 2011 using search terms
      related to gynecologic malignancies, combined with organization of services,
      patterns of care, and various facility and physician characteristics. The results
      of the review were combined with expert consensus and stakeholder consultation to
      develop a gynecologic oncology services organizational guideline. RESULTS: The
      evidence review yielded a lower quality evidence base; therefore, recommendations
      were determined through consensus, including guidance for physician and hospital
      specialization, and other domains including human and physical resources.
      Definitive surgical treatment of most invasive cancers by subspecialist
      gynecologic oncologists is recommended. In addition, it is recommended that these
      subspecialists provide care within designated gynecologic oncology centers. The
      recommendations also outline which services, such as radiation therapy, may be
      provided in other affiliated centers. Multidisciplinary team management is also
      endorsed. CONCLUSIONS: These recommendations are intended to allow a
      collaborative community of practice, supported by formal interorganizational
      processes, to evolve to facilitate adherence to guidelines and best practices at
      a system-wide level.

PMID- 25756402
TI  - High Pretreatment Plasma D-dimer Levels Are Associated With Poor Prognosis in
      Patients With Ovarian Cancer Independently of Venous Thromboembolism and Tumor
      Extension.
AB  - OBJECTIVE: Elevated plasma D-dimer (DD) is associated with decreased survival
      among patients with breast, lung, and colon cancers. The present study clarifies
      the prognostic significance of pretreatment plasma DD levels in patients with
      epithelial ovarian cancer (EOC). METHODS: We investigated pretreatment DD levels
      and other variables for overall survival using univariate and multivariate
      analyses in 134 consecutive patients with EOC stages II to IV who were initially
      treated between November 2004 and December 2010. RESULTS: The median follow-up
      period was 53 (7-106) months. Univariate analysis significantly associated
      elevated pretreatment DD (>=2.0 MUg/mL) levels to poor 5-year overall survival
      rates irrespective of previously treated venous thromboembolism (72.2% vs 52.6%,
      P = 0.039). Cancer antigen 125 levels of 200 U/mL or higher (P = 0.011), distant
      metastases (P = 0.0004), residual tumors (P < 0.0001), and International
      Federation of Gynecology and Obstetrics stage III/IV (P = 0.0033) were also poor
      prognostic factors. Multivariate analysis independently associated DD levels of
      2.0 MUg/mL or higher (P = 0.041), distant metastases (P = 0.013), and residual
      tumors (P < 0.0001) with poor overall survival. CONCLUSIONS: High pretreatment DD
      levels are associated with poor overall survival in patients with EOC
      independently of venous thromboembolism and tumor extension and might comprise a
      promising prognostic biomarker for patients with EOC.

PMID- 25756403
TI  - Functions and Mechanisms of Long Noncoding RNAs in Ovarian Cancer.
AB  - Long noncoding RNAs (lncRNAs) are longer than 200-nucleotide, noncoding
      transcripts in length, have a variety of biological functions, and are closely
      associated with tumor development. Ovarian cancer, as 1 of the 3 common
      gynecological malignancies, is the leading cause of death in women with
      gynecological malignant tumor. In this study, a review of the literature found
      that lncRNAs H19, LSINCT5, and XIST have a close relationship to the development
      of ovarian cancer occurrence, growth, invasion, and metastasis, and they can
      promote ovarian cancer cell proliferation. Hence, in this article, the progress
      of above-mentioned 3 kinds of lncRNAs in ovarian cancer was reviewed and designed
      to help in the diagnosis, treatment, and prognosis of ovarian cancer. 

PMID- 25756404
TI  - Does omentectomy in epithelial ovarian cancer affect survival? An analysis of the
      Surveillance, Epidemiology, and End Results database.
AB  - OBJECTIVE: Although omentectomy is part of the staging and treatment of
      epithelial ovarian cancer (EOC), its performance in a patient with a grossly
      normal omentum-acknowledging its role in debulking gross tumor deposits-has never
      been definitively shown to improve survival. METHODS/MATERIALS: Using
      Surveillance, Epidemiology, and End Results data from 1998 to 2010, we identified
      patients with EOC and assessed their age, race, year of diagnosis, tumor grade,
      histologic subtype, International Federation of Gynecology and Obstetrics stage,
      lymph node dissection, nodal findings, and performance of omentectomy. We
      compared disease-specific survival (DSS) based on the presence or absence of
      omentectomy using log-rank univariate analysis, Cox multivariate analysis, and
      Kaplan-Meier survival curves. RESULTS: A total of 20,975 patients with invasive
      EOC underwent surgical treatment. Initial univariate analysis indicated a lower
      mean DSS with performance of omentectomy. However, multivariate analysis
      demonstrated no significant association between DSS and performance of
      omentectomy (hazard ratio, 0.978; P = 0.506). The DSS was improved if
      lymphadenectomy was performed (hazard ratio, 0.60; P < 0.001). In recent years,
      there was a trend toward decreased performance of omentectomy.To look
      specifically at patients without bulky omental disease, a subset analysis was
      done looking at patients with stage I-IIIA disease who had had lymphadenectomy
      performed. There were 5454 patients in the group who underwent an omentectomy and
      2404 patients in the group who did not. No difference in DSS was seen between the
      groups based on performance of omentectomy (P = 0.89). However, the analysis was
      limited by the lack of Surveillance, Epidemiology, and End Results data on the
      extent of omentectomy, amount of residual disease, and adjuvant chemotherapy.
      CONCLUSIONS: In this analysis, performance of omentectomy in patients with EOC
      without bulky disease (<=stage IIIA) did not seem to confer improvement in
      survival. A randomized control trial would be needed to fully address this
      question.

PMID- 25756405
TI  - Fibroblast growth factor receptor 2 is associated with poor overall survival in
      clear cell carcinoma of the ovary and may be a novel therapeutic approach.
AB  - OBJECTIVE: We previously found that gene and protein expression of fibroblast
      growth factor receptor (FGFR) 2 were increased in ovarian clear cell carcinoma
      (CCC); here, we examined FGFR2 expression in CCC tumor tissues and its
      correlation with clinical parameters. We also analyzed the effect of an FGFR
      inhibitor on the growth of CCC cells to investigate whether FGFR2 could be a
      therapeutic target for this disease. METHODS: We analyze the protein expression
      of FGFR2 by immunohistochemical staining in CCC from 112 patients and evaluated
      the association of these molecular parameters with clinical outcome. We treated
      the 11 CCC cell lines with an FGFR inhibitor, and then assessed cell viability,
      the expression of protein in FGFR2 signaling pathway, and cell cycle
      distribution. RESULTS: The expressions of FGFR2 were found in 96% of CCC. The 5
      year survival rate for patients with a moderate or strong expression of FGFR2 was
      significantly lower than that for those with an absent or poor expression of
      FGFR2 (54% vs 79%). Multivariable analysis revealed that FGFR2 expression and
      disease stage were independent prognostic factors. The FGFR inhibitor effectively
      suppressed the growth of CCC cells with induction of G1 cell cycle arrest and
      down-regulated the expression of phosphorylated Akt and phosphorylated ERK.
      CONCLUSIONS: FGFR2 is an important biomarker predictive of patient outcome and is
      a potential target for CCC. Further study is warranted for FGFR inhibitor to
      treat CCC.

PMID- 25756406
TI  - Chemical ligation methods for the tagging of DNA-encoded chemical libraries.
AB  - The generation of DNA-encoded chemical libraries requires the unimolecular
      association of multiple encoding oligonucleotides with encoded chemical entities
      during combinatorial synthesis processes. This has traditionally been achieved
      using enzymatic ligation. We discuss a range of chemical ligation methods that
      provide alternatives to enzymatic ligation. These chemical ligation methods
      include the generation of modified internucleotide linkages that support
      polymerase translocation and other modified linkages that while not supporting
      the translocation of polymerases can also be used to generate individual cDNA
      molecules containing encoded chemical information specifying individual library
      members. We also describe which of these approaches have been successfully
      utilized for the preparation of DNA-encoded chemical libraries and those that
      were subsequently used for the discovery of inhibitors. 

PMID- 25756408
TI  - Gene expression profiling analysis of patients with ankylosing spondylitis.
AB  - STUDY DESIGN: A comprehensive bioinformatics analysis of genes which may have
      correlations with ankylosing spondylitis (AS). OBJECTIVE: To study the mechanisms
      of AS by analyzing microarray of GSE25101. SUMMARY OF BACKGROUND DATA: AS is an
      inflammatory arthritis that can lead to chronic pain and disability. MATERIALS
      AND METHODS: GSE25101 was downloaded from Gene Expression Omnibus including 16 AS
      patients and 16 normal controls. The differentially expressed genes (DEGs) were
      screened using limma package in Bioconductor and miRNAs targeted DEGs were
      predicted. Then, gene ontology and pathway enrichment analysis of DEGs was
      performed using Database for Annotation, Visualization, and Integrated Discovery.
      Besides, the interaction relationships of the proteins encoded by DEGs were
      searched by STRING, and the protein-protein interaction (PPI) network was
      visualized by Cytoscape. Moreover, modules analysis of PPI network was performed
      using Clique Percolation Method in CFinder. RESULTS: A total of 284 DEGs were
      screened and 1899 miRNA-mRNA regulatory pairs were obtained. Both myosin heavy
      chain 9 (MYH9) and B-cell chronic lymphocytic leukemia/lymphoma 11B (BCL11B) were
      targeted by has-miR-124 and has-miR-363. Function enrichment analyze indicated
      that these DEGs, especially, downregulated protein tyrosine phosphatase receptor
      type C (PTPRC), cluster of differentiation 3gamma (CD3G), cluster of
      differentiation 247 (CD247), cluster of differentiation 4 (CD4), interleukin 7
      receptor (IL7R), MYH9, and BCL11B were associated with regulation of immune
      response. Meanwhile, CD4 (degree=25), perforin 1 (PRF1) (degree=15), PTPRC
      (degree=13), and CD247 (degree=9) had higher connectivity degrees in the PPI
      network for the DEGs. And they might be involved in AS by interacting with other
      genes in module B (eg, PTPRC-IL7R, CD3G-CD247, and PRF1-PTPRC). CONCLUSION: MYH9,
      BCL11B, PTPRC, CD3G, CD247, CD4, IL7R, and PRF1 might have a correlation with AS.

PMID- 25756410
TI  - Lessons learned: critical care management of patients with Ebola in the United
      States.
AB  - OBJECTIVE: This report will describe the preparations for and the provision of
      care of two patients with Ebola virus disease in the biocontainment unit at the
      University of Nebraska Medical Center. DATA SOURCES: Patient medical records.
      STUDY SELECTION: Not applicable. DATA EXTRACTION: Not applicable. DATA SYNTHESIS:
      Not applicable. CONCLUSIONS: Safe and effective care of patients with Ebola virus
      disease requires significant communication and planning. Adherence to a
      predetermined isolation protocol is essential, including proper donning and
      doffing of personal protective equipment. Location of the patient care area and
      the logistics of laboratory testing, diagnostic imaging, and the removal of waste
      must be considered. Patients with Ebola virus disease are often dehydrated and
      need adequate vascular access for fluid resuscitation, nutrition, and phlebotomy
      for laboratory sampling. Advanced planning for acute life-threatening events and
      code status must be considered. Intensivist scheduling should account for the
      significant amount of time required for the care of patients with Ebola virus
      disease. With appropriate precautions and resources, designated hospitals in the
      United States can safely provide care for patients with Ebola virus disease.

PMID- 25756409
TI  - A sniffer-camera for imaging of ethanol vaporization from wine: the effect of
      wine glass shape.
AB  - A two-dimensional imaging system (Sniffer-camera) for visualizing the
      concentration distribution of ethanol vapor emitting from wine in a wine glass
      has been developed. This system provides image information of ethanol vapor
      concentration using chemiluminescence (CL) from an enzyme-immobilized mesh. This
      system measures ethanol vapor concentration as CL intensities from luminol
      reactions induced by alcohol oxidase and a horseradish peroxidase (HRP)-luminol
      hydrogen peroxide system. Conversion of ethanol distribution and concentration to
      two-dimensional CL was conducted using an enzyme-immobilized mesh containing an
      alcohol oxidase, horseradish peroxidase, and luminol solution. The temporal
      changes in CL were detected using an electron multiplier (EM)-CCD camera and
      analyzed. We selected three types of glasses-a wine glass, a cocktail glass, and
      a straight glass-to determine the differences in ethanol emission caused by the
      shape effects of the glass. The emission measurements of ethanol vapor from wine
      in each glass were successfully visualized, with pixel intensity reflecting
      ethanol concentration. Of note, a characteristic ring shape attributed to high
      alcohol concentration appeared near the rim of the wine glass containing 13 
      degrees C wine. Thus, the alcohol concentration in the center of the wine glass
      was comparatively lower. The Sniffer-camera was demonstrated to be sufficiently
      useful for non-destructive ethanol measurement for the assessment of food
      characteristics. 

PMID- 25756411
TI  - Enhanced perfusion during advanced life support improves survival with favorable
      neurologic function in a porcine model of refractory cardiac arrest.
AB  - OBJECTIVE: To improve the likelihood for survival with favorable neurologic
      function after cardiac arrest, we assessed a new advanced life support approach
      using active compression-decompression cardiopulmonary resuscitation plus an
      intrathoracic pressure regulator. DESIGN: Prospective animal investigation.
      SETTING: Animal laboratory. SUBJECTS: Female farm pigs (n = 25) (39 +/- 3 kg).
      INTERVENTIONS: Protocol A: After 12 minutes of untreated ventricular
      fibrillation, 18 pigs were randomized to group A-3 minutes of basic life support
      with standard cardiopulmonary resuscitation, defibrillation, and if needed 2
      minutes of advanced life support with standard cardiopulmonary resuscitation;
      group B-3 minutes of basic life support with standard cardiopulmonary
      resuscitation, defibrillation, and if needed 2 minutes of advanced life support
      with active compression-decompression plus intrathoracic pressure regulator; and
      group C-3 minutes of basic life support with active compression-decompression
      cardiopulmonary resuscitation plus an impedance threshold device, defibrillation,
      and if needed 2 minutes of advanced life support with active compression
      decompression plus intrathoracic pressure regulator. Advanced life support always
      included IV epinephrine (0.05 MUg/kg). The primary endpoint was the 24-hour
      Cerebral Performance Category score. Protocol B: Myocardial and cerebral blood
      flow were measured in seven pigs before ventricular fibrillation and then
      following 6 minutes of untreated ventricular fibrillation during sequential 5
      minutes treatments with active compression-decompression plus impedance threshold
      device, active compression-decompression plus intrathoracic pressure regulator,
      and active compression-decompression plus intrathoracic pressure regulator plus
      epinephrine. MEASUREMENTS AND MAIN RESULTS: Protocol A: One of six pigs survived
      for 24 hours in group A versus six of six in groups B and C (p = 0.002) and
      Cerebral Performance Category scores were 4.7 +/- 0.8, 1.7 +/- 0.8, and 1.0 +/-
      0, respectively (p = 0.001). Protocol B: Brain blood flow was significantly
      higher with active compression-decompression plus intrathoracic pressure
      regulator compared with active compression-decompression plus impedance threshold
      device (0.39 +/- 0.23 vs 0.27 +/- 0.14 mL/min/g; p = 0.03), whereas differences
      in myocardial perfusion were not statistically significant (0.65 +/- 0.81 vs 0.42
      +/- 0.36 mL/min/g; p = 0.23). Brain and myocardial blood flow with active
      compression-decompression plus intrathoracic pressure regulator plus epinephrine
      were significantly increased versus active compression-decompression plus
      impedance threshold device (0.40 +/- 0.22 and 0.84 +/- 0.60 mL/min/g; p = 0.02
      for both). CONCLUSION: Advanced life support with active compression
      decompression plus intrathoracic pressure regulator significantly improved
      cerebral perfusion and 24-hour survival with favorable neurologic function. These
      findings support further evaluation of this new advanced life support methodology
      in humans.

PMID- 25756412
TI  - Volatile-based short-term sedation in cardiac surgical patients: a prospective
      randomized controlled trial.
AB  - OBJECTIVE: To evaluate the differences in extubation times in a group of cardiac
      surgical patients who were anesthetized and sedated with either IV propofol or
      inhaled volatile anesthetic agents. DESIGN: This was a prospective randomized
      controlled trial performed between September 2009 and August 2011. SETTING:
      Cardiovascular ICU within a tertiary referral university-affiliated teaching
      hospital. PATIENTS: One hundred forty-one patients undergoing coronary artery
      bypass graft surgery with normal or mildly reduced left ventricular systolic
      function. INTERVENTION: Participants were randomly assigned to receive anesthesia
      and postoperative sedation using IV propofol (n = 74) or inhaled volatile
      (isoflurane or sevoflurane) anesthetic agent (n = 67). MEASUREMENTS AND MAIN
      RESULTS: Patients sedated using inhaled volatile agent displayed faster readiness
      to extubation time at 135 minutes (95-200 min) compared with those receiving IV
      propofol at 215 minutes (150-280 min) (p < 0.001). Extubation times were faster
      within the volatile group at 182 minutes (140-255 min) in comparison with
      propofol group at 291 minutes (210-420 min) (p < 0.001). The volatile group
      showed a higher prevalence of vasodilatation with hypotension and higher cardiac
      outputs necessitating greater use of vasoconstrictors. There was no difference in
      postoperative pain scores, opioid consumption, sedation score, ICU or hospital
      length of stay, or patient mortality. CONCLUSIONS: Inhaled volatile anesthesia
      and sedation facilitates faster extubation times in comparison with IV propofol
      for patient undergoing coronary artery bypass graft surgery.

PMID- 25756413
TI  - Impact of the Electronic Medical Record on Mortality, Length of Stay, and Cost in
      the Hospital and ICU: A Systematic Review and Metaanalysis.
AB  - OBJECTIVE: To evaluate effects of health information technology in the inpatient
      and ICU on mortality, length of stay, and cost. Methodical evaluation of the
      impact of health information technology on outcomes is essential for institutions
      to make informed decisions regarding implementation. DATA SOURCES: EMBASE,
      Scopus, Medline, the Cochrane Review database, and Web of Science were searched
      from database inception through July 2013. Manual review of references of
      identified articles was also completed. STUDY SELECTION: Selection criteria
      included a health information technology intervention such as computerized
      physician order entry, clinical decision support systems, and surveillance
      systems, an inpatient setting, and endpoints of mortality, length of stay, or
      cost. Studies were screened by three reviewers. Of the 2,803 studies screened, 45
      met selection criteria (1.6%). DATA EXTRACTION: Data were abstracted on the year,
      design, intervention type, system used, comparator, sample sizes, and effect on
      outcomes. Studies were abstracted independently by three reviewers. DATA
      SYNTHESIS: There was a significant effect of surveillance systems on in-hospital
      mortality (odds ratio, 0.85; 95% CI, 0.76-0.94; I=59%). All other quantitative
      analyses of health information technology interventions effect on mortality and
      length of stay were not statistically significant. Cost was unable to be
      quantitatively evaluated. Qualitative synthesis of studies of each outcome
      demonstrated significant study heterogeneity and small clinical effects.
      CONCLUSIONS: Electronic interventions were not shown to have a substantial effect
      on mortality, length of stay, or cost. This may be due to the small number of
      studies that were able to be aggregately analyzed due to the heterogeneity of
      study populations, interventions, and endpoints. Better evidence is needed to
      identify the most meaningful ways to implement and use health information
      technology and before a statement of the effect of these systems on patient
      outcomes can be made.

PMID- 25756414
TI  - The Volume-Outcome Relationship in Critically Ill Patients in Relation to the ICU
      to-Hospital Bed Ratio.
AB  - OBJECTIVES: A volume-outcome relationship in ICU patients has been suggested in
      recent studies. However, it is unclear whether the ICU-to-hospital bed ratio
      affects the volume-outcome relationship. The aim of this study is to investigate
      the relationship between hospital volume and in-hospital mortality of adult ICU
      patients in relation to the ratio of ICU beds to regular hospital beds. DESIGN:
      Retrospective cohort study. SETTING: Four hundred seventy-seven Japanese
      hospitals from 2007 to 2012 in the Japanese Diagnosis Procedure Combination
      database. PATIENTS: A total of 596,143 patients discharged from acute care
      hospitals. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We analyzed data
      from 596,143 ICU patients from 2007 through 2012 using a nationwide
      administrative database. Patients were categorized into nine subgroups (the
      tertiles of hospital volume of ICU patients combined with the tertiles of ICU-to
      hospital bed ratio). Multivariable logistic regression analyses were performed to
      examine the concurrent effects of hospital volume of ICU patients and ICU-to
      hospital bed ratio on in-hospital mortality, with adjustment for patient and
      hospital characteristics. Higher hospital volume of ICU patients and a higher ICU
      to-hospital bed ratio were independently associated with lower mortality. When
      patients were stratified by ICU-to-hospital bed ratio categories, in-hospital
      mortality was significantly lower in the high-volume subgroup (odds ratio, 0.74;
      95% CI, 0.58-0.93) compared with the low-volume subgroup in hospitals with a high
      ICU-to-hospital bed ratio. However, these relationships were not significant in
      hospitals with low ICU-to-hospital bed ratios (odds ratio, 0.94; 95% CI, 0.59
      1.50) or in hospitals with intermediate ICU-to-hospital bed ratios (odds ratio,
      0.80; 95% CI, 0.71-1.08). CONCLUSIONS: An inverse relationship between hospital
      volume of ICU patients and mortality was seen only when the ICU-to-hospital bed
      ratio was sufficiently high. Regionalization and increasing the number of ICU
      beds in referral centers may improve patient outcomes.

PMID- 25756415
TI  - Ghrelin inhibits proinflammatory responses and prevents cognitive impairment in
      septic rats.
AB  - OBJECTIVES: A novel stomach-derived peptide, ghrelin, is down-regulated in sepsis
      and its IV administration decreases proinflammatory cytokines and mitigates organ
      injury. In this study, we wanted to investigate the effects of ghrelin on
      proinflammatory responses and cognitive impairment in septic rats. DESIGN:
      Prospective, randomized, controlled experiment. SETTING: Animal basic science
      laboratory. SUBJECTS: Sprague-Dawley rats, weighing 250-300 g. INTERVENTIONS:
      Sepsis was induced by cecal ligation and puncture. Animals were randomly divided
      into four groups: sham, sham + ghrelin, cecal ligation and puncture, and cecal
      ligation and puncture + ghrelin. Saline was given subcutaneously (30 mL/kg) at 4
      and 16 hours after surgery for all rats. Septic rats were treated with
      ceftriaxone (30 mg/kg) and clindamycin (25 mg/kg) subcutaneously at 4 and 16
      hours after surgery. Ghrelin (80 MUg/kg) was administrated intraperitoneally 4
      and 16 hours after surgery in sham + ghrelin group and cecal ligation and
      puncture + ghrelin group. MEASUREMENTS AND MAIN RESULTS: The levels of
      proinflammatory cytokines in hippocampus were measured by enzyme-linked
      immunosorbent assay, and cleaved caspase-3 was detected by Western blot 24 hours
      after surgery. Neuronal apoptosis was determined by terminal deoxynucleotidyl
      transferase dUTP nick-end labeling staining 48 hours after surgery. Additional
      animals were monitored to record survival and body weight changes for 10 days
      after surgery. Survival animals underwent behavioral tasks 10 days after surgery:
      open-field, novel object recognition, and continuous multiple-trial step-down
      inhibitory avoidance task. Ghrelin significantly decreased the levels of
      proinflammatory cytokines and inhibited the activation of caspase-3 in the
      hippocampus after cecal ligation and puncture. The density of terminal
      deoxynucleotidyl transferase dUTP nick-end labeling-positive apoptotic neurons
      was significantly lowered by ghrelin. In addition, ghrelin improved the survival
      rates after cecal ligation and puncture. There were no differences in the
      distance and move time between groups in open-field task. However, the survivors
      after cecal ligation and puncture were unable to recognize the novel object and
      required more training trials to reach the acquisition criterion. All these long
      term impairments were prevented by ghrelin. CONCLUSIONS: Ghrelin inhibited
      proinflammatory responses, improved the survival rate, and prevented cognitive
      impairment in septic rats.

PMID- 25756416
TI  - One fourth of unplanned transfers to a higher level of care are associated with a
      highly preventable adverse event: a patient record review in six Belgian
      hospitals.
AB  - OBJECTIVE: The objectives of this study are to determine the prevalence and
      preventability of adverse events requiring an unplanned higher level of care,
      defined as an unplanned transfer to the ICU or an in-hospital medical emergency
      team intervention, and to assess the type and the level of harm of each adverse
      event. DESIGN: A three-stage retrospective review process of screening, record
      review, and consensus judgment was performed. SETTING: Six Belgian acute
      hospitals. PATIENTS: During a 6-month period, all patients with an unplanned need
      for a higher level of care were selected. INTERVENTIONS: The records 6-month
      period, the records of all patients with an unplanned need for a higher level of
      care were assessed by a trained clinical team consisting of a research nurse, a
      physician, and a clinical pharmacist. MEASUREMENTS AND MAIN RESULTS: Adverse
      events were found in 465 of the 830 reviewed patient records (56%). Of these, 215
      (46%) were highly preventable. The overall incidence rate of patients being
      transferred to a higher level of care involving an adverse event was 117.6 (95%
      CI, 106.9-128.3) per 100,000 patient days at risk, of which 54.4 (95% CI, 47.15
      61.65) per 100,000 patient days at risk involving a highly preventable adverse
      event. This means that 25.9% of all unplanned transfers to a higher level of care
      were associated with a highly preventable adverse event. The adverse events were
      mainly associated with drug therapy (25.6%), surgery (23.7%), diagnosis (12.4%),
      and system issues (12.4%). The level of harm varied from temporary harm (55.7%)
      to long-term or permanent impairment (19.1%) and death (25.2%). Although the
      direct causality is often hard to prove, it is reasonable to consider these
      adverse events as a contributing factor. CONCLUSION: Adverse events were found in
      56% of the reviewed records, of which almost half were considered highly
      preventable. This means that one fourth of all unplanned transfers to a higher
      level of care were associated with a highly preventable adverse event.

PMID- 25756417
TI  - Association between colistin dose and development of nephrotoxicity.
AB  - OBJECTIVE: To investigate the development of nephrotoxicity associated with
      colistin dose, and whether this relationship differs depending on renal function.
      DESIGN: A retrospective cohort study of patients who received intravenous
      colistin to treat infections caused by extensively drug-resistant Gram-negative
      microorganisms. Adult patients receiving colistin for 72 hours or longer were
      included in this study. Patients who received renal replacement therapy at
      baseline or were administered colistin for less than 3 days were excluded.
      Colistin-induced nephrotoxicity was defined as a doubling of baseline serum
      creatinine. Colistin dosing was evaluated based on both actual body weight and
      ideal body weight. SETTING: Single general hospital between 2010 and 2013.
      PATIENTS: A total number of 475 patients received colistin therapy. Of these
      patients, 329 met the inclusion criteria and were included in the analysis.
      INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: One hundred forty-three
      patients (43.5%) experienced nephrotoxicity during colistin treatment. The median
      onset time of nephrotoxicity was 6 days (interquartile range, 4-8 days). The
      patients with nephrotoxicity were older. Hematocrit and serum albumin levels were
      lower in patients with nephrotoxicity. Median daily dosing of colistin based on
      ideal body weight was significantly higher in patients with nephrotoxicity than
      in those without nephrotoxicity (4.55 vs 4.43 mg/kg/d, respectively; p=0.021).
      The cumulative dose was not different between patients with and without
      nephrotoxicity. In multiple logistic regression analysis, daily colistin dosing
      based on ideal body weight was only significantly associated with the development
      of nephrotoxicity in patients with an estimated glomerular filtration rate<60
      mL/min/1.73 m2 (odds ratio, 2.34; 95% CI, 1.22-4.5). In these affected patients,
      based on a receiver operating characteristic plot, the optimal predictive cutoff
      of colistin dose for the development of nephrotoxicity was 2.87 mg/kg/d of
      colistin, with a sensitivity of 92.3% and a specificity of 76.7%. In patients
      with estimated glomerular filtration rate>=60 mL/min/1.73 m, age, serum albumin,
      hematocrit, and use of glycopeptide were associated with the development of
      nephrotoxicity. CONCLUSIONS: Development of nephrotoxicity was significantly more
      strongly associated with the dose of colistin, but only in patients with an
      estimated glomerular filtration rate<60 mL/min/1.73 m2 and not in those with
      normal renal function.

PMID- 25756419
TI  - Systemic Inflammatory Response and Potential Prognostic Implications After Out-of
      Hospital Cardiac Arrest: A Substudy of the Target Temperature Management Trial.
AB  - OBJECTIVES: Whole-body ischemia during out-of-hospital cardiac arrest triggers
      immediate activation of inflammatory systems leading to a sepsis-like syndrome.
      The aim was to investigate the association between level of systemic inflammation
      and mortality in survivors after out-of-hospital cardiac arrest treated with
      targeted temperature management. DESIGN: Post hoc analysis. SETTING: Single
      center study of a prospective multicenter randomized study. PATIENTS: One hundred
      sixty-nine patients (99%) with available blood samples out of 171 patients
      included in the Target Temperature Management trial, randomly assigning patients
      to targeted temperature management at 33 degrees C or 36 degrees C. INTERVENTION:
      None. MEASUREMENTS AND MAIN RESULTS: At baseline and 24, 48, and 72 hours after
      out-of-hospital cardiac arrest, blood samples were obtained and screened for a
      battery of inflammatory markers. Level of interleukin-1beta, interleukin-2,
      interleukin-4, interleukin-5, interleukin-6, interleukin-9, interleukin-10,
      interleukin-12, interleukin-13, tumor necrosis factor-alpha, interferon-gamma, C
      reactive protein, and procalcitonin were measured. Mortality at 30 days was
      evaluated by Cox analysis, and the predictive capability of inflammatory markers
      was evaluated by area under the curve. Level of all inflammatory markers changed
      significantly within 72 hours after out-of-hospital cardiac arrest (all p
      values<0.001), but only procalcitonin levels showed overall differences between
      nonsurvivors and survivors (p=0.0002). At baseline, interleukin-6 was
      independently associated with mortality, whereas both interleukin-6 levels
      (hazard ratio=1.23 [1.01-1.49]; p=0.04) and procalcitonin levels (hazard
      ratio=1.20 [1.03-1.39]; p=0.02) 24 hours after out-of-hospital cardiac arrest
      were associated with 30-day mortality with no interactions between targeted
      temperature management group and levels of interleukin-6 (p=0.25) or
      procalcitonin (p=0.85). None of the other inflammatory markers were independently
      associated with mortality. Area under the curve for procalcitonin and interleukin
      6, 24 hours after out-of-hospital cardiac arrest, were 0.74 and 0.63,
      respectively. CONCLUSIONS: Level of inflammation, assessed by interleukin-6 and
      procalcitonin, was independently associated with increased mortality with the
      highest discriminative value obtained 24 hours after out-of-hospital cardiac
      arrest. Interventions aiming at decreasing level of inflammation as a way to
      improve outcome may be investigated in future studies.

PMID- 25756418
TI  - Understanding and reducing disability in older adults following critical illness.
AB  - OBJECTIVE: To review how disability can develop in older adults with critical
      illness and to explore ways to reduce long-term disability following critical
      illness. DATA SOURCES: We searched PubMed, CINAHL, Web of Science and Google
      Scholar for studies reporting disability outcomes (i.e., activities of daily
      living, instrumental activities of daily living, and mobility activities) and/or
      cognitive outcomes among patients treated in an ICU who were 65 years or older.
      We also reviewed the bibliographies of relevant citations to identify additional
      citations. STUDY SELECTION: We identified 19 studies evaluating disability
      outcomes in critically ill patients who were 65 years and older. DATA EXTRACTION:
      Descriptive epidemiologic data on disability after critical illness. DATA
      SYNTHESIS: Newly acquired disability in activities of daily living, instrumental
      activities of daily living, and mobility activities was commonplace among older
      adults who survived a critical illness. Incident dementia and less severe
      cognitive impairment were also highly prevalent. Factors related to the acute
      critical illness, ICU practices, such as heavy sedation, physical restraints, and
      immobility, as well as aging physiology, and coexisting geriatric conditions can
      combine to result in these poor outcomes. CONCLUSIONS: Older adults who survive
      critical illness have physical and cognitive declines resulting in disability at
      greater rates than hospitalized, noncritically ill and community dwelling older
      adults. Interventions derived from widely available geriatric care models in use
      outside of the ICU, which address modifiable risk factors including immobility
      and delirium, are associated with improved functional and cognitive outcomes and
      can be used to complement ICU-focused models such as the ABCDEs.

PMID- 25756420
TI  - Language development at 18 months is related to multimodal communicative
      strategies at 12 months.
AB  - The present study investigated the degree to which an infants' use of
      simultaneous gesture-speech combinations during controlled social interactions
      predicts later language development. Nineteen infants participated in a
      declarative pointing task involving three different social conditions: two
      experimental conditions (a) available, when the adult was visually attending to
      the infant but did not attend to the object of reference jointly with the child,
      and (b) unavailable, when the adult was not visually attending to neither the
      infant nor the object; and (c) a baseline condition, when the adult jointly
      engaged with the infant's object of reference. At 12 months of age measures
      related to infants' speech-only productions, pointing-only gestures, and
      simultaneous pointing-speech combinations were obtained in each of the three
      social conditions. Each child's lexical and grammatical output was assessed at 18
      months of age through parental report. Results revealed a significant interaction
      between social condition and type of communicative production. Specifically, only
      simultaneous pointing-speech combinations increased in frequency during the
      available condition compared to baseline, while no differences were found for
      speech-only and pointing-only productions. Moreover, simultaneous pointing-speech
      combinations in the available condition at 12 months positively correlated with
      lexical and grammatical development at 18 months of age. The ability to
      selectively use this multimodal communicative strategy to engage the adult in
      joint attention by drawing his attention toward an unseen event or object reveals
      12-month-olds' clear understanding of referential cues that are relevant for
      language development. This strategy to successfully initiate and maintain joint
      attention is related to language development as it increases learning
      opportunities from social interactions. 

PMID- 25756423
TI  - Couple: David Park.

PMID- 25756424
TI  - Why does the Affordable Care Act remain so unpopular?

PMID- 25756421
TI  - Regulation of lipid droplet size in mammary epithelial cells by remodeling of
      membrane lipid composition-a potential mechanism.
AB  - Milk fat globule size is determined by the size of its precursors-intracellular
      lipid droplets-and is tightly associated with its composition. We examined the
      relationship between phospholipid composition of mammary epithelial cells and the
      size of both intracellular and secreted milk fat globules. Primary culture of
      mammary epithelial cells was cultured in medium without free fatty acids
      (control) or with 0.1 mM free capric, palmitic or oleic acid for 24 h. The amount
      and composition of the cellular lipids and the size of the lipid droplets were
      determined in the cells and medium. Mitochondrial quantity and expression levels
      of genes associated with mitochondrial biogenesis and polar lipid composition
      were determined. Cells cultured with oleic and palmitic acids contained similar
      quantities of triglycerides, 3.1- and 3.8-fold higher than in controls,
      respectively (P < 0.0001). When cultured with oleic acid, 22% of the cells
      contained large lipid droplets (>3 MUm) and phosphatidylethanolamine
      concentration was higher by 23 and 63% compared with that in the control and
      palmitic acid treatments, respectively (P < 0.0001). In the presence of palmitic
      acid, only 4% of the cells contained large lipid droplets and the membrane
      phosphatidylcholine concentration was 22% and 16% higher than that in the control
      and oleic acid treatments, respectively (P < 0.0001). In the oleic acid
      treatment, approximately 40% of the lipid droplets were larger than 5 MUm whereas
      in that of the palmitic acid treatment, only 16% of the droplets were in this
      size range. Triglyceride secretion in the oleic acid treatment was 2- and 12-fold
      higher compared with that in the palmitic acid and control treatments,
      respectively. Results imply that membrane composition of bovine mammary
      epithelial cells plays a role in controlling intracellular and secreted lipid
      droplets size, and that this process is not associated with cellular triglyceride
      content. 

PMID- 25756431
TI  - Innovation and implementation in cardiovascular medicine: challenges in the face
      of opportunity.

PMID- 25756432
TI  - Deciphering cholesterol treatment guidelines: a clinician's perspective.

PMID- 25756433
TI  - Statin intolerance: reconciling clinical trials and clinical experience.

PMID- 25756434
TI  - Are new oral anticoagulant dosing recommendations optimal for all patients?

PMID- 25756435
TI  - A piece of my mind. Insight on the Irrawaddy.

PMID- 25756436
TI  - Does the LDL receptor play a role in the risk of developing type 2 diabetes?

PMID- 25756438
TI  - Clinical outcomes at 1 year following transcatheter aortic valve replacement.
AB  - IMPORTANCE: Introducing new medical devices into routine practice raises concerns
      because patients and outcomes may differ from those in randomized trials.
      OBJECTIVE: To update the previous report of 30-day outcomes and present 1-year
      outcomes following transcatheter aortic valve replacement (TAVR) in the United
      States. DESIGN, SETTING, AND PARTICIPANTS: Data from the Society of Thoracic
      Surgeons/American College of Cardiology (STS/ACC) Transcatheter Valve Therapies
      Registry were linked with patient-specific Centers for Medicare & Medicaid
      Services (CMS) administrative claims data. At 299 US hospitals, 12 182 patients
      linked with CMS data underwent TAVR procedures performed from November 2011
      through June 30, 2013, and the end of the follow-up period was June 30, 2014.
      EXPOSURE: Transcatheter aortic valve replacement. MAIN OUTCOMES AND MEASURES: One
      year outcomes including mortality, stroke, and rehospitalization were evaluated
      using multivariate modeling. RESULTS: The median age of patients was 84 years and
      52% were women, with a median STS Predicted Risk of Operative Mortality (STS
      PROM) score of 7.1%. Following the TAVR procedure, 59.8% were discharged to home
      and the 30-day mortality was 7.0% (95% CI, 6.5%-7.4%) (n = 847 deaths). In the
      first year after TAVR, patients were alive and out of the hospital for a median
      of 353 days (interquartile range, 312-359 days); 24.4% (n = 2074) of survivors
      were rehospitalized once and 12.5% (n = 1525) were rehospitalized twice. By 1
      year, the overall mortality rate was 23.7% (95% CI, 22.8%-24.5%) (n = 2450
      deaths), the stroke rate was 4.1% (95% CI, 3.7%-4.5%) (n = 455 stroke events),
      and the rate of the composite outcome of mortality and stroke was 26.0% (25.1%
      26.8%) (n = 2719 events). Characteristics significantly associated with 1-year
      mortality included advanced age (hazard ratio [HR] for >=95 vs <75 years, 1.61
      [95% CI, 1.24-2.09]; HR for 85-94 years vs <75 years, 1.35 [95% CI, 1.18-1.55];
      and HR for 75-84 years vs <75 years, 1.23 [95% CI, 1.08-1.41]), male sex (HR,
      1.21; 95% CI, 1.12-1.31), end-stage renal disease (HR, 1.66; 95% CI, 1.41-1.95),
      severe chronic obstructive pulmonary disease (HR, 1.39; 95% CI, 1.25-1.55),
      nontransfemoral access (HR, 1.37; 95% CI, 1.27-1.48), STS PROM score greater than
      15% vs less than 8% (HR, 1.82; 95% CI, 1.60-2.06), and preoperative atrial
      fibrillation/flutter (HR, 1.37; 95% CI, 1.27-1.48). Compared with men, women had
      a higher risk of stroke (HR, 1.40; 95% CI, 1.15-1.71). CONCLUSIONS AND RELEVANCE:
      Among patients undergoing TAVR in US clinical practice, at 1-year follow-up,
      overall mortality was 23.7%, the stroke rate was 4.1%, and the rate of the
      composite outcome of death and stroke was 26.0%. These findings should be helpful
      in discussions with patients undergoing TAVR.

PMID- 25756439
TI  - Association between familial hypercholesterolemia and prevalence of type 2
      diabetes mellitus.
AB  - IMPORTANCE: Familial hypercholesterolemia is characterized by impaired uptake of
      cholesterol in peripheral tissues, including the liver and the pancreas. In
      contrast, statins increase the cellular cholesterol uptake and are associated
      with increased risk for type 2 diabetes mellitus. We hypothesize that
      transmembrane cholesterol transport is linked to the development of type 2
      diabetes. OBJECTIVE: To assess the association between type 2 diabetes prevalence
      and familial hypercholesterolemia. DESIGN, SETTING, AND PARTICIPANTS: Cross
      sectional study in all individuals (n = 63,320) who underwent DNA testing for
      familial hypercholesterolemia in the national Dutch screening program between
      1994 and 2014. EXPOSURES: Deleteriousness and nondeleteriousness of familial
      hypercholesterolemia mutations were based on literature or laboratory function
      testing. Low-density lipoprotein (LDL) receptor mutations were considered more
      severe than apolipoprotein B gene (APOB) mutations, and receptor-negative LDL
      receptor mutations were considered more severe than receptor-deficient mutations.
      MAIN OUTCOMES AND MEASURES: Prevalence of type 2 diabetes. RESULTS: The
      prevalence of type 2 diabetes was 1.75% in familial hypercholesterolemia patients
      (n = 440/25,137) vs 2.93% in unaffected relatives (n = 1119/38,183) (P < .001;
      odds ratio [OR], 0.62 [95% CI, 0.55-0.69]). The adjusted prevalence of type 2
      diabetes in familial hypercholesterolemia, determined using multivariable
      regression models, was 1.44% (difference, 1.49% [95% CI, 1.24%-1.71%]) (OR, 0.49
      [95% CI, 0.41-0.58]; P < .001). The adjusted prevalence of type 2 diabetes by
      APOB vs LDL receptor gene was 1.91% vs 1.33% (OR, 0.65 [95% CI, 0.48-0.87] vs OR,
      0.45 [95% CI, 0.38-0.54]), and the prevalence for receptor-deficient vs receptor
      negative mutation carriers was 1.44% vs 1.12% (OR, 0.49 [95% CI, 0.40-0.60] vs
      OR, 0.38 [95% CI, 0.29-0.49]), respectively (P for trend <.001 in both
      comparisons). CONCLUSIONS AND RELEVANCE: In a cross-sectional analysis in the
      Netherlands, the prevalence of type 2 diabetes among patients with familial
      hypercholesterolemia was significantly lower than among unaffected relatives,
      with variability by mutation type. If this finding is confirmed in longitudinal
      analysis, it would raise the possibility of a causal relationship between LDL
      receptor-mediated transmembrane cholesterol transport and type 2 diabetes.

PMID- 25756441
TI  - Food antioxidants to prevent cataract.

PMID- 25756440
TI  - Surgical vs nonsurgical treatment of adults with displaced fractures of the
      proximal humerus: the PROFHER randomized clinical trial.
AB  - IMPORTANCE: The need for surgery for the majority of patients with displaced
      proximal humeral fractures is unclear, but its use is increasing. OBJECTIVE: To
      evaluate the clinical effectiveness of surgical vs nonsurgical treatment for
      adults with displaced fractures of the proximal humerus involving the surgical
      neck. DESIGN, SETTING, AND PARTICIPANTS: A pragmatic, multicenter, parallel
      group, randomized clinical trial, the Proximal Fracture of the Humerus Evaluation
      by Randomization (PROFHER) trial, recruited 250 patients aged 16 years or older
      (mean age, 66 years [range, 24-92 years]; 192 [77%] were female; and 249 [99.6%]
      were white) who presented at the orthopedic departments of 32 acute UK National
      Health Service hospitals between September 2008 and April 2011 within 3 weeks
      after sustaining a displaced fracture of the proximal humerus involving the
      surgical neck. Patients were followed up for 2 years (up to April 2013) and 215
      had complete follow-up data. The data for 231 patients (114 in surgical group and
      117 in nonsurgical group) were included in the primary analysis. INTERVENTIONS:
      Fracture fixation or humeral head replacement were performed by surgeons
      experienced in these techniques. Nonsurgical treatment was sling immobilization.
      Standardized outpatient and community-based rehabilitation was provided to both
      groups. MAIN OUTCOMES AND MEASURES: Primary outcome was the Oxford Shoulder Score
      (range, 0-48; higher scores indicate better outcomes) assessed during a 2-year
      period, with assessment and data collection at 6, 12, and 24 months. Sample size
      was based on a minimal clinically important difference of 5 points for the Oxford
      Shoulder Score. Secondary outcomes were the Short-Form 12 (SF-12), complications,
      subsequent therapy, and mortality. RESULTS: There was no significant mean
      treatment group difference in the Oxford Shoulder Score averaged over 2 years
      (39.07 points for the surgical group vs 38.32 points for the nonsurgical group;
      difference of 0.75 points [95% CI, -1.33 to 2.84 points]; P = .48) or at
      individual time points. There were also no significant between-group differences
      over 2 years in the mean SF-12 physical component score (surgical group: 1.77
      points higher [95% CI, -0.84 to 4.39 points]; P = .18); the mean SF-12 mental
      component score (surgical group: 1.28 points lower [95% CI, -3.80 to 1.23
      points]; P = .32); complications related to surgery or shoulder fracture (30
      patients in surgical group vs 23 patients in nonsurgical group; P = .28),
      requiring secondary surgery to the shoulder (11 patients in both groups), and
      increased or new shoulder-related therapy (7 patients vs 4 patients,
      respectively; P = .58); and mortality (9 patients vs 5 patients; P = .27). Ten
      medical complications (2 cardiovascular events, 2 respiratory events, 2
      gastrointestinal events, and 4 others) occurred in the surgical group during the
      postoperative hospital stay. CONCLUSIONS AND RELEVANCE: Among patients with
      displaced proximal humeral fractures involving the surgical neck, there was no
      significant difference between surgical treatment compared with nonsurgical
      treatment in patient-reported clinical outcomes over 2 years following fracture
      occurrence. These results do not support the trend of increased surgery for
      patients with displaced fractures of the proximal humerus. TRIAL REGISTRATION:
      isrctn.com Identifier: ISRCTN50850043.

PMID- 25756443
TI  - Drugs for chronic heart failure.

PMID- 25756442
TI  - Doppler echocardiography in the evaluation of a heart murmur.

PMID- 25756444
TI  - Readmission diagnoses after hospitalization for severe sepsis and other acute
      medical conditions.

PMID- 25756445
TI  - Left atrial appendage closure for atrial fibrillation.

PMID- 25756446
TI  - Left atrial appendage closure for atrial fibrillation--reply.

PMID- 25756447
TI  - Medical liability and reporting malpractice payments.

PMID- 25756448
TI  - Medical liability and reporting malpractice payments--reply.

PMID- 25756449
TI  - Preventing prescription opioid abuse.

PMID- 25756450
TI  - Preventing prescription opioid abuse.

PMID- 25756451
TI  - Preventing prescription opioid abuse--reply.

PMID- 25756454
TI  - The Irish physician as a poet.

PMID- 25756455
TI  - Irish physician-poets.

PMID- 25756456
TI  - JAMA patient page. Atrial fibrillation.

PMID- 25756457
TI  - Unilateral loss of spontaneous venous pulsations in an astronaut.

PMID- 25756458
TI  - Evaluation of angiogenesis, epithelialisation and microcirculation after
      application of polyhexanide, chitosan and sodium chloride in rodents.
AB  - The purpose of this study was to investigate the effect of polyhexanide and a new
      developed chitin-based wound dressing on skin microcirculation, epithelialisation
      and angiogenesis. A full-thickness dermal layer extending to the underlying
      cartilage was excised on the dorsal side of hairless mice (n = 27; 2.3 +/- 0.3
      mm2 ). A polyhexanide ointment, a chitosan solution and a sodium chloride group
      as control were analysed using intravital fluorescence microscopy. Angiogenesis,
      epithelialisation and microcirculatory standard parameters were measured over a
      time period of 20 days. The non-perfused area is regarded as a parameter for
      angiogenesis and showed the following results: on days 12, 16 and 20, the sodium
      chloride group was significantly superior to chitosan solution (P < 0.05) and, on
      days 8, 12, 16 and 20, the polyhexanide group was superior to chitosan solution
      (P < 0.05). The epithelialisation was measured significantly faster in the
      polyhexanide and control group on day 8 versus chitosan solution. Whereas
      polyhexanide and sodium chloride were nearly completely epithelialised, treatment
      with chitosan solution showed still an open wound of 11% of the initial wound
      size. Altogether, we could demonstrate the advantageous effects of a polyhexanide
      ointment on microcirculation, angiogenesis and epithelialisation. Chitosan
      solution appears to inhibit angiogenesis and delays epithelialisation. Further
      studies in different models would be worthwhile to confirm these results.

PMID- 25756459
TI  - Assessing the effects of tinnitus retraining therapy in patients lost to follow
      up: a telephone survey.
AB  - OBJECTIVE: To evaluate the efficacy of tinnitus retraining therapy (TRT),
      especially in patients who did not revisit the clinic after starting the program,
      and to determine the current status of patients who were lost to follow-up. STUDY
      DESIGN: Telephone survey. SETTING: Tertiary referral center. PATIENTS: Forty
      seven patients enrolled in a TRT program at Seoul National University Hospital.
      Twenty-four patients who regularly visited the clinic were deemed the good follow
      up (GF) group, and 23 patients who did not return after the initial counseling
      were deemed the follow-up loss (FL) group. INTERVENTIONS: Post-TRT questionnaires
      with the Tinnitus Handicap Inventory (THI) and a tinnitus visual analog scale
      (VAS), performed with a telephone survey. MAIN OUTCOME MEASURES: TRT efficacy,
      evaluated via the THI, and tinnitus VAS scores. A questionnaire on reasons for
      non-attendance after TRT was used. RESULTS: Pre-TRT VAS and THI scores showed no
      significant difference between groups. After TRT, both groups showed significant
      decreases in tinnitus VAS and THI scores. Post-TRT VAS scores for awareness,
      effects on daily life, and post-TRT THI scores were significantly lower in the FL
      group. CONCLUSIONS: Treatment outcomes were better in the FL group than in the GF
      group in several parameters. The FL group was greatly influenced by the first TRT
      counseling and obtained sufficient relief that they no longer felt the need for
      additional treatment. Treatment outcomes in patients lost to follow-up may not be
      as bad as presumed.

PMID- 25756460
TI  - Long-Term Results of TORP-Vibroplasty.
AB  - OBJECTIVE: Assessing long-term results of patients treated with total ossicular
      replacement prosthesis (TORP)-vibroplasty. DESIGN: Retrospective analysis.
      SETTING: Tertiary referral center. PATIENTS: A total of five patients (two women,
      three men; mean age, 66 yr) were eligible for evaluation after an average follow
      up period of 5.1 years after TORP-vibroplasty. INTERVENTIONS: Implantation of an
      active middle ear device in conjunction with a titanium coupler for oval window
      placement in patients with chronic middle ear disease with missing stapes
      suprastructure. MAIN OUTCOME MEASURES: Audiometric outcomes and satisfaction of
      the patients. RESULTS: The functional gain was 45.2 and 45.6 dB HL at 6 months
      and 5.1 years after implantation, respectively. The speech recognition using the
      Freiburg monosyllabic word test and speech intelligibility showed postoperatively
      a distinct improvement and revealed no statistically significant change across
      time for the entire follow-up period. According to the International Outcome
      Inventory for Hearing Aids questionnaire, the patients stated considerable
      subjective benefits and satisfaction with the device. CONCLUSION: The good
      outcomes of TORP-vibroplasty in chronic disabled ears are stable. They provide
      long-term and long-lasting satisfying audiologic results combined with a high
      satisfaction of the patient. Prerequisite is the stable attachment to the
      cochlear windows.

PMID- 25756461
TI  - Dilemmas in the treatment of concurrent bilateral meningoencephalocele and
      superior semicircular canal dehiscence.
AB  - OBJECTIVE: To report on a patient with bilateral meningoencephalocele complicated
      by bilateral asymptomatic superior semicircular canal dehiscence and discuss
      dilemmas associated with his successful surgical treatment. STUDY DESIGN: Case
      capsule report. SETTING: Tertiary academic medical center. PATIENT: A 56-year-old
      man with 6 years of progressive conductive hearing loss and recent spontaneous
      cerebrospinal fluid leak from the right ear diagnosed as having bilateral large
      temporal bone meningoencephalocele (ME) and concomitant bilateral asymptomatic
      superior semicircular canal dehiscence (SSCD). RESULTS: The right ME was repaired
      through the middle fossa approach, and the right SSCD was plugged. To avoid the
      risk associated with bilaterally plugging the SSCDs, the left ME was sealed by
      subtotal petrosectomy, blind sac closure of the external auditory canal, plugging
      of the eustachian tube orifice, and obliteration of the residual space with an
      abdominal fat graft. The herniated brain and meninges were amputated, and the
      tissue present in the attic was not disrupted. Hearing was reconstructed with a
      two-staged Bone-anchored Hearing Aid procedure to avoid the risk of cerebrospinal
      fluid leaking through the skin defect of the Bone-anchored Hearing Aid abutment.
      CONCLUSION: Temporal bone ME can be associated with asymptomatic SSCD. We
      illustrate an example of how patients with bilateral pathologies can be managed
      effectively with good vestibular, auditory, and cosmetic results.

PMID- 25756462
TI  - Melting of highly oriented fiber DNA subjected to osmotic pressure.
AB  - A pilot study of the possibility to investigate temperature-dependent neutron
      scattering from fiber-DNA in solution is presented. The study aims to establish
      the feasibility of experiments to probe the influence of spatial confinement on
      the structural correlation and the formation of denatured bubbles in DNA during
      the melting transition. Calorimetry and neutron scattering experiments on fiber
      samples immersed in solutions of poly(ethylene glycol) (PEG) prove that the
      melting transition occurs in these samples, that the transition is reversible to
      some degree, and that the transition is broader in temperature than for
      humidified fiber samples. The PEG solutions apply an osmotic pressure that
      maintains the fiber orientation, establishing the feasibility of future
      scattering experiments to study the melting transition in these samples. 

PMID- 25756463
TI  - Third-party punishers are rewarded, but third-party helpers even more so.
AB  - Punishers can benefit from a tough reputation, where future partners cooperate
      because they fear repercussions. Alternatively, punishers might receive help from
      bystanders if their act is perceived as just and other-regarding. Third-party
      punishment of selfish individuals arguably fits these conditions, but it is not
      known whether third-party punishers are rewarded for their investments. Here, we
      show that third-party punishers are indeed rewarded by uninvolved bystanders.
      Third parties were presented with the outcome of a dictator game in which the
      dictator was either selfish or fair and were allocated to one of three treatments
      in which they could choose to do nothing or (1) punish the dictator, (2) help the
      receiver, or (3) choose between punishment and helping, respectively. A fourth
      player (bystander) then sees the third-party's decision and could choose to
      reward the third party or not. Third parties that punished selfish dictators were
      more likely to be rewarded by bystanders than third parties that took no action
      in response to a selfish dictator. However, helpful third parties were rewarded
      even more than third-party punishers. These results suggest that punishment could
      in principle evolve via indirect reciprocity, but also provide insights into why
      individuals typically prefer to invest in positive actions. 

PMID- 25756464
TI  - Planar N-heterocyclic carbene diarylborenium ions: synthesis by cationic
      borylation and reactivity with Lewis bases.
AB  - The NHC-borane adduct (IBn)BH3 (1) (NHC= N-heterocyclic carbene; IBn=1,3
      dibenzylimidazol-2ylidene) reacts with [Ph3 C][B(C6 F5 )4 ] through sequential
      hydride abstraction and dehydrogenative cationic borylation(s) to give singly or
      doubly ring closed NHC-borenium salts 2 and 3. The planar doubly ring closed
      product [C3 H2 (NCH2 C6 H4 )2 B][B(C6 F5 )4 ] is resistant to quaternization at
      boron by Et2 O coordination, but forms classical Lewis acid-base adducts with the
      stronger donors Ph3 P, Et3 PO, or 1,4-diazabicyclo[2.2.2]octane (DABCO).
      Treatment of 3 with tBu3 P selectively yields the unusual oligomeric borenium
      salt trans-[(C3 H2 (NCH2 C6 H4 )2 B)2 (C3 H2 (NCHC6 H4 )2 B)][B(C6 F5 )4 ] (7). 

PMID- 25756465
TI  - Supplementation of chitosan alleviates high-fat diet-enhanced lipogenesis in rats
      via adenosine monophosphate (AMP)-activated protein kinase activation and
      inhibition of lipogenesis-associated genes.
AB  - This study investigated the role of chitosan in lipogenesis in high-fat diet
      induced obese rats. The lipogenesis-associated genes and their upstream
      regulatory proteins were explored. Diet supplementation of chitosan efficiently
      decreased the increased weights in body, livers, and adipose tissues in high-fat
      diet-fed rats. Chitosan supplementation significantly raised the lipolysis rate;
      attenuated the adipocyte hypertrophy, triglyceride accumulation, and lipoprotein
      lipase activity in epididymal adipose tissues; and decreased hepatic enzyme
      activities of lipid biosynthesis. Chitosan supplementation significantly
      activated adenosine monophosphate (AMP)-activated protein kinase (AMPK)
      phosphorylation and attenuated high-fat diet-induced protein expressions of
      lipogenic transcription factors (PPAR-gamma and SREBP1c) in livers and adipose
      tissues. Moreover, chitosan supplementation significantly inhibited the
      expressions of downstream lipogenic genes (FAS, HMGCR, FATP1, and FABP4) in
      livers and adipose tissues of high-fat diet-fed rats. These results demonstrate
      for the first time that chitosan supplementation alleviates high-fat diet
      enhanced lipogenesis in rats via AMPK activation and lipogenesis-associated gene
      inhibition. 

PMID- 25756466
TI  - Biophysical comparison of soluble amyloid-beta(1-42) protofibrils, oligomers, and
      protofilaments.
AB  - Some of the pathological hallmarks of the Alzheimer's disease brain are senile
      plaques composed of insoluble amyloid-beta protein (Abeta) fibrils. However, much
      of the recent emphasis in research has been on soluble Abeta aggregates in
      response to a growing body of evidence that shows that these species may be more
      neurotoxic than fibrils. Within this subset of soluble aggregated Abeta are
      protofibrils and oligomers. Although each species has been widely investigated
      separately, few studies have directly compared and contrasted their physical
      properties. In this work, we examined well-recognized preparations of Abeta(1-42)
      oligomers and protofibrils with multiangle (MALS) and dynamic (DLS) light
      scattering in line with, or following, size-exclusion chromatography (SEC).
      Multiple SEC-MALS analyses of protofibrils revealed molecular weight (Mw)
      gradients ranging from 200 to 2600 kDa. Oligomeric Abeta species are generally
      considered to be a smaller and more nascent than protofibrils. However, oligomer
      Mw values ranged from 225 to 3000 kDa, larger than that for protofibrils. Root
      mean-square radius (Rg) values correlated with the Mw trends with protofibril Rg
      values ranging from 16 to 35 nm, while oligomers produced one population at 40-43
      nm with a more disperse population from 22 to 39 nm. Hydrodynamic radius (RH)
      measurements by DLS and thioflavin T fluorescence measurements indicated that
      protofibrils and oligomers had commonalities, yet electron microscopy revealed
      morphological differences between the two. SEC-purified Abeta(1-42) monomer at
      lower concentrations was slower to nucleate but formed protofibrils (1500 kDa) or
      soluble protofilaments (3000 kDa) depending on the buffer type. The findings from
      these studies shed new light on the similarities and differences between distinct
      soluble aggregated Abeta species. 

PMID- 25756467
TI  - Trimetazidine in Practice: Review of the Clinical and Experimental Evidence.
AB  - All of the following traditional agents for the management of stable angina
      pectoris include the symptomatic treatment with heart rate-lowering agents such
      as beta-blockers or non-dihydropyridine Ca-channel blockers, or ivabradine-the
      first selective sinus node If channel inhibitor-vasodilatators and preventive use
      of angiotensin-converting enzyme inhibitors affect the parameters of circulation
      directly. Trimetazidine exerts its anti-ischemic action by modulating cardiac
      metabolism without altering the hemodynamic functions, therefore represents an
      excellent complementary potential to the conventional angina treatment. It has a
      beneficial effect on the inflammatory profile and endothelial function and shows
      diverse benefits by reducing the number and the intensity of angina attacks and
      improving the clinical signs and symptoms of myocardial ischemia given as
      monotherapy as well as combined with other antianginal agents. Patients
      undergoing coronary revascularization procedures or with comorbid left
      ventricular dysfunction and diabetes mellitus also benefit from the protective
      effects of trimetazidine. 

PMID- 25756468
TI  - Acute Pancreatitis Associated With Ado-Trastuzumab Emtansine.
AB  - Ado-trastuzumab emtansine (T-DM1) is a novel antibody-drug conjugate with current
      FDA recommendation for second-line treatment of HER-2-positive metastatic breast
      cancer. It is a human epidermal growth factor receptor (HER-2)-targeted antibody
      drug conjugate composed of trastuzumab, a stable thioether linker, and the potent
      cytotoxic agent DM1 (derivative of maytansine). Ado-trastuzumab emtansine
      improved both progression-free and overall survival as reported in EMILIA trial.
      With ongoing clinical trials in adjuvant and first-line setting for HER-2
      positive early and metastatic breast cancer, it is prudent to recognize, report,
      and treat any adverse events related to T-DM1. We report a case of acute
      pancreatitis in a 54-year-old woman with metastatic breast cancer after she
      received her first dose of ado-trastuzumab emtansine. To the best of our
      knowledge, this is the first reported case of acute pancreatitis with probable
      association with ado-trastuzumab emtansine. 

PMID- 25756469
TI  - Temporal and Geographic Variations in the Receipt of Colony-Stimulating Factors
      and Erythropoiesis-Stimulating Agents in a Large Retrospective Cohort of Older
      Women With Breast Cancer From 2000 to 2009.
AB  - The purpose of this study was to use the most recent national data for a large
      cohort of patients diagnosed with breast cancer to evaluate temporal trend of
      receiving hematopoietic growth factors from 2000 to 2009 and to examine
      significant factors associated with increasing trends and geographic variations.
      We identified 26,130 women aged 65-89 years who were diagnosed with breast cancer
      and received chemotherapy in 2000-2009 from the Surveillance, Epidemiology, and
      End Results (SEER)-Medicare data. Colony-stimulating factors (CSFs) were
      identified if there was a claim from the following procedure codes: filgrastim,
      pegfilgrastim, or sargramostim. Erythropoiesis-stimulating agents (ESAs) were
      identified if there was a claim from the following procedure codes: epoetin or
      darbepoetin. Overall, 51.7% of patients with breast cancer received CSFs, which
      increased from 21.7% in 2000 to 63.2% in 2009. The percentage of patients
      receiving pegfilgrastim increased from 2.7% in 2000 to 19.5% in 2003 and then
      continuously to 49.7% in 2009. The overall percentage of patients receiving ESAs
      was 39.3%, which increased from 26.4% in 2000 to 60.8% in 2006, and then
      decreased significantly from 40.7% in 2007 to 12.9% in 2009. The receipt of both
      CSFs and ESAs differed significantly across different geographic areas. The
      receipt of CSFs continued to increase from 2000 to 2009, and pegfilgrastim
      started to replace filgrastim since 2003. The receipt of ESAs increased until
      2006 and then declined substantially due to the black box warning. There were
      substantial geographic variations in the use of these hematopoietic growth
      factors. 

PMID- 25756470
TI  - Metformin-Induced Hemolytic Anemia in a Patient With Glucose-6-Phosphate
      Dehydrogenase Deficiency.
AB  - Metformin, an oral antidiabetic agent, is considered the preferred first-line
      therapy for patients with type II diabetes. Between 2010 and 2012, it has been
      estimated that 14 million Americans were administered an oral antidiabetic agent,
      suggesting the extensive use of metformin among the diabetic population. There
      have been few case reports implicating metformin in causing hemolytic anemia. We
      present a case of a 53-year-old white male who developed hemolytic anemia after
      the initiation of treatment with metformin 500 mg twice daily. The patient
      experienced a 1.5 g/dL decrease in hemoglobin from baseline and a 2.8 mg/dL
      increase in total bilirubin within 1 day of treatment. Laboratory results
      confirmed that the patient was also glucose-6-phosphate dehydrogenase deficient.
      The hemolytic anemia resolved on discontinuation of metformin. Although this
      adverse effect seems to be rare, it is important to consider its seriousness.
      Clinicians should be advised to closely monitor patients newly started on
      metformin. 

PMID- 25756471
TI  - "Krokodil"-a menace slowly spreading across the Atlantic.
AB  - Krokodil (also known as crocodile, croc, krok, and poor man's heroin) is a
      suspension of desomorphine as the core substance with contaminants like iodide,
      phosphorous, and heavy metals, which are the byproducts of the manufacturing
      process. The name krokodil emerged due to the appearance of the skin lesions
      around the injection site, where it turns green and scaly like a crocodile skin
      due to desquamation. It is also known as the "drug that eats junkies" and
      "Russia's Designer drug." It is not available as a prescription anywhere in the
      world. It is a modern day man-made Frankenstein-like drug, which was manufactured
      due to the pursuit of drug addicts to make a cheap yet effective narcotic but
      ended up in creating havoc on its users. It has devastating effects on its users,
      including damage to skin, blood vessels, muscles, bones, and sometimes even
      multiorgan failure and eventually death. A systemic review was conducted to
      obtain any available data for the term krokodil to collect information for this
      article.

PMID- 25756472
TI  - Estimating air travel-associated importations of dengue virus into Italy.
AB  - BACKGROUND: Southern Europe is increasingly at risk for dengue emergence, given
      the seasonal presence of relevant mosquito vectors and suitable climatic
      conditions. For example, Aedes mosquitoes, the main vector for both dengue and
      chikungunya, are abundant in Italy, and Italy experienced the first ever outbreak
      of chikungunya in Europe in 2007. We set out to estimate the extent of dengue
      virus importations into Italy via air travelers. METHODS: We attempted to
      quantify the number of dengue virus importations based on modeling of published
      estimates on dengue incidence in the countries of disembarkation and analysis of
      data on comprehensive air travel from these countries into Italy's largest
      international airport in Rome. RESULTS: From 2005 to 2012, more than 7.3 million
      air passengers departing from 100 dengue-endemic countries arrived in Rome. Our
      Importation Model, which included air traveler volume, estimated the incidence of
      dengue infections in the countries of disembarkation, and the probability of
      infection coinciding with travel accounted for an average of 2,320 (1,621-3,255)
      imported dengue virus infections per year, of which 572 (381-858) were "apparent"
      dengue infections and 1,747 (1,240-2,397) "inapparent." CONCLUSIONS: Between 2005
      and 2012, we found an increasing trend of dengue virus infections imported into
      Rome via air travel, which may pose a potential threat for future emergence of
      dengue in Italy, given that the reoccurring pattern of peak importations
      corresponds seasonally with periods of relevant mosquito vector activity. The
      observed increasing annual trends of dengue importation and the consistent peaks
      in late summer underpin the urgency in determining the threshold levels for the
      vector and infected human populations that could facilitate novel autochthonous
      transmission of dengue in Europe.

PMID- 25756474
TI  - Review of Clinical Pharmacology of Aloe vera L. in the Treatment of Psoriasis.
AB  - Aloe vera L., is a plant used worldwide as folk remedy for the treatment of
      various ailments, including skin disorders. Its gel is present in cosmetics,
      medicinal products and food supplements. Psoriasis, an immune-mediated chronic
      inflammatory disease, involving mainly the skin, affects about the 2-3% of
      general population. Conventional pharmacological treatments for psoriasis can
      have limited effectiveness and can cause adverse reactions. For this reason often
      psoriatic patients look for alternative treatments based on natural products
      containing Aloe vera. We conducted a systematic review of clinical trials
      assessing effectiveness and safety of aloe for the treatment of psoriasis.
      Clinical studies published in English were considered; a total of four clinical
      trials met inclusion criteria. Studies were also evaluated by using the Jadad
      scale and Consort Statement in Reporting Clinical trials of Herbal Medicine
      Intervention. Quality and methodological accuracy of considered studies varied
      considerably, and some crucial information to reproduce clinical results was
      missing. We conclude that administration of aloe as cutaneous treatment is
      generally well tolerated, as no serious side effects were reported. Results on
      the effectiveness of Aloe vera are contradictory; our analysis reveals the
      presence of methodological gaps preventing to reach final conclusions.

PMID- 25756473
TI  - Complex renal cysts associated with crizotinib treatment.
AB  - An apparent causal association between crizotinib treatment and renal cyst
      development emerged during clinical trials in anaplastic lymphoma kinase (ALK)
      positive non-small cell lung cancer (NSCLC). Serious adverse event (SAE) reports
      of renal cysts from a safety database of 1375 patients from four clinical trials
      were reviewed. A blinded, retrospective, independent radiologic review (IRR) was
      performed using scans from patients on study for >= 6 months in three clinical
      trials; risk factors for renal cyst development were assessed. Among 17 patients
      with renal cysts reported as SAEs, evidence of invasion into adjacent structures
      was noted in seven patients, with no evidence of malignancy found. These patients
      generally did not require dose reductions, none required permanent crizotinib
      discontinuation due to this AE, and most continued treatment with clinical
      benefit. In the blinded IRR, among 255 crizotinib-treated patients, 22%, 3%, and
      2% had preexisting simple cysts, complex cysts, or both, respectively. At the 6
      month tumor assessment, 9% of all patients had acquired new cysts, and 2% of
      patients with preexisting cysts had developed new cysts and enlargements (>50%)
      of preexisting simple cysts. Asians appeared to have an increased risk of
      developing new cysts on treatment; Koreans in particular had 5.18 times higher
      odds of developing cysts than non-Asians (95% confidence interval, 1.51-17.78; P
      = 0.05). Crizotinib treatment appears to be associated with an increased risk of
      development and progression of renal cysts in patients with ALK-positive NSCLC.
      While close monitoring is recommended, dosing modification was not generally
      necessary, allowing patients to remain on crizotinib treatment.

PMID- 25756475
TI  - Topical treatment of melanoma skin metastases with imiquimod: a review.
AB  - BACKGROUND: At present, case studies are the only source of results on imiquimod
      (IMQ) as monotherapy in cutaneous metastases from melanoma. We analyzed these
      studies in the literature with the aim to review the efficacy of IMQ as topical
      treatment for melanoma skin metastases. OBJECTIVE: The aim of our review was to
      critically assess the studies evaluating the monotherapy with IMQ cream in the
      treatment of cutaneous metastases from melanoma. METHODS: A PubMed search was
      conducted using the term "melanoma" combined with "metastases" and "imiquimod".
      RESULTS: 57 studies were identified. 46 did not meet inclusion criteria, leaving
      11 case studies. Overall, 17 patients were treated in these 11 studies. Main
      treatment choice was 5% IMQ cream applied once daily (for 6-8 hours), five days
      per week under occlusive conditions, in 8/17 patients (47,1%). IMQ was applied 3
      times weekly in 4/17 patients (23,53%), daily in 2/17 patients (11,76%) and twice
      daily in 2/17 patients (11,76%). Treatment length was variable, with a mean
      duration of 22 weeks (range from 8 weeks to 72 weeks). The majority of studies
      showed that IMQ is an effective and safe treatment for metastases of melanoma.
      Even if this treatment doesn't stop the disease progression, it is mainly useful
      in clearing cutaneous metastases spreading from melanoma primary tumor.

PMID- 25756476
TI  - TNF-inhibitor induced lupus in a patient treated with adalimumab for rheumatoid
      arthritis.
AB  - Anti-tumor necrosis factor induced lupus (ATIL) is a rare side effect reported in
      patients treated with anti-tumor necrosis factor medications such as infliximab,
      etanercept and adalimumab. Of the three, this condition has been least commonly
      reported secondary to adalimumab. In this report, we present a case of ATIL in a
      patient treated for rheumatoid arthritis (RA) with adalimumab. This report will
      increase physician awareness of the warning signs, diagnostic options and
      potential complications of ATIL. In this patient, adalimumab was discontinued and
      treatment was started, leading to improvement in the patient's status. 

PMID- 25756477
TI  - Granulomatous pigmented purpuric dermatosis: an unusual variant associated with
      hyperlipidemia.
AB  - Granulomatous pigmented purpuric dermatosis (PPD) is a rare subtype of pigmented
      purpuric dermatosis that is typically seen in women of Far East Asian descent on
      the distal lower extremities and feet. Granulomatous PPD is a benign condition
      that does not typically require treatment. Hyperlipidemia has been seen in over
      half of the eighteen cases reported in the literature. We report an unusual
      presentation of granulomatous PPD seen in a 71 year-old Caucasian female with
      hyperlipidemia. 

PMID- 25756478
TI  - Paraneoplastic plaque-like cutaneous mucinosis: a case report.
AB  - Plaque-like cutaneous mucinosis (PCM) is a rare disorder of dermal mucin
      deposition. Some patients with PCM will be found to have an associated
      malignancy. We report the case of a 72-year-old man presenting with new onset
      pruritic, waxy-appearing erythematous and skin-colored papules and nodules
      coalescing into plaques on his shoulder, scalp, and forehead. Skin biopsy
      revealed cutaneous mucinosis. Despite conservative treatment, his skin lesions
      progressed, and he was found to have an occult malignancy of pancreatobiliary
      origin. After several months of chemotherapy, his skin lesions showed progressive
      improvement. To our knowledge, this is the third reported case of paraneoplastic
      PCM and the first reported to occur in association with underlying adenocarcinoma
      of pancreatobiliary origin. PCM may occasionally represent a paraneoplastic
      dermatosis. This case highlights the importance of a search for occult malignancy
      in such patients. 

PMID- 25756479
TI  - Linear syringocystadenoma papilliferum on female breast: a rare appendageal
      tumour on an uncommon location.
AB  - Syringocystadenoma papilliferum is a rare benign adnexal tumor commonly located
      on the head and neck region and is usually associated with a nevus sebaceous.
      Linear lesions are uncommon and lesions on the breast are extremely rare. We
      report here a case of linear SCAP occurring de novo on the left breast of a 35
      year-old healthy woman. Histopathology showed the characteristic papillary
      projections lined by double layer of cells inside epidermal invaginations. 

PMID- 25756480
TI  - Cutaneous metastasis of papillary thyroid carcinoma to the neck: a case report
      and review of the literature.
AB  - Papillary thyroid carcinoma, the most common subtype of thyroid malignancy,
      rarely presents with cutaneous metastatic spread. Despite metastatic cutaneous
      lesions presenting as slow and indolent growing nodules of the head and neck,
      such lesions most frequently appear in the setting of diffuse and dramatic
      metastatic disease and a bleak prognosis. Given the rarity of these metastatic
      lesions, the diagnosis may be delayed, and often the initial diagnosis is
      incorrect. Several case reports have been published in the literature noting
      unusual or interesting presentations of thyroid carcinoma with cutaneous
      metastasis. Here we present a classic case of a patient with a prior diagnosis of
      thyroid carcinoma presenting with a slowly growing ulcerated lesion on the neck
      nine years after partial thyroidectomy and characteristic histopathology on
      microscopic examination. Furthermore we review the literature regarding papillary
      thyroid carcinoma with cutaneous metastasis and the diagnostic challenge these
      lesions present to practitioners. 

PMID- 25756481
TI  - Cryotherapy-induced milia en plaque: case report and literature review.
AB  - BACKGROUND: Cryotherapy-induced milia is a rarely described cutaneous reaction
      that may occur in patients who have received cryotherapy with liquid nitrogen.
      Cryotherapy-induced milia is characterized by 1-2 millimeter white dermal cysts
      that develop at the healed cryotherapy site. Milia en plaque, an erythematous
      plaque containing numerous milia, has not previously been described following
      treatment of a skin lesion with liquid nitrogen cryotherapy. PURPOSE: We describe
      a man who developed cryotherapy-induced milia en plaque after receiving
      cryotherapy to his dorsal hand for the treatment of an actinic keratosis. We also
      summarize the potential complications of cryotherapy, the differential diagnosis
      of milia en plaque, and therapeutic interventions for this lesion. MATERIALS AND
      METHODS: The features of a man with cryotherapy-induced milia en plaque are
      presented. Using PubMed, the following terms were searched and relevant citations
      assessed: cryosurgery, cryotherapy, hypothermia, milia, milia en plaque, and
      Wolf's isotopic response. In addition, the literature on cryotherapy-induced
      milia and cryotherapy-induced milia en plaque is reviewed. RESULTS: Our patient
      developed cryotherapy-induced milia en plaque shortly after his cryotherapy site
      had healed. Some of the asymptomatic cystic dermal lesions had spontaneously
      resolved when a lesional biopsy was performed to confirm the diagnosis. The
      diagnosis, natural course, and potential treatments were discussed with the
      patient. Subsequent management was to observe the area; at follow-up examination,
      the remainder of the milia had also spontaneously resolved. CONCLUSION:
      Cryotherapy-induced milia is a benign condition characterized by the development
      of small white dermal cystic lesions that develop at a healed liquid nitrogen
      cryotherapy site. The lesions may appear individually or as milia en plaque.
      While the mechanism of pathogenesis is unknown, we postulate that the condition
      is an example of Wolf's isotopic response, in which a new, unrelated skin disease
      develops at the site of a previously healed dermatosis - in this circumstance,
      following cryotherapy which created an immune compromised zone. The diagnosis of
      milia en plaque can usually be established by clinical presentation; if
      necessary, a biopsy can be performed to provide pathologic confirmation of the
      suspected diagnosis. Treatment options include manual extraction, topical
      retinoids, or observation. Similar to our patient, the milia may resolve
      spontaneously.

PMID- 25756482
TI  - Home ultraviolet light therapy for psoriasis: why patients choose other options.
AB  - BACKGROUND: Psoriasis is a common inflammatory skin condition for which office
      based and home phototherapy are safe and effective treatments. However, patients
      who are prescribed home phototherapy devices often choose other treatment
      options. OBJECTIVE: To determine the reasons why patients do not purchase a home
      phototherapy device after it has been recommended and prescribed by their
      physician. METHODS: Patients who were written a prescription for a home
      phototherapy device but did not fill the prescription were identified and
      contacted by the National Biological Corporation to participate in a telephone
      survey consisting of 4 questions regarding why they did not pursue a prescribed
      home ultraviolet device and how they were currently treating their psoriasis.
      RESULTS: The most common reason for not obtaining the prescribed home
      phototherapy device was using a biologic agent (31%). The second and third most
      frequently reported reasons were "cost share too high" and "insurance will not
      cover" (18% and 17%, respectively), together accounting for 35%. LIMITATIONS: The
      reason why patients were prescribed biologics while having an unfilled home
      phototherapy device prescription was not obtained. CONCLUSIONS: Out of pocket
      cost is a significant barrier to home phototherapy, even to patients who are well
      insured.

PMID- 25756483
TI  - Update on mobile applications in dermatology.
AB  - BACKGROUND: As the use of mobile devices surpasses that of personal computers,
      medical applications increasingly provide easy access to a diverse range of
      health care resources. PURPOSE: To analyze changes in the number of dermatologic
      mobile applications since 2012. METHODS: We examined five mobile platforms
      (Apple, Android, Windows, Nokia, and Blackberry) for dermatology-related
      diagnoses applications. The apps were categorized by purpose, cost, and target
      audience. RESULTS: A total of 365 dermatologic mobile applications were analyzed
      with 225 new mobile applications found since 2012. Since the last query, there
      was a decrease in market share of reference materials (26.6% in 2012 to 15.9% in
      2014) and self-surveillance/diagnosis applications (17.9% in 2012 to 12.9% in
      2014) while teledermatology apps increased from 3.5% of total apps in 2012 to 9%
      in 2014. CONCLUSIONS: Dermatology apps continue to proliferate with minimal
      regulation. As technology continues to advance and physicians have greater access
      to mobile- health information, novel advancements in diagnosis may lead to more
      time-and-location-flexible patient care.

PMID- 25756484
TI  - Is the duration of skin disease visits decreasing in the United States?
AB  - BACKGROUND: Changes in the practice of medicine may be affecting how much time
      physicians spend with their patients. Economic pressures in some health systems
      may limit how much time patients spend with doctors. Inefficiencies associated
      with the use of EMR potentially could lengthen the duration of office visits.
      OBJECTIVE: To assess trends in the duration of skin disease visits over the last
      two decades. METHODS: Skin disease visits were selected from the 1993-2010
      National Ambulatory Medical Care Survey. Changes in overall number of visits per
      dermatologist, variation in visit duration, and differences by specialty in visit
      duration were assessed. RESULTS: The mean duration of skin disease visits
      increased over time for both dermatologists (beta=0.24 minutes) and
      nondermatologists (beta=0.19, both P<0.0001). For visits with a sole diagnosis of
      skin disease, dermatologist visits were shorter (14.7 minutes) than
      nondermatologist visits (16.4 minutes, P<0.0001). Visits for unspecified warts,
      atopic dermatitis, unspecified dermatitis, and acne grew significantly longer
      over time. In a multivariate analysis, older age, later year, nondermatology
      specialty, new patient status, procedure performed, private insurance, no
      physician extender involvement, and electronic medical records were associated
      with longer visit duration. LIMITATIONS: The data are not informative about the
      quality of the time physicians spend with patients. CONCLUSIONS: Economic
      pressures have, so far, not reduced the average time physicians spend in direct
      contact with patients.

PMID- 25756485
TI  - Whitish oral lesions in a heavy pipe smoker.
AB  - Classically known as the "Great Imitator", the diagnosis of syphilis continues to
      be an enormous challenge. We describe a case of isolated oral lesions as the sole
      presentation of secondary syphilis and only clinical clue to previously
      undiagnosed human immunodeficiency virus infection. The current increase in new
      cases of syphilis is leading to reemergence of forgotten old scenarios, which
      physicians should bear in mind within the differential diagnosis of their daily
      practice. 

PMID- 25756486
TI  - Dermoscopy of acral angioma serpiginosum.
AB  - Angioma serpiginosum (AS) is an unusual vascular disorder that typically affects
      female patients, begins in childhood and stabilizes in adulthood and not
      frequently involve acral skin. We herein present a 13 year-old girl with an
      asymptomatic erythematous punctuate first noticed on the right palm three years
      ago, with a proximal serpiginous progression up to the forearm. On examination
      there was a nonblanching erythematous punctuate on the palm and the inner aspect
      of right hand and forearm. Dermoscopy showed an erythematous parallel ridge
      pattern with some red globules and dots spreading on a linear arrangement, and
      the acrosyringia openings were not affected. Histopathological study showed
      dilated capillaries in the dermal papillae. This feature is consistent with
      angioma serpiginosum (AS). To the best of our knowledge, this is the first report
      that shows a dermoscopic image of a palmar AS. The dermoscopic pattern described
      in this case could aid in the diagnosis of AS and could add a value in the
      differential diagnosis with vascular lesions on acral skin. 

PMID- 25756487
TI  - Digitial endochondroma.
AB  - A patient with Ollier disease presenting with onycholysis and nail dystrophy
      related to a subungual enchondroma is presented.

PMID- 25756488
TI  - Gluteal silicone injections leading to extensive filler migration with induration
      and arthralgia.
AB  - Silicone injections have been used for cosmetic soft tissue augmentation for over
      five decades with documented consequences both systemic and dermatologic. We
      present a case of extensive filler migration causing bilateral lower extremity
      woody induration in a 53 year old Hispanic woman. She presented with a multi-year
      history of progressive joint stiffening at the knees, accompanied by induration
      and pain of the bilateral lower extremities. The patient had received two
      injections of an unknown substance placed into her bilateral gluteals 11 years
      prior. MRI indicated an infiltrative process of both lower extremities and
      pathology was consistent with migration of injected tissue augmentation material,
      most likely silicone. Due to the extent of involvement the patient was started on
      a trial of doxycycline 100 mg PO BID. 

PMID- 25756489
TI  - News reports: update on buying indoor UV tanning with university debit cards.
AB  - BACKGROUND & OBJECTIVE: Indoor tanning by adults under 35 years of age increases
      the risk of developing melanoma 59% to 75%. Cost is a major barrier limiting
      young adults from purchasing indoor tanning services. Our recent study by Boyers
      et al determined that 18 of 96 major universities, all in the eastern and
      southern United States, had university-sponsored debit cards with indoor tanning
      affiliations. These debit cards, which conveniently link with student
      identification (ID) cards, help with student living expenses and are often loaded
      with money by parents. By creating agreements with indoor tanning salon vendors,
      universities are endorsing a World Health Organization class I carcinogen. To
      expand the results of our previous study, we broadened our search to further
      assess universities in the western United States as well as Australia, New
      Zealand, Ireland, Canada, and the United Kingdom. METHODS: Using
      www.collegeboard.edu, we identified the 4 largest residential colleges in
      Arizona, California, Colorado, Idaho, Montana, Nevada, New Mexico, Oregon, Utah,
      Washington, and Wyoming. Additionally, we investigated the top international
      universities, utilizing www.topuniversities.com. Internet searches, phone calls,
      and email correspondence were used to determine if an institution had a student
      ID-linked debit card. Universities with affiliations to bank debit cards and
      cards that could only be used on campus were excluded. RESULTS: In the western
      United States, indoor tanning merchants were affiliated with University of
      Arizona, Embry-Riddle Aeronautical University: Prescott Campus, and the
      University of Denver student debit cards. Of the original 18 schools with
      affiliations according to the Boyers et al study, 2 universities no longer have
      agreements and 5 created agreements with additional tanning salons. Of 45
      universities examined in our international search, no debit cards were discovered
      for off-campus purchases. Therefore, the concerning issue of university
      associations with tanning salons appears to be solely a domestic problem.
      CONCLUSIONS: Our findings indicate that the formation of financial agreements
      between universities and tanning salons is an ever-present and growing problem in
      the United States. Since Boyers et al, we have engaged in outreach efforts with
      alumni, faculty, administration, and local university cancer centers to terminate
      university ties with tanning salon vendors. Further advocacy efforts are critical
      to combat this dangerous association, reduce the frequency of skin cancer, and
      protect the health of young adults.

PMID- 25756490
TI  - Sweet syndrome associated with interferon.
AB  - Although still very rare, drug-related cases of Sweet's syndrome have been
      reported. The more frequent associated medications with drug induced Sweet's
      syndrome was: tetracyclines, trimethoprim-sulphamethaxazol, azatioprine, all
      trans retinoic acid, nitrofurantoin, granulocyte colony-stimulating factor,
      hydralazine, tripharil, lithium, oral contraceptives, furosemide, celecoxib and
      azathioprine. We only found one case of drug-induced Sweet's syndrome secondary
      to pegylated interferon-alpha in combination with ribavirin reported in
      literature. To our knowledge, this one is the first reported case of Sweet's
      syndrome in association with interferon beta 1-b therapy.Also, we would like to
      remark the atypical localization of the lesions in our patient, with a unilateral
      predominance on the left lower extremity and a very severe pain.

PMID- 25756491
TI  - Patient perspectives on low level light therapy and laser therapies for rosacea
      associated persistent facial redness.
AB  - INTRODUCTION: There are no definitive treatments of facial redness for rosacea.
      All treatments aim to alleviate symptoms. Patients' perspectives of two emerging
      modalities, Low level light therapy and laser treatments are not well
      characterized. The purpose is to further understand rosacea patients unmet needs
      about these modalities, Methods: The publicly accessible, online rosacea forum
      was accessed at august 2013. Stratified random sampling method has done to
      identify a 10% sample of total 27,051 posts. The Posts were published in the
      "Laser and IPL therapy" and "Low level light therapy" forums were qualitatively
      analyzed. RESULTS: Patients discussed a variety of topics, but most commonly
      discussed effectiveness (34.2%), treatment education (19.3%), and adverse effects
      (18%). Relationship with the health care provider (9.9%), cost (8.1%), execution
      of treatments (8.1%) and convenience of treatments (2.5%) were less commonly
      discussed, but contributed to patients' decisions about utilizing laser and light
      therapies. CONCLUSIONS: Online forums are utilized to fulfill patients' desire
      for educational, empathic and collaborative relationship. Patients' adherence to
      laser and light therapies will likely increase if costs are reduced, reduction in
      redness is consistent with their expectations, and if physicians empower them
      through education on device choices and managing adverse effects.

PMID- 25756492
TI  - Participant satisfaction with appearance-based versus health-based educational
      videos promoting sunscreen use: a randomized controlled trial.
AB  - BACKGROUND: Increasing participant satisfaction with health interventions can
      improve compliance with recommended health behaviors and lead to better health
      outcomes. However, factors that influence participant satisfaction have not been
      well studied in dermatology-specific behavioral health interventions. We sought
      to assess participant satisfaction of either an appearance-based educational
      video or a health-based educational video promoting sunscreen use along
      dimensions of usefulness of educational content, message appeal, and presentation
      quality. METHODS: In a randomized controlled trial, participants were randomized
      1:1 to view an appearance-based video or a health-based video. After six weeks,
      participant satisfaction with the educational videos was assessed. RESULTS: Fifty
      high school students were enrolled and completed the study. Participant
      satisfaction ratings were assessed using a pre-tested 10-point assessment scale.
      The participants rated the usefulness of the appearance-based video (8.1 +/- 1.2)
      significantly higher than the health-based video (6.4 +/- 1.4, p<0.001). The
      message appeal of the appearance-based video (8.3 +/- 1.0) was also significantly
      higher than the health-based video (6.6 +/- 1.6, p<0.001). The presentation
      quality rating was similar between the appearance-based video (7.8 +/- 1.3) and
      the health-based video (8.1 +/- 1.3), p=0.676. CONCLUSIONS: Adolescents rated the
      appearance-based video higher than the health-based video in terms of usefulness
      of educational content and message appeal.

PMID- 25756493
TI  - Extensive hidradenitis suppurativa (HS) Hurly stage III disease treated with
      intravenous (IV) linezolid and meropenem with rapid remission.
AB  - A 57-year-old woman with Hurley Stage 3 hidradenitis suppurativa (HS) and
      multiple co-morbidities is presented. She had failed multiple antibiotic
      therapies and etanercept. She had end stage renal disease and was on dialysis.
      Her HS was put into remission with one month of daily IV treatment with 1.2 grams
      linezolid and 1 gram of meropenem, administered daily through her dialysis shunt.
      Unfortunately, her disease flared again two weeks after the cessation of the IV
      treatment. Nevertheless, more conventional therapy was then able to maintain her
      disease at a level that was significantly improved over baseline prior to the IV
      treatment. This case highlights above all a primary etiology of HS is stimulus of
      immune system's over-reaction in HS to the bacterial microbiome. If antibiotics
      are administered to a patient with stage 3 HS powerful enough to wipe out the
      bacterial biome, the immune system having no target retreats, permanent scarring
      in its wake and retreats to a certain but hardly permanent normalcy. 

PMID- 25756494
TI  - Going mobile: non-cell-autonomous small RNAs shape the genetic landscape of
      plants.
AB  - RNA silencing is a form of genetic regulation, which is conserved across
      eukaryotes and has wide ranging biological functions. Recently, there has been a
      growing appreciation for the importance of mobility in RNA silencing pathways,
      particularly in plants. Moreover, in addition to the importance for mobile RNA
      silencing in an evolutionary context, the potential for utilizing mobile short
      silencing RNAs in biotechnological applications is becoming apparent. This review
      aims to set current knowledge of this topic in a historical context and provides
      examples to illustrate the importance of mobile RNA silencing in both natural and
      artificially engineered systems in plants. 

PMID- 25756495
TI  - Genetic analysis and major quantitative trait locus mapping of leaf widths at
      different positions in multiple populations.
AB  - BACKGROUND: Leaf width is an important agricultural trait in maize. Leaf
      development is dependent on cell proliferation and expansion, and these processes
      exhibit polarity with respect to the longitudinal and transverse axes of the
      leaf. However, the molecular mechanism of the genetic control of seed vigor
      remains unknown in maize, and a better understanding of this mechanism is
      required. METHODOLOGY/PRINCIPAL FINDINGS: To reveal the genetic architecture of
      leaf width, a comprehensive evaluation using four RIL populations was performed,
      followed by a meta-analysis. Forty-six QTLs associated with the widths of leaves
      at different positions above the uppermost ear were detected in the four RIL
      populations in three environments. The individual effects of the QTLs ranged from
      4.33% to 18.01% of the observed phenotypic variation, with 14 QTLs showing
      effects of over 10%. We identified three common QTLs associated with leaf width
      at all of the examined positions, in addition to one common QTL associated with
      leaf width at three of the positions and six common QTLs associated with leaf
      width at two of the positions. The results indicate that leaf width at different
      leaf positions may be affected by one QTL or several of the same QTLs. Such
      traits may also be regulated by many different QTLs. Thirty-one of the forty-six
      initial QTLs were integrated into eight mQTLs through a meta-analysis, and 10 of
      the 14 initial QTLs presenting an R2>10% were integrated into six mQTLs.
      CONCLUSIONS/SIGNIFICANCE: mQTL1-2, mQTL3-1, mQTL7, and mQTL8 were composed of the
      initial QTLs showing an R2>10% and included four to six of the initial QTLs that
      were associated with two to four positions in a single population. Therefore,
      these four chromosome regions may be hot spots for important QTLs for these
      traits. Thus, they warrant further studies and may be useful for marker-assisted
      breeding.

PMID- 25756496
TI  - Oxidative degradation of nalidixic acid by nano-magnetite via Fe2+/O2-mediated
      reactions.
AB  - Organic pollution has become a critical issue worldwide due to the increasing
      input and persistence of organic compounds in the environment. Iron minerals are
      potentially able to degrade efficiently organic pollutants sorbed to their
      surfaces via oxidative or reductive transformation processes. Here, we explored
      the oxidative capacity of nano-magnetite (Fe3O4) having ~ 12 nm particle size, to
      promote heterogeneous Fenton-like reactions for the removal of nalidixic acid
      (NAL), a recalcitrant quinolone antibacterial agent. Results show that NAL was
      adsorbed at the surface of magnetite and was efficiently degraded under oxic
      conditions. Nearly 60% of this organic contaminant was eliminated after 30 min
      exposure to air bubbling in solution in the presence of an excess of nano
      magnetite. X-ray diffraction (XRD) and Fe K-edge X-ray absorption spectroscopy
      (XANES and EXAFS) showed a partial oxidation of magnetite to maghemite during the
      reaction, and four byproducts of NAL were identified by liquid chromatography
      mass spectroscopy (UHPLC-MS/MS). We also provide evidence that hydroxyl radicals
      (HO(*)) were involved in the oxidative degradation of NAL, as indicated by the
      quenching of the degradation reaction in the presence of ethanol. This study
      points out the promising potentialities of mixed valence iron oxides for the
      treatment of soils and wastewater contaminated by organic pollutants.

PMID- 25756497
TI  - Late effects of adjuvant chemotherapy for breast cancer on fine motor function.
AB  - BACKGROUND: Adjuvant chemotherapy for breast cancer has been associated with
      deterioration of fine motor skill. Which aspects of motor performance are
      underlying this problem is unclear but important because manual motor
      deterioration could affect quality of life. The current study aims to investigate
      late effects of adjuvant chemotherapy for breast cancer on fine motor function,
      using both speed and accuracy measures. METHOD: We compared fine motor function
      of 174 women who had received adjuvant Cyclophosphamide Methotrexate 5
      Fluorouracil chemotherapy for breast cancer on average 20 years ago with that of
      a population sample of 195 women without a history of cancer. Fine motor function
      was measured with the Purdue Pegboard Test and the Archimedes spiral test.
      RESULTS: The group of chemotherapy-exposed breast cancer survivors was slower in
      drawing an Archimedes spiral than the reference group. Furthermore, in the
      chemotherapy-exposed subjects, we found that older age is related to more
      crossings of the spiral template, more return movements, and more deviations from
      the template. Such relationships were not observed within the reference group. No
      significant between-group differences were found for any of the Purdue Pegboard
      measures. CONCLUSIONS: Compared with a population-based reference group,
      Cyclophosphamide Methotrexate 5-Fluorouracil chemotherapy-exposed breast cancer
      survivors demonstrated motor slowing while drawing an Archimedes spiral, on
      average 20 years after completion of primary treatment. Furthermore, the
      Archimedes spiral test is a more sensitive measure than the Purdue Pegboard Test
      to assess fine manual motor performance in long-term breast cancer survivors
      following chemotherapy.

PMID- 25756499
TI  - Improving the implementation of NICE public health workplace guidance: an
      evaluation of the effectiveness of action-planning workshops in NHS trusts in
      England.
AB  - RATIONALE, AIMS AND OBJECTIVES: There is evidence that health and well-being of
      the National Health Service (NHS) workforce affects organizational and patient
      outcomes. A Cochrane review of the effectiveness of clinical audit to improve
      quality of care has shown great variation between studies, depending on the
      design and intensity of support offered. This study evaluates the effectiveness
      of an organizational audit methodology with (1) action-planning workshops and
      follow-up and (2) audit feedback alone, to support the implementation of the
      National Institute for Health and Care Excellence (NICE) workplace guidance.
      METHODS: Two rounds of audit using a self-administered online questionnaire were
      conducted. An overall implementation score was devised for each trust. Following
      round 1, interviews were conducted with a cohort of trusts with high scores. The
      interviews used a theory-based framework to identify predictors of and barriers
      to successful implementation. From this, the content for action-planning
      workshops was devised and workshops held with lower scoring trusts. The remaining
      trusts received only written feedback on their audit results. Changes in the
      implementation score between rounds 1 and 2 were compared within and between
      cohorts. RESULTS: The median improvement in scores between rounds 1 and 2 was
      statistically significant except where baseline score was high. The improvement
      for trusts who received workshops was very much better than those who did not (P
      < 0.001). This difference remained after adjustment using stratification by
      baseline score (P = 0.001). CONCLUSIONS: Audit, combined with action-planning
      workshops and follow-up, appears to be more effective in improving implementation
      of NICE workplace health and well-being guidance than audit with feedback alone.

PMID- 25756498
TI  - Point-of-care CD4 testing to inform selection of antiretroviral medications in
      south african antenatal clinics: a cost-effectiveness analysis.
AB  - BACKGROUND: Many prevention of mother-to-child HIV transmission (PMTCT) programs
      currently prioritize antiretroviral therapy (ART) for women with advanced HIV.
      Point-of-care (POC) CD4 assays may expedite the selection of three-drug ART
      instead of zidovudine, but are costlier than traditional laboratory assays.
      METHODS: We used validated models of HIV infection to simulate pregnant, HIV
      infected women (mean age 26 years, gestational age 26 weeks) in a general
      antenatal clinic in South Africa, and their infants. We examined two strategies
      for CD4 testing after HIV diagnosis: laboratory (test rate: 96%, result-return
      rate: 87%, cost: $14) and POC (test rate: 99%, result-return rate: 95%, cost:
      $26). We modeled South African PMTCT guidelines during the study period (WHO
      "Option A"): antenatal zidovudine (CD4 <=350/MUL) or ART (CD4>350/MUL). Outcomes
      included MTCT risk at weaning (age 6 months), maternal and pediatric life
      expectancy (LE), maternal and pediatric lifetime healthcare costs (2013 USD), and
      cost-effectiveness ($/life-year saved). RESULTS: In the base case, laboratory led
      to projected MTCT risks of 5.7%, undiscounted pediatric LE of 53.2 years, and
      undiscounted PMTCT plus pediatric lifetime costs of $1,070/infant. POC led to
      lower modeled MTCT risk (5.3%), greater pediatric LE (53.4 years) and lower PMTCT
      plus pediatric lifetime costs ($1,040/infant). Maternal outcomes following
      laboratory were similar to POC (LE: 21.2 years; lifetime costs: $23,860/person).
      Compared to laboratory, POC improved clinical outcomes and reduced healthcare
      costs. CONCLUSIONS: In antenatal clinics implementing Option A, the higher
      initial cost of a one-time POC CD4 assay will be offset by cost-savings from
      prevention of pediatric HIV infection.

PMID- 25756500
TI  - Inhibition of Bcl-2 sensitizes mitochondrial permeability transition pore (MPTP)
      opening in ischemia-damaged mitochondria.
AB  - BACKGROUND: Mitochondria are critical to cardiac injury during reperfusion as a
      result of damage sustained during ischemia, including the loss of bcl-2. We asked
      if bcl-2 depletion not only leads to selective permeation of the outer
      mitochondrial membrane (MOMP) favoring cytochrome c release and programmed cell
      death, but also favors opening of the mitochondrial permeability transition pore
      (MPTP). An increase in MPTP susceptibility would support a role for bcl-2
      depletion mediated cell death in the calcium overload setting of early
      reperfusion via MPTP as well as later in reperfusion via MOMP as myocardial
      calcium content normalizes. METHODS: Calcium retention capacity (CRC) was used to
      reflect the sensitivity of the MPTP opening in isolated cardiac mitochondria. To
      study the relationship between bcl-2 inhibition and MPTP opening, mitochondria
      were incubated with a bcl-2 inhibitor (HA14-1) and CRC measured. The contribution
      of preserved bcl-2 content to MPTP opening following ischemia-reperfusion was
      explored using transgenic bcl-2 overexpressed mice. RESULTS: CRC was decreased in
      mitochondria following reperfusion compared to ischemia alone, indicating that
      reperfusion further sensitizes to MPTP opening. Incubation of ischemia-damaged
      mitochondria with increasing HA14-1concentrations increased calcium-stimulated
      MPTP opening, supporting that functional inhibition of bcl-2 during simulated
      reperfusion favors MPTP opening. Moreover, HA14-1 sensitivity was increased by
      ischemia compared to non-ischemic controls. Overexpression of bcl-2 attenuated
      MPTP opening in following ischemia-reperfusion. HA14-1 inhibition also increased
      the permeability of the outer membrane in the absence of exogenous calcium,
      indicating that bcl-2 inhibition favors MOMP when calcium is low. CONCLUSIONS:
      The depletion and functional inhibition of bcl-2 contributes to cardiac injury by
      increasing susceptibility to MPTP opening in high calcium environments and MOMP
      in the absence of calcium overload. Thus, ischemia-damaged mitochondria with
      decreased bcl-2 content are susceptible to MPTP opening in early reperfusion and
      MOMP later in reperfusion when cytosolic calcium has normalized.

PMID- 25756501
TI  - Randomized controlled field trial to assess the immunogenicity and safety of rift
      valley fever clone 13 vaccine in livestock.
AB  - BACKGROUND: Although livestock vaccination is effective in preventing Rift Valley
      fever (RVF) epidemics, there are concerns about safety and effectiveness of the
      only commercially available RVF Smithburn vaccine. We conducted a randomized
      controlled field trial to evaluate the immunogenicity and safety of the new RVF
      Clone 13 vaccine, recently registered in South Africa. METHODS: In a blinded
      randomized controlled field trial, 404 animals (85 cattle, 168 sheep, and 151
      goats) in three farms in Kenya were divided into three groups. Group A included
      males and non-pregnant females that were randomized and assigned to two groups;
      one vaccinated with RVF Clone 13 and the other given placebo. Groups B included
      animals in 1st half of pregnancy, and group C animals in 2nd half of pregnancy,
      which were also randomized and either vaccinated and given placebo. Animals were
      monitored for one year and virus antibodies titers assessed on days 14, 28, 56,
      183 and 365. RESULTS: In vaccinated goats (N = 72), 72% developed anti-RVF virus
      IgM antibodies and 97% neutralizing IgG antibodies. In vaccinated sheep (N = 77),
      84% developed IgM and 91% neutralizing IgG antibodies. Vaccinated cattle (N = 42)
      did not develop IgM antibodies but 67% developed neutralizing IgG antibodies. At
      day 14 post-vaccination, the odds of being seropositive for IgG in the vaccine
      group was 3.6 (95% CI, 1.5 - 9.2) in cattle, 90.0 (95% CI, 25.1 - 579.2) in
      goats, and 40.0 (95% CI, 16.5 - 110.5) in sheep. Abortion was observed in one
      vaccinated goat but histopathologic analysis did not indicate RVF virus
      infection. There was no evidence of teratogenicity in vaccinated or placebo
      animals. CONCLUSIONS: The results suggest RVF Clone 13 vaccine is safe to use and
      has high (>90%) immunogenicity in sheep and goats but moderate (> 65%)
      immunogenicity in cattle.

PMID- 25756502
TI  - Irreversible endo-selective diels-alder reactions of substituted alkoxyfurans: a
      general synthesis of endo-cantharimides.
AB  - The [4+2] cycloaddition of 3-alkoxyfurans with N-substituted maleimides provides
      the first general route for preparing endo-cantharimides. Unlike the
      corresponding reaction with 3H furans, the reaction can tolerate a broad range of
      2-substitued furans including alkyl, aromatic, and heteroaromatic groups. The
      cycloaddition products were converted into a range of cantharimide products with
      promising lead-like properties for medicinal chemistry programs. Furthermore, the
      electron-rich furans are shown to react with a variety of alternative dienophiles
      to generate 7-oxabicyclo[2.2.1]heptane derivatives under mild conditions. DFT
      calculations have been performed to rationalize the activation effect of the 3
      alkoxy group on a furan Diels-Alder reaction. 

PMID- 25756503
TI  - Antibacterial Polyketide Heterodimers from Pyrenacantha kaurabassana Tubers.
AB  - Two heterodimers comprising anthraquinone and methylbenzoisocoumarin moieties (1
      and 2) were isolated, together with emodin and physcion from the tubers of
      Pyrenacantha kaurabassana. The structures of 1 and 2 were established by NMR
      spectroscopy, including the analysis of a 2D INADEQUATE spectrum. On the basis of
      the data obtained, the structures that were previously proposed in the literature
      for these compounds were revised. Compounds 1 and 2 showed antibacterial activity
      against three different strains of Staphylococcus aureus. Compound 2 also showed
      bactericidal activity against Helicobacter pylori. 

PMID- 25756504
TI  - The daphniphyllum alkaloids: total synthesis of (-)-calyciphylline N.
AB  - Presented here is a full account on the development of a strategy culminating in
      the first total synthesis of the architecturally complex daphniphyllum alkaloid,
      (-)-calyciphylline N. Highlights of the approach include a highly
      diastereoselective, intramolecular Diels-Alder reaction of a silicon-tethered
      acrylate; an efficient Stille carbonylation of a sterically encumbered vinyl
      triflate; a one-pot Nazarov cyclization/proto-desilylation sequence; and the
      chemoselective hydrogenation of a fully substituted diene ester. 

PMID- 25756505
TI  - Donepezil-related intractable hiccups: a case report.
AB  - This case report describes a man with intractable hiccups probably caused by
      donepezil. The patient's symptoms were not responsive to commonly used
      medications for hiccups, but they were improved and completely relieved upon
      donepezil dose deescalation and discontinuation. We report two occasions in which
      the discontinuation of donepezil resulted in hiccup resolution and three
      occasions in which initiation of donepezil was associated with the onset of
      hiccups. This report contributes to the growing body of literature that describes
      an association between centrally acting medications and intractable hiccups. 

PMID- 25756506
TI  - Are there alternative ways to quantify the real benefit of novel agents in
      oncology? - the 'death pace'.

PMID- 25756507
TI  - Targeted PI3Kdelta inhibition by the small molecule idelalisib as a novel therapy
      in indolent non-Hodgkin lymphoma.
AB  - Indolent Non-Hodgkin Lymphomas (iNHL) are typically B-cell malignancies and are
      incurable with current standard approaches. Thus, there is a demand for novel
      agents specific for this group of disorders. In a phase II study published by
      Gopal et al. in the New England Journal of Medicine, idelalisib, a small molecule
      inhibitor of PI3Kdelta that was FDA approved in July of 2014, was shown to be
      effective when combined with rituximab in patients who cannot tolerate
      chemotherapy and as last line therapy in patients with iNHL refractory to 2 prior
      systemic therapies. Idelalisib demonstrated tolerable diarrhea, fatigue, nausea,
      pyrexia, and cough. While this novel agent is a clinically significant addition
      to the iNHL arsenal, further research is needed to determine its most appropriate
      place in iNHL therapy. 

PMID- 25756508
TI  - Dexamethasone may be the most efficacious corticosteroid for use as monotherapy
      in castration-resistant prostate cancer.
AB  - Corticosteroids have been used in the therapy for castration-resistant prostate
      cancer (CRPC) for decades, both as monotherapy and in combination with additional
      agents. In this article the authors report the results of a phase II trial of
      dexamethasone versus prednisolone as monotherapy for CRPC. The study suggests
      improved PSA and radiographic response rates as well as improved time to PSA
      progression for dexamethasone over prednisolone therapy; however the differences
      only trend toward statistical significance. Nonetheless, in light of these data,
      when treating patients with corticosteroid monotherapy for CRPC it may be prudent
      to consider using daily dexamethasone over prednisone/prednisolone. 

PMID- 25756509
TI  - MiR-1204 sensitizes nasopharyngeal carcinoma cells to paclitaxel both in vitro
      and in vivo.
AB  - Nasopharyngeal carcinoma (NPC) is an endemic tumor with a relatively high
      incidence in Southern China and Southeast Asia. Paclitaxel combination
      chemotherapy has been used for treatment of advanced NPC. However, treatment
      failure often occurs due to development of acquired paclitaxel resistance. In
      this study, we first established a paclitaxel-resistant CNE-1/Taxol, HNE-2/Taxol
      and 5-8F/Taxol cell sublines by treating the parental CNE-1, HNE-2 and 5-8F cells
      with increasing doses of paclitaxel for about 5 months, respectively. Then,
      microRNA arrays were used to screen differentially expressed miRNAs between the
      CNE-1/Taxol cells and the parental CNE-1 cells. We found 13 differentially
      expressed miRNAs, of which miR-1204 was significantly downregulated in the
      paclitaxel-resistant CNE-1/Taxol cells. We restored miR-1204 expression in the
      CNE-1/Taxol, HNE-2/Taxol and 5-8F/Taxol cells and found that restoration of miR
      1204 re-sensitized the paclitaxel-resistant CNE-1/Taxol, HNE-2/Taxol and 5
      8F/Taxol cells to paclitaxel both in vitro. Finally, we demonstrated that
      restoration of miR-1204 in significantly inhibits tumor growth in vivo. Thus, our
      study provides important information for the development of targeted gene therapy
      for reversing paclitaxel resistance in NPC. 

PMID- 25756510
TI  - EGFR signaling defines Mcl-1 survival dependency in neuroblastoma.
AB  - The pediatric solid tumor neuroblastoma (NB) often depends on the anti-apoptotic
      protein, Mcl(-)1, for survival through Mcl(-)1 sequestration of pro-apoptotic
      Bim. High affinity Mcl(-)1 inhibitors currently do not exist such that novel
      methods to inhibit Mcl(-)1 clinically are in high demand. Receptor tyrosine
      kinases (RTK) regulate Mcl(-)1 in many cancers and play a role in NB survival,
      yet how they regulate Bcl(-)2 family interactions in NB is unknown. We found that
      NB cell lines derived to resist the Bcl(-)2/-xl/-w antagonist, ABT-737, acquire a
      dependence on Mcl(-)1 and show increased expression and activation of the RTK,
      EGFR. Mcl(-)1 dependent NB cell lines derived at diagnosis and from the same
      tumor following relapse also have increased EGFR expression compared to those
      dependent on Bcl(-)2. Inhibition of EGFR by shRNA or erlotinib in Mcl(-)1
      dependent NBs disrupts Bim binding to Mcl(-)1 and enhances its affinity for Bcl(
      )2, restoring sensitivity to ABT-737 as well as cytotoxics in vitro.
      Mechanistically treatment of NBs with small molecule inhibitors of EGFR
      (erlotinib, cetuximab) and ERK (U0126) increases Noxa expression and
      dephosphorylates Bim to promote Bim binding to Bcl(-)2. Thus, EGFR regulates Mcl(
      )1 dependence in high-risk NB via ERK-mediated phosphorylation of Bim such that
      EGFR/ERK inhibition renders Mcl(-)1 dependent tumors now reliant on Bcl(-)2.
      Clinically, EGFR inhibitors are ineffective as single agent compounds in patients
      with recurrent NB, likely due to this transferred survival dependence to Bcl(-)2.
      Likewise, EGFR or ERK inhibitors warrant further testing in combination with Bcl(
      )2 antagonists in vivo as a novel future combination to overcome therapy
      resistance in the clinic. 

PMID- 25756511
TI  - NDRG2 acts as a negative regulator downstream of androgen receptor and inhibits
      the growth of androgen-dependent and castration-resistant prostate cancer.
AB  - Castration resistance is a major issue during castration therapy for prostate
      cancer and thus more effective treatment are needed for castration-resistant
      prostate cancer (CRPC). NDRG2 (N-Myc downstream regulated gene 2), a recently
      identified tumor suppressor, was previously shown to inhibit the proliferation
      and invasion of prostate cancer, but whether NDRG2 is involved in CRPC remains to
      be known. Because androgen receptor (AR) axis plays an important role in
      castration resistance, we evaluate the role of NDRG2 in AR signaling and CRPC.
      Immunohistochemistry examination of prostate cancer tissues demonstrated that the
      expression of NDRG2 is negatively correlated with that of AR and c-Myc.
      Furthermore, AR negatively regulates NDRG2, as well as alters levels of c-Myc and
      prostate specific antigen (PSA). Forced expression of NDRG2 significantly
      inhibits the in vitro growth of androgen-dependent and castration-resistant
      prostate cancer cells; this was accompanied by alterations in PSA, but not by
      those of AR and c-Myc. Finally, by mimicking castration therapy in a xenograft
      mouse model, we showed that lentivirus-mediated NDRG2 overexpression efficiently
      overcomes castration resistance. Thus, by acting as a negative regulator
      downstream of AR, NDRG2 may emerge as a potential therapy molecule for CRPC. 

PMID- 25756512
TI  - PTEN inhibits macrophage polarization from M1 to M2 through CCL2 and VEGF-A
      reduction and NHERF-1 synergism.
AB  - PTEN has been studied in several tumor models as a tumor suppressor. In this
      study, we explored the role of PTEN in the inhibition state of polarized M2
      subtype of macrophage in tumor microenvironment (TME) and the underlying
      mechanisms. To elucidate the potential effect in TME, RAW 264.7 macrophages and
      4T1 mouse breast cancer cells were co-cultured to reconstruct tumor
      microenvironment. After PTEN was down-regulated with shRNA, the expression of
      CCL2 and VEGF-A, which are definited to promote the formation of M2 macrophages,
      have a dramatically increase on the level of both gene and protein in co-cultured
      RAW 264.7 macrophages. And at the same time, NHERF-1 (Na(+)/H(+) exchanger
      regulating factor-1), another tumor suppressor has a similar tendency to PTEN. Q
      PCR and WB results suggested that PTEN and NHERF-1 were consistent with one
      another no matter at mRNA or protein level when exposed to the same stimulus.
      Coimmunoprecipitation and immunofluorescence techniques confirmed that PTEN and
      NHERF-1 were coprecipitated, and NHERF-1 protein expression was properly reduced
      with rCCL2 effect. In addition, cell immunofluorescence images revealed a
      profound transferance, in co-cultured RAW 264.7 macrophages, an up-regulation of
      NHERF-1 could promote the PTEN marked expression on the cell membrane, and this
      form for the interaction was not negligible. These observations illustrate PTEN
      with a certain synergy of NHERF-1, as well as down-regulation of CCL2 suppressing
      M2 macrophage transformation pathway. The results suggest that the activation of
      PTEN and NHERF-1 may impede the evolution of macrophages beyond the M1 into M2
      phenotype in tumor microenvironment. 

PMID- 25756513
TI  - Involvement of angiotensin II type 2 receptor (AT2R) signaling in human
      pancreatic ductal adenocarcinoma (PDAC): a novel AT2R agonist effectively
      attenuates growth of PDAC grafts in mice.
AB  - We have recently discovered the potential involvement of angiotensin II type 2
      receptor (AT2R) signaling in pancreatic cancer using AT2R deficient mice. To
      examine the involvement of AT2R expression in human PDAC, expressions of AT2R as
      well as the major angiotensin II receptor (type 1 receptor, AT1R) in human PDAC
      and adjacent normal tissue was evaluated by immunohistochemistry and real time
      PCR using surgically dissected human PDAC specimens. In immunohistochemical
      analysis, relatively strong AT1R expression was detected consistently in both
      normal pancreas and PDAC areas, whereas moderate AT2R expression was detected in
      78.5% of PDAC specimens and 100% of normal area of the pancreas. AT1R, but not
      AT2R, mRNA levels were significantly higher in the PDAC area than in the normal
      pancreas. AT2R mRNA levels showed a negative correlation trend with overall
      survival. In cell cultures, treatment with a novel AT2R agonist significantly
      attenuated both murine and human PDAC cell growth with negligible cytotoxicity in
      normal epithelial cells. In a mouse study, administrations of the AT2R agonist in
      tumor surrounding connective tissue markedly attenuated growth of only AT2R
      expressing PAN02 murine PDAC grafts in syngeneic mice. The AT2R agonist treatment
      induced apoptosis primarily in tumor cells but not in stromal cells. Taken
      together, our findings offer clinical and preclinical evidence for the
      involvement of AT2R signaling in PDAC development and pinpoint that the novel
      AT2R agonist could serve as an effective therapeutic for PDAC treatment. 

PMID- 25756514
TI  - Network-based approach to identify prognostic biomarkers for estrogen receptor
      positive breast cancer treatment with tamoxifen.
AB  - This study aims to identify effective gene networks and prognostic biomarkers
      associated with estrogen receptor positive (ER+) breast cancer using human mRNA
      studies. Weighted gene coexpression network analysis was performed with a complex
      ER+ breast cancer transcriptome to investigate the function of networks and key
      genes in the prognosis of breast cancer. We found a significant correlation of an
      expression module with distant metastasis-free survival (HR = 2.25; 95% CI .21.03
      4.88 in discovery set; HR = 1.78; 95% CI = 1.07-2.93 in validation set). This
      module contained genes enriched in the biological process of the M phase. From
      this module, we further identified and validated 5 hub genes (CDK1, DLGAP5, MELK,
      NUSAP1, and RRM2), the expression levels of which were strongly associated with
      poor survival. Highly expressed MELK indicated poor survival in luminal A and
      luminal B breast cancer molecular subtypes. This gene was also found to be
      associated with tamoxifen resistance. Results indicated that a network-based
      approach may facilitate the discovery of biomarkers for the prognosis of ER+
      breast cancer and may also be used as a basis for establishing personalized
      therapies. Nevertheless, before the application of this approach in clinical
      settings, in vivo and in vitro experiments and multi-center randomized controlled
      clinical trials are still needed. 

PMID- 25756515
TI  - Crosstalk between PI3K and Ras pathways via protein phosphatase 2A in human
      ovarian clear cell carcinoma.
AB  - Hypoxia-inducible factor-1 (HIF-1) is one of the most promising pharmacological
      targets for all types of cancer, including ovarian cancer. Ovarian clear cell
      carcinoma (OCCC) has poor prognosis because of its insensitivity to chemotherapy.
      To elucidate the characteristics of this troublesome cancer, we examined HIF
      1alpha expression under normoxia or hypoxia in various ovarian cancer cell lines.
      HIF-1alpha was highly expressed under normoxia only in RMG-1, an OCCC cell line.
      To examine whether HIF-1 is involved in the tumorigenesis of RMG-1 cells, we
      established HIF-1alpha-silenced cells, RMG-1HKD. The proliferation rate of RMG
      1HKD cells was faster than that of RMG-1 cells. Furthermore, the activity of
      MEK/ERK in the Ras pathway increased in RMG-1HKD cells, whereas that of mTOR in
      the PI3K pathway did not change. Activation of the Ras pathway was attributable
      to the increase in phosphorylated MEK via PP2A inactivation. To confirm the
      crosstalk between the PI3K and Ras pathways in vivo, RMG-1 or RMG-1HKD cells were
      transplanted into the skin of nude mice with rapamycin (an inhibitor of mTOR),
      PD98059 (an inhibitor of MEK), or both. RMG-1HKD cells showed higher sensitivity
      to PD98059 than that observed in RMD-1 cells, whereas the combination therapy
      resulted in synergistic inhibition of both cells. These findings suggest that
      inhibition of HIF-1, a downstream target of mTOR in the PI3K pathway, activates
      the Ras pathway on account of the increase in MEK phosphorylation via PP2A
      inactivation, and the crosstalk between the 2 pathways could be applied in the
      combination therapy for HIF-1-overexpressing cancers such as OCCC. 

PMID- 25756516
TI  - Calcium calmodulin dependent kinase kinase 2 - a novel therapeutic target for
      gastric adenocarcinoma.
AB  - Gastric cancer is one of the most common gastrointestinal malignancies and is
      associated with poor prognosis. Exploring alterations in the proteomic landscape
      of gastric cancer is likely to provide potential biomarkers for early detection
      and molecules for targeted therapeutic intervention. Using iTRAQ-based
      quantitative proteomic analysis, we identified 22 proteins that were
      overexpressed and 17 proteins that were downregulated in gastric tumor tissues as
      compared to the adjacent normal tissue. Calcium/calmodulin-dependent protein
      kinase kinase 2 (CAMKK2) was found to be 7-fold overexpressed in gastric tumor
      tissues. Immunohistochemical labeling of tumor tissue microarrays for validation
      of CAMKK2 overexpression revealed that it was indeed overexpressed in 94% (92 of
      98) of gastric cancer cases. Silencing of CAMKK2 using siRNA significantly
      reduced cell proliferation, colony formation and invasion of gastric cancer
      cells. Our results demonstrate that CAMKK2 signals in gastric cancer through AMPK
      activation and suggest that CAMKK2 could be a novel therapeutic target in gastric
      cancer. 

PMID- 25756517
TI  - Gefitinib, Methotrexate and Methotrexate plus 5-Fluorouracil as palliative
      treatment in recurrent head and neck squamous cell carcinoma.
AB  - This study compared the efficacy and toxicity of Gefitinib, Methotrexate and
      Methotrexate plus 5-Fluorouracil (5-FU) in patients of recurrent squamous cell
      carcinoma of head and neck (SCCHN) treated with palliative intent. Patients with
      recurrent SCCHN not amenable to curative treatment were randomly assigned to
      Gefitinib, Methotrexate or Methotrexate plus 5-FU arm. The primary end point was
      overall survival. Secondary end points of interest were objective response rate,
      toxicity and quality of life. Total 117 patients were analyzed. Median overall
      survival and objective response rates were 8.8 months, 7.8 months and 8.1 months
      and 7.7%, 5.0% and 7.9% in Gefitinib, Methotrexate and Methotrexate plus 5-FU
      arms respectively with no statistically significant difference between 3 arms.
      Gefitinib had different toxicity profile compared with other arms. Majority of
      toxicities were Grade 1 or Grade 2. Gefitinib had significant improvement in
      quality of life during initial months over Methotrexate. There was no suggestion
      that Gefitinib significantly prolonged overall survival compared with
      Methotrexate and Methotrexate plus 5-FU. However, improved Quality of Life with
      manageable toxicities was observed. 

PMID- 25756519
TI  - Protective ligand shells for luminescent SiO2-coated alloyed semiconductor
      nanocrystals.
AB  - SiO2 encapsulation of alloyed CdSeZnS nanocrystals (NCs) shows differences in
      terms of optical properties and luminescence quantum yield, depending on the
      surface composition, size, and ligand content. In this work, emphasis has been
      placed on the fine control required to obtain luminescent SiO2 encapsulated NCs
      by studying the role of oleic acid (OA), stearic acid (SA), and dodecanethiol
      (DDT) ligands on the alloyed NCs. While the use of anchored DDT molecules is
      essential to preserve the optical properties, intercalated OA and SA play a
      critical role for SiO2 nucleation, as stated by (1)H NMR (including DOSY and
      NOESY) spectroscopy. These results emphasize the importance of surface chemistry
      in NCs; it is crucial to control their reactivity, and therefore their impact, in
      different applications, from optics to biomedicine. 

PMID- 25756518
TI  - Proteome exploration to provide a resource for the investigation of Ganoderma
      lucidum.
AB  - Ganoderma lucidum is a basidiomycete white rot fungus that has been used for
      medicinal purposes worldwide. Although information concerning its genome and
      transcriptome has recently been reported, relatively little information is
      available for G. lucidum at the proteomic level. In this study, protein fractions
      from G. lucidum at three developmental stages (16-day mycelia, and fruiting
      bodies at 60 and 90 days) were prepared and subjected to LC-MS/MS analysis. A
      search against the G. lucidum genome database identified 803 proteins. Among
      these proteins, 61 lignocellulose degrading proteins were detected, most of which
      (49 proteins) were found in the 90-day fruiting bodies. Fourteen TCA-cycle
      related proteins, 17 peptidases, two argonaute-like proteins, and two
      immunomodulatory proteins were also detected. A majority (470) of the 803
      proteins had GO annotations and were classified into 36 GO terms, with "binding",
      "catalytic activity", and "hydrolase activity" having high percentages.
      Additionally, 357 out of the 803 proteins were assigned to at least one COG
      functional category and grouped into 22 COG classifications. Based on the results
      from the proteomic and sequence alignment analyses, a potentially new
      immunomodulatory protein (GL18769) was expressed and shown to have high
      immunomodulatory activity. In this study, proteomic and biochemical analyses of
      G. lucidum were performed for the first time, revealing that proteins from this
      fungus can play significant bioactive roles and providing a new foundation for
      the further functional investigations that this fungus merits. 

PMID- 25756520
TI  - Automated electrochemical assembly of the protected potential TMG-chitotriomycin
      precursor based on rational optimization of the carbohydrate building block.
AB  - The anomeric arylthio group and the hydroxyl-protecting groups of thioglycosides
      were optimized to construct carbohydrate building blocks for automated
      electrochemical solution-phase synthesis of oligoglucosamines having 1,4-beta
      glycosidic linkages. The optimization study included density functional theory
      calculations, measurements of the oxidation potentials, and the trial synthesis
      of the chitotriose trisaccharide. The automated synthesis of the protected
      potential N,N,N-trimethyl-d-glucosaminylchitotriomycin precursor was accomplished
      by using the optimized building block. 

PMID- 25756521
TI  - Circulating levels of inflammatory cytokines and cytokine receptors in patients
      with ankylosing spondylitis: a cross-sectional comparative study.
AB  - OBJECTIVES: Insight into the most important inflammatory pathways in ankylosing
      spondylitis (AS) could be of importance in risk stratification and the
      development of treatment strategies. Therefore, we aimed to compare circulating
      levels of inflammatory biomarkers between AS patients and controls, and explore
      associations between these biomarkers and clinical measures of disease activity.
      METHOD: In a cross-sectional study, 143 AS patients were compared with 124
      population controls. Blood samples were analysed by immunoassays for interleukin
      (IL)-6, IL-17a, IL-23, soluble tumour necrosis factor receptor 1 (sTNF-R1) and 2
      (sTNF-R2), and osteoprotegerin (OPG). Disease activity was measured by the AS
      Disease Activity Score (ASDAS) and the Bath AS Disease Activity Index (BASDAI).
      RESULTS: Analysis of covariance (ANCOVA) demonstrated elevated plasma levels of
      sTNF-R1 [geometrical mean 0.94 (95% CI 0.88-1.00) vs. 0.83 (95% CI 0.78-0.89)
      ng/mL, p < 0.01] and OPG (2.3, 95% CI 2.1-2.4 vs. 2.0, 95% CI 1.9-2.2 ng/mL, p =
      0.02) and, although not significant, of IL-23 (122, 95% CI 108-139 vs. 106, 95%
      CI 93-120 pg/mL, p = 0.07) in AS patients vs. CONTROLS: More AS patients had a
      high level of sTNF-R2 than controls (22 vs. 1, p < 0.01). No differences between
      the groups were seen for IL-6 and IL-17a. In patients, no significant
      associations were seen between inflammatory markers and disease activity measures
      after adjusting for personal characteristics. CONCLUSION: Significantly higher
      plasma levels of sTNF-R1, sTNF-R2, and OPG and numerically but non-significantly
      higher levels of IL-23 were found in AS patients compared to controls, indicating
      that these cytokines and cytokine receptors are important inflammatory pathways.
      Clinical measures of disease activity were not significantly correlated with
      circulating inflammatory markers.

PMID- 25756522
TI  - Determinants for achieving the LDL-C target of lipid control for secondary
      prevention of cardiovascular events in Taiwan.
AB  - BACKGROUND: Epidemiological and clinical studies have clearly established the
      link between low-density lipoprotein cholesterol (LDL-C) and atherosclerosis
      related cardiovascular consequences. Although it has been a common practice for
      physicians to prescribe lipid-lowering therapy for patients with dyslipidemia,
      the achievement rate is still not satisfied in Taiwan. Therefore, the
      determinants for achieving the LDL-C target needed to be clarified for better
      healthcare of the patients with dyslipidemia. METHOD: This registry-type
      prospective observational study enrolled the patients with cardiovascular
      diseases (coronary artery disease (CAD) and cerebrovascular disease (CVD)) from
      18 medical centers across Taiwan, and clinically followed them for five years. At
      every clinical visit, vital signs, clinical endpoints, adverse events, concurrent
      medications and laboratory specimens were obtained as thoroughly as possible. The
      lipid profile (total cholesterol, high-density lipoprotein cholesterol, LDL-C,
      triglyceride), liver enzymes, and creatinine phosphokinase were evaluated at
      baseline, and every year thereafter. The cross sectional observational data was
      analyzed for this report. RESULT: Among the 3,486 registered patients, 54% had
      their LDL-C < 100 mg/dL. By univariate analysis, the patients achieving the LDL-C
      target were associated with older age, more male sex, taller height, lower blood
      pressure, more under lipid-lowering therapy, more smoking cessation, more history
      of CAD, DM, physical activity, but less history of CVD. The multivariate analysis
      showed statin therapy was the most significant independent determinant for
      achieving the treatment target, followed by age, history of CAD, diabetes, blood
      pressure, and sex. However, most patients were on regimens of very-low to low
      equipotent doses of statins. CONCLUSION: Although the lipid treatment guideline
      adherence is improving in recent years, only 54% of the patients with
      cardiovascular diseases have achieved their LDL-C target in Taiwan, and the most
      significant determinant for this was statin therapy.

PMID- 25756523
TI  - Anticancer activity of sea cucumber triterpene glycosides.
AB  - Triterpene glycosides are characteristic secondary metabolites of sea cucumbers
      (Holothurioidea, Echinodermata). They have hemolytic, cytotoxic, antifungal, and
      other biological activities caused by membranotropic action. These natural
      products suppress the proliferation of various human tumor cell lines in vitro
      and, more importantly, intraperitoneal administration in rodents of solutions of
      some sea cucumber triterpene glycosides significantly reduces both tumor burden
      and metastasis. The anticancer molecular mechanisms include the induction of
      tumor cell apoptosis through the activation of intracellular caspase cell death
      pathways, arrest of the cell cycle at S or G2/M phases, influence on nuclear
      factors, NF-kappaB, and up-down regulation of certain cellular receptors and
      enzymes participating in cancerogenesis, such as EGFR (epidermal growth factor
      receptor), Akt (protein kinase B), ERK (extracellular signal-regulated kinases),
      FAK (focal adhesion kinase), MMP-9 (matrix metalloproteinase-9) and others.
      Administration of some glycosides leads to a reduction of cancer cell adhesion,
      suppression of cell migration and tube formation in those cells, suppression of
      angiogenesis, inhibition of cell proliferation, colony formation and tumor
      invasion. As a result, marked growth inhibition of tumors occurs in vitro and in
      vivo. Some holothurian triterpene glycosides have the potential to be used as P
      gp mediated MDR reversal agents in combined therapy with standard cytostatics. 

PMID- 25756524
TI  - Hydrogen Sulfide Targets the Cys320/Cys529 Motif in Kv4.2 to Inhibit the Ito
      Potassium Channels in Cardiomyocytes and Regularizes Fatal Arrhythmia in
      Myocardial Infarction.
AB  - AIMS: The mechanisms underlying numerous biological roles of hydrogen sulfide
      (H2S) remain largely unknown. We have previously reported an inhibitory role of
      H2S in the L-type calcium channels in cardiomyocytes. This prompts us to examine
      the mechanisms underlying the potential regulation of H2S on the ion channels.
      RESULTS: H2S showed a novel inhibitory effect on Ito potassium channels, and this
      effect was blocked by mutation at the Cys320 and/or Cys529 residues of the Kv4.2
      subunit. H2S broke the disulfide bridge between a pair of oxidized cysteine
      residues; however, it did not modify single cysteine residues. H2S extended
      action potential duration in epicardial myocytes and regularized fatal arrhythmia
      in a rat model of myocardial infarction. H2S treatment significantly increased
      survival by ~1.4-fold in the critical 2-h time window after myocardial infarction
      with a protection against ventricular premature beats and fatal arrhythmia.
      However, H2S did not change the function of other ion channels, including IK1 and
      INa. INNOVATION AND CONCLUSION: H2S targets the Cys320/Cys529 motif in Kv4.2 to
      regulate the Ito potassium channels. H2S also shows a potent regularizing effect
      against fatal arrhythmia in a rat model of myocardial infarction. The study
      provides the first piece of evidence for the role of H2S in regulating Ito
      potassium channels and also the specific motif in an ion channel labile for H2S
      regulation.

PMID- 25756525
TI  - Hypotonic activation of the myo-inositol transporter SLC5A3 in HEK293 cells
      probed by cell volumetry, confocal and super-resolution microscopy.
AB  - Swelling-activated pathways for myo-inositol, one of the most abundant organic
      osmolytes in mammalian cells, have not yet been identified. The present study
      explores the SLC5A3 protein as a possible transporter of myo-inositol in
      hyponically swollen HEK293 cells. To address this issue, we examined the
      relationship between the hypotonicity-induced changes in plasma membrane
      permeability to myo-inositol P ino [m/s] and expression/localization of SLC5A3. P
      ino values were determined by cell volumetry over a wide tonicity range (100-275
      mOsm) in myo-inositol-substituted solutions. While being negligible under mild
      hypotonicity (200-275 mOsm), P ino grew rapidly at osmolalities below 200 mOsm to
      reach a maximum of ~ 3 nm/s at 100-125 mOsm, as indicated by fast cell swelling
      due to myo-inositol influx. The increase in P ino resulted most likely from the
      hypotonicity-mediated incorporation of cytosolic SLC5A3 into the plasma membrane,
      as revealed by confocal fluorescence microscopy of cells expressing EGFP-tagged
      SLC5A3 and super-resolution imaging of immunostained SLC5A3 by direct stochastic
      optical reconstruction microscopy (dSTORM). dSTORM in hypotonic cells revealed a
      surface density of membrane-associated SLC5A3 proteins of 200-2000
      localizations/MUm2. Assuming SLC5A3 to be the major path for myo-inositol, a
      turnover rate of 80-800 myo-inositol molecules per second for a single
      transporter protein was estimated from combined volumetric and dSTORM data.
      Hypotonic stress also caused a significant upregulation of SLC5A3 gene expression
      as detected by semiquantitative RT-PCR and Western blot analysis. In summary, our
      data provide first evidence for swelling-mediated activation of SLC5A3 thus
      suggesting a functional role of this transporter in hypotonic volume regulation
      of mammalian cells.

PMID- 25756527
TI  - The roles of inoculants' carbon source use in the biocontrol of potato scab
      disease.
AB  - Despite the application of multiple strains in the biocontrol of plant diseases,
      multistrain inoculation is still constrained by its inconsistency in the field.
      Nutrients, especially carbons, play an important role in the biocontrol
      processes. However, little work has been done on the systematic estimation of
      inoculants' carbon source use on biocontrol efficacies in vivo. In the present
      study, 7 nonpathogenic Streptomyces strains alone and in different combinations
      were inoculated as biocontrol agents against the potato scab disease, under field
      conditions and greenhouse treatments. The influence of the inoculants' carbon
      source use properties on biocontrol efficacies was investigated. The results
      showed that increasing the number of inoculated strains did not necessarily
      result in greater biocontrol efficacy in vivo. However, single strains with
      higher growth rates or multiple strains with less carbon source competition had
      positive effects on the biocontrol efficacies. These findings may shed light on
      optimizing the consistent biocontrol of plant disease with the consideration of
      inoculants' carbon source use properties. 

PMID- 25756526
TI  - Multivalent nanoparticle networks enable point-of-care detection of human
      phospholipase-A2 in serum.
AB  - A rapid and highly sensitive point-of-care (PoC) lateral flow assay for
      phospholipase A2 (PLA2) is demonstrated in serum through the enzyme-triggered
      release of a new class of biotinylated multiarmed polymers from a liposome
      substrate. Signal from the enzyme activity is generated by the adhesion of
      polystreptavidin-coated gold nanoparticle networks to the lateral flow device,
      which leads to the appearance of a red test line due to the localized surface
      plasmon resonance effect of the gold. The use of a liposome as the enzyme
      substrate and multivalent linkers to link the nanoparticles leads to
      amplification of the signal, as the cleavage of a small amount of lipids is able
      to release a large amount of polymer linker and adhesion of an even larger amount
      of gold nanoparticles. By optimizing the molecular weight and multivalency of
      these biotinylated polymer linkers, the sensitivity of the device can be tuned to
      enable naked-eye detection of 1 nM human PLA2 in serum within 10 min. This high
      sensitivity enabled the correct diagnosis of pancreatitis in diseased clinical
      samples against a set of healthy controls using PLA2 activity in a point-of-care
      device for the first time. 

PMID- 25756528
TI  - Identification of novel QTL governing root architectural traits in an
      interspecific soybean population.
AB  - Cultivated soybean (Glycine max L.) cv. Dunbar (PI 552538) and wild G. soja (PI
      326582A) exhibited significant differences in root architecture and root-related
      traits. In this study, phenotypic variability for root traits among 251 BC2F5
      backcross inbred lines (BILs) developed from the cross Dunbar/PI 326582A were
      identified. The root systems of the parents and BILs were evaluated in controlled
      environmental conditions using a cone system at seedling stage. The G. max parent
      Dunbar contributed phenotypically favorable alleles at a major quantitative trait
      locus on chromosome 8 (Satt315-I locus) that governed root traits (tap root
      length and lateral root number) and shoot length. This QTL accounted for >10% of
      the phenotypic variation of both tap root and shoot length. This QTL region was
      found to control various shoot- and root-related traits across soybean genetic
      backgrounds. Within the confidence interval of this region, eleven transcription
      factors (TFs) were identified. Based on RNA sequencing and Affymetrix expression
      data, key TFs including MYB, AP2-EREBP and bZIP TFs were identified in this QTL
      interval with high expression in roots and nodules. The backcross inbred lines
      with different parental allelic combination showed different expression pattern
      for six transcription factors selected based on their expression pattern in root
      tissues. It appears that the marker interval Satt315-I locus on chromosome 8
      contain an essential QTL contributing to early root and shoot growth in soybean.

PMID- 25756529
TI  - AMP-activated protein kinase: structure, function, and role in pathological
      processes.
AB  - Recently, AMP-activated protein kinase (AMPK) has emerged as a key regulator of
      energy balance at cellular and whole-body levels. Due to the involvement in
      multiple signaling pathways, AMPK efficiently controls ATP-consuming/ATP
      generating processes to maintain energy homeostasis under stress conditions. Loss
      of the kinase activity or attenuation of its expression leads to a variety of
      metabolic disorders and increases cancer risk. In this review, we discuss recent
      findings on the structure of AMPK, its activation mechanisms, as well as the
      consequences of its targets in regulation of metabolism. Particular attention is
      given to low-molecular-weight compounds that activate or inhibit AMPK; the
      perspective of therapeutic use of such modulators in treatment of several common
      diseases is discussed. 

PMID- 25756530
TI  - Methylation of miRNA genes and oncogenesis.
AB  - Interaction between microRNA (miRNA) and messenger RNA of target genes at the
      posttranscriptional level provides fine-tuned dynamic regulation of cell
      signaling pathways. Each miRNA can be involved in regulating hundreds of protein
      coding genes, and, conversely, a number of different miRNAs usually target a
      structural gene. Epigenetic gene inactivation associated with methylation of
      promoter CpG-islands is common to both protein-coding genes and miRNA genes.
      Here, data on functions of miRNAs in development of tumor-cell phenotype are
      reviewed. Genomic organization of promoter CpG-islands of the miRNA genes located
      in inter- and intragenic areas is discussed. The literature and our own results
      on frequency of CpG-island methylation in miRNA genes from tumors are summarized,
      and data regarding a link between such modification and changed activity of miRNA
      genes and, consequently, protein-coding target genes are presented. Moreover, the
      impact of miRNA gene methylation on key oncogenetic processes as well as affected
      signaling pathways is discussed. 

PMID- 25756532
TI  - Effect of chaperonin encoded by gene 146 on thermal aggregation of lytic proteins
      of bacteriophage EL Pseudomonas aeruginosa.
AB  - Investigation of the chaperonin encoded by gene 146 of bacteriophage EL
      Pseudomonas aeruginosa that we characterized earlier has been continued. To
      reveal the mechanism of its functioning, new recombinant substrate proteins,
      fragments of gene product (gp) 183 containing the lysozyme domain were prepared.
      Their interaction with gp146 was studied. The influence of the phage chaperonin
      on the thermal aggregation of one of these gp183 fragments and endolysin (gp188)
      was investigated in both the presence and the absence of ATP by dynamic light
      scattering. In the absence of ATP, the phage chaperonin forms stable complexes
      with substrate proteins, thereby protecting them against thermal aggregation.
      Experimental data obtained for different substrate proteins are analyzed. 

PMID- 25756531
TI  - Possible role of proteases in preconditioning of brain cells to pathological
      conditions.
AB  - Preconditioning (PC) is one of the most effective strategies to reduce the
      severity of cell damage, in particular of nervous tissue cells. Although PC
      mechanisms are studied insufficiently, it is clear that proteases are involved in
      them, but their role has yet been not studied in detail. In this work, some
      mechanisms of a potential recruiting of proteases in PC are considered. Our
      attention is mainly focused on the protease families of caspases and cathepsins
      and on protease receptors. We present evidence that just these proteins are
      involved in the PC of brain cells. A hypothesis is proposed that secreted
      cathepsin B is involved in the realization of PC through activation of PAR2
      receptor. 

PMID- 25756533
TI  - Features of hydrolysis of specific and nonspecific globular proteins and
      oligopeptides by antibodies against viral integrase from blood of HIV-infected
      patients.
AB  - It was shown previously that, as differentiated from canonical proteases, abzymes
      against myelin basic protein (MBP) from blood of patients with multiple sclerosis
      and systemic lupus erythematosus effectively cleaved only MBP, while antibodies
      (ABs) against integrase (IN) from blood of HIV-infected patients specifically
      hydrolyzed only IN. In this work, all sites of effective hydrolysis by anti-IN
      antibodies (IgG and IgM) of 25-mer oligopeptide (OP25) corresponding to MBP were
      identified using reversed-phase and thin-layer chromatographies and MALDI mass
      spectrometry. It was found that amino acid sequences of OP25 and other
      oligopeptides hydrolyzed by anti-MBP abzymes were partially homologous to some
      fragments of the full sequence of IN. Sequences of IN oligopeptides cleavable by
      anti-IN abzymes were homologous to some fragments of MBP, but anti-MBP abzymes
      could not effectively hydrolyze OPs corresponding to IN. The common features of
      the cleavage sites of OP25 and other oligopeptides hydrolyzed by anti-MBP and
      anti-IN abzymes were revealed. The literature data on hydrolysis of specific and
      nonspecific proteins and oligopeptides by abzymes against different protein
      antigens were analyzed. Overall, the literature data suggest that short OPs,
      including OP25, mainly interact with light chains of polyclonal ABs, which had
      lower affinity and specificity to the substrate than intact ABs. However, it
      seems that anti-IN ABs are the only one example of abzymes capable of hydrolyzing
      various oligopeptides with high efficiency (within some hours but not days).
      Possible reasons for the efficient hydrolysis of foreign oligopeptides by anti-IN
      abzymes from HIV-infected patients are discussed. 

PMID- 25756534
TI  - Transcription factor NF-Y inhibits cell growth and decreases SOX2 expression in
      human embryonal carcinoma cell line NT2/D1.
AB  - Transcription factor NF-Y belongs to the embryonic stem cell transcription factor
      circuitry due to its role in the regulation of cell proliferation. We
      investigated the role of NF-Y in pluripotency maintenance using NT2/D1 cells as
      one of the best-characterized human embryonal carcinoma cell line. We
      investigated the efficiency of protein transduction and analyzed the effects of
      forced expression of short isoform of NF-Y A-subunit (NF-YAs) on NT2/D1 cell
      growth and expression of SOX2. We found that protein transduction is an efficient
      method for NF-Y overexpression in NT2/D1 cells. Next, we analyzed the effect of
      NF-YAs overexpression on NT2/D1 cell viability and detected significant reduction
      in cell growth. The negative effect of NF-YAs overexpression on NT2/D1 cell
      pluripotency maintenance was confirmed by the decrease in the level of the
      pluripotency marker SOX2. Finally, we checked the p53 status and determined that
      the NF-Y-induced inhibition of NT2/D1 cell growth is p53-independent. 

PMID- 25756535
TI  - Reorganization of low-molecular-weight fraction of plasma proteins in the annual
      cycle of cyprinidae.
AB  - Reorganization of the low-molecular-weight fraction of cyprinid plasma was
      analyzed using various electrophoretic techniques (disc electrophoresis,
      electrophoresis in polyacrylamide concentration gradient, in polyacrylamide with
      urea, and in SDS-polyacrylamide). The study revealed coordinated changes in the
      low-molecular-weight protein fractions with seasonal dynamics and related
      reproductive rhythms of fishes. We used cultured species of the Cyprinidae family
      with sequenced genomes for the detection of these interrelations in fresh-water
      and anadromous cyprinid species. The common features of organization of fish low
      molecular-weight plasma protein fractions made it possible to make reliable
      identification of their proteins. MALDI mass-spectrometry analysis revealed the
      presence of the same proteins (hemopexin, apolipoproteins, and serpins) in the
      low-molecular-weight plasma fraction in wild species and cultured species with
      sequenced genomes (carp, zebrafish). It is found that the proteins of the first
      two classes are organized as complexes made of protein oligomers. Stoichiometry
      of these complexes changes in concordance with the seasonal and reproductive
      rhythms. 

PMID- 25756536
TI  - Y-box binding protein 1 (YB-1) promotes detection of DNA bulky lesions by XPC
      HR23B factor.
AB  - The nucleotide excision repair system (NER) is one of the main mechanisms
      protecting cellular DNA from lesions caused by such significant environmental
      factors as UV radiation, the influence of polycyclic aromatic hydrocarbons, and
      medical treatment by several antitumor drugs, e.g. cisplatin. One of the major
      NER components is XPC-HR23B, the key factor during the damage recognition step of
      repair. Binding of XPC-HR23B to DNA that contains different bulky lesions
      impairing the structure of DNA is the basis for the wide substrate specificity of
      this DNA repair pathway. The multifunctional protein YB-1 among other protein
      factors has high affinity towards damaged DNA. Involvement of YB-1 in the
      cellular response to genotoxic stress and its ability to interact with damaged
      DNA harboring lesions of various origins pinpoint its putative involvement as a
      modulatory factor in DNA damage recognition and verification steps of NER. In the
      present work, we assayed functional interactions of protein factors XPC-HR23B and
      YB-1 upon binding to DNA structures mimicking damaged DNA containing single bulky
      lesions, as substrates of NER, and bulky lesions combined with abasic sites as an
      example of clustered lesions. The results indicate that YB-1 and XPC-HR23B
      stimulate each other in binding to DNA containing a bulky or clustered lesion,
      which suggests the involvement of YB-1 in the regulation of DNA repair by the NER
      mechanism. 

PMID- 25756537
TI  - Soluble expression and one-step purification of recombinant mouse interferon
      lambda3 in Escherichia coli.
AB  - Interferon (IFN)-lambda3, a member of the type III IFN family, is a pleiotropic
      cytokine that exhibits potent antiproliferative, antiviral, and immunoregulatory
      activities. For further functional study of IFN-lambda3, we developed an
      efficient procedure that includes cloning, expression, and purification to obtain
      relatively large quantity of mouse IFN-lambda3 fusion protein. The mature IFN
      lambda3 protein-coding region was cloned into the prokaryotic expression vector
      pET-44. IFN-lambda3 contains a hexahistidine tag at its C-terminus. We used
      Ni(2+)-nitrilotriacetic acid agarose-affinity chromatography to purify the
      expressed soluble protein. The purified IFN-lambda3 inhibited significantly IL-13
      production in stimulated RAW264.7 macrophages. Our findings show that the
      production of soluble IFN-lambda3 proteins by the pET-44 vector in Escherichia
      coli is a good alternative for the production of native IFN-lambda3 and could be
      useful for the production of other IFN proteins. 

PMID- 25756538
TI  - Enzymatic polymerization of dihydroquercetin using bilirubin oxidase.
AB  - Dihydroquercetin (or taxifolin) is one of the most famous flavonoids and is
      abundant in Siberian larch (Larix sibirica). The oxidative polymerization of
      dihydroquercetin (DHQ) using bilirubin oxidase as a biocatalyst was investigated
      and some physicochemical properties of the products were studied. DHQ oligomers
      (oligoDHQ) with molecular mass of 2800 and polydispersity of 8.6 were obtained by
      enzymatic reaction under optimal conditions. The oligomers appeared to be soluble
      in dimethylsulfoxide, dimethylformamide, and methanol. UV-visible spectra of
      oligoDHQ in dimethylsulfoxide indicated the presence of highly conjugated bonds.
      The synthesized oligoDHQ was also characterized by FTIR and (1)H and (13)C NMR
      spectroscopy. Comparison of NMR spectra of oligoDHQ with DHQ monomer and the
      parent flavonoids revealed irregular structure of a polymer formed via the
      enzymatic oxidation of DHQ followed by nonselective radical polymerization. As
      compared with the monomer, oligoDHQ demonstrated higher thermal stability and
      high antioxidant activity. 

PMID- 25756539
TI  - Cloning and functional expression of a chitinase cDNA from the apple leaf miner
      moth Lithocolletis ringoniella.
AB  - Insect chitinase plays essential roles in chitin catabolism involved in digestion
      and molting during insect development. In the current work, we cloned a chitinase
      cDNA, LrCht5, from the apple leaf miner moth Lithocolletis ringoniella and
      characterized its amino acid sequence and protein properties. The L. ringoniella
      chitinase cDNA was 2136 bp in length with an open reading frame of 1737 bp that
      encodes a polypeptide of 579 amino acid residues with a predicted molecular mass
      of 64.4 kDa and pI of 5.49. The catalytic domain has several phosphorylation and
      glycosylation sites. The recombinant LrCht5 was expressed in Escherichia coli and
      the Spodoptera frugiperda cell line Sf9, and the LrCht5 expressed in insect cells
      exhibited chitinolytic activity. LrCht5 was most stable at pH 6.0 and 45 degrees
      C. This work has potential application in the development of novel and more
      specific synthetic chitinase inhibitors for use as bioinsecticides. 

PMID- 25756540
TI  - Assessing psychosocial functioning following childhood acquired brain injury: The
      Sydney Psychosocial Reintegration Scale for Children.
AB  - OBJECTIVE: The Sydney Psychosocial Reintegration Scale for Children (SPRS-C)
      assesses psychosocial functioning in children with acquired brain injury (ABI).
      This article aims to: (1) describe normative data for the parent-rated SPRS-C
      and, (2) evaluate the discriminant validity of the SPRS-C. METHODS: For Aim 1,
      participants were parents of typically developing children (TDC) aged 5-14 years
      (N = 200). For Aim 2, participants with ABI were aged 5-14 years (n = 26). A
      matched group of TDC was sampled from the larger normative sample to serve as a
      control group (n = 26). RESULTS: For Aim 1, SPRS-C scores across the 10 age-bands
      were in the higher ranges. Correlation coefficients of SPRS-C total score with
      child's age and parent occupational skill level were not statistically
      significant. For Aim 2, SPRS-C scores for the ABI group were significantly lower
      than the control group. CONCLUSIONS: These data provide a guide for clinical
      interpretation of the SPRS-C for measuring psychosocial functioning in children
      with ABI.

PMID- 25756541
TI  - Physiological Performance Determinants of a 22-km Handbiking Time Trial.
AB  - PURPOSE: To investigate physiological performance determinants of the partial
      laps and an overall 22-km handbiking (HB) time trial in athletes with high
      paraplegia. METHODS: Seven male HB athletes with spinal cord injury (lesion
      levels thoracic 2-8) performed a laboratory maximal incremental test under
      cardiorespiratory-mechanical monitoring including respiratory-exchange ratio
      (RER), oxygen uptake (VO2), and mechanical power output (PO). Individual first
      and second ventilatory thresholds (VO 2VT1 and VO 2VT2), VO 2peak, and PO peak
      were posteriorly identified. Athletes also performed a simulated HB time trial
      along a 4-lap bike circuit under cardiorespiratory measurement. Overall metabolic
      cost (C) and %VO 2peak (ratio of VO2 to VO 2peak) were calculated from race data.
      Race performance was defined as mean race velocity (v). RESULTS: athletes
      completed the 22-km HB time trial in 45 +/- 6 min, at 29.9 +/- 3.6 km/h, with %VO
      2peak = 0.86 +/- 0.10 and RER = 1.07 +/- 0.17. VO 2peak (r = .89, P = .01),
      POpeak (r = .85, P = .02), VO 2VT1 (r = .96, P = .001), VO 2VT2 (r = .92, P =
      .003), and C (2nd lap, r = .78; 3rd lap, r = .80; and 4th lap, r = .80) were
      significantly (P < .05) positively correlated with race performance. Within
      subjects correlation coefficient revealed a large and significant (r = .68, P <
      .001) relationship between %VO 2peak and v. CONCLUSIONS: VO 2peak, PO peak,
      ventilatory thresholds, %VO 2peak, and C appeared to be important physiological
      performance determinants of HB time trial.

PMID- 25756542
TI  - Interventions for reducing medication errors in children in hospital.
AB  - BACKGROUND: Many hospitalised patients are affected by medication errors (MEs)
      that may cause discomfort, harm and even death. Children are at especially high
      risk of harm as the result of MEs because such errors are potentially more
      hazardous to them than to adults. Until now, interventions to reduce MEs have led
      to only limited improvements. OBJECTIVES: To determine the effectiveness of
      interventions aimed at reducing MEs and related harm in hospitalised children.
      SEARCH METHODS: The Effective Practice and Organisation of Care Group (EPOC)
      Trials Search Co-ordinator searched the following sources for primary studies:
      The Cochrane Library, including the Cochrane Central Register of Controlled
      Trials (CENTRAL), the Economic Evaluation Database (EED) and the Health
      Technology Assessments (HTA) database; MEDLINE, EMBASE, the Cumulative Index to
      Nursing and Allied Health Literature (CINAHL), PsycINFO, Proquest Dissertations &
      Theses, Web of Science (citation indexes and conference proceedings) and the EPOC
      Register of Studies. Related reviews were identified by searching the Cochrane
      Database of Systematic Reviews and the Database of Abstracts of Reviews of
      Effects (DARE). Review authors searched grey literature sources and trial
      registries. They handsearched selected journals, contacted researchers in the
      field and scanned reference lists of relevant reviews. They conducted searches in
      November 2013 and November 2014. They applied neither language nor date limits.
      SELECTION CRITERIA: Randomised controlled trials, controlled before-after studies
      and interrupted time series investigating interventions to improve medication
      safety in hospitalised children (<= 18 years). Participants were healthcare
      professionals authorised to prescribe, dispense or administer medications.
      Outcome measures included MEs, (potential) patient harm, resource utilisation and
      unintended consequences of the interventions. DATA COLLECTION AND ANALYSIS: Two
      review authors independently selected studies, extracted data and assessed study
      quality using the EPOC data collection checklist. We evaluated the risk of bias
      of included studies and used the GRADE (Grades of Recommendation, Assessment,
      Development and Evaluation) approach to assess the quality of the body of
      evidence. We described results narratively and presented them using GRADE tables.
      MAIN RESULTS: We included seven studies describing five different interventions:
      participation of a clinical pharmacist in a clinical team (n = 2), introduction
      of a computerised physician order entry system (n = 2), implementation of a
      barcode medication administration system (n = 1), use of a structured prescribing
      form (n = 1) and implementation of a check and control checklist in combination
      with feedback (n = 1).Clinical and methodological heterogeneity between studies
      precluded meta-analyses. Although some interventions described in this review
      show a decrease in MEs, the results are not consistent, and none of the studies
      resulted in a significant reduction in patient harm. Based on the GRADE approach,
      the overall quality and strengfh of the evidence are low. AUTHORS' CONCLUSIONS:
      Current evidence on effective interventions to prevent MEs in a paediatric
      population in hospital is limited. Comparative studies with robust study designs
      are needed to investigate interventions including components that focus on
      specific paediatric safety issues.

PMID- 25756543
TI  - Substituent-controlled annuloselectivity and stereoselectivity in the sulfa
      Staudinger cycloadditions.
AB  - In the sulfa-Staudinger cycloadditions of imines and sulfonyl chlorides, the
      annuloselectivity is mainly controlled by the electronic effect of the alpha
      substituents of sulfonyl chlorides and the nucleophilicity of imines. Sulfonyl
      chlorides with weakly electron-donating and withdrawing substituents prefer the
      [2(s)+2(i)] annulation, giving a mixture of cis- and trans-beta-sultams. Sulfonyl
      chlorides bearing strongly electron-withdrawing alpha-substituents show different
      annuloselectivity depending upon the nucleophilicity of imines as following: (1)
      weakly nucleophilic imines with sterically larger substituents than the methyl
      group undergo only [2(s)+2(i)] annulation to produce trans-beta-sultams; (2)
      strongly nucleophilic imines with the N-methyl substituent take place both
      [2(s)+2(i)] and [2(s)+2(i)+2(i)] annulations generally, delivering trans-beta
      sultams and rel(3S,5S,6R)-1,2,4-thiadiazinane 1,1-dioxides composed of one
      molecule of the sulfenes and two molecules of imines; (3) more strongly
      nucleophilic cyclic (Z)-imines give predominately [2(s)+2(i)+2(i)] annulations,
      resulting in a pair of diastereomeric [2(s)+2(i)+2(i)] annuladducts 1,2,4
      thiadiazinane 1,1-dioxides. In the second case, the electronic and steric effects
      of the C-substituents of the N-methyl imines also affect the annuloselectivity.
      The stereochemistry and stereoselectivities of the [2(s)+2(i)] and
      [2(s)+2(i)+2(i)] annuladducts were investigated systematically and
      mechanistically rationalized. 

PMID- 25756545
TI  - Negative evaluations of self and others, and peer victimization as mediators of
      the relationship between childhood adversity and psychotic experiences in
      adolescence: the moderating role of loneliness.
AB  - OBJECTIVE: Previous research has identified an association between traumatic
      experiences and psychotic symptoms. Few studies, however, have explored the
      underlying mechanisms and contingent nature of these associations in an
      integrated model. This study aimed to test a moderated mediation model of
      negative childhood experiences, associated cognitive processes, and psychotic
      experiences within a context of adolescent loneliness. DESIGN: Cross-sectional
      survey. METHODS: A total of 785 Northern Irish secondary school adolescents
      completed the survey. A moderated mediation model was specified and tested.
      RESULTS: Childhood experiences of threat and subordination were directly
      associated with psychotic experiences. Analyses indicated that peer victimization
      was a mediator of this effect and that loneliness moderated this mediated effect.
      CONCLUSION: A new model is proposed to provide an alternative framework for
      assessing the association between trauma and psychotic experience in adolescence
      that recognizes loneliness as a significant contextual moderator that can
      potentially strengthen the trauma-psychosis relationship. PRACTITIONER POINTS:
      Moderated mediation analyses poses an alternative framework to the understanding
      of trauma-psychosis associations Adolescent loneliness is a vulnerability factor
      within this association Data are based on a Northern Irish sample with relatively
      low levels of loneliness Cross-sectional data cannot explore the developmental
      course of these experiences in adolescence.

PMID- 25756547
TI  - Corrigendum: pharmacogenetics: implications for therapy in rheumatic diseases.

PMID- 25756548
TI  - Bone. Targeting epigenetic regulation of osteoclastogenesis to prevent bone loss.

PMID- 25756549
TI  - Successes, challenges and developments in Australian rheumatology.
AB  - Australia is a geographically vast but sparsely populated country with many
      unique factors affecting the practice of rheumatology. With a population
      comprising minority Indigenous peoples, a historically European-origin majority
      population, and recent large-scale migration from Asia, the effect of ethnic
      diversity on the phenotype of rheumatic diseases such as systemic lupus
      erythematosus (SLE) is a constant of Australian rheumatology practice. Australia
      has a strong system of universal healthcare and subsidized access to medications,
      and clinical and research rheumatology are well developed, but inequitable access
      to specialist care in urban and regional centres, and the complex disconnected
      structure of the Australian healthcare system, can hinder the management of
      chronic diseases. 

PMID- 25756550
TI  - Antigen design enhances the immunogenicity of Semliki Forest virus-based
      therapeutic human papillomavirus vaccines.
AB  - Cellular immunity against cancer can be achieved with viral vector- and DNA-based
      immunizations. In preclinical studies, cancer vaccines are very potent, but in
      clinical trials these potencies are not achieved yet. Thus, a rational approach
      to improve cancer vaccines is warranted. We previously demonstrated that the
      relatively low intrinsic immunogenicity of DNA vaccines could be enhanced by
      inclusion of endoplasmic reticulum (ER) targeting and universal helper epitopes
      within the vaccine. We now evaluated whether an optimal antigen format, as
      defined in DNA vaccines, can further enhance the effectiveness of recombinant
      Semliki Forest virus (rSFV) vaccines. To this purpose, we generated,
      characterized and evaluated the efficacy of rSFV replicon particles expressing
      human papillomavirus E6 and/or E7 proteins fused to several helper T-cell
      epitopes and an ER targeting signal. Here, we show that inclusion of a helper
      cassette and an ER targeting signal enhanced protein stability and markedly
      augmented the frequencies of human papillomavirus-specific T cells. Even at an
      immunization dose of as low as 10(5) replicon particles, this novel vaccine
      achieved tumor regression and protection. Thus, even highly effective viral
      vector vaccines can benefit from an improved antigen format, based on the
      inclusion of defined helper epitopes and ER targeting.

PMID- 25756551
TI  - Improvement in verbal memory following SSRI augmentation of antipsychotic
      treatment is associated with changes in the expression of mRNA encoding for the
      GABA-A receptor and BDNF in PMC of schizophrenic patients.
AB  - Verbal memory impairment in schizophrenia is associated with abnormalities in
      gamma-aminobutyric acid (GABA)-ergic and brain-derived neurotrophic factor (BDNF)
      systems. Recent evidence from animal and clinical studies that adding fluvoxamine
      to antipsychotics alters the expression of transcripts encoding for the GABA-A
      receptor and BDNF led us to postulate that fluvoxamine augmentation may improve
      memory in schizophrenia. To test this, we examined the effect of add-on
      fluvoxamine on verbal memory and other cognitive functions and related it to the
      expression of mRNA coding for the GABA-A receptor and BDNF in peripheral
      mononuclear cells (PMC) of schizophrenic patients. Twenty-nine patients completed
      a 6-week study in which fluvoxamine (100 mg/day) was added to ongoing
      antipsychotic treatment. Verbal memory, abstraction working memory, object and
      face recognition, and psychomotor speed and clinical symptoms were assessed at
      baseline and after 3 and 6 weeks of treatment. Blood samples were taken at
      baseline and weeks 1, 3, and 6 and PMC was assayed for the GABA-A beta3 receptor
      and BDNF mRNA by quantitative real-time reverse transcription-PCR. Associative
      and logical verbal memory improved significantly and showed a significant
      correlation with changes in PMC BDNF and GABA-A beta3 receptor mRNA, which
      increased during treatment. Abstraction and object recognition improved, but this
      did not correlate with PMC measures. Negative and positive symptoms improved
      significantly; the latter showed significant correlations with changes in PMC
      measures. Addition of fluvoxamine to antipsychotics improves verbal memory. It is
      postulated that the mechanism involves enhanced GABA-A receptor/BDNF-dependent
      synaptic plasticity in the hippocampus.

PMID- 25756552
TI  - Synthesis, characterization and photocatalytic activity of ZnO nanoparticles
      prepared by biological method.
AB  - Zinc oxide have been produced via a simple green method from zinc nitrate and
      leaf extract aqueous solutions. Prepared ZnO nanoparticles (NPs) were
      investigated by employing through UV-Visible diffuse reflectance spectroscopy (UV
      DRS), photoluminescence (PL) spectroscopy, X-ray diffraction (XRD), Fourier
      transform infrared (FTIR), field emission-scanning electron microscope (FE-SEM),
      and transmission electron microscope (TEM), respectively. The present
      investigation, confirmed the estimated band gap 3.51eV and the PL intensity at
      402nm in visible region are dependent upon the geometrical shape and size of the
      ZnO NPs. The TEM micrograph and XRD pattern confirmed the hexagonal wurtzite
      structure of ZnO NPs. The presence of functional groups and the chemical bonding
      are confirmed by FTIR spectra. EDS shows that the highly pure ZnO nanostructures.
      Moreover, the catalytic activity of synthesized ZnO in the reduction of methylene
      blue was studied by UV-Vis spectroscopy. The effects of process conditions on the
      morphology and size of ZnO have been found from FE-SEM and TEM analyses,
      respectively. 

PMID- 25756553
TI  - Whole-genome copy-number analysis identifies new leads for chromosomal
      aberrations involved in the oncogenesis and metastastic behavior of uveal
      melanomas.
AB  - To further elucidate the genetic underpinnings of uveal melanoma (UM) and
      identify new markers that correlate with disease outcome, archival formalin
      fixed, paraffin-embedded enucleation specimens from 25 patients with UM and a
      mean follow-up of 14 years were analyzed for whole-genome copy-number alterations
      using OncoScan analysis. Copy-number alterations of chromosomes 1, 3, 6, and 8
      were also analyzed in these tumors using multiplex ligation-dependent probe
      amplification, and mutations in GNAQ, GNA11, and BAP1 were searched for by Sanger
      sequencing. Our study confirms the previously reported GNAQ and GNA11 mutation
      frequencies in UMs as well as the presence of monosomy 3 as a factor strongly
      indicating poor prognosis. Two cases with metastatic disease, but without
      monosomy of chromosome 3, showed loss of a small region in the distal part of
      chromosome 2p. Also, UMs leading to metastatic disease had more chromosomal
      aberrations than those without metastases. Three UMs lacking a GNAQ or a GNA11
      mutation showed a gain of chromosome 8q; one of these cases showed extensive
      chromothripsis. Another case (with suspect lung metastasis) showed focal
      chromothripsis. Our whole-genome copy-number analysis shows that focal loss of
      chromosome 2p may be involved in the metastatic spread of UMs without monosomy 3;
      metastatic UMs carry more chromosomal aberrations than those without metastases;
      and chromothripsis may play a role in the oncogenesis of UMs, but does not
      necessarily indicate a poor prognosis. The clinical and particularly diagnostic
      utility of these findings needs to be corroborated in a larger set of patients
      with UM. 

PMID- 25756554
TI  - Effects of electrophotodynamic therapy in vitro on human melanoma cells-
      melanotic (MeWo) and amelanotic (C32).
AB  - Photodynamic therapy has been considered ineffective for melanomas because of the
      competition between the absorbance of melanin from the melanoma and the
      absorbance of photosensitizers at the photosensitizer excitation light
      wavelength. Melanomas show considerable heterogeneity and resistance to
      phototherapy. The effectiveness of photodynamic therapy could be intensified by
      electroporation for enhanced transport of a photosensitizer by transient pores in
      the membrane. In this study, photodynamic therapy combined with electroporation
      was tested in vitro on the human melanoma cell lines melanotic melanoma (MeWo)
      and amelanotic melanoma (C32). Control experiments were conducted on human
      keratinocytes (HaCaT). Photofrin was used as a photosensitizer. Photosensitizer
      distribution, cloning efficacy test, comet assay, and assessment of apoptotic
      proteins were performed. Melanin levels were determined before and after
      photodynamic therapy. The experiments indicated that electroporation effectively
      supports the photodynamic method. It was found that photodynamic therapy with
      electroporation efficiently induces apoptosis in melanotic and amelanotic
      melanoma cells. 

PMID- 25756556
TI  - The Validity and Clinical Utility of the COVERS Scale and Pain Assessment Tool
      for Assessing Pain in Neonates Admitted to an Intensive Care Unit.
AB  - OBJECTIVES: Infants admitted to a neonatal intensive care unit (NICU) are
      routinely subject to a range of painful procedures. However, pain assessments in
      NICUs are under-utilized due to a lack of a gold standard pain measure. In this
      study we assessed the psychometric properties and clinical utility of the COVERS
      and Pain Assessment Tool (PAT), in a neonatal unit. METHODS: We had 72 nurses use
      the scales to assess pain at baseline and during a heel-lance procedure in 80
      NICU infants. An independent research observer and the infant's mother also
      completed pain ratings. After the study, we assessed nurse preference and
      clinical utility ratings for both scales. RESULTS: The COVERS had satisfactory
      internal consistency at baseline (Cronbach alpha=0.74) and heel lance
      (alpha=0.78), as did the PAT (baseline alpha=0.79, heel lance alpha=0.85).
      Intraclass correlation coefficients demonstrated good inter-rater reliability at
      baseline and heel lance, respectively, for both the COVERS (0.82 and 0.80) and
      the PAT (0.83 and 0.86). There were strong associations between total scores on
      the 2 scales at baseline (r=0.81, P<0.001) and heel lance (r=0.91, P<0.001),
      between researcher's ratings and total COVERS (rho=0.75, P<0.001) and PAT scores
      (rho=0.69, P<0.001), and between maternal ratings and total COVERS (r=0.74,
      P<0.05) and PAT scores (r=0.65, P<0.05). Both scales were sensitive to pain and
      nonpain events. Reliability and validity was mostly upheld across gestational
      age. Most nurses preferred the COVERS (52%) to the PAT (16%), and 32% had no
      preference. DISCUSSION: This study builds on evidence for the COVERS scale and
      the PAT; both scales were reliable and valid measures of acute pain in neonates
      as premature as 24-week gestational age.

PMID- 25756557
TI  - TNF Block Gene Variants Associate With Pain Intensity in Black Southern Africans
      With HIV-associated Sensory Neuropathy.
AB  - OBJECTIVES: HIV-associated sensory neuropathy (HIV-SN) is a common neurological
      complication of HIV infection, and it is often painful. Tumor necrosis factor
      (TNF)-alpha is implicated in neuropathic pain, but associations between
      neuropathic pain and polymorphisms in the TNFA gene have not been identified. The
      "TNF block" is a region of high linkage disequilibrium within the central major
      histocompatability complex that contains several genes involved in the regulation
      of inflammation, including TNFA. Polymorphisms in the block have been associated
      with an altered risk of HIV-SN, but no investigations into whether this region is
      associated with the painful symptoms of neuropathy have been undertaken.
      Therefore, we investigated whether polymorphisms in the TNF block are associated
      with pain intensity in black Southern Africans with HIV-SN. METHODS: Single
      nucleotide polymorphisms (SNPs) defining TNF block haplotypes and African
      specific tagSNPs were genotyped in samples from 150 black Southern Africans with
      HIV-SN. RESULTS: One SNP allele, rs28445017*A, was significantly associated with
      an increased pain intensity after correction for age, sex, and the CD4 T-cell
      count. A common 3-SNP haplotype containing rs28445017*G remained associated with
      a reduced pain intensity after correction for covariates and multiple
      comparisons. DISCUSSION: We identified a novel genetic association between
      polymorphisms in the TNF block and the pain intensity in black Southern Africans
      with HIV-SN. Our study implicates rs28445017 in painful HIV-SN, although its
      precise role and whether it may be causative is unclear. rs28445017 was not
      associated with the risk for HIV-SN as such, highlighting potential differences
      between the pathophysiology of the neuropathy and the painful features of the
      neuropathy.

PMID- 25756558
TI  - Digital Pain Drawings: Assessing Touch-Screen Technology and 3D Body Schemas.
AB  - OBJECTIVES: To assess the consistency and level of agreement between pain
      drawings collected on (1) paper and a personal computer tablet; and (2) between a
      2-dimensional (2D) line drawing and 3-dimensional (3D) body schema. MATERIALS AND
      METHODS: Pain-free participants (N=24) recreated a premarked "pain" area from a
      2D line drawing displayed on paper onto paper or tablet, and individuals with
      chronic neck pain (N=29) expressed their current pain on paper and tablet. A
      heterogeneous group (N=26) was recruited from cross-disciplinary pain clinic and
      expressed their pain on a 2D line drawing and a 3D body schema, as displayed on a
      tablet, and then completed an user-experience questionnaire. RESULTS: Pain
      drawings showed moderate to high level of consistency and a high level of
      agreement for paper and tablet and between 2D line drawing and 3D body schema. A
      fixed bias (-1.0042, P<0.001) revealed that pain areas were drawn slightly
      smaller on paper than on tablet, and larger on the 2D than the 3D body schema (
      0.6371, P=0.003), as recorded on a tablet. Over one-third of individuals with
      chronic pain preferred and/or believed that the 3D body schema enabled a more
      accurate record; 12 believed they were equal, and 3 preferred the 2D line
      drawing. DISCUSSION: Pain drawings recorded with touch-screen technology provide
      equal reliability to paper but the size of the drawing slightly differs between
      the platforms. Although, 2D line drawings and 3D body schemas were similar in
      terms of consistency and reliability, it remains to be confirmed whether 3D body
      schemas increase the accuracy and precision of pain drawings.

PMID- 25756559
TI  - Interviewing and Urine Drug Toxicology Screening in a Pediatric Pain Management
      Center: An Analysis of Analgesic Nonadherence and Aberrant Behaviors in
      Adolescents and Young Adults.
AB  - OBJECTIVES: Many adolescents and young adults report having chronic pain. Urine
      drug toxicology (UDT) is not routinely used in the pediatric pain management
      population, despite more routine use in adults with pain, particularly those
      prescribed opioids. As a first step toward establishing monitoring practices in
      pediatric and adolescent pain management, the present study evaluated the role of
      UDT in conjunction with a standard clinical interview in identifying the rate of
      adherence to an established analgesic regimen. The study also aimed to assess the
      use of UDT in identifying possible aberrant behaviors in this population.
      METHODS: Data were acquired from a convenience sample of 50 pediatric and
      adolescent pain management initial consultations, during which a clinical
      interview and UDT were conducted. Data were analyzed to determine adherence to an
      established analgesic prescription regimen, and for identification of aberrant
      behaviors including concurrent use of illicit substances and prescription
      medication misuse. Other pertinent demographic and clinical factors were examined
      as factors in adherence. RESULTS: Opioid medications were prescribed for 42% of
      the sample receiving pain medications, and 22% of the sample was nonadherent to
      their prescription analgesic regimen. Factors associated with a higher likelihood
      of nonadherence were an older age and having an opioid prescription. The majority
      (90%) of those nonadherent to their analgesic regimen displayed some form of
      aberrant behavior. Among the nonadherent patients, 50% were identified by UDT
      alone, and 50% were identified by self-report during the clinical encounter.
      CONCLUSIONS: These results highlight the challenges of identifying nonadherence
      to a prescription regimen among adolescents with chronic pain. In addition, this
      preliminary work suggests that UDT could be used in conjunction with careful
      clinical interviewing to substantiate patient report and increase the likelihood
      of detecting analgesic nonadherence and aberrant behaviors.

PMID- 25756560
TI  - Prior Opioid Use Does Not Impact the Response to Pregabalin in Patients With
      Fibromyalgia.
AB  - OBJECTIVE: Fibromyalgia (FM) is a chronic pain disorder for which pregabalin is
      an approved treatment in the United States. Although opioids are not a
      recommended treatment option, they continue to be used by many FM patients. The
      impact of patients' prior opioid use on their subsequent response to pregabalin
      has not been assessed. METHODS: This was a pooled analysis of 4 clinical trials
      to assess the efficacy of pregabalin in FM patients both with and without prior
      opioid use. Patients were divided into those using opioids prior to the trial and
      those who were not. The change in least squares mean pain score (assessed by 0 to
      10 numeric rating scale) with pregabalin compared with placebo was assessed
      together with FM symptoms, anxiety, and depression. RESULTS: There were 2062
      patients in the analysis set, including 371 patients with prior opioid use. Equal
      numbers of patients were treated with placebo, pregabalin 300 mg/d, and
      pregabalin 450 mg/d. Pregabalin significantly improved the least squares mean
      (95% confidence interval) difference in pain score compared with placebo in
      patients both with and without prior opioid use 0.87 (0.34-1.41) and 0.41 (0.17
      0.65), respectively, at 300 mg/d and 0.91 (0.39-1.44) and 0.72 (0.48-0.96) at 450
      mg/d (P<=0.001 for all). FM symptoms, anxiety, and depression were also improved
      with pregabalin compared with placebo, regardless of prior opioid use.
      DISCUSSION: FM patients respond to treatment with pregabalin with significant
      improvements in pain scores irrespective of prior opioid use. These data could
      inform treatment decisions for FM patients with prior use of opioids.

PMID- 25756561
TI  - VT or not VT: That is the question.

PMID- 25756562
TI  - Cardiac denervation in Takotsubo syndrome.

PMID- 25756563
TI  - Recurrent coronary vasospasm-induced acute coronary syndrome complicated by
      cardiac arrest.

PMID- 25756564
TI  - A difficult but successful cross-over using a Snare catheter to secure the 18F
      arterial puncture. Implications for the TAVI daily practice.

PMID- 25756565
TI  - Cardiovascular risk factors and disease in patients with hypothalamic-pituitary
      disorders.

PMID- 25756567
TI  - A quick bailout ongoing of cardiogenic shock and iatrogenic dissection of the
      left main coronary artery.

PMID- 25756566
TI  - Worsening diastolic function is associated with elevated fasting plasma glucose
      and increased left ventricular mass in a supra-additive fashion in an elderly,
      healthy, Swedish population.
AB  - AIMS: To examine whether increasing fasting plasma glucose (FPG) levels were
      associated with worsening left ventricular (LV) diastolic function, independently
      of LV mass index (LVMI) in elderly, otherwise healthy subjects. METHODS AND
      RESULTS: We tested cross-sectional associations between echocardiographically
      determined averaged E/e ratio/diastolic function, LVMI, cardiovascular risk
      factors, and FPG categorized as normal (NFG), impaired (IFG), and new-onset
      diabetes mellitus (DM), in 483 men and 208 women aged 56-79 years without overt
      cardiovascular disease, who received no cardiovascular, anti-diabetic, or lipid
      lowering drugs and had a preserved LV ejection fraction >50%. Median E/e was
      significantly higher among subjects with diabetes than those without (8 vs. 7; p
      = 0.03), as was the prevalence of grade 2 or 3 diastolic dysfunction (25% vs.
      16%; p = 0.02). E/e and diastolic function were significantly associated with
      LVMI (p <= 0.002), but not FPG category, on multivariable analysis. However,
      interaction analyses revealed that increasing LVMI was primarily associated with
      worsening diastolic function (higher E/e) in subjects with FPG > 6 mmol/L
      (beta=0.005 for IFG and DM vs. 0.001 for NFG; p = 0.02), whereas increasing
      systolic blood pressure was primarily associated with worsening diastolic
      function (higher E/e) in subjects with FPG <= 6.9 mmol/L (beta = 0.005 for NFG
      and 0.003 for IFG vs. -0.001 for DM; p=0.001). CONCLUSION: Diastolic dysfunction
      was significantly more prevalent among patients with DM than those without. The
      importance of LVMI increased, but the importance of systolic blood pressure
      decreased with higher FPG category.

PMID- 25756568
TI  - Increased circulating malondialdehyde-modified low-density lipoprotein levels in
      patients with ergonovine-induced coronary artery spasm.
AB  - OBJECTIVE: Coronary endothelial dysfunction is thought to underlie the
      development of coronary artery spasms. Malondialdehyde-modified low-density
      lipoprotein (MDA-LDL) was suggested as a marker of endothelial damage. This study
      investigated the diagnostic impact of MDA-LDL on ergonovine-induced coronary
      spasms. METHODS: We included 152 patients with suspected coronary spastic angina.
      MDA-LDL levels were measured before an ergonovine provocation test. Coronary
      spasm was defined as total or subtotal occlusion, compared to the relaxed state
      after nitroglycerin, associated with ischemic ECG changes and concurrent chest
      pain. Changes in vessel diameter in response to ergonovine were evaluated with
      quantitative coronary angiography. RESULTS: Coronary spasms were observed in 41
      patients (27%). MDA-LDL levels were significantly higher in patients with spasms
      compared to those without spasms (139.9 +/- 45.9 U/L vs. 109.6 +/- 36.6 U/L,
      p<0.01). Univariate logistic regression analyses indicated significant
      relationships between coronary spasms and MDA-LDL (per 10 U/L, odds ratio (OR):
      1.20; p<0.01), high-density lipoprotein (per 10 mg/dL, OR: 0.76; p=0.03), smoking
      (OR: 3.04; p<0.01), and male gender (OR: 3.51; p<0.01). In the multivariate
      model, MDA-LDL (per 10 U/L, OR: 1.17; p<0.01) remained a significant predictor of
      coronary spasm. Regression analysis showed a positive correlation between MDA-LDL
      levels and coronary luminal diameter changes induced by ergonovine (r=0.57,
      p<0.01). The optimal MDA-LDL threshold for predicting coronary spasm was 121.3
      U/L, identified with a receiver operating characteristic curve. CONCLUSIONS:
      Increased circulating MDA-LDL levels were associated with ergonovine-induced
      coronary artery spasm.

PMID- 25756569
TI  - Is obstructive sleep apnea associated with the risk of ischemic stroke in
      patients with atrial fibrillation?

PMID- 25756570
TI  - Percutaneous treatment of aortic coarctation with new generation self expandable
      stent system and the images of 320-slice tomographic angiography.

PMID- 25756571
TI  - Does professional athlete training cause acquired left ventricular
      hypertrabeculation/noncompaction?

PMID- 25756572
TI  - Response to letter by Hendrik Bonnemeier: Is it coronary kinking or vasospasm
      induced myocardial ischemia?

PMID- 25756573
TI  - Early development of coronary artery aneurysms after implantation of biolimus
      eluting stent with biodegradable polymer.

PMID- 25756574
TI  - Ankle brachial index teaching: A call for an international action.

PMID- 25756575
TI  - Takotsubo cardiomyopathy: Utility of cardiac magnetic resonance to stratify risk
      for sudden cardiac death.

PMID- 25756576
TI  - A multidisciplinary approach in early stent thrombosis: Insights from optical
      coherence tomography and platelet reactivity testing.

PMID- 25756577
TI  - Necessity of magnetic resonance imaging examinations after permanent pacemaker
      implantation.

PMID- 25756578
TI  - Left main coronary artery and ostial left anterior descending coronary artery
      stenting in a single coronary artery during NSTEMI. The OCT response.

PMID- 25756579
TI  - Impact of low dose atorvastatin on development of new-onset diabetes mellitus in
      Asian population: Three-year clinical outcomes.
AB  - BACKGROUND: High dose atorvastatin is known to be associated with new onset
      diabetes mellitus (NODM) in patients with high risk for developing diabetes
      mellitus (DM). However, low dose atorvastatin is more commonly used as compared
      with high dose atorvastatin. The aim of this study is to investigate the impact
      of low dose atorvastatin (LDA, 10mg or 20mg) on the development of NODM up to
      three years in Asian patients. METHODS: From January 2004 to September 2009, we
      investigated a total of 3566 patients who did not have DM. To adjust for
      potential confounders, a propensity score matching (PSM) analysis was performed
      using the logistic regression model. After PSM (C-statistics: 0.851), a total of
      818 patients (LDA group, n=409 patients and control group, n=409 patients) were
      enrolled for analysis. RESULTS: Before PSM, the cumulative incidence of NODM
      (5.8% vs. 2.1%, p<0.001), myocardial infarction (0.5% vs. 0.1%, p-value=0.007),
      and major adverse cardio-cerebral event (MACCE, 1.8% vs. 0.7%, p-value=0.012) at
      three-years were higher in the LAD group. However, after PSM, there was a trend
      toward higher incidence of NODM (5.9% vs. 3.2%, p=0.064) in the LDA group, but
      the incidence of MACCE (1.2% vs. 1.5%, p-value=1.000) was similar between the two
      groups. In multivariable analysis, the LDA administration was tended to be an
      independent predictor of NODM (OR: 1.99, 95% CI: 1.00-3.98, p-value 0.050).
      CONCLUSIONS: In this study, the use of LDA tended to be a risk factor for NODM in
      Asian patients and reduced clinical events similar to the control group. However,
      large-scale randomized controlled trials will be needed to get the final
      conclusion.

PMID- 25756580
TI  - Iatrogenic constrictive remodeling of left main stem after left coronary cusp
      atrial tachycardia ablation.

PMID- 25756581
TI  - Promotion of "Low T" and citation bias in testosterone studies.

PMID- 25756582
TI  - Digoxin or digoxin prescribed patient? Randomized trials are essential to
      discriminate the principal risk factor for the association of digoxin and
      increased mortality.

PMID- 25756583
TI  - Evaluation of apoptotic pathway in oral mucosa by smoking in a Brazilian
      Outpatient Smoking Cessation Program.

PMID- 25756584
TI  - Baroreceptor dysfunction, diabetes mellitus, and takotsubo syndrome: An intricate
      triangle needing exploration.

PMID- 25756585
TI  - Malignant peripheral nerve sheath tumor in cowden syndrome: a first report.
AB  - Malignant peripheral nerve sheath tumor is a rare malignancy, accounting for 3%
      to 10% of all soft-tissue sarcomas. We describe a previously healthy 48-year-old
      man who was diagnosed as having a high-grade malignant neoplasm involving the
      facial nerve in the right petrous canal after a 4-year history of deafness. The
      tumor was resected; histologic appearance and immunophenotype, including patchy
      but strong positivity for S100 protein, indicated a diagnosis of malignant
      peripheral nerve sheath tumor. A PTEN mutation, c.1003C>T p.(Arg335Ter), was
      subsequently identified as the cause of Cowden syndrome in another family member
      (a nephew) with dysplastic gangliocytoma of the cerebellum (Lhermitte-Duclos
      disease), and genetic testing in the proband's daughter indicated that he was an
      obligate carrier of the mutation. Sequencing of the tumor showed homozygosity for
      c.1003C>T, confirming the presence of a germline mutation and implying loss of
      the second allele. With the exception of Lhermitte-Duclos disease, tumors of the
      nervous system are not a prominent feature of Cowden syndrome, and this is the
      first report of malignant peripheral nerve sheath tumor in Cowden syndrome.
      Sequencing results in the tumor lend evidence to PTEN gene inactivation being
      implicated in tumorigenesis in this case, suggesting causality rather than chance
      association.

PMID- 25756586
TI  - Drosha inclusions are new components of dipeptide-repeat protein aggregates in
      FTLD-TDP and ALS C9orf72 expansion cases.
AB  - Frontotemporal lobar degeneration (FTLD) and amyotrophic lateral sclerosis (ALS)
      are 2 neurodegenerative disorders that share clinical, genetic, and
      neuropathologic features. The presence of abnormal expansions of GGGGCC repeats
      (G4C2 repeats) in a noncoding region of the Chromosome 9 open reading frame 72
      (C9orf72) gene is the major genetic cause of both FTLD and ALS. Transcribed G4C2
      repeats can form nuclear RNA foci and recruit RNA-binding proteins, thereby
      inhibiting their normal function. Moreover, through a repeat-associated non-ATG
      translation mechanism, G4C2 repeats translation leads to dipeptide-repeat protein
      aggregation in the cytoplasm of neurons. Here, we identify Drosha protein as a
      new component of these dipeptide-repeat aggregates. In C9orf72 mutation cases of
      FTLD-TDP (c9FTLD-TDP) and ALS (c9ALS), but not in FTLD or ALS cases without
      C9orf72 mutation, Drosha is mislocalized to form neuronal cytoplasmic inclusions
      in the hippocampus, frontal cortex, and cerebellum. Further characterization of
      Drosha-positive neuronal cytoplasmic inclusions in the hippocampus, frontal
      cortex, and cerebellum revealed colocalization with p62 and ubiquilin-2, 2
      pathognomonic signatures of c9FTLD-TDP and c9ALS cases; however, Drosha
      inclusions rarely colocalized with TDP-43 pathology. We conclude that Drosha may
      play a unique pathogenic role in the onset or progression of FTLD-TDP/ALS in
      patients with the C9orf72 mutation.

PMID- 25756587
TI  - Familial behavioral variant frontotemporal dementia associated with astrocyte
      predominant tauopathy.
AB  - A familial behavioral variant frontotemporal dementia associated with astrocyte
      predominant tauopathy is described in 2 sisters born from consanguineous parents.
      The neuropathologic examination revealed massive accumulation of abnormally
      hyperphosphorylated, conformational, truncated tau at aspartic acid 421,
      ubiquitinated and nitrated tau at Tyr29 in cortical astrocyte (including their
      perivascular foot processes), and Bergmann glia. Smaller amounts of abnormal tau
      were observed in neurons and rarely in oligodendrocytes. There was decreased
      expression of glial glutamate transporter in the majority of tau-positive
      astrocytes. Gel electrophoresis of sarkosyl-insoluble fractions showed 2 bands of
      64 and 60 kDa and a doublet of 67 to 70 kDa (which are different from those seen
      in Alzheimer disease and in typical 4R and 3R tauopathies) together with several
      bands of lower molecular weight indicative of truncated tau. Analysis of the
      expression of MAPT isoforms further revealed altered splicing and representation
      of tau isoforms involving exons 2, 3, and 10. Genetic testing revealed no known
      mutations in PSEN1, PSEN2, APP, MAPT, GRN, FUS, and TARDBP and no pathologic
      expansion in C9ORF72. However, a novel rare heterozygous sequence
      variant(p.Q140H) of uncertain significance was identified in FUS in both
      siblings.

PMID- 25756589
TI  - Expression of regulatory proteins in choroid plexus changes in early stages of
      Alzheimer disease.
AB  - Recent studies indicate that the choroid plexus has important physiologic and
      pathologic roles in Alzheimer disease (AD). To obtain additional insight on
      choroid plexus function, we performed a proteomic analysis of choroid plexus
      samples from patients with AD stages I to II (n = 16), III to IV (n = 16), and V
      to VI (n = 11) and 7 age-matched control subjects. We used 2-dimensional
      differential gel electrophoresis coupled with mass spectrometry to generate a
      complete picture of changes in choroid plexus protein expression occurring in AD
      patients. We identified 6 proteins: 14-3-3 beta/alpha, 14-3-3 epsilon, moesin,
      proteasome activator complex subunit 1, annexin V, and aldehyde dehydrogenase,
      which were significantly regulated in AD patient samples (p < 0.05, >1.5-fold
      variation in expression vs control samples). These proteins are implicated in
      major physiologic functions including mitochondrial dysfunction and apoptosis
      regulation. These findings contribute additional significance to the emerging
      importance of molecular and functional changes of choroid plexus function in the
      pathophysiology of AD.

PMID- 25756590
TI  - Neuroinflammatory signals in Alzheimer disease and APP/PS1 transgenic mice:
      correlations with plaques, tangles, and oligomeric species.
AB  - To understand neuroinflammation-related gene regulation during normal aging and
      in sporadic Alzheimer disease (sAD), we performed functional genomics analysis
      and analyzed messenger RNA (mRNA) expression by quantitative reverse
      transcription-polymerase chain reaction of 22 genes involved in neuroinflammation
      like responses in the cerebral cortex of wild-type and APP/PS1 transgenic mice.
      For direct comparisons, mRNA expression of 18 of the same genes was then analyzed
      in the entorhinal cortex, orbitofrontal cortex, and frontal cortex area 8 of
      middle-aged human subjects lacking Alzheimer disease-related pathology and in
      older subjects with sAD pathology covering Stages I-II/0(A), III-IV/A-B, and V
      VI/C of Braak and Braak classification. Modifications of cytokine and immune
      mediator mRNA expression were found with normal aging in wild-type mice and in
      middle-aged individuals and patients with early stages of sAD-related pathology;
      these were accompanied by increased protein expression of certain mediators in
      ramified microglia. In APP/PS1 mice, inflammatory changes coincided with beta
      amyloid (Abeta) deposition; increased levels of soluble oligomers paralleled the
      modified mRNA expression of cytokines and mediators in wild-type mice. In
      patients with sAD, regulation was stage- and region-dependent and not merely
      acceleration and exacerbation of mRNA regulation with aging. Gene regulation at
      first stages of AD was not related to hyperphosphorylated tau deposition in
      neurofibrillary tangles, Abeta plaque burden, concentration of Abeta1-40
      (Abeta40) and Abeta1-42 (Abeta42), or fibrillar Abeta linked to membranes but
      rather to increased levels of soluble oligomers. Thus, species differences and
      region- and stage-dependent inflammatory responses in sAD, particularly at the
      initial stages, indicate the need to identify new anti-inflammatory compounds
      with specific molecular therapeutic targets. 

PMID- 25756588
TI  - Hippocampal endosomal, lysosomal, and autophagic dysregulation in mild cognitive
      impairment: correlation with abeta and tau pathology.
AB  - Endosomal-lysosomal and autophagic dysregulation occurs in the hippocampus in
      prodromal Alzheimer disease (AD), but its relationship with beta-amyloid (Abeta)
      and tau pathology remains unclear. To investigate this issue, we performed
      immunoblot analysis of hippocampal homogenates from cases with an antemortem
      clinical diagnosis of no cognitive impairment, mild cognitive impairment (MCI),
      and AD. Western blot analysis revealed significant increases in the acid
      hydrolase cathepsin D and early endosome marker rabaptin5 in the MCI group
      compared with AD, whereas levels of phosphorylated mammalian target of rapamycin
      proteins (pmTOR), total mammalian target of rapamycin (mTOR), p62, traf6, and
      LilrB2 were comparable across clinical groups. Hippocampal Abeta1-40 and Abeta1
      42 concentrations and AT8-immunopositive neurofibrillary tangle density were not
      significantly different across the clinical groups. Greater cathepsin D
      expression was associated with global cognitive score and episodic memory score
      but not with mini mental state examination or advanced neuropathology criteria.
      These results indicate that alterations in hippocampal endosomal-lysosomal
      proteins in MCI are independent of tau or Abeta pathology. 

PMID- 25756591
TI  - TIMP-1 overexpression in lung carcinoma enhances tumor kinetics and angiogenesis
      in brain metastasis.
AB  - Tissue inhibitors of matrix metalloproteinase (TIMP) orchestrate many biologic
      activities, including inhibition of matrix metalloproteinase activity, activation
      of pro-matrix metalloproteinases, and regulation of cell proliferation,
      angiogenesis, and apoptosis induction. Tissue inhibitors of matrix
      metalloproteinase can play a protective role during tumor invasion and
      metastasis, but elevated TIMP messenger RNA levels have also been associated with
      aggressive cancers and poor clinical outcome. We examined the potential roles of
      TIMP-1 in H2009 lung adenocarcinoma cells and in cells transfected with a human
      TIMP-1-overexpressing vector (HB-6 and HB-1). Tumors resulting from the
      implantation of parental cell lines and transfected HB-1 cells into the brains of
      nude mice had a typical carcinoma profile, but human TIMP-1-overexpressing tumors
      showed enhanced tumor kinetics and focally more infiltrative features; vessel
      density assessed with anti-CD31 immunohistochemistry was also greater within HB-1
      tumor implants. Similar effects on HB-6 and HB-1 cells versus parental cell lines
      and empty vector clones were observed in endothelial cell assays. Anchorage
      independent growth and invasion through Matrigel were also increased in TIMP-1
      overexpressing cells. Together, these results indicate tumor-promoting functions
      of TIMP-1 through alterations in angiogenesis, increased tumorigenicity, and
      invasive behavior. Although matrix metalloproteinase inhibition has been the
      traditionally identified function of TIMP-1, matrix metalloproteinase-independent
      interactions may contribute to the growth of metastatic carcinomas in the brain. 

PMID- 25756592
TI  - Critical contribution of adenosine A2A receptors in bone marrow-derived cells to
      white matter lesions induced by chronic cerebral hypoperfusion.
AB  - Adenosine A2A receptors (A2ARs) in distinct cellular types may exert different
      and even opposite effects on many neurologic disorders; A2ARs in bone marrow
      derived cells (BMDCs) have been shown to play important roles in various brain
      injuries. We previously showed that global A2AR inactivation aggravates chronic
      cerebral hypoperfusion-induced white matter lesions (WMLs); however, the specific
      cell populations responsible for A2AR-mediated signaling remain unknown. In the
      present study, we developed chimeric mice in which A2ARs were either selectively
      inactivated or reconstituted in BMDCs by transplanting bone marrow from global
      A2AR gene knockout or wild-type mice into wild-type or gene knockout mice,
      respectively. Chimeric mice were subsequently subjected to chronic cerebral
      hypoperfusion by bilateral common carotid artery stenosis, and the effects of
      BMDC A2ARs on WMLs were evaluated. The selective inactivation of A2AR in BMDCs
      aggravated chronic cerebral hypoperfusion-induced WMLs, promoted microglial
      activation, and increased proinflammatory cytokine expression, whereas the
      selective reconstitution or activation of A2AR in BMDCs using the agonist
      CGS21680 produced the opposite effects. These results demonstrate that A2ARs in
      BMDCs are important modulators of WMLs induced by chronic cerebral hypoperfusion;
      this modulation might be associated with the regulation of inflammatory cytokine
      production.

PMID- 25756593
TI  - Bile acid binding capacity of fish protein hydrolysates from discard species of
      the West Mediterranean Sea.
AB  - Fish protein hydrolysates (FPH), produced from the six main discard species from
      the West Mediterranean Sea (sardine, horse mackerel, axillary seabream, bogue,
      small-spotted catshark and blue whiting) were tested for their bile acid binding
      capacity. This capacity is directly linked to the ability to inhibit bile
      reabsorption in the ileum and therefore to lower cholesterol levels in the
      bloodstream. From each species, FPH were obtained by three different enzymatic
      treatments employing two serine endoproteases (subtilisin and trypsin)
      sequentially or in combination. The results show statistically significant
      differences among the fish species, attaining interesting average values of bile
      acid binding capacity for blue whiting (27.32% relative to cholestyramine on an
      equal protein basis) and horse mackerel (27.42% relative to cholestyramine on an
      equal protein basis). The enzymatic treatments did not significantly affect the
      ability of a given species to bind bile acids. These results are similar to other
      protein sources, such as soy protein or casein, of proven hypocholesterolemic
      effect. It can be concluded that fish protein hydrolysates from these discard
      species are suitable as ingredients in the formulation of cholesterol-lowering
      supplements. 

PMID- 25756594
TI  - The risk and severity of developing symptomatic palpitations when prescribed
      mirabegron for overactive bladder.
AB  - OBJECTIVES: Mirabegron is a new selective beta3-adrenoreceptor agonist licensed
      for the treatment of overactive bladder (OAB). In clinical trials, mirabegron is
      well-tolerated with a low side-effect profile. There is little data available on
      the risks in a non-selected population. The presence of beta-adrenoreceptors in
      cardiac and vascular tissue leads to the possibility of the development of
      adverse cardiovascular events. We conducted a consecutive cohort study to assess
      the risk of developing palpitations, the severity of the condition and to
      investigate any underlying risk factors that predispose patients with OAB to
      develop palpitations whilst taking mirabegron. STUDY DESIGN: A consecutive cohort
      of patients with OAB was studied between February 2013 and June 2014. Patients
      were prescribed mirabegron 50mg daily and outcomes assessed at 6 weeks. Patients
      with known cardiac arrhythmias were excluded. In patients who developed
      palpitations, a detailed account of their symptoms and medical history were
      documented and a 12-lead electrocardiogram (ECG) was performed to assess heart
      rate, QT interval and the presence of any persisting arrhythmia was conducted.
      RESULTS: A total of 279 patients were started on mirabegron. Eight patients
      (2.9%) reported palpitations whilst taking the drug. Two patients with a history
      of palpitations with no history of prolonged QT interval or arrhythmia on ECG
      developed worsening palpitations. The QTc was prolonged in two patients at 0.458
      and 0.441s (QTc <420). Three patients developed chest pain or tightness. The
      palpitations resolved once therapy was stopped and did not result in serious
      adverse events such as hospitalisation. CONCLUSIONS: Palpitations in an
      unselected population have a similar incidence to that demonstrated in previous
      drug trials. Palpitations may be associated with a worsening of cardiovascular
      dysfunction.

PMID- 25756595
TI  - Feasibility of an electrostimulation system treatment for wound healing: a case
      series of patients with chronic ulcers in Barbados.
AB  - Major advances have been made in the development of new therapies for chronic
      wounds. FenzianTM, an electrostimulation system (ES), has been clinically used
      for a variety of conditions. The ES was recently tested in the Barbadian
      population for tolerability and acceptability by asthma patients, with
      encouraging results. Barbados has an estimated 170 people with diabetes having
      some form of lower-extremity amputation annually. Here, we describe a case series
      of 21 chronic ulcer patients with diabetes recruited as inpatients (n = 10) and
      outpatients (n = 11) in a pilot study to evaluate the feasibility and
      acceptability of ES in the Barbadian population. Results showed statistically
      significant improvement among those in the inpatient- versus outpatient-recruited
      group for wound perimeter (P = 0.04), wound surface area (P = 0.03) and wound
      volume (P = 0.08). We also demonstrate that the improvement continued after
      cessation of ES treatment. Participants reported increased levels of pain at the
      end of treatment, and there was no statistically significant change in the
      reported quality of life. Our results showed greater improvements in reduction of
      ulcer size for participants from the inpatient- versus outpatient-recruited
      group.

PMID- 25756596
TI  - Solubility of cellulose in supercritical water studied by molecular dynamics
      simulations.
AB  - The insolubility of cellulose in ambient water and most aqueous systems presents
      a major scientific and practical challenge. Intriguingly though, the dissolution
      of cellulose has been reported to occur in supercritical water. In this study,
      cellulose solubility in ambient and supercritical water of varying density (0.2,
      0.7, and 1.0 g cm(-3)) was studied by atomistic molecular dynamics simulations
      using the CHARMM36 force field and TIP3P water. The Gibbs energy of dissolution
      was determined between a nanocrystal (4 * 4 * 20 anhydroglucose residues) and a
      fully dissociated state using the two-phase thermodynamics model. The analysis of
      Gibbs energy suggested that cellulose is soluble in supercritical water at each
      of the studied densities and that cellulose dissolution is typically driven by
      the entropy gain upon the chain dissociation while simultaneously hindered by the
      loss of solvent entropy. Chain dissociation caused density augmentation around
      the cellulose chains, which improved water-water bonding in low density
      supercritical water whereas the opposite occurred in ambient and high density
      supercritical water. 

PMID- 25756597
TI  - Cancer survivors' experiences of humour while navigating through challenging
      landscapes--a socio-narrative approach.
AB  - AIM: Humour is seen as a health-promoting coping strategy when dealing with life
      stress. The aim is to elucidate how adult cancer survivors experience and
      evaluate the significance of humour in daily life, from diagnosis through their
      entire illness trajectory, and to gain a broader understanding of humour as part
      of stress-coping processes during the experience of cancer as a life-threatening
      illness. METHOD: A socio-narrative approach was chosen to study the humorous
      stories and their use in everyday contexts. Fourteen participants aged 23-83 with
      a variety of experiences across diagnoses, times since diagnosis, prognoses and
      life situations were interviewed. FINDINGS: Participants described humour as
      helpful and utilised its capacity to deal with difficult situations or related
      distress, although fluctuations in the course of the illness coincided with two
      extremes: humour that disappeared and humour that returned. Their use of humour
      was related to three key themes: facing a life-threatening situation,
      togetherness and communication, and living with the situation. CONCLUSION:
      Depending on the aim, humour contributes variously through the stress-coping
      process within the distinctions of emotion-, problem- and meaning-focused coping.
      Humour served to relieve the anxiety burden, enhance problem-solving ability,
      safeguard important relationships, communicate difficult topics, regain identity
      and help significant others to cope, even enabling the richness of life to help
      living with the risk. Humour should be considered as a significant engaging
      coping strategy by which the cancer survivors seek to manage their situation
      throughout the illness trajectory.

PMID- 25756598
TI  - Enhanced photoluminescence and Raman properties of Al-Doped ZnO nanostructures
      prepared using thermal chemical vapor deposition of methanol assisted with heated
      brass.
AB  - Vapor phase transport (VPT) assisted by mixture of methanol and acetone via
      thermal evaporation of brass (CuZn) was used to prepare un-doped and Al-doped
      zinc oxide (ZnO) nanostructures (NSs). The structure and morphology were
      characterized by field emission scanning electron microscopy (FESEM) and x-ray
      diffraction (XRD). Photoluminescence (PL) properties of un-doped and Al-doped ZnO
      showed significant changes in the optical properties providing evidence for
      several types of defects such as zinc interstitials (Zni), oxygen interstitials
      (Oi), zinc vacancy (Vzn), singly charged zinc vacancy (VZn-), oxygen vacancy
      (Vo), singly charged oxygen vacancy (Vo+) and oxygen anti-site defects (OZn) in
      the grown NSs. The Al-doped ZnO NSs have exhibited shifted PL peaks at near band
      edge (NBE) and red luminescence compared to the un-doped ZnO. The Raman
      scattering results provided evidence of Al doping into the ZnO NSs due to peak
      shift from 145 cm-1 to an anomalous peak at 138 cm-1. Presence of enhanced Raman
      signal at around 274 and 743 cm-1 further confirmed Al in ZnO NSs. The enhanced D
      and G band in all Al-doped ZnO NSs shows possible functionalization and doping
      process in ZnO NSs. 

PMID- 25756600
TI  - Long-term selection experiment produces breakdown of horizontal transmissibility
      in parasite with mixed transmission mode.
AB  - Evolutionary transitions from parasitism toward beneficial or mutualistic
      associations may encompass a change from horizontal transmission to (strict)
      vertical transmission. Parasites with both vertical and horizontal transmission
      are amendable to study factors driving such transitions. In a long-term
      experiment, microcosm populations of the protozoan Paramecium caudatum and its
      bacterial parasite Holospora undulata were exposed to three growth treatments,
      manipulating vertical transmission opportunities over ca. 800 host generations.
      In inoculation tests, horizontal transmission propagules produced by parasites
      from a "high-growth" treatment, with elevated host division rates increasing
      levels of parasite vertical transmission, showed a near-complete loss of
      infectivity. A similar reduction was observed for parasites from a treatment
      alternating between high growth and low growth (i.e., low levels of population
      turn-over). Parasites from a low-growth treatment had the highest infectivity on
      all host genotypes tested. Our results complement previous findings of reduced
      investment in horizontal transmission and increased vertical transmissibility of
      high-growth parasites. We explain the loss of horizontal transmissibility by
      epidemiological feedbacks and resistance evolution, reducing the frequency of
      susceptible hosts in the population and thereby decreasing the selective
      advantage of horizontal transmission. This illustrates how environmental
      conditions may push parasites with a mixed transmission mode toward becoming
      vertically transmitted nonvirulent symbionts.

PMID- 25756599
TI  - The evolutionary and functional diversity of classical and lesser-known
      cytoplasmic and organellar translational GTPases across the tree of life.
AB  - BACKGROUND: The ribosome translates mRNA to protein with the aid of a number of
      accessory protein factors. Translational GTPases (trGTPases) are an integral part
      of the 'core set' of essential translational factors, and are some of the most
      conserved proteins across life. This study takes advantage of the wealth of
      available genomic data, along with novel functional information that has come to
      light for a number of trGTPases to address the full evolutionary and functional
      diversity of this superfamily across all domains of life. RESULTS: Through
      sensitive sequence searching combined with phylogenetic analysis, 57 distinct
      subfamilies of trGTPases are identified: 14 bacterial, 7 archaeal and 35
      eukaryotic (of which 21 are known or predicted to be organellar). The results
      uncover the functional evolution of trGTPases from before the last common
      ancestor of life on earth to the current day. CONCLUSIONS: While some trGTPases
      are universal, others are limited to certain taxa, suggesting lineage-specific
      translational control mechanisms that exist on a base of core factors. These
      lineage-specific features may give organisms the ability to tune their
      translation machinery to respond to their environment. Only a fraction of the
      diversity of the trGTPase superfamily has been subjected to experimental
      analyses; this comprehensive classification brings to light novel and overlooked
      translation factors that are worthy of further investigation.

PMID- 25756601
TI  - Structural, thermal, and anti-inflammatory properties of a novel pectic
      polysaccharide from alfalfa (Medicago sativa L.) stem.
AB  - A pectic polysaccharide (APPS) was purified from the cold alkali extract of
      alfalfa stem and characterized to be a rhamnogalacturonan I (RG-I) type pectin
      with the molecular weight of 2.38 * 10(3) kDa and a radius of 123 nm. The primary
      structural analysis indicated that APPS composed of a ->2)-alpha-l-Rhap-(1->4)
      alpha-d-GalpA-(1-> backbone with 12% branching point at C-4 of Rhap forming side
      chains by l-arabinosyl and d-galactosyl oligosaccharide units. Transmission
      electron microscopy (TEM) analysis revealed a primary linear-shaped structure
      with a few branches in its assembly microstructures. The thermal decomposition
      evaluation revealed the stability of APPS with an apparent activation energy (Ea)
      of 226.5 kJ/mol and a pre-exponential factor (A) of 2.10 * 10(25)/s, whereas its
      primary degradation occurred in the temperature range from 215.6 to 328.0 
      degrees C. In addition, APPS showed significant anti-inflammatory effect against
      mRNA expressions of the pro-inflammatory cytokine genes, especially for IL-1beta,
      suggesting its potential utilization in functional foods and dietary supplement
      products.

PMID- 25756602
TI  - Regioselective acceptorless dehydrogenative coupling of N-heterocycles toward
      functionalized quinolines, phenanthrolines, and indoles.
AB  - A new strategy has been developed for the oxidant- and base-free dehydrogenative
      coupling of N-heterocycles at mild conditions. Under the action of an iridium
      catalyst, N-heterocycles undergo multiple sp(3) C?H activation steps, generating
      a nucleophilic enamine that reacts in situ with various electrophiles to give
      highly functionalized products. The dehydrogenative coupling can be cascaded with
      Friedel-Crafts addition, resulting in a double functionalization of the N
      heterocycles. 

PMID- 25756603
TI  - Biodegradable and pH-responsive nanoparticles designed for site-specific delivery
      in agriculture.
AB  - We report the synthesis and characterization of pH-responsive polysuccinimide
      based nanoparticles. Polysuccinimide (PSI), a precursor to biodegradable
      poly(aspartic acid), was synthesized from the condensation of l-aspartic acid and
      subsequently functionalized with primary amines to form random amphiphilic
      copolymers. The copolymers formed stable nanoparticles in aqueous medium via
      nanoprecipitation and were subsequently loaded with a model hydrophobic molecule
      to demonstrate their potential as controlled-release delivery vehicles. It was
      found that above pH 7, the hydrophobic succinimidyl units of the PSI
      nanoparticles hydrolyzed to release encapsulated materials. The release rate
      significantly increased at elevated pH and decreased with an increasing degree of
      functionalization. Finally, plant toxicity studies showed that the polymer
      materials exhibit little to no toxic effects at biologically relevant
      concentrations. 

PMID- 25756604
TI  - Long-term Course of Alzheimer Disease in Patients Treated According to the Dutch
      Dementia Guideline at a Memory Clinic: A "Real-Life" Study.
AB  - INTRODUCTION: There is little knowledge of the long-term course of Alzheimer
      disease (AD) in light of current pharmacological and nonpharmacological
      interventions provided in a "real-life" setting. METHODS: The Frisian Alzheimer's
      Disease Cohort study is a "real-life" study of the course of AD in patients
      (n=576) treated with pharmacological (ie, cholinesterase inhibitors) and
      nonpharmacological (ie, case management, respite care) interventions. Disease
      course was described by changes in cognition (Mini Mental State Examination,
      clock-drawing test) and number of types of professional care applying a repeated
      measures analysis using a marginal model (population-based average model). In
      addition, behavioral and psychological symptoms, and proportions of nursing home
      admissions and deaths were investigated. RESULTS: During 3.5 years, the average
      Mini Mental State Examination decreased from 22.24 to 18.91, the clock-drawing
      test score increased from 3.38 to 4.05, the number of types of professional care
      increased from 0.85 to 2.64, and the patients with behavioral and psychological
      symptoms increased from 29.0% to 70.2%. The proportion of patients admitted to a
      nursing home was 40.8% and 41.0% died. CONCLUSIONS: Cognition and behaviour of AD
      patients deteriorated accompanied with an increase in care-dependency during 3.5
      years. Nevertheless, compared with the precholinesterase inhibitor era, current
      pharmacological and nonpharmacological interventions appear to slow cognitive
      decline, which emphasizes that they seem to have a favorable effect.

PMID- 25756605
TI  - Importance of measures to prevent suicides related to the Great East Japan
      Earthquake among women.

PMID- 25756606
TI  - Clinical pathway to discharge 3 days after colorectal endoscopic submucosal
      dissection.
AB  - BACKGROUND AND AIM: Colorectal endoscopic submucosal dissection (ESD) is a useful
      treatment method; however, no index has been established for time for patient to
      start food ingestion or be discharged after ESD. We investigated the potential of
      a clinical pathway in which patients started food ingestion on day 2 after ESD
      and were discharged on day 3. METHODS: A total of 382 patients underwent
      colorectal ESD between 2006 and 2012. A flow chart of a clinical pathway was
      prepared based on the data obtained, with the aim of shortening hospital stay
      after ESD. RESULTS: Mean duration of postoperative hospital stay in the 382
      patients was 5.3 +/- 1.8 days. The most common cause of extended hospital stay
      was abnormal blood test finding, as detected in 50 patients in group C (n = 131;
      38.2%), followed by careful course observations, as noted in 48 patients in group
      C (n = 131; 36.6%). Regarding procedural accidents as a result of ESD,
      intraoperative perforation occurred in 15 patients (3.9%) and post-ESD bleeding
      in seven patients (1.8%), which extended the hospital stay. Food ingestion was
      started on day 2 when no abnormality was noted during ESD or in physical and
      imaging findings or blood tests on day 1. In the 86 patients who underwent the
      prepared clinical pathway as a validation study, 68 (79.0%) were discharged on
      day 3. Duration of postoperative hospital stay was 3.4 +/- 1.2 days. CONCLUSION:
      Discharge may be possible 3 days after ESD when no abnormalities are noted during
      ESD or on post-ESD day 1.

PMID- 25756607
TI  - Prognostic factors and survival of patients with brain metastasis from breast
      cancer who underwent craniotomy.
AB  - Brain metastasis (BM) in patients with breast cancer is a catastrophic event that
      results in poor prognosis. Identification of prognostic factors associated with
      breast cancer brain metastases (BCBM) could help to identify patients at risk.
      The aim of this study was to assess clinical characteristics, prognostic factors,
      and survival of patients with BCBM who had craniotomy and resection in a series
      of patients treated with modern multimodality therapy. We analyzed 42 patients
      with BCBM who underwent resection. Patients were diagnosed with breast cancer
      between April 1994 and May 2010. Cox proportional hazards regression was selected
      to describe factors associated with time to BM, survival from the date of first
      recurrence, and overall survival (OS). Median age was 51 years (range 24-74).
      Median follow-up was 4.2 years (range 0.6-18.5). The proportion of the biological
      subtypes of breast cancer was ER+/HER2- 25%, ER+/HER2+ 15%, ER-/HER2+ 30%, and ER
      /HER2- 30%. Median OS from the date of primary diagnosis was 5.74 years. Median
      survival after diagnosis of BM was 1.33 years. In multivariate Cox regression
      analyses, stage was the only factor associated with shorter time to the
      development of BM (P = 0.033), whereas age was the only factor associated with
      survival from the date of recurrence (P = 0.027) and with OS (P = 0.037). Stage
      at primary diagnosis correlated with shorter time to the development of BM, while
      age at diagnosis was associated with shorter survival in BCBM. None of the other
      clinical factors had influence on survival. 

PMID- 25756608
TI  - A comparative structure-function analysis of active-site inhibitors of Vibrio
      cholerae cholix toxin.
AB  - Cholix toxin from Vibrio cholerae is a novel mono-ADP-ribosyltransferase (mART)
      toxin that shares structural and functional properties with Pseudomonas
      aeruginosa exotoxin A and Corynebacterium diphtheriae diphtheria toxin. Herein,
      we have used the high-resolution X-ray structure of full-length cholix toxin in
      the apo form, NAD(+) bound, and 10 structures of the cholix catalytic domain (C
      domain) complexed with several strong inhibitors of toxin enzyme activity (NAP,
      PJ34, and the P-series) to study the binding mode of the ligands. A pharmacophore
      model based on the active pose of NAD(+) was compared with the active
      conformation of the inhibitors, which revealed a cationic feature in the side
      chain of the inhibitors that may determine the active pose. Moreover, a
      conformational search was conducted for the missing coordinates of one of the
      main active-site loops (R-loop). The resulting structural models were used to
      evaluate the interaction energies and for 3D-QSAR modeling. Implications for a
      rational drug design approach for mART toxins were derived.

PMID- 25756609
TI  - Tetrapyrrole-based drought stress signalling.
AB  - Tetrapyrroles such as chlorophyll and heme play a vital role in primary plant
      metabolic processes such as photosynthesis and respiration. Over the past
      decades, extensive genetic and molecular analyses have provided valuable insights
      into the complex regulatory network of the tetrapyrrole biosynthesis. However,
      tetrapyrroles are also implicated in abiotic stress tolerance, although the
      mechanisms are largely unknown. With recent reports demonstrating that modified
      tetrapyrrole biosynthesis in plants confers wilting avoidance, a component
      physiological trait to drought tolerance, it is now timely that this pathway be
      reviewed in the context of drought stress signalling. In this review, the
      significance of tetrapyrrole biosynthesis under drought stress is addressed, with
      particular emphasis on the inter-relationships with major stress signalling
      cascades driven by reactive oxygen species (ROS) and organellar retrograde
      signalling. We propose that unlike the chlorophyll branch, the heme branch of the
      pathway plays a key role in mediating intracellular drought stress signalling and
      stimulating ROS detoxification under drought stress. Determining how the
      tetrapyrrole biosynthetic pathway is involved in stress signalling provides an
      opportunity to identify gene targets for engineering drought-tolerant crops. 

PMID- 25756611
TI  - Mapping microbial ecosystems and spoilage-gene flow in breweries highlights
      patterns of contamination and resistance.
AB  - Distinct microbial ecosystems have evolved to meet the challenges of indoor
      environments, shaping the microbial communities that interact most with modern
      human activities. Microbial transmission in food-processing facilities has an
      enormous impact on the qualities and healthfulness of foods, beneficially or
      detrimentally interacting with food products. To explore modes of microbial
      transmission and spoilage-gene frequency in a commercial food-production
      scenario, we profiled hop-resistance gene frequencies and bacterial and fungal
      communities in a brewery. We employed a Bayesian approach for predicting routes
      of contamination, revealing critical control points for microbial management.
      Physically mapping microbial populations over time illustrates patterns of
      dispersal and identifies potential contaminant reservoirs within this
      environment. Habitual exposure to beer is associated with increased abundance of
      spoilage genes, predicting greater contamination risk. Elucidating the genetic
      landscapes of indoor environments poses important practical implications for food
      production systems and these concepts are translatable to other built
      environments. 

PMID- 25756610
TI  - DNA damage shifts circadian clock time via Hausp-dependent Cry1 stabilization.
AB  - The circadian transcriptional repressors cryptochrome 1 (Cry1) and 2 (Cry2)
      evolved from photolyases, bacterial light-activated DNA repair enzymes. In this
      study, we report that while they have lost DNA repair activity, Cry1/2 adapted to
      protect genomic integrity by responding to DNA damage through posttranslational
      modification and coordinating the downstream transcriptional response. We
      demonstrate that genotoxic stress stimulates Cry1 phosphorylation and its
      deubiquitination by Herpes virus associated ubiquitin-specific protease (Hausp,
      a.k.a Usp7), stabilizing Cry1 and shifting circadian clock time. DNA damage also
      increases Cry2 interaction with Fbxl3, destabilizing Cry2. Thus, genotoxic stress
      increases the Cry1/Cry2 ratio, suggesting distinct functions for Cry1 and Cry2
      following DNA damage. Indeed, the transcriptional response to genotoxic stress is
      enhanced in Cry1-/- and blunted in Cry2-/- cells. Furthermore, Cry2-/- cells
      accumulate damaged DNA. These results suggest that Cry1 and Cry2, which evolved
      from DNA repair enzymes, protect genomic integrity via coordinated
      transcriptional regulation. 

PMID- 25756613
TI  - What percentage of patients presenting for routine eye examinations require
      referral for secondary care? A study of referrals from optometrists to
      ophthalmologists.
AB  - BACKGROUND: The aim was to investigate the percentage of asymptomatic patients
      presenting for routine optometric eye examinations that have pathology or
      pathology-related risk factors warranting referral for ophthalmological
      consultation. METHODS: This was a retrospective, cohort case study and the
      inclusion criteria for participants included: (i) the patient presented for
      routine optometric eye care during a specified period of time; (ii) the patient
      was found to have pathology (or showed enough risk of pathology) resulting in
      referral to an ophthalmologist; and (iii) a referral report was received from the
      consulting ophthalmologist stating the diagnosis and the treatment plan. The data
      set was further reviewed to indicate presenting symptoms and patient age. Adult
      patients, ages 20 to 64 years, were reviewed separately; this age group is not
      covered by provincial health services for routine eye care in Nova Scotia. Files
      were obtained from two clinics through an electronic charting program. A database
      was created that included date of referral, clinical reasons for the referral,
      diagnosis and treatment plan. Clinical reasons for referral were extracted from
      the referral letters and reports and sorted into six disease categories: age
      related macular degeneration, cataract, glaucoma, diabetic retinopathy,
      retinopathy and 'other'. RESULTS: The overall referral rate for the combined data
      set was nine per cent for all ages; 2.4 per cent of the overall patients were
      asymptomatic. There was a similar number of asymptomatic patients referred in the
      adult (20 to 64 years) age group compared to all ages (2.5 per cent). CONCLUSION:
      A significant number of patients that present for routine eye examinations
      without any symptoms indicative of ocular disease are subsequently found to have
      a degree of pathology or risk thereof requiring referral for ophthalmological
      consultation. These referrals occur for adults under 64 years as much as for all
      patients of all ages.

PMID- 25756612
TI  - Herpes simplex type 2 virus deleted in glycoprotein D protects against vaginal,
      skin and neural disease.
AB  - Subunit vaccines comprised of glycoprotein D (gD-2) failed to prevent HSV-2
      highlighting need for novel strategies. To test the hypothesis that deletion of
      gD-2 unmasks protective antigens, we evaluated the efficacy and safety of an HSV
      2 virus deleted in gD-2 and complemented allowing a single round of replication
      on cells expressing HSV-1 gD (DeltagD(-/+gD-1)). Subcutaneous immunization of
      C57BL/6 or BALB/c mice with DeltagD(-/+gD1) provided 100% protection against
      lethal intravaginal or skin challenges and prevented latency. DeltagD(-/+gD1)
      elicited no disease in SCID mice, whereas 1000-fold lower doses of wild-type
      virus were lethal. HSV-specific antibodies were detected in serum (titer
      1:800,000) following immunization and in vaginal washes after intravaginal
      challenge. The antibodies elicited cell-mediated cytotoxicity, but little
      neutralizing activity. Passive transfer of immune serum completely protected wild
      type, but not Fcgamma-receptor or neonatal Fc-receptor knock-out mice. These
      studies demonstrate that non-neutralizing Fc-mediated humoral responses confer
      protection and support advancement of this attenuated vaccine. 

PMID- 25756614
TI  - Accumulation dynamics and acute toxicity of silver nanoparticles to Daphnia magna
      and Lumbriculus variegatus: implications for metal modeling approaches.
AB  - Frameworks commonly used in trace metal ecotoxicology (e.g., biotic ligand model
      (BLM) and tissue residue approach (TRA)) are based on the established link
      between uptake, accumulation and toxicity, but similar relationships remain
      unverified for metal-containing nanoparticles (NPs). The present study aimed to
      (i) characterize the bioaccumulation dynamics of PVP-, PEG-, and citrate-AgNPs,
      in comparison to dissolved Ag, in Daphnia magna and Lumbriculus variegatus; and
      (ii) investigate whether parameters of bioavailability and accumulation predict
      acute toxicity. In both species, uptake rate constants for AgNPs were ~ 2-10
      times less than for dissolved Ag and showed significant rank order concordance
      with acute toxicity. Ag elimination by L. variegatus fitted a 1-compartment loss
      model, whereas elimination in D. magna was biphasic. The latter showed
      consistency with studies that reported daphnids ingesting NPs, whereas L.
      variegatus biodynamic parameters indicated that uptake and efflux were primarily
      determined by the bioavailability of dissolved Ag released by the AgNPs. Thus,
      principles of BLM and TRA frameworks are confounded by the feeding behavior of D.
      magna where the ingestion of AgNPs perturbs the relationship between tissue
      concentrations and acute toxicity, but such approaches are applicable when
      accumulation and acute toxicity are linked to dissolved concentrations. The
      uptake rate constant, as a parameter of bioavailability inclusive of all
      available pathways, could be a successful predictor of acute toxicity.

PMID- 25756615
TI  - Peptides from the inside of the antibodies are active against infectious agents
      and tumours.
AB  - Synthetic peptides, representative of sequences related to the complementarity
      determining regions and constant region of antibodies, proved to exert in vitro,
      ex vivo and/or in vivo antimicrobial, antiviral, anti-tumour and/or
      immunomodulatory activities, conceivably mediated by different mechanisms of
      action and regardless of the specificity and isotype of the belonging
      immunoglobulin. Antibody-derived peptides can show intrinsic properties of self
      aggregation in beta structures, able to assemble on molecular targets and
      dissociate spontaneously, leading to the formation of hydrogels. Whilst the self
      assembled state may provide protection against proteases and the slow kinetic of
      dissociation assures a release of the active form over time, the receptor
      affinity is responsible for targeted delivery. Peptides derived from single amino
      acid substitution of bioactive antibody fragments, adopted as surrogates of
      natural point mutations, displayed further differential biological activities.
      Overall, these observations allow to envisage that antibodies could represent an
      unlimited source of new anti-infective and anti-tumour peptides.

PMID- 25756616
TI  - Bidentate, monoanionic auxiliary-directed functionalization of carbon-hydrogen
      bonds.
AB  - In recent years, carbon-hydrogen bond functionalization has evolved from an
      organometallic curiosity to a tool used in mainstream applications in the
      synthesis of complex natural products and drugs. The use of C-H bonds as a
      transformable functional group is advantageous because these bonds are the most
      abundant functionality in organic molecules. One-step conversion of these bonds
      to the desired functionality shortens synthetic pathways, saving reagents,
      solvents, and labor. Less chemical waste is generated as well, showing that this
      chemistry is environmentally beneficial. This Account describes the development
      and use of bidentate, monoanionic auxiliaries for transition-metal-catalyzed C-H
      bond functionalization reactions. The chemistry was initially developed to
      overcome the limitations with palladium-catalyzed C-H bond functionalization
      assisted by monodentate directing groups. By the use of electron-rich bidentate
      directing groups, functionalization of unactivated sp(3) C-H bonds under
      palladium catalysis has been developed. Furthermore, a number of abundant base
      metal complexes catalyze functionalization of sp(2) C-H bonds. At this point,
      aminoquinoline, picolinic acid, and related compounds are among the most used and
      versatile directing moieties in C-H bond functionalization chemistry. These
      groups facilitate catalytic functionalization of sp(2) and sp(3) C-H bonds by
      iron, cobalt, nickel, copper, ruthenium, rhodium, and palladium complexes.
      Exceptionally general reactivity is observed, enabling, among other
      transformations, direct arylation, alkylation, fluorination, sulfenylation,
      amination, etherification, carbonylation, and alkenylation of carbon-hydrogen
      bonds. The versatility of these auxilaries can be attributed to the following
      factors. First, they are capable of stabilizing high oxidation states of
      transition metals, thereby facilitating the C-H bond functionalization step.
      Second, the directing groups can be removed, enabling their use in synthesis and
      functionalization of natural products and medicinally relevant substances. While
      the development of these directing groups presents a significant advance, several
      limitations of this methodology are apparent. The use of expensive second-row
      transition metal catalysts is still required for efficient sp(3) C-H bond
      functionalization. Furthermore, the need to install and subsequently remove the
      relatively expensive directing group is a disadvantage. 

PMID- 25756617
TI  - How the creative use of analogies can shape medical practice.
AB  - Analogical reasoning is central to medical progress, and is either creative or
      conservative. According to Hofmann et al., conservative analogy relates concepts
      from old technology to new technologies with emphasis on preservation of
      comprehension and conduct. Creative analogy however brings new understanding to
      new technology, brings similarities existing in the source domain to a target
      domain where they previously had no bearing, and imports something entirely
      different from the content of the analogy itself. I defend the claim that while
      conservative analogies are useful by virtue of being comfortable to use from
      familiarity and experience, and are more easily accepted by society, they only
      lead to incremental advances in medicine. However, creative analogies are more
      exciting and productive because they generate previously unexpected associations
      across widely separated domains, emphasize relations over physical similarities,
      and structure over superficiality. I use kidney transplantation and anti
      rejection medication development as an exemplar of analogical reasoning used to
      improve medical practice. Anti-rejection medication has not helped highly
      sensitized patients because of their propensity to rejecting most organs. I
      outline how conservative analogical reasoning led to anti-rejection medication
      development, but creative analogical reasoning helped highly sensitized and blood
      type incompatible patients through domino transplants, by which they obtain a
      kidney to which they are not sensitized. Creative analogical reasoning is more
      likely than conservative analogical reasoning to lead to revolutionary progress.
      While these analogies overlap and creative analogies eventually become
      conservative, progress is best facilitated by combining conservative and creative
      analogical reasoning. 

PMID- 25756618
TI  - Ionic conductivity of beta-cyclodextrin-polyethylene-oxide/alkali-metal-salt
      complex.
AB  - Highly conductive, crystalline, polymer electrolytes, beta-cyclodextrin (beta-CD)
      polyethylene oxide (PEO)/LiAsF6 and beta-CD-PEO/NaAsF6 , were prepared through
      supramolecular self-assembly of PEO, beta-CD, and LiAsF6 /NaAsF6 . The assembled
      beta-CDs form nanochannels in which the PEO/X(+) (X=Li, Na) complexes are
      confined. The nanochannels provide a pathway for directional motion of the alkali
      metal ions and, at the same time, separate the cations and the anions by size
      exclusion. 

PMID- 25756619
TI  - The long and winding road to uncertainty: the link between spatial distance and
      feelings of uncertainty.
AB  - Construal Level Theory (CLT) [1] defines psychological distance as any object,
      event, or person that cannot be experienced by the self in the here and now. The
      goal of the present research was to demonstrate that feelings of uncertainty are
      closely linked to the concept of psychological distance. Two experiments tested
      the assumption that spatial distance and uncertainty are bidirectionally related.
      In the first experiment, we show that perceived spatial distance leads to a
      feeling of uncertainty. The second experiment revealed that a feeling of
      uncertainty leads to a perception of greater distance. By demonstrating that
      distance is closely tied to uncertainty, the present research extends previous
      research on both distance and uncertainty by incorporating previously unexplained
      findings within CLT. Implications of these findings such as the role of
      uncertainty within CLT are discussed. 

PMID- 25756620
TI  - Bacillusin A, an Antibacterial Macrodiolide from Bacillus amyloliquefaciens
      AP183.
AB  - Bioassay-guided fractionation of the organic extracts of a Bacillus
      amyloliquefaciens strain (AP183) led to the discovery of a new macrocyclic
      polyene antibiotic, bacillusin A (1). Its structure was assigned by
      interpretation of NMR and MS spectroscopic data as a novel macrodiolide composed
      of dimeric 4-hydroxy-2-methoxy-6-alkenylbenzoic acid lactones with conjugated
      pentaene-hexahydroxy polyketide chains. Compound 1 showed potent antibacterial
      activities against methicillin-resistant Staphylococcus aureus and vancomycin
      resistant Enterococcus faecium with minimum inhibitory concentrations in a range
      of 0.6 to 1.2 MUg/mL. The biosynthetic significance of this unique class of
      antibiotic compounds is briefly discussed. 

PMID- 25756621
TI  - Voxel-based texture analysis of the brain.
AB  - This paper presents a novel voxel-based method for texture analysis of brain
      images. Texture analysis is a powerful quantitative approach for analyzing voxel
      intensities and their interrelationships, but has been thus far limited to
      analyzing regions of interest. The proposed method provides a 3D statistical map
      comparing texture features on a voxel-by-voxel basis. The validity of the method
      was examined on artificially generated effects as well as on real MRI data in
      Alzheimer's Disease (AD). The artificially generated effects included
      hyperintense and hypointense signals added to T1-weighted brain MRIs from 30
      healthy subjects. The AD dataset included 30 patients with AD and 30 age/sex
      matched healthy control subjects. The proposed method detected artificial effects
      with high accuracy and revealed statistically significant differences between the
      AD and control groups. This paper extends the usage of texture analysis beyond
      the current region of interest analysis to voxel-by-voxel 3D statistical mapping
      and provides a hypothesis-free analysis tool to study cerebral pathology in
      neurological diseases. 

PMID- 25756622
TI  - Assessment of initial serum vancomycin trough concentrations and their
      association with initial empirical weight-based vancomycin dosing and development
      of nephrotoxicity in children: a multicenter retrospective study.
AB  - STUDY OBJECTIVES: To determine whether a relationship exists between initial
      serum vancomycin trough concentrations and initial empirical vancomycin dose,
      patient weight, and patient age, and to determine the risks for vancomycin
      associated nephrotoxicity in pediatric patients stratified by hospital setting.
      DESIGN: Stepwise linear and multinomial logistic regression analysis of
      retrospectively collected data. SETTING: Two geographically distinct children's
      tertiary care medical centers. PATIENTS: A total of 316 pediatric patients
      without preexisting renal dysfunction who were managed outside of the neonatal
      intensive care unit and were treated with at least 3 doses of vancomycin for gram
      positive bacterial infections and had at least one serum vancomycin trough
      concentration between January 1, 2008, and July 31, 2010. MEASUREMENTS AND MAIN
      RESULTS: Elevated vancomycin trough concentrations had no statistically
      significant relationship with initial empirical vancomycin dosing across all
      hospital settings. Serum vancomycin trough concentrations (lower than 15 mg/L or
      15-20 mg/L) were not associated with increased risk of nephrotoxicity.
      Concomitant nephrotoxic agents, however, including loop diuretics, vasopressors,
      angiotensin-converting enzyme (ACE) inhibitors, and nonsteroidal antiinflammatory
      drugs (NSAIDs) were significantly associated with the development of
      nephrotoxicity in medical-surgical and intensive care patients. Based on this
      analysis, use of loop diuretics and vasopressors increased the odds of developing
      nephrotoxicity (odds ratio [OR] 42.8 [p=0.001] and 18.4 [p=0.02], respectively).
      Use of NSAIDS and ACE inhibitors also increased the odds of developing
      nephrotoxicity (OR 18.6 [p=0.02] and 4.7 [p=0.03], respectively). CONCLUSION: No
      significant associations were found between initial empirical weight-based
      vancomycin dosing or elevated serum trough concentrations and development of
      nephrotoxicity in children; rather, nephrotoxicity was associated with
      combination therapy with vancomycin and other potentially nephrotoxic agents.

PMID- 25756624
TI  - Synchrotron-based X-ray fluorescence microscopy in conjunction with
      nanoindentation to study molecular-scale interactions of phenol-formaldehyde in
      wood cell walls.
AB  - Understanding and controlling molecular-scale interactions between adhesives and
      wood polymers are critical to accelerate the development of improved adhesives
      for advanced wood-based materials. The submicrometer resolution of synchrotron
      based X-ray fluorescence microscopy (XFM) was found capable of mapping and
      quantifying infiltration of Br-labeled phenol-formaldehyde (BrPF) into wood cell
      walls. Cell wall infiltration of five BrPF adhesives with different average
      molecular weights (MWs) was mapped. Nanoindentation on the same cell walls was
      performed to assess the effects of BrPF infiltration on cell wall hygromechanical
      properties. For the same amount of weight uptake, lower MW BrPF adhesives were
      found to be more effective at decreasing moisture-induced mechanical softening.
      This greater effectiveness of lower MW phenolic adhesives likely resulted from
      their ability to more intimately associate with water sorption sites in the wood
      polymers. Evidence also suggests that a BrPF interpenetrating polymer network
      (IPN) formed within the wood polymers, which might also decrease moisture
      sorption by mechanically restraining wood polymers during swelling. 

PMID- 25756623
TI  - Evidence for intermolecular interactions between the intracellular domains of the
      arabidopsis receptor-like kinase ACR4, its homologs and the Wox5 transcription
      factor.
AB  - Arabidopsis CRINKLY4 (ACR4) is a receptor-like kinase (RLK) involved in the
      global development of the plant. The Arabidopsis genome encodes four homologs of
      ACR4 that contain sequence similarity and analogous architectural elements to
      ACR4, termed Arabidopsis CRINKLY4 Related (AtCRRs) proteins. Additionally, a
      signaling module has been previously proposed including a postulated peptide
      ligand, CLE40, the ACR4 RLK, and the WOX5 transcription factor that engage in a
      possible feedback mechanism controlling stem cell differentiation. However,
      little biochemical evidence is available to ascertain the molecular aspects of
      receptor heterodimerization and the role of phosphorylation in these
      interactions. Therefore, we have undertaken an investigation of the in vitro
      interactions between the intracellular domains (ICD) of ACR4, the CRRs and WOX5.
      We demonstrate that interaction can occur between ACR4 and all four CRRs in the
      unphosphorylated state. However, phosphorylation dependency is observed for the
      interaction between ACR4 and CRR3. Furthermore, sequence analysis of the ACR4
      gene family has revealed a conserved 'KDSAF' motif that may be involved in
      protein-protein interactions among the receptor family. We demonstrate that
      peptides harboring this conserved motif in CRR3 and CRK1are able to bind to the
      ACR4 kinase domain. Our investigations also indicate that the ACR4 ICD can
      interact with and phosphorylate the transcription factor WOX5. 

PMID- 25756625
TI  - Endoscopic obstruction in rectal cancers: survival and recurrence patterns
      following curative surgery.
AB  - BACKGROUND: It is controversial whether preoperative obstruction in rectal
      cancers can affect prognosis or influence recurrence patterns. We investigated
      the association between endoscopic obstruction with survival and recurrence
      patterns in patients with locally advanced rectal cancers. MATERIALS AND METHODS:
      An observational study and multivariate analysis were conducted to identify
      determinants of survival and to compare recurrence patterns between patients with
      obstructive or nonobstructive tumors after curative resection. Endoscopic
      obstruction was defined as a luminal obstruction of the rectum severe enough to
      prevent the colonoscope from passing beyond the tumor. RESULTS: Cancer was
      obstructive in 91 patients (16.8%) and nonobstructive in 452 (83.2%). Median
      follow-up was 50 (range, 3-161) months. Local recurrence occurred in 17 patients
      (14 nonobstructed [5.4%] and 3obstructed [5.5%]; P=1.0) and systemic recurrence
      in 83 (62 nonobstructed [23.8%] and 21 obstructed [38.2%]; P=.042]). Endoscopic
      obstruction was a significant prognostic factor in stage III rectal cancers
      (P=.001) but not in stage II tumors. The multivariate analysis showed that
      endoscopic obstruction was an independent prognostic factor for overall survival,
      but not for disease-free survival, in patients with stage III rectal cancers.
      Endoscopic obstruction was associated with multiple-site systemic recurrence that
      was unsalvageable (salvageable surgery, 24 nonobstructed [40%] and 2 obstructed
      [10%]; P=.014). CONCLUSIONS: Endoscopic obstruction in patients with stage III
      rectal cancer predicted worse overall survival and was associated with multiple
      site systemic recurrence.

PMID- 25756626
TI  - Pharmacologic treatments for borderline personality disorder.

PMID- 25756627
TI  - Supported employment over the long term: from effectiveness to sustainability.

PMID- 25756628
TI  - The other side of bipolar disorder.

PMID- 25756629
TI  - Smoking cessation in men and women.

PMID- 25756630
TI  - The MATRICS consensus cognitive battery: what we know 6 years later.

PMID- 25756631
TI  - Pulmonary embolism in a psychiatric patient.

PMID- 25756632
TI  - Medically unexplained somatic symptoms: diagnostic and treatment issues on the
      Indian subcontinent.

PMID- 25756633
TI  - The Trans-Allegheny Lunatic Asylum, then and now.

PMID- 25756634
TI  - The impact of benzodiazepine management in the randomized, double-blind
      evaluation of D-cycloserine or alprazolam combined with virtual reality exposure
      therapy.

PMID- 25756635
TI  - Response to Granoff.

PMID- 25756636
TI  - Possible negative effects of extinction learning on outcomes for patients
      receiving exposure therapy.

PMID- 25756637
TI  - Response to Smith.

PMID- 25756638
TI  - Correction.

PMID- 25756645
TI  - Two-level spatial modulation of vibronic conductance in conjugated
      oligophenylenes on boron nitride.
AB  - Intramolecular current-induced vibronic excitations are reported in highly
      ordered monolayers of quaterphenylene dicarbonitriles at an electronically
      patterned boron nitride on copper platform (BN/Cu(111)). A first level of
      spatially modulated conductance at the nanometer-scale is induced by the
      substrate. Moreover, a second level of conductance variations at the molecular
      level is found. Low temperature scanning tunneling microscopy studies in
      conjunction with molecular dynamics calculations reveal collective amplification
      of the molecule's interphenylene torsion angles in the monolayer. Librational
      modes influencing these torsion angles are identified as initial excitations
      during vibronic conductance. Density functional theory is used to map phenylene
      breathing modes and other vibrational excitations that are suggested to be at the
      origin of the submolecular features during vibronic conductance. 

PMID- 25756646
TI  - Detection of ethanol in alcoholic beverages or vapor phase using fluorescent
      molecules embedded in a nanofibrous polymer.
AB  - An alcohol sensor was developed using the solid-state fluorescence emission of
      terphenyl-ol (TPhOH) derivatives. Admixtures of TPhOH and sodium carbonate
      exhibited bright sky-blue fluorescence in the solid state upon addition of small
      quantities of ethanol. A series of terphenol derivatives was synthesized, and the
      effects of solvent polarities and the structures of these pi-conjugated systems
      on their fluorescence were systematically investigated by using fluorescence
      spectroscopy. In particular, pi-extended TPhOHs and TPhOHs containing electron
      withdrawing groups exhibited significant solvatochromism, and fluorescence colors
      varied from blue to red. Detection of ethanol contents in alcohol beverages
      (detection limit ~ 5 v/v %) was demonstrated using different TPhOHs revealing the
      effect of molecular structure on sensing properties. Ethanol contents in
      alcoholic beverages could be estimated from the intensity of the fluorescence
      elicited from the TPhOHs. Moreover, when terphenol and Na2CO3 were combined with
      a water-absorbent polymer, ethanol could be detected at lower concentrations.
      Detection of ethanol vapor (8 v/v % in air) was also accomplished using a
      nanofibrous polymer scaffold as the immobilized sensing film. 

PMID- 25756648
TI  - Discrepancies in composition and biological effects of different formulations of
      chondroitin sulfate.
AB  - Osteoarthritis is a common, progressive joint disease, and treatments generally
      aim for symptomatic improvement. However, SYmptomatic Slow-Acting Drugs in
      Osteoarthritis (SYSADOAs) not only reduce joint pain, but slow structural disease
      progression. One such agent is chondroitin sulfate-a complex, heterogeneous
      polysaccharide. It is extracted from various animal cartilages, thus has a wide
      range of molecular weights and different amounts and patterns of sulfation.
      Chondroitin sulfate has an excellent safety profile, and although various meta
      analyses have concluded that it has a beneficial effect on symptoms and
      structure, others have concluded little or no benefit. This may be due, at least
      partly, to variations in the quality of the chondroitin sulfate used for a
      particular study. Chondroitin sulfate is available as pharmaceutical- and
      nutraceutical-grade products, and the latter have great variations in
      preparation, composition, purity and effects. Moreover, some products contain a
      negligible amount of chondroitin sulfate and among samples with reasonable
      amounts, in vitro testing showed widely varying effects. Of importance, although
      some showed anti-inflammatory effects, others demonstrated weak effects, and some
      instances were even pro-inflammatory. This could be related to contaminants,
      which depend on the origin, production and purification process. It is therefore
      vitally important that only pharmaceutical-grade chondroitin sulfate be used for
      treating osteoarthritis patients. 

PMID- 25756647
TI  - Association of symptoms and severity of rift valley fever with genetic
      polymorphisms in human innate immune pathways.
AB  - BACKGROUND: Multiple recent outbreaks of Rift Valley Fever (RVF) in Africa,
      Madagascar, and the Arabian Peninsula have resulted in significant morbidity,
      mortality, and financial loss due to related livestock epizootics. Presentation
      of human RVF varies from mild febrile illness to meningoencephalitis, hemorrhagic
      diathesis, and/or ophthalmitis with residual retinal scarring, but the
      determinants for severe disease are not understood. The aim of the present study
      was to identify human genes associated with RVF clinical disease in a high-risk
      population in Northeastern Province, Kenya. METHODOLOGY/PRINCIPAL FINDINGS: We
      conducted a cross-sectional survey among residents (N = 1,080; 1-85 yrs) in 6
      villages in the Sangailu Division of Ijara District. Participants completed
      questionnaires on past symptoms and exposures, physical exam, vision testing, and
      blood collection. Single nucleotide polymorphism (SNP) genotyping was performed
      on a subset of individuals who reported past clinical symptoms consistent with
      RVF and unrelated subjects. Four symptom clusters were defined:
      meningoencephalitis, hemorrhagic fever, eye disease, and RVF-not otherwise
      specified. SNPs in 46 viral sensing and response genes were investigated.
      Association was analyzed between SNP genotype, serology and RVF symptom clusters.
      The meningoencephalitis symptom phenotype cluster among seropositive patients was
      associated with polymorphisms in DDX58/RIG-I and TLR8. Having three or more RVF
      related symptoms was significantly associated with polymorphisms in TICAM1/TRIF,
      MAVS, IFNAR1 and DDX58/RIG-I. SNPs significantly associated with eye disease
      included three different polymorphisms TLR8 and hemorrhagic fever symptoms
      associated with TLR3, TLR7, TLR8 and MyD88. CONCLUSIONS/SIGNIFICANCE: Of the 46
      SNPs tested, TLR3, TLR7, TLR8, MyD88, TRIF, MAVS, and RIG-I were repeatedly
      associated with severe symptomatology, suggesting that these genes may have a
      robust association with RVFV-associated clinical outcomes. Studies of these and
      related genetic polymorphisms are warranted to advance understanding of RVF
      pathogenesis.

PMID- 25756649
TI  - Screening antitumor bioactive fraction from Sauromatum giganteum (Engl.) Cusimano
      & Hett and sensitive cell lines with the serum pharmacology method and
      identification by UPLC-TOF-MS.
AB  - Sauromatum giganteum (Engl.) Cusimano & Hett Tuber are used in Chinese folklore
      medicine for treatment of neoplasms. However, the claim has not been
      scientifically validated. The aim of the study is to screen the antitumor
      bioactive fraction of Sauromatum giganteum (Engl.) Cusimano & Hett Tuber and
      sensitive tumor cell lines using a cytotoxicity assay in vitro and tumor
      transplantation method in vivo, to support its use in folk medicine. The
      petroleum ether fraction, chloroform fraction, ethyl acetate fraction, n-butanol
      fraction and water fraction were successively extracted by turn by the maceration
      under reflux assay. Screening of antitumor bioactive fraction and sensitive cell
      lines were measured by MTT assay and the serum pharmacology method, and in vivo
      the antitumor activities of the active fraction was evaluated by using S180 or
      H22 tumor-bearing mice model and Kunming mice. The active constituents of ethyl
      acetate fraction of Sauromatum giganteum (Engl.) Cusimano & Hett were
      characterized by UPLC-TOF-MS. Compared with control groups, mice serum containing
      ethyl acetate fraction had a inhibition effect on SMMC-7721 cell, SGC-7901 cell,
      MCF-7 cell, HeLa cell, A549 cell, HT-29, and MDA-MB-231, respectively, but mice
      serum containing other four fractions had no different with that of control
      group. The inhibition capabilities of mice serum containing ethyl acetate
      fraction on the seven cell lines in descending order is SGC-7901 > SMMC-7721 >
      MCF-7 > HT-29 > A549 > HeLa > MDA-MB-231. In vivo the inhibition rate of 106,
      318, 954 mg/kg.d ethyl acetate fraction dry extract to sarcoma S180 is 15.22%,
      26.15% and 40.24%, respectively, and life prolonging rate to hepatoma H22 is
      33.61%, 40.16% and 55.74%. A total of 14 compounds were identified in the ethyl
      acetate fraction of Sauromatum giganteum (Engl.) Cusimano & Hett. The results of
      the experimental studies proved the antitumor activity of Sauromatum giganteum
      (Engl.) Cusimano & Hett and supported the traditional use of this plant. These
      data indicate the potential for the use of ethyl acetate fraction of Sauromatum
      giganteum (Engl.) Cusimano & Hett Tuber in tumor therapy, anti-tumor activity on
      cancer cell line in descending order is SGC-7901 > SMMC-7721 > MCF-7 > HT-29 >
      A549 > HeLa > MDA-MB-231. 

PMID- 25756650
TI  - LC-ESI-MS/MS analysis and pharmacokinetics of GP205, an innovative potent
      macrocyclic inhibitor of hepatitis C virus NS3/4A protease in rats.
AB  - A high-throughput, sensitive and specific LC-ESI-MS/MS method was established for
      the quantitative determination of GP205, a potent inhibitor of hepatitis C virus
      NS3/4A protease, in rat. The analyte was isolated from 25 MUL plasma sample by 96
      well LLE. Good linearity was achieved within the concentration range of 2-5000
      ng/mL (r2 > 0.996). The intra- and inter-day precision was less than 10%. The
      accuracy ranged from 0.8% to 5.5% for GP205 in quality control samples at three
      levels. GP205 was stable during the analysis and the storage period. The method
      was successfully applied to pharmacokinetic studies of GP205 in Sprague-Dawley
      rats. The pharmacokinetic profiles of GP205 at three dose levels with oral
      administration and one dose level with intravenous administration were
      successfully studied for the first time in SD rats, respectively. After single
      oral administration of GP205 at the doses of 2.5, 5, 10 mg/kg, respectively, Cmax
      and AUC0-tau were proportional to the doses given. The absolute bioavailability
      was estimated as 34% based on the AUCs of oral administration at the dose of 5
      mg/kg and intravenous administration at the dose of 1 mg/kg. The data presented
      in this study provides useful information for further study for GP205. 

PMID- 25756653
TI  - Percolating transport and the conductive scaling relationship in lamellar block
      copolymers under confinement.
AB  - The topology and transport behavior of the lamellar morphology self-assembled by
      block copolymers in thin films are shown to depend on the length scale over which
      they are characterized and can be described by percolation in a network under
      confinement. Gold nanowires replicating the lamellar morphology were fabricated
      via self-assembled poly(styrene-block-methyl methacrylate) thin films and a lift
      off pattern transfer process. The lamellar morphology exhibits long-range
      connectivity (macroscopic scale); however, characterization of electrical
      conduction over confined areas (5-500 MUm) demonstrates a discrete probability of
      disconnection that arises due to the underlying network structure and a lack of
      self-similarity at these microscale dimensions. In particular, it is proved that
      the lamellar network morphology under confinement has a conductance that is
      nonlinear with channel length or width. The experimental results are discussed in
      terms of percolation theory, and a simple, two-dimensional Monte Carlo model is
      shown to predict the key trends in the network topology and conductance in
      lamellar block copolymers, including the dependencies on composition, extent of
      spatial confinement, and confinement geometry. These results highlight the need
      to exquisitely control or engineer the self-assembled nanostructured pathways
      formed by block copolymers to ensure consistent device performance for any
      application that depends upon percolating material, ionic, or electrical
      transport, especially when confined in any dimension. It is also concluded that
      the two most promising approaches for enhancing conductivity in block copolymer
      materials may be achieved either at the limits of (1) perfectly oriented, single
      crystalline or (2) high defect density, polycrystalline microphase separated
      morphologies and that nanostructured systems with intermediate defect densities
      would be detrimental to transport in confined systems. 

PMID- 25756651
TI  - Bioavailability enhancement of paclitaxel via a novel oral drug delivery system:
      paclitaxel-loaded glycyrrhizic acid micelles.
AB  - Paclitaxel (PTX, taxol), a classical antitumor drug against a wide range of
      tumors, shows poor oral bioavailability. In order to improve the oral
      bioavailability of PTX, glycyrrhizic acid (GA) was used as the carrier in this
      study. This was the first report on the preparation, characterization and the
      pharmacokinetic study in rats of PTX-loaded GA micelles The PTX-loaded micelles,
      prepared with ultrasonic dispersion method, displayed small particle sizes and
      spherical shapes. Differential scanning calorimeter (DSC) thermograms indicated
      that PTX was entrapped in the GA micelles and existed as an amorphous state. The
      encapsulation efficiency was about 90%, and the drug loading rate could reach up
      to 7.90%. PTX-loaded GA micelles displayed a delayed drug release compared to
      Taxol in the in vitro release experiment. In pharmacokinetic study via oral
      administration, the area under the plasma concentration-time curve (AUC0->24 h)
      of PTX-loaded GA micelles was about six times higher than that of Taxol (p <
      0.05). The significant oral absorption enhancement of PTX from PTX-loaded GA
      micelles could be largely due to the increased absorption in jejunum and colon
      intestine. All these results suggested that GA would be a promising carrier for
      the oral delivery of PTX. 

PMID- 25756654
TI  - Exact learning of RNA energy parameters from structure.
AB  - We consider the problem of exact learning of parameters of a linear RNA energy
      model from secondary structure data. A necessary and sufficient condition for
      learnability of parameters is derived, which is based on computing the convex
      hull of union of translated Newton polytopes of input sequences. The set of
      learned energy parameters is characterized as the convex cone generated by the
      normal vectors to those facets of the resulting polytope that are incident to the
      origin. In practice, the sufficient condition may not be satisfied by the entire
      training data set; hence, computing a maximal subset of training data for which
      the sufficient condition is satisfied is often desired. We show that the problem
      is NP-hard in general for an arbitrary dimensional feature space. Using a
      randomized greedy algorithm, we select a subset of RNA STRAND v2.0 database that
      satisfies the sufficient condition for separate A-U, C-G, G-U base pair counting
      model. The set of learned energy parameters includes experimentally measured
      energies of A-U, C-G, and G-U pairs; hence, our parameter set is in agreement
      with the Turner parameters. 

PMID- 25756655
TI  - Mechanical properties of mosquito nets in the context of hernia repair.
AB  - The paper deals with issue of applying mosquito nets as implants in hernia
      repair, which have already been used in resource-poor developing countries.
      Uniaxial tensile tests have been conducted on polyester mosquito meshes in two
      orthogonal directions. Non-linear elastic constitutive laws parameters have been
      identified to be applied in dense net material models. Mechanical performance of
      tested mosquito nets has been compared with properties of commercial implants
      used in treatment of hernia and with properties of human tissue. This study
      contributes to mechanical knowledge of hernia repair issue by investigation of
      cheaper alternative to commercial implants.

PMID- 25756656
TI  - Structural defects lead to dynamic entrapment in cardiac electrophysiology.
AB  - Biological networks are typically comprised of many parts whose interactions are
      governed by nonlinear dynamics. This potentially imbues them with the ability to
      support multiple attractors, and therefore to exhibit correspondingly distinct
      patterns of behavior. In particular, multiple attractors have been demonstrated
      for the electrical activity of the diseased heart in situations where
      cardioversion is able to convert a reentrant arrhythmia to a stable normal
      rhythm. Healthy hearts, however, are typically resilient to abnormal rhythms.
      This raises the question as to how a healthy cardiac cell network must be altered
      so that it can support multiple distinct behaviors. Here we demonstrate how
      anatomic defects can give rise to multi-stability in the heart as a function of
      the electrophysiological properties of the cardiac tissue and the timing of
      activation of ectopic foci. This leads to a form of hysteretic behavior, which we
      call dynamic entrapment, whereby the heart can become trapped in aberrant
      attractor as a result of a transient change in tissue properties. We show that
      this can lead to a highly inconsistent relationship between clinical symptoms and
      underlying pathophysiology, which raises the possibility that dynamic entrapment
      may underlie other forms of chronic idiopathic illness. 

PMID- 25756657
TI  - Smartphone-Derived Heart-Rate Variability and Training Load in a Women's Soccer
      Team.
AB  - PURPOSE: This study evaluated the 7-d mean and coefficient of variation (CV) of
      supine and standing ultrashort log-transformed root mean square of successive R-R
      intervals multiplied by 20 (lnRMSSDx20) obtained with a smartphone application
      (app) in response to varying weekly training load (TL). In addition, the authors
      aimed to determine if these values could be accurately assessed in as few as 5 or
      3 d/wk. METHODS: Nine women from a college soccer team performed daily heart-rate
      variability measures with an app in supine and standing positions over 3 wk of
      moderate, high, and low TL. The mean and CV over 7, 5, and 3 d were compared
      within and between weeks. RESULTS: The 5- and 3-d measures within each week
      provided very good to nearly perfect intraclass correlations (ICCs .74-.99) with
      typical errors ranging from 0.64 to 5.65 when compared with the 7-d criteria. The
      7, 5, and 3-d supine CV and the 7-day standing CV were moderately lower during
      the low-load than the high-load week (P .003-.045, effect sizes 0.86-0.92), with
      no significant changes occurring in the other measures. CONCLUSION: This study
      supports the use of the mean and CV of lnRMSSD measured across at least 5 d for
      reflecting weekly values. The supine lnRMSSDx20 CV as measured across 7, 5, and 3
      d was the most sensitive marker to the changes in TL in the 3-wk period.

PMID- 25756659
TI  - WITHDRAWN: Steroids, radiotherapy, chemotherapy and stents for superior vena
      caval obstruction in carcinoma of the bronchus.

PMID- 25756658
TI  - Identification of the base-pairing requirements for repression of hctA
      translation by the small RNA IhtA leads to the discovery of a new mRNA target in
      Chlamydia trachomatis.
AB  - The non-coding small RNA, IhtA expressed by the obligate intracellular human
      pathogen Chlamydia trachomatis modulates the translation of HctA, a key protein
      involved in replicative to infectious cell type differentiation. Using a
      combination of bioinformatics and mutagenesis we sought to identify the base
      pairing requirement for functional repression of HctA protein expression, with an
      eye to applying our findings towards the identification of additional targets.
      IhtA is predicted to fold into a three stem:loop structure. We found that loop 1
      occludes the initiation codon of hctA, while loop 2 and 3 are not required for
      function. This 7 nucleotide region forms G/C rich interactions surrounding the
      AUG of hctA. Two additional genes in the chlamydial genome, CTL0322 and CTL0097,
      contained some elements of the hctA:IhtA recognition sequence. The mRNA of both
      CTL0322and CTL0097 interacted with IhtA in vitro as measured by biolayer
      interferometry. However, using a CheZ reporter expression system, IhtA only
      inhibited the translation of CTL0322. The proposed IhtA recognition site in the
      CTL0322 message contains significant G/C base pairing on either side of the
      initiation codon while CTL0097 only contains G/C base pairing 3' to the AUG
      initiation codon. These data suggest that as the functional interacting region is
      only 6-7nt in length that full translation repression is dependent on the degree
      of G/C base pairing. Additionally our results indicate that IhtA may regulate
      multiple mRNAs involved in the chlamydial infectious cycle. 

PMID- 25756660
TI  - WITHDRAWN: Radical radiotherapy for stage I/II non-small cell lung cancer in
      patients not sufficiently fit for or declining surgery (medically inoperable).

PMID- 25756661
TI  - Toluene dioxygenase-catalyzed synthesis and reactions of cis-diol metabolites
      derived from 2- and 3-methoxyphenols.
AB  - Using toluene dioxygenase as biocatalyst, enantiopure cis-dihydrodiol and cis
      tetrahydrodiol metabolites, isolated as their ketone tautomers, were obtained
      from meta and ortho methoxyphenols. Although these isomeric phenol substrates are
      structurally similar, the major bioproducts from each of these biotransformations
      were found at different oxidation levels. The relatively stable cyclohexenone cis
      diol metabolite from meta methoxyphenol was isolated, while the corresponding
      metabolite from ortho methoxyphenol was rapidly bioreduced to a cyclohexanone cis
      diol. The chemistry of the 3-methoxycyclohexenone cis-diol product was
      investigated and elimination, aromatization, hydrogenation, regioselective O
      exchange, Stork-Danheiser transposition and O-methylation reactions were
      observed. An offshoot of this technology provided a two-step chemoenzymatic
      synthesis, from meta methoxyphenol, of a recently reported chiral fungal
      metabolite; this synthesis also established the previously unassigned absolute
      configuration. 

PMID- 25756662
TI  - CXC chemokines function as a rheostat for hepatocyte proliferation and liver
      regeneration.
AB  - BACKGROUND: Our previous in vitro studies have demonstrated dose-dependent
      effects of CXCR2 ligands on hepatocyte cell death and proliferation. In the
      current study, we sought to determine if CXCR2 ligand concentration is
      responsible for the divergent effects of these mediators on liver regeneration
      after ischemia/reperfusion injury and partial hepatectomy. METHODS: Murine models
      of partial ischemia/reperfusion injury and hepatectomy were used to study the
      effect of CXCR2 ligands on liver regeneration. RESULTS: We found that hepatic
      expression of the CXCR2 ligands, macrophage inflammatory protein-2 (MIP-2) and
      keratinocyte-derived chemokine (KC), was significantly increased after both I/R
      injury and partial hepatectomy. However, expression of these ligands after I/R
      injury was 30-100-fold greater than after hepatectomy. Interestingly, the same
      pattern of expression was found in ischemic versus non-ischemic liver lobes
      following I/R injury with expression significantly greater in the ischemic liver
      lobes. In both systems, lower ligand expression was associated with increased
      hepatocyte proliferation and liver regeneration in a CXCR2-dependent fashion. To
      confirm that these effects were related to ligand concentration, we administered
      exogenous MIP-2 and KC to mice undergoing partial hepatectomy. Mice received a
      "high" dose that replicated serum levels found after I/R injury and a "low" dose
      that was similar to that found after hepatectomy. Mice receiving the "high" dose
      had reduced levels of hepatocyte proliferation and regeneration whereas the "low"
      dose promoted hepatocyte proliferation and regeneration. CONCLUSIONS: Together,
      these data demonstrate that concentrations of CXC chemokines regulate the hepatic
      proliferative response and subsequent liver regeneration.

PMID- 25756663
TI  - A new, rapid, stability-indicating UPLC method for separation and determination
      of impurities in amlodipine besylate, valsartan and hydrochlorothiazide in their
      combined tablet dosage form.
AB  - A new rapid stability-indicating UPLC method for separation and determination of
      impurities in amlodipine besylate, valsartan and hydrochlorothiazide in their
      combined tablet dosage form was developed. The separation of Ph. Eur. related
      substances of amlodipine besylate (A, B, D, E, F, G), hydrochlorothiazide (A, B,
      C), valsartan (B, C), two other valsartan impurities (S)-2-(N-{[2'-cyanobiphenyl
      4-yl]methyl}pentanamido)-3-methylbutanoic acid and (S)-3-methyl-2-{[2'-(1H
      tetrazol-5-yl)biphenyl-4-yl]methylamino}butanoic acid and several unknown
      impurities was achieved by reversed phase liquid chromatography with UV
      detection. The detection wavelengths were set as follows: 225nm for valsartan,
      its impurities and for the impurity D of amlodipine, 271nm for
      hydrochlorothiazide and its impurities and 360nm for amlodipine and its
      impurities except for impurity D. Zorbax Eclipse C8 RRHD (100mm*3.0mm, 1.8MUm)
      was used as a separation column and the analytes were eluted within 11min by a
      programmed gradient mixture of 0.01M phosphate buffer pH 2.5 and acetonitrile.
      The method was successfully validated in accordance to the International
      Conference of Harmonization (ICH) guidelines for amlodipine besylate and its
      impurity D, valsartan and its impurity C and hydrochlorothiazide and its
      impurities A, B and C. The triple-combined tablets were exposed to thermal,
      higher humidity, acid, alkaline, oxidative and photolytic stress conditions.
      Stressed samples were analyzed by the proposed method. All the significant
      degradation products and impurities were satisfactory separated from each other
      and from the principal peaks of drug substances. The peak purity test complied
      for peaks of amlodipine, valsartan and hydrochlorothiazide in all the stressed
      samples and indicated no co-elution of degradation products. The method was found
      to be precise, linear, accurate, sensitive, specific, robust and stability
      indicating and could be used as a routine purity test method for amlodipine
      besylate, valsartan, hydrochlorothiazide and their pharmaceutical combinations.

PMID- 25756664
TI  - Safety and biodistribution of 111In-amatuximab in patients with mesothelin
      expressing cancers using single photon emission computed tomography-computed
      tomography (SPECT-CT) imaging.
AB  - Amatuximab is a chimeric high-affinity monoclonal IgG1/k antibody targeting
      mesothelin that is being developed for treatment of mesothelin-expressing
      cancers. Considering the ongoing clinical development of amatuximab in these
      cancers, our objective was to characterize the biodistribution, and dosimetry of
      111Indium (111In) radiolabelled amatuximab in mesothelin-expressing cancers.
      Between October 2011 and February 2013, six patients including four with
      malignant mesothelioma and two with pancreatic adenocarcinoma underwent Single
      Photon Emission Computed Tomography-Computed Tomography (SPECT/CT) imaging
      following administration of 111In amatuximab. SPECT/CT images were obtained at 2
      4 hours, 24-48 hours and 96-168 hours after radiotracer injection. In all
      patients, tumor to background ratios (TBR) consistently met or exceeded an uptake
      of 1.2 (range 1.2-62.0) which is considered the minimum TBR that can be
      visualized. TBRs were higher in tumors of patients with mesothelioma than
      pancreatic adenocarcinoma. 111In-amatuximab uptake was noted in both primary
      tumors and metastatic sites. The radiotracer dose was generally well-tolerated
      and demonstrated physiologic uptake in the heart, liver, kidneys and spleen. This
      is the first study to show tumor localization of an anti-mesothelin antibody in
      humans. Our results show that 111In-amatuximab was well tolerated with a
      favorable dosimetry profile. It localizes to mesothelin expressing cancers with a
      higher uptake in mesothelioma than pancreatic cancer. 

PMID- 25756666
TI  - Machine learning in the rational design of antimicrobial peptides.
AB  - One of the most important public health issues is the microbial and bacterial
      resistance to conventional antibiotics by pathogen microorganisms. In recent
      years, many researches have been focused on the development of new antibiotics.
      Among these, antimicrobial peptides (AMPs) have raised as a promising alternative
      to combat antibioticresistant microorganisms. For this reason, many theoretical
      efforts have been done in the development of new computational tools for the
      rational design of both better and effective AMPs. In this review, we present an
      overview of the rational design of AMPs using machine learning techniques and new
      research fields. 

PMID- 25756667
TI  - Ibalizumab-human CD4 receptor interaction: computational alanine scanning
      molecular dynamics studies.
AB  - Antibody drugs are used in the treatment of many chronic diseases. Recently,
      however, patients and doctors have encountered problems with drug resistance, and
      improving the affinity of antibody drugs has therefore become a pressing issue.
      Ibalizumab is a humanized monoclonal antibody that binds human CD4, the primary
      receptor for human immunodeficiency virus type 1 (HIV-1). In this study, we
      sought to identify the key residues of the complementaritydetermining regions
      (CDRs) of ibalizumab. Virtual alanine mutations (complementarity-determining
      regions of ibalizumab) were also studied using solvated interaction energies
      derived from molecular dynamics and the explicit water model. Using 1,000
      nanosecond molecular dynamic simulations, we identified six residues: Tyr50
      [HCDR2], Tyr53 [HCDR3], Asp58 [HCDR2], Glu95 [HCDR2], and Arg95 [LCDR3]. The
      Robetta alanine-scanning mutagenesis method and crystallographic information were
      used to verify our simulations. Our simulated binding affinity of -17.33 kcal/mol
      is close to the experimentally determined value of -16.48 kcal/mol. Our findings
      may be useful for protein engineering the structure of the ibalizumab-human CD4
      receptor complex. Moreover, the six residues that we identified may play a
      significant role in the development of bioactive antibody analogues. 

PMID- 25756668
TI  - Structural characterization of Bacillus subtilis membrane protein Bmr: an in
      silico approach.
AB  - Efflux pump--a membrane protein belonging to Major Facilitator (MF) family and
      associated with Multi Drug Resistance (MDR) has been a major factor in drug
      resistance of bacteria. In the era when no new effective antibiotic had been
      reported for years, the detailed study of these membrane proteins became
      imperative in order to improve the efficacy of existing drugs. The Bacillus
      subtilis membrane protein Bmr belongs to the super family of major facilitator
      proteins and is one of the first-discovered bacterial multidrug-efflux
      transporters. Development of Bmr inhibitors (B. subtilis) for least resistance,
      better drug sustainability and effective cellular activity requires three
      dimensional structure of this protein which has not yet been determined. In this
      communication structural characterization of this important efflux pump has been
      attempted using in silico approaches. The modeled structure of Bmr has been found
      to have 12 main helical segments interspersed by loops of variable lengths at
      regular intervals with both N- and C-termini on the same side of membrane.
      Docking of the known inhibitor reserpine on to the predicted structure of Bmr and
      its mutants signified the importance of the residues Phe143, Val286 and Phe306 in
      the interaction with the ligand. Besides this, the role of Arg313 and Phe309 in
      the H-bond formation and pi-pi interaction respectively, with reserpine was the
      new significant finding based on the interaction studies. The structure
      elucidation of Bmr and the role of these residues in binding to the ligand are
      expected to have a great impact on the efflux pump inhibition studies around the
      world and hence in the efficiency of the existing antibiotic drugs.

PMID- 25756665
TI  - Dexamethasone and azathioprine promote cytoskeletal changes and affect
      mesenchymal stem cell migratory behavior.
AB  - Glucocorticoids and immunosuppressive drugs are commonly used to treat
      inflammatory disorders, such as inflammatory bowel disease (IBD), and despite a
      few improvements, the remission of IBD is still difficult to maintain. Due to
      their immunomodulatory properties, mesenchymal stem cells (MSCs) have emerged as
      regulators of the immune response, and their viability and activation of their
      migratory properties are essential for successful cell therapy. However, little
      is known about the effects of immunosuppressant drugs used in IBD treatment on
      MSC behavior. The aim of this study was to evaluate MSC viability, nuclear
      morphometry, cell polarity, F-actin and focal adhesion kinase (FAK) distribution,
      and cell migratory properties in the presence of the immunosuppressive drugs
      azathioprine (AZA) and dexamethasone (DEX). After an initial characterization,
      MSCs were treated with DEX (10 MUM) or AZA (1 MUM) for 24 hrs or 7 days. Neither
      drug had an effect on cell viability or nuclear morphometry. However, AZA
      treatment induced a more elongated cell shape, while DEX was associated with a
      more rounded cell shape (P < 0.05) with a higher presence of ventral actin stress
      fibers (P < 0.05) and a decrease in protrusion stability. After 7 days of
      treatment, AZA improved the cell spatial trajectory (ST) and increased the
      migration speed (24.35%, P < 0.05, n = 4), while DEX impaired ST and migration
      speed after 24 hrs and 7 days of treatment (-28.69% and -25.37%, respectively; P
      < 0.05, n = 4). In conclusion, our data suggest that these immunosuppressive
      drugs each affect MSC morphology and migratory capacity differently, possibly
      impacting the success of cell therapy. 

PMID- 25756670
TI  - Molecular factors influencing the affinity of flavonoid compounds on P
      glycoprotein efflux transporter.
AB  - The most common mechanism of the so-called multidrug resistance (MDR), is mainly
      associated with an over expression of P-glycoprotein (Pgp). It is an ATP
      dependent transport protein that limits the intracellular accumulation of a
      variety of structurally unrelated compounds within various organs and normal
      tissues such as kidney, small intestine and the blood brain barrier. Thus, the
      expression of Pgp has a major impact on the pharmacokinetic profile of many
      therapeutic agents and therefore, overcoming Pgp-mediated efflux constitutes an
      attractive means of potentially enhancing their therapeutic efficacy. The
      flavonoids comprise a large group of polyphenolic compounds that occur in plants
      and vegetables, and they have been shown to display a wide variety of biological
      activities. For example, anti-inflammatory, antioxidant, antiallergic,
      hepatoprotective, antithrombotic, antiviral, and anticarcinogenic activities. The
      interactions between flavonoids and Pgp have also been extensively studied and
      some quantitative structure-activity relationships (QSAR) have been reported. In
      the present work, we have employed 2D-QSAR analysis to evaluate the interactions
      between Pgp and several flavonoid compounds with the aim of identifying the
      molecular factors responsible for the Pgp-binding affinity evidenced by these
      compounds. Thus, the reported data for dissociation constants (KD) between Pgp
      and 62 flavonoid compounds were modeled by means of multiple regression analysis
      (MLR), and structures of the compounds under study were characterized by means of
      calculated physicochemical properties and several topological and constitutional
      descriptors, as well as geometrical and quantum chemical indexes. The obtained
      results suggest that the hydrophobic and especially geometric factors are of
      prime importance for binding, whereas in the case of flavonoid derivatives with
      flavone (flavonols), flavanone and isoflavone nuclei, the electronic factors are
      also involved in electron donor/acceptor interactions. In addition, in the case
      of chalcones, the results suggest that the affinity toward P-gp of such compounds
      is mainly governed by intermolecular dispersive interactions at the binding site.

PMID- 25756669
TI  - More effective DPP4 inhibitors as antidiabetics based on sitagliptin applied QSAR
      and clinical methods.
AB  - Xanthine-based molecules such as serine protease dipeptidyl peptidase 4 (DPP4)
      inhibitors are compounds often used in improving glycemic control in type 2
      diabetic patients and also used for their effects as mild stimulants and as
      bronchodilators, notably in treating asthma symptoms. Here, we aim to better
      understand the molecular features affecting activity of xanthine-based DPP4
      inhibitors such as sitagliptin and related compounds and use these features to de
      novo predict improved sitagliptin derivatives. To this end, we performed a
      clinical study to examine the efficacy and safety of once-daily 100 mg oral
      sitagliptin as monotherapy in Romanian patients with type 2 diabetes. This study
      indicates that sitagliptin effectively decreases the glycemic level and provides
      very good glycemic equilibrium. To predict putative new drugs with identical
      pharmacological effects at lower dosages, we generate QSAR models based on
      compound series containing 35 DPP4 inhibitors. We establish that the
      physicochemical parameters critical for DPP4 inhibitory activity are:
      hydrophobicity described by the logarithm of the octanol/water partition
      coefficient, counts of rotatable bonds, hydrogen bond donor and acceptor atoms,
      and topological polar surface area. The predictive power of our QSAR models is
      indicated by significant values of statistical coefficients: cross-validated
      correlation q2 (0.77), fitted correlation coefficient r2 (0.85) and standard
      error of prediction (0.34). Based on the established QSAR equations, we propose
      and analyse 19 new sitagliptin derivatives with possibly improved pharmacological
      effect as DPP4 inhibitors. 

PMID- 25756671
TI  - Prediction of thrombin and factor xa inhibitory activity with associative neural
      networks.
AB  - Quantitative structure-activity relationship studies on a series of selective
      inhibitors of thrombin and factor Xa were performed by using Associative Neural
      Network. To overcome the problem of overfitting due to descriptor selection, 5
      fold cross-validation with variable selection in each step of the analysis was
      performed. The predictive ability of the models was tested through leave-one-out
      cross-validation, giving a Q2=0.74-0.87 for regression models. Predictions for
      the external evaluation sets obtained accuracies in the range of 0.71-0.82 for
      regressions. The proposed models can be potential tools for finding new drug
      candidates.

PMID- 25756672
TI  - QSAR models for the reactivation of sarin inhibited acetylcholinesterase by
      quaternary pyridinium oximes based on Monte Carlo method.
AB  - Monte Carlo method has been used as a computational tool for building QSAR models
      for the reactivation of sarin inhibited acetylcholinesterase (AChE) by quaternary
      pyridinium oximes. Simplified molecular input line entry system (SMILES) together
      with hydrogen-suppressed graph (HSG) was used to represent molecular structure.
      Total number of considered oximes was 46 and activity was defined as logarithm of
      the AChE reactivation percentage by oximes with concentration of 0.001 M. One
      variable models have been calculated with CORAL software for one data split into
      training, calibration and test set. Computational experiments indicated that this
      approach can satisfactorily predict the desired endpoint. Best QSAR model had the
      following statistical parameters: for training set r2=0.7096, s=0.177, MAE=0.148;
      calibration set: r2=0.6759, s=0.330, MAE=0.271 and test set: r2=0.8620, s=0.182,
      MAE=0.150. Structural indicators (SMILES based molecular fragments) for the
      increase and the decrease of the stated activity are defined. Using defined
      structural alerts computer aided design of new oxime derivatives with desired
      activity is presented.

PMID- 25756674
TI  - Does introduced fauna influence soil erosion? A field and modelling assessment.
AB  - Pigs (Sus scrofa) are recognised as having significant ecological impacts in many
      areas of the world including northern Australia. The full consequences of the
      introduction of pigs are difficult to quantify as the impacts may only be
      detected over the long-term and there is a lack of quantitative information on
      the impacts of feral pigs globally. In this study the effect of feral pigs is
      quantified in an undisturbed catchment in the monsoonal tropics of northern
      Australia. Over a three-year period, field data showed that the areal extent of
      pig disturbance ranged from 0.3-3.3% of the survey area. The mass of material
      exhumed through these activities ranged from 4.3 t ha(-1) yr(-1) to 36.0 t ha(-1)
      yr(-1). The findings demonstrate that large introduced species such as feral pigs
      are disturbing large areas as well as exhuming considerable volumes of soil. A
      numerical landscape evolution and soil erosion model was used to assess the
      effect of this disturbance on catchment scale erosion rates. The modelling
      demonstrated that simulated pig disturbance in previously undisturbed areas
      produced lower erosion rates compared to those areas which had not been impacted
      by pigs. This is attributed to the pig disturbance increasing surface roughness
      and trapping sediment. This suggests that in this specific environment,
      disturbance by pigs does not enhance erosion. However, this conclusion is
      prefaced by two important caveats. First, the long term impact of soil
      disturbance is still very uncertain. Secondly, modelling results show a clear
      differentiation between those from an undisturbed environment and those from a
      post-mining landscape, in which pig disturbance may enhance erosion.

PMID- 25756675
TI  - Characterization of typical aquatic humic substances in areas of sugarcane
      cultivation in Brazil using tetramethylammonium hydroxide thermochemolysis.
AB  - Aquatic humic substances (AHSs) differ from one environment to another depending
      on land use and occupation. In addition, the effects of planting sugarcane on
      AHSs are not well known. Thus, the aim of this study was to characterize AHSs
      extracted from a river in a typical region of sugarcane cultivation during dry
      and rainy seasons. The main characteristics of the AHSs were obtained using
      Fourier transformation infrared (FTIR) spectroscopy, nuclear magnetic resonance
      (NMR) spectroscopy and off-line pyrolysis coupled with gas chromatography and
      mass spectrometry (off-line tetramethylammonium hydroxide (TMAH)-GC-MS
      thermochemolysis). The FTIR and NMR results were used to infer that no
      distinctions occurred between the sampling periods. The samples were composed of
      aromatic groups that were potentially associated with the presence of residual
      vegetable materials (lignin). The results of the off-line TMAH-GC-MS
      thermochemolysis indicated that the structures of the AHSs had uniform
      compositions that were rich in fatty acid methyl esters (FAMEs), polysaccharide
      derivatives, aliphatic biopolymers derived from plants, long hydrocarbon chains,
      branched alkyl groups and methylene carbons. Thus, the results showed that the
      AHSs obtained from the sugarcane cultivation area during the crop period mainly
      consisted of resistant aliphatic hydrocarbons, which are derivatives of lignin
      and FAMEs in compounds rich in humic acid. Therefore, we concluded that sugarcane
      cultivation produces changes in AHSs because greater amounts of lignin
      derivatives were observed during the dry season, corresponding to sugarcane
      cultivation. 

PMID- 25756676
TI  - Effects of straw incorporation along with microbial inoculant on methane and
      nitrous oxide emissions from rice fields.
AB  - Incorporation of straw together with microbial inoculant (a microorganism agent,
      accelerating straw decomposition) is being increasingly adopted in rice
      cultivation, thus its effect on greenhouse gas (GHG) emissions merits serious
      attention. A 3-year field experiment was conducted from 2010 to 2012 to
      investigate combined effect of straw and microbial inoculant on methane (CH4) and
      nitrous oxide (N2O) emissions, global warming potential (GWP) and greenhouse gas
      intensity (GHGI) in a rice field in Jurong, Jiangsu Province, China. The
      experiment was designed to have treatment NPK (N, P and K fertilizers only),
      treatment NPKS (NPK plus wheat straw), treatment NPKSR (NPKS plus Ruilaite
      microbial inoculant) and treatment NPKSJ (NPKS plus Jinkuizi microbial
      inoculant). Results show that compared to NPK, NPKS increased seasonal CH4
      emission by 280-1370%, while decreasing N2O emission by 7-13%. When compared with
      NPKS, NPKSR and NPKSJ increased seasonal CH4 emission by 7-13% and 6-12%,
      respectively, whereas reduced N2O emission by 10-27% and 9-24%, respectively. The
      higher CH4 emission could be attributed to the higher soil CH4 production
      potential triggered by the combined application of straw and microbial inoculant,
      and the lower N2O emission to the decreased inorganic N content. As a whole, the
      benefit of lower N2O emission was completely offset by increased CH4 emission,
      resulting in a higher GWP for NPKSR (5-12%) and NPKSJ (5-11%) relative to NPKS.
      Due to NPKSR and NPKSJ increased rice grain yield by 3-6% and 2-4% compared to
      NPKS, the GHGI values for NPKS, NPKSR and NPKSJ were comparable. These findings
      suggest that incorporating straw together with microbial inoculant would not
      influence the radiative forcing of rice production in the terms of per unit of
      rice grain yield relative to the incorporation of straw alone.

PMID- 25756677
TI  - In situ tryptophan-like fluorometers: assessing turbidity and temperature effects
      for freshwater applications.
AB  - Tryptophan-like fluorescence (TLF) is an indicator of human influence on water
      quality as TLF peaks are associated with the input of labile organic carbon (e.g.
      sewage or farm waste) and its microbial breakdown. Hence, real-time measurement
      of TLF could be particularly useful for monitoring water quality at a higher
      temporal resolution than available hitherto. However, current understanding of
      TLF quenching/interference is limited for field deployable sensors. We present
      results from a rigorous test of two commercially available submersible tryptophan
      fluorometers (ex ~ 285, em ~ 350). Temperature quenching and turbidity
      interference were quantified in the laboratory and compensation algorithms
      developed. Field trials were then undertaken involving: (i) an extended
      deployment (28 days) in a small urban stream; and, (ii) depth profiling of an
      urban multi-level borehole. TLF was inversely related to water temperature
      (regression slope range: -1.57 to -2.50). Sediment particle size was identified
      as an important control on the turbidity specific TLF response, with signal
      amplification apparent <150 NTU for clay particles and <650 NTU for silt
      particles. Signal attenuation was only observed >200 NTU for clay particles.
      Compensation algorithms significantly improved agreement between in situ and
      laboratory readings for baseflow and storm conditions in the stream. For the
      groundwater trial, there was an excellent agreement between laboratory and raw in
      situ TLF; temperature compensation provided only a marginal improvement, and
      turbidity corrections were unnecessary. These findings highlight the potential
      utility of real time TLF monitoring for a range of environmental applications
      (e.g. tracing polluting sources and monitoring groundwater contamination).
      However, in situations where high/variable suspended sediment loads or rapid
      changes in temperature are anticipated concurrent monitoring of turbidity and
      temperature is required and site specific calibration is recommended for long
      term, surface water monitoring. 

PMID- 25756678
TI  - Higher diversity and abundance of denitrifying microorganisms in environments
      than considered previously.
AB  - Denitrification is an important process in the global nitrogen cycle. The genes
      encoding NirK and NirS (nirK and nirS), which catalyze the reduction of nitrite
      to nitric oxide, have been used as marker genes to study the ecological behavior
      of denitrifiers in environments. However, conventional polymerase chain reaction
      (PCR) primers can only detect a limited range of the phylogenetically diverse
      nirK and nirS. Thus, we developed new PCR primers covering the diverse nirK and
      nirS. Clone library and qPCR analysis using the primers showed that nirK and nirS
      in terrestrial environments are more phylogenetically diverse and 2-6 times more
      abundant than those revealed with the conventional primers. RNA- and culture
      based analyses using a cropland soil also suggested that microorganisms with
      previously unconsidered nirK or nirS are responsible for denitrification in the
      soil. PCR techniques still have a greater capacity for the deep analysis of
      target genes than PCR-independent methods including metagenome analysis, although
      efforts are needed to minimize the PCR biases. The methodology and the insights
      obtained here should allow us to achieve a more precise understanding of the
      ecological behavior of denitrifiers and facilitate more precise estimate of
      denitrification in environments.

PMID- 25756679
TI  - Clostridium difficile heterogeneously impacts intestinal community architecture
      but drives stable metabolome responses.
AB  - Clostridium difficile-associated diarrhoea (CDAD) is caused by C. difficile
      toxins A and B and represents a serious emerging health problem. Yet, its
      progression and functional consequences are unclear. We hypothesised that C.
      difficile can drive major measurable metabolic changes in the gut microbiota and
      that a relationship with the production or absence of toxins may be established.
      We tested this hypothesis by performing metabolic profiling on the gut microbiota
      of patients with C. difficile that produced (n=6) or did not produce (n=4) toxins
      and on non-colonised control patients (n=6), all of whom were experiencing
      diarrhoea. We report a statistically significant separation (P-value <0.05) among
      the three groups, regardless of patient characteristics, duration of the disease,
      antibiotic therapy and medical history. This classification is associated with
      differences in the production of distinct molecules with presumptive global
      importance in the gut environment, disease progression and inflammation.
      Moreover, although severe impaired metabolite production and biological deficits
      were associated with the carriage of C. difficile that did not produce toxins,
      only previously unrecognised selective features, namely, choline- and
      acetylputrescine-deficient gut environments, characterised the carriage of toxin
      producing C. difficile. Additional results showed that the changes induced by C.
      difficile become marked at the highest level of the functional hierarchy, namely
      the metabolic activity exemplified by the gut microbial metabolome regardless of
      heterogeneities that commonly appear below the functional level (gut bacterial
      composition). We discuss possible explanations for this effect and suggest that
      the changes imposed by CDAD are much more defined and predictable than previously
      thought. 

PMID- 25756680
TI  - Genomic and phenotypic differentiation among Methanosarcina mazei populations
      from Columbia River sediment.
AB  - Methanogenic archaea are genotypically and phenotypically diverse organisms that
      are integral to carbon cycling in anaerobic environments. Owing to their genetic
      tractability and ability to be readily cultivated, Methanosarcina spp. have
      become a powerful model system for understanding methanogen biology at the
      cellular systems level. However, relatively little is known of how genotypic and
      phenotypic variation is partitioned in Methanosarcina populations inhabiting
      natural environments and the possible ecological and evolutionary implications of
      such variation. Here, we have identified how genomic and phenotypic diversity is
      partitioned within and between Methanosarcina mazei populations obtained from two
      different sediment environments in the Columbia River Estuary (Oregon, USA).
      Population genomic analysis of 56 M. mazei isolates averaging <1% nucleotide
      divergence revealed two distinct clades, which we refer to as 'mazei-T' and
      'mazei-WC'. Genomic analyses showed that these clades differed in gene content
      and fixation of allelic variants, which point to potential differences in primary
      metabolism and also interactions with foreign genetic elements. This hypothesis
      of niche partitioning was supported by laboratory growth experiments that
      revealed significant differences in trimethylamine utilization. These findings
      improve our understanding of the ecologically relevant scales of genomic
      variation in natural systems and demonstrate interactions between genetic and
      ecological diversity in these easily cultivable and genetically tractable model
      methanogens. 

PMID- 25756681
TI  - Quantifying the relative roles of selective and neutral processes in defining
      eukaryotic microbial communities.
AB  - We have a limited understanding of the relative contributions of different
      processes that regulate microbial communities, which are crucial components of
      both natural and agricultural ecosystems. The contributions of selective and
      neutral processes in defining community composition are often confounded in field
      studies because as one moves through space, environments also change. Managed
      ecosystems provide an excellent opportunity to control for this and evaluate the
      relative strength of these processes by minimising differences between comparable
      niches separated at different geographic scales. We use next-generation
      sequencing to characterize the variance in fungal communities inhabiting adjacent
      fruit, soil and bark in comparable vineyards across 1000 kms in New Zealand. By
      compartmentalizing community variation, we reveal that niche explains at least
      four times more community variance than geographic location. We go beyond merely
      demonstrating that different communities are found in both different niches and
      locations by quantifying the forces that define these patterns. Overall,
      selection unsurprisingly predominantly shapes these microbial communities, but we
      show the balance of neutral processes also have a significant role in defining
      community assemblage in eukaryotic microbes.

PMID- 25756682
TI  - Incorporation of Time-of-Flight Information Reduces Metal Artifacts in
      Simultaneous Positron Emission Tomography/Magnetic Resonance Imaging: A
      Simulation Study.
AB  - OBJECTIVES: This study aimed to describe and evaluate the influence of time-of
      flight (TOF) information on metal artifact reduction in positron emission
      tomography (PET) image quality in clinical simultaneous PET/magnetic resonance
      (MR) scanning. MATERIALS AND METHODS: A total of 7 patients with various
      malignant tumors were included and underwent a PET/MR examination after standard
      PET/computed tomography. Baseline TOF and non-TOF PET images were reconstructed.
      Next, the TOF and non-TOF PET reconstructions were repeated after the
      introduction of artificial signal voids in the attenuation map to simulate metal
      artifacts of various sizes in a range of locations. Three different sizes of
      signal voids were inserted in the attenuation maps for each location of interest:
      over the maxilla, humeral head, chest, sternum, thoracic and lumbar spine, as
      well as the femoral head to replicate clinically relevant metal artifacts. The
      reconstructed images with the artifacts were then compared with the baseline
      reconstructed images. The mean percentage error in a region of interest
      surrounding the simulated artifact was used to compare between TOF and non-TOF
      images. Further comparison between TOF and non-TOF images was performed using
      histogram analysis. RESULTS: In all cases, the mean percentage error in a region
      of interest surrounding the simulated artifact was reduced when TOF information
      was included in the reconstruction. The inclusion of TOF also changes the
      distribution of smaller errors away from the origin of the artifact. In some
      anatomical regions, an increase in the number of small errors was noted with TOF,
      although the differences with non-TOF were minimal. CONCLUSIONS: Positron
      emission tomographic imaging benefits from the integration of TOF information in
      simultaneous PET/MR. The inclusion of TOF information in simultaneous PET/MR
      imaging reduces errors related to metal artifacts at the site of the artifact.

PMID- 25756683
TI  - Utility of Magnetic Resonance Imaging to Monitor Surgical Meshes: Correlating
      Imaging and Clinical Outcome of Patients Undergoing Inguinal Hernia Repair.
AB  - OBJECTIVES: From a surgeon's point of view, meshes implanted for inguinal hernia
      repair should overlap the defect by 3 cm or more during implantation to avoid
      hernia recurrence secondary to mesh shrinkage. The use of magnetic resonance
      imaging (MRI)-visible meshes now offers the opportunity to noninvasively monitor
      whether a hernia is still covered sufficiently in the living patient. The purpose
      of this study was therefore to evaluate the efficacy of hernia repair after mesh
      implantation based on MRI findings (mesh coverage, visibility of hernia
      structures) and based on the patient's postoperative symptoms. MATERIALS AND
      METHODS: In this prospective study approved by the ethics committee, 13 MRI
      visible meshes were implanted in 10 patients (3 bilaterally) for inguinal hernia
      repair between March 2012 and January 2013. Senior visceral surgeons (>7 years of
      experience) implanted the meshes via laparoscopic transabdominal preperitoneal
      procedure. Magnetic resonance imaging was performed within 1 week and at 3 months
      after surgery at a 1.5-T system. Mesh position, deformation, and coverage of the
      hernia were visually assessed in consensus and rated on a 4-point
      semiquantitative scoring system. Distances of hernia center point to the mesh
      borders (overlap) were measured. Mesh position and hernia coverage
      postoperatively and at 3 months after implantation were correlated with the
      respective patients' clinical symptoms. Statistical analysis was performed using
      the Wilcoxon signed rank test. RESULTS: Two of the 13 meshes presented with an
      atypical mesh configuration along the course of psoas muscle with a short medial
      overlap of less than 2 cm. Eleven of the 13 meshes exhibited a typical mesh
      configuration with lateral folding and initial overlap of more than 2 cm. Between
      baseline and 3 months' follow-up, average overlap decreased in the medial
      direction by -10% (3.75 cm vs 3.36 cm, P = 0.22), in the lateral direction by 
      20% (3.55 cm vs 2.82 cm, P = 0.01), in the superior direction by -2% (5.82 cm vs
      5.72 cm, P = 0.55), and in the posterior direction by -19% (4.11 cm vs 3.34 cm, P
      = 0.01). Between baseline and 3 months' follow-up, mesh folding increased mildly
      in the medial direction, whereas no change was found in the other directions.
      Individual folds of the mesh were flexible over time, whereas the gross visual
      configuration and location of meshes did not change. Four of the 13 former hernia
      sites were mildly painful at follow-up, whereas 9 of the 13 were completely
      asymptomatic. No correlation between clinical symptoms and mesh position or
      hernia coverage was found. CONCLUSIONS: Our results suggest that the actual
      postoperative mesh position after release of laparoscopic pneumoperitoneum may
      deviate from its position during surgery. Gross mesh position and configuration
      differed between patients but did not change within a given patient over the
      observation period of 3 months after surgery. We did not find a correlation
      between clinical symptoms and mesh configuration or position. Shrinkage of meshes
      does occur, yet not as concentric process, but regionally variable, leading to a
      reduced hernia coverage of up to -20% in the lateral and posterior directions.

PMID- 25756685
TI  - Gadodiamide and Dentate Nucleus T1 Hyperintensity in Patients With Meningioma
      Evaluated by Multiple Follow-Up Contrast-Enhanced Magnetic Resonance Examinations
      With No Systemic Interval Therapy.
AB  - The dentate nucleus of the cerebellum may appear as hyperintense on unenhanced T1
      magnetic resonance images (MRIs) of the brain. Recently, T1 signal hyperintensity
      has received attention owing to data on the association of this finding with the
      history of multiple injections of gadolinium-based contrast agents, specifically
      gadodiamide, in patients with multiple sclerosis and brain metastases. We
      conducted a retrospective study on patients with a meningioma who had routinely
      undergone follow-up enhanced MRI scans with gadodiamide. Across a time interval
      of 18 months (from January 2013 to July 2014), we identified 102 consecutive
      patients eligible for this study. A significant increase in T1 hyperintensity of
      the dentate nuclei of the cerebellum on nonenhanced scans was observed between
      the first and the last MRI in the group of patients with a history of at least 6
      enhanced MRI scans (P < 0.01), whereas no differences were observed in the group
      with 1 to 5 enhanced MRI scans (P = 0.74). Further research is necessary to shed
      light on the mechanism of the T1 hyperintensity as well as on the histological
      and microstructural appearance of the dentate nucleus after multiple intravenous
      injections of gadodiamide. The finding raises the question of substantial
      dechelation of this agent in patients with normal renal function.

PMID- 25756684
TI  - Nephrogenic systemic fibrosis risk after liver magnetic resonance imaging with
      gadoxetate disodium in patients with moderate to severe renal impairment: results
      of a prospective, open-label, multicenter study.
AB  - OBJECTIVE: The objective of this study was to assess the risk of gadoxetate
      disodium in liver imaging for the development of nephrogenic systemic fibrosis
      (NSF) in patients with moderate to severe renal impairment. MATERIALS AND
      METHODS: We performed a prospective, multicenter, nonrandomized, open-label phase
      4 study in 35 centers from May 2009 to July 2013. The study population consisted
      of patients with moderate to severe renal impairment scheduled for liver imaging
      with gadoxetate disodium. All patients received a single intravenous bolus
      injection of 0.025-mmol/kg body weight of liver-specific gadoxetate disodium. The
      primary target variable was the number of patients who develop NSF within a 2
      year follow-up period. RESULTS: A total of 357 patients were included, with 85
      patients with severe and 193 patients with moderate renal impairment, which were
      the clinically most relevant groups. The mean time period from diagnosis of renal
      disease to liver magnetic resonance imaging (MRI) was 1.53 and 5.46 years in the
      moderate and severe renal impairment cohort, respectively. Overall, 101 patients
      (28%) underwent additional contrast-enhanced MRI with other gadolinium-based MRI
      contrast agents within 12 months before the start of the study or in the follow
      up. No patient developed symptoms conclusive of NSF within the 2-year follow-up.
      CONCLUSIONS: Gadoxetate disodium in patients with moderate to severe renal
      impairment did not raise any clinically significant safety concern. No NSF cases
      were observed.

PMID- 25756686
TI  - Energy transfer based emission analysis of (Tb3+, Sm3+): lithium zinc phosphate
      glasses.
AB  - The present paper reports on the results pertaining to photoluminescence
      properties of Tb(3+), Sm(3+) and energy transfer from Tb(3+) to Sm(3+) ions in
      lithium zinc phosphate (LZP) glass matrix prepared by melt quenching method.
      Besides photoluminescence studies thermal stability for the LZP glass is also
      evaluated from TG-DTA measurement. Tb(3+) doped glasses have exhibited a
      prominent green emission at 547 nm assigned to (5)D4->(7)F5 transitions on
      exciting at lambda(exci)=377 nm. The quenching phenomenon in Tb(3+) emission on
      varying its concentration has been discussed from cross-relaxations. Sm(3+)
      incorporated glasses have shown strong orange emission at 603 nm assigned to
      (4)G5/2->(6)H7/2 transition upon exciting with lambda(exci)=404 nm. The
      possibility of energy transfer process taking place between these two ions is
      understood from the significant spectral overlap of Sm(3+) absorption and Tb(3+)
      emission. Migration of excitation energy from Tb(3+) ions to Sm(3+) ions at
      lambda(exci)=375 nm is evaluated from the emission spectra of (0.5 mol.%
      Tb(3+)+(0.5-2.0 mol.%) Sm(3+)) co-doped glasses. The emission intensity of Sm(3+)
      has enhanced while Tb(3+) emission intensity decreased with an increase in Sm(3+)
      concentration suggesting the occurrence of energy transfer through cross
      relaxations from Tb(3+) ((5)D4) to Sm(3+) ((4)G5/2). The mechanism behind energy
      transfer process has been further explained from energy level diagram, decay
      profiles and confirmed by calculating energy transfer parameters (energy transfer
      efficiency (eta) and energy transfer probability (P)) of co-doped glasses. The
      dipole-dipole interaction is found to be more responsible for energy transfer
      Tb(3+) ((5)D4) to Sm(3+) ((4)G5/2) ions in LZP glass matrix.

PMID- 25756687
TI  - Structural and spectroscopic characterizations of tetra-nuclear niobium(V)
      complexes of quinolinol derivatives.
AB  - Reactions between niobium ethoxide and 8-hydroxy-2-methylquinoline or 5-chloro-8
      hydroxyquinoline have been explored. Two new tetranuclear heteroleptic niobium
      complexes containing oxo, ethoxo, and quinolinate chelate rings have been
      synthesized and characterized by (1)H, (13)C and (93)Nb NMR, UV-Vis, and FT-IR
      spectroscopies, and single-crystal X-ray diffraction. The molecular structures of
      the niobium complexes, [Nb4(MU-O)4(MU-OEt)2(ONC10H8)2(OEt)8] (I) and [Nb4(MU
      O)4(MU-OEt)2(ONC9H5Cl)2(OEt)8] (II), are composed of a pair of edge-sharing
      bioctahedral moieties in which connected via two almost linear oxo-bridges, with
      a large difference in the NbO distances. Single-crystal structures showed both
      complexes are centrosymmetric and contain two distinct Nb centers, and results
      confirmed by observation of two niobium signals in the (93)Nb NMR spectra of
      complexes. 

PMID- 25756688
TI  - Crystal growth, structural characterization and theoretical investigation on 3,5
      dinitrosalicylic acid monohydrate for nonlinear optical applications.
AB  - Organic crystal of 3,5-dinitrosalicylic acid monohydrate has been grown by slow
      evaporation method at room temperature, using water as solvent. Quantum chemical
      calculations of energies, geometric structure and vibrational analysis of the
      title compound are carried out by DFT method with 6-31+G (d,p) basis set. Both
      the experimental and theoretical spectra confirm the presence of functional
      groups. Electric dipole moment, polarizability and the first order
      hyperpolarizability values have been computed theoretically. The (1)H and (13)C
      nuclear magnetic resonance (NMR) chemical shifts of the molecule are calculated
      by the gauge independent atomic orbital (GIAO) method and compared with the
      experimental results. The calculated HOMO-LUMO energies confirm the charge
      transfer within the molecule. Thermodynamic properties (heat capacity, entropy
      and enthalpy) of the title compound are determined. 

PMID- 25756689
TI  - Vibrational spectra (experimental and theoretical), molecular structure, natural
      bond orbital, HOMO-LUMO energy, Mulliken charge and thermodynamic analysis of N'
      hydroxy-pyrimidine-2-carboximidamide by DFT approach.
AB  - The FT-IR, FT-Raman, (1)H, (13)C NMR and UV-Visible spectral measurements of N'
      hydroxy-pyrimidine-2-carboximidamide (HPCI) and complete analysis of the observed
      spectra have been proposed. DFT calculation has been performed and the structural
      parameters of the compound was determined from the optimized geometry with 6
      311+G(d,p) basis set and giving energies, harmonic vibrational frequencies and
      force constants. The results of the optimized molecular structure are presented
      and compared with the experimental. The geometric parameters, harmonic
      vibrational frequencies and chemical shifts were compared with the experimental
      data of the molecule. The title compound, C5H6N4O, is approximately planar, with
      an angle of 11.04 (15) degrees . The crystal structure is also stabilized by
      intermolecular N-H?O, N-H?N, O-H?N, C-H?O hydrogen bond and offset pi-pi stacking
      interactions. The influences of hydroxy and carboximidamide groups on the
      skeletal modes and proton chemical shifts have been investigated. Moreover, we
      have not only simulated highest occupied molecular orbital (HOMO) and lowest
      unoccupied molecular orbital (LUMO) but also determined the transition state and
      band gap. The kinetic, thermodynamic stability and chemical hardness of the
      molecule have been determined. Complete NBO analysis was also carried out to find
      out the intermolecular electronic interactions and their stabilization energy.
      The thermodynamic properties like entropies and their correlations with
      temperatures were also obtained from the harmonic frequencies of the optimized
      structure. 

PMID- 25756690
TI  - Novel styrylbenzothiazolium dye-based sensor for mercury, cyanide and hydroxide
      ions.
AB  - We report the design and synthesis of a novel styrylbenzothiazolium (3)
      derivative developed as a fluorescent and colorimetric chemodosimeter with high
      selectivity toward Hg(2+), CN(-) and OH(-) ions. An obvious loss of pink color in
      the presence of Hg(2+) and CN(-) ions could make it a suitable "naked eye"
      indicator. We propose a sensing mechanism whereby the benzenoid form is changed
      to a quinoid form upon Hg(2+) binding in a 1:1 stoichiometric ratio. More
      significantly, the styrylbenzothiazolium-Hg(2+) and styrylbenzothiazolium-CN(-)
      complexes exhibited a dual-channel chromo-fluorogenic response. The sensors
      exhibit remarkable Hg(2+)-, CN(-)-, and OH(-)-selective red fluorescence but
      remain dark-green in the presence of a wide range of tested metal ions and
      anions. 

PMID- 25756691
TI  - Differential role of estrogen receptor modulators in depression-like behavior and
      memory impairment in rats with postmenopausal diabetes.
AB  - OBJECTIVE: Diabetes and menopause are frequent comorbidities. The objective of
      the present study was to delineate the effects of nonselective and selective
      estrogen receptor (ER) agonists (alpha and beta) on cognitive function and
      depressive behavior in ovariectomized diabetic (Ovx-Dia) rats. METHODS: Bilateral
      ovariectomy was performed in female Sprague-Dawley rats (200-250 g), and
      streptozotocin was used to induce experimental diabetes. Rats were administered
      (10 MUg/kg SC) a nonselective ER agonist, 17beta-estradiol (E2); a selective ER
      alpha agonist, propionitrile (PPT; 4,4',4"-(4-propyl-[1H] pyrazole-1,3,5-triyl)
      tris phenol); and a selective ER-beta agonist, 2,3-bis(4-hydroxyphenyl)
      propionitrile (DPN) for 4 weeks after streptozotocin injection. RESULTS: Marked
      impairment in memory indicated by increased transfer latency on the fifth day
      (363%) and increased immobility time (90.5%), coupled with a marked decrease in
      brain-derived neurotrophic factors (22.5%) and increase in acetylcholinesterase
      activity (58.1%), were observed in Ovx-Dia rats compared with sham rats. However,
      a partial change in all these parameters was observed in ovariectomized or
      diabetic rats compared with sham rats. Treatment with DPN and E2 markedly
      prevented--whereas treatment with PPT partially prevented--changes induced in Ovx
      Dia rats. To assess feminizing action, we measured serum estradiol levels and
      uterine weights. E2 reversed the ovariectomy-induced decrease in serum estradiol
      levels and uterine weights, but PPT and DPN treatment did not show any effect.
      CONCLUSIONS: Results reveal that specific ER-beta agonists can ameliorate memory
      dysfunction and depressive behavior associated with postmenopausal diabetes and
      are devoid of the feminizing adverse effects of nonselective ER agonists.

PMID- 25756692
TI  - Safety of 3-year raloxifene treatment in Japanese postmenopausal women aged 75
      years or older with osteoporosis: a postmarketing surveillance study.
AB  - OBJECTIVE: Long-term safety of medication is a concern for older persons because
      they may have several comorbidities that can influence drug metabolism, efficacy,
      and safety. In Japan, raloxifene is an effective and well-tolerated medication
      for the treatment of osteoporosis in postmenopausal women, but there is little
      available evidence on whether raloxifene has an acceptable safety profile in
      older women. The objective of this post hoc analysis was to investigate the
      safety of raloxifene as a long-term treatment of osteoporosis in Japanese
      postmenopausal women aged 75 years or older. METHODS: We report a post hoc
      analysis of a safety dataset (6,960 participants) from a published postmarketing
      surveillance study (postmenopausal women treated with raloxifene 60 mg/d for <=3
      y). The safety dataset was divided into two groups: (1) women younger than 75
      years at baseline (4,522 participants) and (2) women aged 75 years or older at
      baseline (2,438 participants). Incidence of adverse drug reactions and reactions
      of note in each age group were compared using Fisher's exact test. RESULTS:
      Approximately 10% of women in each group reported at least one adverse drug
      reaction. This analysis did not identify any clinically important differences in
      the incidence or type of adverse drug reactions reported or in reactions of note
      between women aged 75 years or older and younger women. CONCLUSIONS: There were
      no obvious additional safety concerns for women aged 75 years or older who were
      treated with raloxifene. The findings in this post hoc evaluation suggest no
      differences in adverse events in the age groups evaluated.

PMID- 25756693
TI  - Long-term follow-up of bone density in women with primary ovarian insufficiency.
AB  - OBJECTIVE: This study aims to analyze long-term variation in bone mineral density
      among young women with primary ovarian insufficiency. METHODS: A cohort study
      evaluated bone mineral density in 72 women with primary ovarian insufficiency who
      were receiving estrogen + progestogen therapy. Bone mineral density was evaluated
      every 2 years for 8 years. RESULTS: The women were young, with a mean (SD) age of
      34.1 (6.7) years and had a bone density measurement at baseline. The mean (SD)
      time between the last menstruation and the beginning of hormone treatment was 2.9
      (4.2) years. The initial mean (SD) bone mineral density was 1.03 (0.17) and 0.91
      (0.16) g/cm for the lumbar spine and femoral neck, respectively. The mean (SD) T
      score was -1.03 (1.39) and -0.29 (1.09) for the lumbar spine and femoral neck,
      respectively. Bone mineral density measurements after a follow-up period of 2, 4,
      6, and 8 years did not differ from bone mineral density at baseline. Osteopenia
      and osteoporosis were observed at the lumbar spine and femoral neck in 46% and
      25% of women at the time of diagnosis, with no difference in the percentage of
      affected women across time. CONCLUSIONS: Although women with primary ovarian
      insufficiency who are receiving estrogen + progestogen therapy maintain stable
      bone mass throughout an 8-year follow-up period, this treatment is not sufficient
      to decrease the number of women who experience some level of low bone density.
      Therapeutic regimens should be reviewed, probably with resumption of discussions
      about the need for other therapeutic strategies.

PMID- 25756694
TI  - Hormone therapy and risk of all-cause mortality in women treated with statins.

PMID- 25756695
TI  - Antidepressants decrease hot flashes and improve life quality.

PMID- 25756696
TI  - Short-term effects on voiding function after mesh-related surgical repair of
      advanced pelvic organ prolapse.
AB  - OBJECTIVE: This study aims to evaluate postoperative short-term voiding
      dysfunction and voiding function at 3 months after mesh-related advanced pelvic
      organ prolapse (POP) repair among Chinese women. METHODS: In this prospective
      cohort study, 171 women with advanced anterior POP underwent mesh-related
      surgical repair using the new economical surgical method at Peking Union Medical
      College Hospital. Postoperative voiding dysfunction (PVD) was defined as a
      postvoid residual volume (PVR) of 100 mL or more or greater than one third of the
      voided volume. Assessment of voiding function included preoperative and
      postoperative uroflowmetry, PVR examination, and the Chinese versions of the
      Urinary Distress Inventory-6 and the Incontinence Impact Questionnaire Short
      Form. T test, chi test, Fisher's exact test, and multivariate logistic regression
      were used for data analyses. RESULTS: Of the 171 women, 48 (28.1%) exhibited PVD,
      and 22 (12.9%) exhibited a residual urine volume of 200 mL or more. Twenty-eight
      (58.3%) of 48 women reported symptom resolution within 3 days. Women with a
      residual urine volume of 200 mL or more experienced greater difficulty recovering
      (P = 0.001). A higher Pelvic Organ Prolapse Quantification stage in the anterior
      compartment (odds ratio, 7.94; 95% CI, 2.1-30.3) and a lower preoperative average
      urine flow rate (odds ratio, 3.92; 95% CI, 1.90-8.06) were independent risk
      factors for PVD. The Urinary Distress Inventory-6 and the Incontinence Impact
      Questionnaire Short Form indicated significant improvement from baseline at 3
      months after surgical operation (P = 0.026 and P = 0.043, respectively), whereas
      average flow rate and bladder capacity significantly decreased from baseline (P =
      0.011 and P < 0.001, respectively). CONCLUSIONS: Women with a higher Pelvic Organ
      Prolapse Quantification stage in the anterior compartment and a lower
      preoperative average urine flow rate are prone to PVD, whereas a cutoff PVR value
      of 200 mL might be appropriate for defining PVD to avoid potential overtreatment.

PMID- 25756697
TI  - Incidence of endometrial spotting or bleeding during continuous-combined estrogen
      progestin therapy in postmenopausal women with and without hypertension.
AB  - OBJECTIVE: Endometrial spotting or bleeding is a common adverse effect among
      women taking continuous-combined estrogen-progestin therapy. The renin
      angiotensin-aldosterone system plays a major role in hypertension and is present
      in the endometrium. We hypothesized that postmenopausal women with hypertension
      would have a higher incidence of bleeding compared with postmenopausal women
      without hypertension. METHODS: A multivariate mixed-effects logistic model
      estimated the odds ratios for the relationship of hypertension status or use of
      antihypertensive drugs with endometrial bleeding using the Women's Health
      Initiative database. RESULTS: The incidence of spotting or bleeding in the first
      12 months of estrogen-progestin use was 42% in women aged 50 to 79 years. Women
      with hypertension were more likely to experience bleeding than women without
      hypertension (odds ratio, 1.07; 95% CI, 1.02-1.13). Overall antihypertensive
      medication use increased bleeding with an odds ratio of 1.24, whereas angiotensin
      II receptor antagonists had a reduced odds ratio (0.53). CONCLUSIONS:
      Postmenopausal women with hypertension are more likely to bleed than
      postmenopausal women without hypertension when taking continuous estrogen
      progestin, with less bleeding in women using angiotensin II receptor antagonists.
      This finding is novel and supports our hypothesis that the endometrial renin
      angiotensin-aldosterone system may contribute to endometrial bleeding.

PMID- 25756698
TI  - Prevalence and predictors of storage lower urinary tract symptoms in
      perimenopausal and postmenopausal women attending a menopause clinic.
AB  - OBJECTIVE: This study was undertaken to evaluate the prevalence and predictors of
      storage lower urinary tract symptoms (LUTS) in perimenopausal and postmenopausal
      women attending a menopause clinic. METHODS: The records of 351 women aged 40 to
      76 years who enrolled in a health and nutrition education program at a menopause
      clinic were analyzed cross-sectionally. The prevalence of frequency, nocturia,
      urge incontinence, and stress incontinence was estimated based on women's
      responses to the Menopausal Health-Related Quality of Life Questionnaire. Effects
      of background characteristics, including age, menopause status, vaginal dryness,
      body composition, cardiovascular parameters, physical fitness, and psychological
      symptoms, on storage LUTS were assessed using multivariate logistic regression
      analysis. RESULTS: Frequency, nocturia, urge incontinence, and stress
      incontinence were reported by 45.9%, 10.8%, 11.4%, and 32.8% of women,
      respectively. Multiple logistic regression analysis revealed independent
      associations between storage LUTS and the following predictors after adjustment:
      frequency was associated with nonrestorative sleep score (odds ratio, 1.63; 95%
      CI, 1.35-1.95); nocturia was associated with nonrestorative sleep score (odds
      ratio, 2.26; 95% CI, 1.57-3.25) and waist-to-hip ratio (odds ratio, 1.12; 95% CI,
      1.05-1.18); urge incontinence was associated with reaction time (odds ratio,
      1.10; 95% CI, 1.01-1.19); and stress incontinence was associated with body fat
      (odds ratio, 1.06; 95% CI, 1.03-1.09). CONCLUSIONS: Storage LUTS are highly
      prevalent in perimenopausal and postmenopausal women attending a menopause
      clinic. Nonrestorative sleep score is associated with frequency and nocturia;
      body fat and visceral fat accumulation are associated with nocturia and stress
      incontinence; and delayed reaction time is associated with urge incontinence.
      Careful evaluation of nonrestorative sleep, body fat and visceral fat
      accumulation, or delayed reaction time might reveal undisclosed storage LUTS in
      this population.

PMID- 25756699
TI  - Hot flashes across the life span: adjusting the lens.

PMID- 25756700
TI  - Relationship Between Training Intensity and Volume and Hypothyroidism Among
      Female Runners.
AB  - OBJECTIVE: To determine the effect of training intensity on thyroid function
      among female nonelite runners. DESIGN: Internet-based survey of medical history
      and training and racing habits of female runners. PARTICIPANTS: A total of 1222
      female runners aged >=35 years. MAIN OUTCOME MEASURES: Self-reported diagnosis of
      hypothyroidism and details of training and racing. RESULTS: Hypothyroidism was
      reported by 149 (12.2%). No characteristics of training intensity or duration,
      including average miles per week, training pace, or years of accumulated running
      were associated with thyroid dysfunction. Females who began running at or before
      age 10 were more likely to report a diagnosis of hypothyroidism versus those who
      began running at an older age (4.7% vs 1.5%, P = 0.018). CONCLUSIONS: Our results
      do not support the concept of overtraining-related hypothyroidism among nonelite
      female distance runners although our data demonstrated a 3-fold increase in
      hypothyroidism among those who began a career at or before age 10. Further study
      is required to confirm and determine a possible mechanism of this association.

PMID- 25756702
TI  - Synthesis, characterization and structure of nickel and copper compounds
      containing ligands derived from keto-enehydrazines and their catalytic
      application for aerobic oxidation of alcohols.
AB  - Ligand precursors HL(R,Ph) (R = Me, Ph) were synthesised by condensation of
      acetylacetone and the corresponding N,N-substituted hydrazines and were
      characterised spectroscopically and structurally. Both in the solid state and in
      solution they behave as (Z)-keto-enehydrazines and this was confirmed by DFT
      calculations which showed that this form was the most stable of their possible
      tautomers. The reaction of HL(R,Ph) compounds with copper acetate and nickel
      acetate in EtOH afforded the corresponding complexes [M(L(R,Ph))2] (M = Cu, Ni; R
      = Me, Ph). The methyl-substituted derivatives were structurally characterised by
      X-ray methods. A four-coordinate environment around the metal centre, where the
      two L(Me,Ph) ligands act as bidentate N,O-chelators and lie in a pseudo-trans
      conformation, was found for both compounds. The dihedral angle between the two
      six-membered metallacycles M(L(Me,Ph)) was 0 degrees  for nickel, a typical
      square planar coordination, meanwhile it was 23 degrees  for copper, a square
      planar slightly distorted to pseudotetrahedral coordination. Copper complexes
      [Cu(L(R,Ph))2] were tested as catalysts, in combination with TEMPO (2,2,6,6
      tetramethylpiperidine-N-oxyl radical), for the aerobic oxidation of 4-nitrobenzyl
      alcohol as the model reaction. An almost complete conversion to the corresponding
      aldehyde was observed after 1 h at 60  degrees C and 1 bar of dioxygen, in
      toluene as the solvent. Importantly, air at atmospheric pressure was also
      observed to be appropriate for the oxidation, although longer reaction times were
      required. After the optimization of the reaction conditions, the study was
      extended to other alcohol substrates and good catalytic activity was found for
      benzylic-type alcohols, while low yield was found for 1-octanol. 

PMID- 25756701
TI  - Cardiovascular and Musculoskeletal Assessment of Elite US Volleyball Players.
AB  - OBJECTIVE: The aim of this study was to characterize the cardiovascular and
      musculoskeletal systems of elite volleyball players, including aortic dimensions.
      Previous studies have shown that the upper limit of normal aortic sinus diameter
      for male and female athletes is 4 and 3.4 cm, respectively. DESIGN: Cross
      sectional analysis. SETTING: United States Olympic Volleyball Training Facility
      and Rady Children's Hospital San Diego. PARTICIPANTS: Seventy (37 male) members
      of the US national volleyball team. MAIN OUTCOME MEASURES: Athletes underwent
      evaluation that included medical and family histories, targeted physical
      examinations specifically focusing on abnormalities present in Marfan syndrome
      (MFS), and transthoracic echocardiograms. Cardiac chamber and great artery size,
      valve function, and coronary artery origins were assessed. RESULTS: Three male
      athletes (8%) had an aortic sinus diameter >=4 cm, one of whom also had an
      ascending aorta >4 cm. Two female athletes (6%) had aortic sinus diameter >=3.4
      cm, and another had an ascending aorta of 3.4 cm. There were no other
      intracardiac or arterial abnormalities. Individual musculoskeletal
      characteristics of MFS were common among the athletes but not more frequent or
      numerous in those with aortic dilation. CONCLUSIONS: The prevalence of aortic
      root dilation in this population of athletes was higher than what has previously
      been reported in other similar populations. Further study is needed to determine
      whether these represent pathological changes or normal variations in tall
      athletes. CLINICAL RELEVANCE: This study adds to the existing knowledge base of
      athlete's heart, with specific attention to aortic dimensions in elite volleyball
      players. The data are relevant to similar athletes' medical care and to
      preparticipation cardiac screening in general.

PMID- 25756703
TI  - Multifractality in heartbeat dynamics in patients undergoing beating-heart
      myocardial revascularization.
AB  - BACKGROUND: The multifractal approach of HRV analysis offers new insight into the
      mechanisms of autonomic modulation of the diseased hearts and has a potential to
      depict subtle changes in cardiac autonomic nervous control not revealed by
      conventional linear and non-linear analyses in various conditions like heart
      failure or stable angina pectoris. The aim of this study was to employ the
      multifractality approach in cardiac surgery patients and evaluate the
      multifractality before and after beating-heart myocardial revascularization (off
      pump CABG). METHODS: Twenty-four hour Holter recordings were performed pre- and
      postoperatively in 60 patients undergoing off-pump CABG. Selected conventional
      time- and frequency-domain linear HRV indices were calculated from the 24h and 5
      min ECG segments, and preselected multifractal parameters tau(q=2), tau(q=3),
      h_top and Deltah were determined for daytime (12:00-18:00) and nighttime (00:00
      06:00) periods of the ECG recordings using Ivanov's method. Mean differences over
      time were tested using paired-samples t-test and exact Wilcoxon matched-pairs
      test. The results are reported as mean +/- SD and median with interquartile
      range. A p value of <0.05 was considered statistically significant. RESULTS: All
      selected conventional linear HRV parameters decreased significantly after off
      pump CABG (p from <0.001-0.015). Preoperatively, multifractal parameter tau(q=2)
      was -0.60 +/- 0.12 and -0.54 +/- 0.12, tau(q=3) -0.52 +/- 0.18 and -0.49 +/-
      0.17, h_top 0.20 +/- 0.07 and 0.15 +/- 0.07 and Deltah 0.31 +/- 0.14 and 0.17 +/-
      0.14 for daytime and nighttime periods, respectively. Postoperatively, tau(q=2)
      and tau(q=3) were significantly higher for daytime (-0.49 +/- 0.15, p<0.001 and 
      0.43 +/- 0.23, p=0.015), whereas h_top and Deltah were significantly higher for
      both daytime and nighttime (0.25 +/- 0.07, p<0.001 and 0.19 +/- 0.06, p=0.002 for
      h_top and 0.41 +/- 0.20, p=0.003 and 0.31 +/- 0.19, p < 0.001 for Deltah,
      respectively). All pre- and postoperative parameters, except tau(q=2) and
      tau(q=3) preoperatively, were significantly lower for nighttime as compared to
      daytime periods. CONCLUSIONS: A significant breakdown of multifractal complexity
      and anti-correlation behavior with a significant sympathetic overdrive and a
      concomitant parasympathetic withdrawal occurs after off-pump CABG. The circadian
      pattern of multifractality regains its day-night variation in the first week
      after the surgical procedure.

PMID- 25756704
TI  - Computerized segmentation and measurement of chronic wound images.
AB  - An estimated 6.5 million patients in the United States are affected by chronic
      wounds, with more than US$25 billion and countless hours spent annually for all
      aspects of chronic wound care. There is a need for an intelligent software tool
      to analyze wound images, characterize wound tissue composition, measure wound
      size, and monitor changes in wound in between visits. Performed manually, this
      process is very time-consuming and subject to intra- and inter-reader
      variability. In this work, our objective is to develop methods to segment,
      measure and characterize clinically presented chronic wounds from photographic
      images. The first step of our method is to generate a Red-Yellow-Black-White
      (RYKW) probability map, which then guides the segmentation process using either
      optimal thresholding or region growing. The red, yellow and black probability
      maps are designed to handle the granulation, slough and eschar tissues,
      respectively; while the white probability map is to detect the white label card
      for measurement calibration purposes. The innovative aspects of this work include
      defining a four-dimensional probability map specific to wound characteristics, a
      computationally efficient method to segment wound images utilizing the
      probability map, and auto-calibration of wound measurements using the content of
      the image. These methods were applied to 80 wound images, captured in a clinical
      setting at the Ohio State University Comprehensive Wound Center, with the ground
      truth independently generated by the consensus of at least two clinicians. While
      the mean inter-reader agreement between the readers varied between 67.4% and
      84.3%, the computer achieved an average accuracy of 75.1%. 

PMID- 25756705
TI  - Region-based snake with edge constraint for segmentation of lymph nodes on CT
      images.
AB  - Lymph nodes segmentation is a tedious process with large inter-user variability
      when performed manually. To facilitate lymph nodes assessment for lung cancer
      patient, we present an automatic and improved snake segmentation method for
      thoracic lymph nodes on CT images in this paper. We first investigated the
      performance of both edge-based and region-based snake algorithms for the
      segmentation task, using a B-spline contour parameterization. The effect of the
      number of B-spline control points on the snake performance was also examined.
      Both edge-based and region-based snakes were found to have their own advantages
      and disadvantages for lymph nodes segmentation. We further developed a method of
      region-based snake with edge constraint, which utilizes a self-adjusting
      mechanism to integrate both edge and region information in a constructive manner.
      The average Dice Similarity Coefficient obtained was 0.853 +/- 0.059 and 0.841 +/
      0.108 for the baseline and follow-up lymph nodes respectively using the proposed
      method. The method was found to be an effective lymph node segmentation method
      and would potentially be useful to help with treatment response evaluations in
      the clinical practice.

PMID- 25756706
TI  - The DSM-5 alternative model of personality disorders from the perspective of
      adult attachment: a study in community-dwelling adults.
AB  - To assess how the maladaptive personality domains and facets that were included
      in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM
      5) Alternative Model of Personality Disorders relate to adult attachment styles,
      480 Italian nonclinical adults were administered the Personality Inventory for
      DSM-5 (PID-5) and the Attachment Style Questionnaire (ASQ). To evaluate the
      uniqueness of the associations between the PID-5 scales and the ASQ scales, the
      participants were also administered the Big Five Inventory (BFI). Multiple
      regression analyses showed that the ASQ scales significantly predicted both PID-5
      domain scales and BFI scales; however, the relationships were different both
      qualitatively and quantitatively. With the exception of the PID-5 risk taking
      scale (adjusted R(2) = 0.02), all other PID-5 trait scales were significantly
      predicted by the ASQ scales, median adjusted R(2) value = 0.25, all ps < 0.001.
      Our findings suggest that the maladaptive personality domains and traits listed
      in the DSM-5 Alternative Model of Personality Disorders show meaningful
      associations with adult attachment styles.

PMID- 25756707
TI  - An exploration of reported cognitions during an earthquake and its aftershocks:
      differences across affected communities and associations with psychological
      distress.
AB  - Cognitive themes in two communities differentially affected by the September 2010
      Christchurch earthquake and aftershocks were investigated. Participants (N = 124)
      completed questions about their thoughts during the earthquake and aftershocks as
      well as measures of acute stress, anxiety, and depression. Cognitions were
      qualitatively analyzed into themes for the earthquake and aftershocks. Themes
      were examined for differences across the two suburbs and associations with
      psychological distress. Nine cognitive themes were identified within three
      superordinate domains. The cognitive theme of worry and concern was the most
      frequently occurring for the earthquake and aftershocks across the whole sample
      and for the more affected suburb. Current threat was the most frequent theme for
      the earthquake in the less affected suburb, whereas worry and concern was the
      most evident in this group for aftershocks. The superordinate theme of threat was
      significantly related to higher acute stress disorder scores in the more affected
      suburb for earthquake-reported cognitions. 

PMID- 25756708
TI  - The complex role of personality in cancer treatment: impact of dependency
      detachment on health status, distress, and physician-patient relationship.
AB  - Personality traits have been associated with positive and negative adjustment to
      a cancer diagnosis. No studies have assessed trait dependency and detachment and
      their relationship to health, distress, and the doctor-patient relationship in
      patients undergoing radiation treatment for cancer. Fifty adults (32 women; mean
      [SD], 60.32 [12.74] years) undergoing radiation treatment for a variety of
      cancers completed measures of dependency and detachment, doctor-patient
      relationship, physical health, somatization, anxiety, and depression.
      Overdependence scores were positively and significantly correlated with patients'
      anxiety and negatively and significantly correlated with the physician-patient
      relationship. Detachment scores were positively and significantly correlated with
      pain, somatization, depression, and anxiety and marginally associated with lower
      health-related quality of life. These preliminary findings support the construct
      validity and clinical utility of trait dependency and detachment testing with
      oncology patients and suggest that detachment is associated with poorer quality
      of life and higher psychological distress, whereas dependency is associated with
      poorer doctor-patient relationships after a cancer diagnosis. 

PMID- 25756709
TI  - A look at the effect of sequence complexity on pressure destabilisation of DNA
      polymers.
AB  - Our previous studies on the helix-coil transition of double-stranded DNA polymers
      have demonstrated that molar volume change (DeltaV) accompanying the thermally
      induced transition can be positive or negative depending on the experimental
      conditions, that the pressure-induced transition is more cooperative than the
      heat-induced transition [Rayan and Macgregor, J Phys Chem B2005, 109, 15558
      15565], and that the pressure-induced transition does not occur in the absence of
      water [Rayan and Macgregor, Biophys Chem, 2009, 144, 62-66]. Additionally, we
      have shown that DeltaV values obtained by pressure-dependent techniques differ
      from those obtained by ambient pressure techniques such as PPC [Rayan et al. J
      Phys Chem B2009, 113, 1738-1742] thus shedding light on the effects of pressure
      on DNA polymers. Herein, we examine the effect of sequence complexity, and hence
      cooperativity on pressure destabilisation of DNA polymers. Working with
      Clostridium perfringes DNA under conditions such that the estimated DeltaV of the
      helix-coil transition corresponds to -1.78 mL/mol (base pair) at atmospheric
      pressure, we do not observe the pressure-induced helix-coil transition of this
      DNA polymer, whereas synthetic copolymers poly[d(A-T)] and poly[d(I-C)] undergo
      cooperative pressure-induced transitions at similar DeltaV values. We hypothesise
      that the reason for the lack of pressure-induced helix-coil transition of C.
      perfringens DNA under these experimental conditions lies in its sequence
      complexity.

PMID- 25756710
TI  - Can emergency physicians accurately and reliably assess acute vertigo in the
      emergency department?
AB  - OBJECTIVE: To validate a clinical diagnostic tool, used by emergency physicians
      (EPs), to diagnose the central cause of patients presenting with vertigo, and to
      determine interrater reliability of this tool. METHODS: A convenience sample of
      adult patients presenting to a single academic ED with isolated vertigo (i.e.
      vertigo without other neurological deficits) was prospectively evaluated with
      STANDING (SponTAneousNystagmus, Direction, head Impulse test, standiNG) by five
      trained EPs. The first step focused on the presence of spontaneous nystagmus, the
      second on the direction of nystagmus, the third on head impulse test and the
      fourth on gait. The local standard practice, senior audiologist evaluation
      corroborated by neuroimaging when deemed appropriate, was considered the
      reference standard. Sensitivity and specificity of STANDING were calculated. On
      the first 30 patients, inter-observer agreement among EPs was also assessed.
      RESULTS: Five EPs with limited experience in nystagmus assessment volunteered to
      participate in the present study enrolling 98 patients. Their average evaluation
      time was 9.9 +/- 2.8 min (range 6-17). Central acute vertigo was suspected in 16
      (16.3%) patients. There were 13 true positives, three false positives, 81 true
      negatives and one false negative, with a high sensitivity (92.9%, 95% CI 70-100%)
      and specificity (96.4%, 95% CI 93-38%) for central acute vertigo according to
      senior audiologist evaluation. The Cohen's kappas of the first, second, third and
      fourth steps of the STANDING were 0.86, 0.93, 0.73 and 0.78, respectively. The
      whole test showed a good inter-observer agreement (k = 0.76, 95% CI 0.45-1).
      CONCLUSIONS: In the hands of EPs, STANDING showed a good inter-observer agreement
      and accuracy validated against the local standard of care.

PMID- 25756711
TI  - [Iron deficiency and iron deficiency anemia are global health problems].
AB  - Iron deficiency and iron deficiency anemia are global health problems leading to
      deterioration in patients' quality of life and more serious prognosis in patients
      with chronic diseases. The cause of iron deficiency and anemia is usually a
      combination of increased loss and decreased intestinal absorption and delivery
      from iron stores due to inflammation. Oral iron is first line treatment, but
      often hampered by intolerance. Intravenous iron is safe, and the preferred
      treatment in patients with chronic inflammation and bowel diseases. The goal of
      treatment is normalisation of hemoglobin concentration and recovery of iron
      stores. It is important to follow up treatment to ensure that these objectives
      are met and also long-term in patients with chronic iron loss and/or inflammation
      to avoid recurrence of anemia.

PMID- 25756712
TI  - [Common condition that must not be ignored].

PMID- 25756713
TI  - [Iron supplementation is recommended in renal anemia].
AB  - The main causes for renal anemia are insufficient erythropoietin production and
      absolute and/or functional iron deficiency. Absolute iron deficiency occurs with
      blood losses (most common are gastro-intestinal bleedings and hemodialysis
      treatments) or inadequate iron absorption in the gut (mainly due to increased
      circulating hepcidin or treatment with erythropoiesis stimulating agents). The
      explanation for functional iron deficiency is the high level of circulating
      hepcidin found in chronic kidney disease patients. The transmembrane iron
      transporter ferroportin is internalized and degraded by hepcidin with subsequent
      decreased iron absorption from the gut and reduced mobilization from iron storing
      cells. Thus, the bioavailability of iron is decreased despite normal or high
      total iron content. The diagnosis of iron deficiency in chronic kidney disease
      can be problematic because inflammation is common, leading to false high
      circulating ferritin and false low transferrin saturation. Treatment with iron is
      recommended in chronic kidney disease patients to prevent or minimize anemia
      symptoms or to reduce the need for treatment with erythropoiesis stimulating
      agents or blood transfusions. Intravenous iron is recommended in patients on
      dialysis treatment but in non-dialysis patients, a 1-3 month trial of oral iron
      can be tried. However, this is seldom sufficient in patients treated with
      erythropoiesis stimulating agents. 

PMID- 25756714
TI  - [The patient's right to correct information. No, heart disease will not be
      eradicated].

PMID- 25756715
TI  - [Online magazine combines culture with medicine].

PMID- 25756716
TI  - [Maternity rounds can with limited resources strengthen mothers who want to
      breastfeed].

PMID- 25756717
TI  - [Suggestion to the Swedish Medical Association: Provide support for those accused
      of medical errors].

PMID- 25756718
TI  - [Reply from Heidi Stensmyren: The Swedish Medical Association is active but can
      not be representative].

PMID- 25756719
TI  - [In with updated medical knowledge when ADHD is managed].

PMID- 25756720
TI  - [Reply about "unethical language"].

PMID- 25756721
TI  - [Final reply from Michael Wilczek and Pelle Gustafsson: Alike is not always the
      same].

PMID- 25756722
TI  - [Reply to Hans Wingstrand et al regarding healthcare IT systems: "Important to
      balance patient safety and privacy"].

PMID- 25756723
TI  - [Curiosity without borders. Aldous Huxley tried hallucinogens to look towards
      another world].

PMID- 25756724
TI  - [Healthcare IT systems and doctors' influence].

PMID- 25756725
TI  - [National drug strategy work continues].

PMID- 25756727
TI  - [Speaking! The return of remains--"Ghosts" at Karolinska?].

PMID- 25756728
TI  - [E-health improving].

PMID- 25756729
TI  - [Reply to Assar Horn: Never right to deviate from the principle of human equality
      ].

PMID- 25756730
TI  - [Non smoking goal indisputable but the way getting there should be discussed].

PMID- 25756731
TI  - Factors related to self-efficacy among men and women undergoing outpatient
      chemotherapy in Japan.
AB  - OBJECTIVE: This study aims to examine factors that influence self-efficacy in
      Japanese patients with cancer receiving outpatient chemotherapy and to identify
      whether there are gender-specific similarities or differences that determine self
      efficacy in this setting. METHODS: A cross-sectional survey was conducted among
      156 patients with cancer (86 men and 70 women) undergoing chemotherapy as
      outpatients across five hospitals in Japan. The patients completed the European
      Organization for Research and Cancer Core Quality of Life questionnaire (EORTC
      QLQ-C30), the Self-Efficacy for Advanced Cancer questionnaire (SEAC) which
      consists of three subscales (affect regulation efficacy, symptom-coping efficacy
      and activities of daily living efficacy), and a patient information form.
      Multiple regression analysis was conducted to identify factors associated with
      self-efficacy in men and women. RESULTS: In both men and women, insomnia was
      related to affect regulation efficacy, while fatigue and nausea/vomiting
      correlated with activities of daily living efficacy. For male patients, fatigue
      and nausea/vomiting also correlated with affect regulation efficacy and symptom
      coping efficacy. Emotional functioning influenced self-efficacy for both genders,
      while physical functioning affected self-efficacy in female patients only.
      CONCLUSIONS: These results suggest that to enhance self-efficacy in Japanese
      patients with cancer undergoing outpatient chemotherapy, effective intervention
      is required with regard to the management of both emotional and physical
      functioning, specifically symptoms such as fatigue, nausea/vomiting and insomnia
      in both genders. Furthermore, women with a reduced level of physical function may
      require particular attention, as they may be at risk of lower levels of self
      efficacy.

PMID- 25756732
TI  - Drivers of hospitalization cost after craniotomy for tumor resection: creation
      and validation of a predictive model.
AB  - BACKGROUND: The economic sustainability of all areas of medicine is under
      scrutiny. Limited data exist on the drivers of cost after a craniotomy for tumor
      resection (CTR). The objective of the present study was to develop and validate a
      predictive model of hospitalization cost after CTR. METHODS: We performed a
      retrospective study involving CTR patients who were registered in the Nationwide
      Inpatient Sample (NIS) database from 2005-2010. This cohort underwent 1:1
      randomization to create derivation and validation subsamples. Regression
      techniques were used for the creation of a parsimonious predictive model.
      RESULTS: Of the 36,433 patients undergoing CTR, 14638 (40.2%) underwent
      craniotomies for primary malignant, 9574 (26.3%) for metastatic, and 11414
      (31.3%) for benign tumors. The median hospitalization cost was $24,504
      (Interquartile Range (IQR), $4,265-$44,743). Common drivers of cost identified in
      the multivariate analyses included: length of stay, number of procedures,
      hospital size and region, and patient income. The models were validated in
      independent cohorts and demonstrated final R2 very similar to the initial models.
      The predicted and observed values in the validation cohort demonstrated good
      correlation. CONCLUSIONS: This national study identified significant drivers of
      hospitalization cost after CTR. The presented model can be utilized as an adjunct
      in the cost containment debate and the creation of data-driven policies.

PMID- 25756733
TI  - Considering potential benefits and consequences of hospital report cards: what
      are the next steps?

PMID- 25756735
TI  - Impact of enzyme- and ultrasound-assisted extraction methods on biological
      properties of red, brown, and green seaweeds from the central west coast of
      Portugal.
AB  - Seaweeds are an excellent source of bioactive compounds, and therefore the use of
      sustainable and food compatible extraction methods such as enzyme-assisted (EAE)
      and ultrasound-assisted extraction were applied on Sargassum muticum, Osmundea
      pinnatifida, and Codium tomentosum. Extracts were evaluated for proximate
      characterization and biological properties. Higher extraction yields were
      observed for C. tomentosum EAE (48-62%; p < 0.05 for Cellulase and Viscozyme),
      followed by O. pinnatifida (49-55%; p < 0.05 except Alcalase) and S. muticum (26
      31%; p < 0.05). S. muticum extracts presented the highest nitrogen (25 +/- 2
      mg/glyoph extract) and total phenolics (261 +/- 37 MUgcatechol equiv/glyoph
      extract) contents, whereas higher sugars (78 +/- 14 mgglucose equiv/glyoph
      extract) including sulfated polysaccharide (44 +/- 8 mgNa2SO4 acid/glyoph
      extract) contents characterized O. pinnatifida extracts. A higher effect on
      hydroxyl-radical scavenging activity (35-50%) was observed for all extracts,
      whereas S. muticum Alcalase and C. tomentosum Cellulase extracts exhibited higher
      prebiotic activity than fructooligosaccharides. O. pinnatifida and C. tomentosum
      EAE showed inhibitory potential against alpha-glucosidase (38-49%).

PMID- 25756737
TI  - Solvated graphene frameworks as high-performance anodes for lithium-ion
      batteries.
AB  - A solvent-exchange approach for the preparation of solvated graphene frameworks
      as high-performance anode materials for lithium-ion batteries is reported. The
      mechanically strong graphene frameworks exhibit unique hierarchical solvated
      porous networks and can be directly used as electrodes with a significantly
      improved electrochemical performance compared to unsolvated graphene frameworks,
      including very high reversible capacities, excellent rate capabilities, and
      superior cycling stabilities. 

PMID- 25756736
TI  - Endocytotic uptake of zoledronic acid by tubular cells may explain its renal
      effects in cancer patients receiving high doses of the compound.
AB  - Zoledronic acid, a highly potent nitrogen-containing bisphosphonate used for the
      treatment of pathological bone loss, is excreted unmetabolized via the kidney if
      not bound to the bone. In cancer patients receiving high doses of the compound
      renal excretion may be associated with acute tubular necrosis. The question of
      how zoledronic acid is internalized by renal tubular cells has not been answered
      until now. In the current work, using a primary human tubular cell culture
      system, the pathway of cellular uptake of zoledronic acid
      (fluorescently/radiolabeled) and its cytotoxicity were investigated. Previous
      studies in our laboratory have shown that this primary cell culture model
      consistently mimics the physiological characteristics of molecular
      uptake/transport of the epithelium in vivo. Zoledronic acid was found to be taken
      up by tubular cells via fluid-phase-endocytosis (from apical and basolateral
      side) as evidenced by its co-localization with dextran. Cellular uptake and the
      resulting intracellular level was twice as high from the apical side compared to
      the basolateral side. Furthermore, the intracellular zoledronic acid level was
      found to be dependent on the administered concentration and not saturable.
      Cytotoxic effects however, were only seen at higher administration doses and/or
      after longer incubation times. Although zoledronic acid is taken up by tubular
      cells, no net tubular transport could be measured. It is concluded that fluid
      phase-endocytosis of zoledronic acid and cellular accumulation at high doses may
      be responsible for the acute tubular necrosis observed in some cancer patients
      receiving high doses of the compound. 

PMID- 25756738
TI  - N-[4-(4,6-Dimethyl-2-pyrimidinyloxy)-3-methylphenyl]-N'-[2-(dimethylamino)]
      benzoylurea induces cell-cycle arrest and apoptosis in human cancer cells.
AB  - N-[4-(4,6-Dimethyl-2-pyrimidinyloxy)-3-methylphenyl]-N'-[2
      (dimethylamino)]benzoylurea (SUD) is a novel synthesized benzoylurea derivative.
      We selected several human cancer cell lines to investigate whether SUD can
      inhibit the growth of cancer cells. We selected the liver cell line L-02 to
      investigate the effect of SUD on the normal cells. Flow cytometric analysis was
      used to detect the effect of SUD on cell cycle, Hoechst 33258 staining was used
      to evaluate the apoptosis induced by SUD, real-time fluorescence quantitative PCR
      was used to investigate the expression of the cell cycle-relevant and apoptosis
      relevant genes, a reactive oxygen species (ROS) assay was used to observe the
      production of ROS, and western blotting was used to determine the level of cell
      cycle-relevant and apoptosis-relevant proteins. According to the results of the
      MTT assay, the growth of human cancer cell lines was significantly inhibited by
      SUD treatment in a time-dependent and concentration-dependent manner; however,
      the growth of human normal cells was not significantly inhibited by SUD
      treatment. The results of flow cytometric analyses showed that SUD induced cell
      cycle arrest at the G2-phase in MCF-7 cells and at the G1-phase in BGC-823 cells.
      The results of Hoechst 33258 staining showed that SUD induced apoptosis in MCF-7
      and BGC-823 cells. The results of the ROS assay showed that the production of ROS
      was increased by SUD in MCF-7 and BGC-823 cells. Our research suggests that the
      growth-inhibitory effect of SUD on MCF-7 cells was related to G2-phase arrest,
      which was associated with the upregulated expression of p53 and Chk1 proteins,
      and downregulation of the cyclin B1 gene, cdc25a, and cyclin-dependent kinase 1
      (CDK1) proteins; the growth-inhibitory effect of SUD on BGC-823 cells was related
      to G1-phase arrest, which was associated with upregulation of the p53 gene and
      Chk1 protein and downregulation of cdc25a protein and the CDK4 gene. SUD also
      induced apoptosis in MCF-7 and BGC-823 cell lines through the mitochondrial
      pathway in a p53-dependent manner. 

PMID- 25756739
TI  - Why are we not doing more for alcohol use disorder among conflict-affected
      populations?

PMID- 25756740
TI  - Informed consent procedures with cognitively impaired patients: A review of
      ethics and best practices.
AB  - AIMS: The objectives of this article are to discuss ethical issues of informed
      consent in cognitively impaired patients and review considerations for capacity
      determination. We will also discuss how to evaluate capacity, determine
      competence, and obtain informed consent when a patient is deemed incompetent.
      This review emphasizes how to carry out informed consent procedures when capacity
      is questionable and discusses measures supported for use when determining
      cognitively impaired patients' ability to consent. METHODS: Information was
      gathered from medical and psychological codes of ethics, peer-reviewed journals,
      published guidelines from health-care organizations (e.g., American Medical
      Association), and scholarly books. Google Scholar and PsycINFO were searched for
      articles related to 'informed consent' and 'cognitive impairment' published in
      English between 1975 and 2014. Relevant sources referenced in retrieved
      publications were subsequently searched and reviewed. RESULTS: We selected 49
      sources generated by our search. Sources were included in our review if they
      presented information related to at least one of our focus areas. These areas
      included: review of informed consent ethics and procedures, review of cognitive
      impairment evaluations, recommendations for measuring cognitive capacity, and
      alternative forms of informed consent. CONCLUSIONS: Patients' cognitive
      impairments can hinder the ability of patients to understand treatment options.
      Evaluating the capacity of patients with cognitive impairment to understand
      treatment options is vital for valid informed consent and should be guided by
      best practices. Thus, proper identification of patients with questionable
      capacity, capacity evaluation, and determination of competence, as well as
      reliance upon appropriate alternative consent procedures, are paramount.

PMID- 25756741
TI  - Evolution of tinea capitis in the Nanchang area, Southern China: a 50-year survey
      (1965-2014).
AB  - Tinea capitis remains a common public health problem worldwide especially in
      developing areas. Aetiologic agents and clinical pattern vary with geography and
      history of socioeconomic conditions. Three community surveys and a prospective
      study were carried out over the past 50 years (1965-2014) in the Qingyunpu
      District of Nanchang, Southern China. Clinical presentation and spectrum of
      aetiological agents were monitored to understand the evolution of tinea capitis.
      In 1965 favus was highly epidemic and Trichophyton schoenleinii presented as the
      overwhelming aetiological agents of scalp infection in the study area, with a
      prevalence of 3.41% of the population. During a governmental campaign to
      eliminate tinea capitis initiated in mid of 1960s, favus was successfully
      controlled and the prevalence decreased to less than 0.01% in 1977. After that
      period, clinical presentation and spectrum of fungi changed with social
      development. Trichophyton schoenleinii was replaced by Trichophyton violaceum and
      Trichophyton mentagrophytes. Nowadays, the species corresponds with a dominant
      black dot type of tinea capitis in the Nanchang area. The prevalence of causative
      agents of tinea capitis is not only related to geography but also to
      socioeconomic factors. Multiple factors have to be considered for the management
      for control of this disease. 

PMID- 25756743
TI  - Hypertension in african americans aged 60 to 79 years: statement from the
      international society of hypertension in blacks.
AB  - A 2014 hypertension guideline raised goal systolic blood pressure (SBP) from <140
      mm Hg to <150 mm Hg for adults 60 years and older without diabetes mellitus (DM)
      or chronic kidney disease (CKD). The authors aimed to define the status of
      hypertension in black adults 60 to 79 years from the National Health and
      Nutrition Examination Survey 2005-2012 and provide practical guidance. Black
      patients were more often aware and treated (P<=.005) for hypertension than whites
      and had higher rates of DM/CKD (P<.001), similar control to <140/<90 mm Hg with
      DM/CKD (P=.59), and lower control without DM/CKD (<140/<90 mm Hg and <150/<90 mm
      Hg, P<=.01). Limited awareness (<30%) and infrequent health care (>30% 0-1 health
      care visits per year) occurred in untreated black and white hypertensive patients
      without DM/CKD and BP >=140/<90 mm Hg. The literature suggests benefits of
      treated SBP <140 mm Hg in adults 60 to 79 years without DM/CKD. The International
      Society of Hypertension in Blacks recommends: (1) continuing efforts to achieve
      BP <140/<90 mm Hg in those with DM/CK, and (2) identifying hypertensive patients
      without DM/CKD and BP >=140/<90 mm Hg and treat to an SBP <140 mm Hg in black
      adults 60-79 years. 

PMID- 25756742
TI  - Switching to second-generation tyrosine kinase inhibitor improves the response
      and outcome of frontline imatinib-treated patients with chronic myeloid leukemia
      with more than 10% of BCR-ABL/ABL ratio at 3 months.
AB  - Chronic myeloid leukemia patients display heterogeneous responses to imatinib.
      Survival depends on baseline clinical characteristics (including prognostic
      scoring systems) and on early response (such as >10% BCR-ABL/ABL ratio at 3
      months of therapy). The results of switching to second-generation tyrosine kinase
      inhibitors (2GTKIs) may contain a bias since, in the majority of these studies,
      patients who switch treatment due to intolerance or failure are censored or
      excluded. We analyzed the Spanish Registry data on switching in an intention-to
      treat analysis of patients in standard clinical practice. Switching to 2GTKIs
      improves responses from 45% to 75% of complete cytogenetic response (CCyR) and
      from 15% to 45% of major molecular response (MMR) in the group without molecular
      response 1 (MR1) at 3 months and from 70% to 87% in CCyR and from 52% to 87% in
      MMR in the group with MR1. The final response rate is poorer in the group with no
      MR1 at 3 months. Nevertheless, the differences in the rates of response were not
      translated into differences in major events (transformations or deaths), and the
      final progression-free survival and overall survival were similar. 

PMID- 25756744
TI  - Feeding laying hens stearidonic acid-enriched soybean oil, as compared to
      flaxseed oil, more efficiently enriches eggs with very long-chain n-3
      polyunsaturated fatty acids.
AB  - The desaturation of alpha-linolenic acid (ALA) to stearidonic acid (SDA) is
      considered to be rate-limiting for the hepatic conversion of ALA to
      eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in humans, rodents,
      and chickens. Thus, we hypothesized that feeding laying hens SDA, as a component
      of the oil derived from the genetic modification of the soybean, would bypass
      this inefficient metabolic step and result in the enrichment of eggs with EPA and
      DHA at amounts comparable to that achieved by direct supplementation of hens'
      diet with these very long-chain (VLC) n-3 polyunsaturated fatty acids (PUFAs). In
      a 28-d study, laying hens incorporated 0.132 mg, 0.041 mg, or 0.075 mg of VLC n-3
      PUFAs into egg yolk for each milligram of ingested dietary ALA derived primarily
      from conventional soybean oil (CON), dietary ALA derived primarily from flaxseed
      oil (FLAX), or dietary SDA derived from SDA-enriched soybean oil, respectively.
      Moreover, the amounts of total yolk VLC n-3 PUFAs in eggs from hens fed the CON
      (51 mg), FLAX (91 mg), or SDA (125 mg) oils were markedly less than the 305 mg
      found in eggs from fish oil-fed hens. Unexpectedly, SDA appeared to be more
      readily incorporated into adipose tissue than into egg yolk. Since egg yolk FAs
      typically reflect the hens' dietary pattern, these tissue-specific differences
      suggest the existence of an alternate pathway for the hepatic secretion and
      transport of SDA in the laying hen. 

PMID- 25756745
TI  - Characteristics of female mentally disordered offenders culpable under the new
      legislation in Japan: A gender comparison study.
AB  - BACKGROUND: Although a substantial increase in the number of female offenders has
      drawn interest towards understanding their unique characteristics, few studies
      have investigated the characteristics of female mentally disordered offenders in
      Japan and none since the legislation enacted in 2005 in Japan, which provided for
      special services for them. AIMS: The aim of this study is to identify those
      characteristics of people detained under this legislation, which distinguish the
      women from the men and may indicate special needs among the women. METHODS: A
      retrospective records-based study of all patients admitted to one secure unit in
      the 8 years since its opening in July 2005 until a census date of 31 October
      2013. RESULTS: Thirty-six (15%) of the patients were women. Marriage, mood
      disorders, past suicide attempts and homicide were more common among the women
      than the men. Six of the female offender-patients had committed filicides, of
      which four were infanticides. CONCLUSION: There appears to be a particularly
      vulnerable sub-group of women with severe mood disorders, a history of serious
      suicide attempts and young children at risk of harming those children. Our sample
      was small and from a single unit so, given the potential importance of improving
      understanding of who is at risk in such circumstances, extending our study
      nationally seems indicated.

PMID- 25756746
TI  - Transaortic TAVI Is a Valid Alternative to Transapical Approach.
AB  - BACKGROUND AND AIM: Transcatheter aortic valve implantation (TAVI) can be
      performed via a number of different anatomical approaches based on patient
      characteristics and operator choice. The aim of this study was to compare
      procedural outcomes between transaortic (TAo) and transapical (TA) approaches in
      an effort to establish whether any differences exist. METHODS: A systematic
      review and meta-analysis of the current literature reporting outcomes for
      patients undergoing TAo and TA TAVI was performed to compare outcomes using each
      vascular approach to valve deployment. RESULTS: A total of 10 studies and 1736
      patients were included. A total of 193 patients underwent TAo and 1543 TA TAVI.
      No significant difference in 30-day mortality was identified (TAo 9.4, TA 10.4 p
      = 0.7). There were no significant differences identified between TAo and TA TAVI
      in procedural success rate (96.3% vs. 93.7% p = 0.3), stroke and transient
      ischemic attack (TIA) incidence (1.8% vs. 2.3% p = 0.7), major bleed (5.8% vs.
      5.5% p = 0.97) or pacemaker insertion rates (6.1% vs. 7.4% p = 0.56). In
      addition, the incidence of clinically significant paravalvular regurgitation
      (PVR) was the same between groups (6.7% vs. 11% p = 0.43). CONCLUSION: Comparison
      of TAo and TA approaches revealed equivalent outcomes in 30-day mortality,
      procedural success, major bleeding, stroke/TIA incidence, pacemaker insertion
      rates and paravalvular leak. Heart teams should be familiar with the use of both
      TA and TAo access and tailor their selection on a case-to-case basis.

PMID- 25756747
TI  - Analysis of the viral replication cycle of adenovirus serotype 2 after
      inactivation by free chlorine.
AB  - Free chlorine is effective at inactivating a wide range of waterborne viral
      pathogens including human adenovirus (HAdV), but the mechanisms by which free
      chlorine inactivates HAdV and other human viruses remain to be elucidated. Such
      advances in fundamental knowledge are key for development of new disinfection
      technologies and novel sensors to detect infectious viruses in drinking water. We
      developed and tested a quantitative assay to analyze several steps in the HAdV
      replication cycle upon increasing free chlorine exposure. We used quantitative
      polymerase chain reaction (qPCR) to detect HAdV genomic DNA as a means to
      quantify attachment and genome replication of untreated and treated virions.
      Also, we used quantitative reverse-transcription PCR (RT-qPCR) to quantify the
      transcription of E1A (first early protein) and hexon mRNA. We compared these
      replication cycle events to virus inactivation kinetics to determine what stage
      of the virus replication cycle was inhibited as a function of free chlorine
      exposure. We observed that adenovirus inactivated at levels up to 99.99% by free
      chlorine still attached to host cells; however, viral DNA synthesis and early E1A
      and late hexon gene transcription were inhibited. We conclude that free chlorine
      exposure interferes with a replication cycle event occurring postbinding but
      prior to early viral protein synthesis. 

PMID- 25756748
TI  - Ups and downs in the search for a Herpes simplex virus vaccine.
AB  - Modified herpes simplex viruses that are unable to produce glycoprotein D may
      make effective vaccines. 

PMID- 25756749
TI  - The menagerie of human lipocalins: a natural protein scaffold for molecular
      recognition of physiological compounds.
AB  - While immunoglobulins are well-known for their characteristic ability to bind
      macromolecular antigens (i.e., as antibodies during an immune response), the
      lipocalins constitute a family of proteins whose role is the complexation of
      small molecules for various physiological processes. In fact, a number of low
      molecular-weight substances in multicellular organisms show poor solubility, are
      prone to chemical decomposition, or play a pathophysiological role and thus
      require specific binding proteins for transport through body fluids, storage, or
      sequestration. In many cases, lipocalins are involved in such tasks. Lipocalins
      are small, usually monomeric proteins with 150-180 residues and diameters of
      approximately 40 A, adopting a compact fold that is dominated by a central eight
      stranded up-and-down beta-barrel. At the amino-terminal end, this core is flanked
      by a coiled polypeptide segment, while its carboxy-terminal end is followed by an
      alpha-helix that leans against the beta-barrel as well as an amino acid stretch
      in a more-or-less extended conformation, which finally is fixed by a disulfide
      bond. Within the beta-barrel, the antiparallel strands (designated A to H) are
      arranged in a (+1)7 topology and wind around a central axis in a right-handed
      manner such that part of strand A is hydrogen-bonded to strand H again. Whereas
      the lower region of the beta-barrel is closed by short loops and densely packed
      hydrophobic side chains, including many aromatic residues, the upper end is
      usually open to solvent. There, four long loops, each connecting one pair of beta
      strands, together form the entrance to a cup-shaped cavity. Depending on the
      individual structure of a lipocalin, and especially on the lengths and amino acid
      sequences of its four loops, this pocket can accommodate chemical ligands of
      various sizes and shapes, including lipids, steroids, and other chemical hormones
      as well as secondary metabolites such as vitamins, cofactors, or odorants. While
      lipocalins are ubiquitous in all higher organisms, physiologically important
      members of this family have long been known in the human body, for example with
      the plasma retinol-binding protein that serves for the transport of vitamin A.
      This prototypic human lipocalin was the first for which a crystal structure was
      solved. Notably, several other lipocalins were discovered and assigned to this
      protein class before the term itself became familiar, which explains their
      diverse names in the scientific literature. To date, up to 15 distinct members of
      the lipocalin family have been characterized in humans, and during the last two
      decades the three-dimensional structures of a dozen major subtypes have been
      elucidated. This Account presents a comprehensive overview of the human
      lipocalins, revealing common structural principles but also deviations that
      explain individual functional features. Taking advantage of modern methods for
      combinatorial protein design, lipocalins have also been employed as scaffolds for
      the construction of artifical binding proteins with novel ligand specificities,
      so-called Anticalins, hence opening perspectives as a new class of
      biopharmaceuticals for medical therapy. 

PMID- 25756750
TI  - Dosimetry for infant exposures to electronic article surveillance system:
      posture, physical dimension and anatomy.
AB  - The use of electronic article surveillance (EAS) systems has become popular in
      many public sites. As a consequence, concern has risen about infant exposure to
      magnetic fields (MFs) from this kind of device. To evaluate infant exposure to
      MFs of an EAS system (operating at 125 kHz and 13.56 MHz), we numerically
      compared dosimetric results among adult, child and infant models. Results
      revealed that postures insignificantly influenced dosimetric results if there was
      a similar cross-sectional area under exposure. Although safety limits are
      unlikely to be exceeded, the infant has higher SAR values for brain and central
      nervous system tissues compared with adult (1.5x at 125 kHz and 112x at 13.56
      MHz), which deserve further investigation. Infant's specific anatomy (e.g., non
      proportionally large head and high fat content) did not induce higher SAR values.
      The numerical models developed in the study (stroller and postured infant models)
      could be freely used for nonprofit academic research.

PMID- 25756751
TI  - Factors differentially associated with early readmission at a university teaching
      psychiatric hospital.
AB  - RATIONALE, AIMS AND OBJECTIVES: The rate of psychiatric readmissions within 30
      days of discharge is a well-established behavioural health system performance
      measure linked to the quality of inpatient hospital care as well as to access to
      community-based aftercare services. The purpose of this study was to examine the
      factors differentially associated with earlier readmission among a sample of
      patients (n = 588) readmitted within 30 days of discharge to a university
      teaching psychiatric hospital from 2001 to 2010. METHODS: Quality assurance
      interviews were conducted with patients readmitted within 30 days of discharge.
      The interview data were merged with clinical symptom and electronic medical
      record data. Multinomial logistic regression analysis was used to examine
      readmission within 7 days and from 8 to 14 days compared with 15-30 days after
      discharge while controlling for socio-demographic and treatment variables
      previously associated with psychiatric readmission. RESULTS: Multiple clinical,
      treatment and patient-reported factors were differentially associated with
      earlier readmission. In particular, lack of engagement in post-discharge
      aftercare services was a strong predictor of earlier readmission. CONCLUSIONS:
      Strategies are needed to improve patients' transition from inpatient psychiatric
      hospitalization to aftercare services. Psychiatric hospitals attempting to reduce
      very early readmissions should seek to implement innovative transitional care
      initiatives targeting both patient and treatment factors.

PMID- 25756752
TI  - Theoretical study of acene-bridged dyes for dye-sensitized solar cells.
AB  - The electronic structures and absorption spectra for a series of acene-based
      organic dyes and the adsorption energy and optical properties for these dyes
      adsorbed on (TiO2)38 have been investigated using density functional theory (DFT)
      and time-dependent density functional theory (TDDFT) methods. The effects of
      acene units and different substitution positions of electron donors on the
      optoelectronic properties of the acene-modified dyes are demonstrated. The
      photophysical properties of tetracene- and pentacene-based dyes are found to be
      tuned by changing the size of acene and the substitution position of the donor.
      The donor sites have a significant influence on the absorption wavelength mainly
      because of different molecular orbital (MO) contributions of the highest occupied
      molecular orbital (HOMO) on the bridging acene units, and the increasing MO
      contribution would lead to the red shift in the absorption spectra. Meanwhile,
      the donor is located close to the center of the pi-conjugated bridge, and the
      absorption spectra are extended. The adsorption energy and optical properties of
      tetracene- and pentacene-based dyes adsorbed on (TiO2)38 suggest that acene
      bridged dyes could be adsorbed on the TiO2 surface and inject electrons into
      semiconductors effectively. Then the results obtained from the hexacene-based
      dyes confirm the conclusions proposed from the tetracene- and pentence-based
      dyes. This study will provide a useful reference to the future design and
      optimization of acene dyes for dye-sensitized solar cell applications. 

PMID- 25756753
TI  - Unique hydrogen-bonded complex of hydronium and hydroxide ions.
AB  - H3 O(+) and OH(-) , formed by the self-ionization of two coordinating water
      molecules during the crystal growing of a host molecule [1,3,5
      tris(hydroxymethyl)2,4,6-triethylbenzene (1)], could be effectively stabilized by
      hydrogen-bonding interactions with the preorganized hydroxy groups of three
      molecules of 1. The binding motifs observed in the complex (1)3 ?H3 O(+) ?HO(-)
      show remarkable similarity to those postulated for the hydrated hydronium and
      hydroxide ion complexes, which play important roles in various chemical,
      biological, and atmospheric processes, but their molecular structures are still
      not fully understood and remain a subject of intensive research. 

PMID- 25756754
TI  - Correction to "chemoselective synthesis of sialic Acid 1,7-lactones".

PMID- 25756755
TI  - Research fellowship programs as a pathway for training independent clinical
      pharmacy scientists.
AB  - The American College of Clinical Pharmacy (ACCP) Research Affairs Committee
      published a commentary in 2013 on training clinical pharmacy scientists in the
      context of changes in economic, professional, political, and research
      environments. The commentary centered on the opportunities for pharmacists in
      clinical/translational research including strategies for ACCP, colleges of
      pharmacy, and the profession to increase the number and impact of clinical
      pharmacy scientists. A postdoctoral fellowship is cited as a current training
      pathway, capable of producing independent and productive pharmacy researchers.
      However, a decline in the number of programs, decreased funding availability, and
      variability in fellowship program activities and research focus have brought into
      question the relevance of this research training pathway to meet demand and
      opportunities. In response to these points, this commentary examines the state of
      research fellowship training including the current ACCP research fellowship
      review process, the need for standardization of research fellowship programs, and
      strategies to strengthen and promote research fellowships as relevant researcher
      training pathways. 

PMID- 25756756
TI  - Mechanisms of heme utilization by Francisella tularensis.
AB  - Francisella tularensis is a highly virulent facultative intracellular pathogen
      causing the severe disease tularemia in mammals. As for other bacteria, iron is
      essential for its growth but very few mechanisms for iron acquisition have been
      identified. Here, we analyzed if and how F. tularensis can utilize heme, a major
      source of iron in vivo. This is by no means obvious since the bacterium lacks
      components of traditional heme-uptake systems. We show that SCHU S4, the
      prototypic strain of subspecies tularensis, grew in vitro with heme as the sole
      iron source. By screening a SCHU S4 transposon insertion library, 16 genes were
      identified as important to efficiently utilize heme, two of which were required
      to avoid heme toxicity. None of the identified genes appeared to encode
      components of a potential heme-uptake apparatus. Analysis of SCHU S4 deletion
      mutants revealed that each of the components FeoB, the siderophore system, and
      FupA, contributed to the heme-dependent growth. In the case of the former two
      systems, iron acquisition was impaired, whereas the absence of FupA did not
      affect iron uptake but led to abnormally high binding of iron to macromolecules.
      Overall, the present study demonstrates that heme supports growth of F.
      tularensis and that the requirements for the utilization are highly complex and
      to some extent novel. 

PMID- 25756757
TI  - Nitrogen enriched mesoporous organic polymer anchored copper(II) material: an
      efficient and reusable catalyst for the synthesis of esters and amides from
      aromatic systems.
AB  - A new copper-grafted mesoporous poly-melamine-formaldehyde (Cu-mPMF) has been
      synthesized from melamine and paraformaldehyde in DMSO medium, followed by
      grafting of Cu(ii) at its surface. Cu-mPMF has been characterized by elemental
      analysis, powder XRD, HR TEM, FE-SEM, N2 adsorption study, FT-IR, UV-vis DRS, TGA
      DTA, EPR spectroscopy, Raman spectroscopy and X-ray photoelectron spectroscopy
      (XPS). The Cu-grafted mesoporous material showed very good catalytic activity in
      methyl esterification of benzylic alcohols and amidation of nitriles. Moreover,
      the catalyst is easily recoverable and can be reused seven times without
      appreciable loss of catalytic activity in the above reactions. The highly
      dispersed and strongly bound Cu(ii) sites in the Cu-grafted mesoporous polymer
      could be responsible for the observed high activities of the Cu-mPMF catalyst.
      Due to strong binding with the functional groups of the polymer, no evidence of
      leached copper from the catalyst during the course of reaction emerged,
      suggesting true heterogeneity in the catalytic process. 

PMID- 25756758
TI  - Surface passivation improves the synthesis of highly stable and specific DNA
      functionalized gold nanoparticles with variable DNA density.
AB  - We report a novel and multifaceted approach for the quick synthesis of highly
      stable single-stranded DNA (ssDNA) functionalized gold nanoparticles (AuNPs). The
      method is based on the combined effect of surface passivation by (1-mercaptoundec
      11-yl)hexa(ethylene glycol) and low pH conditions, does not require any salt
      pretreatment or high excess of ssDNA, and can be generalized for oligonucleotides
      of any length or base sequence. The synthesized ssDNA-coated AuNPs conjugates are
      stable at salt concentrations as high as 3.0 M, and also functional and specific
      toward DNA-DNA hybridization, as shown from UV-vis spectrophotometry, scanning
      electron microscopy, gel electrophoresis, fluorescence, and small angle X-ray
      scattering based analyses. The method is highly flexible and shows an additional
      advantage of creating ssDNA-AuNP conjugates with a predefined number of ssDNA
      strands per particle. Its simplicity and tenability make it widely applicable to
      diverse biosensing applications involving ssDNA functionalized AuNPs. 

PMID- 25756759
TI  - Antibiotic Resistance of Listeria monocytogenes Isolated from Meat-Processing
      Environments, Beef Products, and Clinical Cases in Brazil.
AB  - The present study aimed to assess the antimicrobial resistance and the presence
      of virulence markers in 137 Listeria monocytogenes isolates obtained from meat
      processing environments, beef products, and clinical cases. All isolates were
      subject to molecular serogrouping and their antibiotic resistance profiles were
      assessed against 12 antimicrobials. In addition, isolates were subjected to
      detection of virulence marker genes (inlA, inlC, inlJ). The isolates were
      classified into serogroups 4b, 4d, 4a, or 4c (46%), 1/2c or 3c (27%), 1/2a or 3a
      (13.9%), and 1/2b or 3b (13.1%). All tested isolates presented sensitivity to the
      majority of the tested antimicrobials, but most of them presented resistance or
      intermediate resistance to clindamycin (88.3%) and oxacillin (73.7%). Virulence
      markers were detected in all isolates, demanding further analysis to better
      characterize their pathogenic potential. 

PMID- 25756760
TI  - A general method for growing large area mesoporous silica thin films on flat
      substrates with perpendicular nanochannels.
AB  - Here we introduce a new synthetic approach to grow mesoporous silica thin films
      with vertical mesochannels on centimeter-sized substrates via an oil-induced co
      assembly process. Adding an oil, i.e., decane, into a CTAB-EtOH-TEOS ammonia
      solution leads to thin-film formation of mesoporous silica of controlled
      thickness between 20 and 100 nm with vertical mesochannels on various surfaces.
      The vertical mesoporous channels were evidenced by grazing incidence small-angle
      X-ray scattering (GISAXS), scanning electron microscopy (SEM), and transmission
      electron microscopy (TEM) characterizations. Decane played two roles: (a) as a
      pore expansion agent (up to 5.7 +/- 0.5 nm) and (b) inducing vertically oriented
      hexagonal mesophases of micelle-silica composite. The production of periodic and
      vertical nanochannels is very robust, over many different substrate surfaces
      (from silicon to polystyrene), various silica precursors (TEOS, fumed silica, or
      zeolite seed), and many oils (decane, petroleum ether, or ethyl acetate). This
      wide robustness in the formation of vertical nanophases is attributed to a unique
      mechanism of confined synthesis of surfactant-silicate between two identical thin
      layers of oils on a substrate. 

PMID- 25756761
TI  - From bench to bedlam.

PMID- 25756762
TI  - Neurobehavioral aspects of multidimensional psychopathology.

PMID- 25756763
TI  - (13)C magnetic resonance spectroscopy and glutamate metabolism in mood disorders:
      current challenges, potential opportunities.

PMID- 25756764
TI  - 2014 in review.

PMID- 25756765
TI  - DSM issues: incorporation of biological tests, avoidance of reification, and an
      approach to the "box canyon problem".

PMID- 25756766
TI  - Expanding the envelope.

PMID- 25756767
TI  - Mercury poisoning: a case of a complex neuropsychiatric illness.

PMID- 25756768
TI  - Tom of Bedlam.

PMID- 25756769
TI  - Brief versus intensive psychosocial treatments for bipolar disorder: time for
      stepped care?

PMID- 25756770
TI  - Response to Parikh.

PMID- 25756771
TI  - Psychotherapy and psychiatric science.

PMID- 25756773
TI  - Correction.

PMID- 25756772
TI  - Ventromedial syndrome with normal cognitive functioning in vascular depression.

PMID- 25756780
TI  - Sustained attention is associated with error processing impairment: evidence from
      mental fatigue study in four-choice reaction time task.
AB  - Attention is important in error processing. Few studies have examined the link
      between sustained attention and error processing. In this study, we examined how
      error-related negativity (ERN) of a four-choice reaction time task was reduced in
      the mental fatigue condition and investigated the role of sustained attention in
      error processing. Forty-one recruited participants were divided into two groups.
      In the fatigue experiment group, 20 subjects performed a fatigue experiment and
      an additional continuous psychomotor vigilance test (PVT) for 1 h. In the normal
      experiment group, 21 subjects only performed the normal experimental procedures
      without the PVT test. Fatigue and sustained attention states were assessed with a
      questionnaire. Event-related potential results showed that ERN (p < 0.005) and
      peak (p < 0.05) mean amplitudes decreased in the fatigue experiment. ERN
      amplitudes were significantly associated with the attention and fatigue states in
      electrodes Fz, FC1, Cz, and FC2. These findings indicated that sustained
      attention was related to error processing and that decreased attention is likely
      the cause of error processing impairment. 

PMID- 25756781
TI  - Nanoscintillator-mediated X-ray inducible photodynamic therapy for in vivo cancer
      treatment.
AB  - Photodynamic therapy is a promising treatment method, but its applications are
      limited by the shallow penetration of visible light. Here, we report a novel X
      ray inducible photodynamic therapy (X-PDT) approach that allows PDT to be
      regulated by X-rays. Upon X-ray irradiation, the integrated nanosystem, comprised
      of a core of a nanoscintillator and a mesoporous silica coating loaded with
      photosensitizers, converts X-ray photons to visible photons to activate the
      photosensitizers and cause efficient tumor shrinkage. 

PMID- 25756782
TI  - Spatial positioning of all 24 chromosomes in the lymphocytes of six subjects:
      evidence of reproducible positioning and spatial repositioning following DNA
      damage with hydrogen peroxide and ultraviolet B.
AB  - The higher-order organization of chromatin is well-established, with chromosomes
      occupying distinct positions within the interphase nucleus. Chromatin is
      susceptible to, and constantly assaulted by both endogenous and exogenous
      threats. However, the effects of DNA damage on the spatial topology of
      chromosomes are hitherto, poorly understood. This study investigates the
      organization of all 24 human chromosomes in lymphocytes from six individuals
      prior to- and following in-vitro exposure to genotoxic agents: hydrogen peroxide
      and ultraviolet B. This study is the first to report reproducible distinct
      hierarchical radial organization of chromosomes with little inter-individual
      differences between subjects. Perturbed nuclear organization was observed
      following genotoxic exposure for both agents; however a greater effect was
      observed for hydrogen peroxide including: 1) More peripheral radial organization;
      2) Alterations in the global distribution of chromosomes; and 3) More events of
      chromosome repositioning (18 events involving 10 chromosomes vs. 11 events
      involving 9 chromosomes for hydrogen peroxide and ultraviolet B respectively).
      Evidence is provided of chromosome repositioning and altered nuclear organization
      following in-vitro exposure to genotoxic agents, with notable differences
      observed between the two investigated agents. Repositioning of chromosomes
      following genotoxicity involved recurrent chromosomes and is most likely part of
      the genomes inherent response to DNA damage. The variances in nuclear
      organization observed between the two agents likely reflects differences in
      mobility and/or decondensation of chromatin as a result of differences in the
      type of DNA damage induced, chromatin regions targeted, and DNA repair
      mechanisms. 

PMID- 25756783
TI  - The effects of reduced gluten barley diet on humoral and cell-mediated systemic
      immune responses of gluten-sensitive rhesus macaques.
AB  - Celiac disease (CD) affects approximately 1% of the general population while an
      estimated additional 6% suffers from a recently characterized, rapidly emerging,
      similar disease, referred to as non-celiac gluten sensitivity (NCGS). The only
      effective treatment of CD and NCGS requires removal of gluten sources from the
      diet. Since required adherence to a gluten-free diet (GFD) is difficult to
      accomplish, efforts to develop alternative treatments have been intensifying in
      recent years. In this study, the non-human primate model of CD/NCGS, e.g., gluten
      sensitive rhesus macaque, was utilized with the objective to evaluate the
      treatment potential of reduced gluten cereals using a reduced gluten (RG; 1% of
      normal gluten) barley mutant as a model. Conventional and RG barleys were used
      for the formulation of experimental chows and fed to gluten-sensitive (GS) and
      control macaques to determine if RG barley causes a remission of dietary gluten
      induced clinical and immune responses in GS macaques. The impacts of the RG
      barley diet were compared with the impacts of the conventional barley-containing
      chow and the GFD. Although remission of the anti-gliadin antibody (AGA) serum
      responses and an improvement of clinical diarrhea were noted after switching the
      conventional to the RG barley diet, production of inflammatory cytokines, e.g.,
      interferon-gamma (IFN-gamma), tumor necrosis factor (TNF) and interleukin-8 (IL
      8) by peripheral CD4+ T helper lymphocytes, persisted during the RG chow
      treatment and were partially abolished only upon re-administration of the GFD. It
      was concluded that the RG barley diet might be used for the partial improvement
      of gluten-induced disease but its therapeutic value still requires upgrading-by
      co-administration of additional treatments. 

PMID- 25756784
TI  - Structures of phytosterols and triterpenoids with potential anti-cancer activity
      in bran of black non-glutinous rice.
AB  - Structures of some bioactive phytochemicals in bran extract of the black rice cv.
      Riceberry that had demonstrated anti-cancer activity in leukemic cell line were
      investigated. After saponification with potassium hydroxide, separation of the
      unsaponified fraction by reversed-phase high performance liquid chromatography
      (HPLC) resulted in four sub-fractions that had a certain degree of anti
      proliferation against a mouse leukemic cell line (WEHI-3 cell), this being IC50
      at 24 h ranging between 2.80-467.11 MUg/mL. Further purification of the bioactive
      substances contained in these four sub-fractions was performed by normal-phase
      HPLC. Structural characterization by gas chromatography-mass spectrometry (GC
      MS), liquid chromatography-mass spectrometry (LC-MS) and nuclear magnetic
      resonance spectroscopy (NMR) resulted in, overall, the structures of seven
      phytosterols and four triterpenoids. Four phytosterols, 24-methylene-ergosta-5-en
      3beta-ol, 24-methylene-ergosta-7-en-3beta-ol, fucosterol, and gramisterol, along
      with three triterpenoids, cycloeucalenol, lupenone, and lupeol, were found in the
      two sub-fractions that showed strong anti-leukemic cell proliferation (IC50 =
      2.80 and 32.89 MUg/mL). The other sterols and triterpenoids were campesterol,
      stigmasterol, beta-sitosterol and 24-methylenecycloartanol. Together with the
      data from in vitro biological analysis, we suggest that gramisterol is a
      significant anti-cancer lead compound in Riceberry bran extract. 

PMID- 25756785
TI  - Epidemiological changes in leishmaniasis in Spain according to hospitalization
      based records, 1997-2011: raising awareness towards leishmaniasis in non-HIV
      patients.
AB  - In Spain, Leishmania infantum is endemic, human visceral and cutaneous
      leishmaniasis cases occurring both in the Peninsula, as well as in the Balearic
      Islands. We aimed to describe the clinical characteristics of leishmaniasis
      patients and the changes in the disease evolution after the introduction of
      antiretroviral therapy in 1997. In this descriptive study, we used Spanish
      Centralized Hospital Discharge Database for the hospitalized leishmaniasis cases
      between 1997 and 2011. We included in the analysis only the records having
      leishmaniasis as the first registered diagnosis and calculated the
      hospitalization rates. Disease trend was described taking into account the HIV
      status. Adjusted odds-ratio was used to estimate the association between clinical
      and socio-demographic factors and HIV co-infection. Of the total 8010
      Leishmaniasis hospitalizations records, 3442 had leishmaniasis as first
      diagnosis; 2545/3442 (75.6%) were males and 2240/3442 (65.1%) aged between 14-65
      years. Regarding disease forms, 2844/3442 (82.6%) of hospitalizations were due to
      visceral leishmaniasis (VL), while 118/3442 (3.4%) hospitalizations were
      cutaneous leishmaniasis (CL). Overall, 1737/2844 of VL (61.1%) were HIV
      negatives. An overall increasing trend was observed for the records with
      leishmaniasis as first diagnosis (p=0.113). Non-HIV leishmaniasis increased
      during this time period (p=0.021) while leishmaniasis-HIV co-infection
      hospitalization revealed a slight descending trend (p=0.717). Leishmaniasis-HIV
      co-infection was significantly associated with male sex (aOR=1.6; 95% CI: 1.25
      2.04), 16-64 years age group (aOR=17.4; 95%CI: 2.1-143.3), visceral leishmaniasis
      aOR=6.1 (95%CI: 3.27-11.28) and solid neoplasms 4.5 (95% CI: 1.65-12.04). The
      absence of HIV co-infection was associated with lymph/hematopoietic neoplasms
      (aOR=0.3; 95%CI:0.14-0.57), other immunodeficiency (aOR=0.04; 95% CI:0.01-0.32)
      and transplant (aOR=0.01; 95%CI:0.00-0.07). Our findings suggest a significant
      increase of hospitalization in the absence of HIV co-infection, with a
      predomination of VL. We consider that clinicians in Spain should be aware of
      leishmaniasis not only in the HIV population but also in non HIV patients,
      especially for those having immunosuppression as an associate condition. 

PMID- 25756786
TI  - High Expression of Mannose-Binding Lectin and the Risk of Vascular Complications
      of Diabetes: Evidence from a Meta-Analysis.
AB  - BACKGROUND: Vascular inflammation associated with mannose-binding lectin (MBL)
      may be implicated in the pathogenesis of vascular complications in diabetes. The
      purpose of this study is to evaluate the association of MBL expression with
      vascular complications in diabetes. MATERIALS AND METHODS: Data from published
      case-control studies on MBL expression and vascular complications of diabetes
      were collected up to September 30, 2014. Medline, Embase, and Chinese National
      Knowledge Infrastructure (CNKI) were searched using the key words "MBL or mannose
      binding lectin or mannan-binding lectin," "diabetes or diabetic," and "vascular
      complication, vascular disease or angiopathy" to identify the articles published
      in English or Chinese. RESULTS: The combined odds ratio (OR) and 95% confidence
      interval (CI) for the cumulative rate of vascular complications in the cases of
      high-expression MBL versus that in cases of low-expression MBL were estimated
      using a fixed-effects model and a random-effects model. In total, 2,714 cases
      from 12 articles including 2,256 cases with high-expression MBL (>= 400 MUg/L)
      and 458 cases with low-expression MBL (< 400 MUg/L) were reviewed. The cumulative
      vascular complication rates were 52.9% (1,194/2,256) in the cases with high
      expression and 38.4% (176/458) in those with low expression. The combined ORs
      were 1.6, with a 95% CI ranging from 1.24 to 2.08, in the fixed-effects model and
      1.94, with a 95% CI from 1.00 to 3.76, in the random-effects model. CONCLUSIONS:
      High expression of MBL may be correlated with a significantly increased risk of
      vascular complications in diabetes. Thus MBL detection in diabetes is an
      effective and feasible method to predict vascular complications.

PMID- 25756787
TI  - Sleep and Recovery in Team Sport: Current Sleep-Related Issues Facing
      Professional Team-Sport Athletes.
AB  - While the effects of sleep loss on performance have previously been reviewed, the
      effects of disturbed sleep on recovery after exercise are less reported.
      Specifically, the interaction between sleep and physiological and psychological
      recovery in team-sport athletes is not well understood. Accordingly, the aim of
      the current review was to examine the current evidence on the potential role
      sleep may play in postexercise recovery, with a tailored focus on professional
      team-sport athletes. Recent studies show that team-sport athletes are at high
      risk of poor sleep during and after competition. Although limited published data
      are available, these athletes also appear particularly susceptible to reductions
      in both sleep quality and sleep duration after night competition and periods of
      heavy training. However, studies examining the relationship between sleep and
      recovery in such situations are lacking. Indeed, further observational sleep
      studies in team-sport athletes are required to confirm these concerns. Naps,
      sleep extension, and sleep-hygiene practices appear advantageous to performance;
      however, future proof-of-concept studies are now required to determine the
      efficacy of these interventions on postexercise recovery. Moreover, more research
      is required to understand how sleep interacts with numerous recovery responses in
      team-sport environments. This is pertinent given the regularity with which these
      teams encounter challenging scenarios during the course of a season. Therefore,
      this review examines the factors that compromise sleep during a season and after
      competition and discusses strategies that may help improve sleep in team-sport
      athletes. 

PMID- 25756789
TI  - Moving forward faster: the quest to apply evidence-based emergency practice
      guidelines in high school sports.

PMID- 25756788
TI  - Dibenzoylmethane exerts metabolic activity through regulation of AMP-activated
      protein kinase (AMPK)-mediated glucose uptake and adipogenesis pathways.
AB  - Dibenzoylmethane (DBM) has been shown to exert a variety of beneficial effects on
      human health. However, the mechanism of action is poorly understood. In this
      study, DBM increased phosphorylation of AMP-activated protein kinase (AMPK) and
      stimulated glucose uptake in a skeletal muscle cell line. Both knockdown of AMPK
      with siRNA and inhibition with AMPK inhibitor blocked DBM-induced glucose uptake.
      DBM increased the concentration of intracellular calcium and glucose uptake due
      to DBM was abolished by STO-609 (a calcium/calmodulin-dependent protein kinase
      inhibitor). DBM stimulated phosphorylation of p38 mitogen-activated protein
      kinase (p38 MAPK), which was blocked by pretreatment with compound C, an AMPK
      inhibitor. The expression of glucose transporter type 4 (GLUT4) was increased by
      DBM. The translocation of GLUT4 to the plasma membrane was also increased by DBM
      in AMPK dependently. In addition, DBM suppressed weight gain and prevented fat
      accumulation in the liver and abdomen in mice fed a high-fat diet. In pre
      adipocyte cells, DBM decreased the activity of acetyl-CoA carboxylase (ACC), the
      rate-limiting enzyme of fatty acid synthesis. Expression of the adipogenic gene,
      fatty acid synthase (FAS), was suppressed by DBM in an AMPK-dependent manner.
      These results showed that the beneficial metabolic effects of DBM might be due to
      regulation of glucose uptake via AMPK in skeletal muscle and inhibition of
      adipogenesis in pre-adipocytes. 

PMID- 25756790
TI  - Correlation of Shoulder and Elbow Kinetics With Ball Velocity in Collegiate
      Baseball Pitchers.
AB  - CONTEXT: Throwing a baseball is a dynamic and violent act that places large
      magnitudes of stress on the shoulder and elbow. Specific injuries at the elbow
      and glenohumeral joints have been linked to several kinetic variables throughout
      the throwing motion. However, very little research has directly examined the
      relationship between these kinetic variables and ball velocity. OBJECTIVE: To
      examine the correlation of peak ball velocity with elbow-valgus torque, shoulder
      external-rotation torque, and shoulder-distraction force in a group of collegiate
      baseball pitchers. DESIGN: Cross-sectional study. SETTING: Motion-analysis
      laboratory. PATIENTS OR OTHER PARTICIPANTS: Sixty-seven asymptomatic National
      Collegiate Athletic Association Division I baseball pitchers (age = 19.5 +/- 1.2
      years, height = 186.2 +/- 5.7 cm, mass = 86.7 +/- 7.0 kg; 48 right handed, 19
      left handed). MAIN OUTCOME MEASURE(S): We measured peak ball velocity using a
      radar gun and shoulder and elbow kinetics of the throwing arm using 8
      electronically synchronized, high-speed digital cameras. We placed 26 reflective
      markers on anatomical landmarks of each participant to track 3-dimensional
      coordinate data. The average data from the 3 highest-velocity fastballs thrown
      for strikes were used for data analysis. We calculated a Pearson correlation
      coefficient to determine the associations between ball velocity and peak elbow
      valgus torque, shoulder-distraction force, and shoulder external-rotation torque
      (P < .05). RESULTS: A weak positive correlation was found between ball velocity
      and shoulder-distraction force (r = 0.257; 95% confidence interval [CI] = 0.02,
      0.47; r(2) = 0.066; P = .018). However, no significant correlations were noted
      between ball velocity and elbow-valgus torque (r = 0.199; 95% CI = -0.043, 0.419;
      r(2) = 0.040; P = .053) or shoulder external-rotation torque (r = 0.097; 95% CI =
      -0.147, 0.329; r(2) = 0.009; P = .217). CONCLUSIONS: Although a weak positive
      correlation was present between ball velocity and shoulder-distraction force, no
      significant association was seen between ball velocity and elbow-valgus torque or
      shoulder external-rotation torque. Therefore, other factors, such as improper
      pitching mechanics, may contribute more to increases in joint kinetics than peak
      ball velocity.

PMID- 25756791
TI  - The ingenious structure of central rotor apparatus in VoV1; key for both complex
      disassembly and energy coupling between V1 and Vo.
AB  - Vacuolar type rotary H+-ATPases (VoV1) couple ATP synthesis/hydrolysis by V1 with
      proton translocation by Vo via rotation of a central rotor apparatus composed of
      the V1-DF rotor shaft, a socket-like Vo-C (eukaryotic Vo-d) and the hydrophobic
      rotor ring. Reconstitution experiments using subcomplexes revealed a weak binding
      affinity of V1-DF to Vo-C despite the fact that torque needs to be transmitted
      between V1-DF and Vo-C for the tight energy coupling between V1 and Vo. Mutation
      of a short helix at the tip of V1-DF caused intramolecular uncoupling of VoV1,
      suggesting that proper fitting of the short helix of V1-D into the socket of Vo-C
      is required for tight energy coupling between V1 and Vo. To account for the
      apparently contradictory properties of the interaction between V1-DF and Vo-C
      (weak binding affinity but strict requirement for torque transmission), we
      propose a model in which the relationship between V1-DF and Vo-C corresponds to
      that between a slotted screwdriver and a head of slotted screw. This model is
      consistent with our previous result in which the central rotor apparatus is not
      the major factor for the association of V1 with Vo (Kishikawa and Yokoyama, J
      Biol Chem. 2012 24597-24603). 

PMID- 25756792
TI  - Functional analysis helps to define KCNC3 mutational spectrum in Dutch ataxia
      cases.
AB  - Spinocerebellar ataxia type 13 (SCA13) is an autosomal dominantly inherited
      neurodegenerative disorder of the cerebellum caused by mutations in the voltage
      gated potassium channel KCNC3. To identify novel pathogenic SCA13 mutations in
      KCNC3 and to gain insights into the disease prevalence in the Netherlands, we
      sequenced the entire coding region of KCNC3 in 848 Dutch cerebellar ataxia
      patients with familial or sporadic origin. We evaluated the pathogenicity of the
      identified variants by co-segregation analysis and in silico prediction followed
      by biochemical and electrophysiological studies. We identified 19 variants in
      KCNC3 including 2 non-coding, 11 missense and 6 synonymous variants. Two missense
      variants did not co-segregate with the disease and were excluded as potentially
      disease-causing mutations. We also identified the previously reported p.R420H and
      p.R423H mutations in our cohort. Of the remaining 7 missense variants, functional
      analysis revealed that 2 missense variants shifted Kv3.3 channel activation to
      more negative voltages. These variations were associated with early disease onset
      and mild intellectual disability. Additionally, one other missense variant
      shifted channel activation to more positive voltages and was associated with
      spastic ataxic gait. Whereas, the remaining missense variants did not change any
      of the channel characteristics. Of these three functional variants, only one
      variant was in silico predicted to be damaging and segregated with disease. The
      other two variants were in silico predicted to be benign and co-segregation
      analysis was not optimal or could only be partially confirmed. Therefore, we
      conclude that we have identified at least one novel pathogenic mutation in KCNC3
      that cause SCA13 and two additionally potential SCA13 mutations. This leads to an
      estimate of SCA13 prevalence in the Netherlands to be between 0.6% and 1.3%. 

PMID- 25756793
TI  - Increased visceral adipose tissue as a potential risk factor in patients with
      embolic stroke of undetermined source (ESUS).
AB  - PURPOSE: The etiology of an ischemic stroke remains undetermined in 20-35% of
      cases and many patients do not have any of the conventional risk factors.
      Increased visceral adipose tissue (VAT) is a suggested new risk factor for both
      carotid artery atherosclerosis (CAA) and atrial fibrillation (AF), but its role
      in the remaining stroke population is unknown. We assessed the amount of VAT in
      patients with embolic stroke of undetermined source (ESUS) after excluding major
      risk cardioembolic sources, occlusive atherosclerosis, and lacunar stroke.
      METHODS: Altogether 58 patients (mean age 57.7 +/- 10.2 years, 44 men) with
      ischemic stroke of unknown etiology but without CAA, known AF or small vessel
      disease underwent computed tomography angiography and assessment of VAT. For
      comparison VAT values from three different reference populations were used.
      Conventional risk factors (smoking, hypertension, diabetes, increased total and
      LDL-cholesterol, decreased HDL-cholesterol) were also registered. RESULTS: Mean
      VAT area was significantly higher in stroke patients (205 +/- 103 cm2 for men and
      168 +/- 99 cm2 for women) compared to all reference populations (P < 0.01). 50%
      of male and 57% of female patients had an increased VAT area. In male patients,
      VAT was significantly higher despite similar body mass index (BMI). Increased VAT
      was more common than any of the conventional risk factors. CONCLUSION: Increased
      VAT was found in over half of our patients with ESUS suggesting it may have a
      role in the pathogenesis of thromboembolism in this selected group of patients.

PMID- 25756794
TI  - Catecholaminergic and cholinergic systems of mouse brain are modulated by LMN
      diet, rich in theobromine, polyphenols and polyunsaturated fatty acids.
AB  - The possible modulatory effect of the functional LMN diet, rich in theobromine,
      polyphenols and polyunsaturated fatty acids, on the catecholaminergic and
      cholinergic neurotransmission, affecting cognition decline during aging has been
      studied. 129S1/SvlmJ mice were fed for 10, 20, 30 and 40 days with either LMN or
      control diets. The enzymes involved in catecholaminergic and cholinergic
      metabolism were determined by both immunohistological and western blot analyses.
      Noradrenalin, dopamine and other metabolites were quantified by HPLC analysis.
      Theobromine, present in cocoa, the main LMN diet component, was analysed in
      parallel using SH-SY5Y and PC12 cell lines. An enhanced modulatory effect on both
      cholinergic and catecholaminergic transmissions was observed on 20 day fed mice.
      Similar effect was observed with theobromine, besides its antioxidant capacity
      inducing SOD-1 and GPx expression. The enhancing effect of the LMN diet and
      theobromine on the levels of acetylcholine-related enzymes, dopamine and
      specially noradrenalin confirms the beneficial role of this diet on the
      "cognitive reserve" and hence a possible reducing effect on cognitive decline
      underlying aging and Alzheimer's disease. 

PMID- 25756795
TI  - Positive pressure therapy for Meniere's disease or syndrome.
AB  - BACKGROUND: Meniere's disease is an incapacitating disease in which recurrent
      attacks of vertigo are accompanied by hearing loss, tinnitus and/or aural
      fullness, all of which are discontinuous and variable in intensity. A number of
      different therapies have been identified for patients with this disease, ranging
      from dietary measures (e.g. a low-salt diet) and medication (e.g. betahistine
      (Serc(r)), diuretics) to extensive surgery (e.g. endolymphatic sac surgery). The
      Meniett(r) low-pressure pulse generator (Medtronic ENT, 1999) is a device that is
      designed to generate a computer-controlled sequence of low-pressure (micro
      pressure) pulses, which are thought to be transmitted to the vestibular system of
      the inner ear. The pressure pulse passes via a tympanostomy tube (grommet) to the
      middle ear, and hence to the inner ear via the round and/or oval window. The
      hypothesis is that these low-pressure pulses reduce endolymphatic hydrops.
      OBJECTIVES: To assess the effects of positive pressure therapy (e.g. the Meniett
      device) on the symptoms of Meniere's disease or syndrome. SEARCH METHODS: We
      searched the Cochrane Ear, Nose and Throat Disorders Group Trials Register; the
      Cochrane Central Register of Controlled Trials (CENTRAL); PubMed; EMBASE; CINAHL;
      Web of Science; Cambridge Scientific Abstracts; ICTRP and additional sources for
      published and unpublished trials. The date of the search was 6 June 2014.
      SELECTION CRITERIA: Randomised controlled trials (RCTs) comparing positive
      pressure therapy (using the Meniett or a similar device) with placebo in patients
      with Meniere's disease. The primary outcome was control of vertigo; secondary
      outcomes were loss or gain of hearing, severity of tinnitus, perception of aural
      fullness, functional level, complications or adverse effects, and sick days. DATA
      COLLECTION AND ANALYSIS: Two authors independently selected studies, assessed
      risk of bias and extracted data. We contacted authors for additional data. Where
      possible, we pooled study results using a fixed-effect, mean difference (MD) meta
      analysis and tested for statistical heterogeneity using both the Chi2 test and I2
      statistic. This was only possible for the secondary outcomes loss or gain of
      hearing and sick days. We presented results using forest plots with 95%
      confidence intervals (Cl). MAIN RESULTS: We included five randomised clinical
      trials with 265 participants. All trials were prospective, double-blind, placebo
      controlled randomised controlled trials on the effects of positive pressure
      therapy on vertigo complaints in Meniere's disease. Overall, the risk of bias
      varied: three out of five studies were at low risk, one was at unclear risk and
      one was at high risk of bias. Control of vertigo For the primary outcome, control
      of vertigo, it was not possible to pool data due to heterogeneity in the
      measurement of the outcome measures. In most studies, no significant difference
      was found between the positive pressure therapy group and the placebo group in
      vertigo scores or vertigo days. Only one study, at low risk of bias, showed a
      significant difference in one measure of vertigo control in favour of positive
      pressure therapy. In this study, the mean visual analogue scale (VAS) score for
      vertigo after eight weeks of treatment was 25.5 in the positive pressure therapy
      group and 46.6 in the placebo group (mean difference (MD) -21.10, 95% CI -35.47
      to -6.73; scale not stated - presumed to be 0 to 100). Secondary outcomes For the
      secondary outcomes, we carried out two pooled analyses. We found statistically
      significant results for loss or gain of hearing . Hearing was 7.38 decibels
      better in the placebo group compared to the positive pressure therapy group (MD)
      (95% CI 2.51 to 12.25; two studies, 123 participants). The severity of tinnitus
      and perception of aural fullness were either not measured or inadequate data were
      provided in the included studies. For the secondary outcome functional level , it
      was not possible to perform a pooled analysis. One included study showed less
      functional impairment in the positive pressure group than the placebo group (AAO
      HNS criteria, one- to six-point scale: MD -1.10, 95% CI -1.81 to -0.39, 40
      participants); another study did not show any significant results. In addition to
      the predefined secondary outcome measures, we included sick days as an additional
      outcome measure, as two studies used this outcome measure and it is a
      complementary measurement of impairment due to Meniere's disease. We did not find
      a statistically significant difference in sick days. No complications or adverse
      effects were noted by any study. AUTHORS' CONCLUSIONS: There is no evidence, from
      five included studies, to show that positive pressure therapy is effective for
      the symptoms of Meniere's disease. There is some moderate quality evidence, from
      two studies, that hearing levels are worse in patients who use this therapy. The
      positive pressure therapy device itself is minimally invasive. However, in order
      to use it, a tympanostomy tube (grommet) needs to be inserted, with the
      associated risks. These include the risks of anaesthesia, the general risks of
      any surgery and the specific risks of otorrhoea and tympanosclerosis associated
      with the insertion of a tympanostomy tube. Notwithstanding these comments, no
      complications or adverse effects were noted in any of the included studies.

PMID- 25756796
TI  - Standard (head-down tilt) versus modified (without head-down tilt) postural
      drainage in infants and young children with cystic fibrosis.
AB  - BACKGROUND: Postural drainage is used primarily in infants with cystic fibrosis
      from diagnosis up to the moment when they are mature enough to actively
      participate in self-administered treatments. However, there is a risk of
      gastroesophageal reflux associated with this technique. OBJECTIVES: To compare
      the effects of standard postural drainage (greater (30 degrees  to 45 degrees 
      head-down tilt) and lesser (15 degrees  to 20 degrees  head-down tilt)) with
      modified postural drainage (greater (30o head-up tilt) or lesser (15o to 20o head
      up tilt)) with regard to gastroesophageal reflux in infants and young children up
      to six years old with cystic fibrosis in terms of safety and efficacy. SEARCH
      METHODS: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's
      Cystic Fibrosis Trials Register. We also searched the reference lists of relevant
      articles and reviews. Additional searches were conducted on ClinicalTrials.gov
      and on the WHO International Clinical Trials Registry Platform for any planned,
      ongoing and unpublished studies.The date of the most recent literature searches:
      20 January 2015. SELECTION CRITERIA: We included randomised controlled studies
      that compared two postural drainage regimens (standard and modified postural
      drainage) with regard to gastroesophageal reflux in infants and young children
      (up to and including six years old) with cystic fibrosis. DATA COLLECTION AND
      ANALYSIS: Two review authors independently selected the studies to be included in
      the review, assessed their risk of bias and extracted data. MAIN RESULTS: Two
      studies, including 40 participants, were eligible for inclusion in the review.
      The studies were different in terms of the age of participants, the angle of
      tilt, the reported outcomes, the number of sessions and the study duration. The
      following outcomes were measured: appearance or exacerbation of gastroesophageal
      reflux episodes; percentage of peripheral oxygen saturation; number of
      exacerbations of upper respiratory tract symptoms; number of days on antibiotics
      for acute exacerbations; chest X-ray scores; and pulmonary function tests. One
      study reported that postural drainage with a 20 degrees  head-down position did
      not appear to exacerbate gastroesophageal reflux. However, the majority of the
      reflux episodes reached the upper oesophagus. The second included study reported
      that modified postural drainage (30o head-up tilt) was associated with fewer
      number of gastroesophageal reflux episodes and fewer respiratory complications
      than standard postural drainage (30o head-down tilt). The included studies had an
      overall low risk of bias. Data were not able to be pooled by meta-analysis due to
      differences in the statistical presentation of the data. AUTHORS' CONCLUSIONS:
      The available evidence regarding the comparison between the two regimens of
      postural drainage is still weak due to the small number of included studies, the
      small number of participants assessed, the inability to perform any meta-analyses
      and some methodological issues with the studies. However, it may be inferred that
      the use of a postural regimen with a 30 degrees  head-up tilt is associated with
      a lower number of gastroesophageal reflux episodes and fewer respiratory
      complications in the long term. The 20o head-down postural drainage position was
      not found to be significantly different from the 20o head-up tilt modified
      position. Nevertheless, the fact that the majority of reflux episodes reached the
      upper oesophagus should make physiotherapists carefully consider their treatment
      strategy.

PMID- 25756797
TI  - Geographical and Temporal Correlations in the Incidence of Lyme Disease, RMSF,
      Ehrlichiosis, and Coccidioidomycosis with Search Data.

PMID- 25756798
TI  - Fidgetin-Like 2: A Microtubule-Based Regulator of Wound Healing.
AB  - Wound healing is a complex process driven largely by the migration of a variety
      of distinct cell types from the wound margin into the wound zone. In this study,
      we identify the previously uncharacterized microtubule-severing enzyme, Fidgetin
      like 2 (FL2), as a fundamental regulator of cell migration that can be targeted
      in vivo using nanoparticle-encapsulated small interfering RNA (siRNA) to promote
      wound closure and regeneration. In vitro, depletion of FL2 from mammalian tissue
      culture cells results in a more than twofold increase in the rate of cell
      movement, in part due to a significant increase in directional motility.
      Immunofluorescence analyses indicate that FL2 normally localizes to the cell
      edge, importantly to the leading edge of polarized cells, where it regulates the
      organization and dynamics of the microtubule cytoskeleton. To clinically
      translate these findings, we utilized a nanoparticle-based siRNA delivery
      platform to locally deplete FL2 in both murine full-thickness excisional and burn
      wounds. Topical application of FL2 siRNA nanoparticles to either wound type
      results in a significant enhancement in the rate and quality of wound closure
      both clinically and histologically relative to controls. Taken together, these
      results identify FL2 as a promising therapeutic target to promote the
      regeneration and repair of cutaneous wounds. 

PMID- 25756800
TI  - A genome-wide identification and classification of basic helix-loop-helix genes
      in the jewel wasp, Nasonia vitripennis (Hymenoptera: Pteromalidae).
AB  - Basic helix-loop-helix (bHLH) proteins are highly conserved DNA-binding
      transcription factors of a large superfamily. Animal bHLH proteins play important
      regulatory roles in various developmental processes such as neurogenesis,
      myogenesis, heart development, and hematopoiesis. The jewel wasp (Nasonia
      vitripennis) is a good model organism of hymenoptera insects for studies of
      developmental and evolutionary genetics. In this study, we identified 48 bHLH
      genes in the genome of N. vitripennis. According to phylogenetic analysis, based
      on N. vitripennis bHLH (NvbHLH) motif sequences and structural domain
      distribution in their full-length protein sequences, the identified NvbHLH genes
      were classified into 36 bHLH families with 19, 12, 9, 1, 6, and 1 member(s) in
      groups A, B, C, D, E, and F, respectively. Our classification to the identified
      NvbHLH family members confirms GenBank annotations for 21 of the 48 NvbHLH
      proteins and provides useful information for further characterization and
      annotation of the remaining 27 NvbHLH proteins. Compared to other insect species,
      N. vitripennis has the lowest number of bHLH family members. No NvbHLH members
      have been found in the families Net, MyoRa, and PTFa, while all other insect
      species have at least one member in each of the families. These data constitute a
      solid basis for further investigations into the functions of bHLH proteins in
      developmental regulation of N. vitripennis. 

PMID- 25756799
TI  - Melanoma Cell Galectin-1 Ligands Functionally Correlate with Malignant Potential.
AB  - Galectin-1 (Gal-1)-binding to Gal-1 ligands on immune and endothelial cells can
      influence melanoma development through dampening antitumor immune responses and
      promoting angiogenesis. However, whether Gal-1 ligands are functionally expressed
      on melanoma cells to help control intrinsic malignant features remains poorly
      understood. Here, we analyzed expression, identity, and function of Gal-1 ligands
      in melanoma progression. Immunofluorescent analysis of benign and malignant human
      melanocytic neoplasms revealed that Gal-1 ligands were abundant in severely
      dysplastic nevi, as well as in primary and metastatic melanomas. Biochemical
      assessments indicated that melanoma cell adhesion molecule (MCAM) was a major Gal
      1 ligand on melanoma cells that was largely dependent on its N-glycans. Other
      melanoma cell Gal-1 ligand activity conferred by O-glycans was negatively
      regulated by alpha2,6 sialyltransferase ST6GalNAc2. In Gal-1-deficient mice, MCAM
      silenced (MCAM(KD)) or ST6GalNAc2-overexpressing (ST6(O/E)) melanoma cells
      exhibited slower growth rates, underscoring a key role for melanoma cell Gal-1
      ligands and host Gal-1 in melanoma growth. Further analysis of MCAM(KD) or
      ST6(O/E) melanoma cells in cell migration assays indicated that Gal-1 ligand
      dependent melanoma cell migration was severely inhibited. These findings provide
      a refined perspective on Gal-1/melanoma cell Gal-1 ligand interactions as
      contributors to melanoma malignancy. 

PMID- 25756801
TI  - Extracorporeal life support and multiorgan donation in a severe polytrauma
      patient: A case report.
AB  - INTRODUCTION: Organ availability represents a key factor in transplants due to an
      almost universal shortage of deceased donors. PRESENTATION OF CASE: We present
      the case of a 41-year-old patients with severe polytrauma, where extracorporeal
      life support (ECLS) allowed brain death (BD) declaration and multiorgan retrieval
      and transplantation. DISCUSSION: Organ procurement is of utmost importance for
      transplant procedures. The presented case could rise ethical doubts as ECLS could
      be viewed as a tool for organ preservation instead of patient support.
      Nonetheless, it is obvious how organ preservation represents the necessary
      condition for patient preservation. CONCLUSION: Besides it' role in non heart
      beating donors, ECLS is emerging as an adjunctive tool for brain dead donors
      management when standard treatment fails, potentially allowing a substantial
      increase in organ availability.

PMID- 25756802
TI  - Enhancement of beta-secretase inhibition and antioxidant activities of tempeh, a
      fermented soybean cake through enrichment of bioactive aglycones.
AB  - CONTEXT: Soybean and its fermented products are the most common source of
      isoflavones in human food. OBJECTIVE: The present study quantifies the major
      glycosides and aglycones in soybean and its fermented product tempeh isoflavone
      extracts. The comparision of antioxidant effects and BACE1 inhibitory activity
      between the isoflavones of soybean and tempeh were also established. MATERIALS
      AND METHODS: The major isoflavones such as daidzein and genistein (aglycones),
      and their sugar conjugates (glycosides) daidzin and genistin in soybean and
      tempeh isoflavones were quantified using HPLC analysis. Comparative studies on
      BACE 1 (beta-site amyloid precursor protein cleaving enzyme 1 or beta-secretase
      1) inhibition and free-radical scavenging activities (diphenyl-1-picrylhydrazyl
      (DPPH) and ferrous ion chelating ability) were conducted. RESULTS: The amount of
      actives (mg/100 g) in soybean isoflavone compared with tempeh isoflavone is as
      follows: daidzein 16.72 mg/100 g versus 38.91 mg/100 g, genistein 11.10 mg/100 g
      versus 24.03 mg/100 g, daidzin 6.16 mg/100 g versus 0.69 mg/100 g, and genistin
      24.61 mg/100 g versus 6.57 mg/100 g. The IC50 values of soybean and tempeh
      isoflavones against BACE1 were 10.87 and 5.47 mg/ml, respectively. The tempeh
      isoflavone had a more potent DPPH free-radical scavenging activity (IC50 = 2.67
      mg/ml) than the soybean isoflavone (IC50 = 10 mg/ml). The ferrous ion chelating
      ability of the isoflavones was practically similar (IC50 = 10.40 mg/ml, soybean
      and 11.13 mg/ml, tempeh). DISCUSSION AND CONCLUSION: The present study indicates
      that tempeh is a healthy supplement to alleviate oxidative stress through the
      enrichment of aglycones.

PMID- 25756803
TI  - Use of Dual-Source Computed Tomography to Evaluate Renal Cortical Perfusion in
      Patients With Essential Hypertension Without Diabetes: Preliminary Results.
AB  - OBJECTIVES: To assess renal cortical perfusion parameter changes using computed
      tomography (CT) renal perfusion examination in patients with essential
      hypertension (EH), especially those with EH-related target organ damage (TOD),
      and to correlate renal perfusion parameters with clinical and laboratory data.
      METHODS: Consecutive patients with EH (without exclusion criteria) and healthy
      controls underwent 128-slice dual-source CT perfusion imaging. Quantitative
      perfusion analysis of renal cortex parameters [blood flow (BF), blood volume,
      time to peak, and mean transit time] was performed. RESULTS: Ninety-one
      participants (60 patients with EH, 31 healthy controls) underwent renal perfusion
      CT imaging, and 84 participants (92.3%) were eligible for perfusion analysis. The
      BF values were lower in patients with EH than that in controls. Blood flow was
      correlated with age (P < 0.01), duration of hypertension (P < 0.01), estimated
      glomerular filtration rate (eGFR; P < 0.01), pulse pressure (P < 0.05), and body
      mass index (BMI; P < 0.05). Duration of hypertension, eGFR, and BMI were
      independently associated with BF. No parameter differed between control subjects
      and those with EH but not. Blood flow was lower in patients with TOD than in
      control subjects (P < 0.01), but no other parameter differed. Blood flow was
      lower (P < 0.01) and mean transit time and time to peak were higher (P < 0.05) in
      the TOD than that in the non-TOD group. CONCLUSIONS: Essential hypertension,
      especially EH-related TOD, alters renal cortical perfusion parameters, especially
      BF. Four-dimensional spiral CT renal perfusion examination showed that duration
      of hypertension, eGFR, and BMI were independently associated with decreased BF.

PMID- 25756804
TI  - Clot Through the Heart: Paradoxical Embolism With Thrombus-in-Transit at
      Multidetector Computed Tomography.
AB  - We present the case of a 67-year-old man with concomitant stroke and pulmonary
      embolism 1 day after radiofrequency catheter ablation for refractory atrial
      tachycardia. A chest computed tomographic angiogram revealed "thrombus-in
      transit" across a patent foramen ovale, confirming the diagnosis of paradoxical
      embolism. Paradoxical embolism is a rare definitive diagnosis. Our case is a key
      demonstration of the even rarer instance where such a diagnosis is confirmed at
      multidetector computed tomography. 

PMID- 25756805
TI  - Early-life lead exposure recapitulates the selective loss of parvalbumin-positive
      GABAergic interneurons and subcortical dopamine system hyperactivity present in
      schizophrenia.
AB  - Environmental factors have been associated with psychiatric disorders and recent
      epidemiological studies suggest an association between prenatal lead (Pb(2+))
      exposure and schizophrenia (SZ). Pb(2+) is a potent antagonist of the N-methyl-D
      aspartate receptor (NMDAR) and converging evidence indicates that NMDAR
      hypofunction has a key role in the pathophysiology of SZ. The glutamatergic
      hypothesis of SZ posits that NMDAR hypofunction results in the loss of
      parvalbumin (PV)-positive GABAergic interneurons (PVGI) in the brain. Loss of
      PVGI inhibitory control to pyramidal cells alters the excitatory drive to
      midbrain dopamine neurons increasing subcortical dopaminergic activity. We
      hypothesized that if Pb(2+) exposure in early life is an environmental risk
      factor for SZ, it should recapitulate the loss of PVGI and reproduce subcortical
      dopaminergic hyperactivity. We report that on postnatal day 50 (PN50),
      adolescence rats chronically exposed to Pb(2+) from gestation through adolescence
      exhibit loss of PVGI in SZ-relevant brain regions. PV and glutamic acid
      decarboxylase 67 kDa (GAD67) protein were significantly decreased in Pb(2+)
      exposed rats with no apparent change in calretinin or calbindin protein levels
      suggesting a selective effect on the PV phenotype of GABAergic interneurons. We
      also show that Pb(2+) animals exhibit a heightened locomotor response to cocaine
      and express significantly higher levels of dopamine metabolites and D2-dopamine
      receptors relative to controls indicative of subcortical dopaminergic
      hyperactivity. Our results show that developmental Pb(2+) exposure reproduces
      specific neuropathology and functional dopamine system changes present in SZ. We
      propose that exposure to environmental toxins that produce NMDAR hypofunction
      during critical periods of brain development may contribute significantly to the
      etiology of mental disorders. 

PMID- 25756806
TI  - Fibroblasts from patients with major depressive disorder show distinct
      transcriptional response to metabolic stressors.
AB  - Major depressive disorder (MDD) is increasingly viewed as interplay of
      environmental stressors and genetic predisposition, and recent data suggest that
      the disease affects not only the brain, but the entire body. As a result, we
      aimed at determining whether patients with major depression have aberrant
      molecular responses to stress in peripheral tissues. We examined the effects of
      two metabolic stressors, galactose (GAL) or reduced lipids (RL), on the
      transcriptome and miRNome of human fibroblasts from 16 pairs of patients with MDD
      and matched healthy controls (CNTR). Our results demonstrate that both MDD and
      CNTR fibroblasts had a robust molecular response to GAL and RL challenges. Most
      importantly, a significant part (messenger RNAs (mRNAs): 26-33%; microRNAs
      (miRNAs): 81-90%) of the molecular response was only observed in MDD, but not in
      CNTR fibroblasts. The applied metabolic challenges uncovered mRNA and miRNA
      signatures, identifying responses to each stressor characteristic for the MDD
      fibroblasts. The distinct responses of MDD fibroblasts to GAL and RL revealed an
      aberrant engagement of molecular pathways, such as apoptosis, regulation of cell
      cycle, cell migration, metabolic control and energy production. In conclusion,
      the metabolic challenges evoked by GAL or RL in dermal fibroblasts exposed
      adaptive dysfunctions on mRNA and miRNA levels that are characteristic for MDD.
      This finding underscores the need to challenge biological systems to bring out
      disease-specific deficits, which otherwise might remain hidden under resting
      conditions.

PMID- 25756807
TI  - Mitochondrial genetic variants identified to be associated with posttraumatic
      stress disorder.
AB  - Despite the fact that mitochondrial dysfunctions are increasingly recognized as
      key components in stress-related mental disorders, very little is known about the
      association between posttraumatic stress disorder (PTSD) and mitochondrial
      variants. To identify susceptibility mitochondrial genes for PTSD, we analyzed a
      total number of 978 mitochondrial single-nucleotide polymorphisms (mtSNPs) in a
      sample of 1238 individuals participating in the KORA (Cooperative Health Research
      in the Region of Augsburg) study. Participants were classified with 'no PTSD',
      'partial PTSD' or 'full PTSD' by applying the Posttraumatic Diagnostic Scale and
      the Impact of Event Scale. To assess PTSD-mtSNP association while taking
      heteroplasmy into account, we used the raw signal intensity values measured on
      the microarray and applied linear regression. Significant associations were
      obtained between full versus no PTSD and two mtSNPs; mt8414C->T (beta=-0.954+/
      0.06, Padjusted=0.037) located in adenosine triphosphate (ATP) synthase subunit 8
      (MT-ATP8) and mt12501G->A (beta=-1.782+/-0.40, Padjusted=0.015) located in the
      NADH dehydrogenase subunits 5 (MT-ND5). Heteroplasmy for the two variants towards
      a larger number of the respective minor alleles increases the risk of having
      PTSD. NADH dehydrogenase and ATP synthase are both linked to the regulation of
      reactive oxygen species. Our results highlight the important role of the
      mitochondrial genome among the factors that contribute to the risk of PTSD.
      Mitochondrial genetic variants may be more important than has previously been
      assumed, leading to further insights regarding effects of existing medications,
      or even to the development of innovative treatments. As this is the first
      mitochondrial genome-wide association study for PTSDs, further analyses are
      needed to follow up on the present findings.

PMID- 25756809
TI  - Oxidative stress induces mitochondrial dysfunction in a subset of autistic
      lymphoblastoid cell lines.

PMID- 25756810
TI  - Gut flora, diet and intestinal metabolism on cardiovascular risk.

PMID- 25756808
TI  - Lack of parvalbumin in mice leads to behavioral deficits relevant to all human
      autism core symptoms and related neural morphofunctional abnormalities.
AB  - Gene mutations and gene copy number variants are associated with autism spectrum
      disorders (ASDs). Affected gene products are often part of signaling networks
      implicated in synapse formation and/or function leading to alterations in the
      excitation/inhibition (E/I) balance. Although the network of parvalbumin (PV)
      expressing interneurons has gained particular attention in ASD, little is known
      on PV's putative role with respect to ASD. Genetic mouse models represent
      powerful translational tools for studying the role of genetic and neurobiological
      factors underlying ASD. Here, we report that PV knockout mice (PV(-/-)) display
      behavioral phenotypes with relevance to all three core symptoms present in human
      ASD patients: abnormal reciprocal social interactions, impairments in
      communication and repetitive and stereotyped patterns of behavior. PV-depleted
      mice also showed several signs of ASD-associated comorbidities, such as reduced
      pain sensitivity and startle responses yet increased seizure susceptibility,
      whereas no evidence for behavioral phenotypes with relevance to anxiety,
      depression and schizophrenia was obtained. Reduced social interactions and
      communication were also observed in heterozygous (PV(+/-)) mice characterized by
      lower PV expression levels, indicating that merely a decrease in PV levels might
      be sufficient to elicit core ASD-like deficits. Structural magnetic resonance
      imaging measurements in PV(-/-) and PV(+/-) mice further revealed ASD-associated
      developmental neuroanatomical changes, including transient cortical hypertrophy
      and cerebellar hypoplasia. Electrophysiological experiments finally demonstrated
      that the E/I balance in these mice is altered by modification of both inhibitory
      and excitatory synaptic transmission. On the basis of the reported changes in PV
      expression patterns in several, mostly genetic rodent models of ASD, we propose
      that in these models downregulation of PV might represent one of the points of
      convergence, thus providing a common link between apparently unrelated ASD
      associated synapse structure/function phenotypes. 

PMID- 25756811
TI  - HDL - Hope Dies Last?

PMID- 25756812
TI  - Atherosclerosis: cell biology and lipoproteins.

PMID- 25756817
TI  - Preface.

PMID- 25756814
TI  - Efficacy of Postoperative Antimicrobial Use for Clean Orthopedic Implant Surgery
      in Dogs: A Prospective Randomized Study in 100 Consecutive Cases.
AB  - OBJECTIVES: To investigate whether administration of postoperative oral
      antimicrobial drugs has a beneficial effect on preventing surgical site
      infections (SSI) in clean orthopedic surgery involving stainless steel plating
      systems. STUDY DESIGN: Randomized prospective clinical study. ANIMALS: Dogs (n =
      97). METHODS: One hundred consecutive cases (97 dogs) that had clean orthopedic
      surgery requiring stainless steel plate fixation were randomly assigned using a
      random number generator to either YES group (administration of postoperative oral
      antimicrobials) or NO group (no administration of postoperative oral
      antimicrobials). Dogs in YES group were administered oral cefalexin or
      potentiated amoxicillin for 7 days, whereas dogs in NO group were discharged
      without oral antibiotics. Minimum follow-up was 12 months. Multivariable logistic
      regression was used to determine risk factors for SSI. RESULTS: Overall
      postoperative infection rate was 12.9%. Infection occurred in 2 cases (4.3%)
      administered postoperative oral antimicrobials and in 10 cases (21.3%) not
      administered postoperative antimicrobials. Total anesthetic time and use of oral
      antimicrobials were the only significant factors associated with SSI. Use of
      postoperative antimicrobials was associated with a significant reduction in the
      risk of infection by ~84% and risk of infection was increased by ~2% for each
      minute increase in anesthesia time. CONCLUSIONS: Administration of oral
      postoperative antimicrobials had a protective effect against development of SSI
      in clean orthopedic implant surgery.

PMID- 25756818
TI  - Editorial: synthesis and CNS activity of medicinal important heterocyclic
      compounds.

PMID- 25756819
TI  - Pyrimidine derivatives as potential agents acting on central nervous system.
AB  - Pyrimidine and its derivatives are present in many of the bioactive aromatic
      compounds that are of wide interest because of their diverse biological and
      clinical applications. The utility of pyrimidines as synthon for various
      biologically active compounds has given impetus to these studies. The review
      article aims to review the work reported on pharmacological activities of central
      nervous system (CNS) such as anticonvulsant and antidepressant, which created
      interest among researchers to synthesize variety of pyrimidine and their
      derivatives. The present study shows, objective of the work can be summarized as
      pyrimidine derivative constitute an important class of compounds for new drug
      development. These observations have been given novel idea for the development of
      new pyrimidine derivative that possess varied biological activities. This article
      aims to review the recent works on pyrimidine moiety together with the biological
      potential during the past year. 

PMID- 25756820
TI  - Plating of femoral neck fractures: when and how?
AB  - Intracapsular femoral neck fractures are common in the elderly population after a
      simple fall. However, femoral neck fractures in the physiologically young are
      less common. Regardless, femoral neck fractures can be a source of significant
      morbidity and mortality if not treated correctly. Multiple management strategies
      have been described. The decision for the ideal treatment involves careful
      consideration of the patient's age, activity, and medical comorbidities. Plating
      techniques of femoral neck fractures continue to evolve. The authors describe the
      current indications and plating options for the treatment of femoral neck
      fractures. 

PMID- 25756821
TI  - Nailing intertrochanteric hip fractures: short versus long; locked versus
      nonlocked.
AB  - A large number of implants have been developed for intramedullary fixation of
      intertrochanteric fractures. This article attempts to summarize the contemporary
      understanding of the existing biomechanical and clinical evidence on
      intramedullary nailing of intertrochanteric fractures, as to whether they should
      be short or long nails, and the use or not of distal locking screws. Difficulties
      on the translation of biomechanical findings to the clinical setting, as well as
      the pressing demand for standardization of the indications and the use of
      different modes of cephalomedullary nailing, should direct orthopaedic trauma
      research toward focused, well-designed clinical studies. LEVEL OF EVIDENCE: Level
      V-expert opinion.

PMID- 25756822
TI  - Considerations with failed intertrochanteric and subtrochanteric femur fractures:
      how to treat, revise, and replace.
AB  - With the increasing number of intertrochanteric and subtrochanteric femur
      fractures, there will be an increasing need for surgical intervention. As a
      result, there will be an increasing number of failures and the need for revision
      surgery. The following outlines some of the pitfalls related to these complex
      fractures and options for revision surgery. 

PMID- 25756823
TI  - Nailing proximal femur fractures: how to choose starting point and proximal screw
      configuration.
AB  - Fractures of the proximal femur can be a challenging treatment dilemma for the
      orthopaedic surgeon. Complex mechanical forces and anatomic variables in this
      region combine to make treatment of these injuries difficult and can often result
      in serious complications. The decision to treat this fracture with an
      intramedullary device requires the surgeon evaluate many variables in the context
      of the specific fracture pattern. These include the choice of implant, starting
      portal location, and positioning of the patient. Assessment of the fracture
      pattern and its 3 dimensional orientation is usually accomplished with the aid of
      advanced imaging. The patient's physiological status, body habitus and bone
      quality must also be incorporated into the treatment algorithm. We review these
      issues and how they factor into the decision making process in order to develop a
      successful operative plan for these injuries. We will review the starting portal
      selection, reduction and insertion techniques and examine options for proximal
      locking screw configurations. 

PMID- 25756824
TI  - Reducing subtrochanteric femur fractures: tips and tricks, do's and don'ts.
AB  - Treatment of subtrochanteric fracture remains a challenge, but evolution of
      strategy has allowed for reliable results with low complications. Although
      several fixation options exist, reamed, antegrade intramedullary nailing (IMN)
      has evolved as the standard of care. Cognizant effort to achieve anatomic
      reduction before IMN passage allows for desired outcomes. Several reduction
      techniques can be used to overcome the deforming forces present in the proximal
      femur to allow for proper IMN placement. The purpose of this article is to review
      the tips, tricks, and pitfalls to avoid in the treatment of subtrochanteric femur
      fractures with IMN. 

PMID- 25756825
TI  - What makes an intertrochanteric fracture unstable in 2015? Does the lateral wall
      play a role in the decision matrix?
AB  - Intertrochanteric (IT) fractures pose a tremendous burden to the healthcare
      system. Although consistently good results are obtained while treating stable IT
      fractures, treatment failure rates with unstable fractures are much higher, and
      hence, it is imperative to identify unstable patterns. Presently, the
      conventionally classified unstable configurations (fracture with posteromedial
      comminution, reverse oblique, IT with subtrochanteric extension) and the recently
      added fracture patterns (IT fractures with avulsed greater trochanter and lateral
      wall breach) qualify as unstable IT fractures; however, the list is certainly not
      exhaustive. Disruption of lateral wall converts an IT fracture into a reverse
      oblique fracture equivalent and should be given a strong consideration in the
      decision matrix. 

PMID- 25756826
TI  - Highly sensitive and specific detection of E. coli by a SERS nanobiosensor chip
      utilizing metallic nanosculptured thin films.
AB  - A nanobiosensor chip, utilizing surface enhanced Raman spectroscopy (SERS) on
      nanosculptured thin films (nSTFs) of silver, was shown to detect Escherichia coli
      (E. coli) bacteria down to the concentration level of a single bacterium. The
      sensor utilizes highly enhanced plasmonic nSTFs of silver on a silicon platform
      for the enhancement of Raman bands as checked with adsorbed 4-aminothiophenol
      molecules. T-4 bacteriophages were immobilized on the aforementioned surface of
      the chip for the specific capture of target E. coli bacteria. To demonstrate that
      no significant non-specific immobilization of other bacteria occurs, three
      different, additional bacterial strains, Chromobacterium violaceum, Paracoccus
      denitrificans and Pseudomonas aeruginosa were used. Furthermore, experiments
      performed on an additional strain of E. coli to address the specificity and
      reusability of the sensor showed that the sensor operates for different strains
      of E. coli and is reusable. Time resolved phase contrast microscopy of the E.
      coli-T4 bacteriophage chip was performed to study its interaction with bacteria
      over time. Results showed that the present sensor performs a fast, accurate and
      stable detection of E. coli with ultra-small concentrations of bacteria down to
      the level of a single bacterium in 10 MUl volume of the sample. 

PMID- 25756827
TI  - Effect of silver nanoparticles on Pseudomonas putida biofilms at different stages
      of maturity.
AB  - This study determined the effect of silver nanoparticles (AgNPs) on Pseudomonas
      putida KT2440 biofilms at different stages of maturity. Three biofilm stages (1
      3, representing early to late stages of development) were identified from
      bacterial adenosine triphosphate (ATP) activity under static (96-well plate) and
      dynamic conditions (Center for Disease Control and Prevention biofilm reactor).
      Extracellular polymeric substance (EPS) levels, measured using crystal violet and
      total carbohydrate assays, and expression of the EPS-associated genes, csgA and
      alg8, supported the conclusion that biofilms at later stages were older than
      those at earlier stages. More mature biofilms (stages 2 and 3) showed little to
      no reduction in ATP activity following exposure to AgNPs. In contrast, the same
      treatment reduced ATP activity by more than 90% in the less mature stage 1
      biofilms. Regardless of maturity, biofilms with EPS stripped off were more
      susceptible to AgNPs than controls with intact EPS, demonstrating that EPS is
      critical for biofilm tolerance of AgNPs. The findings from this study show that
      stage of maturity is an important factor to consider when studying effect of
      AgNPs on biofilms. 

PMID- 25756828
TI  - Dyspareunia and sexual dysfunction after vaginal delivery in Thai primiparous
      women with episiotomy.
AB  - INTRODUCTION: Episiotomy remains commonly practiced in Thailand. There are
      limited data on its impacts on sexuality among Asian women during the first
      postdelivery year. AIMS: The aim was to study dyspareunia and sexual function at
      3-12 months after vaginal delivery in Thai primiparous women with episiotomy.
      METHODS: A total of 190 participants were approached on Day 2 postpartum. Of
      these, 93 sexually active women were evaluated for dyspareunia and sexual
      function at 3 months by using 10-cm visual analog scale and the validated Thai
      version of Female Sexual Function Index (TFSFI). TFSFI < 26.5 was defined as
      having potential sexual dysfunction. At 6 and 12 months, sexual function was
      evaluated by telephone interview. MAIN OUTCOME MEASURES: The prevalence of
      dyspareunia at 3 months and the changes of TFSFI scores during the first
      postdelivery year were the main outcome measures. RESULTS: The average age of the
      participants, over 90% of whom were high school finishers, was 24. Their partners
      were around 3 years older, and the median partnership duration was 3 years. At 3
      months, 30.1% of participants reported dyspareunia. There was no association
      between dyspareunia and the following characteristics: pre-pregnancy dyspareunia,
      newborn's head circumference and birthweight and breast-feeding (P > 0.05 for
      all). Sexual dysfunction was demonstrated in 66.7% at 3 months, 31.0% at 6
      months, and 14.9% at 12 months. From 3 to 12 months, the median TFSFI scores in
      all domains increased significantly. There was no difference of the scores in all
      domains at 3 and 12 months between women with and without dyspareunia at 3
      months. However, at 6 months, those without dyspareunia had better scores in
      pain, orgasm, satisfaction, and total scores (P < 0.05 for all). CONCLUSION:
      Dyspareunia at 3 months is common in Thai primiparous women with episiotomy.
      Those with dyspareunia have a slower resumption of normal sexual function.

PMID- 25756829
TI  - Nutritional status of care-dependent people with dementia in shared-housing
      arrangements--a one-year follow-up.
AB  - BACKGROUND: Malnutrition in the elderly is an important nursing challenge.
      Persons with dementia disease are often affected by malnutrition. During recent
      years, shared-housing arrangements (SHA) for older care-dependent people,
      frequently with dementia disease, have evolved in Germany. SHA can be an
      alternative to traditional residential care in nursing homes. The prevalence of
      malnutrition in SHA is compared to the prevalence in community dwellings and
      lower than the prevalence of malnutrition in nursing homes. There are no
      scientific data about the development of the nutritional status of older care
      dependent people in SHA over one year. The aim of this study is to describe the
      nutritional status of care-dependent people with dementia disease living in SHA
      and to investigate changes over a period of one year. METHOD: A longitudinal
      study with a one-year follow-up was performed. Standardised interviews with
      nurses were conducted concerning nutritional status (Mini Nutritional Assessment-
      MNA), cognitive capacities (Mini Mental State Examination--MMSE), activities of
      daily living (Extended Barthel-Index--EBI) and socio-demographic characteristics.
      Nutritional data were available for 45 residents at baseline and 36 residents at
      follow-up. RESULTS: At baseline, 45 residents with an average age of 78.4 years
      living in SHA in the state of Berlin, Germany, were included in the study.
      Predominantly, residents were female (73.3%) and diagnosed with dementia (88.9%),
      with a moderate to severe cognitive impairment (MMSE: 10.8) and low daily living
      abilities (EBI: 33.7). Most residents (80.6%) have a risk of malnutrition
      regarding the MNA. The average MNA score did decline slightly within one year (t0
      = 20.8 vs. t1 = 19.7). CONCLUSION: Regular screenings for malnutrition using
      validated standardised assessments, which are easy to apply, should be
      implemented in SHA to avoid nutritional and health-related problems arising from
      malnutrition. Flexible structures for care, as in SHA, can facilitate coping with
      nutritional problems.

PMID- 25756830
TI  - [Treatment of advanced non-small-cell lung cancer with driver mutations].

PMID- 25756832
TI  - Promotion or marketing of the nursing profession by nurses.
AB  - BACKGROUND: In recent years, much effort has been invested all over the world in
      nurse recruitment and retention. Issues arising in this context are low job
      satisfaction, the poor public image of nursing and the reluctance of nurses to
      promote or market their profession. AIM: This study aimed to examine factors
      explaining the marketing of the nursing profession by nurses working at a general
      tertiary medical centre in Israel. METHOD: One hundred sixty-nine registered
      nurses and midwives from five clinical care units completed a structured self
      administered questionnaire, measuring (a) professional self-image, (b) job
      satisfaction, (c) nursing promotional and marketing activity questionnaire, and
      (d) demographic data. RESULTS: The mean scores for the promotion of nursing were
      low. Nurses working in an intensive cardiac care unit demonstrated higher levels
      of promotional behaviour than nurses from other nursing wards in our study. Nurse
      managers reported higher levels of nursing promotion activity compared with first
      line staff nurses. There was a strong significant correlation between job
      satisfaction and marketing behaviour. Multiple regression analysis shows that 15%
      of the variance of promoting the nursing profession was explained by job
      satisfaction and job position. CONCLUSION: Nurses are not inclined to promote or
      market their profession to the public or to other professions. The policy on the
      marketing of nursing is inadequate. IMPLICATIONS FOR NURSING OR HEALTH POLICY: A
      three-level (individual, organizational and national) nursing marketing programme
      is proposed for implementation by nurse leadership and policy makers. Among
      proposed steps to improve marketing of the nursing profession are promotion of
      the image of nursing by the individual nurse in the course of her or his daily
      activities, formulation and implementation of policies and programmes to promote
      the image of nursing at the organizational level and drawing up of a long-term
      programme for promoting or marketing the professional status of nursing at the
      national level.

PMID- 25756831
TI  - Efficacy and safety of fixed-dose combinations of aclidinium bromide/formoterol
      fumarate: the 24-week, randomized, placebo-controlled AUGMENT COPD study.
AB  - BACKGROUND: Combining two long-acting bronchodilators with complementary
      mechanisms of action may provide treatment benefits to patients with chronic
      obstructive pulmonary disease (COPD) that are greater than those derived from
      either treatment alone. The efficacy and safety of a fixed-dose combination (FDC)
      of aclidinium bromide, a long-acting muscarinic antagonist, and formoterol
      fumarate, a long-acting beta2-agonist, in patients with moderate to severe COPD
      are presented. METHODS: In this 24-week double-blind study, 1692 patients with
      stable COPD were equally randomized to twice-daily treatment with FDC aclidinium
      400 MUg/formoterol 12 MUg (ACL400/FOR12 FDC), FDC aclidinium 400 MUg/formoterol 6
      MUg (ACL400/FOR6 FDC), aclidinium 400 MUg, formoterol 12 MUg, or placebo
      administered by a multidose dry powder inhaler (Genuair(r)/Pressair(r))*.
      Coprimary endpoints were change from baseline to week 24 in 1-hour morning
      postdose FEV1 (FDCs versus aclidinium) and change from baseline to week 24 in
      morning predose (trough) FEV1 (FDCs versus formoterol). Secondary endpoints were
      change from baseline in St. George's Respiratory Questionnaire (SGRQ) total score
      and improvement in Transition Dyspnea Index (TDI) focal score at week 24. Safety
      and tolerability were also assessed. RESULTS: At study end, improvements from
      baseline in 1-hour postdose FEV1 were significantly greater in patients treated
      with ACL400/FOR12 FDC or ACL400/FOR6 FDC compared with aclidinium (108 mL and 87
      mL, respectively; p < 0.0001). Improvements in trough FEV1 were significantly
      greater in patients treated with ACL400/FOR12 FDC versus formoterol (45 mL; p =
      0.0102), a numerical improvement of 26 mL in trough FEV1 over formoterol was
      observed with ACL400/FOR6 FDC. Significant improvements in both SGRQ total and
      TDI focal scores were observed in the ACL400/FOR12 FDC group at study end (p <
      0.0001), with differences over placebo exceeding the minimal clinically important
      difference of >=4 points and >=1 unit, respectively. All treatments were well
      tolerated, with safety profiles of the FDCs similar to those of the
      monotherapies. CONCLUSIONS: Treatment with twice-daily aclidinium 400
      MUg/formoterol 12 MUg FDC provided rapid and sustained bronchodilation that was
      greater than either monotherapy; clinically significant improvements in dyspnea
      and health status were evident compared with placebo. Aclidinium/formoterol FDC
      may be an effective and well tolerated new treatment option for patients with
      COPD. TRIAL REGISTRATION: Clinicaltrials.gov NCT01437397.

PMID- 25756833
TI  - Immunoaffinity chromatography purification and ultrahigh performance liquid
      chromatography tandem mass spectrometry determination of tetrodotoxin in marine
      organisms.
AB  - A highly selective and sensitive method was developed for the determination of
      tetrodotoxin (TTX) in marine organisms by immunoaffinity chromatography (IAC)
      purification coupled with ultrahigh performance liquid chromatography tandem mass
      spectrometry (UPLC-MS/MS). An IAC column was prepared and used to cleanup the
      extracted samples. The operating conditions of the IAC column were optimized, and
      the capacity of new IAC column was found to be 1106 ng mL(-1), which was
      sufficient for TTX determination. The MS/MS conditions and UPLC mobile phase were
      also studied to optimize the operation conditions. Fortified marine organism
      samples at levels of 0.3-5.0 ng g(-1) were utilized, and the average recoveries
      were 86.5-103.6% with intra- and inter-day relative standard deviations less than
      7.22 and 9.88%, respectively. The limits of detection and quantification were 0.1
      and 0.3 ng g(-1), respectively. The method was later successfully applied for the
      determination of TTX in 100 marine organism samples collected from local markets.

PMID- 25756834
TI  - Iridium-catalyzed reductive carbon-carbon bond cleavage reaction on a curved
      pyridylcorannulene skeleton.
AB  - The cleavage of C?C bonds in pi-conjugated systems is an important method for
      controlling their shape and coplanarity. An efficient way for the cleavage of an
      aromatic C?C bond in a typical buckybowl corannulene skeleton is reported. The
      reaction of 2-pyridylcorannulene with a catalytic amount of IrCl3 ?n H2 O in
      ethylene glycol at 250  degrees C resulted in a structural transformation from
      the curved corannulene skeleton to a strain-free flat benzo[ghi]fluoranthene
      skeleton through a site-selective C?C cleavage reaction. This cleavage reaction
      was found to be driven by both the coordination of the 2-pyridyl substituent to
      iridium and the relief of strain in the curved corannulene skeleton. This finding
      should facilitate the design of carbon nanomaterials based on C?C bond cleavage
      reactions. 

PMID- 25756835
TI  - Collaboration, not competition: cost analysis of neonatal nurse practitioner plus
      neonatologist versus neonatologist-only care models.
AB  - BACKGROUND: Although advanced practice in neonatal nursing is accepted and
      supported by the American Academy of Pediatrics and National Association of
      Neonatal Nurse Practitioners, less than one-half of all states allow independent
      prescriptive authority by advanced practice nurse practitioners. PURPOSE: The
      purpose of this study was to compare costs of a collaborative practice model that
      includes neonatal nurse practitioner (NNP) plus neonatologist (Neo) versus a
      neonatologist only (Neo-Only) practice in Washington state. Published Internet
      median salary figures from 3 sources were averaged to produce mean +/- SD
      provider salaries, and costs for each care model were calculated in this
      descriptive, comparative study. FINDINGS/RESULTS: Median NNP versus Neo salaries
      were $99,773 +/- $5206 versus $228,871 +/- $9654, respectively (P < .0001). The
      NNP + Neo (5 NNP/3 Neo full-time equivalents [FTEs]) cost $1,185,475 versus Neo
      Only (8 Neo FTEs) cost $1,830,960. The NNP + Neo practice model with 8 FTEs
      suggests a cost savings, with assumed equivalent reimbursement, of $645,485/year.
      IMPLICATIONS FOR PRACTICE: These results may provide the impetus for more states
      to adopt broader scope of practice licensure for NNPs. IMPLICATIONS FOR RESEARCH:
      These data may provide rationale for analysis of actual costs and outcomes of
      collaborative practice.

PMID- 25756836
TI  - Interactions of arabinoxylan and (1,3)(1,4)-beta-glucan with cellulose networks.
AB  - To identify interactions of relevance to the structure and properties of the
      primary cell walls of cereals and grasses, we used arabinoxylan and (1,3)(1,4)
      beta-glucan, major polymers in cereal/grass primary cell walls, to construct
      composites with cellulose produced by Gluconacetobacter xylinus. Both polymers
      associated prolifically with cellulose without becoming rigid or altering the
      nature or extent of cellulose crystallinity. Mechanical properties were modestly
      affected compared with xyloglucan or pectin (characteristic components of
      nongrass primary cell walls) composites with cellulose. In situ depletion of
      arabinoxylan arabinose side chains within preformed cellulose composites resulted
      in phase separation, with only limited enhancement of xylan-cellulose
      interactions. These results suggest that arabinoxylan and (1 -> 3)(1 -> 4)-beta-d
      glucan are not functional homologues for either xyloglucan or pectin in the way
      they interact with cellulose networks. Association of cell-wall polymers with
      cellulose driven by entropic amelioration of high energy cellulose/water
      interfaces should be considered as a third type of interaction within cellulose
      based cell walls, in addition to molecular binding (enthalpic driving force)
      exhibited by, for example, xyloglucans or mannans, and interpenetrating networks
      based on, for example, pectins. 

PMID- 25756837
TI  - Family acceptability of school-based echocardiographic screening for rheumatic
      heart disease in a high-risk population in New Zealand.
AB  - AIM: Echocardiographic screening for rheumatic heart disease has been piloted in
      high-risk areas in New Zealand and internationally, and fulfils most of the
      criteria for a targeted screening programme. The question of acceptability of
      rheumatic heart disease screening has not been assessed, and the aim of our study
      was to assess parental acceptability of a school-based echocardiographic
      screening programme in a high-risk population in New Zealand. METHODS: A post
      screening questionnaire was developed to survey parents of children who underwent
      echocardiographic screening. The families of 34 children with abnormal scan
      results and a sample of 80 children with normal scan results were surveyed by
      phone within 4 months of screening. RESULTS: Positive results were seen in all
      survey questions in both normal and abnormal scan groups. All families were
      supportive of an ongoing screening programme. Of children with abnormal results,
      62% of their parents reported that they would treat their child differently;
      however, all responses were positive health-promoting outcomes. CONCLUSION: The
      study showed strong positive support for school-based echocardiographic screening
      by a community with high acute rheumatic fever incidence. The study did not
      detect any short-term negative effects in those with abnormal results. The survey
      result shows family and community support for the establishment of
      echocardiographic screening programmes in high acute rheumatic fever areas
      provided there is adequate infrastructural support.

PMID- 25756838
TI  - The effects of implementing the International Association of Diabetes and
      Pregnancy Study Groups criteria for diagnosing gestational diabetes on maternal
      and neonatal outcomes.
AB  - BACKGROUND: In 2010, the International Association of the Diabetes and Pregnancy
      Study Groups (IADPSG) recommended a new strategy for the screening and diagnosis
      of gestational diabetes mellitus (GDM). However, no study has indicated that
      adopting the IADPSG recommendations improves perinatal outcomes. The objective of
      this study was to evaluate the effects of implementing the IADPSG criteria for
      diagnosing GDM on maternal and neonatal outcomes. METHODOLOGY/PRINCIPAL FINDINGS:
      Previously, we used a two-step approach (a 1-h, 50-g glucose challenge test
      followed by a 3-h, 100-g glucose tolerance test when indicated) to screen for and
      diagnose GDM. In July 2011, we adopted the IADPSG recommendations in our routine
      obstetric care. In this study, we retrospectively compared the rates of various
      maternal and neonatal outcomes in all women who delivered after 24 weeks of
      gestation during the periods before (P1, between January 1, 2009 and December 31,
      2010) and after (P2, between January 1, 2012 and December 31, 2013) the IADPSG
      criteria were implemented. Pregnancies complicated by multiple gestations, fetal
      chromosomal or structural anomalies, and pre-pregnancy diabetes mellitus were
      excluded. Our results showed that the incidence of GDM increased from 4.6% using
      the two-step method to 12.4% using the IADPSG criteria. Compared to the women in
      P1, the women in P2 experienced less weight gain during pregnancy, lower birth
      weights, shorter labor courses, and lower rates of macrosomia (<4000 g) and large
      for-gestational age (LGA) infants. P2 was a significant independent factor
      against macrosomia (adjusted odds ratio [OR] 0.63, 95% confidence interval [CI]
      0.43-0.90) and LGA (adjusted OR 0.74, 95% CI 0.61-0.89) after multivariable
      logistic regression analysis. CONCLUSIONS/SIGNIFICANCE: The adoption of the
      IADPSG criteria for diagnosis of GDM was associated with significant reductions
      in maternal weight gain during pregnancy, birth weights, and the rates of
      macrosomia and LGA.

PMID- 25756839
TI  - In vitro susceptibility testing of amphotericin B for Cryptococcus neoformans
      variety grubii AFLP1/VNI and Cryptococcus gattii AFLP6/VGII by CLSI and flow
      cytometry.
AB  - Cryptococcus neoformans var. grubii AFLP1/VNI is the main causative agent of
      cryptococcosis associated with AIDS in the world. Cryptococcus gattii AFLP6/VGII
      causes mainly endemic primary infection in immunocompetent hosts. To determine
      the minimum inhibitory concentrations (MICs) of C. neoformans var. grubii
      AFLP1/VNI and C. gattii AFLP6/VGII against amphotericin B (AMB) in a short period
      of time, flow cytometry (FCM) with FUN-1 fluorochrome was used to compare with
      broth microdilution method (CLSI M27-A3). The minimum incubation period was
      evaluated by minimum fungicidal concentration procedure. Seventeen clinical
      isolates of C. neoformans var. grubii AFLP1/VNI and 18 of C. gattii AFLP6/VGII
      were analysed. The time for the determination of MICs by FCM was 2 h against 72 h
      by CLSI M27-A3 and the comparison of MIC showed a positive significant
      correlation (P = 0.048). It is important to highlight the role of the FCM as an
      alternative method to determine the MICs for AMB in within a day, with positive
      cost-benefit.

PMID- 25756840
TI  - Screening for Primary Aldosteronism: Whom and How?

PMID- 25756841
TI  - Using signal detection theory in the analysis of emotional sensitivity of male
      recidivist offenders.
AB  - BACKGROUND: Study of emotional responses of antisocial individuals has produced
      inconsistent findings. Some studies report emotional deficits, while others find
      no differences between people with and without antisocial behaviours. AIMS: Our
      aim was to apply signal detection theory methods to compare the sensitivity of
      antisocial and control participants to emotional stimuli. We hypothesised that
      offenders would show lower ability to discriminate changes in the level of
      arousal and valence of emotional stimuli relative to the controls. METHODS:
      Signal detection theory was applied to study the sensitivity of recidivist
      offenders in prison to emotional arousal and valence induced by pictures. This
      approach, novel in this context, provides a departure from the usual reliance on
      self-report. RESULTS: Offenders reported higher arousal than controls but showed
      lower sensitivity to changes between different levels of arousal (whereas no
      differences were found for valence). Also, offenders showed increased response
      bias for changes in the levels of arousal, as well as in the higher levels of
      valence. CONCLUSIONS: Our findings show that direct observations of emotional
      arousal, but not valence, discriminate between recidivist offenders with
      antisocial personality disorder and non-offending controls. Use of such
      approaches is likely to provide more valid data than self-reports and may prove
      particularly useful in studies of intervention for recidivists or in assessment
      of their readiness for release.

PMID- 25756842
TI  - Coronary bypass surgery in the presence of metastatic pheochromocytoma.
AB  - The hemodynamic management of a patient with a pheochromocytoma presents special
      challenges due to the episodic release of catecholamines from the tumor, which
      threatens to provoke a hypertensive crisis. We present a patient with metastatic
      pheochromocytoma (bone, lung, lymph nodes) who underwent successful coronary
      artery bypass graft (CABG) surgery following premedication with phenoxybenzamine
      and metyrosine as well as the use of intraoperative phentolamine for the
      management of a hypertensive crisis in the operating room.

PMID- 25756843
TI  - Insight into the structure and functional application of the Sr0.95Ce0.05CoO3
      delta cathode for solid oxide fuel cells.
AB  - A new perovskite cathode, Sr0.95Ce0.05CoO3-delta, performs well for oxygen
      reduction reactions in solid oxide fuel cells (SOFCs). We gain insight into the
      crystal structure of Sr1-xCexCoO3-delta (x = 0.05, 0.1) and temperature-dependent
      structural evolution of Sr0.95Ce0.05CoO3-delta by X-ray diffraction, neutron
      powder diffraction, and scanning transmission electron microscopy experiments.
      Sr0.9Ce0.1CoO3-delta shows a perfectly cubic structure (a = a0), with a large
      oxygen deficiency in a single oxygen site; however, Sr0.95Ce0.05CoO3-delta
      exhibits a tetragonal perovskite superstructure with a double c axis, defined in
      the P4/mmm space group, that contains two crystallographically different cobalt
      positions, with distinct oxygen environments. The structural evolution of
      Sr0.95Ce0.05CoO3-delta at high temperatures was further studied by in situ
      temperature-dependent NPD experiments. At 1100 K, the oxygen atoms in
      Sr0.95Ce0.05CoO3-delta show large and highly anisotropic displacement factors,
      suggesting a significant ionic mobility. The test cell with a
      La0.8Sr0.2Ga0.83Mg0.17O3-delta-electrolyte-supported (~300 MUm thickness)
      configuration yields peak power densities of 0.25 and 0.48 W cm(-2) at
      temperatures of 1023 and 1073 K, respectively, with pure H2 as the fuel and
      ambient air as the oxidant. The electrochemical impedance spectra evolution with
      time of the symmetric cathode fuel cell measured at 1073 K shows that the
      Sr0.95Ce0.05CoO3-delta cathode possesses superior ORR catalytic activity and long
      term stability. Mixed ionic-electronic conduction properties of Sr0.95Ce0.05CoO3
      delta account for its good performance as an oxygen-reduction catalyst. 

PMID- 25756844
TI  - Comparison of outcomes after hospitalization for worsening heart failure,
      myocardial infarction, and stroke in patients with heart failure and reduced and
      preserved ejection fraction.
AB  - AIMS: To investigate the prognostic significance of hospitalization for worsening
      heart failure (WHF), myocardial infarction (MI), and stroke in patients with
      chronic heart failure (HF). METHODS AND RESULTS: We studied 5011 patients with HF
      and reduced EF (HF-REF) in the CORONA trial and 4128 patients with HF and
      preserved EF (HF-PEF) in the I-Preserve trial. Adjusted hazard ratios (HRs) for
      death were estimated for 0-30 days and >=31 days after first post-randomization
      WHF, MI, or stroke used as a time-dependent variable, compared with patients with
      none of these events. In CORONA, 1616 patients (32%) had post-randomization first
      events (1223 WHF, 216 MI, 177 stroke), and the adjusted HR for mortality <=30
      days after an event was: WHF 7.21 [95% confidence interval (CI) 2.05-25.40], MI
      23.08 (95% CI 6.44-82.71), and stroke 32.15 (95% CI 8.93-115.83). The HR for
      mortality at >30 days was: WHF 3.62 (95% CI 3.11-4.21), MI 4.41 (95% CI 3.23
      6.02), and stroke 3.19 (95% CI 2.21-4.61). In I-Preserve, 896 patients (22%)
      experienced a post-randomization event (638 WHF, 111 MI, 147 stroke). The HR for
      mortality <=30 days was WHF 31.77 (95% CI 7.60-132.81), MI 154.77 (95% CI 34.21
      700.17), and stroke 223.30 (95% CI 51.42-969.78); for >30 days it was WHF 3.36
      (95% CI 2.79-4.05), MI 3.29 (95% CI 2.14-5.06), and stroke 5.13 (95% CI 3.61
      7.29). CONCLUSIONS: In patients with both HF-REF and HF-PEF, hospitalization for
      WHF was associated with high early and late mortality. The early relative risk of
      death was not as great as following MI or stroke, but the longer term relative
      risk of death was similar following all three types of event. Numerically, more
      deaths occurred following WHF because it was a much more common event.

PMID- 25756845
TI  - Motor-vehicle collisions involving child pedestrians at intersection and mid
      block locations.
AB  - We study motor-vehicle collisions involving child pedestrians walking to school
      in Hamilton, Ontario, Canada to understand and contrast collision risks at mid
      block and intersection locations. We use a matched case-control study design and
      apply it to intersection and mid-block locations instead of people. Cases are
      intersections/mid-blocks where collisions occurred and controls are locations
      where collisions did not occur. We match cases to controls on geography, socio
      economic status and year. We use conditional logistic regression to predict the
      log-odds of collision risk at intersections and mid-blocks as a function of
      various environmental measures while controlling for volume of child pedestrian
      activity. Our results suggest that child pedestrian injuries at intersections are
      associated with intersection control type, traffic volume, and land use
      characteristics. In contrast, mid-block child pedestrian collisions are not
      associated with small scale environmental features. The results of this study
      suggest that some factors associated with the risk of collision differ across
      location types. These findings may be useful in the planning of safer walking
      journeys to school. 

PMID- 25756847
TI  - Effects of driver age and experience in abrupt-onset hazards.
AB  - Novice drivers and older drivers are found to have the highest crash risk among
      all drivers and this has motivated many research studies into various aspects of
      novice and older drivers. Although age-related declines were expected, studies
      did not find older drivers to respond slower to hazards. This study examined the
      hazard detection and response latencies of 14 young novice drivers, 14 young
      experienced drivers, and 12 older experienced drivers, to abrupt-onset hazards.
      Older drivers were found to take longer times before fixating on an abrupt-onset
      road hazard but appeared to have insignificantly faster reaction times after the
      initial fixation. Hence, the overall response latency did not suggest any age
      effects. Older drivers also scanned the roadway less as compared to their younger
      counterparts. No effects of experience were found. The findings provided insight
      on age-related declines in hazard detection whose effects have been masked by
      other components of hazard response. 

PMID- 25756846
TI  - Association between alcohol-impaired driving enforcement-related strategies and
      alcohol-impaired driving.
AB  - All states in the U.S. prohibit alcohol-impaired driving but active law
      enforcement is necessary for effectively reducing this behavior. Sobriety
      checkpoints, saturation patrols, open container laws, and media campaigns related
      to enforcement efforts are all enforcement-related strategies for reducing
      alcohol-impaired driving. We conducted surveys of all state patrol agencies and a
      representative sample of local law enforcement agencies to assess their use of
      alcohol-impaired driving enforcement-related strategies and to determine the
      relationship between these enforcement-related strategies and self-reported
      alcohol-impaired driving behavior obtained from the Behavioral Risk Factor
      Surveillance System. We found that sobriety checkpoints, saturation patrols, and
      enforcement of open container laws were associated with a lower prevalence of
      alcohol-impaired driving but, more importantly, a combination of enforcement
      related strategies was associated with a greater decrease in alcohol-impaired
      driving than any individual enforcement-related activity. In addition, alcohol
      impaired driving enforcement-related strategies were associated with decreased
      alcohol-impaired driving above and beyond their association with decreased binge
      drinking. Results suggest law enforcement agencies should give greater priority
      to using a combination of strategies rather than relying on any one individual
      enforcement activity. 

PMID- 25756848
TI  - Combination therapy with human umbilical cord mesenchymal stem cells and
      angiotensin-converting enzyme 2 is superior for the treatment of acute lung
      ischemia-reperfusion injury in rats.
AB  - Acute lung ischemia-reperfusion injury (ALIRI) is a serious disease that
      seriously affects human's life. In this study, we aimed to explore a more
      effective treatment method by combining human umbilical cord mesenchymal stem
      cells (HUMSCs) and angiotensin-converting enzyme 2 (ACE2) for ALIRI. Fifty rats
      were firstly divided into five groups, namely sham surgery group (sham) and four
      model groups (model, ACE2, HUMSCs and HUMSCs + ACE2) that were reperfused with
      0.1 ml physiological saline (PS), 0.1 ml PS containing 1 * 10(6) lentiviral
      ACE2/HUMSCs/ACE2 + UMSCs, respectively. Quantitative reverse transcription-PCR
      (qRT-PCR) and western blot assays were then conducted to detect the messenger RNA
      (mRNA) and protein levels of inflammatory cytokines [intercellular adhesion
      molecule 1 (ICAM-1), vascular cell adhesion molecule 1 (VCAM-1), tumour necrosis
      factor alpha (TNF-alpha), nuclear factor kappaB (NF-kappaB), platelet-derived
      growth factor (PDGF) and angiotensin II (Ang II)], antioxidant proteins [NAD(P)H
      quinone oxidoreductase 1 (NQO1), heme oxygenase 1 (HO-1)], DNA damage and
      apoptotic indicators [BCL2-associated X (Bax), cleaved caspase-3 (C-Csp 3),
      cleaved-poly(ADP-ribose) polymerase (C-PARP), Y-H2AX], anti-apoptotic indicator
      (Bcl-2) and smooth muscle cell proliferation indicator [connexin 43 (Cx43)].
      According to the qRT-PCR and western results, the mRNA and protein expression
      levels of ICAM-1, VCAM-1, TNF-alpha, NF-kappaB, PDGF, Bax, C-Csp 3, C-PARP and Y
      H2AX were significantly higher in model group than those in sham group and they
      were significantly reduced by HUMSCs or ACE2 treatment (P < 0.05). On the
      contrary, Bcl-2 showed an opposite expression trend with the previous proteins.
      The mRNA and protein levels of NQO1 and HO-1 were sequentially increased in sham,
      model, ACE2, HUMSCs and HUMSCs + ACE2 groups. Besides, HUMSCs combined with ACE2
      exhibited a better inhibition effect on ALIRI than HUMSCs or ACE2 alone (P <
      0.05). In summary, HUMSCs combined with ACE2 was demonstrated to have the best
      therapeutic effect on ALIRI through anti-inflammation, oxidative stress and anti
      apoptotic processes.

PMID- 25756849
TI  - The development, implementation and evaluation of clinical practice guidelines in
      Gulf Cooperation Council (GCC) countries: a systematic review of literature.
AB  - RATIONALE, AIMS AND OBJECTIVES: Our aim was to examine and describe the current
      situation in Gulf Cooperation Council (GCC) member countries regarding the
      development, implementation and evaluation of clinical practice guidelines (CPG).
      The objectives were to describe from where the studies originated, what the
      clinical focus was of each study and examine the methodology and the status of
      each study (i.e. development, dissemination, implementation and evaluation).
      METHODS: Review of literature - two stages: stage 1: screening through an
      abstract review, followed by independent adjudicator; stage 2: detailed
      assessment and classification. RESULTS: Considering the widespread acceptance
      that CPG's are useful and effective tools for quality improvement in health care,
      it is worth noting that relatively few studies have been conducted in the GCC
      region that examine CPG. Furthermore, the reviewers found that the quality of the
      research methods used could be improved. The majority of the studies that were
      conducted evaluated the effects of guidelines and focused on the 'lifestyle
      diseases', in particular diabetes and cardiovascular diseases. It is also worth
      noting that there has been a steady increase in the number of publications over
      the 10 years period. CONCLUSIONS: More attention needs to be given to developing,
      disseminating, implementing and evaluating CPG's in the GCC region in order to
      improve the quality and safety of health care.

PMID- 25756850
TI  - H and D attachment to naphthalene: spectra and thermochemistry of cold gas-phase
      1-C10H9 and 1-C10H8D radicals and cations.
AB  - Excitation spectra of the 1H-naphthalene (1-C10H9) and 1D-naphthalene (1-C10H8D)
      radicals, and their cations, are obtained by laser spectroscopy and mass
      spectrometry of a skimmed free-jet expansion following an electrical discharge.
      The spectra are assigned on the basis of density functional theory calculations.
      Isotopic shifts in origin transitions, vibrational frequencies and ionization
      energies were found to be well reproduced by (time-dependent) density functional
      theory. Absolute bond dissociation energies, ionization energies and proton
      affinities were calculated using high-level quantum chemical methods. 

PMID- 25756851
TI  - The metal-organic framework MIL-53(Al) constructed from multiple metal sources:
      alumina, aluminum hydroxide, and boehmite.
AB  - Three aluminum compounds, namely alumina, aluminum hydroxide, and boehmite, are
      probed as the metal sources for the hydrothermal synthesis of a typical metal
      organic framework MIL-53(Al). The process exhibits enhanced synthetic efficiency
      without the generation of strongly acidic byproducts. The time-course monitoring
      of conversion from different aluminum sources into MIL-53(Al) is achieved by
      multiple characterization that reveals a similar but differentiated
      crystallinity, porosity, and morphology relative to typical MIL-53(Al) prepared
      from water-soluble aluminum salts. Moreover, the prepared MIL-53(Al) constructed
      with the three insoluble aluminum sources exhibit an improved thermal stability
      of up to nearly 600  degrees C and enhanced yields. Alumina and boehmite are more
      preferable than aluminum hydroxide in terms of product porosity, yield, and
      reaction time. The adsorption performances of a typical environmental endocrine
      disruptor, dimethyl phthalate, on the prepared MIL-53(Al) samples are also
      investigated. The improved structural stability of MIL-53(Al) prepared from these
      alternative aluminum sources enables double-enhanced adsorption performance (up
      to 206 mg g(-1)) relative to the conventionally obtained MIL-53(Al).

PMID- 25756852
TI  - Bayesian sequential monitoring design for two-arm randomized clinical trials with
      noncompliance.
AB  - In early-phase clinical trials, interim monitoring is commonly conducted based on
      the estimated intent-to-treat effect, which is subject to bias in the presence of
      noncompliance. To address this issue, we propose a Bayesian sequential monitoring
      trial design based on the estimation of the causal effect using a principal
      stratification approach. The proposed design simultaneously considers efficacy
      and toxicity outcomes and utilizes covariates to predict a patient's potential
      compliance behavior and identify the causal effects. Based on accumulating data,
      we continuously update the posterior estimates of the causal treatment effects
      and adaptively make the go/no-go decision for the trial. Numerical results show
      that the proposed method has desirable operating characteristics and addresses
      the issue of noncompliance.

PMID- 25756853
TI  - RoY peptide-modified chitosan-based hydrogel to improve angiogenesis and cardiac
      repair under hypoxia.
AB  - Myocardial infarction (MI) still represents the "Number One Killer" in the world.
      The lack of functional vasculature of the infracted myocardium under hypoxia is
      one of the main problems for cardiac repair. In this study, a thermosensitive
      chitosan chloride-RoY (CSCl-RoY) hydrogel was developed to improve angiogenesis
      under hypoxia after MI. First, RoY peptides were conjugated onto the CSCl chain
      via amide linkages, and our data show that the conjugation of RoY peptide to CSCl
      does not interfere with the temperature sensitivity. Then, the effect of CSCl-RoY
      hydrogels on vascularization in vitro under hypoxia was investigated using human
      umbilical vein endothelial cells (HUVECs). Results show that CSCl-RoY hydrogels
      can promote the survival, proliferation, migration and tube formation of HUVECs
      under hypoxia compared with CSCl hydrogel. Further investigations suggest that
      CSCl-RoY hydrogels can modulate the expression of membrane surface GRP78 receptor
      of HUVECs under hypoxia and then activate Akt and ERK1/2 signaling pathways
      related to cell survival/proliferation, thereby enhancing angiogenic activity of
      HUVECs under hypoxia. To assess its therapeutic properties in vivo, a MI model
      was induced in rats by the left anterior descending artery ligation. CSCl or CSCl
      RoY hydrogels were injected into the border of infracted hearts. The results
      demonstrate that the introduction of RoY peptide can not only improve
      angiogenesis at MI region but also improve the cardiac functions. Overall, we
      conclude that the CSCl-RoY may represent an ideal scaffold material for
      injectable cardiac tissue engineering. 

PMID- 25756855
TI  - Syntheses, structures, and properties of a series of novel high-nuclear 3d-4f
      clusters with mixed amino acids as ligands: {Ln6Cu24}(Ln = Gd, Tb, Pr and Sm).
AB  - The first examples of high-nuclear 3d-4f heterometallic clusters with mixed amino
      acid ligands are reported. Four 30-nuclear clusters {Ln6Cu24}(Ln = Gd, Tb, Pr and
      Sm) were obtained through the self-assembly of Ln(III), Cu(II) and mixed amino
      acid ligands of glycine (HGly) and beta-alanine (HAla). The metal skeleton of
      clusters may be described as a huge {Ln6Cu12} octahedron connected with 12
      additional Cu(II) ions. The temperature dependence of magnetic susceptibilities
      of compounds were also studied. 

PMID- 25756854
TI  - Clinical Features and Treatment Outcomes of Bloodstream Infections Caused by
      Extended-Spectrum beta-Lactamase-Producing Escherichia coli Sequence Type 131.
AB  - Despite the remarkable emergence of extended-spectrum beta-lactamase (ESBL)
      producing Escherichia coli sequence type 131 (ST131), the clinical features and
      outcomes of infections caused by ST131 remain poorly described. From 2011 to
      2012, we collected ESBL-producing E. coli isolates from patients with bloodstream
      infections in 13 hospitals in Korea and compared clinical characteristics and
      outcomes between ST131 and non-ST131 clones. Of the 110 ESBL-producing isolates,
      the most common ST was ST131 (30.9%). Multivariate analysis showed that recent
      operation was the only variable associated with the ST131 clone; other comorbid
      conditions and clinical features were similar between ST131 and non-ST131 clones.
      CTX-M-14 and CTX-M-15 were the predominant types of ESBLs, and CTX-M-15 was
      significantly associated with ST131. The rate of nonsusceptibility to
      ciprofloxacin was higher in ST131 than in non-ST131 clones (94.1% vs. 75.0%). No
      significant differences in 30-day mortality rates were found between ST131 and
      non-ST131 clones. Multivariate analysis revealed that older age (odds ratio
      [OR]=5.39, 95% confidence interval [CI] 1.22-23.89; p=0.027), nosocomial
      infection (OR=4.81, 95% CI 1.15-20.15; p=0.032), and higher Pitt bacteremia score
      (OR=7.26, 95% CI 1.41-37.42; p=0.018) were independent risk factors for 30-day
      mortality. The ESBL-producing E. coli ST131 clone has emerged and disseminated in
      Korea. Our findings reveal similarities in clinical and demographic
      characteristics between ST131 and non-ST131 clones. Although a more resistant
      profile has been detected in ST131, patients with the ST131 clone did not exhibit
      a higher mortality rate. 

PMID- 25756856
TI  - Thiolate-bridged dinuclear ruthenium and iron complexes as robust and efficient
      catalysts toward oxidation of molecular dihydrogen in protic solvents.
AB  - Thiolate-bridged dinuclear ruthenium and iron complexes are found to work as
      efficient catalysts toward oxidation of molecular dihydrogen in protic solvents
      such as water and methanol under ambient reaction conditions. Heterolytic
      cleavage of the coordinated molecular dihydrogen at the dinuclear complexes and
      the sequential oxidation of the produced hydride complexes are involved as key
      steps to promote the present catalytic reaction. The catalytic activity of the
      dinuclear complexes toward the chemical oxidation of molecular dihydrogen
      achieves up to 10000 TON (turnover number), and electrooxidation of molecular
      dihydrogen proceeds quite rapidly. The result of the density functional theory
      (DFT) calculation on the reaction pathway indicates that a synergistic effect
      between the two ruthenium atoms plays an important role to realize the catalytic
      oxidation of molecular dihydrogen efficiently. The present dinuclear ruthenium
      complex is found to work as an efficient organometallic anode catalyst for the
      fuel cell. It is noteworthy that the present dinuclear complex worked not only as
      an effective catalyst toward chemical and electrochemical oxidation of molecular
      dihydrogen but also as a good anode catalyst for the fuel cell. We consider that
      the result described in this paper provides useful and valuable information to
      develop highly efficient and low-cost transition metal complexes as anode
      catalysts in the fuel cell. 

PMID- 25756857
TI  - PRAGMA-CF. A Quantitative Structural Lung Disease Computed Tomography Outcome in
      Young Children with Cystic Fibrosis.
AB  - RATIONALE: Chest computed tomography (CT) is the gold standard for demonstrating
      cystic fibrosis (CF) airway disease. However, there are no standardized outcome
      measures appropriate for children younger than 6 years. OBJECTIVES: We developed
      the Perth-Rotterdam Annotated Grid Morphometric Analysis for CF (PRAGMA-CF), a
      quantitative measure of airway disease, and compared it with the commonly used CF
      CT scoring method. METHODS: CT scans from the Australian Respiratory Early
      Surveillance Team for CF (AREST CF) cohort in Western Australia were included.
      PRAGMA-CF was performed by annotating a grid overlaid on 10 axial slices for the
      presence of bronchiectasis, mucous plugging, or other airway abnormalities
      (inspiratory scans) and trapped air (expiratory scans). The separate proportions
      of total disease (%Dis), bronchiectasis (%Bx), and trapped air (%TA) were
      determined. Thirty scans were used for observer reliability, and 30 paired scans
      obtained at 1 and 3 years old were used for comparison with a validated standard
      and biologic plausibility. MEASUREMENTS AND MAIN RESULTS: Intraobserver,
      intraclass correlation coefficients (95% confidence interval) for %Dis, %Bx, and
      %TA were 0.93 (0.86-0.97), 0.93 (0.85-0.96), and 0.96 (0.91-0.98), respectively.
      The change in %Dis (P = 0.004) and %Bx (P = 0.001) with PRAGMA-CF was related to
      neutrophil elastase presence at age 3, whereas only the change in bronchiectasis
      score was related to neutrophil elastase (P < 0.001) with CF-CT. Sample-size
      calculations for various effect sizes are presented. CONCLUSIONS: PRAGMA-CF is a
      sensitive and reproducible outcome measure for assessing the extent of lung
      disease in very young children with CF.

PMID- 25756858
TI  - Inhibition of calpain prevents manganese-induced cell injury and alpha-synuclein
      oligomerization in organotypic brain slice cultures.
AB  - Overexposure to manganese has been known to promote alpha-synuclein
      oligomerization and enhance cellular toxicity. However, the exact mechanism of Mn
      induced alpha-synuclein oligomerization is unclear. To explore whether alpha
      synuclein oligomerization was associated with the cleavage of alpha-synuclein by
      calpain, we made a rat brain slice model of manganism and pretreated slices with
      calpain inhibitor II, a cell-permeable peptide that restricts the activity of
      calpain. After slices were treated with 400 MUM Mn for 24 h, there were
      significant increases in the percentage of apoptotic cells, lactate dehydrogenase
      release, intracellular [Ca2+]i, calpain activity, and the mRNA and protein
      expression of calpain 1 and alpha-synuclein. Moreover, the number of C- and N
      terminal fragments of alpha-synuclein and the amount of alpha-synuclein
      oligomerization also increased. These results also showed that calpain inhibitor
      II pretreatment could reduce Mn-induced nerve cell injury and alpha-synuclein
      oligomerization. Additionally, there was a significant decrease in the number of
      C- and N-terminal fragments of alpha-synuclein in calpain inhibitor II-pretreated
      slices. These findings revealed that Mn induced the cleavage of alpha-synuclein
      protein via overactivation of calpain and subsequent alpha-synuclein
      oligomerization in cultured slices. Moreover, the cleavage of alpha-synuclein by
      calpain 1 is an important signaling event in Mn-induced alpha-synuclein
      oligomerization. 

PMID- 25756859
TI  - Simultaneous enhancement of upconversion and downshifting luminescence via
      plasmonic structure.
AB  - We describe a metal nanodisk-insulator-metal (MIM) structure that enhances
      lanthanide-based upconversion (UC) and downshifting (DS) simultaneously. The
      structure was fabricated using a nanotransfer printing method that facilitates
      large-area applications of nanostructures for optoelectronic devices. The
      proposed MIM structure is a promising way to harness the entire solar spectrum by
      converting both ultraviolet and near-infrared to visible light concurrently
      through resonant-mode excitation. The overall photoluminescence enhancements of
      the UC and DS were 174- and 29-fold, respectively. 

PMID- 25756860
TI  - Characterization and Inductive Expression Analysis of Interferon Gamma-Related
      Gene in the Indian Major Carp, Rohu (Labeo rohita).
AB  - Interferon gamma (IFN-gamma) is one of the key cytokines that plays a major role
      against viral and intracellular bacterial infection. In addition to the IFN-gamma
      gene, teleost fish possess a second copy known as IFN-gamma-related (IFN
      gammarel) gene. This report describes structural and functional properties of IFN
      gammarel gene in the Indian major carp, rohu (Labeo rohita), a commercially
      important freshwater fish species in the Indian subcontinent. The rohu IFN
      gammarel gene consisted of four exons with three intervening introns and
      phylogenetically closely related to grass carp. The full-length IFN-gammarel cDNA
      comprised 927 bp nucleotides with a single open reading frame of 504 bp, encoding
      167 amino acids (aa) polypeptide with a signal peptide of 24 aa. The mature rohu
      IFN-gammarel protein was 143 aa with a predicted molecular weight of 16.85 kDa.
      Basal expression analysis of IFN-gammarel showed its wide range of expression in
      all examined tissues: The highest was in the skin and the lowest was in the
      liver. In response to LPS, poly I:C, iE-DAP, muramyl dipeptide stimulations, and
      bacterial infections, IFN-gammarel gene expression was significantly (p<0.05)
      induced in treated fish tissues as compared with their control. The IFN-gammarel
      was expressed as recombinant protein (rIFN-gammarel) and confirmed through
      western blot. Stimulation of peripheral blood leukocytes with rIFN-gammarel
      protein resulted in the activation of IFN-gamma receptor and marked induction of
      inducible nitric oxide synthase gene expression. These results together may
      suggest the important role of IFN-gammarel as an antimicrobial cytokine in fish.

PMID- 25756861
TI  - An approach to precise nitrogen management using hand-held crop sensor
      measurements and winter wheat yield mapping in a Mediterranean environment.
AB  - Regardless of the crop production system, nutrients inputs must be controlled at
      or below a certain economic threshold to achieve an acceptable level of
      profitability. The use of management zones and variable-rate fertilizer
      applications is gaining popularity in precision agriculture. Many researchers
      have evaluated the application of final yield maps and geo-referenced geophysical
      measurements (e.g., apparent soil electrical conductivity-ECa) as a method of
      establishing relatively homogeneous management zones within the same plot. Yield
      estimation models based on crop conditions at certain growth stages, soil
      nutrient statuses, agronomic factors, moisture statuses, and weed/pest pressures
      are a primary goal in precision agriculture. This study attempted to achieve the
      following objectives: (1) to investigate the potential for predicting winter
      wheat yields using vegetation measurements (the Normalized Difference Vegetation
      Index-NDVI) at the beginning of the season, thereby allowing for a yield response
      to nitrogen (N) fertilizer; and (2) evaluate the feasibility of using inexpensive
      optical sensor measurements in a Mediterranean environment. A field experiment
      was conducted in two commercial wheat fields near Seville, in southwestern Spain.
      Yield data were collected at harvest using a yield monitoring system (RDS Ceres
      II-volumetric meter) installed on a combine. Wheat yield and NDVI values of 3498
      +/- 481 kg ha(-1) and 0.67 +/- 0.04 nm nm(-1) (field 1) and 3221 +/- 531 kg ha(
      1) and 0.68 +/- 0.05 nm nm(-1) (field 2) were obtained. In both fields, the yield
      and NDVI exhibited a strong Pearson correlation, with r(xy) = 0.64 and p < 10(-4)
      in field 1 and r(xy) = 0.78 and p < 10(-4) in field 2. The preliminary results
      indicate that hand-held crop sensor-based N management can be applied to wheat
      production in Spain and has the potential to increase agronomic N-use efficiency
      on a long-term basis.

PMID- 25756863
TI  - An ultra-low power CMOS image sensor with on-chip energy harvesting and power
      management capability.
AB  - An ultra-low power CMOS image sensor with on-chip energy harvesting and power
      management capability is introduced in this paper. The photodiode pixel array can
      not only capture images but also harvest solar energy. As such, the CMOS image
      sensor chip is able to switch between imaging and harvesting modes towards self
      power operation. Moreover, an on-chip maximum power point tracking (MPPT)-based
      power management system (PMS) is designed for the dual-mode image sensor to
      further improve the energy efficiency. A new isolated P-well energy harvesting
      and imaging (EHI) pixel with very high fill factor is introduced. Several ultra
      low power design techniques such as reset and select boosting techniques have
      been utilized to maintain a wide pixel dynamic range. The chip was designed and
      fabricated in a 1.8 V, 1P6M 0.18 um CMOS process. Total power consumption of the
      imager is 6.53 uW for a 96 * 96 pixel array with 1 V supply and 5 fps frame rate.
      Up to 30 MUW of power could be generated by the new EHI pixels. The PMS is
      capable of providing 3* the power required during imaging mode with 50%
      efficiency allowing energy autonomous operation with a 72.5% duty cycle. 

PMID- 25756862
TI  - Design of a mobile brain computer interface-based smart multimedia controller.
AB  - Music is a way of expressing our feelings and emotions. Suitable music can
      positively affect people. However, current multimedia control methods, such as
      manual selection or automatic random mechanisms, which are now applied broadly in
      MP3 and CD players, cannot adaptively select suitable music according to the
      user's physiological state. In this study, a brain computer interface-based smart
      multimedia controller was proposed to select music in different situations
      according to the user's physiological state. Here, a commercial mobile tablet was
      used as the multimedia platform, and a wireless multi-channel
      electroencephalograph (EEG) acquisition module was designed for real-time EEG
      monitoring. A smart multimedia control program built in the multimedia platform
      was developed to analyze the user's EEG feature and select music according
      his/her state. The relationship between the user's state and music sorted by
      listener's preference was also examined in this study. The experimental results
      show that real-time music biofeedback according a user's EEG feature may
      positively improve the user's attention state. 

PMID- 25756864
TI  - SEnviro: a sensorized platform proposal using open hardware and open standards.
AB  - The need for constant monitoring of environmental conditions has produced an
      increase in the development of wireless sensor networks (WSN). The drive towards
      smart cities has produced the need for smart sensors to be able to monitor what
      is happening in our cities. This, combined with the decrease in hardware
      component prices and the increase in the popularity of open hardware, has favored
      the deployment of sensor networks based on open hardware. The new trends in
      Internet Protocol (IP) communication between sensor nodes allow sensor access via
      the Internet, turning them into smart objects (Internet of Things and Web of
      Things). Currently, WSNs provide data in different formats. There is a lack of
      communication protocol standardization, which turns into interoperability issues
      when connecting different sensor networks or even when connecting different
      sensor nodes within the same network. This work presents a sensorized platform
      proposal that adheres to the principles of the Internet of Things and theWeb of
      Things. Wireless sensor nodes were built using open hardware solutions, and
      communications rely on the HTTP/IP Internet protocols. The Open Geospatial
      Consortium (OGC) SensorThings API candidate standard was used as a neutral format
      to avoid interoperability issues. An environmental WSN developed following the
      proposed architecture was built as a proof of concept. Details on how to build
      each node and a study regarding energy concerns are presented. 

PMID- 25756865
TI  - Interstitial photoacoustic sensor for the measurement of tissue temperature
      during interstitial laser phototherapy.
AB  - Photothermal therapy is an effective means to induce tumor cell death, since
      tumor tissue is more sensitive to temperature increases than normal tissue.
      Biological responses depend on tissue temperature; target tissue temperature
      needs to be precisely measured and controlled to achieve desired thermal effects.
      In this work, a unique photoacoustic (PA) sensor is proposed for temperature
      measurement during interstitial laser phototherapy. A continuous-wave laser light
      and a pulsed laser light, for photothermal irradiation and photoacoustic
      temperature measurement, respectively, were delivered to the target tissue
      through a fiber coupler. During laser irradiation, the PA amplitude was measured.
      The Gruneisen parameter and the bioheat equation were used to determine the
      temperature in strategic positions in the target tissue. Our results demonstrate
      that the interstitial PA amplitude is a linear function of temperature in the
      range of 22 to 55  degrees C, as confirmed by thermocouple measurement.
      Furthermore, by choosing appropriate laser parameters, the maximum temperature
      surrounding the active diffuse fiber tip in tissue can be controlled in the range
      of 41 to 55  degrees C. Thus, this sensor could potentially be used for fast,
      accurate, and convenient three-dimensional temperature measurement, and for real
      time feedback and control of interstitial laser phototherapy in cancer treatment.

PMID- 25756866
TI  - Temperature-phase converter based on a LC cell as a variable capacitance.
AB  - The main characteristic of liquid crystals is that their properties, both
      electrical and optical, can be modified through a convenient applied signal, for
      instance a certain voltage. This tunable behavior of liquid crystals is directly
      related to the orientation of their nanometric components with respect to a
      director direction. However, the initial alignment is a fabrication-dependent
      parameter and may be either planar or homeotropic. In addition, the strong
      dependence of the properties of liquid crystals with the temperature is well
      known and widely used for several temperature sensors. This dependence is
      produced by the influence of the temperature on the ordering of the molecules. In
      this work, we have studied the temperature dependence of the electric properties
      of a liquid crystal cell, in particular the dielectric permittivity, with the
      temperature as a function of the initial alignment set during the fabrication
      process. Starting from experimental measurements, an equivalent circuit model
      including the temperature dependence has been proposed. We have observed that a
      good linearity in a wide temperature range is provided at a suitable exciting
      frequency. Finally, a proper conditioner circuit is proposed as a powerful tool
      for linear and high sensibility temperature measurement. 

PMID- 25756867
TI  - Quantifying efficacy and limits of unmanned aerial vehicle (UAV) technology for
      weed seedling detection as affected by sensor resolution.
AB  - In order to optimize the application of herbicides in weed-crop systems, accurate
      and timely weed maps of the crop-field are required. In this context, this
      investigation quantified the efficacy and limitations of remote images collected
      with an unmanned aerial vehicle (UAV) for early detection of weed seedlings. The
      ability to discriminate weeds was significantly affected by the imagery spectral
      (type of camera), spatial (flight altitude) and temporal (the date of the study)
      resolutions. The colour-infrared images captured at 40 m and 50 days after sowing
      (date 2), when plants had 5-6 true leaves, had the highest weed detection
      accuracy (up to 91%). At this flight altitude, the images captured before date 2
      had slightly better results than the images captured later. However, this trend
      changed in the visible-light images captured at 60 m and higher, which had
      notably better results on date 3 (57 days after sowing) because of the larger
      size of the weed plants. Our results showed the requirements on spectral and
      spatial resolutions needed to generate a suitable weed map early in the growing
      season, as well as the best moment for the UAV image acquisition, with the
      ultimate objective of applying site-specific weed management operations. 

PMID- 25756868
TI  - Spatial ability in radiologists: a necessary prerequisite?
AB  - Visuospatial ability is fundamental to the cognitive understanding of the three
      dimensional environment and is widely recognized as an important skill in the
      performance of challenging visuospatial tasks. Its contribution to attainment and
      performance in a variety of professional disciplines is recognized, but there is
      relatively little known in relation to its relevance in radiological practice. On
      the basis of a review of the existing cognitive psychological literature and on
      the basis of the author's own observations, and on the assumption that spatial
      ability is of increasing and fundamental importance to high-level performance as
      a radiologist, it is proposed that consideration should be given to the testing
      of visuospatial ability as part of the selection process for prospective
      applicants to radiology training programmes. 

PMID- 25756869
TI  - Threats to internal validity in exercise science: a review of overlooked
      confounding variables.
AB  - Internal validity refers to the degree of control exerted over potential
      confounding variables to reduce alternative explanations for the effects of
      various treatments. In exercise and sports-science research and routine testing,
      internal validity is commonly achieved by controlling variables such as exercise
      and warm-up protocols, prior training, nutritional intake before testing, ambient
      temperature, time of testing, hours of sleep, age, and gender. However, a number
      of other potential confounding variables often do not receive adequate attention
      in sports physiology and performance research. These confounding variables
      include instructions on how to perform the test, volume and frequency of verbal
      encouragement, knowledge of exercise endpoint, number and gender of observers in
      the room, influence of music played before and during testing, and the effects of
      mental fatigue on performance. In this review the authors discuss these variables
      in relation to common testing environments in exercise and sports science and
      present some recommendations with the goal of reducing possible threats to
      internal validity. 

PMID- 25756871
TI  - Wood-inhabiting beetles in low stumps, high stumps and logs on boreal clear-cuts:
      implications for dead wood management.
AB  - The increasing demand for biofuels from logging residues require serious
      attention on the importance of dead wood substrates on clear-cuts for the many
      forestry-intolerant saproxylic (wood-inhabiting) species. In particular, the
      emerging harvest of low stumps motivates further study of these substrates. On
      ten clear-cuts we compared the species richness, abundance and species
      composition of saproxylic beetles hatching from four to nine year old low stumps,
      high stumps and logs of Norway spruce. By using emergence traps we collected a
      total of 2,670 saproxylic beetles among 195 species during the summers of 2006,
      2007 and 2009. We found that the species assemblages differed significantly
      between high stumps and logs all three years. The species assemblages of low
      stumps, on the other hand, were intermediate to those found in logs and high
      stumps. There were also significant difference in species richness between the
      three examined years, and we found significant effect of substrate type on
      richness of predators and fungivores. As shown in previous studies of low stumps
      on clear-cuts they can sustain large numbers of different saproxylic beetles,
      including red-listed species. Our study does, in addition to this fact, highlight
      a possible problem in creating just one type of substrate as a tool for
      conservation in forestry. Species assemblages in high stumps did not differ
      significantly from those found in low stumps. Instead logs, which constitute a
      scarcer substrate type on clear-cuts, provided habitat for a more distinct
      assemblage of saproxylic species than high stumps. It can therefore be questioned
      whether high stumps are an optimal tool for nature conservation in clear-cutting
      forestry. Our results also indicate that low stumps constitute an equally
      important substrate as high stumps and logs, and we therefore suggest that stump
      harvesting is done after carefully evaluating measures to provide habitat for
      saproxylic organisms. 

PMID- 25756870
TI  - Variation in siderophore biosynthetic gene distribution and production across
      environmental and faecal populations of Escherichia coli.
AB  - Iron is essential for Escherichia coli growth and survival in the host and the
      external environment, but its availability is generally low due to the poor
      solubility of its ferric form in aqueous environments and the presence of iron
      withholding proteins in the host. Most E. coli can increase access to iron by
      excreting siderophores such as enterobactin, which have a very strong affinity
      for Fe3+. A smaller proportion of isolates can generate up to 3 additional
      siderophores linked with pathogenesis; aerobactin, salmochelin, and
      yersiniabactin. However, non-pathogenic E. coli are also able to synthesise these
      virulence-associated siderophores. This raises questions about their role in the
      ecology of E. coli, beyond virulence, and whether specific siderophores might be
      linked with persistence in the external environment. Under the assumption that
      selection favours phenotypes that confer a fitness advantage, we compared
      siderophore production and gene distribution in E. coli isolated either from
      agricultural plants or the faeces of healthy mammals. This population-level
      comparison has revealed that under iron limiting growth conditions plant
      associated isolates produced lower amounts of siderophores than faecal isolates.
      Additionally, multiplex PCR showed that environmental isolates were less likely
      to contain loci associated with aerobactin and yersiniabactin synthesis. Although
      aerobactin was linked with strong siderophore excretion, a significant difference
      in production was still observed between plant and faecal isolates when the
      analysis was restricted to strains only able to synthesise enterobactin. This
      finding suggests that the regulatory response to iron limitation may be an
      important trait associated with adaptation to the non-host environment. Our
      findings are consistent with the hypothesis that the ability to produce multiple
      siderophores facilitates E. coli gut colonisation and plays an important role in
      E. coli commensalism. 

PMID- 25756872
TI  - Microfluidics-based single cell analysis reveals drug-dependent motility changes
      in trypanosomes.
AB  - We present a single cell viability assay, based on chemical gradient
      microfluidics in combination with optical micromanipulation. Here, we used this
      combination to in situ monitor the effects of drugs and chemicals on the motility
      of the flagellated unicellular parasite Trypanosoma brucei; specifically, the
      local cell velocity and the mean squared displacement (MSD) of the cell
      trajectories. With our method, we are able to record in situ cell fixation by
      glutaraldehyde, and to quantify the critical concentration of 2-deoxy-d-glucose
      required to completely paralyze trypanosomes. In addition, we detected and
      quantified the impact on cell propulsion and energy generation at much lower 2
      deoxy-d-glucose concentrations. Our microfluidics-based approach advances fast
      cell-based drug testing in a way that allows us to distinguish cytocidal from
      cytostatic drug effects, screen effective dosages, and investigate the impact on
      cell motility of drugs and chemicals. Using suramin, we could reveal the impact
      of the widely used drug on trypanosomes: suramin lowers trypanosome motility and
      induces cell-lysis after endocytosis. 

PMID- 25756873
TI  - GM-CSF promotes migration of human monocytes across the blood brain barrier.
AB  - Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the
      central nervous system (CNS). Infiltration of monocytes into the CNS is crucial
      for disease onset and progression. Animal studies indicate that granulocyte
      macrophages colony-stimulating factor (GM-CSF) may play an essential role in this
      process, possibly by acting on the migratory capacities of myeloid cells across
      the blood-brain barrier. This study describes the effect of GM-CSF on human
      monocytes, macrophages, and microglia. Furthermore, the expression of GM-CSF and
      its receptor was investigated in the CNS under healthy and pathological
      conditions. We show that GM-CSF enhances monocyte migration across human blood
      brain barrier endothelial cells in vitro. Next, immunohistochemical analysis on
      human brain tissues revealed that GM-CSF is highly expressed by microglia and
      macrophages in MS lesions. The GM-CSF receptor is expressed by neurons in the rim
      of combined gray/white matter lesions and astrocytes. Finally, the effect of GM
      CSF on human macrophages was determined, revealing an intermediate activation
      status, with a phenotype similar to that observed in active MS lesions. Together
      our data indicate that GM-CSF is a powerful stimulator of monocyte migration, and
      is abundantly present in the inflamed CNS where it may act as an activator of
      macrophages and microglia. 

PMID- 25756876
TI  - Identification of genes associated with low furanocoumarin content in grapefruit.
AB  - Some furanocoumarins in grapefruit (Citrus paradisi) are associated with the so
      called grapefruit juice effect. Previous phytochemical quantification and genetic
      analysis suggested that the synthesis of these furanocoumarins may be controlled
      by a single gene in the pathway. In this study, cDNA-amplified fragment length
      polymorphism (cDNA-AFLP) analysis of fruit tissues was performed to identify the
      candidate gene(s) likely associated with low furanocoumarin content in
      grapefruit. Fifteen tentative differentially expressed fragments were cloned
      through the cDNA-AFLP analysis of the grapefruit variety Foster and its
      spontaneous low-furanocoumarin mutant Low Acid Foster. Sequence analysis revealed
      a cDNA-AFLP fragment, Contig 6, was homologous to a substrate-proved psoralen
      synthase gene, CYP71A22, and was part of citrus unigenes Cit.3003 and Csi.1332,
      and predicted genes Ciclev10004717m in mandarin and orange1.1g041507m in sweet
      orange. The two predicted genes contained the highly conserved motifs at one of
      the substrate recognition sites of CYP71A22. Digital gene expression profile
      showed the unigenes were expressed only in fruit and seed. Quantitative real-time
      PCR also proved Contig 6 was down-regulated in Low Acid Foster. These results
      showed the differentially expressed Contig 6 was related to the reduced
      furanocoumarin levels in the mutant. The identified fragment, homologs, unigenes,
      and genes may facilitate further furanocoumarin genetic study and grapefruit
      variety improvement. 

PMID- 25756875
TI  - The influence of familial predisposition to cardiovascular complications upon
      childhood obesity treatment.
AB  - INTRODUCTION: The aim was to investigate whether a familial predisposition to
      obesity related cardiovascular complications was associated with the degree of
      obesity at baseline and/or changes in the degree of obesity during a
      multidisciplinary childhood obesity treatment program. METHODS: The study
      included 1421 obese children (634 boys) with a median age of 11.5 years (range
      3.1-17.9 years), enrolled in treatment for 0.04 to 5.90 years (median 1.3 years)
      at the Children's Obesity Clinic, Denmark. At baseline, weight and height were
      measured, body mass index (BMI) standard deviation score (SDS) calculated, and
      self-reported information on familial predisposition to obesity, hypertension,
      type 2 diabetes mellitus (T2DM), thromboembolic events, and dyslipidaemia were
      obtained. A familial predisposition included events in biological parents,
      siblings, grandparents, uncles, and aunts. The treatment outcomes were
      categorically analysed according to the prevalence of familial predispositions.
      RESULTS: The median BMI SDS at enrollment was 3.2 in boys and 2.8 in girls. One
      thousand-and-forty-one children had obesity in their family, 773 had
      hypertension, 551 had T2DM, 568 had thromboembolic events, and 583 had
      dyslipidaemia. Altogether, 733 had three or more predispositions. At baseline,
      familial T2DM was associated with a higher mean BMI SDS (p = 0.03), but no
      associations were found between the other predispositions and the children's
      degree of obesity. During treatment, girls with familial obesity lost more
      weight, compared to girls without familial obesity (p = 0.04). No other familial
      predispositions were associated with changes in BMI SDS during treatment.
      CONCLUSION: Obese children with a familial predisposition to T2DM showed a
      significantly higher degree of obesity at baseline and girls with familial
      obesity responded better to treatment. Besides these findings, no other
      associations were found between the occurrence of familial predispositions and
      the degree of obesity or changes herein during multidisciplinary childhood
      obesity treatment.

PMID- 25756874
TI  - Exposure to Leishmania braziliensis triggers neutrophil activation and apoptosis.
AB  - BACKGROUND: Neutrophils are the first line of defense against invading pathogens
      and are rapidly recruited to the sites of Leishmania inoculation. During
      Leishmania braziliensis infection, depletion of inflammatory cells significantly
      increases the parasite load whereas co-inoculation of neutrophils plus L.
      braziliensis had an opposite effect. Moreover, the co-culture of infected
      macrophages and neutrophils also induced parasite killing leading us to ask how
      neutrophils alone respond to an L. braziliensis exposure. Herein we focused on
      understanding the interaction between neutrophils and L. braziliensis, exploring
      cell activation and apoptotic fate. METHODS AND FINDINGS: Inoculation of serum
      opsonized L. braziliensis promastigotes in mice induced neutrophil accumulation
      in vivo, peaking at 24 h. In vitro, exposure of thyoglycollate-elicited
      inflammatory or bone marrow neutrophils to L. braziliensis modulated the
      expression of surface molecules such as CD18 and CD62L, and induced the oxidative
      burst. Using mCherry-expressing L. braziliensis, we determined that such effects
      were mainly observed in infected and not in bystander cells. Neutrophil
      activation following contact with L. braziliensis was also confirmed by the
      release of TNF-alpha and neutrophil elastase. Lastly, neutrophils infected with
      L. braziliensis but not with L. major displayed markers of early apoptosis.
      CONCLUSIONS: We show that L. braziliensis induces neutrophil recruitment in vivo
      and that neutrophils exposed to the parasite in vitro respond through activation
      and release of inflammatory mediators. This outcome may impact on parasite
      elimination, particularly at the early stages of infection.

PMID- 25756878
TI  - Galactorrhea with normal prolactin levels associated with duloxetine.

PMID- 25756877
TI  - Reduced expression of CD27 by collagenase treatment: implications for
      interpreting b cell data in tissues.
AB  - Surface markers have been used to identify distinct cell subpopulations and to
      delineate various stages of maturation or activation of lymphocytes. In
      particular CD27 is used for delineation of naive and memory B cell populations,
      and is readily detected by flow cytometry. We here used flow cytometry to examine
      the expression of CD27 on lymphocytes isolated from various tissues of rhesus
      macaques, and found its expression was consistently low to absent on intestinal
      cell suspensions. However, immunohistochemistry revealed abundant CD27+ cells in
      intestinal tissue sections. Further investigation showed the marked loss of CD27
      expression on processed intestinal cells was due to collagenase digestion of
      intestinal tissues, yet CD27 expression was recoverable within hours of cell
      isolation. By combining confocal microscopy, we confirmed that only a fraction of
      B cells express CD27, in contrast to expression on all T cells from tissues
      examined including the gut. Taken together, our results suggest that CD27 may be
      a memory marker for B cells, but not for T cells, since essentially all CD3 T
      cells expressed CD27. In summary, it is important to consider the influence of
      isolation procedures on cell surface expression of phenotypic markers, especially
      when examining tissue-resident lymphocytes by flow cytometry. 

PMID- 25756879
TI  - Integrating peer perspectives into mental health services.

PMID- 25756881
TI  - Datapoints: psychiatrists' perceptions of insurance-related medication access
      barriers.

PMID- 25756882
TI  - Best Practices: MEDNET: a multistate policy maker-researcher collaboration to
      improve prescribing practices.
AB  - States face new federal requirements to monitor psychotropic prescribing
      practices for children and adults enrolled in Medicaid. Effective use of quality
      measurement and quality improvement strategies hold the promise of improved
      outcomes for public mental health systems. The Medicaid/Mental Health Network for
      Evidence-Based Treatment (MEDNET), funded by the Agency for Healthcare Research
      and Quality, is a multistate Medicaid quality collaborative with the Rutgers
      University Center for Health Services Research on Pharmacotherapy, Chronic
      Disease Management, and Outcomes. This column describes the development,
      infrastructure, challenges, and early evidence of success of this public-academic
      partnership, the first multistate Medicaid quality improvement collaborative to
      focus on psychotropic medications. 

PMID- 25756883
TI  - Family partners improve early childhood mental health services.

PMID- 25756884
TI  - Clean sweep: clients as role models to teach organizational skills.

PMID- 25756896
TI  - Clinical setting influences off-label and unlicensed prescribing in a paediatric
      teaching hospital.
AB  - PURPOSE: To estimate the prevalence of off-label and unlicensed prescribing
      during 2008 at a major paediatric teaching hospital in Western Australia.
      METHODS: A 12-month retrospective study was conducted at Princess Margaret
      Hospital using medication chart records randomly selected from 145,550 patient
      encounters from the Emergency Department, Inpatient Wards and Outpatient Clinics.
      Patient and prescribing data were collected. Drugs were classified as off-label
      or unlicensed based on Australian registration data. A hierarchical system of
      age, indication, route of administration and dosage was used. Drugs were
      classified according to the Anatomical Therapeutic Chemical Code. RESULTS: A
      total of 1,037 paediatric patients were selected where 2,654 prescriptions for
      330 different drugs were prescribed to 699 patients (67.4%). Most off-label drugs
      (n = 295; 43.3%) were from the nervous system; a majority of unlicensed drugs
      were systemic hormonal preparations excluding sex hormones (n = 22, 32.4%).
      Inpatients were prescribed more off-label drugs than outpatients or Emergency
      Department patients (p < 0.0001). Most off-label prescribing occurred in infants
      and children (31.7% and 35.9% respectively) and the highest percentage of
      unlicensed prescribing (7.2%) occurred in infants (p < 0.0001). There were 25.7%
      of off-label and 2.6% of unlicensed medications prescribed across all three
      settings. Common reasons for off-label prescribing were dosage (47.4%) and age
      (43.2%). CONCLUSION: This study confirmed off-label and unlicensed use of drugs
      remains common. Further, that prevalence of both is influenced by the clinical
      setting, which has implications in regards to medication misadventure, and the
      need to have systems in place to minimise medication errors. Further, there
      remains a need for changes in the regulatory system in Australia to ensure that
      manufacturers incorporate, as it becomes available, evidence regarding efficacy
      and safety of their drugs in children in the official product information.

PMID- 25756898
TI  - Larval fish feeding ecology, growth and mortality from two basins with
      contrasting environmental conditions of an inner sea of northern Patagonia,
      Chile.
AB  - During austral spring 2011, a survey was carried out in the inland sea (41
      degrees 30'-44 degrees S) of north Patagonia, South Pacific, studying a northern
      basin (NB: Reloncavi Fjord, Reloncavi Sound and Ancud Gulf) characterized by
      estuarine regime with stronger vertical stratification and warmer (11-14  degrees
      C) and most productive waters, and a southern basin (SB: Corcovado Gulf and Guafo
      mouth), with more oceanic water influence, showed mixed conditions of the water
      column, colder (11-10.5  degrees C) and less productive waters. Otolith
      microstructure and gut content analysis of larval lightfish Maurolicus
      parvipinnis and rockfish Sebastes oculatus were studied. Larval M. parvipinnis
      showed similar growth rates in both regions (0.13-0.15 mm d(-1)), but in NB
      larvae were larger-at-age than in SB. Larval S. oculatus showed no differences in
      size-at-age and larval growth (0.16 and 0.11 mm d(-1) for NB and SB,
      respectively). M. parvipinnis larvae from NB had larger number of prey items
      (mostly invertebrate eggs), similar total volume in their guts and smaller prey
      size than larvae collected in SB (mainly calanoid copepods). Larval S. oculatus
      had similar number, volume and body width of prey ingested at both basins,
      although prey ingestion rate by size was 5 times larger in NB than in SB, and
      prey composition varied from nauplii in NB to copepodites in SB. This study
      provides evidence that physical-biological interactions during larval stages of
      marine fishes from Chilean Patagonia are species-specific, and that in some cases
      large size-at-age correspond to increasing foraging success.

PMID- 25756897
TI  - Innate immune response to Streptococcus pyogenes depends on the combined
      activation of TLR13 and TLR2.
AB  - Innate immune recognition of the major human-specific Gram-positive pathogen
      Streptococcus pyogenes is not understood. Here we show that mice employ Toll-like
      receptor (TLR) 2- and TLR13-mediated recognition of S. pyogenes. These TLR
      pathways are non-redundant in the in vivo context of animal infection, but are
      largely redundant in vitro, as only inactivation of both of them abolishes
      inflammatory cytokine production by macrophages and dendritic cells infected with
      S. pyogenes. Mechanistically, S. pyogenes is initially recognized in a
      phagocytosis-independent manner by TLR2 and subsequently by TLR13 upon
      internalization. We show that the TLR13 response is specifically triggered by S.
      pyogenes rRNA and that Tlr13-/- cells respond to S. pyogenes infection solely by
      engagement of TLR2. TLR13 is absent from humans and, remarkably, we find no
      equivalent route for S. pyogenes RNA recognition in human macrophages.
      Phylogenetic analysis reveals that TLR13 occurs in all kingdoms but only in few
      mammals, including mice and rats, which are naturally resistant against S.
      pyogenes. Our study establishes that the dissimilar expression of TLR13 in mice
      and humans has functional consequences for recognition of S. pyogenes in these
      organisms. 

PMID- 25756899
TI  - The effects of water acidification, temperature and salinity on the regenerative
      capacity of the polychaete Diopatra neapolitana.
AB  - Changes in seawater pH, temperature and salinity are expected to occur in the
      near future, which can be a threat to aquatic systems, mainly for marine coastal
      areas, and their inhabiting species. Hence, the present study proposes to
      evaluate the effects of temperature shifts, pH decrease and salinity changes in
      the tissue's regenerative capacity of the polychaete Diopatra neapolitana. This
      study evidenced that D. neapolitana individuals exposed to lower pH exhibited a
      significantly lower capacity to regenerate their body, while with the increase of
      temperature individuals showed a higher capacity to regenerate their tissues.
      Furthermore, the present work demonstrated that individuals exposed to salinities
      28 and 35 did not present significant differences between them, while salinities
      21 and 42 negatively influenced the regenerative capacity of D. neapolitana. At
      the end of regeneration, comparing all conditions, high salinity (42) seemed to
      have a greater impact on the regenerative capacity of individuals than the other
      factors, since under this condition individuals took longer to completely
      regenerate. Overall, this study demonstrated that variations in abiotic factors
      can strongly affect D. neapolitana's performance. 

PMID- 25756900
TI  - Histopathological assessment of liver and gonad pathology in continental slope
      fish from the northeast Atlantic Ocean.
AB  - The deep-sea environment is a sink for a wide variety of contaminants including
      heavy metals and organic compounds of anthropogenic origin. Life history traits
      of many deep-water fish species including longevity and high trophic position may
      predispose them to contaminant exposure and subsequent induction of pathological
      changes, including tumour formation. The lack of evidence for this hypothesis
      prompted this investigation in order to provide data on the presence of
      pathological changes in the liver and gonads of several deep-water fish species.
      Fish were obtained from the north east region of the Bay of Biscay (north east
      Atlantic Ocean) by trawling at depths between 700 and 1400 m. Liver and gonad
      samples were collected on board ship and fixed for histological processing and
      subsequent examination by light microscopy. Hepatocellular and nuclear
      pleomorphism and individual cases of ovotestis and foci of cellular alteration
      (FCA) were detected in black scabbardfish (Aphanopus carbo). Six cases of FCA
      were observed in orange roughy (Hoplostethus atlanticus) (n = 50) together with a
      single case of hepatocellular adenoma. A wide variety of inflammatory and
      degenerative lesions were found in all species examined. Deep-water fish display
      a range of pathologies similar to those seen in shelf-sea species used for
      international monitoring programmes including biological effects of contaminants.
      This study has confirmed the utility of health screening in deep-water fish for
      detecting evidence of prior exposure to contaminants and has also gained evidence
      of pathology potentially associated with exposure to algal toxins.

PMID- 25756901
TI  - Clusterization modes of Ti on TiO2(1 1 0)-1 * 1 due to stablization by catalytic
      suboxide formation.
AB  - The electronic states of individual clusters formed from Ti deposition on a
      TiO(2)(1 1 0)-1 * 1 surface were measured using scanning tunneling spectroscopy
      (STS). The results of scanning tunneling microscopy (STM) suggests that as the
      amount of deposited Ti increased, at a critical height of 1.4 nm, the cluster
      growth changes from vertical oxide formation to lateral growth. Based on the STS
      spectra, the relation between the band-gap and cluster size was revealed. In the
      first oxide-formation mode, the band gaps decreased smoothly in response to the
      increase of the cluster size, while a band-gap-free (metallic) phase appears when
      the clusters are thicker than ~1.4 nm. This result indicates that Ti adatoms
      initially diffuse on the oxide surface and are stabilized by oxygen atoms from
      the substrate to form a suboxide interfacial layer. This catalytic suboxide
      formation promotes the vertical granular growth of the deposited Ti atoms.

PMID- 25756903
TI  - Systems biology of the secretory pathway: what have we learned so far?
AB  - Several RNAi screens were performed in search for regulators of the secretory
      pathway. These screens were performed in different organisms and cell lines and
      relied on different readouts. Therefore, they have only little overlap among
      their hits, leading to the question of what we have learned from this approach so
      far and how these screens contributed towards an integrative understanding of the
      endomembrane system. The aim of this review is to revisit these screens and
      discuss their strengths and weaknesses as well as potential reasons for their
      failure to overlap with each other. As with secretory trafficking, RNAi screens
      were also performed on other cellular processes such as cell migration and
      autophagy, both of which were shown to be intimately linked to secretion. Another
      aim of this review is to compare the outcome of the RNAi screens on secretion,
      autophagy and cell migration and ask whether the functional genomic approaches
      have uncovered potential mechanistic insights into the links between these
      processes. 

PMID- 25756905
TI  - Laparoscopic sleeve gastrectomy in five awake obese patients using paravertebral
      and superficial cervical plexus blockade.
AB  - We report laparoscopic sleeve gastrectomy in five awake obese patients, completed
      under regional anaesthesia provided by paravertebral and superficial cervical
      plexus blockade. The technique was acceptable to patients, surgeons and
      anaesthetists. 

PMID- 25756904
TI  - The ribosome biogenesis factor Nol11 is required for optimal rDNA transcription
      and craniofacial development in Xenopus.
AB  - The production of ribosomes is ubiquitous and fundamental to life. As such, it is
      surprising that defects in ribosome biogenesis underlie a growing number of
      symptomatically distinct inherited disorders, collectively called
      ribosomopathies. We previously determined that the nucleolar protein, NOL11, is
      essential for optimal pre-rRNA transcription and processing in human tissue
      culture cells. However, the role of NOL11 in the development of a multicellular
      organism remains unknown. Here, we reveal a critical function for NOL11 in
      vertebrate ribosome biogenesis and craniofacial development. Nol11 is strongly
      expressed in the developing cranial neural crest (CNC) of both amphibians and
      mammals, and knockdown of Xenopus nol11 results in impaired pre-rRNA
      transcription and processing, increased apoptosis, and abnormal development of
      the craniofacial cartilages. Inhibition of p53 rescues this skeletal phenotype,
      but not the underlying ribosome biogenesis defect, demonstrating an
      evolutionarily conserved control mechanism through which ribosome-impaired
      craniofacial cells are removed. Excessive activation of this mechanism impairs
      craniofacial development. Together, our findings reveal a novel requirement for
      Nol11 in craniofacial development, present the first frog model of a
      ribosomopathy, and provide further insight into the clinically important
      relationship between specific ribosome biogenesis proteins and craniofacial cell
      survival. 

PMID- 25756906
TI  - Improving proactive control with training on language switching in bilinguals.
AB  - The present study examined how a short period of language switching training
      affects nonverbal cognitive control, as measured by the AX version of the
      Continuous Performance Test. A group of Chinese-English bilinguals were trained
      over 10 days on a picture naming task that required switching between languages.
      We recorded their behavioral performance and event-related potentials before and
      after the training to examine its effects on cognitive performance. The
      behavioral measurement of proactive control, that is, goal maintenance before the
      occurrence of the target, is significantly larger in the post-training phase as
      compared with the pretraining phase, indicating a proactive control shift. The
      event-related potential results show that the training led to an increase in the
      mean amplitude of the N2 component, elicited by both the cue and the probe
      stimuli. A group of control participants who did not undergo training showed an
      enlarged N2 only for the probe but not for the cue stimuli in the second as
      compared with the first phase of testing. No variations in behavioral performance
      were found in the control group between the two phases of testing. These findings
      suggest that language switching training enhances proactive control in
      bilinguals. 

PMID- 25756907
TI  - Latency of modality-specific reactivation of auditory and visual information
      during episodic memory retrieval.
AB  - This study used magnetoencephalography (MEG) to examine the latency of modality
      specific reactivation in the visual and auditory cortices during a recognition
      task to determine the effects of reactivation on episodic memory retrieval. Nine
      right-handed healthy young adults participated in the experiment. The experiment
      consisted of a word-encoding phase and two recognition phases. Three encoding
      conditions were included: encoding words alone (word-only) and encoding words
      presented with either related pictures (visual) or related sounds (auditory). The
      recognition task was conducted in the MEG scanner 15 min after the completion of
      the encoding phase. After the recognition test, a source-recognition task was
      given, in which participants were required to choose whether each recognition
      word was not presented or was presented with which information during the
      encoding phase. Word recognition in the auditory condition was higher than that
      in the word-only condition. Confidence-of-recognition scores (d') and the source
      recognition test showed superior performance in both the visual and the auditory
      conditions compared with the word-only condition. An equivalent current dipoles
      analysis of MEG data indicated that higher equivalent current dipole amplitudes
      in the right fusiform gyrus occurred during the visual condition and in the
      superior temporal auditory cortices during the auditory condition, both 450-550
      ms after onset of the recognition stimuli. Results suggest that reactivation of
      visual and auditory brain regions during recognition binds language with modality
      specific information and that reactivation enhances confidence in one's
      recognition performance.

PMID- 25756909
TI  - Neurobasal medium toxicity on mature cortical neurons.
AB  - Neurobasal medium (NBM) is a widely used medium for neuronal cultures, originally
      formulated to support survival of rat hippocampal neurons, but then optimized for
      several other neuronal subtypes. In the present study, the toxic effect of NBM on
      long-term cortical neuron cultures has been reported and investigated. A
      significant neuronal cell loss was observed 24 h after the total medium change
      performed at days in vitro 10. The neurotoxic effect was specifically because of
      NBM-A, a commercially derived modification of classic NBM, as neurons exposed to
      minimum essential medium for 24 h did not show the same mortality rate. We showed
      that the toxic effect was mediated by the N-methyl-D-aspartate receptor (NMDAr)
      as its inactivation partly prevented NBM-induced neuronal loss, and the addition
      of NMDAr activators, such as L-cysteine or glycine to minimum essential medium,
      reproduced the same toxicity rate observed in NBM. Besides the toxicity
      associated with NMDAr activation, the decreased antioxidative defenses also
      worsen (because of glutathione depletion) neuronal death, thus amplifying the
      effect of excitotoxic amino acids. Indeed, glutathione supplementation by the
      addition of its precursor N-acetyl-cysteine resulted in an increase in neuronal
      survival that partially prevented NBM-A toxicity. These results evidenced, on the
      one hand, the unsuitability of NBM-A for long-term neuronal culture, and on the
      other, they highlight the importance of selection of more suitable culture
      conditions. 

PMID- 25756908
TI  - Schisandrin B protects PC12 cells against oxidative stress of neurodegenerative
      diseases.
AB  - Increasing evidence places Schisandrin B (Sch B) at an important position in
      nerve protection, indicating that Sch B might play a positive role in the therapy
      of neurodegenerative diseases. However, there is little information on it. Our
      studies showed that pretreatment with Sch B could reduce lactate dehydrogenase,
      malondialdehyde, and reactive oxygen species release and significantly increase
      the cell viability and the superoxide dismutase level. Sch B (10 MUM) markedly
      inhibited cell apoptosis, whereas LY294002 (20 MUM), a phosphatidylinositol-3
      kinase inhibitor, blocked the antiapoptotic effect. More importantly, Sch B (10
      MUM) increased the phosphoprotein kinase B/protein kinase B (Akt) and B-cell
      lymphoma-2/Bcl-2 associated X protein ratios on preincubation with cells for 2 h,
      which was then inhibited by LY294002 (20 MUM). Results indicate that Sch B can
      protect PC12 cells from apoptosis by activating the phosphatidylinositol-3
      kinase/Akt signaling pathway and may emerge as a potential drug for
      neurodegenerative diseases. 

PMID- 25756910
TI  - Does cellular sex matter? Dimorphic transcriptional differences between female
      and male endothelial cells.
AB  - OBJECTIVE: Significant sex differences exist in cardiovascular diseases. Although
      an impact of gonadal hormones is presumed, it is largely unknown whether sexually
      dimorphic gene expression also plays a role and whether cells themselves show
      intrinsic sex differences. METHODS: We performed whole genome expression analyses
      in human umbilical vein endothelial cells (HUVEC) from 20 male and 20 female
      donors and compared levels of gene transcription between the sexes. To further
      assess whether there is a sex-specific response to stress, we subjected male and
      female HUVEC to shear for 24 h and analysed changes in gene expression. RESULTS:
      Genes indicative for greater immune responsiveness were stronger expressed in
      female compared to male HUVEC. There was a significant enrichment of 77 immune
      related genes in female HUVEC. These increased transcriptional levels in female
      cells were verified for 20 genes by real-time RT-PCR. 6.7% of all mRNAs were
      regulated by shear stress. Female HUVEC showed a more pronounced transcriptional
      response to shear than did their male counterparts. In addition to quantitative
      differences, a number of genes were regulated in the opposite direction between
      the two sexes by shear stress. Functionally, female HUVEC showed a higher cell
      viability after serum starvation and an increased tube formation capacity
      compared to male cells. CONCLUSION: These findings underscore the importance for
      differentiation between male and female cells in cell culture experiments. This
      may apply not only to endothelial cells but might be generalized to other cell
      types as well. The observed sexual dimorphisms in gene expression in endothelial
      cells may contribute to sex differences between males and females in endothelial
      function.

PMID- 25756911
TI  - Interobserver Variability in the Measurement of Lower Leg Compartment Pressures.
AB  - OBJECTIVES: To determine whether interobserver technical variations and errors in
      the measurement of compartment pressures may affect measurement accuracy.
      METHODS: Four above-knee cadaveric specimens were used to create a consistent
      model of lower leg compartment syndrome. Thirty-eight physicians examined the
      limbs and measured 4 compartment pressures using the Intra-Compartmental Pressure
      Monitor (Stryker Orthopaedics). They were observed for correct assembly and use
      of the monitor. Measurements obtained were compared with known pressures.
      RESULTS: Of the total number of compartment measurements, 31% were made using the
      correct technique, 39% were made with lesser errors in technique, and 30% were
      made with catastrophic errors. Only 60% of measurements made with the correct
      technique were within 5 mm Hg of the standard pressure. Accuracy dropped to 42%
      for measurements taken with small errors in technique and 22% when a catastrophic
      error was committed. CONCLUSIONS: Variations in use of a commercially available
      pressure monitor exist, and errors are common. Proper use improved accuracy, but
      even with proper technique, 40% of the measurements were >5 mm Hg from the actual
      pressure. Based on our data, measurement accuracy with this device should be
      questioned and viewed within a range. Regular review and education of technique
      is strongly recommended.

PMID- 25756912
TI  - Outcomes After Intramedullary Nailing of Distal Tibial Fractures.
AB  - OBJECTIVES: To determine outcomes in the treatment of distal tibial fractures
      treated with intramedullary nails. DESIGN: Retrospective analysis. SETTING: Level
      I trauma center with follow-up in a private orthopaedic practice. MAIN OUTCOME
      MEASUREMENTS: Radiographic determination of alignment, nonunion, and malunion,
      clinical outcome (range of motion, and implant-associated complaints), wound
      complications, and fibular fixation. PATIENTS: A total of 105 patients with
      OTA/AO type A and C tibial fractures (<11 cm from the joint line) treated with
      intramedullary nailing. RESULTS: Distance of the fracture from the joint line
      averaged 6.1 cm (range, 0-11). Mean follow-up was 25.6 months (range, 12-74).
      Nonunion occurred in 20 (19%) fractures and were significantly associated with
      open fractures (P = 0.012), wound complications (P < 0.001), and the need for
      fibular fixation (P = 0.007). Sagittal plane alignment averaged 2.5 degrees (+/
      4.4) valgus. Malunion occurred in 25 (23.8%) fractures and again were
      significantly associated with open fractures (P = 0.045). Fifty (47.6%) patients
      had implant-related pain, which resolved in 27 (54.0%) after removal.
      CONCLUSIONS: Intramedullary nailing of distal tibial fractures is a suitable
      treatment option. Acceptable alignment and range of motion can be achieved. Both
      nonunions and malunions were significantly associated with open fractures, wound
      complications, and fibular fixation. Implant removal was needed in 25% of cases.
      LEVEL OF EVIDENCE: Therapeutic Level IV. See Instructions for Authors for a
      complete description of levels of evidence.

PMID- 25756913
TI  - Obesity Is Associated With More Complications and Longer Hospital Stays After
      Orthopaedic Trauma.
AB  - OBJECTIVE: The objective of this study was to characterize relationships between
      obesity and initial hospital stay, including complications, in patients with
      multiple system trauma and surgically treated fractures. DESIGN: Prospective,
      observational. SETTING: Level 1 trauma center. PATIENTS: Three hundred seventy
      six patients with an Injury Severity Score greater than 16 and mechanically
      unstable high-energy fractures of the femur, pelvic ring, acetabulum, or spine
      requiring stabilization. MAIN OUTCOME MEASUREMENTS: Data for obese (body mass
      index >= 30) versus nonobese patients included presence of pneumonia, deep vein
      thrombosis, pulmonary embolism, infection, organ failure, and mortality. Days in
      ICU and hospital, days on ventilator, transfusions, and surgical details were
      documented. RESULTS: Complications occurred more often in obese patients (38.0%
      vs. 28.4%, P = 0.03), with more acute renal failure (5.70% vs. 1.38%, P = 0.02)
      and infection (11.4% vs. 5.50%, P = 0.04). Days in ICU and mechanical ventilation
      times were longer for obese patients (7.06 vs. 5.25 days, P = 0.05 and 4.92 vs.
      2.90 days, P = 0.007, respectively). Mean total hospital stay was also longer for
      obese patients (12.3 vs. 9.79 days, P = 0.009). No significant differences in
      rates of mortality, multiple organ failure, or pulmonary complications were
      noted. Medically stable obese patients were almost twice as likely to experience
      delayed fracture fixation due to preference of the surgeon and were more likely
      to experience delay overall (26.0% vs. 16.1%; P = 0.02). Mean time from injury to
      fixation was 34.9 hours in obese patients versus 23.7 hours in nonobese patients
      (P = 0.03). CONCLUSIONS: Obesity was noted among 42% of our trauma patients. In
      obese patients, complications occurred more often and hospital and ICU stays were
      significantly longer. These increases are likely to be associated with greater
      hospital costs. Surgeon decision to delay procedures in medically stable obese
      patients may have contributed to these findings; definitive fixation was more
      likely to be delayed in obese patients. Further study to optimize the care of
      patients with increased body mass index may help to improve outcomes and minimize
      additional treatment expenses.

PMID- 25756914
TI  - Cost-Effectiveness of Diagnostic Strategies for Suspected Scaphoid Fractures.
AB  - OBJECTIVES: The aim of this study was to assess the cost effectiveness of
      multiple competing diagnostic strategies for suspected scaphoid fractures.
      METHODS: With published data, the authors created a decision-tree model
      simulating the diagnosis of suspected scaphoid fractures. Clinical outcomes,
      costs, and cost effectiveness of immediate computed tomography (CT), day 3
      magnetic resonance imaging (MRI), day 3 bone scan, week 2 radiographs alone, week
      2 radiographs-CT, week 2 radiographs-MRI, week 2 radiographs-bone scan, and
      immediate MRI were evaluated. The primary clinical outcome was the detection of
      scaphoid fractures. The authors adopted societal perspective, including both the
      costs of healthcare and the cost of lost productivity. The incremental cost
      effectiveness ratio (ICER), which expresses the incremental cost per incremental
      scaphoid fracture detected using a strategy, was calculated to compare these
      diagnostic strategies. Base case analysis, 1-way sensitivity analyses, and "worst
      case scenario" and "best case scenario" sensitivity analyses were performed.
      RESULTS: In the base case, the average cost per scaphoid fracture detected with
      immediate CT was $2553. The ICER of immediate MRI and day 3 MRI compared with
      immediate CT was $7483 and $32,000 per scaphoid fracture detected, respectively.
      The ICER of week 2 radiographs-MRI was around $170,000. Day 3 bone scan, week 2
      radiographs alone, week 2 radiographs-CT, and week 2 radiographs-bone scan
      strategy were dominated or extendedly dominated by MRI strategies. The results
      were generally robust in multiple sensitivity analyses. CONCLUSIONS: Immediate CT
      and MRI were the most cost-effective strategies for diagnosing suspected scaphoid
      fractures. LEVEL OF EVIDENCE: Economic and Decision Analyses Level II. See
      Instructions for Authors for a complete description of levels of evidence.

PMID- 25756915
TI  - Humane Surgical Positioning During Minor Limb Surgeries Under Local Anesthesia in
      Young Children.
AB  - Injured children are in pain, anxious, scared, and intimidated by the emergency
      room environment and parents often compound this anxiety by their own fears.
      During minor surgical procedures, a child held in the "humane position" by the
      parent is helpful. The child is positioned on the parent's lap so that the
      affected extremity is drawn out and placed on the side of the parent. The surgeon
      and instruments are positioned behind the parent's back out of the child's and
      parent's field of vision especially if the wound is bleeding actively. Physical
      intimacy with the parent is capitalized upon; this makes the child feel secure,
      comfortable, relaxed, and reassured during the procedure. 

PMID- 25756916
TI  - Predisposing Effect of Elbow Alignment on the Elbow Fracture Type in Children.
AB  - OBJECTIVES: Under the hypothesis that the elbow alignment, namely the carrying
      angle, could predispose individuals to a specific type of pediatric elbow
      fracture after a fall onto an outstretched arm, we investigated the relationship
      between radiographic carrying angle and elbow fracture type in children. DESIGN:
      Retrospective case-control study. SETTING: Level I pediatric trauma center.
      PATIENTS/PARTICIPANTS: We reviewed 374 children who were diagnosed with
      supracondylar fracture (SCF, n = 208), lateral condylar fracture (LCF, n = 132),
      and radial neck fracture (RNF, n = 34). INTERVENTION: The association between the
      radiographic carrying angle and the fracture type was investigated. MAIN OUTCOME
      MEASUREMENTS: To adjust for bias, 2 statistical methods were used: multivariate
      analysis using a baseline-category logistic model and a case-matching method
      using propensity score analysis. RESULTS: In the multivariate analysis, with SCF
      patients set as the baseline category, a more valgus-deviated elbow (increased
      carrying angle, P = 0.011) predisposed individuals to RNF, whereas a more varus
      deviated elbow (decreased carrying angle, P < 0.001) predisposed them to LCF. In
      the case-matched analysis, there were also significant differences in carrying
      angles between RNF and case-matched SCF patients (14.3 vs. 11.4 degrees, P =
      0.013) and between LCF and case-matched SCF patients (7.7 vs. 11.7 degrees, P <
      0.001). CONCLUSIONS: Elbow alignment, which may influence the transmission of
      traumatic force during a fall onto an outstretched elbow, could be a predisposing
      factor for specific types of pediatric elbow fracture. The results provide the
      additional information about the injury mechanisms of pediatric elbow fracture
      and may deepen our understanding of the fractures. LEVEL OF EVIDENCE: Prognostic
      Level III. See Instructions for Authors for a complete description of levels of
      evidence.

PMID- 25756918
TI  - Fixator-Assisted Femoral Lengthening Following Intramedullary Exchange Nailing
      for Subtrochanteric Non-union.
AB  - Non-unions in the femur can be a severely debilitating condition. When a non
      union results in significant shortening and leg length discrepancy, simple
      activities of daily living become extremely difficult and painful tasks. Here, we
      present a 36 year-old male who presented three years following a motor vehicle
      accident, complaining of severe left thigh pain and a short left lower extremity.
      Initially treated in Egypt with an intramedullary nail (IMN) and distal screws,
      work-up revealed an aseptic subtrochanteric femoral nonunion with a leg length
      discrepancy of approximately 6.5 cm. The patient subsequently underwent exchange
      nail with rail fixator placement and was lengthened over the nail. After
      achieving adequate length, the patient underwent a second exchange nail, which
      was complicated by IMN instability. Due to the IMN instability, the patient
      underwent a third exchange nail with blocking screws, and finally healed. On
      final follow-up, the patient was pain free and no longer felt the leg length
      discrepancy, with an overall discrepancy of approximately 1.5 cm.

PMID- 25756917
TI  - Does Ankle Aspiration for Acute Ankle Fractures Result in Pain Relief? A
      Prospective Randomized Double-Blinded Placebo Controlled Trial.
AB  - OBJECTIVES: Does ankle aspiration help with pain control in patients with ankle
      fractures? DESIGN: Prospective, double-blind, randomized, placebo-controlled
      trial. SETTING: Level 1 Academic Medical Center. PATIENTS/PARTICIPANTS:
      Consecutive skeletally mature patients with ankle fractures. INTERVENTION:
      Randomized between ankle aspiration and sham procedure. MAIN OUTCOME
      MEASUREMENTS: Pain scores for 72 hours after injury and pain medicine usage.
      RESULTS: Comparison between study subjects receiving ankle aspiration and sham
      procedure showed no significant differences in pain scores acutely in the
      emergency department or within 3 days after injury. There were also no
      statistically significant differences in pain medicine usage within 3 days after
      injury. Secondary outcomes, including lower leg volume, 6-month functional
      outcome scores, and complication rate, also showed no significant differences
      between subjects receiving aspiration and the sham procedure. CONCLUSIONS:
      Aspiration of acute ankle fractures does not result in decreased pain scores or
      opioid usage after aspiration. Aspiration of acute ankle fractures does not
      provide measurable clinical benefit. LEVEL OF EVIDENCE: Therapeutic Level I. See
      Instructions for Authors for a complete description of levels of evidence.

PMID- 25756919
TI  - Transcriptomic screening for cyclotides and other cysteine-rich proteins in the
      metallophyte Viola baoshanensis.
AB  - Cysteine (Cys)-rich proteins (CRPs) are frequently associated with plant defense
      and stress resistance. Viola baoshanensis is a cadmium (Cd) hyper-accumulating
      plant whose CRPs-based defense systems are so far poorly understood. Next
      generation sequencing (NGS) techniques and a specialist searching tool, CrpExcel,
      were employed for identifying CRPs in V. baoshanensis. The transcriptome
      sequences of V. baoshanensis were assembled primarily from 454FLX/Hiseq2000 reads
      of plant cDNA sequencing libraries. CrpExcel was then used to search the ORFs and
      9687 CRPs were identified, and included zinc finger (ZF) proteins, lipid transfer
      proteins, thaumatins and cyclotide precursors. Real-time PCR results showed that
      all CRP genes tested are constitutively expressed, but the genes of defensive
      peptides showed greater up-regulated expression than those of ZF-proteins in Cd-
      and/or wounding (Wd) treatments of V. baoshanensis seedlings. The NGS-derived
      sequences of cyclotide precursor genes were verified by RT-PCR and ABI3730
      sequencing studies, and 32 novel cyclotides were identified in V. baoshanensis.
      In general, the metal-binding sites of ZF-containing CRPs also represented the
      potential vulnerable targets of toxic metals. This study provides broad insights
      into CRPs-based defense systems and stress-vulnerable targets in V. baoshanensis.
      It now brings the number of cyclotide sequences in V. baoshanensis to 53 and
      based on projections from this work, the number of cyclotides in the Violaceae is
      now conservatively estimated to be >30000. 

PMID- 25756920
TI  - Biobased monoliths for adenovirus purification.
AB  - Adenoviruses are important platforms for vaccine development and vectors for gene
      therapy, increasing the demand for high titers of purified viral preparations.
      Monoliths are macroporous supports regarded as ideal for the purification of
      macromolecular complexes, including viral particles. Although common monoliths
      are based on synthetic polymers as methacrylates, we explored the potential of
      biopolymers processed by clean technologies to produce monoliths for adenovirus
      purification. Such an approach enables the development of disposable and
      biodegradable matrices for bioprocessing. A total of 20 monoliths were produced
      from different biopolymers (chitosan, agarose, and dextran), employing two
      distinct temperatures during the freezing process (-20  degrees C and -80 
      degrees C). The morphological and physical properties of the structures were
      thoroughly characterized. The monoliths presenting higher robustness and
      permeability rates were further analyzed for the nonspecific binding of
      Adenovirus serotype 5 (Ad5) preparations. The matrices presenting lower
      nonspecific Ad5 binding were further functionalized with quaternary amine anion
      exchange ligand glycidyltrimethylammonium chloride hydrochloride by two distinct
      methods, and their performance toward Ad5 purification was assessed. The monolith
      composed of chitosan and poly(vinyl) alcohol (50:50) prepared at -80  degrees C
      allowed 100% recovery of Ad5 particles bound to the support. This is the first
      report of the successful purification of adenovirus using monoliths obtained from
      biopolymers processed by clean technologies. 

PMID- 25756922
TI  - Correction to "Analyzing the first drafts of the human proteome".

PMID- 25756921
TI  - Bioinspired total synthesis and structural revision of yuremamine, an alkaloid
      from the entheogenic plant Mimosa tenuiflora.
AB  - Guided by a biosynthetic hypothesis, a serendipitous total synthesis of
      yuremamine has resulted in its structural revision from the putative
      pyrroloindole (1) to the flavonoidal indole (2), which was initially proposed as
      a biosynthetic intermediate.

PMID- 25756923
TI  - Novel Outer Retinal Optical Coherence Tomography Hyperreflective Abnormality
      Associated With Sub-Internal Limiting Membrane Hemorrhage.

PMID- 25756924
TI  - Spectral Domain Optical Coherence Tomography Reveals Hidden Fovea Beneath
      Extensive Vitreous Seeding From Retinoblastoma.

PMID- 25756925
TI  - [Is the association between mental disorders and sickness absence independent of
      sociodemographic factors?].
AB  - AIM: Mental diseases are highly prevalent and of increasing meaning for
      absenteeism. The association of absenteeism with vertical and horizontal
      dimensions of socioeconomic status is well-known. Against this background we
      investigated the independent association between mental diseases and absenteeism
      or long-time absenteeism of socioeconomic aspects. MATERIAL AND METHODS: Basis of
      this nationwide exploratory survey were the 6 339 employees born in 1959 or 1965
      and subject to statutory health insurance of the first wave of the lidA-cohort
      study 2011. The stepwise logistic regression analysis was used for the
      investigation of the effects of mental diseases on absenteeism or long-term
      absenteeism after adjustment for education, occupational position, income,
      gender, age, working-time and -stress. RESULTS: After adjustment for
      socioeconomic factors highly significant associations between mental diseases and
      absenteeism or even more long-term absenteeism were observed. These associations
      stayed significant after additional adjustment for work-related factors.
      CONCLUSION: Mental diseases were independent of sociodemographic factors and work
      related factors (working-time and -stress) associated with absenteeism or with
      long-term absenteeism. Unspecific programmes for the prevention and
      rehabilitation of mental diseases may contribute to the reduction of absenteeism.
      Apart from that causes of absenteeism in highly affected socioeconomic groups
      should be investigated.

PMID- 25756926
TI  - [Data linkage - respondents consent without selectivity?].
AB  - OBJECTIVE: The lidA Study is designed as a longitudinal survey. The respondent's
      consent is mandatory for storing sample data. Moreover, the survey data shall be
      linked with social security data of the Federal Employment Agency and
      individual's health insurance claims data in case of the respondent's written
      consent. This essay pursues the issue of whether this methodologically
      challenging objective of obtaining 3 consents within one study could be met
      without any selectivity. METHODOLOGY: The data basis is a cohort study with 2
      cohorts of a representative sample of employed individuals subject to social
      security contributions. The sample was interviewed for the first time in 2011.
      The analysis dataset comprises 6 585 respondents. RESULTS: Selectivity analyses
      prove that the realisation of the first measurement's sample turned out to be
      representative as well as unbiased. As expected, more respondents stated their
      willingness to remain in the panel and also consented to linkage of social
      security data than those who consented to linkage of health insurance claims
      data. All 3 consents were given without resulting in any bias. Even linking all 3
      consents does result in minimal effects of a few subgroups only. CONCLUSION: A
      significant number of respondents can be motivated to participate due to proper
      placement of the questions concerning consent and the provision of insight into
      the use of the data.

PMID- 25756927
TI  - Jordanian mothers' knowledge of infants' childrearing and developmental
      milestones.
AB  - AIM: This study explored Jordanian mothers' knowledge of infants' childrearing
      practices and developmental milestones, the socio-demographic variables of
      relevance to knowledge, and sources of information that guide childrearing
      practices. BACKGROUND: Parents' knowledge is considered the frame of reference
      for parents' interpretations of their children's behaviors and provides the basis
      for having the appropriate expectation of the child's developmental stage.
      Parents' knowledge of childrearing is essential for children's physical,
      cognitive and emotional development. METHODS: A cross-sectional design using a
      modified version of MacPhee's 'Knowledge of Infant Development Inventory' was
      used to assess 400 mothers' knowledge of infants' childrearing and developmental
      milestones, in Amman, Jordan. RESULTS: Mothers were found to be more
      knowledgeable in physical and safety skills and less in cognitive, emotional, and
      parent-infant interaction skills. Parental age, education, parity and planned
      pregnancy had limited influence on developmental milestones knowledge. Formal and
      informal sources of information were used conforming to traditional societies.
      DISCUSSION AND CONCLUSION: Results were congruent with findings from other
      studies in the region and similar traditional societies. Results allude to
      conclusion that mothers resort to informal sources and traditional practices to
      replace formally structured programmes when absent. IMPLICATIONS FOR NURSING AND
      HEALTH POLICY: Healthcare professionals, nursing schools and healthcare policy
      makers are encouraged to develop and institute a holistic approach encompassing
      physical, cognitive, emotional and parent-infant interaction domains in
      childrearing educational programmes. Structured parenting programmes for mothers
      and culturally accepted sources of information for fathers are essential to
      enhance parenting skills among Jordanian couples.

PMID- 25756929
TI  - Introgression of leginsulin, a cysteine-rich protein, and high-protein trait from
      an Asian soybean plant introduction genotype into a North American experimental
      soybean line.
AB  - Soybean is an important protein source for both humans and animals. However,
      soybean proteins are relatively poor in the sulfur-containing amino acids,
      cysteine and methionine. Improving the content of endogenous proteins rich in
      sulfur-containing amino acids could enhance the nutritive value of soybean meal.
      Leginsulin, a cysteine-rich peptide, predominantly accumulates in Asian soybean
      accessions but not in most North American cultivars. By screening diverse soybean
      accessions from the USDA Soybean Germplasm Collection, we were able to identify
      one plant introduction, PI 427138, as a high-protein line with relatively high
      amounts of both elemental sulfur and leginsulin. We introgressed these desirable
      traits from PI 427138 into an experimental line with the aim of improving the
      overall protein content and quality of seed proteins. Biochemical
      characterization of inbred progenies from the cross of LD00-3309 with PI 427138
      grown at six locations revealed stable ingression of high protein, high elemental
      sulfur, and high leginsulin accumulation. Comparison of soybean seed proteins
      resolved by high-resolution 2-D gel electrophoresis in combination with Delta2D
      image analysis software revealed preferential accumulation of a few glycinin
      subunits contributed to the increased protein content in the introgressed lines.
      Amino acid analysis revealed that even though the leginsulin introgressed lines
      had higher protein, leginsulin, and elemental sulfur, the overall concentration
      of sulfur-containing amino acids was not significantly altered when compared with
      the parental lines. The experimental soybean lines developed during this study
      (Leg-3, Leg-7, and Leg-8) lack A5, A4, and B3 glycinin subunits and could be
      utilized in breeding programs to develop high-quality tofu cultivars. 

PMID- 25756930
TI  - Reversibly cross-linked polyplexes enable cancer-targeted gene delivery via self
      promoted DNA release and self-diminished toxicity.
AB  - Polycations often suffer from the irreconcilable inconsistency between
      transfection efficiency and toxicity. Polymers with high molecular weight (MW)
      and cationic charge feature potent gene delivery capabilities, while in the
      meantime suffer from strong chemotoxicity, restricted intracellular DNA release,
      and low stability in vivo. To address these critical challenges, we herein
      developed pH-responsive, reversibly cross-linked, polyetheleneimine (PEI)-based
      polyplexes coated with hyaluronic acid (HA) for the effective and targeted gene
      delivery to cancer cells. Low-MW PEI was cross-linked with the ketal-containing
      linker, and the obtained high-MW analogue afforded potent gene delivery
      capabilities during transfection, while rapidly degraded into low-MW segments
      upon acid treatment in the endosomes, which promoted intracellular DNA release
      and reduced material toxicity. HA coating of the polyplexes shielded the surface
      positive charges to enhance their stability under physiological condition and
      simultaneously reduced the toxicity. Additionally, HA coating allowed active
      targeting to cancer cells to potentiate the transfection efficiencies in cancer
      cells in vitro and in vivo. This study therefore provides an effective approach
      to overcome the efficiency-toxicity inconsistence of nonviral vectors, which
      contributes insights into the design strategy of effective and safe vectors for
      cancer gene therapy. 

PMID- 25756931
TI  - Platinum multicubes prepared by ni(2+) -mediated shape evolution exhibit high
      electrocatalytic activity for oxygen reduction.
AB  - Pt(100) facets are generally considered less active for the oxygen reduction
      reaction (ORR). Reported herein is a unique Pt-branched structure, a multicube,
      whose surface is mostly enclosed by {100} facets but contains high-index facets
      at the small junction area between the adjacent cubic components. The synthesis
      is accomplished by a Ni(2+) -mediated facet evolution from high-index {311} to
      {100} facets on the frameworks of multipods. Despite the high {100} facet
      coverage, the Pt multicubes exhibit impressive ORR activity in terms of half-wave
      potential and current density nearly to the level of the most active Pt-based
      catalysts, while the durability of catalysts is well retained. The facet
      evolution creates a set of samples with tunable ratios of high-index to low-index
      facets. The results reveal that the excellent ORR performance of Pt multicubes is
      a combined result of active sites by high-index facets and low resistance by flat
      surface. It is anticipated that this work will offer a new approach to facet
      controlled synthesis and ORR catalysts design. 

PMID- 25756928
TI  - Role of PD-1 co-inhibitory pathway in HIV infection and potential therapeutic
      options.
AB  - Virus-specific CD8+ T cells play an important role in controlling viral
      infections including human immunodeficiency virus (HIV) infection. However,
      during chronic HIV infection, virus-specific CD8+ T cells undergo functional
      exhaustion, lose effector functions and fail to control viral infection. HIV
      specific CD8 T cells expressing high levels of co-inhibitory molecule programmed
      death-1 (PD-1) during the chronic infection and are characterized by lower
      proliferation, cytokine production, and cytotoxic abilities. Although,
      antiretroviral therapy has resulted in dramatic decline in HIV replication, there
      is no effective treatment currently available to eradicate viral reservoirs or
      restore virus-specific T or B-cell functions that may complement ART in order to
      eliminate the virus. In recent years, studies in mice and non-human primate
      models of HIV infection demonstrated the functional exhaustion of virus-specific
      T and B cells could be reversed by blockade of interaction between PD-1 and its
      cognate ligands (PD-L1 and PD-L2). In this review, we discuss recent advances in
      our understanding of PD-1 pathway in HIV/SIV infection and discuss the beneficial
      effects of PD-1 blockade during chronic HIV/SIV infection and its potential role
      as immunotherapy for HIV/AIDS. 

PMID- 25756932
TI  - Case of knee pain in a child: Intra-neural ganglion of the tibial nerve.

PMID- 25756933
TI  - An expert panel-based study on recognition of gastro-esophageal reflux in
      difficult esophageal pH-impedance tracings.
AB  - BACKGROUND: Despite existing criteria for scoring gastro-esophageal reflux (GER)
      in esophageal multichannel pH-impedance measurement (pH-I) tracings, inter- and
      intra-rater variability is large and agreement with automated analysis is poor.
      To identify parameters of difficult to analyze pH-I patterns and combine these
      into a statistical model that can identify GER episodes with an international
      consensus as gold standard. METHODS: Twenty-one experts from 10 countries were
      asked to mark GER presence for adult and pediatric pH-I patterns in an online pre
      assessment. During a consensus meeting, experts voted on patterns not reaching
      majority consensus (>70% agreement). Agreement was calculated between raters,
      between consensus and individual raters, and between consensus and software
      generated automated analysis. With eight selected parameters, multiple logistic
      regression analysis was performed to describe an algorithm sensitive and specific
      for detection of GER. KEY RESULTS: Majority consensus was reached for 35/79
      episodes in the online pre-assessment (interrater kappa = 0.332). Mean agreement
      between pre-assessment scores and final consensus was moderate (kappa = 0.466).
      Combining eight pH-I parameters did not result in a statistically significant
      model able to identify presence of GER. Recognizing a pattern as retrograde is
      the best indicator of GER, with 100% sensitivity and 81% specificity with expert
      consensus as gold standard. CONCLUSIONS & INFERENCES: Agreement between experts
      scoring difficult impedance patterns for presence or absence of GER is poor.
      Combining several characteristics into a statistical model did not improve
      diagnostic accuracy. Only the parameter 'retrograde propagation pattern' is an
      indicator of GER in difficult pH-I patterns.

PMID- 25756934
TI  - Epidemiology of chronic fungal rhinosinusitis in rural India.
AB  - A descriptive epidemiological study of fungal rhinosinusitis (FRS) was conducted
      in rural north India in the form of house-to-house survey of villages of two
      districts each of Punjab and Haryana provinces using a clinical case definition
      of chronic rhinosinusitis (CRS). The suspected cases were investigated further in
      the laboratory to confirm FRS. Air and environment were sampled in different
      seasons to find Aspergillus spore count. The prevalence of chronic FRS cases was
      at 0.11% of the population and Aspergillus flavus was the predominant (97.6%)
      agent of all types of chronic FRS. The chronic FRS patients were classified as
      allergic FRS 41 (56.1%), chronic granulomatous FRS 13 (17.8%), eosinophilic FRS
      11 (15.0%), fungal ball 7 (9.5%) and chronic invasive FRS 1 (1.3%). Aspergillus
      spores were present in large numbers (~20%) in air with significantly higher
      counts of A. flavus during winter months in the wheat-thrashing areas of Punjab
      as compared to Haryana (P = 0.0079). The present study identified high prevalence
      (27.5% of CRS cases) of chronic FRS cases in rural north India and its possible
      association with wheat harvesting seasons.

PMID- 25756935
TI  - Unadjusted Plasma Renin Activity as a "First-Look" Test to Decide Upon Further
      Investigations for Primary Aldosteronism.
AB  - The authors sought to define the 95th percentile of plasma renin activity (PRA)
      in a sample of patients with confirmed primary aldosteronism (PA) prior to
      adjustment of medications as a practical "first-look" test to identify those with
      very low ultimate likelihood of having PA. The aldosterone to renin ratio (ARR)
      was measured without adjustment of antihypertensive medications, with further
      workup as appropriate. Two groups were defined: patients with surgically
      "confirmed PA" (n=58) and patients with "high-probability PA" (n=59), defined as
      having any of the following: computed tomography-confirmed adrenal adenoma plus
      lateralizing adrenal vein sampling (AVS) without surgery, high ARR and
      hypokalemia but nonlateralizing AVS, or ARR more than four times the upper limit
      of normal. The PRA 95th percentile was 1.0 ng/mL/h. All outliers had hypokalemia
      and two had adrenal adenomas. There was no difference between the confirmed and
      high probability groups. In the absence of highly suspicious clinical features,
      patients with unadjusted PRA >1.0 ng/mL/h do not warrant further investigation
      for PA.

PMID- 25756936
TI  - Hemodynamic comparison between Trifecta and freestyle aortic valve during
      exercise in patients with small aortic root.
AB  - BACKGROUND: Patients with a small aortic annulus, that is <= 23 mm, constitute a
      challenge for the surgeon, because they are at high risk of patient-prosthesis
      mismatch. Stentless valves provide better hemodynamic performance at rest and
      during exercise than stented valves, and are advocated in this group of patients.
      A new-generation stented valve, the Trifecta (St. Jude), has recently become
      available with improved hemodynamics. The aim of this study was to compare the
      hemodynamic performance of Freestyle (Medtronic) and Trifecta at rest and during
      exercise in patients with a small aortic annulus. METHODS: From September 2012 to
      September 2014, 22 patients with a native aortic annulus <= 23 mm underwent
      ergometric stress testing one year after aortic valve replacement with either a
      Trifecta (12 patients) or a Freestyle (10 patients) bioprosthesis as part of a
      randomized study. RESULTS: The mean gradient at rest was 6.0 +/- 2.3 mmHg for
      Trifecta and 4.3 +/- 3.5 for Freestyle (p = 0.213). The mean gradient at peak of
      exercise was 9.7 +/- 3.4 mmHg for Trifecta and 7.4 +/- 5 mmHg for Freestyle (p =
      0.243). No significant differences were found between the two prostheses
      regarding other hemodynamic parameters: effective orifice area, velocity index,
      and performance indexes. CONCLUSION: Both the stented Trifecta and stentless
      Freestyle prostheses provide excellent hemodynamic results during physical stress
      in patients with a small aortic annulus. Our study confirms that Trifecta
      implantation results in low gradients at rest and during exercise and that the
      performance of Trifecta is similar to that of a stentless valve.

PMID- 25756937
TI  - Host-guest behavior of a heavy-atom heterocycle Re4(CO)16(MU-SbPh2)2(MU-H)2
      obtained from a palladium-assisted ring opening dimerization of Re2(CO)8(MU
      SbPh2)(MU-H).
AB  - The heavy-atom heterocycle Pd[Re2(CO)8(MU-SbPh2)(MU-H)]2 (5) has been synthesized
      by the palladium-catalyzed ring-opening cyclodimerization of the three-membered
      heterocycle Re2(CO)8(MU-SbPh2)(MU-H) (3). The Pd atom occupies the center of the
      ring. The Pd atom in 5 can be removed reversibly to yield the palladium-free
      heterocycle [Re2(CO)8((MU-SbPh2)(MU-H)]2 (6). 

PMID- 25756938
TI  - Age differences in working memory updating: the role of interference, focus
      switching and substituting information.
AB  - Working memory updating (WMU) tasks require different elements in working memory
      (WM) to be maintained simultaneously, accessing one of these elements, and
      substituting its content. This study examined possible developmental changes from
      childhood to adulthood both in focus switching and substituting information in
      WM. In addition, possible age-related changes in interference due to
      representational overlap between the different elements simultaneously held in
      these tasks were examined. Children (8- and 11-year-olds), adolescents (14-year
      olds) and younger adults (mean age=22 years) were administered a numerical
      updating memory task, in which updating and focus switching were manipulated. As
      expected, response times decreased and recall performance increased with age.
      More importantly, the time needed for focus switching was longer in children than
      in adolescents and younger adults. On the other hand, substitution of information
      and interference due to representational overlap were not affected by age. These
      results suggest that age-related changes in focus switching might mediate
      developmental changes in WMU performance.

PMID- 25756939
TI  - I don't get you. Action observation effects inverted by kinematic variation.
AB  - Recent studies have reported an intricate interplay between affordance and mirror
      effects (the imitation of another agent) when participants attend to the
      concurrent presentation of an object and another agent interacting with it. In
      the present paper, we compare two experimental settings in which an observed
      action was presented as a prime for a task involving the categorization of a
      graspable object. In experiment 1a, the action depicted a reach and grasp gesture
      whereas in experiment 1b, only the reach phase was presented. This modification
      led to very different outcomes. Experiment 1a reflected the traditional imitation
      effect elicited by human motion. Conversely, experiment 1b showed the
      facilitation of contralateral responses. Affordance effects were found in
      experiment 1a only for the RVF. Our results support the view that motor
      simulation processes underlying imitation or joint actions are extremely
      sensitive to specific phase kinematics. 

PMID- 25756940
TI  - March 2015 at a glance.

PMID- 25756941
TI  - Cardiac resynchronization therapy in mild heart failure should be reserved for
      true dyssynchronopathy.

PMID- 25756942
TI  - Neprilysin inhibition to treat heart failure: a tale of science, serendipity, and
      second chances.
AB  - This review describes the role of neprilysin (also known as neutral endopeptidase
      or enkephalinase) in the degradation of natriuretic and other vasoactive
      peptides, including bradykinin and adrenomedullin. The initial development of
      neprilysin inhibitors, then angiotensin converting enzyme-neprilysin inhibitors
      and, most recently, the angiotensin receptor neprilysin inhibitor (ARNI) LCZ696
      (sacubitril valsartan) as an extension of the nurohumoral basis for the treatment
      of heart failure is also summarised. Finally, the implications of the compelling
      benefits of LCZ696 compared with enalapril in the Prospective comparison of ARNI
      with ACEI to Determine Impact on Global Mortality and morbidity in Heart Failure
      trial (PARADIGM-HF) is discussed. 

PMID- 25756943
TI  - Rethinking primary care visits: how much can be eliminated, delegated or
      performed outside of the face-to-face visit?
AB  - RATIONALE, AIMS AND OBJECTIVES: Office visits represent the core component of
      primary care practice, but little is known about what percentage of primary care
      provider (PCP) visit time could be suitable for reassignment to another medical
      home team member or to a non-face-to-face modality (e.g. secure messaging) in
      order to optimize face-to-face PCP visit time. METHOD: We videotaped 121 PCP
      office visits at four Veterans Health Administration Medical Centers and divided
      visits into discrete activity segments. Two physicians reviewed each visit
      recording and provided independent clinical judgments regarding which segments
      might be suitable for reassignment. We examined the activity category
      distribution of visit time rated as needing face-to-face time with a PCP.
      RESULTS: Reviewers judged 53% of the 5398 minutes of rated visit time as suitable
      for reassignment to another team member or modality. The percentage of time rated
      as needing face-to-face PCP care varied greatly by activity category, from a high
      of 73.9% (for examining patients) to a low of 16.2% (for medication review).
      Rater agreement regarding tasks' suitability for reassignment varied across
      activity categories. CONCLUSIONS: These data offer an example of how face-to-face
      PCP visit time might be optimized as practices seek to shift components of
      patient care to other team members and other modalities. Given variations in
      provider preferences and judgments, successful redesign efforts will need to
      involve stakeholders in decisions about how to best utilize medical home
      resources.

PMID- 25756945
TI  - Development of a comprehensive method for analyzing clerodane-type diterpenes and
      phenolic compounds from Casearia sylvestris Swartz (Salicaceae) based on ultra
      high performance liquid chromatography combined with chemometric tools.
AB  - This work describes the development and optimization of an analytical method
      utilizing liquid chromatography and chemometrics to evaluate and differentiate
      two varieties of Casearia sylvestris Swartz (Salicaceae) from Sao Paulo State
      (Brazil) based on their secondary metabolite profiles. Previously, analytical
      studies only concerned the analysis of clerodane-type diterpenes. Therefore,
      considering the importance of including phenolic compounds in such analysis, we
      used design of experiments to simultaneously extract and detect the largest
      number of compounds from both chemical classes. This new strategy allowed a
      comprehensive chromatographic analysis of C. sylvestris, and the results for the
      two varieties exhibited an interesting distribution according to their original
      ecosystems, suggesting a strong correlation to the main metabolites found in each
      species group. Besides their inherent morphological differences, C. sylvestris
      variety lingua, mainly found in Cerrado areas, predominantly contains phenolic
      compounds, while C. sylvestris variety sylvestris, mainly found in Atlantic
      Forest areas, contains mostly clerodane-type diterpenes. Finally, it was also
      possible to observe differences in the secondary metabolite composition within
      each group depending on the place where samples were collected. 

PMID- 25756946
TI  - Guest-induced 2-D metallopolycapsular networks based on a 1,3-alternate
      calix[4]arene derivative.
AB  - Solvothermal reactions of the calix[4]arene tetraacetic acid (H4 CTA) with zinc
      nitrate in the presence of alpha,omega-diaminoalkanes afford two-dimensional
      metallopolycapsular networks of the formula {[Me2 NH2 ]2 [G@(Zn2 (CTA)2 )]?(DMF)2
      ?(H2 O)4 }n (G=(+) NH3 -(CH2 )n -NH3 (+) , n=2, 3, 4; DMF=N,N-dimethylformamide).
      These metallopolycapsular networks are built up of metallocapsules that consist
      of two CTA and two Zn(II) ions. Short alkanediyldiammonium ((+) NH3 -(CH2 )n -NH3
      (+) , n=2, 3, 4) guest ions are accommodated in each capsule of the
      metallopolycapsular network through a variety of supramolecular interactions. The
      thermal behaviours and the solid-state photoluminescent properties of these
      complexes were also investigated. 

PMID- 25756944
TI  - Metalloprotease NleC suppresses host NF-kappaB/inflammatory responses by cleaving
      p65 and interfering with the p65/RPS3 interaction.
AB  - Attaching/Effacing (A/E) pathogens including enteropathogenic Escherichia coli
      (EPEC), enterohemorrhagic E. coli (EHEC) and the rodent equivalent Citrobacter
      rodentium are important causative agents of foodborne diseases. Upon infection, a
      myriad of virulence proteins (effectors) encoded by A/E pathogens are injected
      through their conserved type III secretion systems (T3SS) into host cells where
      they interfere with cell signaling cascades, in particular the nuclear factor
      kappaB (NF-kappaB) signaling pathway that orchestrates both innate and adaptive
      immune responses for host defense. Among the T3SS-secreted non-LEE-encoded (Nle)
      effectors, NleC, a metalloprotease, has been recently elucidated to modulate host
      NF-kappaB signaling by cleaving NF-kappaB Rel subunits. However, it remains
      elusive how NleC recognizes NF-kappaB Rel subunits and how the NleC-mediated
      cleavage impacts on host immune responses in infected cells and animals. In this
      study, we show that NleC specifically targets p65/RelA through an interaction
      with a unique N-terminal sequence in p65. NleC cleaves p65 in intestinal
      epithelial cells, albeit a small percentage of the molecule, to generate the p651
      38 fragment during C. rodentium infection in cultured cells. Moreover, the NleC
      mediated p65 cleavage substantially affects the expression of a subset of NF
      kappaB target genes encoding proinflammatory cytokines/chemokines, immune cell
      infiltration in the colon, and tissue injury in C. rodentium-infected mice.
      Mechanistically, the NleC cleavage-generated p651-38 fragment interferes with the
      interaction between p65 and ribosomal protein S3 (RPS3), a 'specifier' subunit of
      NF-kappaB that confers a subset of proinflammatory gene transcription, which
      amplifies the effect of cleaving only a small percentage of p65 to modulate NF
      kappaB-mediated gene expression. Thus, our results reveal a novel mechanism for
      A/E pathogens to specifically block NF-kappaB signaling and inflammatory
      responses by cleaving a small percentage of p65 and targeting the p65/RPS3
      interaction in host cells, thus providing novel insights into the pathogenic
      mechanisms of foodborne diseases.

PMID- 25756947
TI  - Hirsutenone Directly Targets PI3K and ERK to Inhibit Adipogenesis in 3T3-L1
      Preadipocytes.
AB  - Adipogenesis is a key driver of the expansion of adipose tissue mass that causes
      obesity. Hirsutenone (HST) is an active botanical diarylheptanoid present in
      Alnus species. In this study, we evaluated the effects of HST on adipogenesis,
      its mechanisms of action and the molecular targets involved. Using Oil Red O
      staining, we observed that HST dose-dependently suppresses lipid accumulation
      during adipogenesis in 3T3-L1 preadipocytes, concomitant with a decrease in
      peroxisome proliferator-activated receptor-gamma (PPARgamma), CCAAT/enhancer
      binding protein alpha (C/EBPalpha) and fatty acid synthase (FAS) protein
      expression. This inhibitory effect was largely limited to the early stage of
      adipogenesis, which includes mitotic clonal expansion (MCE), as evidenced by
      delayed cell cycle entry of preadipocytes from G1 to S phase. Furthermore, the
      regulation of MCE was accompanied by suppression of phosphatidylinositol 3-kinase
      (PI3K) and extracellular-regulated kinase (ERK) activity. HST was also shown to
      bind directly to PI3K and ERK1 in a non-ATP competitive manner. Our results
      suggest that HST attenuates adipogenesis by directly targeting PI3K and ERK
      during MCE in 3T3-L1 preadipocytes, underscoring the potential therapeutic
      application of HST in preventing obesity.

PMID- 25756948
TI  - Catalytic enantioselective allenoate-alkene [2 + 2] cycloadditions.
AB  - Catalytic enantioselective [2 + 2] cycloadditions between allenoates and alkenes
      is disclosed. The method functions well for a variety of alkenes, and the
      products are generated with excellent levels of enantioselectivity. One of the
      most significant aspects of the present method is that unactivated alkenes are
      suitable substrates for this method, which is distinctly different from nearly
      all other catalytic enantioselective [2 + 2] cycloaddition methods. 

PMID- 25756949
TI  - Direct observation of nanoscale Pt electrode agglomeration at the triple phase
      boundary.
AB  - Nanoporous platinum electrode thin films were delaminated from yttria-stabilized
      zirconia (YSZ) substrates via double cantilever beam delamination to reveal the
      structure located at the interface between electrode and electrolyte. The
      thermally driven morphological evolution between the electrode top surface and
      the substrate contact interface of agglomerated nanoporous platinum thin films
      were compared. We found the temperature required for significant agglomeration to
      occur was approximately 100  degrees C higher at the electrolyte contact
      interface side than at the top surface side. Judging the reaction active site
      from the electrode top surface could be inaccurate because higher resistance of
      thermal agglomeration at the interface could retain the reaction active site
      during fuel cell operation. 

PMID- 25756950
TI  - High Prevalence of CTX-M Beta-Lactamases in Enterobacteriaceae from Healthy
      Individuals in Guangzhou, China.
AB  - This study aimed to determine the prevalence of extended-spectrum beta-lactamases
      (ESBLs) in Enterobacteriaceae and to characterize the genetic composition of ESBL
      determinants among Enterobacteriaceae isolates from healthy people in Guangzhou,
      China. A total of 200 rectal swab samples were collected from healthy
      asymptomatic individuals and tested for ESBL production using ChromID ESBL agar.
      Phenotypic ESBL producers were screened for blaCTX-M, blaTEM, and blaSHV genes
      using PCR and DNA sequencing. The prevalence of ESBL-producing Enterobacteriaceae
      among rectal swab samples was 69.5%. All ESBL-producing isolates harbored blaCTX
      M genes (n=138) except for one isolate that harbored blaSHV-2a. Eleven CTX-M ESBL
      genes were detected. The most predominant CTX-M-type genes were blaCTX-M-14
      (n=82), followed by blaCTX-M-55 (n=19), blaCTX-M-65 (n=10), and blaCTX-M-27
      (n=9). Isolates carrying blaCTX-M-38,-3,-15,-14b,-98,-121 and -123 were also
      identified. Molecular homology analysis of the selected isolates was performed by
      phylogenetic grouping and multilocus sequence typing and indicated that the
      predominant clone belonged to A-CC10. This study showed a high rate of CTX-M-type
      ESBL genes among Enterobacteriaceae isolates from healthy individuals in China. 

PMID- 25756951
TI  - Dipole-moment-driven cooperative supramolecular polymerization.
AB  - While the mechanism of self-assembly of pi-conjugated molecules has been well
      studied to gain control over the structure and functionality of supramolecular
      polymers, the intermolecular interactions underpinning it are poorly understood.
      Here, we study the mechanism of self-assembly of perylene bisimide derivatives
      possessing dipolar carbonate groups as linkers. It was observed that the
      combination of carbonate linkers and cholesterol/dihydrocholesterol self
      assembling moieties led to a cooperative mechanism of self-assembly. Atomistic
      molecular dynamics simulations of an assembly in explicit solvent strongly
      suggest that the dipole-dipole interaction between the carbonate groups imparts a
      macro-dipolar character to the assembly. This is confirmed experimentally through
      the observation of a significant polarization in the bulk phase for molecules
      following a cooperative mechanism. The cooperativity is attributed to the
      presence of dipole-dipole interaction in the assembly. Thus, anisotropic long
      range intermolecular interactions such as dipole-dipole interaction can serve as
      a way to obtain cooperative self-assembly and aid in rationalizing and predicting
      the mechanisms in various synthetic supramolecular polymers. 

PMID- 25756952
TI  - microRNA-18b modulates insulin-like growth factor-1 expression in deer antler
      cell proliferation by directly targeting its 3' untranslated region.
AB  - Insulin-like growth factor-1 (IGF-1) is a multipromoter gene that has complex
      biological functions and plays an important role in Chinese sika deer antler cell
      differentiation and proliferation. microRNAs and their roles in deer antler
      growth have attracted much attention. In the present study, to investigate the
      effect of microRNAs on the regulation of IGF-1 during the rapid growth of
      antlers, miRNA GeneChip analysis and TargetScan Human software were used to
      screen microRNAs that bind to the 3' untranslated region (3'UTR) of IGF-1. The
      results indicated that a significantly differential expression of miR-18b was
      observed in cartilage and mesenchymal of antler tip tissue and the presence of
      miR-18b-binding sites within the IGF-1 3'UTR. A miR-18b mimic was then
      transfected into antler cartilage cells to overexpress miR-18b and the expression
      levels were quantified by real-time PCR. Real-time PCR showed that the expression
      level of miR-18b in transfected cells was significantly increased compared with
      the control group (p<0.01). Dual luciferase assays revealed that miR-18b
      decreased the fluorescence value of the luciferase reporter gene in the group
      transfected with the wild-type vector of IGF-1 3'UTR. In contrast, the relative
      luciferase activity in the group transfected with the mutant vector of IGF-1
      3'UTR did not change obviously. MTT assays and cell cycle analyses confirmed that
      overexpression of the miR-18b mimic inhibited the proliferation of cartilage
      cells. In contrast, transfection of a miR-18b inhibitor increased the cell
      proliferation rate. Furthermore, Western blot analyses revealed that
      overexpression of miR-18b mimics downregulated the protein levels of IGF-1, while
      IGF-1 expression increased after transfection of miR-18b inhibitors. Taken
      together, our findings show that miR-18b is a potentially novel target in deer
      antler cell proliferation. miR-18b may modulate IGF-1 expression of sika deer
      antler. 

PMID- 25756953
TI  - Pokeweed antiviral protein: its cytotoxicity mechanism and applications in plant
      disease resistance.
AB  - Pokeweed antiviral protein (PAP) is a 29 kDa type I ribosome inactivating protein
      (RIP) found in pokeweed plants. Pokeweed produces different forms of PAP. This
      review focuses on the spring form of PAP isolated from Phytolacca americana
      leaves. PAP exerts its cytotoxicity by removing a specific adenine from the alpha
      sarcin/ricin loop of the large ribosomal RNA. Besides depurination of the rRNA,
      PAP has additional activities that contribute to its cytotoxicity. The mechanism
      of PAP cytotoxicity is summarized based on evidence from the analysis of
      transgenic plants and the yeast model system. PAP was initially found to be anti
      viral when it was co-inoculated with plant viruses onto plants. Transgenic plants
      expressing PAP and non-toxic PAP mutants have displayed broad-spectrum resistance
      to both viral and fungal infection. The mechanism of PAP-induced disease
      resistance in transgenic plants is summarized. 

PMID- 25756955
TI  - Role of Pneumococcal Autolysin for KLF4 Expression and Chemokine Secretion in
      Lung Epithelium.
AB  - In severe pneumococcal pneumonia, the delicate balance between a robust
      inflammatory response necessary to kill bacteria and the loss of organ function
      determines the outcome of disease. In this study, we tested the hypothesis that
      Krueppel-like factor (KLF) 4 may counter-regulate Streptococcus pneumoniae
      related human lung epithelial cell activation using the potent proinflammatory
      chemokine IL-8 as a model molecule. Pneumococci induced KLF4 expression in human
      lung, in primary human bronchial epithelial cells, and in the lung epithelial
      cell line BEAS-2B. Whereas proinflammatory cell activation depends mainly on the
      classical Toll-like receptor 2-mitogen-activated protein kinase or
      phosphatidylinositide 3-kinase and NF-kappaB pathways, the induction of KLF4
      occurred independently of these molecules but relied, in general, on tyrosine
      kinase activation and, in part, on the src kinase family member yamaguchi sarcoma
      viral oncogene homolog (yes) 1. The up-regulation of KLF4 depended on the
      activity of the main pneumococcal autolysin LytA. KLF4 overexpression suppressed
      S. pneumoniae-induced NF-kappaB and IL-8 reporter gene activation and release,
      whereas small interfering RNA-mediated silencing of KLF4 or yes1 kinase led to an
      increase in IL-8 release. The KLF4-dependent down-regulation of NF-kappaB
      luciferase activity could be rescued by the overexpression of the histone
      acetylase p300/cAMP response element-binding protein-associated factor. In
      conclusion, KLF4 acts as a counter-regulatory transcription factor in pneumococci
      related proinflammatory activation of lung epithelial cells, thereby potentially
      preventing lung hyperinflammation and subsequent organ failure.

PMID- 25756956
TI  - Unusual and tunable one-photon nonlinearity in gold-dye plexcitonic Fano systems.
AB  - Recent studies of the coupling between the plasmonic excitations of metallic
      nanostructures with the excitonic excitations of molecular species have revealed
      a rich variety of emergent phenomena known as plexcitonics. Here, we use a
      combined experimental and theoretical approach to demonstrate new and intriguing
      aspects in the ultrafast nonlinear responses of strongly coupled hybrid Fano
      systems consisting of gold nanorods decorated with near-infrared dye molecules.
      We show that the severely suppressed linear absorption around the Fano dip
      significantly enhances the unidirectional energy transfer from the plasmons to
      the excitons and further allows one-photon nonlinearity to be drastically and
      reversibly tuned. These striking observations are interpreted within a
      microscopic model stressing on two competing processes: saturated plasmonic
      absorption and weakened destructive Fano interference from the bleached excitonic
      absorption. The unusually strong one-photon nonlinearity revealed here provides a
      promising strategy in fabricating nanoplasmonic devices with both pronounced
      nonlinearities and good figures of merit. 

PMID- 25756954
TI  - Ergot alkaloids produced by endophytic fungi of the genus Epichloe.
AB  - The development of fungal endophytes of the genus Epichloe in grasses results in
      the production of different groups of alkaloids, whose mechanism and biological
      spectrum of toxicity can differ considerably. Ergot alkaloids, when present in
      endophyte-infected tall fescue, are responsible for "fescue toxicosis" in
      livestock, whereas indole-diterpene alkaloids, when present in endophyte-infected
      ryegrass, are responsible for "ryegrass staggers". In contrast, peramine and
      loline alkaloids are deterrent and/or toxic to insects. Other toxic effects in
      livestock associated with the consumption of endophyte-infected grass that
      contain ergot alkaloids include the "sleepy grass" and "drunken horse grass"
      diseases. Although ergovaline is the main ergopeptine alkaloid produced in
      endophyte-infected tall fescue and is recognized as responsible for fescue
      toxicosis, a number of questions still exist concerning the profile of alkaloid
      production in tall fescue and the worldwide distribution of tall fescue
      toxicosis. The purpose of this review is to present ergot alkaloids produced in
      endophyte-infected grass, the factors of variation of their level in plants, and
      the diseases observed in the mammalian species as relate to the profiles of
      alkaloid production. In the final section, interactions between ergot alkaloids
      and drug-metabolizing enzymes are presented as mechanisms that could contribute
      to toxicity. 

PMID- 25756958
TI  - Proteomic analysis of human Sonic Hedgehog (SHH) medulloblastoma stem-like cells.
AB  - Human medulloblastoma (MB) is a malignant brain tumor that comprises four
      distinct molecular subgroups including the Sonic Hedgehog (SHH)-MB group. A
      leading cause of the SHH subgroup is an aberrant activation of the SHH pathway, a
      developmental signaling that regulates postnatal development of the cerebellum by
      promoting the mitotic expansion of granule neural precursors (GNPs) in the
      external granule layer (EGL). The abnormal SHH signaling pathway drives not only
      SHH-MB but also its cancer stem-like cells (SLCs), which represent a fraction of
      the tumor cell population that maintain cancer growth and have been associated
      with high grade tumors. Here, we report the first proteomic analysis of human SHH
      MB SLCs before and after Retinoic Acid (RA)-induced differentiation. A total of
      994 nLC-MS buckets were statistically analysed returning 68 modulated proteins
      between SLCs and their differentiated counterparts. Heat Shock Protein 70 (Hsp70)
      was one of the proteins that characterized the protein profile of SLCs. By means
      of Ingenuity Pathway Analysis (IPA), Genomatix analysis and extending the network
      obtained using the differentially expressed proteins we found a correlation
      between Hsp70 and the NF-kappaB complex. A key driver of the SHH-MB group is cMET
      whose downstream proliferation/survival signalling is indeed via PI3K/Akt/NF
      kappaB. We confirmed the results of the proteomic analysis by western blot,
      underlining that a P-p65/NF-kappaB activatory complex is highly expressed in
      SLCs. Taking together these results we define a new protein feature of SHH-MB
      SLCs. 

PMID- 25756957
TI  - Substrate stiffness regulates B-cell activation, proliferation, class switch, and
      T-cell-independent antibody responses in vivo.
AB  - B cells use B-cell receptors (BCRs) to sense antigens that are usually presented
      on substrates with different stiffness. However, it is not known how substrate
      stiffness affects B-cell proliferation, class switch, and in vivo antibody
      responses. We addressed these questions using polydimethylsiloxane (PDMS)
      substrates with different stiffness (20 or 1100 kPa). Live cell imaging
      experiments suggested that antigens on stiffer substrates more efficiently
      trigger the synaptic accumulation of BCR and phospho-Syk molecules compared with
      antigens on softer substrates. In vitro expansion of mouse primary B cells shows
      different preferences for substrate stiffness when stimulated by different
      expansion stimuli. LPS equally drives B-cell proliferation on stiffer or softer
      substrates. Anti-CD40 antibodies enhance B-cell proliferation on stiffer
      substrates, while antigens enhance B-cell proliferation on softer substrates
      through a mechanism involving the enhanced phosphorylation of PI3K, Akt, and
      FoxO1. In vitro class switch differentiation of B cells prefers softer
      substrates. Lastly, NP67-Ficoll on softer substrates accounted for an enhanced
      antibody response in vivo. Thus, substrate stiffness regulates B-cell activation,
      proliferation, class switch, and T cell independent antibody responses in vivo,
      suggesting its broad application in manipulating the fate of B cells in vitro and
      in vivo. 

PMID- 25756959
TI  - The Influence of Physical Fitness and Playing Standard on Pacing Strategies
      During a Team-Sport Tournament.
AB  - PURPOSE: To assess the influence of playing standard and physical fitness on
      pacing strategies during a junior team-sport tournament. METHODS: A between
      groups, repeated-measures design was used. Twenty-eight junior team-sport players
      (age 16.6 +/- 0.5 y, body mass 79.9 +/- 12.0 kg) from a high-standard and low
      standard team participated in a junior rugby league tournament, competing in 5
      games over 4 d (4 * 40-min and 1 * 50-min game). Players wore global positioning
      system (GPS) microtechnology during each game to provide information on match
      activity profiles. The Yo-Yo Intermittent Recovery Test (level 1) was used to
      assess physical fitness before the competition. RESULTS: High-standard players
      had an initially higher pacing strategy than the low-standard players, covering
      greater distances at high (ES = 1.32) and moderate speed (ES = 1.41) in game 1
      and moderate speed (ES = 1.55) in game 2. However, low-standard players increased
      their playing intensity across the competition (ES = 0.57-2.04). High
      standard/high-fitness players maintained a similar playing intensity, whereas
      high-standard/low-fitness players reduced their playing intensities across the
      competition. CONCLUSIONS: Well-developed physical fitness allows for a higher
      intensity pacing strategy that can be maintained throughout a tournament. High
      standard/low-fitness players reduce playing intensity, most likely due to
      increased levels of fatigue as the competition progresses. Low-standard players
      adopt a pacing strategy that allows them to conserve energy to produce an "end
      spurt" in the latter games. Maximizing endurance fitness across an entire playing
      group will maximize playing intensity and minimize performance reductions during
      the latter stages of a tournament.

PMID- 25756960
TI  - Quantitative proteomics reveal distinct protein regulations caused by
      Aggregatibacter actinomycetemcomitans within subgingival biofilms.
AB  - Periodontitis is an infectious disease that causes the inflammatory destruction
      of the tooth-supporting (periodontal) tissues, caused by polymicrobial biofilm
      communities growing on the tooth surface. Aggressive periodontitis is strongly
      associated with the presence of Aggregatibacter actinomycetemcomitans in the
      subgingival biofilms. Nevertheless, whether and how A. actinomycetemcomitans
      orchestrates molecular changes within the biofilm is unclear. The aim of this
      work was to decipher the interactions between A. actinomycetemcomitans and other
      bacterial species in a multi-species biofilm using proteomic analysis. An in
      vitro 10-species "subgingival" biofilm model, or its derivative that included
      additionally A. actinomycetemcomitans, were anaerobically cultivated on
      hydroxyapatite discs for 64 h. When present, A. actinomycetemcomitans formed
      dense intra-species clumps within the biofilm mass, and did not affect the
      numbers of the other species in the biofilm. Liquid chromatography-tandem mass
      spectrometry was used to identify the proteomic content of the biofilm lysate. A
      total of 3225 and 3352 proteins were identified in the biofilm, in presence or
      absence of A. actinomycetemcomitans, respectively. Label-free quantitative
      proteomics revealed that 483 out of the 728 quantified bacterial proteins
      (excluding those of A. actinomycetemcomitans) were accordingly regulated.
      Interestingly, all quantified proteins from Prevotella intermedia were up
      regulated, and most quantified proteins from Campylobacter rectus, Streptococcus
      anginosus, and Porphyromonas gingivalis were down-regulated in presence of A.
      actinomycetemcomitans. Enrichment of Gene Ontology pathway analysis showed that
      the regulated groups of proteins were responsible primarily for changes in the
      metabolic rate, the ferric iron-binding, and the 5S RNA binding capacities, on
      the universal biofilm level. While the presence of A. actinomycetemcomitans did
      not affect the numeric composition or absolute protein numbers of the other
      biofilm species, it caused qualitative changes in their overall protein
      expression profile. These molecular shifts within the biofilm warrant further
      investigation on their potential impact on its virulence properties, and
      association with periodontal pathogenesis. 

PMID- 25756961
TI  - Concurrent Targeting of KRAS and AKT by MiR-4689 Is a Novel Treatment Against
      Mutant KRAS Colorectal Cancer.
AB  - KRAS mutations are a major cause of drug resistance to molecular-targeted
      therapies. Aberrant epidermal growth factor receptor (EGFR) signaling may cause
      dysregulation of microRNA (miRNA) and gene regulatory networks, which leads to
      cancer initiation and progression. To address the functional relevance of miRNAs
      in mutant KRAS cancers, we transfected exogenous KRAS(G12V) into human embryonic
      kidney 293 and MRC5 cells with wild-type KRAS and BRAF genes, and we
      comprehensively profiled the dysregulated miRNAs. The result showed that mature
      miRNA oligonucleotide (miR)-4689, one of the significantly down-regulated miRNAs
      in KRAS(G12V) overexpressed cells, was found to exhibit a potent growth
      inhibitory and proapoptotic effect both in vitro and in vivo. miR-4689 expression
      was significantly down-regulated in cancer tissues compared to normal mucosa, and
      it was particularly decreased in mutant KRAS CRC tissues. miR-4689 directly
      targets v-ki-ras2 kirsten rat sarcoma viral oncogene homolog (KRAS) and v-akt
      murine thymoma viral oncogene homolog 1(AKT1), key components of two major
      branches in EGFR pathway, suggesting KRAS overdrives this signaling pathway
      through inhibition of miR-4689. Overall, this study provided additional evidence
      that mutant KRAS functions as a broad regulator of the EGFR signaling cascade by
      inhibiting miR-4689, which negatively regulates both RAS/mitogen-activated
      protein kinase (MAPK) and phosphoinositide 3-kinase (PI3K)/AKT pathways. These
      activities indicated that miR-4689 may be a promising therapeutic agent in mutant
      KRAS CRC. 

PMID- 25756962
TI  - Improved cell-penetrating zinc-finger nuclease proteins for precision genome
      engineering.
AB  - Safe, efficient, and broadly applicable methods for delivering site-specific
      nucleases into cells are needed in order for targeted genome editing to reach its
      full potential for basic research and medicine. We previously reported that zinc
      finger nuclease (ZFN) proteins have the innate capacity to cross cell membranes
      and induce genome modification via their direct application to human cells. Here,
      we show that incorporation of tandem nuclear localization signal (NLS) repeats
      into the ZFN protein backbone enhances cell permeability nearly 13-fold and that
      single administration of multi-NLS ZFN proteins leads to genome modification
      rates of up to 26% in CD4(+) T cells and 17% in CD34(+) hematopoietic
      stem/progenitor cells. In addition, we show that multi-NLS ZFN proteins attenuate
      off-target effects and that codelivery of ZFN protein pairs facilitates dual gene
      modification frequencies of 20-30% in CD4(+) T cells. These results illustrate
      the applicability of ZFN protein delivery for precision genome engineering. 

PMID- 25756963
TI  - Effectiveness of traditional Chinese medicine as an adjunct therapy for
      Parkinson's disease: a systematic review and meta-analysis.
AB  - BACKGROUND: Idiopathic Parkinson disease (PD) is a common neurodegenerative
      disease that seriously hinders limb activities and affects patients' lives. We
      performed a meta-analysis aiming to systematically review and quantitatively
      synthesize the efficacy and safety of traditional Chinese medicine (TCM) as an
      adjunct therapy for clinical PD patients. METHODS: An electronic search was
      conducted in PubMed, Cochrane Controlled Trials Register, China National
      Knowledge Infrastructure, Chinese Scientific Journals Database and Wanfang data
      to identify randomized trials evaluating TCM adjuvant therapy versus conventional
      treatment. The change from baseline of the Unified Parkinson's Disease Rating
      Scale score (UPDRS) was used to estimate the effectiveness of the therapies.
      RESULTS: Twenty-seven articles involving 2314 patients from 1999 to 2013 were
      included. Potentially marked improvements were shown in UPDRS I (SMD 0.68, 95%CI
      0.38, 0.98), II (WMD 2.41, 95%CI 1.66, 2.62), III (WMD 2.45, 95%CI 2.03, 2.86),
      IV (WMD 0.32, 95%CI 0.15, 049) and I-IV total scores (WMD 6.18, 95%CI 5.06, 7.31)
      in patients with TCM plus dopamine replacement therapy (DRT) compared to DRT
      alone. Acupuncture add-on therapy was markedly beneficial for improving the UPDRS
      I-IV total score of PD patients (WMD 10.96, 95%CI 5.85, 16.07). However, TCM
      monotherapy did not improve the score. The effectiveness seemed to be more
      obvious in PD patients with longer adjunct durations. TCM adjuvant therapy was
      generally safe and well tolerated. CONCLUSIONS: Although the data were limited by
      methodological flaws in many studies, the evidence indicates the potential
      superiority of TCM as an alternative therapeutic for PD treatment and justifies
      further high-quality studies.

PMID- 25756966
TI  - A new standard of care? Studies on febuxostat in the management of hyperuricemia
      with and without gout: Erratum.
AB  - [This corrects the article on p. S11 in vol. 17, issue 4 suppl 2, PMID: 21654264.
      Kamatani Naoyuki should be Naoyuki Kamatani and Hosoya Tatsuo should be Tatsuo
      Hosoya.]. 

PMID- 25756967
TI  - Shared decision making: roots in antiquity.

PMID- 25756964
TI  - Blood Pressure and Same-Day Exposure to Air Pollution at School: Associations
      with Nano-Sized to Coarse PM in Children.
AB  - BACKGROUND: Ultrafine particles (UFP) may contribute to the cardiovascular
      effects of particulate air pollution, partly because of their relatively
      efficient alveolar deposition. OBJECTIVE: In this study, we assessed associations
      between blood pressure and short-term exposure to air pollution in a population
      of schoolchildren. METHODS: In 130 children (6-12 years of age), blood pressure
      was determined during two periods (spring and fall 2011). We used mixed models to
      study the association between blood pressure and ambient concentrations of
      particulate matter and ultrafine particles measured in the schools' playground.
      RESULTS: Independent of sex, age, height, and weight of the child, parental
      education, neighborhood socioeconomic status, fish consumption, heart rate,
      school, day of the week, season, wind speed, relative humidity, and temperature
      on the morning of examination, an interquartile range (860 particles/cm3)
      increase in nano-sized UFP fraction (20-30 nm) was associated with a 6.35 mmHg
      (95% CI: 1.56, 11.14; p = 0.01) increase in systolic blood pressure. For the
      total UFP fraction, systolic blood pressure was 0.79 mmHg (95% CI: 0.07, 1.51; p
      = 0.03) higher, but no effects on systolic blood pressure were found for the nano
      sized fractions with a diameter > 100 nm, nor PM2.5, PMcoarse, and PM10.
      Diastolic blood pressure was not associated with any of the studied particulate
      mass fractions. CONCLUSION: Children attending school on days with higher UFP
      concentrations (diameter < 100 nm) had higher systolic blood pressure. The
      association was dependent on UFP size, and there was no association with the
      PM2.5 mass concentration.

PMID- 25756965
TI  - Changes in protein expression in two cholangiocarcinoma cell lines undergoing
      formation of multicellular tumor spheroids in vitro.
AB  - Epithelial-to-Mesenchymal Transition (EMT) is relevant in malignant growth and
      frequently correlates with worsening disease progression due to its implications
      in metastases and resistance to therapeutic interventions. Although EMT is known
      to occur in several types of solid tumors, the information concerning tumors
      arising from the epithelia of the bile tract is still limited. In order to
      approach the problem of EMT in cholangiocarcinoma, we decided to investigate the
      changes in protein expression occurring in two cell lines under conditions
      leading to growth as adherent monolayers or to formation of multicellular tumor
      spheroids (MCTS), which are considered culture models that better mimic the
      growth characteristics of in-vivo solid tumors. In our system, changes in
      phenotypes occur with only a decrease in transmembrane E-cadherin and vimentin
      expression, minor changes in the transglutaminase protein/activity but with
      significant differences in the proteome profiles, with declining and increasing
      expression in 6 and in 16 proteins identified by mass spectrometry. The arising
      protein patterns were analyzed based on canonical pathways and network analysis.
      These results suggest that significant metabolic rearrangements occur during the
      conversion of cholangiocarcinomas cells to the MCTS phenotype, which most likely
      affect the carbohydrate metabolism, protein folding, cytoskeletal activity, and
      tissue sensitivity to oxygen. 

PMID- 25756970
TI  - Adapting shared decision making for individuals with severe mental illness.
AB  - Shared decision making has found its way into mental health care to a limited
      extent only, and especially "challenging" patients do not benefit from this
      approach. The authors describe barriers to shared decision making among mental
      health professionals and among patients. They propose an integrative approach-SDM
      PLUS-that fosters shared decision making in mental health settings. SDM-PLUS
      empowers both patients and mental health care providers. Patients are empowered
      to become more active and self-confident and to acquire greater skills in regard
      to health literacy and communication. Providers are trained in analyzing
      decisional situations and are empowered to use a wider array of communication
      strategies to optimize patient participation. 

PMID- 25756971
TI  - Commentary: shared decision making must be adopted, not adapted.

PMID- 25756973
TI  - Social inequalities and antidepressant use in Canada and France: in reply.

PMID- 25756972
TI  - Social inequalities and antidepressant use in Canada and France.

PMID- 25756974
TI  - Time to invest in engagement.

PMID- 25756975
TI  - Addressing the shortage of psychiatrists in rural areas.

PMID- 25756990
TI  - Predictors of irrational parenthood cognitions in an Iranian group of infertile
      women.
AB  - OBJECTIVES: The aim of this study was to investigate possible predictors of
      irrational parenthood cognitions among infertile women seeking treatment.
      METHODS: In a cross-sectional study, 300 women who visited an Infertility Center
      in Iran during 2010 were studied. A pre-validated inventory was used to assess
      irrational parenthood cognitions. Potential predictors of the total irrational
      parenthood cognitions score were assessed. RESULTS: Mean irrational parenthood
      cognition score was 39.7(Range 0-56). Through bivariate analysis, the score on
      irrational parenthood cognition was inversely correlated with age and positively
      correlated with length of time seeking for infertility treatment and length of
      time expecting pregnancy. In a multivariate model, infertile women with higher
      education, especially academic education, or those with higher economic status
      were less likely to have irrational parenthood cognitions. However, higher
      motherhood motivation, no previous experience of pregnancy and being under social
      pressure, from others around, increased the likelihood of having irrational
      parenthood cognitions. CONCLUSIONS: Some variables such as female spouse's
      educational level and being under social pressure can independently predict
      irrational parenthood cognitions among infertile women that may be of use in
      designing health promotion plans in order to target the vulnerable women.

PMID- 25756992
TI  - Characterization of methicillin-resistant and -susceptible staphylococcal
      isolates from bovine milk in northwestern china.
AB  - Emergence of methicillin-resistant Staphylococcus aureus (MRSA) and methicillin
      resistant coagulase-negative staphylococci (MR-CoNS) in bovine milk is a major
      public health concern. The primary purpose of this research was to determine
      molecular genetic characteristics and antibiotic resistance of staphylococcal
      isolates recovered from milk of mastitic cows in the Shaanxi Province in
      Northwestern China. One hundred and thirteen methicillin-susceptible
      Staphylococcus aureus (MSSA), one mecA-positive and phenotype-positive MRSA,
      seven mecA- and mecC- negative but phenotype-positive MRSA and two MR-CoNS
      including one oxacillin-susceptible mecA-positive Staphylococcus haemolyticus (OS
      MRSH) and one mecA-positive and methicillin-resistant Staphylococcus epidermidis
      (MRSE) isolates were recovered from 214 quarter milk samples on 4 dairy farms.
      All above 123 isolates were subjected to antibiotic resistance profiling. S.
      aureus isolates were also genotyped using the spa typing and the multilocus
      sequence typing (MLST). Eight MRSA and 2 MR-CoNS isolates were additionally
      tested for SCCmec types. Resistance was common among isolates against ampicillin
      or penicillin (80.5%), kanamycin (68.3%), gentamicin (67.5%), tetracycline
      (43.9%) and chloramphenicol (30.1%). However, no isolate was resistant to
      vancomycin or teicoplanin. Twenty, 29 and 58 isolates showed resistance to 1, 2
      or more than 2 antibiotics, respectively. The predominant multidrug resistance
      profile was penicillin/ampicillin/kanamycin/gentamicin/tetracycline (46
      isolates). Most S. aureus isolates belonged to spa types t524 (n = 63), t11772 (a
      new type, n = 31) and t4207 (n = 15). At the same time, MLST types ST71 (n = 67)
      and ST2738 (a new type, n = 45) were identified as dominant sequence types. The
      mecA-positive and phenotype-positive MRSA isolate had a composite genotype t524
      ST71-SCCmecIVa, while 7 mecA-negative but phenotype-positive MRSA isolates were
      all t524-ST71. The OS-MRSH isolate contained a type V SCCmec cassette, while the
      MRSE isolate possessed a non-typeable SCCmec. The spa-MLST types t11772-ST2738 (n
      = 27), t11807-ST2683 (n = 4) and t11771-ST2738 (n = 3) were newly identified
      genotypes of S. aureus. These new genotypes and multidrug-resistant staphylococci
      could pose additional threat to animal and human health. 

PMID- 25756993
TI  - Electromagnetic absorption of semiconductor 2D Majorana nanowires.
AB  - We calculate the cross section for the electromagnetic absorption of planar 2D
      Majorana nanowires. The electromagnetic field is described in the dipole
      approximation. We discuss the signatures on the cross section of a near-zero
      energy mode. A low energy peak for transverse polarization, absent in the
      longitudinal one, reveals the presence of the Majorana-like state. This peak is
      relatively robust against the thermal smearing of the level occupations. We
      consider the influence of optical masks hiding parts of the nanowire from the
      radiation. 

PMID- 25756991
TI  - The semantic variant of primary progressive aphasia: clinical and neuroimaging
      evidence in single subjects.
AB  - BACKGROUND/AIM: We present a clinical-neuroimaging study in a series of patients
      with a clinical diagnosis of semantic variant of primary progressive aphasia
      (svPPA), with the aim to provide clinical-functional correlations of the
      cognitive and behavioral manifestations at the single-subject level. METHODS: We
      performed neuropsychological investigations, 18F-FDG-PET single-subject and group
      analysis, with an optimized SPM voxel-based approach, and correlation analyses. A
      measurement of white matter integrity by means of diffusion tensor imaging (DTI)
      was also available for a subgroup of patients. RESULTS: Cognitive assessment
      confirmed the presence of typical semantic memory deficits in all patients, with
      a relative sparing of executive, attentional, visuo-constructional, and episodic
      memory domains. 18F-FDG-PET showed a consistent pattern of cerebral
      hypometabolism across all patients, which correlated with performance in semantic
      memory tasks. In addition, a majority of patients also presented with behavioral
      disturbances associated with metabolic dysfunction in limbic structures. In a
      subgroup of cases the DTI analysis showed FA abnormalities in the inferior
      longitudinal and uncinate fasciculi. DISCUSSION: Each svPPA individual had
      functional derangement involving an extended, connected system within the left
      temporal lobe, a crucial part of the verbal semantic network, as well as an
      involvement of limbic structures. The latter was associated with behavioral
      manifestations and extended beyond the area of atrophy shown by CT scan.
      CONCLUSION: Single-subject 18F-FDG-PET analysis can account for both cognitive
      and behavioral alterations in svPPA. This provides useful support to the clinical
      diagnosis.

PMID- 25756995
TI  - ACSM clinician profile. Jon Patricios, MD, FACSM,.

PMID- 25756994
TI  - Genetic structure is associated with phenotypic divergence in floral traits and
      reproductive investment in a high-altitude orchid from the Iron Quadrangle,
      southeastern Brazil.
AB  - Knowledge of the role of Neotropical montane landscapes in shaping genetic
      connectivity and local adaptation is essential for understanding the evolutionary
      processes that have shaped the extraordinary species diversity in these regions.
      In the present study, we examined the landscape genetics, estimated genetic
      diversity, and explored genetic relationships with morphological variability and
      reproductive strategies in seven natural populations of Cattleya liliputana
      (Orchidaceae). Nuclear microsatellite markers were used for genetic analyses.
      Spatial Bayesian clustering and population-based analyses revealed significant
      genetic structuring and high genetic diversity (He = 0.733 +/- 0.03). Strong
      differentiation was found between populations over short spatial scales (FST =
      0.138, p < 0.001), reflecting the landscape discontinuity and isolation.
      Monmonier's maximum difference algorithm, Bayesian analysis on STRUCTURE and
      principal component analysis identified one major genetic discontinuity between
      populations. Divergent genetic groups showed phenotypic divergence in flower
      traits and reproductive strategies. Increased sexual reproductive effort was
      associated with rock outcrop type and may be a response to adverse conditions for
      growth and vegetative reproduction. Here we discuss the effect of restricted gene
      flow, local adaptation and phenotypic plasticity as drivers of population
      differentiation in Neotropical montane rock outcrops. 

PMID- 25756996
TI  - Pelvic pain from running, rhabdomyolysis from spinning, and leukopenia in
      athletes.

PMID- 25756998
TI  - Doubt.

PMID- 25756999
TI  - Altitude illness.

PMID- 25757000
TI  - It is NOT the gastrocnemius, soleus, or Achilles .... What could it Be? A
      plantaris muscle injury.

PMID- 25757001
TI  - A case of vasovagal syncope in a collegiate swimmer during competition.

PMID- 25757002
TI  - Asymptomatic left ventricular noncompaction--implications for athletic
      participation.
AB  - Left ventricular noncompaction (LVNC) is a poorly understood and much debated
      morphological abnormality of the left ventricular myocardium. Much of what is
      known about this cardiomyopathy derives from large referral centers in patients
      presenting with significant symptoms and advanced disease. Disease progression
      and outcomes for adult patients with incidentally found and asymptomatic LVNC
      have not been established yet. As such, there are currently no evidence-based
      recommendations on clinical follow-up or interventions. Since LVNC's effect on
      athletic participation is unknown, there is insufficient evidence to support
      limiting athletic participation in low-risk individuals. 

PMID- 25757003
TI  - Using lifestyle medicine in U.S. health care to treat obesity: too many bariatric
      surgeries?
AB  - More than one-third of Americans are classified as obese. Many clinicians perform
      bariatric surgery (BSx) when it is said that lifestyle intervention failed.
      However, BSx is medically complex, with extremely variable success, certain
      failures, major complications, and sometimes death. Although many studies declare
      BSx as more effective for producing weight loss than nonsurgical lifestyle
      management, these conclusions are flawed when lifestyle management between
      cohorts are not identical. Lifestyle behavior change is essential to success for
      both surgical and nonsurgical weight loss, as over 50% of BSx patients regain
      weight without lifestyle modification. Indeed, programs that include self-reward
      and reinforcement are extremely effective. It is therefore possible that
      successful BSx is simply an intrinsic reward for an intensive change in lifestyle
      behavior. Accounting for the costs and risks associated with BSx, providing state
      and federal resources for lifestyle behavior change programs could provide a key
      opportunity for the war against obesity. 

PMID- 25757004
TI  - Evidence supporting the need for bariatric surgery to address the obesity
      epidemic in the United States.
AB  - Despite aims at prevention, obesity in the United States is now an epidemic.
      Along with the rise in obesity, the United States has experienced a concomitant
      rise in obesity-related comorbidities. Furthermore overweight and obesity present
      a major economic public health challenge. Physicians are likely to recommend
      weight loss to their overweight patients. Diet, exercise, and behavior
      modification are often effective during the course of treatment but are subject
      to recidivism and post-treatment weight gain. Obesity intervention mandates that
      providers consider the need for surgery in many cases. The three most commonly
      performed weight loss surgical procedures in the United States include gastric
      banding, gastric bypass, and sleeve gastrectomy. Patients undergoing surgery lose
      considerable amounts of excess weight and experience marked improvement in many
      other obesity-related comorbidities. Surgery is a proven therapy for patients who
      do not respond to less invasive measures and should be considered mainstream
      therapy in the treatment of the obesity epidemic. 

PMID- 25757005
TI  - Exercise and the heart--the harm of too little and too much.
AB  - Physical activity and exercise training are underutilized by much of Westernized
      society, and physical inactivity may be the greatest threat to health in the 21st
      century. Many studies have shown a linear relationship between one's activity
      level and heart health, leading to the conclusion that "if some exercise is good,
      more must be better." However, there is evolving evidence that high levels of
      exercise may produce similar or less overall cardiovascular (CV) benefits
      compared with those produced by lower doses of exercise. Very high doses of
      exercise may be associated with increased risk of atrial fibrillation, coronary
      artery disease, and malignant ventricular arrhythmias. These acute bouts of
      excessive exercise may lead to cardiac dilatation, cardiac dysfunction, and
      release of troponin and brain natriuretic peptide. The effects of too little and
      too much exercise on the heart are reviewed in this article, along with
      recommendations to optimize the dose of exercise to achieve heart health. 

PMID- 25757006
TI  - Exercise collapse associated with sickle cell trait (ECAST): case report and
      literature review.
AB  - Sickle cell trait (SCT) has been associated with exertional collapse (ECAST) and
      exercise-related sudden death in athletes and military warfighters. The
      mechanisms underlying ECAST remain controversial in the sports medicine
      community. Multiple case presentations and anecdotal reports postulate the role
      of extraordinary exercise intensity, but other risk factors including
      dehydration, heat, previous exertional rhabdomyolysis, genetic cofactors, and
      dietary supplements have been cited as potential contributors. Others have
      hypothesized some of the aforementioned factors combining in a "perfect storm" to
      trigger ECAST with a resultant potentially fatal "metabolic crisis." This case
      report provides a brief review of SCT as it pertains to exercise in warfighters
      and athletes, identifies known and postulated risk factors associated with ECAST,
      and introduces the potential mechanistic role of the "double hit" as a
      contributor to ECAST. 

PMID- 25757007
TI  - Pain control in austere settings.
AB  - Sporting events, particularly "extreme" sports, are becoming increasingly more
      austere and thus further from readily available fixed facility medical care. The
      provider caring for acute injuries in these more remote locations will be faced
      with the need to treat pain in the injured athlete. This review provides a
      stepwise approach to safe and effective pain control in the austere environment. 

PMID- 25757008
TI  - Jet lag modification.
AB  - Athletes often are required to travel for sports participation, both for practice
      and competition. A number of those crossing multiple time zones will develop jet
      lag disorder with possible negative consequences on their performance. This
      review will discuss the etiology of jet lag disorder and the techniques that are
      available to shorten or minimize its effects. This includes both pharmacological
      and nonpharmacological approaches. 

PMID- 25757009
TI  - The lost art of whole blood transfusion in austere environments.
AB  - The optimal resuscitation fluid for uncontrolled bleeding and hemorrhagic shock
      in both pre- and in-hospital settings has been an ongoing controversy for
      decades. Hemorrhage continues to be a major cause of death in both the civilian
      and military trauma population, and survival depends on adequacy of hemorrhage
      control and resuscitation between onset of bleeding and arrival at a medical
      treatment facility. The terms far-forward and austere are defined, respectively,
      as the environment where professional health care providers normally do not
      operate and a setting in which basic equipment and capabilities necessary for
      resuscitation are often not available. The relative austerity of a treatment
      setting may be a function of timing rather than just location, as life-saving
      interventions must be performed quickly before hemorrhagic shock becomes
      irreversible. Fresh whole blood transfusions in the field may be a feasible life
      saving procedure when facing significant hemorrhage. 

PMID- 25757010
TI  - Ice Hockey Summit II: zero tolerance for head hits and fighting.
AB  - This study aimed to present currently known basic science and on-ice influences
      of sport-related concussion (SRC) in hockey, building upon the Ice Hockey Summit
      I action plan (2011) to reduce SRC. The prior summit proceedings included an
      action plan intended to reduce SRC. As such, the proceedings from Summit I served
      as a point of departure for the science and discussion held during Summit II
      (Mayo Clinic, Rochester, MN, October 2013). Summit II focused on (1) Basic
      Science of Concussions in Ice Hockey: Taking Science Forward, (2) Acute and
      Chronic Concussion Care: Making a Difference, (3) Preventing Concussions via
      Behavior, Rules, Education, and Measuring Effectiveness, (4) Updates in
      Equipment: Their Relationship to Industry Standards, and (5) Policies and Plans
      at State, National, and Federal Levels To Reduce SRC. Action strategies derived
      from the presentations and discussion described in these sectors were voted on
      subsequently for purposes of prioritization. The following proceedings include
      the knowledge and research shared by invited faculty, many of whom are health
      care providers and clinical investigators. The Summit II evidence-based action
      plan emphasizes the rapidly evolving scientific content of hockey SRC. It
      includes the most highly prioritized strategies voted on for implementation to
      decrease concussion. The highest-priority action items identified from the Summit
      include the following: (1) eliminate head hits from all levels of ice hockey, (2)
      change body checking policies, and (3) eliminate fighting in all amateur and
      professional hockey.

PMID- 25757011
TI  - HIF-2alpha attenuates lymphangiogenesis by up-regulating IGFBP1 in hepatocellular
      carcinoma.
AB  - BACKGROUND INFORMATION: Tumour-associated lymphangiogenesis was identified as an
      important clinical determinant for the prognosis of hepatocellular carcinoma
      (HCC) and significantly influences patient survival. However, in this context,
      little is known about regulation of lymphangiogenesis by hypoxia-inducible
      factors (HIF). In HCC, mainly HIF-1alpha was positively correlated with lymphatic
      invasion and metastasis, whereas a defined role of HIF-2alpha is missing.
      RESULTS: We created a stable knockdown (k/d) of HIF-1alpha and HIF-2alpha in
      HepG2 cells and generated co-cultures of HepG2 spheroids with embryonic bodies.
      This constitutes an in vitro tumour model mimicking the cancer microenvironment
      and allows addressing the role of distinct HIF isoforms in regulating HCC
      lymphangiogenesis. In co-cultures with a HIF-2alpha k/d, lymphangiogenesis was
      significantly increased, whereas the k/d of HIF-1alpha showed no effect. The HIF
      2alpha-dependent lymphangiogenic phenotype was confirmed in vivo using matrigel
      plug assays with supernatants of HIF-2alpha k/d HepG2 cells. We identified and
      verified insulin-like growth factor binding protein 1 (IGFBP1) as a HIF-2alpha
      target gene. The potential of HepG2 cells to induce lymphangiogenesis in two
      independent functional assays was significantly enhanced either by a k/d of HIF
      2alpha or by silencing IGFBP1. Moreover, we confirmed IGF as a potent pro
      lymphatic growth factor with IGFBP1 being its negative modulator. CONCLUSIONS: We
      propose that HIF-2alpha acts as an important negative regulator of hepatic
      lymphangiogenesis in vitro and in vivo by inducing IGFBP1 and thus, interfering
      with IGF signalling. Therefore, HIF-2alpha may constitute a critical target in
      HCC therapy.

PMID- 25757013
TI  - Eyelid sporotrichosis: Unique clinical findings in 72 patients.
AB  - Sporotrichosis on the eyelids is uncommon and has been rarely reported. As the
      largest series of 72 adults and children with eyelid sporotrichosis from Jilin
      Province in China, this study provides useful information for the improved
      diagnosis and treatment of sporotrichosis. 

PMID- 25757012
TI  - Genome-wide association study (GWAS) for growth rate and age at sexual maturation
      in Atlantic salmon (Salmo salar).
AB  - Early sexual maturation is considered a serious drawback for Atlantic salmon
      aquaculture as it retards growth, increases production times and affects flesh
      quality. Although both growth and sexual maturation are thought to be complex
      processes controlled by several genetic and environmental factors, selection for
      these traits has been continuously accomplished since the beginning of Atlantic
      salmon selective breeding programs. In this genome-wide association study (GWAS)
      we used a 6.5K single-nucleotide polymorphism (SNP) array to genotype ~ 480
      individuals from the Cermaq Canada broodstock program and search for SNPs
      associated with growth and age at sexual maturation. Using a mixed model approach
      we identified markers showing a significant association with growth, grilsing
      (early sexual maturation) and late sexual maturation. The most significant
      associations were found for grilsing, with markers located in Ssa10, Ssa02,
      Ssa13, Ssa25 and Ssa12, and for late maturation with markers located in Ssa28,
      Ssa01 and Ssa21. A lower level of association was detected with growth on Ssa13.
      Candidate genes, which were linked to these genetic markers, were identified and
      some of them show a direct relationship with developmental processes, especially
      for those in association with sexual maturation. However, the relatively low
      power to detect genetic markers associated with growth (days to 5 kg) in this
      GWAS indicates the need to use a higher density SNP array in order to overcome
      the low levels of linkage disequilibrium observed in Atlantic salmon before the
      information can be incorporated into a selective breeding program.

PMID- 25757014
TI  - Microsurgical resection of a complex anterior choroidal arteriovenous
      malformation via the transventricular transchoroidal approach: 3-dimensional
      operative video.

PMID- 25757015
TI  - Correspondence: Obituary, Hugo V. Rizzoli, MD, FACS.

PMID- 25757016
TI  - Infants' statistical learning: 2- and 5-month-olds' segmentation of continuous
      visual sequences.
AB  - Past research suggests that infants have powerful statistical learning abilities;
      however, studies of infants' visual statistical learning offer differing accounts
      of the developmental trajectory of and constraints on this learning. To elucidate
      this issue, the current study tested the hypothesis that young infants'
      segmentation of visual sequences depends on redundant statistical cues to
      segmentation. A sample of 20 2-month-olds and 20 5-month-olds observed a
      continuous sequence of looming shapes in which unit boundaries were defined by
      both transitional probability and co-occurrence frequency. Following habituation,
      only 5-month-olds showed evidence of statistically segmenting the sequence,
      looking longer to a statistically improbable shape pair than to a probable pair.
      These results reaffirm the power of statistical learning in infants as young as 5
      months but also suggest considerable development of statistical segmentation
      ability between 2 and 5 months of age. Moreover, the results do not support the
      idea that infants' ability to segment visual sequences based on transitional
      probabilities and/or co-occurrence frequencies is functional at the onset of
      visual experience, as has been suggested previously. Rather, this type of
      statistical segmentation appears to be constrained by the developmental state of
      the learner. Factors contributing to the development of statistical segmentation
      ability during early infancy, including memory and attention, are discussed.

PMID- 25757019
TI  - Characterization of metastatic angiomatoid fibrous histiocytoma.
AB  - Angiomatoid fibrous histiocytoma (AFH) is a soft-tissue tumor of low-grade
      malignancy and uncommon metastatic behavior. In this study, we describe the
      clinical findings of a metastatic case of AFH in the pelvis. In addition, we
      characterize 16 patients in the literature with AFH who metastasized over the
      last 4 decades. The time of appearance of metastases varied substantially and was
      reported 5 months to 16 years after primary tumor resection. Nine patients
      metastasized to lymph nodes. Excision of metastatic lymph nodes was usually
      curative. Pulmonary metastases were associated with fatal outcome. Long-term
      monitoring should be considered in patients with AFH. 

PMID- 25757017
TI  - The lysine acetyltransferase activator Brpf1 governs dentate gyrus development
      through neural stem cells and progenitors.
AB  - Lysine acetylation has recently emerged as an important post-translational
      modification in diverse organisms, but relatively little is known about its roles
      in mammalian development and stem cells. Bromodomain- and PHD finger-containing
      protein 1 (BRPF1) is a multidomain histone binder and a master activator of three
      lysine acetyltransferases, MOZ, MORF and HBO1, which are also known as KAT6A,
      KAT6B and KAT7, respectively. While the MOZ and MORF genes are rearranged in
      leukemia, the MORF gene is also mutated in prostate and other cancers and in four
      genetic disorders with intellectual disability. Here we show that forebrain
      specific inactivation of the mouse Brpf1 gene causes hypoplasia in the dentate
      gyrus, including underdevelopment of the suprapyramidal blade and complete loss
      of the infrapyramidal blade. We trace the developmental origin to compromised
      Sox2+ neural stem cells and Tbr2+ intermediate neuronal progenitors. We further
      demonstrate that Brpf1 loss deregulates neuronal migration, cell cycle
      progression and transcriptional control, thereby causing abnormal morphogenesis
      of the hippocampus. These results link histone binding and acetylation control to
      hippocampus development and identify an important epigenetic regulator for
      patterning the dentate gyrus, a brain structure critical for learning, memory and
      adult neurogenesis. 

PMID- 25757018
TI  - Tolerogenic modulation of the immune response by oligoglycerol- and polyglycerol
      peptide conjugates.
AB  - Peptide-based therapy is a promising strategy for antigen-specific
      immunosuppression to treat or even heal autoimmune diseases with significantly
      reduced adverse effects compared to conventional therapies. However, there has
      been no major success due to the drawbacks of native peptides, i.e., limited
      bioavailability. Considering the importance and limitations of peptide-based
      therapies for treatment of autoimmune diseases, we designed and constructed
      oligoglycerol (OG)- and polyglycerol (PG)-based peptide conjugates. They were
      evaluated for their biological activity (in vitro and in vivo), bioavailability,
      and tolerogenic potential. Among the OG- and PG-peptide constructs, PG-peptide
      constructs exhibited an extended bioavailability compared to OG-peptide
      constructs and unconjugated peptide. Interestingly, size, structure, and linker
      chemistry played a critical role for the tolerogenic capacity of the constructs.
      The PG-peptide construct bound via an ester linkage was the most tolerogenic
      conjugate, while the PG-peptide construct bound via an amide induced stronger
      proliferation, but also higher TNF production and lower frequencies of Foxp3(+)
      regulatory T-cells. Therefore, we conclude that PG-peptide conjugates bound via
      an ester linkage are not only promising candidates for tolerogenic vaccination,
      but also open a new avenue toward the application of peptides for the treatment
      of autoimmune diseases. 

PMID- 25757020
TI  - Adolescent and Young Adult (AYA) Oncology in the United States: A Specialty in
      Its Late Adolescence.
AB  - Over the last 30 years, it has become apparent that oncology patients ages 15 to
      39 have not reaped the same rewards of improved survival that we have seen in
      younger and older patients. As a result, in 2006 the Adolescent and Young Adult
      (AYA) Oncology Progress Review Group convened and examined the factors that
      impact the care of the 70,000 new cases per year (approximately 7% of all new
      cases) in the United States and published their findings. The reasons for
      inferior survival gains are of course multiple and include the settings in which
      patients are cared for, clinical trial enrollment, insurance coverage, varied
      treatment of sarcomas, varied treatment of acute lymphoblastic leukemia, the
      psychosocial impact of cancer and cancer survivorship. A new area of a yet-to-be
      completely defined subspecialty was born out of this meeting: AYA oncology. As a
      medical community we realized that these patients do not fit neatly into the
      pediatric nor adult world and, therefore, require a unique approach which many
      individuals, oncology centers, advocacy groups, and cooperative trial groups have
      started to address. This group of dedicated providers and advocates has made
      strides but there is still much work to be done on the local, national, and
      international level to make up for shortcomings in the medical system and improve
      outcomes. We review key components of AYA cancer care in 2015 that all providers
      should be aware of, how far we have come, where this movement is headed, and the
      obstacles that continue to stand in the way of better cure rates and quality of
      life after cure for this unique group of patients. Like an adolescent maturing
      into adulthood, this movement has learned from the past and is focused on moving
      into the future to achieve its goals. 

PMID- 25757021
TI  - Institutional adherence to cardiovascular risk factor screening guidelines for
      young survivors of acute lymphoblastic leukemia.
AB  - Survivors of acute lymphoblastic leukemia have increased risk for long-term
      cardiovascular complications. Early identification of cardiovascular risk factors
      (CVRF) may allow for effective interventions. In this retrospective cohort study
      of 194 patients at Children's Hospital Los Angeles, we investigated CVRF
      screening practices in an established childhood cancer survivorship program
      relative to both the Children's Oncology Group (COG) Long-Term Follow-Up
      Guidelines and American Academy of Pediatrics (AAP) recommendations. CVRF
      screening practices met COG but not the more stringent AAP recommendations,
      particularly in areas of dyslipidemia and diabetes screening. Implications of our
      findings are discussed. 

PMID- 25757023
TI  - Vincristine-associated neurological morbidity in the treatment of hepatoblastoma.
AB  - Chemotherapy is an essential component of therapy for infants and children with
      hepatoblastoma. Vincristine has been a mainstay of chemotherapeutic regimens used
      by North American cooperative groups, based on indirect evidence of benefit and
      an assumption of minimal added toxicity. European cooperative group trials have
      reported comparable survival rates using regimens that omit vincristine. Further
      examination of the risk and benefit profile of vincristine relevant to
      hepatoblastoma clinical care paradigms is thus warranted. We evaluated the
      incidence of vincristine-related sensorimotor peripheral, autonomic, and cranial
      nerve neurological morbidities in 45 consecutive hepatoblastoma patients treated
      at our institution. Data suggest an increased risk of vincristine-associated
      neuropathic grade 2 and 3 events (neuropathic pain and gross motor impairment) in
      children ages 24 months old or younger, and particularly in children born
      prematurely. Formal prospective investigation of the relative risks and benefits
      of vincristine in hepatoblastoma treatment is warranted to assess the value of
      continued use of vincristine in this patient population. 

PMID- 25757022
TI  - Very late relapse of bilateral retinoblastoma.
AB  - Retinoblastoma usually recurs within the first few years after treatment
      completion. We report a rare case of very late relapse in a 6-month-old girl who
      was diagnosed with bilateral retinoblastoma. The patient achieved first remission
      after treatment with neoadjuvant chemotherapy, enucleation of the right eye,
      local laser therapy of the left eye, and adjuvant chemotherapy. Extraocular
      relapse with multiple metastases occurred 13 years and 8 months after treatment.
      The patient is currently in second complete remission after receiving high-dose
      chemotherapy and autologous stem cell transplantation. In conclusion, long-term
      follow-up is needed for early detection of recurrent retinoblastoma. 

PMID- 25757024
TI  - Defining and distinguishing treatment abandonment in patients with cancer.
AB  - Cancer management requires accurate identification of the causes of treatment
      failure followed by cause-specific interventions. One cause of treatment failure
      that has received too little attention is abandonment of treatment. Abandonment
      includes 2 key elements: (1) failing to complete therapy for a disease that could
      be cured or definitively controlled, and (2) missing all treatment for a
      sustained time period to an extent that impacts the ability to cure or
      definitively control the disease. In this Historical Insight paper, we analyze
      historic and current terminology used to describe treatment abandonment in
      patients and provide a framework to distinguish it from nonadherence and loss to
      follow-up. 

PMID- 25757025
TI  - Colostomy for Perianal Sepsis With Ecthyma Gangrenosum in Immunocompromised
      Children.
AB  - BACKGROUND: Perianal sepsis with ecthyma gangrenosum is a severe and potentially
      mutilating complication in immunocompromised children. Therapies include
      antimicrobial treatment, incision and drainage, generous tissue debridement, and
      skin transplantation. PROCEDURE: We describe 3 children with acute lymphoblastic
      leukemia having sepsis with Pseudomonas aeruginosa in febrile neutropenia and
      severe perianal infections treated relatively early with a protective colostomy.
      Indications for colostomy were nonhealing wounds, and ceaseless pain. RESULTS:
      All patients showed a rapid reduction of pain. Complete wound healing was seen in
      2 patients, and considerable pain reduction and increased quality of life were
      seen in a third patient during palliative care. CONCLUSIONS: These results
      suggest that a protective colostomy should be considered early in the management
      of immunocompromised children with ecthyma gangrenosum.

PMID- 25757026
TI  - Right iliac fossa pain: appendicitis is not always the answer.

PMID- 25757027
TI  - A gamma/delta T-cell receptor prolymphocytic leukemia and CD4-/CD8- double
      negative immunophenotype in a pediatric patient.
AB  - T-cell prolymphocytic leukemia is a very rare neoplasm, peaking in the seventh
      decade. An extensive search failed to find any report of this malignancy in the
      pediatric population. The malignant cell is morphologically characterized by a
      high nucleocytopasmic ratio, condensed chromatin, a single nucleolus, and
      nongranular basophilic cytoplasm. Cells are usually positive for the alpha/beta
      and only rarely to the gamma/delta T-cell receptors. Most patients follow an
      aggressive clinical course, only some respond to anti-CD52. We present a 6-year
      old boy with T-cell prolymphocytic leukemia. The malignant cells expressed a
      postthymic immunophenotype (CD4/CD8) and positivity for the gamma/delta T-cell
      receptors. The child died after 8 months despite aggressive chemotherapy, anti
      CD52, and an allogeneic bone marrow transplant. 

PMID- 25757028
TI  - Dermatopathologists' concerns and challenges with clinical information in the
      skin biopsy requisition form: a mixed-methods study.
AB  - BACKGROUND: Communication failures between clinicians and dermatopathologists are
      prevalent. Our primary objective was to characterize the concerns and challenges
      of dermatopathologists posed by incomplete or inaccurate clinical information in
      the skin biopsy requisition form. METHODS: An explanatory sequential, mixed
      methods study design comprised of a survey sent to 1103 members of the American
      Society of Dermatopathology (ASDP), followed by two focus group sessions.
      RESULTS: A total of 54% (598/1103) of dermatopathologists completed the
      questionnaire. Most dermatopathologists (80%; 436/548) viewed their roles to be
      providers of histopathological diagnosis and a report that is clinically
      meaningful. Paper or electronic requisition forms were the most common
      communication method (85%; 458/541) and were associated with the highest rates of
      dissatisfaction in 36% (193/537) of respondents. Inadequacy of specimens emerged
      as an important factor influencing judgment of the quality of provided clinical
      information. 44.7% (261/584) of dermatopathologists spent 30 minutes or more on
      average every day searching for relevant clinical information to assist with
      their histopathologic interpretation. CONCLUSION: ASDP dermatopathologists
      expressed significant dissatisfaction with the quality of clinical information in
      the requisition form and the time spent gathering information necessary for
      accurate, timely and clinically meaningful diagnosis. These findings have
      implications for the quality, safety and efficiency of dermatologic care.

PMID- 25757029
TI  - Overexpression and optimization of glutamate decarboxylase in Lactobacillus
      plantarum Taj-Apis362 for high gamma-aminobutyric acid production.
AB  - Gamma-aminobutyric acid (GABA) is an important bioactive compound biosynthesized
      by microorganisms through decarboxylation of glutamate by glutamate decarboxylase
      (GAD). In this study, a full-length GAD gene was obtained by cloning the template
      deoxyribonucleic acid to pTZ57R/T vector. The open reading frame of the GAD gene
      showed the cloned gene was composed of 1410 nucleotides and encoded a 469 amino
      acids protein. To improve the GABA-production, the GAD gene was cloned into
      pMG36e-LbGAD, and then expressed in Lactobacillus plantarum Taj-Apis362 cells.
      The overexpression was confirmed by SDS-PAGE and GAD activity, showing a 53 KDa
      protein with the enzyme activity increased by sevenfold compared with the
      original GAD activity. The optimal fermentation conditions for GABA production
      established using response surface methodology were at glutamic acid
      concentration of 497.973 mM, temperature 36 degrees C, pH 5.31 and time 60 h.
      Under the conditions, maximum GABA concentration obtained (11.09 mM) was
      comparable with the predicted value by the model at 11.23 mM. To our knowledge,
      this is the first report of successful cloning (clone-back) and overexpression of
      the LbGAD gene from L. plantarum to L. plantarum cells. The recombinant
      Lactobacillus could be used as a starter culture for direct incorporation into a
      food system during fermentation for production of GABA-rich products. 

PMID- 25757030
TI  - Study on the distribution and elimination of the new hormone irisin in vivo: new
      discoveries regarding irisin.
AB  - Irisin is a newly discovered factor that is secreted by skeletal muscle and plays
      an important role in the homeostasis and metabolism of energy balance. This study
      used irisin radiolabeled with (125)I and small-animal SPECT/CT imaging to
      investigate the metabolic elimination and distribution of irisin in vivo. Irisin
      was labeled with (125)I using the Iodogen method. Small-animal SPECT/CT imaging
      was performed on C57/B16 mice at 15, 30, 60, 120, and 240 min after receiving a
      tail vein injection, and the radioactive distribution in the organs of mice was
      determined at 15, 60, and 120 min. Small-animal SPECT/CT imaging revealed the
      highest level of radioactivity in the gallbladder followed by the liver and
      kidney. Radioactivity decreased gradually with time in all organs. The
      radioactive distribution in the mice organs also showed that the highest %ID/g
      was in the gallbladder followed by the kidney and liver, and decreased gradually
      with time. The radioactivity in the gastric system reached its highest level at
      60 min. Finally, our study showed the metabolic clearance of (125)I-irisin is
      achieved primarily through the hepatobiliary and renal system and provided the
      basis for the clinical application of irisin. 

PMID- 25757031
TI  - Detailed monitoring of a small but recovering population reveals sublethal
      effects of disease and unexpected interactions with supplemental feeding.
AB  - Infectious diseases are widely recognized to have substantial impact on wildlife
      populations. These impacts are sometimes exacerbated in small endangered
      populations, and therefore, the success of conservation reintroductions to aid
      the recovery of such species can be seriously threatened by outbreaks of
      infectious disease. Intensive management strategies associated with conservation
      reintroductions can further compound these negative effects in such populations.
      Exploring the sublethal effects of disease outbreaks among natural populations is
      challenging and requires longitudinal, individual life-history data on patterns
      of reproductive success and other indicators of individual fitness. Long-term
      monitoring data concerning detailed reproductive information of the reintroduced
      Mauritius parakeet (Psittacula echo) population collected before, during and
      after a disease outbreak was investigated. Deleterious effects of an outbreak of
      beak and feather disease virus (BFDV) were revealed on hatch success, but these
      effects were remarkably short-lived and disproportionately associated with
      breeding pairs which took supplemental food. Individual BFDV infection status was
      not predicted by any genetic, environmental or conservation management factors
      and was not associated with any of our measures of immune function, perhaps
      suggesting immunological impairment. Experimental immunostimulation using the PHA
      (phytohaemagglutinin assay) challenge technique did, however, provoke a
      significant cellular immune response. We illustrate the resilience of this
      bottlenecked and once critically endangered, island-endemic species to an
      epidemic outbreak of BFDV and highlight the value of systematic monitoring in
      revealing inconspicuous but nonetheless substantial ecological interactions. Our
      study demonstrates that the emergence of such an infectious disease in a
      population ordinarily associated with increased susceptibility does not
      necessarily lead to deleterious impacts on population growth and that negative
      effects on reproductive fitness can be short-lived. 

PMID- 25757032
TI  - A tailored biocatalyst achieved by the rational anchoring of imidazole groups on
      a natural polymer: furnishing a potential artificial nuclease by sustainable
      materials engineering.
AB  - Foreseeing the development of artificial enzymes by sustainable materials
      engineering, we rationally anchored reactive imidazole groups on gum arabic, a
      natural biocompatible polymer. The tailored biocatalyst GAIMZ demonstrated
      catalytic activity (>10(5)-fold) in dephosphorylation reactions with recyclable
      features and was effective in cleaving plasmid DNA, comprising a potential
      artificial nuclease. 

PMID- 25757033
TI  - One-step breaking and separating emulsion by tungsten oxide coated mesh.
AB  - Tungsten oxide coated mesh has been fabricated by a simple and inexpensive
      method. This coated mesh has a dual structure on the surface, consisting of
      microscale "flower" and nanoscale acicular crystal as the "petal". Combining the
      micro/nano structure of the surface and the native hydrophilic property of
      tungsten oxide, the coated mesh shows special wettability: superhydrophilic in
      air and superoleophobic under water. Because of the special wettability, such a
      mesh can be used to separate oil/water mixtures as well as emulsions. Attributed
      to the good water adsorption capacity of tungsten oxide, the abundant grooves of
      the micro/nanostructure, and the microsized pores of the surface, this coated
      mesh can accomplish the demulsification process and the separation process in one
      single-step, and no further post treatment is needed. As an "emulsion breaker and
      separator", this kind of mesh gives another idea of emulsion separation, which
      has prospective application in industrial fields such as water treatment and
      petroleum refining. 

PMID- 25757034
TI  - Advanced mutasynthesis studies on the natural alpha-pyrone antibiotic myxopyronin
      from Myxococcus fulvus.
AB  - Myxopyronin is a natural alpha-pyrone antibiotic from the soil bacterium
      Myxococcus fulvus Mx f50. Myxopyronin inhibits bacterial RNA polymerase (RNAP) by
      binding to a part of the enzyme not targeted by the clinically used rifamycins.
      This mode of action makes myxopyronins promising molecules for the development of
      novel broad-spectrum antibacterials. We describe the derivatization of
      myxopyronins by an advanced mutasynthesis approach as a first step towards this
      goal. Site-directed mutagenesis of the biosynthetic machinery was used to block
      myxopyronin biosynthesis at different stages. The resulting mutants were fed with
      diverse precursors that mimic the biosynthetic intermediates to restore
      production. Mutasynthon incorporation and production of novel myxopyronin
      derivatives were analyzed by HPLC-MS/MS. This work sets the stage for accessing
      numerous myxopyronin derivatives, thus significantly expanding the chemical space
      of f alpha-pyrone antibiotics. 

PMID- 25757035
TI  - Cyclic tetramers of a five-membered palladacycle based on a head-to-tail-linked
      isocyanate dimer and their reactivity in cyclotrimerization of isocyanates.
AB  - Reactions of [Pd(styrene)(PR3)2], generated from trans-[PdEt2(PR3)2] and styrene,
      with 2 equiv. of benzyl isocyanate in THF at room-temperature afforded unusual
      cyclic Pd-tetramers of five-membered rings consisting of organic isocyanate
      dimers and palladium, [Pd(PR3){-C(O)N(R)C(O)N(R)-}]4 (PR3 = PMe3, ; PR3 = PMe2Ph,
      ). Additionally, a cyclic trimer, (RNCO)3, (R = benzyl) was produced as a
      catalytic product. Treatment of the cyclic tetramer () with 4 equiv. of chelated
      phosphine, such as (1,2-bis(diethylphosphino)ethane) (DEPE) or (1,2
      bis(dimethylphosphino)ethane) (DMPE), readily caused conversion to a
      metallacyclic cis-form, [Pd{N(R)C(O)N(R)C(O)}(P ~ P)] (P ~ P = DEPE, ; P ~ P =
      DMPE, ) in quantitative yields. In contrast, reactions of Pd(0)-PR3 with 2 equiv.
      of Ar-NCO (Ar = Ph, p-tolyl, p-ClC6H4) afforded metallacyclic complexes having a
      dimeric isocyanato moiety, cis-[Pd{C(O)N(Ar)-C(O)N(Ar)}(PR3)2] (PR3 = PMe3 Ar =
      C6H5, ; p-MeC6H4, ; p-Cl-C6H4, ; PR3 = PMe2Ph, Ar = p-Cl-C6H4, ). Treatment of
      the palladacyclic complex () with an equimolar amount of chelated phosphine such
      as DEPE readily caused conversion to a palladacyclic cis-form,
      [Pd{N(Ar)C(O)N(Ar)C(O)}(DEPE)], in quantitative yield. The catalytic
      cyclotrimerization of benzyl isocyanate to [Pd(styrene)(PMe3)2] was achieved by
      varying the molar ratio of R-NCO (R = benzyl). In addition, catalytic
      cyclotrimerization was performed from the five-membered palladacyclic complexes
      or the Pd(0)-PR3 complex with excess Ar-NCO. 

PMID- 25757036
TI  - Comparison of 368 patients undergoing surgery for lumbar degenerative
      spondylolisthesis from the SPORT trial with 955 from the NSQIP database.
AB  - STUDY DESIGN: Retrospective cohort. OBJECTIVE: To compare demographics and
      perioperative outcomes between the Spine Patient Outcomes Research Trial (SPORT)
      lumbar degenerative spondylolisthesis arm and a similar population from the
      National Surgical Quality Improvement Program (NSQIP) database. SUMMARY OF
      BACKGROUND DATA: SPORT is a well-known surgical trial that investigated the
      benefits of surgical versus nonsurgical treatment in patients with various lumbar
      pathologies. However, the external validity of SPORT demographics and outcomes
      has not been fully established. METHODS: Surgical degenerative spondylolisthesis
      cases were identified from NSQIP between 2010 and 2012. This population was then
      compared with the SPORT degenerative spondylolisthesis study. These comparisons
      were based on published data from SPORT and included analyses of demographics,
      perioperative factors, and complications. RESULTS: The 368 surgical patients with
      degenerative spondylolisthesis in SPORT were compared with 955 patients
      identified in NSQIP. Demographic comparisons were as follows: average age and
      race (no difference; P > 0.05 for each), sex (9.1% more female patients in SPORT;
      P = 0.002), smoking status (6.6% more smokers in NSQIP; P = 0.002), and average
      body mass index (1.1 kg/m greater in NSQIP; P = 0.005). Larger differences were
      noted in what surgical procedure was performed (P < 0.001), with the most notable
      difference being that the NSQIP population was much more likely to include
      interbody fusion than the SPORT population (52.4% vs. 12.5%). Most perioperative
      factors and complication rates were similar, including average operative time,
      wound infection, wound dehiscence, postoperative transfusion, and postoperative
      mortality (no differences; P > 0.05 for each). Average length of stay was shorter
      in NSQIP compared with SPORT (3.7 vs. 5.8 d; P = 0.042). CONCLUSION: Though
      important differences in the distribution of surgical procedures were identified,
      this study supports the greater generalizability of the surgical SPORT
      degenerative spondylolisthesis study based on similar demographics and
      perioperative outcomes when compared with patients from the NSQIP database. LEVEL
      OF EVIDENCE: 3.

PMID- 25757037
TI  - Delayed surgery after acute traumatic central cord syndrome is associated with
      reduced mortality.
AB  - STUDY DESIGN: A retrospective study of surgically treated patients with acute
      traumatic central cord syndrome (ATCCS) from the National Trauma Data Bank
      Research Data Set. OBJECTIVE: To determine the association of time to surgery,
      pre-existing comorbidities, and injury severity on mortality and adverse events
      in surgically treated patients with ATCCS. SUMMARY OF BACKGROUND DATA: Although
      earlier surgery has been shown to be beneficial for other spinal cord injuries,
      the literature is mixed regarding the appropriate timing of surgery after ATCCS.
      Traditionally, this older population has been treated with delayed surgery
      because medical optimization is often indicated preoperatively. METHODS:
      Surgically treated patients with ATCCS in the National Trauma Data Bank Research
      Data Set from 2011 and 2012 were identified. Time to surgery, Charlson
      Comorbidity Index, and injury severity scores were tested for association with
      mortality, serious adverse events, and minor adverse events using multivariate
      logistic regression. RESULTS: A total of 1060 patients with ATCCS met inclusion
      criteria. After controlling for pre-existing comorbidity and injury severity,
      delayed surgery was associated with a decreased odds of inpatient mortality (odds
      ratio = 0.81, P = 0.04), or a 19% decrease in odds of mortality with each 24-hour
      increase in time until surgery. The association of time to surgery with serious
      adverse events was not statistically significant (P = 0.09), whereas time to
      surgery was associated with increased odds of minor adverse events (odds ratio =
      1.06, P < 0.001). CONCLUSION: Although the potential neurological effect of
      surgical timing for patients with ATCCS remains controversial, the decreased
      mortality with delayed surgery suggests that waiting to optimize general health
      and potentially allow for some spinal cord recovery in these patients may be
      advantageous. LEVEL OF EVIDENCE: 3.

PMID- 25757038
TI  - Risk of burnout among early career mental health professionals.
AB  - Burnout is a stress-related syndrome that often affects mental health
      professionals (MHPs) and may have serious consequences on personal well-being as
      well as on the quality of provided psychiatric care. Established literature shows
      a high risk to develop burnout among MHPs. Few data are available on the
      incidence and on the clinical implications of the burnout syndrome in the early
      phases of MHP professional career. We confirmed the presence of burnout among
      early career MHPs: early career psychiatrists showed a lower sense of personal
      accomplishment, while non-medical MHPs tended to have more depersonalization and
      suffered from higher levels of depression. Specific programmes to identify the
      presence of the burnout syndrome and to cope with it should be taught within
      mental health training curricula. Burnout is a stress-related syndrome that often
      affects professionals working in emotionally loaded and highly interpersonal
      environments. Mental health professionals (MHPs) are long known to be at high
      risk to develop the burnout syndrome, but this has rarely been investigated in
      professionals in an early phase of career. The aim of the present study was to
      evaluate the presence of the burnout syndrome and of depressive symptoms among
      early career psychiatrists and 'non-medical' MHPs. One hundred MHPs (including 50
      psychiatrists and 50 non-medical MHPs) were screened for the presence of burnout
      and depression, with the Maslach Burnout Inventory and the Beck Depression
      Inventory - revised, respectively. The relationships of burnout with socio
      demographical and professional characteristics were also explored. We confirmed
      the presence of burnout among both groups of early career MHPs, but psychiatrists
      had a significantly higher degree of emotional exhaustion and a lower sense of
      personal accomplishment, while non-medical MHPs adopted more frequently
      depersonalization as a coping strategy and had higher scores for depression,
      which is associated with higher level of burnout. The risk of developing burnout
      should be properly addressed in training curricula and strategies to overcome it
      should be systematically taught, in order to promote personal well-being and
      efficient team work in mental health settings.

PMID- 25757039
TI  - Does Systolic Blood Pressure Response to Lifestyle Intervention Indicate
      Metabolic Risk and Health-Related Quality-of-Life Improvement Over 1 Year?
AB  - The purpose of this study was to determine whether responders (minimum 4-mm Hg
      reduction of systolic blood pressure [BP]) at 24 weeks) to a 52-week lifestyle
      intervention had greater changes in metabolic risk factors and health-related
      quality of life than nonresponders. Participants (N=126; age, 57.4 [9.1] years)
      had waist circumference (WC), resting BP, glycated hemoglobin, lipids, and
      fitness assessed at baseline and at 12, 24, and 52 months. The 36-item short-form
      survey was administered to assess HRQOL. At baseline, responders had higher
      mental health scores (P=.04) and systolic and diastolic BPs (P<.001) than
      nonresponders. Across 52 weeks, responders also had greater improvements in
      diastolic BP (P<.001), WC (P=.01), and maximal oxygen uptake (P=.04) compared
      with nonresponders. Participants with clinically important changes in systolic BP
      at 24 weeks had greater metabolic improvements across 52 weeks, compared with
      those without clinically important systolic BP changes. 

PMID- 25757041
TI  - Reduced levels of plasma polyunsaturated fatty acids and serum carnitine in
      autistic children: relation to gastrointestinal manifestations.
AB  - BACKGROUND: Gastrointestinal (GI) manifestations are common in autistic children.
      Polyunsaturated fatty acids (PUFAs) and carnitine are anti-inflammatory molecules
      and their deficiency may result in GI inflammation. The relationship between the
      increased frequency of GI manifestations and reduced levels of PUFAs and
      carnitine was not previously investigated in autistic patients. This study was
      the first to investigate plasma levels of PUFAs and serum carnitine in relation
      to GI manifestations in autistic children. METHODS: Plasma levels of PUFAs
      (including linoleic, alphalinolenic, arachidonic "AA" and docosahexaenoic "DHA"
      acids) and serum carnitine were measured in 100 autistic children and 100 healthy
      matched children. RESULTS: Reduced levels of serum carnitine and plasma DHA, AA,
      linolenic and linoleic acids were found in 66%, 62%, 60%, 43% and 38%,
      respectively of autistic children. On the other hand, 54% of autistic patients
      had elevated omega6/omega3 ratio. Autistic patients with GI manifestations (48%)
      had significantly decreased levels of serum carnitine and plasma DHA than
      patients without such manifestations. In addition, autistic patients with GI
      manifestations had significantly increased percentage of reduced serum carnitine
      (91.7%) and plasma DHA levels (87.5%) than patients without such manifestations
      (42.3% and 38.5%, respectively), (P < 0.001 and P < 0.001%, respectively).
      CONCLUSIONS: Reduced levels of plasma DHA and serum carnitine levels may be
      associated with the GI problems in some autistic patients. However, this is an
      initial report, studies are recommended to invesigate whether reduced levels of
      carnitine and DHA are a mere association or have a pathogenic role in GI problems
      in autistic patients.

PMID- 25757042
TI  - In vitro susceptibility patterns of clinically important Trichophyton and
      Epidermophyton species against nine antifungal drugs.
AB  - Despite the common, worldwide, occurrence of dermatophytes, little information is
      available regarding susceptibility profiles against currently available and novel
      antifungal agents. A collection of sixty-eight clinical Trichophyton species and
      Epidermophyton floccosum were previously identified and verified to the species
      level by sequencing the internal transcribed spacer (ITS) regions of rDNA. MICs
      of amphotericin B, fluconazole, itraconazole, voriconazole, posaconazole,
      isavuconazole, terbinafine and MECs of caspofungin and anidulafungin were
      performed based on CLSI M38-A2. The resulting MIC90 s of all strains were, in
      increasing order, as follows: terbinafine (0.063 mg l(-1) ); posaconazole (1 mg
      l(-1) ); isavuconazole and anidulafungin (2 mg l(-1) ); itraconazole,
      voriconazole, amphotericin B, and caspofungin (4 mg l(-1) ) and fluconazole (>64
      mg l(-1) ). These results confirm that terbinafine is an excellent agent for
      treatment of dermatophytosis due to T. rubrum, T. mentagrophytes, T. verrucosum,
      T. schoenleinii and E. floccosum. In addition, the new azoles POS and ISA are
      potentially useful antifungals to treat dermatophytosis. However, the clinical
      effectiveness of these novel antifungals remains to be determined.

PMID- 25757043
TI  - Retinopathy of prematurity: New developments bring concern and hope.
AB  - Blindness from retinopathy of prematurity (ROP) in Australian and New Zealand is
      an uncommon event although 3% of <31 weeks gestation infants receive treatment
      for the disease. New world-wide estimates of the incidence of blindness from ROP
      are much higher than previously at 20 000 children annually. The impact of severe
      ROP can be reduced through good evidence-based care of very preterm infants and
      careful organisation of eye examinations and follow-up services. Recent oxygen
      saturation targeting trial results might mean the adoption of higher targets than
      formerly in very preterm infants and will require vigilance to ensure all
      eligible infants are examined appropriately. A true screening examination for
      acute ROP might involve non-opthalmologists obtaining photographic retinal images
      and remote reading of these. Although treatment with laser gives good outcomes,
      there is interest in intravitreal anti-vascular endothelial factor agents, but
      issues concerning the systemic safety and retinal results of such treatment are
      unresolved. 

PMID- 25757044
TI  - Identification, synthesis, and safety assessment of forchlorfenuron (1-(2-chloro
      4-pyridyl)-3-phenylurea) and its metabolites in kiwifruits.
AB  - Identification and evaluation of safety of forchlorfenuron ((1-(2-chloro-4
      pyridyl)-3-phenylurea)), 1, metabolites after biotransformation in kiwifruit is
      the objective of this study. To elucidate properties of these metabolites, liquid
      chromatography hybrid ion trap time-of-flight mass spectrometry (LC-IT-TOF-MS)
      was applied, with MetID Solution and Formula Predictor Software in positive mode.
      Cytotoxicity of forchlorfenuron and its metabolites were tested through
      sulforhodamine B assays against normal Chinese hamster ovary cells (CHO). As
      deduced from characteristic fragment ions of forchlorfenuron, then confirmed by
      comparison with synthetic standards, as well as characterized by NMR and mass
      spectrometry techniques, results indicate the presence of 4-hydroxyphenyl
      forchlorfenuron, 2, 3-hydroxyphenyl-forchlorfenuron, 3, and forchlorfenuron-4-O
      beta-D-glucoside, 5. Forchlorfenuron (IC50 = 12.12 +/- 2.14 MUM) and 4
      hydroxyphenyl-forchlorfenuron (IC50 = 36.15 +/- 1.59 MUM), exhibits significant
      cytotoxicity against CHO, while 3-hydroxyphenyl-forchlorfenuron and
      forchlorfenuron-4-O-beta-D-glucoside show no cytotoxicity.

PMID- 25757045
TI  - Intragraft regulatory T cells and lung transplant outcomes--we are still at
      square one.

PMID- 25757046
TI  - Stille Catalyst-Transfer Polycondensation Using Pd-PEPPSI-IPr for High-Molecular
      Weight Regioregular Poly(3-hexylthiophene).
AB  - A commercially available palladium N-heterocyclic carbene (Pd-NHC) precatalyst is
      used to initiate chain-growth polymerization of 2-bromo-3-hexyl-5
      trimethylstannylthiophene. The molecular weight of the resultant poly(3
      hexylthiophene) can be modulated (7 to 73 kDa, D = 1.14 to 1.53) by varying the
      catalyst concentration. Mass spectrometry data confirm control over the polymer
      end groups and (1)H NMR spectroscopy reveals that the palladium catalyst is
      capable of "ring-walking". A linear relationship between Mn and monomer
      conversion is observed. Atomic force microscopy and X-ray scattering verify the
      regioregular nature of the resultant polythiophene.

PMID- 25757047
TI  - Synthesis and structural studies of nickel(0) Tetracarbene complexes with the
      introduction of a new four-coordinate geometric index, taudelta.
AB  - The synthesis and characterization of two homoleptic chelating nickel(0)
      tetracarbene complexes are reported. These are the first group 10 M(0) (M = Ni,
      Pd, Pt) tetracarbene complexes. These species have geometries intermediate
      between C2v sawhorse and tetrahedral and show high UV-vis absorption in the 350
      600 nm range, with extinction coefficients (epsilon) between 5600 and 9400 M(-1)
      cm(-1). Density functional theory analysis indicates that this high absorptivity
      is due to metal-to-ligand charge transfer. In order to better describe the
      unusual geometries encountered in these complexes, an adjustment to the popular
      tau4 index for four-coordinate geometries is introduced in order to better
      delineate between sawhorse and distorted tetrahedral geometries. 

PMID- 25757053
TI  - Iron-facilitated oxidative radical decarboxylative cross-coupling between alpha
      oxocarboxylic acids and acrylic acids: an approach to alpha,beta-unsaturated
      carbonyls.
AB  - The first Fe-facilitated decarboxylative cross-coupling reaction between alpha
      oxocarboxylic acids and acrylic acids in aqueous solution has been developed.
      This transformation is characterized by its wide substrate scope and good
      functional group compatibility utilizing inexpensive and easily accessible
      reagents, thus providing an efficient and expeditious approach to an important
      class of alpha,beta-unsaturated carbonyls frequently found in bioactive
      compounds. The synthetic potential of the coupled products is also demonstrated
      in subsequent functionalization reactions. Preliminary mechanism studies suggest
      that a free radical pathway is involved in this process: the generation of an
      acyl radical from alpha-oxocarboxylic acid via the excision of carbon dioxide
      followed by the addition of an acyl radical to the alpha-position of the double
      bond in acrylic acid then delivers the alpha,beta-unsaturated carbonyl adduct
      through the extrusion of another carbon dioxide. 

PMID- 25757054
TI  - An alternative to the Sandmeyer approach to aryl iodides.
AB  - Iodoarenes are important synthons for a wide range of organic transformations.
      Here we report a general strategy to prepare singly iodinated electron-rich
      aromatic compounds through the intermediacy of diaryliodonium salts. This
      process, which incorporates a phase separation that greatly simplifies product
      purification, is an attractive replacement for the Sandmeyer approach to
      iodoarenes that are otherwise difficult to access. 

PMID- 25757055
TI  - Modulation of Splicing by Single-Stranded Silencing RNAs.
AB  - Single-stranded silencing RNAs (ss-siRNAs) are chemically modified single
      stranded oligonucleotides that can function through the cellular RNA interference
      (RNAi) machinery to modulate gene expression. Because their invention is recent,
      few studies have appeared describing their use and the potential of ss-siRNAs as
      a platform for controlling gene expression remains largely unknown. Using
      oligonucleotides to modulate splicing is an important area for therapeutic
      development and we tested the hypothesis that ss-siRNAs targeting splice sites
      might also be capable of directing increased production of therapeutically
      promising protein isoforms. Here we observe that ss-siRNAs alter splicing of
      dystrophin. Altered splicing requires a seed sequence complementarity to the
      target and expression of the RNAi factor argonaute 2. These results demonstrate
      that ss-siRNAs can be used to modulate splicing, providing another option for
      therapeutic development programs that aim to increase production of key protein
      isoforms. Splicing is a classical nuclear process and our data showing that it
      can be modulated through the action of RNA and RNAi factors offers further
      evidence that RNAi can take place in mammalian cell nuclei. 

PMID- 25757056
TI  - Differential Susceptibility of Human Pleural and Peritoneal Mesothelial Cells to
      Asbestos Exposure.
AB  - Malignant mesothelioma (MM) is an aggressive cancer of mesothelial cells of
      pleural and peritoneal cavities. In 85% of cases both pleural and peritoneal MM
      is caused by asbestos exposure. Although both are asbestos-induced cancers, the
      incidence of pleural MM is significantly higher (85%) than peritoneal MM (15%).
      It has been proposed that carcinogenesis is a result of asbestos-induced
      inflammation but it is not clear what contributes to the differences observed
      between incidences of these two cancers. We hypothesize that the observed
      differences in incidences of pleural and peritoneal MM are the result of
      differences in the direct response of these cell types to asbestos rather than to
      differences mediated by the in vivo microenvironment. To test this hypothesis we
      characterized cellular responses to asbestos in a controlled environment. We
      found significantly greater changes in genome-wide expression in response to
      asbestos exposure in pleural mesothelial cells as compared to peritoneal
      mesothelial cells. In particular, a greater response in many common genes (IL-8,
      ATF3, CXCL2, CXCL3, IL-6, GOS2) was seen in pleural mesothelial cells as compared
      to peritoneal mesothelial cells. Unique genes expressed in pleural mesothelial
      cells were mainly pro-inflammatory (G-CSF, IL-1beta, IL-1alpha, GREM1) and have
      previously been shown to be involved in development of MM. Our results are
      consistent with the hypothesis that differences in incidences of pleural and
      peritoneal MM upon exposure to asbestos are the result of differences in
      mesothelial cell physiology that lead to differences in the inflammatory
      response, which leads to cancer.

PMID- 25757057
TI  - Nb-doped rutile TiO2: a potential anode material for Na-ion battery.
AB  - The electrochemical properties of the rutile-type TiO2 and Nb-doped TiO2 were
      investigated for the first time as Na-ion battery anodes. Ti(1-x)Nb(x)O2 thick
      film electrodes without a binder and a conductive additive were prepared using a
      sol-gel method followed by a gas-deposition method. The TiO2 electrode showed
      reversible reactions of Na insertion/extraction accompanied by
      expansion/contraction of the TiO2 lattice. Among the Ti(1-x)Nb(x)O2 electrodes
      with x = 0-0.18, the Ti(0.94)Nb(0.06)O2 electrode exhibited the best cycling
      performance, with a reversible capacity of 160 mA h g(-1) at the 50th cycle. As
      the Li-ion battery anode, this electrode also attained an excellent rate
      capability, with a capacity of 120 mA h g(-1) even at the high current density of
      16.75 A g(-1) (50C). The improvements in the performances are attributed to a 3
      orders of magnitude higher electronic conductivity of Ti(0.94)Nb(0.06)O2 compared
      to that of TiO2. This offers the possibility of Nb-doped rutile TiO2 as a Na-ion
      battery anode as well as a Li-ion battery anode.

PMID- 25757058
TI  - Benchmarking of homogeneous electrocatalysts: overpotential, turnover frequency,
      limiting turnover number.
AB  - In relation to contemporary energy challenges, a number of molecular catalysts
      for the activation of small molecules, mainly based on transition metal
      complexes, have been developed. The time has thus come to develop tools allowing
      the benchmarking of these numerous catalysts. Two main factors of merit are
      addressed. One involves their intrinsic catalytic performances through the
      comparison of "catalytic Tafel plots" relating the turnover frequency to the
      overpotential independently of the characteristics of the electrochemical cell.
      The other examines the effect of deactivation of the catalyst during the course
      of electrolysis. It introduces the notion of the limiting turnover number as a
      second key element of catalyst benchmarking. How these two factors combine with
      one another to control the course of electrolysis is analyzed in detail, leading
      to procedures that allow their separate estimation from measurements of the
      current, the charge passed, and the decay of the catalyst concentration.
      Illustrative examples from literature data are discussed. 

PMID- 25757059
TI  - Autophagy and inflammasome interplay.
AB  - Inflammation is a defensive response of the organism to manage harmful stimuli
      sensed by innate immune cells. The signal alarm is triggered by the recognition
      of pathogen-associated molecular patterns, such as microbial components, or host
      derived damage-associated molecular patterns (DAMPs), namely high-mobility group
      box 1 protein (HMGB1) and purine metabolites, through a set of highly conserved
      receptors in immune cells termed pattern recognition receptors. Among these
      receptors, membrane-associated toll-like receptors (TLRs) and cytosolic
      nucleotide binding and oligomerization domain (nod)-like receptors (NLRs) assume
      particular relevance in the inflammatory process. Once activated, NLRs induce the
      assembly of multiprotein complexes called inflammasomes, leading to production of
      proinflammatory cytokines (e.g., interleukin-1) and induction of inflammatory
      cell death (pyroptosis) through the activation of caspase-1. Although these
      processes intend to protect the body from insults, prolonged or exacerbated
      inflammatory responses associated with inflammasome activation are related to a
      growing number of diseases. Recently, inflammasome activation and autophagy were
      shown to be linked and to mutually influence each other. Therefore, we aim, in
      this review, to discuss the recent evidences concerning the cross talk between
      autophagy and inflammasome activation and its potential roles in disease
      progression. 

PMID- 25757060
TI  - X-linked agammaglobulinemia in two siblings with a novel mutation in the BTK gene
      who presented with polyarticular juvenile idiopathic arthritis.

PMID- 25757063
TI  - Influence of activation protocol on perceived pain during rapid maxillary
      expansion.
AB  - OBJECTIVE: To investigate the influence of two different activation protocols on
      the timing and intensity of pain during rapid maxillary expansion (RME).
      MATERIALS AND METHODS: A total of 112 prepubertal patients (54 males and 58
      females, mean age 11.00 +/- 1.80 years) with constricted maxillary arches
      underwent RME with two different activation protocols (group 1: one
      activation/day; group 2: two activations/day). Patients were provided with a
      numeric rating scale (NRS) and the Faces Pain Scale (FPS) to correctly assess
      their daily pain. RESULTS: Subjects treated with RME at two activations/day
      reported statistically significantly greater amounts of pain than subjects
      treated with RME at one activation/day. Differences related to gender and
      skeletal maturity were found. CONCLUSION: The choice of activation protocol
      influences the perceived pain during RME, and less daily expansion is correlated
      to less pain. Pain reported during RME could be influenced by skeletal maturity
      and gender of the subjects under treatment.

PMID- 25757064
TI  - Remote Giant Multispectral Plasmonic Shifts of Labile Hinged Nanorod Array via
      Magnetic Field.
AB  - We report a remotely mediated and fast responsive plasmonic-magnetic nanorod
      array with extremely large variability in optical appearance (up to 100 nm shifts
      in scattering maxima) and concurrently for multiple wavelengths in a broad range
      from UV-vis to near-infrared (at 450, 550, and 670 nm) with an external magnetic
      field with variable direction. The observed phenomenon demonstrates a rapid, wide
      range response controlled via a noninvasive remote stimulus. The remotely
      controlled system suggested here is a magnetic field-directed assembly of an
      ordered monolayer array of unipolar oriented magnetic-plasmonic nickel-gold
      nanorods flexibly hinged to a sticky substrate. The unique geometry of the mobile
      nanorod array allows for the instant alteration of the surface plasmon polariton
      modes in the gold segment of the controllably tilting nanorods. This design
      demonstrates the utility of hybrid bimetallic nanoparticles and gives a novel
      approach to the design of fast-acting, remotely controlled color-changing
      nanomaterials for sensing and interfacial transport. 

PMID- 25757062
TI  - Myxoma virus and the Leporipoxviruses: an evolutionary paradigm.
AB  - Myxoma virus (MYXV) is the type species of the Leporipoxviruses, a genus of
      Chordopoxvirinae, double stranded DNA viruses, whose members infect leporids and
      squirrels, inducing cutaneous fibromas from which virus is mechanically
      transmitted by biting arthropods. However, in the European rabbit (Oryctolagus
      cuniculus), MYXV causes the lethal disease myxomatosis. The release of MYXV as a
      biological control for the wild European rabbit population in Australia,
      initiated one of the great experiments in evolution. The subsequent coevolution
      of MYXV and rabbits is a classic example of natural selection acting on virulence
      as a pathogen adapts to a novel host species. Slightly attenuated mutants of the
      progenitor virus were more readily transmitted by the mosquito vector because the
      infected rabbit survived longer, while highly attenuated viruses could be
      controlled by the rabbit immune response. As a consequence, moderately attenuated
      viruses came to dominate. This evolution of the virus was accompanied by
      selection for genetic resistance in the wild rabbit population, which may have
      created an ongoing co-evolutionary dynamic between resistance and virulence for
      efficient transmission. This natural experiment was repeated on a continental
      scale with the release of a separate strain of MYXV in France and its subsequent
      spread throughout Europe. The selection of attenuated strains of virus and
      resistant rabbits mirrored the experience in Australia in a very different
      environment, albeit with somewhat different rates. Genome sequencing of the
      progenitor virus and the early radiation, as well as those from the 1990s in
      Australia and Europe, has shown that although MYXV evolved at high rates there
      was no conserved route to attenuation or back to virulence. In contrast, it seems
      that these relatively large viral genomes have the flexibility for multiple
      pathways that converge on a similar phenotype.

PMID- 25757065
TI  - Aven-mediated checkpoint kinase control regulates proliferation and resistance to
      chemotherapy in conventional osteosarcoma.
AB  - Conventional high-grade osteosarcoma is the most common primary bone sarcoma,
      with relatively high incidence in young people. In this study we found that
      expression of Aven correlates inversely with metastasis-free survival in
      osteosarcoma patients and is increased in metastases compared to primary tumours.
      Aven is an adaptor protein that has been implicated in anti-apoptotic signalling
      and serves as an oncoprotein in acute lymphoblastic leukaemia. In osteosarcoma
      cells, silencing Aven triggered G2 cell-cycle arrest; Chk1 protein levels were
      attenuated and ATR-Chk1 DNA damage response signalling in response to
      chemotherapy was abolished in Aven-depleted osteosarcoma cells, while ATM, Chk2
      and p53 activation remained intact. Osteosarcoma is notoriously difficult to
      treat with standard chemotherapy, and we examined whether pharmacological
      inhibition of the Aven-controlled ATR-Chk1 response could sensitize osteosarcoma
      cells to genotoxic compounds. Indeed, pharmacological inhibitors targeting
      Chk1/Chk2 or those selective for Chk1 synergized with standard chemotherapy in 2D
      cultures. Likewise, in 3D extracellular matrix-embedded cultures, Chk1 inhibition
      led to effective sensitization to chemotherapy. Together, these findings
      implicate Aven in ATR-Chk1 signalling and point towards Chk1 inhibition as a
      strategy to sensitize human osteosarcomas to chemotherapy.

PMID- 25757066
TI  - Synthesis of multifunctional plasmonic nanopillar array using soft thermal
      nanoimprint lithography for highly sensitive refractive index sensing.
AB  - A low-cost plasmonic nanopillar array was synthesized using soft thermal
      nanoimprint lithography, and its sensitivity was determined through far-field
      spectroscopic measurements. Its transmission spectrum was highly dependent on the
      refractive index of the surrounding medium, with its sensitivity being 375 nm per
      refractive index unit according to the spectral shift. Moreover, a simple sensor
      whose reflected color changed with a change in the plasma frequency on varying
      the surrounding medium was fabricated. 

PMID- 25757061
TI  - Identification of new respiratory viruses in the new millennium.
AB  - The rapid advancement of molecular tools in the past 15 years has allowed for the
      retrospective discovery of several new respiratory viruses as well as the
      characterization of novel emergent strains. The inability to characterize the
      etiological origins of respiratory conditions, particularly in children, led
      several researchers to pursue the discovery of the underlying etiology of
      disease. In 2001, this led to the discovery of human metapneumovirus (hMPV) and
      soon following that the outbreak of Severe Acute Respiratory Syndrome coronavirus
      (SARS-CoV) promoted an increased interest in coronavirology and the latter
      discovery of human coronavirus (HCoV) NL63 and HCoV-HKU1. Human bocavirus, with
      its four separate lineages, discovered in 2005, has been linked to acute
      respiratory tract infections and gastrointestinal complications. Middle East
      Respiratory Syndrome coronavirus (MERS-CoV) represents the most recent outbreak
      of a completely novel respiratory virus, which occurred in Saudi Arabia in 2012
      and presents a significant threat to human health. This review will detail the
      most current clinical and epidemiological findings to all respiratory viruses
      discovered since 2001.

PMID- 25757067
TI  - Surfactant Driven Post-Deposition Spreading of Aerosols on Complex Aqueous
      Subphases. 2: Low Deposition Flux Representative of Aerosol Delivery to Small
      Airways.
AB  - BACKGROUND: Cystic fibrosis (CF) is associated with the accumulation of
      dehydrated mucus in the pulmonary airways. This alters ventilation and aerosol
      deposition patterns in ways that limit drug delivery to peripheral lung regions.
      We investigated the use of surfactant-based, self-dispersing aerosol carriers
      that produce surface tension gradients to drive two-dimensional transport of
      aerosolized medications via Marangoni flows after deposition on the airway
      surface liquid (ASL). We considered the post-deposition spreading of individual
      aerosol droplets and two-dimensional expansion of a field of aerosol droplets,
      when deposited at low fluxes that are representative of aerosol deposition in the
      small airways. METHODS: We used physically entangled aqueous solutions of
      poly(acrylamide) or porcine gastric mucin as simple ASL mimics that adequately
      capture the full miscibility but slow penetration of entangled macromolecular
      chains of the ASL into the deposited drop. Surfactant formulations were prepared
      with aqueous solutions of nonionic tyloxapol or FS-3100 fluorosurfactant.
      Fluorescein dye served as a model "drug" tracer and to visualize the extent of
      post-deposition spreading. RESULTS: The surfactants not only enhanced post
      deposition spreading of individual aerosol droplets due to localized Marangoni
      stresses, as previously observed with macroscopic drops, but they also produced
      large-scale Marangoni stresses that caused the deposited aerosol fields to expand
      into initially unexposed regions of the subphase. We show that the latter is the
      main mechanism for spreading drug over large distances when aerosol is deposited
      at low fluxes representative of the small airways. The large scale convective
      expansion of the aerosol field drives the tracer (drug mimic) over areas that
      would cover an entire airway generation or more, in peripheral airways, where sub
      monolayer droplet deposition is expected during aerosol inhalation. CONCLUSIONS:
      The results suggest that aerosolized surfactant formulations may provide the
      means to maximize deposited drug uniformity in and access to small airways.

PMID- 25757068
TI  - Photonic crystals cause active colour change in chameleons.
AB  - Many chameleons, and panther chameleons in particular, have the remarkable
      ability to exhibit complex and rapid colour changes during social interactions
      such as male contests or courtship. It is generally interpreted that these
      changes are due to dispersion/aggregation of pigment-containing organelles within
      dermal chromatophores. Here, combining microscopy, photometric videography and
      photonic band-gap modelling, we show that chameleons shift colour through active
      tuning of a lattice of guanine nanocrystals within a superficial thick layer of
      dermal iridophores. In addition, we show that a deeper population of iridophores
      with larger crystals reflects a substantial proportion of sunlight especially in
      the near-infrared range. The organization of iridophores into two superposed
      layers constitutes an evolutionary novelty for chameleons, which allows some
      species to combine efficient camouflage with spectacular display, while
      potentially providing passive thermal protection. 

PMID- 25757070
TI  - Family nurture intervention improves the quality of maternal caregiving in the
      neonatal intensive care unit: evidence from a randomized controlled trial.
AB  - OBJECTIVE: This study assessed the impact of Family Nurture Intervention (FNI) on
      the quality of maternal caregiving behavior (MCB) while in the neonatal intensive
      care unit (NICU). FNI is a randomized controlled trial conducted in a high-acuity
      NICU to facilitate an emotional connection between mothers and their premature
      infants. FNI begins shortly after birth, continues until discharge, and involves
      mother/infant calming sessions that include scent cloth exchange, vocal soothing
      and emotion expression, eye contact, skin-to-skin and clothed holding, and family
      based support sessions. METHODS: Maternal caregiving behavior was coded during a
      single holding and feeding session (~30 min) in the NICU before discharge at
      approximately 36 weeks gestational age (GA). Sixty-five mothers and their
      premature infants (34 male, 31 female; 26-34 wk GA) were included in these
      analyses (FNI, n = 35; standard care [SC], n = 30). RESULTS: Relative to mothers
      in the SC condition, those in the FNI group showed significantly higher quality
      MCB, which remained significant when controlling for birth order, twin status,
      maternal depression, and maternal anxiety. CONCLUSION: This is the first study to
      demonstrate that in-unit MCB can be enhanced by a hospital-based intervention.
      FNI provides a new rationale for integrating nurture-based interventions into
      standard NICU care.

PMID- 25757069
TI  - Relation of Prenatal Methylmercury Exposure from Environmental Sources to
      Childhood IQ.
AB  - BACKGROUND: Although prenatal methylmercury exposure has been linked to poorer
      intellectual function in several studies, data from two major prospective,
      longitudinal studies yielded contradictory results. Associations with cognitive
      deficits were reported in a Faroe Islands cohort, but few were found in a study
      in the Seychelles Islands. It has been suggested that co-exposure to another
      contaminant, polychlorinated biphenyls (PCBs), may be responsible for the
      positive findings in the former study and that co-exposure to nutrients in
      methylmercury-contaminated fish may have obscured and/or protected against
      adverse effects in the latter. OBJECTIVES: We aimed to determine the degree to
      which co-exposure to PCBs may account for the adverse effects of methylmercury
      and the degree to which co-exposure to docosahexaenoic acid (DHA) may obscure
      these effects in a sample of Inuit children in Arctic Quebec. METHODS: IQ was
      estimated in 282 school-age children from whom umbilical cord blood samples had
      been obtained and analyzed for mercury and other environmental exposures.
      RESULTS: Prenatal mercury exposure was related to poorer estimated IQ after
      adjustment for potential confounding variables. The entry of DHA into the model
      significantly strengthened the association with mercury, supporting the
      hypothesis that beneficial effects from DHA intake can obscure adverse effects of
      mercury exposure. Children with cord mercury >= 7.5 MUg/L were four times as
      likely to have an IQ score < 80, the clinical cut-off for borderline intellectual
      disability. Co-exposure to PCBs did not alter the association of mercury with IQ.
      CONCLUSIONS: To our knowledge, this is the first study to document an association
      of prenatal mercury exposure with poorer performance on a school-age assessment
      of IQ, a measure whose relevance for occupational success in adulthood is well
      established. This association was seen at levels in the range within which many
      U.S. children of Asian-American background are exposed.

PMID- 25757071
TI  - Importance of long-term cycles for predicting water level dynamics in natural
      lakes.
AB  - Lakes are disproportionately important ecosystems for humanity, containing 77% of
      the liquid surface freshwater on Earth and comprising key contributors to global
      biodiversity. With an ever-growing human demand for water and increasing climate
      uncertainty, there is pressing need for improved understanding of the underlying
      patterns of natural variability of water resources and consideration of their
      implications for water resource management and conservation. Here we use Bayesian
      harmonic regression models to characterise water level dynamics and study the
      influence of cyclic components in confounding estimation of long-term directional
      trends in water levels in natural Irish lakes. We found that the lakes were
      characterised by a common and well-defined annual seasonality and several inter
      annual and inter-decadal cycles with strong transient behaviour over time.
      Importantly, failing to account for the longer-term cyclic components produced a
      significant overall underestimation of the trend effect. Our findings demonstrate
      the importance of contextualising lake water resource management to the specific
      physical setting of lakes. 

PMID- 25757072
TI  - Adaptive differentiation in seedling traits in a hybrid pine species complex,
      Pinus densata and its parental species, on the Tibetan Plateau.
AB  - Evidence from molecular genetics demonstrates that Pinus densata is a natural
      homoploid hybrid originating from the parent species Pinus tabuliformis and Pinus
      yunnanensis, and ecological selection may have played a role in the speciation of
      P. densata. However, data on differentiation in adaptive traits in the species
      complex are scarce. In this study, we performed a common garden test on 16
      seedling traits to examine the differences between P. densata and its parental
      species in a high altitude environment. We found that among the 16 analyzed
      traits, 15 were significantly different among the species. Pinus tabuliformis had
      much earlier bud set and a relatively higher bud set ratio but poorer seedling
      growth, and P. yunnanensis had opposite responses for the same traits. P. densata
      had the greatest fitness with higher viability and growth rates than the parents.
      The relatively high genetic contribution of seedling traits among populations
      suggested that within each species the evolutionary background is complex. The
      correlations between the seedling traits of a population within a species and the
      environmental factors indicated different impacts of the environment on species
      evolution. The winter temperature is among the most important climate factors
      that affected the fitness of the three pine species. Our investigation provides
      empirical evidence on adaptive differentiation among this pine species complex at
      seedling stages. 

PMID- 25757074
TI  - Application of an organizational evaluation capacity self-assessment instrument
      to different organizations: similarities and lessons learned.
AB  - Organizational evaluation capacity (EC) has received significant attention in the
      evaluation research literature in the past decade. Much of the focus has been on
      defining organizational evaluation capacity, which can be thought of as the
      competencies and structures required to conduct high-quality evaluation studies
      (capacity to do), as well as the organization's ability to integrate evaluation
      findings into its decision-making processes (capacity to use). This paper seeks
      to contribute to this growing body of knowledge through a multiple case study of
      EC across three different organizations (e.g., non-profit, provincial government
      and federal government, herein named sectors); the novelty of this particular
      study is that each case study is based on the use of a common measurement tool
      developed by Bourgeois, Toews, Whynot and Lamarche (2013). The cross-case
      analysis presented in the paper reveals that evaluation capacity tends to be
      higher, both in terms of capacity to do and capacity to use, in organizations
      that have developed systematic mechanisms to institute an evaluation culture
      within their walls. Interestingly, however, we also found that capacity to use
      does not first require capacity to do, as evidenced in the non-profit
      organization under study. 

PMID- 25757073
TI  - A kinetic study of the main guaco metabolites using syrup formulation and the
      identification of an alternative route of coumarin metabolism in humans.
AB  - For decades guaco species have been empirically used for the treatment of
      respiratory diseases. However, studies have shown that the toxic and therapeutic
      effects of the main guaco metabolites are dose-dependent, and none clinical study
      was done to evaluate the behavior of these substances in humans. In this work, a
      pilot study measuring the kinetic profile of the main guaco metabolites was
      performed leading to the knowledge of an alternative route of coumarin metabolism
      in humans. Initial screenings demonstrated that the administration of 60 mL of
      guaco syrup (single dose) did not provide sufficient levels of coumarin (COU), 7
      hydroxycoumarin (7-HCOU), o-coumaric acid (OCA) and kaurenoic acid (KAU). The
      pharmacokinetic parameters were calculated by orally administering 60 mL of guaco
      syrup spiked with 1500 mg of COU. The kinetic study demonstrated that the
      plasmatic levels of 7-HCOU (considered the main metabolite of COU) were 10 times
      lower than the levels of COU, and the kinetic profile of 7-HCOU suggests
      sequential metabolism in the liver with low access of 7-HCOU to the systemic
      circulation. The study also demonstrated that OCA is one of the main bioavailable
      metabolites of COU. Therefore, the hydrolysis of the lactone ring forming a
      carboxylated compound is one of the possible routes of COU metabolism in humans.
      The half-lives of COU, 7-HCOU and OCA were approximately 4.0, 1.0 and 3.0 h,
      respectively and there was evidence that the recommended dosage of guaco syrup
      did not provide sufficient levels of COU, 7-HCOU or OCA to obtain a
      bronchodilation effect. Clinical studies are necessary to prove the efficacy and
      safety of products based on guaco. 

PMID- 25757075
TI  - First principles study of defect formation in thermoelectric zinc antimonide,
      beta-Zn4Sb3.
AB  - Understanding the formation of various point defects in the promising
      thermoelectric material, beta-Zn(4)Sb(3), is crucial for theoretical
      determination of the origins of its p-type behavior and considerations of
      potential n-type dopability. While n-type conductivity has been fleetingly
      observed in Te:ZnSb, there have been no reports, to the best of our knowledge, of
      stable n-type behavior in beta-Zn(4)Sb(3). To understand the origin of this
      difficulty, we investigated the formation of intrinsic point defects in beta
      Zn(4)Sb(3) density functional theory calculations. We found that a negatively
      charged zinc vacancy is the dominant defect in beta-Zn(4)Sb(3), as it is also in
      ZnSb. This explains the unintentional p-type behavior of the material and makes n
      doping very difficult since the formation of the defect becomes more favorable at
      higher Fermi levels, near the conduction band minimum (CBM). We also calculated
      the formation energy of the cation dopants: Li, Na, B, Al, Ga, In, Tl; of these,
      only Li and Na are thermodynamically favorable compared to the acceptor Zn
      vacancy over a range of Fermi levels along the band gap. Further analysis of the
      band structure shows that Li:Zn(4)Sb(3) has a partially occupied topmost valence
      band, making this defect an acceptor so that Li:Zn(4)Sb(3) is indeed a p-type
      thermoelectric material. The introduction of Li, however, creates a more orderly
      and symmetric configuration, which stabilizes the host structure. Furthermore, Li
      reduces the concentration of holes and increases the Seebeck coefficient; hence,
      Li:Zn(4)Sb(3) is more stable and better performing as a thermoelectric material
      than undoped beta-Zn(4)Sb(3).

PMID- 25757076
TI  - The time window for therapy with peptide nanofibers combined with autologous bone
      marrow cells in pigs after acute myocardial infarction.
AB  - BACKGROUND: We previously showed that injection of peptide nanofibers (NF)
      combined with autologous bone marrow mononuclear cells (MNC) immediately after
      coronary artery ligation improves cardiac performance in pigs. To evaluate the
      clinical feasibility, this study was performed to determine the therapeutic time
      window for NF/MNC therapy in acute myocardial infarction (MI). METHODS AND
      RESULTS: A total of 45 adult minipigs were randomly grouped into 7 groups: sham
      or MI plus treatment with NS (normal saline), or NF or MNC alone at 1 day (1D)
      post-MI, or NF/MNC at 1, 4, or 7 days post-MI (N>=6). Cardiac function was
      assessed by echocardiography and ventricular catheterization. Compared with the
      NS control, pigs treated with NF/MNC at 1 day post-MI (NF/MC-1D) had the greatest
      improvement in left ventricle ejection fraction (LVEF; 55.1+/-1.6%; P<0.01 vs.
      NS) 2 months after MI. In contrast, pigs treated with either NF/MNC-4D or NF/MNC
      7D showed 48.9+/-0.8% (P<0.05 vs. NS) and 43.5+/-2.3% (n.s. vs. NS) improvements,
      respectively. The +dP/dt and -dP/dt, infarct size and interstitial collagen
      content were also improved in the NF/MNC-1D and -4D groups but not in the -7D
      group. Mechanistically, MNC quality and the states of systemic inflammation and
      damaged heart tissue influence the therapeutic efficiency of NF/MNC therapy, as
      revealed by another independent study using 16 pigs. CONCLUSIONS: Injection of
      NF/MNC at 1 or 4 days, but not at 7 days post-MI, improves cardiac performance
      and prevents ventricular remodeling, confirming the importance of early
      intervention when using this therapy for acute MI.

PMID- 25757077
TI  - Gold remains an important allergen.

PMID- 25757078
TI  - Gold contact allergy: clues and controversies.
AB  - In 2001, gold was named Contact Allergen of the Year. More than a decade later,
      we continue to face several challenges in defining the role of gold in contact
      allergy. First, interpretation of gold reactions in the setting of epicutaneous
      patch testing may be difficult; in addition to being a common irritant, gold may
      be associated with significantly delayed and persistent reactions. Second,
      although gold compounds are commonly positive on patch testing, clinical
      relevance is relatively low and may be challenging to determine. Third, the
      complex interplay between gold and the human body is still poorly understood. In
      this review, we provide an overview of the literature concerning gold patch test
      positivity and present recommendations for epicutaneous patch testing with gold. 

PMID- 25757079
TI  - Oral allergy syndrome (pollen-food allergy syndrome).
AB  - Oral allergy syndrome (OAS) or pollen-food allergy syndrome (PFS) is a
      hypersensitivity reaction to plant-based foods, manifesting most commonly with
      pruritus of the lips, tongue, and mouth. Unlike simple food allergy, OAS requires
      prior sensitization to a cross-reacting inhalant allergen rather than direct
      sensitization to a specific food protein. In this review, we summarize the
      clinical features and pathophysiology of OAS and provide an overview of known
      pollen-food associations. 

PMID- 25757080
TI  - Patch testing in oral lichenoid lesions of uncertain etiology.
AB  - BACKGROUND: The benefit of patch testing patients with oral lichenoid lesions
      (OLL) is still debated. OBJECTIVE: We assessed the results of patch testing in
      patients with multiple amalgams and multiple OLL, where the etiology of the oral
      mucosal disease was unclear. METHODS: Patients referred from an oral medicine
      clinic were patch tested to the British Society of Cutaneous Allergy standard
      series, dental and materials series, and, in 1 patient, the dental methacrylate
      series also. Patients' responses to amalgam removal were assessed during a mean
      follow-up of 2.6 (range, 0-4.75) years. RESULTS: Thirty-one patients with OLL
      were referred for patch testing. Ten (32%) patients tested positively to mercury.
      Eight patients with positive reactions to mercury had amalgam removal, with
      complete or partial resolution of the OLL in all cases (100%). CONCLUSIONS:
      Patients with OLL of unclear etiology adjacent to large amalgam restorations
      should be investigated for delayed contact hypersensitivity. Removal of amalgams
      in patients with positive patch test reactions to mercury results in improvement
      or resolution of the OLL in most patients.

PMID- 25757081
TI  - Patch testing custom isocyanate materials from the workplace.
AB  - BACKGROUND: Patch testing with standard trays of commercially available allergens
      is the current practice for investigating suspected cases of isocyanate-induced
      allergic contact dermatitis (ACD). In some facilities, these standard trays are
      further supplemented with custom preparations of isocyanate-containing materials.
      OBJECTIVE: The aim was to determine whether added value exists in patch testing
      patients to custom isocyanate preparations in suspected cases of ACD. METHODS: We
      performed a retrospective analysis of 11 patients referred to our specialty
      clinic between January 2003 and March 2011 for suspected patients of ACD who had
      custom testing with isocyanate materials from their workplace. In addition to
      standard trays of allergens, all patients were patch tested with custom
      isocyanate materials from their workplaces. RESULTS: Three (27%) of 11 patients
      showed an added value in testing to custom isocyanate allergens. Of these 3
      patients, one had a reaction that reinforced positive reactions to the standard
      isocyanate tray, but the other 2 (18%) had no reactions to any of the
      commercially available allergens. CONCLUSIONS: Because of the high proportion of
      reactions (27%), we recommend the use of custom testing to workplace isocyanate
      products as a supplement to current standard patch testing procedures.

PMID- 25757082
TI  - Methylchloroisothiazolinone/Methylisothiazolinone and methylisothiazolinone
      allergy.
AB  - BACKGROUND: Preservatives used in cosmetics tend to be, by their nature,
      allergenic. Methylisothiazolinone (MI) has been used as a sole preservative in
      multiple cosmetics, household goods, and toiletries. A current epidemic of MI has
      recently been reported in Europe. OBJECTIVE: The aim of this study was to study
      the prevalence of methylchloroisothiazolinone/MI (MCI/MI) and MI allergy in a
      Bangkok dermatology clinic. METHODS: During January 2009 to June 2014, 3253
      consecutive patients tested with 100 ppm (0.01%) MCI/MI and patients tested with
      2000 ppm (0.2%) MI were included in the study. RESULTS: Three hundred twenty of
      3253 patients (9.8%) tested for MCI/MI had a positive reaction. There was a steep
      increase in the prevalence of MCI/MI contact allergy from 4.8% in 2009 to 11.2%
      in 2011 and 17% in 2013. In the first 6 months of 2014, 22 of 54 cases tested for
      MI (40.7%) had a positive reaction. Among those who had a positive reaction to
      MI, 6 of 22 (27.3%) showed negative reaction to MCI/MI. CONCLUSIONS: There is a
      similar prevalence of MI allergy in a Bangkok dermatology clinic as those
      reported in European centers such in the United Kingdom.

PMID- 25757083
TI  - Occupational sensitization to acrylates with paresthesias.

PMID- 25757084
TI  - Fermented rice flour in pediatric atopic dermatitis.

PMID- 25757085
TI  - Modeling the interaction between quinolinate and the receptor for advanced
      glycation end products (RAGE): relevance for early neuropathological processes.
AB  - The receptor for advanced glycation end products (RAGE) is a pattern-recognition
      receptor involved in neurodegenerative and inflammatory disorders. RAGE induces
      cellular signaling upon binding to a variety of ligands. Evidence suggests that
      RAGE up-regulation is involved in quinolinate (QUIN)-induced toxicity. We
      investigated the QUIN-induced toxic events associated with early noxious
      responses, which might be linked to signaling cascades leading to cell death. The
      extent of early cellular damage caused by this receptor in the rat striatum was
      characterized by image processing methods. To document the direct interaction
      between QUIN and RAGE, we determined the binding constant (Kb) of RAGE (VC1
      domain) with QUIN through a fluorescence assay. We modeled possible binding sites
      of QUIN to the VC1 domain for both rat and human RAGE. QUIN was found to bind at
      multiple sites to the VC1 dimer, each leading to particular mechanistic scenarios
      for the signaling evoked by QUIN binding, some of which directly alter RAGE
      oligomerization. This work contributes to the understanding of the phenomenon of
      RAGE-QUIN recognition, leading to the modulation of RAGE function. 

PMID- 25757086
TI  - Are human peripheral nerves sensitive to X-ray imaging?
AB  - Diagnostic imaging techniques play an important role in assessing the exact
      location, cause, and extent of a nerve lesion, thus allowing clinicians to
      diagnose and manage more effectively a variety of pathological conditions, such
      as entrapment syndromes, traumatic injuries, and space-occupying lesions.
      Ultrasound and nuclear magnetic resonance imaging are becoming useful methods for
      this purpose, but they still lack spatial resolution. In this regard, recent
      phase contrast x-ray imaging experiments of peripheral nerve allowed the
      visualization of each nerve fiber surrounded by its myelin sheath as clearly as
      optical microscopy. In the present study, we attempted to produce high-resolution
      x-ray phase contrast images of a human sciatic nerve by using synchrotron
      radiation propagation-based imaging. The images showed high contrast and high
      spatial resolution, allowing clear identification of each fascicle structure and
      surrounding connective tissue. The outstanding result is the detection of such
      structures by phase contrast x-ray tomography of a thick human sciatic nerve
      section. This may further enable the identification of diverse pathological
      patterns, such as Wallerian degeneration, hypertrophic neuropathy, inflammatory
      infiltration, leprosy neuropathy and amyloid deposits. To the best of our
      knowledge, this is the first successful phase contrast x-ray imaging experiment
      of a human peripheral nerve sample. Our long-term goal is to develop peripheral
      nerve imaging methods that could supersede biopsy procedures. 

PMID- 25757088
TI  - Primary care of women who have sex with women. Recommendations from the research.
AB  - Research on women who have sex with women has increased in the last decade.
      Attention has been brought to this group of women through the IOM report, which
      noted a lack of research related to their care. Most of the research has not been
      published in nursing literature. This article reviews this literature with
      recommendations for primary care practice. 

PMID- 25757089
TI  - Effect of MPG gene rs2858056 polymorphism, copy number variation, and level of
      serum MPG protein on the risk for rheumatoid arthritis.
AB  - OBJECTIVE: This study examined the role of SNP rs2858056 of the MPG gene on the
      incidence and severity of rheumatoid arthritis (RA). METHODS: This cohort study
      enrolled 365 RA patients and 375 age- and gender-matched healthy controls, all of
      whom had Han Chinese ethnicity and were from Taiwan. Gene polymorphism of the SNP
      rs2858056 of MPG was determined from genomic DNA. Allelic frequencies and
      genotypes were compared among cases and controls. Quantitation of rs2858056 copy
      number variation (CNV) was determined. Serum samples from RA patients and
      controls were analyzed to determine serum levels of MPG. The relationship between
      rs2858056 polymorphism and clinical manifestations of RA was evaluated. RESULTS:
      Our results indicated a statistically significant difference in genotype
      frequency distributions at rs2858056 for RA patients and controls (p = 0.05) and
      a significant difference in allelic frequency in patients and controls (p =
      0.04). Furthermore, there was a significantly greater level of serum MPG protein
      in patients than controls (p < 0.001). However, the cases and controls had no
      significant differences in MPG CNV (p = 0.12). We also did not detect any
      association of the MPG rs2858056 with rheumatoid factor (RF), extraarticular
      involvement, or bone erosion in the RA patients. CONCLUSION: Our study suggests
      that RA is associated with a polymorphism in the MPG gene (rs2858056) and
      increased serum level of the MPG protein.

PMID- 25757087
TI  - CXCR2 modulates bone marrow vascular repair and haematopoietic recovery post
      transplant.
AB  - Murine models of bone marrow transplantation show that pre-conditioning regimens
      affect the integrity of the bone marrow endothelium and that the repair of this
      vascular niche is an essential pre-requisite for successful haematopoietic stem
      and progenitor cell engraftment. Little is known about the angiogenic pathways
      that play a role in the repair of the human bone marrow vascular niche. We
      therefore established an in vitro humanized model, composed of bone marrow
      stromal and endothelial cells and have identified several pro-angiogenic factors,
      VEGFA, ANGPT1, CXCL8 and CXCL16, produced by the stromal component of this niche.
      We demonstrate for the first time that addition of CXCL8 or inhibition of its
      receptor, CXCR2, modulates blood vessel formation in our bone marrow endothelial
      niche model. Compared to wild type, Cxcr2(-/-) mice displayed a reduction in bone
      marrow cellularity and delayed platelet and leucocyte recovery following
      myeloablation and bone marrow transplantation. The delay in bone marrow recovery
      correlated with impaired bone marrow vascular repair. Taken together, our data
      demonstrate that CXCR2 regulates bone marrow blood vessel repair/regeneration and
      haematopoietic recovery, and clinically may be a therapeutic target for improving
      bone marrow transplantation. 

PMID- 25757090
TI  - Historical changes in the ecosystem condition of a small mountain lake over the
      past 60 years as revealed by plankton remains and Daphnia ephippial carapaces
      stored in lake sediments.
AB  - To examine if changes in species composition of a plankton community in the past
      due to anthropogenic activities can be clarified in lakes without any monitoring
      data, we analyzed genetically ephippial carapaces of Daphnia with plankton
      remains stored in the bottom sediments of Lake Hataya Ohunma in Japan. In the
      lake, abundance of most plankton remains in the sediments was limited and TP flux
      was at low levels (2-4 mg/m2/y) before 1970. However TP flux increased two-fold
      during the period from 1980s to 1990 s. In parallel with this increase, abundance
      of most plankton remains increased although abundance of benthic testate
      amoebae's remains decreased, indicating that the lake trophic condition had
      changed from oligo- to mesotrophic for the past 60 years. According to cluster
      analysis, the stratigraphic sediments were divided into two periods with
      different features of the phytoplankton composition. Chronological comparison
      with events in the watershed suggested that eutrophication occurred because of an
      increase in visitors to the watershed and deposition of atmospheric dust. In this
      lake more than 50% of resting eggs produced by Daphnia over the past 60 years
      hatched. However, genetic analysis of the ephippial carapaces (remains) showed
      that the Daphnia population was originally composed of D. dentifera but that D.
      galeata, or its hybrid with D. dentifera, invaded and increased the population
      density when the lake was eutrophied. Subsequently, large D. pulex established
      populations in the 1980s when largemouth bass were anonymously introduced. These
      results indicated that the Lake Hataya Ohunma plankton community underwent
      significant changes despite the fact that there were no notable changes in land
      cover or land use in the watershed. Since increases in atmospheric deposition and
      release of fish have occurred in many Japanese lakes, the changes in the plankton
      community described here may be widespread in these lakes.

PMID- 25757091
TI  - Association of GDF5, SMAD3 and RUNX2 polymorphisms with temporomandibular joint
      osteoarthritis in female Han Chinese.
AB  - Temporomandibular joint osteoarthritis (TMJOA) is a complex disease and has a
      strong genetic component in its pathogenesis. Experimental evidence suggests the
      involvement of biological pathway in the disease. This case-control study was
      designed to investigate whether five common single nucleotide polymorphisms
      (SNPs) in GDF5, SMAD3, RUNX2, TGFbeta1 and CHST11, respectively, are associated
      with TMJOA in female Han Chinese patients. A total of 240 participants were
      evaluated comprising 114 female patients diagnosed with TMJOA based on Research
      Diagnostic Criteria for Temporomandibular Disorders and 126 healthy female
      controls. The SNPs of the five genes in the genomic DNA were examined by
      sequencing, and their allelic, genotypic and carriage rate frequency
      distributions, as well as the triple combination of the risk genotypes, were
      analysed using the logistic regression model. The SNP in GDF5 or SMAD3 showed
      significant association with TMJOA, a relatively weak association was observed in
      RUNX2. In the triple combinational analysis, the risk of TMJOA grew 5.09 times in
      the patients with five or six risk alleles (P < 0.01). This is the first study to
      evaluate the association of GDF5, SMAD3, RUNX2, TGFbeta1 and CHST11 with TMJOA in
      female Han Chinese. Our study suggests that the SNPs of genes related to TGFbeta
      family might contribute to the risk of TMJOA. 

PMID- 25757092
TI  - Luotonin-A based quinazolinones cause apoptosis and senescence via HDAC
      inhibition and activation of tumor suppressor proteins in HeLa cells.
AB  - A series of novel quinazolinone hybrids were synthesized by employing click
      chemistry and evaluated for anti-proliferative activities against MCF-7, HeLa and
      K562 cell lines. Among these cell lines, HeLa cells were found to respond
      effectively to these quinazolinone hybrids with IC50 values ranging from 5.94 to
      16.45 MUM. Some of the hybrids (4q, 4r, 4e, 4k, 4t, 4w) with promising anti
      cancer activity were further investigated for their effects on the cell cycle
      distribution. FACS analysis revealed the G1 cell cycle arrest nature of these
      hybrids. Further to assess the senescence inducing ability of these compounds, a
      senescence associated beta-gal assay was performed. The senescence inducing
      nature of these compounds was supported by the effect of hybrid (4q) on p16
      promoter activity, the marker for senescence. Moreover, cells treated with most
      effective compound (4q) show up-regulation of p53, p21 and down-regulation of
      HDAC-1, HDAC-2, HDAC-5 and EZH2 mRNA levels. Docking results suggest that, the
      triazole nitrogen showed Zn(+2) mediated interactions with the histidine residue
      of HDACs.

PMID- 25757093
TI  - Synthesis and biological evaluation of novel 2-heteroarylimino-1,3-thiazolidin-4
      ones as potential anti-tumor agents.
AB  - A series of 35 heteroarylimino-1,3-thiazolidinones with three sites of
      functionalization were synthesized and their antiproliferative properties were
      studied. The in vitro screening by MTT assay was performed against five cancer
      cell lines (human colon cancer cell lines HT29, HCT116 and SW620 and breast
      cancer cell lines MCF7 and MDA-MB-231). It was observed that N3-substituted
      thiazolidinones had moderate activities whereas 5-benzylidene thiazolidinones
      showed promising activities. To investigate the mechanism of action, detailed
      biological studies of six selected compounds (those presenting the lower mitotic
      index) were carried out on the human colon cancer HT29 cell line. Cell cycle
      assay revealed that those compounds induced cell accumulation in G2/M and in
      subG0/G1 phases of cell cycle. Moreover, dissipation of mitochondria membrane
      potential was observed as well as redox changes in treated cells. 

PMID- 25757094
TI  - New platelet aggregation inhibitors based on pyridazinone moiety.
AB  - New series of pyridazinone derivatives (4, 5 and 6) were synthesized in good
      yields following a synthetic strategy based on singlet oxygen oxidation of alkyl
      furans, in which a suitable beta(alpha)-substituted gamma-hydroxybutenolide (10
      or 11) or a bicyclic lactone (12 or 13) was the key intermediate. The synthesized
      compounds were tested in vitro as antiplatelet agents and some of them (compounds
      4b, 4d and 5b) exhibited potent inhibitory effects on collagen-induced platelet
      aggregation with IC50 values in the low MUM range. Studies performed with the
      most active compound of these series (4b) demonstrated its lack of activity as
      inhibitor of platelet aggregation induced by other agonists as thrombin,
      ionomycin or U-46619 suggesting a selective action on the biochemical mechanisms
      triggered by collagen in the platelets.

PMID- 25757095
TI  - The juvenile head trauma syndrome: a trauma triggered migraine?
AB  - BACKGROUND: The underlying mechanism of the juvenile head trauma syndrome (JHTS)
      is still uncertain, but it has been suggested that there is a role in cortical
      spreading depression, a phenomenon that is assumed to be a part of the
      pathophysiology of migraine. HYPOTHESIS: We postulate that children affected by
      the JHTS are more susceptible to cortical spreading depression, caused by a
      genetic etiology similar to genetic factors in migraine. METHODS: Children with
      the JHTS were selected and evaluated retrospectively in an observational case
      control study in two Dutch trauma centers in the period between January 2008 and
      July 2012. RESULTS: We included 33 patients with the JHTS, who were accounted for
      approximately 2.5% of the total number (1,342) of children seen at the emergency
      department with a mild head trauma. The prevalence of migraine in cases compared
      with controls did not differ. The proportion of patients with a first-degree
      relative with migraine was significantly higher in cases compared with controls
      (odds ratio, 2.69; 95% confidence interval, 1.16-6.22; p = 0.010). CONCLUSION:
      The JHTS is a relatively rare phenomenon, seen in approximately 2.5% of all
      children seen at the emergency department with mild brain injury. This study
      demonstrates a significant relationship between the JHTS and a positive history
      of migraine in first-degree relatives.

PMID- 25757096
TI  - Hereditary orotic aciduria with epilepsy and without megaloblastic anemia.
AB  - Hereditary orotic aciduria is a rare metabolic disease that results from a defect
      of uridine-5-monophosphate synthase (UMPS). In affected patients, main clinical
      symptoms are a markedly increased urinary excretion of orotic acid combined with
      megaloblastic anemia. This report describes a new case of UMPS deficiency without
      megaloblastic anemia but with epilepsy. 

PMID- 25757097
TI  - Exploring ComQXPA quorum-sensing diversity and biocontrol potential of Bacillus
      spp. isolates from tomato rhizoplane.
AB  - Bacillus subtilis is a widespread and diverse bacterium t exhibits a remarkable
      intraspecific diversity of the ComQXPA quorum-sensing (QS) system. This manifests
      in the existence of distinct communication groups (pherotypes) that can
      efficiently communicate within a group, but not between groups. Similar QS
      diversity was also found in other bacterial species, and its ecological and
      evolutionary meaning is still being explored. Here we further address the ComQXPA
      QS diversity among isolates from the tomato rhizoplane, a natural habitat of B.
      subtilis, where these bacteria likely exist in their vegetative form. Because
      this QS system regulates production of anti-pathogenic and biofilm-inducing
      substances such as surfactins, knowledge on cell-cell communication of this
      bacterium within rhizoplane is also important from the biocontrol perspective. We
      confirm the presence of pherotype diversity within B. subtilis strains isolated
      from a rhizoplane of a single plant. We also show that B. subtilis rhizoplane
      isolates show a remarkable diversity of surfactin production and potential plant
      growth promoting traits. Finally, we discover that effects of surfactin deletion
      on biofilm formation can be strain specific and unexpected in the light of
      current knowledge on its role it this process. 

PMID- 25757099
TI  - Frustrated Lewis pair-like reactions of nucleophilic palladium carbenes with
      B(C6F5)3.
AB  - The reactions of two nucleophilic palladium carbene complexes with the strong
      Lewis acid B(C6F5)3 afforded two zwitterionic products. One of them features a
      remote nucleophilic attack at the para-carbon of the supporting ligand, while the
      other indicates C-F activation of B(C6F5)3. Both behaviours are reminiscent of
      the reactivity of frustrated Lewis pairs due to the steric inaccessibility of the
      nucleophilic carbon center, but are unprecedented for transition metal carbene
      complexes. Furthermore, when those reactions are carried out in the presence of
      H2, products resulting from H2 splitting are observed. 

PMID- 25757098
TI  - Local adaptation in migrated interior Douglas-fir seedlings is mediated by
      ectomycorrhizas and other soil factors.
AB  - Separating edaphic impacts on tree distributions from those of climate and
      geography is notoriously difficult. Aboveground and belowground factors play
      important roles, and determining their relative contribution to tree success will
      greatly assist in refining predictive models and forestry strategies in a
      changing climate. In a common glasshouse, seedlings of interior Douglas-fir
      (Pseudotsuga menziesii var. glauca) from multiple populations were grown in
      multiple forest soils. Fungicide was applied to half of the seedlings to separate
      soil fungal and nonfungal impacts on seedling performance. Soils of varying
      geographic and climatic distance from seed origin were compared, using a transfer
      function approach. Seedling height and biomass were optimized following seed
      transfer into drier soils, whereas survival was optimized when elevation transfer
      was minimised. Fungicide application reduced ectomycorrhizal root colonization by
      c. 50%, with treated seedlings exhibiting greater survival but reduced biomass.
      Local adaptation of Douglas-fir populations to soils was mediated by soil fungi
      to some extent in 56% of soil origin by response variable combinations. Mediation
      by edaphic factors in general occurred in 81% of combinations. Soil biota,
      hitherto unaccounted for in climate models, interacts with biogeography to
      influence plant ranges in a changing climate. 

PMID- 25757100
TI  - Enhanced mobility and effective control of threshold voltage in P3HT-based field
      effect transistors via inclusion of oligothiophenes.
AB  - Improved organic field-effect transistor (OFET) performance through a polymer
      oligomer semiconductor blend approach is demonstrated. Incorporation of 2,5-bis(3
      dodecylthiophen-2-yl)thieno[3,2-b]thiophene (BTTT) into poly(3-hexylthiophene)
      (P3HT) thin films leads to approximately a 5-fold increase in charge carrier
      mobility, a 10-fold increase in current on-off ratio, and concomitantly, a
      decreased threshold voltage to as low as 1.7 V in comparison to single component
      thin films. The blend approach required no pre- and/or post treatments, and
      processing was conducted under ambient conditions. The correlation of
      crystallinity, surface morphology and photophysical properties of the blend thin
      films was systematically investigated via X-ray diffraction, atomic force
      microscopy and optical absorption measurements respectively, as a function of
      blend composition. The dependence of thin-film morphology on the blend
      composition is illustrated for the P3HT:BTTT system. The blend approach provides
      an alternative avenue to combine the advantageous properties of conjugated
      polymers and oligomers for optimized semiconductor performance. 

PMID- 25757101
TI  - Novel and Selective Fluorescent sigma2 -Receptor Ligand with a 3,4
      Dihydroisoquinolin-1-one Scaffold: A Tool to Study sigma2 Receptors in Living
      Cells.
AB  - Although sigma-2 (sigma2 ) receptors are still enigmatic proteins, they are
      promising targets for tumor treatment and diagnosis. With the aim of clarifying
      their role in oncology, we developed a sigma2 -selective fluorescent tracer
      (compound 5) as a specific tool to study sigma2 receptors. By using flow
      cytometry with 5, we performed competition binding studies on three different
      cell lines where we also detected the content of the sigma2 receptors, avoiding
      the inconvenient use of radioligands. Comparison with a previously developed
      mixed sigma1 /sigma2 fluorescent tracer (1) also allowed for the detection of
      sigma1 receptors within these cells. Results obtained by flow cytometry with
      tracers 1 and 5 were confirmed by standard methods (western blot for sigma1 , and
      Scatchard analysis for sigma2 receptors). Thus, we have produced powerful new
      tools for research on the sigma whose reliability and adaptability to a number of
      fluorescence techniques will be useful to elucidate the roles of sigma receptors
      in oncology. 

PMID- 25757103
TI  - Copper-incorporated mono- and di-TeRu5 metal carbonyl complexes: syntheses,
      structures, and an unusual skeletal arrangement.
AB  - Two sandwich-type Cu3Cl- or Cu2{Te2Ru4(CO)10}-bridging di-TeRu5 clusters,
      [{TeRu5(CO)14}2Cu3Cl](2-) () and [{TeRu5(CO)14}2Cu2{Te2Ru4(CO)10}](4-) (), were
      obtained from the reaction of [TeRu5(CO)14](2-) with 1 equiv. of [Cu(MeCN)4][BF4]
      in CH2Cl2 or THF at 0  degrees C, respectively, depending on the solvents. The
      chloride-abstracted was structurally characterized to have two TeRu5 cores that
      were linked by a Cu3Cl moiety with two Cu-Cu bonds. If the reaction was carried
      out in a molar ratio of 1 : 2 at 0 or 30  degrees C in CH2Cl2, the structural
      isomers [TeRu5(MU-CO)2(CO)12(CuMeCN)2] () and [TeRu5(MU-CO)3(CO)11Cu2(MeCN)2] ()
      were produced, respectively, as the major product. Cluster displayed a TeRu5 core
      with two adjacent Ru3 triangles each capped by a MU3-Cu(MeCN) fragment, while
      contained a TeRu5 core with one triangle Ru3 plane capped by a Cu2(MeCN)2
      fragment with two Cu atoms covalently bonded. Upon heating, the isomerization of
      into proceeded to undergo an unusual skeletal arrangement of Cu(MeCN) and
      migration of CO, with the TeRu5 core remaining intact. An electrochemical study
      revealed that and each exhibited only one oxidation while cluster had two
      consecutive oxidations, suggesting significant electronic communication between
      the two TeRu5 metal cores in via the Cu3 moiety. This work describes the facile
      synthesis of a series of semiconducting Cux-bridging Te-Ru carbonyl clusters, in
      which the incorporation of the Cux fragments has significantly influenced their
      resulting structures, rearrangements, and electronic properties, which was
      further elucidated by DFT calculations. 

PMID- 25757102
TI  - Maternal co-ordinate gene regulation and axis polarity in the scuttle fly
      Megaselia abdita.
AB  - Axis specification and segment determination in dipteran insects are an excellent
      model system for comparative analyses of gene network evolution. Antero-posterior
      polarity of the embryo is established through systems of maternal morphogen
      gradients. In Drosophila melanogaster, the anterior system acts through opposing
      gradients of Bicoid (Bcd) and Caudal (Cad), while the posterior system involves
      Nanos (Nos) and Hunchback (Hb) protein. These systems act redundantly. Both Bcd
      and Hb need to be eliminated to cause a complete loss of polarity resulting in
      mirror-duplicated abdomens, so-called bicaudal phenotypes. In contrast, knock
      down of bcd alone is sufficient to induce double abdomens in non-drosophilid
      cyclorrhaphan dipterans such as the hoverfly Episyrphus balteatus or the scuttle
      fly Megaselia abdita. We investigate conserved and divergent aspects of axis
      specification in the cyclorrhaphan lineage through a detailed study of the
      establishment and regulatory effect of maternal gradients in M. abdita. Our
      results show that the function of the anterior maternal system is highly
      conserved in this species, despite the loss of maternal cad expression. In
      contrast, hb does not activate gap genes in this species. The absence of this
      activatory role provides a precise genetic explanation for the loss of polarity
      upon bcd knock-down in M. abdita, and suggests a general scenario in which the
      posterior maternal system is increasingly replaced by the anterior one during the
      evolution of the cyclorrhaphan dipteran lineage. 

PMID- 25757104
TI  - The American Association for the Surgery of Trauma PROspective Observational
      Vascular Injury Treatment (PROOVIT) registry: multicenter data on modern vascular
      injury diagnosis, management, and outcomes.
AB  - BACKGROUND: There is a need for a prospective registry designed to capture trauma
      specific, in-hospital, and long-term outcomes related to vascular injury.
      METHODS: The American Association for the Surgery of Trauma PROspective Vascular
      Injury Treatment (PROOVIT) registry was used to collect demographic, diagnostic,
      treatment, and outcome data on vascular injuries. RESULTS: A total of 542
      injuries from 14 centers (13 American College of Surgeons-verified Level I and 1
      American College of Surgeons-verified Level II) have been captured since February
      2013. The majority of patients are male (70.5%), with an Injury Severity Score
      (ISS) of 15 or greater among 32.1%. Penetrating mechanisms account for 36.5%.
      Arterial injuries to the head/neck (26.7%), thorax (10.4%), abdomen/pelvis
      (7.8%), upper extremity (18.4%), and lower extremity (26.0%) were identified,
      along with 98 major venous injuries. Hard signs of vascular injury, including
      hypotension (systolic blood pressure < 90 mm Hg, 11.8%), were noted in 28.6%.
      Prehospital tourniquet use for extremity injuries occurred in 20.2% (47 of 233).
      Diagnostic modalities included exploration (28.8%), computed tomographic
      angiography (38.9%), duplex ultrasound (3.1%), and angiography (10.7%). Arterial
      injuries included transection (24.3%), occlusion (17.3%), partial
      transection/flow limiting defect (24.5%), pseudoaneurysm (9.0%), and other
      injuries including intimal defects (22.7%). Nonoperative management was
      undertaken in 276 (50.9%), with failure in 4.0%. Definitive endovascular and open
      repair were used in 40 (7.4%) and 126 (23.2%) patients, respectively. Damage
      control maneuvers were used in 57 (10.5%), including ligation (31, 5.7%) and
      shunting (14, 2.6%). Reintervention of initial repair was required in 42 (7.7%).
      Amputation was performed in 7.7% of extremity vascular injuries, and overall
      hospital mortality was 12.7%. Follow-up ranging from 1 month to 7 months is
      available for 48 patients via a variety of modalities, with reintervention
      required in 1 patient. CONCLUSION: The PROOVIT registry provides a contemporary
      picture of the management of vascular injury. This resource promises to provide
      needed information required to answer questions about optimal diagnosis and
      management of these patients-including much needed long-term outcome data. LEVEL
      OF EVIDENCE: Epidemiologic study, level V.

PMID- 25757105
TI  - The new metric to define large-volume hemorrhage: results of a prospective study
      of the critical administration threshold.
AB  - BACKGROUND: Definitions of massive transfusion (MT), 10 or more units of packed
      red blood cells (PRBCs) in 24 hours, focus on static volumes over fixed times.
      This arbitrary volume definition promotes survivor bias and fails to identify the
      "massively" transfused patient. In previous work, the critical administration
      threshold (CAT) was created to incorporate both rate and volume of transfusion.
      CAT proved a superior predictor of mortality compared with traditional MT. The
      purpose of this study was to prospectively validate CAT in a larger trauma
      population. METHODS: Patients receiving at least 1 U of PRBCs within the first
      day of admission were identified prospectively. Administration time of each unit
      of PRBCs was recorded in minutes. CAT status, defined as receipt of at least 3 U
      of blood in a 60-minute period, was identified for the first 24 hours. CAT+
      patients were quantified by the number of times CAT+ was reached, that is, once
      (CAT1), twice (CAT2), three times (CAT3), or 4 or more times (CAT4). A
      multivariable Cox proportional hazard model with a time-varying covariate was
      used to quantify a patient's risk of death with increasing CAT status. RESULTS: A
      total of 316 met inclusion criteria, 161 of whom were CAT+. Seventy-six percent
      were male, mean age was 38 years, and median Injury Severity Score (ISS) was 15.
      CAT+ was associated with a twofold increased risk of death (hazard ratio, 1.809;
      95% confidence interval, 1.020-3.209). Ninety-one patients were CAT+ and received
      less than 10 U of blood, thereby MT- (CAT+/MT-). CAT+/MT- had significant injury
      patterns, with a median ISS of 14, 43% penetrating injury, and 10% mortality.
      CONCLUSION: CAT allows early identification of injured patients at greatest risk
      of death. Encompassing both rate and volume of transfusion, CAT is a tool more
      sensitive than common MT definitions. Studies examining large-volume blood
      transfusions should use CAT to identify patients, to accurately identify cohorts
      of interest. LEVEL OF EVIDENCE: Diagnostic tests, level II.

PMID- 25757106
TI  - Reconstitution fluid type does not affect pulmonary inflammation or DNA damage
      following infusion of lyophilized plasma.
AB  - BACKGROUND: Dysfunctional inflammation following traumatic hemorrhage can lead to
      multiple-organ failure and death. In our polytrauma swine model, lyophilized
      plasma (LP) reconstituted with sterile water and ascorbic acid suppressed
      systemic inflammation and attenuated DNA damage. However, it remains unknown
      whether the inflammatory response is affected by the type of fluid used to
      reconstitute LP. We hypothesized that common resuscitation fluids such as normal
      saline (LP-NS), lactated Ringer's solution (LP-LR), Hextend (LP-HX), or sterile
      water (LP-SW) would yield similar inflammation profiles and DNA damage following
      LP reconstitution and transfusion. METHODS: This was a randomized, prospective,
      blinded animal study. LP was reconstituted to 50% of original volume with NS, LR,
      HX, or SW buffered with 15-mM ascorbic acid. Forty swine were subjected to a
      validated model of polytrauma, hemorrhagic shock, and Grade V liver injury and
      resuscitated with LP. Serum interleukin 6 (IL-6), IL-10, plasma C-reactive
      protein, and 8-hydroxy-2-deoxyguanosine concentrations were assessed for systemic
      inflammation and DNA damage at baseline, 2 hours, and 4 hours following liver
      injury. Lung inflammation was evaluated by Real Time Polymerize Chain Reaction
      (RT-PCR). RESULTS: Reconstituted LP pH was similar between groups before
      resuscitation. IL-6 and IL-10 increased at 2 hours and 4 hours compared with
      baseline in all groups (p < 0.017). DNA damage increased at 2 hours and 4 hours
      compared with baseline and from 2 hours to 4 hours in the LP-NS, LP-LR, and LP-SW
      groups (all p < 0.017). Animals resuscitated with LP-HX not only demonstrated
      increased DNA damage at 4 hours versus baseline but also had the lowest C
      reactive protein level at 2 hours and 4-hours (p < 0.017). Overall, differences
      between groups were similar for DNA damage and lung inflammation. CONCLUSION:
      Reconstitution fluid type does not affect inflammatory cytokine profiles or DNA
      damage following LP transfusion in this swine polytrauma model. Based on
      universal availability, these data suggest that sterile water is the most logical
      choice for LP reconstitution in humans. LEVEL OF EVIDENCE: Prognostic, level II.

PMID- 25757108
TI  - Saving lives and saving money: hospital-based violence intervention is cost
      effective.
AB  - BACKGROUND: Victims of violence are at significant risk for injury recidivism,
      including fatality. We previously demonstrated that our hospital-based violence
      intervention program (VIP) resulted in a fourfold reduction in injury recidivism,
      avoiding trauma care costs of $41,000 per injury. Given limited trauma center
      resources, assessing cost-effectiveness of interventions is fundamental to inform
      use of these programs in other institutions. This study examines the cost
      effectiveness of hospital-based VIP. METHODS: We used a decision tree and Markov
      disease state modeling to analyze cost utility for a hypothetical cohort of
      violently injured subjects, comparing VIP versus no VIP at a trauma center.
      Quality-adjusted life-years (QALYs) were calculated using differences in
      mortality and published health state utilities. Costs of trauma care and VIP were
      obtained from institutional data, and risk of recidivism with and without VIP
      were obtained from our trial. Outcomes were QALYs gained and net costs over a 5
      year horizon. Sensitivity analyses examined the impact of uncertainty in input
      values on results. RESULTS: VIP results in an estimated 25.58 QALYs and net costs
      (program plus trauma care) of $5,892 per patient. Without VIP, these values are
      25.34 and $5,923, respectively, suggesting that VIP yields substantial health
      benefits (24 QALYs) and savings ($4,100) if implemented for 100 individuals. In
      the sensitivity analysis, net QALYs gained with VIP nearly triple when the injury
      recidivism rate without VIP is highest. Cost-effectiveness remained robust over a
      range of values; $6,000 net cost savings occur when 5-year recidivism rate
      without VIP is at 7%. CONCLUSION: VIP costs less than having no VIP with
      significant gains in QALYs especially at anticipated program scale. Across a
      range of plausible values at which VIP would be less cost-effective (lower injury
      recidivism, cost of injury, and program effectiveness), VIP still results in
      acceptable cost per health outcome gained. VIP is effective and cost-effective
      and should be considered in any trauma center that takes care of violently
      injured patients. Our analyses can be used to estimate VIP costs and results in
      different settings. LEVEL OF EVIDENCE: Economic and value-based evaluation, level
      2.

PMID- 25757109
TI  - Defining the acute care surgery curriculum.
AB  - BACKGROUND: This study was designed to define the gaps in essential and desirable
      (E/D) case volumes that may prompt reevaluation of the acute care surgery (ACS)
      curriculum or restructuring of the training provided. METHODS: A review of the
      first 2 years of ACS case log entry (July 2011 to June 2013) was performed.
      Individual trainee logs were evaluated to determine how often they performed each
      case on the E/D list. Trainees described cases using current procedural
      terminology codes, which had been previously mapped to the E/D list. RESULTS:
      There were 29 trainees from 15 programs (Year 1) and 30 trainees from 13 programs
      (Year 2) who participated in case log entry, with some overlap between the years.
      There were a total of 487 fellow-months of data with an average of 14.6 current
      procedural terminology codes per month and 175.5 per year for cases on the E/D
      list versus 12 and 143.5 for cases not on the E/D list, respectively. Overall,
      the most common essential cases were laparotomy for trauma (1,463; 705 in Year 1,
      758 in Year 2), tracheostomy (665; 372 in Year 1, 293 in Year 2) and gastrostomy
      tubes (566; 289 in Year 1, 277 in Year 2). There are a total of 73 types of
      essential operations and 45 types of desirable operations in the current
      curriculum. There were 16 distinct codes (13.6%) never used, of which 6
      overlapped with other codes. Based on body region, the 10 E/D codes never used by
      any fellow were as follows: one head/face, lateral canthotomy; five neck;
      elective neck dissections; one thoracic, vascular trauma to chest; three
      pediatrics, inguinal hernia repair and small bowel obstruction treatments.
      CONCLUSION: The current ACS trainees lack adequate head/neck and pediatric
      experience as defined by the ACS curriculum. Restructuring rotations at
      individual institutions and a focus on novel educational modalities may be needed
      to augment the individual institutional exposure. Reevaluation of the curriculum
      may be warranted.

PMID- 25757107
TI  - Lung protective ventilation (ARDSNet) versus airway pressure release ventilation:
      ventilatory management in a combined model of acute lung and brain injury.
AB  - BACKGROUND: Concomitant lung/brain traumatic injury results in significant
      morbidity and mortality. Lung protective ventilation (Acute Respiratory Distress
      Syndrome Network [ARDSNet]) has become the standard for managing adult
      respiratory distress syndrome; however, the resulting permissive hypercapnea may
      compound traumatic brain injury. Airway pressure release ventilation (APRV)
      offers an alternative strategy for the management of this patient population.
      APRV was hypothesized to retard the progression of acute lung/brain injury to a
      degree greater than ARDSNet in a swine model. METHODS: Yorkshire swine were
      randomized to ARDSNet, APRV, or sham. Ventilatory settings and pulmonary
      parameters, vitals, blood gases, quantitative histopathology, and cerebral
      microdialysis were compared between groups using chi2, Fisher's exact, Student's
      t test, Wilcoxon rank-sum, and mixed-effects repeated-measures modeling. RESULTS:
      Twenty-two swine (17 male, 5 female), weighing a mean (SD) of 25 (6.0) kg, were
      randomized to APRV (n = 9), ARDSNet (n = 12), or sham (n = 1). PaO2/FIO2 ratio
      dropped significantly, while intracranial pressure increased significantly for
      all three groups immediately following lung and brain injury. Over time, peak
      inspiratory pressure, mean airway pressure, and PaO2/FIO2 ratio significantly
      increased, while total respiratory rate significantly decreased within the APRV
      group compared with the ARDSNet group. Histopathology did not show significant
      differences between groups in overall brain or lung tissue injury; however,
      cerebral microdialysis trends suggested increased ischemia within the APRV group
      compared with ARDSNet over time. CONCLUSION: Previous studies have not evaluated
      the effects of APRV in this population. While our macroscopic parameters and
      histopathology did not observe a significant difference between groups,
      microdialysis data suggest a trend toward increased cerebral ischemia associated
      with APRV over time. Additional and future studies should focus on extending the
      time interval for observation to further delineate differences between groups.

PMID- 25757110
TI  - The impact and sustainability of the graduated driver licensing program in
      preventing motor vehicle crashes in Massachusetts.
AB  - BACKGROUND: Graduated driving licensing (GDL) programs phase in driving
      privileges for teenagers. We aimed to evaluate the effect of the 2007 GDL law on
      the incidence of total motor vehicle crashes (tMVCs) and fatal motor vehicle
      crashes (fMVCs) among teenagers in Massachusetts. METHODS: The Fatality Analysis
      and Reporting System, the Missouri Census Data Center, and the Massachusetts
      Department of Transportation databases were all used to create and compare the
      incidence of tMVCs and fMVCs before (2002-2006) and after (2007-2011) the law
      enactment. The following three driver age groups were studied: 16 years to 17
      years (evaluating the law effect), 18 years to 20 years (evaluating the
      sustainability of the effect), and 25 years to 29 years (control group). As a
      sensitivity analysis, we compared the incidence rates per population and per
      licenses issued. RESULTS: tMVCs decreased following the law for all three age
      groups (16-17 years, from 7.6 to 4.8 per 1,000 people, p < 0.0001; 18-20 years,
      from 8.5 to 6.4 per 1,000 people, p < 0.0001; 25-29 years, from 6.2 to 5.2 per
      1,000 people, p < 0.0001), but the percentage decrease in tMVC rates was less in
      the control group (37%, 25%, and 15%, respectively; both p's < 0.0001). The rates
      of fMVC also decreased in the age groups of 16 years to 17 years (from 14.0 to
      8.6 per 100,000 people, p = 0.0006), 18 years to 20 years (from 21.2 to 13.7 per
      100,000 people, p < 0.0001), and 25 years to 29 years (from 14.4 to 11.0 per
      100,000 people, p < 0.0001). All of these results were confirmed in the
      sensitivity analyses. CONCLUSION: The 2007 Massachusetts GDL was associated with
      a decreased incidence of teenager tMVCs and fMVCs, and the effect was
      sustainable. This study provides further support to develop, implement, enforce,
      and maintain GDL programs aimed at preventing MVCs and their related mortality in
      the young novice driver population. LEVEL OF EVIDENCE: Epidemiologic/prognostic
      study, level III.

PMID- 25757111
TI  - Mitochondrial damage-associated molecular patterns from fractures suppress
      pulmonary immune responses via formyl peptide receptors 1 and 2.
AB  - BACKGROUND: No known biologic mechanisms link tissue injury with pneumonia (PNA).
      Neutrophils (PMNs) are innate immune cells that clear bacteria from the lung by
      migration toward chemoattractants and killing bacteria in neutrophil
      extracellular traps (NETs). We predicted that tissue injury would suppress PMN
      antimicrobial function in the lung. We have also shown that mitochondria-derived
      damage-associated molecular pattern molecules from the bone can alter PMN
      phenotype and so hypothesized that formyl peptides (FPs) from fractures
      predispose to PNA by suppressing PMN activity in the lung. METHODS: Animal
      studies involved the following. (1) Rats were divided into three groups (10 per
      condition) as follows: (a) saline injection in the thigh (b) Staphylococcus
      aureus (SA, 3 * 10) injected intratracheally, or (c) pseudofracture (PsFx; bone
      supernatant injected in the thigh) plus intratracheally injected SA. (2) Rats
      were divided into four groups as follows: (a) control, (b) pulmonary contusion
      (PC), (c) PsFx, and (d) PC + PsFx. Bronchoalveolar lavage was performed 16 hours
      later. Clinical studies involved the following. (3) Human bone supernatant was
      assayed for its FP-receptor (FPR) stimulation. (4) Trauma patients' PMN (n = 32;
      mean +/- SE Injury Severity Score [ISS], 27 +/- 10) were assayed for chemotaxis
      (CTX) or treated with Phorbol 12-myristate 13-acetate (PMA, Phorbol ester) and
      analyzed for NET formation. RESULTS: In the animal studies, (1) SA was rapidly
      cleared by the uninjured mice and PsFx markedly suppressed lung bacterial
      clearance (p < 0.01). (2a) PC induces PMN traffic to the lung, but PsFx decreases
      PC-induced PMN traffic (p < 0.01). (2b) SA increased bronchoalveolar lavage PMN,
      and PsFx decreased that influx (p < 0.01). In the clinical studies, (3) bone
      supernatant activates PMN both via FPR-1 and FPR-2. (4) Trauma decreases PMN CTX
      to multiple chemokines. Circulating PMNs show NETs spontaneously after trauma,
      but maximal NET formation is markedly attenuated. CONCLUSION: Fractures may
      decrease lung bacterial clearance because FP suppresses PMN CTX to other
      chemoattractants via FPR-1/2. Trauma activates NETosis but suppresses maximal
      NETosis. Fractures decrease lung bacterial clearance by multiple mechanisms. PNA
      after fractures may reflect damage-associated molecular pattern-mediated
      suppression of PMN antimicrobial function in the lung.

PMID- 25757112
TI  - Outcomes following prolonged mechanical ventilation: analysis of a countywide
      trauma registry.
AB  - BACKGROUND: The care of mechanically ventilated patients at high-volume centers
      in select nontrauma populations has variable effects on outcomes. We evaluated
      outcomes for trauma patients requiring prolonged mechanical ventilation (PMV). We
      further hypothesized that the higher mechanical ventilator volume trauma center
      would have better outcomes. METHODS: A retrospective review of a county's trauma
      registry was performed for trauma patients who were at least 18 years old
      admitted from 2006 to 2010. Eleven hospitals serve this suburban county, with a
      population of approximately 1.5 million people. The state has designated them as
      nontrauma centers (n = 6), area trauma centers (ATCs, n = 4), or regional trauma
      center (RTC, n = 1), where the last one provides the highest echelon of care.
      Patients requiring mechanical ventilation for at least 96 hours following injury
      were evaluated. RESULTS: A total of 3,382 trauma patients were admitted to the
      RTC, and 5,870 were admitted to the other 10 hospitals in the county. Seven
      hundred seventy-one received mechanical ventilation at the RTC, and 687 at the
      other 10 hospitals combined. Of these patients, 407 at the RTC and 308 at the
      remaining facilities (291 at ATCs and 17 at nontrauma centers) required PMV.
      Median (interquartile range [IQR]) Injury Severity Score (ISS) at the RTC was
      higher (29 [21-41] vs. 22 [16-29] p < 0.001) than that at ATCs. Hospital length
      of stay (in days) was comparable between the RTC and ATCs (28 [18-45] vs. 26 [16
      44.7]). With regard to complications, rates of renal failure, sepsis, and
      myocardial infarction were similar. The RTC had higher pneumonia rates (59% vs.
      45.4%, p < 0.001) and venous thromboembolic disease rates (20.4% vs. 10.4%, p <
      0.001) than did ATCs. In-hospital mortality was 17% at the RTC and 34.4% at ATCs
      (p < 0.001). CONCLUSION: A mortality benefit but higher VTE and pneumonia rate
      for PMV patients at the RTC was noted. Collaborative practice initiatives are
      warranted to reduce morbidity and mortality across the region. LEVEL OF EVIDENCE:
      Epidemiologic study, level IV.

PMID- 25757113
TI  - Intraosseous infusion rates under high pressure: a cadaveric comparison of
      anatomic sites.
AB  - BACKGROUND: When traditional vascular access methods fail, emergency access
      through the intraosseous (IO) route can be lifesaving. Fluids, medications, and
      blood components have all been delivered through these devices. We sought to
      compare the performance of IO devices placed in the sternum, humeral head, and
      proximal tibia using a fresh human cadaver model. METHODS: Commercially available
      IO infusion devices were placed into fresh human cadavers: sternum (FAST-1),
      humeral head (EZ-IO), and proximal tibia (EZ-IO). Sequentially, the volume of
      0.9% saline infused into each site under 300 mm Hg pressure over 5 minutes was
      measured. Rates of successful initial IO device placement and subjective
      observations related to the devices were also recorded. RESULTS: For 16 cadavers
      over a 5-minute bolus infusion, the total volume of fluid infused at the three IO
      access sites was 469 (190) mL for the sternum, 286 (218) mL for the humerus, and
      154 (94) mL for the tibia. Thus, the mean (SD) flow rate infused at each site was
      as follows: (1) sternum, 93.7 (37.9) mL/min; (2) humerus, 57.1 (43.5) mL/min; and
      (3) tibia, 30.7 (18.7) mL/min. The tibial site had the greatest number of
      insertion difficulties. CONCLUSION: This is the first study comparing the rate of
      flow at the three most clinically used adult IO infusion sites in an adult human
      cadaver model. Our results showed that the sternal site for IO access provided
      the most consistent and highest flow rate compared with the humeral and tibial
      insertion sites. The average flow rate in the sternum was 1.6 times greater than
      in the humerus and 3.1 times greater than in the tibia.

PMID- 25757114
TI  - Exploring the characteristics of high-performing hospitals that influence trauma
      triage and transfer.
AB  - BACKGROUND: Many trauma patients might be first cared for at nondesignated
      centers before transfer to a trauma center. Limited research has investigated
      determinants of timely triage and transfer to identify those amenable to quality
      improvement. This study explored factors influencing timely triage and transfer
      in a regional trauma system. METHODS: Centers (n = 15) with both long and short
      transfer times (emergency department length of stay before transfer) in Ontario
      were identified using a regional trauma registry. Physicians and nurses in these
      centers were interviewed with a view to determining factors that either impeded
      or enabled rapid decisions regarding the need for transfer to a trauma center. A
      grounded theory approach and constant comparative technique were used to collect
      and analyze data. RESULTS: Nineteen physicians and eight nurses participated.
      Clinician level (experience, training, personality, fear of judgment, nursing
      role), institutional level (guidelines, continuing education, trauma
      infrastructure, human resources) and system-level (bed availability, referral
      center, air transport, communication with trauma centers) factors influenced
      timely decision making. Participants offered several recommendations to improve
      care. These included guidelines for transfer, a "no refusal" policy at trauma
      centers, improved air transport and referral center services, as well as further
      regionalization. Additional features of hospitals with shorter transfer times
      included coaching of new staff, team meetings, leadership engagement, sharing of
      performance data, and minimum work hours for physicians. CONCLUSION: Numerous
      interacting factors that may influence trauma triage and transfer were
      identified. These findings can be used by policy makers, health care managers,
      and clinicians in emergency departments or trauma centers to evaluate and improve
      trauma triage and transfer, or plan new services. The findings can also be used
      by researchers to examine the relevance of these factors in other settings or to
      implement and evaluate the impact of interventions informed by recommendations
      generated here.

PMID- 25757116
TI  - The impact of preexisting comorbidities on failure to rescue outcomes in
      nonelderly trauma patients.
AB  - BACKGROUND: Death after complication or "failure to rescue" (FTR) contributes to
      differences in risk-adjusted mortality rates among trauma centers and is
      considered an indicator of quality of care. Successful management of trauma
      patients requires not only appropriately responding to complications but also
      timely recognition of adverse events. Identifying associations between patient
      characteristics, such as the presence of comorbidities, and FTR outcomes can
      potentially improve early detection of complications and can reduce the risk of
      in-hospital mortality. METHODS: We performed a retrospective cohort study that
      analyzed patient records included in the National Trauma Data Bank from years
      2008 to 2010. Cox regression modeling was used to determine the contribution of
      individual comorbidities to FTR outcomes while controlling for confounding
      variables. RESULTS: Diabetes, congestive heart failure, history of myocardial
      infarction, and dialysis were associated with greater hazard ratios (HRs) (95%
      confidence interval [CI]) for FTR (1.19 [1.05-1.35], 1.63 [1.30-2.05], 1.40 [1.08
      1.81], 2.34 [1.72-3.19], respectively). Smoking, alcoholism, and respiratory
      disease were associated with a lower risk of FTR (HR [95% CI], 0.68 [0.60-0.77];
      0.88 [0.80-0.98]; and 0.77 [0.66-0.91], respectively). Obesity and hypertension
      were not associated with increased risk of FTR. CONCLUSION: Preexisting
      comorbidities contributed significantly to risk of death after complication in
      the trauma population. Identifying processes of care that lead to better
      management of complications in patients with comorbidities would improve trauma
      centers' overall mortality outcomes. LEVEL OF EVIDENCE: Prognostic study, level
      IV.

PMID- 25757115
TI  - The excess morbidity and mortality of emergency general surgery.
AB  - BACKGROUND: Emergency general surgery (EGS) carries a disproportionate burden of
      risk from medical errors, complications, and death compared with non-EGS (NEGS).
      Previous studies have been limited by patient and procedure heterogeneity but
      suggest worse outcome in EGS patients because of preoperative risk factors. The
      aim of this study was to quantify the excess burden of morbidity and mortality
      associated with EGS by controlling for patient-specific factors. We hypothesized
      that EGS is an independent risk factor for morbidity and mortality. METHODS: We
      retrospectively analyzed data from the American College of Surgeons-National
      Surgical Quality Improvement Program. Fourteen procedures common to both EGS and
      NEGS from 2008 through 2012 were included. Patients were stratified based on
      emergency status. The primary outcome was death within 30 days of operation.
      Secondary outcomes were postoperative complications. Variables from the American
      College of Surgeons-National Surgical Quality Improvement Program preoperative
      risk assessment were analyzed. chi and Wilcoxon signed-rank tests were used to
      compare variables. Multivariate logistic regression was used to identify
      independent risk factors for mortality and complications. RESULTS: Of 66,665
      patients, 24,068 were EGS and 42,597 were NEGS. Mortality was 12.50% for EGS
      patients and 2.66% for NEGS patients (p < 0.0001). Major complications occurred
      in 32.80% of EGS patients and 12.74% of NEGS patients (p < 0.0001). When
      preoperative variables and procedure type were controlled, EGS was independently
      associated with death (odds ratio, 1.39; p = 0.029) and major complications (odds
      ratio, 1.31; p = 0.001). CONCLUSION: EGS is an independent risk factor for death
      and postoperative complications. The excess morbidity and mortality of EGS are
      not fully explained by preoperative risk factors, making EGS an excellent target
      for quality improvement projects. LEVEL OF EVIDENCE: Prognostic/epidemiologic
      study, level III.

PMID- 25757117
TI  - Using the age-adjusted Charlson comorbidity index to predict outcomes in
      emergency general surgery.
AB  - BACKGROUND: We evaluated the role of the Charlson age-comorbidity index (CACI), a
      weighted comorbidity index that reflects cumulative increased likelihood of 1
      year mortality, in predicting perioperative outcomes in an emergency general
      surgery population at a large Canadian teaching hospital. METHODS: A
      retrospective chart review of emergency general surgery admissions in 2010 was
      conducted. Patients who had surgery were identified. Mode of surgery and CACI
      were recorded, as well as measures of outcome, including 30-day mortality and
      intensive care unit (ICU) admission. A multivariate stepwise logistic regression
      model was created to assess the effect of age-adjusted Charlson comorbidity index
      on postoperative outcomes while controlling for the effect of possible
      confounders. The prediction ability of CACI for mortality was assessed using
      receiver operating characteristic analyses considering the area under the curve
      and its 95% confidence intervals (CIs). RESULTS: Of the 529 admissions to general
      surgery from the emergency department, 257 patients underwent a surgical
      intervention. The CACI scores ranged from 0 to 16. We described a total of 11
      deaths (4.3%) and 30 ICU admissions (11.7%). CACI was associated with an
      increased risk of 30-day mortality (adjusted odds ratio,1.39; 95% CI, 1.11-1.73;
      p = 0.0034). Receiver operating characteristic analysis was consistent with high
      accuracy of CACI for mortality prediction alone, resulting in area under the
      curve or c statistic of 0.90 (95% CI, 0.84-0.95). CACI was similar in predicting
      mortality to a multivariate model. CACI was also found to be associated with ICU
      admission (adjusted odds ratio, 1.17; 95% CI, 1.01-1.37; p < 0.0382). CACI is not
      as good a predictor for ICU admission when compared with the multivariate model.
      CONCLUSION: We have shown that the CACI is a valid tool for 30-day mortality
      prediction in the context of emergency general surgery. LEVEL OF EVIDENCE:
      Prognostic study, level III.

PMID- 25757118
TI  - Efficacy of a prehospital self-expanding polyurethane foam for noncompressible
      hemorrhage under extreme operational conditions.
AB  - BACKGROUND: Noncompressible abdominal hemorrhage is a significant cause of
      battlefield and civilian mortality. We developed a self-expanding polyurethane
      foam intended to provide temporary hemorrhage control and enable evacuation to a
      definitive surgical capability, for casualties who would otherwise die. We
      hypothesized that foam treatment would be efficacious over a wide range of out-of
      hospital operational conditions. METHODS: The foam was tested in an established
      lethal, closed-cavity hepatoportal injury model in four groups as follows. Group
      1 involved baseline conditions, wherein foam was deployed from a pneumatically
      driven, first-generation delivery device at room temperature (n = 6). Group 2
      involved foam deployment from a field-relevant, handheld delivery prototype (n =
      12). Group 3 involved foam components that were conditioned to simulate 1-year
      shelf-life (n = 6). Group 4 involved foam that was conditioned to a range of
      temperatures (10  degrees C and 50  degrees C; n = 6 per group). In all studies,
      survival was monitored for up to 180 minutes and compared with an ongoing and
      accumulating control group with no intervention (n = 14). RESULTS: In Group 1
      with a first-generation delivery system, foam treatment resulted in a significant
      survival advantage relative to the control group (p < 0.001), confirming previous
      results. In Group 2 with a handheld delivery system, survival was also improved,
      83% at 3 hours, compared with 7% in the control group (p < 0.001). In Group 3,
      survival was 83% at 3 hours (p = 0.002). In Group 4 at temperature extremes, 3
      hour survival was 83% (p = 0.002) and 67% (p = 0.014) in the low- and high
      temperature groups, respectively. Temperature extremes did not result in
      hypothermia, hyperthermia, or thermal injury. In all studies, the bleeding rate
      in foam groups was significantly lower than in the control group (p < 0.05).
      CONCLUSION: Under a range of military operational conditions, foam treatment
      resulted in a survival advantage relative to the control group. This supports the
      feasibility of foam treatment as a prehospital hemostatic bridge to surgery for
      severely bleeding causalities.

PMID- 25757119
TI  - The effects of balanced blood component resuscitation and crystalloid
      administration in pediatric trauma patients requiring transfusion in Afghanistan
      and Iraq 2002 to 2012.
AB  - BACKGROUND: Component balanced resuscitation and avoidance of crystalloids in
      traumatically injured adults requiring massive transfusion are beneficial.
      Evidence for children is lacking. METHODS: After institutional review board
      approval was obtained, the Department of Defense Trauma Database identified 1,311
      injured children 14 years or younger requiring transfusion after an injury and
      admitted to a deployed US military hospital from 2002 to 2012. Logistic
      regression determined risk factors for high-volume (>=40 mL/kg) or massive (>=70
      mL/kg) transfusions. The effects of crystalloid and balanced component
      resuscitation in the first 24 hours were assessed. RESULTS: Nine hundred seven
      patients had recorded data sufficient for analysis. Two hundred twenty-four
      children received high-volume transfusion, and 77 received massive transfusions.
      Mortality was significantly higher for massive transfusions and high-volume
      transfusions than others (25% vs. 10% and 19% vs. 9%, respectively). Age of less
      than 4 years, penetrating injury, and Injury Severity Score (ISS) greater than 15
      were associated with high-volume transfusions; an ISS greater than 15 and
      penetrating injury were associated with massive transfusions. Increased
      crystalloid administration showed a significant positive association with
      hospital days and intensive care unit days for both massive and high-volume
      transfusions, as well as a significant positive association with increased
      ventilator days in patients with high-volume transfusions. Balanced component
      resuscitation was not associated with improved measured outcomes and was
      independently associated with a higher mortality when all transfused patients
      were considered. CONCLUSION: In this cohort, heavy reliance on crystalloid for
      resuscitation had an adverse effect on outcomes. Balanced component resuscitation
      did not improve outcomes and was associated with higher mortality when all
      transfused patients were considered. Further study is needed regarding efficacy
      and clinical triggers for the implementation of massive transfusion in children.
      LEVEL OF EVIDENCE: Prognostic study, level IV.

PMID- 25757120
TI  - Damage-control resuscitation increases successful nonoperative management rates
      and survival after severe blunt liver injury.
AB  - BACKGROUND: Nonoperative multidisciplinary management for severe (American
      Association for the Surgery of Trauma Grades IV and V) liver injury has been used
      for two decades. We have previously shown that Damage Control Resuscitation (DCR)
      using low-volume, balanced resuscitation improves survival of severely injured
      trauma patients; however, little attention has been paid to organ-specific
      outcomes. We wanted to determine if implementation of DCR has improved survival
      and successful nonoperative management after severe blunt liver injury. METHODS:
      A retrospective study was performed on all adult trauma patients with severe
      blunt liver injury who were admitted from 2005 to 2011. Patients were divided
      into pre-DCR (2005-2008) and DCR (2009-2011) groups. Patients who died before
      leaving the emergency department (ED) were excluded. Outcomes (resuscitation
      products used, survival, and length of stay) were then compared by univariate and
      multivariate analyses. RESULTS: Between 2005 and 2011, 29,801 adult trauma
      patients were admitted, and 1,412 (4.7%) experienced blunt liver injury. Of
      these, 244 (17%) sustained Grade IV and V injuries, with 206 patients surviving
      to leave the ED. The pre-DCR group (2005-2008) was composed of 108 patients, and
      the DCR group (2009-2011) had 98 patients. The groups were not different in
      demographics as well as prehospital and ED vital signs or Injury Severity Score
      (ISS). No change in operative or interventional radiology techniques occurred in
      this time frame. The DCR cohort had an increase in successful nonoperative
      management (from 54% to 74%, p < 0.01) as well as a reduction in initial 24-hour
      packed red blood cell (median, from 13 U to 6.5 U; p < 0.01), plasma (median,
      from 13 U to 8 U; p < 0.01), and crystalloid (median, from 5,800 mL to 4,100 mL;
      p < 0.01) administration. The DCR treatment was associated with improved
      survival, from 73% to 94% (p < 0.01). CONCLUSION: In patients with severe blunt
      liver injury, DCR was associated with less crystalloid and blood product use, a
      higher successful nonoperative management rate, and improved survival.
      Resuscitation technique may improve outcomes after severe liver injury. LEVEL OF
      EVIDENCE: Therapeutic/care management, level III.

PMID- 25757121
TI  - Understanding traumatic shock: out-of-hospital hypotension with and without other
      physiologic compromise.
AB  - BACKGROUND: Among trauma patients with out-of-hospital hypotension, we evaluated
      the predictive value of systolic blood pressure (SBP) with and without other
      physiologic compromise for identifying trauma patients requiring early critical
      resources. METHODS: This was a secondary analysis of a prospective cohort of
      injured patients 13 years or older with out-of-hospital hypotension (SBP <= 90 mm
      Hg) who were transported by 114 emergency medical service agencies to 56 Level I
      and II trauma centers in 11 regions of the United States and Canada from January
      1, 2010, through June 30, 2011. The primary outcome was early critical resource
      use, defined as blood transfusion of 6 U or greater, major nonorthopedic surgery,
      interventional radiology, or death within 24 hours. RESULTS: Of 3,337 injured
      patients with out-of-hospital hypotension, 1,094 (33%) required early critical
      resources and 1,334 (40%) had serious injury (Injury Severity Score [ISS] >= 16).
      Patients with isolated hypotension required less early critical resources (14%
      vs. 52%), had less serious injury (20% vs. 61%), and had lower mortality (24
      hours, 1% vs. 26%; in-hospital, 3% vs. 34%). The standardized probability of
      requiring early critical resources was lowest among patients with blunt injury
      and isolated moderate hypotension (0.12; 95% confidence interval, 0.09-0.15) and
      steadily increased with additional physiologic compromise, more severe
      hypotension, and penetrating injury (0.94; 95% confidence interval, 0.90-0.98).
      CONCLUSION: A minority of trauma patients with isolated out-of-hospital
      hypotension require early critical resuscitation resources. However, hypotension
      accompanied by additional physiologic compromise or penetrating injury markedly
      increases the probability of requiring time-sensitive interventions. LEVEL OF
      EVIDENCE: Prognostic study, level II.

PMID- 25757122
TI  - Systolic blood pressure criteria in the National Trauma Triage Protocol for
      geriatric trauma: 110 is the new 90.
AB  - BACKGROUND: Undertriage is a concern in geriatric patients. The National Trauma
      Triage Protocol (NTTP) recognized that systolic blood pressure (SBP) less than
      110 mm Hg may represent shock in those older than 65 years. The objective was to
      evaluate the impact of substituting an SBP of less than 110 mm Hg for the current
      SBP of less than 90 mm Hg criterion within the NTTP on triage performance and
      mortality. METHODS: Subjects undergoing scene transport in the National Trauma
      Data Bank (2010-2012) were included. The outcome of trauma center need was
      defined as Injury Severity Score (ISS) greater than 15, intensive care unit
      admission, urgent operation, or emergency department death. Geriatric (age > 65
      years) and adult (age, 16-65 years) cohorts were compared. Triage characteristics
      and area under the curve (AUC) were compared between SBP of less than 110 mm Hg
      and SBP of less than 90 mm Hg. Hierarchical logistic regression was used to
      determine whether geriatric patients newly triaged positive under this change
      (SBP, 90-109 mm Hg) have a risk of mortality similar to those triaged positive
      with SBP of less than 90 mm Hg. RESULTS: There were 1,555,944 subjects included.
      SBP of less than 110 mm Hg had higher sensitivity but lower specificity in
      geriatric (13% vs. 5%, 93% vs. 99%) and adult (23% vs. 10%, 90% vs. 98%) cohorts.
      AUC was higher for SBP of less than 110 mm Hg individually in both geriatric and
      adult (p < 0.01) cohorts. Within the NTTP, the AUC was similar for SBP of less
      than 110 mm Hg and SBP of less than 90 mm Hg in geriatric subjects but was higher
      for SBP of less than 90 mm Hg in adult subjects (p < 0.01). Substituting SBP of
      less than 110 mm Hg resulted in an undertriage reduction of 4.4% with overtriage
      increase of 4.3% in the geriatric cohort. Geriatric subjects with SBP of 90 mm Hg
      to 109 mm Hg had an odds of mortality similar to those of geriatric patients with
      SBP of less than 90 mm Hg (adjusted odds ratio, 1.03; 95% confidence interval,
      0.88-1.20; p = 0.71). CONCLUSION: SBP of less than 110 mm Hg increases
      sensitivity. SBP of less than 110 mm Hg has discrimination as good as that of SBP
      of less than 90 mm Hg, with superior improvements in undertriage relative to
      overtriage in geriatric patients. Geriatric patients newly triaged to be positive
      under this change have a risk of mortality similar to those under the current SBP
      criterion. This change in SBP criteria may be merited in geriatric patients,
      warranting further study to consider elevation to a Step 1 criterion in the NTTP.
      LEVEL OF EVIDENCE: Diagnostic study, level IV.

PMID- 25757123
TI  - Contemporary management and outcomes of blunt thoracic aortic injury: a
      multicenter retrospective study.
AB  - BACKGROUND: Blunt thoracic aortic injuries (BTAIs) are composed of a spectrum of
      lesions ranging from intimal tear to rupture, yet optimal management and ultimate
      outcome have not been clearly established. METHODS: This is a retrospective
      multicenter study of BTAIs from January 2008 to December 2013. Demographics,
      diagnosis, treatment, and in-hospital outcomes were analyzed. RESULTS: Nine
      American College of Surgeons-verified Level I trauma centers contributed data
      from 453 patients with BTAIs. After exclusion of patients expiring before imaging
      (58) and transfers (13), 382 patients with imaging diagnosis were available for
      analysis (Grade 1, 94; Grade 2, 68; Grade 3, 192; Grade 4, 28). Hypotension was
      present on admission in 56 (14.7%). Computed tomographic angiography was used for
      diagnosis in 94.5%. Nonoperative management (NOM) was selected in 32%, with two
      in-hospital failures (Grade 1, Grade 4) requiring endovascular salvage (thoracic
      endovascular aortic repair [TEVAR]). Open repair (OR) was completed in 61 (16%).
      TEVAR was conducted in 198 (52%), with 41% of these requiring left subclavian
      artery coverage. Complications of TEVAR included endograft malposition (6, 3.0%),
      endoleak (5, 2.5%), paralysis (1, 0.5%), and stroke (2, 1.0%). Six TEVAR failures
      were treated by repeat TEVAR (2) or OR (4). Overall in-hospital mortality was
      18.8%, and aortic-related mortality was 6.5% (NOM, 9.8%; OR, 13.1%; TEVAR, 2.5%)
      (Grade 1, 0%; Grade 2, 2.9%; Grade 3, 5.2%; Grade 4, 46.4%). The majority of
      aortic-related deaths (18 of 25) occurred before the opportunity for repair.
      Independent predictors of aortic-related mortality among BTAI patients were
      higher chest Abbreviated Injury Scale (AIS) score, grade, and Injury Severity
      Score (ISS); TEVAR was protective (p = 0.03; odds ratio, 0.21; confidence
      interval, 0.05-0.88). CONCLUSION: Failures and aortic-related mortality of NOM
      following BTAI Society of Vascular Surgery Grade 1 to 3 injuries are rare. TEVAR
      seems independently protective against aortic-related mortality. Early
      complications of TEVAR have decreased relative to previous reports. Prospective
      long-term follow-up data are required to better refine indications for
      intervention. LEVEL OF EVIDENCE: Level IV.

PMID- 25757124
TI  - The effect of cyclosporine A in hemorrhagic shock model of rats.
AB  - BACKGROUND: The inhibition of mitochondrial permeability transition pore opening
      during ischemia-reperfusion can ameliorate injuries. This study aimed to
      investigate the effects of cyclosporine A (CsA) in rats after hemorrhagic shock.
      METHODS: Male Sprague-Dawley rats were subjected to pressure-controlled
      hemorrhagic shock (mean arterial pressure, 38 +/- 1 mm Hg) for 90 minutes. After
      the hemorrhagic shock period, rats were randomly allocated to one of three groups
      as follows: a control group, a CsA10 group, or a CsA50 group. CsA for the
      treatment groups (10 mg/kg for the CsA10 group and 50 mg/kg for the CsA50 group)
      or normal saline for the control group was administered via tail vein for 10
      minutes, and shed blood was transfused for 15 minutes. For the survival study,
      animals were observed for up to 9 hours, and their survival time was recorded
      until death. Separate experiments were performed to examine the effect of CsA on
      inflammatory responses and liver injury. Rats were sacrificed at 210 minutes
      after the shock period, and blood and liver tissues were harvested. RESULTS:
      Survival times were shown to be significantly longer in the CsA-treated groups
      (i.e., the CsA10 and CsA50 groups) than in the control group. Plasma interleukin
      6 and thiobarbituric acid-reactive substances were significantly lower in the
      CsA50 group than in the control group and phosphorylation of Akt, GSK-3beta, and
      Bad were significantly increased in the CsA-treated groups compared with the
      control group. Expressions of Bcl-2, cleaved caspase 3, and cytoplasmic
      cytochrome C were significantly decreased in the CsA-treated groups compared with
      the control group. Although histologic liver injury was not significantly
      different among the groups, ultrastructural changes of mitochondria were more
      prominent in the control group than in the CsA-treated groups. CONCLUSION: CsA
      increased survival time, decreased proinflammatory cytokine and lipid
      peroxidation, and augmented Akt survival pathways in rats subjected to pressure
      controlled hemorrhagic shock.

PMID- 25757125
TI  - Inhibition of histone deacetylase 6 improves long-term survival in a lethal
      septic model.
AB  - BACKGROUND: We recently demonstrated that suberoylanilide hydroxamic acid, a
      broad-spectrum histone deacetylase (HDAC) inhibitor that inhibits HDACs 1, 2, 3,
      and 6, improves survival in a mouse model of cecal ligation and puncture (CLP)
      induced lethal sepsis. The current study was undertaken to determine the effect
      of selective inhibition of HDAC isoform on survival, key cytokine production,
      organ injury, bacteria clearance, and cell apoptosis. METHODS: In Experiment 1,
      C57BL/6J mice were subjected to CLP and, 1 hour later, given intraperitoneal
      injections of (1) Tubastatin A (inhibitor of HDAC6) dissolved in dimethyl
      sulfoxide (DMSO), (2) MS-275 (inhibitor of HDACs 1, 2, and 3) in DMSO, and (3)
      DMSO only. Survival was monitored for 10 days. In Experiment 2, 1 hour after CLP,
      animals were treated with DMSO vehicle or Tubastatin A. Sham-operated animals
      served as control. Peritoneal fluid and blood samples were collected for
      measurement of cytokines at 24 hours or 48 hours. Blood at 48 hours was also used
      to determine bacteria load. Liver was harvested to evaluate acute liver injury.
      In Experiment 3, Primary splenocytes were used to assess cytokine responses and
      phagocytosis. Macrophages were cultured and harvested 3 hours and 6 hours after
      lipopolysaccharide stimulation in the absence or presence of Tubastatin A to
      analyze cell apoptosis. RESULTS: Animals treated with Tubastatin A, but not MS
      275, displayed a significant improvement in survival. Moreover, Tubastatin A
      significantly inhibited cytokine production in peritoneal fluid and plasma as
      well as in supernatant from splenocytes stimulated with lipopolysaccharide.
      Tubastatin A significantly attenuated acute liver injury, increased blood
      bacteria clearance and splenocyte phagocytosis, and decreased macrophage
      apoptosis. CONCLUSION: HDAC6 inhibition significantly improves survival, reduces
      "cytokine storm," attenuates acute livery injury, increases bacteria clearance
      and immune cell phagocytosis, and inhibits macrophage apoptosis in a lethal mouse
      CLP model.

PMID- 25757126
TI  - Does chest tube location matter? An analysis of chest tube position and the need
      for secondary interventions.
AB  - BACKGROUND: Tube thoracostomy is a common procedure used in the management of
      thoracic trauma. Traditional teaching suggests that chest tubes should be
      directed in specific locations to improve function. Common examples include
      anterior and superior placement for pneumothorax, inferior and posterior
      placement for hemothorax, and avoidance of the pulmonary fissure. The purpose of
      this study was to examine the effect of specific chest tube position on
      subsequent chest tube function. METHODS: A retrospective review of all patients
      undergoing tube thoracostomy for trauma from January 1, 2010, to September 30,
      2012, was performed. Only patients undergoing computed tomography scans following
      chest tube insertion were included so that positioning could be accurately
      determined. Rib space insertion level and positioning of the tube relative to the
      lung parenchyma were recorded. The duration of chest tube drainage and the need
      for secondary interventions were determined and compared for tubes in different
      rib spaces and locations. For purposes of comparison, tubes placed above the
      sixth rib space were considered "high," and those at or below it were considered
      "low." RESULTS: A total of 291 patients met criteria for inclusion. Forty-eight
      patients (16.5%) required secondary intervention. Neither high chest tube
      placement nor chest tube location relative to lung parenchyma was associated with
      an increased need for secondary interventions. On multivariate analysis, only
      chest Abbreviated Injury Scale (AIS) scores, mechanism, and volume of hemothorax
      were found to be significant risk factors for the need for secondary
      interventions. CONCLUSION: Chest tube location does not influence the need for
      secondary interventions as long as the tube resides in the pleural space. The
      severity of chest injury is the most important factor influencing outcome in
      patients undergoing tube thoracostomy for trauma. Tube thoracostomy technique
      should focus on safe insertion within the pleural space and not on achieving a
      specific tube location. LEVEL OF EVIDENCE: Therapeutic study, level IV.

PMID- 25757127
TI  - Natural history of a postpull pneumothorax or effusion: observation is safe.
AB  - BACKGROUND: Thoracostomy tube (TT) for drainage of hemopneumothorax is the most
      common intervention in thoracic trauma. Postpull pneumothorax or effusion
      (PPP/PPE) is common after removal of a TT. The natural history of PPP/PPE after
      discharge has not been described. This study evaluates the outcomes and
      management of PPP/PPE after discharge. METHODS: Trauma patients with TT placed
      from July 1, 2008, to June 30, 2013, were identified from an administrative
      database and trauma registry. PPP/PPE was defined as the presence of air or fluid
      in the chest on a postpull imaging. The electronic medical record and final
      radiology interpretation were reviewed to confirm PPP/PPE during index admission
      and at discharge. Clinical follow-up and imaging were reviewed for the presence
      of persistent PPP/PPE. Interventions directed toward PPP/PPE and readmissions
      were recorded for patients with and without a PPP/PPE. Multivariate logistic
      regression was performed to identify factors for chest-related readmission.
      RESULTS: Seven hundred ten patients surviving to discharge had a TT placed during
      the study time frame. Of the 151 patients (21.3%) with documented PPP/PPE on
      discharge, 115 patients had follow-up data available. Outpatient imaging was
      obtained in 35 patients, with persistent PPP/PPE noted in 16 patients (45.7%).
      Six patients (4%) with PPP/PPE at discharge required reintervention. Patients
      without documented PPP/PPE at discharge had a lower readmission rate (0.7% vs.
      6.6%, p = 0.02). Multivariate logistic regression noted the presence of
      persistent PPP/PPE at follow-up (p = 0.001) to be associated with readmission.
      CONCLUSION: PPP/PPE is a common occurrence following removal of a TT. While
      patients discharged with PPP/PPE have a statistically higher reintervention rate,
      the absolute value remains low. This should be considered when treating
      clinically stable, asymptomatic PPP/PPE. LEVEL OF EVIDENCE: Epidemiologic study,
      level IV.

PMID- 25757128
TI  - Hospital-acquired pneumonia is an independent predictor of poor global outcome in
      severe traumatic brain injury up to 5 years after discharge.
AB  - BACKGROUND: Long-term outcomes following traumatic brain injury (TBI) correlate
      with initial head injury severity and other acute factors. Hospital-acquired
      pneumonia (HAP) is a common complication in TBI. Limited information exists
      regarding the significance of infectious complications on long-term outcomes
      after TBI. We sought to characterize risks associated with HAP on outcomes 5
      years after TBI. METHODS: This study involved data from the merger of an
      institutional trauma registry and the Traumatic Brain Injury Model Systems
      outcome data. Individuals with severe head injuries (Abbreviated Injury Scale
      [AIS] score >= 4) who survived to rehabilitation were analyzed. Primary outcome
      was Glasgow Outcome Scale-Extended (GOSE) at 1, 2, and 5 years. GOSE was
      dichotomized into low (GOSE score < 6) and high (GOSE score >= 6). Logistic
      regression was used to determine adjusted odds of low GOSE score associated with
      HAP after controlling for age, sex, head and overall injury severity, cranial
      surgery, Glasgow Coma Scale (GCS) score, ventilation days, and other important
      confounders. A general estimating equation model was used to analyze all outcome
      observations simultaneously while controlling for within-patient correlation.
      RESULTS: A total of 141 individuals met inclusion criteria, with a 30% incidence
      of HAP. Individuals with and without HAP had similar demographic profiles,
      presenting vitals, head injury severity, and prevalence of cranial surgery.
      Individuals with HAP had lower presenting GCS score. Logistic regression
      demonstrated that HAP was independently associated with low GOSE scores at follow
      up (1 year: odds ratio [OR], 6.39; 95% confidence interval [CI], 1.76-23.14; p =
      0.005) (2 years: OR, 7.30; 95% CI, 1.87-27.89; p = 0.004) (5-years: OR, 6.89; 95%
      CI, 1.42-33.39; p = 0.017). Stratifying by GCS score of 8 or lower and early
      intubation, HAP remained a significant independent predictor of low GOSE score in
      all strata. In the general estimating equation model, HAP continued to be an
      independent predictor of low GOSE score (OR, 4.59; 95% CI, 1.82-11.60; p =
      0.001). CONCLUSION: HAP is independently associated with poor outcomes in severe
      TBI extending 5 years after injury. This suggests that precautions should be
      taken to reduce the risk of HAP in individuals with severe TBI. LEVEL OF
      EVIDENCE: Prognostic study, level III.

PMID- 25757129
TI  - Adverse effects of admission blood alcohol on long-term cognitive function in
      patients with traumatic brain injury.
AB  - BACKGROUND: Alcohol is known to be protective in patients with traumatic brain
      injury (TBI); however, its impact on the long-term cognitive function is unknown.
      We hypothesize that intoxication at the time of injury is associated with adverse
      long-term cognitive function in patients sustaining TBI. METHODS: We performed a
      2-year retrospective study of all trauma patients with isolated TBI presenting to
      our Level I trauma center and discharged to a single rehabilitation facility.
      Patients with moderate-to-severe TBI (head Abbreviated Injury Scale [AIS] score
      >= 3), measured admission blood alcohol concentration, and measured cognitive
      function on hospital discharge and rehabilitation center discharge were included.
      Cognitive function was assessed using Functional Independence Measure (FIM)
      scores. Delta cognitive FIM was defined as the difference between rehabilitation
      center discharge and hospital discharge cognitive FIM scores. Multivariate linear
      regression was performed. RESULTS: A total of 64 patients were included. Mean
      (SD) age was 51.8 (23) years, median head AIS score was 3 (IQR, 3-5), and median
      Glasgow Coma Scale (GCS) score was 11 (IQR, 3-15). Mean (SD) cognitive FIM score
      on hospital discharge was 17 (6), and mean (SD) cognitive improvement was 8.6
      (4.7). Sixty percent (n = 39) were under the influence of alcohol on admission,
      and the mean (SD) admission blood alcohol concentration was 132 (102).On
      multivariate linear regression analysis, admission blood alcohol concentration
      (beta = -0.4; 95% confidence interval, -6.7 to -0.8; p = 0.01) and age (beta = 
      0.13; 95% confidence interval, -0.2 to -0.04; p = 0.04) were negatively
      associated with improvement in long-term cognitive function. CONCLUSION: Alcohol
      intoxication at the time of injury is associated with lower improvement in long
      term cognitive function. Older intoxicated patients are likely to have a lower
      cognitive improvement. LEVEL OF EVIDENCE: Prognostic and epidemiologic study,
      level III.

PMID- 25757130
TI  - An analysis of geriatric recidivism in the era of accountable care organizations.
AB  - BACKGROUND: To date, there are almost 500 accountable care organizations (ACOs)
      across the United States emphasizing cost-effective care. Readmission largely
      impacts health care cost; therefore, we sought to determine factors associated
      with geriatric trauma readmissions (recidivism) within our institution. METHODS:
      All admissions from 2000 to 2011 attributed to patients 65 years or older at our
      Level II trauma center, recently verified by Medicare as an ACO, were queried.
      Patients were classified as recidivist or nonrecidivist. The first admissions of
      recidivist patients were compared with the nonrecidivist admissions with respect
      to sex, age, race, primary insurance, admission Glasgow Coma Scale (GCS) score,
      Injury Severity Score (ISS), hospital length of stay, mechanism of injury (MOI),
      preexisting conditions, and discharge destination. Factors found to be
      significant predictors of recidivism in univariate analyses were subsequently
      incorporated into a multivariate logistic regression model. In addition, the
      second admission's MOI was compared with the first admission's MOI, and the
      proportion of first, second, and third admissions attributed to falls was
      calculated. A p < 0.05 was significant. RESULTS: Between 2000 and 2011, a total
      of 4,963 unique patients were admitted to the trauma center at 65 years or older.
      This population was composed of 287 recidivists (5.8%) and 4,676 nonrecidivists
      (94.2%). When placed in a multivariate logistic regression, female sex, admission
      GCS score of 15, history of head trauma, and preexisting pulmonary disease were
      identified as significant predictors of recidivism. A trend toward increasing
      proportion of injuries attributed to falls was found with each subsequent trauma
      admission (81.5% [234 of 287] of first admissions, 88.2% [253 of 287] of second
      admissions, and 90.5% [19 of 21] of third admissions). CONCLUSION: Our study
      identifies specific factors that should be targeted by social service and
      prevention resources to inhibit recidivism in the elderly. In the brave new world
      of ACOs, trauma centers must identify high-risk populations for the consumption
      of limited resources. LEVEL OF EVIDENCE: Care management study, level IV.
      Prognostic study, level III.

PMID- 25757131
TI  - Combating terror: a new paradigm in student trauma education.
AB  - BACKGROUND: Other than the Advanced Trauma Life Support course, usually run for
      postgraduate trainees, there are few trauma courses available for medical
      students. It has been shown that trauma teaching for medical students is sadly
      lacking within the undergraduate curriculum. We stated that students following
      formal teaching, even just theory and some practice in basic skills significantly
      improved their management of trauma patients. METHODS: Hadassah-Hebrew University
      in Israel runs an annual 2-week trauma course for final-year medical students.
      The focus is on hands-on practice in resuscitation, diagnosis, procedures, and
      decision making. After engaging a combination of instructional and interactive
      teaching methods including practice on simulated injuries that students must
      assess and treat through the 2 weeks, the course culminates in a disaster drill
      where students work alongside the emergency services to rescue, assess, treat,
      and transfer patients. The course is evaluated with a written precourse and
      postcourse test, an Objective Structured Clinical Examination and detailed
      feedback from the drill. RESULTS: We analyzed student feedback at the end of each
      course during a 6-year period from 2007 to 2012. Correct answers for the posttest
      results were higher each year with good reliability as assessed by Chronbach's
      alpha and with significant variation from pretest scores assessed using paired
      samples t tests. Best scores were achieved in knowledge acquisition and practical
      skills gained. Students were also asked whether the course contributed to self
      preparedness in treating trauma patients, and this consistently achieved high
      scores. CONCLUSION: We believe that students benefit substantially from the
      course and gain lasting skills and confidence in trauma management, decision
      making, and organizational skills. The course provides students with the
      opportunity to learn and ingrain trauma principles along Advanced Trauma Life
      Support guidelines and prepares them for practice as safe doctors. We advocate
      the global implementation of a student trauma training course as a mandatory
      educational initiative and propose our course format as a model for similar
      courses.

PMID- 25757132
TI  - Posterior component separation and transversus abdominis muscle release for
      complex incisional hernia repair in patients with a history of an open abdomen.
AB  - BACKGROUND: The best reconstructive approach for large fascial defects
      precipitated from a previous open abdomen has not been elucidated to date. We use
      a posterior component separation with transversus abdominis muscle release (TAR)
      in this scenario. METHODS: Patients with a history of an open abdomen who
      ultimately underwent complex hernia repair with TAR from 2010 to 2013 at Case
      Medical Center were identified in our prospective database and analyzed. RESULTS:
      Of 34 patients (mean [SD] age, 54 [11.3] years; mean [SD] body mass index, 32.5
      [7.2]) with a history of an open abdomen, the fascia was closed primarily in 11
      and skin alone closed primarily in 4 patients after a mean (SD) of 5.9 (6.7)
      days. Those unable to achieve primary closure either received a skin graft (n =
      16) or healed by secondary intention (n = 3). Patients presented to our
      institution a mean (SD) of 25.1 (26.5) months after their initial operation,
      eight having already undergone at least one hernia repair, including four
      anterior component separations. Operations consisted of 21 (61.8%) contaminated
      cases, including 7 enterocutaneous fistula takedowns, 2 stoma revisions, 2 stoma
      reversals, and 3 excisions of infected mesh. Wound morbidity consisted of 12
      (35%) surgical site occurrences: 1 wound dehiscence, 2 hematomas, 1 seroma, 8
      surgical site infections (23.5%; 3 superficial, 3 deep, and 2 organ space), and
      no enterocutaneous fistulas or chronic mesh infections. One reoperation was
      necessary for debridement of a hematoma and deep surgical site infection. With a
      mean follow-up of 18 months (range, 3-42 months), two (5.9%) new parastomal
      hernias and three (8.8%) midline recurrences have been documented. CONCLUSION: To
      our knowledge, this is the first report describing the use of TAR in patients
      with a history of an open abdomen for definitive abdominal wall reconstruction.
      We have demonstrated that this approach is associated with low significant
      perioperative morbidity and recurrence. LEVEL OF EVIDENCE: Therapeutic study,
      level V.

PMID- 25757134
TI  - Tourniquet application training for individuals with and without a medical
      background in a hospital setting.

PMID- 25757137
TI  - Oral health status in children and adolescents with haemophilia.
AB  - This case-controlled study aimed to evaluate the existing oral health status in
      children and adolescents with haemophilia. A total of 50 haemophilia patients and
      50 matched controls aged seven to 16 years were recruited into the study.
      Clinical examination was carried out to determine dental caries experience, oral
      hygiene status and gingival condition in these two groups. Information regarding
      previous dental history, oral hygiene practices and dietary habits were also
      obtained. No significant difference was found in mean caries experience in
      primary and secondary dentitions (P = 0.86 and 0.32) and in Simplified Oral
      Hygiene Index (OHI-S, P = 0.20) between both groups. However, a significantly
      higher proportion of haemophilia patients (24%) had better oral hygiene status as
      compared to the controls (2%, P = 0.004). Furthermore, there was a significant
      difference in Modified Gingival Index (MGI, P = 0.02) between the two groups with
      the study group having less gingival inflammation. A total of 88% (n = 44) of the
      haemophilia patients were registered and received dental treatment in specialist
      dental clinics. More than half (56%, n = 28) had frequent dental visits and only
      one-third of the haemophilia patients had history of hospitalization due to oral
      problems. There was no significant difference in oral hygiene practices and
      dietary habits between both groups. In general, haemophilia children and
      adolescents in this study had similar caries experience, a significantly better
      oral hygiene status and gingival health as compared to healthy controls. The main
      reason for this is the multidisciplinary approach implemented by medical health
      care professionals as primary care provider and the dental team.

PMID- 25757133
TI  - Cervical spine collar clearance in the obtunded adult blunt trauma patient: a
      systematic review and practice management guideline from the Eastern Association
      for the Surgery of Trauma.
AB  - BACKGROUND: With the use of the framework advocated by the Grading of
      Recommendations Assessment, Development and Evaluation (GRADE) Working Group, our
      aims were to perform a systematic review and to develop evidence-based
      recommendations that may be used to answer the following PICO [Population,
      Intervention, Comparator, Outcomes] question:In the obtunded adult blunt trauma
      patient, should cervical collar removal be performed after a negative high
      quality cervical spine (C-spine) computed tomography (CT) result alone or after a
      negative high-quality C-spine CT result combined with adjunct imaging, to reduce
      peri-clearance events, such as new neurologic change, unstable C-spine injury,
      stable C-spine injury, need for post-clearance imaging, false-negative CT imaging
      result on re-review, pressure ulcers, and time to cervical collar clearance?
      METHODS: Our protocol was registered with the PROSPERO international prospective
      register of systematic reviews on August 23, 2013 (REGISTRATION NUMBER:
      CRD42013005461). Eligibility criteria consisted of adult blunt trauma patients 16
      years or older, who underwent C-spine CT with axial thickness of less than 3 mm
      and who were obtunded using any definition.Quantitative synthesis via meta
      analysis was not possible because of pre-post, partial-cohort, quasi-experimental
      study design limitations and the consequential incomplete diagnostic accuracy
      data. RESULTS: Of five articles with a total follow-up of 1,017 included
      subjects, none reported new neurologic changes (paraplegia or quadriplegia) after
      cervical collar removal. There is a worst-case 9% (161 of 1,718 subjects in 11
      studies) cumulative literature incidence of stable injuries and a 91% negative
      predictive value of no injury, after coupling a negative high-quality C-spine CT
      result with 1.5-T magnetic resonance imaging, upright x-rays, flexion-extension
      CT, and/or clinical follow-up. Similarly, there is a best-case 0% (0 of 1,718
      subjects in 11 studies) cumulative literature incidence of unstable injuries
      after negative initial imaging result with a high-quality C-spine CT. CONCLUSION:
      In obtunded adult blunt trauma patients, we conditionally recommend cervical
      collar removal after a negative high-quality C-spine CT scan result alone. LEVEL
      OF EVIDENCE: Systematic review, level III.

PMID- 25757138
TI  - JIPB Board, supporting the plant science community through teamwork.

PMID- 25757140
TI  - Comparison of intraplatelet reactive oxygen species, mitochondrial damage, and
      platelet apoptosis after implantation of three continuous flow left ventricular
      assist devices: HeartMate II, Jarvik 2000, and HeartWare.
AB  - Differences in device design may have an effect on platelet damage and associated
      clinical complications. We aimed to compare device-specific platelet
      functionality in 26 heart failure patients supported with three continuous-flow
      left ventricular assist devices: HeartMate II (n = 8), Jarvik 2000 (n = 9), and
      HeartWare (n = 9). Intraplatelet reactive oxygen species (ROS) generation,
      mitochondrial damage, and platelet apoptosis were compared between device types
      before and after the implantation at every week up to 1 month. Overall, the
      baseline characteristics, demographics, routine laboratory values were comparable
      between the three device groups. Intraplatelet ROS, mitochondrial damage, and
      platelet apoptosis significantly elevated in the HeartWare group in comparison
      with the other two device groups after implantation. The major bleeding,
      infections, systemic inflammatory response syndrome, and right ventricular
      failure were found to be more common among the HeartWare group than others.
      Intraplatelet ROS and platelet damage levels were returned to baseline in both
      the HeartMate II and the Jarvik groups, whereas in HeartWare group they remained
      elevated. The patients with the Jarvik and the HeartMate II experienced less
      clinical complications and the platelet functionality is not compromised by these
      devices. Data from this study suggests that the continuous-flow left ventricular
      assist devices design may exert different effects on platelet function.

PMID- 25757139
TI  - Implementation of a cystic fibrosis lung transplant referral patient decision aid
      in routine clinical practice: an observational study.
AB  - BACKGROUND: The decision to have lung transplantation as treatment for end-stage
      lung disease from cystic fibrosis (CF) has benefits and serious risks. Although
      patient decision aids are effective interventions for helping patients reach a
      quality decision, little is known about implementing them in clinical practice.
      Our study evaluated a sustainable approach for implementing a patient decision
      aid for adults with CF considering referral for lung transplantation. METHODS: A
      prospective pragmatic observational study was guided by the Knowledge-to-Action
      Framework. Healthcare professionals in all 23 Canadian CF clinics were eligible.
      We surveyed participants regarding perceived barriers and facilitators to patient
      decision aid use. Interventions tailored to address modifiable identified
      barriers included training, access to decision aids, and conference calls. The
      primary outcome was >80% use of the decision aid in year 2. RESULTS: Of 23 adult
      CF clinics, 18 participated (78.2%) and 13 had healthcare professionals attend
      training. Baseline barriers were healthcare professionals' inadequate knowledge
      for supporting patients making decisions (55%), clarifying patients' values for
      outcomes of options (58%), and helping patients handle conflicting views of
      others (71%). Other barriers were lack of time (52%) and needing to change how
      transplantation is discussed (42%). Baseline facilitators were healthcare
      professionals feeling comfortable discussing bad transplantation outcomes (74%),
      agreeing the decision aid would be easy to experiment with (71%) and use in the
      CF clinic (87%), and agreeing that using the decision aid would not require
      reorganization of the CF clinic (90%). After implementing the decision aid with
      interventions tailored to the barriers, decision aid use increased from 29% at
      baseline to 85% during year 1 and 92% in year 2 (p < 0.001). Compared to
      baseline, more healthcare professionals at the end of the study were confident in
      supporting decision-making (p = 0.03) but continued to feel inadequate ability
      with supporting patients to handle conflicting views (p = 0.01). CONCLUSION: Most
      Canadian CF clinics agreed to participate in the study. Interventions were used
      to target identified modifiable barriers to using the patient decision aid in
      routine CF clinical practice. CF clinics reported using it with almost all
      patients in the second year.

PMID- 25757141
TI  - ALK translocation detection in non-small cell lung cancer cytological samples
      obtained by TBNA or EBUS-TBNA.
AB  - OBJECTIVE: As the diagnosis of non-small cell lung cancer (NSCLC) is based on
      cytology in around 70% of cases, it is important to use the same material for
      molecular analyses. Fluorescence in situ hybridization (FISH) is the only
      approved test for the detection of the translocation and inversion of anaplastic
      lymphoma kinase (ALK), but the optimal procedures for the fixation or staining of
      the sample before FISH evaluation have not been established. We investigated
      whether ALK gene status determined by FISH in a prospectively enrolled case
      series of patients was affected by fixation and staining. METHODS: One hundred
      and fifteen cytological samples were obtained by transbronchial needle aspiration
      (TBNA) or endobronchial ultrasound (EBUS)-TBNA from 109 patients with NSCLC. All
      samples were evaluated for epidermal growth factor receptor (EGFR) mutation by
      pyrosequencing and for ALK rearrangement by FISH. Specimens for ALK determination
      had been fixed with Cytofix((r)) and/or Carnoy's solution or 10% formalin (cell
      blocks) and variously stained. RESULTS: Sixteen (14%) of the 115 samples were
      mutated for EGFR and 99 (86%) showed wild-type EGFR status. Of these 115 samples,
      79 (69%) were negative for echinoderm microtubule-associated protein like 4
      (EML4)-ALK translocation, nine (8%) were positive and 27 (23%) were unevaluable.
      In particular, 19 (26%) of the 72 Papanicolaou-stained smears fixed with Cytofix
      were unevaluable because of inadequate samples or cell overlapping; neither of
      the two May-Grunwald-Giemsa-stained samples were evaluable. Ten of 17 smears used
      for rapid on-site evaluation (ROSE) and immediately post-fixed in Carnoy's
      solution or 80% alcohol were evaluable. CONCLUSIONS: In this series, smears were
      unevaluable as a result of inadequate samples, cell overlapping or lack of
      fixation performed immediately after FNA.

PMID- 25757142
TI  - Enhancing the Sensitivity of Pharmacophore-Based Virtual Screening by
      Incorporating Customized ZBG Features: A Case Study Using Histone Deacetylase 8.
AB  - As key regulators of epigenetic regulation, human histone deacetylases (HDACs)
      have been identified as drug targets for the treatment of several cancers. The
      proper recognition of zinc-binding groups (ZBGs) will help improve the accuracy
      of virtual screening for novel HDAC inhibitors. Here, we developed a high
      specificity ZBG-based pharmacophore model for HDAC8 inhibitors by incorporating
      customized ZBG features. Subsequently, pharmacophore-based virtual screening led
      to the discovery of three novel HDAC8 inhibitors with low micromole IC50 values
      (1.8-1.9 MUM). Further studies demonstrated that compound H8-A5 was selective for
      HDAC8 over HDAC 1/4 and showed antiproliferation activity in MDA-MB-231 cancer
      cells. Molecular docking and molecular dynamic studies suggested a possible
      binding mode for H8-A5, which provides a good starting point for the development
      of HDAC8 inhibitors in cancer treatment. 

PMID- 25757143
TI  - Coordination cluster nuclearity decreases with decreasing rare earth ionic radius
      in 1:1 Cr/Ln N-butyldiethanolamine compounds: a journey across the lanthanide
      series from Cr4(III)La4-Cr4(III)Tb4 via Cr3(III)Dy3 and Cr3(III)Ho3 to
      Cr2(III)Er2-Cr2(III)Lu2.
AB  - Reactions of the N-substituted diethanolamine ligand N-n-butyldiethanolamine with
      chromium(II) and lanthanide(III)/rare earth salts (Ln = La, Ce, Pr, Nd, Sm, Eu,
      Gd, Tb, Dy, Ho, Er, Tm, Yb, Lu, Y) in the presence of coligands give access to
      three series of isostructural 1:1 3d(Cr(III))/4f(Ln(III)) coordination cluster
      compounds that can be designated in terms of octanuclear "square-in-square" (Ln =
      La-Tb), hexanuclear "triangle-in-triangle" (Ln = Dy, Ho, Y) and tetranuclear
      "butterfly" or defect dicubane core (Ln = Er-Lu) topologies as revealed by single
      crystal X-ray crystallographic analysis. The bulk magnetic properties were also
      measured. The influences of the various components in the reaction system on the
      final topology and the role of the ionic radius are discussed. 

PMID- 25757144
TI  - X-Band DNP Hyperpolarization of Viscous Liquids and Polymer Melts.
AB  - NMR studies of synthetic polymers and biomacromolecules, which provide insight
      into the conformation and dynamics of these materials, can benefit strongly from
      the increased sensitivity offered by dynamic nuclear polarization (DNP) and other
      hyperpolarizing methods. In this study (1) H DNP nuclear spin hyperpolarization
      of two polybutadiene samples, representing a supercooled liquid and an entangled
      polymer melt, is demonstrated at 0.35 T magnetic field strength and at
      temperatures between -80 and +50  degrees C. Electron spin polarization transfer
      from the alpha,gamma-bisdiphenylene-beta-phenylallyl radical to the sample nuclei
      is achieved by the Overhauser and solid effect. DNP signal enhancements are
      studied, varying the electron spin resonance offset, microwave power, and sample
      temperature. The influence of spin relaxation times, line widths, and molecular
      dynamics are discussed. The results show promising, up to 15-fold NMR signal
      enhancements using noncryogenic temperatures and an inexpensive setup that is
      less technically demanding than current high-field DNP setups. 

PMID- 25757145
TI  - Antimicrobial photodynamic inactivation of Staphylococcus aureus biofilms in bone
      specimens using methylene blue, toluidine blue ortho and malachite green: An in
      vitro study.
AB  - OBJECTIVE: To evaluate the in vitro effectiveness of APDI with a 660 nm laser
      combined with methylene blue (MB), toluidine blue ortho (TBO) and malachite green
      (MG) dyes to inactivate Staphylococcus aureus (ATCC 25923) biofilms in compact
      and cancellous bone specimens. METHODS: Eighty specimens of compact and 80 of
      cancellous bone were contaminated with a standard suspension of the microorganism
      and incubated for 14 days at 37 degrees C to form biofilms. After this period,
      the specimens were divided into groups (n=10) according to established treatment:
      PS-L- (control - no treatment); PSmb+L-, PStbo+L-, PSmg+L- (only MB, TBO or MG
      for 5 min in the dark); PS-L+ (only laser irradiation for 180 s); and APDImb,
      APDItbo and APDImg (APDI with MB, TBO or MG for 180 s). The findings were
      statistically analyzed by ANOVA at 5% significance levels. RESULTS: All
      experimental treatments showed significant reduction of log CFU/mL S. aureus
      biofilms when compared with the control group for compact and cancellous bones
      specimens; the APDI group's treatment was more effective. The APDI carried out
      for the compact specimens showed better results when compared with cancellous
      specimens at all times of application. For the group of compact bone, APDImg
      showed greater reductions in CFU/mL (4.46 log 10). In the group of cancellous
      bone, the greatest reductions were found in the APDImb group (3.06 log 10).
      CONCLUSION: APDI with methylene blue, toluidine blue ortho and malachite green
      dyes and a 660 nm laser proved to be effective in the inactivation of S. aureus
      biofilms formed in compact and cancellous bone.

PMID- 25757146
TI  - Experimental low-level jaw clenching inhibits temporal summation evoked by
      electrical stimulation in healthy human volunteers.
AB  - OBJECTIVE: To examine the effect of low-level jaw clenching on temporal summation
      in healthy volunteers. DESIGN: In 18 healthy volunteers, the pain intensities
      evoked at the masseter muscle and the hand palm by the first and last stimuli in
      a train of repeated electrical stimuli (0.3 or 2.0 Hz) were rated using 0-100mm
      visual analogue scales (VAS), in order to evaluate temporal summation before and
      after three types of jaw-muscle tasks: low-level jaw clenching, repetitive gum
      chewing and mandibular rest position. A set of concentric surface electrodes with
      different diameters (small and large) was used for the electrical stimulation.
      RESULTS: The temporal summation evoked by the large diameter electrode with 2.0
      Hz stimulation decreased significantly both on the masseter and the hand after
      low-level clenching (P <= 0.03), but did not show any significant change after
      the other tasks (P > 0.23). The VAS score of the first stimulation did not show
      any significant changes after low-level clenching (P > 0.57). CONCLUSIONS:
      Experimental low-level jaw clenching can inhibit pain sensitivity, especially
      temporal summation. Low-level jaw clenching can modify pain sensitivity, most
      likely through the central nervous system. The findings suggest that potential
      harmful low-level jaw clenching or tooth contacting could continue despite
      painful symptoms, e.g., temporomandibular disorders.

PMID- 25757147
TI  - Assessment of sleep bruxism, orthodontic treatment need, orofacial dysfunctions
      and salivary biomarkers in asthmatic children.
AB  - OBJECTIVE: To evaluate the sleep bruxism, malocclusions, orofacial dysfunctions
      and salivary levels of cortisol and alpha-amylase in asthmatic children. DESIGN:
      108 7-9-yr-old children were selected from Policlinic Santa Teresinha Doutor
      Antonio Haddad Dib (asthmatics, n=53) and from public schools (controls, n=55),
      Piracicaba, SP, Brazil. Sleep bruxism diagnosis was confirmed by parental report
      of grinding sounds and the presence of shiny and polish facets on incisors and/or
      first permanent molars. The index of orthodontic treatment need was used for
      occlusion evaluation. Orofacial dysfunctions were evaluated using the nordic
      orofacial test-screening (NOT-S). Salivary cortisol and alpha-amylase were
      expressed as "awakening response" (AR), calculated as the difference between
      levels immediately after awakening and 30 min after waking, and "diurnal decline"
      (DD), calculated as the difference between levels at 30 min after waking and at
      bedtime. Data were analyzed using Shapiro-Wilk/Kolmogorov-Smirnov, Chi-square,
      unpaired t test/Mann-Whitney and paired t/Wilcoxon tests. RESULTS: Sleep bruxism
      was more prevalent in children with asthma than controls (47.2% vs. 27.3%,
      p<0.05). Asthmatics had higher scores of NOT-S total and interview (p<0.05).
      Dysfunctions on sensory function and chewing and swallowing were more frequent in
      asthmatics (p<0.05). Salivary cortisol AR on weekend was significantly higher for
      asthmatics (p<0.05). Salivary cortisol DD was significantly higher on weekday
      than weekend for controls (p<0.05). There were no significant differences in
      alpha-amylase values in and between groups. CONCLUSIONS: The presence of asthma
      in children was associated with sleep bruxism, negative perception of sensory,
      chewing and swallowing functions, and higher concentrations of salivary cortisol
      on weekend.

PMID- 25757148
TI  - Development of novel formulations containing Lysozyme and Lactoferrin and
      evaluation of antibacterial effects on Mutans Streptococci and Lactobacilli.
AB  - OBJECTIVE: The aim of this study was to determine the antibacterial effect of
      different formulations containing Lysozyme and Lactoferrin and drug delivery
      system as well as poloxamer 407 with the trade name of Pluronic F-127 and/or
      freeze dried liposome containing DOTAP [freeze dried Liposomal DOTAP] on
      Streptococcus sobrinus, Streptococcus mutans and Lactobacillus acidophilus in
      comparison with 0.2% chlorhexidine. MATERIALS AND METHODS: The antibacterial
      effect was assessed by determining the minimum inhibitory concentrations (MIC)
      for the study and control groups on Streptococcus sobrinus, Streptococcus mutans
      and Lactobacillus acidophilus. The amounts of biofilm formation accumulation of
      Mutans Streptococci for 24h on sterile hydroxyapatite discs after application of
      different formulations were evaluated. The different formulations studied were:
      (1) Sorensen's Buffer Solution, (2) a gel formulation containing only poloxamer
      407, (3) Lysozyme and Lactoferrin dissolved in Sorensen's Buffer Solution, (4)
      poloxamer 407 combined with the third formulation, (5) Freeze dried Liposomal
      DOTAP dissolved in Sorensen's Buffer Solution, (6) Freeze dried Liposomal DOTAP
      combined with poloxamer 407 dispersed in Sorensen's Buffer Solution, (7) Freeze
      dried Liposomal DOTAP combined with the third formulation, and (8) Lysozyme and
      Lactoferrin dissolved in Sorensen's Buffer Solution, which was then incorporated
      into poloxamer 407 and combined with Freeze dried Liposomal DOTAP. The positive
      and negative control groups were 0.2% chlorhexidine gel and empty hydroxyapatite
      discs, respectively. Statistical evaluation was carried out with Kruskal-Wallis
      and Dunn's multiple comparison tests. RESULTS: It was observed that the first,
      third and fifth groups did not have any antibacterial effects on the tested
      bacteria. The groups that contained poloxamer 407 had nearly identical
      antibacterial effects on Mutans Streptococci and L. acidophilus. These
      formulations also inhibited biofilm formation of the bacteria (p<0.05) more
      effectively. In the positive control group, there was no biofilm formation.
      CONCLUSIONS: Among the formulations containing poloxamer 407, the one containing
      Lysozyme and Lactoferrin exhibited the highest inhibitory effect on the tested
      bacteria. This novel formulation can be beneficial as an antibacterial agent for
      the prevention of dental caries and biofilm formation.

PMID- 25757149
TI  - A. actinomycetemcomitans profile and red complex bacterial species of an Afro
      Brazilian community: A comparative study.
AB  - PURPOSES: The primary aim of this cross-sectional study was to compare the levels
      of red complex bacteria between Afro-Brazilian and non Afro-Brazilian cohort. The
      secondary aim was to compare the distribution of both Aggregatibacter
      actinomycetemcomitans serotype b and its JP2 strains among participants who
      harboured this bacterial species. METHODS: A total of 84 individuals were
      included in this study: 42 Afro-descendants (mean age 35.9 +/- 13.1 years) and 42
      non-Afro-descendants (mean age 36.2 +/- 13.1 years) matched (1:1) by periodontal
      diagnosis, age and gender. All participants received clinical examinations of
      periodontal pocket depth, clinical attachment level, and plaque and gingival
      indices. Subgingival samples were taken for microbial analysis. First, genomic
      DNA (gDNA) was extracted and purified and the quantification of total number of
      bacterial cells, A. actinomycetemcomitans, Porphyromonas gingivalis, Tannerella
      forsythia and Treponema denticola was carried out by qPCR. Then, A.
      actinomycetemcomitans strains were classified according to serotype b and JP2
      profiles by conventional PCR. RESULTS: Clinically, mean PD, mean CAL and
      percentage of CAL >= 3 mm differed between groups (Student's t-test p<0.05). The
      levels of red complex bacteria between Afro-Brazilian and non-Afro-Brazilian
      populations were similar. The exception was verified to A. actinomycetemcomitans
      showing significantly higher levels among Afro-Brazilian descendants in
      comparison to non-Afro-Brazilian descendants. Afro-Brazilian descendants were
      clearly infected by more virulent serotype b and JP2 strains. CONCLUSIONS:
      Despite no statistically significant differences related to the red complex
      species, Afro-Brazilian descendants harboured higher levels of A.
      actinomycetemcomitans. Also, our findings confirm that Afro-descendant
      populations are preferably colonised by A. actinomycetemcomitans serotype b as
      well as JP2 strains.

PMID- 25757151
TI  - Oxidation state, a long-standing issue!

PMID- 25757150
TI  - The expression of periostin in dental pulp cells.
AB  - BACKGROUND AND OBJECTIVE: Dental pulp repair is a common process triggered by
      microbial and mechanical challenges. Matricellular modulators, such as periostin,
      are key for extracellular matrix stability and tissue healing. In the scope of
      the dental pulp, periostin expression has been reported during development and
      active dentinogenesis. However, the specific dental pulp cell population capable
      of expressing periostin in response to known regulators has not been clearly
      defined. Among the different relevant cell populations (i.e., stem cells,
      fibroblasts and pre-odontoblasts) potentially responsible for periostin
      expression in the dental pulp, this study aimed to determine which is the primary
      responder to periostin regulators. METHODS: Human dental pulp stem cells (DPSCs),
      human dental pulp fibroblasts (DPFs), and rat odontoblast-like cells (MDPC-23)
      were treated with different concentrations of TGF-beta1 or different regimens of
      biomechanical stimulation to evaluate periostin expression by qRT-PCR, Western
      blot and ELISA. Statistical analyses were performed by Student's t-test and ANOVA
      with Fisher's LSD post hoc tests (p <= 0.05). RESULTS: DPSC and MDPC-23 showed a
      statistically significant increase in periostin mRNA expression after exposure to
      TGF-beta1 for 48 h. TGF-beta1 also up-regulated periostin protein levels in DPSC.
      However, periostin significantly down-regulated protein expression in DPF.
      Different regimens of biomechanical stimulation showed different patterns in
      protein and mRNA periostin expression. CONCLUSIONS: Expression of periostin was
      identified in each of the analysed dental pulp cell lines, which can be regulated
      by TGF-beta1 and biomechanical stimulation. Overall, DPSCs are the most
      responsive cells to stimulation.

PMID- 25757152
TI  - Higher normal range of fasting plasma glucose still has a higher risk for
      metabolic syndrome: a combined cross-sectional and longitudinal study in elderly.
AB  - INTRODUCTION: It is well known that higher fasting plasma glucose (FPG) is
      associated with metabolic syndrome (MetS). This relationship still exists even
      the FPG is within the normal range. However, most of these studies did not
      exclude subjects who were on medications which would affect the results of the
      studies. At the same time, there is no longitudinal study done to validate this
      correlation, especially in elderly. In this study, the relationships between
      normal FPG and MetS were evaluated. METHOD: We randomly selected 57,517 subjects
      who were >= 60-years old from health screening centre. In the first part of
      study, subjects were enrolled in the cross-sectional study to find out the
      optimal cut-off value of FPG with higher chances to have MetS. In the second part
      of current study, subjects with MetS at baseline were excluded from the same
      study group, and performed a median 5.3-year longitudinal study. RESULTS: There
      were 18,287 subjects enrolled in this study. In the first part of study, the
      cross-sectional study, optimal cut-off values of FPG were determined by the ROC
      curve and the sensitivity for these cut-off values were 56.6% in men and 60.9% in
      women, respectively. The result showed that lower FPG is healthier than the
      higher (log-rank test, p < 0.001). During the follow-up period, 5039 subjects
      showed hazard ratios of 2.09 for men and 1.884 for women developing future MetS.
      CONCLUSION: Our study is the first longitudinal design in elderly and showed that
      older subjects with higher FPG proved to have higher risk of Mets even the FPG is
      still within its normal range.

PMID- 25757153
TI  - Regioselective hydration of terminal alkynes catalyzed by a neutral gold(I)
      complex [(IPr)AuCl] and one-pot synthesis of optically active secondary alcohols
      from terminal alkynes by the combination of [(IPr)AuCl] and Cp*RhCl[(R,R)
      TsDPEN].
AB  - A neutral gold(I) complex [(IPr)AuCl] (IPr = 1,3-bis(diisopropylphenyl)imidazol-2
      ylidene) was found to be a highly effective catalyst for the hydration of
      terminal alkynes, including aromatic alkynes and aliphatic alkynes. The desired
      methyl ketones were obtained in high yields with complete regioselectivities.
      Furthermore, a series of optically active secondary alcohols could be obtained in
      high yield with good to excellent enatioselectivities via one-pot sequential
      hydration/asymmetric transfer hydrogenation (ATH) from terminal alkynes by the
      combination of of [(IPr)AuCl] and Cp*RhCl[(R,R)-TsDPEN] (Cp* =
      pentamethylcyclopentadienyl, TsDPEN = N-(p-toluenesulfonyl)-1,2
      diphenylethylenediamine). Notably, this research exhibited the potential of the
      direct use of neutral gold(I) complexes instead of cationic ones as catalysts for
      the activation of multiple bonds for organic synthesis. 

PMID- 25757154
TI  - The N Terminus of alpha-Synuclein Forms Cu(II)-Bridged Oligomers.
AB  - The oligomerization of alpha-synuclein (alphaSyn) is one of the defining features
      of Parkinson's disease. Binding of divalent copper to the N terminus of alphaSyn
      has been implicated in both its function and dysfunction. Herein, the molecular
      details of the Cu(II) /alphaSyn binding interface have been revealed using a
      library of synthetic 56-residue alphaSyn peptides containing site-specific
      isotopic labels. Using electron paramagnetic resonance spectroscopy, alphaSyn is
      shown to coordinate Cu(II) with high affinity via two pH-dependent coordination
      modes between pH 6.5-8.5. Most remarkably, the data demonstrate that the dominant
      mode is associated with binding to oligomers (antiparallel dimers and/or cyclic
      trimers) in which Cu(II) ions occupy intermolecular bridging sites. The findings
      provide a molecular link between Cu(II) -bound alphaSyn and its associated
      quaternary oligomeric structure. 

PMID- 25757155
TI  - Investigating the order parameters of saturated lipid molecules under various
      curvature conditions on spherical supported lipid bilayers.
AB  - The conformations and motions of lipid molecules under different membrane
      curvatures have important implications for transmembrane protein function,
      binding events, and overall membrane organization. This work reports on the local
      order parameters of saturated lipid molecules, as measured by (13)C NMR
      relaxation, under several curvature conditions to probe structural changes as a
      function of lipid bilayer curvature. Different curvature conditions are created
      by depositing phosphatidylcholine membranes on spherical beads of various
      diameters. The findings reveal that the order parameters are not a continuous
      function of the membrane curvature. While small (30 nm) and large (110 nm)
      diameter bilayers exhibit similar order parameters, bilayers with curvatures of
      60-80 nm diameter show a consistently increased order parameter along the entire
      lipid molecule, indicating a higher packing density and lateral tension. Order
      parameters for curvatures between 60 and 80 nm also show molecular evidence for
      interdigitation. 

PMID- 25757156
TI  - A water-soluble ESIPT fluorescent probe with high quantum yield and red emission
      for ratiometric detection of inorganic and organic palladium.
AB  - A novel fluorescent probe with a high quantum yield (0.41), large Stokes shifts
      (255 nm), and red emission (635 nm) was designed to detect all typical oxidation
      states of palladium species (0, +2, +4) by palladium-mediated terminal propargyl
      ethers cleavage reaction in water solution without any organic media. The probe
      showed a high selectivity and excellent sensitivity for palladium species, with a
      detection as low as 57 nM (6.2 MUg L(-1)).

PMID- 25757157
TI  - Functional Significance of Nuclear alpha Spectrin.
AB  - Nonerythroid alpha spectrin (alphaIISp) interacts in the nucleus with an array of
      different proteins indicating its involvement in a number of diverse functions.
      However, the significance of these interactions and their functional importance
      has been a relatively unexplored area. The best documented role of nuclear
      alphaIISp is in DNA repair where it is critical for repair of DNA interstrand
      cross-links (ICLs), acting as a scaffold recruiting proteins to sites of damage
      in genomic and telomeric DNA. A deficiency in alphaIISp can importantly impact
      DNA ICL repair as is seen in cells from patients with the genetic disorder,
      Fanconi anemia (FA), where loss of alphaIISp leads to not only defects in repair
      of both genomic and telomeric DNA but also to telomere dysfunction and chromosome
      instability. This previously unexplored link between alphaIISp and telomere
      function is important in developing an understanding of maintenance of genomic
      stability after ICL damage. In FA cells, these defects in chromosome instability
      after ICL damage can be corrected when levels of alphaIISp are returned to normal
      by knocking down MU-calpain, a protease which cleaves alphaIISp. These studies
      suggest a new direction for correcting a number of the phenotypic defects in FA
      and could serve as a basis for therapeutic intervention. More in depth,
      examination of the interactions of alphaIISp with other proteins in the nucleus
      is of major importance in development of insights into the interacting key
      elements involved in the diverse processes occurring in the nucleus and the
      consequences loss of alphaIISp has on them.

PMID- 25757158
TI  - Role of Cu in Mo6S8 and Cu mixture cathodes for magnesium ion batteries.
AB  - The reversible capacity of Chevrel Mo6S8 cathode can be increased by the simple
      addition of the Cu metal to Mo6S8 electrodes. However, the exact reaction
      mechanism of the additional reversible capacity for the Mo6S8 and Cu mixture
      cathode has not been clearly understood yet. To clarify this unusual behavior, we
      synthesize a novel Cu nanoparticle/graphene composite for the preparation of the
      mixture electrode. We thoroughly investigate the electrochemical behaviors of the
      Mo6S8 and Cu mixture cathode with the relevant structural verifications during
      Mg(2+) insertion and extraction. The in situ formation of Cu(x)Mo6S8 is observed,
      indicating the spontaneous electrochemical insertion of Cu to the Mo6S8 host from
      the Cu nanoparticle/graphene composite. The reversible electrochemical
      replacement reaction of Cu in the Mo6S8 structure is clarified with the direct
      evidence for the solid state Cu deposition/dissolution at the surface of Mo6S8
      particles. Moreover, the Mo6S8 and Cu mixture cathode improves the rate
      capability compared to the pristine. We believe that our finding will contribute
      to understanding the origin of the additional capacity of the Mo6S8 cathode
      arising from Cu addition and improve the electrochemical performance of the Mo6S8
      cathode for rechargeable Mg batteries.

PMID- 25757159
TI  - Complexation of polyoxometalates with cyclodextrins.
AB  - Although complexation of hydrophilic guests inside the cavities of hydrophobic
      hosts is considered to be unlikely, we demonstrate herein the complexation
      between gamma- and beta-cyclodextrins (gamma- and beta-CDs) with an archetypal
      polyoxometalate (POM)--namely, the [PMo12O40](3-) trianion--which has led to the
      formation of two organic-inorganic hybrid 2:1 complexes, namely
      [La(H2O)9]{[PMo12O40]?[gamma-CD]2} (CD-POM-1) and [La(H2O)9] {[PMo12O40]?[beta
      CD]2} (CD-POM-2), in the solid state. The extent to which these complexes
      assemble in solution has been investigated by (i) (1)H, (13)C, and (31)P NMR
      spectroscopies and (ii) small- and wide-angle X-ray scattering, as well as (iii)
      mass spectrometry. Single-crystal X-ray diffraction reveals that both complexes
      have a sandwich-like structure, wherein one [PMo12O40](3-) trianion is
      encapsulated by the primary faces of two CD tori through intermolecular [C
      H...O?Mo] interactions. X-ray crystal superstructures of CD-POM-1 and CD-POM-2
      show also that both of these 2:1 complexes are lined up longitudinally in a one
      dimensional columnar fashion by means of [O-H...O] interactions. A beneficial
      nanoconfinement-induced stabilizing effect is supported by the observation of
      slow color changes for these supermolecules in aqueous solution phase.
      Electrochemical studies show that the redox properties of [PMo12O40](3-)
      trianions encapsulated by CDs in the complexes are largely preserved in solution.
      The supramolecular complementarity between the CDs and the [PMo12O40](3-)
      trianion provides yet another opportunity for the functionalization of POMs under
      mild conditions by using host-guest chemistry.

PMID- 25757161
TI  - Oxygen provision of the brain at various stages of operation in patients with
      chronic pulmonary artery thromboembolism.
AB  - The authors studied cerebral oxygen supply by means of cerebral oximetry in
      patients presenting with chronic pulmonary artery thromboembolism (PATE) at
      various stages of operation. The study was aimed at assessing cerebral oxygen
      supply while carrying out surgical treatment in patients with chronic PATE on the
      background of various methods of perfusion. Thromboendarterectomy (TEA) from the
      pulmonary artery with the use of circulatory arrest and craniocerebral
      hypothermia is accompanied by more pronounced impairment of oxygen supply of the
      brain with a decrease in the cerebral oxygenation indices by more than 30% from
      the baseline values. These alterations promote increased risk for the development
      of neurological complications in the early postoperative period. Using the
      technique of antegrade cerebral perfusion ensures a minimum decrease of cerebral
      oxygenation during TEA and contributes to a reduction of the risk for the
      development of neurological complications. 

PMID- 25757162
TI  - [Pulmonary artery thromboembolism on the background of hyperhomocysteinemia].
AB  - The article provides a detailed description of a clinical case report of acute
      massive pulmonary artery thromboembolism (PATE) in an elderly female patient. She
      was diagnosed with a carrier state of polymorphism of genes associated with
      impairment in the folate cycle MTHFR:677 - TT, MTRR:66 - AG and polymorphisms
      associated with disordered blood coagulation system F13 - GT; ITGB3:1565 - TC;
      SERPINE1 (PAI-1):675 - 4G4G. She was also found to have hyperhomocysteinemia -
      67.1 MUmol/l and hyperaggregation syndrome. Timely prescribed antithrombotic
      therapy and an agent containing in its base folic acid, vitamins B6 and B12 after
      surgical intervention in the scope of endovascular recanalization of pulmonary
      arteries and additional thromboembolic therapy resulted in a favourable outcome.

PMID- 25757160
TI  - Enhancement of the TCRzeta expression, polyclonal expansion, and activation of t
      cells from patients with acute myeloid leukemia after IL-2, IL-7, and IL-12
      induction.
AB  - Defective T cell receptor (TCR) signaling resulting in lower T cell function
      plays a crucial role in the pathogenesis of T cell immunodeficiency in leukemia.
      Previous studies have indicated that lower TCRzeta levels are a common
      characteristic of patients with leukemia, and upregulating TCRzeta could
      partially recover T cell function. In this study, we characterized the effect of
      the stimulating factor induction on the TCRzeta, Zap-70, and FcERIgamma levels,
      IFN-gamma secretion, and the distribution and clonal expansion of TCR Vbeta
      subfamilies in CD3(+) T cells sorted from peripheral blood from acute myeloid
      leukemia (AML) patients. The induction included single stimulating factor or a
      combination with different cytokines (IL-2, IL-7, IL-2+IL-7, IL-7+IL-12, CD3,
      CD3+CD28 antibody, CD3+CD28 antibody+IL-2, and CD3+CD28 antibody+IL-7) at 72 h.
      The results showed that increased TCRzeta and Zap-70 levels with deceased
      FcERIgamma in T cells after induction, and different responses to cytokine in T
      cell from different cases may indicate the heterogeneity of T cells and different
      immune statuses in different AML cases. Increased IFN-gamma levels in T cells
      from AML patients were detected after induction in the IL-12+IL-7, CD3+CD28+IL-2,
      and CD3+CD28+IL-7 groups. Moreover, the number of TCR Vbeta subfamily T cells
      expressed was increased; however, all of the TCR Vbeta subfamily T cells in the
      AML patients could not be completely recovered after induction. In conclusion,
      the cytotoxicity and activation function of T cells could be enhanced after
      induction by different stimuli accompanied by an increase in TCRzeta and Zap-70
      and recovery of the TCR Vbeta repertoire in AML patients. 

PMID- 25757163
TI  - [Oxidative carbonylation of vascular wall proteins in dynamics of experimental
      venous thrombosis].
AB  - The objects of the study were a total of 24 conventional sexually mature Wistar
      rats weighing 200-400 g. Thrombosis was modelled by means of ligation of the
      common iliac vein. Animals were withdrawn from the study on days 1, 3 and 5 after
      intervention. The materials for the study in each animal were homogenates of the
      vein portion below the site of ligation (thrombosed vein) and the portion of the
      symmetrical vessel (intact vein). Taken as controls were portions of the common
      iliac vein of intact animals matched by age, body weight, and keeping conditions.
      The level of spontaneous and induced in the Fenton reaction oxidative
      carbonylation of proteins was determined by means of carbonyl derivatives
      according to the R.L. Levine technique modified by E.E. Dubinina with optical
      registration of the formed dinitrophenylhydrazines at 356, 370, 430 and 530 nm.
      The reserve-and-adaptation potential was assessed by means of counting the ratio
      of the amount of carbonyl derivatives of proteins in spontaneous and induced
      oxidation. The obtained findings showed that experimental thrombosis is
      accompanied and followed by an increase in the content of carbonyl derivatives of
      proteins in the wall of thrombosed veins and, to a lesser degree, in that of
      intact veins. The maximal elevation of the parameters was registered during the
      first 24 hours of the development of pathology, demonstrating not only early but
      late markers of oxidative modification of proteins. Thrombosed veins on day 3
      were found to have a decrease in the content of carbonylated proteins to the
      level of the control values, which was associated with a maximal value of the
      reserve-adaptation potential. However, day five was marked by a secondary
      increase in carbonylation accompanied by certain exhaustion of the reserve
      adaptive potential. In intact veins, a decrease of the spontaneous oxidative
      modification level on day 3 was accompanied by a splash of induced carbonylation
      followed by stabilization of the parameters at the levels slightly exceeding the
      control values by day 5.

PMID- 25757164
TI  - [Criteria for efficacy of anticoagulant therapy in patients with thromboses of
      deep veins of lower limbs].
AB  - The authors analysed the results of a prospective study of dynamics of laboratory
      indices of plasma haemostasis on the background of anticoagulant therapy in a
      total of 60 patients (23 women and 37 men) presenting with idiopathic thromboses
      of deep veins of lower limbs in order to work out criteria for its efficacy and
      safety. Anticoagulant therapy was carried out using nonfractionated heparin
      according to the standard regimens. The patients' mean age amounted to 57.4+/
      13.6 years. Studying the system of haemostasis along with generally known
      standard laboratory indices (activated partial prothrombin time, D-dimer,
      fibrinogen, prothrombin level, INR, PTI) included one of the global coagulogical
      tests - a method of thrombodynamics whose main parameter was Vs (stationary clot
      growth rate). The results of anticoagulant therapy were assessed by dynamics of
      clinical symptomatology, the findings of ultrasonographic angioscanning, and by
      the dynamics of laboratory parameters of plasma haemostasis. The obtained
      findings demonstrated that anticoagulant therapy with nonfractionated heparin
      followed by switching to warfarin is an effective method of conservative
      treatment of patients with idiopathic thromboses, making it possible to attain
      laboratory confirmed hypocoagulation accompanied by both clinical and US
      controlled improvements. The results of the thrombodynamics assay by the dynamics
      of a decrease in the D-dimer level made it possible to statistically
      significantly single out a group with no effect of heparin (no effect of
      hypocoagulation) and high sensitivity in singling out groups of ineffective
      therapy with warfarin, which on the background of normo- or hypercoagulation is a
      marker of increased fibrinogenesis and, consequently, of high risk for the
      development of recurrent thrombosis in such patients. 

PMID- 25757166
TI  - [Review of materials of the 29th International Conference of the Russian
      Association of Angiologists and Vascular Surgeons].
AB  - The article reviews the materials of the 29th International Conference of the
      Russian Association of Angiologists and Vascular Surgeons "New trends and remote
      results of open endovascular interventions in treatment of vascular patients".
      Presented herein are the main results of scientific research in carotid surgery
      (carotid endarterectomy in the acute period of stroke, stenting), reconstructive,
      endovascular interventions in Leriche syndrome, pathology of lower-limb arteries,
      present-day technologies of treatment of aortic aneurysms (hybrid operations,
      endovascular prosthetic repair). 

PMID- 25757165
TI  - Use of polycaprolactone grafts for small-diameter blood vessels.
AB  - Current trends are toward actively developing approaches of tissue engineering,
      aimed at creating vascular grafts of small diameter. This is due to the existing
      in cardiovascular surgery demand for prostheses to be used in coronary artery
      bypass grafting. The present work was undertaken in order to assess possibilities
      of using smalldiameter vascular grafts made of biodegradable polymer
      polycaprolactone by means of electrospinning. The authors studied physico
      mechanical properties and structure of polycaprolactone grafts, as well as their
      thromboresistance and patency after implantation into the vascular bed of rats.
      The obtained results demonstrated optimal physicomechanical properties of the
      vascular grafts, their biocompatibility, endothelialisation of the internal
      surface, and infiltration of the graft's wall by cells with the formation of new
      tissue, accompanied and followed by the development of an extensive intimal layer
      in the zones of the anastomoses. Hence, the study showed possibilities of using
      polycaprolactone grafts as vascular prostheses, however requiring their further
      modification which would promote and contribute to a decrease in hyperplasia of
      connective tissue in the graft's lumen. 

PMID- 25757167
TI  - [Ischaemic lesions of cerebral after carotid stenting].
AB  - Carotid angioplasty with stenting is a reliable method of primary and secondary
      prevention of ischaemic stroke in patients with stenosing lesions of the internal
      carotid artery. However, carrying out such operations is sometimes associated
      with risk for the development of intraoperative impairments of cerebral
      circulation due to arterioarterial embolism in cerebral arteries, as well as
      vasospasm. Presented herein are the results of following up a total of 64
      patients with pronounced atherosclerotic lesions of internal carotid arteries
      (>70%) - "symptomatic" and "asymptomatic", undergoing carotid stenting. Acute
      foci of ischaemia in the brain after stenting according to the findings of
      diffusion-weighted magnetic resonance tomography were revealed in 40% of cases,
      and in only 6% of patients they manifested themselves by symptoms of acute
      cerebral circulatory impairment. We revealed a direct correlation between the
      number, size of infarctions in the brain, and the appearance of neurological
      symptomatology. Intraoperative monitoring of blood flow in the middle cerebral
      artery during stenting makes it possible to predict the appearance of acute foci
      of cerebral ischaemia, to specify the genesis of perioperative stroke, as well as
      to evaluate clinical significance of vasospasm and material microembolism. The
      obtained findings should concentrate neurologists' attention on active
      postoperative follow up of patients subjected to carotid angioplasty with
      stenting in order to perform adequate personified neuroprotective correction,
      including preventive one. 

PMID- 25757168
TI  - [Open operations or endovascular interventions in lesions of the first segment of
      the subclavian artery?].
AB  - MATERIAL AND METHODS: The study included a total of 110 patients presenting with
      stenoses of the first portion of the subclavian artery (SCA). Group One comprised
      55 (50%) patients subjected to carotid-subclavian bypass grafting. The degree of
      stenosis varied from 65 to 95% (p>0.05), occlusion of the SCA was found in 28
      (p<0.05) patients, permanent steal syndrome was observed in 39 (p>0.05) patients.
      Concomitant cardiac pathology was observed in 30 (55%) patients, with one (2%)
      patient having a history of stroke. Group Two was composed of 55 (50%) patients
      undergoing endovascular interventions. The degree of stenosis varied from 65 to
      95%, with eight patients having occlusion of the SCA. Permanent steal syndrome
      was observed in 36 patients. Accompanying cardiac pathology was noted in 28 (51%)
      patients, with eight (15%) patients having a history of stroke (p<0.05). RESULTS:
      In Group One, six months after surgery, of 41 cases thrombosis was revealed in 2
      patients. 2 years later, of 36 cases, thrombosis was detected in 7 patients.
      After 5 years, of 19 cases, thrombosis was revealed in 6. After more than 5
      years, of 11 cases thrombosis was revealed in 6. In Group Two 6 months after
      surgery, of 46 cases, the stent ceased to function in 8 patients. After 2 years,
      of 41 cases, 21 were found to have developed thrombosis. After 5 years - of 20
      cases, thrombosis was revealed in 16. Of 7 cases after more than 5 years the
      stent failed to function in 6. CONCLUSION: The operation of carotid-subclavian
      bypass grafting turned out more effective in the remote postoperative period.

PMID- 25757169
TI  - [Remote results of endovascular atherectomy with the SilverHawk device].
AB  - The authors studied the remote results of 27 endovascular catheter atherectomies
      performed in 25 patients. All patients had lesions of arteries of the
      femoropopliteal segment according to the TASC II classification. The duration of
      follow up varied from 6 to 34 months. Endovascular catheter atherectomy was
      carried out by means of the SilverHawk EV3 system with protection of the distal
      bed from embolism using Spider EV3. Our findings prove that catheter atherectomy
      with the SilverHawk system is most efficient it treatment of short stenotic
      lesions, lesions localizing in the zone of increased dynamic activity, multi
      level lesions of arteries of the femoropopliteal segment, as well as short
      lesions in patients suffering from diabetes mellitus. 

PMID- 25757170
TI  - [Two-stage treatment of a patient with type I aortic dissection: an open
      operation combined with endovascular prosthetic repair].
AB  - Presented herein are the results of clinical follow up of a patient with type I
      aortic dissection, subjected to two-stage treatment: the first stage consisted in
      prosthetic repair of the ascending portion of the aorta and aortic arch, the
      second stage being endovascular prosthetic repair of the thoracic portion of the
      aorta with a stent graft. The ostium of the left subclavian artery entrapped into
      the zone of implantation of the stent graft was occluded by means of the
      "Amplatzer" device. 

PMID- 25757171
TI  - [Possibilities and results of using clopidogrel (Listab) in comprehensive
      treatment of patients with crural deep veins thrombosis].
AB  - The authors carried out a prospective non-randomized controlled study including
      patients undergoing conservative treatment for acute thrombosis of crural deep
      veins with a stable course of the disease. A total of 60 patients discharged from
      hospital for further outpatient follow up and treatment were subdivided into two
      groups: Group I (study group, "Listab" group) composed of 35 patients who
      immediately began taking prescribed clopidogrel ("Listab") at a dose of 75 mg a
      day, and Group II (first control group, "VKA" group) comprising 25 patients
      receiving vitamin K antagonists (VKA) at various doses according to the generally
      accepted recommendations. We retrospectively formed Group III consisting of 21
      patients (second control group, "ASA or VKA" group) who despite initial
      prescription of VKA either received them interruptedly and only for a short time
      after discharge from hospital or took preparations of acetylsalicylic acid (ASA)
      alone. The cumulative index of freedom from negative clinical outcomes after 12
      months of follow up in the "Listab" group amounted to 0.9143, in the "VKA" group
      to 0.9600, and in the "ASA or VKA" group to 0.7619. The cumulative index of
      freedom from negative clinical and/or ultrasound outcomes after 12 months of
      follow up amounted to 0.8571, 0.8400, and 0.6190, respectively. In the "Listab"
      group the relative incidence of adverse events while taking the drug as
      calculated per 100 patient-months amounted to 1.79 and in the "VKA" group to
      2.95. Administration of Listab was associated with the best patient compliance as
      compared to other drugs (VKA and ASA). The proportion of patients reporting
      regular taking of the drug in the "Listab" group amounted to 91.4%. A conclusion
      was drawn that in patients with crural deep vein thrombosis with a stable course
      of the acute period of the disease Listab may be used effectively and safely in
      comprehensive ambulatory treatment of patients having low adherence to taking VKA
      and to regular laboratory monitoring of the coagulation level (or if such
      monitoring is impossible), as well as in cases of high risk of haemorrhage while
      taking VKA. The final determination of the possibility of using clopidogrel
      containing drugs and their place in treatment of the pathology concerned requires
      larger clinical trials. 

PMID- 25757172
TI  - [Experience with clinical administration of new drug Thrombovasim(r) in vascular
      surgery].
AB  - Recent years have witnessed an increased worldwide interest in medical use of
      unique naturally occurring enzymes - subtilisins possessing pronounced
      fibrinolytic and anti-inflammatory properties. The article deals with experience
      in clinical administration in vascular surgery of new therapeutic agent
      Thrombovasim(r) containing pegylated subtilisin as an active substance.
      Thrombovasim(r) has a favourable profile of safety, good tolerance and causes no
      severe haemorrhagic complications. The pharmacological action of Thrombovasim(r)
      consists in combination of the targeted effect on the fibrin carcass of the
      thrombus without participation of the own system of haemostasis and anti
      inflammatory effect. In the Russian Federation Thrombovasim(r) has been used for
      6 years predominantly in vascular pathology of lower limbs accompanied by the
      development of chronic venous insufficiency. 

PMID- 25757173
TI  - [Endovascular laser obliteration in treatment of patients with varicose veins
      with trophic disorders].
AB  - The authors studied efficacy and safety of endovasal laser obliteration (EVLO) in
      treatment for varicose veins in patients with trophic disorders, carrying out
      comparative analysis of the outcomes of treatment of 95 patients subjected to
      EVLO (Study Group) or combined phlebectomy (Control Group). It was shown that
      EVLO is accompanied by less traumatic lesion of tissues during interventions,
      thus leading to more rapid relief of oedemas of lower limbs and reduction of
      trophic skin disorders. In patients with open trophic ulcers with an area of more
      than 10 cm2 healing occurred averagely one month faster than in those after
      phlebectomy. Hence, EVLO may be recommended as a preferable technique in
      treatment of varicose veins in patients with trophic disorders. However, if the
      diameter of the venous trunk exceeds 1 cm there is a probability of its
      recanalization even in the remote period after the intervention. 

PMID- 25757174
TI  - [Review of materials XVII World Congress of the International Union of
      Phlebologists (Boston, Massachusetts, USA, 2013)].
AB  - The article contains a review of the materials presented at the XVII World
      Congress of the International Union of Phlebology held in Boston in September
      2013. Analysed herein are the opinions and experience of phlebologists from
      various countries. The contributors discussed various aspects of using foam
      sclerotherapy and thermal methods of ablation, briefly representing the results
      of studies concerning thromboses and embolisms, anatomy of veins and methods of
      ultrasound examination, epidemiology of chronic venous diseases (CVDs), relapses
      of varicose veins, pharmacotherapy of CVDs, etc. 

PMID- 25757175
TI  - [Experience in diagnosis and treatment of combined lesions of the extra- and
      intracranial portions of the internal carotid artery].
AB  - The treatment policy concerning patients with lesions of the extra- and
      intracranial portions of carotid arteries is currently uncertain. The authors
      share herein their experience in diagnosis and treatment of 5 patients presenting
      with lesions of the extracranial portions of the internal carotid artery
      (stenosis/occlusion/pathological tortuosity) combined with arterial aneurysms and
      arteriovenous malformations of the brain. Of these, two patients were operated
      on: the first one was primarily subjected to clipping of the cerebral aneurysm
      then after several months underwent a reconstructive vascular operation on the
      ipsilateral side (resection of the internal carotid artery with its
      readdressing). The second patient with subtotal stenosis of the internal carotid
      artery who initially underwent clipping of the ipsilateral asymptomatic aneurysm
      of the middle cerebral artery developed occlusion of the internal carotid artery
      by the second stage of treatment and was not subjected to vascular operation.
      There were no is-chaemic cerebral complications or lethal outcomes in the
      operated patients in peri- and post-operative periods at all stages of treatment.

PMID- 25757176
TI  - [Aorta-associated complications after prosthetic repair of the aortic valve].
AB  - The authors analyzed dependence between the presence of preoperative predictors
      of aorta-associated complications and risk for the development of these
      complications in the remote period after prosthetic repair of the aortic valve.
      The study included a total of 231 patients subjected to aortic valve prosthetic
      repair with no additional intervention on the root and ascending portion of the
      aorta. The follow up duration varied from 12 to 62 months. As predictors of the
      development of aorta-associated complications we examined such factors as the
      bicuspid structure of the aortic valve, dilatation of the aortic ascending
      portion relative to the upper border of the individually calculated norm,
      disordered configuration of the complex "aortic root - ascending portion of the
      aorta", resistant arterial hypertension, diabetes mellitus. Depending on the
      number of predictors for the development of aorta-associated complications the
      patients were subdivided into 2 groups: Group One consisting of 105 patients with
      two and more predictors of the development of aorta-associated complications, and
      Group Two comprising 126 patients with not more than one predictor of the
      development of aorta-associated complications. It was determined that in the
      first group of patients the total number of aorta-associated complications in the
      remote period after prosthetic repair of the aortic valve amounted to 25.7% (27
      of 105 patients). The total number of aorta-associated complications in the
      second group amounted to 1.6% (2 of 126 patients). All detected aorta-associated
      complications were divided into "critical" and "noncritical". The critical
      complications were those the detection of which required performing a second
      operation in the patient: formation of an ascending aortic aneurysm and type A
      aortic dissection. To the "noncritical" aorta-associated complications belonged
      dilatation of the ascending portion of the aorta progressing at a rate of 2
      mm/year. Resulting from the performed study it was determined that each specific
      of the examined predictors exerted no influence on the risk for the development
      of aorta-associated complications in the remote period after prosthetic repair of
      the aortic valve (p>0.05). Any combination of two and more predictors in one
      patient considerably increased the risk for the development of complications
      (p<0.001). A conclusion was made that revealing two and more predictors of the
      development of aorta-associated complications in one patient it is appropriate to
      perform a simultaneous operation of prosthetic repair of the aortic valve and the
      ascending aortic portion. 

PMID- 25757177
TI  - [Remote results of reimplantation of the aortic valve in patients with ascending
      aortic aneurysm accompanied by aortic insufficiency].
AB  - Valve-sparing operations on the aorta has recently been gaining ever increasing
      popularity due to more detailed study of physiology of the aortic root, as well
      as promising mid- and long-term results. The world practice uses various
      techniques making it possible to remove both ascending aortic aneurysm and aortic
      valve insufficiency. The authors herein describe and analyse their experience in
      performing reimplantation of the aortic valve in patients with ascending aortic
      aneurysm and concomitant aortic insufficiency. Specialists of the clinic of the
      Novosibirsk Scientific Research Institute for Circulatory Pathology during the
      period from 2003 to 2013 performed a total of 77 operations of reimplantation of
      the aortic valve in patients with ascending aortic aneurysm and pronounced aortic
      valve insufficiency. The majority of patients were men (57 males and 20 females),
      mean age 53.1+/-12.2 years (range 21-72). 80% of cases had NYHA functional class
      II-III circulatory insufficiency (degree 2.3+/-0.7). Preoperative examination
      revealed in the majority of patients (97.4%) moderate-to-severe aortic valve
      insufficiency and ascending aortic aneurysm. All patients underwent
      reimplantation of the aortic valve. The duration of artificial circulation
      amounted to 202.4+/-33 minutes, with the average time of aortic occlusion being
      164+/-28 min. Accompanying procedures (annuloplasty of the mitral valve and/or
      coronary aortic bypass grafting) were performed in 12 (15.6%) cases. Additional
      plasty of valvular cusps was carried out in 9 (11.7%) patients, with
      rethoracotomy required in 5 (6.4%) cases due to haemorrhage. The average period
      of follow up amounted to 53.3+/-8.5 (3-115) months. During this time total
      survival amounted to 91%, with freedom from aortic valve prosthetic repair
      equalling 93%. The obtained findings suggest that aortic valve reimplantation
      into the prosthesis is a safe intervention and associated with a comparatively
      low level of operative lethality. Moderate aortic insufficiency at discharge is a
      predicting factor for repeat surgical intervention, i.e. prosthetic repair of the
      aortic valve. No association between the preoperative degree of aortic
      insufficiency, root diameter and durability of the reimplanted valve was
      revealed. 

PMID- 25757178
TI  - [Policy of using the right internal thoracic artery "in situ" for coronary artery
      bypass grafting].
AB  - The authors analysed the outcomes in a total of 73 patients subjected to coronary
      artery bypass grafting with the use of the "in situ" the right internal thoracic
      artery. Of these, 14 patients endured bypass grafting with assessment of the
      conformity of the length of the "in situ" right ITA as a conduit for the distal
      third of the right coronary artery (RCA). 16 patients underwent grafting of the
      RITA "in situ" with the RCA by passing through the pleural cavity. The remaining
      43 patients were subjected to bilateral mammary composite bypass grafting using
      the radial artery (RA). A total of 22 segments of the RA were subjected to a
      comparative morphometric examination depending on the method of exposure. We
      additionally analysed 56 cases of utilizing the RA with the use of the
      pharmacological protocol of preventing spasm. The results were regarded
      statistically significant if p<0.05. We used the non-parametric criterion of Mann
      Whitney. The obtained results showed that the right ITA "in situ" may be used for
      bypass grafting of the RCA system, excluding the risk of graft tension, if the
      perpendicular from the 6th intercostal space crosses the sharp edge of the heart
      1.5-2 cm distal to the medial point, with the minimum number of complications
      after 1.5+/-0.3 years (7.1%). When the above-mentioned perpendicular is located
      proximal to the middle point of the sharp edge of the heart it is possible to use
      the right ITA "in situ" for the RCA system thanks to passing the conduit through
      the right pleural cavity under the anterior segment of the upper lobe and the
      medial segment of the middle lobe of the right lung with no complications after 1
      year. The method of composite bypass grafting by means of the proximal segment of
      the right ITA "in situ" and the RA makes it possible to effectively revascularize
      any portions of the coronary bed (latency 94.7% after 3.0+/-0.8 years), to avoid
      manipulations on the aorta, and to save the bed of the right ITA in the middle
      and distal third of the sternum with no postoperative complications. It was
      revealed that in the conditions of decreased osmotic pressure the increase in the
      thickness of the vascular wall is more pronounced in the skeletonized segments of
      the RA (1.38+/-0.05 mm) as compared with the segments surrounded by connective
      and fatty tissue (1.09+/-0.04 mm). The pharmacological protocol for prevention of
      radial artery spasm used in 56 patients resulted in a small number of
      complications observed after 3.0+/-0.8 years (myocardial infarctions - 1.75%,
      angina pectoris relapse - 7%). Hence, the developed methods of using the right
      ITA "in situ" widen possibilities of bilateral mammary bypass grafting, excluding
      the existing problems of routine use of the both ITAs "in situ". 

PMID- 25757179
TI  - Mechanisms and prevention of anterior spinal artery syndrome following abdominal
      aortic surgery.
AB  - Paraplegia or paraparesis occurring as a complication of thoracic or
      thoracoabdominal aortic aneurysm repair is a well known phenomenon, but the vast
      majority of elective abdominal aortic aneurysm repairs are performed without
      serious neurological complications. Nevertheless, there have been many reported
      cases of spinal cord ischaemia following the elective repair of abdominal aortic
      aneurysms (AAA); giving rise to paraplegia, sphincter incontinence and, often,
      dissociated sensory loss. According to the classification made by Gloviczki et
      al. (1991), this presentation is classified as type II spinal cord ischaemia,
      more commonly referred to as anterior spinal artery syndrome (ASAS). It is the
      most common neurological complication occurring following abdominal aortic
      surgery with an incidence of 0.1-0.2%. Several aetiological factors, including
      intra-operative hypotension, embolisation and prolonged aortic crossclamping,
      have been suggested to cause anterior spinal artery syndrome, but the principal
      cause has almost always been identified as an alteration in the blood supply to
      the spinal cord. A review of the literature on the anatomy of the vascular supply
      of the spinal cord highlights the significance of the anterior spinal artery as
      well as placing additional emphasis on the great radicular artery of Adamkiewicz
      (arteria radicularis magna) and the pelvic collateral circulation. Although there
      have been reported cases of spontaneous recovery, complete recovery is uncommon
      and awareness and prevention remains the mainstay of treatment. However, being so
      tragically unpredictable and random, spinal cord ischaemia after abdominal aortic
      operations appears to be an unpreventable event. 

PMID- 25757180
TI  - [Five-year results of surgical management of patients with chronic post-embolic
      pulmonary hypertension].
AB  - Over the period from 2004 to 2013, a total of 146 patients presenting with
      chronic post-embolic pulmonary hypertension (CPEPH) underwent the operation of
      pulmonary thromboendarterectomy (TEE) at the Centre for Surgery of the Aorta,
      Coronary and Peripheral Arteries. The operation was carried out according to the
      conventional technique with the use of hypothermia and circulatory arrest. The
      dynamics of the clinical and functional state was assessed by analysing the
      following parameters: 6-minute walk test, mean pulmonary artery pressure, and
      resistance of lesser circulation vessels (according to the data of
      catheterization of the right parts of the heart), as well as the diameter of the
      pulmonary artery trunk (by data of MSCT angiography of the pulmonary artery). The
      distance of the 6-minute walk was indicative of the corresponding functional
      class of chronic heart failure according to the NYHA classification. The obtained
      results showed that pulmonary TEE eliminates the main cause of pulmonary
      hypertension - thrombotic obstruction of pulmonary arteries, thus leading to
      normalization of the lesser circulation, a decrease in the load on the right
      ventricle and, consequently, to considerable improvement of the functional state
      of patients. Performing the operation of TEE from PA branches leads to improved
      clinical and functional condition of patients with CPEPH both at the hospital
      stage and further in the remote period after surgery, which is confirmed by a
      more than 2.5-fold increase of the 6-minute walk distance and a decrease of CHF
      functional class (by NYHA). A decrease of vascular resistance of the lesser
      circulation from 539.66+/-120.59 din*s*cm(-5) before surgery to 101.39+/-89.20
      din*s*cm(-5) in the remote period is indicative of remodelling of the right
      ventricle and distal arterioles of the lesser circulation. A decrease of the PA
      trunk diameter from 35.10+/-5.25 mm before the operation to 30.30+/-8.65 mm in
      the remote period is suggestive of structural rearrangement of the pulmonary
      arterial bed with a tendency towards normalization and of efficacy of surgical
      treatment performed. 

PMID- 25757181
TI  - [Combined treatment of arteriovenous malformations of the head and neck].
AB  - An arteriovenous malformation (AVM) is a vascular developmental abnormality
      conditioned by impaired embryonic morphogenesis and characterized by the
      development of an abnormal connection between arteries and veins. More than 50%
      of the total number of patients suffering from this pathology are those having
      the pathological foci localizing in the area of the head and neck. At present, a
      combined method is both a generally accepted and the most radical one used for
      treatment for AVM. However, in the majority of cases, excision of the
      malformation leaves an extensive and complicated defect of tissues, whose direct
      closure leads to coarse cicatricious deformities. Over the period from 2004 to
      2012, we followed up a total of 37 patients presenting with arteriovenous
      malformations of the head and neck. At admission the patients underwent
      preoperative examination including clinical tests, ultrasound duplex scanning,
      arteriography, MRT, and computed tomography. 24-72 hours prior to the operative
      intervention the patients were subjected to embolisation of the main vessels
      supplying the vascular malformation. Excision of the AVM was in 8 cases followed
      by primary closure of the postoperative wound, in 17 patients the defect was
      closed by transposition of the axial flaps, and 12 subjects underwent free
      transplantation of composite complexes of tissues. Relapse of the disease was
      revealed in 17 patients. In the majority of cases, relapses developed during the
      first year after the operative intervention (10 cases). The control of the
      disease's course was obtained in 20 patients. In 8 of the 12 patients with free
      transplantation of flaps we managed to obtain long-term control over the
      disease's course (more than 5 years). Hence, free microsurgical transplantation
      of compound complexes of tissues may be considered as a method of choice for
      closing the defect after excising an AVM in the area of the head and neck.
      Replacement of the defect with a well-vascularized tissue complex considerably
      improves regional haemodynamics, decreases tissue ischaemia, and is capable of
      providing longterm control over the disease's course. 

PMID- 25757182
TI  - [Experience with implantation of a fenestrated endoprosthesis to a patient with a
      juxtarenal aortic aneurysm].
AB  - In patients with a juxtarenal abdominal aortic aneurysm the unaltered segment is
      frequently insufficient to secure adequate proximal fixation of the stent graft
      or is entirely absent, thus making it problematic to exclude the aneurysm from
      the blood flow by means of classic endoprosthetic repair. For this reason, in
      order to preserve the blood flow through visceral and renal arteries fenestrated
      endoprostheses are used as alternative minimally invasive treatment policy.
      Described herein is the first in the Russian Federation clinical case of using a
      fenestrated endovascular graft for treatment of a juxtarenal aortic aneurysm. Our
      patient had high surgical risk due to severe concomitant pathology and was
      therefore subjected to implantation of a fenestrated endoprosthesis with the
      preservation of the blood flow through the superior mesenteric artery and both
      renal arteries. The operation was successful with the complete exclusion of the
      aneurysm from the blood flow. The first and subsequent controls in the
      postoperative period showed an adequate position of the endoprosthesis and normal
      blood flow through the visceral branches. 

PMID- 25757183
TI  - [Surgical treatment of a patient with giant false aneurysm of xenopericardial
      conduit of the ascending aorta].
AB  - The article deals with a clinical case report concerning successful secondary
      surgical intervention for a giant pseudoaneurysm of the xenopericardial conduit
      of the ascending aorta in a patient with type A chronic aortic dissection, with a
      history previously endured prosthetic repair of the ascending aorta and aortic
      valve for acute dissection. The patient underwent was subjected to repeat
      prosthetic repair of the aortic valve and ascending aorta according to the
      Cabrol's technique. The postoperative period was uneventful. The function of the
      aortic valve prosthesis after surgery was satisfactory. The control multispiral
      computed tomography showed that reconstruction zone was without deformities, with
      the ostia of coronary arteries patent. On day 15 postoperatively the patient was
      discharged from hospital to undergo rehabilitation with recommendations
      concerning the subsequent stage of surgical treatment. The conclusion was drawn
      that despite life-threatening disease and an extensive scope of reconstruction
      correctly chosen surgical policy makes it possible to adequately carry out the
      necessary operation with a good outcome. 

PMID- 25757184
TI  - [Paradoxical embolism: clinical situation and approaches to treatment].
AB  - The authors describe two clinical cases of paradoxical embolism of greater
      circulation vessels in patients with thrombosis of deep veins of the lower
      extremities and patent foramen ovale, also discussing different variants of
      clinical course of paradoxical embolism, as well as approaches to treatment and
      prevention. 

PMID- 25757185
TI  - Mesiodistal inclination of the unerupted second premolar in the mandible of
      Japanese orthodontic patients with incisor agenesis.
AB  - OBJECTIVE: To elucidate the mesiodistal inclination of the unerupted mandibular
      second premolar (MnP2) in cases of mandibular incisor (MnIc) agenesis and
      unilateral MnP2 agenesis. MATERIALS AND METHODS: Twenty-two cases of unilateral
      MnP2 agenesis (MnP2 agenesis group) and a control group (control group A) of 22
      cases without permanent tooth agenesis excluding third molars were selected.
      Thirty-six cases of MnIc agenesis (MnIc agenesis group) and another control group
      (control group B) of 36 subjects were also selected. Mesiodistal inclination of
      the unerupted MnP2 on the panoramic X-rays was measured according to the distal
      angle and premolar-molar angle using the methods of Shalish et al. and Baccetti
      et al., respectively. Differences in mean values of the angular measurements
      between agenesis groups and corresponding controls were investigated (unpaired t
      test). RESULTS: In the MnP2 agenesis group, the mean distal angle decreased 12.3
      degrees  and the mean premolar-molar angle increased 13.3 degrees  for the MnP2
      compared with control group A (both P < .001). In the MnIc agenesis group, no
      significant differences in the means of those angles for the MnP2 were found when
      compared with control group B. CONCLUSION: In Japanese orthodontic patients,
      there is a relationship between unilateral MnP2 agenesis and the mesiodistal
      angulation of the unerupted MnP2. However, no significant relationship was
      observed between MnIc agenesis (which relationship is often seen in Asian
      populations) and the position of the unerupted MnP2. These results suggest that
      different genetic factors are involved in MnP2 agenesis and MnIc agenesis.

PMID- 25757186
TI  - DNAzyme hybridization, cleavage, degradation, and sensing in undiluted human
      blood serum.
AB  - RNA-cleaving DNAzymes provide a unique platform for developing biosensors.
      However, a majority of the work has been performed in clean buffer solutions,
      while the activity of some important DNAzymes in biological sample matrices is
      still under debate. Two RNA-cleaving DNAzymes (17E and 10-23) are the most widely
      used. In this work, we carefully studied a few key aspects of the 17E DNAzyme in
      human blood serum, including hybridization, cleavage activity, and degradation
      kinetics. Since direct fluorescence monitoring is difficult due to the opacity of
      serum, denaturing and nondenaturing gel electrophoresis were combined for
      studying the interaction between serum proteins and DNAzymes. The 17E DNAzyme
      retains its activity in 90% human blood serum with a cleavage rate of 0.04 min(
      1), which is similar to that in the PBS buffer (0.06 min(-1)) with a similar
      ionic strength. The activity in serum can be accelerated to 0.3 min(-1) with an
      additional 10 mM Ca(2+). As compared to 17E, the 10-23 DNAzyme produces
      negligible cleavage in serum. Degradation of both the substrate and the DNAzyme
      strand is very slow in serum, especially at room temperature. Degradation occurs
      mainly at the fluorophore label (linked to DNA via an amide bond) instead of the
      DNA phosphodiester bonds. Serum proteins can bind more tightly to the 17E DNAzyme
      complex than to the single-stranded substrate or enzyme. The 17E DNAzyme
      hybridizes extremely fast in serum. With this understanding, the detection of DNA
      using the 17E DNAzyme is demonstrated in serum. 

PMID- 25757187
TI  - Pathway for insertion of amphiphilic nanoparticles into defect-free lipid
      bilayers from atomistic molecular dynamics simulations.
AB  - Gold nanoparticles (NPs) have been increasingly used in biological applications
      that involve potential contact with cellular membranes. As a result, it is
      essential to gain a physical understanding of NP-membrane interactions to guide
      the design of next-generation bioactive nanoparticles. In previous work, we
      showed that charged, amphiphilic NPs can fuse with lipid bilayers after contact
      between protruding solvent-exposed lipid tails and the NP monolayer. Fusion was
      only observed at the high-curvature edges of large bilayer defects, but not in
      low-curvature regions where protrusions are rarely observed. Here, we use
      atomistic molecular dynamics simulations to show that the same NPs can also fuse
      with low-curvature bilayers in the absence of defects if NP-protrusion contact
      occurs, generalizing the results of our previous work. Insertion proceeds without
      applying biasing forces to the NP, driven by the hydrophobic effect, and involves
      the transient generation of bilayer curvature. We further find that NPs with long
      hydrophobic ligands can insert a single ligand into the bilayer core in a manner
      similar to the binding of peripheral proteins. Such anchoring may precede
      insertion, revealing potential methods for engineering NP monolayers to enhance
      NP-bilayer fusion in systems with a low likelihood of lipid tail protrusions.
      These results reveal new pathways for NP-bilayer fusion and provide fundamental
      insight into behavior at the nano-bio interface. 

PMID- 25757188
TI  - Equivalent Lung Dose and Systemic Exposure of Budesonide/Formoterol Combination
      via Easyhaler and Turbuhaler.
AB  - BACKGROUND: Easyhaler((r)) device-metered dry powder inhaler containing
      budesonide and formoterol fumarate dihydrate (hereafter formoterol) for the
      treatment of asthma and chronic obstructive pulmonary disease has been developed.
      The current approvals of the product in Europe were based on several
      pharmacokinetic (PK) bioequivalence (BE) studies, and in vitro-in vivo
      correlation (IVIVC) modeling. METHODS: Four PK studies were performed to compare
      the lung deposition and total systemic exposure of budesonide and formoterol
      after administration of budesonide/formoterol Easyhaler and the reference
      product, Symbicort Turbuhaler. The products were administered concomitantly with
      oral charcoal (lung deposition) and in two of the studies also without charcoal
      (total systemic exposure). Demonstration of BE for lung deposition (surrogate
      marker for efficacy) and non-inferiority for systemic exposure (surrogate marker
      for safety) were considered a proof of therapeutic equivalence. In addition,
      IVIVC models were constructed to predict study outcomes with different reference
      product fine particle doses (FPDs). RESULTS: In the first pivotal study, the
      exposure and lung dose via Easyhaler were higher compared to the reference
      product (mean comparison estimates between 1.07 and 1.28) as the FPDs of the
      reference product batch were low. In the following studies, reference product
      batches with higher FPDs were utilized. In the second pivotal study, non
      inferiority of Easyhaler compared to Turbuhaler was shown in safety and BE in
      efficacy for all other parameters except the formoterol AUCt. In the fourth study
      where two reference batches were compared to each other and Easyhaler,
      budesonide/formoterol Easyhaler was bioequivalent with one reference batch but
      not with the other having the highest FPDs amongst the 28 reference batches
      studied. In the IVIVC based study outcome predictions, the test product was
      bioequivalent with great proportion of the reference batches. For the test
      product and the median FPD reference product BE was predicted. CONCLUSIONS:
      Equivalence regarding both safety and efficacy between budesonide/formoterol
      Easyhaler and Symbicort Turbuhaler was shown based on totality of evidence from
      the PK studies and IVIVC analyses, and therefore, therapeutic equivalence between
      the products can be concluded. The results of the PK studies are likely dependent
      on the variability of FPDs of the reference product batches.

PMID- 25757189
TI  - Alendronate inhalation ameliorates elastase-induced pulmonary emphysema in mice
      by induction of apoptosis of alveolar macrophages.
AB  - Alveolar macrophages play a crucial role in the pathogenesis of emphysema, for
      which there is currently no effective treatment. Bisphosphonates are widely used
      to treat osteoclast-mediated bone diseases. Here we show that delivery of the
      nitrogen-containing bisphosphonate alendronate via aerosol inhalation ameliorates
      elastase-induced emphysema in mice. Inhaled, but not orally ingested, alendronate
      inhibits airspace enlargement after elastase instillation, and induces apoptosis
      of macrophages in bronchoalveolar fluid via caspase-3- and mevalonate-dependent
      pathways. Cytometric analysis indicates that the F4/80(+)CD11b(high)CD11c(mild)
      population characterizing inflammatory macrophages, and the
      F4/80(+)CD11b(mild)CD11c(high) population defining resident alveolar macrophages
      take up substantial amounts of the bisphosphonate imaging agent OsteoSense680
      after aerosol inhalation. We further show that alendronate inhibits macrophage
      migratory and phagocytotic activities and blunts the inflammatory response of
      alveolar macrophages by inhibiting nuclear factor-kappaB signalling. Given that
      the alendronate inhalation effectively induces apoptosis in both recruited and
      resident alveolar macrophages, we suggest this strategy may have therapeutic
      potential for the treatment of emphysema. 

PMID- 25757191
TI  - Synthesis of cyclic polyesters: effects of alkoxy side chains in
      salicylaldiminato tin(II) complexes.
AB  - A new class of salicylaldiminato tin(II) catalysts having different alkoxy side
      chains has been developed. The ligands were modified to have different lengths
      and flexibilities such as -(CH2)2- (2a), -(CH2)3- (2b), -(ortho-C6H4)CH2- (2c)
      and -(CH2)2-O-(CH2)2- (2d). Complexes 2a, b were characterized
      crystallographically revealing a more constrained environment around the metal in
      complex 2a. These catalysts are active for the solvent-free polymerization of L
      lactide and epsilon-caprolactone. Complex 2a having a shorter side chain was
      shown to better promote intramolecular transesterification affording cyclic
      polylactides and cyclic poly(epsilon-caprolactone). Complexes 2b and 2d having
      longer side chains produced cyclic poly(epsilon-caprolactone) as a major product
      but failed to give cyclic polylactides.

PMID- 25757192
TI  - Single-molecule FRET and crosslinking studies in structural biology enabled by
      noncanonical amino acids.
AB  - Contemporary structural biology research promises more than just static snap
      shots of molecular machineries. This goal is not just facilitated by combining
      different structural biology techniques, but also by new tools from the field of
      protein and genetic engineering, as well as from chemistry. Genetic encoding of
      noncanonical amino acids (ncAAs) through codon-suppression technology provides an
      excellent opportunity to probe biomolecules using different structural biology
      methods. In this article, we review the applications of ncAA incorporation into
      proteins for determining structural information through various techniques with
      the main focus on crosslinking mass spectrometry and single-molecule FRET-based
      techniques. Furthermore, advances and limitations of the incorporation of
      multiple ncAAs are discussed, with respect to design of an ideal host organism
      for modern and integrative structural biology research. 

PMID- 25757193
TI  - Comparative insight into nucleotide excision repair components of Plasmodium
      falciparum.
AB  - Nucleotide excision repair (NER) is one of the DNA repair pathways crucial for
      maintenance of genome integrity and deals with repair of DNA damages arising due
      to exogenous and endogenous factors. The multi-protein transcription initiation
      factor TFIIH plays a critical role in NER and transcription and is highly
      conserved throughout evolution. The malaria parasite Plasmodium falciparum has
      been a challenge for the researchers for a long time because of emergence of drug
      resistance. The availability of its genome sequence has opened new avenues for
      research. Antimalarial drugs like chloroquine and mefloquine have been reported
      to inhibit NER pathway mediated repair reactions and thus promote mutagenesis.
      Previous studies have validated existence and implied possible association of
      defective or altered DNA repair pathways with development of drug resistant
      phenotype in certain P. falciparum strains. We conjecture that a compromised NER
      pathway in combination with other DNA repair pathways might be conducive for the
      emergence and sustenance of drug resistance in P. falciparum. Therefore we
      decided to unravel the components of NER pathway in P. falciparum and using
      bioinformatics based approaches here we report a genome wide in silico analysis
      of NER components from P. falciparum and their comparison with the human host.
      Our results reveal that P. falciparum genome contains almost all the components
      of NER but we were unable to find clear homologue for p62 and XPC in its genome.
      The structure modeling of all the components further suggests that their
      structures are significantly conserved. Furthermore this study lays a foundation
      to perform similar comparative studies between drug resistant and drug sensitive
      strains of parasite in order to understand DNA repair-related mechanisms of drug
      resistance. 

PMID- 25757194
TI  - An evidence-based assessment for the association between long-term exposure to
      outdoor air pollution and the risk of lung cancer.
AB  - Although outdoor air pollution has been identified as carcinogenic to humans, the
      magnitude of the relative risk (RR) and the 95% confidence interval (CI) for lung
      cancer in relation to outdoor air pollution remain uncertain. On a global scale,
      we quantified the risk of lung cancer associated with long-term exposure to
      outdoor air pollution using a meta-analytic approach. Relevant cohort studies
      from two databases (PubMed and Web of Science) through 31 May 2014 were searched,
      and a total of 21 cohort studies were identified in the analysis. The risk of
      lung cancer mortality or morbidity increased 7.23 (95% CI: 1.48-13.31)%/10 MUg/m
      increase in fine particles (PM2.5), 13.17 (95% CI: 5.57-21.30)%/10 parts per
      billion (ppb) increase in nitrogen dioxide (NO2), 0.81 (95% CI: 0.14-1.49)%/10
      ppb increase in nitrogen oxides (NOx), and 14.76 (95% CI: 1.04-30.34)%/10 ppb
      increase in sulfur dioxide (SO2). These positive associations remained when
      analysis was restricted to never-smokers or studies with high methodological
      quality, and showed no difference by sex. In addition, the association of fine
      particles with lung cancer was suggestively stronger among never-smokers (RR per
      each 10 MUg/m=1.18, 95% CI: 1.06-1.32). There was a null association for carbon
      monoxide and ozone. Our study indicated that long-term exposure to PM2.5, NO2,
      NOx, and SO2 may be associated with an increased risk of lung cancer. Although
      the magnitude of the RR is relatively small, our finding, if validated, may be of
      public health importance because a large proportion of the population is exposed
      to air pollution globally. 

PMID- 25757195
TI  - The role of pollinators in floral diversification in a clade of generalist
      flowers.
AB  - Pollinator-mediated evolutionary divergence has seldom been explored in
      generalist clades because it is assumed that pollinators in those clades exert
      weak and conflicting selection. We investigate whether pollinators shape floral
      diversification in a pollination generalist plant genus, Erysimum. Species from
      this genus have flowers that appeal to broad assemblages of pollinators.
      Nevertheless, we recently reported that it is possible to sort plant species into
      pollination niches varying in the quantitative composition of pollinators. We
      test here whether floral characters of Erysimum have evolved as a consequence of
      shifts among pollination niches. For this, we quantified the evolutionary
      lability of the floral traits and their phylogenetic association with pollination
      niches. As with pollination niches, Erysimum floral traits show weak phylogenetic
      signal. Moreover, floral shape and color are phylogenetically associated with
      pollination niche. In particular, plants belonging to a pollination niche
      dominated by long-tongued large bees have lilac corollas with parallel petals.
      Further analyses suggest, however, that changes in color preceded changes in
      pollination niche. Pollinators seem to have driven the evolution of corolla
      shape, whereas the association between pollination niche and corolla color has
      probably arisen by lilac-flowered Erysimum moving toward certain pollination
      niches for other adaptive reasons.

PMID- 25757196
TI  - Computer-assisted interpretation of planar whole-body bone scintigraphy in
      patients with newly diagnosed prostate cancer.
AB  - PURPOSE: The aim of this study was to compare the diagnostic properties of EXINI
      Bone(BSI) in newly diagnosed prostate cancer in comparison with expert reading.
      MATERIALS AND METHODS: Bone scintigraphy was performed in consecutive patients
      referred for staging at three clinics (342 patients with DICOM file format, 272
      with Interfile format). Images were reported by three independent readers on a
      four-point scale (class 1-4) and by using a dichotomous outcome (M1 or M0). The
      software analyzed data in balanced mode, as well as using 'patient-specific'
      settings (based on tumor characteristics), and classified outcome as normal (N),
      probably normal (pN), probably abnormal (pA), and abnormal (A). RESULTS:
      Classification of bone metastasis using the software (pA+A) versus experts (class
      3+4) showed a sensitivity of 93.3%, specificity of 89.3%, positive predictive
      value of 57.5%, and negative predictive value of 98.9% with DICOM files. The
      diagnostic properties of the software were notably different with Interfile
      format. For example, expert M1 versus software A showed a sensitivity of 90.0%,
      specificity of 98.9%, positive predictive value of 88.2%, and negative predictive
      value of 98.3% with DICOM files, versus 69.2, 88.2, 38.3, and 96.4% with
      Interfile format, respectively. Generally, patient-specific settings did not
      influence the diagnostic characteristics of the software versus balanced setting
      with expert reading as reference. CONCLUSION: EXINI Bone(BSI) showed high
      sensitivity and specificity for bone metastasis in patients with newly diagnosed
      prostate cancer. The software ruled out metastasis with confidence, whereas the
      positive predictive value was modest. The diagnostic properties were different
      for DICOM and Interfile file formats.

PMID- 25757197
TI  - The assessment of time-of-flight on image quality and quantification with reduced
      administered activity and scan times in 18F-FDG PET.
AB  - OBJECTIVES: The last decade has seen considerable technological innovations in
      PET detectors with the availability, among other advances, of time-of-flight
      (TOF). TOF has been shown to increase the signal-to-noise ratio (SNR), which
      should allow for a reduction in acquired counts while maintaining image quality.
      METHODS: Fifty-eight patients referred for routine F-flurodeoxyglucose ((18)F
      FDG) oncology PET studies were included in this study. Patients with weight below
      or above 100 kg were prescribed 350 or 400 MBq of (18)F-FDG, respectively.
      Listmode data were acquired for 2.5 min per bed position and reconstructed with
      ordered-subset expectation maximization (OSEM) reconstruction. TOF reconstruction
      was performed on reduced-count data, with two levels of reduction (-20 and -40%
      for patients <100 kg and -16 and -30% for patients >100 kg) achieved by clipping
      the listmode data. Liver SNR, mediastinum mean standardized uptake value
      (SUV(mean)), and lesion maximum standardized uptake value (SUV(max)) were
      measured in all images. All images were visually assessed as adequate or
      suboptimal. RESULTS: No significant difference was seen in mediastinum SUV(mean)
      or lesion SUV(max) when comparing reduced-count TOF with full-count OSEM images.
      Compared with the original OSEM images, liver SNR was higher for TOF images using
      the more conservative -20% reduction of counts (P < 0.001, Wilcoxon's signed-rank
      test), whereas no significant statistical difference was seen with -40%
      reductions. CONCLUSION: Incorporation of TOF allows for a reduction in acquired
      counts; this method has been implemented at our institution, with administered
      activity reduced for all patients to 280 MBq and a reduction in scan times for
      all but the largest patients. This has significantly reduced the patient
      radiation dose and improved scanner flexibility and throughput.

PMID- 25757198
TI  - Influence of prior carbimazole on the outcome of radioiodine therapy in pediatric
      and adolescent Graves' disease.
AB  - OBJECTIVE OF THE STUDY: Therapeutic options for pediatric Graves' disease (PGD)
      include antithyroid drug therapy (ATD) as the first line and radioiodine (I-131)
      therapy as the second line of treatment. To date, controversies persist regarding
      the true effect of prior ATD in the outcome of I-131 therapy in PGD. This study
      evaluated the effect of prior carbimazole treatment on the outcome of I-131
      therapy in PGD. METHODS: This is a retrospective study covering the years 1995
      2012, with a median follow-up of 75 months. Records of 114 children (84 girls and
      30 boys, age range: 5-20 years, mean 24-h radioiodine uptake, 58%) who had
      clinically and biochemically proven Graves' disease irrespective of prior ATD
      therapy were included. All patients were treated with fixed doses of 5 mCi (185
      MBq) I-131 for Graves' disease; 74 had undergone prior carbimazole treatment
      (group 1) and 40 were drug naive (group 2). The endpoint of follow-up was stable
      euthyroid or hypothyroid in patients. The effect of prior carbimazole treatment
      on the outcome of I-131 therapy in PGD patients was evaluated. The success of
      radioiodine therapy was defined as the cure of hyperthyroidism. Variables were
      analyzed to identify the potential predictive factors for
      euthyroidism/hypothyroidism after treatment. RESULTS: The cure rate was 70% in
      group 1 and 83% in group 2 with a single dose of radioiodine (P=0.299). The
      success rate achieved at the end of 1-year follow-up in group 1 and group 2 was
      81 and 87%, respectively (P=0.401). No independent predictor was associated with
      success or failure of treatment. At the median follow-up of 75 months (range: 12
      216 months), 76% of patients were hypothyroid on replacement doses of
      levothyroxine and 24% still continued to be euthyroid. CONCLUSION: Prior
      carbimazole treatment does not alter the outcome of radioiodine therapy in PGD.

PMID- 25757199
TI  - Diagnostic value of 99mTc-MDP SPECT/spiral CT combined with three-phase bone
      scintigraphy in assessing suspected bone tumors in patients with no malignant
      history.
AB  - INTRODUCTION: Three-phase bone scintigraphy using technetium-99m-methylene
      diphosphonate is used to diagnose skeletal lesions, whereas single-photon
      emission computed tomography/computed tomography (SPECT/CT) improves the
      diagnostic accuracy of bone disease. We investigated the usefulness of SPECT/CT
      combined with three-phase bone scintigraphy over three-phase bone scintigraphy
      alone in assessing suspected bone tumors in patients with no malignant history.
      MATERIALS AND METHODS: Forty-eight patients (30 men and 18 women; mean age, 43.3
      +/- 20.1 years; age range, 11-82 years) with suspected bone tumors who underwent
      technetium-99m-methylene diphosphonate three-phase bone scintigraphy and SPECT/CT
      between July 2008 and August 2013 were retrospectively reviewed. The lesion from
      each patient was resected or biopsied for pathological confirmation of the
      diagnosis within 3 weeks of the bone scan. All images were interpreted by two
      experienced nuclear medicine physicians who had not been involved in the
      selection of data for the present study. The reviewers were aware of the
      patient's sex, age, and the lesion's site but were unaware of the results of
      other imaging modalities, such as radiography, MRI, and laboratory tests. In
      cases of discrepancy regarding the interpretations, a consensus was reached after
      mutual discussion. The diagnostic ability of three-phase bone scintigraphy and
      SPECT/CT combined with three-phase bone scintigraphy was compared with
      pathological results using the chi(2)-(test, with P-values less than 0.05
      indicating significant differences. Agreement between three-phase bone
      scintigraphy alone or SPECT/CT combined with three-phase bone scintigraphy with
      pathological results was evaluated using kappa scores. RESULTS: Pathological
      results from the 48 lesions of all patients revealed 32 malignant bone tumors and
      16 benign lesions. On using three-phase bone scintigraphy and SPECT/CT combined
      with three-phase bone scintigraphy for the differential diagnosis of bone
      lesions, we found sensitivities to be 96.9 and 100%, specificities to be 31.2 and
      81.3%, positive predictive values to be 73.8 and 91.4%, and negative predictive
      values to be 83.3 and 100%, respectively. The diagnostic accuracies of three
      phase bone scintigraphy alone and SPECT/CT combined with three-phase bone
      scintigraphy were 75.0 and 93.8%, respectively (chi(2) = 5.057; P = 0.025). kappa
      Scores for the agreement of three-phase bone scintigraphy and SPECT/CT combined
      with three-phase bone scintigraphy with pathological results were 0.333 (P =
      0.005) and 0.850 (P < 0.0001), respectively. CONCLUSION: Compared with three
      phase bone scintigraphy, the diagnostic accuracy of SPECT/CT combined with three
      phase bone scintigraphy was higher. SPECT/CT combined with three-phase bone
      scintigraphy is beneficial over three-phase bone scintigraphy for the
      differential diagnosis of suspected bone tumors in patients with no malignant
      history.

PMID- 25757200
TI  - The combined effects of serum lipids, BMI, and fatty liver on 18F-FDG uptake in
      the liver in a large population from China: an 18F-FDG-PET/CT study.
AB  - OBJECTIVES: The aim of the study was to investigate the combined effects of serum
      lipids, BMI, and fatty liver on the liver uptake of fluorine-18
      fluorodeoxyglucose ((18)F-FDG). METHODS: A total of 676 individuals were
      retrospectively studied. The mean standardized uptake value (SUV) was used to
      quantify liver (18)F-FDG uptake. Univariate analyses and multivariate regression
      models identified variables that predicted the mean liver SUV before and after
      dichotomizing participants into low and high BMI groups. RESULTS: The mean liver
      SUV (1.831 +/- 0.417) differed significantly among nutritional categories (P =
      0.005) and degrees of fatty liver (P < 0.001). An increase in mean liver SUV was
      noted in individuals with mild and moderate fatty liver compared with normal
      individuals and in overweight individuals compared with underweight individuals,
      whereas a downward trend was identified in both individuals with severe fatty
      liver and those who were obese. BMI had the strongest association with severity
      of fatty liver (r = 0.443, P < 0.001). Triglyceride, HDL, apolipoprotein-A, age,
      and BMI were independent variables predicting liver SUV mean in the whole
      population, whereas fatty liver severity presented as an independent variable
      only in the low BMI population (P = 0.031). CONCLUSION: BMI, age, triglyceride,
      HDL, and apolipoprotein-A were independent variables predicting liver (18)F-FDG
      uptake. Mild and moderate degree of fatty liver had a positive effect on liver
      (18)F-FDG uptake, whereas a severe degree of fatty liver negatively affected
      (18)F-FDG uptake. Attention should be paid to liver metabolism in patients with
      fatty liver before using liver as the comparator in determining focal (18)F-FDG
      uptake elsewhere within the abdomen.

PMID- 25757201
TI  - The role of 18F-FDG PET/CT in the management of testicular cancers.
AB  - OBJECTIVES: The aim of this study was to determine the utility of fluorine-18
      fluorodeoxyglucose PET/computed tomography ((18)F-FDG PET/CT) in managing
      testicular cancer. PATIENTS AND METHODS: Sixty-two patients (29 seminoma, 28
      nonseminoma and five mixed) underwent 75 (18)F-FDG PET/CT scans (16 scans for
      primary staging, 44 for residual masses and 15 for rising tumour markers). Follow
      up histology, clinical scans and tumour marker results were included for
      retrospective analysis. RESULTS: (i) Primary staging: eight of 11 patients with
      equivocal CT scans had true-negative (18)F-FDG PET/CT scans. Five high-risk
      patients with normal stage 1 CT scans had negative (18)F-FDG PET/CT scans, but
      two subsequently relapsed. (ii) Residual masses: of the 20 scans interpreted as
      showing viable disease, five were false positive. Nineteen scans were negative
      (18 true negative and one false negative). (iii) Rising tumour markers: of the 15
      scans, two were false negative and 13 were true positive. CONCLUSION: (18)F-FDG
      PET/CT is helpful when primary staging CT scans are equivocal but insufficiently
      sensitive to predict relapse in high-risk patients with normal CT scans. With
      residual masses, a negative scan is rarely associated with relapse. (18)F-FDG
      PET/CT is helpful in defining recurrent disease in the majority of patients with
      rising tumour markers and negative CT scans.

PMID- 25757202
TI  - [Self-help friendliness as an element of patient-centered rehabilitation--results
      of a model project].
AB  - BACKGROUND: The concept of self-help friendliness describes a systematic approach
      in health care institutions to strengthen patient-centeredness through closer
      collaboration with self-help groups. Self-help groups enable patients to better
      coping with their diseases. METHOD: Organised as a participatory process 5
      quality criteria for best practice in the cooperation between professionals in
      rehabilitation facilities and patient organizations were developed and tested.
      The process of standards development of ISQUA--International Society for Quality
      in Health Care guided the model project. RESULTS: Implementing the criteria is
      feasible and in line with institution-specific requirements. The process
      documentation is accessible via the network "Selbsthilfefreundlichkeit und
      Patientenorientierung im Gesundheitswesen" (www.selbsthilfefreundlichkeit.de).
      The discussion deals with problems of realization and perspectives concerning the
      transfer of results.

PMID- 25757203
TI  - Role of Intraoperative Radiographs in the Surgical Treatment of Adolescent
      Idiopathic Scoliosis.
AB  - BACKGROUND: One of the main goals of scoliosis surgery is to obtain a balanced
      fused spine. Although preoperative planning remains essential, intraoperative
      posteroanterior radiographs are the only available tool during the procedure to
      verify shoulder and coronal spinal balance and, if necessary, adjust the
      construct. The aim of this study was to quantify the direct influence of
      intraoperative radiographs on the surgical procedure itself during correction of
      adolescent idiopathic scoliosis. METHODS: Retrospective analysis of prospectively
      collected data on a monocentric cohort of adolescent idiopathic scoliosis
      patients undergoing corrective surgery. A total 148 consecutive patients operated
      in the same department following the same validated preoperative planning method
      were included in this prospective radiologic study. The mean follow-up averaged
      33 months. Frontal Cobb angles, T1 tilt, shoulder tilt, iliolumbar angle, and
      frontal balance were measured and compared on intraoperative, early
      postoperative, and latest follow-up radiographs. Any intraoperative modification
      of the correction performed after analysis of the intraoperative radiograph were
      recorded. RESULTS: The analysis of all radiologic parameters was possible in
      90.5% of the cases. In 9.5% of the cases, shoulders could not be properly
      distinguished. Significant modifications on the upper thoracic curve to correct
      T1 tilt or shoulder balance were performed in 29% of the patients, and changes at
      the distal levels were recorded in 19%, underlining planification imperfections.
      On postoperative standing radiographs, the average coronal parameters were
      neutral, without loss of correction at follow-up. CONCLUSIONS: Intraoperative
      radiographs remain necessary to ensure compensation of the shortcomings of the
      modern preoperative planification method.

PMID- 25757204
TI  - Adolescent Patella Instability Extensor Mechanics: Insall Extensor Realignment
      Versus Medial Patellofemoral Ligament Reconstruction.
AB  - BACKGROUND: A plethora of surgical procedures have been promoted in the
      literature regarding the treatment of patella instability in the adolescent
      population; yet, none have compared the joint reaction forces of knee extensor
      mechanics after extensor mechanism realignment (Insall) or medial patellofemoral
      ligament reconstruction (MPFLR). The purpose of this study was to determine if
      there was a difference in knee extensor mechanics between these techniques.
      METHODS: Three cohorts of 10 age-matched adolescents (normal control, Insall, and
      MPFLR) were compared using preoperative magnetic resonance imaging and
      postoperative x-ray in the 2 surgical groups. Patella and patella tendon length
      were measured and the actual moment arm calculated. Compression angles were
      estimated and the effective moment arms determined. Patellofemoral and quadriceps
      joint reaction forces were calculated. Comparisons within and between the 3
      groups were determined and the dependent variables analyzed for statistical
      differences. RESULTS: Mean ages (15.6+/-2.2 y), preoperative measures and
      dependent variables were not different between the groups (P>0.05).
      Postoperatively, there was a significant difference for the patellofemoral joint
      reaction force with respect to the quadriceps force (Fr/Fq), being larger within
      the Insall group (1.08+/-0.08) than the MPFLR group (0.92+/-0.09) (P<0.001). The
      postoperative MPFLR group variables were not significantly different to the
      control group. In contrast, the postoperative Insall group yielded larger joint
      reaction forces compared with control (1.08+/-0.08 vs. 0.83+/-0.11, P<0.001), as
      well as different effective moment arms, Insall versus control (51.23+/-8.8 vs.
      41.9+/-5.9, P<0.001). CONCLUSIONS: Not all surgical interventions for recurrent
      patella instability affect knee mechanics similarly. Although an extensor
      realignment procedure may still have indications in children, the treating
      surgeon should be aware that it does not appear to restore normal joint
      mechanics. CLINICAL RELEVANCE: The Insall-type procedure may increase the
      patellofemoral joint reaction forces beyond normal without fully restoring the
      effective moment arms; whereas, MPFL reconstruction appears to restore the
      effective moment arm without excessive joint reaction forces.

PMID- 25757205
TI  - Are Gait Indices Sensitive Enough to Reflect the Effect of Ankle Foot Orthosis on
      Gait Impairment in Cerebral Palsy Diplegic Patients?
AB  - BACKGROUND: Neuromuscular impairments may compromise gait function in patients
      with cerebral palsy (CP). As such, ambulatory children with CP often use ankle
      foot orthosis (AFO) to facilitate and optimize their ability to walk.The aim of
      this study was to evaluate whether the different gait indices, the Gillette Gait
      Index (GGI), the Gait Deviation Index (GDI), and the Gait Profile Score (GPS),
      reflect the improved gait that was previously shown using AFO. METHODS: A
      retrospective analysis of 53 studies on children with spastic diplegic CP. All
      had undergone a comprehensive gait study and were analyzed while walking, both
      barefoot and with their braces, in the same session.Kinematic and temporal
      spatial data were determined and summarized by 3 methods: GPS, GDI, and GGI.
      RESULTS: Significant differences were found between the barefoot condition and
      the AFO conditions for temporal and kinematic parameters: changes in GGI, GDI,
      and GPS were not statistically significant, with an improvement of 9.33% in GGI
      (P=0.448) and no change in GDI and GPS. CONCLUSIONS: The use of AFO in diplegic
      CP children caused a statistically significant improvement in temporal and
      kinematic parameters. Interestingly, it was found that this improvement was not
      reflected by GGI, GDI, or GPS.These findings might suggest that gait indices, as
      outcome measures, may sometimes not reflect all the effects of specific
      interventions. LEVEL OF EVIDENCE: Level III-retrospective study.

PMID- 25757206
TI  - Surgical Treatment of Intra-articular Knee Venous Malformations: When and How?
AB  - BACKGROUND: To assess the efficacy of surgical treatment of intra-articular knee
      venous malformations (VM). METHODS: Between 1998 and 2010, 8 children (mean age:
      12.3 y) underwent surgical resection of their vascular malformation (7 venous and
      1 capillary venous) involving the knee joint. The lesion was diffuse in 6 cases
      and well-demarcated in 2 cases. All children were suffering from knee pain and
      had recurrent hemarthroses. Color-Doppler ultrasonography, magnetic resonance
      imaging, computed tomography scan, and blood test were performed preoperatively.
      Preoperative and postoperative physical examination, clinical symptoms, and
      orthopaedic evaluation were retrospectively reviewed. Surgery consisted in
      arthrotomy with total excision of the vascular malformation for the 2 well
      demarcated lesions and synovectomy with squeezing of the surrounding vascular
      malformation for 5 diffuse lesions. One patient with an extensive venous
      malformation associated with severe localized intravascular coagulopathy and mild
      hemophilia A had undergone synovectomy by knee arthroscopy. RESULTS: Immediate
      postoperative follow-up was uneventful in 6 patients, whereas 2 patients with
      diffuse vascular malformation and coagulopathy suffered from postoperative
      hemarthroses, delaying their rehabilitation. After a mean follow-up of 5.1 years,
      persistence of the VM within the joint was observed in the 6 initially diffuse
      lesions. The 2 well-demarcated lesions showed no evidence of disease at latest
      follow-up. Four patients with preoperative chondropathy and functional impairment
      were not substantially improved regarding their range of knee motion at latest
      follow-up, whereas the 4 others were free of symptoms. Only 1 patient presented a
      recurrent hemarthroses after a 5-year-symptom-free period and had to be
      reoperated. Patients without preoperative chondropathy recovered normal knee
      function mobility. CONCLUSIONS: This retrospective study highlights the
      importance of early surgery in patients with intra-articular venous malformation,
      even if asymptomatic, to prevent joint impairment. For well-demarcated lesions,
      total resection by arthrotomy can provide definitive healing without resuming of
      symptoms. Although diffuse lesions treated by synovectomy still persist in the
      joint, treatment avoids recurrence of hemarthroses and, therefore, protects the
      cartilage from further erosion. LEVEL OF EVIDENCE: Level IV-cases series.

PMID- 25757207
TI  - Pamidronate Treatment to Prevent Reoccurring Fractures in Children With Cerebral
      Palsy.
AB  - BACKGROUND: Some children with cerebral palsy (CP) have frequent fractures due to
      low bone mineral density and receive treatment with pamidronate, an intravenous
      bisphosphonate. Our review evaluates the outcome of pamidronate treatment in
      these children. METHODS: A retrospective chart review was performed, and 32
      patients (14 girls and 18 boys) with CP Gross Motor Function Classification
      System level III (2 patients), IV (3 patients), and V (27 patients) treated with
      5 courses of pamidronate for low mineral density were identified. Patients with a
      minimum of 2 years of follow-up were included in the study. Data collection was a
      review of the demographics and pretreatment, peritreatment, and posttreatment
      fracture history. RESULTS: The mean age at treatment was 11.6 years (range, 2.9
      to 19.6 y). There were 102 fractures (mean duration 2.5 y) pretreatment and 28
      fractures posttreatment. With an average follow-up of 6.4 years, posttreatment
      rate of fracture decreased to 0.10 fractures per year from the pretreatment rate
      of 2.4 fractures per year (P<0.001). The femur was the most common bone fractured
      both pretreatment (54%) and posttreatment (61%); the major site was the distal
      third of the femur. There were 11 fractures during the course of pamidronate
      treatment at a rate of 0.33 fractures per year. Only 11 patients (34%) sustained
      fracture posttreatment. No correlation with fracture pattern or occurrence was
      found with patient age, number of pretreatment fractures, or sex. Most fractures
      were caused by low-energy injuries, and most were managed nonoperatively.
      CONCLUSIONS: In patients with CP and disuse osteoporosis, the most common
      fracture sustained involved the distal femur via low-velocity injury, and most
      fractures were treated nonoperatively. Although the fracture pattern and the
      treatment remained unchanged, reoccurring fractures in these children can be
      effectively treated medically to interrupt the fracturing tendency.

PMID- 25757208
TI  - Radiographic Criteria for Undergoing an Ulnar Shortening Osteotomy in Madelung
      Deformity: A Long-term Experience From a Single Institution.
AB  - BACKGROUND: There are no established guidelines on the age or the severity of
      deformity for which an ulna shortening osteotomy or ulna epiphysiodesis should be
      performed in children and adolescents with Madelung deformity. The purpose of
      this study was to identify radiographic criteria associated with the eventual
      performance for an ulna shortening procedure in this patient population. METHODS:
      We retrospectively identified 41 wrists in 31 Madelung patients (mean+/-SD age
      13.8+/-3.2 y) subjected to surgical correction of their deformity between 1999
      and 2013. We assessed established radiographic criteria (ulnar tilt, lunate
      subsidence, palmar carpal displacement, ulnar variance) at preoperative and
      postoperative visits. Univariate and multivariate analyses were carried out to
      determine which radiographic criteria were associated with the performance of an
      "ulnar shortening procedure" at the first (index) surgical procedure. RESULTS:
      Eleven wrists were subjected to an ulna shortening osteotomy at the index and 5
      at subsequent procedures; 10 cases received an ulnar epiphysiodesis (mean age
      13.4+/-1.5 y). Ulnar shortening at the index procedure was associated with
      significantly higher preoperative lunate subsidence, ulnar variance, and palmar
      carpal displacement. Ulnar variance of >5 mm and lunate subsidence >4 mm resulted
      in a respective 67% and a 53% likelihood of undergoing ulnar shortening
      osteotomy; palmar carpal displacement over 22 mm resulted in a 50% likelihood for
      ulnar shortening. Patients who required a subsequent procedure (n=8) showed a
      significant increase in palmar displacement between surgeries. None of the 10
      cases with a primary ulnar epiphysiodesis received a subsequent ulnar shortening;
      none of those undergoing late ulnar shortenings had an ulna epiphysiodesis at
      their index procedure (at 10.3+/-4.3 y). CONCLUSIONS: Lunate subsidence, ulnar
      variance, and palmar carpal displacement were significant radiographic criteria
      for undergoing an ulnar shortening osteotomy at our institution. A shortening
      osteotomy may be prevented by early ulna epiphysiodesis in skeletally immature
      children older than 10 years of age. LEVEL OF EVIDENCE: Therapeutic level IV-case
      series.

PMID- 25757209
TI  - Adolescent Hip Dislocation Combined With Proximal Femoral Physeal Fractures and
      Epiphysiolysis.
AB  - BACKGROUND: The risks and long-term effects of acute hip dislocation combined
      with proximal femoral physeal fractures and epiphysiolysis have been minimally
      addressed in the literature. This infrequent combination must be understood to
      avoid the major complications of complete separation of proximal femoral
      components during attempted reduction and to predict the probable outcome of
      surgical treatment. METHODS: Medical records and imaging were retrospectively
      reviewed to identify patients with a diagnosis of severe to complete slipped
      capital femoral epiphysis (CFE) or proximal femoral epiphysiolysis in association
      with hip dislocation. The focus included possible anatomic/vascular disruption
      and their consequences. RESULTS: Twelve patients were identified. Nine
      dislocations were posterior; 3 were anterior. In 4 patients, the intact proximal
      femur was dislocated posteriorly. In 3 patients only the femoral neck was
      reduced, whereas the CFE remained dislocated. In 1 patient percutaneous pinning
      was done in the dislocated position before closed reduction. The reduction was
      successful. In 7 patients only the CFE (4 patients) or femoral neck (3 patients)
      was displaced at the initial presentation in the emergency room. One patient
      presented with posterior dislocation associated with complete separation of both
      components. Ten patients underwent open reduction and internal fixation. Two
      patients had closed reduction. Nine patients developed complete avascular
      necrosis, progressive collapse of the femoral head, and degenerative arthritis.
      Three subsequently had a total hip arthroplasty. One patient developed ischemic
      change limited to the femoral neck and a nonunion through the epiphysis. One
      patient had incomplete ischemic necrosis. Only 1 patient had no evidence of
      ischemic necrosis. CONCLUSIONS: This combination of injuries has several anatomic
      variations. Leaving the CFE dislocated while reducing only the femoral neck must
      be avoided. Reduction should be done in the operating room with muscle
      relaxation. The emergency room is not the venue for reduction. The risk of
      avascular necrosis is extremely high, whether the separation occurs during the
      acute dislocation or attempted reduction. LEVEL OF EVIDENCE: Level IV-case series
      (retrospective review).

PMID- 25757210
TI  - Versatile organic transistors by solution processing.
AB  - A selection of the latest developments in organic electronic materials and
      organic field-effect transistor (OFET) devices is reviewed here with an emphasis
      on the synthetic and manufacturing versatility, ease of processing, and low cost
      offered by solution processability. At the heart of these benefits is the nature
      of the weak van der Waals intermolecular interactions inherent to organic
      compounds. This allows processability with a relatively small amount of energy
      investment. Material solubility, in particular, creates unique pathways for film
      fabrication and the design of new device architectures, while presenting new
      manufacturing challenges to explore. In this review we provide a chronological
      presentation of the important developments in the solution-deposited organic
      small-molecule semiconductor, dielectric, and electrode materials used in OFETs,
      making specific note of current benchmarks. Organic device architectures and
      fabrication methods that are characterized by reduced complexity and ease of
      implementation are discussed. 

PMID- 25757211
TI  - Clinical Outcome of Patients Transplanted with Marginal Donor Lungs via Ex Vivo
      Lung Perfusion Compared to Standard Lung Transplantation.
AB  - BACKGROUND: Lung transplantation is limited by a scarcity of suitable donors
      resulting in high waiting list mortality. Ex vivo lung perfusion (EVLP) allows
      the evaluation and reconditioning of marginal donor lungs for use in
      transplantation. This study aimed to compare clinical outcome of patients
      transplanted with marginal organs by means of EVLP with a standard lung
      transplant cohort through a multicenter open trial. METHODS: Group 1 (n = 9)
      included patients transplanted using EVLP reconditioned marginal lungs. Group 2
      (n = 46) consisted of date-matched patients transplanted using standard
      transplantation of acceptable lungs. The primary composite endpoint included
      acute rejection and infection at 12 months after transplantation. RESULTS: There
      was no significant difference in the overall incidence of acute rejection (P =
      0.754) and the number of treated infection episodes (proven/probable pneumonia; P
      = 0.857/0.368 and proven/probable tracheobronchitis; P = 0.226/0.529) up to 12
      months after transplantation, between group 1 and group 2. Additionally, there
      was no significant difference in early clinical outcome, including intensive care
      unit stay, hospital stay, and 1 year mortality between the two groups (P = 0.338,
      P = 0.112 and P = 0.372, respectively). DISCUSSION: This multicenter study
      demonstrates that EVLP is associated with no adverse effect on clinical outcome,
      including the incidence of acute rejection and infection after lung
      transplantation.

PMID- 25757212
TI  - A Reassessment of the Survival Advantage of Simultaneous Kidney-Pancreas Versus
      Kidney-Alone Transplantation.
AB  - BACKGROUND: Simultaneous kidney and pancreas (SPK) transplantation is an
      attractive option for end-stage renal disease patients with type 1 diabetes.
      Although SPK transplantation is superior to remaining on dialysis, the survival
      advantage for SPK recipients compared to kidney transplantation alone (KTA) is
      controversial. METHODS: Using data obtained from the Scientific Registry of
      Transplant Recipients, we compared patient and graft survivals for 7308 SPK and
      4653 KTA adult patients with type I diabetes transplanted in 1998 to 2009.
      Because SPK and KTA recipients are differently selected, comparison groups were
      chosen to maximize overlap in the case mixes. Most previous studies contrasted
      (unadjusted) Kaplan-Meier survival curves or, if covariate-adjusted, reported
      hazard ratios (HRs). Using newer statistical methods, we avoid relying on hazard
      ratios (which are seldom of inherent interest) and directly compare covariate
      adjusted survival curves. Specifically, we compare average covariate-adjusted SPK
      and KTA-specific survival curves (and 10-year area under the curve; ie,
      restricted mean survival time) to emulate a randomized clinical trial. RESULTS:
      Mean restricted mean kidney graft survival time was significantly greater by 0.18
      years (P = 0.045) for SPK compared to KTA. Similarly, patient survival was 0.17
      years greater (P = 0.033) for SPK than KTA. Increased graft survival was
      primarily observed in younger SPK recipients. Supplementary analysis revealed
      that the SPK hazards were nonproportional, meaning that it would be difficult to
      quantify the cumulative effect of SPK through a standard Cox regression analysis.
      CONCLUSIONS: Using this novel methodology, we demonstrate that SPK is associated
      with statistically but not clinically significant increases in graft and patient
      survival.

PMID- 25757213
TI  - Disease Recurrence and Acute Cellular Rejection Episodes During the First Year
      After Lung Transplantation Among Patients With Sarcoidosis.
AB  - INTRODUCTION: Sarcoidosis is reported to recur after lung transplantation (LT).
      We sought to determine the frequency of recurrent disease after LT and predictors
      of recurrence. We also evaluated the incidence and severity of acute cellular
      rejection (ACR) episodes among these patients. METHODS: The database of LT
      patients at Cleveland Clinic was interrogated for sarcoidosis patients who
      underwent LT between May 1993 and 2011. Charts were reviewed for demographics,
      type of transplant, posttransplant biopsy findings, and outcomes. RESULTS: Data
      were available for 30 patients (mean age, 50 +/- 9.3 years; range, 30-65 years; M
      to-F ratio, 17:13; single-to-double-to-heart lung ratio, 5:24:1). Recurrence of
      sarcoidosis was noted among 7 patients (pathological recurrence in all and
      radiological findings suggesting recurrence in 1 patient) with no impact on
      overall outcomes. Presence of granulomas on explanted lungs was the only
      predictor of recurrence (85.7% vs 30.4%, odds ratio, 13.7; 1.4-136.2; P =
      0.02).Overall burden of ACR episodes on all bronchoscopies was significantly
      lower in patients with disease recurrence (7.6 % vs 21.3% of biopsies, P =
      0.038). Among patients with recurrent disease, ACR did not develop once disease
      recurrence had been seen on transbronchial biopsy. CONCLUSIONS: A significant
      proportion of sarcoidosis patients have disease recurrence after LT and presence
      of active granulomas on explant is associated with subsequent recurrence. There
      may be an association of recurrence with lower frequency of ACR episodes. There
      does not appear to be any impact of sarcoidosis recurrence on 1-, 3-, or 5-year
      survivals.

PMID- 25757214
TI  - Immunosuppression Modifications Based on an Immune Response Assay: Results of a
      Randomized, Controlled Trial.
AB  - BACKGROUND: An immune function assay shows promise for identifying solid organ
      recipients at risk for infection or rejection. The following randomized
      prospective study was designed to assess the clinical benefits of adjusting
      immunosuppressive therapy in liver recipients based on immune function assay
      results. METHODS: Adult liver recipients were randomized to standard practice
      (control group; n = 102) or serial immune function testing (interventional group;
      n = 100) performed with a commercially available in vitro diagnostic assay
      (ImmuKnow; Viracor-IBT Laboratories, Lee's Summit, MO) before transplantation,
      immediately after surgery and at day 1, weeks 1 to 4, 6, and 8, and months 3 to
      6, 9, and 12. The assay was repeated within 7 days of suspected/confirmed
      rejection/infection and within 1 week after event resolution. RESULTS: Based on
      immune function values, tacrolimus doses were reduced 25% when values were less
      than 130 ng/mL adenosine triphosphate (low immune cell response) and increased
      25% when values were greater than 450 ng/mL adenosine triphosphate (strong immune
      cell response). The 1-year patient survival was significantly higher in the
      interventional arm (95% vs 82%; P < 0.01) and the incidence of infections longer
      than 14 days after transplantation was significantly lower among patients in the
      interventional arm (42.0% vs. 54.9%, P < 0.05). The difference in infection rates
      was because of lower bacterial (32% vs 46%; P < 0.05) and fungal infection (2% vs
      11%; P < 0.05). Among recipients without adverse events, the study group had
      lower tacrolimus dosages and blood levels. CONCLUSIONS: Immune function testing
      provided additional data which helped optimize immunosuppression and improve
      patient outcomes.

PMID- 25757215
TI  - Alterations of Endothelial Glycocalyx During Orthotopic Liver Transplantation in
      Patients With End-Stage Liver Disease.
AB  - BACKGROUND: Endothelial glycocalyx participates in the maintenance of vascular
      integrity, and its perturbations cause capillary leakage, loss of vascular
      responsiveness, and enhanced adhesion of leukocytes and platelets. We
      hypothesized that marked shedding of the glycocalyx core protein, syndecan-1,
      occurs in end-stage liver disease (ESLD) and that it increases during orthotopic
      liver transplantation (OLT). We further evaluated the effects of general
      anesthesia on glycocalyx shedding and its association with acute kidney injury
      (AKI) after OLT. PATIENTS AND METHODS: Thirty consecutive liver transplant
      recipients were enrolled in this prospective study. Ten healthy volunteers served
      as a control. Acute kidney injury was defined by Acute Kidney Injury Network
      criteria. RESULTS: Plasma syndecan-1 was significantly higher in ESLD patients
      than in healthy volunteers (74.3 +/- 59.9 vs 10.7 +/- 9.4 ng/mL), and it further
      increased significantly after reperfusion (74.3 +/- 59.9 vs 312.6 +/- 114.8
      ng/mL). The type of general anesthesia had no significant effect on syndecan-1.
      Syndecan-1 was significantly higher during the entire study in patients with
      posttransplant AKI stage 2 or 3 compared to patients with AKI stage 0 or 1. The
      area under the curve of the receiver operating characteristics curve of syndecane
      1 to predict AKI stage 2 or 3 within 48 hours after reperfusion was 0.76 (95%
      confidence interval, 0.57-0.89, P = 0.005). CONCLUSIONS: Patients with ESLD
      suffer from glycocalyx alterations, and ischemia-reperfusion injury during OLT
      further exacerbates its damage. Despite a higher incidence of AKI in patients
      with elevated syndecan-1, it is not helpful to predict de novo AKI. Volatile
      anesthetics did not attenuate glycocalyx shedding in human OLT.

PMID- 25757216
TI  - Aortic Stiffness in a Mortality Risk Calculator for Kidney Transplant Recipients.
AB  - BACKGROUND: The association between aortic stiffness and all-cause mortality in
      kidney transplant recipients (KTRs) is uncertain, and aortic stiffness has not
      yet been incorporated into risk prediction tools. METHODS: During 2007 to 2012,
      we measured carotid-femoral pulse wave velocity (PWV; SphygmoCor apparatus) 8
      weeks after transplantation. The association between PWV and mortality was
      assessed in a Cox regression analysis adjusting for seven risk factors from a
      previously validated model. Internal validation was performed by bootstrap
      resampling, and discrimination and overfitting evaluated by Harrell's C and the
      calibration slope. RESULTS: Of 1497 KTRs, 1040 (69%) had a valid PWV measurement.
      During a median follow-up of 4.2 years, 82 patients died. The association between
      PWV and mortality showed a ceiling effect, and PWV was truncated at 12 m/sec.
      Each 1 m/sec increase in PWV, up to 12 m/sec, was associated with mortality,
      hazard ratio (HR) 1.36 (95% CI, 1.14-1.62; P = 0.001). An interquartile range
      increase (3.8 m/sec) tripled the hazard of mortality, HR, 3.21 (95% CI, 1.63
      6.31), similar to the effect of being approximately 20 years older (interquartile
      range increase (21.6 years); HR, 3.06 [95% CI, 1.87-5.29]). The PWV improved
      model discrimination with an increase in Harrell's C from 0.76 to 0.78; C
      difference, 0.024 (95% CI, 0.005-0.043; P = 0.01). Overfitting was moderate with
      a calibration slope of 0.89, and the final model was adjusted accordingly. A
      spreadsheet version is presented to estimate expected 5-year survival.
      CONCLUSIONS: The PWV is a strong risk factor for mortality in KTRs.

PMID- 25757217
TI  - Recipient-matching of Passenger Leukocytes Prolongs Survival of Donor Lung
      Allografts in Miniature Swine.
AB  - BACKGROUND: Allograft rejection continues to be a vexing problem in clinical lung
      transplantation, and the role played by passenger leukocytes in the rejection or
      acceptance of an organ is unclear. We tested whether recipient-matching of donor
      graft passenger leukocytes would impact graft survival in a preclinical model of
      orthotopic left lung transplantation. METHODS: In the experimental group (group
      1), donor lungs were obtained from chimeric swine, in which the passenger
      leukocytes (but not the parenchyma) were major histocompatibility complex-matched
      to the recipients (n = 3). In the control group (group 2), both the donor
      parenchyma and the passenger leukocytes were major histocompatibility complex
      mismatched to the recipients (n = 3). RESULTS: Lungs harvested from swine
      previously rendered chimeric by hematopoietic stem cell transplantation using
      recipient-type cells showed a high degree of passenger leukocyte chimerism by
      immunohistochemistry and flow cytometry. The chimeric lungs containing passenger
      leukocytes matched to the lung recipient (group 1) survived on average 107 days
      (range, 80-156). Control lung allografts (group 2) survived on average 45 days
      (range, 29-64; P < 0.05). CONCLUSIONS: Our data indicate that recipient-matching
      of passenger leukocytes significantly prolongs lung allograft survival.

PMID- 25757218
TI  - Immunomodulatory Strategies Directed Toward Tolerance of Vascularized Composite
      Allografts.
AB  - BACKGROUND: Achieving tolerance of vascularized composite allografts (VCAs) would
      improve the risk-to-benefit ratio in patients who undergo this life-enhancing,
      though not lifesaving, transplant. Kidney cotransplantation along with a short
      course of high-dose immunosuppression enables tolerance of heart allografts
      across a full major histocompatibility complex (MHC) mismatch. In this study, we
      investigated whether tolerance of VCAs across full MHC disparities could be
      achieved in animals already tolerant of heart and kidney allografts. METHODS:
      Miniature swine that were tolerant of heart and/or kidney allografts long term
      underwent transplantation of myocutaneous VCA across the same MHC barrier. Before
      VCA transplant, group 1 (n = 3) underwent class I-mismatched kidney
      transplantation; group 2 (n = 3) underwent 2 sequential class I-mismatched kidney
      transplantations; group 3 (n = 2) underwent haploidentical MHC-mismatched
      heart/kidney transplantation; and group 4 (n = 2) underwent full MHC-mismatched
      heart/kidney transplantation. RESULTS: All 3 animals in group 1 and 2 of 3
      animals in group 2 showed skin rejection within 85 days; 1 animal in group 2
      showed prolonged skin survival longer than 200 days. Animals in groups 3 and 4
      showed skin rejection within 30 days and regained in vitro evidence of donor
      responsiveness. CONCLUSIONS: This is the first preclinical study in which hearts,
      kidneys, and VCAs have been transplanted into the same recipient. Despite VCA
      rejection, tolerance of heart and kidney allografts was maintained. These results
      suggest that regulatory tolerance of skin is possible but not generally achieved
      by the same level of immunomodulation that is capable of inducing tolerance of
      heart and kidney allografts. Achieving tolerance of skin may require additional
      immunomodulatory therapies.

PMID- 25757220
TI  - Sensitivity, specificity, and predictive values of a forearm blood pressure
      measurement method in severe obesity.
AB  - For blood pressure assessment, it has been reported that forearm blood pressure
      measurement appears to be as valid as an upper-arm blood pressure measurement
      method in individuals with severe obesity when correlated to the intra-arterial
      method, considered as the gold standard. Sensitivity, specificity, and predictive
      values for the presence of systemic hypertension in 25 severely obese patients
      from 352 blood pressure measurements were calculated. The sensitivity (0.98) and
      the positive predictive value (0.93) for hypertension on forearm blood pressure
      measurements are excellent, indicating that the forearm approach is a promising
      alternative to systemic hypertension diagnosis in severe obesity. 

PMID- 25757219
TI  - Role of bone-anabolic agents in the treatment of  breast cancer bone metastases.
AB  - Skeletal metastases are an incurable complication afflicting the majority of
      patients who die from advanced breast cancer. They are most often osteolytic,
      characterized by net bone destruction and suppressed new bone formation. Life
      expectancy from first diagnosis of breast cancer bone metastases is several
      years, during which time skeletal-related events - including pain, fracture,
      hypercalcemia, and spinal cord compression - significantly degrade quality of
      life. The bone marrow niche can also confer hormonal and chemo-resistance. Most
      treatments for skeletal metastases target bone-destroying osteoclasts and are
      palliative. Recent results from the Breast cancer trials of Oral Everolimus-2
      trial suggest that agents such as the mammalian target of rapamycin inhibitor
      everolimus may have efficacy against breast cancer bone metastases in part via
      stimulating osteoblasts as well as by inhibiting tumor growth. Selective estrogen
      receptor modulators similarly inhibit growth of estrogen receptor-positive breast
      cancers while having positive effects on the skeleton. This review discusses the
      future role of bone-anabolic agents for the specific treatment of osteolytic
      breast cancer metastases. Agents with both anti-tumor and bone-anabolic actions
      have been tested in the setting of multiple myeloma, a hematological malignancy
      that causes severe osteolytic bone loss and suppression of osteoblastic new bone
      formation. Stimulation of osteoblast activity inhibits multiple myeloma growth -
      a strategy that might decrease breast cancer burden in osteolytic bone
      metastases. Proteasome inhibitors (bortezomib and carfilzomib) inhibit the growth
      of myeloma directly and are anabolic for bone. Drugs with limited anti-tumor
      activity but which are anabolic for bone include intermittent parathyroid hormone
      and antibodies that neutralize the WNT inhibitors DKK1 and sclerostin, as well as
      the activin A blocker sotatercept and the osteoporosis drug strontium ranelate.
      Transforming growth factor-beta inhibitors have little tumor antiproliferative
      activity but block breast cancer production of osteolytic factors and are also
      anabolic for bone. Some of these treatments are already in clinical trials. This
      review provides an overview of agents with bone-anabolic properties, which may
      have utility in the treatment of breast cancer metastatic to the skeleton.

PMID- 25757222
TI  - Detection rate of (99m) Tc-MIBI single photon emission computed tomography
      (SPECT)/CT in preoperative planning for patients with primary
      hyperparathyroidism: A meta-analysis.
AB  - BACKGROUND: Parathyroid scintigraphy using (99m) Tc-MIBI single photon emission
      computed tomography (SPECT)/CT has been proposed as one of the most accurate
      localization techniques in patients with primary hyperparathyroidism (PHPT). The
      purpose of this review was to meta-analyze published data on the detection rate
      of (99m) Tc-MIBI SPECT/CT in the preoperative planning of patients with PHPT.
      METHODS: A comprehensive literature search of studies published through June 2014
      was performed. The pooled detection rate of this scintigraphic method including
      95% confidence intervals (95% CIs) was calculated on a per patient-based and on a
      per lesion-based analysis by using a random effects model. RESULTS: Twenty-three
      articles including 1236 patients with PHPT were selected. The pooled detection
      rate of (99m) Tc-MIBI SPECT/CT in the preoperative planning of patients with PHPT
      was 88% (95% CI = 84% to 92%) and 88% (95% CI = 82% to 92%) on a per patient
      based and per lesion-based analysis, respectively. CONCLUSION: The (99m) Tc-MIBI
      SPECT/CT has high detection rate for hyperfunctioning parathyroid glands in
      patients with PHPT. (c) 2015 Wiley Periodicals, Inc. Head Neck 38: E2159-E2172,
      2016.

PMID- 25757221
TI  - Maternal filaggrin mutations increase the risk of atopic dermatitis in children:
      an effect independent of mutation inheritance.
AB  - Epidemiological studies suggest that allergy risk is preferentially transmitted
      through mothers. This can be due to genomic imprinting, where the phenotype
      effect of an allele depends on its parental origin, or due to maternal effects
      reflecting the maternal genome's influence on the child during prenatal
      development. Loss-of-function mutations in the filaggrin gene (FLG) cause skin
      barrier deficiency and strongly predispose to atopic dermatitis (AD). We
      investigated the 4 most prevalent European FLG mutations (c.2282del4, p.R501X,
      p.R2447X, and p.S3247X) in two samples including 759 and 450 AD families. We used
      the multinomial and maximum-likelihood approach implemented in the PREMIM/EMIM
      tool to model parent-of-origin effects. Beyond the known role of FLG inheritance
      in AD (R1meta-analysis = 2.4, P = 1.0 x 10-36), we observed a strong maternal FLG
      genotype effect that was consistent in both independent family sets and for all 4
      mutations analysed. Overall, children of FLG-carrier mothers had a 1.5-fold
      increased AD risk (S1 = 1.50, Pmeta-analysis = 8.4 x 10-8). Our data point to two
      independent and additive effects of FLG mutations: i) carrying a mutation and ii)
      having a mutation carrier mother. The maternal genotype effect was independent of
      mutation inheritance and can be seen as a non-genetic transmission of a genetic
      effect. The FLG maternal effect was observed only when mothers had allergic
      sensitization (elevated allergen-specific IgE antibody plasma levels), suggesting
      that FLG mutation-induced systemic immune responses in the mother may influence
      AD risk in the child. Notably, the maternal effect reported here was stronger
      than most common genetic risk factors for AD recently identified through genome
      wide association studies (GWAS). Our study highlights the power of family-based
      studies in the identification of new etiological mechanisms and reveals, for the
      first time, a direct influence of the maternal genotype on the offspring's
      susceptibility to a common human disease. 

PMID- 25757223
TI  - A FRET probe for cell-based imaging of ganglioside-processing enzyme activity and
      high-throughput screening.
AB  - Gangliosides are important signaling molecules in the cell membrane and are
      processed by several enzymes. Deficiencies in these enzymes can cause human
      lysosomal storage diseases. Building an understanding of the pathways of
      glycosphingolipid catabolism requires methods for the analysis of these enzymatic
      activities A GM3-derived FRET probe was synthesized chemoenzymatically for the
      detection and quantitation of a range of ganglioside-degrading enzymes, both in
      cell lysates and in living cells. This is the first substrate that enables the
      ratiometric fluorogenic assay of sphingolipid ceramide N-deacylase and
      endoglycoceramidase and can detect and localize neuraminidase activity in living
      cells. It is therefore a valuable tool for building a better understanding of
      membrane-confined enzymology. It also enables the robust and reliable assay of
      ganglioside-degrading enzymes in a microtiter plate, thus opening the door to
      screening for novel or engineered biocatalysts or for new inhibitors. 

PMID- 25757224
TI  - Hexametaphosphate-Capped Silica Mesoporous Nanoparticles Containing Cu(II)
      Complexes for the Selective and Sensitive Optical Detection of Hydrogen Sulfide
      in Water.
AB  - Cu(II) -macrocycle functionalized hexametaphosphate-capped silica mesoporous
      nanoparticles have been prepared and used for the selective and sensitive
      detection of hydrogen sulfide in aqueous environments. The possibility of using
      different metal complexes combined with different capping anions and choice of
      different dyes or other sensing molecules as indicators makes this new protocol
      highly appealing for the preparation of new sensing systems for sulfide detection
      in different environments. 

PMID- 25757225
TI  - 2-Oxazoline formation for selective chemical labeling of 5-hydroxylysine.
AB  - Hydroxylation of lysine, one of posttranslational modifications of proteins,
      generates 5-hydroxylysine (Koh) and plays a crucial role in regulating protein
      functions in cellular activity. We have developed a chemical labeling method of
      Koh. The 1,2-aminoalcohol moiety of Koh in synthetic peptide sequences was
      trapped by an alkyne-containing benzimidate to form a 2-oxazoline ring. An
      additional ammonia treatment process removed the undesirable amidine residue
      formed between benzimidate and lysine. During the ammonia treatment, the
      oxazoline residue formed at Koh mainly remained intact, and the ring opening to
      the amide form was observed for only part of oxazoline, indicating that the
      chemical labeling is amino acid selective. Azide-substituted biotin or
      fluorescent dye was attached to the peptide through Huisgen cycloaddition at Koh
      and converted into an alkyne-labeled oxazoline form. The Koh-labeling assay could
      provide a platform to enhance proteomic research of lysine hydroxylation. 

PMID- 25757226
TI  - Stable blue thermally activated delayed fluorescent organic light-emitting diodes
      with three times longer lifetime than phosphorescent organic light-emitting
      diodes.
AB  - High quantum efficiency above 18% and extended lifetime three times longer than
      that of phosphorescent organic light-emitting diodes (OLEDs) are demonstrated in
      blue thermally activated delayed fluorescent OLEDs. 

PMID- 25757227
TI  - Bird-flower visitation networks in the Galapagos unveil a widespread interaction
      release.
AB  - Owing to food scarcity and to the high densities that vertebrates often reach on
      islands, typical insect- and seed-eaters widen their feeding niche and interact
      with a greater fraction of species than their mainland counterparts. This
      phenomenon, coined here 'interaction release', has been previously reported for
      single species but never for an entire community. During 4 years, we gathered
      data on bird-flower visitation on 12 Galapagos islands. We show that all sampled
      land birds exploit floral resources and act as potential pollinators across the
      entire archipelago, in all major habitats and all year round. Although species
      and link composition varies among islands, strong interaction release takes place
      on all islands, making their bird-flower network highly generalized. Interaction
      release is crucial to the survival of native birds but simultaneously threatens
      the unique biodiversity of this archipelago, as the birds also visit invading
      plants, likely facilitating their integration into pristine native communities. 

PMID- 25757228
TI  - A public health approach to hepatitis C control in low- and middle-income
      countries.
AB  - In light of new treatment regimens for hepatitis C, Amitabh Suthar and Anthony
      Harries outline a wider public health approach for tackling the disease. 

PMID- 25757229
TI  - [Determination of aniline in water and fish by liquid chromatography-tandem mass
      spectrometry].
AB  - A fast analytical method for the determination of aniline in water and fish meat
      by liquid chromatography-tandem mass spectrometry (LC-MS/MS) has been developed.
      The water sample was mixed with acetonitrile by 4:1 (v/v) and the fish sample was
      extracted by 2.00 mL acetonitrile for each gram of sample, and then the extracts
      of water and fish samples were centrifuged at 5,000 r/min for 5 min. The
      separation was performed on a reversed-phase C18 column using mobile phases of
      acetonitrile-0.5% (v/v) formic acid aqueous solution (85:15, v/v). Aniline was
      separated within 3 min. The calibration curve was linear in the range of 0.5-500
      pg/L with R2 > 0.999. The limits of detection (LODs) were 0.50 MUg/L and 1.00
      MUg/kg and the limits of quantification (LOQs) were 1.00 MUg/L and 2.00 MUg/kg
      for aniline in water and fish meat, respectively. The average recoveries of
      aniline in water were 93.7% at the spiked level of 40 ng and 86.7% at the spiked
      level of 400 ng (n = 5). The average recoveries of aniline in fish were 96.8%,
      92.6% and 81.8% at the spiked levels of 5, 50 and 500 ng respectively (n = 5).
      The relative standard deviations were 1.5%-9.2%. Thirteen water samples and
      twelve fish samples were collected from a reservoir polluted by aniline and the
      maximum contents found were 1,943. 6 MUg/L in water and 60.8 MUg/kg in fish. The
      method is suitable for the determination of aniline residues in water and fish
      with the characteristics of easy operation, high accuracy and precision.

PMID- 25757231
TI  - Septo-optic dysplasia: A reappraisal.

PMID- 25757230
TI  - Posterior fossa arteriovenous malformations.

PMID- 25757233
TI  - Going solar.

PMID- 25757232
TI  - BME trends around the world: from Baby X to frugal technologies, here's what
      biomedical engineers are excited about in 2015.

PMID- 25757234
TI  - A history of the convolution operation.

PMID- 25757235
TI  - Are you receiving the mentorship you need?

PMID- 25757236
TI  - Characterization of succinic semialdehyde dehydrogenase from Aspergillus niger.
AB  - The catabolism of fungal 4-aminobutyrate (GABA) occurs via succinic semialdehyde
      (SSA). Succinic semialdehyde dehydrogenase (SSADH) from the acidogenic fungus
      Aspergillus niger was purified from GABA grown mycelia to the highest specific
      activity of 277 nmol min(-1) mg(-1), using phenyl Sepharose and DEAE Sephacel
      chromatography. The purified enzyme was specific for its substrates SSA and NAD+.
      The substrate inhibition observed with SSA was uncompetitive with respect to
      NAD+. While product inhibition by succinate was not observed, NADH inhibited the
      enzyme competitively with respect to NAD+ and noncompetitively with respect to
      SSA. Dead-end inhibition by AMP and p-hydroxybenzaldehyde (pHB) was analyzed. The
      pHB inhibition was competitive with SSA and uncompetitive with NAD+; AMP competed
      with NAD+. Consistent with the kinetic data, a sequential, ordered Bi Bi
      mechanism is proposed for this enzyme.

PMID- 25757237
TI  - A spatial model showing differences between juxtacrine and paracrine mutual
      oocyte-granulosa cells interactions.
AB  - The bidirectional communication between oocytes and granulosa cells are mediated
      by several factors via a local feedback loop(s). The current model was carried
      out to study the spatial mutual interaction of porcine denuded oocytes and
      granulosa cells either in direct contact (juxtacrine) or paracrine co-culture
      using transwell system. Transwell 0.4 MUm polyester membrane inserts were used to
      permit oocytes-granulosa cells paracrine communication with a distance of 2 mm
      between them in co-culture. Oocytes were cultured with granulosa cells in a
      defined basic maturation medium for 44 h. In results, oocyte secreted factors
      (OSFs; GDF9 and BMP15) temporal expression showed progressive decrement by the
      end of culture in case of direct contact with granulosa cells while it was
      increased progressively in the paracrine co-culture groups. However, oocytes that
      were cultured in direct contact showed a significant increase in blastocyst
      development after parthenogenetic activation than the paracrine co-cultured ones
      (20% vs. 11.5%, respectively). By the end of culture, granulosa cell count in
      direct contact showed a significant decrease than the indirect co-culture group
      (1.2 x 105 cell/mL vs. 2.1 x 10(5) cell/mL, respectively). Steroids (P4 and E2)
      and steriodogenesis enzymes mRNA levels showed significant temporal alterations
      either after 22 h and 44 h of IVM in both juxtacrine and paracrine co-culture
      systems (P <= 0.05). CX43 was much more highly expressed in the granulosa of the
      direct contact group than the indirect co-culture group. These results indicate
      the difference in mutual communication between oocytes and granulosa cells that
      were cocultured either in direct contact (juxtacrine) or with a short distance
      (paracrine) and propose a new paradigm to study different ovarian follicular
      cells interaction.

PMID- 25757238
TI  - Presence of toll like receptor-2 in spleen, lymph node and thymus of Swiss albino
      mice and its modulation by Staphylococcus aureus and bacterial
      lipopolysaccharide. .
AB  - Toll-like receptors (TLR) are a family of pattern recognition receptors
      identifying pathogen associated molecular patterns (PAMPs). They play a critical
      role in the innate immune response during the initial interaction between the
      infecting microorganism and phagocytic cells. Here, we verified the presence of
      TLR-2 in spleen, lymph node and thymus of Swiss albino mice and their modulation
      after infection with Staphylococcus aureus and Lipopolysaccharide (LPS)
      challenge. It was seen that TLR-2 gene transcribed to its respective mRNA on S.
      aureus infection, in thymus, spleen and lymph node of mice but their levels and
      mode of expression varied. When challenged with LPS no prominent changes in the
      expression of TLR-2 receptor was observed but its expression increased gradually
      with time in the thymus, spleen and lymph node of S. aureus infected mice. TLR-2
      expression was also found enhanced in infected splenic macrophages. By studying
      the serum cytokine profile the functionality of the receptor was measured. The
      results indicate the presence of TLR-2 in thymus, spleen and lymph node of Swiss
      albino strain of mice and that they are modulated by S. aureus.

PMID- 25757239
TI  - Alveolar bone loss induced by chronic ethanol consumption from adolescence to
      adulthood in Wistar rats.
AB  - Though there are literature indicating the bone loss due to alcohol consumption,
      studies on the association between ethanol consumption and periodontal breakdown
      in animals are either scarce or have provided conflicting results. Here, we
      investigated the effects of chronic alcohol exposure from adolescence to
      adulthood on the alveolar bone in rats. Wistar rats were exposed to ethanol (6.5
      g/kg/day) in a solution of 22.5% (w/v) or distilled water (control) by gavage
      from 35 days of age (adolescent) until 90 days (adulthood). Evaluation of the
      bone loss was performed using scanning electronic microscopy, in which the
      distances between the cement-enamel junction and the alveolar bone crest from the
      palatal side of the first molar mandibular were measured. The measurements
      obtained were tabulated and analyzed using Student's t-test. Alcohol-treated
      group revealed greater bone loss in comparison to the control group. These
      findings indicate that heavy chronic alcohol exposure from adolescent to
      adulthood can induce alveolar bone loss in rats associated to absence of
      periodontitis.

PMID- 25757241
TI  - Impact of pectolytic enzyme on the fermentation time and free-run juice rate of
      Sharad red wine.
AB  - We evaluated the effect of addition of commercially available pectolytic enzyme
      preparations in the must from Sharad variety, cultivated in India and its
      influence on some oenological parameters of red wine. The small scale
      fermentations demonstrated marked difference of organoleptic (colour) and
      rheologic characteristics (filterability, settling rates) and aroma between
      enzyme treated samples and control samples. We observed 29% enhancement in free
      run juice yield and a remarkable 43% reduction in the fermentation time compared
      to the control. This biotechnological approach has demonstrated the economic
      feasibility and the benefits of adding 0.05 g. Kg(-1) grapes pectolytic enzyme in
      terms of yield, aroma, colour, clarity and fermentation period.

PMID- 25757240
TI  - Identification and characterization of a potent anticancer fraction from the leaf
      extracts of Moringa oleifera L.
AB  - Anticancer potential of Moringa oleifera L. extracts have been well established.
      However, there are no reports on the isolated molecules/fractions from these
      extracts which are responsible for the anticancer/cytotoxic activity. Thus, in
      the present study, we explored the same. The n-hexane, chloroform, ethyl acetate,
      methanol extracts of the M. oleifera leaves and 15 fractions (F1 to F15) of ethyl
      acetate extract were evaluated for their in vitro and in vivo anticancer activity
      using Hep-2 cell lines and Dalton's lymphoma ascites model in mice, respectively.
      Among the tested samples, the F1 fraction showed potential cytotoxic effect in
      Hep-2 cell lines with a CTC50 value of 12.5 +/- 0.5 MUg/ml. In vivo studies with
      the doses 5 and 10 mg/kg, p.o. demonstrated significant reduction in body weight
      and increased the mean survival time compared to the control group. These results
      were also comparable to the standard, 5-Fluorouracil, treated animals. We have
      also successfully isolated and characterized the anticancer fraction, F1 from the
      leaves of M. oleifera L.

PMID- 25757242
TI  - Biological control of the grapevine diseases 'grey mold' and 'powdery mildew' by
      Bacillus B27 and B29 strains.
AB  - Uncinula necator and Botrytis cinerea are the most destructive pathogens of the
      grapevine in Tunisia and elsewhere. We used two strains of Bacillus subtilis
      group, B27 and B29 to control powdery mildew and the grey mold disease of the
      grapevine. Green house experiments showed that B29 and B27 strains of the
      bacteria efficiently reduced the severity of powdery mildew up to 50% and 60%,
      respectively. Further, they decreased Botrytis cinerea development on grape leaf
      by 77% and 99%, respectively. The mode of action has been shown to be
      chitinolytic. These two bacteria showed significant production of total proteins
      discharged into the culture medium. Determination of some chitinolytic enzymes
      revealed the involvement of N-acetyl glucosaminidase (Nagase), the chitin-1,4
      chitobiosidase (Biase) and endochitinase in degrading the mycelium of B. cinerea.

PMID- 25757243
TI  - Plant growth promotion and root colonization by EPS producing Enterobacter sp.
      RZS5 under heavy metal contaminated soil.
AB  - The heavy metal resistant bacterium isolated from field soil and identified as
      Enterobacter sp. RZS5 tolerates a high concentration (100-2000 MUM) of various
      heavy metal ions such as Mn2+, Ni2+, Zn2+, Cu2+, CO2+ and Fe2+ when grown in such
      environment and produces exopolysaccharides (EPS). Here, we have demonstrated EPS
      production by Enterobacter sp. RZS5 during 60 h of growth in yeast extract
      mannitol broth (YEMB). The yield increased by two fold after the addition of 60
      MUM of Ca2+; 50 MUM of Fe2+ and 60 MUM of Mg2+ ions in YEMB, and the optimization
      of physico-chemical parameters. EPS was extracted with 30% (v/v) of isopropanol
      as against the commonly used 50% (v/v) isopropanol method. EPS-rich broth
      promoted seed germination, shoot height, root length, number of leaves and
      chlorophyll content of wheat (Triticum aestivum) seed and peanut (Arachis
      hypogaea) seed. The higher colony-forming unit of Enterobacter sp. in soil
      inoculated with EPS rich broth of Enterobacter sp. indicated the root colonizing
      potential and rhizosphere competence of the isolate. The FTIR spectra of the EPS
      extract confirmed the presence of the functional group characteristics of EPS
      known to exhibit a high binding affinity towards certain metal ions. This overall
      growth and vigour in plants along with the effective root colonization, reflected
      the potential of the isolate as an efficient bio-inoculant in bioremediation.

PMID- 25757244
TI  - Protein interaction networks associated with cardiovascular disease and cancer:
      exploring the effect of bias on shared network properties.
AB  - The human network of Protein-Protein Interactions (PPIs) (interactome) provides
      information on biological systems that can be used to aid prediction of protein
      function and disease association. As some classes of protein may be the focus of
      much study, data sets may contain bias, which may affect the results of network
      analyses. Implicated cancer proteins and proteins including significant known
      mediators of cardiovascular disease (cvd) display a tendency to play a central
      role in a previously constructed interactome. However, removing possible bias in
      the interactome by only considering interactions obtained from non-targeted
      approaches affects the significance of the findings.

PMID- 25757245
TI  - Applying Agrep to r-NSA to solve multiple sequences approximate matching.
AB  - This paper addresses the approximate matching problem in a database consisting of
      multiple DNA sequences, where the proposed approach applies Agrep to a new
      truncated suffix array, r-NSA. The construction time of the structure is linear
      to the database size, and the computations of indexing a substring in the
      structure are constant. The number of characters processed in applying Agrep is
      analysed theoretically, and the theoretical upper-bound can approximate closely
      the empirical number of characters, which is obtained through enumerating the
      characters in the actual structure built. Experiments are carried out using
      (synthetic) random DNA sequences, as well as (real) genome sequences including
      Hepatitis-B Virus and X-chromosome. Experimental results show that, compared to
      the straight-forward approach that applies Agrep to multiple sequences
      individually, the proposed approach solves the matching problem in much shorter
      time. The speed-up of our approach depends on the sequence patterns, and for
      highly similar homologous genome sequences, which are the common cases in real
      life genomes, it can be up to several orders of magnitude.

PMID- 25757246
TI  - Network based prediction of protein localisation using diffusion kernel.
AB  - We present NetLoc, a novel diffusion Kernel-based Logistic Regression (KLR)
      algorithm for predicting protein subcellular localisation using four types of
      protein networks including physical PPI networks, genetic Protein-Protein
      Interaction (PPI) networks, mixed PPI networks and co-expression networks. NetLoc
      is applied to yeast protein localisation prediction. The results showed that
      protein networks can provide rich information for protein localisation
      prediction, achieving Area Under Curve (AUC) score of 0.93. We also showed that
      networks with high connectivity and high percentage of co-localised PPI lead to
      better prediction performance. Investigation showed that NetLoc is a very robust
      approach which can produce good performance (AUC = 0.75) only using 30% of
      original interactions and capable of producing overall accuracy greater than 0.5
      only with 20% annotation coverage. Compared to the previous network feature based
      prediction algorithm which achieved AUC scores of 0.49 and 0.52 on the yeast PPI
      network, NetLoc achieved significantly better overall performance with the AUC of
      0.74.

PMID- 25757247
TI  - A semi-supervised, weighted pattern-learning approach for extraction of gene
      regulation relationships from scientific literature.
AB  - Moreover, the large amount of textual knowledge in the existing biomedical
      literature is growing rapidly, and the creation of manual patterns from the
      available literature is becoming more difficult. There is an increasing demand to
      extract potential generic regulatory relationships from unlabelled data sets. In
      this paper, we describe a Semi-Supervised, Weighted Pattern Learning method
      (SSWPL) to extract such generic regulatory information from the literature. SSWPL
      can build new regulatory patterns according to predefined initial patterns from
      unlabelled data in the literature. These constructed regulatory patterns are then
      used to extract generic regulatory information from PubMed abstracts. The results
      presented herein demonstrate that our method can be utilised to effectively
      extract generic regulatory relationships from the literature by using learned,
      weighted patterns through semi-supervised pattern learning.

PMID- 25757248
TI  - OligoSpecificitySystem: global matching efficiency calculation of oligonucleotide
      sets taking into account degeneracy and mismatch possibilities.
AB  - Oligonucleotide sets are widely used in molecular biology to target a group of
      nucleic acid sequences using Polymerase Chain Reaction (PCR)-based technologies.
      Currently, the global matching efficiency of an oligonucleotide set is considered
      to be equal to the lower matching efficiency calculated for each oligonucleotide.
      However, sequences matching the limiting oligonucleotide did not always match the
      other oligonucleotide of the set, resulting in a biased evaluation of the
      matching efficiency. The OligoSpecificitySystem program avoid this bias by
      calculations of the real global matching efficiency of oligonucleotide sets. It
      can process all kinds of oligonucleotide sets, including the number of
      oligonucleotides, base pair degeneracy occurrences or mismatch occurrences.

PMID- 25757249
TI  - Operon prediction by Markov clustering.
AB  - The prediction of operons is a critical step for the reconstruction of
      biochemical and regulatory networks at the whole genome level. In this paper, a
      novel operon prediction model is proposed based on Markov Clustering (MCL). The
      model employs a graph-clustering method by MCL for prediction and does not need a
      classifier. In the cross-species validation, the accuracies of E. coli K12,
      Bacillus subtilis and P. furiosus are 92.1, 86.9 and 87.3%, respectively.
      Experimental results show that the proposed method has a powerful capability of
      operon prediction. The compiled program and test data sets are publicly available
      at http://ccst.jlu.edu.cn/JCSB/OPMC/.

PMID- 25757250
TI  - Mechanisms classification for glycoside hydrolases by sequence and structure
      features using computational methods.
AB  - Glycoside Hydrolases (GHs) have played key roles in the development of biofuels
      as well as many other industries. Research aimed at accurate classification of
      catalytic mechanisms to increase the catalytic activity of GHs is receiving
      extensive attention. The traditional theories or methods used in the study of
      catalytic mechanisms of GHs are limited by reaction conditions. They are not
      suitable for the study of various GHs because different enzymes would show
      devious physicochemical properties. In this paper, a new method is proposed to
      classify and predict the catalytic mechanism of a certain glycoside hydrolase
      according to their sequence and structure features using k-Nearest Neighbor (kNN)
      classifier, Support Vector Machine (SVM), Naive Bayes (NB) Classifier and the
      Multilayer Perception (MLP) Classifier. The classification performance of the
      four computational methods used were evaluated and compared. Experimental results
      show that each classifier has its own advantages, but the kNN classifier is more
      accurate at the overall level. This research also helps us to gain a better
      understanding of the catalytic mechanisms in different GHs.

PMID- 25757251
TI  - Negative correlation based gene markers identification in integrative gene
      expression data.
AB  - Along with the emergence and development of translational biomedicine, more and
      more genetic information has been applied in clinical practice. In the recent
      decade, the discovery of genetic markers for cancer prognosis obtains increasing
      attention and many methods have been developed. The 'element' methods use one or
      two independent genes to judge the Boolean status of disease. The 'set' methods
      use multiple gene markers as a whole to classify patients into different risks.
      And the advanced 'sets' methods use a group of different sets of biomarkers in an
      assembling manner. Either the existed 'set' or 'sets' methods only concern
      positive correlations among genes. However, the negative regulation, negative
      feedback, and functional repression are actually the relevant clues in cancer
      studies. Therefore, in this paper, based on the integrative gene expression data
      organised as gene-time-sample data or gene-sample-source data, we propose to mine
      Negatively Correlated Gene Sets (NCGSs) from multiple datasets, and use them
      along with the maximal positively correlated gene sets for prognosis
      classification. The experiment results suggest the promotions of cancer prognosis
      accuracy and meaningful pathogen relevance of gene markers by NCGS applications.

PMID- 25757252
TI  - Simplified stochastic models with time delay for studying the degradation process
      of mRNA molecules.
AB  - Message RNA (mRNA) is the template for protein synthesis. It carries information
      from DNA in the nucleus to the ribosome sites of protein synthesis in the cell.
      The turnover process of mRNA is a chemical event with multiple small step
      reactions and the degradation of mRNA molecules is an important step in gene
      expression. A number of mathematical models have been proposed to study the
      dynamics of mRNA turnover, ranging from a one-step first order reaction model to
      the linear multi-component models. Although the linear multi-component models
      provide detailed dynamics of mRNA degradation, the simple first-order reaction
      model has been widely used in mathematical modelling of genetic regulatory
      networks. To illustrate the difference between these models, we first considered
      a stochastic model based on the multi-component model. Then a simpler stochastic
      model was proposed to approximate the linear multi-component model. We also
      discussed the delayed one-step reaction models with different types of time
      delay, including the constant delay, exponentially distributed delay and Erlang
      distributed delay. The comparison study suggested that the one-step reaction
      models failed to realise the dynamics of mRNA turnover accurately. Therefore,
      more sophisticated one-step reaction models are needed to study the dynamics of
      mRNA degradation.

PMID- 25757253
TI  - Characterisation of semantic similarity on gene ontology based on a shortest path
      approach.
AB  - Semantic similarity defined on Gene Ontology (GO) aims to provide the functional
      relationship between different GO terms. In this paper, a novel method, namely
      the Shortest Path (SP) algorithm, for measuring the semantic similarity on GO
      terms is proposed based on both GO structure information and the term's property.
      The proposed algorithm searches for the shortest path that connects two terms and
      uses the sum of weights on the path to estimate the semantic similarity between
      GO terms. A method for evaluating the nonlinear correlation between two variables
      is also introduced for validation. Extensive experiments conducted on the PPI
      dataset and two public gene expression datasets demonstrate the overall
      superiority of SP method over the other state-of-the-art methods evaluated.

PMID- 25757254
TI  - A gradient-based adaptive learning framework for online seisure prediction.
AB  - Most of the current epileptic seizure prediction algorithms require much prior
      knowledge of a patient's pre-seizure electroencephalogram (EEG) patterns. They
      are impractical to be applied to a wide range of patients due to a high inter
      individual variability of pre-seizure EEG patterns. This paper proposes an
      adaptive prediction framework, which is capable of accumulating knowledge of pre
      seizure EEG patterns by monitoring long-term EEG recordings. The experimental
      results on five patients indicate that the adaptive prediction framework is
      effective to improve prediction accuracy over time and thus achieve a
      personalized seizure predication for each patient.

PMID- 25757255
TI  - Identification of co-occurring insertions in cancer genomes using association
      analysis.
AB  - Collections of tumor genomes created by insertional mutagenesis experiments,
      e.g., the Retroviral Tagged Cancer Gene Database (RTCGD), can be analysed to find
      connections between mutations of specific genes and cancer. Such connections are
      found by identifying the locations of insertions or groups of insertions that
      frequently occur in the collection of tumor genomes. Recent work has employed a
      kernel density approach to find such commonly occurring insertions or co
      occurring pairs of insertions. Unfortunately, this approach is extremely compute
      intensive for pairs of insertions and even more intractable for triples, etc. We
      present a technique that can efficiently find commonly co-occurring sets of
      insertions (or other genomic features) of any length by applying Association
      Analysis (AA) (frequent pattern mining) techniques from data mining. A comparison
      to the kernel density approach on RTCGD is provided, as well as results of the
      association approach on two other tumor data sets.

PMID- 25757256
TI  - Extracting a cancer model by enhanced ant colony optimisation algorithm.
AB  - Although Ant-Miner has been used with relative ease for datasets with categorical
      data and small-sized feature vectors, microarray datasets, which contain a few
      samples with large amount of genes, are a totally different story. The Ant-Miner
      is an ant colony optimisation algorithm that extracts predictive rules from
      datasets and intrinsically works on discrete values. This study has developed a
      new algorithm, "Enhanced Ant-Miner" (EAM), based on previous works. EAM deals
      with continuous attributes as well as categorical ones and presents its captured
      models in the form of predictive rules. EAM has been tested versus SVM, CN2, K
      means and hierarchical clustering and the results show that EAM is the best in
      the context of predictive accuracy. Additionally, its agent-based nature gives it
      a much more charming ability to speed up the whole process when compared to other
      trivial miners.

PMID- 25757257
TI  - PPI-IRO: a two-stage method for protein-protein interaction extraction based on
      interaction relation ontology.
AB  - Mining Protein-Protein Interactions (PPIs) from the fast-growing biomedical
      literature resources has been proven as an effective approach for the
      identification of biological regulatory networks. This paper presents a novel
      method based on the idea of Interaction Relation Ontology (IRO), which specifies
      and organises words of various proteins interaction relationships. Our method is
      a two-stage PPI extraction method. At first, IRO is applied in a binary
      classifier to determine whether sentences contain a relation or not. Then, IRO is
      taken to guide PPI extraction by building sentence dependency parse tree.
      Comprehensive and quantitative evaluations and detailed analyses are used to
      demonstrate the significant performance of IRO on relation sentences
      classification and PPI extraction. Our PPI extraction method yielded a recall of
      around 80% and 90% and an F1 of around 54% and 66% on corpora of AIMed and
      BioInfer, respectively, which are superior to most existing extraction methods.

PMID- 25757258
TI  - MedChi's efforts paid off during the legislative session!

PMID- 25757259
TI  - Maryland's Medicare waiver: why it should matter to you.

PMID- 25757260
TI  - I guarantee you.

PMID- 25757262
TI  - MedChi accomplishments during the 2013 Maryland legislative session: a recap of
      legislative initiatives impacting physicians and patients.

PMID- 25757261
TI  - Introduction. Protecting confidential health information: cybersecurity concerns
      for physicians.

PMID- 25757263
TI  - Don't go near the watering hole: protect yourself from cyber attacks.

PMID- 25757264
TI  - Cybersecurity and your practice: what you need to know.

PMID- 25757265
TI  - Stop, look and listen! You could be breaking the rules! Five inadvertent HIPPA
      violations by physicians.

PMID- 25757266
TI  - Steps to protect your practice against cyber attacks. Local versus international
      needs.

PMID- 25757267
TI  - Privacy/data breach coverage: protect your practice.

PMID- 25757268
TI  - Voice authentication--enabling secure and convenient access to your personal
      health information.

PMID- 25757269
TI  - Maryland medical assistance increases payment for primary care services.

PMID- 25757270
TI  - Red roses, beautiful eyes, and the tropics.

PMID- 25757271
TI  - [Recent advances in curcumin and its derivatives for treatment of liver
      diseases].
AB  - Curcumin is a principal polyphenolic curcuminoid extracted from turmeric rhizome,
      which has been used for treating inflammation of joints, ulcers, jaundice and
      other disorders in Asian traditional medicine. In recent years, many studies have
      indicated that curcumin plays important roles in treatment of liver diseases.
      Curcumin attenuates liver injury and non-alcoholic fatty liver disease by
      lowering the release of inflammation cytokines, minimizing oxidative stress,
      enhancing the sensitivity of insulin and altering lipid metabolism. Curcumin
      shows potent anti-fibrosis activity, contributing to inhibit the activation of
      hepatic stellate cells and reduce the deposition of extracellular matrix by its
      regulation of PPAR-gamma, NF-KappaB and TGF-beta signaling pathways. Moreover,
      curcumin exhibits anti-cancer effect by inducing G2/M phase cell cycle arrest and
      apoptosis in several hepatoma cell lines. However, poor water solubility and low
      bioavailability of curcumin limit its clinical applications. To overcome its
      limited systemic bioavailability, many new approaches have been explored to
      deliver curcumin effectively. This article focuses on advances in the effects of
      curcumin and its derivatives for treatment of liver injury, non-alcoholic fatty
      liver disease, liver fibrosis and hepatocarcinoma.

PMID- 25757272
TI  - [Progress in the personalized medicine using pharmacometabonomics].
AB  - Pharmacometabonomics, as an emerging branch of system biology, has been
      increasingly used in personalized medicine and showed broad prospects. By means
      of metabonomics, the complicated and detailed metabolic profile of the patient is
      described, thus providing more detailed description of the disease phenotype.
      With this understanding, response of different individuals to the drugs are
      predicted or evaluated through inherent genetic information of the individual
      combined with the environmental factors. As a result, appropriate drugs and
      dosage are chosen, which greatly promotes the realization of the individualized
      therapy goals. This article describes the emerging field of pharmacometabonomics,
      and the research results of personalized medicine based on the
      pharmacometabonomics in recent years are reviewed in detail.

PMID- 25757273
TI  - [Thought and method of reproductive toxicity research in traditional Chinese
      medicine].
AB  - Reproductive toxicity research takes an important place in traditional Chinese
      medicine pre-clinical safety evaluation. Modern reproductive toxicity experiment
      includes drug-related miscarriage, fetal death, teratism, and adverse effects on
      fertility, genital system, embryonic development and fetus, which is different
      from contraindicated in pregnancy in traditional Chinese medicine theory. Now the
      three-phases reproductive toxicity study is the method mainly applied in
      traditional Chinese medicine reproductive toxicity evaluation. Besides that,
      alternative methods of whole embryos culture and embryonic stem cell test are
      also used in traditional Chinese medicine embryo toxicity evaluation. This
      article reviews research progress and pre-clinical evaluation on reproductive
      toxicity of traditional Chinese medicine.

PMID- 25757274
TI  - [Ribozyme riboswitch based gene expression regulation systems for gene therapy
      applications: progress and challenges].
AB  - Robust and efficient control of therapeutic gene expression is needed for timing
      and dosing of gene therapy drugs in clinical applications. Ribozyme riboswitch
      provides a promising building block for ligand-controlled gene-regulatory system,
      based on its property that exhibits tunable gene regulation, design modularity,
      and target specificity. Ribozyme riboswitch can be used in various gene delivery
      vectors. In recent years, there have been breakthroughs in extending ribozyme
      riboswitch's application from gene-expression control to cellular function and
      fate control. High throughput screening platforms were established, that allow
      not only rapid optimization of ribozyme riboswitch in a microbial host, but also
      straightforward transfer of selected devices exhibiting desired activities to
      mammalian cell lines in a predictable manner. Mathematical models were employed
      successfully to explore the performance of ribozyme riboswitch quantitively and
      its rational design predictably. However, to progress toward gene therapy
      relevant applications, both precision rational design of regulatory circuits and
      the biocompatibility of regulatory ligand are still of crucial importance.

PMID- 25757275
TI  - [The prospect of using bioinformatics technology in the field of biological
      medicine in the era of big data].
AB  - With the advanced development of information technology, there is a huge impact
      on various industries for the arrival of big data. In the biomedical field,
      innovative genome sequencing technology enables low-cost, high-throughput, and
      high-speed to become a reality, which leads to an explosive growth in data and
      also appeared in an urgent need to process those massive biological information.
      High performance computing (HPC) along with effective methods is one of the best
      ways to deal with the problem of big data in biomedical field which could serve
      the biomedical development best. We discussed the issues faced in biomedical big
      data processing and concluded that the bioinformatics is an indispensable
      component of biomedical technologies.

PMID- 25757276
TI  - [Progress in the study of Velvet and LaeA proteins and their relation to the
      development and bioactive compounds in medicinal fungi].
AB  - The medicinal fungi, which are of great importance in traditional medicine, are
      facing the problems of wild resources scarcity and low concentration of bioactive
      compounds. Velvet family and LaeA global regulator play a vital role in secondary
      metabolism and developmental programs, which are found in a wide variety of fungi
      ranging from Chytridiomycota to Basidiomycota. This review elaborates the
      structures and functions between Velvet family and LaeA protein. The Velvet
      family which shares the Velvet protein domain, including VeA (Velvet), VelB
      (Velvet like B), VosA (viability of spores A) and VelC (Velvet like C), acts on
      the regulation function is secondary metabolism and developmental programs such
      as asexual and sexual development. Furthermore, the function is affected by
      environmental factors such as light and temperature. LaeA protein which owns S
      adenosylmethionine-dependent methyltransferase domain, coordinately regulates
      development and secondary metabolism by regulating and modifying the Velvet
      proteins. The regulation of LaeA is mediated by light receptor proteins.
      Therefore, clarifying the mechanism of Velvet and LaeA proteins in medicinal
      fungi will pave the way for nurturing medicinal fungi and improving production of
      bioactive compounds.

PMID- 25757277
TI  - [Population pharmacokinetics of vancomycin and prediction of pharmacodynamics in
      the Chinese people].
AB  - Population pharmacokinetics of vancomycin (VAN) in the Chinese patients was
      described by using nonlinear mixed-effects modeling (NONMEM). 619 VAN serum
      concentrations data from 260 patients including 177 males and 83 females were
      collected separately from two centers. A one-compartment model was used to
      describe this sparse data. No significant difference was observed between two
      center datasets by introducing SID covariate. The final model was as CL= (theta
      (base0+ theta(max) x(1 -e(-theta(Age)(Age/72) and V = theta x theta
      (Age)(Age/72). The creatinine clearance (CL(Cr)) and Age were identified as the
      most significant covariate in the final model. Typical values of clearance (CL)
      and volume of distribution (V) in the final model were 2.91 L x h(-1) and 54.76
      L, respectively. Internal model validation by Bootstrap and NPDE were performed
      to evaluate the robustness and prediction of the final model. The median and 95%
      confidence intervals for the final model parameters were based on 1000
      Bootstraps. External model evaluation was conducted using an independent dataset
      that consisted of 34 patients to predict model performance. Pharmacodynamic
      assessment for VAN by AUC (0-24 h) to MIC ratios of over 400 was considered to be
      the best to predict treatment outcomes for patients. AUC (0-24 h) was calculated
      by clearance based on the above population model. The results indicate that the
      conventional dosing regimen probably being suboptimal concentrations in aged
      patients. The approach via population pharmacokinetic of VAN combined with the
      relationship of MIC, Age, CL(Cr) and AUC(0-24 h)/MIC can predict the rational
      dose for attaining efficacy.

PMID- 25757278
TI  - [Embryo-fetus development toxicity of a novel PPAR-delta agonist in rat].
AB  - The study aims to investigate the embryo-fetus development toxicity of the novel
      PPAR-delta agonist HS060098 on SD rats. The pregnant rats that were randomly
      divided into the solvent control group (1% hydroxypropyl methyl cellulose water
      solution) and HS060098 suspension groups (10, 30 and 100 mg x kg(-1) xd(-1)) were
      orally administered with HS060098 suspension or vehicle during the gestation of 6
      -15 days (GD6-15). At termination (GD20), female rats were sacrificed. The
      pregnant females were evaluated by corpora lutea count, implantation sites,
      existence and death of embryos. Fetal sex, weight, externals, variations and
      malformations of viscus and skeleton were observed. The results show that there
      were no significant abnormality in maternal general conditions and fetal
      appearance as well as viscera, but in the 100 mg x kg(-1) x d(-1) group, the
      maternal weight gain decreased greatly (P < 0.01) and the skeletal ossification
      delayed remarkably (P < 0.01); in the 30 mg x kg(-1) xd(-1) group, the fatal and
      litter number of incompletely ossified sternebrae II was higher than those of the
      control group (P < 0.05); the skeletal malformations occurred in all dose groups,
      which indicate that the novel PPAR-delta agonist HS060098 had maternal toxicity
      and adversely effected fetal skeletal development under the experimental
      conditions.

PMID- 25757279
TI  - [Interaction of E3 ligase HUWE1 and eukaryotic translation initiation factor
      eIF4E].
AB  - To explore the regulation of eIF4E, we screened the protein interacting with
      eIF4E from human cDNA library by using yeast two-hybrid system. Several clones
      interacting with eIF4E were identified. One of them was homologous with HUWE1
      (HECT, UBA and WWE domain containing 1, also named as ARF-BP1, HECTH9 or HUWE1).
      Cell co-immunoprecipitation showed that eIF4E could bind to HUWE1 in mammalian
      cells. We also found that HUWE1 bearing the HECT domain is necessary for its
      association with eIF4E.

PMID- 25757280
TI  - [Recombinant human interferon alpha 2b broad-spectrum anti-respiratory viruses
      pharmacodynamics study in vitro].
AB  - This study is to investigate the effect of recombinant human interferon alpha 2b
      against broad-spectrum respiratory viruses in vitro. At the cellular level, the
      effect of the recombinant human interferon alpha 2b on influenza A virus was
      detected using real-time fluorescence quantitative RT-PCR. The effects of the
      recombinant human interferon alpha 2b on influenza B virus, parainfluenza virus,
      respiratory syncytial virus (RSV) and coronavirus were detected using cytopathic
      effect (CPE) method. In this study, the therapeutic index of recombinant human
      interferon alpha 2b anti-HPIV was 1476.63, the therapeutic index of recombinant
      human interferon alpha 2b anti-RSV was 141.37, the therapeutic index of
      recombinant human interferon alpha 2b anti-coronavirus was more than 2820.76, and
      the antiviral effect of recombinant human interferon alpha 2b was better than
      ribavirin (RBV). Recombinant human interferon alpha 2b has a stronger inhibitory
      effect on different influenza A virus RNA than drug control. The therapeutic
      index of recombinant human interferon alpha 2b anti-influenza B virus was 2.74,
      with modest effect. Recombinant human interferon alpha 2b in vitro has broad
      spectrum antiviral activities, low toxicity and high therapeutic index.
      Recombinant human interferon alpha 2b is expected to become the efficient
      medicine in clinical against respiratory viruses, as well as provide better
      services for prevention and treatment of respiratory viruses' infections.

PMID- 25757281
TI  - [Metformin ameliorates beta-cell dysfunction by regulating inflammation
      production, ion and hormone homeostasis of pancreas in diabetic KKAy mice].
AB  - This study is to evaluate the effects of the metformin (Met) on beta cell
      function of diabetic KKAy mice. Female diabetic KKAy mice selected by insulin
      tolerance test (ITT) were divided randomly into two groups. Con group was orally
      administered by gavage with water, Met group with metformin hydrochloride at a
      dose of 0.2 g x kg(-1) for about 12 weeks. ITT and glucose tolerance tests (OGTT)
      were determined. Beta cell function was assessed by hyperglycemic clamp.
      Pancreatic biochemical indicators were tested. The changes of gene and protein
      expression in the pancreas and islets were also analyzed by Real-Time-PCR and
      immunostaining. Met significantly improved glucose intolerance and insulin
      resistance in KKAy mice. Fasting plasma glucose and insulin levels were also
      decreased. In addition, Met markedly increased glucose infusion rate (GIR) and
      elevated the Ist phase and maximum insulin secretion during clamp. It showed that
      Met decreased TG content and iNOS activities and increased Ca(2+) -Mg(2+)-ATPase
      activity in pancreas. Islets periphery was improved, and down-regulation of
      glucagon and up-regulated insulin protein expressions were found after Met
      treatment. Pancreatic mRNA expressions of inflammation factors including TLR4, NF
      kappaB, JNK, IL-6 and TNF-alpha were down-regulated, p-NF-kappaB p65 protein
      levels also down-regulated by Met. And mRNA expressions of ion homeostasis
      involved in insulin secretion including SERCA2 and Kir6.2 were up-regulated by
      Met. Met increased SIRT5 expression level in pancreas of KKAy mice under the
      hyperglycemic clamp. These results indicated that chronic administration of Met
      regulated pancreatic inflammation generation, ion and hormone homeostasis and
      improved beta cell function of diabetic KKAy mice.

PMID- 25757282
TI  - [Derivatization of berberine based on its synergistic antifungal activity with
      fluconazole against fluconazole-resistant Candida albicans].
AB  - Abstract: Our previous work revealed berberine can significantly enhance the
      susceptibility of fluconazole against fluconazole-resistant Candida albicans,
      which suggested that berberine has synergistic antifungal activity with
      fluconazole. Preliminary SAR of berberine needs to be studied for the possibility
      of investigating its target and SAR, improving its drug-likeness, and exploring
      new scaffold. In this work, 13-substitutited benzyl berberine derivatives and N
      benzyl isoquinoline analogues were synthesized and characterized by 1H NMR and
      MS. Their synergetic activity with fluconazole against fluconazole-resistant
      Candida albicans was evaluated in vitro. The 13-substitutited benzyl berberine
      derivatives 1a-1e exhibited comparable activity to berberine, which suggested
      that the introduction of functional groups to C-13 can maintain its activity. The
      N-benzyl isoquinolines, which were designed as analogues of berberine with its D
      ring opened, exhibited lower activity than berberine. However, compound 2b, 2c,
      and 4b showed moderate activity, which indicated that berberine may be
      deconstructed to new scaffold with synergistic antifungal activity with
      fluconazole. The results of our research may be helpful to the SAR studies on its
      other biological activities.

PMID- 25757283
TI  - [The compounds from n-butanol fraction of Alpinia oxyphylla].
AB  - Nine compounds were isolated from the n-butanol fraction of 95% ethanol extract
      of the fruit of Alpinia oxyphylla Miq. with a combination of various
      chromatographic approaches, including MDS resin, silica gel, reverse phase C18
      and preparative HPLC. On the basis of spectroscopic data analysis, they were
      elucidated as (1R, 4R, 10R)-1beta, 4alpha-dihydroxy-11, 12, 13-trinor-5, 6
      eudesmen-7-one (1), 1beta, 4beta-dihydroxy-11, 12, 13-trinor-8, 9-eudesmen-7-one
      (2), oxyphyllenone A (3), oxyphyllenone B (4), rhamnocitrin (5), staphylionoside
      D (6), benzyl-1-O-beta-D-glucopyranoside (7), 2-O-beta-D-glucopyranosyl-(1S)
      phenylethylene glycol (8), and (S)-1-phenylethyl-beta-D-glucopyranoside (9).
      Among them, compound 1 is a new sesquiterpene, named as oxyphyllenone C;
      compounds 8 and 9 are new natural products; compounds 2 and 6 were isolated from
      the genus Alpinia for the first time, and compound 7 was isolated from A.
      oxyphylla for the first time.

PMID- 25757284
TI  - [Chemical constituents of bufadienolides in cinobufacino injection].
AB  - Cinobufacino injection is purified from water extraction of the skin of Bufo bufo
      gargarizans, which has been widely used for various cancers in clinic with
      significant anti-tumor effects. Bufadienolides were regarded as the main active
      constituents of cinobufacino injection in previous reports. In present study, 6
      bufadienolides were isolated and purified from Cinobufacino injection. Their
      structures were identified as 3-epi-psi-bufarenogin (1), psi-bufarenogin (2), 3
      epi-arenobufagin (3), arenobufagin (4), 3-epi-gamabufotalin (5), and 3-oxo
      arenobufagin (6), separately. Among them, 1 and 3 were new compounds, 5 and 6
      were new natural products. Compounds 1, 2 and compounds 3, 4 were two pairs
      configuration isomers at C-3, separately.

PMID- 25757285
TI  - Two new sesquiterpenoids from basidiomycete Tyromyces chioneus.
AB  - Two new sesquiterpenoids, named as tyromols A and B (1 and 2), were isolated from
      cultures of basidiomycete Tyromyces chioneus, along with two previously reported
      15-hydroxy-6 alpha, 12-epoxy-7beta, 10alphaH, 11betaH-spiroax-4-ene (3) and
      agripilol C (4). Compounds 1-4 were separated and purified by silica gel, RP-18,
      Sephadex LH-20 column chromatography. Their structures were elucidated on the
      basis of extensive spectroscopic analysis including IR, MS, 1D and 2D NMR
      experiments.

PMID- 25757286
TI  - [Comparative study of pharmacokinetics and tissue distribution of 8
      cetylberberine and berberine in rats].
AB  - The concentrations of berberine (BBR) and 8-cetylberberine (8-BBR-C16) in rat
      plasma and tissue were determined by RP-HPLC. Both the plasma pharmacokinetics
      characteristic and tissue distribution differences of BBR and 8-BBR-C16 were
      compared to provide experimental data for the mechanism research and further drug
      development. After the oral administrations of BBR and 8-BBR-C16 at the dose of
      80 mg x kg(-1) for rats, the pharmacokinetics result showed that compared with
      BBR, the C(max) and AUC(0-t), of 8-BBR-C16 increased by 2.8 times and 12.9 times
      respectively, t1/2 extended from 3.61 h to 11.90 h. The tissue distribution
      result showed that compared with BBR, the concentration of 8-BBR-C16 in various
      organizations increased and the retention time extended remarkably. The maximum
      concentration was achieved in lung and the highest concentration in it was 3
      731.82 ng x g(-1). After being derived, the C(max) in plasma and bioavailability
      of 8-BBR-C16 increased remarkably and the circulation time in vivo extended. The
      drug concentration in tissue increased remarkably, and the distribution ratio
      changed too, with strong targeting selection in lung.

PMID- 25757287
TI  - [Effect of the chelator Zn-DTPA on the excretion of lead in lead intoxication
      mice detected with ICP-MS].
AB  - To study the lead excretion effect of the chelator Zn-DTPA on the lead
      intoxication mice, inductively coupled plasma mass spectrometry (ICP-MS) was
      applied to detect the lead content of biological samples. The acute lead
      intoxication mice model was established by injecting lead acetate
      intraperitoneally with the dose of 1 mg. Zn-DTPA was administered
      intraperitoneally to mice once daily for five consecutive days 4 h after
      intoxication. Control group, model group, combination of Zn-DTPA and Ca-DTPA
      group were evaluated at the same time. The urine was collected every day. The
      mice were sacrificed in batches in the 2rd, 4th, 6th day. Biological samples
      including urine, whole blood, femur and brain were prepared and nitrated. Lead
      concentration was detected by ICP-MS. The result showed that Zn-DTPA could
      increase lead content in urine markedly and reduce lead content in blood, femur
      and brain.

PMID- 25757288
TI  - [Determination of gamma-aminobutyric acid in human plasma by LC-MS/MS and its
      preliminary application to a human pharmacokinetic study].
AB  - A rapid, sensitive and convenient LC-MS/MS method was developed for the
      determination of gamma-aminobutyric acid (GABA) in human plasma. d2-gamma
      Aminobutyric acid (d2-GABA) was synthesized as internal standard (IS). After
      extraction from human plasma by protein precipitation with acetonitrile, all
      analytes were separated on a Luna HILIC column (100 mm x 3.0 mm, 3 MUm) using an
      isocratic mobile phase of water: acetonitrile: formic acid (20 : 80 : 0.12) with
      a flow rate of 0.5 mL x min(-1). Acquisition of mass spectrometric data was
      performed in multiple reaction monitoring mode (MRM) in positive electrospray
      ionization using the transitions of m/z 104 --> 69 for GABA and m/z 106 --> 71
      for d2-GABA. The method was linear in the concentration range of 5.00 to 1 000 ng
      x mL(-1). The intra- and inter-day precisions were within 9.9%, and accuracy
      ranged from 99.1% to 104%, within the acceptable limit across all concentrations.
      The method was successfully applied to a pharmacokinetic study of GABA tablets in
      healthy Chinese volunteers.

PMID- 25757289
TI  - [Preparation, formation mechanism and preliminary evaluation of oral absorption
      of a Bicyclol-phospholipid complex].
AB  - Bicyclol with benzyl alcohol structure, is a poorly water-soluble drug, used for
      the treatment of chronic hepatitis B. To increase the drug solubility and oral
      bioavailability, a Bicyclol-phospholipid complex was studied on its preparation,
      formation mechanism, and the influence on drug physicochemical properties and
      oral absorption. The complex was prepared by a solvent evaporation method. The
      optimal formulation was selected by orthogonal experimental design, and a
      reasonable evaluating method of the complexation rate was established. Various
      methods, such as differential scanning calorimetry (DSC), X-ray diffraction
      (XRD), Fourier transform infrared spectroscopy (FTIR) and 31P nuclear magnetic
      resonance (31P-NMR), were used to explore the phase state and formation mechanism
      of the complex. The solubility of drug in complex was investigated in water/n
      octanol. Preliminary study of its absorption and liver tissue distribution in
      rats was also carried out. The results showed that Bicyclol and
      phosphatidylcholine can be complexed entirely in the molar ratio 1 : 2. Bicyclol
      was dispersed in phospholipids as amorphous state. They were combined by
      intermolecular hydrogen bond due to charge transfer effect which occurred between
      the two polarities of the double bond between phosphorus and oxygen (P=O) of
      phosphatidylcholine and benzalcohol group of Bicyclol. The solubility of the
      complex compared to the active pharmaceutical ingredient (API) was effectively
      enhanced 5.75 times in water and 7.72 times in n-octanol, separately. In
      addition, drug concentrations were also enhanced 43 times in plasma and 13 times
      in liver with one hour after administering the complex to rats via oral gavage.
      All of these indicated that Bicyclol with benzalcohol group can interact with
      phospholipids to form complex, improving drug's physicochemical properties, thus
      further increasing its absorption and target tissue distribution. This study also
      provided theoretical reference for the research of other benzalcohol derivatives
      complexed with phospholipids.

PMID- 25757290
TI  - [Preparation and characterization of tetrandrine-loaded PLGA nanocomposite
      particles by premix membrane emulsification coupled with spray-drying method].
AB  - For effective inhalable dry-powder drug delivery, tetrandrine-PLGA (polylactic-co
      glycolic acid) nanocomposite particles have been developed to overcome the
      disadvantages of nanoparticles and microparticles. The primary nanoparticles were
      prepared by using premix membrane emulsification method. To prepare second
      particles, they were spray dried. The final particles were characterized by
      scanning electron microscopy (SEM), dry laser particle size analysis, high
      performance liquid chromatography (HPLC), X-ray diffraction (XRD), differential
      scanning calorimetry (DSC), infrared analysis (IR) and confocal laser scanning
      microscope (CLSM). The average size of the primary particles was (337.5 +/- 6.2)
      nm, while that second particles was (3.675 +/- 0.16) MUm which can be decomposed
      into primary nanoparticles in water. And the second particles were solid sphere
      like with the drug dispersed as armorphous form in them. It is a reference for
      components delivery to lung in a new form.

PMID- 25757291
TI  - [Cloning and prokaryotic expression analysis of HDS from Salvia miltiorrhiza
      bge.f.alba].
AB  - According to the designed specific primers of gene fragment based on the Salvia
      miltiorrhiza transcriptome data, with the method of reverse transcription
      polymerase chain reaction (RT-PCR), this study cloned full-length cDNA sequence
      of 1-hydroxy-2-methyl-2-(E)-butenyl-4-diphosphate synthase gene from Salvia
      miltiorrhiza bge.f.alba, this sequence is named as SmHDS and its GenBank
      registration number is KJ746807. SmHDS, 2 529 bp long, contains an ORF of 2 229
      bp, encodes 742 amino acids, including 5' UTR 170 bp and 3' UTR 130 bp. Using
      bioinformatics software, having made a homology analysis of the obtained
      sequence, we can have a conclusion that SmHDS have a close genetic relationship
      with HDS of Salvia miltiorrhiza. Analysis result of prokaryotic expression
      revealed that in Escherichia coli, SmHDS expressed target proteins which in size
      are comparable with the protein predicted. Meanwhile, the 4 factors which can
      influence the protein expression were optimized, the 4 factors are inducing
      temperature, inducing time, IPTG concentrations and density of inducing host
      bacterium (A600). The optimal expression conditions of SmHDS were 30 degrees C
      until the A600 is 0.6, and add IPTG to a final concentration of 0.2 mmol x L(-1),
      and the induction time of 20 h. It provides theoretical basis for the further
      study of the function of 1-hydroxy-2-methyl-2-(E)-butenyl-4-diphosphate synthase
      in the biosynthesis of tanshinone compounds.

PMID- 25757292
TI  - [Simulating climate change effect on aboveground carbon sequestration rates of
      main broadleaved trees in the Xiaoxing'an Mountains area, Northeast China].
AB  - LANDIS Pro 7.0 model was used to simulate the dynamics of aboveground biomass of
      ten broadleaved tree species in the Xiao Xing' an Mountains area under current
      and various climate change scenarios from 2000 to 2200, and carbon content
      coefficients (CCCs) were coupled to cal- culate the aboveground carbon
      sequestration rates (ACSRs) of these species. The results showed that in the
      initial year of simulation, the biomasses and their proportions of Fraxinus
      mandshurica, Phellodendron amurense, Quercus mongolica, Ulmus propinqua, and Acer
      mono were relatively low, while those of Betula costata, Betula platyphylla, and
      Populus davidiana were higher. A trend of rise after decline occurred in ACSR for
      pioneer species in the mid and late periods of simulation years, but ACSRs for
      the other broadleaved tree species were considerably complex. The ACSRs of Q.
      mongolica and Tilla amurensis fluctuated in the ranges of -0.05-0.25 t . hm(-2) .
      10 a(-1) and 0.16-1.29 t . hm(-2) . 10 a(-1) in simulation years, respectively.
      The ACSRs of F. mandshurica, U. propinqua, A. mono, and B. costata showed a trend
      of decline after rise in late simulation years. There were significant
      differences in ACSR for P. amurense and B. davurica among various climate change
      scenarios in the periods of 2050-2100 and 2150-2200, while no significant
      difference in ACSR for the other species would be detected. Difference of
      sensitivity of various species in ACSR for future climate scenarios in the Small
      Khingan Mountains area existed. However, the un- certainty of future climates
      would not yield significant difference in ACSR for most broadleaved tree species.
      Moreover, a time lag would exist in the process of climate change effects on
      temperate forest's ACSR.

PMID- 25757293
TI  - [Spatial heterogeneity of soil organic carbon and nutrients in low mountain area
      of Changbai Mountains].
AB  - Soil samples were collected in Jincang Forest Farm, Wangqing Forestry Bureau to
      study spatial distribution of soil organic carbon (SOC) and nutrients.
      Geostatistics was used to predict their spatial distribution in the study area,
      and the prediction results were interpolated using regression-kriging and
      ordinary kriging. Multiple linear regression was used to study the relationship
      between SOC and spatial factors. The results showed the SOC density (SOCD) at 0
      60 cm was (16.14 +/- 4.58) kg . m(-2). Soil organic carbon decreased
      significantly with the soil depth. With the increasing soil depth, total N, total
      P, total K, available P and readily available K concentrations decreased.
      Stepwise regression analysis showed that SOC had good correlation with elevation
      and cosine of aspect, with the determination coefficient of 0.34 and 0.39,
      respectively (P < 0.01). Soil organic carbon at 0-20 cm and 0-60 cm soil layers
      conformed to Gaussian model and exponential model. Compared with ordinary
      kriging, the prediction accuracy was improved by 18%-58% using regression
      kriging. Regression-kriging interpolation was also applied to study spatial
      heterogeneity of soil total N.

PMID- 25757294
TI  - [Effects of forest gap on seasonal dynamics of soil organic carbon and microbial
      biomass car- bon in Picea asperata forest in Miyaluo of Western Sichuan,
      Southwest China].
AB  - Effects of gap sizes (50, 100 and 150 m2) on seasonal dynamics of soil organic
      carbon (SOC) and microbial biomass carbon (MBC) in soil surface (0-15 cm) and
      subsurface (15-30 cm) were investigated in a 50-year old Picea asperata
      plantation in Miyaluo forest, Western Si- chuan, China. In the four seasons, the
      SOC and MBC contents were higher in the soil surface than in soil subsurface in
      the four treatments, and varied insignificantly in different seasons. Compared
      with the control, the SOC content increased by 35.4%, 21.2% and 10.3% in soil
      surface, and by 45.5%, 25.0% and 12.1% in soil subsurface with the forest gaps of
      50, 100 and 150 m2, respectively. The MBC content increased by 26.7%, 16.7%,
      11.3% and 24.4%, 12.6%, 7.3% in soil surface and subsurface, respectively. There
      were significant negative relationship between soil SOC content and the soil pH
      and moisture, and significant positive relationship between soil SOC content and
      soil temperature. Significant effects of SOC content, soil pH, soil temperature,
      soil moisture on MBC content were observed, suggesting that forest gaps could
      significantly affect envi- ronmental conditions, and increasing gaps could reduce
      microbial activity and decomposition rate and decrease soil SOC and MBC contents.

PMID- 25757295
TI  - [Altitudinal patterns of species richness and species range size of vascular
      plants in Xiaolong- shan Reserve of Qinling Mountain: a test of Rapoport' s
      rule].
AB  - Altitudinal patterns of species richness and species range size and their
      underlying mechanisms have long been a key topic in biogeography and biodiversity
      research. Rapoport's rule stated that the species richness gradually declined
      with the increasing altitude, while the species ranges became larger. Using
      altitude-distribution database from Xiaolongshan Reverse, this study explored the
      altitudinal patterns of vascular plant species richness and species range in
      Qinling Xiaolongshan Reserve, and examined the relationships between species
      richness and their distributional middle points in altitudinal bands for
      different fauna, taxonomic units and growth forms and tested the Rapoport's rule
      by using Stevens' method, Pagel's method, mid-point method and cross-species
      method. The results showed that the species richness of vascular plants except
      small-range species showed a unimodal pattern along the altitude in Qinling
      Xiaolongshan Reserve and the highest proportion of small-range species was found
      at the lower altitudinal bands and at the higher altitudinal bands. Due to
      different assemblages and examining methods, the relationships between species
      distributing range sizes and the altitudes were different. Increasing taxonomic
      units was easier to support Rapoport's rule, which was related to niche
      differences that the different taxonomic units occupied. The mean species range
      size of angiosperms showed a unimodal pattern along the altitude, while those of
      the gymnosperms and pteridophytes were unclearly regular. The mean species range
      size of the climbers was wider with the increasing altitude, while that of the
      shrubs which could adapt to different environmental situations was not sensitive
      to the change of altitude. Pagel's method was easier to support the Rapoport's
      rule, and then was Steven's method. On the contrary, due to the mid-domain
      effect, the results of the test by using the mid-point method showed that the
      mean species range size varied in a unimodal pattern along the altitude, which
      didn't support the Rapoport's rule, and because of the scatter-spot impact, the
      explanatory power of the cross-species method was much lower.

PMID- 25757296
TI  - [Changes in soil organic carbon and soil microbial functional diversity of Carya
      cathayensis plantations under intensive managements].
AB  - The change characteristics of soil organic carbon and microbial function
      diversity in Chinese hickory Carya cathayensis stands with different intensive
      management durations (5, 10, 15 and 20 years) were studied. The results showed
      that soil total organic carbon (TOC), microbial biomass carbon (MBC), water
      soluble organic carbon (WSOC) decreased significantly, while the stability of
      soil C pool increased significantly after the conversion from evergreen and
      deciduous broadleaf forest to intensively-managed forest (IMF). TOC, MBC and WSOC
      in the hickory forest soil decreased by 28.4%, 34.1% and 53.3% with 5-year
      intensive management, and by 38.6%, 48.9% and 64.1% with 20-year intensive
      management, respectively. The proportions of carboxyl C, phenolic C and aromatic
      C in the hickory forest soil all increased significantly, and the aromaticity of
      soil organic C increased by 23.0%. Soil microbial functional diversity decreased
      greatly af- ter intensive management of Chinese hickory forest. Significant
      differences in average well color development (AWCD) were found between the 0-
      and 5-year treatments and the 10-, 15- and 20- year treatments. The microbial
      diversity indexes (H) and evenness indexes (E) in the 0- and 5-year treatments
      were much greater than in the 10- and 20-year treatments. Correlation analysis
      showed that there were significant correlations among soil TOC, WSOC, MBC, AWCD,
      H and E.

PMID- 25757297
TI  - [Multiple-scale analysis on spatial distribution changes of forest carbon storage
      in Heilongjiang Province, Northeast China based on local statistics].
AB  - Taking 4163 permanent sample plots from Chinese National Forest Inventory (CNFI)
      and key ecological benefit forest monitoring plots in Heilongjiang Province as
      basic data, and by using local Moran I and local statistics (local mean and local
      standard deviation), the spatial pattern, spatial variation and spatial
      autocorrelation of forest carbon storage in Heilongjiang Province with four
      bandwidths of 25, 50, 100 and 150 km were investigated, and the change in forest
      carbon storage across 2005 to 2010 was studied. The results showed that the
      spatial distribution of forest carbon storage in Heilongjiang Province had
      significantly positive spatial correlation, which indicated that the changes of
      carbon storage tended to be similar with their neighbors without a non-random
      manner. Forest carbon storage was affected by environmental factors, and the
      spatial heterogeneity strongly existed with a large variation in the study area.
      The spatial distribution of forest carbon storage was significantly different
      between 2005 and 2010 with an increasing trend. Local statistics are useful tools
      for characterizing forest carbon storage change across time and space, which are
      visualized by ArcGIS.

PMID- 25757298
TI  - [Radial variation and time lag of sap flow of Populus gansuensis in Minqin Oasis,
      Northwest].
AB  - Sap flow of tree trunk is very important to reflect the dynamics of physiological
      activities, as well as to estimate the water consumption of individual plant. In
      the present study, we used the thermal dissipation technique to monitor the sap
      flow velocity (J) at four depth loci (i. e. 2 cm, 3 cm, 5 cm, 8 cm) of three
      Populus gansuensis trees (30 year-old) in Minqin Oasis for two consecutive
      growing seasons. The results showed that there were significant differences among
      J values at four depth loci under tree trunk cambium. J value at the 3 cm depth
      locus (J3) of the tree trunk was the highest, and then in sequences, were 2 cm, 5
      cm and 8 cm depth loci (J2, J5 and J8). J value (J3) on typical sunny days in
      June with the highest atmospheric potential evapotranspiration (ET0) was up to
      28.53 g . cm(-2) . h(-1), which was 1.42, 2.74 and 4.4 times of J2, J5 and J8,
      respectively. In the process of diurnal variation of sap flow velocity, the peak
      value time of J at the four depth loci of the tree trunk was different, but the
      differences among them were within 20 min. Furthermore, the peak value time of
      sap flow velocity was very different to that of solar radiation (Rs) and air
      vapour pressure deficit (VPD). The time lag between J and Rs was from 55 to 88
      min on typical sunny days during the main growing seasons (from June to August),
      and, positively related to the depth of the locus under tree trunk cambium, while
      the time lag between J and VPD reached 60-96 min, and was negatively related to
      the depth of the locus. The seasonal variation patterns of J were consistent with
      ET0. With the increase of tree physiological activities, there was a trend that
      the major water transportation layer extended to the interior sapwood. The most
      important meteorological factor was the solar radiation, which primarily drove
      sap flow at different depths of tree trunk. However, the secondary factor changed
      along with the depth, and VPD became increasingly important with increasing the
      depth.

PMID- 25757299
TI  - [Climatic effects on radial growth of Korean pines with different bark forms in
      Liangshui Natural Reserve, Northeast China].
AB  - Dendrochronological techniques including correlation functions and single-years
      analysis were used to study the relationship between the two kinds of Korean pine
      radial growth in Liangshui Natural Reserve and climatic variables, and to assess
      the similarities and differences between Korean pine with coarse bark (Pinus
      koraiensis forma pachidermis) and fine bark (Pinus koraiensis forma leptodermis)
      in response to climate factors, the main affecting factors and whether the
      response relationship could be of long-term stability. The results showed that
      the Korean pine with fine bark was more suitable for dendrochronological study.
      The radial growth of the two kinds of Korean pine was very sensitive to
      environmental variables and their climate responses had no significant differ-
      ences. From 1902 to 2009, meteorological factors in the growing season,
      especially in June were the primary factors affecting the radial growth of the
      two kinds of Korean pine in the study area. The temperature showed a significant
      negative correlation and the precipitation showed a significant positive
      correlation. The Korean pine growing in different periods had a significantly
      different iresponse to meteorological factors. With the rapid rise of temperature
      and drought after 1970, the radial growth of the two kinds of Korean pine was
      more sensitive to the meteorological factors than before, which was especially
      more sensitive to temperature in growing season and PDSI in many seasons.

PMID- 25757300
TI  - [Monitoring on spatial and temporal changes of snow cover in the Heilongjiang
      Basin based on remote sensing].
AB  - This paper extracted and verified the snow cover extent in Heilongjiang Basin
      from 2003 to 2012 based on MODIS Aqua and Terra data, and the seasonal and
      interannual variations of snow cover extent were analyzed. The result showed that
      the double-star composite data reduced the effects of clouds and the overall
      accuracy was more than 91%, which could meet the research requirements. There
      existed significant seasonal variation of snow cover extent. The snow cover area
      was almost zero in July and August while in January it expanded to the maximum,
      which accounted for more than 80% of the basin. According to the analysis on the
      interannual variability of snow cover, the maximum winter snow cover areas in
      2003-2004 and 2009-2010 (>180 x 10(4) km2) were higher than that of 2011 (150 x
      10(4) km2). Meanwhile, there were certain correlations between the interannual
      fluctuations of snow cover and the changes of average annual temperature and
      precipitation. The year with the low snow cover was corresponding to less annual
      rainfall and higher average temperature, and vice versa. The spring snow cover
      showed a decreasing trend from 2003 to 2012, which was closely linked with
      decreasing precipitation and increasing temperature.

PMID- 25757301
TI  - [Ecological characteristics of preferred habitat of reindeer of Daxing'an
      Mountain forest area Northeast China in summer].
AB  - In July and August of 2012 and 2013, habitat selection and use patterns of
      reindeer were studied using both line and strip-transect surveys. Twenty-three
      habitat factors were measured and compared in known reindeer range areas in
      northwestern China. A total of 72 sampling sites were designated as being used by
      reindeer, and 162 sites were designated as unused control plots. The results
      indicated that, compared to the non-used habitat plots, reindeer selected summer
      habitats with higher values in altitude (26.9 +/- 0.8 m), arbor canopy (17.9% +/-
      2.4%), arbor DBH (35.5 +/- 2.1 cm), arbor height (8.2 +/- 0.5 m), arbor density
      (6.9 +/- 0.5 ind . 400 m(-2)) and stump quan- tity (1.3 +/- 0.2 ind . 400 m(-2)),
      and with a lower shrub height (54.2 +/- 2.0 cm). Moreover, reindeer also selected
      habitats at intermediate positions of intermediate slope gradient, which provided
      good water accessibility, more distance from human disturbance and herder
      influence, but bad concealment and lee condition. Results of the principal
      component analysis showed that the disturbance intensity (i. e. residential
      dispersion, anthropogenic-disturbance dispersion), arbor characteristics (arbor
      height and arbor density, arbor DBH and arbor canopy), geography characteristics
      (i. e. slope position, slope aspect and soil moisture), food abundance (ground
      plant cover and shrub cover), openness (concealment and lee condition) and slope
      gradient were the most important factors influencing the habitat selection of
      reindeer in summer. In summary, the summer habitat selection of reindeer is a
      multidimensional process, through which reindeer adapt according to their
      ecological needs of food resources, safety and anti-predation. Furthermore, the
      pattern of habitat selection of reindeer showed that reindeer in China has not
      yet been domesticated, and reindeer populations and their core habitats should be
      conserved from intensive disturbance.

PMID- 25757302
TI  - [Effects of shade and competition of Chenopodium album on photosynthesis,
      fluorescence and growth characteristics of Flaveria bidentis].
AB  - It is necessary to elucidate its growth mechanism in order to prevent and control
      the further spread of Flaveria bidentis, an invasive plant in China. The effects
      of shading (shading rate of 0, 50% and 80%, respectively) and planting pattern
      (single cropping of F. bidentis, single cropping of Chenopodium album and their
      intercropping) on germination rate, fluorescence characteristics and growth
      characteristics of the two plants were investigated. The results showed that
      moderate shading contributed to emergence rate, but emergence rate of F. bidentis
      was not uniform, which was one of important factors as a stronger invader. With
      the increasing light intensity, net photosynthetic rate (Pn), photochemical
      quenching (qP), electron transport rate of PS II (ETR), quantum yield of PS II
      (Y), non-photochemical quenching (qN), water use efficiency (WUE), shoot bio-mass
      rate (SMR), crown width (CW) and dry biomass (DM) increased, specific leaf area
      (SLA) decreased, LMR of F. bidentis significantly increased, LMR of C. album
      changed insignificantly, and the increment of DM of F. bidentis was higher than
      that of C. album. In 80% shade treatment, Pn and DM of F. bidentis were lower
      than those of C. album. In natural light treatment, Pn, qN, WUE and relative
      competitive index (RCI) were the highest, CW and DM of intercropped F. bidentis
      and Pn, Y of C. album were significantly lower than that of the respective single
      treatment. F. bidentis had higher light saturation point (LSP) and light
      compensation point (LCP). In conclusion, the shade-tolerant ability of F.
      bidentis was weaker than that of C. album, but it was reversed in natural light
      treatment. The two plants adapted to the weak light in 80% shade treatment by
      increasing SLA and decreasing LMR. F. bidentis improved competition under natural
      light by increasing SMR and decreasing CW.

PMID- 25757303
TI  - [Soil microbial community structure of monoculture and mixed plantation stands of
      native tree species in south subtropical China].
AB  - The effects of three plantation stands, Erythrophleumf ordii (EF), Pinus
      massoniana (PM), and their mixed plantation (MP), on soil microbial biomass and
      microbial community structure in south subtropical China were studied by the
      method of phospholipid fatty acids (PLFAs) analysis. The results showed that the
      amounts of microbial total PLFAs and PLFAs of each microbial group in these three
      plantation stand soils were significantly higher in dry season than in rainy
      season. In dry season, the amounts of microbial total PLFAs, bacteria PLFAs,
      fungi PLFAs, and actinomycetes PLFAs were the highest in the PM soil, moderate in
      the MP soil, and the lowest in the EF soil. But in rainy season, the amounts of
      microbial total PLFAs, bacteria PLFAs, fungi PLFAs, and arbuscular mycorrhizal
      fungi (AMF) PLFAs in the EF soil were higher than in the MP soil, and were
      significantly higher than in the PM soil. Principal component analysis (PCA)
      indicated that the variations in soil microbial community structure composition
      were affected by both plantation types and seasons. Redundancy analysis (RDA) of
      soil microbial community structure and environmental factors showed that soil
      temperature and moisture, pH, total nitrogen content, and ammonium nitrogen
      content had significant correlations with PLFA signatures. In addition, the ratio
      of fungi PLFAs to bacteria PLFAs in the MP soil was the highest among the three
      stand soils within the whole year, indicating that mixed plantation stands could
      facilitate the stability of the soil ecosystem.

PMID- 25757304
TI  - [Effects of different organic matter mulching on water content, temperature, and
      available nutrients of apple orchard soil in a cold region].
AB  - The effects of different organic matter covers on soil physical-chemical
      properties were investigated in a 'Hanfu' apple orchard located in a cold region.
      Four treatments were applied (weed mulching, rice straw mulching, corn straw
      mulching, and crushed branches mulching), and physical-chemical properties,
      including orchard soil moisture and nutrient contents, were compared among
      treatment groups and between organic matter-treated and untreated plots. The
      results showed that soil water content increased in the plots treated with
      organic matter mulching, especially in the arid season. Cover with organic matter
      mulch slowed the rate of soil temperature increase in spring, which was harmful
      to the early growth of fruit trees. Organic matter mulching treatments decreased
      the peak temperature of orchard soil in the summer and increased the minimum soil
      temperature in the fall. pH was increased in soils treated with organic matter
      mulching, especially in the corn straw mulching treatment, which occurred as a
      response to alleviating soil acidification to achieve near-neutral soil
      conditions. The soil organic matter increased to varying extents among treatment
      groups, with the highest increase observed in the weed mulching treatment.
      Overall, mulching increased alkali-hydrolyzable nitrogen, available phosphorus,
      and available potassium in the soil, but the alkali-hydrolyzable nitrogen content
      in the rice straw mulching treatment was lower than that of the control.

PMID- 25757305
TI  - [Effects of rodents and litter coverage on the seed fate of wild Prunus
      divaricata in wild fruit forest of Tianshan Mountain, Northwest China].
AB  - The dynamic variation characteristics of seed bank and the main factors
      influencing the fate of Prunus divaricata seeds under the pressure of rodent
      predation and litter coverage were investigated with artificial soil seed banks
      from September, 2010 to April, 2013. It was found that there was about 48.3% of
      seeds germinated under the rodent predation disturbance conditions, 50% of the
      seeds was predated in situ or removed, and only about 4% decayed. The artificial
      seed bank formed a short-term persistent soil seed bank without any rodent
      predation disturbance, and the seeds could germinate even though they had been
      stored in the seed bank for three years. Soil burial provided a lower predation
      pressure and promoted the recruitment of wild P. divaricata seedlings, removal
      and predation in situ by animals was an important factor affecting the fate of
      seeds. At the same time, seeds removed and foraged in situ in the control and
      litter coverage samples were significantly less than that in the bare soil
      samples. Ground coverage reduced the removal and predation of seeds by rodents,
      but the effect was not enough to result in more seedlings. Rodent predation and
      removal were the main factors that could affect the seed fate and dynamics of
      seed bank.

PMID- 25757306
TI  - [Periodic characteristics of soil CO2 flux in mangrove wetland of Quanzhou Bay,
      China].
AB  - Mangrove wetland ecosystem in Quanzhou Bay in Fujian Province is newly restored
      with a regular semidiurnal tide. Soil CO2 concentration in the mangrove soil was
      determined by Li-840 portable gas analyzer, and periodic characteristics of soil
      CO2 emission was investigated. The soil CO2 flux in the wetland soil was
      relatively small because the mangrove was young. The change trends of soil CO2
      concentration and flux with time were consistent in Kandelia obovate and
      Aegiceras corniculatum communities in the intertidal periods. The CO2
      concentration and flux in the wetland soil were 557.08-2211.50 MUmol . mol(-1)
      and -0.21-0.40 MUmol . m(-2) . s(-1), respectively. The average CO2 flux in the
      wetland soil was 0.26 MUmol . mol(-1) . s(-1) in the intertidal of morning and
      evening tides (early intertidal) and -0.01 MUmol . m(-2) . s(-1) in the
      intertidal of evening and morning tides (late intertidal), respectively. At the
      same time after the tide, the concentration and flux of CO2 in the mangrove soil
      in early intertidal was higher than that in late intertidal. In early intertidal,
      the relationship between the flux and instantaneous concentration of CO2 in the
      wetland soil was expressed as a bell-shaped curve, and CO2 flux increased first
      and then decreased with the increasing CO2 concentration, which was in conformity
      with Gaussian distribution.

PMID- 25757307
TI  - [Characteristics of soil moisture in artificial impermeable layers].
AB  - For the problem of low water and fertilizer use efficiency caused by nitrate
      nitrogen lea- ching into deep soil layer and soil desiccation in dryland apple
      orchard, characteristics of soil moisture were investigated by means of hand
      tamping in order to find a new approach in improving the water and fertilizer use
      efficiency in the apple orchard. Two artificial impermeable layers of red clay
      and dark loessial soil were built in soil, with a thickness of 3 or 5 cm. Results
      showed that artificial impermeable layers with the two different thicknesses were
      effective in reducing or blocking water infiltration into soil and had higher
      seepage controlling efficiency. Seepage controlling efficiency for the red clay
      impermeable layer was better than that for the dark loessial soil impermeable
      layer. Among all the treatments, the red clay impermeable layer of 5 cm thickness
      had the highest bulk density, the lowest initial infiltration rate (0.033 mm .
      min(-1)) and stable infiltration rate (0.018 mm . min(-1)) among all treatments.
      After dry-wet alternation in summer and freezing-thawing cycle in winter, its
      physiochemical properties changed little. Increase in years did not affect stable
      infiltration rate of soil water. The red clay impermeable layer of 5 cm thickness
      could effectively increase soil moisture content in upper soil layer which was
      conducive to raise the water and nutrient use efficiency. The approach could be
      applied to the apple production of dryland orchard.

PMID- 25757308
TI  - [Effects of sewage sludge compost on the growth and photosynthetic
      characteristics of turfgrass].
AB  - The effects of different dosages (0, 0.8%, 2%, 6% and 10%) of sewage sludge
      compost on the growth and photosynthetic characteristics of three turfgrass, i.
      e., Festuca arundinacea, Lolium perenne and Poa pratensis were studied. The
      results showed that the dosage of 6% had the optimal effects. The plant height,
      leaf area and dry biomass of three turfgrass increased significantly with the
      increasing sewage sludge compost dosage, while the root/shoot ratio decreased
      obviously. Compared with the control, the plant height of F. arundinacea, L.
      perenne and P. pratensis increased by 64.9%-180.8%, 97.3%-200.9% and 39.1%
      156.5%, the leaf area per plant increased by 91.3%-417.4%, 186.4%-394.9% and
      164.6%-508.3% and the dry biomass per plant increased by 333.4%-867.6%, 138.4%
      445.1% and 316.3%-669.2%, respectively. With the increasing dosage of sewage
      sludge compost, the net photosynthetic rate (Pn), transpiration rate (Tr),
      intercellular CO2 concentration (Ci) and water use efficiency (WUE) of F.
      arundinacea increased first and decreased then, the Pn, Tr and WUE of P.
      pratensis showed a significantly increasing trend, while the Ci decreased after
      an initial increase, and the Pn and WUE of L. perenne increased gradually, while
      the Ci and Tr decreased after a gradual increase. With the in- creasing sewage
      sludge dosage, the contents of chlorophyll a and b of the three turfgrass species
      increased markedly, and then decreased when the dosage was more than 6%, but the
      ratio of chlorophyll a/b was little changed.

PMID- 25757309
TI  - [Effects of different irrigation methods on grain quality of japonica rice in
      Huanghuai District of China].
AB  - Abstract: To clarify the effects of different irrigation treatments in paddy
      field on rice gain quality, three irrigation methods, moistening irrigation (0 cm
      water depth), shallow water irrigation (1-2 cm water depth) and deep water
      irrigation (5-6 cm water depth), were established under field condition. In the
      experiment, rice gain physiochemical parameters including grain length, width,
      area and perimeter, amylose and protein contents and RVA profile characteristics
      of 3 rice cultivars (Shengdao 14, Shengdao 2572, Shengdao 18) with excellent
      quality were evaluated. Results showed that grain length, area and perimeter were
      significantly enhanced under shallow water irrigation when compared with the
      other two irrigation methods, while chalky rice rate and chalkiness performed
      conversely. Of all irrigation methods, moistening irrigation produced the highest
      peak viscosity and hot viscosity values, but deep irrigation produced the lowest
      peak viscosity, hot viscosity and final viscosity values. The breakdown, setback,
      consistence values and amylose content of rice grains of 3 varieties displayed
      disparate responses to the 3 irrigation treatments, largely due to the difference
      of genotypes. Shengdao 14 had the best eating quality under moistening irrigation
      and Shengdao 18 under deep irrigation. Correlation analysis indicated that RVA
      profile parameters were significantly related with apparent and physiochemical
      parameters. The relationship between apparent and eating quality was quantified
      by regression and pathway analyses, suggesting that grain area, perimeter and the
      ratio of grain length to width were the main factors controlling breakdown, the
      ratio of grain length to width was for setback, and grain protein and amylose
      contents for consistence.

PMID- 25757310
TI  - [Effects of poplar-amaranth intercropping system on the soil nitrogen loss under
      different nitrogen applying levels].
AB  - Characteristics of soil nitrogen loss were investigated based on field
      experiments in two types of poplar-amaranth intercropping systems (spacing: L1 2
      m x 5 m, L2 2 m x 15 m) with four N application rates, i. e., 0 (N1), 91 (N2),
      137 (N3) and 183 (N4) kg . hm(-2). The regulation effects on the soil surface
      runoff, leaching loss and soil erosion were different among the different types
      of intercropping systems: L1 > L2 > L3 (amaranth monocropping). Compared with the
      amaranth monocropping, the soil surface runoff rates of L1 and L2 decreased by
      65.1% and 55.9%, the soil leaching rates of L1 and L2 with a distance of 0.5 m
      from the poplar tree row de- creased by 30.0% and 28.9%, the rates with a
      distance of 1. 5 m decreased by 25. 6% and 21.9%, and the soil erosion rates
      decreased by 65.0% and 55.1%, respectively. The control effects of two
      intercropping systems on TN, NO(3-)-N and NH(4+)-N in soil runoff and leaching
      loss were in the order of L1 > L2 > L3. Compared with the amaranth monocropping,
      TN, NO(3-)-N and NH(4+)-N loss rates in soil runoff of L1 decreased by 62.9%,
      45.1% and 69.2%, while the loss rates of L2 decreased by 23.4%, 6.9% and 46.2%
      under N1 (91 kg . hm(-2)), respectively. High- er tree-planting density and
      closer positions to the polar tree row were more effective on controlling the
      loss rates of NO(3-)-N and NH(4+)-N caused by soil leaching. The loss proportion
      of NO(3-)-N in soil runoff decreased with the increasing nitrogen rate under the
      same tree-planting density, while that of NH(4+)-N increased. Leaching loss of
      NO(3-)-N had a similar trend with that of NH(4+)-N, i. e. , N3 > N2 > N1 > N0.

PMID- 25757311
TI  - [Effect of ridge & terraced ecological rice farming on rice photosynthetic
      characteristics and yield].
AB  - Taking super hybrid rice Y-liangyou 1, and hybrid rice Xianyou 63 and
      conventional rice Huanghuazhan as test materials, a field experiment was
      conducted in Changsha City of Hunan Province in 2011 and 2012 to investigate the
      effects of ridge & terraced ecological rice farming (RT) and bed ecological rice
      farming (B) on rice grain yield and photosynthetic characteristics. Compared with
      conventional rice farming (CK) , yield of Y-liangyou 1 in the RT was increased
      significantly by 28.7%, the effective panicles per unit area and spikelets per
      panicle were increased by 16.1% and 6.8%, respectively. Yields of Xianyou 63 and
      Huanghuazhan in the RT and B were 24.3% and 19.7%, 12.0% and 16.2% higher than
      those of CK, respectively. Leaf area index, dry matter accumulation before and
      after full-heading, total dry matter accumulation of Y-liangyou 1 in the RT was
      higher than that of CK. Number of spikelets/leaf area, number of filled
      grains/leaf area, grain mass/leaf area of Y-liangyou 1 in the RT were 8.1%, 14.8%
      and 15.8% higher than those of CK, respectively, the photosynthetic potential was
      increased by 32.2% while the net assimilation rate was declined by 9.3%.

PMID- 25757312
TI  - [Effects of drought stress, high temperature and elevated CO2 concentration on
      the growth of winter wheat].
AB  - The impacts of climate change on the grain yield, photosynthesis, and water
      conditions of winter wheat were assessed based on an experiment, in which wheat
      plants were subjected to ambient and elevated CO2 concentrations, ambient and
      elevated temperatures, and low and high water conditions independently and in
      combination. The CO2 enrichment alone had no effect on the photosynthesis of
      winter wheat, whereas higher temperature and drought significantly decreased the
      photosynthetic rate. Water conditions in flag leaves were not significantly
      changed at the elevated CO2 concentration or elevated temperature. However,
      drought stress decreased the relative water content in flag leaves, and the
      combination of elevated temperature and drought reduced the water potential in
      flag leaves. The combination of elevated CO2 concentration, elevated temperature,
      and drought significantly reduced the photosynthetic rate and water conditions,
      and led to a 41.4% decrease in grain yield. The elevated CO2 concentration alone
      increased the grain yield by 21.2%, whereas the elevated temperature decreased
      the grain yield by 12.3%. The grain yield was not affected by the combination of
      elevated CO2 concentration and temperature, but the grain yield was significantly
      decreased by the drought stress if combined with any of the climate scenarios
      applied in this study. These findings suggested that maintaining high soil water
      content might be a vital means of reducing the potential harm caused by the
      climate change.

PMID- 25757313
TI  - [PS II photochemical efficiency in flag leaf of wheat varieties and its
      adaptation to strong sun- light intensity on farmland of Xiangride in Qinghai
      Province, Northwest China].
AB  - Taking four wheat varieties developed by Northwest Institute of Plateau Biology,
      Chinese Academy of Sciences, as test materials, with the measurement of content
      of photosynthetic pigments, leaf area, fresh and dry mass of flag leaf, the PS II
      photochemistry efficiency of abaxial and adaxial surface of flag leaf and its
      adaptation to strong solar radiation during the period of heading stage in
      Xiangride region were investigated with the pulse-modulated in-vivo chlorophyll
      fluorescence technique. The results indicated that flag leaf angle mainly grew in
      horizontal state in Gaoyuan 314, Gaoyuan 363 and Gaoyuan 584, and mainly in
      vertical state in Gaoyuan 913 because of its smaller leaf area and larger width.
      Photosynthetic pigments were different among the 4 varieties, and positively
      correlated with intrinsic PS II photochemistry efficiencies (Fv/Fm). In clear
      days, especially at noon, the photosynthetic photoinhibition was more serious in
      abaxial surface of flag leaf due to directly facing the solar radiation, but it
      could recover after reduction of sunlight intensity in the afternoon, which meant
      that no inactive damage happened in PS II reaction centers. There were
      significant differences of PS II actual and maximum photochemical efficiencies at
      the actinic light intensity (PhiPS II and Fv'/Fm') between abaxial and adaxial
      surface, and their relative variation trends were on the contrary. The
      photochemical and non-photochemical quenching coefficients (qP and NPQ) had a
      similar tendency in both abaxial and adaxial surfaces. Although PhiPS II and qP
      were lower in adaxial surface of flag leaf, the Fv'/Fm' was significantly higher,
      which indicated that the potential PS II capture efficiency of excited energy was
      higher. The results demonstrated that process of photochemical and non
      photochemical quenching could effectively dissipate excited energy caused by
      strong solar radiation, and there were higher adaptation capacities in wheat
      varieties natively cultivated in Qinghai-Tibetan Plateau area.

PMID- 25757314
TI  - [Effects of high temperature on Bt proteins expression and nitrogen metabolic
      physiology in square of Bt cotton at the peak squaring stage].
AB  - Taking Bt cotton Sikang 1 (a conventional cultivar), Sikang 3 (a hybrid cultivar)
      from China and 99B (a conventional cultivar), Daiza 1 (a hybrid cultivar) from
      USA as test materials, the effects of different high temperatures on thesquare Bt
      proteins expression and nitrogen metabolic physiology were investigated. The
      results showed that the square Bt protein contents of the four cultivars
      decreased significantly above 38  degrees C compared with that at 32  degrees C.
      The higher the temperature was above 38  degrees C, the greater the reduction
      extent of the Bt protein content was. The square Bt protein contents of the
      hybrid cultivars were higher than that of the conventional cultivars, and were
      less reduced under the high temperature stress. The cultivars with bigger
      reductions in Bt protein content also showed greater reductions in the square
      soluble protein contents, pyruvic transaminase activities and glutamic
      oxaloacetic transaminase activities, while larger increments were detected for
      the square free amino acid contents, proteinsase activities and peptidase
      activities.

PMID- 25757315
TI  - [Exogenous NO mediated GSH-PCs synthesis pathway in tomato under copper stress].
AB  - Nitric oxide (NO), as a biologically active molecule, widely involved in the
      biotic and abiotic stresses. By using solution culture, this paper reported the
      dynamic changes in enzyme activity and metabolites related to GSH-PCs synthesis
      way mediated by exogenous NO in tomato (Lycopersicon esculentum). The results
      showed that exogenous NO could affect the metabolic pathway of GSH-PCs in tomato
      seedlings under copper stress. Compared with CK, the activity of gamma-ECS and GS
      was significantly activated, consequently resulting in a sharp rise in GSH and
      PCs contents in tomato root. Moreover, gamma-ECS and GS activity, GSH and PCs
      contents constantly rise with the extension of processing time under copper
      stress. Adding exogenous SNP could further improve gamma-ECS and GS activity in
      tomato, and promote the production of GSH and PCs, which contributed to enhancing
      the ability of removing superoxide and chelating excess Cu2+ to reduce its
      biological toxicity. To a certain extent, GSH-PCs metabolic changes in leaf
      lagged behind that in roots. Exogenous BSO could significantly inhibit gamma-ECS
      activity, and applying SNP could significantly reverse the inhibition on GSH and
      PCs synthesis by BSO. BSO had little effects on PCs content in leaf. Under copper
      stress, exogenous NO may initiate a signal mechanism and reduce the biotoxicity
      and oxidative damage caused by excessive Cu2+ by activating or enhancing the
      enzymatic and non-enzymatic systems in the GSH-PCs synthesis path.

PMID- 25757316
TI  - [Effects of exogenous GSH on photosynthetic characteristics and expression of key
      enzyme genes of CO2 assimilation in leaves of tomato seedlings under NaCl
      stress].
AB  - By spraying tomato leaves with reduced glutathione (GSH), oxidized glutathione
      (GSSG) and glutathione synthesis inhibitor (BSO), respectively, the effects of
      glutathion-mediated redox state on leaf photosynthesis in tomato under NaCl
      stress were investigated. The results showed that the application of exogenous
      GSH significantly induced an increase in reducing power level, in- creased the
      net photosynthetic rate (Pn), stomatal conductance (g(s)), transpiration rate
      (Tr), as well as the maximum quantum yield of PS II (Fv/Fm), actual photochemical
      efficiency of PS II (PhiPS II), photochemical quenching coefficient (q(P)) and
      non-photochemical quenching coefficient (NPQ), and enhanced the Rubisco activity
      and expression levels of RbcL, RbcS and RCA genes in leaves of tomato seedlings
      under NaCl stress. These results suggested that GSH alleviated salt-induced
      oxidative stress by protecting PS II from damage caused by excess energy, and
      improving the photochemical efficiency of PS II and dark reaction activity of
      photosynthesis. Although spraying GSSG decreased the level of reducing power and
      further aggravated the damage and photoinhibition of the leaf photosynthetic
      apparatus, Pn was not affected in combined stressed (NaCl and GSSG) plants, which
      might be due to the up-regulation of expression levels of RbcL and RbcS genes.
      The application of BSO had no significant effects on redox state, CO2
      conductivity capacity and PS II photochemical efficiency in tomato leaves under
      NaCl stress. However, compared to salt singly stressed plants, BSO application
      increased Pn, likely due to the up-regulation of Rubisco initial activity and RCA
      and RbcS expression levels.

PMID- 25757317
TI  - [UV-B radiation sensitivity of Salvia miltiorrhiza in different growth periods].
AB  - A pot experiment was conducted to investigate the effects of UV-B radiation on
      sensitive index (SI) synthetically formed by the height, leaf area and biomass,
      and on the accumulation of rosmarinic acid (RA) and salvianolic acid B (SAB) of
      Salvia miltiorrhiza in two growth periods. The results showed the SI in the shoot
      vigorous growth and harvesting periods both decreased with the increasing UV-B
      radiation, but the SI in the latter period was even less. The RA and SAB contents
      in the leaves increased with the increasing UV-B radiation, and the increment was
      greater in the harvesting period than in the shoot vigorous growth period. The RA
      and SAB contents decreased in the roots, and decreased with the increasing UV-B
      intensity and duration. Total contents of RA and SAB in roots decreased to 10.0%
      and 6.3% of the control under the high UV-B intensity in the harvesting period.

PMID- 25757318
TI  - [Effects of biochar and nitrification inhibitor incorporation on global warming
      potential of a vegetable field in Nanjing, China].
AB  - The influences of biochar and nitrification inhibitor incorporation on global
      warming potential (GWP) of a vegetable field were studied using the static
      chamber and gas chromatography method. Compared with the treatments without
      biochar addition, the annual GWP of N2O and CH4 and vegetable yield were
      increased by 8.7%-12.4% and 16.1%-52.5%, respectively, whereas the greenhouse gas
      intensity (GHGI) were decreased by 5.4%-28.7% following biochar amendment.
      Nitrification inhibitor significantly reduced the N2O emission while had little
      influence on CH4 emission, decreased GWP by 17.5%-20.6%, increased vegetable
      yield by 21.2%-40.1%, and decreased the GHGI significantly. The combined
      application of biochar and nitrification inhibitor significantly increased both
      vegetable yield and GWP, but to a greater extent for vegetable yield. Therefore,
      nitrification inhibitor incorporation could be served as an appropriate practice
      for increasing vegetable yield and mitigating GHG emissions in vegetable field.

PMID- 25757319
TI  - [Bahaviour of Solenopsis invicta workers to protect pupae from infection by
      Metarhizium anisopliae].
AB  - Previous studies have focused on how ants deal with workers infected by pathogens
      but how pupae are protected from infection by fungi is not well understood. The
      behavioral mechanisms adopted by Solenopsis invicta (red imported fire ants,
      RIFA) adult workers to protect pupae against Metarhizium anisopliae infection
      were studied. We observed the behavioral changes of M. anisopliae infected adult
      workers in the brood chamber as well as the behavioral changes of healthy workers
      to fungus exposed pupae. The time of fungus infected workers spent in the pupal
      chamber reduced significantly from 103.4 s on the first day to 38.5 s on the
      third day. Moreover, the percentage of time spending on brood care in the pupal
      chamber reduced significantly from 13.6% on the first day to 3.5% on the third
      day. When pupae were infected by M. anisopliae, workers performed 5.3 times more
      grooming to fungus exposed pupae than controls, and the duration of each grooming
      bout to fungus exposed pupae was 5.2 times longer than controls. Grooming did
      remove many conidia on the surface of fungus exposed pupae. The mean numbers of
      conidia on the surface of pupae were 103.1, 51.6 and 31.3 when no workers, two
      workers and ten workers accompanied a pupa, respectively. The presence of workers
      resulted in a lower germination rate of conidia on the surface of pupae. The mean
      germination rates of conidia after 20 h of inoculation on the surface of pupae
      were 95.1%, 80.4% and 59.9%, in the treatments with no worker, two workers and
      ten workers respectively. There was a positive correlation between the emergence
      rate of pupae and the number of accompanying workers. RIFA protect their pupae
      from infection by M. anisopliae through social be- haviors which enable the
      sustainable development of their population.

PMID- 25757320
TI  - [Ovipositional preference of Grapholitha molesta].
AB  - In order to gain better understanding of the oviposition preference of
      Grapholitha molesta, we studied the ovipositional preference on different host
      fruit leaves, different parts of peach bran- ches and different varieties of
      peach in simulated outdoor conditions. The adult ovipositional preference on the
      host fruit leaves was in descending order, i. e. peach > cherry > apple > plum >
      pear > crabapple > apricot, and 33.5% of eggs were laid on the peach leaves with
      the average number of egg on one peach leaf being 8.3. There were differences in
      egg distribution on both sides of the leaves in different hosts. The number of
      egg laid on the positive surface was more than on the reverse surface of apple
      and crabapple leaves, and vice versus for peach, plum, pear and apricot leaves,
      and 3.3 times more eggs were laid on the reverse surface of peach leaves than on
      the positive surface. The egg distribution had no significant difference on both
      sides of cherry leaves. The adult ovipositional preference on peach branches was
      in descending order of leaf > stipule > petiole > branch. The leaves were the
      major ovipositonal places with 88.7% of total eggs on. 72.5% of eggs were laid on
      the 10 leaves near the top unexpanded leaflets, and the maximum number was on the
      3rd leaf accounting for 9.3%, while only 1.1% of eggs were laid on the peach
      leaves after 25th. The ovipositional preference on different peach fruits was in
      descending order of nectarine > flat peach > prunus persica. The density and
      characteristics of the hair on host fruits and leaves were the primary factors
      affecting the ovipositional preference.

PMID- 25757321
TI  - [Simulation of urban expansion based on SLEUTH model in Fuxin City, Northeast
      China].
AB  - Urban expansion was simulated by SLEUTH model based on the data of Fuxin City,
      Northeast China in 1997-2013. The optimal parameters of urban expansion were
      obtained from SLEUTH model calibration, with the diffusion coefficient as 6,
      breed coefficient as 64, spread coefficient as 44, slope resistance as 52 and
      road gravity as 90. Urban growth types in Fuxin mainly belonged to new center
      growth and edge growth, i.e., the further expansion of new and old urban centers.
      Urban expansion was greatly influenced by roads. Fuxin, as a resource-exhausted
      city, suffered from the natural disasters, such as landslides, subsidence, and so
      on. The slope resistance of urban expansion was large in the development of urban
      land. From the perspective of urban scale, road gravity in smaller city was
      greater than in larger city. The urban expansion in smaller city was more
      inclined to the new center growth. The locations of enterprises and new
      development zones were more interested in the area of good transport facilities.
      Meanwhile, they were inclined to new center growth. Urban expansions were
      simulated based on optimal parameters of SLEUTH model. The simulated result of
      edge growth was better than the simulated result of new spreading center growth,
      because new spreading center growth was susceptible to policymaking, and cellular
      influence was little. The simulated accuracy of urban land in 2001, 2006, 2010
      and 2013 was high.

PMID- 25757322
TI  - [Population dynamics of ground carabid beetles and spiders in a wheat field along
      the wheat-alfalfa interface and their response to alfalfa mowing].
AB  - Taking the wheat-alfalfa and wheat-wheat interfaces as model systems, sampling
      points were set by the method of pitfall trapping in the wheat field at the
      distances of 3 m, 6 m, 9 m, 12 m, 15 m, 18 m, 21 m, 24 m, and 27 m from the
      interface. The species composition and abundance of ground carabid beetles and
      spiders captured in pitfalls were investigated. The results showed that, to some
      extent there was an edge effect on species diversity and abundance of ground
      carabid beetles and spiders along the two interfaces. A marked edge effect was
      observed between 15 m and 18 m along the alfalfa-wheat interface, while no edge
      effect was found at a distance over 20 m. The edge effect along the wheat-wheat
      interface was weaker in comparison to the alfalfa-wheat interface. Alfalfa mowing
      resulted in the migration of a large number of ground carabid beetles and spiders
      to the adjacent wheat filed. During ten days since mowing, both species and
      abundance of ground carabid beetles and spiders increased in wheat filed within
      the distance of 20 m along the alfalfa-wheat interface. The spatial distribution
      of species diversity of ground beetles and spiders, together with the population
      abundance of the dominant Chlaenius pallipes and Pardosa astrigera, were
      depicted, which could directly indicate the migrating process of natural enemy
      from alfalfa to wheat field.

PMID- 25757323
TI  - [Influences of petroleum hydrocarbons on accumulation of cadmium and induction of
      metallothionein in the polychaete Perinereis aibuhitensis].
AB  - Ragworm (Polychaeta) is an ecologically important species in intertidal mudflats
      and estuaries and is recognized as a sentinel species for environmental
      monitoring. In the intertidal belt of China, the ragworm Perinereis aibuhitensis
      is frequently exposed to various toxicants including cadmium (Cd) and petroleum
      hydrocarbons (PHCs). The present study investigated the influence of PHCs on
      accumulation of Cd and the induction of metallothionein (MT) in P. aibuhitensis
      by means of chronic microcosm experiment in which the ragworms were exposed to Cd
      or combinations of Cd and PHCs. The accumulation of Cd in P. aibuhitensis
      increased significantly with the Cd exposure concentration when exposed to Cd
      alone. Further, the bioconcentration factors (BCFs) for Cd in P. aibuhitensis
      increased with the duration of exposure. The addition of PHCs in Cd exposure
      solutions significantly increased the accumulation of Cd in P. aibuhitensis,
      compared with the control. Exposure to Cd induced the expression of MT, and the
      expression increased with the concen- tration up to 180 mg . kg(-1) DM Cd at
      which point the level of induction did not increase. PHCs without Cd did not
      significantly induce MT in P. aibuhitensis, but the addition of PHCs with Cd did
      influence the induction of MT compared to Cd without PHCs. Results indicated that
      PHCs could modulate the expression of MT during co-exposure with Cd. The
      potential substances other than metals influencing the interpretation of MT
      expression in wild P. aibuhitensis must be recognized when MT is used as a
      monitoring index.

PMID- 25757324
TI  - [Correlation between atmospheric PM2.5 concentration and meteorological factors
      during summer and autumn in Beijing, China].
AB  - Based on the monitoring data from 1st July to 31th October, 2008 and 2009 at the
      Beijing urban ecosystem research station, correlations between PM2.5
      concentration and 6 meteorological factors were analyzed, including temperature,
      relative humidity, wind speed, vapour pressure, atmospheric pressure and wind
      direction. Main results showed that the dynamics of PM2.5 concentration displayed
      an obvious fluctuation cycle every 6 weeks, while few changes happened within one
      week. The highest variation in weekly average of PM2.5 concentration happened
      during the third 6 weeks, followed by the first 6 weeks, and the lowest variation
      occurred in the second 6 weeks. Correlation analysis suggested that the weekly
      average of PM2.5 concentration was significantly correlated with all the 6
      meteorological factors, and its correlation with the vapour pressure was the
      greatest. Results presented in this study confirmed that the weekly average of
      PM2.5 concentration between Ju- ly and August in Beijing could be estimated by
      the vapour pressure. The research would benefit the analysis and regulation of
      the pollution source of PM2.5 in Beijing.

PMID- 25757325
TI  - [Evaluation of urban human settlement quality in Ningxia based on AHP and the
      entropy method].
AB  - As one of the key indicators of the urbanization and the sustainable development
      of cities, urban human settlement quality has been a hot issue. In this paper, an
      evaluation system containing indicators related to four aspects (ecological,
      social, humanities and economic environments) was established to assess the urban
      human settlement quality in five main cities in Ningxia Hui Autonomous Region,
      Northwest China. After calculating each indicator' s weight in the evaluation
      system through AHP and the entropy method, the quality of urban human settlement
      was analyzed. Results showed that Yinchuan had a score of 0. 85 for the quality
      of human settlement, Shizuishan 0.62, Wuzhong 0.43, Zhongwei 0.33, and Guyuan
      0.32, respectively. Shizuishan got the highest score in the eco-environment
      aspect, and Yinchuan had the highest scores for social, humanities and economic
      environments. Zhongwei and Guyuan had relatively low scores in all the four urban
      human settlement aspects. Coordination analysis showed that internal coordination
      was moderate for Yinchuan (0.79) and Shizuishan (0.72), and relatively good for
      the other cities. However, coordination was relatively poor among the five
      cities, especially in social environment (0.48). These results suggested that an
      unsatisfied situation existed in terms of the urban human settlement quality in
      Ningxia, and that corresponding measures should be taken to accelerate the
      development of vulnerable indicators, so as to coordinate all the urban human
      settlement aspects within and among cities.

PMID- 25757326
TI  - [WTP guidance technology: a comparison of payment card, single-bounded and double
      bounded dichotomous formats for evaluating non-use values of Sanjiang Plain
      ecotourism water resources].
AB  - Contingent valuation method (CVM) is the most widespread method to assess
      resources and value of environmental goods and services. The guidance technology
      of willingness to pay (WTP) is an important means of CVM. Therefore, the study on
      the WTP guidance technology is an important approach to improve the reliability
      and validity of CVM. This article conducted comprehensive evaluation on non-use
      value of eco-tourism water resources in Sanjiang Plain by using payment card,
      single-bound dichotomous choice and double-bound dichotomous choice. Results
      showed that the socio-economic attributes were consistent with the willingness to
      pay in the three formats, and the tender value, age, educational level, annual
      income and the concern level had significant effect on the willingness to pay,
      while gender and job did not have significant influence. The WTP value was 112.46
      yuan per capita with the payment card, 136.15 with the single-bound dichotomous
      choice, and 168.74 with the double-bound dichotomous choice. Comprehensive
      consideration of the nature of the investigation, investigation costs and
      statistical techniques, the result of double-bound dichotomous choice (47.86 x
      10(8) yuan . a(-1)) was best in accordance with the reality, and could be used as
      non-use value of eco-tourism water resources in Sanjiang Plain. The format of
      questionnaire was very important to improve its validity, and made a great
      influence on the WTP.

PMID- 25757327
TI  - [Progress and prospects on evaluation of ecological restoration: a review of the
      5th World Conference on Ecological Restoration].
AB  - The 5th World Conference on Ecological Restoration was held in Madison,
      Wisconsin, USA on October 6-11, 2013. About 1200 delegates from more than 50
      countries attended the conference, and discussed the latest developments in
      different thematic areas of ecological restoration. Discussions on evaluation of
      ecological restoration were mainly from three aspects: The construction for
      evaluation indicator system of ecological restoration; the evaluation methods of
      ecological restoration; monitoring and dynamic evaluation of ecological
      restoration. The meeting stressed the importance of evaluation in the process of
      ecological restoration and concerned the challenges in evaluation of ecological
      restoration. The conference had the following enlightenments for China' s
      research on evaluation of ecological restoration: 1) Strengthening the
      construction of comprehensive evaluation indicators system and focusing on the
      multi-participation in the evaluation process. 2) Paying more attentions on scale
      effect and scale transformation in the evaluation process of ecological
      restoration. 3) Expanding the application of 3S technology in assessing the
      success of ecological restoration and promoting the dynamic monitoring of
      ecological restoration. 4) Carrying out international exchanges and cooperation
      actively, and promoting China's international influence in ecological restoration
      research.

PMID- 25757328
TI  - [Environmental behavior of graphene and its effect on the transport and fate of
      pollutants in environment].
AB  - Graphene is one of the most popular research topics in carbon nanomaterials.
      Because of its special physical and chemical properties, graphene will have wide
      applications. As the production and application amount is increasing, graphene
      will be inevitably released to the environment, resulting in risks of ecological
      environment and human health. It is of very vital significance for evaluating
      environmental risks of graphene scientifically and objectively to understand its
      environmental behavior and fate and explore its effect on the environmental
      behaviors of pollutants. This paper reviewed the environmental behavior of
      graphene, such as colloid properties and its stability in the aqueous environment
      and its transport through porous media. Additionally, the paper reviewed the
      effect of graphene on the transport and fate of pollutants. The interactions
      between graphene and heavy metals or organic compounds were especially discussed.
      Important topics should be explored including sorption mechanisms, interactions
      between graphene and soil components, influence of graphene on the transport and
      bioavailability of pollutants in environment, as well as approaches to
      quantifying graphene. The review might identify potential new ideas for further
      research in applications of graphene.

PMID- 25757329
TI  - [Research advances in eco-toxicological diagnosis of soil pollution].
AB  - Soil eco-toxicology provides a theoretical basis for ecological risk assessment
      of contaminated soils and soil pollution control. Research on eco-toxicological
      effects and molecular mechanisms of toxic substances in soil environment is the
      central content of the soil eco-toxicology. Eco-toxicological diagnosis not only
      gathers all the information of soil pollution, but also provides the overall
      toxic effects of soil. Therefore, research on the eco-toxicological diagnosis of
      soil pollution has important theoretical and practical significance. Based on the
      research of eco-toxicological diagnosis of soil pollution, this paper introduced
      some common toxicological methods and indicators, with the advantages and
      disadvantages of various methods discussed. However, conventional biomarkers can
      only indicate the class of stress, but fail to explain the molecular mechanism of
      damage or response happened. Biomarkers and molecular diagnostic techniques,
      which are used to evaluate toxicity of contaminated soil, can explore deeply
      detoxification mechanisms of organisms under exogenous stress. In this paper,
      these biomarkers and techniques were introduced systematically, and the future
      research trends were prospected.

PMID- 25757331
TI  - [Review on the feeding ecology and migration patterns of sharks using stable
      isotopes].
AB  - With the rapidly increasing use of stable isotope analysis (SIA) in ecology, it
      becomes a powerful tool and complement to traditional methods for investigating
      the trophic ecology of animals. Sharks play a keystone role in marine food webs
      as the apex predators and are recently becoming the frontier topic of food web
      studies and marine conservation because of their unique characteristics of
      evolution. Recently, SIA has recently been applied to trophic ecology studies of
      shark species. Here, we reviewed the current applications of SIA in shark
      species, focusing on available tissues for analyzing, standardized analytical
      approaches, diet-tissue discrimination factors, diet shift investigation,
      migration patterns predictions and niche-width analyses, with the aim of getting
      better understanding of stable-isotope dynamics in shark biology and ecology
      research.

PMID- 25757330
TI  - [Effects of agricultural activities and transgenic crops on agricultural
      biodiversity].
AB  - Agricultural biodiversity is a key part of the ecosystem biodiversity, but it
      receives little concern. The monoculture, environmental pollution and habitat
      fragmentation caused by agricultural activities have threatened agricultural
      biodiversity over the past 50 years. To optimize agricultural management measures
      for crop production and environmental protection, we reviewed the effects of
      agricultural activities, including cultivation patterns, plastic mulching,
      chemical additions and the cultivation of transgenic crops, on agricultural
      biodiversity. The results showed that chemical pesticides and fertilizers had the
      most serious influence and the effects of transgenic crops varied with other
      factors like the specific transgene inserted in crops. The environmental risk of
      transgenic crops should be assessed widely through case-by-case methods,
      particularly its potential impacts on agricultural biodiversity. It is important
      to consider the protection of agricultural biodiversity before taking certain
      agricultural practices, which could improve agricultural production and
      simultaneously reduce the environmental impacts.

PMID- 25757332
TI  - [Solid-State and membrane-surface liquid cultures of micromycetes: specific
      features of their development and enzyme production (a review)].
AB  - Specific features in the development of micromycetes, typical mechanisms of their
      enzyme production, and conditions providing for an increase in enzyme secretion
      by the microscopic fungi in solid-state (on natural substrates and inert
      carriers) and membrane-surface liquid cultures are considered. The prospects and
      advantages of these fermentation methods for the production of extracellular
      enzymes are discussed and compared with submerged cultures.

PMID- 25757333
TI  - [Extracellular lectins from saprophytic strains of bacteria of the genus Bacillus
      (review)].
AB  - The present review summarizes both the authors' own and other researchers'
      reports concerning the synthesis and properties of sialic acid-specific
      extracellular lectins from saprophytic bacteria of the genus Bacillus. Bacilli of
      this genus isolated from different ecological niches differ with regard to the
      ability to synthesize lectins. The biphasic temporal pattern of lectin synthesis
      in culture and the effect of cultivation conditions on lectin production have
      been demonstrated. The advantages of the technological procedure used for the
      isolation and purification of these biopolymers have been characterized.
      Specificity towards sialic acid, which is characteristic only of a small number
      of lectins from bacilli and underlies a wide range of biological effects of these
      proteins, receives particular attention. Adaptation mechanisms involving lectins-
      carbohydrate-recognizing proteins--are suggested to have developed in saprophytic
      bacilli to ensure the survival of these organisms in a constantly changing
      environment.

PMID- 25757334
TI  - [Application of repair enzymes to improve the quality of degraded DNA templates
      for PCR amplification].
AB  - PCR amplification of severely degraded DNA, including ancient DNA, forensic
      samples, and preparations from deeply processed foodstuffs, is a serious problem.
      Living organisms have a set of enzymes to repair lesions in their DNA. In this
      work, we have developed and characterized model systems of degraded high
      molecular-weight DNA with a predominance of different types of damage. It was
      shown that depurination and oxidation of the model plasmid DNA template led to a
      decrease in the PCR efficiency. A set of enzymes performing a full cycle of
      excision repair of some lesions was determined. The treatment of model-damaged
      substrates with this set of enzymes resulted in an increased PCR product yield as
      compared with that of the unrepaired samples.

PMID- 25757336
TI  - [Comparative characteristics of biosynthesis of polyhydroxybutyrate from methanol
      by Methylobacteria extorquens G10 and Methyloligella halotolerans C2].
AB  - The biosynthesis of polyhydroxybutyrate by Methylobacteria extorquens G10 and
      Methyloligella halotolerans C2 via the serine pathway of C1 metabolism was
      comparatively studied. Nitrogen limitation stimulated synthesis of the biopolymer
      in both cultures. It was shown that, despite the similarity of the pathways of
      methanol metabolism and those of polyhydroxybutyrate biosynthesis, the
      methylobacteria synthesized polymers of different molecular weights. In the case
      of M. extorquens G10, an increase in the content of the residual nitrogen in the
      culture medium was found to result in a reduction of the molecular weight of the
      polymer from 250 to 85 kDa, whereas M. halotolerans C2 synthesized a polymer of
      high molecular weight (approximately 3000 kDa) regardless of the residual content
      of the nitrogen source. It was established that the examined methylobacteria can
      utilize not only pure methanol but also a crude one, a feature that made it
      possible to significantly reduce the cost of the resulting polyhydroxybutyrate.

PMID- 25757335
TI  - Molecular mutagenesis at Tyr-101 of the amylomaltase transcribed from a gene
      isolated from soil DNA.
AB  - The wild-type (WT) amylomaltase gene was directly isolated from soil DNA and
      cloned into a pET19b vector to express in E. coli BL21(DE3). The ORF of this gene
      consisted of 1,572 bp, encoding an enzyme of 523 amino acids. Though showing 99%
      sequence identity to amylomaltse from Thermus thermophilus ATCC 33923, this
      enzyme is unique in its alkaline optimum pH. In order to alter amylomaltase with
      less coupling or hydrolytic activity to enhance cycloamylose (CA) formation
      through cyclization reaction, site-directed mutagenesis of the second glucan
      binding site involving in CA production was performed at Tyr-101. The result
      revealed that the mutated Y101S enzyme showed a small increase in cyclization
      activity while significantly decreased disproportionation, coupling and
      hydrolytic activities. Mutation also resulted in the change in substrate
      specificity for disproportionation reaction. The WT enzyme preferred maltotriose,
      while the activity of mutated enzyme was the highest with maltopentaose
      substrate. Product analysis by HPAEC-PAD demonstrated that the main CAs of the WT
      amylomaltase were CA29-CA37. Y101S mutation did not change the product pattern,
      however, the amount of CAs formed by the mutated enzyme tended to increase
      especially at long incubation time.

PMID- 25757337
TI  - [Genetic modification of Methylobacterium extorquens G10 producer strain of
      polyhydroxybutyrate].
AB  - The effect of the increased copy number of polyhydroxybutyrate (PHB) biosynthesis
      genes in pink-pigmented methylobacterium Methylobacterium extorquens G10 on
      properties of the biopolymer was studied. The activity of poly-3-hydroxybutyril
      synthase (PHB-synthase) was shown to increase and the molecular weight of
      synthesized PHB decreases twofold (150 --> 79 kDa) after insertion of extra
      copies of phaC and phaCAB genes into cells of the producer strain, whereas the
      physicochemical properties of the plastic changed insignificantly. White mutant
      M. extorquens G10-W with disrupted synthesis of the carotenoid pigment (defect by
      the crtI gene, which codes for phytoene desaturase) was established to have the
      same rate of growth and level of PHB accumulation as the initial strain G10. The
      G10-W strain is a promising producer of PHB, with decreased expenses for
      purification and PHB biosynthesis.

PMID- 25757338
TI  - [Adaptation of coimmobilized Rhodococcus cells to oil hydrocarbons in a column
      bioreactor].
AB  - The possible adaptation of the association of Rhodococcus ruber and Rhodococcus
      opacus strains immobilized on modified sawdust to oil hydrocarbons in a column
      bioreactor was investigated. In the bioreactor, the bacterial population showed
      higher hydrocarbon and antibiotic resistance accompanied by the changes in cell
      surface properties (hydrophobicity, electrokinetic potential) and in the content
      of cellular lipids and biosurfactants. The possibility of using adapted
      Rhodococcus strains for the purification of oil-polluted water in the bioreactor
      was demonstrated.

PMID- 25757339
TI  - [Microbial potential for cleaning the oiled iron scale].
AB  - The possibility of using microorganisms to clean oiled iron scale of
      metallurgical production was investigated with the goal of recuperation. A stable
      microbial association growing on mineral oil as the sole carbon source was
      isolated from a sample from oiled iron scale taken directly from a metallurgical
      plant. For microbial cultures isolated from this association, the taxonomic
      position, as well as their morphological and cultural characteristics, were
      determined. The microorganisms belonged to the genera Luteimonas, Alcanivorax,
      Flavobacterium, and Pseudomonas. Microbial associations oxidizing mineral oil
      were found to contain some microorganisms incapable of its utilization, which
      stimulated the hydrocarbon-oxidizing microflora. Application of the isolates, as
      well as of the strains from microbial collections, resulted in a 58% decrease in
      residual oil content in treated samples of the oiled iron scale.

PMID- 25757340
TI  - Biodegradation of feather wastes and the purification and characterization of a
      concomitant keratinase from Paecilomyces lilacinus.
AB  - Paecilomyces lilacinus strain PL-HN-16 was found to have the ability to degrade
      feathers. During the degradation process, the broth initially turned as sticky as
      gelatin and then turned into fluid that means the feathers can be hydrolyzed
      completely. Keratinolytic protein (Ker) of aforementioned strain was purified
      using ammonium sulphate precipitation, HiTrap Butyl FF chromatography and
      Sephacryl S-200 gel filtration. The Ker of P. lilacinus PL-HN-16 had molecular
      mass of 33 kDa, the optimum pH 8.0 and temperature optimum at 40 degrees C. It
      used the soluble keratin as substrate. The enzyme showed high activity and
      stability over a wide range of pH (6.0 to 10.0) and temperature (300C to 600C)
      values but was completely inhibited by PMSF. Ker of P. lilacinus PL-HN-16
      exhibited stability toward SDS. These promising properties make the enzyme a
      potential candidate for future applications in biotechnological processes as
      keratin hydrolysis and dehairing during leather processing.

PMID- 25757341
TI  - [Influence of lignin and oxygen on the growth and the lipid formation of the
      fungus Lentinus tigrinus].
AB  - During cultivation of the filamentous fungus Lentinus tigrinus on a medium
      containing lignin, a high oxygen content stimulated the growth of the fungus and
      contributed to the yield of lipids. A high content of phosphatidic acid and a
      reduction in the level of phosphatidylethanolamine and phosphatidylserine were
      first detected in the composition of phospholipids. Changes in the composition of
      neutral lipids, such as variation in the ratio of esterified and free sterols,
      have occurred; thus, the amount of sterol esters reduced simultaneously with a
      decrease in the content of free fatty acids. Based on the obtained results, the
      possible role of phosphatidic acid as a second messenger in the process of the
      consumption of lignin by the fungus Lentinus tigrinus is discussed.

PMID- 25757342
TI  - Erythritol production with minimum by-product using Candida magnoliae mutant.
AB  - In order to enhance erythritol production, mutants of Candida magnoliae DSM70638
      were generated by ultraviolet and chemical mutagenesis. Erythritol productivity
      of samples was analyzed by TLC and HPLC with the refractive index detector. One
      of the mutants named mutant 12-2 gave a 2.4-fold increase in erythritol (20.32
      g/L) and a 5.5-fold decrease in glycerol production compared to the wild strain.
      A sequence-based map of erythrose reductase gene in this mutant showed a
      replacement of the A321 by G321 that did not cause any amino acid exchange in
      protein structure. Therefore, the reason of higher erythritol production in C.
      magnoliae mutant 12-2 is probably the increase in expression of the open reading
      frame gene. This study revealed that a mutation or minor change in the sequence
      of genes involved in a production pathway can lead to a significant increase in
      protein translation.

PMID- 25757343
TI  - Gas chromatography-mass spectrometry characterisation of the anti-Listeria
      components of Garcinia kola seeds.
AB  - Adsorption chromatography was used to separate the bioactive constituents of the
      crude n-hexane extract of Garcinia kola seeds. The silica gel 60 column fractions
      were eluted using the solvent combination of benzene: ethanol : ammonium
      hydroxide (BEA) in the ratio combination of 36 : 4 : 0.4 v/v. The fractions were
      tested for anti-Listeria activities by determining their MIC50, MIC90 or MIC
      against 4 Listeria isolates. The fractions were labelled BEA1 to BEA5 and 3 out
      of the 5 fractions eluted were active against the test Listeria species with
      MIC's ranging from MIC 0.57 mg/mL to MIC50 0.625 mg/mL. The most active
      fractions, BEA2 and BEA3, were subjected to gas chromatography coupled to mass
      spectrometry (GC-MS) to identify their composition. Fraction BEA2 constituted of
      18 compounds mostly sterols and the BEA3 fraction contained 27 compounds with the
      most abundant compounds being fatty acids derivatives. The BEA2 fraction's
      interactions with antibiotics proved to be 100% synergistic with ciprofloxacin
      and ampicillin whilst it exhibited 50% additivity and 50% synergism with
      penicillin G. However, all the interactions of the BEA2 fraction with each of the
      conventional antibiotics used were synergistic against the human listeriosis
      causative bacteria Listeria monocytogenes.

PMID- 25757344
TI  - [Genetic and molecular principles for the selection of Pseudomonas and
      Staphylococcus therapeutic bacteriophages].
AB  - The content of empirically selected bacteriophage mixtures, produced by Microgen
      for the prevention and treatment of staphylococcal and pseudomonade infections,
      was investigated by negative stain electron microscopy. The main population of
      phages was shown to belong to the groups suitable for therapeutic purposes based
      on bioinformatics analysis of known genomes of Pseudomonas and Staphylococcus
      phages. However, the phage morphology studies did not always reveal the exact
      correspondence of the phage to the exact group. Therefore, we suggest group
      genotyping of the therapeutic bacteriophages on thebasis of genetic conservative
      locus.

PMID- 25757345
TI  - [Distribution of intraductal carcinoma of the prostate and associated lesions in
      the cancer foci on radical prostatectomy specimens].
AB  - OBJECTIVE: The distribution of intraductal carcinoma of the prostate (IDC-P) and
      other intraductal lesions associated with IDC-P was evaluated in the cancer foci
      on radical prostatectomy specimens. MATERIALS AND METHODS: We reviewed slide in
      412 cases treated by radical prostatectomy without neoadjuvant therapy. Mapping
      study was performed with regard to IDC-P, other intraductal lesions associated
      with IDC-P and invasive carcinoma. RESULTS: We identified 98 cases (23.8%) and
      102 cancer foci associated with IDC-P. In these all cancer foci, IDC-P was
      associated with invasive carcinoma and other intraductal neoplastic lesions with
      tufting, micropapillary and loose cribriform patterns were contiguous and admixed
      with IDC-P in 83 cancer foci (81.4%). There were lesions with invasive carcinoma
      around the IDC-P in 95 cancer foci (93.1%) and lesions without invasive carcinoma
      around IDC-P in 66 foci (64.7%). The latter lesions existed in the marginal areas
      of the cancer foci in 63 (61.8%) and in the central areas of the cancer foci in
      14 (13.7%). In 5 cancer foci (4.9%), volume of IDC-P was larger than that of
      invasive carcinoma. CONCLUSIONS: The distribution of IDC-P with dense cribriform
      and solid patterns varied in cancer foci, and intraductal lesions with tufting,
      micropapillary and loose cribriform patterns were frequently seen in area
      contiguous and admixed with IDC-P. The latter lesion may be low grade morphology
      of IDC-P, although the lesions could not be distinguished from high grade
      prostatic intraepithelial neoplasia.

PMID- 25757347
TI  - [Interstitial cystitis in urology clinic: current status and problems].
AB  - PURPOSE: We examined the complications in the diagnosis and treatment of
      interstitial cystitis in daily clinical practice. MATERIALS AND METHODS: The
      study included 82 patients who were suspected of having interstitial cystitis at
      our hospital from March 2002 to April 2013. All hydrodistention procedures were
      performed with the aid of an anesthesiologist, as recommended by the Ministry of
      Health, Labour, and Welfare since April 2010. RESULTS: Of the 82, 20 patients
      were male and 62 were female, (mean age at diagnosis 53 years.) Six of the
      suspected cases did not have interstitial cystitis. Of the 67 patients diagnosed
      with interstitial cystitis during hydrodistention, 29 (43%) did not experience
      pain. The time taken to diagnose these asymptomatic patients was longer than that
      taken for those who experienced pain. Twenty-eight patients (42%) discontinued
      treatment because it was ineffective. CONCLUSION: Interstitial cystitis has been
      widely recognized, but general physicians are unable to provide a diagnosis and
      suggest aggressive treatment because of difficulty associated in the treatment
      and diagnosis. To resolve these issues, physicians should be keep in mind that
      interstitial cystitis involves a hypersensitive bladder, and that some patients
      may not experience pain. Further, knowledge about Hunner's ulcer is essential. We
      believe that the most important points are improving health insurance about
      facility criteria of hydrodistention, and evaluating behavioral modification and
      dietary manipulation.

PMID- 25757346
TI  - [Clinical study of long-term docetaxel based chemotherapy treatment for patients
      with castration-resistant prostate cancer].
AB  - PURPOSE: To evaluate long-term continuous administration of docetaxel (DOC), over
      survival rate, PSA level and adverse effects were analyzed, retrospectively. We
      also compared the results of long-term treatment group and short-term treatment
      group. MATERIAL AND METHODS: This study reported that 14 cases of long-term
      continuous administration of DOC consisting of 11 or more cycles among 51
      patients of castration-resistant prostate cancer (CRPC) treated with DOC from
      October 2008 to September 2013 at our institution, retrospectively. Nineteen
      patients who had treated with DOC 10 or less cycles were defined as short-term
      dose group, and both groups were compared. DOC was administered every 3 to 4
      weeks at 60 to 70 mg/m2, and was treated with prednisolone at 10 mg/day as a
      general. RESULTS: The median number of treatment cycles was 15. Thirteen cases
      showed a decrease in PSA levels and 10 cases showed a decrease in PSA levels of
      50% or more, the 1-year survival rate of long-term dose and short-term dose group
      were 100% and 16%. Adverse effects of grade 3 or lower consisted of
      leukocytopenia in 85% and thrombocytopenia in 28%, however, grade 4 or higher
      were not observed in long-term dose group. In multivariable analysis of
      parameters, long-term treatment was related to PSA levels at start of treatment
      and ALP levels. CONCLUSION: Forty-two percent of patients who have CRPC at our
      institution undergo long-term DOC based chemotherapy treatment It may be
      suggested that long-term DOC based chemotherapy for some cases contribute to
      extend survival time with no serious adverse events.

PMID- 25757348
TI  - [Study on the treatment of pelvic organ prolapse complicated with uterine myoma].
AB  - OBJECTIVE: We studied the association between uterine myoma and recurrent pelvic
      organ prolapse (POP) after transvaginal mesh (TVM) repair. METHODS: Between June
      2010 and January 2012, 103 female patients (mean age 67.8 years, mean parity 2.3,
      mean body mass index (BMI) 23.7) with POP underwent TVM procedures at our
      hospital. Sixtynine patients were qualified as stage 3 according to the POP
      quantification (POP-Q) system and 34 patients were stage 4. Twenty-six patients
      underwent anterior TVM (A-TVM) and 77 patients underwent anterior and posterior
      TVM (AP-TVM). All patients underwent a physical examination using the POP-Q
      system before and 6 month after surgery. Recurrence of prolapse was defined
      according to the International Continence Society by a measured value >= - 1, as
      most dependent portion of POP stage 2 or greater. One hundred-three patients were
      divided into group with uterine myoma larger than 5 cm in diameter and group
      without uterine myoma. Anatomical outcomes before and after TVM repair were
      compared between two groups. RESULTS: Preoperative Aa value, Ba value and gh
      value in group with uterine myoma were greater than in group without uterine
      myoma. Postoperative Aa value and Ba value in group with uterine myoma were
      greater than in group without uterine myoma, too. Postoperative recurrence of
      prolapse of stage 2 or greater was not found a statistical difference between two
      groups. CONCLUSIONS: The risks of anterior vaginal wall descent seem to be high
      in POP with uterine myoma. Therefore it should be kept in mind on treatment
      choice.

PMID- 25757349
TI  - [Clinical outcomes after combined therapy with dutasteride in patients with
      unsuccessful trial without catheter after treatment with an alpha1-adrenergic
      receptor blocker monotherapy for acute urinary retention caused by prostatic
      hyperplasia].
AB  - OBJECTIVE: The outcome of trial of voiding without catheter in patients treated
      combination therapy with dutasteride and alpha1-adrenergic receptor blocker for
      acute urinary retention caused by benign prostatic hyperplasia was not reported.
      We evaluated the clinical efficacy of combination therapy with dutasteride in
      patients with unsuccessful trial without catheter after treatment with an alpha1
      adrenergic receptor blocker monotherapy for acute urinary retention caused by
      benign prostatic hyperplasia. PATIENTS AND METHODS: Patients with acute urinary
      retention due to prostatic hyperplasia were catheterized and treated alpha1
      adrenergic receptor blocker monotherapy. After two weeks later, patients were put
      on trial without catheter. 52 patients who were unsuccessful trial without
      catheter administered combination therapy with dutasteride and alpha1-adrenergic
      receptor blocker. We use criteria that voiding urine volume over 100 ml and post
      void residual urine volume below 100 ml in deciding whether catheter should be
      removed. RESULTS: 33 (63.5%) men did not require re-catheterization within 7
      months after combination therapy. The successful rate of Performance Status (PS)
      0-1 group was significantly superior to that of PS 2-4 group. CONCLUSIONS: PS 0-1
      men catheterized for AUR can void more successfully after catheter removal than
      PS 2-4 men if treated with combination therapy.

PMID- 25757350
TI  - [Nurse questionnaire survey about the urethral catheterization and clinical
      analysis of iatrogenic urethral injury].
AB  - OBJECTIVE: This study was aimed at determining the status of iatrogenic urethral
      injury associated with insertion of urethral catheters at our hospital. SUBJECTS
      AND METHODS: We studied the data of 32 patients with iatrogenic urethral injury
      at our hospital. We also carried out a questionnaire survey of 150 nurses who
      could be in charge of urethral catheter insertions, and conducted an analysis
      based on the answers obtained from 133 of the 150 nurses (response rate 88.7%).
      RESULTS: The 32 patients included 14 patients with reduced activity of daily
      living (ADL) who required assistance in daily life (44%), 4 patients with spinal
      cord injury (13%), and 4 patients under anesthesia or sedation (13%). Acute
      complications included sepsis in 5 patients (16%) and septic shock in 3 patients
      (9%). Long-term urethral catheterization was indicated in all the patients with
      sepsis. Examination of the responses to the questionnaire showed that while 86%
      of the nurses said "I inject water to fix the balloon after confirming urine
      outflow," 7% answered "I inject water into the balloon even if there is no urine
      outflow"; 46% said "I compress the lower abdomen when there is no urine outflow,"
      6% said "I perform urinary bladder irrigation," and 48% said "I neither compress
      the lower abdomen when there is no urinary flow nor perform urinary bladder
      irrigation". CONCLUSION: Nearly half of the patients with iatrogenic urethral
      injury at our hospital had reduced ADL. In the patients in whom long-term
      catheterization was indicated, urethral injury at the time of regular replacement
      of a catheter was associated with a high likelihood of sepsis occurring as a
      complication. Based on the results of the questionnaire, more than 80% of the
      nurses complied with the rule that water to fix the balloon must be injected only
      after confirming urinary outflow at the time of inserting a urethral catheter.
      However, when there was no urine outflow after insertion of the catheter, there
      were variations in the procedure to handle the situation. In the education of
      nurses, training on the appropriate actions that must be taken in this situation
      appears to be important.

PMID- 25757351
TI  - [Case of juxtaglomerular cell tumor (reninoma) treated with laparoscopic partial
      nephrectomy].
AB  - We report a case of a 22-year-old male with juxtaglomerular cell tumor treated
      with laparoscopic partial nephrectomy. He was referred to our hospital with
      hypertension, high concentration of plasma renin activity (PRA) and renal mass.
      Dynamic enhanced computed tomography showed 17-mm weak contrast-enhancing tumor
      at the upper pole of the left kidney. Renin suppression and stimulation test
      revealed autonomous renin secretion although renal venous sampling failed to show
      significant difference in the PRA between the right and left renal vein. We
      performed laparoscopic left partial nephrectomy. The histological diagnosis was
      juxtaglomerular cell tumor. After the operation, his blood pressure and PRA were
      immediately normalized. Juxtaglomerular cell tumor is an important renal tumor as
      a curable cause of secondary hypertension.

PMID- 25757352
TI  - [Adenocarcinoma arising in an ileum segment of Scheele's ring 50 years after
      cystoplasty].
AB  - A 70 year-old woman visited our hospital complaining of macrohematuria. She had
      undergone augmentation ileocystoplasty for tuberculous bladder atrophy 50 years
      previously. CT and cystoscopy showed tumor at the ileovesical anastomosis. She
      underwent a partial cystectomy. The pathological diagnosis was adenocarcinoma of
      the ileal segment. Recurrence was observed with rapid progression. The patient
      died 8 months after the operation. In Japanese literature, 43 cases of carcinoma
      arising in augumented bladder have been reported. Average period to the diagnosis
      of the cancer from the ileocystoplasty is 33 years. The period of our case was 50
      years, the longest in 43 cases.

PMID- 25757353
TI  - [Prostate cancer of unknown primary origin with multiple lymph nodes metastasis;
      a case report].
AB  - A 62-year-old man were referred our hospital complaining of high prostate
      specific antigen (PSA) value (32.4 ng/ml) in May 2010. Two sets of biopsies
      preformed previously at another hospital had not detected any cancers in the
      prostate. In our hospital, prostate biopsies were performed in July 2010 and
      February 2011, but cancer was not detected in either occasion. In March 2011, his
      PSA increased up to 126.7 ng/ml, CT scan showed the swelling of left
      supraclavicular and para-aortic lymph nodes. Biopsy of the supraclavicular lymph
      node was performed. Pathology revealed poorly differentiated adenocarcinoma with
      positive immunohistochemistry for PSA, which was suggestive of metastatic
      prostate cancer. After 1 year of treatment with androgen deprivation therapy, the
      patient developed castration resistant prostate cancer and have undergone
      chemotherapy with docetaxel.

PMID- 25757354
TI  - [Rhabdomyolysis after radical nephrectomy in the lateral decubitus position:
      report of 2 cases].
AB  - Rhabdomyolysis is a rare perioperative complication, however, potentially lead to
      fatal outcome. We experienced 2 cases of rhabdomyolysis after radical nephrectomy
      and nephroureterectomy in the lateral decubitus position. (Case 1) A 40-years old
      man was seen in our hospital because of asymptomatic grosshematuria. Computed
      tomography revealed right renal pelvic cancer, cT3N0M0. Right radical
      nephroureterectomy, lymph node dissection, partial cystectomy was underwent, and
      the operation was finished without any trouble. At the post-operative day 1,
      serum creatinine level was elevated to the point of 4.2 mg/dl, and serum creatine
      kinase was 1,945 IU/l. Continuous hemodiafiltration (CHDF) was done at intensive
      care unit (ICU), and serum creatinine and creatine kinase level were decreased.
      At the post-operative day 1, urine myoglobin level was prominently elevated
      (2,943.7 ng/ml), so we diagnosed acute renal failure due to rhabdomyolysis. (Case
      2) A 40-years old man was incidentally pointed out of right renal tumor that was
      seen as renal cell carcinoma, cT1aN0M0. Open partial nephrectomy was underwent,
      and there was no trouble during the operation. After recovering from anesthesia,
      the patient felt left thigh pain strongly. Serum creatine kinase was 888 IU/L
      after the operation. At the postoperative day 1, serum creatine kinase level was
      markedly increased (31,138 IU/L). Serum creatinine level was 1.34 mg/dl. Urine
      and serum myoglobin level was prominently elevated (89,000 ng/ml and 8,634 ng/ml,
      respectively). We diagnosed it rhabdomyolysis, and he received large amount of
      fluid intravenously at intensive-care unit. Serum creatine kinase was peak out at
      the post-operative day 3 (20,709 IU/L), and hemodialysis was not performed.

PMID- 25757355
TI  - [Acute renal failure due to obstructive ureteral stone associated with norovirus
      gastroenteritis in an infant with congenital solitary kidney].
AB  - We report a 35 month-old boy with acute renal failure caused by an obstructive
      ureteral stone associated with norovirus gastroenteritis. He visited his family
      physician because of fever, abdominal pain and vomiting. He was diagnosed as
      acute gastroenteritis. The symptoms relieved once, but abdominal pain and
      vomiting recurred two days after the visit and the volume of urine decreased. He
      was diagnosed as norovirus gastoenteritis and acute renal failure which was
      unresponsive to fluid replacement. Ultrasound study of the abdomen showed a
      solitary kidney with mild hydronephrosis. He was then admitted to our hospital.
      He was finally diagnosed as acute postrenal failure due to obstructive ureteral
      stone with left solitary kidney by abdominal computer tomography (CT). We
      performed transurethral catheterization immediately. The creatinine and blood
      urea nitrogen returned to normal level in 2 days. The CT performed on the 28th
      day post operation showed disappearance of the stone after uric alkalization.
      Recently, some cases of postrenal failure due to bilateral obstructive ureteral
      stones, mainly ammonium acid urate stones, associated with viral gastroenteritis
      were reported. As clinical features, they are common in boys three years or
      younger after an episode of rotavirus gastroenteritis with high uric acid
      concentration. By far, the most common cause of acute renal failure in patients
      with severe gastroenteritis is prerenal failure resulting from hypovolemia. But
      postrenal cause due to bilateral obstructive stones should be taken in a
      consideration.

PMID- 25757356
TI  - Do Racial/Ethnic Disparities in Quality and Patient Experience within Medicare
      Plans Generalize across Measures and Racial/Ethnic Groups?
AB  - OBJECTIVE: To examine how similar racial/ethnic disparities in clinical quality
      (Healthcare Effectiveness Data and Information Set [HEDIS]) and patient
      experience (Consumer Assessment of Healthcare Providers and Systems [CAHPS])
      measures are for different measures within Medicare Advantage (MA) plans. DATA
      SOURCES/STUDY SETTING: 5.7 million/492,495 MA beneficiaries with 2008-2009
      HEDIS/CAHPS data. STUDY DESIGN: Binomial (HEDIS) and linear (CAHPS) hierarchical
      mixed models generated contract estimates for HEDIS/CAHPS measures for Hispanics,
      blacks, Asian-Pacific Islanders, and whites. We examine the correlation of within
      plan disparities for HEDIS and CAHPS measures across measures. PRINCIPAL
      FINDINGS: Plans with disparities for a given minority group (vs. whites) for a
      particular measure have a moderate tendency for similar disparities for other
      measures of the same type (mean r = 0.51/.21 and 53/34 percent positive and
      statistically significant for CAHPS/HEDIS). This pattern holds to a lesser extent
      for correlations of CAHPS disparities and HEDIS disparities (mean r =
      0.05/0.14/0.23 and 4.4/5.6/4.4 percent) positive and statistically significant
      for blacks/Hispanics/API. CONCLUSIONS: Similarities in CAHPS and HEDIS
      disparities across measures might reflect common structural factors, such as
      language services or provider incentives, affecting several measures
      simultaneously. Health plan structural changes might reduce disparities across
      multiple measures.

PMID- 25757357
TI  - IR spectrum of the protonated neurotransmitter 2-phenylethylamine: dispersion and
      anharmonicity of the NH3(+)-pi interaction.
AB  - The structure and dynamics of the highly flexible side chain of (protonated)
      phenylethylamino neurotransmitters are essential for their function. The
      geometric, vibrational, and energetic properties of the protonated
      neutrotransmitter 2-phenylethylamine (H(+)PEA) are characterized in the N-H
      stretch range by infrared photodissociation (IRPD) spectroscopy of cold ions
      using rare gas tagging (Rg = Ne and Ar) and anharmonic calculations at the B3LYP
      D3/(aug-)cc-pVTZ level including dispersion corrections. A single folded gauche
      conformer (G) protonated at the basic amino group and stabilized by an
      intramolecular NH(+)-pi interaction is observed. The dispersion-corrected density
      functional theory calculations reveal the important effects of dispersion on the
      cation-pi interaction and the large vibrational anharmonicity of the NH3(+) group
      involved in the NH(+)-pi hydrogen bond. They allow for assigning overtone and
      combination bands and explain anomalous intensities observed in previous IR
      multiple-photon dissociation spectra. Comparison with neutral PEA reveals the
      large effects of protonation on the geometric and electronic structure.

PMID- 25757359
TI  - Letter to the Editor for the article "Osteonecrosis of distal tibia in open
      dislocation fractures of the ankle".

PMID- 25757358
TI  - Expectations among patients and health professionals regarding Web-based
      interventions for depression in primary care: a qualitative study.
AB  - BACKGROUND: One-quarter of the world's population will suffer from depression
      symptoms at some point in their lives. Mental health services in developed
      countries are overburdened. Therefore, cost-effective interventions that provide
      mental health care solutions such as Web-based psychotherapy programs have been
      proposed. OBJECTIVE: The intent of the study was to identify expectations
      regarding Web-based psychotherapy for the treatment of depression in primary care
      among patients and health professionals that might facilitate or hinder its
      effects. METHODS: The expectations of untreated patients and health professionals
      were examined by means of interviews and focus groups. There were 43 participants
      (20 patients with mild and moderate levels of depression, 11 primary care
      physicians, and 12 managers; 22 of them for interviews and 21 for groups). A
      thematic content analysis from the grounded theory for interviews, and an
      analysis of the discursive positions of participants based on the sociological
      model for groups were performed. Interpretations were achieved by agreement
      between three independent analysts. RESULTS: All participants showed a good
      general acceptance of Web-based psychotherapy, appreciating possible advantages
      and improvements. Patients, physicians, and managers shared the same
      conceptualization of their expectations, although highlighting different aspects.
      Patients focused on the need for individualized and personalized interaction,
      while professionals highlighted the need for the standardization of the program.
      Physicians were concerned with extra workload, while managers were worried about
      optimizing cost-effectiveness. CONCLUSIONS: Expectations of the different
      participants can conflict with each other. Finding a balanced position among them
      is needed if we are to harmoniously implement effective Web-based interventions
      for depression in routine clinical practice.

PMID- 25757361
TI  - Roles of syndecan-4 and relative kinases in dorsal root ganglion neuron adhesion
      and mechanotransduction.
AB  - Mechanical stimuli elicit a biological response and initiate complex
      physiological processes, including neural feedback schemes associated with senses
      such as pain, vibration, touch, and hearing. The syndecans (SDCs), a group of
      adhesion receptors, can modulate adhesion and organize the extracellular matrix
      (ECM). In this study, we cultured dorsal root ganglia (DRG) on controlled
      polydimethylsiloxane (PDMS) substrates coated with poly-l-lysine (poly) or
      fibronectin (FN) to investigate cell adhesion and mechanotransduction mechanisms
      by mechanical stretching on PDMS using DRG neurons. Our results demonstrated that
      neuronal density, neurite length, and neurite branching were lower in the PDMS
      group and could be further reversed through activating SDC-4 by FN. The
      expression of the SDC-4 pathway decreased but with increased pPKCalpha in the
      PDMS-poly group. After mechanical stretching, pPKCalpha-FAKpTyr397-pERK1/2
      expression was increased in both poly- and FN-coated PDMS. These results indicate
      that SDC4-pPKCalpha-FAKpTyr397-pERK1/2 may play a crucial role in DRG adhesion
      and mechanotransduction.

PMID- 25757362
TI  - Interleukin-10 levels in rat models of nerve damage and neuropathic pain.
AB  - Interleukin-10 (IL-10) is an anti-inflammatory cytokine that has been shown to
      play a role in inflammatory and autoimmune disorders as well as in neuropathic
      pain conditions. The objective of the present study was to assess the levels of
      IL-10 in rat's dorsal root ganglion (DRG) and the sciatic nerve following four
      different forms of sciatic nerve injury. The models used to induce the injury
      included two models of partial nerve injury: partial sciatic ligation (PSL) and
      chronic constriction injury (CCI), a model of complete sciatic transection (CST)
      and a model of perineural inflammation with minimal nerve damage (neuritis).
      Withdrawal responses for mechanical stimulus and withdrawal latency for thermal
      stimulation were used to measure mechanical and thermal hyperalgesia,
      respectively, and duration of the nociceptive withdrawal reflex to mechanical
      stimulus was used to measure mechanical hyperalgesia. The affected and contra
      lateral nerves and the affected side DRG IL-10 levels were assessed by the means
      of enzyme-linked immunosorbent assay (ELISA), 3 and 8 days following the
      procedure and were compared to naive rats' IL-10 levels. The rats exposed to CCI
      and neuritis developed significant mechanical and thermal hyperalgesia as well as
      mechanical hyperalgesia 3 and 8 days following the surgical procedure. Rats
      exposed to CST did not respond to mechanical stimulation and developed thermal
      hypoalgesia 3 and 8 days after the surgery. The DRG IL-10 levels were
      significantly reduced 3 and 8 days following CCI and PSL, significantly increased
      3 and 8 days following CST, and remained unchanged following neuritis. The
      sciatic nerve IL-10 levels reduced significantly in both injured and contra
      lateral nerves 3 and 8 days following CCI and PSL, elevated significantly in the
      injured but not in the contra-lateral nerve 3 and 8 days following CST and
      remained unchanged following neuritis. The results of this study suggest that IL
      10's role in the neuropathic pain etiology may be specific to nerve injury type.
      Complete nerve transection increases while partial nerve injury reduces IL-10
      levels in the involved nerve, and DRG. Perineural inflammation with minimal nerve
      damage has no effect on IL-10 levels. 

PMID- 25757360
TI  - Identification of signalling cascades involved in red blood cell shrinkage and
      vesiculation.
AB  - Even though red blood cell (RBC) vesiculation is a well-documented phenomenon,
      notably in the context of RBC aging and blood transfusion, the exact signalling
      pathways and kinases involved in this process remain largely unknown. We have
      established a screening method for RBC vesicle shedding using the Ca(2+)
      ionophore ionomycin which is a rapid and efficient method to promote
      vesiculation. In order to identify novel pathways stimulating vesiculation in
      RBC, we screened two libraries: the Library of Pharmacologically Active Compounds
      (LOPAC) and the Selleckchem Kinase Inhibitor Library for their effects on RBC
      from healthy donors. We investigated compounds triggering vesiculation and
      compounds inhibiting vesiculation induced by ionomycin. We identified 12 LOPAC
      compounds, nine kinase inhibitors and one kinase activator which induced RBC
      shrinkage and vesiculation. Thus, we discovered several novel pathways involved
      in vesiculation including G protein-coupled receptor (GPCR) signalling, the
      phosphoinositide 3-kinase (PI3K)-Akt (protein kinase B) pathway, the Jak-STAT
      (Janus kinase-signal transducer and activator of transcription) pathway and the
      Raf-MEK (mitogen-activated protein kinase kinase)-ERK (extracellular signal
      regulated kinase) pathway. Moreover, we demonstrated a link between casein kinase
      2 (CK2) and RBC shrinkage via regulation of the Gardos channel activity. In
      addition, our data showed that inhibition of several kinases with unknown
      functions in mature RBC, including Alk (anaplastic lymphoma kinase) kinase and
      vascular endothelial growth factor receptor 2 (VEGFR-2), induced RBC shrinkage
      and vesiculation.

PMID- 25757363
TI  - Improved abiotic stress tolerance of bermudagrass by exogenous small molecules.
AB  - As a widely used warm-season turfgrass in landscapes and golf courses,
      bermudagrass encounters multiple abiotic stresses during the growth and
      development. Physiology analysis indicated that abiotic stresses induced the
      accumulation of ROS and decline of photosynthesis, resulting in increased cell
      damage and inhibited growth. Proteomic and metabolomic approaches showed that
      antioxidant enzymes and osmoprotectant contents (sugar, sucrose, dehydrin,
      proline) were extensively changed under abiotic stress conditions. Exogenous
      application of small molecules, such as ABA, NO, CaCl2, H2S, polyamine and
      melatonin, could effectively alleviate damages caused by multiple abiotic
      stresses, including drought, salt, heat and cold. Based on high through-put RNA
      seq analysis, genes involved in ROS, transcription factors, hormones, and
      carbohydrate metabolisms were largely enriched. The data indicated that small
      molecules induced the accumulation of osmoprotectants and antioxidants, kept cell
      membrane integrity, increased photosynthesis and kept ion homeostasis, which
      protected bermudagrass from damages caused by abiotic stresses. 

PMID- 25757365
TI  - The next breakthrough in LAM clinical trials may be their design: challenges in
      design and execution of future LAM clinical trials.
AB  - The past decade has resulted in stunning progress in the pathogenesis and therapy
      of lymphangioleiomyomatosis (LAM), culminating in the pivotal 'MILES' trial, the
      first-ever randomized, placebo-controlled trial in LAM, demonstrating the
      efficacy of sirolimus in 2011. Here, we review clinical progress since 2011,
      focusing on new therapeutic and observational trials. These trials include the
      second randomized, placebo-controlled trial, a 2-year study of doxycycline
      effectiveness in LAM. Other clinical studies have addressed lower-dose sirolimus
      and treatment of pulmonary hypertension. An improved understanding of LAM
      pathogenesis is essential to future therapeutic breakthroughs. Critical questions
      that remain to be addressed include the role of estrogen and lymphangiogenesis in
      LAM pathogenesis and therapy, mechanisms of cystic lung destruction, the role of
      autophagy and pro-survival pathways in LAM cell survival. Ultimately, achieving
      future 'breakthroughs' in LAM will require continued rigorous basic and
      preclinical investigation, innovative clinical trial design and robust
      biomarkers. 

PMID- 25757364
TI  - Functional analysis of C1 family cysteine peptidases in the larval gut of
      Tenebrio molitor and Tribolium castaneum.
AB  - BACKGROUND: Larvae of the tenebrionids Tenebrio molitor and Tribolium castaneum
      have highly compartmentalized guts, with primarily cysteine peptidases in the
      acidic anterior midgut that contribute to the early stages of protein digestion.
      RESULTS: High throughput sequencing was used to quantify and characterize
      transcripts encoding cysteine peptidases from the C1 papain family in the gut of
      tenebrionid larvae. For T. castaneum, 25 genes and one questionable pseudogene
      encoding cysteine peptidases were identified, including 11 cathepsin L or L-like,
      11 cathepsin B or B-like, and one each F, K, and O. The majority of transcript
      expression was from two cathepsin L genes on chromosome 10 (LOC659441 and
      LOC659502). For cathepsin B, the major expression was from genes on chromosome 3
      (LOC663145 and LOC663117). Some transcripts were expressed at lower levels or not
      at all in the larval gut, including cathepsins F, K, and O. For T. molitor, there
      were 29 predicted cysteine peptidase genes, including 14 cathepsin L or L-like,
      13 cathepsin B or B-like, and one each cathepsin O and F. One cathepsin L and one
      cathepsin B were also highly expressed, orthologous to those in T. castaneum.
      Peptidases lacking conservation in active site residues were identified in both
      insects, and sequence analysis of orthologs indicated that changes in these
      residues occurred prior to evolutionary divergence. Sequences from both insects
      have a high degree of variability in the substrate binding regions, consistent
      with the ability of these enzymes to degrade a variety of cereal seed storage
      proteins and inhibitors. Predicted cathepsin B peptidases from both insects
      included some with a shortened occluding loop without active site residues in the
      middle, apparently lacking exopeptidase activity and unique to tenebrionid
      insects. Docking of specific substrates with models of T. molitor cysteine
      peptidases indicated that some insect cathepsins B and L bind substrates with
      affinities similar to human cathepsin L, while others do not and have presumably
      different substrate specificity. CONCLUSIONS: These studies have refined our
      model of protein digestion in the larval gut of tenebrionid insects, and suggest
      genes that may be targeted by inhibitors or RNA interference for the control of
      cereal pests in storage areas.

PMID- 25757366
TI  - EMAS position statement: The ten point guide to the integral management of
      menopausal health.
AB  - With increased longevity and more women becoming centenarians, management of the
      menopause and postreproductive health is of growing importance as it has the
      potential to help promote health over several decades. Women have individual
      needs and the approach needs to be personalised. The position statement provides
      a short integral guide for all those involved in menopausal health. It covers
      diagnosis, screening for diseases in later life, treatment and follow-up. 

PMID- 25757367
TI  - The burden of child maltreatment in the East Asia and Pacific region.
AB  - This study estimated the health and economic burden of child maltreatment in the
      East Asia and Pacific region, addressing a significant gap in the current
      evidence base. Systematic reviews and meta-analyses were conducted to estimate
      the prevalence of child physical abuse, sexual abuse, emotional abuse, neglect,
      and witnessing parental violence. Population Attributable Fractions were
      calculated and Disability-Adjusted Life Years (DALYs) lost from physical and
      mental health outcomes and health risk behaviors attributable to child
      maltreatment were estimated using the most recent comparable Global Burden of
      Disease data. DALY losses were converted into monetary value by assuming that one
      DALY is equal to the sub-region's per capita GDP. The estimated economic value of
      DALYs lost to violence against children as a percentage of GDP ranged from 1.24%
      to 3.46% across sub-regions defined by the World Health Organization. The
      estimated economic value of DALYs (in constant 2000 US$) lost to child
      maltreatment in the EAP region totaled US $151 billion, accounting for 1.88% of
      the region's GDP. Updated to 2012 dollars, the estimated economic burden totaled
      US $194 billion. In sensitivity analysis, the aggregate costs as a percentage of
      GDP range from 1.36% to 2.52%. The economic burden of child maltreatment in the
      East Asia and Pacific region is substantial, indicating the importance of
      preventing and responding to child maltreatment in this region. More
      comprehensive research into the impact of multiple types of childhood adversity
      on a wider range of putative health outcomes is needed to guide policy and
      programs for child protection in the region, and globally. 

PMID- 25757368
TI  - Trichinella spiralis: low vaccine potential of glutathione S-transferase against
      infections in mice.
AB  - We have previously reported that Trichinella spiralis glutathione-S-transferase
      (TsGST) gene is an up-regulated gene in intestinal infective larvae (IIL)
      compared to muscle larvae (ML). In this study, the TsGST gene was cloned, and
      recombinant TsGST (rTsGST) was produced. Anti-rTsGST serum recognized the native
      TsGST by Western blotting in crude antigens of ML, adult worm (AW) and newborn
      larvae (NBL) of T. spiralis, but not in ML excretory-secretory (ES) antigens.
      Expression of TsGST was observed in all different developmental stages (IIL, AW,
      NBL and ML). An immunolocalization analysis identified TsGST in the cuticle,
      stichosome and genital primordium of the parasite. The rTsGST had GST enzymatic
      activity. After a challenge infection with T. spiralis larvae, mice immunized
      with rTsGST displayed a 35.71% reduction in adult worms and a 38.55% reduction in
      muscle larvae. The vaccination of mice with rTsGST induced the Th1/Th2-mixed type
      of immune response with Th2 predominant (high levels of IgG1) and partial
      protective immunity against T. spiralis infection. 

PMID- 25757369
TI  - First paleoparasitological record of acanthocephalan eggs from Northwestern
      Patagonia (Late Holocene, Argentina).
AB  - Eggs representative of an acanthocephalan were found in an ancient fragment of
      raptor pellet, probably belonged to the barn owl, Tyto alba, from the
      archeological site named "Epullan Chica cave." This site is a cave located at the
      southern of Neuquen Province, Patagonia, Argentina. The fragment of pellet was
      found in a layer with charcoals dated at 1980+/-80 years B.P. A total of 56 eggs
      were found. Eggs were brown colored and thick-shelled, and presented four
      membranes, the outer lightly sculpted. The embryos presented hooks in one
      extremity. Measurements ranged from 87.5 to 107.5MUm long and 50 to 57.5MUm wide.
      Eggs were very well-preserved, and were identified as belonged to Class
      Archiacanthocephala, Order Oligacanthorhynchida, Family Oligacanthorhynchidae,
      probably Macracanthorhynchus Travassos, 1917, or an unidentified species. This is
      the first report of small mammal acanthocephalans from ancient material
      worldwide. 

PMID- 25757370
TI  - Knowledge, attitude, and practices (KAP) and risk factors analysis related to
      cystic echinococcosis among residents in Tibetan communities, Xiahe County, Gansu
      Province, China.
AB  - Cystic echinococcosis (CE) is a global parasitic zoonosis caused by Echinococcus
      granulosus. The disease is highly endemic in western China, especially in Tibetan
      areas, because of poor economic development and hygiene conditions, limited
      community knowledge of CE, a large scale of dogs, and home slaughtering of
      livestock. Although many researchers have analyzed risk factors of CE
      transmission in Tibetan Plateau, there are rare reports of knowledge, attitude,
      and practice (KAP) of residents about CE in Tibetan communities. In our current
      study, community based cross-sectional study was conducted in three townships in
      Xiahe County, Gannan Tibetan Autonomous Prefectures of Gansu Province from May to
      September 2013. A total of 972 participants originating from Tibetan communities
      of 31 villages in the 3 townships were registered and data were collected using
      structured questionnaires. From the total of 972 study participants (457 males
      and 515 females), 65.9% heard of the disease CE. Most of them (96.1%) would like
      to accept CE inspection. About half of the peoples feed their dogs often and
      major of them do not play with the dogs. Risk factors included resident, knowing
      dog could be infected, knowing eating could be route of infection, oldest dog's
      age, usually feed your dog by self, feed dogs with internal organs. In general
      our findings showed that most of residents had positive attitude toward
      treatments of the disease, but their practice about disease prevention and
      control was low. Therefore, our study called for continued and strengthened
      education of changing the life style, especially the behaviors related to dogs. 

PMID- 25757371
TI  - Preparation of antibacterial silk fibroin membranes via tyrosinase-catalyzed
      coupling of epsilon-polylysine.
AB  - Silk fibroins have good biocompatibility and could be used to form a variety of
      regenerated functional biomaterials. In this study, enzymatic oxidization of silk
      fibroins with tyrosinase (TYR) was carried out, followed by coupling of epsilon
      polylysine (epsilon-PLL) for improving antibacterial ability of the fibroin-based
      biomaterial. Trinitrobenzene sulfonic acid (TNBS) was selectively used to
      incubate with silk fibroins prior to TYR treatment, aiming at preventing the self
      crosslinking of silk fibroins during enzymatic oxidation. The results indicated
      that tyrosine residues in silk fibroins could be converted to reactive
      dioxyphenylalanine and o-quinone residues TYR successively. TNBS pretreatment
      inhibited the self-crosslinks of silk fibroins and promoted the successive
      coupling of epsilon-PLL to fibroin proteins with high graft yield. The combined
      use of TNBS, TYR, and epsilon-PLL treatments endowed fibroin membrane with
      satisfactory antibacterial ability against Staphylococcus aureus, and the
      obtained durability was also acceptable. The changes in surface potential and
      amine acid composition for the fibroin membranes verified the favorable actions
      of the combined treatment. The present method could be potentially utilized for
      enzymatic functionalization of various fibroin-based biomaterials. 

PMID- 25757372
TI  - Parents' beliefs about the healthfulness of sugary drink options: opportunities
      to address misperceptions.
AB  - OBJECTIVE: To assess potential misperceptions among parents regarding the
      healthfulness of sugary drinks for their children. DESIGN: Online survey of
      parents. Participants identified the categories and specific brands of sugary
      drinks they provided for their children. They also indicated their perceptions of
      sugary drink categories and brands as healthy options for children, perceived
      importance of on-package claims in purchase decisions and their concerns about
      common sugary drink ingredients. SETTING: Online market research panel. SUBJECTS:
      Parents (n 982) of 2- to 17-year-olds, 46 % non-white or Hispanic. RESULTS:
      Ninety-six per cent of parents provided on average 2.9 different categories of
      sugary drinks for their children in the past month. Flavoured waters, fruit
      drinks and sports drinks were rated as the healthiest sugary drink categories.
      Across all categories and brands, parents who purchased specific products rated
      them as significantly healthier than those who did not (P<0.05). Over half of
      parents reported concern about caffeine, sugar and artificial sweeteners in
      sugary drinks that their children consume and approximately one-third reported
      that on-package ingredient claims were important in their purchase decisions.
      CONCLUSIONS: Nearly all parents provide sugary drinks for their children and many
      believe that some sugary drinks are healthy options for children, particularly
      flavoured waters, fruit drinks and sports drinks. Furthermore, many parents rely
      upon on-package claims in their purchase decisions. Given excessive consumption
      of added sugar by children in the home, there is a continuing need to address
      parents' misperceptions about the healthfulness of many sugary drink products.

PMID- 25757373
TI  - Common variant within the FTO gene, rs9939609, obesity and type 2 diabetes in
      population of Karachi, Pakistan.
AB  - AIM: To determine the effect of genetic variants within the FTO gene (rs9939609)
      on obesity related traits and type 2 diabetes in South Asian population of
      Karachi, Pakistan. METHODS: A case-control study was conducted at Baqai Institute
      of Diabetology and Endocrinology (BIDE), Baqai Medical University situated in
      Karachi. A total of 296 patients with known type 2 diabetes and 198 controls aged
      greater than and equal to 45 years were recruited. The Anthropometric, clinical
      and biochemical data was collected on a structured questionnaire. Single
      nucleotide polymorphism (SNP) in FTO gene was identified by Amplification
      Refractory Mutation System-Polymerase Chain Reaction (ARMS-PCR). Association
      between the single nucleotide polymorphism and categorical variables such as type
      2 diabetes and obesity category was tested through logistic regression analysis.
      RESULTS: We observed a strong association of the minor allele A at rs9939609 with
      type 2 diabetes. Significant difference was observed in frequency of FTO genotype
      when diabetic subjects were compared with controls in co dominant, dominant and
      recessive models. This association remained significant even after adjusting for
      body mass index (BMI) and for waist circumference. The frequency of homozygous
      risk Alleles (AA) was found to be higher in obese & overweight (>= 23 kg/m(2))
      and females with central obesity in our study population. The association of FTO
      variant with BMI and central obesity does not reach to statistical significance.
      CONCLUSION: In the study population of South Asian ancestry, variants of the FTO
      gene predispose to type 2 diabetes, but not entirely through their effect on BMI.

PMID- 25757374
TI  - Microstructural abnormalities in children with post-traumatic stress disorder: a
      diffusion tensor imaging study at 3.0T.
AB  - Posttraumatic stress disorder (PTSD) is a severe anxiety disorder characterized
      by re-experiencing, avoidance and hyperarousal. Brain microstructure
      abnormalities in PTSD, especially in children, are not yet well characterized.
      The aim of this study was to use MR diffusion tensor imaging (DTI) to identify
      brain microstructure alterations in children with PTSD compared to non-PTSD
      controls who experienced the same time-limited trauma. We studied 27 children
      with PTSD and 24 age- and gender-matched traumatized controls without PTSD, who
      all experienced the 2008 Sichuan major earthquake. DTI data were acquired and
      analyzed in terms of fractional anisotropy (FA), mean diffusivity (MD), radial
      diffusivity (RD) and axial diffusivity (AD). Children with PTSD showed an
      abnormal pattern, not only of FA, but also of the diffusivity measures MD, AD and
      RD. Most of the abnormal brain regions belonged to two important networks: the
      default-mode network, including precuneus and angular gyrus, and the salience
      network, including insula, putamen and thalamus. This DTI study identifies
      microstructural abnormalities of children with PTSD after a major earthquake, our
      results are consistent with the suggestion that pediatric PTSD is accompanied by
      a connectivity disequilibrium between the salience and default-mode networks, a
      finding of potential pathophysiological significance. 

PMID- 25757375
TI  - Orbitofrontal sulcogyral pattern and olfactory sulcus depth in the schizophrenia
      spectrum.
AB  - Morphological changes in the orbitofrontal cortex (OFC), such as an altered
      sulcogyral pattern of the 'H-shaped' orbital sulcus and a shallow olfactory
      sulcus, have been demonstrated in schizophrenia, possibly reflecting deviations
      in early neurodevelopment. However, it remains unclear whether patients with
      schizotypal features exhibit similar OFC changes. This magnetic resonance imaging
      study examined the OFC sulcogyral pattern (Types I, II, III, and IV) and
      olfactory sulcus morphology in 102 patients with schizophrenia, 47 patients with
      schizotypal disorder, and 84 healthy controls. The OFC sulcogyral pattern
      distribution between the groups was significantly different on the right
      hemisphere, with the schizophrenia patients showing a decrease in Type I (vs
      controls and schizotypal patients) and an increase in Type III (vs controls)
      expression. However, the schizotypal patients and controls did not differ in the
      OFC pattern. There were significant group differences in the olfactory sulcus
      depth bilaterally (schizophrenia patients < schizotypal patients < controls). Our
      findings suggest that schizotypal disorder, a milder form of schizophrenia
      spectrum disorders, partly shares the OFC changes (i.e., altered depth of the
      olfactory sulcus) with schizophrenia, possibly reflecting a common disease
      vulnerability. However, altered distribution of the OFC pattern specific to
      schizophrenia may at least partly reflect neurodevelopmental pathology related to
      a greater susceptibility to overt psychosis. 

PMID- 25757377
TI  - Persistent sensitisation to the locomotor activating effects of MDMA following
      MDMA self-administration in rats.
AB  - Effects of MDMA exposure on MDMA-produced hyperactivity are dependent on the
      exposure regimen; high-dose exposure produced tolerance whereas repeated,
      intermittent exposure produced sensitised responses. In the present study we
      measured the impact of MDMA self-administration on MDMA-produced hyperactivity.
      Rats self-administered a total of 165mg/kg MDMA during daily 2h sessions. Control
      rats self-administered vehicle solution and were matched to the MDMA self
      administering rats so that they had the same number of daily exposures to
      handling and the chamber. Behavioural measures were collected either 5 or 14days
      following the last MDMA self-administration session and 14days following the last
      vehicle self-administration session. Following a 30min habituation period, rats
      received an injection of MDMA (10.0mg/kg, IP) and various measures of MDMA
      produced hyperactivity were measured. Speed of forward locomotion and rearing,
      behaviours that are often attributed to dopaminergic mechanisms, increased
      following both abstinence periods. These data are consistent with a persistent
      sensitisation of dopamine substrates as a result of MDMA self-administration.

PMID- 25757378
TI  - Excitation and quenching mechanisms in the near-UV photodissociation of CH3Br and
      CH3Cl adsorbed on D2O or CH3OH on Cu(110).
AB  - Photochemical processes for CH3X (X = Cl, Br, I) adsorbed on top of thin films of
      D2O or CH3OH on a Cu(110) substrate is studied by time-of-flight mass
      spectrometry for a range of UV wavelengths (351-193 nm). Photodissociation via
      dissociative electron attachment by photoelectrons and by neutral
      photodissociation is identified and quantified based on the observed dynamics of
      the desorbing CH3 fragments. Photoelectron-driven dissociation of CH3X is found
      to be a maximum for monolayer quantities of the D2O or CH3OH on Cu(110), but with
      differing kinetic energy release on the two substrates. The dynamics of CH3Br and
      CH3Cl photodissociation qualitatively differ on CH3OH/Cu(110) as compared to
      D2O/Cu(110), which is ascribed to differing molecular structures for these
      systems. Evidence is presented for an efficient inter-molecular quenching
      mechanism for neutral photoexcitation of CH3Cl and CH3Br on the CH3OH/Cu(110)
      substrate. 

PMID- 25757376
TI  - RhoGTPase signalling at epithelial tight junctions: Bridging the GAP between
      polarity and cancer.
AB  - The establishment and maintenance of epithelial polarity must be correctly
      controlled for normal development and homeostasis. Tight junctions (TJ) in
      vertebrates define apical and basolateral membrane domains in polarized epithelia
      via bi-directional, complex signalling pathways between TJ themselves and the
      cytoskeleton they are associated with. RhoGTPases are central to these processes
      and evidence suggests that their regulation is coordinated by interactions
      between GEFs and GAPs with junctional, cytoplasmic adapter proteins. In this
      InFocus review we determine that the expression, localization or stability of a
      variety of these adaptor proteins is altered in various cancers, potentially
      representing an important mechanistic link between loss of polarity and cancer.
      We focus here, on two well characterized RhoGTPases Cdc42 and RhoA who's GEFs and
      GAPs are predominantly localized to TJ via cytoplasmic adaptor proteins. 

PMID- 25757379
TI  - A topical haemoglobin spray for oxygenating pressure ulcers: a pilot study.
AB  - The effect of pressure ulcers on patient quality of life have been recognised as
      a real problem for many years, and the need for robust and effective management
      of pressure ulcers is now a prominent national health-care issue. Myriad
      different interventions exist for the treatment of pressure ulcers, including
      clinically effective dressings and pressure-relieving devices, yet many pressure
      ulcers still do not heal and often become a chronic wound. This is the second of
      a series of articles (Norris, 2014) discussing the clinical evaluation of a
      topical oxygen therapy in practice. It describes a small evaluation involving 18
      patients with pressure ulcers. The study set out to determine the effect of a
      topical oxygen therapy on wound size. The therapy comprises a canister that
      sprays pure haemoglobin in a water solution into or onto the wound. The
      haemoglobin spray needs to be used at least once every 3 days, does not require
      training on its use and can be used in any care setting. Overall, results
      identified wound healing progression in all 18 wounds and wound size reduction in
      17 of the 18 wounds.

PMID- 25757380
TI  - The thickness of exudate: does it matter?
AB  - The majority of chronic wounds are managed in the community by the district
      nursing team. With increasing constraints on the health-care budget, it can be
      tempting to manage exudate by focusing solely on the exudate-handling capability
      of some of the more absorbent dressings available. However, exudate levels and
      viscosity can change depending on the patient and the wound, with exudate being a
      marker of potential infection. Ongoing assessment of the wound, the exudate and
      the patient is pivotal to effective wound management, with timely and appropriate
      intervention being key. This article discusses this management, with particular
      focus on dealing with thick exudate. 

PMID- 25757381
TI  - Prevention and management of diabetic foot ulcers.
AB  - As part of an annual foot review, trained and competent personnel should examine
      patients' feet to detect risk factors for ulceration. Foot examination with shoes
      and stockings removed should include: palpation of foot pulses; testing foot
      sensations using 10g monofilament or vibration; inspection for significant callus
      or deformed nails; inspection for any structural deformity; asking about any
      previous ulceration; checking for signs of ulceration; asking about any pain; and
      inspecting footwear. Following assessment, a foot risk classification score
      should be given. The person with diabetes should then be informed of their risk
      score, with education offered regarding future foot-care management. Diabetic
      foot complications include ulceration, Charcot foot, painful neuropathy, gangrene
      and amputation. Risk factors for ulceration include non-palpable pulses,
      insensate foot, significant callus, deformed nails, history of previous ulcer or
      amputation, tissue damage or signs of ulceration, foot pain and unsuitable
      footwear. 

PMID- 25757382
TI  - An evaluation of short-stretch compression systems for chronic lower-limb leg
      ulcers.
AB  - An evaluation of a new short-stretch compression system (CoFlex UBZ, TLC and TLC
      Lite, Aspen Medical Europe Ltd) was undertaken in four leg ulcer clinics. A total
      of 19 patients aged 42-93 years were treated for up to 4 weeks, or until healed.
      Collated data included age, underlying diseases, leg ulcer type, ulcer duration
      and current treatment. The evaluation included quality of life measurements, wear
      time, slippage, exudate strikethrough and pain using a numerical pain score.
      Patients were asked to document sleep patterns. Compression was applied according
      to clinical need. Inclusion criteria were non-healing wounds on the lower limb
      existing for more than 6 weeks that were suitable for compression. Exclusion
      criteria included patients with untreated peripheral disease, ankle-brachial
      pressure index (ABPI)<0.5 or those unable to consent. Staff were asked to rate
      performance, wear time, fluid handling and conformability. Wound tissue types
      improved significantly for n=16 (84%) patients. Pain scores reduced significantly
      by week 2, n=11 (58%) patient leg ulcers had improved, n=2 (11%) patients in
      standard compression noted a marked reduction in malodour and sloughy tissue.
      n=16 (84%) rated the overall performance as 'very good' or 'good'. A detailed
      cost analysis was undertaken on one patient, suggesting a potential cost saving
      of L186.92 per month and a cost efficiency saving of 43.4%. 

PMID- 25757383
TI  - Treating a leg ulcer patient with complex comorbidities: a case study.

PMID- 25757384
TI  - Lindsay leg club foundation.

PMID- 25757385
TI  - Apples and oranges.

PMID- 25757386
TI  - Woundcare4Heroes.

PMID- 25757387
TI  - Biofilm in wound care.
AB  - A biofilm can be described as a microbial colony encased in a polysaccharide
      matrix which can become attached to a wound surface. This can affect the healing
      potential of chronic wounds due to the production of destructive enzymes and
      toxins which can promote a chronic inflammatory state within the wound. Biofilms
      can be polymicrobial and can result in delayed wound healing and chronic wound
      infection resistant to antibiotics, leading to prolonged hospitalisation for some
      patients. There appears to be a correlation between biofilms and non-healing in
      chronic wounds. It is suggested that biofilms are a major player in the
      chronicity of wounds. They are a complex concept to diagnose and management needs
      to be multifactorial. 

PMID- 25757388
TI  - Constitutive and stress-inducible overexpression of a native aquaporin gene
      (MusaPIP2;6) in transgenic banana plants signals its pivotal role in salt
      tolerance.
AB  - High soil salinity constitutes a major abiotic stress and an important limiting
      factor in cultivation of crop plants worldwide. Here, we report the
      identification and characterization of a aquaporin gene, MusaPIP2;6 which is
      involved in salt stress signaling in banana. MusaPIP2;6 was firstly identified
      based on comparative analysis of stressed and non-stressed banana tissue derived
      EST data sets and later overexpression in transgenic banana plants was performed
      to study its tangible functions in banana plants. The overexpression of
      MusaPIP2;6 in transgenic banana plants using constitutive or inducible promoter
      led to higher salt tolerance as compared to equivalent untransformed control
      plants. Cellular localization assay performed using transiently transformed onion
      peel cells indicated that MusaPIP2;6 protein tagged with green fluorescent
      protein was translocated to the plasma membrane. MusaPIP2;6-overexpressing banana
      plants displayed better photosynthetic efficiency and lower membrane damage under
      salt stress conditions. Our results suggest that MusaPIP2;6 is involved in salt
      stress signaling and tolerance in banana. 

PMID- 25757389
TI  - [Participative action research; self-care education for the mature adult, a
      dialogic and empowered process].
AB  - OBJECTIVE: Explore and transform dialogic-reflexive learning processes oriented
      to self-care, capacitation, empowerment and health promotion for "mature-adult"
      collective. DESIGN: Participative action research on a qualitative and
      sociocritic approach. Data generation methods are SITE: Field work focuses on the
      development of the educational program "Care is in your hands" that takes place
      in two villages (Primary Care. Comarca Araba). PARTICIPANTS: Through a
      theoretical sampling involved people who are in a "mature-adult" life stage and
      three nurses with extensive experience in development health education programs.
      METHODS: Participant observation where health education sessions are recorded in
      video and group reflection on action. To triangulate the data, have been made in
      depth interviews with 4 participants. Carried out a content and discourse
      analysis. RESULTS: Participant and nurses' Previous Frameworks, and these last
      ones' discourses as well, reveal a current technical rationality (unidirectional,
      informative,.) yet in practice that perpetuates the role of passive recipient of
      care. Educational keys constructed from a viewpoint of Dialogic Learning emerge
      as elements that facilitate overcoming these previous frames limitations.
      Finally, Reflective Learning launched, has provided advance in professional
      knowledge and improve health education. CONCLUSIONS: Dialogical learning emerges
      as key to the training and empowerment, where we have seen how practical
      reflexive, and not technical, rationality is meanly useful confronting ambiguous
      and complex situations of self-care practice and education.

PMID- 25757390
TI  - Barriers to using molecularly typed minority red blood cell donors in support of
      chronically transfused adult patients with sickle cell disease.
AB  - BACKGROUND: Much effort and resources have been devoted to programs that provide
      transfusion support for patients with sickle cell disease (SCD). The focus of
      many donor programs is to prevent alloimmunization by recruiting racially matched
      African American donors to limit the red blood cell (RBC) antigenic differences
      that exist between Caucasian donors and patients with SCD. STUDY DESIGN AND
      METHODS: In this study, we evaluated the RBC antigen characteristics of both the
      recipient population with SCD and the African American donor population from 2010
      to 2013. We evaluated the genotype-derived predicted antigen frequencies of the
      donors and compared these frequencies with those of the population supported by
      these units. Specific attention was given to the alloimmunization rate over the 3
      years and the number of D- units provided to D+ patients. RESULTS: We recruited
      6066 African American donors during the 3-year study period with 77.3% of these
      donors donating no more than twice. The observed genotype-derived predicted
      antigen frequencies were similar to the expected frequencies, and the antigen
      frequencies of a cohort of 54 adult patients with SCD (p > 0.05). Twelve patients
      (22.2%) with SCD had alloantibodies and five of these patients developed these
      antibodies while receiving Rh and K antigen-matched blood during the study
      interval. Finally, we found that 607 (37.1%) D- units were diverted to D+
      patients. CONCLUSIONS: New recruitment and prevention strategies are needed to
      increase the pool of available antigen-matched RBCs and decrease alloimmunization
      risk for this patient population.

PMID- 25757391
TI  - A proposed definition of rare diseases for China: from the perspective of return
      on investment in new orphan drugs.
AB  - A prevalence threshold to define rare diseases is needed for orphan drug
      designation. Here, we propose a bottom-up approach to defining rare diseases for
      China, based on the minimum number of patients needed for the industry to make a
      reasonable profit on a new drug. To obtain this patient population size, we
      considered three factors: (1) the industry research and development cost per new
      drug; (2) the sales per new drug to recoup its research and development costs and
      generate profit; (3) the highest affordable cost for one patient's treatment in a
      given healthcare system. Using this model, we estimate that, with the current
      level of innovation in the pharmaceutical industry in China, between 300,000 and
      500,000 patients could be a reference threshold to define rare diseases. Compared
      with other proposals, this evidence-based definition is more useful for designing
      rare diseases and orphan drug policies for China. 

PMID- 25757392
TI  - Surgical management of laryngeal invasion by papillary thyroid carcinoma: a
      retrospective analysis.
AB  - BACKGROUND: Papillary thyroid carcinoma (PTC) has an excellent prognosis.
      Although rare, PTC invasion into the upper aerodigestive tract can adversely
      affect patient prognosis and quality of life. This study investigated the impact
      of tumor excision on the prognosis and postoperative status of patients with PTC
      invasion of the larynx. METHODS: Data on PTC patients who underwent surgery at
      the author's institution between April 1981 and March 2010 were retrospectively
      reviewed, and 55 patients with thyroid cartilage invasion were enrolled. Curative
      resection was performed for all patients, and laryngeal function was preserved or
      reconstructed when possible. RESULTS: Of the 55 patients, 40 and 15 patients had
      superficial and intraluminal invasion of the larynx, respectively. The 10-year
      disease-specific survival rates were 81.0% and 61.4% in patients who underwent
      surgery for superficial and intraluminal invasion of the larynx, respectively.
      Only two patients (3.6%) had an isolated locoregional recurrence in the larynx.
      Four patients (7.3%) underwent total laryngectomy during the initial surgery or
      surgery for laryngeal recurrence. Permanent stoma remained in 26 patients (47%):
      14 with laryngeal invasion, and 12 with invasion of other aerodigestive
      structures. The number of invaded aerodigestive structures including the larynx
      was correlated with the presence of permanent stoma. CONCLUSIONS: In many
      patients, PTC invasion of the larynx remained at the thyroid cartilage or
      paraglottic space. Most patients did not require total laryngectomy. Good
      locoregional control was achieved with surgical tumor excision in patients with
      laryngeal invasion. Distant metastases were the major cause of death in patients
      with PTC invasion of the larynx.

PMID- 25757393
TI  - Stimulated emission within the exciplex band by plasmonic-nanostructured
      polymeric heterojunctions.
AB  - Organic heterojunctions have been extensively employed in the design of light
      emitting diodes, photovoltaic devices, and thin-film field-effect transistors,
      which can be achieved by constructing a bilayer or a multi-layered thin-film
      deposition, or by blending two or more organic semiconductors with different
      charge-transport performances. Charge transfer excited states or exciplex may
      form on the heterointerfaces. Efficient light-emitting diodes have been
      demonstrated using exciplex emission. However, lasing or stimulated emission
      processes have not been observed with exciplex formation at organic
      heterojunctions. In this work, we demonstrate strong coherent interaction between
      photons and exciplex formation in the blends of poly-9,9'-dioctylfluorene-co-bis
      N,N'-(4-butylphenyl)-bis-N,N'-phenyl-l,4-phenylenediamine (PFB) and poly-9,9'
      dioctylfluorene-co-benzothiadiazole (F8BT), leading to transient stimulated
      exciplex emission. The responsible mechanisms involve plasmonic local-field
      enhancement and plasmonic feedback in a three-dimensional gold-nanoparticle
      matrix. 

PMID- 25757394
TI  - Effects of chronic administration of valproic acid to epileptic patients on
      coagulation tests and primary hemostasis.
AB  - Valproic acid (VPA) is an antiepileptic drug that has been associated with
      impaired hemostasis and increased risk for postsurgical bleeding. However, the
      published reports provide controversial results. We measured parameters of
      primary hemostasis in VPA-treated patients with epilepsy, focusing on adenosine
      nucleotide-dependent platelet responses, which play a central role in primary
      hemostasis. We enrolled 20 cases (epileptic patients receiving treatment with
      VPA) and 20 controls (12 epileptic patients receiving treatment with drugs
      different from VPA and 8 healthy subjects). Measurements included prothrombin
      time (PT), activated partial thromboplastin time (APTT), platelet count, platelet
      function analyzer (PFA)-100 closure times, plasma von Willebrand factor levels,
      platelet content of ADP, ATP, and serotonin (all stored in platelet dense
      granules), and platelet shape change and aggregation induced by ADP and other
      platelet agonists, including the ATP analog alpha,beta-methylene-ATP. The plasma
      concentration of VPA was in the therapeutic range in 17 patients and slightly
      above the upper limit in 3 patients. There were no statistically significant
      differences in any of the studied parameters in cases versus controls. Our
      thorough controlled study failed to show that chronic treatment with VPA induces
      significant abnormalities of coagulation and primary hemostasis. Therefore, VPA,
      when present in the circulation in the therapeutic range, does not impair
      hemostasis. 

PMID- 25757395
TI  - Monitoring urinary mercapturic acids as biomarkers of human dietary exposure to
      acrylamide in combination with acrylamide uptake assessment based on duplicate
      diets.
AB  - The present human intervention study investigated the relation between the intake
      of acrylamide (AA) in diets with minimized, low, and high AA contents and the
      levels of urinary exposure biomarkers. As biomarkers, the mercapturic acids, N
      acetyl-S-(carbamoylethyl)-L-cysteine (AAMA), and N-acetyl-S-(1-carbamoyl-2
      hydroxyethyl)-L-cysteine (GAMA) were monitored. The study was performed with 14
      healthy male volunteers over a period of 9 days, under controlled conditions
      excluding any inadvertent AA exposure. Dietary exposure to AA was measured by
      determining AA contents in duplicates of all meals consumed by the volunteers.
      The study design included an initial washout period of 3 days on AA-minimized
      diet, resulting in dietary AA exposure not exceeding 41 ng/kg bw/d. Identical
      washout periods of 2 days each followed the AA exposure days (day 4, low
      exposure, and day 7, high exposure). At the respective AA intake days, volunteers
      ingested 0.6-0.8 (low exposure) or 1.3-1.8 (high exposure) MUg AA/kg bw/d with
      their food. Both low and high AA intakes resulted in an AAMA output within 72 h
      corresponding to 58 % of the respective AA intake. At the end of the initial 3
      day washout period, an AAMA baseline level of 93 +/- 31 nmol/d was recorded,
      suggestive for an assumed net AA baseline exposure level of 0.2-0.3 MUg AA/kg
      bw/d.

PMID- 25757397
TI  - Association Between IL-27 Genetic Polymorphisms and Rheumatoid Arthritis: Comment
      on the Article by A. Paradowska-Gorycka et al.

PMID- 25757396
TI  - Influence of micronization on improving phytoestrogenic effects of wheat bran.
AB  - The influence of micronization on improving the phytoestrogenic effects of wheat
      bran was studied. Wheat bran samples were prepared by ball milling, and an animal
      experiment was carried out by feeding 8-month-old female rats wheat bran. The
      effect of wheat bran samples on serum estradiol (E2) and progesterone (P) levels
      of female 8-month-old rats was investigated. The wheat bran with a median
      diameter of 392.1 MUm was micronized to 91.1 and 9.7 MUm in median diameter by
      dry milling and wet milling for 5 hours, respectively. Microscopic observation
      and X-ray diffraction revealed more potential damage from wet milling than dry
      milling on the crystal structure of wheat bran granules. Almost all particles
      were dissolved and there was no obvious crystal peak in the 5-hour wet-milled
      wheat bran. The serum E2 and P levels of the 8-month-old rats fed wet-milled bran
      were increased significantly, 2.2 times higher than that of the same aged control
      group. The experimental results indicated that wet milling could destroy the
      crystal structure of wheat bran granules and improve the phytoestrogenic effects
      of wheat bran. 

PMID- 25757398
TI  - Impaired gait function in adults with cerebral palsy is associated with reduced
      rapid force generation and increased passive stiffness.
AB  - OBJECTIVE: It is still not clarified whether spasticity contributes to
      impairments of gait function. Here we compared biomechanical measures of muscle
      weakness and stiffness of ankle muscles to impairments of gait function in adults
      with cerebral palsy (CP). METHODS: Twenty-four adults with CP (mean age 34.3,
      range 18-57 years) and fifteen healthy age-matched controls were biomechanically
      measured for passive and reflex-mediated stiffness of the ankle plantarflexors at
      rest, maximal voluntary plantarflexion and dorsiflexion effort (MVCpf,df) and
      rate of force development (RFDpf,df). Kinematic analysis of the ankle joint
      during treadmill walking was obtained by 3-D motion analysis. RESULTS: Passive
      stiffness was significantly increased in adults with CP compared to controls.
      Passive stiffness and RFDdf were correlated to reduced toe lift. RFDpf provided
      the best correlation to push-off velocity, range of movement in the ankle joint
      and gait speed. Reflex-mediated stiffness was not correlated to any parameters of
      impaired gait. CONCLUSIONS: Impaired gait function in adults with CP is
      associated with reduced RFD and increased passive stiffness of ankle muscles.
      SIGNIFICANCE: These findings suggest that reduced rapid force generation and
      increased passive stiffness of ankle muscles rather than increased reflex
      mediated stiffness (spasticity) likely contributes to impaired gait function in
      adults with CP.

PMID- 25757399
TI  - Mitochondrial dysfunction and mitophagy in Parkinson's: from familial to sporadic
      disease.
AB  - Parkinson's disease (PD) is a progressive neurodegenerative disorder
      characterised by the preferential loss of dopaminergic neurons in the substantia
      nigra. Mitochondrial dysfunction is increasingly appreciated as a key determinant
      of dopaminergic neuronal susceptibility in PD and is a feature of both familial
      and sporadic disease, as well as in toxin-induced Parkinsonism. Recently, the
      mechanisms by which PD-associated mitochondrial proteins phosphatase and tensin
      homolog deleted on chromosome 10 (PTEN)-induced putative kinase 1 (PINK1) and
      parkin function and induce neurodegeneration have been identified. In addition,
      increasing evidence implicates other PD-associated proteins such as alpha
      synuclein (alpha-syn) and leucine-rich repeat kinase 2 (LRRK2) in mitochondrial
      dysfunction in genetic cases of PD with the potential for a large functional
      overlap with sporadic disease. This review highlights how recent advances in
      understanding familial PD-associated proteins have identified novel mechanisms
      and therapeutic strategies for addressing mitochondrial dysfunction in PD. 

PMID- 25757400
TI  - The twisted relation between Pnu and SWEET transporters.
AB  - The evolutionary relation between sugar and vitamin transporters from the SWEET
      and Pnu families is unclear. They have similar 3D structures, but differ in the
      topology of their secondary structure elements, and lack significant sequence
      similarity. Here we analyze the structures and sequences of different members of
      the SWEET and Pnu transporter families and propose an evolutionary pathway by
      which they may have diverged from a common ancestor. A 3D domain swapping event
      can explain the topological differences between the families, as well as the
      puzzling observation that a highly conserved and essential sequence motif of the
      SWEET family (the PQ loop) is absent from the Pnu transporters. 

PMID- 25757401
TI  - Decoding and reprogramming complex polyketide assembly lines: prospects for
      synthetic biology.
AB  - Bacterial modular type I polyketide synthases (PKSs) represent giant
      megasynthases that produce a vast number of complex polyketides, many of which
      are pharmaceutically relevant. This review highlights recent advances in
      elucidating the mechanism of bacterial type I PKSs and associated enzymes, and
      outlines the ramifications of this knowledge for synthetic biology approaches to
      expand structural diversity. New insights into biosynthetic codes and structures
      of thiotemplate systems pave the way to rational bioengineering strategies.
      Through advances in genome mining, DNA recombination technologies, and
      biochemical analyses, the toolbox of non-canonical polyketide-modifying enzymes
      has been greatly enlarged. In addition to various chain-branching and chain
      fusing enzymes, an increasing set of scaffold modifying biocatalysts is now
      available for synthetically hard-to-emulate reactions. 

PMID- 25757402
TI  - Multi-scale modeling for the transmission of influenza and the evaluation of
      interventions toward it.
AB  - Mathematical modeling of influenza epidemic is important for analyzing the main
      cause of the epidemic and finding effective interventions towards it. The
      epidemic is a dynamic process. In this process, daily infections are caused by
      people's contacts, and the frequency of contacts can be mainly influenced by
      their cognition to the disease. The cognition is in turn influenced by daily
      illness attack rate, climate, and other environment factors. Few existing methods
      considered the dynamic process in their models. Therefore, their prediction
      results can hardly be explained by the mechanisms of epidemic spreading. In this
      paper, we developed a heterogeneous graph modeling approach (HGM) to describe the
      dynamic process of influenza virus transmission by taking advantage of our unique
      clinical data. We built social network of studied region and embedded an Agent
      Based Model (ABM) in the HGM to describe the dynamic change of an epidemic. Our
      simulations have a good agreement with clinical data. Parameter sensitivity
      analysis showed that temperature influences the dynamic of epidemic significantly
      and system behavior analysis showed social network degree is a critical factor
      determining the size of an epidemic. Finally, multiple scenarios for vaccination
      and school closure strategies were simulated and their performance was analyzed. 

PMID- 25757403
TI  - Training the removal of negative information from working memory: A preliminary
      investigation of a working memory bias modification task.
AB  - Rumination in depressed adults is associated with a bias toward retaining
      negative information in working memory. We developed a task designed to modify
      this cognitive bias by having subjects repeatedly practice removing negative
      words from working memory, thereby enabling them to retain positive and neutral
      words. To assess the efficacy of this task, we recruited 60 adults who reported
      elevated repetitive negative thought (RNT) and randomly assigned them to receive
      a single administration of either the working memory bias modification (WMBM)
      task or a control task. Subjects in the WMBM condition exhibited greater
      reduction in proactive interference for negative information than did those in
      the control condition. These results suggest that the WMBM task reduces biased
      retention of negative information in working memory and, thus, may be useful in
      investigating the possible causal role of this cognitive bias in RNT or
      depression. 

PMID- 25757404
TI  - Prospective evaluation of regional oxygen saturation to estimate central venous
      saturation in sepsis.
AB  - Current treatment guidelines for sepsis claim an early goal-directed hemodynamic
      optimization including fluid resuscitation, use of vasopressors and inotropic
      agents. We investigated the correlation between the prominent treatment goal
      central venous saturation (ScvO2) and the frontal and the thenar regional oxygen
      saturation (rSO2) measured by near infrared spectroscopy. Secondary, we examined
      the value of ScvO2, lactate levels and rSO2 as surrogate markers of an impaired
      tissue oxygenation for outcome prediction in sepsis. This prospective,
      observational study was performed at the surgical intensive care unit of the
      University Hospital Giessen. A total of 50 patients with sepsis, severe sepsis or
      septic shock were included. ScvO2, rSO2 and lactate were measured at sepsis
      diagnosis (baseline), 24 and 48 h, thereafter. We investigated the predictive
      value of frontal and thenar rSO2 for a decreased SvcO2 under 70%. For survivor
      and non-survivors ScvO2, rSO2 and lactate were analysed. Patients with ScvO2 >70%
      showed a trend to higher levels of fontal rSO2 (62.81 +/- 8.06 vs. 53.54 +/-
      15.48; p = 0.058). ROC-analysis revealed a minor prediction of a decreased ScvO2
      by frontal rSO2 levels at baseline (AUC = 0.687; 95% CI 0.511-0.863; p = 0.047).
      Combined measurements of lactate and ScvO2 showed significantly elevated
      mortality for patients with ScvO2 >=70% and lactate levels >=2.5 mmol/l (log rank
      test p = 0.004). In the group with ScvO2 <70% and lactate levels <2.5 mmol/l no
      patients died during the observation period. Frontal rSO2 correlates with ScvO2
      but both frontal and thenar rSO2 do not exactly discriminate between patients
      with high or low ScvO2 in sepsis. The combination of elevated lactate >2.5 mmol/l
      and ScvO2 >70 % is highly associated with poor outcome in ICU patients with
      sepsis, severe sepsis and septic shock.

PMID- 25757405
TI  - Performance of an active inspired hypoxic guard.
AB  - Current hypoxic guards systems fail to maintain the inspired O2 concentration
      (FIO2) >= 21 % across the entire fresh gas flow (FGF) range when a second carrier
      gas is used (N2O or air). We examined the performance of the Maquet O2
      Guard((r)), a smart hypoxic guard that increases O2 delivery if an inspired
      hypoxic mixture is formed. After obtaining IRB approval and informed consent, 12
      ASA I-II patients were enrolled. During anesthesia with sevoflurane in O2/air,
      the O2 Guard((r)) was tested by administering O2/air at the following delivered
      hypoxic guard limits [expressed as (total FGF in L min(-1); FDO2 in %)] for 4 min
      each: [0.3;67], [0.4;50], [0.6;34], [0.8;25], [1.0;21], [1.2;21], [1.5;21],
      [2;21], [3;21], and [5;21]. The following data were collected: (1) time from FIO2
      = 30 to 20 %; (2) time from FIO2 = 20 % to O2 Guard((r)) activation; (3) time
      from O2 Guard((r)) activation to FIO2 = 25 %; (4) FGF and FDO2 used by the O2
      Guard. If SpO2 was <90 % for 10 s or longer at any time, the patient was
      excluded. Three patients were excluded for low SpO2. The incidence of FIO2 < 21 %
      was 100 % within the 1-2 L min(-1) FGF range. The O2 Guard((r)) was activated
      within 20 s after FIO2 became 20 %, except in one patient where FIO2 oscillated
      between 20 and 21 %. FDO2 was increased to 60 % and FGF to 1 L min(-1) (the
      latter only if it was lower than 1 L min(-1) prior to activation of the O2
      Guard). FIO2 increased to 25 % within 55 s after O2 Guard activation in all
      patients. The O2 Guard((r)), an active inspired hypoxic guard, rapidly reverses
      and limits the duration of inspired hypoxic episodes when the delivered hypoxic
      guard fails to do so. 

PMID- 25757406
TI  - Transition in sexual system and sex chromosome evolution in the tadpole shrimp
      Triops cancriformis.
AB  - Transitions in sexual system and reproductive mode may affect the course of sex
      chromosome evolution, for instance by altering the strength of sexually
      antagonistic selection. However, there have been few studies of sex chromosomes
      in systems where such transitions have been documented. The European tadpole
      shrimp, Triops cancriformis, has undergone a transition from dioecy to
      androdioecy (a sexual system where hermaphrodites and males coexist), offering an
      excellent opportunity to test the impact of this transition on the evolution of
      sex chromosomes. To identify sex-linked markers, to understand mechanisms of sex
      determination and to investigate differences between sexual systems, we carried
      out a genome-wide association study using restriction site-associated DNA
      sequencing (RAD-seq) of 47 males, females and hermaphrodites from one dioecious
      and one androdioecious population. We analysed 22.9 Gb of paired-end sequences
      and identified and scored >3000 high coverage novel genomic RAD markers. Presence
      absence of markers, single-nucleotide polymorphism association and read depth
      identified 52 candidate sex-linked markers. We show that sex is genetically
      determined in T. cancriformis, with a ZW system conserved across dioecious and
      androdioecious populations and that hermaphrodites have likely evolved from
      females. We also show that the structure of the sex chromosomes differs
      strikingly, with a larger sex-linked region in the dioecious population compared
      with the androdioecious population. 

PMID- 25757407
TI  - Large-scale genotyping of highly polymorphic loci by next-generation sequencing:
      how to overcome the challenges to reliably genotype individuals?
AB  - Studying the different roles of adaptive genes is still a challenge in
      evolutionary ecology and requires reliable genotyping of large numbers of
      individuals. Next-generation sequencing (NGS) techniques enable such large-scale
      sequencing, but stringent data processing is required. Here, we develop an easy
      to use methodology to process amplicon-based NGS data and we apply this
      methodology to reliably genotype four major histocompatibility complex (MHC) loci
      belonging to MHC class I and II of Alpine marmots (Marmota marmota). Our post
      processing methodology allowed us to increase the number of retained reads. The
      quality of genotype assignment was further assessed using three independent
      validation procedures. A total of 3069 high-quality MHC genotypes were obtained
      at four MHC loci for 863 Alpine marmots with a genotype assignment error rate
      estimated as 0.21%. The proposed methodology could be applied to any genetic
      system and any organism, except when extensive copy-number variation occurs (that
      is, genes with a variable number of copies in the genotype of an individual). Our
      results highlight the potential of amplicon-based NGS techniques combined with
      adequate post-processing to obtain the large-scale highly reliable genotypes
      needed to understand the evolution of highly polymorphic functional genes. 

PMID- 25757408
TI  - Knowledge and attitudes of Brazilian dental students and dentists regarding
      bisphosphonate-related osteonecrosis of the jaw.
AB  - PURPOSE: The aim of this study was to evaluate the knowledge of Brazilian
      dentists (DEN) and dental students (DS) about bisphosphonates (BP) and
      bisphosphonate-related osteonecrosis of the jaw (BRONJ). METHODS: A convenience
      sample of 104 DEN and 100 DS was randomly selected and invited to answer a
      questionnaire. The questionnaire was structured on the basis of the main
      information about BP and the risk factors associated with the development of
      BRONJ. The data obtained were analyzed by the chi-square and Fisher's exact
      tests, considering significance of 5%. RESULTS: Seventy-five (72.1%) DEN and 75
      (75%) DS did not know the BP cited in the questionnaire (p < 0.0001), and their
      commercial brand names were not recognized by 88 (84.6%) DEN and 86 (86%) DS (p <
      0.0001). In the same way, 62 (59.6%) DEN (p = 0.04) and 58 (58%) DS (p < 0.0001)
      did not recognize BRONJ as an oral side effect of BP or point out oral conditions
      that were not associated with the use of BP. CONCLUSIONS: Practical initiatives,
      such as free lectures and workshops, must be taken to broaden the knowledge of
      DEN and DS about BP and thus contribute to the prevention of BRONJ.

PMID- 25757409
TI  - Adrenal renal fusion confusion: a case report of an adrenal cortical adenoma with
      adrenal-renal fusion.
AB  - We report a case of laminaria hypersensitivity treated with diphenhydramine and
      corticosteroids. A literature review identified 10 previously reported cases,
      with 8 recognized as anaphylaxis, and good outcomes with corticosteroids and
      antihistamines despite limited epinephrine utilization. Laminaria
      hypersensitivity is likely IgE mediated with an increased anaphylaxis risk with
      prior exposure. 

PMID- 25757410
TI  - Outcome of open massive rotator cuff repairs with double-row suture knotless
      anchors: case series.
AB  - PURPOSE: The aim of the present study was to evaluate functional and quality of
      life outcomes after transosseous equivalent (TOE) double row suture technique for
      massive rotator cuff (RTC) tear repair using validated subjective and objective
      measures. This technique has shown promising preliminary results in RTC repair;
      however, a paucity of evidence regarding these outcomes in massive RTC (MRTC)
      tear repair exists. METHODS: Patients were identified using the Hospital
      Inpatient Enquiry Scheme. Pre-operative MRI and medical records were reviewed. A
      massive RTC tear was defined as the detachment of two or more tendons from their
      point of insertion on the humeral head. The Constant and Oxford Shoulder Scores
      (OSS) and SF-12 questionnaire were used for evaluation. RESULTS: Twenty-two
      patients were studied (72.7 % male; mean age at surgery, 62.6 years). Mean follow
      up was 14 (range six to 30) months. At six weeks postoperatively, 68 % achieved
      good or excellent shoulder function as measured by the OSS and Constant score.
      The cohort's mean SF-12 physical and emotional scores were significantly lower (p
      = 0.0002 and 0.037) and the vitality and mental health scores were higher (p =
      0.005 and 0.006) than the reference norm scores. CONCLUSIONS: The TOE double row
      surgical repair for MRTC tears provides good to excellent functional outcomes and
      is associated with high vitality and mental health scores at a mean of 14 months.
      Physical and emotional scores were lower than reference norm. These results
      suggest this repair technique is appropriate for massive rotator cuff tears, and
      future randomised control studies are warranted.

PMID- 25757411
TI  - Reduced levels of mesenchymal stem cells at the tendon-bone interface tuberosity
      in patients with symptomatic rotator cuff tear.
AB  - PURPOSE: While the use of bone marrow concentrate (BMC) has been described in the
      treatment of rotator cuff tears, the impact of a rotator cuff injury on the
      mesenchymal stem cells (MSCs) content present in the human shoulder has not been
      determined, especially with regard to changes in the levels of MSCs at the tendon
      bone interface. With the hypothesis that there was a decreased level of MSCs at
      the tendon-bone interface tuberosity in patients with rotator cuff tear, we
      assessed the level of MSCs in the tuberosity of the shoulder of patients
      undergoing a rotator cuff repair. METHODS: We analysed the data of 125 patients
      with symptomatic rotator cuff tears and of 75 control patients without rotator
      cuff injury. We recorded the following data: size of tear, number of torn
      tendons, aetiology of the tear, lag time between onset of shoulder
      symptoms/injury and repair, and also fatty infiltration of muscles. Mesenchymal
      stem cell content at the tendon-bone interface tuberosity was evaluated by bone
      marrow aspiration collected in the humeral tuberosities of patients at the
      beginning of surgery. RESULTS: A significant reduction in MSC content (from
      moderate, 30-50 %, to severe >70 %) at the tendon-bone interface tuberosity
      relative to the MSC content of the control was observed in all rotator cuff
      repair study patients. Severity of the decrease was statistically correlated to a
      number of factors, including the delay between onset of symptoms and surgery,
      number of involved tendons, fatty infiltration stage and increasing patient age.
      CONCLUSION: This study demonstrates that the level of MSCs present in the greater
      tuberosity of patients with a rotator cuff tear decreases as a function of a
      number of clinical factors, including lag time from tear onset to treatment, tear
      size, number of tears and stage of fatty infiltration, among others. This
      information may help the practices in using biologic augmentation of a rotator
      cuff repair.

PMID- 25757412
TI  - Variation in type of adjuvant chemotherapy received among patients with stage I
      breast cancer: A multi-institutional study.
AB  - BACKGROUND: Among patients with stage I breast cancer, there is significant
      uncertainty concerning the optimal threshold at which to consider chemotherapy,
      and when considered, there is controversy regarding whether to consider non
      intensive versus intensive regimens. The authors examined the types and costs of
      adjuvant chemotherapy received among patients with stage I breast cancer.
      METHODS: The current study was a prospective cohort study including patients with
      stage I breast cancer who were treated at a National Comprehensive Cancer Network
      center from 2000 through 2009. Stage was defined according to the version of the
      American Joint Committee on Cancer Staging Manual applicable at the time of
      diagnosis. Stratifying by human epidermal growth factor receptor 2 (HER2), the
      authors examined the percentage of patients receiving intensive versus non
      intensive chemotherapy regimens and the factors associated with type of
      chemotherapy administered using multivariable logistic regression. Costs of the
      most common regimens were estimated. RESULTS: Of 8907 patients, 33% received
      adjuvant chemotherapy. Among those individuals, there was an increase in the use
      of intensive chemotherapy within the last decade, from 31% in 2000 through 2005
      to 63% in 2008 through 2009 (including an increase in the use of the combination
      of docetaxel, carboplatin, and trastuzumab) among patients with HER2-positive
      disease and from 15% in 2000 through 2005 to 41% in 2008 through 2009 among
      patients with HER2-negative disease (32% of patients with hormone receptor
      positive and 59% of patients with triple-negative disease). Among patients
      treated with non-intensive regimens, there was an increase in the use of the
      combination of docetaxel and cyclophosphamide noted, with a decrease in the use
      of the doxorubicin and cyclophosphamide combination. The choice of regimen varied
      significantly by institution. The major drivers of cost variation were the
      incorporation of biologics (eg, trastuzumab) and growth factors, with significant
      variation even within non-intensive and intensive regimens. CONCLUSIONS: Over
      time, there was an increase in use of intensive regimens among Stage I breast
      cancer, with striking institutional and cost variations.

PMID- 25757413
TI  - Bandgap engineering of coal-derived graphene quantum dots.
AB  - Bandgaps of photoluminescent graphene quantum dots (GQDs) synthesized from
      anthracite have been engineered by controlling the size of GQDs in two ways:
      either chemical oxidative treatment and separation by cross-flow ultrafiltration,
      or by a facile one-step chemical synthesis using successively higher temperatures
      to render smaller GQDs. Using these methods, GQDs were synthesized with tailored
      sizes and bandgaps. The GQDs emit light from blue-green (2.9 eV) to orange-red
      (2.05 eV), depending on size, functionalities and defects. These findings provide
      a deeper insight into the nature of coal-derived GQDs and demonstrate a scalable
      method for production of GQDs with the desired bandgaps. 

PMID- 25757414
TI  - The best nanoparticle size distribution for minimum thermal conductivity.
AB  - Which sizes of nanoparticles embedded in a crystalline solid yield the lowest
      thermal conductivity? Nanoparticles have long been demonstrated to reduce the
      thermal conductivity of crystals by scattering phonons, but most previous works
      assumed the nanoparticles to have a single size. Here, we use optimization
      methods to show that the best nanoparticle size distribution to scatter the broad
      thermal phonon spectrum is not a similarly broad distribution but rather several
      discrete peaks at well-chosen nanoparticle radii. For SiGe, the best size
      distribution yields a thermal conductivity below that of amorphous silicon.
      Further, we demonstrate that a simplified distribution yields nearly the same low
      thermal conductivity and can be readily fabricated. Our work provides important
      insights into how to manipulate the full spectrum of phonons and will guide the
      design of more efficient thermoelectric materials. 

PMID- 25757415
TI  - Genome instability: Targeted telomere insertion.

PMID- 25757418
TI  - When detainees have a disability: Their rights and fundamental freedoms.
AB  - This article describes and clarifies the human rights of persons with
      disabilities in the context of detention in light of the recently adopted and
      already in force Convention on the Rights of Persons with Disabilities (the
      Convention). Focusing on the Convention, the article sheds light on the legality
      of certain forms of detention affecting persons with disabilities, the
      substantive and procedural requirements for their detention, and on their rights
      in relation to conditions of detention. This article also provides an account of
      the different treatments and practices inflicted on persons with disabilities in
      prisons and other institutions and assesses whether they constitute torture and
      ill treatment. The authors argue that the Convention on the Rights of Persons
      with Disabilities represents a paradigm shift that requires States to modify and
      adopt laws, policies and practices that fully respect the right to liberty of
      persons with disabilities, and their equal enjoyment of rights while in
      detention, including the right to be free from torture and ill treatment. 

PMID- 25757416
TI  - Three-dimensional genome architecture: players and mechanisms.
AB  - The different cell types of an organism share the same DNA, but during cell
      differentiation their genomes undergo diverse structural and organizational
      changes that affect gene expression and other cellular functions. These can range
      from large-scale folding of whole chromosomes or of smaller genomic regions, to
      the re-organization of local interactions between enhancers and promoters,
      mediated by the binding of transcription factors and chromatin looping. The
      higher-order organization of chromatin is also influenced by the specificity of
      the contacts that it makes with nuclear structures such as the lamina.
      Sophisticated methods for mapping chromatin contacts are generating genome-wide
      data that provide deep insights into the formation of chromatin interactions, and
      into their roles in the organization and function of the eukaryotic cell nucleus.

PMID- 25757417
TI  - Sumoylation of CCAAT/enhancer-binding protein alpha is implicated in
      hematopoietic stem/progenitor cell development through regulating runx1 in
      zebrafish.
AB  - The small ubiquitin-related modifier (SUMO) participates in various cellular
      processes, including maintenance of genome integrity, nuclear transport,
      transcription and signal transduction. However, the biological function of
      sumoylation in hematopoiesis has not been fully explored. We show here that
      definitive hematopoietic stem/progenitor cells (HSPCs) are depleted in SUMO
      deficient zebrafish embryos. Impairment of sumoylation attenuates HSPC generation
      and proliferation. The hyposumoylation triggered HSPC defects are CCAAT/enhancer
      binding protein alpha (C/ebpalpha) dependent. Critically, a SUMO-C/ebpalpha
      fusion rescues the defective hematopoiesis in SUMO-deficient embryos, at least in
      part through restored runx1 expression. While C/ebpalpha-dependent transcription
      is involved in myeloid differentiation, our studies here reveal that C/ebpalpha
      sumoylation is essential for HSPC development during definitive hematopoiesis. 

PMID- 25757419
TI  - Mental health in prisons: A public health agenda.
AB  - Mental illness affects the majority of prisoners. Mental health issues are
      beginning to take a central position in the development of prison health
      services, reflecting this burden of disease. This change in focus is not before
      time. But prison mental health services cannot exist in isolation. Public health
      systems should lead provision of care for patients with acute and severe illness.
      A whole prison approach to health and, specifically, mental health will offer the
      greatest likelihood that offenders will thrive, benefit from imprisonment, and
      lead law-abiding lives after release. Public awareness of the scale and
      commitment of prisons to mental health and illness, and understanding of prisons'
      role in society, are necessary developments that would protect and enhance public
      mental health, as well as creating a healthier and safer society. This article
      draws on recent reviews, information and statements to set out a public health
      agenda for mental health in prisons. 

PMID- 25757420
TI  - No One Knows: Offenders with learning disabilities and learning difficulties.
AB  - No One Knows is concerned about people with learning disabilities and
      difficulties who get into trouble with the police and who enter the criminal
      justice system. The terms 'learning difficulties' and 'learning difficulties' are
      often used interchangeably to describe people with an intellectual disability,
      excluding those who, for example, have dyslexia or Asperger syndrome. No One
      Knows, however, has adopted a more inclusive approach and has included in its
      remit offenders with learning disabilities as defined by the World Health
      Organization as well as those with a broader range of learning difficulties.
      Although there is some discrepancy on prevalence, it is clear that high numbers
      of people with learning disabilities and difficulties are caught up in the
      criminal justice system. Once in the criminal justice system it is unlikely that
      an individual with learning disabilities or difficulties will be identified or
      that their support needs will be met. This causes difficulties for the individual
      concerned and for the staff who work with them, who receive little or no training
      for working with this group of people. The question of whether people with
      learning disabilities (meaning intellectual disabilities) should be diverted from
      the criminal justice system is considered. 

PMID- 25757421
TI  - 'Hearing Voices': Punishing women's mental ill-health in Northern Ireland's
      jails.
AB  - Informed by primary interviews and observational research conducted by the
      authors with women prisoners in Northern Ireland, this article focuses on prison
      as an institutional manifestation of women's powerlessness and vulnerability,
      particularly those enduring mental ill-health. It contextualises their
      experiences within continua of violence and 'unsafety'. It also considers
      official responses to critical inspection reports and those of the Northern
      Ireland Human Rights Commission based on the authors' research findings. Finally,
      the primary research demonstrates that three decades on from publication the
      first critical analyses of women's imprisonment, the conditions of gendered
      marginalisation, medicalisation and punishment remain. This is brought into stark
      relief in the punitive regimes imposed on those most vulnerable through mental
      ill-health. 

PMID- 25757422
TI  - Neglecting the mental health of prisoners.
AB  - From first contact with the police to release from prison, people with mental ill
      health who come into conflict with the law often find that their mental health
      needs are neglected while they are under the authority of the criminal justice
      system. In 2008, the Prison Reform Trust surveyed independent monitoring boards
      in England and Wales, asking them to comment on mental health care. Topics
      included the adequacy of court diversion schemes, assessments carried out in
      prison reception units, and preparations to ensure continuity of care upon
      release. The responses documented some of the consequences of neglect in prisons
      in England and Wales. Over half of the boards felt that they frequently saw
      prisoners who were too ill to be in prison. Boards also expressed concerns about
      assessment processes in prison reception areas, which were by no means adequate
      to identify mental health problems. A number of boards stated that, too often,
      people with severe mental illnesses are held in segregation units, where they
      endure an impoverished regime. The boards observed that many prisons lack any
      means of identifying people who have learning disabilities, and often their
      disabilities restrict their capacity to engage fully with the regime. 

PMID- 25757423
TI  - Lord Bradley's review of people with mental health or learning disabilities in
      the criminal justice system in England: All not equal in the eyes of the law?

PMID- 25757424
TI  - Identification of LncRNAs/mRNAs related to endometrium function regulated by
      Homeobox A10 in Ishikawa cells.
AB  - As a well-known transcription factor, Homeobox A10 (HOXA10) regulates a large
      number of downstream target genes, leading to the proper function development of
      endometrium for embryo implantation. The change of HOXA10 gene expression level
      can alter the expressions of many other genes, including coding and noncoding
      transcripts. In our study, mRNA and LncRNA expression profiles screening was
      performed by microarray when the HOXA10 gene expression level increased in
      Ishikawa cells. A total of 907 mRNAs and 1,026 LncRNAs were identified as
      differentially expressed transcripts (Fold Change >=2, P-value <0.05, and Q-value
      <0.05) between HOXA10 overexpressed and control Ishikawa cells. Further analysis
      identified that these mRNAs participated in various biological processes, such as
      blood vessel development, cell adhesion, cell cycle, etc. Also, 14 enhancer-like
      LncRNAs and 108 LincRNAs with their nearby mRNAs were identified as coregulated
      transcripts. Our results showed that the mRNA and LncRNA expression profiles
      differed significantly between the two groups and provided useful information for
      further studying the molecular mechanisms of HOXA10 in endometrium. 

PMID- 25757425
TI  - A molecular catalyst for water oxidation that binds to metal oxide surfaces.
AB  - Molecular catalysts are known for their high activity and tunability, but their
      solubility and limited stability often restrict their use in practical
      applications. Here we describe how a molecular iridium catalyst for water
      oxidation directly and robustly binds to oxide surfaces without the need for any
      external stimulus or additional linking groups. On conductive electrode surfaces,
      this heterogenized molecular catalyst oxidizes water with low overpotential, high
      turnover frequency and minimal degradation. Spectroscopic and electrochemical
      studies show that it does not decompose into iridium oxide, thus preserving its
      molecular identity, and that it is capable of sustaining high activity towards
      water oxidation with stability comparable to state-of-the-art bulk metal oxide
      catalysts. 

PMID- 25757426
TI  - VHR/DUSP3 phosphatase: structure, function and regulation.
AB  - Vaccinia H1-related (VHR) phosphatase, also known as dual-specificity phosphatase
      (DUSP) 3, is a small member of the DUSP (also called DSP) family of phosphatases.
      VHR has a preference for phospho-tyrosine substrates, and has important roles in
      cellular signaling ranging from cell-cycle regulation and the DNA damage response
      to MAPK signaling, platelet activation and angiogenesis. VHR/DUSP3 has been
      implicated in several human cancers, where its tumor-suppressing and -promoting
      properties have been described. We give a detailed overview of VHR/DUSP3
      phosphatase and compare it with its most closely related phosphatases DUSP13B,
      DUSP26 and DUSP27.

PMID- 25757427
TI  - Treatable causes of cerebellar ataxia.
AB  - The cerebellar ataxia syndromes are a heterogeneous group of disorders clinically
      characterized by the presence of cerebellar dysfunction. Initial assessment of
      patients with progressive cerebellar ataxia is complex because of an extensive
      list of potential diagnoses. A detailed history and comprehensive examination are
      required for an accurate diagnosis and hierarchical diagnostic investigations.
      Although no cure exists for most of these conditions, a small group of metabolic,
      hereditary, inflammatory, and immune-mediated etiologies of cerebellar ataxia are
      amenable to disease-modifying, targeted therapies. Over the past years, disease
      specific treatments have emerged. Thus, clinicians must become familiar with
      these disorders because maximal therapeutic benefit is only possible when done
      early. In this article, we review disorders in which cerebellar ataxia is a
      prominent clinical feature requiring targeted treatments along with specific
      management recommendations.

PMID- 25757428
TI  - Effect of thermal processing on astaxanthin and astaxanthin esters in pacific
      white shrimp Litopenaeus vannamei.
AB  - The red color of processed shrimp, one of the most attractive attributes and an
      important criterion for consumers, is often limited by thermal processing
      (microwaving, boiling and frying), due to astaxanthin degradation. The effect of
      thermal processing on astaxanthin in Pacific white shrimp (Litopenaeus vannamei)
      were investigated. A High-performance liquid chromatographic - atmospheric
      pressure chemical ionization mass spectrometry (LC-(APCI)-MS/MS) method was used
      to identify and quantify all-trans- and cis-isomers of astaxanthin, and molecular
      species of astaxanthin esters in fresh and thermal processed shrimps. Total
      astaxanthin loss ranged from 7.99% to 52.01% in first 3 min under three thermal
      processing. All-trans-astaxanthin was most affected, with a reduction from 32.81
      to 8.72 MUg kg(-1), while 13-cis-astxanthin had a rise (from 2.38 to 4.58 MUg kg(
      1)). Esterified astaxanthin was shown to hydrolyze and degrade, furthermore
      astaxanthin diesters had a better thermostability compare to astaxanthin
      monoesters. Astaxanthin monoesters with eicosapntemacnioc acid (EPA, C20:5) and
      docosahexaenoic acid (DHA, C22:6), had a lower thermal stability than those with
      saturated fatty acids, however, it was the opposite of astaxanthin diesters. The
      findings suggested that the method of thermal processing should be carefully used
      in the manufacturing and domestic cooking of shrimps. The results also could be
      useful in calculating the dietary intake of astaxanthin and in assessing
      astaxanthin profiles and contents of shrimp containing products. 

PMID- 25757429
TI  - Determination of polar components in frying oils by Fourier-transform near
      infrared spectroscopy.
AB  - A rapid and convenient method was developed to determine the polar components
      (PC) of frying oil by Fourier-transform near-infrared (FTNIR) spectroscopy. One
      hundred twenty six oil samples were used to PC determination by column
      chromatography and FTNIR spectroscopy combined with partial least-square (PLS)
      calibration. The optimal PLS calibration was obtained after the Savitzky-Golay
      smoothing and first derivative treatment performed in the wavelength ranges of
      4963 cm(-1) to 4616 cm(-1), 5222 cm(-1) to 5037 cm(-1), and 5688 cm(-1) to 5499
      cm(-1). The obtained correlation coefficient (R) was 0.998 and the root mean
      square error of calibration was 1.0%. The PLS calibration was validated, and the
      results showed that the highest correlation (R) was 0.997 between reference value
      and the FTNIR predicted value and the root mean square error of prediction was
      1.3%. Therefore, the FTNIR technique can be effectively applied to quantify PC
      with the advantages of simple operation and no pollution. 

PMID- 25757430
TI  - Influence of the fruit's ripeness on virgin olive oil quality.
AB  - Virgin Olive Oil (VOO) is a product much demanded by consumers looking for the
      highest quality and certain traits considered to be typical of the Mediterranean
      area. The olive fruit's properties and the industry-regulated physicochemical and
      sensory parameters of seven cultivars were evaluated during the ripening process.
      In general, the oil percentage in both the wet and dry material increased for all
      the cultivars from the green to the spotted stages of maturation, and they stayed
      constant statistically until the ripe stage with just a few exceptions. The
      lowest oil content was observed in the Manzanilla Cacerena cultivar in all stages
      of maturation. The cultivars that presented the lowest oil yields in the Abencor
      system were Manzanilla Cacerena and Carrasquena, and the highest Corniche. In
      general, all the cultivars except one presented good behaviour during the mixing
      process, the exception being Manzanilla Cacerena which presented the lowest
      values of the extractability percentage. The moisture content of the olives
      presented a common pattern, increasing from the green to the spotted stage, with
      the differences being significant in the Corniche, Picual, and Verdial de Badajoz
      cultivars. All the oils analysed were classified into the "extra virgin" category
      according to the results for the regulated parameters. The fruity, bitter, and
      pungent attributes decreased during ripening in all the cultivars studied. In the
      green stage of maturation, Arbequina had the least intensity of bitterness and
      pungency, but there were no significant differences among cultivars in the fruity
      attribute. 

PMID- 25757431
TI  - Enzymatic preparation of human milk fat substitutes and their oxidation
      stability.
AB  - Human milk fat substitutes (HMFSs), rich in palmitic acid (P) at the sn-2
      position of triacylglycerol (TAG), were prepared from lard via Novozym435((r))-
      and Lipozyme RM-IM((r))-mediated two-step reactions. First, 2-palmitoyl
      monoacylglycerol (2-P-MAG, 90% purity) was prepared via Novozym435((r))mediated
      ethanolysis of lard. Then, 2-P-MAG, oleic acid (O), linoleic acid (L), and lard
      were dissolved in hexane and subjected to a Lipozyme RM-IM((r))-mediated reaction
      for HMFS preparation. The effect of the amount of 2-P-MAG and fatty acids (O and
      L) in HMFS preparation were investigated. Under the optimum reaction conditions:
      7 mmol of lard, 3.0 mmol of 2-P-MAG, 5.2 mmol of O, 3.5 mmol of L, 10 mL of
      hexane, 10 wt% of Lipozyme RM-IMR((r)) (against the total weight of substrates),
      550 rpm, 37 degrees C and 6 h, a HMFS with total fatty acid composition and P
      content at the sn-2 position of TAG similar to that of human milk fat was
      prepared. In the same way, a HMFS having polyunsaturated fatty acids (PUFA) such
      as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) (PUFA-HMFS) was
      prepared. The HMFS and PUFA-HMFS prepared in this study, as well as fats
      extracted from commercially available powdered milk for infants (FPM) were
      evaluated for their oxidation stability by an auto-oxidation test. The test
      showed HMFS and PUFA-HMFS to possess greater oxidation stability than that the
      FPMs. These results indicated that the HMFS and PUFA-HMFS prepared in this study
      have value as potential ingredients for powdered milk. 

PMID- 25757432
TI  - Palmitoleic acid calcium salt: a lubricant and bactericidal powder from natural
      lipids.
AB  - Palmitoleic acid is a promising bactericidal agent for cleansing products with
      alternative bactericidal abilities. In this study, we focus on the physical and
      biological activity of palmitoleic acid calcium salt (C16:1 fatty acid Ca salt)
      because it forms via an ion-exchange reaction between palmitoleic acid and Ca
      ions in tap water, and remains on the skin surface during the cleansing process.
      Here, we prepared C16:1 fatty acid Ca salt to investigate its crystal structure
      and physical and bactericidal properties. The Ca salt was a plate-shaped lamellar
      crystalline powder with a particle diameter of several micrometers to several
      tens of micrometers; it exhibited significant lubricity and alternative
      bactericidal activity against Staphylococcus aureus (S. aureus) and
      Propionibacterium acnes (P. acnes). We also examined other fatty acid Ca salts
      prepared from lauric acid (C12:0 fatty acid), palmitic acid (C16:0 fatty acid),
      and oleic acid (C18:1 fatty acid). The bactericidal activities and lubricity of
      the fatty acid Ca salts changed with the alkyl chain length and the degree of
      unsaturation. The C16:1 fatty acid Ca salt exhibited the strongest selective
      bactericidal ability among the four investigated fatty acid Ca salts. These
      findings suggest that C16:1 fatty acid and its Ca salt have potential
      applications in cleansing and cosmetic products. 

PMID- 25757433
TI  - In vitro antibacterial and chemical properties of essential oils including native
      plants from Brazil against pathogenic and resistant bacteria.
AB  - The antimicrobials products from plants have increased in importance due to the
      therapeutic potential in the treatment of infectious diseases. Therefore, we
      aimed to examine the chemical characterisation (GC-MS) of essential oils (EO)
      from seven plants and measure antibacterial activities against bacterial strains
      isolated from clinical human specimens (methicillin-resistant Staphylococcus
      aureus (MRSA) and sensitive (MSSA), Escherichia coli, Pseudomonas aeruginosa,
      Salmonella Typhimurium) and foods (Salmonella Enteritidis). Assays were performed
      using the minimal inhibitory concentration (MIC and MIC90%) (mg/mL) by agar
      dilution and time kill curve methods (log CFU/mL) to aiming synergism between EO.
      EO chemical analysis showed a predominance of terpenes and its derivatives. The
      highest antibacterial activities were with Cinnamomun zeylanicum (0.25 mg/mL on
      almost bacteria tested) and Caryophyllus aromaticus EO (2.40 mg/mL on Salmonella
      Enteritidis), and the lowest activity was with Eugenia uniflora (from 50.80 mg/mL
      against MSSA to 92.40 mg/mL against both Salmonella sources and P. aeruginosa)
      EO. The time kill curve assays revealed the occurrence of bactericide synergism
      in combinations of C. aromaticus and C. zeylanicum with Rosmarinus. officinalis.
      Thus, the antibacterial activities of the EO were large and this can also be
      explained by complex chemical composition of the oils tested in this study and
      the synergistic effect of these EO, yet requires further investigation because
      these interactions between the various chemical compounds can increase or reduce
      (antagonism effect) the inhibitory effect of essential oils against bacterial
      strains. 

PMID- 25757434
TI  - Bioactivity of essential oil from Artemisia stolonifera (Maxim.) Komar. and its
      main compounds against two stored-product insects.
AB  - Artemisia stolonifera, a perennial herb, is widely distrbuted in China. The aim
      of this study was to analyze the essential oil from the aerial parts of Artemisia
      stolonifera, as well as to evaluate the bioactivity of the oil and its main
      constituents. The essential oil was analyzed by gas chromatography-flame
      ionization detector and gas chromatography-mass spectrometry that allowed
      characterizing 22 compounds. The main components were eucalyptol (32.93%), beta
      pinene (8.18%), camphor (6.12%) and terpinen-4-ol (6.11%), and obtained from the
      essential oil after a further isolation. During the contact toxicity tests, the
      essential oil (LD50 = 8.60 MUg/adult) exhibited stronger toxicity against
      Tribolium castaneum adults than those isolated constituents, however, camphor and
      terpinen-4-ol showed 1 and 2 times toxicity against Lasioderma serricorne adults
      than the essential oil (LD50 = 12.68 MUg/adult) with LD50 values of 11.30 and
      5.42 MUg/adult, respectively. In the fumigant toxicity tests, especially on
      Tribolium castaneum, the essential oil (LC50 = 1.86 mg/L air) showed almost the
      same level toxicity as positive control, methyl bromide (LC50 = 1.75 mg/L air).
      Moreover, the essential oil and its four isolated constituents also exhibited
      strong repellency against two stored-product insects. 

PMID- 25757435
TI  - DPPH scavenging, PRAP activities and essential oil composition of edible Lathyrus
      ochrus L. (Cyprus Vetch, Luvana) from Cyprus.
AB  - The essential oil of the aerial parts of edible Lathyrus ochrus L. was
      investigated by simultaneous GC, GC/MS analyses under the same conditions. Trace
      amount of oil (0.01> mL) obtained by hydro distillation of 200 g fresh plants was
      trapped in 1 mL n-hexane. Twenty components were detected representing 91.55 +/-
      0.56 % of the oil. The main components were phytol 49.39 +/- 0.44 %, hexadecanoic
      acid 20.64 +/- 0.89 % and pentacosane 4.20 +/- 0.09 %. Essential oil solution (1%
      oil: n-hexane) afforded similar DPPH scavenging activity (9.28 +/- 1.30 %) when
      compared with positive controls alpha-tocopherol (9.74 +/- 0.21 %) and BHT (7.79
      +/- 0.26 %) at the same concentrations. Antioxidant activity of the oil was
      determined using a new HPTLC-PRAP assay. The oil afforded two fold higher
      reducing activity of phosphomolybdenum complex (594.85 +/- 5.14 AU) when compared
      with positive controls alpha- tocopherol (271.10 +/- 2.86 AU) and BHT (210.53 +/-
      1.81 AU) at the same concentration. 

PMID- 25757436
TI  - Castor oil as secondary carbon source for production of sophorolipids using
      Starmerella bombicola NRRL Y-17069.
AB  - Sophorolipids (SLs), a prominent member of the biosurfactants family are produced
      in acidic and/or lactonic form by yeast Starmerella bombicola NRRL Y-17069 when
      grown on hydrophilic or hydrophobic or both carbon sources. In current study,
      ricinoleic acid rich castor oil (10%) was used as hydrophobic and glycerol (10%)
      was used as hydrophilic carbon source. The yields of 24.5 +/- 0.25 g/l
      sophorolipids were analyzed by anthrone and HPLC method which further increased
      upto 40.24 +/- 0.76 g/l sophorolipids using fed batch process at 5L fermenter
      level. The structures of sophorolipids synthesized on castor oil were elucidated
      by liquid chromatography-mass spectrometer (LC-MS), (13)C and (1)H NMR. The
      results indicated that the ricinoleic acid (RA) gets hydroxylated at omega-1
      position but incorporated into sophorolipids through already available hydroxyl
      group at 12(th) position. It resulted in the production of a novel sophorolipids
      with hydroxyl fatty acid as side chain and has applications as surfactant for
      novel drug delivery, anti microbial agent, cosmetic ingredient and emulsifier. 

PMID- 25757437
TI  - Effect of plant growth regulators on fatty acids composition in Jatropha curcas
      L. callus culture.
AB  - The influence of Naphtaleneacetic acid (NAA) and 6-Benzylaminopurine (BAP) on
      callus formation, its morphology and fatty acids profile were examined from
      Jatropha curcas L. Embryo from seeds of J. curcas L. were sown in Murashige and
      skoog (MS) medium with NAA and BAP. All treatments induced callus formation,
      however callus morphology was different in most of the treatments. Higher callus
      biomass was presented with 1.0 NAA + 0.5 BAP mg/L. Plant growth regulators
      modifies the fatty acids profile in callus of J. curcas L. BAP was induced
      linoleic and linolenic acids. 

PMID- 25757438
TI  - Changes in plasma glucose in Otsuka Long-Evans Tokushima Fatty rats after oral
      administration of maple syrup.
AB  - We investigate whether maple syrup is a suitable sweetener in the management of
      type 2 diabetes using the Otsuka Long-Evans Tokushima Fatty (OLETF) rat. The
      enhancement in plasma glucose (PG) and glucose absorption in the small intestine
      were lower after the oral administration of maple syrup than after sucrose
      administration in OLETF rats, and no significant differences were observed in
      insulin levels. These data suggested that maple syrup might inhibit the
      absorption of glucose from the small intestine and preventing the enhancement of
      PG in OLETF rats. Therefore, maple syrup might help in the prevention of type 2
      diabetes. 

PMID- 25757439
TI  - Topical therapies for rheumatoid arthritis by gel ointments containing
      indomethacin nanoparticles in adjuvant-induced arthritis rat.
AB  - Indomethacin (IMC), a nonsteroidal anti-inflammatory drug, has been used in the
      treatment of rheumatoid arthritis (RA), although its clinical use has been
      limited by its systemic side effects that include gastrointestinal lesions.
      Therefore, the development of IMC formulations that do not cause gastrointestinal
      lesions is highly anticipated. In this study, we designed new topical
      formulations containing IMC solid nanoparticles (IMCnano gel ointment), and
      investigated their pharmacokinetics. In addition, we demonstrate the preventive
      effects of this topical application of IMC nanoparticles on inflammation in
      adjuvant-induced arthritis rat (AA rat). The IMCnano gel ointment was prepared
      using Bead Smash 12 (a bead mill) and additives including 2-hydroxypropyl-beta
      cyclodextrin, methylcellulose and Carbopol 934; the mean particle size of the IMC
      nanoparticles was 173 +/- 91 nm (means +/- S.D.). The application of the IMCnano
      gel ointment attenuated the increase in paw edema of the hind feet of AA rats in
      comparison with AA rats treated with gel ointment containing IMC microparticles
      (IMCmicro gel ointment, particle diameter 17.1 +/- 11.6 mm, means +/- S.D). In
      addition, the accumulation of IMC from the IMCnano gel ointment in skin tissue
      was significantly large than for the IMCmicro gel ointment; however, the plasma
      IMC concentrations were similar for the IMCmicro and IMCnano gel ointments. Our
      findings suggest that the dermal application of nanoparticles may enable a
      medication to be applied without high-systemic drug levels, which could provide
      efficient and effective therapy that spares patients from unwanted side effects.
      A formulation of a topical drug delivery system using IMC nanoparticles may
      provide a delivery option for the clinical treatment of RA. 

PMID- 25757440
TI  - 1-Aza-15-Crown-5 Functionalized Graphene Oxide for 2D Graphene-Based Li+-ion
      Conductor.
AB  - Attachment of Li(+) ion on graphene surface to realize Li(+)-ion conductor is a
      real challenge because of the weak interaction between the ions and the
      functional groups of graphene oxide; although, a large number of theoretical
      results are already available in the literature. To overcome this problem,
      graphene oxide is functionalized by 1-aza-15-crown-5, the cage-like structure
      containing four oxygens that can bind Li(+) ion through electrostatic
      interaction. Li(+) migration on graphene surface has been investigated using ac
      relaxation mechanism. Perfect Debye-type relaxation behavior with beta
      (relaxation exponent) value ~1 resulting from single ion is observed. The
      activation energy of Li(+) migration arising due to cation-pi interaction is
      found to be 0.37 eV, which agrees well with recently reported theoretical value.
      It is believed that this study will help to design isolated ion conductors for
      Li(+)-ion battery.

PMID- 25757441
TI  - Effect of mesoscale ordering on the density of States of polymeric
      semiconductors.
AB  - A multiscale simulation scheme, which incorporates both long-range conformational
      disorder and local molecular ordering, is proposed for predicting large-scale
      morphologies and charge transport properties of polymeric semiconductors. Using
      poly(3-hexylthiophene) as an example, it is illustrated how the energy landscape
      and its spatial correlations evolve with increasing degree of structural order in
      mesophases with amorphous, uniaxial, and biaxial nematic ordering. It is shown
      that the formation of low-lying energy states in more ordered systems is mostly
      due to larger (on average) conjugation lengths and not due to electrostatic
      interactions. The proposed scheme is general and can be applied to a wide range
      of polymeric organic materials. 

PMID- 25757442
TI  - Sinus of valsalva aneurysms: review of the literature and an update on
      management.
AB  - Sinus of Valsalva aneurysm (SOVA), a congenital or acquired cardiac defect that
      is present in roughly 0.09% of the general population, often presents as an
      incidental finding during cardiac imaging. Although an echocardiogram is the
      standard imaging technique for such findings, cardiac computed tomography
      angiography (CCTA) has been increasingly utilized. If SOVA is diagnosed, CCTA is
      also a useful test for patients who are at low to intermediate risk for coronary
      artery disease (CAD) prior to surgical repair. CCTA can accurately rule out CAD,
      obviating the need for invasive angiography in most cases, which may be more
      risky in SOVA patients because their coronaries may be more difficult to engage
      and their aortic root may be more prone to injury. Although surgery has
      previously been the treatment of choice, transcatheter techniques have added to
      the spectrum of nonsurgical alternatives for repair. We report here 4 incidental
      SOVA cases and review the current literature. 

PMID- 25757443
TI  - Breeding on the extreme edge: modulation of the adrenocortical response to acute
      stress in two High Arctic passerines.
AB  - Arctic weather in spring is unpredictable and can also be extreme, so Arctic
      breeding birds must be flexible in their breeding to deal with such variability.
      Unpredictability in weather conditions will only intensify with climate change
      and this in turn could affect reproductive capability of migratory birds.
      Adjustments to coping strategies are therefore crucial, so here we examined the
      plasticity of the adrenocorticotropic stress response in two Arctic songbird
      species-the snow bunting (Plectrophenax nivalis) and Lapland longspur (Calcarius
      lapponicus)-breeding in northwest Greenland. Across the breeding season, the
      stress response was strongest at arrival and least robust during molt in male
      snow buntings. Snow bunting females had higher baseline but similar stress
      induced corticosterone levels compared to males. Modification of the stress
      response was not due to adrenal insensitivity, but likely regulated at the
      anterior pituitary gland. Compared to independent nestlings and adult snow
      buntings, parental-dependent chicks had a more robust stress response. For
      Lapland longspurs, baseline corticosterone was highest at arrival in both male
      and females, and arriving males displayed a higher stress response compared to
      arriving females. Comparison of male corticosterone profiles collected at arrival
      in Greenland (76 degrees N) and Alaska (67-71 degrees N;) reveal that both
      species have higher stress responses at the more northern location. Flexibility
      in the stress response may be typical for birds nesting at the leading edges of
      their range and this ability will become more relevant as global climate change
      results in major shifts of breeding habitat and phenology for migratory birds.

PMID- 25757444
TI  - Evaluation of the diagnostic accuracy of four-view radiography and conventional
      computed tomography analysing sacral and pelvic fractures in dogs.
AB  - OBJECTIVE: The purpose of our study was (1) to determine whether four-view
      radiography of the pelvis is as reliable and accurate as computed tomography (CT)
      in diagnosing sacral and pelvic fractures, in addition to coxofemoral and
      sacroiliac joint subluxation or luxation, and (2) to evaluate the effect of the
      amount of training in reading diagnostic imaging studies on the accuracy of
      diagnosing sacral and pelvic fractures in dogs. METHODS: Sacral and pelvic
      fractures were created in 11 canine cadavers using a lateral impactor. In all
      cadavers, frog-legged ventro-dorsal, lateral, right and left ventro-45 degrees 
      medial to dorsolateral oblique frog leg ("rollover 45-degree view") radiographs
      and a CT of the pelvis were obtained. Two radiologists, two surgeons and two
      veterinary students classified fractures using a confidence scale and noted the
      duration of evaluation for each imaging modality and case. The imaging results
      were compared to gross dissection. RESULTS: All evaluators required significantly
      more time to analyse CT images compared to radiographic images. Sacral and pelvic
      fractures, specifically those of the sacral body, ischiatic table, and the pubic
      bone, were more accurately diagnosed using CT compared to radiography. Fractures
      of the acetabulum and iliac body were diagnosed with similar accuracy (at least
      86%) using either modality. CLINICAL SIGNIFICANCE: Computed tomography is a
      better method for detecting canine sacral and some pelvic fractures compared to
      radiography. Computed tomography provided an accuracy of close to 100% in persons
      trained in evaluating CT images.

PMID- 25757445
TI  - Proximal Roux-en-Y gastric bypass alters drug absorption pattern but not systemic
      exposure of CYP3A4 and P-glycoprotein substrates.
AB  - STUDY OBJECTIVES: To evaluate the effect of Roux-en-Y gastric bypass surgery
      (RYGB) on the pharmacokinetics of midazolam (a CYP3A4 substrate) and digoxin (a P
      glycoprotein substrate). DESIGN: Prospective, nonblinded, longitudinal, single
      dose pharmacokinetic study in three phases: presurgery baseline and postoperative
      assessments at 3 and 12 months. PATIENTS: Twelve obese patients meeting current
      standards for bariatric surgery. MEASUREMENTS AND MAIN RESULTS: At each study
      visit, patients received a single dose of oral digoxin and midazolam at 8 a.m.
      Blood samples were collected at regular intervals for 24 hours after dosing.
      Continuous 12-lead electrocardiogram (EKG), heart rate, blood pressure, and
      respiratory rate were monitored, and pharmacokinetic parameters from the three
      visits were compared. The peak plasma concentration (Cmax ) of midazolam
      increased by 66% and 71% at 3- and 12-month post-RYGB (p=0.017 and p=0.001,
      respectively), whereas the median time to peak concentration (Tmax ) was reduced
      by 50%. The mean Cmax for 1'-hydroxymidazolam increased by 87% and 80% at 3 and
      12 months (p=0.001 and p<0.001, respectively). However, neither the area under
      the concentration-time curve (AUC) for midazolam nor the metabolite-to-parent AUC
      ratio changed significantly over time. For digoxin, the median Tmax decreased
      from 40 minutes at baseline to 30 and 20 minutes at 3 and 12 months,
      respectively. The mean AUC for digoxin, heart rate, and EKG patterns were similar
      across the three study phases. CONCLUSION: Contemporary proximal RYGB increases
      the rate of drug absorption without significantly changing the overall exposure
      to midazolam and digoxin. The Cmax of a CYP3A4 substrate with a high extraction
      ratio was substantially increased after RYGB.

PMID- 25757446
TI  - Can Rectal Diclofenac Prevent Post Endoscopic Retrograde Cholangiopancreatography
      Pancreatitis?
AB  - BACKGROUND: Non steroidal anti-inflammatory drugs (NSAIDs) have been shown to
      reduce the incidence of post endoscopic retrograde cholangiopancreatography
      pancreatitis (PEP). There were various trials using different routes and dosages
      of NSAIDs but meta-analysis revealed inconsistent results. AIMS: The aims of this
      study were to determine the efficacy of rectal diclofenac in preventing PEP and
      to evaluate any adverse events. METHODS: This was a randomized, open-label, two
      arm, prospective clinical trial. Only patients at high risk of developing PEP
      were recruited. They received 100 mg rectal diclofenac or no intervention
      immediately after ERCP. The patients were reviewed 30 days after discharge to
      evaluate any adverse event. RESULTS: Among 144 recruited patients, 69 (47.9%)
      received diclofenac and 75 (52.1%) had no intervention. Eleven patients (7.6%)
      developed PEP, in which seven were from the diclofenac group and four were in the
      control group. Eight cases of PEP (5.5%) were mild and three cases (2.1%) were
      moderate. The differences in pancreatitis incidence and severity between both
      groups were not statistically significant. There were 11 adverse events reported.
      Clinically significant bleeding happened in four patients (2.8%): one from the
      diclofenac group and three from the control group. Other events included
      cholangitis: two patients (2.9%) from the diclofenac group and four (5.3%) from
      the control group. One patient from the diclofenac group (1.4%) had a perforation
      which was treated conservatively. CONCLUSIONS: In summary, prophylactic rectal
      diclofenac did not significantly decrease the incidence of PEP among patients at
      high risk for developing PEP. However, the administration of diclofenac was
      fairly safe with few clinical adverse events.

PMID- 25757447
TI  - Factors Associated with the Quality of Transient Elastography.
AB  - BACKGROUND: Transient elastography is a noninvasive method for the evaluation of
      fibrosis in chronic liver disease. However, its reliability is variable, and the
      factors associated with its accuracy have not been identified completely. AIMS:
      To identify the factors associated with the reliability of transient
      elastography. METHODS: A total of 2033 transient elastography measurements were
      taken from March 2009 to October 2013. Reliability was determined according to
      the interquartile range/median (IQR/M < 0.30 = reliable; IQR/M < 0.10 = very
      reliable). Other indicators such as the percentage of successful measurements
      (>60 %), time of performance, and probe size were recorded. Potential factors
      that could affect the reliability of the procedure were analyzed using
      multivariate logistic regression. RESULTS: Slightly less than 5 % of the
      measurements were unsuccessful, and 83 % of the successful measurements were
      found to be reliable. Factors associated with an unsuccessful measurement were
      female gender, incorrect probe size, and the presence of HCV infection.
      Unreliable measurements were associated with use of the procedure as part of a
      clinical study and success rate. Very reliable evaluations were associated with
      >10 measurements, the presence of chronic hepatic disease, and a success rate of
      >60 %. CONCLUSIONS: The operator and clinical and anthropometric characteristics
      are factors that influence the success and reliability of transient elastography.
      Improvements in the quality of the procedure are needed to provide better
      diagnostic accuracy in clinical practice.

PMID- 25757448
TI  - The Circulating Level of Soluble Receptor for Advanced Glycation End Products
      Displays Different Patterns in Ulcerative Colitis and Crohn's Disease: A Cross
      Sectional Study.
AB  - BACKGROUND: RAGE is a transmembrane receptor expressed on immune and endothelial
      cells, whose binding with its ligands, the S100 calgranulins, leads to chronic
      inflammation. Conversely, its soluble form (sRAGE) plays a protective role by
      acting as a decoy. We carried out a cross-sectional analysis of the sRAGE and
      S100A12 serum levels in patients with Crohn's disease (CD) and ulcerative colitis
      (UC) and searched for a correlation with clinical and biological markers of
      activity. METHODS: We enrolled 60 CD, 67 UC patients, and 66 controls (all
      adults). Disease activity was scored through the clinical, endoscopic, and
      histologic indexes of severity, whilst disease location and behaviour were
      assessed according to the Montreal classification. In all cases, the levels of
      serum sRAGE, S100A12, C-reactive protein, and faecal calprotectin were measured.
      RESULTS: sRAGE levels were significantly lower in UC, both active and inactive,
      than in controls and CD (817.35, range 437.3-1449; 1211, range 843.7-1618;
      1207.5, range 743.15-1875.75; P < 0.05 for both), and inversely correlated with
      clinical and endoscopic indexes of activity in both IBD groups (P < 0.05 for all)
      and with the histologic score in the CD group. Moreover, those CD patients with a
      penetrating behaviour showed a significant reduction in both sRAGE (P = 0.006)
      and S100A12 (P = 0.034) as compared to those with an inflammatory/stricturing
      pattern. Although S100A12 levels were not found up-regulated, a negative
      correlation appeared evident with the clinical (r = -0.38) and endoscopic (r = 
      0.32) indexes of activity in UC and CD, respectively. CONCLUSION: These data
      suggest a different role for RAGE in CD and UC, and a potential use of sRAGE as a
      new biomarker.

PMID- 25757449
TI  - Vitamin D Status Is Associated with Intestinal Inflammation as Measured by Fecal
      Calprotectin in Crohn's Disease in Clinical Remission.
AB  - BACKGROUND: Vitamin D, as potential immune modulator, has been implicated as an
      environmental risk factor for Crohn's disease (CD). Vitamin D status may be
      associated with disease risk, severity, activity, and progression. While
      associations between circulating 25OHD and markers of disease activity and
      inflammation in CD have been reported, the results are inconsistent. AIM: To
      determine the association between vitamin D status and markers of disease
      activity and inflammation in CD. METHODS: One hundred and nineteen CD patients'
      active and inactive diseases were enrolled in the cross-sectional study. Subject
      demographics and clinical data were collected. A serum sample was collected for
      25OHD and CRP analysis, and a stool sample was collected for fecal calprotectin
      (FC) measurement. RESULTS: The mean serum 25OHD concentration of the group was
      59.8 (24.9) nmol/L. After controlling for confounding variables, serum 25OHD
      inversely correlated with FC (r = -0.207, P = 0.030), particularly among those in
      clinical remission (r = -0.242, P = 0.022). The association between FC and 25OHD
      was further confirmed by linear regression (r = 31.3 %, P < 0.001). FC was lower
      in patients with 25OHD levels >=75 nmol/L compared with levels <25 nmol/L [FC:
      32.2 (16.3-98.2) vs 100.0 (34.4-213.5) MUg/g, P = 0.004]. In the current study,
      however, 25OHD was not significantly associated with either CRP or CDAI.
      CONCLUSION: Circulating 25OHD was significantly inversely associated with
      intestinal inflammation as determined by FC in CD. Subgroup analysis confirmed
      the association among those in clinical remission, but not in those with active
      disease. 25OHD was not associated with disease activity score (CDAI) or systemic
      inflammation (CRP). Vitamin D intervention studies are warranted to determine
      whether raising serum 25OHD levels in patients with CD may reduce intestinal
      inflammation as measured by FC.

PMID- 25757450
TI  - Reactors for High Solid Loading Pretreatment of Lignocellulosic Biomass.
AB  - The review summarized the types, the geometry, and the design principle of
      pretreatment reactors at high solid loading of lignocellulose material. Among the
      reactors used, the explosion reactors and the helical stirring reactors are to be
      considered as the practical form for high solids loading pretreatment operation;
      the comminution reactors and the extruder reactors are difficult to be used as an
      independent unit, but possible to be used in the combined form with other types
      of reactors. The principles of the pretreatment reactor design at high solid
      loading were discussed and several basic principles for the design were proposed.
      This review provided useful information for choosing the reactor types and
      designing the geometry of pretreatment operation at the high solids loading.

PMID- 25757452
TI  - Trap density probing on top-gate MoS2 nanosheet field-effect transistors by photo
      excited charge collection spectroscopy.
AB  - Two-dimensional (2D) molybdenum disulfide (MoS2) field-effect transistors (FETs)
      have been extensively studied, but most of the FETs with gate insulators have
      displayed negative threshold voltage values, which indicates the presence of
      interfacial traps both shallow and deep in energy level. Despite such interface
      trap issues, reports on trap densities in MoS2 are quite limited. Here, we probed
      top-gate MoS2 FETs with two- (2L), three- (3L), and four-layer (4L)
      MoS2/dielectric interfaces to quantify deep-level interface trap densities by
      photo-excited charge collection spectroscopy (PECCS), and reported the result
      that deep-level trap densities over 10(12) cm(-2) may exist in the interface and
      bulk MoS2 near the interface. Transfer curve hysteresis and PECCS measurements
      show that shallow traps and deep traps are not that different in density order
      from each other. We conclude that our PECCS analysis distinguishably provides
      valuable information on deep level interface/bulk trap densities in 2D-based
      FETs.

PMID- 25757453
TI  - Arc-melting to narrow the bandgap of oxide semiconductors.
AB  - The bandgap of a series of oxide semiconductors is narrowed by a quick and facile
      arc-melting method. A defective structure is formed in the fast melting and
      cooling process without changing its phase structure. Enhanced optical and
      electrical properties are found in the arc-melted oxide, such as enhanced
      photocatalytic properties of the arc-melted ZnO under visible light. 

PMID- 25757454
TI  - Gelatinases and their tissue inhibitors in a group of subjects with obstructive
      sleep apnea syndrome.
AB  - Obstructive sleep apnea syndrome (OSAS) is associated with an elevated risk of
      cardiovascular events and stroke. Matrix metalloproteinases (MMPs) are
      endopeptidases involved in extracellular matrix degradation and then in the
      development and progression of cardiovascular diseases. Our aim was to evaluate
      plasma levels of gelatinases (MMP-2 and MMP-9) and their tissue inhibitors (TIMP
      1 and TIMP-2) in a group of subjects with OSAS. We enrolled 48 subjects (36 men
      and 12 women; mean age 49.7 +/- 14.68 yrs) with OSAS diagnosed with a 1-night
      cardiorespiratory study and then we subdivided these subjects into two subgroups
      according to the apnea/hypopnea index (AHI): Low (L = 21 subjects with AHI <30)
      and High (H = 27 subjects with AHI >30). We measured plasma concentration of the
      gelatinases and their inhibitors using ELISA kits. We observed a significant
      increase in plasma concentration of MMP-9, MMP-2, TIMP-1 and TIMP-2 in the entire
      group of OSAS subjects and in the two subgroups, with higher levels in the H in
      comparison with the L subgroup. In the whole group of OSAS subjects we also noted
      a significant decrease in MMP-9/TIMP-1 ratio in comparison with normal controls.
      Only MMP-9 was significantly correlated with the severity of the disease,
      expressed as AHI, with the oxygen desaturation index and also with the mean
      oxygen saturation. MMPs pattern is altered in OSAS and significantly influenced
      by the severity of the disease; it probably contributes to the vascular
      remodeling that leads to the atherosclerotic disease and cardiovascular
      complications.

PMID- 25757451
TI  - The Neural Stem Cell Microenvironment: Focusing on Axon Guidance Molecules and
      Myelin-Associated Factors.
AB  - Neural stem cells (NSCs) could produce various cell phenotypes in the
      subventricular zone (SVZ) and dentate gyrus of the hippocampus in the central
      nervous system (CNS), where neurogenesis has been determined to occur. The
      extracellular microenvironment also influences the behaviors of NSCs during
      development and at CNS injury sites. Our previous study indicates that myelin, a
      component of the CNS, could regulate the differentiation of NSCs in vitro. Recent
      reports have implicated three myelin-derived inhibitors, NogoA, myelin-associated
      glycoprotein (MAG), and oligodendrocyte-myelin glycoprotein (OMgp), as well as
      several axon guidance molecules as regulators of NSC survival, proliferation,
      migration, and differentiation. However, the molecular mechanisms underlying the
      behavior of NSCs are not fully understood. In this study, we summarize the
      current literature on the effects of different extrinsic factors on NSCs and
      discuss possible mechanisms, as well as future possible clinical applications. 

PMID- 25757455
TI  - Quantitative dynamic contrast-enhanced ultrasound for the functional evaluation
      of the skeletal muscle microcirculation in systemic sclerosis.
AB  - PURPOSE: The purpose was to evaluate skeletal muscle microcirculation by means of
      quantitative dynamic contrast-enhanced ultrasound (DCEUS) in patients with
      systemic sclerosis (SSc). METHODS: DCEUS imaging of the gastrocnemius muscle was
      performed with phospholipid-stabilized microbubbles filled with sulfur
      hexafluoride in 12 patients with SSc and 12 healthy volunteers. The fitted time
      intensity curves (TIC) during the first 3 minutes after administration of the
      contrast agent bolus were analysed. Time course parameters of the TIC were
      compared between patients and healthy volunteers. RESULTS: Peak enhancement, wash
      in area under the curve and was-out area under the curve was decreased in the
      patient group versus healthy volunteers (168 versus 248 AU p = 0.291; 2193 versus
      3314 p = 0.198; 4948 AU x sec versus 8948 AU x sec p = 0.037). In the SSc
      patients the mean transit time and wash-in perfusion index were numerically, but
      not statistically lower than in the healthy volunteers, but rise and fall time
      were similar. CONCLUSION: On the microvascular level in SSc patients versus their
      healthy counterpart key parameters related to blood volume were decreased and
      perfusion parameters showed a slight diminishment in the patient population.
      These results suggest a component of impaired skeletal muscle microcirculation in
      SSc patients.

PMID- 25757456
TI  - Intertwining Psychiatry Residency Training and Ethics in the College Setting.
AB  - An ethical responsibility exists, currently unaddressed, for mandated psychiatry
      residency training with college student populations. Such training brings
      numerous potential benefits, including exposure to specific disorders and
      administrative structures. As well, individual cases pose ethical dilemmas unique
      to this developmental stage, which segues seamlessly from that of adolescence.
      Relevant case illustrations are employed. Likewise, psychiatric education
      oversight bodies are urged to fulfill their ethical obligations to provide
      pertinent training. 

PMID- 25757457
TI  - Expert consensus panel guidelines on geriatric assessment in oncology.
AB  - Despite consensus guidelines on best practice in the care of older patients with
      cancer, geriatric assessment (GA) has yet to be optimally integrated into the
      field of oncology in most countries. There is a relative lack of consensus in the
      published literature as to the best approach to take, and there is a degree of
      uncertainty as to how integration of geriatric medicine principles might
      optimally predict patient outcomes. The aim of the current study was to obtain
      consensus on GA in oncology to inform the implementation of a geriatric oncology
      programme. A four-round Delphi process was employed. The Delphi method is a
      structured group facilitation process, using multiple iterations to gain
      consensus on a given topic. Consensus was reached on the optimal assessment
      method and interventions required for the commonly employed domains of GA. Other
      aspects of GA, such as screening methods and age cut-off for assessment,
      represented a higher degree of disagreement. The expert panel employed in this
      study clearly identified the criteria that should be included in a clinical
      geriatric oncology programme. In the absence of evidence-based guidelines, this
      may prove useful in the care of older cancer patients. 

PMID- 25757458
TI  - Regulation of intracellular Zn homeostasis in two intestinal epithelial cell
      models at various maturation time points.
AB  - After weaning, piglets are often fed diets supplemented with high concentrations
      of zinc (Zn) to decrease post-weaning diarrhea. The aim of this study was to
      elucidate the regulation of Zn homeostasis within intestinal epithelial cells
      during excessive Zn exposure. High Zn concentrations elevated the intracellular
      Zn level in IPEC-J2 and Caco-2 cells which was influenced by differentiation
      status and time of exposure. With increasing Zn concentrations, mRNA and protein
      levels of metallothionein (MT) and zinc transporter 1 (ZnT1) were upregulated,
      whereas zinc transporter 4 (ZIP4) expression was downregulated. Metal-regulatory
      transcription factor-1 (MTF1) mRNA expression was upregulated at high Zn
      concentrations in IPEC-J2 cells, which corresponded to higher intracellular Zn
      concentrations. Based on these results, we suggest that intestinal epithelial
      cells adapt the expression of these genes to the amount of extracellular Zn
      available in order to maintain Zn homeostasis. Cell line-dependent differences in
      the regulation of Zn homeostasis were detected. 

PMID- 25757459
TI  - Ruthenium-catalyzed C-C coupling of fluorinated alcohols with allenes:
      dehydrogenation at the energetic limit of beta-hydride elimination.
AB  - Ruthenium(II) complexes catalyze the C?C coupling of 1,1-disubstituted allenes
      and fluorinated alcohols to form homoallylic alcohols bearing all-carbon
      quaternary centers with good to complete levels of diastereoselectivity. Whereas
      fluorinated alcohols are relatively abundant and tractable, the corresponding
      aldehydes are often not commercially available because of their instability. 

PMID- 25757460
TI  - Pearls and pitfalls of early obstetric ultrasound in the acute setting.
AB  - First trimester ultrasound is commonly performed to establish dates or evaluate
      early pregnancy complications. With improvement in ultrasound technology,
      visualization of fetal structures has improved. While the emergent evaluation
      does not typically focus on detailed fetal anatomic evaluation (since this is
      typically performed at 18-20 weeks), various fetal structural abnormalities can
      now be visualized, especially during the late first trimester and early second
      trimester. We present a pictorial review of potential pitfalls encountered in
      early obstetric ultrasound with an emphasis on fetal structural abnormalities as
      well as normal fetal anatomy that can be confused with developmental
      abnormalities.

PMID- 25757462
TI  - Information persistence services designed to support home care.
AB  - BACKGROUND: Due to the challenges faced by health and social care systems, in
      particular those related to actual demographic trends, home care emerges as a
      potentially cost-effective solution to answer the needs of citizens, and to allow
      the reallocation of resources to alternatives to hospitalization or
      institutionalization. OBJECTIVE: Home care services require cooperation between
      different actors, including health and social caregivers, care receivers, and
      their informal caregivers (eg, relatives or friends), across time, space, and
      organizational boundaries. Therefore, it is foreseeable that eHealth services can
      contribute to their improvement. The aim of this study is to evaluate information
      persistence services based on the Reference Information Model (RIM) of the Health
      Level Seven (HL7) version 3 to support formal caregivers, both health and social
      care providers, and informal caregivers in the context of home care services.
      METHODS: A pilot study was set up involving two Portuguese institutions that
      provide home care services for the elderly. Defining of information requirements
      was performed according to a comprehensive process. This included a review of the
      literature, observations of work activities, interviews with caregivers, care
      receivers and their relatives, analysis of paper documentation related to care
      receivers' histories, health conditions and care plans, and brainstorming groups
      involving specialized professionals. Following this, information objects were
      implemented and validated. RESULTS: The methodological approach, as well as the
      information persistence services, proved to be robust and adequate to specify,
      implement, and validate different types of information objects related to home
      care services for the elderly. This study also reinforces the application of the
      RIM of the HL7 version 3 beyond the strict scope of health care, allowing the
      persistence of not only health care information, but also information related to
      social assistance activities. CONCLUSIONS: This study contributes to the ongoing
      efforts related to the development of eHealth applications to improve the
      cooperation among formal health care and social caregivers, as well as care
      receivers and their informal caregivers.

PMID- 25757461
TI  - A search for protein biomarkers links olfactory signal transduction to social
      immunity.
AB  - BACKGROUND: The Western honey bee (Apis mellifera L.) is a critical component of
      human agriculture through its pollination activities. For years, beekeepers have
      controlled deadly pathogens such as Paenibacillus larvae, Nosema spp. and Varroa
      destructor with antibiotics and pesticides but widespread chemical resistance is
      appearing and most beekeepers would prefer to eliminate or reduce the use of in
      hive chemicals. While such treatments are likely to still be needed, an alternate
      management strategy is to identify and select bees with heritable traits that
      allow them to resist mites and diseases. Breeding such bees is difficult as the
      tests involved to identify disease-resistance are complicated, time-consuming,
      expensive and can misidentify desirable genotypes. Additionally, we do not yet
      fully understand the mechanisms behind social immunity. Here we have set out to
      discover the molecular mechanism behind hygienic behavior (HB), a trait known to
      confer disease resistance in bees. RESULTS: After confirming that HB could be
      selectively bred for, we correlated measurements of this behavior with protein
      expression over a period of three years, at two geographically distinct sites,
      using several hundred bee colonies. By correlating the expression patterns of
      individual proteins with HB scores, we identified seven putative biomarkers of HB
      that survived stringent control for multiple hypothesis testing. Intriguingly,
      these proteins were all involved in semiochemical sensing (odorant binding
      proteins), nerve signal transmission or signal decay, indicative of the series of
      events required to respond to an olfactory signal from dead or diseased larvae.
      We then used recombinant versions of two odorant-binding proteins to identify the
      classes of ligands that these proteins might be helping bees detect. CONCLUSIONS:
      Our data suggest that neurosensory detection of odors emitted by dead or diseased
      larvae is the likely mechanism behind a complex and important social immunity
      behavior that allows bees to co-exist with pathogens.

PMID- 25757463
TI  - Toll-like receptor 5 deficiency exacerbates cardiac injury and inflammation
      induced by myocardial ischaemia-reperfusion in the mouse.
AB  - Myocardial ischaemia-reperfusion (MIR) triggers a sterile inflammatory response
      important for myocardial healing, but which may also contribute to adverse
      ventricular remodelling. Such inflammation is initiated by molecular danger
      signals released by damaged myocardium, which induce innate immune responses by
      activating toll-like receptors (TLRs). Detrimental roles have been recently
      reported for TLR2, TLR3 and TLR4. The role of other TLRs is unknown. We therefore
      evaluated the role of TLR5, expressed at high level in the heart, in the
      development of myocardial damage and inflammation acutely triggered by MIR. TLR5(
      /-) and wild-type (WT) mice were exposed to MIR (30 min ischaemia, 2 h
      reperfusion). We measured infarct size, markers of cardiac oxidative stress,
      myocardial phosphorylation state of mitogen-activated protein (MAP) kinases and
      AKT, expression levels of chemokines and cytokines in the heart and plasma, as
      well as cardiac function by echography and conductance volumetry. TLR5-deficient
      mice had normal cardiac morphology and function under physiological conditions.
      After MIR, the absence of TLR5 promoted an increase in infarct size and
      myocardial oxidative stress. Lack of TLR5 fostered p38 phosphorylation, reduced
      AKT phosphorylation and markedly increased the expression of inflammatory
      cytokines, whereas it precipitated acute LV (left ventricle) dysfunction.
      Therefore, contrary to the detrimental roles of TLR2, TLR3 and TLR4 in the
      infarcted heart, TLR5 is important to limit myocardial damage, inflammation and
      functional compromise after MIR.

PMID- 25757464
TI  - Child euthanasia: should we just not talk about it?
AB  - Belgium has recently extended its euthanasia legislation to minors, making it the
      first legislation in the world that does not specify any age limit. I consider
      two strands in the opposition to this legislation. First, I identify five
      arguments in the public debate to the effect that euthanasia for minors is
      somehow worse than euthanasia for adults--viz, arguments from weightiness,
      capability of discernment, pressure, sensitivity and sufficient palliative care-
      and show that these arguments are wanting. Second, there is another position in
      the public debate that wishes to keep the current age restriction on the books
      and have ethics boards exercise discretion in euthanasia decisions for minors. I
      interpret this position on the background of Velleman's 'Against the Right to
      Die' and show that, although costs remain substantial, it actually can provide
      some qualified support against extending euthanasia legislation to minors.

PMID- 25757466
TI  - Author's reply to Sharpe.

PMID- 25757468
TI  - New-onset atrial fibrillation is an independent predictor of mortality in medical
      intensive care unit patients.
AB  - BACKGROUND: Atrial fibrillation (AF) has been extensively studied in
      postoperative critically ill surgical patients, but little literature exists to
      describe the outcomes of patients in the medical intensive care unit (ICU).
      OBJECTIVES: To determine the incidence of new-onset AF in patients admitted to a
      medical ICU and if new-onset AF was associated with adverse clinical outcomes.
      METHODS: This was a single-center, retrospective study of all adult patients
      admitted to the medical ICU at an academic medical center for >24 hours between
      December 2008 and April 2010. Collected data included past medical history,
      incidence of new-onset AF, Acute Physiology and Chronic Health Evaluation II
      scores, organ failure, length of stay in the ICU and hospital, and in-hospital
      and 60-day survival. RESULTS: A total of 741 patients were included. New-onset AF
      occurred in 53 patients (7.2%). In-hospital mortality was significantly greater
      for patients with new-onset AF (45% vs 16%; adjusted odds ratio [OR] = 2.21, 95%
      CI 1.07-4.54, P = 0.032), as was 60-day mortality (51% vs 23%; adjusted OR =
      1.99, 95% CI = 1.01-3.91, P = 0.047). Patients with new-onset AF experienced
      greater ICU (6 +/- 10.2 days vs 3 +/- 3.6 days, P < 0.01) and hospital (15 +/- 19
      days vs 7 +/- 9 days, P < 0.01) lengths of stay. CONCLUSIONS: Medical ICU
      patients who developed new-onset AF experienced a 2-fold increase in the odds of
      in-hospital mortality and death at 60 days. Further research investigating
      contributing factors to new-onset AF and potential treatments is warranted.

PMID- 25757467
TI  - Transcriptome profiling of the dynamic life cycle of the scypohozoan jellyfish
      Aurelia aurita.
AB  - BACKGROUND: The moon jellyfish Aurelia aurita is a widespread scyphozoan species
      that forms large seasonal blooms. Here we provide the first comprehensive view of
      the entire complex life of the Aurelia Red Sea strain by employing transcriptomic
      profiling of each stage from planula to mature medusa. RESULTS: A de novo
      transcriptome was assembled from Illumina RNA-Seq data generated from six stages
      throughout the Aurelia life cycle. Transcript expression profiling yielded
      clusters of annotated transcripts with functions related to each specific life
      cycle stage. Free-swimming planulae were found highly enriched for functions
      related to cilia and microtubules, and the drastic morphogenetic process
      undergone by the planula while establishing the future body of the polyp may be
      mediated by specifically expressed Wnt ligands. Specific transcripts related to
      sensory functions were found in the strobila and the ephyra, whereas
      extracellular matrix functions were enriched in the medusa due to high expression
      of transcripts such as collagen, fibrillin and laminin, presumably involved in
      mesoglea development. The CL390-like gene, suggested to act as a strobilation
      hormone, was also highly expressed in the advanced strobila of the Red Sea
      species, and in the medusa stage we identified betaine-homocysteine
      methyltransferase, an enzyme that may play an important part in maintaining
      equilibrium of the medusa's bell. Finally, we identified the transcription
      factors participating in the Aurelia life-cycle and found that 70% of these 487
      identified transcription factors were expressed in a developmental-stage-specific
      manner. CONCLUSIONS: This study provides the first scyphozoan transcriptome
      covering the entire developmental trajectory of the life cycle of Aurelia. It
      highlights the importance of numerous stage-specific transcription factors in
      driving morphological and functional changes throughout this complex
      metamorphosis, and is expected to be a valuable resource to the community.

PMID- 25757469
TI  - Evidence-based strategies to reduce intravenous immunoglobulin-induced headaches.
AB  - OBJECTIVE: To review the literature evaluating pharmacotherapeutic and
      nonpharmacotherapeutic options available to reduce migraines or headaches
      associated with intravenous immunoglobulin (IVIG) treatment. DATA SOURCES: A
      search of MEDLINE (1946 to February 2015) and other secondary resources was
      performed using the terms immunoglobulin, immune globulin, intravenous
      immunoglobulins, migraine, and headache. Other relevant articles referenced from
      the MEDLINE search were also utilized. STUDY SELECTION AND DATA EXTRACTION: Data
      sources were limited to English language clinical trials and case studies. In
      all, 6 clinical studies and 2 case reports met the criteria. DATA SYNTHESIS:
      Headaches or migraines are common adverse effects associated with the
      administration of IVIG. We evaluated 6 clinical studies and 2 case reports
      discussing this adverse event in patients treated with IVIG. Strategies used were
      hydration, switching to an alternate IVIG product, decreased infusion rates, or
      treating with oral analgesics, opioids, propranolol, sumatriptan, or
      dihydroergotamines before, during, or after the IVIG infusion. Overall, the
      majority of patients experienced improvement in headache symptoms, suggesting
      benefit, after using the various strategies discussed. However, the evidence is
      limited to case reports and clinical studies with small sample sizes that do not
      directly measure cause and effect of headache resolution and therapy given in
      those treated with IVIG. CONCLUSIONS: An individualized treatment plan consisting
      of a pharmacotherapy or nonpharmacotherapy strategy used in the literature should
      be recommended after careful consideration of the patient's condition, specific
      IVIG product used, history of migraine, and previously failed and successful
      therapies.

PMID- 25757470
TI  - Mapping the genetic and tissular diversity of 64 phenolic compounds in Citrus
      species using a UPLC-MS approach.
AB  - BACKGROUND AND AIMS: Phenolic compounds contribute to food quality and have
      potential health benefits. Consequently, they are an important target of
      selection for Citrus species. Numerous studies on this subject have revealed new
      molecules, potential biosynthetic pathways and linkage between species. Although
      polyphenol profiles are correlated with gene expression, which is responsive to
      developmental and environmental cues, these factors are not monitored in most
      studies. A better understanding of the biosynthetic pathway and its regulation
      requires more information about environmental conditions, tissue specificity and
      connections between competing sub-pathways. This study proposes a rapid method,
      from sampling to analysis, that allows the quantitation of multiclass phenolic
      compounds across contrasting tissues and cultivars. METHODS: Leaves and fruits of
      11 cultivated citrus of commercial interest were collected from adult trees grown
      in an experimental orchard. Sixty-four phenolic compounds were simultaneously
      quantified by ultra-high-performance liquid chromatography coupled with mass
      spectrometry. KEY RESULTS: Combining data from vegetative tissues with data from
      fruit tissues improved cultivar classification based on polyphenols. The analysis
      of metabolite distribution highlighted the massive accumulation of specific
      phenolic compounds in leaves and the external part of the fruit pericarp, which
      reflects their involvement in plant defence. The overview of the biosynthetic
      pathway obtained confirmed some regulatory steps, for example those catalysed by
      rhamnosyltransferases. The results suggest that three other steps are responsible
      for the different metabolite profiles in 'Clementine' and 'Star Ruby' grapefruit.
      CONCLUSIONS: The method described provides a high-throughput method to study the
      distribution of phenolic compounds across contrasting tissues and cultivars in
      Citrus, and offers the opportunity to investigate their regulation and
      physiological roles. The method was validated in four different tissues and
      allowed the identification and quantitation of 64 phenolic compounds in 20 min,
      which represents an improvement over existing methods of analysing multiclass
      polyphenols.

PMID- 25757471
TI  - Phylogenetic analysis in Myrcia section Aulomyrcia and inferences on plant
      diversity in the Atlantic rainforest.
AB  - BACKGROUND AND AIMS: Myrcia section Aulomyrcia includes ~120 species that are
      endemic to the Neotropics and disjunctly distributed in the moist Amazon and
      Atlantic coastal forests of Brazil. This paper presents the first comprehensive
      phylogenetic study of this group and this phylogeny is used as a basis to
      evaluate recent classification systems and to test alternative hypotheses
      associated with the history of this clade. METHODS: Fifty-three taxa were sampled
      out of the 120 species currently recognized, plus 40 outgroup taxa, for one
      nuclear marker (ribosomal internal transcribed spacer) and four plastid markers
      (psbA-trnH, trnL-trnF, trnQ-rpS16 and ndhF). The relationships were reconstructed
      based on Bayesian and maximum likelihood analyses. Additionally, a likelihood
      approach, 'geographic state speciation and extinction', was used to estimate
      region- dependent rates of speciation, extinction and dispersal, comparing
      historically climatic stable areas (refugia) and unstable areas. KEY RESULTS:
      Maximum likelihood and Bayesian inferences indicate that Myrcia and Marlierea are
      polyphyletic, and the internal groupings recovered are characterized by
      combinations of morphological characters. Phylogenetic relationships support a
      link between Amazonian and north-eastern species and between north-eastern and
      south-eastern species. Lower extinction rates within glacial refugia suggest that
      these areas were important in maintaining diversity in the Atlantic forest
      biodiversity hotspot. CONCLUSIONS: This study provides a robust phylogenetic
      framework to address important ecological questions for Myrcia s.l. within an
      evolutionary context, and supports the need to unite taxonomically the two
      traditional genera Myrcia and Marlierea in an expanded Myrcia s.l. Furthermore,
      this study offers valuable insights into the diversification of plant species in
      the highly impacted Atlantic forest of South America; evidence is presented that
      the lowest extinction rates are found inside refugia and that range expansion
      from unstable areas contributes to the highest levels of plant diversity in the
      Bahian refugium.

PMID- 25757472
TI  - The ubiquitin receptors DA1, DAR1, and DAR2 redundantly regulate
      endoreduplication by modulating the stability of TCP14/15 in Arabidopsis.
AB  - Organ growth involves the coordination of cell proliferation and cell growth with
      differentiation. Endoreduplication is correlated with the onset of cell
      differentiation and with cell and organ size, but little is known about the
      molecular mechanisms linking cell and organ growth with endoreduplication. We
      have previously demonstrated that the ubiquitin receptor DA1 influences organ
      growth by restricting cell proliferation. Here, we show that DA1 and its close
      family members DAR1 and DAR2 are redundantly required for endoreduplication
      during leaf development. DA1, DAR1, and DAR2 physically interact with the
      transcription factors TCP14 and TCP15, which repress endoreduplication by
      directly regulating the expression of cell-cycle genes. We also show that DA1,
      DAR1, and DAR2 modulate the stability of TCP14 and TCP15 proteins in Arabidopsis
      thaliana. Genetic analyses demonstrate that DA1, DAR1, and DAR2 function in a
      common pathway with TCP14/15 to regulate endoreduplication. Thus, our findings
      define an important genetic and molecular mechanism involving the ubiquitin
      receptors DA1, DAR1, and DAR2 and the transcription factors TCP14 and TCP15 that
      links endoreduplication with cell and organ growth. 

PMID- 25757473
TI  - Punctual transcriptional regulation by the rice circadian clock under fluctuating
      field conditions.
AB  - Plant circadian clocks that oscillate autonomously with a roughly 24-h period are
      entrained by fluctuating light and temperature and globally regulate downstream
      genes in the field. However, it remains unknown how punctual internal time
      produced by the circadian clock in the field is and how it is affected by
      environmental fluctuations due to weather or daylength. Using hundreds of samples
      of field-grown rice (Oryza sativa) leaves, we developed a statistical model for
      the expression of circadian clock-related genes integrating diurnally entrained
      circadian clock with phase setting by light, both responses to light and
      temperature gated by the circadian clock. We show that expression of individual
      genes was strongly affected by temperature. However, internal time estimated from
      expression of multiple genes, which may reflect transcriptional regulation of
      downstream genes, is punctual to 22 min and not affected by weather, daylength,
      or plant developmental age in the field. We also revealed perturbed progression
      of internal time under controlled environment or in a mutant of the circadian
      clock gene GIGANTEA. Thus, we demonstrated that the circadian clock is a
      regulatory network of multiple genes that retains accurate physical time of day
      by integrating the perturbations on individual genes under fluctuating
      environments in the field. 

PMID- 25757475
TI  - Is robotic mitral valve surgery more expensive than its conventional counterpart?
AB  - A best evidence topic in cardiac surgery was written according to a structured
      protocol. The question addressed was 'Is robotic mitral valve surgery more
      expensive than its conventional counterpart?' Altogether 19 papers were found
      using the reported search, of which 5 represented the best evidence to answer the
      clinical question. The authors, journal, date and country of publication, patient
      group studied, study type, relevant outcomes and results of these papers are
      tabulated. There is a general impression in the surgical community that robotic
      operations might incur prohibitive additional costs. There is a paucity of data
      in the literature regarding cost analysis in cardiac robotic surgery. From the
      five studies, four were single institution experiences and one was a database
      inquiry study. These four studies showed that operational costs are higher for
      robotic cases but this was partially (one study) or completely (three studies)
      offset by lower postoperative costs. Overall hospital costs were similar between
      the two approaches in three studies and one study showed higher costs in the
      robotic group. Higher operating theatre (OT) costs were driven mainly by use of
      robotic instruments (approximately US$1500 per case) and longer OT times. Savings
      in postoperative care were driven by shorter length of hospital stay (on average
      2 days fewer in robotic cases) and lower morbidity. If amortization cost, that
      is, the value of the initial capital investment on the robotic system divided by
      all operations performed, is included in this analysis, robotic approach becomes
      significantly more expensive by approximately US$3400 per case. The fifth study
      was a large national database inquiry in which robotic approach was found to be
      more expensive by US$600 per case excluding amortization cost and by US$3700 if
      amortization is included. We conclude that the total hospital cost of robotic
      mitral valve surgery is slightly higher than conventional sternotomy surgery. If
      amortization is taken into consideration, robotic cases are considerably more
      expensive. 

PMID- 25757474
TI  - Ontogeny of biochemical, morphological and functional parameters of
      synaptogenesis in primary cultures of rat hippocampal and cortical neurons.
AB  - BACKGROUND: Synaptogenesis is a critical neurodevelopmental process whereby pre-
      and postsynaptic neurons form apposed sites of contact specialized for chemical
      neurotransmission. Many neurodevelopmental disorders are thought to reflect
      altered patterns of synaptic connectivity, including imbalances between
      excitatory and inhibitory synapses. Developing rapid throughput approaches for
      assessing synaptogenesis will facilitate toxicologic and drug screening studies
      of neurodevelopmental disorders. The current study describes the use of high
      content imaging to quantify the ontogeny of excitatory and inhibitory synapses
      using in vitro models of neurodevelopment. These data are compared to biochemical
      and functional measures of synaptogenesis. RESULTS: The ontogenetic patterns of
      synapse formation were compared between primary rodent hippocampal and cortical
      neurons over 28 days in vitro (DIV). As determined by ELISA, the increase in
      synaptophysin expression levels as cultures matured was similar between
      hippocampal and cortical cultures. High-content imaging of immunoreactivity of
      excitatory and inhibitory synaptic biomarkers demonstrated an overall greater
      number of synapses in hippocampal relative to cortical neurons with marked
      differences in the pattern of inhibitory synapse development between these two
      neuronal cell types. Functional assays revealed that both the mean firing rates
      and mean bursting rates were significantly increased in cortical cultures
      relative to hippocampal cultures. This difference may reflect decreased
      inhibitory synaptic tone in cortical versus hippocampal cultures. CONCLUSIONS:
      These data demonstrate differences and similarities in the ontogeny of
      synaptogenesis between hippocampal and cortical neurons, depending on the
      biological level examined. Assessment of synaptophysin protein levels by ELISA
      showed a general increase in synapse formation in both cell types with increasing
      time in culture, while high-content imaging was able to delineate cell type
      dependent differences in formation of excitatory versus inhibitory synapses. The
      functional significance of differences in the balance of excitatory to inhibitory
      synapses was confirmed by the assessment of network activity using microelectrode
      arrays. These results suggest that high-content imaging and microelectrode arrays
      provide complementary approaches for quantitative assessment of synaptogenesis,
      which should provide a robust readout of toxicologic and pharmacologic effects on
      this critical neurodevelopmental event.

PMID- 25757476
TI  - Full sternotomy versus right anterior minithoracotomy for isolated aortic valve
      replacement in octogenarians: a propensity-matched study ?.
AB  - OBJECTIVES: Surgical aortic valve replacement (AVR) is increasingly performed in
      elderly patients with good perioperative outcomes and long-term survival,
      resulting in significant health-related quality-of-life benefits. This study
      aimed to evaluate the outcome of patients aged >= 80 years undergoing isolated
      AVR through a right anterior minithoracotomy (RAMT) and compare it with a full
      sternotomy (FS). METHODS: Two hundred and eighty-three elderly patients aged 80
      years or more underwent isolated AVR between February 2001 and September 2013.
      With propensity score matching (1 : 1), the outcomes of patients having minimally
      invasive surgery (RAMT) were compared with those in whom the FS approach had been
      employed (100 vs 100 patients). TAVRs and partial sternotomy cases were excluded
      from the analysis. RESULTS: There were two conversions in the RAMT group.
      Operative times did not significantly differ in the two groups. Patients in the
      RAMT group received a larger-sized prosthesis (P < 0.001) and were more likely to
      receive sutureless valves (P < 0.001). Shorter time for extubation (P < 0.001)
      and shorter hospital length of stay (P = 0.005) were observed in the RAMT group.
      Zero vs 4 (4.0%) (P = 0.043) patients had postoperative stroke and 2 (2.0%) vs
      zero (P = 0.16) had a transient ischaemic attack in the RAMT versus FS group,
      respectively. We registered the same rate of permanent pacemaker implant (P =
      0.47) and that of new-onset atrial fibrillation (P = 0.28) for both groups. Six
      patients died, with no significant difference for in-hospital mortality (P =
      0.68). No variable had a statistically significant predictive value for in
      hospital mortality. RAMT patients were more likely to be discharged home directly
      or via rehabilitation (P = 0.031). FS, along with four other factors,
      independently predicted longer hospital stay. Though the median follow-up
      duration was longer in the FS group (59 vs 24 months, P < 0.001), the two groups
      had similar survival rates at 5 years (80 vs 81%, P = 0.37). Ten factors were
      associated with long-term survival by Cox regression analysis, and RAMT had no
      statistical impact (P = 0.38). CONCLUSIONS: Minimally invasive AVR through right
      anterior minithoracotomy can be safely performed in patients aged >=80 years with
      acceptable morbidity and mortality rates. It is an expeditious and effective
      alternative to full sternotomy AVR and might be associated with lower
      postoperative stroke incidence, earlier extubation and shorter hospital stay.

PMID- 25757477
TI  - Results of surgical resection after induction chemoradiation for Pancoast tumours
      ?.
AB  - OBJECTIVES: Pancoast tumour is a rare neoplasia in which the optimal therapeutic
      management is still controversial. The traditional treatment of Pancoast tumour
      (surgery, radiotherapy or a combination of both) have led to an unsatisfactory
      outcome due to the high rate of incomplete resection and the lack of local and
      systemic control. The aim of the study was to determine the efficacy of the
      trimodality approach. METHODS: Fifty-six patients (male/female ratio: 47/9,
      median age: 64 years) in stage IIB to IIIB were treated during a period between
      1994 and 2013. Induction therapy consisted of 2-3 cycles of a platinum-based
      chemotherapy associated with radiotherapy (30-44 Gy). After restaging, eligible
      patients underwent surgery 2 to 4-week post-radiation. RESULTS: Thirty-two
      (57.1%) patients were cT3 and 24 (42.9%) cT4, 47 (83.9%) were N0 and 9 (16.1%)
      N+. Forty-eight (85.7%) patients underwent R0 resection and 10 (17.9%) had a
      complete pathological response (CPR). Thirty-day mortality rate was 5.4%, major
      surgical complications occurred in 6 (10.7%) patients. At the end of the follow
      up, 17 (30.4%) patients were alive and 39 (69.6%) died (29 for cancer-related
      causes), with an overall 5-year survival of 38%. At statistical analysis, stage
      IIB (P = 0.003), R0 resection (P = 0.03), T3 tumour (P = 0.002) and CPR (P =
      0.01) were significant independent predictors of better prognosis. CONCLUSIONS:
      This combined approach is feasible, and allows for a good rate of complete
      resection. Long-term survival rates are acceptable, especially for early stage
      tumours radically resected. Systemic control of disease still remains poor, with
      distant recurrence being the most common cause of death.

PMID- 25757479
TI  - Dynamics and stability of icosahedral Fe-Pt nanoparticles.
AB  - The structure, dynamics and stability of Fe-Pt nanoparticles have been
      investigated using DFT-based techniques: total energy calculations and molecular
      dynamics. The investigated systems included multi-shell and disordered
      nanoparticles of iron and platinum. The study concerns icosahedral particles with
      the magic number of atoms (55): iron-terminated Fe43Pt12, platinum-terminated
      Fe12Pt43, and disordered Fe27Pt28. Additionally, the Fe6Pt7 cluster has been
      investigated to probe the behaviour of extremely small Fe-Pt particles. Molecular
      dynamics simulations have been performed for a few temperatures between T = 150
      1000 K. The calculations revealed high structural instability of the Fe
      terminated nanoparticles and a strong stabilising effect of the Pt-termination in
      the shell-type icosahedral particles. The platinum termination prevented
      disordering of the particle even at T = 1000 K indicating very high melting
      temperatures of these Fe-Pt icosahedral structures. The analysis of evolution of
      the radial distribution function has shown a significant tendency of Pt atoms to
      move to the outside layer of the particles - even in the platinum deficient
      cases. 

PMID- 25757478
TI  - Socio-economic influences on anthropometric status in urban South African
      adolescents: sex differences in the Birth to Twenty Plus cohort.
AB  - OBJECTIVE: To investigate the associations of household and neighbourhood socio
      economic position (SEP) with indicators of both under- and overnutrition in
      adolescents and to explore sex differences. DESIGN: Analysis of anthropometric,
      household and neighbourhood SEP data from the Birth to Twenty Plus cohort born in
      1990. Anthropometric outcomes were BMI (thinness, overweight and obesity) and
      percentage body fat (%BF; low, high). Associations between these and the
      household wealth index, caregiver education and neighbourhood SEP tertile
      measures were examined using binary logistic regression. SETTING: Johannesburg
      Soweto, South Africa. SUBJECTS: Adolescents aged 17-19 years (n 2019; 48.2% men).
      RESULTS: Women had a significantly higher combined prevalence of
      overweight/obesity (26.2%) than men (8.2%) whereas men had a significantly higher
      prevalence of thinness than women (22.2% v. 10.6%, respectively). Having a low
      neighbourhood social support index was associated with higher odds of high %BF in
      women (OR=1.59; 95% CI 1.03, 2.44). A low household wealth index was associated
      with lower odds of both overweight (OR=0.31; 95% CI 0.12, 0.76) and high %BF in
      men (OR=0.28; 95% CI 0.10, 0.78). A low or middle household wealth index was
      associated with higher odds of being thin in men (OR=1.90; 95% CI 1.09, 3.31 and
      OR=1.80; 95% CI 1.03, 3.15, respectively). For women, a low household wealth
      index was associated with lower odds of being thin (OR=0.49; 95% CI 0.25, 0.96).
      CONCLUSIONS: The study highlights that even within a relatively small urban area
      the nutrition transition manifests itself differently in men and women and across
      SEP indicators. Understanding the challenges for different sexes at different
      ages is vital in helping to plan public health services.

PMID- 25757480
TI  - Mercuric chloride induced hepatotoxic and hematologic changes in rats: The
      protective effects of sodium selenite and vitamin E.
AB  - This study focuses on investigating the possible protective effect of sodium
      selenite (Na2SeO3) and/or vitamin E against mercuric chloride (HgCl2)-induced
      hepatotoxicity in rat. Male rats were given HgCl2 (1 mg/kg body weight (bw)) and
      HgCl2 plus Na2SeO3 (0.25 mg/kg bw) and/or vitamin E (100 mg/kg bw) daily via
      gavage for 4 weeks. HgCl2-treated groups had significantly higher white blood
      cell and thrombocyte counts than the control group. Serum activities of alkaline
      phosphatase, alanine aminotransferase, aspartate aminotransferase, gamma-glutamyl
      transferase, and lactate dehydrogenase significantly increased and serum levels
      of total protein, albumin, triglyceride, total cholesterol, and low-density
      lipoprotein cholesterol significantly decreased in the HgCl2-treated groups
      compared with control group. Malondialdehyde level significantly increased and
      superoxide dismutase, catalase, and glutathione peroxidase activities decreased
      in liver tissue of HgCl2-treated rats. Also, HgCl2 exposure resulted in
      histopathological changes. Supplementation of Na2SeO3 and/or vitamin E provided
      partial protection in hematological and biochemical parameters that were altered
      by HgCl2 As a result, Na2SeO3 and/or vitamin E significantly reduced HgCl2
      induced hepatotoxicity, but not protected completely. 

PMID- 25757481
TI  - Cytotoxic and genotoxic evaluation of different synthetic amorphous silica
      nanomaterials in the V79 cell line.
AB  - The nature of occupational risks and hazards in industries that produce or use
      synthetic amorphous silica (SAS) nanoparticles is still under discussion.
      Manufactured SAS occur in amorphous form and can be divided into two main types
      according to the production process, namely, pyrogenic silica (powder) and
      precipitated silica (powder, gel or colloid). The physical and chemical
      properties of SAS may vary in terms of particle size, surface area, agglomeration
      state or purity, and differences in their toxicity potential might therefore be
      expected. The aim of this study was to compare the cytotoxicity and genotoxicity
      of representative manufactured SAS samples in Chinese hamster lung fibroblasts
      (V79 cells). Five samples from industrial SAS producers were evaluated, that is,
      two pyrogenic SAS powders (with primary particle sizes of 20 nm and 25/70 nm),
      one precipitated SAS powder (20 nm) and two precipitated SAS colloids (15 and
      40/80 nm). V79 cell cultures were treated with different concentrations of SAS
      pre-dispersed in bovine serum albumin -water medium. Pyr (pyrogenic) 20, Pre
      (precipitated) 20 and Col (colloid) 15 significantly decreased the cell viability
      after 24 h of exposure, whilst Pyr 25/70 and Col 40/80 had negligible effects.
      The cytotoxicity of Pyr 20, Pre 20 and Col 15 was revealed by the induction of
      apoptosis, and Pyr 20 and Col 15 also produced DNA damage. However, none of the
      SAS samples generated intracellular reactive oxidative species, micronuclei or
      genomic mutations in V79 cells after 24 h of exposure. Overall, the results of
      this study show that pyrogenic, precipitated and colloidal manufactured SAS of
      around 20 nm primary particle size can produce significant cytotoxic and
      genotoxic effects in V79 cells. In contrast, the coarser-grained pyrogenic and
      colloid SAS (approximately 50 nm) yielded negligible toxicity, despite having
      been manufactured by same processes as their finer-grained equivalents. To
      explain these differences, the influence of particle agglomeration and oxidative
      species formation is discussed. 

PMID- 25757483
TI  - Towards single molecule switches.
AB  - The concept of using single molecules as key building blocks for logic gates,
      diodes and transistors to perform basic functions of digital electronic devices
      at the molecular scale has been explored over the past decades. However, in
      addition to mimicking the basic functions of current silicon devices, molecules
      often possess unique properties that have no parallel in conventional materials
      and promise new hybrid devices with novel functions that cannot be achieved with
      equivalent solid-state devices. The most appealing example is the molecular
      switch. Over the past decade, molecular switches on surfaces have been intensely
      investigated. A variety of external stimuli such as light, electric field,
      temperature, tunneling electrons and even chemical stimulus have been used to
      activate these molecular switches between bistable or even multiple states by
      manipulating molecular conformations, dipole orientations, spin states, charge
      states and even chemical bond formation. The switching event can occur either on
      surfaces or in break junctions. The aim of this review is to highlight recent
      advances in molecular switches triggered by various external stimuli, as
      investigated by low-temperature scanning tunneling microscopy (LT-STM) and the
      break junction technique. We begin by presenting the molecular switches triggered
      by various external stimuli that do not provide single molecule selectivity,
      referred to as non-selective switching. Special focus is then given to selective
      single molecule switching realized using the LT-STM tip on surfaces. Single
      molecule switches operated by different mechanisms are reviewed and discussed.
      Finally, molecular switches embedded in self-assembled monolayers (SAMs) and
      single molecule junctions are addressed. 

PMID- 25757482
TI  - Annexin A5 promotes macrophage activation and contributes to pulmonary fibrosis
      induced by silica particles.
AB  - OBJECTIVE: To investigate the contributions and underlying molecular mechanisms
      of annexin A5 toward silica-induced pulmonary fibrosis. METHODS: Male C57BL/6
      mice were randomly divided into three groups and instilled intratracheally with
      silica, saline, or air. Mice were euthanized at 3, 7, 14, or 28 days following
      treatment. Annexin A5 levels in serum and lung tissues were detected by enzyme
      linked immunosorbant assay (ELISA) assays or Western blots. The association of
      annexin A5 levels with silica-induced lung fibrosis was further investigated in
      the macrophage cell line, RAW264.7. Following exposure of these cells to silica
      at a concentration of 200 MUg/ml for 6 or 12 h, the expression levels of
      transforming growth factor beta1 (TGF-beta1), interleukin 1alpha (IL-1alpha), Fas
      ligand (FasL), and their downstream targets were evaluated by Western blots.
      Furthermore, annexin A5 and FasL were knocked down by small interfering
      ribonucleic acid (siRNA) and TGF-beta1 secretion into the cell culture medium was
      measured by ELISA assays or Western blots. RESULTS: Mice treated with silica
      demonstrated lung fibrosis at 28 days following exposure, whereas, in controls,
      only mild and transient inflammation was evident at day 3 and day 7
      postinstillation and was not present at day 14. Furthermore, silica-exposed mice
      exhibited significantly (p < 0.05) elevated levels of annexin A5 in serum and
      lung tissues, relative to control groups. Consistent with these findings, silica
      exposure of RAW264.7 cells for 6 or 12 h, led to an annexin A5-dependent increase
      in the expression levels of TGF-beta1, IL-1alpha, FasL, and their downstream
      target molecules. These silica-induced changes were reversed by siRNA-mediated
      knockdown of annexin A5, but downregulation of FasL led to increased annexin A5
      expression and reduced levels of TGF-beta1, IL-1alpha, and FasL downstream target
      molecules. CONCLUSIONS: These findings define a role of annexin A5 in promoting
      macrophage activation via Fas/FasL pathways in silica-induced lung fibrosis.

PMID- 25757484
TI  - Glutathione- and pH-responsive nonporous silica prodrug nanoparticles for
      controlled release and cancer therapy.
AB  - A myriad of drug delivery systems such as liposomes, micelles, polymers and
      inorganic nanoparticles (NPs) have been developed for cancer therapy. Very few of
      them, however, have the ability to integrate multiple functionalities such as
      specific delivery, high circulation stability, controllable release and good
      biocompatibility and biodegradability in a single system to improve the
      therapeutic efficacy. Herein, we report two types of stimuli-responsive nonporous
      silica prodrug NPs towards this goal for controlled release of anticancer drugs
      and efficient combinatorial cancer therapy. As a proof of concept, anticancer
      drugs camptothecin (CPT) and doxorubicin (DOX) were covalently encapsulated into
      silica matrices through glutathione (GSH)-responsive disulfide and pH-responsive
      hydrazone bonds, respectively, resulting in NPs with sizes tunable in the range
      of 50-200 nm. Both silica prodrug NPs showed stimuli-responsive controlled
      release upon exposure to a GSH-rich or acidic environment, resulting in improved
      anticancer efficacy. Notably, two prodrug NPs simultaneously taken up by HeLa
      cells showed a remarkable combinatorial efficacy compared to free drug pairs.
      These results suggest that the stimuli-responsive silica prodrug NPs are
      promising anticancer drug carriers for efficient cancer therapy. 

PMID- 25757485
TI  - The feasibility of an efficient drug design method with high-performance
      computers.
AB  - In this study, we propose a supercomputer-assisted drug design approach involving
      all-atom molecular dynamics (MD)-based binding free energy prediction after the
      traditional design/selection step. Because this prediction is more accurate than
      the empirical binding affinity scoring of the traditional approach, the compounds
      selected by the MD-based prediction should be better drug candidates. In this
      study, we discuss the applicability of the new approach using two examples.
      Although the MD-based binding free energy prediction has a huge computational
      cost, it is feasible with the latest 10 petaflop-scale computer. The
      supercomputer-assisted drug design approach also involves two important feedback
      procedures: The first feedback is generated from the MD-based binding free energy
      prediction step to the drug design step. While the experimental feedback usually
      provides binding affinities of tens of compounds at one time, the supercomputer
      allows us to simultaneously obtain the binding free energies of hundreds of
      compounds. Because the number of calculated binding free energies is sufficiently
      large, the compounds can be classified into different categories whose properties
      will aid in the design of the next generation of drug candidates. The second
      feedback, which occurs from the experiments to the MD simulations, is important
      to validate the simulation parameters. To demonstrate this, we compare the
      binding free energies calculated with various force fields to the experimental
      ones. The results indicate that the prediction will not be very successful, if we
      use an inaccurate force field. By improving/validating such simulation
      parameters, the next prediction can be made more accurate. 

PMID- 25757486
TI  - Preparation and evaluation of orally disintegrating tablets containing vitamin E
      as a model fat-soluble drug.
AB  - The purpose of the present study was to develop orally disintegrating tablets
      (ODTs) containing fat-soluble drugs that disintegrate rapidly while having
      appropriate tablet strength. We chose vitamin E (VE) as a model drug; d-alpha
      tocopheryl acetate, as the oily VE (VE-OI), and d-alpha-tocopheryl acid
      succinate, as the powder VE (VE-PO), were used. The oily VE was added directly to
      ODTs (VE-OI ODTs) and also used for the preparation of two types of VE granule,
      i.e., granules prepared using adsorption to calcium silicate (VE-FL granules) and
      granules prepared using spray-drying with gelatin (VE-SD granules); each type of
      granule was added to ODTs (VE-FL ODTs and VE-SD ODTs). Powder VE was added
      directly to ODTs (VE-PO ODTs). Various VE ODTs were prepared using these four
      additional methods with varying amounts of VE per tablet and were evaluated with
      respect to their manufacturability, physicochemical characteristics, and
      stability. It was demonstrated that a tablet porosity of 30% to 35% and tensile
      strength of 7 kg/cm(2) or greater are required to provide VE ODTs with rapid
      disintegration and appropriate tablet strength, and that VE-SD granules and
      powder VE are suitable forms of VE to be added. When stability tests of VE-SD
      ODTs and VE-PO ODTs were performed, VE-PO ODTs exhibited prolongation of
      disintegration time and increased tensile strength, whereas VE-SD ODTs showed
      none of these changes. These changes were thought to be attributable to a
      decrease in the pore size of VE-PO ODTs resulting from the softening and
      migration of powder VE under hot storage conditions.

PMID- 25757487
TI  - New approach to evaluate the lubrication process in various granule filling
      levels and rotating mixer sizes using a thermal effusivity sensor.
AB  - The principles of thermal effusivity are applied to an understanding of the
      detailed mechanisms of the lubrication process in a rotating mixer. The
      relationships and impact of the lubrication process by the pattern of powder
      flow, the filling level, and the rotating mixer size were investigated. Thermal
      effusivity profiles of the lubrication process, as obtained, indicate that
      lubrication is a two-phase process. The intersection point of the first and
      second phases (IPFS) is influenced by changing the filling level, thus changing
      the resulting number of avalanche flows created. The slope of the second phase
      (SSP) is influenced by the relationship between the number and the length of
      avalanche flows. Understanding this difference between the first and second
      phases is important to successfully evaluate the impact of proposed changes in
      the lubrication process. From this knowledge, a predictive model of the
      lubrication profile can be generated to allow an evaluation of proposed changes
      to the lubrication process. This model allows estimation of the lubrication
      profile at different filling levels and in different rotating mixer sizes. In
      this study, the actual lubrication profile almost coincides with the model
      predicted lubrication profile. Based on these findings, it is assumed that
      lubrication profiles at a commercial scale can be predicted from data generated
      at the laboratory scale. Further, it is assumed that changes in the filling level
      can also be estimated from the laboratory or current data. 

PMID- 25757488
TI  - Preparation and characterization of amphiphilic calixarene nanoparticles as
      delivery carriers for paclitaxel.
AB  - Two types of amphoteric calix[n]arene carboxylic acid (CnCA) derivative, i.e.,
      calix[6]arene hexa-carboxylic acid (C6HCA) and calix[8]arene octo-carboxylic acid
      (C8OCA), were synthesized by introducing acetoxyls into the hydroxyls of
      calix[n]arene (n=6, 8). C6HCA and C8OCA nanoparticles (NPs) were prepared
      successfully using the dialysis method. CnCA NPs had regular spherical shapes
      with an average diameter of 180-220 nm and possessed negative charges of greater
      than -30 mV. C6HCA and C8OCA NPs were stable in 4.5% bovine serum albumin
      solutions and buffers (pH 5-9), with a low critical aggregation concentration
      value of 5.7 mg.L(-1) and 4.0 mg.L(-1), respectively. C6HCA and C8OCA NPs
      exhibited good paclitaxel (PTX) loading capacity, with drug loading contents of
      7.5% and 8.3%, respectively. The overall in vitro release behavior of PTX from
      the CnCA NPs was sustained, and C8OCA NPs had a slower release rate compared with
      C6HCA NPs. These favorable properties of CnCA NPs make them promising
      nanocarriers for tumor-targeted drug delivery.

PMID- 25757489
TI  - Steroidal sapogenins and glycosides from the fibrous roots of Ophiopogon
      japonicus and Liriope spicata var. prolifera with anti-inflammatory activity.
AB  - Two new steroidal glycosides (1 and 2), together with 15 known compounds (3-17)
      were isolated from the fibrous roots of Ophiopogon japonicus, and three new
      steroidal glycosides (18-20), together with 14 known compounds (21-34) were
      isolated from the fibrous roots of Liriope spicata var. prolifera. The structures
      of the new compounds were elucidated on the basis of extensive one-dimensional
      (1D)- and 2D-NMR spectroscopic analyses and mass spectrometry. The isolated
      compounds were evaluated for their anti-inflammatory activity in vitro. Most of
      these steroidal glycosides showed significant inhibitory activity against
      neutrophil respiratory burst stimulated by phorbol myristate acetate. 

PMID- 25757490
TI  - Density of hydroxyl radicals generated in an aqueous solution by irradiating
      carbon-ion beam.
AB  - The density of hydroxyl radicals (.OH) produced in aqueous samples by exposure to
      X-ray or carbon-ion beams was investigated. The generation of .OH was detected by
      the electron paramagnetic resonance (EPR) spin-trapping technique using 5,5
      dimethyl-1-pyrroline-N-oxide (DMPO) as the spin-trapping agent. When the
      concentration of DMPO is in excess of the generated .OH, the production of DMPO
      OH (spin-trapped .OH) should be saturated. Reaction mixtures containing several
      concentrations (0.5-1685 mM) of DMPO were then irradiated by a 32 Gy 290 MeV
      carbon-ion beam (C290-beam) or X-ray. C290-beam irradiation was performed at the
      Heavy-Ion Medical Accelerator in Chiba (HIMAC, National Institute of Radiological
      Sciences, Chiba, Japan), applying different linear energy transfers (LET) (20-169
      keV/um). The amount of DMPO-OH in the irradiated samples was detected by EPR
      spectroscopy. The generation of DMPO-OH increased with the concentration of
      initial DMPO, displayed a shoulder around 3.3 mM DMPO, and reached a plateau.
      This plateau suggests that the generated .OH were completely trapped. Another
      linear increase in DMPO-OH measured in solutions with higher DMPO concentrations
      suggested very dense .OH generation (>1.7 M). Generation of .OH is expected to be
      localized on the track of the radiation beam, because the maximum concentration
      of measured DMPO-OH was 40 uM. These results suggested that both sparse (~3.3 mM)
      and dense (>1.7 M) .OH generation occurred in the irradiated samples. The
      percentage of dense .OH generation increased with increasing LET. Different types
      of dense .OH generation may be expected for X-ray and C290-beams.

PMID- 25757491
TI  - Preparation of chiral ligands connected with quaternary ammonium group for
      recyclable catalytic asymmetric transfer hydrogenation in ionic liquid.
AB  - Reuse of chiral ruthenium catalyst in catalytic asymmetric transfer hydrogenation
      (CATH) has attracted attention from economic and environmental viewpoints, and
      reactions using ionic liquids (ILs) as solvent are recognized as one of the most
      useful methods for reuse of the catalyst. We synthesized (1S,2S)-N-(p
      toluenesulfonyl)-1,2-diphenylethylenediamine (TsDPEN) derivatives with various
      ionic moieties, and investigated the effect of their structure with respect to
      catalytic ability and recyclability in CATH with ILs. Ligand 3a having an
      imidazolium group showed the best results, and significant differences were
      observed depending on the structure of the ionic moiety or the length of the
      alkyl chain connecting the ligand site and the ionic moiety. Among various
      prochiral ketones used as substrates at various cycles, 3a showed a relatively
      good result. 

PMID- 25757492
TI  - Microwave-assisted synthesis, molecular docking, and cholinesterase inhibitory
      activities of new ethanediamide and 2-butenediamide analogues.
AB  - A novel series of meta-substituted ethanediamide and 2-butenediamide derivatives
      were synthesized and tested for their ability to inhibit electric eel
      acetylcholinesterase (AChE) and equine serum butyrylcholinesterase (BuChE). The
      synthesized compounds were evaluated against ChE enzymes using the colorimetric
      method described by Ellman et al. (Biochem. Pharmacol., 7, 1961). It was revealed
      that some synthesized compounds exhibited high anticholinesterase activity, among
      which compounds 1f and 2f were the most active inhibitors against BuChE (IC50
      value=1.47 uM) and AChE (IC50 value=2.09 uM), respectively. Docking simulations
      revealed that the inhibitors 1f and 2f are capable of simultaneously binding the
      peripheral anionic site as well as the catalytic anionic site of both ChE
      enzymes. These derivatives are considered interesting candidates for Alzheimer's
      disease treatment.

PMID- 25757493
TI  - Effects of D-Leu residues on the helical secondary structures of L-Leu-based
      nonapeptides.
AB  - The influence of D-Leu residues on the helical structures of L-Leu-based
      nonapeptides was investigated. Specifically, the preferred conformations of four
      diastereomeric nonapeptides, Boc-(L-Leu-L-Leu-Aib)3-OMe (1); Boc-(L-Leu-L-Leu
      Aib)2-L-Leu-D-Leu-Aib-OMe (2), which contained one D-Leu residue; Boc-L-Leu-D-Leu
      Aib-L-Leu-L-Leu-Aib-L-Leu-D-Leu-Aib-OMe (3), which contained two D-Leu residues;
      and Boc-(L-Leu-D-Leu-Aib)3-OMe (4), were analyzed in solution and in the
      crystalline state. Peptide 1 formed a right-handed (P) 310-helix in solution.
      Peptides 2 and 3 both formed (P) 310-helices in solution and (P) alpha-helices in
      the crystalline state. Peptide 4 formed a (P) alpha-helix both in solution and in
      the crystalline state. 

PMID- 25757494
TI  - Antimicrobial and anti-biofilm activity of thiourea derivatives incorporating a 2
      aminothiazole scaffold.
AB  - A series of new thiourea derivatives of 1,3-thiazole have been synthesized. All
      obtained compounds were tested in vitro against a number of microorganisms,
      including Gram-positive cocci, Gram-negative rods and Candida albicans. Compounds
      were also tested for their in vitro tuberculostatic activity against the
      Mycobacterium tuberculosis H37Rv strain, as well as two 'wild' strains isolated
      from tuberculosis patients. Compounds 3 and 9 showed significant inhibition
      against Gram-positive cocci (standard strains and hospital strain). The range of
      MIC values is 2-32 ug/mL. Products 3 and 9 effectively inhibited the biofilm
      formation of both methicillin-resistant and standard strains of S. epidermidis.
      The halogen atom, especially at the 3rd position of the phenyl group, is
      significantly important for this antimicrobial activity. Moreover, all obtained
      compounds resulted in cytotoxicity and antiviral activity on a large set of DNA
      and RNA viruses, including Human Immunodeficiency Virus type 1 (HIV-1) and other
      several important human pathogens. Compound 4 showed activity against HIV-1 and
      Coxsackievirus type B5. Seven compounds resulted in cytotoxicity against MT-4
      cells (CC50<10 uM). 

PMID- 25757495
TI  - Tirucallane-type triterpenoids from the fruit of Ficus carica and their cytotoxic
      activity.
AB  - Nine new tirucallane-type triterpenoids, ficutirucins A-I (1-9), were isolated
      from the fruit of Ficus carica. Their structures were established on the basis of
      spectroscopic data and chemical methods. All isolates were evaluated for their
      cytotoxic activities against three human cancer cell lines, MCF-7, HepG-2, and
      U2OS. Compounds 1-3, 6, 7, and 9 exhibited moderate cytotoxic activities with
      IC50 values of 11.67-45.61 uM against one or more of the three cancer cell lines.

PMID- 25757496
TI  - Perioperative risk factors for surgical site infection in tibial tuberosity
      advancement: 224 stifles.
AB  - OBJECTIVE: To examine perioperative factors affecting surgical site infection
      (SSI) rate following tibial tuberosity advancement (TTA). STUDY DESIGN:
      Retrospective case series. SAMPLE POPULATION: 224 stifles in 186 dogs. METHODS:
      Medical records of dogs that underwent TTA in a single institution were reviewed.
      Information on signalment, anaesthetic and surgical parameters, as well as
      occurrence of SSI was recorded. Dogs were followed for a minimum of three months
      postoperatively. The association between perioperative factors and SSI was
      assessed using Chi-squared tests and binary logistic regression. RESULTS: The
      prevalence of SSI was 5.3% (12/224 TTA). Surgical time (p = 0.02) and anaesthesia
      time (p = 0.03) were significantly associated with SSI. For every minute increase
      in surgical time and anaesthesia time, the likelihood of developing SSI increased
      by seven percent and four percent respectively. The use of postoperative
      antimicrobial therapy was not significantly associated with lower SSI (p =
      0.719). Implants were removed in 1.3% of cases (3/224 TTA). CONCLUSIONS: The
      findings of this study suggest that increased surgical and anaesthesia times are
      significant risk factors for SSI in TTA, and that there is no evidence that
      postoperative prophylactic antimicrobial therapy is associated with SSI rate.

PMID- 25757497
TI  - Weaving a two-dimensional fishing net from titanoniobate nanosheets embedded with
      Fe3O4 nanocrystals for highly efficient capture and isotope labeling of
      phosphopeptides.
AB  - Qualitative and quantitative characterization of phosphopeptides by means of mass
      spectrometry (MS) is the main goal of MS-based phosphoproteomics, but suffers
      from their low abundance in the large haystack of various biological molecules.
      Herein, we introduce two-dimensional (2D) metal oxides to tackle this biological
      separation issue. A nanocomposite composed of titanoniobate nanosheets embedded
      with Fe3O4 nanocrystals (Fe3O4-TiNbNS) is constructed via a facile cation
      exchange approach, and adopted for the capture and isotope labeling of
      phosphopeptides. In this nanoarchitecture, the 2D titanoniobate nanosheets offer
      enlarged surface area and a spacious microenvironment for capturing
      phosphopeptides, while the Fe3O4 nanocrystals not only incorporate a magnetic
      response into the composite but, more importantly, also disrupt the restacking
      process between the titanoniobate nanosheets and thus preserve a greater specific
      surface for binding phosphopeptides. Owing to the extended active surface,
      abundant Lewis acid sites and excellent magnetic controllability, Fe3O4-TiNbNS
      demonstrates superior sensitivity, selectivity and capacity over homogeneous bulk
      metal oxides, layered oxides, and even restacked nanosheets in phosphopeptide
      enrichment, and further allows in situ isotope labeling to quantify aberrantly
      regulated phosphopeptides from sera of leukemia patients. This composite
      nanosheet greatly contributes to the MS analysis of phosphopeptides and gives
      inspiration in the pursuit of 2D structured materials for separation of other
      biological molecules of interests.

PMID- 25757498
TI  - Prison violence.

PMID- 25757499
TI  - Deciphering the specific high-affinity binding of cucurbit[7]uril to amino acids
      in water.
AB  - This work presents a systematic study on the host-guest interactions between the
      macrocyclic host molecule cucurbit[7]uril (CB[7]) and amino acids (AAs) including
      three basic AAs (Lys, Arg, and His) and three aromatic AAs (Phe, Tyr, and Trp) to
      elucidate the origin of the high selectivity of CB[7] toward AA residues in
      proteins. Complex formation between CB[7] and each AA was examined in solution
      (by isothermal titration calorimetry and NMR) as well as in the gas phase (by ion
      mobility mass spectrometry and collision-induced dissociation), and the results
      were further combined with computational investigations. Generally, the aromatic
      AAs show higher binding affinities than the basic AAs in buffer solutions with
      various pH values. On the contrary, the gas-phase stabilities of the basic AA
      complex ions are higher than those of the aromatic AA complex ions, suggesting
      that the direct ion-dipole interactions between the charged side chains of the
      basic AAs and the polar carbonyl groups of CB[7] predominate in the absence of
      water. The ion-dipole interactions are less significant in water, since the
      original interactions of the guests with water are lost upon complex formation.
      In contrast, the transfer of the hydrophobic groups from the bulk into the
      hydrophobic CB[7] cavity suffers less from the desolvation penalty, resulting in
      higher binding affinities in water. Therefore, initial guest solvation is another
      key factor which should be considered when designing high-affinity host-guest
      systems, in addition to the contribution from the release of high-energy water
      molecules from the CB[7] cavity (J. Am. Chem. Soc. 2012, 134, 15318-15323). 

PMID- 25757500
TI  - A Key Opinion Leader interview: insight into the research and career of Prof.
      Claudiu T Supuran.

PMID- 25757502
TI  - On: Jorge Schneider and colleagues 'Psychoanalytic training experience and
      postgraduate professional development'.

PMID- 25757501
TI  - Splicing defects caused by exonic mutations in PKD1 as a new mechanism of
      pathogenesis in autosomal dominant polycystic kidney disease.
AB  - The correct splicing of precursor-mRNA depends on the actual splice sites plus
      exonic and intronic regulatory elements recognized by the splicing machinery.
      Surprisingly, an increasing number of examples reveal that exonic mutations
      disrupt the binding of splicing factors to these sequences or generate new splice
      sites or regulatory elements, causing disease. This contradicts the general
      assumption that missense mutations disrupt protein function and that synonymous
      mutations are merely polymorphisms. Autosomal dominant polycystic kidney disease
      (ADPKD) is a common inherited disorder caused mainly by mutations in the PKD1
      gene. Recently, we analyzed a substantial number of PKD1 missense or synonymous
      mutations to further characterize their consequences on pre-mRNA splicing. Our
      results showed that one missense and 2 synonymous mutations induce significant
      defects in pre-mRNA splicing. Thus, it appears that aberrant splicing as a result
      of exonic mutations is a previously unrecognized cause of ADPKD. 

PMID- 25757503
TI  - Implementing novel trial methods to evaluate surgery for essential tremor.
AB  - INTRODUCTION: Deep brain stimulation (DBS) can provide dramatic essential tremor
      (ET) relief, however no Class I evidence exists. MATERIALS AND METHODS: Analysis
      methods: I) traditional cohort analysis; II) N-of-1 single patient randomised
      control trial and III) signal-to-noise (S/N) analysis. 20 DBS electrodes in ET
      patients were switched on and off for 3-min periods. Six pairs of on and off
      periods in each case, with the pair order determined randomly. Tremor severity
      was quantified with tremor evaluator and patient was blinded to stimulation.
      Patients also stated whether they perceived the stimulation to be on after each
      trial. RESULTS: I) Mean end-of-trial tremor severity 0.84 out of 10 on, 6.62 Off,
      t = - 13.218, p < 0.0005. II) N-of-1: 60% of cases had 12 correct perceptions (p
      = 0.001), 20% had 11 correct perceptions (p = 0.013). III) S/N: > 80% tremor
      reduction occurred in 99/114 'On' trials (87%), and 3/114 'Off' trials (3%). S/N
      ratio for 80% improvement with DBS versus spontaneous improvement was 487,757-to
      1. CONCLUSIONS: DBS treatment effect on ET is too large for bias to be a
      plausible explanation. Formal N-of-1 trial design, and S/N ratio method for
      presenting results, allows this to be demonstrated convincingly where
      conventional randomised controlled trials are not possible. CLASSIFICATION OF
      EVIDENCE: This study is the first to provide Class I evidence for the efficacy of
      DBS for ET.

PMID- 25757504
TI  - A comprehensive review of pesticides and the immune dysregulation: mechanisms,
      evidence and consequences.
AB  - Nowadays, in many communities, there is a growing concern about possible adverse
      effects of pesticides on human health. Reports indicate that during environmental
      or occupational exposure, pesticides can exert some intense adverse effects on
      human health through transient or permanent alteration of the immune system.
      There is evidence on the relation between pesticide-induced immune alteration and
      prevalence of diseases associated with alterations of the immune response. In the
      present study, direct immunotoxicity, endocrine disruption and antigenicity have
      been introduced as the main mechanisms working with pesticides-induced immune
      dysregulation. Moreover, the evidence on the relationship between pesticide
      exposure, dysregulation of the immune system and predisposition to different
      types of psychiatric disorders, cancers, allergies, autoimmune and infectious
      diseases are criticized. 

PMID- 25757506
TI  - Opposing roles of nitric oxide and rho-kinase in lipid metabolism in mice.
AB  - Dyslipidemia is a life-style disorder and is one of the important risk factors of
      cardiovascular diseases. Nitric oxide (NO) exerts beneficial effects on lipid
      metabolism through activation of hepatic sterol regulatory element-binding
      protein (SREBP)-2, a transcriptional factor for cholesterol metabolism and
      expression of LDL receptor, while Rho-kinase, an effecter protein of small G
      protein, RhoA, contributes to the pathogenesis of metabolic syndrome through
      suppressing the whole body energy consumption. However, the crosstalk between NO
      and Rho-kinase in regulation of lipid metabolism remains to be elucidated. In the
      present study, we used male wild-type (WT) mice and mice lacking three isoforms
      of NO synthase (NOSs(-/-)). WT mice were fed either normal diet (ND) or high-fat
      diet (HFD), while NOSs(-/-) mice were fed ND with or without a selective Rho
      kinase inhibitor, fasudil (100 mg/kg/day), for 6 weeks. At 6 weeks, plasma NOx
      concentration was significantly decreased and Rho-kinase activity and lipid
      levels were significantly elevated in HFD-fed WT mice and NOSs(-/-) mice compared
      with ND-fed WT mice. In the liver, SREBP-2 activity was reduced in NOSs(-/-)
      mice. Fasudil ameliorated lipid levels in HFD-fed WT mice and NOSs(-/-) mice
      without affecting SREBP-2 activity or LDL receptor expression, whereas it
      significantly enhanced phosphorylation of AMP-activated kinase (AMPK) in the
      liver and skeletal muscle. Importantly, the beneficial metabolic effects of
      fasudil were absent in HFD-fed AMPK(-/-) mice. These results provide the first
      evidence that NO and Rho-kinase play opposing roles for the lipid metabolism,
      suggesting that Rho-kinase inhibitors could be novel therapeutic agents of
      dyslipidemia. 

PMID- 25757505
TI  - MUC1/SEC and MUC1/Y overexpression is associated with inflammation in Sjogren's
      syndrome.
AB  - OBJECTIVES: To evaluate the expression and localization of MUC1/SEC and MUC1/Y
      isoforms in labial salivary glands (LSG) from Sjogren's syndrome patients (SS
      patients), as well as their in vitro expression induced by cytokines. SUBJECTS
      AND METHODS: Labial salivary gland from 27 primary SS patients and 22 non-SS
      sicca subjects were studied. Relative MUC1/SEC and MUC1/Y mRNA levels were
      determined by qPCR and protein levels by Western blotting. Induction of mucin
      mRNAs was assayed in vitro. Immunohistochemistry was used for localization.
      RESULTS: Relative MUC1/SEC and MUC1/Y mRNA and protein levels were significantly
      higher in LSG from SS patients. These mRNAs were induced by cytokines. MUC1/SEC
      and MUC1/Y were detected in acini apical region of control LSGs, and significant
      cytoplasmic accumulation was observed in acini of SS patients. MUC1/Y localized
      in acinar nuclei and cytoplasm of inflammatory cells of LSG from SS patients. A
      strong positive correlation was observed between cellular MUC1/SEC levels and
      glandular function determined by scintigraphy. CONCLUSIONS: We show for the first
      time that MUC1/SEC and MUC1/Y are expressed in LSG of both SS patients and non-SS
      sicca subjects. The observed overexpression and aberrant localization of MUC1/SEC
      and MUC1/Y and their induction by pro-inflammatory cytokines may favor the
      perpetuation of the inflammatory environment that disrupts the salivary glandular
      homeostasis in SS patients.

PMID- 25757507
TI  - Click conjugation of a binuclear terbium(III) complex for real-time detection of
      tyrosine phosphorylation.
AB  - Phosphorylation of proteins is closely associated with various diseases, and,
      therefore, its detection is vitally important in molecular biology and drug
      discovery. Previously, we developed a binuclear Tb(III) complex, which emits
      notable luminescence only in the presence of phosphotyrosine. In this study, we
      conjugated a newly synthesized binuclear Tb(III) complex to substrate peptides by
      using click chemistry. Using these conjugates, we were able to detect tyrosine
      phosphorylation in real time. These conjugates were superior to nonconjugated
      Tb(III) complexes for the detection of tyrosine phosphorylation, especially when
      the substrate peptides used were positively charged. Luminescence intensity upon
      phosphorylation was enhanced 10-fold, making the luminescence intensity of this
      system one of the largest among lanthanide luminescence-based systems. We also
      determined Michaelis-Menten parameters for the phosphorylation of various
      kinase/peptide combinations and quantitatively analyzed the effects of mutations
      in the peptide substrates. Furthermore, we successfully monitored the inhibition
      of enzymatic phosphorylation by inhibitors in real time. Advantageously, this
      system detects only the phosphorylation of tyrosine (phosphorylated serine and
      threonine are virtually silent) and is applicable to versatile peptide
      substrates. Our study thus demonstrates the applicability of this system for the
      analysis of kinase activity, which could lead to drug discovery. 

PMID- 25757509
TI  - Trans-fatty acids in cooking oils in Bogota, Colombia: changes in the food supply
      from 2008 to 2013.
AB  - OBJECTIVE: Long-chain n-3 fatty acid intake in Colombia is low because fish
      consumption is limited. Vegetable oils with high n-3 fatty acid content are
      recommended, but their concentrations of trans fats were high in previous
      studies. Thus, regular monitoring of the fatty acid composition of vegetable oils
      is required. Our objective was to quantify the fatty acid composition in
      commercially available oils in Bogota, Colombia and determine if composition
      changed from 2008 to 2013. DESIGN: Cross-sectional study. We obtained samples of
      all commercially available oils reported in a survey of low- and middle-income
      families with a child participating in the Bogota School Children Cohort.
      SETTING: Bogota, Colombia. SUBJECTS: Not applicable. RESULTS: Sunflower oil had
      the highest trans-fatty acid content (2.18%). Canola oil had the lowest
      proportion of trans-fatty acids (0.40%) and the highest n-3 fatty acid content
      (9.37%). In terms of percentage reduction from 2008 to 2013 in 18:1 and 18:2
      trans-fatty acids, canola oil had 89% and 65% reduction, mixed oils had 44% and
      48% reduction, and sunflower oil had 25% and 51 % reduction, respectively.
      Soyabean oil became widely available in 2013. CONCLUSIONS: The content of trans
      fatty acids decreased in all oils from 2008 to 2013, suggesting a voluntary
      reduction by industry. We believe that regular monitoring of the fatty acid
      composition of oils is warranted.

PMID- 25757508
TI  - Platelet mitochondrial dysfunction in critically ill patients: comparison between
      sepsis and cardiogenic shock.
AB  - INTRODUCTION: Platelet mitochondrial respiratory chain enzymes (that produce
      energy) are variably inhibited during human sepsis. Whether these changes occur
      even during other acute critical illness or are associated with impaired platelet
      aggregation and secretion (that consume energy) is not known. The aims of this
      study were firstly to compare platelet mitochondrial respiratory chain enzymes
      activity between patients with sepsis and those with cardiogenic shock, and
      secondly to study the relationship between platelet mitochondrial respiratory
      chain enzymes activity and platelet responsiveness to (exogenous) agonists in
      patients with sepsis. METHODS: This was a prospective, observational, case
      control study. Platelets were isolated from venous blood of 16 patients with
      severe sepsis or septic shock (free from antiplatelet drugs) and 16 others with
      cardiogenic shock, within 48 hours from admission to Intensive Care. Platelet
      mitochondrial respiratory chain enzymes activity was measured with
      spectrophotometry and expressed relative to citrate synthase activity, a marker
      of mitochondrial density. Platelet aggregation and secretion in response to
      adenosine di-phosphate (ADP), collagen, U46619 and thrombin receptor activating
      peptide were measured with lumiaggregometry only in patients with sepsis. In
      total, 16 healthy volunteers acted as controls for both spectrophotometry and
      lumiaggregometry. RESULTS: Platelets of patients with sepsis or cardiogenic shock
      similarly had lower mitochondrial nicotinamide adenine dinucleotide dehydrogenase
      (NADH) (P < 0.001), complex I (P = 0.006), complex I and III (P < 0.001) and
      complex IV (P < 0.001) activity than those of controls. Platelets of patients
      with sepsis were generally hypo-responsive to exogenous agonists, both in terms
      of maximal aggregation (P < 0.001) and secretion (P < 0.05). Lower mitochondrial
      NADH (R (2) 0.36; P < 0.001), complex I (R (2) 0.38; P < 0.001), complex I and
      III (R (2) 0.27; P = 0.002) and complex IV (R (2) 0.43; P < 0.001) activity was
      associated with lower first wave of aggregation with ADP. CONCLUSIONS: Several
      platelet mitochondrial respiratory chain enzymes are similarly inhibited during
      human sepsis and cardiogenic shock. In patients with sepsis, mitochondrial
      dysfunction is associated with general platelet hypo-responsiveness to exogenous
      agonists. TRIAL REGISTRATION: ClinicalTrials.gov NCT00541827 . Registered 8
      October 2007.

PMID- 25757510
TI  - Faecal incontinence in men referred for specialty care: a cross-sectional study.
AB  - AIM: Little is known about men with faecal incontinence. We compared clinical
      findings and quality of life in a large cohort of men and women with faecal
      incontinence to guide its evaluation and treatment in men. METHOD: We analysed
      men and women presenting to a tertiary referral centre with faecal incontinence
      between 2005 and 2013. Demographics, physical examination, anorectal physiology
      testing, symptom severity (Fecal Incontinence Severity Index) and quality of life
      (Fecal Incontinence Quality of Life Scale) were recorded. We determined
      differences between men and women and analysed the association between gender and
      quality of life. RESULTS: Data were obtained from 144 men and 897 women. Men with
      faecal incontinence were slightly younger than women (55.3 vs 57.6 years, P =
      0.001), more likely to report coexisting constipation (P = 0.004) and more likely
      to have normal internal and external sphincter function on physical examination
      (both P < 0.001). Anorectal physiology testing revealed fewer sphincter defects
      (P < 0.05) and less pudendal neuropathy (P < 0.05) in men compared with women.
      Although symptom severity and overall quality of life were similar, men had
      improved coping and less embarrassment compared with women after we adjusted for
      important clinical factors. CONCLUSION: Men with faecal incontinence presenting
      to a tertiary referral centre are more likely than women to have a mixed
      presentation characterized by constipation and less sphincter dysfunction. They
      exhibited better coping and less embarrassment than women. These findings should
      be taken into consideration when evaluating and treating men with faecal
      incontinence.

PMID- 25757511
TI  - Effect of sorbitol and glycerol on the stability of trypsin and difference
      between their stabilization effects in the various solvents.
AB  - The effect of glycerol and sorbitol on the stability of porcine pancreas trypsin
      was investigated in this work. Molecular dynamics simulation and thermostability
      results showed that trypsin has two flexible regions, and polyols (sorbitol and
      glycerol) stabilize the enzyme by decreasing the flexibility of these regions.
      Radial distribution function results exhibited that sorbitol and glycerol were
      excluded from the first water layer of the enzyme, therefore decrease the
      flexibility of the regions by preferential exclusion. Also, results showed that
      the stabilization effect of sorbitol is more than glycerol. This observation
      could be because of the larger decrease in the fluctuations of trypsin in the
      presence of sorbitol. We also examined the role of solvent's hydrophobicity in
      enzyme stabilization by sorbitol and glycerol. To do so, the thermostability of
      trypsin was evaluated in the presence of solvents with different hydrophobicity
      (methanol, ethanol, isopropanol and n-propanol) in addition to the polyols. Our
      results depicted that glycerol is a better stabilizer than sorbitol in the
      presence of hydrophobic solvents (n-propanol), whereas sorbitol is a better
      stabilizer than glycerol in the presence of hydrophilic solvents (methanol). 

PMID- 25757512
TI  - Gold nanoparticle-enabled blood test for early stage cancer detection and risk
      assessment.
AB  - When citrate ligands-capped gold nanoparticles are mixed with blood sera, a
      protein corona is formed on the nanoparticle surface due to the adsorption of
      various proteins in the blood to the nanoparticles. Using a two-step gold
      nanoparticle-enabled dynamic light scattering assay, we discovered that the
      amount of human immunoglobulin G (IgG) in the gold nanoparticle protein corona is
      increased in prostate cancer patients compared to noncancer controls. Two pilot
      studies conducted on blood serum samples collected at Florida Hospital and
      obtained from Prostate Cancer Biorespository Network (PCBN) revealed that the
      test has a 90-95% specificity and 50% sensitivity in detecting early stage
      prostate cancer, representing a significant improvement over the current PSA
      test. The increased amount of human IgG found in the protein corona is believed
      to be associated with the autoantibodies produced in cancer patients as part of
      the immunodefense against tumor. Proteomic analysis of the nanoparticle protein
      corona revealed molecular profile differences between cancer and noncancer serum
      samples. Autoantibodies and natural antibodies produced in cancer patients in
      response to tumorigenesis have been found and detected in the blood of many
      cancer types. The test may be applicable for early detection and risk assessment
      of a broad spectrum of cancer. This new blood test is simple, low cost, requires
      only a few drops of blood sample, and the results are obtained within minutes.
      The test is well suited for screening purpose. More extensive studies are being
      conducted to further evaluate and validate the clinical potential of the new
      test. 

PMID- 25757513
TI  - The VA Caregiver Support Line: A Gateway of Support for Caregivers of Veterans.
AB  - In passing the Caregivers and Veterans Omnibus Health Services Act of 2010,
      Congress created a legislative mandate for the Veterans Administration (VA) to
      strengthen its program of support services for caregivers of veterans. As part of
      this expansion, the VA implemented a nationwide toll-free telephone Caregiver
      Support Line (CSL). The CSL is a single point of entry system to link caregivers
      to national and local services to support care of a veteran. This article
      describes the CSL and its role in supporting aging veterans and their caregivers,
      discusses social workers' contributions to its development and implementation,
      and reports utilization data. 

PMID- 25757515
TI  - Sodium-ion diffusion mechanisms in the low cost high voltage cathode material
      Na(2+delta)Fe(2-delta/2)(SO4)3.
AB  - Bond-valence site energy modelling, classical molecular dynamics and DFT
      simulations were employed to clarify Na(+) ion migration in monoclinic
      Na2+deltaFe2-delta/2(SO4)3, the recently reported first representative of a new
      promising class of alluaudite-type high voltage cathode materials for sodium-ion
      batteries. Empirical potential parameters derived from our softBV bond valence
      parameter set reproduce experimental unit-cell parameters. Migration energy
      barrier calculations based on both these empirical and on ab initio approaches
      consistently show a strongly anisotropic and fairly fast Na(+) ion mobility along
      partially occupied Na(3) channels in the c-direction. Nominally fully occupied
      Na(1) sites are attached to these paths with a moderate activation energy as
      sources of mobile ions. At elevated temperatures separate parallel Na(2) channels
      contribute to the ionic conductivity. As such one-dimensional pathways are highly
      vulnerable to blocking by structural defects, the experimentally observed
      favourable rate performance can only be understood as a consequence of cross
      linking of the channels to a more robust higher-dimensional migration pathway
      network. Our static and dynamic bond valence pathway models for representative
      local structure models reveal that this cross-linking is achieved by the iron
      deficiency of the compound: iron vacancies act as low-lying interstitial sites
      that can be reached from both types of channels with moderate activation
      energies. Structural relaxations around the vacancies however reduce the sodium
      mobility along the channels. An analogous dual effect of blocking migration along
      the channels and promoting perpendicular migration would result from Na(+)/Fe(2+)
      antisite defects. Hence, further new alluaudite type transition metal sulphates
      can only be expected to yield a high rate performance, if their synthesis ensures
      the presence of a comparable transition metal sub-stoichiometry and/or a suitably
      tailored concentration of sodium/transition metal antisite defects. 

PMID- 25757514
TI  - Validation of sterility testing of cord blood: challenges and results.
AB  - BACKGROUND: Sterility testing for cord blood (CB) products is mandatory to
      prevent transplantation-transmitted microbial infections. Here, the automated
      BacT/ALERT (bioMerieux) culture system was validated to detect microbial
      contamination in CB units processed at the Canadian National Public Cord Blood
      Bank. STUDY DESIGN AND METHODS: A three-phase validation was developed. CB units
      were prepared with pentastarch (Phases 1 and 2) or hetastarch (Phase 3). In Phase
      1, CB was spiked with approximately 100 colony-forming units/mL of Pseudomonas
      aeruginosa, Klebsiella pneumoniae, Staphylococcus aureus, Staphylococcus
      epidermidis, Bacteroides fragilis, and Candida albicans. Plasma (8 mL) and buffy
      coat (BC; 0.5 and 8 mL) were inoculated into culture bottles. In Phases 2 and 3,
      a mix of red blood cells (RBCs) and plasma (4 mL each) was used as the inoculant.
      In Phase 3, Aspergillus brasiliensis was added as a test organism and microbial
      concentrations in the by-product RBCs and plasma were determined. The BC
      fractions were cryopreserved and tested 3 months later. RESULTS: In Phase 1,
      bacteria failed to grow in CB units containing antibiotics. Thus, antibiotic-free
      units were used for the other phases. C. albicans was not always captured in
      plasma, but using a mix of RBCs and plasma, all organisms were detected. The use
      of pentastarch or hetastarch did not affect microbial recovery. C. albicans and
      A. brasiliensis were preferentially recovered in RBCs and BC. Cryopreservation
      did not affect microbial survival during CB processing. CONCLUSIONS: A mix of
      plasma and RBCs is appropriate for CB sterility testing. Interestingly, fungi
      preferentially segregate to cellular fractions. The clinical significance of the
      bactericidal /or bacteriostatic effect of antibiotics in CB merits further
      investigation.

PMID- 25757518
TI  - "Aggregation induced phosphorescence" active "rollover" iridium(III) complex as a
      multi-stimuli-responsive luminescence material.
AB  - On reaction of 2,2'-bipyridine with iridium(iii), an "aggregation induced
      phosphorescence (AIP)" active "rollover" complex, [Ir(PPh3)2(bipy-H)(Cl)(H)]
      (bipy-H = kappa(2)-N,C-2,2'-bipyridine) or [Ir(bipy-H)], is obtained. The
      emission colour changes from bluish-green to yellowish-orange and vice versa
      after repeated protonation and deprotonation of [Ir(bipy-H)], respectively, which
      unequivocally supports its reversible nature. [Ir(bipy-H)] is sensitive to acids
      with different pKa values. Tuning of the emission properties can be achieved in
      the presence of acids with different pKas. This behaviour allows the complex,
      [Ir(bipy-H)], to function as a phosphorescent acid sensor in both solution and
      the solid state, as well as a chemosensor for detecting acidic and basic organic
      vapours. The protonated form, [Ir(bipy-H)H(+)], which is generated after
      protonation of [Ir(bipy-H)] can be used as a solvatochromic probe for oxygen
      containing solvents, and also shows vapochromic properties. The emission,
      absorption and (1)H NMR spectra of [Ir(bipy-H)] under acidic and basic conditions
      demonstrate its reversible nature. DFT based calculations suggest that changes in
      the electron affinity of the pyridinyl rings are responsible for all these
      processes. 

PMID- 25757517
TI  - Attentional bias in euthymic bipolar I disorder.
AB  - Little is known about the nature of the relation between information-processing
      biases and affective traits in bipolar disorder. The present study was designed
      to investigate whether attentional biases are evident in persons diagnosed with
      bipolar disorder when they are in a positive mood state, and whether biases are
      related to indices of emotion regulation and to prior history of mood episodes.
      Ninety adults diagnosed with bipolar I disorder and 81 controls with no lifetime
      mood disorder underwent a positive mood induction and then completed an emotion
      face dot-probe task; participants in the bipolar disorder group also completed a
      self-report measure of responses to positive affect. Attentional bias was not
      related to a diagnosis of bipolar disorder or to symptom severity. Consistent
      with hypotheses, analyses within the bipolar group indicated that greater
      dampening of positive affect related to significantly less attention paid to the
      positively valenced faces. Discussion focuses on the potential role of affective
      traits in shaping attentional bias in bipolar disorder. 

PMID- 25757519
TI  - Examining HIV, drug use and risk behaviours: A case study in the custodial
      settings of Thailand and Indonesia.
AB  - Custodial settings are high-risk environments for HIV. This paper examines
      publicly available data about the drug use and risk behaviours of Thai and
      Indonesian prisoners and outlines a process used to collect new data. In 2005,
      the Departments of Corrections in Thailand and Indonesia requested researchers
      examine HIV and drug use issues but the findings are too sensitive to publish.
      The Departments of Corrections in Thailand and Indonesia are using the results to
      develop public health responses. 

PMID- 25757516
TI  - Human settlement history between Sunda and Sahul: a focus on East Timor (Timor
      Leste) and the Pleistocenic mtDNA diversity.
AB  - BACKGROUND: Distinct, partly competing, "waves" have been proposed to explain
      human migration in(to) today's Island Southeast Asia and Australia based on
      genetic (and other) evidence. The paucity of high quality and high resolution
      data has impeded insights so far. In this study, one of the first in a forensic
      environment, we used the Ion Torrent Personal Genome Machine (PGM) for generating
      complete mitogenome sequences via stand-alone massively parallel sequencing and
      describe a standard data validation practice. RESULTS: In this first
      representative investigation on the mitochondrial DNA (mtDNA) variation of East
      Timor (Timor-Leste) population including >300 individuals, we put special
      emphasis on the reconstruction of the initial settlement, in particular on the
      previously poorly resolved haplogroup P1, an indigenous lineage of the Southwest
      Pacific region. Our results suggest a colonization of southern Sahul (Australia)
      >37 kya, limited subsequent exchange, and a parallel incubation of initial
      settlers in northern Sahul (New Guinea) followed by westward migrations <28 kya.
      CONCLUSIONS: The temporal proximity and possible coincidence of these latter
      dispersals, which encompassed autochthonous haplogroups, with the postulated
      "later" events of (South) East Asian origin pinpoints a highly dynamic migratory
      phase.

PMID- 25757520
TI  - First Dutch national guidelines--pharmacological care for detained opioid
      addicts.
AB  - Heterogenic care of addicted detainees in the various prisons in The Netherlands
      triggered the National Agency of Correctional Institutions of the Ministry of
      Justice, to order the Dutch Institute for Health Care Improvement (CBO) to
      formulate the first national guideline titled 'Pharmacological care for detained
      addicts'. This article presents the content of this guideline, which mainly
      focuses on opioid-dependent addicts. In The Netherlands, approximately 50% of the
      detainees are problematic substance abusers, while again half of this group
      suffers from psychiatric co-morbidity. In addition, somatic co-morbidity,
      especially infectious diseases, is also common. Due to the moderate outcome seen
      with voluntary drug counselling regimes in prison, there is a policy shift to
      extent utilization of legally enforced approaches. Continuity of care is of great
      importance. In case of opioid addicts this, in general, means continuation of
      methadone maintenance treatment. Aftercare immediately after detention and
      optimalization of medical information transfer is crucial. This guideline aims to
      realize optimal and uniform management of addiction disorders in the Dutch prison
      system.

PMID- 25757521
TI  - Sloshed and sentenced: A prevalence study of alcohol use disorders among
      offenders in the North East of England.
AB  - The annual cost of alcohol-related harm in the UK is estimated to be between
      L17.7 and L25.1 billion with healthcare costs alone reaching L2.7 billion and the
      costs of alcohol-fuelled crime and disorder accounting for L7.3 billion each
      year. The aim of the study was to examine the prevalence of alcohol use disorders
      (AUD) in prison and probation settings in the North East of England, and to
      compare the ability of the Alcohol Use Disorders Identification Test (AUDIT) and
      Offender Assessment System (OASys) at identifying alcohol-related need in
      probation clients. A quantitative prevalence study was carried out using
      anonymous questionnaires with participants from four prisons and three probation
      offices in the North East who voluntarily completed the AUDIT questionnaire
      during a 1-month period in 2006. Response outcomes on AUDIT were compared with
      OASys scores which identify alcohol-related need in probation. At the time of the
      study OASys scores were not available for offenders in prison. Seven hundred and
      fifteen questionnaires were completed. Sixty-three per cent of men and 57% of
      women were identified as having an AUD with over a third of all individuals
      scoring within the possibly dependant range (20+ on AUDIT). Around 40% of
      probation cases who were classified as either hazardous, harmful or possibly
      dependant drinkers on AUDIT were not identified by OASys. The results indicate
      that the prevalence of AUD in offenders is much higher than in the general
      population. In addition, current methods of identifying offenders with alcohol
      related need in probation are flawed and as many such people go undetected.
      Alcohol assessment procedures need to be improved in criminal justice setting
      order to correctly identify people with AUD. 

PMID- 25757522
TI  - 'Traumatisers or traumatised': Trauma experiences and personality characteristics
      of Australian prisoners.
AB  - BACKGROUND: Post-traumatic stress disorder (PTSD) is over represented in the
      prisoner population and is predictive of violence and suicide. This raises issues
      in relation to prisoner management, as well as theoretical issues such as why
      there is a range of vulnerability for PTSD. The current study examines the
      relationship between PTSD and personality profiles of prisoners. METHOD: Data
      from 1305 participants in the NSW survey of health in prisoners are examined to
      identify relationships between personality profiles derived from the Temperament
      and Character Inventory (TCI) and PTSD. Participants are grouped as experiencing
      no trauma; with a trauma history but no PTSD; and being diagnosed with PTSD. A
      logistic regression modelled significant predictors of PTSD. These data indicated
      that women prisoners report PTSD at twice the rate of males. An increased risk
      for PTSD is associated with high Harm Avoidance, low Self-Directedness, high
      Persistence and high Self-Transcendence. CONCLUSIONS: A combination of both
      temperament and character traits influences the trajectory towards PTSD
      development. Targeted treatment of these traits is needed in addressing the
      problems of prisoners with PTSD and managing the associated risks of violence and
      suicide.

PMID- 25757523
TI  - Fear of bullying among adult, young and juvenile prisoners: Its association with
      perpetration, victimisation and behavioural predictors.
AB  - The current study examines the association between fear of bullying and actual
      behaviour among male prisoners (n =234: 84 adult, 86 young and 66 juvenile). It
      explores if developmental models of aggression can assist with understanding fear
      and if there is evidence to support an application of the Applied Fear Response
      model. Participants completed the Direct and Indirect Prisoner Checklist-Scaled
      Revised and the Threat Appraisal Bullying measure. Fear of bullying did not
      differ across age. There were no significant relationships between fear and
      actual victimisation or perpetration for juveniles. Fear was a significant
      predictor of increased emotional and help-seeking behaviours in juveniles, and
      inhibited negative behaviours in adults. Fear of bullying was highest among young
      and juvenile 'bully-victims'. The need to account for fear of victimisation as
      opposed to focusing solely on victimisation experience is outlined, particularly
      in relation to younger prisoners (i.e. young adults and juvenile offenders). The
      value of developmental and environmental models in understanding aggression and
      victim reactions are discussed. 

PMID- 25757524
TI  - Enhanced chlamydia surveillance in New South Wales (Australia) prisons, 2005
      2007.
AB  - Chlamydia is currently the most frequently notified infectious disease in New
      South Wales (NSW). Published articles relating to chlamydia prevalence in
      Australian prison settings are sparse, but studies from the United Kingdom and
      the United States indicate relatively high chlamydia prevalence among young
      incarcerated individuals. This article reports on findings from an enhanced
      chlamydia surveillance programme in NSW prisons between 2005 and 2007. The
      authors report a relatively low chlamydia prevalence among the general population
      of NSW prisoners (compared with figures from the United Kingdom and United
      States), which by the end of 2007 was 4%. The average crude chlamydia
      notification rate for the NSW prison population during the review period was
      about four times that of the general NSW community - 716/100,000 during the
      review period compared with 175/100,000 in the NSW general community. The average
      crude chlamydia notification rate for Aboriginal prisoners during the review
      period was 1262/100,000, compared with 1470/100,000 in the general Australian
      Aboriginal population. The authors grapple with the dilemma of expanding
      chlamydia screening and treatment services for the sexual health benefits of
      prison populations with static prison health budgets on one hand, and limited
      evidence of cost-effectiveness of such an expensive intervention on the other. 

PMID- 25757525
TI  - The state of health care provision and extent of mental health in the prisons of
      the Arab world: A literature review and commentary.
AB  - Relevant literature was searched using MEDLINE, PsycINFO and Google in addition
      to Arabic search engines for information. Due to the shortage of scholarly
      articles on the subject, we broadened our search to publications from human
      rights organisation and articles in the mainstream press. We estimated the total
      carceral population in the member countries of the Arab league at 338,500
      prisoners, over 46,000 of whom could be suffering from severe mental illness. We
      relied on indirect indicators of mental health services such as the quality of
      medical care in general, accounts of prison conditions by prisoners and their
      families, and the abundant literature on human rights abuses. Despite a grim
      overall picture, we highlight signs of improvement in recent years. Psychiatrists
      working in Arabic prisons face a number of challenges.We comment on directions
      for the future in the field of correctional psychiatry in the Arab countries
      including from the perspective of research. 

PMID- 25757526
TI  - Monitoring harm reduction in European prisons via the Dublin Declaration.
AB  - The Dublin Declaration on Partnership to fight HIV/AIDS in Europe and Central
      Asia is the key policy document on HIV/AIDS in the European Region as a whole
      Among the Declaration's 33 actions for governments are many that apply to prison
      populations. Based upon an analysis of these commitments, and a review of the
      current status of states in meeting those targets, it is clear that the scale-up
      of HIV/AIDS prevention and treatment programmes and services in prisons lags far
      behind what is needed, what is available outside of prisons, and what is mandated
      within the Declaration itself. 

PMID- 25757528
TI  - Parent-Focused Prevention of Child Sexual Abuse.
AB  - Child sexual abuse (CSA) is a serious public health issue. Current after-the-fact
      approaches to treating victims and punishing offenders are not adequate to
      address a problem of this magnitude; development and rigorous evaluation of CSA
      prevention strategies are critical. We propose that CSA prevention efforts should
      target parents of young children. Parents have been neglected as a focus of CSA
      prevention; they merit attention given their potential to improve children's
      safety via effective communication and monitoring. This paper provides an
      overview of current strategies for reducing CSA prevalence and their limitations,
      presents a rationale for parent-focused CSA prevention, and discusses
      considerations pertinent to development of an effective parent-focused approach.
      Parent-focused CSA prevention offers potential as a public health approach to
      prevention of CSA, and it is time that we devote resources toward developing and
      studying this important area.

PMID- 25757527
TI  - 'Coming together to share, listen and learn': A conference with a vision.
AB  - The inaugural collaborative Canadian Prison-Academic-Community Health and
      Education was organized by the Collaborating Centre for Prison Health and
      Education and supported by the University of British Columbia (UBC), Nicola
      Valley Institute of Technology (NVIT) and Simon Fraser University (SFU) on 4th
      and 5th December 2008. The conference objective was to encourage and facilitate
      collaborative opportunities for enhancing health, education, research, service
      and advocacy, for the social well-being and (re)integration of individuals in
      custody, their families and communities. Four conference goals were articulated:
      (1) To share promising practices, current evidence and scholarship in health and
      education related to prison populations. (2) To bring together prison, academic
      and community members to create collaborative opportunities for partnerships and
      reciprocal learning. (3) To discuss and develop policy initiatives to promote
      positive change within prison health and education. (4) To explore the mental,
      physical, emotional and spiritual aspects of prisoner health and education. 

PMID- 25757529
TI  - Toxicity of Pb contaminated soils to the oribatid mite Platynothrus peltifer.
AB  - To understand the toxicity of Pb-polluted shooting fields, oribatid mites
      Platynothrus peltifer were exposed to shooting field soils containing 47-2398 mg
      Pb/kg dry weight (DW) and having pH(CaCl2) 3.2-6.8 and 3.8-13% organic matter
      (OM). Exposures also included artificial soils with different pH and OM contents
      as well as two natural soils used as controls. Exposures lasted for 2 (acute) and
      12 weeks (chronic). Survival, reproduction and uptake of Pb in the mites were
      related to total, water-extractable and 0.01 M CaCl2-extractable and porewater Pb
      concentrations as well as soil characteristics. After both the acute and chronic
      exposures, adult survival was not significantly affected, while upon chronic
      exposure reproduction was remarkably reduced in the acidic forest soils with Pb
      concentrations >=2153 mg/kg DW and pH(CaCl2) <= 3.5. P. peltifer juvenile numbers
      were significantly negatively and internal Pb concentrations in the mites were
      significantly positively related with total, extractable and porewater Pb
      concentrations. This study shows that P. peltifer is not very sensitive to Pb and
      therefore may not be a suitable indicator of Pb-polluted soils.

PMID- 25757530
TI  - Use of a risk nomogram to predict emergency department reattendance in older
      people after discharge: a validation study.
AB  - In older people, revisit to the emergency department (ED) in the short period
      after discharge is not entirely avoidable, but in a proportion of cases is
      preventable, and should ideally be minimised. We have previously derived a risk
      probability nomogram to predict the likelihood of revisit. In this study, we
      sought to validate the nomogram for use as a general risk stratification tool for
      use in older people being discharged from ED. We conducted a prospective cohort
      study, applying the nomogram to consecutive community dwelling discharged
      patients aged 65 and over. Patients were followed up at 28 days post-discharge to
      determine whether there had been any unplanned ED revisit in that period. We
      cross tabulated predicted risk versus revisit rates. In 1143 study subjects, we
      find the odds of revisit increases progressively with increasing strata of
      predicted risk, culminating in an OR of 9.7 (95% CI 4.7-19.9) in the highest risk
      group. The 28-day revisit rates across strata range from 16% through 65%, with
      the difference between strata being statistically highly significant (p < 0.001).
      The area under the ROC curve is 0.65. We conclude that the risk nomogram can
      classify older people discharged from ED into risk strata, and has modest overall
      predictive value.

PMID- 25757531
TI  - The literature supports policies promoting neonatal male circumcision in north
      america.

PMID- 25757532
TI  - Serum immunoglobulin G levels and peritonitis in peritoneal dialysis patients.
AB  - BACKGROUND: Peritonitis is a frequent and serious complication of peritoneal
      dialysis (PD). Whether low immunoglobulin level is associated with PD-related
      peritonitis is unknown. METHODS: We conducted a prospective study to assess
      whether immunoglobulin levels at PD onset could predict the occurrence of
      peritonitis. All patients starting peritoneal dialysis between 01/2005 and
      12/2010 at the University hospital of Besancon, France, were included in the
      study. RESULTS: Of 240 consecutive PD patients enrolled (mean follow-up 25 +/- 12
      months), 76 (32%) had at least one episode of peritonitis. Mean immunoglobulin
      (Ig)G level at PD start was lower in patients who subsequently experienced
      peritonitis (7.9 + 3.4 vs. 9.7 + 3.4 g/l, p = 0.005). An increased IgG level at
      PD onset was associated with a reduced risk of peritonitis [hazard ratio (HR)
      0.88, 95% confidence interval (CI) 0.80-0.97 for each increase of 1 g/l in IgG, p
      = 0.008]. IgG level <=6.4 g/l ("low IgG") was the best predictive value for the
      occurrence of subsequent peritonitis: 52 patients (24%) had low IgG levels. At
      multivariate analysis, both low IgG level (HR 2.49, 95% CI 1.32-4.69, p = 0.005)
      and diabetes (HR 2.78, 95% CI 1.49-5.20, p = 0.001) were predictive of the
      occurrence of peritonitis. CONCLUSION: Low IgG levels predict the occurrence of
      PD-related peritonitis. Randomized studies should determine whether such patients
      could benefit from intravenous immunoglobulin administration.

PMID- 25757533
TI  - One-stage lumbopelvic fixation in the treatment of lumbosacral junction
      tuberculosis.
AB  - PURPOSE: To investigate the clinical efficacy and feasibility of surgical
      treatment for lumbosacral junction tuberculosis by one-stage posterior
      debridement, interbody fusion, lumbopelvic fixation, and postural drainage.
      METHODS: A total of 15 cases with lumbosacral junction tuberculosis treated by
      one-stage posterior debridement, interbody fusion, lumbopelvic fixation, and
      postural drainage in our center from January 2005 to October 2011 were studied.
      Lumbosacral angle, visual analog scale (VAS), and neurological performance were
      assessed before and after surgery. RESULTS: All patients were followed for 28-56
      months post-operation (average, 40.7 +/- 7.7 months). No severe complications
      occurred. Bone fusion occurred in all patients at a mean of 8.4 months (range 6
      12 months) after surgery. The mean lumbosacral angle was significantly increased
      from the mean preoperative angle (20.9 degrees  +/- 1.8 degrees ) both post
      operatively (26.5 degrees  +/- 1.6 degrees ) and at final follow-up (25.3 degrees
      +/- 1.4 degrees ) (both P < 0.05). All patients had significant post-operative
      improvement in neurological performance and VAS scores. CONCLUSIONS: Our results
      suggest that one-stage posterior debridement, interbody fusion, lumbopelvic
      fixation, and postural drainage can be an effective and feasible treatment option
      for lumbosacral junction tuberculosis, offering fewer complications and a better
      quality of life.

PMID- 25757534
TI  - Non-instrumented extradural lumbar spine surgery under low-dose acetylsalicylic
      acid: a comparative risk analysis study.
AB  - PURPOSE: Coronary artery disease (CAD) affects over one-third of adults and is
      the leading cause of overall mortality and morbidity. Acetylsalicylic acid (ASA)
      is widely used in the prevention of CAD. As the population continues to mature,
      the number of patients presenting for spinal surgery that are under ASA treatment
      is rising. Studies investigating the outcome of lumbar spine surgeries without
      discontinuation of ASA therapy are lacking. The purpose of this study is to
      evaluate the peri- and postoperative bleeding and cardiovascular complication
      rates of patients undergoing non-instrumented, extradural, lumbar spine surgery
      with or without discontinuation of low-dose ASA. METHODS: We retrospectively
      compared the intra- and postoperative blood loss, morbidity, mortality, blood
      transfusion requirements and hematologic findings in the ASA group (40 patients)
      and the control group (62 patients). The diagnosis in all patients was either
      lumbar disc herniation or spinal canal stenosis. RESULTS: Intraoperative blood
      loss was 221 ml in the ASA group and 140.16 ml in the control group, showing no
      statistical difference (p = 0.08). Postoperative blood loss was 146.58 and 167.97
      ml in the ASA and control groups, respectively, also without statistical
      difference (p = 0.76). In the ASA group one patient developed a postoperative
      epidural hematoma needing revision surgery, while in the control group no
      postoperative epidural hematomas were seen (p = 0.40). In addition, blood
      transfusion requirements, hematologic findings, morbidity and mortality showed no
      significant difference. CONCLUSION: The continuation of ASA treatment in patients
      undergoing non-instrumented extradural lumbar spinal surgery seems to be safe and
      its perioperative continuation might therefore be recommended. Further studies
      confirming these results are needed.

PMID- 25757536
TI  - Graphene oxide immobilized enzymes show high thermal and solvent stability.
AB  - The thermal and solvent tolerance of enzymes is highly important for their
      industrial use. We show here that the enzyme lipase from Rhizopus oryzae exhibits
      exceptionally high thermal stability and high solvent tolerance and even
      increased activity in acetone when immobilized onto a graphene oxide (GO)
      nanosupport prepared by Staudenmaier and Brodie methods. We studied various forms
      of immobilization of the enzyme: by physical adsorption, covalent attachment, and
      additional crosslinking. The activity recovery was shown to be dependent on the
      support type, enzyme loading and immobilization procedure. Covalently immobilized
      lipase showed significantly better resistance to heat inactivation (the activity
      recovery was 65% at 70  degrees C) in comparison with the soluble counterpart
      (the activity recovery was 65% at 40  degrees C). Physically adsorbed lipase
      achieved over 100% of the initial activity in a series of organic solvents. These
      findings, showing enhanced thermal stability and solvent tolerance of graphene
      oxide immobilized enzyme, will have a profound impact on practical industrial
      scale uses of enzymes for the conversion of lipids into fuels. 

PMID- 25757535
TI  - Cardiac valve calcification is associated with presence and severity of coronary
      artery disease in patients with pre-dialysis chronic kidney disease.
AB  - BACKGROUND: Cardiac valve calcification is common in chronic kidney disease (CKD)
      patients. Coronary artery disease (CAD) is the one of major causes for increased
      cardiovascular mortality in CKD patients. We hypothesized that cardiac valve
      calcification is associated with the presence and the severity of CAD in pre
      dialysis CKD patients. METHODS: This study included 1166 patients who underwent
      transthoracic echocardiography for assessment of cardiac valve calcification and
      coronary angiography for assessment of CAD. The patients were divided into two
      groups according to estimated glomerular filtration rate (eGFR): pre-dialysis CKD
      group (n = 215, eGFR < 60 ml/min/1.73 m(2)) and non-CKD group (n = 951, eGFR >=
      60 ml/min/1.73 m(2)). RESULTS: In the pre-dialysis CKD group, subjects with
      aortic valve calcification (AVC), mitral valve calcification (MVC), and at least
      one valve calcification had more severe CAD compared with those without AVC, MVC,
      and any valve calcification. Multivariate analysis showed that pre-dialysis CKD
      patients who had AVC, MVC, and at least one valve calcification were 3.02 times
      (P = 0.033), 3.73 times (P = 0.029), and 3.31 times (P = 0.012) more likely to
      have CAD compared with those without AVC, MVC, and any valve calcification,
      respectively. However, in the non-CKD group, there was no association between
      cardiac valve calcification and the severity/presence of CAD. CONCLUSIONS:
      Cardiac valve calcification is associated with the presence and severity of CAD
      in pre-dialysis CKD. Assessment of cardiac valve calcification by means of
      transthoracic echocardiography could be a valuable non-invasive method for CAD
      risk stratification in pre-dialysis CKD patients.

PMID- 25757537
TI  - Conformational Change Near the Redox Center of Dihydrolipoamide Dehydrogenase
      Induced by NAD(+) to Regulate the Enzyme Activity.
AB  - Dihydrolipoamide dehydrogenase (LipDH) transfers two electrons from
      dihydrolipoamide (DHL) to NAD(+) mediated by FAD. Since this reaction is the
      final step of a series of catalytic reaction of pyruvate dehydrogenase multi
      enzyme complex (PDC), LipDH is a key enzyme to maintain the fluent metabolic
      flow. We reported here the conformational change near the redox center of LipDH
      induced by NAD(+) promoting the access of the DHL to FAD. The increase in the
      affinity of DHL to redox center was evidenced by the decrease in K M responding
      to the increase in the concentration of NAD(+) in Lineweaver-Burk plots. The
      fluorescence intensity of FAD transiently reduced by the addition of DHL was not
      recovered but rather reduced by the binding of NAD(+) with LipDH. The
      fluorescence decay lifetimes of FAD and Trp were prolonged in the presence of
      NAD(+) to show that FAD would be free from the electron transfer from the
      neighboring Tyrs and the resonance energy transfer efficiency between Trp and FAD
      lowered. These results consistently reveal that the conformation near the FAD and
      the surroundings would be so rearranged by NAD(+) to allow the easier access of
      DHL to the redox center of LipDH. 

PMID- 25757538
TI  - Tackling poison and leach: catalysis by dangling thiol-palladium functions within
      a porous metal-organic solid.
AB  - Self-standing thiol (-SH) groups within a Zr(IV)-based metal-organic framework
      (MOF) anchor Pd(II) atoms for catalytic applications: the spatial constraint
      prevents the thiol groups from sealing off/poisoning the Pd(II) center, while the
      strong Pd-S bond precludes Pd leaching, enabling multiple cycles of heterogeneous
      catalysis to be executed.

PMID- 25757540
TI  - The potential tyranny of statistical power.

PMID- 25757539
TI  - PI3K/AKT/mTOR pathway is activated after imatinib secondary resistance in
      gastrointestinal stromal tumors (GISTs).
AB  - Phosphatidylinositol-3-kinase (PI3K)/AKT/mammalian target of the rapamycin (mTOR)
      pathway activation may be related to imatinib resistance; however, no study has
      focused on whether signal conduction of this pathway will change after imatinib
      resistance. A total of 111 GIST samples from 91 patients were used in this study,
      including 20 pairs of samples before and after imatinib treatment.
      Immunohistochemistry was performed on tissue for p-KIT (phospho-KIT), PTEN
      (phosphatase and tensin homolog deleted on chromosome ten), PI3K, phospho-AKT (p
      AKT), phospho-4EBP1 (p-4EBP1) and phospho-S6 (p-S6RP). The activation of AKT/mTOR
      was significantly higher in imatinib secondary resistant GIST (53.1 %) than in
      imatinib-sensitive (27.1 %) and primary resistant GIST (33.3 %) (P = 0.049). In
      the analysis of 20 pairs of samples, comparing pre-imatinib GIST with on
      treatment ones, the PI3K status was changed from inactivated to activated in four
      cases each in eight patients with effective imatinib and 12 patients whose
      secondary resistance happened, respectively. AKT/mTOR status was inactivated in
      pre-imatinib and on-treatment samples in eight patients with effective imatinib;
      however, the status of six patients was changed from inactivated to activated in
      12 patients at the time of tumor progression. The negative expression of p-KIT
      was accompanied with PI3K pathway and/or AKT/mTOR pathway activity in some GISTs
      with secondary resistance. PI3K/AKT/mTOR pathway can be partly activated after
      imatinib secondary resistance in GIST. In this pathway, activation of AKT/mTOR is
      a more crucial factor, and PI3K activation may be the early part of secondary
      resistance. 

PMID- 25757541
TI  - Early lung function abnormalities in acromegaly.
AB  - BACKGROUND: Acromegaly is an insidious disorder caused by a pituitary growth
      hormone (GH)-secreting adenoma resulting in high circulating levels of GH and
      insulin-like growth factor I (IGF-I). Respiratory disorders are common
      complications in acromegaly, and can severely impact on quality of life,
      eventually affecting mortality. OBJECTIVES: The present study aimed to explore
      structural and functional lung alterations of acromegalic subjects. METHODS: We
      enrolled 10 consecutive patients (M/F: 5/5) affected by acromegaly. In all
      patients, magnetic resonance imaging (MRI) revealed the presence of pituitary
      tumor. All patients underwent clinical, lung functional, biological, and
      radiological assessments. Ten healthy age-matched subjects also served as
      controls. RESULTS: No statistically significant differences in lung function were
      detected between acromegalic and healthy subjects (p >= 0.05 for all analyses).
      However, the diffusing capacity for CO (TLCO) was significantly lower in the
      acromegalic group than in healthy subjects (TLCO% predicted: 78.1 +/- 16 vs. 90
      +/- 6 %, respectively, p = 0.04; KCO% predicted: 77 +/- 16 vs. 93 +/- 5 %, p =
      0.02, respectively). None of the lung function parameters correlated with
      duration of the disease, or with inflammatory marker of the airways. In
      acromegalics, biological (exhaled NO concentrations) and imaging (total lung
      volume, TLV, and mean lung density, MLD) evaluations were within normal values.
      The TLV measured by HRCT was 3540 +/- 1555 ml in acromegalics, and the MLD was 
      711 +/- 73 HU. None of the lung functional, radiological, and biological findings
      correlated with GH or IGF-I levels, and no correlation was found with duration of
      disease. CONCLUSIONS: In the current study, lung function evaluation allowed to
      detect early involvement of lung parenchyma, as assessed by TLCO and KCO, even in
      the absence of parenchymal density alterations of the lung by HRCT. These
      findings suggest to routinely include the carbon monoxide diffusing capacity in
      the lung function assessment for an early intervention in acromegaly.

PMID- 25757542
TI  - Multiple-trait genome-wide association study based on principal component
      analysis for residual covariance matrix.

PMID- 25757544
TI  - A single protocol for extraction of gDNA from bacteria and yeast.
AB  - Guanidine thiocyanate breakage of microorganisms has been the standard initial
      step in genomic DNA (gDNA) extraction of microbial DNA for two decades, despite
      the requirement for pretreatments to extract DNA from microorganisms other than
      Gram-negative bacteria. We report a quick and low-cost gDNA extraction protocol
      called EtNa that is efficient for bacteria and yeast over a broad range of
      concentrations. EtNa is based on a hot alkaline ethanol lysis. The solution can
      be immediately centrifuged to yield a crude gDNA extract suitable for PCR, or it
      can be directly applied to a silica column for purification. 

PMID- 25757545
TI  - Introduction of the hybcell-based compact sequencing technology and comparison to
      state-of-the-art methodologies for KRAS mutation detection.
AB  - The detection of KRAS mutations in codons 12 and 13 is critical for anti-EGFR
      therapy strategies; however, only those methodologies with high sensitivity,
      specificity, and accuracy as well as the best cost and turnaround balance are
      suitable for routine daily testing. Here we compared the performance of compact
      sequencing using the novel hybcell technology with 454 next-generation sequencing
      (454-NGS), Sanger sequencing, and pyrosequencing, using an evaluation panel of 35
      specimens. A total of 32 mutations and 10 wild-type cases were reported using 454
      NGS as the reference method. Specificity ranged from 100% for Sanger sequencing
      to 80% for pyrosequencing. Sanger sequencing and hybcell-based compact sequencing
      achieved a sensitivity of 96%, whereas pyrosequencing had a sensitivity of 88%.
      Accuracy was 97% for Sanger sequencing, 85% for pyrosequencing, and 94% for
      hybcell-based compact sequencing. Quantitative results were obtained for 454-NGS
      and hybcell-based compact sequencing data, resulting in a significant correlation
      (r = 0.914). Whereas pyrosequencing and Sanger sequencing were not able to detect
      multiple mutated cell clones within one tumor specimen, 454-NGS and the hybcell
      based compact sequencing detected multiple mutations in two specimens. Our
      comparison shows that the hybcell-based compact sequencing is a valuable
      alternative to state-of-the-art methodologies used for detection of clinically
      relevant point mutations. 

PMID- 25757546
TI  - Production of retroviral constructs for effective transfer and expression of T
      cell receptor genes using Golden Gate cloning.
AB  - Here we present an improved strategy for producing T-cell receptor (TCR)
      expressing retroviral vectors using a Golden Gate cloning strategy. This method
      takes advantage of the modular nature of TCR genes by directly amplifying TCR
      alpha and beta variable regions from RNA or cDNA, then cloning and fusing them
      with their respective constant region genes resident in a retroviral TCR
      expression vector. Our one-step approach greatly streamlines the TCR vector
      production process in comparison to the traditional three-step procedure that
      typically involves cloning whole TCR genes, producing a TCR expression cassette,
      and constructing a retroviral construct. To date, we have generated TCR vectors
      that transferred seven functional human/rhesus macaque TCRs into primary T cells.
      The approach also holds promise for the assembly of other genes with defined
      variable regions, such as immunoglobulins. 

PMID- 25757543
TI  - Affinity proteomics to study endogenous protein complexes: pointers, pitfalls,
      preferences and perspectives.
AB  - Dissecting and studying cellular systems requires the ability to specifically
      isolate distinct proteins along with the co-assembled constituents of their
      associated complexes. Affinity capture techniques leverage high affinity, high
      specificity reagents to target and capture proteins of interest along with
      specifically associated proteins from cell extracts. Affinity capture coupled to
      mass spectrometry (MS)-based proteomic analyses has enabled the isolation and
      characterization of a wide range of endogenous protein complexes. Here, we
      outline effective procedures for the affinity capture of protein complexes,
      highlighting best practices and common pitfalls. 

PMID- 25757547
TI  - SIFTER-T: a scalable and optimized framework for the SIFTER phylogenomic method
      of probabilistic protein domain annotation.
AB  - Statistical Inference of Function Through Evolutionary Relationships (SIFTER) is
      a powerful computational platform for probabilistic protein domain annotation.
      Nevertheless, SIFTER is not widely used, likely due to usability and scalability
      issues. Here we present SIFTER-T (SIFTER Throughput-optimized), a substantial
      improvement over SIFTER's original proof-of-principle implementation. SIFTER-T is
      optimized for better performance, allowing it to be used at the genome-wide
      scale. Compared to SIFTER 2.0, SIFTER-T achieved an 87-fold performance
      improvement using published test data sets for the known annotations recovering
      module and a 72.3% speed increase for the gene tree generation module in quad
      core machines, as well as a major decrease in memory usage during the realignment
      phase. Memory optimization allowed an expanded set of proteins to be handled by
      SIFTER's probabilistic method. The improvement in performance and automation that
      we achieved allowed us to build a web server to bring the power of Bayesian
      phylogenomic inference to the genomics community. SIFTER-T and its online
      interface are freely available under GNU license at
      http://labpib.fmrp.usp.br/methods/SIFTER-t/ and
      https://github.com/dcasbioinfo/SIFTER-t. 

PMID- 25757548
TI  - Stage IV breast cancer: a population-based study about prognostic factors
      according to HER2 and HR status.
AB  - We aim to describe trends in net survival (NS) and to assess the prognostic
      factors among women with de novo metastatic breast cancer (MBC) according to
      human epidermal growth factor receptor 2 (HER2) and hormone receptor (HR) status.
      Data on women suffering from de novo MBC and diagnosed from 1998 to 2009 were
      provided by the Cote-d'Or breast cancer registry. NS was described using the
      Pohar Perme estimator and prognostic factors were investigated in a generalised
      linear model. We identified 232 patients (mean age = 64.7). Median NS was 29.2
      months, 1- and 5-year NS were 76% and 26% respectively. The survival trend in
      patients with HER2-positive tumours who did not receive trastuzumab was similar
      to that in women with triple-negative tumours. A higher relative excess risk of
      death by cancer was observed for high-grade tumours [RER, relative excess rates =
      1.76 (95% CI, confidence intervals: 1.17-2.62) for Scarff Bloom Richardson grade
      3 vs. 1 + 2], while a lower risk was observed for luminal tumours [RER = 0.49
      (95% CI: 0.27-0.89)] and HER2-positive tumours treated with trastuzumab [RER =
      0.28 (95% CI: 0.14-0.59)], both compared with triple-negative tumours. Surgery of
      the primary tumour was associated with better survival [RER = 0.43 (95% CI: 0.28
      0.68)]. With half of the women dead before 29 months, stage IV breast cancer
      still has a bleak outlook. Progress should continue with new target therapies for
      both HR and HER2 receptors. 

PMID- 25757550
TI  - Dislocation-twin boundary interactions induced nanocrystalline via SPD processing
      in bulk metals.
AB  - This report investigated dislocation-twin boundary (TB) interactions that cause
      the TB to disappear and turn into a high-angle grain boundary (GB). The evolution
      of the microstructural characteristics of Hadfield steel was shown as a function
      of severe plastic deformation processing time. Sessile Frank partial dislocations
      and/or sessile unit dislocations were formed on the TB through possible
      dislocation reactions. These reactions induced atomic steps on the TB and led to
      the accumulation of gliding dislocations at the TB, which resulted in the
      transition from coherent TB to incoherent GB. The factors that affect these
      interactions were described, and a physical model was established to explain in
      detail the feasible dislocation reactions at the TB. 

PMID- 25757551
TI  - SMSaude: Design, Development, and Implementation of a Remote/Mobile Patient
      Management System to Improve Retention in Care for HIV/AIDS and Tuberculosis
      Patients.
AB  - BACKGROUND: The widespread and low cost of mobile phones and the convenience of
      short message service (SMS) text messaging suggest potential suitability for use
      with alternative strategies for supporting retention in care and adherence to the
      treatment of various chronic diseases, such as HIV and tuberculosis (TB). Despite
      the growing body of literature reporting positive outcomes of SMS text message
      based communication with patients, there is yet very little research about the
      integration of communication technologies and electronic medical records or
      electronic patient tracking systems. OBJECTIVE: To design, develop, and implement
      an integrated mobile phone text messaging system used to follow up with patients
      with HIV and TB in treatment in Mozambique. METHODS: Following the design science
      research methodology, we developed a Web-based system that provides support to
      patients. A case study involving three health care sites in Mozambique was a
      basis for discussing design issues for this kind of system. We used brainstorming
      techniques to solicit usability requirements, focus group meetings to discuss and
      define system architecture, and prototyping to test in real environments and to
      improve the system. RESULTS: We found six sets of system requirements that need
      to be addressed for success: data collection, telecommunication costs, privacy
      and data security, text message content, connectivity, and system scalability. A
      text messaging system was designed and implemented in three health facilities.
      These sites feed data into a central data repository, which can be used for
      analysis of operations and decision support. Based on the treatment schedule, the
      system automatically sent SMS text message appointment reminders, medication
      reminders, as well as motivational and educational messages to patients enrolled
      in antiretroviral therapy and TB treatment programs. CONCLUSIONS: We successfully
      defined the requirements for, designed, and implemented a mobile phone text
      messaging system to support HIV and TB treatments. Implementation of this system
      could improve patients' self-management skills and strengthen communication
      between patients and health care providers.

PMID- 25757553
TI  - [Safety in pediatric anesthesia: standards and checklists].

PMID- 25757552
TI  - Cafedrine/theodrenaline in anaesthesia: influencing factors in restoring arterial
      blood pressure.
AB  - BACKGROUND: Hypotensive states that require fast stabilisation of blood pressure
      can occur during anaesthesia. In 1963, the 20:1 mixture of
      cafedrine/theodrenaline (Akrinor) was introduced in Germany for use in
      anaesthesia and emergency medicine in the first-line management of hypotensive
      states. Though on the market for many years, few pharmacodynamic data are
      available on this combination net beta-mimetic agent. AIM: This study aimed to
      examine the drug combination in real-life clinical practice and recorded time to
      10 % mean arterial blood pressure (MAP) increase and heart rate. Furthermore,
      potential factors that influence drug effectiveness under anaesthesia were
      assessed. METHODS: Data were collected within a standardised anaesthesia
      protocol. A total of 353 consecutive patients (female/male = 149/204) who
      received cafedrine/theodrenaline after a drop in MAP >= 5% were included in the
      study. The time to 10 % increase in MAP, dosage of cafedrine/theodrenaline,
      volume loading, blood pressure and heart rate were monitored over time. RESULTS:
      Patients were a mean (standard deviation) of 64.4 +/- 15.1 years old with a
      baseline MAP of 82 +/- 14 mmHg, which dropped to a mean of 63 +/- 10 mmHg during
      anaesthesia without gender differences. Cafedrine/theodrenaline (1.27 +/- 1.0
      mg/kg; 64 +/- 50 ug/kg) significantly increased MAP (p < 0.001) by 11 +/- 16 mmHg
      within 5 min, reaching peak values within 17.4 +/- 9.0 min. Heart rate was not
      affected in a clinically significant manner. Cafedrine/theodrenaline induced a
      10% MAP increase after 7.2 +/- 4.6 min (women) and after 8.6 +/- 6.3 min (men) (p
      = 0.018). Independent of gender, the dose of cafedrine/theodrenaline required to
      achieve the observed MAP increase of 14 +/- 16 mmHg at 15 min was significantly
      different in patients with heart failure [1.78 +/- 1.67 mg/kg (cafedrine)/89.0 +/
      83.5 ug/kg (theodrenaline)] compared with healthy patients [1.16 +/- 0.77 mg/kg
      (cafedrine)/58.0 +/- 38.5 ug/kg (theodrenaline)] (p = 0.005). Concomitant
      medication with beta-blocking agents significantly prolonged the time to 10 % MAP
      increase [9.0 +/- 7.0 vs. 7.3 +/- 4.3 min (p = 0.008)]. CONCLUSION:
      Cafedrine/theodrenaline quickly restores MAP during anaesthesia. Female gender is
      associated with higher effectiveness, while heart failure and beta-blocker
      administration lower the anti-hypotonic effect. Prospective studies in defined
      patient populations are warranted to further characterise the effect of
      cafedrine/theodrenaline.

PMID- 25757554
TI  - [Stress and job satisfaction of future colleagues in anesthesiology].

PMID- 25757557
TI  - "Crystallographic" holes: new insights for a beneficial structural feature for
      photocatalytic applications.
AB  - One of the most fundamental aspects of the heterogeneous catalysis field is the
      manipulation of the catalysts' activity. In photocatalysis this is carried out by
      maximizing the right crystal plane of a semiconductor oxide. Until now, most of
      the papers have achieved this by a combination of different oxides, with noble
      metals and sometimes with carbon nanomaterials. In this work MWCNTs (multiwalled
      carbon nanotubes) were applied as "crystallization promoters" in a very simple,
      safe, one-step hydrothermal method. By this method TiO2 nano/micro crystals with
      exposed {001} facets were obtained in the first step. The next episode in the
      crystal manipulation "saga" was the modification of the (001) crystallographic
      plane's structure by creating ordered/own faceted "crystallographic holes". These
      elements are capable of further enhancing the obtained activity of titania
      microcrystals to a higher extent, as shown by the UV driven photocatalytic phenol
      degradation experiments. The appearance of the holes was "provoked" by simple
      calcination and their presence and influence were demonstrated by XPS and HRTEM.

PMID- 25757555
TI  - Organelles maintain spindle position in plant meiosis.
AB  - Accurate positioning of spindles is a critical aspect of cell division as it
      ensures that each daughter cell contains a single nucleus. In many flowering
      plants, two meiotic chromosome separations occur without intervening cytokinesis,
      resulting in two spindles in one cell during the second division. Here we report
      a detailed examination of two mutants, jason (jas) and parallel spindle1 (ps1),
      in which disturbed spindle position during male meiosis II results in the
      incorporation of previously separated chromosome groups into a single cell. Our
      study reveals that an organelle band provides a physical barrier between the two
      spindles. The loss of a single protein, JAS, from this organelle band leads to
      its disruption and a random movement of the spindles. JAS is largely associated
      with vesicles in the organelle band, revealing a role for vesicles in plant
      meiosis and that cytoplasmic events maintain spindle position during the
      chromosome division. 

PMID- 25757559
TI  - Neuropharmacology: Driving the urge to eat.

PMID- 25757558
TI  - Transcriptional regulation of microRNA-100, -146a, and -150 genes by p53 and
      NFkappaB p65/RelA in mouse striatal STHdh(Q7)/ Hdh(Q7) cells and human cervical
      carcinoma HeLa cells.
AB  - MicroRNA (miRNA) genes generally share many features common to those of protein
      coding genes. Various transcription factors (TFs) and co-regulators are also
      known to regulate miRNA genes. Here we identify novel p53 and NFkappaB p65/RelA
      responsive miRNAs and demonstrate that these 2 TFs bind to the regulatory
      sequences of miR-100, -146a and -150 in both mouse striatal and human cervical
      carcinoma cells and regulate their expression. p53 represses the miRNAs while
      NFkappaB p65/RelA induces them. Further, we provide evidence that exogenous p53
      inhibits NFkappaB p65/RelA activity by reducing its nuclear content and competing
      with it for CBP binding. This suggests for the existence of a functional cross
      talk between the 2 TFs in regulating miRNA expression. Moreover, promoter
      occupancy assay reveals that exogenous p53 excludes NFkappaB p65/RelA from its
      binding site in the upstream sequence of miR-100 gene thereby causing its
      repression. Thus, our work identifies novel p53 and NFkappaB p65/RelA responsive
      miRNAs in human and mouse and uncovers possible mechanisms of co-regulation of
      miR-100. It is to be mentioned here that cross-talks between p53 and NFkappaB
      p65/RelA have been observed to define the outcome of several biological processes
      and that the pro-apoptotic effect of p53 and the pro-survival functions of
      NFkappaB can be largely mediated via the biological roles of the miRNAs these TFs
      regulate. Our observation with cell lines thus provides an important platform
      upon which further work is to be done to establish the biological significance of
      such co-regulation of miRNAs by p53 and NFkappaB p65/RelA. 

PMID- 25757560
TI  - Disentangling calcium-driven astrocyte physiology.
AB  - Astrocytes seem to rely on relatively sluggish and spatially blurred Ca(2+) waves
      to communicate with fast and point-precise neural circuits. This apparent
      discrepancy could, however, reflect our current inability to understand the
      microscopic mechanisms involved. Difficulties in detecting and interpreting
      astrocyte Ca(2+) signals may have led to some prominent controversies in the
      field. Here, we argue that a deeper understanding of astrocyte physiology
      requires a qualitative leap in our experimental and analytical strategies. 

PMID- 25757561
TI  - Health related quality of life and care dependency among elderly hospital
      patients: an international comparison.
AB  - Many countries in Europe and the world have to cope with an aging population.
      Although health policy in many countries aims at increasing disability-free life
      expectancy, elderly patients represent a significant proportion of all patients
      admitted to different hospital departments. The aim of the research was to
      investigate the relationship between health-related quality of life (HRQOL) and
      the care dependency status among elderly hospital patients. In 2012, a
      descriptive survey was administered to a convenience sample of 325 elderly
      hospital patients (> 60 years) from The Netherlands (N = 125), from Poland (N =
      100), and from Turkey (N = 100). We employed the Functional Assessment of Chronic
      Illness Therapy (FACIT) Measurement System and the Care Dependency Scale. FACIT
      is a collection of HRQOL questionnaires that assess multidimensional health
      status in people with various chronic illnesses. From demographic variables,
      gender (female) (r = -0.13, p < 0.05), age and informal care given by family
      members (r = -0.27 to 0.27, p < 0.01) were significantly correlated with the care
      dependency status for the whole samples. All HRQOL variables, hearing aid and
      duration of illness correlated with care dependency status (r = -0.20 to 0.50, p
      < 0.01). Moreover, the FACIT sum score (Poland and Turkey) and functional
      wellbeing (The Netherlands) are significantly associated with the decrease in
      care dependency status. Thus, the FACIT variables are the most powerful
      indicators for care dependency. The study provides healthcare professionals
      insight into improvement of quality of care in all three countries. 

PMID- 25757562
TI  - Mid upper-arm circumference is an effective tool to identify infants and young
      children with severe acute malnutrition in India.
AB  - OBJECTIVE: To assess the appropriateness of current mid upper-arm circumference
      (MUAC) cut-offs to identify children with severe acute malnutrition in India.
      DESIGN: The analysis concerned 6307 children admitted to nutrition rehabilitation
      centres (2009-2011) where they received therapeutic care as per guidelines by WHO
      and the Indian Academy of Pediatrics. SETTING: States of Jharkhand, Madhya
      Pradesh and Uttar Pradesh, India. SUBJECTS: Children aged 6-59 months with
      bilateral pitting oedema or weight-for-height Z-score (WHZ)<-3 or MUAC<115 mm at
      admission. RESULTS: Children aged 6-23 months represented ~80 % of the
      admissions. Among them, the proportion with WHZ<-3 was similar to that with
      MUAC<115 mm (85.7 % v. 81.8 %); the proportion with MUAC<115 mm whose WHZ was <-3
      was 82.6 %; and the proportion with WHZ<-3 whose MUAC<115 mm was 78.8 %. MUAC<115
      mm was as effective as WHZ<-3 in identifying 6-59-month-old children with medical
      complications (32.2 % v. 31.6 %, respectively), the most important risk factor of
      death among oedema-free children. Furthermore, death rates in children with
      MUAC<115 mm were higher than in children with WHZ<-3 (0.61 % v. 0.58 %,
      respectively) and 91 % of the deaths among oedema-free children were deaths of
      children with MUAC<115 mm. CONCLUSIONS: In populations similar to those included
      in our analysis, MUAC<115 mm appears to be an appropriate criterion to identify
      children with severe acute malnutrition who are at a greater risk of medical
      complications and death, particularly among children 6-23 months old.

PMID- 25757563
TI  - Glutathione prevents preterm parturition and fetal death by targeting macrophage
      induced reactive oxygen species production in the myometrium.
AB  - Preterm birth is an inflammatory process resulting from the massive infiltration
      of innate immune cells and the production of proinflammatory cytokines in the
      myometrium. However, proinflammatory cytokines, which induce labor in vivo, fail
      to induce labor-associated features in human myometrial cells (MCs). We thus
      aimed to investigate if reactive oxygen species (ROS) production could be the
      missing step between immune cell activation and MC response. Indeed, we found
      that ROS production is increased in the human preterm laboring myometrium (27%
      ROS producing cells, respectively, versus 2% in nonlaboring controls), with 90%
      ROS production in macrophages. Using LPS-stimulated myometrial samples and cell
      coculture experiments, we demonstrated that ROS production is required for labor
      onset. Furthermore, we showed that ROS are required first in the NADPH oxidase
      (NADPHox)-2/NF-kappaB-dependent macrophage response to inflammatory stimuli but,
      more importantly, to trigger macrophage-induced MCs transactivation. Remarkably,
      in a murine model of LPS-induced preterm labor (inducing delivery within 17
      hours, with no pup survival), cotreatment with glutathione delayed labor onset up
      to 94 hours and prevented in utero fetal distress, allowing 46% pups to survive.
      These results suggest that targeting ROS production with the macrophage-permeable
      antioxidant glutathione could constitute a promising strategy to prevent preterm
      birth.

PMID- 25757564
TI  - Prostaglandin E2 transactivates the colony-stimulating factor-1 receptor and
      synergizes with colony-stimulating factor-1 in the induction of macrophage
      migration via the mitogen-activated protein kinase ERK1/2.
AB  - Prostaglandin E2 (PGE2), a key mediator of immunity, inflammation, and cancer,
      acts through 4 G-protein-coupled E-prostanoid receptors (EPs 1-4). Crosstalk
      between EPs and receptor tyrosine kinases also occurs. Colony-stimulating factor
      1 receptor (CSF-1R) is an RTK that sustains the survival, proliferation, and
      motility of monocytes/macrophages, which are an essential component of innate
      immunity and cancer development. The aim of this study was to investigate on a
      possible crosstalk between EP and CSF-1R. In BAC1.2F5 and RAW264.7 murine
      macrophages, CSF-1 (EC50 = 18.1 and 10.2 ng/ml, respectively) and PGE2 (EC50 =
      1.5 and 5.5 nM, respectively) promoted migration. PGE2 induced rapid CSF-1R
      phosphorylation that was dependent on Src family kinases (SFKs). CSF-1R
      inhibition reduced PGE2-elicited ERK1/2 phosphorylation and macrophage migration,
      indicating that CSF-1R plays a role in PGE2-mediated immunoregulation. EP4
      appeared responsible for functional PGE2/CSF-1R crosstalk. Furthermore, PGE2
      synergized with CSF-1 in inducing ERK1/2 phosphorylation and macrophage
      migration. ERK1/2 inhibition completely blocked migration induced by the
      combination CSF-1/PGE2. CSF-1/PGE2 functional interaction with respect to
      migration also occurred in bone marrow-derived murine macrophages (EC50 CSF-1,
      6.7 ng/ml; EC50 PGE2, 16.7 nM). These results indicated that PGE2 transactivates
      CSF-1R and synergizes with its signaling at ERK1/2 level in promoting macrophage
      migration.

PMID- 25757565
TI  - Amyloid beta peptide directly impairs pineal gland melatonin synthesis and
      melatonin receptor signaling through the ERK pathway.
AB  - Melatonin is the hormone produced by the pineal gland known to regulate
      physiologic rhythms and to display immunomodulatory and neuroprotective
      properties. It has been reported that Alzheimer disease patients show impaired
      melatonin production and altered expression of the 2 G protein-coupled melatonin
      receptors (MTRs), MT1 and MT2, but the underlying mechanisms are not known. Here
      we evaluated whether this dysfunction of the melatonergic system is directly
      caused by amyloid beta peptides (Abeta(1-40) and Abeta(1-42)). Abeta treatment of
      rat pineal glands elicited an inflammatory response within the gland, evidenced
      by the up-regulation of 52 inflammatory genes, and decreased the production of
      melatonin up to 75% compared to vehicle-treated glands. Blocking NF-kappaB
      activity prevented this effect. Exposure of HEK293 cells stably expressing
      recombinant MT1 or MT2 receptors to Abeta lead to a 40% reduction in
      [(125)I]iodomelatonin binding to MT1. ERK1/2 activation triggered by MTRs, but
      not by the beta2-adrenergic receptor, was markedly impaired by Abeta in HEK293
      transfected cells, as well as in primary rat endothelial cells expressing
      endogenous MTRs. Our data reveal the melatonergic system as a new target of
      Abeta, opening new perspectives to Alzheimer disease diagnosis and therapeutic
      intervention.

PMID- 25757566
TI  - A single-chain variable fragment intrabody prevents intracellular polymerization
      of Z alpha1-antitrypsin while allowing its antiproteinase activity.
AB  - Mutant Z alpha1-antitrypsin (E342K) accumulates as polymers within the
      endoplasmic reticulum (ER) of hepatocytes predisposing to liver disease, whereas
      low levels of circulating Z alpha1-antitrypsin lead to emphysema by loss of
      inhibition of neutrophil elastase. The ideal therapy should prevent polymer
      formation while preserving inhibitory activity. Here we used mAb technology to
      identify interactors with Z alpha1-antitrypsin that comply with both
      requirements. We report the generation of an mAb (4B12) that blocked alpha1
      antitrypsin polymerization in vitro at a 1:1 molar ratio, causing a small
      increase of the stoichiometry of inhibition for neutrophil elastase. A single
      chain variable fragment (scFv) intrabody was generated based on the sequence of
      mAb4B12. The expression of scFv4B12 within the ER (scFv4B12KDEL) and along the
      secretory pathway (scFv4B12) reduced the intracellular polymerization of Z alpha1
      antitrypsin by 60%. The scFv4B12 intrabody also increased the secretion of Z
      alpha1-antitrypsin that retained inhibitory activity against neutrophil elastase.
      MAb4B12 recognized a discontinuous epitope probably located in the region of
      helices A/C/G/H/I and seems to act by altering protein dynamics rather than
      binding preferentially to the native state. This novel approach could reveal new
      target sites for small-molecule intervention that may block the transition to
      aberrant polymers without compromising the inhibitory activity of Z alpha1
      antitrypsin.

PMID- 25757567
TI  - Removal of SOST or blocking its product sclerostin rescues defects in the
      periodontitis mouse model.
AB  - Understanding periodontal ligament (PDL) biology and developing an effective
      treatment for bone and PDL damage due to periodontitis have been long-standing
      aims in dental medicine. Here, we first demonstrated by cell lineage tracing and
      mineral double-labeling approaches that murine PDL progenitor cells display a 2-
      and 3-fold higher mineral deposition rate than the periosteum and endosteum at
      the age of 4 weeks, respectively. We next proved that the pathologic changes in
      osteocytes (Ocys; changes from a spindle shape to round shape with a >50%
      reduction in the dendrite number/length, and an increase in SOST) are the key
      pathologic factors responsible for bone and PDL damage in periostin-null mice (a
      periodontitis animal model) using a newly developed 3-dimensional FITC-Imaris
      technique. Importantly, we proved that deleting the Sost gene (a potent inhibitor
      of WNT signaling) or blocking sclerostin function by using the mAb in this
      periodontitis model significantly restores bone and PDL defects (n = 4-5; P <
      0.05). Together, identification of the key contribution of the PDL in normal
      alveolar bone formation, the pathologic changes of the Ocys in periodontitis bone
      loss, and the novel link between sclerostin and Wnt signaling in the PDL will aid
      future drug development in the treatment of patients with periodontitis.

PMID- 25757568
TI  - Multitarget fatty acid amide hydrolase/cyclooxygenase blockade suppresses
      intestinal inflammation and protects against nonsteroidal anti-inflammatory drug
      dependent gastrointestinal damage.
AB  - The ability of nonsteroidal anti-inflammatory drugs (NSAIDs) to inhibit
      cyclooxygenase (Cox)-1 and Cox-2 underlies the therapeutic efficacy of these
      drugs, as well as their propensity to damage the gastrointestinal (GI)
      epithelium. This toxic action greatly limits the use of NSAIDs in inflammatory
      bowel disease (IBD) and other chronic pathologies. Fatty acid amide hydrolase
      (FAAH) degrades the endocannabinoid anandamide, which attenuates inflammation and
      promotes GI healing. Here, we describe the first class of systemically active
      agents that simultaneously inhibit FAAH, Cox-1, and Cox-2 with high potency and
      selectivity. The class prototype 4: (ARN2508) is potent at inhibiting FAAH, Cox
      1, and Cox-2 (median inhibitory concentration: FAAH, 0.031 +/- 0.002 uM; Cox-1,
      0.012 +/- 0.002 uM; and Cox-2, 0.43 +/- 0.025 uM) but does not significantly
      interact with a panel of >100 off targets. After oral administration in mice,
      ARN2508 engages its intended targets and exerts profound therapeutic effects in
      models of intestinal inflammation. Unlike NSAIDs, ARN2508 causes no gastric
      damage and indeed protects the GI from NSAID-induced damage through a mechanism
      that requires FAAH inhibition. Multitarget FAAH/Cox blockade may provide a
      transformative approach to IBD and other pathologies in which FAAH and Cox are
      overactive.

PMID- 25757569
TI  - FE65 and FE65L1 amyloid precursor protein-binding protein compound null mice
      display adult-onset cataract and muscle weakness.
AB  - FE65 and FE65L1 are cytoplasmic adaptor proteins that bind a variety of proteins,
      including the amyloid precursor protein, and that mediate the assembly of
      multimolecular complexes. We previously reported that FE65/FE65L1 double knockout
      (DKO) mice display disorganized laminin in meningeal fibroblasts and a
      cobblestone lissencephaly-like phenotype in the developing cortex. Here, we
      examined whether loss of FE65 and FE65L1 causes ocular and muscular deficits, 2
      phenotypes that frequently accompany cobblestone lissencephaly. Eyes of
      FE65/FE65L1 DKO mice develop normally, but lens degeneration becomes apparent in
      young adult mice. Abnormal lens epithelial cell migration, widespread small
      vacuole formation, and increased laminin expression underneath lens capsules
      suggest impaired interaction between epithelial cells and capsular extracellular
      matrix in DKO lenses. Cortical cataracts develop in FE65L1 knockout (KO) mice
      aged 16 months or more but are absent in wild-type or FE65 KO mice. FE65 family
      KO mice show attenuated grip strength, and the nuclei of DKO muscle cells
      frequently locate in the middle of muscle fibers. These findings reveal that FE65
      and FE65L1 are essential for the maintenance of lens transparency, and their loss
      produce phenotypes in brain, eye, and muscle that are comparable to the clinical
      features of congenital muscular dystrophies in humans.

PMID- 25757570
TI  - Heritable IUGR and adult metabolic syndrome are reversible and associated with
      alterations in the metabolome following dietary supplementation of 1-carbon
      intermediates.
AB  - Metabolic syndrome (MetS), following intrauterine growth restriction (IUGR), is
      epigenetically heritable. Recently, we abrogated the F2 adult phenotype with
      essential nutrient supplementation (ENS) of intermediates along the 1-carbon
      pathway. With the use of the same grandparental uterine artery ligation model, we
      profiled the F2 serum metabolome at weaning [postnatal day (d)21; n = 76] and
      adulthood (d160; n = 12) to test if MetS is preceded by alterations in the
      metabolome. Indicative of developmentally programmed MetS, adult F2, formerly
      IUGR rats, were obese (621 vs. 461 g; P < 0.0001), dyslipidemic (133 vs. 67
      mg/dl; P < 0.001), and glucose intolerant (26 vs. 15 mg/kg/min; P < 0.01).
      Unbiased gas chromatography-mass spectrometry (GC-MS) profiling revealed 34 peaks
      corresponding to 12 nonredundant metabolites and 9 unknowns to be changing at
      weaning [false discovery rate (FDR) < 0.05]. Markers of later-in-life MetS
      included citric acid, glucosamine, myoinositol, and proline (P < 0.03).
      Hierarchical clustering revealed grouping by IUGR lineage and supplementation at
      d21 and d160. Weanlings grouped distinctly for ENS and IUGR by partial least
      squares discriminate analysis (PLS-DA; P < 0.01), whereas paternal and maternal
      IUGR (IUGR(pat)/IUGR(mat), respectively) control-fed rats, destined for MetS, had
      a distinct metabolome at weaning (randomForest analysis; class error < 0.1) and
      adulthood (PLS-DA; P < 0.05). In sum, we have found that alterations in the
      metabolome accompany heritable IUGR, precede adult-onset MetS, and are partially
      amenable to dietary intervention.

PMID- 25757573
TI  - Erratum to: Preoperative brain magnetic resonance imaging and postoperative
      delirium after off-pump coronary artery bypass grafting: a prospective cohort
      study.
AB  - Erratum to: Can J Anesth/J Can Anesth DOI 10.1007/s12630-015-0327-x. In the
      published version, the first name of the third author is incorrect and should
      read Naoaki Yamada as given in this erratum. The publisher apologizes most
      sincerely for this error.

PMID- 25757572
TI  - Localized attacks on spatially embedded networks with dependencies.
AB  - Many real world complex systems such as critical infrastructure networks are
      embedded in space and their components may depend on one another to function.
      They are also susceptible to geographically localized damage caused by malicious
      attacks or natural disasters. Here, we study a general model of spatially
      embedded networks with dependencies under localized attacks. We develop a
      theoretical and numerical approach to describe and predict the effects of
      localized attacks on spatially embedded systems with dependencies. Surprisingly,
      we find that a localized attack can cause substantially more damage than an
      equivalent random attack. Furthermore, we find that for a broad range of
      parameters, systems which appear stable are in fact metastable. Though robust to
      random failures-even of finite fraction-if subjected to a localized attack larger
      than a critical size which is independent of the system size (i.e., a zero
      fraction), a cascading failure emerges which leads to complete system collapse.
      Our results demonstrate the potential high risk of localized attacks on spatially
      embedded network systems with dependencies and may be useful for designing more
      resilient systems. 

PMID- 25757571
TI  - Interferon-alpha inducible protein 6 impairs EGFR activation by CD81 and inhibits
      hepatitis C virus infection.
AB  - Viral entry requires co-operative interactions of several host cell factors.
      Interferon (IFN) and the IFN-stimulated genes (ISGs) play a central role in
      antiviral responses against hepatitis C virus (HCV) infection. We examined the
      effect of interferon-alpha inducible protein 6 (IFI6) against HCV infection in
      human hepatoma cells. HCV RNA level or infectious foci were inhibited
      significantly by ectopic expression of IFI6. IFI6 impaired CD81 co-localization
      with claudin-1 (CLDN1) upon HCV infection or CD81 cross-linking by specific
      antibody. Activation of epidermal growth factor receptor (EGFR), a co-factor
      involved in CD81/CLDN1 interactions, was reduced in IFI6 expressing cells in
      response to HCV infection or CD81 cross linking by antibody, but not by treatment
      with EGF. Taken together, the results from our study support a model where IFI6
      inhibits HCV entry by impairing EGFR mediated CD81/CLDN1 interactions. This may
      be relevant to other virus entry processes employing EGFR. 

PMID- 25757576
TI  - Drivers of climate change impacts on bird communities.
AB  - Climate change is reported to have caused widespread changes to species'
      populations and ecological communities. Warming has been associated with
      population declines in long-distance migrants and habitat specialists, and
      increases in southerly distributed species. However, the specific climatic
      drivers behind these changes remain undescribed. We analysed annual fluctuations
      in the abundance of 59 breeding bird species in England over 45 years to test the
      effect of monthly temperature and precipitation means upon population trends.
      Strong positive correlations between population growth and both winter and
      breeding season temperature were identified for resident and short-distance
      migrants. Lagged correlations between population growth and summer temperature
      and precipitation identified for the first time a widespread negative impact of
      hot, dry summer weather. Resident populations appeared to increase following wet
      autumns. Populations of long-distance migrants were negatively affected by May
      temperature, consistent with a potential negative effect of phenological mismatch
      upon breeding success. There was evidence for some nonlinear relationships
      between monthly weather variables and population growth. Habitat specialists and
      cold-associated species showed consistently more negative effects of higher
      temperatures than habitat generalists and southerly distributed species
      associated with warm temperatures. Results suggest that previously reported
      changes in community composition represent the accumulated effects of spring and
      summer warming. Long-term population trends were more significantly correlated
      with species' sensitivity to temperature than precipitation, suggesting that
      warming has had a greater impact on population trends than changes in
      precipitation. Months where there had been the greatest warming were the most
      influential drivers of long-term change. There was also evidence that species
      with the greatest sensitivity to extremes of precipitation have tended to
      decline. Our results provide novel insights about the impact of climate change on
      bird communities. Significant lagged effects highlight the potential for altered
      species' interactions to drive observed climate change impacts, although some
      community changes may have been driven by more immediate responses to warming. In
      England, resident and short-distance migrant populations have increased in
      response to climate change, but potentially at the expense of long-distance
      migrants, habitat specialists and cold-associated species.

PMID- 25757574
TI  - Comparative Proteomics of Human and Macaque Milk Reveals Species-Specific
      Nutrition during Postnatal Development.
AB  - Milk has been well established as the optimal nutrition source for infants, yet
      there is still much to be understood about its molecular composition. Therefore,
      our objective was to develop and compare comprehensive milk proteomes for human
      and rhesus macaques to highlight differences in neonatal nutrition. We developed
      a milk proteomics technique that overcomes previous technical barriers including
      pervasive post-translational modifications and limited sample volume. We
      identified 1606 and 518 proteins in human and macaque milk, respectively. During
      analysis of detected protein orthologs, we identified 88 differentially abundant
      proteins. Of these, 93% exhibited increased abundance in human milk relative to
      macaque and include lactoferrin, polymeric immunoglobulin receptor, alpha-1
      antichymotrypsin, vitamin D-binding protein, and haptocorrin. Furthermore,
      proteins more abundant in human milk compared with macaque are associated with
      development of the gastrointestinal tract, the immune system, and the brain.
      Overall, our novel proteomics method reveals the first comprehensive macaque milk
      proteome and 524 newly identified human milk proteins. The differentially
      abundant proteins observed are consistent with the perspective that human
      infants, compared with nonhuman primates, are born at a slightly earlier stage of
      somatic development and require additional support through higher quantities of
      specific proteins to nurture human infant maturation. 

PMID- 25757575
TI  - Bilberry extract (Antho 50) selectively induces redox-sensitive caspase 3-related
      apoptosis in chronic lymphocytic leukemia cells by targeting the Bcl-2/Bad
      pathway.
AB  - Defect in apoptosis has been implicated as a major cause of resistance to
      chemotherapy observed in B cell chronic lymphocytic leukaemia (B CLL). This study
      evaluated the pro-apoptotic effect of an anthocyanin-rich dietary bilberry
      extract (Antho 50) on B CLL cells from 30 patients and on peripheral blood
      mononuclear cells (PBMCs) from healthy subjects, and determined the underlying
      mechanism. Antho 50 induced concentration- and time-dependent pro-apoptotic
      effects in B CLL cells but little or no effect in PBMCs. Among the main phenolic
      compounds of the bilberry extract, delphinidin-3-O-glucoside and delphinidin-3-O
      rutinoside induced a pro-apoptotic effect. Antho 50-induced apoptosis is
      associated with activation of caspase 3, down-regulation of UHRF1, a rapid
      dephosphorylation of Akt and Bad, and down-regulation of Bcl-2. Antho 50
      significantly induced PEG-catalase-sensitive formation of reactive oxygen species
      in B CLL cells. PEG-catalase prevented the Antho 50-induced induction of
      apoptosis and related signaling. The present findings indicate that Antho 50
      exhibits strong pro-apoptotic activity through redox-sensitive caspase 3
      activation-related mechanism in B CLL cells involving dysregulation of the
      Bad/Bcl-2 pathway. This activity of Antho 50 involves the glucoside and
      rutinoside derivatives of delphinidin. They further suggest that Antho 50 has
      chemotherapeutic potential by targeting selectively B CLL cells. 

PMID- 25757578
TI  - The cracks are showing: private healthcare providers.

PMID- 25757577
TI  - Orexin A-mediated AKT signaling in the dentate gyrus contributes to the
      acquisition, expression and reinstatement of morphine-induced conditioned place
      preference.
AB  - Accumulating evidence indicates that the hippocampal dentate gyrus (DG), a
      critical brain region contributing to learning and memory, is involved in the
      addiction and relapse to abused drugs. Emerging studies also suggest the role of
      orexin signaling in the rewarding behavior induced by repeated exposure to
      opiates. In the present study, we investigated the dynamic adaptation of orexin
      signaling in the DG and its functional significance in the acquisition,
      expression, maintenance of and relapse to rewarding behavior induced by morphine.
      Repeated place conditioning with morphine significantly increased the orexin A
      content released from the lateral hypothalamic area projecting neurons into the
      DG. Local infusions of orexin A into the DG sensitized the acquisition of and
      relapse to the conditioned place preference induced by morphine. The application
      of the orexin receptor type 1 (OXR1) antagonist SB334867 significantly abolished
      the acquisition, expression and maintenance of the conditioned place preference
      induced by repeated exposure to morphine. Furthermore, the significant increase
      of the phosphorylation of AKT in the DG was associated with preference for the
      morphine-paired chamber in rats, which was reversed by the local administration
      of an OXR1 antagonist. Thus, these findings suggested that the dynamic
      upregulation of orexin A signaling, via the AKT pathway in the DG, may promote
      the acquisition and maintenance of opioid-induced craving behaviors and may
      increase sensitivity to the rewarding effect of subsequent opioids. 

PMID- 25757579
TI  - Plain packs and more: towards a smoke-free future.

PMID- 25757580
TI  - Management of common neonatal problems.
AB  - The important causes of neonatal mortality are congenital malformations, birth
      trauma, neonatal infections, and respiratory, metabolic and heart diseases.
      Although many of the neonatal problems are benign, self-limited and treatable,
      some are life-threatening and a direct cause of disability and death.
      Professionals who provide care for children must be aware of these problems,
      their natural history, their impact on children's heath and their treatment.
      Birth marks are common and often harmless, but parents need explanation and
      reassurance. Follow-up appointments are often necessary to ensure the general
      wellbeing of the affected children. Birth trauma, such as intracranial
      haemorrhage or arm paralysis, may occur during delivery, and treatment at a
      specialised unit is usually required. The prognosis of neonatal infections is
      generally poor, with high mortality unless treatment is started promptly and
      adequately. Respiratory diseases occur mainly in low birth-weight infants who may
      require mechanical ventilation. Metabolic and heart diseases are rare, but early
      detection is essential to ensure a high survival rate. 

PMID- 25757581
TI  - Living with faecal incontinence: a 10-year follow-up study.
AB  - Faecal incontinence (FI) is a taboo subject, and people living with it can feel
      stigmatised. This article reports on a 10-year qualitative follow-up to an
      initial constructivist-grounded theory project, investigating living with FI.
      This article will also look back at the initial study and the 5-year follow-up
      study undertaken. The research examines the challenges associated with living
      with FI and different ways of managing the condition, including the importance of
      social support. 

PMID- 25757582
TI  - 'It's the hearing that is last to go': a case of traumatic head injury.
AB  - This article explores the literature related to acquired brain injury (ABI) and
      is followed by a case study of one patient with ABI, which reflects how the
      evidence, when implemented by a team of health professionals, can have a positive
      impact on recovery. Gregor is a middle-aged Polish man who suffered traumatic ABI
      when knocked down by a car. He spent a number of years in a specialist
      neurosurgical unit, then a rehabilitation unit, and for the past several years
      has been cared for in a care home. For most of this time he was in a coma. He
      began to come out of his coma and during his time in the care home received
      intensive physiotherapy and speech therapy. At the time of his brain injury
      Gregor could speak no English yet years later, when he began to regain
      consciousness, he was able to speak and understand English, a fact that might be
      attributed in part to 6 years of nurses talking to him in English as part of
      caring for him. Nurses are always told that hearing is the last of the senses to
      be lost when a person is unconscious or has a brain injury (Sisson, 1990). The
      case study presented in this article demonstrates the potential power of talking
      to a patient when providing care, even when that patient is in a coma, and the
      impact this may have had on Gregor. It also demonstrates the importance of the
      need for evidence-based neuro-rehabilitation, including multi-professional
      working by a team of specialist physiotherapists, nurses, speech therapists,
      continence specialist nurse and nutritionist.

PMID- 25757583
TI  - Exploring failure to fail in pre-registration nursing.
AB  - Failing a student nurse can be a challenging task for mentors in the learning
      environment. It is often an unpleasant experience for all involved. However,
      mentors have a duty to uphold the reputation of the nursing profession and be the
      gatekeepers of the profession and the Nursing and Midwifery Council (NMC)
      professional register. Failing a student who is not meeting the required
      competence in the learning environment is a way of safeguarding the nursing
      profession and the future workforce. This article will look at the mentor's role
      when a student nurse is identified as not meeting competencies in the learning
      environment. The article explores the importance of following process when
      identifying weak students and the role that clinical educators and university
      staff have in supporting mentors when a student is deemed to be failing their
      learning experience. 

PMID- 25757584
TI  - Selecting and fitting a penile sheath.

PMID- 25757585
TI  - Relationships: from staff nurse to nurse consultant.

PMID- 25757586
TI  - Does UK nursing research have an impact on care delivery?
AB  - Professor Dame Jessica Corner, Chair of the Council of Deans of Health, and
      Professor Alan Glasper of the University of Southampton discuss the impact
      potential of the Research Excellence Framework results, and how world-leading
      nursing research is transforming care delivery. 

PMID- 25757587
TI  - Parliament gets tough on NHS complaints.
AB  - John Tingle discusses the House of Commons Select Committee on Health report on
      NHS complaints and raising concerns. 

PMID- 25757588
TI  - Commissioning: CQUINs.

PMID- 25757589
TI  - Preventing discrimination through role modelling.

PMID- 25757590
TI  - Rising to the challenge of critical care.
AB  - As she progresses through the final year of her adult nurse education, Selina
      Reyes writes about her placements in a critical care unit, and in district and
      community nursing. 

PMID- 25757591
TI  - Parents of children conceived through assisted conception.
AB  - Parental responsibility allows parents to exercise rights over their children and
      to make decisions on behalf of the child that are in the best interests of the
      welfare of the child. It is a crucial part of being a parent. In recognition of
      the changing demographic of the family resulting in more cohabiting couples and
      step families the law relating to parental responsibility was changed in 2003 and
      2005. With the development of more effective assisted conception techniques and
      increased use of 'do-it-yourself ' insemination using semen purchased over the
      Internet it was necessary to amend the rules relating to parenthood as a result
      of assisted conception. This article considers the amendments relating to the
      recognition of parenthood introduced by the Human Fertilisation and Embryology
      Act 2008. 

PMID- 25757592
TI  - Schwartz Rounds: our experience.

PMID- 25757593
TI  - Hesperidin supplementation modulates inflammatory responses following myocardial
      infarction.
AB  - OBJECTIVE: A growing number of studies have suggested a crucial role for a
      variety of inflammatory mediators in myocardial infarction. Recently, several
      flavonoids have been shown to have cardioprotective and anti-inflammatory
      properties. Therefore, the aim of this study was to investigate the effect of
      hesperidin-a common constituent of citrus fruits-on the serum levels of
      inflammatory markers and adipocytocines in patients with myocardial infarction.
      METHODS: Seventy-five patients with myocardial infarction were participated in
      this randomized, double-blind controlled clinical trial and were assigned to 2
      intervention and control groups. Subjects consumed 600 mg/d pure hesperidin
      supplement and placebo in the intervention and control groups, respectively, for
      4 weeks. Serum concentrations of inflammatory markers and adipocytocines were
      measured at baseline and at the end of the intervention. RESULTS: Consumption of
      600 mg/day hesperidin significantly decreased the serum levels of E-selectin and
      increased adiponectin and high-density lipoprotein cholesterol (HDL-C)
      concentrations in patients with myocardial infarction. The improvement in other
      inflammatory markers, such as interleukin (IL)-6, high-sensitivity C-reactive
      protein (hs-CRP), leptin, and other lipid profile was also observed at the end of
      the intervention, compared to the baseline values, but the difference between the
      hesperidin and placebo groups was not statistically significant (p > 0.05).
      CONCLUSION: Hesperidin supplementation could compensate for decreased levels of
      adiponectin and HDL-C and increased levels of E-selectin in patients with
      myocardial infarction. These results support the concept that certain flavonoids
      in the diet can be associated with significant health benefits, including heart
      health.

PMID- 25757595
TI  - Efficient asymmetric synthesis of structurally diverse P-stereogenic
      phosphinamides for catalyst design.
AB  - The use of chiral phosphinamides is relatively unexplored because of the lack of
      a general method for the synthesis. Reported herein is the development of a
      general, efficient, and highly enantioselective method for the synthesis of
      structurally diverse P-stereogenic phosphinamides. The method relies on
      nucleophilic substitution of a chiral phosphinate derived from the versatile
      chiral phosphinyl transfer agent 1,3,2-benzoxazaphosphinine-2-oxide. These chiral
      phosphinamides were utilized for the first synthesis of readily tunable P
      stereogenic Lewis base organocatalysts, which were used successfully for highly
      enantioselective catalysis. 

PMID- 25757596
TI  - Dual roles of autologous CD8+ T cells in hematopoietic progenitor cell
      mobilization and engraftment.
AB  - BACKGROUND: Poor marrow cellularity alone cannot explain poor hematopoietic
      progenitor cell (HPC) mobilization. This study assessed the role of CD8+ T cells
      in HPC cell mobilization and engraftment. STUDY DESIGN AND METHODS: Mobilization
      and engraftment were assessed in 192 autologous HPC donors. CD34+, CD4+, and CD8+
      T-cell contents in apheresis products were evaluated. Using a chemotaxis assay,
      we assessed the effect of purified autologous CD8+ T cells from low and high
      mobilizers on HPC migration from high to low stromal cell-derived factor (SDF
      1alpha) concentration gradients. We also assessed CD8+ T-cell content association
      with days to neutrophil engraftment. RESULTS: The median number of CD34+ cells/kg
      was 4.7 * 10(6) . Patients were categorized according to their total CD34+ cell
      collection quartile distribution into low, moderate, and high mobilizers. We
      found that HPC products from low mobilizers contained more CD8+ T cells than HPC
      products from moderate and high mobilizers. Chemotaxis assays showed depletion of
      CD8+ T cells enhances HPC mobilization independent of SDF-1alpha concentration.
      Neutrophil engraftment analysis showed that the higher the CD8+ T-cell content
      per unit CD34+ cell, the faster the rate of engraftment. CONCLUSION: Our findings
      suggest CD8+ T cells inhibit HPC mobilization and facilitate homing and
      engraftment.

PMID- 25757594
TI  - Relation between TLR4/NF-kappaB signaling pathway activation by 27
      hydroxycholesterol and 4-hydroxynonenal, and atherosclerotic plaque instability.
AB  - It is now thought that atherosclerosis, although due to increased plasma lipids,
      is mainly the consequence of a complicated inflammatory process, with immune
      responses at the different stages of plaque development. Increasing evidence
      points to a significant role of Toll-like receptor 4 (TLR4), a key player in
      innate immunity, in the pathogenesis of atherosclerosis. This study aimed to
      determine the effects on TLR4 activation of two reactive oxidized lipids carried
      by oxidized low-density lipoproteins, the oxysterol 27-hydroxycholesterol (27-OH)
      and the aldehyde 4-hydroxynonenal (HNE), both of which accumulate in
      atherosclerotic plaques and play a key role in the pathogenesis of
      atherosclerosis. Secondarily, it examined their potential involvement in
      mediating inflammation and extracellular matrix degradation, the hallmarks of
      high-risk atherosclerotic unstable plaques. In human promonocytic U937 cells,
      both 27-OH and HNE were found to enhance cell release of IL-8, IL-1beta, and TNF
      alpha and to upregulate matrix metalloproteinase-9 (MMP-9) via TLR4/NF-kappaB
      dependent pathway; these actions may sustain the inflammatory response and matrix
      degradation that lead to atherosclerotic plaque instability and to their rupture.
      Using specific antibodies, it was also demonstrated that these inflammatory
      cytokines increase MMP-9 upregulation, thus enhancing the release of this matrix
      degrading enzyme by macrophage cells and contributing to plaque instability.
      These innovative results suggest that, by accumulating in atherosclerotic
      plaques, the two oxidized lipids may contribute to plaque instability and
      rupture. They appear to do so by sustaining the release of inflammatory molecules
      and MMP-9 by inflammatory and immune cells, for example, macrophages, through
      activation of TLR4 and its NF-kappaB downstream signaling. 

PMID- 25757597
TI  - Mating type-dependent partner sensing as mediated by VEL1 in Trichoderma reesei.
AB  - Sexual development in the filamentous model ascomycete Trichoderma reesei (syn.
      Hypocrea jecorina) was described only a few years ago. In this study, we show a
      novel role for VELVET in fungi, which links light response, development and
      secondary metabolism. Vel1 is required for mating in darkness, normal growth and
      conidiation. In light, vel1 was dispensable for male fertility but essential for
      female fertility in both mating types. VEL1 impacted regulation of the pheromone
      system (hpr1, hpr2, hpp1, ppg1) in a mating type-dependent manner and depending
      on the mating partner of a given strain. These partner effects only occurred for
      hpp1 and hpr2, the pheromone precursor and receptor genes associated with the
      MAT1-2 mating type and for the mating type gene mat1-2-1. Analysis of secondary
      metabolite patterns secreted by wild type and mutants under asexual and sexual
      conditions revealed that even in the wild type, the patterns change upon
      encounter of a mating partner, with again distinct differences for wild type and
      vel1 mutants. Hence, T. reesei applies a language of pheromones and secondary
      metabolites to communicate with mating partners and that this communication is at
      least in part mediated by VEL1. 

PMID- 25757599
TI  - Ebola vaccines based on adenovirus vectors and risk of HIV.

PMID- 25757598
TI  - The coming of age of engineered multivalent antibodies.
AB  - The development of monoclonal antibody (mAb) technology has had a profound impact
      on medicine. The therapeutic use of first-generation mAb achieved considerable
      success in the treatment of major diseases, including cancer, inflammation,
      autoimmune, cardiovascular, and infectious diseases. Next-generation antibodies
      have been engineered to further increase potency, improve the safety profile and
      acquire non-natural properties, and constitute a thriving area of mAb research
      and development. Currently, a variety of alternative antibody formats with
      modified architectures have been generated and are moving fast into the clinic.
      In fact, the bispecific antibody blinatumomab was the first in its class to be
      approved by the US Food and Drug Administration (FDA) as recently as December
      2014. Here, we outline the fundamental strategies used for designing the next
      generation of therapeutic antibodies, as well as the most relevant results
      obtained in preclinical studies and clinical trials. 

PMID- 25757600
TI  - Campylobacter-Acanthamoeba interactions.
AB  - Campylobacter jejuni is a foodborne pathogen recognized as the major cause of
      human bacterial enteritis. Undercooked poultry products and contaminated water
      are considered as the most important sources of infection. Some studies suggest
      transmission and survival of this bacterial pathogen may be assisted by the free
      living protozoa Acanthamoeba. The latter is known to play the role of a host for
      various pathogenic bacteria, protecting them from harsh environmental conditions.
      Importantly, there is a similarity between the mechanisms of bacterial survival
      within amoebae and macrophages, making the former a convenient tool for the
      investigation of the survival of pathogenic bacteria in the environment. However,
      the molecular mechanisms involved in the interaction between Campylobacter and
      Acanthamoeba are not well understood. Whilst some studies suggest the ability of
      C. jejuni to survive within the protozoa, the other reports support an
      extracellular mode of survival only. In this review, we focus on the studies
      investigating the interaction between Campylobacter and Acanthamoeba, address
      some reasons for the contradictory results, and discuss possible implications of
      these results for epidemiology. Additionally, as the molecular mechanisms
      involved remain unknown, we also suggest possible factors that may be involved in
      this process. Deciphering the molecular mechanisms of pathogen-protozoa
      interaction will assist in a better understanding of Campylobacter lifestyle and
      in the development of novel antibacterial drugs. 

PMID- 25757601
TI  - Dietary fenofibrate reduces hepatic lipid deposition by regulating lipid
      metabolism in yellow catfish Pelteobagrus fulvidraco exposed to waterborne Zn.
AB  - Fenofibrate is known to possess lipid-lowering effects by regulation of gene
      transcription involved in lipid metabolism. Waterborne Zn exposure induces lipid
      deposition in yellow catfish Pelteobagrus fulvidraco. Thus, the present working
      hypothesis is that dietary fenofibrate addition will reduce hepatic lipids in
      yellow catfish exposed to waterborne Zn. To this end, juvenile yellow catfish
      were exposed to 0.04 (control), 0.35 mg/L waterborne Zn, 0.15% dietary
      fenofibrate, and 0.35 mg Zn/l + 0.15% dietary fenofibrate for 8 weeks. Growth
      performance, lipid deposition and metabolism in the liver were determined.
      Dietary fenofibrate promoted growth performance and reduced hepatic lipid content
      of yellow catfish exposed to waterborne Zn. However, these effects did not appear
      in fish in normal water. The lipid-lowering effect of fenofibrate on fish exposed
      to waterborne Zn was associated with increased lipolysis, as indicated by
      increased CPT I activities and expression of lipolytic genes PPARalpha, CPT IA,
      ATGL and HSL, and with reduced lipogenesis as indicated by reduced activities of
      G6PD, 6PGD, ME and ICDH. Dietary fenofibrate significantly increased mRNA levels
      of FAS, LPL and ACCalpha, but reduced mRNA levels of ACCbeta and PPARgamma in
      fish exposed to waterborne Zn. Pearson correlations between transcriptional
      factors expression, and activities and expression of several enzymes were
      observed, indicating that changes at the molecular and enzymatic levels may
      underlie the patterns of lipid metabolism and accordingly affect hepatic fat
      storage. Taken together, our results suggest that the lipid-lowering effect of
      fenofibrate was attributed, in part, to the down-regulation of lipogenesis and up
      regulation of fatty acid oxidation.

PMID- 25757602
TI  - Comparison of Enzymatic Hydrolysis and Acid Hydrolysis of Sterol Glycosides from
      Foods Rich in Delta(7)-Sterols.
AB  - In this study, we present the difference in sterol composition of extracted
      steryl glycosides (SG) hydrolyzed by either enzymatic or acid hydrolysis. SG were
      analyzed from foods belonging to the plant families Cucurbitaceae (melon and
      pumpkin seeds) and Amaranthaceae (amaranth and beetroot), both of which are
      dominated by Delta(7)-sterols. Released sterols were quantified by gas
      chromatography with a flame ionization detector (GC-FID) and identified using gas
      chromatography/mass spectrometry (GC-MS). All Delta(7)-sterols identified
      (Delta(7)-stigmastenyl, spinasteryl, Delta(7)-campesteryl, Delta(7)-avenasteryl,
      poriferasta-7,25-dienyl and poriferasta-7,22,25-trienyl glucoside) underwent
      isomerization under acidic conditions and high temperature. Sterols with an
      ethylidene or methylidene side chain were found to form multiple artifacts. The
      artifact sterols coeluted with residues of incompletely isomerized Delta(7)
      sterols, or Delta(5)-sterols if present, and could be identified as Delta(8(14))
      sterols on the basis of relative retention time, and their MS spectra as
      trimethylsilyl (TMS) and acetate derivatives. For instance, SG from melon were
      composed of 66% Delta(7)-stigmastenol when enzymatic hydrolysis was performed,
      whereas with acid hydrolysis only 8% of Delta(7)-stigmastenol was determined. The
      artifact of Delta(7)-stigmastenol coeluted with residual non-isomerized
      spinasterol, demonstrating the high risk of misinterpretation of compositional
      data obtained after acid hydrolysis. Therefore, the accurate composition of SG
      from foods containing sterols with a double bond at C-7 can only be obtained by
      enzymatic hydrolysis or by direct analysis of the intact SG.

PMID- 25757603
TI  - New approaches to the synthesis of sildenafil analogues and their enzyme
      inhibitory activity.
AB  - In the search for new biologically active chemotypes, several sildenafil analogs
      were prepared and characterized. The presence of the pyrazolo[4,3
      e][1,2,4]triazine core is thought to be of interest for the enzyme inhibitory
      activity of these compounds. The designed derivatives incorporating the
      sildenafil scaffold were assayed as carbonic anhydrase inhibitors, and for their
      cytotoxic activity against MCF-7 and K562 cell lines. The X-ray analysis of one
      of these model compounds was performed and its crystal structure is
      described/compared to that of sildenafil. 

PMID- 25757604
TI  - (18)F-AmBF3-MJ9: a novel radiofluorinated bombesin derivative for prostate cancer
      imaging.
AB  - A novel radiofluorinated derivative of bombesin, (18)F-AmBF3-MJ9, was synthesized
      and evaluated for its potential to image prostate cancer by targeting the gastrin
      releasing peptide receptor (GRPR). AmBF3-MJ9 was prepared from an ammoniomethyl
      trifluoroborate (AmBF3) conjugated alkyne 2 and azidoacetyl-MJ9 via a copper
      catalyzed click reaction, and had good binding affinity for GRPR (Ki=0.5+/
      0.1nM). The (18)F-labeling was performed via a facile one-step (18)F-(19)F
      isotope exchange reaction, and (18)F-AmBF3-MJ9 was obtained in 23+/-5% (n=3)
      radiochemical yield in 25min with >99% radiochemical purity and 100+/-32GBq/MUmol
      specific activity. (18)F-AmBF3-MJ9 was stable in mouse plasma, and was partially
      (22-30%) internalized after binding to GRPR. Positron emission tomography (PET)
      imaging and biodistribution studies in mice showed fast renal excretion and good
      uptake of (18)F-AmBF3-MJ9 by GRPR-expressing pancreas and PC-3 prostate cancer
      xenografts. Tumor uptake was 1.37+/-0.25%ID/g at 1h, and 2.20+/-0.13%ID/g at 2h
      post-injection (p.i.) with low background uptake and excellent tumor
      visualization (tumor-to-muscle ratios of 75.4+/-5.5). These data suggest that
      (18)F-AmBF3-MJ9 is a promising PET tracer for imaging GRPR-expressing prostate
      cancers. 

PMID- 25757605
TI  - Contribution of surface polysaccharides to the resistance of Campylobacter jejuni
      to antimicrobial phenolic compounds.

PMID- 25757606
TI  - Novel autophagy inducers lentztrehaloses A, B and C.
AB  - Trehalose has widespread use as a sweetener, humectant and stabilizer, and is now
      attracting attention as a promising candidate for the treatment of
      neurodegenerative diseases as it is an autophagy inducer and chemical chaperone.
      However, the bioavailability of trehalose is low because it is digested by the
      hydrolyzing enzyme trehalase, expressed in the intestine and kidney. Enzyme
      stable analogs of trehalose would potentially solve this problem. We have
      previously reported an enzyme-stable analog of trehalose, lentztrehalose, and
      herein report two new analogs. The original lentztrehalose has been renamed
      lentztrehalose A and the analogs named lentztrehaloses B and C. Lentztrehalose B
      is a di-dehydroxylated analog and lentztrehalose C is a cyclized analog of
      lentztrehalose A. All the lentztrehaloses are only minimally hydrolyzed by
      mammalian trehalase. The production of the lentztrehaloses is high in rather dry
      conditions and low in wet conditions. Lentztrehalose B shows a moderate
      antioxidative activity. These facts suggest that the lentztrehaloses are produced
      as humectants or protectants for the producer microorganism under severe
      environmental conditions. All the lentztrehaloses induce autophagy in human
      cancer cells at a comparable level to trehalose. Considering the enzyme
      stability, these lentztrehaloses can be regarded as promising new drug candidates
      for the treatment of neurodegenerative diseases and other autophagy-related
      diseases, such as diabetes, arteriosclerosis, cancer and heart disease. 

PMID- 25757607
TI  - Treatment with prolonged-release oxycodone/naloxone improves pain relief and
      opioid-induced constipation compared with prolonged-release oxycodone in patients
      with chronic severe pain and laxative-refractory constipation.
AB  - PURPOSE: Laxative-refractory opioid-induced constipation (OIC) is defined as OIC
      despite using 2 laxatives with a different mechanism of action (based on the
      Anatomical Therapeutic Chemical Classification System level 4 term [contact
      laxatives, osmotically acting laxatives, softeners/emollients, enemas, and
      others]). OIC has a significant impact on the treatment and quality of life of
      patients with severe chronic pain. This noninterventional, observational, real
      life study in Belgium investigated the efficacy of prolonged-release
      oxycodone/naloxone combination (PR OXN) treatment regarding pain relief and OIC
      compared with previous prolonged-release oxycodone (PR OXY) treatment for
      laxative-refractory OIC in daily clinical practice. METHODS: Laxative-refractory
      OIC patients with severe chronic pain were treated with PR OXN for 12 weeks (3
      visits). Pain relief (assessed on a numerical rating scale) and OIC (assessed by
      using the Bowel Function Index [BFI]) were evaluated at each visit. A responder
      was defined as a patient who had: (1) no worsening of pain at the last visit
      compared with visit 1 or a numerical rating scale <=4 at visit 3/last visit; and
      (2) a reduction in BFI >=12 units at visit 3/last visit compared with visit 1; or
      (3) a BFI <=28.8 at visit 3/last visit. FINDINGS: Sixty-eight laxative-refractory
      OIC patients with severe chronic pain (mean (sd) age 59.8 (13.3) years, 67.6%
      female and 91.2% non-malignant pain) were treated for 91 days with PR OXN (median
      daily dose, 20 mg). Treatment with PR OXN resulted in a significant and
      clinically relevant decrease of pain of 2.1 units (P < 0.001; 95% CI, 1.66-2.54)
      and of BFI by 48.5 units (P < 0.001; 95% CI, 44.4-52.7) compared with PR OXY
      treatment; use of laxatives was also significantly reduced (P < 0.001).
      Approximately 95% of patients were responders, and quality of life (as measured
      by using the EQ-5D) improved significantly. Adverse events were opioid related,
      and PR OXN treatment was well tolerated. IMPLICATIONS: Treatment with PR OXN
      resulted in a significant and clinically relevant reduction in OIC compared with
      previous PR OXY treatment for these patients with severe chronic pain and
      laxative-refractory OIC. Treatment with PR OXN also resulted in a significant
      improvement in pain relief and quality of life. ClinicalTrials.gov identifier:
      NCT01710917.

PMID- 25757609
TI  - Palmar arch anatomy: Ajmer Working Group classification.
AB  - INTRODUCTION: Forearm arteries are frequently used as workhorse site for cardiac
      catheterization, bypass grafting and haemodialysis access. There is paucity of
      data on palmar circulation in live human being and only cadaveric data are
      available till date. We, therefore, made an attempt to look at the various
      patterns of sufficient or insufficient palmar arch circulation and various
      anomalies of forearm arteries, to discuss their clinical implications. METHODS
      AND RESULTS: We obtained the forearm and hand arteriograms of patients (n = 302)
      through radial (n = 200) and ulnar routes (n = 102). Modified Allen's test was
      normal in all of our patients. On the basis of predetermined parameters
      angiograms were analysed and findings were divided into three groups. These three
      groups were further classified as type A, type B, type C superficial palmar arch.
      CONCLUSION: We concluded that type A superficial palmar arch is most suitable for
      providing adequate collateral circulation in case of harvesting of forearm
      vessel, whereas type C superficial palmar arch appears to be highly susceptible
      for digital ischemia in case of radial or ulnar artery occlusion. Modified
      Allen's test alone is not justifiable for documenting good collateral circulation
      and it should be supplemented by other tests to document good collateral
      circulation before proceeding to any radical procedure.

PMID- 25757611
TI  - HRT increases risk of blood clots and stroke, finds new analysis.

PMID- 25757612
TI  - Perineural granulomas in cutaneous sarcoidosis may be associated with sarcoidosis
      small-fiber neuropathy.
AB  - Perineural granulomas in cutaneous sarcoidosis have been rarely reported and
      their clinical significance has yet to be evaluated. Recently, a 27-year-old male
      presented with multiple pink papules on the flank and lower back, accompanied by
      a painful, burning sensation. Biopsies revealed well-defined granulomas,
      consistent with sarcoidosis, in the dermis and involving small cutaneous nerves.
      We hypothesized that perineural granulomas may be an under-recognized feature of
      cutaneous sarcoidosis and may be responsible for sensory disturbances. We
      reviewed cases from 29 consecutive patients with cutaneous sarcoidosis.
      Perineural granulomas were identified in 18/29 (62%) patients and in 22/40 (55%)
      biopsies. Perineural granulomas were identified in 7/9 biopsies from the proximal
      upper extremity, 1/3 from the distal upper extremity, 7/12 from the head and the
      neck, including 4/4 from the nose, 5/9 from the back, 1/2 from the flank and 1/1
      from the proximal lower extremity and 0/4 from the distal lower extremity. The
      anatomical distribution is similar to sarcoidosis small-fiber neuropathy (SSFN),
      in which sarcoidosis patients without evident skin lesions experience sensory
      disturbances of unknown etiology involving the face, the proximal extremities and
      the trunk. Our results indicate perineural granulomas in cutaneous sarcoidosis
      are more common than previously appreciated, primarily involve the head, the
      proximal upper extremities and the back, and may be responsible for neurological
      manifestations. 

PMID- 25757610
TI  - Tracking the best reference genes for RT-qPCR data normalization in filamentous
      fungi.
AB  - BACKGROUND: A critical step in the RT-qPCR workflow for studying gene expression
      is data normalization, one of the strategies being the use of reference genes.
      This study aimed to identify and validate a selection of reference genes for
      relative quantification in Talaromyces versatilis, a relevant industrial
      filamentous fungus. Beyond T. versatilis, this study also aimed to propose
      reference genes that are applicable more widely for RT-qPCR data normalization in
      filamentous fungi. RESULTS: A selection of stable, potential reference genes was
      carried out in silico from RNA-seq based transcriptomic data obtained from T.
      versatilis. A dozen functionally unrelated candidate genes were analysed by RT
      qPCR assays over more than 30 relevant culture conditions. By using geNorm, we
      showed that most of these candidate genes had stable transcript levels in most of
      the conditions, from growth environments to conidial germination. The overall
      robustness of these genes was explored further by showing that any combination of
      3 of them led to minimal normalization bias. To extend the relevance of the study
      beyond T. versatilis, we challenged their stability together with sixteen other
      classically used genes such as beta-tubulin or actin, in a representative sample
      of about 100 RNA-seq datasets. These datasets were obtained from 18
      phylogenetically distant filamentous fungi exposed to prevalent experimental
      conditions. Although this wide analysis demonstrated that each of the chosen
      genes exhibited sporadic up- or down-regulation, their hierarchical clustering
      allowed the identification of a promising group of 6 genes, which presented weak
      expression changes and no tendency to up- or down-regulation over the whole set
      of conditions. This group included ubcB, sac7, fis1 and sarA genes, as well as
      TFC1 and UBC6 that were previously validated for their use in S. cerevisiae.
      CONCLUSIONS: We propose a set of 6 genes that can be used as reference genes in
      RT-qPCR data normalization in any field of fungal biology. However, we recommend
      that the uniform transcription of these genes is tested by systematic
      experimental validation and to use the geometric averaging of at least 3 of the
      best ones. This will minimize the bias in normalization and will support
      trustworthy biological conclusions.

PMID- 25757613
TI  - Gene therapies for hepatitis C virus.
AB  - Hepatitis C virus (HCV) is a leading cause of chronic hepatitis and infects
      approximately three to four million people per year, about 170 million infected
      people in total, making it one of the major global health problems. In a minority
      of cases HCV is cleared spontaneously, but in most of the infected individuals
      infection progresses to a chronic state associated with high risk to develop
      liver cirrhosis, hepatocellular cancer, or liver failure. The treatment of HCV
      infection has evolved over the years. Interferon (IFN)-alpha in combination with
      ribavirin has been used for decades as standard therapy. More recently, a new
      standard-of-care treatment has been approved based on a triple combination with
      either HCV protease inhibitor telaprevir or boceprevir. In addition, various
      options for all-oral, IFN-free regimens are currently being evaluated. Despite
      substantial improvement of sustained virological response rates, some intrinsic
      limitations of these new direct-acting antivirals, including serious side
      effects, the risk of resistance development and high cost, urge the development
      of alternative or additional therapeutic strategies. Gene therapy represents a
      feasible alternative treatment. Small RNA technology, including RNA interference
      (RNAi) techniques and antisense approaches, is one of the potentially promising
      ways to investigate viral and host cell factors that are involved in HCV
      infection and replication. With this, newly developed gene therapy regimens will
      be provided to treat HCV. In this chapter, a comprehensive overview guides you
      through the current developments and applications of RNAi and microRNA-based gene
      therapy strategies in HCV treatment. 

PMID- 25757614
TI  - Recent advances in use of gene therapy to treat hepatitis B virus infection.
AB  - Chronic infection with hepatitis B virus (HBV) occurs in approximately 5 % of the
      world's human population and persistence of the virus is associated with serious
      complications of cirrhosis and liver cancer. Currently available treatments are
      modestly effective and advancing novel therapeutic strategies is a medical
      priority. Stability of the viral cccDNA replication intermediate is a major
      factor that has impeded the development of therapies that are capable of
      eliminating chronic infection. Recent advances that employ gene therapy
      strategies offer useful advantages over current therapeutics. Silencing of HBV
      gene expression by harnessing the RNA interference pathway has been shown to be
      highly effective in cell culture and in vivo. However, a potential limitation of
      this approach is that the post-transcriptional mechanism of gene silencing does
      not disable cccDNA. Early results using designer transcription activator-like
      effector nucleases (TALENs) and repressor TALEs (rTALEs) have shown potential as
      a mode of inactivating cccDNA. In this article, we review the recent advances
      that have been made in HBV gene therapy, with a particular emphasis on the
      potential anti-HBV therapeutic utility of designed sequence-specific DNA binding
      proteins and their derivatives. 

PMID- 25757615
TI  - U1 interference (U1i) for antiviral approaches.
AB  - U1 snRNP (U1 small nuclear ribonucleoprotein) is an essential component of the
      splicing machinery. U1 snRNP also plays an additional role in 3'-end mRNA
      processing when it binds close to polyadenylation sites (PAS).
      Cotranscriptionally, U1 snRNP binding close to putative PAS prevents premature
      cleavage and polyadenylation and consequently safeguards pre-mRNA transcripts and
      defines promoter directionality. At the 3'-end of mRNAs, U1 snRNP binding to
      putative PAS may regulate mRNA length or inhibit polyadenylation and, therefore,
      gene expression. U1 interference (U1i) is a technique to inhibit gene expression
      based on the property of U1 snRNP to inhibit polyadenylation. It requires the
      expression of a modified U1 snRNP, which interacts with a target gene upstream of
      its PAS and inhibits target gene expression. U1i has been used to inhibit the
      expression of reporter or endogenous genes both in tissue culture and in animal
      models. In addition, U1i combination with RNA interference (RNAi), another RNA
      based gene silencing technology, results in a synergistic increased inhibition.
      This is of special interest for antiviral therapy, where strong inhibitions may
      be required to decrease the expression of replicative viral RNAs and impact the
      replication cycle. Furthermore, the combination of U1i and RNAi-based inhibitors
      should prevent the appearance of viral variants resistant to the treatment and
      allows the dose of inhibitors to be decreased and a functional inhibition to be
      obtained with fewer off target effects. In fact, U1i has been used to inhibit the
      expression of HIV-1 and HBV, whose viral genomes express mRNAs that must be
      polyadenylated by the nuclear polyadenylation machinery. In the case of HBV,
      antiviral U1i has been combined with RNAi to demonstrate a strong inhibition of
      expression from HBV sequences in vivo. This shows that, although several aspects
      of U1i technology remain to be addressed, U1i and U1i combined with RNAi have
      great potential as antivirals. 

PMID- 25757616
TI  - Gene therapy strategies to block HIV-1 replication by RNA interference.
AB  - The cellular mechanism of RNA interference (RNAi) plays an antiviral role in many
      organisms and can be used for the development of therapeutic strategies against
      viral pathogens. Persistent infections like the one caused by the human
      immunodeficiency virus type 1 (HIV-1) likely require a durable gene therapy
      approach. The continuous expression of the inhibitory RNA molecules in T cells is
      needed to effectively block HIV-1 replication. We discuss here several issues,
      ranging from the choice of RNAi inhibitor and vector system, finding the best
      target in the HIV-1 RNA genome, alternatively by targeting host mRNAs that encode
      important viral cofactors, to the setup of appropriate preclinical test systems.
      Finally, we briefly discuss the relevance of this topic for other viral pathogens
      that cause a chronic infection in humans. 

PMID- 25757617
TI  - HIV and Ribozymes.
AB  - Ribozymes are structured RNA molecules that act as catalysts in different
      biological reactions. From simple genome cleaving activities in satellite RNAs to
      more complex functions in cellular protein synthesis and gene regulation,
      ribozymes play important roles in all forms of life. Several naturally existing
      ribozymes have been modified for use as therapeutics in different conditions,
      with HIV-1 infection being one of the most studied. This chapter summarizes data
      from different preclinical and clinical studies conducted to evaluate the
      potential of ribozymes to be used in HIV-1 therapies. The different ribozyme
      motifs that have been modified, as well as their target sites and expression
      strategies, are described. RNA conjugations used to enhance the antiviral effect
      of ribozymes are also presented and the results from clinical trials conducted to
      date are summarized. Studies on anti-HIV-1 ribozymes have provided valuable
      information on the optimal expression strategies and clinical protocols for RNA
      gene therapy and remain competitive candidates for future therapy. 

PMID- 25757618
TI  - Editing CCR5: a novel approach to HIV gene therapy.
AB  - Acquired immunodeficiency syndrome (AIDS) is a life-threatening disorder caused
      by infection of individuals with the human immunodeficiency virus (HIV). Entry of
      HIV-1 into target cells depends on the presence of two surface proteins on the
      cell membrane: CD4, which serves as the main receptor, and either CCR5 or CXCR4
      as a co-receptor. A limited number of people harbor a genomic 32-bp deletion in
      the CCR5 gene (CCR5?32), leading to expression of a truncated gene product that
      provides resistance to HIV-1 infection in individuals homozygous for this
      mutation. Moreover, allogeneic hematopoietic stem cell (HSC) transplantation with
      CCR5?32 donor cells seems to confer HIV-1 resistance to the recipient as well.
      However, since Delta32 donors are scarce and allogeneic HSC transplantation is
      not exempt from risks, the development of gene editing tools to knockout CCR5 in
      the genome of autologous cells is highly warranted. Targeted gene editing can be
      accomplished with designer nucleases, which essentially are engineered
      restriction enzymes that can be designed to cleave DNA at specific sites. During
      repair of these breaks, the cellular repair pathway often introduces small
      mutations at the break site, which makes it possible to disrupt the ability of
      the targeted locus to express a functional protein, in this case CCR5. Here, we
      review the current promise and limitations of CCR5 gene editing with engineered
      nucleases, including factors affecting the efficiency of gene disruption and
      potential off-target effects. 

PMID- 25757619
TI  - Synthetic DNA approach to cytomegalovirus vaccine/immune therapy.
AB  - There is no licensed vaccine or cure for human cytomegalovirus (CMV), a
      ubiquitous beta-herpes virus that infects 60-95 % of adults worldwide. Infection
      is a major cause of congenital abnormalities in newborns, contributes to
      development of childhood cerebral palsy and medulloblastoma, can result in severe
      disease in immunocompromised patients, and is a major impediment during
      successful organ transplantation. While CMV has been increasingly associated with
      numerous inflammatory diseases and cancers, only recently has it been correlated
      with increased risk of heart disease in adults, the number-one killer in the USA.
      These data, among others, suggest that subclinical CMV infection, or
      microinfection, in healthy individuals may play more of a causative role than an
      epiphenomenon in development of CMV-associated pathologies. Due to the myriad of
      diseases and complications associated with CMV, an efficacious vaccine would be
      highly valuable in reducing human morbidity and mortality as well as saving
      billions of dollars in annual health-care costs and disability adjusted life
      years (DALY) in the developing world. Therefore, the development of a safe
      efficacious CMV vaccine or immune therapy is paramount to the public health. This
      review aims to provide a brief overview on aspects of CMV infection and disease
      and focuses on current vaccine strategies. The use of new synthetic DNA vaccines
      might offer one such approach to this difficult problem. 

PMID- 25757620
TI  - Vector-mediated antibody gene transfer for infectious diseases.
AB  - This chapter discusses the emerging field of vector-mediated antibody gene
      transfer as an alternative vaccine for infectious disease, with a specific focus
      on HIV. However, this methodology need not be confined to HIV-1; the general
      strategy of vector-mediated antibody gene transfer can be applied to other
      difficult vaccine targets like hepatitis C virus, malaria, respiratory syncytial
      virus, and tuberculosis. This approach is an improvement over classical passive
      immunization strategies that administer antibody proteins to the host to provide
      protection from infection. With vector-mediated gene transfer, the antibody gene
      is delivered to the host, via a recombinant adeno-associated virus (rAAV) vector;
      this in turn results in long-term endogenous antibody expression from the
      injected muscle that confers protective immunity. Vector-mediated antibody gene
      transfer can rapidly move existing, potent broadly cross-neutralizing HIV-1
      specific antibodies into the clinic. The gene transfer products demonstrate a
      potency and breadth identical to the original product. This strategy eliminates
      the need for immunogen design and interaction with the adaptive immune system to
      generate protection, a strategy that so far has shown limited promise. 

PMID- 25757621
TI  - HIV Latency and the noncoding RNA therapeutic landscape.
AB  - The Human Immunodeficiency Virus (HIV) belongs to the subfamily of lentiviruses
      that are characterized by long incubation periods and chronic, persistent
      infection. The virus integrates into the genome of infected CD4+ cells and, in a
      subpopulation of cells, adopts a transcriptionally silent state, a process
      referred to a viral latency. This property makes it exceedingly difficult to
      therapeutically target the virus and eradicate infection. If left untreated, the
      inexorable demise of the infected individual's immune system ensues, a causal
      result of Acquired Immunodeficiency Syndrome (AIDS). Latently infected cells
      provide a reservoir that maintains viral infection indefinitely. In this chapter
      we explore the role of noncoding RNAs in HIV infection and in the establishment
      and maintenance of viral latency. Both short and long noncoding RNAs are
      endogenous modulators of epigenetic regulation in human cells and play an active
      role in gene expression. Lastly, we explore therapeutic modalities based on
      expressed RNAs that are capable of countering infection, transcriptionally
      regulating the virus, and suppressing or activating the latent state. 

PMID- 25757622
TI  - C peptides as entry inhibitors for gene therapy.
AB  - Peptides derived from the C-terminal heptad repeat 2 region of the HIV-1 gp41
      envelope glycoprotein, so-called C peptides, are very potent HIV-1 fusion
      inhibitors. Antiviral genes encoding either membrane-anchored (ma) or secreted
      (iSAVE) C peptides have been engineered and allow direct in vivo production of
      the therapeutic peptides by genetically modified host cells. Membrane-anchored C
      peptides expressed in the HIV-1 target cells by T-cell or hematopoietic stem cell
      gene therapy efficiently prevent virus entry into the modified cells. Such gene
      protection confers a selective survival advantage and allows accumulation of the
      genetically modified cells. Membrane-anchored C peptides have been successfully
      tested in a nonhuman primate model of AIDS and were found to be safe in a phase I
      clinical trial in AIDS patients transplanted with autologous gene-modified T
      cells. Secreted C peptides have the crucial advantage of not only protecting
      genetically modified cells from HIV-1 infection, but also neighboring cells, thus
      suppressing virus replication even if only a small fraction of cells is
      genetically modified. Accordingly, various cell types can be considered as
      potential in vivo producer cells for iSAVE-based gene therapeutics, which could
      even be modified by direct in vivo gene delivery in future. In conclusion, C
      peptide gene therapeutics may provide a strong benefit to AIDS patients and could
      present an effective alternative to current antiretroviral drug regimens. 

PMID- 25757623
TI  - Aptamer-siRNA chimeras for HIV.
AB  - Since 1980s, HIV/AIDS has escalated into a global pandemic. Although
      combinatorial antiretroviral therapy (cART) regimens can suppress plasma virus
      levels to below the detection limit and the survival rate of HIV-1 infected
      patients has been improving, long-term cART holds the potential to cause a number
      of chronic diseases. RNA interference (RNAi) is considered as a powerful method
      for developing new generation of therapeutics. Discovery of small interfering
      RNAs (siRNAs) shed light on limitations of targets that are "undruggable" with
      current technologies. However, delivery remains a major hurdle of siRNA-based
      therapy. Recent progress in technology of engineering nucleic acid enables a
      targeted delivery of siRNAs using aptamers, which, as often regarded as nucleic
      acid "antibodies," can recognize/bind to multiple different proteins and small
      molecule targets by forming scaffolds for molecular interactions. SELEX
      technology enabled to isolate highly target specific aptamers from a random
      sequence oligonucleotide library. A number of aptamers for HIV-1 proteins as well
      as host proteins that interact with HIV-1 have been developed and some of them
      have potent viral neutralization ability and inhibition of HIV-1 infectivity. The
      availability of these aptamers has given an idea of using aptamers for targeting
      delivery of siRNAs. So far, aptamers against either HIV-1 gp120 or CD4 have been
      eagerly evaluated as the aptamer portion of the aptamer-siRNA chimeras for the
      treatment or prevention of HIV-1. In this chapter, we highlight the development
      and therapeutic potential of aptamer-siRNA chimeras for HIV-1. 

PMID- 25757624
TI  - P53 deficiency-induced Smad1 upregulation suppresses tumorigenesis and causes
      chemoresistance in colorectal cancers.
AB  - The DNA damage response helps to maintain genome integrity, suppress
      tumorigenesis, and mediate the effects of radiotherapy and chemotherapy. Our
      previous studies have shown that Smad1 is upregulated and activated by Atm in DNA
      damage response, which can further bind to p53 and promote p53 stabilization.
      Here we report another aspect of the interplay between p53 and Smad1. Comparison
      of rectal tumor against paired paraneoplastic specimens and analysis of >500
      colorectal tumors revealed that Smad1 was upregulated in tumor samples, which was
      attributable to p53 defects. Using MEFs as a model, we found that knockdown of
      the elevated Smad1 in p53(-/-) MEFs promoted cell proliferation, E1A/Ras-induced
      cell transformation, and tumorigenesis. Mechanistic studies suggest that elevated
      Smad1 and momentary activation inhibit cell proliferation by upregulating p57Kip2
      and enhancing Atm-Chk2 activation. Surprisingly, elevated Smad1 appears to have a
      negative effect on chemotherapy, as colorectal tumors, primary cancer cells, and
      cell lines with Smad1 knockdown all showed an increase in chemosensitivity, which
      could be attributable to elevated p57Kip2. These findings underscore the
      significance of Smad1-p53 interaction in tumor suppression and reveal an
      unexpected role for Smad1 in chemoresistance of colorectal cancers. 

PMID- 25757626
TI  - High-throughput microarray mapping of cell wall polymers in roots and tubers
      during the viscosity-reducing process.
AB  - Viscosity reduction has a great impact on the efficiency of ethanol production
      when using roots and tubers as feedstock. Plant cell wall-degrading enzymes have
      been successfully applied to overcome the challenges posed by high viscosity.
      However, the changes in cell wall polymers during the viscosity-reducing process
      are poorly characterized. Comprehensive microarray polymer profiling, which is a
      high-throughput microarray, was used for the first time to map changes in the
      cell wall polymers of sweet potato (Ipomoea batatas), cassava (Manihot
      esculenta), and Canna edulis Ker. over the entire viscosity-reducing process. The
      results indicated that the composition of cell wall polymers among these three
      roots and tubers was markedly different. The gel-like matrix and glycoprotein
      network in the C. edulis Ker. cell wall caused difficulty in viscosity reduction.
      The obvious viscosity reduction of the sweet potato and the cassava was
      attributed to the degradation of homogalacturonan and the released 1,4-beta-d
      galactan and 1,5-alpha-l-arabinan. 

PMID- 25757627
TI  - Response of a chemical wave to local pulse irradiation in the ruthenium-catalyzed
      Belousov-Zhabotinsky reaction.
AB  - The photo-sensitive Belousov-Zhabotinsky (BZ) reaction system was investigated to
      understand the response of wave propagation to local pulse stimulation in an
      excitable field. When the chemical wave was irradiated with a bright pulse or a
      dark pulse, the speed of wave propagation decreased or increased. The timing of
      pulse irradiation that significantly affected the speed of chemical wave
      propagation was different with the bright and dark pulses. That is, there is a
      sensitive point in the chemical wave. The experimental results were qualitatively
      reproduced by a numerical calculation based on a three-variable Oregonator model
      that was modified for the photosensitive BZ reaction. These results suggest that
      the chemical wave is sensitive to the timing of pulse irradiation due to the
      rates of production of an activator and an inhibitor in the photochemical
      reaction. 

PMID- 25757625
TI  - Efficient inversions and duplications of mammalian regulatory DNA elements and
      gene clusters by CRISPR/Cas9.
AB  - The human genome contains millions of DNA regulatory elements and a large number
      of gene clusters, most of which have not been tested experimentally. The
      clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR
      associated nuclease 9 (Cas9) programed with a synthetic single-guide RNA (sgRNA)
      emerges as a method for genome editing in virtually any organisms. Here we report
      that targeted DNA fragment inversions and duplications could easily be achieved
      in human and mouse genomes by CRISPR with two sgRNAs. Specifically, we found
      that, in cultured human cells and mice, efficient precise inversions of DNA
      fragments ranging in size from a few tens of bp to hundreds of kb could be
      generated. In addition, DNA fragment duplications and deletions could also be
      generated by CRISPR through trans-allelic recombination between the Cas9-induced
      double-strand breaks (DSBs) on two homologous chromosomes (chromatids). Moreover,
      junctions of combinatorial inversions and duplications of the protocadherin
      (Pcdh) gene clusters induced by Cas9 with four sgRNAs could be detected. In mice,
      we obtained founders with alleles of precise inversions, duplications, and
      deletions of DNA fragments of variable sizes by CRISPR. Interestingly, we found
      that very efficient inversions were mediated by microhomology-mediated end
      joining (MMEJ) through short inverted repeats. We showed for the first time that
      DNA fragment inversions could be transmitted through germlines in mice. Finally,
      we applied this CRISPR method to a regulatory element of the Pcdhalpha cluster
      and found a new role in the regulation of members of the Pcdhgamma cluster. This
      simple and efficient method should be useful in manipulating mammalian genomes to
      study millions of regulatory DNA elements as well as vast numbers of gene
      clusters. 

PMID- 25757628
TI  - Gastrointestinal complications in renal transplant recipients detected by
      endoscopic biopsies in a developing country.
AB  - BACKGROUND: Renal transplantation is the treatment of choice for patients with
      end-stage renal disease. The renal transplant recipients are susceptible to a
      variety of gastrointestinal (GI) complications such as infections, ulcer disease,
      and malignancies. OBJECTIVES: We aimed to determine the frequency of pathological
      lesions in GI endoscopic biopsies in recipients of live related renal
      transplantation in our setting. METHODS: This retrospective survey was carried
      out at Histopathology Department of Sindh Institute of Urology and
      Transplantation, Karachi, from December 2010 to January 2011. All consecutive
      renal transplant patients of all ages and both genders on regular follow up,
      presenting with GI complaints and in whom GI endoscopic biopsies were performed,
      were included. The demographic, clinical, and laboratory data were retrieved from
      case files and the pathological diagnoses from the original biopsy reports.
      RESULTS: A total of 200 consecutive renal transplant patients were enrolled. The
      biopsies comprised of 19 (9.5 %) esophageal biopsies, 119 (59.5 %) gastric
      biopsies, 148 (74 %) duodenal biopsies, and 66 (33 %) colorectal biopsies. The
      main pathological lesions included cytomegalovirus infection in 22 (11 %) of all
      patients, Helicobacter pylori in 11 (9.2 %) of gastric biopsies, cryptosporidium
      in 4 (1.6 %), giardiasis in 30 (15 %), immunoproliferative small intestinal
      disease in 5 (3.4 %), tropical sprue in 33 (15 %), tuberculosis in 3 (2 %) of the
      small intestinal biopsies, and gastric adenocarcinoma in 1 (1.7 %) gastric
      biopsy. CONCLUSION: A wide spectrum of pathological lesions including
      opportunistic infections was seen in GI endoscopic biopsies in renal transplant
      patients. Endoscopic biopsies play an important role in the diagnosis and
      management of GI disease in renal transplant patients.

PMID- 25757629
TI  - The value of digital tomosynthesis of the chest as a problem-solving tool for
      suspected pulmonary nodules and hilar lesions detected on chest radiography.
AB  - OBJECTIVES: To assess the capability of digital tomosynthesis (DTS) of the chest
      compared to a postero-anterior (PA) and lateral chest radiograph (CXR) in the
      diagnosis of suspected but unconfirmed pulmonary nodules and hilar lesions
      detected on a CXR. Computed tomography (CT) was used as the reference standard.
      MATERIALS AND METHOD: 78 patients with suspected non-calcified pulmonary nodules
      or hilar lesions on their CXR were included in the study. Two radiologists,
      blinded to the history and CT, prospectively analysed the CXR (PA and lateral)
      and the DTS images using a picture archiving and communication workstation and
      were asked to designate one of two outcomes: true intrapulmonary lesion or false
      intrapulmonary lesion. A CT of the chest performed within 4 weeks of the CXR was
      used as the reference standard. Inter-observer agreement and time to report the
      modalities were calculated for CXR and DTS. RESULTS: There were 34 true lesions
      confirmed on CT, 12 were hilar lesions and 22 were peripheral nodules. Of the 44
      false lesions, 37 lesions were artefactual or due to composite shadow and 7
      lesions were real but extrapulmonary simulating non-calcified intrapulmonary
      lesions. The PA and lateral CXR correctly classified 39/78 (50%) of the lesions,
      this improved to 75/78 (96%) with DTS. The sensitivity and specificity was 0.65
      and 0.39 for CXR and 0.91 and 1 for DTS. Based on the DTS images, readers
      correctly classified all the false lesions but missed 3/34 true lesions. Two of
      the missed lesions were hilar in location and one was a peripheral nodule. All
      three missed lesions were incorrectly classified on DTS as composite shadow.
      CONCLUSIONS: DTS improves diagnostic confidence when compared to a repeat PA and
      lateral CXR in the diagnosis of both suspected hilar lesions and pulmonary
      nodules detected on CXR. DTS is able to exclude most peripheral pulmonary nodules
      but caution and further studies are needed to assess its ability to exclude hilar
      lesions.

PMID- 25757630
TI  - Labyrinthitis Ossificans: On the Mechanism of Perilabyrinthine Bone Remodeling.
AB  - INTRODUCTION: It has been suggested that remodeling of the otic capsule is highly
      suppressed by the action of anti-resorptive signals emanating from structures of
      the inner ear space. Labyrinthitis ossificans (LO) is a severe complication to
      bacterial meningitis and is characterized by destruction of inner ear structures
      by the formation of new bone. The aim of this study was to explore the impact of
      LO on bone remodeling of the otic capsule. MATERIAL AND METHODS: In 11 human
      temporal bones with extensive LO and 10 control specimens, the degree of bone
      remodeling was explored indirectly by estimating the viability of osteocytes in
      perilabyrinthine bone and the mastoid. RESULTS: The viability of osteocytes was
      significantly lower in the perilabyrinthine bone compared to the mastoid in both
      groups. However, the loss of perilabyrinthine osteocytes was the same in the 2
      groups, and the presence of cartilage remnants appeared to be the same.
      CONCLUSION: This study indicates that the factors affecting bone remodeling of
      the otic capsule and the degeneration of osteocytes are not altered by wholesale
      destruction of inner ear soft tissue and its replacement by bone. Therefore,
      alternative mechanisms may be implicated in the suppression of capsular bone
      remodeling.

PMID- 25757631
TI  - Potential Advantages of a Single-Port, Operator-Controlled Flexible Endoscope
      System for Transoral Surgery of the Larynx.
AB  - INTRODUCTION: Transoral surgery of the larynx is commonly performed with a rigid
      laryngoscope, a microscope, and a laser. We investigated the potential utility of
      a flexible, single-port, robot-assisted and physician-controlled endoscopic
      system to enable easy, transoral surgical access to the larynx. METHODS:
      Transoral laryngeal surgery was performed in human cadavers (n = 4) using the
      Flex System and compatible flexible instruments. Anatomical landmarks were
      identified, and mock surgical procedures were performed. RESULTS: Standard
      laryngeal surgical procedures were completed successfully in a human cadaver
      model. The built-in HD digital camera enabled high-quality visualization of the
      larynx. Epiglottectomy, as well as posterior cordectomy, were performed by laser
      and radio-frequency resection. The flexible design of the compatible tools
      enabled a nontraumatic approach. CONCLUSION: The Flex System has the potential to
      improve surgical access to the larynx, especially in patients with challenging
      anatomy. The associated flexible instruments enabled completion of surgical
      procedures in the larynx in a human cadaveric model. Further clinical studies, as
      well as the development of supplemental technology and tools, are recommended for
      future clinical applications.

PMID- 25757632
TI  - Use of other treatment before hysterectomy for benign conditions: what about PCS
      and CD10?

PMID- 25757633
TI  - Reply: To PMID 25542564.

PMID- 25757634
TI  - Immediate versus delayed cord clamping.

PMID- 25757635
TI  - Exogenous oxytocin modulates human myometrial microRNAs.
AB  - OBJECTIVE: MicroRNAs (miRNAs) play a modulatory role in pathways that lead to
      labor onset, although oxytocin is known to modulate gene expression within the
      myometrium. We aimed to identify miRNAs whose expression is regulated by oxytocin
      in pregnant human myometrium. STUDY DESIGN: Myometrial miRNA expression profiles
      were compared between samples collected from women at term before the onset of
      labor (no labor; n = 8) and after labor onset after early exogenous oxytocin
      treatment (n = 8). Multivariate modelling was used to assess differences in miRNA
      profiles. Biologic validation was undertaken on 3 independent patient cohorts (no
      labor, n = 10; labor induced with oxytocin, n = 8; and spontaneous labor with no
      oxytocin treatment, n = 10). In vitro studies that used primary myocytes were
      undertaken to assess target miRNA expression after oxytocin treatment. Target
      genes of candidate miRNAs were identified in silico and cross-referenced with
      genes that are known to be associated with labor or expressed in myometrium.
      RESULTS: In total, 1309 miRNAs were analyzed by microarray, of which 494 were
      detected in human myometrium. Multivariate modeling identified 12 target miRNAs
      the differential expression of which was most responsible for the observed
      separation of the 2 patient populations in the primary discovery cohorts.
      Biologic validation in the independent secondary sample cohorts showed that
      oxytocin independently regulated 5 miRNAs (hsa-miR-146b-3p, hsa-miR-196b-3p, hsa
      miR-223-3p, hsa-miR-873-5p, and hsa-miR-876-5p). Additionally, hsa-miR-146b-3p
      was increased both in labor that was induced with oxytocin and in myometrium from
      spontaneous labor with no oxytocin treatment compared with no labor samples. Four
      of the validated miRNAs (hsa-miR-146a-5p, hsa-miR-146b-3p, hsa-miR-196b-3p, and
      hsa-miR-876-5p) were expressed in primary human myocytes; oxytocin treatment of
      these cells replicated the directional changes that were observed in vivo.
      CONCLUSION: Oxytocin alters the expression of a unique set of myometrial miRNAs.
      These results suggest a further role for oxytocin as a signaling molecule that is
      involved in the regulation of gene expression during parturition.

PMID- 25757636
TI  - Omega-3 supplementation to prevent recurrent preterm birth: a systematic review
      and metaanalysis of randomized controlled trials.
AB  - The purpose of this study was to evaluate the efficacy of omega-3 supplementation
      for the prevention of recurrent preterm birth (PTB) in asymptomatic singleton
      gestations with previous PTB. We searched fish oil, long chain polyunsaturated
      fatty acids, pregnancy, and omega-3 in MEDLINE, OVID, Scopus, ClinicalTrials.gov,
      the PROSPERO International Prospective Register of Systematic Reviews, EMBASE,
      and the Cochrane Central Register of Controlled Trials from inception of each
      database to December 2014 with no limit for language. In addition the reference
      lists of all identified articles were examined to identify studies that were not
      captured by electronic searches. We performed a metaanalysis of randomized
      controlled trials of asymptomatic singleton gestations with previous PTB who were
      assigned randomly to prophylactic omega-3 supplementation vs control (either
      placebo or no treatment). The primary outcome was predefined as PTB at <37 weeks
      of gestation. The pooled results were reported as relative risk (RR) with 95%
      confidence interval (95% CI). The protocol of this review was registered with
      PROSPERO (registration number: CRD42015016371). Two randomized controlled trials
      that included 1080 women were analyzed. The mean gestational age at randomization
      was approximately 134 days in both groups (mean difference, 0.01 days; 95% CI, 
      0.13 to 0.14). Women who received omega-3 had similar rates of PTB at <37 weeks
      of gestation (34.5% vs 39.8%; RR, 0.81; 95% CI, 0.59-1.12) and PTB at <34 weeks
      of gestation (12.0% vs 15.4%; RR, 0.62; 95% CI, 0.26-1.46) compared with control
      subjects. The omega-3 groups had a statistically significantly longer latency
      (mean difference, 2.10 days; 95% CI, 1.98-2.22) and higher birthweight (mean
      difference, 102.52 g; 95% CI, 20.09-184.95) compared with control subjects; the
      other secondary outcomes (which included gestational age at delivery, spontaneous
      PTB at <37 and 34 weeks of gestation, admission to the intensive care unit,
      intraventricular hemorrhage, necrotizing enterocolitis, sepsis, and perinatal
      death) were similar. Omega-3 supplementation during pregnancy does not prevent
      recurrent PTB in asymptomatic singleton gestations with previous PTB. The
      benefits in longer latency and higher birth weight may deserve further study.

PMID- 25757637
TI  - The prevalence of gestational diabetes mellitus recurrence--effect of ethnicity
      and parity: a metaanalysis.
AB  - Reports on the gestational diabetes mellitus (GDM) recurrence rate have been
      highly variable. Our objectives were to examine the possible causes of GDM
      recurrence rate variability and to obtain pooled estimates in subgroups. We have
      carried out a systematic review and metaanalysis based on the Metaanalysis Of
      Observational Studies in Epidemiology statement. We identified papers published
      from 1973 to September 2014. We identified papers using Medline (PubMed and
      Ovid), ClinicalTrials.gov and Google Scholar databases, and published references.
      We included only English-language, population-based studies that reported
      specified GDM criteria and GDM recurrence rate. A total of 18 eligible studies
      with 19,053 participants were identified. We used the Cochrane's Q test of
      heterogeneity to choose the model for estimating the pooled GDM recurrence rate.
      Metaregression was also used to explore the possible causes of variability
      between studies. The pooled GDM recurrence rate was 48% (95% confidence interval,
      41-54%). A significant association between ethnicity and GDM recurrence rate was
      found (P = .02). Non-Hispanic whites had lower recurrence rate compared with
      other ethnicities (39% and 56%, respectively). Primiparous women had a lower
      recurrence rate compared with multiparous women (40% and 73%, respectively; P <
      .0001) No evidence for association between family history of diabetes and GDM
      recurrence was found. The overall GDM recurrence rate is high. Non-Hispanic
      whites and primiparous women have substantially lower GDM recurrence rates, which
      contributes to the variability between studies. Because no association between
      family history of diabetes and GDM recurrence was found, the large differences
      between ethnic groups may have also resulted from nongenetic factors. Thus,
      intervention programs could reduce the GDM recurrence rates.

PMID- 25757638
TI  - Delayed cord clamping?

PMID- 25757639
TI  - Reply: To PMID 24686151.

PMID- 25757641
TI  - Physicochemical characterization of emulgel formulated with SepineoP 600,
      SepineoSE 68 and cosolvent mixtures.
AB  - The combined properties of SepineoP 600 (S600), a self-gelling dispersion and
      SepineoSE 68 (M68), a natural liquid crystal forming surfactant, were utilized in
      the development of emulgel base for topical application. The emulgels were
      prepared in water alone or combined with propylene glycol (PG), polyethylene
      glycol 400 (PEG400) and glycerol (G) as cosolvents. Emulgels were characterized
      for their optical and flow behavior. Two model drugs: caffeine (CF) and
      methylparaben (MP) were used in the evaluation of drug permeation across the
      stratum corneum (SC). The results showed that emulgel prepared using 70% PG:water
      (1:1) and 30% S600 has the best flow behavior compared to other cosolvents. Also
      the permeability coefficient of CF was found to be higher than that of MP and the
      addition of 3% M68 improved the physical stability of the emulgel, but it did not
      affect the drug diffusion profile. 

PMID- 25757640
TI  - Tubal granuloma.

PMID- 25757642
TI  - Biophysical study on the interaction of etomidate and the carrier protein in
      vitro.
AB  - Etomidate is a unique drug used for induction of general anesthesia and sedation,
      and is usually used through intravenous injection clinically. Before targeting to
      the receptor, etomidate binds proteins in blood when it comes into veins. Thus to
      study the interaction of etomidate and serum albumin would be of great
      toxicological and pharmacological importance. In this study, the interaction
      between etomidate and human serum albumin (HSA) was studied using fluorescence
      spectroscopy, UV-vis absorption spectroscopy, Fourier transform infrared
      spectroscopy (FT-IR), circular dichroism (CD) spectroscopy, site maker
      displacement and molecular modeling methods. Investigations of the binding
      constant (K = 3.55 * 10(5 )M(-1), 295 K), the number of binding sites (n = 1.16),
      thermodynamic parameters (DeltaG = 3.13 * 10(4 )J.mol(-1), DeltaS = 364 J.mol(
      1).K(-1) and DeltaH = -6.85 * 10(5 )J.mol(-1)) for the reaction and changes to
      the binding sites and conformation in HSA in response to etomidate were
      presented. Results show that etomidate can bind HSA tightly through electrostatic
      forces, and the protein skeleton conformation and secondary structure changes
      thereby. This is the first spectroscopic report for etomidate-HSA interactions
      which illustrates the complex nature of this subject. 

PMID- 25757643
TI  - Optimization and evaluation of pluronic lecithin organogels as a transdermal
      delivery vehicle for sinomenine.
AB  - The purpose of the present study was to prepare and optimize sinomenine (SIN)
      pluronic lecithin organogels system (PLO), and to evaluate the permeability of
      the optimized PLO in vitro and in vivo. Box-Behnken design was used to optimize
      the PLO and the optimized formulation was pluronic F127 of 19.61%, lecithin of
      3.60% and SIN of 1.27%. The formulation was evaluated its skin permeation and
      drug deposition both in vitro and in vivo compared with gel. Permeation and
      deposition studies of PLO were carried out with Franz diffusion cells in vitro
      and with microdialysis in vivo. In vitro studies, permeation rate (Jss) of SIN
      from PLO was 146.55 +/- 2.93 MUg/cm(2)/h, significantly higher than that of gel
      (120.39 MUg/cm(2)/h) and the amount of SIN deposited in skin from the PLO was
      10.08 +/- 0.86 MUg/cm(2), significantly larger than that from gel (6.01 +/- 0.04
      MUg/cm(2)). In vivo skin microdialysis studies showed that the maximum
      concentration (Cmax) of SIN from PLO in "permeation study" and "drug-deposition
      study" were 150.27 +/- 20.85 MUg/ml and 67.95 MUg/ml, respectively, both
      significantly higher than that of SIN from gel (29.66 and 6.73 MUg/ml). The
      results recommend that PLO can be used as an advantageous transdermal delivery
      vehicle to enhance the permeation and skin deposition of SIN. 

PMID- 25757644
TI  - Increased dissolution rates of carbamazepine--gluconolactone binary blends
      processed by hot melt extrusion.
AB  - Carbamazepine (CBZ) shows a poor dissolution, therefore, it is important to
      enhance its dissolution in GI tract to improve its bioavailability. In the
      present study, a new hydrophilic carrier, d-gluconolactone (GNL), was extruded
      with CBZ at various molar ratios to produce granules by using hot melt extrusion
      (HME) processing. The granular extrudates were characterised by X-ray powder
      diffraction, differential scanning calorimetry and hot stage microscopy to
      determine the solid state of CBZ. It was found that bulk CBZ (Form-III)
      transformed to the polymorphic Form-I during the HME processing. GNL was proved
      to be an efficient carrier for CBZ to enhance the dissolution rate. The increase
      in the dissolution rate was observed for both physical mixtures and the
      extrudates of CBZ-GNL. However, the extrudates showed faster dissolution rates
      compared to physical mixtures in an ascending order of 2:1 < 1:1 < 1.5:1
      (CBZ:GNL). The increase in the dissolution rates was attributed to the
      transformation of CBZ III to Form-I and also to the increased drug
      wettability/solubilisation in the presence of the carrier.

PMID- 25757645
TI  - A dry powder formulation from silk fibroin microspheres as a topical auto-gelling
      device.
AB  - With the aim of establishing the formulation of a new hydrophilic auto-gelling
      medical device for biomedical applications, fibroin-based microspheres were
      prepared. The proposed microspheres were produced by a cost-effective and
      industrially scalable technique, such as the spray-drying. Spray-dried silk
      fibroin microspheres were obtained and the effects of different hydrophilic
      polymer on the process yield, microsphere morphology and conformation transition
      of fibroin were evaluated. The final auto-gelling formulations were obtained by
      adding calcium gluconate (as a calcium source for alginate crosslinking) to the
      prepared microspheres and tested by an in vitro gelling test. This study showed
      that the combination of fibroin with sodium alginate and poloxamer produced the
      most promising auto-gelling formulation for specific biomedical applications,
      such as the treatment of pressure ulcers. 

PMID- 25757646
TI  - Quaternary polymethacrylate-sodium alginate films: effect of alginate block
      structures and use for sustained release tablets.
AB  - The objectives in this study were to characterize quaternary polymethacrylate
      sodium alginate (QPM-SA) films prepared using high G block or high M block SA
      (GSA or MSA, respectively), and to investigate the effects of QPM-SA ratios, film
      coating levels and SA block structures on propranolol HCl (PPN) released from
      coated tablets. The results demonstrated that GSA and MSA shared a similar
      interaction mechanism with QPM. The QPM-GSA films had higher puncture strength
      than the QPM-MSA films in dry and wet states, whereas the % elongations were not
      different. The drug permeability of the QPM-GSA films was lower than that of the
      QPM-MSA films in both acidic and neutral media, but higher water uptake of the
      QPM-GSA films was found at neutral pH. Moreover, the QPM-MSA-coated tablets had a
      greater PPN release rate than the QPM-GSA-coated tablets, and drug release was
      dependent on the film-coating levels. In addition, the QPM-SA films at a ratio of
      4:0.5 produced a stronger film and could sustain PPN release. These results
      indicate that the QPM-GSA films had greater film strength and lower drug
      permeability than the QPM-MSA films. Additionally, the QPM-SA films have a strong
      potential for use in sustained-release tablets. 

PMID- 25757647
TI  - Different Diagnosis, Shared Vulnerabilities: The Value of Cross Disorder
      Validation of Capacity to Consent.
AB  - A screening measure of capacity to consent can provide an efficient method of
      determining the appropriateness of including individuals from vulnerable patient
      populations in research, particularly in circumstances in which no caregiver is
      available to provide surrogate consent. Seaman et al. (2015) cross-validate a
      measure of capacity to consent to research developed by Jeste et al. (2007). They
      provide data on controls, caregivers, and patients with mild cognitive impairment
      and dementia. The study demonstrates the importance of validating measures across
      disorders with different domains of incapacity, as well as the need for timely
      and appropriate follow-up with potential participants who yield positive screens.
      Ultimately clinical measures need to adapt to the dimensional diagnostic
      approaches put forward in DSM 5. Integrative models of constructs, such as
      capacity to consent, will make this process more efficient by avoiding the need
      to test measures in each disorder. Until then, cross-validation studies, such as
      the work by Seaman et al. (2015) are critical.

PMID- 25757648
TI  - Pattern of Smell Identification Impairment in Alzheimer's Disease.
AB  - Olfactory dysfunction in general, and impaired odor identification in particular,
      have been reported in Alzheimer's disease (AD). Olfactory testing may be a useful
      diagnostic aid for AD, but the types of odor most commonly affected need to be
      identified. This study aimed to determine pattern and types of odor affected in
      AD with the goal of improving clinical applicability. 54 outpatients with mild to
      moderate AD and 40 age and gender-matched non-demented controls (NDC) were tested
      using British version of University of Pennsylvania Smell Identification Test
      (UPSIT; Sensonics, Inc., Haddon Heights, NJ) and data analyzed to identify an
      optimal subset of UPSIT to best differentiate AD patients from controls. AD
      subjects had significantly lower UPSIT total scores than NDC. Random Forest with
      backward elimination identified 12 UPSIT items which accurately differentiated AD
      patients compared to controls (sensitivity, 0.89 and specificity, 0.83, positive
      predictive value of 0.889, and negative predictive value of 0.833). The 12 smell
      items found to be most affected in AD subjects reflects important attributes such
      as safety and food, known to be affected in people with AD and that has the
      potential to impair activities of daily living. The 12 items of British UPSIT
      most affected in AD subjects provides a potential brief scale for early detection
      of AD in clinical settings. Independent replication is needed to validate these
      findings. 

PMID- 25757649
TI  - Raul Mena: 1953-2014.

PMID- 25757650
TI  - Role of the Visual and Auditory Systems in Postural Stability in Alzheimer's
      Disease.
AB  - BACKGROUND: Postural stability requires the integration of multisensory input
      information and translation into appropriate motor responses. Surprisingly, few
      previous studies have addressed the role of auditory input on postural stability
      in healthy subjects, and none has investigated this in Alzheimer's disease (AD).
      OBJECTIVE: To assess the influence of the visual and auditory systems on postural
      stability in patients with AD and healthy subjects. METHODS: Twenty-four patients
      with AD and healthy age-matched subjects were examined by kinematic postural
      analysis (inertia measurement units placed at the center of mass of the body)
      under four different conditions: stance with eyes open and eyes closed, with and
      without suppression of background noise (using ear defenders). The effects of
      visual and auditory influences were analyzed independently and in conjunction.
      RESULTS: In both groups, visual suppression had a negative impact on postural
      stability, while suppression of background noise, non-specifically and without
      spatial cues, significantly benefited postural stability. We also observed that
      in both groups, the positive effect of background noise suppression was
      insufficient to compensate for the negative effect of visual suppression, to
      which the patients were significantly more vulnerable. CONCLUSIONS: Audition,
      albeit less significant than vision, also plays a role in the multi-sensorial
      dynamic control of postural stability by the central nervous system. In everyday
      life, audition is likely to be a relevant factor in postural stability. This is
      especially relevant in AD in which, even when the peripheral sensory system is
      intact, the central processing is impaired and sensory dependence is re-weighted.

PMID- 25757651
TI  - Understanding Emotions in Frontotemporal Dementia: The Explicit and Implicit
      Emotional Cue Mismatch.
AB  - BACKGROUND: Previous studies have reported significant deficits in emotion
      recognition among individuals along the frontotemporal dementia (FTD) spectrum.
      The basis of emotional impairment is still poorly understood and explicit
      (emotion appraisal) and implicit (autonomic system activity) responses have not
      been carefully evaluated. OBJECTIVE: We investigated explicit evaluation of
      emotions by testing valence and arousal using self-report measures and we also
      assessed automatic responses to emotional cues, using autonomic measures (skin
      conductance response and heart rate). METHODS: 16 behavioral variant FTD and 12
      agrammatic variants of primary progressive aphasia patients were included. The
      performance of these patients was compared to a group of 14 patients with
      Alzheimer's disease and 20 healthy controls. Each subject was required to observe
      and evaluate affective pictures while autonomic parameters were recorded.
      RESULTS: FTD patients preserved a functional general competency in terms of
      valence (correct positive versus negative attribution) and arousal (correct
      dichotomy between high versus low arousal category) distinction. These patients
      showed significant changes in autonomic implicit response compared to the other
      groups. The mismatch between explicit and implicit responsiveness to emotional
      cues was found both in behavioral variant FTD and in agrammatic variants of
      primary progressive aphasia. Emotional responsiveness was related to the severity
      of behavioral abnormalities as measured by the Frontal Behavioral Inventory and
      associated with atrophy of the left putamen. CONCLUSION: The present findings
      indicate that FTD patients are able to explicitly "appraise" the emotion, but
      they cannot implicitly "feel" the emotion. This mismatch between the two levels
      may help explain the general emotional behavior impairment found in these
      patients.

PMID- 25757652
TI  - Modulation of hippocampal theta and hippocampal-prefrontal cortex function by a
      schizophrenia risk gene.
AB  - Hippocampal theta-band oscillations are thought to facilitate the co-ordination
      of brain activity across distributed networks, including between the hippocampus
      and prefrontal cortex (PFC). Impairments in hippocampus-PFC functional
      connectivity are implicated in schizophrenia and are associated with a
      polymorphism within the ZNF804A gene that shows a genome-wide significant
      association with schizophrenia. However, the mechanisms by which ZNF804A affects
      hippocampus-PFC connectivity are unknown. We used a multimodal imaging approach
      to investigate the impact of the ZNF804A polymorphism on hippocampal theta and
      hippocampal network coactivity. Healthy volunteers homozygous for the ZNF804A
      rs1344706 (A[risk]/C[nonrisk]) polymorphism were imaged at rest using both
      magnetoencephalography (MEG) and functional magnetic resonance imaging (fMRI). A
      dual-regression approach was used to investigate coactivations between the
      hippocampal network and other brain regions for both modalities, focusing on the
      theta band in the case of MEG. We found a significant decrease in
      intrahippocampal theta (using MEG) and greater coactivation of the superior
      frontal gyrus with the hippocampal network (using fMRI) in risk versus nonrisk
      homozygotes. Furthermore, these measures showed a significant negative
      correlation. Our demonstration of an inverse relationship between hippocampal
      theta and hippocampus-PFC coactivation supports a role for hippocampal theta in
      coordinating hippocampal-prefrontal activity. The ZNF804A-related differences
      that we find in hippocampus-PFC coactivation are consistent with previously
      reported associations with functional connectivity and with these changes lying
      downstream of altered hippocampal theta. Changes in hippocampal-PFC co
      ordination, driven by differences in oscillatory activity, may be one mechanism
      by which ZNF804A impacts on brain function and risk for psychosis.

PMID- 25757653
TI  - Surveillance of cardiovascular diseases using a multivariate dynamic screening
      system.
AB  - In the SHARe Framingham Heart Study of the National Heart, Lung and Blood
      Institute, one major task is to monitor several health variables (e.g., blood
      pressure and cholesterol level) so that their irregular longitudinal pattern can
      be detected as soon as possible and some medical treatments applied in a timely
      manner to avoid some deadly cardiovascular diseases (e.g., stroke). To handle
      this kind of applications effectively, we propose a new statistical methodology
      called multivariate dynamic screening system (MDySS) in this paper. The MDySS
      method combines the major strengths of the multivariate longitudinal data
      analysis and the multivariate statistical process control, and it makes decisions
      about the longitudinal pattern of a subject by comparing it with other subjects
      cross sectionally and by sequentially monitoring it as well. Numerical studies
      show that MDySS works well in practice.

PMID- 25757655
TI  - High-yield nanosized (Si)AlPO-41 using ethanol polarity equalization and co
      templating synthesis approach.
AB  - Control of the crystallite dimensions of the microporous aluminophosphate AlPO-41
      (AFO-type framework structure), and the Si-containing analogue SAPO-41, was
      attained down to the nanometer scale under stable hydrothermal conditions. The
      combined application of a tetraalkylammonium co-template (tetrapentylammonium
      hydroxide) along with an amine structure directing agent (n-dipropylamine)
      stabilized through the use of ethanol in the initial suspension enables a
      crystallization medium, which remains homogeneous throughout the entire
      synthesis. As a direct consequence of the optimized homogeneity of the
      suspension, the AFO-type microporous nanocrystals (AlPO-41 and SAPO-41) with a
      size in the range of 30-500 nm with yields surpassing 50% are obtained. The
      feasibility to obtain nanosized AlPO-41 and SAPO-41 crystals using ethanol as a
      polarity equalizing agent, resulting in a scalable hydrothermal synthesis from
      non-colloidal starting mixtures without the use of other assisting methods, is
      presented. 

PMID- 25757654
TI  - Long-term cognitive follow-up of Parkinson's disease patients with impulse
      control disorders.
AB  - This study investigated cognitive functions in Parkinson's disease (PD) patients
      with impulse control disorders (ICDs) and aimed to identify possible predictors
      of behavioral outcome. In this longitudinal cohort study, 40 PD outpatients with
      ICDs and 40 without, were matched for sex, age at PD onset, age and disease
      duration at cognitive assessment. All patients had two neuropsychological
      assessments at least 2 years apart (mean, 3.5 years). Multivariate logistic
      regression analysis was performed to identify predictors of ICDs remission at
      follow-up. The PD patients with and without ICDs had overall comparable cognitive
      performance at baseline. When evaluating changes between baseline and follow-up,
      we found significant group * time interactions in several frontal lobe-related
      tests, with the ICDs group showing a less pronounced worsening over time. ICDs
      remission was associated with better performance at baseline in working memory
      related tasks, such as digit span (odds ratio [OR] = 2.69 [95% confidence
      interval (CI), 1.09-6.66]) and attentive matrices (OR=1.19 [95%CI, 1.03-1.37]).
      ICDs remitters and non-remitters had no remarkable differences in baseline PD
      related features and therapy management strategies (including the extent of
      dopamine agonist dose reduction). In conclusion, ICDs in PD patients are not
      related to greater cognitive impairment or executive dysfunction, but rather show
      relatively lower cognitive decline over time. The impaired top-down inhibitory
      control characterizing ICDs is likely attributable to a drug-induced
      overstimulation of relatively preserved prefrontal cognitive functions. Full
      behavioral remission in the long term was predicted by better working memory
      abilities. (c) 2015 International Parkinson and Movement Disorder Society. 

PMID- 25757656
TI  - From experimental zoology to big data: Observation and integration in the study
      of animal development.
AB  - The founding of the Journal of Experimental Zoology in 1904 was inspired by a
      widespread turn toward experimental biology in the 19th century. The founding
      editors sought to promote experimental, laboratory-based approaches, particularly
      in developmental biology. This agenda raised key practical and epistemological
      questions about how and where to study development: Does the environment matter?
      How do we know that a cell or embryo isolated to facilitate observation reveals
      normal developmental processes? How can we integrate descriptive and experimental
      data? R.G. Harrison, the journal's first editor, grappled with these questions in
      justifying his use of cell culture to study neural patterning. Others confronted
      them in different contexts: for example, F.B. Sumner insisted on the primacy of
      fieldwork in his studies on adaptation, but also performed breeding experiments
      using wild-collected animals. The work of Harrison, Sumner, and other early
      contributors exemplified both the power of new techniques, and the meticulous
      explanation of practice and epistemology that was marshaled to promote
      experimental approaches. A century later, experimentation is widely viewed as the
      standard way to study development; yet at the same time, cutting-edge "big data"
      projects are essentially descriptive, closer to natural history than to the
      approaches championed by Harrison et al. Thus, the original questions about how
      and where we can best learn about development are still with us. Examining their
      history can inform current efforts to incorporate data from experiment and
      description, lab and field, and a broad range of organisms and disciplines, into
      an integrated understanding of animal development.

PMID- 25757657
TI  - Pharmacodynamic effects of C-domain-specific ACE inhibitors on the renin
      angiotensin system in myocardial infarcted rats.
AB  - INTRODUCTION: The renin-angiotensin system (RAS) is a dynamic network that plays
      a critical role in blood pressure regulation and fluid and electrolyte
      homeostasis. Modulators of the RAS, such as angiotensin-converting enzyme (ACE)
      inhibitors, are widely used to treat hypertension, heart failure and myocardial
      infarction. METHODS: The effect of ACE inhibitors (lisinopril and C-domain
      selective LisW-S) on the constituent peptides of the RAS following myocardial
      infarction was examined in rats. Ten angiotensin peptides were analysed using a
      sensitive LC-MS/MS-based assay to examine both the circulating and equilibrium
      levels of these peptides. RESULTS: Administration of lisinopril or LisW-S caused
      a significant decrease in Ang 1-8/Ang 1-10 ratios as determined by circulating
      and equilibrium peptide level analysis. Furthermore, Ang 1-7 levels were elevated
      by both ACE inhibitors, but only lisinopril decreased the Ang 1-5/Ang 1-7 ratio.
      This indicates LisW-S C-domain specificity as Ang 1-5 is generated by hydrolysis
      of Ang 1-7 by the N-domain. Further corroboration of LisW-S C-domain specificity
      is that only lisinopril increased the circulating levels of the N-domain ACE
      substrate Ac-SDKP. CONCLUSION: LisW-S is able to effectively block ACE in vivo by
      C-domain-selective inhibition. The LC-MS/MS-based assay allows the evaluation of
      the pharmacologic impact of RAS inhibitors in different pathophysiological
      conditions.

PMID- 25757658
TI  - Angiotensin II type 2 receptor signaling affects dopamine levels in the brain and
      prevents binge eating disorder.
AB  - INTRODUCTION: Binge eating disorder (BED) is associated with dopaminergic
      activation as food reward, resulting in metabolism-related disorders. Stimulation
      of angiotensin type 2 (AT2) receptor is reported to inhibit dopamine synthesis.
      We investigated the possible roles of AT2 receptor-mediated dopamine regulation
      in the pathogenesis of BED. MATERIALS AND METHODS: Male C57BL/6 mice, type 2
      diabetic (KKAy) mice and AT2 receptor-null (AT2KO) mice at eight weeks old were
      treated with AT2 receptor agonist, compound 21 (C21) or saline for two weeks.
      Mice were subjected to fasting for two days followed by re-feeding for seven
      days. RESULTS: Treatment with C21 attenuated the rebound proportion of body
      weight, food intake and water intake in KKAy mice, but not in C57BL/6 and AT2KO
      mice. Dopamine concentration in the striatum was further increased by fasting in
      KKAy and AT2KO mice. Administration of C21 significantly attenuated this fasting
      induced increase in dopamine level only in KKAy mice. Dopamine receptor D1, D2
      expression in the substantia nigra were markedly lower in KKAy mice compared with
      C57BL/6 mice, while administration of C21 increased their expression in KKAy
      mice. CONCLUSIONS: Our study suggests that AT2 receptor stimulation may be a new
      therapeutic approach to improve eating disorder associated with dopamine
      resistance.

PMID- 25757659
TI  - Isolation, characterization and investigation of differentiation potential of
      human periodontal ligament cells and dental follicle progenitor cells and their
      response to BMP-7 in vitro.
AB  - The aim of this study was to assess the factors, mechanisms and the differences
      between periodontal ligament (PDL) cells and denta l follicle (DF) progenitor
      cells towards the osteoblastic/cementoblastic differentiation and to investigate
      the effects of BMP-7 on developmental (DF) and mature tissue-derived (PDL) cells,
      respectively. Primary cell culture of PDL cells and DF progenitor cells was
      performed. Osteogenic differentiation was evaluated using von Kossa, Alizarin Red
      S and immuno-histo-chemistry staining of osteocalcin. Gene expression pattern was
      evaluated via real-time PCR. A series of CD surface marks were tested using flow
      cytometry and fluorescence-activated cell-sorting analysis was performed. Real
      time RT-PCR demonstrated similar gene expression pattern of PDL cells and DF
      progenitor cells: the expression of OPN and OCN significantly was elevated when
      incubated with osteogenic components, Runx2 was unaffected, and Osteorix was
      hardly expressed whether in basic medium or induction medium. In addition, BMP-7
      induced osteoblast/cementoblast differentiation of PDLSCs and DF progenitor cells
      in a dose- and time-dependent manner, as reflected by enhanced Runx2 and (OCN)
      mRNA transcript expression. BMP-7 triggers PDL cells and DF progenitor cells to
      differentiate towards an osteoblast/cementoblast phenotype.

PMID- 25757660
TI  - The interaction between the spatial distribution of resource patches and
      population density: consequences for intraspecific growth and morphology.
AB  - How individuals within a population distribute themselves across resource patches
      of varying quality has been an important focus of ecological theory. The ideal
      free distribution predicts equal fitness amongst individuals in a 1 : 1 ratio
      with resources, whereas resource defence theory predicts different degrees of
      monopolization (fitness variance) as a function of temporal and spatial resource
      clumping and population density. One overlooked landscape characteristic is the
      spatial distribution of resource patches, altering the equitability of resource
      accessibility and thereby the effective number of competitors. While much work
      has investigated the influence of morphology on competitive ability for different
      resource types, less is known regarding the phenotypic characteristics conferring
      relative ability for a single resource type, particularly when exploitative
      competition predominates. Here we used young-of-the-year rainbow trout
      (Oncorhynchus mykiss) to test whether and how the spatial distribution of
      resource patches and population density interact to influence the level and
      variance of individual growth, as well as if functional morphology relates to
      competitive ability. Feeding trials were conducted within stream channels under
      three spatial distributions of nine resource patches (distributed, semi-clumped
      and clumped) at two density levels (9 and 27 individuals). Average trial growth
      was greater in high-density treatments with no effect of resource distribution.
      Within-trial growth variance had opposite patterns across resource distributions.
      Here, variance decreased at low-population, but increased at high-population
      densities as patches became increasingly clumped as the result of changes in the
      levels of interference vs. exploitative competition. Within-trial growth was
      related to both pre- and post-trial morphology where competitive individuals were
      those with traits associated with swimming capacity and efficiency: larger
      heads/bodies/caudal fins and less angled pectoral fins. The different degrees of
      within-population growth variance at the same density level found here, as a
      function of spatial resource distribution, provide an explanation for the
      inconsistencies in within-site growth variance and population regulation often
      noted with regard to density dependence in natural landscapes. 

PMID- 25757661
TI  - Alogliptin, a dipeptidyl peptidase-4 inhibitor, regulates the atrial
      arrhythmogenic substrate in rabbits.
AB  - BACKGROUND: Dipeptidyl peptidase-4 (DPP-4) inhibitors were recently reported to
      have cardioprotective effects via amelioration of ventricular function. However,
      the role of DPP-4 inhibition in atrial remodeling, especially of the
      arrhythmogenic substrate, remains unclear. OBJECTIVE: We investigated the effects
      of a DPP-4 inhibitor, alogliptin, on atrial fibrillation (AF) in a rabbit model
      of heart failure caused by ventricular tachypacing (VTP). METHODS: Rabbits
      subjected to VTP at 380 bpm for 1 or 3 weeks, with or without alogliptin
      treatment, were assessed using echocardiography, electrophysiology, histology,
      and immunoblotting and compared with nonpaced animals. RESULTS: VTP rabbits
      exhibited increased duration of atrial burst pacing-induced AF, whereas
      administration of alogliptin shortened this duration by 73%. The extent of atrial
      fibrosis after VTP was reduced by 39% in the alogliptin-treated group. VTP
      rabbits treated with alogliptin displayed a 1.6-fold increase in left atrial
      myocardial capillary density compared with nontreated rabbits. A 2-fold increase
      in endothelial nitric oxide synthase (eNOS) phosphorylation was observed in the
      left atrium of alogliptin-treated rabbits compared with nontreated rabbits.
      Moreover, a nitric oxide synthase inhibitor (N(omega)-nitro-l-arginine methyl
      ester) blocked the beneficial effects of alogliptin on AF duration, fibrosis, and
      capillary density. CONCLUSION: Alogliptin shortened the duration of AF caused by
      VTP-induced fibrotic atrial tissue by augmenting atrial angiogenesis and
      activating eNOS. Our findings suggest that DPP-4 inhibitors may be useful in the
      prevention of heart failure-induced AF.

PMID- 25757662
TI  - The role of the sodium current complex in a nonreferred nationwide cohort of
      sudden infant death syndrome.
AB  - BACKGROUND: Sudden infant death syndrome (SIDS) is the most common cause of death
      in infants between the age of 1 month and 1 year. Rare variants in Nav1.5 encoded
      by SCN5A are known to play a role in SIDS; however, the combined role of the
      sodium current complex is unknown. OBJECTIVE: The purpose of this study was to
      investigate the role of the sodium current complex in a nonreferred nationwide
      cohort of SIDS cases. METHODS: DNA was extracted from dried blood spot samples
      from the Danish Neonatal Screening Biobank. In total, 66 non-referred SIDS cases
      born in Denmark in the period of 2000-2006 were screened for genetic variants in
      the 8 major genes involved in the regulation of the Nav1.5 channel complex:
      SCN5A, SCN1B, SCN2B, SCN3B, SCN4B, GPD1L, SNTA1, and CAV3. Patch-clamp analyses
      were performed on variants not previously characterized. RESULTS: In total, 8
      patients (12%) had nonsynonymous rare variants in the sodium current genes. SCN5A
      harbored 6 rare variants (R458C, R535*, S1103Y, R1193Q, S1609L, and Q1909R);
      CAV3, 1 rare variant (T78M); GPD1L, 1 rare variant (R220H); and SCN3B, 1 rare
      variant (L10P). Four variants were considered likely pathogenic and 5 variants of
      unknown significance. SCN5A R1193Q and GPD1L R220H (both considered variants of
      unknown significance) were present in the same infant. Functional analysis of
      variants not previously characterized (R458C, S1609L, and Q1909R in SCN5A)
      predominantly revealed increased transient and sustained sodium current.
      CONCLUSION: In a nonreferred nationwide Danish cohort of SIDS cases, up to 5/66
      (7.5%) of SIDS cases can be explained by genetic variants in the sodium channel
      complex genes.

PMID- 25757663
TI  - Viscoelasticity using reactive constrained solid mixtures.
AB  - This study presents a framework for viscoelasticity where the free energy density
      depends on the stored energy of intact strong and weak bonds, where weak bonds
      break and reform in response to loading. The stress is evaluated by
      differentiating the free energy density with respect to the deformation gradient,
      similar to the conventional approach for hyperelasticity. The breaking and
      reformation of weak bonds is treated as a reaction governed by the axiom of mass
      balance, where the constitutive relation for the mass supply governs the bond
      kinetics. The evolving mass contents of these weak bonds serve as observable
      state variables. Weak bonds reform in an energy-free and stress-free state,
      therefore their reference configuration is given by the current configuration at
      the time of their reformation. A principal advantage of this formulation is the
      availability of a strain energy density function that depends only on observable
      state variables, also allowing for a separation of the contributions of strong
      and weak bonds. The Clausius-Duhem inequality is satisfied by requiring that the
      net free energy from all breaking bonds must be decreasing at all times. In the
      limit of infinitesimal strains, linear stress-strain responses and first-order
      kinetics for breaking and reforming of weak bonds, the reactive framework reduces
      exactly to classical linear viscoelasticity. For large strains, the reactive and
      classical quasilinear viscoelasticity theories produce different equations,
      though responses to standard loading configurations behave similarly. This
      formulation complements existing tools for modeling the nonlinear viscoelastic
      response of biological soft tissues under large deformations. 

PMID- 25757665
TI  - Study on the influence of the fetus head molding on the biomechanical behavior of
      the pelvic floor muscles, during vaginal delivery.
AB  - Pelvic floor injuries during vaginal delivery are considered a significant risk
      factor to develop pelvic floor dysfunction. The molding of the fetus head during
      vaginal delivery facilitates the labor progress, since it adjusts to the birth
      canal geometry. In this work, a finite element model was used to represent the
      effects induced by the passage of the fetus head on the pelvic floor. The
      numerical model used for this simulation included the pelvic floor muscles
      attached to the bones, and a fetus body. The model of the fetus head included the
      skin and soft tissues, the skull with sutures and fontanelles, and the brain. The
      fetus head movements during birth in vertex position were simulated: descent,
      internal rotation and extension. Two models of the fetus head were compared: a
      rigid and a deformable one, with the inclusion of the cranial sutures. The
      influence of the fetus head molding on the pelvic floor muscles was analyzed by
      evaluating their reaction forces, stretch, and stress and strain fields.
      Additionally, anatomical indices for the molding of the fetal skull were obtained
      and compared with clinical data. The passage of the deformable fetus head through
      the birth canal leads to a reduction of 17.3% on the reaction forces on the
      pelvic floor muscles when compared to the ones of a rigid head. Furthermore, the
      fetus head molding implies inferior resistance to rotation resulting in a
      reduction of 1.86% in muscle stretching. Quantitative evaluation of the fetus
      head molding showed good agreement with clinical experiments.

PMID- 25757664
TI  - A multi-compartment 3-D finite element model of rectocele and its interaction
      with cystocele.
AB  - We developed a subject-specific 3-D finite element model to understand the
      mechanics underlying formation of female pelvic organ prolapse, specifically a
      rectocele and its interaction with a cystocele. The model was created from MRI 3
      D geometry of a healthy 45 year-old multiparous woman. It included anterior and
      posterior vaginal walls, levator ani muscle, cardinal and uterosacral ligaments,
      anterior and posterior arcus tendineus fascia pelvis, arcus tendineus levator
      ani, perineal body, perineal membrane and anal sphincter. Material properties
      were mostly from the literature. Tissue impairment was modeled as decreased
      tissue stiffness based on previous clinical studies. Model equations were solved
      using Abaqus v 6.11. The sensitivity of anterior and posterior vaginal wall
      geometry was calculated for different combinations tissue impairments under
      increasing intraabdominal pressure. Prolapse size was reported as pelvic organ
      prolapse quantification system (POP-Q) point at point Bp for rectocele and point
      Ba for cystocele. Results show that a rectocele resulted from impairments of the
      levator ani and posterior compartment support. For 20% levator and 85% posterior
      support impairments, simulated rectocele size (at POP-Q point: Bp) increased 0.29
      mm/cm H2O without apical impairment and 0.36 mm/cm H2O with 60% apical
      impairment, as intraabdominal pressures increased from 0 to 150 cm H2O. Apical
      support impairment could result in the development of either a cystocele or
      rectocele. Simulated repair of posterior compartment support decreased rectocele
      but increased a preexisting cystocele. We conclude that development of rectocele
      and cystocele depend on the presence of anterior, posterior, levator and/or or
      apical support impairments, as well as the interaction of the prolapse with the
      opposing compartment.

PMID- 25757667
TI  - Re-evaluation of the amplitude-force relationship of trunk muscles.
AB  - Amplitude-force relationships of major trunk muscles are established in terms of
      curve characteristics, but up to now were not normalized with respect to maximum
      voluntary contraction (MVC) force levels. The study therefore aims at a re
      evaluation of trunk muscle amplitude-force relationship data according to MVC.
      Surface EMG of five major trunk muscles was taken from 50 healthy subjects of
      both sexes (age 20-40 years). All tasks were performed in a device where
      submaximal loads on the trunk were applied by gradually tilting the subjects in
      sagittal plane to horizontal position. MVC flexion and extension forces were
      determined in upright position using an additional harness over the subject's
      shoulders. Furthermore, the subject's upper body mass (UBM) was obtained during
      forward tilt to horizontal. MVC to UBM ratio was calculated, corrected by the
      actual tilt angle, and these linearly estimated values compared with the measured
      relative values according to MVC. All abdominal muscles confirmed the known non
      linear amplitude-force relationship. At low load levels the linearly estimated
      values overestimated the measured ones and, at higher load levels, underestimated
      the true stress levels considerably. Back muscles confirmed the known linear
      curve shape, but for the longissimus muscle at L1 level measured data was always
      below estimated values. With increasing load, muscular stress of abdominal
      muscles changes from overestimated towards considerably underestimated values if
      expected stress levels are based on linear interpolation. Major back muscles'
      activation levels are nearly linear, but the amplitude-force relationship values
      seem overestimated for longissimus.

PMID- 25757666
TI  - A statistically-augmented computational platform for evaluating meniscal
      function.
AB  - Meniscal implants have been developed in an attempt to provide pain relief and
      prevent pathological degeneration of articular cartilage. However, as yet there
      has been no systematic and comprehensive analysis of the effects of the meniscal
      design variables on meniscal function across a wide patient population, and there
      are no clear design criteria to ensure the functional performance of candidate
      meniscal implants. Our aim was to develop a statistically-augmented,
      experimentally-validated, computational platform to assess the effect of meniscal
      properties and patient variables on knee joint contact mechanics during the
      activity of walking. Our analysis used Finite Element Models (FEMs) that
      represented the geometry, kinematics as based on simulated gait and contact
      mechanics of three laboratory tested human cadaveric knees. The FEMs were
      subsequently programmed to represent prescribed meniscal variables
      (circumferential and radial/axial moduli-Ecm, Erm, stiffness of the meniscal
      attachments-Slpma, Slamp) and patient variables (varus/valgus alignment-VVA, and
      articular cartilage modulus-Ec). The contact mechanics data generated from the
      FEM runs were used as training data to a statistical interpolator which estimated
      joint contact data for untested configurations of input variables. Our data
      suggested that while Ecm and Erm of a meniscus are critical in determining knee
      joint mechanics in early and late stance (peak 1 and peak 3 of the gait cycle),
      for some knees that have greater laxity in the mid-stance phase of gait, the
      stiffness of the articular cartilage, Ec, can influence force distribution across
      the tibial plateau. We found that the medial meniscus plays a dominant load
      carrying role in the early stance phase and less so in late stance, while the
      lateral meniscus distributes load throughout gait. Joint contact mechanics in the
      medial compartment are more sensitive to Ecm than those in the lateral
      compartment. Finally, throughout stance, varus-valgus alignment can overwhelm
      these relationships while the stiffness of meniscal attachments in the range
      studied have minimal effects on the knee joint mechanics. In summary, our
      statistically-augmented, computational platform allowed us to study how meniscal
      implant design variables (which can be controlled at the time of manufacture or
      implantation) interact with patient variables (which can be set in FEMs but
      cannot be controlled in patient studies) to affect joint contact mechanics during
      the activity of simulated walking. 

PMID- 25757668
TI  - Decreased expression of ARID1A contributes to infiltrative growth of esophageal
      squamous cell carcinoma.
AB  - The clinical outcome for esophageal squamous cell carcinoma (ESCC) patients is
      often poor because of the invasive nature of this tumor type. AT-rich interactive
      domain 1A (ARID1A) functions as a tumor suppressor, and its gene mutation has
      been reported in various human malignancies. ARID1A is a non-catalytic subunit of
      the SWItch/Sucrose Non Fermentable (SWI/SNF) chromatin-remodeling complex that
      regulates gene transcription. Decreased expression of ARID1A protein has been
      reported to decrease the expression of E-cadherin, an adhesion protein. However,
      the correlation between ARID1A and E-cadherin expression status in ESCC remains
      largely unknown. To address this issue, we examined the expression of ARID1A and
      E-cadherin in tumor specimens excised from 83 ESCC patients using
      immunohistochemical analysis. The intensity of the ARID1A immunoreactivity was
      significantly lower in tumors with a growth pattern characterized by ill-defined
      borders than that in tumors with an expansive growth pattern having a well
      demarcated border or tumors with an intermediate growth pattern. Thus, decreased
      ARID1A immunoreactivity correlated with infiltrative growth of ESCC. In contrast,
      E-cadherin status did not correlate with the infiltrative growth pattern of ESCC.
      Moreover, ARID1A expression status did not significantly correlate with any of
      other clinicopathological factors, E-cadherin expression levels, or the clinical
      outcome of the patients. On the other hand, the patients with tumors expressing
      low levels of E-cadherin exhibited significantly lower survival rates than those
      with high expression. In conclusion, reduced ARID1A expression in tumor tissues
      contributes to infiltrative growth of ESCC, irrespective of E-cadherin expression
      levels. 

PMID- 25757670
TI  - Social media in adolescent health literacy education: a pilot study.
AB  - BACKGROUND: While health literacy has gained notice on a global stage, the
      initial focus on seeking associations with medical conditions may have overlooked
      its impact across generations. Adolescent health literacy, specifically in
      dentistry, is an underexplored area despite the significance of this formative
      stage on an individual's approach to healthy lifestyles and behaviors. OBJECTIVE:
      The aim is to conduct a pilot study to evaluate the efficacy of three major
      social media outlets - Twitter, Facebook, and YouTube - in supporting
      adolescents' oral health literacy (OHL) education. METHODS: A random sample of 22
      adolescents (aged 14-16 years) from an English-medium international school in
      Hong Kong provided informed consent. Sociodemographic information, including
      English language background, social media usage, and dental experience were
      collected via a questionnaire. A pre- and post-test of OHL (REALD-30) was
      administered by two trained, calibrated examiners. Following pre-test,
      participants were randomly assigned to one of three social media outlets:
      Twitter, Facebook, or YouTube. Participants received alerts posted daily for 5
      consecutive days requiring online accessing of modified and original OHL
      education materials. One-way ANOVA ( analysis of variance) was used to compare
      the mean difference between the pre- and the post-test results among the three
      social media. RESULTS: No associations were found between the social media
      allocated and participants' sociodemographics, including English language
      background, social media usage, and dental experience. Of the three social media,
      significant differences in literacy assessment scores were evident for
      participants who received oral health education messages via Facebook (P=.02) and
      YouTube (P=.005). CONCLUSIONS: Based on the results of the pilot study, Facebook
      and YouTube may be more efficient media outlets for OHL promotion and education
      among adolescent school children when compared to Twitter. Further analyses with
      a larger study group is warranted.

PMID- 25757671
TI  - Behind the monitor--the trouble with telemetry: a teachable moment.

PMID- 25757669
TI  - Tim-3 protects decidual stromal cells from toll-like receptor-mediated apoptosis
      and inflammatory reactions and promotes Th2 bias at the maternal-fetal interface.
AB  - Toll-like receptors (TLRs) are important in mediating immune responses against
      various pathogens during pregnancy. However, uncontrolled TLR-triggered
      inflammation will endanger normal pregnancy, resulting in pregnancy loss.
      Therefore, maintenance of a moderate inflammatory response is crucial for
      successful pregnancy under conditions of infection. Here, we demonstrated
      significantly lowered expression of T-cell immunoglobulin and mucin domain 3 (Tim
      3) in miscarried decidual stromal cells (DSCs), indicating that Tim-3 might play
      important roles in maintaining successful pregnancies. Activation of TLR
      signaling induced pro-inflammatory cytokine production and apoptosis of DSCs,
      which was accompanied by up-regulated Tim-3 expression. Tim-3, in turn, protected
      DSCs from TLR-mediated apoptosis in an ERK1/2 pathway-dependent manner. In
      addition, Tim-3 inhibited TLR signaling-induced inflammatory cytokine production
      by DSCs through suppressing NF-kappaB activation. Tim-3 increased production of T
      helper 2 (Th2)-type cytokines by DSCs and reversed the inhibitory effect of LPS
      on Th2 cytokine generation by up-regulation of interferon regulatory factor 4
      expression. Tim-3 blockade abolished the effect of Tim-3 on the inflammatory
      response to LPS stimulation. Thus, Tim-3 signaling could represent a "self
      control" mechanism in TLR-triggered inflammation during pregnancy. These findings
      identify Tim-3 as a key regulator of DSCs and suggest its potential as a target
      for the treatment of spontaneous abortion. 

PMID- 25757672
TI  - The effects of nicotine dependence and acute abstinence on the processing of drug
      and non-drug rewards.
AB  - RATIONALE: Drug addiction may be characterised by a hypersensitivity to drug
      rewards and a hyposensitivity to non-drug rewards. This imbalance may become
      further polarised during acute abstinence. OBJECTIVES: (i) Examine the
      differences between dependent and occasional smokers in choices for, motivation
      for and self-reported wanting and liking of cigarette and non-drug rewards. (ii)
      Examine the effects of 12-h nicotine abstinence on these metrics. METHODS:
      Dependent (n = 20) and occasional, non-dependent smokers (n = 20) were tested
      after ad libitum smoking and >=12-h of nicotine abstinence. A novel task was
      developed (Drug, Reward and Motivation-Choice (DReaM-Choice)) in which different
      rewards (cigarettes, music and chocolate) could be won. In each trial,
      participants chose between two rewards and then could earn the chosen reward via
      repeated button-pressing. Participants subsequently 'consumed' and rated
      subjective liking of the rewards they had won. RESULTS: Compared with occasional
      smokers, dependent smokers made more choices for (p < 0.001), pressed more for (p
      = 0.046) and reported more wanting (p = 0.007) and liking (p < 0.001) of
      cigarettes, and also made fewer choices for chocolate (p = 0.005). There were no
      differences between the groups on button-pressing for chocolate or music.
      However, the balance between drug and non-drug reward processing was different
      between the groups across all metrics. Twelve-hour nicotine abstinence led to
      more cigarette choices (p < 0.001) and fewer music choices (p = 0.042) in both
      groups. CONCLUSIONS: Nicotine dependence was associated with a hypersensitivity
      to cigarette rewards, but we found little evidence indicating a hyposensitivity
      to non-drug rewards. Our findings question the moderating influence of dependence
      on how acute nicotine abstinence affects reward processing.

PMID- 25757673
TI  - Effect of extended-release naltrexone on striatal dopamine transporter
      availability, depression and anhedonia in heroin-dependent patients.
AB  - RATIONALE: Extended-release naltrexone (XRNT), an opioid receptor antagonist, is
      successfully used in the treatment of opioid dependence. However, naltrexone
      treatment of opioid-dependent patients may reduce striatal dopamine transporter
      (DAT) availability and cause depression and anhedonia. OBJECTIVES: The aim of
      this study is to investigate changes in striatal DAT availability and symptoms of
      depression (Beck Depression Inventory (BDI)) and anhedonia (Snaith Hamilton
      Pleasure Scale (SHAPS)) before and during XRNT treatment. METHODS: At baseline,
      ten detoxified heroin-dependent patients and 11 matched healthy controls
      underwent [(123)I]FP-CIT single photon emission computed tomography (SPECT)
      imaging to assess striatal DAT binding. Patients underwent a second SPECT scan 2
      weeks after an intramuscular injection with XRNT. RESULTS: At baseline, the mean
      binding potential (BPND) in the putamen was at a trend level lower and the mean
      BDI score was significantly higher in heroin patients (n = 10) than in controls
      (n = 11) (3.45 +/- 0.88 vs. 3.80 +/- 0.61, p = 0.067, d = -0.48 and 12.75 +/-
      7.40 vs. 5.20 +/- 4.83, p = 0.019, d = 1.24, respectively). Post hoc analyses in
      subgroups with negative urine analyses for opioids and cocaine showed
      significantly lower baseline putamen BPND in heroin patients (n = 8) than
      controls (n = 10) (3.19 +/- 0.43 vs. 3.80 +/- 0.64, p = 0.049, d = -1.03). XRNT
      treatment in heroin patients was not significantly associated with changes in
      striatal DAT availability (p = 0.348, d = 0.48), but the mean BDI score after
      XRNT treatment was significantly lower than before treatment (7.75 +/- 7.21 vs.
      12.75 +/- 7.40, p = 0.004, d = -0.68). CONCLUSIONS: The results of this study
      suggest that XRNT treatment does not reduce striatal DAT availability and has no
      significant effect on anhedonia, but is associated with a significant reduction
      of depressive symptoms.

PMID- 25757674
TI  - Reply to Wang and Sadee.

PMID- 25757675
TI  - Improving qPCR telomere length assays: Controlling for well position effects
      increases statistical power.
AB  - OBJECTIVES: Telomere length (TL) is commonly measured using quantitative PCR
      (qPCR). Although, easier than the southern blot of terminal restriction fragments
      (TRF) TL measurement method, one drawback of qPCR is that it introduces greater
      measurement error and thus reduces the statistical power of analyses. To address
      a potential source of measurement error, we consider the effect of well position
      on qPCR TL measurements. METHODS: qPCR TL data from 3,638 people run on a Bio-Rad
      iCycler iQ are reanalyzed here. To evaluate measurement validity, correspondence
      with TRF, age, and between mother and offspring are examined. RESULTS: First, we
      present evidence for systematic variation in qPCR TL measurements in relation to
      thermocycler well position. Controlling for these well-position effects
      consistently improves measurement validity and yields estimated improvements in
      statistical power equivalent to increasing sample sizes by 16%. We additionally
      evaluated the linearity of the relationships between telomere and single copy
      gene control amplicons and between qPCR and TRF measures. We find that, unlike
      some previous reports, our data exhibit linear relationships. We introduce the
      standard error in percent, a superior method for quantifying measurement error as
      compared to the commonly used coefficient of variation. Using this measure, we
      find that excluding samples with high measurement error does not improve
      measurement validity in our study. CONCLUSIONS: Future studies using block-based
      thermocyclers should consider well position effects. Since additional information
      can be gleaned from well position corrections, rerunning analyses of previous
      results with well position correction could serve as an independent test of the
      validity of these results.

PMID- 25757676
TI  - Toward a better management of older patients with acute myeloid leukemia.

PMID- 25757678
TI  - Crizotinib in the management of advanced-stage non-small-cell lung cancer.
AB  - ABSTRACT  Rearrangement of ALK gene has been identified as exerting a potent
      transforming effect as driver oncogene in patients with non-small-cell lung
      cancer (NSCLC). Crizotinib is a small-molecule oral inhibitor of ALK, c-Met/HGF
      receptor and ROS1 receptor kinases. Its efficacy in ALK-rearranged NSCLC has been
      established. Crizotinib's effect on ROS1 receptor kinases and c-Met with
      relevance to NSCLC is also actively being explored. Resistance mechanisms such as
      secondary gatekeeper mutations in ALK gene and activation of other oncogenes have
      been identified to confer acquired resistance to crizotinib. This article reviews
      the pharmacological properties of crizotinib, preclinical and clinical results
      that led to its approval in ALK-positive NSCLC and current directions of clinical
      research in overcoming crizotinib resistance. 

PMID- 25757677
TI  - Efficacy and safety of ruxolitinib in the treatment of patients with
      myelofibrosis.
AB  - The JAK1 and JAK2 inhibitor ruxolitinib has approved indications in
      myelofibrosis, a BCR-AB1-negative myeloproliferative neoplasm associated with
      progressive bone marrow fibrosis and shortened survival. In Phase III clinical
      studies, ruxolitinib provided rapid and durable improvement of myelofibrosis
      related splenomegaly and symptoms irrespective of mutation status, and was
      associated with a survival advantage compared with placebo or best available
      therapy. Because of dose-dependent cytopenias, blood count monitoring and dose
      titration are important to optimize therapy. Specific precautions apply to the
      treatment of patients with or at risk of serious infections. Discontinuation of
      ruxolitinib generally leads to symptom return within 1 week. Ruxolitinib also is
      approved for treatment of patients with polycythemia vera who have had an
      inadequate response to or are intolerant of hydroxyurea.

PMID- 25757679
TI  - Olaparib: an oral PARP-1 and PARP-2 inhibitor with promising activity in ovarian
      cancer.
AB  - Olaparib (LynparzaTM; AZD2281) is a potent PARP-1 and PARP-2 inhibitor with
      biologic activity in ovarian cancer as well as other solid tumors. It has been
      tested in Phase I and II trials and has single-agent activity in both germline
      BRCA mutated and sporadic ovarian cancer. Phase III trials assessing the efficacy
      of olaparib in the maintenance setting following first line and platinum
      sensitive recurrence are underway for patients with a germline BRCA mutation,
      given the inherent molecular compatibility with the drug's mechanism of action.

PMID- 25757680
TI  - Potential and real 'antineoplastic' and metabolic effect of metformin in diabetic
      and nondiabetic postmenopausal females.
AB  - AIM: The goal of this study was to determine if the single nucleotide
      polymorphisms marking potential sensitivity to metformin (MF) correlate with
      hormone-metabolic status as well as with actual response to MF in postmenopausal
      cancer patients with or without Type 2 diabetes mellitus and in diabetics without
      cancer. PATIENTS & METHODS: The carriage of ten different SNPs was evaluated in
      all patients by PCR, and hormone-metabolic status was estimated by anthropometry,
      ELISA and enzyme colorimetric assays. The response to daily 1-1.7 g of MF was
      studied based on hormone-metabolic parameters and indirect end points
      (endometrium thickness, mammographic breast density). RESULTS & CONCLUSION: The
      changes in evaluated 'antineoplastic' and metabolic response marker values were
      seen in 33.3 and 61.8% of the cases, respectively. Several genetic markers were
      found that showed an inclination to less frequent 'antineoplastic' or more
      frequent metabolic response to MF which may be helpful in further studies of this
      drug in cancer patients.

PMID- 25757681
TI  - Intratumoral polymorphonuclear granulocyte is associated with poor prognosis in
      squamous esophageal cancer by promoting epithelial-mesenchymal transition.
AB  - AIM: The role of polymorphonuclear granulocyte (PMN) infiltration in tumor
      remains unclear in esophageal cancer (EC). MATERIALS & METHODS: We conducted a
      retrospective study on consecutive patients with primary squamous EC. The
      potential roles of PMN infiltration into tumor nests were assessed by
      immunohistochemistry. The interactions of PMNs and tumor cells were investigated
      in an in vitro coculture system. RESULTS: Intratumoral PMN is an independent
      prognostic factor. PMN infiltration induces epithelial-mesenchymal transition of
      cancer cells with the initiation of TGF-beta/Smad signaling pathway. CONCLUSION:
      Our study demonstrates intratumoral PMN is an independent unfavorable predictor
      in squamous EC. PMN promotes cancer progression partly by its ability to induce
      epithelial-mesenchymal transition via TGF-beta/Smad signaling pathway.

PMID- 25757682
TI  - A periodic table for cancer.
AB  - Cancers exhibit differences in metastatic behavior and drug sensitivity that
      correlate with certain tumor-specific variables such as differentiation grade,
      growth rate/extent and molecular regulatory aberrations. In practice, patient
      management is based on the past results of clinical trials adjusted for these
      biomarkers. Here, it is proposed that treatment strategies could be fine-tuned
      upfront simply by quantifying tumorigenic spatial (cell growth) and temporal
      (genetic stability) control losses, as predicted by genetic defects of cell-cycle
      regulatory gatekeeper and genome-stabilizing caretaker tumor suppressor genes,
      respectively. These differential quantifications of tumor dysfunction may in turn
      be used to create a tumor-specific 'periodic table' that guides rational
      formulation of survival-enhancing anticancer treatment strategies.

PMID- 25757683
TI  - Future perspectives for mTOR inhibitors in renal cell cancer treatment.
AB  - Everolimus is a mTOR inhibitor that demonstrates antitumor and antiangiogenic
      activities. In a randomized Phase III trial, patients with metastatic renal cell
      carcinoma who progressed on sunitinib/sorafenib were treated with everolimus and
      showed significant improvement in progression-free survival compared with best
      supportive care. Novel approaches in treatment are expected to ensure less toxic
      therapies and increase efficacy of everolimus. To provide a new perspective for
      mTOR inhibitor research and therapy, we discuss renal cell carcinoma cancer stem
      cells as a potential target for mTOR inhibitors and present new concepts on
      emerging antiangiogenic therapies. Finally, we point why systems biology approach
      with reverse molecular engineering may also contribute to the field of drug
      discovery in renal cell carcinoma.

PMID- 25757684
TI  - Clinical trials of stereotactic ablative radiotherapy for prostate cancer:
      updates and future direction.
AB  - Stereotactic body radiotherapy, also known as stereotactic ablative body
      radiotherapy (SABR), is an emerging treatment option for lung, prostate, liver
      and other tumors. Key factors in SABR are delivery of a high-dose radiation per
      fraction, proper patient positioning and target localization. Our review details
      the various radiotherapy techniques, dose fractionation schedules and toxicities
      for prostate SABR. Ongoing Phase II/III SABR studies across various risk groups
      have been included. It also discusses the role of conscientious focal dose
      escalation of the dominant intraprostatic nodule, integrating multiparametric MRI
      into radiotherapy protocols and finally cost-effectiveness of SABR.

PMID- 25757685
TI  - An analysis of the therapeutic benefits of genotyping in pediatric hematopoietic
      stem cell transplantation.
AB  - Hematopoietic stem cell transplantation is a high-risk procedure that is offered,
      with curative intent, to patients with malignant and nonmalignant disease. The
      clinical benefits of personalization of therapy by genotyping have been
      demonstrated by the reduction in transplant related mortality from donor
      recipient HLA matching. However, defining the relationship between genotype and
      transplant conditioning agents is yet to be translated into clinical practice. A
      number of the therapeutic agents used in stem cell transplant preparative
      regimens have pharmacokinetic parameters that predict benefit of incorporating
      pharmacogenomic data into dosing strategies. Busulfan, cyclophosphamide, thio
      TEPA and etoposide have well-described drug metabolism pathways, however
      candidate gene studies have identified there is a gap in the identification of
      pharmacogenomic data that can be used to improve transplant outcomes.
      Incorporating pharmacogenomics into pharmacokinetic modeling may demonstrate the
      therapeutic benefits of genotyping in transplant preparative regimen agents.

PMID- 25757686
TI  - Pancreatic neuroendocrine tumors: a review.
AB  - Neuroendocrine tumors (NETs) are a rare and heterogeneous group of tumors with
      widely varying morphologies and behaviors. Due to their rarity and heterogeneity,
      progress in improving their treatment has been slow. However, in recent years
      there have been advances both in their characterization and in the available
      treatment options. This review will attempt to address these, with particular
      reference to pancreatic NETs. Pancreatic NETs are a subset of NETs, previously
      known as islet cell tumors, which appear to be a distinct biological entity,
      responding differently to systemic treatments compared with NETs arising
      elsewhere in the GI tract.

PMID- 25757688
TI  - SNPs detected in the yak MC4R gene and their association with growth traits.
AB  - MC4R (melanocortin 4 receptor) is expressed in the appetite-regulating areas of
      the brain and takes part in leptin signaling pathways. Sequencing of the coding
      region of the MC4R gene for 354 yaks identified the following five single
      nucleotide polymorphisms (SNPs): SNP1 (273C>T), SNP2 (321 G>T), SNP3 (864 C>A),
      SNP4 (1069G>C) and SNP5 (1206 G>C). SNP1, SNP2 and SNP3 were synonymous
      mutations, whereas SNP4 and SNP5 were missense mutations resulting in amino acid
      substitutions (V286L and R331S). Pairwise linkage disequilibrium (LD) analysis
      indicated that two pairs of SNPs, SNP2 and SNP5 (r(2)=0.81027) and SNP4 and SNP5
      (r(2)=0.53816), exhibited higher degrees of LD. CC genotype of SNP4, CGACG and
      CTCCC haplotypes for all SNPs were associated with increased BW of animals that
      were 18 months old and with the average daily gain. The secondary structure and
      transmembrane region prediction of the yak MC4R protein suggested that SNP4 was
      correlated with influential changes in the seventh transmembrane domain of the
      MC4R protein and with the functional deterioration or even incapacitation of
      MC4R, which may contribute to the increased feed intake, BW and average daily
      gain of the yaks with CC genotypes. The data from this study suggested that
      1069G>C SNP of the MC4R gene could be used in marker-assisted selection of growth
      traits in the Maiwa yak breed.

PMID- 25757689
TI  - The mediodorsal thalamus as a higher order thalamic relay nucleus important for
      learning and decision-making.
AB  - Recent evidence from monkey models of cognition shows that the magnocellular
      subdivision of the mediodorsal thalamus (MDmc) is more critical for learning new
      information than for retention of previously acquired information. Further,
      consistent evidence in animal models shows the mediodorsal thalamus (MD)
      contributes to adaptive decision-making. It is assumed that prefrontal cortex
      (PFC) and medial temporal lobes govern these cognitive processes so this evidence
      suggests that MD contributes a role in these cognitive processes too.
      Anatomically, the MD has extensive excitatory cortico-thalamo-cortical
      connections, especially with the PFC. MD also receives modulatory inputs from
      forebrain, midbrain and brainstem regions. It is suggested that the MD is a
      higher order thalamic relay of the PFC due to the dual cortico-thalamic inputs
      from layer V ('driver' inputs capable of transmitting a message) and layer VI
      ('modulator' inputs) of the PFC. Thus, the MD thalamic relay may support the
      transfer of information across the PFC via this indirect thalamic route. This
      review summarizes the current knowledge about the anatomy of MD as a higher order
      thalamic relay. It also reviews behavioral and electrophysiological studies in
      animals to consider how MD might support the transfer of information across the
      cortex during learning and decision-making. Current evidence suggests the MD is
      particularly important during rapid trial-by-trial associative learning and
      decision-making paradigms that involve multiple cognitive processes. Further
      studies need to consider the influence of the MD higher order relay to advance
      our knowledge about how the cortex processes higher order cognition. 

PMID- 25757687
TI  - Current and future targeted therapies for non-small-cell lung cancers with
      aberrant EGF receptors.
AB  - Expression of the EGF receptors (EGFRs) is abnormally high in many types of
      cancer, including 25% of lung cancers. Successful treatments target mutations in
      the EGFR tyrosine kinase domain with EGFR tyrosine kinase inhibitors (TKIs).
      However, almost all patients develop resistance to this treatment, and acquired
      resistance to first-generation TKI has prompted the clinical development of a
      second generation of EGFR TKI. Because of the development of resistance to
      treatment of TKIs, there is a need to collect genomic information about EGFR
      levels in non-small-cell lung cancer patients. Herein, we focus on current
      molecular targets that have therapies available as well as other targets for
      which therapies will be available in the near future.

PMID- 25757690
TI  - [Complication management of the lower gastrointestinal tract].

PMID- 25757691
TI  - Potential roles of laccases on virulence of Heterobasidion annosum s.s.
AB  - Laccases, multi-copper-containing proteins, can catalyze the oxidation of
      phenolic substrates and have diverse functions such as a virulence factor in
      fungi. However, limited information can be found on the role of laccases in the
      interaction of Heterobasidion annosum s.s. to its host plant. Due to genome
      availability of the close-related species Heterobasidion irregulare, which
      contains 18 predicted laccase-encoding genes, phylogenetic analysis and gene
      expression profiling were performed. Eighteen laccase genes could be classified
      into 4 groups based on protein domains and phylogenetic analysis. However, there
      is no clear indication between phylogeny and domain compositions in laccases, and
      lifestyles of fungal species. The results of qRT-PCR showed that the expression
      of 8 laccase genes was highly up-regulated in Scots pine seedlings at 1 wpi.
      These data suggested that they might be involved in early stage of host
      infection. In addition, up-regulation of gene expression under glucose condition
      as a sole carbon source suggests that those laccases are not under carbon
      catabolite repression. Higher activities of laccase were observed in culture
      media containing cellulose, sucrose, or glucose compared to that of cellobiose as
      a sole carbon source. The highest mortality of Scots pine seedlings was observed
      when infected by H. annosum s.s. on extra carbon source as glucose. This was
      supported by the facts that glucose plays significant roles on up-regulation of
      laccase genes in planta and higher activity of laccase in H. annosum s.s.. Taking
      all together, laccases in H. annosum s.s. have diverse functions and a group of
      laccases may play a role during interactions with Scots pine seedlings. 

PMID- 25757692
TI  - [Knowledge of electronic cigarettes and their perceived harmfulness among the
      adult population in Barcelona (Spain)].
AB  - OBJECTIVE: To describe knowledge of electronic cigarettes (e-cigarettes) and
      their perceived harmfulness in the population of Barcelona in 2013-2014. METHODS:
      We used participants from a longitudinal study of a representative sample of the
      adult population in the city of Barcelona (n=736). The field work was conducted
      between May 2013 and February 2014. RESULTS: Awareness of e-cigarette was 79.2%.
      The average level of knowledge was 4.4 points out of 10; there were statistically
      significant differences according to age, educational level, tobacco consumption,
      and nicotine dependence. Most participants had learned about e-cigarettes through
      traditional media (57.8%). Nearly half (47.2%) of the participants believed that
      e-cigarettes are less harmful than conventional cigarettes. CONCLUSION:
      Advertising of e-cigarettes in the media should be regulated because there is
      still scarce scientific evidence about the usefulness and harmful effects of
      these devices.

PMID- 25757693
TI  - The East tennessee assertive adolescent family treatment program: a three-year
      evaluation.
AB  - The Assertive Adolescent Family Treatment Program targeted adolescents defined as
      age 12 to 17 years and transition age youth (age 18-24) who were served by the
      Helen Ross McNabb Center Regional Mental Health System. Most of the participating
      individuals met the Diagnostic and Statistical Manual of Mental Disorders(IV-TR)
      criteria for substance abuse or substance dependence and co-occurring mental
      health disorder. Significant findings in the study included a decrease in illegal
      drug use, decrease in alcohol consumption, decrease in criminal activity,
      decrease in violent behaviors, and an increase in cognitive ability. Other
      findings indicated a decrease in risky sexual behaviors and an increase in
      participant interaction with supportive friends and family. This study indicates
      success of the Assertive Adolescent Family Treatment Program and the intervention
      models used. More research is needed in East Tennessee to generalize the findings
      and establish a stronger evidence base. 

PMID- 25757694
TI  - Synthesis and thermal behavior of tin-based alloy (Sn-Ag-Cu) nanoparticles.
AB  - The prominent melting point depression of nanoparticles has been the subject of a
      considerable amount of research. For their promising applications in electronics,
      tin-based nano-alloys such as near-eutectic Sn-Ag-Cu (SAC) alloys have been
      synthesized via various techniques. However, due to issues such as particle
      aggregation and oxidation or introduced impurities, the application of these nano
      size particles has been confined or aborted. For instance, thermal investigations
      by DTA/DSC in a large number of studies revealed exothermic peaks in the range of
      240-500  degrees C, i.e. above the melting point of SAC nanoparticles, with
      different and quite controversial explanations for this unclear phenomenon. This
      represents a considerable drawback for the application of nanoparticles.
      Correspondingly, in the current study, the thermal stability of SAC nanoparticles
      has been investigated via electron microscopy, XRD, FTIR, and DSC/TG analysis. It
      was found that the nanoparticles consist mainly of a metallic beta-Sn core and an
      amorphous tin hydroxide shell structure. The SnO crystalline phase formation from
      this amorphous shell has been associated with the exothermic peaks on the first
      heating cycle of the nanoparticles, followed by a disproportionation reaction
      into metallic Sn and SnO2.The results also revealed that the surfactant and
      reducing agent cannot only affect the size and size distribution of the
      nanoparticles, they might also alter the ratio between the amorphous shell and
      the crystalline core in the structure of particles.

PMID- 25757695
TI  - Anatomic locking plate and coracoclavicular stabilization with suture endo-button
      technique is superior in the treatment of Neer Type II distal clavicle fractures.
AB  - INTRODUCTION: The purpose of this retrospective study was to compare the clinical
      results of three different fixation techniques for the treatment of Neer Type IIb
      fractures. We hypothesized that anatomic locking plate and coracoclavicular
      stabilization with suture endo-button technique provides more stable and
      biomechanically superior fixation among others with low complication rates.
      METHODS: Thirty six patients with Neer Type IIb fractures treated were evaluated.
      Patients were divided into three groups according to surgical choice that was
      performed: tension band and coracoclavicular suture stabilization with k-wires
      was defined as Group 1, anatomic locking plate and coracoclavicular stabilization
      with screw was defined as Group 2, and anatomic locking plate and
      coracoclavicular stabilization with suture endo-button (LPES) was defined as
      group 3. Mean age was 36.1 years, and mean follow-up period was 32.4 months.
      Radiological follow-ups and constant were recorded and compared at 3, 6, 12 and
      24 months. RESULTS: At 3rd and 12th month follow-up in the LPES group, mean
      constant scores were statistically higher than other two groups (p < 0.01). The
      difference between other two groups was insignificant (p > 0.05). At 6th month
      follow-up, mean constant scores in LPES group were higher than other groups;
      there was less statistical significance than other time zones (p < 0.05).
      CONCLUSION: Anatomic locking plate combined with suture endo-button for CC
      ligament reinforcement is a reliable method to achieve osteosynthesis and
      stabilization for Neer Type IIb distal clavicle fractures without compromising
      physiology of shoulder.

PMID- 25757696
TI  - Anatomic physeal-sparing technique for medial patellofemoral ligament
      reconstruction in skeletally immature patients with ligamentous laxity.
AB  - PURPOSE: To evaluate the clinical outcome of this modified physeal-sparing
      technique for MPFL reconstruction in skeletally immature patients with ligament
      laxity. PATIENTS AND METHODS: This study was conducted on 16 patients (11 females
      and 5 males) with an average age of 11.5 years (8-15). They all had recurrent
      patellar dislocation with generalized ligament laxity (mean Beighton's score of
      7) and no patellar tilt on X-ray. We modified the Frank Noyes' non-anatomic
      technique for MPFL reconstruction to become anatomic without hardware fixation
      for the graft. RESULTS: The mean follow-up period was 29.25 months (SD 4.3)
      ranged from 24 to 34 months. Preoperative Kujala score had ranged from 49 to 61
      points (mean of 56, SD 4.72), improved to be ranged from 90 to 99 points (mean
      94, SD 2.73), which is considered highly significant (p value < 0.005). Till the
      latest follow-up, there were no definite re-dislocation episodes in any of our
      patients. CONCLUSION: The described technique allows reconstruction of the MPFL
      in skeletally immature patients with ligament laxity avoiding any potential risks
      of growth disturbances or chondral damage as compared to other techniques. The
      modification of two-point femoral fixation allows both a more anatomic and more
      secure form of reconstruction and is cost-effective without the need for
      hardware.

PMID- 25757697
TI  - Identification of a novel HLA allele, HLA-B*53:39, in a Guadaloupean individual.
AB  - The novel HLA-B*53:39 allele differs from HLA-B*53:01 by a single nucleotide
      substitution at codon 45 (ACG>AAG). 

PMID- 25757698
TI  - Observation of antibacterial effect of biodegradable polymeric nanoparticles on
      Staphylococcus epidermidis biofilm using FE-SEM with an ionic liquid.
AB  - We successfully visualized the antibacterial behavior of biodegradable polymeric
      nanoparticles (NPs) on a biofilm formed by Staphylococcus epidermidis using field
      emission scanning electron microscopy (FE-SEM). A hydrophilic ionic liquid, 1
      butyl-3-methylimidazolium tetrafluoroborate ([BMIM][BF4]), was applied for
      observation using FE-SEM. The differences in adherence and penetration behavior
      of three types of NPs were revealed using this method and confocal laser scanning
      microscopy. Biodegradable poly(dl-lactide-co-glycolide) (PLGA) NPs were prepared
      by the emulsion solvent diffusion method. In this study, we treated the biofilm
      with three PLGA NPs: unmodified PLGA, PLGA modified with chitosan (CS) and
      clarithromycin (CAM)-loaded + CS-modified PLGA. The viability of S. epidermidis
      cells treated with PLGA NPs was estimated using the LIVE/DEAD BacLight kit to
      understand the antibacterial ability of each NP sample in a quantitative way. The
      results confirmed that CAM-loaded + CS-modified PLGA had high antibacterial
      ability on the biofilm. This novel observation technique would be useful in the
      development of drug formations and medical agents. 

PMID- 25757699
TI  - Aromatase inhibitors, tamoxifen, and endometrial cancer in breast cancer
      survivors.
AB  - BACKGROUND: The risks of both endometrial cancer and postmenopausal breast cancer
      are increased by obesity and higher endogenous estrogen levels. Although
      aromatase inhibitors reduce breast cancer incidence, their influence on
      endometrial cancer is uncertain. METHODS: The authors investigated this issue in
      a cohort of 17,064 women who were diagnosed with hormone receptor-positive breast
      cancer in an integrated group practice health plan. Information on demographics,
      comorbidities, and the receipt of adjuvant endocrine therapy was available from
      electronic medical records and pharmacy records, respectively. Endometrial cancer
      information was obtained from the health plan's Surveillance, Epidemiology, and
      End Results-affiliated tumor registry, and rates were compared across endocrine
      therapy groups (aromatase inhibitor, n = 5303; tamoxifen, n = 5155; switchers:
      both [n = 3787] or none [n = 2819]) using multivariable adjusted Cox proportional
      hazards models. RESULTS: Endometrial cancer incidence was a statistically
      significant 48% lower in the aromatase inhibitor group versus the tamoxifen group
      (hazard ratio, 0.52; 95% confidence interval, 0.31-0.87; P = .01). Endometrial
      cancer incidence was 29% lower in the aromatase inhibitor group versus the no
      endocrine therapy group (hazard ratio, 0.71; 95% confidence interval, 0.37-1.35;
      P = .30) and 33% lower in the aromatase inhibitor group versus the tamoxifen
      group (hazard ratio, 0.67; 95% confidence interval, 0.42-1.06; P = .08), but
      neither difference was statistically significant. Associations were stronger
      among those with good drug adherence. CONCLUSIONS: In a community-based,
      integrated health plan setting, endometrial cancer incidence was lower in women
      who were receiving an aromatase inhibitor compared with those who were receiving
      tamoxifen. In addition, aromatase inhibitors may mitigate the incidence of
      tamoxifen-associated endometrial cancer. Although there were somewhat fewer
      endometrial cancers in the aromatase inhibitor group versus the no endocrine
      therapy group, further studies are needed for the definitive assessment of this
      potential association.

PMID- 25757700
TI  - NHS trusts in England agree 2015-16 tariff but face ongoing budget pressure.

PMID- 25757701
TI  - World hospital pharmacy research consortium.

PMID- 25757702
TI  - Re: tackling tobacco smoking: opportunities for pharmacists.

PMID- 25757703
TI  - Advancing into a future hospital pharmacy practice model: the value of the Basel
      Statements.

PMID- 25757704
TI  - Palladium(II)-1-phenylthio-2-arylchalcogenoethane complexes: palladium phosphide
      nano-peanut and ribbon formation controlled by chalcogen and Suzuki coupling
      activation.
AB  - The ligands PhSCH2CH2EAr (; E = S, Se or Te) and their Pd-complexes [PdLCl2] ()
      have been synthesized and authenticated with their (1)H, (13)C{(1)H},
      (77)Se{(1)H} and (125)Te{(1)H} NMR spectra. Single crystal structures of and
      reveal the geometry of donor atoms around palladium as nearly square planar.
      Thermolysis of all three complexes in trioctylphosphine (TOP) at 350, 320 and 280
      degrees C, respectively, results in a single phase of crystalline PdP2. The
      morphology of the phase varies with 'E' to some extent. The nanopeanuts (size ~30
      and ~35 nm) were formed with and as precursor complexes. On using complex as a
      precursor nanoribbons are formed. The preferential growth in the (202) plane in
      the case of all the three precursor complexes has been rationalized in terms of
      texture coefficient and average crystallite size. All three complexes and PdP2
      NPs have been explored for Suzuki-Miyaura coupling of several aryl halides.
      Complexes and show good catalytic activity but complex does not. The activity
      appears to result due to in situ generated palladium containing nanoparticles
      (NPs) in the case of and . The formation of inactive large Pd aggregates in the
      case of appears to be responsible for the difference. The PdP2 NPs have been
      found to show good catalytic activity and recyclability up to six reaction
      cycles. The results of the three phase test suggest the involvement of both
      homogeneous and heterogeneous pathways in the activation of Suzuki coupling. DFT
      based free energy calculations are consistent with the results of catalysis via
      Pd(0) protected with the ligand. This palladium may also be released from in situ
      generated NPs. In the case of , negligible reactivity may be due to non-release
      of Pd. 

PMID- 25757705
TI  - Recommendations for the development of rare disease drugs using the accelerated
      approval pathway and for qualifying biomarkers as primary endpoints.
AB  - For rare serious and life-threatening disorders, there is a tremendous challenge
      of transforming scientific discoveries into new drug treatments. This challenge
      has been recognized by all stakeholders who endorse the need for flexibility in
      the regulatory review process for novel therapeutics to treat rare diseases. In
      the United States, the best expression of this flexibility was the creation of
      the Accelerated Approval (AA) pathway. The AA pathway is critically important for
      the development of treatments for diseases with high unmet medical need and has
      been used extensively for drugs used to treat cancer and infectious diseases like
      HIV.In 2012, the AA provisions were amended to enhance the application of the AA
      pathway to expedite the development of drugs for rare disorders under the Food
      and Drug Administration Safety and Innovation Act (FDASIA). FDASIA, among many
      provisions, requires the development of a more relevant FDA guidance on the types
      of evidence that may be acceptable in support of using a novel surrogate
      endpoint. The application of AA to rare diseases requires more predictability to
      drive greater access to appropriate use of AA for more rare disease treatments
      that might not be developed otherwise.This white paper proposes a scientific
      framework for assessing biomarker endpoints to enhance the development of novel
      therapeutics for rare and devastating diseases currently without adequate
      treatment and is based on the opinions of experts in drug development and rare
      disease patient groups. Specific recommendations include: 1) Establishing
      regulatory rationale for increased AA access in rare disease programs; 2)
      Implementing a Biomarker Qualification Request Process to provide the opportunity
      for an early determination of biomarker acceptance; and 3) A proposed scientific
      framework for qualifying biomarkers as primary endpoints. The paper's final
      section highlights case studies of successful examples that have incorporated
      biomarker endpoints into FDA approvals for rare disease therapies. The focus of
      this paper is on the situation in the Unites States, but the recommendations are
      reasonably applicable to any jurisdiction. 

PMID- 25757707
TI  - Synthesis of dibenzo[c,e]oxepin-5(7H)-ones from benzyl thioethers and carboxylic
      acids: rhodium-catalyzed double C-H activation controlled by different directing
      groups.
AB  - A rhodium(III)-catalyzed cross-coupling of benzyl thioethers and aryl carboxylic
      acids through the two directing groups is reported. Useful structures with
      diverse substituents were efficiently synthesized in one step with the cleavage
      of four bonds (C?H, C?S, O?H) and the formation of two bonds (C?C, C?O). The
      formed structure is the privileged core in natural products and bioactive
      molecules. This work highlights the power of using two different directing groups
      to enhance the selectivity of a double C?H activation, the first of such examples
      in cross-oxidative coupling. 

PMID- 25757706
TI  - Molecular phylogeny and ultrastructure of the lichen microalga Asterochloris
      mediterranea sp. nov. from Mediterranean and Canary Islands ecosystems.
AB  - The microalgae of the genus Asterochloris are the preferential phycobionts in
      Cladonia, Lepraria and Stereocaulon lichens. Recent studies have highlighted the
      hidden diversity of the genus, even though phycobionts hosting species of the
      genus Cladonia in Mediterranean and Canarian ecosystems have been poorly
      explored. Phylogenetic analyses were made by concatenation of the sequences
      obtained with a plastid - LSU rDNA - and two nuclear - internal transcribed
      spacer (ITS) rDNA and actin - molecular markers of the phycobionts living in
      several populations of the Cladonia convoluta-Cladonia foliacea complex, Cladonia
      rangiformis and Cladonia cervicornis s. str. widely distributed in these areas in
      a great variety of substrata and habitats. A new strongly supported clade was
      obtained in relation to the previously published Asterochloris phylogenies.
      Minimum genetic variation was detected between our haplotypes and other sequences
      available in the GenBank database. The correct identification of the fungal
      partners was corroborated by the ITS rDNA barcode. In this study we provide a
      detailed characterization comprising chloroplast morphology, and ultrastructural
      and phylogenetic analyses of a novel phycobiont species, here described as
      Asterochloris mediterranea sp. nov. Barreno, Chiva, Moya et Skaloud. A
      cryopreserved holotype specimen has been deposited in the Culture Collection of
      Algae of Charles University in Prague, Czech Republic (CAUP) as CAUP H 1015. We
      suggest the use of a combination of several nuclear and plastid molecular
      markers, as well as ultrastructural (transmission electron and confocal
      microscopy) techniques, both in culture and in the symbiotic state, to improve
      novel species delimitation of phycobionts in lichens. 

PMID- 25757708
TI  - Prison staff and the health promoting prison.
AB  - PURPOSE: This paper aims to discuss some of the obstacles to implementing policy
      and strategy related to health promoting prisons. It focuses on the role of
      prison officers and raises issues concerning their conditions of service,
      training and organisational culture in a situation where the prison system faces
      security issues, overcrowding and high levels of ill health among prisoners.
      DESIGN/METHODOLOGY/APPROACH: This paper emerged as a result of significant
      overlapping themes between two separate studies conducted by the authors. The
      paper draws on the authors' qualitative data from these studies. FINDINGS: The
      findings demonstrate the ambiguities and tensions in changing organisational
      cultures and among prison staff. Alongside the qualitative data, the paper draws
      on theory regarding policy implementation at the micro-level to show how staff
      can block or speed up that implementation. PRACTICAL IMPLICATIONS: Prison
      officers are an essential part of health promoting prisons, but have been
      relatively ignored in the discussion of how to create healthier prisons.
      ORIGINALITY/VALUE: The contribution that prison staff make to creating health
      promoting prisons has been under-explored, yet pertinent theory can show how they
      can be more effectively involved in making changes in organisational culture.

PMID- 25757709
TI  - Childhood maltreatment and mental disorders among Finnish prisoners.
AB  - PURPOSE: In a health survey of Finnish prisoners in 2006, the authors aimed to
      study frequency and gender differences in childhood physical and sexual abuse,
      and the connections of maltreatment in childhood to substance abuse and mental
      health among female and male prisoners. DESIGN/METHODOLOGY/APPROACH: The sample
      consisted of 101 female prisoners, with 309 male prisoners for comparison. The
      subjects participated in a comprehensive field study consisting of several
      questionnaires, interviews, the Structured Clinical Interview for DSM-IV Axis I
      and II Disorders (SCID I, II) and a clinical medical examination including ICD-10
      diagnoses. FINDINGS: Both forms of abuse were more common among females than
      males (childhood physical abuse 25 per cent versus 15 per cent and childhood
      sexual abuse 32 per cent versus 7 per cent). Associations of childhood abuse with
      substance abuse and mental health were different among males and females. Family
      integrity was important only for males and in connection with drug dependence and
      antisocial personality disorder. The gender differences did not concur with those
      reported in studies on general populations. ORIGINALITY/VALUE: This is a part of
      the first comprehensive health survey of Finnish prisoners.

PMID- 25757710
TI  - Beyond reintegration: a framework for understanding ex-prisoner health.
AB  - PURPOSE: This paper proposes a framework to better understand ex-prisoner health,
      and pilot-tests the framework using qualitative interviews with ten people who
      have been out of prison for two years or more. The proposed framework considers
      different stages of re-entry (from pre-incarceration through to post-release),
      individual and structural factors influencing health, and health outcomes.
      DESIGN/METHODOLOGY/APPROACH: The authors conducted qualitative, open-ended
      interviews with ex-prisoners released from prison two or more years ago, who
      could be considered to have transitioned "successfully" out of prison. The aim of
      the interviews was to generate insights into the strategies that ex-prisoners use
      to negotiate the post-release period. FINDINGS: Most of the themes that emerged
      from interviews were consistent with the proposed framework. Structural factors
      are important concerns for ex-prisoners that may have to be resolved before other
      issues, such as drug addiction, can be addressed. However, these findings suggest
      that it is inappropriate to view health-related experiences during re-entry as
      homogenous, given the diversity of individual characteristics and backgrounds
      among ex-prisoners, notably including pre-incarceration social status.
      ORIGINALITY/VALUE: To explain the health-related experiences of people following
      their release from prison, we need to think beyond reintegration and move beyond
      homogenous notions of the ex-prisoner population. Addressing sociocultural,
      demographic and incarceration-specific factors that ameliorate or intensify the
      challenges faced by ex-prisoners is of critical importance.

PMID- 25757711
TI  - Peer health promotion in prisons: a systematic review.
AB  - PURPOSE: The purpose of this paper is to review systematically the available
      literature relating to the implementation of peer education to promote health and
      healthy behaviour in prisons. DESIGN/METHODOLOGY/APPROACH: The authors undertook
      a narrative systematic review of Medline, EMBASE, CINAHL, Psychinfo, Web of
      Science and Cochrane databases. Relevant journals and reference lists were hand
      searched for relevant articles to be included in the review. Of the abstracts
      found, full-text papers were retrieved for those papers deemed as possibly
      fulfilling the inclusion criteria of the review. FINDINGS: A total of 3,033
      abstracts were identified leading to 46 full-text articles being retrieved, of
      which ten were included in the review. Peer education in prisons can have an
      impact on attitudes, knowledge, and behaviour intention regarding HIV risk
      behaviour. The research findings were inconclusive for the impact of peer
      education upon illicit drug use and injecting practice. There was a paucity of
      research evaluating the impact of peer education upon mental ill health, obesity,
      diet, smoking, or self-management of chronic physical diseases.
      ORIGINALITY/VALUE: Peer education is effective in reducing risk of HIV
      transmission. It is possible that peer education for mental health issues is
      stigmatising, presenting an opportunity for further research activity. The impact
      of peer education upon illicit drug use practice, obesity, diet, smoking, and
      self-management of chronic physical diseases also presents further research
      opportunities. Research evaluating models of active peer educator involvement in
      health service delivery and organisation is also lacking.

PMID- 25757712
TI  - Subjective effects of prisoners using buprenorphine for detoxification.
AB  - PURPOSE: Buprenorphine (Subutex) was piloted in two Scottish prisons between 2004
      and 2006 and consequently used within other penal establishments in Scotland.
      This 2007 qualitative study aimed to explore the use of Subutex and its
      associated effects on 14 participants on detoxification programmes.
      DESIGN/METHODOLOGY/APPROACH: All participants were male, aged from 21 to 44 years
      with prison sentences ranging from a few months to life imprisonment.
      Buprenorphine was unavailable to female prisoners at the time of this study.
      Participants were recruited from seven Scottish prisons. All 14 participants were
      on detoxification programmes, each was prescribed Subutex, and each was selected
      from a larger investigation that included both those undergoing detoxification
      and maintenance (n=21). All participants had previously also used methadone on
      previous detoxification programmes. FINDINGS: It can be concluded that the
      majority of detoxification participants within this study indicated that Subutex
      was a more effective treatment than methadone as it helped reduce craving, eased
      the process of withdrawal and improved sleeping patterns. In addition, the
      majority of participants noted higher levels of motivation and the ability to set
      goals towards obtaining an improved quality of life. ORIGINALITY/VALUE: This
      study provides an alternative perspective to the use of Subutex within prison
      settings, when compared with results from previous quantitative studies reported.
      The study also highlights inconsistencies drawn from studies in this area, which
      may be an artefact of study design. It is recommended that further qualitative
      studies be conducted to explore further this alternative perspective. Finally,
      the issue of methodological approach taken should be addressed within the context
      of a related, but independent, research forum.

PMID- 25757713
TI  - Dopamine D2/3 receptor availability in the striatum of antipsychotic-free older
      patients with schizophrenia-A [11C]-raclopride PET study.
AB  - BACKGROUND: No study has examined dopamine D2/3 receptor (D2/3R) availability in
      antipsychotic-free older patients with schizophrenia. METHODS: We included
      patients with schizophrenia 50 years or older who were antipsychotic-free for at
      least 3 months. We compared non-displaceable binding potential (BPND) of [(11)C]
      raclopride in the caudate, putamen, ventral striatum, and globus pallidus between
      patients and age- and sex-matched healthy controls. RESULTS: Ten patients
      participated (antipsychotic-naive=4). No differences in BPND were found between
      patients and controls in any ROIs (F(1, 72)=.42, p=.52). CONCLUSION: The
      preliminary results suggest no differences in D2/3R availability between
      antipsychotic-free older patients with schizophrenia and controls.

PMID- 25757714
TI  - Brief culturally adapted CBT for psychosis (CaCBTp): A randomized controlled
      trial from a low income country.
AB  - Evidence for the effectiveness of Culturally adapted CBT for psychosis in Low And
      Middle Income Countries (LAMIC) is limited. Therefore, brief Culturally adapted
      CBT for psychosis (CaCBTp) targeted at symptoms of schizophrenia for outpatients
      plus treatment as usual (TAU) is compared with TAU. A total of 116 participants
      with schizophrenia were recruited from 2 hospitals in Karachi, Pakistan, and
      randomized into two groups with 1:1 allocation (CaCBTp plus TAU=59, TAU=57). A
      brief version of CaCBTp (6 individual sessions with the involvement of main
      carer, plus one session for the family) was provided over 4months.
      Psychopathology was measured using Positive and Negative Syndrome Scale of
      Schizophrenia (PANSS), Psychotic Symptom Rating Scales (PSYRATS), and the
      Schedule for Assessment of Insight (SAI) at baseline and end of therapy.
      Participants in treatment group, showed statistically significant improvement in
      all measures of psychopathology at the end of the study compared with control
      group. Participants in treatment group showed statistically significant
      improvement in Positive Symptoms (PANSS, Positive Symptoms Subscale; p=0.000),
      Negative Symptoms (PANSS, Negative Symptoms subscales; p=0.000), Delusions
      (PSYRATS, Delusions Subscale; p=0.000), Hallucinations (PSYRATS, Hallucination
      Subscale; p=0.000) and Insight (SAI; p=0.007). The results suggest that brief,
      Culturally adapted CBT for psychosis can be an effective treatment when provided
      in combination with TAU, for patients with schizophrenia in a LAMIC setting. This
      is the first trial of CBT for psychosis from outside the western world. These
      findings need replicating in other low and middle income countries. 

PMID- 25757716
TI  - Cation-induced pesticide binding and release by a functionalized calix[4]arene
      molecular host.
AB  - Ion-controlled switchable progress is very important in many biological
      behaviors. Here, we reported K(+)-controlled switch, this switch system exhibited
      excellent carbaryl (G) binding/release by fluorescent (FL), ultraviolet-visible
      (UV) spectrums and (1)H NMR spectroscopy. More importantly, the K(+)-controlled G
      binding/release switch based on C4C5 not only in the solution, but also on the
      surface, promising for the application for the pesticide controlled release. 

PMID- 25757715
TI  - Altered prefrontal cortical MARCKS and PPP1R9A mRNA expression in schizophrenia
      and bipolar disorder.
AB  - BACKGROUND: We previously observed dendritic spine loss in the dorsolateral
      prefrontal cortex (DLPFC) from schizophrenia and bipolar disorder subjects. In
      the current study, we sought to determine if the mRNA expression of genes known
      to regulate the actin cytoskeleton and spines correlated with spine loss.
      METHODS: Five candidate genes were identified using previously obtained
      microarray data from the DLPFC from schizophrenia and control subjects. The
      relative mRNA expression of the genes linked to dendritic spine growth and
      function, i.e. IGF1R, MARCKS, PPP1R9A, PTPRF, and ARHGEF2, was assessed using
      quantitative real-time PCR (qRT-PCR) in the DLPFC from a second cohort including
      schizophrenia, bipolar disorder, and control subjects. Functional pathway
      analysis was conducted to determine which actin cytoskeleton-regulatory pathways
      the genes of interest interact with. RESULTS: MARCKS mRNA expression was
      increased in both schizophrenia and bipolar disorder subjects. PPP1R9A mRNA
      expression was increased in bipolar disorder subjects. For IGF1R, mRNA expression
      did not differ significantly among groups; however, it did show a significant,
      negative correlation with dendrite length. MARCKS and PPP1R9A mRNA expression did
      not correlate with spine loss, but they interact with NMDA receptor signaling
      pathways that regulate the actin cytoskeleton and spines. CONCLUSIONS: MARCKS and
      PPP1R9A might contribute to spine loss in schizophrenia and bipolar disorder
      through their interactions, possibly indirect ones, with NMDA signaling pathways
      that regulate spine structure and function.

PMID- 25757717
TI  - Deeply reinverted T wave at 14 days after the onset of first anterior acute
      myocardial infarction predicts improved left ventricular function at 6 months.
AB  - BACKGROUND: Changes in electrocardiogram (ECG), especially in the ST segment and
      T wave, have been recognized as a noninvasive diagnostic tool for coronary flow
      or myocardial injury. HYPOTHESIS: A deeply inverted T wave at 14 days after
      successful percutaneous coronary intervention (PCI) in patients with ST-segment
      elevation acute myocardial infarction (STEMI) predicts improved left ventricular
      (LV) function at 6 months. METHODS: We enrolled 112 consecutive patients (88 men,
      63 +/- 11 years) with first anterior STEMI who underwent successful PCI. A 12
      lead ECG was recorded everyday from admission through 14 days. After PCI, the
      first T-wave inversion was observed within 2 days, and the second occurred at 14
      days. We measured the maximum depth of the reinverted T wave (Neg-T) and divided
      the patients into 2 groups based on the median value of Neg-T: the deep group
      (>=0.6 mV, n = 62) and the nondeep group (<0.6 mV, n = 50). RESULTS: LV ejection
      fraction (LVEF) at 14 days did not differ between the 2 groups, but it was
      greater in the deep than in the nondeep group at 6 months (50.0% +/- 8.8% vs
      42.5% +/- 9.8 %, P < 0.0001). The maximum creatinine phosphokinase-myocardial
      band (CPK-MB) value was significantly lower in the deep than in the nondeep
      group. Reappearance of the R wave in precordial leads at 6 months was more
      frequently observed in the deep than in the nondeep group (68% vs 46%, P = 0.02).
      Multivariate regression analysis showed that the Neg-T and max CPK-MB were
      independent contributors to LVEF at 6 months. CONCLUSIONS: A deeply reinverted T
      wave at 14 days after onset of first anterior STEMI can be a useful predictive
      marker for improved LV function at 6 months.

PMID- 25757718
TI  - Feminine ideology and sexual assault: are more traditional college women at
      greater risk?
AB  - Previous research has not conclusively determined whether traditional femininity
      increases women's risk for sexual assault. Certain femininity beliefs, such as
      valuing deference, may increase risk for sexual assault by discouraging sexual
      refusal assertiveness (SRA). Other femininity beliefs, such as valuing purity,
      may promote self-protective behaviors. College women (N = 254) provided self
      report data on these beliefs, risk and protective behaviors, and sexual assault
      experiences. Traditional femininity was not directly associated with experiencing
      sexual assault. However, specific traditional beliefs were related to behaviors
      directly associated with risk. High SRA and sexual abstinence simultaneously
      reduced the odds for sexual assault. 

PMID- 25757719
TI  - Letter to the Editor.

PMID- 25757721
TI  - Validation of existing diagnosis of autism in mainland China using standardised
      diagnostic instruments.
AB  - Research to date in mainland China has mainly focused on children with autistic
      disorder rather than Autism Spectrum Conditions and the diagnosis largely
      depended on clinical judgment without the use of diagnostic instruments. Whether
      children who have been diagnosed in China before meet the diagnostic criteria of
      Autism Spectrum Conditions is not known nor how many such children would meet
      these criteria. The aim of this study was to evaluate children with a known
      diagnosis of autism in mainland China using the Autism Diagnostic Observation
      Schedule and the Autism Diagnostic Interview-Revised to verify that children who
      were given a diagnosis of autism made by Chinese clinicians in China were mostly
      children with severe autism. Of 50 children with an existing diagnosis of autism
      made by Chinese clinicians, 47 children met the diagnosis of autism on the Autism
      Diagnostic Observation Schedule algorithm and 44 children met the diagnosis of
      autism on the Autism Diagnostic Interview-Revised algorithm. Using the Gwet's
      alternative chance-corrected statistic, the agreement between the Chinese
      diagnosis and the Autism Diagnostic Observation Schedule diagnosis was very good
      (AC1 = 0.94, p < 0.005, 95% confidence interval (0.86, 1.00)), so was the
      agreement between the Chinese diagnosis and the Autism Diagnostic Interview
      Revised (AC1 = 0.91, p < 0.005, 95% confidence interval (0.81, 1.00)). The
      agreement between the Autism Diagnostic Observation Schedule and the Autism
      Diagnostic Interview-Revised was lower but still very good (AC1 = 0.83, p <
      0.005). 

PMID- 25757720
TI  - Adipose tissue NAPE-PLD controls fat mass development by altering the browning
      process and gut microbiota.
AB  - Obesity is a pandemic disease associated with many metabolic alterations and
      involves several organs and systems. The endocannabinoid system (ECS) appears to
      be a key regulator of energy homeostasis and metabolism. Here we show that
      specific deletion of the ECS synthesizing enzyme, NAPE-PLD, in adipocytes induces
      obesity, glucose intolerance, adipose tissue inflammation and altered lipid
      metabolism. We report that Napepld-deleted mice present an altered browning
      programme and are less responsive to cold-induced browning, highlighting the
      essential role of NAPE-PLD in regulating energy homeostasis and metabolism in the
      physiological state. Our results indicate that these alterations are mediated by
      a shift in gut microbiota composition that can partially transfer the phenotype
      to germ-free mice. Together, our findings uncover a role of adipose tissue NAPE
      PLD on whole-body metabolism and provide support for targeting NAPE-PLD-derived
      bioactive lipids to treat obesity and related metabolic disorders. 

PMID- 25757722
TI  - A highly concentrated catholyte based on a solvate ionic liquid for rechargeable
      flow batteries.
AB  - A redox-active supercooled liquid is obtained by forming a "solvate ionic liquid"
      from a mixture of a stabilized organic radical and a specific Li salt and
      stabilizing the mixture further below their melting points. As a catholyte, the
      addition of an appropriate amount of water helps to enhance the electrochemical
      advantage while maintaining its supercooled nature and the liquid shows a high
      energy density of 200 W h L(-1) with reversible charge/discharge. 

PMID- 25757723
TI  - Surrounding greenness, proximity to city parks and pregnancy outcomes in Kaunas
      cohort study.
AB  - There is increasing evidence that green space can improve the health and well
      being of urban residents. However, there has been no consistent evidence of the
      effect of city parks on reproductive health. We investigated whether surrounding
      greenness levels and/or distance to city parks affect birth outcomes. This study
      was based on 3292 singleton live-births from the Kaunas birth cohort, Lithuania
      (2007-2009), who were enrolled in the FP7 PHENOTYPE project study. Residential
      surrounding greenness level was ascertained as average of satellite-based
      normalized difference vegetation index (NDVI) within buffers of 100 m, 300 m, and
      500 m of each maternal home and distance to a city park was defined as distance
      to boundaries of the nearest city park. For each indicator of green space
      exposure, linear or logistic regression models were constructed to estimate
      change in birth outcomes adjusted for relevant covariates. An increase in
      distance to a city parks was associated with an increase in risk of preterm birth
      and decrease of gestational age. We found a statistically significant association
      between low surrounding greenness and term low birth weight. After assessing
      effect modification based on the low surrounding greenness (NDVI-500<median) and
      the distance to city parks (>1000 m), we found increased risks for low birth
      weight (OR 2.23, 1.20-4.15), term low birth weight (OR 2.97, 1.04-8.45) and
      preterm birth (OR 1.77, 1.10-2.81) for subjects with low surrounding greenness
      and farther distance from a park. Both higher surrounding greenness level and
      proximity to park have beneficial effects on pregnancy outcomes. A beneficial
      park effect on foetal growth is most apparent in the environment with low
      surrounding greenness level. Further investigation is needed to confirm this
      association.

PMID- 25757724
TI  - Recovery of Work-Related Stress: Complaint Reduction and Work-Resumption are
      Relatively Independent Processes.
AB  - PURPOSE: The process of recovery from work-related stress, consisting of
      complaint reduction and work-resumption, is not yet fully understood. The aim of
      this study was to investigate predictors of complaint reduction and work
      resumption, as well as testing complaint reduction as a mediator in the
      association between predictors and work-resumption. METHODS: Seventy-one patients
      on sickness-leave because of work-related stress complaints were followed over a
      period of 13 months. Predictors comprised personal (demographics, coping,
      cognitions), work-related (job-characteristics, social support), and illness
      related (complaint duration, absence duration) variables. Dependent variables
      were distress complaints, burnout complaints, and work-resumption. RESULTS:
      Complaints reduced considerably over time to borderline clinical levels and work
      resumption increased to 68% at 13 months. Predictors of stronger reduction of
      distress complaints were male gender, less working hours, less decision
      authority, more co-worker support, and shorter absence duration. Predictors of
      stronger reduction of burnout complaints were male gender, lower age, high
      education, less avoidant coping, less decision authority, more job security, and
      more co-worker support. Predictors of work-resumption were lower age and stronger
      reduction of burnout complaints. No indication for a mediating role of burnout
      complaints between the predictor age and work-resumption was found. CONCLUSIONS:
      Complaint reduction and work-resumption are relatively independent processes.
      Symptom reduction is influenced by individual and work-related characteristics,
      which holds promise for a multidisciplinary treatment approach for work-related
      stress.

PMID- 25757725
TI  - Effects of Modified Hatha Yoga in Industrial Rehabilitation on Physical Fitness
      and Stress of Injured Workers.
AB  - PURPOSE: The purpose of this study was to assess the effects of 8 weeks of
      modified hatha yoga training on physical fitness and stress level in injured
      workers. METHODS: Eighteen male and female injured workers, age between 18 and 55
      years, participated in this study. They were divided into two groups: an additive
      hatha yoga training to routine industrial rehabilitation program group (HYG: n =
      9) and a control group with no yoga training (CG: n = 9). A modified hatha yoga
      protocol was designed for this population by two certified yoga instructors,
      approved by a physical therapist, and conducted for 1 h, three times weekly for 8
      weeks. Physical fitness variables including flexibility of lower back and
      hamstrings, hand grip strength and lung capacity and scores of sensitivity to
      stress were evaluated at the time of recruitment and after 8 weeks of
      intervention. RESULTS: The values of all physical fitness variables and stress
      scores were no significant difference between the two groups at baseline.
      Significant post-yoga improvements for HYG group were noted in flexibility, hand
      grip strength, and vital capacity (p < 0.05). In contrast, there was no
      significant change in the CG group. Stress scores did not change as a result of
      hatha yoga training. CONCLUSION: An 8-week modified hatha yoga training
      experience exerted therapeutic effects on physical fitness variables including
      flexibility of lower back and hamstrings, hand grip strength and vital capacity,
      but not on stress level in injured workers. These findings indicate that hatha
      yoga can be a beneficial adjunct to routine physical therapy treatment in
      industrial rehabilitation programs.

PMID- 25757726
TI  - Dental extraction, immediate placement of dental implants, and immediate
      function.
AB  - Immediate function requires adequate implant stability. Immediate function
      requires prosthetic stability, particularly when multiple implants are loaded.
      Factors to consider for immediate implants into extraction sites are thickness of
      socket walls, thickness of gingival drape, optimal position of the implant, and
      patient factors such as hygiene and smoking cessation. 

PMID- 25757727
TI  - Toward continuous and scalable production of colloidal nanocrystals by switching
      from batch to droplet reactors.
AB  - Colloidal nanocrystals are finding widespread use in a wide variety of
      applications ranging from catalysis to photonics, electronics, energy
      harvesting/conversion/storage, environment protection, information storage, and
      biomedicine. Despite the large number of successful demonstrations, there still
      exists a significant gap between academic studies and industrial applications
      owing to the lack of an ability to produce colloidal nanocrystals in large
      quantities without losing control over their properties. Droplet reactors have
      shown great potential for the continuous and scalable production of colloidal
      nanocrystals with uniform and well-controlled sizes, shapes, structures, and
      compositions. In this tutorial review, we begin with rationales for the use of
      droplet reactors as a new platform to scale up the production of colloidal
      nanocrystals, followed by discussions of the general concepts and technical
      challenges in applying droplet reactors to the synthesis of nanocrystals,
      including droplet formation, introduction and mixing of reagents, management of
      gaseous species, and interfacial adsorption. At the end, we use a set of examples
      to highlight the unique capabilities of droplet reactors for the high-volume
      production of colloidal nanocrystals in the setting of both homogeneous
      nucleation and seed-mediated growth. 

PMID- 25757728
TI  - Easier said than done: ABO compatibility and D matching in apheresis platelet
      transfusions.
AB  - BACKGROUND: Many hospital transfusion services prioritize ABO plasma
      compatibility in platelet (PLT) transfusion to minimize risk for acute hemolytic
      transfusion reactions. In spite of the low risk of D alloimmunization associated
      with apheresis PLT transfusion, attempts may also be made to provide D- PLTs to D
      patients. This study was undertaken to assess how often ABO compatibility and/or
      D matching occurs at our institution and how the ABO and D mix of our PLT supply
      impacts PLT selection. STUDY DESIGN AND METHODS: We retrospectively reviewed the
      ABO and D type of all PLTs transfused plus the age, sex, and ABO and D type of
      all PLT recipients between January 2010 and March 2014 (51 months). RESULTS: We
      provided ABO-identical PLTs for 5281 (54.6%), ABO plasma-compatible and cellular
      incompatible for 3136 (32.4%), ABO low-titer plasma-incompatible and cellular
      compatible for 1150 (11.9%), ABO plasma-incompatible and cellular-compatible for
      30 (0.3%), and ABO plasma-incompatible and cellular-incompatible for 72 (0.7%).
      PLT supply did not match PLT demand based on patient ABO type, primarily due to a
      lower than expected supply of group O PLTs and higher than expected supply of
      group A and AB. D- patients were less likely to receive ABO-identical PLT
      transfusions (p = 0.0008), but were more likely to receive D- PLT transfusions (p
      < 0.0001). CONCLUSION: At our hospital, available inventory and PLT selection
      practices resulted in the majority of group O patients receiving cellular
      incompatible PLT transfusions. Efforts to provide D- PLTs to D- patients also
      resulted in fewer D- patients receiving ABO-identical PLT transfusions.

PMID- 25757729
TI  - Intercellular transfer along the trichomes of the invasive terminal heterocyst
      forming cyanobacterium Cylindrospermopsis raciborskii CS-505.
AB  - Cylindrospermopsis raciborskii CS-505 is an invasive freshwater filamentous
      cyanobacterium that when grown diazotrophically may develop trichomes of up to
      100 vegetative cells while differentiating only two end heterocysts, the sole
      sites for their N2-fixation process. We examined the diazotrophic growth and
      intercellular transfer mechanisms in C. raciborskii CS-505. Subjecting cultures
      to a combined-nitrogen-free medium to elicit N2 fixation, the trichome length
      remained unaffected while growth rates decreased. The structures and proteins for
      intercellular communication showed that while a continuous periplasmic space was
      apparent along the trichomes, the putative septal junction sepJ gene is divided
      into two open reading frames and lacks several transmembrane domains unlike the
      situation in Anabaena, differentiating a 5-fold higher frequency of heterocysts.
      FRAP analyses also showed that the dyes calcein and 5-CFDA were taken up by
      heterocysts and vegetative cells, and that the transfer from heterocysts and
      'terminal' vegetative cells showed considerably higher transfer rates than that
      from vegetative cells located in the middle of the trichomes. The data suggest
      that C. raciborskii CS-505 compensates its low-frequency heterocyst phenotype by
      a highly efficient transfer of the fixed nitrogen towards cells in distal parts
      of the trichomes (growing rapidly) while cells in central parts suffers (slow
      growth). 

PMID- 25757730
TI  - Comparison of DNA extraction protocols for the analysis of gut microbiota in
      fishes.
AB  - This study investigated the impacts of bacterial DNA extraction methodology on
      downstream analysis of fish gut microbiota. Feces and intestine samples were
      taken from three sympatric freshwater fish species with varying diets. Samples
      were processed immediately (approximately 4 h after capture; fresh), stored at 
      20  degrees C for 15 days or preserved in RNAlater(r) reagent for 15 days. DNA
      was then extracted using two commercial kits: one designed for animal tissues and
      one specifically formulated for stool samples. Microbial community fingerprints
      were generated using ribosomal intergenic spacer analysis. Factors including
      diversity as depicted by band number, band intensity, repeatability and
      practicalities such as cost and time were considered. Despite significant
      differences in microbiota structure, results were similar between feces and
      intestine samples. Frozen samples were consistently outperformed by other storage
      methods and the stool kit typically outperformed the tissue kit. Overall, we
      recommend extraction of bacterial DNA from fresh samples using the stool kit for
      both sample types. If samples cannot be processed immediately, preservation in
      RNAlater(r) is preferred to freezing. Choice of DNA extraction method
      significantly influences the results of downstream microbial community analysis
      and thus should be taken into consideration for metadata analysis.

PMID- 25757731
TI  - Rescue of fish exposed to a lethal dose of pathogen, by signals from sublethally
      exposed survivors.
AB  - Rainbow trout (Oncorhynchus mykiss, Walbaum) were challenged intraperitoneally
      with a sublethal dose of Vibrio anguillarum VIB1 and allowed to recover. Then,
      after 7 days, naive fish, (designated as 'bystander' fish) which had never been
      exposed to the pathogen, were introduced to the same tank. These swam with the
      adapted (recovered) fish for 7 days before both groups and a control (never
      exposed directly to the pathogen or to recovered fish) group were exposed to a
      lethal dose of VIB1. Mortality records were 100% in the control group within 3
      days, 47% in the adapted group and 60% in the unchallenged bystander group, which
      swam with the adapted group. In both the latter groups, the time to death of the
      non-surviving fish was attenuated. This inter-animal communication of signals has
      previously been documented for animals exposed to ionizing radiation. Assays of
      tissues from control, challenged and 'bystander fish exposed to the pathogen
      showed that a signal as yet unidentified but similar to that seen in bystanders
      to irradiated fish was being produced. This signal caused a sharp and transient
      increase in intracellular calcium and a decrease in clonogenicity in a well
      characterized reporter assay. 

PMID- 25757732
TI  - Factors influencing maternal distress among Dutch women with a healthy pregnancy.
AB  - BACKGROUND: Maternal distress is a public health concern. Assessment of emotional
      wellbeing is not integrated in Dutch antenatal care. Midwives need to understand
      the influencing factors in order to identify women who are more vulnerable to
      experience maternal distress. OBJECTIVE: To examine levels of maternal distress
      during pregnancy and to determine the relationship between maternal distress and
      aetiological factors. METHODS: A cross-sectional study including 458 Dutch
      speaking women with uncomplicated pregnancies during all trimesters of pregnancy.
      Data were collected with questionnaires between 10 September and 6 November 2012.
      Demographic characteristics and personal details were obtained. Maternal distress
      was measured with the Edinburgh Depression Scale (EDS), State-Trait Anxiety
      Inventory (STAI), and Pregnancy-Related Anxiety Questionnaire (PRAQ). Behaviour
      was measured with Coping Operations Preference Enquiry-Easy (COPE-Easy).
      Descriptive statistics and multiple linear regression analysis were used.
      RESULTS: Just over 20 percent of the women in our sample (21.8%) had a heightened
      score on one or more of the EDS, STAI or PRAQ. History of psychological problems
      (B=1.071; p=.001), having young children (B=2.998; p=.001), daily stressors
      (B=1.304; p=<.001), avoidant coping (B=1.047, p=<.001), somatisation (B=.484;
      p=.004), and negative feelings towards the forthcoming birth (B=.636; p=<.001)
      showed a significant positive relationship with maternal distress. Self
      disclosure (B=-.863; p=.004) and acceptance of the situation (B=-.542; p=.008)
      showed a significant negative relationship with maternal distress. CONCLUSION:
      Maternal distress occurs among women with a healthy pregnancy and is
      significantly influenced by a variety of factors. Midwives need to recognise the
      factors that make women more vulnerable to develop and experience maternal
      distress in order to give adequate advice about how to best cope with this
      condition.

PMID- 25757735
TI  - Medication absorption for patients with an ileostomy.
AB  - The Association of Stoma Care Nurses UK (2013) has stressed that it is the role
      of the stoma care nurse to provide education to patients, carers, prescribers and
      other nurses. This includes the area of medication management. Ensuring patients
      with an ileostomy receive their medication in a form they can absorb is of
      importance to every stoma care nurse. Prescribing for patients with a stoma calls
      for special care. Each patient with an ileostomy requires assessment of their
      medication regimen for the purpose of identifying potential medical absorption
      issues. However, from an extensive literature search, it is evident that there is
      very little literature published on this subject. This article looks at the
      considerations to take into account when prescribing medication for ileostomy
      patients, and examines the results of a clinical audit on medication prescribers'
      knowledge of the impact of ileostomy formation on the absorption of medication. 

PMID- 25757734
TI  - Lobular breast cancer: molecular basis, mouse and cellular models.
AB  - Infiltrating lobular breast cancer (ILC) is the most common special breast cancer
      subtype. With mutational or epigenetic inactivation of the cell adhesion molecule
      E-cadherin (CDH1) being confined almost exclusively to ILC, this tumor entity
      stands out from all other types of breast cancers. The molecular basis of ILC is
      linked to loss of E-cadherin, as evidenced by human CDH1 germline mutations and
      conditional knockout mouse models. A better understanding of ILC beyond the level
      of descriptive studies depends on physiologically relevant and functional tools.
      This review provides a detailed overview on ILC models, including well
      characterized cell lines, xenograft tumors and genetically engineered mouse
      models. We consider advantages and limitations of these models and evaluate their
      representativeness for human ILC. The still incompletely defined mechanisms by
      which loss of E-cadherin drives malignant transformation are discussed based on
      recent findings in these models. Moreover, candidate genes and signaling pathways
      potentially involved in ILC development and progression as well as anticancer
      drug and endocrine resistance are highlighted. 

PMID- 25757736
TI  - A stoma care nurse specialist.

PMID- 25757733
TI  - Telephone, print, and Web-based interventions for physical activity, diet, and
      weight control among cancer survivors: a systematic review.
AB  - PURPOSE: Broad-reach (non-face-to-face) modalities offer an accessible and cost
      effective means to provide behavior change programs in diverse and growing cancer
      survivor populations. The purpose of this systematic review is to evaluate the
      efficacy of physical activity, dietary, and/or weight control interventions for
      cancer survivors in which telephone, short-message service, print, and/or Web is
      the primary method of delivery. METHODS: A structured search of PubMed, Embase,
      Web of Science, CINAHL, and CENTRAL (May 2013) was conducted. Included studies
      focused and reported on physical activity (PA) and dietary change and/or weight
      control in adult cancer survivors, delivered at least 50% of intervention
      contacts by broad-reach modality and included a control group. Study design,
      intervention features, and behavioral/weight outcomes were extracted, tabulated,
      and summarized. RESULTS: Twenty-seven studies were included; 22 telephone, three
      Web, and two print. Sixteen studies targeted PA, two diet, and nine targeted
      multiple behaviors. Most studies (18/27) targeted a single survivor group, namely
      breast cancer (n = 12). Nineteen of 27 studies found evidence for initiation of
      behavior change, with only eight reporting on maintenance and one on cost
      effectiveness. CONCLUSIONS: This review provides support for broad-reach
      modalities, particularly the telephone, in the delivery of lifestyle
      interventions to cancer survivors. Future research should evaluate (1) newer
      technologies (i.e., SMS and mobile phone applications), (2) interventions for
      diverse cancer survivors and those targeting multiple behaviors, (3) long-term
      outcomes, and 4) cost-effectiveness. IMPLICATIONS FOR CANCER SURVIVORS: Broad
      reach lifestyle interventions are effective, with further research needed to
      evaluate their generalizability and integration into cancer care.

PMID- 25757737
TI  - Use of barrier creams for sore skin.

PMID- 25757738
TI  - Patient perspectives of silicone technology in stoma care.

PMID- 25757739
TI  - Association of Stoma Care Nurses strives for excellence.

PMID- 25757740
TI  - Incorporating the Principles of Nursing Practice and the 6Cs.
AB  - This article will demonstrate how the Royal College of Nursing's (RCN's)
      Principles of Nursing Practice (2010) and the 6Cs (Cummings and Bennett, 2012a ;
      2012b) can be applied to stoma care nursing. The multidimensional role of the
      stoma care nurse means that he or she is well placed to improve quality and
      standards in stoma nursing care. Stoma care nurses provide direct patient care
      and can play a vital part in helping patients with a stoma, a long-term
      condition, ensuring that their patients get the best possible care (RCN, 2010).
      The poster contained within this article was displayed at the Association of
      Stoma Care Nurses (ASCN) national conference in Harrogate in October 2014 and was
      voted the overall winner. The authors of the article and the poster are stoma
      care nurses working in the acute and community settings and, between 2013 and
      2014, they completed the RCN's Clinical Leadership Programme (RCN, 2005). The NHS
      Plan (Department of Health, 2000) identified the importance of leadership and the
      necessity of remodelling the NHS around the needs of service users. With this in
      mind, using the Principles of Nursing Practice and the 6Cs within stoma care
      demonstrates development with a consistent focus on patient care.

PMID- 25757742
TI  - (Intra)cellular stability of inorganic nanoparticles: effects on cytotoxicity,
      particle functionality, and biomedical applications.

PMID- 25757741
TI  - The Arabidopsis PLAT domain protein1 promotes abiotic stress tolerance and growth
      in tobacco.
AB  - Plant growth and consequently crop yield can be severely compromised by abiotic
      and biotic stress conditions. Transgenic approaches that resulted in increased
      tolerance against abiotic stresses often were typically accompanied by adverse
      effects on plant growth and fitness under optimal growing conditions. Proteins
      that belong to the PLAT-plant-stress protein family harbour a single PLAT
      (Polycystin, Lipoxygenase, Alpha-toxin and Triacylglycerol lipase) domain and are
      ubiquitously present in monocot and dicot plant species. Until now, only limited
      data is available for PLAT-plant-stress family members, which suggested that
      these proteins in general could promote tolerance towards stress responses. We
      studied the function of the Arabidopsis PLAT-plant-stress protein AtPLAT1
      employing heterologous gain-of-function analysis in tobacco. AtPLAT1 conferred
      increased abiotic stress tolerance in tobacco, evident by improved tolerance
      towards cold, drought and salt stresses, and promoted growth, reflected by a
      faster development under non-stressed conditions. However, the overexpression of
      AtPLAT1 in tobacco reduced the tolerance towards biotic stress conditions and,
      therefore, could be involved in regulating the crosstalk between abiotic and
      biotic stress responses. Thus, we showed that heterologously expressed AtPLAT1
      functions as positive regulator of abiotic stress tolerance and plant growth,
      which could be an important new asset for strategies to develop plants with
      improved abiotic stress tolerance, without growth and subsequent yield penalties
      under optimal growth conditions. 

PMID- 25757743
TI  - Mobile dune fixation by a fast-growing clonal plant: a full life-cycle analysis.
AB  - Desertification is a global environmental problem, and arid dunes with sparse
      vegetation are especially vulnerable to desertification. One way to combat
      desertification is to increase vegetation cover by planting plant species that
      can realize fast population expansion, even in harsh environments. To evaluate
      the success of planted species and provide guidance for selecting proper species
      to stabilize active dunes, demographic studies in natural habitats are essential.
      We studied the life history traits and population dynamics of a dominant clonal
      shrub Hedysarum laeve in Inner-Mongolia, northern China. Vital rates of 19057
      ramets were recorded during three annual censuses (2007-2009) and used to
      parameterize Integral Projection Models to analyse population dynamics. The life
      history of H. laeve was characterized by high ramet turnover and population
      recruitment entirely depended on clonal propagation. Stochastic population growth
      rate was 1.32, suggesting that the populations were experiencing rapid expansion.
      Elasticity analysis revealed that clonal propagation was the key contributor to
      population growth. The capacity of high clonal propagation and rapid population
      expansion in mobile dunes makes H. laeve a suitable species to combat
      desertification. Species with similar life-history traits to H. laeve are likely
      to offer good opportunities for stabilizing active dunes in arid inland
      ecosystems. 

PMID- 25757744
TI  - Mef2d is essential for the maturation and integrity of retinal photoreceptor and
      bipolar cells.
AB  - Mef2 transcription factors play a crucial role in cardiac and skeletal muscle
      differentiation. We found that Mef2d is highly expressed in the mouse retina and
      its loss causes photoreceptor degeneration similar to that observed in human
      retinitis pigmentosa patients. Electroretinograms (ERGs) were severely impaired
      in Mef2d-/- mice. Immunohistochemistry showed that photoreceptor and bipolar cell
      synapse protein levels severely decreased in the Mef2d-/- retina. Expression
      profiling by microarray analysis showed that Mef2d is required for the expression
      of various genes in photoreceptor and bipolar cells, including cone arrestin,
      Guca1b, Pde6h and Cacna1s, which encode outer segment and synapse proteins. We
      also observed that Mef2d synergistically activates the cone arrestin (Arr3)
      promoter with Crx, suggesting that functional cooperation between Mef2d and Crx
      is important for photoreceptor cell gene regulation. Taken together, our results
      show that Mef2d is essential for photoreceptor and bipolar cell gene expression,
      either independently or cooperatively with Crx.

PMID- 25757745
TI  - Factors affecting immunoreactivity in long-term storage of formalin-fixed
      paraffin-embedded tissue sections.
AB  - Antigen decay in archival formalin-fixed paraffin-embedded (FFPE) tissue sections
      for immunohistochemistry is a well-known phenomenon which may have repercussions
      on translational and research studies and length of storage time appears
      fundamental. The aim of this study was to evaluate all possible factors which may
      lead to antigen decay on a prospective standardized collection of human tissues
      with a panel of 14 routinely used antibodies. Serial slide sections from FFPE
      control tissues were stored using different methods (routine storage at room
      temperature, Parafilm((r)) protected, paraffin coated and cold stored at 4 
      degrees C) and for different time periods: 1, 6, 9, 12, 24 and 36 months.
      Immunohistochemistry was performed at each time cutoff simultaneously on stored
      sections and on freshly cut sections using a panel of 14 antibodies.
      Immunoreactivity was compared with immunoreactions performed at time zero.
      Reduction in immunostaining was observed for a subset of antibodies (CD3, CD 31,
      CD117, estrogen and progesterone receptors, Ki67, p53, TTF-1, vimentin) while for
      others (smooth muscle actin, keratins 7, 20, AE1/AE3, 34betaE12), no antigen
      decay was observed. Loss of antigenicity was proportional to tissue section age
      and was dependent on mode of storage with cold storage slides being the least
      affected. All antigens with reductions in immunosignal were nuclear or
      membranous, and they all required heat pre-treatment for antigen retrieval. In
      contrast to results from other studies, when pre-analytical factors are strictly
      controlled and standardized, antigen decay seems to be restricted to nuclear or
      membrane antigens which require heat antigen retrieval.

PMID- 25757746
TI  - Highly bright yellow-green-emitting CuInS2 colloidal quantum dots with
      core/shell/shell architecture for white light-emitting diodes.
AB  - In this study, we report bright yellow-green-emitting CuInS2 (CIS)-based quantum
      dots (QDs) and two-band white light-emitting diodes (LEDs) using them. To achieve
      high quantum efficiency (QE) of yellow-green-emitting CIS QDs, core/shell/shell
      strategy was introduced to high quality CIS cores (QE = 31.7%) synthesized by
      using metal-oleate precursors and 1-dodecanethiol. The CIS/ZnS/ZnS QDs showed a
      high QE of 80.0% and a peak wavelength of 559 nm under the excitation of 450 nm,
      which is well matched with dominant wavelength of blue LEDs. The formation of
      core/shell/shell structure was confirmed by X-ray diffraction, transmission
      electron microscopy, and inductively coupled plasma-optical emission spectroscopy
      analyses. Intense and broad yellow-green emission band of the CIS/ZnS/ZnS is
      beneficial for bright two-band white light. When the CIS/ZnS/ZnS was coated on
      the blue LEDs, the fabricated white LED showed bright natural white light
      (luminous efficacy (eta(L)) = 80.3 lm.W(-1), color rendering index (R(a)) = 73,
      correlated color temperature (T(c)) = 6140 K). The QD-white LED package showed a
      high light conversion efficiency of 72.6%. In addition, the CIS/ZnS/ZnS-converted
      white LED showed relatively stable white light against the variation of forward
      bias currents of 20-150 mA [color coordinates (x, y) = (0.3320-0.3207, 0.2997
      0.2867), R(a) = 70-72, T(c) = 5497-6375 K].

PMID- 25757747
TI  - Proteomic insights into synthesis of isoflavonoids in soybean seeds.
AB  - Soybean seeds are the major human dietary source of isoflavonoids, a class of
      plant natural products almost entirely exclusive to legumes. Isoflavonoids reduce
      the risk of a number of chronic human illnesses. Biosynthesis and accumulation of
      this class of compounds is a multigenic and complex trait, with a great deal of
      variability among soybean cultivars and with respect to the environment. There is
      a wealth of genomic, transcriptomic, and metabolomics data regarding isoflavonoid
      biosynthesis, but the connection between multigene families and their cognate
      proteins is a missing link that could provide us with a great deal of functional
      information. The changing proteome of the developing seed can shed light on the
      correlative increase in isoflavonoids, while the maternal seed coat proteome can
      provide the link with inherited metabolic and signaling machinery. In this
      effort, 'seed-filling' proteomics has revealed key secondary metabolite enzymes
      that quantitatively vary throughout seed development. Seed coat proteomics has
      revealed the existence of metabolic apparatus specific to isoflavonoid
      biosynthesis (isoflavonoid reductase) that could potentially influence the
      chemical content of this organ. The future of proteomic analysis of isoflavonoid
      biosynthesis should be centered on the development of quantitative, tissue
      specific proteomes that emphasize low-abundance metabolic proteins to extract the
      whole suite of factors involved. 

PMID- 25757748
TI  - Striatal blood-brain barrier permeability in Parkinson's disease.
AB  - In vivo studies have shown that blood-brain barrier (BBB) dysfunction is involved
      in the course of Parkinson's disease (PD). However, these have lacked either
      anatomic definition or the ability to recognize minute changes in BBB integrity.
      Here, using histologic markers of serum protein, iron, and erythrocyte
      extravasation, we have shown significantly increased permeability of the BBB in
      the postcommissural putamen of PD patients. The dense innervation of the striatum
      by PD-affected regions allows for exploitation of this permeability for
      therapeutic goals. These results are also discussed in the context of the
      retrograde trans-synaptic hypothesis of PD spread. 

PMID- 25757749
TI  - Reliability of CT perfusion-derived CBF in relation to hemodynamic compromise in
      patients with cerebrovascular steno-occlusive disease: a comparative study with
      15O PET.
AB  - In the bolus tracking technique with computed tomography (CT) or magnetic
      resonance imaging, cerebral blood flow (CBF) is computed from deconvolution
      analysis, but its accuracy is unclear. To evaluate the reliability of CT
      perfusion (CTP)-derived CBF, we examined 27 patients with symptomatic or
      asymptomatic unilateral cerebrovascular steno-occlusive disease. Results from
      three deconvolution algorithms, standard singular value decomposition (sSVD),
      delay-corrected SVD (dSVD), and block-circulant SVD (cSVD), were compared with
      (15)O positron emission tomography (PET) as a reference standard. To investigate
      CBF errors associated with the deconvolution analysis, differences in lesion-to
      normal CBF ratios between PET and CTP were correlated with prolongation of
      arterial-tissue delay (ATD) and mean transit time (MTT) in the lesion hemisphere.
      Computed tomography perfusion results strongly depended on the deconvolution
      algorithms used. Standard singular value decomposition showed ATD-dependent
      underestimation of CBF ratio, whereas cSVD showed overestimation of the CBF ratio
      when MTT was severely prolonged in the lesions. The computer simulations
      reproduced the trend observed in patients. Deconvolution by dSVD can provide
      lesion-to-normal CBF ratios less dependent on ATD and MTT, but requires accurate
      ATD maps in advance. A practical and accurate method for CTP is required to
      assess CBF in patients with MTT-prolonged regions. 

PMID- 25757750
TI  - Preconditioning cortical lesions reduce the incidence of peri-infarct
      depolarizations during focal ischemia in the Spontaneously Hypertensive Rat:
      interaction with prior anesthesia and the impact of hyperglycemia.
AB  - The relationship between peri-infarct depolarizations (PIDs) and infarction was
      investigated in a model of preconditioning by cortical freeze lesions (cryogenic
      lesions, CL) in the Spontaneously Hypertensive Rat. Small (< 5 mm(3)) lesions
      produced 24 hours before permanent focal ischemia were protective, without
      impacting baseline cerebral blood flow (CBF) and metabolism. Prior CL reduced
      infarct volume, associated with improved penumbral CBF as previously showed for
      ischemic preconditioning. The brief initial procedure avoided sham effects on
      infarct volume after subsequent occlusion under brief anesthesia. However, under
      prolonged isoflurane anesthesia for perfusion monitoring both sham and CL rats
      showed reduced PID incidence relative to naive animals. This anesthesia effect
      could be eliminated by using alpha-chloralose during perfusion imaging. As an
      additional methodological concern, blood glucose was frequently elevated at the
      time of the second surgery, reflecting buprenorphine-induced pica and other
      undefined mechanisms. Even modest hyperglycemia (>10 mmol/L) reduced PID
      incidence. In normoglycemic animals CL preconditioning reduced PID number by 50%,
      demonstrating associated effects on PID incidence, penumbral perfusion, and
      infarct progression. Hyperglycemia suppressed PIDs without affecting the
      relationship between CBF and infarction. This suggests that the primary effect of
      preconditioning is to improve penumbral perfusion, which in turn impacts PID
      incidence and infarct size.

PMID- 25757751
TI  - Dexamethasone potentiates in vitro blood-brain barrier recovery after primary
      blast injury by glucocorticoid receptor-mediated upregulation of ZO-1 tight
      junction protein.
AB  - Owing to the frequent incidence of blast-induced traumatic brain injury (bTBI) in
      recent military conflicts, there is an urgent need to develop effective therapies
      for bTBI-related pathologies. Blood-brain barrier (BBB) breakdown has been
      reported to occur after primary blast exposure, making restoration of BBB
      function and integrity a promising therapeutic target. We tested the hypothesis
      that treatment with dexamethasone (DEX) after primary blast injury potentiates
      recovery of an in vitro BBB model consisting of mouse brain endothelial cells
      (bEnd.3). DEX treatment resulted in complete recovery of transendothelial
      electrical resistance and hydraulic conductivity 1 day after injury, compared
      with 3 days for vehicle-treated injured cultures. Administration of RU486
      (mifepristone) inhibited effects of DEX, confirming that barrier restoration was
      mediated by glucocorticoid receptor signaling. Potentiated recovery with DEX
      treatment was accompanied by stronger zonula occludens (ZO)-1 tight junction
      immunostaining and expression, suggesting that increased ZO-1 expression was a
      structural correlate to BBB recovery after blast. Interestingly, augmented ZO-1
      protein expression was associated with specific upregulation of the alpha(+)
      isoform but not the alpha(-) isoform. This is the first study to provide a
      mechanistic basis for potentiated functional recovery of an in vitro BBB model
      because of glucocorticoid treatment after primary blast injury. 

PMID- 25757752
TI  - Combined ampakine and BDNF treatments enhance poststroke functional recovery in
      aged mice via AKT-CREB signaling.
AB  - Cerebral ischemia results in damage to neuronal circuits and lasting impairment
      in function. We have previously reported that stimulation of alpha-amino-3
      hydroxy-5-methyl-4-isoxazolepropionic acid receptors with the ampakine, CX1837,
      increases brain-derived neurotrophic factor (BDNF) levels and affords significant
      motor recovery after stroke in young mice. Here, we investigated whether
      administration of CX1837 in aged (24 months old) mice was equally effective. In a
      model of focal ischemia, administration of CX1837 from 5 days after stroke
      resulted in a small gain of motor function by week 6 after stroke. Mice that
      received a local delivery of BDNF via hydrogel implanted into the stroke cavity
      also showed a small gain of function from 4 to 6 weeks after stroke. Combining
      both treatments, however, resulted in a marked improvement in motor function from
      2 weeks after insult. Assessment of peri-infarct tissue 2 weeks after stroke
      revealed a significant increase in p-AKT and p-CREB after the combined drug
      treatment. Using the pan-AKT inhibitor, GSK-690693, or deletion of CREB from
      forebrain neurons using the CREB-flox/CAMKii-cre mice, we were able to block the
      recovery of motor function. These data suggest that combined CX1837 and local
      delivery of BDNF are required to achieve maximal functional recovery after stroke
      in aged mice, and is occurring via the AKT-GSK3-CREB signaling pathway. 

PMID- 25757753
TI  - Enhanced parenchymal arteriole tone and astrocyte signaling protect neurovascular
      coupling mediated parenchymal arteriole vasodilation in the spontaneously
      hypertensive rat.
AB  - Functional hyperemia is the regional increase in cerebral blood flow upon
      increases in neuronal activity which ensures that the metabolic demands of the
      neurons are met. Hypertension is known to impair the hyperemic response; however,
      the neurovascular coupling mechanisms by which this cerebrovascular dysfunction
      occurs have yet to be fully elucidated. To determine whether altered cortical
      parenchymal arteriole function or astrocyte signaling contribute to blunted
      neurovascular coupling in hypertension, we measured parenchymal arteriole
      reactivity and vascular smooth muscle cell Ca(2+) dynamics in cortical brain
      slices from normotensive Wistar Kyoto (WKY) and spontaneously hypertensive (SHR)
      rats. We found that vasoconstriction in response to the thromboxane A2 receptor
      agonist U46619 and basal vascular smooth muscle cell Ca(2+) oscillation frequency
      were significantly increased in parenchymal arterioles from SHR. In perfused and
      pressurized parenchymal arterioles, myogenic tone was significantly increased in
      SHR. Although K(+)-induced parenchymal arteriole dilations were similar in WKY
      and SHR, metabotropic glutamate receptor activation-induced parenchymal arteriole
      dilations were enhanced in SHR. Further, neuronal stimulation-evoked parenchymal
      arteriole dilations were similar in SHR and WKY. Our data indicate that
      neurovascular coupling is not impaired in SHR, at least at the level of the
      parenchymal arterioles. 

PMID- 25757754
TI  - One-year high fat diet affects muscle-but not brain mitochondria.
AB  - It is well known that few weeks of high fat (HF) diet may induce metabolic
      disturbances and mitochondrial dysfunction in skeletal muscle. However, little is
      known about the effects of long-term HF exposure and effects on brain
      mitochondria are unknown. Wistar rats were fed either chow (13E% fat) or HF diet
      (60E% fat) for 1 year. The HF animals developed obesity, dyslipidemia, insulin
      resistance, and dysfunction of isolated skeletal muscle mitochondria: state 3 and
      state 4 were 30% to 50% increased (P<0.058) with palmitoyl carnitine (PC), while
      there was no effect with pyruvate as substrate. Adding also succinate in state 3
      resulted in a higher substrate control ratio (SCR) with PC, but a lower SCR with
      pyruvate (P<0.05). The P/O2 ratio was lower with PC (P<0.004). However, similar
      tests on isolated brain mitochondria from the same animal showed no changes with
      the substrates relevant for brain (pyruvate and 3-hydroxybutyrate). Thus, long
      term HF diet was associated with obesity, dyslipidemia, insulin resistance, and
      significantly altered mitochondrial function in skeletal muscle. Yet, brain
      mitochondria were unaffected. We suggest that the relative isolation of the brain
      due to the blood-brain barrier may play a role in this strikingly different
      phenotype of mitochondria from the two tissues of the same animal. 

PMID- 25757755
TI  - Mild hypothermia inhibits systemic and cerebral complement activation in a swine
      model of cardiac arrest.
AB  - Complement activation has been implicated in ischemia/reperfusion injury. This
      study aimed to determine whether mild hypothermia (HT) inhibits systemic and
      cerebral complement activation after resuscitation from cardiac arrest. Sixteen
      minipigs resuscitated from 8 minutes of untreated ventricular fibrillation were
      randomized into two groups: HT group (n=8), treated with HT (33 degrees C) for 12
      hours; and normothermia group (n=8), treated similarly as HT group except for
      cooling. Blood samples were collected at baseline and 0.5, 6, 12, and 24 hours
      after return of spontaneous circulation (ROSC). The brain cortex was harvested 24
      hours after ROSC. Complement and pro-inflammatory markers were detected using
      enzyme-linked immunosorbent assay. Neurologic deficit scores were evaluated 24
      hours after ROSC. C1q, Bb, mannose-binding lectin (MBL), C3b, C3a, C5a,
      interleukin-6, and tumor necrosis factor-alpha levels were significantly
      increased under normothermia within 24 hours after ROSC. However, these increases
      were significantly reduced by HT. Hypothermia decreased brain C1q, MBL, C3b, and
      C5a contents 24 hours after ROSC. Hypothermic pigs had a better neurologic
      outcome than normothermic pigs. In conclusion, complement is activated through
      classic, alternative, and MBL pathways after ROSC. Hypothermia inhibits systemic
      and cerebral complement activation, which may provide an additional mechanism of
      cerebral protection.

PMID- 25757756
TI  - Accelerated pericyte degeneration and blood-brain barrier breakdown in
      apolipoprotein E4 carriers with Alzheimer's disease.
AB  - The blood-brain barrier (BBB) limits the entry of neurotoxic blood-derived
      products and cells into the brain that is required for normal neuronal
      functioning and information processing. Pericytes maintain the integrity of the
      BBB and degenerate in Alzheimer's disease (AD). The BBB is damaged in AD,
      particularly in individuals carrying apolipoprotein E4 (APOE4) gene, which is a
      major genetic risk factor for late-onset AD. The mechanisms underlying the BBB
      breakdown in AD remain, however, elusive. Here, we show accelerated pericyte
      degeneration in AD APOE4 carriers >AD APOE3 carriers >non-AD controls, which
      correlates with the magnitude of BBB breakdown to immunoglobulin G and fibrin. We
      also show accumulation of the proinflammatory cytokine cyclophilin A (CypA) and
      matrix metalloproteinase-9 (MMP-9) in pericytes and endothelial cells in AD
      (APOE4 >APOE3), previously shown to lead to BBB breakdown in transgenic APOE4
      mice. The levels of the apoE lipoprotein receptor, low-density lipoprotein
      receptor-related protein-1 (LRP1), were similarly reduced in AD APOE4 and APOE3
      carriers. Our data suggest that APOE4 leads to accelerated pericyte loss and
      enhanced activation of LRP1-dependent CypA-MMP-9 BBB-degrading pathway in
      pericytes and endothelial cells, which can mediate a greater BBB damage in AD
      APOE4 compared with AD APOE3 carriers.

PMID- 25757757
TI  - Perihematoma cerebral blood flow is unaffected by statin use in acute
      intracerebral hemorrhage patients.
AB  - Statin therapy has been associated with improved cerebral blood flow (CBF) and
      decreased perihematoma edema in animal models of intracerebral hemorrhage (ICH).
      We aimed to assess the relationship between statin use and cerebral hemodynamics
      in ICH patients. A post hoc analysis of 73 ICH patients enrolled in the
      Intracerebral Hemorrhage Acutely Decreasing Arterial Pressure Trial (ICH ADAPT).
      Patients presenting <24 hours from ICH onset were randomized to a systolic blood
      pressure target <150 or <180 mm Hg with computed tomography perfusion imaging 2
      hours after randomization. Cerebral blood flow maps were calculated. Hematoma and
      edema volumes were measured planimetrically. Regression models were used to
      assess the relationship between statin use, perihematoma edema and cerebral
      hemodynamics. Fourteen patients (19%) were taking statins at the time of ICH.
      Statin-treated patients had similar median (IQR Q25 to 75) hematoma volumes (21.1
      (9.5 to 38.3) mL versus 14.5 (5.6 to 27.7) mL, P=0.25), but larger median (IQR
      Q25 to 75) perihematoma edema volumes (2.9 (1.7 to 9.0) mL versus 2.2 (0.8 to
      3.5) mL, P=0.02) compared with nontreated patients. Perihematoma and ipsilateral
      hemispheric CBF were similar in both groups. A multivariate linear regression
      model revealed that statin use and hematoma volumes were independent predictors
      of acute edema volumes. Statin use does not affect CBF in ICH patients. Statin
      use, along with hematoma volume, are independently associated with increased
      perihematoma edema volume.

PMID- 25757759
TI  - Sutureless prostheses and less invasive aortic valve replacement: just an issue
      of clamping time?
AB  - BACKGROUND: Recently, sutureless aortic bioprostheses have been increasingly
      adopted to facilitate minimally invasive aortic valve replacement. We aimed at
      evaluating the impact of the transition from conventional bioprostheses to the
      routine use of the 3f Enable prosthesis (Medtronic ATS Medical, Minneapolis, MN)
      for aortic valve replacement through ministernotomy. METHODS: Between November
      2009 and November 2012, 83 consecutive minimally invasive aortic valve
      replacement procedures were performed in our institution by the same surgeon
      through an upper T-shaped ministernotomy. The earliest 42 patients (group A)
      received a conventional bioprosthesis, and the later 41 patients (group B)
      received the sutureless 3f Enable valve. Aortic clamping and cardiopulmonary
      bypass times, early outcomes, and valve hemodynamics were compared. RESULTS:
      There was no statistical intergroup difference in baseline characteristics. In
      hospital mortality was 1% (a single nonvalve-related death). Average aortic
      clamping times in group A and group B were, respectively, 85 +/- 17 and 47 +/- 11
      minutes (p < 0.0001); the cardiopulmonary bypass time was 108 +/- 21 and 69 +/-
      15 minutes, respectively (p < 0.0001). There were three paravalvular leakages in
      group A (grade I) and four in group B (two grade I, and two grade II); three
      pacemaker implantations occurred in group B (p = 0.07); mean transvalvular
      gradient at discharge was 16.9 +/- 9.1 mm Hg in group A and 11.4 +/- 4.3 mm Hg in
      group B (p = 0.0007). During follow-up (average 25.5 +/- 12.9 months), one
      structural valve deterioration was registered in group A, and was treated with a
      valve-in-valve procedure. CONCLUSIONS: In our initial experience, the sutureless
      3f Enable technology significantly reduced the clamping and cardiopulmonary
      bypass times, as well as the mean transvalvular gradient in aortic valve
      replacement through ministernotomy.

PMID- 25757758
TI  - Angiotensin-(1-7) protects against the development of aneurysmal subarachnoid
      hemorrhage in mice.
AB  - Angiotensin-(1-7) (Ang-(1-7)) can regulate vascular inflammation and remodeling,
      which are processes that have important roles in the pathophysiology of
      intracranial aneurysms. In this study, we assessed the effects of Ang-(1-7) in
      the development of intracranial aneurysm rupture using a mouse model of
      intracranial aneurysms in which aneurysmal rupture (i.e., aneurysmal subarachnoid
      hemorrhage) occurs spontaneously and causes neurologic symptoms. Treatment with
      Ang-(1-7) (0.5 mg/kg/day), Mas receptor antagonist (A779 0.5 mg/kg/day or 2.5
      mg/kg/day), or angiotensin II type 2 receptor (AT2R) antagonist (PD 123319, 10
      mg/kg/day) was started 6 days after aneurysm induction and continued for 2 weeks.
      Angiotensin-(1-7) significantly reduced the rupture rate of intracranial
      aneurysms without affecting the overall incidence of aneurysms. The protective
      effect of Ang-(1-7) was blocked by the AT2R antagonist, but not by the Mas
      receptor antagonist. In AT2R knockout mice, the protective effect of Ang-(1-7)
      was absent. While AT2R mRNA was abundantly expressed in the cerebral arteries and
      aneurysms, Mas receptor mRNA expression was very scarce in these tissues.
      Angiotensin-(1-7) reduced the expression of tumor necrosis factor-alpha and
      interleukin-1beta in cerebral arteries. These findings indicate that Ang-(1-7)
      can protect against the development of aneurysmal rupture in an AT2R-dependent
      manner.

PMID- 25757760
TI  - Red blood cells and mortality after coronary artery bypass graft surgery: an
      analysis of 672 operative deaths.
AB  - BACKGROUND: Prior studies have implicated transfusion as a risk factor for
      mortality in coronary artery bypass graft surgery (CABG). To further our
      understanding of the true association between transfusion and outcome, we
      specifically analyzed the subgroup of patients who died after undergoing CABG.
      METHODS: A total of 34,362 patients underwent isolated CABG between January 2008
      and September 2013 and were entered into a statewide collaborative database; 672
      patients (2.0%) died and form the basis for this study. Univariate analysis
      compared preoperative and intraoperative variables, as well as postoperative
      outcomes, between those with and without transfusion in both unadjusted cohorts
      and those matched by predicted risk of mortality (PROM). Mortality was further
      evaluated with phase of care analysis. RESULTS: Of the 672 deaths, 566 patients
      (84.2%) received a transfusion of red blood cells. The PROM was 7.5% for the
      transfused patients versus 4.3% for those not transfused (p < 0.001). Transfused
      patients were older, more often female, had more emergency, on-pump, and redo
      procedures, and had a lower preoperative and on-bypass nadir hematocrit. Most
      other demographics were similar between the groups. Postoperatively, transfused
      patients were ventilated longer, had more renal and multisystem organ failure,
      and were more likely to die of infectious and pulmonary causes after longer
      intensive care unit and overall lengths of stay. CONCLUSIONS: Significant
      differences in PROM and the postoperative course leading to death between those
      with and without transfusion suggest the role of transfusion may be secondary to
      other patient-related factors. Recognizing that the relationship between
      transfusion and outcome after CABG remains incompletely understood, these
      findings are suggestive of a complex interaction of many variables.

PMID- 25757761
TI  - Improved wall motion of late gadolinium-enhanced myocardium after complete
      surgical revascularization.
AB  - BACKGROUND: Gadolinium-enhanced cardiac magnetic resonance (CMR) imaging suggests
      a low possibility of myocardial function improvement after revascularization if
      the transmural extent of late gadolinium enhancement (LGE) was over 50%. We
      evaluated myocardial wall motion in patients who underwent complete
      revascularization for left ventricular dysfunction. METHODS: Thirty-three
      patients with left ventricular dysfunction (ejection fraction <= 0.35) underwent
      complete revascularization. Gadolinium-enhanced CMR was performed preoperatively
      and postoperatively (postoperative 24.1 +/- 17.6 months). Postoperative coronary
      angiograms were also performed to confirm graft patency. Wall motion score and
      transmural extent of LGE were evaluated on a 16 segment model of short-axis
      images. RESULTS: Of 528 total segments, 373 dysfunctional segments (70.6%; 189
      hypokinesia, 177 akinesia, 6 dyskinesia, and 1 aneurysm) were evaluated for
      postoperative changes. When LGE was graded on a 5 point scale (absence of LGE,
      grade 0; LGE of 1% to 25%, grade 1; 26% to 50%, grade 2; 51% to 75%, grade 3; and
      76% to 100%, grade 4), LGE was found in 221 (59%) segments (grades 1, n = 80; 2,
      n = 55; 3, n = 37; and 4, n = 49). After revascularization, wall motion improved
      in 72.1% (269 of 373) of dysfunctional segments (128 of 189 hypokinesia versus
      141 of 184 akinesia; p = 0.055). Improved wall motion was observed in 77.0% (117
      of 152), 67.5% (54 of 80), 69.1% (38 of 55), 86.5% (32 of 37), and 57.1% (28 of
      49) of grades 0, 1, 2, 3, and 4 segments, respectively. CONCLUSIONS: Improved
      motion of late gadolinium-enhanced myocardium, even in segments showing
      transmural LGE of 75% or greater and akinesia, was observed after complete
      revascularization. An inverse proportional correlation between the transmural
      extent of LGE and wall motion improvement was not observed.

PMID- 25757762
TI  - Surgical strategy for retrograde type A aortic dissection based on long-term
      outcomes.
AB  - BACKGROUND: The optimal management of a retrograde type A aortic dissection
      (RAAD) is controversial, and few reports have discussed the long-term outcomes of
      surgical strategies. To determine the most appropriate strategy, we studied the
      early and late outcomes of RAAD cases. METHODS: From 1998 to 2014, 44 patients
      with RAAD (mean age of 63 +/- 11 years) underwent surgical repair. Ascending
      aortic replacement (AAR) was performed in 21 patients and ascending and total
      arch replacement (TAR) was performed in 23 patients. Eight of the patients who
      received TAR underwent complete resection of the primary tear in the distal arch
      or descending aorta (TAR-R[+]), whereas the remaining 15 patients received
      elephant trunk implantation as an alternative procedure for tear resection (TAR
      R[-]). The early and late outcomes (mean follow-up, 86.5 months) were evaluated.
      RESULTS: Hospital mortality occurred in 4 of the 44 (9.1%) patients, with no
      mortalities among the patients undergoing TAR-R[-]. There was a tendency toward a
      higher incidence of late aorta-related events in the AAR group, with a
      significantly higher patency rate of the false lumen in the proximal site of the
      residual aorta compared with the TAR group (p = 0.009). Furthermore, the 5-year
      rate of freedom from aortic growth greater than 50 mm was significantly lower
      after AAR than after TAR (p = 0.04). A multivariate analysis indicated that the
      initial ascending aortic diameter (odds ratio [OR], 1.5; p = 0.02) and AAR (OR,
      29.1; p = 0.01) were independent predictors of late aortic expansion.
      CONCLUSIONS: The surgical outcomes were acceptable in both the AAR and TAR
      groups. The long-term outcomes potentially support the aggressive adoption of TAR
      in relatively younger patients with significant ascending aortic enlargement at
      presentation.

PMID- 25757763
TI  - A population-based analysis of robotic-assisted mitral valve repair.
AB  - BACKGROUND: Robotic-assisted mitral valve repair is becoming more frequently
      performed in cardiac surgery. However, little is known about its utilization and
      safety at a national level. METHODS: Patients undergoing mitral valve repair in
      the United States from 2008 to 2012 were identified in the National Inpatient
      Sample. Inhospital mortality, complications, length of stay, and cost for
      patients undergoing robotic-assisted mitral valve repair were compared with
      patients undergoing nonrobotic procedures. RESULTS: We identified 50,408 isolated
      mitral valve repair surgeries, of which 3,145 were done with robotic assistance.
      In a propensity score matched analysis of 631 pairs of patients, we found no
      difference between patients undergoing robotic-assisted and nonrobotic-assisted
      mitral valve repair with respect to inhospital mortality, complications, or
      composite outcomes in unadjusted or multivariable analyses. Robotic-assisted
      mitral valve repair surgery was associated with a shorter median length of stay
      (4 versus 6 days, p < 0.001), and there was no difference in median total costs
      between the two procedures. CONCLUSIONS: In our analysis of a large national
      database with its inherent limitations, robotic-assisted mitral valve repair was
      found to be safe, with an acceptable morbidity and mortality profile.

PMID- 25757765
TI  - Epigenome profiling of specific plant cell types using a streamlined INTACT
      protocol and ChIP-seq.
AB  - Plants consist of many functionally specialized cell types, each with its own
      unique epigenome, transcriptome, and proteome. Characterization of these cell
      type-specific properties is essential to understanding cell fate specification
      and the responses of individual cell types to the environment. In this chapter we
      describe an approach to map chromatin features in specific cell types of
      Arabidopsis thaliana using nuclei purification from individual cell types with
      the INTACT method (isolation of nuclei tagged in specific cell types) followed by
      chromatin immunoprecipitation and high-throughput sequencing (ChIP-seq). The
      INTACT system employs two transgenes to generate affinity-labeled nuclei in the
      cell type of interest, and these tagged nuclei can then be selectively purified
      from tissue homogenates. The primary transgene encodes the nuclear tagging fusion
      protein (NTF), which consists of a nuclear envelope-targeting domain, the green
      fluorescent protein, and a biotin ligase recognition peptide, while the second
      transgene encodes the E. coli biotin ligase (BirA), which selectively
      biotinylates NTF. Expression of NTF and BirA in a specific cell type thus yields
      nuclei that are coated with biotin and can be purified by virtue of their
      affinity for streptavidin-coated magnetic beads. Compared with the original
      INTACT nuclei purification protocol, the procedure presented here is greatly
      simplified and shortened. After nuclei purification, we provide detailed
      instructions for chromatin isolation, shearing, and immunoprecipitation. Finally,
      we present a low input ChIP-seq library preparation protocol based on the nano
      ChIP-seq method of Adli and Bernstein, and we describe multiplex Illumina
      sequencing of these libraries to produce high quality, cell type-specific
      epigenome profiles at a relatively low cost. The procedures given here are
      optimized for Arabidopsis but should be easily adaptable to other plant species. 

PMID- 25757766
TI  - Whole-genome DNA methylation profiling with nucleotide resolution.
AB  - In many eukaryotic organisms, methylation at the fifth carbon of cytosine (5mC)
      is a stable epigenetic mark crucial for many biological processes, including cell
      differentiation, X-chromosome inactivation, transposon silencing, and genomic
      imprinting. DNA methylation can be stably inherited to the subsequent generation.
      It can also change dynamically in response to developmental cues or environmental
      stimuli, and is an important regulator for developmental switch and cell fate
      determination. Consequently, many human diseases are associated with aberrant DNA
      methylation. Gene-specific methylation analysis by sequencing of bisulfite
      treated genomic DNA has been instrumental in understanding how DNA methylation
      affects gene transcription. In recent years, techniques have been developed for
      genome-wide 5mC detection, and complete methylome at single base resolution has
      been reported for several organisms, providing unprecedented details on the
      dynamic nature of DNA methylation during development. With the advance in high
      throughput sequencing and the availability of genome sequences, mapping the
      methylome for species with complex genomes has become increasingly feasible. 

PMID- 25757764
TI  - PIK3R1 negatively regulates the epithelial-mesenchymal transition and stem-like
      phenotype of renal cancer cells through the AKT/GSK3beta/CTNNB1 signaling
      pathway.
AB  - The phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) pathway has been
      identified as an important pathway in renal cell carcinoma (RCC). We have
      reported a nonsense mutation in PIK3R1, which encodes the regulatory subunit of
      PI3K, in a metastatic RCC (mRCC), while the mutation was absent in the
      corresponding primary RCC (pRCC). To identify the function of PIK3R1 in RCC, we
      examined its expression in normal kidney, pRCC and mRCC by immunohistochemistry
      and real-time polymerase chain reaction. The expression of PIK3R1 significantly
      decreased in pRCC and was further reduced in mRCC compared with normal tissue.
      Besides, its expression levels were negatively correlated with T-category of
      tumor stage. Additionally, 786-O and A-704 cells with PIK3R1 depletion introduced
      by CRISPR/Cas9 system displayed enhanced proliferation, migration and epithelial
      mesenchymal transition (EMT), and acquired a stem-like phenotype. Moreover, the
      PIK3R1 depletion promoted the phosphorylation of AKT in the cells. The knockdown
      of AKT by shRNA reduced p-GSK3beta and CTNNB1 expression in the cells, while the
      depletion of CTNNB1 impaired stem-like phenotype of the cells. Overall, PIK3R1
      down-regulation in RCC promotes propagation, migration, EMT and stem-like
      phenotype in renal cancer cells through the AKT/GSK3beta/CTNNB1 pathway, and may
      contribute to progression and metastasis of RCC. 

PMID- 25757767
TI  - High-throughput nuclease-mediated probing of RNA secondary structure in plant
      transcriptomes.
AB  - Empirical measurement of RNA secondary structure is an invaluable tool that has
      provided a more complete understanding of the RNA life cycle and functionality of
      this extremely important molecule. In general, methods for probing structural
      information involve treating RNA with either a chemical or an enzyme that
      preferentially targets regions of the RNA in a single- or double-stranded
      conformation (ssRNA and dsRNA, respectively). Here, we describe an approach that
      utilizes a combination of ssRNA- and dsRNA-specific nuclease (ss- and dsRNase,
      respectively) treatments along with high-throughput sequencing technology to
      provide comprehensive and robust measurements of RNA secondary structure across
      entire plant transcriptomes. 

PMID- 25757768
TI  - Genome-wide mapping of DNase I hypersensitive sites in plants.
AB  - Genomic regions associated with regulatory proteins are known to be highly
      sensitive to DNase I digestion and are termed DNase I hypersensitive sites
      (DHSs). DHSs can be identified by DNase I digestion followed by high-throughput
      DNA sequencing (DNase-seq). DNase-seq has become a powerful technique for genome
      wide mapping of chromatin accessibility in eukaryotes with a sequenced genome. We
      have developed a DNase-seq procedure in plants. This procedure was adapted from
      the protocol originally developed for mammalian cell lines. It includes plant
      nuclei isolation, digestion of purified nuclei with DNase I, recovery of DNase
      trimmed DNA fragments, DNase-seq library development, Illumina sequencing and
      data analysis. We also introduce a barcoding system for library preparation. We
      have conducted DNase-seq in both Arabidopsis thaliana and rice, and developed
      genome-wide open chromatin maps in both species. These DHS datasets have been
      used to detect footprints from regulatory protein binding and to reveal genome
      wide nucleosome positioning patterns. 

PMID- 25757769
TI  - Characterization of in vivo DNA-binding events of plant transcription factors by
      ChIP-seq: experimental protocol and computational analysis.
AB  - Chromatin immunoprecipitation followed by next-generation sequencing (ChIP-seq)
      is a powerful technique for genome-wide identification of in vivo binding sites
      of DNA-binding proteins. The technique had been used to study many DNA-binding
      proteins in a broad variety of species. The basis of the ChIP-seq technique is
      the ability to covalently cross-link DNA and proteins that are located in very
      close proximity. This allows the use of an antibody against the (tagged) protein
      of interest to specifically enrich DNA-fragments bound by this protein. ChIP-seq
      can be performed using antibodies against the native protein or against tagged
      proteins. Using a specific antibody against a tag to immunoprecipitate tagged
      proteins eliminates the need for a specific antibody against the native protein
      and allows more experimental flexibility. In this chapter we present a complete
      workflow for experimental procedure and bioinformatic analysis that allows wet
      lab biologists to perform and analyze ChIP-seq experiments. 

PMID- 25757770
TI  - Identification of direct targets of plant transcription factors using the GR
      fusion technique.
AB  - The glucocorticoid receptor-dependent activation of plant transcription factors
      has proven to be a powerful tool for the identification of their direct target
      genes. In the absence of the synthetic steroid hormone dexamethasone (dex),
      transcription factors fused to the hormone-binding domain of the glucocorticoid
      receptor (TF-GR) are held in an inactive state, due to their cytoplasmic
      localization. This requires physical interaction with the heat shock protein 90
      (HSP90) complex. Hormone binding leads to disruption of the interaction between
      GR and HSP90 and allows TF-GR fusion proteins to enter the nucleus. Once inside
      the nucleus, they bind to specific DNA sequences and immediately activate or
      repress expression of their targets. This system is well suited for the
      identification of direct target genes of transcription factors in plants, as (A)
      there is little basal protein activity in the absence of dex, (B) steroid
      application leads to rapid transcription factor activation, (C) no side effects
      of dex treatment are observed on the physiology of the plant, and (D) secondary
      effects of transcription factor activity can be eliminated by simultaneous
      application of an inhibitor of protein biosynthesis, cycloheximide (cyc). In this
      chapter, we describe detailed protocols for the preparation of plant material,
      for dex and cyc treatment, for RNA extraction, and for the PCR-based or genome
      wide identification of direct targets of transcription factors fused to GR. 

PMID- 25757772
TI  - Tissue-specific gene expression profiling by cell sorting.
AB  - Many cell populations have been labeled using stable reporters containing a
      fluorescent protein. These same marker lines can be used to capture specific cell
      types or marked cell populations after a brief enzymatic digestion to dissociate
      tissues. Here, we describe the use of Fluorescence Activated Cell Sorting (FACS)
      to isolate a rare population of cells marked with Green Fluorescent Protein
      (GFP). The FACS is a powerful selection tool that can be used to isolate high
      quality RNA while selecting for fluorescence, cell size, and other properties. 

PMID- 25757771
TI  - Ribosome profiling: a tool for quantitative evaluation of dynamics in mRNA
      translation.
AB  - Translational regulation is important for plant growth, metabolism, and
      acclimation to environmental challenges. Ribosome profiling involves the nuclease
      digestion of mRNAs associated with ribosomes and mapping of the generated
      ribosome-protected footprints to transcripts. This is useful for investigation of
      translational regulation. Here we present a detailed method to generate, purify,
      and high-throughput-sequence ribosome footprints from Arabidopsis thaliana using
      two different isolation methods, namely, conventional differential centrifugation
      and the translating ribosome affinity purification (TRAP) technology. These
      methodologies provide researchers with an opportunity to quantitatively assess
      with high-resolution the translational activity of individual mRNAs by
      determination of the position and number of ribosomes in the corresponding mRNA.
      The results can provide insights into the translation of upstream open reading
      frames, alternatively spliced transcripts, short open reading frames, and other
      aspects of translation. 

PMID- 25757773
TI  - Translating Ribosome Affinity Purification (TRAP) followed by RNA sequencing
      technology (TRAP-SEQ) for quantitative assessment of plant translatomes.
AB  - Translating Ribosome Affinity Purification (TRAP) is a technology to isolate the
      population of mRNAs associated with at least one 80S ribosome, referred as the
      translatome. TRAP is based on the expression of an epitope-tagged version of a
      ribosomal protein and the affinity purification of ribosomes and associated mRNAs
      using antibodies conjugated to agarose beads. Quantitative assessment of the
      translatome is achieved by direct RNA sequencing (RNA-SEQ), which provides
      accurate quantitation of ribosome-associated mRNAs and reveals alternatively
      spliced isoforms. Here we present a detailed procedure for TRAP, as well as a
      guide for preparation of RNA-SEQ libraries (TRAP-SEQ) and a primary data
      analysis. This methodology enables the study of translational dynamic by
      assessing rapid changes in translatomes, at organ or cell-type level, during
      development or in response to endogenous or exogenous stimuli. 

PMID- 25757774
TI  - Rapid immunopurification of ribonucleoprotein complexes of plants.
AB  - Hundreds of RNA binding proteins posttranscriptionally regulate gene expression,
      but relatively few have been characterized in plants. One successful approach to
      determine protein function has been to identify interacting molecules and the
      conditions of their association. The ribonucleoprotein immunopurification (RIP)
      assay facilitates the identification and quantitative comparison of RNA
      association to specific proteins under different experimental conditions. A
      variety of molecular techniques can be used to analyze the enriched RNAs, whether
      few as in the case of highly specific interactions, or many. Identification of
      associated RNAs can inform hypothesis generation about the processes or pathways
      regulated by the target protein. Downstream analysis of associated RNA sequences
      can lead to the identification of candidate motifs or features that mediate the
      protein-RNA interaction. We present a rapid method for RIP from tissues of plants
      that is suitable for experiments that require immediate tissue cryopreservation,
      such as monitoring a rapid response to an environmental stimulus. 

PMID- 25757775
TI  - Metabolomic profiling of plant tissues.
AB  - Metabolomics is a powerful discipline aimed at a comprehensive and global
      analysis of the metabolites present in a cell, tissue, or organism, and to which
      increasing attention has been paid in the last few years. Given the high
      diversity in physical and chemical properties of plant metabolites, not a single
      method is able to analyze them all.Here we describe two techniques for the
      profiling of two quite different groups of metabolites: polar and semi-polar
      secondary metabolites, including many of those involved in plant response to
      biotic and abiotic stress, and volatile compounds, which include those
      responsible of most of our perception of food flavor. According to these
      techniques, polar and semi-polar metabolites are extracted in methanol, separated
      by liquid chromatography (UPLC), and detected by a UV-VIS detector (PDA) and a
      time-of-flight (ToF) mass spectrometer. Volatile compounds, on the other hand,
      are extracted by headspace solid phase microextraction (HS-SPME), and separated
      and detected by gas chromatography coupled to mass spectrometry (GC-MS). 

PMID- 25757776
TI  - Targeted plant genome editing via the CRISPR/Cas9 technology.
AB  - Targeted modification of plant genome is key for elucidating and manipulating
      gene functions in basic and applied plant research. The CRISPR (clustered
      regularly interspaced short palindromic repeats)/CRISPR-associated protein (Cas)
      technology is emerging as a powerful genome editing tool in diverse organisms.
      This technology utilizes an easily reprogrammable guide RNA (gRNA) to guide
      Streptococcus pyogenes Cas9 endonuclease to generate a DNA double-strand break
      (DSB) within an intended genomic sequence and subsequently stimulate chromosomal
      mutagenesis or homologous recombination near the DSB site through cellular DNA
      repair machineries. In this chapter, we describe the detailed procedure to
      design, construct, and evaluate dual gRNAs for plant codon-optimized Cas9
      (pcoCas9)-mediated genome editing using Arabidopsis thaliana and Nicotiana
      benthamiana protoplasts as model cellular systems. We also discuss strategies to
      apply the CRISPR/Cas9 system to generating targeted genome modifications in whole
      plants. 

PMID- 25757777
TI  - QTL mapping using high-throughput sequencing.
AB  - Quantitative trait locus (QTL) mapping in plants dates to the 1980s (Stuber et
      al. Crop Sci 27: 639-648, 1987; Paterson et al. Nature 335: 721-726, 1988), but
      earlier studies were often hindered by the expense and time required to identify
      large numbers of polymorphic genetic markers that differentiated the parental
      genotypes and then to genotype them on large segregating mapping populations.
      High-throughput sequencing has provided an efficient means to discover single
      nucleotide polymorphisms (SNPs) that can then be assayed rapidly on large
      populations with array-based techniques (Gupta et al. Heredity 101: 5-18, 2008).
      Alternatively, high-throughput sequencing methods such as restriction site
      associated DNA sequencing (RAD-Seq) (Davey et al. Nat Rev Genet 12: 499-510,
      2011; Baird et al. PloS ONE 3: e3376, 2008) and genotyping-by-sequencing (GBS)
      (Elshire et al. PLoS One 6: 2011; Glaubitz et al. PLoS One 9: e90346, 2014) can
      be used to identify and genotype polymorphic markers directly. Linkage
      disequilibrium (LD) between markers and causal variants is needed to detect QTL.
      The earliest QTL mapping methods used backcross and F2 generations of crosses
      between inbred lines, which have high levels of linkage disequilibrium (dependent
      entirely on the recombination frequency between chromosomal positions), to ensure
      that QTL would have sufficiently high linkage disequilibrium with one or more
      markers on sparse genetic linkage maps. The downside of this approach is that
      resolution of QTL positions is poor. The sequencing technology revolution, by
      facilitating genotyping of vastly more markers than was previously feasible, has
      allowed researchers to map QTL in situations of lower linkage disequilibrium, and
      consequently, at higher resolution. We provide a review of methods to identify
      QTL with higher precision than was previously possible. We discuss modifications
      of the traditional biparental mapping population that provide higher resolution
      of QTL positions, QTL fine-mapping procedures, and genome-wide association
      studies, all of which are greatly facilitated by high-throughput sequencing
      methods. Each of these procedures has many variants, and consequently many
      details to consider; we focus our chapter on the consequences of practical
      decisions that researchers make when designing QTL mapping studies and when
      analyzing the resulting data. The ultimate goal of many of these studies is to
      resolve a QTL to its causal sequence variation.

PMID- 25757778
TI  - Quantitating plant microRNA-mediated target repression using a dual-luciferase
      transient expression system.
AB  - microRNA (miRNA) mediated repression of target genes plays essential roles in a
      variety of functions in plants. An easy-to-use method that can effectively
      validate functional miRNA-target interactions in plants thus is of particular
      interest. Here, we describe an Agrobacterium tumefaciens-mediated in vivo assay
      utilizing a dual-luciferase reporter system. With this method, the strength of
      miRNA-mediated target repression can be quantified at both the mRNA (via qRT-PCR)
      and protein (via dual-luciferase assay) levels quickly and accurately. 

PMID- 25757779
TI  - Persistent virus-induced gene silencing in asymptomatic accessions of
      Arabidopsis.
AB  - Coupled with the advantages afforded by the model plant Arabidopsis, virus
      induced gene silencing (VIGS) offers a rapid means to assess gene function. The
      geminivirus vector based on Cabbage leaf curl virus described here has the
      benefits of small insert size and persistent silencing of the target gene through
      the life cycle of the plant. Here, we show that genetic variation in the vast
      collection of Arabidopsis accessions can be leveraged to ameliorate viral
      symptomology that accompanies the VIGS procedure. The plasticity of phenotypes
      under different day lengths or temperature conditions can be exploited to achieve
      maximum silencing efficacy in either vegetative or inflorescence tissue,
      according to the question being asked. Protocols and vectors for Agro
      infiltration of primary leaves, subapical pricking in older plants, and
      microprojectile bombardment are described. 

PMID- 25757780
TI  - A user's guide to the Arabidopsis T-DNA insertion mutant collections.
AB  - The T-DNA sequence-indexed mutant collections contain insertional mutants for
      most Arabidopsis thaliana genes and have played an important role in plant
      biology research for almost two decades. By providing a large source of mutant
      alleles for in vivo characterization of gene function, this resource has been
      leveraged thousands of times to study a wide range of problems in plant biology.
      Our primary goal in this chapter is to provide a general guide to strategies for
      the effective use of the data and materials in these collections. To do this, we
      provide a general introduction to the T-DNA insertional sequence-indexed mutant
      collections with a focus on how best to use the available data sources for good
      line selection. As isolation of a homozygous line is a common next step once a
      potential disruption line has been identified, the second half of the chapter
      provides a step-by-step guide for the design and implementation of a T-DNA
      genotyping pipeline. Finally, we describe interpretation of genotyping results
      and include a troubleshooting section for common types of segregation distortions
      that we have observed. In this chapter we introduce both basic concepts and
      specific applications to both new and more experienced users of the collections
      for the design and implementation of small- to large-scale genotyping pipelines. 

PMID- 25757781
TI  - Genome-wide association mapping in plants exemplified for root growth in
      Arabidopsis thaliana.
AB  - Genome-wide association (GWA) mapping is a powerful technique to address the
      molecular basis of genotype to phenotype relationships and to map regulators of
      biological processes. This chapter presents a protocol for genome-wide
      association mapping in Arabidopsis thaliana using the user-friendly internet
      application GWAPP, and provides a specific protocol for acquiring root trait data
      suitable for GWA studies using the semi-automated, high-throughput phenotyping
      pipeline BRAT for early root growth. 

PMID- 25757782
TI  - Tilling by sequencing.
AB  - TILLING is a method to find mutations in a gene of interest by scanning amplicons
      from a mutagenized population for sequence changes, commonly a single nucleotide.
      In the past 5 years, mutation detection by sequencing has become increasingly
      popular. This chapter details the experimental flow for TILLING-by-Sequencing,
      highlighting the critical steps involved in tridimensional pooling of genomic DNA
      templates, preparation of libraries for high-throughput sequencing, and
      bioinformatic processing of the sequence data. 

PMID- 25757783
TI  - SHOREmap v3.0: fast and accurate identification of causal mutations from forward
      genetic screens.
AB  - Whole-genome resequencing of pools of recombinant mutant genomes allows direct
      linking of phenotypic traits to causal mutations. Such analysis, called mapping
      by-sequencing, combines classical genetic mapping and next-generation sequencing
      by relying on selection-induced patterns within genome-wide allele frequency (AF)
      in pooled genomes. Mapping-by-sequencing can be performed with computational
      tools such as SHOREmap. Previous versions of SHOREmap, however, did not implement
      standardized analyses, but were specifically designed for particular experimental
      settings. Here, we introduce the usage of a novel and advanced implementation of
      SHOREmap (version 3.0), including several new features like file readers for
      commonly used file formats, SNP marker selection, and a stable calculation of
      mapping intervals. SHOREmap can be downloaded at shoremap.org. 

PMID- 25757784
TI  - Software-assisted stacking of gene modules using GoldenBraid 2.0 DNA-assembly
      framework.
AB  - GoldenBraid (GB) is a modular DNA assembly technology for plant multigene
      engineering based on type IIS restriction enzymes. GB speeds up the assembly of
      transcriptional units from standard genetic parts and facilitates the stacking of
      several genes within the same T-DNA in few days. GBcloning is software-assisted
      with a set of online tools. The GBDomesticator tool assists in the adaptation of
      DNA parts to the GBstandard. The combination of GB-adapted parts to build new
      transcriptional units is assisted by the GB TU Assembler tool. Finally, the
      assembly of multigene modules is simulated by the GB Binary Assembler. All the
      software tools are available at www.gbcloning.org . Here, we describe in detail
      the assembly methodology to create a multigene construct with three
      transcriptional units for polyphenol metabolic engineering in plants. 

PMID- 25757785
TI  - Ligation-independent cloning for plant research.
AB  - Molecular cloning is a vital step in much of today's plant biological research.
      Particularly, when a species is amenable to transgenic manipulation, cloning
      enables detailed study of gene and protein function in vivo. Therefore, accurate,
      consistent, and efficient cloning methods have the potential to accelerate
      biological research. Traditional restriction-enzyme/ligase-based strategies are
      often inefficient, while novel alternative methods can be less economical. We
      have recently optimized a method for Ligation-Independent Cloning (LIC) that is
      both efficient and economical. We have developed a large set of LIC-compatible
      plasmids for application in plant research. These include dedicated vectors for
      gene expression analysis, protein localization studies, and protein
      misexpression. We describe a detailed protocol that allows the reliable
      generation of plant transformation-ready constructs from PCR fragments in 2-3
      days. 

PMID- 25757786
TI  - Gene functional analysis using protoplast transient assays.
AB  - The protoplast transient assay system has been widely used for rapid functional
      analyses of genes using cellular and biochemical approaches. This system has been
      increasingly employed for functional genetic studies using double-stranded (ds)
      RNA interference (RNAi). Here, we describe a modified procedure for the isolation
      of protoplasts from leaf mesophyll cells of 14-day-old Arabidopsis thaliana. This
      modification significantly simplifies and speeds up functional studies without
      compromising the yield and the viability of protoplasts. We also present the
      procedure for the isolation and transfection of protoplasts from mesophyll cells
      of an emerging model grass species, Brachypodium distachyon. Further, we detail
      procedures for RNAi-based functional studies of genes using transient expression
      of in vitro synthesized dsRNA in protoplasts. 

PMID- 25757787
TI  - Descriptive vs. mechanistic network models in plant development in the post
      genomic era.
AB  - Network modeling is now a widespread practice in systems biology, as well as in
      integrative genomics, and it constitutes a rich and diverse scientific research
      field. A conceptually clear understanding of the reasoning behind the main
      existing modeling approaches, and their associated technical terminologies, is
      required to avoid confusions and accelerate the transition towards an undeniable
      necessary more quantitative, multidisciplinary approach to biology. Herein, we
      focus on two main network-based modeling approaches that are commonly used
      depending on the information available and the intended goals: inference-based
      methods and system dynamics approaches. As far as data-based network inference
      methods are concerned, they enable the discovery of potential functional
      influences among molecular components. On the other hand, experimentally grounded
      network dynamical models have been shown to be perfectly suited for the
      mechanistic study of developmental processes. How do these two perspectives
      relate to each other? In this chapter, we describe and compare both approaches
      and then apply them to a given specific developmental module. Along with the step
      by-step practical implementation of each approach, we also focus on discussing
      their respective goals, utility, assumptions, and associated limitations. We use
      the gene regulatory network (GRN) involved in Arabidopsis thaliana Root Stem Cell
      Niche patterning as our illustrative example. We show that descriptive models
      based on functional genomics data can provide important background information
      consistent with experimentally supported functional relationships integrated in
      mechanistic GRN models. The rationale of analysis and modeling can be applied to
      any other well-characterized functional developmental module in multicellular
      organisms, like plants and animals. 

PMID- 25757788
TI  - Analysis and visualization of RNA-Seq expression data using RStudio,
      Bioconductor, and Integrated Genome Browser.
AB  - Sequencing costs are falling, but the cost of data analysis remains high, often
      because unforeseen problems arise, such as insufficient depth of sequencing or
      batch effects. Experimenting with data analysis methods during the planning phase
      of an experiment can reveal unanticipated problems and build valuable
      bioinformatics expertise in the organism or process being studied. This protocol
      describes using R Markdown and RStudio, user-friendly tools for statistical
      analysis and reproducible research in bioinformatics, to analyze and document the
      analysis of an example RNA-Seq data set from tomato pollen undergoing chronic
      heat stress. Also, we show how to use Integrated Genome Browser to visualize read
      coverage graphs for differentially expressed genes. Applying the protocol
      described here and using the provided data sets represent a useful first step
      toward building RNA-Seq data analysis expertise in a research group. 

PMID- 25757789
TI  - Constructing simple biological networks for understanding complex high-throughput
      data in plants.
AB  - Technological advances in the last decade have enabled biologists to produce
      increasing amounts of information for the transcriptome, proteome, interactome,
      and other -omics data sets in many model organisms. A major challenge is
      integration and biological interpretation of these massive data sets in order to
      generate testable hypotheses about gene regulatory networks or molecular
      mechanisms that govern system behaviors. Constructing gene networks requires
      bioinformatics skills to adequately manage, integrate, analyze and productively
      use the data to generate biological insights. In this chapter, we provide
      detailed methods for users without prior knowledge of bioinformatics to construct
      gene networks and derive hypotheses that can be experimentally verified. Step-by
      step instructions for acquiring, integrating, analyzing, and visualizing genome
      wide data are provided for two widely used open source platforms, R and Cytoscape
      platforms. The examples provided are based on Arabidopsis data, but the protocols
      presented should be readily applicable to any organism for which similar data can
      be obtained. 

PMID- 25757790
TI  - Resilience predicts functional outcomes in people aging with disability: a
      longitudinal investigation.
AB  - OBJECTIVES: To investigate the links between resilience and depressive symptoms,
      social functioning, and physical functioning in people aging with disability and
      to investigate the effects of resilience on change in functional outcomes over
      time. DESIGN: Longitudinal postal survey. SETTING: Surveys were mailed to a
      community sample of individuals with 1 of 4 diagnoses: multiple sclerosis,
      muscular dystrophy, postpoliomyelitis syndrome, or spinal cord injury. The survey
      response rate was 91% at baseline and 86% at follow-up. PARTICIPANTS: A
      convenience sample of community-dwelling individuals (N=1594; age range, 20-94y)
      with multiple sclerosis, muscular dystrophy, postpoliomyelitis syndrome, or
      spinal cord injury. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Patient
      Health Questionnaire-9 (to assess depressive symptoms) and Patient Reported
      Outcomes Measurement Information System (to assess social role satisfaction and
      physical functioning). RESULTS: At baseline, resilience was negatively correlated
      with depressive symptoms (r=-.55) and positively correlated with social and
      physical functioning (r=.49 and r=.17, respectively). Controlling for baseline
      outcomes, greater baseline resilience predicted a decrease in depressive symptoms
      (partial r=-.12) and an increase in social functioning (partial r=.12) 3 years
      later. CONCLUSIONS: The findings are consistent with a view of resilience as a
      protective factor that supports optimal functioning in people aging with
      disability.

PMID- 25757791
TI  - People with disabilities in the United States.
AB  - A recent compilation of published disability statistics available for the United
      States showcases the pervasive and persistent disparities that exist between
      people with and without disabilities across multiple fronts, including
      employment, earnings, poverty, and participation in safety net programs.
      Understanding the relevance of these statistics within the current policy
      environment can help guide further innovations to improve the lives of persons
      with disabilities in the United States. 

PMID- 25757792
TI  - Brief overview and assessment of the role and benefits of cognitive
      rehabilitation.
AB  - Cognition is one of our most important attributes. Arresting its decline, whether
      in association with normal aging or a diagnosis of mild cognitive impairment,
      acquired brain injury, or dementia, concerns everyone, regardless of whether
      their role is that of spouse, child, or clinician. This article provides a brief,
      and by necessity, somewhat superficial appraisal of the status of our knowledge
      of the benefits of cognitive rehabilitation in these conditions and the authors'
      assessment of its strengths and weaknesses. In summary, there is support for the
      belief that participation in exercise as well as socially and cognitively
      stimulating activities (whether or not rehabilitative in nature) is beneficial
      for all but perhaps those with the most severe dementia. Focused efforts at
      cognitive training/rehabilitation also appear potentially helpful but are best
      established for those with acquired brain injury. There are, however, caveats to
      this assessment. For example, cognitive retraining is resource and time intensive
      while, even for those most likely to benefit, its impact on their daily
      activities and quality of life remains unclear. In addition, responses to
      training may vary from person to person and are likely to be influenced by
      factors such as an individual's acceptance of the need for assistance. Future
      research may benefit from continued efforts to treat the patient holistically,
      fit the treatment to those most likely to benefit, and encouraging the
      translation of training effects to functioning in the real world. 

PMID- 25757793
TI  - One-pot synthesis of doxorubicin-loaded multiresponsive nanogels based on
      hyperbranched polyglycerol.
AB  - Doxorubicin-loaded nanogels with multiresponsive properties are prepared using
      hyperbranched polyglycerol as a biocompatible scaffold. The nanogels are
      synthesized in a single step combining free-radical polymerization and a mild
      nanoprecipitation technique. The nanogels respond to different biological stimuli
      such as low pH and reductive environments, resulting in a more efficient cell
      proliferation inhibition in A549 cells. 

PMID- 25757794
TI  - Wolves adapt territory size, not pack size to local habitat quality.
AB  - 1. Although local variation in territorial predator density is often correlated
      with habitat quality, the causal mechanism underlying this frequently observed
      association is poorly understood and could stem from facultative adjustment in
      either group size or territory size. 2. To test between these alternative
      hypotheses, we used a novel statistical framework to construct a winter
      population-level utilization distribution for wolves (Canis lupus) in northern
      Ontario, which we then linked to a suite of environmental variables to determine
      factors influencing wolf space use. Next, we compared habitat quality metrics
      emerging from this analysis as well as an independent measure of prey abundance,
      with pack size and territory size to investigate which hypothesis was most
      supported by the data. 3. We show that wolf space use patterns were concentrated
      near deciduous, mixed deciduous/coniferous and disturbed forest stands favoured
      by moose (Alces alces), the predominant prey species in the diet of wolves in
      northern Ontario, and in proximity to linear corridors, including shorelines and
      road networks remaining from commercial forestry activities. 4. We then
      demonstrate that landscape metrics of wolf habitat quality - projected wolf use,
      probability of moose occupancy and proportion of preferred land cover classes -
      were inversely related to territory size but unrelated to pack size. 5. These
      results suggest that wolves in boreal ecosystems alter territory size, but not
      pack size, in response to local variation in habitat quality. This could be an
      adaptive strategy to balance trade-offs between territorial defence costs and
      energetic gains due to resource acquisition. That pack size was not responsive to
      habitat quality suggests that variation in group size is influenced by other
      factors such as intraspecific competition between wolf packs.

PMID- 25757797
TI  - Differential relations between juvenile psychopathic traits and resting state
      network connectivity.
AB  - Traditionally, neurobiological research on psychopathy has focused on categorical
      differences in adults. However, there is evidence that psychopathy is best
      described by a set of relatively independent personality dimensions, that is,
      callous-unemotional, grandiose-manipulative, and impulsive-irresponsible traits,
      which can be reliably detected in juveniles, allowing investigation of the neural
      mechanisms leading to psychopathy. Furthermore, complex psychiatric disorders
      like psychopathy are increasingly being conceptualized as disorders of brain
      networks. The intrinsic organization of the brain in such networks is reflected
      by coherent fluctuations in resting state networks (RSNs), but these have not
      been studied in sufficient detail in relation to juvenile psychopathic traits
      yet. The current study investigated the distinct associations of juvenile
      psychopathic traits dimensions with RSN connectivity. Resting-state functional
      MRI and independent component analysis were used to assess RSN connectivity in a
      large sample of adolescents (n = 130, mean age 17.8 years) from a childhood
      arrestee cohort. Associations between scores on each of the three psychopathic
      traits dimensions and connectivity within and between relevant RSNs were
      investigated. Callous-unemotional traits were related to aberrant connectivity
      patterns of the default mode network, which has been implicated in self
      referential and moral processes. Impulsive-irresponsible traits were associated
      with altered connectivity patterns in the frontoparietal cognitive control
      networks. Grandiose-manipulative traits were not associated with altered
      connectivity patterns. These findings confirm the association between
      psychopathic traits and brain network connectivity, and considerably add to
      emerging evidence supporting neurobiological heterogeneity in the processes
      leading to psychopathy.

PMID- 25757795
TI  - Asexual expansion of Toxoplasma gondii merozoites is distinct from tachyzoites
      and entails expression of non-overlapping gene families to attach, invade, and
      replicate within feline enterocytes.
AB  - BACKGROUND: The apicomplexan parasite Toxoplasma gondii is cosmopolitan in
      nature, largely as a result of its highly flexible life cycle. Felids are its
      only definitive hosts and a wide range of mammals and birds serve as intermediate
      hosts. The latent bradyzoite stage is orally infectious in all warm-blooded
      vertebrates and establishes chronic, transmissible infections. When bradyzoites
      are ingested by felids, they transform into merozoites in enterocytes and expand
      asexually as part of their coccidian life cycle. In all other intermediate hosts,
      however, bradyzoites differentiate exclusively to tachyzoites, and disseminate
      extraintestinally to many cell types. Both merozoites and tachyzoites undergo
      rapid asexual population expansion, yet possess different effector fates with
      respect to the cells and tissues they develop in and the subsequent stages they
      differentiate into. RESULTS: To determine whether merozoites utilize distinct
      suites of genes to attach, invade, and replicate within feline enterocytes, we
      performed comparative transcriptional profiling on purified tachyzoites and
      merozoites. We used high-throughput RNA-Seq to compare the merozoite and
      tachyzoite transcriptomes. 8323 genes were annotated with sequence reads across
      the two asexually replicating stages of the parasite life cycle. Metabolism was
      similar between the two replicating stages. However, significant stage-specific
      expression differences were measured, with 312 transcripts exclusive to
      merozoites versus 453 exclusive to tachyzoites. Genes coding for 177 predicted
      secreted proteins and 64 membrane- associated proteins were annotated as
      merozoite-specific. The vast majority of known dense-granule (GRA), microneme
      (MIC), and rhoptry (ROP) genes were not expressed in merozoites. In contrast, a
      large set of surface proteins (SRS) was expressed exclusively in merozoites.
      CONCLUSIONS: The distinct expression profiles of merozoites and tachyzoites
      reveal significant additional complexity within the T. gondii life cycle,
      demonstrating that merozoites are distinct asexual dividing stages which are
      uniquely adapted to their niche and biological purpose.

PMID- 25757798
TI  - Platelet mitochondrial activity and pesticide exposure in early Parkinson's
      disease.
AB  - BACKGROUND: Mitochondrial dysfunction has been implicated in the pathogenesis of
      Parkinson's disease (PD), but the cause of this dysfunction is unclear. METHODS:
      Platelet mitochondrial complex I and I/III (nicotinamide adenine dinucleotide
      cytochrome c reductase, NCCR) activities were measured in early PD patients and
      matched controls enrolled in a population-based case-control study. Ambient
      agricultural pesticide exposures were assessed with a geographic information
      system and California Pesticide Use Registry. RESULTS: In contrast to some
      previous reports, we found no differences in complex I and I/III activities in
      subjects with PD and controls. We did find that NCCR activity correlated with
      subjects' exposure to pesticides known to inhibit mitochondrial activity
      regardless of their diagnosis. CONCLUSIONS: Electron transport chain (ETC)
      activity is not altered in PD in this well-characterized cohort when compared
      with community-matched controls but appears to be affected by environmental
      toxins, such as mitochondria-inhibiting pesticides.

PMID- 25757799
TI  - A polyphasic approach leading to the revision of the genus Planktothrix
      (Cyanobacteria) and its type species, P. agardhii, and proposal for integrating
      the emended valid botanical taxa, as well as three new species, Planktothrix
      paucivesiculata sp. nov.ICNP, Planktothrix tepida sp. nov.ICNP, and Planktothrix
      serta sp. nov.ICNP, as genus and species names with nomenclatural standing under
      the ICNP.
AB  - Twenty strains of Planktothrix and five of 'Oscillatoria' were characterized by a
      polyphasic approach, for clarification of their taxonomic relationships. Emphasis
      was given to the strains (17) of the Pasteur Culture Collection of Cyanobacteria
      (PCC). Phenotypic characters analyzed comprised morphology, phycobiliprotein
      composition, temperature and salinity tolerance. The gvpA gas vesicle gene was
      detected by PCR in all strains, and transmission electron microscopy confirmed
      gas vesicle formation in the strains of 'Oscillatoria'. MALDI-TOF mass
      spectrometry revealed 13 chemotypes, nine of which produce microcystins. A multi
      locus sequence typing (MLST) analysis was conducted using individual and
      concatenated nucleotide sequences of the 16S rDNA, internal transcribed spacer
      (ITS), gyrB, rpoC1 and rpoB. The results highlighted an unexpected diversity
      within the genus Planktothrix, showing that the five strains of 'Oscillatoria'
      need to be included in this taxon. Consequently, the genus consists of seven
      phylogenetic clusters, three of which represent new species, named Planktothrix
      paucivesiculata sp. nov.ICNP (type strain: PCC 8926T), Planktothrix tepida sp.
      nov.ICNP (type strain: PCC 9214T) and Planktothrix serta sp. nov.ICNP (type
      strain: PCC 8927T). These, together with the emended genus Planktothrix and its
      type species P. agardhii, valid taxa under the ICN, are described/re-described
      for gaining nomenclatural standing under the ICNP.

PMID- 25757800
TI  - Complete magnesiothermic reduction reaction of vertically aligned mesoporous
      silica channels to form pure silicon nanoparticles.
AB  - Owing to its simplicity and low temperature conditions, magnesiothermic reduction
      of silica is one of the most powerful methods for producing silicon
      nanostructures. However, incomplete reduction takes place in this process leaving
      unconverted silica under the silicon layer. This phenomenon limits the use of
      this method for the rational design of silicon structures. In this effort, a
      technique that enables complete magnesiothermic reduction of silica to form
      silicon has been developed. The procedure involves magnesium promoted reduction
      of vertically oriented mesoporous silica channels on reduced graphene oxides
      (rGO) sheets. The mesopores play a significant role in effectively enabling
      magnesium gas to interact with silica through a large number of reaction sites.
      Utilizing this approach, highly uniform, ca. 10 nm sized silicon nanoparticles
      are generated without contamination by unreacted silica. The new method for
      complete magnesiothermic reduction of mesoporous silica approach provides a
      foundation for the rational design of silicon structures.

PMID- 25757801
TI  - Mechanistic understanding of human-wildlife conflict through a novel application
      of dynamic occupancy models.
AB  - Crop and livestock depredation by wildlife is a primary driver of human-wildlife
      conflict, a problem that threatens the coexistence of people and wildlife
      globally. Understanding mechanisms that underlie depredation patterns holds the
      key to mitigating conflicts across time and space. However, most studies do not
      consider imperfect detection and reporting of conflicts, which may lead to
      incorrect inference regarding its spatiotemporal drivers. We applied dynamic
      occupancy models to elephant crop depredation data from India between 2005 and
      2011 to estimate crop depredation occurrence and model its underlying dynamics as
      a function of spatiotemporal covariates while accounting for imperfect detection
      of conflicts. The probability of detecting conflicts was consistently <1.0 and
      was negatively influenced by distance to roads and elevation gradient, averaging
      0.08-0.56 across primary periods (distinct agricultural seasons within each
      year). The probability of crop depredation occurrence ranged from 0.29 (SE 0.09)
      to 0.96 (SE 0.04). The probability that sites raided by elephants in primary
      period t would not be raided in primary period t + 1 varied with elevation
      gradient in different seasons and was influenced negatively by mean rainfall and
      village density and positively by distance to forests. Negative effects of
      rainfall variation and distance to forests best explained variation in the
      probability that sites not raided by elephants in primary period t would be
      raided in primary period t + 1. With our novel application of occupancy models,
      we teased apart the spatiotemporal drivers of conflicts from factors that
      influence how they are observed, thereby allowing more reliable inference on
      mechanisms underlying observed conflict patterns. We found that factors
      associated with increased crop accessibility and availability (e.g., distance to
      forests and rainfall patterns) were key drivers of elephant crop depredation
      dynamics. Such an understanding is essential for rigorous prediction of future
      conflicts, a critical requirement for effective conflict management in the
      context of increasing human-wildlife interactions. 

PMID- 25757803
TI  - Multiple system atrophy: using clinical pharmacology to reveal pathophysiology.
AB  - Despite similarities in their clinical presentation, patients with multiple
      system atrophy (MSA) have residual sympathetic tone and intact post-ganglionic
      noradrenergic fibers, whereas patients with pure autonomic failure (PAF) and
      Parkinson disease have efferent post-ganglionic autonomic denervation. These
      differences are apparent biochemically, as well as in neurophysiological testing,
      with near normal plasma norephrine in MSA but very low levels in PAF. These
      differences are also reflected in the response patients have to drugs that
      interact with the autonomic nervous system. For example, the ganglionic blocker
      trimethaphan reduces residual sympathetic tone and lowers blood pressure in MSA,
      but less so in PAF. Conversely, the alpha2-antagonist yohimbine produces a
      greater increase in blood pressure in MSA compared to PAF, although significant
      overlap exists. In normal subjects, the norepinephrine reuptake (NET) inhibitor
      atomoxetine has little effect on blood pressure because the peripheral effects of
      NET inhibition that result in noradrenergic vasoconstriction are counteracted by
      the increase in brain norepinephrine, which reduces sympathetic outflow (a
      clonidine-like effect). In patients with autonomic failure and intact peripheral
      noradrenergic fibers, only the peripheral vasoconstriction is apparent. This
      translates to a significant pressor effect of atomoxetine in MSA, but not in PAF
      patients. Thus, pharmacological probes can be used to understand the
      pathophysiology of the different forms of autonomic failure, assist in the
      diagnosis, and aid in the management of orthostatic hypotension. 

PMID- 25757802
TI  - Impact of neighborhood socioeconomic conditions on the risk of stroke in Japan.
AB  - BACKGROUND: Neighborhood deprivation has been shown in many studies to be an
      influential factor in cardiovascular disease risk. However, no previous studies
      have examined the effect of neighborhood socioeconomic conditions on the risk of
      stroke in Asian countries. METHODS: This study investigated whether neighborhood
      deprivation was associated with the risk of stroke and stroke death using data
      from the Japan Public Health Center-based Prospective Study. We calculated the
      adjusted hazard ratios of stroke mortality (mean follow-up, 16.4 years) and
      stroke incidence (mean follow-up, 15.4 years) according to the area deprivation
      index (ADI) among 90 843 Japanese men and women aged 40-69 years. A Cox
      proportional-hazard regression model using a shared frailty model was applied.
      RESULTS: The adjusted hazard ratios of stroke incidence, in order of increasing
      deprivation with reference to the least deprived area, were 1.16 (95% CI, 1.04
      1.29), 1.12 (95% CI, 1.00-1.26), 1.18 (95% CI, 1.02-1.35), and 1.19 (95% CI, 1.01
      1.41), after adjustment for individual socioeconomic conditions. Behavioral and
      psychosocial factors attenuated the association, but the association remained
      significant. The associations were explained by adjusting for biological
      cardiovascular risk factors. No significant association with stroke mortality was
      identified. CONCLUSIONS: Our results indicate that the neighborhood deprivation
      level influences stroke incidence in Japan, suggesting that area socioeconomic
      conditions could be a potential target for public health intervention to reduce
      the risk of stroke.

PMID- 25757806
TI  - Prediction of chronic lymphocytic leukaemia incidence in Germany and of patients
      ineligible for standard chemotherapy.
AB  - Chronic lymphocytic leukaemia (CLL) patients often remain asymptomatic for
      several years after diagnosis. When the disease becomes symptomatic or
      progressive, chemotherapy with fludarabine in combination with an anti-CD20
      antibody (FCR) is recommended as standard therapy, except for patients with
      relevant comorbidity or with del(17p13) oder TP53 mutation. We predict the number
      of prevalent CLL patients in 2011-2020 who need first-line therapy but are
      ineligible for FCR treatment. The input parameters of the Markov model are the
      estimated total CLL incidence (based on German cancer registry data) and clinical
      data on disease progression and patient characteristics (obtained by a systematic
      literature research). Plausibility ranges for the estimation of the total CLL
      incidence are given by the following: (1) inclusion of small lymphocytic lymphoma
      and (2) an alternative handling of death-certificate-only cases. The number of
      patients ineligible for FCR treatment increases from approximately 1200 in 2011
      to approximately 1450 in 2020. The inclusion of small lymphocytic lymphoma cases
      results in 10% higher estimates, the alternative handling of death-certificate
      only cases in 8% lower estimates. Recently, several new and targeted agents have
      been approved for CLL patients ineligible for standard treatment. Estimation of
      patient numbers is a prerequisite for planning of health care and for calculating
      the costs of treatment. Copyright (c) 2015 John Wiley & Sons, Ltd. 

PMID- 25757804
TI  - DNABII proteins play a central role in UPEC biofilm structure.
AB  - Most chronic and recurrent bacterial infections involve a biofilm component, the
      foundation of which is the extracellular polymeric substance (EPS). Extracellular
      DNA (eDNA) is a conserved and key component of the EPS of pathogenic biofilms.
      The DNABII protein family includes integration host factor (IHF) and histone-like
      protein (HU); both are present in the extracellular milieu. We have shown
      previously that the DNABII proteins are often found in association with eDNA and
      are critical for the structural integrity of bacterial communities that utilize
      eDNA as a matrix component. Here, we demonstrate that uropathogenic Escherichia
      coli (UPEC) strain UTI89 incorporates eDNA within its biofilm matrix and that the
      DNABII proteins are not only important for biofilm growth, but are limiting;
      exogenous addition of these proteins promotes biofilm formation that is dependent
      on eDNA. In addition, we show that both subunits of IHF, yet only one subunit of
      HU (HupB), are critical for UPEC biofilm development. We discuss the roles of
      these proteins in context of the UPEC EPS. 

PMID- 25757807
TI  - An insight into morphometric descriptors of cell shape that pertain to
      regenerative medicine.
AB  - Cellular morphology has recently been indicated as a powerful indicator of
      cellular function. The analysis of cell shape has evolved from rudimentary forms
      of microscopic visual inspection to more advanced methodologies that utilize high
      resolution microscopy coupled with sophisticated computer hardware and software
      for data analysis. Despite this progress, there is still a lack of
      standardization in quantification of morphometric parameters. In addition,
      uncertainty remains as to which methodologies and parameters of cell morphology
      will yield meaningful data, which methods should be utilized to categorize cell
      shape, and the extent of reliability of measurements and the interpretation of
      the resulting analysis. A large range of descriptors has been employed to
      objectively assess the cellular morphology in two-dimensional and three
      dimensional domains. Intuitively, simple and applicable morphometric descriptors
      are preferable and standardized protocols for cell shape analysis can be achieved
      with the help of computerized tools. In this review, cellular morphology is
      discussed as a descriptor of cellular function and the current morphometric
      parameters that are used quantitatively in two- and three-dimensional
      environments are described. Furthermore, the current problems associated with
      these morphometric measurements are addressed. Copyright (c) 2015 John Wiley &
      Sons, Ltd.

PMID- 25757805
TI  - Relationship of serum estrogens and metabolites with area and volume mammographic
      densities.
AB  - Elevated mammographic density is a breast cancer risk factor, which has a
      suggestive, but unproven, relationship with increased exposure to sex steroid
      hormones. We examined associations of serum estrogens and estrogen metabolites
      with area and novel volume mammographic density measures among 187 women, ages 40
      65, undergoing diagnostic breast biopsies at an academic facility in Vermont.
      Serum parent estrogens, estrone and estradiol, and their 2-, 4-, and 16
      hydroxylated metabolites were measured using liquid chromatography-tandem mass
      spectrometry. Area mammographic density was measured in the breast contralateral
      to the biopsy using thresholding software; volume mammographic density was
      quantified using a density phantom. Linear regression was used to estimate
      associations of estrogens with mammographic densities, adjusted for age and body
      mass index, and stratified by menopausal status and menstrual cycle phase. Weak,
      positive associations between estrogens, estrogen metabolites, and mammographic
      density were observed, primarily among postmenopausal women. Among premenopausal
      luteal phase women, the 16-pathway metabolite estriol was associated with percent
      area (p = 0.04) and volume (p = 0.05) mammographic densities and absolute area (p
      = 0.02) and volume (p = 0.05) densities. Among postmenopausal women, levels of
      total estrogens, the sum of parent estrogens, and 2-, 4- and 16-hydroxylation
      pathway metabolites were positively associated with area density measures
      (percent: p = 0.03, p = 0.04, p = 0.01, p = 0.02, p = 0.07; absolute: p = 0.02, p
      = 0.02, p = 0.01, p = 0.02, p = 0.03, respectively) but not volume density
      measures. Our data suggest that serum estrogen profiles are weak determinants of
      mammographic density and that analysis of different density metrics may provide
      complementary information about relationships of estrogen exposure to breast
      tissue composition.

PMID- 25757808
TI  - Clinical effect size of an educational intervention in the home and compliance
      with mobile phone-based reminders for people who suffer from stroke: protocol of
      a randomized controlled trial.
AB  - BACKGROUND: Stroke is the third-leading cause of death and the leading cause of
      long-term neurological disability in the world. Cognitive, communication, and
      physical weakness combined with environmental changes frequently cause changes in
      the roles, routines, and daily occupations of stroke sufferers. Educational
      intervention combines didactic and interactive intervention, which combines the
      best choices for teaching new behaviors since it involves the active
      participation of the patient in learning. Nowadays, there are many types of
      interventions or means to increase adherence to treatment. OBJECTIVE: The aim of
      this study is to enable patients who have suffered stroke and been discharged to
      their homes to improve the performance of the activities of daily living (ADL) in
      their home environment, based on advice given by the therapist. A secondary aim
      is that these patients continue the treatment through a reminder app installed on
      their mobile phones. METHODS: This study is a clinical randomized controlled
      trial. The total sample will consist of 80 adults who have suffered a stroke with
      moderate severity and who have been discharged to their homes in the 3 months
      prior to recruitment to the study. The following tests and scales will be used to
      measure the outcome variables: Barthel Index, the Functional Independence
      Measure, the Mini-Mental State Examination, the Canadian Neurological Scale, the
      Stroke Impact Scale-16, the Trunk Control Test, the Modified Rankin Scale, the
      Multidimensional Scale of Perceived Social Support, the Quality of Life Scale for
      Stroke, the Functional Reach Test, the Romberg Test, the Time Up and Go test, the
      Timed-Stands Test, a portable dynamometer, and a sociodemographic questionnaire.
      Descriptive analyses will include mean, standard deviation, and 95% confidence
      intervals of the values for each variable. The Kolmogov-Smirnov (KS) test and a
      2x2 mixed-model analysis of variance (ANOVA) will be used. Intergroup effect
      sizes will be calculated (Cohen's d). RESULTS: Currently, the study is in the
      recruitment phase and implementation of the intervention has begun. The authors
      anticipate that during 2015 the following processes should be completed:
      recruitment, intervention, and data collection. It is expected that the analysis
      of all data and the first results should be available in early-to-mid 2016.
      CONCLUSIONS: An educational intervention based on therapeutic home advice and a
      reminder app has been developed by the authors with the intention that patients
      who have suffered stroke perform the ADL more easily and use their affected limbs
      more actively in the ADL. The use of reminders via mobile phone is proposed as an
      innovative tool to increase treatment adherence in this population. TRIAL
      REGISTRATION: ClinicalTrials.gov NCT01980641;
      https://clinicaltrials.gov/ct2/show/NCT01980641 (Archived by WebCite at
      http://www.webcitation.org/6WRWFmY6U).

PMID- 25757809
TI  - Hybridized doxorubicin-Au nanospheres exhibit enhanced near-infrared surface
      plasmon absorption for photothermal therapy applications.
AB  - Photothermal therapy (PTT) employs photosensitizing agents, which are taken up by
      cells and generate heat when irradiated with near-infrared (NIR) light, to enable
      the photoablation of cancer cells. High absorption in the NIR region is crucial
      for a photosensitizing agent to achieve efficient PTT. Different combinations
      between gold nanoparticles and fluorescent agents always influence their spectrum
      properties. Herein, we fabricated a novel combination of a fluorescent agent
      (doxorubicin, DOX, also a popular chemotherapeutic agent) with gold nanospheres
      by synthesizing hybridized DOX-Au nanospheres (DAuNS), where a part of the DOX
      molecules and Au co-formed a hybridized matrix as the shell and the remaining DOX
      molecules precipitated as the core. The unique structure of DAuNS induced
      interesting changes in the characteristics including spectrum properties,
      morphology, drug loading and antitumor activity. We observed that DAuNS exhibited
      a significantly enhanced surface plasmon absorption in the NIR region, inducing a
      more efficient photothermal conversion and stronger tumor-cell killing ability
      under NIR laser irradiation. In addition, our study presents a new and simple
      platform to load a drug into nanoparticles. DAuNS could be a promising
      nanoparticle with the "two punch" efficacy of PTT and chemotherapy and could be
      used in clinical applications due to its controllable synthesis, small size, and
      narrow size distribution. 

PMID- 25757810
TI  - Multi-institution, Prospective, Randomized Trial to Compare the Success Rates of
      Single-port Versus Multiport Laparoscopic Hysterectomy for the Treatment of
      Uterine Myoma or Adenomyosis.
AB  - STUDY OBJECTIVE: To compare the operative outcomes of patients undergoing either
      single-port or multiport laparoscopic hysterectomy (LH). METHODS: Two hundred
      fifty-six women scheduled for LH for symptomatic myoma and/or adenomyosis from 8
      tertiary teaching hospitals were randomized to single-port or multiport groups.
      Primary outcome was conversion and/or complication proportion of the planned
      procedure to determine whether the success proportion of the single-port approach
      was not inferior to that of the multiport approach. Secondary outcomes were
      postoperative pain and operative scar. RESULTS: Demographic parameters including
      age, body mass index, parity, and history of vaginal and cesarean delivery were
      comparable between the 2 groups. The primary outcome of a combined conversion
      and/or complication rate was similar between the single-port and multiport groups
      at 8% and 10.3%, respectively. Conversions were similar between the groups with
      4% of single-port cases and .8% of multiport cases. Transfusions were the most
      frequent complication required in 4.0% of single-port cases and 7.9% of multiport
      cases, with no difference between the groups. Concerning secondary outcomes,
      postoperative pain score and patient and observer scar assessment were not
      different between the 2 groups. Although not a specific outcome measure, there
      was no difference between the groups in blood loss, operative time, and
      postoperative hospital stay. CONCLUSION: Single-port LH is not inferior to
      multiport LH in terms of conversion and/or complications rates, including
      transfusion. However, the single-port approach did not have any advantage over
      multiport LH with regard to pain or cosmetic outcomes. These findings were
      demonstrated by multi-institutional surgeons in Korea.

PMID- 25757811
TI  - Circulating Micro-RNAs as Diagnostic Biomarkers for Endometriosis: Privation and
      Promise.
AB  - Endometriosis represents a major medical concern in women of reproductive age.
      One of the remaining major hurdles for successful treatment of endometriosis is
      the limitation of the process of timely disease diagnosis. A simple blood test
      for endometriosis-specific biomarkers would offer a more timely accurate
      diagnosis for the disease, thus allowing for earlier treatment intervention.
      Although there have been considerable efforts to identify such biomarkers, no
      clear choice for such noninvasive diagnostic tools has been identified. Micro
      RNAs are small noncoding RNAs that have been evaluated intensively as biomarkers
      for several diseases, and they may hold promise for a diagnosis of endometriosis.
      In this review, we highlight the need for noninvasive testing for endometriosis,
      discuss the potential use of micro-RNAs as diagnostic tools for this disease, and
      consider potential limitations in the use of these small RNA molecules as
      diagnostic markers for endometriosis. 

PMID- 25757812
TI  - Contribution of Computed Tomography Enema and Magnetic Resonance Imaging to
      Diagnose Multifocal and Multicentric Bowel Lesions in Patients With Colorectal
      Endometriosis.
AB  - STUDY OBJECTIVE: To evaluate the diagnostic contribution of the computed
      tomography (CT) enema and magnetic resonance imaging (MRI) for multifocal
      (multiple lesions affecting the same segment) and multicentric (multiple lesions
      affecting several digestive segments) bowel endometriosis. DESIGN: Prospective
      cohort study (Canadian Task Force classification II-2). PATIENTS: Eighty-five
      patients. SETTING: Tenon University Hospital, Paris, France. INTERVENTION: All
      patients received a preoperative CT enema and underwent MRI interpreted by 2
      radiologists. MEASUREMENTS AND MAIN RESULTS: Patients underwent colorectal
      resection for colorectal endometriosis from February 2009 to November 2012.
      Nineteen patients (22%) had multifocal lesions, and 11 patients (13%) had
      multicentric lesions. Six patients (7%) had both multifocal and multicentric
      lesions. The sensitivity, specificity, and positive and negative likelihood
      ratios (LRs) of MRI for the diagnosis of multifocal lesions were 0.58, 0.84,
      3.55, and 0.5, respectively. The sensitivity, specificity, and positive and
      negative LRs of the CT enema for the diagnosis of multifocal lesions were 0.64,
      0.86, 4.56, and 0.4, respectively. The sensitivity, specificity, and positive LR
      of MRI for the diagnosis of multicentric lesions were 1, 0.88, and 8.4,
      respectively. The sensitivity, specificity, and positive and negative LRs of MRI
      for the diagnosis of multicentric lesions were 0.46, 0.92, 5.6, and 0.59,
      respectively. No difference was observed between MRI and the CT enema for the
      diagnosis of multifocal and multicentric colorectal endometriosis. The
      interobserver agreement was good for MRI and the CT enema (kappa = 0.45 and 0.45)
      for multifocality, and it was poor for both MRI and the CT enema (kappa = 0.32
      and 0.34) for multicentricity. CONCLUSIONS: Both MRI and the CT enema were able
      to diagnose multifocal and multicentric bowel endometriosis with similar
      accuracy.

PMID- 25757813
TI  - Resolution of Chronic Vulvar Pruritus With Replacement of a Neuromodulation
      Device.
AB  - Vulvar pruritus is typically associated with fungal, bacterial, and/or
      dermatological conditions that routinely resolve with the use of topical
      medications. Pruritus rarely becomes chronic in nature without a definable
      pathological diagnosis. However, when this occurs, management is difficult and
      has limited treatment options. Few cases have reported resolution of vulvar pain
      or discomfort with sacral neuromodulation implantation. We report a case in which
      a patient experienced chronic vulvar pruritus that was refractory to medical
      treatments and did not have a pathological diagnosis. A neurological etiology was
      suspected, and upon replacement of the patient's sacral neuromodulation device,
      complete resolution of the vulvar symptoms occurred. 

PMID- 25757814
TI  - Ovarian Suspension With Adjustable Sutures: An Easy and Helpful Technique for
      Facilitating Laparoendoscopic Single-Site Gynecologic Surgery.
AB  - STUDY OBJECTIVE: To describe a method of ovarian suspension with adjustable
      sutures (OSAS) for facilitating laparoendoscopic single-site gynecologic surgery
      (LESS) and to investigate the effect of OSAS on LESS. DESIGN: Prospective cohort
      study (Canadian Task Force classification: II-2). SETTING: University teaching
      hospital. PATIENTS: One hundred seventy-eight patients with benign 5- to 15-cm
      cystic ovarian tumors who underwent LESS with OSAS (suspension group, n = 90) and
      without OSAS (control group, n = 88). INTERVENTIONS: For patients who underwent
      OSAS (suspension group), 1 end of double-head straight needles with a
      polypropylene suture was inserted into the pelvic cavity through the abdominal
      skin to penetrate the cyst or ovarian parenchyma and puncture outside the
      abdominal skin. After cutting off the needles, both sides of the remaining suture
      were held together by a clamp, without knotting, so that the manipulator could
      "lift," "loosen," or "fix" the stitches to adjust the tension. MEASUREMENTS AND
      MAIN RESULTS: The average time to create OSAS was 2.9 min. For the suspension and
      control groups, the average blood loss was 81.4 and 131.8 mL (p < .001), and the
      operative time was 42.0 and 61.3 min (p < .001), respectively. There were no
      significant differences in the incidence of complications (5.6% vs 9.1%; p =
      .365), but there were significant differences in conversions to standard non
      single-site laparoscopy (5.6% vs 15.9%; p = .025) and laparotomy (1.1% vs 6.8%; p
      = .040). Logistic regression analysis revealed that the ratios of conversion to
      standard non-single-site laparoscopy (odds ratio [OR], 0.126; 95% confidence
      interval [CI], 0.311-0.508) and laparotomy (OR, 0.032; 95% CI, 0.002-0.479) were
      much lower in the suspension group; the risk of complications was comparable (OR,
      0.346; 95% CI, 0.085-1.403). CONCLUSION: OSAS is an easy, safe, and feasible
      method that offers advantages during LESS. Although routine use of OSAS is not
      necessary, OSAS can be considered during LESS to facilitate the surgery.

PMID- 25757815
TI  - Structural biology of antibody recognition of carbohydrate epitopes and potential
      uses for targeted cancer immunotherapies.
AB  - Monoclonal antibodies represent the most successful class of biopharmaceuticals
      for the treatment of cancer. Mechanisms of action of therapeutic antibodies are
      very diverse and reflect their ability to engage in antibody-dependent effector
      mechanisms, internalize to deliver cytotoxic payloads, and display direct effects
      on cells by lysis or by modulating the biological pathways of their target
      antigens. Importantly, one of the universal changes in cancer is glycosylation
      and carbohydrate-binding antibodies can be produced to selectively recognize
      tumor cells over normal tissues. A promising group of cell surface antibody
      targets consists of carbohydrates presented as glycolipids or glycoproteins. In
      this review, we outline the basic principles of antibody-based targeting of
      carbohydrate antigens in cancer. We also present a detailed structural view of
      antibody recognition and the conformational properties of a series of related
      tissue-blood group (Lewis) carbohydrates that are being pursued as potential
      targets of cancer immunotherapy. 

PMID- 25757817
TI  - Gas chromatography-vacuum ultraviolet spectroscopy for multiclass pesticide
      identification.
AB  - A new vacuum ultraviolet detector for gas chromatography was recently developed
      and applied to multiclass pesticide identification. VUV detection features full
      spectral acquisition in a wavelength range of 115-240nm, where virtually all
      chemical species absorb. VUV absorption spectra of 37 pesticides across different
      classes were recorded. These pesticides display rich gas phase absorption
      features across various classes. Even for isomeric compounds, such as
      hexachlorocyclohexane (HCH) isomers, the VUV absorption spectra are unique and
      can be easily differentiated. Also demonstrated is the ability to use VUV data
      analysis software for deconvolution of co-eluting signals. As a universal
      detector, VUV provides both qualitative and quantitative information. It offers
      high specificity, sensitivity (pg on-column detection limits), and a fast data
      acquisition rate, making it a powerful tool for multiclass pesticide screening
      when combined with gas chromatography. 

PMID- 25757816
TI  - Rhabdomyoblastic Differentiation in Head and Neck Malignancies Other Than
      Rhabdomyosarcoma.
AB  - Rhabdomyosarcoma is a relatively common soft tissue sarcoma that frequently
      affects children and adolescents and may involve the head and neck.
      Rhabdomyosarcoma is defined by skeletal muscle differentiation which can be
      suggested by routine histology and confirmed by immunohistochemistry for the
      skeletal muscle-specific markers myogenin or myoD1. At the same time, it must be
      remembered that when it comes to head and neck malignancies, skeletal muscle
      differentiation is not limited to rhabdomyosarcoma. A lack of awareness of this
      phenomenon could lead to misdiagnosis and, subsequently, inappropriate
      therapeutic interventions. This review focuses on malignant neoplasms of the head
      and neck other than rhabdomyosarcoma that may exhibit rhabdomyoblastic
      differentiation, with an emphasis on strategies to resolve the diagnostic
      dilemmas these tumors may present. Axiomatically, no primary central nervous
      system tumors will be discussed. 

PMID- 25757818
TI  - Schinus terebinthifolius scale-up countercurrent chromatography (Part I): High
      performance countercurrent chromatography fractionation of triterpene acids with
      off-line detection using atmospheric pressure chemical ionization mass
      spectrometry.
AB  - 'Countercurrent chromatography' (CCC) is an ideal technique for the recovery,
      purification and isolation of bioactive natural products, due to the liquid
      nature of the stationary phase, process predictability and the possibility of
      scale-up from analytical to preparative scale. In this work, a method developed
      for the fractionation of Schinus terebinthifolius Raddi berries dichloromethane
      extract was thoroughly optimized to achieve maximal throughput with minimal
      solvent and time consumption per gram of processed crude extract, using
      analytical, semi-preparative and preparative 'high performance countercurrent
      chromatography' (HPCCC) instruments. The method using the biphasic solvent system
      composed of n-heptane-ethyl acetate-methanol-water (6:1:6:1, v/v/v/v) was
      volumetrically scaled up to increase sample throughput up to 120 times, while
      maintaining separation efficiency and time. As a fast and specific detection
      alternative, the fractions collected from the CCC-separations were injected to an
      'atmospheric pressure chemical ionization mass-spectrometer' (APCI-MS/MS) and
      reconstituted molecular weight MS-chromatograms of the APCI-ionizable compounds
      from S. terebinthifolius were obtained. This procedure led to the direct
      isolation of tirucallane type triterpenes such as masticadienonic and 3beta
      masticadienolic acids. Also oleanonic and moronic acids have been identified for
      the first time in the species. In summary, this approach can be used for other
      CCC scale-up processes, enabling MS-target-guided isolation procedures. 

PMID- 25757819
TI  - Sensitive determination of glutathione in biological samples by capillary
      electrophoresis with green (515 nm) laser-induced fluorescence detection.
AB  - A new sensitive capillary electrophoretic method with laser-induced fluorescence
      (LIF) was developed for quantitation of glutathione (GSH) in biological samples.
      Eosin-5-maleimide was used to label the GSH molecule and the formed conjugate was
      separated in a 15 mM 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid
      electrolyte at pH 7.0 in less than 3 min. The conjugate was detected with an in
      house built LIF system, utilizing an inexpensive 515 nm diode laser module.
      Studies were performed to optimize the derivatization (the ratio of reagent to
      analyte, the reaction time, pH, etc.) and separation conditions. Sensitive
      detection of GSH at concentrations as low as 0.18 nM was obtained. The method was
      applied in the analysis of biological fluids (exhaled breath condensate, saliva)
      and was found to be suitable for determination of GSH in these samples at trace
      levels below 1 nM. To the best of our knowledge, this is the first report on
      determination of GSH in exhaled breath condensate by capillary electrophoresis
      (CE).

PMID- 25757820
TI  - Identification of unwanted photoproducts of cosmetic preservatives in personal
      care products under ultraviolet-light using solid-phase microextraction and micro
      matrix solid-phase dispersion.
AB  - The photochemical transformation of widely used cosmetic preservatives including
      benzoates, parabens, BHA, BHT and triclosan has been investigated in this work
      applying an innovative double-approach strategy: identification of transformation
      products in aqueous photodegradation experiments (UV-light, 254nm), followed by
      targeted screening analysis of such photoproducts in UV-irradiated cosmetic
      samples. Solid-phase microextraction (SPME) was applied, using different fiber
      coatings, in order to widen the range of detectable photoproducts in water,
      whereas UV-irradiated personal care products (PCPs) containing the target
      preservatives were extracted by micro-matrix solid-phase dispersion (micro-MSPD).
      Both SPME and micro-MSPD-based methodologies were successfully optimized and
      validated. Degradation kinetics of parent species, and photoformation of their
      transformation by-products were monitored by gas chromatography coupled to mass
      spectrometry (GC-MS). Thirty nine photoproducts were detected in aqueous
      photodegradation experiments, being tentatively identified based on their mass
      spectra. Transformation pathways between structurally related by-products,
      consistent with their kinetic behavior were postulated. The photoformation of
      unexpected photoproducts such as 2- and 4-hydroxybenzophenones, and 2,8
      dichlorodibenzo-p-dioxin in PCPs are reported in this work for the first time. 

PMID- 25757821
TI  - Grafting zwitterionic polymer onto cryogel surface enhances protein retention in
      steric exclusion chromatography on cryogel monolith.
AB  - Cryogel monoliths with interconnected macropores (10-100MUm) and hydrophilic
      surfaces can be employed as chromatography media for protein retention in steric
      exclusion chromatography (SXC). SXC is based on the principle that the exclusion
      of polyethylene glycol (PEG) on both a hydrophilic chromatography surface and a
      protein favors their association, leading to the protein retention on the
      chromatography surface. Elution of the retained protein can be achieved by
      reducing PEG concentration. In this work, the surface of polyacrylamide-based
      cryogel monolith was modified by grafting zwitterionic poly(carboxybetaine
      methacrylate) (pCBMA), leading the increase in the surface hydrophilicity.
      Observation by scanning electron microscopy revealed the presence of the grafted
      pCBMA chain clusters on the cryogel surface, but pCBMA grafting did not result in
      the changes of the physical properties of the monolith column, and the columns
      maintained good recyclability in SXC. The effect of the surface grafting on the
      SXC behavior of gamma-globulin was investigated in a wide flow rate range (0.6
      12cm/min). It was found that the dynamic retention capacity increased 1.4-1.8
      times by the zwitterionic polymer grafting in the flow rate range of 1.5
      12cm/min. The mechanism of enhanced protein retention on the zwitterionic polymer
      grafted surface was proposed. The research proved that zwitterionic polymer
      modification was promising for the development of new materials for SXC
      applications. 

PMID- 25757822
TI  - Development of amino acid derivatization reagents for liquid chromatography
      electrospray ionization mass spectrometric analysis and ionization efficiency
      measurements.
AB  - Derivatization is one of the most common ways for improving chromatographic
      separation and sensitivity for LC-ESI-MS analysis. The aim of this work was to
      design new derivatization reagents for LC-ESI-MS analysis of amino acids which
      would (1) provide good reversed phase chromatographic separation, (2) most
      importantly, provide low detection limits, (3) be easily synthesized, (4) produce
      derivatives which are less susceptible to matrix influences and (5) have
      convenient derivatization procedure with stable derivatives suitable for
      automatization. In the current work two new LC-ESI-MS compatible derivatization
      reagents have been designed and synthesized, dibenzyl ethoxymethylene malonate
      (DBEMM) and benzyl ethyl ethoxymethylene malonate (EBEMM). The DBEMM meets all
      the goals set with instrumental detection limits as low as 1 femtomole for amino
      acids and 40 attomole for selenoamino acids. 

PMID- 25757823
TI  - Ionization-based detectors for gas chromatography.
AB  - The gas phase ionization detectors are the most widely used detectors for gas
      chromatography. The column and makeup gases commonly used in gas chromatography
      are near perfect insulators. This facilitates the detection of a minute number of
      charge carriers facilitating the use of ionization mechanisms of low efficiency
      while providing high sensitivity. The main ionization mechanism discussed in this
      report are combustion in a hydrogen diffusion flame (flame ionization detector),
      surface ionization in a plasma (thermionic ionization detector), photon
      ionization (photoionization detector and pulsed discharge helium ionization
      detector), attachment of thermal electrons (electron-capture detector), and
      ionization by collision with metastable helium species (helium ionization
      detector). The design, response characteristics, response mechanism, and
      suitability for fast gas chromatography are the main features summarized in this
      report. Mass spectrometric detection and atomic emission detection, which could
      be considered as ionization detectors of a more sophisticated and complex design,
      are not discussed in this report. 

PMID- 25757824
TI  - Quantitative assessment of the degree of lipid unsaturation in intact Mortierella
      by Raman microspectroscopy.
AB  - Fungi of the genus Mortierella can accumulate large amounts of unusual lipids
      depending on species, strain, and growth conditions. Fast and easy determination
      of key parameters of lipid quality for these samples is required. In this
      contribution, we apply Raman microspectroscopy to determine the degree of
      unsaturation for fungal lipids directly inside intact hyphae without elaborate
      sample handling. Six Mortierella species were grown under varying conditions, and
      Raman spectra of single lipid vesicles were acquired. From the spectra, we
      calculate a peak intensity ratio I(1270 cm(-1))/I(1445 cm(-1)) from the signals
      of =CH and -CH2/-CH3 groups, respectively. This ratio is linked to the iodine
      value (IV) using spectra of reference compounds with known IV. IVs of fungal
      samples are compared to gas chromatography results. Values from both methods are
      in good accordance. Lipid composition is found to vary between the investigated
      species, with Mortierella alpina having the most unsaturated lipid (IV up to 280)
      and Mortierella exigua the least unsaturated (IV as low as 70). We find Raman
      microspectroscopy a suitable tool to determine the IV reliably, fast, and easily
      inside intact hyphae without extensive sample handling or treatment. The method
      can also be transferred to other microscopic samples. 

PMID- 25757825
TI  - Interpretation of FTIR spectra of polymers and Raman spectra of car paints by
      means of likelihood ratio approach supported by wavelet transform for reducing
      data dimensionality.
AB  - The problem of interpretation of common provenance of the samples within the
      infrared spectra database of polypropylene samples from car body parts and
      plastic containers as well as Raman spectra databases of blue solid and metallic
      automotive paints was under investigation. The research involved statistical
      tools such as likelihood ratio (LR) approach for expressing the evidential value
      of observed similarities and differences in the recorded spectra. Since the LR
      models can be easily proposed for databases described by a few variables,
      research focused on the problem of spectra dimensionality reduction characterised
      by more than a thousand variables. The objective of the studies was to combine
      the chemometric tools easily dealing with multidimensionality with an LR
      approach. The final variables used for LR models' construction were derived from
      the discrete wavelet transform (DWT) as a data dimensionality reduction technique
      supported by methods for variance analysis and corresponded with chemical
      information, i.e. typical absorption bands for polypropylene and peaks associated
      with pigments present in the car paints. Univariate and multivariate LR models
      were proposed, aiming at obtaining more information about the chemical structure
      of the samples. Their performance was controlled by estimating the levels of
      false positive and false negative answers and using the empirical cross entropy
      approach. The results for most of the LR models were satisfactory and enabled
      solving the stated comparison problems. The results prove that the variables
      generated from DWT preserve signal characteristic, being a sparse representation
      of the original signal by keeping its shape and relevant chemical information. 

PMID- 25757826
TI  - Classifying bivalve larvae using shell pigments identified by Raman spectroscopy.
AB  - Because bivalve larvae are difficult to identify using morphology alone, the use
      of Raman spectra to distinguish species could aid classification of larvae
      collected from the field. Raman spectra from shells of bivalve larvae exhibit
      bands that correspond to polyene pigments. This study determined if the types of
      shell pigments observed in different species could be unique enough to
      differentiate larvae using chemotaxonomic methods and cluster analysis. We
      collected Raman spectra at three wavelengths from 25 samples of bivalve larvae
      representing 16 species and four taxonomic orders. Grouping spectra within
      general categories based on order/family relationships successfully classified
      larvae with cross-validation accuracies >=92% for at least one wavelength or for
      all wavelengths combined. Classifications to species were more difficult, but
      cross-validation accuracies above 86% were observed for 7 out of 14 species when
      tested using species groups within orders/families at 785 nm. The accuracy of the
      approach likely depends on the composition of species in a sample and the species
      of interest. For example, high classification accuracies (85-98%) for
      distinguishing spectra from Crassostrea virginica larvae were achieved with a set
      of bivalve larvae occurring in the Choptank River in the Chesapeake Bay, USA,
      whereas as lower accuracies (70-92%) were found for a set of C. virginica larvae
      endemic to the Northeast, USA. In certain systems, use of Raman spectra appears
      to be a promising method for assessing the presence of certain bivalves in field
      samples and for validating high-throughput image analysis systems for larval
      bivalve studies.

PMID- 25757827
TI  - Direct immunosensing by spectral correlation interferometry: assay
      characteristics versus antibody immobilization chemistry.
AB  - A 3-channel biosensor based on spectral correlation interferometry (SCI) has been
      adapted for direct optical detection of antigens by measuring changes in
      thickness of a biolayer on functionalized glass slips employed as affordable
      single-use sensor chips. The instrument is insensitive to the bulk refractive
      index of a solution under test and provides signals in metrological units (pm or
      nm). Using real-time monitoring with the SCI, protocols for fabrication of sensor
      chips with different functional (epoxylated, carboxylated, and biotinylated)
      surfaces for antibody immobilization have been developed and optimized to
      minimize chip-to-chip variations and achieve better limit of detection (LOD),
      shorter assay time, and longer shelf life. The optimized coupling surfaces have
      been compared for detection of human serum albumin (HSA) used as a model agent of
      medical significance. The dynamic ranges for measuring the HSA concentration were
      0.07-20, 0.12-30, and 0.25-10 MUg/ml, and the assay durations were less than 20,
      15, and 30 min for the epoxylated, carboxylated, and biotinylated chips,
      respectively. The advantages of each type of sensor chip have been shown, namely,
      the carboxylated chips feature the shortest assay time, the epoxylated ones
      demonstrate the best LOD, and the biotinylated chips exhibit the longest shelf
      life in an unprotected environment. The developed protocols of antibody
      immobilization can be used in different biosensors and assay techniques including
      those based on fluorescent, magnetic or plasmonic labels, etc. The SCI is well
      compatible with various partially transparent layers used in biosensing and with
      microarrays for multi-analyte detection.

PMID- 25757828
TI  - Bilateral Subthalamic Stimulation can Improve Sleep Quality in Parkinson's
      Disease.
AB  - BACKGROUND: Sleep problems are among the most common non-motor symptoms of
      Parkinson's disease (PD). The PD Sleep Scale 2nd version (PDSS-2) improved the
      original PDSS by adding more items on different aspects of sleep problems, making
      it a more robust tool to evaluate the severity of sleep disturbances. However,
      previous studies on deep brain stimulation (DBS) have not used the PDSS-2.
      OBJECTIVE: To determine if the PDSS-2 could detect improvement reliably in sleep
      problems after bilateral subthalamic nucleus DBS for PD. METHODS: In this
      prospective study, 25 consecutive patients undergoing DBS implantation were
      enrolled. Patients were examined twice: 1 week prior to the DBS implantation
      (baseline) and 12 months postoperatively. Severity of PD symptoms were assessed
      by the Movement Disorders Society Unified PD Rating Scale (MDS-UPDRS) and the Non
      Motor Symptoms Scale (NMSS). Presence and severity of sleep disturbances were
      specifically measured by PDSS-2. RESULTS: Total score of MDS-UPDRS improved from
      81 (median, interquartile-range: 63-103) to 55 points (median, IQR: 46-75, p < 
      0.001). Health-related quality of life, measured by PDQ-39, also improved from 29
      (IQR: 18-40) to 15 (IQR: 9-28) points (p = 0.002). Most domains of NMSS also
      improved. At baseline 13 patients reported sleep problems, but 1 year after DBS
      implantation only 3 did (p = 0.012). Although only 6 out of 15 items showed a
      significant decrease after DBS implantation, the total score of PDSS-2 decreased
      from 24 (IQR: 17-32) to 10 (IQR: 7-18) points (P <  0.001). CONCLUSIONS: Based on
      our results, PDSS-2 can detect improvements in sleep quality reliably after DBS
      implantation.

PMID- 25757829
TI  - Narrative Discourse Cohesion in Early Stage Parkinson's Disease.
AB  - BACKGROUND: Models of basal ganglia (BG) function suggest that expressive
      language deficits will likely and consistently present in BG disease. Disparities
      currently exist between the predictions of models of BG function in expressive
      language and data from studies of BG disease. Traditional expressive language
      assessment methodologies that emphasize measures of language form (word and
      sentence productivity) while not carefully considering how language is used, may
      only partially account for these disparities. OBJECTIVE: To use measures of
      cohesion to examine the use of cohesive markers in narrative discourse. METHODS:
      Twelve individuals with idiopathic Parkinson's disease (PD) were compared to 12
      matched neurologically intact controls on measures of discourse performance.
      Three discourse samples (typical day, memorable vacation and family) were
      analyzed for measures of narrative productivity, number of cohesive ties and
      cohesive adequacy. Mixed model analyses were completed for group comparisons.
      RESULTS: Group differences were not observed on measures of language form as
      measured by narrative productivity, communication units, and number of cohesive
      ties produced. In contrast, group differences were observed in cohesive adequacy
      as individuals with PD produced a higher percentage of incomplete and erroneous
      cohesive ties relative the control subjects across narratives. CONCLUSIONS: These
      results support the conclusion that the BG in PD may have an executive role in
      expressive language use that can be disrupted without impacting language form.

PMID- 25757830
TI  - Role of Different Alpha-Synuclein Strains in Synucleinopathies, Similarities with
      other Neurodegenerative Diseases.
AB  - Misfolded protein aggregates are the hallmark of several neurodegenerative
      diseases in humans. The main protein constituent of these aggregates and the
      regions within the brain that are affected differ from one neurodegenerative
      disorder to another. A plethora of reports suggest that distinct diseases have in
      common the ability of protein aggregates to spread and amplify within the central
      nervous system. This review summarizes briefly what is known about the nature of
      the protein aggregates that are infectious and the reason they are toxic to
      cells. The chameleon property of polypeptides which aggregation into distinct
      high-molecular weight assemblies is associated to different diseases, in
      particular, that of alpha-synuclein which aggregation is the hallmark of distinct
      synucleinopathies, is discussed. Finally, strategies targeting the formation and
      propagation of structurally distinct alpha-synuclein assemblies associated to
      different synucleinopathies are presented and their therapeutic and diagnostic
      potential is discussed.

PMID- 25757831
TI  - Neuroimaging of Freezing of Gait.
AB  - Functional brain imaging techniques appear ideally suited to explore the
      pathophysiology of freezing of gait (FOG). In the last two decades, techniques
      based on magnetic resonance or nuclear medicine imaging have found a number of
      structural changes and functional disconnections between subcortical and cortical
      regions of the locomotor network in patients with FOG. FOG seems to be related in
      part to disruptions in the "executive-attention" network along with regional
      tissue loss including the premotor area, inferior frontal gyrus, precentral
      gyrus, the parietal and occipital areas involved in visuospatial functions of the
      right hemisphere. Several subcortical structures have been also involved in the
      etiology of FOG, principally the caudate nucleus and the locomotor centers in the
      brainstem. Maladaptive neural compensation may present transiently in the
      presence of acute conflicting motor, cognitive or emotional stimulus processing,
      thus causing acute network overload and resulting in episodic impairment of
      stepping.In this review we will summarize the state of the art of neuroimaging
      research for FOG. We will also discuss the limitations of current approaches and
      delineate the next steps of neuroimaging research to unravel the pathophysiology
      of this mysterious motor phenomenon. 

PMID- 25757833
TI  - MRCP imaging of duplicate gallbladder: a case report and review of the
      literature.
AB  - PURPOSE: Duplicate gallbladder is a rare congenital abnormality of the
      hepatobiliary system that has an incidence of roughly 1 in 4000. Many surgical
      studies have demonstrated that congenital anomalies of the gallbladder and
      anatomical variations of its position are associated with an increased risk of
      complications after laparoscopic cholecystectomy. METHODS: Using ultrasound, MRCP
      and 3D reconstructions, we report a case of a 29-year-old female who was
      incidentally revealed to have a duplicated gallbladder. A review of the
      literature surrounding this variant, its anatomical classifications and relevance
      to surgical practice is included. CONCLUSION: The double gallbladder is a rare
      congenital condition that is often not considered in the differential diagnosis
      for a patient with gallbladder disease or intraoperatively. At present, it is
      only detected via pre-operative imaging in 50% of cases, but an understanding of
      the limitations of ultrasound combined with more frequent and thorough use of
      MRCP before surgical intervention could prevent serious complications of
      laparoscopy in these patients.

PMID- 25757832
TI  - Oxidative stress, heats shock protein and histopathological effects in the gills
      of African catfish, Clarias gariepinus induced by bridge runoffs.
AB  - This study assessed the level of oxidative stress and heat shock proteins (Hsp)
      induced in gills and liver as well as the histopathological effects in the gills
      of African catfish, Clarias gariepinus, exposed to runoff water from the Third
      Mainland Bridge, the busiest bridge in the City of Lagos, Nigeria. The runoff was
      sampled off the bridge drainage, and the assessment of its physicochemical
      characteristics in both dry and rainy season indicated a high level of chemical
      and biological oxygen demand, oil and grease as well as manganese. After a
      preliminary acute toxicity evaluation, the juveniles of C. gariepinus were
      exposed to 5, 10, 15, 25, 50 and 100% runoff samples for 30 days. The level of
      the lipid peroxidation product, malondialdehyde, was significantly different from
      the control and increased serially with higher concentrations of effluent
      exposure. There was also an inhibition in the activities of enzymes, superoxide
      dismutase and catalase as well as significantly lower levels of reduced
      glutathione after 30 days. Heat shock proteins induced in the catfishes over this
      period included proteases, sHsps, Hsp 40s, Hsp 60s (for all the fishes-control
      and exposed) and Hsp 70s (in the exposed fishes only). Histopathological
      assessments of the gills indicated that the major effects of the runoff exposures
      were mild to severe thickening and fusion of the gill lamellae, stunting of
      lamellae, erosion of outer epithelium, epithelial lifting, hyperplasia, oedema
      and aneurism. The implications of the findings in the Lagos lagoon fishes were
      discussed.

PMID- 25757834
TI  - Novel clinical grading of delayed neurologic sequelae after carbon monoxide
      poisoning and factors associated with outcome.
AB  - INTRODUCTION: Delayed neurologic sequelae (DNS) after carbon monoxide (CO)
      poisoning manifest as a relapse of neurologic deficits. However, the long-term
      outcome of DNS has not been fully clarified. Myelin basic protein (MBP) levels in
      the cerebrospinal fluid (CSF) have been reported to be elevated in DNS. However,
      the precise timing and clinical value of the CSF examination have not been fully
      evaluated. We aimed to clarify the long-term outcome and the factors predicting
      the outcome of DNS and to evaluate the utility of CSF-MBP for predicting the
      development and severity of DNS. METHODS: This work was designed as a single
      center, prospective, observational study. We graded DNS severity as Grade 1
      (consistent independence), Grade 2 (temporary dependence), or Grade 3 (persistent
      dependence). We analyzed the percentage categorized in each grade and the
      parameters associated with outcome. RESULTS: Of 100 patients experiencing acute
      CO poisoning (median age: 46 years; 69% male), 20 (20%) developed DNS, including
      six Grade 1 (30%), ten Grade 2 (50%), and four Grade 3 (20%) cases. The Grade 3
      patients [median: 77 years; interquartile range (IQR): 76-82] were older than the
      Grade 1 patients [42; 30-46] (P<0.01); the DNS onset of the Grade 1 patients
      [median interval after poisoning: 35 days; IQR: 32-56] occurred later than that
      of the Grade 3 patients [10; 9-13] P<0.001) and the Grade 2 patients [25; 23-27]
      (P<0.05). The CSF-MBP levels of the DNS patients were higher than those of the
      non-DNS patients (P<0.0001). The 1-month CSF-MBP levels of the Grade 3 patients
      were higher than those of the Grade 1 patients (P<0.05); the MBP index, defined
      as [(Age)*(1-month CSF-MBP)], was higher in the Grade 3 patients than in the
      Grade 1 patients (P<0.01). Severe DNS were associated with advanced age (>72.5
      years), earlier onset (<18 days), higher 1-month CSF-MBP (>252 pg/ml), and higher
      MBP index (>20.9 year * ng/ml). CONCLUSIONS: Poor DNS outcomes were associated
      with advanced age and earlier onset. CSF-MBP can serve as a sensitive predictor
      of both the development and outcomes of DNS.

PMID- 25757836
TI  - Authors' response to van der Geest et al.

PMID- 25757835
TI  - Staphylococcal alpha-hemolysin is neurotoxic and causes lysis of brain cells in
      vivo and in vitro.
AB  - Formation of a bacterial brain abscess entails loss of brain cells and formation
      of pus. The mechanisms behind the cell loss are not fully understood.
      Staphylococcus aureus, a common cause of brain abscesses, produces various
      exotoxins, including alpha-hemolysin, which is an important factor in brain
      abscess formation. alpha-Hemolysin may cause cytolysis by forming pores in the
      plasma membrane of various eukaryotic cells. However, whether alpha-hemolysin
      causes lysis of brain cells is not known. Nor is it known whether alpha-hemolysin
      in the brain causes cell death through pore formation or by acting as a
      chemoattractant, recruiting leukocytes and causing inflammation. Here we show
      that alpha-hemolysin injected into rat brain causes cell damage and edema
      formation within 30 min. Cell damage was accompanied by an increase in
      extracellular concentrations of zinc, GABA, glutamate, and other amino acids,
      indicating plasma membrane damage, but leukocytic infiltration was not seen 0.5
      12h after alpha-hemolysin injection. This was in contrast to injection of S.
      aureus, which triggered extensive infiltration with neutrophils within 8h. In
      vitro, alpha-hemolysin caused concentration-dependent lysis of isolated nerve
      endings and cultured astrocytes. We conclude that alpha-hemolysin contributes to
      the cell death inherent in staphylococcal brain abscess formation as a pore
      forming neurotoxin.

PMID- 25757837
TI  - [Rheumatoid neutrophilic dermatitis].
AB  - The rheumatoid neutrophilic dermatitis (RND) is a rare disease associated with
      severe cases of seropositive rheumatoid arthritis (RA) seen in middle-aged
      individuals. Mostly this disease presents with erythematous papules, plaques and
      nodules. In general, RND responds either to corticosteroids or systemic treatment
      of the RA. We present the case of a 70-year-old man with RND and severe RA that
      responded to systemic corticosteroids and methotrexate. 

PMID- 25757838
TI  - Homicidal commotio cordis caused by domestic violence: A report of two cases.
AB  - Commotio cordis is a rare and fatal mechano-electric arrhythmogenic syndrome,
      occurring mainly during sports activities. The present study describes two cases
      of sudden death due to homicidal commotio cordis caused violence from an intimate
      partner. The two decedents were both young women. They suffered from physical
      abuse by their intimate partner and collapsed immediately after being punched in
      the precordium. Electrocardiograms were recorded at the hospital and showed
      ventricular fibrillation in one case. An autopsy was performed in each case, and
      no structural cardiac damage, evident lesions of other internal organs or
      underlying diseases were found. Combined with the negative toxicological
      analysis, it was concluded that the cause of death was commotio cordis due to a
      blunt force to the anterior chest. To the best of the authors' knowledge, there
      is no published report on commotio cordis caused by physical abuse from an
      intimate partner. The accurate diagnosis of the cause of death is emphasised, as
      it is important for judicial fairness. 

PMID- 25757839
TI  - Acid-free and oxone oxidant-assisted solvothermal synthesis of graphene quantum
      dots using various natural carbon materials as resources.
AB  - To prepare carbon-based fluorescent materials such as graphene quantum dots
      (GQDs), new and effective methods are needed to convert one-dimensional (1D) or
      two-dimensional (2D) carbon materials to 0D GQDs. Here, we report a novel acid
      free and oxone oxidant-assisted solvothermal synthesis of GQDs using various
      natural carbon resources including graphite (G), multiwall carbon nanotubes (M),
      carbon fibers (CF), and charcoal (C). This acid-free method, not requiring the
      neutralization process of strong acids, exhibits a simple and eco-friendly
      purification process and also represents a recycling production process, together
      with mass production and high yield. Newly synthesized GQDs exhibited a strong
      blue photoluminescence (PL) under 365 nm UV light illumination. The PL emission
      peaks of all the recycled GQDs did not change. 

PMID- 25757840
TI  - [Homozygous familial hypercholesterolaemia: Spanish adaptation of the position
      paper from the Consensus Panel on Familial Hypercholesterolaemia of the European
      Atherosclerosis Society. Consensus document of the Spanish Society of
      Arteriosclerosis (SEA) and Familial Hypercholesterolaemia Foundation (FHF)].
AB  - Homozygous familial hypercholesterolaemia (HoFH) is a rare life-threatening
      disease characterized by markedly elevated circulating levels of low-density
      lipoprotein cholesterol (LDL-C) and accelerated, premature atherosclerotic
      cardiovascular disease (ACVD). The Consensus Panel on Familial
      Hypercholesterolaemia of the European Atherosclerosis Society (EAS) has recently
      published a clinical guide to diagnose and manage HoFH (Eur Heart J. 2014;35:2146
      57). Both the Spanish Society of Atherosclerosis (SEA) and Familial
      Hypercholesterolaemia Foundation (FHF) consider this European Consensus document
      of great value and utility. However, there are particularities in our country
      which advise to have a Spanish adaptation of the European HoFH document in order
      to approximate this clinical guide to our environment. In Spain, chronic
      treatment with statins, ezetimibe and resins (colesevelam) has a reduced
      contribution in the National Health System (NHS) and is one of the few European
      countries where LDL apheresis is included in the Basic Service Portfolio
      coverage. This Spanish document also includes clinical experience in the
      management of these patients in our country. The Drafting Committee emphasizes
      the need for early identification of HoFH patients, prompt referral to
      specialized units, and an early and appropriate treatment. These recommendations
      will provide a guidance for HoFH patient management in Spain. 

PMID- 25757841
TI  - You never know where you are going until you know where you have been:
      Disorganized search after stroke.
AB  - Disorders in spatial exploration can be expressed in a disorganized fashion of
      target cancellation. There is debate regarding whether disorganized search is
      related to stroke in general, to right brain damage or to unilateral spatial
      neglect (USN) in particular. In this study, 280 stroke patients and 37 healthy
      control subjects performed a computerized shape cancellation test. We
      investigated the number of perseverations and several outcome measures regarding
      disorganized search: Consistency of search direction (best r), distance between
      consecutive cancelled targets and intersections with paths between previous
      cancelled targets. We compared performance between patients with left and right
      brain damage (L, R) and with and without USN (USN+, USN-), resulting in four
      subgroups: LUSN-, RUSN-, LUSN+, and RUSN+. Higher numbers of intersections were
      found for the left brain- and right brain-damaged patients with USN and for the
      right brain-damaged patients without USN, compared to healthy control subjects.
      Furthermore, right brain-damaged patients with USN showed a higher number of
      intersections compared to right brain-damaged patients without USN and compared
      to left brain-damaged patients with USN. To conclude, disorganized search was
      most strongly related to the neglect syndrome, and patients with more severe USN
      were even more impaired.

PMID- 25757842
TI  - Sporadic meningioangiomatosis with and without meningioma: analysis of clinical
      differences and risk factors for poor seizure outcomes.
AB  - BACKGROUND: Meningioangiomatosis (MA) is a rare cerebral lesion. Sporadic MA
      occasionally combines with meningioma (MA-M). The aim of the present study was to
      clarify whether MA-M and pure MA have clinical differences and to determine risk
      factors for unsatisfactory seizure outcomes in sporadic MA. METHODS: We reported
      14 sporadic MA cases in our center and conducted a literature review. We compared
      the demographic, clinical, imaging, electrophysiological and pathological
      features and surgical outcomes. Logistic regression analysis was performed to
      evaluate the risk factors for poor seizure outcomes. RESULTS: MA-M cases showed a
      more prominent male predilection (4.2 times vs. 1.6 times, p = 0.04), a shorter
      duration of symptoms (2.8 +/- 0.8 years vs. 5.2 +/- 0.6 years, p = 0.02), and a
      lower seizure incidence (53.6 % vs. 89.3 %, p < 0.001) as compared to pure MA. A
      gyriform alteration on imaging was exclusively associated with pure MA. The Ki-67
      was higher in the meningioma component than in the MA component in MA-M (1.2 +/-
      0.3 % vs. 6.1 +/- 1.1 %, p < 0.001). Lesions located in the temporal lobe
      predicted poor seizure outcomes (p = 0.02, OR = 4.4, 95 % confidence interval,
      1.24-15.89). CONCLUSION: Clinical differences may be caused by the different
      biological natures. MA-M seems to be a neoplastic lesion, while pure MA seems to
      be a non-neoplastic lesion. Long-term follow-up is required for MA-M. Because the
      coexistence of hippocampal sclerosis may explain the poor seizure outcomes of MA
      located in the temporal lobe, it is important to identify underlying hippocampal
      sclerosis and to perform complete resection.

PMID- 25757843
TI  - Results of treatment of unstable thoracolumbar burst fractures using pedicle
      instrumentation with and without fracture-level screws.
AB  - BACKGROUND: Two different techniques of short-segment instrumentation, with and
      without a pedicle screw at the fracture level, were compared in thoracolumbar
      burst fractures in neurologically intact (ASIA-E) patients. The sagittal index,
      kyphosis angle (Cobb), canal compromise ratio, and compression ratio of the
      anterior vertebral height were analyzed. METHODS: Seventy patients who underwent
      short-segment stabilization for thoracolumbar (T11-L2) burst fractures in our
      clinic between 2008 and 2012 were included in this retrospective study. In 35
      patients (group 1), a pedicle screw was placed only one level down and one level
      up from the fracture level. In another 35 patients (group 2), a screw was placed
      at the fracture level in addition to the short segment. Only neurologically
      intact patients with burst fractures according to the Denis classification were
      included. The patients were evaluated according to their age/gender, trauma
      etiology, and fracture level. Their preoperative and most recent postoperative
      follow-up radiographs and CTs were evaluated in terms of the sagittal index,
      kyphosis angle (Cobb), ratio of canal compromise, and anterior vertebral height.
      RESULTS: The two groups were similar in their ages, follow-up periods, and
      severity of the deformity and fracture. When the pedicle screw was placed at the
      fracture level in addition to short-segment stabilization, statistically
      significant improvements in the sagittal index (p < 0.001), local kyphosis (Cobb)
      angle (p = 0.006), and compression ratio of the anterior vertebral height (p =
      0.002) were observed. Concerning the ratio of canal compromise according to the
      CT findings (p = 0.189), moderate differences were found. CONCLUSIONS: Short
      segment stabilization in thoracolumbar burst fractures with additional screws at
      the level of the fracture results in an improved kyphosis correction, sagittal
      index, and compression ratio of the anterior vertebral height. However, long-term
      follow-up is needed to determine the clinical significance of these findings.

PMID- 25757844
TI  - Health literacy as a process: caseworker perspectives on HIV health literacy.
AB  - Health status and health literacy are interrelated. Previous research suggests
      that this relationship must be considered when providing services to HIV positive
      individuals. However, the pathways through which health literacy affects HIV
      remain unclear. This study seeks to understand the connections between health
      literacy and HIV from a caseworker perspective. Results suggest that caseworkers
      reject static definitions of health literacy by conceptualizing it as an emergent
      process. Caseworkers also expressed the need for development of subcomponents
      upon which health literacy is founded: (a) the building of trust, and (b)
      understanding clients' hierarchy of needs. 

PMID- 25757845
TI  - A new HLA-A*26 family allele--HLA-A*26:103.
AB  - HLA-A*26:103 differs from A*26:01:01 by one base (559C>G) in exon 3 resulting in
      an amino acid substitution of R163G. 

PMID- 25757846
TI  - Lessons on humanity and humility in the Appalachian Mountains.

PMID- 25757847
TI  - The still point of the turning world? Building on Balint: A personal view.
AB  - In this article, I will respond to the conference title "Building on Balint" by
      briefly considering some of the inherent obstacles to Balint work, before
      describing the current state of play in the UK. I will argue that Balint work
      might benefit from exploring its relationship with attachment theory more fully.
      In particular, I emphasize an important new role for Balint groups within
      contemporary health-care organizations-one that enhances a feeling of emotional
      security for the professional within the organization and also benefits the
      teamwork and morale of the organization itself. I will give an example of a
      Balint group in a health-care organization for vulnerable doctors and finish by
      giving a report on the development of Balint groups for medical students in the
      UK. 

PMID- 25757848
TI  - The sadness connection.

PMID- 25757849
TI  - 14 days.

PMID- 25757850
TI  - A life of real sweetness.

PMID- 25757851
TI  - Incidence of secondary malignancies among patients with Waldenstrom
      macroglobulinemia: An analysis of the SEER database.
AB  - BACKGROUND: Waldenstrom macroglobulinemia (WM) is an indolent malignancy that
      predominantly affects older individuals who are at risk for secondary
      malignancies (SMs). The objective of this study was to characterize the incidence
      of SMs after a diagnosis of WM with the Surveillance, Epidemiology, and End
      Results (SEER) database. METHODS: With SEER-13 data (1992-2011), standardized
      incidence ratios (SIRs) and 95% confidence intervals (CIs) were calculated for
      the rates of solid and hematologic SMs in WM patients versus the general
      population. The analysis was stratified by age, sex, race, year of diagnosis, and
      latency from the WM diagnosis. RESULTS: Among 4676 patients with WM, 681 SMs were
      recorded. The overall SIR was 1.49 (95% CI, 1.38-1.61), and the median time to an
      SM was 3.7 years. The cumulative incidence of SMs was 10% at 5 years and 16% at
      10 years. The risk was significantly increased for cancers of the lungs, urinary
      tract, and thyroid; melanoma; aggressive lymphoma; and acute leukemia. The SIR
      for SMs in patients with WM was increased, regardless of age, sex, race, or year
      of diagnosis. CONCLUSIONS: Patients with WM had a 49% higher risk of SMs than the
      general population. The selectively increased risk for hematologic SMs and
      certain solid SMs may be associated with transformation, therapy, and immune
      dysregulation.

PMID- 25757852
TI  - Evolution of an ancient venom: recognition of a novel family of cnidarian toxins
      and the common evolutionary origin of sodium and potassium neurotoxins in sea
      anemone.
AB  - Despite Cnidaria (sea anemones, corals, jellyfish, and hydroids) being the oldest
      venomous animal lineage, structure-function relationships, phyletic
      distributions, and the molecular evolutionary regimes of toxins encoded by these
      intriguing animals are poorly understood. Hence, we have comprehensively
      elucidated the phylogenetic and molecular evolutionary histories of
      pharmacologically characterized cnidarian toxin families, including peptide
      neurotoxins (voltage-gated Na(+) and K(+) channel-targeting toxins: NaTxs and
      KTxs, respectively), pore-forming toxins (actinoporins, aerolysin-related toxins,
      and jellyfish toxins), and the newly discovered small cysteine-rich peptides
      (SCRiPs). We show that despite long evolutionary histories, most cnidarian toxins
      remain conserved under the strong influence of negative selection-a finding that
      is in striking contrast to the rapid evolution of toxin families in
      evolutionarily younger lineages, such as cone snails and advanced snakes. In
      contrast to the previous suggestions that implicated SCRiPs in the
      biomineralization process in corals, we demonstrate that they are potent
      neurotoxins that are likely involved in the envenoming function, and thus
      represent the first family of neurotoxins from corals. We also demonstrate the
      common evolutionary origin of type III KTxs and NaTxs in sea anemones. We show
      that type III KTxs have evolved from NaTxs under the regime of positive
      selection, and likely represent a unique evolutionary innovation of the
      Actinioidea lineage. We report a correlation between the accumulation of
      episodically adaptive sites and the emergence of novel pharmacological activities
      in this rapidly evolving neurotoxic clade. 

PMID- 25757853
TI  - Synthesis of dibenzothiophene-based host materials with a dimesitylborane
      substituent and their green PHOLED performances.
AB  - In the two isomeric dibenzothiophene-based host materials, the different linkages
      between dibenzothiophene and dimesitylborane on a phenyl spacer dictated their
      photophysical properties. The performances of Ir(ppy)2(acac)-based green
      phosphorescent devices with two isomeric host materials were similar regardless
      of different linkage positions. 

PMID- 25757855
TI  - Impact of a Shared Medical Appointment Lifestyle Intervention on Weight and Lipid
      Parameters in Individuals with Type 2 Diabetes: A Clinical Pilot.
AB  - BACKGROUND: There is a growing awareness that lifestyle behavior modifications
      may reduce weight and the atherogenic dyslipidemia associated with obesity and
      type 2 diabetes mellitus (T2DM). OBJECTIVE: We pilot the effectiveness of a
      diabetes educational program combining shared medical appointments (SMAs) with an
      8-week DVD-based diabetes education program emphasizing a plant-based diet in
      lowering weight and lipids in individuals with T2DM. This pilot also employed a
      nonrandomized convenience sample to explore which of the educational program's
      target behaviors were associated with the greatest risk factor reduction. DESIGN:
      Forty-six adult patients with T2DM voluntarily self-selected to enroll in the
      educational quality improvement initiative run as part of a community clinical
      practice. Target behaviors measured weekly were (1) days with beans for
      breakfast, (2) days of exercise, (3) minutes of exercise per day, (4) days with
      light evening meals, (5) days with no evening meals, (6) days with no red meat,
      (7) days with plant-based diet, and (8) number of 8-ounce cups of water per day.
      Biometric measurements were taken at the beginning and end of the 2-month
      program. These included high-density lipoprotein (HDL), low-density lipoprotein
      (LDL), total cholesterol, and triglycerides. Weight was measured weekly.
      Regression analysis was performed to identify which target behaviors were
      associated with changes in lipids and weight. RESULTS: There was a statistically
      significant (F = 2.429; df = 8.21; p < 0.05) decrease in weight (mean -8.9 lbs,
      or 4.05 kg, or 4.1% body weight, p < 0.01) during the 8-week study period. There
      was a positive trend in all lipid parameters, but none reached statistical
      significance with this sample. Exploratory weighted least-squares regression
      found that weight loss in the study group was most associated with higher water
      consumption (t = 3.16; p < 0.01), days per week with no evening meal (t = 3.03; p
      < 0.01), and days per week consuming beans for breakfast (t = 2.06; p = 0.05.
      CONCLUSIONS: In this pilot study, the DVD-based educational program delivered as
      part of an SMA was associated with significant weight loss but insignificant
      lipid changes. Behavior changes most closely associated with weight loss were
      increasing water consumption, eliminating evening meals, and increasing the
      consumption of beans for breakfast. These potentially important findings in this
      small sample suggest the need for a randomized clinical trial with a larger and
      planned sample.

PMID- 25757854
TI  - Clinical characteristics and prognostic factors of adult hemophagocytic syndrome
      patients: a retrospective study of increasing awareness of a disease from a
      single-center in China.
AB  - BACKGROUND: Hemophagocytic lymphohistiocytosis (HLH) is a relatively rare but
      life-threatening disease with confusing clinical manifestations, rapidly
      deteriorating health, high morbidity and mortality. METHODS: To improve the
      recognition as well as understanding of this disorder, we analyzed clinical
      characteristics and prognostic factors from 85 adult patients diagnosed with HLH
      in our hospital from April 2005 to June 2014. RESULTS: Patients with HLH
      displayed variable clinical markers across a wide spectrum. These included fever
      and hyperferritinemia (100%), elevated lactate dehydrogenase (LDH) (98.8%), two
      or three cytopenia (92.2%), splenomegaly (72.9%), hypofibrinogenemia (69.4%),
      hypertriglyceridemia (64.7%), hemophagocytosis (51.7%), and hepatomegaly (24.7%).
      Patients with active Epstien-Barr Virus (EBV) infection had a median overall
      survival (OS) of 65 days. Those displaying malignancy had very poor survival
      (median OS: 40 days). However, patients in rheumatic and non-EBV infection groups
      had relatively superior prognosis (not reached). Univariate analysis showed that
      Fibrinogen (Fbg) <1.5 g/L, platelet number (PLT) <40 * 10(9)/L and LDH >=1000 U/L
      were factors that negatively affected survival (P = 0.004, 0.000, 0.002).
      Multivariate analysis showed that PLT <40 * 10(9)/L was the independent adverse
      factor (HR = 0.350, 95% CI: 0.145-0.844, P = 0.019). CONCLUSIONS: HLH had very
      complex clinical manifestations and high death rate. Patients with active EBV
      infection, malignancy, Fbg <1.5 g/L, PLT <40 * 10(9)/L and LDH >=1000 U/L had
      high risk of death as well as inferior survival, and these patients require
      systemic targeted treatments as early as possible.

PMID- 25757856
TI  - Label-free detection and characterization of the binding of hemagglutinin protein
      and broadly neutralizing monoclonal antibodies using terahertz spectroscopy.
AB  - Hemagglutinin (HA) is the main surface glycoprotein of the influenza A virus. The
      H9N2 subtype influenza A virus is recognized as the most possible pandemic strain
      as it has crossed the species barrier, infecting swine and humans. We use
      terahertz spectroscopy to study the hydration shell formation around H9 subtype
      influenza A virus's HA protein (H9 HA) as well as the detection of antigen
      binding of H9 HA with the broadly neutralizing monoclonal antibody. We observe a
      remarkable concentration dependent nonlinear response of the H9 HA, which reveals
      the formation process of the hydration shell around H9 HA molecules. Furthermore,
      we show that terahertz dielectric properties of the H9 HA are strongly affected
      by the presence of the monoclonal antibody F10 and that the terahertz dielectric
      loss tangent can be used to detect the antibody binding at lower concentrations
      than the standard ELISA test.

PMID- 25757857
TI  - Implementing change: staff experiences of changes to prison mental healthcare in
      England and Wales.
AB  - PURPOSE: Stemming from substantial criticism during the late twentieth and early
      twenty-first century, the UK government and HM Prison Service developed a number
      of policies and protocols aimed at improving the state of prison mental
      healthcare. While it is difficult to fault the purpose of the government's
      intentions, criticism has continued relating to problems with the implementation
      of government led change within the prison system. Existing research leads people
      to question whether policies are being implemented as intended; and if not, why
      not? The only clear way to answer these questions is to ask those involved in the
      actual implementation of these recommendations within the prison service. This
      paper aims to answer these questions. DESIGN/METHODOLOGY/APPROACH: This paper
      documents findings from a national survey of senior mental healthcare staff
      working in prisons in England and Wales. Staff were surveyed about their views on
      the implementation of recommendations from recent key government documents, their
      perceptions of prison mental healthcare versus community mental healthcare, and
      their views on the relationship between HM Prison Service and the National Health
      Service. FINDINGS: While many staff report improvements in prison mental
      healthcare, many have struggled with the implementation of new ways of working
      and the findings here suggest there is still some way to go towards providing
      offenders in prison with effective and appropriate care. Where effective ways of
      implementing change were identified, these are discussed. ORIGINALITY/VALUE:
      Listening to the experiences of the staff involved in prison healthcare has
      helped identify where implementation of changes could be improved and thus
      highlights where support might best be targeted in future.

PMID- 25757858
TI  - Toward healthy prisons: the TECH model and its applications.
AB  - PURPOSE: This paper aims to explore how the TECH Model (testing for and treating
      infectious diseases and vaccination; environmental modification to prevent
      disease transmission; chronic disease identification and treatment; and health
      maintenance and education) can be used for assessing and achieving healthy
      prisons. DESIGN/METHODOLOGY/APPROACH: This paper explores the concepts of "health
      in prison" and "healthy prisons" in the context of recent research and guidance.
      The paper then considers the TECH Model as an approach to achieving healthy
      prisons. FINDINGS: Under each of the four TECH Model domains are tasks to achieve
      a healthy prison. For prisons with poor or no resources, each domain contains
      steps that will improve prison health and move towards a healthy prison for both
      prisoners and staff. Implementation can thus be "low-TECH" or "high-TECH"
      depending on the setting and the available resources and the model is
      specifically designed to provide options for resource-poor as well as resource
      rich correctional settings. ORIGINALITY/VALUE: The TECH Model is a first step in
      characterizing the components of a healthy prison and the processes to achieve
      this. This Model could be implemented in all levels of prisons internationally.

PMID- 25757859
TI  - Dentition status and treatment needs of prisoners of Haryana state, India.
AB  - PURPOSE: This paper aims to explore prisoner dental health in Haryana, India.
      DESIGN/METHODOLOGY/APPROACH: The authors assessed the prevalence of dental caries
      and the treatment needs of prisoners in all 19 prisons in Haryana. The results
      were compared with the prison populations of other countries and the general
      population of Haryana. FINDINGS: The mean age of 1,393 subjects examined was
      35.26+/-12.29 years. A large number of the subjects reported to be in need of
      dental treatment. The number of decayed teeth was found to be similar to the
      general population of Haryana but the number of filled teeth was quite low. The
      number of teeth missing and the need for tooth extraction was high. Social
      implications - Long-standing prisoner dental problems indicated a need for dental
      treatment in prisons. ORIGINALITY/VALUE: This is the first study of its kind
      covering all 19 prisons in Haryana, India. The results indicate that the
      government needs to further consider and address the oral health needs of
      prisoners.

PMID- 25757860
TI  - "Double burden": a qualitative study of HIV positive prisoners in Italy.
AB  - PURPOSE: This paper aims to consider the influence of imprisonment on the health
      of prisoners with the HIV virus or AIDS and their perceptions of their quality of
      life. DESIGN/METHODOLOGY/APPROACH: This is a qualitative study involving adult
      male prisoners in three Italian prisons. A total of 19 individual semi-structured
      interviews were conducted. FINDINGS: Life in prison for HIV positive detainees is
      experienced as a kind of "double burden," due to the connection between the loss
      of freedom and the limitations imposed by their health status. The experience of
      being ill and sick in prison results in the prisoner exhibiting fatalism towards
      the future, having a sense of alienation and marginalisation as well as being
      afraid of the consequences of living with HIV or AIDS. SOCIAL IMPLICATIONS:
      Prison can be considered as a "total institution" where prisoners are cut off
      from every role except the negative one of a prisoner deprived of freedom, and
      this situation greatly contributes to apathy and reinforces the inmates'
      antisocial behaviour. Originality/value - This paper gives a voice to the needs
      and views of Italian prisoners who are HIV positive or who have AIDS and presents
      these in the context of the international situation.

PMID- 25757861
TI  - Construction of a hemifullerene skeleton: a regioselective intramolecular
      oxidative cyclization.
AB  - A two-step synthesis of a strained pi bowl, with hemifullerene skeleton from
      sumanene, was achieved in a high yield. The first step is a base-promoted
      condensation reaction with a benzophenone compound, bis(3,5
      dimethylphenyl)methanone. The second step is the regioselective intramolecular
      oxidative cyclization, which is a key reaction for the hemifullerene skeleton
      synthesis. This regioselective cyclization is likely to be under thermodynamic
      control. This strategy will allow facile synthesis of various highly strained pi
      bowls. 

PMID- 25757862
TI  - Involvement of prostaglandin E2 in the first Japanese case of
      pachydermoperiostosis with HPGD mutation and recalcitrant leg ulcer.

PMID- 25757863
TI  - New avenues for phase matching in nonlinear hyperbolic metamaterials.
AB  - Nonlinear optical processes, which are of paramount importance in science and
      technology, involve the generation of new frequencies. This requires phase
      matching to avoid that light generated at different positions interferes
      destructively. Of the two original approaches to achieve this, one relies on
      birefringence in optical crystals, and is therefore limited by the dispersion of
      naturally occurring materials, whereas the other, quasi-phase-matching, requires
      direct modulation of material properties, which is not universally possible. To
      overcome these limitations, we propose to exploit the unique dispersion afforded
      by hyperbolic metamaterials, where the refractive index can be arbitrarily large.
      We systematically analyse the ensuing opportunities and demonstrate that
      hyperbolic phase matching can be achieved with a wide range of material
      parameters, offering access to the use of nonlinear media for which phase
      matching cannot be achieved by other means. With the rapid development in the
      fabrication of hyperbolic metamaterials, our approach is destined to bring
      significant advantages over conventional techniques for the phase matching of a
      variety of nonlinear processes. 

PMID- 25757864
TI  - Silane-catalysed fast growth of large single-crystalline graphene on hexagonal
      boron nitride.
AB  - The direct growth of high-quality, large single-crystalline domains of graphene
      on a dielectric substrate is of vital importance for applications in electronics
      and optoelectronics. Traditionally, graphene domains grown on dielectrics are
      typically only ~1 MUm with a growth rate of ~1 nm min(-1) or less, the main
      reason is the lack of a catalyst. Here we show that silane, serving as a gaseous
      catalyst, is able to boost the graphene growth rate to ~1 MUm min(-1), thereby
      promoting graphene domains up to 20 MUm in size to be synthesized via chemical
      vapour deposition (CVD) on hexagonal boron nitride (h-BN). Hall measurements show
      that the mobility of the sample reaches 20,000 cm(2) V(-1) s(-1) at room
      temperature, which is among the best for CVD-grown graphene. Combining the
      advantages of both catalytic CVD and the ultra-flat dielectric substrate, gaseous
      catalyst-assisted CVD paves the way for synthesizing high-quality graphene for
      device applications while avoiding the transfer process. 

PMID- 25757866
TI  - Cancer researcher fails in court bid to unmask online critics.

PMID- 25757865
TI  - Adult weight gain and adiposity-related cancers: a dose-response meta-analysis of
      prospective observational studies.
AB  - BACKGROUND: Adiposity, measured by body mass index, is implicated in
      carcinogenesis. While adult weight gain has diverse advantages over body mass
      index in measuring adiposity, systematic reviews on adult weight gain in relation
      to adiposity-related cancers are lacking. METHODS: PubMed and Embase were
      searched through September 2014 for prospective observational studies
      investigating the relationship between adult weight gain and the risk of 10
      adiposity-related cancers. Dose-response meta-analyses were performed using a
      random-effects model to estimate summary relative risk (RR) and 95% confidence
      interval (CI) for each cancer type. All statistical tests were two-sided.
      RESULTS: A total of 50 studies were included. For each 5 kg increase in adult
      weight gain, the summary relative risk was 1.11 (95% CI = 1.08 to 1.13) for
      postmenopausal breast cancer among no- or low-hormone replacement therapy (HRT)
      users, 1.39 (95% CI = 1.29 to 1.49) and 1.09 (95% CI = 1.02 to 1.16) for
      postmenopausal endometrial cancer among HRT nonusers and users, respectively,
      1.13 (95% CI = 1.03 to 1.23) for postmenopausal ovarian cancer among no or low
      HRT users, 1.09 (95% CI = 1.04 to 1.13) for colon cancer in men. The relative
      risk of kidney cancer comparing highest and lowest level of adult weight gain was
      1.42 (95% CI = 1.11 to 1.81). Adult weight gain was unrelated to cancers of the
      breast (premenopausal women, postmenopausal HRT users), prostate, colon (women),
      pancreas, and thyroid. An increase in risk associated with adult weight gain for
      breast cancer was statistically significantly greater among postmenopausal women
      (P(heterogeneity) = .001) and HRT nonusers (P(heterogeneity) = .001); that for
      endometrial cancer was alike among HRT nonusers (P(heterogeneity) = .04).
      CONCLUSIONS: Avoiding adult weight gain itself may confer protection against
      certain types of cancers, particularly among HRT nonusers.

PMID- 25757868
TI  - Concerns about report suggesting glucosamine and chondroitin protect against
      cartilage loss.

PMID- 25757867
TI  - Long-term follow-up of the MAINTAIN Nephritis Trial, comparing azathioprine and
      mycophenolate mofetil as maintenance therapy of lupus nephritis.
AB  - OBJECTIVE: To report the 10-year follow-up of the MAINTAIN Nephritis Trial
      comparing azathioprine (AZA) and mycophenolate mofetil (MMF) as maintenance
      therapy of proliferative lupus nephritis, and to test different definitions of
      early response as predictors of long-term renal outcome. METHODS: In 2014, data
      on survival, kidney function, 24 h proteinuria, renal flares and other outcomes
      were collected for the 105 patients randomised between 2002 and 2006, except in
      13 lost to follow-up. RESULTS: Death (2 and 3 in the AZA and MMF groups,
      respectively) and end-stage renal disease (1 and 3, respectively) were rare
      events. Time to renal flare (22 and 19 flares in AZA and MMF groups,
      respectively) did not differ between AZA and MMF patients. Patients with good
      long-term renal outcome had a much more stringent early decrease of 24 h
      proteinuria compared with patients with poor outcome. The positive predictive
      value of a 24 h proteinuria <0.5 g/day at 3 months, 6 months and 12 months for a
      good long-term renal outcome was excellent (between 89% and 92%). Inclusion of
      renal function and urinalysis in the early response criteria did not impact the
      value of early proteinuria decrease as long-term prognostic marker. CONCLUSIONS:
      The long-term follow-up data of the MAINTAIN Nephritis Trial do not indicate that
      MMF is superior to AZA as maintenance therapy in a Caucasian population suffering
      from proliferative lupus nephritis. Moreover, we confirm the excellent positive
      predictive value of an early proteinuria decrease for long-term renal outcome.
      TRIAL REGISTRATION NUMBER: NCT00204022.

PMID- 25757869
TI  - The therapeutic window of opportunity in rheumatoid arthritis: does it ever
      close?

PMID- 25757870
TI  - Immediate loading short implants inserted on low bone quantity for the
      rehabilitation of the edentulous maxilla using an All-on-4 design.
AB  - More studies evaluating the outcome of short-length dental implants in immediate
      loading are needed. To evaluate the use of short-length tapered implants in
      immediate loading for complete edentulous maxillae rehabilitations using an All
      on-4 design. This retrospective clinical study included a cohort of 43 patients
      with 172 implants (74 short-length implants) inserted in low bone quantity. The
      patients were followed between 4 months and 6 years (average = 3 years). Outcome
      measures were implant survival, marginal bone remodelling, biological and
      mechanical complications. Two patients with four short-length implants were lost
      to follow-up during the first year. Three short and three long implants failed in
      four patients, rendering an overall cumulative survival rate implant and patient
      level, respectively, of 95.7% and 95.1% for short implants, 100% for regular
      implants and 96.6% and 95.2% for long implants. The average marginal bone
      remodelling at 1 and 3 years was 0.97 and 1.25 mm for the short implants, 0.82
      and 0.87 mm for regular implants and 0.87 and 0.98 mm for long implants. Three
      patients presented 4 short-length implants with peri-implant pockets (3 implants
      in 2 patients were pseudo-pockets). Mechanical complications were registered in
      13 patients (7 provisional prostheses fractures and 6 abutment screw loosening).
      All complications were treated successfully. Within the limitations of this
      clinical study, the short-term outcome of fixed prosthetic complete edentulous
      maxillae rehabilitations supported by short-length implants inserted in low bone
      quantity areas is viable. Long-term clinical studies are necessary for evaluating
      the outcome of these implants.

PMID- 25757871
TI  - Meso/macroporous nitrogen-doped carbon architectures with iron carbide
      encapsulated in graphitic layers as an efficient and robust catalyst for the
      oxygen reduction reaction in both acidic and alkaline solutions.
AB  - Meso-/macroporous nitrogen-doped carbon architectures with iron carbide
      encapsulated in graphitic layers are fabricated by a facile approach. This
      efficient and robust material exhibits superior catalytic performance toward the
      oxygen reduction reaction in both acidic and alkaline solutions and is the most
      promising alternative to a Pt catalyst for use in electrochemical energy devices.

PMID- 25757872
TI  - Application of a high-throughput relative chemical stability assay to screen
      therapeutic protein formulations by assessment of conformational stability and
      correlation to aggregation propensity.
AB  - In this study, an automated high-throughput relative chemical stability (RCS)
      assay was developed in which various therapeutic proteins were assessed to
      determine stability based on the resistance to denaturation post introduction to
      a chaotrope titration. Detection mechanisms of both intrinsic fluorescence and
      near UV circular dichroism (near-UV CD) are demonstrated. Assay robustness was
      investigated by comparing multiple independent assays and achieving r(2) values
      >0.95 for curve overlays. The complete reversibility of the assay was
      demonstrated by intrinsic fluorescence, near-UV CD, and biologic potency. To
      highlight the method utility, we compared the RCS assay with differential
      scanning calorimetry and dynamic scanning fluorimetry methodologies. Utilizing
      C1/2 values obtained from the RCS assay, formulation rank-ordering of 12
      different mAb formulations was performed. The prediction of long-term stability
      on protein aggregation is obtained by demonstrating a good correlation with an
      r(2) of 0.83 between RCS and empirical aggregation propensity data. RCS promises
      to be an extremely useful tool to aid in candidate formulation development
      efforts based on the complete reversibility of the method to allow for multiple
      assessments without protein loss and the strong correlation between the C1/2 data
      obtained and accelerated stability under stressed conditions.

PMID- 25757873
TI  - Echocardiographic quantification of left ventricular systolic function.

PMID- 25757874
TI  - A two-photon fluorescent probe for detecting endogenous hypochlorite in living
      cells.
AB  - A novel two-photon fluorescent probe () for hypochlorite (ClO(-)) has been
      developed based on specific ClO(-)-promoted oxidation of a C[double bond, length
      as m-dash]N bond. The probe shows linear fluorescence responses to ClO(-) with
      23.5-fold enhancement. Two-photon fluorescence detection signals of to ClO(-)
      were observed with high selectivity and sensitivity. The good biocompatibility
      guaranteed the use of to detect intracellular ClO(-) under two-photon excitation.
      Moreover, has been successfully applied to monitor the endogenously produced
      hypochlorite in living cells (BV-2) stimulated by lipopolysaccharide (LPS).
      provides a new ClO(-) detection agent for the discovery of pharmacological
      microglia modulators by high-throughput screening. 

PMID- 25757875
TI  - Does response selection contribute to inhibition of return?
AB  - Inhibition of return (IOR) means delayed responses for targets at a cued compared
      to targets at an uncued location. It is assumed to reflect delayed reallocation
      of attention toward a previously attended location. Besides an attentional
      mechanism, IOR could also be due to a cue-evoked inhibition to respond toward a
      cued target. In the present study, IOR with simple, compatible, and incompatible
      choice responses was compared and tracked by means of event-related EEG activity.
      IOR was amplified with simple responses but did not differ between compatible and
      incompatible responses. Attention-related ERP correlates were constant across cue
      target onset asynchronies as were, in part, behavioral effects. Early, rather
      sensory ERP components varied with time, reflecting sensory or attentional
      interaction of cue and target processing. None of these effects varied with
      response requirements, indicating that response selection does not contribute to
      IOR in manual choice response tasks. 

PMID- 25757876
TI  - Rapid detection of genetic mutations in individual breast cancer patients by next
      generation DNA sequencing.
AB  - Breast cancer is the most common malignancy in women and the leading cause of
      cancer deaths in women worldwide. Breast cancers are heterogenous and exist in
      many different subtypes (luminal A, luminal B, triple negative, and human
      epidermal growth factor receptor 2 (HER2) overexpressing), and each subtype
      displays distinct characteristics, responses to treatment, and patient outcomes.
      In addition to varying immunohistochemical properties, each subtype contains a
      distinct gene mutation profile which has yet to be fully defined. Patient
      treatment is currently guided by hormone receptor status and HER2 expression, but
      accumulating evidence suggests that genetic mutations also influence drug
      responses and patient survival. Thus, identifying the unique gene mutation
      pattern in each breast cancer subtype will further improve personalized treatment
      and outcomes for breast cancer patients. In this study, we used the Ion Personal
      Genome Machine (PGM) and Ion Torrent AmpliSeq Cancer Panel to sequence 737
      mutational hotspot regions from 45 cancer-related genes to identify genetic
      mutations in 80 breast cancer samples of various subtypes from Chinese patients.
      Analysis revealed frequent missense and combination mutations in PIK3CA and TP53,
      infrequent mutations in PTEN, and uncommon combination mutations in luminal-type
      cancers in other genes including BRAF, GNAS, IDH1, and KRAS. This study
      demonstrates the feasibility of using Ion Torrent sequencing technology to
      reliably detect gene mutations in a clinical setting in order to guide
      personalized drug treatments or combination therapies to ultimately target
      individual, breast cancer-specific mutations. 

PMID- 25757878
TI  - Molecular mechanisms of drug resistance and its reversal in cancer.
AB  - Chemotherapy is the main strategy for the treatment of cancer. However, the main
      problem limiting the success of chemotherapy is the development of multidrug
      resistance. The resistance can be intrinsic or acquired. The resistance phenotype
      is associated with the tumor cells that gain a cross-resistance to a large range
      of drugs that are structurally and functionally different. Multidrug resistance
      arises via many unrelated mechanisms, such as overexpression of energy-dependent
      efflux proteins, decrease in uptake of the agents, increase or alteration in drug
      targets, modification of cell cycle checkpoints, inactivation of the agents,
      compartmentalization of the agents, inhibition of apoptosis and aberrant
      bioactive sphingolipid metabolism. Exact elucidation of resistance mechanisms and
      molecular and biochemical approaches to overcome multidrug resistance have been a
      major goal in cancer research. This review comprises the mechanisms guiding
      multidrug resistance in cancer chemotherapy and also touches on approaches for
      reversing the resistance. 

PMID- 25757877
TI  - Immune therapies in non-muscle invasive bladder cancer.
AB  - OPINION STATEMENT: Non-muscle invasive bladder cancer (NMIBC) continues to be a
      challenging disease to manage. Treatment involves transurethral resection and,
      often, intravesical therapy. Appropriate patient selection, accurate staging, and
      morphological characterization are vital in risk-stratifying patients to those
      who would most benefit from receiving intravesical therapy. Bacillus of Calmette
      and Guerin (BCG) continues to be the first-line agent of choice for patients with
      intermediate- and high-risk NMIBC. Treatment should begin with the standard
      induction course of 6 weekly treatments. The inclusion of subsequent maintenance
      courses of BCG is imperative to optimal therapeutic response. While patients with
      intermediate-risk disease should receive 1 year of maintenance therapy, high-risk
      patients benefit from up to 3 years of maintenance therapy. BCG use should not be
      used in low-risk patients with de novo Ta, low-grade, solitary, <3-cm tumors.
      Conversely, patients with muscle-invasive disease should forgo intravesical
      immunotherapy and proceed directly to radical cystectomy. Cystectomy also should
      be considered in patients with multiple T1 tumors, T1 tumors located in difficult
      to resect locations, residual T1 on re-resection, and T1 with concomitant CIS.
      Although promising new immunotherapeutic agents, such as Urocidin, protein-based
      vaccines, and immune check point inhibitors are undergoing preclinical and
      clinical investigation, immunotherapy in bladder cancer remains largely reliant
      on intravesical BCG with surgical consolidation as the standard salvage treatment
      for patients with BCG failure.

PMID- 25757879
TI  - Effect of protein and energy levels in sweet sorghum bagasse leaf residue-based
      diets on the performance of growing Deccani lambs.
AB  - Sweet sorghum bagasse with leaf residue (SSBLR) based complete diets with high or
      low protein and high- or low-energy levels were evaluated in a 60-day growth
      trial using growing sheep. Twenty-eight Deccani ram lambs were divided into four
      groups (16.0 +/- 0.59 kg) of seven each and fed low-protein high-/low-energy and
      high-protein high-/low-energy diets ad lib. Average daily gain (g; P < 0.05) and
      feed efficiency (P < 0.01) were significantly higher in lambs fed high energy
      than those with low-energy diets, and cost per kg gain ($) was significantly
      lower (P < 0.05) in low protein than high-protein diets. Dry matter intake (DMI)
      (g/day) was not significantly affected either by protein or energy level in the
      diet, but dry matter (DM), organic matter (OM), protein, and neutral detergent
      fiber (NDF) digestibilities were higher significantly (P < 0.01) in high
      protein/energy diets than low protein/energy diets. Crude protein (CP) intake
      (g/day) was significantly (P < 0.001) higher in lambs fed high protein than low
      protein diets. However, N balance (g/day) was significantly (P < 0.001) higher in
      lambs fed low protein than high-protein diets. It is concluded that feeding of
      SSBLR-based diet with low protein (CP 12.9 %) and high energy (9.4 MJ
      metabolizable energy (ME)/kg DM) was recommended for better performance, nitrogen
      retention, and returns from growing Deccani ram lambs. 

PMID- 25757880
TI  - Utilization of maternal health services among adolescent women in Bangladesh: A
      scoping review of the literature.
AB  - OBJECTIVE: To understand the health-seeking behaviour of adolescent women in
      Bangladesh with respect to the use of maternal health services. METHODS:
      Literature review of seven electronic databases: PubMed, ISI Web of Knowledge,
      PsycINFO, Embase, CINAHL, POPLINE and Global Health. Studies published in English
      between 1990 and 2013 which describe Bangladeshi adolescent women's healthcare
      seeking behaviour during pregnancy, delivery and post-partum were included.
      RESULTS: Twelve studies were included in this review. 11 used quantitative
      methods and one used a mixed-methods approach. All studies included married
      adolescent women only. Women with lower educational levels are less likely to
      seek skilled maternal health services than those with higher levels of education.
      Use of maternal health services is also less common among rural married
      adolescent women than women in urban areas. Being part of the richest bands of
      wealth, having had previous experiences of childbirth and higher women's autonomy
      positively influence the use of skilled maternal health services among married
      adolescent women in Bangladesh. Antenatal care is a key predictor of the use of
      skilled birth attendants for delivery and post-natal care. CONCLUSION: Maternal
      health-related programmes should be designed targeting rural and uneducated
      married adolescent women in Bangladesh. More qualitative investigations are
      required to broaden our understanding on maternal health-seeking behaviour of
      both married and unmarried adolescent women.

PMID- 25757881
TI  - Pattern transformation of heat-shrinkable polymer by three-dimensional (3D)
      printing technique.
AB  - A significant challenge in conventional heat-shrinkable polymers is to produce
      controllable microstructures. Here we report that the polymer material fabricated
      by three-dimensional (3D) printing technique has a heat-shrinkable property,
      whose initial microstructure can undergo a spontaneous pattern transformation
      under heating. The underlying mechanism is revealed by evaluating internal strain
      of the printed polymer from its fabricating process. It is shown that a uniform
      internal strain is stored in the polymer during the printing process and can be
      released when heated above its glass transition temperature. Furthermore, the
      internal strain can be used to trigger the pattern transformation of the heat
      shrinkable polymer in a controllable way. Our work provides insightful ideas to
      understand a novel mechanism on the heat-shrinkable effect of printed material,
      but also to present a simple approach to fabricate heat-shrinkable polymer with a
      controllable thermo-structural response. 

PMID- 25757882
TI  - Skeletal muscle size is a major predictor of intramuscular fat content regardless
      of age.
AB  - PURPOSE: Skeletal muscles of older individuals have a larger amount of
      intramuscular adipose tissue (IntraMAT) than those of younger individuals. It is
      not understood how aging affects the IntraMAT content of individual muscles of
      the thigh. We assessed the relationship between IntraMAT content and skeletal
      muscle cross-sectional area (CSA), subcutaneous adipose tissue CSA, biochemical
      blood profiles, and physical activity. METHODS: Fifteen older (70.7 +/- 3.8
      years) and 15 younger (20.9 +/- 0.3 years) men and women participated in this
      study. Magnetic resonance imaging of the right thigh was taken to measure
      IntraMAT content and skeletal muscle CSA for the quadriceps femoris (QF),
      hamstrings (HM), adductor (AD) muscle groups and subcutaneous adipose tissue CSA
      of the thigh. Fasting blood samples were collected to measure plasma lipids,
      adiponectin, and HbA1c levels. RESULTS: IntraMAT content in QF, HM, and AD for
      the Older group was significantly higher than in the Younger group. However,
      skeletal muscle CSA normalized by body weight (skeletal muscle CSA/bw) in the QF
      (P < 0.001) and total thigh (P < 0.01) were significantly lower in the Older
      group compared with the Younger group.There were no significant differences in HM
      and AD. Stepwise regression analysis with IntraMAT content as a dependent
      variable revealed that skeletal muscle CSA/bw of the thigh was the only
      predictive variable for IntraMAT content in Older and Younger groups. CONCLUSION:
      These results suggest that skeletal muscle size could be a major determinant of
      IntraMAT content regardless of age.

PMID- 25757883
TI  - Structural, nanomechanical, and computational characterization of D,L-cyclic
      peptide assemblies.
AB  - The rigid geometry and tunable chemistry of D,L-cyclic peptides makes them an
      intriguing building-block for the rational design of nano- and microscale
      hierarchically structured materials. Herein, we utilize a combination of electron
      microscopy, nanomechanical characterization including depth sensing-based bending
      experiments, and molecular modeling methods to obtain the structural and
      mechanical characteristics of cyclo-[(Gln-D-Leu)4] (QL4) assemblies. QL4 monomers
      assemble to form large, rod-like structures with diameters up to 2 MUm and
      lengths of tens to hundreds of micrometers. Image analysis suggests that large
      assemblies are hierarchically organized from individual tubes that undergo
      bundling to form larger structures. With an elastic modulus of 11.3 +/- 3.3 GPa,
      hardness of 387 +/- 136 MPa and strength (bending) of 98 +/- 19 MPa the peptide
      crystals are among the most robust known proteinaceous micro- and nanofibers. The
      measured bending modulus of micron-scale fibrils (10.5 +/- 0.9 GPa) is in the
      same range as the Young's modulus measured by nanoindentation indicating that the
      robust nanoscale network from which the assembly derives its properties is
      preserved at larger length-scales. Materials selection charts are used to
      demonstrate the particularly robust properties of QL4 including its specific
      flexural modulus in which it outperforms a number of biological proteinaceous and
      nonproteinaceous materials including collagen and enamel. The facile synthesis,
      high modulus, and low density of QL4 fibers indicate that they may find utility
      as a filler material in a variety of high efficiency, biocompatible composite
      materials.

PMID- 25757884
TI  - Proteomics for the detection of indirect markers of steroids treatment in bovine
      muscle.
AB  - Despite the ban by the European Union, anabolic steroids might still be illicitly
      employed in bovine meat production. The surveillance of misuse of such
      potentially harmful molecules is necessary to guarantee consumers' health.
      Analytical methods for drug residue control are based on LC-MS/MS, but their
      efficacy can be hindered due to undetectable residual concentrations as a result
      of low-dosage treatments. Screening methods based on the recognition of indirect
      biological effects of growth promoters' administration, such as the alteration of
      protein expression, can improve the efficacy of surveillance. The present study
      was aimed at identifying modifications in the muscle protein expression pattern
      between bulls treated with an ear implant (Revalor-XS(r)) containing trenbolone
      acetate (200 mg) and estradiol (40 mg), and untreated animals. The analysis of
      skeletal muscle was carried out using a tandem mass tags shotgun proteomics
      approach. We defined 28 candidate protein markers with a significantly altered
      expression induced by steroids administration. A subset of 18 candidate markers
      was validated by SRM and allowed to build a predictive model based on partial
      least square discriminant analysis. Our findings confirm the effectiveness of the
      proteomics approach as potential tool to overcome analytical limitations of drug
      residue monitoring. 

PMID- 25757885
TI  - Quantifying annual internal effective 137Cesium dose utilizing direct body-burden
      measurement and ecological dose modeling.
AB  - The Chernobyl Nuclear Power Plant (CNPP) accident represents one of the most
      significant civilian releases of 137Cesium (137Cs, radiocesium) in human history.
      In the Chernobyl-affected region, radiocesium is considered to be the greatest on
      going environmental hazard to human health by radiobiologists and public health
      scientists. The goal of this study was to characterize dosimetric patterns and
      predictive factors for whole-body count (WBC)-derived radiocesium internal dose
      estimations in a CNPP-affected children's cohort, and cross-validate these
      estimations with a soil-based ecological dose estimation model. WBC data were
      used to estimate the internal effective dose using the International Commission
      on Radiological Protection (ICRP) 67 dose conversion coefficient for 137Cs and
      MONDAL Version 3.01 software. Geometric mean dose estimates from each model were
      compared utilizing paired t-tests and intra-class correlation coefficients.
      Additionally, we developed predictive models for WBC-derived dose estimation in
      order to determine the appropriateness of EMARC to estimate dose for this
      population. The two WBC-derived dose predictive models identified 137Cs soil
      concentration (P<0.0001) as the strongest predictor of annual internal effective
      dose from radiocesium validating the use of the soil-based EMARC model. The
      geometric mean internal effective dose estimate of the EMARC model (0.183 mSv/y)
      was the highest followed by the ICRP 67 dose estimates (0.165 mSv/y) and the
      MONDAL model estimates (0.149 mSv/y). All three models yielded significantly
      different geometric mean dose (P<0.05) estimates for this cohort when stratified
      by sex, age at time of exam and season of exam, except for the mean MONDAL and
      EMARC estimates for 15- and 16-year olds and mean ICRP and MONDAL estimates for
      children examined in Winter. Further prospective and retrospective radio
      epidemiological studies utilizing refined WBC measurements and ecological model
      dose estimations, in conjunction with findings from animal toxicological studies,
      should help elucidate possible deterministic radiogenic health effects associated
      with chronic low-dose internal exposure to 137Cs.

PMID- 25757887
TI  - N-Cadherin, ADAM-10 and Aquaporin 1 expression in lung tissue exposed to fluoro
      edenite fibers: an immunohistochemical study.
AB  - Fluoro-edenite (FE) fibers are similar to other amphibole asbestos fibers. The
      scientific relevance of FE is due to its ability to lead to chronic inflammation
      and carcinogenesis in lung tissue shown after its inhalation. These fibers
      stimulate aberrant host cell proliferation and induce the release of cytokines,
      growth factors, reactive oxygen and nitrite species, which results in DNA damage.
      In previous studies, we showed that FE induces functional modifications in sheep
      and human lung fibroblasts and alveolar epithelial cells, where the
      overexpression of several molecules probably involved in pathological cellular
      mechanisms induced by FE exposition have been detected. However, the mechanisms
      of cellular and molecular toxicity and the cellular response to FE fibers are
      still not well known. N-cadherin, ADAM-10 and AQP1 are molecules involved in
      carcinogenesis and in inflammatory process. In this study we analyzed, through
      immunohistochemistry, their expression in the lung tissue of sheep exposed to FE.
      Our results showed different patterns of immunolabeling for N-cadherin, ADAM-10
      and AQP1. N-cadherin and ADAM-10 were more expressed in FE exposed lung tissue,
      when compared with the control. On the contrary, AQP1 was more expressed in non
      exposed lung tissue. These results suggest that N-Cadherin, ADAM-10 and AQP1 are
      probably involved in different pathological processes induced by FE fiber
      exposition. The aim of the study was to better understand the mechanisms of
      cellular and molecular toxicity and of cellular response to FE fibers in order to
      identify, in the future, a possible therapeutic intervention in cases of FE
      associated pathogenesis. 

PMID- 25757886
TI  - Human skin permeation of emerging mycotoxins (beauvericin and enniatins).
AB  - Currently, dermal exposure data of cyclic depsipeptide mycotoxins are completely
      absent. There is a lack of understanding about the local skin and systemic
      kinetics and effects, despite their widespread skin contact and intrinsic hazard.
      Therefore, we provide a quantitative characterisation of their dermal kinetics.
      The emerging mycotoxins enniatins (ENNs) and beauvericin (BEA) were used as model
      compounds and their transdermal kinetics were quantitatively evaluated, using
      intact and damaged human skin in an in vitro Franz diffusion cell set-up and
      ultra high-performance liquid chromatography (UHPLC)-MS analytics. We
      demonstrated that all investigated mycotoxins are able to penetrate through the
      skin. ENN B showed the highest permeation (kp,v=9.44 * 10(-6) cm/h), whereas BEA
      showed the lowest (kp,v=2.35 * 10(-6) cm/h) and the other ENNs ranging in
      between. Combining these values with experimentally determined solubility data,
      Jmax values ranging from 0.02 to 0.35 MUg/(cm(2) h) for intact skin and from 0.07
      to 1.11 MUg/(cm(2) h) for damaged skin were obtained. These were used to
      determine the daily dermal exposure (DDE) in a worst-case scenario. On the other
      hand, DDE's for a typical occupational scenario were calculated based on real
      life mycotoxin concentrations for the industrial exposure of food-related
      workers. In the latter case, for contact with intact human skin, DDE's up to
      0.0870 ng/(kg BW * day) for ENN A were calculated, whereas for impaired skin
      barrier this can even rise up to 0.3209 ng/(kg BW * day) for ENN B1. This
      knowledge is needed for the risk assessment after skin exposure of contaminated
      food, feed, indoor surfaces and airborne particles with mycotoxins. 

PMID- 25757888
TI  - Next generation sequencing analysis reveals that the ribonucleases RNase II,
      RNase R and PNPase affect bacterial motility and biofilm formation in E. coli.
AB  - BACKGROUND: The RNA steady-state levels in the cell are a balance between
      synthesis and degradation rates. Although transcription is important, RNA
      processing and turnover are also key factors in the regulation of gene
      expression. In Escherichia coli there are three main exoribonucleases (RNase II,
      RNase R and PNPase) involved in RNA degradation. Although there are many studies
      about these exoribonucleases not much is known about their global effect in the
      transcriptome. RESULTS: In order to study the effects of the exoribonucleases on
      the transcriptome, we sequenced the total RNA (RNA-Seq) from wild-type cells and
      from mutants for each of the exoribonucleases (?rnb, ?rnr and ?pnp). We compared
      each of the mutant transcriptome with the wild-type to determine the global
      effects of the deletion of each exoribonucleases in exponential phase. We
      determined that the deletion of RNase II significantly affected 187 transcripts,
      while deletion of RNase R affects 202 transcripts and deletion of PNPase affected
      226 transcripts. Surprisingly, many of the transcripts are actually down
      regulated in the exoribonuclease mutants when compared to the wild-type control.
      The results obtained from the transcriptomic analysis pointed to the fact that
      these enzymes were changing the expression of genes related with flagellum
      assembly, motility and biofilm formation. The three exoribonucleases affected
      some stable RNAs, but PNPase was the main exoribonuclease affecting this class of
      RNAs. We confirmed by qPCR some fold-change values obtained from the RNA-Seq
      data, we also observed that all the exoribonuclease mutants were significantly
      less motile than the wild-type cells. Additionally, RNase II and RNase R mutants
      were shown to produce more biofilm than the wild-type control while the PNPase
      mutant did not form biofilms. CONCLUSIONS: In this work we demonstrate how deep
      sequencing can be used to discover new and relevant functions of the
      exoribonucleases. We were able to obtain valuable information about the
      transcripts affected by each of the exoribonucleases and compare the roles of the
      three enzymes. Our results show that the three exoribonucleases affect cell
      motility and biofilm formation that are two very important factors for cell
      survival, especially for pathogenic cells.

PMID- 25757889
TI  - Metabolic flux analysis of Saccharomyces cerevisiae in a sealed winemaking
      fermentation system.
AB  - A sealed fermentation (SF) system and an anaerobic fermentation (AF) system
      (under normal atmospheric pressure conditions) were employed to study the
      influence of endogenous carbon dioxide (CO2) on the metabolism of Saccharomyces
      cerevisiae. The results showed that the fermentation stopped when 82.0 g L(-1)
      glucose was consumed and the endogenously produced CO2: pressure reached to 14.3
      MPa in SF system, while the sugar was used up during AF. The total yeast viable
      count in the end of AF was higher than that of SF. It was also observed that the
      ethanol yield in AF and SF was similar, the glycerol yield in AF was 1.26 times
      higher than that in SF, while the succinic acid and acetic acid yields in SF were
      24.7 and 26 times higher than that in AF, respectively. Additionally, this work
      provides a stoichiometric model used for metabolic flux analysis of S. cerevisiae
      to compare the flux distribution in SF and AF. The results showed that CO2 had an
      important effect on the pathways of oxaloacetic acid formation from pyruvic acid
      and ribose-5-phosphate formation from glucose-6-phosphate. However, the pathway
      of ethanol formation from pyruvic acid (decarboxylation reaction), catalyzed by
      pyruvate decarboxylase, was insensitive to CO2. 

PMID- 25757890
TI  - Catalytic properties of Phr family members of cell wall glucan remodeling
      enzymes: implications for the adaptation of Candida albicans to ambient pH.
AB  - Fungal wall formation is a dynamic process involving several categories of
      enzymes. The GH72 family of beta(1,3)-glucanosyltransferases is essential for the
      determination of cell shape, for cell integrity and for virulence in pathogenic
      fungi. Candida albicans has five GH72 genes: PHR1 and PHR2 are pH dependent, the
      first being expressed at pH >= 6 and repressed at lower pH and the second
      regulated in the opposite manner, PGA4 is transcribed independently of pH whereas
      PHR3 and PGA5 have low expression levels. To characterize the catalytic
      properties of Phr1p-2p and probe the activity of Pga4p, we heterologously
      expressed these proteins and used a fluorescent assay based on the transfer of
      oligosaccharyl units from a donor to a sulforhodamine-labeled acceptor. Phr1p-2p
      used exclusively beta-1,3-glucan or cell wall glucan as donor and laminarin
      derived oligosaccharides as acceptor. The acceptor efficiency increased with the
      length of the oligosaccharide. The temperature optimum was 30 degrees C. The pH
      optimum was 5.8 for Phr1p and 3 for Phr2p. Overall, adaptation to pH of C.
      albicans appears to involve a fine interplay among the pH-dependent activity of
      Phr1p and Phr2p, the pH-regulated expression of their genes and protein
      stability. Unexpectedly, Pga4p was inactive suggesting that it turned into a
      structural mannoprotein.

PMID- 25757891
TI  - Movement dynamics reflect a functional role for weak coupling and role structure
      in dyadic problem solving.
AB  - Successful interaction requires complex coordination of body movements. Previous
      research has suggested a functional role for coordination and especially
      synchronization (i.e., time-locked movement across individuals) in different
      types of human interaction contexts. Although such coordination has been shown to
      be nearly ubiquitous in human interaction, less is known about its function. One
      proposal is that synchrony supports and facilitates communication (Topics Cogn
      Sci 1:305-319, 2009). However, questions still remain about what the properties
      of coordination for optimizing communication might look like. In the present
      study, dyads worked together to construct towers from uncooked spaghetti and
      marshmallows. Using cross-recurrence quantification analysis, we found that dyads
      with loosely coupled gross body movements performed better, supporting recent
      work suggesting that simple synchrony may not be the key to effective performance
      (Riley et al. 2011). We also found evidence that leader-follower dynamics-when
      sensitive to the specific role structure of the interaction-impact task
      performance. We discuss our results with respect to the functional role of
      coordination in human interaction. 

PMID- 25757892
TI  - Dairy proteins in nutrition and food science: functional ingredients in the
      current global marketplace.

PMID- 25757893
TI  - Global market for dairy proteins.
AB  - This review examines the global market for dairy ingredients by assessing the
      global demand for dairy products in relation to major dairy ingredient
      categories. Each broad category of dairy ingredients is reviewed including its
      definition, production and trade status, key applications, and future trends.
      Ingredient categories examined include whole and skim milk powders (WMPs, SMPs),
      whey protein concentrates (WPCs) and whey protein isolates (WPIs), milk protein
      concentrates (MPCs) and milk protein isolates (MPIs), caseins, and caseinates.
      Increases in world population and improvements in socioeconomic conditions will
      continue to drive the demand for dairy products and ingredients in the future.
      Dairy proteins are increasingly recognized to have nutritional and functional
      advantages compared to many protein sources, and the variety of ingredients with
      different protein concentrations, functionality, and flavor can meet the needs of
      the increasingly global dairy consumption. A thorough understanding of the
      variety of ingredients, how the ingredients are derived from milk, and how the
      demand from particular markets affects the supply situation are critical elements
      in understanding the current ingredient marketplace. 

PMID- 25757894
TI  - Metabolic advantages of higher protein diets and benefits of dairy foods on
      weight management, glycemic regulation, and bone.
AB  - The Inst. of Medicine and World Health Organization have determined that 0.8 to
      0.83 g protein.kg(-1) .d(-1) is the quantity of protein required to establish
      nitrogen balance in nearly all healthy individuals. However, consuming higher
      protein diets may be metabolically advantageous, particularly for overweight and
      obese adults attempting weight loss, and for physically active individuals such
      as athletes and military personnel. Studies have demonstrated that higher protein
      diets may spare lean body mass during weight loss, promote weight management,
      enhance glycemic regulation, and increase intestinal calcium absorption, which
      may result in long-term improvements in bone health. The extent to which higher
      protein diets are beneficial is largely attributed to the digestive and
      absorptive properties, and also to the essential amino acid (EAA) content of the
      protein. Proteins that are rapidly digested and absorbed likely contribute to the
      metabolic advantages conferred by consuming higher protein diets. The EAA
      profiles, as well as the digestive and absorptive properties of dairy proteins,
      such as whey protein and casein, are particularly advantageous because they
      facilitate a rapid, robust, and sustained delivery of EAAs to the periphery. This
      article reviews the scientific literature assessing metabolic advantages
      associated with higher protein diets on weight management, glycemic regulation,
      and bone, with emphasis given to studies evaluating the potential benefits
      associated with dairy. 

PMID- 25757895
TI  - Innovative uses of milk protein concentrates in product development.
AB  - Milk protein concentrates (MPCs) are complete dairy proteins (containing both
      caseins and whey proteins) that are available in protein concentrations ranging
      from 42% to 85%. As the protein content of MPCs increases, the lactose levels
      decrease. MPCs are produced by ultrafiltration or by blending different dairy
      ingredients. Although ultrafiltration is the preferred method for producing MPCs,
      they also can be produced by precipitating the proteins out of milk or by dry
      blending the milk proteins with other milk components. MPCs are used for their
      nutritional and functional properties. For example, MPC is high in protein
      content and averages approximately 365 kcal/100 g. Higher-protein MPCs provide
      protein enhancement and a clean dairy flavor without adding significant amounts
      of lactose to food and beverage formulations. MPCs also contribute valuable
      minerals, such as calcium, magnesium, and phosphorus, to formulations, which may
      reduce the need for additional sources of these minerals. MPCs are
      multifunctional ingredients and provide benefits, such as water binding, gelling,
      foaming, emulsification, and heat stability. This article will review the
      development of MPCs and milk protein isolates including their composition,
      production, development, functional benefits, and ongoing research. The
      nutritional and functional attributes of MPCs are discussed in some detail in
      relation to their application as ingredients in major food categories. 

PMID- 25757896
TI  - Supplemental protein in support of muscle mass and health: advantage whey.
AB  - Skeletal muscle is an integral body tissue playing key roles in strength,
      performance, physical function, and metabolic regulation. It is essential for
      athletes to ensure that they have optimal amounts of muscle mass to ensure peak
      performance in their given sport. However, the role of maintaining muscle mass
      during weight loss and as we age is an emerging concept, having implications in
      chronic disease prevention, functional capacity, and quality of life. Higher
      protein diets have been shown to: (1) promote gains in muscle mass, especially
      when paired with resistance training; (2) spare muscle mass loss during caloric
      restriction; and (3) attenuate the natural loss of muscle mass that accompanies
      aging. Protein quality is important to the gain and maintenance of muscle mass.
      Protein quality is a function of protein digestibility, amino acid content, and
      the resulting amino acid availability to support metabolic function. Whey protein
      is one of the highest-quality proteins given its amino acid content (high
      essential, branched-chain, and leucine amino acid content) and rapid
      digestibility. Consumption of whey protein has a robust ability to stimulate
      muscle protein synthesis. In fact, whey protein has been found to stimulate
      muscle protein synthesis to a greater degree than other proteins such as casein
      and soy. This review examines the existing data supporting the role for protein
      consumption, with an emphasis on whey protein, in the regulation of muscle mass
      and body composition in response to resistance training, caloric restriction, and
      aging. 

PMID- 25757898
TI  - Continuous levodopa infusion is better-for now.

PMID- 25757899
TI  - Nursing best practices to prevent stroke in women.

PMID- 25757900
TI  - PHASES Score for Prediction of Intracranial Aneurysm Growth.
AB  - BACKGROUND AND PURPOSE: Growth of an intracranial aneurysm occurs in around 10%
      of patients at 2-year follow-up imaging and may be associated with aneurysm
      rupture. We investigated whether PHASES, a score providing absolute risks of
      aneurysm rupture based on 6 easily retrievable risk factors, also predicts
      aneurysm growth. METHODS: In a multicenter cohort of patients with unruptured
      intracranial aneurysms and follow-up imaging with computed tomography angiography
      or magnetic resonance angiography, we performed univariable and multivariable Cox
      regression analyses for the predictors of the PHASES score at baseline, with
      aneurysm growth as outcome. We calculated hazard ratios and corresponding 95%
      confidence intervals (CI), with the PHASES score as continuous variable and after
      division into quartiles. RESULTS: We included 557 patients with 734 unruptured
      aneurysms. Eighty-nine (12%) aneurysms in 87 patients showed growth during a
      median follow-up of 2.7 patient-years (range 0.5-10.8). Per point increase in
      PHASES score, hazard ratio for aneurysm growth was 1.32 (95% CI, 1.22-1.43). With
      the lowest quartile of the PHASES score (0-1) as reference, hazard ratios were
      for the second (PHASES 2-3) 1.07 (95% CI, 0.49-2.32), the third (PHASES 4) 2.29
      (95% CI, 1.05-4.95), and the fourth quartile (PHASES 5-14) 2.85 (95% CI, 1.43
      5.67). CONCLUSIONS: Higher PHASES scores were associated with an increased risk
      of aneurysm growth. Because higher PHASES scores also predict aneurysm rupture,
      our findings suggest that aneurysm growth can be used as surrogate outcome
      measure of aneurysm rupture in follow-up studies on risk prediction or
      interventions aimed to reduce the risk of rupture.

PMID- 25757901
TI  - Letter by Hartung and Cottrell regarding article, "What is the use of hypothermia
      for neuroprotection after out-of-hospital cardiac arrest?".

PMID- 25757902
TI  - The effects of chronic radiation of gamma ray on protein expression and oxidative
      stress in Brachypodium distachyon.
AB  - PURPOSE: To compare the effects of gamma-irradiation on biochemical responses and
      growth, six-week-old Brachypodium plants were chronically exposed to gamma
      irradiation for 30 days at various dosages. MATERIALS AND METHODS: Growth surveys
      of Brachypodium plants in response to different dosages of gamma-irradiation were
      conducted to compare physiological changes between irradiated and non-irradiated
      plants. Photosynthetic pigments, soluble sugar content, activities of antioxidant
      enzymes, and malonaldehyde (MDA) induced by reactive oxygen species (ROS)
      production were also measured. RESULTS: Gamma-irradiation had a negative
      influence on the average plant height, leaf length, leaf width, and fresh weight.
      Photosynthetic pigment levels decreased with increasing dosages of gamma
      irradiation, while soluble sugar content slightly increased. Gamma-irradiation
      responsive proteins were detected and identified by two-dimensional gel
      electrophoresis (2D-PAGE) and matrix-assisted laser desorption ionization time-of
      flight (MALDI-TOF). The proteins had a role in photosynthetic carbon fixation,
      anabolic pathway glycolysis, mitochondrial ATP production, and oxidative stress
      response regulation. MDA levels and activities of antioxidant enzymes such as
      superoxide dismutase (SOD), ascorbate peroxidase (APX), catalase (CAT), and
      peroxidase (POD) increased with the increase in gamma-irradiation dosage level.
      CONCLUSIONS: This study provides some basic information regarding responses to
      gamma-irradiation, and provides valuable physiological and biological data on the
      effects of different gamma-irradiation dosages on Triticeae species.

PMID- 25757903
TI  - Fe(NO3)3-assisted large-scale synthesis of Si3N4 nanobelts from quartz and
      graphite by carbothermal reduction-nitridation and their photoluminescence
      properties.
AB  - The large-scale synthesis of Si3N4 nanobelts from quartz and graphite on a
      graphite-felt substrate was successfully achieved by catalyst-assisted
      carbothermal reduction-nitridation. The phase composition, morphology, and
      microstructure of Si3N4 nanobelts were investigated by X-ray diffraction, Fourier
      transform infrared spectroscopy, field-emission scanning electron microscopy,
      energy-dispersive spectroscopy, transmission electron microscopy, and high
      resolution transmission electron microscopy. The Si3N4 nanobelts were ~4-5 mm
      long and ~60 nm thick and exhibited smooth surfaces and flexible shapes. The
      Si3N4 nanobelts were well crystallized and grow along the [101] direction. The
      growth is dominated by the combined mechanisms of vapor-liquid-solid base growth
      and vapor-solid tip growth. The Fe(NO3)3 played a crucial role in promoting the
      nanobelt formation in the initial stage. The room-temperature photoluminescence
      spectrum of Si3N4 nanobelts consists of three emission peaks centered at 413,
      437, and 462 nm, indicating potential applications in optoelectronic nanodevices.

PMID- 25757904
TI  - The impact of physician posture during oncology patient encounters.
AB  - Non-verbal communication is an important component of the physician-patient
      interaction. Oncology patients face specific emotional and psychological issues
      requiring additional physician emotional support. Multiple studies in oncology
      patients have revealed that patients perceive physicians seated during the
      medical interview to be more compassionate, caring, and likely to spend more time
      with the patients. These are all associated with improved patient outcomes.
      Barriers to sitting may be due to those imposed by time, space, and reduced
      perceived benefit of sitting by the physician. Although a sitting posture alone
      is unlikely to compensate for poor communication skills, assessing patient
      preference to physician posture, and following their preference, can be a simple
      way of improving communication, and thus patient outcomes, especially in oncology
      patients. The widespread introduction of the electronic medical record (EMR)
      system over the last decade has added a "third wheel" to the original dyadic
      physician-patient relationship. Physician posture and eye gaze towards to the EMR
      and its components has a deleterious effect on communication. Appropriate
      training and sensitization in this regard should be provided for physicians. 

PMID- 25757906
TI  - Expression of seipin in adipose tissue rescues lipodystrophy, hepatic steatosis
      and insulin resistance in seipin null mice.
AB  - OBJECTIVES: Gene mutations in an ER protein seipin result in congenital
      generalized lipodystrophy (CGL) in humans, accompanied with hepatic steatosis and
      insulin resistance. Seipin gene is highly expressed in the brain, testis and
      adipose tissue. Seipin globally deficient mice (SKO) displayed similar phenotypes
      as human counterparts. It has been demonstrated that adipose-specific seipin
      knockout mice at elder age were indistinguishable from SKO mice. Due to the large
      mass of adipose tissue in the body, we hypothesized that seipin in adipose tissue
      might be responsible for the multiple metabolism-related abnormalities in SKO
      mice. METHODS AND RESULTS: Transgenic mice with adipose-specific expression of
      human seipin gene driven by aP2 promoter were generated and crossed with SKO mice
      to obtain adipose-specific seipin reconstitute (Seipin-RE) mice. In comparison
      with wild-type (WT) and SKO mice, the Seipin-RE mice exhibited normal plasma
      triglyceride and non-esterified fatty acids upon fasting, recovered adipose
      tissue mass, restored epididymal and subcutaneous fat pads morphology and
      partially recovered plasma leptin and adiponectin levels. Moreover, hepatic
      steatosis and insulin resistance was also absent in these mice. CONCLUSION: Our
      study demonstrates that expression of seipin in adipose tissue alone could rescue
      dyslipidemia, lipodystrophy, hepatic steatosis and insulin resistance in SKO
      mice.

PMID- 25757905
TI  - Transmissibility of tuberculosis among school contacts: an outbreak investigation
      in a boarding middle school, China.
AB  - Tuberculosis (TB) outbreak occurred in a boarding middle school of China. We
      explored its probable sources and quantified the transmissibility and
      pathogenicity of TB. Clinical evaluation, tuberculin skin testing and chest
      radiography were conducted to identify TB cases. Mycobacterium tuberculosis
      isolates underwent genotyping analysis to identify the outbreak source. A chain
      binomial transmission model was used to evaluate transmissibility and
      pathogenicity of TB. A total of 46 active cases were ascertained among 258
      students and 15 teachers/staff, an attack rate of 16.8%. Genetic analyses
      revealed two groups of M. tuberculosis cocirculating during the outbreak and
      possible importation from local communities. Secondary attack rates among
      students were 4.1% (2.9%, 5.3%) within grade and 7.9% (4.9%, 11%) within class.
      An active TB case was estimated to infect 8.4 (7.2, 9.6) susceptible people on
      average. The smear-positive cases were 28 (8, 101) times as infective as smear
      negative cases. Previous BCG vaccination could reduce the probability of
      developing symptoms after infection by 70% (1.4%, 91%). The integration of
      clinical evaluation, genetic sequencing, and statistical modeling greatly
      enhanced our understanding of TB transmission dynamics. Timely diagnosis of smear
      positive cases, especially in the early phase of the outbreak, is the key to
      preventing further spread among close contacts.

PMID- 25757907
TI  - Inhibitory effect of exendin-4 on secretory group IIA phospholipase A2.
AB  - Exendin-4 (EX4), a glucagon-like peptide-1 receptor agonist, has been reported to
      attenuate myocardial ischemia and reperfusion injury and inflammatory or
      oxidative responses. The expression level of secretory group IIA phospholipase A2
      (sPLA2-IIA) is elevated in inflammatory diseases. Lipopolysaccharide (LPS)
      upregulates the expression of sPLA2-IIA in human umbilical vein endothelial cells
      (HUVECs). Here, EX4 was examined for its effects on the expression and activity
      of sPLA2-IIA in HUVECs and mice. Pre-treatment of cells or mice with EX4
      inhibited LPS-induced sPLA2-IIA expression and activity. Additionally, EX4
      suppressed LPS-induced activation of cytosolic phospholipase A2 (cPLA2) and
      extracellular signal-regulated kinase (ERK) 1/2. Therefore, these results show
      that EX4 inhibited LPS-induced expression of sPLA2-IIA by suppressing cPLA2 and
      ERK 1/2. 

PMID- 25757908
TI  - Benzidine induces epithelial-mesenchymal transition in human uroepithelial cells
      through ERK1/2 pathway.
AB  - Prolonged benzidine exposure is a known cause of urothelial carcinoma (UC).
      Benzidine-induced epithelial-to-mesenchymal transition (EMT) is critically
      involved in cell malignant transformation. The role of ERK1/2 in regulating
      benzidine-triggered EMT has not been investigated. This study was to investigate
      the regulatory role of ERK1/2 in benzidine-induced EMT. By using wound healing
      and transwell chamber migration assays, we found that benzidine could increase SV
      HUC-1 cells invasion activity, western blotting and Immunofluorescence showed
      that the expression levels of Snail, beta-catenin, Vimentin, and MMP-2 were
      significantly increased, while, the expression levels of E-cadherin, ZO-1 were
      decreased. To further demonstrate the mechanism in this process, we found that
      the phosphorylation of ERK1/2, p38, JNK and AP-1 proteins were significantly
      enhanced compared to the control group (*P < 0.05). Afterward, treated with MAPK
      pathways inhibitors, only ERK inhibitor(U0126)could reduce the expression of EMT
      markers in SV-HUC-1 cells, but not p38 and JNK inhibitor(SB203580, SP600125),
      which indicated that benzidine induces the epithelial-mesenchymal transition in
      human uroepithelial cells through ERK1/2 pathway. Taken together, findings from
      this study could provide into the molecular mechanisms by which benzidine exerts
      its bladder-cancer-promoting effect as well as its target intervention. 

PMID- 25757909
TI  - Protection of pancreatic beta-cells against glucotoxicity by short-term treatment
      with GLP-1.
AB  - Glucagon-like peptide-1 (GLP-1) reduces pancreatic beta-cell apoptosis in type 2
      diabetes. Glucotoxiciy is a main cause of beta-cell apoptosis in type 2 diabetes.
      The aims of this study were to investigate the anti-apoptotic mechanisms of GLP-1
      against glucotoxicity and whether physiological short-term treatment with GLP-1
      can protect beta-cells from glucotoxicity-induced apoptosis. GLP-1 treatment for
      only 30 min alleviated high glucose-induced beta-cell apoptosis. The effect of
      GLP-1 was related with phosphoinositide 3-kinase (PI3K)/AKT-S473 phosphorylation.
      The increase in pAKT-S473 led to suppression of FoxO-1. GLP-1-induced AKT-S473
      activation and FoxO-1 suppression were abolished by the selective inactivation of
      mTOR complex (mTORC) 2 using small interfering RNA directed towards the rapamycin
      insensitive companion of mTOR. The protective effect of GLP-1 on beta-cell
      apoptosis was also abolished by the selective inactivation of mTORC2. Hence, the
      protective effect of GLP-1 against glucotoxicity may be mediated by FoxO-1
      suppression through the PI3K/mTORC2/AKT-S473 phosphorylation. This report
      provides evidence that short-term treatment with GLP-1 is beneficial to protect
      against glucotoxicity-induced beta-cell apoptosis. 

PMID- 25757910
TI  - MicroRNA-26a overexpression protects RGC-5 cells against H2O2-induced apoptosis.
AB  - BACKGROUND: We intended to examine the functional role of microRNA 26 (miR-26a)
      in regulating H2O2-induced cytotoxicity and apoptosis in RGC-5 cells in vitro.
      METHOD: Various concentrations of H2O2 (0-1000 MUM) were added in RGC-5 culture.
      Cell cytotoxicity was monitored by viability assay and gene expression level of
      miR-26a examined by qRT-PCR. MicroRNA-26a mimic was then applied in the RGC-5
      culture to examine its effect on upregulating endogenous miR-26a and rescuing
      H2O2-induced cytotoxicity. TUNEL immunostaining assay was used to further assess
      the protective effect of upregulating miR-26a on H2O2-induced apoptosis in RGC-5
      cells. Direct targeting of miR-26a on Phosphatase and tensin homolog (PTEN)
      signaling pathway was assessed by luciferase assay and western blotting. PTEN was
      then ectopically over-expressed in RGC-5. And its effects on miR-26a mediated
      apoptosis protection in RGC-5 were investigated by western blot and TUNEL assay.
      RESULTS: H2O2 induced cytotoxicity and down-regulated miR-26a in dose-dependent
      manner in RGC-5 cells. MiR-26a-mimic upregulated endogenous miR-26a gene levels,
      and then reduced H2O2-induced cytotoxicity, as well as H2O2-induced apoptosis in
      RGC-5 cells. PTEN was directly targeted by miR-26a. PTEN protein was upregulated,
      and phosphorylated AKT protein down-regulated while miR-26a was upregulated to
      reduce H2O2-induced apoptosis. Finally, overexpressing PTEN reversed the
      protective effect of miR-26a upregulation on RGC-5 apoptosis. CONCLUSION:
      Upregulating miR-26a protects RGC-5 cell against cytotoxicity and apoptosis,
      probably through down-regulation of PTEN.

PMID- 25757911
TI  - Improving the osteointegration of Ti6Al4V by zeolite MFI coating.
AB  - Osteointegration is crucial for success in orthopedic implantation. In recent
      decades, there have been numerous studies aiming to modify titanium alloys, which
      are the most widely used materials in orthopedics. Zeolites are solid
      aluminosilicates whose application in the biomedical field has recently been
      explored. To this end, MFI zeolites have been developed as titanium alloy
      coatings and tested in vitro. Nevertheless, the effect of the MFI coating of
      biomaterials in vivo has not yet been addressed. The aim of the present work is
      to evaluate the effects of MFI-coated Ti6Al4V implants in vitro and in vivo.
      After surface modification, the surface was investigated using field emission
      scanning electron microscopy (FE-SEM) and energy dispersive spectroscopy (EDS).
      No difference was observed regarding the proliferation of MC3T3-E1 cells on the
      Ti6Al4V (Ti) and MFI-coated Ti6Al4V (M-Ti) (p > 0.05). However, the attachment of
      MC3T3-E1 cells was found to be better in the M-Ti group. Additionally, ALP
      staining and activity assays and quantitative real-time RT-PCR indicated that
      MC3T3-E1 cells grown on the M-Ti displayed high levels of osteogenic
      differentiation markers. Moreover, Van-Gieson staining of histological sections
      demonstrated that the MFI coating on Ti6Al4V scaffolds significantly enhanced
      osteointegration and promoted bone regeneration after implantation in rabbit
      femoral condylar defects at 4 and 12 weeks. Therefore, this study provides a
      method for modifying Ti6Al4V to achieve improved osteointegration and
      osteogenesis. 

PMID- 25757912
TI  - The important role of surface ligand on CdSe/CdS core/shell nanocrystals in
      affecting the efficiency of H2 photogeneration from water.
AB  - The use of colloidal semiconductor nanocrystals (NCs), especially those with a
      core/shell structure, for photocatalytic hydrogen (H2) production from water is
      currently one of the hottest research fields. Although the ligand on the
      semiconductor NC surface is crucial to the optical and optoelectronic properties
      of the NC, the study of the ligand effect on the photocatalytic activity of H2
      generation is rarely reported. Herein, we employ nearly monodispersed CdSe/CdS
      core/shell NCs as a model photocatalytic system, and three kinds of ligands with
      different numbers of functional thiol groups (i.e., poly(acrylic acid), 3
      mercaptopropionic acid and 2,3-dimercaptosuccinic acid) are selected as the
      ligands to investigate the effect of ligand on the efficiency of H2
      photogeneration. The results show that the H2 photogeneration efficiency is
      highly dependent on the surface ligand of the NCs, and it increases with the
      increase of the number of the functional thiol groups in the ligand, and
      correspondingly, the photoluminescence intensity and average fluorescence
      lifetime, which are measured by steady state and time-resolved fluorescence
      measurements, are decreased. The surface trap-related charge separation
      efficiency, which is mediated by surface coating with different ligands, is
      supposed to cause the distinct ligand-dependent performance in the H2 evolution.

PMID- 25757913
TI  - Relationship between hypothalamic-pituitary-adrenal axis dysregulation and
      insulin resistance in elderly patients with depression.
AB  - Cortisol dysregulation has been proposed to be involved in depression.
      Hypothalamic-pituitary-adrenal (HPA) axis dysregulation associated with major
      depressive disorder (MDD) was previously reported to be higher in the elderly.
      Furthermore, insulin resistance and the prevalence of type 2 diabetes are known
      to increase with aging. The aim of the present study was to determine whether a
      relationship existed between plasma cortisol levels following the
      dexamethasone/corticotrophin-releasing hormone (DEX/CRH) test and insulin
      resistance evaluated by the homeostasis model assessment of insulin resistance
      (HOMA-R) in elderly MDD subjects. Fifteen unmedicated MDD inpatients and 17 age-
      and sex-matched healthy controls participated in this study. After overnight
      fasting, blood samples were collected to measure plasma glucose and insulin
      concentrations, estimate HOMA-R, and perform the DEX/CRH test to evaluate HPA
      axis function. The value of the area under the time curve of plasma cortisol
      concentrations (CortAUC) and peak cortisol values (Cortpeak) following the
      administration of DEX/CRH both correlated with HOMA-R in MDD group. In contrast,
      neither CortAUC nor Cortpeak correlated with HOMA-R in controls. This is the
      first study to directly demonstrate the relationship between HPA axis
      dysregulation assessed with the DEX/CRH test and the index of insulin resistance
      estimated as HOMA-R in elderly MDD patients. 

PMID- 25757914
TI  - Ipsilateral hippocampal atrophy is associated with long-term memory dysfunction
      after ischemic stroke in young adults.
AB  - Memory impairment after stroke in young adults is poorly understood. In elderly
      stroke survivors memory impairments and the concomitant loss of hippocampal
      volume are usually explained by coexisting neurodegenerative disease (e.g.,
      amyloid pathology) in interaction with stroke. However, neurodegenerative
      disease, such as amyloid pathology, is generally absent at young age.
      Accumulating evidence suggests that infarction itself may cause secondary
      neurodegeneration in remote areas. Therefore, we investigated the relation
      between long-term memory performance and hippocampal volume in young patients
      with first-ever ischemic stroke. We studied all consecutive first-ever ischemic
      stroke patients, aged 18-50 years, admitted to our academic hospital center
      between 1980 and 2010. Episodic memory of 173 patients was assessed using the Rey
      Auditory Verbal Learning Test and the Rey Complex Figure and compared with 87
      stroke-free controls. Hippocampal volume was determined using FSL-FIRST, with
      manual correction. On average 10 years after stroke, patients had smaller
      ipsilateral hippocampal volumes compared with controls after left-hemispheric
      stroke (5.4%) and right-hemispheric stroke (7.7%), with most apparent memory
      dysfunctioning after left-hemispheric stroke. A larger hemispheric stroke was
      associated with a smaller ipsilateral hippocampal volume (b=-0.003, P<0.0001).
      Longer follow-up duration was associated with smaller ipsilateral hippocampal
      volume after left-hemispheric stroke (b=-0.028 ml, P=0.002) and right-hemispheric
      stroke (b=-0.015 ml, P=0.03). Our results suggest that infarction is associated
      with remote injury to the hippocampus, which may lower or expedite the threshold
      for cognitive impairment or even dementia later in life.

PMID- 25757915
TI  - Challenges in retinal circuit regeneration: linking neuronal connectivity to
      circuit function.
AB  - Tremendous progress has been made in retinal regeneration, as exemplified by
      successful transplantation of retinal pigment epithelia and photoreceptor cells
      in the adult retina, as well as by generation of retinal tissue from embryonic
      stem cells and induced pluripotent cells. However, it remains unknown how new
      photoreceptors integrate within retinal circuits and contribute to vision
      restoration. There is a large gap in our understanding, at both the cellular and
      behavioral levels, of the functional roles of new neurons in the adult retina.
      This gap largely arises from the lack of appropriate methods for analyzing the
      organization and function of new neurons at the circuit level. To bridge this gap
      and understand the functional roles of new neurons in living animals, it will be
      necessary to identify newly formed connections, correlate them with function,
      manipulate their activity, and assess the behavioral outcome of these
      manipulations. Recombinant viral vectors are powerful tools not only for
      controlling gene expression and reprogramming cells, but also for tracing cell
      fates and neuronal connectivity, monitoring biological functions, and
      manipulating the physiological state of a specific cell population. These virus
      based approaches, combined with electrophysiology and optical imaging, will
      provide circuit-level insight into neural regeneration and facilitate new
      strategies for achieving vision restoration in the adult retina. Herein, we
      discuss challenges and future directions in retinal regeneration research. 

PMID- 25757916
TI  - Flexibility of the coordination geometry at the N-site of Cu(II)2 human serum
      transferrin induced by the different orientations of Arg124.
AB  - The ESR spectra of dicupric human serum-transferrin (serum-Tf) were measured from
      -20 to 37 degrees C in the liquid state (56% glycerol at pH 7.6). Two
      coordination geometries (types B-1 and B-2) with different ESR parameters were
      present at the N-site. The contents of the coordination geometry of type B-1 at
      the N-site increased as the temperature increased. The equilibrium constant
      between the coordination geometries of types B-1 and B-2 was determined by ESR
      spectra. The enthalpy value from type B-2 to B-1 was +5.3 kcal/mol, as obtained
      from a van't Hoff plot. The two conformational energies of the cluster models of
      the copper-binding site at the N-site of dicupric human serum-Tf, where the
      Arg124 residue was oriented in two different directions (conformations I and II),
      were calculated by Density Functional Theory, and the enthalpy value from
      conformation II to I was +2.1 kcal/mol. The enthalpy value was similar to that
      (+5.3 kcal/mol) obtained by the coordination geometrical change from type B-2 to
      B-1 in Cu(II)2 serum-Tf. In conformations I and II, the residue of Arg124 at the
      N-site is located either far from or near the copper-binding site, respectively,
      and in both cases the coordination geometry of the cupric ions at the N-site has
      changed from a flattened tetrahedron to a trigonal bipyramid. This result implies
      that the ESR spectral change from type B-2 to B-1 is caused by the presence of
      two different orientations of Arg124 in the change from conformation II to I. 

PMID- 25757917
TI  - Improvement of transdermal delivery of sumatriptan succinate using a novel self
      dissolving microneedle array fabricated from sodium hyaluronate in rats.
AB  - The purpose of the present study was to develop an alternative transdermal
      formulation containing sumatriptan succinate (SS) for the treatment of migraine.
      Novel self-dissolving SS-loaded microneedle arrays (MNs) were fabricated from
      sodium hyaluronate and their efficacy for transdermal delivery of SS was
      characterized. The resulting MNs maintained their skin piercing abilities for at
      least 30 min after being placed at a high relative humidity of 75%. Rapid release
      of SS from the MNs was also observed in vitro. Optical coherence tomography
      images demonstrated that MNs were able to successfully pierce into rat skin
      without any bending or cracking, and needles were completely dissolved within 1
      h. MNs significantly increased transepidermal water loss; however, skin barrier
      function gradually recovered to control levels within 24 h, in contrast to the
      skin damage observed after tape stripping treatment. These findings indicated
      that the micropores created by MNs quickly resealed, and that the skin damage was
      reversible. Furthermore, a dose-dependent plasma concentration of SS was obtained
      after transdermal delivery using SS-loaded MNs in rats. Absorption of SS
      delivered by MNs was similar to that observed after subcutaneous injection and
      was associated with high bioavailability (ca. 90%), which was much higher than
      that produced by oral administration. These findings suggested that application
      of SS-loaded MNs to the skin provided an effective alternative approach to
      enhance the transdermal delivery of SS without serious skin damage, and would be
      likely to improve patient compliance. 

PMID- 25757918
TI  - Evaluation of antitumor effects of folate-conjugated methyl-beta-cyclodextrin in
      melanoma.
AB  - Melanoma is a life-threatening disorder and its incidence is increasing
      gradually. Despite the numerous treatment approaches, conventional systemic
      chemotherapy has not reduced the mortality rate among melanoma patients, probably
      due to the induction of toxicity to normal tissues. Recently, we have developed
      folate-conjugated methyl-beta-cyclodextrin (FA-M-beta-CyD) and clarified its
      potential as a new antitumor agent involved in autophagic cell death. However, it
      remains uncertain whether FA-M-beta-CyD exerts anticancer effects against
      melanomas. Therefore, in this study, we investigated the effects of FA-M-beta-CyD
      on the folate receptor-alpha (FR-alpha)-expressing melanoma cell-selective
      cytotoxic effect. FA-M-beta-CyD showed cytotoxic effects in Ihara cells, a human
      melanoma cell line expressing FR-alpha. In sharp contrast to methyl-beta
      cyclodextrin, FA-M-beta-CyD entered Ihara cells [FR-alpha(+)] through FR-alpha
      mediated endocytosis. Additionally, FA-M-beta-CyD elicited the formation of
      autophagosomes in Ihara cells. Notably, FA-M-beta-CyD suppressed melanoma growth
      in BALB/c nude recombinase-activating gene-2 (Rag-2)/Janus kinase 3 (Jak3) double
      deficient mice bearing Ihara cells. Therefore, these results suggest that FA-M
      beta-CyD could be utilized as a potent anticancer agent for melanoma chemotherapy
      by regulating autophagy. 

PMID- 25757919
TI  - Overcoming stability challenges in the quantification of tissue nucleotides:
      determination of 2'-C-methylguanosine triphosphate concentration in mouse liver.
AB  - A conventional, rapid and high throughput method for tissue extraction and
      accurate and selective LC-MS/MS quantification of 2'-C-methylguanosine
      triphosphate (2'-MeGTP) in mouse liver was developed and qualified.
      Trichloroacetic acid (TCA) was used as the tissue homogenization reagent that
      overcomes instability challenges of liver tissue nucleotide triphosphates due to
      instant ischemic degradation to mono- and diphosphate nucleotides. Degradation of
      2'-MeGTP was also minimized by harvesting livers using in situ clamp-freezing or
      snap-freezing techniques. The assay also included a sample clean-up procedure
      using weak anion exchange solid phase extraction followed by ion exchange
      chromatography and tandem mass spectrometry detection. The linear assay range was
      from 50 to 10000 pmol/mL concentration in liver homogenate (250-50000 pmol/g in
      liver tissue). The method was qualified over three intraday batches for accuracy,
      precision, selectivity and specificity. The assay was successfully applied to
      pharmacokinetic studies of 2'-MeGTP in liver tissue samples after single oral
      doses of IDX184, a nucleotide prodrug inhibitor of the viral polymerase for the
      treatment of hepatitis C, to mice. The study results suggested that the clamp
      freezing liver collection method was marginally more effective in preventing 2'
      MeGTP degradation during liver tissue collection compared to the snap-freezing
      method. 

PMID- 25757920
TI  - Nano-mechanical reinforcement in drug-resistant ovarian cancer cells.
AB  - The mechanical properties of cells are considered promising biomarkers for the
      early detection of cancer and the testing of drug efficacy against it.
      Nevertheless, generalized correlations between drug resistance and the nano
      mechanical properties of cancer cells are yet to be defined due to the lack of
      necessary studies. In this study, we conducted atomic force microscopy (AFM)
      based nano-mechanical measurements of cisplatin-sensitive (A2780) and cisplatin
      resistant (A2780cis) ovarian cancer cells. The difference in the efficacy of
      cisplatin between A2780 and A2780cis was confirmed in the 3-(4,5-dimethylthiazol
      2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) assay. We
      observed that the cisplatin-resistant ovarian cancer cells were more motile than
      cisplatin-sensitive cells based on the results of the wound closure experiment,
      and the AFM experiments showed that drug resistance induced nano-mechanical
      stiffening of the ovarian cancer cells. Increased mechanical stiffness caused by
      cisplatin resistance was consistent with the confocal microscopy images showing
      more distinct actin stress fibers in A2780cis than in A2780 cells. The down
      regulation of vinculin implicated the actin-driven elongation as a major motile
      mode for A2780cis cells. Our results consistently indicated that the acquisition
      of drug resistance in ovarian cancer cells induces an extensive reorganization of
      the actin cytoskeleton, which governs the cellular mechanical properties,
      motility, and possibly intracellular drug transportation. 

PMID- 25757921
TI  - Pharmacokinetic-pharmacodynamic analysis of sunitinib-induced thrombocytopenia in
      Japanese patients with renal cell carcinoma.
AB  - The aim of the present study was to clarify the therapeutic range and adequate
      dose of sunitinib in Japanese renal cell carcinoma patients by means of a
      pharmacokinetic-pharmacodynamic analysis of sunitinib-induced thrombocytopenia.
      Six patients with renal cell carcinoma were enrolled in this study. After
      starting the sunitinib treatment, between three and seven blood samples were
      obtained from each patient just before the administration of sunitinib. Serum
      concentrations of sunitinib and its active metabolite N-desethyl-sunitinib were
      fit to the 1-compartment model with first-order absorption. Changes in platelet
      counts were fit to the pharmacokinetic-pharmacodynamic model, in which the
      proliferation of platelet progenitor cells was assumed to be linearly inhibited
      by sunitinib and its metabolite. All patients using 50 mg as an initial dose of
      sunitinib developed grade 2 or 3 thrombocytopenia. The pharmacokinetic
      pharmacodynamic model created successfully described the time course of sunitinib
      induced thrombocytopenia and could predict changes in platelet counts after
      alterations to the dosage of sunitinib administered. The simulation results
      indicated that the total trough level of sunitinib to avoid severe
      thrombocytopenia should be <100 ng/mL, and also that the initial daily dose of
      sunitinib could be reduced to 37.5 mg or 25 mg in most Japanese patients. In
      addition to the pharmacokinetic-guided dosage adjustment, the careful monitoring
      of platelet counts is required for the safe use of sunitinib. 

PMID- 25757922
TI  - Comparative study of the anti-leukemic effects of imatinib mesylate, GlivecTM
      tablet and its generic formulation, OHK9511.
AB  - Long-term treatment with imatinib mesylate (IM) allows patients with chronic
      myeloid leukemia (CML) to live a near-normal lifespan. However, the fact that
      tyrosine kinase inhibitors, including IM, are extremely expensive is a major
      cause of poor adherence, resulting in disease relapse or drug resistance.
      Therefore, physicians are encouraged to prescribe generic drugs to reduce the
      financial burden of medical expenses. In Japan, only generic drugs that have a
      basic chemical structure and pharmacokinetic data that are the same as those of
      the original drug are approved. However, it is not mandatory to demonstrate that
      generic drugs have adequate biological effects. This is one of the reasons why
      Japanese hematologists do not often use generic IM. The aim of the present study
      was to compare the anti-leukemic effects of GlivecTM (a commercial IM) and its
      generic formulation, OHK9511. The IC50 values of OHK9511 and GlivecTM were
      comparable, and both induced similar levels of apoptosis in several CML cell
      lines. Furthermore, the overall survival of OHK9511-treated mice transplanted
      with BCR-ABL-positive cells was similar to that of mice treated with GlivecTM.
      Although the experiments performed herein were basic, the results suggest that
      physicians should consider using generic IM. 

PMID- 25757923
TI  - Relationship between the concentration of anti-polyethylene glycol (PEG)
      immunoglobulin M (IgM) and the intensity of the accelerated blood clearance (ABC)
      phenomenon against PEGylated liposomes in mice.
AB  - PEGylation, which is the surface modification of nanocarriers with polyethylene
      glycol (PEG), has increased the circulation time and reduced the immunogenic
      responses to nanocarriers. However, many reports have demonstrated that the
      intravenous injection of sterically stabilized PEGylated liposome (SL) causes an
      accelerated blood clearance (ABC) of subsequent doses via anti-PEG immunoglobulin
      M (IgM)-mediated complement activation. In the present study, the relationships
      between serum anti-PEG IgM concentration, the intensity of complement activation
      and the hepatic clearance of SL were quantitatively investigated for their role
      in the ABC phenomenon. Interestingly, with increasing serum anti-PEG IgM
      concentrations, the intensity of complement activation increased linearly, while
      the intensity of the hepatic clearance of SL was increased and then saturated. In
      addition, only 15-17% of anti-PEG IgM in blood circulation induced by SL at
      different doses was associated with a second dose SL. The present results
      indicate that it is the hepatic uptake of SL that is the limiting step in the ABC
      phenomenon, rather than the association of anti-PEG IgM to the SL and a
      subsequent complement activation. 

PMID- 25757924
TI  - Anti-inflammatory actions of herbal formula Gyejibokryeong-hwan regulated by
      inhibiting chemokine production and STAT1 activation in HaCaT cells.
AB  - Gyejibokryeong-hwan (GJBRH; Keishi-bukuryo-gan in Japan and Guizhi Fuling Wan in
      China) is a traditional herbal formula comprising five medicinal herbs and is
      used to treat climacteric syndrome. GJBRH has been shown to exhibit biological
      activity against diabetes, diabetic nephropathy, atherosclerosis, ischemia, and
      cancer. However, there is no scientific evidence of its activities against skin
      inflammation, including atopic dermatitis. We used the HaCaT human keratinocyte
      cell line to investigate the effects of GJBRH on skin inflammation. No
      significant cytotoxicity was observed in cells treated with GJBRH up to a
      concentration of 1000 ug/mL. Exposure to the proinflammatory cytokines tumor
      necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma) significantly
      increased HaCaT cell production of the following chemokines: macrophage-derived
      chemokine (MDC)/CCL22; regulated on activation, normal T-cell expressed and
      secreted (RANTES)/CCL5; and interleukin-8 (IL-8). In contrast, GJBRH
      significantly reduced the production of MDC, RANTES, and IL-8 compared with
      control cells simulated with TNF-alpha and IFN-gamma. Consistently, GJBRH
      suppressed the mRNA expression of MDC, RANTES, and IL-8 in TNF-alpha and IFN
      gamma-treated cells. Treatment with GJBRH markedly inhibited phosphorylation of
      signal transducer and activator of transcription 1 (STAT1) in HaCaT cells
      stimulated with TNF-alpha and IFN-gamma. Our findings indicate that GJBRH impairs
      TNF-alpha and IFN-gamma-mediated inflammatory chemokine production and STAT1
      phosphorylation in keratinocytes. We suggest that GJBRH may be a potent
      therapeutic agent for inflammatory skin disorders. 

PMID- 25757925
TI  - Induction of epithelial-mesenchymal transition and down-regulation of miR-200c
      and miR-141 in oxaliplatin-resistant colorectal cancer cells.
AB  - Epithelial-mesenchymal transition (EMT) and changes in the expression of the
      microRNA-200 (miR-200) family were examined in the human colorectal cancer (CRC)
      cell line SW620 with acquired oxaliplatin (L-OHP) resistance. Two CRC cell lines,
      SW480, derived from primary CRC, and SW620, derived from lymph node metastasis,
      which were obtained from the same patient, were used in the present study. L-OHP
      resistant SW620 cells were obtained by exposure to L-OHP for 155 d. The
      concentration of L-OHP was increased to 80 uM in a stepwise manner. The IC50
      value of L-OHP was increased 16-fold in L-OHP-resistant SW620 cells, which also
      displayed mesenchymal cell-like characteristics, such as the down-regulation of E
      cadherin and up-regulation of vimentin. However, L-OHP-resistant SW480 cells were
      not obtained when the concentration of L-OHP was increased in a similar stepwise
      manner. The expression levels of members of the miR-200 family (miR-200a, miR
      200b, miR-429, miR-200c, and miR-141) were significantly higher in SW480 cells
      than in SW620 cells. The expression levels of miR-200c and miR-141 were
      significantly lower in L-OHP-resistant SW620 cells than in control SW620 cells. L
      OHP-resistant SW620 cells did not exhibit cross-resistance to other anti-cancer
      drugs used to treat CRC, such as 5-fluorouracil, irinotecan, and the active
      metabolite of irinotecan (SN-38). These results suggest that the down-regulated
      expression of miR-200c and miR-141 plays a role in selective resistance to L-OHP
      and EMT in CRC cells during repeated treatments with L-OHP. 

PMID- 25757926
TI  - In vitro inhibition of CYP2C9-mediated warfarin 7-hydroxylation by iguratimod:
      possible mechanism of iguratimod-warfarin interaction.
AB  - Iguratimod is a novel disease-modifying antirheumatic drug. A blue letter (safety
      advisory) for drug interaction between iguratimod and warfarin was issued by the
      Ministry of Health, Labour and Welfare of Japan in May 2013. Iguratimod may
      affect warfarin metabolism catalyzed by CYP. However, it is not clear whether
      iguratimod inhibits warfarin oxidation. This study was performed to investigate
      the effects of iguratimod on warfarin 7-hydroxylation with human liver microsomes
      (HLMs) and recombinant CYP enzymes. Iguratimod concentration-dependently
      inhibited R,S-warfarin 7-hydroxylase activity of HLMs with an IC50 value of 15.2
      uM. The inhibitory effect was examined with S-warfarin and R-warfarin to
      determine which enantiomer was more potently inhibited by iguratimod. Iguratimod
      potently inhibited the S-warfarin 7-hydroxylase activity of HLMs with an IC50
      value of 14.1 uM, but showed only slight inhibition of R-warfarin 7
      hydroxylation. Furthermore, iguratimod inhibited the S-warfarin 7-hydroxylase
      activity of recombinant CYP2C9.1 (rCYP2C9.1) and rCYP2C9.3 in a concentration
      dependent manner with IC50 values of 10.8 and 20.1 uM, respectively. Kinetic
      analysis of the inhibition of S-warfarin 7-hydroxylation by iguratimod indicated
      competitive-type inhibition for HLMs and rCYP2C9.1 but mixed-type inhibition for
      rCYP2C9.3. The Ki values for HLMs, rCYP2C9.1, and rCYP2C9.3 were 6.74, 4.23, and
      14.2 uM, respectively. Iguratimod did not exert metabolism-dependent inhibition
      of S-warfarin 7-hydroxylation. These results indicated that iguratimod is a
      potent direct inhibitor of CYP2C9-mediated warfarin 7-hydroxylation and that its
      inhibitory effect on CYP2C9.1 was more sensitive than that on CYP2C9.3. 

PMID- 25757927
TI  - Serotonin regulates beta-casein expression via 5-HT7 receptors in human mammary
      epithelial MCF-12A cells.
AB  - We previously reported that serotonin (5-hydroxytryptamine; 5-HT) suppresses beta
      casein expression, a differentiation marker in mammary epithelial cells, via
      inhibition of the signal transducer and activator of transcription 5 (STAT5)
      phosphorylation in the human mammary epithelial cell line, MCF-12A. In this
      study, we investigated the expression pattern of the different 5-HT receptor
      subtypes in MCF-12A cells, and identified the receptors involved in 5-HT-mediated
      suppression of beta-casein protein expression. beta-Casein mRNA expression was
      inhibited by 30 uM 5-HT in a time-dependent manner. Treatment with 30 uM 5-HT for
      72 h decreased beta-casein protein levels and STAT5 phosphorylation (pSTAT5). The
      cells expressed four 5-HT receptors subtypes (5-HTR1D, 2B, 3A, and 7) at the mRNA
      and protein level, and their expression was elevated by prolactin (PRL)
      treatment. Additionally, the mRNA levels of 5-HTR1D and 5-HTR7 were significantly
      higher than the other 5-HT receptors in the cells. Tryptophan hydroxylase 1 mRNA
      was detectable in the cells in the absence of PRL, and PRL treatment
      significantly increased its expression. beta-Casein and pSTAT5/STAT5 levels in
      the cells co-treated with 5-HT and a selective 5-HTR1D inhibitor, BRL15572, were
      equal to those observed in cells treated with 5-HT alone. However, in the cells
      co-treated with 5-HT and a selective 5-HTR7 inhibitor, SB269970, beta-casein and
      pSTAT5/STAT5 levels increased in a SB269970 concentration-dependent manner. In
      conclusion, we showed that 5-HT regulates beta-casein expression via 5-HTR7 in
      MCF-12A human mammary epithelial cells. 

PMID- 25757928
TI  - Effects of menthol on the pharmacokinetics of triazolam and phenytoin.
AB  - We have previously shown that menthol attenuates the anticoagulant effect of
      warfarin by increasing the expression levels of CYP3A and CYP2C in the liver.
      This study evaluated the effects of menthol on the pharmacokinetics of the CYP3A
      substrate triazolam and the CYP2C substrate phenytoin. Menthol was orally
      administered to mice for 7 d. Twenty-four hours after the administration of
      menthol, triazolam was orally administered, and the plasma concentration was
      measured. In addition, the CYP3A metabolic activity for triazolam and the CYP3A
      expression level in the liver were determined. The effects of menthol on the
      pharmacokinetics of phenytoin were assessed in the same manner. In the menthol
      treated group, the area under the blood concentration-time curve (AUC) of
      triazolam was lower and its clearance was higher compared with the control group.
      The CYP3A metabolic activity and CYP3A expression level in the liver were
      significantly increased in the menthol-treated group compared with the control
      group. Similarly, the AUC of phenytoin was lower and the hepatic CYP2C expression
      level was higher in the menthol-treated group. Thus, menthol lowered the plasma
      concentrations of triazolam and phenytoin when concurrently administered. These
      effects may be attributed to an increased metabolic activity for these drugs due
      to the increased expression of CYP3A and CYP2C in the liver. 

PMID- 25757929
TI  - Liposomal pemetrexed: formulation, characterization and in vitro cytotoxicity
      studies for effective management of malignant pleural mesothelioma.
AB  - Pemetrexed (PMX) is a newly developed multi-targeted anti-folate with promising
      clinical activity in many solid tumors including malignant pleural mesothelioma
      (MPM). However, PMX does not show sufficient anti-tumor activity in vivo when
      used alone either due to inefficient delivery of adequate concentrations to tumor
      tissue or dose-limiting side effects. In order to overcome these problems and to
      achieve potent anti-tumor activity, PMX was encapsulated into a liposomal
      delivery system. In the present study, various formulations of liposomal PMX were
      prepared. The effect of formulation parameters on the encapsulation efficiency of
      PMX within liposomes was evaluated. In addition, the influence of drug release
      rate on the in vitro cytotoxicity was investigated. Encapsulation of PMX within
      liposomes was remarkably increased by the incorporation of cholesterol within
      liposomal membranes and by increasing the total lipid concentration.
      Encapsulation efficiency was found to be unaffected by the type of phospholipid
      used or the inclusion of a cation lipid, DC-6-14. Interestingly, encapsulation of
      PMX within "fluid" liposomes was found to allow efficient release of PMX from
      liposomes resulting in a potent in vitro cytotoxicity against MPM MSTO-211H cell
      line. On the other hand, entrapment of PMX within "solid" liposomes substantially
      hindered PMX release from liposomes, and thus PMX failed to exert any in vitro
      cytotoxicity. These results suggest that encapsulation of PMX within "fluid"
      liposomes might represent a novel strategy to enhance the therapeutic efficacy of
      PMX while minimizing the side effect encountered by the non selective delivery of
      free PMX to various body tissues. 

PMID- 25757930
TI  - Metabolic changes in paraquat poisoned patients and support vector machine model
      of discrimination.
AB  - Numerous people die of paraquat (PQ) poisoning every year in the world. Although
      several studies regarding paraquat (PQ) poisoning have been conducted, the
      metabolic changes in plasma remain unknown. In this study, the metabolomics of 15
      PQ poisoned patients with plasma PQ concentrations in excess of 0.1 ug/mL and 16
      healthy volunteers were investigated. The plasma samples were evaluated through
      the use of gas chromatography-mass spectrometry (GC/MS) and analyzed by partial
      least-squares discriminant analysis (PLS-DA). Based on the metabolomics data, a
      support vector machine (SVM) discrimination model was developed. The results
      showed the plasma levels of urea, glucose oxime and L-phenylalanine decreased and
      cholesterol increased in PQ poisoned patients in comparison to healthy
      volunteers. The SVM discrimination model was developed, and performed with a high
      degree of accuracy, to distinguish PQ poisoned patients from healthy volunteers.
      In conclusion, metabolic pathways including the urea cycle, and amino acid,
      glucose, and cholesterol metabolism were impaired after PQ poisoning. An SVM
      discrimination model, based on metabolomics data, was established and may become
      a new powerful tool for the diagnosis of PQ poisoning. 

PMID- 25757931
TI  - Structure-dependent inhibitory effects of green tea catechins on insulin
      secretion from pancreatic beta-cells.
AB  - The effects of green tea catechins on glucose-stimulated insulin secretion (GSIS)
      were investigated in the beta-cell line INS-1D. Epigallocatechin gallate (EGCG)
      at 10 uM or gallocatechin gallate (GCG) at 30 uM caused significant inhibitory
      effects on GSIS, and each of these at 100 uM almost abolished it. In contrast,
      epicatechin (EC) or catechin (CA) had no effect on GSIS at concentrations up to
      100 uM. We thus investigated the structure-activity relationship by using
      epigallocatechin (EGC) and gallocatechin (GC) containing a trihydroxyl group in
      the B-ring, and epicatechin gallate (ECG) and catechin gallate (CG) containing
      the gallate moiety. EGC, GC, and ECG caused an inhibition of GSIS, although
      significant effects were obtained only at 100 uM. At this concentration, EGC
      almost abolished GSIS, whereas GC and ECG partially inhibited it. In contrast, CG
      did not affect GSIS at concentrations up to 100 uM. EGCG also abolished the
      insulin secretion induced by tolbutamide, an ATP-sensitive K(+) channel blocker,
      and partially inhibited that induced by 30 mM K(+). Moreover, EGCG, but not EC,
      inhibited the oscillation of intracellular Ca(2+) concentration induced by 11.1
      mM glucose. These results suggest that some catechins at supraphysiological
      concentrations have inhibitory effects on GSIS, the potency of which depends on
      their structure; the order of potency was EGCG>GCG>EGC>GC~ECG. The inhibitory
      effects seem to be mediated by the inhibition of voltage-dependent Ca(2+)
      channels, which is caused, at least in part, by membrane hyperpolarization
      resulting from the activation of K(+) channels. 

PMID- 25757932
TI  - ISG15 regulates RANKL-induced osteoclastogenic differentiation of RAW264 cells.
AB  - Interferon-stimulated gene 15 kDa (ISG15) is a protein upregulated by interferon
      beta that negatively regulates osteoclastogenesis. We investigated the role of
      ISG15 in receptor activator of nuclear factor-kappaB ligand (RANKL)-induced
      osteoclastogenic differentiation of murine RAW264 cells. RANKL stimulation
      induced ISG15 expression in RAW264 cells at both the mRNA and protein levels.
      Overexpression of ISG15 in RAW264 cells resulted in suppression of cell fusion in
      RANKL-stimulated cells as well as the reduced expression of ATP6v0d2, a gene
      essential for cell fusion in osteoclastogenic differentiation. These results
      suggest that ISG15 suppresses RANKL-induced osteoclastogenesis, at least in part,
      through inhibition of ATP6v0d2 expression. 

PMID- 25757933
TI  - Direct radical scavenging activity of benzbromarone provides beneficial
      antioxidant properties for hyperuricemia treatment.
AB  - Uric acid exerts an important antioxidant effect against external oxidative
      stress under physiological conditions. However, uric acid itself can increase
      oxidative stress via reduced nicotinamide adenine dinucleotide phosphate (NADPH)
      oxidase activation in adipocytes and vascular cells. Uric acid transporter 1 is
      involved in the generation of this oxidative stress. Furthermore, uric acid
      locally activates the renin-angiotensin system, thus producing angiotensin II and
      subsequently increasing intracellular oxidative stress. Benzbromarone has been
      reported to suppress uric acid reabsorption via uric acid transporter 1
      inhibition in renal tubular cells. In this study we evaluated the in vitro
      antioxidant effect of benzbromarone from several perspectives. First, the direct
      radical-trapping capacity of benzbromarone was measured by chemiluminescence
      assay and electron paramagnetic resonance spectroscopy. Second, the intracellular
      antioxidant activity of benzbromarone in hyperuricemia was evaluated using
      endothelial cells. In light of these results, benzbromarone is hypothesized
      directly to scavenge the superoxide anion radical. In addition, benzbromarone
      inhibited reactive oxygen species production that was induced by angiotensin II
      or uric acid in endothelial cells. These findings suggest that benzbromarone
      possesses the ability directly to scavenge radicals and may act as an antioxidant
      against uric acid and angiotensin II-induced oxidative stresses in endothelial
      cells at therapeutically achievable levels in blood. 

PMID- 25757934
TI  - Antibacterial drug treatment increases intestinal bile acid absorption via
      elevated levels of ileal apical sodium-dependent bile acid transporter but not
      organic solute transporter alpha protein.
AB  - Antibacterial drug treatment increases the bile acid pool size and hepatic bile
      acid concentration through the elevation of hepatic bile acid synthesis. However,
      the involvement of intestinal bile acid absorption in the increased bile acid
      pool size remains unclear. To determine whether intestinal bile acid absorption
      contributes to the increased bile acid pool in mice treated with antibacterial
      drugs, we evaluated the levels of bile acid transporter proteins and the capacity
      of intestinal bile acid absorption. Ileal apical sodium-dependent bile acid
      transporter (ASBT) mRNA and protein levels were significantly increased in
      ampicillin (ABPC)-treated mice, whereas organic solute transporter alpha
      (OSTalpha) mRNA levels, but not protein levels, significantly decreased in mice.
      Similar alterations in the expression levels of bile acid transporters were
      observed in mice treated with bacitracin/neomycin/streptomycin. The capacity for
      intestinal bile acid absorption was evaluated by an in situ loop method.
      Increased ileal absorption of taurochenodeoxycholic acid was observed in mice
      treated with ABPC. These results suggest that intestinal bile acid absorption is
      elevated in an ASBT-dependent manner in mice treated with antibacterial drugs. 

PMID- 25757935
TI  - The osteogenic response of mesenchymal stromal cells to strontium-substituted
      bioactive glasses.
AB  - Bioactive glasses are known to stimulate bone healing, and the incorporation of
      strontium has the potential to increase their potency. In this study, calcium
      oxide in the 45S5 bioactive glass composition was partially (50%, Sr50) or fully
      (100%, Sr100) substituted with strontium oxide on a molar basis. The effects of
      the substitution on bioactive glass properties were studied, including density,
      solubility, and in vitro cytotoxicity. Stimulation of osteogenic differentiation
      was investigated using mesenchymal stromal cells obtained from rat bone marrow.
      Strontium substitution resulted in altered physical properties including
      increased solubility. Statistically significant reductions in cell viability were
      observed with the addition of bioactive glass powders to culture medium.
      Specifically, addition of >= 13.3 mg/ml of 45S5 bioactive glass or Sr50, or >=
      6.7 mg/ml of Sr100, resulted in significant inhibition. Real-time PCR analyses
      detected the upregulation of genes associated with osteoblastic differentiation
      in the presence of all bioactive glass compositions. Some genes, including Alpl
      and Bglap, were further stimulated in the presence of Sr50 and Sr100. It was
      concluded that strontium-substituted bioactive glasses promoted osteogenesis in a
      differentiating bone cell culture model and, therefore, have considerable
      potential for use as improved bioactive glasses for bone tissue regeneration.

PMID- 25757936
TI  - Digital ethnography and the social dimension of introspection: an empirical study
      in two Colombian schools.
AB  - We developed a teaching-led research project to empirically ground methodological
      reflection about digital ethnography. Drawing on Cordelois' collective
      ethnographic observation approach, fifteen emerging professionals (from a private
      general education university and a Police Academy in Bogota) collaborated in a
      method seminar on digital ethnography. They worked in cross-institutional
      research teams, each carrying SenseCams for 3 days. Students had a dual role as
      both participants and observers during self-confrontation interviews. The
      research design enabled emerging professionals to introspect about what it is to
      be a member of their institution. The SenseCam provided an additional opportunity
      for observation as it elicited different reactions in the two institutions. The
      fact that SenseCams produce sequential accounts of activity as well as its
      situated nature made apparent the autonomy to study and solve daily issues (e.g.
      transport, security, commitments) by students from the university, while students
      in the police academy are more focused on responding to unforeseen activities
      (e.g. police services, unexpected requests). Finally, our research highlights the
      relevance of the social dimension of introspection for digital ethnography. How
      digital data that captures an individual perspective is negotiated in a group
      becomes a key methodological question.

PMID- 25757937
TI  - T wave inversions in athletes: a variety of scenarios.
AB  - Athletic intensive exercise is associated with repolarization changes affecting
      the ST-segment and T-wave morphology. The prevalence and distribution of these
      alterations are influenced by several demographic factors. One of the most
      challenging conundrums for both the cardiologist and the sports medicine
      physician is the correct interpretation of these repolarization changes to
      prevent an erroneous diagnosis with potentially serious consequences. A 12-lead
      electrocardiogram (ECG) demonstrating inverted T-waves may represent the first
      and only sign of such inherited heart muscle diseases, and may precede the
      detection of any structural changes in the heart, however, T-wave inversion in
      leads V1-V4 in black athletes may represent ethnic variation which is exaggerated
      by exercise.

PMID- 25757938
TI  - Paroxysmal nocturnal haemoglobinuria: to prednisone or not to prednisone?--a case
      report of a patient previously treated with steroids for 15 yrs and significant
      response on eculizumab.
AB  - BACKGROUND: Paroxysmal nocturnal haemoglobinuria (PNH) is a rare acquired
      haematopoietic stem cell disorder characterised by persistent haemolysis and
      platelet activation, severe end-organ damage, an increased risk of thrombosis and
      early mortality. We present the case of a 56-year-old male with long-standing PNH
      and significant disease-related morbidity who underwent steroid therapy for
      approximately 15 yrs before treatment with eculizumab, a humanized monoclonal
      antibody that blocks the terminal phase of the complement cascade at the C5
      level. CASE HISTORY: The patient presented with a severely impaired quality of
      life in 1997 and was diagnosed with PNH 8 months later, soon after which he was
      commenced on steroid therapy with prednisone. During long-term steroid therapy
      with progressive increases in prednisone dose, the patient had frequent
      haemolytic episodes as well as thrombosis and renal complications. He also
      experienced Cushing's syndrome with arterial hypertension, insulin-dependent
      diabetes mellitus, osteoporosis, acne and portal fibrosis. Eculizumab therapy was
      started in late-2009 and led to rapid improvements in haemoglobin and lactate
      dehydrogenase levels with a complete cessation of haemolytic episodes. Eculizumab
      has been well tolerated. CONCLUSIONS: Long-term steroid therapy was not effective
      in controlling PNH in this patient and was associated with significant
      comorbidities. Treatment with eculizumab led to major improvements, even after
      such a long period with relatively uncontrolled disease.

PMID- 25757940
TI  - Sample size determination for testing nonequality under a three-treatment two
      period incomplete block crossover trial.
AB  - To reduce the lengthy duration of a crossover trial for comparing three
      treatments, the incomplete block design has been often considered. A sample size
      calculation procedure for testing nonequality between either of the two
      experimental treatments and a placebo under such a design is developed. To
      evaluate the performance of the proposed sample size calculation procedure, Monte
      Carlo simulation is employed. The accuracy of the sample size calculation
      procedure developed here is demonstrated in a variety of situations. As compared
      with the parallel groups design, a substantial proportional reduction in the
      total minimum required sample size in use of the incomplete block crossover
      design is found. A crossover trial comparing two different doses of formoterol
      with a placebo on the forced expiratory volume is applied to illustrate the use
      of the sample size calculation procedure.

PMID- 25757939
TI  - In vivo CaspaseTracker biosensor system for detecting anastasis and non-apoptotic
      caspase activity.
AB  - The discovery that mammalian cells can survive late-stage apoptosis challenges
      the general assumption that active caspases are markers of impending death.
      However, tools have not been available to track healthy cells that have
      experienced caspase activity at any time in the past. Therefore, to determine if
      cells in whole animals can undergo reversal of apoptosis, known as anastasis, we
      developed a dual color CaspaseTracker system for Drosophila to identify cells
      with ongoing or past caspase activity. Transient exposure of healthy females to
      environmental stresses such as cold shock or starvation activated the
      CaspaseTracker coincident with caspase activity and apoptotic morphologies in
      multiple cell types of developing egg chambers. Importantly, when stressed flies
      were returned to normal conditions, morphologically healthy egg chambers and new
      progeny flies were labeled by the biosensor, suggesting functional recovery from
      apoptotic caspase activation. In striking contrast to developing egg chambers,
      which lack basal caspase biosensor activation under normal conditions, many adult
      tissues of normal healthy flies exhibit robust caspase biosensor activity in a
      portion of cells, including neurons. The widespread persistence of CaspaseTracker
      positivity implies that healthy cells utilize active caspases for non-apoptotic
      physiological functions during and after normal development. 

PMID- 25757941
TI  - Attention and normalization circuits in macaque V1.
AB  - Attention affects neuronal processing and improves behavioural performance. In
      extrastriate visual cortex these effects have been explained by normalization
      models, which assume that attention influences the circuit that mediates surround
      suppression. While normalization models have been able to explain attentional
      effects, their validity has rarely been tested against alternative models. Here
      we investigate how attention and surround/mask stimuli affect neuronal firing
      rates and orientation tuning in macaque V1. Surround/mask stimuli provide an
      estimate to what extent V1 neurons are affected by normalization, which was
      compared against effects of spatial top down attention. For some
      attention/surround effect comparisons, the strength of attentional modulation was
      correlated with the strength of surround modulation, suggesting that attention
      and surround/mask stimulation (i.e. normalization) might use a common mechanism.
      To explore this in detail, we fitted multiplicative and additive models of
      attention to our data. In one class of models, attention contributed to
      normalization mechanisms, whereas in a different class of models it did not.
      Model selection based on Akaike's and on Bayesian information criteria
      demonstrated that in most cells the effects of attention were best described by
      models where attention did not contribute to normalization mechanisms. This
      demonstrates that attentional influences on neuronal responses in primary visual
      cortex often bypass normalization mechanisms. 

PMID- 25757943
TI  - Correction. The Canadian survey of health, lifestyle and ageing with multiple
      sclerosis: methodology and initial results.

PMID- 25757942
TI  - Soluble plasma VE-cadherin concentrations are elevated in patients with STEC
      infection and haemolytic uraemic syndrome: a case-control study.
AB  - OBJECTIVES: To investigate whether the adherens junction protein vascular
      endothelial cadherin (VE-cadherin) is released during Shiga toxin 2 producing
      Escherichia coli (STEC) infection with haemolytic uraemic syndrome (HUS) and thus
      could be used to assist diagnosis. DESIGN: Using data from the large 2011 STEC
      outbreak in northern Europe, we determined VE-cadherin plasma concentrations in
      356 patients distributed over three patient cohorts: patients with STEC infection
      accompanied by HUS (STEC-HUS), STEC patients without HUS (STEC) and control
      patients with diarrhoea but without STEC infection. We then looked for
      associations between VE-cadherin concentrations and disease severity defined by
      changes in lactate dehydrogenase, haemoglobin, creatinine, platelet count,
      haptoglobin and neurological symptoms. SETTING: This study was conducted at the
      University Medical Center Hamburg-Eppendorf, Germany. PARTICIPANTS: 79 STEC-HUS
      patients, 77 STEC patients and 200 control patients were enrolled in the study.
      RESULTS: We analysed 864 specimens (207 STEC, 449 STEC-HUS and 208 controls) in
      total. At admission, VE-cadherin concentration tended to be lower in STEC-HUS
      patients compared to other patients. However, HUS patients later showed an
      increase in VE-cadherin concentrations with prolonged elevation beyond remission.
      This pattern clearly differs from that observed in non-HUS patients. CONCLUSIONS:
      VE-cadherin concentrations are elevated in STEC-HUS patients and might be a
      biomarker reflecting endothelial damage in patients with HUS.

PMID- 25757944
TI  - Cervical cancer screening and HPV vaccine acceptability among rural and urban
      women in Kilimanjaro Region, Tanzania.
AB  - OBJECTIVE: To determine cervical cancer screening coverage and the knowledge,
      attitudes and barriers toward screening tests among women in rural and urban
      areas of Tanzania, as well as explore how they view the acceptability of the HPV
      vaccine and potential barriers to vaccination. SETTING: A cross-sectional study
      using interview-administered questionnaires was conducted using multistage random
      sampling within urban and rural areas in Kilimanjaro Region, Tanzania.
      PARTICIPANTS: Women aged 18-55 were asked to participate in the survey. The
      overall response rate was 97.5%, with a final sample of 303 rural and 272 urban
      dwelling women. PRIMARY AND SECONDARY OUTCOME MEASURES: Descriptive and simple
      test statistics were used to compare across rural and urban strata. Multivariate
      logistic regression models were used to estimate ORs and 95% CIs. RESULTS: Most
      women (82%) reported they had heard of cervical cancer, while self-reported
      cervical cancer screening among women was very low (6%). In urban areas, factors
      associated with screening were: older age (OR=4.14, 95% CI 1.86 to 9.24 for ages
      40-49, and OR=8.38, 95% CI 2.10 to 33.4 for >50 years), having health insurance
      (OR=4.15, 95% CI 1.52 to 11.4), and having knowledge about cervical cancer
      (OR=5.81, 95% CI 1.58 to 21.4). In contrast, among women residing in rural areas,
      only condom use (OR=6.44, 95% CI 1.12 to 37.1) was associated with screening.
      Women from both rural and urban areas had low vaccine-related knowledge; however,
      most indicated they would be highly accepting if it were readily available (93%).
      CONCLUSIONS: The current proportion of women screened for cervical cancer is very
      low in Kilimanjaro Region, and our study has identified several modifiable
      factors that could be addressed to increase screening rates. Although best
      implemented concurrently, the availability of prophylactic vaccination for girls
      may provide an effective means of prevention if they are unable to access
      screening in the future.

PMID- 25757945
TI  - The accuracy of the general practitioner's sense of alarm when confronted with
      dyspnoea and/or thoracic pain: protocol for a prospective observational study.
AB  - INTRODUCTION: Dyspnoea and chest pain are signs shared with multiple pathologies
      ranging from the benign to life-threatening diseases. Gut feelings such as the
      sense of alarm and the sense of reassurance are known to play a substantial role
      in the diagnostic reasoning of general practitioners (GPs). A Gut Feelings
      Questionnaire (GFQ) has been validated to measure the GP's sense of alarm. A
      French version of the GFQ is available following a linguistic validation
      procedure. The aim of the study is to calculate the diagnostic test accuracy of a
      GP's sense of alarm when confronted with dyspnoea and chest pain. METHODS AND
      ANALYSIS: Prospective observational study. Patients aged between 18 and 80 years,
      consulting their GP for dyspnoea and/or thoracic pain will be considered for
      enrolment in the study. These GPs will have to complete the questionnaire
      immediately after the consultation for dyspnoea and/or thoracic pain. The follow
      up and the final diagnosis will be collected 4 weeks later by phone contact with
      the GP or with the patient if their GP has no information. Life-threatening and
      non-life-threatening diseases have previously been defined according to the
      pathologies or symptoms in the (ICPC2) International Collegiate Programming
      Contest classification. Members of the research team, blinded to the actual
      outcomes shown on the index questionnaire, will judge each case in turn and will,
      by consensus, classify the expected outcomes as either life-threatening or non
      life-threatening diseases. The sensitivity, the specificity, the positive and
      negative likelihood ratio of the sense of alarm will be calculated from the
      constructed contingency table. ETHICS AND DISSEMINATION: This study was approved
      by the ethical committee of the University de Bretagne Occidentale. A written
      informed consent form will be signed and dated by GPs and patients at the
      beginning of the study. The results will be published in due course.

PMID- 25757946
TI  - Effectiveness of school-based smoking prevention curricula: systematic review and
      meta-analysis.
AB  - OBJECTIVE: To assess effectiveness of school-based smoking prevention curricula
      keeping children never-smokers. DESIGN: Systematic review, meta-analysis. DATA:
      MEDLINE (1966+), EMBASE (1974+), Cinahl, PsycINFO (1967+), ERIC (1982+), Cochrane
      CENTRAL, Health Star, Dissertation Abstracts, conference proceedings. DATA
      SYNTHESIS: pooled analyses, fixed-effects models, adjusted ORs. Risk of bias
      assessed with Cochrane Risk of Bias tool. SETTING: 50 randomised controlled
      trials (RCTs) of school-based smoking curricula. PARTICIPANTS: Never-smokers age
      5-18 (n=143,495); follow-up >=6 months; all countries; no date/language
      limitations. INTERVENTIONS: Information, social influences, social competence,
      combined social influences/competence and multimodal curricula. OUTCOME MEASURE:
      Remaining a never-smoker at follow-up. RESULTS: Pooling all curricula, trials
      with follow-up <=1 year showed no statistically significant differences compared
      with controls (OR 0.91 (0.82 to 1.01)), though trials of combined social
      competence/social influences curricula had a significant effect on smoking
      prevention (7 trials, OR 0.59 (95% CI 0.41 to 0.85)). Pooling all trials with
      longest follow-up showed an overall significant effect in favour of the
      interventions (OR 0.88 (0.82 to 0.95)), as did the social competence (OR 0.65
      (0.43 to 0.96)) and combined social competence/social influences curricula (OR
      0.60 (0.43 to 0.83)). No effect for information, social influences or multimodal
      curricula. Principal findings were not sensitive to inclusion of booster sessions
      in curricula or to whether they were peer-led or adult-led. Differentiation into
      tobacco-only or multifocal curricula had a similar effect on the primary
      findings. Few trials assessed outcomes by gender: there were significant effects
      for females at both follow-up periods, but not for males. CONCLUSIONS: RCTs of
      baseline never-smokers at longest follow-up found an overall significant effect
      with average 12% reduction in starting smoking compared with controls, but no
      effect for all trials pooled at <=1 year. However, combined social
      competence/social influences curricula showed a significant effect at both follow
      up periods. SYSTEMATIC REVIEW REGISTRATION: Cochrane Tobacco Review Group
      CD001293.

PMID- 25757947
TI  - Study protocol for a randomised, double-blinded, placebo-controlled, clinical
      trial of S-ketamine for pain treatment in patients with chronic pancreatitis
      (RESET trial).
AB  - INTRODUCTION: Chronic pancreatitis (CP) is an inflammatory disease that causes
      irreversible damage to pancreatic tissue. Pain is its most prominent symptom. In
      the absence of pathology suitable for endoscopic or surgical interventions, pain
      treatment usually includes opioids. However, opioids often have limited efficacy.
      Moreover, side effects are common and bothersome. Hence, novel approaches to
      control pain associated with CP are highly desirable. Sensitisation of the
      central nervous system is reported to play a key role in pain generation and
      chronification. Fundamental to the process of central sensitisation is abnormal
      activation of the N-methyl-D-aspartate receptor, which can be antagonised by S
      ketamine. The RESET trial is investigating the analgaesic and antihyperalgesic
      effect of S-ketamine in patients with CP. METHODS AND ANALYSIS: 40 patients with
      CP will be enrolled. Patients are randomised to receive 8 h of intravenous S
      ketamine followed by oral S-ketamine, or matching placebo, for 4 weeks. To
      improve blinding, 1 mg of midazolam will be added to active and placebo
      treatment. The primary end point is clinical pain relief as assessed by a daily
      pain diary. Secondary end points include changes in patient-reported outcome
      measures, opioid consumption and rates of side effects. The end points are
      registered through the 4-week medication period and for an additional follow-up
      period of 8 weeks to investigate long-term effects. In addition, experimental
      pain measures also serves as secondary end points, and neurophysiological imaging
      parameters are collected. Furthermore, experimental baseline recordings are
      compared to recordings from a group of healthy controls to evaluate general
      aspects of pain processing in CP. ETHICS AND DISSEMINATION: The protocol is
      approved by the North Denmark Region Committee on Health Research Ethics (N
      20130040) and the Danish Health and Medicines Authorities (EudraCT number: 2013
      003357-17). The results will be disseminated in peer-reviewed journals and at
      scientific conferences. TRIAL REGISTRATION NUMBER: The study is registered at
      http://www.clinicaltrialsregister.eu (EudraCT number 2013-003357-17).

PMID- 25757948
TI  - Cost-effectiveness of interventions to control cardiovascular diseases and type 2
      diabetes mellitus in South Asia: protocol for a systematic review.
AB  - INTRODUCTION: While a number of strategies are being implemented to control
      cardiovascular diseases (CVDs) and type 2 diabetes mellitus (T2DM), the cost
      effectiveness of these in the South Asian context has not been systematically
      evaluated. We aim to systematically review the economic (cost-effectiveness)
      evidence available on the individual-, group- and population-level interventions
      for control of CVD and T2DM in South Asia. METHODS AND ANALYSIS: This review will
      consider all relevant economic evaluations, either conducted alongside randomised
      controlled trials or based on decision modelling estimates. These studies must
      include participants at risk of developing CVD/T2DM or with established disease
      in one or more of the South Asian countries (India, Bangladesh, Pakistan, Sri
      Lanka, Nepal, Maldives, Bhutan and Afghanistan). We will identify relevant papers
      by systematically searching all major databases and registries. Selected articles
      will be screened by two independent researchers. Methodological quality of the
      studies will be assessed using a modified Drummond and a Phillips checklist.
      Cochrane guidelines will be followed for bias assessment in the effectiveness
      studies. RESULTS: Results will be presented in line with the PRISMA (Preferred
      Reporting Items for Systematic review and Meta-analysis) checklist, and overall
      quality of evidence will be presented as per the GRADE (Grades of Recommendation,
      Assessment, Development and Evaluation) approach. ETHICS AND DISSEMINATION: The
      study has received ethics approval from the All India Institute of Medical
      Sciences, New Delhi, India. The results of this review will provide policy
      relevant recommendations for the uptake of cost-effectiveness evidence in
      prioritising decisions on essential chronic disease care packages for South Asia.
      STUDY REGISTRATION NUMBER: PROSPERO CRD42013006479.

PMID- 25757949
TI  - VAlidation of an 8-item-questionnaire predictive for a positive caLprotectin tEst
      and Real-life implemenTation in primary care to reduce diagnostic delay in
      inflammatory bowel disease (ALERT): protocol for a prospective diagnostic study.
AB  - INTRODUCTION: Diagnosis of inflammatory bowel disease (IBD) in primary healthcare
      is challenging and often associated with a considerable diagnostic delay. This
      delay is associated with worse disease progression and outcomes. Although testing
      for faecal calprotectin is a useful screening tool to identify patients who need
      endoscopy for IBD, the widespread use may not be appropriate due to the low
      prevalence of patients with IBD among all patients attending a general
      practitioner (GP) with gastrointestinal symptoms. To increase the appropriate
      application of the faecal calprotectin test, an 8-item questionnaire, the
      CalproQuest, has been developed to increase pretest probability for a positive
      test result. METHODS AND ANALYSIS: This is a prospective diagnostic trial. The
      study consists of two independent and consecutive parts A and B, conducted by
      gastroenterologists (A) and GPs (B), respectively. Patients included in part A
      are referred to the gastroenterologist for any endoscopic evaluation. Patients
      included in part B present at their GP because of ongoing unspecific
      gastrointestinal symptoms (abdominal pain, bloating, stool irregularities,
      diarrhoea) for at least 2 weeks. CalproQuest consists of four main and four
      secondary questions specific for IBD; it is considered positive if >=2 main
      criteria are answered positively or one main criterion and two secondary criteria
      are answered positively. In part A, the sensitivity and specificity of
      CalproQuest for stool calprotectin levels >=50 MUg/g faeces and for positive IBD
      diagnosis will be investigated. In part B, the feasibility of CalproQuest in
      daily primary healthcare practice will be assessed. ETHICS AND DISSEMINATION: The
      study protocol was approved by the Ethics Committee of the Kanton Zurich
      (reference KEK-ZH-number 2013-0516). The results will be published in a peer
      reviewed journal and shared with the worldwide medical community. TRIAL
      REGISTRATION NUMBER: ISRCTN66310845.

PMID- 25757951
TI  - Supplements for weight loss: hype or help for obesity? Part II. The inside scoop
      on green coffee bean extract.

PMID- 25757950
TI  - A cross-sectional study of shift work, sleep quality and cardiometabolic risk in
      female hospital employees.
AB  - OBJECTIVES: Investigating the potential pathways linking shift work and
      cardiovascular diseases (CVD), this study aimed to identify whether sleep
      disturbances mediate the relationship between shift work and the metabolic
      syndrome, a cluster of CVD risk factors. DESIGN: Cross-sectional study. SETTING:
      A tertiary-level, acute care teaching hospital in Southeastern Ontario, Canada.
      PARTICIPANTS: Female hospital employees working a shift schedule of two 12 h
      days, two 12 h nights, followed by 5 days off (n=121) were compared with female
      day-only workers (n=150). PRIMARY AND SECONDARY OUTCOME MEASURES: Each of the
      seven components of the Pittsburgh Sleep Quality Index (PSQI) was measured. Of
      these, PSQI global score, sleep latency and sleep efficiency were examined as
      potential mediators in the relationship between shift work and the metabolic
      syndrome. RESULTS: Shift work status was associated with poor (>5) PSQI global
      score (OR=2.10, 95% CI 1.20 to 3.65), poor (>=2) sleep latency (OR=2.18, 95% CI
      1.23 to 3.87) and poor (>=2) sleep efficiency (OR=2.11, 95% CI 1.16 to 3.84).
      Although shift work was associated with the metabolic syndrome (OR=2.29, 95% CI
      1.12 to 4.70), the measured components of sleep quality did not mediate the
      relationship between shift work and the metabolic syndrome. CONCLUSIONS: Women
      working in a rapid forward rotating shift pattern have poorer sleep quality
      according to self-reported indicators of the validated PSQI and they have a
      higher prevalence of the metabolic syndrome compared with women who work during
      the day only. However, sleep quality did not mediate the relationship between
      shift work and the metabolic syndrome, suggesting that there are other
      psychophysiological pathways linking shift work to increased risk for CVD.

PMID- 25757952
TI  - The zinc-finger transcription factor, Ofi1, regulates white-opaque switching and
      filamentation in the yeast Candida albicans.
AB  - Candida albicans is a major fungal pathogen of humans. The most striking
      biological feature of C. albicans is its phenotypic plasticity, allowing it to
      undergo morphological transitions in response to various environmental cues.
      Transcription factors play critical roles in the regulation of morphological
      transitions. Here, we report the role of opaque and filamentation inducer 1
      (Ofi1), a previously uncharacterized zinc-finger-containing protein encoded by
      the gene orf19.4972, in the regulation of white-opaque switching and filamentous
      growth. Over-expression of OFI1 not only induced white-to-opaque switching but
      also promoted filamentation and invasive growth in C. albicans. Deletion of OFI1
      had no obvious effect on filamentation under the culture conditions tested, while
      deletion of OFI1 reduced the frequency of white-to-opaque switching. We propose
      that Ofi1 functions downstream of Wor1, the master regulator of white-opaque
      switching. However, over-expression of OFI1 in the wor1/wor1 mutant could not
      induce the opaque phenotype, suggesting that Ofi1 does not work alone and other
      transcription factors downstream of Wor1 are also involved in this regulation.
      Given the importance of Ofi1 in the regulation of white-opaque switching and
      filamentation, the present study establishes a new link between these two
      processes. 

PMID- 25757953
TI  - Sirt3-MnSOD axis represses nicotine-induced mitochondrial oxidative stress and
      mtDNA damage in osteoblasts.
AB  - Increasing evidence has suggested an important role played by reactive oxygen
      species in the pathogenesis of osteoporosis. Tobacco smoking is an important risk
      factor for the development of osteoporosis, and nicotine is one of the major
      components in tobacco. However, the mechanism by which nicotine promotes
      osteoporosis is not fully understood. Here, in this study, we found that nicotine
      induced mitochondrial oxidative stress and mitochondrial DNA (mtDNA) damage in
      osteoblasts differentiated from mouse mesenchymal stem cell. The activity of
      MnSOD, one of the mitochondrial anti-oxidative enzymes, was significantly reduced
      by nicotine due to the reduced level of Sirt3. Moreover, it was also found that
      Sirt3 could promote MnSOD activity by deacetylating MnSOD. Finally,
      Mn(III)tetrakis (4-benzoic acid) porphyrin (MnTBAP, a MnSOD mimetic) was found to
      markedly reduce the effect of nicotine on osteoblasts. In summary, Sirt3-MnSOD
      axis was identified as a negative component in nicotine-induced mitochondrial
      oxidative stress and mtDNA damage, and MnTBAP may serve as a potential
      therapeutic drug for osteoporosis.

PMID- 25757954
TI  - Efficacy of gait training using a treadmill with and without visual biofeedback
      in patients after stroke: A randomized study.
AB  - OBJECTIVES: To evaluate the effects of gait training using a treadmill with and
      without visual biofeedback in patients in the late period after stroke, and to
      compare both training methods. DESIGN: A randomized, controlled study. SUBJECTS:
      Fifty people at least 6 months after stroke, randomly enrolled into groups with a
      rehabilitation programme of treadmill training with or without visual
      biofeedback. METHODS: Spatio-temporal gait parameters, walking speed, walking
      distance, self-reliant mobility and functional capacity were evaluated during a
      programme of 10 sessions over 2 weeks. RESULTS: Patients in both groups achieved
      statistically significant improvement. Participants in the intervention group
      revealed a significantly greater improvement in the shortening of the stance
      phase (p = 0.0045) and lengthening of the swing phase of the unaffected limb (p =
      0.0042) and an increase in the unaffected limb cycle length (p = 0.0021). There
      were no significant differences between groups in other spatio-temporal
      parameters of gait or additionally assessed parameters. CONCLUSION: Gait training
      using a treadmill resulted in improvements in the gait and functional capacity of
      patients. The use of biofeedback gives better results in improving gait cycle
      length, duration of gait phases and swing phase speed compared with exercise on a
      treadmill alone.

PMID- 25757955
TI  - Concurrent angiomyolipomas and renal cell neoplasms in patients without tuberous
      sclerosis: a retrospective study.
AB  - Synchronous renal cell neoplasms (RCNs) and angiomyolipomas (AML) occurring in
      the same kidney are rare. The aim of this retrospective study is to investigate
      the incidence and clinicopathological features of concurrent AML and RCN in
      patients without tuberous sclerosis complex (TSC). Partial and radical
      nephrectomy specimens with a diagnosis of RCN and AML from 1995 to May 2013 were
      reviewed. Cases were assessed for histological subtype of AML and RCN,
      topographic relationship between the AML and the RCN, and clinical
      characteristics. A total of 565 RCNs and 19 AMLs were identified. Of 19 cases of
      AML, 9 (47%) were associated with renal tumors. Clear-cell renal cell carcinoma
      (RCC) was the most common malignancy associated with AML (56%). The mean age of
      patients with concomitant AML and RCN was higher than the mean age of patients
      with only AML (58.6 vs 55.5 years). The majority of patients with concomitant AML
      and RCN were female (78%). All concurrent sporadic AMLs were benign. We
      identified one case of bilateral clear-cell RCC with concomitant multiple
      bilateral AMLs in a patient with TSC. 

PMID- 25757956
TI  - Total 25(OH) vitamin D, free 25(OH) vitamin D and markers of bone turnover in
      cirrhotics with and without synthetic dysfunction.
AB  - BACKGROUND & AIMS: Current clinical assays for total 25-hydroxy (OH) vitamin D
      measure vitamin D bound to vitamin D-binding protein (DBP) and albumin plus
      unbound ('free') D. We investigated the relationship between total and free
      25(OH)D with bone metabolism markers in normal (>3.5 g/dl) vs. low (<=3.5 g/dl)
      albumin cirrhotics. METHODS: Eighty-two cirrhotics underwent measurement of free
      and total 25(OH)D by immunoassay, DBP and markers of bone metabolism [intact
      parathyroid hormone (iPTH), C-telopeptide (CTX), bone-specific alkaline
      phosphatase (BSAP), osteocalcin, amino-terminal pro-peptide of type 1-collagen
      (P1NP)]. Pearson's coefficients assessed relevant associations. RESULTS:
      Cirrhotics with low (n = 54) vs. normal (n = 28) albumin had lower total 25(OH)D
      (12.1 vs. 21.7 ng/ml), free 25(OH)D (6.2vs.8.6 pg/ml) and DBP(91.4 vs. 140.3
      MUg/ml) [P < 0.01 for each]. iPTH was similar in low and normal albumin groups
      (33 vs. 28 pg/ml; P = 0.38), although serum CTX(0.46vs.0.28 ng/ml) and BSAP(31.7
      vs. 24.8 MUg/L) were increased (P < 0.01). An inverse relationship was observed
      between total 25(OH)D and iPTH in normal (r = -0.47, P = 0.01) but not low
      albumin cirrhotics (r = 0.07, P = 0.62). Similar associations were seen between
      free 25(OH)D and iPTH(Normal: r = -0.46, P = 0.01; Low: r = -0.03, P = 0.84).
      BSAP, osteocalcin and P1NP were elevated above the normal range in all cirrhotics
      but not consistently associated with total or free 25(OH)D. CONCLUSIONS:
      Cirrhotics with low vs. normal albumin have lower levels of DBP, total and free
      25(OH)D. The expected relationship between total or free 25(OH)D with iPTH was
      observed in normal but not in low albumin cirrhotics, demonstrating that total
      25(OH)D is not an accurate marker of bioactive vitamin D status in cirrhotics
      with synthetic dysfunction. Additional investigation into the role of vitamin D
      supplementation and its impact on bone mineral homoeostasis in this population is
      needed.

PMID- 25757957
TI  - A weighted relative difference accumulation algorithm for dynamic metabolomics
      data: long-term elevated bile acids are risk factors for hepatocellular
      carcinoma.
AB  - Dynamic metabolomics studies can provide a systematic view of the metabolic
      trajectory during disease development and drug treatment and reveal the nature of
      biological processes at metabolic level. To extract important information in a
      systematic time dimension rather than at isolated time points, a weighted method
      based on the means and variations along the time points was proposed and first
      applied to previously published rat model data. The method was subsequently
      extended and applied to prospective metabolomics data analysis of hepatocellular
      carcinoma (HCC). Permutation was employed for noise filtering and false discovery
      rate (FDR) was used for parameter optimization during the feature selection. Long
      term elevated serum bile acids were identified as risk factors for HCC
      development. 

PMID- 25757958
TI  - Untangling visual and proprioceptive contributions to hand localisation over
      time.
AB  - Previous studies showed that self-localisation ability involves both vision and
      proprioception, integrated into a single percept, with the tendency to rely more
      heavily on visual than proprioceptive cues. Despite the increasing evidence for
      the importance of vision in localising the hands, the time course of the
      interaction between vision and proprioception during visual occlusion remains
      unclear. In particular, we investigated how the brain weighs visual and
      proprioceptive information in hand localisation over time when the visual cues do
      not reflect the real position of the hand. We tested three hypotheses: Self
      localisations are less accurate when vision and proprioception are incongruent;
      under the same conditions of incongruence, people first rely on vision and
      gradually revert to proprioception; if vision is removed immediately prior to
      hand localisation, accuracy increases. Sixteen participants viewed a video of
      their hands, under three conditions each undertaken with eyes open or closed:
      Incongruent conditions (right hand movement seen: inward, right hand real
      movement: outward), Congruent conditions (movement seen congruent to real
      movement). The right hand was then hidden from view and participants performed a
      localisation task whereby a moving vertical arrow was stopped when aligned with
      the felt position of their middle finger. A second experiment used identical
      methodology, but with the direction of the arrow switched. Our data showed that,
      in the Incongruent conditions (both with eyes open and closed), participants
      perceived their right hand close to its last seen position. Over time, the
      perceived position of the hand shifted towards the physical position. Closing the
      eyes before the localisation task increased the accuracy in the Incongruent
      condition. Crucially, Experiment 2 confirmed the findings and showed that the
      direction of arrow movement had no effect on hand localisation. Our hypotheses
      were supported: When vision and proprioception were incongruent, participants
      were less accurate and initially relied on vision and then proprioception over
      time. When vision was removed, this shift occurred more quickly. Our findings are
      relevant in understanding the normal and pathological processes underpinning self
      localisation.

PMID- 25757959
TI  - Cortical functioning in children with developmental coordination disorder: a
      motor overflow study.
AB  - This study examined brain activation in children with developmental coordination
      disorder (DCD) to reveal areas that may contribute to poor movement execution
      and/or abundant motor overflow. Using functional magnetic resonance imaging, 13
      boys with DCD (mean age = 9.6 years +/-0.8) and 13 typically developing controls
      (mean age = 9.3 years +/-0.6) were scanned performing two tasks (finger
      sequencing and hand clenching) with their dominant hand, while a four-finger
      motion sensor recorded contralateral motor overflow on their non-dominant hand.
      Despite displaying increased motor overflow on both functional tasks during
      scanning, there were no obvious activation deficits in the DCD group to explain
      the abundant motor overflow seen. However, children with DCD were found to
      display decreased activation in the left superior frontal gyrus on the finger
      sequencing task, an area which plays an integral role in executive and spatially
      oriented processing. Decreased activation was also seen in the left inferior
      frontal gyrus, an area typically active during the observation and imitation of
      hand movements. Finally, increased activation in the right postcentral gyrus was
      seen in children with DCD, which may reflect increased reliance on somatosensory
      information during the execution of complex fine motor tasks.

PMID- 25757960
TI  - Effects of cyclosporine A on the hepatobiliary disposition and hepatic uptake of
      etoposide in an isolated perfused rat liver model.
AB  - PURPOSE: A recirculating isolated perfused rat liver model was used to
      investigate the hepatobiliary disposition of etoposide and the effects of
      cyclosporine A (CyA) on the pattern of drug disposition in the bile and uptake in
      the liver. METHODS: The portal vein, bile duct, and superior vena cava were
      cannulated in four groups of rats. The perfusions were conducted in the control
      group, which only received 10 ug/ml etoposide, and the tested groups which
      received etoposide and CyA in 0.4, 2, and 10 mg/kg doses. Perfusate and bile
      samples were collected up to 180 min. RESULTS: The determination of etoposide in
      the samples and homogenized liver by the high-performance liquid chromatography
      method showed that the administration of CyA led to significant changes in the
      hepatic excretion (E h), hepatic clearance (CL h), and half-life (T 1/2) of
      etoposide in the CyA 2 and 10 mg/kg treatment groups but not in 0.4 mg/kg group.
      The volume of the bile decreased to 64 and 45 % and biliary clearance (CL b) of
      etoposide reduced by 73 and 82 % in 0.4 and 2 mg/kg CyA group, respectively, when
      compared with the control group. CONCLUSIONS: These results demonstrated the dose
      dependant non-specific inhibitory effects of CyA on p-glycoproteins, multidrug
      resistance protein 2, bile salt export pump, and organic anion-transporting
      polypeptide, the drug transporters responsible for etoposide hepatobiliary
      disposition, hepatic uptake, and bile formation in rat.

PMID- 25757962
TI  - [Development strategy on cardiopulmonary resuscitation in China].

PMID- 25757961
TI  - Levels of sirolimus in saliva and blood following oral topical sustained-release
      varnish delivery system application.
AB  - PURPOSE: Sirolimus (rapamycin) is a mammalian target of rapamycin pathway
      blocker. The efficacy of sirolimus is currently studied for its antiproliferative
      properties in various malignancies and particularly in squamous cell carcinoma
      and other oral disorders. Topical application at the oral cavity can augment
      sirolimus availability at the site of action by increasing sirolimus levels in
      saliva and hence efficacy, along with improved safety (low levels in the blood to
      avoid side effects) and compliance. Our purpose was to evaluate the release
      profile and safety of a topical sirolimus sustained-release varnish drug delivery
      system. SUBJECTS AND METHODS: Sirolimus sustained-release varnish drug delivery
      system containing a total of 0.5 mg of the drug was applied to nine healthy male
      volunteers. Saliva and blood levels were determined utilizing mass spectrometry
      and chemiluminescent microparticle immunoassay, respectively. The prolonged
      release profile and safety were evaluated for the oral topical delivery system.
      RESULTS: After the application of the drug delivery system, a sustained-release
      profile was observed in the oral cavity. We have measured moderate sirolimus
      levels for up to 12 h. The safety was confirmed, and systemic sirolimus blood
      levels were negligible. CONCLUSIONS: After an application of sirolimus sustained
      release varnish drug delivery system, prolonged drug levels can be achieved in
      the saliva. The oral topical sirolimus concentrations were potentially
      therapeutic along with minimal systemic exposure. These results broaden the
      potential clinical use of sustained-release oral topical rapalogs.

PMID- 25757963
TI  - [The current status and future development in functional hemodynamic
      surveillance].

PMID- 25757964
TI  - [Evaluation of different revascularization strategies for patients with acute
      myocardial infarction with lesions of multiple coronary arteries after primary
      percutaneous coronary intervention and its economic evaluation].
AB  - OBJECTIVE: To investigate the effect and medical cost of different
      revascularization strategies for acute myocardial infarction (AMI) patients with
      multi-vessel disease (MVD). METHODS: A prospective randomized controlled trial
      (RCT) was conducted. From January 2009 to June 2012, patients with AMI and MVD
      undergoing primary percutaneous coronary intervention (PCI) were enrolled. They
      were randomly assigned to group A [staged PCI for non-infarction related artery
      (non-IRA) within 7-10 days after AMI] and group B (subsequent PCI for non-IRA
      recommended only for those with evidence of ischemia). All of patients were given
      optimized medical therapy according to clinical guideline, and they were followed
      up for 24 months at regular intervals. Major adverse cardiovascular events (MACE)
      including recurrence of myocardial infarction and death due to cardiac ailments
      were recorded. Meanwhile, re-hospitalization from cardiac causes, recurrence of
      angina, heart failure, and re-PCI, number of stents, total hospital stay days,
      and total medical expenditure were recorded. RESULTS: A total of 428 patients
      accomplished the 24-month follow up. All the patients underwent PCI for non-IRA
      in group A (215 patients), while 62 patients in group B (213 patients) undergone
      PCI for myocardial ischemia, and 51 patients received non-IRA treatment. There
      was no significant difference in MACE incidence between group A and group B [8.4%
      (18/215) vs. 10.8% (23/213), chi2 = 0.727, P = 0.394]. The difference of death
      rate due to cardiac causes (5.1% vs. 6.6%), recurrence of myocardial infarction
      (4.2% vs. 6.6%), and heart failure (4.2% vs. 7.0%) were not significantly
      different between groups A and B (all P > 0.05). The rate of recurrence of angina
      (14.4 % vs. 32.9%), re-hospitalization from cardiac causes (14.4% vs. 33.8%), and
      re-treatment of implanting stents (12.6% vs. 29.1%) were significantly lower in
      group A than group B (all P < 0.01), and the rate of revascularization was
      significantly higher in group A than group B (10.7% vs. 5.2%, P < 0.05). The
      total number of stents (610 vs. 366), mean number of stents per patient (2.83 +/-
      0.91 vs. 1.72 +/- 0.91, t = 12.725, P = 0.000), and total cost per patient (kRMB:
      63.7 +/- 12.6 vs. 51.5 +/- 1 2.3, t = 10.107, P = 0.000) in group A were
      significantly higher than those in group B. Total hospital stay days in group A
      was significantly less than group B (days: 8.21 +/- 2.45 vs. 9.89 +/- .23, t =
      6.071, P = 0.000). Because non-IRA-vascular reconstruction rate was low in group
      B, the rate of using beta-blocker and anti-anginal agents during the 24-month
      follow up in group B was significantly higher than group A [59.2% (126/213) vs.
      47.0% (101/215), chi2 = 6.371, P = 0.012; 56.3% (112/213) vs. 17.6% (36/215),
      chi2 = 64.704, P = 0.000]. CONCLUSIONS: In patients with AMI and MVD undergone
      emergency PCI, staged PCI within 7-10 days for non-IRA cannot decrease the
      incidence of myocardial infarction and death due to cardiac causes, recurrence of
      angina and rehospitalization for cardiac causes was diminished, and it may
      increase the number of stents and medical cost significantly.

PMID- 25757965
TI  - [An analysis of relevant factors influencing the prognosis of post cardiac arrest
      syndrome].
AB  - OBJECTIVE: To investigate the relevant factors influencing the incidence and
      mortality of post cardiac arrest syndrome (PCAS), and to provide the basis of
      improvement of resuscitation rate. METHODS: A single center retrospective study
      of cardiopulmonary resuscitation (CPR) according to Utstein model was conducted.A
      clinical case report form was designed to collect clinical data. The clinical
      data of patients whose spontaneous circulation was restored (ROSC) > 24 hours in
      intensive care unit (ICU) of the First Hospital of Jilin University from January
      2008 to June 2014 were collected and analyzed. The relevant risk factors of the
      incidence and mortality rate of PCAS were screened and analyzed by multivariate
      logistic regression analysis. RESULTS: (1) Successful CPR was achieved in 93
      patients, of whom 83 patients were shown to have systemic inflammatory response
      syndrome (SIRS), and 75 patients suffered from PCAS (80.65%). Among them 49 died,
      and 18 patients who did not suffer from PCAS survived. (2) The age, gender,
      history of previous chronic disease, site of occurrence of cardiac arrest, type
      of rhythm when cardiac arrest occurred, and dosage of adrenaline showed no
      significant influence on the incidence of PCAS. The incidence of PCAS was
      elevated when defibrillation was done more than 3 times (chi2 = 10.806, P =
      0.001), SIRS occurred after ROSC (chi2 = 46.687, P < 0.001), interval between
      collapse and first defibrillation over 5 minutes (chi2 = 6.429, P = 0.011),
      interval between collapse and CPR longer than 5 minutes (chi2 = 4.638, P =
      0.031), interval between collapse and administration of first resuscitation
      medication > 5 minutes (chi2 = 4.190, P = 0.041), and ROSC time was longer than
      10 minutes (chi2 = 20.042, P < 0.001). Bivariate correlation showed that interval
      between collapse and CPR, interval between collapse and administration of first
      resuscitation medications, and ROSC time were all correlated (r1= 0.677, r2=
      0.481, r3= 0.617, all P < 0.001). (3) There were no significant relations between
      the prognosis of PCAS patients and times of defibrillation, the amount of
      adrenaline used, and interval between collapse and first defibrillation. The
      mortality rate of PCAS was relatively elevated when interval between collapse and
      CRP was longer than 5 minutes (chi2 = 10.792, P = 0.001), interval between
      collapse and administration of first resuscitation medications was longer than 5
      minutes (chi2 = 13.841, P < 0.001), ROSC time > 10 minutes (chi2 = 36.451, P <
      0.001), the number of dysfunction organ >= 4 (chi2 = 28.287, P < 0.001), arterial
      blood lactate levels > 2 mmol/L (chi2 = 28.926, P < 0.001), and acute physiology
      and chronic health evaluationII (APACHEII) score > 15 (chi2 = 33.558, P < 0.001).
      Multivariate logistic regression analysis showed that the risk factors affecting
      the prognosis were ROSC time [odds ratio (OR) after adjustment = 36.643, 95%
      confidence interval (95% CI) = 2.382-563.767, P = 0.010], the number of organs
      with dysfunction (OR = 9.010, 95% CI = 1.140-71.199, P = 0.037), and APACHEII
      score (OR = 10.001, 95%CI = 1.336-74.893, P = 0.025). CONCLUSIONS: ROSC time, the
      number of organs with dysfunction, and APACHEII score were independent predictors
      of PCAS prognosis. Efforts should be given to shorten the rescue time, to shorten
      the time for restoring the spontaneous circulation, to prevent and treat SIRS
      after ROSC, and to protect the function of organs, in order to improve the
      prognosis of patients with PCAS.

PMID- 25757966
TI  - [Impacts of sepsis-induced myocardial dysfunction on hemodynamics, organ function
      and prognosis in patients with septic shock].
AB  - OBJECTIVE: To investigate the impacts of sepsis-induced cardiac dysfunction on
      hemodynamics, organ function and prognosis in the patients with septic shock.
      METHODS: A prospective cohort study was conducted in 44 patients suffering from
      septic shock with the duration < 24 hours admitted to the Department of Critical
      Care Medicine of Peking University Third Hospital during June 2013 to June 2014.
      The patients were divided into two groups according to the left ventricular
      ejection fraction (LVEF) as recorded in echocardiogram at time of admission to
      the intensive care unit (ICU) as sepsis-induced myocardial dysfunction group
      (LVEF < 0.50, n = 11) and normal cardiac function group (LVEF >= 0.50, n = 33).
      The cardiac function evaluation and hemodynamics monitoring were performed with
      echocardiogram and pulse-induced contour cardiac output (PiCCO) on 1, 3, 7 days
      after the ICU admission. The plasma levels of the biomarkers of myocardial
      damage, troponin T (TnT) and N-terminal pro-brain natriuretic peptide (NT-proBNP)
      were measured, and the parameters representing organ function and the 28-day
      prognosis were collected as well. RESULTS: On the ICU admission, central venous
      pressure (CVP) and left ventricular end-diastolic diameter (LVEDD) were obviously
      lower in normal cardiac function group than those of myocardial dysfunction group
      [CVP (mmHg, 1 mmHg = 0.133 kPa): 10 +/- 4 vs. 14 +/- 6, P < 0.05; LVEDD (mm):
      45.0 +/- 5.3 vs. 51.8 +/- 7.1, P < 0.01], and there was no significant difference
      in other hemodynamic parameters between two groups. On the 3rd day, all the
      cardiac function and hemodynamic parameters showed no significant differences
      between the two groups. On the 7th day, the cardiac index (CI) and pulmonary
      vascular permeability index (PVPI) of normal cardiac function group were
      significantly higher than those of myocardial dysfunction group [CI (mL*s-1*m-2):
      63.3 +/- 13.3 vs. 48.3 +/- 10.0, P <0.05; PVPI: 1.5 (1.4, 1.9) vs. 1.1 (0.7,
      1.1), P < 0.01], and no significant difference was found in the other parameters.
      The plasma levels of TnT and NT-proBNP were found to have no difference at three
      time points between two groups. There was no difference in the number or the
      extent of organ dysfunction, including lung, kidney, liver and coagulation
      system, between the groups at the time of ICU admission. There was no obvious
      difference in the 28-day survival rate between the myocardial dysfunction group
      and normal cardiac function group [81.8% (9/11) vs. 72.7% (24/33), chi2 = 0.398,
      P = 0.528]. CONCLUSIONS: Sepsis-induced myocardial dysfunction is a reversible
      organ dysfunction. It can directly induce decreased left ventricular systolic
      function and enlargement of ventricle in patients with septic shock without
      reducing cardiac output or impairing the functions of other organs, or elevating
      the mortality rate.

PMID- 25757967
TI  - [Effect of pre-arrest and post-arrest mild hypothermia on myocardial function of
      ventricular fibrillation after restoration of spontaneous circulation in
      rabbits].
AB  - OBJECTIVE: To study the effect of pre-arrest and post-arrest mild hypothermia
      after restoration of spontaneous circulation (ROSC) on myocardial function,
      ultrastructure, apoptosis of myocardial cells in rabbits with ventricular
      fibrillation. METHODS: Sixty-two male New Zealand rabbits were randomly allocated
      into five groups: namely normothermic control group (NTC group, n = 10),
      hypothermia control group (HTC group, n = 10), normothermic resuscitation group
      (NTR group, n = 14), hypothermia pre-arrest group (HPRA group, n = 14), and
      hypothermia post-arrest group (HPOA group, n = 14). The normal temperature was
      controlled at (39.0 +/- 0.5) centigrade, and the hypothermia (33.5+/-0.5)
      centigrade. Ventricular fibrillation cardiac arrest (CA) was reproduced in
      rabbits by transcutaneous epicardium electrical stimulation. The parameters of
      hemodynamics were monitored dynamically for 4 hours in all the groups, including
      heart rate (HR), left ventricular end diastolic and systolic pressure
      (LVEDP/LVESP), maximal rate of increase/decrease in left ventricular pressure (+/
      dp/dt max), and mean arterial pressure (MAP). The body temperature of rabbits in
      hypothermia groups was maintained by surface cooling for 4 hours followed by
      rewarming. The survived rabbits were sacrificed at 48 hours after resuscitation,
      and myocardial apical tissue was harvested for observation of ultrastructure with
      electronic microscope, and to observe apoptosis by terminal deoxynucleotidyl
      transferase-mediated dUTP nick end labeling (TUNEL) staining. RESULTS: (1)
      Resuscitation investigation: there was no significant difference in rate of ROSC,
      time of CPR and energy of defibrillation among HPRA, HPOA, and NTR groups [rate
      of ROSC: 85.71%, 71.43%, 71.43%; time of CPR (seconds): 45.3 +/- 30.2, 61.2 +/-
      41.3, 82.3 +/- 63.8; energy of defibrillation (J): 14.3 +/- 8.9, 22.0 +/- 15.5,
      25.0 +/- 15.8, all P > 0.05]. (2) Hemodynamics: compared with normal temperature
      groups, animals in hypothermia groups exhibited lower levels of HR (all P <
      0.05). Compared with NTR group, HPRA group exhibited higher levels of LVESP
      (mmHg, 1 mmHg = 0.133 kPa) at 0.5, 1, 2 and 3 hours post ROSC (0.5 hour: 103.8 +/
      14.3 vs. 91.6 +/- 13.3, 1 hour: 107.2 +/- 14.1 vs. 82.7 +/- 8.5, 2 hours: 109.0
      +/- 16.9 vs. 88.8 +/- 12.9, 3 hours: 109.1 +/- 14.6 vs. 89.3 +/- 14.3, all P <
      0.05). Compared with NTR group and HPOA group, HPRA group exhibited lower levels
      of LVEDP (mmHg) at 0.5 hour post ROSC (3.70 +/- 0.85 vs. 7.61 +/- 2.73, 7.02 +/-
      3.12, both P < 0.05). Compared with NTR group, HPRA group exhibited lower levels
      of LVEDP at 1 hour post ROSC (4.34 +/- 1.44 vs. 6.99+/-1.96, P < 0.05). In HPRA
      group, the level of +dp/dt max (mmHg/s) was higher than that of NTR group and
      HPOA group at 1 hour and 2 hours post ROSC (1 hour: 2 759.5 +/- 321.6 vs. 2 123.0
      +/- 304.5, 2 283.7 +/- 234.2, 2 hours: 2 730.6+/-425.1 vs. 2 221.5 +/- 392.9, 2
      252.6 +/- 476.0, all P < 0.05). There were no significant differences in -dp/dt
      max and MAP levels among three CPR groups. (3) The survival rate at 48 hours post
      ROSC of NTR, HPRA and HPOA groups was 60%, 75%, and 100%, respectively. Compared
      with NTR group, higher survival rate was found in HPOA group at 48 hour post ROSC
      (P < 0.05). (4) Compared with NTR group, less damage to myocardial ultrastructure
      was found in HPRA and HPOA groups. Apoptosis index (AI) was lower in HPRA and
      HPOA groups than that in NTR group [(28.05 +/- 9.82) %, (26.39 +/- 8.98) % vs.
      (42.02 +/- 13.36) %, both P < 0.05]. CONCLUSIONS: Our study shows that mild
      hypothermia has no effect on ROSC rate. Pre-arrest hypothermia can ameliorate
      myocardial systolic function of rabbit in early stage after ROSC, and it has no
      negative influence on diastolic function. Post-arrest mild hypothermia produces
      no negative influence on myocardial function of rabbit, but it improves 48 hours
      survival rate in ROSC rabbits. Both pre-arrest and post-arrest mild hypothermia
      therapy can attenuate myocardial injury in CA model of rabbits by ameliorating
      mitochondrial injuries and suppressing apoptosis of myocardial cells.

PMID- 25757969
TI  - [The efficacy of hypertonic saline treatment in cardiopulmonary resuscitation in
      animal model with cardiac arrest: a Meta-analysis].
AB  - OBJECTIVE: To evaluate the efficacy of hypertonic saline (HS) treatment in
      cardiopulmonary resuscitation (CPR) in animal models of cardiac arrest (CA).
      METHODS: PubMed and EMBASE data were retrieved from January 1st, 1966 to
      September 30th, 2014, and Wanfang data and CNKI were searched from January 1st,
      1990 to September 30th, 2014 for randomized controlled trials (RCTs) regarding
      CPR intervention of CA animal models with HS. HS was intravenously infused at the
      initiation of CPR in HS group, without limiting its dosage or concentration. The
      same volume of normal saline (NS) was given in NS group. Meta-analysis concerning
      the rate of restoration of spontaneous circulation (ROSC), the serum sodium
      concentration before CA and during CPR, and related hemodynamic parameters,
      including mean arterial pressure (MAP) and coronary perfusion pressure (CPP) at
      the immediate beginning of CPR and 90 minutes after ROSC was conducted by RevMan
      5.3 software. RESULTS: A total of 8 RCTs were included. Meta-analysis showed that
      compared with NS group, the rate of ROSC [relative risk (RR) = 1.23, 95%
      confidence interval (95%CI) = 1.05-1.43, P = 0.010], serum sodium concentration
      during CPR [weight mean difference (WMD) = 17.44, 95%CI = 12.57-22.31, P < 0.01],
      and the level of MAP at 90 minutes after ROSC (WMD = 4.81, 95%CI = 1.58-8.03, P =
      0.003) were significantly improved in HS group. There was no significant
      statistic difference in other hemodynamic parameters, including serum sodium
      concentration before CA (WMD = 0.78, 95%CI = -0.26-1.82, P = 0.14), MAP (WMD =
      5.43, 95%CI = -0.74-11.59, P = 0.08) and CPP at the immediate beginning of CPR
      (WMD = 6.82, 95%CI = -5.54-19.19, P = 0.28), and CPP at 90 minutes after ROSC
      (WMD = -0.77, 95%CI = -10.33-8.80, P = 0.88) between two groups. It was showed by
      funnel chart that bias was not significant in the published articles.
      CONCLUSIONS: This systematic review indicates that HS infusion is followed by an
      improved ROSC rate, serum sodium concentration during CPR, and MAP at 90 minutes
      after ROSC in animal models of CA.

PMID- 25757968
TI  - [Effects of Shenfu injection on the expression of transcription factors T-bet /
      GATA-3 in pigs with post-resuscitation myocardial dysfunction].
AB  - OBJECTIVE: To examine whether Shenfu injection (SFI) reduces post-resuscitation
      myocardial dysfunction in a pig model by modulating expression imbalance of
      transcription factors of regulatory T cell, namely GATA-3 and T-bet. METHODS:
      Thirty pigs were randomly divided into sham group (n = 6) and cardiopulmonary
      resuscitation (CPR) group (n = 24) according to the random number table method,
      and the pigs in the CPR group were randomly subdivided into normal saline (NS)
      group, epinephrine (EP) group, and SFI group (n = 8 per group). After 8 minutes
      of untreated ventricular fibrillation (VF) followed by 2 minutes of CPR, animals
      in three groups respectively received central venous injection of either 20 mL
      SFI (1.0 mL/kg, SFI group), EP (0.02 mg/kg, EP group) or NS (NS group). Blood
      samples were obtained before VF and 0.5, 2, 6 hours after restoration of
      spontaneous circulation (ROSC), and the parameters of hemodynamics and oxygen
      metabolism were determined. Surviving pigs were sacrificed at 24 hours after
      ROSC, the pathological changes in myocardium were observed, the levels of
      interleukin-4 (IL-4), tumor necrosis factor-alpha (TNF-alpha) and gamma
      interferon (IFN-gamma) were measured by enzyme linked immunosorbent assay
      (ELISA), and expressions of protein and mRNA of GATA-3 and T-bet were determined
      by Western Blot and quantitative real-time polymerase chain reaction (RT-qPCR),
      respectively. RESULTS: Six pigs of three resuscitation groups were successfully
      resuscitated. The CPR time, number of defibrillation, defibrillation energy, and
      ROSC time were significantly decreased in the EP and SFI groups compared with
      those in the NS group. Compared with the sham group, the parameters of left
      ventricular systolic function and oxygen metabolism were significantly decreased,
      myofibril organelles were extensively damaged, and progressive and severe
      deterioration of the myocardium was found, and mitochondrial structure was not
      recognizable in the NS group; the level of IL-4 in myocardium were markedly
      decreased, while that of TNF-alpha, IFN-gamma and IFN-gamma/ IL-4 [reflecting
      helper T cell 1/2 (Th1/Th2)] were significantly increased. Protein and mRNA
      expressions of GATA-3 were markedly reduced in the myocardium of pigs in the NS
      group compared with that of the sham group at 24 hours after ROSC, while T-bet
      was significantly increased. Compared with the NS group, animals treated with SFI
      had minimal myocardial intracellular damage, with decreased heart rate (HR, bpm:
      90.33 +/- 3.79 vs. 106.83 +/- 5.36) and increased mean arterial pressure (MAP),
      cardiac output (CO), oxygen delivery (DO2), and oxygen consumption (VO2) at 6
      hours after ROSC [MAP (mmHg, 1 mmHg = 0.133 kPa): 107.67 +/- 1.96 vs. 86.83 +/-
      1.85, CO (L/min): 2.47 +/- 0.08 vs. 2.09 +/- 0.04, DO2 (mL/min): 364.31 +/- 4.21
      vs. 272.33 +/- 3.29, VO2(mL/min): 95.00+/-2.22 vs. 82.50 +/-2 .28, all P < 0.05].
      Compared with the NS groups at 24 hours after ROSC, level of IL-4 was markedly
      increased in myocardial cells (ng/L: 33.80 +/- 3.06 vs. 16.15 +/- 1.34, P <
      0.05), while the levels of TNF-alpha, IFN-gamma and IFN-gamma/IL-4 were lowered
      significantly [TNF-alpha (ng/L): 18.16 +/- 0.71 vs. 29.64 +/- 1.89, IFN-gamma
      (ng/L): 373.75 +/- 18.36 vs. 512.86 +/- 27.86, IFN-gamma/IL-4: 16.15 +/- 1.34 vs.
      33.80 +/- 3.06, all P < 0.05], and myocardial T-bet protein and mRNA expressions
      were reduced [T-bet protein (gray value): 0.41 +/- 0.07 vs. 0.59 +/- 0.11, T-bet
      mRNA (2(-DeltaDeltaCt)): 4.37 +/- 0.21 vs. 7.57 +/- 0.55, both P < 0.05],
      furthermore, myocardial GATA-3 protein and mRNA expressions were significantly up
      regulated in SFI group [GATA-3 protein (gray value): 0.25 +/- 0.07 vs. 0.16 +/-
      0.07, GATA-3 mRNA (2(-DeltaDeltaCt)): 0.63 +/- 0.07 vs. 0.34 +/- 0.05, both P <
      0.05]. The parameters in SFI group were significantly improved compared with
      those of the EP group. CONCLUSIONS: Myocardial immune dysfunction is induced by
      Th1/Th2 imbalance following myocardial injury subsequent to CPR in pigs. SFI can
      attenuate myocardial injury and regulate myocardial immune disorders, protect
      post-resuscitation myocardial injury by modulating expression imbalance of
      transcription factors GATA-3 and T-bet.

PMID- 25757970
TI  - [The role of pulse oximetry plethysmographic waveform monitoring as a marker of
      restoration of spontaneous circulation:a pilot study].
AB  - OBJECTIVE: To investigate the feasibility of using pulse oximetry
      plethysmographic waveform (POP) to identify the restoration of spontaneous
      circulation (ROSC) during cardiopulmonary resuscitation (CPR). METHODS: An
      observational research was conducted. A porcine model of ventricular fibrillation
      (VF) arrest was reproduced. After 3 minutes of untreated VF, animals received CPR
      according to the latest CPR guidelines, providing chest compressions to a depth
      of 5 cm with a rate of 105 compressions per minute and instantaneous mechanical
      ventilation. After 2 minutes of CPR, animals were defibrillated with 100 J
      biphasic, followed by continuous chest compressions. Data of hemodynamic
      parameters, partial pressure of end-tidal carbon dioxide (PETCO2) and POP were
      collected. The change in POP was observed, and the characteristics of changes of
      the waves were recorded during the peri-CPR period using the time and frequency
      domain methods. RESULTS: VF was successfully induced in 6 pigs, except 1 death in
      anesthesia induction period. (1) After VF, invasive blood pressure waveform and
      POP of the animals disappeared. PETCO2was (18.83 +/- 2.71) mmHg (1 mmHg=0.133
      kPa), and diastolic arterial pressure was (23.83 +/- 5.49) mmHg in compression
      stage. Animals attained ROSC within 1 minute after defibrillation, with
      PETCO2[(51.83 +/- 9.35) mmHg] and diastolic arterial pressure [(100.67 +/- 10.97)
      mmHg] elevated significantly compared with that of compression stage (t1 = 8.737,
      t2 = 25.860, both P = 0.000), with appearance of arterial blood pressure
      waveform.(2) Characteristic changes in POP were found in all experimental
      animals. During the stages of induced VF, compression, ROSC, and compression
      termination, POP showed characteristic waveform changes. POP showed disappearance
      of waveform, regular compression wave, fluctuation hybrid and stable pulse wave
      in time domain method; while in the frequency domain method waveform
      disappearance, single peak of compression, double or fusion peak and single peak
      of pulse were observed. CONCLUSIONS: Analysis of POP using time and frequency
      domain methods could not only quickly detect cardiac arrest, but also show a role
      as a feasible, non-invasive marker of ROSC during CPR.

PMID- 25757972
TI  - [The influence of serum magnesium level on the prognosis of critically ill
      patients].
AB  - OBJECTIVE: To investigate the incidence of hypomagnesemia and the effect of serum
      magnesium levels on the prognosis of critically ill patients in intensive care
      unit (ICU). METHODS: A single-center prospective observation was conducted. The
      adult patients admitted to ICU of Zhejiang Provincial People's Hospital from
      January 2012 to January 2014 were enrolled, and they were expected to stay in
      hospital for more than 48 hours. All the patients who had been diagnosed with
      hypomagnesemia before ICU admission, or those who had received magnesium
      supplement therapy were excluded. All patients were monitored for serum magnesium
      levels within 24 hours after ICU admission, and they were divided into three
      groups: normomagnesemic group (serum magnesium levels 0.7-1.2 mmol/L),
      hypomagnesemic group (serum magnesium levels < 0.7 mmol/L), and hypermagnesemic
      group (serum magnesium levels > 1.2 mmol/L). Various parameters were recorded for
      every patient, including general information, disease composition, laboratory
      indexes, duration of mechanical ventilation, ICU stay days and final outcome. The
      acute physiology and chronic health evaluation II (APACHEII) score and sequential
      organ failure assessment (SOFA) score during the first 24 hours after ICU
      admission were calculated. The risk factors for the death in critically ill
      patients were postulated by logistic regression analysis. RESULTS: A total of 374
      critically ill patients were enrolled, with 242 patients (64.71%) in
      normomagnesemic group, 102 (27.27%) in hypomagnesemic group, and 30 (8.02%) in
      hypermagnesemic group. As to the disease composition, although the patients in
      normomagnesemic group and hypomagnesemic group were mainly consisted of patients
      with nervous system diseases (33.06%, 31.37%) or pneumonia (25.62%, 25.49%), the
      proportion of patients with major abdominal and thoracic surgery (15.69% vs.
      5.78%, chi (2) = 8.837, P = 0.003) or severe sepsis (7.84% vs. 1.65%, chi (2) =
      9.935, P = 0.007) was significantly greater in the hypomagnesemic group compared
      with that of normomagnesemic group, and most hypermagnesemic patients were
      complicated by renal dysfunction in different degrees. Compared with the
      normomagnesemic group, the hypomagnesemic group was found to have higher SOFA
      scores (6.86+/-3.12 vs. 5.46+/-2.75, t = -2.930, P = 0.004), longer stay in ICU
      (days: 15.98+/-13.29 vs. 12.43+/-7.14, t = -2.318, P = 0.034) and higher
      mortality [54.90% (56/102) vs. 33.88% (82/242), chi (2) = 6.587, P = 0.010], but
      no statistically significant differences were found in gender composition, age,
      levels of other electrolytes (natrium, potassium, calcium, phosphorus), and
      APACHEII score. As shown by the result of the logistic regression analysis,
      APACHEII score [odds ratio (OR) = 1.129, 95% confidence interval (95%CI) = 1.064
      1.197, P = 0.000] and serum magnesium level (OR = 2.163, 95%CI = 1.015-4.610, P =
      0.046) were independent risk factors for death in critically ill patients.
      CONCLUSIONS: Serum magnesium levels are closely related to mortality rate in
      patients in ICU, so more attention should be paid to the occurrence of
      hypomagnesemia in critically ill patients.

PMID- 25757971
TI  - [Effect of anisodamine on myocardial connexin 43 expression in pig after
      resuscitation from cardiac arrest].
AB  - OBJECTIVE: To investigate the effect of anisodamine on the expression of connexin
      43 (Cx43) in swine ventricular myocardium after resuscitation from cardiac
      arrest. METHODS: The experiment was conducted on healthy pigs, and they were
      randomly divided into three groups, namely sham group, epinephrine group (control
      group) and anisodamine group (experimental group, animals were resuscitated
      combined with injection of 0.4 mg/kg of anisodamine), with 5 pigs in each group.
      Model of ventricular fibrillation was reproduced by alternating current
      challenge, and cardiopulmonary resuscitation (CPR) was performed 8 minutes after
      cardiac arrest. Left ventricular myocardium was harvested at 24 hours after
      restoration of spontaneous circulation. The expression and distribution of Cx43
      were observed by immunofluorescence, Cx43 mRNA expression was assessed with
      reverse transcription-polymerase chain reaction (RT-PCR), and the protein
      expressions of Cx43 and phosphorylation of Cx43 (p-Cx43) were analyzed by Western
      Blot. RESULTS: The positive expression of Cx43 in ventricular muscle was
      distributed uniformly, mostly at the end-to-end linkage of myocardial cells, with
      a few side-to-side linkage in sham group. The positive expression of Cx43 in
      control group was significantly weaker than that in the sham group, and the
      signal intensity was significantly declined (4.35+/-2.10 vs. 10.02+/-3.66, P <
      0.01). The positive expression of Cx43 at the end-to-end linkage and side-to-side
      linkage was irregular in experimental group, and the signal intensity was
      obviously higher than that in the control group (7.91+/-2.54 vs. 4.35+/-2.10, P <
      0.05), but it was significantly weaker than that in the sham group (7.91+/-2.54
      vs. 10.02+/-3.66, P < 0.05). For control group and experimental group, the Cx43
      mRNA and protein expressions were significantly lower than those of the sham
      group [Cx43 mRNA (A value): 0.32+/-0.05, 0.32+/-0.03 vs. 0.48+/-0.07; Cx43
      protein (A value): 0.43+/-0.03, 0.50+/-0.07 vs. 0.65+/-0.04, all P < 0.01], and
      there were no significant differences between experimental group and control
      group (all P > 0.05). The p-Cx43 protein expression of control group was
      significantly lower than that of the sham group (A value: 0.22+/-0.03 vs. 0.37+/
      0.06, P < 0.01), and it was significantly higher in the experiment group than
      that in the control group (A value: 0.29+/-0.07 vs. 0.22+/-0.03, P < 0.01), but
      there was no significant difference with the sham group (P > 0.05). No
      significant difference in p-Cx43/Cx43 was found among sham, control, and
      experiment groups (0.57+/-0.09, 0.51+/-0.05, 0.58+/-0.06, all P > 0.05).
      CONCLUSIONS: Anisodamine can improve the abnormal expression of Cx43 in
      ventricular muscle of pigs with cardiac arrest, which may be related to the
      protection effect of anisodamine on cardiac conduction.

PMID- 25757973
TI  - [Value of Micro RNA-499 in prediction of myocardial damage in sepsis].

PMID- 25757974
TI  - [Observation of effects of abdominal lifting-compression on lung tidal volume of
      patients with respiratory inhibition due to general anesthesia].

PMID- 25757975
TI  - [The effect of glucocorticoid on adrenaline receptors in the heart during
      cardiopulmonary resuscitation].

PMID- 25757976
TI  - [Effects of interrupted abdominal aorta counterpulsation cardiopulmonary
      resuscitation on cardiac arrest rabbit models during abdominal surgery].

PMID- 25757977
TI  - [The relationship between 5-hydroxy tryptamine levels and prognosis of patients
      in intensive care unit].

PMID- 25757978
TI  - [The application of disposable paste electrode on electrical cardioversion in
      patients suffering from emergency ventricular electrical storm].

PMID- 25757979
TI  - [Successful rescue of a patient with acute respiratory distress syndrome and
      septic shock with myocardial depression].

PMID- 25757980
TI  - [The protection function of extracorporeal membrane oxygenation for organ
      function donated by patients of cardiac death].

PMID- 25757981
TI  - [Advance of protective effect of intermedicine on organ function].

PMID- 25757982
TI  - UK NHS: less money (but more bangs per buck)?

PMID- 25757983
TI  - Influence of vascular risk factors on executive function among an age-homogeneous
      elderly cohort.
AB  - The pathogenesis of executive dysfunction in geriatric depression remains
      uncertain although causal bidirectional relationships with depression have been
      discussed. Previous studies have described a potential link with 'vascular
      depression'. In this study, we investigate the influence of vascular risk factors
      and magnetic resonance imaging markers of structural brain ageing, such as
      increasing deep white matter hyperintensities (DWMH), on executive function in an
      age-homogeneous population-based study cohort. A total of 606 participants of
      identical age (75.8 years; standard deviation 0.45 years) took part in the
      baseline investigation of the Vienna Transdanube Ageing (VITA) study. Each
      participant underwent a full psychometric examination with standardised
      neuroimaging and clinical chemistry investigations. Participants were re-examined
      with the same protocol after exactly 30 and 60 months. Data refer to the
      individuals who completed the examination at baseline. In the ordinal logistic
      regression, fewer years of education (P < 0.0001), Trail Making Test-A (P <
      0.0001), high homocysteine (P = 0.001), and depression (P < 0.0001) were
      significantly associated with Trail Making Test-B (TMT-B) values. A significant
      influence of other vascular risk factors, such as lipids, diabetes, and smoking,
      on executive dysfunction was not observed. A comparison of both lacunes and DWMH
      with respect to the TMT-B results showed no significant correlation. Our data do
      not support the notion that vascular pathogenesis might underlie executive
      dysfunction.

PMID- 25757984
TI  - Introduction to the Special Issue: Halophytes in a changing world.
AB  - Climate change will bring about rising sea levels and increasing drought, both of
      which will contribute to increasing salinization in many regions of the world.
      There will be consequent effects on our crops, which cannot withstand significant
      salinization. This Special Issue looks at the roles that can be played by
      halophytes, extremophiles that do tolerate salinities toxic to most plants. In an
      ecological context, papers deal with the conservation of a rare species, the
      effects of rising concentrations of CO2 and flooding on coastal vegetation, and
      the consequences of tree planting in inland plains for salinization.
      Physiological studies deal with the different effects of chlorides and sulfates
      on the growth of halophytes, the ability of some parasitic plants to develop
      succulence when growing on halophytic hosts and the interesting finding that
      halophytes growing in their natural habitat do not show signs of oxidative
      stress. Nevertheless, spraying with ascorbic acid can enhance ascorbic acid
      dependent antioxidant enzymes and growth in a species of Limonium. Enzymes
      preventing oxidative stress are expressed constitutively as is the case with the
      vacuolar H-ATPase, a key enzyme in ion compartmentation. A comparison of salt
      excreting and non-excreting grasses showed the former to have higher shoot to
      root Na(+) ratios than the latter. A particularly tolerant turf grass is
      described, as is the significance of its ability to secrete ions. A study of 38
      species showed the importance of the interaction of a low osmotic potential and
      cell wall properties in maintaining growth. From an applied point of view, the
      importance of identifying genotypes and selecting those best suited for the
      product required, optimizing the conditions necessary for germination and
      maximizing yield are described. The consequence of selection for agronomic traits
      on salt tolerance is evaluated, as is the use of halophytes as green manures.
      Halophytes are remarkable plants: they are rare in relation to the total number
      of flowering plants and they tolerate salinities that most species cannot. It is
      clear from the papers published in this Special Issue that research into
      halophytes has a distinct place in aiding our understanding of salt tolerance in
      plants, an understanding that is likely to be of importance as climate change and
      population growth combine to challenge our ability to feed the human population
      of the world. 

PMID- 25757985
TI  - Dependence of distance distributions derived from double electron-electron
      resonance pulsed EPR spectroscopy on pulse-sequence time.
AB  - Pulsed double electron-electron resonance (DEER) provides pairwise P(r) distance
      distributions in doubly spin labeled proteins. We report that in protonated
      proteins, P(r) is dependent on the length of the second echo period T owing to
      local environmental effects on the spin-label phase memory relaxation time Tm .
      For the protein ABD, this effect results in a 1.4 A increase in the P(r) maximum
      from T=6 to 20 MUs. Protein A has a bimodal P(r) distribution, and the relative
      height of the shorter distance peak at T=10 MUs, the shortest value required to
      obtain a reliable P(r), is reduced by 40 % relative to that found by
      extrapolation to T=0. Our results indicate that data at a series of T values are
      essential for quantitative interpretation of DEER to determine the extent of the
      T dependence and to extrapolate the results to T=0. Complete deuteration (99 %)
      of the protein was accompanied by a significant increase in Tm and effectively
      abolished the P(r) dependence on T. 

PMID- 25757986
TI  - Ten years' experience in endovascular repair of popliteal artery aneurysm using
      the Viabahn endoprosthesis: a report from two Italian vascular centers.
AB  - BACKGROUND: Although rare, popliteal artery aneurysms (PAAs) are the most
      commonly observed peripheral arterial aneurysms. Surgical repair is considered
      the gold standard, even if with debated results. The aim of our study is to
      evaluate the outcome of endovascular treatment of PAAs using the Viabahn
      peripheral endograft (W. L. Gore and Associates, Inc., Flagstaff, AZ) in 2 high
      volume Italian centers. METHODS: All consecutive PAA patients treated by
      endovascular procedures between January 2004 and December 2013 were
      retrospectively reviewed. True atherosclerotic aneurysms, symptomatic and
      asymptomatic, were included in the analysis. All patients were treated by high
      skilled vascular surgeons. The outcome measures were graft thrombosis,
      reintervention rate, and limb salvage at early and long-term follow-up. RESULTS:
      Fifty-three PAAs were treated. Patients were more frequently male (98.1%) with a
      mean age of 73.6 +/- 7.8 years. Twelve patients (22.6%) were symptomatic and in 8
      of them a local fibrinolysis was required before definitive surgery. Mean PAA
      diameter was 30.9 +/- 10.9 mm (range 17-60). Fifty-two patients (98.1%) had at
      least 1 patent runoff vessel. Technical success was achieved in all patients.
      Overall, 80 stent grafts were deployed and in 21 patients (39.6%) more than 1
      stent graft was deployed. In-hospital mortality rate and 30-day reinterventions
      were null. At a mean follow-up of 37.4 +/- 29.3 months, primary patency,
      secondary patency, and limb salvage were respectively 73.6%, 92.4%, and 100%.
      CONCLUSION: In our limited, retrospective experience, the endovascular treatment
      of PAA by Viabahn stent graft allowed satisfactory technical and clinical results
      even at long-term follow-up.

PMID- 25757987
TI  - The role of asymmetric and symmetric dimethylarginine in acute deep vein
      thrombosis.
AB  - BACKGROUND: In this study, we aimed to determine the importance of asymmetric
      dimethylarginine (ADMA), symmetric dimethyl arginine (SDMA), and l-arginine
      levels which are influenced by the endothelial dysfunction in acute deep vein
      thrombosis (DVT), and compare their pretreatment and post-treatment levels.
      METHODS: A total of 34 cases (19 men and 15 women, age range 42 +/- 14 years)
      diagnosed with acute DVT and 34 control subjects (22 men and 12 women, age range
      45 +/- 11 years) without any vascular disorders were included in the study. The
      patients were administered low-molecular-weight heparin subcutaneously. Blood
      samples were obtained to measure ADMA, SDMA, and arginine levels before treatment
      and during the treatment (on 10th day). ADMA, SDMA, and l-arginine levels were
      measured using high performance liquid chromatography method. RESULTS: The ADMA
      and SDMA levels were significantly higher in acute DVT patients when compared
      with the controls (P = 0.001). Post-treatment decrease of ADMA and SDMA levels
      when compared with the pretreatment levels were found as statistically
      significant (P = 0.001). Increase in l-arginine levels were not found significant
      when compared with the control group (P = 0.12) or post-treatment levels (P =
      0.16). CONCLUSIONS: We concluded that ADMA and SDMA levels can be used as
      parameters in clinical follow-up for determining the efficacy of treatment in
      acute DVT patients, and further studies are needed to further clarify the
      subject.

PMID- 25757988
TI  - Comparison of clinical outcomes of endovascular versus open revascularization for
      chronic mesenteric ischemia: a meta-analysis.
AB  - BACKGROUND: The purpose of this study is to compare the clinical outcomes of
      endovascular versus open revascularization for chronic mesenteric ischemia (CMI).
      METHODS: Published studies that investigated endovascular versus open
      revascularization for CMI were identified, and meta-analysis was used for
      statistical analysis. RESULTS: Eight studies were analyzed by meta-analysis
      method, cumulative 569 cases were included. Endovascular treatments were
      performed in 209 cases, and open repairs were performed in 360 cases. Meta
      analysis showed that there was no difference in 30-day mortality and 3-year
      cumulative survival rate between the endovascular group and the open group (P =
      0.55 and P = 0.56); compared with the open revascularization group, the
      endovascular revascularization group resulted in significantly lower rate of in
      hospital complication (P = 0.002), while recurrence rate within 3 years after
      revascularization was significantly greater in the endovascular revascularization
      group (P < 0.00001). CONCLUSION: Endovascular treatment offers a benefit of lower
      in-hospital complication rate, but a greater recurrence rate within 3 years after
      revascularization compared with the open revascularization, and both groups have
      similar 30-day mortality and 3-year cumulative survival rate.

PMID- 25757989
TI  - Aortoiliac elongation after endovascular aortic aneurysm repair.
AB  - BACKGROUND: Aortoiliac elongation after endovascular aortic aneurysm repair
      (EVAR) is not well studied. We sought to assess the long-term morphologic changes
      after EVAR and identify potentially modifiable factors associated with such a
      change. METHODS: An institutional review board-approved retrospective review was
      conducted for 88 consecutive patients who underwent EVAR at a single academic
      center from 2003 to 2007 and who also had at least 2 follow-up computed
      tomography angiograms (CTAs) available for review up to 5 years after surgery.
      Standardized centerline aortic lengths and diameters were obtained on Aquarius
      iNtuition 3D workstation (TeraRecon Inc., San Mateo, CA) on postoperative and all
      available follow-up CTAs. Relationships to aortic elongation were determined
      using Wilcoxon rank-sum test or linear regression (Stata version 12.1, College
      Station, TX). Changes in length over time were determined by mixed-effects
      analysis (SAS version 9.3, Cary, NC). RESULTS: The study cohort was composed of
      mostly men (88%), with a mean age of (76 +/- 8) and a mean follow-up of 3.2 years
      (range, 0.4-7.5 years). Fifty-seven percent of patients (n = 50) had devices with
      suprarenal fixation and 43% (n = 38) had no suprarenal fixation. Significant
      lengthening was observed over the study period in the aortoiliac segments, but
      not in the iliofemoral segments. Aortoiliac elongation over time was not
      associated with sex (P = 0.3), hypertension (P = 0.7), coronary artery disease (P
      = 0.3), diabetes (P = 0.3), or tobacco use (P = 0.4), but was associated with the
      use of statins (P = 0.03) and the presence of chronic obstructive pulmonary
      disease (P = 0.02). Significant aortic lengthening was associated with increased
      type I endoleaks (P = 0.03) and reinterventions (P = 0.03). Over the study
      period, 4 different devices were used; Zenith (Cook Medical Inc., Bloomington,
      IN), Talent (Medtronic, Minneapolis, MN), Aneuryx (Medtronic), and Excluder (W.
      L. Gore and Associates Inc., Flagstaff, AZ). After adjusting for differences in
      proximal landing zone, significant differences in aortic lengthening over time
      were observed by device type (P = 0.02). CONCLUSIONS: Significant aortoiliac
      elongation was observed after EVAR. Such morphologic changes may impact long-term
      durability of EVAR, warranting further investigation into factors associated with
      these morphologic changes.

PMID- 25757990
TI  - A multidisciplinary approach for abdominal venous involvement in oncologic
      resections.
AB  - BACKGROUND: An aggressive surgical approach to locally advanced malignancy is
      being increasingly used in the absence of distant metastatic disease. This
      includes resection and reconstruction of major venous structures. We investigated
      the results of using a multidisciplinary surgical approach in these instances.
      METHODS: The study data were obtained from a university-affiliated hospital from
      January 1, 2006, to December 31, 2012. All patients who underwent an oncologic
      resection using a multidisciplinary approach with vascular surgery consultation
      were included in the analysis. Primary outcomes analyzed included rate of margin
      positivity, postoperative venous patency, and survival. Secondary outcome
      measures included operative time, estimated blood loss, and length of hospital
      stay. RESULTS: A total of 23 patients met criteria for study. Venous involvement
      included the portal and/or superior mesenteric vein and inferior vena cava in 14
      and 9 patients, respectively. Nine patients had clear vascular involvement before
      surgery and received preoperative consultation. Overall margins were positive in
      56.5%, whereas the rate of vascular margin positivity was 30.4%. The
      postoperative venous patency rate was 65.0%. There were no perioperative
      mortalities, and median survival was 10 months (range, 4-80). CONCLUSIONS: Major
      venous resections and reconstructions in oncologic surgery are safe but
      associated with a high rate of positive margins. Future efforts should focus on
      identifying patients in the preoperative phase to provide opportunity for optimal
      multidisciplinary planning.

PMID- 25757991
TI  - Racial disparities in outcomes of endovascular procedures for peripheral arterial
      disease: an evaluation of California hospitals, 2005-2009.
AB  - BACKGROUND: Racial/ethnic disparities in treatment outcomes of peripheral
      arterial disease (PAD) are well documented. Compared with non-Hispanic (NH)
      whites, blacks and Hispanics are more likely to undergo amputation and less
      likely to undergo bypass surgery for limb salvage. Endovascular procedures are
      being increasingly performed as first line of therapy for PAD. In this study, we
      examined the outcomes of endovascular PAD treatments based on race/ethnicity in a
      contemporary large population-based study. METHODS: We used Patient Discharge
      Data from California's Office of Statewide Health Planning and Development to
      identify all patients over the age of 35 who underwent a lower extremity arterial
      intervention from 2005 to 2009. A look-back period of 5 years was used to exclude
      all patients with prior lower extremity arterial revascularization procedures or
      major amputation. Cox proportional hazards regression was used to compare
      amputation-free survival and time to death within 365 days. Logistic regression
      was used for comparison of 1-month myocardial infarction, 1-month major
      amputation, 1-month all-cause mortality, 12-month major amputation, 12-month
      reintervention, and 12-month all-cause mortality rates among NH white, black, and
      Hispanic patients. These analyses were adjusted for age, gender, insurance
      status, severity of PAD, comorbidities, history of coronary artery angioplasty or
      bypass surgery, or history of carotid endarterectomy. RESULTS: Between 2005 and
      2009, a total of 41,507 individuals underwent PAD interventions, 25,635 (61.7%)
      of whom underwent endovascular procedures. There were 17,433 (68%) NH whites,
      4,417 (17.2%) Hispanics, 1,979 (7.7%) blacks, 1,163 (4.5%) Asian/Native
      Hawaiians, and 643 (2.5%) others in this group. There was a statistically
      significant difference in the amputation-free survival within 365 days among the
      NH white, Hispanic, and black groups (P < 0.0001); the hazard ratio for
      amputation within 365 days was 1.69 in Hispanics (95% confidence interval [CI]
      1.51-1.90, P < 0.0001) and 1.68 in blacks (95% CI 1.44-1.96, P < 0.001) compared
      with NH whites following endovascular procedures after adjusting for age, gender,
      insurance status, comorbidities, severity of PAD, history of coronary artery
      angioplasty or bypass surgery, or history of carotid endarterectomy. After
      adjusting for the aforementioned confounders, the first reintervention within 12
      months was also significantly associated with race/ethnicity (P = 0.002). Odds
      ratio for reintervention was 1.17 in blacks (95% CI 1.06-1.30, P = 0.002) and
      1.084 in Hispanics (95% CI 1.00-1.16, P = 0.04) compared with NH whites.
      CONCLUSIONS: In this contemporary large population-based study, we demonstrated
      that even among matched cohorts Hispanics and blacks have worse amputation-free
      survival than NH whites following endovascular therapy. Our study also found that
      Hispanics and blacks are more likely to undergo lower extremity arterial
      reinterventions than NH whites. Further research is crucial in understanding if
      higher reintervention rates in Hispanics and blacks are because of more severe
      disease and/or poor access to proper follow-up care and optimal medical
      management.

PMID- 25757993
TI  - Open repair and venous inflow plication of the arteriovenous fistula is effective
      in treating vascular steal syndrome.
AB  - BACKGROUND: Vascular steal syndrome related to a dialysis arteriovenous fistula
      (AVF) can lead to symptoms of distal ischemia, limb loss, digit ulceration, and
      gangrene. Several complex procedures have been used to augment and restore distal
      limb perfusion while maintaining a functional AVF. We reviewed our experience in
      treating AVF-related vascular steal syndrome by simple plication of the initial
      AVF inflow segment. METHODS: Clinical data of 26 patients (15 men; mean age, 58
      years; range, 26-80) with vascular steal syndrome related to their AVF underwent
      plication during a 36-month period. There were 18 brachial-cephalic AVFs and 8
      brachial-basilic AVFs with vein transposition. Relevant clinical variables,
      imaging studies, and treatment variables were analyzed. RESULTS: Eighty-four
      percent of patients had hypertension, 62% were diabetics, and 15% had a previous
      limb or digit amputated. Hand pain, skin ulceration, or gangrene was present in
      96%, 15%, and 12% of patients, respectively; 19% of patients had more than one
      symptom. Twelve (46%) patients had an aortic arch and upper extremity
      arteriogram, of which 67% showed evidence of arterial disease. One patient
      required percutaneous balloon-expandable stent treatment of a proximal left
      subclavian artery stenosis to improve flow. Duplex-derived volume flow
      measurements of the AVF were obtained with an average flow of 1.95 +/- 0.83
      L/min. Open repair and venous inflow plication was performed in all 26 patients.
      Average flow reduction in patients with preoperative and postoperative flow
      measurements was 0.6 +/- 0.5 L/min (P < 0.05). There was a 12% revision rate
      within 3 months. Symptom resolution was achieved in 92% of patients while
      maintaining a functioning access out to 1 year. Two remaining patients who did
      not improve and proceeded to ligation of the AVF. CONCLUSIONS: Surgical plication
      of the initial AVF inflow segment offers a simple solution to preserve the
      dialysis access and resolve symptoms related to vascular steal associated with
      high volume flow through the AVF.

PMID- 25757992
TI  - Cohort comparison of thoracic endovascular aortic repair with open thoracic
      aortic repair using modern end-organ preservation strategies.
AB  - BACKGROUND: Pivotal trials showed that thoracic endovascular aortic repair
      (TEVAR) has improved outcomes compared with open surgery for treating descending
      thoracic aortic aneurysms. However, those trials included historical open
      controls in which modern end-organ preservation strategies were not routinely
      employed. To create a more level assessment, we compared our outcomes of elective
      TEVAR with modern open thoracic aortic repair (OTAR) controls. METHODS: A
      retrospective review of thoracic aortic aneurysm patients undergoing TEVAR was
      compared with a contemporaneous cohort of OTAR patients. Partial bypass or
      hypothermic circulatory arrest was used in all OTAR patients. Cerebrospinal fluid
      drain placement was attempted in all patients. Preoperative characteristics,
      operative variables, and outcomes were recorded, and the Kaplan-Meier method was
      used for survival estimates. RESULTS: The main outcome was mortality. Secondary
      outcomes included postoperative spinal cord ischemia (SCI) or stroke, and any
      persistent neurologic deficit 30 days following the operation. During the study
      period, 62 patients underwent TEVAR and 56 underwent OTAR with median follow-up
      of 23.7 months and 36.4 months, respectively. No difference existed between the
      TEVAR and OTAR with respect to overall neurologic complications (8.1% vs. 12.5%,
      P = 0.55) as well as any residual neurologic deficit at 30 days (0% vs. 5.4%, P =
      0.10). TEVAR patients had fewer complications including pneumonia (P = 0.02),
      rebleeding (P = 0.02), and acute kidney injury (P = 0.001). There was no
      difference in 30-day mortality (1.6% vs. 8.9%, P = 0.10), 1-year mortality (12.2%
      vs. 14%, P = 0.80), or 5-year mortality (53.9% vs. 44%, P = 0.48) between TEVAR
      and OTAR, respectively. CONCLUSIONS: TEVAR continues to show improved
      perioperative outcomes with a trend toward decreased 30-day mortality and fewer
      major adverse events compared with OTAR. However, with the routine use of end
      organ preservation strategies during OTAR, neurologic deficits, particularly SCI,
      can be safely reduced to comparable levels with those of TEVAR and 1-year all
      cause mortality rates are similar between the groups. These OTAR results may
      serve as a benchmark as TEVAR is increasingly applied for other aortic
      pathologies, such as chronic dissection, wherein long-term efficacy is not
      proven.

PMID- 25757994
TI  - Mid- and long-term outcome of patients with permanent inferior vena cava filters:
      a single center review.
AB  - BACKGROUND: Inferior vena cava (IVC) filters are used to prevent pulmonary
      embolism (PE), especially in patients with active contraindication to systemic
      anticoagulation. The aim of this study is to examine the outcomes of patients who
      received permanent IVC filters at our institution. METHODS: This is a single
      center retrospective observational study with review of a prospectively collected
      database for patients who had permanent IVC filters. Patient demographics,
      indications of filter placement, postprocedure clinical outcome and
      complications, as well as use of anticoagulant therapy were documented. Chi
      squared test was used to test for statistically significant differences (IBM SPSS
      version 21; IBM Corp., Armonk, NY), while survival was calculated using Kaplan
      Meier survival curves analysis. RESULTS: Between February 1998 and December 2013,
      a total of 109 patients with a median age of 65 (47 men, range 19-97) years had
      IVC filters inserted at our institution. All of them had documented venous
      thromboembolism (VTE) before filter placement: 99 (90.8%) had lower extremity
      deep vein thrombosis (DVT) (including 34 iliac, 65 infrainguinal), 9 (8.3%) had
      massive PE without evidence of lower limb DVT, and 1 (0.9%) had isolated IVC
      thrombosis. Forty-seven (43.1%) patients had PE before filter insertion. There
      were 2 serious procedure-related complications: one access site thrombosis and
      one right ventricular perforation. With a mean follow-up of 36 +/- 33 months, no
      patient had further symptomatic PE or paradoxical embolism. There were a total of
      54 (49.5%) deaths, with a 30-day mortality of 8.3%; none of them was device or
      procedure related. Among the 92 patients followed up, 27 (29.3%) had further VTE
      either DVT in the index or the contralateral lower limb (20 patients, 21.7%), or
      thrombus inside the filter or the IVC (14 patients, 15.2%). Forty-one (44.6%)
      patients reported post-thrombotic syndrome (PTS) symptoms. Anticoagulant therapy
      was given to 39 (42.4%) and 55 (59.8%) patients in the periprocedural period and
      at any time during the study period, respectively. It did not reduce the rate of
      postfilter VTE or PTS in both instances. None of the filters in this series was
      retrieved. CONCLUSIONS: This observational study showed that IVC filters were
      effective in the prevention of PE, although symptomatic postfilter VTE and PTS
      were common, leading to significant morbidity. Patients who received permanent
      filters have high mortality on follow-up; however, none were procedure or device
      related.

PMID- 25757995
TI  - Differences in housing, health, and well-being among HIV-positive women living in
      poverty.
AB  - The social context of living in poverty has a direct and indirect impact on a
      woman's health and well-being. This cross-sectional study investigates the
      relationship between housing and adherence to treatment, emotional wellness,
      environmental safety, physical health status, and risk behaviors among HIV
      positive women receiving services from an AIDS service organization in the mid
      South. Significant differences were found between stably housed and unstably
      housed women on the dependent outcome variables. Results suggest that housing
      services for HIV-positive women may be an effective way to increase their health
      and well-being as well as prevent transmission to others. 

PMID- 25757996
TI  - Compensatory motor network connectivity is associated with motor sequence
      learning after subcortical stroke.
AB  - Following stroke, functional networks reorganize and the brain demonstrates
      widespread alterations in cortical activity. Implicit motor learning is preserved
      after stroke. However the manner in which brain reorganization occurs, and how it
      supports behavior within the damaged brain remains unclear. In this functional
      magnetic resonance imaging (fMRI) study, we evaluated whole brain patterns of
      functional connectivity during the performance of an implicit tracking task at
      baseline and retention, following 5 days of practice. Following motor practice, a
      significant difference in connectivity within a motor network, consisting of
      bihemispheric activation of the sensory and motor cortices, parietal lobules,
      cerebellar and occipital lobules, was observed at retention. Healthy subjects
      demonstrated greater activity within this motor network during sequence learning
      compared to random practice. The stroke group did not show the same level of
      functional network integration, presumably due to the heterogeneity of functional
      reorganization following stroke. In a secondary analysis, a binary mask of the
      functional network activated from the aforementioned whole brain analyses was
      created to assess within-network connectivity, decreasing the spatial
      distribution and large variability of activation that exists within the lesioned
      brain. The stroke group demonstrated reduced clusters of connectivity within the
      masked brain regions as compared to the whole brain approach. Connectivity within
      this smaller motor network correlated with repeated sequence performance on the
      retention test. Increased functional integration within the motor network may be
      an important neurophysiological predictor of motor learning-related change in
      individuals with stroke. 

PMID- 25757998
TI  - Challenges in the synthetic routes to Mn(BH4)2: insight into intermediate
      compounds.
AB  - We have studied the reaction of MnCl2 with MBH4 (M = Li(+), Na(+), K(+)) in Et2O.
      Crystal structures of two new intermediates, named [{M(Et2O)2}Mn2(BH4)5] (M =
      Li(+), Na(+)), were elucidated by X-ray diffraction. Mn(BH4)2 in a mixture with
      LiBH4 or NaBH4 forms upon the solvent removal in a vacuum. [{M(Et2O)2}Mn2(BH4)5]
      contains 2D layers formed by Mn and BH4 groups, linked through the alkali metal
      atoms coordinated to Et2O. The loss of the solvent molecules leads to the
      segregation of the partially amorphous or nanocrystalline LiBH4/NaBH4 and a
      creation of the 3D framework of the crystalline Mn(BH4)2. While using LiBH4 led
      to Mn(BH4)2 contaminated with LiCl, presumably due to an efficient trapping of
      the latter salt by the [Mn(BH4)2-Et2O] system, the reaction with NaBH4 produced
      chlorine-free Mn(BH4)2 accompanied with NaBH4. Using KBH4 led to the formation of
      K2Mn(BH4)4 as a second phase. Two pyridine-containing solvomorphs,
      [Mn(py)3(BH4)2] and [Mn(py)4(BH4)2].2py, were isolated in pure form. However,
      Mn(BH4)2 partly decomposes upon removal of pyridine molecules. 

PMID- 25757997
TI  - Long-term follow-up of patients with phenylketonuria treated with
      tetrahydrobiopterin: a seven years experience.
AB  - BACKGROUND: Phenylketonuria (PKU) is an autosomal recessive disorder caused by
      the deficiency of phenylalanine hydroxylase that catalyzes the conversion of
      phenylalanine to tyrosine, using tetrahydrobiopterin (BH4) as coenzyme. Besides
      dietary phenylalanine restriction, new therapeutic options are emerging, such as
      the treatment with BH4 in subgroups of PKU patients responding to a loading test
      with BH4. METHODS: A no-profit open-label interventional trial with long-term
      oral BH4 therapy, sponsored by the Italian Medicines Agency (AIFA), was performed
      in a group of 17 PKU patients resulted as BH4 responders among 46 subjects
      analyzed for BH4-responsiveness (prot. FARM5MATC7). We report on efficacy and
      safety data of BH4 therapy and analyze factors predicting BH4-responsiveness and
      long-term response to BH4. A BH4-withdrawal test was used as a proof of the
      efficacy of long-term therapy with BH4. RESULTS: Forty-four percent of the
      patients responded to the 48 h-long loading test with BH4. All the phenotypic
      classes were represented. Genotype was the best predictor of responsiveness,
      along with lower phenylalanine levels at diagnosis, higher tolerance and lower
      phenylalanine/tyrosine ratio before the test. In BH4 responder patients, long
      term BH4 therapy resulted safe and effective in increasing tolerance while
      maintaining a good metabolic control. The BH4 withdrawal test, performed in a
      subset of patients, showed that improved tolerance was directly dependent on BH4
      assumption. Tolerance to phenylalanine was re-evaluated in 43.5% of patients and
      was longitudinally analyzed in 5 patients. CONCLUSIONS: Long-term treatment with
      BH4 is safe and effective in increasing tolerance to phenylalanine. There is real
      need to assess the actual tolerance to phenylalanine in PKU patients to
      ameliorate quality of life, improve nutritional status, avoiding unnecessarily
      restricted diets, and interpret the effects of new therapies for PKU.

PMID- 25757999
TI  - Do mandatory nasal interventions after epistaxis just delay discharge?--Our
      experience in 90 adults.

PMID- 25758000
TI  - Isolated sulfite oxidase deficiency.
AB  - BACKGROUND: Sulfite oxidase deficiency is an uncommon metabolic disease. Only few
      cases of its isolated form have been reported in the literature. CASE
      PRESENTATION: We report a case of severe neonatal onset. A newborn baby of 41
      weeks gestational age, weighted at birth of 3240 grams and had an Apgar score of
      6-10-10. Fifty-three hours after being born, the baby started with seizures that
      were refractory to antiepileptic treatment. Brain function was monitored using a
      EEG. Laboratory and imaging tests were performed. All of them were consistent
      with sulfite oxidase deficiency. The diagnosis was confirmed by genetic testing.
      CONCLUSIONS: We highlight the importance of this disease as part of the
      differential diagnosis of seizures during the neonatal period, as well as the
      importance of the therapeutic support based on dietary restrictions. It's also
      remarkable the possibility of prenatal diagnosis by quantifying enzyme activity
      and it's also possible carrying out DNA mutational analysis.

PMID- 25758001
TI  - Bilateral acute neonatal suppurative parotitis: A rare finding in neonatal age.
AB  - Acute suppurative parotitis is a rare entity in neonates. Bilateral involvement
      is extremely rare. Low birth weight, prematurity, gavage feeding, dehydration,
      sepsis are all known risk factors. Staphylococcus aureus is the most common
      organism, other organisms responsible for parotitis are streptococcus, E. coli,
      pseudomonas and klebsiella. We report a neonate suffering from bilateral acute
      suppurative parotitis with an unusual causative association. CPAP and its
      association for acute suppurative parotitis has been proposed.

PMID- 25758002
TI  - Diagnosis and management of fetal ductus arteriosus constriction-closure.
AB  - Pathognomonic features of in utero premature restriction/closure of the ductus
      arteriosus (DA) are increased right ventricular afterload, impaired right
      ventricular function, and consequently tricuspid regurgitation and right heart
      dilation. The most common reason for constriction-closure of DA is maternal
      administration of non-steroidal anti-inflammatory drugs (NSAIDs) during the 3rd
      trimester of gestation. The idiopathic form is a rare event and, maybe, an
      underestimated abnormality that, if it is not promptly recognized, may result in
      severe fetal-neonatal compromise. We describe a case of a 38-year-old woman
      presenting at 34+0 weeks of gestation with a normally grown male fetus whose
      fetal echocardiography had shown right ventricular hypertrophy, a tortuous S
      shaped DA and a significant pulmonary hyperflow. All signs were consistent of an
      idiopathic severe constriction of DA with a significant fetal cardiac
      involvement. The patient was admitted to a tertiary care center equipped with
      Neonatal Intensive Care Unit (NICU), and delivered by cesarean section at 34+4
      weeks with a good maternal and neonatal outcome. Based on our experience and a
      review of the Literature we propose a management algorithm to use when dealing
      with preterm or early term pregnancy complicated by this fetal hemodynamic
      malfunction.

PMID- 25758003
TI  - Prolonged phototherapy needed for a neonate with four mutations in genes involved
      in bilirubin production and metabolism.
AB  - We cared for a neonate with hyperbilirubinemia requiring phototherapy during the
      birth-hospitalization, at home, and during two subsequent hospital readmissions.
      Abnormal red blood cell forms including elliptocytes were seen on his blood film
      but this failed to explain, to our satisfaction, why his jaundice required such
      prolonged treatment. Next-generation sequencing, using a panel of 27 genes
      involved in neonatal jaundice and hemolytic anemia revealed four previously
      described heterozygous variations, which we postulate resulted in increased
      bilirubin production from hemolysis, plus retarded bilirubin uptake and
      conjugation. Mutations were found in the erythrocyte membrane protein band 4.1
      gene (EPB41), the alpha-spectrin gene (SPTA1), the gene encoding the enzyme for
      bilirubin conjugation (UGT1A1), and the gene encoding a transporter of bilirubin
      from the blood into hepatocytes (SLCO1B1).

PMID- 25758004
TI  - Comparison of neonatal outcomes in macrosomic infants of diabetic and non
      diabetic mothers.
AB  - OBJECTIVE: To compare the neonatal outcomes in macrosomic term infants of
      diabetic mothers and non-diabetic mothers. METHODS: This is a retrospective
      survey of all live-born term singletons with a birth weight >=4000 g, admitted at
      Tianjin Medical University General Hospital between 2010 and 2013. Data collected
      for the mothers included age, parity, gestational age, method of glycemic control
      and mode of delivery. Data for the infants included sex, birth weight, birth
      length, duration of hospital stay and laboratory tests. Outcomes were compared
      between infants of diabetic mothers (IDMs) and infants of non-diabetic mothers
      (Non-IDMs). All data were analyzed using Statistical Package for Social Sciences
      (SPSS) 17.0. RESULTS: One hundred and eleven infant-mother pairs met the
      inclusion criteria. Fifty-seven were IDMs while 54 were non-IDMs. Seven (12.28%)
      of the IDMs were delivered vaginally while 50 (87.72%) were delivered via
      Caesarian section (CS). Seventeen (31.48%) of the non-IDMs were delivered
      vaginally while 37 (68.51%) were delivered by CS. Respiratory distress was the
      most common morbidity affecting 52.6% of the IDMs and 40.7% of the non-IDMs.
      Hyperbilirubinemia was observed in 49.1% of the IDMs and 14.8% of the non-IDMs.
      Hypoglycemia affected 38.6% of the IDMs and 7.4% of the non-IDMs. Cardiac enzymes
      were higher in IDMs than in non-IDMs. On average, IDMs had a longer duration of
      hospital stay. CONCLUSION: Macrosomic IDMs in comparison to macrosomic non-IDMs
      are at an increased risk for adverse neonatal outcomes.

PMID- 25758005
TI  - Discontinuing caffeine in preterm infants at 33-35 weeks corrected gestational
      age: Failure rate and predictive factors.
AB  - OBJECTIVE: To examine the success rate of our current practice of discontinuing
      caffeine at 33 0/7-35 6/7 weeks post menstrual age (PMA), as well as factors that
      predict the success or failure of discontinuation. STUDY DESIGN: A retrospective
      chart review of infants born before 34 weeks gestational age between 2006-2012.
      Data collected included demographics, and other comorbidities mainly
      complications of prematurity. RESULTS: 647 treated infants had caffeine
      discontinued at 33-35 PMA before discharge or transfer. 64 (10%) infants failed
      discontinuation and had caffeine restarted. Most (77%) of those who failed
      started having monitor alarms within 7 days of discontinuation. BPD and Hispanic
      ethnicity were predictive of weaning failure (p < 0.05). CONCLUSION: Caffeine can
      be discontinued at 33-35 weeks PMA with a failure rate of 10%. BPD and Hispanic
      ethnicity are predictive of failure. It is generally safe to discharge infants
      seven days after the caffeine was discontinued if no significant monitor events
      occur during that time.

PMID- 25758006
TI  - Report of a pilot study of Cooling four preterm infants 32-35 weeks gestation
      with HIE.

PMID- 25758007
TI  - Tubal handling significantly affects site assignment in non-uterine high-grade
      serous carcinoma.

PMID- 25758008
TI  - Generation of electrospun nanofibers with controllable degrees of crimping
      through a simple, plasticizer-based treatment.
AB  - Electrospun nanofibers with controllable degrees of crimping are fabricated by
      simply exposing the samples to a plasticizer at preset shrinkage ratios. Compared
      with their straight counterparts, the crimped nanofibers are able to mechanically
      mimic native tendon tissue and better protect tendon fibroblasts under uniaxial
      strains. 

PMID- 25758009
TI  - Adaptive Evolution as a Predictor of Species-Specific Innate Immune Response.
AB  - It has been proposed that positive selection may be associated with protein
      functional change. For example, human and macaque have different outcomes to HIV
      infection and it has been shown that residues under positive selection in the
      macaque TRIM5alpha receptor locate to the region known to influence species
      specific response to HIV. In general, however, the relationship between sequence
      and function has proven difficult to fully elucidate, and it is the role of large
      scale studies to help bridge this gap in our understanding by revealing major
      patterns in the data that correlate genotype with function or phenotype. In this
      study, we investigate the level of species-specific positive selection in innate
      immune genes from human and mouse. In total, we analyzed 456 innate immune genes
      using codon-based models of evolution, comparing human, mouse, and 19 other
      vertebrate species to identify putative species-specific positive selection. Then
      we used population genomic data from the recently completed Neanderthal genome
      project, the 1000 human genomes project, and the 17 laboratory mouse genomes
      project to determine whether the residues that were putatively positively
      selected are fixed or variable in these populations. We find evidence of species
      specific positive selection on both the human and the mouse branches and we show
      that the classes of genes under positive selection cluster by function and by
      interaction. Data from this study provide us with targets to test the
      relationship between positive selection and protein function and ultimately to
      test the relationship between positive selection and discordant phenotypes. 

PMID- 25758010
TI  - Model-based verification of hypotheses on the origin of modern Japanese revisited
      by Bayesian inference based on genome-wide SNP data.
AB  - Various hypotheses for the peopling of the Japanese archipelago have been
      proposed, which can be classified into three models: transformation, replacement,
      and hybridization. In recent years, one of the hybridization models ("dual
      structure model") has been widely accepted. According to this model, Neolithic
      hunter-gatherers known as Jomon, who are assumed to have originated in southeast
      Asia and lived in the Japanese archipelago greater than 10,000 years ago, admixed
      with an agricultural people known as Yayoi, whom were migrants from the East
      Asian continent 2,000-3,000 years ago. Meanwhile, some anthropologists propose
      that rather, morphological differences between the Jomon and Yayoi people can be
      explained by microevolution following the lifestyle change. To resolve this
      controversy, we compared three demographic models by approximate Bayesian
      computation using genome-wide single nucleotide polymorphism (gwSNP) data from
      the Ainu people who are thought to be direct descendants of indigenous Jomon. If
      we assume Chinese people sampled in Beijing from HapMap have the same ancestry as
      Yayoi, then the hybridization model is predicted to be between 29 and 63 times
      more likely than the replacement and transformation models, respectively.
      Furthermore, our data provide strong support for a model in which the Jomon
      lineages had population structure diversified in local areas before the admixture
      event. Initial divergence between the Jomon and Yayoi ancestries was dated to
      late Pleistocene, followed by the divergence of Jomon lineages at early Holocene.
      These results suggest gwSNP data provides a detailed picture of the complex
      hybridization model for Japanese population history. 

PMID- 25758012
TI  - Vesicocutaneous fistula presenting 17 years post-radiotherapy for prostate
      cancer.

PMID- 25758013
TI  - The man behind the name Joel - a personal encounter.

PMID- 25758011
TI  - Should we use statins in all patients with chronic kidney disease without
      dialysis therapy? The current state of knowledge.
AB  - PURPOSE: The aim of this article was to present the most important matters
      associated with dyslipidemia treatment in CKD patients. Moreover, the most
      important recommendations of the current (2013) KDIGO clinical practice guideline
      for lipid management in chronic kidney disease are presented. METHODS: Authors
      looked through the most recent large clinical trials and meta-analyses and
      presented their results. We searched using the electronic databases [MEDLINE,
      EMBASE, Scopus, DARE]. Additionally, abstracts from national and international
      cardiovascular meetings were studied. RESULTS: Analysis results suggest that
      statins exert beneficial effects on kidney since they considerably reduce 24 h
      urinary protein excretion and are associated with a rise in GFR. Beneficial
      effects of statins may be influenced by kidney disease stage, doses of medicine
      and treatment duration. Data suggest that statins are effective and safe for
      secondary prevention of CV events in individuals with mild CKD. Patients treated
      with statins had decreased frequency of major atherosclerotic events compared
      with placebo, reduced risk of CV mortality and deaths from all causes.
      CONCLUSIONS: Meta-analyses results suggest that statins are associated with lipid
      lowering, cardiovascular and anti-proteinuric benefits in CKD patients. However,
      their effects on overall and cardiovascular mortality are much less obvious.
      Bearing in mind the advantageous effects and low risk of adverse effects, it
      seems that mild renal impairment should not exclude these patients from receiving
      a statin. However, because CKD patients in stages III-V are underrepresented in
      clinical trials, administration of statins to these patients who have not yet had
      a vascular event remains controversial.

PMID- 25758014
TI  - Ageing and reproduction: antioxidant supplementation alleviates telomere loss in
      wild birds.
AB  - Reproduction is inherently costly. Environmental stressors, such as infection and
      limited food resources, can compromise investment at each breeding attempt. For
      example, recent data on captive birds showed that increased reproductive effort
      accelerates ageing. However, the effects of nutritional status and infection on
      ageing remain unknown. Telomeres function as protective caps at the ends of
      eukaryotic chromosomes, and changes in telomere length is a commonly used proxy
      for ageing. To partially address the mechanisms of ageing following reproduction,
      we supplemented, medicated or administered a combined treatment to wild blue tits
      (Cyanistes caeruleus) breeding in central Spain during 2012. The nutritional
      supplement consisted of two different antioxidants, whereas the medication was an
      antimalarial treatment against blood parasites. We evaluated the effect of these
      manipulations on reproductive success and parasite loads in the first breeding
      season, and on changes in telomere length between two consecutive breeding
      seasons. Supplemented birds showed no reduction in blood parasite infections in
      2012, although they exhibited higher body mass and fledging success. The
      antimalarial drugs reduced infections by several parasite species, but this had
      no effect on fitness parameters. In the following season, telomeres from
      supplemented birds had shortened less. Altogether, we found that supplementation
      with antioxidants provided fitness benefits in the short term and reduced
      telomere loss a year following treatment. Our results provide indirect empirical
      support for accelerated telomere loss as a cost of reproduction.

PMID- 25758015
TI  - Taking part in Nordic collaboration; nursing students' experiences and
      perceptions from a learning perspective: A qualitative study.
AB  - BACKGROUND: Nordic networking of different kinds has a long tradition aiming to
      increase collaboration and understanding between citizens in different countries.
      Cultural competence in relation to health care and nursing is important for
      clinical nurses and is a central issue in nurse education. OBJECTIVE: To gain an
      understanding of what nurse students experienced and learned during an intensive
      course in diabetes together with students and nurse educators from Denmark,
      Finland, Iceland, Norway, Sweden and the Faroe Islands. METHODS: In 2012, an
      intensive course within the Nordic network, Nordkvist, was conducted in Faroe
      Islands with the theme "Nursing - to live a good life with diabetes". To answer
      the objective of the study, 26 students conducted written reflections based on
      two questions. The data was analyzed using qualitative content analysis. RESULTS:
      Through meetings with nurse students and educators from the Nordic countries the
      intensive course strengthened the students' identification with the nursing
      profession. The students gained new perspectives on diabetes, such as how complex
      it can be to live with a chronic illness. Because of the difficulties in
      understanding one another and because of different mother tongues, the students
      gained a better understanding of patients' vulnerability in relation to hospital
      jargon and how it felt to be in an unfamiliar place. CONCLUSIONS: The intensive
      course increased the students' personal and professional growth, cross-cultural
      competence, and their identification with nursing. Students' understanding of
      health care in the Nordic countries improved as similarities and differences were
      recognized.

PMID- 25758016
TI  - Alcohol problems in a remand Scottish prisoner population.
AB  - PURPOSE: Alcohol misuse is internationally recognised as a major public health
      problem. The link between alcohol and crime is strong and offenders have a higher
      prevalence of alcohol problems when compared with the general population. Alcohol
      related crime is estimated to cost the Scottish economy over L700 m per annum.
      The purpose of this paper is to measure the nature and prevalence of Alcohol Use
      Disorders (AUDs) in adult male prisoners on remand in a prison in Scotland.
      DESIGN/METHODOLOGY/APPROACH: Using the Alcohol Use Disorders Identification Test
      (AUDIT) screening tool, all new remand prisoners were screened over a two week
      period. FINDINGS: Prevalence of alcohol problems within the sample was high: 73
      per cent of the sample was identified with an AUD, with 43 per cent with scores
      indicating possible alcohol dependence. ORIGINALITY/VALUE: This is the first
      study to focus solely on a remand prisoner population and the results show high
      levels of need. The criminal justice setting is ideally placed to identify and
      treat alcohol problems in this hard to reach population.

PMID- 25758017
TI  - Detainees in police custody: results of a health needs assessment in Northumbria,
      England.
AB  - PURPOSE: The purpose of this paper is to assess the health needs of detainees in
      police custody in Northumbria, England, and to identify any gaps in, or possible
      improvements to, the current model of healthcare provision.
      DESIGN/METHODOLOGY/APPROACH: The current model of service provision was
      investigated using a combination of existing literature, and interviews with key
      members of staff. In addition, researchers examined the custody records of a
      stratified random sample of 1,917 records from 2010 and 2011. Data were collected
      from the risk assessments completed by Custody Sergeants, and any associated
      records of medical assessments by Forensic Medical Examiners (FME). FINDINGS:
      Detainees experience a wide range of health problems. Delivery of healthcare in
      custody could be improved through increasing the skill-mix in this setting,
      computerising FME records and improving communication between agencies. Research
      limitations/implications - The police did not always record the reason why a
      forensic medical examiner was called out, thus this aspect of data collection was
      limited. ORIGINALITY/VALUE: This health needs assessment will help to determine
      the way in which resources for health care in custody, currently held by the
      police, are reallocated once the funding transfers to the NHS in the near future.

PMID- 25758018
TI  - Barriers to implementing throughcare for problematic drug users in European
      prisons.
AB  - PURPOSE: The purpose of this paper is to analyse the extent of throughcare
      provision for prisoners with problematic drug use. Effective throughcare services
      have been recognised as important because they help to ensure that any progress
      in treatment made in prison is continued on release. Previous research
      demonstrates that examples of good practice in throughcare provision for
      prisoners with problematic drug use exist in many parts of the world. However,
      evidence from recent work carried out in Europe indicates that the implementation
      of throughcare services for this group of prisoners is limited and ineffective in
      some EU member states. This paper aims to explore the reasons for such failure
      and to identify the barriers to implementing effective throughcare for this
      particular group of prisoners. DESIGN/METHODOLOGY/APPROACH: This paper is drawn
      from research carried out as part of a European project funded by the Directorate
      General Justice of the European Commission. The project involved six partners
      from a range of different member states. The research involved a literature
      review, followed by in-depth interviews and focus groups with key stakeholders.
      Each partner carried out the qualitative research within their own country, in
      order to enable the team to capture local nuances. FINDINGS: The findings
      indicate that key barriers to implementation of effective throughcare are
      resources which impacts on the availability of support services, attitudes and
      training of staff and ultimately the continuity of care. ORIGINALITY/VALUE: This
      paper adds to the body of knowledge regarding the provision of effective
      throughcare to those with problematic drug use.

PMID- 25758019
TI  - Population pharmacokinetic models for cefuroxime and metronidazole used in
      combination as prophylactic agents in colorectal surgery: Model-based evaluation
      of standard dosing regimens.
AB  - The antibiotics used for prophylaxis in colorectal surgery must maintain
      appropriate plasma concentrations during the entire surgery to avoid surgical
      site infections caused by aerobes and anaerobes; cefuroxime plus metronidazole is
      one of the combinations used. The aim of this study was to evaluate the adequacy
      of cefuroxime plus metronidazole administration as prophylaxis in colorectal
      surgery. In total, 63 patients electively undergoing rectal or colon surgery were
      administered 1500mg of cefuroxime and 1500mg of metronidazole in 15-min and 1-h
      infusions, respectively, prior to surgery. Blood samples were withdrawn during
      and after surgery for determination of plasma concentrations by high-performance
      liquid chromatography. Population pharmacokinetic models were developed using
      NONMEM 7.2.0. Pharmacokinetic/pharmacodynamic (PK/PD) simulations were performed
      to explore the ability of different dosage regimens to achieve the
      pharmacodynamic targets. Pharmacokinetics for both antibiotics were best
      described by a two-compartment model. Elimination of cefuroxime was conditioned
      by creatinine clearance (CLCr). The half-life of cefuroxime was 1.5h for patients
      with normal renal function and 4.9h in patients with renal impairment.
      Elimination and distribution of metronidazole were affected by patient body
      weight (BW). PK/PD analysis revealed that a single-dose protocol of 1500mg of
      cefuroxime and metronidazole is adequate in short surgeries (<=2h). However, for
      longer surgeries, recommendations are suggested depending on the patient's CLCr
      and BW. Additional doses of cefuroxime are needed for patients with moderate
      renal impairment or those presenting normal renal function. For metronidazole, an
      additional dose is needed for patients with a BW of 90kg. 

PMID- 25758020
TI  - Trimethoprim/sulfamethoxazole resistance in clinical isolates of Burkholderia
      pseudomallei from Thailand.

PMID- 25758022
TI  - Designing optogenetically controlled RNA for regulating biological systems.
AB  - Light-responsive proteins have been used in the field of optogenetics to control
      cellular functions. However, surprisingly, analogous approaches to regulate and
      alter the functions of RNA molecules by light remain underdeveloped. RNA aptamers
      and RNA devices can perform diverse intracellular functions and are important
      tools in synthetic biology. This report explores the challenges of and potential
      strategies for engineering light regulation into functional RNAs in cells. We
      discuss approaches for using existing light-regulated proteins and small
      molecules to control RNA function in living cells. In addition, applications of
      light-regulated RNAs for synthetic biology and for studying functions of
      endogenously expressed RNAs are discussed. 

PMID- 25758021
TI  - The STING pathway and the T cell-inflamed tumor microenvironment.
AB  - A major subset of patients with advanced solid tumors show a spontaneous T cell
      inflamed tumor microenvironment, which has prognostic import and is associated
      with clinical response to immunotherapies. As such, understanding the mechanisms
      governing the generation of spontaneous T cell responses in only a subset of
      patients is critical for advancing immunotherapeutic approaches further. Here, we
      discuss the characteristics of T cell-inflamed versus non-inflamed tumors,
      including a type I interferon (IFN) signature associated with T cell priming
      against tumor antigens. We review recent findings that have pointed towards the
      STING (stimulator of interferon genes) pathway of cytosolic DNA sensing as an
      important innate immune sensing mechanism driving type I IFN production in the
      tumor context. Knowledge of this pathway is guiding the further development of
      novel immunotherapeutic strategies. 

PMID- 25758024
TI  - Synthesis and structural reconfirmation of bacillamide B.
AB  - A concise total synthesis of the natural product bacillamide B was accomplished
      in 30% overall yield starting from L-cystine. The key step was a one-pot four
      step process of thiazoline formation via a cascade disulfide
      cleavage/thiocarbonylation/Staudinger reduction/aza-Wittig reaction using beta
      azido disulfide and carboxylic acid as substrates. The absolute configuration of
      the natural bacillamide B was reconfirmed to be S and the specific optical
      rotation was revised to (-).

PMID- 25758023
TI  - Label-free profiling of white adipose tissue of rats exhibiting high or low
      levels of intrinsic exercise capacity.
AB  - Divergent selection has created rat phenotypes of high- and low-capacity runners
      (HCR and LCR, respectively) that have differences in aerobic capacity and
      correlated traits such as adiposity. We analyzed visceral adipose tissue of HCR
      and LCR using label-free high-definition MS (elevated energy) profiling. The
      running capacity of HCR was ninefold greater than LCR. Proteome profiling
      encompassed 448 proteins and detected 30 significant (p <0.05; false discovery
      rate <10%, calculated using q-values) differences. Approximately half of the
      proteins analyzed were of mitochondrial origin, but there were no significant
      differences in the abundance of proteins involved in aerobic metabolism. Instead,
      adipose tissue of LCR rats exhibited greater abundances of proteins associated
      with adipogenesis (e.g. cathepsin D), ER stress (e.g. 78 kDa glucose response
      protein), and inflammation (e.g. Ig gamma-2B chain C region). Whereas the
      abundance antioxidant enzymes such as superoxide dismutase [Cu-Zn] was greater in
      HCR tissue. Putative adipokines were also detected, in particular protein S100-B,
      was 431% more abundant in LCR adipose tissue. These findings reveal low running
      capacity is associated with a pathological profile in visceral adipose tissue
      proteome despite no detectable differences in mitochondrial protein abundance. 

PMID- 25758025
TI  - A commentary on "Involvement of activating ERK1/2 trough G protein coupled
      receptor 30 and estrogen receptor alpha/beta in low doses of bisphenol A
      promoting growth of Sertoli TM4 cells".

PMID- 25758026
TI  - Red blood cell as an adaptive optofluidic microlens.
AB  - The perspective of using live cells as lenses could open new revolutionary and
      intriguing scenarios in the future of biophotonics and biomedical sciences for
      endoscopic vision, local laser treatments via optical fibres and diagnostics.
      Here we show that a suspended red blood cell (RBC) behaves as an adaptive liquid
      lens at microscale, thus demonstrating its imaging capability and tunable focal
      length. In fact, thanks to the intrinsic elastic properties, the RBC can swell up
      from disk volume of 90 fl up to a sphere reaching 150 fl, varying focal length
      from negative to positive values. These live optofluidic lenses can be fully
      controlled by triggering the liquid buffer's chemistry. Real-time accurate
      measurement of tunable focus capability of RBCs is reported through dynamic
      wavefront characterization, showing agreement with numerical modelling. Moreover,
      in analogy to adaptive optics testing, blood diagnosis is demonstrated by
      screening abnormal cells through focal-spot analysis applied to an RBC ensemble
      as a microlens array. 

PMID- 25758027
TI  - The changes in cardiac physiology with aging and the implications for the
      treating oncologist.
AB  - The link between cancer, cardiovascular disease, and aging is well documented. In
      this review, we highlight the physiologic and pathologic changes associated with
      the cardiovascular aging process, the role they play when interfaced with various
      cancer therapies and the implications for the treating oncologist. 

PMID- 25758028
TI  - Reversible electrochemical actuation of metallic nanohoneycombs induced by
      pseudocapacitive redox processes.
AB  - Current metallic-based electrochemical actuators are limited to nanoporous
      gold/platinum with randomly distributed pores, where the charge-induced
      reversible strain is mainly due to the nonfaradic charging/discharging processes
      along the capacitive electrochemical double layer. Here, we report an
      electrochemical actuating property of nanohoneycomb-structured nickel, with the
      actuation mechanism mainly due to a pseudocapacitive behavior by means of
      reversible faradic redox reactions. By using a dual-template synthesis method, a
      bilayered cantilever, comprising a nanohoneycomb layer backed by a solid layer of
      the same metal, was fabricated. Reversible bending of the cantilever upon cyclic
      potential triggering was observed. The strain of the cantilever increases
      nonlinearly with both potential and charge due to redox reactions. The maximum
      strain that can be achieved under a certain scan rate complies with a linear
      relationship with the capacity. Benefiting from the stable Ni(II)/Ni(III) redox
      couples at the electrode surface, the reversible actuation is very stable in
      hydroxide solutions. 

PMID- 25758030
TI  - Synthesis, structure and reactivity of rare-earth metallacarborane alkyls
      [eta(1):eta(5)-O(CH2)2C2B9H9]Ln(sigma:eta(1)-CH2C6H4-o-NMe2)(THF)2.
AB  - Rare-earth metallacarborane alkyls can be stabilized by the incorporation of a
      functional sidearm into both pi and sigma ligands. Reaction of [Me3NH][7,8
      O(CH2)2-7,8-C2B9H10] with one equiv. of Ln(CH2C6H4-o-NMe2)3 gave metallacarborane
      alkyls [eta(1):eta(5)-O(CH2)2C2B9H9]Ln(sigma:eta(1)-CH2C6H4-o-NMe2)(THF)2 (Ln = Y
      (), Gd (), Er ()) via alkane elimination. They represent the first examples of
      rare-earth metallacarborane alkyls. Treatment of with RN[double bond, length as m
      dash]C[double bond, length as m-dash]NR (R = Cy, (i)Pr) or 2-benzoylpyridine
      afforded the corresponding mono-insertion products [eta(1):eta(5)
      O(CH2)2C2B9H9]Y[eta(2)-(RN)2C(CH2C6H4-o-NMe2)](DME) (R = Cy (), (i)Pr ()) or
      [eta(1):eta(5)-O(CH2)2C2B9H9]Y[C5H4NC(Ph)(CH2C6H4-o-NMe2)O](THF)2 (),
      respectively. Complex also reacted with ArNCO or ArNC (Ar = 2,6
      diisopropylphenyl, 2,6-dimethylphenyl) to give di-insertion products
      [eta(1):eta(5)-O(CH2)2C2B9H9]Y[OC([double bond, length as m
      dash]NC6H3Me2)N(C6H3Me2)C(CH2C6H4-o-NMe2)O](THF)2 () or [eta(1):eta(5)
      O(CH2)2C2B9H9]Y[C([double bond, length as m-dash]NC6H3(i)Pr2)C([double bond,
      length as m-dash]NC6H3(i)Pr2)(CH2C6H4-o-NMe2)](DME) (). These results showed that
      the reactivity pattern of the Ln-C sigma bond in rare-earth metallacarborane
      alkyls was dependent on the nature of the unsaturated organic molecules. New
      complexes were characterized by various spectroscopic techniques and elemental
      analysis. Some were further confirmed by single-crystal X-ray analysis. 

PMID- 25758029
TI  - High-speed GaN/GaInN nanowire array light-emitting diode on silicon(111).
AB  - The high speed on-off performance of GaN-based light-emitting diodes (LEDs) grown
      in c-plane direction is limited by long carrier lifetimes caused by spontaneous
      and piezoelectric polarization. This work demonstrates that this limitation can
      be overcome by m-planar core-shell InGaN/GaN nanowire LEDs grown on Si(111). Time
      resolved electroluminescence studies exhibit 90-10% rise- and fall-times of about
      220 ps under GHz electrical excitation. The data underline the potential of these
      devices for optical data communication in polymer fibers and free space. 

PMID- 25758031
TI  - Re: test of four colon cancer risk-scores in formalin fixed paraffin embedded
      microarray gene expression data.

PMID- 25758032
TI  - Response.

PMID- 25758035
TI  - Humoral immunity in tuberculosis.

PMID- 25758036
TI  - Falk Herbert Weih (1959-2014).

PMID- 25758040
TI  - Carbon p electron ferromagnetism in silicon carbide.
AB  - Ferromagnetism can occur in wide-band gap semiconductors as well as in carbon
      based materials when specific defects are introduced. It is thus desirable to
      establish a direct relation between the defects and the resulting ferromagnetism.
      Here, we contribute to revealing the origin of defect-induced ferromagnetism
      using SiC as a prototypical example. We show that the long-range ferromagnetic
      coupling can be attributed to the p electrons of the nearest-neighbor carbon
      atoms around the VSiVC divacancies. Thus, the ferromagnetism is traced down to
      its microscopic electronic origin. 

PMID- 25758041
TI  - Effects of Legume-Enriched Diet on Cardiometabolic Risk Factors among Individuals
      at Risk for Diabetes: A Crossover Study.
AB  - AIMS: First-degree relatives of patients with diabetes are at high risk for
      chronic diseases, including type 2 diabetes and obesity. Our purpose was to
      determine the effects of consuming 4 servings of legumes per week on lipid
      profiles, glycemic indices, and blood pressure of participants with family
      history of diabetes over 6 weeks of intervention. METHODS: A total of 26 first
      degree relatives of patients with diabetes (14 women and 12 men) participated in
      this randomized crossover clinical trial study. Participants were randomly
      assigned to a legume-enriched diet or habitual diet for 6 weeks. Paired t test
      and repeated measures analysis of variance were used to compare data for the 2
      experimental diets. RESULTS: The mean +/- SE of legumes intake during the legume
      phase was 111.12 +/- 10.53 g/day that was significantly higher (p < 0.001) than
      the amounts of legumes during habitual diet (50.73 +/- 7.10 g/d). Percentage
      changes for cardiovascular disease risk factors did not change significantly
      following 6 weeks of legume consumption. CONCLUSIONS: Consumption of 4 servings
      of legumes per week had no significant effect on anthropometric measurements,
      glycemic indices, and lipid profiles of participants with family history of
      diabetes, though it could reduce systolic and diastolic blood pressure at a
      marginally significant level.

PMID- 25758042
TI  - Complete mitochondrial genome of Grey-headed Lapwing Vanellus cinereus
      (Ciconiiformes: Charadriidae).
AB  - The Grey-headed Lapwing (Vanellus cinereus) is a Vanellus bird belonging to the
      group Ciconiiformes, which breeds in northeast China and Japan. In this study, we
      sequenced its complete mitochondrial genome by PCR-based method. The
      mitochondrial DNA is packaged in a compact 17,135 based pair (bp) circular
      molecule with A + T content of 55.14%. It contains 37 typical mitochondrial
      genes, including 13 protein-coding genes, 2 rRNAs and 22 tRNAs and a non-coding
      control region (D-loop). All protein-coding genes are initiated by ATG codon,
      except for the COI gene and ND5 gene starting with GTG codon, and ND3 uses ATC
      codon. TAA is the most frequent stop codon. All tRNAs possess the classic
      cloverleaf secondary structure except for tRNA(Ser(AGY)) and tRNA(Leu(CUN)),
      which lack the ''DHU'' stem. The D-loop is a 1563 bp long A + T-rich region,
      which is located between tRNA(Glu) and tRNA(Phe).

PMID- 25758043
TI  - Complete mitochondrial genome of the versicoloured emerald hummingbird Amazilia
      versicolor, a polymorphic species.
AB  - The genome of the versicoloured emerald hummingbird (Amazilia versicolor) was
      partially sequenced in one-sixth of an Illumina HiSeq lane. The mitochondrial
      genome was assembled using MIRA and MITObim software, yielding a circular
      molecule of 16,861 bp in length and deposited in GenBank under the accession
      number KF624601. The mitogenome contained 13 protein-coding genes, 22 transfer
      tRNAs, 2 ribosomal RNAs and 1 non-coding control region. The molecule was
      assembled using 21,927 sequencing reads of 100 bp each, resulting in ~130 *
      coverage of uniformly distributed reads along the genome. This is the forth
      mitochondrial genome described for this highly diverse family of birds and may
      benefit further phylogenetic, phylogeographic, population genetic and species
      delimitation studies of hummingbirds.

PMID- 25758044
TI  - The complete mitochondrial genome of Fulica atra (Avian, Gruiformes, Rallidae).
AB  - To analyze the gene structure and the evolutionary roadmap of Fulica atra, the
      complete mitogenome is sequenced. It is composed of 37 genes and 1 control
      region, and the structure and arrangement of all genes are identical to other
      Rallidae. The comparative mitogenome revealed that the start codon and stop codon
      varied in Rallidae, and the gene lengths are different in ND2, COX1, ND3, ND5 and
      CYTB due to incompleteness of stop codon, frameshift mutation and various numbers
      of amino acids. We analyzed the correlation between phylogeny and gene
      characteristic in Rallidae with respect to the usage of start/stop codon and gene
      length, but no correlation was found. It indicates these discrepancies might
      happen independently. This work can afford an in-depth insight of phyletic
      evolution in Rallidae.

PMID- 25758045
TI  - The complete mitochondrial genome sequence of the Xizang Plateau frog, Nanorana
      parkeri (Anura: Dicroglossidae).
AB  - The Xizang Plateau frog (Nanorana parkeri) belongs to the family Dicroglossidae,
      which distributes in southern and eastern Xizang, southern-most Qinghai in China,
      high elevations of north-central Nepal, Himalayan Bhutan, northeastern Kashmir
      and India. In this study, the complete mitochondrial genome of N. parkeri was
      sequenced. The mitogenome was 17,837 bp in length, consisting of 13 protein
      coding genes, 22 transfer RNA (tRNA) genes, two ribosomal RNA genes, and a non
      coding control region (CR). As in other vertebrates, most mitochondrial genes are
      encoded on the heavy strand, except for ND6 and eight tRNA genes, which are
      encoded on the light strand. The overall base composition of the N. parkeri is A:
      27.7 % A, T: 30.1 % T, C: 26.6% and G: 15.6%. The alignment of the Nanorana
      species CRs exhibited high genetic variability and rich A + T content. In
      comparison with the mtDNA sequences typical of vertebrates, a tandem duplication
      of the tRNA(Met) gene and a rearrangement of the tRNA(Thr), tRNA(Pro) and
      tRNA(Leu) (CUN) genes were found. The complete mitogenome of N. parkeri can
      provided an important data for the studies on phylogenetic relationship and
      population genetics to further explore the taxonomic status of this species.

PMID- 25758046
TI  - The complete mitochondrial genome of the rare and endangered Orthotrichum rogeri
      (Orthotrichaceae, Bryophyta).
AB  - The mitogenome of the Orthotrichum rogeri (GenBank accession number KM873610) has
      a total length of 106,634 bp and consist of 40 protein-coding genes, 3 ribosomal
      RNA (rRNA) and 24 transfer RNA. The gene order is identical to other known moss
      mitogenomes. A complete mitochondrial genome sequence of O. rogeri will help the
      development of primers for examining mitochondrial variation across bryophytes.

PMID- 25758047
TI  - The complete mitochondrial genome of pike-perch, Sander lucioperca (Perciformes:
      Percidae).
AB  - The complete mitochondrial genome of Sander lucioperca has been sequenced and
      analyzed in this study. It was a circular double-stranded DNA molecule of 16,541
      base pairs (bp) in length and exhibited 37 typical animal mitochondrial genes.
      The gene order and base composition were similar to those of other percid
      species. All protein-coding genes were initiated with ATG except for COX 1, which
      began with GTG instead. However, the termination codons of 13 protein-coding
      genes varied with TAG, TAA, TA or T. Within CR, we detected five copies of 10 bp
      tandemly repeated sequences domain, which immediately followed the tRNA(Pro).
      These mitogenome sequence data would contribute to better understanding
      phylogenetic relationships and population genetics of the family Percidae.

PMID- 25758048
TI  - The complete mitochondrial genome of the facultative entomopathogenic nematode
      Oscheius chongmingensis (Rhabditida: Rhabditidae).
AB  - We determined the complete mitochondrial genome of the facultative
      entomopathogenic nematode Oscheius chongmingensis. The mitogenome length was
      15,413 bp and similar to other Rhabditids contains genes for 2 rRNAs, 22 tRNAs,
      and 12 proteins (ATPase subunit 8 is missing). Predicted tRNAs indicated the
      secondary structure typical for chromadorean nematodes. Gene order is similar to
      that observed in the genus Caenorhabditis. The control AT-rich region is
      considerably large (2061 bp, 84% of AT), positioned in between tRNA(Ala) and
      tRNA(Pro) and has several microsatellite-like (AT)n elements.

PMID- 25758050
TI  - Segmentation of biological multivariate time-series data.
AB  - Time-series data from multicomponent systems capture the dynamics of the ongoing
      processes and reflect the interactions between the components. The progression of
      processes in such systems usually involves check-points and events at which the
      relationships between the components are altered in response to stimuli.
      Detecting these events together with the implicated components can help
      understand the temporal aspects of complex biological systems. Here we propose a
      regularized regression-based approach for identifying breakpoints and
      corresponding segments from multivariate time-series data. In combination with
      techniques from clustering, the approach also allows estimating the significance
      of the determined breakpoints as well as the key components implicated in the
      emergence of the breakpoints. Comparative analysis with the existing alternatives
      demonstrates the power of the approach to identify biologically meaningful
      breakpoints in diverse time-resolved transcriptomics data sets from the yeast
      Saccharomyces cerevisiae and the diatom Thalassiosira pseudonana. 

PMID- 25758049
TI  - Transcriptome analysis of thermophilic methylotrophic Bacillus methanolicus MGA3
      using RNA-sequencing provides detailed insights into its previously uncharted
      transcriptional landscape.
AB  - BACKGROUND: Bacillus methanolicus MGA3 is a thermophilic, facultative ribulose
      monophosphate (RuMP) cycle methylotroph. Together with its ability to produce
      high yields of amino acids, the relevance of this microorganism as a promising
      candidate for biotechnological applications is evident. The B. methanolicus MGA3
      genome consists of a 3,337,035 nucleotides (nt) circular chromosome, the 19,174
      nt plasmid pBM19 and the 68,999 nt plasmid pBM69. 3,218 protein-coding regions
      were annotated on the chromosome, 22 on pBM19 and 82 on pBM69. In the present
      study, the RNA-seq approach was used to comprehensively investigate the
      transcriptome of B. methanolicus MGA3 in order to improve the genome annotation,
      identify novel transcripts, analyze conserved sequence motifs involved in gene
      expression and reveal operon structures. For this aim, two different cDNA library
      preparation methods were applied: one which allows characterization of the whole
      transcriptome and another which includes enrichment of primary transcript 5'
      ends. RESULTS: Analysis of the primary transcriptome data enabled the detection
      of 2,167 putative transcription start sites (TSSs) which were categorized into
      1,642 TSSs located in the upstream region (5'-UTR) of known protein-coding genes
      and 525 TSSs of novel antisense, intragenic, or intergenic transcripts. Firstly,
      14 wrongly annotated translation start sites (TLSs) were corrected based on
      primary transcriptome data. Further investigation of the identified 5'-UTRs
      resulted in the detailed characterization of their length distribution and the
      detection of 75 hitherto unknown cis-regulatory RNA elements. Moreover, the exact
      TSSs positions were utilized to define conserved sequence motifs for translation
      start sites, ribosome binding sites and promoters in B. methanolicus MGA3. Based
      on the whole transcriptome data set, novel transcripts, operon structures and
      mRNA abundances were determined. The analysis of the operon structures revealed
      that almost half of the genes are transcribed monocistronically (940), whereas
      1,164 genes are organized in 381 operons. Several of the genes related to
      methylotrophy had highly abundant transcripts. CONCLUSION: The extensive insights
      into the transcriptional landscape of B. methanolicus MGA3, gained in this study,
      represent a valuable foundation for further comparative quantitative
      transcriptome analyses and possibly also for the development of molecular biology
      tools which at present are very limited for this organism.

PMID- 25758051
TI  - Differential expression of microRNAs in postoperative radiotherapy sensitive and
      resistant patients with glioblastoma multiforme.
AB  - Glioblastoma multiforme (GBM) is the most malignant primary brain tumor and more
      resistant to radiotherapy. However, hetero-radiosensitivity occurs in different
      patients. MicroRNAs (miRNAs) play important roles in the initiation and
      progression of a multitude of tumors. The study aims to examine the different
      microRNAs expression profiles of postoperative radiotherapy sensitive and
      resistant patients with GBM, to make an inquiry about their potential role and
      discover a certain set of radio-sensitivity markers. Three paired samples from
      six GBM patients who had only been treated with postoperative radiotherapy were
      selected, and then, they were divided into radiotherapy sensitive group and
      resistant group according to their overall survivals, local recurrence rates, and
      Karnofsky Performance Scale scores. Expression profiles of miRNAs in these two
      groups were determined by the method of microarray assay. Comparing with
      resistant patients, 13 miRNAs were significantly upregulated and 10 miRNAs were
      greatly downregulated in sensitive group. Among them, four miRNAs were validated
      by quantitative RT-PCR. The differentially expressed miRNAs and their putative
      target genes were revealed by bioformatic analysis to play a role in cell
      signaling, proliferation, aging, and death. High-enrichment pathway analysis
      identified that some classical pathways participated in numerous metabolic
      processes, especially in cell cycle regulation, such as mTOR, MAPK, TGF-beta, and
      PI3K-Akt signaling pathways. Our research will contribute to identifying clinical
      diagnostic markers and therapeutic targets in the treatment of GBM by
      postoperative radiotherapy.

PMID- 25758052
TI  - The clinicopathological significance and potential drug target of E-cadherin in
      NSCLC.
AB  - Human epithelial cadherin (E-cadherin), a member of transmembrane glycoprotein
      family, encoded by the E-cadherin gene, plays a key role in cell-cell adhesion,
      adherent junction in normal epithelial tissues, contributing to tissue
      differentiation and homeostasis. Although previous studies indicated that
      inactivation of the E-cadherin is mainly induced by hypermethylation of E
      cadherin gene, evidence concerning E-cadherin hypermethylation in the
      carcinogenesis and development of non-small cell lung carcinoma (NSCLC) remains
      controversial. In this study, we conducted a meta-analysis to quantitatively
      evaluate the effects of E-cadherin hypermethylation on the incidence and
      clinicopathological characteristics of NSCLC. A comprehensive search of PubMed
      and Embase databases was performed up to October 2014. Analyses of pooled data
      were performed. Odds ratios (ORs) were calculated and summarized. Our meta
      analysis combining 18 published articles demonstrated that the hypermethylation
      frequencies in NSCLC were significantly higher than those in normal control
      tissues, OR = 3.55, 95 % confidence interval (CI) = 1.98-6.36, p < 0.0001.
      Further analysis showed that E-cadherin hypermethylation was not strongly
      associated with the sex or smoking status in NSCLC patients. In addition, E
      cadherin hypermethylation was also not strongly associated with pathological
      types, differentiated status, clinical stages, or metastatic status in NSCLC
      patients. The results from the current study indicate that the hypermethylation
      frequency of E-cadherin in NSCLC is strongly associated with NSCLC incidence and
      it may be an early event in carcinogenesis of NSCLC. We also discussed the
      potential value of E-cadherin as a drug target that may bring new direction and
      hope for cancer treatment through gene-targeted therapy.

PMID- 25758053
TI  - Prognostic significance of Ku80 in pT2N0M0 esophageal squamous cell carcinoma
      after Ivor-Lewis esophagectomy.
AB  - Recent studies have shown that Ku80, a DNA repair protein, was involved in
      progression of malignant tumors. This study aimed to clarify the
      clinicopathological significance and prognostic value of Ku80 in pT2N0M0
      esophageal squamous cell carcinoma (ESCC). We enrolled 217 patients with pT2N0M0
      midthoracic ESCC who had undergone Ivor-Lewis esophagectomy. The expression
      profile of Ku80 was examined by immunohistochemistry. The results were correlated
      with the clinicopathological variables, overall survival (OS) and disease-free
      survival (DFS), in pT2N0M0 ESCC patients. The expression of Ku80 were higher in
      ESCC tissues than the corresponding health esophageal mucosa (P < 0.001).
      Clinically, the Ku80 expression levels were significantly related to tumor size
      (P = 0.018), differentiation degree (P = 0.010), and tumor-node-metastasis (TNM)
      stage (P = 0.001). Subsequent multivariate analysis demonstrated that tumor size,
      differentiation degree, TNM stage, and Ku80 expression were independent
      prognostic factors for the OS and the DFS of pT2N0M0 ESCC patients. Our data
      indicated that Ku80 expression level associates with key clinicopathological
      features and is an independent predictor of the OS and the DFS in pT2N0M0 ESCC
      patients.

PMID- 25758054
TI  - Cognitive constraints on motor imagery.
AB  - Executed bimanual movements are prepared slower when moving to symbolically
      different than when moving to symbolically same targets and when targets are
      mapped to target locations in a left/right fashion than when they are mapped in
      an inner/outer fashion [Weigelt et al. (Psychol Res 71:238-447, 2007)]. We
      investigated whether these cognitive bimanual coordination constraints are
      observable in motor imagery. Participants performed fast bimanual reaching
      movements from start to target buttons. Symbolic target similarity and mapping
      were manipulated. Participants performed four action conditions: one execution
      and three imagination conditions. In the latter they indicated starting, ending,
      or starting and ending of the movement. We measured movement preparation (RT),
      movement execution (MT) and the combined duration of movement preparation and
      execution (RTMT). In all action conditions RTs and MTs were longer in movements
      towards different targets than in movements towards same targets. Further, RTMTs
      were longer when targets were mapped to target locations in a left/right fashion
      than when they were mapped in an inner/outer fashion, again in all action
      conditions. RTMTs in imagination and execution were similar, apart from the
      imagination condition in which participants indicated the start and the end of
      the movement. Here MTs, but not RTs, were longer than in the execution condition.
      In conclusion, cognitive coordination constraints are present in the motor
      imagery of fast (<1600 ms) bimanual movements. Further, alternations between
      inhibition and execution may prolong the duration of motor imagery. 

PMID- 25758055
TI  - Microbial colonization of irradiated pathogenic yeast to catheter surfaces:
      Relationship between adherence, cell surface hydrophobicity, biofilm formation
      and antifungal susceptibility. A scanning electron microscope analysis.
AB  - PURPOSE: Technological advances such as long-term indwelling catheters have
      created milieu in which infections are a major complication. Thus it is essential
      to be able to recognize, diagnose, and treat infections occurring in
      immunocompromised patients. MATERIALS AND METHODS: Adherence assay and
      quantitation of biofilms was performed by a spectrophotometric method,
      hydrophobicity was evaluated by adhesion to p-xylene. The minimum inhibitory
      concentration (MIC) of Nystatin was carried out by a well dilution method.
      RESULTS: Out of 100 bladder cancer patients, 23 pathogenic yeast isolates were
      identified. The samples were taken from urinary catheters and urine collected
      from their attached drainage bags. Pathogenic yeast identified were species of
      Candida, Cryptococcus, Saccharomyces, Blastoschizomyces, Trichosporn, Hansenula,
      Prototheca and Rhodotorula. With the exception of Rhodotorula minuta, the yeast
      were sensitive to the antimycotic agent (Nystatin) used before and after in vitro
      gamma irradiation at 24.41 Gy as measured by a disc diffusion method. All tested
      yeast strains were slime producers and showed positive adherence reactions. There
      were considerable differences in adherence measurements after irradiation. An
      increase in adherence measurement values (using a spectrophotometric method)
      after irradiation were detected in four strains whereas eight other strains
      showed a reduction in their adherence reaction. The cell surface hydrophobicity
      (CSH) was evaluated by adhesion to p-xylene. Candida tropicalis showed a
      hydrophobic reaction with an increase in the cell surface hydrophobicity after
      irradiation. Scanning electron microscopy of irradiated C. tropicalis showed
      marked abnormalities in cell shape and size with significant reduction in
      adherence ability at the MIC level of Nystatin (4 MUg/ml). CONCLUSIONS: More
      basic research at the level of pathogenesis and catheter substance is needed to
      design novel strategies to prevent fungal adherence and to inhibit biofilm
      formation.

PMID- 25758056
TI  - Cortical Surface Area Differentiates Familial High Risk Individuals Who Go on to
      Develop Schizophrenia.
AB  - BACKGROUND: Schizophrenia is associated with structural brain abnormalities that
      may be present before disease onset. It remains unclear whether these represent
      general vulnerability indicators or are associated with the clinical state
      itself. METHODS: To investigate this, structural brain scans were acquired at two
      time points (mean scan interval 1.87 years) in a cohort of individuals at high
      familial risk of schizophrenia (n = 142) and control subjects (n = 36). Cortical
      reconstructions were generated using FreeSurfer. The high-risk cohort was
      subdivided into individuals that remained well during the study, individuals that
      had transient psychotic symptoms, and individuals that subsequently became ill.
      Baseline measures and longitudinal change in global estimates of thickness and
      surface area and lobar values were compared, focusing on overall differences
      between high-risk individuals and control subjects and then on group differences
      within the high-risk cohort. RESULTS: Longitudinally, control subjects showed a
      significantly greater reduction in cortical surface area compared with the high
      risk group. Within the high-risk group, differences in surface area at baseline
      predicted clinical course, with individuals that subsequently became ill having
      significantly larger surface area than individuals that remained well during the
      study. For thickness, longitudinal reductions were most prominent in the frontal,
      cingulate, and occipital lobes in all high-risk individuals compared with control
      subjects. CONCLUSIONS: Our results suggest that larger surface areas at baseline
      may be associated with mechanisms that go above and beyond a general familial
      disposition. A relative preservation over time of surface area, coupled with a
      thinning of the cortex compared with control subjects, may serve as vulnerability
      markers of schizophrenia.

PMID- 25758058
TI  - Effects of desvenlafaxine on blood pressure in patients treated for major
      depressive disorder: a pooled analysis.
AB  - OBJECTIVE: To evaluate the effect of the serotonin-norepinephrine re-uptake
      inhibitor desvenlafaxine on blood pressure and incidence of new onset
      hypertension in pooled short-term studies and in two longer-term, randomized
      withdrawal studies. RESEARCH DESIGN AND METHODS: Data from patients randomly
      assigned to desvenlafaxine 10 mg to 400 mg/day or placebo in 11 short-term (8-12
      weeks), fixed-dose, double-blind, placebo-controlled studies of major depressive
      disorder (MDD) were pooled for analysis; two desvenlafaxine randomized withdrawal
      studies (36 and 46 weeks) were analyzed separately. CLINICAL TRIAL REGISTRATION:
      www.clinicaltrials.gov , NCT00072774, NCT00073762, NCT00277823, NCT00300378,
      NCT00384033, NCT00798707, NCT00863798, NCT01121484, NCT00824291, NCT01432457,
      NCT00075257, NCT00887224. MAIN OUTCOME MEASURES: Outcomes included change from
      baseline in supine systolic blood pressure (SSBP) and supine diastolic blood
      pressure (SDBP), assessed using a mixed model repeated measures (MMRM) analysis,
      and incidence of hypertension (defined as three consecutive second SDBP measures
      >=90 mm Hg AND increase of >=10 mm Hg from baseline and/or SSBP >=140 mm Hg AND
      increase of >=10 mm Hg), analyzed using Cochran Mantel Hanzael tests. Potential
      predictors of change in SSBP and SDBP at LOCF were examined by including
      predictor variables in a regression model. RESULTS: In the pooled, short-term
      studies, mean changes from baseline over time in SSBP and SDBP were statistically
      significant compared with placebo for the desvenlafaxine doses of 10 mg/day or
      greater for SSBP (p <= 0.0004; MMRM) and 25 mg/day or greater for SDBP (p <=
      0.0449; MMRM). The proportion of patients with new onset hypertension differed
      significantly from placebo for the 50, 200, and 400 mg/day doses (1.9%, 2.4%,
      4.8%, respectively, vs 0.8%; all p <= 0.0244). Predictors of change in BP
      included baseline SDBP, baseline SSBP, dose, body mass index, gender, age, race,
      and history of hypertension. LIMITATIONS: Data were pooled from studies which
      differed somewhat in study design and patient demographics. None of the studies
      were originally designed to examine treatment effects on BP. Study entry criteria
      limit generalization of these results to medically stable patients with a primary
      diagnosis of MDD. CONCLUSIONS: Short-term desvenlafaxine treatment was associated
      with small but statistically significant increases in SSBP and SDBP.

PMID- 25758059
TI  - The topology of the Ehrenfest force density revisited. A different perspective
      based on Slater-type orbitals.
AB  - The topology of the Ehrenfest force density was studied with Slater-type orbitals
      (STO). At larger distances from the nuclei, STOs generate similar artefacts as
      noticed before with Gaussian-type orbitals. The topology of the Ehrenfest force
      density was found to be mainly homeomorphic with the topology of the electron
      density. For the first time, reliable integrations of several properties over
      force density atomic basins were performed successfully. Integration of the
      electron density of a number of hydrides, fluorides, and chlorides of first row
      elements over force density basins indicate substantial differences between the
      partial charges of the atoms as compared with those obtained from electron
      density basins. Calculations on saturated hydrocarbons confirm that the
      electronegativity of carbon atoms increases with increasing geometrical strain.
      Atomic interaction lines are observed to exist in the Ehrenfest force density
      between the hydrogen atoms of several so-called "congested" molecules, and also
      in some inclusion complexes of alkanes with helium. However, interaction lines
      are lacking in several other controversial cases.

PMID- 25758057
TI  - Prolonged Period of Cortical Plasticity upon Redox Dysregulation in Fast-Spiking
      Interneurons.
AB  - BACKGROUND: Oxidative stress and the specific impairment of perisomatic gamma
      aminobutyric acid circuits are hallmarks of the schizophrenic brain and its
      animal models. Proper maturation of these fast-spiking inhibitory interneurons
      normally defines critical periods of experience-dependent cortical plasticity.
      METHODS: Here, we linked these processes by genetically inducing a redox
      dysregulation restricted to such parvalbumin-positive cells and examined the
      impact on critical period plasticity using the visual system as a model (3-6
      mice/group). RESULTS: Oxidative stress was accompanied by a significant loss of
      perineuronal nets, which normally enwrap mature fast-spiking cells to limit adult
      plasticity. Accordingly, the neocortex remained plastic even beyond the peak of
      its natural critical period. These effects were not seen when redox dysregulation
      was targeted in excitatory principal cells. CONCLUSIONS: A cell-specific
      regulation of redox state thus balances plasticity and stability of cortical
      networks. Mistimed developmental trajectories of brain plasticity may underlie,
      in part, the pathophysiology of mental illness. Such prolonged developmental
      plasticity may, in turn, offer a therapeutic opportunity for cognitive
      interventions targeting brain plasticity in schizophrenia.

PMID- 25758060
TI  - The 'Parent Circle' Peace Education Program: Does it Make Any Change?
AB  - This study evaluated a peace education program facilitated by the 'parents circle
      family forum.' The program aims to expose Jewish and Palestinian-Arab adolescents
      to personal stories of bereavement as a result of the Israeli-Palestinian
      conflict. One hundred and sixty-four Jewish twelfth-grade adolescents from
      schools throughout Israel filled out questionnaires before the start of the
      educational program, and 135 Jewish adolescents filled out the same questionnaire
      up to a week after it ended. Questionnaires included empathy, anger, and
      legitimacy toward 'self' and 'others' narratives. Results indicate that, overall,
      there were not any significant differences before and after the educational
      program with regard to adolescents' attitudes toward 'self' and 'others'
      narratives. However, when examining differences between subgroups in Israeli
      society, significant differences between 'secular' and 'traditional' adolescents
      emerged. The attitudes of secular adolescents favored narratives of the 'others,'
      while the attitudes of the traditional adolescents favored the 'self' narratives.
      After the program, these differences diminished, meaning that the program had a
      different impact on each subgroup. The traditional adolescents became more
      favorable to the 'others' narratives, while the secular adolescents became more
      favorable to their own narratives. Results are discussed on the basis of the
      theoretical foundation of psychological impacts of intractable conflicts. 

PMID- 25758061
TI  - Paracetamol (acetaminophen) for patent ductus arteriosus in preterm or low-birth
      weight infants.
AB  - BACKGROUND: In preterm newborns, the ductus arteriosus frequently fails to close
      and the infants require medical or surgical closure of the patent ductus
      arteriosus (PDA). A PDA can be treated surgically or medically with one of two
      prostaglandin inhibitors, indomethacin or ibuprofen. Case reports suggest that
      paracetamol may be an alternative for the closure of a PDA. Concerns have been
      raised that in neonatal mice paracetamol may cause adverse effects on the
      developing brain, and an association between prenatal exposure to paracetamol and
      later development of autism or autism spectrum disorder has been reported.
      OBJECTIVES: To determine the efficacy and safety of intravenous or oral
      paracetamol compared with placebo or no intervention, intravenous indomethacin,
      intravenous or oral ibuprofen, or with other cyclo-oxygenase inhibitors for
      closure of a PDA in preterm or low-birth-weight infants. SEARCH METHODS: We used
      the standard search strategy of the Cochrane Neonatal Review Group. This included
      electronic searches of the Cochrane Central Register of Controlled Trials
      (CENTRAL, Cochrane Library), MEDLINE, EMBASE and CINAHL. We searched abstracts
      from the meetings of the Pediatric Academic Societies and the Perinatal Society
      of Australia and New Zealand. We searched clinicaltrials.gov; controlled
      trials.com; anzctr.org.au; World Health Organization International Clinical
      Trials Registry Platform at who.int/ictrp for ongoing trials and the Web of
      Science for articles quoting identified randomised controlled trials. We searched
      the first 200 hits on Google Scholar(TM) to identify grey literature. All
      searches were conducted in December 2013. A repeat search of MEDLINE in August
      2014 did not identify any new trials. SELECTION CRITERIA: We identified two
      randomised controlled trials (RCTs) that compared oral paracetamol to oral
      ibuprofen for the treatment of an echocardiographically diagnosed PDA in infants
      born preterm (<= 34 weeks postmenstrual age (PMA)). DATA COLLECTION AND ANALYSIS:
      We performed data collection and analyses in accordance with the methods of the
      Cochrane Neonatal Review Group. MAIN RESULTS: Two unmasked studies of treatment
      of PDA that enrolled 250 infants were included. The sequence of randomisation and
      the allocation to treatment groups were concealed in both studies. In one study
      the cardiologist assessing PDA closure was blinded to group allocation of the
      infant. In the other study it was not stated if that was the case or not. The
      quality of the trials, using GRADE, was low for the primary outcome of PDA
      closure and moderate for all other important outcomes. There was no significant
      difference between treatment with oral paracetamol versus oral ibuprofen for
      failure of ductal closure after the first course of drug administration (typical
      relative risk (RR) 0.90, 95% confidence interval (CI) 0.67 to 1.22; typical risk
      difference (RD) -0.04, 95% CI -0.16 to 0.08; I(2) = 0 % for RR and 23% for
      RD).There were no significant differences between the paracetamol and the
      ibuprofen groups in the secondary outcomes except for 'duration for need of
      supplemental oxygen' (mean difference -12 days, 95% CI -23 days to -2 days; 1
      study, n = 90) and for hyperbilirubinaemia (RR 0.57, 95% CI 0.34 to 0.97; RD 
      0.15, 95% CI -0.29 to -0.01; number needed to treat to benefit (NNTB) 7, 95% CI 3
      to 100 in favour of paracetamol; 1 study, n = 160). AUTHORS' CONCLUSIONS:
      Although a limited number of infants with a PDA have been studied in randomised
      trials of low to moderate quality according to GRADE, oral paracetamol appears to
      be as effective in closing a PDA as oral ibuprofen. In view of a recent report in
      mice of adverse effects on the developing brain from paracetamol, and another
      report of an association between prenatal paracetamol and the development of
      autism or autism spectrum disorder in childhood, long-term follow-up to at least
      18 to 24 months postnatal age must be incorporated in any studies of paracetamol
      in the newborn population. Such trials are required before any recommendations
      for the use of paracetamol in the newborn population can be made.

PMID- 25758062
TI  - Prediction of binding modes between protein L-isoaspartyl (D-aspartyl) O
      methyltransferase and peptide substrates including isomerized aspartic acid
      residues using in silico analytic methods for the substrate screening.
AB  - Because the aspartic acid (Asp) residues in proteins are occasionally isomerized
      in the human body, not only l-alpha-Asp but also l-beta-Asp, D-alpha-Asp and D
      beta-Asp are found in human proteins. In these isomerized aspartic acids, the
      proportion of D-beta-Asp is the largest and the proportions of l-beta-Asp and D
      alpha-Asp found in human proteins are comparatively small. To explain the
      proportions of aspartic acid isomers, the possibility of an enzyme able to repair
      l-beta-Asp and D-alpha-Asp is frequently considered. The protein L-isoaspartyl (D
      aspartyl) O-methyltransferase (PIMT) is considered one of the possible repair
      enzymes for l-beta-Asp and D-alpha-Asp. Human PIMT is an enzyme that recognizes
      both l-beta-Asp and D-alpha-Asp, and catalyzes the methylation of their side
      chains. In this study, the binding modes between PIMT and peptide substrates
      containing l-beta-Asp or D-alpha-Asp residues were investigated using
      computational protein-ligand docking and molecular dynamics simulations. The
      results indicate that carboxyl groups of both l-beta-Asp and D-alpha-Asp were
      recognized in similar modes by PIMT and that the C-terminal regions of substrate
      peptides were located in similar positions on PIMT for both the l-beta-Asp and D
      alpha-Asp peptides. In contrast, for peptides containing l-alpha-Asp or D-beta
      Asp residues, which are not substrates of PIMT, the computationally constructed
      binding modes between PIMT and peptides greatly differed from those between PIMT
      and substrates. In the nonsubstrate peptides, not inter- but intra-molecular
      hydrogen bonds were observed, and the conformations of peptides were more rigid
      than those of substrates. Thus, the in silico analytical methods were able to
      distinguish substrates from nonsubstrates and the computational methods are
      expected to complement experimental analytical methods.

PMID- 25758063
TI  - [Medical ethics is well established in the Undergraduate Medical Curriculum
      Vienna].

PMID- 25758064
TI  - Unique features of laterally aligned GeSi nanowires self-assembled on the vicinal
      Si (001) surface misoriented toward the [100] direction.
AB  - We demonstrate laterally aligned and catalyst-free GeSi nanowires (NWs) via self
      assembly of Ge on miscut Si (001) substrates toward the [100] direction by an
      angle theta (theta < 11 degrees ). The NWs are bordered by (001) and (105)
      facets, which are thermodynamically stable. By tuning the miscut angle theta, the
      NW height can be easily modulated with a nearly constant width. The thickness of
      the wetting layer beneath the NWs also shows a peculiar behavior with a minimum
      at around 6 degrees . An analytical model, considering the variation of both the
      surface energy and the strain energy of the epilayer on vicinal surfaces with the
      miscut angle and layer thickness, shows good overall agreement with the
      experimental results. It discloses that both the surface energy and stain energy
      of the epilayer on vicinal surfaces can be considerably affected in the same
      trend by the surface steps. Our results not only shed new light on the growth
      mechanism during heteroepitaxial growth, but also pave a prominent way to
      fabricate and meanwhile modulate laterally aligned and dislocation-free NWs. 

PMID- 25758066
TI  - Deep brain stimulation in tinnitus: current and future perspectives.
AB  - Chronic tinnitus, also known as ringing in the ears, affects up to 15% of the
      adults and causes a serious socio-economic burden. At present, there is no
      treatment available which substantially reduces the perception of this phantom
      sound. In the past few years, preclinical and clinical studies have unraveled
      central mechanisms involved in the pathophysiology of tinnitus, replacing the
      classical periphery-based hypothesis. In subcortical auditory and non-auditory
      regions, increased spontaneous activity, neuronal bursting and synchrony were
      found. When reaching the auditory cortex, these neuronal alterations become
      perceptually relevant and consequently are perceived as phantom sound. A therapy
      with a potential to counteract deeply located pathological activity is deep brain
      stimulation, which has already been demonstrated to be effective in neurological
      diseases such as Parkinson's disease. In this review, several brain targets are
      discussed as possible targets for deep brain stimulation in tinnitus. The
      potential applicability of this treatment in tinnitus is discussed with examples
      from the preclinical field and clinical case studies. 

PMID- 25758065
TI  - Chemokine receptor 7 (CCR7)-expression and IFNgamma production define vaccine
      specific canine T-cell subsets.
AB  - Canines suffer from and serve as strong translational animals models for many
      immunological disorders and infectious diseases. Routine vaccination has been a
      mainstay of protecting dogs through the stimulation of robust antibody responses
      and expansion of memory T-cell populations. Commercially available reagents and
      described techniques are limited for identifying and characterizing canine T-cell
      subsets and evaluating T-cell-specific effector function. To define reagents for
      delineating naive versus activated T-cells and identify antigen-specific T-cells,
      we tested anti-human and anti-bovine T-cell specific cell surface marker reagents
      for cross-reactivity with canine peripheral blood mononuclear cells (PBMCs. Both
      CD4(+) and CD8(+) T-cells from healthy canine donors showed reactivity to CCL19
      Ig, a CCR7 ligand, and coexpression with CD62L. An in vitro stimulation with
      concanavalin A validated downregulation of CCR7 and CD62L expression on
      stimulated healthy control PBMCs, consistent with an activated T-cell phenotype.
      Anti-IFNgamma antibodies identified antigen-specific IFNgamma-producing CD4(+)
      and CD8(+) T-cells upon in vitro vaccine antigen PBMC stimulation. PBMC isolation
      within 24h of sample collection allowed for efficienT-cell recovery and accurate
      T-cell effector function characterization. These data provide a reagent and
      techniques platform via flow cytometry for identifying canine T-cell subsets and
      characterizing circulating antigen-specific canine T-cells for potential use in
      diagnostic and field settings. 

PMID- 25758067
TI  - Elevated risk of an intermediate or high SYNTAX score in subjects with impaired
      fasting glucose.
AB  - OBJECTIVE: This study was designed to determine the SYNTAX score under different
      fasting plasma glucose (FPG) states in Chinese patients undergoing coronary
      angiography, particularly subjects with impaired FPG. METHODS: Four hundred and
      forty-six subjects undergoing coronary angiography were enrolled in this study
      and divided into four groups based on the FPG level or a history of type 2
      diabetes mellitus (T2DM): normal FPG, impaired FPG, known and previously unknown
      T2DM. RESULTS: The angiographic SYNTAX scores were higher in the subjects with
      known (p<0.001) or previously unknown (p<0.001) T2DM than in those with normal
      FPG. There were significant differences in the number of diseased coronary artery
      vessels between the subjects with known (p<0.01) or unknown T2DM (p<0.05) and the
      subjects with normal FPG. However, there were no significant differences in the
      SYNTAX score or the number of diseased coronary artery vessels between the
      subjects with impaired FPG and those with normal FPG. The subjects with impaired
      FPG (2.917-fold, p=0.004) and known (3.064-fold, p=0.000) or previously unknown
      (3.301-fold, p=0.000) T2DM exhibited a significantly elevated risk of having an
      intermediate or high SYNTAX score compared with the subjects with normal FPG.
      CONCLUSION: Chinese subjects with impaired FPG have a significantly elevated risk
      of having an intermediate or high SYNTAX score, indicating a risk of severe
      coronary artery lesions. Subjects with known or previously unknown T2DM may have
      severe coronary artery lesions. These findings suggest the importance of
      achieving better glycemic control in order to prevent coronary atherosclerosis
      and improve the cardiovascular prognosis.

PMID- 25758068
TI  - The level of bone marrow WT1 message is a useful marker to differentiate
      myelodysplastic syndromes with low blast percentage from cytopenia due to other
      reasons.
AB  - OBJECTIVE: Myelodysplastic syndromes (MDS) are a group of hematological neoplasms
      associated with ineffective hematopoiesis and that transform to acute leukemia.
      Distinguishing MDS from other cytopenias is sometimes difficult even for trained
      hematologists. WT1, the gene mutated in Wilms' tumor, was found expressed in
      acute myeloid leukemia and MDS. The amount of WT1 in peripheral blood and bone
      marrow (BM) is low in low-risk MDS subtypes, and is high in high-risk MDS
      subtypes. However, the role of WT1 in the differential diagnosis between MDS and
      other diseases showing cytopenia has not been fully addressed. The present study
      evaluated whether WT1 expression level can assist in the differential diagnosis
      of MDS from other cytopenias. METHODS: The amount of WT1 message was evaluated
      among 56 MDS patients and 47 patients with cytopenia for various other reasons
      (cytopenia VR) at the Nagasaki University Hospital. RESULTS: The level of WT1 was
      significantly related to the percentage of blasts in BM among MDS cases, and the
      type of French-American-British classification of MDS; refractory anemia (RA)
      cases showed significantly lower WT1 level than patients with RA with excess
      blasts. WT1 level was significantly related to the prognostic risk categories of
      MDS by the International Prognostic Scoring System (IPSS) and the revised IPSS.
      Although the blast percentage in the BM of RA and cytopenia VR were both less
      than 5%, there was a significant difference in the level of WT1 between MDS and
      cytopenia VR. CONCLUSION: WT1 might be a good marker to differentiate low blast
      percentage MDS and cytopenia VR.

PMID- 25758069
TI  - Association between serum haptoglobin and the pathogenesis of Alzheimer's
      disease.
AB  - OBJECTIVE: Haptoglobin (Hpg) is known to have several functional properties,
      including antioxidant and anti-inflammatory activities. In addition, it has been
      shown that the pathogenesis of neurodegenerative disorders, such as Alzheimer's
      disease (AD), involves inflammation as well as oxidative stress. However,
      evidence suggesting an association between the serum Hpg level and AD is lacking.
      Therefore, we conducted this study in order to investigate whether serum Hpg is
      associated with AD. METHODS: We compared the serum Hpg levels of 121 patients
      with newly diagnosed AD, 58 patients with Parkinson's disease (PD) and 43 healthy
      controls. We also evaluated the relationship between the severity of cognitive
      impairment in patients with AD and the serum Hpg level. RESULTS: The mean serum
      Hpg level of the patients with AD was significantly higher than that of the
      healthy controls (p=0.042), although it was not significant different from that
      observed in the PD group (p=0.613). We also found a significant positive
      association between the serum Hpg level and the severity of cognitive impairment,
      as measured using several neuropsychological tests, in the patients with AD. The
      odds ratio (95% confidence interval) of the patients with AD grouped according to
      the Hpg level was 2.417 (95% confidence interval=1.134-5.149). CONCLUSION: We
      observed a significantly higher mean serum Hpg level among the patients with AD
      compared to the healthy controls. These results support the hypothesis that
      oxidative stress and neuroinflammatory reactions play a role in the pathogenesis
      of AD.

PMID- 25758070
TI  - Potential drug interaction between warfarin and linezolid.
AB  - OBJECTIVE: Warfarin is known to interact with many drugs; however, there are
      currently no descriptions of an interaction with linezolid in the literature. It
      was recently brought to our attention, however, that several warfarin-medicated
      patients have experienced an increase in the prothrombin time international
      normalized ratio (PT-INR) following the administration of linezolid. We therefore
      performed a retrospective survey in order to investigate the possibility of an
      interaction between warfarin and linezolid. METHODS: The survey items included
      age, gender, underlying disease, type of surgery, type of infectious disease,
      duration of linezolid administration, laboratory values and the dose of warfarin.
      The PT-INR was observed over time before treatment and at days 4 or 5 and 10,
      completion and one week after the end of concomitant therapy. Patients The
      subjects included six patients who were recovering from recent heart-related
      surgery. RESULTS: The PT-INR increased from 1.62+/-0.32 before concomitant
      linezolid administration to 3.00+/-0.83 at day 4 or 5 after concomitant
      administration (p<0.01) and significantly decreased from 1.65+/-0.45 at the
      completion of the regimen to 1.26+/-0.1 one week later (p<0.05). With respect to
      the relationship between the dose of warfarin and the PT-INR in five cases, the
      PT-INR increased following concomitant linezolid treatment in all cases.
      CONCLUSION: Although it has been reported that linezolid does not influence the
      metabolism or protein binding of warfarin, our data showed potential drug
      interactions between warfarin and linezolid. Our data suggest that PT-INR
      monitoring after the completion of concomitant warfarin and linezolid therapy is
      important.

PMID- 25758071
TI  - Diagnosing latent tuberculosis in immunocompromised patients measuring blood IP
      10 production capacity: an analysis of chronic renal failure patients.
AB  - OBJECTIVE: Patients undergoing haemodialysis for chronic renal failure
      hemodialysis (CRF-HD) are at risk of latent tuberculosis infection (LTBI). The
      effectiveness of using blood IP-10 production capacity to diagnose LTBI in CRF-HD
      patients was analysed. METHODS: The study enrolled 50 CRF-HD patients. Interferon
      gamma release assay (IGRA) was done using QuantiFERON-TB Gold In Tube (QFG-IT)
      system. Blood IP-10 production capacity was measured using the QFG-IT system
      tubes. Tuberculin skin testing (TST) was performed on the same day and the test
      results were compared. RESULTS: TST turned out to be positive in 36.4% of the
      patients and QFG-IT in 54% of them. After stimulation with specific tuberculosis
      antigens, blood IP-10 levels increased noticeably. The antigen-stimulated blood
      IP-10 level was significantly higher in patients who were either TST or QFG-IT
      positive than in patients whose tests were negative (p=0.0001). Using 4.02 pg/mL
      as the threshold for stimulated blood log-transformed IP-10 level, good agreement
      was observed between IP-10 and QFG-IT results (kappa=1). CONCLUSION: Blood IP-10
      level, which can be measured simply, provides results equivalent to IGRAs for the
      diagnosis of LTBI in CRF-HD patients.

PMID- 25758072
TI  - Endoscopic incision with esophageal stenting helped to remove a gastrostomy tube
      in a patient with refractory stricture.
AB  - Most cases of esophageal benign stricture can be successfully managed with
      dilation; however, refractory stricture is often unresponsive to repeated
      dilation. Endoscopic incision is a novel technique for treating refractory
      esophageal stricture, although recurrence is noted in patients with stricture
      measuring greater than 1.5 cm, thus requiring the use of repeated incisions
      and/or preventive dilation. We herein report a case of refractory esophageal
      stricture treated with an endoscopic incision and esophageal stenting, which
      successfully allowed the gastrostomy tube to be removed. 

PMID- 25758073
TI  - Severe Cushing's syndrome related to a small pulmonary carcinoid with widespread
      dissemination.
AB  - Cushing's syndrome (CS) is characterized by the overproduction of cortisol that
      may result in significant morbidity and mortality if left untreated. CS is very
      rarely caused by ectopic adrenocorticotropic hormone production from several
      tumors, although pulmonary neuroendocrine tumors (pNETs) are the most common
      etiology. It is controversial whether such tumors are more clinically aggressive
      than other pNETs. We herein report an unusual case of severe ectopic CS caused by
      a small pulmonary carcinoid in the lung with massive neoplastic dissemination to
      the liver. We highlight and discuss the unusual clinical onset, with diagnostic
      and therapeutic criticism, of this rare entity. 

PMID- 25758074
TI  - Calcified amorphous tumor in the left atrium in a patient on long-term peritoneal
      dialysis.
AB  - A 66-year-old woman with an 11-year history of peritoneal dialysis (PD) for
      diabetic nephropathy and renal failure exhibited a movable tumor in the left
      atrium on echocardiography. Tumor resection was performed due to the difficulty
      in diagnosing the tumor and the future risk of heart failure and embolization.
      Light microscopy showed a calcified amorphous tumor (CAT), a rare intracardiac
      mass characterized by the presence of a pedicle and diffuse calcification. An
      increased calcium-phosphate product level was suspected as an etiology, although
      degeneration, inflammation and/or mineral balance disorders may also induce the
      development of CAT. We herein report the first known case of CAT in a PD patient.

PMID- 25758075
TI  - Paraganglioma-induced alveolar hemorrhage.
AB  - A 21-year-old man twice developed sudden dyspnea during running examinations for
      promotion. Chest computed tomography (CT) revealed lobular ground-glass opacity
      and centrilobular shadows bilaterally. The bronchoscopy findings were consistent
      with alveolar hemorrhage, and echocardiography showed severe hypokinesia a few
      hours later. A mass was subsequently identified along the abdominal aorta on
      enhanced CT and iodine-131 metaiodobenzylguanidine scintigraphy. Catecholamine
      oversecretion, which was later confirmed, may have increased the pulmonary vein
      pressure, thus resulting in the development of an alveolar hemorrhage, and
      damaged the cardiac muscles as manifested by hypokinesia. Since the patient had
      not previously developed alveolar hemorrhage during usual exercise, emotional
      stress superimposed on the physical activity may have triggered the paraganglioma
      to secrete excessive catecholamines, thus resulting in the observed symptoms. 

PMID- 25758076
TI  - A unique case of hot tub lung worsening during the winter.
AB  - Summer-type hypersensitivity pneumonitis includes a spectrum of granulomatous
      lung diseases that result from the inhalation of Trichosporon species in the
      summer. Hot tub lung is a granulomatous lung disease caused by the inhalation of
      water aerosols containing non-tuberculous mycobacteria. We herein describe a case
      of hot tub lung that deteriorated during the winter season. Every winter, the
      patient's symptoms, laboratory findings and chest images worsened. Genetically
      identical Mycobacterium avium strains were detected in his sputum and bathtub.
      The circulation of bathtub water during the winter months only exacerbated his
      symptoms in the winter. 

PMID- 25758077
TI  - Postobstructive pulmonary edema that developed immediately after the removal of
      an endobronchial foreign body.
AB  - The patient was a 5-year-old boy who was transported to our hospital for a
      paroxysmal cough, disturbance of consciousness, tonic-clonic convulsions and
      labored breathing. The patient's respiratory failure persisted after the
      convulsions remitted, and the presence of an endobronchial foreign body was
      suspected based on the findings of chest CT performed the following day. A peanut
      was subsequently removed from the right main bronchus using a bronchoscope with
      tracheal intubation and bag valve mask ventilation. Immediately after removal,
      the patient rapidly developed exacerbated hypoxemia, and a reduction in right
      lung lucency was noted on chest radiography. He was therefore diagnosed with type
      II postobstructive pulmonary edema, and his condition improved within a short
      period of time. 

PMID- 25758078
TI  - Primary cerebral lymphomatoid granulomatosis progressing to methotrexate
      associated lymphoproliferative disease under immunosuppressive therapy.
AB  - Lymphomatoid granulomatosis (LYG) is an angiocentric and angiodestructive
      lymphoproliferative disease involving extranodal sites. Although LYG cerebral
      lesions are usually located adjacent to LYG pulmonary lesions, few reports have
      described the occurrence of primary cerebral LYG. We herein discuss a case of a
      40-year-old Japanese woman with primary cerebral LYG that caused various
      neurological symptoms for more than five years and progressed to methotrexate
      associated lymphoproliferative disease under treatment with immunosuppressive
      therapy. This case suggests that primary cerebral LYG should be considered a
      lymphoid neoplasm manifesting as a primary brain tumor and a component of the
      differential diagnosis of chronic neuroinflammatory disorders. 

PMID- 25758079
TI  - Istradefylline is recommended for morning use: a report of 4 cases.
AB  - We herein describe four cases of patients with Parkinson's disease who were
      treated with istradefylline (ISD) in the evening and had severe daytime
      sleepiness. The time to onset of sleepiness varied between 2 weeks to 3 months.
      All patients recovered after changing the timing of the ISD dosage from evening
      to morning. ISD is an A2A receptor antagonist with a caffeine-like arousal effect
      that may worsen the quality of sleep and thus increase daytime sleepiness. This
      report provides the first evidence of daytime sleepiness induced by evening ISD
      treatment. We propose that ISD should therefore only be used in the morning,
      particularly if taken by professional drivers. 

PMID- 25758080
TI  - Cytomegalovirus polyradiculopathy in three Japanese patients with AIDS.
AB  - Polyradiculopathy (PRP) is a rare but serious neurologic complication of
      cytomegalovirus (CMV) in patients with acquired immunodeficiency syndrome (AIDS).
      We herein report three cases of CMV PRP in patients with AIDS. Although providing
      a prompt diagnosis and initiating anti-CMV therapy may achieve clinical
      improvements, administering single-drug treatment may result in virologic
      failure. Therefore, introducing antiretroviral therapy is a key step for
      improving the treatment outcomes of CMV PRP. 

PMID- 25758081
TI  - Atypical progressive multifocal leukoencephalopathy in a patient with
      antisynthetase syndrome.
AB  - Antisynthetase syndrome is a disorder belonging to the
      dermatomyositis/polymyositis group, with high rates of morbidity and mortality.
      We herein present the case of a 71-year-old man who was diagnosed with
      antisynthetase syndrome and treated with rituximab. Almost three years later, the
      patient showed right-sided hemiparesis that ultimately progressed to complete
      hemiplegia and advancing cognitive deterioration with a poor clinical outcome.
      The neuropathological diagnosis was progressive multifocal leukoencephalopathy.
      Treatment with rituximab for antisynthetase syndrome itself plays a fundamental
      role in the development of infectious complications. 

PMID- 25758082
TI  - Myopathy and eosinophilic pneumonia coincidentally induced by treatment with
      daptomycin.
AB  - A 34-year-old man with 22q11.2 deletion syndrome (DiGeorge syndrome) concurrently
      suffered from myopathy and eosinophilic pneumonia shortly after receiving
      daptomycin (DAP) for right-sided infective endocarditis. The simultaneous
      occurrence of these phenomena in relation to DAP therapy has not been previously
      well described. An allergic reaction was suspected as a possible etiology of
      these DAP-related complications. This case highlights the need for close
      observation in order to detect both musculoskeletal and respiratory disorders
      from the start of DAP therapy. Physicians should pay more attention to this new
      drug, which is expected to be frequently used in various clinical settings. 

PMID- 25758083
TI  - Thoracic aorto-esophageal fistula following endovascular aneurysm repair.

PMID- 25758084
TI  - An elderly woman with air leakage.

PMID- 25758085
TI  - Left atrial myxoma incidentally discovered on transesophageal echocardiography.

PMID- 25758086
TI  - Skin biopsy-based diagnosis of CADASIL with atypical MRI findings.

PMID- 25758087
TI  - Infarction of the abducens nucleus and facial nerve.

PMID- 25758088
TI  - Persistent Staphylococcus aureus bacteremia.

PMID- 25758089
TI  - Efficacy of direct peripheral blood smears in diagnosing necrotizing fasciitis
      caused by Streptococcus pyogenes.

PMID- 25758090
TI  - Crowned dens syndrome.

PMID- 25758091
TI  - Erratum for Fusion of the nucleoporin gene, NUP98, and the putative RNA helicase
      gene, DZXX10, by inversion 11 (p15q22) chromosome translocation in a patient with
      etoposide-related Myelodysplastic syndrome.

PMID- 25758092
TI  - A Lewis acid-free and phenolate-based magnesium electrolyte for rechargeable
      magnesium batteries.
AB  - A novel Lewis acid-free and phenolate-based magnesium electrolyte has been
      established. The excellent reversibility and stability of this electrolyte in
      battery cycling render this novel Lewis acid-free synthetic approach as a highly
      promising alternative for the development of highly anodically stable magnesium
      electrolytes for rechargeable magnesium batteries. 

PMID- 25758093
TI  - Constipation in children: fibre and probiotics.
AB  - INTRODUCTION: Prevalence of childhood constipation has been estimated at 1% to
      30% in the general population worldwide; most children have no obvious
      aetiological factors. One third of children with chronic constipation continue to
      have problems beyond puberty. Half of the children with chronic faecal impaction
      and faecal incontinence have experienced an episode of painful defecation, and
      many children with chronic constipation exhibit withholding behaviour. METHODS
      AND OUTCOMES: We conducted a systematic review and aimed to answer the following
      clinical questions: What are the effects of fibre for children with chronic
      constipation? What are the effects of probiotics for children with chronic
      constipation? 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 12 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: fibre
      and probiotics.

PMID- 25758094
TI  - Application of data mining tools for classification of protein structural class
      from residue based averaged NMR chemical shifts.
AB  - The number of protein sequences deriving from genome sequencing projects is
      outpacing our knowledge about the function of these proteins. With the gap
      between experimentally characterized and uncharacterized proteins continuing to
      widen, it is necessary to develop new computational methods and tools for protein
      structural information that is directly related to function. Nuclear magnetic
      resonance (NMR) provides powerful means to determine three-dimensional structures
      of proteins in the solution state. However, translation of the NMR spectral
      parameters to even low-resolution structural information such as protein class
      requires multiple time consuming steps. In this paper, we present an unorthodox
      method to predict the protein structural class directly by using the residue's
      averaged chemical shifts (ACS) based on machine learning algorithms. Experimental
      chemical shift information from 1491 proteins obtained from Biological Magnetic
      Resonance Bank (BMRB) and their respective protein structural classes derived
      from structural classification of proteins (SCOP) were used to construct a data
      set with 119 attributes and 5 different classes. Twenty four different
      classification schemes were evaluated using several performance measures. Overall
      the residue based ACS values can predict the protein structural classes with 80%
      accuracy measured by Matthew correlation coefficient. Specifically protein
      classes defined by mixed alphabeta or small proteins are classified with >90%
      correlation. Our results indicate that this NMR-based method can be utilized as a
      low-resolution tool for protein structural class identification without any prior
      chemical shift assignments. 

PMID- 25758095
TI  - Hodgkin lymphoma risk following infectious and chronic inflammatory diseases: a
      large population-based case-control study from Sweden.
AB  - Patients with Hodgkin lymphoma (HL) have a well-characterized immune deficiency
      of T cell function, originally identified by increased susceptibility to certain
      infections. Epidemiological evidence has long pointed to infectious etiologies in
      younger HL patients. With the aim of expanding our knowledge on the potential
      role of pre-existing immune deficiency in HL and an infectious/inflammatory
      etiology, we conducted a comprehensive population-based case-control study in HL
      patients diagnosed in Sweden in the period 1965-2004, and their matched controls.
      In a large population-based study including 7,414 HL patients and 29,240 matched
      controls, we evaluated the subsequent risk of HL in relation to a broad range of
      infectious and inflammatory conditions, using unconditional logistic regression.
      A previous history of any reported infection was associated with an 11 %
      increased risk of HL (P < 0.05). More specifically, we found sinusitis (odds
      ratio = 1.81; 95 % confidence interval = 1.06-3.07), tuberculosis (1.76; 1.01
      3.07), encephalitis (7.88; 1.97-31.5), and herpes zoster (2.20; 1.11-4.35) to be
      associated with excess HL risk. A personal prior history of chronic inflammatory
      condition was not associated with an increased risk of HL (0.94; 0.71-1.14). Our
      results suggest that underlying immune deficiency is a primary phenomenon in HL.
      Alternatively, certain infectious agents may be potential HL triggers.

PMID- 25758096
TI  - The mechanism of synergistic effects of arsenic trioxide and rapamycin in acute
      myeloid leukemia cell lines lacking typical t(15;17) translocation.
AB  - Arsenic trioxide (ATO) has potent clinical activity in the treatment of patients
      with acute promyelocytic leukemia (APL), but is much less efficacious in acute
      myeloid leukemia (AML) lacking t(15;17) translocation. Recent studies have
      indicated that the addition of mammalian target of rapamycin (mTOR) inhibitors
      may increase the sensitivity of malignant cells to ATO. The aim of the present
      study was to test for possible synergistic effects of ATO and rapamycin at
      therapeutically achievable doses in non-APL AML cells. In HL-60 and U937 cell
      lines, the inhibitory effects of low concentrations of ATO and rapamycin were
      synergistic and more pronounced in U937 cells. The combination of drugs increased
      apoptosis in HL-60 cells and increased the percentage of cells in G(0)/G(1) phase
      in both cell lines. In U937 cells, rapamycin alone increased the activity of
      mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK)
      and the addition of ATO decreased the level of phosphorylated ERK, Ser473
      phosphorylated Akt and anti-apoptotic Mcl-1 protein. Primary AML cells show high
      sensitivity to growth-inhibitory effects of rapamycin alone or in combination
      with ATO. The results of the present study reveal the mechanism of the
      synergistic effects of two drugs at therapeutically achievable doses in non-APL
      AML cells.

PMID- 25758097
TI  - Efficacy of myeloablative allogeneic hematopoietic stem cell transplantation in
      adult patients with MLL-ELL-positive acute myeloid leukemia.
AB  - Acute myeloid leukemia (AML) with mixed lineage leukemia-eleven-nineteen lysine
      rich leukemia (MLL-ELL) is a rare subtype of MLL-rearranged AML. The outcome of
      allogeneic hematopoietic stem cell transplantation (allo-HSCT) for patients with
      this disease remains unknown. In the present study, we retrospectively
      investigated the efficacy of allo-HSCT in eight adult MLL-ELL-positive AML
      patients. Although all eight patients achieved first complete remission (CR1),
      three (37.5 %) patients experienced relapse after induction therapy. Five (62.5
      %) patients underwent allo-HSCT during CR1, whereas two (25.0 %) underwent allo
      HSCT during disease relapse, and one (12.5 %) during CR2. All three patients who
      received allo-HSCT beyond CR1 died due to AML progression after allo-HSCT. Of the
      five patients who received allo-HSCT during CR1, three (60.0 %) remained alive at
      study conclusion. The overall survival rate at five years was 50.0 %.
      Intriguingly, clonally expanded non-leukemic cells expressing MLL-ELL during
      consolidation therapy were found to be eradicated after allo-HSCT during the
      monitoring of minimal residual disease in one patient; this indicates that allo
      HSCT is efficacious for eliminating pre-leukemic cells resistant to chemotherapy.
      In conclusion, allo-HSCT soon after CR1 represents a promising therapeutic option
      for adult AML patients with MLL-ELL, although the outcome of allo-HSCT for
      patients beyond CR1 was dismal.

PMID- 25758098
TI  - Mouse hallucal metatarsal cross-sectional geometry in a simulated fine branch
      niche.
AB  - Mice raised in experimental habitats containing an artificial network of narrow
      "arboreal" supports frequently use hallucal grasps during locomotion. Therefore,
      mice in these experiments can be used to model a rudimentary form of arboreal
      locomotion in an animal without other morphological specializations for using a
      fine branch niche. This model would prove useful to better understand the origins
      of arboreal behaviors in mammals like primates. In this study, we examined if
      locomotion on these substrates influences the mid-diaphyseal cross-sectional
      geometry of mouse metatarsals. Thirty CD-1/ICR mice were raised in either
      arboreal (composed of elevated narrow branches of varying orientation) or
      terrestrial (flat ramps and walkways that are stratified) habitats from weaning
      (21 days) to adulthood (>=4 months). After experiments, the hallucal metatarsal
      (Mt1) and third metatarsal (Mt3) for each individual were isolated and micro
      computed tomography (micro-CT) scans were obtained to calculate mid-shaft cross
      sectional area and polar section modulus. Arboreal mice had Mt1s that were
      significantly more robust. Mt3 cross sections were not significantly different
      between groups. The arboreal group also exhibited a significantly greater Mt1/Mt3
      ratio for both robusticity measures. We conclude that the hallucal metatarsal
      exhibits significant phenotypic plasticity in response to arboreal treatment due
      to habitual locomotion that uses a rudimentary hallucal grasp. Our results
      support the hypothesis that early adaptive stages of fine branch arboreality
      should be accompanied by a slightly more robust hallux associated with the
      biomechanical demands of this niche.

PMID- 25758099
TI  - Patterns of linkage disequilibrium at PARK16 may explain variances in genetic
      association studies.
AB  - BACKGROUND: Reproducing genomewide association studies findings in different
      populations is challenging, because the reproducibility fundamentally relies on
      the similar patterns of linkage disequilibrium between the unknown causal
      variants and the genotyped single-nucleotide polymorphisms (SNPs). METHODS: The
      PARK16 locus was reported to alter the risk of Parkinson's disease (PD) in
      genomewide association studies in Japanese and Caucasians. We evaluated the
      regional linkage disequilibrium pattern at PARK16 locus in Caucasians, Japanese,
      and Chinese from HapMap and Chinese, Malays, and Indians from the Singapore
      Genome Variation Project, using the traditional heatmaps and targeted analysis of
      PARK16 gene via Monte Carlo simulation through varLD scores of these ethnic
      groups. RESULTS: One hundred SNPs in Caucasians, 95 SNPs in Chinese, 78 SNPs in
      Japanese from HapMap, 86 SNPs in Chinese, 99 SNPs in Indians, and 97 SNPs in
      Malays from the Singapore Genome Variation Project were included. Our targeted
      analysis showed that the linkage disequilibrium pattern of SNPs close to rs947211
      was similar in Caucasians and Asians, including Chinese, Japanese, and Malay (all
      P > 0.0001), whereas different linkage disequilibrium patterns around rs823128,
      rs823156, and rs708730 were found between Caucasians and these Asian groups (all
      P < 0.0001). CONCLUSIONS: Our study suggests a higher chance to detect the
      association between rs947211 and PD in Chinese, Malay, and other Caucasian groups
      because of the similar linkage disequilibrium pattern around rs947211. The
      associations between rs823128/rs823156/rs708730 and PD are more likely to be
      replicated in Chinese and Malay populations.

PMID- 25758101
TI  - Should all patients have ambulatory blood pressure monitoring performed to
      validate the diagnosis of hypertension?

PMID- 25758100
TI  - Esthetic, clinical and patient-centered outcomes of immediately placed implants
      (Type 1) and early placed implants (Type 2): preliminary 3-month results of an
      ongoing randomized controlled clinical trial.
AB  - AIM: The objective of the study was to compare (i) esthetic, (ii) clinical and
      (iii) patient-centered outcomes following immediate (Type 1) and early implant
      placement (Type 2). MATERIAL AND METHODS: Thirty-eight subjects needing a single
      extraction (premolar to premolar) were randomly allocated to Type 1 or Type 2
      implant placement. Three months following permanent crown insertion, evaluation
      of (i) esthetic outcomes using soft tissue positions, and the pink and white
      esthetic scores (PES/WES), (ii) clinical performance using probing pocket depth
      (PPD), modified plaque index (mPI) and modified sulcus bleeding index (mSBI)
      around each implant and (iii) patient satisfaction by means of a questionnaire
      using a visual analogue scale (VAS) was performed. RESULTS: Thirty-two patients
      completed the 3-month follow-up examination (Type 1, n = 17; Type 2, n = 15) with
      a 100% implant survival rate. Type 1 implants lost 0.54 +/- 0.18 mm of mid-facial
      soft tissue height, while Type 2 implants lost 0.47 +/- 0.31 mm (P > 0.05). The
      papillae height on the mesial and distal was reduced about 1 mm following both
      procedures. The PES/WES following Type 1 implant placement amounted to 13.7 +/-
      0.6 and 12.5 +/- 0.7 in the Type 2 group (P > 0.05). PPD, mPI and mSBI were low
      in both groups (P > 0.05). Patient-centered outcomes failed to demonstrate any
      statistical difference between the two cohorts. CONCLUSION: Three months
      following final crown delivery, there were no significant differences in
      esthetic, clinical and patient-centered outcomes following Type 1 and Type 2
      implant placement. On the short term, one may achieve good optimal esthetic and
      clinical results irrespective of these two placement protocols. These results
      need to be confirmed on the long term.

PMID- 25758102
TI  - Spontaneous acquisition of infinite proliferative capacity by a rabbit corneal
      endothelial cell line with maintenance of phenotypic and physiological
      characteristics.
AB  - Rabbit cells and models are frequently used in pharmacological experiments and
      toxicity tests and are particularly useful for corneal transplant experiments.
      Here, we obtained a corneal endothelial cell line from normal rabbit corneal
      endothelium that had acquired infinite proliferative potential without requiring
      gene transfer. These infinitely proliferative rabbit corneal endothelial cells
      (iRCECs) could be cultured for > 250 generations and exhibited a greater ability
      to proliferate than did normal rabbit corneal endothelial cells (RCECs)
      cultivated by conventional methods. The results of reverse transcriptase
      polymerase chain reaction (RT-PCR) and immunostaining analyses revealed that the
      expression profiles of corneal endothelial markers, such as collagen type
      VIIIalpha1 and Na+ /K+ -ATPase, were similar to those of RCECs and in vivo
      corneal endothelium. Scanning electron microscopy showed that many microvilli
      were present on the surface of the cells and that the ultrastructure was
      maintained. In addition, we verified that the iRCECs had similar levels of pump
      function as did RCECs using an Ussing chamber system. The results of a soft agar
      colony-formation assay suggested that the iRCECs were not tumourigenic. Taken
      together, our results demonstrated that the iRCECs exhibited gene expression
      profiles and properties that were equivalent to those of native rabbit corneal
      endothelium, making these cells useful for corneal endothelial research studies.
      Copyright (c) 2015 John Wiley & Sons, Ltd.

PMID- 25758103
TI  - Do existing patient-report activity outcome measures accurately reflect day-to
      day arm use following adult traumatic brachial plexus injury?
AB  - OBJECTIVE: To identify the range of activities limited following adult traumatic
      brachial plexus injury and triangulate these with existing patient-reported
      outcome measures identified from the literature. DESIGN: A qualitative cross
      sectional design. SUBJECTS: Adults with traumatic brachial plexus injury and
      expert clinicians. METHODS: Using an International Classification of Functioning,
      Disability and Health (ICF) framework, participants identified day-to-day
      activities that are limited following traumatic brachial plexus injury. Two
      independent reviewers classified all reported activities into the Comprehensive
      ICF Core Set of Hand Conditions (CCS-HC) activity domains. Reported activities
      were triangulated with patient-reported outcome measures identified from the
      brachial plexus injury literature. RESULTS: Fifty-one participants (21 adults
      with brachial plexus injury, 30 expert clinicians) generated a total of 522
      items. The inter-rater reliability for classification to CCS-HC domains was
      excellent (k = 0.94, 95% confidence interval (95% CI) 0.92-0.96). Activities
      reported by patients and clinicians represented all 29 CCS-CH activity domains.
      Five activities (2%) could not be classified to any ICF domain. Fifteen CCS-HC
      activity domains were represented in the Disabilities of Arm, Shoulder and Hand
      (DASH) and ABILHAND, 2 measures currently used in the brachial plexus injury
      literature. CONCLUSION: Adults with a brachial plexus injury report a range of
      activities that are limited following injury, and are under-represented in
      currently used patient-reported outcome measures. The activities reported in this
      study could be used to inform the development of a new brachial plexus injury
      targeted questionnaire.

PMID- 25758105
TI  - [Molecular pathology].

PMID- 25758104
TI  - Prevention of exercised induced cardiomyopathy following Pip-PMO treatment in
      dystrophic mdx mice.
AB  - Duchenne muscular dystrophy (DMD) is a fatal neuromuscular disorder caused by
      mutations in the Dmd gene. In addition to skeletal muscle wasting, DMD patients
      develop cardiomyopathy, which significantly contributes to mortality. Antisense
      oligonucleotides (AOs) are a promising DMD therapy, restoring functional
      dystrophin protein by exon skipping. However, a major limitation with current AOs
      is the absence of dystrophin correction in heart. Pip peptide-AOs demonstrate
      high activity in cardiac muscle. To determine their therapeutic value, dystrophic
      mdx mice were subject to forced exercise to model the DMD cardiac phenotype.
      Repeated peptide-AO treatments resulted in high levels of cardiac dystrophin
      protein, which prevented the exercised induced progression of cardiomyopathy,
      normalising heart size as well as stabilising other cardiac parameters. Treated
      mice also exhibited significantly reduced cardiac fibrosis and improved
      sarcolemmal integrity. This work demonstrates that high levels of cardiac
      dystrophin restored by Pip peptide-AOs prevents further deterioration of
      cardiomyopathy and pathology following exercise in dystrophic DMD mice. 

PMID- 25758106
TI  - beta-Alanine supplemented diets enhance behavioral resilience to stress exposure
      in an animal model of PTSD.
AB  - This study investigated the effects of beta-alanine (BA) ingestion on the
      behavioral and neuroendocrine response of post-traumatic stress disorder (PTSD)
      in a murine model. Animals were fed a normal diet with or without (PL) BA
      supplementation (100 mg kg(-1)) for 30 days. Animals were then exposed to a
      predator-scent stress (PSS) or a sham (UNEX). Behaviors were evaluated using an
      elevated plus maze (EPM) and acoustic startle response (ASR) 7 days following
      exposure to the PSS. Corticosterone concentrations (CS), expression of brain
      derived neurotrophic factor (BDNF), and brain carnosine concentrations were
      analyzed a day later. Animals in PSS+PL spent significantly less time in the open
      arms and in the number of entries in the EPM than PSS+BA, UNEX+BA, or UNEX+PL.
      Animals in PSS+BA had comparable scores to UNEX+BA. Anxiety index was higher (p <
      0.05) in PSS+PL compared to PSS+BA or animals that were unexposed. ASR and
      freezing were greater (p < 0.05) in animals exposed to PSS compared to animals
      unexposed. CS expression was higher (p < 0.05) in animals exposed to PSS compared
      to unexposed animals. Brain carnosine concentrations in the hippocampus and other
      brain sections were significantly greater in animals supplemented with BA
      compared to PL. BDNF expression in the CA1 and DG subregions of the hippocampus
      was lower (p < 0.05) in animals exposed and fed a normal diet compared to animals
      exposed and supplemented with BA, or animals unexposed. In conclusion, BA
      supplementation in rats increased brain carnosine concentrations and resulted in
      a reduction in PTSD-like behavior, which may be mediated in part by maintaining
      BDNF expression in the hippocampus.

PMID- 25758107
TI  - [Prevalence of gastrointestinal disorders in adults with common variable
      immunodeficiency at Specialty Hospital Dr. Bernardo Sepulveda].
AB  - BACKGROUND: The common variable immunodeficiency (CVID) shows a variable
      incidence, from 1:15,000 to 1:117,000, without gender predominance. The incidence
      of gastrointestinal manifestations in these patients ranges from 20-60%, and
      these may be the first and only clinical manifestation of CVID, while other
      patients develop gastrointestinal complications during the course of it. In
      Mexico there is little information regarding the type and frequency of
      gastrointestinal disorders presented by adult patients with CVID. OBJECTIVE: To
      determine the prevalence of gastrointestinal manifestations in adult patients
      with CVID. MATERIAL AND METHOD: A descriptive, cross-sectional and observational
      study was made including patients with CVID attending Primary Immunodeficiency
      Clinic of Allergy and Clinical Immunology Department, Specialties Hospital,
      National Medical Center SXXI, Mexico City. All patients underwent
      gastrointestinal symptoms questionnaire, laboratory, cabinet, endoscopy and
      breath test for bacterial overgrowth. RESULTS: We evaluated 17 patients, 8 men
      and 9 women with an average age of 36 years with a definitive diagnosis of CVID
      according to international criteria; 59% had abdominal pain, 53% abdominal
      distension; only 3 patients (17.6%) reported constipation; 47% had chronic
      diarrhea, of which only 2 (11.8%) had rectal pushing. The diagnoses of
      gastrointestinal manifestations of this population were: 18% chronic diarrhea,
      celiac disease and bacterial overgrowth, 24% gastrointestinal functional
      disorder, 12% constipation and 6% dyspepsia. One patient (6%) had no
      gastrointestinal symptoms. CONCLUSIONS: Prevalence of gastrointestinal diseases
      in adult patients with common variable immunodeficiency was 94%. There was no
      gender predominance. It is therefore important that patients with CVID will
      conduct a study protocol that includes a complete medical history considering
      gastrointestinal symptoms and signs, in order to determine timely diagnosis and
      therapeutic approach.

PMID- 25758108
TI  - [Aerobiological study of anemophilous pollens in the city of Toluca, Mexico].
AB  - BACKGROUND: Due to the high incidence of allergic diseases in Mexico, caused by
      exposure to pollens, there have been several studies of plants and atmospheric
      pollens in various regions in the last decades. In the city of Toluca there have
      been two previous pollen samplings using gravimetric methodology, for which it is
      necessary to obtain new samplings with a standardized volumetric technique, in
      order to have updated and confident results of a region with considerable
      environmental changes in the last years. OBJECTIVE: To determine the different
      types of pollens, seasonal variations and behavior in the four seasons of the
      year. MATERIAL AND METHOD: A descriptive study, related to the identification of
      pollens by the suction and trapping of particles with the volumetric sampler type
      Hirst (Burkard) performed in the city of Toluca, Mexico, from October 1, 2004 to
      September 30, 2005. RESULTS: Twenty-nine different airborne pollen types were
      identified, which amounted a total of 13,542 pollen grains. During winter we
      found the largest number of pollens. The months with the highest and lowest
      amount of pollens were January and August, respectively. Pollens from trees
      predominated, mainly from the Cupressaceae (44%) and Pinaceae (13.8%) families,
      which were present in the atmosphere throughout the year. CONCLUSIONS: We
      identified a larger amount of pollens from trees in winter, mainly from the
      Cupressaceae family, and it is closely related to the number of trees planted of
      this species in the city.

PMID- 25758109
TI  - [Prevalence, location and tomographic severity of chronic rhinosinusitis in adult
      patients with common variable immunodeficiency].
AB  - BACKGROUND: Common variable immunodeficiency (CVID) is one of the most common
      antibody deficiencies in adults. The prevalence of respiratory infections have
      been reported in 75% vs 2-16% in general population. Chronic rhinosinusitis is an
      inflammatory disease affecting paranasal sinuses and nose. OBJECTIVE: To show the
      prevalence of chronic rhinosinusitis, affected sinus and severity by CT scan in
      adult patients with CVID. MATERIAL AND METHOD: A descriptive, observational and
      cross sectional study was made including 21 patients with CVID. Paranasal sinus
      CT scan was performed to all patients and was assessed by Otolaryngologist. The
      chronic rhinosinusitis severity was assessed with Lund-Mackay score. RESULTS: Out
      of 21 patients, 15 were women (71.5%); average age was of 40 years (+/-13), 12
      patients had chronic rhinosinusitis; according to Lund-Mackay score, 2 (17.8%)
      had the severe form, 3 (7.7%) had the moderate and 7 (54.5%) the mild one. The
      most affected sinus was bilateral maxilar sinus (n=7, 33%), ethmoid (n=6, 26%),
      unilateral maxilar sinus (n=4, 19%), frontal and sphenoid (n=3, 13%) each one.
      The following anatomical variations were found: deviated septum (n=6, 28.5%),
      maxillary septum (n=3, 14.2%), bilateral maxillary sinus hypoplasia (n=2, 10%),
      unilateral concha bullosa (n=2, 10%) and pneumatized Agger Nasi cell (n=1, 4.7%).
      CONCLUSIONS: 52% of patients with common variable immunodeficiency (CVID)
      presented chronic rhinosinusitis, 58% mild according to Lund-Mackay score; the
      main affected sinus was bilateral maxillary sinus (33%). Due to the prevalence of
      chronic rhinosinusitis in patients with common variable immunodeficiency,
      paranasal sinus CT scan should be performed in all patients to establish
      diagnosis and treatment.

PMID- 25758110
TI  - [Malignancies in adult patients with common variable immunodeficiency].
AB  - BACKGROUND: Common variable immunodeficiency (CVID) implies an increased risk of
      cancer, with an estimated incidence of 11-13%, particularly during the 5th and
      6th decade of life. B cell-Hodgkin lymphomas are the more frequent cancer,
      followed by non-Hodgkin lymphoma and epithelial tumors (gastric, breast, bladder
      and cervix). OBJECTIVE: To describe the types of cancers in a cohort of adult
      patients with CVID. MATERIAL AND METHOD: An observational, cross-sectional and
      descriptive study was made in which we reviewed the charts of patients with CVID
      attending the Primary Immunodeficiencies Clinic at Specialties Hospital Dr.
      Bernardo Sepulveda, Centro Medico Nacional Siglo XXI, Mexico City. RESULTS: There
      were included 23 patients with CVID diagnosis, 13 women (56%) and 10 men (44%),
      with an average age of 36.7 years. Four patients developed malignancies (2 men
      and 2 women), with a prevalence of 17.3%. The types of cancers in this group of
      patients were: B cell-Hodgkin lymphoma (1/23), neuroendocrine carcinoma of the
      pancreas (1/23), myeloid chronic leukemia (1/23) and thyroid papillary carcinoma
      (1/23). In two of the subjects the diagnosis of cancer was established previous
      to CVID diagnosis. The average age of diagnosis of cancer was 27 years (19-34
      years). CONCLUSIONS: In our patients we found different types of malignancies
      compared to previously described. We consider necessary a screening protocol for
      an early diagnosis of cancer in these patients. The frequency of cancer in our
      population was the same as reported in the literature.

PMID- 25758111
TI  - [Clinical-epidemiological profile of patients with suspicion of alimentary
      allergy in Mexico. Mexipreval Study].
AB  - BACKGROUND: Adverse reaction to food has increased around the world in last
      years. Prevalence of food allergy raises between 2-4% in adults, and 6-8% in
      children. The clinical presentation is heterogeneous and varies from mild
      symptoms to anaphylactic reactions. Even the clinical history focused in the food
      is important; demonstration of allergen sensitization is mandatory. OBJECTIVE: To
      describe the profile of the patients with suspicion of food allergy and the
      regular clinical practice followed in Mexico. MATERIAL AND METHOD: An
      observational, descriptive, cross-sectional study was carried out from March 2013
      to March 2014 using a convenience sample of allergic patients who were treated in
      the office, both private and public, of those physicians who seen food allergy
      patients. RESULTS: Clinical, epidemiological, diagnostic and therapeutic data
      were collected from 1,971 suspicious food allergic patients presenting for the
      first time in the departments of the researchers involved in the study. No
      difference was found in relation to gender. In relation to age, a bimodal
      distribution, with peaks at 2 and 35 years old, was found. A history of
      respiratory allergy was present in 75% of cases; 80% of patients had had any
      previous symptoms before seeking consultation and the most frequent clinical
      manifestations were cutaneous, 5% reported anaphylaxis. CONCLUSION: The foods
      involved in reactions change with age. The clinical presentation changes with the
      food, although the skin is the most frequently affected organ. Even if the
      suspicious were high, the confirmation with specific diagnostic tools is strongly
      recommended.

PMID- 25758112
TI  - [Prevalence of sensitization to cow's milk and egg among patients with suspicion
      of IgE mediated diseases].
AB  - BACKGROUND: In Latin America, there are very few epidemiological data on food
      allergy and sensitization to milk and egg. OBJECTIVE: To describe the frequency
      of sensitization to milk and egg in a population with suspicion of IgE mediated
      diseases. MATERIAL AND METHOD: A retrospective and descriptive study was made
      with patients who consulted to our service of Allergy, with suspicion of
      exacerbation of possible IgE mediated diseases when eat certain foods. All
      patients had skin prick test including the suspected foods and milk and egg. Each
      patient had a complete clinical history. RESULTS: Sensitization to at less one
      food was present in 29.7% of patients. Egg sensitization occurred in 6.1% of
      patients and it was associated with asthma, rhinitis and gastrointestinal
      eosinophilia in children younger than five years. Milk sensitization was present
      in 4.5% and was not associated with any disease. CONCLUSIONS: In Colombia,
      sensitization to milk and egg is relatively low compared to that reported in
      other studies with population with high risk of sensitization. Because of the
      association between sensitization of egg and the risk of having respiratory
      symptoms and gastrointestinal eosinophilia, an egg sensitization could be and
      early marker of poor prognosis in atopic patients.

PMID- 25758113
TI  - [Occupational asthma].
AB  - The occupational asthma is the most common form of lung disease caused by factors
      that are attributed to a specific working environment in industrialized
      countries. It causes variable limitation of airflow and/or hyper-responsiveness
      of the airway due to contact with specific agents present in an atmosphere of
      work and not to stimuli found out of this place. It is recognized more and more
      frequently, and many agents are capable of causing occupational asthma by
      different pathophysiological mechanisms. More than 400 agents causing
      occupational asthma are known and every year new triggers are detected. Numerous
      factors contribute to the pathogenesis of occupational asthma induced chemically,
      including immunological, non-immunological mechanisms of epithelial damage,
      airway remodeling, oxidative stress, neurogenic inflammation as well as genetic
      factors. The most important risk factors for occupational asthma include: atopy,
      smoking and genetic factors. The diagnosis is based on the clinical history, skin
      tests, immunological tests and functional studies. The fundamental treatment is
      removing the worker from exposure as soon as possible. The advance in the
      knowledge of the pathogenesis of occupational asthma will importantly influence
      in the prevention and the management of this disease. 

PMID- 25758114
TI  - [Mastocytosis].
AB  - Mastocytosis is one of the eight subcategories of the myeloproliferative
      neoplasms of the classification of lymphoid and hematopoietic tissues' tumors of
      2008 of World Health Organization; it is an heterogeneous group of
      myeloproliferative diseases characterized by the excessive proliferation of
      atypical mastocytes in morphological and immunophenotype terms, besides the
      cumulus of these cells in one or several organs or tissues, including skin, bone
      marrow, liver, spleen and lymph nodes. 

PMID- 25758115
TI  - [Infection due to Mycobacterium bovis in common variable immunodeficiency].
AB  - Common variable immunodeficiency (CVID) is an heterogeneous group of disorders
      characterized by impaired antibody production. It shows a wide spectrum of
      manifestations including severe and recurrent respiratory infections
      (Streptococcus pneumoniae, Haemophilus) and gastrointestinal (Campylobacter
      jejuni, rotavirus and Giardia lamblia). Viral infections caused by herpes zoster,
      cytomegalovirus (CMV) and hepatitis C are rare. The opportunistic agents such as
      CMV, Pneumocystis jirovecii, cryptococcus and atypical mycobacteria have been
      reported as isolated cases. This paper reports the case of a 38-year-old female
      patient, who began six years before with weight loss of 7 kg in six months,
      fatigue, weakness, sweating, fever and abdominal pain. Furthermore, patient had
      intestinal obstruction and abdominal CT showed mesenteric lymph growth. The
      mesenteric lymph node biopsy revealed positives Mycobacterium PCR, Ziehl-Neelsen
      staining and culture for M. bovis. In the laparotomy postoperative period was
      complicated with nosocomial pneumonia, requiring mechanical ventilation and
      tracheostomy. Two years later, she developed right renal abscess that required
      surgical drainage, once again with a positive culture for Mycobacterium bovis.
      She was referred to highly specialized hospital and we documented
      panhypogammaglobulinemia and lymphopenia. Secondary causes of
      hypogammaglobulinemia were ruled out and common variable immunodeficiency (CVID)
      was confirmed, we started IVIG replacement. Four years later she developed mixed
      cellularity Hodgkin's lymphoma. Until today she continues with IVIG and
      chemotherapy. This report of a patient with CVID and Mycobacterium bovis
      infection, a unusual association, shows the cellular immunity susceptibility in
      this immunodeficiency, additional to the humoral defect. 

PMID- 25758116
TI  - [Hypersensitivity to mosquito bite manifested as Skeeter sindrome].
AB  - The reactions to mosquito bites are immunological reactions with involvement of
      IgE, IgG and T cells mediated hypersensitivity. These reactions are common and
      range from small local reactions, large local reactions to systemic allergic
      reactions. Skeeter syndrome is defined as a large local induced inflammatory
      reaction to mosquito bite and sometimes accompanied by systemic symptoms such as
      fever and vomiting. Diagnosis is based on clinical history and physical
      examination, supported by the identification of specific IgE by skin testing.
      Treatment includes prevention, antihistamines and steroids in some cases.
      Specific immunotherapy still requires further study. This paper reports two cases
      of patients with hypersensitivity reactions to mosquito bites, which were
      evaluated in our center presenting positive skin tests. 

PMID- 25758120
TI  - Does household use of biomass fuel cause lung cancer? A systematic review and
      evaluation of the evidence for the GBD 2010 study.
AB  - BACKGROUND: Around 2.4 billion people use traditional biomass fuels for household
      cooking or heating. In 2006, the International Agency for Research on Cancer
      (IARC) concluded emissions from household coal combustion are a Group 1
      carcinogen, while those from biomass were categorised as 2A due to epidemiologic
      limitations. This review updates the epidemiologic evidence and provides risk
      estimates for the 2010 Global Burden of Disease study. METHODS: Searches were
      conducted of 10 databases to July 2012 for studies of clinically diagnosed or
      pathologically confirmed lung cancer associated with household biomass use for
      cooking and/or heating. FINDINGS: Fourteen eligible studies of biomass cooking or
      heating were identified: 13 had independent estimates (12 cooking only), all were
      case-control designs and provided 8221 cases and 11 342 controls. The ORs for
      lung cancer risk with biomass for cooking and/or heating were OR 1.17 (95% CI
      1.01 to 1.37) overall, and 1.15 (95% CI 0.97 to 1.37) for cooking only.
      Publication bias was not detected, but more than half the studies did not
      explicitly describe a clean reference category. Sensitivity analyses restricted
      to studies with adequate adjustment and a clean reference category found ORs of
      1.21 (95% CI 1.05 to 1.39) for men (two reports, compiling five studies) and 1.95
      (95% CI 1.16 to 3.27) for women (five reports, compiling eight studies). Exposure
      response evidence was seen for men, and higher risk for women in developing
      compared with developed countries, consistent with higher exposures in the
      former. CONCLUSIONS: There is now stronger evidence for biomass fuel use causing
      lung cancer, but future studies need better exposure assessment to strengthen
      exposure-response evidence.

PMID- 25758121
TI  - Acute respiratory distress syndrome or pulmonary oedema?

PMID- 25758122
TI  - The effect of nanoparticle permeation on the bulk rheological properties of mucus
      from the small intestine.
AB  - The effectiveness of delivering oral therapeutic peptides, proteins and
      nucleotides is often hindered by the protective mucus barrier that covers mucosal
      surfaces of the gastrointestinal (GI) tract. Encapsulation of active
      pharmaceutical ingredients (API) in nanocarriers is a potential strategy to
      protect the cargo but they still have to pass the mucus barrier. Decorating
      nanoparticles with proteolytic enzymes has been shown to increase the permeation
      through mucus. Here we investigate the effect of poly(acrylic acid) (PAA)
      nanoparticles decorated with bromelain (BRO), a proteolytic enzyme from pineapple
      stem, on the bulk rheology of mucus as well as non-decorated poly(lactic-co
      glycolic acid) (PLGA) nanoparticles. Porcine intestinal mucus from the small
      intestine was incubated for 30min in the presence of PLGA nanoparticles or
      polyacrylic nanoparticles decorated with bromelain (PAA-BRO). The effect of
      nanoparticles on the rheological properties, weight of gel, released glycoprotein
      content from mucus as well as the viscosity of liquid removed was assessed.
      Treatment with nanoparticles decreased mucus gel strength with PAA-BRO reducing
      it the most. PAA-BRO nanoparticles resulted in the release of increased
      glycoprotein from the gel network whereas mucus remained a gel and exhibited a
      similar breakdown stress to control mucus. Therefore it would be possible to use
      bromelain to increase the permeability of nanoparticles through mucus without
      destroying the gel and leaving the underlying mucosa unprotected. 

PMID- 25758123
TI  - Characterisation of selected active agents regarding pKa values, solubility
      concentrations and pH profiles by SiriusT3.
AB  - The aim of this work was to determine pKa values and solubility properties of
      34active agents using the SiriusT3 apparatus. The selected drug substances belong
      to the groups of ACE-inhibitors, beta-blockers, antidiabetics and lipid lowering
      substances. Experimentally obtained pKa and intrinsic solubility values were
      compared to calculated values (program ACD/ChemSketch) and pKa values to
      published data as well. Solubility-pH profiles were generated to visualise the
      substance solubility over the gastrointestinal pH range. The relationship between
      the solubility characteristic of a substance, its bioavailability and
      categorisation according to the Biopharmaceutics Classification System (BCS) was
      examined as well. The results showed a good agreement between experimentally
      obtained, calculated and published pKa values. The measured and calculated
      intrinsic solubility values indicated several major deviations. All solubility-pH
      profiles showed the expected shape and appearance for acids, bases or
      zwitterionic substances. The obtained results for the pKa and solubility
      measurements of the examined active agents may help to predict their
      physicochemical behaviour in vivo, and to understand the bioavailability of the
      substances according to their BCS categorisation. The easy and reproducible
      determination of pKa and solubility values makes the SiriusT3 apparatus a useful
      tool in early stages of drug and formulation development. 

PMID- 25758124
TI  - Nanoparticles for the treatment of ocular neovascularizations.
AB  - Neovascular diseases of the posterior eye like age-related macular degeneration,
      proliferative diabetic retinopathy or retinopathy of prematurity carry a
      tremendous burden for patient and health care system alike. Although intravitreal
      injections of anti-VEGF based therapeutics have significantly improved the visual
      outcome for many patients, current therapeutic options still show significant
      drawbacks such as the injection-related risk of contracting an infection. Due to
      their ability to encapsulate drugs with otherwise poor bioavailability,
      accumulate in areas of increased vascular permeability and control the release of
      active ingredients over time, nanoparticle systems have been widely researched to
      enhance current therapeutic strategies and expand the therapeutic arsenal. In
      this review, emphasis is placed both on the possibilities and drawbacks that a
      systemic nanoparticle-based therapy could have in the context of neovascular
      posterior eye diseases. Recent investigations into intravenous and intravitreal
      administration of nanomaterials and their potential to deliver potent drugs and
      genes to pathologic lesions will also be presented. Furthermore, we will focus on
      the exceptional anti-oxidative and anti-angiogenic properties of selected
      nanoscale systems that carve out new paths for the treatment of these severe
      posterior eye diseases. 

PMID- 25758125
TI  - Dr Walburg Maric-Oehler.

PMID- 25758126
TI  - Older Patients' Recall of Lifestyle Discussions in Primary Care.
AB  - Despite the known benefits of engaging in healthy diet and physical activity
      across the life span, suboptimal diet and physical inactivity are pervasive among
      older adults. While health care providers can promote patients' engagement in
      health behaviors, patient recall of recommendations tends to be imperfect. This
      study sought to better understand older adults' recall of dietary and physical
      activity discussions in primary care. One hundred and fifteen adults aged 65 and
      older were interviewed immediately following a routine primary care visit on
      whether and what they recalled discussing pertaining to diet and physical
      activity. Compared against transcripts, most patients accurately recalled their
      diet and physical activity discussions. The inclusion of a recommendation, and
      for diet discussions longer duration, increased the likelihood of patient recall
      for these health behavior discussions. These findings suggest that specific
      recommendations and an extra minute of discussion, at least for dietary
      discussions, increase the likelihood of accurate patient recall.

PMID- 25758127
TI  - Decreased expression and prognostic role of EHD2 in human breast carcinoma:
      correlation with E-cadherin.
AB  - Decreased expression of epithelial cadherin (E-cadherin) has been noted to
      associate with aggressiveness and metastasis of breast cancer. The aim of this
      study was to examine the effect of C-Terminal EH domain-containing protein 2
      (EHD2) expression on E-cadherin and related mechanism in the metastasis of breast
      cancer. Immunohistochemical analysis was performed in 96 human breast carcinoma
      samples and the data were correlated with clinicopathologic characteristics.
      Furthermore, Western blot analysis was performed for EHD2 and E-cadherin in
      breast carcinoma samples and cell lines to evaluate their protein levels and
      molecular interaction. We found that the expression of EHD2 was positively
      related with E-cadherin expression (P < 0.01), moreover, EHD2 expression was
      significantly correlated with histologic grade (P < 0.01). Meanwhile, E-cadherin
      expression obtained similar results. Kaplan-Meier survival analysis showed that
      decreased expression of EHD2 and E-cadherin exhibited a significant correlation
      with poor prognosis in human breast cancer (P < 0.01). While in vitro, we
      employed siRNA technique to knock down EHD2 expressions and observed their
      effects on breast cancer cells growth. EHD2 depletion by siRNA promoted PCNA
      expression, and it was concurrent with the decreased expression of epithelial
      marker E-cadherin and the increased expression of N-cadherin by Western blot
      analysis. Consistent with these observations, the suppression of EHD2 in breast
      cancer cells remarkably promoted cellular proliferation and migration. On the
      basis of these results, we suggested that EHD2 can inhibit the metastasis of
      human breast cancer by regulating the EMT key markers E-cadherin and N-cadherin.

PMID- 25758128
TI  - The burden of care and quality of life of caregivers of leukemia and lymphoma
      patients following peripheric stem cell transplantation.
AB  - This study was conducted to identify the burden of care and quality of life of
      caregivers of leukemia and lymphoma patients who had undergone peripheric stem
      cell transplantation. The sample consisted of 123 patient caregivers, all of whom
      were relatives. Data were collected using a survey, the Burden Interview, and the
      Caregiver Quality of Life Index Cancer Scale. Data evaluation was done using
      correlation analysis, Kruskall Wallis, and Mann-Whitney U tests. Factors that
      were significantly associated with quality of life and care burden perception
      included caring for an older patient, patient dependence for daily activities,
      and having low economic status. 

PMID- 25758129
TI  - Prevalence and factors associated with late HIV diagnosis.
AB  - While highly active antiretroviral therapy has been successful in delaying
      progression into AIDS, late HIV diagnosis remains a major contributor to the
      mortality and morbidity of AIDS. An epidemiological study was conducted to
      evaluate the prevalence and factors of late diagnosis and the characteristics of
      those individuals with late diagnosis in Liuzhou city. Patients with late
      diagnosis were defined as either those who were diagnosed with AIDS at the time
      of HIV diagnosis or as those who developed AIDS no more than 1 year after HIV
      diagnosis. Of 899 participants, 72.6% had a late diagnosis. Common
      characteristics of those who experienced late diagnosis included older
      participants, those who were unexpectedly diagnosed while seeking other medical
      attention, participants who believed they could not acquire HIV from their
      regular heterosexual partners, those who never considered getting tested for HIV,
      and patients with unexplained weight loss, angular cheilitis, or prolonged fever
      prior to HIV diagnosis. On the other hand, those participants who were diagnosed
      via testing at compulsory rehabilitation centers and those whose annual household
      income was greater than 30,000 Yuan were less likely to be diagnosed late. These
      results suggested that late HIV diagnosis is common in Liuzhou city, and it is
      essential to promote appropriate strategies to detect HIV infections earlier.
      Strategies that require HIV/AIDS patients to notify their spouse/sexual-partners
      about their HIV-positive results within one month and start provider-initiated
      HIV testing and counseling in medical facilities are beneficial to earlier HIV
      diagnosis.

PMID- 25758130
TI  - Survey find racial and ethnic diversity remains low in US pediatric departments.

PMID- 25758131
TI  - Effortful control and resiliency exhibit different patterns of cardiac autonomic
      control.
AB  - Effortful control (EC) and ego-resiliency (often shortened to resiliency) may
      similarly encode adaptability to stress. Differentiation of these traits in terms
      of autonomic control may highlight each construct's relative mechanisms in stress
      regulation. In the current study, 84 subjects self-reported levels of EC and
      resiliency and then were exposed to 3 mental stressors (mental arithmetic, speech
      preparation, verbal fluency), during which heart rate variability (HRV) was
      assessed to index cardiac vagal influences. Interbeat intervals (IBIs) were also
      collected, while pre-ejection period (PEP) and left ventricular ejection time
      (LVET) were assessed as sympathetic indices. Multiple regression was used to
      explore the extent to which autonomic control was moderated by each EC and
      resiliency. Results indicate that EC was related to concordance between IBI and
      HRV, along with negative emotion. Resiliency was more associated with coherence
      between IBI and PEP, and with positive emotion. Findings suggest that regulatory
      processes play a role in EC's adaptability to stress, while resiliency may
      involve approach motivation in stress control. 

PMID- 25758132
TI  - Francis Dov Por (1927-2014): A life dedicated to zoology remembered.

PMID- 25758135
TI  - Attachment and Family Processes in Children's Psychological Adjustment in Middle
      Childhood.
AB  - This study examined the links between parent-child attachment, whole family
      interaction patterns, and child emotional adjustment and adaptability in a sample
      of 86 community families with children between the ages of 8 and 11 years. Family
      interactions were observed and coded with the System for Coding Interactions and
      Family Functioning (SCIFF; Lindahl, 2001). Both parents and each target child
      completed the appropriate form of the Behavior Assessment System for Children-2nd
      Edition (BASC-2; Reynolds & Kamphaus, 2004). Target children also completed the
      Children's Coping Strategies Questionnaire (CCSQ; Yunger, Corby, & Perry, 2005).
      Hierarchical multiple regressions indicated that Secure mother-child attachment
      was a robust predictor of children's emotional symptoms, but father-child
      attachment strategies were not significant independent predictors. Positive
      Affect in family interactions significantly increased the amount of variance
      accounted for in children's emotional symptoms. In addition, Family Cohesion and
      Positive Affect moderated the relationship between father-child attachment and
      children's emotional symptoms. When data from all BASC-2 informants (mother,
      father, child) were considered simultaneously and multidimensional constructs
      were modeled, mother-child security directly predicted children's adjustment and
      adaptive skills, but the influence of father-child security was fully mediated
      through positive family functioning. Results of the current study support the
      utility of considering dyadic attachment and family interaction patterns
      conjointly when conceptualizing and fostering positive emotional and behavioral
      outcomes in children.

PMID- 25758134
TI  - Tolerance and efficacy of off-label anti-interleukin-1 treatments in France: a
      nationwide survey.
AB  - BACKGROUND: Despite their limited licensed indications, anti-interleukin-1 (anti
      IL-1) agents are often used in clinical practice for an increasing number of auto
      inflammatory diseases. We conducted a national cross-sectional observational
      study from January 2011 to January 2013 to record the off-label use of such
      agents in France. We aimed to estimate the off-label use of anti-IL-1 treatments
      in France, assess their efficacy in rare diseases, and increase the reporting of
      their possible side effects. METHODS: Physicians answered a questionnaire that
      covered patient and disease data, anti-IL-1 agent use, efficacy and adverse
      events. The study involved adult or paediatric patient who had received an anti
      IL-1 agent after January 2005 in France. RESULTS: In total, 189 patients from 38
      centres were included. The main diseases were adult-onset Still's disease (AOSD)
      (35), gout (28), systemic juvenile idiopathic arthritis (27), cryopyrin
      associated periodic syndrome (CAPS) (21), familial Mediterranean fever (14) and
      mevalonate kinase deficiency (12). The main off-label used agent was anakinra,
      used at least once for 185 patients, with canakinumab used for 25. Anakinra was
      effective in most patients (90%), with higher complete clinical response rates
      for Schnitzler's syndrome, gout, CAPS and AOSD. Overall, 58% of patients showed
      at least one adverse event, mainly minor injection-site reactions. The main
      reported serious adverse event was severe infection. Injection-site reactions and
      liver toxicity were significantly more frequent in children than adults. The main
      non-cutaneous adverse event was liver toxicity, significantly associated with
      treatment duration. Weight gain was reported in about 10% of patients and was
      associated with treatment duration and CAPS. Canakinumab was rarely used and
      showed better cutaneous tolerance than anakinra but similar rates of non
      cutaneous and severe adverse events. CONCLUSIONS: Anakinra was well tolerated and
      effective in most patients with various inflammatory diseases. The main adverse
      events were mild injection-site reactions, especially in children. The survey
      allowed for collecting limited information on the off-label use of canakinumab.

PMID- 25758136
TI  - Solvent dependent reactivities of di-, tetra- and hexanuclear manganese
      complexes: syntheses, structures and magnetic properties.
AB  - An unusual solvent effect on the synthesis of five manganese complexes
      [Mn2(L1)2(Py)4](), [Mn2(L1)2(DMSO)4](), [Mn4(L2)4(OH)4](),
      [Mn4(L3)2(DMSO)7(H2O)](), and [Mn6O2(L4)4(OAc)2(OMe)2(DMSO)4].MeOH] (), (H3L1 = 5
      (2-oxyphenyl)-pyrazole-3-carboxylic acid; H2L2 = 5-(2-oxyphenyl)-pyrazole-3
      carboxylic acid amide; H4L3 = di-[5-(2-oxyphenyl)-pyrazole]-3-hydroxamic ether;
      and H2L4 = 5-(2-oxyphenyl)-pyrazole-3-carboxylic acid methyl ester) has been
      reported. Five complexes have been characterized by X-ray single crystal
      diffraction, IR, element analysis, thermogravimetric analysis and UV-vis spectra.
      The analysis reveals that complexes and are isostructural with a bimetallic six
      membered ring and L1 from the decomposition of the original H4ppha (H4ppha = 5-(2
      hydroxyphenyl)-pyrazole-3-hydroxamic acid) ligand. Complexes and are two
      tetranuclear clusters, and possesses an aza12-metallacrown-4 core with L2 from
      the amide functionalization of the decomposition L1; while represents a novel
      linear [Mn4N8O2] core with L3 from the condensation of L1 and H4ppha. Complex is
      the first Mn6 cluster linked by two stacked, off-set 8-azametallacrown-3 subunits
      with [M-N-N-M-N-N-M-O] connectivity, and L4 derived from the esterification of
      L1. The magnetic behaviour of complexes show the dominant antiferromagnetic
      interactions between metal centers, whereas complex further reveals the
      coexistence of antiferromagnetic and ferromagnetic interactions, and slow
      magnetic relaxation at T < 6 K with S = 4 ground state, as well as field induced
      magnetization saturation. 

PMID- 25758141
TI  - Citricoccus zhacaiensis B-4 (MTCC 12119) a novel osmotolerant plant growth
      promoting actinobacterium enhances onion (Allium cepa L.) seed germination under
      osmotic stress conditions.
AB  - The water potential of rhizospheric soil is a key parameter that determines the
      availability of water, oxygen, and nutrients to plants and microbes. Recent
      global warming trends and erratic precipitation patterns have resulted in the
      emergence of drought as a major constraint of agricultural productivity. Though
      several strategies are being evaluated to address this issue, a novel approach is
      the utilization of microbes for alleviation of drought stress effects in crops.
      Citricoccus zhacaiensis B-4 is an osmotolerant actinobacterium isolated from
      banana rhizosphere on mannitol supplemented medium (-2.92 MPa osmotic potential).
      This isolate expressed plant growth promotion traits viz, IAA, GA3 production,
      phosphate, zinc solubilization, ACC deaminase activity and ammonia production
      under PEG induced osmotic stress and non-stress conditions. Under in vitro
      osmotic conditions, biopriming with the actinobacterium improved the percent
      germination, seedling vigour and germination rate of onion seeds (cv. Arka
      Kalyan) at osmotic potentials up to -0.8 MPa. Considering its novelty,
      osmotolerance and plant growth promoting traits, biopriming with C. zhacaiensis
      is suggested as a viable option for the promotion of onion seed germination under
      drought stressed environments.

PMID- 25758142
TI  - Heat Shock Protein 47 Promotes Glioma Angiogenesis.
AB  - Heat shock protein 47 (HSP47) is a collagen-binding protein, which has been
      recently found to express in glioma vessels. However, the expression profile of
      HSP47 in glioma patients and the underlying mechanisms of HSP47 on glioma
      angiogenesis are not fully explored. In the current study, we found that
      expression of HSP47 in glioma vessels was correlated with the grades of gliomas.
      HSP47 knockdown by siRNAs significantly decreased cell viability in vitro and
      tumor volume in vivo; moreover, it reduced the microvessel density (MVD) by CD31
      immunohistochemistry in vivo. HSP47 knockdown significantly inhibited tube
      formation, invasion and proliferation of human umbilical vein endothelial cells
      (HUVECs). Furthermore, conditional medium derived from HSP47 knockdown cells
      significantly inhibited HUVECs tube formation and migration, while it increased
      chemosensitivity of HUVECs cells to Avastin. Silencing of HSP47 decreased VEGF
      expression in glioma cells consistently, and reduced glioma vasculature.
      Furthermore, HSP47 promoted glioma angiogenesis through HIF1alpha-VEGFR2
      signaling. The present study demonstrates that HSP47 promotes glioma angiogenesis
      and highlights the importance of HSP47 as an attractive therapeutic target of
      GBM. 

PMID- 25758143
TI  - Cross examination of clinicians at coroners' inquests following deaths in
      custody.
AB  - PURPOSE: This article draws upon the international literature to focus on the
      investigation of prisoner deaths in England and Wales, concentrating on clinician
      involvement in this process. DESIGN/METHODOLOGY/APPROACH: This is a viewpoint
      paper regarding clinician involvement in coroner investigations of prisoner
      deaths in England and Wales. FINDINGS: Compared to colleagues practising in the
      community, the authors suggest that there is a higher burden of investigation
      upon clinicians practicing in secure environments and recommend improved training
      for prison clinicians regarding expectations of the coroner's inquest and also a
      system whereby questioning in coroners' courts is directed through the coroner.
      ORIGINALITY/VALUE: This paper provides an updated perspective on the issue of
      coroner investigations following a death in prison custody, from the position of
      practising prison clinicians.

PMID- 25758144
TI  - Work ability and treatment needs among Finnish female prisoners.
AB  - PURPOSE: The purpose of this paper is to assess the work ability and employment
      history of Finnish female prisoners and their need for treatment.
      DESIGN/METHODOLOGY/APPROACH: The sample consisted of 101 female prisoners, with
      309 male prisoners for comparison. The methods included interviews, the
      Structured Clinical Interview for DSM-IV Axis I, II Disorders and medical
      examination including ICD-10 diagnoses. FINDINGS: Among women, 78 per cent were
      unemployed and only 6 percent were employed whereas among men, the proportion of
      those employed was four times greater than for women. Of women, 42 per cent were
      unable to work; of men 11 per cent. Substance abuse disorders were the most
      common reason for impaired work ability (over 70 per cent in both genders). Among
      women, other mental disorders were the second most common reason (39 per cent),
      somatic diseases caused impairment in 23 per cent. Basic socio-demographic
      factors were not associated with impaired work ability among women. Violent crime
      as the present main offence was significantly more common among prisoners with
      limited working capacity. Need for treatment was found in 94 per cent of women
      and 90 per cent of men. In both genders, the majority of treatment needs were for
      mental disorders. Finnish female prisoners have serious problems with substance
      abuse, of both alcohol and drugs, which impairs their work ability, employability
      and is the cause of their need for treatment. In addition, female prisoners have
      other mental disorders commonly complicating their situation. ORIGINALITY/VALUE:
      This paper is a part of the first comprehensive health study of Finnish female
      prisoners.

PMID- 25758145
TI  - Homelessness as viewed by incarcerated women: participatory research.
AB  - PURPOSE: The purpose of this paper is to describe the development, by
      incarcerated women who were members of a prison participatory health research
      team, of a survey tool regarding homelessness and housing, the survey findings
      and recommendations for policy. DESIGN/METHODOLOGY/APPROACH: A survey was
      developed by incarcerated women in a minimum/medium security women's prison in
      Canada. Associations were examined between socio-demographic factors and reports
      of difficulty finding housing upon release, homelessness contributing to a return
      to crime, and a desire for relocation to another city upon release. Open-ended
      questions were examined to look for recurrent themes and to illuminate the survey
      findings. FINDINGS: In total, 83 women completed the survey, a 72 per cent
      response rate. Of the 71 who were previously incarcerated, 56 per cent stated
      that homelessness contributed to their return to crime. Finding housing upon
      release was a problem for 63 per cent and 34 per cent desired relocation to
      another city upon release. Women indicated that a successful housing plan should
      incorporate flexible progressive staged housing. RESEARCH
      LIMITATIONS/IMPLICATIONS: The present study focuses only on incarcerated women
      but could be expanded in future to include men. PRACTICAL IMPLICATIONS:
      Incarcerated women used the findings to create a housing proposal for prison
      leavers and created a resource database of the limited housing resources for
      women prison leavers. SOCIAL IMPLICATIONS: Lack of suitable housing is a major
      factor leading to recidivism. This study highlights the reality of the cycle of
      homelessness, poverty, crime for survival, street-life leading to drug use and
      barriers to health, education and employment that incarcerated women face.
      ORIGINALITY/VALUE: Housing is a recognized basic determinant of health. No
      previous studies have used participatory research to address homelessness in a
      prison population.

PMID- 25758146
TI  - The role of sport in promoting prisoner health.
AB  - PURPOSE: The existing evidence base and policy context of sports-based prisoner
      health promotion is evaluated, and an original analysis of current provision and
      best practice in delivering sport to address physical, mental and substance
      misuse needs among prisoners across the secure estate in England and Wales is
      presented, with a focus on the variability of provision across different prison
      establishments. DESIGN/METHODOLOGY/APPROACH: Inspectorate reports published by
      Her Majesty's Inspectorate of Prisons (n=184) were analysed to assess the extent
      to which health promotion objectives are being implemented through physical
      education in prisons across England and Wales. Examples of innovative sport-based
      health promoting programmes are drawn upon in order to illustrate principles of
      best practice. FINDINGS: Despite health promotion being engrained in existing
      policy, the degree to which physical, mental health and substance misuse needs
      are addressed through sport in prison remains highly variable and locally
      contingent across the secure estate, although examples of innovative practice are
      evident. RESEARCH LIMITATIONS/IMPLICATIONS: For sport to promote prisoner health
      most effectively, tailored sports provision should be embedded within multi-modal
      interventions which draw on internal and external partnerships and promote
      opportunities for ongoing sporting participation. Further research is required to
      delineate principles of best practice applicable to discrete prisoner
      populations. ORIGINALITY/VALUE: Sport can play a key role in addressing a
      multitude of prisoner health needs whilst contributing to achieving "healthy
      prison" objectives in practice. Sport and physical activity clearly offers a
      valuable way of motivating prisoners to engage in health promoting initiatives.

PMID- 25758147
TI  - Psychiatric care in the German prison system.
AB  - PURPOSE: The purpose of this paper is to describe the nature of medical care
      within the German penal system. German prison services provide health care for
      all inmates, including psychiatric care. The reached level of equivalence of care
      and ethical problems and resource limitations are discussed and the way of
      legislation in this field since 2006 reform on federal law is described.
      DESIGN/METHODOLOGY/APPROACH: The article summarizes basic data on German prison
      health care for mentally ill inmates. The legislation process and factors of
      influence are pointed out. A description of how psychiatric care is organized in
      German prisons follows. It focuses on the actual legal situation including
      European standards of prison health care and prevention of torture, psychiatric
      care in German prisons themselves, self harm and addiction. Associated problems
      such as blood born diseases and tuberculosis are included. The interactions
      between prison staff and health care personal and ethic aspects are discussed.
      FINDINGS: The legislation process is still going on and there is still a chance
      to improve psychiatric care. Mental health problems are the major challenge for
      prison health care. Factors such as special problems of migrants, shortage of
      professionals and pure statistic data are considered. ORIGINALITY/VALUE: The
      paper provides a general overview on psychiatric services in prison and names
      weak points and strengths of the system.

PMID- 25758148
TI  - Independent review of clinical health services for prisoners.
AB  - PURPOSE: The purpose of this paper is to describe the parameters for the
      development of performance measurement of the quality of medical care behind
      bars, drawing from widely-published free-world clinical guidelines and aspects of
      care that are unique to the criminal justice arena. DESIGN/METHODOLOGY/APPROACH:
      One way to help assure that prisoners receive timely and appropriate health care
      is through independent review of health care services, to identify strengths of
      programs and opportunities for improvement. This is a quality of medical care
      assessment. When done in a systematic way, this has the potential to reduce risk
      of harm and enhance the personal health of the prisoner and improve the public
      health. Independent external review provides the best opportunity to identify and
      remedy opportunities for improvement. "External" can mean wholly independent or
      "corporate," that is, review by agency staff that has no vested interest in the
      findings at the individual facility. Recently, the methodology for assessment of
      the quality of medical care in the community has blossomed, yet there is little
      guidance on how to adapt this methodology to the prison setting. FINDINGS: This
      paper introduces a prison-oriented method for assessing clinical performance. To
      the extent possible, the author cites references to the scientific basis for the
      recommendations. Where there is no science, the author relies as much as possible
      on consensus, and in a few cases resorts to "wisdom and experience," as
      unreliable as this might be. This is a conceptual paper with a viewpoint.
      ORIGINALITY/VALUE: The paper provides guidance on reducing risk of harm and
      promoting improved health and health care for prisoners.

PMID- 25758149
TI  - Psychosocial determinants of risky sexual behaviour amongst South African male
      prison inmates in KwaZulu-Natal and Mpumalanga Provinces.
AB  - PURPOSE: To inform future intervention programmes, the purpose of this paper is
      to explore the psychosocial and contextual determinants of intention to reduce
      risky sexual behaviour amongst inmates in South African prisons.
      DESIGN/METHODOLOGY/APPROACH: A cross sectional study using interviewer
      administered questionnaires was conducted with 357 inmates across four prison
      facilities in South Africa that were involved in a pre-release health education
      intervention for parolees in two provinces. FINDINGS: About 65 per cent of
      participants were first time offenders. Almost 50 per cent were unemployed prior
      to arrest and 66 per cent were married at time of incarceration. Self-efficacy,
      general life skills efficacy and sexual communication were the strongest
      predictors of intention to reduce risky behaviour upon release. High intenders
      were significantly different from low intenders in their self-efficacy, sexual
      communication, attitudes towards condom use and the perceived norm of sex being a
      non-utilitarian transaction. RESEARCH LIMITATIONS/IMPLICATIONS: One of the key
      limitations is the low literacy levels amongst prison inmates. Data also relied
      heavily on self reports of behaviours that may have occurred prior to the
      participants being incarcerated. ORIGINALITY/VALUE: It is concluded that the
      exploration of subpopulation specific behavioural determinants is a critical step
      in the development of effective, contextually-relevant, health education
      interventions.

PMID- 25758150
TI  - Embracing external scrutiny to build bridges and genuine partnerships between
      education and clinical practice.
AB  - Despite having made significant changes and improvements since 2007, publication
      of The Mid-Staffordshire National Health Service Foundation Trust Public Inquiry
      (2013) refocused attention on the poor care standards that had taken place.
      Recommendations include far reaching national transformational changes not only
      for the National Health Service but also for professional regulatory bodies and
      other agencies linked to health and social care. This paper describes how
      external scrutiny was embraced to move staff from initial loss of confidence,
      feelings of anger and defensiveness to embracing opportunities to increase
      transparency, build bridges and genuine partnerships between universities and
      healthcare providers. Following an Extraordinary Review by the Nursing and
      Midwifery Council an action plan was collaboratively formulated between
      Staffordshire University and Mid-Staffordshire National Health Service Foundation
      Trust. This resulted in the implementation of a Practice Learning Improvement
      Project which monitored the action plan, ensured sharing of all learning and
      production of evidence for external scrutiny. Key lessons learnt included the
      need to: move beyond mere compliance with regulatory performance indicators;
      engage senior staff in all aspects of student learning; develop candid sharing of
      soft and hard intelligence, clearly delineate placement support roles and ensure
      engagement of academics in practice has transparent outcomes for the student,
      practice and education. 

PMID- 25758151
TI  - From educational theory to clinical practice: self-regulated learning.

PMID- 25758152
TI  - Time to dial down the vaporizer?

PMID- 25758153
TI  - Some imminent but overlooked preanalytical and analytical challenges currently
      facing biomarkers and companion diagnostics.
AB  - An incredibly high failure rate in the pharmaceutical industry has positioned
      personalized medicine with its prerequisite drug-diagnostic codevelopment,
      commonly known as companion diagnostics (CDx), in the frontline as an potential
      rescuer. This hopefulness is potentiated by the recent major advances and
      competitiveness in molecular diagnostics, making laboratory tests widely
      accessible at affordable prices. If executed correctly, biomarkers and CDx can
      potentially help the drug industry by enhancing the probability of success and
      possibly accelerating time to market; help the diagnostics industry develop tests
      utilizing precious, clinically annotated human samples; and, more importantly,
      benefit patients by supporting accurate diagnosis and selection of the most
      efficacious and least toxic therapies. However, this spectacular road is not yet
      paved, and it faces an enormous number of challenges. This paper will list these
      challenges and highlight some critical problems with representative examples of
      imminent but still overlooked preanalytical and analytical variables that can
      defeat the whole purpose of biomarkers and CDx and mislead drug developers and
      clinicians. The paper will provide some suggestions for mitigation. 

PMID- 25758155
TI  - Combined neurocognitive and metacognitive rehabilitation in schizophrenia:
      Effects on bias against disconfirmatory evidence.
AB  - BACKGROUND: A Metacognitive Training for Schizophrenia patients (MCT) was
      developed to target the cognitive biases that characterize the illness. Results
      suggest positive MCT effects encompassing several aspects of psychopathology and
      subjective well-being. There are still open questions concerning the effect on
      different cognitive biases and the interplay between them and both
      psychopathology and neurocognition. Specifically, the bias against
      disconfirmatory evidence (BADE) has never been tested in previous trials on MCT.
      In this study we evaluated the feasibility of MCT combined with a cognitive
      remediation therapy (CACR) in schizophrenia and its effect on BADE. Moreover, we
      investigated the relationships between BADE and both neuropsychology and
      psychopathology, taking into account mutual influences on the degree of
      improvement. METHODS: Fifty-seven schizophrenia outpatients were randomly
      assigned to CACR + control group or MCT+CACR and assessed at baseline and after
      treatment for psychopathology, neurocognition and BADE. RESULTS: After MCT+CACR
      patients showed significantly greater improvements on BADE. Although BADE
      baseline performances correlated with several cognitive domains, no association
      was found between BADE improvement and neurocognitive nor psychopathological
      measures. CONCLUSIONS: This study enlightened for the first time the efficacy of
      MCT+CACR on BADE in schizophrenia, suggesting the importance to develop a more
      specific intervention tailored on individual needs of patients.

PMID- 25758154
TI  - DNA methyltransferase DNMT3A associates with viral proteins and impacts HSV-1
      infection.
AB  - Viral infections can alter the cellular epigenetic landscape, through modulation
      of either DNA methylation profiles or chromatin remodeling enzymes and histone
      modifications. These changes can act to promote viral replication or host
      defense. Herpes simplex virus type 1 (HSV-1) is a prominent human pathogen, which
      relies on interactions with host factors for efficient replication and spread.
      Nevertheless, the knowledge regarding its modulation of epigenetic factors
      remains limited. Here, we used fluorescently-labeled viruses in conjunction with
      immunoaffinity purification and MS to study virus-virus and virus-host protein
      interactions during HSV-1 infection in primary human fibroblasts. We identified
      interactions among viral capsid and tegument proteins, detecting phosphorylation
      of the capsid protein VP26 at sites within its UL37-binding domain, and an
      acetylation within the major capsid protein VP5. Interestingly, we found a
      nuclear association between viral capsid proteins and the de novo DNA
      methyltransferase DNA (cytosine-5)-methyltransferase 3A (DNMT3A), which we
      confirmed by reciprocal isolations and microscopy. We show that drug-induced
      inhibition of DNA methyltransferase activity, as well as siRNA- and shRNA
      mediated DNMT3A knockdowns trigger reductions in virus titers. Altogether, our
      results highlight a functional association of viral proteins with the mammalian
      DNA methyltransferase machinery, pointing to DNMT3A as a host factor required for
      effective HSV-1 infection. 

PMID- 25758156
TI  - The Brief Negative Symptom Scale (BNSS): Independent validation in a large sample
      of Italian patients with schizophrenia.
AB  - BACKGROUND: The Brief Negative Symptom Scale (BNSS) was developed to address the
      main limitations of the existing scales for the assessment of negative symptoms
      of schizophrenia. The initial validation of the scale by the group involved in
      its development demonstrated good convergent and discriminant validity, and a
      factor structure confirming the two domains of negative symptoms (reduced
      emotional/verbal expression and anhedonia/asociality/avolition). However, only
      relatively small samples of patients with schizophrenia were investigated.
      Further independent validation in large clinical samples might be instrumental to
      the broad diffusion of the scale in clinical research. METHODS: The present study
      aimed to examine the BNSS inter-rater reliability, convergent/discriminant
      validity and factor structure in a large Italian sample of outpatients with
      schizophrenia. RESULTS: Our results confirmed the excellent inter-rater
      reliability of the BNSS (the intraclass correlation coefficient ranged from 0.81
      to 0.98 for individual items and was 0.98 for the total score). The convergent
      validity measures had r values from 0.62 to 0.77, while the divergent validity
      measures had r values from 0.20 to 0.28 in the main sample (n=912) and in a
      subsample without clinically significant levels of depression and extrapyramidal
      symptoms (n=496). The BNSS factor structure was supported in both groups.
      CONCLUSIONS: The study confirms that the BNSS is a promising measure for
      quantifying negative symptoms of schizophrenia in large multicenter clinical
      studies.

PMID- 25758157
TI  - Benzimidazoles and benzoxazoles via the nucleophilic addition of anilines to
      nitroalkanes.
AB  - PPA-induced umpolung triggers efficient nucleophilic addition of unactivated
      anilines to nitroalkanes to produce N-hydroxyimidamides. The latter undergo
      sequential acid-promoted cyclocondensation with ortho-OH or ortho-NHR moieties to
      afford benzoxazoles and benzimidazoles, respectively. 

PMID- 25758158
TI  - Inter-subject variability in intestinal drug solubility.
AB  - Variability in oral drug absorption is a well-known phenomenon, but it is often
      overlooked for its potential effects in oral drug delivery. Understanding the
      mechanisms behind absorption variability is crucial to understanding and
      predicting drug pharmacokinetics. In this study, the solubility of furosemide and
      dipyridamole - drugs known to have highly variable oral bioavailabilities - was
      investigated in individual ileostomy fluids from 10 subjects with ulcerative
      colitis. For comparison, drug solubility was also determined in pooled upper
      gastrointestinal fluids from healthy human subjects and simulated intestinal
      fluids. Ileostomy fluid characterization revealed high variability in buffer
      capacity and to a lesser degree for pH. Drug solubility in ileostomy fluids
      showed high variability. Correlation analysis revealed that dipyridamole
      solubility in these fluids is pH-dependent, whereas furosemide solubility was
      highly correlated to buffer capacity and pH. The implications of these results
      might partly explain the high variability in bioavailability in vivo, assuming
      that most of the observed variability is due to the absorption, and not the
      elimination, process.

PMID- 25758159
TI  - Porous molybdenum carbide nano-octahedrons synthesized via confined carburization
      in metal-organic frameworks for efficient hydrogen production.
AB  - Electrochemical water splitting has been considered as a promising approach to
      produce clean and sustainable hydrogen fuel. However, the lack of high
      performance and low-cost electrocatalysts for hydrogen evolution reaction hinders
      the large-scale application. As a new class of porous materials with tunable
      structure and composition, metal-organic frameworks have been considered as
      promising candidates to synthesize various functional materials. Here we
      demonstrate a metal-organic frameworks-assisted strategy for synthesizing
      nanostructured transition metal carbides based on the confined carburization in
      metal-organic frameworks matrix. Starting from a compound consisting of copper
      based metal-organic frameworks host and molybdenum-based polyoxometalates guest,
      mesoporous molybdenum carbide nano-octahedrons composed of ultrafine
      nanocrystallites are successfully prepared as a proof of concept, which exhibit
      remarkable electrocatalytic performance for hydrogen production from both acidic
      and basic solutions. The present study provides some guidelines for the design
      and synthesis of nanostructured electrocatalysts. 

PMID- 25758160
TI  - Redox-dependent spatially resolved electrochemistry at graphene and graphite step
      edges.
AB  - The electrochemical (EC) behavior of mechanically exfoliated graphene and highly
      oriented pyrolytic graphite (HOPG) is studied at high spatial resolution in
      aqueous solutions using Ru(NH3)6(3+/2+) as a redox probe whose standard potential
      sits close to the intrinsic Fermi level of graphene and graphite. When scanning
      electrochemical cell microscopy (SECCM) data are coupled with that from
      complementary techniques (AFM, micro-Raman) applied to the same sample area,
      different time-dependent EC activity between the basal planes and step edges is
      revealed. In contrast, other redox couples (ferrocene derivatives) whose
      potential is further removed from the intrinsic Fermi level of graphene and
      graphite show uniform and high activity (close to diffusion-control). Macroscopic
      voltammetric measurements in different environments reveal that the time
      dependent behavior after HOPG cleavage, peculiar to Ru(NH3)6(3+/2+), is not
      associated particularly with any surface contaminants but is reasonably
      attributed to the spontaneous delamination of the HOPG with time to create
      partially coupled graphene layers, further supported by conductive AFM
      measurements. This process has a major impact on the density of states of
      graphene and graphite edges, particularly at the intrinsic Fermi level to which
      Ru(NH3)6(3+/2+) is most sensitive. Through the use of an improved voltammetric
      mode of SECCM, we produce movies of potential-resolved and spatially resolved
      HOPG activity, revealing how enhanced activity at step edges is a subtle effect
      for Ru(NH3)6(3+/2+). These latter studies allow us to propose a microscopic model
      to interpret the EC response of graphene (basal plane and edges) and aged HOPG
      considering the nontrivial electronic band structure. 

PMID- 25758161
TI  - Update for 2014 on clinical cardiology, geriatric cardiology, and heart failure
      and transplantation.
AB  - In the present article, we review publications from the previous year in the
      following 3 areas: clinical cardiology, geriatric cardiology, and heart failure
      and transplantation. Among the new developments in clinical cardiology are
      several contributions from Spanish groups on tricuspid and aortic regurgitation,
      developments in atrial fibrillation, syncope, and the clinical characteristics of
      heart disease, as well as various studies on familial heart disease and chronic
      ischemic heart disease. In geriatric cardiology, the most relevant studies
      published in 2014 involve heart failure, degenerative aortic stenosis, and data
      on atrial fibrillation in the geriatric population. In heart failure and
      transplantation, the most noteworthy developments concern the importance of
      multidisciplinary units and patients with preserved systolic function. Other
      notable publications were those related to iron deficiency, new drugs, and new
      devices and biomarkers. Finally, we review studies on acute heart failure and
      transplantation, such as inotropic drugs and ventricular assist devices. 

PMID- 25758162
TI  - Cardiorenal Syndrome in Acute Heart Failure: Revisiting Paradigms.
AB  - Cardiorenal syndrome has been defined as the simultaneous dysfunction of both the
      heart and the kidney. Worsening renal function that occurs in patients with acute
      heart failure has been classified as cardiorenal syndrome type 1. In this
      setting, worsening renal function is a common finding and is due to complex,
      multifactorial, and not fully understood processes involving hemodynamic (renal
      arterial hypoperfusion and renal venous congestion) and nonhemodynamic factors.
      Traditionally, worsening renal function has been associated with worse outcomes,
      but recent findings have revealed mixed and heterogeneous results, perhaps
      suggesting that the same phenotype represents a diversity of pathophysiological
      and clinical situations. Interpreting the magnitude and chronology of renal
      changes together with baseline renal function, fluid overload status, and
      clinical response to therapy might help clinicians to unravel the clinical
      meaning of renal function changes that occur during an episode of heart failure
      decompensation. In this article, we critically review the contemporary evidence
      on the pathophysiology and clinical aspects of worsening renal function in acute
      heart failure. 

PMID- 25758163
TI  - Sub-amorphous thermal conductivity in ultrathin crystalline silicon nanotubes.
AB  - Thermal transport behavior in nanostructures has become increasingly important
      for understanding and designing next generation electronic and energy devices.
      This has fueled vibrant research targeting both the causes and ability to induce
      extraordinary reductions of thermal conductivity in crystalline materials, which
      has predominantly been achieved by understanding that the phonon mean free path
      (MFP) is limited by the characteristic size of crystalline nanostructures, known
      as the boundary scattering or Casimir limit. Herein, by using a highly sensitive
      measurement system, we show that crystalline Si (c-Si) nanotubes (NTs) with shell
      thickness as thin as ~5 nm exhibit a low thermal conductivity of ~1.1 W m(-1) K(
      1). Importantly, this value is lower than the apparent boundary scattering limit
      and is even about 30% lower than the measured value for amorphous Si (a-Si) NTs
      with similar geometries. This finding diverges from the prevailing general notion
      that amorphous materials represent the lower limit of thermal transport but can
      be explained by the strong elastic softening effect observed in the c-Si NTs,
      measured as a 6-fold reduction in Young's modulus compared to bulk Si and nearly
      half that of the a-Si NTs. These results illustrate the potent prospect of
      employing the elastic softening effect to engineer lower than amorphous, or
      subamorphous, thermal conductivity in ultrathin crystalline nanostructures. 

PMID- 25758164
TI  - Polyphenols from artichoke heads (Cynara cardunculus (L.) subsp. scolymus Hayek):
      in vitro bio-accessibility, intestinal uptake and bioavailability.
AB  - Artichoke is a rich source of health promoting compounds such as polyphenols,
      important for their pharmaceutical and nutritional properties. In this study, the
      potential for bioavailability of the artichoke polyphenols was estimated by using
      both in vitro digestion and Caco-2 human intestinal cell models. In vitro
      digestive recoveries (bio-accessibility) were found to be 55.8% for total
      artichoke phenolics and in particular, 70.0% for chlorogenic acid, 41.3% for 3,5
      O-dicaffeoylquinic acid, and 50.3% for 1,5-O-dicaffeoylquinic acid, highlighting
      potential sensitivity of these compounds to gastric and small intestinal
      digestive conditions. Uptake of artichoke polyphenols was rapid with peak
      accumulation occurring after 30 min with an efficiency of 0.16%, according to the
      poor uptake of dietary polyphenols. Some compounds, such as coumaric acid,
      caffeic acid and caffeic acid derivatives, were also detected in the basolateral
      side assuming extra and intracellular esterase activities on chlorogenic acid.
      Only apigenin-7-O-glucoside was transported through the Caco-2 monolayer
      demonstrating its bioavailability to the extent of 1.15% at 60 min. In addition,
      permeability coefficient (Papp = 2.29 * 10(-5) cm s(-1)), involving apical to
      basolateral transport of apigenin 7-O-glucoside, was calculated to facilitate
      estimation of transport through the Caco-2 monolayer. Finally, the mono and
      dicaffeoylquinic acids present in artichoke heads exert an antioxidant activity
      on the human low density lipoprotein system correlated to their chemical
      structure. In conclusion, the utilized in vitro models, although not fully
      responding to the morphological and physiological features of human in vivo
      conditions, could be a useful tool for investigating mechanistic effects of
      polyphenols released from the food matrix. 

PMID- 25758165
TI  - Anti-miR-21 Suppresses Hepatocellular Carcinoma Growth via Broad Transcriptional
      Network Deregulation.
AB  - Hepatocellular carcinoma (HCC) remains a significant clinical challenge with few
      therapeutic options available to cancer patients. MicroRNA 21-5p (miR-21) has
      been shown to be upregulated in HCC, but the contribution of this oncomiR to the
      maintenance of tumorigenic phenotype in liver cancer remains poorly understood.
      We have developed potent and specific single-stranded oligonucleotide inhibitors
      of miR-21 (anti-miRNAs) and used them to interrogate dependency on miR-21 in a
      panel of liver cancer cell lines. Treatment with anti-miR-21, but not with a
      mismatch control anti-miRNA, resulted in significant derepression of direct
      targets of miR-21 and led to loss of viability in the majority of HCC cell lines
      tested. Robust induction of caspase activity, apoptosis, and necrosis was noted
      in anti-miR-21-treated HCC cells. Furthermore, ablation of miR-21 activity
      resulted in inhibition of HCC cell migration and suppression of clonogenic
      growth. To better understand the consequences of miR-21 suppression, global gene
      expression profiling was performed on anti-miR-21-treated liver cancer cells,
      which revealed striking enrichment in miR-21 target genes and deregulation of
      multiple growth-promoting pathways. Finally, in vivo dependency on miR-21 was
      observed in two separate HCC tumor xenograft models. In summary, these data
      establish a clear role for miR-21 in the maintenance of tumorigenic phenotype in
      HCC in vitro and in vivo. IMPLICATIONS: miR-21 is important for the maintenance
      of the tumorigenic phenotype of HCC and represents a target for pharmacologic
      intervention.

PMID- 25758166
TI  - Molecular-based approaches to characterize coastal microbial community and their
      potential relation to the trophic state of Red Sea.
AB  - Molecular-based approaches were used to characterize the coastal microbiota and
      to elucidate the trophic state of Red Sea. Nutrient content and enterococci
      numbers were monitored, and used to correlate with the abundance of microbial
      markers. Microbial source tracking revealed the presence of >1 human-associated
      Bacteroides spp. at some of the near-shore sampling sites and at a heavily
      frequented beach. Water samples collected from the beaches had occasional
      exceedances in enterococci numbers, higher total organic carbon (TOC, 1.48-2.18
      mg/L) and nitrogen (TN, 0.15-0.27 mg/L) than that detected in the near-shore
      waters. Enterococci abundances obtained from next-generation sequencing did not
      correlate well with the cultured enterococci numbers. The abundance of certain
      genera, for example Arcobacter, Pseudomonas and unclassified Campylobacterales,
      was observed to exhibit slight correlation with TOC and TN. Low abundance of
      functional genes accounting for up to 41 copies/L of each Pseudomonas aeruginosa
      and Campylobacter coli were detected. Arcobacter butzleri was also detected in
      abundance ranging from 111 to 238 copies/L. Operational taxonomic units (OTUs)
      associated with cyanobacteria, Prochlorococcus, Ostreococcus spp. and Gramella
      were more prevalent in waters that were likely impacted by urban runoffs and
      recreational activities. These OTUs could potentially serve as quantifiable
      markers indicative of the water quality. 

PMID- 25758169
TI  - The relationship between audience mentality and attitudes towards healthy
      lifestyle promotion in the mass media.
AB  - Health promoters who use the mass media to encourage people to change their
      health behaviours usually underestimate the importance of audience's mental
      predispositions, which may determine their susceptibility to such influences.
      This paper presents research findings that show how some elements of an
      audience's mentality are related to their attitudes towards healthy lifestyle
      promotion in the mass media (HLPMM). The research project, undertaken between
      2007 and 2009, comprised: a qualitative study using in-depth interviews (N=30); a
      self-administered survey on a purposive sample (N=237) and a computer-assisted
      personal interview or interviewing (CAPI) survey on a representative sample of
      Polish adult population (N=934). The findings from the first two studies were
      used to construct a scale to investigate the attitude towards HLPMM. This scale
      was applied in a nation wide survey and, as a result, four dimensions of the
      attitude were identified: (1) appraisal of the idea of HLPMM; (2) appraisal of
      HLPMM practice; (3) propensity to receive media messages promoting healthy
      lifestyle and (4) propensity to avoid such messages. Moreover, the survey results
      confirmed the hypotheses whereby a higher degree of individualism, a higher
      degree of authoritarianism, a weaker demanding orientation and generalised trust
      are related to a more positive attitude towards HLPMM. The aforementioned
      relationships indicate that producers of media messages promoting a healthy
      lifestyle need to take account of their audience's mentality, since knowledge of
      mental predispositions of the target audience may help them make the message more
      suitable for specific recipients. 

PMID- 25758167
TI  - Abnormal White Matter Blood-Oxygen-Level-Dependent Signals in Chronic Mild
      Traumatic Brain Injury.
AB  - Concussion, or mild traumatic brain injury (mTBI), can cause persistent
      behavioral symptoms and cognitive impairment, but it is unclear if this condition
      is associated with detectable structural or functional brain changes. At two
      sites, chronic mTBI human subjects with persistent post-concussive symptoms
      (three months to five years after injury) and age- and education-matched healthy
      human control subjects underwent extensive neuropsychological and visual tracking
      eye movement tests. At one site, patients and controls also performed the visual
      tracking tasks while blood-oxygen-level-dependent (BOLD) signals were measured
      with functional magnetic resonance imaging. Although neither neuropsychological
      nor visual tracking measures distinguished patients from controls at the level of
      individual subjects, abnormal BOLD signals were reliably detected in patients.
      The most consistent changes were localized in white matter regions: anterior
      internal capsule and superior longitudinal fasciculus. In contrast, BOLD signals
      were normal in cortical regions, such as the frontal eye field and intraparietal
      sulcus, that mediate oculomotor and attention functions necessary for visual
      tracking. The abnormal BOLD signals accurately differentiated chronic mTBI
      patients from healthy controls at the single-subject level, although they did not
      correlate with symptoms or neuropsychological performance. We conclude that
      subjects with persistent post-concussive symptoms can be identified years after
      their TBI using fMRI and an eye movement task despite showing normal structural
      MRI and DTI. 

PMID- 25758170
TI  - Awareness regarding oral cancer and oral precancerous lesions among rural
      population of Belgaum district, India.
AB  - Belgaum district of Karnataka state is well known for high production and
      consumption of tobacco in Southern India. This study aimed to investigate the
      rural population's awareness of oral cancer, precancerous lesions and their risk
      factors. Data were collected via face to face interviews using a pretested and
      validated questionnaire. The questionnaire comprised two parts: part one had
      questions concerning socio-demographic data and part two consisted of 25
      questions pertaining to people's attitudes to and awareness of risk factors for
      oral cancer and precancerous lesions. One researcher interviewed participants and
      recorded the responses verbatim. Of the participants, 17% identified all the
      symptoms of oral cancer and 27.8% identified all the symptoms of oral
      precancerous lesions. Approximately 90% of the participants had never noticed
      statutory warnings on tobacco and alcohol products. Awareness was especially poor
      in people of lower socio-economic status. This study highlights a need for
      education concerning the risk factors for oral cancer, its clinical
      manifestations and the impact of adverse habits on long term health. Health
      education campaigns emphasizing oral cancer need to be integrated with broader
      public health messages. 

PMID- 25758168
TI  - Transcriptome analysis of cyst formation in Rhodospirillum centenum reveals large
      global changes in expression during cyst development.
AB  - BACKGROUND: Rhodospirillum centenum is a photosynthetic member of the Gram
      negative Azospirillum clade members of which exhibit a complex developmental life
      cycle featuring morphologically distinct cell types. Under periods of nutrient
      deprivation, replicative vegetative cells differentiate into metabolically
      dormant cysts that survive harsh environmental stresses such as desiccation.
      Encystment involves a multi-stage developmental process that includes the
      rounding of cells, production of large intracellular storage granules of poly
      hydroxybutyrate (PHB) and the excretion of a protective exopolysaccharide coating
      that envelops dormant cysts. RESULTS: To study the process of cyst development,
      we performed RNA-seq studies on cells that were induced to undergo cyst
      development. To assay for temporal changes in gene expression, RNA was extracted
      at 4, 24, 48, 72, 96 hours during development and subjected to deep sequence
      analysis. These results show that 812 genes exhibit log2 >= 1.5-fold changes in
      expression over a 96 hour cyst induction period demonstrating large global
      changes in gene expression during cyst development. CONCLUSIONS: Notable changes
      in expression occurred in numerous genes involved in cell wall and lipid
      biosynthesis, metabolic enzymes, and numerous regulatory genes such as histidine
      kinases and transcription factors. Many genes involved in protein synthesis and
      DNA replication were also significantly reduced during late stages of cyst
      development. Genes previously identified by genetic screens as being critical for
      cyst development also exhibited changes of expression during cyst induction. This
      study provides the first transcriptome profile of global changes in gene
      expression that occur during development of cysts in a Gram-negative species.

PMID- 25758171
TI  - Prevention and control of noncommunicable diseases through evidence-based public
      health: implementing the NCD 2020 action plan.
AB  - The control of noncommunicable diseases (NCDs) was addressed by the declaration
      of the 66th United Nations (UN) General Assembly followed by the World Health
      Organization's (WHO) NCD 2020 action plan. There is a clear need to better apply
      evidence in public health settings to tackle both behaviour-related factors and
      the underlying social and economic conditions. This article describes concepts of
      evidence-based public health (EBPH) and outlines a set of actions that are
      essential for successful global NCD prevention. The authors describe the
      importance of knowledge translation with the goal of increasing the effectiveness
      of public health services, relying on both quantitative and qualitative evidence.
      In particular, the role of capacity building is highlighted because it is
      fundamental to progress in controlling NCDs. Important challenges for capacity
      building include the need to bridge diverse disciplines, build the evidence base
      across countries and the lack of formal training in public health sciences. As
      brief case examples, several successful capacity-building efforts are highlighted
      to address challenges and further evidence-based decision making. The need for a
      more comprehensive public health approach, addressing social, environmental and
      cultural conditions, has led to government-wide and society-wide strategies that
      are now on the agenda due to efforts such as the WHO's NCD 2020 action plan and
      Health 2020: the European Policy for Health and Wellbeing. These efforts need
      research to generate evidence in new areas (e.g. equity and sustainability),
      training to build public health capacity and a continuous process of improvement
      and knowledge generation and translation. 

PMID- 25758172
TI  - Paranodal destruction and axo-glial dysjunction in a subtype of CIDP with
      anticontaction-1 antibodies.

PMID- 25758174
TI  - Wrinkle motifs in thin films.
AB  - On length scales from nanometres to metres, partial adhesion of thin films with
      substrates generates a fascinating variety of patterns, such as 'telephone cord'
      buckles, wrinkles, and labyrinth domains. Although these patterns are part of
      everyday experience and are important in industry, they are not completely
      understood. Here, we report simulation studies of a previously-overlooked
      phenomenon in which pairs of wrinkles form avoiding pairs, focusing on the case
      of graphene over patterned substrates. By nucleating and growing wrinkles in a
      controlled way, we characterize how their morphology is determined by stress
      fields in the sheet and friction with the substrate. Our simulations uncover the
      generic behaviour of avoiding wrinkle pairs that should be valid at all scales. 

PMID- 25758175
TI  - When will bigger be (recalled) better? The influence of category size on JOLs
      depends on test format.
AB  - Although it is well known that organized lists of words (e.g., categories) are
      recalled better than unrelated lists, little research has examined whether
      participants can predict how categorical relatedness influences recall. In two
      experiments, participants studied lists of words that included items from big
      categories (12 items), small categories (4 items), and unrelated items, and
      provided immediate JOLs. In Experiment 1, free recall was highest for items from
      large categories and lowest for unrelated items. Importantly, participants were
      sensitive to the effects of category size on recall, with JOLs to items from big
      categories actually increasing over the study list. In Experiment 2, one group of
      participants was cued to recall all exemplars from the categories in a blocked
      manner, whereas the other group was cued in a random order. As expected, the
      random group did not show the recall benefit for big categories over small
      categories observed in free recall, while the blocked group did. Critically, the
      pattern of metacognitive judgments closely matched actual cued recall
      performance. Participants' JOLs were sensitive to the interaction between
      category size and output order, demonstrating a relatively sophisticated strategy
      that incorporates the interaction of multiple extrinsic cues in predicting
      recall. 

PMID- 25758173
TI  - Excision of Expanded GAA Repeats Alleviates the Molecular Phenotype of
      Friedreich's Ataxia.
AB  - Friedreich's ataxia (FRDA) is an autosomal recessive neurological disease caused
      by expansions of guanine-adenine-adenine (GAA) repeats in intron 1 of the
      frataxin (FXN) gene. The expansion results in significantly decreased frataxin
      expression. We report that human FRDA cells can be corrected by zinc finger
      nuclease-mediated excision of the expanded GAA repeats. Editing of a single
      expanded GAA allele created heterozygous, FRDA carrier-like cells and
      significantly increased frataxin expression. This correction persisted during
      reprogramming of zinc finger nuclease-edited fibroblasts to induced pluripotent
      stem cells and subsequent differentiation into neurons. The expression of FRDA
      biomarkers was normalized in corrected patient cells and disease-associated
      phenotypes, such as decreases in aconitase activity and intracellular ATP levels,
      were reversed in zinc finger nuclease corrected neuronal cells. Genetically and
      phenotypically corrected patient cells represent not only a preferred disease
      relevant model system to study pathogenic mechanisms, but also a critical step
      towards development of cell replacement therapy. 

PMID- 25758176
TI  - Transfer of learning in choice reactions: The roles of stimulus type, response
      mode, and set-level compatibility.
AB  - The Simon effect refers to the advantage of responding to spatially compatible
      stimuli. This effect can be eliminated or even reversed to favor spatially
      incompatible stimuli after participants practice a choice-reaction task with
      spatially incompatible mappings (e.g., pressing left and right keys to stimuli on
      the right and left, respectively). This transfer of incompatible spatial
      associations has been observed under conditions in which responses were made
      manually (e.g., keypresses, moving a joystick). The present study used vocal
      responses to reveal the primary determinants of the transfer effect, dissociating
      the influences of stimulus type, response mode, and their interaction (set-level
      compatibility). The results suggest that contextual match between the practice
      and transfer tasks with respect to stimulus type and response mode determined
      transfer of incompatible associations to the Simon task, and stimulus type
      determined the efficiency of acquiring new associations. However, there was
      little evidence that set-level compatibility plays any major role in either
      acquisition or transfer of spatial associations. 

PMID- 25758177
TI  - Molecular cloning and sexually dimorphic expression patterns of nr0b1 and nr5a2
      in olive flounder, Paralichthys olivaceus.
AB  - The nr0b1 and nr5a2 genes, members of the nuclear receptor superfamily, are
      strong candidate genes involved in gonadal differentiation in several vertebrate
      species. In this study, an nr0b1 complementary DNA (cDNA) of 1446 bp, which
      encodes a predicted 298 amino acid protein, and an nr5a2 cDNA of 2425 bp, which
      encodes a deduced 523 amino acid protein, were obtained from olive flounder
      Paralichthys olivaceus. Both genes were expressed in multiple organ tissues of
      adult flounder, with a higher expression in ovary than in testis. Quantitative
      real-time RT-PCR was performed to investigate their temporal expression profiles
      in gonads during differentiation and at five development stages. Results
      indicated that nr0b1 and nr5a2 were expressed in primitive gonad and in the
      ensuing gonadal differentiation periods. In general, both genes were more highly
      expressed in ovary than in testis at all observed development stages. The
      expression level of cyp19a correlated with the nr5a2/nr0b1 ratio over the course
      of flounder gonadal differentiation; hence, nr0b1 and nr5a2 genes may be involved
      in flounder ovarian differentiation by regulating the expression of cyp19a.

PMID- 25758178
TI  - The role of Beclin 1 in SDT-induced apoptosis and autophagy in human leukemia
      cells.
AB  - PURPOSE: To prove the occurrence of autophagy after treatment by protoporphyrin
      IX (PpIX)-mediated sonodynamic therapy (SDT) of human chronic myelogenous
      leukemia K562 cells as well as its relationship with apoptosis. MATERIALS AND
      METHODS: The 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenylter-trazolium bromide
      tetrazolium (MTT) assay was adopted to examine cytotoxicity of different
      treatments. Nuclear morphology changes were observed under a fluorescence
      microscopy with 4'-6-Diamidino-2-Phenylindole (DAPI) staining. Western blotting
      was used to analyze the expression of caspase-3, Beclin 1 (BECN 1) and the
      conversion of LC3- phosphatidylethanolamine conjugate/a cytosolic form of LC3
      (LC3 II/I). Fluorescence microscope was used to identify the formation of
      autophagic vacuoles (AVO) during autophagy. RESULTS: Under optimal conditions,
      SDT was shown to induce autophagy in K562 cells, which caused the up-regulation
      of Beclin-1 and the formation of AVO. In addition, pre-treatment of cancer cells
      with Beclin 1-targeted short hairpin RNA (Beclin 1 shRNA) was shown to reduce the
      level of LC3-II accumulation and staining with punctate spots of
      monodansylcadaverine (MDC) staining. Besides, the cytotoxic effect of SDT was
      significantly increased by Beclin 1 shRNA. Furthermore, studies showed a marked
      effect on the apoptosis of cells by Beclin 1 shRNA to sonodamage with increased
      DAPI staining and caspase-3 cleavage. CONCLUSIONS: These results demonstrated
      that SDT significantly induced autophagy of K562 cells, probably to protect the
      K562 cells from sonodamage.

PMID- 25758179
TI  - New opportunities of real-world data from clinical routine settings in life-cycle
      management of drugs: example of an integrative approach in multiple sclerosis.
AB  - The assessment and demonstration of a positive benefit-risk balance of a drug is
      a life-long process and includes specific data from preclinical, clinical
      development and post-launch experience. However, new integrative approaches are
      needed to enrich evidence from clinical trials and sponsor-initiated
      observational studies with information from multiple additional sources,
      including registry information and other existing observational data and, more
      recently, health-related administrative claims and medical records databases. To
      illustrate the value of this approach, this paper exemplifies such a cross
      package approach to the area of multiple sclerosis, exploring also possible
      analytic strategies when using these multiple sources of information. 

PMID- 25758181
TI  - Lead aVR in wide QRS complex tachycardia-another window marker.

PMID- 25758182
TI  - Accuracy of lung ultrasound for the diagnosis of consolidations when compared to
      chest computed tomography.
AB  - OBJECTIVES: Despite emerging evidences on the clinical usefulness of lung
      ultrasound (LUS), international guidelines still do not recommend the use of
      sonography for the diagnosis of pneumonia. Our study assesses the accuracy of LUS
      for the diagnosis of lung consolidations when compared to chest computed
      tomography (CT). METHODS: This was a prospective study on an emergency department
      population complaining of respiratory symptoms of unexplained origin. All
      patients who had a chest CT scan performed for clinical reasons were
      consecutively recruited. LUS was targeted to evaluate lung consolidations with
      the morphologic characteristics of pneumonia, and then compared to CT. RESULTS:
      We analyzed 285 patients. CT was positive for at least one consolidation in 87
      patients. LUS was feasible in all patients and in 81 showed at least one
      consolidation, with a good inter-observer agreement (k = 0.83), sensitivity 82.8%
      (95% CI 73.2%-90%) and specificity 95.5% (95% CI 91.5%-97.9%). Sensitivity raised
      to 91.7% (95% CI 61.5%-98.6%) and specificity to 97.4% (95% CI 86.5%-99.6%) in
      patients complaining of pleuritic chest pain. In a subgroup of 190 patients who
      underwent also chest radiography (CXR), the sensitivity of LUS (81.4%, 95% CI
      70.7%-89.7%) was significantly superior to CXR (64.3%, 95% CI 51.9%-75.4%)
      (P<.05), whereas specificity remained similar (94.2%, 95% CI 88.4%-97.6% vs. 90%,
      95% CI 83.2%-94.7%). CONCLUSIONS: LUS represents a reliable diagnostic tool,
      alternative to CXR, for the bedside diagnosis of lung consolidations in patients
      with respiratory complains.

PMID- 25758183
TI  - Severe hydrogen sulfide intoxication treated with therapeutic hypothermia.

PMID- 25758184
TI  - Usefulness of inferior vena cava in management of heart failure.

PMID- 25758180
TI  - Circulating antigen tests and urine reagent strips for diagnosis of active
      schistosomiasis in endemic areas.
AB  - BACKGROUND: Point-of-care (POC) tests for diagnosing schistosomiasis include
      tests based on circulating antigen detection and urine reagent strip tests. If
      they had sufficient diagnostic accuracy they could replace conventional
      microscopy as they provide a quicker answer and are easier to use. OBJECTIVES: To
      summarise the diagnostic accuracy of: a) urine reagent strip tests in detecting
      active Schistosoma haematobium infection, with microscopy as the reference
      standard; and b) circulating antigen tests for detecting active Schistosoma
      infection in geographical regions endemic for Schistosoma mansoni or S.
      haematobium or both, with microscopy as the reference standard. SEARCH METHODS:
      We searched the electronic databases MEDLINE, EMBASE, BIOSIS, MEDION, and Health
      Technology Assessment (HTA) without language restriction up to 30 June 2014.
      SELECTION CRITERIA: We included studies that used microscopy as the reference
      standard: for S. haematobium, microscopy of urine prepared by filtration,
      centrifugation, or sedimentation methods; and for S. mansoni, microscopy of stool
      by Kato-Katz thick smear. We included studies on participants residing in endemic
      areas only. DATA COLLECTION AND ANALYSIS: Two review authors independently
      extracted data, assessed quality of the data using QUADAS-2, and performed meta
      analysis where appropriate. Using the variability of test thresholds, we used the
      hierarchical summary receiver operating characteristic (HSROC) model for all
      eligible tests (except the circulating cathodic antigen (CCA) POC for S. mansoni,
      where the bivariate random-effects model was more appropriate). We investigated
      heterogeneity, and carried out indirect comparisons where data were sufficient.
      Results for sensitivity and specificity are presented as percentages with 95%
      confidence intervals (CI). MAIN RESULTS: We included 90 studies; 88 from field
      settings in Africa. The median S. haematobium infection prevalence was 41% (range
      1% to 89%) and 36% for S. mansoni (range 8% to 95%). Study design and conduct
      were poorly reported against current standards. Tests for S. haematobium Urine
      reagent test strips versus microscopyCompared to microscopy, the detection of
      microhaematuria on test strips had the highest sensitivity and specificity
      (sensitivity 75%, 95% CI 71% to 79%; specificity 87%, 95% CI 84% to 90%; 74
      studies, 102,447 participants). For proteinuria, sensitivity was 61% and
      specificity was 82% (82,113 participants); and for leukocyturia, sensitivity was
      58% and specificity 61% (1532 participants). However, the difference in overall
      test accuracy between the urine reagent strips for microhaematuria and
      proteinuria was not found to be different when we compared separate populations
      (P = 0.25), or when direct comparisons within the same individuals were performed
      (paired studies; P = 0.21).When tests were evaluated against the higher quality
      reference standard (when multiple samples were analysed), sensitivity was
      marginally lower for microhaematuria (71% vs 75%) and for proteinuria (49% vs
      61%). The specificity of these tests was comparable. Antigen assayCompared to
      microscopy, the CCA test showed considerable heterogeneity; meta-analytic
      sensitivity estimate was 39%, 95% CI 6% to 73%; specificity 78%, 95% CI 55% to
      100% (four studies, 901 participants). Tests for S. mansoni Compared to
      microscopy, the CCA test meta-analytic estimates for detecting S. mansoni at a
      single threshold of trace positive were: sensitivity 89% (95% CI 86% to 92%); and
      specificity 55% (95% CI 46% to 65%; 15 studies, 6091 participants) Against a
      higher quality reference standard, the sensitivity results were comparable (89%
      vs 88%) but specificity was higher (66% vs 55%). For the CAA test, sensitivity
      ranged from 47% to 94%, and specificity from 8% to 100% (4 studies, 1583
      participants). AUTHORS' CONCLUSIONS: Among the evaluated tests for S. haematobium
      infection, microhaematuria correctly detected the largest proportions of
      infections and non-infections identified by microscopy.The CCA POC test for S.
      mansoni detects a very large proportion of infections identified by microscopy,
      but it misclassifies a large proportion of microscopy negatives as positives in
      endemic areas with a moderate to high prevalence of infection, possibly because
      the test is potentially more sensitive than microscopy.

PMID- 25758185
TI  - Incidence of advanced intravenous access in 2 urban EDs.
AB  - BACKGROUND: In an emergency department (ED), intravenous (IV) access is
      frequently accomplished by inspection and palpation of peripheral veins. Failure
      of these methods indicates severe IV access difficulty and necessitates advanced
      techniques. Here, we estimate the incidence of advanced IV access in 2 urban EDs
      with varying resident coverage. METHODS: In this multiple-cohort study, we
      enrolled data from 2 neighboring urban EDs-a tertiary care ED and a community
      hospital affiliate. The 2 have similar volumes but the tertiary care ED has more
      resident coverage (112 vs 20 hours/d). In a prospective data collection (April
      2012-2013), we enrolled consecutive patients during hours of scheduled shifts for
      research assistants. In a retrospective data collection (March 2011-2012), we
      reviewed charts of a random sample of patients from each ED for similar outcomes.
      We calculated the incidence of advanced IV access by dividing the number
      requiring advanced techniques by the number requiring IV access. RESULTS: We
      determined IV outcomes for 790 patients in the prospective cohort and 669
      patients in the retrospective cohort. Between groups, there was no difference in
      the incidence of advanced IV access in the prospective collection (P = .08) or in
      the retrospective collection (P = .7). Pooling data from both cohorts and both
      hospitals, the overall incidence was 3.2 [95% confidence interval, 1.9-5.2] per
      100 attempts. CONCLUSION: Advanced IV access is needed in 3.2% of IV attempts in
      2 urban EDs with varying levels of resident coverage. We found similar incidence
      in both EDs.

PMID- 25758186
TI  - Crystal structure of the MazG-related nucleoside triphosphate
      pyrophosphohydrolase from Thermotoga maritima MSB8.
AB  - The MazG family proteins, which are highly conserved in bacteria, are nucleoside
      triphosphate pyrophosphohydrolases that hydrolyze all canonical nucleoside
      triphosphates, and are also involved in removing noncanonical nucleoside
      triphosphates to prevent their incorporation into DNA or RNA. The primary
      structure of TM0360 from Thermotoga maritima MSB8 suggested that TM0360 is a MazG
      related nucleoside triphosphate pyrophosphohydrolase. The crystal structure of
      the TM0360 protein was determined by the MAD technique at 2.0 A resolution. The
      asymmetric unit contains an intact dimer molecule. The overall structure of
      TM0360 is similar to the known structures of the dimeric MazG protein and
      dUTPases. The putative NTP binding pocket in TM0360, identified by considering
      the probable NTP-interacting residues and structural features, suggested that
      TM0360 resembles the C-terminal domain of Escherichia coli MazG, although TM0360
      may be a truncated paralog of the N-terminal domain of T. maritima MazG (TM0913),
      according to its primary structure. The putative function of TM0360 is discussed,
      based on structural homology. 

PMID- 25758187
TI  - Metacognitive sensitivity of subjective reports of decisional confidence and
      visual experience.
AB  - Previous studies provided contradicting results regarding metacognitive
      sensitivity estimated from subjective reports of confidence in comparison to
      subjective reports of visual experience. We investigated whether this effect of
      content of subjective reports is influenced by the statistical method to quantify
      metacognitive sensitivity. Comparing logistic regression and meta-d in a masked
      orientation task, a masked shape task, and a random-dot motion task, we observed
      metacognitive sensitivity of reports regarding decisional confidence was greater
      than of reports about visual experience irrespective of mathematical procedures.
      However, the relationship between subjective reports and the logistic transform
      of accuracy was often not linear, implying that logistic regression is not a
      consistent measure of metacognitive sensitivity. We argue that a science of
      consciousness would benefit from the assessment of both visual experience and
      decisional confidence, and recommend meta-d as measure of metacognitive
      sensitivity for future studies. 

PMID- 25758188
TI  - Validation and Modification of the Japanese Classification System for Liver
      Metastases from Colorectal Cancer: A Multi-institutional Study.
AB  - BACKGROUND: A Japanese multicenter study disclosed four prognostic indicators of
      colorectal cancer liver metastases: >=5 hepatic tumors (HT), HT size > 5 cm,
      nodal status (N2) of primary cancer, and the presence of extrahepatic metastases
      (EM). The Japanese classification was then defined as Stage A, HT1 (<=4 lesions
      and <=5 cm) and N0/1; Stage B, HT2 (>=5 lesions or >5 cm) and N0/1, or HT1 and
      N2; and Stage C, HT2 and N2, HT3 (>=5 lesions and >5 cm) with any N, or EM1
      (presence of EM) with any HT/N. This study aimed to validate the prognostic
      reliability in a recent population and to develop a modified staging system that
      divided Stage C patients. METHODS: A total of 1185 patients diagnosed with liver
      metastases between 2007 and 2008 were enrolled in the study. According to the
      classification, 358, 257, and 570 patients were categorized as Stages A, B, and
      C, respectively. Stage C was further divided into two groups: Stage C-I, HT3 and
      N0/1, HT2 and N2, or HT1 and EM1; and Stage C-II, HT3 and N2, or HT2/3 and EM1.
      RESULTS: Cumulative overall survival curves for Stages A, B, and C were
      significantly different between each two stages (p < 0.0001, p < 0.0001). The
      modified system discriminated patients with a relatively better outcome (Stage C
      I) from desperate patients (Stage C-II) (p < 0.0001). CONCLUSIONS: The Japanese
      classification system was adequately validated in a recent population, and the
      modified system is useful in risk stratification of Stage C cases.

PMID- 25758189
TI  - The Influence of Aging on Hepatic Regeneration and Early Outcome after Portal
      Vein Occlusion: A Case-Control Study.
AB  - BACKGROUND: Portal vein occlusion (PVO) is used to increase inadequate future
      liver remnant volume (FLRV). Impaired liver regeneration has been reported in
      aged animals. This study was designed to evaluate the impact of patient age on
      hepatic regeneration. METHODS: Sixty patients aged >=70 years were matched 1:1
      with 60 patients aged <70 years. Matching criteria were sex, diabetes, cirrhosis,
      pre-PVO chemotherapy and bevacizumab administration, and jaundice. RESULTS: The
      median ages in the older and younger groups were 76 (range 70-83) years and 59
      (range 20-69) years, respectively (p < 0.001). Median FLRV following PVO (33.1 +/
      6.8 vs. 31.9 +/- 6.0 %) and volumetric increase (0.52 +/- 0.35 vs. 0.49 +/-
      0.34) were similar in the two groups. Of the older and younger patients, 10 % and
      1.7 %, respectively, did not undergo liver surgery after PVO (p = 0.051).
      Mortality (5.5 vs. 6.7 %) and major morbidity (25.9.8 vs. 22 %) rates were
      similar. Liver failure rate was higher in older patients (35.1 vs. 16.9 %, p <
      0.026), mainly due to Grade A liver failure (20.3 vs. 8.4 %, p < 0.001).
      Multivariate analysis showed that age >= 70 years [odds ratio (OR) 3.03; 95 %
      confidence interval (CI) 1.18-7.78; p = 0.020] and biliary cancer diagnosis (OR
      4.69; 95 % CI 1.81-12.09; p = 0.001) were independent risk factors for
      postoperative liver failure. CONCLUSIONS: Liver regeneration after PVO is not
      impaired by age. Nevertheless, liver resection in elderly patients is performed
      less often after PVO and carries a higher risk of liver failure.

PMID- 25758190
TI  - Prognostic Factors of 30-Day Mortality After Palliative Procedures in Patients
      with Malignant Pleural Effusion.
AB  - BACKGROUND: The aim of this study was to identify predictors of 30-day mortality
      in patients with malignant pleural effusion (MPE) who need pleural palliative
      procedures. METHODS: Data was prospectively collected from our database, between
      January 2013 and July 2014 on 86 patients with MPE and complete follow-up 30 days
      after the procedure. The sample was divided into two groups. The first group (G1)
      included patients who had died up to 30 days after the palliative procedure, and
      the second group (G2) included patients who survived for more than 30 days after
      the palliative procedure. The identification of prognostic factors occurred
      through univariate analysis using Fisher exact test for analysis of categorical
      variables and the t test for quantitative variables. Subsequently, all variables
      were used in the multivariate logistic regression analysis. The cutoff values for
      any significant continuous variables were determined by receiver operating
      characteristics analysis. RESULTS: There were 24 patients in G1 and 62 patients
      in G2. Univariate analysis of factors affecting postprocedural survival disclosed
      nine factors that were associated with significantly reduced postoperative
      survival. At the multivariate analysis, high levels of white blood cells, (p =
      .013), low levels of red blood cells (p < .0001) and protein in pleural fluid (p
      = .001), and primary lung and gastrointestinal sites (p = .0076) were identified
      as independent predictors of mortality. CONCLUSIONS: We identified four factors
      that are easily recognized in daily practice and can help select patients with
      low life expectancy. Therefore, invasive procedures and hospitalizations for this
      subgroup of patients can be prevented.

PMID- 25758191
TI  - Feasibility and Safety of Negative-Balance Isolated Pelvic Perfusion in Patients
      with Pretreated Recurrent or Persistent Uterine Cervical Cancer.
AB  - BACKGROUND: Second-line therapy has limited activity in patients with recurrent
      or persistent uterine cervical cancer that has progressed after chemoradiation
      and palliative chemotherapy. The purpose of this study was to evaluate the
      efficacy of negative-balance isolated pelvic perfusion (NIPP) in patients with
      pretreated recurrent/persistent uterine cervical cancer. METHODS: Between April
      2004 and May 2013, a total of 26 patients with recurrent or persistent uterine
      cervical cancer previously treated with platinum-based systemic chemotherapy
      and/or chemoradiotherapy received NIPP therapy at our institution, consisting of
      a 30-min isolated pelvic perfusion with cisplatin and fluorouracil, followed by
      isolated pelvic dialysis. Primary endpoints were response rate (RR) and
      progression-free survival (PFS), while secondary endpoints were overall survival
      (OS) and safety. Platinum pharmacokinetics were also evaluated. RESULTS: The RR
      was 57.7 % (complete response, five patients; partial response, ten patients).
      The median PFS and OS after NIPP therapy were 11.0 (95 % confidence interval [CI]
      6.6-15.4) and 25.1 (95 % CI 17.1-33.1) months, respectively. PFS was
      significantly better in patients without intestinal involvement (p = 0.016) or
      dissemination (p < 0.001). Survival rates at 1, 2, and 3 years after initial NIPP
      therapy were 65.2, 50.4, and 13.4 %, respectively. The plasma pelvic-to-systemic
      exposure ratios were 15.4 and 15.8, based on the maximum concentration and the
      concentration-time curve, respectively. Most adverse events were mild (grade 1-2)
      (Common Terminology Criteria for Adverse Events, version 3.0). Severe neutropenia
      (grade 3 or higher) occurred in only 7.7 % of patients. CONCLUSIONS: NIPP appears
      to be an effective and feasible method for patients with pretreated recurrent or
      persistent cervical cancer.

PMID- 25758192
TI  - Does Vaping in E-Cigarette Advertisements Affect Tobacco Smoking Urge,
      Intentions, and Perceptions in Daily, Intermittent, and Former Smokers?
AB  - Visual depictions of vaping in electronic cigarette advertisements may serve as
      smoking cues to smokers and former smokers, increasing urge to smoke and smoking
      behavior, and decreasing self-efficacy, attitudes, and intentions to quit or
      abstain. After assessing baseline urge to smoke, 301 daily smokers, 272
      intermittent smokers, and 311 former smokers were randomly assigned to view three
      e-cigarette commercials with vaping visuals (the cue condition) or without vaping
      visuals (the no-cue condition), or to answer unrelated media use questions (the
      no-ad condition). Participants then answered a posttest questionnaire assessing
      the outcome variables of interest. Relative to other conditions, in the cue
      condition, daily smokers reported greater urge to smoke a tobacco cigarette and a
      marginally significantly greater incidence of actually smoking a tobacco
      cigarette during the experiment. Former smokers in the cue condition reported
      lower intentions to abstain from smoking than former smokers in other conditions.
      No significant differences emerged among intermittent smokers across conditions.
      These data suggest that visual depictions of vaping in e-cigarette commercials
      increase daily smokers' urge to smoke cigarettes and may lead to more actual
      smoking behavior. For former smokers, these cues in advertising may undermine
      abstinence efforts. Intermittent smokers did not appear to be reactive to these
      cues. A lack of significant differences between participants in the no-cue and no
      ad conditions compared to the cue condition suggests that visual depictions of e
      cigarettes and vaping function as smoking cues, and cue reactivity is the
      mechanism through which these effects were obtained. 

PMID- 25758193
TI  - Graded porous inorganic materials derived from self-assembled block copolymer
      templates.
AB  - Graded porous inorganic materials directed by macromolecular self-assembly are
      expected to offer unique structural platforms relative to conventional porous
      inorganic materials. Their preparation to date remains a challenge, however,
      based on the sparsity of viable synthetic self-assembly pathways to control
      structural asymmetry. Here we demonstrate the fabrication of graded porous
      carbon, metal, and metal oxide film structures from self-assembled block
      copolymer templates by using various backfilling techniques in combination with
      thermal treatments for template removal and chemical transformations. The
      asymmetric inorganic structures display mesopores in the film top layers and a
      gradual pore size increase along the film normal in the macroporous sponge-like
      support structure. Substructure walls between macropores are themselves
      mesoporous, constituting a structural hierarchy in addition to the pore
      gradation. Final graded structures can be tailored by tuning casting conditions
      of self-assembled templates as well as the backfilling processes. We expect that
      these graded porous inorganic materials may find use in applications including
      separation, catalysis, biomedical implants, and energy conversion and storage. 

PMID- 25758194
TI  - Adenoid hypertrophy in children with allergic disease and influential factors.
AB  - OBJECTIVES: Adenoid hypertrophy (AH) may cause several comorbid conditions
      including sleep apnea, chronic serous otitis and sinusitis. Such conditions are
      more common among children with allergic diseases. In our study, we aimed to
      determine the patient profile associated with higher incidence of adenoid
      hypertrophy and the related influential factors. METHODS: The study included 1322
      children being treated and followed up for allergic conditions. 100 children with
      no allergic diseases presenting during the same period to the clinic were
      included as the control group. Skin prick test for the same allergens was
      performed for all patients. Adenoid tissue was analyzed by an ENT specialist and
      the diagnosis was confirmed based on the patient history, endoscopic physical
      examination and radiology. RESULTS: Of the patients, 765 (57.9%) were males and
      557 (42.1%) were females and their mean age was 5.9+/-3.3 years. In the control
      group, 56 (56%) children were males and 44 (44%) were females and their mean age
      was 6.3+/-4.1 years. Children with allergic disease and control subjects did not
      differ significantly by age and gender. Adenoid hypertrophy was identified in 164
      (12.4%) of the patients with allergic disease and in 3 (3%) of the controls.
      Allergic children were divided into two groups, as children with and without AH,
      respectively. The groups did not differ statistically significantly by gender,
      age or familial history of atopic disease. However, cigarette smoke exposure at
      home and presence of allergic rhinitis was significantly more frequent in the
      group of patients with AH. In the logistic model investigating the effect of
      variables on AH presence (according to age, gender, cigarette smoke exposure,
      asthma, AR, AD presence, atopy presence, sensitivity to house dust, pollen,
      epithelium, Alternaria alternata and cockroach), AR presence and cigarette smoke
      exposure were statistically significant. CONLUSIONS: AH frequency is higher in
      children with allergic disease compared to controls. The most common sensitivity
      to allergens among patients with AH was to house dust. Presence of allergic
      rhinitis and cigarette smoke exposure are risk factors for developing AH.
      Children with these risk factors should be questioned for AH during their routine
      examinations.

PMID- 25758195
TI  - Response to the Letter to the editor regarding "The 70-degree telescope as a
      teaching tool for cleft palate repair and pharyngoplasty surgery".

PMID- 25758196
TI  - Neonatal hearing screening: what we have achieved and what needs to be improved.
AB  - OBJECTIVE: To review the literature on neonatal hearing screening and its
      weaknesses with regard to missed follow-ups and delayed diagnosis and management.
      RESULTS: The implementation of newborn hearing screening programs has indeed
      lowered the mean age of hearing loss identification and many deaf children are
      now diagnosed at an early age of some months. However, the present collection of
      32 studies published in the International Journal of Pediatric
      Otorhinolaryngology revealed that late-onset deafness, auditory neuropathy, and
      the alarming percentage of newborns who fail the initial testing and then are
      lost to follow-up are major weaknesses of neonatal hearing screening programs. It
      seems that parents may be satisfied of hearing screening but in a significant
      percentage of them do not bring their children for follow-up or further testing
      due to phycho-social or other reasons. In addition, the same collection revealed
      that socioeconomic factors may have a significant influence on the effectiveness
      of hearing screening programs in the developed and developing countries, where
      improvements in health care politics, tracking system and public awareness is
      crucial for successful program implementation. CONCLUSIONS: Neonatal hearing
      screening programs have changed the whole picture of congenital deafness as age
      identification has significantly fallen with a very positive effect on timely
      management. However, the selected and proposed 32 related articles published in
      the International Journal of Pediatric Otorhinolaryngology show that there are
      still serious weakness in the neonatal hearing screening that need improvements
      in order to achieve an efficient and cost-effective system of deafness
      identification.

PMID- 25758197
TI  - The validity of family history as a risk factor in pediatric hearing loss.
AB  - OBJECTIVES: A family history of permanent childhood hearing loss is considered a
      risk factor for pediatric hearing loss, although its validity has been sparsely
      examined. This study aimed to: (1) investigate the prevalence and yield of this
      risk factor for congenital and postnatal hearing losses, (2) define the
      audiometric characteristics of hearing loss in children with positive family
      histories, and (3) assess the nature of the familial relationships. METHOD: A
      retrospective cohort study including all children born in Queensland, Australia
      between September 2004 and December 2011 who had completed Healthy Hearing's
      newborn hearing screen (n=380,895). RESULTS: (1) Prevalence of the risk factor
      was 1.09% (4138/380,895). Prevalence of the risk factor in congenital cases was
      7.29% and in postnatal cases was 36.84%. A low yield was identified for both
      congenital and postnatal groups (1.43% and 1.7%, respectively). (2) The degree of
      loss in congenital cases was highly varied, whereas the predominant degree in
      postnatal cases was mild. The most frequent type of loss for congenital cases was
      sensorineural, whereas for postnatal cases it was conductive. (3) Maternal or
      sibling relationships were most commonly reported for congenital losses, and
      maternal or paternal relationships for postnatal losses. CONCLUSIONS: Children
      with a family history of pediatric hearing loss should have their hearing
      screened at birth and be monitored throughout early childhood. However, more
      efficient surveillance methods should be considered in view of the high
      prevalence with low yield.

PMID- 25758198
TI  - Retrospective analysis of tympanoplasty in children with cleft palate: a 24-year
      experience. II. Cholesteatomatous cases.
AB  - BACKGROUND: Contradictory experience has been published on the outcomes of ear
      surgery in patients with cleft palate. OBJECTIVES: The authors of this study
      investigated whether there were differences in the short- and long-term outcomes
      of tympanoplasty performed due to cholesteatoma in children with or without cleft
      palate. SETTING: Tertiary care medical centre. METHODS: The authors
      retrospectively analyzed the first author's 24-year experience of paediatric
      tympanoplasty using the software programme developed by the fourth author. The
      outcomes of 268 tympanoplasties on 172 ears with cholesteatoma in 151 'NoCleft'
      patients were compared to the outcomes of 35 tympanoplasties on 20 ears of 19
      'Cleft' patients. The average age of the patients was 10.7+/-3.6 years and 9.5+/
      2.7 years respectively. The average follow-up time was 4 and 4.1 years. RESULTS:
      Preoperative PTA-ABGs (31.22/34.88 dB; p=0.058), best postoperative PTA-ABGs
      (17.04/16.4 dB; p=0.499), last postoperative PTA-ABGs (19.93/20.98 dB; p=0.298),
      the final hearing improvement (11.29/13.9 dB; p=0.193) and postoperative PTA-ABG
      deterioration with time (2.89/4.58 dB; p=0.117) were statistically compared
      between the 'NoCleft' and 'Cleft' groups. The same parameters were analyzed
      separately in the case of tympanoplasty performed with intact ossicular chain and
      the different type of columella ossiculoplasty. No significant differences were
      found between the two groups in any of these parameters. However, significant
      difference was found in the necessity for grommet insertion (8-fold difference,
      p~0), and conversion to open techniques (p~0). CONCLUSIONS: The authors conclude
      that the achievable audiological outcomes of tympanoplasty in children with cleft
      palate and cholesteatoma do not differ significantly from those of the general
      child population. However, this more frequently requires ventilation tube
      insertion and more frequent follow-up visits. The latter is ensured by patient
      care within the frameworks of the 'Cleft Palate Team'. We have to accept that in
      some cases Eustachian tube dysfunction caused by the underlying disease (cleft
      palate) 'takes over' and we have to resort to open techniques.

PMID- 25758199
TI  - Long term outcome of cochlear implantation in five children with common cavity
      deformity.
AB  - INTRODUCTION: A common cavity (CC) deformity is a deformed inner ear in which the
      cochlea and vestibule are confluent forming a common rudimentary cystic cavity.
      The outcome of cochlear implantation (CI) in this deformity is not expected as
      good as in other cochlear deformity. Categories of Auditory Performance (CAP)
      score, Speech Intelligibility Rating (SIR) scale, Meaningful Auditory-Integration
      Scale (MAIS) and Meaningful Use of Speech Scale (MUSS) are scales designed to
      assess benefit of functional device (hearing aid, Cochlear implant, ABI) in young
      children. The aim of the study was to observe and report the long-term
      audiological progress and speech development of children with CC deformity after
      CI by means of CAP, SIR, MAIS, MUSS scores and CI aided threshold. METHODS AND
      MATERIALS: The retrospective and prospective study was carried out in five Indian
      children with CC deformity who underwent CI from 2004 to 2010. Demographic data
      of onset and/or duration of deafness, age at implantation, time with hearing aids
      before implantation, duration with CI and co-morbidity were retrieved from a
      local data base. Their outcome score in audition and speech development on the
      basis of their CAP and SIR score at the end of 1 year of habilitation were
      collected. All the patients were called to follow up to obtain latest CI aided
      audiogram, CAP, SIR, MAIS and MUSS scores. RESULTS: One male and four female
      children were detected with common cavity deformity among 258 deaf children of
      age below 6 years operated during study period. The CAP and SIR Scores increased
      from average of 0.4 and 1 to 3.4 and 2.4, respectively, over one year of
      habilitation. The CAP score improved in subsequent follow up to average of 5.0
      after more than 3 years of follow up but the SIR score hardly improved. We
      assessed the MAIS and MUSS at last visit after 3 years. The mean of MAIS and MUSS
      was 32.4 and 26.4, respectively. CONCLUSION: Though the habilitation outcome was
      not up to the mark in children with CC deformity, CI provides excellent awareness
      of environment sound and development of few words.

PMID- 25758200
TI  - Increased expression of formin-like 3 contributes to metastasis and poor
      prognosis in colorectal carcinoma.
AB  - Formin-like 3 (FMNL3), a member of diaphanous-related formins subfamily, plays an
      important role in cytoskeleton reorganization, cell adhesion and cancer cell
      invasion in vitro. This study aimed to explore the expression of FMNL3 in
      colorectal carcinoma (CRC) cell-lines and tissues, and further evaluate its
      prognostic value and correlation with the clinicopathological parameters, and
      also investigate the effects of FMNL3 gene silencing on the growth and metastasis
      of CRC in vivo. Immunohistochemical analysis showed that FMNL3 protein was
      distributed in a punctuate aggregation pattern and located mainly in the
      cytoplasm of glandular cavity side, close to the nucleus of CRC cells. The
      positive rate of FMNL3 expression was 87.5% (84/96) in CRC, which was
      significantly higher than that in adjacent normal mucosa (30%, 9/30). Moreover,
      FMNL3 protein expressed far more in primary CRC with metastasis and corresponding
      lymph nodes metastatic CRC than in primary CRC without metastasis. Increased
      expression of FMNL3 was closely correlated with tumor size, differentiation,
      serosal invasion, and both lymph node metastasis and distant metastasis. However,
      it was not correlated with patients' age and gender. According to Kaplan-Meier
      survival analyses, patients with FMNL3 high expression level had lower overall
      survival rate than that with FMNL3 low expression level. Univariate and
      multivariate analyses revealed that high FMNL3 expression was a significant and
      independent prognostic predictor of patients with CRC. In addition, FMNL3 mRNA
      and protein levels were substantially up-regulated in CRC-metastasis-derived cell
      lines, as compared to those in primary-CRC-derived ones. FMNL3 gene silencing
      suppressed the growth and metastasis of CRC in vivo. In conclusion, FMNL3 plays
      an important role in the progression and metastasis of CRC and may be a novel
      potential prognostic predictor and therapeutic target for patients with CRC. 

PMID- 25758201
TI  - Analysis of glial fibrillary acidic protein (GFAP)-expressing ductular cells in a
      rat liver cirrhosis model induced by repeated injections of thioacetamide (TAA).
AB  - Glial fibrillary acidic protein (GFAP), a type III intermediate filament protein,
      is expressed in hepatic stellate cells (HSCs), the principal fibrogenic cell type
      in the liver. Further, GFAP could be a marker for hepatic progenitor cells
      (HPCs). In this study, the participation of GFAP-expressing cells in HPC
      expansion/ductular reaction was investigated in a rat model of liver cirrhosis.
      Six-week-old male F344 rats were injected intraperitoneally with thioacetamide
      (100mg/kg BW, twice a week) and examined at post-first injection weeks 5, 10, 15,
      20 and 25. Fibrosis-related proliferation of ductular cells was observed as
      demonstrated by CK19 immunostaining. Some of these cells were stained with GFAP.
      No co-staining was observed between CK19 and alpha-smooth muscle actin (alpha
      SMA; myofibroblast marker). There were proliferating ductular cells stained with
      alpha-fetoprotein or beta-catenin; the ductular reaction was related to increased
      expression of hepatocarcinogenesis-related factors (Wnt2, Wnt4 and glypican-3).
      These results for the first time show the participation of GFAP-positive HPCs in
      ductular reaction in a chemically induced rodent model. Though the ductular cells
      were chaperoned by myofibroblasts, they show no direct evidence for epithelial to
      mesenchymal transition. These findings shed new light in understanding the roles
      of GFAP-expressing HPCs in liver cirrhosis and provide further evidence of
      interaction between newly-formed bile ductules and HSCs, suggesting that both
      cells could be in the common lineage of HPCs. 

PMID- 25758203
TI  - Genomic characterization of endometrial stromal sarcomas with array comparative
      genomic hybridization.
AB  - INTRODUCTION: The endometrial stromal sarcoma (ESS) is a very rare uterine
      sarcoma, counting for 1-3% of all gynecologic malignancies. ESS represents 0.2-8%
      of all uterine malignant tumors and accounts for about 10% of all uterine
      sarcomas. With regard to chromosomal aberrations, very little is known about
      benign and malignant endometrial stromal tumors. METHODS: 30 tumors, consisting
      of 4 cases of benign endometrial stromal nodule (ESN), 22 cases of low-grade ESS
      and 4 cases of undifferentiated endometrial sarcoma (UES), were analyzed by array
      comparative genomic hybridization (aCGH). RESULTS: ESN did not show many copy
      number changes (CNCs) by aCGH. Frequent losses could be identified on chromosomes
      7p and 19, and gains on chromosomes 1q, 6p and 8q. Low-grade ESS presented as a
      very heterogeneous group. 90% (20/22) of cases displayed aberrations. Most
      frequent changes were losses on chromosomes 7 and 22, and gains on chromosome 1q
      or 11. UES showed a high number of chromosomal aberrations and on every
      chromosome CNCs were detected. Most frequent changes were losses on chromosomes
      1q, 2q (3/4, 75%) and 13, and gains on chromosomes 1q and 17p. CONCLUSION: Our
      data shows an increasing number of CNCs from ESN to low-grade ESS and to UES.
      However, the chromosomal aberrations differ considerably between the investigated
      ESN-, low-grade ESS- and UES cases and thus, a linear tumor progression seems to
      be unlikely.

PMID- 25758202
TI  - How to prevent alcoholic liver disease.
AB  - Betaine supplements of alcoholic beverages are proposed to prevent the
      development of alcoholic liver disease in patients that abuse alcohol. This
      recommendation is based on the observation of studies where it has been shown in
      binge drinking and chronic ethanol feeding animal models that betaine prevents
      liver injury resulting from high blood alcohol levels. The basic observation is
      that betaine added to ethanol being ingested increases the elimination rate of
      blood alcohol, which prevents the blood alcohol levels (BALs) from reaching high
      levels. The mechanism of how betaine does this is postulated to be that betaine
      causes the increase in the elimination rate by increasing the metabolic rate
      which generates NAD the rate limiting cofactor of alcohol oxidation by ADH.
      Betaine does this most likely by supporting the methylation of norepinephrine to
      form epinephrine by phenylethanolamine N-methyltransferase. Epinephrine is 5 to
      10-fold more active than norepinephrine in increasing the metabolic rate. 

PMID- 25758204
TI  - Microsolvation of LiBO2 in water: anion photoelectron spectroscopy and ab initio
      calculations.
AB  - The microsolvation of LiBO2 in water was investigated by conducting anion
      photoelectron spectroscopy and ab initio studies on the LiBO2(H2O)n(-) (n = 0-5)
      clusters. By comparing calculations with experiments, the structures of these
      clusters and their corresponding neutrals were assigned, and their structural
      evolutions were revealed. During the anionic structural evolution with n
      increasing to 5, hydroxyborate and metaborate channels were identified and the
      metaborate channel is more favorable. For the hydroxyborate structures, the
      anionic Li(+)-BO2(-) ion pair reacts with a water molecule to produce the
      LiBO(OH)2(-) moiety and three water molecules tend to dissolve this moiety. In
      the metaborate channel, two types of solvent-separated ion pair (SSIP) geometries
      were determined as the ring-type and linear-type. The transition from the contact
      ion pair (CIP) to the ring-type of SSIP starts at n = 3, while that to the linear
      type of SSIP occurs at n = 4. In neutral LiBO2(H2O)n clusters, the first water
      molecule prefers to react with the Li(+)-BO2(-) ion pair to generate the
      LiBO(OH)2 moiety, analogous to the bulk crystal phase of alpha-LiBO2 with two O
      atoms substituted by two OH groups. The Li-O distance in the LiBO(OH)2 moiety
      increases with the increasing number of water molecules and elongates abruptly at
      n = 4. Our studies provide new insight into the initial dissolution of LiBO2 salt
      in water at the molecular level and may be correlated to the bulk state. 

PMID- 25758205
TI  - Are interactions between organic compounds and nanoscale weathering minerals the
      key drivers of carbon storage in soils?

PMID- 25758206
TI  - Canine filarial infections in Liguria, north-west Italy.
AB  - This paper reports the findings of a study on the presence of various species of
      filarial nematodes in dogs in Liguria, north-west Italy, a region traditionally
      considered free from the disease. Between 2009 and 2012 blood samples were taken
      from 365 dogs in rural areas in Liguria. The blood samples were then submitted to
      Knott's test, histochemical staining, polymerase chain reaction (PCR) and the
      enzyme-linked immunosorbent assay (ELISA) for Dirofilaria immitis antigens.
      Overall, 35 of the 365 dogs were positive using Knott's test for microfilariae
      (prevalence 9.6%; 95% confidence interval (CI): 6.6-12.6%). Acanthocheilonema
      reconditum was the most prevalent species (8.0%), while Dirofilaria repens (1.4%)
      and Dirofilaria immitis (0.6%) were less common. One co-infection by D. repens
      and A. reconditum was observed. All morphological identifications were confirmed
      by histochemical staining and PCR. In addition, a retrospective analysis of data
      on D. immitis antigens in 11,363 samples of canine sera was carried out. Sera
      were collected and analysed for D. immitis antigens by the Istituto
      Zooprofilattico Sperimentale (IZS) of Piedmont, Liguria and Aosta Valley (Imperia
      section) between 2004 and 2013 during annual tests for leishmaniasis on
      autochthonous dogs throughout Liguria. Serological data from IZS showed an
      overall seroprevalence of 0.65% (95% CI: 0.50-0.80%) for D. immitis throughout
      the region. The present study updates the epidemiological map of canine filarial
      infections in Italy and suggests the need for surveillance and prophylaxis in
      Liguria. 

PMID- 25758207
TI  - Refractory cardiogenic shock in a patient with beta-thalassemia major requiring
      mechanical circulatory support: Case report and literature review.
AB  - Iron overload cardiomyopathy secondary to beta-thalassemia major is a potentially
      reversible condition managed with chelation and medical hemodynamic support, as
      bridge-to-recovery or transplant. We describe our experience, and challenges
      faced, in a pediatric patient with iron overload cardiomyopathy secondary to beta
      thalassemia major, requiring biventricular MCS. 

PMID- 25758208
TI  - The Glucosinolate Biosynthetic Gene AOP2 Mediates Feed-back Regulation of
      Jasmonic Acid Signaling in Arabidopsis.
AB  - Survival in changing and challenging environments requires an organism to
      efficiently obtain and use its resources. Due to their sessile nature, it is
      particularly critical for plants to dynamically optimize their metabolism. In
      plant primary metabolism, metabolic fine-tuning involves feed-back mechanisms
      whereby the output of a pathway controls its input to generate a precise and
      robust response to environmental changes. By contrast, few studies have addressed
      the potential for feed-back regulation of secondary metabolism. In Arabidopsis,
      accumulation of the defense compounds glucosinolates has previously been linked
      to genetic variation in the glucosinolate biosynthetic gene AOP2. AOP2 expression
      can increase the transcript levels of two known regulators (MYB28 and MYB29) of
      the pathway, suggesting that AOP2 plays a role in positive feed-back regulation
      controlling glucosinolate biosynthesis. We generated mutants affecting AOP2,
      MYB28/29, or both. Transcriptome analysis of these mutants identified a so far
      unrecognized link between AOP2 and jasmonic acid (JA) signaling independent of
      MYB28 and MYB29. Thus, AOP2 is part of a regulatory feed-back loop linking
      glucosinolate biosynthesis and JA signaling and thereby allows the glucosinolate
      pathway to influence JA sensitivity. The discovery of this regulatory feed-back
      loop provides insight into how plants optimize the use of resources for defensive
      metabolites. 

PMID- 25758209
TI  - Graft-induced dyskinesias fail to respond to 5HT1A agonist in the long-term.

PMID- 25758210
TI  - Impact of injected dose and acquisition time on a normal database by use of 3D
      SSP in SPECT images: quantitative simulation studies.
AB  - The present study aimed to validate the accuracy of normal databases (NDBs) with
      respect to variable injected doses and acquisition times by use of three
      dimensional stereotactic surface projections (3D-SSP) in N-isopropyl-p-[123I]
      iodoamphetamine (I-123-IMP) brain perfusion images. We constructed NDBs based on
      brain SPECT images obtained from 29 healthy volunteers. Each NDB was rebuilt
      under simulated unique conditions by use of dynamic acquisition datasets and
      comprised injected doses (222, 167, and 111 MBq) and acquisition times (30, 20,
      and 15 min). We selected seven of 29 datasets derived from the volunteers to
      simulate patients' data (PD). The simulated PD were designed to include regions
      of hypoperfusion. The study comprised protocol A (same conditions for PD and NDB)
      and protocol B (mismatched conditions for PD and NDB). We used 3D-SSP to compare
      with the Z score and detection error. The average Z scores were decreased
      significantly in protocol A [PD (High)-NDB (High) vs. PD (Low)-NDB (Low); PD (30
      m)-NDB (30 m) vs. PD (15 m)-NDB (15 m) and PD (20 m)-NDB (20 m)].The average Z
      scores of PD (High) and PD (Medium) with NDB (High) did not differ significantly
      in protocol B, whereas all others were decreased significantly. The error of
      detection increased 6.65 % (protocol A) and 32.05 % (protocol B). The Z scores
      were specific to the injected dose and acquisition time used in 3D-SSP studies,
      and the calculated Z scores were affected by mismatched injected doses and
      acquisition times between PD and selected NDBs. 

PMID- 25758211
TI  - Former male elite athletes have better metabolic health in late life than their
      controls.
AB  - Elite-class athletes have longer life expectancy and lower risk for chronic
      noncommunicable diseases possibly because of physically active and healthier
      lifestyle. In this study, we assessed former male Finnish elite-class athletes'
      (n = 392) and their matched controls' (n = 207) body composition, and risk for
      the metabolic syndrome (MS) and nonalcoholic fatty liver disease (NAFLD) in later
      life. Compared with the controls, the former athletes had lower body fat
      percentage (24.8% vs 26.0%, P = 0.021), lower risk for MS [odds ratio (OR) 0.57,
      95% confidence interval (CI) 0.40-0.81], and NAFLD (OR 0.61, 95% CI 0.42-0.88).
      High volume of current leisure-time physical activity (LTPA) was associated with
      lower body fat percentage (P for trend < 0.001). When current volume of LTPA
      increased 1 MET h/week, the risk of MS and NAFLD decreased (OR 0.99, 95% CI 0.98
      0.99 and OR 0.97, 95% CI 0.96-0.98, respectively). Although a career as an elite
      class athlete during young adulthood may help to protect from developing
      metabolic syndrome, present exercise levels and volume of LTPA seem equally
      important as well.

PMID- 25758212
TI  - Methodological issues in estimating sodium intake in the Korea National Health
      and Nutrition Examination Survey.
AB  - For policy goal setting, efficacy evaluations, and the development of related
      programs for reducing sodium intake, it is essential to accurately identify the
      amount of sodium intake in South Korea and constantly monitor its trends. The
      present study aimed to identify the status of sodium intake in South Korea and to
      review the methods and their validity for estimating sodium intake in each
      country; through this, we aim to determine more accurate methods for determining
      sodium intake and to monitor the trend in sodium intake for Korean citizens in
      the future. Using 24-hour dietary recall data from the 2012 Korea National Health
      and Nutrition Examination Survey (KNHANES) to estimate daily sodium intake, the
      average daily sodium intake among Koreans was 4,546 mg (men, 5,212 mg; women,
      3,868 mg). In addition to the nutrition survey that uses the 24-hour dietary
      recall method, sodium intake can also be calculated from the amount of sodium
      excreted in 24-hour urine, 8-hour overnight urine, and spot urine samples.
      Although KNHANES uses the 24-hour dietary recall method to estimate the sodium
      intake, the 24-hour dietary recall method has the disadvantage of not being able
      to accurately determine the amount of sodium intake owing to its unique
      characteristics of the research method and in the processing of data. Although
      measuring the amount of sodium excreted in 24-hour urine is known to be the most
      accurate method, because collecting 24-hour urine from the general population is
      difficult, using spot urine samples to estimate sodium intake has been suggested
      to be useful for examining the trend of sodium intake in the general population.
      Therefore, we planned to conduct a study for estimating of 24-hour sodium
      excretion from spot urine and 8-hour overnight urine samples and testing the
      validity among subsamples in the KNHANES. Based on this result, we will adopt the
      most appropriate urine collection method for estimating population sodium intake
      in South Korea. 

PMID- 25758213
TI  - The effect of community-level smoke-free ordinances on smoking rates in men based
      on Community Health Surveys.
AB  - OBJECTIVES: As one of smoke-free policies, communities have established the smoke
      free ordinances since August 2010. Thus, this study aimed to evaluate the effects
      of community-level smoke-free ordinances (SFO) on smoking rates in men using
      multiyear Community Health Survey (CHS) data. METHODS: Data on community-level
      SFO were collected from a website on Enhanced Local Laws and Regulation
      Information System. Regional smoking-related data were obtained from CHS data
      from 2008 to 2012 and the age-standardized rates of current smoking in men,
      attempts to quit smoking, and smoke-free campaign experiences including the mean
      number of cigarettes smoked (smoking amount) were calculated. Repeated measures
      analysis of variance was performed to evaluate the effects of regional
      implementation of SFO and the duration on change of smoking rates. RESULTS:
      Overall current smoking rates and daily mean cigarettes smoked were lower in
      community where SFO had been implemented compared to those without
      implementation, and there was a significant difference in smoking rates between
      2010 and 2008. Cross-sectional analysis of the effects of regional SFO revealed
      clear difference in rate of current smoking, but longitudinal analysis showed no
      significant differences. Stratifying by age groups, however, showed that groups
      less than 30 years of age had low smoking rates in community with ordinance
      compared to those without SFO since 2010. Yearly surveys measuring the number of
      cigarettes smoked, attempts to quit smoking, and experiences of smoke-free
      campaigns showed regional differences in the duration of implementation, but
      these differences were not significant in longitudinal analysis. Furthermore,
      there was a difference in regional socioeconomic characteristics between
      community with and without SFO implementation. CONCLUSIONS: For effective smoking
      control, it is necessary to evaluate current policies and develop indices to
      evaluate the practical implementation of ordinances. As more communities to pass
      the SFO, long-term observation and assessments required.

PMID- 25758214
TI  - Negative affect is associated with development and persistence of chemical
      intolerance: a prospective population-based study.
AB  - OBJECTIVE: Chemical intolerance (CI) is characterised by negative health effects
      attributed to a heightened responsiveness to common airborne chemicals. This
      longitudinal study explored the hypothesised role of negative affect in the
      development and persistence of CI in a general population. METHODS: A general
      population sample aged 19 to 72 years was examined in 2006-2008 and again in 2011
      2012. Longitudinal data on CI were analysed with the purpose of examining
      baseline negative affect as a risk factor for having developed CI at 5-year
      follow-up and for reporting persistent CI. Participants were classified as
      reporting no signs of CI, having symptoms of CI and as being a likely CI case
      based on self-reported reactions to 11 common chemical exposures, symptoms
      related to chemical exposures and daily life adjustments attributed to reactions
      when exposed to chemicals. RESULTS: A total of 69.4% of the participants who had
      reported CI at baseline also reported CI at follow-up. In participants with no
      baseline CI, 15.5% reported CI at follow-up and 18.1% reported symptoms related
      to chemicals but no daily life adjustments. Baseline negative affect was
      positively and statistically significantly associated with both development and
      persistence of CI. CONCLUSIONS: Initial reports of CI were found to be persistent
      over time, and a considerable proportion of the participants with no CI at
      baseline reported having developed CI after 5 years. The positive association
      between negative affect and CI at the 5-year follow-up supports negative affect
      as a possible risk factor for CI.

PMID- 25758215
TI  - Anterior cruciate ligament- and hamstring tendon-derived cells: in vitro
      differential properties of cells involved in ACL reconstruction.
AB  - Anterior cruciate ligament (ACL) reconstruction involves the replacement of the
      torn ligament with a new graft, often a hamstring tendon (HT). Described as
      similar, the ACL and HT have intrinsic differences related to their distinct
      anatomical locations. From a cellular perspective, identifying these differences
      represents a step forward in the search for new cues that enhance recovery after
      the reconstruction. The purpose of this study was to characterize the phenotype
      and multilineage potential of ACL- and HT-derived cells. ACL- and HT-derived
      cells were isolated from tissue harvest from patients undergoing total knee
      arthroplasty (TKA) or ACL reconstruction. In total, three ACL and three HT donors
      were investigated. Cell morphology, self-renewal potential (CFU-F), surface
      marker profiling, expression of tendon/ligament-related markers (PCR) and
      multilineage potential were analysed for both cell types; both had fibroblast
      like morphology and low self-renewal potential. No differences in the expression
      of tendon/ligament-related genes or a selected set of surface markers were
      observed between the two cell types. However, differences in their multilineage
      potential were observed: while ACL-derived cells showed a high potential to
      differentiate into chondrocytes and adipocytes, but not osteoblasts, HT-derived
      cells showed poor potential to form adipocytes, chondrocytes and osteoblasts. Our
      results demonstrated that HT-derived cells have low multilineage potential
      compared to ACL-derived cells, further highlighting the need for extrinsic
      signals to fully restore the function of the ACL upon reconstruction. Copyright
      (c) 2015 John Wiley & Sons, Ltd.

PMID- 25758216
TI  - Physical function, pain, quality of life and life satisfaction of amputees from
      the 2008 Sichuan earthquake: A prospective cohort study.
AB  - OBJECTIVES: To examine the development and determinants of long-term outcomes for
      earthquake victims with amputations, including physical function, pain, quality
      of life and life satisfaction. DESIGN: Prospective cohort study with 2-3
      measurement points. SUBJECTS: A total of 72 people who underwent amputations
      following the 2008 Sichuan Earthquake and resided in Mianzhu County, Sichuan
      Province, China were enrolled in the study. Of these, 27 people were lost to
      follow-up. METHODS: Data on pain (visual analogue scale) and physical function
      (Barthel Index) were collected at 3 measurement points (2009, 2010 and 2012), and
      data on quality of life (Medical Outcomes Short-Form 36) and life satisfaction
      (Life Satisfaction Questionnaire-11) were collected at 2 measurement points (2010
      and 2012). Data were analysed with mixed effects regression. RESULTS: Pain
      severity declined significantly and physical function increased by 2012. Quality
      of life and life satisfaction remained relatively stable between 2010 and 2012,
      while quality of life was significantly lower than reference values from the
      general population. Illiteracy and lower extremity amputations were associated
      with lower quality of life and life satisfaction in several domains. CONCLUSION:
      While amputees' functioning and pain were improved over time, quality of life and
      life satisfaction did not change. Illiterate earthquake survivors and those with
      lower extremity amputations are at particular risk of low quality of life and
      life satisfaction, and may require additional attention in future earthquake
      rehabilitation programs.

PMID- 25758218
TI  - Mammary gland development: cell fate specification, stem cells and the
      microenvironment.
AB  - The development of the mammary gland is unique: the final stages of development
      occur postnatally at puberty under the influence of hormonal cues. Furthermore,
      during the life of the female, the mammary gland can undergo many rounds of
      expansion and proliferation. The mammary gland thus provides an excellent model
      for studying the 'stem/progenitor' cells that allow this repeated expansion and
      renewal. In this Review, we provide an overview of the different cell types that
      constitute the mammary gland, and discuss how these cell types arise and
      differentiate. As cellular differentiation cannot occur without proper signals,
      we also describe how the tissue microenvironment influences mammary gland
      development. 

PMID- 25758217
TI  - Skeletal stem cells.
AB  - Skeletal stem cells (SSCs) reside in the postnatal bone marrow and give rise to
      cartilage, bone, hematopoiesis-supportive stroma and marrow adipocytes in defined
      in vivo assays. These lineages emerge in a specific sequence during embryonic
      development and post natal growth, and together comprise a continuous anatomical
      system, the bone-bone marrow organ. SSCs conjoin skeletal and hematopoietic
      physiology, and are a tool for understanding and ameliorating skeletal and
      hematopoietic disorders. Here and in the accompanying poster, we concisely
      discuss the biology of SSCs in the context of the development and postnatal
      physiology of skeletal lineages, to which their use in medicine must remain
      anchored. 

PMID- 25758219
TI  - Plant stem cell maintenance by transcriptional cross-regulation of related
      receptor kinases.
AB  - The CLAVATA3 (CLV3)-CLAVATA1 (CLV1) ligand-receptor kinase pair negatively
      regulates shoot stem cell proliferation in plants. clv1 null mutants are weaker
      in phenotype than clv3 mutants, but the clv1 null phenotype is enhanced by
      mutations in the related receptor kinases BARELY ANY MERISTEM 1, 2 and 3 (BAM1, 2
      and 3). The basis of this genetic redundancy is unknown. Here, we demonstrate
      that the apparent redundancy in the CLV1 clade is in fact due to the
      transcriptional repression of BAM genes by CLV1 signaling. CLV1 signaling in the
      rib meristem (RM) of the shoot apical meristem is necessary and sufficient for
      stem cell regulation. CLV3-CLV1 signaling in the RM represses BAM expression in
      wild-type Arabidopsis plants. In clv1 mutants, ectopic BAM expression in the RM
      partially complements the loss of CLV1. BAM regulation by CLV1 is distinct from
      CLV1 regulation of WUSCHEL, a proposed CLV1 target gene. In addition, quadruple
      receptor mutants are stronger in phenotype than clv3, pointing to the existence
      of additional CLV1/BAM ligands. These data provide an explanation for the genetic
      redundancy seen in the CLV1 clade and reveal a novel feedback operating in the
      control of plant stem cells. 

PMID- 25758220
TI  - Gata2b is a restricted early regulator of hemogenic endothelium in the zebrafish
      embryo.
AB  - The adult blood system is established by hematopoietic stem cells (HSCs), which
      arise during development from an endothelial-to-hematopoietic transition of cells
      comprising the floor of the dorsal aorta. Expression of aortic runx1 has served
      as an early marker of HSC commitment in the zebrafish embryo, but recent studies
      have suggested that HSC specification begins during the convergence of posterior
      lateral plate mesoderm (PLM), well before aorta formation and runx1
      transcription. Further understanding of the earliest stages of HSC specification
      necessitates an earlier marker of hemogenic endothelium. Studies in mice have
      suggested that GATA2 might function at early stages within hemogenic endothelium.
      Two orthologs of Gata2 exist in zebrafish: gata2a and gata2b. Here, we report
      that gata2b expression initiates during the convergence of PLM, becoming
      restricted to emerging HSCs. We observe Notch-dependent gata2b expression within
      the hemogenic subcompartment of the dorsal aorta that is in turn required to
      initiate runx1 expression. Our results indicate that Gata2b functions within
      hemogenic endothelium from an early stage, whereas Gata2a functions more broadly
      throughout the vascular system. 

PMID- 25758221
TI  - Maintenance of Drosophila germline stem cell sexual identity in oogenesis and
      tumorigenesis.
AB  - Adult stem cells maintain tissue homeostasis by balancing self-renewal and
      differentiation. In Drosophila females, germline stem cells (GSCs) require Sex
      lethal (Sxl) to exit the stem cell state and to enter the differentiation
      pathway. Without Sxl GSCs do not differentiate and instead form tumors. Previous
      studies have shown that these tumors are not caused by a failure in the self
      renewal/differentiation switch. Here, we show that Sxl is also necessary for the
      cell-autonomous maintenance of germ cell female identity and demonstrate that
      tumors are caused by the acquisition of male characteristics. Germ cells without
      Sxl protein exhibit a global derepression of testis genes, including Phf7, a male
      germline sexual identity gene. Phf7 is a key effector of the tumor-forming
      pathway, as it is both necessary and sufficient for tumor formation. In the
      absence of Sxl protein, inappropriate Phf7 expression drives tumor formation
      through a cell-autonomous mechanism that includes sex-inappropriate activation of
      Jak/Stat signaling. Remarkably, tumor formation requires a novel response to
      external signals emanating from the GSC niche, highlighting the importance of
      interactions between mutant cells and the surrounding normal cells that make up
      the tumor microenvironment. Derepression of testis genes, and inappropriate Phf7
      expression, is also observed in germ cell tumors arising from the loss of bag of
      marbles (bam), demonstrating that maintenance of female sexual identity requires
      the concerted actions of Sxl and bam. Our work reveals that GSCs must maintain
      their sexual identity as they are reprogrammed into a differentiated cell, or
      risk tumorigenesis. 

PMID- 25758222
TI  - Vitamin K reduces hypermineralisation in zebrafish models of PXE and GACI.
AB  - The mineralisation disorder pseudoxanthoma elasticum (PXE) is associated with
      mutations in the transporter protein ABCC6. Patients with PXE suffer from
      calcified lesions in the skin, eyes and vasculature, and PXE is related to a more
      severe vascular calcification syndrome called generalised arterial calcification
      of infancy (GACI). Mutations in ABCC6 are linked to reduced levels of circulating
      vitamin K. Here, we describe a mutation in the zebrafish (Danio rerio) orthologue
      abcc6a, which results in extensive hypermineralisation of the axial skeleton.
      Administration of vitamin K to embryos was sufficient to restore normal levels of
      mineralisation. Vitamin K also reduced ectopic mineralisation in a zebrafish
      model of GACI, and warfarin exacerbated the mineralisation phenotype in both
      mutant lines. These data suggest that vitamin K could be a beneficial treatment
      for human patients with PXE or GACI. Additionally, we found that abcc6a is
      strongly expressed at the site of mineralisation rather than the liver, as it is
      in mammals, which has significant implications for our understanding of the
      function of ABCC6. 

PMID- 25758223
TI  - A Grhl2-dependent gene network controls trophoblast branching morphogenesis.
AB  - Healthy placental development is essential for reproductive success; failure of
      the feto-maternal interface results in pre-eclampsia and intrauterine growth
      retardation. We found that grainyhead-like 2 (GRHL2), a CP2-type transcription
      factor, is highly expressed in chorionic trophoblast cells, including basal
      chorionic trophoblast (BCT) cells located at the chorioallantoic interface in
      murine placentas. Placentas from Grhl2-deficient mouse embryos displayed defects
      in BCT cell polarity and basement membrane integrity at the chorioallantoic
      interface, as well as a severe disruption of labyrinth branching morphogenesis.
      Selective Grhl2 inactivation only in epiblast-derived cells rescued all placental
      defects but phenocopied intraembryonic defects observed in global Grhl2
      deficiency, implying the importance of Grhl2 activity in trophectoderm-derived
      cells. ChIP-seq identified 5282 GRHL2 binding sites in placental tissue. By
      integrating these data with placental gene expression profiles, we identified
      direct and indirect Grhl2 targets and found a marked enrichment of GRHL2 binding
      adjacent to genes downregulated in Grhl2(-/-) placentas, which encoded known
      regulators of placental development and epithelial morphogenesis. These genes
      included that encoding the serine protease inhibitor Kunitz type 1 (Spint1),
      which regulates BCT cell integrity and labyrinth formation. In human placenta, we
      found that human orthologs of murine GRHL2 and its targets displayed co
      regulation and were expressed in trophoblast cells in a similar domain as in
      mouse placenta. Our data indicate that a conserved Grhl2-coordinated gene network
      controls trophoblast branching morphogenesis, thereby facilitating development of
      the site of feto-maternal exchange. This might have implications for syndromes
      related to placental dysfunction. 

PMID- 25758225
TI  - The serpin PN1 is a feedback regulator of FGF signaling in germ layer and primary
      axis formation.
AB  - Germ layer formation and primary axis development rely on Fibroblast growth
      factors (FGFs). In Xenopus, the secreted serine protease HtrA1 induces mesoderm
      and posterior trunk/tail structures by facilitating the spread of FGF signals.
      Here, we show that the serpin Protease nexin-1 (PN1) is transcriptionally
      activated by FGF signals, suppresses mesoderm and promotes head development in
      mRNA-injected embryos. An antisense morpholino oligonucleotide against PN1 has
      the opposite effect and inhibits ectodermal fate. However, ectoderm and anterior
      head structures can be restored in PN1-depleted embryos when HtrA1 and FGF
      receptor activities are diminished, indicating that FGF signals negatively
      regulate their formation. We show that PN1 binds to and inhibits HtrA1, prevents
      degradation of the proteoglycan Syndecan 4 and restricts paracrine FGF/Erk
      signaling. Our data suggest that PN1 is a negative-feedback regulator of FGF
      signaling and has important roles in ectoderm and head development. 

PMID- 25758224
TI  - Otolith tethering in the zebrafish otic vesicle requires Otogelin and alpha
      Tectorin.
AB  - Otoliths are biomineralised structures important for balance and hearing in fish.
      Their counterparts in the mammalian inner ear, otoconia, have a primarily
      vestibular function. Otoliths and otoconia form over sensory maculae and are
      attached to the otolithic membrane, a gelatinous extracellular matrix that
      provides a physical coupling between the otolith and the underlying sensory
      epithelium. In this study, we have identified two proteins required for otolith
      tethering in the zebrafish ear, and propose that there are at least two stages to
      this process: seeding and maintenance. The initial seeding step, in which otolith
      precursor particles tether directly to the tips of hair cell kinocilia, fails to
      occur in the einstein (eis) mutant. The gene disrupted in eis is otogelin (otog);
      mutations in the human OTOG gene have recently been identified as causative for
      deafness and vestibular dysfunction (DFNB18B). At later larval stages,
      maintenance of otolith tethering to the saccular macula is dependent on tectorin
      alpha (tecta) function, which is disrupted in the rolling stones (rst) mutant.
      alpha-Tectorin (Tecta) is a major constituent of the tectorial membrane in the
      mammalian cochlea. Mutations in the human TECTA gene can cause either dominant
      (DFNA8/12) or recessive (DFNB21) forms of deafness. Our findings indicate that
      the composition of extracellular otic membranes is highly conserved between
      mammals and fish, reinforcing the view that the zebrafish is an excellent model
      system for the study of deafness and vestibular disease. 

PMID- 25758226
TI  - Precise spatial restriction of BMP signaling is essential for articular cartilage
      differentiation.
AB  - The articular cartilage, which lines the joints of the limb skeleton, is distinct
      from the adjoining transient cartilage, and yet, it differentiates as a unique
      population within a contiguous cartilage element. Current literature suggests
      that articular cartilage and transient cartilage originate from different cell
      populations. Using a combination of lineage tracing and pulse-chase of actively
      proliferating chondrocytes, we here demonstrate that, similar to transient
      cartilage, embryonic articular cartilage cells also originate from the
      proliferating chondrocytes situated near the distal ends of skeletal anlagen. We
      show that nascent cartilage cells are capable of differentiating as articular or
      transient cartilage, depending on exposure to Wnt or BMP signaling, respectively.
      The spatial organization of the articular cartilage results from a band of Nog
      expressing cells, which insulates these proliferating chondrocytes from BMP
      signaling and allows them to differentiate as articular cartilage under the
      influence of Wnt signaling emanating from the interzone. Through experiments
      conducted in both chick and mouse embryos we have developed a model explaining
      simultaneous growth and differentiation of transient and articular cartilage in
      juxtaposed domains. 

PMID- 25758227
TI  - Histone deacetylase 1 and 2 regulate Wnt and p53 pathways in the ureteric bud
      epithelium.
AB  - Histone deacetylases (HDACs) regulate a broad range of biological processes
      through removal of acetyl groups from histones as well as non-histone proteins.
      Our previous studies showed that Hdac1 and Hdac2 are bound to promoters of key
      renal developmental regulators and that HDAC activity is required for embryonic
      kidney gene expression. However, the existence of many HDAC isoforms in embryonic
      kidneys raises questions concerning the possible specificity or redundancy of
      their functions. We report here that targeted deletion of both the Hdac1 and
      Hdac2 genes from the ureteric bud (UB) cell lineage of mice causes bilateral
      renal hypodysplasia. One copy of either Hdac1 or Hdac2 is sufficient to sustain
      normal renal development. In addition to defective cell proliferation and
      survival, genome-wide transcriptional profiling revealed that the canonical Wnt
      signaling pathway is specifically impaired in UB(Hdac1,2-/-) kidneys. Our results
      also demonstrate that loss of Hdac1 and Hdac2 in the UB epithelium leads to
      marked hyperacetylation of the tumor suppressor protein p53 on lysine 370, 379
      and 383; these post-translational modifications are known to boost p53 stability
      and transcriptional activity. Genetic deletion of p53 partially rescues the
      development of UB(Hdac1,2-/-) kidneys. Together, these data indicate that Hdac1
      and Hdac2 are crucial for kidney development. They perform redundant, yet
      essential, cell lineage-autonomous functions via p53-dependent and -independent
      pathways. 

PMID- 25758228
TI  - Staphylococcus aureus sepsis in rheumatoid arthritis.
AB  - Patients with rheumatoid arthritis (RA) are at increased risk of infection. In
      this study, we determined the risk of and risk factors for Staphyococcus aureus
      (S. aureus) sepsis in RA. We assembled a retrospective nested case-control subset
      of RA patients with S. aureus sepsis from the Barnes-Jewish Hospital Medical
      Informatics database, confirmed the diagnoses, and collected data electronically
      and by chart review. We used multivariate logistic regression to identify
      independent risk factors for S. aureus sepsis, with risk expressed as odds ratios
      (ORs). We extracted data on the length of hospitalization and 30-day and 1-year
      mortality from the Medical Informatics database for all cases and controls. There
      were 48 confirmed S. aureus sepsis cases and 232 confirmed controls in the RA
      cohort. In multivariate analysis, indwelling central venous catheter (OR 15.97;
      95 % CI 5.09-50.10; p < 0.01) and congestive heart failure (OR 2.89; 95 % CI 1.26
      6.63; p = 0.01) were independently associated with risk of S. aureus sepsis,
      while treatment with disease-modifying anti-rheumatic drugs (DMARDs), both
      biologic and non-biologic, was not. S. aureus sepsis was associated with
      increased 30-day and 1-year mortality (OR 7.37; 95 % CI 2.86-19.0; p < 0.01 for
      30-day and OR 5.24; 95 % CI 2.51-10.94; p < 0.01 for 1-year mortality) and longer
      hospitalization (p < 0.01). Treatment with biologic DMARDs was not associated
      with longer hospitalization (p = 0.89). Indwelling central venous catheters and
      congestive heart failure increased the risk of S. aureus sepsis in this
      observational cohort of patients with RA. Treatment with biologic and non
      biologic DMARDs did not increase this risk.

PMID- 25758229
TI  - Histopathological indicators of disease outcome in class IV lupus nephritis: a
      revisit of various indices.
AB  - Current management guidelines for lupus nephritis (LN) do not attach importance
      to histological indices of disease activity or chronicity. The present study was
      performed to evaluate the clinical relevance of these indices in determining
      outcomes in patients with class IV LN. We analyzed the data of all patients with
      biopsy-proven class IV LN seen over a 6-year period. The histopathological
      findings were reviewed; the activity and chronicity indices proposed by Austin
      [AI (Austin) & CI (Austin)] and the renal biopsy index proposed by Hill were
      calculated. As immunofluorescence was not done in all patients, this was excluded
      from calculation of the renal biopsy index, which was referred to as the modified
      Hill's index (MHI), which was a composite of glomerular activity index (GAI),
      chronicity index (CI) and tubulo-interstitial activity index (TIAI). Pearson's
      correlation coefficient, multilinear regression analysis and logistic analysis
      were performed, and p value of <.05 was considered significant. During the study
      period, 114 cases of LN were evaluated, of which 64 % (73/114) had class IV LN.
      The mean age was 26.5 years, and 92 % were females. The mean scores of AI
      (Austin), CI (Austin), GAI, CI, TIAI and MHI were 8.46, 2.50, 7.54, 3.06, 4.74
      and 2.23, respectively. Serum creatinine correlated significantly with TIAI, CI,
      CI (Austin) as well as MHI, but not with AI (Austin) or GAI. The serum creatinine
      level was the strongest clinical parameter determining outcome, while none of the
      histological indices correlated with either treatment outcome or mortality. None
      of the histological indices performed better than serum creatinine level in
      determining the treatment outcomes and mortality.

PMID- 25758231
TI  - Holes in the Nuclear Membrane as an Illustration of Gaps in the Understanding of
      the Biology by Biologists.
AB  - At the moment, the conditions are in place to describe how to construct nuclear
      pores and how they work, missing only real understanding of process. The DNA-RNA
      protein paradigm proposed by Crick 53 years ago (Symp Soc Exp Biol 12:138-163,
      1958; Nature 227:561-563, 1970) severely hampers our understanding of nuclear
      pore structure and assembly because the problem lies outside paradigm. DNA in
      this scheme only plays the role of information storage from which information is
      transferred to RNA, then from RNA to proteins after which proteins perform all of
      the functions in the cell. Although it is known that DNA is able to build
      nucleosomes in vivo, many in vitro structures types of origami (Rothemund, Nature
      440:297-302, 2006), the DNA is considered to be exotic as structural material for
      cells. The structural role of RNA is difficult to ignore, in connections with
      their participation in structures of ribosomes, ribonucleoproteins, and
      ribozymes, but imagine that DNA performs an important structural role in the cell
      is impossible in opinion of many authors. So, when there was a problem in
      explaining the origin of the nuclear pore, all efforts of biologists were
      directed to proteins such as nucleoporins, especially when taking into account
      that there are 30 nucleoporins and only one DNA. Here, I try to explain the
      typical mistakes of the old approach to such a complex problem as nuclear pore
      structure and assembly.

PMID- 25758230
TI  - Spectroscopic and Microscopic Studies on the Mechanism of Mitochondrial Toxicity
      Induced by CdTe QDs Modified with Different Ligands.
AB  - Quantum dots (QDs) are increasingly applied in sensing, drug delivery, biomedical
      imaging, electronics industries, etc. Consequently, it is urgently required to
      examine their potential threat to humans and the environment. In the present
      work, the toxicity of CdTe QDs with nearly identical maximum emission wavelength
      but modified with two different ligands (MPA and BSA) to mitochondria was
      investigated using flow cytometry, spectroscopic, and microscopic methods. The
      results showed that QDs induced mitochondrial permeability transition (MPT),
      which resulted in mitochondrial swelling, collapse of the membrane potential,
      inner membrane permeability to H(+) and K(+), the increase of membrane fluidity,
      depression of respiration, alterations of ultrastructure, and the release of
      cytochrome c. Furthermore, the protective effects of CsA and EDTA confirmed QDs
      might be able to induce MPT via a Ca(2+)-dependent domain. However, the
      difference between the influence of CdTe QDs and that of Cd(2+) on mitochondrial
      membrane fluidity indicated the release of Cd(2+) was not the sole reason that
      QDs induced mitochondrial dysfunction, which might be related to the nanoscale
      effect of QDs. Compared with MPA-CdTe QDs, BSA-CdTe QDs had a greater effect on
      the mitochondrial swelling, membrane fluidity, and permeabilization to H(+) and
      K(+) by mitochondrial inner membrane, which was caused the fact that BSA was more
      lipophilic than MPA. This study provides an important basis for understanding the
      mechanism of the toxicity of CdTe QDs to mitochondria, and valuable information
      for safe use of QDs in the future. 

PMID- 25758232
TI  - Performance modulation of alpha-MnO2 nanowires by crystal facet engineering.
AB  - Modulation of material physical and chemical properties through selective surface
      engineering is currently one of the most active research fields, aimed at
      optimizing functional performance for applications. The activity of exposed
      crystal planes determines the catalytic, sensory, photocatalytic, and
      electrochemical behavior of a material. In the research on nanomagnets, it opens
      up new perspectives in the fields of nanoelectronics, spintronics, and quantum
      computation. Herein, we demonstrate controllable magnetic modulation of alpha
      MnO2 nanowires, which displayed surface ferromagnetism or antiferromagnetism,
      depending on the exposed plane. First-principles density functional theory
      calculations confirm that both Mn- and O-terminated alpha-MnO2 (1 1 0) surfaces
      exhibit ferromagnetic ordering. The investigation of surface-controlled magnetic
      particles will lead to significant progress in our fundamental understanding of
      functional aspects of magnetism on the nanoscale, facilitating rational design of
      nanomagnets. Moreover, we approved that the facet engineering pave the way on
      designing semiconductors possessing unique properties for novel energy
      applications, owing to that the bandgap and the electronic transport of the
      semiconductor can be tailored via exposed surface modulations. 

PMID- 25758234
TI  - Paleontology and Darwin's Theory of Evolution: The Subversive Role of Statistics
      at the End of the 19th Century.
AB  - This paper examines the subversive role of statistics paleontology at the end of
      the 19th and the beginning of the 20th centuries. In particular, I will focus on
      German paleontology and its relationship with statistics. I argue that in
      paleontology, the quantitative method was questioned and strongly limited by the
      first decade of the 20th century because, as its opponents noted, when the fossil
      record is treated statistically, it was found to generate results openly in
      conflict with the Darwinian theory of evolution. Essentially, statistics
      questions the gradual mode of evolution and the role of natural selection. The
      main objections to statistics were addressed during the meetings at the
      Kaiserlich-Konigliche Geologische Reichsanstalt in Vienna in the 1880s. After
      having introduced the statistical treatment of the fossil record, I will use the
      works of Charles Leo Lesquereux (1806-1889), Joachim Barrande (1799-1833), and
      Henry Shaler Williams (1847-1918) to compare the objections raised in Vienna with
      how the statistical treatment of the data worked in practice. Furthermore, I will
      discuss the criticisms of Melchior Neumayr (1845-1890), one of the leading German
      opponents of statistical paleontology, to show why, and to what extent,
      statistics were questioned in Vienna. The final part of this paper considers what
      paleontologists can derive from a statistical notion of data: the necessity of
      opening a discussion about the completeness and nature of the paleontological
      data. The Vienna discussion about which method paleontologists should follow
      offers an interesting case study in order to understand the epistemic tensions
      within paleontology surrounding Darwin's theory as well as the variety of non
      Darwinian alternatives that emerged from the statistical treatment of the fossil
      record at the end of the 19th century. 

PMID- 25758233
TI  - Emotional and behavioural difficulties in children and adolescents with hearing
      impairment: a systematic review and meta-analysis.
AB  - The aim of this study is to estimate the extent to which children and adolescents
      with hearing impairment (HI) show higher rates of emotional and behavioural
      difficulties compared to normally hearing children. Studies of emotional and
      behavioural difficulties in children and adolescents were traced from
      computerized systematic searches supplemented, where appropriate, by studies
      referenced in previous narrative reviews. Effect sizes (Hedges' g) were
      calculated for all studies. Meta-analyses were conducted on the weighted effect
      sizes obtained for studies adopting the Strength and Difficulties Questionnaire
      (SDQ) and on the unweighted effect sizes for non-SDQ studies. 33 non-SDQ studies
      were identified in which emotional and behavioural difficulties in children with
      HI could be compared to normally hearing children. The unweighted average g for
      these studies was 0.36. The meta-analysis of the 12 SDQ studies gave estimated
      effect sizes of 0.23 (95% CI 0.07, 0.40), 0.34 (95% CI 0.19, 0.49) and -0.01 (95%
      CI -0.32, 0.13) for Parent, Teacher and Self-ratings of Total Difficulties,
      respectively. The SDQ sub-scale showing consistent differences across raters
      between groups with HI and those with normal hearing was Peer Problems. Children
      and adolescents with HI have scores on emotional and behavioural difficulties
      measures about a quarter to a third of a standard deviation higher than hearing
      children. Children and adolescents with HI are in need of support to help their
      social relationships particularly with their peers.

PMID- 25758235
TI  - Genotyping of hepatitis B and C virus Russian isolates for reference serum panel
      construction.
AB  - Approximately 2% and 5% of the world human population is estimated to be infected
      with HCV and HBV, respectively. Reference panels of HCV and HBV serum samples
      with defined genotypes and serotypes is necessary for monitoring of the
      specificity and sensitivity of diagnostic test kits. The aim of this study was to
      determine genotypes/serotypes of HBV and HCV circulating in Russia in order to
      construct a panel of reference sera containing these HCV genotypes and HBV
      serotypes. A total of 343 HBsAg-positive and 207 anti-HCV positive serum samples
      were collected from patients with HBV and HCV infection from different cities
      between years 2002 and 2010 in St. Petersburg, Krasnodar, Nizhny Novgorod,
      Novosibirsk, Barnaul, Gorno-Altaisk, and Khabarovsk. HBV DNA was found in 76.4%
      of HBsAg positive samples by PCR for the S gene and HCV RNA was found in 71.5,
      70.0, and 64.7% of anti-HCV positive samples in the 5'UTR, Core, and NS5B
      regions, respectively. The prevalence and proportion of HBV genotype/serotype
      associations were as follows: A/adw2, 2.1%; D/ayw2, 54.0%; D/ayw3, 43.1%; D/adw2,
      0.7%. A new combination of genotype D and adw2 serotype was discovered. The
      distribution of HCV genotypes was the following: 43.6%, b; 3.8%, 2a; and 52.6%,
      3a. Russian National reference panels of HBV and HCV lyophilized sera were
      developed to monitor specificity and sensitivity of approved kits and for the
      certification of newly developed assays.

PMID- 25758236
TI  - [Therapy of overactive bladder (OAB)].
AB  - Overactive bladder (OAB) is a symptom complex which is present in approximately
      17% of the European population. It is observed in the presence or absence of
      incontinence (wet or dry) and is associated with a high degree of psychological
      stress as well as high costs for the healthcare system. Myogenic, urothelial and
      neurogenic factors lead to frequently unknown changes of muscular, neural and
      connective tissue. For the definition, etiology and diagnostics of the disease
      the previous continuing medical education (CME) article "Diagnosis of overactive
      bladder (OAB)" should be consulted. In recent years some improvements have been
      made in OAB-related research, in terms of pathophysiological models and new
      pharmacological approaches with the development of new therapeutic agents.
      Besides classical substances, recently approved agents are increasingly being
      used for the therapy of OAB. Furthermore, non-pharmaceutical approaches and
      surgical techniques still play an important role in the therapy of OAB.

PMID- 25758237
TI  - [Intratumoral heterogeneity in renal cell carcinoma. Molecular basis and
      translational implications].
AB  - Advanced clear cell renal cell carcinoma is characterized by extensive
      intratumoral genomic heterogeneity and branched as well as convergent
      evolutionary traits with genomically different subclones evolving in parallel in
      the same tumor. Distinct driver mutations can be found in spatially separated
      subclones, which may hinder the development of novel targeted therapies. However,
      truncal mutations of the VHL tumor suppressor gene and chromosome 3p loss were
      ubiquitously detected and will hence continue to be a focus of future drug
      development. Nevertheless, genomic instability, enhanced tumor genome plasticity
      and intratumoral heterogeneity are likely to represent major challenges towards
      biomarker development and personalized patient care. 

PMID- 25758238
TI  - [Study and therapy of metastatic castration-resistant prostate cancer: A
      randomized, double blind, multicenter, parallel-group, phase III study to
      evaluate efficacy and safety of DCVAC/PCa versus placebo in men with metastatic
      castration resistant prostate cancer eligible for first line chemotherapy
      (VIABLE) - AUO study AP 78/13].

PMID- 25758239
TI  - Active vitamin D potentiates the anti-neoplastic effects of calcium in the colon:
      A cross talk through the calcium-sensing receptor.
AB  - Epidemiological studies suggest an inverse correlation between dietary calcium
      (Ca(2+)) and vitamin D intake and the risk of colorectal cancer (CRC). It has
      been shown in vitro that the active vitamin D metabolite, 1,25-dihydroxyvitamin
      D3 (1,25-D3) can upregulate expression of the calcium-sensing receptor (CaSR). In
      the colon, CaSR has been suggested to regulate proliferation of colonocytes.
      However, during tumorigenesis colonic CaSR expression is downregulated and we
      hypothesized that the loss of CaSR could influence the anti-tumorigenic effects
      of Ca(2+) and vitamin D. Our aim was to assess the impact of CaSR expression and
      function on the anti-neoplastic effects of 1,25-D3 in colon cancer cell lines. We
      demonstrated that in the healthy colon of mice, high vitamin D diet (2500 IU/kg
      diet) increased expression of differentiation and apoptosis markers, decreased
      expression of proliferation markers and significantly upregulated CaSR mRNA
      expression, compared with low vitamin D diet (100 IU/kg diet). To determine the
      role of CaSR in this process, we transfected Caco2-15 and HT29 CRC cells with
      wild type CaSR (CaSR-WT) or a dominant negative CaSR mutant (CaSR-DN) and treated
      them with 1,25-D3 alone, or in combination with CaSR activators (Ca(2+) and NPS R
      568). 1,25-D3 enhanced the anti-proliferative effects of Ca(2+) and induced
      differentiation and apoptosis only in cells with a functional CaSR, which were
      further enhanced in the presence of NPS R-568, a positive allosteric modulator of
      CaSR. The mutant CaSR inhibited the anti-tumorigenic effects of 1,25-D3
      suggesting that the anti-neoplastic effects of 1,25-D3 are, at least in part,
      mediated by the CaSR. Taken together, our data provides molecular evidence to
      support the epidemiological observation that both, vitamin D and calcium are
      needed for protection against malignant transformation of the colon and that
      their effect is modulated by the presence of a functional CaSR. This article is
      part of a Special Issue entitled '17th Vitamin D Workshop'.

PMID- 25758240
TI  - Problems With DSM-5 Somatic Symptom Disorder.

PMID- 25758241
TI  - Choosing the right drug to fit the patient when selecting oral anticoagulation
      for stroke prevention in atrial fibrillation.
AB  - Atrial fibrillation (AF) is the most common cardiac arrhythmia worldwide and is a
      growing health problem that is associated with a significantly increased risk of
      stroke and thromboembolism. Oral anticoagulant (OAC) therapy reduces the risk of
      stroke and all-cause mortality in patients with AF. OAC therapy is commonly given
      as a well-controlled vitamin K antagonist (VKA; e.g. warfarin) and can reduce the
      risk of stroke in AF patients by almost two-thirds. However, the widespread use
      of VKAs has been hampered by the unpredictable pharmacokinetic and
      pharmacodynamic properties of the drugs and justifiable concerns about the
      consequent risk of haemorrhage. The non-VKA OACs (NOACs) have revolutionized
      thromboprophylaxis in AF by providing therapeutic options with predictable
      pharmacodynamic and pharmacokinetic properties that are as efficacious as
      warfarin in the prevention of stroke and thromboembolism but are more convenient
      to use. In this review, we provide a patient-centred framework to assist
      clinicians in recommending the right OAC therapy to fit the individual patient
      with AF, including methods for stratifying the risk of stroke and haemorrhage and
      the chances of achieving tight control of VKA anticoagulation, and we discuss the
      properties of the NOACs that favour their use in particular patient cohorts.

PMID- 25758242
TI  - Rapid recombinant protein production from piggyBac transposon-mediated stable CHO
      cell pools.
AB  - Heterogeneous populations of stably transfected cells (cell pools) can serve for
      the rapid production of moderate amounts of recombinant proteins. Here, we
      propose the use of the piggyBac (PB) transposon system to improve the
      productivity and long-term stability of cell pools derived from Chinese hamster
      ovary (CHO) cells. PB is a naturally occurring genetic element that has been
      engineered to facilitate the integration of a transgene into the genome of the
      host cell. In this report PB-derived cell pools were generated after 10 days of
      selection with puromycin. The resulting cell pools had volumetric productivities
      that were 3-4 times higher than those achieved with cell pools generated by
      conventional plasmid transfection even though the number of integrated transgene
      copies per cell was similar in the two populations. In 14-day batch cultures,
      protein levels up to 600 and 800 mg/L were obtained for an Fc-fusion protein and
      a monoclonal antibody, respectively, at volumetric scales up to 1L. In general,
      the volumetric protein yield from cell pools remained constant for up to 3 months
      in the absence of selection. In conclusion, transfection of CHO cells with the PB
      transposon system is a simple, efficient, and reproducible approach to the
      generation of cell pools for the rapid production of recombinant proteins.

PMID- 25758243
TI  - Glomerulonephritis-Induced Changes in Urinary and Kidney MicroRNA Profiles in
      Rats.
AB  - MicroRNAs (miRNAs) regulate gene expression post-transcriptionally and thus are
      involved in various physiological and pathological states. Due to their stability
      in biofluids miRNAs have also been proposed as biomarkers (BMs) for tissue
      injury. We investigated the usefulness of urinary miRNAs for detection of site
      specific renal damage in an antiglomerular basement membrane glomerulonephritis
      (GN) model in rats by comparing GN-induced urinary miRNAs profiles to traditional
      and newer protein BMs, and to proximal tubular injury-induced urinary miRNA
      profiles observed previously after cisplatin (Cp) treatment. Male Wistar Kyoto
      and Sprague Dawley rats were dosed once with 1, 2.5, and 5 ml/kg nephrotoxic
      serum (NTS) or 1.5 and 5 ml/kg NTS, respectively. GN and tubular damage were
      observed histopathologically in all treated rats after 14 days. Although serum
      creatinine and BUN were not changed, several protein BMs and 74 urinary miRNAs
      were found to be increased 8 and 14 days after NTS administration. Of these 74
      miRNAs, 5 were identified as increased after NTS but not after Cp treatment.
      Using in situ hybridization two of them, miR-10 b and -100, were found to be
      localized in distal segments of the nephron, potentially reflecting the tubular
      injury in those regions. Furthermore, evaluation of both miRNA and mRNA
      expression in the kidney revealed possible miRNA-mRNA interactions mostly
      associated with fibrotic and transforming growth factor beta signaling. In
      conclusion, our investigations support the potential of urinary miRNAs as
      specific BMs for kidney injury, and suggest a role of miRNAs in pathological
      processes during GN in the kidney.

PMID- 25758244
TI  - Age-related decrease in theta and gamma coherence across dorsal ca1 pyramidale
      and radiatum layers.
AB  - In both humans and rodents, aging is linked to impairments in hippocampus
      dependent learning. Given such deficits, one would expect corresponding changes
      in hippocampal local field potentials, which represent the integration of
      multiple inputs onto a given dendritic field within the hippocampus. The current
      experiment examined coherence of theta and gamma in young and aged rats at sub
      millimeter and millimeter distant locations both within and across layers in CA1
      of the dorsal hippocampus. The degree to which different dendritic layers show
      coherent oscillations indicates the uniformity of the inputs and local circuitry,
      and may form an important element for processing information. Aged rats had lower
      coherence in all frequency ranges; this was most marked within a layer as the
      distance between electrodes increased. Notably, unlike younger rats, in the aged
      rats coherence was not affected by running on the maze. Furthermore, despite the
      previously reported effects of cholinergic activation on theta frequency and
      power, there was no effect of the cholinomimetic physostigmine on coherence.
      These data indicate an age related fragmentation in hippocampal processing that
      may underlie some of the observed learning and memory deficits.

PMID- 25758245
TI  - An organizational seat at the table: advocacy based on science and education.

PMID- 25758246
TI  - Can GPs do more to help patients with facial disfigurement?

PMID- 25758249
TI  - Circadian systems biology in Metazoa.
AB  - Systems biology, which can be defined as integrative biology, comprises
      multistage processes that can be used to understand components of complex
      biological systems of living organisms and provides hierarchical information to
      decoding life. Using systems biology approaches such as genomics, transcriptomics
      and proteomics, it is now possible to delineate more complicated interactions
      between circadian control systems and diseases. The circadian rhythm is a
      multiscale phenomenon existing within the body that influences numerous
      physiological activities such as changes in gene expression, protein turnover,
      metabolism and human behavior. In this review, we describe the relationships
      between the circadian control system and its related genes or proteins, and
      circadian rhythm disorders in systems biology studies. To maintain and modulate
      circadian oscillation, cells possess elaborative feedback loops composed of
      circadian core proteins that regulate the expression of other genes through their
      transcriptional activities. The disruption of these rhythms has been reported to
      be associated with diseases such as arrhythmia, obesity, insulin resistance,
      carcinogenesis and disruptions in natural oscillations in the control of cell
      growth. This review demonstrates that lifestyle is considered as a fundamental
      factor that modifies circadian rhythm, and the development of dysfunctions and
      diseases could be regulated by an underlying expression network with multiple
      circadian-associated signals. 

PMID- 25758250
TI  - Dietary intake patterns and diet quality in a nationally representative sample of
      women with and without severe headache or migraine.
AB  - OBJECTIVE/BACKGROUND: The role of diet in migraine is not well understood. We
      sought to characterize usual dietary intake patterns and diet quality in a
      nationally representative sample of women with and without severe headache or
      migraine. We also examined whether the relationship between migraine and diet
      differs by weight status. METHODS: In this analysis, women with migraine or
      severe headache status was determined by questionnaire for 3069 women, ages 20-50
      years, who participated in the National Health and Nutrition Examination Study,
      1999-2004. Women who experienced severe headaches or migraines were classified as
      migraine for the purposes of this analysis. Dietary intake patterns (micro- and
      macronutrient intake and eating frequency) and diet quality, measured by the
      Healthy Eating Index, 2005, were determined using one 24-hour dietary recall.
      RESULTS: Dietary intake patterns did not significantly differ between women with
      and without migraine. Normal weight women with migraine had significantly lower
      diet quality (Healthy Eating Index, 2005 total scores) than women without
      migraine (52.5 +/- 0.9 vs. 45.9 +/- 1.0; P < .0001). CONCLUSIONS: Whereas
      findings suggest no differences in dietary intake patterns among women with and
      without migraine, dietary quality differs by migraine status in normal weight
      women. Prospective analyses are needed to establish how diet relates to migraine
      onset, characteristics, and clinical features in individuals of varying weight
      status.

PMID- 25758251
TI  - Antiviral antibody profiling by high-density protein arrays.
AB  - Viral infections elicit antiviral antibodies and have been associated with
      various chronic diseases. Detection of these antibodies can facilitate diagnosis,
      treatment of infection, and understanding of the mechanisms of virus-associated
      diseases. In this work, we assayed antiviral antibodies using a novel high
      density nucleic acid programmable protein array (HD-NAPPA) platform. Individual
      viral proteins were expressed in situ directly from plasmids encoding proteins in
      an array of microscopic reaction chambers. Quality of protein display and serum
      response was assured by comparing intra- and inter-array correlation within or
      between printing batches with average correlation coefficients of 0.91 and 0.96,
      respectively. HD-NAPPA showed higher signal-to-background ratio compared with
      standard NAPPA on planar glass slides and ELISA. Antibody responses to 761
      antigens from 25 different viruses were profiled among patients with juvenile
      idiopathic arthritis and type 1 diabetes. Common and unique antibody reactivity
      patterns were detected between patients and healthy controls. We believe HD-viral
      NAPPA will enable the study of host-pathogen interactions at unprecedented
      dimensions and elucidate the role of pathogen infections in disease development. 

PMID- 25758252
TI  - Prevalence and risk factors of low back pain among undergraduate students of a
      sports and physical education institute in Tunisia.
AB  - Introduction : For obvious reasons, athletes are at greater risk of sustaining a
      lumber (lower) spine injury due to physical activity. To our knowledge, no
      previous studies have examined the prevalence of low back pain (LBP) in a
      Tunisian sports and physical education institute. Aim : To assess the prevalence
      of LBP in different sports among students studying in a sports and physical
      education institute in Tunisia, to determine the causes of the injuries, and to
      propose solutions. Methods : A total of 3,379 boys and 2,579 girls were studied.
      A retrospective cross-sectional survey was conducted on a group of students aged
      18.5-24.5 years at the Higher Institute of Sport and Physical Education of Sfax
      to estimate the prevalence of LBP and its relation to the type of sports. Data on
      age, weight, height, smoking, and the sport in which the student was injured in
      the low back were collected from the institute health service records from 2005
      until 2013. Results : LBP was reported by 879 of the 5,958 study participants
      (14.8%). The prevalence of LBP was significantly higher (p<0.001) in females
      (17.6%) than in males (12.5%). LBP prevalence did not differ by body mass index
      or smoking habit (p>0.05). The sports associated with the higher rates of LBP
      were gymnastics, judo, handball, and volleyball, followed by basketball and
      athletics. Conclusion : LBP is frequent among undergraduate students of a sports
      and physical education institute in Tunisia. It is strongly associated with
      fatigue after the long periods of training in different sports. Gymnastics, judo,
      handball, and volleyball were identified as high-risk sports for causing LBP. 

PMID- 25758254
TI  - Epigenetic-related therapeutic challenges in cardiovascular disease.
AB  - Progress in human genetic and genomic research has led to the identification of
      genetic variants associated with specific cardiovascular diseases (CVDs), but the
      pathogenic mechanisms remain unclear. Recent studies have analyzed the
      involvement of epigenetic mechanisms such as DNA methylation and histone
      modifications in the development and progression of CVD. Preliminary work has
      investigated the correlations between DNA methylation, histone modifications, and
      RNA-based mechanisms with CVDs including atherosclerosis, heart failure (HF),
      myocardial infarction (MI), and cardiac hypertrophy. Remarkably, both in utero
      programming and postnatal hypercholesterolemia may affect the epigenetic
      signature in the human cardiovascular system, thereby providing novel early
      epigenetic-related pharmacological insights. Interestingly, some dietary
      compounds, including polyphenols, cocoa, and folic acid, can modulate DNA
      methylation status, whereas statins may promote epigenetic-based control in CVD
      prevention through histone modifications. We review recent findings on the
      epigenetic control of cardiovascular system and new challenges for therapeutic
      strategies in CVDs. 

PMID- 25758253
TI  - p53 Family Members Regulate Phenotypic Response to Aurora Kinase A Inhibition in
      Triple-Negative Breast Cancer.
AB  - Triple-negative breast cancer (TNBC) is an aggressive disease with a poor
      prognosis. Advances in the treatment of TNBC have been hampered by the lack of
      novel effective targeted therapies. The primary goal of this study was to
      evaluate the efficacy of targeting Aurora kinase A (AurA), a key regulator of
      mitosis, in TNBC models. A secondary objective was to determine the role of the
      p53 family of transcriptional regulators, commonly mutated in TNBC, in
      determining the phenotypic response to the AurA inhibitor alisertib (MLN8237).
      Alisertib exhibited potent antiproliferative and proapoptotic activity in a
      subset of TNBC models. The induction of apoptosis in response to alisertib
      exposure was dependent on p53 and p73 activity. In the absence of functional p53
      or p73, there was a shift in the phenotypic response following alisertib exposure
      from apoptosis to cellular senescence. In addition, senescence was observed in
      patient-derived tumor xenografts with acquired resistance to alisertib treatment.
      AurA inhibitors are a promising class of novel therapeutics in TNBC. The role of
      p53 and p73 in mediating the phenotypic response to antimitotic agents in TNBC
      may be harnessed to develop an effective biomarker selection strategy in this
      difficult to target disease.

PMID- 25758255
TI  - The addition of beta-hydroxy-beta-methylbutyrate and isomaltulose to whey protein
      improves recovery from highly demanding resistance exercise.
AB  - OBJECTIVE: This study evaluated whether a combination of whey protein (WP),
      calcium beta-hydroxy-beta-methylbutyrate (HMB), and carbohydrate exert additive
      effects on recovery from highly demanding resistance exercise. METHODS: Thirteen
      resistance-trained men (age: 22.6 +/- 3.9 years; height: 175.3 +/- 12.2 cm;
      weight: 86.2 +/- 9.8 kg) completed a double-blinded, counterbalanced, within
      group study. Subjects ingested EAS Recovery Protein (RP; EAS Sports
      Nutrition/Abbott Laboratories, Columbus, OH) or WP twice daily for 2 weeks prior
      to, during, and for 2 days following 3 consecutive days of intense resistance
      exercise. The workout sequence included heavy resistance exercise (day 1) and
      metabolic resistance exercise (days 2 and 3). The subjects performed no physical
      activity during day 4 (+24 hours) and day 5 (+48 hours), where recovery testing
      was performed. Before, during, and following the 3 workouts, treatment outcomes
      were evaluated using blood-based muscle damage markers and hormones, perceptual
      measures of muscle soreness, and countermovement jump performance. RESULTS:
      Creatine kinase was lower for the RP treatment on day 2 (RP: 166.9 +/- 56.4 vs
      WP: 307.1 +/- 125.2 IU . L(-1), p <= 0.05), day 4 (RP: 232.5 +/- 67.4 vs WP:
      432.6 +/- 223.3 IU . L(-1), p <= 0.05), and day 5 (RP: 176.1 +/- 38.7 vs 264.5 +/
      120.9 IU . L(-1), p <= 0.05). Interleukin-6 was lower for the RP treatment on
      day 4 (RP: 1.2 +/- 0.2 vs WP: 1.6 +/- 0.6 pg . ml(-1), p <= 0.05) and day 5 (RP:
      1.1 +/- 0.2 vs WP: 1.6 +/- 0.4 pg . ml(-1), p <= 0.05). Muscle soreness was lower
      for RP treatment on day 4 (RP: 2.0 +/- 0.7 vs WP: 2.8 +/- 1.1 cm, p <= 0.05).
      Vertical jump power was higher for the RP treatment on day 4 (RP: 5983.2 +/- 624
      vs WP 5303.9 +/- 641.7 W, p <= 0.05) and day 5 (RP: 5792.5 +/- 595.4 vs WP:
      5200.4 +/- 501 W, p <= 0.05). CONCLUSIONS: Our findings suggest that during times
      of intense conditioning, the recovery benefits of WP are enhanced with the
      addition of HMB and a slow-release carbohydrate. We observed reductions in
      markers of muscle damage and improved athletic performance.

PMID- 25758256
TI  - Use of an Electromagnetic Device Compared With Chest X-ray to Confirm Nasogastric
      Feeding Tube Position in Critical Care.
AB  - BACKGROUND: Insertion of nasogastric feeding tubes (NGTs) is common in critical
      care. However, misplacement is frequent and can carry a significant morbidity.
      Current methods to confirm position of NGTs are not reliable in this setting. We
      retrospectively compared the position of NGTs using an electromagnetically guided
      nasogastric tube (e-NGT) with that demonstrated by chest x-ray (CXR), the
      proportion of lung placements avoided, and the time taken to establish enteral
      feeding. METHODS: This was a retrospective, observational study undertaken in a
      tertiary referral, adult intensive care unit between February 2006 and November
      2013. Patients were included if they had a radiologically confirmed NGT. All CXRs
      were independently reviewed by an intensivist to determine position, and a subset
      of patients had their e-NGT image independently reviewed for quality control.
      Statistical analysis was in the form of sensitivity and specificity and
      descriptive where indicated. RESULTS: In total, 121 NGT placements in 113
      patients were analyzed. We found a sensitivity of 98% (95% confidence interval
      [CI], 93.9%-99.7%) and a specificity of 100% (95% CI, 48.0%-100.0%) when using
      the e-NGT compared with CXR. In the subset of 51 independently reviewed e-NGT
      images, 9 lung placements were avoided. The mean (SD) time from e-NGT placement
      to CXR was 185 (264.4) minutes and to feeding was 404 (77.8) minutes. CONCLUSION:
      When placed by a dedicated team, e-NGT allowed immediate detection of tube
      misplacement. As such, if used as the sole method for determining NGT position, e
      NGTs minimize feeding delay and the need for multiple CXRs with subsequent cost
      savings.

PMID- 25758257
TI  - Role of zinc-finger anti-viral protein in host defense against Sindbis virus.
AB  - Accumulating evidence indicates that type I interferon (IFN) mediates the host
      protective response to RNA viruses. However, the anti-viral effector molecules
      involved in this response have not been fully identified. Here, we show that zinc
      finger anti-viral protein (ZAP), an IFN-inducible gene, plays a critical role in
      the elimination of Sindbis virus (SINV) in vitro and in vivo. The loss of ZAP
      greatly enhances the replication of SINV but does not inhibit type I IFN
      production in primary mouse embryonic fibroblasts (MEFs). ZAP binds and
      destabilizes SINV RNA, thereby suppressing the replication of SINV. Type I IFN
      fails to suppress SINV replication in ZAP-deficient MEFs, whereas the ectopic
      expression of ZAP is sufficient to suppress the replication of SINV in MEFs
      lacking the expression of type I IFN and the IFN-inducible genes. ZAP-deficient
      mice are highly susceptible to SINV infection, although they produce sufficient
      amounts of type I IFN. Therefore, ZAP is an RNA-sensing anti-viral effector
      molecule that mediates the type-I-IFN-dependent host defense against SINV. 

PMID- 25758258
TI  - A pilot longitudinal study of the use of waxy maize heat modified starch in the
      treatment of adults with glycogen storage disease type I: a randomized double
      blind cross-over study.
AB  - BACKGROUND: Uncooked corn-starch (UCCS) has been the mainstay of therapy for the
      hepatic glycogen storage diseases (GSD) but is not always effective. A new starch
      (WMHMS) has demonstrated a more favourable short-term metabolic profile.
      OBJECTIVE: To determine efficacy and safety of a new uncooked starch (WMHMS)
      compared to UCCS over 16 weeks treatment with each. METHOD: A double-blind cross
      over study of 10 adults (aged 16 - 38 years, six male) with GSD Ia and Ib. After
      an individualised fast, subjects were randomised to take a 50 g starch-load of
      either WMHMS or UCCS. Starch-loads terminated when blood glucose was < 3.0 mmol/L
      or the subject felt subjectively hypoglycaemic. Anonymous biochemical profiles
      were assessed by 2 investigators and a starch administration schedule
      recommended. Each starch was delivered in coded sachets and intake was monitored
      for the following 16 weeks. After a washout period, the protocol was repeated
      with the alternative product. RESULTS: 4 subjects failed to establish therapy on
      the cross-over limb. Data from 7 paired starch load showed: longer median fasting
      duration with WMHMS (7.5 versus 5 hours; p = 0.023), slower decrease in the
      glucose curve (0.357 versus 0.632 mmol/hr p = 0.028) and less area under insulin
      curves for the first 4 hours (p = 0.03). Two of six subjects took 50% or less
      WMHMS compared to UCCS and one took more. Plasma triglycerides, cholesterol and
      uric acid were unchanged after each study phase. CONCLUSION: WMHMS leads to
      significant reduction in insulin release and reduced starch use in some GSD
      patients.

PMID- 25758259
TI  - Piezotronic-effect enhanced drug metabolism and sensing on a single ZnO nanowire
      surface with the presence of human cytochrome P450.
AB  - Cytochromes P450 (CYPs) enzymes are involved in catalyzing the metabolism of
      various endogenous and exogenous compounds. A rapid analysis of drug metabolism
      reactions by CYPs is required because they can metabolize 95% of current drugs in
      drug development and effective therapies. Here, we describe a study of
      piezotronic-effect enhanced drug metabolism and sensing by utilizing a single ZnO
      nanowire (ZnO NW) device. Owing to the unique hydrophobic feature of a ZnO NW
      that provides a desirable "microenvironment" for the immobilization of
      biomolecules, our device can effectively stimulate the tolbutamide metabolism by
      decorating a ZnO NW with cytochrome P4502C9/CYPs reductase (CYP2C9/CPR)
      microsomes. By applying an external compressive strain to the ZnO nanowire, the
      piezotronic effect, which plays a primary role in tuning the transport behavior
      of a ZnO NW utilizing the created piezoelectric polarization charges at the local
      interface, can effectively enhance the performance of the device. A theoretical
      model is proposed using an energy band diagram to explain the experimental data.
      This study provides a potential approach to study drug metabolism and trace drug
      detection based on the piezotronic effect. 

PMID- 25758260
TI  - Optimizing the duration of dual antiplatelet therapy after implantation of drug
      eluting coronary stents.

PMID- 25758261
TI  - Clinical impact of dual antiplatelet therapy use in patients following everolimus
      eluting stent implantation: insights from the SEEDS study.
AB  - BACKGROUND: Studies have suggested that use of prolonged dual antiplatelet
      therapy (DAPT) following new generation drug-eluting stent implantation may
      increase costs and potential bleeding events. This study aimed to investigate the
      association of DAPT status with clinical safety in patients undergoing everolimus
      eluting stent (EES) implantation in the SEEDS study (A Registry to Evaluate
      Safety and Effectiveness of Everolimus Drug-eluting Stent for Coronary
      Revascularization) at 2-year follow-up. METHODS: The SEEDS study is a
      prospective, multicenter study, where patients (n = 1900) with small vessel, long
      lesion, or multi-vessel diseases underwent EES implantation. Detailed DAPT status
      was collected at baseline, 6-month, 1- and 2-year. DAPT interruption was defined
      as any interruption of aspirin and/or clopidogrel more than 14 days. The net
      adverse clinical events (NACE, a composite endpoint of all-cause death, all
      myocardial infarction (MI), stroke, definite/probable stent thrombosis (ST), and
      major bleeding (Bleeding Academic Research Consortium II-V)) were investigated
      according to the DAPT status at 2-year follow-up. RESULTS: DAPT was used in 97.8%
      of patients at 6 months, 69.5% at 12 months and 35.4% at 2 years. It was observed
      that the incidence of NACE was low (8.1%) at 2 years follow-up, especially its
      components of all-cause death (0.9%), stroke (1.1%), and definite/probable ST
      (0.7%). DAPT was not an independent predictor of composite endpoint of all-cause
      death/MI/stroke (hazard ratio [HR]: 0.693, 95% confidence interval [CI]: 0.096
      4.980, P = 0.715) and NACE (HR: 1.041, 95% CI: 0.145-7.454, P = 0.968). Of 73
      patients who had DAPT interruption, no patient had ST at 12-month, and only 1
      patient experienced ST between 1- and 2-year (1.4%). There was a high frequency
      of major bleeding events (53/65, 82.5%) occurred in patients receiving DAPT
      treatment. CONCLUSIONS: Prolonged DAPT use was not associated with improved
      clinical safety. The study emphasized that duration of DAPT needs to be shortened
      in Chinese patients following EES implantation (ClinicalTrials.gov identifier:
      NCT 01157455).

PMID- 25758263
TI  - Clinical utility of the ratio between circulating fibrinogen and fibrin (ogen)
      degradation products for evaluating coronary artery disease in type 2 diabetic
      patients.
AB  - BACKGROUND: We investigated whether and to what extent the ratio between
      circulating fibrinogen (Fg) and its degradation products (FDP) reflects the
      severity of coronary artery disease (CAD) in type 2 diabetic patients. METHODS:
      Plasma levels of Fg and FDP were determined, and Fg/FDP ratio was calculated in
      344 consecutive patients with type 2 diabetes and chest pain on exertion
      undergoing coronary angiography. The severity of CAD was evaluated by the number
      of significant CAD (>50% luminal diameter narrowing) and Gensini score. RESULTS:
      Plasma Fg was higher, but Fg/FDP ratio was lower in patients with significant CAD
      (n = 255) compared with those without (n = 89), due to a disproportionate
      increase in FDP. Fg and FDP correlated positively, while Fg/FDP ratio negatively,
      with the number of diseased coronary arteries and the tertile of Gensini score
      (all P values for trend < 0.01). After adjusting for age, sex, risk factors for
      CAD, lipid profiles, glycosylated hemoglobin A1c, creatinine, leukocyte count,
      and high-sensitivity C-reactive protein, Fg/FDP ratio remained an independent
      determinant for multivessel coronary disease (MVD) (odds ratio [OR], 0.869; 95%
      confidence interval [CI], 0.788-0.958, P = 0.005) and high tertile of Gensini
      score (OR, 0.797, 95% CI, 0.682-0.930, P = 0.004). The area under the curve of
      Fg/FDP ratio was larger than that of Fg for predicting the presence of MVD (0.647
      vs. 0.563, P = 0.048) and Gensini score >= 30 (0.656 vs. 0.538, P = 0.026).
      CONCLUSIONS: Elevated plasma Fg and FDP level and reduced Fg/FDP ratio are
      associated with presence of CAD, and Fg/FDP ratio is superior to Fg in reflecting
      severe coronary atherosclerosis for patients with type 2 diabetes.

PMID- 25758262
TI  - Comparison of the efficacy of drug-eluting stents versus bare-metal stents for
      the treatment of left main coronary artery disease.
AB  - BACKGROUND: Recent studies reported that percutaneous coronary intervention with
      stent implantation was safe and feasible for the treatment of left main coronary
      artery (LMCA) disease in select patients. However, it is unclear whether drug
      eluting stents (DESs) have better outcomes in patients with LMCA disease compared
      with bare-metal stent (BMS) during long-term follow-up in Chinese populations.
      METHODS: From a perspective multicenter registry, 1136 consecutive patients, who
      underwent BMS or DES implantation for unprotected LMCA stenosis, were divided
      into two groups: 1007 underwent DES implantation, and 129 underwent BMS
      implantation. The primary outcome was the rate of major adverse cardiac events
      (MACEs), including cardiovascular (CV) death, myocardial infarction (MI), and
      target lesion revascularization (TLR) at 5 years postimplantation. RESULTS:
      Patients in the DES group were older and more likely to have hyperlipidemia and
      bifurcation lesions. They had smaller vessels and longer lesions than patients in
      the BMS group. In the adjusted cohort of patients, the DES group had
      significantly lower 5 years rates of MACE (19.4% vs. 31.8%, P = 0.022), CV death
      (7.0% vs. 14.7%, P = 0.045), and MI (5.4% vs. 12.4%, P = 0.049) than the BMS
      group. There were no significant differences in the rate of TLR (10.9% vs. 17.8%,
      P = 0.110) and stent thrombosis (4.7% vs. 3.9%, P = 0.758). The rates of MACE
      (80.6% vs. 68.2%, P = 0.023), CV death (93.0% vs. 85.3%, P = 0.045), TLR (84.5%
      vs. 72.1%, P = 0.014), and MI (89.9% vs. 80.6%, P = 0.029) free survival were
      significantly higher in the DES group than in the BMS group. When the propensity
      score was included as a covariate in the Cox model, the adjusted hazard ratios
      for the risk of CV death and MI were 0.41 (95% confidence interval [CI]: 0.21
      0.63, P = 0.029) and 0.29 (95% CI: 0.08-0.92, P = 0.037), respectively.
      CONCLUSIONS: DES implantation was associated with more favorable clinical
      outcomes than BMS implantation for the treatment of LMCA disease even though
      there was no significant difference in the rate of TLR between the two groups.

PMID- 25758264
TI  - Effect of final kissing balloon dilatation after one-stent technique at left-main
      bifurcation: a single center data.
AB  - BACKGROUND: Whether final kissing balloon (FKB) dilatation after one-stent
      implantation at left-main (LM) bifurcation site remains unclear. Therefore, this
      large sample and long-term follow-up study comparatively assessed the impact of
      FKB in patients with unprotected LM disease treated with one-stent strategy.
      METHODS: Total 1528 consecutive patients underwent LM percutaneous coronary
      intervention in one center from January 2004 to December 2010 were enrolled;
      among them, 790 patients treated with one drug-eluting stent crossover LM to left
      anterior descending (LAD) with FKB (n = 230) or no FKB (n = 560) were
      comparatively analyzed. Primary outcome was the rate of major adverse
      cardiovascular events, defined as a composite of death, myocardial infarction
      (MI) and target vessel revascularization (TVR). RESULTS: Overall, The prevalence
      of true bifurcation lesions, which included Medina classification (1,1,1),
      (1,0,1), or (0,1,1), was similar between-groups (non-FKB: 37.0% vs. FKB: 39.6%, P
      = 0.49). At mean 4 years follow-up, rates of major adverse cardiovascular events
      (non-FKB: 10.0% vs. FKB: 7.8%, P = 0.33), death, MI and TVR were not
      significantly different between-groups. In multivariate propensity-matched
      regression analysis, FKB was not an independent predictor of adverse outcomes.
      CONCLUSIONS: For patients treated with one-stent crossover LM to LAD, clinical
      outcomes appear similar between FKB and non-FKB strategy.

PMID- 25758265
TI  - Transcatheter aortic valve implantation assisted with microcatheter: a new method
      to avoid coronary artery obstruction.
AB  - BACKGROUND: Lack of fluoroscopic landmarks can make valve deployment more
      difficult in patients with absent aortic valve (AV) calcification. The goal of
      this article was to evaluate the feasibility and effectiveness of transcatheter
      implantation of a valved stent into the AV position of a goat, assisted with a
      microcatheter which provides accurate positioning of coronary artery ostia to
      help valved stent deployment. METHODS: The subjects were 10 healthy goats in this
      study. A microcatheter was introduced into the distal site of right coronary
      artery (RCA) through femoral artery sheath. A minimal thoracic surgery approach
      was used to access the apex of the heart. The apex of the left ventricle was
      punctured; a delivery catheter equipped with the valved stent was introduced over
      a stiff guidewire into the aorta arch. We could accurately locate the RCA ostia
      through the microcatheter placed in the RCA under fluoroscopy. After correct
      valve position was confirmed, the valved stent was implanted after rapid
      inflation of the balloon. The immediate outcome of the function of the valved
      stents was evaluated after implantation. RESULTS: All ten devices were
      successfully implanted into the AV position of the goats. Immediate observation
      after the procedure showed that the valved stents were in the desired position
      after implantation by angiography, echocardiogram. No obstruction of coronary
      artery ostia occurred, and no moderate to severe aortic regurgitation was
      observed. CONCLUSIONS: When the procedure of transcatheter implantation of a
      balloon-expandable valved stent into the AV position of goats is assisted with
      microcatheter positioning coronary artery ostia, the success rate of operation
      can be increased in those with noncalcified AV.

PMID- 25758266
TI  - Effect of transcatheter embolization by autologous fat particles in the treatment
      of coronary artery perforation during percutaneous coronary intervention.
AB  - BACKGROUND: Coronary artery perforation (CAP) is a rare but severe complication
      of percutaneous coronary intervention (PCI). The aim of our study was to evaluate
      the effect and safety of transcatheter embolization by autologous fat particles
      in the treatment of CAP. METHODS: Once the CAP was confirmed, a little autologous
      subcutaneous fatty tissue was obtained from the groin of the patient and then was
      made into 1 mm * 1 mm fat particles. The perforated vessel was embolized by fat
      particles via a micro-catheter. There were eight patients undergoing
      transcatheter embolization by autologous fat particles in the treatment of CAP
      during PCI in Peking University Third Hospital from February 2009 to June 2014,
      and the clinical data of these patients were collected and analyzed
      retrospectively. RESULTS: The lesion morphology of the patients was classified
      based on the American College of Cardiology/American Heart Association Task Force
      classification, there were one patient with Class B2 lesion and seven patients
      with Class C lesions (there were five patients with chronic total occlusion
      lesions). According to the Ellis classification of CAP, there were six patients
      with Class II perforations and two patients with Class III perforations. The
      causes of perforation included that seven patients induced by guide wire and one
      patient by balloon predilation. Three patients had pericardial effusion. All of
      the eight patients with CAP underwent transcatheter embolization by autologous
      fat particles. Coronary angiography confirmed that all of them were embolized
      successfully. There was no severe complication after the procedure. The coronary
      angiography of one patient at 1 week and another patient at 2 years after the
      embolization showed that the embolized arteries had recanalized. The median
      follow-up time was 20.3 months (8.8-50.2 months), the event-free survival rate
      was 100%. CONCLUSIONS: Transcatheter embolization by autologous fat particles was
      an effective, safe, cheap, and easy way to treat the perforation of small vessels
      during PCI.

PMID- 25758267
TI  - Decrease of glomerular filtration rate may be attributed to the microcirculation
      damage in renal artery stenosis.
AB  - BACKGROUND: The decrease of glomerular filtration rate has been theoretically
      supposed to be the result of low perfusion in renal artery stenosis (RAS). But
      the gap between artery stenosis and the glomerular filtration ability is still
      unclear. METHODS: Patients with selective renal artery angiogram were divided by
      the degree of renal artery narrowing, level of estimated glomerular filtration
      rate (eGFR), respectively. The different levels of eGFR, renal microcirculation
      markers, and RAS severity were compared with each other, to determine the
      relationships among them. RESULTS: A total of 215 consecutive patients were
      enrolled in the prospective cohort study. Concentrations of microcirculation
      markers had no significant difference between RAS group (RAS >= 50%) and no RAS
      group (RAS < 50%) or did not change correspondingly to RAS severity. The value of
      eGFR in RAS group was lower than that in the no RAS group, but it did not decline
      parallel to the progressive severity of RAS. The microcirculation markers
      presented integral difference if grouped by different eGFR level with negative
      tendency, especially that plasma cystatin C (cysC) and urinary microalbumin to
      creatinine ratio (mACR) increased with the deterioration of eGFR, with strong (r
      = -0.713, P < 0.001) and moderate (r = -0.580, P < 0.001) correlations. In the
      subgroup analysis of severe RAS (RAS >= 80%), the levels of plasma cysC and
      urinary mACR demonstrated stronger negative associations with eGFR, (r = -0.827,
      P < 0.001) and (r = -0.672, P < 0.001) correlations, respectively. CONCLUSIONS:
      Severity of RAS could not accurately predict the value of eGFR, whereas
      microcirculation impairment may substantially contribute to the glomerular
      filtration loss in patients with RAS.

PMID- 25758268
TI  - Plasma alpha1-antitrypsin: a neglected predictor of angiographic severity in
      patients with stable angina pectoris.
AB  - BACKGROUND: As an acute phase protein, alpha1-antitrypsin (AAT) has been
      extensively studied in acute coronary syndrome, but it is unclear whether a
      relationship exists between AAT and stable angina pectoris (SAP). The purpose of
      the present study was to investigate the association between AAT plasma levels
      and SAP. METHODS: Overall, 103 SAP patients diagnosed by coronary angiography and
      clinical manifestations and 118 control subjects matched for age and gender were
      enrolled in this case-control study. Plasma levels of AAT, high-sensitivity C
      reactive protein (hsCRP), lipid profiles and other clinical parameters were
      assayed for all participants. The severity of coronary lesions was evaluated
      based on the Gensini score (GS) assessed by coronary angiography. RESULTS:
      Positively correlated with the GS (r = 0.564, P < 0.001), the plasma AAT level in
      the SAP group was significantly higher than that in the control group (142.08 +/-
      19.61 mg/dl vs. 125.50 +/- 19.67 mg/dl, P < 0.001). The plasma AAT level was an
      independent predictor for both SAP (odds ratio [OR] = 1.037, 95% confidence
      interval [CI]: 1.020-1.054, P < 0.001) and a high GS (OR = 1.087, 95% CI: 1.051
      1.124, P < 0.001) in a multivariate logistic regression model. In the receiver
      operating characteristic curve analysis, plasma AAT level was found to have a
      larger area under the curve (AUC) for predicting a high GS (AUC = 0.858, 95% CI:
      0.788-0.929, P < 0.001) than that of hsCRP (AUC = 0.665, 95% CI: 0.557-0.773, P =
      0.006; Z = 2.9363, P < 0.001), with an optimal cut-off value of 137.85 mg/dl
      (sensitivity: 94.3%, specificity: 68.2%). CONCLUSIONS: Plasma AAT levels
      correlate with both the presence and severity of coronary stenosis in patients
      with SAP, suggesting that it could be a potential predictive marker of severe
      stenosis in SAP patients.

PMID- 25758269
TI  - A comparison of the transradial and transfemoral approaches for the angiography
      and intervention in patients with a history of coronary artery bypass surgery: in
      hospital and 1-year follow-up results.
AB  - BACKGROUND: Percutaneous coronary intervention (PCI) through transradial approach
      (TRA) has shown to be safe and effective as transfemoral approach (TFA) among
      unselected patients. However, very few studies have compared the outcomes between
      TRA and TFA specifically in patients with a history of coronary artery bypass
      grafting surgery (CABG). METHODS: A total of 404 post-CABG patients who had
      undergone angiography or PCI were included in the study. The primary endpoint was
      defined as angiographic success and procedure success. The secondary endpoint was
      defined as in-hospital net adverse clinical events (NACEs), which included all
      cause of death, myocardial infarction (MI), stroke, repeat revascularization, and
      major bleeding. Patients were followed-up for 1-year. Major adverse
      cardiovascular events (MACEs), which included death, MI, and repeat
      revascularization, at 1-year follow-up were also compared. RESULTS: The
      angiographic success was reached by 97.4% in the TRA group compared with 100% in
      the TFA group (P = 0.02). The procedure success was achieved in 99.1% in the TRA
      group and 97.9% in the TFA group (P = 0.68). The incidence rates of in-hospital
      NACE (2.7% vs. 2.7%, P = 1.00) and 1-year MACE (11.5% vs. 12.0%, P = 0.88) were
      similar between TRA and TFA. Meanwhile, TRA was associated with a lower rate of
      Bleeding Academic Research Consortium >=2 bleeding (P = 0.02). In patients
      undergoing graft PCI, the procedure success was similar between TRA and TFA
      (100.0% vs. 98.7%, P = 1.00). The procedure time (25.0 min vs. 27.5 min, P =
      0.53) was also similar. No significant difference was detected between TRA and
      TFA in terms of in-hospital NACE (0 vs. 0, P = 1.00) and 1-year MACE (21.4% vs.
      10.3%, P = 0.19). CONCLUSIONS: Compared with TFA, TRA had lower angiographic
      success but had a similar procedure success in post-CABG patients. TRA was also
      associated with decreased bleeding and shortened hospital stay.

PMID- 25758270
TI  - Nine-month angiographic and two-year clinical follow-up of novel biodegradable
      polymer arsenic trioxide-eluting stent versus durable-polymer sirolimus-eluting
      stent for coronary artery disease.
AB  - BACKGROUND: Despite great reduction of in-stent restenosis, first-generation drug
      eluting stents (DESs) have increased the risk of late stent thrombosis due to
      delayed endothelialization. Arsenic trioxide, a natural substance that could
      inhibit cell proliferation and induce cell apoptosis, seems to be a promising
      surrogate of sirolimus to improve DES performance. This randomized controlled
      trial was to evaluate the efficacy and safety of a novel arsenic trioxide-eluting
      stent (AES), compared with traditional sirolimus-eluting stent (SES). METHODS:
      Patients with symptoms of angina pectoris were enrolled and randomized to AES or
      SES group. The primary endpoint was target vessel failure (TVF), and the second
      endpoint includes rates of all-cause death, cardiac death or myocardial
      infarction, target lesion revascularization (TLR) by telephone visit and late
      luminal loss (LLL) at 9-month by angiographic follow-up. RESULTS: From July 2007
      to 2009, 212 patients were enrolled and randomized 1:1 to receive either AES or
      SES. At 2 years of follow-up, TVF rate was similar between AES and SES group
      (6.67% vs. 5.83%, P = 0.980). Frequency of all-cause death was significantly
      lower in AES group (0 vs. 4.85%, P = 0.028). There was no significant difference
      between AES and SES in frequency of TLR and in-stent restenosis, but greater in
      stent LLL was observed for AES group (0.29 +/- 0.52 mm vs. 0.10 +/- 0.25 mm, P =
      0.008). CONCLUSIONS: After 2 years of follow-up, AES demonstrated comparable
      efficacy and safety to SES for the treatment of de novo coronary artery lesions.

PMID- 25758271
TI  - Comparing of light transmittance aggregometry and modified thrombelastograph in
      predicting clinical outcomes in Chinese patients undergoing coronary stenting
      with clopidogrel.
AB  - BACKGROUND: Several platelet function tests are currently used to measure
      responsiveness to antiplatelet therapy. This study was to compare two tests,
      light transmittance aggregometry (LTA) and modified thrombelastography (mTEG),
      for predicting clinical outcomes in Chinese patients after percutaneous coronary
      intervention (PCI). METHODS: Prospective, observational, single-center study of
      789 Chinese patients undergoing PCI was enrolled. This study was investigated the
      correlations between the two tests and performed receiver operating
      characteristic curve (ROC) analysis for major adverse cardiovascular events
      (MACEs) at 1-year follow-up. RESULTS: MACEs occurred in 32 patients (4.1%).
      Correlations were well between the two tests in the adenosine diphosphate induced
      platelet reactivity (Spearman r = 0.733, P < 0.001). ROC-curve analysis
      demonstrated that LTA (area under the curve [AUC]: 0.677; 95% confidence interval
      [CI]: 0.643-0.710; P = 0.0009), and mTEG (AUC: 0.684; 95% CI: 0.650-0.716; P =
      0.0001) had moderate ability to discriminate between patients with and without
      MACE. MACE occurred more frequently in patients with high on-treatment platelet
      reactivity (HPR) when assessed by LTA (7.4% vs. 2.7%; P < 0.001), and by TEG
      (6.7% vs. 2.6%; P < 0.001). Kaplan-Meier analysis demonstrated that HPR based on
      the LTA and mTEG was associated with almost 3-fold increased risk of MACE at 1
      year follow-up. CONCLUSIONS: The correlation between LTA and mTEG is relatively
      high in Chinese patients. HPR measured by LTA and mTEG were significantly
      associated with MACE in Chinese patients undergoing PCI.

PMID- 25758272
TI  - Transcatheter closure of atrial septal defects improves cardiac remodeling and
      function of adult patients with permanent atrial fibrillation.
AB  - BACKGROUND: Permanent atrial fibrillation (AF) is the most common form of
      dysrhythmia associated with atrial septal defects (ASDs) in patients older than
      40 years. However, little is known about cardiac remodeling after transcatheter
      closure in patients with permanent AF. This study was designed to compare cardiac
      events and remodeling effects after transcatheter closure in such patients.
      METHODS: Clinical data of 289 adult patients older than 40 years who underwent
      ASD closure at our center were analyzed retrospectively. Of them, 63 patients
      with permanent AF were assigned to the case group, and the other 226 patients
      without permanent AF were assigned to the control group. Cardiac events and
      changes in left and right cardiac cavity dimensions before the procedure and 6
      months after the procedure were compared between the two groups. RESULTS:
      Patients in the case group were significantly older than those in the control
      group. The right ventricular (RV) volume and right atrial (RA) volume were
      decreased significantly in both the groups during a median follow-up period of 6
      months after closure (P < 0.001). The left atrial dimensions, left ventricular
      end-systolic dimensions, left ventricular end-diastolic dimensions and left
      ventricular ejection fraction showed no significant change before and after the
      procedure in both the groups. Changes of the RV volume and RA volume in the case
      group were significantly smaller than those in the control group (P = 0.005 and P
      < 0.001). The New York Heart Association cardiac function was improved in both
      the groups during the 6 months follow-up period. CONCLUSIONS: The transcatheter
      closure of ASD can improve the cardiac remodeling and cardiac function in
      patients with or without AF.

PMID- 25758273
TI  - Short-term rosuvastatin treatment for the prevention of contrast-induced acute
      kidney injury in patients receiving moderate or high volumes of contrast media: a
      sub-analysis of the TRACK-D study.
AB  - BACKGROUND: Current randomized trials have demonstrated the effects of short-term
      rosuvastatin therapy in preventing contrast-induced acute kidney injury (CIAKI).
      However, the consistency of these effects on patients administered different
      volumes of contrast media is unknown. METHODS: In the TRACK-D trial, 2998
      patients with type 2 diabetes and concomitant chronic kidney disease (CKD) who
      underwent coronary/peripheral arterial angiography with or without percutaneous
      intervention were randomized to short-term (2 days before and 3 days after
      procedure) rosuvastatin therapy or standard-of-care. This prespecified analysis
      compared the effects of rosuvastatin versus standard therapy in patients exposed
      to (moderate contrast volume [MCV], 200-300 ml, n = 712) or (high contrast volume
      [HCV], >= 300 ml, n = 220). The primary outcome was the incidence of CIAKI. The
      secondary outcome was a composite of death, dialysis/hemofiltration or worsened
      heart failure at 30 days. RESULTS: Rosuvastatin treatment was associated with a
      significant reduction in CIAKI compared with the controls (2.1% vs. 4.4%, P =
      0.050) in the overall cohort and in patients with MCV (1.7% vs. 4.5%, P = 0.029),
      whereas no benefit was observed in patients with HCV (3.4% vs. 3.9%, P = 0.834).
      The incidence of secondary outcomes was significantly lower in the rosuvastatin
      group compared with control group (2.7% vs. 5.3%, P = 0.049) in the overall
      cohort, but it was similar between the patients with MCV (2.0% vs. 4.2%, P =
      0.081) or HCV (5.1% vs. 8.8%, P = 0.273). CONCLUSIONS: Periprocedural short-term
      rosuvastatin treatment is effective in reducing CIAKI and adverse clinical events
      for patients with diabetes and CKD after their exposure to a moderate volume of
      contrast medium.

PMID- 25758274
TI  - Short-term safety and efficiency of cryoablation for renal sympathetic
      denervation in a swine model.
AB  - BACKGROUND: Renal sympathetic nerves are involved in the reflective activation of
      the sympathetic nervous system in circulatory control. Catheter-based renal
      denervation (RDN) ameliorated treatment-resistant hypertension safely, but 10%
      20% of treated patients are nonresponders to radiofrequency denervation. The
      purpose of this study was to investigate the safety and efficiency of
      cryoablation for sympathetic denervation in a swine model and to explore a new
      way of RDN. METHODS: Seven swines randomly assigned to two groups: Renal
      cryoablation (CR) group and control group. The control group underwent renal
      angiogram only. The CR group underwent renal angiogram plus bilateral renal
      cryoablation. Renal angiograms via femoral were performed before denervation,
      after denervation and prior to the sacrifice to access the diameter of renal
      arterial and the pressure of aorta abdominalis. Euthanasia of the swine was
      performed on 28-day to access norepinephrine (NE) changes of the renal cortex and
      the changes of renal nerves. RESULTS: Cryoablation did not induce severe
      complications at any time point. There was no significant change in diameter of
      renal artery. CR reduced systolic blood pressure (BP) from 145.50 +/- 9.95 mmHg
      at baseline to 119.00 +/- 14.09 mmHg. There was a slight but insignificant
      decrease in diastolic BP. The main nerve changes at 28-day consisted of necrosis
      with perineurial fibrosis at the site of CR exposure in conjunction with the
      nerve vacuolation. Compared with the control group, renal tissue NE of CR group
      decreased by 89.85%. CONCLUSIONS: Percutaneous catheter-based cryoablation of the
      renal artery is safe. CR could effectively reduce NE storing in the renal cortex,
      and the efficiency could be maintained 28-day at least.

PMID- 25758275
TI  - Ulnar artery compression: a feasible and effective approach to prevent the radial
      artery occlusion after coronary intervention.
AB  - BACKGROUND: Radial artery (RA) occlusion (RAO) is not rare in patients undergoing
      coronary intervention by transradial approach (TRCI). Predictors of and
      prevention from RAO have not been systematically studied. This study aimed to
      analyze the risk factors of the weakness of RA pulsation (RAP) and its predictive
      value for RAO after TRCI, and simultaneously to describe a feasible and effective
      approach to maintain RA patency. METHODS: Between June 2006 and March 2010, all
      patients who underwent TRCI were classified according to the weakness of RAP
      after removing compression bandage with confirmation by Doppler ultrasound for
      the first 30 consecutive patients. Among a total of 2658 patients studied, 187
      (7%) patients having a weaker RAP were prospectively monitored. At 1 h after
      bandage removal, the ulnar artery in puncture side of all patients was blocked
      with manual compression to favor brachial and collateral artery blood flow
      through the RA until a good RAP was restored. The primary analysis was the
      occurrence of RAO. RESULTS: Doppler ultrasound demonstrated the significant
      reduction of both systolic velocity (61.24 +/- 3.95 cm/s vs. 72.31 +/- 3.57 cm/s)
      and diastolic velocity (1.83 +/- 0.32 cm/s vs. 17.77 +/- 3.97 cm/s) in RA at
      access side as compared to the contralateral RA (all P < 0.001), but these
      velocities in ipsilateral ulnar artery (81.2 +/- 2.16 cm/s and 13.1 +/- 2.86
      cm/s, respectively) increased profoundly. The average time of ulnar artery
      compression was 4.1 +/- 1.2 h (ranged 2.5-6.5 h). There were two patients
      experienced persistent RAO with a success rate of 98.9% and RAO in 0.075% of
      patients after ulnar artery compression was applied. The pulsation of the ulnar
      artery after compression was removed had not been influenced by the compression.
      CONCLUSIONS: After intervention using TRCI approach, the presence of a weaker RAP
      is an indicator of imminent RAO. The continuing compression of ipsilateral ulnar
      artery is an effective approach to maintain RA patency.

PMID- 25758276
TI  - Effects of guideline-based hypertension management in rural areas of Guangdong
      Province.
AB  - BACKGROUND: Despite the improvement in the health care industry, the rates of
      undetected, untreated, and uncontrolled hypertension (HTN) are still very high,
      especially in rural areas of China. The aim of this study was to investigate the
      efficacy and efficiency of a guideline-based HTN management (novel therapy) in
      population of rural areas of Guangdong Province. METHODS: Totally, 3113 patients
      with essential HTN in a rural area of Guangdong Province were enrolled and
      assigned to two groups, named traditional (n = 372) and novel therapeutic (n =
      2741) groups, respectively. Patients in the traditional group were treated
      routinely, and patients in the novel group were treated in a novel model
      characterized by regular educational programs for hypertensive populations, close
      monitoring of blood pressure in combination with finely tuned antihypertensive
      medications, strict implementation of lifestyle modification and improving
      medical knowledge and skill of local medical staff efficiently. After 2 years of
      follow-up, primary endpoints including magnitude of systolic and diastolic blood
      pressures (SBP and DBP) decrease, treated and controlled rates, as well as
      secondary endpoints, were evaluated in both groups. RESULTS: Initially, the
      treated rate was significantly higher in traditional group than that of novel
      group (71.15% vs. 64.99%, P < 0.05), while the controlled rates were comparable
      and insignificant difference between baseline BP in both groups (31.07% vs.
      26.88%, P > 0.05). Four variables were significantly different, namely smoking
      rate, daily vegetable consumption (VC), and serum levels of low-density
      lipoprotein-cholesterol and fasting blood glucose between these two groups. After
      2 years of follow-up, decreases in SBP and DBP were more prominent in the novel
      group (P < 0.001). Treated and controlled rates in both groups were both
      increased. Nevertheless, in comparison to the traditional group, controlled rate
      increased more significantly in the novel group (64.31% vs. 37.85%, P < 0.001).
      Variables indicating lifestyle modification such as high sodium consumption,
      percentages of alcohol abuse, daily VC were profoundly improved in the novel
      group. CONCLUSIONS: The guideline-based HTN management implemented in the current
      study was beneficial for HTN control in rural areas of Guangdong Province.

PMID- 25758277
TI  - Retroperitoneal fibrosis: a retrospective clinical data analysis of 30 patients
      in a 10-year period.
AB  - BACKGROUND: Retroperitoneal fibrosis (RPF) is an uncommon disease that is
      characterized by development of fibrosclerotic tissues involving retroperitoneal
      structures. This study aimed to investigate the clinical features of 30 patients
      with RPF in a single center in Beijing in a 10-year period. METHODS: We
      retrospectively analyzed clinical data on demographic characteristics, clinical
      manifestations, laboratory findings, radiological findings, modalities of
      treatments, outcomes and prognosis of 30 patients with RPF. Patients were treated
      in Beijing Chao-Yang Hospital between January 2003 and December 2013. RESULTS:
      The mean age of patients with RPF was 56.7 +/- 14.4 years. Twenty-three patients
      were men and seven patients were women. Acute phase reactants were elevated in
      most patients. Rheumatic factor was positive in 4/25 (16.0%) patients, and
      antinuclear antibody was positive in 6/22 (27.3%) patients. Elevation of IgG4 was
      observed in 9/22 (40.9%) patients. The most common type was I + III (n = 13),
      followed by I + II + III (n = 12). Five patients undertook an 18 F-fluoro-deoxy-D
      glucose positron emission tomography examination and increased uptake was
      detected in four patients. Eight patients received combination therapy with
      glucocorticoids and tamoxifen. Surgical intervention treatments included
      intraureteral double-J stent implantation (n = 26), percutaneous nephrostomy (n =
      2), open ureterolysis and intraperitonealization of the ureters (n = 5) and
      laparoscopic ureterolysis and intraperitonealization of the ureters (n = 5).
      Three patients underwent hemodialysis because of renal failure. CONCLUSIONS:
      Clinical characteristics of RPF patients in our study are similar to those
      previously reported. Steroids and immunosuppressive therapy combined with
      ureterolysis could be a viable choice of treatment for RPF. More prospective,
      multi-center studies with a longer follow-up are warranted.

PMID- 25758278
TI  - Is early-onset in major depression a predictor of specific clinical features with
      more impaired social function?
AB  - BACKGROUND: Early-onset major depressive disorder (MDD) (EOD) is often
      particularly malignant due to its special clinical features, accompanying
      impaired social function, protracted recovery time, and frequent recurrence. This
      study aimed to observe the effects of age onset on clinical characteristics and
      social function in MDD patients in Asia. METHODS: In total, 547 out-patients aged
      18-65 years who were from 13 study sites in five Asian countries were included.
      These patients had MDD diagnose according to the Diagnostic and Statistical
      Manual of Mental Disorders, 4 th Edition criteria. Clinical features and social
      function were assessed using Symptom Checklist-90-revised (SCL-90-R) and Sheehan
      Disability Scale (SDS). Quality of life was assessed by a 36-item Short-form
      Health Survey (SF-36). Analyses were performed using a continuous or dichotomous
      (cut-off: 30 years) age-of-onset indicator. RESULTS: Early-onset MDD (EOD, <30
      years) was associated with longer illness (P = 0.003), unmarried status (P <
      0.001), higher neuroticism (P <= 0.002) based on the SCL-90-R, and more limited
      social function and mental health (P = 0.006, P = 0.007) based on the SF-36 and
      SDS. The impairment of social function and clinical severity were more prominent
      at in-patients with younger onset ages. Special clinical features and more
      impaired social function and quality of life were associated with EOD, as in
      western studies. CONCLUSIONS: EOD often follows higher levels of neuroticism. Age
      of onset of MDD may be a predictor of clinical features and impaired social
      function, allowing earlier diagnosis and treatment.

PMID- 25758279
TI  - Comparison of two dose-response relationship of noise exposure evaluation results
      with high frequency hearing loss.
AB  - BACKGROUND: Complex noise and its relation to hearing loss are difficult to
      measure and evaluate. In complex noise measurement, individual exposure results
      may not accurately represent lifetime noise exposure. Thus, the mean L Aeq,8 h
      values of individuals in the same workgroup were also used to represent L Aeq,8 h
      in our study. Our study aimed to explore whether the mean exposure levels of
      workers in the same workgroup represented real noise exposure better than
      individual exposure levels did. METHODS: A cross-sectional study was conducted to
      establish a model for cumulative noise exposure (CNE) and hearing loss in 205
      occupational noise-exposed workers who were recruited from two large automobile
      manufacturers in China. We used a personal noise dosimeter and a questionnaire to
      determine the workers' occupational noise exposure levels and exposure times,
      respectively. A qualified audiologist used standardized audiometric procedures to
      assess hearing acuity after at least 16 h of noise avoidance. RESULTS: We
      observed that 88.3% of workers were exposed to more than 85 dB(A) of occupational
      noise (mean: 89.3 +/- 4.2 dB(A)). The personal CNE (CNEp) and workgroup CNE
      (CNEg) were 100.5 +/- 4.7 dB(A) and 100.5 +/- 2.9 dB(A), respectively. In the
      binary logistic regression analysis, we established a regression model with high
      frequency hearing loss as the dependent variable and CNE as the independent
      variable. The Wald value was 5.014 with CNEp as the independent variable and
      8.653 with CNEg as the independent variable. Furthermore, we found that the
      figure for CNEg was more similar to the stationary noise reference than CNEp was.
      The CNEg model was better than the CNEp model. In this circumstance, we can
      measure some subjects instead of the whole workgroup and save manpower.
      CONCLUSIONS: In a complex noise environment, the measurements of average noise
      exposure level of the workgroup can improve the accuracy and save manpower.

PMID- 25758280
TI  - Safety and efficacy of a novel technique in the use of fractional flow reserve in
      complex coronary artery lesions.
AB  - BACKGROUND: Fractional flow reserve (FFR) has become an increasingly important
      index when making decisions with respect to revascularization of coronary artery
      stenosis. However, the pressure guidewire used in obtaining FFR measurements is
      difficult to control and manipulate in certain complex coronary artery lesions,
      resulting in increased fluoroscopy time and contrast dye usage. This study
      examined a novel (NOV) technique for obtaining FFR measurements in hope of easing
      the difficulties associated with evaluating and treating complex coronary artery
      lesions. METHODS: Fifty-six patients with complex coronary artery lesions were
      assigned to a conventional (CON) FFR technique group or a NOV FFR technique
      group. The NOV technique involved the use of a balloon and wire exchange within
      the coronary artery. The fluoroscopy time, contrast dye usage, and FFR-related
      complications were assessed after completing the FFR measurement procedure for
      each patient. RESULTS: The median time required for fluoroscopy in the NOV
      technique group was significantly less than that in the CON technique group;
      additionally, lesser amounts of contrast dye were used in the NOV technique group
      (both P < 0.05). The NOV technique was successfully performed in thirty patients,
      without any FFR-related complications. However, the CON technique failed in three
      patients, including two who experienced coronary artery spasms (P > 0.05).
      CONCLUSIONS: Compared to the CON technique used for measuring FFR, the new
      technique reduced the fluoroscopy time and amount of contrast dye used when
      evaluating complex coronary artery lesions. The new technique did not increase
      the risk of operation or decrease the success rate.

PMID- 25758281
TI  - Transjugular intrahepatic portosystemic shunt versus surgical shunting in the
      management of portal hypertension.
AB  - BACKGROUND: The purpose of this article was to clarify the optimal management
      concerning transjugular intrahepatic portosystemic shunts (TIPSs) and surgical
      shunting in treating portal hypertension. METHODS: All databases, including CBM,
      CNKI, WFPD, Medline, EMBASE, PubMed and Cochrane up to February 2014, were
      searched for randomized controlled trials (RCTs) comparing TIPS with surgical
      shunting. Four RCTs, which were extracted by two independent investigators and
      were evaluated in postoperative complications, mortality, 2- and 5-year survival,
      hospital stay, operating time and hospitalization charges. RESULTS: The morbidity
      in variceal rehemorrhage was significantly higher in TIPS than in surgical shunts
      (odds ratio [OR] = 7.45, 95% confidence interval[CI]: (3.93-14.15), P < 0.00001),
      the same outcomes were seen in shunt stenosis (OR = 20.01, 95% CI: (6.67-59.99),
      P < 0.000001) and in hepatic encephalopathy (OR = 2.50, 95% CI: (1.63-3.84), P <
      0.0001). Significantly better 2-year survival (OR = 0.66; 95% CI: (0.44-0.98), P
      = 0.04) and 5-year survival (OR = 0.44; 95% CI: (0.30-0.66), P < 0.00001) were
      seen in patients undergoing surgical shunting compared with TIPS. CONCLUSIONS:
      Compared with TIPS, postoperative complications and survival after surgical
      shunting were superior for patients with portal hypertension. Application of
      surgical shunting was recommended for patients rather than TIPS.

PMID- 25758282
TI  - Effects of immunosuppressants on immune response to vaccine in inflammatory bowel
      disease.
AB  - OBJECTIVE: To evaluate the response rate to vaccination in different treatment
      groups (nonimmunosuppressants and immunosuppressants). DATA SOURCES: We completed
      an online systematic search using PubMed to identify all articles published in
      English between January 1990 and December 2013 assessing the effect of the
      response rate to vaccination in different treatment groups (with and without
      immunomodulators). The following terms were used: "inflammatory bowel disease
      (IBD)" OR "Crohn's disease" OR "ulcerative colitis" AND ("vaccination" OR
      "vaccine") AND ("corticosteroids" OR "mercaptopurine" OR "azathioprine" OR
      "methotrexate [MTX]") AND "immunomodulators." STUDY SELECTION: The inclusion
      criteria of articles were that the studies: (1) Randomized controlled trials
      which included patients with a diagnosis of IBD (established by standard
      clinical, radiographic, endoscopic, and histologic criteria); (2) exposed
      patients received immunomodulators for maintenance (weight-appropriate doses of 6
      mercaptopurine/azathioprine or within 3 months of stopping, 15 mg or more MTX per
      week or within 3 months of stopping; (3) exposed patients received
      nonimmunomodulators (no therapy, antibiotics only, mesalazine only, biological
      agent only such as infliximab, adalimumab, certolizumab or natalizumab or within
      3 months of stopping one of these agents). The exclusion criteria of articles
      were that the studies: (1) History of hepatitis B virus (HBV), influenza or
      streptococcus pneumoniae infection; (2) patients who had previously been
      vaccinated against HBV, influenza or streptococcus pneumoniae; (3) any medical
      condition known to cause immunosuppression (e.g. chronic renal failure and human
      immunodeficiency virus infection); (4) individuals with positive hepatitis
      markers or liver cirrhosis; (5) patients with a known allergy to eggs or other
      components of the vaccines and (6) pregnancy. RESULTS: Patients treated with
      immunomodulators were associated with lower response rates to vaccination.
      CONCLUSIONS: Immunomodulators may impair the immune response to vaccination in
      patients with IBD. Vaccination should be made at the time of diagnosis or before
      starting immunosuppressed therapy.

PMID- 25758283
TI  - Tackling China's noncommunicable diseases: shared origins, costly consequences
      and the need for action.

PMID- 25758284
TI  - An infrasellar craniopharyngioma involving the sphenoid sinus and clivus.

PMID- 25758285
TI  - Continuous mechanical chest compression-assisted percutaneous coronary
      intervention in a patient with cardiac arrest complicating acute myocardial
      infarction.

PMID- 25758286
TI  - Apical sphere ventricular aneurysm with severe endocardium calcification after
      old anterior myocardial infarction.

PMID- 25758287
TI  - Concurrence of sarcoidosis and Takayasu aortitis.

PMID- 25758288
TI  - The concurrent use of three implicit measures (eye movements, pupillometry, and
      event-related potentials) to assess receptive vocabulary knowledge in normal
      adults.
AB  - Recent years have seen the advent and proliferation of the use of implicit
      techniques to study learning and cognition. One such application is the use of
      event-related potentials (ERPs) to assess receptive vocabulary knowledge. Other
      implicit assessment techniques that may be well-suited to other testing
      situations or to use with varied participant groups have not been used as widely
      to study receptive vocabulary knowledge. We sought to develop additional implicit
      techniques to study receptive vocabulary knowledge that could augment the
      knowledge gained from the use of the ERP technique. Specifically, we used a
      simple forced-choice paradigm to assess receptive vocabulary knowledge in normal
      adult participants using eye movement monitoring (EM) and pupillometry. In the
      same group of participants, we also used an N400 semantic incongruity ERP
      paradigm to assess their knowledge of two groups of words: those expected to be
      known to the participants (high-frequency, familiar words) and those expected to
      be unknown (low-frequency, unfamiliar words). All three measures showed reliable
      differences between the known and unknown words. EM and pupillometry thus may
      provide insight into receptive vocabulary knowledge similar to that from ERPs.
      The development of additional implicit assessment techniques may increase the
      feasibility of receptive vocabulary testing across a wider range of participant
      groups and testing situations, and may make the conduct of such testing more
      accessible to a wider range of researchers, clinicians, and educators. 

PMID- 25758289
TI  - Nursing practice environment: a strategy for mental health nurse retention?
AB  - Historically, mental health services have faced challenges in their ability to
      attract and retain a competent nursing workforce in the context of an overall
      nursing shortage. The current economic downturn has provided some respite;
      however, this is likely to be a temporary reprieve, with significant nursing
      shortages predicted for the future. Mental health services need to develop
      strategies to become more competitive if they are to attract and retain skilled
      nurses and avoid future shortages. Research demonstrates that creating and
      maintaining a positive nursing practice environment is one such strategy and an
      important area to consider when addressing nurse retention. This paper examines
      the impact the nursing practice environment has on nurse retention within the
      general and mental health settings. Findings indicate, that while there is a
      wealth of evidence to support the importance of a positive practice environment
      on nurse retention in the broader health system, there is little evidence
      specific to mental health. Further research of the mental health practice
      environment is required. 

PMID- 25758290
TI  - Human papillomavirus (HPV) types 16 and 18 in liquid-based cervical cytology
      samples.
AB  - Human papillomavirus (HPV) DNA testing is replacing cervical cytology as a
      primary cervical cancer screening tool. The aim of this study was to determine
      the frequency of occurrence of HPV types 16 and 18 in liquid-based cytology (LBC)
      cervical samples in our set-up. This study comprised of 302 LBC cervical samples.
      HPV 16 and HPV 18 were detected by polymerase chain reaction (PCR), and the
      results were compared between normal (n = 155), inflammatory (n = 99), squamous
      (n = 37) and glandular abnormalities (n = 11). Of our patient cohort, 73.8 % was
      <=40 years old. We found HPV 16 DNA in 91/302 (30.1 %) cases and HPV 18 DNA in
      21/302 (6.95 %). HPV types 16 and 18 were detected in 25.8 and 4.5 %
      cytologically normal samples, respectively. HPV 16 was positive in 29.3 % of
      inflammatory samples. Squamous cervical abnormalities were more often HPV
      positive (HPV 16 in 48.6 %; HPV 18 in 29.7 %) than glandular abnormalities (36.4
      and 18.2 %, respectively). We found high-risk HPV DNA in more than one third of
      the tested women. A good number of these HPV-positive cases were negative in
      cervical cytology.

PMID- 25758291
TI  - Extracorporal rat cecum mesothelium desiccation-induced by CO2 insufflation: is
      there a clinical sense of this adhesion formation model?

PMID- 25758292
TI  - Fabrication of SnO2-reduced graphite oxide monolayer-ordered porous film gas
      sensor with tunable sensitivity through ultra-violet light irradiation.
AB  - A new graphene-based composite structure, monolayer-ordered macroporous film
      composed of a layer of orderly arranged macropores, was reported. As an example,
      SnO2-reduced graphite oxide monolayer-ordered macroporous film was fabricated on
      a ceramic tube substrate under the irradiation of ultra-violet light (UV), by
      taking the latex microsphere two-dimensional colloid crystal as a template.
      Graphite oxide sheets dispersed in SnSO4 aqueous solution exhibited excellent
      affinity with template microspheres and were in situ incorporated into the pore
      walls during UV-induced growth of SnO2. The growing and the as-formed SnO2, just
      like other photocatalytic semiconductor, could be excited to produce electrons
      and holes under UV irradiation. Electrons reduced GO and holes adsorbed
      corresponding negative ions, which changed the properties of the composite film.
      This film was directly used as gas-sensor and was able to display high
      sensitivity in detecting ethanol gas. More interestingly, on the basis of SnO2
      induced photochemical behaviours, this sensor demonstrated tunable sensitivity
      when UV irradiation time was controlled during the fabrication process and post
      in water, respectively. This study provides efficient ways of conducting the in
      situ fabrication of a semiconductor-reduced graphite oxide film device with
      uniform surface structure and controllable properties. 

PMID- 25758293
TI  - The effect of methimazole-induced postnatal hypothyroidism on the retinal
      maturation and on the Sirtuin 2 level.
AB  - PURPOSE: To investigate the effect of methimazole-induced postnatal
      hypothyroidism on the retinal maturation and to study Sirtuin 2 (SIRT2) level in
      the hypothyroidic rat retina. METHODS: Twenty newborn Wistar albino rat pups were
      used in this prospective, randomized study. Wistar albino rats, weight 250-300 g,
      were impregnated (without addition of any drug) and were fed normally. Rat pups
      were randomly divided into two groups and were fed with breast milk. After
      weaning till they were 90 days of age, rat pups received the same water as their
      lactating mothers drank. Group 1 (methimazole (MMI)-induced hypothyroidy group),
      rats were given MMI-water, whereas, in Group 2, normal tap water. When the pups
      were 90 days of age, 20 rat pups were decapitated and the eyes were isolated.
      Eyes were investigated using histological, histomorphometric and
      immunohistochemistrical techniques. RESULTS: No histological difference was seen
      between the groups stained with hematoxylin and eosin. In both groups the retinal
      layer structures and cells were observed as normal. The examples in the groups
      had a normal distribution for retinal thickness (pixel) measure. The mean value
      (mean +/- std. deviation) was 554.7 +/- 228.4 in the control group and 494.7 +/-
      129.4 in the hypothyroidy group. There was no significance between the groups in
      terms of retinal thickness (p = 0.231). However, immunohistochemistry revealed
      that SIRT2 was weaker stained in the ganglion cell layer and visual cell layer in
      the hypothyroidy group compared to the control group. CONCLUSION: Postnatal
      hypothyroidism altered the retinal cytoarchitecture and layering which are
      regulated by thyroid hormones (THs) during retinal maturation in the postnatal
      period. THs may act by the induction of the SIRT family proteins or through their
      receptors. Postnatal screenings for THs levels are very important to provide
      normal retinal development.

PMID- 25758294
TI  - Simultaneous measurement of methyl tert-butyl ether and tert-butyl alcohol in
      human serum by headspace solid-phase microextraction gas chromatography-mass
      spectrometry.
AB  - The abundant production of methyl tert-butyl ether (MTBE) and its widespread use
      have led to an increase in the potential for human exposure. This work described
      a simple, fast, sensitive, reliable and low-cost method for the simultaneous
      measurement of MTBE and its metabolite, tert-butyl alcohol (TBA) in human serum
      by headspace solid-phase microextraction gas chromatography-mass spectrometry.
      Extraction conditions were optimized and 40  degrees C, 10 min, 250 rpm and 0.3 g
      NaCl for a 1 mL sample were the optimal conditions. This method showed good
      analytical performance in terms of sensitivity with limits of detection in serum
      (1 mL) of 0.03 ug/L for MTBE and 0.05 ug/L for TBA, accuracy (mean recovery
      values) from 75.8% to 85.8%, precision (relative standard deviations) <10% and
      sample stability (biodegradation) <10% after 28 days. A verification experiment
      proved the reproducibility and stability of this method as well. Finally the
      method was used to detect 212 specimens, and the internal dose levels for MTBE in
      human serum were presented in China.

PMID- 25758295
TI  - Benign paroxysmal positional vertigo: opportunities squandered.
AB  - Benign paroxysmal positional vertigo (BPPV) presentations are unique
      opportunities to simultaneously improve the effectiveness and efficiency of care.
      The test and treatment for BPPV--the Dix-Hallpike test (DHT) and the canalith
      repositioning maneuver (CRM), respectively--are supported by two evidence-based
      guidelines (American Academy of Otolaryngology--Head and Neck Surgery and
      American Academy of Neurology). With these processes, patients can be readily
      identified and treated at the bedside, quickly and without expensive tests.
      Patients randomized to the CRM have a cure rate of 80% at 24 h, compared to only
      10% of controls. Despite this large effect size, less than 10% of affected
      patients receive the treatment, which shows that the management of BPPV in
      routine care is suboptimal. Future research is necessary to disseminate and
      implement the DHT and the CRM into routine practice.

PMID- 25758296
TI  - Solvent effects on the structures and magnetic properties of two doubly
      interpenetrated metal-organic frameworks.
AB  - Two doubly interpenetrated coordination polymers [Co2(BDC)2(bpt)2].nSolvent based
      on dimeric secondary building units and crystallizing with distinct solvent
      molecules (-H2O and -MeOH for nSolvent = 2H2O and MeOH.H2O, respectively) were
      obtained by employing 1,4-benzenedicarboxylate (BDC) and 1H-3,5-bis(4-pyridyl)
      1,2,4-triazole) (bpt) as linkers. The structures consist of a square grid of
      dimers bridged by BDC and pillared by bpt. Thermogravimetry and PXRD indicate
      that the frameworks are stable and are retained up to 400  degrees C, but the
      structures are modified irreversibly. -H2O, high-symmetry Pna21, exhibits
      antiferromagnetic coupling within the dimer, while -MeOH, low-symmetry P21/n,
      exhibits ferromagnetic coupling. Upon desolvation, the -de and -de couplings are
      antiferromagnetic but reduced. Subsequent resolvation to -H2O and -MeOH resulted
      in a slight increase of the antiferromagnetic coupling without attaining the
      virgin states. The interesting difference of magnetic properties between -H2O and
      -MeOH, the solvated/desolvated phases, particularly at low temperature, indicates
      that there is a prominent solvent effect. 

PMID- 25758297
TI  - Another shout out for OSA! The association between voice performance, OSA, and
      CPAP therapy. Commentary on: The effect of OSAS and CPAP on voice performance by
      Antan D, Ozcan KM, Ikinciogullari A, et al.

PMID- 25758298
TI  - Evaluation of the Arabic version of STOP-Bang questionnaire as a screening tool
      for obstructive sleep apnea.
AB  - PURPOSE: Obstructive sleep apnea (OSA) is a sleep-related breathing disorder that
      is underdiagnosed. OSA is usually diagnosed by polysomnography (PSG) and, if
      untreated, could lead to life-threatening complications. Many screening
      questionnaires have been developed to screen and identify patients at high risk
      for OSA. This study aimed to evaluate and validate the Arabic version of Stop
      Bang questionnaire as a screening tool for patients with OSA symptoms referred to
      a sleep clinic. METHODS: All referred Arabic-speaking adult patients presenting
      to a Sleep Disorders Specialized Clinic in Al Ain for PSG were requested to
      complete an Arabic STOP-Bang questionnaire. A score of 3 or more out of a
      possible 8 was taken to indicate high risk for presence of OSA. These scores were
      then evaluated versus results from the overnight, monitored PSG. Apnea/hypopnea
      index (AHI) of >=5/h was considered for diagnosis of OSA. RESULTS: One hundred
      ninety-three sleep clinic patients were enrolled in this study. PSG was positive
      (AHI >=5) in 85 % of the studied population. STOP-Bang questionnaire was positive
      (>=3) in 87 % of the population. Reproducibility of STOP-Bang questionnaire was
      tested, and the intraclass correlation coefficient of the total score of STOP
      Bang questionnaire was 0.931 (95 % CI 0.834-0.972). The sensitivities of the STOP
      Bang screening tool for an AHI of >=5, >=15, and >=30 were 90, 96.75, and 99.70
      %, respectively, with negative predictive values (NPVs) of 36, 84, and 92 %,
      respectively. ROC curve was 0.77. CONCLUSION: The Arabic version of STOP-Bang
      questionnaire is an easy-to-use tool that can be implemented as a reliable, quick
      screening tool for OSA in patients referred to sleep clinic. It demonstrated high
      sensitivity and NPV especially for patients with moderate to severe OSA. We
      believe that this tool will help physicians to earlier identify cases at risk of
      OSA.

PMID- 25758300
TI  - Linchpin dienes: key building-blocks in the synthesis of polyenic frameworks.
AB  - A myriad of biologically active products incorporates polyenic frameworks. Among
      the syntheses developed to access these moieties, metal-catalyzed cross-couplings
      emerged as reactions of choice especially due to their high stereoselectivity.
      Particularly, the use of bifunctionalized compounds (linchpin reagents) allows a
      fast, modular and efficient access to polyenic chains. In this review, we will
      focus on the preparation of bifunctionalized dienes and on their utilization in
      the synthesis of polyenes. 

PMID- 25758299
TI  - Effect of sertraline on breathing in depressed patients without moderate-to
      severe sleep-related breathing disorders.
AB  - BACKGROUND: Previous studies have reported that selective serotonin reuptake
      inhibitors (SSRIs) might improve sleep-related breathing disorders (SRBDs).
      However, the effects of SSRIs on breathing are not evaluated in subjects without
      moderate-to-severe SRBDs. Further, many symptoms of depression and SRBDs overlap,
      and so, it is interesting whether there are interactions between breathing and
      psychopathologic symptoms during SSRI treatment for depression. METHODS: Data
      were taken from an open-label 8-week trial of sertraline in depressed patients
      with insomnia (n = 31). The depressed patients were administered 50 mg sertraline
      at 8 AM on the first day, and the dosage was subsequently titrated up to a
      maximum of 200 mg/day during the 8-week trial. All the patients were tested by
      repeated polysomnography (PSG) (baseline, 1st day, 14th day, 28th day, and 56th
      day). Sleep-disordered breathing events were categorized as apneas, hypopneas,
      and respiratory event-related arousals (RERAs). RESULTS: The clinical responses
      and PSG characteristics improved continuously during the 8-week trial. From the
      14th day on, the RERA index during all-night and non-rapid eye movement (NREM)
      sleep became stable and significantly higher than baseline and the first day
      (RERA index 7.3 +/- 2.2 at baseline, 7.3 +/- 2.5 on the 1st day, 4.4 +/- 1.9 on
      the 14th day, 3.9 +/- 1.3 on the 28th day, 4.2 +/- 2.0 on the 56th day, F = 5.71,
      P = 0.02; NREM-RERA index 6.2 +/- 2.0 at baseline, 6.3 +/- 2.3 on the 1st day,
      3.2 +/- 1.5 on the 14th day, 3.5 +/- 0.9 on the 28th day, 3.2 +/- 1.7 on the 56th
      day, F = 4.92, P = 0.03). Additionally, the NREM-apnea index showed a similar
      pattern to that of the RERA index and reached a significant difference between
      baseline (1.0 +/- 0.5) and the 14th day (0.5 +/- 0.4) (KW = 4.28, P = 0.047).
      Compared to the no-improvement group, the improvement group with a decreasing
      score rate of the respiratory disturbance index (RDI) greater than or equal to 
      50 % had a more positive decreasing score rate of slow wave sleep (SWS) (439.0 +/
      78.2 vs 373.2 +/- 77.9 %, T = 3.46, P = 0.04) and a more negative decreasing
      score rate on the arousal index (-43.7 +/- 16.7 vs -26.6 +/- 9.7 %, T = 9.16, P =
      0.01), Pittsburgh Sleep Quality Index (PSQI) scores (-65.1 +/- 33.7 vs -49.6 +/-
      21.4 %, T = 4.74, P = 0.05), and Epworth Sleepiness Scale (ESS) scores (-55.7 +/-
      21.3 vs -36.4 +/- 17.5 %, T = 6.44, P = 0.02). DISCUSSION: This research
      indicates that SRBDs could be improved to some extent by sertraline treatment,
      which might be more common in patients with relatively more severe sleep
      disordered breathing (e.g., RDI >= 10 in the current study). Although the
      sertraline-induced SRBD improvement seems not to have a significant clinical
      effect, the SRBD improvement group with decreasing score rate of RDI greater than
      or equal to -50 % has better subjective and objective sleep aspects than the no
      improvement group. Thus, the fact that the SRBDs' improvement was related to
      SSRIs might have a potential clinical benefit in the antidepressant treatment.

PMID- 25758301
TI  - [Should knowledge of BRCA1 status impact the choice of chemotherapy in metastatic
      breast cancer: a review].
AB  - BRCA1 and BRCA2 mutations account for 40% of cancer predisposition gene mutations
      identified in the current French diagnostic setting. The proteins encoded by
      these genes are implicated in DNA repair pathways. As a result, loss of BRCA1 or
      BRCA2 function may modify chemo-sensitivity. This literature review aims to
      determine whether BRCA1 mutation status should influence the choice of systemic
      treatment in breast cancer. Fourteen articles and four abstracts from 12
      retrospective analyses and 6 prospective studies were identified in the
      literature review. CMF-type and taxane-based protocols appear to be
      insufficiently effective, while anthracycline activity does not seem to be
      affected by BRCA1 status. BRCA1-mutated tumours appear to be highly sensitive to
      platinum, in both the neoadjuvant and metastatic setting. Olaparib, a PARP
      inhibitor, has only been evaluated in one study in metastatic patients, with
      promising results. The presence of a BRCA1 mutation can lead to an adaptation of
      therapies in the metastatic stages in breast cancer. The rapid identification of
      BRCA1 mutations and the adaptation of treatment according to this status in the
      (neo)adjuvant setting is likely to become a reality in the coming years. 

PMID- 25758302
TI  - Experience from therapeutic drug monitoring and gender aspects of gabapentin and
      pregabalin in clinical practice.
AB  - PURPOSE: Gabapentin and pregabalin are antiepileptic drugs (AEDs) with epilepsy
      and neuropathic pain indications. The purpose of this study was to investigate
      pharmacokinetic variability of gabapentin and pregabalin and indications for
      therapeutic drug monitoring (TDM) in clinical practice with focus on gender
      aspects. METHOD: Anonymous data from routine TDM-service at the National Center
      for Epilepsy regarding serum concentration measurements of gabapentin and
      pregabalin, 2009-2013, were utilised. All included samples were drug-fasting in
      the morning at steady-state. RESULTS: In total, 356 patients were included;
      gabapentin 189 (66% women), average age 53 years and pregabalin 167 (56% women),
      average age 50 years. For gabapentin, mean serum concentration/dose(C/D)-ratio
      was similar across genders. Only 13% of the patients had concentrations above the
      lower limit of the reference range (70-120 MUmol/L), which indicates a need for
      reevaluation of the reference range. For pregabalin, the C/D-ratio in women
      (0.08+/-0.06) was 42% higher than in men (0.056+/-0.05; p<0.05). The
      pharmacokinetic variability (C/D-ratio) was >100-fold for both gabapentin and
      pregabalin. An indication of use (epilepsy/pain/other) was stated in only 26% of
      the cases (n=94). Epilepsy was assumed as indication when other AEDs were also
      measured (50% of patients). This was similar for both genders and for both AEDs.
      Indications for TDM were stated in 155 cases (44%) and were similar for
      gabapentin and pregabalin. CONCLUSION: Gabapentin and pregabalin are more used in
      women than in men, and routine use of TDM is most common in patients with
      epilepsy. Pharmacokinetic variability is extensive, highlighting a need for
      individualisation of therapy regardless of indication.

PMID- 25758303
TI  - Hydrosilylation of ketones, imines and nitriles catalysed by electrophilic
      phosphonium cations: functional group selectivity and mechanistic considerations.
AB  - The electrophilic phosphonium salt, [(C6 F5 )3 PF][B(C6 F5 )4 ], catalyses the
      efficient hydrosilylation of ketones, imines and nitriles at room temperature. In
      the presence of this catalyst, adding one equivalent of hydrosilane to a nitrile
      yields a silylimine product, whereas adding a second equivalent produces the
      corresponding disilylamine. [(C6 F5 )3 PCl][B(C6 F5 )4 ] and [(C6 F5 )3 PBr][B(C6
      F5 )4 ] are also synthesised and tested as catalysts. Competition experiments
      demonstrate that the reaction exhibits selectivity for the following functional
      groups in order of preference: ketone>nitrile>imine>olefin. Computational studies
      reveal the reaction mechanism to involve initial activation of the Si-H bond by
      its interaction with the phosphonium centre. The activated complex then acts
      cooperatively on the unsaturated substrate.

PMID- 25758304
TI  - Parental love.

PMID- 25758305
TI  - The developmental examination.

PMID- 25758306
TI  - Circumcision and the best interests of the child.

PMID- 25758307
TI  - Nature and psychological management of anxiety disorders in youth.
AB  - Anxiety disorders affect around 5% of the paediatric population at any given time
      and are associated with high social and personal impact. These disorders
      typically begin early in life, and children with anxiety disorders are at
      increased risk for a variety of later difficulties across the life-span. Although
      causes of anxiety in childhood are not fully understood, there is a strong
      heritable component. Additional risk factors include temperament, parent
      psychopathology, parent handling and peer interactions. Psychological treatments
      have demonstrated good efficacy with around 60% of anxious youth being in
      diagnostic remission immediately following treatment and a further 10% remitting
      over the following months. Because young people with anxiety disorders are among
      the least likely to seek appropriate help, paediatricians are in a unique
      position to identify anxious young people, educate families and recommend
      appropriate intervention. 

PMID- 25758308
TI  - Anxiety.

PMID- 25758309
TI  - What is that around the heart? Pneumopericardium.

PMID- 25758310
TI  - What is this sign? The 'central dot sign', associated with Caroli's disease and
      Caroli's syndrome.

PMID- 25758316
TI  - Management of severe faecal impaction in an adolescent with Duchenne muscular
      dystrophy (DMD) receiving palliative care.

PMID- 25758317
TI  - EUS-Guided Antegrade Balloon Dilation From Right Hepatic Duct Combined With
      Retrograde Rendezvous Stent Placement.

PMID- 25758318
TI  - Effective inpatient medication reconciliation: The 10 commandments.
AB  - Medication Reconciliation (MedRec) is the comprehensive process of medication
      verification, clarification and documentation in an effort to avoid medication
      errors. There are many reasons that contribute to the inadequacies of current day
      inpatient MedRec. Among these include the limited medical literacy of patients,
      communication between providers and teams of providers, and the intrinsic
      difficulties of medical charting. Although the best approach to inpatient MedRec
      is not known, the following outlines the 10 most important aspects, or
      "Commandments", for effective inpatient MedRec. The tenets are not listed in any
      particular order of importance. 

PMID- 25758320
TI  - Health care in small prisons: incorporating high-quality standards.
AB  - PURPOSE: In the past, health management in Geneva's six post-trial prisons had
      been variable and inconsistent. In 2008, the unit of penitentiary medicine of the
      Geneva University Hospitals was mandated to re-organize and provide health care
      at all six prison facilities. The specific aim of this paper is to outline the
      example as a practical solution to some of the common challenges in unifying the
      structure and process of health services across multiple small facilities, while
      meeting European prison health and local quality standards.
      DESIGN/METHODOLOGY/APPROACH: Geneva's post-trial prisons are small and close to
      one another in geographical proximity - ideal conditions for the construction of
      a health mobile team (HMT). This multidisciplinary mobile team operated like a
      community ambulatory care model; it was progressively launched in all prison
      facilities in Geneva. The authors incorporated an implementation strategy where
      health providers partnered with prison and community stakeholders in the health
      delivery model's development and adaption process. FINDINGS: The model's
      strategic initiatives are described along the following areas, in light of other
      international prison health activity and prior care models: access to a health
      care professional, equivalence of care, patient consent, confidentiality,
      humanitarian interventions, and professional competence and independence.
      ORIGINALITY/VALUE: From the perspective of the HMT members, the authors provide
      the "lessons learned" through this experience, especially to providers who are
      working on prison health services reform and coordination improvement. The paper
      particularly stresses the importance of partnering with community health
      stakeholders and prison staff, a key component to the approach.

PMID- 25758319
TI  - The vaginal microbiome during pregnancy and the postpartum period in a European
      population.
AB  - The composition and structure of the pregnancy vaginal microbiome may influence
      susceptibility to adverse pregnancy outcomes. Studies on the pregnant vaginal
      microbiome have largely been limited to Northern American populations. Using
      MiSeq sequencing of 16S rRNA gene amplicons, we characterised the vaginal
      microbiota of a mixed British cohort of women (n = 42) who experienced
      uncomplicated term delivery and who were sampled longitudinally throughout
      pregnancy (8-12, 20-22, 28-30 and 34-36 weeks gestation) and 6 weeks postpartum.
      We show that vaginal microbiome composition dramatically changes postpartum to
      become less Lactobacillus spp. dominant with increased alpha-diversity
      irrespective of the community structure during pregnancy and independent of
      ethnicity. While the pregnancy vaginal microbiome was characteristically
      dominated by Lactobacillus spp. and low alpha-diversity, unlike Northern American
      populations, a significant number of pregnant women this British population had a
      L. jensenii-dominated microbiome characterised by low alpha-diversity. L.
      jensenii was predominantly observed in women of Asian and Caucasian ethnicity
      whereas L. gasseri was absent in samples from Black women. This study reveals new
      insights into biogeographical and ethnic effects upon the pregnancy and
      postpartum vaginal microbiome and has important implications for future studies
      exploring relationships between the vaginal microbiome, host health and pregnancy
      outcomes. 

PMID- 25758321
TI  - Developing blood borne virus services across prisons in Wales, UK.
AB  - PURPOSE: This paper aims to describe the strategies being put in place to develop
      blood borne virus (BBV) services across prisons in Wales, UK, in response to the
      recommendations for prisons within the Welsh Government's Blood Borne Viral
      Hepatitis Action Plan for Wales. DESIGN/METHODOLOGY/APPROACH: A task and finish
      group was established to ensure multidisciplinary engagement between healthcare
      and custody staff. A service improvement package was developed focusing on
      awareness raising and/or development of clinical services for prisoners, prison
      officers and prison healthcare staff. FINDINGS: Prison healthcare staff have
      undergone training in BBVs and are being supported to deliver clinical services
      to prisoners. Training has been delivered in pre/post test discussion and dried
      blood spot testing; care pathways have been established between prison and
      community specialists for treatment referrals. An e-learning module is being
      rolled out to raise awareness amongst custody staff and encourage occupational
      hepatitis B vaccination. Literature on "liver health" has been produced to be
      given to every prisoner across Wales. SOCIAL IMPLICATIONS: It is envisaged that
      BBV services will become a routine part of prison care in Wales. Data on activity
      are being collected for evaluation and it is hoped that tackling BBVs in prisons
      will help reduce rates of infection both within prisons and in the wider
      community. ORIGINALITY/VALUE: This paper describes new initiatives that have been
      established to tackle BBVs across Welsh prisons and will be relevant to any
      prison healthcare staff looking to develop similar services.

PMID- 25758322
TI  - HMG CoA reductase inhibitors (statins) for preventing acute kidney injury after
      surgical procedures requiring cardiac bypass.
AB  - BACKGROUND: Acute kidney injury (AKI) is common in patients undergoing cardiac
      surgery among whom it is associated with poor outcomes, prolonged hospital stays
      and increased mortality. Statin drugs can produce more than one effect
      independent of their lipid lowering effect, and may improve kidney injury through
      inhibition of postoperative inflammatory responses. OBJECTIVES: This review aimed
      to look at the evidence supporting the benefits of perioperative statins for AKI
      prevention in hospitalised adults after surgery who require cardiac bypass. The
      main objectives were to 1) determine whether use of statins was associated with
      preventing AKI development; 2) determine whether use of statins was associated
      with reductions in in-hospital mortality; 3) determine whether use of statins was
      associated with reduced need for RRT; and 4) determine any adverse effects
      associated with the use of statins. SEARCH METHODS: We searched the Cochrane
      Renal Group's Specialised Register to 13 January 2015 through contact with the
      Trials' Search Co-ordinator using search terms relevant to this review. SELECTION
      CRITERIA: Randomised controlled trials (RCTs) that compared administration of
      statin therapy with placebo or standard clinical care in adult patients
      undergoing surgery requiring cardiopulmonary bypass and reporting AKI, serum
      creatinine (SCr) or need for renal replacement therapy (RRT) as an outcome were
      eligible for inclusion. All forms and dosages of statins in conjunction with any
      duration of pre-operative therapy were considered for inclusion in this review.
      DATA COLLECTION AND ANALYSIS: All authors extracted data independently and
      assessments were cross-checked by a second author. Likewise, assessment of study
      risk of bias was initially conducted by one author and then by a second author to
      ensure accuracy. Disagreements were arbitrated among authors until consensus was
      reached. Authors from two of the included studies provided additional data
      surrounding post-operative SCr as well as need for RRT. Meta-analyses were used
      to assess the outcomes of AKI, SCr and mortality rate. Data for the outcomes of
      RRT and adverse effects were not pooled. Adverse effects taken into account were
      those reported by the authors of included studies. MAIN RESULTS: We included
      seven studies (662 participants) in this review. All except one study was
      assessed as being at high risk of bias. Three studies assessed atorvastatin,
      three assessed simvastatin and one investigated rosuvastatin. All studies
      collected data during the immediate perioperative period only; data collection to
      hospital discharge and postoperative biochemical data collection ranged from 24
      hours to 7 days. Overall, pre-operative statin treatment was not associated with
      a reduction in postoperative AKI, need for RRT, or mortality. Only two studies
      (195 participants) reported postoperative SCr level. In those studies, patients
      allocated to receive statins had lower postoperative SCr concentrations compared
      with those allocated to no drug treatment/placebo (MD 21.2 umol/L, 95% CI -31.1
      to -11.1). Adverse effects were adequately reported in only one study; no
      difference was found between the statin group compared to placebo. AUTHORS'
      CONCLUSIONS: Analysis of currently available data did not suggest that
      preoperative statin use is associated with decreased incidence of AKI in adults
      after surgery who required cardiac bypass. Although a significant reduction in
      SCr was seen postoperatively in people treated with statins, this result was
      driven by results from a single study, where SCr was considered as a secondary
      outcome. The results of the meta-analysis should be interpreted with caution; few
      studies were included in subgroup analyses, and significant differences in
      methodology exist among the included studies. Large high quality RCTs are
      required to establish the safety and efficacy of statins to prevent AKI after
      cardiac surgery.

PMID- 25758324
TI  - Erratum to: Understanding Change in Recycling and Littering Behavior Across a
      School Social Network.

PMID- 25758323
TI  - Transcriptome analysis of northern elephant seal (Mirounga angustirostris) muscle
      tissue provides a novel molecular resource and physiological insights.
AB  - BACKGROUND: The northern elephant seal, Mirounga angustirostris, is a valuable
      animal model of fasting adaptation and hypoxic stress tolerance. However, no
      reference sequence is currently available for this and many other marine mammal
      study systems, hindering molecular understanding of marine adaptations and unique
      physiology. RESULTS: We sequenced a transcriptome of M. angustirostris derived
      from muscle sampled during an acute stress challenge experiment to identify
      species-specific markers of stress axis activation and recovery. De novo assembly
      generated 164,966 contigs and a total of 522,699 transcripts, of which 68.70%
      were annotated using mouse, human, and domestic dog reference protein sequences.
      To reduce transcript redundancy, we removed highly similar isoforms in large gene
      families and produced a filtered assembly containing 336,657 transcripts. We
      found that a large number of annotated genes are associated with metabolic
      signaling, immune and stress responses, and muscle function. Preliminary
      differential expression analysis suggests a limited transcriptional response to
      acute stress involving alterations in metabolic and immune pathways and muscle
      tissue maintenance, potentially driven by early response transcription factors
      such as Cebpd. CONCLUSIONS: We present the first reference sequence for Mirounga
      angustirostris produced by RNA sequencing of muscle tissue and cloud-based de
      novo transcriptome assembly. We annotated 395,102 transcripts, some of which may
      be novel isoforms, and have identified thousands of genes involved in key
      physiological processes. This resource provides elephant seal-specific gene
      sequences, complementing existing metabolite and protein expression studies and
      enabling future work on molecular pathways regulating adaptations such as
      fasting, hypoxia, and environmental stress responses in marine mammals.

PMID- 25758325
TI  - Considering Community Psychology Competencies: A Love Letter to Budding Scholar
      Activists Who Wonder if They Have What It Takes.
AB  - Recently, community psychologists have re-vamped a set of 18 competencies
      considered important for how we practice community psychology. Three competencies
      are: (1) ethical, reflexive practice, (2) community inclusion and partnership,
      and (3) community education, information dissemination, and building public
      awareness. This paper will outline lessons I-a white working class woman academic
      learned about my competency development through my research collaborations, using
      the lens of affective politics. I describe three lessons, from school-based
      research sites (elementary schools serving working class students of color and
      one elite liberal arts school serving wealthy white students). The first lesson,
      from an elementary school, concerns ethical, reflective practice. I discuss
      understanding my affect as a barometer of my ability to conduct research from a
      place of solidarity. The second lesson, which centers community inclusion and
      partnership, illustrates how I learned about the importance of "before the
      beginning" conversations concerning social justice and conflict when working in
      elementary schools. The third lesson concerns community education, information
      dissemination, and building public awareness. This lesson, from a college, taught
      me that I could stand up and speak out against classism in the face of my career
      trajectory being threatened. With these lessons, I flesh out key aspects of
      community practice competencies. 

PMID- 25758326
TI  - Steinernema jeffreyense n. sp. (Rhabditida: Steinernematidae), a new
      entomopathogenic nematode from South Africa.
AB  - During a non-targeted survey for entomopathogenic nematodes in South Africa, a
      new species of Steinernema was isolated from a soil sample collected from
      underneath a guava tree, close to the shore at Jeffrey's Bay. The nematode was
      isolated by means of the insect-baiting technique using last-instar larvae of
      Galleria mellonella. It is described herein as Steinernema jeffreyense n. sp. The
      nematode can be separated from other described, closely related species in terms
      of the morphological and morphometric characteristics of the different life
      stages, and in terms of the characterization and phylogeny of DNA sequences of
      the internal transcribed spacer (ITS) rDNA of the 18S gene, and of the D2D3
      region of the 28S rDNA gene. The new species is placed molecularly in the
      arenarium-glaseri-karii-longicaudatum group characterized by the following
      morphological characters: infective third-stage juvenile with a body length of
      926 (784-1043) MUm, distance from head to excretory pore of 87 (78-107) MUm, tail
      length of 81 (50-96) MUm, with an E% of 109 (86-169), and eight evenly spaced
      ridges (i.e. nine lines) in the middle of the body. First-generation males have a
      spicule length of 88 (79-95) MUm and gubernaculum length of 57 (51-61) MUm. Male
      mucron is absent in both generations. First-generation females have an
      asymmetrical protuberance and a short, double-flapped epiptygmata, with both
      flaps directed to the front. The tail of the first-generation female is shorter
      than the anal body width, with a mucron on the dorsal tail tip, with D% = 78 (59
      99). Cross-hybridization with S. khoisanae, S. tophus and S. innovationi showed
      the new species to isolate reproductively from the others. The analyses of ITS
      rDNA and D2D3 sequence of the 18S and 28S rDNA genes support the studied nematode
      isolate to be a valid new species belonging to the 'glaseri' group (Clade V). 

PMID- 25758327
TI  - MiT family translocation renal cell carcinoma.
AB  - The MiT subfamily of transcription factors includes TFE3, TFEB, TFC, and MiTF.
      Gene fusions involving two of these transcription factors have been identified in
      renal cell carcinoma (RCC). The Xp11 translocation RCCs were first officially
      recognized in the 2004 WHO renal tumor classification, and harbor gene fusions
      involving TFE3. The t(6;11) RCCs harbor a specific Alpha-TFEB gene fusion and
      were first officially recognized in the 2013 International Society of Urologic
      Pathology (ISUP) Vancouver classification of renal neoplasia. These two subtypes
      of translocation RCC have many similarities. Both were initially described in and
      disproportionately involve young patients, though adult translocation RCC may
      overall outnumber pediatric cases. Both often have unusual and distinctive
      morphologies; the Xp11 translocation RCCs frequently have clear cells with
      papillary architecture and abundant psammomatous bodies, while the t(6;11) RCCs
      frequently have a biphasic appearance with both large and small epithelioid cells
      and nodules of basement membrane material. However, the morphology of these two
      neoplasms can overlap, with one mimicking the other. Both of these RCCs
      underexpress epithelial immunohistochemical markers like cytokeratin and
      epithelial membrane antigen (EMA) relative to most other RCCs. Unlike other RCCs,
      both frequently express the cysteine protease cathepsin k and often express
      melanocytic markers like HMB45 and Melan A. Finally, TFE3 and TFEB have
      overlapping functional activity as these two transcription factors frequently
      heterodimerize and bind to the same targets. Therefore, on the basis of clinical,
      morphologic, immunohistochemical, and genetic similarities, the 2013 ISUP
      Vancouver classification of renal neoplasia grouped these two neoplasms together
      under the heading of "MiT family translocation RCC." This review summarizes our
      current knowledge of these recently described RCCs. 

PMID- 25758328
TI  - Oxygen vacancy assisted multiferroic property of Cu doped ZnO films.
AB  - Exploring multi-functional properties in a single material is the focus for
      future material design and applications. In this work, we investigated the
      multiferroic property of Cu doped ZnO films using a combination of X-ray
      diffraction (XRD), transmission electron microscopy (TEM), X-ray absorption
      spectroscopy (XAS), classical magnetometry and electric measurements. The results
      show that the texture of Cu doped ZnO films is deteriorated with an increase in
      Cu contents, whereas the dielectric property is improved due to the introduction
      of Cu ions. The XAS result reveals that the Cu atoms occupy the substitutional Zn
      sites in the ZnO host, and thus induce local electric dipoles owing to the
      displacement of the Cu-O bond. The presence of oxygen vacancies together with Cu
      ions facilitates the movement of the ferroelectric domain boundary, and
      contributes to the ferromagnetism due to the indirect exchange between Cu atoms
      and large-sized vacancy orbitals. The Cu doped ZnO film is a feasible promising
      candidate for applications in multiferroic devices. 

PMID- 25758329
TI  - Elevated serum levels of BP180 antibodies in the first trimester of pregnancy
      precede gestational pemphigoid and remain elevated for a long time after
      remission of the disease.

PMID- 25758330
TI  - Platelet-rich plasma activates tendon-derived stem cells to promote regeneration
      of Achilles tendon rupture in rats.
AB  - This study investigates whether platelet-rich plasma (PRP) is an activator of
      tendon-derived stem cells (TDSCs) to promote regeneration of Achilles tendon post
      rupture in rats. In the in vitro study, PRGF (activated PRP) significantly
      enhanced cell DNA synthesis, improved viability and promoted proliferation, while
      facilitating cell migration and the recruitment of TDSCs. In addition, TDSCs were
      mixed with collagen and PRP to form collagen-TDSC constructs (CTC) and PRP
      collagen-TDSC constructs (PCTCs). After 3 weeks of culture in vitro, we found
      that most of the encapsulated TDSCs in the CTCs and PCTCs were still alive, while
      cells in the PCTCs showed a more aligned arrangement compared to the CTCs. In
      addition, the micro-structure of PCTC showed more obvious fibre-like tissues and
      formed a cyclic microvascular structure. The tenocyte-related genes types I and
      III collagen, Tenascin-C and Scleraxis of TDSCs in the PCTCs and CTCs were
      upregulated with time, and PCTCs showed more significance than CTCs (p < 0.05).
      After in vivo transplantation, the CTCs and PCTCs showed stimulatory effects on
      Achilles tendon healing. Moreover, the PCTCs improved the macroscopic appearance,
      histological morphology and biomechanical strength of ruptured Achilles tendon
      better than CTC. These results indicate that PRP can activate TDSCs to improve
      the quality of Achilles tendon rupture healing in the early stages. Copyright (c)
      2015 John Wiley & Sons, Ltd.

PMID- 25758331
TI  - Light-controlled endosomal escape of the novel CD133-targeting immunotoxin AC133
      saporin by photochemical internalization - A minimally invasive cancer stem cell
      targeting strategy.
AB  - The cancer stem cell (CSC) marker CD133 is an attractive target to improve
      antitumor therapy. We have used photochemical internalization (PCI) for the
      endosomal escape of the novel CD133-targeting immunotoxin AC133-saporin (PCIAC133
      saporin). PCI employs an endocytic vesicle-localizing photosensitizer, which
      generates reactive oxygen species upon light-activation causing a rupture of the
      vesicle membranes and endosomal escape of entrapped drugs. Here we show that
      AC133-saporin co-localizes with the PCI-photosensitizer TPCS2a, which upon light
      exposure induces cytosolic release of AC133-saporin. PCI of picomolar levels of
      AC133-saporin in colorectal adenocarcinoma WiDr cells blocked cell proliferation
      and induced 100% inhibition of cell viability and colony forming ability at the
      highest light doses, whereas no cytotoxicity was obtained in the absence of
      light. Efficient PCI-based CD133-targeting was in addition demonstrated in the
      stem-cell-like, triple negative breast cancer cell line MDA-MB-231 and in the
      aggressive malignant melanoma cell line FEMX-1, whereas no enhanced targeting was
      obtained in the CD133-negative breast cancer cell line MCF-7. PCIAC133-saporin
      induced mainly necrosis and a minimal apoptotic response based on assessing
      cleavage of caspase-3 and PARP, and the TUNEL assay. PCIAC133-saporin resulted in
      S phase arrest and reduced LC3-II conversion compared to control treatments.
      Notably, co-treatment with Bafilomycin A1 and PCIAC133-saporin blocked LC3-II
      conversion, indicating a termination of the autophagic flux in WiDr cells. For
      the first time, we demonstrate laser-controlled targeting of CD133 in vivo. After
      only one systemic injection of AC133-saporin and TPCS2a, a strong anti-tumor
      response was observed after PCIAC133-saporin. The present PCI-based endosomal
      escape technology represents a minimally invasive strategy for spatio-temporal,
      light-controlled targeting of CD133+ cells in localized primary tumors or
      metastasis. 

PMID- 25758333
TI  - Efficacy of extracorporeal ultrasound-guided high intensity focused ultrasound:
      An evaluation based on controlled trials in China.
AB  - PURPOSE: To evaluate the efficacy of extracorporeal ultrasound-guided high
      intensity focused ultrasound (HIFU) based upon data in controlled clinical trials
      in China. MATERIALS AND METHODS: Data in 75 controlled trials involving in 833
      cases of benign and 4559 cases of malignant diseases were re-evaluated. RESULTS:
      In uterine fibroid, ectopic pregnancy and chyluria, the efficacy of HIFU was
      similar to that of surgery or drugs. The survival rate of HIFU plus radiotherapy
      was less than that of radical surgery in operable liver cancer. In inoperable
      liver cancer, the survival benefit of HIFU was similar to that of radio
      frequency, transarterial chemoembolization or gamma-knife. In pancreatic cancer,
      HIFU and chemotherapy produced similar survival rates, and HIFU did not improve
      the effect of chemotherapy or radiotherapy. HIFU did not enhance hormone therapy
      in prostate cancer. Preoperative HIFU increased rates of complete removal and of
      survival in retroperitoneal sarcoma, and increased the response rate in breast
      cancer. The response rate agreed with the survival benefit (kappa = 0.71, p =
      0.0002). CONCLUSIONS: HIFU should be curtailed in resectable cases and be an
      alternative in inoperable cases; a combination regimen should not be recommended.
      The Response Evaluation Criteria in Solid Tumors can be applied to HIFU.

PMID- 25758332
TI  - Improved intracellular delivery of peptide- and lipid-nanoplexes by natural
      glycosides.
AB  - Targeted nanocarriers undergo endocytosis upon binding to their membrane
      receptors and are transported into cellular compartments such as late endosomes
      and lysosomes. In gene delivery the genetic material has to escape from the
      cellular compartments into the cytosol. The process of endosomal escape is one of
      the most critical steps for successful gene delivery. For this reason synthetic
      lipids with fusogenic properties such as 2-dioleoyl-sn-glycero-3
      phosphoethanolamine (DOPE) are integrated into the nanocarriers. In this study we
      show that a natural, plant derived glycoside (SO1861) from Saponaria officinalis
      L. greatly improves the efficacy of lipid based as well as non-lipid based
      targeted nanoplexes consisting of a targeted K16 peptide with a nucleic acid
      binding domain and plasmid-DNA, minicircle-DNA or small interfering RNA (siRNA).
      By confocal live cell imaging and single cell analyses, we demonstrate that
      SO1861 augments the escape of the genetic cargo out of the intracellular
      compartments into the cytosol. Co-localisation experiments with fluorescence
      labelled dextran and transferrin indicate that SO1861 induces the release of the
      genetic cargo out of endosomes and lysosomes. However, the transduction efficacy
      of a lentivirus based gene delivery system was not augmented. In order to design
      receptor-targeted nanoplexes (LPD) with improved functional properties, SO1861
      was integrated into the lipid matrix of the LPD. The SO1861 sensitized LPD (LPDS)
      were characterized by dynamic light scattering and transmission electron
      microscopy. Compared to their LPD counterparts the LPDS-nanoplexes showed a
      greatly improved gene delivery. As shown by differential scanning calorimetry
      SO1861 can be easily integrated into the lipid bilayer of glycerophospholipid
      model membranes. This underlines the great potential of SO1861 as a new
      transfection multiplier for non-viral gene delivery systems. 

PMID- 25758334
TI  - Preface: issue 29.4.

PMID- 25758335
TI  - Infantile onset Vanishing White Matter disease associated with a novel EIF2B5
      variant, remarkably long life span, severe epilepsy, and hypopituitarism.
AB  - Vanishing White Matter disease (VWM) is an inherited progressive
      leukoencephalopathy caused by mutations in the genes EIF2B1-5, which encode for
      the 5 subunits of the eukaryotic initiation factor 2B (eIF2B), a regulator of
      protein synthesis. VWM typically presents with acute neurological decline
      following febrile infections or minor head trauma, and subsequent progressive
      neurological and cognitive regression. There is a varied clinical spectrum of
      VWM, with earlier onset associated with more severe phenotypes. Brain magnetic
      resonance imaging is usually diagnostic with diffusely abnormal white matter,
      progressing over time to cystic degeneration. We are reporting on a patient with
      infantile onset VWM associated with three heterozygous missense variants in
      EIF2B5, including a novel missense variant on exon 6 of EIF2B5 (D262N), as well
      as an interstitial duplication at 7q21.12. In addition, our case is unusual
      because of a severe epilepsy course, a novel clinical finding of hypopituitarism
      manifested by hypothyroidism and adrenal insufficiency, and a prolonged life span
      with current age of survival of 4 years and 11 months.

PMID- 25758336
TI  - Epigenetic variation in the Egfr gene generates quantitative variation in a
      complex trait in ants.
AB  - Complex quantitative traits, like size and behaviour, are a pervasive feature of
      natural populations. Quantitative trait variation is the product of both genetic
      and environmental factors, yet little is known about the mechanisms through which
      their interaction generates this variation. Epigenetic processes, such as DNA
      methylation, can mediate gene-by-environment interactions during development to
      generate discrete phenotypic variation. We therefore investigated the
      developmental role of DNA methylation in generating continuous size variation of
      workers in an ant colony, a key trait associated with division of labour. Here we
      show that, in the carpenter ant Camponotus floridanus, global (genome-wide) DNA
      methylation indirectly regulates quantitative methylation of the conserved cell
      signalling gene Epidermal growth factor receptor to generate continuous size
      variation of workers. DNA methylation can therefore generate quantitative
      variation in a complex trait by quantitatively regulating the transcription of a
      gene. This mechanism, alongside genetic variation, may determine the phenotypic
      possibilities of loci for generating quantitative trait variation in natural
      populations. 

PMID- 25758337
TI  - Construction of a high-density linkage map and mapping quantitative trait loci
      for somatic embryogenesis using leaf petioles as explants in upland cotton
      (Gossypium hirsutum L.).
AB  - KEY MESSAGE: The first high-density linkage map was constructed to identify
      quantitative trait loci (QTLs) for somatic embryogenesis (SE) in cotton (
      Gossypium hirsutum L.) using leaf petioles as explants. Cotton transformation is
      highly limited by only a few regenerable genotypes and the lack of understanding
      of the genetic and molecular basis of somatic embryogenesis (SE) in cotton
      (Gossypium hirsutum L.). To construct a more saturated linkage map and further
      identify quantitative trait loci (QTLs) for SE using leaf petioles as explants, a
      high embryogenesis frequency line (W10) from the commercial Chinese cotton
      cultivar CRI24 was crossed with TM-1, a genetic standard upland cotton with no
      embryogenesis frequency. The genetic map spanned 2300.41 cM in genetic distance
      and contained 411 polymorphic simple sequence repeat (SSR) loci. Of the 411
      mapped loci, 25 were developed from unigenes identified for SE in our previous
      study. Six QTLs for SE were detected by composite interval mapping method, each
      explaining 6.88-37.07% of the phenotypic variance. Single marker analysis was
      also performed to verify the reliability of QTLs detection, and the SSR markers
      NAU3325 and DPL0209 were detected by the two methods. Further studies on the
      relatively stable and anchoring QTLs/markers for SE in an advanced population of
      W10 * TM-1 and other cross combinations with different SE abilities may shed
      light on the genetic and molecular mechanism of SE in cotton.

PMID- 25758338
TI  - Role of formic receptors in soluble urokinase receptor-induced human vascular
      smooth muscle migration.
AB  - BACKGROUND: Vascular smooth muscle cell (VSMC) migration in response to urokinase
      is dependent on binding of the urokinase molecule to the urokinase plasminogen
      receptor (uPAR) and cleavage of the receptor. The aim of this study was to
      examine the role of the soluble uPAR (suPAR) in VSMC migration. METHODS: Human
      VSMCs were cultured in vitro. Linear wound and Boyden microchemotaxis assays of
      migration were performed in the presence of suPAR. Inhibitors to G-protein
      signaling and kinase activation were used to study these pathways. Assays were
      performed for mitogen-activated protein kinase and epidermal growth factor
      receptor activation. RESULTS: suPAR induced concentration-dependent migration of
      VSMC, which was G protein-dependent and was blocked by Galphai and Gbetagamma
      inhibitors. Removal of the full uPAR molecule by incubation of the cells with a
      phospholipase did not interfere with this response. suPAR induced ERK1/2,
      p38(MAPK), and c-Jun N-terminal kinase [JNK] activation in a Galphai/Gbetagamma
      dependent manner, and interruption of these signaling pathways prevented suPAR
      mediated migration. suPAR activity was independent of plasmin activity. suPAR did
      not activate epidermal growth factor receptor. Interruption of the low affinity N
      formyl-Met-Leu-Phe receptor (FPRL1) but not high affinity N-formyl-Met-Leu-Phe
      receptor (FPR) prevented cell migration and activation in response to suPAR.
      suPAR increased matrix metalloproteinase-2 expression and activity, and this was
      dependent on the low affinity N-formyl-Met-Leu-Phe receptor (FPRL1) and ERK1/2.
      CONCLUSIONS: suPAR induces human smooth muscle cell activation and migration
      independent of the full uPAR through activation of the G protein-coupled receptor
      FPRL1, which is not linked to the plasminogen activation cascade.

PMID- 25758339
TI  - A New Rabbit Model of Pediatric Traumatic Brain Injury.
AB  - Traumatic brain injury (TBI) is a common cause of disability in childhood,
      resulting in numerous physical, behavioral, and cognitive sequelae, which can
      influence development through the lifespan. The mechanisms by which TBI
      influences normal development and maturation remain largely unknown. Pediatric
      rodent models of TBI often do not demonstrate the spectrum of motor and cognitive
      deficits seen in patients. To address this problem, we developed a New Zealand
      white rabbit model of pediatric TBI that better mimics the neurological injury
      seen after TBI in children. On postnatal Day 5-7 (P5-7), rabbits were injured by
      a controlled cortical impact (6-mm impactor tip; 5.5 m/sec, 2-mm depth, 50-msec
      duration). Rabbits from the same litter served as naive (no injury) and sham
      (craniotomy alone) controls. Functional abilities and activity levels were
      measured 1 and 5 d after injury. Maturation level was monitored daily. We
      performed cognitive tests during P14-24 and sacrificed the animals at 1, 3, 7,
      and 21 d after injury to evaluate lesion volume and microglia. TBI kits exhibited
      delayed achievement of normal developmental milestones. They also demonstrated
      significant cognitive deficits, with lower percentage of correct alternation rate
      in the T-maze (n=9-15/group; p<0.001) and less discrimination between novel and
      old objects (p<0.001). Lesion volume increased from 16% at Day 3 to 30% at Day 7
      after injury, indicating ongoing secondary injury. Activated microglia were noted
      at the injury site and also in white matter regions of the ipsilateral and
      contralateral hemispheres. The neurologic and histologic changes in this model
      are comparable to those reported clinically. Thus, this rabbit model provides a
      novel platform for evaluating neuroprotective therapies in pediatric TBI. 

PMID- 25758340
TI  - Hylleraas hydride binding energy: diatomic electron affinities.
AB  - Theoretical adiabatic electron affinities are often considered inaccurate because
      they are referenced to only a single value. Ground state electron affinities for
      all the main group elements and homonuclear diatomics were identified recently
      using the normalized binding energy of the hydrogen atom: [0.75420375(3)/2 =
      0.37710187(1) eV]. Here we revisit experimental values and extend the
      identifications to diatomics in the G2-1 set. We assign new ground state electron
      affinities: (eV) Cl2, 3.2(2); Br2, 2.87(14); CH, 2.1(2); H2, 0.6 ; NH, 1.1, SiH,
      1.90. Anion Morse potentials are calculated for H2 and N2 from positive electron
      affinities and for hyperfine superoxide states for the first time. 

PMID- 25758341
TI  - Relative stabilities of HCl*H2SO4*HNO3 aggregates in polar stratospheric clouds.
AB  - Strong acids such as HCl (C), HNO3 (N) and H2SO4 (S) acquire relevance in Polar
      Stratospheric Clouds (PSCs) and aerosols in which nucleation processes occur. Ab
      initio quantum chemical studies of aggregates were performed for these strong
      acids. Structures were calculated using DFT methods with the B3LYP hybrid
      functional and aug-cc-pVTZ basis set. As an initial constraint, an H2SO4 moiety
      was placed in all candidate structures. A total of 11 optimized structures was
      found: a global minimum (CSN-a) plus ten local minima on the Potential Energy
      Surface (PES). The global minimum aggregate gave four hydrogen bonds, yielding a
      hexagonal ring in its structure. HNO3 acts as proton donor in all clusters;
      nevertheless, using trans-H2SO4 as the proton donor yielded the most stable
      structures, whereas HCl acts mainly as a proton donor/acceptor. Real harmonic
      frequencies, IR spectra, and inter-monomeric parameters were obtained. CSN-a
      symmetric stretching modes were shifted to 2805.56 cm(-1) and 3520.00 cm(-1) for
      H-Cl modes, while O-H modes shifted to 3256.87 cm(-1) and 3362.47 cm(-1). On the
      other hand, relative stabilities improved for 5 of the 11 aggregates when the
      temperature decreased from 298 K to 210 K, 195 K and 188 K. The aggregate CSN-f
      remained unstable only at 210 K. Moreover, the relative Gibbs free energy,
      DeltaG(0-298K) was -9.26 kcalmol(-1) with respect to CSN-a; relative reaction
      Gibbs free energy [Delta(DeltaG)] values ranged from 0.0 at 298 K, to -6.9
      kcalmol(-1) at 188 K. It seems that CSN aggregates remain slightly more stable
      than CNS aggregates with a HNO3 moiety when the temperature decreases from 298 to
      188 K. Five structures remained relatively stable under both study conditions.

PMID- 25758342
TI  - The N2O activation by Rh5 clusters. A quantum chemistry study.
AB  - Nitrous oxide (N2O) is a by-product of exhaust pipe gases treatment produced by
      motor vehicles. Therefore, the N2O reduction to N2 is necessary to meet the
      actual environmental legislation. The N2O adsorption and dissociation assisted by
      the square-based pyramidal Rh5 cluster was investigated using the density
      functional theory and the zero-order regular approximation (ZORA). The Rh5 sextet
      ground state is the most active in N2O dissociation, though the quartet and octet
      states are also active because they are degenerate. The Rh5 cluster spontaneously
      activates the N2?O cleavage, and the reaction is highly exothermic ca. -75 kcal
      mol(-1). The N2?O breaking is obtained for the geometrical arrangement that
      maximizes the overlap and electron transfers between the N2O and Rh5 frontier
      orbitals. The Rh5 high activity is due to the Rh 3d orbitals are located between
      the N2O HOMO and LUMO orbitals, which makes possible the interactions between
      them. In particular, the O 2p states strongly interact with Rh 3d orbitals, which
      finally weaken the N2?O bond. The electron transfer is from the Rh5 HOMO orbital
      to the N2O antibonding orbital. 

PMID- 25758343
TI  - Pituitary adenylate cyclase-activating polypeptide deficiency associated with
      increased platelet count and aggregability in nephrotic syndrome.
AB  - BACKGROUND: Pituitary adenylate cyclase-activating polypeptide (PACAP) was
      recently identified as an inhibitor of megakaryopoiesis and platelet
      aggregability. OBJECTIVE: We studied PACAP levels in children with nephrotic
      syndrome (NS), which is associated with thrombocytosis, platelet
      hyperaggregability, and an increased risk of thrombosis. PATIENTS/METHODS: In
      four children with congenital NS (CNS) and 24 children with idiopathic NS (INS),
      plasma and urine levels of PACAP and ceruloplasmin were measured, as were
      platelet counts and platelet aggregation responses to collagen. In CNS patients,
      in vitro megakaryopoiesis and nuclear factor-kappaB expression in platelet
      lysates were also measured. All tests were performed during the nephrotic state
      and the non-nephrotic state. RESULTS: Urinary losses of PACAP and ceruloplasmin
      were observed during the nephrotic state, and disappeared during the non
      nephrotic state. Plasma PACAP deficiency was more pronounced in CNS patients than
      in INS patients. Thrombocytosis was observed in all CNS patients and in 11 of 29
      INS patients during the nephrotic state. During the PACAP-deficient state, in
      vitro megakaryopoiesis was increased for CNS patients, and this effect could be
      reversed by the addition of recombinant PACAP. Platelet hyperaggregability was
      observed during the nephrotic state in both CNS and INS patients. In INS
      patients, the addition of recombinant PACAP to patients' platelets was studied,
      and resulted in decreased aggregation during the nephrotic state. Platelet
      aggregation correlated inversely with plasma PACAP levels, but not with serum
      albumin levels. CONCLUSIONS: We demonstrate urinary losses of PACAP and plasma
      PACAP deficiency in children with NS, associated with thrombocytosis and platelet
      hyperaggregability.

PMID- 25758344
TI  - Non-invasive diagnosis of sweat gland dysplasia using optical coherence
      tomography and reflectance confocal microscopy in a family with anhidrotic
      ectodermal dysplasia (Christ-Siemens-Touraine syndrome).
AB  - BACKGROUND: Anhidrotic ectodermal dysplasia (AED) is an inherited syndrome, which
      originates mainly from genetic alteration of the ectodysplasin A (EDA) gene. It
      regularly affects the adnexa of the skin which results in a characteristic
      phenotype of the patients including hypo- or anhidrosis leading to severe
      disturbances in the regulation of body temperature. OBJECTIVES: To prevent the
      development of the symptoms in early childhood promising therapeutic approaches
      are currently under clinical investigation. In this context, timely diagnosis of
      this genetic syndrome is crucial. The purpose of our study was the investigation
      of modern non-invasive imaging methods such as optical coherence tomography (OCT)
      and reflectance confocal microscopy (RCM) in the immediate diagnosis of AED.
      METHODS: We examined a 3-year-old boy with the suspicion for an AED syndrome and
      his family members with RCM and OCT to document presence and characteristic
      features of sweat glands in comparison to non-affected individuals. RESULTS: The
      patient and the affected brother showed significantly reduced sweat glands in the
      imaging compared to the controls. The genetic analysis revealed a mutation of the
      EDA gene for hemizygosity previously associated with AED and the mother was
      revealed as the conductor of the genetic alteration. CONCLUSIONS: With the help
      of non-invasive imaging, we were able to detect sweat gland dysplasia in the
      affected family members without performing a biopsy which led us to the diagnosis
      of an AED. The application of modern dermatological imaging techniques might
      serve as valuable supplementary tools in the immediate, non-invasive diagnosis of
      genetic syndromes especially in newborns when early therapeutic approaches are
      planned.

PMID- 25758346
TI  - Comparison of modified limberg flap and modified elliptical rotation flap for
      pilonidal sinus surgery: a retrospective cohort study.
AB  - BACKGROUND: Although various surgical procedures have been described for
      pilonidal sinus disease, the best surgical technique is still controversial. Aim
      of this study was to compare the short term results of modified limberg flap
      (MLF) and modified elliptical rotation flap (MERF) for pilonidal sinus disease in
      terms of postoperative complications, recurrence and patient satisfaction.
      MATERIALS AND METHOD: Two hundred and thirty six patients (43 female, 193 male)
      who were operated on for sacrococcygeal pilonidal sinus disease between January
      2010 to December 2013 were retrospectively analyzed. 115 patients underwent
      Modified limberg flap (MLF) procedure and 121 patients underwent modified
      elliptical rotation flap (MERF) procedure. The median follow-up period was 22
      months (range, 4-34). Complication and recurrence rate were the mean end points
      of the study. RESULTS: Surgical area related complications were lower in MERF
      group than in MLF group, but the difference was not statistically significant.
      Patients in the modified elliptical rotation flap group had shorter operation
      time, better cosmetic results and earlier return to normal social life than
      modified limberg flap group. There were no recurrences in MERF group but one
      recurrence in MLF group. CONCLUSION: Modified limberg flap reconstruction is
      still one of the most commonly performed procedures for pilonidal sinus disease
      because of its low complication and recurrence rate and higher postoperative
      quality of life. This study shows that modified elliptical rotation flap
      technique is at least effective as modified limberg flap reconstruction. Further
      prospective clinical trials are needed to show the effectiveness of this
      technique on long term.

PMID- 25758345
TI  - Artificial human Met agonists based on macrocycle scaffolds.
AB  - Hepatocyte growth factor (HGF) receptor, also known as Met, is a member of the
      receptor tyrosine kinase family. The Met-HGF interaction regulates various
      signalling pathways involving downstream kinases, such as Akt and Erk. Met
      activation is implicated in wound healing of tissues via multiple biological
      responses triggered by the above-mentioned signalling cascade. Here we report the
      development of artificial Met-activating dimeric macrocycles. We identify Met
      binding monomeric macrocyclic peptides by means of the RaPID (random non-standard
      peptide integrated discovery) system, and dimerize the respective monomers
      through rational design. These dimeric macrocycles specifically and strongly
      activate Met signalling pathways through receptor dimerization and induce various
      HGF-like cellular responses, such as branching morphogenesis, in human cells.
      This work suggests our approach for generating dimeric macrocycles as non-protein
      ligands for cell surface receptors can be useful for developing potential
      therapeutics with a broad range of potential applications. 

PMID- 25758347
TI  - An observational study investigating the effect of platelet function on outcome
      after colorectal surgery.
AB  - INTRODUCTION: Previous studies have assumed patients have uniform responses to
      aspirin, yet significant numbers are occult hypo- or hyper-responders. A new
      validated test of platelet function measures platelet P-selectin expression,
      which rises with increased platelet activity. This study investigated the
      measured perioperative changes in platelet function in response to aspirin, and
      subsequently whether quantitative variations in platelet activity affected
      perioperative complication severity and frequency. METHODS: 107 patients
      undergoing major colorectal surgery were recruited and assigned to either control
      (no antiplatelet therapy) or aspirin groups. P-selectin was measured following
      platelet stimulation at recruitment prior to cessation of medication, and at
      surgery before intervention. Perioperative complications, hemoglobin changes and
      blood transfusions were also recorded. RESULTS: Platelet function was higher in
      control (n = 87) than aspirin group (n = 20) at recruitment (median 1303u [IQR
      1102-1499] vs 77u [IQR 63.5-113.5],P < 0.01) and surgery (median 1224u [IQR 944
      1496] vs 281.5u [IQR 106.8-943], P < 0.01). There was a positive correlation
      between length of aspirin cessation and platelet function at surgery (R(S) =
      0.66, P < 0.01). Complication rates and hemorrhagic complication rates (P < 0.05)
      were higher with aspirin than control, although complication severity was not
      increased. Platelet function of the entire cohort at surgery was not associated
      with complication rate, severity or transfusion use. DISCUSSION: Although
      complication rates were higher in aspirin group, impaired platelet function
      within ranges seen with aspirin continuation did not affect complication severity
      or rate or blood transfusion use. Consequently, aspirin continuation may not
      affect clinical outcome in patients undergoing major colorectal surgery and
      requires further investigation with a large randomized trial.

PMID- 25758348
TI  - Current status of minimally invasive surgery for gastric cancer: A literature
      review to highlight studies limits.
AB  - BACKGROUND: Gastric cancer represents a great challenge for health care providers
      and requires a multidisciplinary approach in which surgery plays the main role.
      Minimally invasive surgery has been progressively developed, first with the
      advent of laparoscopy and more recently with the spread of robotic surgery, but a
      number of issues are currently being investigate, including the limitations in
      performing effective extended lymph node dissections and, in this context, the
      real advantages of using robotic systems, the possible role for advanced Gastric
      Cancer, the reproducibility of completely intracorporeal techniques and the
      oncological results achievable during follow-up. METHOD: Searches of MEDLINE,
      Embase and Cochrane Central Register of Controlled Trials were performed to
      identify articles published until April 2014 which reported outcomes of surgical
      treatment for gastric cancer and that used minimally invasive surgical
      technology. Articles that deal with endoscopic technology were excluded. RESULTS:
      A total of 362 articles were evaluated. After the review process, data in 115
      articles were analyzed. CONCLUSION: A multicenter study with a large number of
      patients is now needed to further investigate the safety and efficacy as well as
      long-term outcomes of robotic surgery, traditional laparoscopy and the open
      approach.

PMID- 25758349
TI  - Correlation of breaking forces, conductances and geometries of molecular
      junctions.
AB  - Electrical and mechanical properties of elongated gold-molecule-gold junctions
      formed by tolane-type molecules with different anchoring groups (pyridyl, thiol,
      amine, nitrile and dihydrobenzothiophene) were studied in current-sensing force
      spectroscopy experiments and density functional simulations. Correlations between
      forces, conductances and junction geometries demonstrate that aromatic tolanes
      bind between electrodes as single molecules or as weakly-conductive dimers held
      by mechanically-weak pi - pi stacking. In contrast with the other anchors that
      form only S-Au or N-Au bonds, the pyridyl ring also forms a highly-conductive
      cofacial link to the gold surface. Binding of multiple molecules creates
      junctions with higher conductances and mechanical strengths than the single
      molecule ones. 

PMID- 25758351
TI  - Ligand-functionalized degradable polyplexes formed by cationic poly(aspartic
      acid)-grafted chitosan-cyclodextrin conjugates.
AB  - Polypeptide-based degradable polyplexes attracted considerable attention in drug
      delivery systems. Polysaccharides including cyclodextrin (CD), dextran, and
      chitosan (CS) were readily grafted with cationic poly(aspartic acid)s (PAsps). To
      further enhance the transfection performances of PAsp-based polyplexes, herein,
      different types of ligand (folic acid, FA)-functionalized degradable polyplexes
      were proposed based on the PAsp-grafted chitosan-cyclodextrin conjugate (CCPE),
      where multiple beta-CDs were tied on a CS chain. The FA-functionalized CCPE
      (i.e., CCPE-FA) was obtained via a host-guest interaction between the CD units of
      CCPE and the adamantane (Ad) species of Ad-modified FA (Ad-FA). The resulting
      CCPE/pDNA, CCPE-FA/pDNA, and ternary CCPE-FA/CCPE/pDNA (prepared by layer-by
      layer assembly) polyplexes were investigated in detail using different cell
      lines. The CCPE-based polyplexes displayed much higher transfection efficiencies
      than the CS-based polyplexes reported earlier by us. The ternary polyplexes of
      CCPE-FA/CCPE/pDNA produced excellent gene transfection abilities in the folate
      receptor (FR)-positive tumor cells. This work would provide a promising means to
      produce highly efficient polyplexes for future gene therapy applications. 

PMID- 25758350
TI  - Reconstruction of cyclooxygenase evolution in animals suggests variable, lineage
      specific duplications, and homologs with low sequence identity.
AB  - Cyclooxygenase (COX) enzymatically converts arachidonic acid into prostaglandin
      G/H in animals and has importance during pregnancy, digestion, and other
      physiological functions in mammals. COX genes have mainly been described from
      vertebrates, where gene duplications are common, but few studies have examined
      COX in invertebrates. Given the increasing ease in generating genomic data, as
      well as recent, although incomplete descriptions of potential COX sequences in
      Mollusca, Crustacea, and Insecta, assessing COX evolution across Metazoa is now
      possible. Here, we recover 40 putative COX orthologs by searching publicly
      available genomic resources as well as ~250 novel invertebrate transcriptomic
      datasets. Results suggest the common ancestor of Cnidaria and Bilateria possessed
      a COX homolog similar to those of vertebrates, although such homologs were not
      found in poriferan and ctenophore genomes. COX was found in most crustaceans and
      the majority of molluscs examined, but only specific taxa/lineages within
      Cnidaria and Annelida. For example, all octocorallians appear to have COX, while
      no COX homologs were found in hexacorallian datasets. Most species examined had a
      single homolog, although species-specific COX duplications were found in members
      of Annelida, Mollusca, and Cnidaria. Additionally, COX genes were not found in
      Hemichordata, Echinodermata, or Platyhelminthes, and the few previously described
      COX genes in Insecta lacked appreciable sequence homology (although structural
      analyses suggest these may still be functional COX enzymes). This analysis
      provides a benchmark for identifying COX homologs in future genomic and
      transcriptomic datasets, and identifies lineages for future studies of COX. 

PMID- 25758352
TI  - International Guidelines for Bioequivalence of Locally Acting Orally Inhaled Drug
      Products: Similarities and Differences.
AB  - International regulatory agencies have developed recommendations and guidances
      for bioequivalence approaches of orally inhaled drug products (OIDPs) for local
      action. The objective of this article is to discuss the similarities and
      differences among these approaches used by international regulatory authorities
      when applications of generic and/or subsequent entry locally acting OIDPs are
      evaluated. We focused on four jurisdictions that currently have published related
      guidances for generic and/or subsequent entry OIDPs. They are Therapeutic Goods
      Administration (TGA) in Australia, Health Canada (HC) in Canada, European
      Medicines Association (EMA) of European Union (EU), and the Food and Drug
      Administration (FDA) in the United States of America (USA). The comparisons of
      these bioequivalence (BE) recommendations are based on selection of reference
      products, formulation and inhaler device comparisons, and in vitro tests and in
      vivo studies, including pharmacokinetic (PK), pharmacodynamics (PD), and clinical
      studies. For the in vivo studies, the study design, choices of dose, subject
      inclusion/ exclusion criteria, study period, study endpoint, and equivalence
      criteria are elaborated in details. The bioequivalence on multiple-strength
      products and waiver options are also discussed. 

PMID- 25758353
TI  - How to predict and treat increased fracture risk in chronic kidney disease.
AB  - Men and women with chronic kidney disease (CKD) are at an increased risk of
      fracture, and this risk increases as kidney function deteriorates. Fractures are
      associated with morbidity, mortality and economic costs. Despite this, there is a
      paucity of data regarding how to evaluate risk for fractures in CKD and how to
      treat high-risk patients. Evidence suggests that bone mineral density (BMD) as
      assessed by dual-energy X-ray absorptiometry (DXA) is associated with fractures
      and can also predict future fractures in predialysis (stages 1-3) patients with
      CKD. In the absence of considerable abnormalities in markers of mineral
      metabolism, treatment with antiresorptive agents in men and women with early CKD
      at high fracture risk may be appropriate. Of note, recent data suggest that low
      BMD as measured by DXA can also predict fractures in patients with more advanced
      CKD (stages 4, 5 and 5D). However, treatment in patients with advanced CKD
      requires bone biopsy, the gold standard to assess bone turnover, prior to
      treatment. Further research, focusing on noninvasive methods to assess fracture
      risk and bone turnover, together with randomized controlled trials of treatments
      to reduce fractures in patients at all stages of CKD, is required.

PMID- 25758354
TI  - Antioxidant capacity and structural changes of human serum albumin from patients
      in advanced stages of diabetic nephropathy and the effect of the dialysis.
AB  - Changes in the antioxidant capacity of albumin and alterations of the albumin
      structural conformation were examined in patients in advanced stages of diabetes
      nephropathy. Human serum albumin was purified from diabetic patients in pre
      dialysis (glomerular filtration rate [GFR] between 15 and 29 ml min(-1) 1.73 m(
      2)) and those in dialysis (GFR <= 15 ml min(-1) 1.73 m(-2)) and then compared
      with albumin from patients with a normal GFR (>90 ml min(-1) m(-2)). We evaluated
      the antioxidant capacity of albumin using an enhanced chemiluminescence-based
      assay and thiol group content, and the structural changes were evaluated by
      circular dichroism and fluorescence spectroscopy. The antioxidant capacity and
      thiol content of albumin from patients in advanced stages of diabetic nephropathy
      were markedly reduced. The circular dichroism spectra showed a mean albumin alpha
      helix content reduction from 44 to 37 % and from 44 to 30 % between the control
      group and pre-dialysis and dialysis patients, respectively. Additionally, the
      fluorescence intensity was reduced by 4.2 and 13 % for the groups 4 and 5,
      respectively, in relation with the control. These data provide evidence for the
      partial denaturation of albumin and exacerbated oxidative stress among patients
      in advanced stages of diabetes nephropathy before and even after dialysis.

PMID- 25758355
TI  - Na(+)/H (+) exchanger isoform 1 induced osteopontin expression in cardiomyocytes
      involves NFAT3/Gata4.
AB  - Osteopontin (OPN), a multifunctional glycophosphoprotein, has been reported to
      contribute to the development and progression of cardiac remodeling and
      hypertrophy. Cardiac-specific OPN knockout mice were protected against
      hypertrophy and fibrosis mediated by Ang II. Recently, transgenic mice expressing
      the active form of the Na(+)/H(+) exchanger isoform 1 (NHE1) developed
      spontaneous hypertrophy in association with elevated levels of OPN. The mechanism
      by which active NHE1 induces OPN expression and contributes to the hypertrophic
      response remains unclear. To validate whether expression of the active form of
      NHE1 induces OPN, cardiomyocytes were stimulated with Ang II, a known inducer of
      both OPN and NHE1. Ang II induced hypertrophy and increased OPN protein
      expression (151.6 +/- 28.19 %, P < 0.01) and NHE1 activity in H9c2
      cardiomyoblasts. Ang II-induced hypertrophy and OPN protein expression were
      regressed in the presence of an NHE1 inhibitor, EMD 87580, or a calcineurin
      inhibitor, FK506. In addition, our results indicated that activation of NHE1
      induced NFAT3 translocation into the nucleus and a significant activation of the
      transcription factor Gata4 (NHE1: 149 +/- 28 % of control, P < 0.05). NHE1
      induced activation of Gata4 was inhibited by FK506. In summary, our results
      suggest that activation of NHE1 induces hypertrophy through the activation of
      NFAT3/Gata4 and OPN expression.

PMID- 25758356
TI  - Rac1 GTPase-deficient HeLa cells present reduced DNA repair, proliferation, and
      survival under UV or gamma irradiation.
AB  - Rac1 GTPase controls essential cellular functions related to the cytoskeleton,
      such as motility and adhesion. Rac1 is overexpressed in many tumor cells,
      including breast cancers, where it is also involved in the proliferation and
      checkpoint control necessary for the cell's recovery after exposure to ionizing
      radiation. However, its role in DNA damage and repair remains obscure in other
      tumor cells and under different genotoxic conditions. Here, we compare HeLa cells
      with mutants exogenously expressing a dominant-negative Rac1 (HeLa-Rac1-N17) by
      their responses to DNA damage induced by gamma or UV radiation. In HeLa cells,
      these treatments led to increased levels of active Rac1 (Rac1-GTP) and of stress
      fibers, with a diminished ability to migrate compared to untreated cells.
      However, the reduction of Rac1-GTP in Rac1-N17-deficient clones resulted in much
      higher levels of polymerized stress fibers accompanied by a strong impairment of
      cell migration, even after both radiation treatments. With regard to
      proliferation and genomic stability, dominant-negative Rac1 cells were more
      sensitive to gamma and UV radiation, exhibiting reduced proliferation and
      survival consistent with increased DNA damage and delayed or reduced DNA repair
      observed in this Rac1-deficient clone. The DNA damage response, as indicated by
      pH2AX and pChk1 levels, was increased in HeLa cells but was not effectively
      triggered in the Rac1-N17 clone after radiation treatment, which is likely the
      main cause of DNA damage accumulation. These data suggest that Rac1 GTPase plays
      an important role in signaling and contributes to the sensitivity of cervical
      cancer cells under UV or gamma radiation treatments. 

PMID- 25758357
TI  - Improving resistance to the European corn borer: a comprehensive study in elite
      maize using QTL mapping and genome-wide prediction.
AB  - KEY MESSAGE: The efficiency of marker-assisted selection for native resistance to
      European corn borer stalk damage can be increased when progressing from a QTL
      based towards a genome-wide approach. Marker-assisted selection (MAS) has been
      shown to be effective in improving resistance to the European corn borer (ECB) in
      maize. In this study, we investigated the performance of whole-genome-based
      selection, relative to selection based on individual quantitative trait loci
      (QTL), for resistance to ECB stalk damage in European elite maize. Three
      connected biparental populations, comprising 590 doubled haploid (DH) lines, were
      genotyped with high-density single nucleotide polymorphism markers and phenotyped
      under artificial and natural infestation in 2011. A subset of 195 DH lines was
      evaluated in the following year as lines per se and as testcrosses. Resistance
      was evaluated based on stalk damage ratings, the number of feeding tunnels in the
      stalk and tunnel length. We performed individual- and joint-population QTL
      analyses and compared the cross-validated predictive abilities of the QTL models
      with genomic best linear unbiased prediction (GBLUP). For all traits, the GBLUP
      model consistently outperformed the QTL model despite the detection of QTL with
      sizeable effects. For stalk damage rating, GBLUP's predictive ability exceeded at
      times 0.70. Model training based on DH line per se performance was efficient in
      predicting stalk breakage in testcrosses. We conclude that the efficiency of MAS
      for ECB stalk damage resistance can be increased considerably when progressing
      from a QTL-based towards a genome-wide approach. With the availability of native
      ECB resistance in elite European maize germplasm, our results open up avenues for
      the implementation of an integrated genome-based selection approach for the
      simultaneous improvement of yield, maturity and ECB resistance.

PMID- 25758358
TI  - The Clinical Effectiveness of the Extended-Scope Physiotherapist Role in
      Musculoskeletal Triage: A Systematic Review.
AB  - BACKGROUND: Extended-scope physiotherapists (ESPs) are working in musculoskeletal
      (MSK) triage clinics to assess, diagnose and refer patients for appropriate
      management. However, there is inadequate appraisal of their clinical
      effectiveness. OBJECTIVES: The aim of the present systematic review was to
      appraise the evidence on the diagnostic ability of ESPs in MSK triage, and
      patient and general practitioner (GP) satisfaction when seen by an ESP in a MSK
      clinic. METHOD: CINAHL, AMED, MEDLINE and EMBASE databases were searched from
      1989 to February 2014 using the keywords 'physiotherapy', 'extended practitioner'
      and 'musculoskeletal disease'. Data extraction was compiled using the Centre for
      Reviews and Dissemination (2009) method. Diagnostic accuracy studies were
      assessed for methodological quality using the Scottish Intercollegiate Guideline
      Network (SIGN). Patient/GP satisfaction was assessed using a tool adapted by
      Desmeules et al. (2012). RESULTS: From 146 studies initially identified, 14 were
      eligible for review. Only one diagnostic study was of high quality, and
      satisfaction study scores ranged from 40% to 73%. All studies reported favourable
      outcomes for ESPs in MSK triage clinics, with ESPs demonstrating a good level of
      diagnostic ability in comparison with a gold standard such as surgery. In
      addition, patients and GPs were satisfied with the overall performance and
      service provided by ESPs. CONCLUSION: The evidence suggests that ESPs are
      clinically effective. However, there were methodological shortcomings in the
      reviewed studies, and further research, using larger sample sizes, multiple
      locations and comparisons of the same patient cohorts, would strengthen the
      evidence available to influence future commissioning of these services. Copyright
      (c) 2015 John Wiley & Sons, Ltd.

PMID- 25758359
TI  - Cardiac amyloidosis: the great pretender.
AB  - Cardiac amyloidosis (CA) is often misdiagnosed because of both physician-related
      and disease-related reasons including: fragmented knowledge among different
      specialties and subspecialties, shortage of centres and specialists dedicated to
      disease management, erroneous belief it is an incurable disease, rarity of the
      condition, intrinsic phenotypic heterogeneity, genotypic heterogeneity in
      transthyretin-related forms and the necessity of target organ tissue histological
      diagnosis in the vast majority of cases. Pitfalls, incorrect beliefs and deceits
      challenge not only the path to the diagnosis of CA but also the precise
      identification of aetiological subtype. The awareness of this condition is the
      most important prerequisite for the management of the risk of underdiagnoses and
      misdiagnosis. Almost all clinical, imaging and laboratory tests can be
      misinterpreted, but fortunately each of these diagnostic steps can also offer
      diagnostic "red flags" (i.e. highly suggestive findings that can foster the
      correct diagnostic suspicion and facilitate early, timely diagnosis). This is
      especially important because outcomes in CA are largely driven by the severity of
      cardiac dysfunction and emerging therapies are aimed at preventing further
      amyloid deposition. 

PMID- 25758360
TI  - Saving more teeth-a case for personalized care.
AB  - BACKGROUND: Certain risk factors such as tobacco use, diabetes, genetic
      variations on the IL1 gene, and other inflammatory conditions are hypothesized to
      predict tooth loss in patients treated in a large medical center. Tooth loss
      trends are hypothesized to be greater in patients with more risk factors.
      METHODS: DNA samples for 881 individuals were taken from the Dental Registry and
      DNA Repository at University of Pittsburgh School of Dental Medicine. Clinical
      data for all 4137 subjects in the registry were also available. SNP genotyping
      was performed on the samples for IL1alpha (rs1800587) and IL1beta (rs1143634).
      IL1 positive status was determined as having one or more of the recessive alleles
      for either SNP. Tooth loss status was determined based on dental records and data
      gathered for age, sex, ethnicity, and self-reported medical history. Various
      statistical analyses were performed on the data including genetic association
      analysis by the PLINK software, chi-square, Mann-Whitney U, and ANOVA tests to
      determine significance. RESULTS: Tooth loss averages increased with age by all
      risk factors (smoking, diabetes, hypertension, and interleukin genotypes; p =
      4.07E-13) and by number of risk factors (p = 0.006). Increased tooth loss is
      associated with age and number of risk factors including diabetes, tobacco use,
      IL1+, and cardiovascular disease. CONCLUSION: These trends suggest that older
      patients and those with more risk factors should seek further preventive care to
      reduce future tooth loss.

PMID- 25758361
TI  - Glycosaminoglycan chemical exchange saturation transfer of lumbar intervertebral
      discs in patients with spondyloarthritis.
AB  - PURPOSE: To assess glycosaminoglycan (GAG) content of lumbar intervertebral discs
      (IVD) in patients with spondyloarthritis (SpA) using glycosaminoglycan chemical
      exchange saturation transfer (gagCEST). MATERIALS AND METHODS: Ninety lumbar
      intervertebral discs of nine patients with SpA and nine age-matched healthy
      controls (eight patients with ankylosing spondylitis; one patient with
      spondylitis related to inflammatory bowel disease; mean age: 44.1 +/- 14.0 years;
      range: 27-72 years) were examined with a 3T magnetic resonance imaging (MRI)
      scanner in this prospective study. The MRI protocol included standard
      morphological, sagittal T2 -weighted (T2 w) images to assess Pfirrmann score of
      the five lumbar IVDs (L1 to S1) and biochemical imaging with gagCEST to calculate
      a region of interest analysis of nucleus pulposus (NP) and annulus fibrosus (AF).
      Prior to statistical testing of gagCEST effects (MTRasym values in percent) in
      patients and controls, IVDs were classified according to the Pfirrmann score.
      RESULTS: Significantly lower gagCEST values of NP and AF were found in SpA
      patients compared with healthy volunteers (NP: 1.41% +/- 0.41%, P = 0.001; 95%
      confidence interval, CI [0.600%-2.226%]; AF: 1.19% +/- 0.32%, P < 0.001; CI
      [0.560%-1.822%]) by comparing the differences of the means. Pooled
      nondegenerative IVDs (Pfirrmann 1 and 2) had significantly lower gagCEST effects
      in patients suffering from SpA compared with healthy controls in NP (P < 0.001;
      CI [1.176%-2.337%]) and AF (P < 0.001; CI [0.858%-1.779%]). No significant
      difference of MTRasym values was found in degenerative IVDs between patients and
      controls in NP (P = 0.204; CI [-0.504%-2.170%]). CONCLUSION: GagCEST analysis of
      morphologically nondegenerative IVDs (Pfirrmann score 1 and 2) in T2 w images
      demonstrated significantly lower GAG values in patients with spondyloarthritis in
      NP and AF, possibly representing a depletion of GAG in spondyloarthritis in the
      absence of morphologic degeneration.

PMID- 25758362
TI  - Permutation testing in the presence of polygenic variation.
AB  - This article discusses problems with and solutions to performing valid
      permutation tests for quantitative trait loci in the presence of polygenic
      effects. Although permutation testing is a popular approach for determining
      statistical significance of a test statistic with an unknown distribution--for
      instance, the maximum of multiple correlated statistics or some omnibus test
      statistic for a gene, gene-set, or pathway--naive application of permutations may
      result in an invalid test. The risk of performing an invalid permutation test is
      particularly acute in complex trait mapping where polygenicity may combine with a
      structured population resulting from the presence of families, cryptic
      relatedness, admixture, or population stratification. I give both analytical
      derivations and a conceptual understanding of why typical permutation procedures
      fail and suggest an alternative permutation-based algorithm, MVNpermute, that
      succeeds. In particular, I examine the case where a linear mixed model is used to
      analyze a quantitative trait and show that both phenotype and genotype
      permutations may result in an invalid permutation test. I provide a formula that
      predicts the amount of inflation of the type 1 error rate depending on the degree
      of misspecification of the covariance structure of the polygenic effect and the
      heritability of the trait. I validate this formula by doing simulations, showing
      that the permutation distribution matches the theoretical expectation, and that
      my suggested permutation-based test obtains the correct null distribution.
      Finally, I discuss situations where naive permutations of the phenotype or
      genotype are valid and the applicability of the results to other test statistics.

PMID- 25758363
TI  - The relationship of psychological trauma and dissociative and posttraumatic
      stress disorders to nonsuicidal self-injury and suicidality: a review.
AB  - We reviewed research on the relationship between (a) exposure to psychological
      trauma and (b) nonsuicidal self-injury (NSSI) and suicidality (suicidal ideation
      [SI] and suicide attempts [SA]) in individuals with dissociative disorders and
      posttraumatic stress disorder (PTSD). The review provides a context for the
      special issue of the Journal of Trauma & Dissociation on these topics. Exposure
      to childhood sexual abuse is the most consistent traumatic antecedent of self
      harm, although traumatic violence in childhood (particularly physical abuse) and
      adulthood (particularly domestic violence) and exposure to multiple types of
      traumatic stressors also are associated with NSSI and SI/SA. Dissociative
      disorders and PTSD are consistently associated with increased NSSI and SA/SI.
      There is preliminary cross-sectional evidence that dissociation and posttraumatic
      stress disorders may mediate the relationship between psychological trauma and
      NSSI and SI/SA. Research on emotion dysregulation as a potential cross-cutting
      mechanism linking dissociation, PTSD, and self-harm is also reviewed. We conclude
      with a discussion of implications for clinical practice and future directions for
      scientific research. 

PMID- 25758364
TI  - Substantia nigra neuromelanin-MR imaging differentiates essential tremor from
      Parkinson's disease.
AB  - BACKGROUND: Essential tremor (ET) is a very common movement disorder that has no
      diagnostic markers. Differentiation with Parkinson's disease (PD) can be
      clinically challenging in some cases, with a high rate of misdiagnosis. Magnetic
      resonance imaging (MRI) studies have been able to identify neuromelanin changes
      in the substantia nigra (SN) of PD patients, but they have thus far not been
      investigated in ET. In this study, we aimed to characterize neuromelanin-MR
      signal changes in ET and evaluate its diagnostic accuracy in the differential
      diagnosis with PD. METHODS: The inclusion criteria were patients with ET and
      untreated "de novo" PD patients; in addition, age-matched controls were enrolled.
      These were studied with a high-resolution T1-weighted MRI sequence at 3.0 Tesla
      to visualize neuromelanin. The primary outcomes were the area and width of the SN
      region with high signal. RESULTS: A total of 15 ET patients and 12 "de novo" PD
      patients were evaluated. The area and width of the T1 high signal in the SN
      region were markedly decreased in the PD group compared with the ET and age
      matched controls, and a greater decrease was seen in the ventrolateral segment.
      The neuromelanin measures in the ET group, although slightly lower, were not
      significantly different from the healthy control group. We obtained a sensitivity
      of 66.7% and a specificity of 93.3% in discriminating ET from early-stage PD.
      CONCLUSIONS: Neuromelanin-sensitive MRI techniques can discriminate ET from early
      stage tremor-dominant PD and can be a useful clinical tool in the evaluation of
      tremor disorders. (c) 2015 International Parkinson and Movement Disorder Society.

PMID- 25758365
TI  - Unexpected spreading of G12P[8] rotavirus strains among young children in a small
      area of central Italy.
AB  - Rotavirus gastroenteritis is associated mainly with the five genotypes
      G1,3,4,9P[8] and G2P[4] that are common worldwide, but emerging strains including
      G6, G8, and G12 are also reported sporadically. G12P[8] rotavirus was observed
      unexpectedly to spread in a limited area of Italy during the rotavirus
      surveillance season 2012-2013. All strains were genotyped for VP7 and VP4 and
      subjected to phylogenetic analysis. Amino acid sequences of antigenic regions
      were compared with vaccine and field strains. G12P[8] strains were detected in
      the stools of 52 of 69 (75%) children infected with rotavirus in the central
      Italian region of Umbria. All G12 strains belonged to lineage III, and presented
      the P[8] genotype. Sequence analysis showed close nucleotide identity of both VP4
      and VP7 genes among Umbria G12P[8] strains. The VP7 gene was also similar to
      other G12 strains circulating in different years and countries, and the VP4 gene
      was closely related to other local and global P[8] strains possessing different G
      types. Overall findings suggest either the introduction and evolution of a G12
      VP7 gene into the local Wa-like rotavirus population or the spreading of a strain
      novel for the area. Comparison of the VP8* and VP7 antigenic regions showed high
      conservation between the amino acid sequences of Umbria G12P[8] strains, and
      revealed various substitutions in the VP8* antigenic regions between the Italian
      G12P[8] strains and RotaTeqTM and RotarixTM vaccine strains. The sudden and
      unexpected emergence of G12P[8] rotavirus confirms that these strains have the
      potential to become a sixth common genotype across the world.

PMID- 25758366
TI  - Vision and migraine.
AB  - BACKGROUND: Migraine, a common brain disorder, disrupts vision more than any
      other motor or sensory function. The possible visual aura symptoms vary from
      occasional small flashes of light to complex visual hallucinations, the
      stereotyped teichopsia being the most typical pattern. It is unclear as to why
      aura occurs serendipitously, sometimes preceding, but also occurring after the
      headache, and why aura can present with multiple phenotypes. METHODS: To better
      understand the nature of visual disturbances in migraine, 4 aspects must be
      considered: What are the visual perceptions in migraine; why vision is affected
      in migraine; the role of cortical spreading depression (CSD); how does vision
      could affect migraine. Evidence supporting each of these topics is reviewed.
      RESULTS: CSD travels at a similar pace as the march of symptoms in the visual
      field. Functional neuroimaging studies show spreading changes compatible with CSD
      regardless of aura. Computerized models reproducing the CSD march on the visual
      cortex predict a sensory experience compatible with naturally occurring visual
      auras. Rather than spreading in all directions, these models suggest that CSD
      moves preferentially in one direction. Migraine-preventive drugs increase the CSD
      threshold and reduce CSD velocity. Blind migraineurs may present atypical visual
      aura, with more colors, shorter duration, different shapes, and atypical
      symptoms, such as auditory experiences. CONCLUSIONS: CSD is the underlying
      phenomenon in migraine with and without aura. In migraine without aura, CSD
      probably does not run over silent areas of the cortex, but rather does not reach
      symptomatology threshold. Normal vision is important in migraine, as lack of
      sight may change the visual experience during migraine aura, probably due to
      cortical reorganization and changes in local susceptibility to CSD.

PMID- 25758367
TI  - Chitosan/DsiRNA nanoparticle targeting identifies AgCad1 cadherin in Anopheles
      gambiae larvae as an in vivo receptor of Cry11Ba toxin of Bacillus thuringiensis
      subsp. jegathesan.
AB  - The Cry11Ba protein of Bacillus thuringiensis subsp. jegathesan crystals has
      uniquely high toxicity against a spectrum of mosquito species. The high potency
      of Cry11Ba against Anopheles gambiae is caused by recognition of multiple midgut
      proteins including glycosyl phosphatidylinositol-anchored alkaline phosphatase
      AgALP1, aminopeptidase AgAPN2, alpha-amylase AgAmy1 and alpha-glucosidase Agm3
      that bind Cry11Ba with high affinity and function as putative receptors. The
      cadherin AgCad2 in An. gambiae larvae also binds Cry11Ba with high affinity (Kd =
      12 nM) and is considered a putative receptor, while cadherin AgCad1 bound Cry11Ba
      with low affinity (Kd = 766 nM), a property not supportive for a Cry11Ba receptor
      role. Here, we show the in vivo involvement of AgCad1 in Cry11Ba toxicity in An.
      gambiae larvae using chitosan/DsiRNA nanoparticles to inhibit AgCad expression in
      larvae. Cry11Ba was significantly less toxic to AgCad1-silenced larvae than to
      control larvae. Because AgCad1 was co-suppressed by AgCad2 DsRNAi, the
      involvement of AgCad2 in Cry11Ba toxicity could not be ascertained. The ratio of
      AgCad1:AgCad2 transcript level is 36:1 for gut tissue in 4th instar larvae.
      Silencing AgCad expression had no effect on transcript levels of other binding
      receptors of Cry11Ba. We conclude that AgCad1 and possibly AgCad2 in An. gambiae
      larvae are functional receptors of Cry11Ba toxin in vivo. 

PMID- 25758368
TI  - A proteomic approach to discover and compare interacting partners of
      papillomavirus E2 proteins from diverse phylogenetic groups.
AB  - Papillomaviruses are a very successful group of viruses that replicate
      persistently in localized regions of the stratified epithelium of their specific
      host. Infection results in pathologies ranging from asymptomatic infection,
      benign warts, to malignant carcinomas. Despite this diversity, papillomavirus
      genomes are small (7-8 kbp) and contain at most eight genes. To sustain the
      complex papillomaviral life cycle, each viral protein has multiple functions and
      interacts with and manipulates a plethora of cellular proteins. In this study, we
      use tandem affinity purification and MS to identify host factors that interact
      with 11 different papillomavirus E2 proteins from diverse phylogenetic groups.
      The E2 proteins function in viral transcription and replication and
      correspondingly interact with host proteins involved in transcription, chromatin
      remodeling and modification, replication, and RNA processing. 

PMID- 25758369
TI  - Role of the P-wave high frequency energy and duration as noninvasive
      cardiovascular predictors of paroxysmal atrial fibrillation.
AB  - A normal cardiac activation starts in the sinoatrial node and then spreads
      throughout the atrial myocardium, thus defining the P-wave of the
      electrocardiogram. However, when the onset of paroxysmal atrial fibrillation
      (PAF) approximates, a highly disturbed electrical activity occurs within the
      atria, thus provoking fragmented and eventually longer P-waves. Although this
      altered atrial conduction has been successfully quantified just before PAF onset
      from the signal-averaged P-wave spectral analysis, its evolution during the hours
      preceding the arrhythmia has not been assessed yet. This work focuses on
      quantifying the P-wave spectral content variability over the 2h preceding PAF
      onset with the aim of anticipating as much as possible the arrhythmic episode
      envision. For that purpose, the time course of several metrics estimating
      absolute energy and ratios of high- to low-frequency power in different bands
      between 20 and 200Hz has been computed from the P-wave autoregressive spectral
      estimation. All the analyzed metrics showed an increasing variability trend as
      PAF onset approximated, providing the P-wave high-frequency energy (between 80
      and 150Hz) a diagnostic accuracy around 80% to discern between healthy subjects,
      patients far from PAF and patients less than 1h close to a PAF episode. This
      discriminant power was similar to that provided by the most classical time-domain
      approach, i.e., the P-wave duration. Furthermore, the linear combination of both
      metrics improved the diagnostic accuracy up to 88.07%, thus constituting a
      reliable noninvasive harbinger of PAF onset with a reasonable anticipation. The
      information provided by this methodology could be very useful in clinical
      practice either to optimize the antiarrhythmic treatment in patients at high-risk
      of PAF onset and to limit drug administration in low risk patients. 

PMID- 25758370
TI  - Effects of Zinc and Selenium Supplementation on Thyroid Function in Overweight
      and Obese Hypothyroid Female Patients: A Randomized Double-Blind Controlled
      Trial.
AB  - OBJECTIVE: Zinc (Zn) and selenium (Se) are essential trace elements involved in
      thyroid hormone metabolism. This study was conducted to investigate the effects
      of Zn and Se supplementation on thyroid function of overweight or obese female
      hypothyroid patients in a double-blind, randomized controlled trial. METHODS:
      Sixty-eight female hypothyroid patients were randomly allocated to one of the 4
      supplementation groups receiving Zn + Se (ZS; 30 mg Zn as zinc-gluconate and 200
      MUg Se as high-selenium yeast), Zn + placebo (ZP), Se + placebo (SP), or placebo
      + placebo (PP) for 12 weeks. Serum Zn, Se, free and total triiodothyronine (FT3
      and FT4), free and total thyroxine (FT4 and TT4), thyroid-stimulating hormone
      (TSH), and anthropometric parameters were measured. Dietary intake was recorded
      using 24-hour food recall. Physical activity questionnaire was completed.
      RESULTS: No significant alterations were found in serum Zn or Se concentrations.
      Mean serum FT3 increased significantly in the ZS and ZP groups (p < 0.05) but
      this effect was significant in the ZP group compared to those in SP or PP groups
      (p < 0.05). Mean serum FT4 increased and TSH decreased significantly (p < 0.05)
      in the ZS group. TT3 and TT4 decreased significantly in the SP group (p < 0.05).
      Mean FT3:FT4 ratio was augmented significantly in the ZP group (p < 0.05). No
      significant treatment effects were found for TT3, FT4, TT4, or TSH between
      groups. CONCLUSION: This study showed some evidence of an effect of Zn alone or
      in combination with Se on thyroid function of overweight or obese female
      hypothyroid patients.

PMID- 25758371
TI  - Towards large-cohort comparative studies to define the factors influencing the
      gut microbial community structure of ASD patients.
AB  - Differences in the gut microbiota have been reported between individuals with
      autism spectrum disorders (ASD) and neurotypical controls, although direct
      evidence that changes in the microbiome contribute to causing ASD has been scarce
      to date. Here we summarize some considerations of experimental design that can
      help untangle causality in this complex system. In particular, large cross
      sectional studies that can factor out important variables such as diet,
      prospective longitudinal studies that remove some of the influence of
      interpersonal variation in the microbiome (which is generally high, especially in
      children), and studies transferring microbial communities into germ-free mice may
      be especially useful. Controlling for the effects of technical variables, which
      have complicated efforts to combine existing studies, is critical when biological
      effect sizes are small. Large citizen-science studies with thousands of
      participants such as the American Gut Project have been effective at uncovering
      subtle microbiome effects in self-collected samples and with self-reported diet
      and behavior data, and may provide a useful complement to other types of
      traditionally funded and conducted studies in the case of ASD, especially in the
      hypothesis generation phase. 

PMID- 25758372
TI  - Building a Central Repository for Research Ethics Consultation Data: A Proposal
      for a Standard Data Collection Tool.
AB  - Clinical research ethics consultation services have been established across
      academic health centers over the past decade. This paper presents the results of
      collaboration within the CTSA consortium to develop a standard approach to the
      collection of research ethics consultation information to serve as a foundation
      for quality improvement, education, and research efforts. This approach includes
      categorizing and documenting descriptive information about the requestor,
      research project, the ethical question, the consult process, and describing the
      basic structure for a consult note. This paper also explores challenges in
      determining how to share some of this information between collaborating
      institutions related to concerns about confidentially, data quality, and
      informatics. While there is much still to be learned to improve the process of
      clinical research ethics consultation, these tools can advance these efforts,
      which, in turn, can facilitate the ethical conduct of research. 

PMID- 25758373
TI  - Bone health in phenylketonuria: a systematic review and meta-analysis.
AB  - Patients with Phenylketonuria (PKU) reportedly have decreased bone mineral
      density (BMD). The primary aim of this study was to perform a systematic review
      and meta-analysis to determine the extent and significance of low BMD in early
      treated patients with PKU. Secondary aims were to assess other bone status
      indicators including bone turnover markers (BTM) and to define areas for future
      research. Two research teams (Amsterdam, Netherlands and Atlanta, USA) performed
      literature searches for articles reporting data on BMD, osteopenia and
      osteoporosis, BTM or other bone indicators in patients with PKU. Included
      articles were compared between research teams and assessed for quality and risk
      of bias. A total of 13 unique articles were included; 11/13 articles reported BMD
      including a total of 360 patients. Ten out of 11 articles found BMD was
      significantly lower in patients with PKU. Meta-analyses for total BMD (TBMD; 3
      studies; n = 133), lumbar spine BMD (LBMD; 7 studies; n = 247), and femoral neck
      BMD (FBMD; 2 studies; n = 78) Z-scores were performed. Overall effect sizes were:
      TBMD -0.45 (95% CI -0.61, -0.28); LBMD -0.70 (95% CI -0.82, -0.57); FBMD -0.96
      (95% CI -1.42, -0.49). Definitions of osteopenia and osteoporosis were highly
      heterogeneous between studies and did not align with World Health Organization
      standards and the International Society for Clinical Densitometry positions on
      BMD measurement. Despite individual study findings of low BMD indicating higher
      risk of osteoporosis, pooled available data suggest reduction in BMD is not
      clinically important when using standard definitions of low BMD. Results from
      studies evaluating BTM are inconclusive. Phenylalanine concentration, vitamin D,
      PTH, and nutrient intake do not correlate with BMD or BTM. We recommend
      forthcoming studies use standard definitions of low BMD to determine clinical
      implications of BMD Z-scores below 0, explore cause of low BMD in the subset of
      patients with low BMD for chronological age (Z-score < -2) and assess fracture
      risk in patients with PKU. 

PMID- 25758374
TI  - CORR Insights((r)): synthetic mesh improves shoulder function after
      intraarticular resection and prosthetic replacement of proximal humerus.

PMID- 25758375
TI  - Do Complication Rates Differ by Gender After Metal-on-metal Hip Resurfacing
      Arthroplasty? A Systematic Review.
AB  - BACKGROUND: Although metal-on-metal (MoM) bearing surfaces provide low rates of
      volumetric wear and increased stability, evidence suggests that certain MoM hip
      arthroplasties have high rates of complication and failure. Some evidence
      indicates that women have higher rates of failure compared with men; however, the
      orthopaedic literature as a whole has poorly reported such complications
      stratified by gender. QUESTIONS/PURPOSES: This systematic review aimed to: (1)
      compare the rate of adverse local tissue reaction (ALTR); (2) dislocation; (3)
      aseptic loosening; and (4) revision between men and women undergoing primary MoM
      hip resurfacing arthroplasty (HRA). METHODS: Systematic MEDLINE and EMBASE
      searches identified all level I to III articles published in peer-reviewed
      journals, reporting on the outcomes of interest, for MoM HRA. Articles were
      limited to those with 2-year followup that reported outcomes by gender. Ten
      articles met inclusion criteria. Study quality was evaluated using the Modified
      Coleman Methodology Score; the overall quality was poor. Heterogeneity and bias
      were analyzed using a Mantel-Haenszel statistical method. RESULTS: Women
      demonstrated an increased odds of developing ALTR (odds ratio [OR], 5.70 [2.71
      11.98]; p<0.001), dislocation (OR, 3.04 [1.2-7.5], p=0.02), aseptic loosening
      (OR, 3.18 [2.21-4.58], p<0.001), and revision (OR, 2.50 [2.25-2.78], p<0.001)
      after primary MoM HRA. CONCLUSIONS: A systematic review of the currently
      available literature reveals a higher rate of complications (ALTR, dislocation,
      aseptic loosening, and revision) after MoM HRA in women compared with men.
      Although femoral head size has been frequently implicated as a prime factor in
      the higher rate of complication in women, further research is necessary to
      specifically probe this relationship. Retrospective studies of data available
      (eg, registry data) should be undertaken, and moving forward studies should
      report outcomes by gender (particularly complications). LEVEL OF EVIDENCE: Level
      III, therapeutic study.

PMID- 25758376
TI  - Future patient demand for shoulder arthroplasty by younger patients: national
      projections.
AB  - BACKGROUND: The outcomes of shoulder arthroplasties in younger patients (55 years
      or younger) are not as reliable compared with those of the general population.
      Greater risk of revision and higher complication rates in younger patients
      present direct costs to the healthcare system and indirect costs to the patient
      in terms of quality of life. Previous studies have suggested an increased demand
      for shoulder arthroplasties overall, but to our knowledge, the demand in younger
      patients has not been explored. QUESTIONS/PURPOSES: We asked: (1) What was the
      demand for shoulder arthroplasties between 2002 and 2011 in the United States for
      all patients and a specific subpopulation of patients who were 55 years old or
      younger? (2) How is the demand for shoulder arthroplasties in younger patients
      projected to change through 2030? (3) How is procedural demand projected to
      change in younger patients through 2030, and specifically, what can we anticipate
      in terms of hemiarthroplasty volume compared with that of total shoulder
      arthroplasty? METHODS: We used the National Inpatient Sample database to identify
      primary shoulder arthroplasties performed between 2002 and 2011. A Poisson
      regression model was developed using the National Inpatient Sample data and
      United States Census Bureau projections on future population changes to predict
      estimated national demand for total shoulder arthroplasties and
      hemiarthroplasties in all patients and in the subpopulation 55 years old or
      younger. This model was projected until 2030, with associated 95% CIs. We then
      specifically analyzed the projected demand of hemiarthroplasties and compared
      this with demand for all arthroplasty procedures in the younger patient
      population. RESULTS: Demand for shoulder arthroplasties in patients 55 years or
      younger is increasing at a rate of 8.2% per year (95% CI, 7.06%-9.35%), compared
      with a growth rate of 12.1% (95% CI, 8.35%-16.02%) per year for patients older
      than 55 years. In 2002, 15.9% (3587 of 22,617 captured in the National Inpatient
      Sample) of primary shoulder arthroplasties were performed in patients 55 years
      old or younger. In 2011, the relative size of the younger patient population had
      decreased to 11.0% (7001 of 63,784) of all recipients of shoulder arthroplasties.
      The demand for primary shoulder arthroplasties among younger patients is
      projected to increase by 333.3% (95% CI, 257.0%-432.5%) from 2011 to 2030.
      However, in patients older than 55 years demand is projected to increase by
      755.4% (95% CI, 380.7%-1511.1%). Therefore, despite the increased predicted
      demand for shoulder arthroplasties in younger patients, they are predicted to
      account for only 4% of all recipients by 2030. The rate of hemiarthroplasties in
      patients 55 years or younger showed a 16.5% decline per year (95% CI, 16.1%
      17.1%) from 2002 (53.6% of all arthroplasties) to 2011 (34.2% of all
      arthroplasties). By 2030, hemiarthroplasties are projected to account for only
      23.5% of all shoulder arthroplasties in patients 55 years or younger.
      CONCLUSIONS: The demand for shoulder arthroplasties in younger patients continues
      to increase in the United States; however, rates of hemiarthroplasties are
      declining. The demand has substantial implications for future revision
      arthroplasties, which include the direct healthcare costs of revision
      arthroplasty, the indirect societal burden of missed productivity owing to time
      away from work, and the increased burden of the need for qualified surgeons to
      meet the demand. Despite the increasing rate of arthroplasties performed in
      younger patients, current and projected demands remain greater for older
      patients, indicating a disproportionately greater need for shoulder
      arthroplasties in older patients. This is in contrast to the trends observed in
      the literature regarding hip and knee arthroplasties that show projected demands
      to be greater in younger patients. Factors responsible for the difference in
      demand require further investigation but may be related to changing indications,
      reported poorer outcomes in younger patients, the increased popularity of reverse
      shoulder arthroplasties in the elderly, or the evolution of nonarthroplasty
      options. LEVEL OF EVIDENCE: Level III, prognostic study.

PMID- 25758377
TI  - Analysis of Orthopaedic Research Produced During the Wars in Iraq and
      Afghanistan.
AB  - BACKGROUND: Military orthopaedic surgeons have published a substantial amount of
      original research based on our care of combat-wounded service members and related
      studies during the wars in Iraq and Afghanistan. However, to our knowledge, the
      influence of this body of work has not been evaluated bibliometrically, and doing
      so is important to determine the modern impact of combat casualty research in the
      wider medical community. QUESTIONS/PURPOSES: We sought to identify the 20 most
      commonly cited works from military surgeons published during the Iraq and
      Afghanistan conflicts and analyze them to answer the following questions: (1)
      What were the subject areas of these 20 articles and what was the 2013 Impact
      Factor of each journal that published them? (2) How many citations did they
      receive and what were the characteristics of the journals that cited them? (3) Do
      the citation analysis results obtained from Google Scholar mirror the results
      obtained from Thompson-Reuters' Web of Science? METHODS: We searched the Web of
      Science Citation Index Expanded for relevant original research performed by US
      military orthopaedic surgeons related to Operation Iraqi Freedom and Operation
      Enduring Freedom between 2001 and 2014. Articles citing these studies were
      reviewed using both Web of Science and Google Scholar data. The 20 most cited
      articles meeting inclusion criteria were identified and analyzed by content
      domain, frequency of citation, and sources in which they were cited. RESULTS:
      Nine of these studies examined the epidemiology and outcome of combat injury. Six
      studies dealt with wound management, wound dehiscence, and formation of
      heterotopic ossification. Five studies examined infectious complications of
      combat trauma. The median number of citations garnered by these 20 articles was
      41 (range, 28-264) in Web of Science. Other research citing these studies has
      appeared in 279 different journals, covering 26 different medical and surgical
      subspecialties, from authors in 31 different countries. Google Scholar contained
      97% of the Web of Science citations, but also had 31 duplicate entries and 29
      citations with defective links. CONCLUSIONS: Modern combat casualty research by
      military orthopaedic surgeons is widely cited by researchers in a diverse range
      of subspecialties and geographic locales. This suggests that the military
      continues to be a source of innovation that is broadly applicable to civilian
      medical and surgical practice and should encourage expansion of military-civilian
      collaboration to maximize the utility of the knowledge gained in the treatment of
      war trauma. LEVEL OF EVIDENCE: Level IV, therapeutic study.

PMID- 25758378
TI  - Higher Preoperative Patient Activation Associated With Better Patient-reported
      Outcomes After Total Joint Arthroplasty.
AB  - BACKGROUND: Despite widely reported success associated with hip and knee
      replacements, some patients remain dissatisfied with their outcomes. Patient
      activation, an individual's propensity to engage in adaptive health behaviors,
      has been measured as a potentially important factor contributing to health
      outcomes, cost, and patient experience of care. However, to our knowledge, it has
      not been studied in patients undergoing total joint arthroplasties (TJAs).
      QUESTIONS/PURPOSES: We wanted to determine whether patients with higher
      activation scores would experience (1) greater resolution of pain and improved
      activity, (2) greater improvements in postoperative physical and mental health,
      and (3) greater patient satisfaction after primary THA or TKA. METHODS: We
      approached 174 patients and enrolled 135 who were undergoing primary THA or TKA
      at one of two hospitals between January 2013 and May 2014. Patient Activation
      Measure (PAM) scores were obtained preoperatively and patient-reported outcomes
      were assessed and completed for 125 patients pre- and postoperatively at the 6-
      or 12-month visit. We assessed pain and activity with the Hip Disability and
      Osteoarthritis Outcome Score (HOOS), Knee Injury and Osteoarthritis Outcome Score
      (KOOS), and University of California Los Angeles (UCLA) activity scores. We
      measured physical and mental health by calculating SF12v2(r) scores and measured
      patient satisfaction with the Hip and Knee Satisfaction Scale (HKSS). Linear
      regression models were used to test the association between baseline PAM and
      postoperative patient-reported outcomes. RESULTS: Overall, patients with a higher
      baseline PAM score experienced better pain relief using the HOOS/KOOS pain scores
      (R2=0.311, p=0.048) and symptoms using the HOOS/KOOS symptom scores (R2=0.272,
      p=0.021). In addition, higher PAM scores were associated with better
      postoperative mental health using the SF12v2(r) (R2=0.057, p<0.001), but were not
      associated with higher physical health (R2=0.176, p=0.173). Finally, higher PAM
      scores were associated with having greater postoperative satisfaction after
      surgery using the HKSS questionnaire (R2=0.048, p=0.023). CONCLUSIONS: Higher
      preoperative patient activation was associated with better pain relief, decreased
      symptoms, improved mental health, and greater satisfaction after TJA. Future
      efforts should be aimed at studying if improving patient activation before
      surgery results in better patient-reported outcomes after elective THA or TKA.
      LEVEL OF EVIDENCE: Level II, prognostic study.

PMID- 25758380
TI  - Assessing alcohol problems: need for a thorough medication history.

PMID- 25758381
TI  - Creating nanoparticle stability in ionic liquid [C4mim][BF4] by inducing
      solvation layering.
AB  - The critical role of solvation forces in dispersing and stabilizing nanoparticles
      and colloids in 1-butyl-3-methylimidazolium tetrafluoroborate [C4mim][BF4] is
      demonstrated. Stable silica nanoparticle suspensions over 60 wt % solids are
      achieved by particle surface chemical functionalization with a fluorinated
      alcohol. A combination of techniques including rheology, dynamic light scattering
      (DLS), transmission electron microscopy (TEM), and small angle neutron scattering
      (SANS) are employed to determine the mechanism of colloidal stability. Solvation
      layers of ~5 nm at room temperature are measured by multiple techniques and are
      thought to be initiated by hydrogen bonds between the anion [BF4](-) and the
      fluorinated group on the surface coating. Inducing structured solvation layering
      at particle surfaces through hydrogen bonding is demonstrated as a method to
      stabilize particles in ionic liquids. 

PMID- 25758379
TI  - A High-grade Sarcoma Arising in a Patient With Recurrent Benign Giant Cell Tumor
      of the Proximal Tibia While Receiving Treatment With Denosumab.
AB  - BACKGROUND: A giant cell tumor of bone is a primary benign but locally aggressive
      neoplasm. Malignant transformation in a histologically typical giant cell tumor
      of bone, without radiotherapy exposure, is an uncommon event, occurring in less
      than 1% of giant cell tumors of bone. Although surgery is the standard initial
      treatment, denosumab, a monoclonal antibody drug that inhibits receptor activator
      of nuclear factor-kappaB ligand (RANKL), has shown considerable activity
      regarding disease and control of symptoms in patients with recurrence,
      unresectable, and metastatic giant cell tumors of bone. CASE DESCRIPTION: We
      report the case of a 20-year-old woman with a recurrent benign, giant cell tumor
      of bone, who had a bone sarcoma develop while receiving denosumab treatment.
      LITERATURE REVIEW: To our knowledge, there have been no reports of infection or
      malignancy with low-dose denosumab administration for osteoporosis. However,
      while there are relatively few reported side effects, the safety of denosumab and
      adverse events seen with higher doses, as used in treatment of giant cell tumors
      of bone are not well defined. CLINICAL RELEVANCE: Denosumab has become a valuable
      adjunct for treatment of recurrent or unresectable giant cell tumor of bone. It
      is not clear if our patient's malignant transformation of a giant cell tumor of
      bone while receiving denosumab treatment was caused by denosumab, but it is
      important to be aware of the possibility if more cases occur. Future studies
      should focus on the safety of high-dose denosumab administration in patients with
      a benign unresectable giant cell tumor of bone.

PMID- 25758382
TI  - Survival probability of beneficial mutations in bacterial batch culture.
AB  - The survival of rare beneficial mutations can be extremely sensitive to the
      organism's life history and the trait affected by the mutation. Given the
      tremendous impact of bacteria in batch culture as a model system for the study of
      adaptation, it is important to understand the survival probability of beneficial
      mutations in these populations. Here we develop a life-history model for
      bacterial populations in batch culture and predict the survival of mutations that
      increase fitness through their effects on specific traits: lag time, fission
      time, viability, and the timing of stationary phase. We find that if beneficial
      mutations are present in the founding population at the beginning of culture
      growth, mutations that reduce the mortality of daughter cells are the most likely
      to survive drift. In contrast, of mutations that occur de novo during growth,
      those that delay the onset of stationary phase are the most likely to survive.
      Our model predicts that approximately fivefold population growth between
      bottlenecks will optimize the occurrence and survival of beneficial mutations of
      all four types. This prediction is relatively insensitive to other model
      parameters, such as the lag time, fission time, or mortality rate of the
      population. We further estimate that bottlenecks that are more severe than this
      optimal prediction substantially reduce the occurrence and survival of adaptive
      mutations.

PMID- 25758385
TI  - Reducing obesity prejudice in medical education.
AB  - BACKGROUND: Healthcare worker attitudes toward obese individuals facilitate
      discrimination and contribute to poor health outcomes. Previous studies have
      demonstrated medical student bias toward obese individuals, but few have examined
      effects of the educational environment on these prejudicial beliefs. We sought to
      determine whether an innovative educational intervention (reading a play about
      obesity) could diminish obesity prejudice relative to a standard medical lecture.
      METHODS: We conducted a randomized, controlled trial enrolling medical students
      (n = 129) from three universities. Students were assigned to play-reading or a
      standard lecture. Explicit attitudes and implicit bias toward obese individuals
      were assessed prior to intervention and after four months. RESULTS: At baseline,
      students demonstrated moderate explicit and implicit bias toward obese people
      despite high scores on empathy. Students randomized to the play-reading group had
      significantly decreased explicit fat bias (P = 0.01) at follow-up, while students
      in the lecture group showed increased endorsement of a prescriptive model of care
      at the expense of a patient-centered approach (P = 0.03). There was a significant
      increase in empathy for those in both the theater (P = 0.007) and lecture group
      (P = 0.02). The intervention had no significant effect on implicit bias or regard
      for obesity as a civil rights issue. DISCUSSION: Dramatic reading may be superior
      to traditional medical lectures for showcasing patient rights and preferences.
      The present study demonstrates for the first time that play-reading diminishes
      conscious obesity bias. Further research should determine whether nontraditional
      methods of instruction promote improved understanding of and care for obese
      patients.

PMID- 25758386
TI  - The perceived relevance of tooth carving in dental education: Views of practicing
      dentists and faculty in West India.
AB  - BACKGROUND: Teaching dental anatomy includes observation and analysis of natural
      teeth and carving wax models to accurately reproduce the morphology of teeth. The
      aim of this survey was to assess the importance of tooth carving in its relevance
      to clinical practice in the opinion of practicing clinicians throughout west
      India. METHODS: Faculties of 27 dental colleges and dental practitioners of the
      Rajasthan and Gujarat states in western India were contacted through e-mail,
      telephone and mail. A total of 1866 subjects were contacted of which 1722
      responded. The perceived relevance of tooth carving in clinical practice was
      assessed through a 14-item multiple choice questionnaire. Questions ranged from
      the queries of clinicians' interest in tooth carvings, their opinion of the
      practical significance of this exercise during their training to their clinical
      practice, and their recommendations regarding tooth carving. RESULTS: A total of
      69.1% of respondent practitioners believe that the tooth carving exercise
      influences their clinical practice, and 93.4% recommend tooth carving to be
      continued in the undergraduate dental curriculum. DISCUSSION: The results
      indicated that most dentists in west India valued what they learned through tooth
      carving and that they use this knowledge in their practice. This information
      supports the continued teaching of tooth carving in the undergraduate dental
      curriculum.

PMID- 25758387
TI  - Implementing a skillslab training program in a developing country.
AB  - BACKGROUND: Eight skills laboratories (skillslabs) were established by consensus
      of Vietnamese medical universities, with international support. A national list
      of basic skills needed for medical practice and suitable for skillslab training
      was developed; models, medical and teaching equipment were supplied; learning
      material was developed and core staff and teachers were trained. This study was
      designed to assess how closely eight schools in Vietnam came to implementing all
      recommended skills on list developed by educators of that country, and identify
      the facilitating factors and barriers to skillslab use within the country's
      largest school. METHODS: Data were collected from reports from the eight
      skillslabs. Students and trainers from the largest university were surveyed for
      their perceptions of the quality of training on eight selected skills. Results of
      students' skill assessments were gathered, and focus group discussions with
      trainers were conducted. SPSS 16 was used to analyze the quantitative data and
      cluster analysis was used to test for differences. RESULTS: Only one medical
      school was able to train all 56 basic skills proposed by consensus among the
      eight Vietnamese medical universities. Deeper exploration within the largest
      school revealed that its skillslab training was successful for most skills,
      according to students' postprogram skills assessment and to students' and
      trainers' perceptions. However, through focus group discussions we learned that
      the quantity of training aids was perceived to be insufficient; some
      models/manikins were inappropriate for training; more consideration was needed in
      framing the expected requirements of students within each skill; too little time
      was allocated for the training of one of the eight skills investigated; and
      further curriculum development is needed to better integrate the skills training
      program into the broader curriculum. DISCUSSION: The fact that one medical school
      could teach all skills recommended for skillslab training demonstrates that all
      Vietnamese schools may be similarly able to teach the basic skills of the
      national consensus list. But as of now, it remains challenging for most schools
      in this developing country to fully implement a national skillslab training
      program.

PMID- 25758388
TI  - The intricate relationship between a medical school and a teaching hospital: A
      case study in Uganda.
AB  - BACKGROUND: The relationship between medical schools and teaching hospitals is
      full of opportunities but also challenges even though they have complementary
      goals that could enhance each other. Although medical schools and teaching
      hospitals may face some similar challenges around the world, there could be
      context-specific observations that differ in resource-rich versus resource
      limited settings. The purpose of this study was to investigate factors that are
      perceived to have influenced the relationship between a medical school and a
      teaching hospital in Uganda, a resource-limited setting. METHODS: This was a
      cross-sectional, descriptive study in which key informant individual interviews
      were conducted with senior administrators and senior staff members of the Mulago
      Hospital and Makerere University Medical School. The interviews explored factors
      perceived to have favoured the working relationship between the two institutions,
      challenges faced and likely future opportunities. Both quantitative and
      qualitative data were generated. Thematic analysis was used with the qualitative
      data. RESULTS: Respondents reported a strained relationship between the two
      institutions, with unfavourable factors far outweighing the favourable factors
      influencing the relationship. Key negative reported factors included having
      different administrative set-ups, limited opportunities to share funds and to
      forge research collaborations, unexploited potential of sharing human resources
      to address staff shortages, as well as a lack of a memorandum of understanding
      between the two institutions. DISCUSSION: This study identifies barriers in the
      existing relationship between a teaching hospital and medical college in a
      resource-poor country. It proposes a collaborative model, rather than competitive
      model, for the two institutions that may work in both resource-limited and
      resource-rich settings.

PMID- 25758389
TI  - Online faculty development for creating E-learning materials.
AB  - BACKGROUND: Faculty who want to develop e-learning materials face pedagogical
      challenges of transforming instruction for the online environment, especially as
      many have never experienced online learning themselves. They face technical
      challenges of learning new software and time challenges of not all being able to
      be in the same place at the same time to learn these new skills. The objective of
      the Any Day Any Place Teaching (ADAPT) faculty development program was to create
      an online experience in which faculty could learn to produce e-learning
      materials. METHODS: The ADAPT curriculum included units on instructional design,
      copyright principles and peer review, all for the online environment, and units
      on specific software tools. Participants experienced asynchronous and synchronous
      methods, including a learning management system, PC-based videoconferencing,
      online discussions, desktop sharing, an online toolbox and optional face-to-face
      labs. Project outcomes were e-learning materials developed and participants'
      evaluations of the experience. Likert scale responses for five instructional
      units (quantitative) were analyzed for distance from neutral using one-sample t
      tests. Interview data (qualitative) were analyzed with assurance of data
      trustworthiness and thematic analysis techniques. RESULTS: Participants were 27
      interprofessional faculty. They evaluated the program instruction as easy to
      access, engaging and logically presented. They reported increased confidence in
      new skills and increased awareness of copyright issues, yet continued to have
      time management challenges and remained uncomfortable about peer review. They
      produced 22 new instructional materials. DISCUSSION: Online faculty development
      methods are helpful for faculty learning to create e-learning materials.
      Recommendations are made to increase the success of such a faculty development
      program.

PMID- 25758390
TI  - Introduction of Mini-CEX in undergraduate dental education in India.
AB  - BACKGROUND: Some assessment methods of clinical learners have limitations so that
      students might not reflect their performance in actual clinical situations.
      Educational research has so far not yielded a single 'gold-standard' performance
      assessment tool. Mini-CEX (clinical evaluation exercise) is an instrument
      intended for work-based assessment of actual clinical performance, including a
      range of skills like communication and humanistic qualities. It involves direct
      observation of real patient encounters followed by one-on-one structured feedback
      sessions between assessors and the trainees. Mini-CEX has already found wide
      acceptance in medical education but is largely untested in dental education.
      METHODS: Twelve dental undergraduate students underwent one mini-CEX encounter
      each. Four teachers performed the roles of assessors, directly observing the
      students and rating their performance using the standardized mini-CEX rating
      form. A systematic feedback session then took place, following which students'
      and teachers' perception of the mini-CEX was sought through structured
      questionnaires. RESULTS: Almost all students appreciated that their communication
      skills were assessed, but some felt that the presence of a teacher was
      intimidating. They felt that the constructive feedback helped them reinforce the
      skills that they did well. The assessors found planning for mini-CEX time
      consuming and also felt that that their presence had an impact on the students'
      performance. However, teachers reported that the mini-CEX allows them to assess
      students' professionalism and communication skills, which are important in
      dentistry. DISCUSSION: Data from this pilot study supports the use of mini-CES in
      dental education, but still the need for wider studies remains. It also explains
      the ways in which undergraduate dental students and teachers find the mini-CEX
      useful and how it could be improved and used more effectively.

PMID- 25758391
TI  - A 360-degree evaluation of the communication and interpersonal skills of medicine
      resident physicians in Pakistan.
AB  - BACKGROUND: To provide high-quality patient care, effective communication and
      interpersonal skills are necessary for physicians. A 360-degree evaluation of
      residents in the department of medicine was conducted to assess their
      interpersonal and communication skills. The measurement properties and utility of
      the multi-source ratings were investigated. METHODS: A cross-sectional assessment
      of a cohort of Internal Medicine residents was conducted at the Aga Khan Medical
      University in Pakistan. Every resident (n = 49) was evaluated by eight raters,
      including physicians, nurses and unit staff. Each resident also completed a self
      evaluation. Evidence to support the validity of the ratings was gathered by
      exploring performance differences amongst more- and less-experienced providers.
      Analysis of variance (ANOVA) was employed to test for differences in mean scores,
      both for rater type and experience (residency year). Generalizability theory was
      employed to estimate the reliability of the ratings. RESULTS: We received 367/441
      (83.2%) completed forms. There was a significant effect attributable to rater
      source (F = 5.2, P < 0.01). There were no significant differences in mean scores
      for residents at different levels of training. The mean resident self-assessment
      scores were significantly lower than those provided by faculty (P < 0.01). Based
      on eight raters, the reliability of the ratings was moderate (rho2 = 0.39).
      DISCUSSION: The 360-degree evaluation technique can be used to measure the
      communication and interpersonal skills of residents. It can also provide
      important data to guide resident feedback. Health care providers and staff who
      interact with residents on regular basis can, as a group provide moderately
      consistent judgments of their abilities.

PMID- 25758392
TI  - Overcoming challenges to develop pediatric postgraduate training programs in low-
      and middle-income countries.
AB  - BACKGROUND: Interest is growing in strengthening postgraduate medical education
      in low-income countries. The purpose of this study was to understand how
      postgraduate pediatric training programs are developed in countries with no or
      few pediatric training opportunities. The authors sought to describe and compare
      a purposive sample of such new programs, and identify challenges and solutions
      for successful program establishment and sustainability. METHODS: The authors
      queried national pediatric email lists and the Accreditation Council for Graduate
      Medical Education (ACGME) accredited pediatric residency programs in the United
      States to identify four pediatric training programs that met study criteria. All
      four programs responded to a questionnaire with quantitative and qualitative
      components. Qualitative responses were analyzed for themes. RESULTS: Four centers
      - in Kenya, Laos, Eritrea and Cambodia - met study criteria. Reported challenges
      to program development and sustainability centered on faculty development and
      retention, training in pediatric subspecialties, creating pipelines for
      applicants and graduates, and funding. These themes were used to develop a logic
      model, which provides a framework for planning, implementing and evaluating new
      postgraduate general pediatric training program in low-income countries.
      DISCUSSION: This study compares four postgraduate general pediatric training
      programs that were recently established and now continue to graduate pediatric
      residents in low-income countries. Lessons derived from these programs may help
      guide practice and research for other centers seeking to establish similar
      programs.

PMID- 25758393
TI  - A framework for revising preservice curriculum for nonphysician clinicians: The
      mozambique experience.
AB  - Mozambique, with approximately 0.4 physicians and 4.1 nurses per 10,000 people,
      has one of the lowest ratios of health care providers to population in the world.
      To rapidly scale up health care coverage, the Mozambique Ministry of Health has
      pushed for greater investment in training nonphysician clinicians, Tiotacnicos de
      Medicina (TM). Based on identified gaps in TM clinical performance, the Ministry
      of Health requested technical assistance from the International Training and
      Education Center for Health (I-TECH) to revise the two-and-a-half-year preservice
      curriculum. A six-step process was used to revise the curriculum: (i) Conducting
      a task analysis, (ii) defining a new curriculum approach and selecting an
      integrated model of subject and competency-based education, (iii) revising and
      restructuring the 30-month course schedule to emphasize clinical skills, (iv)
      developing a detailed syllabus for each course, (v) developing content for each
      lesson, and (vi) evaluating implementation and integrating feedback for ongoing
      improvement. In May 2010, the Mozambique Minister of Health approved the revised
      curriculum, which is currently being implemented in 10 training institutions
      around the country. Key lessons learned: (i) Detailed assessment of training
      institutions' strengths and weaknesses should inform curriculum revision. (ii)
      Establishing a Technical Working Group with respected and motivated clinicians is
      key to promoting local buy-in and ownership. (iii) Providing ready-to-use
      didactic material helps to address some challenges commonly found in resource
      limited settings. (iv) Comprehensive curriculum revision is an important first
      step toward improving the quality of training provided to health care providers
      in developing countries. Other aspects of implementation at training institutions
      and health care facilities must also be addressed to ensure that providers are
      adequately trained and equipped to provide quality health care services. This
      approach to curriculum revision and implementation teaches several key lessons,
      which may be applicable to preservice training programs in other less developed
      countries. 

PMID- 25758394
TI  - Self-directed learning readiness among fifth semester MBBS students in a teaching
      institution of South India.
AB  - BACKGROUND: Lifelong learning is a skill that must be acquired by medical
      graduates and proposes that students take the responsibility for learning
      process. The present study was carried out to measure readiness for self-directed
      learning among fifth semester MBBS studentsin a tertiary care teaching hospital.
      METHODS: Readiness assessment was carried out among 87 fifth semester MBBS
      students using Fishers' 40-item self-directed learning readiness score (SDLRS)
      instrument after taking informed written consent. A total of 40 items were
      classified into three domains: Self-management (9 items), desire for learning (16
      items) and self-control (15 items). Institute scientific society and ethical
      committee clearance was obtained. The data were entered and analyzed using IBM
      SPSS version 21. Chi-square test was used to elicit relationship between
      readiness assessment and gender, presence of a physician in family and area of
      residence. RESULTS: Out of 87 students, 64 (73.5%) students consented to be
      assessed for readiness toward self-directed learning. The mean SDLRS score was
      140.4 +/- 24.4, with 19 students (30%) scoring more than 150 indicating high
      readiness.The mean scores in the three domains of self-management, desire for
      learning and self-control were 38.8 +/- 9.8, 47.3 +/- 6.9 and 54.3 +/- 10.4,
      respectively. Males had a higher readiness for self-directed learning than
      females (P = 0.045). DISCUSSION: Self-directed learning scores were lower among
      our MBBS students than reported elsewhere in the literature.

PMID- 25758395
TI  - The awareness and attitudes of students of one indian dental school toward
      information technology and its use to improve patient care.
AB  - BACKGROUND: Many obstacles need to be overcome if digital and electronic
      technologies are to be fully integrated in the operation of dental clinics in
      some countries. These obstacles may be physical, technical, or psychosocial
      barriers in the form of perceptions and attitudes related to software
      incompatibilities, patient privacy, and interference with the patient
      practitioner relationship. The objectives of the study are to assess the
      perceptions of Indian dental students of one school toward the usefulness of
      digital technologies in improving dental practice; their willingness to use
      digital and electronic technologies; the perceived obstacles to the use of
      digital and electronic technologies in dental care setups; and their attitudes
      toward Internet privacy issues. METHODS: The study population consisted of 186
      final year undergraduate dental students from the A. B. Shetty Memorial institute
      of Dental Sciences, Rajiv Gandhi University of Health Sciences, Mangalore, India.
      Survey data were analyzed descriptively . RESULTS: Most students indicated that
      information technology enhances patient satisfaction, the quality of dental
      record, diagnosis, treatment planning, and doctor-doctor communication. Cost of
      equipment and need for technical training were regarded as major obstacles by
      substantial proportions of respondents. DISCUSSION: Most dental students at our
      school feel that the information technology will support their decision making in
      diagnoses and devising effective treatment plans, which in turn increase patient
      satisfaction and quality of care. Students also perceived that lack of technical
      knowledge and the high cost of implementation are major barriers to developing
      information technology in India.

PMID- 25758396
TI  - Hand hygiene and health care hierarchy: A resident's perspective.

PMID- 25758397
TI  - A plea to preserve the sanctity of a "Textbook".

PMID- 25758398
TI  - Recent 2015 changes to the UK foundation training application: A deterrent to
      medical student research?

PMID- 25758399
TI  - Beyond evidence-based medicine : Need for a new paradigm in patient care
      delivery.

PMID- 25758400
TI  - Globalisation of social media : An unfair occurrence in medical education?

PMID- 25758401
TI  - Cognitive Aids in Medicine Assessment Tool (CMAT): preliminary validation of a
      novel tool for the assessment of emergency cognitive aids.
AB  - Applying human factors principles to the design of clinical emergency guidelines
      is important. The UK Civil Aviation Authority uses a Checklist Assessment Tool
      for evaluating the content and usability of emergency drills before introduction
      into service on aircraft. We hypothesised that this model could be used to
      develop a generic medical tool. A three-stage modified Delphi process was used to
      adapt the above tool for use in designing medical emergency guidelines. The
      resulting Cognitive aids in Medicine Assessment Tool was then used to score and
      rank seven published difficult airway guidelines; the scores were used to assess
      its validity and reliability. Pearson's rank coefficient between these scores and
      scores from independent assessors was 0.89 (p = 0.007). Internal consistency, as
      assessed by Cronbach's alpha, was 0.74, 0.96 and 0.72 for the tool's three
      constituent domains of physical characteristics, content and layout/format,
      respectively. Inter-rater reliability, as assessed by Cohen's kappa, ranged from
      0.33 to 0.72. The adoption of our tool has the potential to improve the usability
      of medical emergency guidelines.

PMID- 25758402
TI  - Hi-Jack: a novel computational framework for pathway-based inference of host
      pathogen interactions.
AB  - MOTIVATION: Pathogens infect their host and hijack the host machinery to produce
      more progeny pathogens. Obligate intracellular pathogens, in particular, require
      resources of the host to replicate. Therefore, infections by these pathogens lead
      to alterations in the metabolism of the host, shifting in favor of pathogen
      protein production. Some computational identification of mechanisms of host
      pathogen interactions have been proposed, but it seems the problem has yet to be
      approached from the metabolite-hijacking angle. RESULTS: We propose a novel
      computational framework, Hi-Jack, for inferring pathway-based interactions
      between a host and a pathogen that relies on the idea of metabolite hijacking. Hi
      Jack searches metabolic network data from hosts and pathogens, and identifies
      candidate reactions where hijacking occurs. A novel scoring function ranks
      candidate hijacked reactions and identifies pathways in the host that interact
      with pathways in the pathogen, as well as the associated frequent hijacked
      metabolites. We also describe host-pathogen interaction principles that can be
      used in the future for subsequent studies. Our case study on Mycobacterium
      tuberculosis (Mtb) revealed pathways in human-e.g. carbohydrate metabolism,
      lipids metabolism and pathways related to amino acids metabolism-that are likely
      to be hijacked by the pathogen. In addition, we report interesting potential
      pathway interconnections between human and Mtb such as linkage of human fatty
      acid biosynthesis with Mtb biosynthesis of unsaturated fatty acids, or linkage of
      human pentose phosphate pathway with lipopolysaccharide biosynthesis in Mtb.
      AVAILABILITY AND IMPLEMENTATION: Datasets and codes are available at
      http://cloud.kaust.edu.sa/Pages/Hi-Jack.aspx

PMID- 25758404
TI  - Cardiovascular effects of pimobendan in healthy mature horses.
AB  - REASONS FOR PERFORMING STUDY: Pimobendan is an inodilator used in dogs for the
      management of heart failure due to myxomatous valve disease or dilated
      cardiomyopathy. The lack of data regarding the effects of pimobendan in horses
      prevents the rational use of this drug. OBJECTIVE: To determine the
      cardiovascular effects of pimobendan in healthy mature horses. STUDY DESIGN:
      Randomised experimental study. METHODS: Five horses were fasted overnight prior
      to receiving i.v. pimobendan (0.25 mg/kg bwt), intragastric (i.g.) pimobendan
      (0.25 mg/kg bwt) or i.g. placebo with a washout period of one week between each
      administration. Horses were instrumented for the measurement of right ventricular
      (RV) minimum pressure, RV maximum pressure, RV end diastolic pressure, and
      maximum rate of increase and decrease in RV pressure before and 0.5, 1, 2, 4, and
      8 h after drug administration. Arterial blood pressure, central venous pressure,
      cardiac output and heart rate were measured at the same time points. Data were
      expressed as a maximum percentage of change over baseline values. RESULTS: There
      were no adverse effects associated with administration of pimobendan. The
      percentage increase in heart rate was significantly greater for horses given
      pimobendan i.g. (33 +/- 4%) and i.v. (36 +/- 14%) than for those given a placebo
      (-2 +/- 7%). The percentage increase in maximum rate of increase in RV pressure
      (35 +/- 36%) and the percentage decrease in minimum pressure (47 +/- 24%) and end
      diastolic pressure (34 +/- 13%) were significantly greater in horses given
      pimobendan i.v. than in those given placebo. Other variables measured were not
      significantly different between treatment groups. CONCLUSION: Pimobendan
      administered i.v. has positive chronotropic and inotropic effects in healthy
      mature horses and warrants further investigation for the treatment of heart
      failure in horses.

PMID- 25758403
TI  - Kisspeptin signaling in the amygdala modulates reproductive hormone secretion.
AB  - Kisspeptin (encoded by KISS1) is a crucial activator of reproductive function.
      The role of kisspeptin has been studied extensively within the hypothalamus but
      little is known about its significance in other areas of the brain. KISS1 and its
      cognate receptor are expressed in the amygdala, a key limbic brain structure with
      inhibitory projections to hypothalamic centers involved in gonadotropin
      secretion. We therefore hypothesized that kisspeptin has effects on neuronal
      activation and reproductive pathways beyond the hypothalamus and particularly
      within the amygdala. To test this, we mapped brain neuronal activity (using
      manganese-enhanced MRI) associated with peripheral kisspeptin administration in
      rodents. We also investigated functional relevance by measuring the gonadotropin
      response to direct intra-medial amygdala (MeA) administration of kisspeptin and
      kisspeptin antagonist. Peripheral kisspeptin administration resulted in a marked
      decrease in signal intensity in the amygdala compared to vehicle alone. This was
      associated with an increase in luteinizing hormone (LH) secretion. In addition,
      intra-MeA administration of kisspeptin resulted in increased LH secretion, while
      blocking endogenous kisspeptin signaling within the amygdala by administering
      intra-MeA kisspeptin antagonist decreased both LH secretion and LH pulse
      frequency. We provide evidence for the first time that neuronal activity within
      the amygdala is decreased by peripheral kisspeptin administration and that
      kisspeptin signaling within the amygdala contributes to the modulation of
      gonadotropin release and pulsatility. Our data suggest that kisspeptin is a
      'master regulator' of reproductive physiology, integrating limbic circuits with
      the regulation of gonadotropin-releasing hormone neurons and reproductive hormone
      secretion.

PMID- 25758405
TI  - The impact of genetics on the management of patients on warfarin awaiting
      surgery.
AB  - Two older patients with atrial fibrillation, receiving warfarin for
      thromboembolic prophylaxis, with a target range of 2.0-3.0, were significantly
      over anticoagulated prior to elective intervention, in spite of having adhered to
      the standard protocol of 5 days of warfarin interruption. Neither patient had any
      abnormality of liver function nor was taking any interacting drug known to
      inhibit warfarin metabolism or affect sensitivity to warfarin. Both had variant
      cytochrome P2C9 (CYP2C9) alleles which reduce the metabolic capacity of the
      CYP2C9 enzyme responsible for the metabolism of the S-warfarin enantiomer. Need
      for preoperative administration of vitamin K or postponement of an operation
      because of an INR >1.5 could be explained by variant alleles for CYP2C9 and age. 

PMID- 25758406
TI  - Who has undiagnosed dementia? A cross-sectional analysis of participants of the
      Aging, Demographics and Memory Study.
AB  - BACKGROUND: delays in diagnosing dementia may lead to suboptimal care, yet around
      half of those with dementia are undiagnosed. Any strategy for case finding should
      be informed by understanding the characteristics of the undiagnosed population.
      We used cross-sectional data from a population-based sample with dementia aged 71
      years and older in the United States to describe the undiagnosed population and
      identify factors associated with non-diagnosis. METHODS: the Aging, Demographics
      and Memory Study (ADAMS) Wave A participants (N = 856) each underwent a detailed
      neuropsychiatric investigation. Informants were asked whether the participant had
      ever received a doctor's diagnosis of dementia. We used multiple logistic
      regression to identify factors associated with informant report of a prior
      dementia diagnosis among those with a study diagnosis of dementia. RESULTS: of
      those with a study diagnosis of dementia (n = 307), a prior diagnosis of dementia
      was reported by 121 informants (weighted proportion = 42%). Prior diagnosis was
      associated with greater clinical dementia rating (CDR), from 26% (CDR = 1) to 83%
      (CDR = 5). In multivariate analysis, those aged 90 years or older were less
      likely to be diagnosed (P = 0.008), but prior diagnosis was more common among
      married women (P = 0.038) and those who had spent more than 9 years in full-time
      education (P = 0.043). CONCLUSIONS: people with dementia who are undiagnosed are
      older, have fewer years in education, are more likely to be unmarried, male and
      have less severe dementia than those with a diagnosis. Policymakers and
      clinicians should be mindful of the variation in diagnosis rates among subgroups
      of the population with dementia.

PMID- 25758407
TI  - Social vulnerability and survival across levels of frailty in the Honolulu-Asia
      Aging Study.
AB  - PURPOSE: we evaluated mortality risk in relation to social vulnerability across
      levels of frailty among a cohort of older Japanese-American men. METHODS: in
      secondary analysis of the Honolulu-Asia Aging Study (HAAS), participants (n =
      3,271) were aged 72-93 years at baseline. A frailty index (FI) created using 58
      potential health deficits to quantify participants' frailty level at baseline,
      with four frailty strata: 0.0 < FI <= 0.1 (n = 1,074); 0.1 < FI <= 0.20 (n =
      1,549); 0.2 < FI <= 0.30 (n = 472); FI > 0.3 (n = 176). Similarly, a social
      vulnerability index was created using 19 self-reported social deficits. Cox
      proportional hazard modelling was employed to estimate the impact of social
      vulnerability across the four levels of frailty, accounting for age, smoking,
      alcohol use and variation in health deficits within each frailty level. RESULTS:
      for the fittest participants, social vulnerability was associated with mortality
      (hazards ratio (HR) = 1.04, 95% confidence interval (CI) = 1.01, 1.07; P value =
      0.008). Similarly, for those considered at risk for frailty, each social deficit
      was associated with a 5% increased risk of mortality. For frail individuals, the
      Cox regression analyses indicated that social vulnerability was not significantly
      associated with mortality (0.2 < FI <= 0.3: HR = 1.016, 95% CI = 0.98, 1.06; P
      value = 0.442; FI > 0.3: HR = 0.98, 95% CI = 0.93, 1.04). CONCLUSIONS: for the
      fittest and at-risk HAAS participants, the accumulation of social deficits was
      associated with significant increases in mortality risk. For frail individuals
      (FI > 0.20), the estimation of mortality risk may depend more so on intrinsic
      factors related to their health.

PMID- 25758408
TI  - Additional standing balance circuit classes during inpatient rehabilitation
      improved balance outcomes: an assessor-blinded randomised controlled trial.
AB  - OBJECTIVE: to evaluate the impact on balance (postural control) of six 1-h
      circuit classes that targeted balance in addition to usual therapy for
      rehabilitation inpatients. DESIGN: a randomised controlled trial with 2-week and
      3-month follow-up. PARTICIPANTS: one hundred and sixty-two general rehabilitation
      inpatients, Bankstown-Lidcombe Hospital, Australia. INTERVENTION: intervention
      group participants received six 1-h circuit classes over a 2-week period in
      addition to usual therapy. Control group participants received usual therapy.
      RESULTS: standing balance performance (primary outcome) was better in the
      intervention group than in the control group at 2 weeks (between-group difference
      after adjusting for baseline values 3.3 s; 95% confidence interval (CI) 0.84 to
      5.7, P = 0.009), but the between-group difference was not statistically
      significant at 3 months (3.4 s; 95% CI -0.56 to 7.38, P = 0.092). Intervention
      group outcomes were significantly better than the control groups for mobility
      performance (Short Physical Performance Battery) at 2 weeks (1.19, 95% CI 0.52 to
      1.87, P <0.01) and 3 months (1.00, 95% CI 0.00 to 2.00, P < 0.049) and self
      reported functioning (AM-PAC) at 2 weeks (5.39, 95% CI 1.20 to 9.57, P = 0.012).
      The intervention group had a 4.1-day shorter rehabilitation unit stay (95% CI 
      8.3 to 0.16, P = 0.059) and a lower risk of readmission in the 3 months after
      randomisation (incidence rate ratio 0.70, 95% CI 0.42 to 1.18, P = 0.184), but
      these differences were not statistically significant. CONCLUSION: two weeks of
      standing balance circuit classes in addition to usual therapy improved balance in
      general rehabilitation inpatients at 2 weeks.

PMID- 25758409
TI  - Factors influencing deprescribing habits among geriatricians.
AB  - BACKGROUND: deprescribing habits among physicians managing older, frailer,
      cognitively impaired patients have not been well investigated. METHODS: an
      anonymised electronic survey was disseminated to all members of an international
      geriatric society/local advanced trainee network (N = 930). This comprised a
      Likert-scale analysis of factors influencing desprescribing, and five case
      vignettes, detailing a patient with progressive cognitive impairment and
      dependency, on a background of ischaemic heart disease and hypertension. RESULTS:
      among 134 respondents (response rate 14.4%), 47.4% were female, 48.9% aged 36-50
      years and 84.1% specialists (15.9% trainees). Respondents commonly rated limited
      life expectancy (96.2%) and cognitive impairment (84.1%) as very/extremely
      important to deprescribing practices. On multivariable analysis, older
      respondents less commonly rated functional dependency (odds ratio [OR] 0.22 per
      change in age category; P < 0.001) and limited life expectancy (OR 0.09, P =
      0.04) important when deprescribing, while female participants (OR 3.03, P <
      0.001) and trainees (versus specialists OR 14.29, P < 0.001) more often rated
      adherence to evidence-based guidelines important. As vignettes described
      increasing dependency and cognitive impairment, physicians were more likely to
      stop donepezil, aspirin, atorvastatin and antihypertensives (all P < 0.001 for
      trend). Aspirin (93.6%) and ramipril (94.1%) were most commonly deprescribed.
      Commonest reasons cited for deprescribing medications were 'dementia severity',
      followed by pill burden. CONCLUSION: in this exploratory analysis, geriatricians
      rated limited life expectancy and cognitive impairment very important in driving
      deprescribing practices. Geriatricians more often deprescribed multiple
      medications in the setting of advancing dependency and cognitive impairment,
      driven by dementia severity and pill burden concerns. Physician characteristics
      also influence deprescribing practices. Further exploration of factors
      influencing deprescribing patterns, and patient outcomes, is needed.

PMID- 25758411
TI  - Effect of microporation on passive and iontophoretic delivery of diclofenac
      sodium.
AB  - Skin pretreatment with a microneedle roller (microporation (MP)) appears a simple
      and inexpensive technique to increase transdermal delivery of topically applied
      drug products. This study investigates the effect of MP on the passive and
      iontophoretic delivery of diclofenac (DCF) by quantifying dermis and plasma
      levels of DCF in a rabbit model. New Zealand albino female rabbits received
      either: (i) a topical application of 4 g of Voltaren(r) 1% gel with or without
      pretreatment with a microroller (0.5 mm needle length; density 23 microneedles
      per cm(2) area) or (ii) a DCF solution (40 mg/2.5 mL) via iontophoresis (IOMED
      transQ(E) medium size patch), with or without microroller pretreatment. A 300
      uA/cm(2) cathodic current was applied for 20 min for a total of 80 mA. DCF
      concentrations were monitored in dermis with microdialysis sampling every 20 min
      for 5 h. Plasma samples were collected over the same period. In the passive
      delivery studies, microroller pretreatment increased Cmax by 1.5- and 2.0-fold in
      skin and plasma, respectively, and AUC by 1.5- and 2.4-fold in skin and plasma,
      respectively. In the iontophoresis delivery studies, microporation increased Cmax
      by 2.0-fold both in skin and in plasma, and AUC by 1.1- and 1.8-fold in skin and
      plasma, respectively. In conclusion, microneedle pretreatment increased
      significantly the systemic exposure of DCF from either passive or iontophoretic
      delivery, whereas the effect in skin was less pronounced. 

PMID- 25758410
TI  - The coelacanth rostral organ is a unique low-resolution electro-detector that
      facilitates the feeding strike.
AB  - The cartilaginous and non-neopterygian bony fishes have an electric sense
      typically comprised of hundreds or thousands of sensory canals distributed in
      broad clusters over the head. This morphology facilitates neural encoding of
      local electric field intensity, orientation, and polarity, used for determining
      the position of nearby prey. The coelacanth rostral organ electric sense,
      however, is unique in having only three paired sensory canals with distribution
      restricted to the dorsal snout, raising questions about its function. To address
      this, we employed magnetic resonance imaging methods to map electrosensory canal
      morphology in the extant coelacanth, Latimeria chalumnae, and a simple dipole
      'rabbit ears' antennae model with toroidal gain function to approximate their
      directional sensitivity. This identified a unique focal region of
      electrosensitivity directly in front of the mouth, and is the first evidence of a
      low-resolution electro-detector that solely facilitates prey ingestion. 

PMID- 25758412
TI  - Development of biofilm-targeted antimicrobial wound dressing for the treatment of
      chronic wound infections.
AB  - It has been established that microbial biofilms are largely responsible for the
      recalcitrance of many wound infections to conventional antibiotics. It was
      proposed that the efficacy of antibiotics could be optimized via the inhibition
      of bacterial biofilm growth in wounds. The combination of antibiofilm agent and
      antibiotics into a wound dressing may be a plausible strategy in wound infection
      management. Xylitol is an antibiofilm agent that has been shown to inhibit the
      biofilm formation. The purpose of this study was to develop an alginate film
      containing xylitol and gentamicin for the treatment of wound infection. Three
      films, i.e. blank alginate film (SA), alginate film with xylitol (F5) and
      alginate film with xylitol and gentamicin (AG), were prepared. The films were
      studied for their physical properties, swelling ratio, moisture absorption,
      moisture vapor transmission rate (MVTR), mechanical and rheology properties, drug
      content uniformity as well as in vitro drug release properties. Antimicrobial and
      antibiofilm in vitro studies on Staphylococcus aureus and Pseudomonas aeruginosa
      were also performed. The results showed that AG demonstrates superior mechanical
      properties, rheological properties and a higher MVTR compared with SA and F5. The
      drug flux of AG was higher than that of commercial gentamicin cream. Furthermore,
      antimicrobial studies showed that AG is effective against both S. aureus and P.
      aeruginosa, and the antibiofilm assays demonstrated that the combination was
      effective against biofilm bacteria. In summary, alginate films containing xylitol
      and gentamicin may potentially be used as new dressings for the treatment of
      wound infection. 

PMID- 25758413
TI  - Untangling the origin of viruses and their impact on cellular evolution.
AB  - The origin and evolution of viruses remain mysterious. Here, we focus on the
      distribution of viral replicons in host organisms, their morphological features,
      and the evolution of highly conserved protein and nucleic acid structures. The
      apparent inability of RNA viral replicons to infect contemporary akaryotic
      species suggests an early origin of RNA viruses and their subsequent loss in
      akaryotes. A census of virion morphotypes reveals that advanced forms were unique
      to viruses infecting a specific supergroup, while simpler forms were observed in
      viruses infecting organisms in all forms of cellular life. Results hint toward an
      ancient origin of viruses from an ancestral virus harboring either filamentous or
      spherical virions. Finally, phylogenetic trees built from protein domain and tRNA
      structures in thousands of genomes suggest that viruses evolved via reductive
      evolution from ancient cells. The analysis presents a complete account of the
      evolutionary history of cells and viruses and identifies viruses as crucial
      agents influencing cellular evolution.

PMID- 25758414
TI  - Effect of the orientation and fluid flow on the accumulation of organotin
      compounds to Chemcatcher passive samplers.
AB  - Monitoring of harmful substances in an aquatic environment is based on spot
      sampling which is the only sampling technique accepted by environmental
      authorities in the European Union. Still the implementation of the European Union
      Water Framework Directive (WFD) requires novel sampling tools for monitoring
      priority pollutants since their concentrations in natural waters can often remain
      below the limit of detection when using the conventional spot sampling method.
      However, this does not necessarily mean that the pollutant is not present in the
      aquatic environment. Many chemicals that are considered to be harmful are
      bioaccumulative and can affect, e.g., reproduction of aquatic organisms even at
      very low concentration levels. Also the timing is crucial since with spot
      sampling the pulse of harmful substances can easily be missed. Passive samplers
      collect the compounds for a certain amount of time which allows the
      concentrations in the sampler to rise to the measurable level where they are easy
      to detect. Organotin compounds (OTCs) have been widely used as plastic
      stabilizers and antifouling agents in ship paints and in many industrial
      processes. Among the OTCs, tributyltin is listed as a WFD priority substance. In
      this study a small-scale flow simulation around the Chemcatcher passive sampler
      was performed to visualize the flow streamlines in the vicinity of the sampler
      and to study the pressure experienced by the receiving phase in different sampler
      positions. With laboratory experiments the sampling rates for each OTC were
      determined and the effect of the flow velocity and sampler orientation on the
      accumulation of OTCs is discussed. The pressure changes were observed on the
      surface of the receiving phase in simulations with varying sampler orientations.
      Despite that, the laboratory experiments discovered no difference in the
      accumulation of compounds when varying the sampler orientation. The
      concentrations of OTCs in the surrounding water calculated from the passive
      sampling results were equivalent to the spot sampling ones. Hence, the
      Chemcatcher passive sampler provides a practical tool for the implementation of
      WFD. 

PMID- 25758415
TI  - 3-(Benzo[d][1,3]dioxol-5-ylamino)-N-(4-fluorophenyl)thiophene-2-carboxamide
      overcomes cancer chemoresistance via inhibition of angiogenesis and P
      glycoprotein efflux pump activity.
AB  - 3-((Quinolin-4-yl)methylamino)-N-(4-(trifluoromethoxy)phenyl)thiophene-2
      carboxamide (OSI-930, 1) is a potent inhibitor of c-kit and VEGFR2, currently
      under phase I clinical trials in patients with advanced solid tumors. In order to
      understand the structure-activity relationship, a series of 3-arylamino N-aryl
      thiophene 2-carboxamides were synthesized by modifications at both quinoline and
      amide domains of the OSI-930 scaffold. All the synthesized compounds were
      screened for in vitro cytotoxicity in a panel of cancer cell lines and for VEGFR1
      and VEGFR2 inhibition. Thiophene 2-carboxamides substituted with
      benzo[d][1,3]dioxol-5-yl and 2,3-dihydrobenzo[b][1,4]dioxin-6-yl groups 1l and 1m
      displayed inhibition of VEGFR1 with IC50 values of 2.5 and 1.9 MUM, respectively.
      Compounds 1l and 1m also inhibited the VEGF-induced HUVEC cell migration,
      indicating its anti-angiogenic activity. OSI-930 along with compounds 1l and 1m
      showed inhibition of P-gp efflux pumps (MDR1, ABCB1) with EC50 values in the
      range of 35-74 MUM. The combination of these compounds with doxorubicin led to
      significant enhancement of the anticancer activity of doxorubicin in human
      colorectal carcinoma LS180 cells, which was evident from the improved IC50 of
      doxorubicin, the increased activity of caspase-3 and the significant reduction in
      colony formation ability of LS180 cells after treatment with doxorubicin.
      Compound 1l showed a 13.8-fold improvement in the IC50 of doxorubicin in LS180
      cells. The ability of these compounds to display dual inhibition of VEGFR and P
      gp efflux pumps demonstrates the promise of this scaffold for its development as
      multi-drug resistance-reversal agents. 

PMID- 25758416
TI  - Prolonged starvation and subsequent recovery of nitrification process in a
      simulated photovoltaic aeration SBR.
AB  - The ability of a new SBR (sequencing batch reactor) based on simulating
      photovoltaic aeration for maintaining nitrification activity under a 25-day
      starvation period was studied. The activity and abundance of ammonia-oxidizing
      bacteria (AOB) and nitrite-oxidizing bacteria (NOB) and the diversity of AOB were
      investigated. The measured biomass decay rates were 0.017 day(-1) and 0.029 day(
      1) for AOB and NOB, respectively. These decay rates correlated well with AOB and
      NOB population quantified by real-time PCR. The recovery of ammonia oxidation
      rate and nitrite oxidation rate needed 4 and 7 days, respectively, indicating
      that NOB was more affected than AOB by starvation conditions. According to the
      real-time PCR results, Nitrospira was the dominant NOB in the reactor.
      Phylogenetic analysis indicated that Nitrosomonas oligotropha cluster was the
      dominant major cluster before and after starvation. Moreover, Pareto-Lorenz
      evenness distribution curves were plotted to interpret the interspecies abundance
      of AOB; the results suggested that AOB community possessed a balanced structure
      with medium Fo (Functional organization). Thus, the community can potentially
      deal with changing environmental conditions (e.g., starvation) and preserve its
      functionality according to the concept of functional redundancy.

PMID- 25758417
TI  - Genotoxic potency of mercuric chloride in gill cells of marine gastropod Planaxis
      sulcatus using comet assay.
AB  - In vivo and in vitro exposures were used to investigate the genotoxicity of
      mercuric chloride (HgCl2) to the marine snail, Planaxis sulcatus. The comet assay
      protocol was validated on gill cells exposed in vitro to hydrogen peroxide (H2O2,
      0-50 MUM). Snails were exposed in vivo for 96 h to HgCl2 (10, 20, 50, and 100
      MUg/l). Our results showed significant concentration-dependent increase in the
      tail DNA (TDNA) and olive tail moment (OTM) in exposed snails for all doses
      compared with controls. In vitro exposure to HgCl2 (10-100 MUg/l) resulted in
      significantly higher values for TDNA at all concentrations. Our results showed
      that DNA damage increased in the gill cell with increasing exposure time. This
      study demonstrates the usefulness of comet assay for detection of DNA damage
      after exposure to HgCl2 and the sensitivity of marine snail P. sulcatus as a good
      candidate species for metal pollution.

PMID- 25758418
TI  - Study of the carbonaceous aerosol and morphological analysis of fine particles
      along with their mixing state in Delhi, India: a case study.
AB  - Because of high emissions of anthropogenic as well as natural particles over the
      Indo-Gangetic Plains (IGP), it is important to study the characteristics of fine
      (PM2.5) and inhalable particles (PM10), including their morphology, physical and
      chemical characteristics, etc., in Delhi during winter 2013. The mean mass
      concentrations of fine (PM2.5) and inhalable (PM10) (continuous) was 117.6 +/-
      79.1 and 191.0 +/- 127.6 MUg m(-3), respectively, whereas the coarse mode (PM10
      2.5) particle PM mass was 73.38 +/- 28.5 MUg m(-3). During the same period,
      offline gravimetric monitoring of PM2.5 was conducted for morphological analysis,
      and its concentration was ~37 % higher compared to the continuous measurement.
      Carbonaceous PM such as organic carbon (OC) and elemental carbon (EC) were
      analyzed on the collected filters, and their mean concentration was respectively
      33.8 and 4.0 MUg m(-3) during the daytime, while at night it was 41.2 and 10.1
      MUg m(-3), respectively. The average OC/EC ratio was 8.97 and 3.96 during the day
      and night, respectively, indicating the formation of secondary organic aerosols
      during daytime. Effective carbon ratio was studied to see the effect of aerosols
      on climate, and its mean value was 0.52 and 1.79 during night and day, indicating
      the dominance of absorbing and scattering types of aerosols respectively into the
      atmosphere over the study region. Elemental analysis of individual particles
      indicates that Si is the most abundant element (~37-90 %), followed by O (oxide)
      and Al. Circularity and aspect ratio was studied, which indicates that particles
      are not perfectly spherical and not elongated in any direction. Trajectory
      analysis indicated that in the months of February and March, air masses appear to
      be transported from the Middle Eastern part along with neighboring countries and
      over Thar Desert region, while in January it was from the northeast direction
      which resulted in high concentrations of fine particles.

PMID- 25758419
TI  - Spatial and temporal variation of total mercury and methylmercury in lacustrine
      wetland in Korea.
AB  - The spatial and temporal variations of total mercury (THg) and methylmercury
      (MeHg) concentrations (n = 120, respectively) in water and sediments of the
      Yangsuri lacustrine wetland in Korea were measured. The average concentrations of
      THg and MeHg in surface water were 2.04 +/- 1.97 and 0.05 +/- 0.05 ng L(-1),
      respectively. The concentrations of THg and MeHg in sediments ranged from 1.28 to
      85.83 and <=0.01 to 0.35 ng g(-1), respectively, and varied depending on the
      location. In the vegetated zone located near residential areas, the highest
      concentrations of THg and MeHg in both surface water and sediments were obtained
      near the residential areas, especially during the fall season. This result might
      be due to increased methylation rate of Hg by water turnover in the fall season.
      While THg and MeHg concentrations in water were not correlated, they were
      significantly correlated in sediment (r = 0.75; P < 0.01). Log-transformed Hg
      concentrations in sediments were highly correlated with log-transformed organic
      matter (OM) and acid volatile sulfide (AVS) concentrations (P < 0.01). We also
      collected five species of fish near the output point of the wetland, and MeHg
      concentrations in fish tissue varied from 21.30 to 154.66 MUg kg(-1) w/w, which
      was significantly dependent on fish species (P < 0.05). This is the first
      reported study which measured the levels of mercury, especially MeHg in the
      wetlands, and freshwater fish species in Korea.

PMID- 25758421
TI  - NaCl alleviates Cd toxicity by changing its chemical forms of accumulation in the
      halophyte Sesuvium portulacastrum.
AB  - It has previously been shown that certain halophytes can grow and produce biomass
      despite of the contamination of their saline biotopes with toxic metals. This
      suggests that these plants are able to cope with both salinity and heavy metal
      constraints. NaCl is well tolerated by halophytes and apparently can modulate
      their responses to Cd. However, the underlying mechanisms remain unclear. This
      study explores the impact of NaCl on growth, Cd accumulation, and Cd speciation
      in tissues of the halophyte Sesuvium portulacastrum. Seedlings of S.
      portulacastrum were exposed during 1 month to 0, 25, and 50 MUM Cd combined with
      low salinity (LS, 0.09 mM NaCl) or high salinity (HS, 200 mM NaCl) levels. Growth
      parameters and total tissue Cd concentrations were determined, in leaves, stems,
      and root. Moreover, Cd speciation in these organs was assessed by specific
      extraction procedures. Results showed that, at LS, Cd induced chlorosis and
      necrosis and drastically reduced plant growth. However, addition of 200 mM NaCl
      to Cd containing medium alleviated significantly Cd toxicity symptoms and
      restored plant growth. NaCl reduced the concentration of Cd in the shoots;
      nevertheless, due to maintenance of higher biomass under HS, the quantity of
      accumulated Cd was not modified. NaCl modified the chemical form of Cd in the
      tissues by increasing the proportion of Cd bound to pectates, proteins, and
      chloride suggesting that this change in speciation is involved in the positive
      impact of NaCl on Cd tolerance. We concluded that the tolerance of S.
      portulacastrum to Cd was enhanced by NaCl. This effect is rather governed by the
      modification of the speciation of the accumulated Cd than by the reduction of Cd
      absorption and translocation.

PMID- 25758420
TI  - Microbial siderophores and their potential applications: a review.
AB  - Siderophores are small organic molecules produced by microorganisms under iron
      limiting conditions which enhance the uptake of iron to the microorganisms. In
      environment, the ferric form of iron is insoluble and inaccessible at
      physiological pH (7.35-7.40). Under this condition, microorganisms synthesize
      siderophores which have high affinity for ferric iron. These ferric iron
      siderophore complexes are then transported to cytosol. In cytosol, the ferric
      iron gets reduced into ferrous iron and becomes accessible to microorganism. In
      recent times, siderophores have drawn much attention due to its potential roles
      in different fields. Siderophores have application in microbial ecology to
      enhance the growth of several unculturable microorganisms and can alter the
      microbial communities. In the field of agriculture, different types of
      siderophores promote the growth of several plant species and increase their yield
      by enhancing the Fe uptake to plants. Siderophores acts as a potential biocontrol
      agent against harmful phyto-pathogens and holds the ability to substitute
      hazardous pesticides. Heavy-metal-contaminated samples can be detoxified by
      applying siderophores, which explicate its role in bioremediation. Siderophores
      can detect the iron content in different environments, exhibiting its role as a
      biosensor. In the medical field, siderophore uses the "Trojan horse strategy" to
      form complexes with antibiotics and helps in the selective delivery of
      antibiotics to the antibiotic-resistant bacteria. Certain iron overload diseases
      for example sickle cell anemia can be treated with the help of siderophores.
      Other medical applications of siderophores include antimalarial activity, removal
      of transuranic elements from the body, and anticancer activity. The aim of this
      review is to discuss the important roles and applications of siderophores in
      different sectors including ecology, agriculture, bioremediation, biosensor, and
      medicine. 

PMID- 25758422
TI  - Acute Vagal Nerve Stimulation Lowers alpha2 Adrenoceptor Availability: Possible
      Mechanism of Therapeutic Action.
AB  - BACKGROUND: Vagal nerve stimulation (VNS) emerged as an anti-epileptic therapy,
      and more recently as a potential antidepressant intervention.
      OBJECTIVE/HYPOTHESIS: We hypothesized that salutary effects of VNS are mediated,
      at least in part, by augmentation of the inhibitory effects of cortical
      monoaminergic neurotransmission at appropriate receptors, specifically
      adrenoceptors. Our objective was to measure the effect of acute VNS on alpha2
      adrenoceptor binding. METHODS: Using positron emission tomography (PET), we
      measured changes in noradrenaline receptor binding associated with acute VNS
      stimulation in six anesthetized Gottingen minipigs. We used the selective alpha2
      adrenoceptor antagonist [11C]yohimbine, previously shown to be sensitive to
      competition from the receptor's endogenous ligands, as a surrogate marker of
      monoamine release. PET records were acquired 4-6 weeks after the implant of a VNS
      electrode in minipigs before and within 30 min of the initiation of 1 mA
      stimulation. Kinetic analysis with the Logan graphical linearization generated
      tracer volumes of distribution for each condition. We used an averaged value of
      the distribution volume of non-displaceable ligand (VND), to calculate binding
      potentials for selected brain regions of each animal. RESULTS: VNS treatment
      markedly reduced the binding potential of yohimbine in limbic, thalamic and
      cortical brain regions, in inverse correlation with the baseline binding
      potential. CONCLUSION: The result is consistent with release of noradrenaline by
      antidepressant therapy, implying a possible explanation for the antidepressant
      effect of VNS.

PMID- 25758423
TI  - Scaffolding the retina: the interstitial extracellular matrix during rat retinal
      development.
AB  - PURPOSE: To examine the expression of interstitial extracellular matrix
      components and their role during retinal development. MATERIAL AND METHODS:
      Fibronectin (FN), collagen IV (Coll IV) and laminin 5 (Lam 5) expression in rat
      retinas from developmental stages E17 to adult were studied. In addition, PN5
      full-thickness retinas were cultured for 7 days with dispase, which selectively
      cleaves FN and Coll IV, at either 0.5 U/ml or 5.0 U/ml for 3 or 24h. Eyecups and
      retinal cultures were examined morphologically using hematoxylin and eosin
      staining and immunohistochemistry. RESULTS: Coll IV, Lam 5 and FN were all
      transiently expressed in the interstitial matrix of the retinal layers during
      development. The retinal layers in dispase treated explants was severely
      disturbed in a dose and time dependent manner. CONCLUSIONS: FN, Lam 5 and Coll
      IV, are present in the interstitial extracellular matrix during rat retinal
      development. Enzymatic cleavage of FN and Coll IV early in the lamination process
      disrupts the retinal layers implicating their pivotal role in this process.

PMID- 25758424
TI  - microRNA-107 functions as a candidate tumor suppressor gene in renal clear cell
      carcinoma involving multiple genes.
AB  - BACKGROUND: MicroRNAs (miRNAs) are small RNAs with oncogenic and tumor
      suppressing functions in cancer. miRNAs not only regulate various target genes
      but also participate in vital signaling pathways. METHODS AND RESULTS: The tumor
      suppressing function of miRNA-107 (miR-107) was confirmed in clear cell renal
      cell carcinoma in 52 paired clinical specimens and renal cell carcinoma cell
      lines. Significant correlations were noted between clinical features and miR-107
      expression level. Lentiviral vector and biosynthesis mimics were used to
      overexpress pre-miR-107 or mimicked miR-107 to investigate further the
      tumorigenesis of miR-107 in vivo and in vitro. Cell proliferation and
      invasiveness were inhibited in the 786-O cell line after miR-107 was delivered.
      High miR-107 level expression can apparently induce cell cycle arrest at the G2/M
      phase and retard tumor growth in nude mice. In addition, eukaryotic translation
      initiation factor 5 was found to be a direct target of miR-107 and exhibited an
      inverse relationship with miR-107. It was seen that p53 and VHL genes, which are
      implicated in renal tumors, were associated with miR-107. CONCLUSION: In summary,
      our results showed that miR-107 can inhibit cell proliferation and invasiveness
      of renal cell carcinoma. Furthermore, this study may provide a potential
      therapeutic regimen for clear cell renal cell carcinoma treatment.

PMID- 25758425
TI  - Validation of a Parent Report Questionnaire: The Infant Gastrointestinal Symptom
      Questionnaire.
AB  - OBJECTIVE: To evaluate the reliability and validity of the Infant
      Gastrointestinal Symptom Questionnaire (IGSQ), a tool to assess feeding tolerance
      in infants. METHODS: Qualitative methods were used to develop IGSQ content across
      5 symptom clusters, yielding a 13-item index of parent-reported infant digestion
      and elimination behaviors over the prior 7 days. Classical psychometric methods
      evaluated factor structure, interrater and retest reliability, and validity in 4
      prospective studies of 836 infants. RESULTS: Interrater and retest reliability
      were acceptable to good. IGSQ Index score was highly correlated (r = 0.89) with
      daily parent reports. IGSQ scores were significantly different between infants
      whose parents planned to switch formulas because of perceived feeding problems
      and those without parental concerns. CONCLUSIONS: The IGSQ is a practical,
      reliable, and valid method for assessment of infant gastrointestinal-related
      behaviors. Its use in clinical studies can provide empirical evidence to advance
      parent education regarding both normal and clinically meaningful feeding-related
      behaviors.

PMID- 25758426
TI  - Growth and Tolerance of Term Infants Fed Formula With Probiotic Lactobacillus
      reuteri.
AB  - BACKGROUND: Lactobacillus reuteri has been studied for its safety and beneficial
      effects in infants. This study assessed growth of infants fed a partially
      hydrolyzed whey formula with L reuteri. METHODS: Healthy term infants were
      randomized to 1 of 2 formulas (partially hydrolyzed whey formula with (PRO) or
      without (CON) L reuteri from 14 to 112 days of age. Anthropometric measures were
      assessed at 14, 28, 56, 84, and 112 days of age. Tolerance records were completed
      2 days prior to each visit. RESULTS: A total of 122 subjects completed study per
      protocol (60 PRO, 62 CON). No differences were seen in daily weight gain, length,
      or head circumference. Overall, between groups, there were no significant
      differences in formula intake, stool frequency, color, consistency, flatulence,
      frequency of spit-up/vomiting, mood, sleep, or incidence of adverse events.
      CONCLUSION: Infants fed probiotic formula had similar growth to infants fed
      control formula. Both formulas were well tolerated.

PMID- 25758427
TI  - Soy Isoflavone Glycitin (4'-Hydroxy-6-Methoxyisoflavone-7-D-Glucoside) Promotes
      Human Dermal Fibroblast Cell Proliferation and Migration via TGF-beta Signaling.
AB  - Glycitin is a soy isoflavone that exhibits antioxidant, antiallergic, and anti
      osteoporosis activities. We investigated the effects of glycitin on dermal
      fibroblast proliferation and migration. Treatment of primary dermal fibroblasts
      with glycitin increased cell proliferation and migration. In addition, treatment
      with 20 MUM glycitin for 24 h induced the synthesis of collagen type I and type
      III at both the mRNA and protein levels. Fibronectin was also increased by 20%
      after treatment. Matrix metalloproteinase-1 collagenase was decreased in the
      media after 24-h incubation with glycitin, and the synthesis of transforming
      growth factor-beta (TGF-beta) mRNA increased approximately twofold in cells
      following glycitin treatment. Phosphorylation of Smad2 and Smad3 increased after
      1 h of glycitin treatment, and phosphorylation continued for 24 h. Furthermore,
      the phosphorylated form of AKT was increased in glycitin-treated cells after 3 h
      and remained higher for 24 h. Thus, glycitin treatment produces anti-aging
      effects including increased total collagen in the culture media, decreased
      elastase, and decreased beta-galactosidase. Together, these results indicate that
      glycitin stimulates TGF-beta secretion, and the subsequent autocrine actions of
      TGF-beta induce proliferation of fibroblasts, ultimately protecting skin cells
      from aging and wrinkling.

PMID- 25758428
TI  - The application of cultured epithelial autografts improves survival in burns.
AB  - This prospective observational study was performed to analyze the clinical
      outcomes of patients with massive burns treated using cultured epithelial
      autografts (CEAs) and to determine the association of this treatment with
      survival outcomes. During 2006-2013, total 177 massive-burns subjects treated
      with (96 subjects) or without (81 subjects) CEAs. Data were analyzed using the
      independent t test or chi-square test. Multivariate logistic regression, Kaplan
      Meier survival, and Cox regression analyses were performed to evaluate the
      factors that influenced mortality. Age, percentage of total body surface area
      burned, incidence of inhalation injury, allograft-application rate, Abbreviated
      Burn Severity Index score, length of hospital stay, and mortality significantly
      differed between the CEA and noncultured epithelial autograft groups. Mortality
      and other clinical parameters did not differ between the sheet-type and spray
      type CEA groups. Allograft application (odds ratio, 4.44; p < 0.01) significantly
      influenced CEA application. The CEA group showed significantly higher survival
      rates (p = 0.05). Cultured epithelial autografting had a hazard ratio of 0.55 (p
      = 0.02) and 0.59 (p = 0.05) according to the uni- and multivariate Cox regression
      analysis, respectively. In conclusion, early and aggressive allograft application
      is required to facilitate CEA application. Furthermore, the use of CEAs was
      associated with a lower mortality, but this result should be interpreted with
      caution as the groups were not randomized.

PMID- 25758430
TI  - Hypercysteinemia hypes up the inflammasome.

PMID- 25758429
TI  - Impaired calcium-calmodulin-dependent inactivation of Cav1.2 contributes to loss
      of sarcoplasmic reticulum calcium release refractoriness in mice lacking
      calsequestrin 2.
AB  - AIMS: In cardiac muscle, Ca(2+) release from sarcoplasmic reticulum (SR) is
      reduced with successively shorter coupling intervals of premature stimuli, a
      phenomenon known as SR Ca(2+) release refractoriness. We recently reported that
      the SR luminal Ca(2+) binding protein calsequestrin 2 (Casq2) contributes to
      release refractoriness in intact mouse hearts, but the underlying mechanisms
      remain unclear. Here, we further investigate the mechanisms responsible for
      physiological release refractoriness. METHODS AND RESULTS: Gene-targeted ablation
      of Casq2 (Casq2 KO) abolished SR Ca(2+) release refractoriness in isolated mouse
      ventricular myocytes. Surprisingly, impaired Ca(2+)-dependent inactivation of L
      type Ca(2+) current (ICa), which is responsible for triggering SR Ca(2+) release,
      significantly contributed to loss of Ca(2+) release refractoriness in Casq2 KO
      myocytes. Recovery from Ca(2+)-dependent inactivation of ICa was significantly
      accelerated in Casq2 KO compared to wild-type (WT) myocytes. In contrast, voltage
      dependent inactivation measured by using Ba(2+) as charge carrier was not
      significantly different between WT and Casq2 KO myocytes. Ca(2+)-dependent
      inactivation of ICa was normalized by intracellular dialysis of excess apo-CaM
      (20 MUM), which also partially restored physiological Ca(2+) release
      refractoriness in Casq2 KO myocytes. CONCLUSIONS: Our findings reveal that the
      intra-SR protein Casq2 is largely responsible for the phenomenon of SR Ca(2+)
      release refractoriness in murine ventricular myocytes. We also report a novel
      mechanism of impaired Ca(2+)-CaM-dependent inactivation of Cav1.2, which
      contributes to the loss of SR Ca(2+) release refractoriness in the Casq2 KO mouse
      model and, therefore, may further increase risk for ventricular arrhythmia in
      vivo.

PMID- 25758432
TI  - Going the distance: Epigenetic regulation of endothelial endothelin-1 controls
      cardiac hypertrophy.

PMID- 25758431
TI  - EGFR inhibition protects cardiac damage and remodeling through attenuating
      oxidative stress in STZ-induced diabetic mouse model.
AB  - Diabetes mellitus is strongly associated with cardiomyopathy. The underlying
      mechanisms for the development of diabetic cardiomyopathy are complex and not
      completely understood. Recent studies showed that epidermal growth factor
      receptors (EGFRs) are involved in diabetes-induced cardiac injury. However, the
      role of EGFR in the diabetic heart has yet to be confirmed. The aim of the
      present study is to further determine the role of EGRF in the pathogenesis of
      diabetic heart injury. The type 1 diabetic mice induced by streptozotocin were
      treated with EGFR inhibitors (AG1478 and 451) for 8 weeks, respectively. It was
      observed that diabetes induced phospohorylation of EGFR and AKT, increased
      cardiac ROS levels, and ultimately led to cardiac remodeling including cardiac
      hypertrophy, disorganization, apoptosis, and fibrosis, while all these molecular
      and pathological alterations were attenuated by the treatment with EGFR
      inhibitors. In vitro, either pharmacological inhibition of EGFR/AKT or sh-RNA
      silencing of EGFR significantly inhibited high concentration glucose (HG)-induced
      ROS generation and subsequently cell apoptosis in both cardiac H9C2 cells and
      primary rat cardiomyocytes, respectively. The ROS reduction by EGFR inhibitor was
      associated with the decreased NADPH oxidase activity and expression in H9c2
      cells. HG-induced cardiomyocyte injuries were also reduced by NAC, an inhibitor
      of ROS. This study provides evidence that EGFR has a key role in the pathogenesis
      of STZ-induced diabetic cardiac damage and remodeling via ROS generation, and
      suggests that EGFR may be a potential target in treating diabetic cardiomyopathy.

PMID- 25758433
TI  - Favourable renal survival in paediatric microscopic polyangiitis: efficacy of a
      novel treatment algorithm.
AB  - BACKGROUND: Microscopic polyangiitis (MPA) is one of the most common forms of
      antineutrophil cytoplasm autoantibodies (ANCA)-associated vasculitis in children.
      Cyclophospamide and glucocorticoid-based treatment protocols are still considered
      gold standard in managing this multi-system disorder. But treatment-related
      toxicity is a major cause of chronic morbidity and early mortality in MPA. Hence,
      the search for an effective and safe alternative immunosuppressant is essential.
      METHODS: A retrospective analysis of baseline clinico-pathological presentation
      and treatment-outcome was performed among 11 paediatric MPA patients. All of whom
      were treated with a pre-specified cyclophosphamide free, rituximab- and
      mycophenolate mofetil (MMF)-based management protocol as per centre practice.
      RESULTS: We describe the clinical course of 11 children with MPA over a median
      follow-up period of 20.9 months. Both patient survival and renal survival at 1
      year follow-up were 100%. In spite of the varying degree of renal involvement at
      presentation, kidney function was recovered in all patients with a median
      estimated glomerular filtration rate (eGFR) of 79.5 mL/min/1.73 m(2). At last
      follow-up, 91% (10/11) of patients were in complete remission and one (9%) child
      continued partial remission state. There was no treatment failure. In total, 73%
      (8/11) of patients were off steroids at last follow-up and 82% (9/11) of patients
      never relapsed during follow-up period. CONCLUSIONS: Efficacy and medium-term
      safety of rituximab- and MMF-based protocol in managing children with MPA was
      evident in this study.

PMID- 25758434
TI  - Familial C3 glomerulonephritis associated with mutations in the gene for
      complement factor B.
AB  - We report the first case of familial C3 glomerulonephritis (C3GN) associated with
      mutations in the gene for complement factor B (CFB). A 12-year-old girl was
      diagnosed with biopsy-proven C3GN. Her mother had a history of treatment for
      membranoproliferative glomerulonephritis, and her brother had hypocomplementemia
      without urinary abnormalities. DNA analysis revealed heterozygosity for CFB
      p.S367R in the patient, mother and brother. Evaluation of the structure-function
      relationship supports that this mutation has gain-of-function effects in CFB. The
      present case suggests that CFB has an important role in the etiology of C3GN and
      provides a new insight into anticomplement therapy approaches. 

PMID- 25758435
TI  - Ultrasound: the versatile energy source.

PMID- 25758436
TI  - Ultrasound guided high intensity focused ultrasound (USgHIFU) ablation for
      uterine fibroids: Do we need the microbubbles?
AB  - PURPOSE: The aim of this study was to assess the safety and effectiveness of
      contrast-enhanced ultrasound (CEUS) on ultrasound guided high intensity focused
      ultrasound (USgHIFU) ablation of uterine fibroids. METHODS: Thirty-three patients
      (37 fibroids) were randomly assigned to two groups: group A (17 patients, 20
      fibroids) in which CEUS was used before, during and after HIFU treatment, and
      group B (16 patients, 17 fibroids) in which CEUS was not administered at all.
      Follow-up including contrast-enhanced magnetic resonance imaging (MRI) and a
      clinical questionnaire was performed, and technical success, ablation efficacy,
      volume reduction and complications were assessed. RESULTS: Technical success was
      100% in both groups. CEUS revealed residual enhancement in 40% of the patients in
      group A and the treatment was continued until the completion of ablation. MRI at
      1 month after treatment revealed significant difference in the relative fibroid
      volume reduction rate between the two groups: 16.1% in group A versus 4.8%, in
      group B (p = 0.01). There was no statistically significant relative volume
      reduction rate for the results at 3, 6 and 12 months and no significant changes
      in the quality of life results or the complication rate. CONCLUSIONS: CEUS was
      safe and effective in enhancing US guidance during HIFU ablation of uterine
      fibroids. Moreover, the use of CEUS during HIFU sonication increased the ablation
      efficacy, leading to a more relevant fibroid volume reduction at 1 and 3 months.
      This gap disappeared after 6 months, when there were no differences between the
      two groups of patients at MRI. However, in our experience, USgHIFU represented a
      very effective method for the treatment of uterine fibroids, and the use of CEUS
      during HIFU procedure reduced the treatment time and treatment repetitions for
      incomplete fibroid ablation.

PMID- 25758437
TI  - Toward air-stable multilayer phosphorene thin-films and transistors.
AB  - Few-layer black phosphorus (BP), also known as phosphorene, is poised to be the
      most attractive graphene analogue owing to its high mobility approaching that of
      graphene, and its thickness-tunable band gap that can be as large as that of
      molybdenum disulfide. In essence, phosphorene represents the much sought after
      high-mobility, large direct band gap two-dimensional layered crystal that is
      ideal for optoelectronics and flexible devices. However, its instability in air
      is of paramount concern for practical applications. Here, we demonstrate air
      stable BP devices with dielectric and hydrophobic encapsulation. Microscopy,
      spectroscopy, and transport techniques were employed to elucidate the aging
      mechanism, which can initiate from the BP surface for bare samples, or edges for
      samples with thin dielectric coating, highlighting the ineffectiveness of
      conventional scaled dielectrics. Our months-long studies indicate that a double
      layer capping of Al2O3 and hydrophobic fluoropolymer affords BP devices and
      transistors with indefinite air-stability for the first time, overcoming a
      critical material challenge for applied research and development. 

PMID- 25758438
TI  - Understanding the needs of vulnerable prisoners: the role of social and emotional
      wellbeing.
AB  - PURPOSE: Social and emotional wellbeing (SEWB) is a term used to refer to the
      state of an individual's overall wellbeing. This review aims to consider the
      importance of understanding and assessing SEWB in prisoner populations, and
      identify potentially important differences between groups of prisoners, including
      those who identify as from minority cultural backgrounds (Aboriginal and Torres
      Strait Islander in Australia), protective custody prisoners, remand prisoners,
      prisoners identified with an intellectual disability, and prisoners with an
      acquired brain injury. DESIGN/METHODOLOGY/APPROACH: The paper is a general review
      of the published literature, with a specific focus on work conducted with
      Aboriginal and Torres Strait Islander communities in Australia. FINDINGS: Eight
      domains of SEWB are identified across which Aboriginal and Torres Strait Islander
      prisoners, along with those in protection units, remandees, and prisoners with
      intellectual disabilities or acquired brain injuries are likely to experience
      particularly low levels of functioning. Few programs have been developed to
      address these needs, although attending to low levels of SEWB has the potential
      to make a positive contribution to prisoner health, prison management, and
      offender rehabilitation. ORIGINALITY/VALUE: Relatively little literature has
      considered this topic previously and, as a result, the paper is necessarily
      descriptive. Nonetheless, issues of SEWB appear to warrant further consideration,
      particularly in relation to those prisoners who identify with minority cultural
      groups.

PMID- 25758439
TI  - Exploring motivations to stop injecting in English prisons: qualitative research
      with former male prisoners.
AB  - PURPOSE: This paper aims to explore the cessation of injecting amongst male drug
      users when in prison in England and uncovers what influenced this behaviour and
      why. DESIGN/METHODOLOGY/APPROACH: Qualitative interviews were conducted with 30
      male drug users on release from prison to explore what happened to their
      injecting drug use in prison. The research was conducted from a pragmatic harm
      reduction approach using grounded theory. FINDINGS: Not injecting in prison was
      identified as a pertinent finding and nine overarching themes accounted for this
      decline. The themes often overlapped with one another, highlighting how the
      decision not to inject when last in prison was multi-factorial. Running
      throughout the themes were participants' concerns regarding the health and social
      risks attributed to injecting in prison, alongside an appreciation of some of the
      rehabilitative measures and opportunities offered to injecting drug users when in
      prison. ORIGINALITY/VALUE: This qualitative research offers an updated
      perspective on illicit drug injecting in prison in England from the view of drug
      users since health and prison policy changes in prescribing and practice. It
      contributes to evidence suggesting that prisons can be used as a time of reprieve
      and recovery from injecting drug use.

PMID- 25758440
TI  - Access to harm reduction and HIV-related treatment services inside Indian
      prisons: experiences of formerly incarcerated injecting drug users.
AB  - PURPOSE: The authors aimed to examine the incarceration experiences of injecting
      drug users in accessing harm reduction, and HIV-related services inside prisons
      in India. DESIGN/METHODOLOGY/APPROACH: The authors conducted three focus groups
      with a purposive sample of 23 formerly incarcerated male IDUs and four key
      informant interviews with a former police official, a drug dealer and service
      providers. Data were analyzed using a constant comparative method. FINDINGS:
      Participants reported availability of alcohol and injectable or oral drugs such
      as heroin, dextropropoxyphene, and marijuana inside prisons. Inmates obtained
      drugs and clean syringes (one syringe bought for 2.5-4 USD) through prison staff,
      and collected used syringes and needles from the dustbins in prison sickrooms.
      Needles and syringes were reused and shared. Prisons did not have needle and
      syringe programmes, detoxification, overdose management or opioid substitution
      treatment. Drug-using prison inmates faced several challenges in accessing
      antiretroviral treatment and HIV testing. PRACTICAL IMPLICATIONS: The authors'
      findings emphasize the need to protect the health of injection drug-using inmates
      by introducing harm reduction programmes and removing barriers to HIV testing and
      antiretroviral treatment. ORIGINALITY/VALUE: This study illustrates, for the
      first time, the contexts behind high risk injecting drug use behaviours among
      prison inmates in India. It also highlights the lack of availability of harm
      reduction services such as needle and syringe programmes, drug detoxification and
      opioid substitution treatment inside prisons. Further, it demonstrates the
      difficulties faced by HIV-positive prison inmates in getting timely and
      uninterrupted antiretroviral treatment.

PMID- 25758441
TI  - HIV-related knowledge and attitudes among Indonesian prison officers.
AB  - PURPOSE: Prison officers have a vital role in running a secure and healthy living
      environment for the inmates. The purpose of this article is to examine the
      relationship between HIV/AIDS-related knowledge and attitude towards inmates
      living with HIV among the officers in an Indonesian narcotics prison.
      DESIGN/METHODOLOGY/APPROACH: A total of 93 officers from a narcotics prison in
      Bandung, Indonesia voluntarily participated in this cross-sectional study by
      completing a self-reported questionnaire. A Prior focus group discussion was also
      held among selected participants. FINDINGS: Statistical data analyses indicate
      that all domains of HIV/AIDS-related knowledge, i.e. knowledge of HIV
      transmission, general HIV/AIDS knowledge and knowledge of HIV-prevention, have
      substantial positive correlations with the prison officers' attitude towards
      inmates living with HIV. These results show that the more knowledgeable the
      officers are, the less likely they are to respond in an unfavourable manner to
      inmates living with HIV and vice versa. RESEARCH LIMITATIONS/IMPLICATIONS:
      Despite the limited participants involved in this study, the knowledge gaps that
      are identified in this study should be the starting point for the development of
      educational interventions for prison officers. PRACTICAL IMPLICATIONS: Sufficient
      educational programs and the latest materials need to be made available within
      the prison. SOCIAL IMPLICATIONS: Commitment from prison authorities as well as a
      proper policy are also needed. ORIGINALITY/VALUE: This study helped prison
      authorities to identify areas for knowledge development of the officers.
      Hopefully the positive attitude towards inmates living with HIV will be
      developed.

PMID- 25758442
TI  - Interventions to improve cultural competency in health care for Indigenous
      peoples of Australia, New Zealand, Canada and the USA: a systematic review.
AB  - PURPOSE: This article describes the characteristics and reviews the
      methodological quality of interventions designed to improve cultural competency
      in health care for Indigenous peoples of Australia, New Zealand, Canada and the
      USA. DATA SOURCES: A total of 17 electronic databases and 13 websites for the
      period of 2002-13. STUDY SELECTION: Studies were included if they evaluated an
      intervention strategy designed to improve cultural competency in health care for
      Indigenous peoples of Australia, New Zealand, the USA or Canada. DATA EXTRACTION:
      Information on the characteristics and methodological quality of included studies
      was extracted using standardized assessment tools. RESULTS OF DATA SYNTHESIS:
      Sixteen published evaluations of interventions to improve cultural competency in
      health care for Indigenous peoples were identified: 11 for Indigenous peoples of
      the USA and 5 for Indigenous Australians. The main types of intervention
      strategies were education and training of the health workforce, culturally
      specific health programs and recruitment of an Indigenous health workforce. Main
      positive outcomes reported were improvements in health professionals' confidence,
      and patients' satisfaction with and access to health care. The methodological
      quality of evaluations and the reporting of key methodological criteria were
      variable. Particular problems included weak study designs, low or no reporting of
      consent rates, confounding and non-validated measurement instruments. CONCLUSION:
      There is a lack of evidence from rigorous evaluations on the effectiveness of
      interventions for improving cultural competency in health care for Indigenous
      peoples. Future evaluations should employ more rigorous study designs and extend
      their measurement of outcomes beyond those relating to health professionals, to
      those relating to the health of Indigenous peoples.

PMID- 25758443
TI  - Towards actionable international comparisons of health system performance: expert
      revision of the OECD framework and quality indicators.
AB  - OBJECTIVE: To review and update the conceptual framework, indicator content and
      research priorities of the Organisation for Economic Cooperation and
      Development's (OECD) Health Care Quality Indicators (HCQI) project, after a
      decade of collaborative work. DESIGN: A structured assessment was carried out
      using a modified Delphi approach, followed by a consensus meeting, to assess the
      suite of HCQI for international comparisons, agree on revisions to the original
      framework and set priorities for research and development. SETTING: International
      group of countries participating to OECD projects. PARTICIPANTS: Members of the
      OECD HCQI expert group. RESULTS: A reference matrix, based on a revised
      performance framework, was used to map and assess all seventy HCQI routinely
      calculated by the OECD expert group. A total of 21 indicators were agreed to be
      excluded, due to the following concerns: (i) relevance, (ii) international
      comparability, particularly where heterogeneous coding practices might induce
      bias, (iii) feasibility, when the number of countries able to report was limited
      and the added value did not justify sustained effort and (iv) actionability, for
      indicators that were unlikely to improve on the basis of targeted policy
      interventions. CONCLUSIONS: The revised OECD framework for HCQI represents a new
      milestone of a long-standing international collaboration among a group of
      countries committed to building common ground for performance measurement. The
      expert group believes that the continuation of this work is paramount to provide
      decision makers with a validated toolbox to directly act on quality improvement
      strategies.

PMID- 25758444
TI  - Comparative genome and transcriptome analyses of the social amoeba Acytostelium
      subglobosum that accomplishes multicellular development without germ-soma
      differentiation.
AB  - BACKGROUND: Social amoebae are lower eukaryotes that inhabit the soil. They are
      characterized by the construction of a starvation-induced multicellular fruiting
      body with a spore ball and supportive stalk. In most species, the stalk is filled
      with motile stalk cells, as represented by the model organism Dictyostelium
      discoideum, whose developmental mechanisms have been well characterized. However,
      in the genus Acytostelium, the stalk is acellular and all aggregated cells become
      spores. Phylogenetic analyses have shown that it is not an ancestral genus but
      has lost the ability to undergo cell differentiation. RESULTS: We performed
      genome and transcriptome analyses of Acytostelium subglobosum and compared our
      findings to other available dictyostelid genome data. Although A. subglobosum
      adopts a qualitatively different developmental program from other dictyostelids,
      its gene repertoire was largely conserved. Yet, families of polyketide synthase
      and extracellular matrix proteins have not expanded and a serine protease and ABC
      transporter B family gene, tagA, and a few other developmental genes are missing
      in the A. subglobosum lineage. Temporal gene expression patterns are
      astonishingly dissimilar from those of D. discoideum, and only a limited fraction
      of the ortholog pairs shared the same expression patterns, so that some signaling
      cascades for development seem to be disabled in A. subglobosum. CONCLUSIONS: The
      absence of the ability to undergo cell differentiation in Acytostelium is
      accompanied by a small change in coding potential and extensive alterations in
      gene expression patterns.

PMID- 25758445
TI  - Molecular evidence shows that the liver fluke Fasciola gigantica is the
      predominant Fasciola species in ruminants from Pakistan.
AB  - Fascioliasis is an important disease affecting livestock, with great costs to
      producers worldwide. It has also become a serious issue for human populations in
      some endemic areas as an emerging zoonotic infection. There are two Fasciola
      species of liver fluke responsible for this disease, which occur worldwide,
      Fasciola hepatica and Fasciola gigantica. Identifying these two species on the
      basis of adult or egg morphology requires specialist knowledge due to the
      similarity of characters, and may misidentify putative intermediate or hybrid
      forms. In this study we sequenced the internal transcribed spacer 2 (ITS-2) rDNA
      of liver flukes collected from multiple species of hosts from seven localities in
      the Punjab and Baluchistan provinces of Pakistan, to determine the distribution
      of these two species. All 46 flukes processed in this study, collected from seven
      sites, showed the rDNA ITS-2 genotype corresponding to F. gigantica,
      contradicting previous reports, based on adult and egg morphology, that both
      species are present in Pakistan, with F. hepatica being the more common. 

PMID- 25758446
TI  - Barriers to physician adherence to evidence-based monitoring guidelines in
      chronic myelogenous leukemia.
AB  - PURPOSE: Although monitoring of cytogenetic/molecular responses to therapy in
      chronic myelogenous leukemia (CML) facilitates superior outcomes, less than one
      half of CML patients are monitored using published evidence-based guidelines.
      Barriers to physician adherence with guidelines are unknown. METHODS: An
      anonymous survey was mailed to 515 hematologist-oncologists in New Jersey and
      Indiana exploring attitudes toward monitoring guidelines. RESULTS: Ninety-six
      physicians (19%) responded-89% in community practice, 83% with more than 10 years
      of experience, and 92% caring for CML patients. Eighty-four percent self-reported
      using CML monitoring guidelines, 14% were familiar with but did not adopt
      guidelines and 2% were unfamiliar. Eighty-four percent performed molecular
      monitoring quarterly as recommended; 6% did not perform molecular monitoring at
      all during the first year. Guidelines were considered evidence based by 98%, but
      only 54% strongly considered them easy to find; only 51% strongly felt they
      addressed all aspects of disease management. Patient resource barriers were a
      significant deterrent toward implementation with 30% citing high costs. Physician
      resources, including lack of time to search guidelines, limited use in one fifth.
      Despite 90% believing an online database helpful, between one third and one half
      did not feel that additional training, professional society endorsements, or
      availability of expert consultations would encourage use. CONCLUSIONS:
      Significant barriers to adherence with evidence-based CML guidelines exist.
      Resource barriers, lack of familiarity and lack of agreement restrict adoption,
      but efforts to facilitate use are not desired. Multifaceted educational
      strategies, including automated computerized reminders at point of care, are
      needed to improve quality outcomes in CML.

PMID- 25758447
TI  - Supporting commission on cancer-mandated psychosocial distress screening with
      implementation strategies.
AB  - PURPOSE: The American College of Surgeons Commission on Cancer (CoC) has set
      psychosocial distress screening as a new patient care standard to be met by 2015.
      The standard requires CoC-accredited cancer centers to integrate and monitor
      distress screening and, when needed, refer patients to psychosocial health care
      services. We describe the uptake of distress screening reported by applicants to
      a distress screening cancer education program and the degree of and barriers to
      implementation of distress screening programs reported by selected participants.
      MATERIALS AND METHODS: This cross-sectional study collected quantitative data
      online from applicants to the program between August 1 and November 15, 2013,
      described by frequencies, percentages, and measures of central tendency, and
      qualitative data in person from accepted participants on February 13, 2014,
      analyzed using an integrated approach to open-ended data. RESULTS: Applications
      were received from 70 institutions, 29 of which had started distress screening.
      Seven of 18 selected applicant institutions had not begun screening patients for
      distress. Analysis of qualitative data showed that all participants needed to
      create buy-in among key cancer center staff, including oncologists; to decide how
      to conduct screening in their institution in a way that complied with the
      standard; and to pilot test screening before large-scale rollout. CONCLUSION:
      Fourteen months before the compliance deadline, fewer than half of applicant
      institutions had begun distress screening. Adding implementation strategies to
      mandated quality care standards may reduce uncertainty about how to comply.
      Support from key staff members such as oncologists may increase uptake of
      distress screening.

PMID- 25758448
TI  - Randomized Controlled Trial of Shared Care for Patients With Cancer Involving
      General Practitioners and Cancer Specialists.
AB  - PURPOSE: We aimed to determine whether a shared care model (SCM) during
      chemotherapy treatment improved emotional well-being, empowerment, and prevalence
      of symptoms for people being treated for cancer. METHODS: People receiving
      chemotherapy for hematologic, breast, ovarian, or colorectal malignancies at two
      cancer centers were randomly assigned to receive SCM or standard care. The SCM
      involved a patient-held record, a project coordinator, routine contact between
      the patient and general practitioner/primary care physician, and primary care
      physician education. Participants completed the Hospital Anxiety and Depression
      Scale, the Mini-Mental Adjustment to Cancer, and an empowerment questionnaire
      before, in the middle of, and on completion of chemotherapy. The presence and
      severity of adverse effects of chemotherapy were recorded by patients in a
      symptom diary. RESULTS: Ninety-seven eligible participants were randomly
      allocated, less than half the intended recruitment. There were no significant
      differences between the groups for empowerment, symptom prevalence, or Mini
      Mental Adjustment to Cancer scores. The proportion with clinical anxiety
      (Hospital Anxiety and Depression Scale anxiety score of >= 11) decreased over
      time in both groups (P = .013) but decreased more in the intervention group (P =
      .002). Depression was unchanged over time. CONCLUSION: Our study was limited by
      low recruitment and predominance of patients with breast cancer, and was
      underpowered for the main analyses. Results should therefore be interpreted with
      caution. Little benefit was seen for SCM in the majority of domains including
      empowerment, symptom prevalence, and psychological adjustment to cancer. The SCM
      showed efficacy in clinically anxious patients. Such interventions may be better
      implemented by using a targeted approach to identify at-need subgroups.

PMID- 25758449
TI  - Priorities for quality care in pediatric oncology supportive care.

PMID- 25758450
TI  - Improving documentation of oral chemotherapy at a community cancer center.
AB  - PURPOSE: Safe administration of oral chemotherapy is a complex process that
      represents a potential threat to patient safety. Clear documentation of the plan
      of care for patients receiving oral chemotherapy can improve patient safety by
      ensuring complete health information is available to the health care team.
      METHODS: We undertook a rapid-cycle improvement project to improve documentation
      of oral chemotherapy by increasing the number of components of an oral
      chemotherapy care plan (as outlined by American Society of Clinical Oncology and
      Oncology Nursing Society) documented in the medical record before starting a new
      oral chemotherapy drug. Three improvement cycles were implemented, including:
      introduction of a standardized nursing flow sheet, use of computerized physician
      order entry for oral chemotherapy prescribing, and a review of computerized
      physician order entry to ensure all oral chemotherapy regimens were included.
      RESULTS: Our intervention resulted in a meaningful and sustained improvement in
      the number of components of oral chemotherapy care plans documented in the
      medical record, from a mean of 67% (eight of 12 components) to a mean of 92% (11
      of 12). CONCLUSION: We are hopeful that this improvement project will enhance
      patient safety by improving communication within the health care team regarding
      the details of the chemotherapy care plan.

PMID- 25758452
TI  - Standard duplex criteria overestimate the degree of stenosis after eversion
      carotid endarterectomy.
AB  - OBJECTIVE: The eversion technique for carotid endarterectomy (eCEA) offers an
      alternative to longitudinal arteriotomy and patch closure (pCEA) for open carotid
      revascularization. In some reports, eCEA has been associated with a higher rate
      of >50% restenosis of the internal carotid when it is defined as peak systolic
      velocity (PSV) >125 cm/s by duplex imaging. Because the conformation of the
      carotid bifurcation may differ after eCEA compared with native carotid arteries,
      it was hypothesized that standard duplex criteria might not accurately reflect
      the presence of restenosis after eCEA. METHODS: In a case-control study, the
      outcomes of all patients undergoing carotid endarterectomy by one surgeon during
      the last 10 years were analyzed retrospectively, with a primary end point of PSV
      >125 cm/s. Duplex flow velocities were compared with luminal diameter
      measurements for any carotid computed tomography arteriography or magnetic
      resonance angiography study obtained within 2 months of duplex imaging, with the
      degree of stenosis calculated by the methodology used in the North American
      Symptomatic Carotid Endarterectomy Trial (NASCET) and the European Carotid
      Surgery Trial (ECST) as well as cross-sectional area (CSA) reduction. Simulations
      were generated and analyzed by computational model simulations of the eCEA and
      pCEA arteries. RESULTS: Eversion and longitudinal arteriotomy with patch
      techniques were used in 118 and 177 carotid arteries, respectively. Duplex follow
      up was available in 90 eCEA arteries at a median of 16 (range, 2-136) months and
      in 150 pCEA arteries at a median of 41 (range, 3-115) months postoperatively. PSV
      >125 cm/s was present at some time during follow-up in 31% of eCEA and pCEA
      carotid arteries, each, and in the most recent duplex examination in 7% after
      eCEA and 21% after pCEA (P = .003), with no eCEA and two pCEA arteries occluding
      completely during follow-up (P = .29). In 19 carotid arteries with PSV >125 cm/s
      after angle correction (median, 160 cm/s; interquartile range, 146-432 cm/s)
      after eCEA that were subsequently examined by axial imaging, the mean percentage
      stenosis was 8% +/- 11% by NASCET, 11% +/- 5% by ECST, and 20% +/- 9% by CSA
      criteria. For eight pCEA arteries with PSV >125 cm/s (median velocity, 148 cm/s;
      interquartile range, 139-242 cm/s), the corresponding NASCET, ECST, and CSA
      stenoses were 8% +/- 35%, 26% +/- 32%, and 25% +/- 33%, respectively. NASCET
      internal carotid diameter reduction of at least 50% was noted by axial imaging
      after two of the eight pCEAs, and the PSV exceeded 200 cm/s in each case.
      CONCLUSIONS: The presence of hemodynamically significant carotid artery
      restenosis may be overestimated by standard duplex criteria after eCEA and
      perhaps after pCEA. Insufficient information currently exists to determine what
      PSV does correspond to hemodynamically significant restenosis.

PMID- 25758451
TI  - Contemporary management of median arcuate ligament syndrome provides early
      symptom improvement.
AB  - OBJECTIVE: Optimal diagnosis and management of median arcuate ligament (MAL)
      syndrome (MALS) remains unclear in contemporary practice. The advent and
      evolution of laparoscopic and endovascular techniques has redirected management
      toward a less invasive therapeutic algorithm. This study examined our
      contemporary outcomes of patients treated for MALS. METHODS: All patients treated
      for MALS at Dartmouth-Hitchcock Medical Center from 2000 to 2013 were
      retrospectively reviewed. Demographics and comorbidities were recorded. Freedom
      from symptoms and freedom from reintervention were the primary end points. Return
      to work or school was assessed. Follow-up by clinic visits and telephone allowed
      quantitative comparisons among the patients. RESULTS: During the study interval,
      21 patients (24% male), with a median age of 42 years, were treated for MALS. All
      patients complained of abdominal pain in the presence of a celiac stenosis, 16
      (76%) also reported weight loss at the time of presentation, and 57% had a
      concomitant psychiatric history. Diagnostic imaging most commonly used included
      duplex ultrasound (81%), computed tomography angiography (66%), angiography
      (57%), and magnetic resonance angiography (5%). Fourteen patients (67%) underwent
      multiple diagnostic studies. All patients underwent initial laparoscopic MAL
      release. Seven patients (33%) underwent subsequent celiac stent placement in the
      setting of recurrent or unresolved symptoms with persistent celiac stenosis at a
      mean interval of 49 days. Two patients required surgical bypass after an
      endovascular intervention failed. The 6-month freedom from symptoms was 75% and
      freedom from reintervention was 64%. Eighteen patients (81%) reported early
      symptom improvement and weight gain, and 66% were able to return to work.
      CONCLUSIONS: A multidisciplinary treatment approach using initial laparoscopic
      release and subsequent stent placement and bypass surgery provides symptom
      improvement in most patients treated for MALS. The potential placebo effect,
      however, remains uncertain. A significant minority of patients will require
      reintervention, justifying longitudinal surveillance and prudent patient
      selection. Patients can anticipate functional recovery, weight gain, and return
      to work with treatment.

PMID- 25758453
TI  - Characteristics and clinical outcome in patients after popliteal artery injury.
AB  - BACKGROUND: The treatment of popliteal artery injury (PAI) caused by blunt or
      penetrating mechanism is demanding. Concomitant injuries and prolonged ischemia
      are the major causes of lower extremity morbidity and poor rates of limb salvage.
      This study assessed the amputation rate and, subsequently, the therapeutic
      management and clinical outcomes regarding the affect of concomitant injuries
      among patients with PAI in a setting of central European trauma care. METHODS:
      Sixty-four patients (20 female and 44 male), with an average age of 44 years
      (range, 17-79 years) at the time of injury, were evaluated for clinical
      characteristics, concomitant injuries, complications, amputation rates, and
      functional outcome after traumatic PAI. The mechanism of injury was blunt trauma
      in 35 patients (54.7%) and penetrating trauma in 29 (45.3%). The Mangled
      Extremity Severity Score and the Injury Severity Score were assessed initially
      and the modified Functional Independence Measure (FIM) Score at 12 months after
      the primary surgery. RESULTS: Thirty patients (47%) returned to their normal
      activity level within 1 year after trauma, and 16 (25%) were limited in their
      daily activity or suffered from chronic pain symptoms. Within the blunt trauma
      group 26 of 35 patients (74%) sustained severe concomitant injuries, whereas two
      of 29 patients (7%) in the penetrating group showed severe concomitant injuries
      (P < .046). Eleven patients (17%) had to undergo revision surgery due to their
      associated injuries. The median modified FIM score was 10.3, whereas patients
      with blunt trauma had significantly lower FIM score (P < .0082). The median
      Mangled Extremity Severity Score was 6 points (range, 6-16 points). Primary or
      secondary amputation was required in 18 patients (28%) due to failure of
      revascularization. Patients who sustained blunt trauma had significantly higher
      amputation rates than those with penetrating injuries (P < .035). CONCLUSIONS:
      Clinical outcome and limb salvage of patients with PAI were influenced by the
      mechanism of trauma, concomitant injuries, prolonged ischemia time, and the type
      of surgical procedure. Patients after blunt trauma had a higher incidence of
      concomitant injuries, and (comminuted) fractures or knee dislocations and severe
      soft tissue damage had the highest effect on the amputation rate.

PMID- 25758454
TI  - Silencing of eIF3e promotes blood perfusion recovery after limb ischemia through
      stabilization of hypoxia-inducible factor 2alpha activity.
AB  - OBJECTIVE: We previously observed that silencing of eukaryotic translation
      initiation factor 3 subunit e (eIF3e), a hypoxia-independent downregulator of
      hypoxia-inducible factor 2alpha (HIF-2alpha), led to neoangiogenesis by promoting
      HIF-2alpha activity under normoxic conditions. In the current study, we
      investigated whether temporary silencing of eIF3e in muscles affects blood flow
      recovery in a mouse ischemic limb model. METHODS: eIF3e silencing was performed
      using small interfering RNA (siRNA), and changes in gene transcription and
      protein expression were analyzed in vitro using murine primary skeletal muscle
      myoblast and human primary skeletal muscle myoblast cell cultures. In unilateral
      femoral artery ligation experiments, eIF3e siRNA-expressing plasmids were
      injected into the muscles of BALB/c mice near the ligation sites, and tissue
      damage and loss of limb function were scored for 28 days while serial
      measurements of limb perfusions were performed with laser Doppler perfusion
      imaging. RESULTS: Silencing of eIF3e in murine primary skeletal muscle myoblasts
      led to stabilization of HIF-2alpha and upregulation of angiogenic transcripts,
      including basic fibroblast growth factor and platelet-derived growth factor B (P
      < .05), and the supernatant of eIF3e-silenced human primary skeletal muscle
      myoblasts triggered the tube formation of human umbilical vein endothelial cells.
      The in vivo mouse model of hindlimb ischemia revealed that single intramuscular
      injections of eIF3e siRNA-expressing plasmids significantly enhanced perfusion of
      ischemia-damaged limbs (P < .05) at days 7 and 14 and functional recovery at days
      7, 14, and 21 (P < .05). CONCLUSIONS: eIF3e is an angiogenesis suppressor and may
      be a therapeutic target for promoting angiogenesis after ischemic injuries.

PMID- 25758455
TI  - The propargylbenzene dimer: C-H...pi assisted pi-pi stacking.
AB  - The propargylbenzene dimer was investigated using mass selected electronic and
      infrared spectroscopy in combination with quantum chemical calculations. The IR
      spectrum in the acetylenic C-H stretching region indicates that the two
      propargylbenzene units in the dimer are in an almost identical environment. The
      stabilization energies calculated at various levels of theory predict that the
      anti-parallel structure is the most stable isomer. The observed spectra are
      assigned to pi-stacked structures which incorporate C-H...pi interaction. The
      symmetry-adapted perturbation theory (SAPT) based energy decomposition analysis
      reveals that electrostatics contributes around 35% while the rest is due to
      dispersion. Comparison with the phenylacetylene and toluene dimers indicates that
      the higher stabilization energy of the PrBz dimer can be attributed to the
      synergy between the pi-pi stacking and C-H...pi interactions.

PMID- 25758456
TI  - Anne Haffajee: a renaissance woman in periodontal research.

PMID- 25758457
TI  - Supplemental vibrational force during orthodontic alignment: a randomized trial.
AB  - This prospective 3-arm parallel-group randomized clinical trial investigated the
      effect of supplemental vibrational force on rate of orthodontic tooth alignment
      with fixed appliances. Eighty-one subjects (40 males, 41 females; mean age, 14.1
      y) undergoing first premolar extraction-based fixed appliance treatment were
      randomly allocated to treatment supplemented with daily use (20 min) of a
      removable intraoral vibrational device (AcceleDent; OrthoAccel Technologies Inc.;
      n = 29), an identical nonfunctional (sham) device (n = 25), or fixed appliances
      only (n = 27). Mandibular study casts were taken at baseline (treatment start:
      placement of 0.014-in. nickel-titanium arch wire), initial alignment (0.018-in.
      nickel-titanium arch wire), and final alignment (0.019 x 0.025-in. stainless
      steel arch wire). Overall mean irregularity index in the mandibular arch at
      baseline was 8.5 +/- 3.8 mm (95% CI, 7.6 to 9.3) with no significant difference
      between groups (P = 0.73). For the total sample, mean irregularity index at
      initial alignment was 2.7 +/- 2.8 mm (95% CI, 2.2 to 3.4) with no significant
      difference between groups (P = 0.40). Mean time from baseline to initial
      alignment was 59 +/- 25 d (95% CI, 54.5 to 65.6); from initial to final
      alignment, 150 +/- 62.5 d (95% CI, 136 to 165); and baseline to final alignment,
      209 +/- 65 d (95% CI, 195 to 224). Kaplan-Meier analysis demonstrated that
      patterns of alignment were not significantly different among the 3 groups (P =
      0.66). Multivariate linear regression for initial and overall alignment rates
      using initial irregularity index as the covariate showed no significant
      differences among groups. The most important influence on both initial and
      overall rates of alignment was initial irregularity (P = 0.1 * 10(-4)). This
      prospective randomized clinical trial found no evidence that supplemental
      vibrational force can significantly increase the rate of initial tooth movement
      or reduce the amount of time required to achieve final alignment when used in
      conjunction with a preadjusted edgewise fixed appliance (ClinicalTrials.gov
      NCT02314975). 

PMID- 25758459
TI  - Naevus comedonicus syndrome complicated by hidradenitis suppurativa-like lesions
      responding to acitretin treatment.

PMID- 25758458
TI  - Oral Lactobacilli and Dental Caries: A Model for Niche Adaptation in Humans.
AB  - Lactobacilli have been associated with dental caries for over a century. Here, we
      review the pertinent literature along with findings from our own study to
      formulate a working hypothesis about the natural history and role of
      lactobacilli. Unlike most indigenous microbes that stably colonize a host,
      lactobacilli appear to be planktonic, opportunistic settlers that can gather and
      multiply only in certain restrictive niches of the host, at least within the oral
      cavity. We postulate that the following essential requirements are necessary for
      sustained colonization of lactobacilli in humans: 1) a stagnant, retentive niche
      that is mostly anaerobic; 2) a low pH milieu; and 3) ready access to
      carbohydrates. Three sites on the human body meet these specifications: caries
      lesions, the stomach, and the vagina. Only a handful of Lactobacillus species is
      found in caries lesions, but they are largely absent in caries-free children.
      Lactobacilli present in caries lesions represent both a major contributor to
      caries progression and a major reservoir to the gastrointestinal (GI) tract. We
      extend the assertion from other investigators that lactobacilli found in the GI
      tract originate in the oral cavity by proposing that lactobacilli in the oral
      cavity arise from caries lesions. This, in turn, leads us to reflect on the
      health implications of the lactobacilli in the mouth and downstream GI and to
      ponder whether these or any of the Lactobacillus species are truly indigenous to
      the human GI tract or the oral cavity. 

PMID- 25758460
TI  - Current advances in the generation of human iPS cells: implications in cell-based
      regenerative medicine.
AB  - Over the last few years, the generation of induced pluripotent stem cells (iPSCs)
      from human somatic cells has proved to be one of the most potentially useful
      discoveries in regenerative medicine. iPSCs are becoming an invaluable tool to
      study the pathology of different diseases and for drug screening. However,
      several limitations still affect the possibility of applying iPS cell-based
      technology in therapeutic prospects. Most strategies for iPSCs generation are
      based on gene delivery via retroviral or lentiviral vectors, which integrate into
      the host's cell genome, causing a remarkable risk of insertional mutagenesis and
      oncogenic transformation. To avoid such risks, significant advances have been
      made with non-integrative reprogramming strategies. On the other hand, although
      many different kinds of somatic cells have been employed to generate iPSCs, there
      is still no consensus about the ideal type of cell to be reprogrammed. In this
      review we present the recent advances in the generation of human iPSCs,
      discussing their advantages and limitations in terms of safety and efficiency. We
      also present a selection of somatic cell sources, considering their capability to
      be reprogrammed and tissue accessibility. From a translational medicine
      perspective, these two topics will provide evidence to elucidate the most
      suitable combination of reprogramming strategy and cell source to be applied in
      each human iPSC-based therapy. The wide variety of diseases this technology could
      treat opens a hopeful future for regenerative medicine. Copyright (c) 2015 John
      Wiley & Sons, Ltd.

PMID- 25758461
TI  - Retinoic acid signaling regulates development of the dorsal forebrain midline and
      the choroid plexus in the chick.
AB  - The developing forebrain roof plate (RP) contains a transient signaling center,
      perturbations in which have been linked to holoprosencephaly (HPE). Here, we
      describe a novel domain of retinoic acid (RA) signaling that is specific to the
      chick RP and demonstrate that RA signaling is sufficient for inducing
      characteristics of the RP in ectopic locations. We further demonstrate that,
      unlike what has been observed in the mouse, RA signaling is essential for
      invagination of the RP in chick, failure of which leads to an HPE-like phenotype.
      In addition, we found that RA exerts a negative influence on choroid plexus
      differentiation. Thus, our findings identify RA as a novel regulator of chick
      forebrain RP development. 

PMID- 25758463
TI  - Accumulation of the Drosophila Torso-like protein at the blastoderm plasma
      membrane suggests that it translocates from the eggshell.
AB  - The eggshell serves as a depository for proteins that play an important role in
      early embryonic development. In particular, the Drosophila eggshell is
      responsible for transferring asymmetries from the egg chamber to specify the
      regions at both ends of the embryo through the uneven activation of the Torso
      (Tor) receptor in its membrane. This process relies on the restricted expression
      of the gene torso-like (tsl) in subpopulations of follicle cells during oogenesis
      and its protein accumulation at both poles of the eggshell, but it is not known
      how this signal is transmitted to the embryo. Here, we show that Tsl accumulates
      at the embryonic plasma membrane, even in the absence of the Tor receptor.
      However, during oogenesis, we detected Tsl accumulation only at the eggshell.
      These results suggest that there is a two-step mechanism to transfer the
      asymmetric positional cues from the egg chamber into the early embryo: initial
      anchoring of Tsl at the eggshell as it is secreted, followed by its later
      translocation to the egg plasma membrane, where it enables Tor receptor
      activation. Translocation of anchored determinants from the eggshell might then
      regulate the spatial and temporal control of early embryonic developmental
      processes. 

PMID- 25758462
TI  - Dynamic visualization of transcription and RNA subcellular localization in
      zebrafish.
AB  - Live imaging of transcription and RNA dynamics has been successful in cultured
      cells and tissues of vertebrates but is challenging to accomplish in vivo. The
      zebrafish offers important advantages to study these processes--optical
      transparency during embryogenesis, genetic tractability and rapid development.
      Therefore, to study transcription and RNA dynamics in an intact vertebrate
      organism, we have adapted the MS2 RNA-labeling system to zebrafish. By using this
      binary system to coexpress a fluorescent MS2 bacteriophage coat protein (MCP) and
      an RNA of interest tagged with multiple copies of the RNA hairpin MS2-binding
      site (MBS), live-cell imaging of RNA dynamics at single RNA molecule resolution
      has been achieved in other organisms. Here, using a Gateway-compatible MS2
      labeling system, we generated stable transgenic zebrafish lines expressing MCP,
      validated the MBS-MCP interaction and applied the system to investigate zygotic
      genome activation (ZGA) and RNA localization in primordial germ cells (PGCs) in
      zebrafish. Although cleavage stage cells are initially transcriptionally silent,
      we detect transcription of MS2-tagged transcripts driven by the betaactin
      promoter at ~ 3-3.5 h post-fertilization, consistent with the previously reported
      ZGA. Furthermore, we show that MS2-tagged nanos3 3'UTR transcripts localize to
      PGCs, where they are diffusely cytoplasmic and within larger cytoplasmic
      accumulations reminiscent of those displayed by endogenous nanos3. These tools
      provide a new avenue for live-cell imaging of RNA molecules in an intact
      vertebrate. Together with new techniques for targeted genome editing, this system
      will be a valuable tool to tag and study the dynamics of endogenous RNAs during
      zebrafish developmental processes.

PMID- 25758464
TI  - Axonal wrapping in the Drosophila PNS is controlled by glia-derived neuregulin
      homolog Vein.
AB  - Efficient neuronal conductance requires that axons are insulated by glial cells.
      For this, glial membranes need to wrap around axons. Invertebrates show a
      relatively simple extension of glial membranes around the axons, resembling Remak
      fibers formed by Schwann cells in the mammalian peripheral nervous system. To
      unravel the molecular pathways underlying differentiation of glial cells that
      provide axonal wrapping, we are using the genetically amenable Drosophila model.
      At the end of larval life, the wrapping glia differentiates into very large
      cells, spanning more than 1 mm of axonal length. The extension around axonal
      membranes is not influenced by the caliber of the axon or its modality. Using
      cell type-specific gene knockdown we show that the extension of glial membranes
      around the axons is regulated by an autocrine activation of the EGF receptor
      through the neuregulin homolog Vein. This resembles the molecular mechanism
      employed during cell-autonomous reactivation of glial differentiation after
      injury in mammals. We further demonstrate that Vein, produced by the wrapping
      glia, also regulates the formation of septate junctions in the abutting
      subperineurial glia. Moreover, the wrapping glia indirectly controls the
      proliferation of the perineurial glia. Thus, the wrapping glia appears center
      stage to orchestrate the development of the different glial cell layers in a
      peripheral nerve.

PMID- 25758465
TI  - Histone deacetylase inhibitor attenuates neurotoxicity of clioquinol in PC12
      cells.
AB  - Clioquinol is considered to be a causative agent of subacute myelo-optico
      neuropathy (SMON), although the pathogenesis of SMON is yet to be elucidated. We
      have previously shown that clioquinol inhibits nerve growth factor (NGF)-induced
      Trk autophosphorylation in PC12 cells transformed with human Trk cDNA. To explore
      the further mechanism of neuronal damage by clioquinol, we evaluated the
      acetylation status of histones in PC12 cells. Clioquinol reduced the level of
      histone acetylation, and the histone deacetylase (HDAC) inhibitor Trichostatin A
      upregulated acetylated histones and prevented the neuronal cell damage caused by
      clioquinol. In addition, treatment with HDAC inhibitor decreased neurite
      retraction and restored the inhibition of NGF-induced Trk autophosphorylation by
      clioquinol. Thus, clioquinol induced neuronal cell death via deacetylation of
      histones, and HDAC inhibitor alleviates the neurotoxicity of clioquinol.
      Clioquinol is now used as a potential medicine for malignancies and
      neurodegenerative diseases. Therefore, HDAC inhibitors can be used as a candidate
      medicine for the prevention of its side effects on neuronal cells.

PMID- 25758467
TI  - Predictive Factors for Non-Sentinel Lymph Node Metastasis in Patients With
      Clinically Node-Negative Ipsilateral Multiple Breast Cancer Treated With Total
      Mastectomy.
AB  - BACKGROUND: Recent clinical trials have shown that axillary lymph node dissection
      can be omitted even with positive sentinel nodes (SN) unless the patient
      undergoes total mastectomy without irradiation. The aim of our study was to
      identify predictive factors for non-SN metastasis among patients with solitary or
      multiple breast cancer treated with total mastectomy. PATIENTS AND METHODS:
      Clinically node-negative breast cancer patients with pathologically node-positive
      disease treated with total mastectomy and axillary dissection after SN biopsy
      were retrospectively analyzed. Significant pathologic predictive factors for
      positive non-SN metastasis were also examined. RESULTS: There were 47 multiple
      and 143 solitary breast cancer patients. Pathologic diagnosis demonstrated that
      smaller invasion size but larger tumor size, including adjacent noninvasive
      cancer, was observed in multiple breast cancer. The number of involved SNs and
      the rate of non-SN metastasis were similar between the multiple and solitary
      groups. Regarding predictive factors for non-SN metastasis, lymphatic invasion
      and SN macrometastasis were significant factors in the solitary group, and
      pathologic invasion size > 2 cm was the only significant factor in the multiple
      group. CONCLUSION: Larger pathologic invasion size was important for predicting
      non-SN metastasis in multiple breast cancer.

PMID- 25758466
TI  - A novel model of megavoltage radiation-induced oral mucositis in hamsters: Role
      of inflammatory cytokines and nitric oxide.
AB  - PURPOSE: To design a novel model to study Cobalt-60 (Co-60)-induced radiation
      mucositis and to describe the pathways involved in its development. MATERIALS AND
      METHODS: Hamsters' cheeks were treated with Co-60 radiation (10, 20, 30 or 35
      Gy). Three days later, oral mucosa scarification was performed with a needle. The
      animals were euthanized at day 13 (D + 13) after irradiation. Gross and
      microscopic alterations were evaluated by a new score system that we developed.
      Also, neutrophil infiltration, tumor necrosis factor-alpha (TNF-alpha),
      interleukin (IL)-1beta, IL-10, inducible nitric oxide synthase (iNOS), nitric
      oxide (NO) and nitrite were assessed in oral mucosa. We also tried to establish
      the roles of TNF-alpha and IL-1beta and iNOS in our model using pharmacological
      approaches with pentoxiphylline (PTX) and aminoguanidine (AMG), respectively.
      RESULTS: We found that a single administration of 35 Gy of Co-60, followed by
      mechanical scratches 3 days later, induced oral mucositis in hamsters. Animals
      with mucositis lost weight and had a survival median of 13 days, the time at
      which peak inflammation occurs. We noticed increased levels of NO, iNOS, TNF
      alpha and IL-1beta and a reduced concentration of IL-10. PTX partially prevented
      the mucositis phenotype by reducing the levels of inflammatory mediators and iNOS
      expression. Additionally, AMG, a selective inhibitor of iNOS, reduced Co-60
      induced oral mucositis through reducing NO production. CONCLUSION: We described a
      novel model of megavoltage radiation-induced oral mucositis in hamsters. TNF
      alpha, IL-1beta and NO seem to play a role in the pathophysiology of this model.

PMID- 25758469
TI  - Berry phases and the intrinsic thermal Hall effect in high-temperature cuprate
      superconductors.
AB  - Bogolyubov quasiparticles move in a practically uniform magnetic field in the
      vortex state of high-temperature cuprate superconductors. When set in motion by
      an externally applied heat current, the quasiparticles' trajectories may bend,
      causing a temperature gradient perpendicular to the heat current and the applied
      magnetic field, resulting in the thermal Hall effect. Here we relate this effect
      to the Berry curvature of quasiparticle magnetic sub-bands, and calculate the
      dependence of the intrinsic thermal Hall conductivity on superconductor's
      temperature, magnetic field and the amplitude of the d-wave pairing. The
      intrinsic contribution to thermal Hall conductivity displays a rapid onset with
      increasing temperature, which compares favourably with existing experiments at
      high magnetic field on the highest purity samples. Because such temperature onset
      is related to the pairing amplitude, our finding may help to settle a much
      debated question of the bulk value of the pairing strength in cuprate
      superconductors in magnetic field. 

PMID- 25758468
TI  - Real-time cytometric assay of nitric oxide and superoxide interaction in
      peripheral blood monocytes: A no-wash, no-lyse kinetic method.
AB  - BACKGROUND: Nitric oxide (NO) and its related reactive nitrogen species (RNS) and
      reactive oxygen species (ROS) are crucial in monocyte responses against pathogens
      and also in inflammatory conditions. Central to both processes is the generation
      of the strong oxidant peroxynitrite (ONOO) by a fast reaction between NO and
      superoxide anion. ONOO is a biochemical junction for ROS- and RNS cytotoxicity
      and causes protein nitrosylation. Circulating by-products of protein
      nitrosylation are early biomarkers of inflammation-based conditions, including
      minimal hepatic encephalopathy in cirrhotic patients (Montoliu et al., Am J
      Gastroenterol 2011; 106:1629-1637). In this context, we have designed a novel no
      wash, no-lyse real-time flow cytometry assay to detect and follow-up the NO- and
      superoxide-driven generation of ONOO in peripheral blood monocytes. METHODS:
      Whole blood samples were stained with CD45 and CD14 antibodies plus one of a
      series of fluorescent probes sensitive to RNS, ROS, or glutathione, namely 4
      amino-5-methylamino-2',7'-difluorofluorescein diacetate, dihydrorhodamine 123,
      MitoSOX Red, dihydroethidium, and 5-chloromethylfluorescein diacetate. Samples
      were exposed sequentially to a NO donor and three different superoxide donors,
      and analyzed in real time by kinetic flow cytometry. Relevant kinetic
      descriptors, such as the rate of fluorescence change, were calculated from the
      kinetic plot. RESULTS: The generation of ONOO, which consumes both NO and
      superoxide, led to a decrease in the intensity of the cellular fluorescence of
      the probes sensitive to these molecules. CONCLUSION: This is a fast and simple
      assay that may be used to monitor the intracellular generation of ONOO in
      physiological, pathological, and pharmacological contexts. (c) 2015 International
      Clinical Cytometry Society.

PMID- 25758471
TI  - L-DOPA-induced dyskinesia, is striatal dopamine depletion a requisite?
AB  - l-3,4-Dihydroxyphenylalanine (L-DOPA) is currently the most effective drug
      available to treat the symptoms of Parkinson's disease (PD). A limitation is that
      chronic administration of L-DOPA almost invariably, but not universally, leads to
      the development of abnormal involuntary movements, dyskinesia. Research suggests
      that striatal dopamine depletion is an important aetiological factor leading to
      dyskinesia development. However, in studies where L-DOPA was administered to
      normal animals and human subjects not afflicted by PD, abnormal involuntary
      movements were sometimes elicited. These studies are reviewed here and their
      potential significance for the pathophysiology of dyskinesia is discussed. It is
      concluded that, if striatal dopamine depletion may not be a requisite for the
      development of dyskinesia, it probably acts as a permissive factor, at least with
      the doses commonly employed in the clinic. 

PMID- 25758470
TI  - Short- and long-term benefits of drug-eluting stents compared to bare metal
      stents even in treatment for large coronary arteries.
AB  - Although drug-eluting stents (DES) for percutaneous coronary intervention (PCI)
      have dramatically reduced the incidence of in-stent restenosis, their deployment
      for large-size coronary lesions is still controversial because of problems such
      as late in-stent thrombosis and late catch-up in DES. We aimed to evaluate the
      long-term outcome beyond 2 years of bare metal stents (BMS) as compared with DES
      in large vessels. Consecutive 228 patients who underwent PCI with large-size
      stents (>3.5 mm in diameter) in our hospital were enrolled in this study. The end
      points of this study are target lesion revascularization (TLR) and occurrence of
      major adverse cardiac events (MACE) for subject patients. We analyzed 183
      patients (152 men, mean age 65.8 +/- 10.5 years) whose outcome could be followed
      up for at least 2 years. At the first 8-month follow-up, clinically driven TLR
      rate was significantly higher in patients who received BMS than those who
      received DES (17.2 vs. 2.2 %, p < 0.05), although the rate of TLR was not
      different between the 2 groups beyond 8 months. Thus, overall rate of TLR was
      higher in BMS than in DES (22.7 vs. 5.4 %, p < 0.05). Under these conditions, the
      higher rate of TLR for BMS was observed in simple as well as complex lesions with
      or without diabetes, although there were no significant differences in MACE
      between BMS and DES. Multivariate analysis showed that BMS was an only
      independent factor of TLR at the 8 month follow-up period [p = 0.004, odds ratio
      9.58, 95 % confidence interval (2.10-43.8)]. These results demonstrate that the
      rate of in-stent restenosis in large-size coronary lesions was transiently higher
      in the first 8 months for patients implanted with BMS compared with DES in which
      no in-stent thrombosis and TLR beyond 2 years were observed. We suggest using the
      DES even in large-size coronary lesions in terms of short- and long-term
      outcomes. 

PMID- 25758472
TI  - ATON: results from a Phase II randomized trial of the B-cell-targeting agent
      atacicept in patients with optic neuritis.
AB  - The 36-week ATON study compared the efficacy and safety of atacicept with
      matching placebo in 34 patients with unilateral optic neuritis as a clinically
      isolated syndrome. Atacicept (150mg) was administered twice weekly for 4weeks
      (loading period), then once weekly for 32weeks. The ATON study was terminated
      prematurely by the sponsor when an independent Data and Safety Monitoring Board
      review observed increased multiple sclerosis (MS)-related disease activity in the
      atacicept arms of the concurrent ATAcicept in MS (ATAMS) study. Analysis of the
      prematurely terminated ATON study showed that the mean (standard deviation)
      change from baseline in retinal nerve fiber layer thickness at last observed
      value in the affected eye was -8.6 (10.1) MUm in patients treated with atacicept
      (n=15) compared with -17.3 (15.2) MUm in patients treated with placebo (n=16). In
      the atacicept treatment group, a higher proportion of patients converted to
      clinically definite MS during the double-blind period compared with placebo
      (35.3% [6/17] vs 17.6% [3/17]). Treatment-emergent adverse events were similar
      across both treatment groups in the double-blind period. A dichotomy emerged with
      more atacicept-treated patients converting to relapsing-remitting MS compared
      with placebo-treated patients, despite the same patients experiencing less axonal
      loss after an optic neuritis event. 

PMID- 25758473
TI  - Vulnerable patients deserve regulated care.
AB  - Ask nurses of a certain age about changes to the profession over the past 30
      years or so and many will refer with dismay to the demise of enrolled nurses
      (ENs). For younger readers or those whose memories have faded, ENs completed a
      two-year, apprentice-style training programme before going on to deliver highly
      practical hands-on care. 

PMID- 25758475
TI  - Healthcare support workers given strategy for career development.
AB  - A national framework setting out how employers should develop a skilled and
      knowledgeable healthcare support workforce has been launched by Health Education
      England. 

PMID- 25758476
TI  - Maternity care review's aims are set out in wake of furness report.

PMID- 25758477
TI  - Pay deal acceptance signals end of long dispute.

PMID- 25758478
TI  - NMC urges staff to engage early with the FtP process.

PMID- 25758479
TI  - Minimum staffing ratios failed to gain Welsh Government support.

PMID- 25758480
TI  - Ebola nurse free to return to work.

PMID- 25758481
TI  - Simple measures improve inpatient sleep quality.

PMID- 25758482
TI  - New role at QNI for district nurse.

PMID- 25758485
TI  - Study finds ideal ward has a mix of single rooms and multi-bed bays.

PMID- 25758486
TI  - 'Large chunk of expertise' missing from cancer services task force.
AB  - A task force set up by NHS England to shape the future of cancer services in
      England includes doctors, charity representatives, a patient and a council chief
      executive - but no nurses, despite there being more than 3,000 specialist adult
      cancer nurses in England. 

PMID- 25758492
TI  - Urinary incontinence.

PMID- 25758493
TI  - Simple truths about dementia.

PMID- 25758494
TI  - A coping strategy.

PMID- 25758495
TI  - Urgent response to cancer.
AB  - Nurses increasingly encounter patients with cancer who experience potentially
      fatal side effects of cancer treatments. In her new role with Macmillan Cancer
      Support, Philippa Jones is developing acute oncology services across the UK that
      will support patients needing urgent care and help avoid hospital admissions.

PMID- 25758502
TI  - Medicines management.
AB  - Medication errors are the second most reported incident type in the NHS. Other
      concerns around medicines management include poor medicines security, theft and
      poor administration practice. 

PMID- 25758503
TI  - Starting out - Helping to manage a patient's care underlined the skills I had
      learned.

PMID- 25758509
TI  - Being open about my gender dysphoria led to serious abuse.

PMID- 25758510
TI  - We urge early engagement with the fitness to practise process.

PMID- 25758511
TI  - No clean bill of health for nurses who wash their uniforms at home.

PMID- 25758513
TI  - Safe staffing could make a big difference to care and morale.

PMID- 25758515
TI  - Our derisory pay offer in no way makes up for years of restraint.

PMID- 25758517
TI  - Improving sleep for patients in acute hospitals.
AB  - Sleep is important to health and recovery from illness, but is known to be
      difficult in hospital. This article describes a quality improvement project
      conducted on 18 wards in acute hospitals. Patients reported sleeping an average
      of five hours per night, and 47% (352/749) rated their sleep quality as good or
      excellent in hospital. Individualised ward action plans were implemented. At
      follow up, disturbance by noise and light had fallen significantly and 69%
      (540/783) of patients rated their sleep as good or excellent, 22% more than
      before the intervention (P<0.001). Local interventions such as improving staff
      awareness of noise, installing window blinds and turning down equipment alarms
      improved the patient experience of sleep. 

PMID- 25758518
TI  - Planning a research project.
AB  - The planning stage of any research project is one of the most important stages in
      the research process. This article offers insight into the important issues a
      researcher needs to consider when planning his or her research, including how to
      develop a research protocol, obtaining research funding, seeking academic, peer
      and social support, gaining research ethics and governance approval and planning
      a research schedule. Careful planning ensures that the research project is
      achievable and can be completed on time, with the funding available. 

PMID- 25758519
TI  - Managing malnutrition in patients with dementia.
AB  - As dementia progresses, an individual may experience increasing difficulties in
      eating and drinking safely. Evidence suggests that admission to hospital may
      exacerbate these problems. This article aims to familiarise readers with some of
      the issues associated with providing good nutritional care for a patient with
      dementia in hospital. Strategies to address the maintenance of oral intake are
      suggested. The article also explores the use of artificial nutrition in dementia,
      with examples to clarify when its use may be helpful. 

PMID- 25758520
TI  - End of life care.
AB  - End of life care is challenging, rewarding and a privileged experience,
      irrespective of where death occurs - in a hospital, care home, hospice, prison or
      at home. The CPD article was a reminder that death is a deeply personal and
      social experience, and one where individuals must be afforded dignity and
      respect. People who are dying should be referred to as individuals or persons,
      and not as patients. 

PMID- 25758521
TI  - Quality and equality.

PMID- 25758523
TI  - Alternative path to practice.

PMID- 25758525
TI  - Student life - Inspirational experience.

PMID- 25758526
TI  - Differential risks in men and women for first and recurrent venous thrombosis:
      the role of genes and environment: reply.

PMID- 25758527
TI  - Pityriasis rubra pilaris-like eruption with dermatomyositis and diffuse cutaneous
      systemic sclerosis overlap.

PMID- 25758529
TI  - Exploring the Relationship Between Mild Traumatic Brain Injury Exposure and the
      Presence and Severity of Postconcussive Symptoms Among Veterans Deployed to Iraq
      and Afghanistan.
AB  - OBJECTIVE: The aim of this study was to describe the association between mild
      traumatic brain injury (mTBI) and persisting postconcussive symptoms according to
      symptom category, number, and severity. DESIGN: The study design was
      observational. PARTICIPANTS: The study sample comprised veterans (>=18 years of
      age) deployed in Operation Enduring Freedom and Operation Iraqi Freedom (OEF/OIF)
      conflicts who had not received any treatment for mTBI in the 30 days preceding
      study enrollment. METHODS: Veterans were interviewed and completed testing in a
      single day. The Standard TBI Diagnostic Interview and the Clinician-Administered
      PTSD Scale were used. Testing included the Neurobehavioral Symptom Inventory and
      a full neuropsychological battery. Gold standard classification methods were
      utilized to determine presence/absence of mTBI. For each of the 5 symptom
      outcomes, an adjusted multiple linear regression model (negative binomial count
      models) accounting for effects of socio-demographic variables and behavioral
      health conditions was used. MAIN OUTCOME MEASURES: Self-report of neurobehavioral
      symptoms categorized as affective, cognitive, somatic, and vestibular symptoms,
      in addition to the instruments specified above. RESULTS: OEF/OIF veterans with
      mTBI, relative to veterans with no mTBI, were observed to have 30% more symptoms
      overall (P < .001), 34% more somatic symptoms (P < .001), 22% more cognitive
      symptoms (P = .008), 15% more affective symptoms (P = .017), and 59% more
      vestibular symptoms (P < .001). For adjusted models, variables significantly
      related to number of symptoms across all 4 symptom categories were anxiety (all P
      < .001) and insomnia (all P < .001). For the adjusted models, variables
      significantly related to symptom severity across all 4 symptom categories were
      insomnia (all P < .001), depression (P < .001-.05) and anxiety (all, P < .001).
      CONCLUSIONS: OEF/OIF veterans with mTBI, relative to veterans with no mTBI, have
      significantly more and significantly more severe persisting symptoms, with
      vestibular symptoms reported with the greatest frequency. After accounting for
      behavioral health conditions and socio-demographic factors, OEF/OIF veterans with
      mTBI compared to veterans without mTBI had significantly more cognitive,
      affective, vestibular, and somatic symptoms persisting 4.8 years after the mTBI
      event(s).

PMID- 25758530
TI  - A Survey of Runners' Attitudes Toward and Experiences With Minimally Shod
      Running.
AB  - OBJECTIVE: To investigate the characteristics, perceptions, motivating factors,
      experiences, and injury rates of runners who practice minimally shod running.
      DESIGN: Survey. SETTING: web-based questionnaire. PARTICIPANTS: Five-hundred
      sixty-six members of the Chicago Area Runner's Association. METHODS: A link to a
      31-question online survey was e-mailed to members of Chicago Area Runner's
      Association. Questions covered demographic information, use of minimalist-style
      running shoes (MSRS), injury rates, and change in pain. MAIN OUTCOME MEASURES:
      Use of MSRS, occurrence or improvement of injury/pain, regions of injury/pain,
      reasons for or for not using MSRS. RESULTS: One-hundred seventy-five (31%)
      respondents had practiced minimally shod running, and the most common motivating
      factor was to decrease injuries and/or pain. Fifty-one respondents (29%) suffered
      an injury or pain while wearing MSRS, with the most common body part involved
      being the foot. Fifty-four respondents (31%) had an injury that improved after
      adopting minimally shod running; the most common area involved was the knee. One
      hundred twenty respondents (69%) were still using MSRS. Of those who stopped
      using MSRS, the main reason was development of an injury or pain. The most common
      reason that respondents have not tried minimally shod running is a fear of
      developing an injury. CONCLUSION: This survey-based study demonstrated that the
      use of MSRS is common, largely as the result of a perception that they may reduce
      injuries or pain. Reductions and occurrences of injury/pain with minimally shod
      running were reported in approximately equal numbers. The most common site of
      reported injury/pain reduction was the knee, whereas the most common reported
      site of injury/pain occurrence was the foot. Fear of developing pain or injury is
      the most common reason runners are reluctant to try minimally shod running.

PMID- 25758528
TI  - RB loss in resistant EGFR mutant lung adenocarcinomas that transform to small
      cell lung cancer.
AB  - Tyrosine kinase inhibitors are effective treatments for non-small-cell lung
      cancers (NSCLCs) with epidermal growth factor receptor (EGFR) mutations. However,
      relapse typically occurs after an average of 1 year of continuous treatment. A
      fundamental histological transformation from NSCLC to small-cell lung cancer
      (SCLC) is observed in a subset of the resistant cancers, but the molecular
      changes associated with this transformation remain unknown. Analysis of tumour
      samples and cell lines derived from resistant EGFR mutant patients revealed that
      Retinoblastoma (RB) is lost in 100% of these SCLC transformed cases, but rarely
      in those that remain NSCLC. Further, increased neuroendocrine marker and
      decreased EGFR expression as well as greater sensitivity to BCL2 family
      inhibition are observed in resistant SCLC transformed cancers compared with
      resistant NSCLCs. Together, these findings suggest that this subset of resistant
      cancers ultimately adopt many of the molecular and phenotypic characteristics of
      classical SCLC. 

PMID- 25758532
TI  - Influence of Knee Pain and Low Back Pain on the Quality of Life in Adults Older
      Than 50 Years of Age.
AB  - OBJECTIVES: To investigate the impact of knee pain and low back pain (LBP) on
      quality of life (QoL) in people >=50 years of age. DESIGN: Cross-sectional study.
      SETTING: A nationwide survey. PARTICIPANTS: A total of 1295 men and 1658 women
      aged >=50 years from the Fifth Korea National Health and Nutrition Examination
      Survey, conducted in 2010. METHODS: Knee pain and LBP were assessed by a
      questionnaire, and QoL was assessed by the EuroQol (EQ)-5D, consisting of the EQ
      5D descriptive system and the EuroQol visual analogue scale (EQ-VAS). Multiple
      linear regression models were used to evaluate associations between knee pain or
      LBP and the EQ-5D index or EQ-VAS score. MAIN OUTCOME MEASUREMENTS: Standardized
      coefficient (beta) for QoL according to the presence of knee pain or LBP.
      RESULTS: Both men and women with knee pain or LBP had a lower QoL than those
      without them in all dimensions of the EQ-5D, EQ-5D index, and EQ-VAS scores.
      Compared with most other chronic diseases, knee pain and LBP showed stronger
      negative correlations with the EQ-5D index and EQ-VAS score. In men, LBP showed a
      stronger negative correlation with the EQ-VAS score than knee pain. The relative
      impact of LBP on knee pain was greater in people aged >=65 years than in people
      aged 50-64 years, especially men. CONCLUSIONS: These results suggest that knee
      pain and LBP are important factors affecting QoL in middle-aged and elderly
      people and that LBP may be relatively more important than knee pain in elderly
      people, especially men. Proper management and prevention of these conditions can
      help to improve QoL.

PMID- 25758531
TI  - Medial and Lateral Heel Whips: Prevalence and Characteristics in Recreational
      Runners.
AB  - OBJECTIVE: To investigate the prevalence and characteristics of recreational
      runners with medial and lateral heel whips. DESIGN: Observational cohort study.
      SETTING: Clinical research laboratory. PARTICIPANTS: A total of 256
      recreationally active runners and joggers participated. MAIN OUTCOME MEASURES:
      High-definition video was acquired from a posterior view while runners ran at a
      self-selected pace on a treadmill. Heel whips, defined as the medial or lateral
      rotation of the foot in the transverse plane during initial swing, were measured
      with Dartfish software. Subjects were stratified by direction (medial and
      lateral) and severity (W_5-10 = 5-10 degrees; W_10+ = >10 degrees) of heel whip.
      Body mass index and gender comparisons, as well as measurement reliability, also
      were explored. RESULTS: Mean heel whip angle across runners was 0.4 degrees
      (medial) with a standard deviation of 9.2 degrees. Of the 512 feet analyzed, 274
      (54%) demonstrated a 5 degree whip or greater. There was a similar number of
      medial and lateral heel whips observed (27% each). Female runners were twice as
      likely to demonstrate a lateral heel whip of greater than 8.9 degrees. Overweight
      runners had more medially directed whips when compared with normal and
      underweight runners. CONCLUSIONS: More than half of the recreational runners
      studied were observed to have a medial or lateral heel whip of greater than 5
      degrees. These data reveal the age, body mass index, and gender distribution of
      recreational runners with and without heel whips.

PMID- 25758534
TI  - Endocrine-disrupting compounds in reclaimed water and residential ponds and
      exposure potential for dislodgeable residues in turf irrigated with reclaimed
      water.
AB  - Endocrine-disrupting chemicals (EDCs) occur in reclaimed water (RW), which may
      serve as an exposure source for humans. The presence of EDCs in RW used to
      irrigate turf and in nearby water-retention ponds was determined. In addition,
      the total dislodgeable mass of each EDC was determined after irrigation (using
      RW) to simulate exposure of a 3-year-child playing in turf grass recently
      irrigated with RW. Five EDCs (estrone, 17beta-estradiol, 17alpha
      ethynylestradiol, bisphenol A, and 4-n-nonylphenol) were quantified in 28 samples
      of RWs (wastewater-treatment plant effluents) and 88 samples from residential
      surface water-retention ponds. St. Augustine variety of turf grass was irrigated
      with spiked RW to study dislodgement of the five EDCs overtime using a drag-sled
      method. Grass clippings were analyzed to relate masses of EDC on grass with
      masses dislodged. EDCs were detected in both RW and ponds at ng/L concentrations.
      Maximum EDC masses were dislodged immediately after irrigation. Dislodged masses
      of estrone and 17beta-estradiol are two separate EDCs, 17beta-estradiol and
      17alpha-ethynylestradiol decreased rapidly and were lower than detection limits 4
      h after application. Dislodged bisphenol-A and nonylphenol decreased more slowly
      but were not detected 6 h after application. Avoiding contact with recently
      irrigated turf grass should decrease the risks of exposure to these EDCs. 

PMID- 25758535
TI  - Nickel-induced morphology change of mesostructured alumina with enhanced
      catalytic activity for selective CO methanation.
AB  - Nickel-induced morphology change of mesostructured alumina with amorphous walls
      to bayerite tetrahedra when treated in water, and then to gamma-alumina with worm
      like mesopores topologically after it was calcined at 400  degrees C is reported.
      The catalytic activity for selective CO methanation increased significantly after
      this treatment. 

PMID- 25758533
TI  - Quercetin attenuates lactate production and extracellular matrix secretion in
      keratoconus.
AB  - Keratoconus(KC) is an ecstatic corneal disease leading to corneal-thinning and
      the formation of a cone-like cornea. Elevated lactate levels, increased oxidative
      stress, and myofibroblast formation have all been previously reported. In the
      current study, we assess the role of Quercetin on collagen secretion and
      myofibroblast formation in KC in vitro. Human corneal fibroblasts(HCFs) and human
      keratoconus cells(HKCs) were treated with a stable Vitamin C derivative and
      cultured for 4 weeks, stimulating formation of a self-assembled extracellular
      matrix. All samples were analyzed using Western blots and targeted tandem mass
      spectrometry. Our data showed that Quercetin significantly down regulates
      myofibroblast differentiation and fibrotic markers, such as alpha-smooth muscle
      actin (alpha-SMA) and Collagen III (Col III), in both HCFs and HKCs. Collagen III
      secretion was reduced 80% in both HCFs and HKCs following Quercetin treatment.
      Furthermore, Quercetin reduced lactate production by HKCs to normal HCF levels.
      Quercetin down regulated TGF-betaR2 and TGF-beta2 expression in HKCs suggesting a
      significant link to the TGF-beta pathway. These results assert that Quercetin is
      a key regulator of fibrotic markers and ECM assembly by modulating cellular
      metabolism and TGF-beta signaling. Our study suggests that Quercetin is a
      potential therapeutic for treatment of corneal dystrophies, such as KC. 

PMID- 25758536
TI  - Effect of genetic polymorphisms involved in folate metabolism on the
      concentration of serum folate and plasma total homocysteine (p-tHcy) in healthy
      subjects after short-term folic acid supplementation: a randomized, double blind,
      crossover study.
AB  - Data on the effect of combined genetic polymorphisms, involved in folate
      metabolism, on the concentration of serum folate after folic acid supplementation
      are scarce. Therefore, we investigated the impact of seven gene polymorphisms on
      the concentration of serum folate and p-tHcy in healthy subjects after short-term
      folic acid supplementation. In a randomized, double blind, crossover study,
      apparently healthy subjects were given either 0.8 mg folic acid per day (n = 46)
      or placebo (n = 45) for 14 days. The washout period was 14 days. Fasting blood
      samples were collected on day 1, 15, 30 and 45. Data on subjects on folic acid
      supplementation (n = 91) and on placebo (n = 45) were used for the statistical
      analysis. The concentration of serum folate increased higher in subjects with
      higher age (53.5 +/- 7.0 years) than in subjects with lower age (24.3 +/- 3.2
      years) after folic acid supplementation (p = 0.006). The baseline concentration
      of serum folate in subjects with polymorphism combination, reduced folate carrier
      protein, RFC1-80 GA and methylenetetrahydrofolate reductase, MTHFR677 CT+TT, was
      lower than RFC1-80 AA and MTHFR677 CT+TT (p = 0.002). After folic acid
      supplementation, a higher increase in the concentration of serum folate was
      detected in subjects with polymorphism combination RFC1-80 GA and MTHFR677 CC
      than RFC1-80 GG and MTHFR CT+TT combination (p < 0.0001). The baseline
      concentration of plasma total homocysteine (p-tHcy) was altered by combined
      polymorphisms in genes associated with folate metabolism. After folic acid
      supplementation, in subjects with combined polymorphisms in
      methylenetetrahydrofolate dehydrogenase, MTHFD1-1958 and MTHFR-677 genes, the
      concentration of p-tHcy was changed (p = 0.002). The combination of RFC1-80 and
      MTHFR-677 polymorphisms had a profound affect on the concentration of serum
      folate in healthy subjects before and after folic acid supplementation. 

PMID- 25758537
TI  - High level of fecal calprotectin at age 2 months as a marker of intestinal
      inflammation predicts atopic dermatitis and asthma by age 6.
AB  - BACKGROUND: Gut microbiota and intestinal inflammation regulate the development
      of immune-mediated diseases, such as allergies. Fecal calprotectin is a biomarker
      of intestinal inflammation. OBJECTIVE: We evaluated the association of early-age
      fecal calprotectin levels to the later development of allergic diseases in
      children from farming and non-farming environments and further studied the effect
      of gut microbiota on the fecal calprotectin levels. METHODS: Fecal calprotectin
      was measured from 758 infants participating in the PASTURE study at the age of 2
      months using the ELISA method. Serum-specific IgE levels were measured at 6 years
      of age. Data of environmental factors, doctor-diagnosed atopic dermatitis (AD)
      and asthma were collected by questionnaire. Multivariate logistic regression
      models were used for analysis. The composition of fecal microbiota was analysed
      in a subgroup of 120 infants with 16S rRNA pyrosequencing. The effect of
      Escherichia coli lipopolysaccharide (LPS) on in vitro monocyte IL-10 secretion
      was studied by flow cytometry. RESULTS: The infants with high fecal calprotectin
      levels at 2 months, that is above the 90th percentile, had an increased risk of
      developing AD and asthma/asthmatic bronchitis by the age of 6 years (aOR 2.02
      (1.06-3.85) and 2.41 (1.25-4.64), respectively). High fecal calprotectin levels
      correlated negatively with fecal Escherichia. LPS from E. coli stimulated
      production of IL-10 in monocytes. CONCLUSION AND CLINICAL RELEVANCE: High degree
      intestinal inflammation at 2 months of age, detected as high fecal calprotectin,
      predicted asthma and AD by the age of 6 years and was linked to low abundance of
      fecal Escherichia. Impaired IL-10 activation due to the lack of colonization with
      E. coli could explain the intestinal inflammation associated high fecal
      calprotectin and later risk of asthma and AD. Our results have implications for
      the design of probiotic treatments and suggest that early intestinal colonization
      has long-term health effects.

PMID- 25758538
TI  - Highly efficient water-mediated approach to access benzazoles: metal catalyst and
      base-free synthesis of 2-substituted benzimidazoles, benzoxazoles, and
      benzothiazoles.
AB  - An efficient water-catalyzed method has been developed for the synthesis of 2
      substituted benzimidazoles, benzoxazoles, and benzothiazoles in one step. The
      present method excludes the usage of toxic metal catalysts and bases to produce
      benzazoles in good to excellent yields. An efficient and versatile water-mediated
      method has been established for the synthesis of various 2-arylbenzazoles. The
      present protocol excludes the usage of any catalyst and additive provided
      excellent selectivities and yields with high functional group tolerance for the
      synthesis of 2-arylated benzimidazoles, benzoxazoles, and benzothiazoles.
      Benzazolones were also synthesized using similar reaction protocol. 

PMID- 25758539
TI  - A one-pot three-component reaction involving 2-aminochromone in aqueous micellar
      medium: a green synthesis of hexahydrochromeno[2,3-b]quinolinedione.
AB  - An efficient and green synthesis of hitherto unreported 11-(chromen-3-yl)-8,8
      dimethyl-8,9-dihydro-6H-chromeno[2,3-b]quinoline-10,12(7H,11H)-dione has been
      accomplished by a three-component reaction involving 2-aminochromone, chromone-3
      carbaldehyde, and 5,5-dimethyl-1,3-cyclohexanedione (dimedone) in 0.5 M aqueous
      SDS solution. The mechanism of the reaction has been studied by isolating the
      reaction intermediate. This methodology features eco-friendly reaction
      conditions, a simple working procedure, high atom-economy and high efficiency in
      product formation.

PMID- 25758540
TI  - A facile tandem Michael addition/O-cyclization/elimination route to novel
      chromeno[3,2-c]pyridines.
AB  - A facile and efficient synthesis of a library of novel chromeno[3,2-c]pyridines
      has been achieved from the reaction of various 3,5-((E)-arylidene)-1
      alkylpiperidin-4-ones and cyclic 1,3-diketones. The reaction presumably occurred
      via tandem Michael addition-intramolecular O-cyclization-elimination sequence in
      a single operation.

PMID- 25758541
TI  - Evaluation of ameliorative effect of curcumin on imidacloprid-induced male
      reproductive toxicity in wistar rats.
AB  - This study was undertaken to investigate the toxic effects of imidacloprid (IM)
      on male reproductive system and ameliorative effect of curcumin (CMN) in male
      Wistar rats. For this purpose, IM (45 and 90 mg/kg, body weight) and CMN (100
      mg/kg, body weight) were administered orally to the rats either alone or in
      combinations for a period of 28 days. At the end of experiment, male reproductive
      toxicity parameters (total sperm count and sperm abnormalities), testosterone
      level, steroidal enzymatic activity [3beta-hydroxysteroid dehydrogenase (3beta
      HSD) and 17beta-HSD], and oxidative stress indicators were estimated in testis
      and plasma. IM treatments resulted in significant decrease (p < 0.05) in total
      epididymal sperm count, sperm motility, live sperm count, and increase (p < 0.05)
      in sperm abnormalities. Activities of gamma-glutamyl transpeptidase, lactate
      dehydrogenase-x, and sorbitol dehydrogenase were significantly increased (p <
      0.05), while, 3beta-HSD and 17beta-HSD enzymatic activity along with testosterone
      concentration in testis and plasma were decreased significantly (p < 0.05) in IM
      treated rats. IM exposure resulted in significant increase (p < 0.05) in LPO and
      decrease (p < 0.05) in GSH level along with decreased activities of CAT, SOD,
      GPx, and GST. IM-treated rats showed histopathological alterations in testis and
      epididymis. However, the reproductive toxicity parameters, oxidative stress
      indicators, and histopathological changes were minimized and functional
      restorations were noticed by co-administration of CMN in IM-treated rats. The
      results of this study suggest that IM-induced male reproductive toxic effects
      could be ameliorated by CMN supplementation. (c) 2015 Wiley Periodicals, Inc.
      Environ Toxicol 31: 1250-1263, 2016. 

PMID- 25758542
TI  - Stimulation of the Angiotensin II AT2 Receptor is Anti-inflammatory in Human
      Lipopolysaccharide-Activated Monocytic Cells.
AB  - Recently, AT2 receptors have been discovered on the surface of human
      immunocompetent cells such as monocytes. Data on regulative properties of this
      receptor on the cellular immune response are poor. We hypothesized that direct
      stimulation of the AT2 receptor mediates anti-inflammatory responses in these
      cells. Human monocytic THP-1 and U937 cells were stimulated with
      lipopolysaccharide (LPS) and the selective AT2 receptor agonist Compound 21
      (C21). Expression of pro- and anti-inflammatory cytokines IL-6, IL-10, tumor
      necrosis factor-alpha (TNFalpha), and IL-1beta were analyzed on both the
      transcriptional and the translational level over course of time. Treatment with
      C21 attenuated the expression of TNFalpha, IL-6, and IL-10 after LPS challenge in
      both cell lines in a time- and dose-dependent manner. We conclude that selective
      AT2 receptor stimulation acts anti-inflammatory in human monocytes. Modulation of
      cytokine response by AT2 receptor activation might be a beneficial and novel
      treatment concept in inflammatory conditions. 

PMID- 25758543
TI  - Gradient nonlinearity correction to improve apparent diffusion coefficient
      accuracy and standardization in the american college of radiology imaging network
      6698 breast cancer trial.
AB  - PURPOSE: To evaluate a gradient nonlinearity correction (GNC) program for
      quantitative apparent diffusion coefficient (ADC) measurements on phantom and
      human subject diffusion-weighted (DW) magnetic resonance imaging (MRI) scans in a
      multicenter breast cancer treatment response study MATERIALS AND METHODS: A GNC
      program using fifth-order spherical harmonics for gradient modeling was applied
      retrospectively to qualification phantom and human subject scans. Ice-water
      phantoms of known diffusion coefficient were scanned at five different study
      centers with different scanners and receiver coils. Human in vivo data consisted
      of baseline and early-treatment exams on 54 patients from four sites. ADC maps
      were generated with and without GNC. Regions of interest were defined to quantify
      absolute errors and changes with GNC over breast imaging positions. RESULTS:
      Phantom ADC errors varied with region of interest (ROI) position and scanner
      configuration; the mean error by configuration ranged from 1.4% to 19.9%. GNC
      significantly reduced the overall mean error for all sites from 9.9% to 0.6% (P =
      0.016). Spatial dependence of GNC was highest in the right-left (RL) and anterior
      posterior (AP) directions. Human subject mean tumor ADC was reduced 0.2 to 12% by
      GNC at different sites. By regression, every 1-cm change in tumor ROI position
      between baseline and follow-up visits resulted in an estimated change of 2.4% in
      the ADC early-treatment response measurement. CONCLUSION: GNC is effective for
      removing large, system-dependent errors in quantitative breast DWI. GNC may be
      important in ensuring reproducibility in multicenter studies and in reducing
      errors in longitudinal treatment response measures arising from spatial
      variations in tumor position between visits.

PMID- 25758544
TI  - Drugs for ADHD.

PMID- 25758545
TI  - VEGF inhibitors for AMD and diabetic macular edema.

PMID- 25758546
TI  - In brief: lisdexamfetamine (Vyvanse) for binge eating disorder.

PMID- 25758547
TI  - A powerful approach to test an optimally weighted combination of rare variants in
      admixed populations.
AB  - Population stratification has long been recognized as an issue in genetic
      association studies because unrecognized population stratification can lead to
      both false-positive and false-negative findings and can obscure true association
      signals if not appropriately corrected. This issue can be even worse in rare
      variant association analyses because rare variants often demonstrate stronger and
      potentially different patterns of stratification than common variants. To correct
      for population stratification in genetic association studies, we proposed a novel
      method to Test the effect of an Optimally Weighted combination of variants in
      Admixed populations (TOWA) in which the analytically derived optimal weights can
      be calculated from existing phenotype and genotype data. TOWA up weights rare
      variants and those variants that have strong associations with the phenotype.
      Additionally, it can adjust for the direction of the association, and allows for
      local ancestry difference among study subjects. Extensive simulations show that
      the type I error rate of TOWA is under control in the presence of population
      stratification and it is more powerful than existing methods. We have also
      applied TOWA to a real sequencing data. Our simulation studies as well as real
      data analysis results indicate that TOWA is a useful tool for rare variant
      association analyses in admixed populations. 

PMID- 25758548
TI  - Factors related to self-reported health status in low income midlife women.
AB  - Transition throughout midlife can affect women's perception of their health
      status. Multiple factors are potentially related to self-reported health status
      (SRHS), but it was not clear what factors are related to SRHS for midlife women,
      especially those with low income. This study examined factors related to SRHS in
      low income midlife women over time. A multi-step linear regression of
      longitudinal Medicaid Managed Care (MMC) data (n = 310) from July 2000 through
      November 2006 was used. Participants completed SRHS at initial (baseline)
      enrollment into MMC (T1), with a second assessment completed 11 to 23 months
      later for those retaining MMC eligibility (T2). Results indicated that disability
      and number of medical conditions were the factors most related to SRHS. SRHS
      scores differed significantly between non-disabled and disabled women. For
      disabled women, SRHS improved significantly between T1 and T2 (p < .001), but not
      for non-disabled women. Those with lower SRHS scores used community agencies more
      often. Further studies of SRHS and health-related factors are needed as SRHS is
      frequently an indicator of population health. Greater evidenced-based knowledge
      of SRHS in midlife women will inform preventive interventions for this
      population. 

PMID- 25758549
TI  - Rate and predictors of non-response to first-line antipsychotic treatment in
      first-episode schizophrenia.
AB  - OBJECTIVE: The goals of this study were to (i) estimate the rate of non-response
      to first-line treatment in first-episode schizophrenia, (ii) evaluate other
      outcomes associated with symptom non-response and (iii) identify demographic,
      baseline clinical and early treatment response predictors of non-response.
      METHODS: This was a single-site, longitudinal cohort study assessing the effects
      of treatment with flupenthixol decanoate according to a standardised protocol
      over 12 months in patients with schizophrenia, schizophreniform and schizo
      affective disorders. RESULTS: Of 126 patients who received at least one dose of
      study medication, 84 (67%) completed the study. Fifteen (12%) met our predefined
      criteria for non-response. Non-responders were younger and at baseline had more
      prominent disorganised symptoms, poorer social and occupational functioning,
      poorer quality of life for psychological, social and environmental domains, more
      prominent neurological soft signs (NSS) and lower body mass index. At endpoint,
      the non-responders were characterised by higher levels of symptomatology in all
      domains, poorer functional outcome, poorer quality of life and greater cognitive
      impairments. They also had more prominent NSS and lower body mass index. The
      strongest predictors of non-response were more prominent baseline NSS and poor
      early (7 weeks) treatment response. CONCLUSIONS: Results are consistent with a
      lower rate of refractoriness to treatment in first-episode schizophrenia compared
      with multi-episode samples.

PMID- 25758550
TI  - Peripheral nervous system involvement in chronic spinal cord injury.
AB  - INTRODUCTION: Upper motor neuron disorders are believed to leave the peripheral
      nervous system (PNS) intact. In this study we examined whether there is evidence
      of PNS involvement in spinal cord injury (SCI). METHODS: Twelve subjects with
      chronic low cervical or thoracic SCI were included prospectively. Needle
      electromyography was done in 10 different muscles in each subject bilaterally.
      Nerve conduction studies (NCS) were conducted in the fibular, tibial, and femoral
      motor and fibular and sural sensory nerves. RESULTS: Half the subjects had
      widespread abnormal spontaneous activity (SA), and the amount of SA correlated
      inversely with reflex activity and nerve length. Fibular nerve entrapment across
      the knee was seen in 6 subjects, and sciatic nerve entrapment was seen in 1.
      Apart from entrapment neuropathies, NCS changes were found predominantly in motor
      nerves. CONCLUSION: The presence of widespread electrophysiologic changes outside
      entrapment sites indicates that SCI has a significant impact on the entire PNS,
      affecting the motor part predominantly.

PMID- 25758551
TI  - Epileptic headache: need for a better knowledge--a response.

PMID- 25758552
TI  - Post-traumatic neurodegeneration and chronic traumatic encephalopathy.
AB  - Traumatic brain injury (TBI) is a leading cause of mortality and morbidity around
      the world. Concussive and subconcussive forms of closed-head injury due to impact
      or blast neurotrauma represent the most common types of TBI in civilian and
      military settings. It is becoming increasingly evident that TBI can lead to
      persistent, long-term debilitating effects, and in some cases, progressive
      neurodegeneration and chronic traumatic encephalopathy (CTE). The epidemiological
      literature suggests that a single moderate-to-severe TBI may be associated with
      accelerated neurodegeneration and increased risk of Alzheimer's disease,
      Parkinson's disease, or motor neuron disease. However, the pathologic phenotype
      of these post-traumatic neurodegenerations is largely unknown and there may be
      pathobiological differences between post-traumatic disease and the corresponding
      sporadic disorder. By contrast, the pathology of CTE is increasingly well known
      and is characterized by a distinctive pattern of progressive brain atrophy and
      accumulation of hyperphosphorylated tau neurofibrillary and glial tangles,
      dystrophic neurites, 43 kDa TAR DNA-binding protein (TDP-43) neuronal and glial
      aggregates, microvasculopathy, myelinated axonopathy, neuroinflammation, and
      white matter degeneration. Clinically, CTE is associated with behavioral changes,
      executive dysfunction, memory deficits, and cognitive impairments that begin
      insidiously and most often progress slowly over decades. Although research on the
      long-term effects of TBI is advancing quickly, the incidence and prevalence of
      post-traumatic neurodegeneration and CTE are unknown. Critical knowledge gaps
      include elucidation of pathogenic mechanisms, identification of genetic risk
      factors, and clarification of relevant variables-including age at exposure to
      trauma, history of prior and subsequent head trauma, substance use, gender,
      stress, and comorbidities-all of which may contribute to risk profiles and the
      development of post-traumatic neurodegeneration and CTE. This article is part of
      a Special Issue entitled 'Traumatic Brain Injury'.

PMID- 25758553
TI  - Proteomic identification of nuclear processes manipulated by cytomegalovirus
      early during infection.
AB  - Human cytomegalovirus (HCMV) is a herpesvirus that is ubiquitously distributed
      worldwide and causes life-threating disease upon immunosuppression. HCMV
      expresses numerous proteins that function to establish an intracellular
      environment that supports viral replication. Like most DNA viruses, HCMV
      manipulates processes within the nucleus. We have quantified changes in the host
      cell nuclear proteome at 24 h post infection following infection with a clinical
      viral isolate. We have combined SILAC with multiple stages of fractionation to
      define changes. Tryptic peptides were analyzed by RP-HPLC combined with LC-MS/MS
      on an LTQ Orbitrap Velos mass spectrometer. Data from three biological replicates
      were processed with MaxQuant. A total of 1281 cellular proteins were quantified
      and 77 were found to be significantly differentially expressed. In addition, we
      observed 36 viral proteins associated with the nucleus. Diverse biological
      processes were significantly altered, including increased aspects of cell
      cycling, mRNA metabolism, and nucleocytoplasmic transport and decreased immune
      responses. We validated changes for several proteins including a subset of
      classical nuclear transport proteins. In addition, we demonstrated that
      disruption of these import factors is inhibitory to HCMV replication. Overall, we
      have identified HCMV-induced changes in the nuclear proteome and uncovered
      several processes that are important for infection. All MS data have been
      deposited in the ProteomeXchange with identifier PXD001909
      (http://proteomecentral.proteomexchange.org/dataset/PXD001909). 

PMID- 25758554
TI  - Survival of a surgical series of lung cancer patients with synchronous multiple
      ground-glass opacities, and the management of their residual lesions.
AB  - OBJECTIVES: We reviewed the medical record of a series of patients with
      synchronous multiple lung cancers (SMLC), in an attempt to identify the optimal
      treatment strategy for multiple ground-glass opacities (GGOs). MATERIALS AND
      METHODS: From 2004 to 2010, 1223 patients underwent complete resection of non
      small cell lung cancer. Among these, there were 67 patients (5.5%) with SMLC with
      at least 1 of the nodules showing GGO appearance. SMLC was divided into the main
      cancer (MC) which was a main target based on its tumor size or radiological
      invasiveness and sub-nodules. According to consolidation/tumor ratio (CTR) on
      thin-section computed tomography, 67 cases were classified into GG-group (MC
      showing GGO-dominant lesion; CTR<=0.5) and GS-group (MC showing solid-dominant
      lesion; CTR>0.5). RESULTS: There were 24 patients in the GG-group (36%) and 43
      patients in the GS-group (64%). Surgical resections included 11 sublobar
      resections (SLs), 32 lobectomies, 19 lobectomy+SLs, and 4 bilobectomies. There
      were 39 patients with a total of 118 unresected GGOs after the initial surgery.
      Among them, the frequency of growth was 8% on a per-nodule basis with the median
      tumor doubling time of 1373 days, and new GGOs emerged in 15 patients (23%).
      Multivariate analysis demonstrated that larger size of MC and the GS-group was
      associated with poor prognosis, whereas growth of the residual GGOs, the
      development of new GGOs, or whether or not all GGOs were treated did not affect
      survival. The 5-year OS proportions were 95.8% for the GG-group and 68.0% for the
      GS-group (p=0.009), and 92.4% for a MC of <=25 mm and 53.6% for a MC of >25 mm
      (p=0.008). CONCLUSION: Survival of patients with multifocal GGOs is strongly
      affected by radiological findings of the MC. Strict surgical control for MC could
      be most important.

PMID- 25758555
TI  - Identification of biomarkers for the detection of early stage lung adenocarcinoma
      by microarray profiling of long noncoding RNAs.
AB  - BACKGROUND: Lung adenocarcinoma has one of the poorest outcomes of any cancer
      worldwide, in part due to the lack of a reliable means of early detection. Long
      noncoding RNAs (lncRNAs) have been shown to be deregulated in some types of
      cancer; however, the contributions of lncRNAs to lung adenocarcinoma remain
      unknown. METHODS: We described the expression profile of lncRNAs in human lung
      adenocarcinoma at an early stage and the corresponding adjacent nontumorous
      tissues (NT) by microarray. From the microarray analysis, a total of 1170 lncRNAs
      were significantly differentially expressed in three early stage lung
      adenocarcinoma tissues compared with NT (fold-change>=2.0, p<=0.05). Candidate
      biomarkers were selected from the significantly differentially expressed lncRNAs
      based on our established filtering pipeline; subsequently, marker optimization
      and validation by reverse transcription quantitative real-time polymerase chain
      reaction (RT-qPCR) on a total of 102 pairs of early stage lung adenocarcinoma and
      NT samples. RESULTS: A panel of 5-lncRNA was identified that could distinguish
      early stage lung adenocarcinoma from NT samples with high sensitivity and
      specificity. The area under the receiver operating characteristic curve (AUC) for
      tumor identification in the training and validation sets were 0.978 and 0.987,
      respectively. CONCLUSIONS: Our results are the first to reveal differentially
      expressed lncRNAs in early stage lung adenocarcinoma and suggest that lncRNAs may
      be novel candidate biomarkers for the early detection of this disease.

PMID- 25758556
TI  - Final results from a Phase II study of pemetrexed and cisplatin with concurrent
      thoracic radiation after Pem-Cis induction in patients with unresectable locally
      advanced non-squamous non-small cell lung cancer (NSCLC).
AB  - OBJECTIVES: This single-arm multicenter Phase II study investigated the efficacy
      and safety of pemetrexed (Pem) and cisplatin (Cis) induction chemotherapy (CT)
      followed by full-dose Pem-Cis plus concurrent radiotherapy (RT) in patients with
      locally advanced non-squamous NSCLC. MATERIALS AND METHODS: Patients with
      unresectable Stage III non-squamous NSCLC received two 21-day cycles of Pem 500
      mg/m(2) (vitamin/folic acid supplementation and dexamethasone prophylaxis per Pem
      label)+Cis 75 mg/m(2) on Day 1. Eligible patients who had not progressed
      continued with 2 further cycles of full-dose Pem-Cis plus concurrent RT (2
      Gy/fraction, 5 days/week, 66 Gy total). Primary endpoint was the 1-year
      progression-free survival (PFS) rate. RESULTS: Of 90 patients enrolled (all
      treated; median age 61 years, male/female 57%/43%, ECOG performance status 0/1
      66%/34%, adenocarcinoma 90%, Stage III 36%/62%), 75 (83%) completed induction CT
      and started concurrent CT+RT. 64 (71%) patients received all 4 CT cycles and an
      RT dose >=60 Gy. The 1-year PFS rate was 51.3% (95%CI: 42.0, 60.5). Median PFS
      was 10.6 months (95%CI: 8.6, 17.3), median OS was 26.2 months (95%CI: 16.7, not
      estimable). One patient died from enteritis (treatment-related) during Cycle 4.
      Four patients discontinued due to treatment-related adverse events, 1 on
      induction CT (renal failure), 3 on concurrent CT+RT (1 hypoacusis, 2 acute
      esophagitis). During induction CT, 18.9% of patients reported Grade 3/4 CTCAEs,
      only neutropenia (2.2%) and syncope (2.2%) were reported by >1 patient. During
      concurrent CT+RT, 41.3% of patients reported G3/4 CTCAEs, mainly esophagitis
      (12.0%), neutropenia (10.7%), and leukopenia (9.3%). CONCLUSION: In this study of
      Pem-Cis induction CT followed by full-dose Pem-Cis with concurrent RT, median PFS
      was 10.6 months and toxicity was manageable, in line with previous data on Pem
      Cis plus RT.

PMID- 25758557
TI  - Increased protein intake is associated with uncontrolled blood pressure by 24
      hour ambulatory blood pressure monitoring in patients with type 2 diabetes.
AB  - OBJECTIVE: To analyze possible associations of dietary components, especially
      protein intake, with blood pressure (BP) during ambulatory BP monitoring (ABPM)
      in patients with type 2 diabetes. METHODS: In this cross-sectional study, BP of
      outpatients with type 2 diabetes was evaluated by 24-hour ABPM (Spacelabs 90207)
      and usual diet by 3-day weighed diet records. Patients were divided into 2 groups
      according to their daytime ABPM: uncontrolled BP (systolic BP >= 135 mmHg or
      diastolic BP >= 85 mmHg) and controlled BP (systolic BP < 135 mmHg and diastolic
      BP < 85 mmHg). Logistic regression models unadjusted and adjusted for possible
      confounders (covariates) were used to analyze the association of protein and
      uncontrolled BP. RESULTS: A total of 121 patients with type 2 diabetes aged 62.3
      years, 54.5% of whom were women, were studied. The uncontrolled BP group had
      higher glycated hemoglobin (HbA1C) values (8.4 +/- 2.0 vs 7.6 +/- 1.3%; p = 0.04)
      and consumed more protein (20.0 +/- 3.8 vs 18.2 +/- 3.6% of energy; p = 0.01) and
      meat, (2.6 [1.45, 2.95] vs 2.0 [1.49, 2.90] g/kg weight; p = 0.04) than the
      controlled BP group. In a multivariate analysis, protein intake (% of energy)
      increased the chance for uncontrolled BP (odds ratio [OR] = 1.16; 95% confidence
      interval [CI], 1.02, 1.30; p = 0.02), adjusted for body mass index (BMI), HbA1C,
      low-density lipoprotein (LDL) cholesterol, number of antihypertensive
      medications, and ethnicity. Meat consumption higher than 3.08 g/kg weight/day
      more than doubled the chance for uncontrolled BP (OR = 2.53; 95% CI, 1.01, 7.60;
      p = 0.03). CONCLUSION: High protein intake and meat consumption were associated
      with high daytime ABPM values in patients with type 2 diabetes. Reducing meat
      intake might represent an additional dietary intervention in hypertensive
      patients with type 2 diabetes.

PMID- 25758558
TI  - Spondylodiscitis after sacrocolpopexy.

PMID- 25758559
TI  - Severe hyperemesis gravidarum associated with gestational thyrotoxicosis and
      acute biliary pancreatitis.

PMID- 25758560
TI  - Do we sometimes see too much? Prenatal diagnosis of a true umbilical cord knot.

PMID- 25758561
TI  - Response to "importance of accurate statistical analysis of experimental studies
      using laboratory animal models".

PMID- 25758562
TI  - A nationwide survey of hereditary angioedema due to C1 inhibitor deficiency in
      Italy.
AB  - INTRODUCTION: Hereditary angioedema due to C1-inhibitor deficiency (C1-INH-HAE
      type I) or dysfunction (C1-INH-HAE type II) is a rare disease characterized by
      recurrent episodes of edema with an estimated frequency of 1:50,000 in the global
      population without racial or gender differences. In this study we present the
      results of a nationwide survey of C1-INH-HAE patients referring to 17 Italian
      centers, the Italian network for C1-INH-HAE, ITACA. METHODS: Italian patients
      diagnosed with C1-INH-HAE from 1973 to 2013 were included in the study. Diagnosis
      of C1-INH-HAE was based on family and/or personal history of recurrent angioedema
      without urticaria and on antigenic and/or functional C1-INH deficiency. RESULTS:
      983 patients (53% female) from 376 unrelated families were included in this
      survey. Since 1973, 63 (6%) patients diagnosed with C1-INH-HAE died and data from
      3 patients were missing when analysis was performed. Accordingly, the minimum
      prevalence of HAE in Italy in 2013 is 920:59,394,000 inhabitants, equivalent to
      1:64,935. Compared to the general population, patients are less represented in
      the early and late decades of life: men start reducing after the 5(th) decade and
      women after the 6(th). Median age of patients is 45 (IQ 28-57), median age at
      diagnosis is 26 years (IQ 13-41). C1-INH-HAE type 1 are 87%, with median age at
      diagnosis of 25 (13-40); type 2 are 13% with median age at diagnosis of 31 (IQ 16
      49). Functional C1INH is <=50% in 99% of patients. Antigen C1INH is <=50% in 99%
      of type 1. C4 is <=50% in 96% of patients. The chance of having C1-INH-HAE with
      C4 plasma levels >50% is < 0.05. CONCLUSION: This nationwide survey of C1-INH-HAE
      provides for Italy a prevalence of 1:64,935. C1-INH-HAE patients listed in our
      database have a shorter life expectancy than the general population. An increased
      awareness of the disease is needed to reduce this discrepancy. Measurement of C4
      antigen can exclude diagnosis of C1-INH-HAE with an accuracy > 95%. This
      parameter should be therefore considered for initial screening in differential
      diagnosis of angioedema.

PMID- 25758563
TI  - LINGO-1 promotes lysosomal degradation of amyloid-beta protein precursor.
AB  - Sequential proteolytic cleavages of amyloid-beta protein precursor (AbetaPP) by
      beta-secretase and gamma-secretase generate amyloid beta (Abeta) peptides, which
      are thought to contribute to Alzheimer's disease (AD). Much of this processing
      occurs in endosomes following endocytosis of AbetaPP from the plasma membrane.
      However, this pathogenic mode of processing AbetaPP may occur in competition with
      lysosomal degradation of AbetaPP, a common fate of membrane proteins trafficking
      through the endosomal system. Following up on published reports that LINGO-1
      binds and promotes the amyloidogenic processing of AbetaPP we have examined the
      consequences of LINGO-1/AbetaPP interactions. We report that LINGO-1 and its
      paralogs, LINGO-2 and LINGO-3, decrease processing of AbetaPP in the
      amyloidogenic pathway by promoting lysosomal degradation of AbetaPP. We also
      report that LINGO-1 levels are reduced in AD brain, representing a possible
      pathogenic mechanism stimulating the generation of Abeta peptides in AD. 

PMID- 25758564
TI  - Sorting of Double-Walled Carbon Nanotubes According to Their Outer Wall
      Electronic Type via a Gel Permeation Method.
AB  - In this work, we demonstrate the application of the gel permeation technique to
      the sorting of double-walled carbon nanotubes (DWCNTs) according to their outer
      wall electronic type. Our method uses Sephacryl S-200 gel and yields sorted
      fractions of DWCNTs with impurities removed and highly enriched in nanotubes with
      either metallic (M) or semiconducting (S) outer walls. The prepared fractions are
      fully characterized using optical absorption spectroscopy, transmission electron
      microscopy, and atomic force microscopy, and the entire procedure is monitored in
      real time using process Raman analysis. The sorted DWCNTs are then integrated
      into single nanotube field effect transistors, allowing detailed electronic
      measurement of the transconductance properties of the four unique inner@outer
      wall combinations of S@S, S@M, M@S, and M@M. 

PMID- 25758565
TI  - Long term impact of antiretroviral therapy--can we end HIV epidemic, the goal
      beyond 2015.

PMID- 25758566
TI  - After 3 decades of paediatric HIV/AIDS--where do we stand?

PMID- 25758567
TI  - Addressing tobacco use & dependence in primary care: a priority for tobacco
      control in the country.

PMID- 25758568
TI  - Spectrum of Hashimoto's thyroiditis: clinical, biochemical & cytomorphologic
      profile.

PMID- 25758569
TI  - An insight into the understanding of 5-HTR2A variants leading to schizophrenia.

PMID- 25758570
TI  - Current concepts on magnetic resonance imaging (MRI) perfusion-diffusion
      assessment in acute ischaemic stroke: a review & an update for the clinicians.
AB  - Recently, several medical societies published joint statements about imaging
      recommendations for acute stroke and transient ischaemic attack patients. In
      following with these published guidelines, we considered it appropriate to
      present a brief, practical and updated review of the most relevant concepts on
      the MRI assessment of acute stroke. Basic principles of the clinical
      interpretation of diffusion, perfusion, and MRI angiography (as part of a global
      MRI protocol) are discussed with accompanying images for each sequence. Brief
      comments on incidence and differential diagnosis are also included, together with
      limitations of the techniques and levels of evidence. The purpose of this article
      is to present knowledge that can be applied in day-to-day clinical practice in
      specialized stroke units or emergency rooms to attend patients with acute
      ischaemic stroke or transient ischaemic attack according to international
      standards. 

PMID- 25758571
TI  - Clinical, biochemical & cytomorphologic study on Hashimoto's thyroiditis.
AB  - BACKGROUND & OBJECTIVES: Despite, the extensive salt iodization programmes
      implemented in India, the prevalence of goiter has not reduced much in our
      country. The most frequent cause of hypothyroidism and goiter in iodine
      sufficient areas is Hashimoto's thyroiditis (HT). This study records the clinical
      presentation, biochemical status, ultrasonographic picture and cytological
      appearance of this disease in a coastal endemic zone for goiter. METHODS: Case
      records of patients with cytological diagnosis of HT were studied in detail, with
      reference to their symptoms, presence of goiter, thyroid function status,
      antibody levels and ultrasound picture. Detailed cytological study was conducted
      in selected patients. RESULTS: A total of 144 patients with cytological proven
      HT/lymphocytic thyroiditis were studied. Ninety per cent of the patients were
      females and most of them presented within five years of onset of symptoms. Sixty
      eight per cent patients had diffuse goiter, 69 per cent were clinically euthyroid
      and 46 per cent were biochemically mildly hypothyroid. Antibody levels were
      elevated in 92.3 per cent cases. In majority of patients the sonographic picture
      showed heterogeneous echotexture with increased vascularity. Cytological changes
      were characteristic. INTERPRETATION & CONCLUSIONS: Our study showed predominance
      of females in the study population in 21-40 yr age group with diffuse goiter. We
      suggest that in an endemic zone for goiter, all women of the child bearing age
      should be screened for HT.

PMID- 25758572
TI  - 5-Hydroxytryptamine (serotonin) 2A receptor gene polymorphism is associated with
      schizophrenia.
AB  - BACKGROUND & OBJECTIVES: Schizophrenia, the debilitating neuropsychiatric
      disorder, is known to be heritable, involving complex genetic mechanisms. Several
      chromosomal regions associated with schizophrenia have been identified during the
      past; putative gene (s) in question, to be called the global signature for the
      pathophysiology of the disease, however, seems to evade us. The results obtained
      from the several population-wise association-non association studies have been
      diverse. w0 e therefore, undertook the present study on Tamil speaking population
      in south India to examine the association between the single nucleotide
      polymorphisms (SNPs) at the serotonin receptor gene (5HT2A) and the occurrence of
      the disease. METHODS: Blood samples collected from 266 cases and 272 controls
      were subjected to genotyping (PCR amplification of candidate SNPs, RFLP and
      sequencing). The data on the SNPs were subjected to statistical analysis for
      assessing the gene frequencies in both the cases and the controls. RESULTS: The
      study revealed significant association between the genotypic frequencies of the
      serotonin receptor polymorphism and schizophrenia. SNP analysis revealed that the
      frequencies of GG (30%, rs6311) and CC genotypes (32%, rs6313), were higher in
      patients (P<0.05) than in controls. The study also showed presence of G and C
      alleles in patients. s0 ignificant levels of linkage disequilibrium (LD) were
      found to exist between the genotype frequencies of rs6311 and rs6313.
      INTERPRETATION & CONCLUSIONS: This study indicated an association between the
      SNPs (rs6311 and rs6313) of the serotonin receptor 5HT2A and schizophrenia.
      HapMap analysis revealed that in its genotype distribution, the Tamil speaking
      population was different from several other populations across the world,
      signifying the importance of such ethnicity-based studies to improve our
      understanding of this complex disease.

PMID- 25758573
TI  - Expression profile of mitrogen-activated protein kinase (MAPK) signaling genes in
      the skeletal muscle & liver of rat with type 2 diabetes: role in disease
      pathology.
AB  - BACKGROUND & OBJECTIVES: Type 2 diabetes (T2D) is characterized as hyperglycaemia
      caused by defects in insulin secretion, and it affects target tissues, such as
      skeletal muscle, liver and adipose tissue. Therefore, analyzing the changes of
      gene expression profiles in these tissues is important to elucidate the
      pathogenesis of T2D. We, therefore, measured the gene transcript alterations in
      liver and skeletal muscle of rat with induced T2D, to detect differentially
      expressed genes in liver and skeletal muscle and perform gene-annotation
      enrichment analysis. METHODS: In the present study, skeletal muscle and liver
      tissue from 10 streptozotocin-induced diabetic rats and 10 control rats were
      analyzed using gene expression microarrays. KEGG pathways enriched by
      differentially expressed genes (DEGs) were identified by WebGestalt Expander and
      GATHER software. DEGs were validated by the method of real-time PCR and western
      blot. RESULTS: From the 9,929 expressed genes across the genome, 1,305 and 997
      differentially expressed genes (DEGs, P<0.01) were identified in comparisons of
      skeletal muscle and liver, respectively. Large numbers of DEGs (200) were common
      in both comparisons, which was clearly more than the predicted number (131 genes,
      P<0.001). For further interpretation of the gene expression data, three over
      representation analysis softwares (WebGestalt, Expander and GATHER) were used.
      All the tools detected one KEGG pathway (MAPK signaling) and two GO (gene
      ontology) biological processes (response to stress and cell death), with
      enrichment of DEGs in both tissues. In addition, PPI (protein-protein
      interaction) networks constructed using human homologues not only revealed the
      tendency of DEGs to form a highly connected module, but also suggested a "hub"
      role of p38-MAPK-related genes (such as MAPK14) in the pathogenesis of T2D.
      INTERPRETATION & CONCLUSIONS: Our results indicated the considerably aberrant
      MAPK signaling in both insulin-sensitive tissues of T2D rat, and that the p38 may
      play a role as a common "hub" in the gene module response to hyperglycaemia.
      Furthermore, our research pinpoints the role of several new T2D-associated genes
      (such as Srebf1 and Ppargc1) in the human population.

PMID- 25758574
TI  - Hypobaric hypoxia-mediated protein expression in plasma of susceptible & tolerant
      rats.
AB  - BACKGROUND & OBJECTIVES: Low availability of oxygen at high altitudes has a great
      impact on the human life processes. There is a widespread interest and need to
      find out protein(s) that are possibly involved in mediating tolerance to
      hypobaric hypoxia. We undertook this study to identify and characterize protein
      expression in plasma of hypoxia susceptible and tolerant rats. METHODS: Male
      albino Sprague Dawley rats were segregated into susceptible and tolerant groups
      on the basis of their gasping time when exposed to simulated hypobaric hypoxia of
      32,000 ft (9,754 m) at 32 degrees C. Comparative proteome profiling of blood
      plasma of hypoxia susceptible and tolerant individuals was performed using 2
      dimentional (2-D) gel electrophoresis. RESULTS: Three proteins with higher
      expression levels were selected separately from tolerant and susceptible samples.
      Characterization of these proteins from tolerant sample using MALDI-TOF/TOF and
      MASCOT search indicated their homology with two different super-families viz.
      NADB-Rossmann superfamily (Rab GDP dissociation inhibitor beta) and Transferrin
      superfamily (two Serotransferrins), having potential role in imparting tolerance
      against hypoxia. Three high level upregulated proteins were characterized from
      blood plasma of hypoxia susceptible animals showing similarity with threonine
      tRNA ligase (mitochondrial), carbohydrate sulphotransferase 7 and aspartate tRNA
      ligase (cytoplasmic) that play a role in ATP binding, carbohydrate metabolism and
      protein biosynthesis, respectively. INTERPRETATION & CONCLUSIONS: Our results
      indicated that rats segregated into hypoxia sensitive and tolerant based on their
      gasping time showed differential expression of proteins in blood plasma.
      Characterization of these differentially expressed proteins will lead to better
      understanding of molecular responses occurring during hypoxia and subsequently
      development of biomarkers for categorization of hypoxia susceptible and tolerant
      individuals.

PMID- 25758575
TI  - Antigen sequence typing of outer membrane protein (fetA) gene of Neisseria
      meningitidis serogroup A from Delhi & adjoining areas.
AB  - BACKGROUND & OBJECTIVES: Meningitis caused by Neisseria meningitidis is a fatal
      disease. Meningococcal meningitis is an endemic disease in Delhi and irregular
      pattern of outbreaks has been reported in India. All these outbreaks were
      associated with serogroup A. Detailed molecular characterization of N.
      meningitidis is required for the management of this fatal disease. In this study,
      we characterized antigenic diversity of surface exposed outer membrane protein
      (OMP) FetA antigen of N. meningitidis serogroup A isolates obtained from cases of
      invasive meningococcal meningitis in Delhi, India. METHODS: Eight isolates of N.
      meningitidis were collected from cerebrospinal fluid during October 2008 to May
      2011 from occasional cases of meningococcal meningitis. Seven isolates were from
      outbreaks of meningococcal meningitis in 2005-2006 in Delhi and its adjoining
      areas. These were subjected to molecular typing of fetA gene, an outer membrane
      protein gene. RESULTS: All 15 N. meningitides isolates studied were serogroup A.
      This surface exposed porin is putatively under immune pressure. Hence as a part
      of molecular characterization, genotyping was carried out to find out the
      diversity in outer membrane protein (FetA) gene among the circulating isolates of
      N. meningitidis. All 15 isolates proved to be of the same existing allele type of
      FetA variable region (VR) when matched with global database. The allele found was
      F3-1 for all the isolates. INTERPRETATION & CONCLUSIONS: There was no diversity
      reported in the outer membrane protein FetA in the present study and hence this
      protein appeared to be a stable molecule. More studies on molecular
      characterization of FetA antigen are required from different serogroups
      circulating in different parts of the world.

PMID- 25758576
TI  - MALDI-TOF mass spectrometry proteomic based identification of clinical bacterial
      isolates.
AB  - BACKGROUND & OBJECTIVES: Pathogenic bacteria often cause life threatening
      infections especially in immunocompromised individuals. Therefore, rapid and
      reliable species identification is essential for a successful treatment and
      disease management. We evaluated a rapid, proteomic based technique for
      identification of clinical bacterial isolates by protein profiling using matrix
      assisted laser desorption-ionization time - of - flight mass spectrometry (MALDI
      TOF MS). METHODS: Freshly grown bacterial isolates were selected from culture
      plates. Ethanol/formic acid extraction procedure was carried out, followed by
      charging of MALDI target plate with the extract and overlaying with alpha-cyano-4
      hydroxy-cinnamic acid matrix solution. Identification was performed using the
      MALDI BioTyper 1.1, software for microbial identification (Bruker Daltonik GmbH,
      Bremen, Germany). RESULTS: A comparative analysis of 82 clinical bacterial
      isolates using MALDI -TOF MS and conventional techniques was carried out. Amongst
      the clinical isolates, the accuracy at the species level for clinical isolates
      was 98.78%. One out of 82 isolates was not in accordance with the conventional
      assays because MALDI-TOF MS established it as Streptococcus pneumoniae and
      conventional methods as Streptococcus viridans. INTERPRETATION & CONCLUSIONS:
      MALDI - TOF MS was found to be an accurate, rapid, cost-effective and robust
      system for identification of clinical bacterial isolates. This innovative
      approach holds promise for earlier therapeutic intervention leading to better
      patient care.

PMID- 25758577
TI  - Characterization of Shiga-toxigenic Escherichia coli isolated from cases of
      diarrhoea & haemolytic uremic syndrome in north India.
AB  - BACKGROUND & OBJECTIVES: Shiga toxin producing Escherichia coli (STEC) is an
      important zoonotic foodborne pathogen, capable of causing haemorrhagic colitis
      (HC) and haemolytic uremic syndrome (HUS). As data from India on human infections
      caused by STEC are limited, this study was carried out for hospital based
      surveillance for STEC as a causative agent of diarrhoea, bloody diarrhoea and HUS
      at a tertiary care centre and to study the virulence gene profile and strain
      relatedness by multi locus variable tandem repeat analysis (MLVA). METHODS: A
      total of 600 stool samples were studied. Stool samples of every fifth patient
      presenting with non-bloody diarrhoea, all cases of bloody diarrhoea and diarrhoea
      associated HUS (D+HUS) were collected from October 2009 to September 2011. Stool
      samples were cultured for STEC and characterization of STEC was done by
      serogrouping, virulence genes analysis, and MLVA typing. RESULTS: STEC were
      isolated as a sole pathogen from 11 stool samples [5 of 290 (1.7%) non-blood
      diarrhoea and 5 of 300 (1.6%) blood diarrhoea cases]. STEC was also isolated from
      one fatal case of HUS who was an eight month old child. Only six of 11 isolates
      were positive for stx2 gene, whereas stx1 was present in all 11 isolates. Only
      one isolate was positive for eae. Other adhesion genes present were iha in five
      isolates, followed by toxB and efa1 in two each and saa gene in one, isolate.
      Among the plasmid encoded genes, espP, hly and etpD were each present in one
      isolate each. In the MLVA typing, diverse profiles were obtained except two
      untypeable isolates from different patients shared the same MLVA profile. Both
      these isolates were not epidemiologically linked. INTERPRETATION & CONCLUSIONS:
      This study demonstrated that STEC could be a causative agent of diarrhoea, bloody
      diarrhoea and sporadic HUS. However, further work needs to be done to study and
      explore the prevalence of these organisms in the food chain in this region.

PMID- 25758578
TI  - Seroprevalence of coxiellosis (Q fever) in sheep & goat in Puducherry &
      neighbouring Tamil Nadu.

PMID- 25758579
TI  - Need for & use of guidelines for reporting qualitative research.

PMID- 25758580
TI  - Avoiding contamination in randomized controlled trial.

PMID- 25758581
TI  - Classical eschar in scrub typhus.

PMID- 25758582
TI  - Oculomotor nerve palsy in dengue encephalitis--a rare presentation.

PMID- 25758583
TI  - The impact of HIV on presentation and outcome of bacterial sepsis and other
      causes of acute febrile illness in Gabon.
AB  - PURPOSE: HIV, bacterial sepsis, malaria, and tuberculosis are important causes of
      disease in Africa. We aimed to determine the impact of HIV on the presentation,
      causes and outcome of bacterial sepsis and other acute febrile illnesses in
      Gabon, Central Africa. METHODS: We performed a prospective observational study in
      new adult admissions with fever or hypothermia (>= 38 or <36  degrees C). Blood
      cultures, as well as HIV and malaria testing were performed in all patients.
      RESULTS: We enrolled 382 patients, including 77 (20.2%) with HIV infection.
      Malaria was the most frequent diagnosis (n = 130, 34%), and was associated with a
      more severe presentation in HIV patients. Sepsis was also common (n = 107, 28%),
      including 29 (7.6%) patients with culture confirmed bacterial bloodstream
      infection. Bacterial bloodstream infections were more frequent in HIV patients,
      in particular with S. pneumoniae. Tuberculosis was observed in 29 (7.6%)
      patients, and was also more common in HIV patients. The majority of HIV patients
      was newly diagnosed, and only 15 (19.5%) were using combination antiretroviral
      therapy. CONCLUSIONS: Our findings illustrate the impact of HIV co-infection on
      the burden of sepsis, malaria and tuberculosis in Gabon, as well as the need to
      scale up HIV counseling, testing and treatment.

PMID- 25758584
TI  - A direct method to evaluate the time-dependent predictive accuracy for
      biomarkers.
AB  - Time-dependent receiver operating characteristic (ROC) curves and their area
      under the curve (AUC) are important measures to evaluate the prediction accuracy
      of biomarkers for time-to-event endpoints (e.g., time to disease progression or
      death). In this article, we propose a direct method to estimate AUC(t) as a
      function of time t using a flexible fractional polynomials model, without the
      middle step of modeling the time-dependent ROC. We develop a pseudo partial
      likelihood procedure for parameter estimation and provide a test procedure to
      compare the predictive performance between biomarkers. We establish the
      asymptotic properties of the proposed estimator and test statistics. A major
      advantage of the proposed method is its ease to make inference and to compare the
      prediction accuracy across biomarkers, rendering our method particularly
      appealing for studies that require comparing and screening a large number of
      candidate biomarkers. We evaluate the finite-sample performance of the proposed
      method through simulation studies and illustrate our method in an application to
      AIDS Clinical Trials Group 175 data. 

PMID- 25758585
TI  - Pediculicidal treatment using ethanol and Melia azedarach L.
AB  - Pediculosis is an infestation of the scalp caused by Pediculus humanus capitis,
      known as lice, which affects thousands of people throughout the world. Disease
      control is achieved by topical insecticides, whose indiscriminate use has led to
      the emergence of resistant populations of lice. Melia azedarach L. (Meliaceae) is
      an Asian tree that is found in Brazil, where it is popularly known as cinnamon or
      santa-barbara. This study aimed to evaluate a pediculicidal treatment, made from
      a hydroethanolic extract of M. azedarach, and to study the effect of extraction
      solvents (ethanol and water) on insect mortality. The chemical composition of
      crude extract was studied by gas chromatography, identifying 32 methyl esters of
      fatty acids, with esters of heneicosanoic, palmitic, and arachidic acids present
      in greatest abundance. The (1)H and (13)C nuclear magnetic resonance (NMR)
      spectra suggested the presence of flavonoids and terpenes. Quercetin-3-O-beta-D
      glucopyranoside (1) and quercetin-3-O-beta-D-glucopyranosyl-(1 -> 6)-O-beta-D
      glucopyranoside (2) were isolated from the extract. The bioassay of pediculicidal
      activity shows that the M. azedarach extract had a pediculicidal activity,
      inducing the death of all lice faster than 1% permethrin, a topical insecticide
      commonly used to control lice.

PMID- 25758586
TI  - Molecular characterization of Trichuris serrata.
AB  - Trichuris serrata, a whipworm of cats, can cause inflammation in the cecum and
      upper portion of the large intestine. It is unknown if the virulence and
      pathology of T. serrata differ from Trichuris campanula, the other species in
      cats. Distinguishing the species based on egg size is challenging. In addition,
      Trichuris eggs can be difficult to distinguish from Capillaria spp. This paper
      presents the first molecular description of T. serrata. The 18S ribosomal RNA
      (rRNA) gene was sequenced from male adult worms sourced from two unrelated cats
      on St. Kitts. Based on the analysis of 651 base pairs, T. serrata was found to be
      different than any other Trichuris species for which published sequencing of the
      18S rRNA gene is available. A dendrogram was developed using Molecular
      Evolutionary Genetics Analysis version 6.0, and evolutionary history was inferred
      using the minimum evolution method. T. serrata was found to be most closely
      related to Trichuris vulpis, the Trichuris of dogs. Further development of the
      methodology could enable distinguishing T. serrata, T. campanula, and Capillaria
      spp. infections in cats and aid in diagnosis. 

PMID- 25758587
TI  - Diphyllobothrium nihonkaiense: wide egg size variation in 32 molecularly
      confirmed adult specimens from Korea.
AB  - The eggs of Diphyllobothrium nihonkaiense were reported to be smaller than those
      of the classical Diphyllobothrium latum in general. However, verification using a
      large number of adult tapeworms is required. We assessed the egg size variation
      in 32 adult specimens of D. nihonkaiense recovered from Korean patients in 1975
      2014. The diagnosis of individual specimens was based on analysis of the
      mitochondrial cytochrome c oxidase 1 gene sequence. Uterine eggs (n = 10) were
      obtained from each specimen, and their length and width were measured by
      micrometry. The results indicated that the egg size of D. nihonkaiense (total
      number of eggs measured, 320) was widely variable according to individual
      specimens, 54-76 MUm long (mean 64) and 35-58 MUm wide (mean 45), with a length
      width ratio of 1.32-1.70 (mean 1.46). The worm showing the smallest egg size had
      a length range of 54-62 MUm, whereas the one showing the largest egg size had a
      length range of 68-76 MUm. The two ranges did not overlap, and a similar pattern
      was observed for the egg width. Mapping of each egg size (n = 320) showed a wide
      variation in length and width. The widely variable egg size of D. nihonkaiense
      cannot be used for specific diagnosis of diphyllobothriid tapeworm infections in
      human patients.

PMID- 25758588
TI  - Biochemical and functional characterization of the glutathione S-transferase from
      Trichinella spiralis.
AB  - Glutathione-S-transferase (GST) is a family of multifunctional enzymes catalyzing
      detoxification reactions. Our previous study showed that Trichinella spiralis GST
      (TsGST) gene is an up-regulated gene in intestinal infective larvae (IIL)
      compared to muscle larvae (ML) and vaccination of mice with rTsGST displayed a
      partial protection against challenge infection. The purified rTsGST showed the
      maximum enzymatic activity at pH 6.5 and 40  degrees C. The enzymatic K m values
      for GSH and CDNB were 457 and 123 MUM, respectively. An in vitro invasion assay
      showed that when anti-rTsGST serum of mice infected with T. spiralis and normal
      mouse serum were added to the medium, and the invasion rate of the infective
      larvae in an intestinal epithelial cell (IEC) monolayer was 31.0, 11.36, and
      78.96%, respectively (P < 0.05), which indicates that anti-rTsGST antibodies
      partially inhibited the larval invasion of IEC. ADCC assay showed that anti
      rTsGST serum induced significant death of larvae (70% cytotoxicity) compared to
      the larvae incubated with pre-immune serum (12% cytotoxicity, P < 0.001) and was
      dose dependent.

PMID- 25758590
TI  - Medial patellar ligament splitting in horses with upward fixation of the patella:
      A long-term follow-up.
AB  - REASONS FOR PERFORMING STUDY: Medial patellar ligament splitting (MPLS) has been
      shown to be a highly effective and minimally invasive treatment for upward
      fixation of the patella (UFP) in horses. However, long-term follow-up results of
      this procedure have not previously been reported. OBJECTIVES: To evaluate the
      long-term resolution of UFP following MPLS and provide information on
      complications and recurrence. STUDY DESIGN: Retrospective case series. METHODS:
      Data were collected from horses that underwent MPLS between 1999 and 2013. All
      cases had a confirmed diagnosis of UFP that had not responded to conservative
      therapy. Data were collected from medical records, including follow-up visits and
      through telephone conversations with the owner, trainer or referring
      veterinarian. RESULTS: A total of 85 horses were included. Fifty-eight horses
      (68%) had surgery under general anaesthesia in dorsal recumbency, while 27 horses
      (32%) underwent standing surgery and 97.6% had complete resolution of the UFP
      immediately after surgery or within the 2 week rehabilitation period. Two cases
      (2.4%) had only unilateral resolution after bilateral surgery, even after the
      procedure was repeated. The majority of cases (90.5%) were followed up at least 3
      and up to 14 years after surgery. No short- or long-term complications were
      reported. No recurrence of UFP was observed in the horses that resumed exercise
      after surgery. CONCLUSIONS: Medial patellar ligament splitting is a highly
      effective and minimally invasive surgical procedure to treat UFP when
      conservative treatment is unsuccessful. In addition, it allows for a very rapid
      return to sports activity. No short- or long-term complications were observed and
      no recurrence of this condition was noted.

PMID- 25758589
TI  - Evaluation of multi-neuroprotective effects of erythropoietin using cisplatin
      induced peripheral neurotoxicity model.
AB  - Cisplatin (CDDP) is severely neurotoxic anti-neoplastic drug that causes
      peripheral neuropathies with clinical signs known as chemotherapy-induced
      peripheral neurotoxicity. The ameliorating effects of erythropoeitin on cisplatin
      induced neuropathy, which seem to be mediated by enhancing the cell resistance to
      side effects of cisplatin rather than by influencing the formation or repair
      rates of cisplatin-induced cross-links in the nuclear DNA, had been previously
      reported. The main objective of our study is to investigate the roles of nitro
      oxidative stress, nuclear factor kappa B (NFkappaB) gene expressions and TNF
      levels on the previous reported erythropoietin anti-apoptotic neuroprotective
      effects during cisplatin induced neurotoxicity. The present study compared the
      effects of erythropoietin (50 MUg/kg/d thrice weekly) on cisplatin (2mg/kg/d i.p.
      twice weekly for 4 weeks) induced neurophysiologic changes and the associated
      changes in the inflammatory mediators (TNF alpha and NFKB), oxidative stress
      (malondialdehyde (MDA), superoxide dismutases (SOD) and glutathione) and gene
      expression of both neuronal nitric oxide synthase (nNOS) and inducible nitric
      oxide synthase (iNOS). In addition, sciatic nerve pro-apoptotic and anti
      apoptotic indicators (Bcl, Bax, Caspase 3) were measured. We found that
      concomitant administration of erythropoietin significantly reversed the cisplatin
      induced nitro-oxidative stress - with significant increases in sciatic nerve
      glutathione and superoxide dismutase antioxidant enzyme levels and a significant
      decrease in iNOS gene expression. We conclude that erythropoietin anti-apoptotic
      neuro-protective effects could partially contribute to observed antioxidant
      effects of erthropoietin.

PMID- 25758592
TI  - Patients and healthcare conferences: what does true involvement look like?

PMID- 25758591
TI  - Superpersistent currents and whispering gallery modes in relativistic quantum
      chaotic systems.
AB  - Persistent currents (PCs), one of the most intriguing manifestations of the
      Aharonov-Bohm (AB) effect, are known to vanish for Schrodinger particles in the
      presence of random scatterings, e.g., due to classical chaos. But would this
      still be the case for Dirac fermions? Addressing this question is of significant
      value due to the tremendous recent interest in two-dimensional Dirac materials.
      We investigate relativistic quantum AB rings threaded by a magnetic flux and find
      that PCs are extremely robust. Even for highly asymmetric rings that host fully
      developed classical chaos, the amplitudes of PCs are of the same order of
      magnitude as those for integrable rings, henceforth the term superpersistent
      currents (SPCs). A striking finding is that the SPCs can be attributed to a
      robust type of relativistic quantum states, i.e., Dirac whispering gallery modes
      (WGMs) that carry large angular momenta and travel along the boundaries. We
      propose an experimental scheme using topological insulators to observe and
      characterize Dirac WGMs and SPCs, and speculate that these features can
      potentially be the base for a new class of relativistic qubit systems. Our
      discovery of WGMs in relativistic quantum systems is remarkable because, although
      WGMs are common in photonic systems, they are relatively rare in electronic
      systems. 

PMID- 25758593
TI  - Management of retinoblastoma: opportunities and challenges.
AB  - Nano-delivery systems have significantly evolved over the last decade for the
      treatment of cancer by enabling site-specific delivery and improved
      bioavailability. The widely investigated nanoparticle systems are biodegradable
      polyesters, dendrimers, liposomes, mesoporous silica and gold nanoparticles.
      These particles when conjugated with different targeting motifs enhance the
      therapeutic efficiency of the drug molecules and biocompatibility. However, the
      application of such systems towards the treatment of retinoblastoma (RB), a
      rapidly spreading childhood eye cancer, still remains in its infancy.
      Nanoparticle-based systems that have been investigated for RB therapy have
      displayed improved drug delivery to the most restricted posterior segment of the
      eyes and have increased intra-vitreal half-life of the chemotherapy agents
      highlighting its potential in treatment of this form of cancer. This review
      focuses on the challenges involved in the treatment of RB and highlights the
      attempts made to develop nano-dimensional systems for the treatment of RB.

PMID- 25758594
TI  - Genome-Wide Association Study and Linkage Analysis of the Healthy Aging Index.
AB  - BACKGROUND: The Healthy Aging Index (HAI) is a tool for measuring the extent of
      health and disease across multiple systems. METHODS: We conducted a genome-wide
      association study and a genome-wide linkage analysis to map quantitative trait
      loci associated with the HAI and a modified HAI weighted for mortality risk in
      3,140 individuals selected for familial longevity from the Long Life Family
      Study. The genome-wide association study used the Long Life Family Study as the
      discovery cohort and individuals from the Cardiovascular Health Study and the
      Framingham Heart Study as replication cohorts. RESULTS: There were no genome-wide
      significant findings from the genome-wide association study; however, several
      single-nucleotide polymorphisms near ZNF704 on chromosome 8q21.13 were
      suggestively associated with the HAI in the Long Life Family Study (p < 10(-)
      (6)) and nominally replicated in the Cardiovascular Health Study and Framingham
      Heart Study. Linkage results revealed significant evidence (log-odds score =
      3.36) for a quantitative trait locus for mortality-optimized HAI in women on
      chromosome 9p24-p23. However, results of fine-mapping studies did not implicate
      any specific candidate genes within this region of interest. CONCLUSIONS: ZNF704
      may be a potential candidate gene for studies of the genetic underpinnings of
      longevity.

PMID- 25758595
TI  - Inhibition of allergen-dependent IgE activity by antibodies of the same
      specificity but different class.
AB  - IgG4 purified from patients undergoing specific allergen immunotherapy inhibits
      the activities of the serum IgE in in vitro assays and is thought to reduce the
      symptoms of the disease. However, it is not known whether this is related to an
      intrinsic property of this subclass or only the allergen specificity. We tested
      the hypothesis that allergen specificity is the critical determinant for this
      activity using a panel of antibodies with identical specificity but different
      subclasses. The different antibodies were all able to inhibit the activity of IgE
      to the same extent. We demonstrate that specificity is the dominant factor
      determining the ability of an antibody to block allergen-dependent IgE activity.

PMID- 25758596
TI  - Anthocyanin-rich black elderberry extract improves markers of HDL function and
      reduces aortic cholesterol in hyperlipidemic mice.
AB  - Serum high-density lipoprotein-cholesterol (HDL-C) is a risk factor considered to
      be protective of atherosclerosis. However, atherosclerosis is an inflammatory
      disease and contributes to impairment in high-density lipoprotein (HDL) function,
      including reductions in HDL-C, HDL antioxidant and anti-inflammatory activities.
      Anthocyanins are polyphenols that have demonstrated antioxidant and anti
      inflammatory properties. The objective of this study was to determine whether an
      anthocyanin-rich black elderberry extract (Sambucus nigra) (BEE) (13%
      anthocyanins) would protect against inflammation-related impairments in HDL
      function and atherosclerosis in apoE(-/-) mice, a mouse model of hyperlipidemia
      and HDL dysfunction. We fed an AIN-93M diet supplemented with 1.25% (w/w) BEE or
      control diet to 10 week old male apoE(-/-) mice for 6 weeks. The BEE fed to mice
      was rich in cyanidin 3-sambubioside (~ 9.8% w/w) and cyanidin 3-glucoside (~ 3.8%
      w/w). After 6 weeks, serum lipids did not differ significantly between groups,
      while aspartate transaminase (AST) and fasting glucose were reduced in BEE-fed
      mice. Hepatic and intestinal mRNA changes with BEE-feeding were consistent with
      an improvement in HDL function (Apoa1, Pon1, Saa1, Lcat, Clu) and a reduction in
      hepatic cholesterol levels (increased Ldlr and Hmgcr, reduced Cyp7a1). In BEE-fed
      mice, serum paraoxonase-1 (PON1) arylesterase activity was significantly higher.
      In addition, mice fed BEE had significantly lower serum chemokine (C-C motif)
      ligand 2 (CCL2) compared to control-fed mice. Notably, we observed significant
      reductions in total cholesterol content of the aorta of BEE-fed mice, indicating
      less atherosclerosis progression. This study suggests that black elderberry may
      have the potential to influence HDL dysfunction associated with chronic
      inflammation by impacting hepatic gene expression.

PMID- 25758597
TI  - Receptor-templated stapling of intrinsically disordered peptide ligands.
AB  - We report here a chemoselective peptide "stapling" method that can be performed
      on ligand-receptor complexes in situ. An appropriately structured macrocyclic bis
      oxime linkage is shown to improve the affinity of a peptide ligand for its native
      protein receptor. The presence of the receptor as a template to preorganize the
      ligand into its bioactive conformation is found to bias reaction outcomes,
      suggesting the potential application of the method for receptor-assisted
      selection of stapled peptides. 

PMID- 25758598
TI  - Tackling the urban health divide though enabling intersectoral action on
      malnutrition in Chile and Kenya.
AB  - As momentum grows for a sustainable urbanisation goal in the post-2015
      development agenda, this paper reports on an action research study that sought to
      tackle the urban health divide by enabling intersectoral action on social
      determinants at the local level. The study was located in the cities of Mombasa
      in Kenya and Valparaiso in Chile, and the impact of the intervention on child
      nutrition was evaluated using a controlled design. The findings showed that an
      action research process using the social educational process known as PLA could
      effectively build the capacity of multisectoral teams to take coordinated action
      which in turn built the capacity of communities to sustain them. The impact on
      child nutrition was inconclusive and needed to be interpreted within the context
      of economic collapse in the intervention area. Four factors were found to have
      been crucial for creating the enabling environment for effective intersectoral
      action (i) supportive government policy (ii) broad participation and capacity
      building (iii) involving policy makers as advisors and establishing the
      credibility of the research and (iii) strengthening community action. If lessons
      learned from this study can be adapted and applied in other contexts then they
      could have a significant economic and societal impact on health and nutrition
      equity in informal urban settlements.

PMID- 25758599
TI  - Trends in Causes of Adult Deaths among the Urban Poor: Evidence from Nairobi
      Urban Health and Demographic Surveillance System, 2003-2012.
AB  - What kills people around the world and how it varies from place to place and over
      time is critical in mapping the global burden of disease and therefore, a
      relevant public health question, especially in developing countries. While more
      than two thirds of deaths worldwide are in developing countries, little is known
      about the causes of death in these nations. In many instances, vital registration
      systems are nonexistent or at best rudimentary, and even when deaths are
      registered, data on the cause of death in particular local contexts, which is an
      important step toward improving context-specific public health, are lacking. In
      this paper, we examine the trends in the causes of death among the urban poor in
      two informal settlements in Nairobi by applying the InterVA-4 software to verbal
      autopsy data. We examine cause of death data from 2646 verbal autopsies of deaths
      that occurred in the Nairobi Urban Health and Demographic Surveillance System
      (NUHDSS) between 1 January 2003 and 31 December 2012 among residents aged 15
      years and above. The data is entered into the InterVA-4 computer program, which
      assigns cause of death using probabilistic modeling. The results are presented as
      annualized trends from 2003 to 2012 and disaggregated by gender and age. Over the
      10-year period, the three major causes of death are tuberculosis (TB), injuries,
      and HIV/AIDS, accounting for 26.9, 20.9, and 17.3% of all deaths, respectively.
      In 2003, HIV/AIDS was the highest cause of death followed by TB and then
      injuries. However, by 2012, TB and injuries had overtaken HIV/AIDS as the major
      causes of death. When this is examined by gender, HIV/AIDS was consistently
      higher for women than men across all the years generally by a ratio of 2 to 1. In
      terms of TB, it was more evenly distributed across the years for both males and
      females. We find that there is significant gender variation in deaths linked to
      injuries, with male deaths being higher than female deaths by a ratio of about 4
      to 1. We also find a fifteen percentage point increase in the incidences of male
      deaths due to injuries between 2003 and 2012. For women, the corresponding deaths
      due to injuries remain fairly stable throughout the period. We find
      cardiovascular diseases as a significant cause of death over the period, with
      overall mortality increasing steadily from 1.6% in 2003 to 8.1% in 2012, and
      peaking at 13.7% in 2005 and at 12.0% in 2009. These deaths were consistently
      higher among women. We identified substantial variations in causes of death by
      age, with TB, HIV/AIDS, and CVD deaths lowest among younger residents and
      increasing with age, while injury-related deaths are highest among the youngest
      adults 15-19 and steadily declined with age. Also, deaths related to neoplasms
      and respiratory tract infections (RTIs) were prominent among older adults 50
      years and above, especially since 2005. Emerging at this stage is evidence that
      HIV/AIDS, TB, injuries, and cardiovascular disease are linked to approximately
      73% of all adult deaths among the urban poor in Nairobi slums of Korogocho and
      Viwandani in the last 10 years. While mortality related to HIV/AIDS is generally
      declining, we see an increasing proportion of deaths due to TB, injuries, and
      cardiovascular diseases. In sum, substantial epidemiological transition is
      ongoing in this local context, with deaths linked to communicable diseases
      declining from 66% in 2003 to 53% in 2012, while deaths due to noncommunicable
      causes experienced a four-fold increase from 5% in 2003 to 21.3% in 2012,
      together with another two-fold increase in deaths due to external causes
      (injuries) from 11% in 2003 to 22% in 2012. It is important to also underscore
      the gender dimensions of the epidemiological transition clearly visible in the
      mix. Finally, the elevated levels of disadvantage of slum dwellers in our
      analysis relative to other population subgroups in Kenya continue to demonstrate
      appreciable deterioration of key urban health and social indicators, highlighting
      the need for a deliberate strategic focus on the health needs of the urban poor
      in policy and program efforts toward achieving international goals and national
      health and development targets.

PMID- 25758600
TI  - Analysis of prognostic significance of merkel cell polyomavirus in chronic
      lymphocytic leukemia.
AB  - BACKGROUND: Merkel cell polyomavirus (MCPyV), a ubiquitous DNA tumor virus, has
      been found to be associated with Merkel cell carcinoma and chronic lymphocytic
      leukemia (CLL). Previous studies have reported conflicting results on the
      frequency and potential pathogenetic role of MCPyV in CLL. The aim of this study
      was to evaluate MCPyV's association with CLL and its prognostic significance.
      PATIENTS AND METHODS: Between 2006 and 2013, DNA samples obtained from CLL
      patients (n = 119) before treatment were tested for MCPyV using quantitative real
      time polymerase chain reaction analysis and verified by gel electrophoresis. Only
      samples testing positive by both methods were considered valid. RESULTS: We found
      that 13 (11%) of 119 CLL cases were positive for MCPyV. Between the groups of
      MCPyV-positive and -negative patients, there was no significant difference in the
      sex, age, cytogenetics, presence of p53 defect, or immunoglobulin heavy chain
      (IGHV) mutational status. In the subset of MCPyV-negative patients, advanced Rai
      stage (III to IV) was found more frequently, and therapy was initiated more
      often. There was no difference in overall response rate, median progression-free
      survival, and overall survival between both groups. We did not observe any new
      positivity after treatment in initially MCPyV-negative patients. CONCLUSION: This
      study provides the first analysis of the prognostic role of MCPyV in CLL. MCPyV
      occurrence seems to be a relatively rare event during the course of CLL. MCPyV is
      also unlikely to influence the outcome of CLL patients.

PMID- 25758602
TI  - Survival benefit of TIPS versus serial paracentesis in patients with refractory
      ascites: a single institution case-control propensity score analysis.
AB  - AIM: To compare the impact of covered stent-graft transjugular intrahepatic
      portosystemic shunt (TIPS) versus serial paracentesis on survival of patients
      with medically refractory ascites. MATERIALS AND METHODS: In this retrospective
      study, cirrhotic patients who underwent covered stent-graft TIPS for refractory
      ascites from 2003-2013 were compared with similar patients who underwent serial
      paracentesis during 2009-2013. Demographic and liver disease data, Model for End
      Stage Liver Disease (MELD) scores, and survival outcomes were obtained from
      hospital electronic medical records and the social security death index. After
      propensity score weighting to match study group characteristics, survival
      outcomes were compared using Kaplan-Meier statistics with log-rank analysis.
      RESULTS: Seventy TIPS (70% men, mean age 55.7 years, mean MELD 15.1) and 80
      paracentesis (58% men, mean age 53.5 years, mean MELD 22.5) patients were
      compared. The TIPS haemodynamic success rate was 100% (mean portosystemic
      pressure gradient reduction 13 mmHg). Paracentesis patients underwent a mean of
      7.9 procedures. After propensity score weighting to balance group features, TIPS
      patients showed a trend toward enhanced survival compared with paracentesis
      patients (median survival 1037 versus 262 days, p = 0.074). TIPS conferred a
      significant increase or trend toward improved survival compared with paracentesis
      at 1 (66% versus 44%, p = 0.018), 2 (56% versus 38%, p = 0.057), and 3 year (49%
      versus 32%, p = 0.077) time points. Thirty and 90 day mortality rates were not
      statistically increased by TIPS. CONCLUSION: Covered stent-graft TIPS improves
      intermediate- to long-term survival without significantly increasing short-term
      mortality of ascites patients, and suggests a greater potential role for TIPS in
      properly selected ascitic patients when medical management fails.

PMID- 25758601
TI  - EVEREST study report 2: imaging and grading protocol, and baseline
      characteristics of a randomised controlled trial of polypoidal choroidal
      vasculopathy.
AB  - PURPOSE: To describe the imaging standards, grading protocol and baseline
      characteristics of polypoidal choroidal vasculopathy (PCV) from the EVEREST
      study. METHODS: In a prospective, multicentre study, confocal scanning laser
      ophthalmoscope indocyanine green angiography (ICGA) was performed using a
      standardised imaging protocol. All images were graded using standardised,
      calibrated equipment by fellowship-trained ophthalmologists at the Central
      Reading Center. RESULTS: Sixty-one patients with PCV were included in the study.
      ICGA characteristics included: nodular appearance stereoscopically (56 eyes,
      91.8%), hypofluorescent halo (42, 68.9%), abnormal vascular network (54, 88.5%)
      and pulsation of the polyps (4, 6.6%). Colour fundus photography revealed orange
      subretinal nodules (34, 55.7%) and massive submacular haemorrhage (8, 13.1%). The
      mean area of the PCV lesion was 3.11 mm(2) (range, 0.2-10.7 mm(2)). The vascular
      channels filled within 7.3-32.0 s (mean: 17.9 s) while the mean filling time for
      polyps was 21.9 s (range, 7.3-40.4 s). Patients with massive submacular
      haemorrhage were less likely to have abnormal vascular channels seen on ICGA
      (28.6% vs 83.3% for those without massive haemorrhage, p=0.001). CONCLUSIONS: The
      imaging and grading protocols and baseline characteristics of a multicentre,
      randomised controlled trial of PCV are described in detail, and may serve as
      reference for future randomised, controlled trials on PCV. CLINICAL TRIAL NUMBER:
      This work was supported by Novartis Pharma AG, Basel, Switzerland grant number
      NCT00674323 (clinicaltrials.gov).

PMID- 25758603
TI  - Seat belt syndrome.

PMID- 25758604
TI  - Impaired right ventricular hemodynamics indicate preclinical pulmonary
      hypertension in patients with metabolic syndrome.
AB  - BACKGROUND: Metabolic disease can lead to intrinsic pulmonary hypertension in
      experimental models. The contributions of metabolic syndrome (MetS) and obesity
      to pulmonary hypertension and right ventricular dysfunction in humans remain
      unclear. We investigated the association of MetS and obesity with right
      ventricular structure and function in patients without cardiovascular disease.
      METHODS AND RESULTS: A total of 156 patients with MetS (mean age 44 years, 71%
      women, mean body mass index 40 kg/m(2)), 45 similarly obese persons without MetS,
      and 45 nonobese controls underwent echocardiography, including pulsed wave
      Doppler measurement of pulmonary artery acceleration time (PAAT) and ejection
      time. Pulmonary artery systolic pressure was estimated from PAAT using validated
      equations. MetS was associated with lower tricuspid valve e' (right ventricular
      diastolic function parameter), shorter PAAT, shorter ejection time, and larger
      pulmonary artery diameter compared with controls (P<0.05 for all). Estimated
      pulmonary artery systolic pressure based on PAAT was 42+/-12 mm Hg in
      participants with MetS compared with 32+/-9 and 32+/-10 mm Hg in obese and
      nonobese controls (P for ANOVA <0.0001). After adjustment for age, sex,
      hypertension, diabetes, body mass index, and triglycerides, MetS remained
      associated with a 20-ms-shorter PAAT (beta=-20.4, SE=6.5, P=0.002 versus obese).
      This association persisted after accounting for left ventricular structure and
      function and after exclusion of participants with obstructive sleep apnea.
      CONCLUSIONS: MetS is associated with abnormal right ventricular and pulmonary
      artery hemodynamics, as shown by shorter PAAT and subclinical right ventricular
      diastolic dysfunction. Estimated pulmonary artery systolic pressures are higher
      in MetS and preclinical metabolic heart disease and raise the possibility that
      pulmonary hypertension contributes to the pathophysiology of metabolic heart
      disease.

PMID- 25758606
TI  - Skeletal muscle oxidative capacity in patients with cystic fibrosis.
AB  - NEW FINDINGS: What is the central question of this study? Do patients with cystic
      fibrosis have reduced skeletal muscle oxidative capacity, measured with near
      infrared spectroscopy, compared with demographically matched control subjects?
      What is the main finding and is its importance? Patients with cystic fibrosis
      have impairments in skeletal muscle oxidative capacity. This reduced skeletal
      muscle oxidative capacity not only appears to be accelerated by age, but it may
      also contribute to exercise intolerance in patients with cystic fibrosis.
      Exercise intolerance predicts mortality in patients with cystic fibrosis (CF);
      however, the mechanisms have yet to be elucidated fully. Using near-infrared
      spectroscopy, in this study we compared skeletal muscle oxidative capacity in
      patients with CF versus healthy control subjects. Thirteen patients and 16
      demographically matched control subjects participated in this study. Near
      infrared spectroscopy was used to measure the recovery rate of oxygen consumption
      ( mus VO2max) of the vastus lateralis muscle after 15 s of electrical stimulation
      (4 Hz) and subsequent repeated transient arterial occlusions. The mus VO2max was
      reduced in patients with CF (1.82 +/- 0.4 min(-1) ) compared with control
      subjects (2.13 +/- 0.5 min(-1) , P = 0.04). A significant inverse relationship
      between age and mus VO2max was observed in patients with CF (r = -0.676, P =
      0.011) but not in control subjects (r = -0.291, P = 0.274). Patients with CF
      exhibit a reduction in skeletal muscle oxidative capacity compared with control
      subjects. It appears that the reduced skeletal muscle oxidative capacity is
      accelerated by age and could probably contribute to exercise intolerance in
      patients with CF.

PMID- 25758608
TI  - A Novel and Faster Method to Obtain a Differentiated 3-Dimensional Tissue
      Engineered Bladder.
AB  - PURPOSE: We report what is to our knowledge a novel approach that led to the
      rapid development of a 3-dimensional bladder model, including a differentiated
      urothelium reconstructed without a period of exposure to the air-liquid
      interface. MATERIALS AND METHODS: Bilayered bladder constructs were produced
      using anchored mesenchymal cell seeded collagen gels to create the mesenchymal
      layer. Gels were coated with urine for 20 minutes before urothelial cell seeding.
      The 3-dimensional bladder models were cultured under submerged conditions for 15
      days. RESULTS: Pure urine coating of the collagen matrix surface combined with
      its intermittent presence during urothelial development was found to be best to
      maintain urothelial cell properties. Immunohistological and ultrastructural
      analyses showed the formation of a pseudostratified urothelium devoid of abnormal
      K14 expression, allowing for uroplakin trafficking and forming an asymmetrical
      unit membrane at the apical surface. CONCLUSIONS: Such tissues could be adapted
      for clinical applications, including bladder repair. In the context of basic
      science this model could serve as a good alternative to animal use for
      fundamental and pharmacological studies of normal or pathological bladder
      tissues.

PMID- 25758607
TI  - Enhancing the efficacy of cytotoxic agents for cancer therapy using photochemical
      internalisation.
AB  - Photochemical internalisation (PCI) is a technique for improving cellular
      delivery of certain bioactive agents which are prone to sequestration within
      endolysosomes. There is a wide range of agents suitable for PCI-based delivery
      including toxins, oligonucleotides, genes and immunoconjugates which demonstrates
      the versatility of this technique. The basic mechanism of PCI involves triggering
      release of the agent from endolysosomes within the target cells using a
      photosensitiser which is selectively retained with the endolysosomal membranes.
      Excitation of the photosensitiser by visible light leads to disruption of the
      membranes via photooxidative damage thereby releasing the agent into the cytosol.
      This treatment enables the drugs to reach their intended subcellular target more
      efficiently and improves their efficacy. In this review we summarise the
      applications of this technique with the main emphasis placed on cancer
      chemotherapy.

PMID- 25758609
TI  - Comparison of Complications of Robot-Assisted Laparoscopic and Open
      Appendicovesicostomy in Children.
AB  - PURPOSE: Robot-assisted laparoscopic appendicovesicostomy in children has become
      increasingly popular. However, the literature on this technique mainly consists
      of small case series with only 1 small comparison to an open cohort. We compared
      the number of complications and surgical revisions required with open and robotic
      surgery in children undergoing appendicovesicostomy at our institution. MATERIALS
      AND METHODS: We retrospectively reviewed the charts of all patients who underwent
      appendicovesicostomy by 3 surgeons between July 2002 and September 2013. Acute
      complications and surgical revisions were recorded and compared between groups
      with t-tests for continuous variables and Fisher exact test for categorical
      variables. RESULTS: A total of 28 open and 39 robotic appendicovesicostomies were
      included. At a mean followup of 2.7 years there was no difference in number of
      complications or reoperations (p = 0.788 and p = 0.791, respectively) between
      groups. Time to first reoperation was shorter in the robotic group. However,
      there was no significant difference between groups regarding number of patients
      who underwent reoperation within the first 12 months postoperatively (p = 0.346).
      CONCLUSIONS: Comparison of robotic and open appendicovesicostomy revealed no
      significant difference in the number of acute complications or reoperations
      between groups. However, the nature and timing of complications differed between
      groups.

PMID- 25758610
TI  - Surgical Management of Local Retroperitoneal Recurrence of Renal Cell Carcinoma
      after Radical Nephrectomy.
AB  - PURPOSE: Isolated local retroperitoneal recurrence after radical nephrectomy for
      renal cell carcinoma poses a therapeutic challenge. We investigated outcomes in
      patients with localized retroperitoneal recurrence treated with surgical
      resection. MATERIALS AND METHODS: This was a retrospective, single institutional
      study of 102 patients with retroperitoneal recurrence treated with surgery from
      1990 to 2014. Demographics, clinical and pathological features, location of
      retroperitoneal recurrence and perioperative complications are reported using
      descriptive statistics. We studied recurrence-free and cancer specific survival
      using univariate and multivariate analyses. RESULTS: Median age at
      retroperitoneal recurrence diagnosis was 55 years (IQR 49-64). Cancer was pT3-4
      in 62 patients (60.8%) and pN1 in 20 (19.6%). No patients had distant metastatic
      disease at retroperitoneal recurrence surgery. Median time from nephrectomy to
      retroperitoneal recurrence diagnosis was 19 months (IQR 5-38.8). The median size
      of the resected retroperitoneal recurrence was 4.5 cm (IQR 2.7-7). Median
      followup after recurrence surgery was 32 months (IQR 16-57). Metastatic
      progression was observed in 60 patients (58.8%) postoperatively. Neoadjuvant and
      salvage systemic therapy was administered in 46 (45.1%) and 48 patients (47.1%),
      respectively. On multivariate analysis pathological nodal stage at original
      nephrectomy and maximum diameter of retroperitoneal recurrence were identified as
      independent risk factors for cancer specific death. CONCLUSIONS:
      Clinicopathological factors at nephrectomy as well as retroperitoneal recurrence
      surgery are important prognosticators. Aggressive surgical resection offers
      potential cure in a substantial number of patients with retroperitoneal
      recurrence with acceptable complications and still has a dominant role in the
      management of isolated locally recurrent RCC.

PMID- 25758611
TI  - Intracerebral Gene Therapy Using AAVrh.10-hARSA Recombinant Vector to Treat
      Patients with Early-Onset Forms of Metachromatic Leukodystrophy: Preclinical
      Feasibility and Safety Assessments in Nonhuman Primates.
AB  - No treatment is available for early-onset forms of metachromatic leukodystrophy
      (MLD), a lysosomal storage disease caused by autosomal recessive defect in
      arylsulfatase A (ARSA) gene causing severe demyelination in central and
      peripheral nervous systems. We have developed a gene therapy approach, based on
      intracerebral administration of AAVrh.10-hARSA vector, coding for human ARSA
      enzyme. We have previously demonstrated potency of this approach in MLD mice
      lacking ARSA expression. We describe herein the preclinical efficacy, safety, and
      biodistribution profile of intracerebral administration of AAVrh.10-hARSA to
      nonhuman primates (NHPs). NHPs received either the dose planned for patients
      adjusted to the brain volume ratio between child and NHP (1*dose, 1.1*10(11)
      vg/hemisphere, unilateral or bilateral injection) or 5-fold this dose (5*dose,
      5.5*10(11) vg/hemisphere, bilateral injection). NHPs were subjected to clinical,
      biological, and brain imaging observations and were euthanized 7 or 90 days after
      injection. There was no toxicity based on clinical and biological parameters, nor
      treatment-related histological findings in peripheral organs. A neuroinflammatory
      process correlating with brain MRI T2 hypersignals was observed in the brain 90
      days after administration of the 5*dose, but was absent or minimal after
      administration of the 1*dose. Antibody response to AAVrh.10 and hARSA was
      detected, without correlation with brain lesions. After injection of the 1*dose,
      AAVrh.10-hARSA vector was detected in a large part of the injected hemisphere,
      while ARSA activity exceeded the normal endogenous activity level by 14-31%.
      Consistently with other reports, vector genome was detected in off-target organs
      such as liver, spleen, lymph nodes, or blood, but not in gonads. Importantly,
      AAVrh.10-hARSA vector was no longer detectable in urine at day 7. Our data
      demonstrate requisite safe and effective profile for intracerebral AAVrh.10-hARSA
      delivery in NHPs, supporting its clinical use in children affected with MLD. 

PMID- 25758613
TI  - Association between parity, pre-pregnancy body mass index and gestational weight
      gain.
AB  - OBJECTIVE: To analyze the relationship between parity, pre-pregnancy body mass
      index (BMI), and gestational weight gain (GWG). METHODS: This observational
      controlled study was conducted from November 2013 to April 2014, with postpartum
      women who started antenatal care up to 14 weeks and had full-term births. Data
      were collected from medical records and antenatal cards. Descriptive and
      bivariate analyses were performed. The significance level was 5%. RESULTS: Data
      were collected from 130 primiparous and 160 multiparous women. At the beginning
      of prenatal care, 54.62% of the primiparous were eutrophic, while the majority of
      multiparous were overweight or obese (62.51%). Multiparas are two times more
      likely to be obese at the beginning of their pregnancies, when compared to
      primiparas. The average pre-pregnancy weight and final pregnancy weight was
      significantly higher in multiparous, however, the mean GWG was higher among
      primiparous. CONCLUSION: We found an inverse correlation between parity and the
      total GWG, but initial BMI was significantly higher in multiparas. Nevertheless,
      monitoring of the GWG through actions that promote a healthier lifestyle is
      needed, regardless of parity and nutritional status, in order to prevent
      excessive GWG and postpartum weight retention and consequently inadequate pre
      pregnancy nutritional status in future pregnancies.

PMID- 25758614
TI  - Body image in breastfeeding women with depressive symptoms: a prospective study.
AB  - The purpose of this prospective study was to investigate the relationship between
      body image perception and breastfeeding in puerperae with postpartum depression
      symptoms. The participants (147 healthy puerperae) completed The Edinburgh
      Postnatal Depression Scale (EPDS) and the Body Uneasiness Test (BUT-A and BUT-B),
      investigating body image perception and specific worries about particular body
      parts or functions. One month after discharge, new mothers participated in
      telephone interview concerning postpartum lactation practices. The subset of
      puerperae with EPDS score >9 also participated in psychological EPDS and BUT 6
      month follow up. Mothers with EPDS score >9 (28/147, 19.04 %) had significantly
      higher scores on BUT-A Global Severity Index (0.69 +/- 0.64 versus 0.37 +/- 0.31,
      p < 0.0001) and on BUT-B Positive Symptom Distress Index (0.74 +/- 0.57 versus
      0.41 +/- 0.42, p < 0004). In addition, the mothers with symptoms of depression
      were more likely (1:2) to interrupt full breastfeeding in the first month
      postpartum. At the 6-month follow up, the subset of new mothers with depression
      symptoms maintained elevated BUT-A and BUT-B scores, while EPDS >9 persisted in
      one-third of these. In conclusion, mothers with symptoms of depression have
      longlasting negative body image perception, persistent depressive symptoms, and
      they interrupt early full breastfeeding. 

PMID- 25758612
TI  - Angiostatic treatment prior to chemo- or photodynamic therapy improves anti-tumor
      efficacy.
AB  - Tumor vasculature is known to be poorly organized leading to increased leakage of
      molecules to the extravascular space. This process can potentially increase
      interstitial fluid pressure impairing intra-tumoral blood flow and oxygen supply,
      and can affect drug uptake. Anti-angiogenic therapies are believed to reduce
      vascular permeability, potentially reducing interstitial fluid pressure and
      improving the extravasation of small molecule-based chemotherapeutics. Here we
      show that pretreatment of human ovarian carcinoma tumors with sub-optimal doses
      of the VEGFR targeting tyrosine kinase inhibitor axitinib, but not the EGFR
      targeting kinase inhibitor erlotinib, induces a transient period of increased
      tumor oxygenation. Doxorubicin administered within this window was found to enter
      the extravascular tumor space more rapidly compared to doxorubicin when applied
      alone or outside this time window. Treatment with the chemotherapeutics,
      doxorubicin and RAPTA-C, as well as applying photodynamic therapy during this
      period of elevated oxygenation led to enhanced tumor growth inhibition.
      Improvement of therapy was not observed when applied outside the window of
      increased oxygenation. Taken together, these findings further confirm the
      hypothesis of angiostasis-induced vascular normalization and also help to
      understand the interactions between anti-angiogenesis and other anti-cancer
      strategies. 

PMID- 25758615
TI  - Is there a difference in breast milk fatty acid composition of mothers of preterm
      and term infants?
AB  - OBJECTIVE: Arachidonic acid (ARA) (c20:4 w6) and docosahexanoic acid (DHA) (c22:6
      w3) are of major importance for neural maturation and retinal function in
      infancy. Requirements in preterm infants are increased due to accelerated growth
      and limited body stores. Data regarding human milk fatty acid composition after
      preterm and full-term delivery is inconsistent. This study compared fatty acid
      composition in breast milk from full-term and preterm infants. Findings were
      correlated with maternal dietary intake. METHODS: Human milk was obtained 4-5
      days after full-term delivery (20 infants) and 4-5, 10-11 and 14-15 days after
      preterm delivery (21 infants, of whom 6 were born before 30 weeks). For fatty
      acid analysis, lipids were extracted, transesterified and separated by gas liquid
      chromatography. RESULTS: Total fat content was similar in the two groups. FA
      composition including LCPUFA and specifically ARA & DHA were similar in full-term
      and preterm infants and in the sub-set born before 30 weeks. In preterm infants,
      postnatal age did not influence LCPUFA content. CONCLUSIONS: This study did not
      detect any effect of gestational age or postnatal age on milk LCPUFA content.
      Accordingly, the increased demand for LCPUFA and specifically DHA in preterm
      infants need to be met by other supplementation.

PMID- 25758617
TI  - Neurodevelopment in children with intrauterine growth restriction: adverse
      effects and interventions.
AB  - Intrauterine growth restriction (IUGR) is associated with higher rates of fetal,
      perinatal, and neonatal morbidity and mortality. The consequences of IUGR include
      short-term metabolic, hematological and thermal disturbances that lead to
      metabolic syndrome in children and adults. Additionally, IUGR severely affects
      short- and long-term fetal brain development and brain function (including motor,
      cognitive and executive function) and neurobehavior, especially neuropsychology.
      This review details the adverse effects of IUGR on fetal brain development and
      discusses intervention strategies.

PMID- 25758616
TI  - Umbilical cord prostaglandins in term and preterm parturition.
AB  - OBJECTIVE: Prostaglandins (PGs) are considered the universal mediators of
      parturition. Amniotic fluid PGE2 and PGF2alpha concentrations increase before the
      onset of spontaneous labor at term, as well as during labor. This study was
      conducted to determine if the concentrations of umbilical cord PGE2 and PGF2alpha
      change with advancing gestational age, spontaneous labor at term, and preterm
      labor (with and without funisitis). METHODS: Umbilical cord (UC) tissue samples
      were obtained from women (N = 158) with singleton pregnancies in the following
      groups: (1) term deliveries without labor (TNL; n = 20); (2) term deliveries with
      labor (TIL; n = 20); (3) spontaneous preterm deliveries (sPTD) with (n = 20) and
      without acute funisitis (n = 20); and (4) preeclampsia without labor (n = 78).
      The concentrations of PGs were determined in different locations of the UC. PGE2
      and PGF2alpha were measured by specific immunoassays. Non-parametric statistics
      were used for analysis. RESULTS: (1) In spontaneous preterm deliveries, the
      median UC PGE2 concentration was higher in cases with funisitis than in those
      without funisitis (233.7 pg/ug versus 87.4 pg/ug of total protein, p = 0.001);
      (2) the median UC PGE2 concentration in sPTD with funisitis was also higher than
      that obtained from samples who had undergone labor at term (233.7 pg/ug versus
      116.1 pg/ug of total protein, p = 0.03); (3) the UC PGE2 and PGF2alpha
      concentration increased as a function of advancing gestational age before 36
      weeks (PGE2: rho = 0.59, p < 0.001; PGF2alpha: rho = 0.39, p = 0.01), but not
      after 36 weeks (PGE2: rho = -0.1, p = 0.5; PGF2alpha: rho = -0.2, p = 0.2); (4)
      the median UC concentrations of PGE2 and PGF2alpha at term was similar in samples
      obtained from women with and without labor (PGE2: TNL 133.7 pg/ug versus TIL
      116.1 pg/ug of total protein, p = 0.9; PGF2alpha: TNL 8.4 pg/ug versus TIL 8.1
      pg/ug of total protein, p = 0.7); and (5) there was no correlation between UC PG
      concentration and gestational age at term pregnancy (PGE2: rho = 0.01, p = 0.9;
      PGF2alpha: rho = 0.07, p = 0.7). CONCLUSIONS: (1) PGE2 concentrations in the UC
      are higher in the presence of acute funisitis than in the absence of this lesion;
      (2) spontaneous labor at term was not associated with a change in the UC
      concentration of PGE2 and PGF2alpha; and (3) the UC concentrations of PGE2 and
      PGF2alpha increased as a function of gestational age. We propose that UC PGs act
      as inflammatory mediators generated in the context of fetal systemic
      inflammation.

PMID- 25758619
TI  - Optimising daytime deliveries when inducing labour using prostaglandin vaginal
      inserts.
AB  - OBJECTIVE: To determine induction start time(s) that would maximise daytime
      deliveries when using prostaglandin vaginal inserts. METHODS: Women enrolled into
      the Phase III trial, EXPEDITE (clinical trial registration: NCT01127581), had
      labour induced with either a misoprostol or dinoprostone vaginal insert (MVI or
      DVI). A secondary analysis was conducted to determine the optimal start times for
      induction by identifying the 12-h period with the highest proportion of
      deliveries by parity and treatment. RESULTS: Optimal start times for achieving
      daytime deliveries when using MVI appear to be 19:00 in nulliparae and 23:00 in
      multiparae. Applying these start times, the median time of onset of active labour
      would be approximately 08:30 for both parities and the median time of delivery
      would be the following day at approximately 16:30 for nulliparae and 12:00
      (midday) for multiparae. Optimal start times when using DVI appear to be 07:00
      for nulliparae and 23:00 for multiparae. Using these start times, the median time
      of onset of active labour would be the following day at approximately 04:00 and
      11:50, and the median time of delivery would be approximately 13:40 and 16:10,
      respectively. CONCLUSIONS: When optimising daytime deliveries, different times to
      initiate induction of labour may be appropriate depending on parity and the type
      of retrievable prostaglandin vaginal insert used.

PMID- 25758618
TI  - A rapid interleukin-6 bedside test for the identification of intra-amniotic
      inflammation in preterm labor with intact membranes.
AB  - OBJECTIVE: Preterm birth is associated with 5-18% of pregnancies and is the
      leading cause of neonatal morbidity and mortality. Amniotic fluid (AF)
      interleukin-6 (IL-6) is a key cytokine for the identification of intra-amniotic
      inflammation, and patients with an elevated AF IL-6 are at risk for impending
      preterm delivery. However, results of the conventional method of measurement
      (enzyme-linked immunosorbent assay; ELISA) are usually not available in time to
      inform care. The objective of this study was to determine whether a point of care
      (POC) test or lateral-flow-based immunoassay for measurement of AF IL-6
      concentrations can identify patients with intra-amniotic inflammation and/or
      infection and those destined to deliver spontaneously before term among women
      with preterm labor and intact membranes. METHODS: One-hundred thirty-six women
      with singleton pregnancies who presented with symptoms of preterm labor and
      underwent amniocentesis were included in this study. Amniocentesis was performed
      at the time of diagnosis of preterm labor. AF Gram stain and AF white blood cell
      counts were determined. Microbial invasion of the amniotic cavity (MIAC) was
      defined according to the results of AF culture (aerobic and anaerobic as well as
      genital mycoplasmas). AF IL-6 concentrations were determined by both lateral flow
      based immunoassay and ELISA. The primary outcome was intra-amniotic inflammation,
      defined as AF ELISA IL-6 >= 2600 pg/ml. RESULTS: (1) AF IL-6 concentrations
      determined by a POC test have high sensitivity (93%), specificity (91%) and a
      positive likelihood ratio of 10 for the identification of intra-amniotic
      inflammation by using a threshold of 745 pg/ml; (2) the POC test and ELISA for IL
      6 perform similarly in the identification of MIAC, acute inflammatory lesions of
      placenta and patients at risk of impending spontaneous preterm delivery.
      CONCLUSION: A POC AF IL-6 test can identify intra-amniotic inflammation in women
      who present with preterm labor and intact membranes and those who will
      subsequently deliver spontaneously before 34 weeks of gestation. Results can be
      available within 20 min - this has important clinical implications and opens
      avenues for early diagnosis as well as treatment of intra-amniotic
      inflammation/infection.

PMID- 25758621
TI  - Neonatal outcomes following elective caesarean delivery at term: a hospital-based
      cohort study.
AB  - OBJECTIVE: To assess neonatal outcomes following elective caesarean delivery (CD)
      at term (>=37 + 0 weeks gestation). METHODS: A retrospective cohort study was
      conducted in a single Irish maternity hospital. Elective CDs at term between
      August 2008 and July 2012 were reviewed. Outcome measures were admission to the
      neonatal intensive care unit (NICU), length of stay, respiratory complications,
      hypoglycaemia, jaundice, newborn sepsis and medical interventions. RESULTS: A
      total of 4242 women had an elective CD at term, accounting for approximately 15%
      of all term deliveries. Admission rate to the NICU at 37 weeks gestation was
      21.8% versus 10% at 39 weeks (p for trend <0.0001). Similar trends of decreasing
      risk with later gestational age were noted for the other outcomes. An increased
      odds of admission to the NICU at 37 weeks [adjusted odds ratio (OR) 2.48 (95% CI
      1.28, 4.79)] and at 38 weeks [OR 1.34, 95% CI 1.02, 1.77] compared to the
      reference of 39 weeks gestation was found. CONCLUSIONS: This study supports
      evidence that, with regard to neonatal outcome, 39 weeks gestational age is the
      optimal delivery time. Heightened awareness of the increased risk of neonatal
      morbidity, when delivery is performed electively before 39 weeks, is warranted
      among healthcare workers.

PMID- 25758622
TI  - Screening and management of maternal colonization with Streptococcus agalactiae:
      an Italian cohort study.
AB  - INTRODUCTION: Streptococcus agalactiae (Group B streptococcus [GBS]) is the most
      common cause of sepsis and meningitis in infants <3 months of age. Intrapartum
      antibiotic prophylaxis (IAP) is effective in preventing the transmission of GBS
      to newborns. The Centers for Disease Control and Prevention (CDC) guidelines
      suggest vaginal and rectal cultures to assess GBS colonization between 35 and 37
      weeks' gestation. METHODS: Between July and December 2013, we identified 535
      women admitted to the Obstetric and Gynecology Unit of Cardarelli Hospital
      (Campobasso, Italy) for delivery. We evaluated the indications for IAP, complete
      execution of IAP, and neonatal outcomes. RESULTS: Our sample included 468 women
      and 475 live births. Correct screening for GBS was executed in 241 cases (51.5%),
      the number of women colonized was 96 (30.2%), and 136 women had indications to
      receive IAP, but only 68 (50%) received adequate treatment. CONCLUSIONS: GBS
      colonization status should be determined by collecting both vaginal and rectal
      specimens at 35-37 weeks' gestation. Inadequate screening for GBS and incorrect
      IAP led to an increased incidence of early-onset disease in newborns. Local
      public health agencies should promote surveillance and educational programs to
      prevent neonatal GBS infections.

PMID- 25758623
TI  - To study the effect of Kangaroo Mother Care on pain response in preterm neonates
      and to determine the behavioral and physiological responses to painful stimuli in
      preterm neonates: a study from western Rajasthan.
AB  - AIMS: To study the effect of Kangaroo Mother Care (KMC) on pain response in
      preterm neonates and to determine the behavioral and physiological responses to
      painful stimuli in preterm neonates. MATERIALS AND METHODS: This was a single
      blind cross over study in which total 140 neonates were enrolled. Pain stimulus
      was given in the form of heel-lance before and after giving KMC and data were
      recorded. RESULTS: The effect of KMC on heart rate variability was statistically
      significant in preterm (30-34 wks) and very low birth weight (1.0-1.5 kg)
      neonates. The mean fall in SpO2 from base line was less in KMC group as compared
      to without KMC group at 60 s (1.63% versus 2.22%) and 120 s (0.45% versus 2.22%).
      The mean duration of cry was less in the KMC group (15.05 s) as compared to
      without KMC group (24.82 s) and the difference was statistically significant (p <
      0.05). The mean duration of cry was reduced by 36% in KMC group as compared to
      the without KMC group. The effect of KMC on pain scores (premature infant pain
      profile (PIPP)) were significantly lower after heel-lance in KMC at 60 s (p <
      0.01). CONCLUSION: KMC is a most physiological, non-pharmacological and easy
      intervention that involves parents: to manage procedural pain that can be
      implemented for physiological or behavioral stability in their premature infants.

PMID- 25758625
TI  - Modelling umbilical vein blood flow normograms at 14-40 weeks of gestation by
      quantile regression analysis.
AB  - OBJECTIVE: To construct reference limits for gestation of umbilical vein blood
      flow (UVBF) in normal singleton pregnancies between 14 and 40 weeks of gestation
      using quantile regression. METHODS: We ultrasonographycally examined 852 fetuses
      from low-risk pregnancies between 16 and 40 weeks of gestation in a prospective
      cross-sectional study. UV diameter and time-averaged maximum velocity (TAMXV)
      were measured in UV intra-abdominal portion by real time and Doppler
      ultrasonography. A semi-automatic measurement software was used to obtain UV
      diameter values. UVBF was then calculated from UV diameter and TAMXV measurements
      and expressed both as absolute value and as value normalized for fetal abdominal
      circumference (UVBF/AC). Individual centile values of the variables investigated
      were established by quantile regression in the gestational interval considered.
      In 50 cases UVBF was measured twice by the same investigator or by a second
      investigator and the intra- and inter-observer agreement were calculated.
      RESULTS: A significant increase in UV diameter, TAMXV, UVBF absolute value and
      UVBF/AC was evidenced in the gestational period considered. Growth charts were
      established based on these measurements. The intra- and inter-observer intraclass
      correlation coefficients resulted as 0.92 (0.87-0.96) and 0.89 (0.84-0.97),
      respectively, for UBVF. CONCLUSIONS: In this study we constructed UVBF charts
      using quantile regression in a large cohort of low-risk pregnancies. These charts
      offer the advantage of specific estimated regression parameters for each
      percentile, better defining the normal range of UVBF. This promises to be useful
      in the diagnosis and management of fetuses with abnormal fetal growth.

PMID- 25758620
TI  - A point of care test for interleukin-6 in amniotic fluid in preterm prelabor
      rupture of membranes: a step toward the early treatment of acute intra-amniotic
      inflammation/infection.
AB  - OBJECTIVE: Preterm prelabor rupture of membranes (preterm PROM) accounts for 30
      40% of spontaneous preterm deliveries and thus is a major contributor to
      perinatal morbidity and mortality. An amniotic fluid (AF) interleukin-6 (IL-6)
      concentration is a key cytokine for the identification of intra-amniotic
      inflammation, patients at risk of impending preterm delivery and adverse
      pregnancy complications. The conventional method to determine IL-6 concentrations
      in AF is an enzyme-linked immunosorbent assay (ELISA). However, this technique is
      not available in clinical settings, and the results may take several days. A
      lateral flow-based immunoassay, or point of care (POC) test, has been developed
      to address this issue. The objective of this study was to compare the performance
      of AF IL-6 determined by the POC test to that determined by ELISA for the
      identification of intra-amniotic inflammation in patients with preterm PROM.
      MATERIALS AND METHODS: This retrospective cohort study includes 56 women with
      singleton pregnancies who presented with preterm PROM. Amniocentesis was
      performed at the time of diagnosis, and AF was analyzed using cultivation
      techniques for aerobic and anaerobic bacteria as well as genital mycoplasmas. AF
      Gram stain and AF white blood cell counts were determined. AF IL-6 concentrations
      were measured using both lateral flow-based immunoassay and ELISA. The primary
      outcome was intra-amniotic inflammation defined as AF ELISA IL-6 >= 2600 pg/ml. A
      previously determined cut-off of 745 pg/ml was used to define a positive POC
      test. RESULTS: (1) The POC test for AF IL-6 concentrations had 97% sensitivity
      and 96% specificity for the identification of intra-amniotic inflammation, as
      defined using ELISA among patients with preterm PROM and (2) the diagnostic
      performance of the POC test for IL-6 was strongly correlated to that of an ELISA
      test for the identification of intra-amniotic inflammation and was equivalent for
      the identification of acute inflammatory placental lesions and microbial invasion
      of the amniotic cavity (MIAC). CONCLUSION: A POC AF IL-6 test can identify intra
      amniotic inflammation in patients with preterm PROM. Results can be available
      within 20 min - this makes it possible to implement interventions designed to
      treat intra-amniotic inflammation and improve pregnancy outcomes.

PMID- 25758624
TI  - A multi-center randomized trial of two different intravenous fluids during labor.
AB  - OBJECTIVE: To determine if the intrapartum use of a 5% glucose-containing
      intravenous solution decreases the chance of a cesarean delivery for women
      presenting in active labor. METHODS: This was a multi-center, prospective, single
      (patient) blind, randomized study design implemented at four obstetric residency
      programs in Pennsylvania. Singleton, term, consenting women presenting in active
      spontaneous labor with a cervical dilation of <6 cm were randomized to lactated
      Ringer's with or without 5% glucose (LR versus D5LR) as their maintenance
      intravenous fluid. The primary outcome was the cesarean birth rate. Secondary
      outcomes included labor characteristics, as well as maternal or neonatal
      complications. RESULTS: There were 309 women analyzed. Demographic variables and
      admitting cervical dilation were similar among study groups. There was no
      significant difference in the cesarean delivery rate for the D5LR group (23/153
      or 15.0%) versus the LR arm (18/156 or 11.5%), [RR (95% CI) of 1.32 (0.75, 2.35),
      p = 0.34]. There were no differences in augmentation rates or intrapartum
      complications. CONCLUSIONS: The use of intravenous fluid containing 5% dextrose
      does not lower the chance of cesarean delivery for women admitted in active
      labor.

PMID- 25758626
TI  - The state of Illinois obstetric hemorrhage project: pre-project and post-training
      examination scores.
AB  - OBJECTIVE: The Illinois Department of Public Health mandated that all clinicians
      who provide care to obstetric patients participate in the Illinois Obstetric
      Hemorrhage Project. The aim of the current report is to describe change in
      knowledge among providers engaged in the project, as assessed by pre- and post
      tests. METHODS: The project, implemented 2008 to 2010, included four components:
      a written 25-item multiple-choice examination (pre-test), a didactic lecture,
      skill stations (for teaching blood loss estimation), and a simulation drill and
      debriefing. Participants completed a post-test 6 months later. Pre- and post-test
      examination scores were compared. RESULTS: Data from 95 hospitals are included in
      this analysis (9456 paired test results). The proportion of participants who
      scored >=88% correct answers increased from 10.9% on the pre-test to 49.1% on the
      post-test (p < 0.0001). Registered nurses made greater improvements in test
      scores than anesthesia and obstetric providers (p < 0.0001). CONCLUSIONS: The
      Illinois Obstetric Hemorrhage Project was successful in improving knowledge of
      obstetric hemorrhage in a large number of providers with different expertise and
      experience levels. Further long-term study is essential to determine whether the
      skills acquired during the Project contribute to improved obstetric hemorrhage
      outcomes for the women of Illinois.

PMID- 25758628
TI  - Intravenous carbetocin shot is superior to oxytocin infusion for placental
      delivery in second trimester abortion: a pilot randomized controlled trial.
AB  - OBJECTIVE: To study the efficacy of 100 MUg intravenous shot of carbetocin
      compared to 20 IU oxytocin intravenous infusion to prevent placental retention in
      second trimester medical termination of pregnancy. METHODS: A double-blinded
      randomized controlled trial was conducted at Ain Shams University Maternity
      Hospital from 1 April 2013 to 30 November 2013. A total of 132 women between 14
      and 24 weeks gestation indicated for termination were randomized to receive
      either 20 IU oxytocin infusion (n = 66) or 100 MUg carbetocin shot (n = 66) after
      fetal expulsion. Patients were observed for time elapsed between fetal and
      placental expulsion, presence of placental retention and blood loss. RESULTS:
      Third stage was 33.4 +/- 20.4 min in oxytocin group & 23.1 +/- 16.8 min in
      carbetocin group (p = 0.002). Eight patients (12.1%) in oxytocin group had
      complete placental retention versus two patients (3.0%) in carbetocin group (p =
      0.05). Eight patients (13.8%) received oxytocin had remnants of placenta compared
      to four patients (6.2%) received carbetocin (p = 0.04). Sixteen patients (24.2%)
      received oxytocin and six patients (9%) received carbetocin needed surgical
      curettage (p = 0.04). Third stage blood loss was 87.2 +/- 33.7 ml in carbetocin
      and 206.9 +/- 35.2 ml in oxytocin groups (p = 0.001). CONCLUSION: Carbetocin is
      superior to oxytocin infusion for management of placental delivery in second
      trimester abortion.

PMID- 25758627
TI  - The effect of prenatal alcohol co-exposure on neonatal abstinence syndrome in
      infants born to mothers in opioid maintenance treatment.
AB  - OBJECTIVE: This study examined the effects of prenatal alcohol exposure (PAE) on
      the incidence and severity of neonatal abstinence syndrome (NAS). STUDY DESIGN:
      For this pilot study, 70 pregnant women on opioid maintenance therapy (OMT) were
      recruited from a perinatal substance abuse clinic. Subjects were categorized into
      three study groups based on the timing of alcohol use during pregnancy as
      assessed by repeated self-reported measures and a comprehensive panel of ethanol
      biomarkers. NAS outcomes included: duration of hospital stay, the need for
      pharmacological treatment of NAS, newborn age at the initiation of NAS treatment,
      duration of treatment and cumulative methadone dose administered. RESULTS: The
      study included a large proportion of ethnic minorities (81.4% Hispanic, 5.7%
      American Indian), women with less than a high school education (52.2%) and
      unplanned pregnancy (82.9%). In multivariate analysis, PAE was not associated
      with NAS outcomes; however, one newborn diagnosed with fetal alcohol syndrome
      (FAS) demonstrated much more severe NAS compared to other PAE infants.
      Interestingly, 3rd trimester PAE was associated with a higher prevalence of
      microcephaly (62.5%) compared to the PAE abstaining group (36.8%; p = 0.08).
      CONCLUSION: In this study, PAE was not associated with NAS severity; however,
      further examination in a larger study is needed.

PMID- 25758629
TI  - Success rate of terbutaline in inhibiting preterm labor for 48 h.
AB  - OBJECTIVE: To determine terbutaline success rate in postponing preterm labor for
      48 h and to identify factors associated with its efficacy, side effects, maternal
      and neonatal outcomes. METHODS: A retrospective study analyzing data from
      pregnant women suffering from preterm labor who had received terbutaline for
      inhibition of labor from January 2007 to December 2013. RESULTS: A total of 385
      cases were analyzed; there were 321 cases (83.4%) delivered >=48 h and 64 cases
      (16.6%) delivered before 48 h. The factors that affect the success rate of
      terbutaline administration in singleton pregnancy were cervical dilatation (ORs
      0.37; 95% CI 0.18-0.79) and cervical effacement (ORs 0.36; 95% CI 0.17-0.75). The
      most common side effect of terbutaline was tachycardia (95.1%), but there were no
      serious cardiovascular events and maternal death. Mean neonatal birth weight was
      2.294.3 +/- 638.4 g. Neonatal complications included respiratory distress
      syndrome (RDS) 16.2%, intraventricular hemorrhage (IVH) 1.4%, necrotizing
      enterocolitis (NEC) 0.7%, sepsis 5.3%, and neonatal death 0.9%. CONCLUSIONS: The
      success rate of terbutaline in treatment of preterm labor was high whereas side
      effects were tolerable. Neonatal outcome was good. The factors that significantly
      affect the success rate of terbutaline administration in singleton pregnancy were
      cervical dilatation and cervical effacement. Thus, terbutaline can be used safely
      for short-term treatment of preterm labor.

PMID- 25758630
TI  - TNF-R1 as a first trimester marker for prediction of pre-eclampsia.
AB  - OBJECTIVE: To examine whether the maternal serum concentration of the soluble
      receptor-1 of tumor necrosis factor-alpha (TNF-R1) at 11-13 + 6 weeks of
      gestation is a predictor of development of pre-eclampsia (PE). METHODS: This is a
      nested case-control study in which the concentration of TNF-R1 at 11 + 0 to 13 +
      6 weeks was measured in 426 pregnant women in the first trimester. TNF-R1 values
      were expressed as multiples of the median (MoM) adjusted for maternal factors.
      The distributions of log TNF-R1 MoM in the control group and hypertensive
      disorders (early-PE [ePE], late-PE [lPE] and gestational hypertension [GH])
      groups were compared. Logistic regression analysis was used to determine whether
      maternal factors, TNF-R1 or their combination make a significant contribution to
      the prediction of PE. Screening performance was determined by analysis of
      receiver-operating characteristics curves. RESULTS: Median concentration of TNF
      R1 (ng/ml) was higher in ePE (2.62 +/- 0.67), lPE (2.12 +/- 0.56) and GH (2.19 +/
      0.45) compared to controls (2.04 +/- 0.42), p = 0.001. Logistic regression
      analysis demonstrated that the addition of TNFR-1 to maternal factors did not
      make a significant contribution to the prediction of PE. CONCLUSIONS: The
      maternal serum TNF-R1 concentration at 11-13 + 6 weeks of gestation was increased
      in pregnancies which developed hypertensive disorders, however, the addition of
      TNFR-1 did not improve the detection rate of these conditions compared with
      maternal factors alone.

PMID- 25758631
TI  - Lactoferrin and neonatology - role in neonatal sepsis and necrotizing
      enterocolitis: present, past and future.
AB  - Neonatal sepsis and necrotizing enterocolitis (NEC) are two most important
      neonatal problems in nursery which constitute the bulk of neonatal mortality and
      morbidity. Inflammatory mediators secondary to sepsis and NEC increases
      morbidity, by affecting various system of body like lung, brain and eye, thus
      causing long term implications. Lactoferrin (LF) is a component of breast milk
      and multiple actions that includes antimicrobial, antiviral, anti-fungal and anti
      cancer and various other actions. Few studies have been completed and a number of
      them are in progress for evaluation of efficacy and safety of LF in the
      prevention of neonatal sepsis and NEC in field of neonatology. In future, LF
      prophylaxis and therapy may have a significant impact in improving clinical
      outcomes of vulnerable preterm neonates. This review analyse the role of
      lactoferrin in prevention of neonatal sepsis and NEC, with emphasis on mechanism
      of action, recent studies and current studies going on around the globe. 

PMID- 25758632
TI  - Does being born small-for-gestational-age affect cerebellar size in neonates?
AB  - OBJECTIVE: To investigate how cerebellar vermis height (CVH) and transverse
      cerebellar diameter (TCD) measurements are affected in SGA neonates. METHODS: A
      total of 176 [88 SGA and 88 appropriate for gestational age (AGA)] neonates
      between 26 and 42 weeks of gestation were included. Midsagittal plane through the
      anterior fontanel and coronal plane through the left mastoid fontanel were used
      to measure CVH and TCD, respectively. CVH and TCD values were considered normal
      when they were >= 10th percentile, according to nomograms of AGA neonates.
      RESULTS: Thirty-six asymmetric SGA neonates, 52 symmetric SGA neonates and their
      88 gestational age-matched AGA controls were studied. The percentages of neonates
      with normal CVH and TCD in the symmetric SGA sub-group were significantly lower
      than those in the AGA and asymmetric SGA sub-groups. The percentages with normal
      CVH and TCD in the asymmetric SGA sub-group were also found to be low when
      compared with the AGA sub-group. CONCLUSION: Growth and development of cerebellum
      may be less spared in SGA neonates. Further studies with larger series are needed
      in order to evaluate how being born SGA (symmetric and asymmetric) affects
      cerebellar size and also to see how these findings influence the neurocognitive
      outcomes of these infants at long-term follow-up.

PMID- 25758633
TI  - The effect of empowerment program on "perceived readiness for discharge" of
      mothers of premature infants.
AB  - OBJECTIVES: Poor readiness of mothers to take care of their premature infant at
      the time of hospital discharge is associated with potential adverse consequences.
      The aim of this study was to examine the effect of empowerment program on
      "perceived readiness for discharge" of mothers of premature infants at the time
      of discharge. METHODS: A quasi-experimental before-after study design with
      consecutive inclusion of all mother-child pairs was used to conduct the study.
      Eighty mothers and their premature infants (40 pairs of mother-infant in the
      experimental group and 40 pairs of mother-infant in the control group) were
      recruited in the study. The program to empower the parents was implemented as a 3
      stage training plan for the experimental group. "Parent discharge readiness"
      questionnaire was completed by mothers before intervention and at discharge time,
      and was evaluated by nurses at discharge time. The groups were compared in terms
      of readiness for discharge according to the scores given by mothers and nurses.
      RESULTS: At discharge time, there was a statistically significant difference
      between technical readiness of control and experimental groups according to
      mothers' self-report (p < 0.001) and nurse evaluation (p < 0.0001). Also, there
      was a statistically significant difference between emotional readiness of mothers
      in control and experimental groups according to mothers' self-report (p < 0.0001)
      and nurse evaluation (p = 0.003). CONCLUSION: The implementation of empowerment
      program is an effective strategy to promote the readiness of mothers of premature
      infants at discharge time.

PMID- 25758635
TI  - Cold hardiness of the broad mite Polyphagotarsonemus latus (Acari: Tarsonemidae).
AB  - The cold hardiness of the broad mite, Polyphagotarsonemus latus, a key pest in
      Rhododendron simsii hybrid production in northwestern Europe, was investigated in
      the laboratory. Survival of eggs, larvae and female adults and reproduction
      capacity of female P. latus were evaluated following cold exposure at 7  degrees
      C. Adult females were also exposed to temperatures of 2 and -3  degrees C.
      Further, the supercooling point and lower lethal times of adult females were
      determined. No eggs survived exposure to 7  degrees C for 17 or more days. Larval
      survival upon the cold treatment decreased from 53 to 13% when exposed to 7 
      degrees C for 14 and 49 days, respectively. Two-day-old adult females exposed to
      7  degrees C for up to 42 days did not suffer significant mortality, but when
      returned to 25  degrees C their oviposition rates were lower than those of mites
      maintained at 25  degrees C. Less than 40% of females exposed for 13 days to 2 
      degrees C survived; only 20% of these females was able to reproduce upon
      recovery. Subzero temperatures dramatically decreased survival and reproduction
      capacity of adult females. The supercooling point of female adults was -16.5 
      degrees C. Median lethal times averaged 61.2 h and 9.3 days at -3 and 2  degrees
      C, respectively. In conclusion, a long term exposure (up to 6 weeks) of R. simsii
      plants infested with P. latus to a temperature of 7  degrees C, which is required
      for breaking dormancy of the flowers, is not expected to have detrimental effects
      on the survival and reproductive performance of the female mites.

PMID- 25758634
TI  - Involvement of a citrus meiotic recombination TTC-repeat motif in the formation
      of gross deletions generated by ionizing radiation and MULE activation.
AB  - BACKGROUND: Transposable-element mediated chromosomal rearrangements require the
      involvement of two transposons and two double-strand breaks (DSB) located in
      close proximity. In radiobiology, DSB proximity is also a major factor
      contributing to rearrangements. However, the whole issue of DSB proximity remains
      virtually unexplored. RESULTS: Based on DNA sequencing analysis we show that the
      genomes of 2 derived mutations, Arrufatina (sport) and Nero (irradiation), share
      a similar 2 Mb deletion of chromosome 3. A 7 kb Mutator-like element found in
      Clemenules was present in Arrufatina in inverted orientation flanking the 5' end
      of the deletion. The Arrufatina Mule displayed "dissimilar" 9-bp target site
      duplications separated by 2 Mb. Fine-scale single nucleotide variant analyses of
      the deleted fragments identified a TTC-repeat sequence motif located in the
      center of the deletion responsible of a meiotic crossover detected in the citrus
      reference genome. CONCLUSIONS: Taken together, this information is compatible
      with the proposal that in both mutants, the TTC-repeat motif formed a triplex DNA
      structure generating a loop that brought in close proximity the originally
      distinct reactive ends. In Arrufatina, the loop brought the Mule ends nearby the
      2 distinct insertion target sites and the inverted insertion of the transposable
      element between these target sites provoked the release of the in-between
      fragment. This proposal requires the involvement of a unique transposon and sheds
      light on the unresolved question of how two distinct sites become located in
      close proximity. These observations confer a crucial role to the TTC-repeats in
      fundamental plant processes as meiotic recombination and chromosomal
      rearrangements.

PMID- 25758636
TI  - Assessment of pain in critically ill children. Is cutaneous conductance a
      reliable tool?
AB  - PURPOSE: The purpose of this study is to assess the usefulness and accuracy of
      skin conductance (SC) as a tool to evaluate the level of sedation and pain in
      pediatric critical patients during painful procedures and to compare it with
      hemodynamic variables, clinical scales, and bispectral index (BIS). MATERIALS AND
      METHODS: This is a prospective observational study in 61 critical children
      undergoing invasive procedures. Hemodynamic data (heart rate and arterial blood
      pressure), clinical scales punctuation (Ramsay, COMFORT, and numeric rating pain
      scales), BIS, and the number of fluctuations of SC per second were collected
      before, during, and at the end of the procedure. RESULTS: The mean age of the
      patients was 42.9 (range, 1 month to 16 years). Seventy-two point six percent
      were postcardiac surgery patients. Nonmuscle-relaxed patients showed a moderate
      increase in heart rate (P = .02), numeric rating pain scales (P = .03), and
      Ramsay scale (P = .002). The number of fluctuations of SC per second increased
      significantly during the procedure (basal, 0.1; maneuver, 0.2; P = .015), but it
      never reached the level considered as pain or stress nor did it precede clinical
      scales or BIS. None of the variables studied showed a significant change during
      the procedure in muscle-relaxed patients. CONCLUSIONS: Skin conductance was not
      found to be more sensitive or faster than clinical scales for the assessment of
      pain or stress in critical children undergoing painful procedures. Skin
      conductance was not useful in muscle-relaxed children.

PMID- 25758637
TI  - Structural insights into the cubic-hexagonal phase transition kinetics of
      monoolein modulated by sucrose solutions.
AB  - Using DSC (differential scanning calorimetry), we measure the kinetics of the
      cubic-HII phase transition of monoolein in bulk sucrose solutions. We find that
      the transition temperature is dramatically lowered, with each 1 mol kg(-1) of
      sucrose concentration dropping the transition by 20  degrees C. The kinetics of
      this transition also slow greatly with increasing sucrose concentration. For low
      sucrose concentrations, the kinetics are asymmetric, with the cooling (HII-cubic)
      transition taking twice as long as the heating (cubic-HII) transition. This
      asymmetry in transition times is reduced for higher sucrose concentrations. The
      cooling transition exhibits Avrami exponents in the range of 2 to 2.5 and the
      heating transition shows Avrami exponents ranging from 1 to 3. A classical Avrami
      interpretation would be that these processes occur via a one or two dimensional
      pathway with variable nucleation rates. A non-classical perspective would suggest
      that these exponents reflect the time dependence of pore formation (cooling) and
      destruction (heating). New density measurements of monoolein show that the
      currently accepted value is about 5% too low; this has substantial implications
      for electron density modeling. Structural calculations indicate that the head
      group area and lipid length in the cubic-HII transition shrink by about 12% and
      4% respectively; this reduction is practically the same as that seen in a lipid
      with a very different molecular structure (rac-di-12:0 beta-GlcDAG) that makes
      the same transition. Thermodynamic considerations suggest there is a hydration
      shell about one water molecule thick in front of the lipid head groups in both
      the cubic and HII phases.

PMID- 25758638
TI  - Preoperative management of antithrombotic medication in Mohs micrographic
      surgery.

PMID- 25758639
TI  - Optimal antiplatelet therapy in out-hospital cardiac arrest patients treated by
      primary percutaneous coronary intervention.

PMID- 25758640
TI  - Generation of Distal Airway Epithelium from Multipotent Human Foregut Stem Cells.
AB  - Collectively, lung diseases are one of the largest causes of premature death
      worldwide and represent a major focus in the field of regenerative medicine.
      Despite significant progress, only few stem cell platforms are currently
      available for cell-based therapy, disease modeling, and drug screening in the
      context of pulmonary disorders. Human foregut stem cells (hFSCs) represent an
      advantageous progenitor cell type that can be used to amplify large quantities of
      cells for regenerative medicine applications and can be derived from any human
      pluripotent stem cell line. Here, we further demonstrate the application of hFSCs
      by generating a near homogeneous population of early pulmonary endoderm cells
      coexpressing NKX2.1 and FOXP2. These progenitors are then able to form cells that
      are representative of distal airway epithelium that express NKX2.1, GATA6, and
      cystic fibrosis transmembrane conductance regulator (CFTR) and secrete SFTPC.
      This culture system can be applied to hFSCs carrying the CFTR mutation Deltaf508,
      enabling the development of an in vitro model for cystic fibrosis. This platform
      is compatible with drug screening and functional validations of small molecules,
      which can reverse the phenotype associated with CFTR mutation. This is the first
      demonstration that multipotent endoderm stem cells can differentiate not only
      into both liver and pancreatic cells but also into lung endoderm. Furthermore,
      our study establishes a new approach for the generation of functional lung cells
      that can be used for disease modeling as well as for drug screening and the study
      of lung development. 

PMID- 25758641
TI  - Diagnostic accuracy and effectiveness of automated electronic sepsis alert
      systems: A systematic review.
AB  - BACKGROUND: Although timely treatment of sepsis improves outcomes, delays in
      administering evidence-based therapies are common. PURPOSE: To determine whether
      automated real-time electronic sepsis alerts can: (1) accurately identify sepsis
      and (2) improve process measures and outcomes. DATA SOURCES: We systematically
      searched MEDLINE, Embase, The Cochrane Library, and Cumulative Index to Nursing
      and Allied Health Literature from database inception through June 27, 2014. STUDY
      SELECTION: Included studies that empirically evaluated 1 or both of the
      prespecified objectives. DATA EXTRACTION: Two independent reviewers extracted
      data and assessed the risk of bias. Diagnostic accuracy of sepsis identification
      was measured by sensitivity, specificity, positive predictive value (PPV),
      negative predictive value (NPV), and likelihood ratio (LR). Effectiveness was
      assessed by changes in sepsis care process measures and outcomes. DATA SYNTHESIS:
      Of 1293 citations, 8 studies met inclusion criteria, 5 for the identification of
      sepsis (n = 35,423) and 5 for the effectiveness of sepsis alerts (n = 6894).
      Though definition of sepsis alert thresholds varied, most included systemic
      inflammatory response syndrome criteria +/- evidence of shock. Diagnostic
      accuracy varied greatly, with PPV ranging from 20.5% to 53.8%, NPV 76.5% to
      99.7%, LR+ 1.2 to 145.8, and LR- 0.06 to 0.86. There was modest evidence for
      improvement in process measures (ie, antibiotic escalation), but only among
      patients in non-critical care settings; there were no corresponding improvements
      in mortality or length of stay. Minimal data were reported on potential harms due
      to false positive alerts. CONCLUSIONS: Automated sepsis alerts derived from
      electronic health data may improve care processes but tend to have poor PPV and
      do not improve mortality or length of stay.

PMID- 25758642
TI  - Gut microbiome development along the colorectal adenoma-carcinoma sequence.
AB  - Colorectal cancer, a commonly diagnosed cancer in the elderly, often develops
      slowly from benign polyps called adenoma. The gut microbiota is believed to be
      directly involved in colorectal carcinogenesis. The identity and functional
      capacity of the adenoma- or carcinoma-related gut microbe(s), however, have not
      been surveyed in a comprehensive manner. Here we perform a metagenome-wide
      association study (MGWAS) on stools from advanced adenoma and carcinoma patients
      and from healthy subjects, revealing microbial genes, strains and functions
      enriched in each group. An analysis of potential risk factors indicates that high
      intake of red meat relative to fruits and vegetables appears to associate with
      outgrowth of bacteria that might contribute to a more hostile gut environment.
      These findings suggest that faecal microbiome-based strategies may be useful for
      early diagnosis and treatment of colorectal adenoma or carcinoma. 

PMID- 25758643
TI  - History of the pineal gland.

PMID- 25758644
TI  - Skull fracture mimicking eosinophilic granuloma.
AB  - BACKGROUND: Delayed swelling after skull fractures is an uncommon complication
      following head trauma in children. Classically, growing skull fractures typically
      present in patients under 3 years of age with progressive subcutaneous fluid
      collections, or occasionally with neurologic symptoms. We present the case of a
      healthy 2-year-old boy with a lytic "punched-out" frontal skull lesion. The child
      presented 2 months after a minor forehead injury for which no medical attention
      was sought. METHODS: The skull defect had no associated leptomeningeal cyst or
      brain herniation. Imaging and presentation were thought to be consistent with
      eosinophilic granuloma. Histologic findings demonstrated a healing skull
      fracture. RESULTS: Cranioplasty was performed, and the patient had an
      uncomplicated postoperative course. CONCLUSIONS: In this report, we describe our
      experience with this atypical presentation of a healing skull fracture mimicking
      a typical eosinophilic granuloma.

PMID- 25758645
TI  - Foraminiferal assemblages as bioindicators to assess potential pollution in
      mangroves used as a natural biofilter for shrimp farm effluents (New Caledonia).
AB  - In New Caledonia, semi-intensive shrimp farms release untreated effluents into
      the mangrove. Foraminiferal assemblages were analyzed for assessing the impact of
      effluent release on the benthic compartment. Comparison was made between samples
      collected (1) in an effluent receiving mangrove before and after the rearing
      cycle, and (2) for one-year monitoring an effluent receiving and a control
      mangrove. The distribution of foraminiferal assemblages was primarily driven by
      the gradient between Rhizophora stands and salt-flats, related to salinity and
      tidal elevation, and by seasonal cycles. The potential impact of effluent release
      was due to the combined effects of normal-saline effluents on surface salinity,
      and of nutrient input and microbial stimulation on food availability.
      Foraminiferal assemblages did not indicate a substantial impact of farm effluents
      and suggest that semi-intensive shrimp farming using mangrove for effluent
      discharge may appear as a sustainable solution in New Caledonia, when considering
      only the impact on the mangrove itself. 

PMID- 25758646
TI  - More than 95% completeness of reported procedures in the population-based Dutch
      Arthroplasty Register.
AB  - BACKGROUND AND PURPOSE: A complete and correct national arthroplasty register is
      indispensable for the quality of arthroplasty outcome studies. We evaluated the
      coverage, completeness, and validity of the Dutch Arthroplasty Register (LROI)
      for hip and knee arthroplasty. PATIENTS AND METHODS: The LROI is a nationwide
      population-based registry with information on joint arthroplasties in the
      Netherlands. Completeness of entered procedures was validated in 2 ways: (1) by
      comparison with the number of reimbursements for arthroplasty surgeries (Vektis
      database), and (2) by comparison with data from hospital information systems
      (HISs). The validity was examined by conducting checks on missing or incorrectly
      coded values in the LROI. RESULTS: The LROI contains over 300,000 hip and knee
      arthroplasties performed since 2007. Coverage of all Dutch hospitals (n = 100)
      was reached in 2012. Completeness of registered procedures was 98% for hip
      arthroplasty and 96% for knee arthroplasty in 2012, based on Vektis data. Based
      on comparison with data from the HIS, completeness of registered procedures was
      97% for primary total hip arthroplasty and 96% for primary knee arthroplasty in
      2013. Completeness of revision arthroplasty was 88% for hips and 90% for knees in
      2013. The proportion of missing or incorrectly coded values of variables was
      generally less than 0.5%, except for encrypted personal identity numbers (17% of
      which were missing) and ASA scores (10% of which were missing). INTERPRETATION:
      The LROI now contains over 300,000 hip and knee arthroplasty procedures, with
      coverage of all hospitals. It has a good level of completeness (i.e. more than
      95% for primary hip and knee arthroplasty procedures in 2012 and 2013) and the
      database has high validity.

PMID- 25758647
TI  - Correlation between serum levels of anti-endothelial cell autoantigen and anti
      dengue virus nonstructural protein 1 antibodies in dengue patients.
AB  - We have previously shown that anti-dengue virus nonstructural protein 1 (anti
      DENV NS1) antibodies cross-react with endothelial cells, and several autoantigens
      have been identified. This study shows that the antibody levels against these
      self-proteins are higher in sera from patients with dengue hemorrhagic fever
      (DHF) than those in control sera. Anti-protein disulfide isomerase (PDI) and anti
      heat shock protein 60 (anti-HSP60) IgM levels correlated with both anti
      endothelial cells and anti-DENV NS1 IgM titers. A cross-reactive epitope on the
      NS1 amino acid residues 311-330 (P311-330) had been predicted. We further found
      that there were higher IgM and IgG levels against P311-330 in DHF patients' sera
      than those in the control sera. In addition, correlations were observed between
      anti-PDI with anti-P311-330 IgM and IgG levels, respectively. Therefore, our
      results indicate that DENV NS1 P311-330 is a major epitope for cross-reactive
      antibodies to PDI on the endothelial cell surface, which may play an important
      role in DENV infection-induced autoimmunity.

PMID- 25758648
TI  - Etiology of pediatric fever in western Kenya: a case-control study of falciparum
      malaria, respiratory viruses, and streptococcal pharyngitis.
AB  - In Kenya, more than 10 million episodes of acute febrile illness are treated
      annually among children under 5 years. Most are clinically managed as malaria
      without parasitological confirmation. There is an unmet need to describe pathogen
      specific etiologies of fever. We enrolled 370 febrile children and 184 healthy
      controls. We report demographic and clinical characteristics of patients with
      Plasmodium falciparum, group A streptococcal (GAS) pharyngitis, and respiratory
      viruses (influenza A and B, respiratory syncytial virus [RSV], parainfluenza
      [PIV] types 1-3, adenovirus, human metapneumovirus [hMPV]), as well as those with
      undifferentiated fever. Of febrile children, 79.7% were treated for malaria.
      However, P. falciparum was detected infrequently in both cases and controls
      (14/268 [5.2%] versus 3/133 [2.3%], P = 0.165), whereas 41% (117/282) of febrile
      children had a respiratory viral infection, compared with 24.8% (29/117) of
      controls (P = 0.002). Only 9/515 (1.7%) children had streptococcal infection. Of
      febrile children, 22/269 (8.2%) were infected with > 1 pathogen, and 102/275
      (37.1%) had fevers of unknown etiology. Respiratory viruses were common in both
      groups, but only influenza or parainfluenza was more likely to be associated with
      symptomatic disease (attributable fraction [AF] 67.5% and 59%, respectively).
      Malaria was overdiagnosed and overtreated. Few children presented to the hospital
      with GAS pharyngitis. An enhanced understanding of carriage of common pathogens,
      improved diagnostic capacity, and better-informed clinical algorithms for febrile
      illness are needed.

PMID- 25758649
TI  - Microbial removals by a novel biofilter water treatment system.
AB  - Two point-of-use drinking water treatment systems designed using a carbon filter
      and foam material as a possible alternative to traditional biosand systems were
      evaluated for removal of bacteria, protozoa, and viruses. Two configurations were
      tested: the foam material was positioned vertically around the carbon filter in
      the sleeve unit or horizontally in the disk unit. The filtration systems were
      challenged with Cryptosporidium parvum, Raoultella terrigena, and bacteriophages
      P22 and MS2 before and after biofilm development to determine average log
      reduction (ALR) for each organism and the role of the biofilm. There was no
      significant difference in performance between the two designs, and both designs
      showed significant levels of removal (at least 4 log10 reduction in viruses, 6
      log10 for protozoa, and 8 log10 for bacteria). Removal levels meet or exceeded
      Environmental Protection Agency (EPA) standards for microbial purifiers.
      Exploratory test results suggested that mature biofilm formation contributed 1-2
      log10 reductions. Future work is recommended to determine field viability. 

PMID- 25758650
TI  - The impact of two semiannual treatments with albendazole alone on lymphatic
      filariasis and soil-transmitted helminth infections: a community-based study in
      the Republic of Congo.
AB  - Implementation of mass drug administration (MDA) with ivermectin plus albendazole
      (ALB) for lymphatic filariasis (LF) has been delayed in central Africa because of
      the risk of serious adverse events in subjects with high Loa loa microfilaremia.
      We conducted a community trial to assess the impact of semiannual MDA with ALB
      (400 mg) alone on LF and soil-transmitted helminth (STH) infections in the
      Republic of Congo. Evaluation at 12 months showed that ALB MDA had not
      significantly reduced Wuchereria bancrofti antigenemia or microfilaria (mf) rates
      in the community (from 17.3% to 16.6% and from 5.3% to 4.2%, respectively).
      However, the geometric mean mf count in mf-positive subjects was reduced from
      202.2 to 80.9 mf/mL (60% reduction, P = 0.01). The effect of ALB was impressive
      in 38 subjects who were mf-positive at baseline and retested at 12 months: 37%
      had total mf clearance, and individual mf densities were reduced by 73.0%. MDA
      also dramatically reduced the hookworm infection rate in the community from 6.5%
      to 0.6% (91% reduction), with less impressive effects on Ascaris and Trichuris.
      These preliminary results suggest that semiannual community MDA with ALB is a
      promising strategy for controlling LF and STH in areas with coendemic loiasis.

PMID- 25758651
TI  - Morbidity associated with schistosomiasis before and after treatment in young
      children in Rusinga Island, western Kenya.
AB  - Schistosoma mansoni infection is a major cause of organomegaly and ultimately
      liver fibrosis in adults. Morbidity in pre-school-aged children is less defined,
      and they are currently not included in mass drug administration (MDA) programs
      for schistosomiasis control. We report results of a study of the association of
      schistosomiasis with organomegaly in a convenience sample of 201 children under 7
      years old in Rusinga, Kenya on two cross-sectional visits, before and after
      praziquantel treatment. Data included stool examination and serology for
      schistosomiasis, the Niamey ultrasound protocol to stage hepatosplenic morbidity
      including organomegaly, and potential confounders including malaria. Unadjusted
      and adjusted Poisson regressions were performed. The baseline prevalence of
      schistosomiasis by antibody and/or stool was 80.3%. Schistomiasis was associated
      with hepatomegaly (adjusted prevalence ratio [aPR] = 1.4; 95% confidence interval
      [CI]: 1.0-2.1) and splenomegaly (aPR = 2.1; 95% CI: 1.2-3.7). The association
      with hepatomegaly persisted posttreatment (aPR = 1.4; 95% CI: 1.1-1.6).
      Schistosomiasis was associated with morbidity in this cohort. Efforts to include
      young children in mass treatment campaigns should intensify.

PMID- 25758652
TI  - The Effect of Storage and Extraction Methods on Amplification of Plasmodium
      falciparum DNA from Dried Blood Spots.
AB  - Extraction and amplification of DNA from dried blood spots (DBS) collected in
      field studies is commonly used for detection of Plasmodium falciparum. However,
      there have been few systematic efforts to determine the effects of storage and
      extraction methods on the sensitivity of DNA amplification. We investigated the
      effects of storage conditions, length of storage, and DNA extraction methods on
      amplification via three PCR-based assays using field samples and laboratory
      controls. Samples stored as DBS for 2 or more years at ambient temperature showed
      a significant loss of sensitivity that increased with time; after 10 years only
      10% samples with parasite densities > 1,000 parasites/MUL were detectable by
      nested polymerase chain reaction (PCR). Conversely, DBS and extracted DNA stored
      at -20 degrees C showed no loss of sensitivity with time. Samples with low
      parasite densities amplified more successfully with saponin/Chelex compared with
      spin-column-based extraction, though the latter method performed better on
      samples with higher parasite densities stored for 2 years at ambient temperature.
      DNA extracted via both methods was stable after 20 freeze-thaw cycles. Our
      results suggest that DBS should be stored at -20 degrees C or extracted
      immediately, especially if anticipating 2 or more years of storage.

PMID- 25758653
TI  - Trypanosoma cruzi Calreticulin Topographical Variations in Parasites Infecting
      Murine Macrophages.
AB  - Trypanosoma cruzi calreticulin (TcCRT), a 47-kDa chaperone, translocates from the
      endoplasmic reticulum to the area of flagellum emergence. There, it binds to
      complement components C1 and mannan-binding lectin (MBL), thus acting as a main
      virulence factor, and inhibits the classical and lectin pathways. The
      localization and functions of TcCRT, once the parasite is inside the host cell,
      are unknown. In parasites infecting murine macrophages, polyclonal anti-TcCRT
      antibodies detected TcCRT mainly in the parasite nucleus and kinetoplast.
      However, with a monoclonal antibody (E2G7), the resolution and specificity of the
      label markedly improved, and TcCRT was detected mainly in the parasite
      kinetoplast. Gold particles, bound to the respective antibodies, were used as
      probes in electron microscopy. This organelle may represent a stopover and
      accumulation site for TcCRT, previous its translocation to the area of flagellum
      emergence. Finally, early during T. cruzi infection and by unknown mechanisms, an
      important decrease in the number of MHC-I positive host cells was observed. 

PMID- 25758654
TI  - Age-Stratified Profiles of Serum IL-6, IL-10, and TNF-alpha Cytokines Among
      Kenyan Children with Schistosoma haematobium, Plasmodium falciparum, and Other
      Chronic Parasitic Co-Infections.
AB  - In a study of children having polyparasitic infections in a Schistosoma
      haematobium-endemic area, we examined the hypothesis that S. haematobium-positive
      children, compared with S. haematobium-negative children (anti-soluble worm
      antigen preparation [SWAP] negative and egg negative) have increased systemic
      production of pro-inflammatory cytokines (interleukin [IL]-6, tumor necrosis
      factor [TNF]-alpha) and decreased down-regulatory IL-10. A total of 804 children,
      2-19 years of age, were surveyed between July and December 2009 and tested for S.
      haematobium, Plasmodium falciparum, filariasis, and soil-transmitted helminth
      infections. Plasma levels of IL-6, TNF-alpha, and IL-10 were compared for S.
      haematobium-positive and S. haematobium-negative children, adjusting for malaria,
      filaria, and hookworm co-infections, and for nutritional status, age group, sex,
      and geographic location. IL-10 was significantly elevated among children infected
      with S. haematobium, showing bimodal peaks in 7-8 and 13-14 years age groups. IL
      10 was also higher among children who were acutely malnourished, whereas IL-10
      levels were lower in the presence of S. haematobium-filaria co-infection. After
      adjustment for co-factors, IL-6 was significantly elevated among children of 5-6
      years and among those with P. falciparum infection. Lower levels of IL-6 were
      found in malaria-hookworm co-infection. High levels of TNF-alpha were found in
      children aged 11-12 years regardless of infection status. In addition, village of
      residence was a strong predictor of IL-6 and IL-10 plasma levels. In adolescent
      children infected with S. haematobium, there is an associated elevation in
      circulating IL-10 that may reduce the risk of later morbidity. Although we did
      not find a direct link between S. haematobium infection and circulating pro
      inflammatory IL-6 and TNF-alpha levels, future T-cell stimulation studies may
      provide more conclusive linkages between infection and cytokine responses in
      settings that are endemic for multiple parasites and multiple co-infections.

PMID- 25758655
TI  - Experimental Hamster Infection with a Strain of Leptospira borgpetersenii Ballum
      Isolated from a Reservoir Mouse in New Caledonia.
AB  - Leptospirosis is a neglected zoonosis caused by pathogenic Leptospira. In this
      study, we characterized the virulence of isolate B3-13S obtained from a wild
      mouse (Mus musculus) captured in New Caledonia, subsequently identified as a
      bacterium belonging to the L. borgpetersenii serogroup Ballum. Hamsters were
      infected with an intraperitoneal injection of 2 * 10(8) bacteria, resulting in
      severe histopathological organ damages consistent with tissue lesions previously
      observed with other strains. Hamsters were also injected with 1 * 10(8) or 5 *
      10(7) bacteria and animals that recovered showed renal carriage of leptospires in
      concentrations similar to the bacterial load quantified in mouse kidneys, with
      urinary shedding of bacteria up to 4 weeks postinfection. The serogroup Ballum is
      increasingly reported in human leptospirosis, and these results highlight the use
      of the B3-13S isolate for the development of models resulting in either severe
      acute or chronic forms of the infection, allowing for better characterization of
      its pathogenesis. 

PMID- 25758656
TI  - Comment to 'Opdal AF, Jorgensen C (2015) Long-term change in a behavioural trait:
      truncated spawning distribution and demography in Northeast Arctic cod. Global
      Change Biology, 21:4, 1521-1530, doi: 10.1111/gcb.12773'.

PMID- 25758657
TI  - Patient-self assessment of flare in rheumatoid arthritis: translation and
      reliability of the Flare instrument.
AB  - The Flare instrument (FI) is a French self-administrated questionnaire used to
      identify flares in disease activity in patients with rheumatoid arthritis. In
      addition to a total score, the FI has two subscales: one relating to joint
      symptoms and one relating to general symptoms. The objective of this study was to
      translate and adapt the French FI into Danish and to determine the reliability of
      the FI in a consecutive cohort of patients with RA. The FI was translated
      according to international guidelines, tested among 10 patients and 5 health
      professionals, and adapted. Test-retest reliability was determined by the
      standard error of the measurement (SEM) and the intra class correlation
      coefficients (ICC). The FI was administered to 50 patients with rheumatoid
      arthritis from an outpatient clinic of a university hospital and re-administered
      after 10 days. The patients had a mean age of 65.3 years (SD 12.0) and mean
      disease duration of 18.1 years (range 2-47 years). We found an excellent
      reliability with ICC higher than 0.95 and SEM between 0.44 and 0.63. Best
      reliability was found in the total FI score. Thus, the results of the present
      study show that the FI is a feasible and reliable tool for evaluation of flares
      in patients with rheumatoid arthritis. 

PMID- 25758658
TI  - Electrochemotherapy, a potential new treatment for the management of squamous
      cell carcinoma in patients with recessive dystrophic epidermolysis bullosa:
      report of three cases.

PMID- 25758659
TI  - Investigating effects of atmospheric-pressure plasma on the process of wound
      healing.
AB  - Cold atmospheric-pressure plasma jets (APPJ) have excellent applications in
      biomedicine. Advantages of APPJ include lack of need for vacuum systems,
      capability of operation for a long time, and safe to be directly touched by
      living tissues such as a human body. In this study, an APPJ was generated by a
      dielectric barrier and applied for the treatment of chemical wounds. This APPJ
      worked with argon and was driven by high-voltage pulses. This paper compares the
      spontaneous healing of wounds and a stimulated healing using daily APPJ
      treatment. Biological data, such as hematological, biochemical, and histological
      parameters, were remarked. The mortality and morbidity of the untreated samples
      were reported after 20 days in comparison with the plasma-treated samples, which
      were alive after these days. Experimental results demonstrated that an increase
      in the oxidative stress could result in the decreased destruction of lesions by
      controlling the infection growth. These results were related to the presence of
      reactive oxygen species and reactive nitrogen species in the plasma volume, which
      were detected by optical emission spectroscopy. 

PMID- 25758660
TI  - ATG-induced accelerated immune senescence: clinical implications in renal
      transplant recipients.
AB  - Persistent ATG-induced CD4(+) T cell lymphopenia is associated with serious
      clinical complications. We tested the hypothesis that ATG induces accelerated
      immune senescence in renal transplant recipients (RTR). Immune senescence
      biomarkers were analyzed at transplant and one-year later in 97 incident RTR -62
      patients receiving ATG and 35 receiving anti-CD25 mAb (alpha-CD25). This
      consisted in: (i) thymic output; (ii) bone marrow renewal of CD34(+)
      hematopoietic progenitor cells (CD34(+) HPC) and lymphoid (l-HPC) and myeloid (m
      HPC) progenitor ratio; (iii) T cell phenotype; and (iv) measurement of T cell
      relative telomere length (RTL) and telomerase activity (RTA). Clinical correlates
      were analyzed with a 3 year follow-up. Thymic output significantly decreased one
      year posttransplant in ATG-treated patients. ATG was associated with a
      significant decrease in l-HPC/m-HPC ratio. Late stage differentiated CD57(+)
      /CD28(-) T cells increased in ATG-treated patients. One-year posttransplant T
      cell RTL and RTA were consequently lower in ATG-treated patients. ATG is
      associated with accelerated immune senescence. Increased frequency of late
      differentiated CD4(+) T cell frequency at transplantation tended to be predictive
      of a higher risk of subsequent opportunistic infections and of acute rejection
      only in ATG-treated patients but this needs confirmation. Considering
      pretransplant immune profile may help to select those patients who may benefit
      from ATG to prevent severe infections and acute rejection. 

PMID- 25758661
TI  - Exploitation of desilylation chemistry in tailor-made functionalization on
      diverse surfaces.
AB  - Interface engineering to attain a uniform and compact self-assembled monolayer at
      atomically flat surfaces plays a crucial role in the bottom-up fabrication of
      organic molecular devices. Here we report a promising and operationally simple
      approach for modification/functionalization not only at ultraflat single-crystal
      metal surfaces, M(111) (M=Au, Pt, Pd, Rh and Ir) but also at the highly oriented
      pyrolytic graphite surface, upon efficient in situ cleavage of trimethylsilyl end
      groups of the molecules. The obtained self-assembled monolayers are ultrastable
      within a wide potential window. The carbon-surface bonding on various substrates
      is confirmed by shell-isolated nanoparticle-enhanced Raman spectroscopy.
      Application of this strategy in tuning surface wettability is also demonstrated.
      The most valuable finding is that a combination of the desilylation with the
      click chemistry represents an efficient method for covalent and tailor-made
      functionalization of diverse surfaces. 

PMID- 25758663
TI  - [Effect of clopidogrel on plasma protein binding rate of ginsenosides: a liquid
      chromatography-mass spectrometry-based study].
AB  - OBJECTIVE: To investigate the effect of clopidogrel on the binding rate of
      ginsenosides with rat serum proteins (RSA). METHODS: Equilibrium dialysis and
      liquid chromatography-mass spectrometry were employed to quantify the
      concentration of ginsenoside Rg1 and Rb1. The protein-binding rates of Rg1 and
      Rb1 in the presence or absence of clopidogrel (1.0 mg/L) were determined. A
      molecular simulation model (consisting of homology modeling and molecular docking
      interaction) was used to reveal the target protein-compound interactions.
      RESULTS: The binding rates of ginsenosides Rg1 (0.4, 1.0, and 2.0 mg/L) with RSA
      were (30.16?2.82)%, (33.42?4.21)%, and (34.61?3.42)%, and those of and Rb1 were
      (50.13?2.34)%, (51.23?3.23)%, and (53.11?3.26)%, respectively. In the presence of
      clopidogrel, the binding rates of Rg1 decreased to (22.13?2.72)%, (21.42?3.22)%,
      and (25.45?3.52)%, and those of Rb1 to (40.13?3.24)%, (41.25?4.15)%, and
      (43.11?3.31)%, receptively. The molecular docking suggested that these compounds
      competed to bind with RSA. CONCLUSION: Clopidogrel can competitively bind to RSA
      with ginsenosides to lower the plasma protein binding rates of ginsenosides.

PMID- 25758664
TI  - Absence of family history and phenotype-genotype correlation in pediatric Brugada
      syndrome: more burden to bear in clinical and genetic diagnosis.
AB  - Brugada syndrome (BrS) is an autosomal-dominant genetic cardiac disorder caused
      in 18-30 % of the cases by SCN5A gene mutations and manifested by an atypical
      right bundle block pattern with ST segment elevation and T wave inversion in the
      right precordial leads. The syndrome is usually detected after puberty. The
      identification of BrS in pediatric patients is thus a rare occurrence, and most
      of the reported cases are unmasked after febrile episodes. Usually, having a
      family history of sudden death represents the first reason to perform an ECG in
      febrile children. However, this practice makes the sporadic cases of cardiac
      disease and specially the asymptomatic ones excluded from this diagnosis. Here,
      we report a sporadic case of a 2-month-old male patient presented with
      vaccination-related fever and ventricular tachycardia associated with short
      breathing, palpitation and cold sweating. ECG changes were consistent with type 1
      BrS. SCN5A gene analysis of the proband and his family revealed a set of
      mutations and polymorphisms differentially distributed among family members,
      however, without any clear genotype-phenotype correlation. Based on our findings,
      we think that genetic testing should be pursued as a routine practice in
      symptomatic and asymptomatic pediatric cases of BrS, with or without family
      history of sudden cardiac death. Similarly, our study suggests that pediatrician
      should be encouraged to perform an ECG profiling in suspicious febrile children
      and quickly manage fever since it is the most important factor unmasking BrS in
      children.

PMID- 25758662
TI  - Lysosomal targeting with stable and sensitive fluorescent probes (Superior
      LysoProbes): applications for lysosome labeling and tracking during apoptosis.
AB  - Intracellular pH plays an important role in the response to cancer invasion. We
      have designed and synthesized a series of new fluorescent probes (Superior
      LysoProbes) with the capacity to label acidic organelles and monitor lysosomal
      pH. Unlike commercially available fluorescent dyes, Superior LysoProbes are
      lysosome-specific and are highly stable. The use of Superior LysoProbes
      facilitates the direct visualization of the lysosomal response to lobaplatin
      elicited in human chloangiocarcinoma (CCA) RBE cells, using confocal laser
      scanning microscopy. Additionally, we have characterized the role of lysosomes in
      autophagy, the correlation between lysosome function and microtubule strength,
      and the alteration of lysosomal morphology during apoptosis. Our findings
      indicate that Superior LysoProbes offer numerous advantages over previous
      reagents to examine the intracellular activities of lysosomes. 

PMID- 25758665
TI  - Single-nucleotide polymorphisms and haplotypes of non-coding area in the CP gene
      are correlated with Parkinson's disease.
AB  - Our previous studies have demonstrated that ceruloplasmin (CP) dysmetabolism is
      correlated with Parkinson's disease (PD). However, the causes of decreased serum
      CP levels in PD patients remain to be clarified. This study aimed to explore the
      potential association between genetic variants of the CP gene and PD. Clinical
      features, serum CP levels, and the CP gene (both promoter and coding regions)
      were analyzed in 60 PD patients and 50 controls. A luciferase reporter system was
      used to investigate the function of promoter single-nucleotide polymorphisms
      (SNPs). High-density comparative genomic hybridization microarrays were also used
      to detect large-scale copy-number variations in CP and an additional 47 genes
      involved in PD and/or copper/iron metabolism. The frequencies of eight SNPs (one
      intronic SNP and seven promoter SNPs of the CP gene) and their haplotypes were
      significantly different between PD patients, especially those with lowered serum
      CP levels, and controls. However, the luciferase reporter system revealed no
      significant effect of the risk haplotype on promoter activity of the CP gene.
      Neither these SNPs nor their haplotypes were correlated with the Hoehn and Yahr
      staging of PD. The results of this study suggest that common genetic variants of
      CP are associated with PD and further investigation is needed to explore their
      functions in PD. 

PMID- 25758666
TI  - "Off-on" aggregation-based fluorescent sensor for the detection of chloride in
      water.
AB  - Receptors selective for anions in aqueous media are a crucial component in the
      detection of anions for biological and environmental applications. Recent sensor
      designs have taken advantage of systems known to aggregate in solution, eliciting
      a fluorescent response. Herein, we demonstrate a chloride-selective fluorescent
      response of receptor 1(+), based on our well-established class of 2,6-bis(2
      anilinoethynyl)pyridine bisureas. The fluorescence intensity ratio of 1(+).Cl(->)
      aggregates in water is four times larger than the next most fluorescent anion
      complex, 1(+).ClO4(->). In addition, (1)H NMR spectroscopic titrations
      demonstrate 1(+) binds chloride more strongly than other biologically relevant
      anions in solutions of both DMSO-d6 and 50/50 DMSO-d6/MeCN-d3. 

PMID- 25758667
TI  - Cryosurgery in association with itraconazole for the treatment of feline
      sporotrichosis.
AB  - OBJECTIVES: We evaluated the efficacy of cryosurgery in association with
      itraconazole for the treatment of feline sporotrichosis. We also compared the
      length of treatment protocol with others reported in the literature. METHODS:
      Cats naturally infected with fungi of the Sporothrix schenckii complex were
      evaluated. Diagnosis was confirmed by cytology and fungal culture. Prior to the
      cryosurgical procedure, every animal was receiving itraconazole 10 mg/kg/day PO,
      for different time periods. The same protocol was maintained until 4 weeks after
      complete healing of the lesions. RESULTS: Eleven of 13 cats were considered
      clinically cured. The treatment duration ranged from 14-64 weeks (median 32
      weeks). CONCLUSIONS AND RELEVANCE: The combination of cryosurgery and
      itraconazole was effective in treating cases of feline sporotrichosis and
      decreased the treatment length compared with protocols using only medication.

PMID- 25758668
TI  - Dinotefuran/pyriproxyfen/permethrin pemphigus-like drug reaction in three dogs.
AB  - BACKGROUND: Pemphigus foliaceus (PF) can occur spontaneously or as a reaction
      pattern associated with cutaneous adverse drug reactions. HYPOTHESIS/OBJECTIVES:
      To provide clinical, histological and immunological assessments of three dogs
      that developed cutaneous adverse drug reactions following application of a
      topical flea and tick control product, which contained dinotefuran, pyriproxyfen
      and permethrin. ANIMALS: Three client-owned dogs. RESULTS: The dogs exhibited
      rapid onset of papules, pustules and crusts at the site of application of the
      flea control product. In two dogs, the lesions became generalized, while the
      third exhibited a localized phenotype. Both dogs with generalized lesions
      required immunosuppressive treatment; one achieved remission after 1 year of
      treatment and one was euthanized due to adverse effects of glucocorticoids. The
      dog with a localized phenotype was treated with topical glucocorticoids
      exclusively and achieved remission after 10 months. Histology revealed subcorneal
      pustular dermatitis, with acantholysis of keratinocytes and focal to multifocal
      full-thickness epidermal necrosis. These features are similar to those previously
      reported for pesticide-triggered and spontaneous PF. Tissue-bound IgG was
      detected in two of three dogs, and autoantibodies targeting canine desmocollin-1
      were identified in the serum of the one dog from which a sample was available.
      CONCLUSIONS AND CLINICAL IMPORTANCE: Cutaneous adverse drug reaction caused by a
      flea control product containing dinotefuran, pyriproxyfen and permethrin closely
      resembled those reported for other pesticide-associated PF-like cutaneous adverse
      drug reactions. Although it appears to be a rare entity, clinicians and
      pathologists should be aware of the potential for flea and tick control products
      to trigger PF-like reactions.

PMID- 25758669
TI  - Five patient symptoms that you should evaluate every day.

PMID- 25758670
TI  - IP3 and calcium signaling involved in the reorganization of the actin
      cytoskeleton and cell rounding induced by cigarette smoke extract in human
      endothelial cells.
AB  - Smoking increases the risk of cardiovascular disorders and leads to damage caused
      by inflammation and oxidative stress. The actin cytoskeleton is a key player in
      the response to inflammatory stimuli and is an early target of cellular oxidative
      stress. The purpose of this study was to investigate the changes in actin
      cytoskeleton dynamics in human endothelial EA.hy926 cells exposed to cigarette
      smoke extract (CSE). Immunostaining revealed that CSE exposure resulted in
      modification of the actin cytoskeleton and led to cell rounding in a dose- and
      time-dependent manner. In addition, the intracellular calcium concentration was
      increased by treatment with CSE. Pretreatment with antioxidants (lipoic acid,
      glutathione, N-acetyl cysteine, aminoguanidine, alpha-tocopherol, and vitamin C)
      significantly attenuated the CSE-induced actin cytoskeleton reorganization and
      cell rounding. Calcium ion chelators (EGTA, BAPTA-AM AM) and a potent store
      operated calcium channel inhibitor (MRS 1845) also reduced CSE-induced
      intracellular calcium changes and attenuated actin cytoskeleton reorganization
      and cell morphology change. Moreover, the CSE-induced intracellular calcium
      increase was suppressed by pretreatment with the inositol trisphosphate receptor
      (IP3R) inhibitor xestospongin C, the phospholipase C (PLC) inhibitor U-73122, and
      the protein kinase C (PKC) inhibitor GF109203X. These results suggest that
      reactive oxygen species production and intracellular calcium increase play an
      essential role in CSE-induced actin disorganization and cell rounding through a
      PLC-IP3-PKC signaling pathway. (c) 2015 Wiley Periodicals, Inc. Environ Toxicol
      31: 1293-1306, 2016.

PMID- 25758672
TI  - Retraction of "Mechanical reconfiguration of stereoisomers".

PMID- 25758671
TI  - Chronic Childhood Peer Rejection is Associated with Heightened Neural Responses
      to Social Exclusion During Adolescence.
AB  - This functional Magnetic Resonance Imaging (fMRI) study examined subjective and
      neural responses to social exclusion in adolescents (age 12-15) who either had a
      stable accepted (n = 27; 14 males) or a chronic rejected (n = 19; 12 males)
      status among peers from age 6 to 12. Both groups of adolescents reported similar
      increases in distress after being excluded in a virtual ball-tossing game
      (Cyberball), but adolescents with a history of chronic peer rejection showed
      higher activity in brain regions previously linked to the detection of, and the
      distress caused by, social exclusion. Specifically, compared with stably accepted
      adolescents, chronically rejected adolescents displayed: 1) higher activity in
      the dorsal anterior cingulate cortex (dACC) during social exclusion and 2) higher
      activity in the dACC and anterior prefrontal cortex when they were incidentally
      excluded in a social interaction in which they were overall included. These
      findings demonstrate that chronic childhood peer rejection is associated with
      heightened neural responses to social exclusion during adolescence, which has
      implications for understanding the processes through which peer rejection may
      lead to adverse effects on mental health over time. 

PMID- 25758673
TI  - Retraction of "Mechanical activation of catalysts for C-C bond forming and
      anionic polymerization reactions from a single macromolecular reagent".

PMID- 25758674
TI  - Retraction of "Mechanically facilitated retro [4 + 2] cycloadditions".

PMID- 25758675
TI  - MRI phenotype of breast cancer: Kinetic assessment for molecular subtypes.
AB  - PURPOSE: To evaluate the dynamic contrast-enhanced magnetic resonance imaging
      (MRI) kinetic characteristics of newly diagnosed breast cancer molecular
      subtypes. MATERIALS AND METHODS: Breast MRI examinations of 112 patients with
      newly diagnosed breast cancer were reviewed. Cases of newly diagnosed invasive
      ductal carcinoma were sorted by molecular subtype (28 TN, 11 HER2 +, 73 Lum A/B)
      and MRI field strength, with lesion segmentation and kinetic analyses performed
      on a dedicated workstation. For kinetic assessment, 50% and 100% thresholds were
      employed for display of medium and rapid uptake. Kinetic profiles in terms of
      percent volume for six kinetic types (medium-persistent, medium-plateau, medium
      washout, fast-persistent, fast-plateau, fast-washout) relative to the whole
      volume of the lesion were obtained. Statistical analysis of the kinetic profiles
      was performed using Welch's t-test. RESULTS: Percent volume of HER2-positive
      lesions with >100% uptake at early phase on 3T strength MRI exams was
      significantly greater compared with luminal A/B (93.8 +/- 0.92 vs. 77.3 +/- 7.2;
      P < 0.01) and triple negative (93.8 +/- 0.92 vs. 81.3 +/- 8.2; P < 0.05)
      subtypes. The >50% early phase uptake for HER2+ lesions was also higher than Lum
      A/B (99.1 +/- 0.73 vs. 93.6 +/- 3.05; P < 0.01) at 3T. In the 1.5T subgroup the
      percent volume of HER2+ tumors with >50% and >100% early phase uptake trended
      higher than Lum A/B lesions without reaching significance. CONCLUSION: The
      percent volume of HER2-positive tumors demonstrating rapid early contrast uptake
      is significantly increased compared to other molecular subtypes.

PMID- 25758676
TI  - Physiological responses during downhill walking: A new exercise modality for
      subjects with chronic obstructive pulmonary disease?
AB  - Skeletal muscle quadriceps low-frequency fatigue (LFF) during exercise promotes
      improvements in exercise capacity with exercise training. In healthy subjects,
      eccentric muscle work induced by downhill walking (DW) generates higher muscular
      stress, whilst metabolic cost is lower compared to level walking (LW). We
      investigated quadriceps LFF and metabolic cost of DW in patients with chronic
      obstructive pulmonary disease. Ten participants (67 +/- 7 years, FEV1 51 +/- 15%
      predicted) performed DW, DW carrying a load (DWL) of 10% body weight via vest and
      LW, in random order. Quadriceps potentiated twitch force (TWqpot) was assessed
      before and after each walk, and muscle damage was assessed before and 24 hours
      after each walk via serum creatine kinase (CK) levels. Ventilation (VE) and
      oxygen consumption (VO2) were measured via breath-by-breath analysis during each
      walk. DW and DWL resulted in a greater decrease in TWqpot (-30 +/- 14 N in DW, p
      < 0.05; and -22 +/- 16 N in DWL, p < 0.05) compared to LW (-3 +/- 21 N, p >
      0.05). CK levels only increased 24 hours following DW and DWL (p < 0.05). DW and
      DWL showed lower VE and VO2 than LW (p < 0.05). DW is associated with enhanced
      quadriceps LFF and lower cardiorespiratory costs than LW. The addition of a chest
      load to DW does not seem to enhance these effects. 

PMID- 25758677
TI  - A systematic review of secondhand smoke exposure in a car: Attributable changes
      in atmospheric and biological markers.
AB  - Exposure to secondhand smoke (SHS) has been linked to disease, disability, and
      premature death. While several countries have enacted smoke-free legislations,
      exposure to SHS may still occur in unregulated private environments, such as in
      the family car. We performed a systematic review of peer-reviewed literature in
      PubMed and Web of Science up to May 2013. Articles were selected if they provided
      a quantitative measure of SHS exposure (biological or atmospheric markers); the
      study was conducted inside a car; and the assessed exposure was attributable to
      cigarette combustion. From 202 articles identified, 12 met the inclusion
      criteria. Among all studies that assessed smoking in cars with at least one
      window partially open, the particulate matter 2.5 MUm or less in diameter (PM2.5)
      concentrations ranged from 47 MUg/m(3) to 12,150 MUg/m(3). For studies with all
      windows closed, PM2.5 ranged from 203.6 MUg/m(3) to 13,150 MUg/m(3). SHS
      concentration in a car was mediated by air-conditioning status, extent of
      airflow, and driving speed. Smoking in cars leads to extremely high exposure to
      SHS and increased concentration of atmospheric markers of exposure-even in the
      presence of air-conditioning or increased airflow from open windows. This clearly
      shows that the only way to protect nonsmokers, especially children, from SHS
      within cars is by eliminating tobacco smoking. 

PMID- 25758678
TI  - Changes in plasma PPARs levels in migraine patients.
AB  - BACKGROUND: The aim of this study was to observe the change in plasma PPARs
      (peroxisome proliferator-activated receptors) level during various periods and in
      different subtypes in migraine patients. MATERIAL AND METHODS: We divided 227
      patients with migraine into 2 main groups: the attack period group (n=98) and the
      attack-free period group (n=129). Patients were further divided into 4 subgroups
      according to whether they had aura symptoms. The control group consisted of 100
      healthy subjects. We collected the clinical data of patients and measured the
      plasma levels of PPARs using enzyme-linked immunoassay (ELISA). We used SPSS
      software for statistical analysis. RESULTS: We found no significant difference in
      age, BMI, blood pressure, or blood lipid level among migraine patients during the
      headache attack period and during the headache-free period compared with the
      control group. The PPARalpha and PPARbeta/delta levels during the headache attack
      period were significantly higher than during the headache free period and in
      healthy controls. The PPARgamma levels during the headache attack period were
      significantly lower than those during the headache-free period and in the healthy
      control group. The PPARs levels during the headache attack period were
      significantly different from those during the headache-free period, regardless of
      presence or absence of aura. The PPARs levels during the headache-free period
      were not significantly different from those of the healthy control group. The
      level of PPARs has no significant differences between migraine with aura group
      and without aura group, regardless of whether headache attack. CONCLUSIONS: PPARs
      involved in the pathogenesis of migraine. Presence of absence of aura had no
      obvious effect on PPARs level.

PMID- 25758679
TI  - The world we live in.

PMID- 25758680
TI  - The global challenges of infectious diseases.

PMID- 25758681
TI  - Global inequality in kidney care.

PMID- 25758684
TI  - Implementing telehealth as core business in health services.

PMID- 25758685
TI  - Should we continue to isolate patients with vancomycin-resistant enterococci in
      hospitals?

PMID- 25758686
TI  - Stable post-TRUS biopsy sepsis rates and antibiotic resistance over 5 years in
      patients from Newcastle, New South Wales.

PMID- 25758687
TI  - Primary abdominal tuberculosis presenting as chronic dyspepsia.

PMID- 25758688
TI  - Latent infection in HIV-positive refugees and other immigrants in Australia.

PMID- 25758689
TI  - Compliance with Australian splenectomy guidelines in patients undergoing post
      traumatic splenectomy at a tertiary centre.

PMID- 25758690
TI  - Correction. Better prevention and management of heart failure in Aboriginal
      Australians.

PMID- 25758691
TI  - The G20, human health and sustainability: an interview with Jeffrey D Sachs.

PMID- 25758692
TI  - Facing the challenge of multidrug-resistant gram-negative bacilli in Australia.
AB  - Multidrug-resistant (MDR) gram-negative bacilli (GNB) are now globally widespread
      and present a major challenge to modern medical practice. Resistance to common
      antibiotics such as ceftriaxone is becoming more frequent in Australia, primarily
      mediated by extended-spectrum beta-lactamase enzymes in common organisms such as
      Escherichia coli, and may occur in both hospital- and community-acquired
      infections. Carbapenem-resistant Enterobacteriaceae have emerged rapidly in
      recent years and are well established in many countries in the Asia-Pacific
      region. Although rare at present in Australia, they have caused significant
      nosocomial outbreaks. GNB have numerous mechanisms by which they can develop
      antibiotic resistance. Genes that encode extended-spectrum beta-lactamases or
      carbapenemases are frequently co-located with multiple other resistance
      determinants on highly transmissible genetic structures such as plasmids. A key
      risk factor for infection with MDR GNB is travel to countries with high rates of
      resistance, especially with health care exposure. With limited prospects for new
      antibiotics in late-stage development that are active against MDR GNB, our
      national response to these challenges will require a multifaceted approach,
      including widespread implementation of antimicrobial stewardship, enhanced
      surveillance, targeted screening of at-risk patients and improved infection
      control practices. In the longer term, restriction of agricultural use of
      antibiotic classes critical to human medicine, removal of barriers to new drug
      development, and technological advances in rapid microbiological diagnostics will
      be required. 

PMID- 25758694
TI  - Effectiveness of a care bundle to reduce central line-associated bloodstream
      infections.
AB  - OBJECTIVE: To determine the effectiveness of a care bundle, with a novel line
      maintenance procedure, in reducing the rate of central line-associated
      bloodstream infection (CLABSI) in the intensive care unit (ICU). DESIGN,
      PARTICIPANTS AND SETTING: Before-and-after study using CLABSI data reported to
      the Victorian Healthcare Associated Infection Surveillance System (VICNISS), in
      adult patients admitted to a tertiary adult ICU in regional Victoria between 1
      July 2006 and 30 June 2014. VICNISS-reported CLABSI cases were reviewed for
      verification. An intervention was implemented in 2009. INTERVENTION: The care
      bundle introduced in 2009 included a previously established line insertion
      procedure and a novel line maintenance procedure comprising Biopatch, daily 2%
      chlorhexidine body wash, daily ICU central line review, and liaison nurse follow
      up of central lines. MAIN OUTCOME MEASURES: CLABSI rate (cases per 1000 central
      line days). RESULTS: The average CLABSI rate fell from 2.2/1000 central line days
      (peak of 5.2/1000 central line days in quarter 4, 2008) during the pre
      intervention period to 0.5/1000 central line days (0/1000 central line days from
      July 2012 to July 2014) during the post-intervention period. CONCLUSION: Our
      study suggests that this care bundle, using a novel maintenance procedure, can
      effectively reduce the CLABSI rate and maintain it at zero out to 2 years.

PMID- 25758695
TI  - The rise of targeted HIV oral rapid testing in Australia.
AB  - OBJECTIVE: To assess the performance and acceptability of the OraQuick Advance
      Rapid HIV-1/2 Antibody Test (ORT) in Australia. DESIGN, PARTICIPANTS AND SETTING:
      Cross-sectional study of 1074 men who have sex with men (MSM) and individuals
      aged 18 years or older at high risk of acquiring HIV infection who attended five
      public HIV or sexual health services, two general practices and one community
      clinic in Sydney from 1 January to 31 December 2013. INTERVENTION: One ORT
      confirmed by fourth-generation HIV enzyme immunoassay (EIA). MAIN OUTCOME
      MEASURES: ORT sensitivity and specificity compared with EIA; acceptabiity of the
      ORT to participants. RESULTS: 83.5% of participants were MSM, 90.3% were aged
      under 50 years, and 9% had never been tested for HIV. There were 11 true-positive
      ORT results, two false-negative (non-reactive) results (both were early
      infections), and one false-positive (reactive) result (due to reader error).
      Sensitivity and specificity were 84.6% and 99.8%, respectively (compared with a
      sensitivity of 99.3% and specificity of 99.8% listed by the manufacturer). Three
      quarters of participants (74.0%; 730/987) found the ORT less stressful than
      venous sampling. Those who usually had tests at intervals of greater than 3
      months deemed the ORT less stressful than those who had quarterly tests (77.5% v
      64.8%; P<0.001). Nearly all participants (99.2%; 998/1006) would have an ORT
      again and 99.4% (994/1000) would recommend it to peers. Most participants (69.1%;
      720/1042) felt ORT approval by Australia's Therapeutic Goods Administration (TGA)
      would encourage testing. CONCLUSION: ORT sensitivity is reduced in early HIV
      infection. The test is highly acceptable and less stressful than venous sampling.
      Participants are keen to be tested with the ORT in future, would recommend it to
      peers and would have tests more frequently if the ORT were licensed. TGA approval
      of this test might slow increasing HIV infection rates among MSM and others by
      facilitating diagnosis and treatment.

PMID- 25758696
TI  - HIV testing rates and co-infection among patients with tuberculosis in south
      eastern Sydney, 2008-2013.
AB  - OBJECTIVE: To evaluate the rate of HIV and tuberculosis co-infection and changes
      in HIV testing practices for patients with tuberculosis managed in South Eastern
      Sydney Local Health District (SESLHD), New South Wales, Australia. DESIGN,
      PARTICIPANTS AND SETTING: A retrospective review of tuberculosis notification
      data from four public tuberculosis treatment clinics in SESLHD (population,
      >800,000), 2008-2013. Data were extracted from the NSW Notifiable Conditions
      Information Management System. INTERVENTION: Published evidence regarding
      clinical management of HIV and tuberculosis co-infection and feedback of HIV
      testing rates was provided to senior clinicians managing tuberculosis in SESLHD
      between 2008 and 2012. MAIN OUTCOME MEASURES: Proportion of patients with
      tuberculosis with HIV infection status ascertained and proportion with HIV co
      infection. RESULTS: Of 506 people with notified tuberculosis treated in SESLHD
      during the study period, 369 had their HIV status ascertained (72.9%), of whom 20
      were HIV co-infected (5.4%). Eleven of these cases were new HIV diagnoses. Seven
      people offered an HIV test declined the offer. The rates of HIV co-infection
      varied between clinics (1.5%-9.7%; P=0.02) as did the rate of HIV status
      ascertainment (61.5%-85.4%; P<0.001). The rate of HIV status ascertainment
      increased between 2008 and 2013 (52.9%-87.1%; P<0.001). CONCLUSIONS: The rate of
      HIV co-infection among people treated for tuberculosis in south-eastern Sydney is
      of clinical importance. Rates of HIV testing in this population have increased,
      but further gains are desirable. It is unclear if the intervention influenced the
      increase in HIV testing rates.

PMID- 25758698
TI  - Respiratory tract infections among children younger than 5 years: current
      management in Australian general practice.
AB  - OBJECTIVE: To explore the current management in Australian general practice of
      common respiratory tract infections (RTIs) in children younger than 5 years.
      DESIGN, SETTING AND PARTICIPANTS: Analysis of data from a sample of 4522 general
      practitioners who participated in the Bettering the Evaluation and Care of Health
      (BEACH) cross-sectional survey, April 2007 to March 2012. Consultations with
      children younger than 5 years were analysed. MAIN OUTCOME MEASURES: GPs'
      management of four common RTIs (acute upper RTI [URTI], acute
      bronchitis/bronchiolitis, acute tonsillitis, and pneumonia) in association with
      six management options: antibiotic medications; prescribed or supplied non
      antibiotic medications; medications advised for over-the-counter purchase;
      referrals; pathology testing; and counselling. RESULTS: Of 31 295 encounters
      recorded, at least one of the four selected paediatric RTIs was managed at 8157
      encounters. URTI was managed 18.6 times per 100 GP patient encounters,
      bronchitis/bronchiolitis 4.2 times, acute tonsillitis 2.7 times, and pneumonia
      0.6 times per 100 encounters. Antibiotics were prescribed most frequently for
      tonsillitis and least frequently for URTI. Male GPs prescribed antibiotics for
      URTI significantly more often than female GPs, while older GPs prescribed
      antibiotics for URTI more often than younger GPs. CONCLUSION: GP management of
      paediatric RTIs in Australia varied according to the clinical problem and with
      age and sex of the GP. Further research into parents' and health professionals'
      attitudes and practices regarding the role of antibiotics, over-the-counter
      medications, and hygiene will help maintain favourable management practices.

PMID- 25758697
TI  - Evolving views and practices of antiretroviral treatment prescribers in
      Australia.
AB  - OBJECTIVE: To examine whether there have been recent changes in Australian
      antiretroviral treatment (ART) prescribers' perceptions and practices relating to
      early ART initiation, which was defined as commencing ART when a patient's CD4+ T
      cell count approaches 500 cells/mm3 or immediately after a patient is diagnosed
      with HIV. DESIGN, PARTICIPANTS AND SETTING: Self-completed, anonymous, cross
      sectional surveys, targeting all ART prescribers in Australia, were conducted
      online in 2012 and 2013. The surveys included questions on prescriber factors,
      CD4+ T-cell count at which prescribers would most strongly recommend ART
      initiation, and perceived patient characteristics that could change prescribers'
      practices of early initiation of ART. MAIN OUTCOME MEASURES: Proportions of ART
      prescribers recommending early ART initiation. RESULTS: We analysed responses
      from 108 participants in 2012 and 82 participants in 2013. In both years, more
      male than female prescribers participated. The median age of participants was 49
      years in 2012 and 50 years in 2013. In both rounds, over 60% had more than 10
      years' experience in treating HIV-positive patients. More prescribers in 2013
      stated that they would most strongly recommend early ART initiation compared with
      those in 2012 (50.0% [95% CI, 38.7%-61.3%] v 26.9% [95% CI, 18.8%-36.2%];
      P=0.001). The prescribers' primary concern was more about individual patient than
      public health benefit. Out of 824 patients for whom ART was initiated, as
      reported by prescribers in 2013, only 108 (13.1% [95% CI, 10.9%-15.6%]) were
      given ART primarily to prevent onward HIV transmission. The number of patients
      for whom ART was initiated was significantly associated with prescribers' HIV
      caseload even after adjusting for prescriber type (adjusted odds ratio, 1.73 [95%
      CI, 1.47-2.03]; P<0.001); of the 37 who had initiated ART for 10 or more
      patients, 29 had a high HIV caseload. In 2013, 60 prescribers (73.2% [95% CI,
      62.2%-82.4%]) reported that they routinely recommended ART to treatment-naive,
      asymptomatic patients with a CD4+ T-cell count of 350-500 cells/mm3. CONCLUSION:
      Our findings show increasing acceptance of and support for early ART initiation
      primarily as treatment and not as prevention.

PMID- 25758699
TI  - First reported case of transfusion-transmitted Ross River virus infection.

PMID- 25758700
TI  - Local acquisition and nosocomial transmission of Klebsiella pneumoniae harbouring
      the blaNDM-1 gene in Australia.

PMID- 25758701
TI  - Pyogenic brain abscess due to Streptococcus anginosus.

PMID- 25758702
TI  - Acute HIV infection presenting as erythema multiforme in a 45-year-old
      heterosexual man.

PMID- 25758703
TI  - Crystal structure of the C-terminal 2',5'-phosphodiesterase domain of group A
      rotavirus protein VP3.
AB  - In response to viral infections, the mammalian innate immune system induces the
      production of the second messenger 2'-5' oligoadenylate (2-5A) to activate latent
      ribonuclease L (RNase L) that restricts viral replication and promotes apoptosis.
      A subset of rotaviruses and coronaviruses encode 2',5'-phosphodiesterase enzymes
      that hydrolyze 2-5A, thereby inhibiting RNase L activation. We report the crystal
      structure of the 2',5'-phosphodiesterase domain of group A rotavirus protein VP3
      at 1.39 A resolution. The structure exhibits a 2H phosphoesterase fold and
      reveals conserved active site residues, providing insights into the mechanism of
      2-5A degradation in viral evasion of host innate immunity.

PMID- 25758704
TI  - Neurolymphomatosis: A report of 2 cases representing opposite ends of the
      clinical spectrum.
AB  - INTRODUCTION: Neurolymphomatosis (NL) is a rare disorder characterized by
      invasion of cranial or peripheral nerves, nerve roots, or plexi, usually by
      aggressive subtypes of non-Hodgkin lymphoma (NHL). The most common clinical
      presentation is that of a painful polyneuropathy or polyradiculopathy, followed
      by cranial neuropathy and, less frequently, by painless polyneuropathy. METHODS:
      Clinical and pathologic findings are reported for 2 NL cases. RESULTS: The
      following 2 patients with NL, with disparate clinical presentations, are
      presented: a patient with subacute onset, painful, multifocal, mixed axonal and
      demyelinating radiculoplexus neuropathy due to a large B-cell NHL, who required 2
      targeted fascicular nerve biopsies to demonstrate NL; and a patient with a slowly
      progressive, length-dependent axonal polyneuropathy due to a low-grade B-cell
      lymphoproliferative disorder, as shown on a diagnostic sural nerve biopsy.
      CONCLUSIONS: The cases described illustrate the wide clinical spectrum of NL.

PMID- 25758705
TI  - Having friends and feeling lonely: a daily process examination of transient
      loneliness, socialization, and drinking behavior.
AB  - Loneliness is a well-known indicator of relationship deficits, with potentially
      severe consequences on health and well-being (Perlman & Peplau, 1981). Research
      has used cross-sectional methods to examine behavioral consequences of loneliness
      (e.g., Cacioppo et al., 2002). However, within-person associations between daily
      fluctuations in loneliness and subsequent behavioral outcomes have yet to be
      explored. Using a sample of community-dwelling adults, the authors examined
      associations between daily loneliness on daily time with others, and subsequent
      context-specific alcohol consumption (i.e., social and solitary consumption), and
      individual differences in these patterns of behavior. Daytime loneliness
      significantly and uniquely predicted patterns of social behavior and context
      specific consumption; time with others mediated loneliness-social consumption
      associations, but not loneliness-solitary consumption relationships. These
      findings contribute to existing literature by demonstrating the unique properties
      of solitary versus social consumption as behavioral responses to loneliness, thus
      addressing inconsistent findings regarding the effects of loneliness on alcohol
      consumption. 

PMID- 25758706
TI  - Brutality under cover of ambiguity: activating, perpetuating, and deactivating
      covert retributivism.
AB  - Five studies tested four hypotheses on the drivers of punitive judgments. Study 1
      showed that people imposed covertly retributivist physical punishments on extreme
      norm violators when they could plausibly deny that is what they were doing
      (attributional ambiguity). Studies 2 and 3 showed that covert retributivism could
      be suppressed by subtle accountability manipulations that cue people to the
      possibility that they might be under scrutiny. Studies 4 and 5 showed how covert
      retributivism can become self-sustaining by biasing the lessons people learn from
      experience. Covert retributivists did not scale back punitiveness in response to
      feedback that the justice system makes false-conviction errors but they did ramp
      up punitiveness in response to feedback that the system makes false-acquittal
      errors. Taken together, the results underscore the paradoxical nature of covert
      retributivism: It is easily activated by plausible deniability and persistent in
      the face of false-conviction feedback but also easily deactivated by minimalist
      forms of accountability. 

PMID- 25758707
TI  - Counterfactuals, control, and causation: why knowledgeable people get blamed
      more.
AB  - Legal and prescriptive theories of blame generally propose that judgments about
      an actor's mental state (e.g., her knowledge or intent) should remain separate
      from judgments about whether the actor caused an outcome. Three experiments,
      however, show that, even in the absence of intent or immorality, actors who have
      knowledge relevant to a potential outcome will be rated more causal of that
      outcome than their ignorant counterparts, even when their actions were identical.
      Additional analysis revealed that this effect was mediated by counterfactual
      thinking--that is, by imagining ways the outcome could have been prevented.
      Specifically, when actors had knowledge, participants generated more
      counterfactuals about ways the outcome could have been different that the actor
      could control, which in turn increased causal assignment to the actor. These
      results are consistent with the Crediting Causality Model, but conflict with some
      legal and moral theories of blame.

PMID- 25758708
TI  - Magnetic Resonance Imaging of Temporal Arteritis: A Case Report.

PMID- 25758709
TI  - Overcoming inefficient secretion of recombinant VEGF-C in baculovirus expression
      vector system by simple purification of the protein from cell lysate.
AB  - The first reports about successfully expressed recombinant proteins with the use
      of a baculovirus vector were published over 30years ago. Despite the long time of
      refining this expression system, early problems with the production of
      baculovirus-derived secretory proteins are still not satisfactorily solved. The
      high expression level driven by baculoviral promoters often does not result in
      the desired yield of secreted recombinant proteins, which frequently accumulate
      inside insect cells and are only partially processed. During our attempts to
      produce vascular endothelial growth factor C (VEGF-C) with the use of a
      baculovirus vector we also faced an inefficient secretion of the recombinant
      protein to culture medium. We were not able to improve the outcome and obtain an
      acceptable concentration of VEGF-C in the medium by changing the culture
      conditions or utilizing different signal peptides. However, as a significant
      amount of native VEGF-C was detected inside the baculovirus-infected cells, we
      developed a simple method to purify recombinant, glycosylated VEGF-C from a
      lysate of the cells. The presented results indicate that the lack of a secretory
      protein in the insect cell culture medium after baculovirus infection does not
      necessarily signify failure in the production of the protein. As demonstrated by
      us and contrary to generally accepted views, the lysate of baculovirus-infected
      cells may constitute a valuable source of the biologically active, secretory
      protein. 

PMID- 25758710
TI  - Larger visual stimuli are perceived to last longer from time to time: The
      internal clock is not affected by nontemporal visual stimulus size.
AB  - Performance on interval timing is often explained by the assumption of an
      internal clock based on neural counting. According to this account, a neural
      pacemaker generates pulses, and the number of pulses relating to a physical time
      interval is recorded by a counter. Thus, the number of accumulated pulses is the
      internal representation of this interval. Several studies demonstrated that large
      visual stimuli are perceived to last longer than smaller ones presented for the
      same duration. The present study was designed to investigate whether nontemporal
      visual stimulus size directly affects the internal clock. For this purpose, a
      temporal reproduction task was applied. Sixty participants were randomly assigned
      to one of two experimental conditions with stimulus size being experimentally
      varied within either the target or the reproduction interval. A direct effect of
      nontemporal stimulus size on the pacemaker-counter system should become evident
      irrespective of whether stimulus size was experimentally varied within the target
      or the reproduction interval. An effect of nontemporal stimulus size on
      reproduced duration only occurred when stimulus size was varied during the target
      interval. This finding clearly argues against the notion that nontemporal visual
      stimulus size directly affects the internal clock. Furthermore, our findings
      ruled out a decisional bias as a possible cause of the observed differential
      effect of stimulus size on reproduced duration. Rather the effect of stimulus
      size appeared to originate from the memory stage of temporal information
      processing at which the timing signal from the pacemaker-counter component is
      encoded in reference memory. 

PMID- 25758711
TI  - The effects of shape crowding on grasping.
AB  - Crowding refers to the deleterious effect of nearby objects on the identification
      of a target in the peripheral visual field. A recent study (Chen, Sperandio, &
      Goodale, 2015) showed that when a three-dimensional (3D) disk was crowded by
      disks of different sizes, participants could scale their grip aperture to the
      size of the target, even when they could not perceive its size. It is still
      unclear, however, whether or not grasping can also escape to some degree the
      crowding of other object features, such as shape. To test this, we presented 3D
      rectangular blocks in isolation or crowded by other blocks in the periphery. The
      target and flanking blocks had the same surface area but different dimensions.
      Participants were required either to grasp the target block across its width or
      to estimate its width. We found that, consistent with what we observed earlier
      with size, participants can also scale their grasp to the width of the target
      block even when they could not perceive its width. To further explore whether or
      not the effect of crowding on grasping depends on how proficient people are with
      their right hand, we had right-handed participants perform the same test but with
      their left hand. We found that left-hand grasping did not escape the crowding
      effect on shape perception at all. Taken together, our results suggest that
      people can also use invisible shape information to guide actions and that this
      ability depends on the proficiency of the action. 

PMID- 25758713
TI  - Multiple effects of IL-21 on human NK cells in ex vivo expansion.
AB  - Natural killer (NK) cells (CD56(+)CD3(-)) are large, granular immunocytes that
      play a very pivotal role in the anti-inflammatory response and tumor
      surveillance. As an ideal cytotoxic lymphocyte (CTL), NK cells have attracted
      much attention in clinical trials. However, an insufficient number and their
      limited life span are bottlenecks that limit the application of NK cells in
      adoptive immunotherapy. Interleukins such as IL-2, IL-15 and IL-18 are recognized
      as factors that stimulate NK cells and have been used in NK cells ex vivo
      expansion. Similar to IL-2 and IL-15, IL-21 is a common gamma-chain cytokine that
      is important in NK cell activation, maturation and proliferation. The present
      study aims to assess the effects of membrane-bound and soluble IL-21 on primary
      human NK cells during ex vivo expansion. IL-21 was found to have multiple effects
      on NK cells, increasing their cytotoxicity in a concentration-dependent manner by
      up-regulating IFN-gamma and Granzyme-B expression. Nevertheless, at a high
      concentration (50 ng/mL), IL-21 curtailed the life span of NK cells by
      significantly inducing apoptosis. Moreover, when treated with IL-21, the number
      of NKT (CD56(+)CD3(+)) cells increased among peripheral blood mononuclear cells
      (PBMCs) during ex vivo expansion in a concentration-dependent manner. IL-21 also
      promoted expanded cells to enter into S phase of the cell cycle during the first
      to second weeks of culture. All these results suggest that IL-21 has multiple
      effects on NK cell development and functions. More attention should be given to
      the dosage and multiple effects of IL-21 when it was applied to NK cells in ex
      vivo expansion.

PMID- 25758714
TI  - Fasciola hepatica excretory-secretory products induce CD4+T cell anergy via
      selective up-regulation of PD-L2 expression on macrophages in a Dectin-1
      dependent way.
AB  - Fasciola hepatica excretory-secretory products (FhESP) induce immunomodulatory
      effects on macrophages. Previously, we demonstrated that these effects are
      dependent on Dectin-1. Therefore, the aim of this study was to determine how this
      affects the CD4 T-cells immune response. We observed that FhESP induce an
      increased expression of PD-L2 in macrophages via Dectin-1. Furthermore, in co
      cultures with CD4 T-cell we observed a suppressive effect on proliferative
      response, down-modulation of IFN-gamma and up-modulation of IL-10 via Dectin-1 on
      macrophages. These results suggest that FhESP induce T-cell anergy via selective
      up-regulation of PD-L2 expression on macrophages in a Dectin-1 dependent way. 

PMID- 25758712
TI  - Morphogenesis of the somatic musculature in Drosophila melanogaster.
AB  - In Drosophila melanogaster, the somatic muscle system is first formed during
      embryogenesis, giving rise to the larval musculature. Later during metamorphosis,
      this system is destroyed and replaced by an entirely new set of muscles in the
      adult fly. Proper formation of the larval and adult muscles is critical for basic
      survival functions such as hatching and crawling (in the larva), walking and
      flying (in the adult), and feeding (at both larval and adult stages). Myogenesis,
      from mononucleated muscle precursor cells to multinucleated functional muscles,
      is driven by a number of cellular processes that have begun to be mechanistically
      defined. Once the mesodermal cells destined for the myogenic lineage have been
      specified, individual myoblasts fuse together iteratively to form syncytial
      myofibers. Combining cytoplasmic contents demands a level of intracellular
      reorganization that, most notably, leads to redistribution of the myonuclei to
      maximize internuclear distance. Signaling from extending myofibers induces
      terminal tendon cell differentiation in the ectoderm, which results in secure
      muscle-tendon attachments that are critical for muscle contraction.
      Simultaneously, muscles become innervated and undergo sarcomerogenesis to
      establish the contractile apparatus that will facilitate movement. The cellular
      mechanisms governing these morphogenetic events share numerous parallels to
      mammalian development, and the basic unit of all muscle, the myofiber, is
      conserved from flies to mammals. Thus, studies of Drosophila myogenesis and
      comparisons to muscle development in other systems highlight conserved regulatory
      programs of biomedical relevance to general muscle biology and studies of muscle
      disease.

PMID- 25758715
TI  - Prevalence of inherited neurotransmitter disorders in patients with movement
      disorders and epilepsy: a retrospective cohort study.
AB  - BACKGROUND: Inherited neurotransmitter disorders are primary defects of
      neurotransmitter metabolism. The main purpose of this retrospective cohort study
      was to identify prevalence of inherited neurotransmitter disorders. METHODS: This
      retrospective cohort study does not have inclusion criteria; rather included all
      patients who underwent cerebrospinal fluid (CSF) homovanillic and 5-hydroxyindol
      acetic acid measurements. Patients with CSF neurotransmitter investigations
      suggestive of an inherited neurotransmitter disorder and patients with normal or
      non-diagnostic CSF neurotransmitter investigations underwent direct sequencing of
      single gene disorders. RESULTS: There were 154 patients between October 2004 and
      July 2013. Four patients were excluded due to their diagnosis prior to this study
      dates. Two major clinical feature categories of patients who underwent lumbar
      puncture were movement disorders or epilepsy in our institution. Twenty out of
      the 150 patients (13.3%) were diagnosed with a genetic disorder including
      inherited neurotransmitter disorders (6 patients) (dihydropteridine reductase, 6
      pyruvoyl-tetrahydropterin synthase, guanosine triphosphate cyclohydrolase I,
      tyrosine hydroxylase, pyridoxine dependent epilepsy due to mutations in the
      ALDH7A1 gene and pyridoxamine-5-phosphate oxidase deficiencies) and non
      neurotransmitter disorders (14 patients). CONCLUSION: Prevalence of inherited
      neurotransmitter disorders was 4% in our retrospective cohort study. Eight out of
      the 150 patients (5.3%) had one of the treatable inherited metabolic disorders
      with favorable short-term neurodevelopmental outcomes, highlighting the
      importance of an early and specific diagnosis. Whole exome or genome sequencing
      might shed light to unravel underlying genetic defects of new inherited
      neurotransmitter disorders in near future.

PMID- 25758717
TI  - Aggrecan nanoscale solid-fluid interactions are a primary determinant of
      cartilage dynamic mechanical properties.
AB  - Poroelastic interactions between interstitial fluid and the extracellular matrix
      of connective tissues are critical to biological and pathophysiological functions
      involving solute transport, energy dissipation, self-stiffening and lubrication.
      However, the molecular origins of poroelasticity at the nanoscale are largely
      unknown. Here, the broad-spectrum dynamic nanomechanical behavior of cartilage
      aggrecan monolayer is revealed for the first time, including the equilibrium and
      instantaneous moduli and the peak in the phase angle of the complex modulus. By
      performing a length scale study and comparing the experimental results to
      theoretical predictions, we confirm that the mechanism underlying the observed
      dynamic nanomechanics is due to solid-fluid interactions (poroelasticity) at the
      molecular scale. Utilizing finite element modeling, the molecular-scale hydraulic
      permeability of the aggrecan assembly was quantified (kaggrecan = (4.8 +/- 2.8) *
      10(-15) m(4)/N.s) and found to be similar to the nanoscale hydraulic permeability
      of intact normal cartilage tissue but much lower than that of early diseased
      tissue. The mechanisms underlying aggrecan poroelasticity were further
      investigated by altering electrostatic interactions between the molecule's
      constituent glycosaminoglycan chains: electrostatic interactions dominated steric
      interactions in governing molecular behavior. While the hydraulic permeability of
      aggrecan layers does not change across species and age, aggrecan from adult human
      cartilage is stiffer than the aggrecan from newborn human tissue. 

PMID- 25758716
TI  - Actin foci facilitate activation of the phospholipase C-gamma in primary T
      lymphocytes via the WASP pathway.
AB  - Wiscott Aldrich Syndrome protein (WASP) deficiency results in defects in calcium
      ion signaling, cytoskeletal regulation, gene transcription and overall T cell
      activation. The activation of WASP constitutes a key pathway for actin filament
      nucleation. Yet, when WASP function is eliminated there is negligible effect on
      actin polymerization at the immunological synapse, leading to gaps in our
      understanding of the events connecting WASP and calcium ion signaling. Here, we
      identify a fraction of total synaptic F-actin selectively generated by WASP in
      the form of distinct F-actin 'foci'. These foci are polymerized de novo as a
      result of the T cell receptor (TCR) proximal tyrosine kinase cascade, and
      facilitate distal signaling events including PLCgamma1 activation and subsequent
      cytoplasmic calcium ion elevation. We conclude that WASP generates a dynamic F
      actin architecture in the context of the immunological synapse, which then
      amplifies the downstream signals required for an optimal immune response. 

PMID- 25758718
TI  - Molecular and Histopathological Study on the Ameliorative Effects of Curcumin
      Against Lead Acetate-Induced Hepatotoxicity and Nephrototoxicity in Wistar Rats.
AB  - Lead (Pb(2+)) toxicity is the most common form of heavy metal intoxication in
      humans and animals. Therefore, the current study was conducted to evaluate the
      potential ameliorative effects of curcumin on lead acetate (LA)-induced
      deleterious effects in the liver and kidney. Forty male Wistar rats were divided
      into four equal groups; first group was used as a control and given both corn oil
      orally and vehicle of lead acetate intraperitoneally (i.p). Groups from 2-4 were
      treated with lead acetate (LA; 50 mg/kg BW i.p), curcumin (200 mg/kg BW orally),
      and curcumin plus lead acetate, respectively. Curcumin was administered 3 weeks
      before LA injection for 7 days. Pb(2+)-intoxicated rats have higher Pb(2+) levels
      compared to other treated groups. Results revealed that lead acetate
      significantly increased the serum levels of hepatic transaminases (GPT and GOT),
      urea and creatinine, while albumin was significantly decreased. In parallel,
      serum IgG, IgM, and IgA were significantly decreased in LA-injected rats. LA
      groups showed decrease in messenger RNA (mRNA) expression of catalase, SOD, GST,
      GPx, and alpha-1 acid glycoprotein (AGP), while the gene expression of desmin,
      vimentin, transforming growth factor-beta1 (TGF-beta1), monocyte chemoattractant
      protein-1 (MCP-1), and alpha-2 macroglobulin (alpha-2M) was increased. Prior and
      coadministration of curcumin with LA for 7 days significantly improved the
      ameliorated changes in liver and kidney, immunoglobulins, and mRNA expression.
      Moreover, curcumin ameliorated LA-induced congestion of hepatic and renal blood
      vessels and decreased fibrous tissue proliferation and necrosis of hepatocytes.
      In the kidney, LA-induced degeneration in tubular epithelium and intraluminal
      hyaline casts and prior curcumin administration restored normal renal structure
      with mild congestion of renal blood vessels. The results clarify the potential of
      curcumin to counteract the immunosuppressive alteration in gene expression as
      well as hepatic and renal damage occurred after Pb(2+) intoxication. 

PMID- 25758720
TI  - Dose- and Time-Dependent In Vitro Effects of Divalent and Trivalent Iron on the
      Activity of Bovine Spermatozoa.
AB  - This in vitro study was designed to assess the impact of divalent (Fe(2+)) or
      trivalent (Fe(3+)) iron on the activity and oxidative balance of bovine
      spermatozoa at specific time intervals (0, 2, 8, 16, and 24 h) during an in vitro
      culture. Forty-five semen samples were collected from adult breeding bulls and
      diluted in physiological saline solution supplemented with different
      concentrations (0, 1, 5, 10, 50, 100, 200, 500, 1000 MUmol/L) of FeCl2 or FeCl3.
      Spermatozoa motion parameters were assessed using the SpermVisionTM computer
      aided sperm analysis (CASA) system. Cell viability was examined with the
      metabolic activity 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide
      (MTT) assay, and the nitroblue-tetrazolium (NBT) test was applied to quantify the
      intracellular superoxide formation. Both divalent and trivalent iron exhibited a
      dose- and time-dependent impact on the spermatozoa physiology and oxidative
      balance. Concentrations >=50 MUmol/L FeCl2 and >=100 MUmol/L FeCl3 led to a
      significant decrease of spermatozoa motility (P < 0.05) and mitochondrial
      activity (P < 0.001 with respect to 200-1000 MUmol/L FeCl2/FeCl3; P < 0.01 in
      case of 100 MUmol/L FeCl2/FeCl3), accompanied by a significant superoxide
      overproduction (P < 0.001 in terms of 200-1000 MUmol/L FeCl2 and 500-1000 MUmol/L
      FeCl3; P < 0.01 with respect to 100 MUmol/L FeCl2 and 100-200 MUmol/L FeCl3). On
      the other hand, concentrations below 10 MUmol/L FeCl2 and 50 MUmol/L FeCl3 proved
      to stimulate the spermatozoa activity, as shown by a significant preservation of
      the motility and viability characteristics (P < 0.001 in case of the motility
      parameters; P < 0.01 with respect to the spermatozoa viability), alongside a
      significant decline of the superoxide generation (P < 0.05). In a direct
      comparison, divalent iron has been shown to be more toxic than trivalent iron.
      Results from this in vitro study show that high concentrations of both forms of
      iron are toxic, while their low concentrations may have spermatozoa activity
      promoting properties. In vitro concentrations of divalent or trivalent iron that
      could be regarded as critical are 50 MUmol/L FeCl2 and 100 MUmol/L FeCl3 when
      iron ceases to be an essential micronutrient in order to become a toxic risk
      factor. 

PMID- 25758719
TI  - Autophagy Mediates Astrocyte Death During Zinc-Potentiated Ischemia--Reperfusion
      Injury.
AB  - Pathological release of excess zinc ions and the resultant increase in
      intracellular zinc has been implicated in ischemic brain cell death, although the
      underlying mechanisms are not fully understood. Since zinc promotes the formation
      of the autophagic signal, reactive oxygen species (ROS), and increases autophagy,
      a known mechanism of cell death, we hypothesized that autophagy is involved in
      zinc-induced hypoxic cell death. To study this hypothesis, we determined the
      effect of zinc on autophagy and ROS generation in C8-D1A astrocytes subjected to
      hypoxia and rexoygenation (H/R), simulating ischemic stroke. C8-D1A astrocytes
      subjected to 3-h hypoxia and 18-h reoxygenation exhibited dramatically increased
      autophagy and astrocyte cell death in the presence of 100 MUM zinc.
      Pharmacological inhibition of autophagy decreased zinc-potentiated H/R-induced
      cell death, while scavenging ROS reduced both autophagy and cell death caused by
      zinc-potentiated H/R. These data indicate that zinc-potentiated increases in ROS
      lead to over-exuberant autophagy and increased cell death in H/R-treated
      astrocytes. Furthermore, our elucidation of this novel mechanism indicates that
      modulation of autophagy, ROS, and zinc levels may be useful targets in decreasing
      brain damage during stroke.

PMID- 25758721
TI  - Dietary Chitosan Supplementation Ameliorates Isoproterenol-Induced Aberrations in
      Membrane-Bound ATPases and Mineral Status of Rat Myocardium.
AB  - Myocardial infarction is one of the major public concerns in both developed and
      developing countries. Recently, there is growing interest in potential healthcare
      applications of marine natural products in the field of cardiovascular research.
      In the present study, we have examined the membrane-stabilizing potential of
      marine mucopolysaccharide-chitosan in modulating the aberrations of thiol
      dependent membrane-bound ATPases activities, mineral status, and cardiac
      diagnostic markers in isoproterenol-induced myocardial infarction condition in
      rats. Dietary intake of chitosan significantly (p < 0.05) counteracted the
      isoproterenol-induced lipid peroxidation and maintained the levels of thiol
      contents and cardiac biomarkers at concentrations analogous to that of normal
      controls in the rat myocardium. Chitosan administration also significantly
      mitigated isoproterenol-induced aberrations in the membrane-bound ATPase
      activities in the heart tissue and preserved the myocardial mineral status in
      serum and heart tissue of experimental rats at near normal value. The results of
      the present study have indicated that the salubrious effect of dietary chitosan
      supplementation in attenuating the experimentally induced myocardial infarction
      condition is probably ascribable to its antioxidant defense and membrane
      stabilizing properties. 

PMID- 25758722
TI  - Association of Serum Heavy Metals and Trace Element Concentrations with
      Reproductive Hormone Levels and Polycystic Ovary Syndrome in a Chinese
      Population.
AB  - To investigate the serum concentrations of 11 heavy metals and trace elements in
      patients with polycystic ovary syndrome (PCOS). A total of 369 women (including
      96 patients with PCOS) were studied. No differences with statistical significance
      in the median barium, cadmium, lead, arsenic, chromium, gallium, strontium, and
      vanadium concentrations were observed between the patients with PCOS and the
      control group. Serum nickel (Ni) (P = 0.000) and copper (Cu) (P = 0.000) levels
      were significantly higher, but zinc (Zn) levels (P = 0.009) were significantly
      lower in patients with PCOS compared with the control group. The results of the
      association between metal levels and hormone levels indicated that Ni, Cu, and Zn
      may play a role in the pathogenesis of PCOS related with reproductive hormone
      levels. The findings in the present study should be investigated with further
      trials in order to obtain new insights into PCOS. 

PMID- 25758723
TI  - Emplementation of National Iron Plus Initiative for child health: challanges
      ahead.

PMID- 25758724
TI  - Prevalence of depression and associated risk factors among the elderly in urban
      and rural field practice areas of a tertiary care institution in Ludhiana.
AB  - BACKGROUND: Depression, the most common psychiatric disorder among the elderly,
      is not yet perceived as an important health problem in India, where few
      population-based studies have addressed this problem. OBJECTIVES: To estimate the
      prevalence of depression and identify the associated risk factors in the elderly
      population. MATERIALS AND METHODS: 3038 consenting elderly (>60 years old) rural
      and urban residents of both sexes from the field practice areas were interviewed
      and examined in a cross-sectional study. Physical impairment in the subjects was
      assessed with the Everyday Abilities Scale for India (EASI), depression by the 15
      item Geriatric Depression Scale (GDS-15), and cognitive impairment by the Mini
      Mental State Examination (MMSE). Data were analyzed using Epi Info version-6
      software. Statistical analysis included proportions, chi[2] -test, odds ratio,
      and its 95% confidence interval. Multiple logistic regression was done using SPSS
      version 21. RESULTS: The prevalence of depression in the study population was
      8.9%. It was significantly higher in urban residents, females, older elderly,
      nuclear families, in those living alone, those not working, illiterates, poor,
      functionally impaired, and cognitively impaired. In the multivariate analysis,
      unmarried/widowed status, unemployment, and illiteracy did not emerge as risk
      factors. CONCLUSIONS: Urban residence, female gender, higher age, nuclear family,
      poverty, and functional and cognitive impairment were found to be associated with
      depression even after controlling for other factors.

PMID- 25758725
TI  - Inequity in awareness and utilization of adolescent reproductive and sexual
      health services in union territory, Chandigarh, North India.
AB  - BACKGROUND: Adolescents are a heterogeneous, vulnerable, and sexually active
      group. Geographical and educational health disparities exist among urban, rural,
      and slum adolescents and among out-of-school and school-going adolescents,
      respectively. Adolescent reproductive and sexual health (ARSH) services should be
      implemented in a manner to minimize health inequities among them. OBJECTIVES: To
      ascertain the extent of awareness and utilization of ARSH services provided under
      reproductive and child health(RCH) program among adolescents in Chandigarh.
      MATERIALS AND METHODS: A cross-sectional study was conducted among 854
      adolescents (402 household, 200 out-of-school, and 252 school-going adolescents)
      in Chandigarh using pretested validated interview schedule on awareness and
      utilization of adolescent reproductive and sexual health services from February
      to April 2011 in North Indian Union Territory of Chandigarh. Ordinal regression
      analysis was done to study the association of socio-demographic variables with
      awareness and utilization of ARSH. Results: Awareness about contraception and
      health services was significantly less among rural (12.7% and 1.1%, respectively)
      adolescents as compared to slum (17.9% and 4.6%, respectively) and urban
      adolescents (33.5% and 7.8%, respectively) (P < 0.05). Out-of-school adolescents
      were utilizing the preventive [odds ratio (OR) 0.39, P < 0.001] and curative
      services significantly lesser (OR = 0.54, P < 0.001) and had higher substance
      abuse (OR = 4.26, P= 0.006). Awareness was significantly associated with older
      age of adolescents (OR = 4.4,P < 0.001), poor education of father (OR = 0.5, P =
      0.002), rural area (OR = 0.56, P = 0.001), and out-of-school status (OR = 0.35, P
      < 0.001). CONCLUSION: Awareness and utilization of ARSH services was inequitable
      and was more among urban and school-going adolescents. Educational status was the
      most important factor affecting it.

PMID- 25758726
TI  - Identifying psychological distress in elderly seeking health care.
AB  - BACKGROUND: Psychological distress in the elderly with various illness conditions
      often goes unrecognized. Since psychological distress is treatable, it is
      important to recognize it at the earliest to enhance recovery. This is an interim
      analysis of screening data of the elderly seeking health care in a hospital in
      India, with a focus on the 12-item General Health Questionnaire (GHQ-12), a
      screening instrument for psychological distress and a rationale for a higher
      cutoff score in help seeking elderly. MATERIALS AND METHODS: A retrospective
      analysis of screening data of psychological distress using GHQ-12 in the elderly
      seeking care for neuropsychiatric conditions was carried out. Traditionally, >=2
      is considered positive for distress by GHQ-12. Receiver Operating Characteristic
      (ROC) curve was used to define new cutoff points for psychological distress.
      RESULTS: At >=2, 2443 (50%) of the elderly screened were recognized to be
      psychologically distressed. Using an ROC and optimum sensitivity and specificity
      measures, a cutoff score of >=4 was observed to detect 30% of the elderly who had
      diagnosable mental health disorders. Female sex, illiteracy, and multiple co
      morbidities were the factors that were associated with higher cutoff scores on
      GHQ-12 proposed here and psychiatric morbidity thereof. CONCLUSION: There is
      greater psychological distress among the elderly seeking health care. Hence, it
      is important to screen them and identify those at higher risk. Using a higher
      cutoff score with a standardized instrument like GHQ-12 indicated that it was
      statistically valid to identify those elderly with higher distress in a busy out
      patient setting.

PMID- 25758727
TI  - Assessment of oral mucosal lesions among eunuchs residing in Bhopal city, Madhya
      Pradesh, India: a cross-sectional study.
AB  - AIM: The present cross-sectional study following the STROBE guidelines was
      conducted to assess the prevalence of oral mucosal lesions among males, females,
      and eunuchs residing in Bhopal city, Madhya Pradesh India. MATERIALS AND METHODS:
      Based on convenient non-probability snowball sampling technique, all the self
      identified eunuchs residing in the city of Bhopal who were present at the time of
      examination and who fulfilled the selection criteria were examined. A cross
      section of the general population (males and females) residing in the same
      locality where these eunuchs live was also examined. The World Health
      Organization (WHO) oral health assessment proforma (1997) was used to collect the
      information on oral mucosal lesions. All the obtained data were analyzed by using
      a Statistical Package for Social Sciences version 20. RESULTS: Overall prevalence
      of oral mucosal lesions was 127 (19.9%) among the study subjects. Fifty-nine
      (28.5%) eunuchs, 56 (25.7%) males, and 12 (5.6%) females were observed to have
      some oral mucosal lesions. Oral submucous fibrosis (6.4%), leukoplakia (5.5%),
      and traumatic ulceration (4.2%) were the major oral mucosal conditions observed.
      CONCLUSION: The information presented in this study adds to our understanding of
      the common oral mucosal lesions occurring in the eunuch population. Efforts to
      increase patient awareness of the oral effects of tobacco use and to eliminate
      the habit are needed to improve the oral and general health of eunuchs.

PMID- 25758728
TI  - Prevalence and determinants of sexually transmitted infections (STIs) among male
      migrant factory workers in Haryana, North India.
AB  - BACKGROUND: Male migrant workers display high risk sexual behavior and have been
      shown to have higher prevalence of sexually transmitted infections (STIs), which
      make them more vulnerable to HIV infection. We aimed to estimate the prevalence
      of self-reported STIs and delineate their determinants among male migrant factory
      workers in Faridabad, Haryana. MATERIALS AND METHODS: Male workers in two
      selected factories, who were aged >=18 years, were born outside Haryana
      (destination), and who had migrated to Haryana after the age of 15 years were
      eligible. Socio-demographic information, HIV/AIDS knowledge and behavior, and
      self-reported STI symptoms in the last 1 year were ascertained by face-to-face
      interview. Determinants of STIs were identified by regression analysis. RESULTS:
      Totally 755 eligible workers participated. Mean +/- SD age was 31.4 +/- 8.2 years
      and migration duration was 9.5 +/- 6.7 years. At least one STI symptom was
      reported by 41.7% of the participants (burning micturition- 35%, inguinal bubos
      5.2%, genital ulcers- 2.6%, urethral pus discharge- 1.3%). Factors associated
      with STIs were higher age at migration, lower HIV/AIDS knowledge, paid sex in the
      last year, non-use of condoms during the last non-spousal sex, and unfavorable
      intention to use condom. CONCLUSION: Prevalence of self-reported STIs among these
      migrant men was high. Targeted Interventions among migrant workers need to be
      strengthened for control and prevention of STIs.

PMID- 25758729
TI  - Mobile phones: time to rethink and limit usage.
AB  - Radiofrequency waves generated from mobile phones cause potential public health
      problems. Short-term effects like changes in sleep, heart rate, and blood
      pressure, and long-term effects like carcinoma are well documented. The
      Government of India's efforts in laying down regulations regarding the safety
      limits, manufacture, marketing, and mobile use are still in nascent stage. The
      need for stringent enforcement of laws for prevention of phone usage while
      driving and guidelines of medical regulatory bodies regarding rules and
      regulations of phone usage while at class or attending patients is of utmost
      importance. This should be supplemented by mass media to raise awareness among
      people regarding the possible health effects of radiofrequency emissions from
      mobile phones and the guidelines to minimize its exposure. It is the need of the
      hour to teach young people to be structured, to know when to have the cell phone
      on, and to avoid becoming the slave of technology instead of its mastery. 

PMID- 25758730
TI  - Updated BG Prasad socioeconomic classification, 2014: a commentary.
AB  - Modified BG Prasad socioeconomic scale is widely used to determine the
      socioeconomic status of study subjects in health studies in India. It is an
      income-based scale and, therefore, has to be constantly updated to take inflation
      and depreciation of rupee into account. The Consumer Price Index (CPI) for
      industrial workers (IW) is used to calculate updated income categories for
      January 2014. Details of the calculations involved will enable young researchers
      to calculate specific income categories for their research work. State-specific
      CPI values are also available on the Department of Labour website and should be
      used to determine more accurate income categories for the study area. 

PMID- 25758731
TI  - Risk factors for cancer cervix among rural women of a hilly state: a case-control
      study.
AB  - In Himachal Pradesh, cancer cervix is a major public health problem since it
      ranks as the number one female cancer. A case-control study of 226 newly
      diagnosed, histopathologically confirmed cases of cancer cervix and equal number
      of matched controls was conducted at Regional Cancer Center, Himachal Pradesh
      during the period from July 2008 to October 2009 with the objective to study the
      common factors associated with cancer cervix. Univariate analysis identified 10
      risk factors associated significantly with the disease. On multiple logistic
      regression, however, only seven risk factors were found to be associated
      significantly with the disease. These were: Age at birth of first child, spacing
      between two children, age at marriage, literacy, socioeconomic status,
      multiparity, and poor genital hygiene. Risk factors such as poor genital hygiene,
      age at birth of first child <19 years, early marriage, illiteracy, multiparity,
      and low socioeconomic status were highly prevalent in the study subjects and were
      found to be significantly associated with cancer cervix. 

PMID- 25758732
TI  - Desirable factors for maintaining normal BMI of urban affluent women of Delhi.
AB  - The study aimed to identify desirable social, familial, reproductive, dietary,
      and lifestyle factors for maintaining normal body mass index (BMI) of urban
      affluent women (25-45 years) in Delhi, India. A total of 387 urban affluent women
      with at least one living child participated in this cross-sectional study
      conducted from March 2008 to April 2010. Women were classified into four BMI
      categories on the basis of World Health Organization (WHO; 2004) classification
      for Asians. Significant factors for maintaining normal BMI were: Younger age,
      less parity, nuclear family, normal weight status of parents, postpartum weight
      gain between 2 and 3 kg, regularity in taking meals, fixed meal size, self
      perceived normal weight, and shorter sitting time and television viewing time.
      Multivariate regression analysis identified five determining factors for
      maintaining BMI, which are normal weight of father, self-perceived normal weight,
      fixed meal size, sitting time less than 6 h/day, and television viewing time less
      than 1 h/day. By small lifestyle modifications, normal BMI can be maintained. 

PMID- 25758733
TI  - A study on the effect of Janani Suraksha Yojana on antenatal registration and
      institutional deliveries in the Agra district of Uttar Pradesh.
AB  - Janani Suraksha Yojana (JSY) was launched in April 2005, to promote institutional
      deliveries through provision of cash assistance, transport, escort, and referral
      services. An observational cross-sectional study was conducted to assess the
      antenatal registrations, postnatal checkups, and institutional deliveries, and to
      compare the various social groups. Married women of the reproductive age group,
      having at least two children, were interviewed regarding antenatal care,
      delivery, and postnatal care in both pregnancies, latest as well as previous.
      Post JSY implementation, antenatal registrations increased from 61.79 to 96.34%,
      Deliveries at the Government Health Facility increased from 25.20 to 53.25% and
      postnatal check-ups increased from 45.93 to 69.51%. In the post-JSY
      implementation phase, the Government Health Facility was preferred more by
      Scheduled Castes (SC), Scheduled Tribes (ST), Other Backward Classes (OBC) (SC/ST
      = 56.87%, OBC = 60.2%, and general = 43.68%), educated (Illiterate = 17.39%,
      Primary = 88.14, and Middle or above = 81.94%) and the lower socioeconomic
      classes (Lower SEC 71.83% and Upper lower and above = 45.71%) for their
      deliveries. It appears that the socially backward groups have benefited more from
      JSY. 

PMID- 25758734
TI  - Compliance to anti-rabies vaccination in post-exposure prophylaxis.
AB  - Complete post-exposure prophylaxis is necessary to prevent rabies among all
      animal bite victims. It is essential for the bite victims to complete the full
      course of vaccination as recommended for complete protection. The present study
      was conducted to determine the compliance rate for anti-rabies vaccination by
      both intramuscular route and intradermal route and to determine the major
      constraints. The study was done at two municipal corporation hospitals in
      Bangalore, India. The compliance rate for intramuscular rabies vaccination was
      60.0% and for intradermal rabies vaccination 77.0%. The major constraints were
      loss of wages, forgotten dates, cost incurred and distance from the hospital.
      Hence, the present study showed that the compliance to anti-rabies vaccination
      for post-exposure prophylaxis is low and is a cause of concern, as animal bite
      victims who do not complete the full course of vaccination are still at risk of
      developing rabies. 

PMID- 25758736
TI  - Psychological morbidity among undergraduate medical students.

PMID- 25758735
TI  - Anthropometric and behavioral risk factor for non-communicable diseases: a
      cluster survey from rural Wardha.
AB  - Monitoring of risk factors for non-communicable diseases (NCDs) over a period of
      time would be useful to make an indirect assessment of the actual disease burden.
      A cross-sectional survey was done among males aged 15-64 years, to study the
      prevalence of anthropometric and behavioral risk factors of NCDs. Information was
      collected on the sociodemographical factors, tobacco use, alcohol intake, diet,
      salt consumption, and physical activity, using a predesigned and pretested
      interview schedule. Anthropometric measurements were taken. A study found that
      prevalence of current smoking and use of smokeless tobacco was 14.2 and 54.9%,
      respectively. Alcohol intake was present in 22.7% of the study population. Per
      capita salt consumption per day was 14.6 g. A sedentary lifestyle was present
      among 19% of the men. Prevalence of overweight and obesity was 8.8% and 9.5%,
      respectively. Our finding suggested that greater surveillance of the NCD risk
      factors should be initiated as early as possible, in parallel with surveillance
      for communicable diseases. 

PMID- 25758737
TI  - Importance of Mediclaim policies covering congenital anomalies in India.

PMID- 25758738
TI  - Implementation of ICD 10: a study on the doctors' knowledge and coding practices
      in Delhi.

PMID- 25758739
TI  - Are confounders important in a study?

PMID- 25758740
TI  - Infectious agents and acute myocardial infarction.

PMID- 25758741
TI  - Prize winning essays: undergraduate submissions to road to ISMoPH- environment -
      agenda for health promotion.

PMID- 25758742
TI  - Clinical efficacy and safety of cilostazol: a critical review of the literature.
AB  - Cilostazol is a unique antiplatelet agent that has been commercially available
      for over two decades. As a phosphodiesterase III inhibitor, it reversibly
      inhibits platelet aggregation yet also possesses vasodilatory and
      antiproliferative properties. It has been widely studied in a variety of disease
      states, including peripheral arterial disease, cerebrovascular disease, and
      coronary artery disease with percutaneous coronary intervention. Overall,
      cilostazol appears to be a promising agent in the management of these disease
      states with a bleeding profile comparable to placebo; even when combined with
      other antiplatelet agents, cilostazol does not appear to increase the rate of
      bleeding. Despite the possible benefit of cilostazol, its use is limited by
      tolerability as some patients often report drug discontinuation due to headache,
      diarrhea, dizziness, or increased heart rate. To date, it has been predominantly
      studied in the Asian population, making it difficult to extrapolate these results
      to a more diverse patient population. This paper discusses the evolving role of
      cilostazol in the treatment of vascular diseases. 

PMID- 25758743
TI  - Cotton QTLdb: a cotton QTL database for QTL analysis, visualization, and
      comparison between Gossypium hirsutum and G. hirsutum * G. barbadense
      populations.
AB  - KEY MESSAGE: A specialized database currently containing more than 2200 QTL is
      established, which allows graphic presentation, visualization and submission of
      QTL. In cotton quantitative trait loci (QTL), studies are focused on
      intraspecific Gossypium hirsutum and interspecific G. hirsutum * G. barbadense
      populations. These two populations are commercially important for the textile
      industry and are evaluated for fiber quality, yield, seed quality, resistance,
      physiological, and morphological trait QTL. With meta-analysis data based on the
      vast amount of QTL studies in cotton it will be beneficial to organize the data
      into a functional database for the cotton community. Here we provide a tool for
      cotton researchers to visualize previously identified QTL and submit their own
      QTL to the Cotton QTLdb database. The database provides the user with the option
      of selecting various QTL trait types from either the G. hirsutum or G. hirsutum *
      G. barbadense populations. Based on the user's QTL trait selection, graphical
      representations of chromosomes of the population selected are displayed in
      publication ready images. The database also provides users with trait information
      on QTL, LOD scores, and explained phenotypic variances for all QTL selected. The
      CottonQTLdb database provides cotton geneticist and breeders with statistical
      data on cotton QTL previously identified and provides a visualization tool to
      view QTL positions on chromosomes. Currently the database (Release 1) contains
      2274 QTLs, and succeeding QTL studies will be updated regularly by the curators
      and members of the cotton community that contribute their data to keep the
      database current. The database is accessible from http://www.cottonqtldb.org.

PMID- 25758744
TI  - Heritability of racing durability traits in the Australian and Hong Kong
      Thoroughbred racing populations.
AB  - REASONS FOR PERFORMING STUDY: Many attempts have been made to improve the well
      being of racing Thoroughbreds through improvements in management and veterinary
      care. However, these attempts are often limited by the industry's ability to
      regulate a large number of environmental variables and as a result have arguably
      had limited success in providing long-lasting change for the breed. OBJECTIVES:
      To identify heritable durability traits for Thoroughbred horses racing in
      Australia and Hong Kong. STUDY DESIGN: Heritability analysis of a longitudinal
      dataset. METHODS: Performance data on the Thoroughbred populations racing in
      Australia and Hong Kong between 2000 and 2011 (n = 168,993) were used to estimate
      the heritabilities and probability values of fixed effects and covariates for a
      range of racing durability traits. Heritabilities for all durability traits were
      estimated using a single trait animal model. Each model included, as a minimum,
      the effects of sex and trainer. RESULTS: Racing longevity (0.12 +/- 0.01), racing
      persistence (0.10 +/- 0.01), racing frequency (0.03 +/- 0.01), spells (a time
      period between consecutive races, official trials and/or jump-outs greater than
      90 days in length) per year (0.05 +/- 0.01), spells per 10 starts (0.03 +/- 0.01)
      and variation of days between races (0.08 +/- 0.03) were all significantly
      heritable for horses racing in Australia. Racing longevity (0.08 +/- 0.02),
      racing persistence (0.04 +/- 0.02), spells per year (0.06 +/- 0.02) and spells
      per 10 starts (0.11 +/- 0.04) were significantly heritable for horses racing in
      Hong Kong. CONCLUSIONS: The heritabilities estimated for durability traits in
      this study provide support for the successful and practical application of
      genetic selection methodologies to improving the well-being of racing
      Thoroughbreds.

PMID- 25758745
TI  - The 'sialo-microbial-dental complex' in oral health and disease.
AB  - Biofilms are naturally found in all wet environments including the oral
      structures of nearly all species. Human oral biofilms have existed since our
      earliest ancestors and have evolved symbiotically with the dentition over many
      millennia within a Palaeolithic, hunter-gatherer setting. Irrespective of the
      plant-animal ratio, it can be argued that the Palaeolithic diet was essentially
      acidic, and acted as a selective force for much of the evolution of the
      stomatognathic system. The relationship between saliva, biofilm and teeth, the
      'sialo-microbial-dental complex', provides oral health benefits and offers a
      different perspective to the old dental paradigm that only associated oral
      biofilms (plaque) with disease (caries). This new paradigm emphasises that oral
      biofilms are essential for the 'mineral maintenance' of teeth. Oral biofilms
      provide physical protection from dietary acid and together with bacterial
      metabolic acids cause the resting pH of the biofilm to fall below neutral. This
      is then followed by the re-establishment of a neutral environment by chemical
      interactions mediated by the saliva within the biofilm. Such pH fluctuations are
      often responsible for the cyclic demineralisation, then remineralisation of
      teeth, a process necessary for tooth maturation. However, since the advent of
      farming and especially since the industrial revolution, the increase in
      consumption of carbohydrates, refined sugars and acidic drinks has changed the
      ecology of biofilms. Biofilm biodiversity is significantly reduced together with
      a proliferation of acidogenic and aciduric organisms, tipping the balance of the
      'demin-remin' cycle towards net mineral loss and hence caries. In addition, the
      consumption of acidic drinks in today's societies has removed the protective
      nature of the biofilm, leading to erosion. Erosion and caries are 'modern-day'
      diseases and reflect an imbalance within the oral biofilm resulting in the
      demineralisation of teeth. 

PMID- 25758747
TI  - Biopsy versus resection in the management of high-grade gliomas in the elderly.

PMID- 25758746
TI  - Phase 2 trial of dasatinib in target-selected patients with recurrent
      glioblastoma (RTOG 0627).
AB  - BACKGROUND: We conducted a phase II trial to evaluate the efficacy of dasatinib,
      a multitargeted tyrosine kinase inhibitor, for adults with recurrent glioblastoma
      (GBM). METHODS: Eligibility requirements were Karnofsky performance status >=
      60%; no concurrent hepatic enzyme-inducing anticonvulsants; prior treatment with
      surgery, radiotherapy, and temozolomide exclusively; and activation or
      overexpression of >= 2 putative dasatinib targets in GBM (ie, SRC, c-KIT, EPHA2,
      and PDGFR). Using a 2-stage design, 77 eligible participants (27 in stage 1, if
      favorable, and then 50 in stage 2) were needed to detect an absolute improvement
      in the proportion of patients either alive and progression-free patients at 6
      months (6mPFS) or responding (any duration) from a historical 11% to 25%.
      RESULTS: A high rate of ineligibility (27%) to stage 1 precluded a powered
      assessment of efficacy, but there was also infrequent treatment-related toxicity
      at 100 mg twice daily. Therefore, the study was redesigned to allow intrapatient
      escalation by 50 mg daily every cycle as tolerated (stage 1B) before determining
      whether to proceed to stage 2. Escalation was tolerable in 10 of 17 (59%)
      participants evaluable for that endpoint; however, among all eligible patients
      (stages 1 and 1B, n = 50), there were no radiographic responses, median overall
      survival was 7.9 months, median PFS was 1.7 months, and the 6mPFS rate was 6%.
      The clinical benefit was insufficient to correlate tested biomarkers with
      efficacy. The trial was closed without proceeding to stage 2. CONCLUSIONS:
      Intraparticipant dose escalation was feasible, but dasatinib was ineffective in
      recurrent GBM. Clinical trials.gov identified. NCT00423735 (available at
      http://clinicaltrials.gov/ct2/show/NCT00423735).

PMID- 25758749
TI  - Biologically inspired band-edge laser action from semiconductor with dipole
      forbidden band-gap transition.
AB  - A new approach is proposed to light up band-edge stimulated emission arising from
      a semiconductor with dipole-forbidden band-gap transition. To illustrate our
      working principle, here we demonstrate the feasibility on the composite of SnO2
      nanowires (NWs) and chicken albumen. SnO2 NWs, which merely emit visible defect
      emission, are observed to generate a strong ultraviolet fluorescence centered at
      387 nm assisted by chicken albumen at room temperature. In addition, a stunning
      laser action is further discovered in the albumen/SnO2 NWs composite system. The
      underlying mechanism is interpreted in terms of the fluorescence resonance energy
      transfer (FRET) from the chicken albumen protein to SnO2 NWs. More importantly,
      the giant oscillator strength of shallow defect states, which is served orders of
      magnitude larger than that of the free exciton, plays a decisive role. Our
      approach therefore shows that bio-materials exhibit a great potential in
      applications for novel light emitters, which may open up a new avenue for the
      development of bio-inspired optoelectronic devices.

PMID- 25758748
TI  - Growth dynamics of untreated glioblastomas in vivo.
AB  - BACKGROUND: Glioblastomas are primary malignant brain tumors with a dismal
      prognosis. Knowledge of growth rates and underlying growth dynamics is useful for
      understanding basic tumor biology, developing realistic tumor models, and
      planning treatment logistics. METHODS: By using repeated pretreatment contrast
      enhanced T1-weighted MRI scans from 106 patients (aged 26-83 years), we studied
      the growth dynamics of untreated glioblastomas in vivo. Growth rates were
      calculated as specific growth rates and equivalent volume doubling times. The fit
      of different possible growth models was assessed using maximum likelihood
      estimations. RESULTS: There were large variations in growth rates between
      patients. The median specific growth rate of the tumors was 1.4% per day, and the
      equivalent volume doubling time was 49.6 days. Exploring 3 different tumor growth
      models showed similar statistical fit for a Gompertzian growth model and a linear
      radial growth model and worse fit for an exponential growth model. However, large
      tumors had significantly lower growth rates than smaller tumors, supporting the
      assumption that glioblastomas reach a plateau phase and thus exhibit Gompertzian
      growth. CONCLUSION: Based on the fast growth rate of glioblastoma shown in this
      study, it is evident that poor treatment logistics will influence tumor size
      before surgery and can cause significant regrowth before adjuvant treatment.
      Since there is a known association between tumor volume, extent of surgical
      resection, and response to adjuvant therapy, it is likely that waiting times play
      a role in patient outcomes.

PMID- 25758750
TI  - Preliminary evaluation of [18F]AlF-NOTA-MAL-Cys39-exendin-4 in insulinoma with
      PET.
AB  - BACKGROUND: High expression of glucagon-like peptide-1 receptor (GLP-1R) in
      insulinoma supplies a potential drug target for tumor imaging. Exendin-4 can
      specifically bind to GLP-1R as an agonist and its analogs are extensively used in
      receptor imaging studies. PURPOSE: A new GLP-1R imaging agent, [(18)F]AlF-NOTA
      MAL-Cys(39)-exendin-4, was designed and prepared for insulinoma imaging. METHODS:
      Cys(39)-exendin-4 was conjugated with NOTA-MAL, then the compound was
      radiolabeled with [(18)F]AlF complex to obtained [(18)F]AlF-NOTA-MAL-Cys(39)
      exendin-4. The tumor-targeting characters of the tracer were evaluated in INS-1
      cells and BALB/c nude mice models. RESULTS: [(18)F]AlF-NOTA-MAL-Cys(39)-exendin-4
      can be efficiently produced with a yield of 17.5 +/- 3.2% (non-decay corrected)
      and radiochemical purity of >95%. The IC50 value of displacement [(18)F]AlF-NOTA
      MAL-Cys(39)-exendin-4 with Cys(39)-exendin-4 was 13.52 +/- 1.36 nM. PET images
      showed excellent tumor visualization with high uptake (9.15 +/- 1.6%ID/g at 30
      min and 7.74 +/- 0.87%ID/g at 60 min). The tumor to muscle, pancreas and liver
      ratios were 63.25, 3.85 and 7.29 at 60 min after injection. GLP-1R binding
      specificity was demonstrated by co-injection with an excess of unlabeled Cys(39)
      exendin-4 and the tumor uptake was found to be reduced significantly. CONCLUSION:
      [(18)F]AlF-NOTA-MAL-Cys(39)-exendin-4 shows favorable characteristics for
      insulinoma imaging and may be translated to clinical studies.

PMID- 25758751
TI  - Nanotechnology-mediated nose to brain drug delivery for Parkinson's disease: a
      mini review.
AB  - Nose to brain delivery of neurotherapeutics have been tried by several
      researchers to explore the virtues of this route viz. circumvention of BBB,
      avoidance of hepatic metabolism, practicality, safety, ease of administration and
      non-invasiveness. Nanoparticle (NP) therapeutics is an emerging modality for the
      treatment of Parkinson's disease (PD) as it offers targeted delivery and enhances
      the therapeutic efficacy and/or bioavailability of neurotherapeutics. This review
      presents a concise incursion into the nanomedicines suitable for PD therapy
      delivered via naso-brain transport. Clinical signs of PD, its pathophysiology,
      specific genetic determinants, diagnosis and therapy involved have been hashed
      out. Properties of brain-targeting NPs, transport efficacy and various
      nanocarriers developed so far also been furnished. In our opinion, nanotechnology
      enabled naso-brain drug delivery is an excellent means of delivering
      neurotherapeutics and is a promising avenue for researchers to develop new
      formulations for the effective management of PD. 

PMID- 25758752
TI  - Insight into the key interactions of bromodomain inhibitors based on molecular
      docking, interaction fingerprinting, molecular dynamics and binding free energy
      calculation.
AB  - The bromodomain is a key protein-protein interaction module that specifically
      reads the acetylation marks of histones in epigenetic regulation. Currently, lots
      of inhibitors targeting the bromodomain have been reported as therapeutic agents.
      To better understand the interaction mechanism of bromodomain inhibitors, 20
      diverse bromodomain inhibitors were studied using a combination of computational
      methods, including molecular docking, interaction fingerprinting, molecular
      dynamics simulation and binding free energy calculation. As a result,
      interactions important for the activity were critically analyzed, and the energy
      contribution in terms of individual residues was explored. These integrated
      results provided insights into two hot spots in the active site of the
      bromodomain, where the hydrophobic hot spot formed by Trp81, Val87, Leu92 and
      Ile146 played a central role in the interaction, and the hydrogen-bond hot spot
      mediated by Asn140 exhibited a moderate contribution to the binding affinity of
      the bromodomain inhibitors. This interaction mechanism study may facilitate the
      rational design of novel small-molecule bromodomain inhibitors. 

PMID- 25758753
TI  - A Modelling Framework for Gene Regulatory Networks Including Transcription and
      Translation.
AB  - Qualitative models of gene regulatory networks have generally considered
      transcription factors to regulate directly the expression of other transcription
      factors, without any intermediate variables. In fact, gene expression always
      involves transcription, which produces mRNA molecules, followed by translation,
      which produces protein molecules, which can then act as transcription factors for
      other genes (in some cases after post-transcriptional modifications). Suppressing
      these multiple steps implicitly assumes that the qualitative behaviour does not
      depend on them. Here we explore a class of expanded models that explicitly
      includes both transcription and translation, keeping track of both mRNA and
      protein concentrations. We mainly deal with regulation functions that are steep
      sigmoids or step functions, as is often done in protein-only models. We find that
      flow cannot be constrained to switching domains, though there can still be
      asymptotic approach to singular stationary points (fixed points in the vicinity
      of switching thresholds). This avoids the thorny issue of singular flow, but
      leads to somewhat more complicated possibilities for flow between threshold
      crossings. In the infinitely fast limit of either mRNA or protein rates, we find
      that solutions converge uniformly to solutions of the corresponding protein-only
      model on arbitrary finite time intervals. This leaves open the possibility that
      the limit system (with one type of variable infinitely fast) may have different
      asymptotic behaviour, and indeed, we find an example in which stability of a
      fixed point in the protein-only model is lost in the expanded model. Our results
      thus show that including mRNA as a variable may change the behaviour of
      solutions. 

PMID- 25758754
TI  - Effects of CCN1 and Macrophage Content on Glioma Virotherapy: A Mathematical
      Model.
AB  - Oncolytic virus (OV) is a genetically engineered virus that can selectively
      replicate in and kill tumor cells while not harming normal cells. OV therapy has
      been explored as a treatment for numerous cancers including glioblastoma, an
      aggressive and devastating brain tumor. Experiments show that extracellular
      matrix protein CCN1 limits OV therapy of glioma by orchestrating an antiviral
      response and enhancing the proinflammatory activation and migration of
      macrophages. Neutralizing CCN1 by antibody has been demonstrated to improve OV
      spread and tends to increase the time to disease progression. In this paper, we
      develop a mathematical model to investigate the effects of CCN1 on the treatment
      of glioma with oncolytic herpes simplex virus. We show that numerical simulations
      of the model are in agreement with the experimental results and then use the
      model to explore the anti-tumor effects of combining antibodies with OV therapy.
      Model simulations suggest that the macrophage content of the tumor is a critical
      factor to the success of OV therapy and to the reduction in tumor volume gained
      with the CCN1 antibody. 

PMID- 25758755
TI  - One pot synthesis of diarylfurans from aryl esters and PhI(OAc)2 via palladium
      associated iodonium ylides.
AB  - The example of palladium-catalyzed intermolecular cyclization for the synthesis
      of various diarylfurans in which one of the aromatic rings originates from the
      phenolic part of the starting ester and the other one from PhI(OAc)2 has been
      reported. The reaction is carried out through two steps: the rearrangement of
      palladium-associated iodonium ylides to form o-iodo diaryl ether and then
      palladium catalyzed intramolecular direct arylation. This reaction can tolerate a
      variety of functional groups and is alternative or complementary to the previous
      methods for the synthesis of diarylfurans. 

PMID- 25758756
TI  - Isolated and syndromic brachydactylies: Diagnostic value of hand X-rays.
AB  - Brachydactyly, or shortening of the digits, is due to the abnormal development of
      phalanges, metacarpals and/or metatarsals. This congenital malformation is
      common, easily detectable clinically but often requires additional radiological
      exploration. Radiographs are essential to characterize the type of brachydactyly
      and to show the location of the bone shortening, as well as any associated
      malformation. This article reviews the radiological findings for isolated
      brachydactylies (according to the types classified by Bell, and Temtamy and
      McKusick) and for brachydactylies that are part of complex multisystem
      malformation syndromes. If warranted by the clinical and radiological
      examinations, a genetic analysis (molecular and/or cytogenetic) can confirm the
      etiologic diagnosis. 

PMID- 25758757
TI  - Force feeding at Guantanamo in first case brought to US federal court.

PMID- 25758758
TI  - Tough Beginnings on Galapagos, Baby Blue Footed Booby.

PMID- 25758759
TI  - Rebound coagulopathy in patients with snakebite presenting with marked initial
      coagulopathy.
AB  - OBJECTIVE: An estimated 70% of patients with pit viper snakebites require
      antivenom to treat serious complications such as coagulopathy. Evidence-based
      guidance is limited for the appropriate administration of Crotalinae Polyvalent
      Immune Fab (FabAV) and the duration of laboratory follow-up. The objective of our
      study was to assess the incidence of marked and recurrent envenomation
      coagulopathy at our trauma center and identify practice patterns that may prevent
      serious complications. METHODS: A retrospective case review was conducted over a
      3-year period on patients treated for symptomatic snakebite injury. Case records
      were reviewed for the inclusion criteria of international normalized ratio (INR)
      greater than 2.0. The exclusion criterion was limited to patients receiving
      anticoagulant therapy. RESULTS: In all, 61 patients were identified on
      retrospective chart review and 3 patients (4.9%) met inclusion criteria. Two of
      the 3 patients had marked rebound coagulopathy requiring readmission and
      additional treatment. In our small series, 2 patients presenting after crotaline
      envenomation with increased INR (>6.0), decreased fibrinogen (<60 mg/dL), and
      decreased platelet count (<100,000/mL) had recurrent coagulopathy and were
      asymptomatic, and recurrence was noted only with follow-up laboratory testing.
      All patients responded positively within a matter of hours to repeat FabAV
      administration, with resolution of rebound coagulopathy. CONCLUSIONS: We
      recommend periodic monitoring of patients with increased INR, decreased
      fibrinogen, and decreased platelet count. Patients should be monitored for 10 to
      14 days after envenomation to identify asymptomatic rebound coagulopathy. Prompt
      readministration of FabAV appears to correct the coagulopathy.

PMID- 25758761
TI  - Accuracy of staging laparoscopy in detecting peritoneal dissemination in patients
      with gastroesophageal adenocarcinoma.
AB  - Despite staging laparoscopy (SL) with peritoneal lavage is recommended in US
      Guidelines in patients with potentially resectable gastroesophageal
      adenocarcinoma, this procedure is not systematically proposed in French
      Guidelines. Therefore, we decided to analyze the results of systematic SL in
      patients considered for preoperative chemotherapy. From 2005 to 2011, 116
      consecutive patients with distal esophagus, esogastric junction, and gastric
      adenocarcinoma >=T3 or N+ without detectable metastatic dissemination by computed
      tomography (CT) scan imaging underwent SL before neoadjuvant chemotherapy.
      Positive and negative SLs were compared according to tumor characteristics. SL
      was positive in 15 cases (12.9%) including 14 with peritoneal seeding (localized
      in five, diffuse in nine). SL was positive in 7 (24.1%) of 29 patients with
      poorly differentiated tumor, in 9 (32.1%) of 28 patients with signet ring cells,
      in 7 (50%) of 14 patients with gastric linitis tumor, and in 15 (16.3%) of 92
      patients with T3 or T4 tumor. All the lesions of distal esophagus extending to
      the cardia had a negative SL. Among the 14 patients with peritoneal
      carcinomatosis at SL, nine (65%) had signs of peritoneal seeding on initial CT
      scan. One (0.8%) patient had a small bowel perforation closed laparoscopically.
      If systematic SL before preoperative chemotherapy does not seem justified because
      of its low accuracy, it should be performed in patients with poorly
      differentiated tumor, signet ring cell, and gastric linitis plastica components
      on biopsy and when CT scan is suggestive of T4 tumor, ascites, or peritoneal
      nodule. 

PMID- 25758762
TI  - Smoking and survival of colorectal cancer patients: population-based study from
      Germany.
AB  - Current evidence on the association between smoking and colorectal cancer (CRC)
      prognosis after diagnosis is heterogeneous and few have investigated dose
      response effects or outcomes other than overall survival. Therefore, the
      association of smoking status and intensity with several prognostic outcomes was
      evaluated in a large population-based cohort of CRC patients; 3,130 patients with
      incident CRC, diagnosed between 2003 and 2010, were interviewed on
      sociodemographic factors, smoking behavior, medication and comorbidities. Tumor
      characteristics were collected from medical records. Vital status, recurrence and
      cause of death were documented for a median follow-up time of 4.9 years. Using
      Cox proportional hazards regression, associations between smoking characteristics
      and overall, CRC-specific, non-CRC related, recurrence-free and disease-free
      survival were evaluated. Among stage I-III patients, being a smoker at diagnosis
      and smoking >=15 cigarettes/day were associated with lower recurrence-free
      (adjusted hazard ratios (aHR): 1.29; 95% confidence interval (CI): 0.93-1.79 and
      aHR: 1.31; 95%-CI: 0.92-1.87) and disease-free survival (aHR: 1.26; 95%-CI: 0.95
      1.67 and aHR: 1.29; 95%-CI: 0.94-1.77). Smoking was associated with decreased
      survival in stage I-III smokers with pack years >=20 (Overall survival: aHR:
      1.40; 95%-CI: 1.01-1.95), in colon cancer cases (Overall survival: aHR: 1.51; 95%
      CI: 1.05-2.17) and men (Recurrence-free survival: aHR: 1.51; 95%-CI: 1.09-2.10;
      disease-free survival: aHR: 1.49; 95%-CI: 1.12-1.97), whereas no associations
      were seen among women, stage IV or rectal cancer patients. The observed patterns
      support the existence of adverse effects of smoking on CRC prognosis among
      nonmetastatic CRC patients. The potential to enhance prognosis of CRC patients by
      promotion of smoking cessation, embedded in tertiary prevention programs warrants
      careful evaluation in future investigations. 

PMID- 25758763
TI  - Effective use of high CO2 efflux at the soil surface in a tropical understory
      plant.
AB  - Many terrestrial plants are C3 plants that evolved in the Mesozoic Era when
      atmospheric CO2 concentrations ([CO2]) were high. Given current conditions, C3
      plants can no longer benefit from high ambient [CO2]. Kaempferia marginata Carey
      is a unique understory ginger plant in the tropical dry forests of Thailand. The
      plant has two large flat leaves that spread on the soil surface. We found a large
      difference in [CO2] between the partly closed space between the soil surface and
      the leaves (638 umol mol(-1)) and the atmosphere at 20 cm above ground level (412
      umol mol(-1)). This finding indicates that the plants capture CO2 efflux from the
      soil. Almost all of the stomata are located on the abaxial leaf surface. When
      ambient air [CO2] was experimentally increased from 400 to 600 MUmol mol(-1), net
      photosynthetic rates increased by 45 to 48% under near light-saturated
      conditions. No significant increase was observed under low light conditions.
      These data demonstrate that the unique leaf structure enhances carbon gain by
      trapping soil CO2 efflux at stomatal sites under relatively high light
      conditions, suggesting that ambient air [CO2] can serve as an important selective
      agent for terrestrial C3 plants. 

PMID- 25758764
TI  - Cytokine-induced killer cells engineered with exogenous T-cell receptors directed
      against melanoma antigens: enhanced efficacy of effector cells endowed with a
      double mechanism of tumor recognition.
AB  - Cytokine-induced killer (CIK) cells consist of a heterogeneous population of
      polyclonal T lymphocytes displaying NK phenotype and HLA-unrestricted cytotoxic
      activity against a broad range of tumors. We sought to determine whether
      transduction of CIK cells with T cell receptor (TCR) genes specific for tumor
      associated antigens could generate effector cells endowed with a double mechanism
      of tumor recognition. HLA-A2-restricted TCR-transduced (TD) CIK directed against
      the melanoma antigens Mart1 and NY-ESO1 were generated by lentiviral transduction
      and successfully expanded over a 3-4-week period. TD-CIK cells were both
      CD3(+)/CD56(-) and CD3(+)/CD56(+) (31+/-8% and 59+/-9%, respectively), indicating
      that both major histocompatibility complex (MHC)-restricted T cells and MHC
      unrestricted CIK could be targeted by lentiviral transduction. At the end of the
      culture, the majority of both unmodified and TD-CIK displayed an effector memory
      phenotype, without considerable expression of replicative senescence and
      exhaustion markers. Functionally, TD-CIK specifically recognized tumor cells
      expressing the relevant antigen as well as maintained their MHC-unrestricted
      tumor activity. The cytotoxic activity of TD-CIK against HLA-A2(+) melanoma cell
      lines was significantly higher than the untransduced counterparts at a low
      effector:target ratio (cytotoxic activity of TD-CIK was from 1.9- to 4.3-fold
      higher than untransduced counterparts). TD-CIK were highly proficient in
      releasing high amount of IFN-gamma upon antigen-specific stimulation and were
      able to recognize primary melanoma targets. In conclusion, we showed that (1) the
      reproducibility and simplicity of CIK transduction and expansion might solve the
      problem of obtaining adequate numbers of potent antitumor effector cells for
      adoptive immunotherapy; (2) the presence of both terminal effectors as well as of
      less differentiated progenitors might confer them long survival in vivo; and (3)
      the addition of an MHC-restricted antigen recognition allows not only targeting
      tumor surface antigens but also a wider range of cytoplasmic or nuclear antigens,
      involved in tumor proliferation and survival. TD-CIK cells with a double
      mechanism of tumor recognition are an attractive and alternative tool for the
      development of efficient cell therapeutic strategies. 

PMID- 25758765
TI  - The beneficial effects of acute hypercapnia on microcirculatory oxygenation in an
      animal model of sepsis are independent of K(+)ATP channels.
AB  - BACKGROUND: Acute hypercapnia maintains the microcirculatory oxygenation of the
      splanchnic region during sepsis. The first aim of this study was to characterize
      the role of K(+)ATP channels on the microcirculatory flow and oxygenation during
      acute moderate hypercapnia. The second aim was to investigate whether a short
      period of hypercapnia induces detrimental effects in an otherwise undamaged
      rodent lung. METHODS: Experiments were performed on 60 male Wistar rats. A
      moderate polymicrobial sepsis was induced by colon ascendens stent peritonitis
      (CASP) surgery. 24h after induction of sepsis volume-controlled and pressure
      limited ventilation was established for 120 min, with either normocapnic (pCO2 35
      45 mmHg) or moderate hypercapnic ventilation targets (pCO2 65-75 mmHg) and with
      or without non-selective K(+)ATP channel blockade with glibenclamide.
      Microcirculatory blood flow of the colonic wall as well as oxygen delivery and
      consumption were assessed with tissue laser Doppler and reflectance
      spectrophotometry. Hemodynamic variables were recorded and plasma cytokine levels
      and myeloperoxidase levels of the lungs were analyzed. RESULTS: In septic animals
      microcirculatory oxygenation deteriorated progressively with normocapnia (-11.7
      +/- 11.8%) but was maintained (-2.9 +/- 5.6%) with hypercapnia. This effect was
      associated with an increased microcirculatory oxygen consumption in septic
      animals with normocapnia (+25.7 +/- 37.1%) that was decreased in the hypercapnia
      groups (-7.2 +/- 28.1%). The effect of hypercapnia in septic animals was not
      altered by additional K(+)ATP channel blockade (-5.7 +/- 32.7%). Hypercapnia
      neither induced an inflammatory response in lungs nor altered the systemic
      cytokine response. CONCLUSIONS: The observed beneficial effect of hypercapnia on
      microvascular oxygenation of the colon in sepsis does not seem to be mediated via
      K(+)ATP channels.

PMID- 25758766
TI  - Were Fertile Crescent crop progenitors higher yielding than other wild species
      that were never domesticated?
AB  - During the origin of agriculture in the Fertile Crescent, the broad spectrum of
      wild plant species exploited by hunter-gatherers narrowed dramatically. The
      mechanisms responsible for this specialization and the associated domestication
      of plants are intensely debated. We investigated why some species were
      domesticated rather than others, and which traits they shared. We tested whether
      the progenitors of cereal and pulse crops, grown individually, produced a higher
      yield and less chaff than other wild grasses and legumes, thereby maximizing the
      return per seed planted and minimizing processing time. We compared harvest
      traits of species originating from the Fertile Crescent, including those for
      which there is archaeological evidence of deliberate collection. Unexpectedly,
      wild crop progenitors in both families had neither higher grain yield nor, in
      grasses, less chaff, although they did have larger seeds. Moreover, small-seeded
      grasses actually returned a higher yield relative to the mass of seeds sown.
      However, cereal progenitors had threefold fewer seeds per plant, representing a
      major difference in how seeds are packaged on plants. These data suggest that
      there was no intrinsic yield advantage to adopting large-seeded progenitor
      species as crops. Explaining why Neolithic agriculture was founded on these
      species, therefore, remains an important unresolved challenge. 

PMID- 25758768
TI  - Effects of acute hypoglycemia on working memory and language processing in adults
      with and without type 1 diabetes.
AB  - OBJECTIVE: To examine the effects of hypoglycemia on language processing in
      adults with and without type 1 diabetes. RESEARCH DESIGN AND METHODS: Forty
      adults were studied (20 with type 1 diabetes and 20 healthy volunteers) using a
      hyperinsulinemic glucose clamp to lower blood glucose to 2.5 mmol/L (45 mg/dL)
      (hypoglycemia) for 60 min, or to maintain blood glucose at 4.5 mmol/L (81 mg/dL)
      (euglycemia), on separate occasions. Language tests were applied to assess the
      effects of hypoglycemia on the relationship between working memory and language
      (reading span), grammatical decoding (self-paced reading), and grammatical
      encoding (subject-verb agreement). RESULTS: Hypoglycemia caused a significant
      deterioration in reading span (P < 0.001; eta(2) = 0.37; Cohen d = 0.65) and a
      fall in correct responses (P = 0.005; eta(2) = 0.19; Cohen d = 0.41). On the self
      paced reading test, the reading time for the first sentence fragment increased
      during hypoglycemia (P = 0.039; eta(2) = 0.11; Cohen d = 0.25). For the reading
      of the next fragment, hypoglycemia affected the healthy volunteer group more than
      the adults with type 1 diabetes (P = 0.03; eta(2) = 0.12; Cohen d = 0.25).
      However, hypoglycemia did not significantly affect the number of errors in
      sentence comprehension or the time taken to answer questions. Hypoglycemia caused
      a deterioration of subject-verb agreement (correct responses: P = 0.011; eta(2) =
      0.159; Cohen d = 0.31). CONCLUSIONS: Hypoglycemia caused a significant
      deterioration in reading span and in the accuracy of subject-verb agreement, both
      of which are practical aspects of language involved in its everyday use. Language
      processing is therefore impaired during moderate hypoglycemia.

PMID- 25758767
TI  - Defects in calcium homeostasis and mitochondria can be reversed in Pompe disease.
AB  - Mitochondria-induced oxidative stress and flawed autophagy are common features of
      neurodegenerative and lysosomal storage diseases (LSDs). Although defective
      autophagy is particularly prominent in Pompe disease, mitochondrial function has
      escaped examination in this typical LSD. We have found multiple mitochondrial
      defects in mouse and human models of Pompe disease, a life-threatening cardiac
      and skeletal muscle myopathy: a profound dysregulation of Ca(2+) homeostasis,
      mitochondrial Ca(2+) overload, an increase in reactive oxygen species, a decrease
      in mitochondrial membrane potential, an increase in caspase-independent
      apoptosis, as well as a decreased oxygen consumption and ATP production of
      mitochondria. In addition, gene expression studies revealed a striking
      upregulation of the beta 1 subunit of L-type Ca(2+) channel in Pompe muscle
      cells. This study provides strong evidence that disturbance of Ca(2+) homeostasis
      and mitochondrial abnormalities in Pompe disease represent early changes in a
      complex pathogenetic cascade leading from a deficiency of a single lysosomal
      enzyme to severe and hard-to-treat autophagic myopathy. Remarkably, L-type
      Ca(2+)channel blockers, commonly used to treat other maladies, reversed these
      defects, indicating that a similar approach can be beneficial to the plethora of
      lysosomal and neurodegenerative disorders. 

PMID- 25758769
TI  - Efficacy and safety of saxagliptin in older participants in the SAVOR-TIMI 53
      trial.
AB  - OBJECTIVE: To examine the safety and cardiovascular (CV) effects of saxagliptin
      in the predefined elderly (>=65 years) and very elderly (>=75 years)
      subpopulations of the Saxagliptin Assessment of Vascular Outcomes Recorded in
      Patients with Diabetes Mellitus-Thrombolysis in Myocardial Infarction 53 (SAVOR
      TIMI 53) trial. RESEARCH DESIGN AND METHODS: Individuals >=40 years (n = 16,492;
      elderly, n = 8,561; very elderly, n = 2,330) with HbA1c >=6.5% (47.5 mmol/mol)
      and <=12.0% (107.7 mmol/mol) were randomized (1:1) to saxagliptin (5 or 2.5 mg
      daily) or placebo in a double-blind trial for a median follow-up of 2.1 years.
      RESULTS: The hazard ratio (HR) for the comparison of saxagliptin versus placebo
      for the primary end point (composite of CV mortality, myocardial infarction, or
      ischemic stroke) was 0.92 for elderly patients vs. 1.15 for patients <65 years (P
      = 0.06) and 0.95 for very elderly patients. The HRs for the secondary composite
      end points in the entire cohort, elderly cohort, and very elderly cohort were
      similar. Although saxagliptin increased the risk of hospitalization for heart
      failure in the overall saxagliptin population, there was no age-based treatment
      interaction (P = 0.76 for elderly patients vs. those <65 years; P = 0.34 for very
      elderly patients vs. those <75 years). Among saxagliptin-treated individuals with
      baseline HbA1c >=7.6% (59.6 mmol/mol), the mean change from baseline HbA1c at 2
      years was -0.69%, -0.64%, -0.66%, and -0.66% for those >=65, <65, >=75, and <75
      years old, respectively. The incidence of overall adverse events (AEs) and
      serious AEs was similar between saxagliptin and placebo in all cohorts; however,
      hypoglycemic events were higher for saxagliptin versus placebo regardless of age.
      CONCLUSIONS: The SAVOR-TIMI 53 trial supports the overall CV safety of
      saxagliptin in a robust number of elderly and very elderly participants, although
      the risk of heart failure hospitalization was increased irrespective of age
      category. AEs and serious AEs as well as glycemic efficacy of saxagliptin in
      elderly patients are similar to those found in younger patients.

PMID- 25758771
TI  - Serum mannose-binding lectin is a strong biomarker of diabetic retinopathy in
      chinese patients with diabetes.
AB  - OBJECTIVE: Inflammation and complement activation initiated by mannose-binding
      lectin (MBL) may be implicated in the pathogenesis of diabetic vascular
      complications. We investigated serum MBL levels in patients with diabetes with
      and without diabetic retinopathy (DR). RESEARCH DESIGN AND METHODS: Serum MBL
      levels were determined in 348 patients with diabetes and in 100 healthy control
      subjects. The prediction value of MBL was compared with diabetes duration, hs
      CRP, and other known predictors. Multivariate analyses were performed using
      logistic regression models. RESULTS: MBL levels on admission were significantly
      increased in patients with diabetes with DR (P < 0.0001) and vision-threatening
      DR (VTDR; P < 0.0001). Multivariate logistic regression analysis adjusted for
      common indictors showed that serum MBL levels >=3,385 MUg/L were an independent
      predictor of DR (odds ratio [OR] 3.14, 95% CI 1.77-5.57) and VTDR (OR 7.83, 95%
      CI 3.35-18.31). The area under the receiver operating characteristic curve of MBL
      was 0.81 (95% CI 0.76-0.86) for DR and 0.84 (95% CI 0.74-0.93) for VTDR.
      CONCLUSIONS: The current study demonstrated that MBL appears to be an independent
      biomarker for DR in the Chinese population, suggesting a possible role of MBL in
      the pathogenesis of DR complications in diabetes.

PMID- 25758772
TI  - Analysis of the genetic diversity of influenza A viruses using next-generation
      DNA sequencing.
AB  - BACKGROUND: Influenza viruses exist as a large group of closely related viral
      genomes, also called quasispecies. The composition of this influenza viral
      quasispecies can be determined by an accurate and sensitive sequencing technique
      and data analysis pipeline. We compared the suitability of two benchtop next
      generation sequencers for whole genome influenza A quasispecies analysis: the
      Illumina MiSeq sequencing-by-synthesis and the Ion Torrent PGM semiconductor
      sequencing technique. RESULTS: We first compared the accuracy and sensitivity of
      both sequencers using plasmid DNA and different ratios of wild type and mutant
      plasmid. Illumina MiSeq sequencing reads were one and a half times more accurate
      than those of the Ion Torrent PGM. The majority of sequencing errors were
      substitutions on the Illumina MiSeq and insertions and deletions, mostly in
      homopolymer regions, on the Ion Torrent PGM. To evaluate the suitability of the
      two techniques for determining the genome diversity of influenza A virus, we
      generated plasmid-derived PR8 virus and grew this virus in vitro. We also
      optimized an RT-PCR protocol to obtain uniform coverage of all eight genomic RNA
      segments. The sequencing reads obtained with both sequencers could successfully
      be assembled de novo into the segmented influenza virus genome. After mapping of
      the reads to the reference genome, we found that the detection limit for reliable
      recognition of variants in the viral genome required a frequency of 0.5% or
      higher. This threshold exceeds the background error rate resulting from the RT
      PCR reaction and the sequencing method. Most of the variants in the PR8 virus
      genome were present in hemagglutinin, and these mutations were detected by both
      sequencers. CONCLUSIONS: Our approach underlines the power and limitations of two
      commonly used next-generation sequencers for the analysis of influenza virus gene
      diversity. We conclude that the Illumina MiSeq platform is better suited for
      detecting variant sequences whereas the Ion Torrent PGM platform has a shorter
      turnaround time. The data analysis pipeline that we propose here will also help
      to standardize variant calling in small RNA genomes based on next-generation
      sequencing data.

PMID- 25758773
TI  - Dying myofibers in elderly mouse skeletal muscles are characterized by the
      appearance of dystrophin-encircled vacuoles.
AB  - The age-related loss of skeletal muscle mass and strength (sarcopenia) is
      predominantly attributed to myofiber atrophy, however the role or existence of
      myofiber death is currently unclear. We recently discovered dysmorphic myofibers
      in normal elderly mice resembling those that characterize the Autophagic Vacuolar
      Myopathies, and speculated that they may be myofibers caught in the act of dying.
      Since these myofibers were identifiable by Dystrophin Encircled Vacuoles and
      invaginations with Intracellular Localization we coined the acronym DEVILs and
      aimed to determine their frequency, pathogenesis and correlation with myofiber
      loss. In whole transverse sections of young (1-6 month) and elderly (22-26 month)
      C57Bl/6j mouse muscles, DEVILated myofiber number correlated with myofiber loss,
      being increasingly prevalent in aged extensor digitorum longus (R = 0.7, p <
      0.001) and soleus (R = 0.6, p = 0.004) muscles, whilst rare in myofiber loss
      resistant muscles (cleido- and sternomastoid). In a cell viability dye-exclusion
      test, 17 +/- 14% of DEVILated myofibers stained positive and were accompanied by
      immunoglobulin infiltration compared to 1 +/- 1% of normal myofibers (p = 0.029).
      Virtually all DEVILs were acid-phosphatase reactive but contained p62
      immunoreactivity and periodic acid-Schiff stained plaques. Compared to normal
      myofibers, BNIP3 immunostaining in DEVILated myofibers was reduced, whilst MAP
      LC3b was indifferent. Cleaved-caspase 3 immunoreactivity was marginally elevated
      in DEVILated myofibers, but unaccompanied by nuclear DNA fragmentation. DEVILated
      myofibers were also identified in elderly rat (24 month) and cadaveric human (78
      years) muscles. We argue that DEVIL formation reflects a previously undescribed
      fibre death process via a mechanism involving autophagic dysfunction and that the
      process may represent our first direct insight into the mechanism by which
      myofibers are lost in old age.

PMID- 25758774
TI  - Methanol extracts from the resurrection plant Haberlea rhodopensis ameliorate
      cellular vitality in chronologically ageing Saccharomyces cerevisiae cells.
AB  - Bioactive substances that are found in many natural plant extracts are very
      important for the cosmetics, pharmaceutical industry and biotechnology.
      Especially interesting for these industries are the substances that possess cell
      revitalizing and anti-ageing properties. The endemic plant Haberlea rhodopensis
      is known for its ability to withstand drought and to revitalize when returned to
      optimal conditions after a long time in desiccation. It is a mere fact that this
      plant not only can completely resurrect from a dried state but is also able to
      bring back the natural biochemical compositions of its cells. As a result H.
      rhodopensis offers a wide field for investigation of the exact mechanisms of the
      revitalization process as well as broadens the search for unique bioactive
      chemical substances in its cells. Here, by using the yeast Saccharomyces
      cerevisiae as a model we have demonstrated that methanol extracts from the plant
      H. rhodopensis hold specific properties to revitalize and ameliorate cellular
      growth as well as to balance intracellular metabolic states. Our results add
      valuable knowledge on the effects of natural compounds on ageing and reinforce
      the idea of using yeast as a model organism in the development of rapid tests for
      studying the efficacy of different bioactive substances. 

PMID- 25758775
TI  - All-optical, polarization-insensitive light tuning properties in silver nanorod
      arrays covered with photoresponsive liquid crystals.
AB  - Active plasmonics has been an interesting and important topic recently. Here we
      demonstrate the all-optical, polarization-insensitive tunable manipulation of a
      hybrid system that integrates a silver nanorod array with photoresponsive liquid
      crystals. The large-area plasmonic nanorod arrays are fabricated by laser
      interference lithography and ion milling. By covering a layer of photoresponsive
      liquid crystals, tunable control of plasmon resonance is achieved under an
      external light pump. The silver nanorod array also enables the homeotropic
      alignment of the liquid crystals, which makes the all-optical tuning behavior
      polarization-insensitive. With its advantages of cost-effective fabrication, easy
      integration, all-optical control, and polarization-insensitivity, the hybrid
      system could be valuable in many nanophotonic applications. 

PMID- 25758776
TI  - Deep cutaneous infection with Microsphaeropsis arundinis: report of two Japanese
      cases.

PMID- 25758777
TI  - Acetylcholinesterase Inhibition Attenuates the Development of Hypertension and
      Inflammation in Spontaneously Hypertensive Rats.
AB  - BACKGROUND: It is hypothesized that chronic increase of availability of
      acetylcholine, resulting from the effect of antiacetylcholinesterases, may
      prevent autonomic imbalance and reduce inflammation yielding benefic effects for
      cardiovascular disorders in hypertension. The effect of long-term administration
      of antiacetylcholinesterase agents with central and/or peripheral action, i.e.,
      donepezil and pyridostigmine, were investigated on arterial pressure (AP),
      sympathovagal balance, plasma cytokine levels, and cardiac remodeling in
      spontaneously hypertensive rats (SHR). METHODS: Chronic treatment with donepezil
      or pyridostigmine started before the onset of hypertension. AP was measured by
      plethysmography every 4 weeks. At the end of 16 weeks of treatment,
      methylatropine was used to evaluate the cardiac vagal tone; AP and pulse interval
      (PI) variability were also evaluated followed by plasma and heart collection for
      analysis. RESULTS: Pyridostigmine, which does not cross the blood-brain barrier,
      increased cardiac vagal tone, and reduced cardiomyocyte diameter and collagen
      density, but did not affect the AP and plasma cytokine levels. Donepezil, which
      crosses the blood-brain barrier, attenuated the development of hypertension,
      increased cardiac vagal tone, and improved AP and PI variability. Likewise,
      donepezil reduced the plasma levels of tumor necrosis factor-alpha, interleukin
      6, and interferon gamma, besides reducing cardiomyocyte diameter and collagen
      density. CONCLUSIONS: Donepezil attenuated the development of hypertension in SHR
      probably involving antiinflammatory effects, indicating that acetylcholinesterase
      inhibition yields benefic effects for antihypertensive therapy.

PMID- 25758778
TI  - Vaspin: a new adipokine correlating the levels of crevicular fluid and tear fluid
      in periodontitis and obesity.
AB  - AIM: In the present study, we investigated the levels of vaspin in gingival
      crevicular fluid (GCF) and tear fluid in obese patients with chronic
      periodontitis (CP), and sought to find an association, if any. METHODS: Forty
      patients (20 males and 20 females) with moderate-severe CP were selected based on
      their clinical parameters of gingival index, probing depth (PD), clinical
      attachment level (CAL), bleeding on probing, body mass index (BMI), and waist
      circumference, and divided into four groups (n = 10/group): group 1 (healthy non
      obese), group 2 (healthy obese), group 3 (non-obese with CP), and group 4 (obese
      with CP). GCF and tear fluid vaspin levels were estimated by enzyme-linked
      immunosorbent assay. RESULTS: The mean vaspin concentration both in GCF and tear
      fluid was greater for group 4 (1.84 +/- 0.03) and (1.98 +/- 0.08), followed by
      groups 3 (1.35 +/- 0.03 and 1.50 +/- 0.06), 2 (0.95 +/- 0.26 and 1.27 +/- 0.51),
      and then 1 (0.65 +/- 0.02 and 0.75 +/- 0.02), respectively. Mean vaspin levels
      correlated with BMI, CAL, and PD. The association between GCF and tear fluid
      vaspin concentration was also statistically significant (P < 0.001). CONCLUSION:
      Vaspin can be a novel biomarker connecting inflammatory marker for the systemic
      inflammatory response in obesity and CP.

PMID- 25758779
TI  - A peculiar molecular profile of umbilical cord-mesenchymal stromal cells drives
      their inhibitory effects on multiple myeloma cell growth and tumor progression.
AB  - Bone marrow-derived mesenchymal stromal cells (BM-MSCs) are under intensive
      investigation in preclinical models of cytotherapies against cancer, including
      multiple myeloma (MM). However, the therapeutic use of stromal progenitors holds
      critical safety concerns due to their potential MM-supporting activity in vivo.
      Here, we explored whether MSCs from sources other than BM, such as adipose tissue
      (AD-MSCs) and umbilical cord (UC-MSCs), affect MM cell growth in comparison to
      either normal (nBM-MSCs) or myelomatous marrow MSCs (MM-BM-MSCs). Results from
      both proliferation and clonogenic assays indicated that, in contrast to nBM- and
      MM-BM-MSCs, both AD and particularly UC-MSCs significantly inhibit MM cell
      clonogenicity and growth in vitro. Furthermore, when co-injected with UC-MSCs
      into mice, RPMI-8226 MM cells formed smaller subcutaneous tumor masses, while
      peritumoral injections of the same MSC subtype significantly delayed the tumor
      burden growing in subcutaneous plasmocytoma-bearing mice. Finally, both
      microarrays and ELISA revealed different expression of several genes and soluble
      factors in UC-MSCs as compared with other MSCs. Our data suggest that UC-MSCs
      have a distinct molecular profile that correlates with their intrinsic anti-MM
      activity and emphasize the UCs as ideal sources of MSCs for future cell-based
      therapies against MM. 

PMID- 25758780
TI  - Genetic evidence that both dNTP-stabilized and strand slippage mechanisms may
      dictate DNA polymerase errors within mononucleotide microsatellites.
AB  - Mononucleotide microsatellites are tandem repeats of a single base pair, abundant
      within coding exons and frequent sites of mutation in the human genome. Because
      the repeated unit is one base pair, multiple mechanisms of insertion/deletion
      (indel) mutagenesis are possible, including strand-slippage, dNTP-stabilized, and
      misincorportion-misalignment. Here, we examine the effects of polymerase identity
      (mammalian Pols alpha, beta, kappa, and eta), template sequence, dNTP pool size,
      and reaction temperature on indel errors during in vitro synthesis of
      mononucleotide microsatellites. We utilized the ratio of insertion to deletion
      errors as a genetic indicator of mechanism. Strikingly, we observed a
      statistically significant bias toward deletion errors within mononucleotide
      repeats for the majority of the 28 DNA template and polymerase combinations
      examined, with notable exceptions based on sequence and polymerase identity.
      Using mutator forms of Pol beta did not substantially alter the error
      specificity, suggesting that mispairing-misalignment mechanism is not a primary
      mechanism. Based on our results for mammalian DNA polymerases representing three
      structurally distinct families, we suggest that dNTP-stabilized mutagenesis may
      be an alternative mechanism for mononucleotide microsatellite indel mutation. The
      change from a predominantly dNTP-stabilized mechanism to a strand-slippage
      mechanism with increasing microsatellite length may account for the differential
      rates of tandem repeat mutation that are observed genome-wide.

PMID- 25758781
TI  - Alterations of DNA repair genes in the NCI-60 cell lines and their predictive
      value for anticancer drug activity.
AB  - Loss of function of DNA repair (DNAR) genes is associated with genomic
      instability and cancer predisposition; it also makes cancer cells reliant on a
      reduced set of DNAR pathways to resist DNA-targeted therapy, which remains the
      core of the anticancer armamentarium. Because the landscape of DNAR defects
      across numerous types of cancers and its relation with drug activity have not
      been systematically examined, we took advantage of the unique drug and genomic
      databases of the US National Cancer Institute cancer cell lines (the NCI-60) to
      characterize 260 DNAR genes with respect to deleterious mutations and expression
      down-regulation; 169 genes exhibited a total of 549 function-affecting
      alterations, with 39 of them scoring as putative knockouts across 31 cell lines.
      Those mutations were compared to tumor samples from 12 studies of The Cancer
      Genome Atlas (TCGA) and The Cancer Cell Line Encyclopedia (CCLE). Based on this
      compendium of alterations, we determined which DNAR genomic alterations predicted
      drug response for 20,195 compounds present in the NCI-60 drug database. Among 242
      DNA damaging agents, 202 showed associations with at least one DNAR genomic
      signature. In addition to SLFN11, the Fanconi anemia-scaffolding gene SLX4
      (FANCP/BTBD12) stood out among the genes most significantly related with DNA
      synthesis and topoisomerase inhibitors. Depletion and complementation experiments
      validated the causal relationship between SLX4 defects and sensitivity to
      raltitrexed and cytarabine in addition to camptothecin. Therefore, we propose new
      rational uses for existing anticancer drugs based on a comprehensive analysis of
      DNAR genomic parameters. 

PMID- 25758782
TI  - Fidelity consequences of the impaired interaction between DNA polymerase epsilon
      and the GINS complex.
AB  - DNA polymerase epsilon interacts with the CMG (Cdc45-MCM-GINS) complex by Dpb2p,
      the non-catalytic subunit of DNA polymerase epsilon. It is postulated that CMG is
      responsible for targeting of Pol E to the leading strand. We isolated a mutator
      dpb2-100 allele which encodes the mutant form of Dpb2p. We showed previously that
      Dpb2-100p has impaired interactions with Pol2p, the catalytic subunit of Pol E.
      Here, we present that Dpb2-100p has strongly impaired interaction with the Psf1
      and Psf3 subunits of the GINS complex. Our in vitro results suggest that while
      dpb2-100 does not alter Pol E's biochemical properties including catalytic
      efficiency, processivity or proofreading activity - it moderately decreases the
      fidelity of DNA synthesis. As the in vitro results did not explain the strong in
      vivo mutator effect of the dpb2-100 allele we analyzed the mutation spectrum in
      vivo. The analysis of the mutation rates in the dpb2-100 mutant indicated an
      increased participation of the error-prone DNA polymerase zeta in replication.
      However, even in the absence of Pol zeta activity the presence of the dpb2-100
      allele was mutagenic, indicating that a significant part of mutagenesis is Pol
      zeta-independent. A strong synergistic mutator effect observed for transversions
      in the triple mutant dpb2-100 pol2-4 rev3Delta as compared to pol2-4 rev3Delta
      and dpb2-100 rev3Delta suggests that in the presence of the dpb2-100 allele the
      number of replication errors is enhanced. We hypothesize that in the dpb2-100
      strain, where the interaction between Pol E and GINS is weakened, the access of
      Pol delta to the leading strand may be increased. The increased participation of
      Pol delta on the leading strand in the dpb2-100 mutant may explain the
      synergistic mutator effect observed in the dpb2-100 pol3-5DV double mutant. 

PMID- 25758783
TI  - The role of preformed silos in the management of infants with gastroschisis: a
      systematic review and meta-analysis.
AB  - BACKGROUND: The pre-formed silo (PFS) is increasingly used in the management of
      gastroschisis, but its benefits remain unclear. We performed a systematic review
      and meta-analysis of the literature comparing use of a PFS with alternate
      treatment strategies. METHODS: Studies comparing the use of a PFS with alternate
      strategies were identified and data extracted. The primary outcome measure was
      length of time on a ventilator. Mean difference (MD) between continuous variables
      and 95% confidence intervals were calculated. Risk difference and 95% CI were
      determined for dichotomous data. RESULTS: Eighteen studies, including one
      randomised controlled trial, were included. Treatment strategy and outcome
      measures reported varied widely. Meta-analysis demonstrated no difference in days
      of ventilation, but a longer duration of parenteral nutrition (PN) requirement
      [MD 6.4 days (1.3, 11.5); p = 0.01] in infants who received a PFS. Subgroup
      analysis of studies reporting routine use of a PFS for all infants demonstrated a
      significantly shorter duration of ventilation with a PFS [MD 2.2 days (0.5, 3.9);
      p = 0.01] but no difference in duration of PN requirement. Other outcomes were
      similar between groups. CONCLUSION: The quality of evidence comparing PFS with
      alternate treatment strategies for gastroschisis is poor. Only routine use of PFS
      is associated with fewer days on a ventilator compared with other strategies. No
      strong evidence to support a preference for any strategy was demonstrated.
      Prospective studies are required to investigate the optimum management of
      gastroschisis. Standardised outcome measures for this population should be
      established to allow comparison of studies.

PMID- 25758785
TI  - Watch out! Directional threat-related postures cue attention and the eyes.
AB  - Previous work indicates that threatening facial expressions with averted eye gaze
      can act as a signal of imminent danger, enhancing attentional orienting in the
      gazed-at direction. However, this threat-related gaze-cueing effect is only
      present in individuals reporting high levels of anxiety. The present study used
      eye tracking to investigate whether additional directional social cues, such as
      averted angry and fearful human body postures, not only cue attention, but also
      the eyes. The data show that although body direction did not predict target
      location, anxious individuals made faster eye movements when fearful or angry
      postures were facing towards (congruent condition) rather than away (incongruent
      condition) from peripheral targets. Our results provide evidence for attentional
      cueing in response to threat-related directional body postures in those with
      anxiety. This suggests that for such individuals, attention is guided by
      threatening social stimuli in ways that can influence and bias eye movement
      behaviour. 

PMID- 25758786
TI  - The Behaviour Problems Inventory-Short Form: Reliability and Factorial Validity
      in Adults with Intellectual Disabilities.
AB  - BACKGROUND: The Behaviour Problems Inventory-Short Form (BPI-S) is a spin-off of
      the BPI-01 that was empirically developed from a large BPI-01 data set. In this
      study, the reliability and factorial validity of the BPI-S was investigated for
      the first time on newly collected data from adults with intellectual
      disabilities. METHODS: The sample consisted of 232 adults with intellectual
      disabilities who represented all levels of intellectual functioning. They were
      recruited at several day programs in the USA (n = 148) and the UK (n = 84).
      RESULTS: We found acceptable reliability in terms of internal consistency, inter
      rater agreement and test-retest reliability. Confirmatory factor analysis
      validated the three BPI-S subscale structure. CONCLUSIONS: We corroborated the
      factor structure underly-ing the three subscales and found the BPI-S to have
      adequate to good psychometric properties in a newly collected sample of adults
      with intellectual disabilities.

PMID- 25758784
TI  - Immunotoxin targeting glypican-3 regresses liver cancer via dual inhibition of
      Wnt signalling and protein synthesis.
AB  - Glypican-3 is a cell surface glycoprotein that associates with Wnt in liver
      cancer. We develop two antibodies targeting glypican-3, HN3 and YP7. The first
      antibody recognizes a functional epitope and inhibits Wnt signalling, whereas the
      second antibody recognizes a C-terminal epitope but does not inhibit Wnt
      signalling. Both are fused to a fragment of Pseudomonas exotoxin A (PE38) to
      create immunotoxins. Interestingly, the immunotoxin based on HN3 (HN3-PE38) has
      superior antitumor activity as compared with YP7 (YP7-PE38) both in vitro and in
      vivo. Intravenous administration of HN3-PE38 alone, or in combination with
      chemotherapy, induces regression of Hep3B and HepG2 liver tumour xenografts in
      mice. This study establishes glypican-3 as a promising candidate for immunotoxin
      based liver cancer therapy. Our results demonstrate immunotoxin-induced tumour
      regression via dual mechanisms: inactivation of cancer signalling via the
      antibody and inhibition of protein synthesis via the toxin. 

PMID- 25758787
TI  - Evolutionary perspectives on learning: conceptual and methodological issues in
      the study of adaptive specializations.
AB  - Inquiry into evolutionary adaptations has flourished since the modern synthesis
      of evolutionary biology. Comparative methods, genetic techniques, and various
      experimental and modeling approaches are used to test adaptive hypotheses. In
      psychology, the concept of adaptation is broadly applied and is central to
      comparative psychology and cognition. The concept of an adaptive specialization
      of learning is a proposed account for exceptions to general learning processes,
      as seen in studies of Pavlovian conditioning of taste aversions, sexual
      responses, and fear. The evidence generally consists of selective associations
      forming between biologically relevant conditioned and unconditioned stimuli, with
      conditioned responses differing in magnitude, persistence, or other measures
      relative to non-biologically relevant stimuli. Selective associations for
      biologically relevant stimuli may suggest adaptive specializations of learning,
      but do not necessarily confirm adaptive hypotheses as conceived of in
      evolutionary biology. Exceptions to general learning processes do not necessarily
      default to an adaptive specialization explanation, even if experimental results
      "make biological sense". This paper examines the degree to which hypotheses of
      adaptive specializations of learning in sexual and fear response systems have
      been tested using methodologies developed in evolutionary biology (e.g.,
      comparative methods, quantitative and molecular genetics, survival experiments).
      A broader aim is to offer perspectives from evolutionary biology for testing
      adaptive hypotheses in psychological science. 

PMID- 25758788
TI  - Individual and regional factors of access to the renal transplant waiting list in
      france in a cohort of dialyzed patients.
AB  - Several studies have investigated geographical variations in access to renal
      transplant waiting lists, but none has assessed the impact on these variations of
      factors at both the patient and geographic levels. The objective of our study was
      to identify medical and non-medical factors at both these levels associated with
      these geographical variations in waiting-list placement in France. We included
      all incident patients aged 18-80 years in 11 French regions who started dialysis
      between January 1, 2006, and December 31, 2008. Both a multilevel Cox model with
      shared frailty and a competing risks model were used for the analyses. At the
      patient level, old age, comorbidities, diabetic nephropathy, non-autonomous first
      dialysis, and female gender were the major determinants of a lower probability of
      being waitlisted. At the regional level, the only factor associated with this
      probability was an increase in the number of patients on the waiting list from
      2005 to 2009. This finding supports a slight but significant impact of a regional
      organ shortage on waitlisting practices. Our findings demonstrate that patients'
      age has a major impact on waitlisting practices, even for patients with no
      comorbidity or disability, whose survival would likely be improved by
      transplantation compared with dialysis. 

PMID- 25758789
TI  - Endothelial cells in health and disease.
AB  - According to the World Health Organization, from 2014, cardiovascular diseases
      (CVD) are the number one cause of death worldwide. One of the key players in
      maintaining proper cardiovascular function is the endothelium, the inner layer of
      all blood vessels. This monolayer of cells on one hand serves as a barrier
      between blood and the surrounding tissue and on the other hand regulates many
      aspects of vessel function. Therefore, it is not surprising that interventions
      reducing the risk for CVD improve endothelial function. There is a clear
      correlation between endothelial dysfunction, in which the endothelial homeostasis
      is disturbed, and the development and progression of many CVD. Thus, the
      development of diagnostic tools for early detection of disturbances in
      endothelial homeostasis or interventions aimed at improving endothelial function
      after insults require a comprehensive knowledge not only of the cellular
      reactions to the positive or negative stimuli but also of the molecular
      mechanisms relaying these responses. Thus, this Forum on "endothelial cells in
      health and disease" focuses on key molecules and processes intimately involved in
      endothelial cell function and covers areas from endothelial nitric oxide synthase
      dependent processes, over the group of Phox-Bem1 domain proteins, cytochrome P450
      epoxygenase-derived metabolites, and pre-mRNA splicing to microRNAs. Finally, one
      has to conclude that keeping endothelial homeostasis is the central key for a
      healthy long life of the human individual.

PMID- 25758790
TI  - The insulin and IGF1 receptor kinase domains are functional dimers in the
      activated state.
AB  - The insulin receptor (IR) and insulin-like growth factor-1 receptor (IGF1R) are
      highly related receptor tyrosine kinases with a disulfide-linked homodimeric
      architecture. Ligand binding to the receptor ectodomain triggers tyrosine
      autophosphorylation of the cytoplasmic domains, which stimulates catalytic
      activity and creates recruitment sites for downstream signalling proteins.
      Whether the two phosphorylated tyrosine kinase domains within the receptor dimer
      function independently or cooperatively to phosphorylate protein substrates is
      not known. Here we provide crystallographic, biophysical and biochemical evidence
      demonstrating that the phosphorylated kinase domains of IR and IGF1R form a
      specific dimeric arrangement involving an exchange of the juxtamembrane region
      proximal to the kinase domain. In this dimer, the active position of alpha-helix
      C in the kinase N lobe is stabilized, which promotes downstream substrate
      phosphorylation. These studies afford a novel strategy for the design of small
      molecule IR agonists as potential therapeutic agents for type 2 diabetes. 

PMID- 25758791
TI  - A monomer-trimer model supports intermittent glucagon fibril growth.
AB  - We investigate in vitro fibrillation kinetics of the hormone peptide glucagon at
      various concentrations using confocal microscopy and determine the glucagon
      fibril persistence length 60MUm. At all concentrations we observe that periods of
      individual fibril growth are interrupted by periods of stasis. The growth
      probability is large at high and low concentrations and is reduced for
      intermediate glucagon concentrations. To explain this behavior we propose a
      simple model, where fibrils come in two forms, one built entirely from glucagon
      monomers and one entirely from glucagon trimers. The opposite building blocks act
      as fibril growth blockers, and this generic model reproduces experimental
      behavior well. 

PMID- 25758794
TI  - OPTN and UNOS Update.

PMID- 25758793
TI  - Pacesetters and pathfinders: an interview with Barbara Schulman, RN.

PMID- 25758792
TI  - Analysis of carbonated thin liquids in pediatric neurogenic dysphagia.
AB  - BACKGROUND: Aspiration of liquids is a serious complication of neurological
      impairments such as traumatic brain injury or stroke. Carbonated liquids have
      been examined as a possible alternative to thickened liquids to help reduce
      aspiration in cases of dysphagia in adults, but no published literature to the
      best of our knowledge has evaluated this technique in children. If carbonated
      liquids result in safer swallowing in children, they could provide a preferred
      alternative to thickened liquids. OBJECTIVE: This pilot study examined whether
      carbonated thin liquids (CARB) improved swallowing compared to non-carbonated
      thin liquids (NOCARB) for children with neurogenic dysphagia. MATERIALS AND
      METHODS: Twenty-four children admitted to a level I trauma center for acute
      neurological injury/disease were evaluated via videofluoroscopic swallow studies.
      Four descriptive outcome measures were contrasted. RESULTS: CARB significantly
      decreased pooling (P = 0.0006), laryngeal penetration/aspiration (P = 0.0044) and
      Penetration-Aspiration Scale scores (P = 0.0127) when compared to NOCARB. On
      average, CARB improved scores on the Penetration-Aspiration Scale by 3.7 points
      for participants who aspirated NOCARB. There was no significant difference in
      pharyngeal residue noted between CARB and NOCARB (P = 0.0625). CONCLUSION: These
      findings support the hypothesis that carbonated thin liquids may provide an
      alternative to thickened liquids for children with neurogenic dysphagia.
      Implications for future research and clinical practice are discussed.

PMID- 25758795
TI  - Determinants of frequent Internet use in an urban kidney transplant population in
      the United States: characterizing the digital divide.
AB  - CONTEXT: The Internet is a staple of electronic communication and is essential to
      the emerging telemonitoring and health information technology interventions for
      adults with chronic diseases. OBJECTIVE: To identify determinants of frequent
      Internet use in an urban kidney transplant population in the United States.
      DESIGN: A single center, cross-sectional survey study. SETTING: An urban
      Midwestern transplant center. PARTICIPANTS: 78 pretransplant and 177
      posttransplant patients. MAIN OUTCOME MEASURES: Frequent Internet use, defined as
      using the Internet more than 5 hours per week. RESULTS: Only 38% of participants
      reported being frequent Internet users. Non-Hispanic blacks and participants who
      reported their race/ethnicity as "other" were significantly less likely than
      whites to report being frequent Internet users. Women were 59% less likely than
      men to be frequent users of the Internet. Those who reported having kidney
      disease for more than 3 years were more likely to report being frequent Internet
      users. As education increased, Internet use increased. As age increased, Internet
      use decreased. CONCLUSION: Alternatives to electronic information sources and/or
      additional resources should be considered for those who may fall in the so-called
      digital divide.

PMID- 25758796
TI  - Identifying the educational needs of lung transplant recipients with cystic
      fibrosis.
AB  - PURPOSE: To elucidate the education needs of patients who have undergone lung
      transplant for cystic fibrosis while participating in the development of
      therapeutic education programs in French transplant centers. METHODS: From
      January 2009 to March 2012, in-depth educational diagnosis interviews were
      conducted with 42 adult transplant recipients with cystic fibrosis who were being
      followed up at 7 French transplant centers. Several areas were explored: health
      status, social and occupational outcomes, knowledge about the disease and
      treatments, and experience of the disease. The interviews combined open- and
      closed-ended questions for more systematic exploration of knowledge about the
      disease and treatments. RESULTS: After receiving the transplant, the patients'
      health had improved and their lives were returning to normal. They had acquired
      much usable knowledge about managing their disease. Educational needs regarding
      transplant-related complications and management of immunosuppressive drugs were
      evident. The analysis also demonstrated the need to better inform patients about
      pregnancy and new social rights and to offer them psychological support in
      adjusting to their new health status. CONCLUSION: Therapeutic education of
      patients should continue well after transplant to maintain safety knowledge and
      meet patients' new needs. A comprehensive therapeutic education program for
      transplant candidates that includes the preparatory, immediate posttransplant,
      and late posttransplant phases is needed.

PMID- 25758797
TI  - Attitudes and perceptions of patients on the kidney transplant waiting list
      toward mobile health-delivered physical activity programs.
AB  - CONTEXT: Dialysis patients' lifestyles are associated with low levels of physical
      activity, increasing the chances of being removed from kidney waiting lists or
      dying while awaiting transplant because of increased cardiovascular risk factors
      and deteriorating health conditions. Personalized mobile health (mHealth)
      delivered programs may support their engagement in healthier lifestyles, maintain
      transplant eligibility, and reduce premature mortality. OBJECTIVE: To explore
      barriers and perceptions of physical activity behaviors and gauge interest in
      using mHealth in a physical activity wellness program for dialysis patients on
      the kidney transplant waiting list. PARTICIPANTS AND DESIGN: In-depth key
      informant interviews were conducted with 22 randomly selected dialysis patients
      during dialysis treatment in an urban Southeastern coastal city. A theory-guided
      community-based participatory research approach was used to develop the interview
      content. Constructivist grounded theory guided the data analysis using NVIVO 10
      (QSR Int). The 32-item checklist from the Consolidated Criteria for Reporting
      Qualitative Studies was used in the qualitative reporting. RESULTS: Dialysis
      patients had a mean age of 46 (SD, 10.7) years, 45% were female, and 82% were
      African American. Their mean duration on transplant waiting lists was 6.7 (SD
      4.3) years, and 73% owned smartphones. After saturation was reached, predominant
      themes included (1) physical activity was perceived as optional, (2) social
      support both encouraged and limited physical activity, (3) chronic stress and
      coping influenced physical activity, (4) spirituality provided strength to engage
      in physical activity, (5) self-care management practices varied considerably, and
      (6) high interest (95%) for using mHealth to promote physical activity was found.
      Patients preferred their home and neighborhood environments to intradialytic
      settings for engaging in physical activity.

PMID- 25758798
TI  - Pregnancy-related allograft rejection following heart transplant.
AB  - Current recommendations do not discourage pregnancy in stable, orthotopic heart
      transplant (OHT) recipients who are more than 1 year posttransplant, although a
      highly specialized level of care with a multidisciplinary team is recommended.
      These patients may incur significant risk to themselves, their allograft, and/or
      their fetuses. Recognition and treatment of posttransplant complications in
      pregnancy also may be difficult. Although the risk of recurrent pregnancies in
      patients with peripartum cardiomyopathy (PPCM) is well defined, the risk of
      pregnancy after a PPCM patient has undergone OHT is unknown. A case of severe
      allograft rejection in a woman with a history of PPCM who became pregnant nearly
      3 years after OHT is presented and her subsequent management is described. The
      data available on pregnancy after transplant are based on case reports, registry
      data, and reviews. The decision to become pregnant should be preceded by an
      extensive discussion including the patient, her partner, her obstetrician, and
      the transplant team, reviewing potential risks to her health as well as to her
      allograft and the fetus. Providers should be clear that many questions pertaining
      to pregnancy after transplant remain unanswered, and the patient should be
      comfortable going forward in this situation. 

PMID- 25758799
TI  - Acyclovir versus valganciclovir for preventing cytomegalovirus infection in
      intermediate-risk liver transplant recipients.
AB  - CONTEXT: Cytomegalovirus (CMV) is an opportunistic infection that causes profound
      morbidity and mortality after orthotopic liver transplant (OLT). The CMV
      immunoglobulin G serostatuses of donors and recipients are the main factors
      influencing risk for development of CMV infection after transplant. OBJECTIVE: To
      compare acyclovir and valganciclovir for preventing CMV infection after OLT.
      DESIGN, SETTING, AND PATIENTS: Retrospective assessment of adult OLT recipients
      at intermediate risk for CMV infection at New York Presbyterian Hospital.
      INTERVENTION: All patients received ganciclovir 5 mg/kg intravenously every 12
      hours or valganciclovir 900 mg orally every 12 hours for 7 days after transplant.
      On postoperative day 8, patients received antiviral prophylaxis according to risk
      stratification: acyclovir 800 mg orally 3 times daily in donor
      seronegative/recipient seropositive (D-/R+) patients or valganciclovir 900 mg
      orally once daily in donor seropositive/recipient seropositive (D+/R+) patients.
      MAIN OUTCOME MEASURE: Composite incidence of CMV infection, syndrome, or tissue
      invasive disease. RESULTS: Of 275 OLT recipients, 89 were at intermediate risk
      for CMV infection (29 D-/R+, 60 D+/R+). CMV infection, syndrome, or tissue
      invasive disease occurred in 1 patient (3%) in the D-/R+ group and 5 patients
      (8%) in the D+/R+ group (P=.66). One patient (3%) in the D-/R+ group had a CMV
      infection develop. Five D+/R+ recipients (8%) had CMV infection; 3 of them had
      CMV syndrome (5%), 1 had CMV hepatitis (1.6%), and the other had CMV esophagitis
      (1.6%); all events occurred after prophylaxis was discontinued. The rates of CMV
      infection were similar in D-/R+ patients treated with acyclovir and D+/R+
      patients receiving valganciclovir. This risk-stratified approach to viral
      prophylaxis after OLT resulted in an acceptable rate of CMV infection in D-/R+
      recipients and may avoid the costs and adverse effects associated with
      valganciclovir therapy.

PMID- 25758770
TI  - The development and utility of a novel scale that quantifies the glycemic
      progression toward type 1 diabetes over 6 months.
AB  - OBJECTIVE: We developed a scale to serve as a potential end point for 6-month
      glycemic progression (PS6M) toward type 1 diabetes (T1D) in autoantibody-positive
      relatives of individuals with T1D. RESEARCH DESIGN AND METHODS: The PS6M was
      developed from Diabetes Prevention Trial-Type 1 (DPT-1) data and tested in the
      TrialNet Pathway to Prevention Study (PTP). It is the difference between 6-month
      glucose sum values (30-120 min oral glucose tolerance test values) and values
      predicted for nonprogressors. RESULTS: The PS6M predicted T1D in the PTP (P <
      0.001). The area under the receiver operating chacteristic curve was greater (P <
      0.001) for the PS6M than for the baseline-to-6-month difference. PS6M values were
      higher in those with two or more autoantibodies, 30-0 min C-peptide values <2.00
      ng/mL, or DPT-1 Risk Scores >7.00 (P < 0.001 for all). CONCLUSIONS: The PS6M is
      an indicator of short-term glycemic progression to T1D that could be a useful
      tool for assessing preventive treatments and biomarkers.

PMID- 25758800
TI  - Wound morbidity after kidney transplant.
AB  - CONTEXT: Wound morbidity is an important surgical complication after kidney
      transplant. OBJECTIVE: To assess risk factors for postoperative wound
      complications and the impact of such complications on outcomes of kidney
      transplant. DESIGN AND PATIENTS: Retrospectively, 108 consecutive kidney
      transplant patients between January 2010 and December 2010 were included in the
      analysis. Wound morbidity was defined as a surgical site infection or symptomatic
      lymphocele requiring intervention. Patient, donor, and surgical characteristics
      were reviewed. RESULTS: Eight lymphoceles and 5 surgical site infections occurred
      in 12 patients. Risk factors for wound complications were recipient's age
      (P<.01), body mass index (P=.01), urinary tract infection (P=.01), and prolonged
      postoperative wound drainage (P=.047). Wound morbidity did not increase the
      incidence of delayed graft function, acute rejection, graft failure, or
      mortality. Obesity, recipient's age, urinary tract infection, and prolonged wound
      drainage are risk factors for wound-related complications. Graft and patient
      survival rates are comparable between patients with and without wound-related
      complications.

PMID- 25758803
TI  - Historical perspectives in kidney transplantation: an updated review.
AB  - The present state of success in kidney transplantation, including its benefits to
      patients with end-stage renal failure, was achieved through relentless research,
      both in experimental animal models and human volunteers. Kidney transplantation
      has evolved during the past century thanks to various milestones in surgical
      techniques, immunology, immunosuppressive drugs, expansion of donor sources,
      organ preservation, transplant against immunological barriers (ABO blood group
      incompatible and positive crossmatch transplants), and research on induction of
      tolerance, xenotransplants, and stem cell technology. Despite significant
      improvements in graft and patient survival, several issues still must be
      addressed to reduce the growing number of patients with kidney failure waiting to
      receive organs. This article provides an up-to-date review of the milestones in
      the history of kidney transplantation and highlights strategies to resolve
      current problems faced by patients and the transplant community. 

PMID- 25758802
TI  - Survey of perceptions of health care professionals in the United Kingdom toward
      uterine transplant.
AB  - CONTEXT: Currently, the only 2 options that women with absolute uterine factor
      infertility have for managing their infertility are surragocy or adoption. These
      women may also benefit from a possible future third option: uterine transplant.
      OBJECTIVE: To investigate the opinions and views of UK health care professionals
      toward uterine transplant and rank issues related to uterine transplant by
      importance in order to make uterine transplant transparent and understandable to
      colleagues. DESIGN: Large, in-depth survey investigating health care
      professionals' opinions on uterine transplant. SETTING: Analysis done at Imperial
      College London. PARTICIPANTS: UK transplant professionals (surgeons, nurses,
      operating room staff, and donor coordinators) and obstetricians and gynecologists
      (trainees, members, and fellows of the Royal College of Obstetricians and
      Gynaecologists). INTERVENTION: Questionnaires were given out at hospital grand
      rounds, trainee teaching days, and conferences (national and international). MAIN
      OUTCOME MEASURES: Should uterine transplant take place? Is uterine transplant
      achievable? What is the rank order of importance of key issues related to uterine
      transplant? RESULTS: The study had 528 participants. With respect to overall
      support for uterine transplant and as a possible future therapeutic option for
      absolute uterine factor infertility, 93.8% (n=495) thought that uterine
      transplant should take place if considered appropriate medically, surgically, and
      ethically and 57.2% (n=302) thought it was an achievable objective. Issues
      related to immunology of uterine transplant and pregnancy after uterine
      transplant were unanimously thought of as most important. More effort is required
      to educate health care professionals about all aspects of uterine transplant.

PMID- 25758801
TI  - Postoperative weight gain during the first year after kidney, liver, heart, and
      lung transplant: a prospective study.
AB  - CONTEXT: Studies of all types of organ transplant recipients have suggested that
      weight gain, expressed as an increase in body mass index (BMI), after transplant
      is common. OBJECTIVES: To describe weight gain during the first year after
      transplant and to determine risk factors associated with weight gain with
      particular attention to type of transplant. DESIGN, SETTING, AND PARTICIPANTS: A
      prospective study of 502 consecutive organ transplant recipients (261 kidney, 73
      liver, 29 heart, 139 lung) to identify patterns of BMI change. Measurements were
      made during regular outpatient clinical visits at 2, 6, and 12 months after
      transplant. Data were retrieved from patients' charts and correlated with
      maintenance corticosteroid doses. RESULTS: Overall, mean BMI (SD; range) was 23.9
      (4.5; 13.6-44.1) at 2 months and increased to 25.4 (4.0; 13.0-42.2) by the end of
      the first postoperative year. BMI levels organized by World Health Organization
      categories showed a trend toward overweight/obesity in kidney (53.4%), liver
      (51.5%), heart (51.7%), and lung (33.1%) patients by 12 months after transplant.
      BMI changed significantly (P= .05) for all organ types and between all assessment
      points, except in kidney recipients. Maintenance corticosteroid doses were not a
      predictor of BMI at 12 months after transplant for most patients. CONCLUSIONS:
      Weight gain was common among patients undergoing kidney, liver, heart, and lung
      transplant; however, many showed BMI values close to normality at the end of the
      first year after transplant. In most cases, increased BMI levels were related to
      obesity before transplant and not to maintenance corticosteroid therapy.

PMID- 25758804
TI  - The Kidney Transplant Morbidity Index (KTMI): a simple prognostic tool to help
      determine outcome risk in kidney transplant candidates.
AB  - BACKGROUND: The Kidney Transplant Morbidity Index (KTMI) is a novel prognostic
      morbidity index to help determine the impact that pretransplant comorbid
      conditions have on transplant outcome. OBJECTIVE: To use national data to
      validate the KTMI. DESIGN: Retrospective analysis of the Organ Procurement and
      Transplant Network/United Network for Organ Sharing database. SETTING AND
      PARTICIPANTS: The study sample consisted of 100 261 adult patients who received a
      kidney transplant between 2000 and 2008. MAIN OUTCOME MEASURE: Kaplan-Meier
      survival curves were used to demonstrate 3-year graft and patient survival for
      each KTMI score. Cox proportional hazards regression models were created to
      determine hazards for 3-year graft failure and patient mortality for each KTMI
      score. RESULTS: A sequential decrease in graft survival (0 = 91.2%, 1 = 88.2%, 2
      = 85.4%, 3 = 81.7%, 4 = 77.8%, 5 = 74.0%, 6 = 69.8%, and >= 7 = 68.7) and patient
      survival (0 = 98.2%, 1 = 96.6%, 2 = 93.7%, 3 = 89.7%, 4 = 84.8%, 5 = 80.8%, 6 =
      76.0%, and >= 7 = 74.7%) is seen as KTMI scores increase. The differences in
      graft and patient survival between KTMI scores are all significant (P< .001)
      except between 6 and >= 7. Multivariate regression analysis reveals that KTMI is
      an independent predictor of higher graft failure and patient mortality rates and
      that risk increases as KTMI scores increase. CONCLUSION: The KTMI strongly
      predicts graft and patient survival by using pretransplant comorbid conditions;
      therefore, this easy-to-use tool can aid in determining outcome risk and
      transplant candidacy before listing, particularly in candidates with multiple
      comorbid conditions.

PMID- 25758806
TI  - Health literacy and kidney transplant outcomes.
AB  - CONTEXT: Kidney disease is a common disease that is best treated through kidney
      transplant. The kidney transplant process is complex and can be difficult to
      navigate and most likely requires an adequate amount of health literacy.
      OBJECTIVE: To assess the relationship between health literacy and transplant
      outcomes, including whether a patient was listed for or received a transplant.
      DESIGN: A cross-sectional study measuring patients' health literacy and
      transplant outcomes. SETTING AND PARTICIPANTS: Participants from a single
      transplant center were invited to participate if they were referred to the center
      for transplant and spoke English. Of the 92 patients, 30 (33%) were in the
      vascular access clinic, 31 (34%) were posttransplant, and 31 (34%) were
      pretransplant. INTERVENTION: Health literacy was measured by using 3 tools: Rapid
      Estimate of Adult Literacy of Medicine-Transplant (REALM-T), Newest Vital Sign
      (NVS), and Decision-Making Capacity Assessment Tool (DMCAT). MAIN OUTCOME
      MEASURE: Two dichotomous variables: whether the patient was listed for transplant
      and/or received a transplant. Descriptive and univariate statistics were
      calculated. Six logistic regression models were used to test for a correlation
      between each of the tools and patients' likelihood to be listed for and/or
      receive a transplant. RESULTS: Fifty-three patients (58%) were formally listed
      for a transplant, and 36 (39%) received a transplant. The REALM-T, NVS, and DMCAT
      each significantly predicted whether or not a patient was listed for transplant
      (odds ratios, 1.044, 1.672, and 1.408). The NVS and DMCAT significantly predicted
      whether a patient received a transplant (odds ratios, 1.667 and 1.256). Health
      literacy is a positive and significant predictor of transplant outcomes.
      Clinicians should take assessments of health literacy into account when speaking
      to patients about kidney transplant.

PMID- 25758805
TI  - Applying best practices to designing patient education for patients with end
      stage renal disease pursuing kidney transplant.
AB  - Despite the known benefits of kidney transplant, less than 30% of the 615 000
      patients living with end-stage renal disease (ESRD) in the United States have
      received a transplant. More than 100 000 people are presently on the transplant
      waiting list. Although the shortage of kidneys for transplant remains a critical
      factor in explaining lower transplant rates, another important and modifiable
      factor is patients' lack of comprehensive education about transplant. The purpose
      of this article is to provide an overview of known best practices from the
      broader literature that can be used as an evidence base to design improved
      education for ESRD patients pursuing a kidney transplant. Best practices in
      chronic disease education generally reveal that education that is individually
      tailored, understandable for patients with low health literacy, and culturally
      competent is most beneficial. Effective education helps patients navigate the
      complex health care process successfully. Recommendations for how to incorporate
      these best practices into transplant education design are described. Providing
      more ESRD patients with transplant education that encompasses these best
      practices may improve their ability to make informed health care decisions and
      increase the numbers of patients interested in pursuing transplant. 

PMID- 25758807
TI  - Knowledge of, beliefs about, and perceived barriers to organ and tissue donation
      in Serbian, Macedonian, and Greek Orthodox communities in Australia.
AB  - CONTEXT: Despite the lifesaving benefits of organ and tissue donation, a
      worldwide shortage of suitable and registered donors exists. Although the reasons
      for this shortage are multifactorial, it has been recognized that distinct
      barriers to registration, family discussion, and consent that require targeted
      intervention and action are present among minority cultural, religious, and
      immigrant communities. OBJECTIVE: To explore the knowledge, attitudes, and
      beliefs of 3 orthodox religious communities in Australia (Macedonian, Greek, and
      Serbian Orthodox) and determine the implications for engaging with these
      communities to improve knowledge, attitudes, family discussion, and the ability
      to make an informed decision about donation. DESIGN: Qualitative approach using
      focus groups moderated by researchers and bicultural health workers with the
      assistance of accredited interpreters. PARTICIPANTS: 98 adult members of the
      Greek, Macedonian, and Serbian Orthodox communities in the Illawarra region of
      New South Wales, Australia. RESULTS: Clear barriers to discussing and making an
      informed decision about organ and tissue donation were identified. Knowledge of
      processes and procedures was low and discussion about death (and organ and tissue
      donation) with family members and loved ones was considered taboo. Despite these
      barriers, all 3 communities expressed a desire for more information and
      engagement. Of particular interest were the perspectives of 3 types of "experts":
      medical, religious, and other community members (who had experience with the
      organ and tissue donation system). Future programs designed for orthodox
      religious communities should consider the need for active strategies that
      facilitate information sharing and engagement between community members and these
      3 types of experts.

PMID- 25758810
TI  - Conformationally restricted 3'-modified ABA analogs for controlling ABA
      receptors.
AB  - The physiological functions of abscisic acid (ABA) are regulated by a signal
      transduction pathway involving cytosolic ABA receptors, which include 14
      PYR/PYL/RCAR (PYL) proteins in Arabidopsis. The development of a PYL antagonist
      could be a valuable tool to improve our understanding of the roles of ABA. We
      previously developed 3'-hexylsulfanyl-ABA (AS6), whose S-hexyl chain blocks
      protein phosphatase 2C (PP2C) binding by steric hindrance. This finding not only
      validated our structure-based approach to the design of a PYL antagonist, but
      also provided a basis for the development of a more potent or subclass/subtype
      selective PYL antagonist. In the present study, we synthesized a conformationally
      restricted analog of AS6, namely propenyl-ABA with an O-butyl chain (PAO4), to
      improve the affinity for PYL proteins by reducing the entropic penalty for
      binding to the receptors. In seed germination assays, (+)-PAO4 was a slightly
      stronger antagonist than AS6 in Arabidopsis and a significantly stronger
      antagonist in lettuce. Analysis of the thermodynamic parameters associated with
      the formation of the Arabidopsis PYL-(+)-PAO4 complex revealed that (+)-PAO4
      binds more strongly to PYL5 than AS6 owing to an entropic advantage. In PP2C
      assays, this enhancement effect was observed only for the monomeric PYL subclass
      containing PYL5, suggesting that (+)-PAO4 is more effective than AS6 in
      physiological events involving monomeric PYL proteins as ABA receptors. 

PMID- 25758809
TI  - Clinicopathological characteristics of breast cancer and trends in the management
      of breast cancer patients in Japan: Based on the Breast Cancer Registry of the
      Japanese Breast Cancer Society between 2004 and 2011.
AB  - PURPOSES: We conducted a study to analyze the clinicopathological characteristics
      of breast cancer in Japan registered to the Japanese Breast Cancer Registry of
      the Japanese Breast Cancer Society (JBCS). Trends in the management of breast
      cancer patients in Japan were also analyzed. PATIENTS AND METHODS: More than
      250,000 breast cancer patients were registered to the JBCS registry between 2004
      and 2011. Demographic and clinicopathological factors in newly diagnosed primary
      breast cancer patients were registered to the JBCS through the Web-based system
      from affiliated institutes nationwide. RESULTS: Two distinct peaks were observed,
      in patients in their late 40s and early 60s, in the population-adjusted age
      distribution of breast cancer patients. An increased rate of screen-detected
      breast cancer may contribute to an earlier detection of breast cancer and
      increased rate of non-invasive ductal carcinoma. The positive rate of either ER
      or PgR appears to have increased in recent years. The annual rates of patients
      treated with breast-conserving surgery increased until 2006, but these increases
      stopped in 2007 and thereafter plateaued at approximately 60 %. The annual rates
      of patients treated with sentinel lymph node dissection alone have steadily
      increased. The annual rates of patients treated with preoperative trastuzumab
      plus chemotherapy have also increased, as well as those treated with
      postoperative aromatase inhibitors. The annual rates of patients treated with
      postoperative anthracycline-containing regimens have decreased, whereas those
      treated with postoperative taxane-containing regimens have increased. The
      postoperative use of trastuzumab has markedly increased since 2007. CONCLUSION:
      Although this study was based on the registry database, several unique
      clinicopathological characteristics of breast cancer in Japan have been unveiled.
      Our results suggest that recent trends in the management of breast cancer
      patients in Japan were strongly followed by clinical evidence that originated
      from a number of clinical trials worldwide.

PMID- 25758811
TI  - The glucosinolate breakdown product indole-3-carbinol acts as an auxin antagonist
      in roots of Arabidopsis thaliana.
AB  - The glucosinolate breakdown product indole-3-carbinol functions in cruciferous
      vegetables as a protective agent against foraging insects. While the toxic and
      deterrent effects of glucosinolate breakdown on herbivores and pathogens have
      been studied extensively, the secondary responses that are induced in the plant
      by indole-3-carbinol remain relatively uninvestigated. Here we examined the
      hypothesis that indole-3-carbinol plays a role in influencing plant growth and
      development by manipulating auxin signaling. We show that indole-3-carbinol
      rapidly and reversibly inhibits root elongation in a dose-dependent manner, and
      that this inhibition is accompanied by a loss of auxin activity in the root
      meristem. A direct interaction between indole-3-carbinol and the auxin perception
      machinery was suggested, as application of indole-3-carbinol rescues auxin
      induced root phenotypes. In vitro and yeast-based protein interaction studies
      showed that indole-3-carbinol perturbs the auxin-dependent interaction of
      Transport Inhibitor Response (TIR1) with auxin/3-indoleacetic acid (Aux/IAAs)
      proteins, further supporting the possibility that indole-3-carbinol acts as an
      auxin antagonist. The results indicate that chemicals whose production is induced
      by herbivory, such as indole-3-carbinol, function not only to repel herbivores,
      but also as signaling molecules that directly compete with auxin to fine tune
      plant growth and development. 

PMID- 25758812
TI  - Decreased tumor apparent diffusion coefficient correlates with objective response
      of pediatric low-grade glioma to bevacizumab.
AB  - Recent small, retrospective series suggest bevacizumab may be a therapeutic
      option for recurrent pediatric low-grade glioma (LGG). Assessment of therapeutic
      responses is complicated by the unpredictable natural history of these tumors.
      Because diffusion-weighted imaging quantifies microscopic water motion affected
      by cellular density and histologic features, we hypothesized that it may be
      helpful in monitoring therapeutic response of LGG to bevacizumab. We
      retrospectively reviewed eight consecutive patients, median age 4.8 (range 2.3
      12.3) years at initiation of bevacizumab therapy for recurrent or refractory LGG.
      Patients received 10 mg/kg/dose every 2 weeks (median 16 doses/therapy course).
      Mean apparent diffusion coefficient (ADC) was measured and analyzed in respect to
      tumor volume. Following the first treatment course, seven of eight patients had
      reduced tumor volume (>=25 %) and ADC. The median decrease in tumor volume was
      47% (range -6 to 78 %) and the median decrease in ADC was 14 % (range -5 to 30
      %). The ADC was significantly decreased during therapy, whereas the decrease in
      volume was seen only after therapy completion. There was a positive correlation
      between percent change in tumor volume and ADC (p < 0.05). We report a decrease
      in tumor ADC during initial bevacizumab therapy that is accompanied by a decrease
      in volume following therapy. Imaging changes in microscopic water motion
      associated with histology may be useful in monitoring the therapeutic response of
      LGG to bevacizumab.

PMID- 25758813
TI  - Comparison of Risk Factor Profiles for Primary Open-Angle Glaucoma Subtypes
      Defined by Pattern of Visual Field Loss: A Prospective Study.
AB  - PURPOSE: We explored whether risk factor associations differed by primary open
      angle glaucoma (POAG) subtypes defined by visual field (VF) loss pattern (i.e.,
      paracentral or peripheral). METHODS: We included 77,157 women in the Nurses'
      Health Study (NHS) and 42,773 men in the Health Professionals Follow-up Study
      (HPFS 1986-2010), and incident medical record confirmed cases of paracentral (n =
      440) and peripheral (n = 865) POAG subtypes. We evaluated African heritage,
      glaucoma family history, body mass index (BMI), mean arterial blood pressure,
      diabetes mellitus, physical activity, smoking, caffeine intake, and alcohol
      intake. We used competing risk Cox regression analyses modeling age as the
      metameter and stratified by age, cohort, and event type. We sequentially
      identified factors with the least significant differences in associations with
      POAG subtypes ("stepwise down" approach with P for heterogeneity [P-het] < 0.10
      as threshold). RESULTS: Body mass index was more inversely associated with the
      POAG paracentral VF loss subtype than the peripheral VF loss subtype (per 10
      kg/m2; hazard ratio [HR] = 0.67 [95% confidence interval (CI): 0.52, 0.86] versus
      HR = 0.93 [95% CI: 0.78, 1.10]; P-het = 0.03) as was smoking (per 10 pack-years;
      HR = 0.92 [95% CI: 0.87, 0.98] versus HR = 0.98 [95% CI: 0.94, 1.01]; P-het =
      0.09). These findings were robust in sensitivity analyses using a "stepwise up"
      approach (identify factors that showed the most significant differences).
      Nonheterogeneous (P-het > 0.10) adverse associations with both POAG subtypes were
      observed with glaucoma family history, diabetes, African heritage, greater
      caffeine intake, and higher mean arterial pressure. CONCLUSIONS: These data
      indicate that POAG with early paracentral VF loss has distinct as well as common
      determinants compared with POAG with peripheral VF loss.

PMID- 25758815
TI  - Inner Segment Remodeling and Mitochondrial Translocation in Cone Photoreceptors
      in Age-Related Macular Degeneration With Outer Retinal Tubulation.
AB  - PURPOSE: To quantify impressions of mitochondrial translocation in degenerating
      cones and to determine the nature of accumulated material in the subretinal space
      with apparent inner segment (IS)-like features by examining cone IS
      ultrastructure. METHODS: Human donor eyes with advanced age-related macular
      degeneration (AMD) were screened for outer retinal tubulation (ORT) in macula
      wide, high-resolution digital sections. Degenerating cones inside ORT (ORT cones)
      and outside ORT (non-ORT cones) from AMD eyes and unaffected cones in age-matched
      control eyes were imaged using transmission electron microscopy. The distances of
      mitochondria to the external limiting membrane (ELM), cone IS length, and cone IS
      width at the ELM were measured. RESULTS: Outer retinal tubulation and non-ORT
      cones lose outer segments (OS), followed by shortening of IS and mitochondria. In
      non-ORT cones, IS broaden. Outer retinal tubulation and non-ORT cone IS myoids
      become undetectable due to mitochondria redistribution toward the nucleus. Some
      ORT cones were found lacking IS and containing mitochondria in the outer fiber
      (between soma and ELM). Unlike long, thin IS mitochondria in control cones, ORT
      and non-ORT IS mitochondria are ovoid or reniform. Shed IS, some containing
      mitochondria, were found in the subretinal space. CONCLUSIONS: In AMD, macula
      cones exhibit loss of detectable myoid due to IS shortening in addition to OS
      loss, as described. Mitochondria shrink and translocate toward the nucleus. As
      reflectivity sources, translocating mitochondria may be detectable using in vivo
      imaging to monitor photoreceptor degeneration in retinal disorders. These results
      improve the knowledge basis for interpreting high-resolution clinical retinal
      imaging.

PMID- 25758814
TI  - Lipofuscin redistribution and loss accompanied by cytoskeletal stress in retinal
      pigment epithelium of eyes with age-related macular degeneration.
AB  - PURPOSE: Lipofuscin (LF) and melanolipofuscin (MLF) of the retinal pigment
      epithelium (RPE) are the principal sources of autofluorescence (AF) signals in
      clinical fundus-AF imaging. Few details about the subcellular distribution of AF
      organelles in AMD are available. We describe the impact of aging and AMD on RPE
      morphology revealed by the distribution of AF LF/MLF granules and actin
      cytoskeleton in human tissues. METHODS: Thirty-five RPE-Bruch's membrane
      flatmounts from 35 donors were prepared (postmortem: <=4 hours). Ex vivo fundus
      examination at the time of accession revealed either absence of chorioretinal
      pathologies (10 tissues; mean age: 83.0 +/- 2.6 years) or stages of AMD (25
      tissues; 85.0 +/- 5.8 years): early AMD, geographic atrophy, and late exudative
      AMD. Retinal pigment epithelium cytoskeleton was labeled with AlexaFluor647
      Phalloidin. Tissues were imaged on a spinning-disk fluorescence microscope and a
      high-resolution structured illumination microscope. RESULTS: Age-related macular
      degeneration impacts individual RPE cells by (1) lipofuscin redistribution by (i)
      degranulation (granule-by-granule loss) and/or (ii) aggregation and apparent
      shedding into the extracellular space; (2) enlarged RPE cell area and conversion
      from convex to irregular and sometimes concave polygons; and (3) cytoskeleton
      derangement including separations and breaks around subretinal deposits,
      thickening, and stress fibers. CONCLUSIONS: We report an extensive and systematic
      en face analysis of LF/MLF-AF in AMD eyes. Redistribution and loss of AF granules
      are among the earliest AMD changes and could reduce fundus AF signal attributable
      to RPE at these locations. Data can enhance the interpretation of clinical fundus
      AF and provide a basis for future quantitative studies.

PMID- 25758816
TI  - Age-Related Conjunctival Disease in the C57BL/6.NOD-Aec1Aec2 Mouse Model of
      Sjogren Syndrome Develops Independent of Lacrimal Dysfunction.
AB  - PURPOSE: To investigate parameters of ocular surface disease in C57BL/6.NOD
      Aec1Aec2 (Aec) mice with aging and their correlation with development of Sjogren
      syndrome (SS)-like lacrimal gland (LG) disease. METHODS: Aec and C57BL/6 wild
      type (B6) female mice were evaluated at 4, 12, and 20 weeks of age. Whole LG and
      eyes and adnexa were excised for histology and gene expression analysis and
      evaluated by flow cytometry and immunohistochemistry. Tear volume and goblet cell
      density was measured. Quantitative PCR evaluated T-cell-related cytokine
      expression in cornea and conjunctiva. RESULTS: Both strains showed age-related
      conjunctival goblet cell loss that was more pronounced in the Aec strain and
      significantly greater than in B6 mice at 12 weeks. This was accompanied by CD4+ T
      cell infiltration of the conjunctiva that was greater in Aec strain at 20 weeks.
      Aec mice had higher levels of IL-17A, IL-17R, IL-1alpha, IL-1beta, and TNF-alpha
      in the conjunctiva, and they significantly increase with aging. Aec mice had
      greater lymphocytic infiltration of the LG and conjunctiva at 20 weeks that
      consisted of a mixture of CD4+ and CD8+ cells. Flow cytometry showed a
      significant increase in CD4+ T cells in Aec LG compared to B6 mice. Tear volume
      was significantly increased in both strains at 20 weeks. CONCLUSIONS: Aec mice
      developed greater conjunctival goblet cell loss associated with lymphocytic
      infiltration of the LG and conjunctiva with aging. Increased expression of
      certain T helper or inflammatory cytokines in these tissues was observed in Aec
      mice. The conjunctival disease appeared to be due to inflammation and not a
      decrease in tear volume.

PMID- 25758817
TI  - Inhibition of Corneal Inflammation by the Resolvin E1.
AB  - PURPOSE: To investigate the role of the lipid mediator, resolvin E1 (RvE1), in
      corneal inflammation. METHODS: The effect of RvE1 on stimulated human corneal
      epithelial cells (HCECs) and neutrophils, and mouse macrophage was assessed.
      C57BL/6 mouse corneas were abraded and treated with RvE1 either before or after
      stimulation with lipopolysaccharide (LPS) and antibiotic-killed Pseudomonas
      aeruginosa and Staphylococcus aureus. The levels of CXC chemokines in the cornea
      were quantified, and the presence of neutrophils in corneal infiltrates was
      detected by immunohistochemistry and by in vivo confocal microscopy. The effect
      of RvE1 on apoptosis in the corneal epithelium was assessed using the TUNEL
      assay. RESULTS: RvE1 significantly inhibited cytokine production in HCECs and
      neutrophils, and mouse macrophages and cornea. The development of corneal
      infiltrates, specifically neutrophils, in response to stimulation with LPS, P.
      aeruginosa, and S. aureus was also significantly reduced. There was no apoptotic
      effect of RvE1 on mouse corneal epithelial cells. CONCLUSIONS: RvE1 inhibits
      corneal inflammation induced by LPS, Gram negative (P. aeruginosa) and Gram
      positive (S. aureus) bacteria. These findings indicate that RvE1 as a potential
      anti-inflammatory therapy for patients with corneal inflammation and also, when
      given together with antibiotics, for bacterial keratitis.

PMID- 25758818
TI  - Efficacy of Intravitreal Injections of Antivascular Endothelial Growth Factor
      Agents in a Rat Model of Anterior Ischemic Optic Neuropathy.
AB  - PURPOSE: We investigated the efficacy of intravitreal injections of anti-VEGF
      agents in a rat model of anterior ischemic optic neuropathy. METHODS: We applied
      laser-induced photoactivation on the optic nerve head after intravenously
      administered rose bengal (RB). The rats immediately received an intravitreal
      injection of either ranibizumab or PBS. The density of retinal ganglion cells
      (RGCs) was calculated using retrograde FluoroGold labeling. Visual function was
      assessed by flash visual-evoked potentials (FVEP). We investigated TUNEL assays
      of the retinal sections and ED1 staining of the optic nerve. RESULTS: After
      treatment, the RGC densities in the anti-VEGF-treated rats were not statistically
      significant different from those of the PBS-treated rats (57.0% vs. 40.0% in the
      central retinas; 39.8% vs. 33.6% in midperipheral retinas, both P > 0.05).
      Measurements of FVEP showed no statistically significant differences in preserved
      latency or amplitude of the P1 wave between anti-VEGF and PBS groups (latency 131
      +/- 15 ms versus 142 +/- 14 ms, P = 0.157; amplitude 34 +/- 12 MUv versus 41 +/-
      13 MUv, P = 0.423). Assays of TUNEL showed that there was no statistical
      difference in the number of apoptotic cells in the RGC layers between anti-VEGF
      and PBS groups (7.0 +/- 0.8 cells/high-power field [HPF] versus 7.8 +/- 1.3
      cells/HPF; P = 0.275). In the optic nerves, we did not observe statistically
      significant differences in ED1-positive cells/HPF between anti-VEGF and PBS
      groups (P = 0.675). CONCLUSIONS: Intravitreal injections of anti-VEGF did not
      have a protective effect in the rat model of anterior ischemic optic neuropathy.

PMID- 25758819
TI  - Cultural Adaptation and Translation of Outreach Materials on Autism Spectrum
      Disorder.
AB  - In order to connect with families and influence treatment trajectories, outreach
      materials should address cultural perceptions of the condition, its causes, and
      post-diagnostic care. This paper describes the cultural adaptation and
      translation of the Autism Speaks First 100 Days Kit into Korean for the purpose
      of improving autism spectrum disorder (ASD) diagnosis, assessment, and
      interventions. The goal of this study is to describe a methodology for future
      cross-cultural adaptations and translations of outreach materials on ASD, using
      the Autism Speaks First 100 Days Kit as an exemplar. The research involved two
      stages of qualitative interviews: unstructured individual and group interviews
      with 19 Korean child health and education professionals in Queens, NY, followed
      by structured cultural consensus modeling interviews with 23 Korean mothers, with
      and without children with ASD, in Queens, NY and the greater Washington, DC area.
      We conclude that a systematic approach to cultural translation of outreach
      materials is feasible. Cultural consensus modeling yielded information about
      numerous barriers to care, had a demonstrable effect on the translation of the
      kit, and was efficient when employed with coherent segments of a relatively
      homogeneous population and focused on a single condition.

PMID- 25758820
TI  - A Descriptive Study on the Neonatal Morbidity Profile of Autism Spectrum
      Disorders, Including a Comparison with Other Neurodevelopmental Disorders.
AB  - The aim of this study was to describe the profile of specific neonatal
      morbidities in children later diagnosed with autism spectrum disorder (ASD), and
      to compare this profile with the profile of children with hyperkinetic disorder,
      cerebral palsy, epilepsy or intellectual disability. This is a Danish population
      based cohort study, including all children born in Denmark from 1994, through
      2010, and surviving the first year of life. Children with ASD as a whole have
      significantly elevated rates of a range of neurologic, respiratory, inflammatory,
      and metabolic problems in the neonatal period compared to the general population,
      but there are few if any indicators of a distinctive neonatal morbidity profile
      in ASD compared to other neurodevelopmental outcomes. 

PMID- 25758821
TI  - Social Function and Communication in Optimal Outcome Children and Adolescents
      with an Autism History on Structured Test Measures.
AB  - Youth who lose their ASD diagnosis may have subtle social and communication
      difficulties. We examined social and communication functioning in 44 high
      functioning autism (HFA), 34 optimal outcome (OO) and 34 typically developing
      (TD) youth. Results indicated that OO participants had no autism communication
      symptoms, no pragmatic language deficits, and were judged as likable as TD peers.
      Some group differences were found: OO youth had less insight into social
      relationships and poorer friendship descriptions than TD youth. OO participants
      had attention, self-control, and immaturity difficulties that may impact social
      abilities. However, OO participants were most engaged, friendliest, warmest, and
      most approachable. Overall, OO participants had no social and communicative
      impairments, although some exhibited mild social difficulties that often
      accompany attentional problems. 

PMID- 25758822
TI  - The Association Between Social Skills and Mental Health in School-Aged Children
      with Autism Spectrum Disorder, With and Without Intellectual Disability.
AB  - Autism Spectrum Disorder (ASD) is associated with social skills deficits and co
      occurring mental health difficulties. ASD frequently co-occurs with Intellectual
      Disability (ID). There is scant literature exploring the association between
      social skills and mental health in children with ASD, with or without ID.
      Participants were 292 children aged six to 13 with ASD (217 without ID; 76 with
      Mild ID). Parents and teachers rated social skills and mental health using
      standardised questionnaires. Greater mental health difficulties were associated
      with greater social responsiveness difficulties and poorer social skills across
      the sample. Effect sizes were large. Social skills explained a significant
      proportion of the variance in mental health scores across the sample. The study
      has important implications for treatment and future research. 

PMID- 25758824
TI  - Pathway-based factor analysis of gene expression data produces highly heritable
      phenotypes that associate with age.
AB  - Statistical factor analysis methods have previously been used to remove noise
      components from high-dimensional data prior to genetic association mapping and,
      in a guided fashion, to summarize biologically relevant sources of variation.
      Here, we show how the derived factors summarizing pathway expression can be used
      to analyze the relationships between expression, heritability, and aging. We used
      skin gene expression data from 647 twins from the MuTHER Consortium and applied
      factor analysis to concisely summarize patterns of gene expression to remove
      broad confounding influences and to produce concise pathway-level phenotypes. We
      derived 930 "pathway phenotypes" that summarized patterns of variation across 186
      KEGG pathways (five phenotypes per pathway). We identified 69 significant
      associations of age with phenotype from 57 distinct KEGG pathways at a stringent
      Bonferroni threshold ([Formula: see text]). These phenotypes are more heritable
      ([Formula: see text]) than gene expression levels. On average, expression levels
      of 16% of genes within these pathways are associated with age. Several
      significant pathways relate to metabolizing sugars and fatty acids; others relate
      to insulin signaling. We have demonstrated that factor analysis methods combined
      with biological knowledge can produce more reliable phenotypes with less
      stochastic noise than the individual gene expression levels, which increases our
      power to discover biologically relevant associations. These phenotypes could also
      be applied to discover associations with other environmental factors. 

PMID- 25758823
TI  - Condensin II Regulates Interphase Chromatin Organization Through the Mrg-Binding
      Motif of Cap-H2.
AB  - The spatial organization of the genome within the eukaryotic nucleus is a dynamic
      process that plays a central role in cellular processes such as gene expression,
      DNA replication, and chromosome segregation. Condensins are conserved multi
      subunit protein complexes that contribute to chromosome organization by
      regulating chromosome compaction and homolog pairing. Previous work in our
      laboratory has shown that the Cap-H2 subunit of condensin II physically and
      genetically interacts with the Drosophila homolog of human MORF4-related gene on
      chromosome 15 (MRG15). Like Cap-H2, Mrg15 is required for interphase chromosome
      compaction and homolog pairing. However, the mechanism by which Mrg15 and Cap-H2
      cooperate to maintain interphase chromatin organization remains unclear. Here, we
      show that Cap-H2 localizes to interband regions on polytene chromosomes and co
      localizes with Mrg15 at regions of active transcription across the genome. We
      show that co-localization of Cap-H2 on polytene chromosomes is partially
      dependent on Mrg15. We have identified a binding motif within Cap-H2 that is
      essential for its interaction with Mrg15, and have found that mutation of this
      motif results in loss of localization of Cap-H2 on polytene chromosomes and
      results in partial suppression of Cap-H2-mediated compaction and homolog
      unpairing. Our data are consistent with a model in which Mrg15 acts as a loading
      factor to facilitate Cap-H2 binding to chromatin and mediate changes in chromatin
      organization. 

PMID- 25758826
TI  - Mechanoluminescence of Ba2 MgSi2 O7 doped with Eu(2+) and Dy(3+) phosphor by
      impulsive deformation.
AB  - Di-barium magnesium silicate phosphor doped with Eu(2+) and Dy(3+) was prepared
      using a solid-state reaction technique under a reducing atmosphere. The sample
      underwent impulsive deformation by impact from a piston for mechanoluminescence
      (ML) investigations. The temporal ML characteristics of the phosphor were
      observed, which expressed a single sharp peak with a long decaying period. To
      investigate the luminescence centre responsible for the ML peak, the ML spectrum
      of the phosphor was also observed. The recorded ML spectrum was similar in shape
      and peak wavelength to the photoluminescence (PL) spectrum, which verifies the
      existence of a single emission centre due to the transition of Eu(2+) ions, i.e.
      transitions from any of the sublevels of the 4f(6)5d(1) configuration to the
      (8)S7/2 level of the 4f(7) configuration. Decay rates for different impact
      velocities were also calculated using curve-fitting techniques. The time of the
      ML peak and the rate of decay did not change significantly with respect to
      increasing impact velocity of the load and peak ML intensity varied linearly. The
      mechanism of the ML emission was also discussed.

PMID- 25758825
TI  - Finding a Missing Gene: EFG1 Regulates Morphogenesis in Candida tropicalis.
AB  - Fungi from the genus Candida are common members of the human microbiota; however,
      they are also important opportunistic pathogens in immunocompromised hosts.
      Several morphological transitions have been linked to the ability of these fungi
      to occupy the different ecological niches in the human body. The transcription
      factor Efg1 from the APSES family plays a central role in the transcription
      circuits underlying several of these morphological changes. In Candida albicans,
      for example, Efg1 is a central regulator of filamentation, biofilm formation, and
      white-opaque switching, processes associated with survival in the human host.
      Orthologs of Efg1 are present throughout the Candida clade but, surprisingly, the
      genome sequence of Candida tropicalis failed to uncover a gene coding for Efg1.
      One possibility was that the paralog of Efg1, Efh1, had assumed the function of
      Efg1 in C. tropicalis. However, we show that this gene has only a minor role in
      the morphological transitions mentioned above. Instead, we report here that C.
      tropicalis does have an ortholog of the EFG1 gene found in other Candida species.
      The gene is located in a different genomic position than EFG1 in C. albicans, in
      a region that contains a gap in the current genome assembly of C. tropicalis. We
      show that the newly identified C. tropicalis EFG1 gene regulates filamentation,
      biofilm formation, and white-opaque switching. Our results highlight the
      conserved role of Efg1 in controlling morphogenesis in Candida species and remind
      us that published genome sequences are drafts that require continuous curation
      and careful scrutiny. 

PMID- 25758827
TI  - Planning for the future workforce in hematology research.
AB  - The medical research and training enterprise in the United States is complex in
      both its scope and implementation. Accordingly, adaptations to the associated
      workforce needs present particular challenges. This is particularly true for
      maintaining or expanding national needs for physician-scientists where training
      resource requirements and competitive transitional milestones are substantial.
      For the individual, these phenomena can produce financial burden, prolong the
      career trajectory, and significantly influence career pathways. Hence, when
      national data suggest that future medical research needs in a scientific area may
      be met in a less than optimal manner, strategies to expand research and training
      capacity must follow. This article defines such an exigency for research and
      training in nonneoplastic hematology and presents potential strategies for
      addressing these critical workforce needs. The considerations presented herein
      reflect a summary of the discussions presented at 2 workshops cosponsored by the
      National Heart, Lung, and Blood Institute and the American Society of Hematology.

PMID- 25758828
TI  - How I treat hemophagocytic lymphohistiocytosis in the adult patient.
AB  - Hemophagocytic lymphohistiocytosis (HLH) is a devastating disorder of
      uncontrolled immune activation characterized by clinical and laboratory evidence
      of extreme inflammation. This syndrome can be caused by genetic mutations
      affecting cytotoxic function (familial HLH) or be secondary to infectious,
      rheumatologic, malignant, or metabolic conditions (acquired HLH). Prompt
      recognition is paramount and, without early treatment, this disorder is
      frequently fatal. Although HLH is well described in the pediatric population,
      less is known about the appropriate work-up and treatment in adults. Here, we
      review the clinical characteristics, diagnosis, and treatment of HLH in adults. 

PMID- 25758829
TI  - Prognostic value of FDG-PET prior to autologous stem cell transplantation for
      relapsed and refractory diffuse large B-cell lymphoma.
AB  - High-dose chemotherapy (HDT) plus autologous stem cell transplantation (ASCT) is
      the standard of care for chemosensitive relapsed and refractory diffuse large B
      cell lymphoma (rel/ref DLBCL). Interim restaging with functional imaging by
      positron emission tomography using (18)F-deoxyglucose (FDG-PET) has not been
      established after salvage chemotherapy (ST) and before HDT-ASCT by modern
      criteria. Herein, we evaluated 129 patients with rel/ref DLBCL proceeding to HDT
      ASCT, with ST response assessment by FDG-PET according to the contemporary
      Deauville 5-point scale. At 3 years, patients achieving a Deauville response of 1
      to 3 to ST experienced superior progression-free survival (PFS) and overall
      survival (OS) rates of 77% and 86%, respectively, compared with patients
      achieving Deauville 4 (49% and 54%, respectively) (P < .001). No other pre-HDT
      ASCT risk factors significantly impacted PFS or OS. Despite achieving remission
      to ST, patients with Deauville 4 should be the focus of risk-adapted
      investigational therapies. 

PMID- 25758836
TI  - Activated carbons from end-products of tree nut and tree fruit production as
      sorbents for removing methyl bromide in ventilation effluent following
      postharvest chamber fumigation.
AB  - End-products of tree nuts and tree fruits grown in California, USA were evaluated
      for the ability to remove methyl bromide (MB) from ventilation effluent following
      postharvest chamber fumigation. Activated carbon sorbents from walnut and almond
      shells as well as peach and prune pits were prepared using different methods of
      pyrolysis, activation, and quenching. Each source and preparation was evaluated
      for yield from starting material (%, m/m) and performance on tests where MB
      containing airstreams were directed through a columnar bed of the activated
      carbon in an experimental apparatus, termed a parallel adsorbent column tester,
      which was constructed as a scaled-down model of a chamber ventilation system. We
      report the number of doses needed to first observe the breakthrough of MB
      downstream of the bed and the capacity of the activated carbon for MB (%, m/m)
      based on a fractional percentage of MB mass sorbed at breakthrough relative to
      mass of the bed prior to testing. Results were based on a novel application of
      solid-phase microextraction with time-weighted averaging sampling of MB
      concentration in airstreams, which was quantitative across the range of
      fumigation-relevant conditions and statistically unaffected by relative humidity.
      Activated carbons from prune pits, prepared either by steam activation or carbon
      dioxide activation coupled to water quenching, received the greatest number of
      doses prior to breakthrough and had the highest capacity, approximately 12-14%,
      outperforming a commercially marketed activated carbon derived from coconut
      shells. Experimental evidence is presented that links discrepancy in performance
      to the relative potential for activated carbons to preferentially sorb water
      vapor relative to MB.

PMID- 25758837
TI  - Validation of the omega-3 fatty acid intake measured by a web-based food
      frequency questionnaire against omega-3 fatty acids in red blood cells in men
      with prostate cancer.
AB  - BACKGROUND/OBJECTIVES: The objective of this study was to evaluate the ability of
      a web-based self-administered food frequency questionnaire (web-FFQ) to assess
      the omega-3 (omega-3) fatty acids (FAs) intake of men affected with prostate
      cancer (PCa) against a biomarker. SUBJECTS/METHODS: The study presented herein is
      a sub-study from a phase II clinical trial. Enrolled patients afflicted with PCa
      were included in the sub-study analysis if the FA profiles from the red blood
      cell (RBC) membranes and FA intakes at baseline were both determined at the time
      of the data analysis (n=60). Spearman's correlation coefficients were calculated
      to estimate the correlations between FA intakes and their proportions in the RBC
      membranes. RESULTS: Intakes of eicosapentaenoic acid (EPA) and docosahexaenoic
      acid (DHA) were highly correlated with their respective proportions in the RBC
      membranes (both rs=0.593, P<0.0001). Correlation between alpha-linolenic acid
      (ALA) intake and its proportion in RBC was not significant (rs=0.130, P=0.332).
      Correlations were observed between fatty fish intake and total omega-3 FAs
      (rs=0.304, P=0.02), total long-chain omega-3 FAs (rs=0.290, P=0.03) and DHA
      (rs=0.328, P=0.01) in RBC membranes. CONCLUSIONS: This study has shown that the
      web-FFQ is an accurate tool to assess total long-chain omega-3 FAs, EPA and DHA
      but not ALA intake in clinical trials and epidemiological studies carried out in
      men with PCa.

PMID- 25758839
TI  - Acid-base disturbances may complicate the diagnosis of refeeding syndrome.

PMID- 25758838
TI  - Effect of weight loss on mortality in overweight and obese nursing home residents
      during a 5-year follow-up.
AB  - BACKGROUND/OBJECTIVES: The objective of this study was to ascertain the effect of
      weight loss over the course of 1 year on 5-year mortality in old nursing home
      (NH) residents in different classes of body mass index (BMI). SUBJECTS/METHODS: A
      longitudinal study was conducted on 161 NH residents aged ? 70 years at the
      Istituto di Riposo per Anziani, Padova, Italy. Data were collected using a
      comprehensive geriatric assessment at baseline and at a 1-year follow-up visit.
      Mortality was recorded over a 5-year follow-up. We divided our sample into four
      groups using as cutoffs a BMI of 25 and a weight gain or loss of 5% at 1 year
      (BMI ? 25 and weight stable/gain, BMI ? 25 and weight loss, BMI<25 and weight
      stable/gain and BMI <25 and weight loss). RESULTS: People with a BMI ? 25 and
      weight loss suffered the worst decline in activities of daily living, whereas
      those with a BMI <25 and weight loss had the most significant decline in
      nutritional status, which coincided with the worst decline in the
      Multidimensional Prognostic Index among the groups whose weight changed. Compared
      with those with a BMI ? 25 and weight stable/gain (reference group), those with a
      BMI <25 were at the highest risk of dying (in association with weight loss:
      hazard ratio HR=3.60, P=0.005; in association with weight stable/gain: HR=2.45,
      P=0.01), and the mortality risk was also increased in people with a BMI ? 25 and
      weight loss (HR=1.74, P=0.03). CONCLUSIONS: In conclusion, weight loss increases
      the mortality risk in frail, disabled NH residents, even if they are overweight
      or obese.

PMID- 25758840
TI  - Acceptability of programme budgeting and marginal analysis as a tool for routine
      priority setting in Indigenous health.
AB  - OBJECTIVE: This study aimed to examine the acceptability of programme budgeting
      and marginal analysis (PBMA) as a tool for priority setting in the Indigenous
      health sector. METHODS: The study uses a mix of quantitative and qualitative
      methods. A survey of key decision makers in Indigenous health in Victoria was
      conducted to assess the acceptability of PBMA as a potential tool for priority
      setting. Respondents comprised 24 bureaucrats from the Victorian Department of
      Human Services (DHS) and 26 senior executives from the aboriginal community
      controlled health sector (ACCHS) in Victoria. The survey instrument included both
      closed-ended and open-ended questions and was administered face-to-face by a
      trained researcher in 2007-2008. Closed-ended questions were analysed using
      descriptive statistics, and content analysis was used for the open-ended ones.
      RESULTS: The PBMA was well received as having the potential to improve priority
      setting processes in Indigenous health. Sixty-nine percent of the DHS respondents
      felt that PBMA was acceptable as a routine decision-making tool, and nearly 80%
      of ACCHS respondents thought that PBMA was intuitively appealing and would most
      probably be an acceptable priority setting approach in their organisations. The
      challenges of using PBMA were related to resource constraints and data intensity.
      CONCLUSION: Programme budgeting and marginal analysis is potentially acceptable
      within the ACCHS and was perceived as useful in terms of assisting the decision
      maker to maximise health outcomes, but data systems need to be re-oriented to
      address its significant data needs. IMPLICATION: Proper guidelines need to be
      developed to facilitate PBMA application within the Indigenous-controlled
      community health sector. Copyright (c) 2015 John Wiley & Sons, Ltd.

PMID- 25758841
TI  - Missing laboratory test data in electronic general practice records: analysis of
      rheumatoid factor recording in the clinical practice research datalink.
AB  - PURPOSE: To investigate whether information from the literature could be used to
      identify periods of practice data in an electronic healthcare database during
      which rheumatoid factor (RF) test results are likely to be missing-not-at-random
      (MNAR). METHODS: RF tests recorded in the Clinical Practice Research Datalink
      (CPRD) were identified and defined as having a positive, negative or missing
      result. The proportion of positive test results was then calculated based on (i)
      complete-case analysis (ii) after restriction to tests from practice years with
      no missing test results and (iii) following multiple imputation of missing test
      results. The same three analyses were then carried out after excluding practice
      years with a proportion of positive tests incompatible with the missing
      completely at random (MCAR) assumption. RESULTS: We identified 127,969 RF test
      records, 30.4% of which did not have an associated test result. Among tests with
      results available, 19% were positive. Both multiple imputation of the 38,867
      missing test results and restriction of the study population to the 491 practice
      years with complete data had little impact on the percentage of positive tests.
      Following exclusion of the 544 practice years in which data were likely to be
      MNAR the percentage of positive tests in all analyses decreased to ~7%.
      CONCLUSIONS: Recording of RF tests and RF test results in the CPRD is incomplete,
      with data likely to be MNAR in many practices. Exclusion of practice years with a
      high proportion of positive tests brought the distribution of positive tests in
      the study in line with the literature.

PMID- 25758842
TI  - Epileptic headache: need for a better knowledge.

PMID- 25758843
TI  - Vincristine-induced neuropathy: Atypical electrophysiological patterns in
      children.
AB  - INTRODUCTION: Vincristine is an antimitotic agent used for treatment of leukemia,
      lymphomas, and cancers. Its main side effect is a dose-related, length-dependent
      (LD) axonal neuropathy. METHODS: We performed electrodiagnostic (EDx)
      examinations in 17 children who had been treated with vincristine and who
      presented with the clinical picture of a peripheral neuropathy. RESULTS: The mean
      dose of vincristine was 8.5 +/- 4.0 mg/m(2) . Clinical motor symptoms were more
      frequent and more severe than sensory ones. Thirteen children presented with a
      motor deficit, 4 of whom could no longer walk. EDx examination showed an axonal
      neuropathy with a non-length-dependent (NLD) pattern in 9 children and an LD
      pattern in 8. A major motor predominance was encountered in 12 patients.
      CONCLUSIONS: The electrophysiological and clinical motor predominance described
      differs from the mainly sensory neuropathy reported in adults. Incomplete
      myelination due to young age may have resulted in greater sensitivity of some
      nerves to neurotoxic agents.

PMID- 25758844
TI  - Oral Medicine referrals at a hospital-based practice in the United States.
AB  - OBJECTIVE: The objective of this study was to characterize the outpatient oral
      medicine (OM) clinic at Brigham and Women's Hospital (BWH), with particular
      emphasis on patient demographic characteristics and referral patterns. MATERIALS
      AND METHODS: A retrospective case record review of all initial consultations with
      OM experts at BWH from 2008 to 2010 was conducted. Data included demographic
      information, type of medical insurance, reason for referral, referring doctor's
      specialty, and distance between the patient's home and the referring doctor as
      well as BWH, number of prior doctors seen for the presenting problem (per patient
      report), tests ordered at the consultation visit, and clinical diagnoses.
      RESULTS: There were 1043 new outpatient consultation visits. Patients lived a
      median distance of 9.5 miles from the referring doctor and 18.9 miles from BWH
      and saw a median of one doctor (range 0-9) before consultation. Two thirds of
      patients were referred by physicians. The most common diagnoses included immune
      mediated mucosal conditions (27.2%), orofacial pain disorders (25.1%), benign
      tumors or neoplasms (10.3%), and dysplasia and cancerous conditions (7.6%).
      Biopsy was the most frequent test performed at consultation. CONCLUSIONS:
      Patients with oral conditions often see more than one doctor, before being
      referred to an OM expert and typically travel twice the distance to the expert
      compared with that between their home and the referring doctor. Equal efforts
      should be made to increase awareness of the importance of the specialty of OM
      among dentists, physicians, and the public.

PMID- 25758845
TI  - Associations between bacteremia from oral sources and distant-site infections:
      tooth brushing versus single tooth extraction.
AB  - OBJECTIVES: To determine the impact of antibiotic prophylaxis (AP) on the
      incidence of bacteremia caused by oral bacterial species associated with
      infective endocarditis (IE) and prosthetic joint infections (PJIs) and to compare
      the incidence of following tooth brushing versus single tooth extraction. STUDY
      DESIGN: Bacterial species in blood following single tooth extraction, with or
      without AP, and tooth brushing(1) were compared with IE- and PJI-associated
      bacteria reported in the literature. RESULTS: Of the 98 bacterial species
      identified in blood following single tooth extraction and tooth brushing, 32(1)
      and 12 were species were associated with IE and PJI, respectively. AP decreased
      the frequency of IE- and PJI-causing oral bacterial species in blood; however,
      single tooth extraction versus brushing resulted in bacteremia with IE- and PJI
      causing species with similar frequencies: 65% versus 56% for IE, and 31% versus
      28% for PJI. CONCLUSIONS: Although AP significantly decreased the incidence of
      bacteremia, the similarity between the incidence of bacteremia following brushing
      and extraction undermines AP as an effective strategy for the prevention of these
      distant-site infections.

PMID- 25758846
TI  - Treatment outcomes of the intraoral approach for a simple ranula.
AB  - OBJECTIVE: The study sought to determine the optimal surgical treatment of a
      simple ranula and analyzed the clinical characteristics and treatment outcomes of
      a simple ranula in our hospital. METHODS: A retrospective review was performed to
      evaluate patients with a diagnosis of a simple ranula at Chonnam National
      University Hwasun Hospital from November 2007 to August 2013. Clinical data on
      simple ranulas that were reviewed included gender, age, symptoms, duration of
      symptoms, location and size of lesion, surgical procedures, complications,
      recurrence, and follow-up. RESULTS: The 24 patients included in the study
      comprised 10 males and 14 females. Sixteen patients (66.7%) did not have a prior
      treatment history. Eight patients had undergone previous treatment, which
      included Picibanil injection sclerotherapy, incision and drainage, and
      micromarsupialization. The simple ranula recurred after excision of the ranula
      and the sublingual gland in only one (4.2%) of 24 cases. In eight patients who
      had undergone previous treatment, there was no recurrence after excision of the
      ranula and sublingual gland. There were no major complications and recurrences in
      the patients with recurrent simple ranulas. CONCLUSIONS: Excision of the ranula
      and the sublingual gland via intraoral approach is the optimal treatment for a
      simple ranula, even in the case of a recurrent simple ranula.

PMID- 25758847
TI  - Oral squamous cell carcinoma in a patient with keratitis-ichthyosis-deafness
      syndrome: a rare case.
AB  - Keratitis-ichthyosis-deafness (KID) syndrome is a rare form of ectodermal
      dysplasia with significant visual and auditory impairment. Pathogenesis involves
      a mutation in the GJB2 gene, which encodes connexin-26, a protein in the
      epithelial gap junctions thought to be involved in the differentiation of
      ectodermally derived tissues. Affected patients are also at increased risk for
      the epithelial malignancies. To our knowledge, nearly 100 cases of KID syndrome,
      including 19 with squamous cell carcinoma (SCC) complications, have been reported
      worldwide. We report here a patient with KID syndrome who developed an ulcerative
      oral lesion causing him significant discomfort; he was subsequently diagnosed
      with oral SCC. We review the clinical presentation and symptomatology, including
      those affecting the oral cavity for this syndrome and highlight the importance of
      multidisciplinary collaboration and life-long screening aimed at prevention of
      the evolving complications. 

PMID- 25758848
TI  - Dietary Aloe vera supplementation on growth performance, some haemato-biochemical
      parameters and disease resistance against Streptococcus iniae in tilapia (GIFT).
AB  - This study investigated effects of dietary Aloe vera on growth performance, some
      haemato-biochemical parameters and disease resistance against Streptococcus iniae
      in tilapia (GIFT). Five groups were designed including a basal diet (control) and
      100% A. vera powder incorporated in fish feed at 0.5% 1%, 2%, and 4%/kg feed,
      which were administered for 8 weeks. Fish fed 0.5%, 1%, and 2% A. vera
      supplemented diet significantly improved (p < 0.05) weight gain, absolute growth
      rate and specific growth rate. Feed intake significantly increased in fish fed
      with A. vera diet at 1% and 2%/kg feed. Feed efficiency ratio, feed conversion
      ratio, and hepatosomatic index were significantly enhanced in 4% A. vera
      supplemented fish over unsupplemented ones (p < 0.05). Several haemato
      biochemical indices were examined before and after fish were challenged with S.
      iniae pathogen containing 7.7 * 10(6) CFU cells mL(-1). A. vera supplemented fish
      showed a significant increase (p < 0.05) in red blood cells, hematocrits (Hb),
      hemoglobin (Hb), white blood cells (WBC), neutrophils, monocytes, eosinophils,
      serum total protein, glucose and cortisol after challenge when compared to
      unsupplemented ones. Meanwhile, 4% A. vera supplemented fish showed a decrease (p
      < 0.05) in RBC, Hb, Ht, WBC, and mean corpuscular hemoglobin (MCH) after
      challenge compared to unsupplemented ones and other supplemented ones. In
      addition, lower mean corpuscular volume values (MCV) (p < 0.05) were observed in
      fish fed with A. vera diet at 2% and 4% A. vera/kg feed than those fed
      unsupplemented diet. Unchallenged fish fed 0.5%, 1%, and 2% A. vera showed
      significantly higher values (p < 0.05) of mean corpuscular hemoglobin
      concentration (MCHC) than those fed unsupplemented diet and 4% A. vera
      supplemented diet. There was a significant increase (p < 0.05) in the neutrophil
      to lymphocyte ratio (N/L) within experimental groups after challenge; N/L ratio
      in A. vera unsupplemented fish and those supplemented with A. vera diet at 1%/kg
      feed increased significantly (p < 0.05) throughout challenge period; while those
      fed 4% A. vera supplemented diet maintained higher values at all experimental
      stages among groups. There was a significant correlation (p < 0.05, r = 0.53)
      between N/L ratio and glucose concentration, 96 h after challenge. Aloe had no
      significant effect (p > 0.05) on the survival of the fish when compared to the
      control; no mortality was recorded in challenge trial. Overall, our results
      indicated that dietary aloe supplementation could improve growth, feed
      utilization, and haemato-biochemical parameters of cultured tilapia.

PMID- 25758849
TI  - Antimicrobial considerations in the perioperative patient.
AB  - Surgical site infections are among the complications that can be reduced with the
      timely implementation of appropriate antimicrobial therapy. A 3-D approach to
      judicious antimicrobial use focuses on the de-escalation of systemic
      antimicrobial therapy, design of dosing regimens, and decontamination of the
      surgeon, patient, and environment. De-escalation can be accomplished in part
      through proper antimicrobial prophylaxis. Dosing regimens should be designed to
      maximize efficacy and minimize resistance. Decontamination includes disinfection
      of inanimate surfaces and timely application of appropriate antiseptics at
      concentrations that maximize efficacy. 

PMID- 25758850
TI  - Current concepts in minimally invasive surgery of the abdomen.
AB  - Minimally invasive surgery of the abdomen constitutes an increasingly common and
      developed set of surgical options in small animal veterinary patients. In
      addition to established procedures, such as laparoscopic gonadectomy and
      biopsies, more advanced procedures, such as adrenalectomy, cholecystectomy,
      cisterna chyli ablation, and lymph node extirpation, are described. Some
      laparoscopic procedures have been reported using different techniques or
      approaches, reflecting the field's progression beyond its infancy. Advances in
      equipment and experience among an ever-growing group of veterinary surgeons are
      expected to result in progressively more widespread adoption of minimally
      invasive procedures. 

PMID- 25758851
TI  - Current concepts in oncologic surgery in small animals.
AB  - Surgical oncology is experiencing rapid transition in veterinary medicine. Mast
      cell tumors and soft tissue sarcomas are two of the most common neoplasms in
      small animal patients. Clinicians should be familiar with the need for staging
      and the procedures involved in treating patients with these tumors. Clinicians
      should be comfortable with available adjuvant therapies and when to use them in
      certain patients. 

PMID- 25758852
TI  - Functionalization of fluorinated benzenesulfonamides and their inhibitory
      properties toward carbonic anhydrases.
AB  - Substituted tri- and tetrafluorobenzenesulfonamides were designed, synthesized,
      and evaluated as high-affinity and isoform-selective carbonic anhydrase (CA)
      inhibitors. Their binding affinities for recombinant human CA I, II, VA, VI, VII,
      XII, and XIII catalytic domains were determined by fluorescent thermal shift
      assay, isothermal titration calorimetry, and a stopped-flow CO2 hydration assay.
      Variation of the substituents at the 2-, 3-, and 4-positions yielded compounds
      with a broad range of binding affinities and isoform selectivities. Several 2,4
      substituted-3,5,6-trifluorobenzenesulfonamides were effective CA XIII inhibitors
      with high selectivity over off-target CA I and CA II. 3,4-Disubstituted-2,5,6
      trifluorobenzenesulfonamides bound CAs with higher affinity than 2,4
      disubstituted-3,5,6-trifluorobenzenesulfonamides. Many such fluorinated
      benzenesulfonamides were found to be nanomolar inhibitors of CA II, CA VII, tumor
      associated CA IX and CA XII, and CA XIII. X-ray crystal structures of inhibitors
      bound in the active sites of several CA isoforms provide structure-activity
      relationship information for inhibitor binding affinities and selectivity.

PMID- 25758853
TI  - Review on cardiovascular risk prediction.
AB  - The objectives were to review the currently available and widely used
      cardiovascular risk assessment models and to examine the evidence available on
      new biomarkers and the nonclinical measures in improving the risk prediction in
      the population level. Identification of individuals at risk of cardiovascular
      disease (CVD), to better target prevention and treatment, has become a top
      research priority. Cardiovascular risk prediction has progressed with the
      development and refinement of risk prediction models based upon established
      clinical factors, and the discovery of novel biomarkers, lifestyle, and social
      factors may offer additional information on the risk of disease. However, a
      significant proportion of individuals who have a myocardial infarction still are
      categorized as low risk by many of the available methods. Although novel
      biomarkers can improve risk prediction, including B-type natriuretic peptides
      which have shown the best predictive capacity per unit cost, there is concern
      that the use of risk prediction strategies which rely upon new/or expensive
      biomarkers could further broaden social inequalities in CVD. In contrast,
      nonclinical factors such as work stress, social isolation, and early childhood
      experience also appear to be associated with cardiovascular risk and have the
      potential to be utilized for the baseline risk stratification at the population
      level. A stepwise approach of nonclinical methods followed by risk scores
      consisting of clinical risk factors may offer a better option for initial and
      subsequent screening, preserving more specialized approaches including novel
      biomarkers for enhanced risk stratification at population level in a cost
      effective manner. 

PMID- 25758854
TI  - Risk factors for malaria and adverse birth outcomes in a prospective cohort of
      pregnant women resident in a high malaria transmission area of Papua New Guinea.
AB  - BACKGROUND: Low birth weight (LBW), anaemia and malaria are common in Papua New
      Guinean women. METHODS: To identify risk factors for LBW, anaemia and preterm
      delivery (PTD), pregnant women recruited into a cohort study in Madang, Papua New
      Guinea, were followed to delivery. RESULTS: Of 470 women enrolled, delivery data
      were available for 328 (69.7%). By microscopy, 34.4% (113/328) of women had
      malaria parasitaemia at enrolment and 12.5% (41/328) at delivery; at each time
      point, PCR detected sub-microscopic parasitaemia in substantially more. Most
      infections were with Plasmodium falciparum; the remainder being predominantly P.
      vivax. Anaemia and smoking were associated with lower birth weight, and LBW
      (16.7%; 51/305) and PTD (21.8%; 63/290) were common. Histopathologically
      diagnosed chronic placental malaria was associated with LBW (adjusted odds ratio
      [aOR] 3.3; p=0.048) and PTD (aOR 4.2; p=0.01). Lack of maternal education
      predisposed to PTD. Sub-microscopic parasitaemia at delivery appeared to increase
      the risk of LBW. Of the genetic polymorphisms, Southeast Asian ovalocytosis,
      alpha(+)-thalassaemia and complement receptor 1 (CR1) deficiency, a CR1
      heterozygous genotype was associated with decreased risk of anaemia and
      substantial but non-significant effects were noted in other comparisons.
      CONCLUSIONS: In coastal Papua New Guinea, malaria and anaemia are important
      causes of adverse pregnancy outcomes.

PMID- 25758855
TI  - Enteric pathogens of food sellers in rural Gambia with incidental finding of
      Myxobolus species (Protozoa: Myxozoa).
AB  - BACKGROUND: Ongoing surveillance of enteric pathogens of public health
      significance among casual food sellers is undertaken in many resource-limited
      countries. We report the results of a survey in Kiang West province, The Gambia,
      and provide an exemplar methodology for such surveys in resource-limited
      laboratories. METHODS: Unpreserved, unrefrigerated stool samples were subjected
      to Salmonella, Shigella and agar plate culture for rhabditoid nematodes. Direct
      microscopy, formalin-ethyl acetate concentration and iron-hematoxylin staining
      was performed later, following preservation. RESULTS: Of 128 specimens received,
      no Shigella spp. was recovered, while four serovars of non-typhoidal Salmonella
      enterica, including Chandans, were isolated. Pathogenic parasitic infections were
      Necator americanus 10/128 (7.8%), Strongyloides stercoralis 3/128 (2.8%),
      Blastocystis species 45/128 (35.1%), Entamoeba histolytica complex 19/128 (14.8%)
      and Giardia intestinalis 4/128 (3.1%). A single case each of Hymenolepis diminuta
      and S. mansoni infection were detected. In one participant, myxozoan spores
      identical to those of Myxobolus species were found. CONCLUSIONS: Rare parasitoses
      and serovars of Salmonella enterica may occur relatively commonly in rural
      Africa. This paper describes intestinal pathogens found in a cohort of food
      sellers in such a setting. Furthermore, it describes two parasites rarely
      recovered from humans and demonstrates the need for methods other than microscopy
      to detect S. stercoralis infections.

PMID- 25758856
TI  - MicroRNAs in Esophageal Adenocarcinoma: Functional Significance and Potential for
      the Development of New Molecular Disease Markers.
AB  - Esophageal adenocarcinoma (EAC) originates from the neoplastic changes in the
      esophageal epithelium. Barrett's esophagus (BE) precedes EAC. In BE metaplasia,
      the normal stratified squamous epithelium is replaced by the intestinal columnar
      epithelium. Esophageal metaplasia might further progress to dysplasia, neoplasia,
      and EAC. The neoplastic progression from BE to EAC is accompanied with marked
      histological and molecular changes including deregulation of key signaling
      pathways and expression of various genes including microRNA (miRNA). To date,
      stable and progressive changes in expression levels of different miRNA subsets
      are shown for each stage of EAC carcinogenesis. This suggests that miRNAs might
      become promising markers for BE/EAC diagnosis and prognosis of survival of EAC
      patients and lymph node tumor metastases. Development of new molecular markers
      based on the assessment of miRNAs circulating in patients' biofluids would
      improve the effectiveness and cost-effectiveness of esophageal cancer
      surveillance regimens and open new possibilities for high throughput screening
      programs to identify BE patients who are at high-risk for the development of
      highgrade dysplasia or progression to EAC. 

PMID- 25758857
TI  - New spastic paraplegia phenotype associated to mutation of NFU1.
AB  - Recently an early onset lethal encephalopathy has been described in relation to
      mutations of NFU1, one of the genes involved in iron-sulfur cluster metabolism.
      We report a new NFU1 mutated patient presenting with a milder phenotype
      characterized by a later onset, a slowly progressive spastic paraparesis with
      relapsing-remitting episodes, mild cognitive impairment and a long survival. The
      early white matter abnormalities observed on MRI was combined with a mixed
      sensory-motor neuropathy in the third decade. Our case clearly suggests the
      importance of considering NFU1 mutation in slowly evolving leukoencephalopathy
      with high glycine concentration. 

PMID- 25758858
TI  - Is copper imbalance an environmental factor influencing keratoconus development?
AB  - Keratoconus is a bilateral disease characterized by progressive corneal thinning
      leading to irregular astigmatism that results in significant visual impairment.
      Despite extensive research, the exact etiopathogenesis of keratoconus remains
      unknown. Many copper-dependent enzymes such as superoxide dismutases, cytochrome
      c oxidase and lysyl oxidase have been shown to be altered in keratoconic corneas,
      and a decrease of copper levels in the diseased tissue has been reported as well.
      We propose a hypothesis linking all the putative pathways of keratoconus
      development and suggest that copper imbalance in corneal tissue may be an
      independent risk factor for the disease. The assessment of copper levels and its
      distribution in keratoconic corneas warrants further investigation. 

PMID- 25758859
TI  - Myoblast fusion: playing hard to get.
AB  - In Drosophila myoblast fusion, the fusing cell invades another by actin-enriched
      protrusion. In this issue of Developmental Cell, Kim et al. (2015) examine the
      myoblast fusion mechanism from the perspective of the "receiving" cell and report
      that fusion depends on the ability of this cell to stiffen its actomyosin cortex.

PMID- 25758860
TI  - Weaning gives beta cells license to regenerate.
AB  - Pancreatic beta cell proliferation is high at birth and then rapidly declines. In
      this issue of Developmental Cell,Stolovich-Rain et al. (2015) show that beta
      cells' capacity to increase proliferation in response to injury is unexpectedly
      not acquired until after weaning-related nutritional changes trigger a metabolic
      and regenerative competence program.

PMID- 25758861
TI  - Epithelial morphogenesis: apoptotic forces drive cell shape changes.
AB  - Studying how cells produce and transmit forces that drive morphogenesis is
      critical to understanding organismal development. A new paper by Monier et al.
      (2015) identifies an apicobasal actomyosin cable that characterizes apoptotic
      cells and contributes force(s) for cell sheet bending.

PMID- 25758863
TI  - Distinct polarity cues direct Taz/Yap and TGFbeta receptor localization to
      differentially control TGFbeta-induced Smad signaling.
AB  - We and others have shown that the Hippo pathway effectors TAZ and YAP direct Smad
      activity to regulate TGFbeta family-induced cellular responses in stem cell and
      cancer biology. In polarized epithelial cells we showed that the Crumbs complex
      promotes Hippo-dependent cytoplasmic TAZ/YAP localization that restricts TGFbeta
      induced Smad nuclear accumulation and activity. In this Developmental Cell issue,
      basal-lateral restriction of TGFbeta receptors is proposed as the sole mechanism
      suppressing Smad signaling in epithelial cells. Here we show that basal
      recruitment of TGFbeta receptors occurs subsequent to Hippo-dependent suppression
      of Smad activity by cytoplasmic TAZ/YAP. Our results demonstrate that receptor
      sequestration and Hippo control of activated Smads are distinct events regulating
      TGFbeta signaling in polarized epithelia and raise interesting questions about
      the function of these pathways in controlling Smad signaling in development,
      homeostasis, and disease. This Matters Arising Response addresses the Nallet
      Staub et al. (2015) Matters Arising, published concurrently in Developmental
      Cell. 

PMID- 25758862
TI  - Cell density sensing alters TGF-beta signaling in a cell-type-specific manner,
      independent from Hippo pathway activation.
AB  - Cell-cell contacts inhibit cell growth and proliferation in part by activating
      the Hippo pathway that drives the phosphorylation and nuclear exclusion of the
      transcriptional coactivators YAP and TAZ. Cell density and Hippo signaling have
      also been reported to block transforming growth factor beta (TGF-beta) responses,
      based on the ability of phospho-YAP/TAZ to sequester TGF-beta-activated SMAD
      complexes in the cytoplasm. Herein, we provide evidence that epithelial cell
      polarization interferes with TGF-beta signaling well upstream and independent of
      cytoplasmic YAP/TAZ. Rather, polarized basolateral presentation of TGF-beta
      receptors I and II deprives apically delivered TGF-beta of access to its
      receptors. Basolateral ligand delivery nonetheless remains entirely effective to
      induce TGF-beta responses. These data demonstrate that cell-type-specific
      inhibition of TGF-beta signaling by cell density is restricted to polarized
      epithelial cells and reflects the polarized distribution of TGF-beta receptors,
      which thus affects SMAD activation irrespective of Hippo pathway activation. 

PMID- 25758864
TI  - Surface Control of Epitaxial Manganite Films via Oxygen Pressure.
AB  - The trend to reduce device dimensions demands increasing attention to atomic
      scale details of structure of thin films as well as to pathways to control it.
      This is of special importance in the systems with multiple competing
      interactions. We have used in situ scanning tunneling microscopy to image
      surfaces of La5/8Ca3/8MnO3 films grown by pulsed laser deposition. The atomically
      resolved imaging was combined with in situ angle-resolved X-ray photoelectron
      spectroscopy. We find a strong effect of the background oxygen pressure during
      deposition on structural and chemical features of the film surface. Deposition at
      50 mTorr of O2 leads to mixed-terminated film surfaces, with B-site (MnO2)
      termination being structurally imperfect at the atomic scale. A relatively small
      reduction of the oxygen pressure to 20 mTorr results in a dramatic change of the
      surface structure leading to a nearly perfectly ordered B-site terminated surface
      with only a small fraction of A-site (La,Ca)O termination. This is accompanied,
      however, by surface roughening at a mesoscopic length scale. The results suggest
      that oxygen has a strong link to the adatom mobility during growth. The effect of
      the oxygen pressure on dopant surface segregation is also pronounced: Ca surface
      segregation is decreased with oxygen pressure reduction. 

PMID- 25758866
TI  - Chronic kidney disease in disadvantaged populations.

PMID- 25758865
TI  - The effect of gum chewing on blood GLP-1 concentration in fasted, healthy, non
      obese men.
AB  - We evaluated the effect of chewing on blood GLP-1 concentration by having
      volunteers to chew sugarless gum. Our intention was to explore the neural
      mechanisms regulating the secretion of glucagon-like peptide-1(GLP-1). After
      fasting for 12 h, 12 healthy male, non-obese volunteers (18 < BMI < 30), were
      asked to chew sugarless gum at a frequency of 80 times every 2 min for a total of
      30 min. Blood samples were collected before the start of chewing and 5, 10, 15,
      20, 25, and 30 min after the start of chewing. Satiety and hunger were evaluated
      on a scale from 0 to 100 at each time point. Compared with the control group, the
      test group's satiety was increased at 15, 25, and 30 min (p = 0.043, p = 0.014
      and p = 0.018, respectively) after they began chewing sugarless gum 80 times
      every 2 min. The blood GLP-1 level of the test group at 30 min was 49.6 +/- 20.3
      pmol/l, significantly higher than that of the control group (38.9 +/- 20.9
      pmol/l; p = 0.031). There was no significant difference in the test group's GLP-1
      concentration at each time point. In the control group, compared to baseline, the
      GLP-1 concentrations at 15, 25, and 30 min were significantly decreased (p =
      0.042, p = 0.0214 and p = 0.012, respectively). No significant differences in the
      blood concentration of glucose, insulin and GIP or hunger were observed between
      groups. Our study suggests that fasting sugarless gum chewing can increase
      satiety and reduce the decrease in GLP-1 concentration.

PMID- 25758867
TI  - Albuminuria prediction of kidney function outcome in kidney transplant
      recipients.
AB  - To investigate the association of albuminuria and kidney function outcome in
      kidney transplant recipients, we studied 161 kidney transplant recipients; 95
      (59%) of them were males and the mean age of the patients was 46 +/- 13 years
      (range 18-70 years). All the patients received allografts from living related
      kidney donors. The mean body mass index of the patients was 25 +/- 4 kg/m 2 .
      Forty (25%) patients were diabetic and 72 (45%) patients were hypertensive. All
      the patients had glomerular filtration rate (iGFR) determination by ( 99m Tc
      DTPA) clearance and albumiuria was assessed using the first voided morning urine
      samples. According to the results of albuminuria, the patients were subdivided
      into three groups: One group of 90 (56%) patients with normoalbuminuria (<30 mg
      albumin/g. creatinine), a second group of 52 (32%) patients with microalbuminuria
      (30-300 mg albumin/g. creatinine) and a third group of 19 (12%) patients with
      macroalbuminuria (>300 mg/g. creatinine). There was a significant increase in the
      time post transplantation in the patients with macroalbumiuria in comparison with
      microalbuminuria and normoalbuminuria (90 +/- 28, 60 +/- 22 and 18 +/- 6 months,
      respectively), P <0.05. There was a significant decrease of iGFR in the
      macroalbumiuria group as compared with the microalbumiuria and normoalbuminuria
      groups (57 +/- 24, 74 +/- 20 and 74 +/- 28 mL/min/1.73 m 2 , respectively), P
      <0.05. We conclude that there was an association between albuminuria and the
      status of the renal function in our transplant population, which may reflect
      renal injury due to proteinuria. Prospective studies are warranted to evaluate
      the effect of albuminuria on the prognosis of the kidney allografts. 

PMID- 25758868
TI  - A meta-analysis of potential relationship between Epstein-Barr-Encoded-RNA (EBER)
      and onset time of post-transplant lymphoproliferative disorders.
AB  - Epstein-Barr virus (EBV) encodes two non-polyadenylated RNAs termed EBV-encoded
      RNAs (EBERs). In this study, we tried to find series in which data of EBER and
      onset time of post-transplant lymphoproliferative disorder (PTLD) for patients
      have been documented to conduct a meta-analysis. A comprehensive search of the
      literature was performed by Pubmed and Google scholar to find reports indicating
      test results for EBER and PTLD onset in transplant patients. PTLD was considered
      "early onset" when it develops within the first post-transplant year. Finally,
      265 patients from 15 studies have been included in the meta-analysis. The overall
      meta-analysis also showed a significant relation between EBER test positivity and
      early-onset PTLD development [relative risk (RR): 1.36; 95% CI: 1.16-1.59; P
      <0.001]. The i2 index was 49.8%. Our study suggests that PTLD lesions with
      positive EBER test are more likely to develop within the early post-transplant
      period. Since early-onset PTLD is supposed to have better prognosis, having a
      positive EBER test might not be a bad news. However, for having a precise
      conclusion, prospective studies are needed to be conducted. 

PMID- 25758869
TI  - Comparison of renal function following donor nephrectomy versus radical
      nephrectomy for renal tumor.
AB  - In this study, we compared renal function in patients after donor nephrectomy
      (DN) and radical nephrectomy (RN). We retrospectively reviewed 68 patients (mean
      follow-up 15 months), including 30 patients who had undergone DN and 38 patients
      who had undergone RN. The study was performed between April 2006 and July 2010 at
      a single institute. Patients were matched for age and co-morbidities
      (hypertension and diabetes mellitus). We calculated the estimated glomerular
      filtration rate (eGFR) using the Modification of Diet in Renal Disease study
      group equation. Parameters studied included GFR (>=60 to <60 mL/min/1.73 m 2 ),
      serum creatinine (>2.0 mg/dL), metabolic acidosis (serum bicarbonate <22 mmol/L)
      and proteinuria (>30 mg). There were no significant demographic differences
      between the two study groups. After a mean follow-up of 15 months, low eGFR (<60
      mL/min/1.73 m 2 ) was seen in 28% and 6.7% of patients in the RN and DN groups,
      respectively (P = 0.03). Similarly, proteinuria was seen in 21% vs 0%, P = 0.007,
      and de novo elevated creatinine was seen in 13% vs 0%, respectively P = 0.04;
      thus the changes were greater in the RN group. Our study shows that undergoing RN
      had a significantly greater risk of developing renal insufficiency and
      proteinuria compared with age-and co-morbidity-matched patients undergoing DN. We
      concluded that patients undergoing RN show a significantly greater risk of
      developing renal insufficiency and proteinuria compared with the patients
      undergoing DN. 

PMID- 25758870
TI  - Study of non-compliance among chronic hemodialysis patients and its impact on
      patients' outcomes.
AB  - Non-adherence to prescription is common among hemodialysis (HD) patients and has
      been associated with significant morbidity. At least 50% of HD patients are
      believed to be non-adherent to some part of their treatment. We aimed to assess
      the prevalence of non-adherence to dialysis prescription among 100 chronic HD
      patients. We explored the relationship between non-adherence on one hand and
      socioeconomic profile, depression scores and cognitive function on the other
      hand. The impact of patients' non-adherence on nutritional status, quality of
      life and dialysis adequacy was also assessed. The mean age of the study group was
      50.51 +/- 12.0 years. There were 62 females and 38 males in the study. Thirty-six
      patients (36%) were non-compliant to their dialysis prescription. No significant
      differences were detected between compliant and non-compliant patients in their
      education level and employment status. Inter-dialytic weight gain, serum
      phosphorus and depression scores were significantly higher in non-compliant
      patients compared with compliant patients, whereas body weight, serum albumin,
      serum calcium, quality of life scores and nutrition scores were significantly
      higher in compliant patients (P <0.05). In conclusion, non-adherence is highly
      prevalent among chronic HD patients and is associated with poor quality of life,
      depression and malnutrition. 

PMID- 25758871
TI  - Nutritional knowledge following interventional educational sessions in children
      on regular hemodialysis.
AB  - To evaluate the impact of nutritional knowledge following interventional
      educational sessions in chronic dialysis patients, we studied 40 children on
      chronic regular hemodialysis (HD) at the beginning and after six months of
      nutrition educational sessions using a predesigned questionnaire. We also
      measured the anthropometric parameters of nutrition to evaluate the impact of
      this education on the health of patients. We found a highly statistically
      significant increase in patients' scores and in adequate knowledge using the
      questionnaire after the educational sessions. Our results showed a statistically
      significant decrease in body mass index and weight after educational sessions for
      six months. Moreover, there were no significant decreases in serum phosphorus,
      ferritin, iron and creatinine, in contrast with no significant increase in
      hemoglobin, serum calcium, blood urea nitrogen and serum albumin. We conclude
      that nutritional education is significantly effective with regard to the level of
      knowledge, but not with regard to the attitude and practice in children on
      chronic HD. 

PMID- 25758872
TI  - Coping methods to stress among patients on hemodialysis and peritoneal dialysis.
AB  - Dialysis patients need to deal and cope with various aspects of their disease.
      Identifying the adaptation methods provides valuable information for planning
      specific treatment and medical care delivery and improving the performance of
      medical teams. The present study aims to evaluate the coping strategies to stress
      among patients undergoing hemodialysis (HD) and peritoneal dialysis (PD) at the
      Imam Reza Educational-Medical Hospital, Tabriz, West Azarbaijan, Iran. This
      descriptive and analytical study was conducted on 70 patients in the year 2012.
      The subjects were selected through census method and simple random sampling
      method. Data were collected using a customized questionnaire and consisted of
      demographic information and the Jalowiec Coping Scale (JCS) through a structured
      interview. Descriptive and inferential statistics were used to analyze the data
      in SPSS (version 13). The mean score of frequency of use of the coping strategy
      as "sometimes used" for the HD patients was 70.94 +/- 18.91 and also for PD
      patients as "seldom used" was 58.70 +/- 12.66. The mean score of helpfulness of
      coping strategies in the HD group was 49.57 +/- 19.42 as "slightly helpful",
      whereas in the PD group it was 37.21 +/- 14.38 as "slightly helpful" Furthermore,
      both groups used the emotion-oriented coping styles more frequently than the
      problem-oriented methods. HD patients used coping methods more frequently than
      the PD patients. The majority of patients used emotion-oriented coping strategies
      to deal with stress factors. Use of educational, counseling and supportive
      programs to assist in coping techniques can facilitate the coping process with
      stress factors in dialysis patients. 

PMID- 25758873
TI  - The effect of regular hemodialysis on the nutritional status of children with end
      stage renal disease.
AB  - Growth failure is one of the most common and profound clinical manifestation of
      chronic kidney disease (CKD) in infants, children and adolescents. The aim of
      this study was to assess the nutritional status of Egyptian children with end
      stage renal disease (ESRD) on regular hemodialysis (HD). The study included 50
      Egyptian children with ESRD on regular HD, following-up at the Pediatric
      Nephrology unit, Cairo University. History, including dietary history, was taken
      for all patients and clinical examination was performed on all of them. Body
      weight, standing height, height or length SD score, the skin fold thickness, mid
      arm circumference, mid-arm muscle circumference and mid-arm muscle circumference
      area were also assessed. The height of the patients was the most affected
      anthropometric parameter, as 78% of the patients were shorter (height SDS below 
      3). Body weight is less affected than height, as body weight SDS of 34% of
      patients was less than -3 SDS. In addition, the body mass index of 16% of the
      patients was <3 rd percentile, while only 4% of the patients were >97 th
      percentile. Although most ESRD patients received adequate protein and caloric
      intake, their growth was markedly affected, especially with longer period on HD.
      We suggest that assessment of growth parameters should be performed at a minimum
      period of every six months in children with CKD stages 2-3. For children with
      more advanced CKD (stages 4-5 and 5D), more frequent evaluation may be warranted
      due to the greater risk of abnormalities. 

PMID- 25758874
TI  - Gabapentin versus levodopa-c for the treatment of restless legs syndrome in
      hemodialysis patients: a randomized clinical trial.
AB  - To compare the efficacy of gabapentin and levodopa-c (Levodopa/Carbidopa) in
      reducing restless leg syndrome (RLS) symptoms and sleep problems in hemodialysis
      patients with RLS in a four-week randomized clinical trial. The diagnosis of RLS
      was made using the criteria of the International Restless Legs Study Group. Each
      subject completed three questionnaires: IRLS questionnaire, Pittsburgh Sleep
      Quality Index and Epworth sleepiness scale. After four weeks of washout period
      for previous treatments for RLS, subjects were randomly assigned to four weeks of
      gabapentin (200 mg) or levodopa-c (110 mg). After four weeks of therapy, the
      questionnaires administered at the outset of the study were re-administered. Both
      drugs were found effective for the management of RLS. But, the effect of
      gabapentin was more significant. Gabapentin significantly improved the IRLS total
      score (change from baseline to post-treatment ~-17) compared with levodopa-c
      (change from baseline to post-treatment ~-13) (P: 0.016). Regarding sleep
      parameters, levodopa improved sleep quality, sleep latency and sleep duration (P
      <0.0001). Gabapentin was also effective with respect to sleep parameters (P
      <0.0001). Our study shows that gabapentin is a safe effective therapy for RLS
      among hemodialysis patients. This medication may be considered as an alternative
      or additive treatment to current therapeutic remedies for hemodialysis patients
      with RLS. 

PMID- 25758875
TI  - Diagnostic value of color doppler ultrasonography in detecting stenosis and
      occlusion of central veins in patients with chronic kidney disease.
AB  - Venography is an invasive diagnostic test that uses contrast material that
      provides a picture of the condition of the veins. But, complications, including
      adverse effects on the kidney, do occur. On the other hand, with the current
      technological development, application of ultrasound in the diagnosis of
      obstructive diseases of the veins is gaining popularity, being non-invasive, easy
      to perform and cost-effective. The aim of this study was to evaluate the
      diagnostic value of Doppler sonography in the diagnosis of central vein stenosis.
      In this descriptive-analytical study, 41 hemodialysis patients who had been
      referred for 50 upper limb venographies to the radiology department of Imam Reza
      (AS) were included. Patients with chronic kidney disease with a history of
      catheterization of the vein, jugular or subclavian, and who had established
      fistulas or synthetic vascular grafts were targeted. Central venous ultrasound
      was performed on both sides to evaluate stenosis or occlusion. Venography was
      performed by the radiologist the next day or the day before hemodialysis. Data on
      demographic characteristics, findings of clinical examination and findings of
      ultrasound as well as venography were recorded by using the SPSS software, Chi
      square test and Spearman correlation, and Kappa agreement was calculated for
      sensitivity, specificity and predictive values. Twenty-three (56%) patients were
      male subjects and 18 patients (44%) were female. Twenty-three (56%) patients of
      the study population were aged <60 years and 18 (43/9%) patients were aged >60
      years. The overall sensitivity, specificity and positive predictive value and
      negative predictive value of Doppler sonography in the proximal veins in
      hemodialysis patients compared with venography were, respectively, 80.9%, 79.3%,
      73.9% and 85.1%. Color Doppler sonography, as a non-invasive method, could be a
      good alternative for venography in the assessment of the upper limb with central
      vein stenosis and occlusion. 

PMID- 25758876
TI  - The impact of pediatric nephrotic syndrome on parents' health-related quality of
      life and family functioning: an assessment made by the PedsQL 4.0 family impact
      module.
AB  - The multi-dimensional impact on the quality of life (QOL) of families of children
      with the nephrotic syndrome (NS) has not been studied sufficiently in the
      literature. We aimed to study this aspect and the predictors of poor QOL among
      Indian families having children with NS. A cross-sectional study was conducted to
      compare the parents of children with chronic NS on treatment for at least one
      year with parents of a matched healthy control group. The parents of both groups
      were asked to complete the standard self-administered multi-dimensional
      questionnaire of Pediatric Quality of Life Inventory 4 (PedsQL TM ) Family Impact
      Module (FIM). Descriptive and analytical statistics were performed to compare
      scores between the two groups. Possible predictors of poor outcome in each of the
      summary scales among the cases were assessed by both univariate and multivariate
      analysis. The parents of 61 cases and 72 controls completed the PedsQL TM FIM
      questionnaire. The scores in each of the categories, namely FIM Total Scale
      Score, Parent HRQOL Summary Score, Family Functioning Summary Score and eight
      individual domains, were found to be significantly higher among controls. Female
      gender of the affected child was an independent risk factor for poor Family
      Functioning Summary Score. Also, presence of serious complications during the
      course of the disease independently predicted poor Total FIM and Parent HRQOL
      Summary Scores. Even a relatively benign and potentially curable chronic disorder
      in children, like the NS, can disturb the QOL of parents in multiple domains of
      functioning. 

PMID- 25758877
TI  - Comparison of measured glomerular filtration rates with isotope infusion and with
      the modification of diet in renal disease equation in cancer patients with raised
      serum creatinine.
AB  - To compare the measured glomerular filtration rate (rGFR) using [99mTc]
      diethylene triamine pentacetic acid (DTPA) clearance or estimated GFR (eGFR) by
      the Modification of Diet in Renal Disease (MDRD) equation in cancer patients with
      raised serum creatinine level, we studied 100 cancer patients; 50 patients with
      normal serum creatinine (control group) and 50 patients with abnormal serum
      creatinine (study group). History of patients, including site of cancer,
      chemotherapy regime and dose of chemotherapy, was recorded. The rGFR and eGFR
      were increased in the study group as compared with the control group, but the GFR
      recorded by the MDRD formula or DTPA revealed similar values. It is therefore
      concluded that the MDRD equation may be recommended for eGFR estimation even with
      abnormal creatinine, without the need for exposure to radiation. 

PMID- 25758878
TI  - Non-tolerability of double-filtration plasmapheresis in antibody-incompatible
      kidney transplant candidates.
AB  - Few studies have reported the use of double-filtration plasmapheresis (DFPP) in
      antibody-incompatible kidney transplantation. To assess the efficiency and
      tolerability of DFPP, we prospectively studied four chronic hemodialysis patients
      from two centers undergoing antibody-incompatible kidney transplantation. DFPP
      was used for ABO-incompatible transplantation (n = 1), for high human leukocyte
      antigen (HLA) immunization levels (n = 2) or for the presence of a donor-specific
      antibody (DSA) against a potential living donor (n = 1). In all the patients, the
      DFPP program was discontinued because of the adverse effects. Low blood pressure
      occurred during the first hour of the session in all the patients. A significant
      loss of plasma proteins, clotting factors and immunoglobulins also occurred
      during this treatment. In addition, fistula thrombosis was diagnosed in two
      patients. Three patients experienced gastrointestinal symptoms. The DFPP reduced
      the titers of the anti-B antibodies and reduced the levels of DSA in one patient,
      but had no effect on anti-HLA antibodies in the remaining two patients. Our study
      highlights the non-tolerability and poor efficacy of DFPP prior to antibody
      incompatible kidney transplantation that limit its extensive use in the
      desensitization protocols. 

PMID- 25758879
TI  - Geriatric nutritional risk index: a mortality predictor in hemodialysis patients.
AB  - Recently, the Geriatric Nutritional Risk Index (GNRI) has been introduced as a
      valuable tool to assess the nutritional status of hemodialysis (HD) patients. To
      determine the predictive value of the GNRI score for death in HD, we studied 145
      chronic HD patients (%53 men, mean age 60 +/- 16 years). The GNRI score was
      estimated by an equation involving serum albumin and individual's weight and
      height. According to the highest positive likelihood and risk ratios, the cut-off
      value of the GNRI for mortality was set at 100. The survival of patients on HD
      was examined with the Cox proportional hazards model. Mortality was monitored
      prospectively over an 18-month period, during which 35 patients died. The GNRI
      (mean 102.6 +/- 5.5) was significantly positively correlated with lean body mass,
      hematocrit, serum lipids and presence of metabolic syndrome. Multivariate Cox
      proportional hazards analysis demonstrated that the GNRI <100, serum ferritin >=
      500 MU g/L and age 65 years or older were significant predictors for mortality
      (hazard ratio 3.691, 95% CI 1.751-7.779, P = 0.001; hazard ratio 3.105, 95% CI
      1.536-6.277, P = 0.002; and hazard ratio 2.806, 95% CI 1.297-6.073, P = 0.009,
      respectively), after adjustment to gender and vintage time. It can be concluded
      that, in addition to old age, malnutrition (low GNRI) and inflammation (high
      ferritin) are identified as significant independent risk factors that predict all
      cause mortality in HD patients. 

PMID- 25758880
TI  - Continuous ambulatory peritoneal dialysis: nurses' experiences of teaching
      patients.
AB  - Nine nurses were interviewed to determine nurses' experiences of teaching
      patients to use continuous ambulatory peritoneal dialysis (CAPD). The material
      was analyzed using content analysis. Data were sorted into four themes and ten
      subthemes. The themes were presented as follows: Importance of language,
      individualized teaching, teaching needs and structure of care in teaching. The
      findings highlighted important insights into how nurses experience teaching
      patients to perform CAPD. The study revealed some barriers for the nurses during
      teaching. The major barrier was shortage of Arabic speaking nursing staff.
      Incidental findings involved two factors that played an important role in
      teaching, retraining and a special team to perform pre-assessments, including
      home visits. In conclusion, the findings of this study showed several factors
      that are considered as barriers for the nurses during teaching the CAPD patients
      and the need to improve the communication and teaching in the peritoneal dialysis
      units, including the importance of individualized teaching. 

PMID- 25758881
TI  - Pediatric systemic lupus erythematosus in a single nephrology unit.
AB  - Clinical manifestations of systemic lupus erythematosus (SLE) are widely
      variable, and its course is unpredictable. SLE that begins in childhood has been
      considered more severe than SLE with onset during adulthood. Our aim was to
      determine the presentation and the outcome of SLE of 26 children (20 females and
      6 males, with a female to male ratio of 3.8:1) with SLE in our center, their ages
      ranging from 5 - 18 years and followed from 2005 till October 2011. They were
      diagnosed according to the American Rheumatism Association's revised criteria.
      Complete blood count, erythrocyte sedimentation rate, C3, urine analysis, 24-h
      urinary protein, antinuclear antibodies, anti-ds DNA and renal biopsy were
      obtained for the patients. We found that the most extra-renal manifestation of
      SLE was fever (57.7%), while lupus nephritis (LN) was the most commonly affected
      organ (50%). Hemolytic anemia was the most common hematological abnormality
      (80.8%), while immunological characteristics were positive in all the patients.
      Remission in patients without LN was more than 5.3-times the remission in LN
      patients. The outcome of the patients without LN was better than the patients
      with LN. 

PMID- 25758882
TI  - Effects of fasting during Ramadan on renal function of patients with chronic
      kidney disease.
AB  - Fasting during Ramadan is prohibited when an individual's health is endangered.
      Little work has been published in this direction in patients with chronic kidney
      disease (CKD). We aimed to evaluate the impact of fasting during Ramadan on the
      renal function of patients with CKD, adjusting for the initial degree of renal
      impairment. We prospectively studied 60 patients with CKD (35 females; mean age
      45.6 +/- 15.8 years). All study patients were older than 15 years, being followed
      up at the nephrology clinic for more than six months, having a stable CKD during
      the preceding six months and who had fasted during Ramadan the previous year.
      Patients who had a medical contra-indication for fasting were excluded from the
      study [severe or resistant arterial hypertension, insulin-requiring diabetes,
      acute renal failure (ARF), active renal disease, repetitive urolithiasis or
      terminal chronic renal failure]. Statistical analysis was performed in
      collaboration with the epidemiology lab at the Fez Medical School using the SPSS
      software version 17. Three of the study patients developed ARF in the first week
      and four of them at the end of the month of the study period. The risk of
      developing ARF was significantly higher for patients with baseline creatinine
      clearance of <60 mL/min/1.73 m 2 . However, the small sample size does not allow
      us to draw any firm conclusions on fasting during Ramadan in stable CKD patients.
      Studies on larger numbers of patients are recommended. 

PMID- 25758883
TI  - Metformin-associated lactic acidosis in a peritoneal dialysis patient.
AB  - Metformin is one of the commonly used drugs in type-2 diabetes mellitus. It
      reduces glucose levels by increasing insulin sensitivity, reducing hepatic
      glucose release and increasing muscle uptake. One of the serious complications
      associated with metformin use is lactic acidosis, and it is associated with high
      morbidity and mortality. This is more likely to happen in patients with renal
      failure due to reduced clearance. International guidelines recommend
      discontinuing metformin in advanced renal failure. We report a case of metformin
      associated lactic acidosis in a patient with end-stage renal disease on
      peritoneal dialysis. The patient presented with severe lactic acidosis, which was
      successfully treated with hemodialysis. 

PMID- 25758884
TI  - Encapsulating peritoneal sclerosis: presentation without preceding symptoms.
AB  - Encapsulating peritoneal sclerosis (EPS) is a rare but devastating complication
      of peritoneal dialysis (PD), resulting in malnutrition and ultimately overt
      intestinal obstruction. We present the case of a 71-year-old man diagnosed with
      EPS incidentally at laparotomy for removal of PD catheter following an episode of
      PD peritonitis. He had been treated with continuous ambulatory PD for 18 months.
      He presented with anasarca and did not exhibit persistent symptoms of
      gastrointestinal dysfunction to suggest the EPS. Computed tomography scanning
      obtained 18 days prior to confirmation of the diagnosis did not demonstrate any
      features suggestive of EPS, highlighting a deficiency in the sensitivity of the
      diagnostic investigations. Management of the EPS is typically complicated by late
      diagnosis and concomitant malnutrition. This case highlights both the insidious
      nature of the EPS and a management problem to the surgeon faced with an
      unexpected abdominal cocoon. It further accentuates the necessity for
      increasingly sensitive diagnostic investigations to allow earlier diagnosis,
      thereby facilitating successful treatment. 

PMID- 25758885
TI  - Spontaneous peri-nephric hematoma in a patient with acute kidney injury following
      Russell's viper envenomation.
AB  - Snake bite envenomation is a common cause of acute kidney injury (AKI) in the
      tropics and severe coagulopathy with bleeding manifestations is usually seen,
      especially with viperine bites. We present a case of a 34-year-old male who had
      developed AKI following Russell's viper envenomation along with disseminated
      intravascular coagulation. The patient was seemingly improving during the course
      of his treatment but subsequently developed a spontaneous unilateral peri-nephric
      hematoma and finally succumbed to this complication. This is a rare presentation
      that can be clinically innoccuous in a disease where there are multiple bleeding
      manifestations and, carries a very poor outcome. 

PMID- 25758886
TI  - Visceral phaeohyphomycosis caused by Alternaria alternata offering a diagnostic
      as well as a therapeutic challenge.
AB  - Phaeohyphomycosis is a heterogeneous group of opportunistic infections caused by
      dematiaceous molds, which are distributed worldwide as plant pathogens but rarely
      cause human diseases. However, due to the growing populations of
      immunocompromised patients, these fungi are frequently recognized as important
      human pathogens. We are reporting this very rare, unique case for the first time
      from Islamabad, Pakistan, describing the association of visceral
      Phaeohyphomycosis caused by the opportunistic fungus Alternaria alternata,
      affecting the left kidney, with the immunocompromised state in a young
      incidentally detected patient with insulin-dependent type I diabetes. The case
      was diagnosed on the basis of a high index of clinical suspicion, microbial
      cultures, microscopy, imaging studies and endourological procedures. The patient
      did not respond well to the highly sensitive Amphotericin B, resulting in loss of
      the kidney. Therefore, we suggest that clinicians involved in treating
      immunocompromised patients should have a high degree of clinical suspicion for
      such opportunistic pathogens to allow timely initiation of the correct diagnostic
      and therapeutic work-up. 

PMID- 25758887
TI  - Multiple sites of calciphylaxis in a patient with chronic renal failure.
AB  - Calciphylaxis has seldom been reported in patients with acute renal failure or in
      pre-dialysis patients. It also has been reported at lower calcium phosphorous
      products and in patients with adynamic bone disease. We report a pre-hemodialysis
      (HD) patient with acute renal failure and biopsy-proven calciphylaxis involving
      multiple cutaneous sites with calcification of the perineal area resulting in dry
      gangrene of the penis that necessitated a partial penectomy. The patient had
      elevated serum calcium, phosphorous and parathyroid hormone level of 612 pg/mL.
      The same patient suffered subsequently from a calcium embolus that occluded his
      left ophthalmic artery and resulted in left eye blindness. Calciphylaxis is a
      devastating phenomenon and physicians should have a high clinical suspicion for
      it in HD patients as well as in patients with late stages of chronic kidney
      disease. 

PMID- 25758888
TI  - Intrathoracic kidney in a child with literature review.
AB  - Intrathoracic kidney (ITK) is an extremely rare congenital anomaly, often
      asymptomatic and discovered incidentally on chest radiography. Diagnosis in
      children is less frequent than in adults. It affects males more than females and
      is more common on the left side. Symptoms can be present if it is associated with
      diaphragmatic defect, herniation of abdominal contents or respiratory compromise.
      We report a case of a three-year-old boy with right ITK, diagnosed incidentally
      by chest radiography during treatment of lower respiratory tract infection and
      confirmed by chest computerized tomography scan. 

PMID- 25758889
TI  - An unusual presentation of venous thrombosis in a child with idiopathic
      membranous nephropathy.
AB  - Venous thrombosis is one of the major complications associated with nephrotic
      syndrome. Among the primary glomerular diseases, membranous nephropathy is
      associated with a high incidence of thrombotic events. Although this is well
      described in adults, there is paucity of the literature regarding venous
      thrombosis in children. Herein, we report such a thrombotic event involving both
      the lower limb veins and the inferior vena cava in a child with membranous
      nephropathy. 

PMID- 25758890
TI  - Microscopic polyangiitis associated with primary biliary cirrhosis, Sjogren's
      syndrome and Hashimoto's thyroiditis.
AB  - The association between microscopic polyangiitis (MPA) and primary biliary
      cirrhosis (PBC) has seldom been reported. We describe here a patient who
      presented with sensorimotor neuropathy along with hypothyroidism, renal failure
      and liver dysfunction. Detection of antinuclear antibodies at a titer of 1/800,
      anti-SSA, anti-SSB, anti-GP210, anti-microsomial and p-ANCA anti-myeloperoxydase
      antibodies along with renal, salivary and liver biopsy led to a diagnosis of MPA
      associated with PBC, Sjogren's syndrome and Hashimoto's thyroiditis. 

PMID- 25758891
TI  - The efficacy of dipyridamole in the treatment of hypophosphatemia- hypocalcemia
      for hungry bone syndrome in a hemodialysis patient.

PMID- 25758892
TI  - A patient with hemodialysis intolerance and hypereosinophilia.

PMID- 25758893
TI  - Occult hepatitis C virus infection in dialysis patients: does it need special
      attention?

PMID- 25758894
TI  - The effect of serum fetuin-A on atherosclerosis in hemodialysis patients.

PMID- 25758895
TI  - Occurrence of microalbuminuria among children and adolescents with insulin
      dependent diabetes mellitus.

PMID- 25758896
TI  - Age and gender distribution of primary and secondary glomerulonephritis obtained
      by renal biopsy: a study from Hamadan, a great province in Western Iran.

PMID- 25758897
TI  - Sleep quality and C-reactive protein.

PMID- 25758898
TI  - Prevalence and associated factors of hepatitis C virus infection among renal
      disease patients on maintenance hemodialysis in three health centers in Aden,
      Yemen: a cross sectional study.
AB  - We aimed to assess the prevalence and factors associated with positive anti
      hepatitis C virus (HCV) antibodies among patients on maintenance hemodialysis
      (HD) in three centers in Aden, Yemen. The data from 219 patients and their
      records over the period between 2000-2013, was extracted and analyzed. The mean
      +/- SD age of the patients was 47.08 +/- 13.9 years; 74.4% of them were married
      and 14.6% were employed. The prevalence of validated anti-HCV-positive cases was
      40.2% (95%CI 33.64%-46.73%). The mean +/- SD duration on HD of all the patients
      was 35.09 +/- 38 months. On bivariate analysis, the duration on HD and attending
      more than one center for HD associated significantly with anti-HCV positivity (P
      <0.05). On multivariate fully adjusted Poisson regression modelling, controlled
      for age, Patients attending more than one center and those who underwent HD for
      longer durations were more likely to be positive for anti- HCV antibodies [P =
      0.004, adjusted prevalence rate ratio (APRR) = 1.87, 95% confidence interval
      (CI): 1.22-2.88; P = 0.0005, APRR = 1.01, 95% CI: 1.00-1.02. In this study
      sample, the prevalence of HCV was significant. Patients attending more than one
      center and those who underwent HD for longer durations were found to be more
      likely to contract HCV. Enhancing existing infection control measures and
      allocating more resources to HD centers therefore warrants consideration. 

PMID- 25758899
TI  - Epidemiology of urolithiasis with emphasis on ultrasound detection: a
      retrospective analysis of 5371 cases in Saudi Arabia.
AB  - This retrospective study was conducted to determine the prevalence of urinary
      calculi in the indigenous population of Saudi Arabia and compare it with
      expatriates of different nationalities working in Saudi Arabia with emphasis on
      the anatomic location of the calculi and the role of ultrasound in the detection
      and management. The study included 5371 patients (both sexes, mean age 36.6
      years) examined by us from September 2004 to February 2008. The patients hailed
      from 30 countries, which included Bangladesh (42.3%), Pakistan (18.3%), Yemen
      (17.5%), India (6.5%), Sudan (3.4%), Saudi Arabia (2.8%), Egypt (2.3%) and
      Eritrea (1.7%). All patients were referred for abdominal/renal ultrasonography.
      Urinary calculi were detected in 1029 patients. The distribution of calculi was
      as follows: Renal 73.3%, pelviureteric junction 2.3%, proximal, middle and distal
      thirds of the ureter 13%, vesicouretic junction 9.8%, vesical 1.1% and urethral
      0.5%. The prevalence of urinary calculi according to ethnic origin in descending
      order of frequency was Egyptians (29.5%), Pakistani (24.9%), Indian
      (23.3%),Yemeni (20.5%), Sudanese (17.6%), Bangladeshi (16.2%), Eritrean (15.4%)
      and Saudi Arabian (7.4%). Urinary calculi were found in 19.1% of the studied
      population. Approximately three-quarters of the calculi were located within the
      kidney. The nationalities with the highest prevalences were Egyptian, Pakistani
      and Indian. 

PMID- 25758900
TI  - Comparison of survival in patients with end-stage renal disease receiving
      hemodialysis versus peritoneal dialysis.
AB  - Although the life expectancy of patients with end-stage renal disease (ESRD) has
      improved in recent years, it is still far below that of the general population.
      In this retrospective study, we compared the survival of patients with ESRD
      receiving hemodialysis (HD) versus those on peritoneal dialysis (PD). The study
      was conducted on patients referred to the HD and PD centers of the Emam Khomini
      Hospital and the Aboozar Children's Hospital from January 2007 to May 2012 in
      Ahvaz, Iran. All ESRD patients on maintenance HD or PD for more than two months
      were included in the study. The survival was estimated by the Kaplan-Meier method
      and the differences between HD and PD patients were tested by the log-rank test.
      Overall, 239 patients, 148 patients on HD (61.92%) and 91 patients on continuous
      ambulatory PD (CAPD) (38.55%) with mean age of 54.1 +/- 17 years were enrolled in
      the study. Regardless of the causes of ESRD and type of renal replacement therapy
      (RRT), one-, two- and three-year survival of patients was 65%, 51% and 35%,
      respectively. There was no significant difference between type of RRT in one- (P
      value = 0.737), two- (P-value = 0.534) and three- (P-value = 0.867) year
      survival. There was also no significant difference between diabetic and non
      diabetic patients under HD and CAPD in the one-, two- and three-year survival.
      Although the three-year survival of diabetic patients under CAPD was lower than
      that of non-diabetic patients (13% vs. 34%), it was not statistically significant
      (P-value = 0.50). According to the results of the current study, there is no
      survival advantage of PD during the first years of initiation of dialysis, and
      the one-, two- and three-year survival of HD and PD patients is also similar. 

PMID- 25758901
TI  - C1q nephropathy in India: a single-center study.
AB  - C1q nephropathy (C1qN) is defined by conspicuous C1q deposits in the glomerular
      mesangial regions of patients who do not have any evidence of systemic lupus
      erythematosus (SLE). We present our experience with C1qN over the last three
      years. In total, 1775 native renal biopsies were reviewed and dominant/co
      dominant C1q mesangial deposits in patients with absence of clinical and/or
      serological evidence of SLE were considered as C1qN. Their clinical profile and
      renal function status were studied and correlated. C1qN was observed in 11
      patients (0.61%), and included eight males and three females; the mean age was
      36.6 years. The most common presentation was nephrotic syndrome. Hematuria was
      noted in eight patients (72%). The mean serum creatinine was 2.78 mg/dL.
      Hypertension was seen in two patients (18%). Mesangial proliferative
      glomerulonephritis (MePGN) was the most common histological pattern, followed by
      focal and segmental glomerulosclerosis and other lesions. The common codeposits
      along with C1q were IgM, followed by C3 and others. MePGN had better prognosis
      than others. To conclude, C1qN was noted in 0.61% of all renal biopsies with
      bimodal age distribution and may present as podocytopathy or non-podocytopathy.
      The prognosis depends on the morphological pattern and C1q deposits per se are
      not prognostic indicators. 

PMID- 25758902
TI  - Poorly differentiated neoplasms of unknown primary site: diagnostic usefulness of
      a molecular cancer classifier assay.
AB  - PURPOSE: Definition of the lineage of poorly differentiated neoplasms (PDNs)
      presenting as cancer of unknown primary site (CUP) is important since many of
      these tumors are treatment-sensitive. Gene expression profiling and a molecular
      cancer classifier assay (MCCA) may provide a new method of diagnosis when
      standard pathologic evaluation and immunohistochemical (IHC) staining is
      unsuccessful. PATIENTS AND METHODS: Thirty of 751 CUP patients (4%) seen from
      2000-2012 had PDNs without a definitive lineage diagnosed by histology or IHC
      (median 18 stains, range 9-46). Biopsies from these 30 patients had MCCA (92-gene
      reverse transcriptase-polymerase chain reaction mRNA) performed. Additional IHC,
      gene sequencing, fluorescent in situ hybridization for specific genetic
      alterations, and repeat biopsies were performed to support MCCA diagnoses, and
      clinical features correlated. Seven patients had MCCA performed initially and
      received site-specific therapy. RESULTS: Lineage diagnoses were made by MCCA in
      25 of 30 (83 %) patients, including ten carcinomas (three germ cell, two
      neuroendocrine, five others), eight sarcomas [three peritoneal mesotheliomas, one
      primitive neuroectodermal tumor (PNET), four others], five melanomas, and two
      lymphomas. Additional IHC and genetic testing [BRAF, i(12)p] supported the MCCA
      diagnoses in 11 of 16 tumors. All seven patients (two germ cell, two
      neuroendocrine, two mesothelioma, one lymphoma) responded to site-specific
      therapy based on the MCCA diagnosis, and remain alive (five progression-free)
      from 25+ to 72+ months. CONCLUSION: The MCCA provided a specific lineage
      diagnosis and tissue of origin in most patients with PDNs unclassifiable by
      standard pathologic evaluation. Earlier use of MCCA will expedite diagnosis and
      direct appropriate first-line therapy, which is potentially curative for several
      of these tumor types.

PMID- 25758903
TI  - BRAF(V600E) mutations are found in Richter syndrome and may allow targeted
      therapy in a subset of patients.

PMID- 25758906
TI  - Abstracts of the Diabetes UK Professional Conference 2015, 11-13 March, 2015,
      London, England .

PMID- 25758905
TI  - Replicated linear association between DUF1220 copy number and severity of social
      impairment in autism.
AB  - Sequences encoding DUF1220 protein domains exhibit an exceptional human-specific
      increase in copy number and have been associated with several phenotypes related
      to brain size. Autism is a highly heritable and heterogeneous condition
      characterized behaviorally by social and communicative impairments, and increased
      repetitive and stereotyped behavior. Given the accelerated brain growth pattern
      observed in many individuals with autism, and the association between DUF1220
      subtype CON1 copy number and brain size, we previously investigated associations
      between CON1 copy number and autism-related symptoms. We determined that CON1
      copy number increase is associated with increasing severity of all three
      behavioral features of autism. The present study sought to replicate these
      findings in an independent population (N = 166). Our results demonstrate a
      replication of the linear relationship between CON1 copy number and the severity
      of social impairment in individuals with autism as measured by Autism Diagnostic
      Interview-Revised Social Diagnostic Score, such that with each additional copy of
      CON1 Social Diagnostic Score increased 0.24 points (SE = 0.11, p = 0.036). We
      also identified an analogous trend between CON1 copy number and Communicative
      Diagnostic Score, but did not replicate the relationship between CON1 copy number
      and Repetitive Behavior Diagnostic Score. Interestingly, these associations
      appear to be most pronounced in multiplex children. These results, representing
      the first replication of a gene dosage relationship with the severity of a
      primary symptom of autism, lend further support to the possibility that the same
      protein domain family implicated in the evolutionary expansion of the human brain
      may also be involved in autism severity.

PMID- 25758908
TI  - Factors influencing the life cycle burdens of the recovery of energy from
      residual municipal waste.
AB  - A life cycle assessment was carried out to assess a selection of the factors
      influencing the environmental impacts and benefits of incinerating the fraction
      of municipal waste remaining after source-separation for reuse, recycling,
      composting or anaerobic digestion. The factors investigated were the extent of
      any metal and aggregate recovery from the bottom ash, the thermal efficiency of
      the process, and the conventional fuel for electricity generation displaced by
      the power generated. The results demonstrate that incineration has significant
      advantages over landfill with lower impacts from climate change, resource
      depletion, acidification, eutrophication human toxicity and aquatic ecotoxicity.
      To maximise the benefits of energy recovery, metals, particularly aluminium,
      should be reclaimed from the residual bottom ash and the energy recovery stage of
      the process should be as efficient as possible. The overall environmental
      benefits/burdens of energy from waste also strongly depend on the source of the
      power displaced by the energy from waste, with coal giving the greatest benefits
      and combined cycle turbines fuelled by natural gas the lowest of those
      considered. Regardless of the conventional power displaced incineration presents
      a lower environmental burden than landfill. 

PMID- 25758904
TI  - Delving into the complexity of hereditary spastic paraplegias: how unexpected
      phenotypes and inheritance modes are revolutionizing their nosology.
AB  - Hereditary spastic paraplegias (HSP) are rare neurodegenerative diseases sharing
      the degeneration of the corticospinal tracts as the main pathological
      characteristic. They are considered one of the most heterogeneous neurological
      disorders. All modes of inheritance have been described for the 84 different loci
      and 67 known causative genes implicated up to now. Recent advances in molecular
      genetics have revealed clinico-genetic heterogeneity of these disorders including
      their clinical and genetic overlap with other diseases of the nervous system. The
      systematic analysis of a large set of genes, including exome sequencing, is
      unmasking unusual phenotypes or inheritance modes associated with mutations in
      HSP genes and related genes involved in various neurological diseases. A new
      nosology may emerge after integration and understanding of these new data to
      replace the current classification. Collectively, functions of the known genes
      implicate the disturbance of intracellular membrane dynamics and trafficking as
      the consequence of alterations of cytoskeletal dynamics, lipid metabolism and
      organelle structures, which represent in fact a relatively small number of
      cellular processes that could help to find common curative approaches, which are
      still lacking. 

PMID- 25758909
TI  - Investigation of degree of saturation in landfill liners using electrical
      resistivity imaging.
AB  - During construction of compacted clay liners and evapotranspiration (ET) covers,
      quality control involves laboratory and field tests in individual lifts. However,
      the available methods may be inadequate to determine non-uniform compaction
      conditions, poor bonding of lifts, and/or variable soil composition. Moreover,
      the applicability of the available methods is restricted, in many instances, when
      spatial variability of the subsurface is expected. Resistivity Imaging (RI) is a
      geophysical method employed to investigate a large area in a rapid and non
      destructive way. High resistivity of clay liner soil is an indication of a low
      degree of saturation, high air-filled voids, and poor lift bonding. To utilize RI
      as a quality control tool in a landfill liner, it is important to determine the
      saturation condition of the compacted soils because compaction and permeability
      of liner soil are functions of degrees of saturation. The objective of the
      present study is to evaluate the degree of saturation of a municipal solid waste
      (MSW) landfill liner, using RI. Electrical resistivity tests were performed in
      the laboratory, at varied moisture contents and dry unit weights, on four types
      of soil samples, i.e., highly plastic clay (CH), low plastic clay (CL), Ca
      bentonite, and kaolinite. According to the experimental results, electrical
      resistivity of the specimens decreased as much as 15.3 times of initial value
      with increase in the degrees of saturation from 23% to 100%. In addition, cation
      exchange capacity (CEC) substantially affected resistivity. A multiple linear
      regression (MLR) model was developed to correlate electrical resistivity with
      degree of saturation and CEC using experimental results. Additionally, RI tests
      were conducted on compacted clay liners to determine the degrees of saturation,
      and predicted degrees of saturation were compared with the in-situ density tests.
      The study results indicated that the developed model can be utilized for liner
      soils having CEC, resistivity and degrees of saturation between 13.3 and
      79cmol+/kg, and 2.6 and 504.3Ohmm, and 21.8% to 100%; respectively. 

PMID- 25758910
TI  - Atomic interaction mechanism for designing the interface of W/Zr-based bulk
      metallic glass composites.
AB  - The interaction between active element Zr and W damages the W fibers and the
      interface and decreases the mechanical properties, especially the tensile
      strength of the W fibers reinforced Zr-based bulk metallic glass composites
      (BMGCs). From the viewpoint of atomic interaction, the W-Zr interaction can be
      restrained by adding minor elements that have stronger interaction with W into
      the alloy. The calculation about atomic interaction energy indicates that Ta and
      Nb preferred to segregate on the W substrate surface. Sessile drop experiment
      proves the prediction and corresponding in-situ coating appears at the interface.
      Besides, the atomic interaction mechanism was proven to be effective in many
      other systems by the sessile drop technique. Considering the interfacial
      morphology, Nb was added into the alloy to fabricate W/Zr-based BMGCs. As
      expected, the Nb addition effectively suppressed the W-Zr reaction and damage to
      W fibers. Both the compressive and tensile properties are improved obviously. 

PMID- 25758911
TI  - Factors to consider when selecting a nebulizer for a new inhaled drug product
      development program.
AB  - INTRODUCTION: Nebulizers are a common device choice for use when developing a new
      drug product, but the range of nebulizer devices available can make it difficult
      to select the right device. Increasingly, companies are only able to promote a
      drug with the device that was used during the development program; therefore,
      choosing the best device at an early stage is important in order to achieve
      commercial success. Selecting a device that is inappropriate for the intended
      drug can result in poor drug delivery from the nebulizer to the patient, which
      would have obvious implications for the development program. As device
      performance varies, it is important to ensure that the most appropriate device is
      chosen for the intended drug to ensure optimal drug delivery to the patient
      population. AREAS COVERED: In this review, the types of nebulizer devices
      available are highlighted, and the factors that should be taken into
      consideration when selecting the most appropriate device for a new drug are
      discussed. The review is broadly divided into drug, device, patient and trial
      characteristics. EXPERT OPINION: Efficient nebulizer devices that combine
      electronic monitoring capabilities as a form of telehealth are likely to provide
      superior drug delivery to patients and accurate clinical trial data. Their use in
      adaptive clinical trials may help to vastly reduce the time and costs associated
      with achieving drug approval.

PMID- 25758912
TI  - Characterization of the Shiga toxin-producing Escherichia coli O26 isolated from
      human in Poland between 1996 and 2014.
AB  - Shiga toxin-producing Escherichia coli (STEC) O26 infections can be comparable
      with STEC O157 infections in severity of the acute haemolytic-uremic syndrome HUS
      and long-term sequelae. Among O26 STEC isolates, highly virulent clone O26:H11/H-
      Sequence Type 29 (ST 29) emerged in Germany in mid-1990s and spread to European
      countries. However, up to date, no STEC O26:H11/H- belonging to ST29 has been
      documented in Poland. In this study, we determined the relationship and clonal
      structure, stx genotypes, plasmid gene profiles and antimicrobial resistance of
      nine human STEC O26:H11/H- strains from human patients in Poland between 1996 and
      2014. Of the 9 human STEC O26:H11/H- strains, two belonged to ST29 and were
      isolated from two children with HUS and renal failure with sepsis respectively.
      These strains showed the molecular characteristics of the emerging human
      pathogenic ST29 clone (stx1-, stx2a+, eae+, ehxA+, etpD+, katP-, espP-). The
      remaining STEC O26:H11/H- strains examined in this study, belonged to ST21, with
      plasmid genes profiles frequently reported in ST21 strains in Europe. STEC O26
      infections with serious human health consequences highlight the need of
      continuous surveillance of non-O157 STEC and implementation of the diagnostic
      approaches focused on their detection. Significance and impact of the study:
      These study provides the first data on the occurrence of emerging Shiga toxin
      producing Escherichia coli O26:H11 ST 29 clone in human patients in Poland. Those
      strains show the molecular characteristics of highly virulent new ST29 pathotype
      (stx1-, stx2a+, eae+ ehxA+, etpD+, katP-, espP-). These results demonstrated
      prompt efforts to implement diagnostic approaches detection of those pathogen in
      the European countries.

PMID- 25758913
TI  - Copper-catalyzed asymmetric allylation of chiral N-tert-butanesulfinyl imines:
      dual stereocontrol with nearly perfect diastereoselectivity.
AB  - Copper-catalyzed asymmetric allylation of chiral N-tert-butanesulfinyl imines has
      been described. Dual stereocontrol, through the combination of a chiral auxiliary
      and a chiral copper complex, has played an important role in achieving the nearly
      perfect diastereoselectivities (all dr > 99 : 1), especially for ketimine
      substrates. 

PMID- 25758914
TI  - Desensitization to febuxostat: report of two cases.

PMID- 25758915
TI  - Penicillin stability in prefilled syringes for the purpose of skin testing for
      drug allergy.

PMID- 25758916
TI  - Anaphylaxis management before and after implementation of guidelines in the
      pediatric emergency department.

PMID- 25758917
TI  - The HEDIS Medication Management for People with Asthma Measure is Not Related to
      Improved Asthma Outcomes.
AB  - BACKGROUND: A new Healthcare Effectiveness Data and Information Set (HEDIS)
      asthma quality-of-care measure designed to quantify patient adherence to asthma
      controller medication has been implemented. The relationship between this measure
      and asthma outcomes is unknown. OBJECTIVE: To examine the relationship between
      the HEDIS Medication Management for people with Asthma (MMA) measure and asthma
      outcomes. METHODS: Administrative data identified 30,040 patients who met HEDIS
      criteria for persistent asthma during 2012. These patients were classified as
      compliant or noncompliant with the MMA measure at the 75% and 50% threshold,
      respectively. The association between MMA compliance in 2012 and asthma outcomes
      in 2013 was determined. RESULTS: Patients who were 75% or 50% MMA compliant in
      2012 showed no clinically meaningful difference in asthma-related
      hospitalizations, emergency department visits, or rescue inhaler dispensing in
      2013 compared with those who were noncompliant. Stepwise comparison of patients
      who were 75% or more, 50% to 74%, and less than 50% MMA compliant showed no
      meaningful difference in asthma outcomes between groups. CONCLUSIONS: Compliance
      with the HEDIS MMA measure is not related to improvement in the asthma outcomes
      assessed (rescue inhaler dispensing, asthma-coded hospitalizations, or asthma
      coded emergency department visits).

PMID- 25758918
TI  - Trapping Poly(ADP-Ribose) Polymerase.
AB  - Recent findings indicate that a major mechanism by which poly(ADP-ribose)
      polymerase (PARP) inhibitors kill cancer cells is by trapping PARP1 and PARP2 to
      the sites of DNA damage. The PARP enzyme-inhibitor complex "locks" onto damaged
      DNA and prevents DNA repair, replication, and transcription, leading to cell
      death. Several clinical-stage PARP inhibitors, including veliparib, rucaparib,
      olaparib, niraparib, and talazoparib, have been evaluated for their PARP-trapping
      activity. Although they display similar capacity to inhibit PARP catalytic
      activity, their relative abilities to trap PARP differ by several orders of
      magnitude, with the ability to trap PARP closely correlating with each drug's
      ability to kill cancer cells. In this article, we review the available data on
      molecular interactions between these clinical-stage PARP inhibitors and PARP
      proteins, and discuss how their biologic differences might be explained by the
      trapping mechanism. We also discuss how to use the PARP-trapping mechanism to
      guide the development of PARP inhibitors as a new class of cancer therapy, both
      for single-agent and combination treatments. 

PMID- 25758921
TI  - Not all forms of collaborative care are the same.

PMID- 25758919
TI  - The ellagic acid derivative 4,4'-di-O-methylellagic acid efficiently inhibits
      colon cancer cell growth through a mechanism involving WNT16.
AB  - Ellagic acid (EA) and some derivatives have been reported to inhibit cancer cell
      proliferation, induce cell cycle arrest, and modulate some important cellular
      processes related to cancer. This study aimed to identify possible structure
      activity relationships of EA and some in vivo derivatives in their
      antiproliferative effect on both human colon cancer and normal cells, and to
      compare this activity with that of other polyphenols. Our results showed that
      4,4'-di-O-methylellagic acid (4,4'-DiOMEA) was the most effective compound in the
      inhibition of colon cancer cell proliferation. 4,4'-DiOMEA was 13-fold more
      effective than other compounds of the same family. In addition, 4,4'-DiOMEA was
      very active against colon cancer cells resistant to the chemotherapeutic agent 5
      fluoracil, whereas no effect was observed in nonmalignant colon cells. Moreover,
      no correlation between antiproliferative and antioxidant activities was found,
      further supporting that structure differences might result in dissimilar
      molecular targets involved in their differential effects. Finally, microarray
      analysis revealed that 4,4'-DiOMEA modulated Wnt signaling, which might be
      involved in the potential antitumor action of this compound. Our results suggest
      that structural-activity differences between EA and 4,4'-DiOMEA might constitute
      the basis for a new strategy in anticancer drug discovery based on these chemical
      modifications. 

PMID- 25758922
TI  - Esophagus cancer and occupational exposure to asbestos: results from a meta
      analysis of epidemiology studies.
AB  - The relationship between occupational asbestos exposure and esophagus cancer (EC)
      is not fully understood. We performed a meta-analysis to quantitatively assess
      the association. We systematically searched databases of PubMed, EMBASE, and Web
      of Science for studies with quantitative estimates of asbestos exposure and EC
      mortality. Pooled standardized mortality ratios (SMRs) and their corresponding
      95% confidence intervals (CIs) were calculated. Twenty cohort studies on EC and
      asbestos exposure were included in this meta-analysis. Overall, occupational
      exposure to asbestos was associated with an excess risk of EC (SMR = 1.24, 95%
      CI: 1.13-1.38, P < 0.001), with little evidence of heterogeneity among studies
      (I(2) = 0.0%, P = 0.682). Being male, exposure to chrysotile or mixed asbestos,
      working at textile industry, long study follow-up (>=20 years), Asia, Europe and
      America cohorts with larger cohort size (>500), and high-exposure group all
      contribute to significantly higher SMR. Publication bias was not detected
      (Egger's test P-value = 0.374). This meta-analysis suggested that occupational
      asbestos exposure might be associated with an increased risk of EC in male. High
      exposure level of asbestos could contribute to significantly higher risk of EC
      mortality. 

PMID- 25758923
TI  - Functional analysis of the Fusarium graminearum phosphatome.
AB  - Phosphatases are known to play important roles in the regulation of various
      cellular processes in eukaryotes. However, systematic characterization of the
      phosphatome has not been reported in phytopathogenic fungi. The wheat scab fungus
      Fusarium graminearum contains 82 putative phosphatases. The biological functions
      of each phosphatase were investigated in this study. Although 11 phosphatase
      genes appeared to be essential, deletion mutants of the other 71 phosphatase
      genes were obtained and characterized for changes in 15 phenotypes, including
      vegetative growth, nutrient response and virulence. Overall, the deletion of 63
      phosphatase genes resulted in changes in at least one of the phenotypes assayed.
      Interestingly, the deletion of four genes (Fg06297, Fg03333, Fg03826 and Fg07932)
      did not dramatically affect hyphal growth, but led to strongly reduced virulence.
      Western blot analyses showed that three phosphatases (Fg10516, Fg03333 and
      Fg12867) functioned as negative regulators of the mitogen-activated protein
      kinase signaling pathways. In addition, we found, for the first time, that
      FgCdc14 is dispensable for growth, but plays an important role in ribosome
      biogenesis. Overall, in this first functional characterization of the fungal
      phosphatome, phosphatases important for various aspects of hyphal growth,
      development, plant infection and secondary metabolism were identified in the
      phytopathogenic fungus F. graminearum. 

PMID- 25758924
TI  - Advanced material and approach for metal ions removal from aqueous solutions.
AB  - A Novel approach to remove metals from aqueous solutions has been developed. The
      method is based on a resin free, solid, non-toxic, microcrystalline
      bisphosphonate material, which has very low solubility in water (59 mg/l to ion
      free Milli-Q water and 13 mg/l to 3.5% NaCl solution). The material has been
      produced almost quantitatively on a 1 kg scale (it has been prepared also on a
      pilot scale, ca. 7 kg) and tested successfully for its ability to collect metal
      cations from different sources, such as ground water and mining process waters.
      Not only was this material highly efficient at collecting several metal ions out
      of solution it also proved to be regenerable and reusable over a number of
      adsorption/desorption, which is crucial for environmental friendliness. This
      material has several advantages compared to the currently used approaches, such
      as no need for any precipitation step. 

PMID- 25758925
TI  - Aging, women and health: from the pains of imprisonment to the pains of
      reintegration.
AB  - In this article, we examine the ways in which older women's experiences of
      imprisonment, aging, and health impact their lives. Specifically, we focus on the
      community reintegration experiences of older women who have served long prison
      sentences, exploring the lasting effects of imprisonment and aging on their
      physical and mental health. Two separate Canadian studies of reintegration,
      consisting of interviews with older reintegrating women, as well as the
      professionals who assist them in the community, are used to highlight older
      women's reintegrations. While researchers have argued that older women should
      face fewer challenges during reintegration and are more likely to succeed in the
      community than other reintegrating populations, we find that they experience many
      difficulties and barriers linked to their age, health and gender. 

PMID- 25758926
TI  - Effect of time in prison on prisoners' use of coping strategies.
AB  - Prisoners from two institutions (a low security and a high security prison) were
      studied to explore the coping strategies used in stressful situations, and the
      relationship between prison sentence length and the coping strategies employed.
      Prisoners completed the Eysenck Personality Questionnaire, and the Ways of Coping
      Scale. Coping strategies that focused on emotions, rather than on the source
      problem, were found to be most often employed. Shorter-term prisoners adopted
      problem-focused strategies more than longer-term prisoners, while longer-term
      prisoners adopted emotion-focused strategies more than shorter-term prisoners.
      These results are discussed with reference to the influence of the environment on
      coping strategy. 

PMID- 25758927
TI  - The prevalence of thyroid disorders among sexual and violent offenders and their
      co-occurrence with psychological symptoms.
AB  - The prevalence of thyroid abnormalities among 831 sexual, violent, and non
      violent non-sex offenders was found to be greater than found in the general
      population. Thyroid abnormalities were most common among violent offenders and
      among sex offenders who victimized children. Thyroid disorders were associated
      with psychotic diagnoses, delusions, mania, suicidal thoughts, and showed a trend
      to more suicide attempts. These disorders were undiagnosed in 49.1% of the cases
      prior to the present clinical assessment. Of these, 59.3% faced their first
      criminal charges, and the undiagnosed thyroid abnormalities may be important in
      the offenders' treatment and may be possible legal mitigating factors in some
      offenses. Results indicate that a routine endocrine evaluation with blood tests
      would be a valuable addition to the assessment of violent and sexual offenders. 

PMID- 25758928
TI  - Substitution treatment and HCV/HIV-infection in a sample of 31 German prisons for
      sentenced inmates.
AB  - Injection drug use (IDU) and IDU-related infectious diseases such as hepatitis C
      virus (HCV) and human immunodeficiency virus (HIV) infections are highly
      prevalent among prisoners worldwide. However, little is known about the
      prevalence of IDUs, HCV/HIV and the availability of respective treatment options
      in German prisons. Data provided by prison physicians of 31 prisons, representing
      14,537 inmates, were included in this analysis. The proportion of IDUs among all
      prisoners was 21.9%. Substitution treatment was available in three out of four
      prisons (74.2%). Overall, 1137 substitution treatments were provided annually
      with a wide range of treatment aims. The prevalence rate was 14.3% for HCV and
      1.2% for HIV. Around 5.5% of all HCV-infected prisoners were in antiviral
      treatment annually, 86.5% of all HIV-positive inmates in antiretroviral HIV
      treatment. Generally, substitution treatment, and HCV and HIV testing and
      treatment are available. However, due to abstinence-orientated treatment aims,
      substitution treatment is rarely available as maintenance treatment, and HCV/HIV
      treatment is mainly provided for patients with an existing treatment before
      imprisonment. The inconsistent data quality necessitates changes in prison
      related policy to improve surveillance and to generate aggregated data in German
      prisons. The selection process in this analysis might lead to overestimating the
      provision of substitution and antiviral HCV-treatment. 

PMID- 25758929
TI  - Women's health and prisons: it's time for urgent action. A report from the WHO
      Health in Prisons Project Annual Conference 'Prisons and Women's Health' 13
      November 2008, Kiev, Ukraine.
AB  - The strongest international recognition of the importance of women's health in
      prisons and the urgent need for radical change was highlighted of a WHO
      Conference held recently in Kiev, Ukraine. 

PMID- 25758930
TI  - UNODC and the National Administration of Penitentiaries launched harm reduction
      programme in Romanian prisons.
AB  - In February 2008, the National Administration of Penitentiaries and UNODC Project
      Office in Romania officially launched the common initiative of introducing harm
      reduction measures for people who inject drugs in three Romanian penitentiaries. 

PMID- 25758931
TI  - Autophagy does not lead to the asymmetrical hippocampal injury in chronic stress.
AB  - Chronic stress results in hippocampal injury, and impairs learning and memory
      ability of animals. However the cellular mechanisms underlying cell death within
      hippocampus remain elusive. The present employed the rat model of chronic
      unpredicted mild stress (CUMS) and examined the cellular mechanism responsible
      for learning and memory impairments. The results showed that in correlation to
      the decreased ability in novelty cognition and reverse learning, CUMS led to loss
      of CA3 neurons in hippocampus, especially in the right hippocampus.
      Interestingly, autophagy contributed to the cell loss but was asymmetrical on
      both sides. This suggested that CUMS resulted in asymmetrical hippocampal
      injuries, which is not fully determined by autophagy. 

PMID- 25758932
TI  - Influenza vaccination during pregnancy: a systematic review of fetal death,
      spontaneous abortion, and congenital malformation safety outcomes.
AB  - BACKGROUND: Pregnant women are considered the most important risk group for
      influenza vaccination. Despite this, the potential risk of harm from the vaccine
      on the fetus is a key factor in low uptake of the vaccine. This systematic review
      aimed to synthesize the best available evidence on the safety of influenza
      vaccination during pregnancy on fetal development. METHODS AND FINDINGS: A search
      of the literature was undertaken from the inception of each database up to March
      2014. Both observational and clinical trials were considered. Fetal outcomes were
      present in 19 observational studies, and 14 of those were primarily investigating
      the monovalent influenza A (H1N1) 2009 vaccine. There was significant
      methodological and clinical heterogeneity of the included studies and a narrative
      summary and tabling of results was performed. Fetal death outcomes for women in
      later pregnancy ranged from OR 0.34 to 2.95 with 95% confidence intervals
      crossing or below the null value. Spontaneous abortion less than 24 weeks ranged
      from HR 0.45 to OR 1.23, with 95% confidence intervals crossing or below the null
      value. Congenital malformations for women vaccinated during their first trimester
      ranged from OR 0.67 to 2.18 and imprecise confidence intervals crossed the null
      value. Included in this review were some high quality studies, although overall
      the studies have a high risk of selection and confounding bias. CONCLUSIONS:
      Results do not indicate that maternal influenza vaccination is associated with an
      increased risk of fetal death, spontaneous abortion, or congenital malformations.
      Statistical imprecision and clinical and methodological heterogeneity of the
      observational studies mean it is not possible to totally exclude adverse effects.
      Further studies investigating women vaccinated during their first trimester
      should be the highest priority to allow for more precise estimates, especially
      for spontaneous abortion, and congenital abnormality outcomes.

PMID- 25758933
TI  - Assessing the efficacy of an inactivated chicken anemia virus vaccine.
AB  - BACKGROUND: Chicken anemia virus (CAV) is an immunosuppressive virus that causes
      chicken infectious anemia (CIA) which is a highly contagious avian disease. CAV
      causes major economic losses in the poultry industry worldwide. The current CAV
      vaccine is a live attenuated strain administered in the drinking water that risks
      horizontal infection of other chickens. The purpose of this study was to develop
      a novel vaccine against CAV that can be administered safely using a highly
      pathogenic isolate inactivated with beta-propiolactone hydrolysis that would
      protect chicks from CAV. METHODS: Hens were vaccinated twice intramuscularly with
      a novel CAV GD-G-12 inactivated vaccine and the humoral immune responses of the
      hens and offspring were monitored by ELISA. A heterologous intramuscular
      challenge using the CAV strain GD-E-12 was conducted in the chicks hatched from
      vaccinated or unvaccinated hens. RESULTS: The vaccine strain, GD-G-12, was shown
      to be highly pathogenic prior to inactivation evidenced by thymic atrophy and
      bleeding, and weight loss. The inactivated vaccine was considered safe and showed
      no signs of pathogenicity. High titers of CAV specific antibodies were detected
      in the vaccinated hens and in their chicks, indicating vertical transfer of
      maternal antibodies. Furthermore, the chicks hatched from vaccinated hens were
      resistant to a heterologous CAV challenge and showed no signs of weight loss and
      thymic atrophy and bleeding. CONCLUSION: Our studies are proof of principle that
      inactivated GD-G-12 might be a novel vaccine candidate to prevent CAV infection,
      and highlight the utility of using an inactivated virus for this vaccine.

PMID- 25758934
TI  - microRNA regulation in cancer: One arm or two arms?

PMID- 25758936
TI  - Novel pnicogen bonding interactions with silylene as an electron donor:
      covalency, unusual substituent effects and new mechanisms.
AB  - An analogue of carbene, singlet silylene (H3P=N)2Si, was paired with the mono
      substituted phosphines XH2Y (X = P, As, and Sb; Y = F, Cl, Br, and I) to form
      unconventional pnicogen-bonded complexes. All structures have Cs symmetry except
      the Sb complex, showing a deviation from this symmetry due to the coexistence of
      H...H interactions. The P and As complexes have different geometries from
      conventional pnicogen-bonded ones because the Y-X...Si line shows a large
      deviation from the molecular plane composed of two N atoms and one Si atom of
      (H3P=N)2Si. This deviation can be attributed to a new formation mechanism of the
      pnicogen bond due to the combined result of the LPSi-> BD*X-Y and LPX-> LP*Si
      orbital interactions. Generally, the pnicogen bond becomes stronger in the order
      of F < Cl < Br < I and weaker in the order of P > As > Sb, exhibiting an
      unexpected substitution effect and dependence on the nature of the pnicogen atom.
      These orders are inconsistent with the MEP on the X atom but can be better
      explained by the above orbital interactions. The Si...X interaction displays a
      character of covalent or partially covalent interaction, evidenced by the high
      interaction energy of -59.9 to -105.4 kJ mol(-1) as well as the negative energy
      density and the great charge transfer.

PMID- 25758935
TI  - Loss of function mutation in glutamic pyruvate transaminase 2 (GPT2) causes
      developmental encephalopathy.
AB  - Intellectual disability is genetically heterogeneous, and it is likely that many
      of the responsible genes have not yet been identified. We describe three siblings
      with isolated, severe developmental encephalopathy. After extensive uninformative
      genetic and metabolic testing, whole exome sequencing identified a homozygous
      novel variant in glutamic pyruvate transaminase 2 (GPT2) or alanine transaminase
      2 (ALT2), c.459 C > G p.Ser153Arg that segregated with developmental
      encephalopathy in the family. This variant was predicted to be damaging by all in
      silico prediction algorithms. GPT2 is the gene encoding ALT2 which is responsible
      for the reversible transamination of alanine and 2-oxoglutarate to form pyruvate
      and glutamate. GPT2 is expressed in brain and is in the pathway to generate
      glutamate, an excitatory neurotransmitter. Functional assays of recombinant wild
      type and mutant ALT2 proteins demonstrated the p.Ser153Arg mutation resulted in a
      severe loss of enzymatic function. We suggest that recessively inherited loss of
      function GPT2 mutations are a novel cause of intellectual disability. 

PMID- 25758937
TI  - Differing properties of putative fast-spiking interneurons in the striatum of two
      rat strains.
AB  - Local circuits within the striatum of the basal ganglia include a small number of
      gamma-aminobutyric acid (GABA)-ergic fast-spiking interneurons (FSI). The number
      of these cells is reduced in disorders of behavioral control, but it is unknown
      whether this is accompanied by altered electrophysiological properties. The
      genetically hypertensive (GH) rat strain exhibits impulsiveness and
      hyperactivity. We investigated if resting-state FSI activity is affected in this
      strain using extracellular recordings. We also examined the effect of systemic
      amphetamine (AMPH), a stimulant drug used in the treatment of these particular
      behavioral deficits. Putative FSI (pFSI) were encountered less often in GH rats
      compared to the Wistar control strain. pFSI in GH rats also exhibited a higher
      mean firing rate, higher intraburst firing rate, lower interburst interval, and
      shorter bursts compared to controls. AMPH increased the mean overall firing rate
      of Wistar rat pFSI but did not significantly alter the firing properties of this
      subtype in GH rats. These differences in the resting-state electrophysiological
      activity of pFSI in GH rats point to them as a cell type of particular interest
      in understanding striatal functioning across different strains.

PMID- 25758938
TI  - Prognostic value of surgical margins during endoscopic resection of paranasal
      sinus malignancy.
AB  - BACKGROUND: Complete tumor resection with intraoperative frozen section control
      remains a central tenet of head and neck surgical oncology. The purpose of this
      study was to evaluate the significance of margins in predicting recurrence and
      disease status following endoscopic resection of sinonasal malignancy. METHODS:
      This single-institution observational cohort study was performed on 68 patients
      over a 5-year period who underwent curative minimally invasive endoscopic
      resection (MIER) for sinonasal malignancies. RESULTS: The mean age was 58.8 years
      and 69.1% were male. The mean follow-up after definitive MIER was 15.9 months. A
      mean of 10.8 margins were taken per surgery (range, 2 to 27). False-negative
      frozen section analysis was 22.1% for the entire cohort, but slightly higher at
      25.0% for T3 or T4 malignancies. At last follow-up, no evidence of disease (NED)
      status was noted in 60.0% of those with positive margins vs 83.0% in those with
      negative margins, respectively (p = 0.0795). Regional or distant recurrences were
      observed in 39.9% of patients with positive margins and 13.2% of those with
      negative margins, respectively (p = 0.0299). Disease-free survival (DFS) was 9.7
      months for patients with positive margins, whereas it was 15.9 months for
      patients with negative margins. CONCLUSION: Disease-free status as a function of
      residual microscopic disease did not prove to be statistically significant.
      However, positive margins were correlated with a statistically significant
      increase in regional or distant recurrence. This suggests that complete resection
      with clear margins can impact oncologic outcomes in patients managed by MIER for
      sinonasal cancers.

PMID- 25758939
TI  - Anxious attachment style predicts an enhanced cortisol response to group
      psychosocial stress.
AB  - Insecure attachment style is associated with poor health outcomes. A proposed
      pathway implicates the hypothalamic-pituitary-adrenal axis (HPA-axis),
      dysregulation of which is associated with a wide range of mental and physical ill
      health. However, data on stress reactivity in relation to attachment style is
      contradictory. This relationship was examined using the novel Trier Social Stress
      Test for groups (TSST-G): a group-based acute psychosocial stressor. Each
      participant, in the presence of other group members, individually performed
      public speaking and mental arithmetic tasks. Seventy-eight healthy young females
      (20.2 +/- 3.2 years), in groups of up to six participants completed demographic
      information and the Vulnerable Attachment Style Questionnaire (VASQ), and were
      then exposed to the TSST-G. Physiological stress reactivity was assessed using
      salivary cortisol concentrations, measured on seven occasions at 10-min
      intervals. Vulnerable attachment predicted greater cortisol reactivity
      independent of age, smoking status, menstrual phase and body mass index.
      Supplementary analysis indicated that insecure anxious attachment style (high
      scores on the insecurity and proximity-seeking sub-scales of the VASQ) showed
      greater cortisol reactivity than participants with secure attachment style.
      Avoidant attachment style (high scores for insecurity and low scores for
      proximity seeking) was not significantly different from the secure attachment
      style. Attachment style was not associated with the timing of the cortisol peak
      or post-stress recovery in cortisol concentrations. These findings in healthy
      young females indicate subtle underlying changes in HPA axis function in relation
      to attachment style and may be important for future mental health and well-being.

PMID- 25758940
TI  - Neuropathologically mixed Alzheimer's and Lewy body disease: burden of
      pathological protein aggregates differs between clinical phenotypes.
AB  - Multiple different pathological protein aggregates are frequently seen in human
      postmortem brains and hence mixed pathology is common. Mixed dementia on the
      other hand is less frequent and neuropathologically should only be diagnosed if
      criteria for more than one full blown disease are met. We quantitatively measured
      the amount of hyperphosphorylated microtubule associated tau (HP-tau), amyloid
      beta protein (Abeta) and alpha-synuclein (alpha-syn) in cases that were
      neuropathologically diagnosed as mixed Alzheimer's disease (AD) and neocortical
      Lewy body disease (LBD) but clinically presented either as dementia due to AD or
      LBD, the latter including dementia with Lewy bodies (DLB) and Parkinson's disease
      dementia (PDD). Our study group consisted of 28 cases (mean age, 76.11 SE: +/
      1.29 years; m:f, 17:11) of which 19 were neuropathologically diagnosed as mixed
      AD/DLB. Clinically, 8 mixed AD/DLB cases were diagnosed as AD (cAD), 8 as DLB
      (cDLB) and 3 as PDD (cPDD). In addition, we investigated cases that were both
      clinically and neuropathologically diagnosed as either AD (pure AD; n = 5) or
      DLB/neocortical LBD (pure DLB; n = 4). Sections from neocortical, limbic and
      subcortical areas were stained with antibodies against HP-tau, Abeta and alpha
      syn. The area covered by immunopositivity was measured using image analysis. cAD
      cases had higher HP-tau loads than both cDLB and cPDD and the distribution of HP
      tau in cAD was similar to the one observed in pure AD whilst cDLB showed
      comparatively less hippocampal HP-tau load. cPDD cases showed lower HP-tau and
      Abeta loads and higher alpha-syn loads. Here, we show that in neuropathologically
      mixed AD/DLB cases both the amount and the topographical distribution of
      pathological protein aggregates differed between distinct clinical phenotypes.
      Large-scale clinicopathological correlative studies using a quantitative
      methodology are warranted to further elucidate the neuropathological correlate of
      clinical symptoms in cases with mixed pathology.

PMID- 25758941
TI  - Stroke rehabilitation at home before and after discharge reduced disability and
      improved quality of life: a randomised controlled trial.
AB  - OBJECTIVE: To evaluate if home-based rehabilitation of inpatients improved
      outcome compared to standard care. DESIGN: Interventional, randomised,
      safety/efficacy open-label trial. SETTING: University hospital stroke unit in
      collaboration with three municipalities. SUBJECTS: Seventy-one eligible stroke
      patients (41 women) with focal neurological deficits hospitalised in a stroke
      unit for more than three days and in need of rehabilitation. INTERVENTIONS:
      Thirty-eight patients were randomised to home-based rehabilitation during
      hospitalization and for up to four weeks after discharge to replace part of usual
      treatment and rehabilitation services. Thirty-three control patients received
      treatment and rehabilitation following usual guidelines for the treatment of
      stroke patients. MAIN MEASURES: Ninety days post-stroke the modified Rankin Scale
      score was the primary endpoint. Other outcome measures were the modified Barthel
      100 Index, Motor Assessment Scale, CT-50 Cognitive Test, EuroQol-5D, Body Mass
      Index and treatment-associated economy. RESULTS: Thirty-one intervention and 30
      control patients completed the study. Patients in the intervention group achieved
      better modified Rankin Scale score (Intervention median = 2, IQR = 2-3; Control
      median = 3, IQR = 2-4; P=0.04). EuroQol-5D quality of life median scores were
      improved in intervention patients (Intervention median = 0.77, IQR = 0.66-0.79;
      Control median = 0.66, IQR = 0.56 - 0.72; P=0.03). The total amount of home-based
      training in minutes highly correlated with mRS, Barthel, Motor Assessment Scale
      and EuroQol-5DTM scores (P-values ranging from P<0.00001 to P=0.01). Economical
      estimations of intervention costs were lower than total costs of standard
      treatment. CONCLUSION: Early home-based rehabilitation reduced disability and
      increased quality of life. Compared to standard care, home-based stroke
      rehabilitation was more cost-effective.

PMID- 25758942
TI  - The effect of a structured programme to increase patient activity during
      inpatient stroke rehabilitation: a Phase I cohort study.
AB  - OBJECTIVE: To develop an intervention and undertake a proof-of-concept evaluation
      of its feasibility, acceptability, and impact on recorded patient activity levels
      during inpatient stroke rehabilitation. DESIGN: A longitudinal cohort design.
      SETTING: Three inpatient stroke rehabilitation services. SUBJECTS: Stroke
      survivors receiving inpatient rehabilitation. INTERVENTION: A programme designed
      to increase patient activity, including individualised patient timetables,
      independent practice, therapeutic group work, and structured social activities
      was developed and implemented without additional resource. MAIN MEASURES:
      Patients' recorded activity levels were compared for two weeks before and after
      implementation of the programme. Data regarding the estimated time spent in
      different types of activity were extracted from patient treatment records,
      patients' and therapists' diaries, or timetables (if used) to measure patient
      activity levels RESULTS: At baseline, recorded activity levels were low; patients
      undertook a mean of 61 minutes (SD = 39) of activity per day. After
      implementation of the programme, recorded activity levels significantly increased
      to a mean of 123 minutes (SD = 88) per day (p = 0.0001). The time spent in all
      types of recorded activity increased (p = 0.0001-0.002), except psychology where
      the increase did not reach significance (p = 0.670). CONCLUSIONS: A structured
      programme can significantly increase recorded patient activity levels during
      inpatient stroke rehabilitation without additional resource.

PMID- 25758943
TI  - A systematic review of the economic evidence for interventions for family carers
      of stroke patients.
AB  - OBJECTIVES: To examine the economic evidence for interventions aimed at family
      carers of stroke patients. DATA SOURCES: Searches (limited to those published in
      English since 1990) were performed in key databases along with hand searches of
      relevant papers. REVIEW METHODS: Papers were restricted to studies including any
      economic data (broadly defined) for any intervention targeting carers explicitly
      or explicitly referring to a carer element, beyond involving carers in the care
      or intervention for patients (i.e. more than just carers being invited to observe
      an intervention targeted at the patient). Two reviewers independently screened
      full papers and extracted data using guidance from the National Institute for
      Health and Care Excellence, and quality assessment using the Newcastle-Ottawa
      Quality Assessment Scale (cohort studies), the Delphi list (randomised controlled
      trials) and guidelines on economic quality from the British Medical Journal. Data
      were reviewed descriptively as meta analyses were inappropriate due to non
      comparability of studies. RESULTS: Ten papers were included in the review. These
      were heterogeneous in their design, intervention and economic analyses making
      comparison difficult. Only three of the ten papers included economic evaluations.
      All three reported that the intervention was less costly and had better or
      equivalent outcomes than the control comparator although two of these were based
      on the same intervention using the same dataset. CONCLUSION: There is some
      limited evidence that interventions for family carers of stroke patients are
      effective and cost effective. However, due to variation in the types of
      interventions examined, little can be concluded regarding implications for
      clinical practice.

PMID- 25758944
TI  - Eccentric exercise in adults with cardiorespiratory disease: a systematic review.
AB  - OBJECTIVE: To determine if eccentric exercise is effective, tolerable and safe
      for adults with chronic cardiorespiratory disease. DATA SOURCES: We searched
      electronic databases from inception until January 2015 (Medline, CINAHL, Embase,
      SportDiscus, PEDro, Cochrane Central and AMED) supplemented by citation tracking
      and reference list scanning. REVIEW METHODS: Included articles had to report
      effects of eccentric exercise, alone or as a primary component of intervention,
      of any intensity and duration, on adults with chronic cardiorespiratory disease.
      Trials needed to be reported as full text in a peer-reviewed journal and include
      control data (randomised, quasi-randomised and single group cross-over design
      trials). Any outcomes or comparison interventions were accepted. Methodological
      rigor was assessed using the PEDro scale. RESULTS: Of 22 potentially relevant
      articles, 10 met inclusion criteria. They reported results from seven trials with
      a total of 112 participants across the diseases. PEDro scores were low (median
      3). Eccentric exercise increased strength and mobility to comparable levels as
      concentric exercise, however, it did so with lower oxygen consumption (effect
      size as large as d = -3.07 (-4.12, -1.80)), and four-fold power output (effect
      size d = -3.60 (-5.03, -1.66)). There were no adverse events reported for
      eccentric exercise. Pain was avoided with familiarisation sessions and individual
      exercise prescription. CONCLUSION: Eccentric exercise is beneficial and at least
      comparable with traditional exercise in improving walking and strength for people
      with chronic cardiorespiratory disease. It was well tolerated and we identified
      no safety concerns for the use of this intervention for this population.

PMID- 25758945
TI  - Multiple-length-scale deformation analysis in a thermoplastic polyurethane.
AB  - Thermoplastic polyurethane elastomers enjoy an exceptionally wide range of
      applications due to their remarkable versatility. These block co-polymers are
      used here as an example of a structurally inhomogeneous composite containing nano
      scale gradients, whose internal strain differs depending on the length scale of
      consideration. Here we present a combined experimental and modelling approach to
      the hierarchical characterization of block co-polymer deformation. Synchrotron
      based small- and wide-angle X-ray scattering and radiography are used for strain
      evaluation across the scales. Transmission electron microscopy image-based finite
      element modelling and fast Fourier transform analysis are used to develop a multi
      phase numerical model that achieves agreement with the combined experimental data
      using a minimal number of adjustable structural parameters. The results highlight
      the importance of fuzzy interfaces, that is, regions of nanometre-scale structure
      and property gradients, in determining the mechanical properties of hierarchical
      composites across the scales. 

PMID- 25758946
TI  - Asymmetric transfer effects between cognitive and affective task disturbances.
AB  - Task-irrelevant features of a stimulus can disturb performance on a given task,
      and this can occur for cognitive reasons such as irrelevant stimulus position,
      and affective reasons such as high stimulus valence. The human brain adapts to
      such disturbances in order to ensure successful task performance. Adaptations can
      occur in a transient manner in response to recent events, and they can also be
      sustained to account for overall probabilities of disturbances. Here, we study
      the mutual interplay between affective and cognitive task disturbances under
      conditions of sustained conflict adaptation. More precisely, we examined the
      trajectory of finger movements in a speeded classification task and investigated
      whether adaptation to a high probability of spatial disturbances transfers to the
      impact of affective disturbances (Experiment 1) and whether adaptation to a high
      probability of affective disturbances transfers to the impact of spatial
      disturbances (Experiment 2). Our observations point towards an asymmetric
      transfer from adaptation to affective onto the processing of cognitive
      disturbances, but not the other way around. 

PMID- 25758947
TI  - A combination of histological analyses and uniaxial tensile tests to determine
      the material coefficients of the healthy and atherosclerotic human coronary
      arteries.
AB  - Atherosclerosis is considered as the most severe form of cardiovascular diseases
      as it alters the structure of the elastin and collagen and, consequently, the
      mechanical properties of the artery wall. The role of collagen fibers
      orientations in the mechanical properties of the healthy and atherosclerotic
      human coronary arteries so far has not been well determined. In this study, a
      fiber family based constitutive equation was employed to address the mechanical
      behavior of healthy and atherosclerotic human coronary arteries using the
      combination of histostructural and uniaxial data. A group of six healthy and
      atherosclerotic human coronary arteries was excised at autopsy and histological
      analyses were performed on each artery to determine the mean angle of collagen
      fibers. The preconditioned arterial tissues were then subjected to a series of
      quasi-static axial and circumferential loadings. The key role of fiber
      orientation was explicitly added into a proposed strain energy density function.
      The constrained nonlinear optimization method was used to determine the material
      coefficients based on the axial and circumferential extension data of the
      arteries. The material coefficients of coronary arteries were given with
      R(2)>=0.991. The results regardless of loading direction revealed a significant
      load-bearing capacity and stiffness of atherosclerotic arteries compared to the
      healthy ones (p<0.005). The optimized fiber angles were in good agreement with
      the experimental histological data as only 2.52% and 10.10% differences were
      observed for the healthy and atherosclerotic arteries, respectively. The stored
      energy function of the healthy arteries was found to be higher than that of
      atherosclerotic ones. These findings help us to understand the directional
      mechanical properties of coronary arteries which may have implications for
      different types of interventions and surgeries, including bypass, stenting, and
      balloon-angioplasty. 

PMID- 25758948
TI  - Acute inflammatory demyelinating polyneuropathy as a manifestation of chronic
      lymphoproliferative disorder of NK cells.

PMID- 25758949
TI  - Mycophenolate revisited.
AB  - The patent of mycophenolate mofetil (MMF) has expired, and for enteric-coated
      mycophenolate sodium (EC-MPS), this will happen in 2017. In the twenty years
      these drugs have been used, they have become extremely popular. In this review,
      the reasons for the popularity of mycophenolate are discussed, including the
      benefits compared to azathioprine. MMF and EC-MPS are therapeutically equivalent.
      Although neither is considered to be a narrow therapeutic index drug, this should
      not lead to careless switching between the innovator drug and generic
      formulations, or between one generic formulation and another. The pipeline of new
      immunosuppressive drugs is dry, and it is very likely that we will be using
      mycophenolate for many more years to come as a first-line immunosuppressive drug
      in our transplant population. Whether or not the development of donor-specific
      anti-HLA antibodies is related to drug exposure (mycophenolic acid
      concentrations) remains to be investigated. 

PMID- 25758950
TI  - Stereoselective nickel-catalyzed [2+2] cycloadditions of ene-allenes.
AB  - A stereoselective nickel-catalyzed [2+2] cycloaddition of ene-allenes is
      reported. This transformation encompasses a broad range of ene-allene substrates,
      thus providing efficient access to fused cyclobutanes from easily accessed pi
      components. A simple and inexpensive first-row catalytic system comprised of
      [Ni(cod)2 ] and dppf was used in this process, thus constituting an attractive
      approach to synthetically challenging cyclobutane frameworks under mild reaction
      conditions. 

PMID- 25758952
TI  - Socioeconomic status and ethnicity of deceased donor kidney recipients compared
      to their donors.
AB  - Public perception and misperceptions of socioeconomic disparities affect the
      willingness to donate organs. To improve our understanding of the flow of
      deceased donor kidneys, we analyzed socioeconomic status (SES) and racial/ethnic
      gradients between donors and recipients. In a retrospective cohort study,
      traditional demographic and socioeconomic factors, as well as an SES index, were
      compared in 56,697 deceased kidney donor and recipient pairs transplanted between
      2007 and 2012. Kidneys were more likely to be transplanted in recipients of the
      same racial/ethnic group as the donor (p < 0.001). Kidneys tended to go to
      recipients of lower SES index (50.5% of the time, p < 0.001), a relationship that
      remained after adjusting for other available markers of donor organ quality and
      SES (p < 0.001). Deceased donor kidneys do not appear to be transplanted from
      donors of lower SES to recipients of higher SES; this information may be useful
      in counseling potential donors and their families regarding the distribution of
      their organ gifts. 

PMID- 25758951
TI  - Hydrogen Sulfide Maintains Mitochondrial DNA Replication via Demethylation of
      TFAM.
AB  - AIMS: Hydrogen sulfide (H2S) exerts a wide range of actions in the body,
      especially in the modulation of mitochondrial functions. The normal replication
      of mitochondrial DNA (mtDNA) is critical for cellular energy metabolism and
      mitochondrial biogenesis. The aim of this study was to investigate whether H2S
      affects mtDNA replication and the underlying mechanisms. We hypothesize that H2S
      maintains mtDNA copy number via inhibition of Dnmt3a transcription and TFAM
      promoter methylation. RESULTS: Here, we demonstrated that deficiency of
      cystathionine gamma-lyase (CSE), a major H2S-producing enzyme, reduces mtDNA copy
      number and mitochondrial contents, and it inhibits the expressions of
      mitochondrial transcription factor A (TFAM) and mitochondrial marker genes in
      both smooth muscle cells and aorta tissues from mice. Supply of exogenous H2S
      stimulated mtDNA copy number and strengthened the expressions of TFAM and
      mitochondrial marker genes. TFAM knockdown diminished H2S-enhanced mtDNA copy
      number. In addition, CSE deficiency induced the expression of DNA
      methyltransferase 3a (Dnmt3a) and TFAM promoter DNA methylation, and H2S
      repressed Dnmt3a expression, resulting in TFAM promoter demethylation. We further
      found that H2S S-sulfhydrates transcription repressor interferon regulatory
      factor 1 (IRF-1) and enhances the binding of IRF-1 with Dnmt3a promoter after
      reduced Dnmt3a transcription. H2S had little effects on the expression of Dnmt1
      and Dnmt3b as well as on ten-eleven translocation methylcytosine dioxygenase 1,
      2, and 3. INNOVATION: A sufficient level of H2S is able to inhibit TFAM promoter
      methylation and maintain mtDNA copy number. CONCLUSION: CSE/H2S system
      contributes to mtDNA replication and cellular bioenergetics and provides a novel
      therapeutic avenue for cardiovascular diseases.

PMID- 25758954
TI  - Optimization of lactic ferment with quinoa flour as bio-preservative alternative
      for packed bread.
AB  - The consumers' demand for food with high nutritional quality and free of chemical
      additives increases the need to look for new products and preservation
      strategies. Quinoa (Chenopodium quinoa) is an Andean pseudocereal highly
      appreciated because of its nutritional properties. Moreover, it is an optimal
      substrate for growing and production of improved amounts of antifungal compounds
      by Lactobacillus plantarum CRL 778. The aim of this work was to optimize a lactic
      ferment for packaged breads with improved nutritional value and prolonged shelf
      life by applying a statistical experimental design model. The addition of 30 %
      quinoa to the wheat semiliquid ferment (QWF) could highly improve the amino acids
      release (4.3 g/L) during fermentation. Moreover, this quinoa proportion was
      sufficient to obtain the same concentration of the antifungal compounds,
      phenyllactic and hydroxiphenyllactic acids (PLA and OH-PLA) as with 100 % quinoa
      (ca. 36 and 51 mg/L, respectively). Statistical model analysis showed that
      citrate and skimmed milk enhanced significantly all evaluated parameters
      specially PLA (ca. 71 mg/L), HO-PLA (ca. 75 mg/L), and lactate (27 g/L) with a p
      value <0.005. The synergic effects of higher antifungal compounds production,
      acid release, and pH decrease allowed lowering the amount (about 50 %) of the
      chemical preservative calcium propionate commonly added to bread. Moreover, these
      breads show increased shelf life.

PMID- 25758953
TI  - Plastid establishment did not require a chlamydial partner.
AB  - Primary plastids descend from the cyanobacterial endosymbiont of an ancient
      eukaryotic host, but the initial selective drivers that stabilized the
      association between these two cells are still unclear. One hypothesis that has
      achieved recent prominence suggests that the first role of the cyanobiont was in
      energy provision for a host cell whose reserves were being depleted by an
      intracellular chlamydial pathogen. A pivotal claim is that it was chlamydial
      proteins themselves that converted otherwise unusable cyanobacterial metabolites
      into host energy stores. We test this hypothesis by investigating the origins of
      the key enzymes using sophisticated phylogenetics. Here we show a mosaic origin
      for the relevant pathway combining genes with host, cyanobacterial or bacterial
      ancestry, but we detect no strong case for Chlamydiae to host transfer under the
      best-fitting models. Our conclusion is that there is no compelling evidence from
      gene trees that Chlamydiae played any role in establishing the primary plastid
      endosymbiosis. 

PMID- 25758955
TI  - Recombinant Nogo-66 via soluble expression with SUMO fusion in Escherichia coli
      inhibits neurite outgrowth in vitro.
AB  - Nogo-66, a hydrophilic loop of 66 amino acids flank two hydrophobic domains of
      the Nogo-A C terminus, interacts with the Nogo-66 receptor (NgR) to exert
      numerous functions in the central nervous system (CNS). Nogo-66 has important
      roles in aspects of neuronal development, including cell migration, axon
      guidance, fasciculation, and dendritic branching, and in aspects of CNS
      plasticity, including oligodendrocyte differentiation and myelination. Here, the
      small ubiquitin-related modifier (SUMO) was fused to the target gene, Nogo-66,
      and the construct was expressed in Escherichia coli (E. coli). Under the optimal
      fermentation conditions, the soluble expression level of the fusion protein was
      33 % of the total supernatant protein. After cleaving the fusion proteins with
      SUMO protease and purifying them by Ni-NTA affinity chromatography, the yield and
      purity of recombinant Nogo-66 obtained by 10-L scale fermentation were 23 +/- 1.5
      mg/L and greater than 93 %, respectively. The authenticity of the recombinant
      Nogo-66 was confirmed by an electrospray ionization-mass spectrometry analysis.
      The functional analyses indicated that the recombinant Nogo-66 was capable of
      binding the NgR specifically. The immunofluorescence results showed that the
      recombinant Nogo-66 could significantly inhibit neurite outgrowth of rat
      pheochromocytoma (PC12) cells stimulated by nerve growth factor and cerebellar
      granule cells (CGCs). Furthermore, Nogo-66 inhibited neurite outgrowth by
      increasing the level of phosphorylated Rho-associated coiled-coil-containing
      protein kinase 2 (ROCK2), collapsin response mediator protein 2 (CRMP2), and
      myosin light chain (MLC). This study provided a feasible and convenient
      production method for generating sufficient recombinant Nogo-66 for experimental
      and clinical applications.

PMID- 25758956
TI  - In vitro and in vivo antibacterial activity of environmental bacteriophages
      against Pseudomonas aeruginosa strains from cystic fibrosis patients.
AB  - The goal of the study was to determine the relationship between in vitro/in vivo
      efficacy of environmental Pseudomonas phages and certain phenotypical properties
      of Pseudomonas aeruginosa (PA) strains. We studied the diversity between
      particular isolates and determined phage sensitivity in vitro and in vivo in the
      Galleria mellonella insect model. Twenty-eight lytic bacteriophages specific for
      PA were tested against 121 CF PA isolates including 29 mucoid PA strains. Most
      strains from cystic fibrosis (CF) patients were lysed by at least three phages
      (93.6 %), but completely insensitive strains were also present (6.4 %). Two
      phages PA5oct and KT28 exhibited high rates of lytic potency on 55-68 % of PA
      strains (72-86 % of mucoid isolates). We further explored phage activity against
      six PA strains (CF and non-CF) in vitro, comparing clonal differences in phage
      susceptibility with bacterial properties such as the ability to form biofilms,
      mucosity, twitching motility, and biochemical profiles. We observed the
      relationship between variation in phage susceptibility and Fourier transform
      infrared spectroscopy (FTIR) analysis in the spectra window of carbohydrates. The
      protective efficacy of two selected phages against PA PAO1 and 0038 infection was
      confirmed in vivo in G. mellonella larvae. Generally, the wax moth model results
      confirmed the data from in vitro assays, but in massive infection of CF isolates,
      the application of lytic phages probably led to the release of toxic compound
      causing an increase in larvae mortality. We assumed that apart of in vitro phage
      activity testing, a simple and convenient wax moth larvae model should be applied
      for the evaluation of in vivo effectiveness of particular phage preparations.

PMID- 25758957
TI  - Archaeal community diversity in municipal waste landfill sites.
AB  - Despite the pivotal role of archaea in methane production in landfills, the
      identity, ecology, and functional diversity of these microorganisms and their
      link to environmental factors remain largely unknown. We collected 11 landfill
      leachate samples from six geographically distinct landfills of different ages in
      China and analyzed the archaeal community by bar-coded 454 pyrosequencing. We
      retrieved 121,797 sequences from a total of 167,583 sequences (average length of
      464 bp). The archaeal community was geographically structured, and nonabundant
      taxa primarily contributed to the observed dissimilarities. Canonical correlation
      analysis (CCA) suggested that the total phosphorous (TP), nitrate, and
      conductivity are important drivers for shaping the archaeal community. The
      hydrogenotrophic methanogens Methanomicrobiales and Methanobacteriales greatly
      dominated 9 of 11 samples, ranging from 83.7 to 99.5 %. These methanogens also
      dominated the remaining two samples, accounting for 70.3 and 58.8 %,
      respectively. Interestingly, for all of the studied Chinese landfills, 16S rRNA
      analysis indicated the predominance of hydrogenotrophic methanogens.

PMID- 25758958
TI  - Optimization of recombinant expression enables discovery of novel cytochrome P450
      activity in rice diterpenoid biosynthesis.
AB  - The oxygenation reactions catalyzed by cytochromes P450 (CYPs) play critical
      roles in plant natural products biosynthesis. At the same time, CYPs are one of
      most challenging enzymes to functionally characterize due to the difficulty of
      recombinantly expressing these membrane-associated monooxygenases. In the course
      of investigating rice diterpenoid biosynthesis, we have developed a synthetic
      biology approach for functional expression of relevant CYPs in Escherichia coli.
      In certain cases, activity was observed for only one of two closely related
      paralogs although it seems clear that related reactions are required for
      production of the known diterpenoids. Here, we report that optimization of the
      recombinant expression system enabled characterization of not only these
      previously recalcitrant CYPs, but also discovery of additional activity relevant
      to rice diterpenoid biosynthesis. Of particular interest, CYP701A8 was found to
      catalyze 3beta-hydroxylation of syn-pimaradiene, which is presumably relevant to
      momilactone biosynthesis, while CYP71Z6 & 7 were found to catalyze multiple
      reactions, with CYP71Z6 catalyzing the production of 2alpha,3alpha-dihydroxy-ent
      isokaurene via 2alpha-hydroxy-ent-isokaurene, and CYP71Z7 catalyzing the
      production of 3alpha-hydroxy-ent-cassadien-2-one via 2alpha-hydroxy-ent
      cassadiene and ent-cassadien-2-one, which may be relevant to oryzadione and
      phytocassane biosynthesis, respectively. 

PMID- 25758959
TI  - Construction of a novel phenol synthetic pathway in Escherichia coli through 4
      hydroxybenzoate decarboxylation.
AB  - Phenol is a bulk chemical with lots of applications in the chemical industry.
      Fermentative production of phenol had been realized in both Pseudomonas putida
      and Escherichia coli by recruiting tyrosine phenol-lyase (TPL). The TPL pathway
      needs tyrosine as the direct precursor for phenol production. In this work, a
      novel phenol synthetic pathway was created in E. coli by recruiting 4
      hydroxybenzoate decarboxylase, which can convert 4-hydroxybenzoate to phenol and
      carbon dioxide. Activating 3-deoxy-D-arabino-heptulosonate-7-phosphate (DAHP)
      synthase and chorismate pyruvate lyase (UbiC) through plasmid overexpression led
      to 7- and 69-fold increase of phenol production, respectively, demonstrating that
      these two enzymes were the rate-limiting steps for phenol production. Genetically
      stable strains were then obtained by gene integration and gene modulation
      directly in chromosome. Phenol titer increased 147-fold (from 1.7 to 250 mg/L)
      after modulating the DAHP synthase, UbiC, and 4-hydroxybenzoate decarboxylase
      genes in chromosome. Five solvents were tested for two-phase extractive
      fermentation to eliminate phenol toxicity to E. coli cells. Tributyrin and
      dibutyl phthalate were the best two solvents for improving phenol production,
      leading to 23 and 30 % increase of total phenol production, respectively. Two
      phase fed-batch fermentation of the best strain Phe009 was performed in a 7 L
      fermentor, which produced 9.51 g/L phenol with a yield of 0.061 g/g glucose.

PMID- 25758960
TI  - Distribution, industrial applications, and enzymatic synthesis of D-amino acids.
AB  - D-Amino acids exist widely in microbes, plants, animals, and food and can be
      applied in pharmaceutical, food, and cosmetics. Because of their widespread
      applications in industry, D-amino acids have recently received more and more
      attention. Enzymes including D-hydantoinase, N-acyl-D-amino acid amidohydrolase,
      D-amino acid amidase, D-aminopeptidase, D-peptidase, L-amino acid oxidase, D
      amino acid aminotransferase, and D-amino acid dehydrogenase can be used for D
      amino acids synthesis by kinetic resolution or asymmetric amination. In this
      review, the distribution, industrial applications, and enzymatic synthesis
      methods are summarized. And, among all the current enzymatic methods, D-amino
      acid dehydrogenase method not only produces D-amino acid by a one-step reaction
      but also takes environment and atom economics into consideration; therefore, it
      is deserved to be paid more attention. 

PMID- 25758961
TI  - Effects of chromosomal gene copy number and locations on polyhydroxyalkanoate
      synthesis by Escherichia coli and Halomonas sp.
AB  - Chromosomal integration and expression of heterologous gene(s) are favored in
      industrial biotechnology due to the inheriting expression stability. Yet,
      chromosomal expression is commonly weaker than plasmid one. The effect on gene
      expression level at 13 chromosomal locations in Escherichia coli was investigated
      using the polyhydroxybutyrate (PHB) synthesis pathway encoded by a phaCAB operon
      as a reporter. When 11 copies of phaCAB were randomly integrated into 11 of the
      13 chromosomal locations, respectively, 5.2 wt% of PHB was produced. PHB (34.1
      wt%) was accumulated by a recombinant E. coli inserted chromosomally with 50
      copies of phaCAB in the active asnB site using a Cre-loxP recombination method.
      This PHB accumulation level was equivalent to a medium-copy-number plasmid
      expression system, suggesting the importance of chromosomal gene copy number for
      PHB production by E. coli. This result was used to manipulate a Halomonas strain.
      One copy of genes scpAB encoding methylmalonyl-CoA mutase and methylmalonyl-CoA
      decarboxylase was inserted into the strongest expression site porin in the
      chromosome of the 2-methylcitrate synthase (prpC) deleted mutant Halomonas TD08,
      leading to the synthesis of poly(hydroxybutyrate-co-hydroxyvalerate) (PHBV) from
      glucose as the sole carbon source. The chromosome-engineered strain produced PHBV
      consisting of 5-12 mol% 3-hydroxyvalerate (3HV) stably compared with unstable
      fluctuation of 7-25 mol% 3HV by a medium-copy-number plasmid system. These
      results demonstrated that chromosome engineering based on active transcriptional
      site and gene copy number is more feasible for polyhydroxyalkanoate (PHA)
      synthesis in Halomonas TD08 compared with in E. coli. 

PMID- 25758962
TI  - Fast discharge process of layered cobalt oxides due to high Na+ diffusion.
AB  - Sodium ion secondary battery (SIB) is a low-cost and ubiquitous secondary battery
      for next-generation large-scale energy storage. The diffusion process of large
      Na(+) (ionic radius is 1.12 A), however, is considered to be slower than that of
      small Li(+) (0.76 A). This would be a serious disadvantage of SIB as compared
      with the Lithium ion secondary battery (LIB). By means of the electrochemical
      impedance spectroscopy (EIS), we determined the diffusion constant (D) of Na(+)
      in thin films of O3- and P2-type NaCoO2 with layered structures. We found that
      the D values (~ 0.5-1.5 * 10(-10) cm(2)/s) of Na(+) are higher than those (< 1 *
      10(-11) cm(2)/s) of Li(+) in layered LiCoO2. Especially, the D values of O3
      NaCoO2 are even higher than those of P2-NaCoO2, probably because O3-NaCoO2 shows
      successive structural phase transitions from the O3, O'3, P'3, to P3 phases with
      Na(+) deintercalation. We further found that the activation energy (ED ~ 0.4 eV)
      for the Na(+) diffusion is significantly low in these layered cobalt oxides. We
      found a close relation between the relative capacity and the renormalized
      discharge rate ( = L(2)/DT, where L and T are the film thickness and discharge
      time, respectively). 

PMID- 25758963
TI  - Digital rectal examination can detect early prostate cancer.

PMID- 25758964
TI  - Up to 4000 mg of paracetamol a day is ineffective for acute low back pain.

PMID- 25758965
TI  - [Good advice from the family physician - not expensive but valuable].

PMID- 25758966
TI  - [CME. Urticaria].

PMID- 25758968
TI  - [Anxieties of patients before anesthesia - what information can the family
      physician provide?].
AB  - Patients' fears of anesthesia mostly focus on a possibly inadequate anesthetic
      effect, on postoperative wound pain and/or nausea and vomiting (PONV). Concerning
      the possibility of an inadequate anesthetic effect, patients usually express two
      different kinds of fears: first, that they might stay conscious during surgery
      ("Awareness") without it being noticed, and second that they might not wake up
      again after the operation or that they might sustain neurological damages or
      deficits after the anesthesia. Last but not least patients are afraid they might
      suffer from substantial pain after waking up from the anesthesia. In this article
      we take a closer look at these aspects and discuss ways and possibilities of
      handling them, suggesting useful approaches for the general practitioner when
      talking these issues through with his patients prior to an operation. 

PMID- 25758969
TI  - [When should palliative care for children with life-threatening illnesses
      begin?].
AB  - Paediatric Palliative Care in Switzerland is still in its infancy. In comparison
      to palliative care in adults, the knowledge about palliative care in children is
      limited. To facilitate the decision of when to start palliative care, an
      instrument for health professionals has been developed. The instrument, called
      Paediatric Palliative Screening Scale (PaPaS Scale), builds on five domains
      shedding light on the child's illness: 1) trajectory of disease and impact on
      daily activities; 2) treatment options and burden of treatment; 3) symptoms,
      controllability, and problem burden; 4) preferences of patient or parents; and 5)
      life expectancy. The aims of a reasonably starting palliative care are quality of
      life and the ability to actively create the rest of life. 

PMID- 25758970
TI  - [Use of interpreters in the context of insurance psychiatric expert assessment].
AB  - Limited knowledge of the German language represents a serious barrier for
      migrants into Switzerland to communicate successfully in a variety of health care
      settings, which may result not just in delayed access to treatment and poorer
      outcome, but also in difficulties judging eligibility for health and other social
      benefits. Especially when conducting disability and other occupational capacity
      evaluations, clinicians of all medical fields, but particularly psychiatrists,
      are required to obtain abundant information to allow them to perform a thorough
      mental health examination and to form a differentiated view of an evaluee's work
      capacity. Within a clinical context different translation and interpreting
      strategies are in use, and each strategy has its advantages and disadvantages.
      This mini-review describes the legal and modal aspects as well as the clinical
      practical implications of the use of such interpreting services during disability
      evaluations. 

PMID- 25758972
TI  - [Is the "polypill" in cardiovascular prevention an option].

PMID- 25758973
TI  - [According to the study antibiotics are not a risk factor for childhood bronchial
      asthma].

PMID- 25758974
TI  - [Ultrasound for dyspnea evaluation in an emergency enables faster diagnosis
      determination].

PMID- 25758978
TI  - Light stress and photoprotection in Chlamydomonas reinhardtii.
AB  - Plants and algae require light for photosynthesis, but absorption of too much
      light can lead to photo-oxidative damage to the photosynthetic apparatus and
      sustained decreases in the efficiency and rate of photosynthesis
      (photoinhibition). Light stress can adversely affect growth and viability,
      necessitating that photosynthetic organisms acclimate to different environmental
      conditions in order to alleviate the detrimental effects of excess light. The
      model unicellular green alga, Chlamydomonas reinhardtii, employs diverse
      strategies of regulation and photoprotection to avoid, minimize, and repair photo
      oxidative damage in stressful light conditions, allowing for acclimation to
      different and changing environments. 

PMID- 25758979
TI  - Colloid-probe AFM studies of the interaction forces of proteins adsorbed on
      colloidal crystals.
AB  - In recent years, colloid-probe AFM has been used to measure the direct
      interaction forces between colloidal particles of different size or surface
      functionality in aqueous media, as one can study different forces in symmerical
      systems (i.e., sphere-sphere geometry). The present study investigates the
      interaction between protein coatings on colloid probes and hydrophilic surfaces
      decorated with hexagonally close packed single particle layers that are either
      uncoated or coated with proteins. Controlled solvent evaporation from aqueous
      suspensions of colloidal particles (coated with or without lysozyme and albumin)
      produces single layers of close-packed colloidal crystals over large areas on a
      solid support. The measurements have been carried out in an aqueous medium at
      different salt concentrations and pH values. The results show changes in the
      interaction forces as the surface charge of the unmodified or modified particles,
      and ionic strength or pH of the solution is altered. At high ionic strength or
      pH, electrostatic interactions are screened, and a strong repulsive force at
      short separation below 5 nm dominates, suggesting structural changes in the
      absorbed protein layer on the particles. We also study the force of adhesion,
      which decreases with an increment in the salt concentration, and the interaction
      between two different proteins indicating a repulsive interaction on approach and
      adhesion on retraction. 

PMID- 25758980
TI  - Paraoxon and Pyridostigmine Interfere with Neural Stem Cell Differentiation.
AB  - Acetylcholinesterase (AChE) inhibition has been described as the main mechanism
      of organophosphate (OP)-evoked toxicity. OPs represent a human health threat,
      because chronic exposure to low doses can damage the developing brain, and acute
      exposure can produce long-lasting damage to adult brains, despite post-exposure
      medical countermeasures. Although the main mechanism of OP toxicity is AChE
      inhibition, several lines of evidence suggest that OPs also act by other
      mechanisms. We hypothesized that rat neural progenitor cells extracted on
      embryonic day 14.5 would be affected by constant inhibition of AChE from chronic
      exposure to OP or pyridostigmine (a reversible AChE blocker) during
      differentiation. In this work, the OP paraoxon decreased cell viability in
      concentrations >50 MUM, as measured with the MTT assay; however, this effect was
      not dose-dependent. Reduced viability could not be attributed to blockade of AChE
      activity, since treatment with 200 uM pyridostigmine did not affect cell
      viability, even after 6 days. Although changes in protein expression patterns
      were noted in both treatments, the distribution of differentiated phenotypes,
      such as the percentages of neurons and glial cells, was not altered, as
      determined by flow cytometry. Since paraoxon and pyridostigmine each decreased
      neurite outgrowth (but did not prevent differentiation), we infer that
      developmental patterns may have been affected.

PMID- 25758981
TI  - Enzymatic activities linked to cardiac energy metabolism of Trypanosoma evansi
      infected rats and their possible functional correlations to disease pathogenesis.
AB  - The aim of this study was to investigate the activities of important enzymes
      involved in the phosphoryl transfer network (adenylate kinase and creatine kinase
      (CK)), lactate dehydrogenase (LDH), respiratory chain complexes and biomarkers of
      cardiac function in rat experimentally infected by Trypanosoma evansi. Rat heart
      samples were evaluated at 5 and 15 days post-infection (PI). At 5 day PI, there
      was an increase in LDH and CK activities, and a decrease in respiratory chain
      complexes II, IV and succinate dehydrogenase activities. In addition, on day 15
      PI, a decrease in the respiratory chain complex IV activity was observed.
      Biomarkers of cardiac function were higher in infected animals on days 5 and 15
      PI. Considering the importance of the energy metabolism for heart function, it is
      possible that the changes in the enzymatic activities involved in the cardiac
      phosphotransfer network and the decrease in respiratory chain might be involved
      partially in the role of biomarkers of cardiac function of T. evansi-infected
      rats. 

PMID- 25758982
TI  - Does patellar denervation reduce post-operative anterior knee pain after total
      knee arthroplasty?
AB  - PURPOSE: The effectiveness of patellar denervation in reducing anterior knee pain
      and improving patient satisfaction and quality of life after total knee
      arthroplasty (TKA) is still controversial. A meta-analysis was conducted to try
      to settle the controversy. METHODS: The electronic databases PubMed, Web of
      Science, Embase, and Cochrane Library were systematically searched. Of 374 papers
      identified, seven randomised controlled trials involving 898 patients (983 knees)
      were eligible for data extraction and meta-analysis. RESULTS: Analysis showed
      that patellar denervation can significantly improve clinical outcomes for the
      first 12 months of follow-up after TKA, including anterior knee pain incidence (P
      = 0.008), visual analogue scale score (P < 0.001), patellar score (P < 0.001),
      Knee Society Score (P = 0.03), Knee Society Score function score (P = 0.03), and
      knee range of motion (P = 0.008). However, no statistical significance in
      outcomes was found between the patellar denervation group and no-denervation
      group for any of those parameters after 12 months of follow-up. CONCLUSION: The
      best currently available evidence suggests that patellar denervation can
      significantly reduce anterior knee pain incidence and improve early clinical
      outcomes after TKA. However, after a prolonged period of follow-up, this
      advantage seems to disappear. Even so, the use of patellar denervation in primary
      TKA is recommended because it is safe and produces good early clinical outcomes.
      LEVEL OF EVIDENCE: Therapeutic study, Level II.

PMID- 25758983
TI  - Comment on 'extension gap needs more than 1-mm laxity after implantation to avoid
      post-operative flexion contracture in total knee arthroplasty'.

PMID- 25758984
TI  - Novel technique for sternoclavicular joint reconstruction using a gracilis tendon
      autograft.
AB  - Surgical treatment of sternoclavicular joint instability can be challenging and
      carries the inherent risk of damaging vital structures if the posterior capsule
      is violated during surgery. In the current manuscript, a novel and easy technique
      for open reduction and tendon graft stabilization of the unstable
      sternoclavicular joint is presented. Analogous to other techniques, the graft is
      passed through drill holes in a figure-of-eight configuration. However, for this
      technique, the drill holes are placed in oblique direction from the anterior
      cortex towards the articular surface of the sternum, respectively the medial
      clavicle. By doing so, graft reconstruction is achieved without any need for
      retrosternal dissection and mobilization of the posterior capsule, thus
      minimizing the risk of severe intraoperative complications. LEVEL OF EVIDENCE: V.

PMID- 25758985
TI  - Multiplexed DNA detection using a gold nanorod-based fluorescence resonance
      energy transfer technique.
AB  - A fluorescence resonance energy transfer method for multiplex detection DNA based
      on gold nanorods had been successfully constructed. This method is simple, easy
      to operate, good selectivity, no requirement to label the probe molecule and can
      analyze simultaneously multiple targets of DNA in one sample. The limit of
      detection for the 18-mer, 27-mer and 30-mer targets is 0.72, 1.0 and 0.43 nM at a
      signal-to-noise ratio of 3. The recoveries of three targets were 96.57-98.07%,
      99.12-100.04% and 97.29-99.93%, respectively. The results show that the method
      can be used to analyze a clinical sample or a biological sample; it also can be
      used to develop new probes for rapid, sensitive and highly selective multiplex
      detection of analytes in real samples.

PMID- 25758986
TI  - Folate metabolism gene polymorphisms MTHFR C677T and A1298C and risk for
      preeclampsia: a meta-analysis.
AB  - OBJECTIVES: MTHFR C677T and A1298C have been associated with the risk of
      preeclampsia (PE), but with conflicting results. We performed this meta-analysis
      to derive a more precise estimation of the association between MTHFR
      polymorphisms and PE. STUDY DESIGN: An electronic search of PubMed and Chinese
      Biomedicine database was conducted to select studies for meta-analysis. 54 case
      controlled studies containing MTHFR C677T and A1298C gene polymorphisms were
      chosen, and odds ratio (OR) with confidence interval (CI) was used to assess the
      strength of this association. RESULT: These studies evaluated 7398 cases and
      11230 controls for MTHFR C677T. The overall results suggested that MTHFR C677T
      was associated with the risk of PE. (T vs. C: OR = 1.157, 95% CI: 1.057-1.266, p
      = 0.002; TT + CT vs. CC: OR = 1.165, 95% CI : 1.049-1.293, P = 0.004; TT vs. CT +
      CC: OR = 1.371, 95% CI: 1.153-1.63, p < 0.001). We also evaluated 1103 cases and
      988 controls for MTHFR A1298C but could not demonstrate an increased risk of PE
      for this polymorphism (p = 0.667). A symmetric funnel plot, the Egger's test (p =
      0.819) suggested a lack of publication bias. CONCLUSION: This meta-analysis
      supports the idea that MTHFR C677T genotype is associated with increased risk for
      PE, especially in the case of Asians and Caucasians.

PMID- 25758987
TI  - Age-associated alterations in the micromechanical properties of chromosomes in
      the mammalian egg.
AB  - PURPOSE: The incidence of aneuploidy in eggs from women of advanced reproductive
      age can exceed 60%, making the mammalian egg a unique model system to study the
      mechanisms of chromosome segregation errors. METHODS: Here we applied a novel
      biophysical chromosome stretching approach to quantify mechanical stiffness of
      meiotic chromosomes in the mammalian egg and then documented how these properties
      changed in a mouse model of physiologic reproductive aging. RESULTS: We found
      significant differences in chromosome micromechanics, and thus in higher order
      chromosome structure, coincident with advanced reproductive age, a time that is
      also unequivocally associated with an increase in egg aneuploidy. CONCLUSIONS:
      These findings have important implications for both reproductive and cancer
      biology where aneuploidy plays a central role in aging related disease states.

PMID- 25758988
TI  - Public perspectives on the use of preimplantation genetic diagnosis.
AB  - PURPOSE: To study the perspectives of the United States population towards the
      use of preimplantation genetic diagnosis (PGD) in various clinical scenarios.
      METHODS: Online cross-sectional population based questionnaire of a nationally
      representative sample according to age, gender, race/ethnicity, income, education
      and religion. RESULTS: A total of 1006 completed the questionnaire with an
      overall response rate of 94%. A majority supported PGD for diseases fatal early
      in life or those causing lifelong disability (72.9 and 66.7%, respectively); only
      48.0% supported PGD for diseases that manifest late in life. Respondents were
      more supportive of PGD for genetic diseases if they were aware of PGD prior to
      the survey (OR = 1.64; CI = 1.13-2.39). However, a small proportion were in favor
      of genetically-based trait selection: 21.1% supported PGD for sex selection,
      14.6% for physical traits and 18.9% for personality traits. Compared to women,
      men were nearly two- to three-fold more supportive of PGD for sex selection (OR =
      1.65; CI = 1.20-2.78), physical traits (OR = 2.38; CI = 1.60-3.48) and
      personality traits (OR = 2.31; CI =  .64-3.26). Compared to Caucasians, Asians
      (OR = 3.87; CI = 1.71-8.78) and African Americans (OR = 1.61; CI = 1.04-2.74)
      were more supportive of PGD for sex selection. CONCLUSIONS: In a nationally
      representative sample, a majority supported PGD to identify early onset diseases.
      We noted significant variation in opinions by sex, race, and education. There was
      more support among those with prior knowledge of PGD suggesting that education
      about PGD may foster favorable opinions. This study identifies public knowledge
      and attitudes that may be used to shape future research hypotheses and clinical
      policies.

PMID- 25758989
TI  - Laparoscopic excision of ovarian endometrioma does not exert a qualitative effect
      on ovarian function: insights from in vitro fertilization and single embryo
      transfer cycles.
AB  - PURPOSE: To evaluate whether laparoscopic excision of endometrioma exerts a
      qualitative effect on ovarian function. METHODS: A retrospective analysis of
      oocytes retrieved in 25 cycles of 21 patients undergoing IVF treatment with
      controlled ovarian stimulation. The number of oocytes recovered from ovaries with
      a history of excision of endometrioma (E-Ov) were compared to those from contra
      lateral healthy ovaries (H-Ov) as for the analysis of a quantitative effect of
      surgery. As for the analysis of a qualitative effect, 55 oocytes from E-Ov were
      compared to 128 oocytes from H-Ov in terms of normal fertilization rate and the
      rate of top-quality embryos per normally fertilized eggs. Furthermore, 10 embryos
      derived from oocytes recovered from E-Ov were compared to 24 embryos derived from
      oocytes from H-Ov in terms of clinical and on-going pregnancy rates per embryos
      in 34 single embryo transfer cycles. RESULTS: Mean number of oocytes recovered
      from E-Ov was significantly smaller than that from H-Ov (2.2 +/- 2.0 vs. 5.1 +/-
      3.3, P = 0.009). There was no difference between oocytes from E-Ov and H-Ov as
      for normal fertilization rate (63.6% vs. 69.5%, P = 0.43) and the rate of top
      quality embryos (40.0% vs. 49.0%, P = 0.34). Clinical and on-going pregnancy
      rates per embryos were also similar in embryos derived from oocytes recovered
      from E-Ov and H-Ov (40.0% vs. 25.0%, P = 0.39 and 20.0% vs. 20.8%, P = 0.96).
      CONCLUSIONS: The quality of oocytes recovered from the ovary with a history of
      laparoscopic excision of endometrioma is not inferior to the quality of oocytes
      from contra-lateral healthy ovary.

PMID- 25758990
TI  - Live birth rates using conventional in vitro fertilization compared to
      intracytoplasmic sperm injection in Bologna poor responders with a single oocyte
      retrieved.
AB  - PURPOSE: To compare reproductive outcomes following conventional in vitro
      fertilization (IVF) and intracytoplasmic sperm injection (ICSI) in poor
      responders fulfilling the Bologna criteria, with a single oocyte retrieved.
      METHODS: The present retrospective study included 243 Bologna poor responders
      with a single oocyte retrieved, who were categorized into three groups, depending
      on the fertilization method and semen quality (IVF non-male factor-IVF/NMF n =
      101; ICSI non-male factor ICSI/NMF n = 50; ICSI male factor-ICSI/MF n = 92).
      RESULTS: In IVF/NMF, ICSI/NMF and ICSI/MF similar fertilization rates [65.3, 66,
      58.7%, respectively], proportions of embryo formation [63.4, 60, 53.3%,
      respectively], proportions of good quality embryos [54.7, 56.7, 57.1%,
      respectively], implantation rates [8.9, 10, 8.2% respectively] and live birth
      rates per oocyte retrieval [5.0, 4.0, 3.3%, respectively] were observed.
      Degeneration rate of oocytes due to mechanical damage was significantly higher
      after ICSI in the ICSI/NMF and ICSI/MF groups (8 and 6.5%, respectively) compared
      to IVF/NMF (0%) (p = 0.02). CONCLUSIONS: Conventional IVF and ICSI are associated
      with similar reproductive outcomes in poor responder patients with a single
      oocyte retrieved. Therefore, the choice of fertilization method should be based
      primarily on semen quality, in combination with the patient's previous history. A
      randomized controlled trial should be performed to confirm this study's findings
      that conventional IVF and ICSI have similar reproductive outcomes in poor
      responders.

PMID- 25758991
TI  - A gene-based information gain method for detecting gene-gene interactions in case
      control studies.
AB  - Currently, most methods for detecting gene-gene interactions (GGIs) in genome
      wide association studies are divided into SNP-based methods and gene-based
      methods. Generally, the gene-based methods can be more powerful than SNP-based
      methods. Some gene-based entropy methods can only capture the linear relationship
      between genes. We therefore proposed a nonparametric gene-based information gain
      method (GBIGM) that can capture both linear relationship and nonlinear
      correlation between genes. Through simulation with different odds ratio, sample
      size and prevalence rate, GBIGM was shown to be valid and more powerful than
      classic KCCU method and SNP-based entropy method. In the analysis of data from 17
      genes on rheumatoid arthritis, GBIGM was more effective than the other two
      methods as it obtains fewer significant results, which was important for
      biological verification. Therefore, GBIGM is a suitable and powerful tool for
      detecting GGIs in case-control studies. 

PMID- 25758992
TI  - Redefining the MED13L syndrome.
AB  - Congenital cardiac and neurodevelopmental deficits have been recently linked to
      the mediator complex subunit 13-like protein MED13L, a subunit of the CDK8
      associated mediator complex that functions in transcriptional regulation through
      DNA-binding transcription factors and RNA polymerase II. Heterozygous MED13L
      variants cause transposition of the great arteries and intellectual disability
      (ID). Here, we report eight patients with predominantly novel MED13L variants who
      lack such complex congenital heart malformations. Rather, they depict a syndromic
      form of ID characterized by facial dysmorphism, ID, speech impairment, motor
      developmental delay with muscular hypotonia and behavioral difficulties. We
      thereby define a novel syndrome and significantly broaden the clinical spectrum
      associated with MED13L variants. A prominent feature of the MED13L neurocognitive
      presentation is profound language impairment, often in combination with
      articulatory deficits. 

PMID- 25758993
TI  - Two novel disease-causing variants in BMPR1B are associated with brachydactyly
      type A1.
AB  - Brachydactyly type A1 is an autosomal dominant disorder primarily characterized
      by hypoplasia/aplasia of the middle phalanges of digits 2-5. Human and mouse
      genetic perturbations in the BMP-SMAD signaling pathway have been associated with
      many brachymesophalangies, including BDA1, as causative mutations in IHH and GDF5
      have been previously identified. GDF5 interacts directly as the preferred ligand
      for the BMP type-1 receptor BMPR1B and is important for both chondrogenesis and
      digit formation. We report pathogenic variants in BMPR1B that are associated with
      complex BDA1. A c.975A>C (p.(Lys325Asn)) was identified in the first patient
      displaying absent middle phalanges and shortened distal phalanges of the toes in
      addition to the significant shortening of middle phalanges in digits 2, 3 and 5
      of the hands. The second patient displayed a combination of brachydactyly and
      arachnodactyly. The sequencing of BMPR1B in this individual revealed a novel
      c.447-1G>A at a canonical acceptor splice site of exon 8, which is predicted to
      create a novel acceptor site, thus leading to a translational reading frameshift.
      Both mutations are most likely to act in a dominant-negative manner, similar to
      the effects observed in BMPR1B mutations that cause BDA2. These findings
      demonstrate that BMPR1B is another gene involved with the pathogenesis of BDA1
      and illustrates the continuum of phenotypes between BDA1 and BDA2. 

PMID- 25758994
TI  - The type of variants at the COL3A1 gene associates with the phenotype and
      severity of vascular Ehlers-Danlos syndrome.
AB  - Vascular Ehlers-Danlos syndrome (vEDS) is a rare and severe autosomal dominant
      disorder caused by variants at the COL3A1 gene. Clinical characteristics and
      course of disease of 215 molecularly proven patients (146 index cases and 69
      relatives) were analysed. We found 126 distincts variants that were divided into
      five groups: (1) Glycine substitutions (n=71), (2) splice-site and in-frame
      insertions-deletions (n=36), (3) variants leading to haplo-insufficiency (n=7),
      (4) non-glycine missense variants within the triple helix (n=4 variants), and (5)
      non-glycine missense variants or in-frame insertions-deletions, in the N- or C
      terminal part of the protein (n=8). Overall, our cohort confirmed the severity of
      the disease with a median age at first complication of 29 years (IQR 22-39), the
      most frequent being arterial (48%) and digestive (24%) ruptures. Groups 2 and 1
      were significantly more severe than groups 3-5, with extreme median ages at first
      major complication of 23-47 years. Patients of groups 3-5 had a less typical
      phenotype and remarkably absence of digestive events. The distribution of glycine
      replacing amino acids was strongly biased towards more destabilizing residues of
      the collagen assembly. Thus the natural course of vEDS and the clinical phenotype
      of patients are influenced by the type of COL3A1 variant. This study also
      confirms that patients with variants located in the C- and N-termini or leading
      to haplo-insufficiency have milder course of the disease and less prevalent
      diagnostic criteria. These findings may help refine diagnostic strategy, genetic
      counselling and clinical care. 

PMID- 25758995
TI  - No evidence for increased mortality in SDHD variant carriers compared with the
      general population.
AB  - Germline variants in subunit D of the succinate dehydrogenase gene (SDHD
      variants) are associated with an increased risk of developing paragangliomas. The
      aim of this study was to compare mortality rates and survival in a Dutch cohort
      of SDHD variant carriers with those in the general population. The study was
      conducted at the Leiden University Medical Center, a tertiary referral center for
      patients with paragangliomas. Included subjects all tested positive for SDHD
      variants before 1 July 2012 and visited the departments of Otorhinolaryngology or
      Endocrinology at least once or had a diagnosed paraganglioma and a SDHD variant
      positive family history. Clinical data were retrieved from medical records,
      information on mortality was obtained from the Municipal Personal Records
      Database, and mortality rates for the Dutch population were obtained from the
      Dutch Central Bureau of Statistics, stratified by sex, age and date. SDHD variant
      carriers were followed from the date of first SDHD variant-related contact until
      death, emigration or 12 December 2012 and the standardized mortality ratio (SMR)
      was calculated. Two-hundred and seventy-five SDHD variant carriers were included
      in the study, of which 80% carried the c.274G>T, p.(Asp92Tyr) variant, had a mean
      duration of follow-up of 7.6 years, yielding 2242 person-years of observation for
      analysis. There were 18 deaths in the SDHD variant carrier group; two were
      paraganglioma related. The SMR for the whole cohort was 1.07 (95% confidence
      interval 0.67-1.73). In conclusion, mortality in SDHD variant carriers is not
      substantially increased. Additional studies are required to confirm these
      findings. 

PMID- 25758996
TI  - Genome-wide association analysis on five isolated populations identifies variants
      of the HLA-DOA gene associated with white wine liking.
AB  - Wine is the most popular alcoholic beverage around the world and because of its
      importance in society has been widely studied. Understanding what drives its
      flavor has been a quest for decades but much is still unknown and will be
      determined at least in part by individual taste preferences. Recently studies in
      the genetics of taste have uncovered the role of different genes in the
      determination of food preferences giving new insight on its physiology. In this
      context we have performed a genome-wide association study on red and white wine
      liking using three isolated populations collected in Italy, and replicated our
      results on two additional populations coming from the Netherland and Central Asia
      for a total of 3885 samples. We have found a significant association (P=2.1 * 10(
      8)) between white wine liking and rs9276975:C>T a polymorphism in the HLA-DOA
      gene encoding a non-canonical MHC II molecule, which regulates other MHC II
      molecules. The same association was also found with red wine liking (P=8.3 * 10(
      6)). Sex-separated analysis have also revealed that the effect of HLA-DOA is
      twice as large in women as compared to men suggesting an interaction between this
      polymorphism and gender. Our results are one of the first examples of genome-wide
      association between liking of a commonly consumed food and gene variants.
      Moreover, our results suggest a role of the MHC system in the determination of
      food preferences opening new insight in this field in general. 

PMID- 25758997
TI  - A prospective cohort study assessing clinical referral management & workforce
      allocation within a UK regional medical genetics service.
AB  - Ensuring patient access to genomic information in the face of increasing demand
      requires clinicians to develop innovative ways of working. This paper presents
      the first empirical prospective observational cohort study of UK multi
      disciplinary genetic service delivery. It describes and explores collaborative
      working practices including the utilisation and role of clinical geneticists and
      non-medical genetic counsellors. Six hundred and fifty new patients referred to a
      regional genetics service were tracked through 850 clinical contacts until
      discharge. Referral decisions regarding allocation of lead health professional
      assigned to the case were monitored, including the use of initial clinical
      contact guidelines. Significant differences were found in the cases led by
      genetic counsellors and those led by clinical geneticists. Around a sixth, 16.8%
      (109/650) of referrals were dealt with by a letter back to the referrer or re
      directed to another service provider and 14.8% (80/541) of the remaining patients
      chose not to schedule an appointment. Of the remaining 461 patients, genetic
      counsellors were allocated as lead health professional for 46.2% (213/461). A
      further 61 patients did not attend. Of those who did, 86.3% (345/400) were
      discharged after one or two appointments. Genetic counsellors contributed to 95%
      (784/825) of total patient contacts. They provided 93.7% (395/432) of initial
      contacts and 26.8% (106/395) of patients were discharged at that point. The
      information from this study informed a planned service re-design. More research
      is needed to assess the effectiveness and efficiency of different models of
      collaborative multi-disciplinary working within genetics services.

PMID- 25758999
TI  - Cortical GABAergic activity: a mediator of tic control?

PMID- 25758998
TI  - Genome-wide genetic investigation of serological measures of common infections.
AB  - Populations and individuals differ in susceptibility to infections because of a
      number of factors, including host genetic variation. We previously demonstrated
      that differences in antibody titer, which reflect infection history, are
      significantly heritable. Here we attempt to identify the genetic factors
      influencing variation in these serological phenotypes. Blood samples from >1300
      Mexican Americans were quantified for IgG antibody level against 12 common
      infections, selected on the basis of their reported role in cardiovascular
      disease risk: Chlamydia pneumoniae; Helicobacter pylori; Toxoplasma gondii;
      cytomegalovirus; herpes simplex I virus; herpes simplex II virus; human
      herpesvirus 6 (HHV6); human herpesvirus 8 (HHV8); varicella zoster virus;
      hepatitis A virus (HAV); influenza A virus; and influenza B virus. Pathogen
      specific quantitative antibody levels were analyzed, as were three measures of
      pathogen burden. Genome-wide linkage and joint linkage and association analyses
      were performed using ~1 million SNPs. Significant linkage (lod scores >3.0) was
      obtained for HHV6 (on chromosome 7), HHV8 (on chromosome 6), and HAV (on
      chromosome 13). SNP rs4812712 on chromosome 20 was significantly associated with
      C. pneumoniae (P=5.3 * 10(-8)). However, no genome-wide significant loci were
      obtained for the other investigated antibodies. We conclude that it is possible
      to localize host genetic factors influencing some of these antibody traits, but
      that further larger-scale investigations will be required to elucidate the
      genetic mechanisms contributing to variation in antibody levels. 

PMID- 25759000
TI  - Preliminary Characterization of Monofloral Coffea spp. Honey: Correlation between
      Potential Biomarkers and Pollen Content.
AB  - To determine the botanical origin of Coffea honey, a new method using proton
      nuclear magnetic resonance ((1)H NMR) is proposed. Integration of the aromatic
      region of the NMR spectrum of Coffea honey diluted in deuterated water allowed us
      to simultaneously quantify caffeine, theobromine, and trigonelline, as well as
      other compounds. The amounts of the three markers listed are significantly higher
      than those previously reported for Citrus spp. honey: caffeine ranged from 15 to
      98 mg/kg, theobromine from 25 to 160 mg/kg, and trigonelline from 23 to 86 mg/kg.
      The concurrent presence of these three substances is proposed as an indicator of
      the botanical origin of Coffea honey. Excellent correlation was found between
      these markers and the relative amounts of Coffea pollen measured in the same
      samples. 

PMID- 25759001
TI  - Do Health Reforms to Improve Quality Have Long-Term Effects? Results of a Follow
      Up on a Randomized Policy Experiment in the Philippines.
AB  - We tracked doctors who had previously participated in a randomized policy
      experiment in the Philippines. The original experiment involved 30 district
      hospitals divided equally into one control site and two intervention sites that
      increased insurance payments (full insurance support for children under 5 years
      old) or made bonus payments to hospital staff. During the 3 years of the
      intervention, quality-as measured by clinical performance and value vignettes
      improved and was sustained in both intervention sites compared with controls.
      Five years after the interventions were discontinued, we remeasured the quality
      of care of the doctors. We found that the intervention sites continued to have
      significantly higher quality compared with the control sites. The previously
      documented quality improvement in intervention sites appears to be sustained;
      moreover, it was subject to a very low (less than 1% per year) rate of decay in
      quality scores.

PMID- 25759003
TI  - Myasthenia gravis associated with ipilimumab and nivolumab in the treatment of
      small cell lung cancer.

PMID- 25759002
TI  - Is Self-Referral Associated with Higher Quality Care?
AB  - OBJECTIVE: To assess the extent to which patients self-refer to cancer
      specialists and whether self-referral is associated with better experiences and
      quality of care. DATA SOURCES: Data from surveys and medical record abstraction
      collected through the Cancer Care Outcomes Research and Surveillance Consortium.
      STUDY DESIGN: Observational study of patients with lung and colorectal cancer
      diagnosed from 2003 through 2005 in five geographically defined regions and five
      integrated health care delivery systems. METHODS: Multivariable logistic
      regression models used to assess factors associated with self-referral and
      propensity score-weighted doubly robust models to test the association between
      self-referral and experiences/quality of care. PRINCIPAL FINDINGS: Among 5,882
      patients, 9.7 percent of lung cancer patients and 14.9 percent of colorectal
      cancer patients self-referred to at least one cancer specialist. Black patients
      were less likely to self-refer than white patients (odds ratio: 0.48, 95 percent
      confidence interval: 0.35, 0.64); patients with high incomes (vs. low) and with a
      college degree (vs. non-high school graduates) were significantly more likely to
      self-refer. Self-referral was associated with lower ratings of overall physician
      communication for patients with lung cancer but, conversely, higher odds of
      curative surgery among patients with stage I/II lung cancer. CONCLUSIONS: A small
      but significant proportion of patients self-referred to their cancer specialists;
      rates varied by patient race and socioeconomic status. To the extent that self
      referral is associated with quality, it may reinforce disparities in care.

PMID- 25759004
TI  - In Search of a Safe Natural Sleep Aid.
AB  - Sleep deprivation is associated with an elevated risk of various diseases and
      leads to a poor quality of life and negative socioeconomic consequences. Sleep
      inducers such as drugs and herbal medicines may often lead to dependence and
      other side effects. L-Theanine (gamma-glutamylethylamide), an amino acid
      naturally found abundant in tea leaves, has anxiolytic effects via the induction
      of alpha brain waves without additive and other side effects associated with
      conventional sleep inducers. Anxiolysis is required for the initiation of high
      quality sleep. In this study, we review the mechanism(s), safety, and efficacy of
      L-theanine. Collectively, sleep studies based on an actigraph, the obstructive
      sleep apnea (OSA) sleep inventory questionnaire, wakeup after sleep onset (WASO)
      and automatic nervous system (ANS) assessment, sympathetic and parasympathetic
      nerve activities, and a pediatric sleep questionnaire (PSQ) suggest that the
      administration of 200 mg of L-theanine before bed may support improved sleep
      quality not by sedation but through anxiolysis. Because L-theanine does not
      induce daytime drowsiness, it may be useful at any time of the day. The no
      observable adverse effect level (NOAEL) for the oral administration of L-theanine
      was determined to be above 2000 mg/kg bw/day. KEY TEACHING POINTS: Sleep
      deprivation-associated morbidity is an increasing public health concern posing a
      substantial socioeconomic burden. Chronic sleep disorders may seriously affect
      quality of life and may be etiological factors in a number of chronic diseases
      such as depression, obesity, diabetes, and cardiovascular diseases. Most sleep
      inducers are sedatives and are often associated with addiction and other side
      effects. L-Theanine promotes relaxation without drowsiness. Unlike conventional
      sleep inducers, L-theanine is not a sedative but promotes good quality of sleep
      through anxiolysis. This review suggests that L-theanine is a safe natural sleep
      aid.

PMID- 25759005
TI  - Superhydrophobic surfaces for applications in seawater.
AB  - OBJECTIVE: Technological fields in which seawater is implied are numerorus,
      working in seawater (shipping, oil industry, marine aquaculture,..), and
      exploiting seawater in plants (cooling heat-exchange, desalination, power
      plants,..). All suffer from detrimental effects induced by biofouling mainly
      enhancing material failures and limiting energetic efficiencies. Among the
      remediation solutions, technologies coniugating economical, green and efficiency
      criteria should represent the direction. With the aim to meet these criteria,
      superhydrophobic (SH) technology attracted many researches for the protection of
      materials operating in contact with seawater. METHOD: In this work, the
      literature focusing on such technology for the protection of surfaces in contact
      with seawater has been reviewed, mainly focusing on boat and ship hull
      protection. RESULTS: Despite the growing interest around SH technology in
      seawater for fouling control and friction drag reduction of hulls, to date
      literature shows that superhydrophobicity in seawater is still limited if
      compared with a time window compatible with technological needs (set on years).
      An evaluation of the causes of early superhydrophobicity loss under operative
      conditions clearly indicates that, to the best of present knowledge, a SH surface
      cannot preserve this feature by itself alone (especially in real seawater).
      Hence, we have considered to highlight the behaviour of SH surfaces in seawater
      in relation to early stages of biocolonization (conditioning film and pioneering
      bioslime formation). Considering the annual costs sustained for the biofouling
      impact control, advantages coming from SH surfaces, in terms of foul control and
      friction drag reduction, would allow economical savings allowing to cover both
      the appliance of longevity keeping strategies of the SH surfaces and investments
      in green technologies of SH coating life cycle (production, storing). In addition
      a brief outlook is provided on technological fields exploiting seawater in
      pipelines (power and desalination plants), where the SH surface finishing finds
      potentially interesting application for fouling and corrosion prevention
      applications.

PMID- 25759006
TI  - Vegetarians have lower risk of colorectal cancers, study finds.

PMID- 25759007
TI  - The definition, purpose and value of pilot research.

PMID- 25759008
TI  - In vitro modulation of tumor necrosis factor alpha production in THP-1 cells by
      lactic acid bacteria isolated from healthy human infants.
AB  - The human microbiota is a source of probiotics capable of modulating the host
      immune system. In this study, we collected fecal samples from 100 healthy infants
      and isolated lactic acid bacteria which were screened for immune modulating
      effects on tumor necrosis factor alpha (TNF-alpha) production. Cell-free culture
      supernatants from 26 isolates were able to decrease TNF-alpha production in vitro
      and three of the isolates were selected as candidate probiotics (MSMC39-1, MSMC39
      3, MSMC57-1). These isolates were identified using 16S ribosomal DNA sequencing
      as Lactobacillus paracasei, Lactobacillus casei, and Weissella confusa
      respectively. All three isolates were acid tolerant and bile tolerant to pH 3.0
      and 4% bile respectively. Preparations of cell-free culture supernatants were
      processed and tested, and revealed that cell-free culture supernatants of
      isolates L. paracasei MSMC39-1, L. casei MSMC39-3, and W. confusa MSMC57-1
      decreased the production of TNF-alpha significantly and were heat resistant. Only
      L. paracasei MSMC39-1 supernatant was proteinase-K sensitive. The effects of
      viable bacteria, heat-killed bacteria, and sonicated bacteria were compared. The
      heat-killed preparations of isolate W. confusa MSMC57-1 decreased the production
      of TNF-alpha. Sonicated cell preparations did not significantly alter TNF-alpha
      production. For isolates L. paracasei MSMC39-1 and L. casei MSMC39-3, this
      suggests that a substance in the cell-free culture supernatant may be responsible
      for in vitro cytokine modulation. 

PMID- 25759009
TI  - P2-quinazolinones and bis-macrocycles as new templates for next-generation
      hepatitis C virus NS3/4a protease inhibitors: discovery of MK-2748 and MK-6325.
AB  - With the goal of identifying inhibitors of hepatitis C virus (HCV) NS3/4a
      protease that are potent against a wide range of genotypes and clinically
      relevant mutant viruses, several subseries of macrocycles were investigated based
      on observations made during the discovery of MK-5172. Quinazolinone-containing
      macrocycles were identified as promising leads, and optimization for superior
      cross-genotype and mutant enzyme potency as well as rat liver and plasma
      concentrations following oral dosing, led to the development of MK-2748.
      Additional investigation of a series of bis-macrocycles containing a fused 18-
      and 15-membered ring system were also optimized for the same properties, leading
      to the discovery of MK-6325. Both compounds display the broad genotype and mutant
      potency necessary for clinical development as next-generation HCV NS3/4a protease
      inhibitors.

PMID- 25759010
TI  - Treatment of secondary pulmonary hypertension with bosentan after left
      ventricular assist device implantation.
AB  - INTRODUCTION: Secondary pulmonary hypertension (PH) and right ventricular
      dysfunction are common and associated with poor prognosis in HF patients with
      left ventricular assist devices (LVADs). The role of pulmonary vasodilator
      therapy for these patients is currently unclear. AIMS: We sought to evaluate the
      safety and clinical course of patients treated with bosentan, an endothelin
      receptor antagonist, after the implementation of a LVAD. RESULTS: Between 10/2008
      and 5/2011, 50 consecutive patients with mean PAP >25 mmHg were treated with
      bosentan after LVAD implantation for a mean duration of 15.7 (+/-12.4) months.
      Ten patients discontinued the drug for possible side effects, including three for
      LFT abnormalities. Comparison of baseline to 6-month follow-up data revealed
      laboratory evidence for decongestion with a decrease in bilirubin (2.3-0.6, P <
      0.0001) and an improvement in pulmonary hemodynamics with echocardiographically
      calculated mean PVR decreasing 1.4 woods units (3.93 +/- 1.53 to 2.58 +/- 1.05, P
      < 0.0001). CONCLUSION: In this single-centered retrospective case series, we
      provide evidence that the tolerability of bosentan in LVAD-supported patients
      with secondary PH is comparable to prior experience in patients with heart
      failure.

PMID- 25759011
TI  - Promotion for the academic radiologist.

PMID- 25759012
TI  - OSBPL2 encodes a protein of inner and outer hair cell stereocilia and is mutated
      in autosomal dominant hearing loss (DFNA67).
AB  - BACKGROUND: Early-onset hearing loss is mostly of genetic origin. The complexity
      of the hearing process is reflected by its extensive genetic heterogeneity, with
      probably many causative genes remaining to be identified. Here, we aimed at
      identifying the genetic basis for autosomal dominant non-syndromic hearing loss
      (ADNSHL) in a large German family. METHODS: A panel of 66 known deafness genes
      was analyzed for mutations by next-generation sequencing (NGS) in the index
      patient. We then conducted genome-wide linkage analysis, and whole-exome
      sequencing was carried out with samples of two patients. Expression of Osbpl2 in
      the mouse cochlea was determined by immunohistochemistry. Because Osbpl2 has been
      proposed as a target of miR-96, we investigated homozygous Mir96 mutant mice for
      its upregulation. RESULTS: Onset of hearing loss in the investigated ADNSHL
      family is in childhood, initially affecting the high frequencies and progressing
      to profound deafness in adulthood. However, there is considerable intrafamilial
      variability. We mapped a novel ADNSHL locus, DFNA67, to chromosome 20q13.2
      q13.33, and subsequently identified a co-segregating heterozygous frameshift
      mutation, c.141_142delTG (p.Arg50Alafs*103), in OSBPL2, encoding a protein known
      to interact with the DFNA1 protein, DIAPH1. In mice, Osbpl2 was prominently
      expressed in stereocilia of cochlear outer and inner hair cells. We found no
      significant Osbpl2 upregulation at the mRNA level in homozygous Mir96 mutant
      mice. CONCLUSION: The function of OSBPL2 in the hearing process remains to be
      determined. Our study and the recent description of another frameshift mutation
      in a Chinese ADNSHL family identify OSBPL2 as a novel gene for progressive
      deafness.

PMID- 25759013
TI  - Controlled rod nanostructured assembly of diphenylalanine and their optical
      waveguide properties.
AB  - Diphenylalanine (FF) microrods were obtained by manipulating the fabrication
      conditions. Fourier transform infrared (FTIR), circular dichroism (CD),
      fluorescence (FL) spectroscopy, and X-ray diffraction (XRD) measurements revealed
      the molecular arrangement within the FF microrods, demonstrating similar
      secondary structure and molecular arrangement within FF microtubes and
      nanofibers. Accordingly, a possible mechanism was proposed, which may provide
      important guidance on the design and assembly manipulation of peptides and other
      biomolecules. Furthermore, characterization of a single FF microrod indicates
      that the FF microrod can act as an active optical waveguide material, allowing
      locally excited photoluminescence to propagate along the length of the microrod
      with coupling out at the microrod tips. 

PMID- 25759014
TI  - Vismodegib resistance in basal cell carcinoma: not a smooth fit.
AB  - In this issue of Cancer Cell, two complementary papers by Atwood and colleagues
      and Sharpe and colleagues show that basal cell carcinomas resistant to the
      Smoothened (SMO) inhibitor vismodegib frequently harbor SMO mutations that limit
      drug binding, with mutations at some sites also increasing basal SMO activity. 

PMID- 25759015
TI  - The GLU that holds cancer together: targeting GLUtamine transporters in breast
      cancer.
AB  - Many cancer cells require exogenous glutamine for proliferation, supply of TCA
      cycle intermediates, lipid synthesis, mTOR activity, and neutralization of
      reactive oxygen species. In this issue of Cancer Cell, Jeon and colleagues
      identify chemotherapy-induced endoplasmic reticulum stress as a novel strategy to
      target glutamine dependence. 

PMID- 25759016
TI  - Seek and destroy: relating cancer drivers to therapies.
AB  - In this issue of Cancer Cell, Rubio-Perez and colleagues present an in silico
      prescription strategy based on identifying somatic driver alterations and
      druggability options. Although relatively few patients were found treatable
      following current clinical guidelines, many more could benefit from drug
      repurposing, considering compounds at various stages of (pre-)clinical
      investigation.

PMID- 25759017
TI  - The pre-BCR to the rescue: therapeutic targeting of pre-B cell ALL.
AB  - Pre B-ALL is an aggressive cancer of the blood for which treatment of patients
      with relapsed and refractory disease remains a challenge. In this issue of Cancer
      Cell, Geng and colleagues surveyed the activation status of the pre-B cell
      receptor and comprehensively investigated downstream signaling mechanisms
      currently targetable with small molecule inhibitors. 

PMID- 25759018
TI  - IDH1/2 mutations and BCL-2 dependence: an unexpected Chink in AML's armour.
AB  - There is a pressing need to develop novel, mechanism-based therapeutic approaches
      that can be used to improve therapies for genetically defined tumor subtypes.
      Chan and colleagues have demonstrated recently that BCL-2 inhibitors can target
      IDH1/2 mutant cancers through a mutant-specific dependency in metabolic
      regulation. 

PMID- 25759019
TI  - Genomic analysis of smoothened inhibitor resistance in basal cell carcinoma.
AB  - Smoothened (SMO) inhibitors are under clinical investigation for the treatment of
      several cancers. Vismodegib is approved for the treatment of locally advanced and
      metastatic basal cell carcinoma (BCC). Most BCC patients experience significant
      clinical benefit on vismodegib, but some develop resistance. Genomic analysis of
      tumor biopsies revealed that vismodegib resistance is associated with Hedgehog
      (Hh) pathway reactivation, predominantly through mutation of the drug target SMO
      and to a lesser extent through concurrent copy number changes in SUFU and GLI2.
      SMO mutations either directly impaired drug binding or activated SMO to varying
      levels. Furthermore, we found evidence for intra-tumor heterogeneity, suggesting
      that a combination of therapies targeting components at multiple levels of the Hh
      pathway is required to overcome resistance.

PMID- 25759020
TI  - Smoothened variants explain the majority of drug resistance in basal cell
      carcinoma.
AB  - Advanced basal cell carcinomas (BCCs) frequently acquire resistance to Smoothened
      (SMO) inhibitors through unknown mechanisms. Here we identify SMO mutations in
      50% (22 of 44) of resistant BCCs and show that these mutations maintain Hedgehog
      signaling in the presence of SMO inhibitors. Alterations include four ligand
      binding pocket mutations defining sites of inhibitor binding and four variants
      conferring constitutive activity and inhibitor resistance, illuminating pivotal
      residues that ensure receptor autoinhibition. In the presence of a SMO inhibitor,
      tumor cells containing either class of SMO mutants effectively outcompete cells
      containing the wild-type SMO. Finally, we show that both classes of SMO variants
      respond to aPKC-iota/lambda or GLI2 inhibitors that operate downstream of SMO,
      setting the stage for the clinical use of GLI antagonists. 

PMID- 25759021
TI  - Regulation of glutamine carrier proteins by RNF5 determines breast cancer
      response to ER stress-inducing chemotherapies.
AB  - Many tumor cells are fueled by altered metabolism and increased glutamine (Gln)
      dependence. We identify regulation of the L-glutamine carrier proteins SLC1A5 and
      SLC38A2 (SLC1A5/38A2) by the ubiquitin ligase RNF5. Paclitaxel-induced ER stress
      to breast cancer (BCa) cells promotes RNF5 association, ubiquitination, and
      degradation of SLC1A5/38A2. This decreases Gln uptake, levels of TCA cycle
      components, mTOR signaling, and proliferation while increasing autophagy and cell
      death. Rnf5-deficient MMTV-PyMT mammary tumors were less differentiated and
      showed elevated SLC1A5 expression. Whereas RNF5 depletion in MDA-MB-231 cells
      promoted tumorigenesis and abolished paclitaxel responsiveness, SLC1A5/38A2
      knockdown elicited opposing effects. Inverse RNF5(hi)/SLC1A5/38A2(lo) expression
      was associated with positive prognosis in BCa. Thus, RNF5 control of Gln uptake
      underlies BCa response to chemotherapies. 

PMID- 25759022
TI  - A cytoplasmic NF-kappaB interacting long noncoding RNA blocks IkappaB
      phosphorylation and suppresses breast cancer metastasis.
AB  - NF-kappaB is a critical link between inflammation and cancer, but whether long
      non-coding RNAs (lncRNAs) regulate its activation remains unknown. Here, we
      identify an NF-KappaB Interacting LncRNA (NKILA), which is upregulated by NF
      kappaB, binds to NF-kappaB/IkappaB, and directly masks phosphorylation motifs of
      IkappaB, thereby inhibiting IKK-induced IkappaB phosphorylation and NF-kappaB
      activation. Unlike DNA that is dissociated from NF-kappaB by IkappaB, NKILA
      interacts with NF-kappaB/IkappaB to form a stable complex. Importantly, NKILA is
      essential to prevent over-activation of NF-kappaB pathway in inflammation
      stimulated breast epithelial cells. Furthermore, low NKILA expression is
      associated with breast cancer metastasis and poor patient prognosis. Therefore,
      lncRNAs can directly interact with functional domains of signaling proteins,
      serving as a class of NF-kappaB modulators to suppress cancer metastasis. 

PMID- 25759023
TI  - In silico prescription of anticancer drugs to cohorts of 28 tumor types reveals
      targeting opportunities.
AB  - Large efforts dedicated to detect somatic alterations across tumor genomes/exomes
      are expected to produce significant improvements in precision cancer medicine.
      However, high inter-tumor heterogeneity is a major obstacle to developing and
      applying therapeutic targeted agents to treat most cancer patients. Here, we
      offer a comprehensive assessment of the scope of targeted therapeutic agents in a
      large pan-cancer cohort. We developed an in silico prescription strategy based on
      identification of the driver alterations in each tumor and their druggability
      options. Although relatively few tumors are tractable by approved agents
      following clinical guidelines (5.9%), up to 40.2% could benefit from different
      repurposing options, and up to 73.3% considering treatments currently under
      clinical investigation. We also identified 80 therapeutically targetable cancer
      genes.

PMID- 25759024
TI  - A functional landscape of resistance to ALK inhibition in lung cancer.
AB  - We conducted a large-scale functional genetic study to characterize mechanisms of
      resistance to ALK inhibition in ALK-dependent lung cancer cells. We identify
      members of known resistance pathways and additional putative resistance drivers.
      Among the latter were members of the P2Y purinergic receptor family of G-protein
      coupled receptors (P2Y1, P2Y2, and P2Y6). P2Y receptors mediated resistance in
      part through a protein-kinase-C (PKC)-dependent mechanism. Moreover, PKC
      activation alone was sufficient to confer resistance to ALK inhibitors, whereas
      combined ALK and PKC inhibition restored sensitivity. We observed enrichment of
      gene signatures associated with several resistance drivers (including P2Y
      receptors) in crizotinib-resistant ALK-rearranged lung tumors compared to
      treatment-naive controls, supporting a role for these identified mechanisms in
      clinical ALK inhibitor resistance. 

PMID- 25759026
TI  - Vitamin D supplementation protects against bone loss following inhalant organic
      dust and lipopolysaccharide exposures in mice.
AB  - Systemic bone loss is associated with airway inflammatory diseases; yet,
      strategies to halt disease progression from inhalant exposures are not clear.
      Vitamin D might be a potentially protective approach against noxious respirable
      environmental exposures. We sought to determine whether vitamin D supplementation
      represents a viable lung- and bone-protective strategy following repetitive
      inhalant treatments with organic dust extract (ODE) or lipopolysaccharide (LPS)
      in mice. C57BL/5 mice were maintained on diets with low (1 IU/D/g) or high (10
      IU/D/g) vitamin D for 5 weeks and treated with ODE from swine confinement
      facilities, LPS, or saline daily for 3 weeks per established intranasal
      inhalation protocol. Lungs, hind limbs, and sera were harvested for experimental
      outcomes. Serum 25-hydroxyvitamin D levels were tenfold different between low and
      high vitamin D treatment groups with no differences between inhalant agents and
      saline treatments. Serum calcium levels were not affected. There was no
      difference in the magnitude of ODE- or LPS-induced inflammatory cell influx or
      lung histopathology between high and low vitamin D treatment groups. However,
      high vitamin D treatment reversed the loss of bone mineral density, bone volume,
      and bone micro-architecture deterioration induced by ODE or LPS as determined by
      micro-CT analysis. Bone-resorbing osteoclasts were also reduced by high vitamin D
      treatment. In the low vitamin D treatment groups, ODE induced the greatest degree
      of airway inflammatory consequences, and LPS induced the greatest degree of bone
      loss. Collectively, high-concentration vitamin D was protective against systemic
      bone loss, but not airway inflammation, resulting from ODE- or LPS-induced airway
      injury.

PMID- 25759025
TI  - Self-enforcing feedback activation between BCL6 and pre-B cell receptor signaling
      defines a distinct subtype of acute lymphoblastic leukemia.
AB  - Studying 830 pre-B ALL cases from four clinical trials, we found that human ALL
      can be divided into two fundamentally distinct subtypes based on pre-BCR
      function. While absent in the majority of ALL cases, tonic pre-BCR signaling was
      found in 112 cases (13.5%). In these cases, tonic pre-BCR signaling induced
      activation of BCL6, which in turn increased pre-BCR signaling output at the
      transcriptional level. Interestingly, inhibition of pre-BCR-related tyrosine
      kinases reduced constitutive BCL6 expression and selectively killed patient
      derived pre-BCR(+) ALL cells. These findings identify a genetically and
      phenotypically distinct subset of human ALL that critically depends on tonic pre
      BCR signaling. In vivo treatment studies suggested that pre-BCR tyrosine kinase
      inhibitors are useful for the treatment of patients with pre-BCR(+) ALL.

PMID- 25759027
TI  - PTEN-Foxo1 signaling triggers HMGB1-mediated innate immune responses in acute
      lung injury.
AB  - PTEN is a multifunctional phosphatase that regulates immune responses through a
      PI3K/Akt signaling cascade. HMGB1 plays an important role in the initiation of
      innate immune responses to induce acute lung injury (ALI). This study was
      designed to investigate the role of PTEN/Foxo1 signaling in the regulation of in
      vivo and in vitro innate immune responses in ALI. Using a mouse model of ALI,
      wild-type (WT) and myeloid-specific PTEN knockout (PTEN(M-KO)) mice were
      instilled with a recombinant HMGB1 (rHMGB1) or PBS. In some experiments, Foxo1
      siRNA or non-specific siRNA was injected into mice 6 h prior to rHMGB1
      instillation into lung. We found that rHMGB1 treatment in WT mice increased the
      expression of PTEN, Foxo1, TLR4, and NF-kappaB in alveolar macrophages from WT
      mice. However, macrophage-specific PTEN ablation resulted in reduced Foxo1 and
      TLR4 while increasing beta-catenin (Ser552) and Akt (Ser473) phosphorylation in
      these cells. Knockdown of Foxo1 with siRNA administration in WT mice ameliorated
      lung injury and inhibited myeloperoxidase activity followed by rHMGB1 treatment,
      which was accompanied by decreased mRNA expression coding for TNF-alpha, IL
      1beta, MIP2, and IP-10. Moreover, Foxo1 knockdown inhibited the expression of
      TLR4-dependent IRF3 and IFN-beta both in vitro and in vivo. These results
      demonstrate that PTEN/Foxo1 signaling is critical for triggering HMGB1-mediated
      innate TLR4 activation during ALI. By identifying the molecular signaling
      pathways within innate immune system, our studies provide the potential
      therapeutic targets for ALI.

PMID- 25759028
TI  - Angiotensin II and Cardiovascular-Renal Remodelling in Hypertension: Insights
      from a Human Model Opposite to Hypertension.
AB  - Insights into the Angiotensin II (Ang II) signalling pathways have been provided
      by extensive studies using Bartter's/Gitelman's syndromes patients. These
      syndromes are characterized by activation of the renin-angiotensin-aldosterone
      system but do not develop hypertension and cardiovascular remodelling, therefore
      represent a mirror image of hypertension and clinically manifest themselves as
      the opposite of hypertension. The short and the long-term signalling of Ang II
      remain an important matter of investigation to shed light on mechanisms
      responsible for the pathophysiology of hypertension and its long-term
      complications, such as cardiovascular remodelling and atherogenesis. In
      particular the long-term signalling of Ang II is involved in the pathophysiology
      of cardiovascular-renal remodelling, inflammatory and hypertrophic responses in
      which the relationship between RhoA/Rho kinase pathway and NO system plays a
      crucial role. This review reports the results of our studies in Bartter's and
      Gitelman's syndromes to get better insight these processes and the role of Ang II
      signaling. The information obtained from the studies in Bartter's/Gitelman's
      patients can, in fact, clarify, confirm or be used to gather more general data on
      the biochemical mechanisms responsible for the pathophysiology of hypertension
      and its long-term complications and could contribute to identify additional
      potential significant targets of therapy.

PMID- 25759030
TI  - An efficient synthesis of [1,3]dioxolo[4,5-g]thieno[3,4-b]quinolin-8(5H)-ones as
      novel thiazapodophyllotoxin analogues with potential anticancer activity.
AB  - A catalyst-free synthesis of 6,9-dihydro-[1,3]dioxolo[4,5-g]thieno[3,4-b]quinolin
      8(5H)-ones as novel analogues of podophyllotoxins was developed by a three
      component reaction of aldehydes, ethyl 2,4-dioxotetrahydrothiophene-3-carboxylate
      and 3,4-(methylenedioxy)aniline. This methodology not only provides new chemical
      library for the screening of anticancer activity, but also features excellent
      isolated yields, short reaction time, simple work up procedure and little
      environmental impact.

PMID- 25759029
TI  - Cytokine response in mouse bone marrow derived macrophages after infection with
      pathogenic and non-pathogenic Rift Valley fever virus.
AB  - Rift Valley fever virus (RVFV) is the most pathogenic member of the genus
      Phlebovirus within the family Bunyaviridae, and can cause severe disease in
      humans and livestock. Until recently, limited information has been published on
      the cellular host response elicited by RVFV, particularly in macrophages and
      dendritic cells, which play critical roles in stimulating adaptive and innate
      immune responses to viral infection. In an effort to define the initial response
      of host immunomodulatory cells to infection, primary mouse bone marrow derived
      macrophages (BMDM) were infected with the pathogenic RVFV strain ZH501, or
      attenuated strains MP-12 or MP-12 based Clone13 type (rMP12-C13 type), and
      cytokine secretion profiles examined. The secretion of T helper (Th)1-associated
      antiviral cytokines, chemokines and various interleukins increased rapidly after
      infection with the attenuated rMP12-C13 type RVFV, which lacks a functional NSs
      virulence gene. In comparison, infection with live-attenuated MP-12 encoding a
      functional NSs gene appeared to cause a delayed immune response, while pathogenic
      ZH501 ablates the immune response almost entirely. These data demonstrate that
      NSs can inhibit components of the BMDM antiviral response and supports previous
      work indicating that NSs can specifically regulate the type I interferon response
      in macrophages. Furthermore, our data demonstrate that genetic differences
      between ZH501 and MP-12 reduce the ability of MP-12 to inhibit antiviral
      signalling and subsequently reduce virulence in BMDM, demonstrating that viral
      components other than NSs play a critical role in regulating the host response to
      RVFV infection. 

PMID- 25759031
TI  - Design, synthesis and docking study of novel tetracyclic oxindole derivatives as
      alpha-glucosidase inhibitors.
AB  - A series of novel tetracyclic oxindole derivatives were synthesized via tandem
      Suzuki coupling-Michael addition reaction catalyzed by palladium. Twenty
      derivatives were designed and synthesized in 6-8 steps in 8-20% overall yields.
      Their structures were confirmed by (1)H, (13)C NMR and LC/MS. These compounds
      were evaluated for alpha-glucosidase inhibitory activity in vitro. Compounds 7c,
      7d, 7e, 7g, 7h, and 7i exhibited IC50 values of 32.3, 12.1, 15.7, 29.0, 16.0, and
      4.8 MUM, respectively, with potency all higher than that of the control standard
      acarbose (IC50=115.8 MUM). Molecular docking studies revealed the existence of
      potential hydrogen bonding and hydrophobic interaction between the enzyme and the
      active compound 7i.

PMID- 25759032
TI  - Synthesis and binding properties of new long-chain 4-substituted piperazine
      derivatives as 5-HT1A and 5-HT7 receptor ligands.
AB  - New long-chain 4-substituted piperazines linked to a thienopyrimidine or a
      quinazoline system were synthesized and tested for their binding properties on
      human cloned 5-HT1A and 5-HT7 serotonin receptors. Some structural modifications,
      concerning tree main portions, that is, terminal fragment, chain length, and aryl
      substituents, were examined. The 2- and 3-substituted thienopyrimidinone and
      quinazolinone systems were selected as terminal fragment and a chain length of
      four or five methylene units was set. Explored aryl substituents were phenyl,
      phenylmethyl, 3- or 4-chlorophenyl, and 2-ethoxyphenyl. Title compounds showed
      affinity for 5-HT1A and 5-HT7 receptors. In particular, 2-ethoxyphenyl
      derivatives 40 and 45 displayed Ki values in the nanomolar range on both
      receptors, acting as dual ligands. 

PMID- 25759033
TI  - Universities and sponsored research: indirect cost recovery and the law of
      diminishing return.

PMID- 25759036
TI  - [Learning outcomes of six-year pharmaceutical education program].

PMID- 25759035
TI  - Pharmacokinetics of anti-TB drugs in Malawian children: reconsidering the role of
      ethambutol.
AB  - BACKGROUND: Current guidelines for dosing of anti-TB drugs in children advocate
      higher doses for rifampicin and isoniazid despite limited availability of
      paediatric data on the pharmacokinetics of these drugs, especially from Africa,
      where the burden of childhood disease remains high. METHODS: Thirty children aged
      6 months to 15 years underwent intensive pharmacokinetic sampling for first-line
      anti-TB drugs at Queen Elizabeth Central Hospital, Blantyre, Malawi. Rifampicin,
      isoniazid, pyrazinamide and ethambutol were dosed at 10, 5, 25 and 20 mg/kg,
      respectively. Plasma drug concentrations were determined using sensitive,
      validated bioanalytical methods and summary pharmacokinetic parameters were
      estimated using non-compartmental analysis. RESULTS: The median (IQR) Cmax was
      2.90 (2.08-3.43), 3.37 (2.55-4.59), 34.60 (32.30-40.90) and 1.20 (0.85-1.68) mg/L
      while the median (IQR) AUC0-infinity was 16.92 (11.10-22.74), 11.48 (7.35-18.93),
      333.50 (279.50-487.2) and 8.65 (5.96-11.47) mg.h/L for rifampicin, isoniazid,
      pyrazinamide and ethambutol, respectively. For all drugs, pharmacokinetic
      parameters relating to drug absorption and exposure were lower than those
      published for adults, though similar to existing paediatric data from sub-Saharan
      Africa. Weight and/or dose predicted at least one measure of exposure for all
      drugs. Age-related decreases in CL/F for rifampicin and pyrazinamide and a
      biphasic elimination pattern of isoniazid were observed. Predicted AUC0 -infinity
      for rifampicin dosed at 15 mg/kg was comparable to that of adults while the dose
      required to achieve ethambutol exposure similar to that in adults was 55 mg/kg or
      higher. CONCLUSIONS: These data support recently revised WHO recommendations for
      dosing of anti-TB drugs in children, but dosing of ethambutol in children also
      appears inadequate by comparison with adult pharmacokinetic data.

PMID- 25759034
TI  - Survey of metallo-beta-lactamase-producing Enterobacteriaceae colonizing patients
      in European ICUs and rehabilitation units, 2008-11.
AB  - OBJECTIVES: The objective of this study was to perform a multinational survey of
      patients' colonization by metallo-beta-lactamase (MBL)-producing
      Enterobacteriaceae, including their molecular characterization. METHODS: Patients
      in 18 hospital units across Europe and Israel (n = 17 945) were screened between
      mid-2008 and mid-2011. MBL-producing isolates were typed by PFGE and MLST. MBL
      genes were amplified and sequenced within their integrons. Plasmids with MBL
      genes were analysed by nuclease S1 plus hybridization profiling, mating and
      transformation assays, and by PCR-based replicon typing. RESULTS: Ninety-one
      patients in nine centres (six countries), including 62 patients in two Greek
      ICUs, carried 94 non-duplicate MBL-producing organisms. Klebsiella pneumoniae
      isolates from Greece dominated (n = 57) and belonged mainly to ST147, ST36 and
      ST383. All but one of the isolates expressed VIM-1-type MBLs. Isolates of Greek
      origins produced five enzymes, including new VIM-39, encoded by class 1 integrons
      of four types. In-e541-like elements prevailed, comprising six variants located
      on IncR, IncFIIK, IncR + FIIK, IncR + A/C or non-typeable plasmids. The other
      group were new In4873 and In4863, being the first In416-like elements identified
      in Greece, which were present on IncA/C or non-typeable plasmids. Isolates from
      other countries produced only VIM-1 and the major integron was In916, identified
      in 16 organisms from France, Italy and Spain. In916 was carried by four plasmid
      types, including IncA/C, IncFIIK and IncHI2. Other integrons included a new
      element, In3103, in Spain and In110 identified only in Latvia. CONCLUSIONS: This
      study provided fully comparable data on the occurrence and molecular
      characteristics of VIM-producing Enterobacteriaceae in a group of hospital units
      across Europe, documenting recent changes in their epidemiology.

PMID- 25759037
TI  - [Outcome of the 6-year curriculum for pharmacy education: "Contribution to
      medical care and society: how will I act as a pharmacist in the future?"--A
      report on the 3rd National Student Workshop].
AB  - In August 2013, the Pharmaceutical Society of Japan held the Third National
      Student Workshop in Tokyo. A total of 88 people-70 sixth-year undergraduate
      students from 70 universities, and 18 alumni who had participated in the First
      and the Second Workshops-attended this Workshop. The theme of this Workshop was
      "Contribution to medical care and society: How will I act as a pharmacist in the
      future?" The first day took the form of a World Cafe, with participants
      exchanging information on such topics as, "The purpose for choosing a pharmacy
      major, and my achievement status", "My favorite aspects of my college", and "My
      dreams and paths: Painting my future image". Later that day, participants
      discussed and gave presentations on the ways they would be contributing as
      pharmacists to society and medical care. On the second day, participants
      discussed and gave presentations on the efforts they would like to make as
      pharmacists to contribute to society and medical care. The final session was a
      general assembly for discussion on the ways they would be contributing as
      pharmacists to society and medical care. Throughout the two days, attendees
      participated in discussions with an awareness of their common ground, in that
      they all had national qualification in spite of different intended paths. In this
      article, 4 sixth-year students (their status at the time of the symposium) from
      the Workshop introduce outlines of the discussions and products from each group.

PMID- 25759038
TI  - [Introduction of outcome-based education in pharmaceutical education in Japan].
AB  - Although Japanese medical and pharmaceutical educators have been interested in
      outcome-based education (OBE) in recent years, there are still many difficulties
      and problematic concepts involved in curriculum building, especially in
      determining objectives and assessment methods. From 2015, OBE will be
      incorporated in a model core curriculum of pharmaceutical education in Japan. In
      this paper, we will introduce the outline of an operative sample of OBE derived
      from the National Competency Standards Framework for Pharmacists in Australia.
      The products shown in this paper are examples of standards, elements, and some
      rubric scales and descriptors in the domain of "Practical ability in
      pharmaceutical therapy", as presented by the Ministry of Education, Culture,
      Sports, Science and Technology of Japan, and as proposed by many participants
      attending The Pharmaceutical Society of Japan's 3rd advanced workshop for
      pharmaceutical educators in 2013. We expect a helpful outline will enable each
      educational institution to design an appropriate OBE curriculum.

PMID- 25759039
TI  - [Design of spiral curriculum for pharmacy students to reach the outcome].
AB  - The third advanced workshop of the Pharmaceutical Society of Japan for
      pharmaceutical teachers was held from October 12th to 14th, 2013, and
      participants discussed an outcome-based approach to curriculum development in
      pharmacy education. In this article, I report the outcome-based spiral curriculum
      model of group 2A, which was designed to enable pharmacy students to understand a
      patient's condition, and to provide a basic practical ability in medical therapy.
      In the curriculum, pharmacy students will learn biochemistry and functional
      morphology in the first and second years, skills to interview patients in the
      third year, pathophysiology and pharmacotherapeutics in the third and fourth
      years, skills to estimate patient disease from physical examination in the fourth
      year, and practice in understanding real patient conditions in a clinical
      clerkship in the fifth year. The curriculum also included learning and evaluation
      methods.

PMID- 25759040
TI  - [Program to learn about the empowerment: diabetic theater, a workshop including
      drama and discussion].

PMID- 25759041
TI  - ["Throw your hammer!" The essence of patient empowerment in diabetes].
AB  - The empowerment approach to patients with diabetes is a philosophy that was
      introduced by Robert M. Anderson and Martha M. Funnell of Michigan Diabetes
      Research and Training Center in the 1990s. This approach is based on the
      observation that more than 98% of diabetes care is performed by patients
      themselves. Dr. Anderson, Ms. Funnell, and their colleagues found that every
      patient has a right and an ability to solve his/her own problem in his/her own
      diabetes. Therefore healthcare providers should provide support for patients own
      endeavors. Empowerment has three essential elements: 1) the patient is centered,
      they make a final decision of their daily self-management, and are responsible
      for those decisions and the results; 2) patient support is the main role of
      healthcare providers; and 3) patient and healthcare providers should collaborate.
      In this author's opinion, it is important for healthcare providers to improve
      their communication skills to use the empowerment approach to help patients
      change their behaviors in the real world. To encourage empowerment, we created a
      unique learning program for healthcare providers, named "Diabetes Theater". This
      program is an interactive workshop comprising two parts: drama and discussion.

PMID- 25759042
TI  - [Diabetes Theater in Kumamoto: scenario of the Diabetes Theater and contents of
      discussion].
AB  - Diabetes Theater (DT) is reenactment of pharmacists treating their patients
      during medical interviews. DT shows different pharmacists treating their patients
      using different methods. After the performance, the participants can learn from
      reflecting on the plays and their own work. At the 134th Annual Meeting of the
      Pharmaceutical Society of Japan, Kumamoto we performed 3 plays. The plays were
      about a diabetic patient with hypoglycemia who consults 3 pharmacists who have 3
      different approaches. Clinical pharmacists in Kumamoto performed and created DT.
      After DT, we received responses for each play from participants. Some
      participants stated that it is necessary for pharmacists to respect patients'
      feelings and that pharmacists should speak to patients in layman's terms.
      Participants generally understood the purpose of DT. Some participants said that
      they do not have enough time to console patients. Pharmacists who performed as
      patients said that they were better able to see from the patients' point of view
      during medical interviews.

PMID- 25759043
TI  - [Evaluation of Diabetes Theater: results of questionnaire survey and discussion].
AB  - We started Diabetes Theater (DT), a program for medical staff, with a short drama
      and discussion with attendees in 2009. The program has two parts. One is a short
      drama enacting realistic scenes between medical staff and patients. After that,
      facilitators prompt responses from the audience. The basic concept of the program
      is empowerment for patients: a process of empowerment in terms of discovery and
      development of one's own life. People are empowered when they have sufficient
      knowledge to make rational decisions, sufficient control and resources to
      implement their decisions, and sufficient experience to evaluate the
      effectiveness of their decisions. We performed DT at the Annual Meeting of the
      Pharmaceutical Society of Japan, Kumamoto. Thereafter, we researched the positive
      educational effects of the program by issuing a questionnaire; the results are
      presented herein, along with some of our views on the benefits of a drama program
      on pharmacist training and undergraduate education. The total number of
      respondents was 78 (M/F, 40/38). Hospital pharmacists comprised 38%; students
      26%; academia 19%; community pharmacists 9%; and others 8%. In conclusion, DT was
      well accepted by attendances as a unique program to learn effective patient
      communication skills and thereby achieve better patient-pharmacist relations. Our
      findings suggest that DT might be an interesting approach to improve attitudes of
      pharmacists in diabetes care with the aim of empowerment.

PMID- 25759044
TI  - [In what ways can we expand on empowerment to pharmacists?].
AB  - The number of Japanese patients with chronic diseases is increasing year by year
      largely because of the acceleration of demographic aging and lifestyle changes in
      Japan. Although many patients with chronic diseases receive their medications
      from pharmacists, many community pharmacists have not changed their communication
      style with their patients. Empowerment is the basic idea that patient support is
      not widely known by pharmacists but the certified diabetes educator (CDE). We
      started Diabetes Theater, a program for healthcare providers that includes short
      drama and discussion with attendees, in 2009. The concept of the program is
      empowerment for patients: a process to help patients make better healthcare
      decisions. In addition, we launched another educational program to help community
      pharmacists learn about communication skills with diabetes patients named "The
      Three star Pharmacist Training Program" in 2012. In this article, we discuss our
      forthcoming plans to spread these ideas of empowerment among pharmacists.

PMID- 25759045
TI  - [Chemical biology for pharmaceutical science--integrative approaches for
      elucidation of biological phenomena].

PMID- 25759046
TI  - [Creation of artificial receptors activated by coiled-coil peptides and cellular
      regulation].
AB  - Exploiting the ability of coiled-coil peptides to induce dimer formation, we
      designed an artificial epidermal growth factor receptor (EGFR) in which
      dimerization is essential for increasing the tyrosine kinase activity of its
      intracellular domain. Using leucine-zipper coiled-coil peptides, the surface
      exposed E3 ((EIAALEK)3) tag sequence was fused with EGFR (E3-EGFR) lacking
      domains I-III and a part of IV, which participate in dimerization of EGFR after
      binding to natural ligand (that is, epidermal growth factor). To dimerize E3-EGFR
      we synthesized conjugates of two K4 ((KIAALKE)4) peptides, called K4-conjugates,
      with linker lengths approximately 10 angstrom that mimic the distance of EGFR
      dimerization. Receptor phosphorylation of E3-EGFR was found to increase within 5
      min in CHO cells expressing E3-EGFR after treatment with K4 conjugates. Increased
      lamellipodia formation and migration of the cells was also observed when treated
      with the artificial ligands. This receptor model can be applied to a wide variety
      of membrane-associated proteins to control cellular processes and to elucidate
      the functional mechanisms of these proteins using chemical biology.

PMID- 25759047
TI  - [Total synthesis of biologically active alkaloids using bio-inspired indole
      oxidation].
AB  - Many tryptophan-based dimeric diketopiperazine (DKP) alkaloids including WIN
      64821 and ditryptophenaline, which exhibit fascinating biological activities,
      have been isolated from fungi. These alkaloids possess a unique architecture;
      therefore several total syntheses of these compounds have been accomplished via
      bio-inspired reactions. Despite these elegant strategies, we were convinced that
      a more direct bio-inspired solution for the preparation of tryptophan-based DKP
      alkaloids was possible because in a true biosynthesis, direct dimerization of
      tryptophan occurs in aqueous media without incorporation of a protecting group on
      the substrates. Thus we developed direct bio-inspired dimerization reactions in
      aqueous, acidic media, along with a novel biomimetic pathway, to provide C2
      symmetric and non-symmetric dimeric compounds from commercially available amine
      free tryptophan derivatives using Mn(OAc)3, VOF3, and V2O5 as one-electron
      oxidants. In addition, concise two-pot or three-step syntheses of the naturally
      occurring dimeric DKP alkaloids (+)-WIN 64821, (-)-ditryptophenaline, and (+)
      naseseazine B were accomplished with total yields of 20%, 13%, and 20%,
      respectively. The present synthesis has several noteworthy features: 1) the
      tryptophan-based C2-symmetric and non-symmetric dimeric key intermediates can be
      prepared on a multigram scale in one step; 2) the developed oxidation reaction
      was carried out in aqueous, acidic solution without deactivation of the metal
      oxidants; 3) protection of the primary amine can be avoided by salt formation in
      aqueous acid; 4) for the total two-pot operation, the reaction media are
      environmentally friendly water and ethanol; 5) satisfactory total yields are
      obtained compared with previously reported syntheses.

PMID- 25759048
TI  - [Non-invasive analysis of proteins in living cells using NMR spectroscopy].
AB  - NMR spectroscopy enables structural analyses of proteins and has been widely used
      in the structural biology field in recent decades. NMR spectroscopy can be
      applied to proteins inside living cells, allowing characterization of their
      structures and dynamics in intracellular environments. The simplest "in-cell NMR"
      approach employs bacterial cells; in this approach, live Escherichia coli cells
      overexpressing a specific protein are subjected to NMR. The cells are grown in an
      NMR active isotope-enriched medium to ensure that the overexpressed proteins are
      labeled with the stable isotopes. Thus the obtained NMR spectra, which are
      derived from labeled proteins, contain atomic-level information about the
      structure and dynamics of the proteins. Recent progress enables us to work with
      higher eukaryotic cells such as HeLa and HEK293 cells, for which a number of
      techniques have been developed to achieve isotope labeling of the specific target
      protein. In this review, we describe successful use of electroporation for in
      cell NMR. In addition, (19)F-NMR to characterize protein-ligand interactions in
      cells is presented. Because (19)F nuclei rarely exist in natural cells, when
      (19)F-labeled proteins are delivered into cells and (19)F-NMR signals are
      observed, one can safely ascertain that these signals originate from the
      delivered proteins and not other molecules.

PMID- 25759049
TI  - [Synthetic RNA technologies to control functions of mammalian cells].
AB  - We recently succeeded in producing nanostructures made of RNA-protein (RNP)
      complexes. We show that RNA and the ribosomal protein L7Ae can form a triangular
      like nanostructure that consists of three L7Ae proteins, which form the apices of
      the triangle, bound to one RNA scaffold. This shape is created through a 60
      degrees  kink introduced into the RNA structure on L7Ae binding. By varying the
      size of the RNA scaffold we could in turn alter the overall size of the
      triangular nanostructure. Several functions can be added to this nanostructure by
      the introduction of effector proteins fused to L7Ae. The design and construction
      of functional RNP nanostructures that detect specific cancer cells are discussed
      herein. In parallel, we developed synthetic RNP translational switches to control
      production levels of particular proteins depending on certain input(s) within the
      intracellular environment. The RNP-binding module was successfully incorporated
      into mRNA to generate functional RNP switches. The designed ON/OFF translational
      switches detect expression of the trigger factor and repress or activate
      expression of a desired protein (e.g., apoptosis regulator) in target mammalian
      cells. Taken together, RNP-binding module could be employed for constructing
      designer genetic switches and functional nanostructures to regulate cellular
      processes.

PMID- 25759050
TI  - [Application and potential of genome engineering by artificial enzymes].
AB  - Artificial zinc finger proteins (ZFPs) consist of Cys2-His2-type modules composed
      of approximately 30 amino acids that adopt a betabetaalpha structure and
      coordinate a zinc ion. ZFPs recognizing specific DNA target sequences can
      substitute for the binding domains of various DNA-modifying enzymes to create
      designer nucleases, recombinases, and methylases with programmable sequence
      specificity. Enzymatic genome editing and modification can be applied to many
      fields of basic research and medicine. The recent development of new platforms
      using transcription activator-like effector (TALE) proteins or the clustered
      regularly interspaced short palindromic repeats/CRISPR-associated protein
      (CRISPR/Cas) system has expanded the range of possibilities for genome-editing
      technologies. These technologies empower investigators with the ability to
      efficiently knockout or regulate the functions of genes of interest. In this
      review, we discuss historical advancements in artificial ZFP applications and
      important issues that may influence the future of genome editing and engineering
      technologies. The development of artificial ZFPs has greatly increased the
      feasibility of manipulating endogenous gene functions through transcriptional
      control and gene modification. Advances in the ZFP, TALE, and CRISPR/Cas
      platforms have paved the way for the next generation of genome engineering
      approaches. Perspectives for the future of genome engineering are also discussed,
      including applications of targeting specific genomic alleles and studies in
      synthetic biology.

PMID- 25759051
TI  - [Development and application of electroanalytical methods in biomedical fields].
AB  - To summarize our electroanalytical research in the biomedical field over the past
      43 years, this review describes studies on specular reflection measurement, redox
      potential determination, amperometric acid sensing, HPLC with electrochemical
      detection, and potential oscillation across a liquid membrane. The specular
      reflection method was used for clarifying the adsorption of neurotransmitters and
      their related drugs onto a gold electrode and the interaction between dental
      alloys and compound iodine glycerin. A voltammetric screening test using a redox
      potential for the antioxidative effect of flavonoids was proposed. Amperometric
      acid sensing based on the measurement of the reduction prepeak current of 2
      methyl-1,4-naphthoquinone (VK3) or 3,5-di-tert-buty1-1,2-benzoquinone (DBBQ) was
      applied to determine acid values of fats and oils, titrable acidity of coffee,
      and enzyme activity of lipase, free fatty acids (FFAs) in serum, short-chain
      fatty acids in feces, etc. The electrode reactions of phenothiazines, catechins,
      and cholesterol were applied to biomedical analysis using HPLC with
      electrochemical detection. A three-channel electrochemical detection system was
      utilized for the sensitive determination of redox compounds in Chinese herbal
      medicines. The behavior of barbituric acid derivatives was examined based on
      potential oscillation measurements.

PMID- 25759052
TI  - [Study of cytokine signaling: the quest for immunomodulatory drugs interacting
      with cytokine production and activity].
AB  - I have been engaged in research and education in the fields of immunology and
      biochemistry at a medical college and college of pharmacy for 40 years. The
      original reasons why I began studying cytokines and some of the interests that
      have motivated me to continue working in the field of cytokine research are
      described: 1) the roles of cytokines in various immunological and inflammatory
      diseases (e.g., chemokines in bacterial infections and inflammatory diseases,
      particularly the role of interleukin-5 and eotaxins in eosinophilia); 2) the role
      of focal adhesion kinase in antiapoptosis and metastasis of melanoma; 3) recent
      findings on the role of JAK2/STAT pathways, particularly how JAK2V617F mutation
      induces dysregulated proliferation and tumorigenesis; and 4) the interactions of
      various chemical compounds and natural products in cytokine gene activation and
      signaling. Previous discoveries and published findings by my research group are
      described, along with comments and discussion pertaining to recent developments
      in the field.

PMID- 25759053
TI  - [A new strategy for preventive and functional therapeutic methods for dementia-
      approach using natural products].
AB  - Alzheimer's disease (AD) has become a serious social problem in Japan. However,
      effective preventive and fundamental therapeutic methods for AD have not yet been
      developed. Using a new strategy in the course of our survey of numerous natural
      resouces having neurotrophic activity, we isolated a variety of active
      constituents and proved their pharmacological properties. As a result, we
      successfully found nobiletin, a compound with anti-dementia activity that comes
      from citrus peels. Also, we have demonstrated that nobiletin ameliorates
      cognitive impairment in several dementia model animals such as chronically
      amyloid beta(Abeta) infused rats, amyloid precursor protein transgenic (APPTg)
      mice, olfactory-bulbectomized (OBX) mice, N-methyl-D-aspartate (NMDA) receptor
      antagonist (MK-801)-treated mice, senescence-accelated mice and bilaterial common
      carotid arteries occlusion mice. In a APPTg mouse of AD, nobiletin greatly
      improved memory impairment, and this was accompanied by a marked decrease in
      Abeta deposition. Also, in OBX mice memory impairment was markedly recoverd by
      nobiletin, accompanied by improvement of a decrease indensity of cholinergic
      neurons. Interestingly, nobiletin improves age-related congnitive impairment and
      decreased hyperphosphorylation of tau as well as oxidative stress in senescence
      accelerated mice. In cultured cells, nobiletin reversed the Abeta-induced
      inhibition of glutamate-induced increases in cAMP response element binding
      protein (CREB) phosphorylation and modulated gen expression of thioredoxin
      interacting protein and NMDA resceptor subunits. These results suggest that
      nobiletin prevents memory impairment and exhibits a protecting action against
      neurodgeneration in AD model animals. Nobiletin and citrus peels thus have
      potential as functional foods for prevention of dementia.

PMID- 25759054
TI  - [Pharmacological study and pharmaceutical intervention to reduce intravenous
      injection-induced vascular injury].
AB  - Intravenous injection often causes vascular injury such as venous irritation,
      vascular pain, and phlebitis. Vascular injury deteriorates the patient's QOL and
      sometimes limits the continuation of injection therapy. Pharmaceutical
      intervention and pharmacological mechanisms used to reduce vascular injury
      induced by vinorelbine and epirubicin were reviewed. A multivariate logistic
      regression analysis revealed that the dose of vinorelbine (>=40 mg) was a
      significant predictor for venous irritation. Alteration of the volume of normal
      saline for vinorelbine dissolution, from 50 to 100 mL, significantly decreased
      the grade of venous irritation. On the other hand, the phlebitis scores were
      significantly higher in patients treated with epirubicin ready-to-use solution
      compared with lyophilized powder. The change of formulation of epirubicin to
      lyophilized powder decreased the risk of venous irritation. The concentration
      inducing 50% cell viability inhibition was lower in the order of vesicant,
      irritant, and nonvesicant drugs on porcine aorta endothelial cells (PAECs),
      suggesting that the injuring effects of anticancer drugs on PAECs may be relevant
      as an indicator of the frequency of their vascular injury. The exposure to
      vinorelbine of PAECs rapidly depleted intracellular glutathione levels and
      increased intracellular reactive oxygen species production. Moreover, exposure to
      epirubicin increased intracellular lipid peroxide levels and enhanced the
      phosphorylation of p38 mitogen-activated protein kinase. These results
      demonstrate that oxidative stress plays an important role in vinorelbine- and
      epirubicin-induced endothelial cell injury, and may therefore increase the
      potential for vascular injury upon intravenous injection.

PMID- 25759055
TI  - [Determinants of the stereoselective pharmacokinetics of fexofenadine].
AB  - Drug transporters play an important role in the clinical pharmacokinetics of many
      therapeutic agents. Although it is estimated that about half of all therapeutic
      agents are chiral, there has been little information on the stereoselective
      pharmacokinetics related to drug transporters. This review focuses on the drug
      transporters contributing to the stereoselective pharmacokinetics of fexofenadine
      enantiomers in humans. Fexofenadine is administered clinically as a racemic
      mixture, and the plasma concentration of (R)-fexofenadine is about 1.5-fold
      higher than that of the (S)-enantiomer. Because fexofenadine is poorly
      metabolized by cytochrome P450s, its pharmacokinetics depends on its drug
      transporter activities. First, we examined whether drug-transporter polymorphisms
      influence fexofenadine enantiomer pharmacokinetics. The findings suggested that a
      combination of multiple transporters involving organic anion transporting
      polypeptide (OATP) 2B1, P-glycoprotein (P-gp), and multidrug resistance
      associated protein 2 (MRP2) react to stereoselective fexofenadine exposure.
      Subsequently, we evaluated the roles of P-gp and OATPs in fexofenadine enantiomer
      pharmacokinetics using these inducer/inhibitors. Coadministration of P-gp
      inducer/inhibitors significantly altered the pharmacokinetics of fexofenadine
      enantiomers. In addition, the OATP inhibitors rifampicin and apple juice also
      affected fexofenadine enantiomer pharmacokinetics. Moreover, in in vitro studies,
      the uptake of both fexofenadine enantiomers into OATP2B1 cRNA-injected oocytes
      was significantly higher than that into water-injected oocytes, and this effect
      was greater for (R)-fexofenadine. Taken together, these studies indicated that
      multiple transporters including P-gp, OATPs, and MRP2 play important roles in
      fexofenadine enantiomer pharmacokinetics. Furthermore, OATP2B1 is a key
      determinant of the stereoselective pharmacokinetics of fexofenadine, and drug
      transporters may have chiral discrimination ability.

PMID- 25759056
TI  - [Rab GTPases networks in membrane traffic in Saccharomyces cerevisiae].
AB  - Intracellular membrane trafficking between membranous compartments is essential
      for organelle biogenesis, structure, and identity. Rab/Ypt GTPases are well
      characterized regulators of intracellular membrane trafficking, functioning as
      molecular switches that alternate between GTP- and GDP-bound forms. In
      Saccharomyces cerevisiae, 11 Rab/Ypt GTPases have been identified and their
      functions are known to be conserved in their mammalian counterparts. In yeast,
      the secretory pathway is regulated by sequential activation and inactivation (the
      so-called Rab cascade) of three types of yeast Rab protein -Ypt1p, Ypt31p/32p and
      Sec4p -via specific guanine nucleotide exchange factors (GEFs) and GTPase
      activating proteins (GAPs). In addition to these Rabs, we and others have
      recently demonstrated that Ypt6p is predominantly localized to the early Golgi
      compartment, and functions as another regulator of anterograde transport for
      intra-Golgi trafficking in the secretory pathway. On the other hand, the
      endocytic pathway is known to be regulated by three yeast Rab5s (Vps21p, Ypt52p
      and Ypt53p) and one Rab7 (Ypt7p). Rab5 and Rab7 are key determinants of endosome
      identity, and the Rab5-Rab7 cascade is important for the progression from early
      to late endosome. Our recent study demonstrates that the endocytic pathway
      branches into two vacuolar targeting pathways, the Rab5-dependent vacuole protein
      sorting (VPS) pathway and the Rab5-independent pathway. In this review, we focus
      on recent advances in our understanding of molecular mechanisms that regulate the
      localization and activity of yeast Rab GTPases in intracellular membrane
      trafficking.

PMID- 25759057
TI  - [Development of a therapeutic agent for Menkes disease: solubilization of a
      copper-disulfiram complex].
AB  - Menkes disease (MD) is a neurodegenerative disorder characterized by copper
      deficiency. It is caused by defective intestinal absorption of copper resulting
      from a deficiency of a copper-transporting ATPase, ATP7A. We investigated the
      effects of combination therapy with copper and disulfiram, a known lipophilic
      chelator. We synthesized a copper-disulfiram complex (Cu-DSF) and determined its
      crystal structure by X-ray crystallographic analysis. Unfortunately, Cu-DSF was
      not orally bioavailable due to its lipophilicity. We therefore planned to use
      cyclodextrin as a solubilizing agent to increase the water solubility of Cu-DSF.
      After comparisons of the effects of cyclodextrins (alpha, beta, gamma), it was
      found that addition of beta-cyclodextrin (beta-CyD) increased the solubility of
      Cu-DSF. Moreover, the modified beta-CyD, hydroxypropyl-beta-cyclodextrin, was yet
      more effective as a solubilizing agent. For the development of a convenient
      method to determine the concentration of Cu-DSF included by beta-cyclodextrins, a
      standard curve based on UV-visible(VIS) absorption was derived.

PMID- 25759058
TI  - [A systematic review of decided litigated cases on adverse drug events in Japan:
      classification of decided cases appearing in law reports].
AB  - Much of the damage to health caused by drugs could be prevented by appropriate
      care. A well-defined duty of care and further information are required for
      healthcare professionals. Although there are many litigation cases to use as
      references, neither the extent of the duty of care nor the obligation to explain
      medication according to the type of drug prescribed has yet been fully
      established. Thus, we systematically collected decided cases of adverse drug
      events, and assessed the degree of the duties of care and information.
      Specifically, we collected decided cases in which physicians, dentists,
      pharmacists, nurses, or hospitals had been sued. Data were derived from Bessatsu
      Jurist Iryo-kago Hanrei Hyakusen, Hanrei Jihou, and Hanrei Times from 1989 to
      November 2013, and information on precedents in the records of the Supreme Court
      of Japan from 2001 to November 2013. We analyzed the cases, and assessed the
      following according to the type of drug: (1) standards and explanations when
      dealing with drugs that were critical issues in litigation, and (2) the degree of
      the physician's or pharmacist's duties of care and information. In total, 126
      cases were collected. The number of drug categories classified was 27, and 9 were
      considered of practical importance. After this systematic review, we found a
      trend in the degree of the required level of care and information on several
      drugs. With respect to duties of care and information, the gap between the
      required level and actual practice suggests that healthcare professionals must
      improve their care and explanations.

PMID- 25759059
TI  - [Practical program to gather patient information from a diversified perspective
      and provide appropriate therapies in practical hospital training].
AB  - In the 11-week practical hospital training of pharmaceutical students in Nagoya
      University Hospital, a clinical practice program has been implemented with the
      objective of compensating for any deficits students may have in skills and
      attitudes due to insufficiencies in their formal education. The program aims to
      enable the students to observe patients from various angles, obtain from them
      information necessary for drug therapy, and propose multiple treatment methods
      according to the patient's background and situation. Tests are conducted before
      and after the program to assess the students' knowledge and to confirm whether
      lectures on basic knowledge of practical skills had been provided and whether
      practical skill training had been performed. The rate of correct answers on the
      postprogram test rose significantly after the practice program compared with the
      preprogram scores, thus confirming that the students' knowledge improved. Because
      the content of their knowledge and the experience that they had acquired
      previously was in accordance with older guidelines, however, it will be necessary
      to update students' knowledge regularly and to instill knowledge, skills, and
      attitudes that they will be able to apply in actual medical practice. In the
      questionnaire after the end of the program, more than 80% of the students
      indicated that they had benefitted. Many responded that this program would be
      useful for their practical hospital training on the wards and for their future
      work. This suggests that the program is extremely beneficial to the students.

PMID- 25759060
TI  - [Nationwide study on relations between workload and outcomes of home visiting
      service by community pharmacists].
AB  - A nationwide survey was conducted to verify relations between the workload of
      home-visiting service by community pharmacists and outcomes. Data were collected
      on 5447 patients from 1890 pharmacies. Most (61.9%) pharmacists visited patients'
      homes twice monthly, spending there a net average of 20.6 work minutes. At the
      time of the survey, 29.8% of the patients had improvement of adherence compared
      with at start of home visits; 65.5% had no change, and 1.4% had gotten worse.
      Similarly, 41.6% had decreased unused medications, 54.4% had no change, and 2.3%
      had increased. Home-visiting pharmacists found adverse drug events (ADEs) caused
      by drug administration in 14.4% of their patients. They dealt with 44.2% of these
      cases by discontinuing administration of the responsible drug, 24.5% by reducing
      the dosage, and 18.3% by changing drugs, with a total of 88.1% having been
      improved. Prescription changes intended to correct problems occurred in 37.1% of
      the patients. In patients whom the pharmacists visited more often, a higher
      percent had ADEs, had their prescription changed to correct problems, and had
      improved adherence and unused medications. The average actual work time was
      longer in patients whose outcomes improved than in those whose outcomes did not.
      A higher involvement in homecare by pharmacists was found to improve outcomes of
      drug treatment.

PMID- 25759061
TI  - [Current status of illegal trade in pharmaceutical products on Internet auction
      sites in Japan and responses of site administrators to such transactions].
AB  - In Japan, it is illegal to sell pharmaceuticals on Internet auction sites,
      although a considerable number of pharmaceuticals are listed on such sites. We
      investigated the current situation regarding the illegal trade in pharmaceuticals
      on Japanese Internet auction sites and the responses of site administrators to
      such transactions. We searched for pharmaceuticals and "gray" items that were
      suspected of being pharmaceuticals on Yahoo-oku! (Yahoo! Auctions, Japan) over a
      37-day period and then submitted violation reports indicating that selling
      pharmaceuticals is illegal or that the description of an item was insufficient.
      The reports were directed to the site administrators and forwarded to the
      sellers. One hundred and six pharmaceutical products and 34 gray items were
      identified during the study period. After the submission of the violation
      reports, only 28 of the pharmaceutical products and one of the gray items were
      deleted by the administrator, while 18 of the pharmaceutical products and 7 of
      the gray items were withdrawn by their sellers. However, 41 pharmaceuticals and
      20 gray items were sold. Most of the gray items were listed using characteristic
      terms or abbreviations without photographic images. More than 70% of the
      identified pharmaceuticals had a contraindication(s) other than hypersensitivity.
      In conclusion, the illegal trade in pharmaceuticals on Internet auction sites
      remains a serious problem in Japan, and the responses of site administrators to
      such transactions are inadequate. The government and pharmaceutical industry may
      have to take measures such as providing public and administrative guidance to
      stop the illegal trade in pharmaceuticals on the Internet.

PMID- 25759062
TI  - [Evaluation of an on-site drug-testing device for the detection of synthetic
      cannabinoids in illegal herbal products].
AB  - Recently, illegal herbal or liquid products containing psychoactive compounds
      have been a serious problem damaging human health and causing numerous traffic
      accidents. Reports indicate that most of those herbal products contain various
      types of synthetic cannabinoids. There are many on-site drug-testing devices;
      however, synthetic cannabinoids are not targeted compounds for such devices. In
      this study, we evaluated the on-site drug-testing device "K2/Spice Test" for the
      detection of 12 different types of 38 synthetic cannabinoids (including 13
      naphthoylindole-type synthetic cannabinoids) and a natural cannabinoid (Delta(9)
      tetrahydrocannabinol). Although this device is primarily used for the detection
      of metabolites of naphthoylindole-type synthetic cannabinoids in urine samples,
      we applied it to detect synthetic cannabinoids in illegal herbal products for
      rapid screening analyses. As a result of the on-site examination of synthetic
      cannabinoids, 10 naphthoylindole-type synthetic cannabinoids [five narcotics (JWH
      018, JWH-073, AM-2201, MAM-2201, and JWH-122); five designated substances (JWH
      015, JWH-200, AM-1220, JWH-019, and JWH-020)], and two other types of synthetic
      cannabinoid [designated substances (a benzoylindole AM-694 and a
      naphthoylnaphthalene CB-13)] showed positive results (the limit of detection
      ranged from 50 to 250 MUg/mL). Furthermore, MeOH extracts of illegal herbal
      products containing naphthoylindole-type synthetic cannabinoids also showed
      positive results (the limit of detection ranged from 2.5 to 10 mg herbal
      products/mL). Therefore, we found that this device may be useful for the on-site
      examination of some naphthoylindole-type synthetic cannabinoids not only in urine
      samples but also in illegal herbal products.

PMID- 25759063
TI  - Toward automated classification of consumers' cancer-related questions with a new
      taxonomy of expected answer types.
AB  - This article examines methods for automated question classification applied to
      cancer-related questions that people have asked on the web. This work is part of
      a broader effort to provide automated question answering for health education. We
      created a new corpus of consumer-health questions related to cancer and a new
      taxonomy for those questions. We then compared the effectiveness of different
      statistical methods for developing classifiers, including weighted classification
      and resampling. Basic methods for building classifiers were limited by the high
      variability in the natural distribution of questions and typical refinement
      approaches of feature selection and merging categories achieved only small
      improvements to classifier accuracy. Best performance was achieved using weighted
      classification and resampling methods, the latter yielding an accuracy of F1 =
      0.963. Thus, it would appear that statistical classifiers can be trained on
      natural data, but only if natural distributions of classes are smoothed. Such
      classifiers would be useful for automated question answering, for enriching web
      based content, or assisting clinical professionals to answer questions.

PMID- 25759064
TI  - Specific factors influencing information system/information and communication
      technology sourcing strategies in healthcare facilities.
AB  - Healthcare facilities use a number of information system/information and
      communication technologies. Each healthcare facility faces a need to choose
      sourcing strategies most suitable to ensure provision of information
      system/information and communication technology services, processes and
      resources. Currently, it is possible to observe an expansion of sourcing
      possibilities in healthcare informatics, which creates new requirements for
      sourcing strategies. Thus, the aim of this article is to identify factors
      influencing information system/information and communication technology sourcing
      strategies in healthcare facilities. The identification was based on qualitative
      research, namely, a case study. This study provides a set of internal and
      external factors with their impact levels. The findings also show that not enough
      attention is paid to these factors during decision-making.

PMID- 25759065
TI  - SENHANCE: A Semantic Web framework for integrating social and hardware sensors in
      e-Health.
AB  - Self-reported data are very important in Healthcare, especially when combined
      with data from sensors. Social Networking Sites, such as Facebook, are a
      promising source of not only self-reported data but also social data, which are
      otherwise difficult to obtain. Due to their unstructured nature, providing
      information that is meaningful to health professionals from this source is a
      daunting task. To this end, we employ Social Network Applications as Social
      Sensors that gather structured data and use Semantic Web technologies to fuse
      them with hardware sensor data, effectively integrating both sources. We show
      that this combination of social and hardware sensor observations creates a novel
      space that can be used for a variety of feature-rich e-Health applications. We
      present the design of our prototype framework, SENHANCE, and our findings from
      its pilot application in the NutriHeAl project, where a Facebook app is
      integrated with Fitbit digital pedometers for Lifestyle monitoring.

PMID- 25759066
TI  - How can we get better at providing patient centred care: does continuity matter?

PMID- 25759067
TI  - The role of high-density lipoproteins in the regulation of angiogenesis.
AB  - Angiogenesis is important for postnatal physiological processes including tissue
      neovascularization in response to an ischaemic injury. Conversely, uncontrolled
      inflammatory-driven angiogenesis can accelerate atherosclerotic plaque and tumour
      growth. Angiogenesis-associated diseases are highly prevalent globally, with
      cardiovascular-related disorders and cancer being the leading causes of mortality
      worldwide. A vast amount of research has been conducted on the vasculoprotective
      effects of high-density lipoproteins (HDLs) and while current HDL-raising
      therapies to date have not yielded the desired benefits clinically, its role in
      angiogenesis is yet to be fully elucidated. Epidemiological studies report
      positive correlations between elevated HDL levels and improved prognosis in both
      ischaemia- and inflammatory-driven pathologies, in which angiogenesis plays a key
      role. This review focuses on current evidence from epidemiological and
      prospective studies, coupled with animal models and mechanistic studies that
      highlight the ability of HDL to conditionally regulate angiogenesis. 

PMID- 25759068
TI  - Professor Arlette Darfeuille-Michaud: the discovery of adherent-invasive
      Escherichia coli.

PMID- 25759069
TI  - Ageing workers with work-related musculoskeletal injuries.
AB  - BACKGROUND: Older workers often take longer to recover and experience more missed
      workdays after work-related injuries, but it is unclear why or how best to
      intervene. Knowing the characteristics of older injured workers may help in
      developing interventions to reduce the likelihood of work disability. AIMS: To
      describe and compare several characteristics between younger and middle-aged
      working adults (25-54 years), adults nearing retirement (55-64 years) and adults
      past typical retirement (>=65 years), who sustained work-related musculoskeletal
      injuries. METHODS: In this cross-sectional study, Alberta workers' compensation
      claimants with subacute and chronic work-related musculoskeletal injuries were
      studied. A wide range of demographic, employment, injury and clinical
      characteristics were investigated. Descriptive statistics were computed and
      compared between the age groups. RESULTS: Among 8003 claimants, adults 65 years
      or older, compared to those 25-54 and 55-64 years, had lower education (16 versus
      10 and 12%, P < 0.001) and were more likely to work in trades, transport and
      related occupations (50 versus 46 and 44%, P < 0.001), to have less offers of
      modified work (57 versus 39 and 42%, P < 0.001), more fractures (18 versus 14 and
      11%, P < 0.001) and no further rehabilitation recommended after assessment (28
      versus 18 and 20%, P < 0.01). CONCLUSIONS: Injured workers past typical
      retirement age appeared to be a disadvantaged group with significant challenges
      from a vocational rehabilitation perspective. They were less likely to have
      modified work options available or be offered rehabilitation, despite having more
      severe injuries.

PMID- 25759070
TI  - Noise-induced hearing loss and combined noise and vibration exposure.
AB  - BACKGROUND: While there is a wide body of literature addressing noise-induced
      hearing loss (NIHL) and hand-arm vibration syndrome (HAVS) independently,
      relatively few studies have considered the combined effects of noise and
      vibration. These studies have suggested an increased risk of NIHL in workers with
      vibration white finger (VWF), though the relationship remains poorly understood.
      AIMS: To determine whether hearing impairment is worse in noise-exposed workers
      with VWF than in workers with similar noise exposures but without VWF. METHODS:
      The Quebec National Institute of Public Health audiometric database was used in
      conjunction with work-related accident and occupational diseases data from the
      Quebec workers' compensation board to analyse differences in audiometry results
      between vibration-exposed workers in the mining and forestry industries and the
      overall source population, and between mining and forestry workers with
      documented VWF and those without VWF. The International Organization for
      Standardization (ISO) 7029 standards were used to calculate hearing loss not
      attributable to age. RESULTS: 15751 vibration-exposed workers were identified in
      an overall source population of 59339. Workers with VWF (n = 96) had
      significantly worse hearing at every frequency studied (500, 1000, 2000 4000 Hz)
      compared with other mining and forestry workers without VWF. CONCLUSIONS: This
      study confirms previous findings of greater hearing loss at higher frequencies in
      workers with VWF, but also found a significant difference in hearing loss at low
      frequencies. It therefore supports the association between combined noise and
      hand-arm vibration (HAV) exposure and NIHL.

PMID- 25759071
TI  - Cranial neural crest deletion of VEGFa causes cleft palate with aberrant vascular
      and bone development.
AB  - Cleft palate is among the most common craniofacial congenital anomalies. Up to
      30% of patients with cleft palate also have associated cardiac and vascular
      defects. VEGFa, a critical growth factor involved in multiple developmental
      processes including angiogenesis and ossification, is also required for palate
      development. Conditional deletion of VEGFa in cranial neural crest (CNC) cells
      using Wnt1-Cre (VEGFaCKO) resulted in cleft palate in mice. The phenotype
      included reduced proliferation of cells within the palatal shelves, abnormal
      palatal shelf elongation and elevation, and the inability to undergo fusion.
      Vascularization of the VEGFaCKO palatal shelves was greatly reduced, suggesting a
      non-cell autonomous role of VEGFa signaling from the CNC-derived cells to the
      endothelium during vessel formation. Defective vascular development was coupled
      with deficient intramembranous ossification of maxillary and palatal mesenchyme.
      In vitro assessment of CNC-derived palatal mesenchymal cells from VEGFaCKO mice
      demonstrated normal ossification after BMP2 stimulation, suggesting that
      inadequate expression of Bmp2 in VEGFaCKO mice was, in part, responsible for
      reduced ossification. Taken together, these data demonstrate that VEGFa produced
      in the CNC-derived mesenchyme drives proliferation, vascularization, and
      ossification, all of which are critical for palate development.

PMID- 25759072
TI  - Differential distribution of probenecid as detected by on-tissue mass
      spectrometry.
AB  - We demonstrate, by means of on-tissue mass spectrometry of tissue sections, that
      the drug probenecid can penetrate the blood-brain barrier. This method holds
      general promise for the detection and distribution of small molecule drugs within
      organ and tissue compartments. 

PMID- 25759073
TI  - Erratum to: The guanine nucleotide exchange factor Vav3 regulates differentiation
      of progenitor cells in the developing mouse retina.

PMID- 25759074
TI  - Four factors predict persistent abdominal pain in children, study finds.

PMID- 25759075
TI  - Distal pancreatic resection for neuroendocrine tumors: is laparoscopic really
      better than open?
AB  - BACKGROUND: The latest studies on surgical and cost-analysis outcomes after
      laparoscopic distal pancreatectomy (LDP) highlight mixed and insufficient
      results. Whereas several investigators have compared surgical outcomes of LDP vs.
      open distal pancreatectomy (ODP) for adenocarcinomas, few similar studies have
      focused on pancreatic neuroendocrine tumors (PNETs). METHODS: We reviewed the
      medical records of PNET patients undergoing distal pancreatectomy between 2004
      and 2014. Patients were divided into LDP vs. ODP groups. Demographics, relevant
      comorbidities, oncologic variables, and cost-analysis data were assessed.
      Survival and Cox proportional hazards analyses were used to evaluate outcomes.
      RESULTS: Of the 171 distal pancreatectomies for PNETs, 73 were laparoscopic,
      whereas 98 were open. Patients undergoing LDP demonstrated significantly lower
      rates of postoperative complications (P=0.028) and had significantly shorter
      hospital stays (P=0.008). On multivariable analysis, positive resection margins
      (P=0.046), G3 grade (P=0.036), advanced WHO classification (P=0.016), TNM stage
      (P=0.018), and readmission (P=0.019) were significantly associated with poor
      survival; however, method of resection (LDP vs. ODP) was not (P=0.254). The
      median total direct costs of LDP vs. ODP did not differ significantly.
      CONCLUSIONS: In response to the recent considerable controversy surrounding the
      costs and surgical outcomes of LDP vs. ODP, our results show that LDP for PNETs
      is cost-neutral and significantly reduces postoperative morbidity without
      compromising oncologic outcomes and survival.

PMID- 25759076
TI  - The surgical management of achalasia in the morbid obese patient.
AB  - INTRODUCTION: Morbid obesity and achalasia may coexist in the same patient. The
      surgical management of the morbidly obese patient with achalasia is complex, and
      the most effective treatment still remains controversial. The goal of our report
      is to provide our evidence-based approach for the surgical management of the
      patient with achalasia and morbid obesity. RESULTS: Three main surgical
      approaches have been used for the concomitant treatment of morbid obesity and
      achalasia: 1) a laparoscopic Heller myotomy and a laparoscopic Roux-en-Y gastric
      bypass (LRYGB); 2) a laparoscopic Heller myotomy with bilio-pancreatic diversion;
      and 3) a laparoscopic Heller myotomy with a sleeve gastrectomy. Our approach of
      choice is the first one discussed, that is the laparoscopic Heller myotomy with a
      LRYGB, as this approach can provide excellent relief of symptoms and control of
      reflux while at the same time treating obesity and its comorbidities.
      CONCLUSIONS: Achalasia and obesity can coexist, albeit infrequently. A
      laparoscopic Heller myotomy with a LRYGB allows the simultaneous treatment of
      both diseases. When a morbidly obese patient with achalasia chooses to have a
      myotomy alone and not a LRYGB, a thorough discussion of the risks and benefits
      should occur and the autonomy of the patient's decision-making should be
      respected.

PMID- 25759077
TI  - Anterior hepatic parenchymal transection for complete caudate lobectomy to treat
      liver cancer situated in or involving the paracaval portion of the caudate lobe.
AB  - BACKGROUND: Complete caudate lobectomy using the anterior hepatic parenchymal
      transection approach is a proper but technically demanding operation for tumors
      situated in or involving the paracaval portion of the caudate lobe. This study
      was intended to share our experience on this operation. METHOD: Forty-nine
      consecutive patients who received complete caudate lobectomy using the anterior
      hepatic parenchymal transection approach were studied. The clinicopathologic and
      perioperative data, complications, and survival were analyzed. RESULTS: Of the 49
      patients, 15 (30.6 %) received isolated complete caudate lobectomy and 34 (69.4
      %) received complete caudate lobectomy associated with segmentectomy IV. The
      median tumor size was 7.3 cm (2.4-18.0 cm), the operating time was 200 min (120
      370 min), and the operative blood loss was 700 ml (200-3000 ml). The
      postoperative complication rate was 36.7 %. There was no perioperative death.
      Patients in the associated complete caudate lobectomy group had larger tumors
      (P<0.001), higher platelet counts (P=0.033), shorter operation time (P=0.004),
      and less patients with residual tumor (P=0.03) than those in the isolated
      complete caudate lobectomy group. There were no significant differences in
      cirrhosis, surgical resection margin, blood loss, postoperative complications,
      and prognosis between the two groups. CONCLUSION: Complete caudate lobectomy
      using the anterior hepatic parenchymal transection approach was technically
      feasible and safe for patients with tumors situated in or involving the paracaval
      portion of the caudate lobe. Associated resection of segment IV can be used to
      facilitate the surgery and decrease the chance of local residual tumor.

PMID- 25759078
TI  - Delayed gastric emptying after pancreaticoduodenectomy. Risk factors, predictors
      of severity and outcome. A single center experience of 588 cases.
AB  - BACKGROUND: Delayed gastric emptying (DGE) is a common complication after
      pancreaticoduodenectomy (PD). This study was designed to evaluate perioperative
      risk variables for DGE after PD and analyze the factors that predict its
      severity. PATIENTS AND METHOD: Demographic data, preoperative, intraoperative,
      and postoperative variables were collected. RESULTS: A total of 588 consecutive
      patients underwent PD. One hundred and five patients (17.9 %) developed DGE of
      any type. Forty-three patients (7.3 %) had a type A, 53 patients (9.01 %) had DGE
      type B, and the remaining nine patients (1.5 %) had DGE type C. BMI > 25,
      diabetes mellitus (DM), preoperative biliary drainage, retrocolic reconstruction,
      type of pancreatic reconstruction, presence of complications, postoperative
      pancreatic fistula (POPF), and bile leaks were significantly associated with a
      higher incidence of DGE. Thirty-three (31.4 %) patients were diagnosed as primary
      DGE, while 72 (68.5 %) patients had DGE secondary to concomitant complications.
      Type B and C DGE were significantly noticed in secondary DGE (P = 0.04). Hospital
      stay was significantly shorter in primary DGE. CONCLUSION: Retrocolic GJ, DM,
      presence of complications, type of pancreatic reconstruction, and severity of
      POPF were independent significant risk factors for development of DGE. Type B and
      C DGE were significantly more in secondary DGE.

PMID- 25759079
TI  - [High-risk prostate cancer surgical margins during robot-assisted radical
      prostatectomy].
AB  - OBJECTIVE: To evaluate the feasibility of robot-assisted radical prostatectomy
      (RARP) in high risk prostate cancer (HR). The rate of positive surgical margins
      (PSM) was compared between anticipated HR cancer according to D'Amico risk
      classification and discovered postoperative HR cancer. MATERIALS AND METHODS: A
      retrospective study was conducted between 2006 and 2013 on patients who underwent
      RARP. Before surgery, patients were divided according to the D'Amico risk
      classification. After surgery, HR was defined as pT3a or pT3b, or Gleason
      score>=8 or positive lymph nodes. The rate of PSM was compared according to the
      D'Amico risk classification and postoperative HR. RESULTS: During the study, 485
      patients were reviewed. Before surgery, 10 % of cancers were classified as
      D'Amico 3 (49/485). After surgery, 27.6 % (134/485) were classified as HR. There
      was a significant difference between the rate of PSM in HR/D'Amico 3 and HR/non
      D'Amico 3 cancer, respectively 22.9 % and 34.3 % (P<0.001). CONCLUSION: The RARP
      is feasible in HR with an average of 30 % of PSM as in open surgery. However, the
      accurate assessment of preoperative HR will allow a more adapted dissection and a
      decrease of rate of PSM. So it is necessary to improve the detection of HR and so
      to select the most suitable cancer for surgery. LEVEL OF EVIDENCE: Level 5.

PMID- 25759080
TI  - Vesicocervical fistula: rare complication secondary to intrauterine device
      (Lippes loop) erosion.
AB  - We report a case of vesicocervical fistula following intrauterine device (Lippes
      loop) erosion following insertion 45 years ago. Vesicocervical fistula was
      suspected clinically. Ultrasound and magnetic resonance imaging confirmed the
      presence of a foreign body. Biopsy and magnetic resonance imaging were performed
      to rule out malignancies of the urogenital tract. The fistula was managed by
      laparotomy, hysterectomy, and bladder flap closure. We report this case because
      of its rarity.

PMID- 25759081
TI  - Can You Be Hit by Your Partner and Be Intensely in Love?
AB  - This study examines, in a multilevel context, the influence of intensity of love
      at an individual level on couples' mean reports of psychological and physical
      aggression in a sample of 2,988 adult couples of both sexes from the Region of
      Madrid. The percentages of intimate partner aggression considering the highest
      report of aggression in the couple were around 60% of psychological aggression
      and 15% of physical aggression. Multilevel models confirm that individuals who
      were less intensely in love reported a higher level of psychological aggression.
      Concerning physical aggression, men who declared they were less intensely in love
      reported a higher level of physical aggression by their partners, but this
      pattern was not found in the women. Therefore, psychological aggression plays a
      more relevant role in the intensity of love than physical aggression.

PMID- 25759082
TI  - Highly selective fluorescent and colorimetric probe for live-cell monitoring of
      sulphide based on bioorthogonal reaction.
AB  - H2S is the third endogenously generated gaseous signaling compound and has also
      been known to involve a variety of physiological processes. To better understand
      its physiological and pathological functions, efficient methods for monitoring of
      H2S are desired. Azide fluorogenic probes are popular because they can take place
      bioorthogonal reactions. In this work, by employing a fluorescein derivative as
      the fluorophore and an azide group as the recognition unit, we reported a new
      probe 5-azidofluorescein for H2S with improved sensitivity and selectivety. The
      probe shows very low background fluorescence in the absence of H2S. In the
      presence of H2S, however, a significant enhancement for excited fluorescence were
      observed, resulting in a high sensitivity to H2S in buffered (10 mmol/L HEPES, pH
      7.0) aqueous acetonitrile solution (H2O/CH3CN = 1:3, v/v) with a detection limit
      of 0.035 MUmol/L observed, much lower than the previously reported probes. All
      these features are favorable for direct monitoring of H2S with satisfactory
      sensitivity, demonstrating its value of practical application.

PMID- 25759084
TI  - Does thermal treatment merely make a H2O-saturated Nafion membrane lose its
      absorbed water at high temperature?
AB  - Investigating the dehydration process of a Nafion membrane helps to understand
      the mechanism of the decrease in its proton conductivity under high-temperature
      and low-humidity conditions. Herein, the influence of thermal treatment on a H2O
      saturated Nafion membrane was in situ studied by FTIR spectroscopy. With the aid
      of generalized two-dimensional correlation spectroscopy (2Dcos), the
      microstructural changes during the thermal treatment were discussed in detail. In
      short, side-chain regions first lost H2O, followed by the H2O loss in ionic
      cluster domains. It resulted in shrunken ionic channels in the Nafion membrane,
      which exhibited a negative influence on its proton conduction. The immediate
      aftermath was the crystallization of amorphous backbone regions. All these
      results were confirmed by TGA and XRD techniques, and the 2Dcos method was first
      applied in TGA and XRD results in this field. 

PMID- 25759083
TI  - Two-year survival of patients screened for transcatheter aortic valve replacement
      with potentially malignant incidental findings in initial body computed
      tomography.
AB  - AIMS: Recently, transcatheter aortic valve replacement (TAVR) has evolved as the
      standard treatment in patients with inoperable aortic valve stenosis. According
      to TAVR guidelines, body computed tomography (CT) is recommended for pre
      procedural planning. Due to the advanced age of these patients, multiple
      radiological potentially malignant incidental findings (pmIFs) appear in this
      cohort. It is unknown how pmIFs influence the decision by the heart team to
      intervene and the mortality. METHODS AND RESULTS: We evaluated in a retrospective
      single-centre observational study 414 participants screened for TAVR with dual
      source CT between October 2010 and December 2012. pmIFs are common and appeared
      in 18.7% of all patients screened for TAVR. The decision to intervene by TAVR or
      surgical aortic valve replacement (SAVR) was made by an interdisciplinary heart
      team and the role of pmIF in decision-making and time to treatment with TAVR or
      SAVR was analysed, retrospectively. The appearance of a pmIF vs. no pmIF did not
      significantly influence therapeutic decisions [odds ratio (OR) 1.14; P = 0.835]
      or time to treatment (91 +/- 152 vs. 61 +/- 109 days, respectively). Several
      findings, which are highly suspicious for malignancy, were less likely associated
      with invasive treatment (OR 0.207; P = 0.046). Patient survival was evaluated for
      at least 2 years until January 2014. Two-year survival of patients after TAVR or
      SAVR, treated according to the heart team decision, was ~75% and independent from
      the presence of a non-severe (P = 0.923) or severe (P = 0.823) pmIF. CONCLUSION:
      The study indicates that frequently occurring radiologic pmIF did not influence 2
      year survival after a decision to intervene was made by an interdisciplinary
      heart team.

PMID- 25759086
TI  - Abstracts of the 6th Annual Scientific Meeting of the British Obesity & Metabolic
      Surgery Society (BOMSS), 22-23 January 2015, Newcastle, UK.

PMID- 25759085
TI  - Three-dimensional architecture of podocytes revealed by block-face scanning
      electron microscopy.
AB  - Block-face imaging is a scanning electron microscopic technique which enables
      easier acquisition of serial ultrastructural images directly from the surface of
      resin-embedded biological samples with a similar quality to transmission electron
      micrographs. In the present study, we analyzed the three-dimensional architecture
      of podocytes using serial block-face imaging. It was previously believed that
      podocytes are divided into three kinds of subcellular compartment: cell body,
      primary process, and foot process, which are simply aligned in this order. When
      the reconstructed podocytes were viewed from their basal side, the foot processes
      were branched from a ridge-like prominence, which was formed on the basal surface
      of the primary process and was similar to the usual foot processes in structure.
      Moreover, from the cell body, the foot processes were also emerged via the ridge
      like prominence, as found in the primary process. The ridge-like prominence
      anchored the cell body and primary process to the glomerular basement membrane,
      and connected the foot processes to the cell body and primary process. In
      conclusion, serial block-face imaging is a powerful tool for clear understanding
      the three-dimensional architecture of podocytes through its ability to reveal
      novel structures which were difficult to determine by conventional transmission
      and scanning electron microscopes alone. 

PMID- 25759087
TI  - Total synthesis of clostrubin.
AB  - Clostrubin is a potent antibiotic against methicillin- and vancomycin-resistant
      bacteria that was isolated from a strictly anaerobic bacterium Clostridium
      beijerinckii in 2014. This polyphenol possesses a fully substituted arene moiety
      on its pentacyclic scaffold, which poses a considerable challenge for chemical
      synthesis. Here we report the first total synthesis of clostrubin in nine steps
      (the longest linear sequence). A desymmetrization strategy is exploited based on
      the inherent structural feature of the natural product. Barton-Kellogg
      olefination forges the two segments together to form a tetrasubstituted alkene. A
      photo-induced 6pi electrocyclization followed by spontaneous aromatization
      constructs the hexasubstituted B ring at a late stage. In total, 200 mg of
      clostrubin are delivered through this approach. 

PMID- 25759088
TI  - Left atrial function in volume versus pressure overloaded left atrium.
AB  - Left atrial (LA) pressure and volume overload both result in cavity enlargement
      and complications. LA volume has been shown to predict such complications, but it
      does not reflect myocardial function, which can be accurately assessed using
      myocardial deformation measurements. We hypothesized that volume overloaded LA
      have maintained myocardial function compared to pressure overloaded ones. We
      tested this hypothesis in 44 patient (mean age 62 +/- 12 years) with LA volume
      overload (LAVOL) due to severe mitral regurgitation (MR) with no indirect signs
      of elevated left ventricular (LV) filling pressures based on Doppler measured
      isovolumic relaxation time >60 ms. We compared them with 24 (mean age 64 +/- 12
      years) patient with LA pressure overload (LAPOL) who proved to have PCWP >15 mmHg
      on right heart catheterization. Twenty-seven healthy controls (mean age 57 +/- 10
      years) constituted a control group. Patients with LAVOL had larger LA volumes,
      higher LV ejection fraction, global LV strain (LVGLS) and transmitral and
      pulmonary veins flow velocities (p < 0.05) and better LA atrial strain rate
      (LASR) function compared to LAPOL (p < 0.001). In LAVOL, the LASR during atrial
      contraction (LASRa) was lower than in controls (p < 0.05) indicating LA
      mechanical disturbances. LVGLS correlated with peak atrial longitudinal systolic
      strain in the whole group (r = -0.65, p < 0.001) and less so with LASRa (r = 
      0.43, p < 0.001) CONCLUSION: Irrespective of a smaller LA volume, LAVOL had less
      negative effect on LA myocardial function than LAPOL. Thus, monitoring atrial
      myocardial contraction might be useful in following patients with significant MR.

PMID- 25759089
TI  - Tobacco smoking and cannabis use in a longitudinal birth cohort: evidence of
      reciprocal causal relationships.
AB  - BACKGROUND: There is evidence of associations between tobacco and cannabis use
      that are consistent with both a classical stepping-stone scenario that posits the
      transition from tobacco use to cannabis use ('gateway' effect of tobacco) and
      with the reverse process leading from cannabis use to tobacco abuse ('reverse
      gateway' effect of cannabis). The evidence of direct causal relationships between
      the two disorders is still missing. METHODS: We analysed data from the
      Christchurch Health and Development Study (CHDS) longitudinal birth cohort using
      advanced statistical modelling to control for fixed sources of confounding and to
      explore causal pathways. The data were analysed using both: (a) conditional fixed
      effects logistic regression modelling; and (b) a systematic structural equation
      modelling approach previously developed to investigate psychiatric co-morbidities
      in the same cohort. RESULTS: We found significant (p<0.05) associations between
      the extent of cannabis use and tobacco smoking and vice versa, after controlling
      for non-observed fixed confounding factors and for a number of time-dynamic
      covariate factors (major depression, alcohol use disorder, anxiety disorder,
      stressful life events, deviant peer affiliations). Furthermore, increasing levels
      of tobacco smoking were associated with increasing cannabis use (p=0.02) and vice
      versa (p<0.001) over time. CONCLUSIONS: Our results lend support to the notion of
      both of 'gateway' and 'reverse gateway' effects. That is, the association between
      tobacco and cannabis use arises from a reciprocal feedback loop involving
      simultaneous causation between tobacco use disorder and cannabis use disorder.

PMID- 25759090
TI  - Contradictory roles of Porphyromonas gingivalis gingipains in caspase-1
      activation.
AB  - Porphyromonas gingivalis utilizes its major proteases, Arg gingipains (RgpA and
      RgpB) and Lys gingipain (Kgp), for dysregulation of host immune systems. The aim
      of this study was to investigate the roles of gingipains in caspase-1 activation
      and its sequelae in P. gingivalis-infected macrophages. Infection with P.
      gingivalis at low multiplicity of infections (MOIs), but not at high MOIs,
      resulted in low levels of interleukin-1beta and lactate dehydrogenase without
      detectable active caspase-1 in the culture supernatants. The proteins released
      from caspase-1-activated cells were rapidly degraded by gingipains. However, P.
      gingivalis with gingipains induced higher intracellular caspase-1 activity in the
      infected cells than the gingipain-null mutant, which was associated with ATP
      release from the infected cells. In addition, growing the gingipain-null mutant
      with gingipains enhanced caspase-1 activation by the mutant. In contrast,
      inhibition of the protease activity of Kgp or Rgps increased the caspase-1
      activating potential of wild-type P. gingivalis, indicating an inhibitory effect
      of the collaborative action of Kgp and Rgps. These results illuminate the
      contradictory roles of gingipains in the manipulation of host defence systems by
      P. gingivalis, as they act by both stimulating and inhibiting innate immune
      responses. 

PMID- 25759091
TI  - Diffuse intrapulmonary malignant mesothelioma presenting with miliary pulmonary
      nodules: A case report.
AB  - A 67-year-old male with a history of asbestos exposure presented with fever,
      cough, and dyspnea and was found to have diffuse granular shadowing in both
      lungs, right pleural effusion, and hilar and mediastinal lymphadenopathy upon
      chest computed tomography. For definitive diagnosis, a thoracoscopic lung biopsy
      was performed. Intraoperative findings showed no remarkable macroscopic changes
      in the visceral and parietal pleura, although a high level of hyaluronic acid in
      the pleural effusion was noted. Histological findings showed proliferation of
      atypical cells with round-to-oval nuclei, prominent nucleoli, and eosinophilic
      cytoplasms. These cells were arranged into sheets or tubules and were located
      predominantly in the lung parenchyma. Lymphovascular invasion was conspicuous.
      Immunohistochemically, tumor cells were positive for calretinin, D2-40, and
      CK5/6, focally positive for Ber-EP4, but negative for WT-1, TTF-1, CEA, and
      MOC31. Fluorescence in situ hybridization for the tumor suppressor p16 revealed
      homozygous deletion in the tumor cells. Therefore, we diagnosed the tumor as
      diffuse intrapulmonary malignant mesothelioma (DIMM). The patient had a poor
      response to chemotherapy and died 1 year after diagnosis. Although rare, DIMM
      should be considered when patients present with multiple, tiny intrapulmonary
      nodules, regardless of macroscopic pleural changes. Furthermore, this is the
      first report on p16 status in DIMM. 

PMID- 25759092
TI  - Highly crystalline MOF-based materials grown on electrospun nanofibers.
AB  - Supported Metal Organic Frameworks (MOFs) with a high specific surface area are
      of great interest for applications in gas storage, separation, sensing, and
      catalysis. In the present work we report the synthesis of a novel composite
      architecture of MOF materials supported on a flexible mat of electrospun
      nanofibers. The system, based on three-dimensional interwoven nanofibers, was
      designed by using a low-cost and scalable multistep synthesis protocol involving
      a combination of electrospinning and low-temperature atomic layer deposition of
      oxide materials, and their subsequent solvothermal conversion under either
      conventional or microwave-assisted heating. This highly versatile approach allows
      the production of different types of supported MOF crystals with controlled
      sizes, morphology, orientation and high accessibility. 

PMID- 25759093
TI  - Inhomogeneous relaxation dynamics and phase behaviour of a liquid crystal
      confined in a nanoporous solid.
AB  - We report filling-fraction dependent dielectric spectroscopy measurements on the
      relaxation dynamics of the rod-like nematogen 7CB condensed in 13 nm silica
      nanochannels. In the film-condensed regime, a slow interface relaxation dominates
      the dielectric spectra, whereas from the capillary-condensed state up to complete
      filling an additional, fast relaxation in the core of the channels is found. The
      temperature-dependence of the static capacitance, representative of the averaged,
      collective molecular orientational ordering, indicates a continuous, paranematic
      to-nematic (P-N) transition, in contrast to the discontinuous bulk behaviour. It
      is well described by a Landau-de-Gennes free energy model for a phase transition
      in cylindrical confinement. The large tensile pressure of 10 MPa in the capillary
      condensed state, resulting from the Young-Laplace pressure at highly curved
      liquid menisci, quantitatively accounts for a downward-shift of the P-N
      transition and an increased molecular mobility in comparison to the unstretched
      liquid state of the complete filling. The strengths of the slow and fast
      relaxations provide local information on the orientational order: the
      thermotropic behaviour in the core region is bulk-like, i.e. it is characterized
      by an abrupt onset of the nematic order at the P-N transition. By contrast, the
      interface ordering exhibits a continuous evolution at the P-N transition. Thus,
      the phase behaviour of the entirely filled liquid crystal-silica nanocomposite
      can be quantitatively described by a linear superposition of these distinct
      nematic order contributions. 

PMID- 25759094
TI  - A Qualitative Study of Potential Suicide Risk Factors Among Operation Iraqi
      Freedom/Operation Enduring Freedom Soldiers Returning to the Continental United
      States (CONUS).
AB  - OBJECTIVE: A qualitative study among Operation Enduring Freedom/Operation Iraqi
      Freedom (OEF/OIF) Soldiers was conducted to explore potential constructs
      underlying suicide according to the interpersonal-psychological theory of suicide
      (IPTS); these include burdensomeness, failed belonging, and acquired capability.
      METHODS: Qualitative semistructured interviews were conducted with 68 Soldiers at
      3 months post-OEF/OIF deployment. Soldiers were asked about changes in their
      experiences of pain, burdensomeness, and lack of belonging. The methodology
      employed was descriptive phenomenological. RESULTS: Transcripts were reviewed and
      themes related to the IPTS constructs emerged. Soldiers' postdeployment
      transition experiences included higher pain tolerance, chronic pain, emotional
      reactivity, emotional numbing and distancing, changes in physical functioning,
      combat guilt, discomfort with care seeking, and difficulties reintegrating into
      family and society. CONCLUSIONS: Findings highlight the utility of the IPTS in
      understanding precursors to suicide associated with transition from deployment,
      as well as treatment strategies that may reduce risk in Soldiers during
      reintegration.

PMID- 25759095
TI  - High-flow nasal cannulae are associated with increased diaphragm activation
      compared with nasal continuous positive airway pressure in preterm infants.
AB  - AIM: High-flow nasal cannulae (HFNC) are increasingly used for respiratory
      management of preterm infants. However, their ability to provide support compared
      to nasal continuous positive airway pressure (CPAP) has been questioned. We
      compared the effect of HFNC versus nasal CPAP on diaphragm electrical activity
      (EAdi) in preterm infants. METHODS: Preterm infants <=1500 g were randomised in a
      crossover design to receive 2 hours of either Infant Flow((r)) CPAP (IF-CPAP) at
      5-6 cmH2 O or HFNC with the flow rate adjusted to achieve an equivalent
      pharyngeal pressure. A feeding catheter with miniaturised sensors was inserted
      for continuous EAdi measurement. RESULTS: The study comprised ten infants.
      Physiologic parameters and oxygen requirements were not different between the two
      modes. However, seven infants demonstrated a higher EAdi peak and six showed a
      higher EAdi tonic on HFNC, even though the mean group data showed no difference
      between HFNC and IF-CPAP. Neural inspiratory time was significantly longer with
      HFNC than IF-CPAP (0.55 +/- 0.11 versus 0.48 +/- 0.06 seconds, p = 0.018).
      CONCLUSION: In this cohort of preterm infants, the majority exhibited greater
      diaphragm activation, as assessed by neural breathing patterns, when supported
      with HFNC than IF-CPAP, suggesting that nasal CPAP may provide more effective
      respiratory support.

PMID- 25759097
TI  - PRRSV structure, replication and recombination: Origin of phenotype and genotype
      diversity.
AB  - Porcine reproductive and respiratory disease virus (PRRSV) has the intrinsic
      ability to adapt and evolve. After 25 years of study, this persistent pathogen
      has continued to frustrate efforts to eliminate infection of herds through
      vaccination or other elimination strategies. The purpose of this review is to
      summarize the research on the virion structure, replication and recombination
      properties of PRRSV that have led to the extraordinary phenotype and genotype
      diversity that exists worldwide. 

PMID- 25759096
TI  - Bacterial CRISPR/Cas DNA endonucleases: A revolutionary technology that could
      dramatically impact viral research and treatment.
AB  - CRISPR/Cas systems mediate bacterial adaptive immune responses that evolved to
      protect bacteria from bacteriophage and other horizontally transmitted genetic
      elements. Several CRISPR/Cas systems exist but the simplest variant, referred to
      as Type II, has a single effector DNA endonuclease, called Cas9, which is guided
      to its viral DNA target by two small RNAs, the crRNA and the tracrRNA. Initial
      efforts to adapt the CRISPR/Cas system for DNA editing in mammalian cells, which
      focused on the Cas9 protein from Streptococcus pyogenes (Spy), demonstrated that
      Spy Cas9 can be directed to DNA targets in mammalian cells by tracrRNA:crRNA
      fusion transcripts called single guide RNAs (sgRNA). Upon binding, Cas9 induces
      DNA cleavage leading to mutagenesis as a result of error prone non-homologous end
      joining (NHEJ). Recently, the Spy Cas9 system has been adapted for high
      throughput screening of genes in human cells for their relevance to a particular
      phenotype and, more generally, for the targeted inactivation of specific genes,
      in cell lines and in vivo in a number of model organisms. The latter aim seems
      likely to be greatly enhanced by the recent development of Cas9 proteins from
      bacterial species such as Neisseria meningitidis and Staphyloccus aureus that are
      small enough to be expressed using adeno-associated (AAV)-based vectors that can
      be readily prepared at very high titers. The evolving Cas9-based DNA editing
      systems therefore appear likely to not only impact virology by allowing
      researchers to screen for human genes that affect the replication of pathogenic
      human viruses of all types but also to derive clonal human cell lines that lack
      individual gene products that either facilitate or restrict viral replication.
      Moreover, high titer AAV-based vectors offer the possibility of directly
      targeting DNA viruses that infect discrete sites in the human body, such as
      herpes simplex virus and hepatitis B virus, with the hope that the entire
      population of viral DNA genomes might be destroyed. In conclusion, we believe
      that the continued rapid evolution of CRISPR/Cas technology will soon have a
      major, possibly revolutionary, impact on the field of virology. 

PMID- 25759098
TI  - Cis-acting RNA elements in positive-strand RNA plant virus genomes.
AB  - Positive-strand RNA viruses are the most common type of plant virus. Many aspects
      of the reproductive cycle of this group of viruses have been studied over the
      years and this has led to the accumulation of a significant amount of insightful
      information. In particular, the identification and characterization of cis-acting
      RNA elements within these viral genomes have revealed important roles in many
      fundamental viral processes such as virus disassembly, translation, genome
      replication, subgenomic mRNA transcription, and packaging. These functional cis
      acting RNA elements include primary sequences, secondary and tertiary structures,
      as well as long-range RNA-RNA interactions, and they typically function by
      interacting with viral or host proteins. This review provides a general overview
      and update on some of the many roles played by cis-acting RNA elements in
      positive-strand RNA plant viruses. 

PMID- 25759101
TI  - Coronary embolization in hypertrophic cardiomyopathy with left ventricular apical
      aneurysm.
AB  - Patients with left ventricular apical aneurysms represent a unique patient
      subgroup in the broad clinical spectrum of hypertrophic cardiomyopathy (HC)
      associated with the risk for sudden death, heart failure, and peripheral
      thromboembolism. Routine chronic anticoagulation has not been a standard
      recommendation for these patients. We present a 36-year-old patient with HC with
      features of acute coronary syndrome, likely secondary to coronary thromboembolism
      as a complication of left ventricular apical aneurysm. Our experience with this
      patient raises consideration for prophylactic anticoagulant therapy for this
      unusual subset of patients with HC. 

PMID- 25759100
TI  - Nonuse of dental service by schoolchildren in Southern Brazil: impact of
      socioeconomics, behavioral and clinical factors.
AB  - OBJECTIVES: To assess clinical, behavioral and socioeconomic factors associated
      with nonuse of dental services by schoolchildren. METHODS: A cross-sectional
      school-based study with 1211 children aged 8-12 years was carried out in Pelotas,
      Brazil. The outcome (never having had a dental appointment) and independent
      variables were collected through interview with parents and children, including
      sex, age, parent's schooling, family income, self-perception about oral health,
      and dental fear. Dental caries was assessed by clinical examination performed at
      schools. RESULTS: 291 (24.3 %; 95 % CI 22.0-26.9) of the children had never
      visited a dentist. Multivariate Poisson regression analysis showed that the
      outcome was associated with children from mothers with little education
      (<=0.001), from public schools (<=0.001), from crowded households (<=0.001), who
      had no caries (<=0.001), who had dental fear (<=0.001), and who started oral
      hygiene later (0.04). CONCLUSIONS: Despite the extensive increase in oral health
      coverage, especially in the public system in the last years in Brazil, there is
      still an unassisted portion of the population of schoolchildren. It was observed
      that socioeconomic, behavioral, and clinical factors influenced the nonuse of
      dental services.

PMID- 25759103
TI  - Meta-analysis of trials on mortality after percutaneous coronary intervention
      compared with medical therapy in patients with stable coronary heart disease and
      objective evidence of myocardial ischemia.
AB  - Outcomes of percutaneous coronary intervention (PCI) versus medical therapy (MT)
      in the management of stable ischemic heart disease (SIHD) remain controversial,
      with some but not all studies showing improved results in patients with ischemia.
      We sought to elucidate whether PCI improves mortality compared to MT in patients
      with objective evidence of ischemia (assessed using noninvasive imaging or its
      invasive equivalent). We performed a systematic review and meta-analysis of
      randomized controlled trials (RCTs) comparing PCI to MT in patients with SIHD. To
      maintain a high degree of specificity for ischemia, studies were only included if
      ischemia was defined on the basis of noninvasive stress imaging or abnormal
      fractional flow reserve. The primary outcome was all-cause mortality. We
      identified 3 RCTs (Effects of Percutaneous Coronary Interventions in Silent
      Ischemia After Myocardial Infarction II, Fractional Flow Reserve versus
      Angiography for Multivessel Evaluation 2, and a substudy of the Clinical Outcomes
      Utilizing Revascularization and Aggressive Drug Evaluation trial) enrolling a
      total of 1,557 patients followed for an average of 3.0 years. When compared with
      MT in this population of patients with objective ischemia, PCI was associated
      with lower mortality (hazard ratio 0.52, 95% confidence interval 0.30 to 0.92,
      p=0.02). There was no evidence of study heterogeneity or bias among included
      trials. In this meta-analysis of published RCTs, PCI was shown to have a
      mortality benefit over MT in patients with SIHD and objective assessment of
      ischemia using noninvasive imaging or its invasive equivalent. In conclusion,
      this study provides insight into the management of a higher-risk SIHD population
      that is the focus of the ongoing International Study of Comparative Health
      Effectiveness with Medical and Invasive Approaches trial.

PMID- 25759102
TI  - Relation of fish oil supplementation to markers of atherothrombotic risk in
      patients with cardiovascular disease not receiving lipid-lowering therapy.
AB  - Fish oil supplementation (FOS) is known to have cardiovascular benefits. However,
      the effects of FOS on thrombosis are incompletely understood. We sought to
      determine if the use of FOS is associated with lower indices of atherothrombotic
      risk in patients with suspected coronary artery disease (sCAD). This is a
      subgroup analysis of consecutive patients with sCAD (n=600) enrolled in the Multi
      Analyte, Thrombogenic, and Genetic Markers of Atherosclerosis study. Patients on
      FOS were compared with patients not on FOS. Lipid profile was determined by
      vertical density gradient ultracentrifugation (n=520), eicosapentaenoic
      acid+docosahexaenoic acid was measured by gas chromatography (n=437), and AtherOx
      testing was performed by immunoassay (n=343). Thromboelastography (n=419), ADP-
      and collagen-induced platelet aggregation (n=137), and urinary 11
      dehydrothromboxane B2 levels (n=259) were performed immediately before elective
      coronary angiography. In the total population, FOS was associated with higher
      eicosapentaenoic acid+docosahexaenoic acid content (p<0.001), lower triglycerides
      (p=0.04), total very low-density lipoprotein cholesterol (p=0.002), intermediate
      density lipoprotein cholesterol (p=0.02), and AtherOx levels (p=0.02) but not in
      patients on lipid-lowering therapy. Patients not on lipid-lowering therapy taking
      FOS had lower very low-density lipoprotein cholesterol, intermediate-density
      lipoprotein cholesterol, remnant lipoproteins, triglycerides, low-density
      lipoprotein cholesterol, AtherOx levels, collagen-induced platelet aggregation,
      thrombin-induced platelet-fibrin clot strength, and shear elasticity (p<0.03 for
      all). In clopidogrel-treated patients, there was no difference in ADP-induced
      aggregation between FOS groups. Patients on FOS had lower urinary 11
      dehydrothromboxane B2 levels regardless of lipid-lowering therapy (p<0.04). In
      conclusion, the findings of this study support the potential benefit of FOS for
      atherothrombotic risk reduction in sCAD with the greatest benefit in patients not
      receiving lipid-lowering therapy. Future prospective studies to compare FOS with
      lipid-lowering therapy and to assess the independent effects of FOS on
      thrombogenicity are needed.

PMID- 25759104
TI  - Predictors of high on-aspirin platelet reactivity in high-risk vascular patients
      treated with single or dual antiplatelet therapy.
AB  - Aspirin is the key treatment in the secondary prevention of atherothrombosis.
      Interindividual variability of response has been linked to a higher risk for
      ischemic events. The aim of this study was to identify clinical and biologic
      factors predicting high on-aspirin platelet reactivity (HPR) in a high-risk,
      "real-world" population of vascular patients. All platelet testing performed from
      2011 to 2013 in consecutive patients receiving long-term treatment with aspirin
      for coronary or cerebrovascular disease was retrospectively analyzed. Indications
      for platelet testing were recurrent ischemic events or high-risk angioplasty. HPR
      was defined as aggregation intensity>=20% using light-transmission aggregometry
      with arachidonic acid 0.5 mg/ml. Collagen-epinephrine platelet function analysis
      was also performed (threshold<165 seconds). Cardiovascular risk factors, usual
      biologic parameters, and antiplatelet treatment were recorded. A total of 1,508
      patients were included (mean age 63 years, 71% men, 23% with diabetes).
      Antiplatelet treatment was aspirin alone in 333 patients and dual-antiplatelet
      therapy in 1,175 patients. HPR was found in 11.1% of patients. In multivariate
      analysis, independent predictive factors of HPR on light-transmission
      aggregometry with arachidonic acid were diabetes mellitus (odds ratio [OR] 2.10,
      95% confidence interval [CI] 1.39 to 3.16), age (OR 1.25, 95% CI 1.06 to 1.47),
      fibrinogen level (OR 1.20, 95% CI 1.02 to 1.42), and von Willebrand factor level
      (OR 1.06, 95% CI 1.03 to 1.09). On light-transmission aggregometry with
      arachidonic acid and collagen-epinephrine platelet function analysis, fibrinogen
      remained the main factor associated with HPR (OR 1.33, 95% CI 1.19 to 1.61).
      Similar results were found in patients treated with aspirin alone or dual
      antiplatelet therapy. A fibrinogen level>4.0 g/L was associated with a 3.9-fold
      increased risk for HPR in patients aged <75 years. In conclusion, fibrinogen
      level was the major predictor of HPR on aspirin in this large population of high
      risk vascular patients.

PMID- 25759099
TI  - Molecular biology of hepatitis B virus infection.
AB  - Human hepatitis B virus (HBV) is the prototype of a family of small DNA viruses
      that productively infect hepatocytes, the major cell of the liver, and replicate
      by reverse transcription of a terminally redundant viral RNA, the pregenome. Upon
      infection, the circular, partially double-stranded virion DNA is converted in the
      nucleus to a covalently closed circular DNA (cccDNA) that assembles into a
      minichromosome, the template for viral mRNA synthesis. Infection of hepatocytes
      is non-cytopathic. Infection of the liver may be either transient (<6 months) or
      chronic and lifelong, depending on the ability of the host immune response to
      clear the infection. Chronic infections can cause immune-mediated liver damage
      progressing to cirrhosis and hepatocellular carcinoma (HCC). The mechanisms of
      carcinogenesis are unclear. Antiviral therapies with nucleoside analog inhibitors
      of viral DNA synthesis delay sequelae, but cannot cure HBV infections due to the
      persistence of cccDNA in hepatocytes. 

PMID- 25759105
TI  - Impact of pre-procedural serum albumin levels on outcome of patients undergoing
      transcatheter aortic valve replacement.
AB  - Risk assessment for transcatheter aortic valve replacement (TAVR) patients is
      challenging, and surgical scores do not optimally correlate with outcome. The aim
      of this study was to assess the correlation between serum albumin and survival of
      patients with symptomatic severe aortic stenosis undergoing TAVR. Patients with
      severe aortic stenosis who underwent TAVR were categorized into 2 groups
      according to low and normal preprocedural serum albumin (<3.5 and >=3.5 g/dl,
      respectively). The all-cause mortality rates at hospital discharge, at 30-day and
      1-year follow-up were compared across the groups. Additionally, a Cox
      proportional-hazards model was generated to assess the independent effect of
      serum albumin at 1-year follow-up. Among 567 consecutive patients who underwent
      TAVR, 476 (84%) had documented preprocedural serum albumin measurements. Of
      these, 50% had low serum albumin levels, and 50% had normal serum albumin levels.
      Baseline and procedural characteristics, including age, gender, and transapical
      access, were similar among the groups. Prevalence of left ventricular ejection
      fraction<40% was higher in patients with low albumin (29% vs 20%, p=0.02), and
      risk assessment according to Society of Thoracic Surgeons score tended to be
      higher in the low-albumin group (10+/-4.7 vs 9.4+/-4.4, p=0.09). Patients
      presenting with low albumin had higher in-hospital mortality (11% vs 5%), as well
      as at 30-day (12% vs 6%, p=0.01) and 1-year (29% vs 19%, p=0.02) follow-up. Serum
      albumin was independently associated with 1-year mortality (adjusted hazard ratio
      per 0.1 g/dl decrease 1.64, 95% confidence interval 2.50 to 1.75, p=0.02), along
      with body mass index<20 kg/m2 (hazard ratio 1.89, 95% confidence interval 3.33 to
      1.75, p=0.03). In conclusion, preprocedural serum albumin level and low body mass
      index are independently associated with mortality in patients who undergo TAVR.
      Patients with severe aortic stenosis and low albumin levels should undergo
      careful evaluation before and after TAVR.

PMID- 25759106
TI  - Role of hydration in contrast-induced nephropathy in patients who underwent
      primary percutaneous coronary intervention.
AB  - To investigate the role of hydration to prevent contrast-induced nephropathy
      (CIN) in patients with ST-segment elevation myocardial infarction (STEMI) who
      underwent primary percutaneous coronary intervention (PPCI), we prospectively
      included 408 consecutive patients who were randomly assigned to receive either
      hydration with isotonic saline (1 ml/kg/h since the beginning of the procedure
      and for 24 hours after it: NS+ group) or not (NS- group). All patients received
      an iso-osmolar nonionic contrast medium. The primary end point was the
      development of CIN: >=25% or >=0.5 mg/dl increase in serum creatinine within 3
      days after the procedure. CIN was observed in 14% of patients: 21% in the NS-
      group and 11% in the NS+ group (p=0.016). CIN was significantly associated with
      death (15.2% vs 2.8%; p<0.0001) and need for dialysis (13.4% vs 0%; p<0.0001). In
      multivariate analysis, the only predictors of CIN were hydration (OR=0.29 [0.14
      to 0.66]; p=0.003) and the hemoglobin before the procedure (OR=0.69 [0.59 to
      0.88]; p<0.0001). In conclusion, intravenous saline hydration during PPCI reduced
      the risk of CIN to 48%. Patients with CIN had increased mortality and need for
      dialysis. Given the higher incidence of CIN in emergent procedures, and its
      morbidity and mortality, preventive hydration should be mandatory in them unless
      contraindicated.

PMID- 25759107
TI  - Psychological distress as a mediator of the association between disease severity
      and occupational functioning among employed spouses of women recently diagnosed
      with breast cancer.
AB  - OBJECTIVE: The purpose was to evaluate whether patient and spouse cancer-specific
      distress mediated the association between cancer severity and occupational
      functioning among employed spouses of women diagnosed with breast cancer. We
      examined whether sociodemographic characteristics, lower spouse-reported marital
      quality, and lower spouse self-rated health were associated with poorer spouse
      occupational functioning. METHODS: One hundred forty-three currently employed
      spouses of women diagnosed with breast cancer were administered measures of
      socioeconomic status, occupational functioning (work absenteeism, low
      productivity, and poor performance), cancer-specific distress, marital quality,
      and self-rated health. Patients completed measures of cancer-related distress and
      functional impairment and cancer stage were collected from medical charts.
      RESULTS: In the model evaluating work absenteeism, greater patient functional
      impairment was associated with more absenteeism, but there was no evidence of a
      mediating effect for either partners' cancer-specific distress. Higher cancer
      stage and more functional impairment were associated with higher spouse cancer
      specific distress, which in turn predicted poorer work productivity. Patient
      cancer-specific distress did not mediate the association between patient
      functional impairment or cancer stage and spouse work productivity. Finally,
      higher cancer stage was associated with more spouse cancer-specific distress,
      which in turn predicted poorer work performance. There were no direct or indirect
      effects of the patient's functional impairment on spouse work performance.
      CONCLUSIONS: Distressed spouses are more likely to have poorer work productivity
      after their partners' breast cancer diagnosis. These spouses may need assistance
      in managing their distress and the patient's functional impairment to ensure that
      their work productivity is not adversely affected.

PMID- 25759108
TI  - Fibrillar networks of glycyrrhizic acid for hybrid nanomaterials with catalytic
      features.
AB  - Self-assembly of the naturally occurring sweetening agent, glycyrrhizic acid (GA)
      in water is studied by small-angle X-ray scattering and microscopic techniques.
      Statistical analysis on atomic force microscopy images reveals the formation of
      ultralong GA fibrils with uniform thickness of 2.5 nm and right-handed twist with
      a pitch of 9 nm, independently of GA concentration. Transparent nematic GA
      hydrogels are exploited to create functional hybrid materials. Two-fold and three
      fold hybrids are developed by introducing graphene oxide (GO) and in situ
      synthesized gold nanoparticles (Au NPs) in the hydrogel matrix for catalysis
      applications. In the presence of GO, the catalytic efficiency of Au NPs in the
      reduction of p-nitrophenol to p-aminophenol is enhanced by 2.5 times. Gold
      microplate single crystals are further synthesized in the GA hydrogel, expanding
      the scope of these hybrids and demonstrating their versatility in materials
      design. 

PMID- 25759109
TI  - [Rest gated-SPECT myocardial perfusion post (99m)Tc-MIBI injection in a patient
      with acute chest pain and with no medical history of ischemic heart disease].
AB  - Gated-SPECT myocardial perfusion imaging is a widely used technique indicated for
      assessment of patients with no clear diagnosis of ischemic heart disease. Early
      rest gated-SPECT myocardial perfusion study in patients with acute chest pain has
      high sensitivity and high negative predictive value for ruling out coronary
      disease. We report a case of a patient admitted for the study of her chest pain.
      She underwent a myocardial perfusion stress-rest whose interpretation could have
      been equivocal due to the clinical status of the patient during the injection of
      the radiotracer. 

PMID- 25759110
TI  - From benzalkonium chloride-preserved Latanoprost to Polyquad-preserved
      Travoprost: a 6-month study on ocular surface safety and tolerability.
AB  - BACKGROUND: To evaluate the safety and tolerability of Polyquad-preserved
      Travoprost (PQ-Travoprost) in patients previously treated with benzalkonium
      chloride (BAK)-preserved Latanoprost. METHODS: Cohort 6-month study on open-angle
      glaucoma or ocular hypertension patients. Complete ophthalmic examination,
      intraocular pressure (IOP) measurement and ocular surface status (tear film break
      up time [TF-BUT], corneal staining and ocular surface disease index [OSDI]) were
      evaluated at baseline and 6 months later. RESULTS: A total of 44 patients were
      enrolled. Median (interquartile range [IQR]) baseline IOP was 18 (15.5 - 21) and
      16 (14 - 17) mmHg (p < 0.0001) after 6 months. At baseline, 18 (40.9%) patients
      presented an IOP of < 18 mmHg, 11 (25%) < 16 mmHg, 2 (4.3%) < 14 mmHg and 1
      (2.3%) < 12 mmHg; 6 months later the proportions were 36 (81.8%) (p < 0.0001), 21
      (47.7%) (p = 0.00075), 8 (18.2%) (p = 0.0143) and 6 (13.6%) (p = 0.0253).
      Concerning safety, TF-BUT improved from 8 [IQR 6 - 10] to 10 [IQR 8 - 12] s (p <
      0.0001). No eye developed corneal staining; punctate keratitis was absent in 13
      (29.5%) patients at baseline and in 31 (70.4%) after 6 months (p < 0.001). OSDI
      changed from 16 (10 - 30) to 9 (2 - 20). CONCLUSIONS: No patient treated with PQ
      Travoprost developed ocular surface disease after 6 months of monotherapy,
      whereas many patients reached a good IOP control with lower IOP values. Ocular
      surface status statistically improved when examined by TF-BUT and corneal
      staining.

PMID- 25759111
TI  - TBX21 polymorphisms are associated with virus persistence in hepatitis C virus
      infection patients from a high-risk Chinese population.
AB  - Hepatitis C virus (HCV) infection is a major cause of chronic liver disease and
      the varied outcomes of the infection depend on both viral and host factors. We
      have demonstrated that the HCV alternate reading frame protein (F protein) is
      related to Th1/Th2 bias which is involved in virus persistence in chronic
      hepatitis C (CHC) patients. The purpose of this study was to test the hypothesis
      that genetic variants of TBX21 (T cell specific T-box transcription factor) were
      associated with the outcomes of HCV infection and F protein generation. Three
      single nucleotide polymorphisms (SNPs) (rs17250932, rs2074190, rs4794067) in the
      TBX21 gene were genotyped in a case-control study in a cohort of a high-risk
      group, including 354 healthy controls and 747 CHC patients (190 anti-F protein
      antibody seronegative patients and 557 anti-F protein antibody seropositive
      patients). Results showed that the rs4794067 C allele in the TBX21 promoter was
      significantly more common in CHC patients (OR = 1.335, 95% CI = 1.058-1.684, P =
      0.015), exceptionally in anti-F protein seropositive patients (OR = 1.547, 95% CI
      = 1.140-2.101, P = 0.005), compared with healthy controls. And the risk effect
      was also significantly high in patients with HCV 1b genotype and mild fibrosis (P
      = 0.021, P = 0.010, respectively). Compared with the most frequent haplotype TAT,
      haplotype analysis showed that the distribution of TAC was significantly
      different between the chronic HCV carrier group and the healthy group, and so was
      the anti-F antibody seronegativity group and the anti-F antibody seronegativity
      group (all P < 0.001). Our results suggested that TBX21 variants may be involved
      in the etiology of this disease.

PMID- 25759112
TI  - Molecular epidemiology of carbapenemase-producing Escherichia coli and the
      prevalence of ST131 subclone H30 in Shanghai, China.
AB  - The molecular characteristics and epidemiology of carbapenemase-producing
      Escherichia coli (CPEC) isolates from Shanghai, China, were investigated using 21
      imipenem-resistant E. coli isolates obtained from a Shanghai teaching hospital
      from 2011 to 2014. The presence of bla KPC, bla IMP, bla VIM, bla OXA-48, and bla
      NDM was assessed by polymerase chain reaction (PCR) amplification and sequencing.
      CPEC isolates were characterized by the Etest(r), multilocus sequence typing
      (MLST), and pulse-field gel electrophoresis (PFGE). Plasmids carrying resistance
      genes were analyzed by conjugation experiments, replicon typing, plasmid MLST
      (pMLST), S1 nuclease PFGE (S1-PFGE), and Southern hybridization. The genetic
      environment of the resistance genes was determined by PCR and sequencing. Among
      the 21 E. coli isolates, 16 produced carbapenemases; of these, ten isolates
      transferred carbapenemase-encoding plasmids to recipient bacteria. Nine of the 16
      isolates were clonally related, and their PFGE patterns were designated type A.
      ST131 was the predominant sequence type (11 isolates, 68.8 %); the H30 subclone
      comprised 81.8 % of the ST131 strains. In all three isolates, bla IMP-4 was
      located on 50-kb IncN plasmids. All but two bla KPC-2 genes were carried on IncF
      plasmids of various sizes. Hence, both clone-spread and horizontal transfer
      mediated the dissemination of carbapenemase-producing genes in the Shanghai
      isolates.

PMID- 25759113
TI  - Differentiation dynamics of mammary epithelial stem cells from Korean holstein
      dairy cattle under ECM-free conditions.
AB  - The "stem cells" are commonly defined as "cells capable of self-renewal through
      replication and differentiating into specific lineages". The mammary gland
      contains functional stem/progenitor cells. The current study was planned with the
      objectives to study the differentiation dynamics of Korean Holstein mammary
      epithelial stem cells (KHMESCs) under the optimum culture conditions. Lineage
      negative KHMESCs isolated from mammary tissue of lactating cows have shown the
      typical differentiation dynamics with formation of lobulo-alveolar structures in
      in vitro culture. This suggests the existence of bipotential mammary epithelial
      stem cells in the mammary gland. The strong mRNA expression of pluripotency
      factors indicates stemness, whereas expression of milk protein genes and
      epithelial cell-specific gene indicate their differentiation capabilities.
      Further, immunostaining results have shown the differentiation capabilities of
      KHMESCs into both luminal and basal lineages under the extracellular matrix (ECM,
      matrigel) free environment. However, under matrigel, the differentiation process
      was comparatively higher than without matrigel. Immunostaining results also
      suggested that differentiated cells could secrete milk proteins such as beta
      casein. To our knowledge, these data represent the first report on the
      differentiation dynamics and establishment of mammary epithelial stem cells from
      Korean Holstein with typical stemness properties. It was observed that isolated
      KHMESCs had normal morphology, growth pattern, differentiation ability,
      cytogenetic and secretory activity even without ECM. Therefore, it is concluded
      that established KHMESCs could be used for further studies on Korean Holstein
      dairy cows related to lactation studies, as non-GMO animal bioreactors and stem
      cell-based management of bovine mastitis including post-mastitis damage. 

PMID- 25759114
TI  - Effectiveness and predictors of failure of noninvasive mechanical ventilation in
      acute respiratory failure.
AB  - OBJECTIVE: To assess the effectiveness and identify predictors of failure of
      noninvasive ventilation. DESIGN: A retrospective, longitudinal descriptive study
      was made. SETTING: Adult patients with acute respiratory failure. PATIENTS: A
      total of 410 consecutive patients with noninvasive ventilation treated in an
      Intensive Care Unit of a tertiary university hospital from 2006 to 2011.
      PROCEDURES: Noninvasive ventilation. MAIN VARIABLES OF INTEREST: Demographic
      variables and clinical and laboratory test parameters at the start and two hours
      after the start of noninvasive ventilation. Evolution during admission to the
      Unit and until hospital discharge. RESULTS: The failure rate was 50%, with an
      overall mortality rate of 33%. A total of 156 patients had hypoxemic respiratory
      failure, 87 postextubation respiratory failure, 78 exacerbation of chronic
      obstructive pulmonary disease, 61 hypercapnic respiratory failure without chronic
      obstructive pulmonary disease, and 28 had acute pulmonary edema. The failure
      rates were 74%, 54%, 27%, 31% and 21%, respectively. The etiology of respiratory
      failure, serum bilirubin at the start, APACHEII score, radiological findings, the
      need for sedation to tolerate noninvasive ventilation, changes in level of
      consciousness, PaO2/FIO2 ratio, respiratory rate and heart rate from the start
      and two hours after the start of noninvasive ventilation were independently
      associated to failure. CONCLUSIONS: The effectiveness of noninvasive ventilation
      varies according to the etiology of respiratory failure. Its use in hypoxemic
      respiratory failure and postextubation respiratory failure should be assessed
      individually. Predictors of failure could be useful to prevent delayed
      intubation.

PMID- 25759115
TI  - [Reply to the comment on the original: "Survival and neurological prognosis in
      out-hospital cardiorespiratory arrest due to defibrillatable rhythms treated with
      moderate therapeutic hypothermia"].

PMID- 25759116
TI  - Transsphenoidal surgery for malignant pituitary lesions: an analysis of inpatient
      complications.
AB  - BACKGROUND: Fewer than 4% of pituitary tumors are malignant lesions. These tumors
      predominantly represent metastatic disease from elsewhere. This study evaluates
      inpatient complications, demographics, and hospitalization characteristics of
      patients who underwent transsphenoidal surgery (TSS) for malignant pituitary
      lesions. METHODS: The Nationwide Inpatient Sample was evaluated for TSS patients
      from 1998 to 2010. Demographics, hospitalization characteristics, and
      complications were evaluated among patients with malignant lesions and compared
      to those with benign tumors. RESULTS: There were 17,425 inpatient records, 1.0%
      of which involved malignant pituitary tumors. There was no difference in age
      between these cohorts (p = 0.378). Patients with malignant tumors had greater
      length of stay (6.7 days vs 4.5 days, p = 0.003) and higher trending charges
      ($55,371 vs $40,550 p = 0.091). The most common postoperative complications among
      patients with malignant lesions included diabetes insipidus (DI) (17.9%),
      fluid/electrolyte abnormalities (14.0%), neurological complications (5.6%),
      cerebrospinal fluid (CSF) rhinorrhea (2.2%), and iatrogenic pituitary disorders
      (2.2%). Patients with malignant lesions had a significantly greater rates of
      postoperative DI and fluid/electrolyte abnormalities (odds ratio = 2.0 and 1.7,
      respectively), whereas no statistical difference was noted in the rates of CSF
      rhinorrhea (p = 0.372). CONCLUSION: In this analysis of inpatient
      hospitalizations for TSS patients, malignant pituitary disease was associated
      with a greater rate of postoperative DI and fluid/electrolyte abnormalities, but
      no differences in the rates of postoperative CSF rhinorrhea and other
      complications were found. Patients with malignant pituitary lesions undergoing
      TSS had significantly longer hospitalizations and higher trending charges than
      those with benign lesions. This analysis is, however, subject to the limitations
      of the database.

PMID- 25759117
TI  - Rapid proteasomal elimination of 3-hydroxy-3-methylglutaryl-CoA reductase by
      interferon-gamma in primary macrophages requires endogenous 25-hydroxycholesterol
      synthesis.
AB  - Interferons (IFNs) play a central role in immunity and emerging evidence suggests
      that IFN-signalling coordinately regulates sterol biosynthesis in macrophages,
      via Sterol Regulatory Element-Binding Protein (SREBP) dependent and independent
      pathways. However, the precise mechanisms and kinetic steps by which IFN controls
      sterol biosynthesis are as yet not fully understood. Here, we elucidate the
      molecular circuitry governing how IFN controls the first regulated step in the
      mevalonate-sterol pathway, 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR),
      through the synthesis of 25-Hydroxycholesterol (25-HC) from cholesterol by the
      IFN-inducible Cholesterol-25-Hydroxylase (CH25H). We show for the first 30-min of
      IFN stimulation of macrophages the rate of de novo synthesis of the Ch25h
      transcript is markedly increased but by 120-min becomes transcriptionally
      curtailed, coincident with induction of the Activating Transcription Factor 3
      (ATF3) repressor. We demonstrate ATF3 induction by Toll-like receptors is
      strictly dependent on IFN-signalling. While the SREBP-pathway dependent rates of
      de novo transcription of Hmgcr are relatively unchanged in the first 90-min of
      IFN treatment, we find HMGCR enzyme levels undergo a rapid proteasomal-mediated
      degradation, defining a previously unappreciated SREBP-independent mechanism for
      IFN-action. These events precede a sustained marked reduction in Hmgcr RNA levels
      involving SREBP-dependent mechanisms. We demonstrate that HMGCR proteasomal
      degradation by IFN strictly requires the synthesis of endogenous 25-HC and
      functionally couples HMGCR to CH25H to coordinately suppress sterol biosynthesis.
      In conclusion, we quantitatively delineate proteomic and transcriptional levels
      of IFN-mediated control of HMGCR, the primary enzymatic step of the mevalonate
      sterol biosynthesis pathway, providing a foundational framework for
      mathematically modelling the therapeutic outcome of immune-metabolic pathways. 

PMID- 25759119
TI  - Synthesis, anti-inflammatory and anti-ulcer evaluations of thiazole, thiophene,
      pyridine and pyran derivatives derived from androstenedione.
AB  - The reaction of androstenedione with bromine gave the 16-bromo derivative 2. The
      latter reacted with either cyanothioacetamide or thiourea to give the 2
      cyanomethylthiazole derivative 4 and the 2-aminothiazole derivative 13. Compound
      4 and 13 were used underwent some condensation, coupling and heterocyclization
      reactions to give thiophene, pyridine and pyran derivatives. The anti
      inflammatory and anti-ulcer evaluations of the newly synthesized products were
      evaluated and the results showed that 23f showed the maximum antiulcer activity.
      In addition, toxicity of the most active compounds was studied against shrimp
      larvae and showed that compounds 2, 23c and 23f showed non-toxicity against the
      tested organisms. 

PMID- 25759118
TI  - The oxysterol and cholestenoic acid profile of mouse cerebrospinal fluid.
AB  - Oxysterols and cholestenoic acids are oxidised forms of cholesterol with a host
      of biological functions. The possible roles of oxysterols in various neurological
      diseases makes the analysis of these metabolites in the central nervous system of
      particular interest. Here, we report the identification and quantification of a
      panel of twelve sterols in mouse cerebrospinal fluid (CSF) using liquid
      chromatography-mass spectrometry exploiting enzyme assisted derivatisation for
      sterol analysis technology. We found low levels of oxysterols and cholestenoic
      acids in CSF in the range of 5pg/mL-2.6ng/mL. As found in man, these
      concentrations are one to two orders of magnitude lower than in plasma. 

PMID- 25759120
TI  - Five new benzylphenanthrenes from Cremastra appendiculata.
AB  - Five new benzylphenanthrenes, cremaphenanthrenes L-P (1-5) were isolated from the
      EtOAc-soluble extract of the tubers of Cremastra appendiculata. Their structures
      were elucidated based on the spectroscopic data and chemical methods. Compounds 1
      5 were tested in vitro for their cytotoxic effects against colon (HCT-116),
      cervix (Hela), and breast (MCF-7 and MDA-MB-231) cancer cell lines. Compound 1
      showed moderate cytotoxic activities against HCT-116, MCF-7, and MDA-MB-231
      cancer cell lines with IC50 values ranging from 15.84 to 24.18 MUM and weak
      cytotoxicity to Hela cell line with IC50 value of 68.81 MUM.

PMID- 25759121
TI  - Effect of gentiopicroside on experimental acute pancreatitis induced by
      retrograde injection of sodium taurocholate into the biliopancreatic duct in
      rats.
AB  - Gentiopicroside (otherwise known as Gentiopicrin), one of the main active
      ingredients from the traditional Chinese herb medicine Gentiana manshurica Kitag,
      presents the effect of attenuating acute pancreatitis in rats. The experimental
      acute pancreatitis was made by retrograde injection of sodium taurocholate into
      the biliopancreatic duct in rats. Gentiopicroside was given orally and it
      markedly reduced the pancreatitis-evoked increase of serum amylase and lipase
      activity, decreased the pancreas mass/body mass index, tissue water content, TNF
      alpha and IL-1beta concentrations, and attenuated the histopathological changes
      and NF-kappaB p65 protein expression in pancreatic tissue. The results indicate
      that the function of gentiopicroside on acute pancreatitis may be related to
      inhibiting the release of inflammatory mediators and NF-kappaB p65 protein
      expression.

PMID- 25759122
TI  - Triterpene saponins with anti-inflammatory activity from the stems of Entada
      phaseoloides.
AB  - The phytochemical investigation of the ethanol extract from the stems of Entada
      phaseoloides (L.) Merr (also called "Guo Gang Long") led to the isolation of
      eleven triterpene saponins (1-11). Their structures were elucidated by extensive
      spectroscopic methods including 1D- ((1)H and (13)C) and 2D-NMR ((1)H-(1)H COSY,
      HSQC, HMBC, HSQC-TOCSY and ROESY) experiments as well as ESIMS analysis and
      hydrolysis. These saponins comprised entagenic acid as the main aglycon,
      saccharide moieties at C-3 and C-28, and esterification of C-2 or C-3 hydroxyl
      group of the terminal beta-d-glucopyranose unit with a monoterpenic acid. To
      further explain the clinical applications of "Guo Gang Long" for its anti
      inflammatory effect, the inhibitory activities on the production of NO of the
      saponins and the related aglycon, entagenic acid (12), were evaluated in vitro.
      The compounds containing a free hydroxyl at C-3 of aglycon (1 and 4) and
      entagenic acid showed significant activities against NO production in
      lipopolysaccharide-stimulated mouse macrophage RAW264.7 cells with IC50 values of
      25.08, 20.13 and 23.48 MUM, respectively. And the three compounds could also
      inhibit the release of pro-inflammatory cytokines, such as TNF-alpha, IL-1beta,
      IL-6 and IL-8.

PMID- 25759123
TI  - Corrigendum: the antimicrobial peptide LL37 is a T-cell autoantigen in psoriasis.

PMID- 25759124
TI  - Endoscopic high-intensity focused US: technical aspects and studies in an in vivo
      porcine model (with video).
AB  - BACKGROUND: High-intensity focused US (HIFU) is becoming more widely used for
      noninvasive and minimally invasive ablation of benign and malignant tumors.
      Recent studies suggest that HIFU can also enhance targeted drug delivery and
      stimulate an antitumor immune response in many tumors. However, targeting
      pancreatic and liver tumors by using an extracorporeal source is challenging due
      to the lack of an adequate acoustic window. The development of an EUS-guided HIFU
      transducer has many potential benefits including improved targeting, decreased
      energy requirements, and decreased potential for injury to intervening
      structures. OBJECTIVE: To design, develop, and test an EUS-guided HIFU transducer
      for endoscopic applications. DESIGN: A preclinical, pilot characterization and
      feasibility study. SETTING: Academic research center. PATIENTS: Studies were
      performed in an in vivo porcine model. INTERVENTION: Thermal ablation of in vivo
      porcine pancreas and liver was performed with EUS-guided focused US through the
      gastric tract. RESULTS: The transducer successfully created lesions in gel
      phantoms and ex vivo bovine livers. In vivo studies demonstrated that targeting
      and creating lesions in the porcine pancreas and liver are feasible. LIMITATIONS:
      This was a preclinical, single-center feasibility study with a limited number of
      subjects. CONCLUSION: An EUS-guided HIFU transducer was successfully designed and
      developed with dimensions that are appropriate for endoscopic use. The
      feasibility of performing EUS-guided HIFU ablation in vivo was demonstrated in an
      in vivo porcine model. Further development of this technology will allow
      endoscopists to perform precise therapeutic ablation of periluminal lesions
      without breaching the wall of the gastric tract.

PMID- 25759125
TI  - Reactivation of persistent Epstein-Barr virus (EBV) causes secretion of
      thyrotropin receptor antibodies (TRAbs) in EBV-infected B lymphocytes with TRAbs
      on their surface.
AB  - Epstein-Barr virus (EBV) is a ubiquitous virus that infects most adults latently.
      It persists in B lymphocytes and reactivates occasionally. Graves' disease is an
      autoimmune hyperthyroidism caused by thyrotropin receptor antibodies (TRAbs). We
      have reported that Graves' disease patients and healthy controls have EBV
      infected lymphocytes that have TRAbs on their surface (TRAb(+)EBV(+) cells) in
      peripheral blood mononuclear cells (PBMCs). EBV reactivation is known to be
      associated with plasma cell differentiation and antibody production of B cells.
      In this study, we investigated whether TRAb(+)EBV(+) cells really produce TRAbs
      or not when persistent EBV is reactivated. We cultured PBMCs from 12 Graves'
      disease patients and 12 healthy controls for several days with cyclosporine A to
      expand the EBV-infected cell population, and then compared TRAb levels between
      EBV reactivation by 33  degrees C culture and EBV nonreactivation by 37  degrees
      C culture of PBMCs. Flow cytometry confirmed that all samples at day 0
      (reactivation starting point) contained TRAb(+)EBV(+) cells. During 33  degrees C
      culture, EBV-reactivated cells with EBV-gp350/220 expression increased from about
      1 to 4%. We quantified TRAb levels in culture fluids by radio-receptor assay, and
      detected an increased concentration for at least one sampling point at 33 
      degrees C (from days 0 to 12) for all patients and healthy controls. TRAb levels
      were significantly higher in supernatants of 33  degrees C culture than of 37 
      degrees C culture, and also significantly higher in supernatants from patients
      than those from controls. This study revealed TRAb production from TRAb(+)EBV(+)
      cells in response to reactivation induction of persistent EBV in different
      efficiencies between patients and controls. 

PMID- 25759126
TI  - Is longer better?

PMID- 25759127
TI  - The unique challenges of hemovigilance for pediatric patients.

PMID- 25759128
TI  - Transfusion medicine illustrated: An unusual case of near-fatal hemolytic anemia
      treated with erythrocytapheresis and therapeutic plasma exchange.

PMID- 25759130
TI  - Response to letter to the editor.

PMID- 25759131
TI  - Effect of failure/success feedback and the moderating influence of personality on
      reward motivation.
AB  - While motivation to pursue goals is often assumed to be a trait-like
      characteristic, it is influenced by a variety of situational factors. In
      particular, recent experiences of success or failure, as well as cognitive
      responses to these outcomes, may shape subsequent willingness to expend effort
      for future rewards. To date, however, these effects have not been explicitly
      tested. In the present study, 131 healthy individuals received either failure or
      success feedback on a cognitive task. They were then instructed to either
      ruminate or distract themselves from their emotions. Finally, they completed the
      Effort Expenditure for Rewards Task, a laboratory measure of reward motivation.
      Results indicate that participants who received failure feedback relied more
      strongly on the reward magnitude when choosing whether to exert greater effort to
      obtain larger rewards, though this effect only held under conditions of
      significant uncertainty about whether the effort would be rewarded. Further,
      participants with high levels of trait inhibition were less responsive to reward
      value and probability when choosing whether to expend greater effort, results
      that echo past studies of effort-based decision-making in psychological
      disorders. 

PMID- 25759132
TI  - Focal myositis: Sonographic findings.

PMID- 25759133
TI  - A lycopene beta-cyclase/lycopene epsilon-cyclase/light-harvesting complex-fusion
      protein from the green alga Ostreococcus lucimarinus can be modified to produce
      alpha-carotene and beta-carotene at different ratios.
AB  - Biosynthesis of asymmetric carotenoids such as alpha-carotene and lutein in
      plants and green algae involves the two enzymes lycopene beta-cyclase (LCYB) and
      lycopene epsilon-cyclase (LCYE). The two cyclases are closely related and
      probably resulted from an ancient gene duplication. While in most plants
      investigated so far the two cyclases are encoded by separate genes, prasinophyte
      algae of the order Mamiellales contain a single gene encoding a fusion protein
      comprised of LCYB, LCYE and a C-terminal light-harvesting complex (LHC) domain.
      Here we show that the lycopene cyclase fusion protein from Ostreococcus
      lucimarinus catalyzed the simultaneous formation of alpha-carotene and beta
      carotene when heterologously expressed in Escherichia coli. The stoichiometry of
      the two products in E. coli could be altered by gradual truncation of the C
      terminus, suggesting that the LHC domain may be involved in modulating the
      relative activities of the two cyclase domains in the algae. Partial deletions of
      the linker region between the cyclase domains or replacement of one or both
      cyclase domains with the corresponding cyclases from the green alga Chlamydomonas
      reinhardtii resulted in pronounced shifts of the alpha-carotene-to-beta-carotene
      ratio, indicating that both the relative activities of the cyclase domains and
      the overall structure of the fusion protein have a strong impact on the product
      stoichiometry. The possibility to tune the product ratio of the lycopene cyclase
      fusion protein from Mamiellales renders it useful for the biotechnological
      production of the asymmetric carotenoids alpha-carotene or lutein in bacteria or
      fungi. 

PMID- 25759134
TI  - DNA/RNA chimera templates improve the emission intensity and target the
      accessibility of silver nanocluster-based sensors for human microRNA detection.
AB  - In recent years microRNAs (miRNAs) have been established as important biomarkers
      in a variety of diseases including cancer, diabetes, cardiovascular disease,
      aging, Alzheimer's disease, asthma, autoimmune disease and liver diseases. As a
      consequence, a variety of monitoring methods for miRNAs have been developed,
      including a fast and simple method for miRNA detection by exploitation of the
      unique photoluminescence of DNA-templated silver nanoclusters (DNA/AgNCs). To
      increase the versatility of the AgNC-based method, we have adopted DNA/RNA
      chimera templates for AgNC-based probes, allowing response from several human
      miRNAs which are hardly detectable with DNA-based probes. Here, we demonstrate in
      detail the power of DNA/RNA chimera/AgNC probes in detecting two human miRNAs,
      let-7a and miR-200c. The DNA/RNA chimera-based probes are highly efficient to
      determine the level of miRNAs in several human cell lines. 

PMID- 25759135
TI  - Authors' reply to Kremer and Van de Perre.

PMID- 25759137
TI  - Multilocus sequence typing analysis of Cronobacter spp. isolated from China.
AB  - Multilocus sequence typing (MLST) has proven to be an effective approach for the
      subtyping isolates of the Cronobacter genus and to exhibit a high level of
      discrimination between isolates. In this study, 151 Cronobacter strains were
      isolated from different sources and provinces across China from 2010 to 2012 and
      analyzed by MLST. Their sequence type profiles were compared with strains from
      other countries which were widely geographically and temporally distributed. Out
      of 151 strains in this study, the majority of strains were Cronobacter sakazakii
      (70.9 %), C. malonaticus (15.9 %), C. dublinensis (10.6 %), C. turicensis (2.0
      %), and C. muytjensii (0.7 %). The strains were divided into 85 sequence types
      (STs), among which only 17 had previously been reported in other countries. The
      85 identified STs for the Cronobacter genus were grouped into 14 clonal complexes
      and 47 singletons according to eBURST algorithm. The Cronobacter isolated from
      China showed a high diversity when they were subtyped using the MLST method. When
      compared to the Cronobacter PubMLST database, some sequence types of strains
      cultured from food and/or water in this study were also the same with strains
      isolated from patients in other countries as reported previously. This result
      showed the potential hazard of strains contaminating water and weaning food from
      China.

PMID- 25759136
TI  - Species-specific duplications driving the recent expansion of NBS-LRR genes in
      five Rosaceae species.
AB  - BACKGROUND: Disease resistance (R) genes from different Rosaceae species have
      been identified by map-based cloning for resistance breeding. However, there are
      few reports describing the pattern of R-gene evolution in Rosaceae species
      because several Rosaceae genome sequences have only recently become available.
      RESULTS: Since most disease resistance genes encode NBS-LRR proteins, we
      performed a systematic genome-wide survey of NBS-LRR genes between five Rosaceae
      species, namely Fragaria vesca (strawberry), Malus * domestica (apple), Pyrus
      bretschneideri (pear), Prunus persica (peach) and Prunus mume (mei) which
      contained 144, 748, 469, 354 and 352 NBS-LRR genes, respectively. A high
      proportion of multi-genes and similar Ks peaks (Ks = 0.1- 0.2) of gene families
      in the four woody genomes were detected. A total of 385 species-specific
      duplicate clades were observed in the phylogenetic tree constructed using all
      2067 NBS-LRR genes. High percentages of NBS-LRR genes derived from species
      specific duplication were found among the five genomes (61.81% in strawberry,
      66.04% in apple, 48.61% in pear, 37.01% in peach and 40.05% in mei). Furthermore,
      the Ks and Ka/Ks values of TIR-NBS-LRR genes (TNLs) were significantly greater
      than those of non-TIR-NBS-LRR genes (non-TNLs), and most of the NBS-LRRs had
      Ka/Ks ratios less than 1, suggesting that they were evolving under a
      subfunctionalization model driven by purifying selection. CONCLUSIONS: Our
      results indicate that recent duplications played an important role in the
      evolution of NBS-LRR genes in the four woody perennial Rosaceae species. Based on
      the phylogenetic tree produced, it could be inferred that species-specific
      duplication has mainly contributed to the expansion of NBS-LRR genes in the five
      Rosaceae species. In addition, the Ks and Ka/Ks ratios suggest that the rapidly
      evolved TNLs have different evolutionary patterns to adapt to different pathogens
      compared with non-TNL resistant genes.

PMID- 25759138
TI  - Pre-incarceration HIV risk behaviours of male and female inmates.
AB  - In most countries, HIV and AIDS rates are higher among inmates than in the
      general population. As part of a series of studies aimed at examining the
      plausible links between HIV and incarceration in a State prison system in the
      United States (US), the present study examined pre-incarceration sexual and
      injection drug use behaviours of inmates and their demographic correlates. Two
      hundred-andsixteen female and 260 male inmates randomly selected from 17 Illinois
      State prisons completed a structured questionnaire. Findings indicate that the
      rate of inconsistent condom use with multiple anal and vaginal sexual partners
      among study participants ranged from 11 to 49%. Fourteen per cent of the women
      and 25% of the men reported ever injecting drugs, while 13% of the women and 7%
      of the men had ever shared needles. Demographic correlates of risk behaviours
      differed between gender and for specific behaviours. The findings indicate that
      persons entering prison generally exhibit risk behaviours that may increase their
      chances of acquiring HIV. Comprehensive HIV prevention programmes should be made
      available to inmates in US prisons and be accessible to them upon release.
      Studies are needed to examine how individual and structural factors interact to
      increase HIV and incarceration risk. 

PMID- 25759139
TI  - Exploring prison buprenorphine misuse in the United Kingdom: a qualitative study
      of former prisoners.
AB  - The United Kingdom Ministry of Justice recently highlighted the extent of
      buprenorphine (Subutex) misuse in English andWelsh prisons, naming it the third
      most misused drug overall. Yet little is known regarding how illicit
      buprenorphine is obtained in prison and what influences prisoners to use it.
      Qualitative research was used to explore prison drug using practices. Thirty men
      who were former prisoners with a history of injecting drug use were interviewed
      in depth about their illicit prison drug use, including buprenorphine. Interviews
      were conducted over 18 months, from August 2006 to January 2008 and were analysed
      using Framework. The misuse of Subutex by snorting emerged as a significant
      theme. Accounts suggested that the diversion of prison prescribed Subutex was
      widespread and prisoners used various tactics to obtain the medication. Various
      complex and interlinked reasons were given to explain why Subutex was snorted in
      prison. The main motivation for snorting was to experience a prolonged euphoric
      opiate effect, believed to help to combat the boredom of being in prison. The
      price of illicit Subutex in prison was linked to its availability, but it was
      generally cheaper than heroin, thus contributing to its use.
      Participants'narratives identified the belief that snorting Subutex in prison was
      not risk free, but risks were lower than continuing to use other drugs,
      particularly injecting illicit opiates. The implications of prison Subutex misuse
      for prisoners, prison medical services, commissioners, and prescribing policy and
      practice are discussed. 

PMID- 25759140
TI  - Prevalence of psychiatric morbidity among inmates of a borstal institution in
      Nigeria.
AB  - Studies have reported increased psychiatric morbidity among young detainees, with
      as many as three-quarters reported to have one or more psychiatric disorders.
      Despite this, however, there is a dearth of published work among young inmates of
      prisons, remand homes or borstal institutions in Nigeria. The aim of this study
      was to assess possible psychiatric morbidity among young inmates of a borstal
      institution in Nigeria and to determine the factors that may be associated with
      this morbidity. Fifty-three inmates of one of the two existing borstal
      institution in Nigeria were assessed for psychiatric morbidity using the 12-item
      General Health Questionnaire (GHQ-12). The GHQ-12 scores were compared with the
      socio-demographic factors of the respondents. Twenty-eight (52.8%) of the inmates
      were over 18 years old, 35.8% were in the middle position within the family,
      62.3% were of Christian faith, and 64.2% had their parents still living together.
      Seventeen (32.1%) of the inmates were from Hausa ethnic extraction, 58.5% stayed
      for more than 6 months at the borstal institution, and 81.1% were brought to the
      institution by their parents. The mean age of the inmates was 17.3 years (range,
      14-23 years) and 26 (49.1%) of them were GHQ-positive. There was no statistically
      significant difference between the mean age of GHQ-positive and GHQ-negative
      inmates (F=1.73, p=0.19), and none of the socio-demographic variables were
      significantly associated with psychiatric morbidity (i.e. GHQ-12 positivity). The
      study observed a high prevalence of undetected psychiatric morbidity among
      inmates at the borstal institution. Efforts should be intensified by the
      authority responsible for managing the Nigerian prison services (including the
      borstal institutions) to improve mental health services. 

PMID- 25759141
TI  - The development of participatory health research among incarcerated women in a
      Canadian prison.
AB  - This paper describes the development of a unique prison participatory research
      project, in which incarcerated women formed a research team, the research
      activities and the lessons learned. The participatory action research project was
      conducted in the main short sentence minimum/medium security women's prison
      located in a Western Canadian province. An ethnographic multi-method approach was
      used for data collection and analysis. Quantitative data was collected by surveys
      and analysed using descriptive statistics. Qualitative data was collected from
      orientation package entries, audio recordings, and written archives of research
      team discussions, forums and debriefings, and presentations. These data and
      ethnographic observations were transcribed and analysed using iterative and
      interpretative qualitative methods and NVivo 7 software. Up to 15 women worked
      each day as prison research team members; a total of 190 women participated at
      some time in the project between November 2005 and August 2007. Incarcerated
      women peer researchers developed the research processes including opportunities
      for them to develop leadership and technical skills. Through these processes,
      including data collection and analysis, nine health goals emerged. Lessons
      learned from the research processes were confirmed by the common themes that
      emerged from thematic analysis of the research activity data. Incarceration
      provides a unique opportunity for engagement of women as expert partners
      alongside academic researchers and primary care workers in participatory research
      processes to improve their health. 

PMID- 25759142
TI  - Vocal divergence and discrimination of long calls in tamarins: A comparison of
      allopatric populations of Saguinus fuscicollis nigrifrons and S. f. lagonotus.
AB  - Divergence in vocalizations can reduce gene flow by serving as a premating
      barrier during secondary contact between previously isolated populations. In
      primates, vocal divergence in long calls of separated populations has been
      documented, yet recognition of these differences by the respective populations
      has seldom been studied in the field. To investigate this issue, we studied
      populations of two subspecies of saddle-back tamarins (Saguinus fuscicollis
      nigrifrons and S. f. lagonotus) that are separated by the Amazon River in Peru.
      We recorded long calls of each subspecies and detected significant differences
      between the populations in the number of notes per call, duration of calls, and
      shifts in starting frequency of notes over the length of calls. In addition, a
      population of S. f. nigrifrons responded more overtly in measures of approach to
      playback of long calls of its own subspecies compared to long calls of S. f.
      lagonotus. These results are consistent with the hypothesis that allopatric
      divergence of long calls might contribute to reproductive isolation of these
      subspecies of saddle-back tamarins, which adds to growing evidence suggesting
      full species status for these taxa.

PMID- 25759143
TI  - Dissection of keratin network formation, turnover and reorganization in living
      murine embryos.
AB  - Epithelial functions are fundamentally determined by cytoskeletal keratin network
      organization. However, our understanding of keratin network plasticity is only
      based on analyses of cultured cells overexpressing fluorescently tagged keratins.
      In order to learn how keratin network organization is affected by various signals
      in functional epithelial tissues in vivo, we generated a knock-in mouse that
      produces fluorescence-tagged keratin 8. Homozygous keratin 8-YFP knock-in mice
      develop normally and show the expected expression of the fluorescent keratin
      network both in fixed and in vital tissues. In developing embryos, we observe for
      the first time de novo keratin network biogenesis in close proximity to
      desmosomal adhesion sites, keratin turnover in interphase cells and keratin
      rearrangements in dividing cells at subcellular resolution during formation of
      the first epithelial tissue. This mouse model will help to further dissect
      keratin network dynamics in its native tissue context during physiological and
      also pathological events. 

PMID- 25759144
TI  - Imputing Missing Race/Ethnicity in Pediatric Electronic Health Records: Reducing
      Bias with Use of U.S. Census Location and Surname Data.
AB  - OBJECTIVE: To assess the utility of imputing race/ethnicity using U.S. Census
      race/ethnicity, residential address, and surname information compared to standard
      missing data methods in a pediatric cohort. DATA SOURCES/STUDY SETTING:
      Electronic health record data from 30 pediatric practices with known
      race/ethnicity. STUDY DESIGN: In a simulation experiment, we constructed
      dichotomous and continuous outcomes with pre-specified associations with known
      race/ethnicity. Bias was introduced by nonrandomly setting race/ethnicity to
      missing. We compared typical methods for handling missing race/ethnicity
      (multiple imputation alone with clinical factors, complete case analysis,
      indicator variables) to multiple imputation incorporating surname and address
      information. PRINCIPAL FINDINGS: Imputation using U.S. Census information reduced
      bias for both continuous and dichotomous outcomes. CONCLUSIONS: The new method
      reduces bias when race/ethnicity is partially, nonrandomly missing.

PMID- 25759145
TI  - ATM gene single nucleotide polymorphisms predict regimen-related gastrointestinal
      toxicity in patients allografted after reduced conditioning.
AB  - Polymorphisms of genes involved in innate and adaptive immunity have become an
      object of major interest in regard to hematopoietic stem cell transplantation
      (HSCT) complications. Regimen-related gastrointestinal toxicity (RR-GIT) is the
      dominant complication during the pre-engraftment period and has been linked to
      increased risk of graft-versus-host disease (GVHD) development. According to our
      hypothesis, functional variants of genes participating in DNA damage response
      (DDR) may have an impact on the extent of tissue damage caused by the
      conditioning regimen. In our single-center study, we analyzed 62 patients who
      underwent HSCT from HLA-identical donors after reduced conditioning. The patients
      were genotyped for 5 single nucleotide polymorphisms (SNPs, rs4585 T/G, rs189037
      A/G, rs227092 T/G, rs228590 C/T, and rs664677 T/C) of the ATM gene-the essential
      member of the DDR pathways, using allele-specific matrix-assisted laser
      desorption/ionization, time-of-flight (MALDI-TOF) mass spectrometry assay.
      Because of almost absolute linkage disequilibrium observed among all 5 SNPs,
      association of 2 major ATM haplotypes (ATM1/ATM2) with RR-GIT and acute GVHD
      (aGVHD) was analyzed. Importantly, the univariate and multivariate analysis
      showed that patients homozygous for ATM2 haplotype (rs4585*T, rs189037*A,
      rs227092*T, rs228590*C, and rs664677*T) are more likely to suffer from high-grade
      RR-GIT than ATM1 homozygous patients. The association with aGVHD was not
      significant. To our knowledge, this is the first report showing the ATM gene
      variability in relation to RR-GIT in the allogeneic HSCT setting. 

PMID- 25759147
TI  - Abstracts of the 11th Annual Congress of the European Cardiac Arrhythmia Society,
      April 19-21, 2015, Paris, France.

PMID- 25759146
TI  - Circulating angiogenic factors associated with response and survival in patients
      with acute graft-versus-host disease: results from Blood and Marrow Transplant
      Clinical Trials Network 0302 and 0802.
AB  - Circulating angiogenic factors (AF) reflect tissue healing capacity, although
      some AF can also contribute to inflammation and are indicative of endothelial
      dysfunction. The AF milieu in acute graft-versus-host disease (aGVHD) has not
      been broadly characterized. We hypothesized that patients with abundant AF
      involved in repair/regeneration versus those mediating damage/inflammation would
      have improved outcomes. Circulating AF known predominantly for
      repair/regeneration (epidermal growth factor [EGF], fibroblast growth factor-1
      and -2, heparin binding-EGF-like growth factor, and vascular endothelial growth
      factor-A [VEGF-A], -C, and -D) and for damage/inflammation (angiopoietin-2,
      endothelin-1, soluble endoglin [sEng], follistatin [FS], leptin, and placental
      growth factor [PlGF]) were measured in a discovery set of hematopoietic cell
      recipients with grade III and IV aGVHD and compared with controls, then validated
      in 2 aGVHD cohorts enrolled in Blood and Marrow Transplant Clinical Trials
      Network (BMT CTN) trials 0302 (n = 105, serum) and 0802 (n = 158, plasma) versus
      controls without aGVHD (n = 53, serum). Levels of EGF and VEGF-A were lower than
      in controls at the onset of aGVHD in both trials and higher with complete
      response to first-line aGVHD therapy in CTN 0802. FS and PlGF were elevated in
      aGVHD measured in either serum or plasma. At day 28 after initial aGVHD therapy,
      elevated FS was an independent negative prognostic factor for survival in both
      cohorts (hazard ratio, 9.3 in CTN 0302; 2.8 in CTN 0802). These data suggest that
      circulating AF are associated with clinical outcomes after aGVHD and, thus, may
      contribute to both pathogenesis and recovery. 

PMID- 25759148
TI  - Therapists' perceptions of social media and video game technologies in upper limb
      rehabilitation.
AB  - BACKGROUND: The application of technologies, such as video gaming and social
      media for rehabilitation, is garnering interest in the medical field. However,
      little research has examined clinicians' perspectives regarding technology
      adoption by their clients. OBJECTIVE: The objective of our study was to explore
      therapists' perceptions of how young people and adults with hemiplegia use gaming
      and social media technologies in daily life and in rehabilitation, and to
      identify barriers to using these technologies in rehabilitation. METHODS: We
      conducted two focus groups comprised of ten occupational
      therapists/physiotherapists who provide neurorehabilitation to individuals with
      hemiplegia secondary to stroke or cerebral palsy. Data was analyzed using
      inductive thematic analysis. The diffusion of innovations theory provided a
      framework to interpret emerging themes. RESULTS: Therapists were using technology
      in a limited capacity. They identified barriers to using social media and gaming
      technology with their clients, including a lack of age appropriateness, privacy
      issues with social media, limited transfer of training, and a lack of
      accessibility of current systems. Therapists also questioned their role in the
      context of technology-based interventions. The opportunity for social interaction
      was perceived as a major benefit of integrated gaming and social media.
      CONCLUSIONS: This study reveals the complexities associated with adopting new
      technologies in clinical practice, including the need to consider both client and
      clinician factors. Despite reporting several challenges with applying gaming and
      social media technology with clinical populations, therapists identified
      opportunities for increased social interactions and were willing to help shape
      the development of an upper limb training system that could more readily meet the
      needs of clients with hemiplegia. By considering the needs of both therapists and
      clients, technology developers may increase the likelihood that clinicians will
      adopt innovative technologies.

PMID- 25759149
TI  - Interactive computer play - what happens when the game is over?

PMID- 25759150
TI  - A study on the effects of general fatigue on head and neck proprioception in
      healthy young adults.
AB  - BACKGROUND: Fatigue is one of the factors causing disturbance in proprioception
      which can be manifested in two ways: general and local. Due to the important role
      of cervical proprioception on body stability and posture, research on the effects
      of general fatigue on proprioception helps to better understand its mechanism and
      to improve the strategies to prevent injury. Therefore, the aim of this study was
      to identify the effects of general fatigue on head and neck proprioception in
      young healthy adults. MATERIAL AND METHODS: This clinical study was done by
      implementing pre- and post-test measurements in 112 young healthy subjects aged
      between 18-30 years and able to walk at a speed of 10Km for 5 minutes. They were
      randomly divided into an experimental and control group. The patients in the
      control (not exposed to a general fatigue task) and experimental (exposed to a
      general fatigue task) groups were matched for age, height and weight. In the
      first step, the zero absolute reposition angle of the head and neck was measured
      in all participants. Then the subjects in the experimental group did a five
      minute run on the treadmill to achieve the level of general fatigue, following
      which the head and neck reproduction angle was measured in all subjects for the
      second time. RESULTS: There was a statistical significant difference between pre-
      and post-test absolute angular error in the experimental group; however, there
      was no noticeable difference between the pre- and post-test data in the control
      group. CONCLUSIONS: 1. General fatigue increased the repositioning angular error
      of head and neck. 2. Neck proprioception decreased due to general fatigue. 3.
      General fatigue increased the risk of neck injury.

PMID- 25759151
TI  - Anterior fixation of thoracolumbar traumatic spinal injuries.
AB  - BACKGROUND: Traumatic spinal fractures require surgical treatment to restore the
      anatomical curvatures of the spine and release the nervous structures. However,
      uniform management guidelines have not been established and thus the literature
      includes papers focussing only on the posterior techniques as well as those
      assessing the anterior or anteroposterior approaches. This paper presents the
      outcomes of the treatment of spinal fractures with anterior and anteroposterior
      fixation. MATERIAL AND METHODS: The study enrolled 48 patients. The age of the
      patients at the time of injury was 36.8 years on average and the mean follow-up
      period was 3.8 years. All the fractures were unstable and caused stenosis of the
      spinal canal lumen. We used anterior or combined anterior and posterior
      approaches with a titanium implant in all the cases. Radiological assessment
      involved determination of the monosegmental and bisegmental Cobb angle, and the
      neurological status was evaluated according to the Frankel classification.
      RESULTS: The mean post-traumatic monosegmental angle was -17.1 degrees , compared
      to -9.1 degrees  post-operatively and -9.2 degrees  at followup. The bisegmental
      angle was -12.7 degrees  at baseline, -7.9 degrees  post-operatively, and -8
      degrees  in the follow-up period. Neurological assessment showed no neurological
      deficits in 27 patients while 2 persons had complete limb paralysis and the other
      19 patients had various degrees of neurological deficits. The last follow-up
      examination did not show any improvement with respect to the neurological status
      of the patients with complete paralysis. However, an improvement of at least 1
      Frankel group was noted in 15 patients with partial neurological deficits.
      CONCLUSIONS: 1. The most common causes of traumatic spinal injuries are falls
      from a height and road accidents. 2. fractures occur most often at the
      thoracolumbar junction of the spine. 2. Anteroposterior fixation with release of
      the spinal canal and spinal fusion is a beneficial treatment method. 3. Apart
      from vertebral body mesh, treating lumbar spine fractures requires the additional
      use of vertebral body screws or transpedicular posterior fixation. 4. Anterior
      fixation ensures the restoration of the physiological curvatures of the spine and
      stabilizes the spine until a complete bone union is achieved, preventing the loss
      of correction during the follow-up period.

PMID- 25759152
TI  - Evaluation of the results of management of frozen shoulder using the arthroscopic
      capsular release.
AB  - BACKGROUND: The aim of treatment of frozen shoulder is to regain a painless and
      functional shoulder range of shoulder motion. In this study we evaluated the
      results of using the arthroscopic technique for the release of the shoulder joint
      capsule in patients with a diagnosis of frozen shoulder. MATERIAL AND METHODS:
      The study included 40 patients with frozen shoulder. They were operated upon with
      the use of electrocautery for the release of the shoulder joint capsule. The
      group consisted of 29 women and 11 men with a mean age of 48.2 years (range 38
      62). RESULTS: Preoperatively, the mean Constant and Murly shoulder score was
      36.35 (range 21-51). At the end of the follow up period, the mean score was 85.8
      (range 62 to 98). The difference between the means of pre- and postoperative
      total score was statistically significant (t =10.85 and p=0.0001). 22 patients
      (55%) had excellent results, 14 patients (35%) had good results, 4 patients (10%)
      had fair results and none had poor results. The 4 cases with fair results were
      all female, all had insulin-dependent diabetes mellitus and were > 50 years old.
      CONCLUSIONS: 1. Arthroscopic capsular release is an effective and safe method for
      the treatment of refractory frozen shoulder. 2. It achieves dramatic pain and
      motion improvement post-operatively, allowing very early postoperative
      rehabilitation.

PMID- 25759153
TI  - Postoperative migration of short stem prosthesis of the hip joint.
AB  - BACKGROUND: Hip replacement surgery is a popular procedure that provides
      predictable, long-lasting and good effects. The use of short stem prostheses
      helps preserve an intact medullary cavity and proximal diaphysis. It has been
      demonstrated that the use of short stem prostheses leads to better clinical
      results compared to standard stem prostheses. The study aimed to assess the
      migration of the stem of the Proxima hip prosthesis. Migration was defined as a
      change in the angle of stem position towards a varus deformity. MATERIAL AND
      METHODS: The study involved 164 patients (83 women, 81 men) who underwent hip
      replacement surgery with a total of 185 Proxima prostheses in the Cracow
      Rehabilitation Centre between 2007 and 2012. RESULTS: Radiographic analysis
      included a series of three radiographs obtained for each patient on Day 0 and
      after 6 and 12 months. Stem migration towards a varus deformity was reported
      during the follow-up period. There was a correlation between the change in the
      angle of varus prosthesis alignment and the length of follow-up. The mean change
      of the varus angle was 8.21 degrees  after 12 months. There was a statistically
      significant difference in the angle of the varus prosthesis alignment between the
      sexes. After 12 months the total change was 6.82 degrees  in women and 9.65
      degrees  in men. There was no significant correlation between a patient's BMI,
      age, the total length of the neck of the implant and the progression of the angle
      of varus prosthesis alignment. CONCLUSIONS: 1. The greatest displacement of the
      Proxima short stem implant towards a varus deformity is seen within the first 6
      months following implantation. 2. The change of the angle of varus prosthesis
      alignment depends on the initial positioning of the prosthesis and the sex of the
      patient. 3. The change of the angle of varus prosthesis alignment is independent
      from the patient's age and BMI.

PMID- 25759154
TI  - Gait analysis in patients after unilateral hip arthroplasty.
AB  - BACKGROUND: Osteoarthritis (OA) is the most common joint pathology and the main
      cause of disability in elderly persons. Arthroplasty still remains the most
      effective treatment of OA. Routine post-operative patient assessment does not
      include an objective functional examination leading to conclusions regarding the
      need of further rehabilitation. This role is played by gait analysis performed in
      patients after arthroplasty. The aim of the study was to conduct a quantitative
      and qualitative analysis of selected gait parameters in patients after unilateral
      cementless hip arthroplasty. MATERIAL AND METHODS: The study involved a group of
      16 patients who were examined before and after hip arthroplasty. Gait analysis
      was conducted before surgery and at least 6 months after the procedure. The Smart
      DX BTS system for spatial gait analysis was used. RESULTS: The duration of the
      stance phase on the affected side was 63.8 [% gait cycle] and was significantly
      shorter (p<0.05) than the phase on the unaffected side, with a duration of 69.4
      [% gait cycle]. After surgery, the duration of swing phase on the unaffected side
      increased (p<0.05) from 30.6 to 35.1 [% gait cycle]. A statistically significant
      change was also found in the double support phase (the arthrotic limb as the
      front limb), which was markedly shortened. The average length of a single and
      double step, cadence, average gait velocity, and the velocity of leg swing in the
      swing phase increased. The range of hip mobility increased in all planes,
      especially in the sagittal plane. CONCLUSION: The space and time gait parameters
      with regard to the operated leg after hip arthroplasty indicate an improvement as
      compared with the baseline results; however, they do not reach the values found
      in healthy persons.

PMID- 25759155
TI  - Evaluation of differences between two groups of low back pain patients with and
      without rotational demand activities based on hip and lumbopelvic movement
      patterns.
AB  - BACKGROUND: Excessive and earlier lumbopelvic motions during trunk and limb
      movements tests have been reported in both low back pain (LBP) patients with and
      without trunk and hip rotational demand activities. The aim of the present study
      was to determine differences in hip and lumbopelvic rotation during the active
      hip internal rotation (AHIR) test between two groups of LBP patients with and
      without regular trunk and hip rotational demand activities. MATERIAL AND METHODS:
      A total of 35 LBP patients, including 15 males who regularly participated in
      rotational demand sports activities and 20 males not participating in sports and
      functional rotational demand activities, participated in study. The AHIR test was
      performed. The kinematic variables of hip and pelvic rotations were recorded by a
      Qualisys motion analysis system. Pelvic and hip rotations were calculated across
      time during the test. In addition, pelvic rotations in the first half of the test
      and pelvic-hip timing were calculated. RESULTS: People with rotational demand
      activities had a higher pelvic rotation both during the test and in the first 50%
      of movement. Earlier pelvic rotation was observed in people with rotational
      demand activities compared to people with non-rotational demand activities.
      CONCLUSION: 1. The data of the current study suggests that lumbopelvic movement
      patterns in different groups of LBP patients in regard to their specific
      activities may vary. 2. LBP people with rotational demand sports activities have
      a greater tendency of pelvic rotation motion during the AHIR.

PMID- 25759156
TI  - Cost-effectiveness analysis of treatment of osteoporotic fractures in relation to
      FRAX algorithm in a sample of Polish population.
AB  - BACKGROUND: The increasing incidence of osteoporotic fractures is becoming a
      growing burden on the health service. Due to the high cost of treatment, these
      fractures require a broader look at the underlying problem. The aim of the study
      was to assess the 10-year probability of hip fracture or any other major
      osteoporotic fracture at which the treatment becomes cost-effective. MATERIAL AND
      METHODS: This was a retrospective study of a group of 1,024 patients. The cost
      effectiveness of pharmacological low-energy fracture prevention was analyzed by
      means of the medication defined as the reimbursement limit basis in the
      reimbursement limit group 147.0. (medications used in bone diseases) in July 2013
      (Alendrogen 70 mg). 3- and 5-year therapies were analysed. The outcome was
      compared with the results of FRAX(r) (of the Polish and British population) in
      every patient. RESULTS: The model for calculating cost-effectiveness showed that
      treatment after the age of 50 until the age of 60-65 years is cost-effective at a
      similar level of 10-year major fracture probability (regardless of treatment
      duration). After the age of 65, there is a clear decline in the profitability of
      the therapy. The results indicate that, for the population of women aged >50
      years, the treatment is cost-effective when the 10-year major fracture
      probability equals 5.1% and 6% for a 3- and 5-year therapy, respectively.
      CONCLUSIONS: 1. The study showed pharmacological treatment to be cost-effective
      in a large group of patients forming the study population. 2. The analysis also
      revealed a strong correlation between study results and the specific tool
      employed to define fracture probability.

PMID- 25759157
TI  - Hallux checkrein deformity resulting from the scarring of long flexor muscle
      belly - case report.
AB  - A case of posttraumatic checkrein deformity of the hallux is presented. This
      deformity is most often caused by scarring of the muscle belly or tethering of
      the tendon. A 22-year old woman developed a hallux checkrein deformity after a
      bimaleolar fracture. Intraoperatively, a linear scar tethering the muscle belly
      to the posterior tibia was observed. Resection of the scar allowed for full
      flexor hallucis longus mobility. Full hallux range of motion as well as foot
      function was restored. The cause of the checkrein deformity in our patient was a
      scar tethering the flexor hallucis belly to the posterior tibia. 

PMID- 25759158
TI  - Orthopaedics in Germany under the influence of National-Socialist healt-politic
      in the years 1933-1945.
AB  - In the paper the health-care of physically disabled patients in Germany before,
      during and after the II world war are discussed. The circumstances of
      introduction of "Racial-Hygiene" - laws and orthopedic indications for the
      sterilization and euthanasia are described. Patients with severe physical and
      mental disabilities were potential candidates for annihilation. The tragic fate
      of jewish physicians is remembered. The activity of board of the German
      Orthopeadic Society (DOG) in the years 1933-1945 is described and critically
      analysed.

PMID- 25759159
TI  - [Immobilization and skeletal system of the human body].
AB  - Shaping the process of evolution musculoskeletal and nervous systems in animals
      has allowed these organisms steady increase mobility and mastery of new
      environments to life. Movement is the essence of life and health. But health is
      not a permanent condition. Its absence often results in limited mobility of the
      body. The aim of this study is to assess the impact of immobilization on the
      state of the skeletal system and the evaluation of the effectiveness of various
      measures to reduce this impact. 

PMID- 25759160
TI  - [Is the use of STABHATM for supplementation of damaged extracellular matrix of
      soft tissues in the musculoskeletal system an effective treatment of acute
      injuries and tendinopathies?].
AB  - Viscosupplementation, or the intra articular administration of hyaluronic acid in
      order to stabilise synovial fluid chemistry and improve its functional quality,
      is now a popular therapeutic method whose efficacy, based on numerous published
      studies, makes it not only a form of symptomatic treatment, but also, to a
      considerable extent, a cause-oriented treatment. However, a possibly
      controversial aspect of this therapy is the use of "intra articular hyaluronate"
      in the treatment of post-traumatic or inflammatory soft-tissue lesions in in the
      musculoskeletal system. Inappropriate administration of this dosage form to the
      area of the injured soft tissue (Achilles tendon, periarticular tendon of tarsal
      joint or knee, tennis elbow, tendinopathy within the rotator cuff, etc.) may not
      only lead to a failure to achieve the desired therapeutic effect but can even
      increase the severity of the symptoms, including a rupture of the frayed tendon.
      The role and importance of hyaluronate in the process of natural regeneration of
      damaged soft tissue has been demonstrated unequivocally and beyond any doubt.
      Subsequent research aimed to produce forms of hyaluronic acid that would be
      characterised by a greater influence and support of the regeneration processes in
      musculoskeletal soft tissue after an acute or chronic injury, as well as to
      develop the technology to produce a formulation which would be biocompatible,
      efficient and adapted to the treatment of ligament and tendon injuries. Following
      administration, such formulation would also need to be identified by the body as
      a naturally produced hyaluronate, which plays an essential role in the repair of
      damaged tissue, beginning with the bleeding phase and involving in all phases of
      the healing process, as has been demonstrated in numerous scientific studies. The
      development of a technology for producing hyaluronic acid known as STABHATM (Soft
      Tissue Adapted Biocompatible Hyaluronic Acid) in 2008 proved to be a significant
      achievement in this area. The therapeutic efficacy of STABHATM-containing
      preparations has been documented in many clinical trials with patients treated
      for common musculoskeletal disorders and injuries, such as talocrural sprain, so
      called tennis elbow or rotator cuff tendinopathy. This paper, based on the
      available literature and the authors' clinical experience, reviews the
      therapeutic efficacy of preparations containing STABHATM used in the treatment of
      acute and chronic musculoskeletal soft-tissue injuries to enable the reader to
      make decisions regarding the use of this form of treatment in clinical practice.

PMID- 25759161
TI  - Immobilization of Aspergillus niger lipase on chitosan-coated magnetic
      nanoparticles using two covalent-binding methods.
AB  - Aspergillus niger lipase immobilization by covalent binding on chitosan-coated
      magnetic nanoparticles (CMNP), obtained by one-step co-precipitation, was
      studied. Hydroxyl and amino groups of support were activated using glycidol and
      glutaraldehyde, respectively. Fourier transform infrared spectrometry, high
      resolution transmission electron microscopy and thermogravimetric analysis
      confirmed reaction of these coupling agents with the enzyme and achievement of a
      successful immobilization. The derivatives showed activities of 309.5 +/- 2.0 and
      266.2 +/- 2.8 U (g support)(-1) for the CMNP treated with glutaraldehyde and with
      glycidol, respectively. Immobilization enhanced the enzyme stability against
      changes of pH and temperature, compared to free lipase. Furthermore, the kinetic
      parameters K m and V max were determined for the free and immobilized enzyme. K m
      value quantified for enzyme immobilized by means of glutaraldehyde was 1.7 times
      lowers than for free lipase. High storage stability during 50 days was observed
      in the immobilized derivatives. Finally, immobilized derivatives retained above
      80% of their initial activity after 15 hydrolytic cycles. The immobilized enzyme
      can be applied in various biotechnological processes involving magnetic
      separation.

PMID- 25759162
TI  - Desulfurization and denitrogenation of heavy gas oil by Rhodococcus erythropolis
      ATCC 4277.
AB  - Some of the noxious atmospheric pollutants such as nitrogen and sulfur dioxides
      come from the fossil fuel combustion. Biodesulfurization and biodenitrogenation
      are processes which remove those pollutants through the action of microorganisms.
      The ability of sulfur and nitrogen removal by the strain Rhodococcus erythropolis
      ATCC 4277 was tested in a biphasic system containing different heavy gas oil
      concentrations in a batch reactor. Heavy gas oil is an important fraction of
      petroleum, because after passing through, the vacuum distillation is incorporated
      into diesel oil. This strain was able to remove about 40% of the nitrogen and
      sulfur present in the gas heavy oil. Additionally, no growth inhibition occurred
      even when in the presence of pure heavy gas oil. Results present in this work are
      considered relevant for the development of biocatalytic processes for nitrogen
      and sulfur removal toward building feasible industrial applications.

PMID- 25759164
TI  - Usefulness of MRI-assisted metabolic volumetric parameters provided by
      simultaneous (18)F-fluorocholine PET/MRI for primary prostate cancer
      characterization.
AB  - PURPOSE: The aim of this study was to determine the usefulness of MRI-assisted
      positron emission tomography (PET) parameters provided by simultaneous (18)F
      fluorocholine (FCH) PET/MRI for characterization of primary prostate cancer.
      METHODS: Thirty patients with localized prostate cancer (mean age 69.4 +/- 6.7
      years) confirmed by biopsy were prospectively enrolled for simultaneous PET/MRI
      imaging. The patients underwent (18)F-FCH PET/MRI 1 week before undergoing total
      prostatectomy. Multiple parameters of diffusion-weighted MRI [minimum and mean
      apparent diffusion coefficient (ADCmin and ADCmean)], metabolic PET [maximum and
      mean standardized uptake value (SUVmax and SUVmean)], and metabolic volumetric
      PET [metabolic tumor volume (MTV) and uptake volume product (UVP)] were compared
      with laboratory, pathologic, and immunohistochemical (IHC) features of the
      prostate cancer specimen. PET parameters were divided into two categories as
      follows: volume of interest (VOI) of prostate by SUV cutoff 2.5 (SUVmax, SUVmean,
      MTVSUV, and UVPSUV) and MRI-assisted VOI of prostate cancer (SUVmaxMRI,
      SUVmeanMRI, MTVMRI, and UVPMRI). RESULTS: The rates of prostate cancer-positive
      cases identified by MRI alone, (18)F-FCH PET alone, and (18)F-FCH PET/MRI were
      83.3, 80.0, and 93.3%, respectively. Among the multiple PET/MRI parameters,
      MTVMRI showed fair correlation with serum prostate-specific antigen (PSA; r =
      0.442, p = 0.014) and highest correlation with tumor volume (r = 0.953, p <
      0.001). UVPMRI showed highest correlation with serum PSA (r = 0.531, p = 0.003),
      good correlation with tumor volume (r = 0.908, p < 0.001), and it was
      significantly associated with Gleason score (p = 0.041). High MTVMRI and UVPMRI
      values were significant for perineural invasion, lymphatic invasion,
      extracapsular extension, seminal vesicle invasion, and positive B-cell lymphoma 2
      (Bcl-2) expression (all p < 0.05). CONCLUSION: Simultaneous (18)F-FCH PET/MRI
      demonstrated a better diagnostic value for localized prostate cancer detection
      than each individual modality. MRI-assisted metabolic volumetric PET parameters
      (MTVMRI and UVPMRI) provided more accurate characterization of prostate cancer
      than conventional PET and MRI parameters.

PMID- 25759165
TI  - Tendon and neurovascular injuries of the distal radius after pinning with
      Kirschner wires: A meta-analysis of cadaveric studies.
AB  - Tendon and nerve structures are at risk when displaced fractures of the distal
      radius are pinned using K-wires. The aim of this meta-analysis (MA) is to examine
      the published evidence of such complications in cadavers. Eight studies met our
      inclusion criteria. The meta-analytical results were as follows: (a) 2.87% and
      30.5% tendon involvement at the radial styloid process (RSP) and the dorso-radial
      area of the distal radius, respectively; (b) 3.5% and 1.1% tendon involvement
      when the percutaneous pinning (PP) and the limited open pinning (LOP) techniques
      were used, respectively; (c) 16.1% and 3.4% nerve involvement at the RSP and the
      dorso-radial area of the distal radius, respectively; (d) in 35.7% the nerve was
      speared and in 64.3% it touched the K-wire at the styloid area; (e) 61.3%
      cephalic vein involvement in the styloid area; (f) the second branch of the
      sensitive branch of the radial nerve (SBRN) was the closest to a wire inserted
      into the RSP; (g) the mean (+/-SD) distance between a branch of the SBRN and a
      styloid wire was 2.17 +/- 0.82 mm. Our results for nerve and tendon injury
      frequencies in the RSP were close to those in clinical meta-analytical studies,
      offering an excellent statistical model of evidence synthesis based on cadaveric
      studies to assess the frequency of such injuries in clinical practice. However,
      this cadaveric MA yielded more accurate data than the previously reported
      clinical MA in assessing the real risk of injury of such structures in the distal
      radius in terms of their proximity to the inserted K-wires.

PMID- 25759163
TI  - Establishment and characterization of models of chemotherapy resistance in
      colorectal cancer: Towards a predictive signature of chemoresistance.
AB  - Current standard treatments for metastatic colorectal cancer (CRC) are based on
      combination regimens with one of the two chemotherapeutic drugs, irinotecan or
      oxaliplatin. However, drug resistance frequently limits the clinical efficacy of
      these therapies. In order to gain new insights into mechanisms associated with
      chemoresistance, and departing from three distinct CRC cell models, we generated
      a panel of human colorectal cancer cell lines with acquired resistance to either
      oxaliplatin or irinotecan. We characterized the resistant cell line variants with
      regards to their drug resistance profile and transcriptome, and matched our
      results with datasets generated from relevant clinical material to derive
      putative resistance biomarkers. We found that the chemoresistant cell line
      variants had distinctive irinotecan- or oxaliplatin-specific resistance profiles,
      with non-reciprocal cross-resistance. Furthermore, we could identify several new,
      as well as some previously described, drug resistance-associated genes for each
      resistant cell line variant. Each chemoresistant cell line variant acquired a
      unique set of changes that may represent distinct functional subtypes of
      chemotherapy resistance. In addition, and given the potential implications for
      selection of subsequent treatment, we also performed an exploratory analysis, in
      relevant patient cohorts, of the predictive value of each of the specific genes
      identified in our cellular models. 

PMID- 25759166
TI  - Cerebral perfusion and cortical thickness indicate cortical involvement in mild
      Parkinson's disease.
AB  - Cortical dysfunction in Parkinson's disease (PD) may be caused by disruption to
      ascending systems or by intrinsic cortical neuropathology. We introduce and
      conduct a joint analysis of metabolism and atrophy capable of identifying whether
      metabolic disruption occurs in mild PD without cortical atrophy, to determine the
      extent and spatial pattern of cortical involvement in mild PD. The design was
      observational, studying 23 cognitively normal participants with mild PD (mean
      Hoehn & Yahr stage 2) and 21 healthy controls. Cortical thickness (obtained from
      analysis of structural magnetic resonance imaging [MRI] with FreeSurfer) and
      cerebral perfusion measures (obtained from arterial spin labeling [ASL]) analyzed
      independently and then together in a joint multiple factorial analysis to
      identify spatial patterns of perfusion and cortical thickness. We identify a
      pattern of changes in perfusion and cortical thickness characterized by symmetric
      parietal cortical thinning and reduced precuneus perfusion, with relative
      preservation of thickness and perfusion in the anterior cingulate cortex (ACC),
      right prefrontal gyrus, and medial frontal gyrus. The expression of this pattern
      is correlated with motor system symptoms and speed of processing. A spatial
      pattern of joint parietal cortical thinning and disproportionate reduction in
      perfusion occurs in our nondemented PD sample. We found no PD-related components
      of reduced perfusion without cortical thinning. This suggests that PD affects the
      cortex itself, even when symptoms are relatively mild.

PMID- 25759168
TI  - A higher level of education amplifies the inverse association between income and
      disability in the Spanish elderly.
AB  - BACKGROUND AND AIMS: This paper aims to estimate if the education level modifies
      the association of income with disability prevalence in the elderly. Education
      can have a confounding effect on income or interact with it as a health
      determinant. It is important to analyze the relationship between socio-economic
      status and disability in older people, because it helps to better understand
      health inequalities and organize appropriate social policies. METHODS: The study
      is based on the Survey on Disability, Personal Autonomy and Dependency Situations
      (Spanish National Statistics Institute). Binary logistic regression models are
      adjusted (bivariate, adjusted for gender and age, with all variables and with the
      interaction between income and education levels). A bad adjustment of the model
      is detected and a scobit link is added, which helps to differentiate disabled and
      non-disabled individuals better. RESULTS: People with difficulty in carrying out
      activities of daily living are much older, frequently women and with low
      education and income levels. The significant interaction between education level
      and income means that the odds of being disabled is 43% less in people of high
      income compared with people of low income if they are well educated, while it is
      only 21%, among those with low education. CONCLUSION: A higher education level
      amplifies significantly the inverse association between income and disability in
      the Spanish elderly, what suggests that those with higher education will profit
      more than those with lower education from universal economic benefits policies
      aimed at the disabled, increasing health inequalities between groups.

PMID- 25759170
TI  - Neglected Pipkin's fracture dislocation with bilateral femoral shaft fractures:
      an unusual combination.
AB  - A hip fracture dislocation with contralateral femur fracture is a rare
      combination. We report a case of neglected posterior dislocation of hip with
      Pipkins-II femoral head and medial condylar fractures associated with a
      contralateral femoral shaft fracture. Right hip joint was approached via the
      Kocher-Langenbeck, following reduction, femoral head fragments were fixed with
      two 4-mm cannulated cancellous screws with open reduction internal fixation
      plating of ipsilateral femoral condylar fracture and closed reduction internal
      fixation nailing of left femur in the same sitting. Immediate postoperative X
      rays were satisfactory. Postoperative period was uneventful. Over 7-year follow
      up, patient is successfully performing his duties with X-rays bearing no signs of
      avascular necrosis (AVN) or hip arthritis. Thus, complex femoral fractures
      require a multidisciplinary approach for successful treatment. Early congruous
      reduction, anatomical fixation and early rehabilitation help in reducing the
      incidence of AVN and postoperative arthritis. Successful diagnosis of Pipkin's
      fracture dislocations requires use of CT, MRI and ultrasound in adjunct to X
      rays. 

PMID- 25759171
TI  - A case of abdominal apoplexy because of the rupture of the short gastric vessel.
AB  - Abdominal apoplexy or idiopathic spontaneous intraperitoneal haemorrhage is
      defined as the presence of free blood within the peritoneal cavity. Non-traumatic
      and non-iatrogenic causes may cause abdominal apoplexy. It has a variable
      clinical presentation, with abdominal pain being an early and non-specific
      symptom. We report a rare case of a 23-year-old male with abdominal apoplexy
      because of rupture of the short gastric artery. He presented to our department
      with abdominal pain. Later, he developed signs of shock, and was found to have
      haemoperitoneum on laparotomy. We ligated the short gastric artery, which was the
      bleeding source, and he had an uneventful postoperative course. We also review
      the literature on existing cases of short gastric vessel rupture. 

PMID- 25759169
TI  - The purification and characterization of ATP synthase complexes from the
      mitochondria of four fungal species.
AB  - The ATP synthases have been isolated by affinity chromatography from the
      mitochondria of the fungal species Yarrowia lipolytica, Pichia pastoris, Pichia
      angusta and Saccharomyces cerevisiae. The subunit compositions of the purified
      enzyme complexes depended on the detergent used to solubilize and purify the
      complex, and the presence or absence of exogenous phospholipids. All four enzymes
      purified in the presence of n-dodecyl-beta-D-maltoside had a complete complement
      of core subunits involved directly in the synthesis of ATP, but they were
      deficient to different extents in their supernumerary membrane subunits. In
      contrast, the enzymes from P. angusta and S. cerevisiae purified in the presence
      of n-decyl-beta-maltose neopentyl glycol and the phospholipids 1-palmitoyl-2
      oleoyl-sn-glycero-3-phosphocholine, 1-palmitoyl-2-oleoyl-sn-glycero-3
      phosphoethanolamine, cardiolipin (diphosphatidylglycerol) and 1-palmitoyl-2
      oleoyl-sn-glycero-3-[phospho-rac-(1-glycerol)] had a complete complement of core
      subunits and also contained all of the known supernumerary membrane subunits, e,
      f, g, j, k and ATP8 (or Aap1), plus an additional new membrane component named
      subunit l, related in sequence to subunit k. The catalytic domain of the enzyme
      from P. angusta was more resistant to thermal denaturation than the enzyme from
      S. cerevisiae, but less stable than the catalytic domain of the bovine enzyme,
      but the stator and the integrity of the transmembrane proton pathway were most
      stable in the enzyme from P. angusta. The P. angusta enzyme provides a suitable
      source of enzyme for studying the structure of the membrane domain and properties
      associated with that sector of the enzyme complex.

PMID- 25759172
TI  - Leiomyosarcoma of the ischiorectal fossa: report of a novel sphincter and sciatic
      nerve sparing simultaneous trans-abdominal and trans-gluteal resection and review
      of the literature.
AB  - Leiomyosarcomas are rare tumours of smooth muscle origin, and there have been no
      reported cases of such tumours arising within the ischiorectal fossa. Surgical
      resection with clear margins remains the gold standard treatment; however, there
      is limited literature on surgical approaches to the ischiorectal fossa for such
      tumours. We report a case of a high-grade leiomyosarcoma in a 59-year-old lady,
      occurring within the ischiorectal fossa that was managed using a novel
      simultaneous sphincter and sciatic nerve preserving trans-abdominal and trans
      gluteal technique. This novel approach could be utilized not only for sarcomas
      but also for other tumours of the ischiorectal fossa extending into the gluteal
      region. 

PMID- 25759173
TI  - High prevalence of hyposalivation in individuals with neurofibromatosis 1: a case
      control study.
AB  - BACKGROUND: Neurofibromatosis type 1 (NF1) is one of the most common genetic
      diseases in humans and has widely variable expressivity. Oral manifestations are
      common, but there are no studies that investigated functional alterations in
      salivary glands in NF1. Our aim was to evaluate the salivary flow rate in NF1
      individuals, comparing to a control group, and to investigate the possible causes
      and some consequences of salivary gland alteration. METHODS: This is a case
      control study that evaluated the salivary flow rate of NF1 individuals (n = 49)
      and compared to an age and sex-matched control group. We have also investigated
      the possible causes and consequences of hyposalivation in NF1 individuals through
      anamnesis, a specific questionnaire, physical examination, tongue coating
      evaluation and cytopathological exam to assess the prevalence of oral
      candidiasis. RESULTS: Hyposalivation at rest was present in 59% (29/49) of NF1
      individuals in contrast to 22% (11/49) in the control group, being statistically
      significant (P <0.0001; Wilcoxon rank-sum test). The analysis of the adjusted
      residual showed that the prevalence of hyposalivation in NF1 individuals (46.9%)
      was 4-fold higher than in controls (10.2%). None of the possible causes of
      hyposalivation (medications, low liquid intake, caffeinated or stimulant drink
      use, mouth breathers, alcohol, smoke and plexiform neurofibroma close to or
      involving major salivary glands areas) had important impact on the salivary flow
      rate in NF1 individuals. CONCLUSIONS: Hyposalivation may be a consequence of NF1,
      as occurs in other genetic diseases. More studies are necessary to understand if
      there is and what is the relationship between NF1 and hyposalivation.

PMID- 25759174
TI  - Primary Gross Tumor Volume is an Important Prognostic Factor in Locally Advanced
      Esophageal Cancer Patients Treated with Trimodality Therapy.
AB  - PURPOSE: This study investigated the relationship between tumor volume and
      outcomes in patients receiving trimodality therapy for locally advanced
      esophageal cancer. METHODS: Between 2001 and 2012, 67 patients treated for
      esophageal cancer with chemoradiotherapy followed by esophagectomy who had
      available gross tumor volume (GTV) information were analyzed (35 node-negative,
      32 node-positive patients with primary and nodal GTV contoured as separate
      regions of interest). All gross tumor volumes (GTVs) were contoured at the time
      of radiotherapy treatment planning. GTV optimal cutoff values were determined
      with receiver operating characteristic analysis and deemed significant when chi
      (2) analysis demonstrated differences in examined prognostic variables. Overall
      survival (OS) and progression-free survival (PFS) were analyzed using the Cox
      proportional hazards model. RESULTS: GTVprimary (P = 0.034) and N stage were
      significant multivariate predictors for improved local control; GTVprimary was
      the only multivariate predictor of PFS (P = 0.0299) and OS (P = 0.001228) at 5
      years. Univariate predictors of 5-year PFS and OS included GTVprimary, node
      number, and metastatic lymph node ratio. GTVprimary >85 cc was the best predictor
      for local failure (33.3 %; 8.7 % if <=85 cc). GTVprimary >46 cc correlated with
      an increased risk of 5-year distant failure (37.1 %; 6.7 % if <=46 cc).
      CONCLUSIONS: GTVprimary was a significant multivariate predictor for improved
      local control, PFS, and OS. GTVprimary is a more powerful predictor of patient
      outcomes than traditional TNM staging and should be part of the decision-making
      process when determining optimal local and systemic options for patients with
      locally advanced esophageal cancer.

PMID- 25759176
TI  - Ras moves to stay in place.
AB  - Ras is a major intracellular signaling hub. This elevated position comes at a
      precarious cost: a single point mutation can cause aberrant signaling. The
      capacity of Ras for signaling is inextricably linked to its enrichment at the
      plasma membrane (PM). This PM localization is dynamically maintained by three
      essential elements: alteration of membrane affinities via lipidation and membrane
      interaction motifs; trapping on specific membranes coupled with unidirectional
      vesicular transport to the PM; and regulation of diffusion via interaction with a
      solubilization factor. This system constitutes a cycle that primarily corrects
      for the entropic equilibration of Ras to all membranes that dilutes its signaling
      capacity. We illuminate how this reaction-diffusion system maintains an out-of
      equilibrium localization of Ras GTPases and thereby confers signaling
      functionality to the PM. 

PMID- 25759177
TI  - A home-based training programme improves family caregivers' oral care practices
      with stroke survivors: a randomized controlled trial.
AB  - OBJECTIVES: Stroke survivors experience poor oral health when discharged from the
      hospital to the community. The aim of this study was to evaluate the
      effectiveness of a home-based oral care training programme on knowledge,
      attitude, self-efficacy and practice behaviour of family caregivers. METHODS: A
      randomized controlled trial was conducted. The experimental group consisted of 48
      family caregivers who received the home-based oral care training programme, and
      the control group consisted of 46 family caregivers who received routine oral
      care education. The outcomes were measured by the Knowledge of Oral Care,
      Attitude towards Oral Care, Self-Efficacy of Oral Care and Behaviour of Oral Care
      before the training programme, and at one and two months afterwards. The data
      were analysed using mixed model anova to determine differences in the outcomes
      between the two groups. RESULTS: The findings demonstrated that the intervention
      group had more knowledge (t = 8.80, P < 0. 001), greater self-efficacy (t = 3.53,
      P < 0.01) and better oral care behaviour (t = 11.93, P < 0.001) than the control
      group at one and two months, with statistically significant differences in oral
      care knowledge, self-efficacy and behaviour outcome over time. The attitude of
      the intervention group towards oral care practice was generally positive (mean of
      baseline and two month = 12.9 and 14.7), but no significant difference in
      attitude change between the control and intervention groups (t = 1.56, P = 0.12).
      The treatment interaction effect was significant for the family caregivers'
      behaviour of oral care at one and two months of the intervention for both groups.
      CONCLUSION: Our individualized home-based oral care education can achieve
      significant improvements in oral care knowledge and self-efficacy among family
      caregivers of stroke survivors, and it can sufficiently empower them to modify
      their oral care practices in a home-based healthcare environment.

PMID- 25759175
TI  - How to control self-digestion: transcriptional, post-transcriptional, and post
      translational regulation of autophagy.
AB  - Macroautophagy (hereafter autophagy), literally defined as a type of self-eating,
      is a dynamic cellular process in which cytoplasm is sequestered within a unique
      compartment termed the phagophore. Upon completion, the phagophore matures into a
      double-membrane autophagosome that fuses with the lysosome or vacuole, allowing
      degradation of the cargo. Nonselective autophagy is primarily a cytoprotective
      response to various types of stress; however, the process can also be highly
      selective. Autophagy is involved in various aspects of cell physiology, and its
      dysregulation is associated with a range of diseases. The regulation of autophagy
      is complex, and the process must be properly modulated to maintain cellular
      homeostasis. In this review, we focus on the current state of knowledge
      concerning transcriptional, post-transcriptional, and post-translational
      regulation of autophagy in yeast and mammals. 

PMID- 25759178
TI  - Possible harms in sharing patients' clinical notes.

PMID- 25759179
TI  - Extended follow-up of lung cancer and non-malignant respiratory disease mortality
      among California diatomaceous earth workers.
AB  - OBJECTIVES: Millions of workers worldwide are employed in occupations involving
      potentiality hazardous exposure to crystalline silica. The diatomaceous earth
      industry can have particularly high exposures, but there is a lower likelihood of
      simultaneously occurring confounding exposures. We extended follow-up for
      diatomaceous earth industry workers previously studied for mortality. METHODS:
      The cohort included 2342 white men who were employed for at least 1 year at a
      diatomaceous earth plant in Lompoc, California beginning in 1942. Workers' vital
      status was updated using the National Death Index through 2011, an extension of
      19 years from earlier studies. Detailed work history and quantitative air
      monitoring measurements estimated exposure intensity. Cox proportional hazards
      modelling estimated HRs and 95% CIs. SMRs were calculated. RESULTS: Elevated
      mortality was observed by quartile of cumulative crystalline silica exposure for
      lung cancer (HR=2.03, 95% CI 1.07 to 3.85, highest quartile, unlagged) and non
      malignant respiratory disease (NMRD) (HR=3.59, 95% CI 1.94 to 6.67, highest
      quartile, unlagged), although trends were not statistically significant.
      Associations were attenuated when adjusted for smoking and asbestos exposure.
      Mortality from NMRD was significantly increased over the entire follow-up
      compared to the general population (SMR=1.37, 95% CI 1.17 to 1.60). An increase
      for lung cancer was confined to the earlier follow-up (SMR=1.29, 95% CI 1.01 to
      1.61). CONCLUSIONS: The risk of lung cancer and NMRD mortality remained elevated,
      although generally non-significant, and exposure-response trends with cumulative
      crystalline silica persisted on extended follow-up of this cohort. The findings
      support a generally consistently observed aetiological relation between
      crystalline silica and lung cancer.

PMID- 25759180
TI  - Workplace climate, employee actions, work injury and structural equation
      modelling.

PMID- 25759181
TI  - Evaluation of the Dual-Chamber Pen Design for the Injection of Exenatide Once
      Weekly for the Treatment of Type 2 Diabetes.
AB  - BACKGROUND: Exenatide once weekly, an injectable glucagon-like peptide-1 receptor
      agonist, has been shown to reduce A1C, fasting glucose, and body weight in
      patients with type 2 diabetes. Exenatide 2.0 mg is dispersed in poly-(D,L-lactide
      co-glycolide) polymer microspheres, which require resuspension in aqueous diluent
      before subcutaneous injection. A single-use, dual-chamber pen was developed to
      improve the convenience of exenatide once weekly delivery and tested following
      Food and Drug Administration (FDA) guidance. METHODS: Design development goals
      were established, and validation tests (dose accuracy, torque/force requirements,
      usability, and ease-of-use) were performed. Dose accuracy was tested under a
      variety of conditions. After 10 exploratory studies in 329 patients, the final
      design's usability and ease-of-use were tested in untrained health care
      practitioners (HCPs; n = 16) and untrained/trained patients (n = 30/17).
      Usability testing evaluated completion of multiple setup, dose preparation, and
      injection steps. Ease-of-use impression was assessed using a scale of 1-7 (1 =
      very difficult, 7 = very easy). RESULTS: The dual-chamber pen successfully met
      development goals and delivered target volume (650 uL +/- 10%) under tested
      conditions (mean 644.7-649.3 uL), with torque and force requirements below
      prespecified maximum values. In the final user study, most participants (>=87%)
      correctly completed pen setup, dose preparation, and injection steps. Mean ease
      of-use scores were 5.8, 6.3, and 6.5 out of 7 in untrained HCPs, untrained
      patients, and trained patients, respectively. CONCLUSION: With self-education or
      minimal training, participants accurately and precisely suspended, mixed, and
      delivered exenatide-containing microspheres using the dual-chamber pen with high
      ease-of-use scores. The dual-chamber pen was FDA-approved in February 2014.

PMID- 25759182
TI  - Translating What Works: A New Approach to Improve Diabetes Management.
AB  - BACKGROUND: The most efficacious strategies to improve diabetes control include
      case management, health care team changes, patient education, and facilitated
      transmission of patient data to clinicians ("facilitated relay"), but these
      strategies have not been translated to permit general use in clinical practice.
      METHODS: A web-based decision support program was developed to include these
      features, and assessed in patients who had A1c >=7.0% despite using metformin
      with/without sulfonylureas or insulin. Staff entered patients' glucose data,
      obtained management recommendations, reviewed the plan with a clinician, and
      discussed the new plan with patients. RESULTS: 113 subjects were 96% male and 32%
      black, with average age 65.6 years and BMI 32.8. During prior primary care, A1c
      averaged 8.32 +/- 0.16% (SEM). In all patients, baseline A1c was 8.18 +/- 0.11%,
      and decreased to 7.54 +/- 0.12%, 7.16 +/- 0.13%, and 7.54 +/- 0.16% at 3, 6, and
      12 months, respectively, all P < .001. In 42 subjects who provided glucose data
      and made requested changes in medications, A1c was 8.12 +/- 0.09% at baseline and
      fell to 7.29 +/- 0.11%, 6.98 +/- 0.10%, and 7.05 +/- 0.10% at 3, 6, and 12
      months, respectively, all P < .001. Chart review of 16 subjects followed for 12
      months demonstrated that hypoglycemia (symptoms and/or glucose <70 mg/dl)
      averaged less than 1 episode/patient/month, and there was no severe hypoglycemia.
      CONCLUSIONS: A novel decision support program improved A1c with little
      hypoglycemia. Use of this approach should allow primary care teams to keep
      patients well controlled, and reduce the need for specialist referrals.

PMID- 25759184
TI  - Pharmacokinetic Model of the Transport of Fast-Acting Insulin From the
      Subcutaneous and Intradermal Spaces to Blood.
AB  - Pharmacokinetic (PK) models describing the transport of insulin from the
      injection site to blood assist clinical decision making and are part of in silico
      platforms for developing and testing of insulin delivery strategies for treatment
      of patients with diabetes. The ability of these models to accurately describe all
      facets of the in vivo insulin transport is therefore critical for their
      application. Here, we propose a new model of fast-acting insulin analogs
      transport from the subcutaneous and intradermal spaces to blood that can
      accommodate clinically observed biphasic appearance and delayed clearance of
      injected insulin, 2 phenomena that are not captured by existing PK models. To
      develop the model we compare 9 insulin transport PK models which describe
      hypothetical insulin delivery pathways potentially capable of approximating
      biphasic appearance of exogenous insulin. The models are tested with respect to
      their ability to describe clinical data from 10 healthy volunteers which received
      1 subcutaneous and 2 intradermal insulin injections on 3 different occasions. The
      optimal model, selected based on information and posterior identifiability
      criteria, assumes that insulin is delivered at the administrative site and is
      then transported to the bloodstream via 2 independent routes (1) diffusion-like
      process to the blood and (2) combination of diffusion-like processes followed by
      an additional compartment before entering the blood. This optimal model accounts
      for biphasic appearance and delayed clearance of exogenous insulin. It agrees
      better with the clinical data as compared to commonly used models and is expected
      to improve the in silico development and testing of insulin treatment strategies,
      including artificial pancreas systems. 

PMID- 25759185
TI  - Amplitude Modulation Mode of Scanning Ion Conductance Microscopy.
AB  - Live-cell imaging at the nanoscale resolution is a hot research topic in the
      field of life sciences for the direct observation of cellular biological
      activity. Scanning ion conductance microscopy (SICM) is one of the few effective
      imaging tools for live-cell imaging at the nanoscale resolution. However, there
      are various problems in existing scanning modes. The hopping and AC modes suffer
      from low speed, whereas the DC mode is prone to instability because of the DC
      drift and external electrical interference. In this article, we propose an
      amplitude modulation (AM) mode of SICM, which employs an AC voltage to enhance
      the stability and improve the scanning speed. In this AM mode, we introduce a
      capacitance compensation method to eliminate capacitance effect and use the
      amplitude of the AC current component to control the tip movement. Experimental
      results on polydimethylsiloxane samples verify the validity of the AM mode and
      demonstrate an improved performance of both speed and stability of this new mode.

PMID- 25759183
TI  - HypoDE: Research Design and Methods of a Randomized Controlled Study Evaluating
      the Impact of Real-Time CGM Usage on the Frequency of CGM Glucose Values <55
      mg/dl in Patients With Type 1 Diabetes and Problematic Hypoglycemia Treated With
      Multiple Daily Injections.
AB  - Systems for continuous glucose monitoring (CGM) have been available for a number
      of years, and numerous clinical studies have been performed with them.
      Interestingly, in many of these studies patients with an increased risk of
      hypoglycemic events were excluded. In addition, in most studies subjects were
      using a pump for insulin delivery. Therefore our knowledge about the benefit of
      CGM in patients employing multiple daily injections (MDI) of insulin is limited,
      especially when it comes to a reduction in the risk of low glucose events in high
      risk individuals. We are planning to run a 26-week randomized controlled study in
      Germany (HypoDE, Hypoglycemia in Deutschland) that is focused on evaluating if
      such a reduction can be observed in patients on MDI with an increased risk of low
      glucose events. In all, 160 patients will participate in the study, randomized
      into the intervention group and control group. Ideally one would study if the
      frequency of severe hypoglycemic events is different between both groups.
      However, this would require such a large sample size and study duration, so for
      pragmatic reasons we will use low glucose levels <55 mg/dl (measured by CGM) for
      at least 20 minutes as a risk marker for severe hypoglycemic events. The results
      from the HypoDE study shall help determine the advantage of using CGM in subjects
      with type 1 diabetes with an increased risk of low glucose events treated with
      MDI. 

PMID- 25759186
TI  - Interrelationship Between Alcohol Intake and Endogenous Sex-Steroid Hormones on
      Diabetes Risk in Postmenopausal Women.
AB  - OBJECTIVE: We examined whether circulating concentrations of sex hormones,
      including estradiol, testosterone, sex hormone-binding globulin (SHBG), and
      dehydroepiandrosterone sulfate (DHEAS), were associated with alcohol intake or
      mediated the alcohol-type 2 diabetes (T2D) association. METHODS: Among women not
      using hormone replacement therapy and free of baseline cardiovascular disease,
      cancer, and diabetes in the Women's Health Study, 359 incident cases of T2D and
      359 matched controls were chosen during 10 years of follow-up. RESULTS: Frequent
      alcohol intake (>=1 drink/day) was positively and significantly associated with
      higher plasma estradiol concentrations in an age-adjusted model (beta = 0.14, 95%
      confidence interval [CI], 0.03, 0.26), compared to rarely/never alcohol intake.
      After adjusting for additional known covariates, this alcohol-estradiol
      association remained significant (beta = 0.19, 95% CI, 0.07, 0.30). Testosterone
      (beta = 0.13, 95% CI, -0.05, 0.31), SHBG (beta = 0.07, 95% CI, -0.07, 0.20), and
      DHEAS (beta = 0.14, 95% CI, -0.04, 0.31) showed positive associations without
      statistical significance. Estradiol alone or in combination with SHBG appeared to
      influence the observed protective association between frequent alcohol
      consumption and T2D risk, with a 12%-21% reduction in odds ratio in the
      multivariate-adjusted models. CONCLUSIONS: Our cross-sectional analysis showed
      positive associations between alcohol intake and endogenous estradiol
      concentrations. Our prospective data suggested that baseline concentrations of
      estradiol, with or without SHBG, might influence the alcohol-T2D association in
      postmenopausal women.

PMID- 25759187
TI  - Current ADC Linker Chemistry.
AB  - The list of ADCs in the clinic continues to grow, bolstered by the success of
      first two marketed ADCs: ADCETRIS(r) and Kadcyla(r). Currently, there are 40 ADCs
      in various phases of clinical development. However, only 34 of these have
      published their structures. Of the 34 disclosed structures, 24 of them use a
      linkage to the thiol of cysteines on the monoclonal antibody. The remaining 10
      candidates utilize chemistry to surface lysines of the antibody. Due to the
      inherent heterogeneity of conjugation to the multiple lysines or cysteines found
      in mAbs, significant research efforts are now being directed toward the
      production of discrete, homogeneous ADC products, via site-specific conjugation.
      These site-specific conjugations may involve genetic engineering of the mAb to
      introduce discrete, available cysteines or non-natural amino acids with an
      orthogonally-reactive functional group handle such as an aldehyde, ketone, azido,
      or alkynyl tag. These site-specific approaches not only increase the homogeneity
      of ADCs but also enable novel bio-orthogonal chemistries that utilize reactive
      moieties other than thiol or amine. This broadens the diversity of linkers that
      can be utilized which will lead to better linker design in future generations of
      ADCs. 

PMID- 25759188
TI  - Chest-Wall Metastasis of Prostate Cancer.

PMID- 25759189
TI  - Determination of Injury Risks and Safety Measures Taken by Mothers of Children
      With an Intellectual Disability and Autism Spectrum Disorder.
AB  - PURPOSE: The purpose of the study is to determine the injury risk behaviors and
      home safety measures in children with an intellectual disability or autism
      spectrum disorder. METHOD: The study sample included mothers of 100 children
      between the ages of 2 and 12 years. FINDINGS: There was a significant difference
      between the home safety measures and the children's ages, the birth order of the
      children, and the mother's and father's ages. There was not a significant
      relationship between the children's ages, diagnosis, and Injury Behavior
      Checklist (IBC). There is a positive correlation between the total score of the
      Home Safety Measures Control List and IBC.

PMID- 25759191
TI  - Monolithic DSSC/CIGS tandem solar cell fabricated by a solution process.
AB  - Tandem architecture between organic (dye-sensitized solar cell, DSSC) and
      inorganic (CuInGaSe2 thin film solar cell, CIGS) single-junction solar cells was
      constructed particularly based on a solution process. Arc-plasma deposition was
      employed for the Pt interfacial layer to minimize the damage to the layers of the
      CIGS bottom cell. Solar cell efficiency of 13% was achieved, which is significant
      progress from individual single-junction solar cells (e.g., 7.25 and 6.2% for
      DSSC and CIGS, respectively). 

PMID- 25759193
TI  - Population data of mitochondrial DNA HVS-I and HVS-II sequences for 208 Henan Han
      Chinese.
AB  - The two hypervariable segments (HVS-I and HVS-II) of mitochondrial DNA (mtDNA)
      control region were sequenced for a population of 208 unrelated healthy
      individuals sampled from Suiping County, Henan Province, China. A total of 192
      different haplotypes were identified, of which 179 haplotypes were unique
      (93.23%). The variation of the mtDNA HVS-I and HVS-II was confined to 166
      nucleotide positions, of which 115 were observed in the HVS-I and 51 in the HVS
      II. The haplotype diversity and random match probability were 0.9991 and 0.0061,
      respectively. Following the principle of the updated East Asian mtDNA phylogeny
      tree, individual samples were assigned to the specific haplogroups based on the
      information both from control region and coding-region obtained. Haplogroup D was
      the most common haplogroup (25.96%). The northern China-prevalent haplogroups (A,
      C, D, G, M8, Y, and Z) and the southern China-prevalent haplogroups (B, F, M7,
      N9, and R9) accounted for 48.56% and 46.63%, respectively, of the Henan Han mtDNA
      gene pool. The mtDNA hypervariable region was highly polymorphic in Henan Han
      population. These sequences could serve as mtDNA reference data for forensic
      casework in Henan population as well as for population genetic study. 

PMID- 25759192
TI  - Ancestry informative markers for distinguishing between Thai populations based on
      genome-wide association datasets.
AB  - The main purpose of this work was to identify a set of AIMs that stratify the
      genetic structure and diversity of the Thai population from a high-throughput
      autosomal genome-wide association study. In this study, more than one million
      SNPs from the international HapMap database and the Thai depression genome-wide
      association study have been examined to identify ancestry informative markers
      (AIMs) that distinguish between Thai populations. An efficient strategy is
      proposed to identify and characterize such SNPs and to test high-resolution SNP
      data from international HapMap populations. The best AIMs are identified to
      stratify the population and to infer genetic ancestry structure. A total of 124
      AIMs were clearly clustered geographically across the continent, whereas only 89
      AIMs stratified the Thai population from East Asian populations. Finally, a set
      of 273 AIMs was able to distinguish northern from southern Thai subpopulations.
      These markers will be of particular value in identifying the ethnic origins in
      regions where matching by self-reports is unavailable or unreliable, which
      usually occurs in real forensic cases. 

PMID- 25759194
TI  - Platinum-catalyzed domino reaction with benziodoxole reagents for accessing
      benzene-alkynylated indoles.
AB  - Indoles are omnipresent in natural products, bioactive molecules, and organic
      materials. Consequently, their synthesis or functionalization are important
      fields of research in organic chemistry. Most works focus on installation or
      modification of the pyrrole ring. To access benzene-ring-functionalized indoles
      with an unsubstituted pyrrole ring remains more challenging. Reported herein is a
      platinum-catalyzed cyclization/alkynylation domino process to selectively obtain
      C5- or C6-functionalized indoles starting from easily available pyrroles. The
      work combines, for the first time, a platinum catalyst with ethynylbenziodoxole
      hypervalent iodine reagents in a domino process for the synthesis of
      polyfunctionalized arene rings and gives access to important building blocks for
      the synthesis of bioactive compounds and organic materials. 

PMID- 25759195
TI  - Scholarly elves?

PMID- 25759196
TI  - Objective sleep of older primiparous Japanese women during the first 4 months
      postpartum: an actigraphic study.
AB  - This longitudinal study was designed to examine objective sleep parameters of
      older primiparous Japanese women during the first 4 months postpartum using
      actigraphy. The participants were 18 older primiparae (Mean (SD) = 37.06 (2.62)
      years, range 35-44 years) who gave birth to healthy neonates at one of three
      urban Japanese hospitals. Objective sleep quality was measured using actigraphy
      for 48 h at 1, 2 and 4 months postpartum. The Friedman test was used to test for
      differences in sleep parameters across time. Sleep duration (SMIN) increased
      significantly from 2 months (Mean (M) = 301.94 min) to 4 months (M = 372.78 min).
      Sleep efficiency (SE) increased significantly from 1 month (73.52%) to 2 (86.66%)
      and 4 months (89.05%). Waking after sleep onset (WASO) decreased significantly
      from 1 month (M = 114.64 min) to 2 (M = 40.18 min) and 4 months (M = 38.36 min)
      and long waking episodes (LWEP) significantly decreased from 1 month (4.67) to 2
      (2.69) and 4 months (3.12). Persistent postpartum sleep problems can be a sign of
      postpartum depression as well as health problems among infants. 

PMID- 25759197
TI  - Comparing older and younger Japanese primiparae: fatigue, depression and
      biomarkers of stress.
AB  - This cohort study of primiparae was conducted to answer the following questions:
      Do older (? 35 years) and younger (20-29 years) Japanese primiparous mothers
      differ when comparing biomarkers of stress and measures of fatigue and
      depression? Are there changes in fatigue, depression and stress biomarkers when
      comparing older and younger mothers during the postpartum period? The Postnatal
      Accumulated Fatigue Scale and the Edinburgh Postnatal Depression Scale were
      administered in a time-series method four times: shortly after birth and monthly
      afterwards. Assays to measure biomarkers of stress, urinary 17-ketosteroids,
      urinary 17-hydroxycorticosteroids and salivary chromogranin-A, were collected
      shortly after delivery and at 1 month postpartum in both groups and a third time
      in older mothers at the 4th month. Statistical testing showed very little
      difference in fatigue, depression or stress biomarkers between older and younger
      mothers shortly after birth or 1 month later. Accumulated fatigue and depression
      scores of older mothers were highest 1 month after delivery. Additional cohort
      studies are required to characterize physical/psychological well-being of older
      Japanese primiparae. 

PMID- 25759198
TI  - Clinical competency in child maltreatment for community nurses in Taiwan.
AB  - The purpose of this cross-sectional study was to examine aspects of competency in
      child abuse among community nurses in Taiwan. A sample of 650 community nurses
      were recruited from public health centres (PHC) and outpatient clinics in
      Southern Taiwan. A structured questionnaire with five subscales, knowledge,
      skills, empowerment, team collaboration and self-reflection was developed and
      used for data collection. A total of 588 questionnaires were returned and used
      for analysis. Nearly 20% of community nurses reported having an acquaintance with
      a maltreatment history. Only 4.6% had experience of reporting a case of child
      abuse. Most nurses reported strong skills and abilities (empowerment, team
      collaboration and self-reflection). Outpatient clinic nurses scored higher in
      four subscales than the PHC nurses. Nurses who had a history as a victim or had
      reporting experience claimed better clinical competency. Unfortunately, community
      nurses had limited knowledge in child abuse. The findings support the development
      of continuing education programmes on child abuse for community nurses. 

PMID- 25759199
TI  - Caring for women globally: psychometric testing of two instruments translated
      into five languages for use in cardiovascular recovery.
AB  - Among women, cardiovascular disease is the leading cause of mortality worldwide.
      After experiencing an acute cardiovascular event, a woman's physical health, the
      prevalence of morbidities, likelihood of being treated with coronary artery
      bypass graft surgery, likelihood for referral for cardiac rehabilitation are less
      favourable than men. The social support resources of marginality and
      religiousness are associated with physical and mental health outcomes following
      cardiovascular crises. This study aimed to evaluate the reliability and validity
      of the translated versions (Japanese, Ukrainian, Tagalog, Hispanic and Arabic) of
      the Koci Marginality Index and the Duke University Religion Index among 282 women
      (aged 35-92 years) representing seven cultures. Results showed that reliability
      and validity were strong (coefficient alpha of 0.79 and 0.84). Understanding a
      woman's social isolation and whether she has a connection to religious groups
      assists health-care professionals to identify a woman's social support resources
      during recovery following acute cardiovascular episodes. 

PMID- 25759200
TI  - Strengths and capabilities of Chinese patients with severe ocular injuries: a
      qualitative study.
AB  - The purpose of this qualitative study is to illustrate health-centred nursing by
      assessing the capabilities of patients with acute and severe ocular injuries.
      This study draws upon analyzing 17 nursing encounters with four adult male
      patients admitted to the ophthalmological ward of a university hospital in a
      rural Chinese city. The analysis identified that patients demonstrated the
      following strengths: (i) comprehension; (ii) self-reflection and examination;
      (iii) cooperation; (iv) patience and self-control; (v) self-efficacy; (vi)
      proactive acceptance; (vii) independence and a positive attitude towards
      challenges; (viii) support from family members; (ix) volition; and (x)
      flexibility. The results of this study highlight the importance of observing
      patients, assessing their abilities and helping them mobilize these strengths for
      recovery. 

PMID- 25759201
TI  - Providing cultural care behind the spotlight at the Olympic Games.
AB  - The Olympic Games constitutes the world's largest sporting event. Nurses play an
      important, but poorly discussed, role in emergency care, routine clinical care
      and preventive care for athletes from many cultures as well as an enormous influx
      of spectators. In this article, we discuss five important considerations when
      preparing nurses to provide safe care for Olympians: elite athletes as a cultural
      group; caring for the Olympic family; disaster preparedness and security;
      infection control; and principles of transcultural nursing. Because of the nature
      of the sports and types of injuries and the effects of climate, these challenges
      differ somewhat between the summer and winter Olympics. Nevertheless, the Olympic
      games provide a tremendous opportunity to experience transcultural nursing and to
      highlight how nurses play a significant role in the care of the athletes, the
      Olympic family, and the spectators. 

PMID- 25759202
TI  - Malignant seminoma in two unilaterally cryptorchid stallions.
AB  - Two unilateral cryptorchid stallions were referred to the clinic because of
      chronic debilitating condition with emaciation. Rectal examination, and
      ultrasound and gross examination revealed in both animals an abdominal mass,
      caudally of the kidney, and multiple nodules spread over the abdomen. Histologic
      analysis revealed an intra-abdominal malignant seminoma with intraperitoneal and
      renal metastasis. Interestingly, a seminoma was also present in the descended
      testis of the draught horse. 

PMID- 25759203
TI  - High performance surface-enhanced Raman scattering from molecular imprinting
      polymer capsulated silver spheres.
AB  - Driven by the ultrasensitivity of the surface-enhanced Raman scattering (SERS)
      technique and the directive selection of molecular imprinting polymers (MIPs),
      core-shell silver-molecularly imprinted polymer (Ag@MIP) hybrid structure was
      synthesized to serve as a novel SERS platform. The results show that as prepared
      Ag@MIPs wrapped over a thin shell of MIPs are sensitive to the template molecule
      (Rhodamine 6G). To investigate the selectivity of Ag@MIPs, the structurally
      related molecules, such as Rhodamine B and crystal violet, were chosen as
      controls. Notably, the high sensitivity of Ag@MIPs is restrained by the non
      specific recognition of Rhodamine B and crystal violet. This high SERS
      enhancement of the template molecule can be interpreted by the "gate effect"
      and/or "dummy hot spots". We believe that the sensitivity of SERS coupled with
      the selectivity of MIPs could induce a promising chemosensor or biosensor for
      practical applications. 

PMID- 25759204
TI  - Filtration of ultrafine metallic particles in industry.
AB  - Thermal metal spraying, metal cutting and arc welding processes generate large
      quantities of ultrafine particles that cause the irreversible clogging of
      industrial filters. The aim of the study performed was to identify the causes of
      the clogging of cartridge filters and investigate other paths for cleaning them.
      This study required the development of a test bench capable of reproducing a
      thermal spraying process to test the performances of different filtration
      techniques. This test instrument first, permitted the precise characterization of
      the aerosol generated by the process and, second, defined the clogging and
      cleaning conditions for filters. Several parameters were tested: the type of
      filter, online and off-line cleaning, pre-coating, cleaning by jets of high-speed
      compressed air via a probe. 

PMID- 25759205
TI  - A systemic Pasteurella multocida toxin aggravates cardiac hypertrophy and
      fibrosis in mice.
AB  - Pasteurella multocida toxin (PMT) persistently activates heterotrimeric G
      proteins of the Galphaq/11 , Galpha12/13 and Galphai family without interaction
      with G protein-coupled receptors (GPCRs). We show that PMT acts on heart tissue
      in vivo and on cardiomyocytes and cardiac fibroblasts in vitro by deamidation of
      heterotrimeric G proteins. Increased normalized ventricle weights and fibrosis
      were detected after intraperitoneal administration of PMT in combination with the
      GPCR agonist phenylephrine. In neonatal rat cardiomyocytes, PMT stimulated the
      mitogen-activated protein kinase pathway, which is crucial for the development of
      cellular hypertrophy. The toxin induced phosphorylation of the canonical
      phosphorylation sites of the extracellular-regulated kinase 1/2 and,
      additionally, caused phosphorylation of the recently recognized
      autophosphorylation site, which appears to be important for the development of
      cellular hypertrophy. Moreover, PMT stimulated the small GTPases Rac1 and RhoA.
      Both switch proteins are involved in cardiomyocyte hypertrophy. In addition, PMT
      stimulated RhoA and Rac1 in neonatal rat cardiac fibroblasts. RhoA and Rac1 have
      been implicated in the regulation of connective tissue growth factor (CTGF)
      secretion and expression. Accordingly, we show that PMT treatment increased
      secretion and expression of CTGF in cardiac fibroblasts. Altogether, the data
      indicate that PMT is an inducer of pathological remodelling of cardiac cells and
      identifies the toxin as a promising tool for studying heterotrimeric G protein
      dependent signalling in cardiac cells. 

PMID- 25759206
TI  - Chondroitin sulfate-E mediates estrogen-induced osteoanabolism.
AB  - Osteoporosis is an age-related disorder of bone remodeling in which bone
      resorption outstrips bone matrix deposition. Although anticatabolic agents are
      frequently used as first-line therapies for osteoporosis, alternative anabolic
      strategies that can enhance anabolic, osteogenic potential are actively sought.
      Sex steroid hormones, particularly estrogens, are bidirectional regulators for
      bone homeostasis; therefore, estrogen-mediated events are important potential
      targets for such anabolic therapies. Here, we show that estrogen-induced,
      osteoanabolic effects were mediated via enhanced production of chondroitin
      sulfate-E (CS-E), which could act as an osteogenic stimulant in our cell-based
      system. Conversely, estrogen deficiency caused reduced expression of CS-E
      synthesizing enzymes, including GalNAc4S-6ST, and led to decreased CS-E
      production in cultures of bone marrow cells derived from ovariectomized mice.
      Moreover, Galnac4s6st-deficient mice had abnormally low bone mass that resulted
      from impaired osteoblast differentiation. These results indicated that strategies
      aimed at boosting CS-E biosynthesis are promising alternative therapies for
      osteoporosis. 

PMID- 25759207
TI  - [Acute pancreatitis associated with amoxycillin-clavulanic acid].

PMID- 25759208
TI  - Rank-dependent grooming patterns and cortisol alleviation in Barbary macaques.
AB  - Flexibly adapting social behavior to social and environmental challenges helps to
      alleviate glucocorticoid (GC) levels, which may have positive fitness
      implications for an individual. For primates, the predominant social behavior is
      grooming. Giving grooming to others is particularly efficient in terms of GC
      mitigation. However, grooming is confined by certain limitations such as time
      constraints or restricted access to other group members. For instance, dominance
      hierarchies may impact grooming partner availability in primate societies.
      Consequently specific grooming patterns emerge. In despotic species focusing
      grooming activity on preferred social partners significantly ameliorates GC
      levels in females of all ranks. In this study we investigated grooming patterns
      and GC management in Barbary macaques, a comparably relaxed species. We monitored
      changes in grooming behavior and cortisol (C) for females of different ranks. Our
      results show that the C-amelioration associated with different grooming patterns
      had a gradual connection with dominance hierarchy: while higher-ranking
      individuals showed lowest urinary C measures when they focused their grooming on
      selected partners within their social network, lower-ranking individuals
      expressed lowest C levels when dispersing their grooming activity evenly across
      their social partners. We argue that the relatively relaxed social style of
      Barbary macaque societies allows individuals to flexibly adapt grooming patterns,
      which is associated with rank-specific GC management.

PMID- 25759209
TI  - The risks of risk scores for stroke risk assessment in atrial fibrillation.

PMID- 25759210
TI  - MTBP inhibits migration and metastasis of hepatocellular carcinoma.
AB  - Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide with
      increasing incidence. Despite curative surgical resection and advanced
      chemotherapy, its survival rate remains low. The presence of microvascular
      invasion and occult metastasis is one of the major causes for this poor outcome.
      MDM2 Binding Protein (MTBP) has been implicated in the suppression of cell
      migration and cancer metastasis. However, clinical significance of MTBP,
      particularly in human cancer, is poorly understood. Specifically, clinical
      relevance of MTBP in human HCC has never been investigated. Here we demonstrated
      that expression of MTBP was significantly reduced in human HCC tissues compared
      to adjacent non-tumor tissues. MTBP expression was negatively correlated with
      capsular/vascular invasion and lymph node metastasis. Overexpression of MTBP
      resulted in the suppression of the migratory and metastatic potential of HCC
      cells, while its downregulation increased the migration. Consistent with the
      previous report, MTBP endogenously bound to alpha-actinin 4 (ACTN4) and
      suppressed ACTN4-mediated cell migration in multiple HCC cell lines. However,
      MTBP also inhibited migratory potential of PLC/PRF/5 HCC cells whose migration
      was not altered by manipulation of ACTN4 expression. These results suggest that
      mechanisms behind MTBP-mediated migration suppression may not be limited to the
      pathway involving ACTN4 in certain cellular contexts. Additionally, as a
      potential mechanism for reduced MTBP expression in tumors, we found that MTBP
      expression was increased following the treatment with histone deacetylase
      inhibitors (HDIs). Our study, for the first time, provides clinical relevance of
      MTBP in the suppression of HCC metastasis. 

PMID- 25759213
TI  - A new approach using micro HPLC-MS/MS for multi-mycotoxin analysis in maize
      samples.
AB  - Using micro high-performance liquid chromatography-tandem mass spectrometry (HPLC
      MS/MS) a simple and fast method for the quantitative determination of 26
      mycotoxins was developed. Sample preparation consists of a single extraction step
      and a dilute-and-shoot approach without further cleanup. With a total run time of
      9 min and solvent consumption below 0.3 mL per chromatographic run, the presented
      method is cost-effective. All toxins regulated by the European Commission with
      maximum or guidance levels in grain products (fumonisins B1 and B2 (FB1 and
      FB2)); deoxynivalenol (DON); aflatoxins B1, G1, B2, and G2 (AFB1, AFG1, AFB2, and
      AFG2); ochratoxin A (OTA); T-2 and HT-2 toxins; and zearalenone (ZEN) can be
      quantified with this method. Furthermore, the enniatins B, B1, A, and A1 (EnB,
      EnB1, EnA, and EnA1); beauvericin (BEA); 3-acetyl-deoxynivalenol (3-AcDON);
      fusarin C (FusC); sterigmatocystin (STC); gliotoxin (GT); and the Alternaria
      toxins alternariol (AOH), alternariol monomethyl ether (AME), altenuene (ALT),
      tentoxin (TEN), and altertoxin I (ATX I) can also be quantified. For all
      regulated compounds, recoveries ranged between 76 and 120%. For all other toxins,
      the recovery was at least 51%. The method was applied for the analysis of 42
      maize samples from field trials in South Africa.

PMID- 25759212
TI  - A distinct and replicable variant of the squamous cell carcinoma gene inositol
      polyphosphate-5-phosphatase modifies the susceptibility of arsenic-associated
      skin lesions in Bangladesh.
AB  - BACKGROUND: Single-nucleotide polymorphisms (SNPs) in inflammation, one-carbon
      metabolism, and skin cancer genes might influence susceptibility to arsenic
      induced skin lesions. METHODS: A case-control study was conducted in Pabna,
      Bangladesh (2001-2003), and the drinking-water arsenic concentration was measured
      for each participant. A panel of 25 candidate SNPs was analyzed in 540 cases and
      400 controls. Logistic regression was used to estimate the association between
      each SNP and the potential for gene-environment interactions in the skin lesion
      risk, with adjustments for relevant covariates. Replication testing was conducted
      in an independent Bangladesh population with 488 cases and 2,794 controls.
      RESULTS: In the discovery population, genetic variants in the one-carbon
      metabolism genes phosphatidylethanolamine N-methyltransferase (rs2278952, P for
      interaction  = .004; rs897453, P for interaction = .05) and dihydrofolate
      reductase (rs1650697, P for interaction = .02), the inflammation gene interleukin
      10 (rs3024496, P for interaction =.04), and the skin cancer genes inositol
      polyphosphate-5-phosphatase (INPP5A; rs1133400, P for interaction = .03) and
      xeroderma pigmentosum complementation group C (rs2228000, P for interaction =
      .01) significantly modified the association between arsenic and skin lesions
      after adjustments for multiple comparisons. The significant gene-environment
      interaction between a SNP in the INPP5A gene (rs1133400) and water arsenic with
      respect to the skin lesion risk was successfully replicated in an independent
      population (P for interaction = .03). CONCLUSIONS: Minor allele carriers of the
      skin cancer gene INPP5A modified the odds of arsenic-induced skin lesions in both
      main and replicative populations. Genetic variation in INPP5A appears to have a
      role in susceptibility to arsenic toxicity.

PMID- 25759211
TI  - MUC1-mediated motility in breast cancer: a review highlighting the role of the
      MUC1/ICAM-1/Src signaling triad.
AB  - Breast cancer is the most common cancer in women with the leading cause of death
      being metastasis, the spread of cancer to distant organs. For those patients with
      high-risk estrogen receptor positive (ER+) breast cancer, an increased expression
      of the glycoprotein MUC1 is associated with resistance to anti-hormonal therapy,
      metastasis and death. Tumor cells may use MUC1 to metastasize by exploiting the
      vascular adhesion pathways used by leukocytes during the inflammatory response.
      MUC1 is a type 1 transmembrane protein whose cytoplasmic tail acts as a scaffold
      for several signaling pathways including the non-receptor kinase Src, a signaling
      molecule involved in cell differentiation, proliferation, adhesion and motility.
      This review will highlight our current knowledge of how MUC1/ICAM-1 binding can
      lead to the recruitment and activation of Src and propose a novel role for lipid
      raft microdomains in this promigratory signaling. Improved understanding of the
      mechanism of metastases and the underlying signaling cascade is a prerequisite to
      the discovery of therapeutic targets to prevent metastasis and death in ER+
      breast cancer patients. 

PMID- 25759214
TI  - Boosting antibody developability through rational sequence optimization.
AB  - The application of monoclonal antibodies as commercial therapeutics poses
      substantial demands on stability and properties of an antibody. Therapeutic
      molecules that exhibit favorable properties increase the success rate in
      development. However, it is not yet fully understood how the protein sequences of
      an antibody translates into favorable in vitro molecule properties. In this work,
      computational design strategies based on heuristic sequence analysis were used to
      systematically modify an antibody that exhibited a tendency to precipitation in
      vitro. The resulting series of closely related antibodies showed improved
      stability as assessed by biophysical methods and long-term stability experiments.
      As a notable observation, expression levels also improved in comparison with the
      wild-type candidate. The methods employed to optimize the protein sequences, as
      well as the biophysical data used to determine the effect on stability under
      conditions commonly used in the formulation of therapeutic proteins, are
      described. Together, the experimental and computational data led to consistent
      conclusions regarding the effect of the introduced mutations. Our approach
      exemplifies how computational methods can be used to guide antibody optimization
      for increased stability. 

PMID- 25759217
TI  - Distal myasthenia gravis presenting as isolated distal myopathy.

PMID- 25759215
TI  - Lysyl oxidase-like 2 represses Notch1 expression in the skin to promote squamous
      cell carcinoma progression.
AB  - Lysyl oxidase-like 2 (LOXL2) is involved in a wide range of physiological and
      pathological processes, including fibrosis and tumor progression, implicating
      intracellular and extracellular functions. To explore the specific in vivo role
      of LOXL2 in physiological and tumor contexts, we generated conditional gain- and
      loss-of-function mouse models. Germ-line deletion of Loxl2 promotes lethality in
      half of newborn mice mainly associated to congenital heart defects, while Loxl2
      overexpression triggers male sterility due to epididymal dysfunction caused by
      epithelial disorganization, fibrosis and acute inflammation. Remarkably, when
      challenged to chemical skin carcinogenesis, Loxl2-overexpressing mice increased
      tumor burden and malignant progression, while Loxl2-deficient mice exhibit the
      opposite phenotypes. Loxl2 levels in premalignant tumors negatively correlate
      with expression of epidermal differentiation markers and components of the Notch1
      pathway. We show that LOXL2 is a direct repressor of NOTCH1. Additionally, we
      identify an exclusive expression pattern between LOXL2 and members of the
      canonical NOTCH1 pathway in human HNSCC. Our data identify for the first time
      novel LOXL2 roles in tissue homeostasis and support it as a target for SCC
      therapy.

PMID- 25759218
TI  - [Premalignant lesions of gallbladder].

PMID- 25759216
TI  - Snai1 regulates cell lineage allocation and stem cell maintenance in the mouse
      intestinal epithelium.
AB  - Snail family members regulate epithelial-to-mesenchymal transition (EMT) during
      invasion of intestinal tumours, but their role in normal intestinal homeostasis
      is unknown. Studies in breast and skin epithelia indicate that Snail proteins
      promote an undifferentiated state. Here, we demonstrate that conditional knockout
      of Snai1 in the intestinal epithelium results in apoptotic loss of crypt base
      columnar stem cells and bias towards differentiation of secretory lineages. In
      vitro organoid cultures derived from Snai1 conditional knockout mice also undergo
      apoptosis when Snai1 is deleted. Conversely, ectopic expression of Snai1 in the
      intestinal epithelium in vivo results in the expansion of the crypt base columnar
      cell pool and a decrease in secretory enteroendocrine and Paneth cells. Following
      conditional deletion of Snai1, the intestinal epithelium fails to produce a
      proliferative response following radiation-induced damage indicating a
      fundamental requirement for Snai1 in epithelial regeneration. These results
      demonstrate that Snai1 is required for regulation of lineage choice, maintenance
      of CBC stem cells and regeneration of the intestinal epithelium following damage.

PMID- 25759219
TI  - [Diagnosis and management for gallbladder polyps].

PMID- 25759220
TI  - [Adenomyomatosis of the gallbladder -pathogenesis, diagnosis, and management].

PMID- 25759221
TI  - [Diagnosis and surgical treatment of early gallbladder cancer].

PMID- 25759222
TI  - [Diagnosis and treatment of gallbladder cancer].

PMID- 25759223
TI  - [Clinical characteristics of patients with pneumatosis cystoides intestinalis].
AB  - Pneumatosis cystoides intestinalis (PCI) is a relatively rare disease in which
      multilocular or linear pneumatic cysts develop under the mucosa or serosa of the
      intestinal wall. We conducted a retrospective analysis to investigate the
      clinical characteristics of 68 patients with PCI. Hepatic portal venous gas
      (HPVG) was present in 9 patients, 8 of which had underlying intestinal tract
      necrosis. In most patients, PCI was mild and asymptomatic and resolved
      spontaneously. The main treatment strategy for PCI is conservative therapy.
      However, in cases complicated by HPVG, the presence of underlying intestinal
      tract necrosis must be considered in order to promptly determine whether
      emergency surgery is required. 

PMID- 25759224
TI  - [A case report of food-induced ileus requiring two emergency laparotomies in one
      year].
AB  - A 58-year-old woman completely edentulous man was transported to our hospital by
      ambulance with complaints of abdominal pain and vomiting. Abdominal computed
      tomography revealed multiple objects in the dilated ileum. An emergency
      laparotomy was performed and a diagnosis of ileus caused by ingestion of lotus
      root was established. We advised the patient to obtain and wear dentures.
      However, she did not comply and continued to swallow food without chewing. After
      11 months, she was readmitted with the same symptoms. A second emergency
      laparotomy also revealed food-induced ileus. No recurrence of food-induced ileus
      has occurred after the patient agreed to wearing dentures. When encountering
      patients presenting with ileus, the patient's diet and eating habits should be
      verified, and the condition of the teeth at the time of diagnosis should be
      evaluated. Encouragement of patients to improve eating habits, along with
      adequate dental care, sufficiently prevents food-induced ileus. 

PMID- 25759225
TI  - [Three cases of enteroenteric intussusception examined by three-dimensional
      computed tomography enteroclysis].
AB  - Three-dimensional computed tomography (3D CT) enteroclysis or virtual enteroscopy
      is a novel technique to explore the entire small bowel using a modified protocol
      of virtual colonoscopy by inflating the small bowel with air. In our hospital,
      the procedure is performed routinely for cases with suspected gross lesions. We
      performed 3D CT enteroclysis for three cases with enteroenteric intussusception
      bowel. The lesions associated with intussusception were identified, single
      incision laparoscopic surgery was performed, and diagnoses of lipoma and Peutz
      Jeghers polyp were made in two cases. 3D CT enteroclysis did not reveal any
      associated lesion in the third case. This was followed by an intraoperative
      exploration during gastrectomy for stomach cancer, but no intestinal lesion was
      found. A diagnosis of idiopathic intussusception and its spontaneous release was
      made, and no recurrence was observed during the follow-up period. 3D CT
      enteroclysis seems to be an appropriate modality for the evaluation of
      enteroenteric intussusception. 

PMID- 25759226
TI  - [Successful resection of a gastric aberrant pancreas causing gastrointestinal
      bleeding by laparoscopy and endoscopy cooperative surgery].
AB  - A man in his 50s was admitted to our hospital for treatment of hematemesis.
      Endoscopy revealed arterial bleeding from a gastric submucosal tumor and
      endoscopic hemostasis was successful. However, surgical resection was
      contemplated to prevent recurrent bleeding and for making a definitive diagnosis.
      Surgical resection was eventually performed by laparoscopy and endoscopy
      cooperative surgery (LECS), and the tumor was pathologically diagnosed to be a
      gastric aberrant pancreas. We think that LECS is suitable for a gastric aberrant
      pancreas causing gastrointestinal bleeding, because the procedure is effective
      for tumor resection with minimal removal of the stomach wall. 

PMID- 25759227
TI  - [A case of primary micropapillary carcinoma of the jejunum].
AB  - Micropapillary carcinoma (MPC) has been recently reported as a variant of
      invasive breast carcinoma. MPC is also known to be an aggressive variant of
      adenocarcinoma, and it is associated with poor prognosis and a high propensity
      for lymphovascular invasion and lymph node metastases. MPC of the breast, urinary
      bladder, and lung has been reported relatively frequently; however, there have
      been few reports on gastrointestinal MPC. Furthermore, MPC of the small bowel has
      not been reported yet. Here we report a case of MPC of the jejunum. A female
      septuagenarian was admitted because of anorexia and weight loss. We established a
      diagnosis of primary jejunal cancer and resected the duodenum and a part of the
      jejunum. Histologically, the tumor consisted of adenocarcinoma with moderate to
      poor differentiation. Among the carcinoma cells, approximately 10% formed small
      papillary neoplastic cell clusters surrounded by clear spaces, suggesting a
      diagnosis of MPC. We present the details of the case along with a review of
      relevant literature. 

PMID- 25759228
TI  - [A case of skeletal muscle metastasis on the left thigh after esophagectomy for
      esophageal adenocarcinoma in Barrett' s esophagus].
AB  - We report the case of a 45-year-old man with advanced esophageal adenocarcinoma
      in Barrett's esophagus. After neoadjuvant chemotherapy using S-1, docetaxel, and
      cisplatin, the patient underwent thoracoscopic esophagectomy with a two-field
      lymph node dissection and reconstruction with a gastric tube through the
      posterior mediastinal route. The pathological stage was CT-pT4 (diaphragm), ly2,
      v1, CT-pN1, CT-pStage IVa. Fourteen months after the operation, the patient
      complained of pain in his left thigh with a palpable indurated mass that was
      increasing in size. Needle biopsy specimens revealed skeletal muscle metastasis
      of the adenocarcinoma. The metastastic lesion was resected and local control was
      achieved successfully for 13 months, after which the patient died because of
      intrabronchial bleeding. 

PMID- 25759229
TI  - [Subcutaneous continuous injection of octreotide decreased the tumor marker
      levels and induced cystic necrosis of the tumors in a case of pancreatic
      neuroendocrine tumor with multiple hepatic metastases].
AB  - For symptom alleviation, subcutaneous continuous injection of octreotide was
      administered to a patient with pancreatic neuroendocrine tumor (NET) accompanied
      by multiple hepatic metastases and ascites. The level of the tumor marker neuron
      specific enolase decreased to the normal range and cystic necrosis of the tumors
      was confirmed. There have been some reports on the antineoplastic effects of
      octreotide on pancreatic NET; therefore, octreotide appears to be a valid option
      as a therapeutic agent in patients with highly advanced pancreatic NET, in whom
      administration of molecular targeted or anticancer agents is difficult because of
      a poor general status.

PMID- 25759230
TI  - [Use of dexmedetomidine hydrochloride as a sedative during local therapy for
      hepatocellular carcinoma].
AB  - Sedation using dexmedetomidine hydrochloride (DEX) was administered to patients
      with hepatocellular carcinoma (HCC) prior to local therapy. Case 1 was a 58-year
      old man undergoing radiofrequency ablation in combination with transcatheter
      arterial chemoembolization for HCC in S3. In accordance with the package insert,
      the initial loading dose was set at 6 MUg/kg/hour. Although a favorable sedative
      effect was achieved, his blood pressure and pulse rate decreased. Case 2 was a 79
      year-old woman undergoing percutaneous ethanol injection therapy for HCC in S6.
      Half the initial loading dose indicated in the package insert (3 MUg/kg/hour) was
      administered, but the sedative effect was appreciable. No marked blood pressure
      or pulse rate decreases were observed. We believe that the use of DEX as a
      sedative agent in local therapy for HCC can be expected to increase. However, the
      optimal dose setting for DEX requires further examination. 

PMID- 25759231
TI  - Pituitary stalk thickening on MRI: when is the best time to re-scan and how long
      should we continue re-scanning for?
AB  - Magnetic resonance imaging (MRI) has proved to be an essential tool in the
      assessment of pituitary stalk lesions including lymphocytic infundibulo
      hypophysitis, Langerhans cell histiocytosis (LCH), germ cell tumours,
      nongerminomatous germ cell tumours, pituicytomas and other tumours, metastases
      from lymphoma or breast cancer, Wegener's hypophysitis, neurosarcoidosis and
      inflammatory infiltrations by infectious diseases. The diagnosis of lesions
      determining pituitary stalk thickness is challenging, and the identification of
      the underlying condition may require a long-term follow-up. Thus, clinicians
      should readily recognize that, when the diagnosis of central diabetes insipidus
      has been established, specific MRI sequences should be used in the assessment of
      the hypothalamic-pituitary region, and whole-brain evaluation is recommended. For
      clinical practice, a timely diagnosis is advisable to avoid central nervous
      system damage, pituitary defects and the risk of dissemination of germ cell
      tumours or organ involvement by LCH. Proper aetiological diagnosis can be
      achieved via a series of steps that start with careful observation of several
      neuroimaging predictors and endocrine dysfunction and then progress to more
      sophisticated and advanced imaging techniques. 

PMID- 25759232
TI  - The effect of blue light on periodontal biofilm growth in vitro.
AB  - We have previously shown that blue light eliminates the black-pigmented oral
      bacteria Porphyromonas gingivalis, Prevotella intermedia, Prevotella nigrescens,
      and Prevotella melaninogenica. In the present study, the in vitro
      photosensitivity of the above black-pigmented microorganisms and four
      Fusobacteria species (Fusobacterium nucleatum ss. nucleatum, F. nucleatum ss.
      vincentii, F. nucleatum ss. polymorphum, Fusobacterium periodonticum) was
      investigated in pure cultures and human dental plaque suspensions. We also tested
      the hypothesis that phototargeting the above eight key periodontopathogens in
      plaque-derived biofilms in vitro would control growth within the dental biofilm
      environment. Cultures of the eight bacteria were exposed to blue light at 455 nm
      with power density of 80 mW/cm2 and energy fluence of 4.8 J/cm2. High-performance
      liquid chromatography (HPLC) analysis of bacteria was performed to demonstrate
      the presence and amounts of porphyrin molecules within microorganisms.
      Suspensions of human dental plaque bacteria were also exposed once to blue light
      at 455 nm with power density of 50 mW/cm2 and energy fluence of 12 J/cm2.
      Microbial biofilms developed from the same plaque were exposed to 455 nm blue
      light at 50 mW/cm2 once daily for 4 min (12 J/cm2) over a period of 3 days (4
      exposures) in order to investigate the cumulative action of phototherapy on the
      eight photosensitive pathogens as well as on biofilm growth. Bacterial growth was
      evaluated using the colony-forming unit (CFU) assay. The selective phototargeting
      of pathogens was studied using whole genomic probes in the checkerboard DNA-DNA
      format. In cultures, all eight species showed significant growth reduction (p <
      0.05). HPLC demonstrated various porphyrin patterns and amounts of porphyrins in
      bacteria. Following phototherapy, the mean survival fractions were reduced by
      28.5 and 48.2% in plaque suspensions and biofilms, respectively, (p < 0.05). DNA
      probe analysis showed significant reduction in relative abundances of the eight
      bacteria as a group in plaque suspensions and biofilms. The cumulative blue light
      treatment suppressed biofilm growth in vitro. This may introduce a new avenue of
      prophylactic treatment for periodontal diseases.

PMID- 25759233
TI  - Evaluation of low-level laser therapy, platelet-rich plasma, and their
      combination on the healing of Achilles tendon in rabbits.
AB  - Tendon repair is still one of the challenges for rehabilitation. Various
      treatments for tendon injuries have been used in recent decade. This study was
      established to investigate the effects of low-level laser therapy (LLLT),
      platelet-rich plasma (PRP) treatment alone, and using combined method on the
      healing of Achilles tendon in rabbits. Seventy-two healthy mature male white New
      Zealand rabbits were divided randomly into four groups of 18 animals each:
      control: partial tenotomy with no treatment, only 1 mL normal saline was injected
      on days 1, 8, and 15 at the site of splitting; PRP: partial tenotomy with PRP
      treatment on days 1, 8, and 15 at the site of splitting; LLLT: partial tenotomy
      with LLLT (K30 hand-held probe, AZOR, Technica, Russia, 650 nm, 30 mW, surface
      area = 1 cm(2), 60 S/cm(2), energy density = 1.8 J/cm(2)) for 15 consecutive
      days; LLLT + PRP: partial tenotomy with LLLT + PRP. At the end of trial, the
      rabbits were euthanatized and tendon specimens were harvested and were submitted
      for histopathological evaluation, hydroxyproline levels, and biomechanical
      measurement. The Tukey post hoc test was performed. The results for these
      parameters showed that PRP or LLLT alone has significant advantages over
      untreated animals (P < 0.05). Furthermore, it was found that the combined
      treatment with PRP and LLLT is even more efficient. There was no significant
      difference (P > 0.05) between the two groups of LLLT and PRP. However, the
      treatments combining PRP and LLLT showed significant results in comparison of PRP
      or LLLT alone (P < 0.05). Our results demonstrate that the healing time of
      injured tendon decreases by using the two therapies combined.

PMID- 25759234
TI  - Imaging results of multi-modal ultrasound computerized tomography system designed
      for breast diagnosis.
AB  - Nowadays, in the era of common computerization, transmission and reflection
      methods are intensively developed in addition to improving classical ultrasound
      methods (US) for imaging of tissue structure, in particular ultrasound
      transmission tomography UTT (analogous to computed tomography CT which uses X
      rays) and reflection tomography URT (based on the synthetic aperture method used
      in radar imaging techniques). This paper presents and analyses the results of
      ultrasound transmission tomography imaging of the internal structure of the
      female breast biopsy phantom CIRS Model 052A and the results of the ultrasound
      reflection tomography imaging of a wire sample. Imaging was performed using a
      multi-modal ultrasound computerized tomography system developed with the
      participation of a private investor. The results were compared with the results
      of imaging obtained using dual energy CT, MR mammography and conventional US
      method. The obtained results indicate that the developed UTT and URT methods,
      after the acceleration of the scanning process, thus enabling in vivo
      examination, may be successfully used for detection and detailed characterization
      of breast lesions in women. 

PMID- 25759235
TI  - Cognitive rehabilitation group intervention for breast cancer survivors: results
      of a randomized clinical trial.
AB  - PURPOSE: We conducted a randomized clinical trial evaluating the efficacy of a
      cognitive rehabilitation (CR) intervention compared with a wait list (WL) control
      condition on cognitive complaints, neuropsychological and brain functioning in
      breast cancer survivors (BCS). METHODS: The small group intervention of five
      sessions included psychoeducation and cognitive exercises. ELIGIBILITY: Disease
      free BCS with cognitive complaints, diagnosed with stage I, II or III breast
      cancer, completed primary treatment 18 months to 5 years earlier. Neurocognitive
      test data and cognitive complaints on the Patient's Assessment of Own Functioning
      Inventory (PAOFI) were assessed at baseline (T1), immediately post-intervention
      (T2), and 2 months later (T3). A subgroup of participants underwent resting state
      quantitative electroencephalography (qEEG) at all three assessment time points.
      RESULTS: Forty-eight participants [mean age (SD) 53.8 (8.2)] completed T1
      assessments, and 29 participants had analyzable qEEG data. The CR group improved
      significantly over time compared with the WL group on PAOFI total and memory
      scores (both p = .01) and on Rey Auditory Verbal Learning Test (RAVLT) total
      (trials I-V) (p = .02) and RAVLT delayed recall (p = .007) scores. On qEEG, the
      CR group showed a significant decrease in delta 'slow wave' power (p = .02) and
      an increase in the frontal distribution of alpha power (p = .04) from T1 to T2.
      CONCLUSIONS: BCS in the CR group showed immediate and sustained improvements in
      self-reported cognitive complaints and memory functioning on neurocognitive
      testing. Results of the qEEG substudy provide some support for neurophysiological
      changes underlying the intervention. Copyright (c) 2015 John Wiley & Sons, Ltd.

PMID- 25759237
TI  - Association of Laparoscopic Surgeons of Great Britain and Ireland (ALSGBI),
      Annual Scientific Meeting, Aberdeen, United Kingdom, 27-28 November 2014 :
      Scientific Papers.

PMID- 25759236
TI  - Do height and weight affect the feasibility of single-incision laparoscopic
      cholecystectomy?
AB  - BACKGROUND: Laparoscopic cholecystectomy is the gold standard for gallbladder
      removal and the most common laparoscopic procedure worldwide. Single-incision
      laparoscopic surgery has recently emerged as a less invasive potential
      alternative to conventional three- or four-port laparoscopy. However, the
      feasibility of single-incision laparoscopic cholecystectomy (SILC) remains
      unclear, and there are no rigorous criteria in the literature. Identifying
      patients at risk of failure of this new technique is essential. The aim of our
      study was to determine risk factors that may predict failure of the procedure.
      METHODS: From May 2010 to March 2012, 110 consecutive patients underwent SILC and
      were reviewed retrospectively. The main feasibility criterion was the procedure
      failure rate, defined as addition of supplementary port(s) and prolonged (>60
      min) operative time. The factors evaluated were age, gender, height, weight, body
      mass index, previous abdominal surgery, indication for surgery and gallbladder
      suspension. RESULTS: There was conversion in 16 patients (14.5%), and the
      operative time exceeded 60 min for 20 patients (30.9%). Univariate analysis
      showed a significant independent association between additional port requirement
      and each of weight as a continuous value, weight >=80 kg, BMI >26.5 kg/m(2) and
      height >172 cm. Univariate analysis also showed a significant independent
      association between prolonged operative duration (>60 min) and each of height and
      weight as continuous values, height >172 cm and previous abdominal surgery. In
      the multivariate analysis, only weight remained independently associated with
      additional port requirement, and height remained independently associated with
      prolonged operative duration. CONCLUSION: Preoperative identification of the
      factors increasing the risk of conversion may assist surgeons in making decisions
      concerning the management of patients, including appropriate use of SILC.

PMID- 25759238
TI  - Multifaceted emotion regulation, stress and affect in mothers of young children.
AB  - We tested a novel multi-component emotion self-regulation construct that captured
      physiological (vagal tone), cognitive (reappraisal) and temperament (effortful
      control) aspects of emotion regulation (ER) as a moderator of the link between
      more stressors and greater negative/less positive affectivity (NA and PA). A
      socio-economically diverse sample of 151 women with young children completed
      questionnaires and a laboratory visit (including cognitive and parent-child
      interaction tasks and vagal tone measurement). Women with more stressors had more
      NA and less PA. Furthermore, for NA only, having more stressors was substantially
      associated with NA but only among women with the lowest ER. This pattern was
      evident for the composite as well as individual indicators of ER. Results were
      not attributable to individual differences in executive function. Findings are
      discussed in light of the diathesis-stress model of stress and coping. 

PMID- 25759239
TI  - Genome-wide survey and expression analysis of F-box genes in chickpea.
AB  - BACKGROUND: The F-box genes constitute one of the largest gene families in plants
      involved in degradation of cellular proteins. F-box proteins can recognize a wide
      array of substrates and regulate many important biological processes such as
      embryogenesis, floral development, plant growth and development, biotic and
      abiotic stress, hormonal responses and senescence, among others. However, little
      is known about the F-box genes in the important legume crop, chickpea. The
      available draft genome sequence of chickpea allowed us to conduct a genome-wide
      survey of the F-box gene family in chickpea. RESULTS: A total of 285 F-box genes
      were identified in chickpea which were classified based on their C-terminal
      domain structures into 10 subfamilies. Thirteen putative novel motifs were also
      identified in F-box proteins with no known functional domain at their C-termini.
      The F-box genes were physically mapped on the 8 chickpea chromosomes and
      duplication events were investigated which revealed that the F-box gene family
      expanded largely due to tandem duplications. Phylogenetic analysis classified the
      chickpea F-box genes into 9 clusters. Also, maximum syntenic relationship was
      observed with soybean followed by Medicago truncatula, Lotus japonicus and
      Arabidopsis. Digital expression analysis of F-box genes in various chickpea
      tissues as well as under abiotic stress conditions utilizing the available
      chickpea transcriptome data revealed differential expression patterns with
      several F-box genes specifically expressing in each tissue, few of which were
      validated by using quantitative real-time PCR. CONCLUSIONS: The genome-wide
      analysis of chickpea F-box genes provides new opportunities for characterization
      of candidate F-box genes and elucidation of their function in growth, development
      and stress responses for utilization in chickpea improvement.

PMID- 25759240
TI  - Where You Live Matters: Quality and Racial/Ethnic Disparities in Schizophrenia
      Care in Four State Medicaid Programs.
AB  - OBJECTIVE: To determine whether (a) quality in schizophrenia care varies by
      race/ethnicity and over time and (b) these patterns differ across counties within
      states. DATA SOURCES: Medicaid claims data from California, Florida, New York,
      and North Carolina during 2002-2008. STUDY DESIGN: We studied black, Latino, and
      white Medicaid beneficiaries with schizophrenia. Hierarchical regression models,
      by state, quantified person and county effects of race/ethnicity and year on a
      composite quality measure, adjusting for person-level characteristics. PRINCIPAL
      FINDINGS: Overall, our cohort included 164,014 person-years (41-61 percent non
      whites), corresponding to 98,400 beneficiaries. Relative to whites, quality was
      lower for blacks in every state and also lower for Latinos except in North
      Carolina. Temporal improvements were observed in California and North Carolina
      only. Within each state, counties differed in quality and disparities. Between
      county variation in the black disparity was larger than between-county variation
      in the Latino disparity in California, and smaller in North Carolina; Latino
      disparities did not vary by county in Florida. In every state, counties differed
      in annual changes in quality; by 2008, no county had narrowed the initial
      disparities. CONCLUSIONS: For Medicaid beneficiaries living in the same state,
      quality and disparities in schizophrenia care are influenced by county of
      residence for reasons beyond patients' characteristics.

PMID- 25759241
TI  - Drug-induced EEG pattern predicts effectiveness of ketamine in treating
      refractory status epilepticus.
AB  - Refractory status epilepticus (RSE) can lack overt clinical manifestation and is
      usually treated with continuous infusion of intravenous anesthetic drugs (IVADs),
      where the use of continuous electroencephalography (cEEG) is imperative. Ketamine
      has recently been shown to be effective in the treatment of RSE. We
      retrospectively review a cohort of 11 patients receiving ketamine as part of
      their treatment regimen for RSE. We report on the presence of a characteristic
      EEG rhythm consisting of a generalized archiform theta to beta rhythms (7-20 Hz)
      appearing after ketamine administration. This pattern was seen in five patients,
      four of whom achieved successful resolution of RSE. Ketamine-induced EEG pattern
      may serve as a biomarker predictive of successful treatment outcome in RSE.

PMID- 25759242
TI  - Inhibition of NF-kappaB activity in the hypothalamic paraventricular nucleus
      attenuates hypertension and cardiac hypertrophy by modulating cytokines and
      attenuating oxidative stress.
AB  - We hypothesized that chronic inhibition of NF-kappaB activity in the hypothalamic
      paraventricular nucleus (PVN) delays the progression of hypertension and
      attenuates cardiac hypertrophy by up-regulating anti-inflammatory cytokines,
      reducing pro-inflammatory cytokines (PICs), attenuating nuclear factor-kappaB (NF
      kappaB) p65 and NAD(P)H oxidase in the PVN of young spontaneously hypertensive
      rats (SHR). Young normotensive Wistar-Kyoto (WKY) and SHR rats received bilateral
      PVN infusions with NF-kappaB inhibitor pyrrolidine dithiocarbamate (PDTC) or
      vehicle for 4 weeks. SHR rats had higher mean arterial pressure and cardiac
      hypertrophy as indicated by increased whole heart weight/body weight ratio, whole
      heart weight/tibia length ratio, left ventricular weight/tibia length ratio,
      cardiomyocyte diameters of the left cardiac ventricle, and mRNA expressions of
      cardiac atrial natriuretic peptide (ANP) and beta-myosin heavy chain (beta-MHC).
      These SHR rats had higher PVN levels of proinflammatory cytokines (PICs),
      reactive oxygen species (ROS), the chemokine monocyte chemoattractant protein-1
      (MCP-1), NAD(P)H oxidase activity, mRNA expression of NOX-2 and NOX-4, and lower
      PVN IL-10, and higher plasma levels of PICs and NE, and lower plasma IL-10. PVN
      infusion of NF-kappaB inhibitor PDTC attenuated all these changes. These findings
      suggest that NF-kappaB activation in the PVN increases sympathoexcitation and
      hypertensive response, which are associated with the increases of PICs and
      oxidative stress in the PVN; PVN inhibition of NF-kappaB activity attenuates PICs
      and oxidative stress in the PVN, thereby attenuates hypertension and cardiac
      hypertrophy.

PMID- 25759244
TI  - Allometric scaling for predicting human clearance of bisphenol A.
AB  - The investigation of interspecies differences in bisphenol A (BPA)
      pharmacokinetics (PK) may be useful for translating findings from animal studies
      to humans, identifying major processes involved in BPA clearance mechanisms, and
      predicting BPA PK parameters in man. For the first time, a large range of species
      in terms of body weight, from 0.02 kg (mice) to 495 kg (horses) was used to
      predict BPA clearance in man by an allometric approach. BPA PK was evaluated
      after intravenous administration of BPA in horses, sheep, pigs, dogs, rats and
      mice. A non-compartmental analysis was used to estimate plasma clearance and
      steady state volume of distribution and predict BPA PK parameters in humans from
      allometric scaling. In all the species investigated, BPA plasma clearance was
      high and of the same order of magnitude as their respective hepatic blood flow.
      By an allometric scaling, the human clearance was estimated to be 1.79 L/min
      (equivalent to 25.6 mL/kg.min) with a 95% prediction interval of 0.36 to 8.83
      L/min. Our results support the hypothesis that there are highly efficient and
      hepatic mechanisms of BPA clearance in man.

PMID- 25759243
TI  - Oligofructose protects against arsenic-induced liver injury in a model of
      environment/obesity interaction.
AB  - Arsenic (As) tops the ATSDR list of hazardous environmental chemicals and is
      known to cause liver injury. Although the concentrations of As found in the US
      water supply are generally too low to directly damage the liver, subhepatotoxic
      doses of As sensitize the liver to experimental NAFLD. It is now suspected that
      GI microbiome dysbiosis plays an important role in development of NALFD.
      Importantly, arsenic has also been shown to alter the microbiome. The purpose of
      the current study was to test the hypothesis that the prebiotic oligofructose
      (OFC) protects against enhanced liver injury caused by As in experimental NAFLD.
      Male C57Bl6/J mice were fed low fat diet (LFD), high fat diet (HFD), or HFD
      containing oligofructose (OFC) during concomitant exposure to either tap water or
      As-containing water (4.9ppm as sodium arsenite) for 10weeks. HFD significantly
      increased body mass and caused fatty liver injury, as characterized by an
      increased liver weight-to-body weight ratio, histologic changes and
      transaminases. As observed previously, As enhanced HFD-induced liver damage,
      which was characterized by enhanced inflammation. OFC supplementation protected
      against the enhanced liver damage caused by As in the presence of HFD.
      Interestingly, arsenic, HFD and OFC all caused unique changes to the gut flora.
      These data support previous findings that low concentrations of As enhance liver
      damage caused by high fat diet. Furthermore, these results indicate that these
      effects of arsenic may be mediated, at least in part, by GI tract dysbiosis and
      that prebiotic supplementation may confer significant protective effects.

PMID- 25759246
TI  - Magnetic resonance imaging of rectal cancer: staging and restaging evaluation.
AB  - Magnetic resonance imaging is used to non-invasively stage and restage rectal
      adenocarcinomas. Accurate staging is important as the depth of tumor extension
      and the presence or absence of lymph node metastases determines if an individual
      will undergo preoperative neoadjuvant chemoradiation. Accurate description of
      tumor location is important for presurgical planning. The relationship of the
      tumor to the anal sphincter in addition to the depth of local invasion determines
      the surgical approach used for resection. High-resolution T2-weighted imaging is
      the primary sequence used for initial staging. The addition of diffusion-weighted
      imaging improves accuracy in the assessment of treatment response on restaging
      scans. Approximately 10%-30% of individuals will experience a complete pathologic
      response following chemoradiation with no residual viable tumor found in the
      resected specimen at histopathologic assessment. In some centers, individuals
      with no residual tumor visible on restaging MR who are thought to be at high
      operative risk are monitored with serial imaging and a "watch and wait" approach
      in lieu of resection. Normal rectal anatomy, MR technique utilized for staging
      and restaging scans, and TMN staging are reviewed. An overview of surgical
      techniques used for resection including newer, minimally invasive endoluminal
      techniques is included. 

PMID- 25759245
TI  - Sex-specific patterns and deregulation of endocrine pathways in the gene
      expression profiles of Bangladeshi adults exposed to arsenic contaminated
      drinking water.
AB  - Arsenic contamination of drinking water occurs globally and is associated with
      numerous diseases including skin, lung and bladder cancers, and cardiovascular
      disease. Recent research indicates that arsenic may be an endocrine disruptor.
      This study was conducted to evaluate the nature of gene expression changes among
      males and females exposed to arsenic contaminated water in Bangladesh at high and
      low doses. Twenty-nine (55% male) Bangladeshi adults with water arsenic exposure
      ranging from 50 to 1000 MUg/L were selected from the Folic Acid Creatinine Trial.
      RNA was extracted from peripheral blood mononuclear cells for gene expression
      profiling using Affymetrix 1.0 ST arrays. Differentially expressed genes were
      assessed between high and low exposure groups for males and females separately
      and findings were validated using quantitative real-time PCR. There were 534 and
      645 differentially expressed genes (p<0.05) in the peripheral blood mononuclear
      cells of males and females, respectively, when high and low water arsenic
      exposure groups were compared. Only 43 genes overlapped between the two sexes,
      with 29 changing in opposite directions. Despite the difference in gene sets both
      males and females exhibited common biological changes including deregulation of
      17beta-hydroxysteroid dehydrogenase enzymes, deregulation of genes downstream of
      Sp1 (specificity protein 1) transcription factor, and prediction of estrogen
      receptor alpha as a key hub in cardiovascular networks. Arsenic-exposed adults
      exhibit sex-specific gene expression profiles that implicate involvement of the
      endocrine system. Due to arsenic's possible role as an endocrine disruptor,
      exposure thresholds for arsenic may require different parameters for males and
      females.

PMID- 25759247
TI  - Genome-guided investigation of plant natural product biosynthesis.
AB  - The medicinal plant Madagascar periwinkle, Catharanthus roseus (L.) G. Don,
      produces hundreds of biologically active monoterpene-derived indole alkaloid
      (MIA) metabolites and is the sole source of the potent, expensive anti-cancer
      compounds vinblastine and vincristine. Access to a genome sequence would enable
      insights into the biochemistry, control, and evolution of genes responsible for
      MIA biosynthesis. However, generation of a near-complete, scaffolded genome is
      prohibitive to small research communities due to the expense, time, and expertise
      required. In this study, we generated a genome assembly for C. roseus that
      provides a near-comprehensive representation of the genic space that revealed the
      genomic context of key points within the MIA biosynthetic pathway including
      physically clustered genes, tandem gene duplication, expression sub
      functionalization, and putative neo-functionalization. The genome sequence also
      facilitated high resolution co-expression analyses that revealed three distinct
      clusters of co-expression within the components of the MIA pathway. Coordinated
      biosynthesis of precursors and intermediates throughout the pathway appear to be
      a feature of vinblastine/vincristine biosynthesis. The C. roseus genome also
      revealed localization of enzyme-rich genic regions and transporters near known
      biosynthetic enzymes, highlighting how even a draft genome sequence can empower
      the study of high-value specialized metabolites. 

PMID- 25759249
TI  - Liu et al. suspect that Zhu et al. (2015) may have underestimated dissolved
      organic nitrogen (N) but overestimated total particulate N in wet deposition in
      China.
AB  - In a recent publication in the journal Science of the Total Environment, Zhu et
      al. (2015) reported the composition, spatial patterns, and factors influencing
      atmospheric wet nitrogen (N) deposition based on one year's data from 41
      monitoring sites in China. We suspect their results may largely underestimate
      dissolved organic N (DON) but overestimate total particulate N (TPN) in wet
      deposition due to the uncertainty resulting from the sampling, storage and
      analysis methods in their study. Our suspicions are based mainly on our
      experience from earlier measurements and the literature. We therefore suggest
      that enhanced data quality control on atmospheric N deposition measurements
      should be taken into account in future studies. 

PMID- 25759248
TI  - A Web-based, computer-tailored smoking prevention program to prevent children
      from starting to smoke after transferring to secondary school: randomized
      controlled trial.
AB  - BACKGROUND: Smoking prevalence rates among Dutch children increase rapidly after
      they transit to secondary school, in particular among children with a low
      socioeconomic status (SES). Web-based, computer-tailored programs supplemented
      with prompt messages may be able to empower children to prevent them from
      starting to smoke when they transit to secondary school. OBJECTIVE: The main aim
      of this study is to evaluate whether computer-tailored feedback messages, with
      and without prompt messages, are effective in decreasing children's smoking
      intentions and smoking behavior after 12 and 25 months of follow-up. METHODS:
      Data were gathered at baseline (T0), and after 12 months (T1) and 25 months (T2)
      of follow-up of a smoking prevention intervention program called Fun without
      Smokes. A total of 162 schools were randomly allocated to a no-intervention
      control group, an intervention prompt group, or an intervention no-prompt group.
      A total of 3213 children aged 10 to 12 years old participated in the study and
      completed a Web-based questionnaire assessing their smoking intention, smoking
      behavior, and sociocognitive factors, such as attitude, social influence, and
      self-efficacy, related to smoking. After completion, children in the intervention
      groups received computer-tailored feedback messages in their own email inbox and
      those messages could be accessed on the intervention website. Children in the
      prompt group received prompt messages, via email and short message service (SMS)
      text messaging, to stimulate them to reuse the intervention website with
      nonsmoking content. Multilevel logistic regression analyses were performed using
      multiple imputations to assess the program effects on smoking intention and
      smoking behavior at T1 and T2. RESULTS: A total of 3213 children participated in
      the Fun without Smokes study at T0. Between T0 and T1 a total of 1067 children
      out of the original 3213 (33.21%) dropped out of the study. Between T0 and T2 the
      number of children that did not participate in the final measurement was 1730 out
      of the original 3213 (53.84%). No significant program effects were observed for
      any of the intervention groups compared to the control group at T1 for the
      intention to engage in smoking-prompt, OR 0.67 (95% CI 0.30-1.50), no-prompt, OR
      0.76 (95% CI 0.34-1.67)-or for smoking behavior-prompt, OR 1.13 (95% CI 0.13
      9.98), no-prompt, OR 0.50 (95% CI 0.04-5.59). Similar nonsignificant program
      effects were found at T2 for the intention to start smoking-prompt, OR 0.78 (95%
      CI 0.26-2.32), no-prompt, OR 1.31 (95% CI 0.45-3.82)-and smoking behavior-prompt,
      OR 0.53 (95% CI 0.12-2.47), no-prompt, OR 1.01 (95% CI 0.24-4.21). CONCLUSIONS:
      This study showed that the Web-based, computer-tailored feedback messages with
      and without prompt messages were not effective in modifying children's smoking
      intentions and smoking behavior as compared to no information. Future smoking
      prevention interventions are recommended to start closer to the age of actual
      smoking uptake. Furthermore, future studies on Web-based, computer-tailored
      smoking prevention programs should focus on assessing and controlling exposure to
      the educational content and the response to the prompt messages. TRIAL
      REGISTRATION: Netherlands Trial Register NTR3116;
      http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=3116 (Archived by
      WebCite at http://www.webcitation.org/6O0wQYuPI).

PMID- 25759250
TI  - My road to alternative splicing control: from simple paths to loops and
      interconnections.
AB  - With the functional importance of alternative splicing being validated in nearly
      every mammalian biological system and implicated in many human diseases, it is
      now crucial to identify the molecular programs that control the production of
      splice variants. In this article, I will survey how our knowledge of the basic
      principles of alternative splicing control evolved over the last 25 years. I will
      also describe how investigation of the splicing control of an apoptotic regulator
      led us to identify novel effectors and revealed the existence of converging
      pathways linking splicing decisions to DNA damage. Finally, I will review how our
      efforts at developing tools designed to monitor and redirect splicing helped
      assess the impact of misregulated splicing in cancer. 

PMID- 25759251
TI  - Choice-correlated activity fluctuations underlie learning of neuronal category
      representation.
AB  - The ability to categorize stimuli into discrete behaviourally relevant groups is
      an essential cognitive function. To elucidate the neural mechanisms underlying
      categorization, we constructed a cortical circuit model that is capable of
      learning a motion categorization task through reward-dependent plasticity. Here
      we show that stable category representations develop in neurons intermediate to
      sensory and decision layers if they exhibit choice-correlated activity
      fluctuations (choice probability). In the model, choice probability and task
      specific interneuronal correlations emerge from plasticity of top-down
      projections from decision neurons. Specific model predictions are confirmed by
      analysis of single-neuron activity from the monkey parietal cortex, which reveals
      a mixture of directional and categorical tuning, and a positive correlation
      between category selectivity and choice probability. Beyond demonstrating a
      circuit mechanism for categorization, the present work suggests a key role of
      plastic top-down feedback in simultaneously shaping both neural tuning and
      correlated neural variability. 

PMID- 25759258
TI  - Merkel cell carcinoma of the head and neck: emphasizing the risk of
      undertreatment.
AB  - Merkel cell carcinoma (MCC) is a rare primary cutaneous neuroendocrine carcinoma.
      It occurs predominantly in the head and neck area and often behaves aggressively.
      In this single-institution retrospective observational cohort study, we describe
      the results of a treatment strategy that we developed over the past decades.
      Endpoints of this study were local, regional and distant control, disease
      specific survival and overall survival. In total 47 patients with head and neck
      MCC, diagnosed in the Netherlands Cancer Institute-Antoni van Leeuwenhoek (NKI
      AvL) between 1984 and 2012, were included in this study. Local tumor control was
      82 % (95 % CI 71-95 %) at 5 years. Regional lymph node metastases were found at
      the moment of diagnosis in 13 cases (28 %). In the group of patients who were
      initially cN0, the 5-year regional control was 80 % (68-95 %). The 5-year
      metastasis-free interval probability was 80 % (68-94 %). The disease-specific
      survival (DSS) at 5 years was 70 % (56-86 %). An overall survival of 54 % (40-72
      %) was found at 5-year follow-up and of 37 % (23-59 %) at 10-year follow-up.
      Univariable Cox regression analysis of many clinical and pathological variables
      did not identify any predictors for DSS. The MCC has a high propensity for
      locoregional and distant spread in the head and neck region. Undertreatment,
      especially of the lymph nodes in the neck, is a serious problem as regional
      (micro)metastasis are common even in T1 tumors. Future research will have to
      elucidate the role of the sentinel lymph node procedure versus the elective
      selective node dissection and standardized elective local and regional
      radiotherapy in the head and neck area.

PMID- 25759259
TI  - The use of magnetic resonance imaging for studying female sexual function: A
      review.
AB  - Many would agree that there are two quintessential sexual organs in the female:
      the clitoris and the brain. Using non-invasive techniques of magnetic resonance
      imaging (MRI), investigators have gained insight into the mental and physical
      factors involved in female sexual function. Since only the external clitoral
      glans is easily accessible for direct measurement, the complete anatomy of the
      clitoris (including the internal components-paired corpora, crura, and bulbs) has
      only recently been described, with MRI providing the most sensitive way of
      distinguishing among the various soft tissue planes. Average sizes of clitoral
      structures and average distances between the clitoral complex and other pelvic
      landmarks have been measured. These measurements have been correlated with female
      sexual function: a longer distance between the clitoral complex and the vaginal
      lumen correlates with poorer sexual function, consistent with prior imaging
      studies. However, whether clitoral size influences function is debatable, so
      further studies are needed. Physiological investigations have demonstrated that
      female arousal disorder is unlikely to be due to inadequate genital engorgement.
      Some consider the brain to be the ultimate sexual organ, and several recent
      studies have used functional MRI (fMRI) to reveal sexual excitability in the
      brain. The normal sexual response requires deactivation of the frontal lobe and
      activation of the instinctual limbic system of the midbrain. As MR technology
      continues to improve, the mysteries of female sexuality will be further
      unraveled.

PMID- 25759260
TI  - Causal evidence between monsoon and evolution of rhizomyine rodents.
AB  - The modern Asian monsoonal systems are currently believed to have originated
      around the end of the Oligocene following a crucial step of uplift of the Tibetan
      Himalayan highlands. Although monsoon possibly drove the evolution of many mammal
      lineages during the Neogene, no evidence thereof has been provided so far. We
      examined the evolutionary history of a clade of rodents, the Rhizomyinae, in
      conjunction with our current knowledge of monsoon fluctuations over time. The
      macroevolutionary dynamics of rhizomyines were analyzed within a well-constrained
      phylogenetic framework coupled with biogeographic and evolutionary rate studies.
      The evolutionary novelties developed by these rodents were surveyed in parallel
      with the fluctuations of the Indian monsoon so as to evaluate synchroneity and
      postulate causal relationships. We showed the existence of three drops in
      biodiversity during the evolution of rhizomyines, all of which reflected elevated
      extinction rates. Our results demonstrated linkage of monsoon variations with the
      evolution and biogeography of rhizomyines. Paradoxically, the evolution of
      rhizomyines was accelerated during the phases of weakening of the monsoons, not
      of strengthening, most probably because at those intervals forest habitats
      declined, which triggered extinction and progressive specialization toward a
      burrowing existence. 

PMID- 25759261
TI  - Effects of acute cooling on fish electroretinogram: a comparative study.
AB  - Temperature dependence of electroretinogram (ERG) was investigated in 3 fish
      species occupying different habitats--dogfish shark (Scyliorhinus canicula),
      Prussian carp (Carassius gibelio) and European eel (Anguilla anguilla). Acute
      cooling of the shark isolated eyecup from 23 degrees C down to 6 degrees C
      induced suppression of the electroretinographic b-wave--a complete degradation of
      this component was observed at 6 degrees C. On the other hand, photoreceptor
      component of the ERG, the negative late receptor potential was not affected by
      cooling. The fact that the suppression of the dogfish shark b-wave at low
      temperatures was as a rule irreversible testifies about breakdown of neural
      retinal function at cold temperature extremes. Although in vivo experiments on
      immobilized Prussian carps have never resulted in complete deterioration of the b
      wave at low temperatures, significant suppression of this ERG component by
      cooling was detected. Suppressing the effect of low temperatures on Prussian carp
      ERG might be due to the fact that C. gibelio, as well as other cyprinids, can be
      characterized as a warmwater species preferring temperatures well above cold
      extremes. The ERG of the eel, the third examined species, exhibited the strongest
      resistance to extremely low temperatures. During acute cooling of in situ eyecup
      preparations of migrating silver eels from 30 degrees C down to 2 degrees C the
      form of ERG became wider, but the amplitude of the b-wave only slightly
      decreased. High tolerance of eel b-wave to cold extremes shown in our study
      complies with ecological data confirming eurythermia in migrating silver eels
      remarkably adapted to cold-water environment as well.

PMID- 25759262
TI  - Extension of the established period of diacetyl adaptation by oxygen
      intermediates in the nematode Caenorhabditis elegans.
AB  - After pre-exposure to the odorant diacetyl, the nematode Caenorhabditis elegans
      showed a decline in chemotactic responses to diacetyl, a phenomenon known as
      diacetyl adaptation. In the present study, we found that the established period
      of diacetyl adaptation in nematodes increased with the breeding temperature. When
      wild-type (N2) nematodes were bred at 15 degrees C, adaptation was observed from
      the young adult (YA) to the 3-day-old adult that is reached 3 days after the YA
      stage. On breeding nematodes at 20 degrees C and 25 degrees C, adaptation was
      observed between the YA and 5-day-old adult and between the YA and the 7-day-old
      adult, respectively. Breeding temperature has been shown to correlate with the
      rate of aging in nematodes, which is related to the level of oxygen consumption.
      Accordingly, long-lived isp-1 and clk-1 mutants that demonstrate decreased levels
      of oxygen consumption showed a shorter established period of adaptation than N2
      nematodes, whereas short-lived gas-1 and mev-1 mutants that have a hypersensitive
      response to oxygen showed a longer period of adaptation than the N2. Moreover,
      the established period of diacetyl adaptation in N2 nematodes was shortened by
      the antioxidant alpha-lipoic acid. These results suggest that oxygen
      intermediates, which are produced by oxygen consumption, play a significant role
      in diacetyl adaptation. Although this is only one of many factors that regulate
      diacetyl adaptation, such as the release of neurotransmitters and changes in
      intracellular conditions, the acquisition of this adaptation requires an increase
      in the intensity of moderate oxygen signals.

PMID- 25759263
TI  - Zooming in on the small: the plasticity of striatal dendritic spines in L-DOPA
      induced dyskinesia.
AB  - The spiny dendrites of striatal projection neurons integrate synaptic inputs of
      different origins to regulate movement. It has long been known that these
      dendrites lose spines and display atrophic features in Parkinson's disease (PD),
      but the significance of these morphological changes has remained unknown. Some
      recent studies reveal a remarkable structural plasticity of striatal spines in
      parkinsonian rodents treated with L-3,4-dihydroxyphenylalanine (L-DOPA), and they
      demonstrate an association between this plasticity and the development of
      dyskinesia. These studies used different approaches and animal models, which
      possibly explains why they emphasize different plastic changes as being most
      closely linked to dyskinesia (such as a growth of new spines in neurons of the
      indirect pathway, or a loss of spines in neurons of the direct pathway, or the
      appearance of spines with aberrant synaptic features). Clearly, further
      investigations are required to reconcile these intriguing findings and integrate
      them in a coherent pathophysiological model. Nevertheless, these studies may mark
      the beginning of a new era for dyskinesia research. In addition to addressing
      neurochemical and molecular events that trigger involuntary movements, there is a
      need to better understand the long-lasting structural reorganization of cells and
      circuits that maintain the brain in a "dyskinesia-prone" state. This may lead to
      the identification of new efficacious approaches to prevent the complications of
      dopaminergic therapies in PD.

PMID- 25759264
TI  - Y2O3:Yb3+/Er3+ Hollow Spheres with Controlled Inner Structures and Enhanced
      Upconverted Photoluminescence.
AB  - Multishell Y2 O3 :Yb(3+) /Er(3+) hollow spheres with uniform morphologies and
      controllable inner structures are prepared successfully by using a glucose
      template hydrothermal process followed by temperature-programmed calcination.
      Much enhanced upconverted photoluminescence of these Y2 O3 :Yb(3+) /Er(3+) are
      observed, which are due to the multiple reflections and the enhanced light
      harvesting efficiency of the NIR light resulting from the special features of the
      multishell structures. 

PMID- 25759265
TI  - Management of chronic pain: seek symptoms of post-traumatic stress disorder.

PMID- 25759266
TI  - Kidney injury molecule-1 protects against Galpha12 activation and tissue damage
      in renal ischemia-reperfusion injury.
AB  - Ischemic acute kidney injury is a serious untreatable condition. Activation of
      the G protein alpha12 (Galpha12) subunit by reactive oxygen species is a major
      cause of tissue damage during renal ischemia-reperfusion injury. Kidney injury
      molecule-1 (KIM-1) is a transmembrane glycoprotein that is highly up-regulated
      during acute kidney injury, but the physiologic significance of this up
      regulation is unclear. Here, we report for the first time that Kim-1 inhibits
      Galpha12 activation and protects mice against renal ischemia-reperfusion injury.
      We reveal that Kim-1 physically interacts with and inhibits cellular Galpha12
      activation after inflammatory stimuli, including reactive oxygen species, by
      blocking GTP binding to Galpha12. Compared with Kim-1(+/+) mice, Kim-1(-/-) mice
      exhibited greater Galpha12 and downstream Src activation both in primary tubular
      epithelial cells after in vitro stimulation with H2O2 and in whole kidneys after
      unilateral renal artery clamping. Finally, we show that Kim-1-deficient mice had
      more severe kidney dysfunction and tissue damage after bilateral renal artery
      clamping, compared with wild-type mice. Our results suggest that KIM-1 is an
      endogenous protective mechanism against renal ischemia-reperfusion injury through
      inhibition of Galpha12.

PMID- 25759268
TI  - Peroxidase enzymes regulate collagen extracellular matrix biosynthesis.
AB  - Myeloperoxidase and eosinophil peroxidase are heme-containing enzymes often
      physically associated with fibrotic tissue and cancer in various organs, without
      any direct involvement in promoting fibroblast recruitment and extracellular
      matrix (ECM) biosynthesis at these sites. We report herein novel findings that
      show peroxidase enzymes possess a well-conserved profibrogenic capacity to
      stimulate the migration of fibroblastic cells and promote their ability to
      secrete collagenous proteins to generate a functional ECM both in vitro and in
      vivo. Mechanistic studies conducted using cultured fibroblasts show that these
      cells are capable of rapidly binding and internalizing both myeloperoxidase and
      eosinophil peroxidase. Peroxidase enzymes stimulate collagen biosynthesis at a
      post-translational level in a prolyl 4-hydroxylase-dependent manner that does not
      require ascorbic acid. This response was blocked by the irreversible
      myeloperoxidase inhibitor 4-amino-benzoic acid hydrazide, indicating peroxidase
      catalytic activity is essential for collagen biosynthesis. These results suggest
      that peroxidase enzymes, such as myeloperoxidase and eosinophil peroxidase, may
      play a fundamental role in regulating the recruitment of fibroblast and the
      biosynthesis of collagen ECM at sites of normal tissue repair and fibrosis, with
      enormous implications for many disease states where infiltrating inflammatory
      cells deposit peroxidases.

PMID- 25759267
TI  - S100A8/A9 (calprotectin) is critical for development of glomerulonephritis and
      promotes inflammatory leukocyte-renal cell interactions.
AB  - Glomerulonephritis is a common cause of end-stage renal disease. Infiltrating
      leukocytes interacting with renal cells play a critical role during the
      initiation and progression of glomerulonephritis, but the exact mechanisms are
      not clearly defined. By using the murine model of nephrotoxic nephritis, we
      investigated the role of S100A8/A9 [myeloid-related protein (MRP) 8/14,
      calprotectin] in promoting glomerulonephritis. In nephrotoxic nephritis, wild
      type (WT) mice with glomerulonephritis have elevated serum levels of S100A8/A9,
      whereas mice deficient in MRP14 (S100a9(-/-)), and hence S100A8/A9, are
      significantly protected from disease. By using bone marrow transplants, we showed
      that MRP14 deficiency is required in both the hemopoietic and intrinsic cells for
      the protective effect. In vitro, both the WT bone marrow-derived macrophages and
      renal mesangial cells stimulated with S100A8/A9 secrete IL-6, CXCL1, and tumor
      necrosis factor alpha; however, Mrp14(-/-) cells exhibit significantly blunted
      proinflammatory responses. The interaction of WT bone marrow-derived macrophages
      with renal microvascular endothelial cells results in increased levels of
      monocyte chemotactic protein 1, IL-8, and IL-6 cytokines, which is attenuated in
      Mrp14(-/-) bone marrow-derived macrophages. Data shows that S100A8/A9 plays a
      critical role during glomerulonephritis, exerting and amplifying autocrine and
      paracrine proinflammatory effects on bone marrow-derived macrophages, renal
      endothelial cells, and mesangial cells. Therefore, complete S100A8/A9 blockade
      may be a new therapeutic target in glomerulonephritis.

PMID- 25759269
TI  - 'Nocturnal noises': an isolated stridor in an adolescent.
AB  - An 18-year-old man presented to primary care with a 2-year history of exclusively
      nocturnal 'noisy breathing'. He was otherwise asymptomatic. He had never smoked
      and was previously healthy. Spirometry showed a severely obstructive picture with
      forced expiratory volume in 1 s (FEV1) 1.87 L (44% predicted), forced vital
      capacity (FVC) 4.0 L (80%) and FEV1/FVC ratio of 47%. A diagnosis of asthma was
      suspected and a trial of inhaled bronchodilators and corticosteroids was
      initiated. Failure to improve symptoms led to referral to the Respiratory Clinic,
      where his mother replayed a recording of the 'noisy breathing' on her mobile
      phone. Subsequent examination revealed a stridor on expiration. Flow volume loop
      showed a plateau of the expiratory limb, consistent with intrathoracic upper
      airway obstruction. CT of the thorax revealed a massively dilated oesophagus,
      filled with food residue, reflecting an achalasia, causing lower tracheal
      compression. He is now being considered for a myotomy procedure. 

PMID- 25759270
TI  - Large rhinolith causing nasal obstruction.
AB  - Rhinoliths are calcified masses located in the nasal cavity and may cause
      symptoms such as nasal obstruction, fetid odour and facial pain. They are usually
      diagnosed incidentally on radiographic examinations or depending on the symptoms.
      In this paper we report a 27-year-old Caucasian woman with a calcified mass in
      the right nasal cavity causing nasal obstruction, anosmia and facial pain. The
      calcified mass was removed by endonasal approach. 

PMID- 25759271
TI  - Oral focal mucinosis: a rare case with literature review.
AB  - Oral focal mucinosis (OFM) is an unusual disease that affects diverse localised
      areas of the mouth, where the connective tissue undergoes focal degeneration. It
      was described for the first time by Tomich in 1974. It presents as an
      asymptomatic pedunculated or sessile growth, commonly on the gingiva, with most
      cases being in women. Its pathogenesis is linked to overproduction of hyaluronic
      acid by fibroblasts during collagen production, ensuing in focal myxoid
      degeneration. It has no characteristic features and diagnosis depends on
      histological scrutiny. We report a rare case of oral focal mucinosis affecting a
      54-year-old man who presented with a sessile gingival growth mimicking a common
      tumour-like lesion.

PMID- 25759272
TI  - Acute airway obstruction due to retropharyngeal haematoma caused by a large fish
      bone in a patient with hypertension caused by a pheochromocytoma.
AB  - Retropharyngeal haematoma (RH) is an extremely rare but potentially life
      threatening condition that requires an early diagnosis and immediate management.
      Acute complications arise from compression and obstruction of the upper airway
      and oesophagus with the risk of consecutive aspiration. We present the case of a
      48-year-old man with formation of a RH after accidental ingestion of a large fish
      bone with hypertension as comorbidity caused by a so far undiagnosed
      pheochromocytoma. The patient presented with acute onset of retropharyngeal pain,
      dysphonia and dysphagia secondary to fish bone foreign body ingestion. His
      medical history was significant for uncontrolled hypertension. CT showed a large
      RH extending from the oropharynx to the superior mediastinum. The patient
      underwent emergency tracheostomy, surgical debridement and removal of the fish
      bone. Antihypertensive medication was utilised to control his labile blood
      pressure. The postoperative CT scan revealed an adrenal pheochromocytoma that was
      subsequently resected. 

PMID- 25759273
TI  - Renal denervation for severe hypertension in a small child with Turner syndrome:
      miniaturisation of the procedure and results.
AB  - Sympathetic nervous system hyperactivity plays a role in development and
      progression of hypertension. While renal denervation employing radiofrequency
      devices has been used therapeutically in treating severe hypertension with
      alternate results in adults, few data are available regarding children. We
      treated a 6-year-old girl affected by Turner syndrome presenting severe
      hypertension and an episode of stroke, in spite of treatment with four
      antihypertensive drugs, with sympathetic ablation. The Simplicity device
      (Medtronic, Minneapolis, USA) was adapted to the smaller vessels, allowing a
      tailored approach. After 3 and 6 months of treatment, and beta-blocker
      discontinuation, blood pressure values were set between the 90th and 95th
      centiles for sex and age, and normalised at 12 months. We confirm that renal
      denervation can be used to treat severe hypertension in children; miniaturisation
      of catheter and tailoring the procedure for small vessels allowed a safe
      approach. Progressive improvement of blood pressure had a satisfactory clinical
      impact.

PMID- 25759275
TI  - Speeding up patient flow in rehabilitation.

PMID- 25759274
TI  - Optimal assembly strategies of transcriptome related to ploidies of eukaryotic
      organisms.
AB  - BACKGROUND: Several de novo transcriptome assemblers have been developed recently
      to assemble the short reads generated from the next-generation sequencing
      platforms and different strategies were employed for assembling transcriptomes of
      various eukaryotes without genome sequences. Though there are some comparisons
      among these de novo assembly tools for assembling transcriptomes of different
      eukaryotic organisms, there is no report about the relationship between assembly
      strategies and ploidies of the organisms. RESULTS: When we de novo assembled
      transcriptomes of sweet potato (hexaploid), Trametes gallica (a diploid fungus),
      Oryza meyeriana (a diploid wild rice), five assemblers, including Edena, Oases,
      Soaptrans, IDBA-tran and Trinity, were used in different strategies (Single
      Assembler Single-Parameter, SASP; Single-Assembler Multiple-Parameters, SAMP;
      Combined De novo Transcriptome Assembly, CDTA, that is multiple assembler
      multiple parameter). It was found that CDTA strategy has the best performance
      compared with other two strategies for assembling transcriptome of the hexaploid
      sweet potato, whereas SAMP strategy with assembler Oases is better than other
      strategies for assembling transcriptomes of diploid fungus and the wild rice
      transcriptomes. CONCLUSION: Based on the results from ours and others, it is
      suggested that CDTA strategy is better used for transcriptome assembly of
      polyploidy organisms and SAMP strategy of Oases is outperformed for those diploid
      organisms without genome sequences.

PMID- 25759276
TI  - Functional Outcomes of Tibialis Posterior Tendoscopy With Comparison to Magnetic
      Resonance Imaging.
AB  - BACKGROUND: The purpose of the current study was to report functional outcomes of
      tendoscopy for treatment of tibialis posterior tendon pathology as well as
      compare its diagnostic capability with magnetic resonance imaging (MRI). METHODS:
      Clinical records and MRI of 12 patients who underwent tendoscopy of the tibialis
      posterior tendon (TPT) were retrospectively reviewed. Mean follow-up was 31
      months (range, 26-43 months). Preoperative MRI findings were compared with
      tendoscopic findings to assess the diagnostic agreement between each modality.
      Functional outcomes were assessed using the Foot and Ankle Outcome Score (FAOS)
      and Short Form-12 (SF-12) General Health Questionnaire pre- and postoperatively.
      Mean patient age was 43 years (range, 17-63 years). Mean duration of preoperative
      symptoms was 15.5 months (range, 3-36 months). RESULTS: Pathologies addressed via
      tendoscopy included tenosynovitis, tendinosis, stenosis, tendon subluxation, and
      partial thickness tear (via mini-arthrotomy). Preoperative MRI findings were in
      agreement with tendoscopic findings in 8 of 12 cases (67%). Tendoscopy diagnosed
      and allowed access for treating pathology that was missed on MRI in the remaining
      four cases. The FAOS improved from a mean preoperative score of 58 (range, 36-78)
      to a mean postoperative score of 81 (range, 44-98) (P < .01). The SF-12 score
      improved from a mean preoperative score of 34 (range, 13-51) to a mean
      postoperative score of 51 (range, 21-76) (P = .01). CONCLUSIONS: Although MRI is
      considered an effective imaging technique for tendon pathology, tendoscopy may be
      a more sensitive diagnostic tool. Tendoscopy was an effective minimally invasive
      tool to diagnose and treat tibialis posterior tendon pathology resulting in
      functional improvements in the short-term for early stage TPT dysfunction.
      Further studies comparing tendoscopy with traditional open approaches are
      warranted. LEVEL OF EVIDENCE: Level IV case series.

PMID- 25759277
TI  - Early grade curriculum-based reading measures for students with intellectual
      disability.
AB  - The purpose of this study was to extend previous research on the use of
      curriculum-based measurement (CBM) for students with intellectual disability by
      having 19 special education teachers monitor weekly reading progress of 38
      students with intellectual disability for approximately 15 weeks and examining
      whether students exhibited gains on the progress monitoring measures. In addition
      to the weekly CBM, teachers reported the type and duration of daily reading
      instruction. Data were analyzed to explore relationships between CBM performance
      and reading instruction. Our results indicate that teachers are capable of
      administering and scoring CBM on a weekly basis and that CBM does capture reading
      growth for some students with intellectual disability. Correlations between CBM
      performance and a teacher report of skills taught during reading instruction
      indicate that teachers may be differentiating instruction based on students'
      reading ability. Directions for future research as well as limitations of the
      study are discussed. 

PMID- 25759278
TI  - Ru-Catalyzed asymmetric transfer hydrogenation of alpha-trifluoromethylimines.
AB  - Enantioselective transformation of strong electron-withdrawing acyclic alpha
      trifluoromethylimines to alpha-trifluoromethylamines through a ruthenium
      catalyzed asymmetric transfer hydrogenation has been developed. The method
      described here is a facile catalytic process with sodium formate as a hydrogen
      resource and water-dimethylformamide as a cosolvent. The benefit of this
      enantioselective transformation affords a series of chiral alpha
      trifluoromethylamines with high yields and excellent enantioselectivities (93-99%
      ee) under mild reaction conditions. 

PMID- 25759279
TI  - Prescribing patterns of anti-migraine medicines in South Africa using a claims
      database.
AB  - BACKGROUND: Migraine is an expensive condition impacting on the economically
      active sector of the population. Given the expense of anti-migraine medicine, it
      is important to monitor the impact of generic prescribing and therapeutic
      substitution. OBJECTIVE: The primary aim was to analyse the prescribing patterns
      and cost of anti-migraine medicines to determine the impact of generic
      prescribing and prescribing changes over time. METHOD: A retrospective drug
      utilisation study was conducted on South African private sector medical insurance
      claims data for 2011. Results A total of 797 patients received 1583 anti-migraine
      medicines during 2011. The majority of patients (70.14 %) were females. The
      average age of patients was 41.61 (SD = 14.91) years. Clonidine was the most
      frequently prescribed (49.21 % of prescribing frequency; 25.70 % of cost),
      followed by the triptans [selective serotonin (5-HT1B/1D)-receptor agonists]
      (27.98 % of prescribing frequency; 45.92 % of cost). Five triptans were
      prescribed. The average cost per sumatriptan prescription was the lowest (the
      only triptan with generic equivalents). Rizatriptan was the most frequently
      prescribed triptan (18.51 % of prescribing frequency; 29.15 % of cost).
      CONCLUSION: The results were generally in agreement with previous South African
      studies. The impact of the introduction of newer triptans and of generic
      equivalents on prescribing patterns was clear.

PMID- 25759280
TI  - Bridging the gap between hospital and primary care: the pharmacist home visit.
AB  - Bridging the gap between hospital and primary care is important as transition
      from one healthcare setting to another increases the risk on drug-related
      problems and consequent readmissions. To reduce those risks, pharmacist
      interventions during and after hospitalization have been frequently studied,
      albeit with variable effects. Therefore, in this manuscript we propose a three
      phase approach to structurally address post-discharge drug-related problems.
      First, hospitals need to transfer up-todate medication information to community
      pharmacists. Second, the key phase of this approach consists of adequate follow
      up at the patients' home. Pharmacists need to apply their clinical and
      communication skills to identify and analyze drug-related problems. Finally, to
      prevent and solve identified drug related problems a close collaboration within
      the primary care setting between pharmacists and general practitioners is of
      utmost importance. It is expected that such an approach results in improved
      quality of care and improved patient safety. 

PMID- 25759281
TI  - Rationally designed n-n heterojunction with highly efficient solar hydrogen
      evolution.
AB  - In most of the reported n-n heterojunction photocatalysts, both the conduction
      and valence bands of one semiconductor are more negative than those of the other
      semiconductor. In this work, we designed and synthesized a novel n-n
      heterojunction photocatalyst, namely CdS-ZnWO4 heterojunctions, in which ZnWO4
      has more negative conduction band and more positive valence band than those of
      CdS. The hydrogen evolution rate of CdS-30 mol %-ZnWO4 reaches 31.46 mmol h(-1) 
      g(-1) under visible light, which is approximately 8 and 755 times higher than
      that of pure CdS and ZnWO4 under similar conditions, respectively. The location
      of the surface active sites is researched and a plausible mechanism of
      performance enhancement by the tuning of the structure is proposed based on the
      photoelectrochemical characterization. The results illustrate that this kind of
      nonconventional n-n heterojunctions is also suitable and highly efficient for
      solar hydrogen evolution. 

PMID- 25759282
TI  - The effect of simulated elbow contracture on temporal and distance gait
      parameters.
AB  - BACKGROUND: Elbow contractures can be functionally debilitating. Extensive
      research has been published on treatments to restore elbow motion, but few have
      discussed clinical implications beyond the affected extremity. Reciprocal arm
      swing in normal gait has been shown to increase stability and reduce energy
      expenditure. The importance of arm swing has been clinically demonstrated in
      patients with cerebral palsy, stroke and Parkinson's disease. We hypothesized
      that elbow contractures would result in an abnormal spatio-temporal gait
      parameters. METHODS: Forty volunteer subjects walked on the Gaitmat II which
      provided real-time analysis of temporal and distance gait parameters. Five
      conditions were tested: no brace (control 1), elbow brace unlocked (control 2)
      and brace locked in 30 degrees , 90 degrees  or 120 degrees  flexion (simulating
      fixed elbow contractures). Condition order was randomized for each subject. Each
      condition consisted of five walking trials. RESULTS: All three fixed elbow
      conditions (120 degrees , 90 degrees  and 30 degrees ) demonstrated significantly
      decreased gait velocity (1.37, 1.39 and 1.39m/s) and stride length (1.45, 1.46
      and 1.46m) compared to the control condition (1.42m/s and 1.48m, respectively).
      Single limb stance and double support times were decreased and increased,
      respectively, compared to control. There was no significant difference in cadence
      or limb asymmetry in the three fixed elbow conditions. CONCLUSIONS: Despite well
      established functional limitations in elbow contracture patients and importance
      of arm swing in normal gait, the impact of elbow contractures on gait is unknown.
      This study demonstrates that simulated elbow contracture results in significant
      differences in spatio-temporal gait parameters suggesting that elbow contractures
      have a broader functional impact beyond the affected extremity. LEVEL OF
      EVIDENCE: II.

PMID- 25759283
TI  - Changes of postural control and muscle activation pattern in response to external
      perturbations after neck flexor fatigue in young subjects with and without
      chronic neck pain.
AB  - PURPOSE: Previous studies have identified sensorimotor disturbances and greater
      fatigability of neck muscles in patients with neck pain. The purpose of this
      study was to investigate the effect of neck pain and neck flexor fatigue on
      standing balance following postural perturbations. METHODS: Twenty patients with
      chronic neck pain (CNP) (24.7+/-3.6 year-old) and 20 age-matched asymptomatic
      subjects (22.1+/-2.2 year-old) were recruited. Subjects stood barefoot on a force
      plate and experienced backward perturbations before and after neck flexor
      fatigue. Center of pressure, electromyography of cervical and lumbar muscles, and
      head/trunk accelerations were recorded. Two-way ANOVA (pain*fatigue) was used for
      statistical analysis. RESULTS: CNP group showed larger body sway during quiet
      standing but not during perturbed standing compared with asymptomatic adults. In
      both groups, neck flexor fatigue resulted in greater body sway during the quiet
      standing but smaller body sway during perturbed standing, increased neck muscle
      activations and decreased lumbar muscle activations, as well as increased time to
      maximal head acceleration. CONCLUSIONS: Disturbed balance control was observed in
      CNP patients during the quiet standing. However, a rigid strategy was used to
      minimize the postural sway and to protect the head against backward perturbations
      in both CNP and asymptomatic young adults after neck flexor fatigue. The results
      facilitate the understanding of how the subjects with chronic neck pain and with
      neck muscle fatigue deal with the challenging condition. Further studies are
      needed to verify if such phenomenon could be changed after the intervention of
      specific flexor muscle retraining and balance control exercises.

PMID- 25759284
TI  - Glia-related genes and their contribution to schizophrenia.
AB  - Schizophrenia, a debilitating disease with 1% prevalence in the general
      population, is characterized by major neuropsychiatric symptoms, including
      delusions, hallucinations, and deficits in emotional and social behavior.
      Previous studies have directed their investigations on the mechanism of
      schizophrenia towards neuronal dysfunction and have defined schizophrenia as a
      'neuron-centric' disorder. However, along with the development of genetics and
      systematic biology approaches in recent years, the crucial role of glial cells in
      the brain has also been shown to contribute to the etiopathology of
      schizophrenia. Here, we summarize comprehensive data that support the involvement
      of glial cells (including oligodendrocytes, astrocytes, and microglial cells) in
      schizophrenia and list several acknowledged glia-related genes or molecules
      associated with schizophrenia. Instead of purely an abnormality of neurons in
      schizophrenia, an additional 'glial perspective' provides us a novel and
      promising insight into the causal mechanisms and treatment for this disease. 

PMID- 25759285
TI  - The development of the intrinsic functional connectivity of default network
      subsystems from age 3 to 5.
AB  - In recent years, research on human functional brain imaging using resting-state
      fMRI techniques has been increasingly prevalent. The term "default mode" was
      proposed to describe a baseline or default state of the brain during rest. Recent
      studies suggested that the default mode network (DMN) is comprised of two
      functionally distinct subsystems: a dorsal-medial prefrontal cortex (DMPFC)
      subsystem involved in self-oriented cognition (i.e., theory of mind) and a medial
      temporal lobe (MTL) subsystem engaged in memory and scene construction; both
      subsystems interact with the anterior medial prefrontal cortex (aMPFC) and
      posterior cingulate (PCC) as the core regions of DMN. The present study explored
      the development of DMN core regions and these two subsystems in both hemispheres
      from 3- to 5-year-old children. The analysis of the intrinsic activity showed
      strong developmental changes in both subsystems, and significant changes were
      specifically found in MTL subsystem, but not in DMPFC subsystem, implying
      distinct developmental trajectories for DMN subsystems. We found stronger
      interactions between the DMPFC and MTL subsystems in 5-year-olds, particularly in
      the left subsystems that support the development of environmental adaptation and
      relatively complex mental activities. These results also indicate that there is
      stronger right hemispheric lateralization at age 3, which then changes as
      bilateral development gradually increases through to age 5, suggesting in turn
      the hemispheric dominance in DMN subsystems changing with age. The present
      results provide primary evidence for the development of DMN subsystems in early
      life, which might be closely related to the development of social cognition in
      childhood. 

PMID- 25759286
TI  - Subcortical nuclei volumes in suicidal behavior: nucleus accumbens may modulate
      the lethality of acts.
AB  - Previously, studies have demonstrated cortical impairments in those who complete
      or attempt suicide. Subcortical nuclei have less often been implicated in the
      suicidal vulnerability. In the present study, we investigated, with a specific
      design in a large population, variations in the volume of subcortical structures
      in patients with mood disorders who have attempted suicide. We recruited 253
      participants: 73 suicide attempters with a past history of both mood disorders
      and suicidal act, 89 patient controls with a past history of mood disorders but
      no history of suicidal act, and 91 healthy controls. We collected 1.5 T magnetic
      resonance imaging data from the caudate, pallidum, putamen, nucleus accumbens,
      hippocampus, amygdala, ventral diencephalon, and thalamus. Surface-based
      morphometry (Freesurfer) analysis was used to comprehensively evaluate gray
      matter volumes. In comparison to controls, suicide attempters showed no
      difference in subcortical volumes when controlled for intracranial volume.
      However, within attempters negative correlations between the left (r = -0.35, p =
      0.002), and right (r = -0.41, p < 0.0005) nucleus accumbens volumes and the
      lethality of the last suicidal act were found. Our study found no differences in
      the volume of eight subcortical nuclei between suicide attempters and controls,
      suggesting a lack of association between these regions and suicidal behavior in
      general. However, individual variations in nucleus accumbens structure and
      functioning may modulate the lethality of suicidal acts during a suicidal crisis.
      The known role of nucleus accumbens in action selection toward goals determined
      by the prefrontal cortex, decision-making or mental pain processing are
      hypothesized to be potential explanations.

PMID- 25759287
TI  - Winning is not enough: ventral striatum connectivity during physical aggression.
AB  - Social neuroscience studies have shown that the ventral striatum (VS), a highly
      reward-sensitive brain area, is activated when participants win competitive
      tasks. However, in these settings winning often entails both avoiding punishment
      and punishing the opponent. It is thus unclear whether the rewarding properties
      of winning are mainly associated to punishment avoidance, or if punishing the
      opponent can be additionally gratifying. In the present paper we explored the
      neurophysiological correlates of each outcome, aiming to better understand the
      development of aggression episodes. We previously introduced a competitive
      reaction time task that separates both effects: in half of the won trials,
      participants can physically punish their opponent (active trials), whereas in the
      other half they can only avoid a punishment (passive trials). We performed
      functional connectivity analysis seeded in the VS to test for differential
      network interactions in active compared to passive trials. The VS showed greater
      connectivity with areas involved in reward valuation (orbitofrontal cortex),
      arousal (dorsal thalamus and posterior insula), attention (inferior occipital
      gyrus), and motor control (supplementary motor area) in active compared to
      passive trials, whereas connectivity between the VS and the inferior frontal
      gyrus decreased. Interindividual variability in connectivity strength between VS
      and posterior insula was related to aggressive behavior, whereas connectivity
      between VS and supplementary motor area was related to faster reaction times in
      active trials. Our results suggest that punishing a provoking opponent when
      winning might adaptively favor a "competitive state" in the course of an
      aggressive interaction. 

PMID- 25759288
TI  - Hall and field-effect mobilities in few layered p-WSe2 field-effect transistors.
AB  - Here, we present a temperature (T) dependent comparison between field-effect and
      Hall mobilities in field-effect transistors based on few-layered WSe2 exfoliated
      onto SiO2. Without dielectric engineering and beyond a T-dependent threshold gate
      voltage, we observe maximum hole mobilities approaching 350 cm(2)/Vs at T = 300
      K. The hole Hall mobility reaches a maximum value of 650 cm(2)/Vs as T is lowered
      below ~150 K, indicating that insofar WSe2-based field-effect transistors (FETs)
      display the largest Hall mobilities among the transition metal dichalcogenides.
      The gate capacitance, as extracted from the Hall-effect, reveals the presence of
      spurious charges in the channel, while the two-terminal sheet resistivity
      displays two-dimensional variable-range hopping behavior, indicating carrier
      localization induced by disorder at the interface between WSe2 and SiO2. We argue
      that improvements in the fabrication protocols as, for example, the use of a
      substrate free of dangling bonds are likely to produce WSe2-based FETs displaying
      higher room temperature mobilities, i.e. approaching those of p-doped Si, which
      would make it a suitable candidate for high performance opto-electronics.

PMID- 25759289
TI  - Relaxin: a novel agent for the treatment of acute heart failure.
AB  - Acute heart failure (AHF) is defined by a constellation of signs and symptoms
      that manifest when new or decompensated ventricular dysfunction is triggered by
      an acute precipitant such as excessive preload, afterload, or myocardial
      ischemia. Despite being one of the most frequent causes of hospitalization and
      cardiovascular mortality, little to no progress has been made over the last few
      decades to advance the treatment of AHF. Current mainstays of pharmacotherapy for
      AHF including diuretics, vasodilators, and inotropes can improve symptoms;
      however, no currently approved agent has been shown to provide lasting outcome
      benefit for patients with AHF. First discovered in pregnant women where it is
      known to help with growth of the cervix and assist with the maternal
      cardiovascular and renovascular responses to pregnancy, relaxin is an endogenous
      neurohormone that has novel vasoactive properties. In particular, relaxin is a
      potent vasodilator with a number of pleiotropic effects that may affect cardiac
      remodeling, making relaxin an attractive compound for use in the management of
      AHF. Indeed, in two randomized controlled trials, a single 48-hour infusion of
      relaxin relieved symptoms of AHF with no evidence of major adverse effects. A
      signal of mortality benefit at 180 days was noted in both trials, prompting a
      third trial of relaxin powered for 180-day mortality that is currently under way.
      The pharmacology that underscores the potential benefit of relaxin is discussed
      and insight is provided into future clinical application of this novel drug
      should it prove to be the first therapy capable of reducing mortality in AHF. 

PMID- 25759290
TI  - Aqueous self-assembly of a charged BODIPY amphiphile via nucleation-growth
      mechanism.
AB  - A new amphiphilic boron-dipyrromethene (BODIPY) dye 1 with a hydrophobic wedge at
      the meso-position and two hydrophilic cationic moieties at boron was synthesized.
      Temperature- and concentration-dependent UV/Vis spectroscopic studies in water
      were conducted to explore the self-assembly process of the dye. Detailed analysis
      of the data using two different models (developed by Van der Schoot et al. and
      Goldstein et al. respectively) for cooperative supramolecular polymerization
      indicates distinctly a nucleation-growth mechanism of the aggregation of dye 1
      and the nucleus size (ca. 12-18 molecules) and a cooperativity factor (ca. 0.01)
      could be derived. Further investigation by transmission electron microscopy,
      scanning confocal microscopy, and X-ray diffraction revealed a unique vesicular
      morphology of the aggregates with multilamellar wall structure. Meanwhile, these
      dye vesicles exhibit unique optical characteristics, i.e. red-shifted sharp
      absorption band, narrowed emission linewidth, and increase in fluorescence
      quantum yield, as compared with the monomeric dye. 

PMID- 25759291
TI  - Protective immunity against nervous necrosis virus in convict grouper Epinephelus
      septemfasciatus following vaccination with virus-like particles produced in yeast
      Saccharomyces cerevisiae.
AB  - Infection with nervous necrosis virus (NNV) causes viral nervous necrosis, which
      inflicts serious economic losses in marine fish cultivation. Virus-like particles
      (VLPs) are protein complexes consisting of recombinant virus capsid proteins,
      whose shapes are similar to native virions. VLPs are considered a novel vaccine
      platform because they are not infectious and have the ability to induce
      neutralizing antibodies efficiently. However, there have been few studies of
      protective immune responses employing virus challenge following immunization with
      NNV VLPs, and this is important for evaluating the utility of the vaccine. In the
      present study, we produced red-spotted grouper (Epinephelus akaara) NNV (RGNNV)
      VLPs in Saccharomyces cerevisiae and investigated protective immune responses in
      convict grouper (Epinephelus septemfasciatus) following intraperitoneal injection
      and oral immunization with the RGNNV VLPs. The parenterally administered VLPs
      elicited neutralizing antibody with high efficacy, and provided the fish with
      full protection against RGNNV challenge: 100% of the immunized fish survived
      compared with only 37% of the control fish receiving phosphate-buffered saline.
      RGNNV VLPs administered orally provoked neutralizing antibody systemically and
      conferred protective immunity against virus challenge: however only 57% of the
      fish survived. Our results demonstrate that RGNNV VLP produced in yeast has great
      potential as vaccine in fish. 

PMID- 25759292
TI  - Experimental co-infections of domestic ducks with a virulent Newcastle disease
      virus and low or highly pathogenic avian influenza viruses.
AB  - Infections with avian influenza viruses (AIV) of low and high pathogenicity (LP
      and HP) and Newcastle disease virus (NDV) are commonly reported in domestic ducks
      in many parts of the world. However, it is not clear if co-infections with these
      viruses affect the severity of the diseases they produce, the amount of virus
      shed, and transmission of the viruses. In this study we infected domestic ducks
      with a virulent NDV virus (vNDV) and either a LPAIV or a HPAIV by giving the
      viruses individually, simultaneously, or sequentially two days apart. No clinical
      signs were observed in ducks infected or co-infected with vNDV and LPAIV, but co
      infection decreased the number of ducks shedding vNDV and the amount of virus
      shed (P<0.01) at 4 days post inoculation (dpi). Co-infection did not affect the
      number of birds shedding LPAIV, but more LPAIV was shed at 2 dpi (P<0.0001) from
      ducks inoculated with only LPAIV compared to ducks co-infected with vNDV. Ducks
      that received the HPAIV with the vNDV simultaneously survived fewer days (P<0.05)
      compared to the ducks that received the vNDV two days before the HPAIV. Co
      infection also reduced transmission of vNDV to naive contact ducks housed with
      the inoculated ducks. In conclusion, domestic ducks can become co-infected with
      vNDV and LPAIV with no effect on clinical signs but with reduction of virus
      shedding and transmission. These findings indicate that infection with one virus
      can interfere with replication of another, modifying the pathogenesis and
      transmission of the viruses.

PMID- 25759293
TI  - Presence and new genetic environment of pleuromutilin-lincosamide-streptogramin A
      resistance gene lsa(E) in Erysipelothrix rhusiopathiae of swine origin.
AB  - Erysipelothrix rhusiopathiae is a Gram-positive bacillus that causes erysipelas
      in swine. In recent years, erysipelas infection among swine in China has been
      increasing. A combined resistance phenotype to pleuromutilins, lincosamides, and
      streptogramin A (PLSA phenotype) was found in some E. rhusiopathiae isolates. The
      aim of this study was to identify the resistance genes responsible for the PLSA
      phenotype in E. rhusiopathiae strains and to map the genetic environment of the
      identified resistance gene. A total of 46 E. rhusiopathiae isolates from 31 pig
      farms in China were studied. Minimum inhibitory concentrations (MICs) of 11
      antimicrobial agents were determined by broth microdilution method. Seven were
      highly resistant to tiamulin (MICs 32 MUg/ml) and clindamycin (MICs 64 MUg/ml).
      Resistance genes responsible for the PLSA phenotype were screened by PCR. The
      lsa(E), spw, lnu(B), aadE and aphA3 genes were detected in strains had the PLSA
      phenotype, whereas none was detected in susceptible strains. The genetic
      environment of lsa(E) gene was determined by whole-genome sequencing and
      overlapping PCR assays. A novel multiresistance gene cluster, orf1-aadE-apt-spw
      lsa(E)-lnu(B)-rec-orf2-orf1-aadE-sat4-aphA3, was found. Horizontal gene transfer
      experiments and whole-genome sequencing suggested that the lsa(E)-carrying
      multiresistance gene cluster was located in the chromosome. This is the first
      molecular characterization of PLSA resistance in E. rhusiopathiae. The lsa(E),
      spw and lnu(B) genes were found in E. rhusiopathiae for the first time. A novel
      lsa(E)-carrying multiresistance gene cluster was found. The location of lsa(E) in
      different gene cluster facilitates its persistence and dissemination.

PMID- 25759294
TI  - Characterization of thymus atrophy in calves with subclinical BVD challenged with
      BHV-1.
AB  - Since the thymus is a target organ for the bovine viral diarrhea virus (BVDV),
      our experiment aimed to understand its relationship with the immunosuppressive
      effect by studying the consequences of a previous infection with BVDV on the
      thymus of calves challenged with bovine herpesvirus 1.1 (BHV-1). For this
      purpose, 12 animals were inoculated intranasally with non-cytopathic BVDV-1; 12
      days later, 10 of them were coinfected intranasally with BHV-1. These animals
      were euthanized in batches of two at 0, 1, 2, 4, 7 or 14 dpi with BHV-1. Another
      10 calves were inoculated solely with BHV-1 and euthanized in batches of two at
      1, 2, 4, 7 or 14 dpi with BHV-1; two uninoculated calves were used as negative
      controls. Thymus samples from these animals were processed for viral detection
      and histopathological, immunohistochemical, and ultrastructural studies focused
      on BVDV/BHV-1 antigens, cortex:medulla ratio, apoptosis (TUNEL and caspase-3),
      collagen deposition, and factor VIII endothelial detection. Our study revealed
      the immunohistochemical presence of BVDV antigen in all animals in the BVDV
      infected group, unlike BHV-1 detection, which was observed in animals in both
      infection groups only by molecular techniques. BVDV-preinfected animals showed
      severe atrophic changes associated with reduced cortex:medulla ratio, higher
      presence of cortical apoptosis, and increased collagen deposition and
      vascularization. However, calves solely infected with BHV-1 did not show atrophic
      changes. These findings could affect not only the numbers of circulating and
      local mature T cells but also the T cell-mediated immunity, which seems to be
      impaired during infections with this virus, thus favoring pathogenic effects
      during secondary infections.

PMID- 25759296
TI  - The point of view of medical oncologists.

PMID- 25759297
TI  - Psychosocial needs and well-being issues of long-term survivors and cured cancer
      patients.

PMID- 25759298
TI  - The point of view of patients' organisations.

PMID- 25759299
TI  - Dopamine D2 Modulation of Sign and Goal Tracking in Rats.
AB  - In Pavlovian conditioning, sign- and goal-tracking behaviors represent different
      approaches towards the conditioned stimulus. These behavioral patterns have been
      associated with predictive or incentive properties of the conditioned stimulus,
      with a crucial involvement of the mesolimbic dopamine system. As it is possible
      that sign tracking behavior is more sensitive to dopamine modulation, we
      evaluated the dopamine-dependence of sign- and goal-tracking behavior. We
      assessed responses to both a D2 agonist and an antagonist, and tested performance
      in a behavioral paradigm known to activate dopamine projections and in an animal
      model that affects mesolimbic and mesocortical function. Sign trackers displayed
      a greater sensitivity to a D2 agonist and smaller prepulse inhibition of the
      acoustic startle response than goal trackers, suggesting a reduced inhibitory
      ability. In addition, a neonatal ventral hippocampal lesion resulted in the loss
      of incentive salience of cues in sign trackers. Overall, these data indicate that
      sign-tracking behavior is more heavily controlled by dopamine than goal tracking.

PMID- 25759300
TI  - Ketamine Strengthens CRF-Activated Amygdala Inputs to Basal Dendrites in mPFC
      Layer V Pyramidal Cells in the Prelimbic but not Infralimbic Subregion, A Key
      Suppressor of Stress Responses.
AB  - A single sub-anesthetic dose of ketamine, a short-acting NMDA receptor blocker,
      induces a rapid and prolonged antidepressant effect in treatment-resistant major
      depression. In animal models, ketamine (24 h) reverses depression-like behaviors
      and associated deficits in excitatory postsynaptic currents (EPSCs) generated in
      apical dendritic spines of layer V pyramidal cells of medial prefrontal cortex
      (mPFC). However, little is known about the effects of ketamine on basal
      dendrites. The basal dendrites of layer V cells receive an excitatory input from
      pyramidal cells of the basolateral amygdala (BLA), neurons that are activated by
      the stress hormone CRF. Here we found that CRF induces EPSCs in PFC layer V cells
      and that ketamine enhanced this effect through the mammalian target of rapamycin
      complex 1 synaptogenic pathway; the CRF-induced EPSCs required an intact BLA
      input and were generated primarily in basal dendrites. In contrast to its
      detrimental effects on apical dendritic structure and function, chronic stress
      did not induce a loss of CRF-induced EPSCs in basal dendrites, thereby creating a
      relative imbalance in favor of amygdala inputs. The effects of ketamine were
      complex: ketamine enhanced apical EPSC responses in all mPFC subregions, anterior
      cingulate (AC), prelimbic (PL), and infralimbic (IL) but enhanced CRF-induced
      EPSCs only in AC and PL-responses were unchanged in IL, a critical area for
      suppression of stress responses. We propose that by restoring the strength of
      apical inputs relative to basal amygdala inputs, especially in IL, ketamine would
      ameliorate the hypothesized disproportional negative influence of the amygdala in
      chronic stress and major depression.

PMID- 25759301
TI  - Fluoxetine Administration Exacerbates Oral Tremor and Striatal Dopamine Depletion
      in a Rodent Pharmacological Model of Parkinsonism.
AB  - The cardinal motor symptoms of Parkinson's disease (PD) include resting tremor,
      akinesia, bradykinesia, and rigidity, and these motor abnormalities can be
      modeled in rodents by administration of the VMAT-2 (type-2 vesicular monoamine
      transporter) inhibitor tetrabenazine (9,10-dimethoxy-3-(2-methylpropyl)
      1,3,4,6,7, 11b hexahydrobenzo[a]quinolizin-2-one; TBZ). Depression is also
      commonly associated with PD, and clinical data indicate that selective serotonin
      reuptake inhibitors (SSRIs) such as fluoxetine ((+/-)-N-methyl-gamma-[4
      (trifluoromethyl)phenoxy]benzenepropanamine hydrochloride; FLX) are frequently
      used to treat depression in PD patients. The aim of the present study was to
      characterize the effect of FLX on the motor dysfunctions induced by a low dose of
      TBZ (0.75 mg/kg), and investigate the neural mechanisms involved. This low dose
      of TBZ was selected based on studies with rat models of depressive symptoms. In
      rats, coadministration of FLX (2.5, 5.0, and 10.0 mg/kg) increased TBZ-induced
      oral tremor (tremulous jaw movements), and decreased locomotor activity compared
      with administration of TBZ alone. Coadministration of the serotonin 5-HT2A/2C
      antagonist mianserin (2.5 and 5.0 mg/kg) attenuated the increase in oral tremor
      induced by coadministration of TBZ (0.75 mg/kg) with FLX (5.0 mg/kg). Consistent
      with these behavioral data, coadministration of TBZ and FLX decreased DA tissue
      levels in the rat ventrolateral neostriatum compared with TBZ alone, and
      coadministration of mianserin with TBZ and FLX attenuated this effect, increasing
      DA tissue levels compared with the TBZ/FLX condition. These data suggest that
      SSRI administration in PD patients may result in worsening of motor symptoms, at
      least in part, by exacerbating existing DA depletions through 5-HT2A/2C-mediated
      modulation of DA neurotransmission.

PMID- 25759302
TI  - Input and state estimation for linear systems with a rank-deficient direct
      feedthrough matrix.
AB  - The problem of joint input and state estimation for linear stochastic systems
      with a rank-deficient direct feedthrough matrix is discussed in this paper.
      Results from previous studies only solve the state estimation problem; globally
      optimal estimation of the unknown input is not provided. Based on linear minimum
      variance unbiased estimation, a five-step recursive filter with global optimality
      is proposed to estimate both the unknown input and the state. The relationship
      between the proposed filter and the existing results is addressed. We show that
      the unbiased input estimation does not require any new information or additional
      constraints. Both the state and the unknown input can be estimated under the same
      unbiasedness condition. Global optimalities of both the state estimator and the
      unknown input estimator are proven in the minimum-variance unbiased sense. 

PMID- 25759295
TI  - Italian cancer figures, report 2014: Prevalence and cure of cancer in Italy.
AB  - OBJECTIVES: This Report intends to estimate the total number of people still
      alive in 2010 after cancer diagnosis in Italy, regardless of the time since
      diagnosis, and to project these estimates to 2015. This study is also aimed to
      estimate the number of already cured cancer patients, whose mortality rates have
      become undistinguishable from that of the general population of the same age and
      sex. MATERIALS AND METHODS: The study took advantage of the information from the
      AIRTUM database, which included 29 Cancer Registries (covering 21 million people,
      35% of the Italian population). A total of 1,624,533 cancer cases diagnosed
      between 1976 and 2009 contributed to the study. For each registry, the observed
      prevalence was calculated. Prevalence for lengths of time exceeding the maximum
      duration of the registration and of the complete prevalence were derived by
      applying an estimated correction factor, the completeness index. This index was
      estimated by means of statistical regression models using cancer incidence and
      survival data available in registries with 18 years of observation or more. For
      50 types or combinations of neoplasms, complete prevalence was estimated at
      1.1.2010 as an absolute number and as a proportion per 100,000 inhabitants by
      sex, age group, area of residence, and years since diagnosis. Projections of
      complete prevalence for 1.1.2015 were computed under the assumption of a linear
      trend of the complete prevalence observed until 2010. Validated mixture cure
      models were used to estimate: the cure fraction, that is the proportion of
      patients who, starting from the time of diagnosis, are expected to reach the same
      mortality rate of the general population; the conditional relative survival
      (CRS), that is the cumulative probability of surviving some additional years,
      given that patients already survived a certain number of years; the time to cure,
      that is the number of years necessary so that conditional survival in the
      following five years (5-year CRS) exceeds the conventional threshold of 95%
      (i.e., mortality rates in cancer patients become undistinguishable compared to
      those of the general population); the proportion of patients already cured, i.e.,
      people alive since a number of years exceeding time to cure. RESULTS: As of
      1.1.2010, it was estimated that 2,587,347 people were alive after a cancer
      diagnosis, corresponding to 4.4% of the Italian population. A relevant
      geographical heterogeneity emerged, with a prevalence above 5% in northern
      registries and below 4% in southern areas. Men were 45% of the total (1,154,289)
      and women 55% (1,433,058). In the population aged 75 years or more, the
      proportions of prevalent cases were 20% in males and 13% in females, 11% between
      60 and 74 years of age in both sexes. Nearly 600,000 Italian women were alive
      after a breast cancer diagnosis (41% of all women with this neoplasm), followed
      by women with cancers of the colon rectum (12%), corpus uteri (7%), and thyroid
      (6%). In men, 26% of prevalent cases (295,624) were patients with prostate
      cancer, 16% with either bladder or colon rectum cancer. The projections for
      1.1.2015 are of three million (3,036,741) people alive after a cancer diagnosis,
      4.9% of the Italian population; with a 20% increase for males and 15% for
      females, compared to 2010. The cure fractions were heterogeneous according to
      cancer type and age. Estimates obtained as the sum of cure fractions for all
      cancer types showed that more than 60% of patients diagnosed below the age of 45
      years will reach the same mortality rate of the general population. This
      proportion decreased with increasing age and it was <30% for cancer diagnosed
      after the age of 74 years. It was observed that 60% of all prevalent cases
      (1,543,531 people or 2.6% of overall Italian population) had been diagnosed >5
      years earlier (long-term survivors). Time to cure (5-year CRS>95%) was reached in
      <10 years by patients with cancers of the stomach, colon rectum, pancreas, corpus
      and cervix uteri, brain, and Hodgkin lymphoma. Mortality rates similar to the
      ones reported by the general population were reached after approximately 20 years
      for breast and prostate cancer patients. Five-year CRS remained <95% for >25
      years after cancer diagnosis in patients with liver and larynx cancers, non
      Hodgkin lymphoma, myeloma, and leukaemia. Time to cure was reached by 27% (20% in
      men and 33% in women) of all people living after a cancer diagnosis, defined as
      already cured. CONCLUSIONS: The study showed a steady increase over time (nearly
      +3% per year) of prevalent cases in Italy. A quarter of Italian cancer patients
      alive in 2010 can be considered as already cured. The AIRTUM Report 2014
      describes characteristics of cancer patients and former-patients for 50 cancer
      types or combinations by sex and age. This detailed information promotes the
      conduction of studies aimed at expanding the current knowledge on the quality of
      life of these patients during and after the active phase of treatments
      (prevalence according to health status), on the long-term effects of treatments
      (in particular for paediatric patients), on the cost profile of cancer patients,
      and on rare tumours. All these observations have a high potential impact on
      health planning, clinical practice, and, most of all, patients' perspective.

PMID- 25759304
TI  - Biological characteristics of adipose tissue-derived stem cells labeled with
      amine-surface-modified superparamagnetic iron oxide nanoparticles.
AB  - Cell labeling and tracking are becoming increasingly important areas within the
      field of stem cell transplantation. The ability to track the migration and
      distribution of implanted cells is critical to understanding the beneficial
      effects and mechanisms of stem cell therapy. The present study investigated the
      effects of amine-surface-modified superparamagnetic iron oxide (SPIO)
      nanoparticles on the biological properties of human adipose tissue-derived stem
      cells (hADSCs). Monodisperse hydrophobic magnetite (Fe3 O4 ) nanoparticles were
      prepared using silicon and surface-modified with amine coating. Cell viability,
      proliferation, differentiation potential, and surface marker expression were
      evaluated. The magnetic particles (10-18 nm) displayed high labeling efficiency
      and stability in hADSCs. SPIO-labeled cells produced a hypointense signal and
      were effectively visualized by MRI for up to 21 days. The results of MTT
      proliferation assays and flow cytometry analysis demonstrated that SPIOs were
      biocompatible, viz. the labeling process did not cause cell death or apoptosis
      and had no side effects on cell proliferation. In vivo experiments showed that
      the magnetic particles did not affect liver and kidney function. The successful
      and stable labeling of hADSCs combined with efficient magnetic tropism
      demonstrates that SPIOs are promising candidates for hADSC tracking in hADSC
      based cell therapy applications. 

PMID- 25759303
TI  - Plant nuclear shape is independently determined by the SUN-WIP-WIT2-myosin XI-i
      complex and CRWN1.
AB  - Nuclei undergo dynamic shape changes during plant development, but the mechanism
      is unclear. In Arabidopsis, Sad1/UNC-84 (SUN) proteins, WPP domain-interacting
      proteins (WIPs), WPP domain-interacting tail-anchored proteins (WITs), myosin XI
      i, and CROWDED NUCLEI 1 (CRWN1) have been shown to be essential for nuclear
      elongation in various epidermal cell types. It has been proposed that WITs serve
      as adaptors linking myosin XI-i to the SUN-WIP complex at the nuclear envelope
      (NE). Recently, an interaction between Arabidopsis SUN1 and SUN2 proteins and
      CRWN1, a plant analog of lamins, has been reported. Therefore, the CRWN1-SUN-WIP
      WIT-myosin XI-i interaction may form a linker of the nucleoskeleton to the
      cytoskeleton complex. In this study, we investigate this proposed mechanism in
      detail for nuclei of Arabidopsis root hairs and trichomes. We show that WIT2, but
      not WIT1, plays an essential role in nuclear shape determination by recruiting
      myosin XI-i to the SUN-WIP NE bridges. Compared with SUN2, SUN1 plays a
      predominant role in nuclear shape. The NE localization of SUN1, SUN2, WIP1, and a
      truncated WIT2 does not depend on CRWN1. While crwn1 mutant nuclei are smooth,
      the nuclei of sun or wit mutants are invaginated, similar to the reported myosin
      XI-i mutant phenotype. Together, this indicates that the roles of the respective
      WIT and SUN paralogs have diverged in trichomes and root hairs, and that the SUN
      WIP-WIT2-myosin XI-i complex and CRWN1 independently determine elongated nuclear
      shape. This supports a model of nuclei being shaped both by cytoplasmic forces
      transferred to the NE and by nucleoplasmic filaments formed under the NE. 

PMID- 25759307
TI  - Lifestyle and its influences.

PMID- 25759305
TI  - Validation of the new FIGO staging system (2009) for vulvar cancer in the Chinese
      population.
AB  - OBJECTIVE: A new FIGO staging system for vulvar cancer was issued in 2009. The
      aim of this study was to identify its value in estimating the outcome of patients
      with vulvar squamous cell carcinoma (VSCC) in the Chinese population. METHODS: A
      total of 184 patients who underwent radical surgery for VSCC were recruited.
      Their medical records and pathology slides were reviewed. Disease
      reclassification was conducted according to the FIGO staging system (2009). The
      primary outcomes were cause-specific survival (CSS), relapse-free survival (RFS)
      and overall survival (OS). RESULTS: A total of 76 patients (41.3%) were
      downstaged and no patients were upstaged in the new FIGO staging system (2009).
      The stage distribution was as follows: stage I (99), stage II (13), stage III
      (65) and stage IV (7). According to CSS, the patients were classified into 4
      groups: stage IA (group 1), stage IB/II/IIIA (group 2), stage IIIB (group 3), and
      stage IIIC/IV (group 4) (5-year CSS: 100%, 85%, 34.6% and 0%, respectively). The
      5-year CSS was similar among the patients with stage IB, II and IIIA carcinomas
      (84.4%, 84.6% and 84.8%, respectively, p=0.986), whereas, significant decline of
      the CSS was found with increased substages of stages IIIA, IIIB and IIIC (84.8%,
      34.6%, and 0 respectively, p<0.001). CONCLUSIONS: The 2009 FIGO staging system
      for VSCC displayed good performance for the subdivisions of stage III VSCC, but
      it failed to stratify survival well between stages IB, II and IIIA.

PMID- 25759308
TI  - Music could aid brain development.

PMID- 25759306
TI  - Family physician ethnicity influences quality of diabetes care for Chinese but
      not South Asian patients.
AB  - AIMS: To determine whether sharing the same ethnicity as their family physician
      influenced the quality of diabetes care for Chinese and South Asian patients in
      Ontario, Canada. METHODS: We conducted two related studies: a population-based
      cohort study of Chinese and South Asian patients with incident diabetes using
      health care administrative data (n=49,484), and a cross-sectional study of
      Chinese and South Asian patients with established diabetes using data collected
      directly from their family physicians' clinical records (n=416). In both studies,
      quality of care measures were compared between patients whose family physicians
      were or were not from the same ethnic group. RESULTS: In the cohort study,
      Chinese patients whose family physicians were also Chinese were more likely to
      have a diabetes-related family physician visit and appropriate HbA1c and
      cholesterol testing. In the cross-sectional study, they were more likely to have
      foot examinations, to have microalbuminuria testing, and to achieve recommended
      treatment targets for HbA1c and for LDL-cholesterol. In contrast, for South Asian
      patients, most quality measures in either study did not differ by physician
      ethnicity. CONCLUSIONS: Having a family physician from the same ethnic group was
      associated with better quality of diabetes care for Chinese but not for South
      Asian patients.

PMID- 25759309
TI  - Public less trusting of diet advice from overweight doctors.

PMID- 25759310
TI  - The global crisis of depression: the low of the 21st century?

PMID- 25759311
TI  - The voice of the Royal society for public health.

PMID- 25759312
TI  - Health trainers: a service in transition.

PMID- 25759313
TI  - Diet and Alzheimer's disease.

PMID- 25759314
TI  - Perspectives on Ebola screening at ports of entry in the UK.

PMID- 25759315
TI  - The indigenous health gap: raising awareness and changing attitudes.

PMID- 25759316
TI  - War on sodium: the case of Korean public health campaigns.

PMID- 25759317
TI  - No incentive for postnatal care in IGMSY.

PMID- 25759318
TI  - New Ebola vaccine trial is underway.

PMID- 25759319
TI  - Physical inactivity may kill more than obesity.

PMID- 25759320
TI  - Modelling the metastatic cascade by in vitro microfluidic platforms.
AB  - The metastatic cascade comprises the following steps in sequential manner: the
      future metastatic cell has to leave the primary tumor mass, degrade the
      surrounding extracellular matrix, extravasate and circulate within in the
      bloodstream. Thereafter it has to attach to the endothelium of a target organ,
      intravasate into the connective tissue and has to proliferate to form a
      clinically detectable metastasis. We overview the in vitro microfluidic platforms
      modelling the metastatic cascade and the evolution towards systems capable of
      recapitulating all the steps by a single comprehensive model. 

PMID- 25759321
TI  - The impact of driving force on electron transfer rates in photovoltaic donor
      acceptor blends.
AB  - The effect of acceptor energy level on electron transfer rate in blends of the
      polymer solar-cell material poly[[4,8-bis[(2-ethylhexyl)oxy]benzo[1,2-b:4,5
      b']dithiophene-2,6-diyl][3-fluoro-2-[(2-ethylhexyl)carbonyl]thieno[3,4
      b]thiophenediyl]] (PTB7) is studied using time-resolved fluorescence. Fast
      electron transfer in less than 2 ps is observed for a driving force between 0.2
      and 0.6 eV and the electron transfer is slower outside this range. This
      dependence is described by Marcus theory with a reorganization energy of ~0.4 eV.

PMID- 25759322
TI  - Nonlinear resonance-assisted tunneling induced by microcavity deformation.
AB  - Noncircular two-dimensional microcavities support directional output and strong
      confinement of light, making them suitable for various photonics applications. It
      is now of primary interest to control the interactions among the cavity modes
      since novel functionality and enhanced light-matter coupling can be realized
      through intermode interactions. However, the interaction Hamiltonian induced by
      cavity deformation is basically unknown, limiting practical utilization of
      intermode interactions. Here we present the first experimental observation of
      resonance-assisted tunneling in a deformed two-dimensional microcavity. It is
      this tunneling mechanism that induces strong inter-mode interactions in mixed
      phase space as their strength can be directly obtained from a separatrix area in
      the phase space of intracavity ray dynamics. A selection rule for strong
      interactions is also found in terms of angular quantum numbers. Our findings,
      applicable to other physical systems in mixed phase space, make the interaction
      control more accessible. 

PMID- 25759323
TI  - The usefulness of serum troponin levels to predict 1-year survival rates in
      infective endocarditis.
AB  - BACKGROUND AND AIM: Infective endocarditis (IE) is associated with increased
      mortality and morbidity. In this study, we aimed to evaluate the role of troponin
      levels in predicting long-term survival in patients with IE. METHODS: A
      retrospective analysis of the medical database of Yuksek Ihtisas Education and
      Research Hospital was performed to reach the patients that received the diagnosis
      of definite IE according to Duke criteria. Out of 84 definite IE cases, 48
      patients (mean age 45.6 +/- 17.3, 39.6% female) that had troponin T levels
      measured upon hospital admission were included. The survival status of the study
      subjects was assessed during a follow-up period of 1 year. RESULTS: A total of 20
      (41.7%) patients died during the follow-up. Baseline median troponin T levels
      were significantly higher in fatal cases (0.08 [0.02-0.24] ng/ml vs. 0.02 [0.01
      0.04] ng/ml p = 0.003). The optimal troponin T level to detect mortality was 0.05
      ng/ml according to receiver operating characteristic curve (area under the curve
      0.75, 95% Confidence Interval (CI) [0.61-0.9], p = 0.003) with 70% sensitivity
      and 79% specificity. Patient with elevated troponin levels were older, were more
      likely to be male and tended to have enterococcal infection. These patients had
      also higher creatinine levels and increased systolic pulmonary pressures. In the
      multivariate Cox regression analysis, renal failure (hazards ratio (HR) 8.23, CI
      95% 2.53-26.9, p < 0.0001), heart failure (HR 4.48, CI 95% 1.73-11.61, p = 0.002)
      and troponin T >= 0.05 ng/ml (HR 3.11, CI 95% 1.13-8.56, p = 0.03) were
      associated with increased mortality rates. CONCLUSIONS: IE has poor outcome and
      baseline troponin T levels may predict long-term survival rates in these
      patients.

PMID- 25759324
TI  - High prevalence of anti-toxoplasma antibodies and absence of Toxoplasma gondii
      infection risk factors among pregnant women attending routine antenatal care in
      two Hospitals of Addis Ababa, Ethiopia.
AB  - OBJECTIVE: Toxoplasmosis is an infection caused by the protozoan parasite
      Toxoplasma gondii. It is acquired mainly by eating raw or undercooked meat
      containing Toxoplasma gondii tissue cyst, eating food or water contaminated with
      oocyst, and acquiring congenital infection through the placenta. This study was
      conducted to determine the prevalence of toxoplasmosis and assess possible risk
      factors associated with the infection among pregnant women in Addis Ababa,
      Ethiopia. METHOD: Cross sectional study was designed, and 288 serum samples were
      collected from November 1(st) 2010 to January 2011. The serum samples were tested
      for anti- Toxoplasma gondii antibodies using latex agglutination test. The risk
      factors were tested for significance using Bivariate and multivariate analysis. P
      value <0.05 was considered statistically significant. RESULT: 85.4% were positive
      for anti Toxoplasma gondii antibody. No significant association was observed
      between seroprevalence and age, gestational age, socio demographic characters,
      history of abortion, consumption of raw or undercooked meat, consumption of raw
      vegetable, owning of cat, and blood transfusion. CONCLUSION: Prevalence of
      toxoplasmosis among pregnant women in Addis Ababa, Ethiopia is higher than that
      reported from other countries. Efforts to describe risk factors for toxoplasma
      infection among Ethiopians should focus in children.

PMID- 25759325
TI  - Capillary Force-Driven, Hierarchical Co-Assembly of Dandelion-Like Peptide
      Microstructures.
AB  - The wetting and drying of drops on flexible fibers occurs ubiquitously in nature,
      and the capillary force underlying this phenomenon has motivated our great
      interest in learning how to direct supramolecular self-assembly. Here, the
      hierarchical co-assembly of two aromatic peptides, diphenylalanine (FF) and
      ferrocene-diphenylalanine (Fc-FF), is reported via sequential, combinatorial
      assembly. The resulting dandelion-like microstructures have highly complex
      architectures, where FF microtube arrays serve as the scapes and the Fc-FF
      nanofibers serve as the flower heads. Homogeneous FF microtubes with diameters
      tailored between 1 and 9 MUm and wall thickness ranging from 70 to 950 nm are
      initially formed by controlling the degree of supersaturation of the FF and the
      water content. Once the FF microtubes are formed, the growth of the dandelion
      like microstructures is then driven by the capillary force, derived from the
      wetting and drying of the Fc-FF solution on the FF microtubes. This simple and
      ingenious strategy offers many opportunities to develop new and creative methods
      for controlling the hierarchical self-assembly of peptides and thus building
      highly complex nano and microstructures. 

PMID- 25759326
TI  - Functional Characterization of Cucurbitadienol Synthase and Triterpene
      Glycosyltransferase Involved in Biosynthesis of Mogrosides from Siraitia
      grosvenorii.
AB  - Mogrosides, the major bioactive components isolated from the fruits of Siraitia
      grosvenorii, are a family of cucurbitane-type tetracyclic triterpenoid saponins
      that are used worldwide as high-potency sweeteners and possess a variety of
      notable pharmacological activities. Mogrosides are synthesized from 2,3
      oxidosqualene via a series of reactions catalyzed by cucurbitadienol synthase
      (CbQ), Cyt P450s (P450s) and UDP glycosyltransferases (UGTs) in vivo. However,
      the relevant genes have not been characterized to date. In this study, we report
      successful identification of SgCbQ and UGT74AC1, which were previously predicted
      via RNA-sequencing (RNA-seq) and digital gene expression (DGE) profile analysis
      of the fruits of S. grosvenorii. SgCbQ was functionally characterized by
      expression in the lanosterol synthase-deficient yeast strain GIL77 and was found
      to accumulate cucurbitadienol as the sole product. UGT74AC1 was heterologously
      expressed in Escherichia coli as a His-tag protein and it showed specificity for
      mogrol by transfer of a glucose moiety to the C-3 hydroxyl to form mogroside IE
      by in vitro enzymatic activity assays. This study reports the identification of
      CbQ and glycosyltransferase from S. grosvenorii for the first time. The results
      also suggest that RNA-seq, combined with DGE profile analysis, is a promising
      approach for discovery of candidate genes involved in biosynthesis of triterpene
      saponins. 

PMID- 25759327
TI  - Novel Characteristics of Photodamage to PSII in a High-Light-Sensitive
      Symbiodinium Phylotype.
AB  - Dinoflagellates from the genus Symbiodinium form symbiotic relationships with
      many marine invertebrates, including reef-building corals. Symbiodinium is
      genetically diverse, and acquiring suitable Symbiodinium phylotypes is crucial
      for the host to survive in habitat environments, such as high-light conditions.
      The sensitivity of Symbiodinium to high light differs among Symbiodinium
      phylotypes, but the mechanism that controls light sensitivity has not yet been
      fully resolved. In the present study using high-light-tolerant and -sensitive
      Symbiodinium phylotypes, we examined what determines sensitivity to high light.
      In growth experiments under different light intensities, Symbiodinium CS-164
      (clade B1) and CCMP2459 (clade B2) were identified as high-light-tolerant and 
      sensitive phylotypes, respectively. Measurements of the maximum quantum yield of
      photosystem II (PSII) and the maximum photosynthetic oxygen production rate after
      high-light exposure demonstrated that CCMP2459 is more sensitive to
      photoinhibition of PSII than CS-164, and tends to lose maximum photosynthetic
      activity faster. Measurement of photodamage to PSII under light of different
      wavelength ranges demonstrated that PSII in both Symbiodinium phylotypes was
      significantly more sensitive to photodamage under shorter wavelength regions of
      light spectra (<470 nm). Importantly, PSII in CCMP2459, but not CS-164, was also
      sensitive to photodamage under the regions of light spectra around 470-550 and
      630-710 nm, where photosynthetic antenna proteins of Symbiodinium have light
      absorption peaks. This finding indicates that the high-light-sensitive CCMP2459
      has an extra component of photodamage to PSII, resulting in higher sensitivity to
      high light. Our results demonstrate that sensitivity of PSII to photodamage
      differs among Symbiodinium phylotypes and this determines their sensitivity to
      high light. 

PMID- 25759328
TI  - Live Single-Cell Plant Hormone Analysis by Video-Mass Spectrometry.
AB  - Studies have indicated that endogenous concentrations of plant hormones are
      regulated very locally within plants. To understand the mechanisms underlying
      hormone-mediated physiological processes, it is indispensable to know the exact
      hormone concentrations at cellular levels. In the present study, we established a
      system to determine levels of ABA and jasmonoyl-isoleucine (JA-Ile) from single
      cells. Samples taken from a cell of Vicia faba leaves using nano-electrospray
      ionization (ESI) tips under a microscope were directly introduced into mass
      spectrometers by infusion and subjected to tandem mass spectrometry (MS/MS)
      analysis. Stable isotope-labeled [D(6)]ABA or [(13)C(6)]JA-Ile was used as an
      internal standard to compensate ionization efficiencies, which determine the
      amount of ions introduced into mass spectrometers. We detected ABA and JA-Ile
      from single cells of water- and wound-stressed leaves, whereas they were almost
      undetectable in non-stressed single cells. The levels of ABA and JA-Ile found in
      the single-cell analysis were compared with levels found by analysis of purified
      extracts with liquid chromatography-tandem mass spectrometry (LC-MS/MS). These
      results demonstrated that stress-induced accumulation of ABA and JA-Ile could be
      monitored from living single cells.

PMID- 25759329
TI  - Iron Availability Affects Phosphate Deficiency-Mediated Responses, and Evidence
      of Cross-Talk with Auxin and Zinc in Arabidopsis.
AB  - Phosphate (Pi) is pivotal for plant growth and development. Pi deficiency
      triggers local and systemically regulated adaptive responses in Arabidopsis
      thaliana. Inhibition of primary root growth (PRG) and retarded development of
      lateral roots (LRs) are typical local Pi deficiency-mediated responses of the
      root system. Expression of Pi starvation-responsive (PSR) genes is regulated
      systemically. Here, we report the differential influence of iron (Fe)
      availability on local and systemic sensing of Pi by Arabidopsis. P-Fe- condition
      disrupted local Pi sensing, resulting in an elongated primary root (PR). Altered
      Fe homeostasis in the lpsi mutant with aberration in local Pi sensing provided
      circumstantial evidence towards the role of Fe in the maintenance of Pi
      homeostasis. Reporter gene assays, expression analysis of auxin-responsive genes
      (ARGs) and root phenotyping of the arf7arf19 mutant demonstrated the role of Fe
      availability on local Pi deficiency-mediated LR development. In addition, Fe
      availability also exerted a significant influence on PSR genes belonging to
      different functional categories. Together, these results demonstrated a
      substantial influence of Fe availability on Pi deficiency-mediated responses of
      ontogenetically distinct traits of the root system and PSR genes. The study also
      provided evidence of cross-talk between Pi, Fe and Zn, highlighting a complex
      tripartite interaction amongst them for maintaining Pi homeostasis. 

PMID- 25759331
TI  - Cushing disease: where do we stand, where are we heading?

PMID- 25759330
TI  - Paraphilias and paraphilic disorders in Parkinson's disease: A systematic review
      of the literature.
AB  - Paraphilias are intense urges or behaviors involving non-normative sexual
      interests. The newly approved diagnostic criteria in the Diagnostic and
      Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) have established
      that, although paraphilias should not be regarded as inherently pathological,
      they ought to be qualified as paraphilic disorders if resulting in distress,
      impairment, or harm to the affected individual or others. Recent evidence
      documents that both phenomena can emerge as relatively uncommon iatrogenic
      consequences in Parkinson's disease (PD) patients. To outline the clinical
      characteristics of paraphilias and paraphilic disorders in PD patients, we
      summarized the available evidence on these phenomena. The review encompasses all
      studies on paraphilias in PD patients identified by a search on the Pubmed and
      Scopus online databases through May 2014. Twenty-two case reports on a total of
      31 PD patients with paraphilias or paraphilic disorders were identified. These
      phenomena were typically associated with dopaminomimetic treatment (with a mean
      levodopa-equivalent daily dose of 1,303 +/- 823 mg/d) in male patients with motor
      complications, young age at PD onset, and long disease duration. Paraphilias were
      highly concomitant with impulse-control disorders or dopamine dysregulation
      syndrome. Although evidence on paraphilias and paraphilic disorders in PD
      patients remains anecdotal, available data point to these phenomena as likely
      sequelae of high-dose dopaminomimetic treatment. Accordingly, the intensity of
      paraphilic urges is typically attenuated by the reduction of dopaminomimetic
      doses, sometimes in association with atypical antipsychotics. Failure to
      recognize paraphilic disorders may significantly impair the relational
      functioning of the affected PD patients. Practitioners should routinely inquire
      about paraphilias during their clinical assessment of PD patients.

PMID- 25759332
TI  - Multipurpose prevention technologies: the future of HIV and STI protection.
AB  - Every day, more than 1 million people are newly infected with sexually
      transmitted infections (STIs) that can lead to morbidity, mortality, and an
      increased risk of human immunodeficiency virus (HIV) acquisition. Existing
      prevention and management strategies, including behavior change, condom
      promotion, and therapy have not reduced the global incidence and prevalence,
      pointing to the need for novel innovative strategies. This review summarizes
      important issues raised during a satellite session at the first HIV Research for
      Prevention (R4P) conference, held in Cape Town, on October 31, 2014. We explore
      key STIs that are challenging public health today, new biomedical prevention
      approaches including multipurpose prevention technologies (MPTs), and the
      scientific and regulatory hurdles that must be overcome to make combination
      prevention tools a reality. 

PMID- 25759334
TI  - Author's reply to letter by Trewartha and Stokes on available evidence on risk of
      injury in youth rugby.

PMID- 25759335
TI  - "Hell no, they'll think you're mad as a hatter": Illness discourses and their
      implications for patients in mental health practice.
AB  - This article examines how discourses on mental illness are negotiated in mental
      health practice and their implications for the subjective experiences of
      psychiatric patients. Based on a Foucauldian analysis of ethnographic data from
      two mental health institutions in Denmark--an outpatient clinic and an inpatient
      ward--this article identifies three discourses in the institutions: the
      instability discourse, the discourse of "really ill," and the lack of insight
      discourse. This article indicates that patients were required to develop a finely
      tuned and precise sense of the discourses and ways to appear in front of
      professionals if they wished to have a say in their treatment. We suggest that
      the extent to which an individual patient was positioned as ill seemed to rely
      more on his or her ability to navigate the discourses and the psychiatric setting
      than on any objective diagnostic criteria. Thus, we argue that illness discourses
      in mental health practice are not just materialized as static biomedical
      understandings, but are complex and diverse--and have implications for patients'
      possibilities to understand themselves and become understandable to
      professionals.

PMID- 25759333
TI  - Developmental Trajectories of Auditory Cortex Synaptic Structures and Gap
      Prepulse Inhibition of Acoustic Startle Between Early Adolescence and Young
      Adulthood in Mice.
AB  - Cortical excitatory and inhibitory synapses are disrupted in schizophrenia, the
      symptoms of which often emerge during adolescence, when cortical excitatory
      synapses undergo pruning. In auditory cortex, a brain region implicated in
      schizophrenia, little is known about the development of excitatory and inhibitory
      synapses between early adolescence and young adulthood, and how these changes
      impact auditory cortex function. We used immunohistochemistry and quantitative
      fluorescence microscopy to quantify dendritic spines and GAD65-expressing
      inhibitory boutons in auditory cortex of early adolescent, late adolescent, and
      young adult mice. Numbers of spines decreased between early adolescence and young
      adulthood, during which time responses increased in an auditory cortex-dependent
      sensory task, silent gap-prepulse inhibition of the acoustic startle reflex (gap
      PPI). Within-bouton GAD65 protein and GAD65-expressing bouton numbers decreased
      between late adolescence and young adulthood, a delay in onset relative to spine
      and gap-PPI changes. In mice lacking the spine protein kalirin, there were no
      significant changes in spine number, within-bouton GAD65 protein, or gap-PPI
      between adolescence and young adulthood. These results illustrate developmental
      changes in auditory cortex spines, inhibitory boutons, and auditory cortex
      function between adolescence and young adulthood, and provide insights into how
      disrupted adolescent neurodevelopment could contribute to auditory cortex synapse
      pathology and auditory impairments. 

PMID- 25759336
TI  - [The state of the art on nutrition, food safety and food security].
AB  - In Italy, public health is experiencing a phase of crisis. A contraction of
      services and a staff reallocation have affected in particular Food Hygiene
      services. We explored Pubmed and Google Ngram Viewer(c) to define the state of
      the art of research in food and nutritional field from a quantitative point of
      view and we focused on some areas of interest in terms of improvement of
      professional practice. The Italian contribution to food and nutritional research
      is still limited. Our findings seem to demonstrate the need of an alliance
      between the world of research and Public Health services, so as to develop a
      sustainable and effective health system. 

PMID- 25759337
TI  - [The role of ecological studies to evaluate the impact of an enviromental factor
      on health: a case study on the results of the SENTIERI project].
AB  - A case-study regarding the results of the SENTIERI project on the Brescia-Caffaro
      NPCS (National Priority Contaminated Site) is reported. This area has been
      polluted mainly by polychlorinated biphenyls (PCBs), which have been classified
      recently by the International Agency for Research on Cancer as human carcinogens
      (group 1), with sufficient evidence for melanoma and limited for non-Hodgkin
      lymphoma (NHL) and breast cancer. The 3rd report of the SENTIERI project (2014)
      has shown an excess of cancer incidence with respect to the expected, on the
      basis of the incidence rates from the pool of Centre-North Italy cancer
      registries, but a mortality similar to that expected according to the regional
      rates, for melanoma, NHL and breast cancer. Furthermore, a higher than expected
      incidence has been found for various cancers which are not associated a priori
      with PCB exposure. The Brescia Local Health Authority has also carried out an
      analysis of cancer incidence, which has shown an incidence in the area similar to
      other ones in North Italy and a cluster of cases centered on Brescia town for
      melanoma only. A possible explanation of these discrepancies is the use of
      different reference populations for the comparisons (Region and pool of Centre
      North Italy cancer registries), besides possible confounding bias. We discuss
      here the most critical aspects of modern ecological studies, their potential
      information content and interpretation limits. 

PMID- 25759338
TI  - [Primary prevention of cancer and cardiovascular diseases: an overview of
      scientific literature].
AB  - OBJECTIVE: To compare the proportions of effective primary prevention
      interventions for non-communicable diseases with the proportions of effective
      prevention interventions delivered in practice. METHODS: An overview of
      systematic reviews on prevention interventions tackling tobacco smoking, obesity,
      and cardiovascular disease, was carried out. Individual trials were extracted,
      and their results were organised by intervention effectiveness. Medline was
      searched to describe the effectiveness of the interventions implemented in
      practice. RESULTS: We found 11 systematic reviews, 4 focusing on prevention of
      cardiovascular diseases (including 150 trials), 1 on obesity (55), and 6 on
      tobacco smoking (219). Out of all interventions, 34.9% revealed some evidence of
      effectiveness, whereas 3.6% provided evidence of adverse effects. We identified 4
      studies reporting proportions of effective prevention interventions ranging from
      20%to 35%in the United States. A 2008 survey reported 1,501 behavioural
      prevention interventions implemented in Italy, 1% of which was evidence-based.
      DISCUSSION: Only 35% of prevention interventions provided some evidence of
      effectiveness. Some interventions had harmful effects. Most of implemented
      interventions have never been evaluated. Actions are urgently needed to ensure
      that delivered interventions are effective and safe, for example by developing an
      approval system of prevention interventions.

PMID- 25759339
TI  - [Visiting friends and relatives (VFRs) role on imported malaria: a literature
      review].
AB  - OBJECTIVE: In the last decades, increased numbers of travel to tropical
      destinations in combination with the enormous influx of immigrants have led to an
      increased number of imported malaria cases in developed countries. There is a
      group of immigrants regularly resident in malaria free areas, which travel to
      malaria endemic countries to visit their friends and relatives (VFRs). VFRs
      represent a high-risk group of contracting malaria. Publications presenting
      original data on malaria in VFRs were selected for a literature review. METHODS:
      We considered all data regarding prevalence of malaria in VFRs compared to the
      other groups of travelers, length of trip, group characteristics such as age,
      sex, country visited, and adherence to pre-travel recommendations, in particular,
      the compliance on the use of chemoprophylaxis, where such information was
      available. Studies related to malaria importation in VFRs in children and
      pregnant women were also included. RESULTS: Review of the literature revealed
      significant variations in the proportion of VFRs among imported malaria cases
      which may be due to differences in immigrant populations across the reporting
      countries. However, in studies focused on those at higher risk such as children
      and pregnant women, the prevalence of imported malaria was significantly higher
      compared to other types of travelers. DISCUSSION: Adherence to adequate
      preventive measures was low in VFRs. Significant reasons for not seeking pre
      travel advice were economic and cultural issues, fear of the side effects due to
      chemoprophylaxis, and misconception about life-long immunity against malaria, and
      consequently, a low awareness about malaria risk. In order to implement
      preventive strategies focused on this high-risk group, prospective studies, which
      better define determinants of the risk of malaria in VFRs, are needed.

PMID- 25759340
TI  - [Implementation of Italian guidelines on public health genomics in Italy: a
      challenging policy of the NHS].
AB  - BACKGROUND: Genomics and related fields are becoming increasingly relevant in
      health care practice. Italy is the first European country that has a structured
      policy of Public Health Genomics. Nevertheless, what should be the role of
      genomics in a public health perspective and how public health professionals
      should engage with advances in genomics' knowledge and technology, is still not
      entirely clear. METHODS: A description of the regulatory framework made-up by the
      Italian government in the last years is provided. In order to implement the
      national guidelines on Public Health Genomics published in 2013, key issues
      including the ethical, legal and social aspects within an evidence-based
      framework should be warranted and are herewith discussed. CONCLUSIONS: Genomics
      and predictive medicine are considered one of the main intervention areas by the
      National Prevention Plan 2010-2012, and dedicated guidelines were published in
      2013. In order to implement such guidelines, we envisage a coordinated effort
      between stakeholders to guide development in genomic medicine, towards an impact
      on population health. There is also room to implement knowledge on how genomics
      can be integrated into health systems in an appropriate and sustainable way.
      Learning programs are needed to spread knowledge and awareness of genomics
      technology, in particular on genomic testing for complex diseases.

PMID- 25759341
TI  - [European community guidelines and standards in indoor air quality: what
      proposals for Italy].
AB  - Indoor air quality is an issue on which to focus because of the increasing number
      of exposed population and in view of the strong public feeling on this issue.
      This paper reports the rules of EU and several European countries about indoor
      air quality, focusing on the initiatives performed in Italy to respond to WHO
      recommendations. Several EU countries have introduced in their legislation rules
      relating to indoor air quality. At the moment, in Italy, a reference rule has not
      been issued. For this reason, up to date main informations concerning some
      guidelines or reference values in indoor air, to be used for a first comparison,
      are those obtained by the scientific literature, or by the guidelines issued by
      other European countries or, for analogy, by other standard values such as limit
      or reference values regarding outdoor air. Even the EU, while reaffirming the
      priority of energy efficiency measures, recommends healthier indoor environments
      and the development of a specific European strategy on the issue of indoor air
      quality. The National Study Group on indoor pollution of the Italian National
      Health Institute (ISS), is working for the development of shared technical and
      scientific documents, in order to provide greater uniformity of actions at
      national level, waiting for a legal framework for indoor air quality, in the
      light of the indication already produced by the WHO. 

PMID- 25759342
TI  - [New frontiers of education in healthcare].
AB  - Competency is the ability to use a structured set of knowledge, skills, and
      attitudes in a specific professional context, or in professional training. Over
      the past 10 years there has been an acceleration of the trend towards a
      competency-based design of the education of healthcare professionals, rather than
      just defining learning objectives or relying on the content of disciplinary
      programs. The choice for a competency-based curriculum is not only the result of
      a changed pedagogical vision, but also an answer to the request of accountability
      toward society about how are the professionals trained and also to allow
      comparability between universities and nations. In recent years, many
      international initiatives have defined competency models for medicine and more
      specifically for public health. This article summarizes these initiatives,
      putting them in the context of the evolving Italian legislation. 

PMID- 25759343
TI  - [Sustainability and hygiene of building: future perspectives].
AB  - OBJECTIVES: Multiple factors influence individuals' health status. Their impact
      is difficult to quantify as it is their interaction. Aim of the current work is
      to develop guidelines to support designers to promote health in the residential
      environment and to apply them through an evaluation system to certify the level
      of health performance. DESIGN: Politecnico di Milano, in collaboration with the
      Local Health Authorities of Milan and Empoli through analysis of needs
      performance and numerous multidisciplinary meetings, has produced a design guide
      (Healthy Design Guide - HeDe) and an evaluation system to certify the level of
      health performance. This system was tested on the Milan metropolitan area.
      SETTING: The experiment was carried out on a sample of 30 private residences,
      with an overall floor area ranging between 90 and 150 square meters, new or
      recently renovated. RESULTS: The tool works but at the same time it also shows
      that too often design choices are made for aesthetic or economic reasons rather
      than a real need for health and wellness. CONCLUSIONS: It is becoming
      increasingly important to strengthen synergies and multidisciplinary
      collaborations to achieve shared performance indications and to make a systematic
      review of the regulatory tools to protect public health.

PMID- 25759344
TI  - [Control of intubator associated pneumonia in intensive care unit: results of the
      GISIO-SItI SPIN-UTI Project].
AB  - OBJECTIVE: To document reported Intubator Associated Pneumonia (IAP) prevention
      practices in Intensive Care Units (ICUs) and attitudes towards the implementation
      of a measurement system. DESIGN: In the framework of the SPIN-UTI project the
      "Italian Nosocomial Infections Surveillance in ICUs network", two questionnaires
      were made available online. The first was filled out by physicians working in
      ICUs in order to collect data on characteristics of physicians and ICUs, on
      clinical and measurement practices for IAP prevention, and attitudes towards the
      implementation of a measurement system. The second questionnaire was filled out
      for each intubated patient in order to collect data on prevention practices
      during ICU stay. SETTING AND PARTICIPANTS: ICUs participating to the fourth
      edition (2012-2013) of the SPIN-UTI project. MAIN OUTCOME MEASURES: Compliance to
      the component of the European bundle. RESULTS: The components of the bundle for
      the prevention of IAP are implemented, although to a different level, in the 26
      participating ICUs. Overall compliance to all five practices of the European
      bundle has been reported in 21.1% of the 768 included patients. CONCLUSIONS: The
      present survey has documented a large potential for improvement in clinical and
      non-clinical practices aimed at preventing IAP in ICUs.

PMID- 25759345
TI  - [Sero-epidemiology of VZV infection in Italy: impact evaluation of extensive
      vaccination].
AB  - OBJECTIVE: Eight Italian Regions have begun offering vaccination against
      varicella to children aged 13-15 months, with a second dose at 5-6 years of age.
      A serosurvey was conducted to evaluate the impact of extensive vaccination in
      these "pilot" Regions. DESIGN: Samples were collected in compliance with current
      legislation and after the approval of the Ethics Committee. The qualitative and
      quantitative determination of antibodies (IgG) against varicella was performed
      using an ELISA assay with high sensitivity and specificity. RESULTS: 1,470
      samples were analyzed. After the decrease of seropositivity associated with the
      decay of passively acquired antibody titer, there was a progressive increase of
      seroprevalence in the other age groups. The comparison with what was recorded in
      two studies conducted with similar assays in the periods 1996/97 and 2003/04,
      showed a significant increase in seroprevalence following extensive immunization,
      particularly in the age classes 1 year, 2-4 years and 5-9 years. The proportion
      of seropositivity in the age classes 1 year and 2-4 years has more than doubled.
      CONCLUSIONS: Seroepidemiological studies are a useful tool to evaluate the
      distribution of susceptible individuals in the population. This study highlighted
      the impact of extensive vaccination against varicella in eight "pilot" Regions.

PMID- 25759346
TI  - [Legionella spp. contamination in indoor air: preliminary results of an Italian
      multicenter study].
AB  - OBJECTIVE: To propose a standardized protocol for the evaluation of Legionella
      contamination in air. DESIGN: A bathroom having a Legionella contamination in
      water >1,000 cfu/l was selected in 10 different healthcare facilities. Air
      contamination was assessed by active (Surface Air System, SAS) and passive (Index
      of Microbial Air, IMA) sampling for 8 hours, about 1 m away from the floor and 50
      cm from the tap water. Two hundred liters of air were sampled by SAS every 12
      min, after flushing water for 2 min. The IMA value was calculated as the mean
      value of colony forming units/16 plates exposed during sampling (2 plates/hour).
      Water contamination was evaluated at T0, after 4 and 8 hours, according to the
      standard methods. RESULTS: Air contamination by Legionella was found in three
      healthcare facilities (one with active and two with passive sampling), showing a
      concomitant tap water contamination (median=40,000; range 1,100-43,000 cfu/l).
      The remaining seven hospitals isolated Legionella spp. exclusively from water
      samples (median=8,000; range 1,200-70,000 cfu/l). CONCLUSIONS: Our data suggest
      that environmental Legionella contamination cannot be assessed only through the
      air sampling, even in the presence of an important water contamination.

PMID- 25759347
TI  - [Immunization campaign with 13-valent Pneumococcal Conjugate Vaccine in adults in
      Liguria Region, Italy: one year post-introduction preliminary results].
AB  - OBJECTIVE: To assess the impact of the immunization program with 13-valent
      Pneumococcal Conjugate Vaccine (PCV13) in adults, from October 2013 in Liguria,
      Italy, both in terms of effectiveness, and tolerability and safety. METHODS:
      First study: descriptive epidemiology of the clinical burden of lower respiratory
      tract infections (LRTI) and the role of risk factors or co-morbidity in adults
      >18 years of age. Second study: crossover evaluation of the effect of PCV13
      introduction in adults aged >=70 years, in terms of ED accesses for LRTI,
      obtained by a Syndrome Surveillance System (SSS) operating in Liguria from 2007.
      Third study: evaluation of safety and tolerability profile of PCV13 in terms of
      local and systemic solicited and unsolicited adverse events. RESULTS: During pre
      PCV period, annual cumulative incidence of ED accesses for LRTI was equal to
      7/1000 and 2% in >=65 and >=85 year adults, respectively. In >=65 years adults,
      more than 70% of identified subjects has at least one risk condition. A
      significant reduction in the incidence of ED accesses for LRTI in the vaccinated
      population, compared to non-vaccinated subjects, has already been observed: the
      preventive fraction, adjusted for age and seasonality, was estimated to be nearly
      20%. PCV13 had a good safety and tolerability profile: rates of local (32%) and
      systemic (22%) solicited reactions resulted generally lower than those registered
      in clinical trials previously performed in the elderly. CONCLUSIONS: Preliminary
      PCV13 assessments regarding safety and tolerability profile, together with the
      initial effects of the immunization program in terms of reduction of ED accesses
      for LRTI, confirmed the effectiveness of current Liguria Region recommendations
      for the prevention of pneumococcal disease in adult population.

PMID- 25759348
TI  - [Cardiovascular screening].
AB  - OBJECTIVE: To evaluate, through active call, lifestyles of an asymptomatic
      population in order to identify hyperglycaemic subjects and/or high-blood
      pressure sufferers to dispatch to their GP to perform suitable checking, and
      subjects to invite to a cardiovascular disease prevention programme because of
      their lifestyles. SETTING AND PARTICIPANTS: Between April 2011 and March 2013,
      all healthy residents in 6 Local Health Authorities of Regione Veneto aged 45-59
      years were invited to join a cardiovascular disease prevention programme. DESIGN:
      All participants were evaluated through an administered lifestyle questionnaire.
      Parameters such as blood pressure (BP), glycemia, waist circumference and body
      mass index were collected and recorded. Participants also received counseling,
      informational materials on lifestyle and were invited to individual or group
      health promotion initiatives in relation to personal risk factors. RESULTS: Among
      the invited, 60.84%(10,346/17,004) adhered. Subjects without risks factors were
      23.95%. Subjects with lifestyle risk factors but normal BP and glycemia were
      56.59%, while those with altered values for BP and glycemia were 13.9%. The 5.55%
      of the respondents was not eligible for the study. CONCLUSIONS: The results
      confirmthat a preventive programme based on the citizens active call by the
      Department of prevention could be an effective tool to identify asymptomatic
      individuals with unknown hypertension and/or hyperglycaemia and to offer
      lifestyle interventions to lower the risk of cardiovascular diseases. Since the
      results were positive, the the Regional Veneto Centre for Disease Prevention and
      Control (CCMR - Veneto) presented a similar project to the Ministry of Health,
      involving 12 Italian Regions.

PMID- 25759349
TI  - [Health status of immigrants arrived to Italian coast].
AB  - OBJECTIVE: To analyze the factors involved in access to Emergency Department (ED)
      of undocumented immigrants in Lampedusa according to the country of origin.
      DESIGN: This is a retrospective observational study, carried out on newly arrived
      undocumented immigrants transferred to ED. SETTING AND PARTICIPANTS: Data were
      collected from medical records of Lampedusa ED between January 2012 and May 2013
      on 326 undocumented immigrants. MAIN OUTCOME MEASURES: The outcomes evaluated are
      demographics characteristics and health condition of undocumented immigrants.
      RESULTS: In multivariate analysis associated factors to ED visits are: other
      pathologies rather than traumatic diseases (OR 0.22; p <0.001), younger age (OR
      0.9; p <0.001) and female sex (OR 12.49; p=0.017) for Somalis;
      gastroenterological diseases (OR 2.55; p=0.026) and older age (OR 1.6; p=0.004)
      for Eritrean; neurological disease (OR 5.33; p=0.048) and male sex (OR 5.45;
      p=0.032) for Tunisian. CONCLUSION: This analysis shows that undocumented
      immigrants cannot be considered as a single population, because they generate a
      diversified set of pathological conditions.

PMID- 25759350
TI  - [Tuberculosis surveillance in Sicily, Italy].
AB  - OBJECTIVE: To describe the epidemiology of tuberculosis (TB) in Sicily in the
      years 2010-2013. DESIGN AND PARTICIPANTS: Observational study of the TB
      notifications in the years 2010-2013 by analyzing the Sistema informative delle
      malattie infettive (SIMI) database and carrying out a molecular epidemiological
      analysis by spoligo- e 24-loci mycobacterial interspersed repetitive units
      variable number of tandem repeats (MIRU-VNTR) typing of the Mycobacterium
      tuberculosis complex (MTBC) isolates identified in Palermo, Italy, in the years
      2012-2013. RESULTS: In the four-year period under study 876 TB cases were
      notified in Sicily with a mean annual notification rate of 4.4 cases per 100,000
      inhabitants. The proportion of TB cases in the foreign-born individuals was
      increasing and higher than the proportion in Italian-born in the period 2010
      2013. The median age of foreign-born patients was significantly lower than the
      Italian-born (30.5 vs. 51.2 years, p <0,001). Moreover, the distribution by age
      class was also significantly different, with the largest proportion of TB cases
      among the foreign-born sub-population in the 15-44 age class, whereas the Italian
      born cases were equally distributed in the 15-44, 45-64 and >64 age classes.
      Eighty-two percent of cases were pulmonary TB. Molecular typing of 151 MTBC
      isolates identified in Palermo in 2012 and 2013 detected14 lineages and 33
      subline ages showing a different distribution among the two patients sub
      populations. Only nine MTBC isolates (6.2%) were grouped in four clusters. Two
      multidrug resistant (MDR) MTBC isolates were identified from an Italian born
      elderly patient and an Eritrean young patient (Beijing lineage), respectively.
      CONCLUSIONS: TB epidemiology in Sicily is complex and is rapidly changing. The
      most striking features are the increasing proportion of cases in the foreign-born
      population and the wide heterogeneity of MTBC isolates. An integrated approach
      using both conventional and molecular tools is necessary to accurately assess and
      monitor TB epidemiology in this Region.

PMID- 25759351
TI  - [Human Papillomavirus infection and vaccination: knowledge and attitudes of
      Italian general practitioners].
AB  - OBJECTIVE: To assess General Pratictioner's (GPs) knowledge and attitudes about
      HPV infection and prevention. DESIGN AND PARTICIPANTS: A semi-structured survey
      was conducted from November to December 2013 among Italian GPs. Descriptive and
      univariate analyses were carried out. MAIN OUTCOME MEASURES AND RESULTS: 938 GPs
      were included in the study. 15% participated in continuing medical education
      courses focusing on HPV. GPs identified as HPV transmission routes: sexual
      (100%), cutaneous (15%), transplacental (13%), haematic (9%) and by air (2%);
      they considered HPV-related diseases: cervical (98%), vulvar and vaginal (42%),
      anal (39%), penile (38%) and oral (38%) cancer, genital warts (79%) and
      respiratory papillomatosis (12%). They knew HPV vaccination is to prevent HPV
      associated cancer (60%), in particular cervical cancer (35%), genital warts (3%)
      and sexually transmitted diseases (2%). A total of 73% were aware of the
      existence of both available vaccines, 69% believed that immunization target
      population should be females before initiation of sexual activity, 87% knew the
      age of vaccine administration. No significant difference in knowledge was
      retrieved by age, gender, level of education or region of origin. CONCLUSION: We
      report a lack of knowledge on HPV infection and vaccination in GPs. GPs have a
      key role in the Italian health system. Although 12-year old patients are a small
      percentage of their patients, it is of fundamental importance to promote medical
      education and training among GPs in order to meet HPV coverage targets and
      control HPV-associated diseases.

PMID- 25759352
TI  - [Point prevalence survey of health care associated infections and antimicrobial
      use in Piedmont Region long-term care facilities according to ECDC protocol].
AB  - OBJECTIVE: Aim of this study is to examine the prevalence data from different
      types of long-term care facilities (LTCFs); we also analyzed similarities and
      differences between them and national data. DESIGN: "Healthcare-Associated
      Infections and Antimicrobial Use in European Long-Term Care Facilities Project"
      (HALT2) is a prevalence survey of health care associated infections and
      antimicrobial use in European long-term care facilities. The study protocol is
      developed, funded and promoted by the ECDC (European Centre for Disease
      Prevention and Control). SETTING AND PARTICIPANTS: Data were collected on a
      single day from long term care facilities (LTCFs) defined as facilities in which
      residents need constant supervision (24 hours). Two types of questionnaires had
      to be completed. MAIN OUTCOME MEASURES: Point prevalence of healthcare-associated
      infections (HAI) and antimicrobial use (AU). RESULTS: 63 LTCFs in Piedmont Region
      participated in the HALT-2 point prevalence survey; 3,984 residents met the
      eligibility criteria. The crude prevalence of residents with at least one HAI was
      3% in LTCF and 10% in CA/DP facilities. The crude prevalence of residents
      receiving at least one antimicrobial agent was 4%; this percentage rose to 17.4 %
      in CA/DP facilities. CONCLUSIONS: Data from Piedmont Region are similar to
      national data; differences are highlighted in different types of LTCFs. The
      results show the need to improve antimicrobial stewardship and to define
      protocols in each type of facilities in order to standardize the appropriateness
      and patient management.

PMID- 25759353
TI  - [Polio vaccination failure in Italy, years 2006-2010].
AB  - OBJECTIVE: The purpose of this paper is to describe the lack of antipolio
      vaccination and its reasons, in the period 2006-2010. STUDY DESIGN, SETTING AND
      PARTICIPANTS. Until 2014 the data on vaccination activities, aggregated at the
      regional level, were sent to the Ministry of Health using a paper form used to
      collect the data and then to calculate vaccine coverage (CV) at 24 months. This
      form contains a section for identifying the reasons for polio vaccination
      failure. RESULTS: During the reporting period the national CV was always above
      95%. The highest rates of non-vaccination were always observed in the same
      Region. Polio vaccination failure is well explained in 82%of cases, but only
      three Regions have always provided an explanation, while two have extremely low
      percentages of explanation, less than 50%. The dominant mode is "noncompliant "
      (45.5%), followed by "undetectable" (26.5%). CONCLUSIONS: The percentage of
      explanation of non-vaccination was lower than expected. At the moment we cannot
      clarify why, but only speculate that the lack of a computerized immunization
      registry has been a key element. Probably, the form used was not sufficiently
      detailed to monitor the phenomenon of non-vaccination and program interventions.
      Updating the form, in 2013, we took into account these and other critical issues.

PMID- 25759354
TI  - [The planning of prevention in Italy: the perspective of the university].
AB  - OBJECTIVE: The Department of Public Health and Infectious Diseases of Sapienza
      University of Rome conducted a critical appraisal of Regional Prevention Plans
      (RPPs) 2010-2012 aimed at exploring different quality elements of the RPPs,
      including the coherence with the epidemiological context and with regional health
      planning, the degree of attention to specific public health issues, the adherence
      to the principles of Project Cycle Management (PCM) and Evidence-Based Prevention
      (EBP), as well as at analyzing possible determinants of the quality of RPPs, such
      as the influence of Recovery Plans. METHODS: A grid analysis evidence-based was
      use to conduct, for the two RPPs areas (i.e. strategic and operative planning):
      1. the descriptive analysis of RPPs; 2. the analysis of the projects included in
      RPPs. RESULTS: The analysis showed some strengths and weaknesses in the
      prevention planning process, including a low adherence to the principles of EBP
      and a low degree of attention towards the reduction of health inequalities.
      Furthermore, projects developed by Regions with recovery plans showed a lower
      quality. CONCLUSIONS: The role of the University in the ongoing evaluation of the
      planning process, but also in monitoring the health status of the population,
      with particular attention to regional differences, can be crucial to support
      regional capacity building in prevention planning.

PMID- 25759355
TI  - [Residency in hygiene and preventive medicine: present and future].
AB  - INTRODUCTION: The changing needs and expectations of the population and the
      current financial distress lead the Italian health care system to face a profound
      challenge that requires also a new evaluation of professionals' training.
      Specialists in Hygiene and Preventive Medicine (HPM) are called for to develop
      new knowledge and skills in hygiene, public health, and management, as they
      fulfill leadership roles within the hospitals. OBJECTIVE: To investigate the
      current status of Hospital Health Management Boards (HHMB) and the specific know
      how they require, in order to develop an adequate post-graduate residency
      training in HPM. MATERIALS AND METHODS: We conducted a literature review on the
      main and "gray literature" databases; then, we conducted three semi-structured
      interviews with the Chiefs of the HHMB operating in the major hospitals of
      Bologna (Northern Italy); lastly, we organised a workshop with residents in HPM
      and health workers of Emilia-Romagna hospitals. RESULTS: Interviews with Hospital
      Health Managers have highlighted the main issues faced by a modern HHMB. The main
      questions discussed were: the changing role of the hospital and its relationship
      with primary care; the increasing competition among professionals with different
      specialisations within the HHMB; the need to develop multi-professional teams;
      the necessity to enlarge HPM residency training programmes in order to meet the
      HHMB needs. CONCLUSION: The evolution of the HHMB reflects the evolution of the
      Italian health care system. HHMBs should better fit the organization to the
      context, and the post-graduate schools in HPM should follow this process. In the
      framework of the current rules and laws it is possible to focus for implementing
      training programmes that include management, coordination and negotiation skills,
      and help build an adequate leadership profile.

PMID- 25759356
TI  - [The key role of public health medical resident education for future public
      health challenges].
AB  - INTRODUCTION: The Italian Committee of medical residents in Hygiene, Preventive
      Medicine and Public Health is a member of the Italian Society of Hygiene,
      Preventive Medicine and Public Health with the aim of developing a network among
      Italian resident in public health and promoting the educational path improvement
      through comparisons and debates between postgraduate medical schools. In this
      perspective, during last years account has been taken of some essential topics
      concerning education of public health medical residents, which represent future
      health-care and public health experts. METHODS: Cross-sectional researches were
      conducted among Italian public health medical residents (PHMRs) through self
      administered and web-based questionnaires. Each questionnaire was previously
      validated by pilot studies conducted during the 46th National Conference of the
      Italian Society of Hygiene, Preventive Medicine and Public Health. RESULTS:
      Seventy percent of Italian PHMRs considered the actual length of Public Health
      postgraduate medical school excessively long, with regard to predetermined
      educational goals. Confirming this statement, 90% of respondents were inclined to
      a reduction from 5 to 4 years of postgraduate medical school length, established
      by Law Decree 104/2013. Seventy seven percent of surveyed PHMRs stand up for a
      rearrangement on a national setting of the access contest to postgraduate medical
      schools. Moreover 1/3 of Italian schools performed less than 75%of learning and
      qualifying activities specified in Ministerial Decree of August 2005. In
      particular, data analysis showed considerable differences among Italian
      postgraduate schools. Finally, in 2015 only four Italian Universities (Napoli
      Federico II, Palermo, Pavia, Roma Tor Vergata) provide for the Second Level
      Master qualify for the functions of occupational doctor. This offer makes
      available 60 positions against a request of over 200 future Public Health medical
      doctors who have shown interest in the Master. CONCLUSIONS: In Italy, after the
      introduction of Ministerial Decree 285/2005, the educational course of PHMRs was
      significantly improved. The standardization of learning and qualifying activities
      allowed for the first time the attendance at medical directions or Local Health
      Units. Nevertheless, the excessive lenght of postgradute schools and the
      differences about training among Italian Universities are critical and actual
      issue. Moreover, the remarkable interest shown by PHMRs in the Master could
      suggest a poor job replacement prospect for young medical specialist in Hygiene,
      Preventive Medicine and Public Health.

PMID- 25759357
TI  - [How to fight anti-vaccinists prejudices: the viewpoint of public health].
AB  - Over the last two decades, growing numbers of parents in the industrialized world
      are choosing not to have their children vaccinated. The re-emergence of the anti
      vaccination movements has been theorized as an important determinant of this
      phenomenon. The crisis of the "vaccination system" and the resurgence of the anti
      vaccination movements is related both, to the increased accessibility to the
      information from the general population and to the decreased credibility and
      authority of health professionals. Another critical element in the fight against
      anti-vaccination movements, in Italy, is the system of assessing the damage from
      the vaccine, both in pharmacovigilance activities and in the procedures for the
      compensation of biological damage provided by law. The contrast in these bugs,
      along with the strengthening of communication skills of the health care workers
      and to an investment on communication in the mass media, is not to postpone for
      fighting the anti-vaccination movements. 

PMID- 25759358
TI  - [The ideation of the Emilia-Romagna surveillance system for arbovirosis following
      the experience from the Chikungunya outbreak 2007].
AB  - Since 2008 the Emilia-Romagna Regional public health authority activated a
      regional Plan for arbovirosis surveillance and control, focused on Chikungunya,
      Dengue and West Nile. The Plan integrates sanitary, entomological and veterinary
      surveillance allowing a prompt adoption of efficient measures, aiming at the
      prevention and reduction of arbovirosis transmission risk. Following the 2007
      Chikungunya outbreak, no autochthonous Chikungunya or Dengue cases has been
      registered, while an increase of confirmed imported cases of Dengue and
      Chikungunya has been observed. The integrated surveillance system allowed a
      prompt, appropriate and efficient intervention in 98.2% of imported suspected
      cases. The humanWNND (West Nile Neuroinvasive Disease) surveillance reported
      confirmed cases in 2008, 2009 and then in 2013 and 2014. In all cases the
      entomological and ornithological surveillance detected WNV circulation well in
      advance respect to the appearance of the first human case. The integration of
      information provided by different surveillance sources allows to evaluate, even
      through the vector index (VI) calculation, the risk of transmission, to optimize
      preventive measures on blood, tissues and organs donation and to implement
      further measures of vector fight. 

PMID- 25759359
TI  - [The 2014 lifetime immunization schedule approved by the Italian scientific
      societies. Italian Society of Hygiene, Preventive Medicine, and Public Health.
      Italian Society of Pediatrics. Italian Federation of Pediatric Physicians.
      Italian Federation of General Medical Physicians. Arezzo Service of Legal
      Medicine].

PMID- 25759360
TI  - [Pneumococcal vaccination in adults: recommendations from the Italian Society of
      Respiratory Medicine (SIMeR) and the Italian Society of Hygiene, Preventive
      Medicine and Public Health (SItI)].

PMID- 25759361
TI  - [Education and training in patient safety and prevention and control of
      healthcare associated infections].

PMID- 25759363
TI  - From the principles of genomic data sharing to the practices of data access
      committees.
AB  - Sharing genomic research data through controlled-access databases has increased
      in recent years. Policymakers and funding organizations endorse genomic data
      sharing in order to optimize the use of public funds and to increase the
      statistical power of databases. Well-established data access arrangements and
      data access committees (DACs)-responsible for reviewing and managing requests for
      access to genomic databases-are therefore central for implementing the policies
      and principles of data sharing. This article aims to investigate the
      functionality of DACs through the perspective of existing practices.

PMID- 25759362
TI  - A DNA/HDAC dual-targeting drug CY190602 with significantly enhanced anticancer
      potency.
AB  - Genotoxic drugs constitute a major treatment modality for human cancers; however,
      cancer cells' intrinsic DNA repair capability often increases the threshold of
      lethality and renders these drugs ineffective. The emerging roles of HDACs in DNA
      repair provide new opportunities for improving traditional genotoxic drugs. Here,
      we report the development and characterization of CY190602, a novel bendamustine
      derived drug with significantly enhanced anticancer potency. We show that
      CY190602's enhanced potency can be attributed to its newly gained ability to
      inhibit HDACs. Using this novel DNA/HDAC dual-targeting drug as a tool, we
      further explored HDAC's role in DNA repair. We found that HDAC activities are
      essential for the expression of several genes involved in DNA synthesis and
      repair, including TYMS, Tip60, CBP, EP300, and MSL1. Importantly, CY190602, the
      first-in-class example of such DNA/HDAC dual-targeting drugs, exhibited
      significantly enhanced anticancer activity in vitro and in vivo. These findings
      provide rationales for incorporating HDAC inhibitory moieties into genotoxic
      drugs, so as to overcome the repair capacity of cancer cells. Systematic
      development of similar DNA/HDAC dual-targeting drugs may represent a novel
      opportunity for improving cancer therapy.

PMID- 25759364
TI  - Combined Nurr1 and Foxa2 roles in the therapy of Parkinson's disease.
AB  - Use of the physiological mechanisms promoting midbrain DA (mDA) neuron survival
      seems an appropriate option for developing treatments for Parkinson's disease
      (PD). mDA neurons are specifically marked by expression of the transcription
      factors Nurr1 and Foxa2. We show herein that Nurr1 and Foxa2 interact to protect
      mDA neurons against various toxic insults, but their expression is lost during
      aging and degenerative processes. In addition to their proposed cell-autonomous
      actions in mDA neurons, forced expression of these factors in neighboring glia
      synergistically protects degenerating mDA neurons in a paracrine mode. As a
      consequence of these bimodal actions, adeno-associated virus (AAV)-mediated gene
      delivery of Nurr1 and Foxa2 in a PD mouse model markedly protected mDA neurons
      and motor behaviors associated with nigrostriatal DA neurotransmission. The
      effects of the combined gene delivery were dramatic, highly reproducible, and
      sustained for at least 1 year, suggesting that expression of these factors is a
      promising approach in PD therapy.

PMID- 25759366
TI  - Exploring the Use of Special Housing Units by Men Released From New York
      Correctional Facilities: A Small Mixed-Methods Study.
AB  - This small, mixed-methods study sought to understand the use of special housing
      units among formerly incarcerated men. In the present study, 110 participants
      were placed in solitary confinement, ranging from <=30 days to 20 years, with a
      mean of 2 years (SD = 2.55). These men ranged in age from 35 to 67 years, with a
      mean age of 46 years. Years of incarceration ranged from less than 30 days to 34
      years; the mean number of years incarcerated was 4 (SD = 6.39). Of the 110
      participants, qualitative interviews were conducted with 30 men to explore their
      experiences during time spent in solitary. The qualitative themes that emerged
      from the study were getting special housing units might be used for punishment,
      getting used to solitary, and getting solitary might mean peace of mind.
      Personalized reentry plans for men placed in special housing units facilities are
      urgently needed.

PMID- 25759367
TI  - Precision medicine initiative.

PMID- 25759365
TI  - Antisense-mediated exon skipping: a therapeutic strategy for titin-based dilated
      cardiomyopathy.
AB  - Frameshift mutations in the TTN gene encoding titin are a major cause for
      inherited forms of dilated cardiomyopathy (DCM), a heart disease characterized by
      ventricular dilatation, systolic dysfunction, and progressive heart failure. To
      date, there are no specific treatment options for DCM patients but heart
      transplantation. Here, we show the beneficial potential of reframing titin
      transcripts by antisense oligonucleotide (AON)-mediated exon skipping in human
      and murine models of DCM carrying a previously identified autosomal-dominant
      frameshift mutation in titin exon 326. Correction of TTN reading frame in patient
      specific cardiomyocytes derived from induced pluripotent stem cells rescued
      defective myofibril assembly and stability and normalized the sarcomeric protein
      expression. AON treatment in Ttn knock-in mice improved sarcomere formation and
      contractile performance in homozygous embryos and prevented the development of
      the DCM phenotype in heterozygous animals. These results demonstrate that
      disruption of the titin reading frame due to a truncating DCM mutation can be
      restored by exon skipping in both patient cardiomyocytes in vitro and mouse heart
      in vivo, indicating RNA-based strategies as a potential treatment option for DCM.

PMID- 25759368
TI  - Do Men Know Which Lower Bowel Symptoms Warrant Medical Attention? A Web-Based
      Video Vignette Survey of Men in Western Australia.
AB  - The current study aims to explor how men would advise other men about seeking
      help for lower bowel symptoms and also to determine the factors that may
      influence help seeking. A purposive sample of Western Australian men aged 18
      years and older was recruited for the study. Participants completed 8 of the 28
      randomly assigned video vignettes (video clips) displaying men (older or younger)
      with various combinations of one or more lower bowel symptoms. Participants were
      asked if the person in the vignette should seek health advice. Subsequently, the
      participants answered a set of questions based on the Health Belief Model. A
      total of 408 participants (response rate = 51%) answered 3,264 vignettes.
      Participants younger than 50 years, participants who were not tertiary educated
      and those who had lower incomes, or those living in regional or remote areas were
      less likely to advise help seeking from general practitioner (GP). Participants
      who visited their general practitioner less frequently were also less likely to
      advisehelp seeking. There was a trend to consider unintentional weight loss and
      diarrhea as minor symptoms not necessitating medical attention compared with
      rectal bleeding. The findings suggest for a need to improve public awareness
      among men about the need to seek timely medical advice for lower bowel symptoms
      in primary care. The importance of early presentation of persistent lower bowel
      symptoms must be specifically targeted at men younger than 50 years, those with
      lower incomes, or residing in regional or remote areas.

PMID- 25759369
TI  - Maternal Age and Contractility of Human Myometrium in Pregnancy.
AB  - There is controversy as to whether maternal age exerts an influence on the
      contractility of human myometrium in pregnancy. The aim of this study was to
      examine a series of functional contractile parameters of human myometrium in
      vitro, over a broad range of maternal ages. Myometrial tissue specimens were
      obtained at cesarean delivery from 32 women with maternal ages ranging from 28 to
      52 years. Using in vitro recordings, a number of contractile parameters including
      maximal amplitude, mean contractile force, time to maximal amplitude, maximum
      rate of rise, and occurrence of simple and complex (biphasic and multiphasic)
      contractions were examined for spontaneous and induced contractile activity. The
      relationship between maternal age and individual parameters was evaluated using
      linear regression analysis. For all contractile parameters examined, for both
      spontaneous and induced contractions, no significant correlation was observed
      with maternal age between 28 and 52 years. The mean maximum amplitude values for
      spontaneous and oxytocin-induced contractions were 23 +/- 3 and 43 +/- 5 mN,
      respectively. The mean contractile forces for spontaneous and oxytocin-induced
      contractions were 1.5 +/- 0.2 and 6.5 +/- 0.9 mN, respectively. There was no
      variation in the proportion of biphasic or multiphasic contractions with maternal
      age. These results indicate there is no significant functional impairment of
      uterine contractility and no lack in responsiveness of myometrium in vitro, in
      the older mother. These findings do not support the concept that there may be a
      biological basis for dysfunctional labor or increased cesarean delivery rates in
      older parturients. 

PMID- 25759370
TI  - Periostin Enhances Migration, Invasion, and Adhesion of Human Endometrial Stromal
      Cells Through Integrin-Linked Kinase 1/Akt Signaling Pathway.
AB  - Although our previous study confirmed that periostin (PN) was overexpressed in
      the eutopic and ectopic endometrial stroma of women with endometriosis by
      immunohistochemitry, the role of PN in the pathophysiology of endometriosis
      remains unknown. Thus, we aimed to investigate the effects of PN on endometrial
      stromal cells (ESCs) migration, invasion, adhesion, and proliferation and to
      further study the mechanism under this process. Eutopic (EuSCs), ectopic (EcSCs),
      and normal ESCs (NSCs) were isolated and cultured. We evaluated the above
      mentioned biology behaviors and the expression of PN, integrin-linked kinase 1
      (ILK1), and phospho-Akt (p-Akt) in NSCs, EuSCs as well as EcSCs before and after
      receiving PN small-interfering RNA (siRNA). The protein and messenger RNA (mRNA)
      levels of PN were upregulated in EuSCs (P < .05; P = .2261 in proliferative phase
      and P = .3385 in secretory phase) and EcSCs (P < .001; P < .001 in proliferative
      phase and P < .05 in secretory phase) compared with NSCs, although there was no
      significant difference in PN mRNA between EuSCs and NSCs. In EcSCs, abilities of
      migration, invasion, and adhesion and the expressions of ILK1 and p-Akt were
      enhanced; and all of those were downregulated after PN siRNA interference. Thus,
      PN enhanced ESCs migration, invasion, and adhesion due to the ILK1/Akt signal
      pathway. As an agonist in the development and progression of endometriosis, PN
      may be a new clinical treatment target of endometriosis. 

PMID- 25759371
TI  - Dielectric aggregation kinetics of cells in a uniform AC electric field.
AB  - BACKGROUND: Cell manipulation and separation technologies have potential
      biological and medical applications, including advanced clinical protocols such
      as tissue engineering. OBJECTIVE: An aggregation model was developed for a human
      carcinoma (HeLa) cell suspension exposed to a uniform AC electric field, in order
      to explore the field-induced structure formation and kinetics of cell aggregates.
      METHODS: The momentum equations of cells under the action of the dipole-dipole
      interaction were solved theoretically and the total time required to form linear
      string-like cluster was derived. The results were compared with those of a
      numerical simulation. Experiments using HeLa cells were also performed for
      comparison. RESULTS: The total time required to form linear string-like clusters
      was derived from a simple theoretical model of the cell cluster kinetics. The
      growth rates of the average string length of cell aggregates showed good
      agreement with those of the numerical simulation. In the experiment, cells were
      found to form massive clusters on the bottom of a chamber. The results imply that
      the string-like cluster grows rapidly by longitudinal attraction when the
      electric field is first applied and that this process slows at later times and is
      replaced by lateral coagulation of short strings. CONCLUSIONS: The findings
      presented here are expected to enable design of methods for the organization of
      three-dimensional (3D) cellular structures without the use of micro-fabricated
      substrates, such as 3D biopolymer scaffolds, to manipulate cells into spatial
      arrangement.

PMID- 25759372
TI  - Tragedy on Everest: the Khumbu icefall.

PMID- 25759374
TI  - When is it ok to tell patients they are overweight? General public's views of the
      role of doctors in supporting patients' dieting and weight management.
AB  - The objective was to explore the general public's views on the role of health
      professionals in the management of weight with diet and the implementation of
      behaviour change. Semi-structured interviews were conducted. An inductive
      grounded theory approach utilised a coding framework; recurring concepts/themes
      explored in future interviews and thematic saturation achieved. Two themes
      summarised views on the role of health professionals in supporting dieting and
      weight management: responsibility to initiate talk and what patients expect.
      Individuals perceive health professionals as having a role in their weight
      management. Individuals have disparate views about responsibility for initiation
      of weight management talk.

PMID- 25759375
TI  - Men, rheumatoid arthritis, psychosocial impact and self-management: A narrative
      review.
AB  - Rheumatoid arthritis is a chronic disease affecting fewer men than women. We
      systematically reviewed the literature on impact and self-management of
      rheumatoid arthritis in men. A total of 28 papers were included and grouped into
      two categories: psychosocial impact of rheumatoid arthritis, and coping and self
      management. This review finds gender differences relating to quality of life,
      work, distress, self-management, coping and support. We conclude that there is a
      dearth of literature focussing on rheumatoid arthritis in men only, and mixed
      gender studies include insufficient men to draw strong conclusions about men.
      Thus, further research is needed to understand the support needs of men with
      rheumatoid arthritis in depth.

PMID- 25759376
TI  - Danish nationwide registers for public health and health-related research.
AB  - AIMS: The Nordic countries have a strong tradition of using nationwide social and
      health registers for research purposes. The aim of the current paper is to
      provide an overview of the Danish population-based registers in public health and
      health-related research, and to discuss their strengths and limitations. METHODS:
      Danish registers on somatic and psychiatric hospital contacts as well as care
      provided by general practitioners were reviewed. The availability of demographic,
      individual-level variables of relevance for health-related research was
      summarized. RESULTS: Since 1968, every person living in Denmark has a unique
      identifier. This identifier is listed in Danish registers enabling linkage of
      information from a range of registers on an individual level. The nationwide
      coverage of all patient contacts at somatic and psychiatric hospitals,
      consultations with general practitioners, purchases of prescribed medications,
      and a complete follow-up with respect to causes of death support public health
      studies surveying trends of prevalence and incidence. Historical data on
      psychiatric and somatic hospitalizations since 1969 and 1977, respectively, allow
      an in-depth assessment of the burden of disease and time trends. Demographic
      characteristics of individuals and family units, together with information on
      education, employment, income, place of residence and migration, are provided by
      social registers. CONCLUSIONS: Register data are fully representative of the
      entire population with no loss to follow-up. Nationwide coverage also ensures a
      large sample to investigate events and conditions with low base rates. Clinical
      observations are limited and often only available for select patient populations.
      However, the opportunities available for public health research through linkage
      of register data with the increasing number of nationwide clinical databases, bio
      banks and surveys entail promising perspectives for future research.

PMID- 25759378
TI  - A common variant in the CLDN7/ELP5 locus predicts adiponectin change with
      lifestyle intervention and improved fitness in obese individuals with diabetes.
AB  - Overweight/obese individuals with Type 2 diabetes have low adiponectin levels,
      which may improve with lifestyle changes. We investigated whether genetic
      variants associated with adiponectin levels in genome-wide association studies
      (GWAS) would also be related with adiponectin changes in response to an intensive
      lifestyle intervention (ILI), potentially through mechanisms altering the adipose
      microenvironment via weight loss and/or improved cardiorespiratory fitness. Look
      AHEAD was a randomized trial comparing the cardiovascular benefits of ILI-induced
      weight loss and physical activity compared with diabetes support and education
      among overweight/obese individuals with Type 2 diabetes. In a subsample of Look
      AHEAD with adiponectin data and genetic consent (n=1,351), we evaluated the
      effects of 24 genetic variants, demonstrated by GWAS to be cross-sectionally
      associated with adiponectin, on adiponectin change 1-yr postintervention. We
      explored via mediational analyses whether any differential effects by treatment
      arm were occurring through weight loss and/or improved fitness. A variant,
      rs222857, in the CLDN7 locus, potentially associated with epithelial barrier
      integrity and tight junction physiology, and a putative cis expression
      quantitative trail locus for elongator acetyltransferase complex subunit 5
      (ELP5), predicted adiponectin increases within ILI (log-adiponectin in overall
      sample per copy: beta+/-SE=0.05+/-0.02, P=0.008; in non-Hispanic whites: 0.06+/
      0.02, P=0.009). The favorable effects of rs222857 (minor allele frequency 45.5%)
      appeared to be mediated by mechanisms associated with improved fitness, and not
      weight loss. This is the first study to identify a genetic variant that modifies
      adiponectin response to lifestyle intervention in overweight/obese diabetic
      individuals.

PMID- 25759377
TI  - Expression of three topologically distinct membrane proteins elicits unique
      stress response pathways in the yeast Saccharomyces cerevisiae.
AB  - Misfolded membrane proteins are retained in the endoplasmic reticulum (ER) and
      are subject to ER-associated degradation, which clears the secretory pathway of
      potentially toxic species. While the transcriptional response to environmental
      stressors has been extensively studied, limited data exist describing the
      cellular response to misfolded membrane proteins. To this end, we expressed and
      then compared the transcriptional profiles elicited by the synthesis of three ER
      retained, misfolded ion channels: The alpha-subunit of the epithelial sodium
      channel, ENaC, the cystic fibrosis transmembrane conductance regulator, CFTR, and
      an inwardly rectifying potassium channel, Kir2.1, which vary in their mass,
      membrane topologies, and quaternary structures. To examine transcriptional
      profiles in a null background, the proteins were expressed in yeast, which was
      previously used to examine the degradation requirements for each substrate.
      Surprisingly, the proteins failed to induce a canonical unfolded protein response
      or heat shock response, although messages encoding several cytosolic and ER
      lumenal protein folding factors rose when alphaENaC or CFTR was expressed. In
      contrast, the levels of these genes were unaltered by Kir2.1 expression; instead,
      the yeast iron regulon was activated. Nevertheless, a significant number of genes
      that respond to various environmental stressors were upregulated by all three
      substrates, and compared with previous microarray data we deduced the existence
      of a group of genes that reflect a novel misfolded membrane protein response.
      These data indicate that aberrant proteins in the ER elicit profound yet unique
      cellular responses. 

PMID- 25759379
TI  - Similarities and differences of X and Y chromosome homologous genes, SRY and
      SOX3, in regulating the renin-angiotensin system promoters.
AB  - The renin-angiotensin system (RAS) is subject to sex-specific modulation by
      hormones and gene products. However, sex differences in the balance between the
      vasoconstrictor/proliferative ACE/ANG II/AT1 axis, and the
      vasodilator/antiproliferative ACE2/ANG-(1-7)/MAS axis are poorly known. Data in
      the rat have suggested the male-specific Y-chromosome gene Sry to contribute to
      balance between these two axes, but why the testis-determining gene has these
      functions remains unknown. A combination of in silico genetic/protein
      comparisons, functional luciferase assays for promoters of the human RAS, and RNA
      Seq profiling in rat were used to address if regulation of Sry on the RAS is
      conserved in the homologous X-chromosome gene, Sox3. Both SRY and SOX3
      upregulated the promoter of Angiotensinogen (AGT) and downregulated the promoters
      of ACE2, AT2, and MAS, likely through overlapping mechanisms. The regulation by
      both SRY and SOX3 on the MAS promoter indicates a cis regulation through multiple
      SOX binding sites. The Renin (REN) promoter is upregulated by SRY and
      downregulated by SOX3, likely through trans and cis mechanisms, respectively. Sry
      transcripts are found in all analyzed male rat tissues including the kidney,
      while Sox3 transcripts are found only in the brain and testis, suggesting that
      the primary tissue for renin production (kidney) can only be regulated by SRY and
      not SOX3. These results suggest that SRY regulation of the RAS is partially
      shared with its X-chromosome homolog SOX3, but SRY gained a sex-specific control
      in the kidney for the rate-limiting step of the RAS, potentially resulting in
      male-specific blood pressure regulation. 

PMID- 25759380
TI  - FGFR1 and PROKR2 rare variants found in patients with combined pituitary hormone
      deficiencies.
AB  - The genetic aetiology of congenital hypopituitarism (CH) is not entirely
      elucidated. FGFR1 and PROKR2 loss-of-function mutations are classically involved
      in hypogonadotrophic hypogonadism (HH), however, due to the clinical and genetic
      overlap of HH and CH; these genes may also be involved in the pathogenesis of CH.
      Using a candidate gene approach, we screened 156 Brazilian patients with combined
      pituitary hormone deficiencies (CPHD) for loss-of-function mutations in FGFR1 and
      PROKR2. We identified three FGFR1 variants (p.Arg448Trp, p.Ser107Leu and
      p.Pro772Ser) in four unrelated patients (two males) and two PROKR2 variants
      (p.Arg85Cys and p.Arg248Glu) in two unrelated female patients. Five of the six
      patients harbouring the variants had a first-degree relative that was an
      unaffected carrier of it. Results of functional studies indicated that the new
      FGFR1 variant p.Arg448Trp is a loss-of-function variant, while p.Ser107Leu and
      p.Pro772Ser present signalling activity similar to the wild-type form. Regarding
      PROKR2 variants, results from previous functional studies indicated that
      p.Arg85Cys moderately compromises receptor signalling through both MAPK and Ca(2)
      (+) pathways while p.Arg248Glu decreases calcium mobilization but has normal MAPK
      activity. The presence of loss-of-function variants of FGFR1 and PROKR2 in our
      patients with CPHD is indicative of an adjuvant and/or modifier effect of these
      rare variants on the phenotype. The presence of the same variants in unaffected
      relatives implies that they cannot solely cause the phenotype. Other associated
      genetic and/or environmental modifiers may play a role in the aetiology of this
      condition. 

PMID- 25759381
TI  - Nuclear F-actin formation and reorganization upon cell spreading.
AB  - We recently discovered signal-regulated nuclear actin network assembly. However,
      in contrast to cytoplasmic actin regulation, polymeric nuclear actin structures
      and functions remain only poorly understood. Here we describe a novel molecular
      tool to visualize real-time nuclear actin dynamics by targeting the Actin
      Chromobody-TagGFP to the nucleus, thus establishing a nuclear Actin-Chromobody.
      Interestingly, we observe nuclear actin polymerization into dynamic filaments
      upon cell spreading and fibronectin stimulation, both of which appear to be
      triggered by integrin signaling. Furthermore, we show that nucleoskeletal
      proteins such as the LINC (linker of nucleoskeleton and cytoskeleton) complex and
      components of the nuclear lamina couple cell spreading or integrin activation by
      fibronectin to nuclear actin polymerization. Spreading-induced nuclear actin
      polymerization results in serum response factor (SRF)-mediated transcription
      through nuclear retention of myocardin-related transcription factor A (MRTF-A).
      Our results reveal a signaling pathway, which links integrin activation by
      extracellular matrix interaction to nuclear actin polymerization through the LINC
      complex, and therefore suggest a role for nuclear actin polymerization in the
      context of cellular adhesion and mechanosensing. 

PMID- 25759382
TI  - Sirtuin-3 (SIRT3) Protein Attenuates Doxorubicin-induced Oxidative Stress and
      Improves Mitochondrial Respiration in H9c2 Cardiomyocytes.
AB  - Doxorubicin (DOX) is a chemotherapeutic agent effective in the treatment of many
      cancers. However, cardiac dysfunction caused by DOX limits its clinical use. DOX
      is believed to be harmful to cardiomyocytes by interfering with the mitochondrial
      phospholipid cardiolipin and causing inefficient electron transfer resulting in
      the production of reactive oxygen species (ROS). Sirtuin-3 (SIRT3) is a class III
      lysine deacetylase that is localized to the mitochondria and regulates
      mitochondrial respiration and oxidative stress resistance enzymes such as
      superoxide dismutase-2 (SOD2). The purpose of this study was to determine whether
      SIRT3 prevents DOX-induced mitochondrial ROS production. Administration of DOX to
      mice suppressed cardiac SIRT3 expression, and DOX induced a dose-dependent
      decrease in SIRT3 and SOD2 expression in H9c2 cardiomyocytes. SIRT3-null mouse
      embryonic fibroblasts produced significantly more ROS in the presence of DOX
      compared with wild-type cells. Overexpression of wild-type SIRT3 increased
      cardiolipin levels and rescued mitochondrial respiration and SOD2 expression in
      DOX-treated H9c2 cardiomyocytes and attenuated the amount of ROS produced
      following DOX treatment. These effects were absent when a deacetylase-deficient
      SIRT3 was expressed in H9c2 cells. Our results suggest that overexpression of
      SIRT3 attenuates DOX-induced ROS production, and this may involve increased SOD2
      expression and improved mitochondrial bioenergetics. SIRT3 activation could be a
      potential therapy for DOX-induced cardiac dysfunction. 

PMID- 25759383
TI  - Cleavage Specificity of Mycobacterium tuberculosis ClpP1P2 Protease and
      Identification of Novel Peptide Substrates and Boronate Inhibitors with Anti
      bacterial Activity.
AB  - The ClpP1P2 protease complex is essential for viability in Mycobacteria
      tuberculosis and is an attractive drug target. Using a fluorogenic tripeptide
      library (Ac-X3X2X1-aminomethylcoumarin) and by determining specificity constants
      (kcat/Km), we show that ClpP1P2 prefers Met ? Leu > Phe > Ala in the X1 position,
      basic residues or Trp in the X2 position, and Pro ? Ala > Trp in the X3 position.
      We identified peptide substrates that are hydrolyzed up to 1000 times faster than
      the standard ClpP substrate. These positional preferences were consistent with
      cleavage sites in the protein GFPssrA by ClpXP1P2. Studies of ClpP1P2 with
      inactive ClpP1 or ClpP2 indicated that ClpP1 was responsible for nearly all the
      peptidase activity, whereas both ClpP1 and ClpP2 contributed to protein
      degradation. Substrate-based peptide boronates were synthesized that inhibit
      ClpP1P2 peptidase activity in the submicromolar range. Some of them inhibited the
      growth of Mtb cells in the low micromolar range indicating that cleavage
      specificity of Mtb ClpP1P2 can be used to design novel anti-bacterial agents. 

PMID- 25759384
TI  - The structure of the atypical killer cell immunoglobulin-like receptor, KIR2DL4.
AB  - The engagement of natural killer cell immunoglobulin-like receptors (KIRs) with
      their target ligands, human leukocyte antigen (HLA) molecules, is a critical
      component of innate immunity. Structurally, KIRs typically have either two (D1
      D2) or three (D0-D1-D2) extracellular immunoglobulin domains, with the D1 and D2
      domain recognizing the alpha1 and alpha2 helices of HLA, respectively, whereas
      the D0 domain of the KIR3DLs binds a loop region flanking the alpha1 helix of the
      HLA molecule. KIR2DL4 is distinct from other KIRs (except KIR2DL5) in that it
      does not contain a D1 domain and instead has a D0-D2 arrangement. Functionally,
      KIR2DL4 is also atypical in that, unlike all other KIRs, KIR2DL4 has both
      activating and inhibitory signaling domains. Here, we determined the 2.8 A
      crystal structure of the extracellular domains of KIR2DL4. Structurally, KIR2DL4
      is reminiscent of other KIR2DL receptors, with the D0 and D2 adopting the C2-type
      immunoglobulin fold arranged with an acute elbow angle. However, KIR2DL4 self
      associated via the D0 domain in a concentration-dependent manner and was observed
      as a tetramer in the crystal lattice by size exclusion chromatography, dynamic
      light scattering, analytical ultracentrifugation, and small angle x-ray
      scattering experiments. The assignment of residues in the D0 domain to forming
      the KIR2DL4 tetramer precludes an interaction with HLA akin to that observed for
      KIR3DL1. Accordingly, no interaction was observed to HLA by direct binding
      studies. Our data suggest that the unique functional properties of KIR2DL4 may be
      mediated by self-association of the receptor. 

PMID- 25759385
TI  - Membrane Anchoring by a C-terminal Tryptophan Enables HIV-1 Vpu to Displace Bone
      Marrow Stromal Antigen 2 (BST2) from Sites of Viral Assembly.
AB  - The restriction factor BST2 (tetherin) prevents the release of enveloped viruses
      from the host cell and is counteracted by HIV-1 Vpu. Vpu and BST2 interact
      directly via their transmembrane domains. This interaction enables Vpu to induce
      the surface down-regulation and the degradation of BST2, but neither of these
      activities fully accounts for the ability of Vpu to enhance virion release.
      During a study of naturally occurring Vpu proteins, we found that a tryptophan
      residue near the Vpu C terminus is particularly important for enhancing virion
      release. Vpu proteins with a W76G polymorphism degraded and down-regulated BST2
      from the cell surface, yet they inefficiently stimulated virion release. Here we
      explore the mechanism of this anomaly. We find that Trp-76 is critical for the
      ability of Vpu to displace BST2 from sites of viral assembly in the plane of the
      plasma membrane. This effect does not appear to involve a general reorganization
      of the membrane microdomains associated with virion assembly, but rather is a
      specific effect of Vpu on BST2. Using NMR spectroscopy, we find that the
      cytoplasmic domain of Vpu and Trp-76 specifically interact with lipids. Moreover,
      paramagnetic relaxation enhancement studies show that Trp-76 inserts into the
      lipid. These data are consistent with a model whereby Trp-76 anchors the C
      terminus of the cytoplasmic tail of Vpu to the plasma membrane, enabling the
      movement of Vpu-bound BST2 away from viral assembly sites. 

PMID- 25759386
TI  - PKD1 protein is involved in reactive oxygen species-mediated mitochondrial
      depolarization in cooperation with protein kinase Cdelta (PKCdelta).
AB  - In this study, we used gene targeting in mice to identify the in vivo functions
      of PKD1. In addition to phenotypically characterizing the resulting knock-out
      animals, we also used mouse embryonic fibroblasts to investigate the associated
      signaling pathways in detail. This study is the first to use genetic deletion to
      reveal that PKD1 is a key regulator involved in determining the threshold of
      mitochondrial depolarization that leads to the production of reactive oxygen
      species. In addition, we also provide clear evidence that PKCdelta is upstream of
      PKD1 in this process and acts as the activating kinase of PKD1. Therefore, our in
      vivo data indicate that PKD1 functions not only in the context of aging but also
      during nutrient deprivation, which occurs during specific phases of tumor growth.

PMID- 25759387
TI  - The Wnt Target Protein Peter Pan Defines a Novel p53-independent Nucleolar Stress
      Response Pathway.
AB  - Proper ribosome formation is a prerequisite for cell growth and proliferation.
      Failure of this process results in nucleolar stress and p53-mediated apoptosis.
      The Wnt target Peter Pan (PPAN) is required for 45 S rRNA maturation. So far, the
      role of PPAN in nucleolar stress response has remained elusive. We demonstrate
      that PPAN localizes to mitochondria in addition to its nucleolar localization and
      inhibits the mitochondrial apoptosis pathway in a p53-independent manner. Loss of
      PPAN induces BAX stabilization, depolarization of mitochondria, and release of
      cytochrome c, demonstrating its important role as an anti-apoptotic factor.
      Staurosporine-induced nucleolar stress and apoptosis disrupt nucleolar PPAN
      localization and induce its accumulation in the cytoplasm. This is accompanied by
      phosphorylation and subsequent cleavage of PPAN by caspases. Moreover, we show
      that PPAN is a novel interaction partner of the anti-apoptotic protein
      nucleophosmin (NPM). PPAN depletion induces NPM and upstream-binding factor (UBF)
      degradation, which is independent of caspases. In summary, we provide evidence
      for a novel nucleolar stress-response pathway involving PPAN, NPM, and BAX to
      guarantee cell survival in a p53-independent manner. 

PMID- 25759388
TI  - Heterotrimeric G proteins directly regulate MMP14/membrane type-1 matrix
      metalloprotease: a novel mechanism for GPCR-EGFR transactivation.
AB  - Agonist stimulation of G protein-coupled receptors (GPCRs) can transactivate
      epidermal growth factor receptors (EGFRs), but the precise mechanisms for this
      transactivation have not been defined. Key to this process is the protease
      mediated "shedding" of membrane-tethered ligands, which then activate EGFRs. The
      specific proteases and the events involved in GPCR-EGFR transactivation are not
      fully understood. We have tested the hypothesis that transactivation can occur by
      a membrane-delimited process: direct increase in the activity of membrane type-1
      matrix metalloprotease (MMP14, MT1-MMP) by heterotrimeric G proteins, and in
      turn, the generation of heparin-binding epidermal growth factor (HB-EGF) and
      activation of EGFR. Using membranes prepared from adult rat cardiac myocytes and
      fibroblasts, we found that MMP14 activity is increased by angiotensin II,
      phenylephrine, GTP, and guanosine 5'-O-[gamma-thio]triphosphate (GTPgammaS).
      MMP14 activation by GTPgammaS occurs in a concentration- and time-dependent
      manner, does not occur in response to GMP or adenosine 5'-[gamma
      thio]triphosphate (ATPgammaS), and is not blunted by inhibitors of Src, PKC,
      phospholipase C (PLC), PI3K, or soluble MMPs. This activation is specific to
      MMP14 as it is inhibited by a specific MMP14 peptide inhibitor and siRNA
      knockdown. MMP14 activation by GTPgammaS is pertussis toxin-sensitive. A role for
      heterotrimeric G protein betagamma subunits was shown by using the Gbetagamma
      inhibitor gallein and the direct activation of recombinant MMP14 by purified
      betagamma subunits. GTPgammaS-stimulated activation of MMP14 also results in
      membrane release of HB-EGF and the activation of EGFR. These results define a
      previously unrecognized, membrane-delimited mechanism for EGFR transactivation
      via direct G protein activation of MMP14 and identify MMP14 as a heterotrimeric G
      protein-regulated effector. 

PMID- 25759389
TI  - Vasodilator-stimulated phosphoprotein (VASP) regulates actin polymerization and
      contraction in airway smooth muscle by a vinculin-dependent mechanism.
AB  - Vasodilator-stimulated phosphoprotein (VASP) can catalyze actin polymerization by
      elongating actin filaments. The elongation mechanism involves VASP
      oligomerization and its binding to profilin, a G-actin chaperone. Actin
      polymerization is required for tension generation during the contraction of
      airway smooth muscle (ASM); however, the role of VASP in regulating actin
      dynamics in ASM is not known. We stimulated ASM cells and tissues with the
      contractile agonist acetylcholine (ACh) or the adenylyl cyclase activator,
      forskolin (FSK), a dilatory agent. ACh and FSK stimulated VASP Ser(157)
      phosphorylation by different kinases. Inhibition of VASP Ser(157) phosphorylation
      by expression of the mutant VASP S157A in ASM tissues suppressed VASP
      phosphorylation and membrane localization in response to ACh, and also inhibited
      contraction and actin polymerization. ACh but not FSK triggered the formation of
      VASP-VASP complexes as well as VASP-vinculin and VASP-profilin complexes at
      membrane sites. VASP-VASP complex formation and the interaction of VASP with
      vinculin and profilin were inhibited by expression of the inactive vinculin
      mutant, vinculin Y1065F, but VASP phosphorylation and membrane localization were
      unaffected. We conclude that VASP phosphorylation at Ser(157) mediates its
      localization at the membrane, but that VASP Ser(157) phosphorylation and membrane
      localization are not sufficient to activate its actin catalytic activity. The
      interaction of VASP with activated vinculin at membrane adhesion sites is a
      necessary prerequisite for VASP-mediated molecular processes necessary for actin
      polymerization. Our results show that VASP is a critical regulator of actin
      dynamics and tension generation during the contractile activation of ASM. 

PMID- 25759390
TI  - A pore-forming toxin requires a specific residue for its activity in membranes
      with particular physicochemical properties.
AB  - The physicochemical landscape of the bilayer modulates membrane protein function.
      Actinoporins are a family of potent hemolytic proteins from sea anemones acting
      at the membrane level. This family of cytolysins preferentially binds to target
      membranes containing sphingomyelin, where they form lytic pores giving rise to
      cell death. Although the cytolytic activity of the actinoporin fragaceatoxin C
      (FraC) is sensitive to vesicles made of various lipid compositions, it is far
      from clear how this toxin adjusts its mechanism of action to a broad range of
      physiochemical landscapes. Herein, we show that the conserved residue Phe-16 of
      FraC is critical for pore formation in cholesterol-rich membranes such as those
      of red blood cells. The interaction of a panel of muteins of Phe-16 with model
      membranes composed of raft-like lipid domains is inactivated in cholesterol-rich
      membranes but not in cholesterol-depleted membranes. These results indicate that
      actinoporins recognize different membrane environments, resulting in a wider
      repertoire of susceptible target membranes (and preys) for sea anemones. In
      addition, this study has unveiled promising candidates for the development of
      protein-based biosensors highly sensitive to the concentration of cholesterol
      within the membrane. 

PMID- 25759391
TI  - Myeloperoxidase-mediated Methionine Oxidation Promotes an Amyloidogenic Outcome
      for Apolipoprotein A-I.
AB  - High plasma levels of apolipoprotein A-I (apoA-I) correlate with cardiovascular
      health, whereas dysfunctional apoA-I is a cause of atherosclerosis. In the
      atherosclerotic plaques, amyloid deposition increases with aging. Notably, apoA-I
      is the main component of these amyloids. Recent studies identified high levels of
      oxidized lipid-free apoA-I in atherosclerotic plaques. Likely, myeloperoxidase
      (MPO) secreted by activated macrophages in atherosclerotic lesions is the
      promoter of such apoA-I oxidation. We hypothesized that apoA-I oxidation by MPO
      levels similar to those present in the artery walls in atherosclerosis can
      promote apoA-I structural changes and amyloid fibril formation. ApoA-I was
      exposed to exhaustive chemical (H2O2) oxidation or physiological levels of
      enzymatic (MPO) oxidation and incubated at 37  degrees C and pH 6.0 to induce
      fibril formation. Both chemically and enzymatically oxidized apoA-I produced
      fibrillar amyloids after a few hours of incubation. The amyloid fibrils were
      composed of full-length apoA-I with differential oxidation of the three
      methionines. Met to Leu apoA-I variants were used to establish the predominant
      role of oxidation of Met-86 and Met-148 in the fibril formation process.
      Importantly, a small amount of preformed apoA-I fibrils was able to seed amyloid
      formation in oxidized apoA-I at pH 7.0. In contrast to hereditary amyloidosis,
      wherein specific mutations of apoA-I cause protein destabilization and amyloid
      deposition, oxidative conditions similar to those promoted by local inflammation
      in atherosclerosis are sufficient to transform full-length wild-type apoA-I into
      an amyloidogenic protein. Thus, MPO-mediated oxidation may be implicated in the
      mechanism that leads to amyloid deposition in the atherosclerotic plaques in
      vivo. 

PMID- 25759393
TI  - Is organizational complexity the way to improve medical care? Unscientific
      reflections from going to the doctor in Cleveland and Paris.
AB  - Conventional wisdom suggests that health care will provide better value if
      physicians are replaced by other caregivers and care is provided less in "silos"
      and more in "integrated" organizations. By this standard French care appears
      backwards compared to American care. Yet that does not seem to make US care more
      efficient or effective. This perspective reviews some differences in practice and
      suggests why the conventional wisdom should be tested with research. 

PMID- 25759392
TI  - Cellular Models of Aggregation-dependent Template-directed Proteolysis to
      Characterize Tau Aggregation Inhibitors for Treatment of Alzheimer Disease.
AB  - Alzheimer disease (AD) is a degenerative tauopathy characterized by aggregation
      of Tau protein through the repeat domain to form intraneuronal paired helical
      filaments (PHFs). We report two cell models in which we control the inherent
      toxicity of the core Tau fragment. These models demonstrate the properties of
      prion-like recruitment of full-length Tau into an aggregation pathway in which
      template-directed, endogenous truncation propagates aggregation through the core
      Tau binding domain. We use these in combination with dissolution of native PHFs
      to quantify the activity of Tau aggregation inhibitors (TAIs). We report the
      synthesis of novel stable crystalline leucomethylthioninium salts (LMTX(r)),
      which overcome the pharmacokinetic limitations of methylthioninium chloride.
      LMTX(r), as either a dihydromesylate or a dihydrobromide salt, retains TAI
      activity in vitro and disrupts PHFs isolated from AD brain tissues at 0.16 MUM.
      The Ki value for intracellular TAI activity, which we have been able to determine
      for the first time, is 0.12 MUM. These values are close to the steady state
      trough brain concentration of methylthioninium ion (0.18 MUM) that is required to
      arrest progression of AD on clinical and imaging end points and the minimum brain
      concentration (0.13 MUM) required to reverse behavioral deficits and pathology in
      Tau transgenic mice.

PMID- 25759395
TI  - Depletion of suppressor of cytokine signaling-1a causes hepatic steatosis and
      insulin resistance in zebrafish.
AB  - Suppressor of cytokine signaling-1a (SOCS1a) is a member of the suppressor of
      cytokine signaling family, a group of related molecules that mediate the negative
      regulation of the JAK-STAT pathway. Here, we depleted SOCS1a using the
      transcription activator-like (TAL) effector nuclease (TALEN) technique to
      understand its physiological roles in zebrafish. Although elevated levels of JAK
      STAT5 activation and erythropoiesis have been observed in socs1a-deficient
      zebrafish, these animals exhibited normal growth during the early stages. Socs1a
      deficient zebrafish began to grow slowly with certain mortalities after 20 days
      postfertilization (dpf), whereas the heterozygous socs1a-deficient zebrafish
      exhibited enhanced somatic growth. Decreased adiposity, hepatic steatosis, and
      insulin resistance were observed in our socs1a-deficient adult zebrafish, which
      is similar to the lipodystrophy phenotypes observed in mammals. Comparative
      transcriptomic analyses revealed elevated levels of gluconeogenesis, lipolysis,
      and hypoxia-inducible response and decreased activities of lipogenesis and
      glycolysis in the hepatocytes of socs1a-deflicient adult zebrafish. Evident
      mitochondrial dysfunction has also been observed in hepatocytes from socs1a
      deficient zebrafish. Taken together, our results suggest that the negative
      regulatory roles of SOCS1a on JAK-STAT5 signaling may be involved in the
      suppression of the erythropoiesis and growth hormone activities, which was also
      reflected in the enhanced somatic growth performance observed in the heterozygous
      socs1a-deficient fish. The differences in the effects caused by SOCS1a depletion
      on insulin sensitivity, lipid metabolism, and inflammatory responses between
      zebrafish and mammalian models observed here may reflect differences between the
      functional mechanisms of SOCS members in terrestrial mammals and aquatic
      teleosts. 

PMID- 25759394
TI  - Dysregulation of skeletal muscle protein metabolism by alcohol.
AB  - Alcohol abuse, either by acute intoxication or prolonged excessive consumption,
      leads to pathological changes in many organs and tissues including skeletal
      muscle. As muscle protein serves not only a contractile function but also as a
      metabolic reserve for amino acids, which are used to support the energy needs of
      other tissues, its content is tightly regulated and dynamic. This review focuses
      on the etiology by which alcohol perturbs skeletal muscle protein balance and
      thereby over time produces muscle wasting and weakness. The preponderance of data
      suggest that alcohol primarily impairs global protein synthesis, under basal
      conditions as well as in response to several anabolic stimuli including growth
      factors, nutrients, and muscle contraction. This inhibitory effect of alcohol is
      mediated, at least in part, by a reduction in mTOR kinase activity via a
      mechanism that remains poorly defined but likely involves altered protein-protein
      interactions within mTOR complex 1. Furthermore, alcohol can exacerbate the
      decrement in mTOR and/or muscle protein synthesis present in other catabolic
      states. In contrast, alcohol-induced changes in muscle protein degradation,
      either global or via specific modulation of the ubiquitin-proteasome or autophagy
      pathways, are relatively inconsistent and may be model dependent. Herein, changes
      produced by acute intoxication versus chronic ingestion are contrasted in
      relation to skeletal muscle metabolism, and limitations as well as opportunities
      for future research are discussed. As the proportion of more economically
      developed countries ages and chronic illness becomes more prevalent, a better
      understanding of the etiology of biomedical consequences of alcohol use disorders
      is warranted.

PMID- 25759397
TI  - Absence of lactobacilli containing glycolipids with the alpha-galactose epitope
      and the enhanced fucosylation of a receptor glycolipid GA1 in the digestive
      tracts of immune-deficient scid mice.
AB  - The Lactobacillus species in the digestive tracts of immune-deficient scid mice
      was distinct from that in control mice, i.e. Lactobacillus murinus in scid and L.
      johnsonii in control mice, according to their 16S-rRNA, indicating that a
      symbiotic relationship between lactobacilli and a host is established under
      pressure from the immune system. The caecal and colonal contents rich in L.
      murinus of scid mice were loose with a strong sour smell, resulting in diarrhoea,
      and those with L. johnsonii in control mice included abundant solid materials.
      Lactobacillus glycolipids were revealed to be recognized by the immune system,
      and by TLC-immunostaining, LacTetH-DG (Galalpha1-6Galalpha1-6Galalpha1-2Glcalpha1
      3'DG) of L. johnsonii was detected in the stomach, caecum and colon of control
      mice, but not in those of scid ones, in which fucosylation of a receptor GA1 for
      L. johnsonii was enhanced more than 4-fold compared with in the control mice.
      Thus, structural modification of receptor glycolipids was revealed to occur in
      the process of establishment of a symbiotic relationship between lactobacilli and
      a host. LacTetH-DG was also immunogenic to human, because of the presence of
      natural antibodies against it, and the antibody binding to it was comparable to
      that of blood group- and species-related glycosphingolipids. 

PMID- 25759396
TI  - Transcription of Nrdp1 by the androgen receptor is regulated by nuclear filamin A
      in prostate cancer.
AB  - Prostate cancer (PCa) progression is regulated by the androgen receptor (AR);
      however, patients undergoing androgen-deprivation therapy (ADT) for disseminated
      PCa eventually develop castration-resistant PCa (CRPC). Results of previous
      studies indicated that AR, a transcription factor, occupies distinct genomic loci
      in CRPC compared with hormone-naive PCa; however, the cause of this distinction
      was unknown. The E3 ubiquitin ligase Nrdp1 is a model AR target modulated by
      androgens in hormone-naive PCa but not in CRPC. Using Nrdp1, we investigated how
      AR switches transcription programs during CRPC progression. The proximal Nrdp1
      promoter contains an androgen response element (ARE); we demonstrated AR binding
      to this ARE in androgen-sensitive PCa. Analysis of hormone-naive human
      prostatectomy specimens revealed correlation between Nrdp1 and AR expression,
      supporting AR regulation of NRDP1 levels in androgen-sensitive tissue. However,
      despite sustained AR levels, AR binding to the Nrdp1 promoter and Nrdp1
      expression were suppressed in CRPC. Elucidation of the suppression mechanism
      demonstrated correlation of NRDP1 levels with nuclear localization of the
      scaffolding protein filamin A (FLNA) which, as we previously showed, is itself
      repressed following ADT in many CRPC tumors. Restoration of nuclear FLNA in CRPC
      stimulated AR binding to Nrdp1 ARE, increased its transcription, and augmented
      NRDP1 protein expression and responsiveness to ADT, indicating that nuclear FLNA
      controls AR-mediated androgen-sensitive Nrdp1 transcription. Expression of other
      AR-regulated genes lost in CRPC was also re-established by nuclear FLNA. Thus,
      our results indicate that nuclear FLNA promotes androgen-dependent AR-regulated
      transcription in PCa, while loss of nuclear FLNA in CRPC alters the AR-regulated
      transcription program. 

PMID- 25759398
TI  - Detection of Changes in Surgical Difficulty: Evidence From Pupil Responses.
AB  - BACKGROUND: Assessing the workload of surgeons requires technology to
      continuously monitor surgeons' behaviors without interfering with their
      performance. We investigated the feasibility of using eye-tracking to reveal
      surgeons' response to increasing task difficulty. METHODS: A controlled study was
      conducted in a simulated operating room, where 14 subjects were required to
      perform a laparoscopic procedure that includes 9 subtasks. The subtasks could be
      divided into 3 types with different levels of task difficulty, calculated by the
      index of task difficulty (ID) proposed by Fitts in 1954. Pupillary responses of
      subjects in performing the procedure were recorded using Tobii eye-tracking
      equipment. Peak pupil dilation and movement time were compared between subtasks
      with different IDs as well as between fast moving and slow aiming phases within
      each subtask. RESULTS: When the task difficulty was increased, task completion
      time increased. Meanwhile, the subjects' peak pupil size also increased. As the
      entire procedure was performed continuously, we found that pupil responses were
      not only affected by the ID in the current subtask but also influenced by
      subtasks before and after. DISCUSSION: Decomposing a surgical procedure into
      meaningful subtasks and examining the surgeon's pupil response to each subtask
      enables us to identify the challenging steps within a continuous surgical
      procedure. Psychomotor evidence on surgeon's performance may lead to an
      innovation for designing a task-specific training curriculum.

PMID- 25759399
TI  - Antimicrobial Efficacy of a Historical High-Frequency Plasma Apparatus in
      Comparison With 2 Modern, Cold Atmospheric Pressure Plasma Devices.
AB  - BACKGROUND: Today, highly sophisticated devices deliver cold atmospheric pressure
      plasma (CAPP) with a multitude of bioactive properties, opening the window to a
      new medical field: plasma medicine. Different techniques to create the optimal
      plasma device for different medical indications are currently being explored.
      However, even a 100 years ago, CAPP was briefly used in the related form of high
      frequency therapy. The objective of our study was to compare historic with modern
      techniques regarding antimicrobial efficacy. METHODS: First, 26 different
      clinical isolates of relevant wound pathogens were treated in vitro with a
      historic violet wand (VW) and 2 modern plasma sources (kINPen 09 and dielectric
      barrier discharge [DBD]) and the obtained inhibition areas (IAs) were compared.
      Second, a biofilm model was used to compare biofilm inactivation by VW, DBD,
      ethanol, and polyhexanide treatment. RESULTS: DBD with the largest electrode
      produced the largest IAs. VW showed results similar to 2 different modes of the
      kINPen 09. IAs of VW were enlargeable by attaching a larger electrode. Against
      biofilms, VW was less effective than DBD but more effective than ethanol 70% and
      polyhexanide. CONCLUSION: The proven antimicrobial efficacy of VW may encourage
      the development of new, potent plasma devices based on the very simple and
      inexpensive technique of the historic high-frequency apparatus.

PMID- 25759401
TI  - Risk of emergency medical treatment following consumption of cannabis or
      synthetic cannabinoids in a large global sample.
AB  - BACKGROUND: Synthetic cannabinoids (SCs) have become increasingly popular in
      recent years. Diverse in chemical structure, many have been subjected to
      legislative regulation, but their availability and use persists. Often marketed
      to reflect their similar effects to cannabis, their use has been associated with
      a range of negative health effects. We sought to determine the relative risk of
      seeking emergency medical treatment (EMT) following use of SCs and natural
      cannabis. METHODS: We utilized an anonymous online survey of drug use, obtaining
      data from 22,289 respondents. We calculated the relative risk of seeking EMT
      between the two substances using an estimate for days used in the past year.
      RESULTS: Thirty-seven cannabis users (0.2%) and 21 SC users (1.0%) had sought EMT
      during the past year following use. The relative risk associated with the use of
      SCs was 30 (95% CI 17.5-51.2) times higher than that associated with cannabis.
      Significantly more symptoms (p=0.03) were reported by respondents seeking
      treatment for SCs than for cannabis. CONCLUSIONS: Whilst these findings must be
      treated with caution, SCs potentially pose a greater risk to users' health than
      natural forms of cannabis. Regulation is unlikely to remove SCs from the market,
      so well-informed user-focused health promotion messages need to be crafted to
      discourage their use.

PMID- 25759400
TI  - Early effects of duloxetine on emotion recognition in healthy volunteers.
AB  - The serotonin-noradrenaline reuptake inhibitor (SNRI) duloxetine is an effective
      treatment for major depression and generalised anxiety disorder.
      Neuropsychological models of antidepressant drug action suggest therapeutic
      effects might be mediated by the early correction of maladaptive biases in
      emotion processing, including the recognition of emotional expressions. Sub
      chronic administration of duloxetine (for two weeks) produces adaptive changes in
      neural circuitry implicated in emotion processing; however, its effects on
      emotional expression recognition are unknown. Forty healthy participants were
      randomised to receive either 14 days of duloxetine (60 mg/day, titrated from 30
      mg after three days) or matched placebo (with sham titration) in a double-blind,
      between-groups, repeated-measures design. On day 0 and day 14 participants
      completed a computerised emotional expression recognition task that measured
      sensitivity to the six primary emotions. Thirty-eight participants (19 per group)
      completed their course of tablets and were included in the analysis. Results
      provide evidence that duloxetine, compared to placebo, may reduce the accurate
      recognition of sadness. Drug effects were driven by changes in participants'
      ability to correctly detect subtle expressions of sadness, with greater change
      observed in the placebo relative to the duloxetine group. These effects occurred
      in the absence of changes in mood. Our preliminary findings require replication,
      but complement recent evidence that sadness recognition is a therapeutic target
      in major depression, and a mechanism through which SNRIs could resolve negative
      biases in emotion processing to achieve therapeutic effects. 

PMID- 25759402
TI  - Sleep is more sensitive to high doses of caffeine in the middle years of life.
AB  - During the middle years of life, sleep becomes more fragile and its sensitivity
      to psychostimulants may increase. This study evaluated the effects of 200 mg and
      400 mg of caffeine on sleep in young and middle-aged adults. The sleep of 22
      young (23.5 +/- 1.9 years) and 24 middle-aged (51.7 +/- 11.5 years) adults was
      recorded using polysomnography in two conditions (placebo and caffeine) in a
      double-blind cross-over design. Compared to placebo, caffeine increased sleep
      latency, shortened total sleep duration and reduced sleep efficiency. At the
      higher dose, these effects were more pronounced in middle-aged than in young
      adults. Furthermore, the higher dose of caffeine increased absolute stage 1 sleep
      in young adults, whereas it decreased absolute stage 2 sleep in middle-aged
      adults. Caffeine also induced dose-dependent increases in relative stage 1 sleep
      and reductions in absolute and relative slow wave sleep and absolute rapid eye
      movement sleep in both age groups. There was no dose- or age-related modulation
      of the effects of caffeine on quantified electroencephalographic measures. These
      results indicate that, compared to young adults, middle-aged adults are generally
      more sensitive to the effects of a high dose of caffeine on sleep quantity and
      quality. 

PMID- 25759404
TI  - Tianeptine in an experimental medicine model of antidepressant action.
AB  - Changes in emotional processing have been shown following acute administration of
      a range of monoaminergic antidepressants, and may represent an important common
      neuropsychological mechanism underpinning their therapeutic effects. Tianeptine
      is an agent that challenges the traditional monoaminergic hypothesis of
      antidepressant action, though its exact mode of action remains controversial.
      Healthy volunteers were randomised to receive a single dose of tianeptine (12.5
      mg) or placebo, and subsequently completed a battery of tasks measuring emotional
      processing, including facial expression recognition, emotional memory and
      attentional vigilance, as well as working and verbal memory. Tianeptine-treated
      subjects were less accurate at identifying facial expressions, though this was
      not valence specific. The tianeptine group also showed reduced positive affective
      memory and reduced attentional vigilance to positive stimuli. There were no
      effects on emotional categorization or non-emotional cognition. The negative
      biases in aspects of emotional processing observed following acute tianeptine
      administration are at variance with the positive biases generally seen after
      acute administration of conventional antidepressant drugs, despite tianeptine's
      putative antidepressant efficacy. This is an intriguing finding in the context of
      the lack of consensus regarding tianeptine's mechanism of action; however, it may
      be consistent with the reported ability of acute tianeptine to increase the re
      uptake of serotonin.

PMID- 25759403
TI  - Impact of subanesthetic doses of ketamine on AMPA-mediated responses in rats: An
      in vivo electrophysiological study on monoaminergic and glutamatergic neurons.
AB  - The rapid antidepressant action of a subanesthetic dose of ketamine in treatment
      resistant patients represents the most striking recent breakthrough in the
      understanding of the antidepressant response. Evidence demonstrates tight
      interactions between the glutamatergic and monoaminergic systems. It is thus
      hypothesized that monoamine systems may play a role in the immediate/rapid
      effects of ketamine. In vivo electrophysiological recordings were carried in male
      rats following ketamine administration (10 and 25 mg/kg, i.p.) to first assess
      its effects on monoaminergic neuron firing. In a second series of experiments,
      the effects of ketamine administration on alpha-amino-3-hydroxy-5-methyl-4
      isoxazolepropionic acid (AMPA)- and N-methyl-D-aspartate receptor (NMDA)-evoked
      responses in hippocampus CA3 pyramidal neurons were also investigated using micro
      iontophoretic applications. Although acute (~2 hours) ketamine administration did
      not affect the mean firing activity of dorsal raphe serotonin and ventral
      tegmental area dopamine neurons, it did increase that of locus coeruleus
      norepinephrine neurons. In the latter brain region, while ketamine also enhanced
      bursting activity, it did increase population activity of dopamine neurons in the
      ventral tegmental area. These effects of ketamine were prevented by the prior
      administration of the AMPA receptor antagonist 2,3-dioxo-6-nitro-1,2,3,4
      tetrahydrobenzo[f]quinoxaline-7-sulfonamide. An increase in AMPA-evoked response
      of CA3 pyramidal neurons was also observed 30 minutes following acute ketamine
      administration. The present findings suggest that acute ketamine administration
      produces a rapid enhancement of catecholaminergic neurons firing activity through
      an amplification of AMPA transmission. These effects may play a crucial role in
      the antidepressant effects of ketamine observed shortly following its infusion in
      depressed patients.

PMID- 25759405
TI  - A novel clonal t(1;4)(p36.1;q31) translocation in acute promyelocytic leukaemia.
AB  - The majority of patients with acute promyelocytic leukaemia (APL) carry the
      hallmark t(15;17)(q22;q21) translocation, involving the promyelocytic
      leukaemia/retinoic acid receptor-alpha (PML/RARalpha) fusion gene, and by
      sensitivity of blast cells to all-trans retinoic acid (ATRA) and/or arsenic
      trioxide therapy. The incidence and prognostic significance of additional
      chromosomal abnormalities in APL are still obscure. We reported a patient with
      APL with PML/RARalpha and clonal t(1;4)(p36.1;q31) positive, but
      t(15;17)(q22;q21) negative. She was initially treated with ATRA and idarubicin
      and got complete remission. Our report supports the suggestion that there are no
      differences in the clinical outcome between APL cases with classical
      t(15;17)(q22;q21) and those with additional chromosomal abnormality
      t(1;4)(p36.1;q31). To our knowledge, this is the first report of a patient with
      APL without classical t(15;17)(q22;q21), showing an additional clonal
      t(1;4)(p36.1;q31) and involving PML/RARalpha fusion gene. It will help us to
      understand the role of the clonal t(1;4)(p36.1;q31) translocation in the
      pathogenesis of APL when relevant genes involved in the clonal translocation have
      been identified.

PMID- 25759406
TI  - Combination of tumour markers CEA and CA19-9 improves the prognostic prediction
      in patients with pancreatic cancer.
AB  - AIMS: Tumour markers including carcinoembryonic antigen (CEA) or carbohydrate
      antigen 19-9 (CA19-9) are frequently determined at the time of diagnosis in
      patients with pancreatic cancer. Several studies indicate a prognostic relevance
      of these markers in pancreatic cancer, but space for improvement with regard to
      the predictive accuracy and ability is given. In this work, the main focus is on
      mathematical combinations of these two tumour markers in order to validate an
      improvement of prognostic test results in terms of sensitivity and specificity.
      METHODS: This retrospective study includes 393 patients with pancreatic cancer,
      who were treated between the years 2005 and 2012 at the Division of Oncology,
      Medical University of Graz, Austria. The goal of this study was to explore
      whether an appropriate combination of two tumour markers leads to a statistically
      significant improvement of the prognostic prediction. RESULTS: Receiver operating
      characteristic curves comparison analyses with the classification variable cancer
      specific survival showed that the mathematical product of two tumour markers
      (TM(product)= (CEA*CA19-9); area under the curve (AUC)=0.727; 95% CI 0.680 to
      0.770) is significantly better than CEA alone (AUC=0.644; 95% CI 0.594 to 0.691;
      p=0.003) but not significant compared with CA19-9 (AUC=0.710; 95% CI 0.662 to
      0.754; p=0.1215). A linear combination of CEA and CA19-9 (TM(linear)=(85*CEA+CA19
      9); AUC=0.748; 95% CI 0.702 to 0.790) is significantly better than CEA (p<0.0001)
      as well as CA19-9 alone (p=0.0304). CONCLUSIONS: Mathematical combinations of
      pretherapeutic tumour markers CEA and CA19-9 are feasible and can significantly
      improve the prognostic prediction in patients with pancreatic cancer.

PMID- 25759407
TI  - Does transcutaneous electrical nerve stimulation (TENS) alleviate the pain
      experienced during bone marrow sampling in addition to standard techniques? A
      randomised, double-blinded, controlled trial.
AB  - AIMS: Bone marrow aspiration and trephine (BMAT) biopsies remain important tests
      in haematology. However, the procedures can be moderately to severely painful
      despite standard methods of pain relief. To test the efficacy of transcutaneous
      electrical nerve stimulation (TENS) in alleviating the pain from BMAT in addition
      to standard analgesia using a numerical pain rating scale (NRS). METHODS: 70
      patients requiring BMAT were randomised (1:1) in a double-blind, placebo
      controlled trial. -35 patients received TENS impulses at a strong but comfortable
      amplitude (intervention group) and 35 patients received TENS impulses just above
      the sensory threshold (control group) (median pulse amplitude 20 and 7 mA,
      respectively). Patients and operators were blinded to group allocation. Pain
      assessments were made using a numerical pain scale completed after the procedure.
      RESULTS: No significant difference in NRS pain recalled after the procedure was
      detected (median pain score 5.7 (95% CI 4.8 to 6.6) in control vs 5.6 (95% CI 4.8
      to 6.4) in the intervention group). However, 100% of patients who had previous
      experience of BMAT and >94% of participants overall felt they benefited from
      using TENS and would recommend it to others for this procedure. There were no
      side effects from the TENS device, and it was well tolerated. CONCLUSIONS: TENS
      is a safe, non-invasive adjunct to analgesia for reducing pain during bone marrow
      biopsy and provides a subjective benefit to most users; however, no objective
      difference in pain scores was detected when using TENS in this randomised
      controlled study. CLINICAL REGISTRATION NUMBER: NCT02005354.

PMID- 25759408
TI  - Costs of unstructured investigation of unexplained syncope: insights from a micro
      costing analysis of the observational PICTURE registry.
AB  - AIMS: The observational PICTURE (Place of Reveal In the Care pathway and
      Treatment of patients with Unexplained Recurrent Syncope) registry enrolled 570
      patients with unexplained syncope, documented their care pathway and the various
      tests they underwent before the insertion of an implantable loop recorder (ILR).
      The aims were to describe the extent and cost of diagnostic tests performed
      before the implant. METHODS AND RESULTS: Actual costs of 17 predefined diagnostic
      tests were characterized based on a combination of data from PICTURE and a micro
      costing study performed at a medium-sized UK university hospital in the UK. The
      median cost of diagnostic tests per patient was L1114 (95% CI L995-L1233). As
      many patients received more than the median number of tests, the mean expenditure
      per patient was higher with L1613 (95% CI L1494-L1732), and for 10% of the
      patients the cost exceeded L3539. Tests were frequently repeated, and early use
      of specific and expensive tests was common. In the 12% of patients with types of
      tests entirely within the recommendations for an initial evaluation before ILR
      implant, the mean cost was L710. CONCLUSION: Important opportunities to reduce
      test-related costs before an ILR implant were identified, e.g. by more
      appropriate use of tests recommended in the initial evaluation, by decreasing
      repetition of tests, and by avoiding early use of specialized and expensive
      tests. A structured multidisciplinary approach would be the best model to achieve
      an optimal outcome.

PMID- 25759409
TI  - Ventricular arrhythmias with superior axis originating from the left ventricular
      septum: electrocardiographic characteristics predicting successful ablation and
      insights into their mechanism-observations from a small series of patients.
AB  - AIMS: This study aimed to evaluate the electrocardiographic characteristics and
      predictors of successful ablation for ventricular arrhythmias (VAs) with superior
      axis originating in the ventricular septum. METHODS AND RESULTS: This study
      included 385 consecutive patients with VAs undergoing radiofrequency ablation
      (RFA). Of these, 14 patients (3.7%) were identified who had VAs with superior
      axis that were mapped to and ablated at the left ventricular (LV) septum. These
      patients were classified into two groups, successful (n = 9, Success-RFA) and
      failed (n = 5, Fail-RFA) ablation. The QRS duration of the VAs was longer in the
      Success-RFA than the Fail-RFA [median (25%, 75% quartile), 140 (134, 149) vs. 128
      (116, 132) ms; P = 0.007]. In the Success-RFA, the QRS morphology in lead V1
      exhibited qR or rSR (r < 0.2 mV) pattern. In the Fail-RFA, QRS in lead V1
      demonstrated an initial R-wave of >=0.2 mV except for one patient who
      demonstrated a qR pattern. The initial R-wave amplitude of <0.2 mV in lead V1
      identified successful ablation cases with 100% sensitivity and 80% specificity.
      The magnitude of the initial R-wave amplitude in lead V1 could be related to the
      originating site's depth within the septal tissue, which could also explain the
      RFA results. CONCLUSION: Four percent of VA patients had superior axis on
      electrocardiogram and foci that mapped to the LV septum, two-thirds of which were
      successfully ablated. The initial R-wave amplitude of <0.2 mV in lead V1
      identified RFA success with high sensitivity and specificity.

PMID- 25759410
TI  - Unmasking the dormant pulmonary vein conduction with adenosine administration
      after pulmonary vein isolation with laser energy.
AB  - AIMS: The isolation of the pulmonary veins (PVs) is the mainstay of atrial
      fibrillation (AF) ablation, which with current ablation techniques can be
      achieved in almost all cases. Reconnection of PVs constitutes the most frequent
      cause of AF recurrence. Visually guided laser balloon ablation (VGLA) is a novel
      system with very high rate of persistence of pulmonary vein isolation (PVI) three
      months after the first procedure shown in preclinical and clinical studies. We
      aimed to determine the acute efficiency of the laser energy during PVI with the
      help of adenosine provocation. METHODS AND RESULTS: Twenty-six patients (19 male;
      mean age 64 +/- 9 years) with symptomatic paroxysmal AF were included in the
      study. Pulmonary vein isolation was performed using the VGLA system. After
      successful PVI, we studied the effects of intravenous adenosine (18 mg) on
      activation of each PV at least 20 min after PVI. A total of 104 PVs were
      targeted. The balloon catheter could not be placed in two PVs. Of the remaining
      102 PVs 99 (97% of the ablated PVs) could be successfully isolated. Adenosine was
      administered for each isolated PV in 25 patients. Only six PVs (6.7%) in five
      patients (20%) showed a PV reconnection during adenosine provocation. CONCLUSION:
      Pulmonary vein isolation with VGLA is a feasible technique for PVI with a very
      effective acute lesion formation. The clinical significance of this low
      reconnection rate has to be determined.

PMID- 25759411
TI  - Mesenchymal stem cell-conditioned medium improves the proliferation and migration
      of keratinocytes in a diabetes-like microenvironment.
AB  - The impairment of wound healing in diabetic patients is an important clinical
      problem. Proper keratinocyte migration and proliferation are the crucial steps
      during reepithelialization, and these steps may be impaired in diabetes mellitus
      (DM) due to hyperglycemia and chronic inflammation in wound site. In this study,
      we explored the effects of diabetes-like microenvironment with high glucose (HG)
      and intense inflammation on the migration and proliferation of keratinocytes in
      vitro. We found that the migration and proliferation of rat keratinocytes were
      reduced with HG and lipopolysaccharide (LPS) stimulation via Erk signaling
      pathway in a reactive oxygen species (ROS)-dependent manner. Nevertheless,
      mesenchymal stem cell-conditioned medium (MSC-CM) counteracts the effects of HG
      and LPS. Treatment of rat keratinocyte with MSC-CM decreased HG- and/or LPS
      induced ROS overproduction. Furthermore, MSC-CM reversed the downregulation of
      phosphorylation of MEK1/2 and Erk 1/2, which was induced by HG and/or LPS without
      affecting total levels. Our results may provide a possible mechanism for delayed
      wound healing in DM and provide a foundation to develop MSC-CM as an alternative
      therapeutic strategy to ameliorate the poor wound-healing conditions. 

PMID- 25759412
TI  - Hypoxia regulates the therapeutic potential of mesenchymal stem cells through
      enhanced autophagy.
AB  - Bone marrow-derived mesenchymal stem cells (BM-MSCs)have great therapeutic
      potential for the repair of diabetic lower-limb ischemia because of their
      proangiogenic properties. However, cells transplanted into an ischemic
      environment have reduced cell survival rates and impaired angiogenic capacity in
      vivo. We explored hypoxia pretreatment as a method to promote BM-MSC survival by
      inducing autophagy. Our results showed that hypoxic pretreatment has no effect on
      the phenotype or differentiation capacity of BM-MSCs; however, hypoxia increased
      viability and reduced apoptosis in cells treated with lipopolysaccharide.
      Immunofluorescence and western blot results showed that hypoxia pretreatment
      enhances cell autophagy mediated by elevated expression of hypoxia inducible
      factor-1alpha (HIF-1alpha). The AMPK/mTOR (adenosine monophosphate-activated
      protein kinase/mammalian target of rapamycin) signaling pathway was also
      activated in BM-MSCs during hypoxia-enhanced autophagy. It is important to note
      that hypoxia pretreatment in BM-MSCs significantly enhanced cell survival and
      promoted angiogenesis in the lower limb of ischemic diabetic rats. In conclusion,
      hypoxia pretreatment enhances survival in BM-MSCs, promoting angiogenesis by
      increasing autophagy and significantly decreasing apoptosis. Therefore,
      modulation of autophagy with hypoxic pretreatment may provide a novel strategy to
      improve MSC-based therapies. 

PMID- 25759413
TI  - Healing rate and autoimmune safety of full-thickness wounds treated with fish
      skin acellular dermal matrix versus porcine small-intestine submucosa: a
      noninferiority study.
AB  - A novel product, the fish skin acellular dermal matrix (ADM) has recently been
      introduced into the family of biological materials for the treatment of wounds.
      Hitherto, these products have been produced from the organs of livestock. A
      noninferiority test was used to compare the effect of fish skin ADM against
      porcine small-intestine submucosa extracellular matrix in the healing of 162 full
      thickness 4-mm wounds on the forearm of 81 volunteers. The fish skin product was
      noninferior at the primary end point, healing at 28 days. Furthermore, the wounds
      treated with fish skin acellular matrix healed significantly faster. These
      results might give the fish skin ADM an advantage because of its environmental
      neutrality when compared with livestock-derived products. The study results on
      these acute full-thickness wounds might apply for diabetic foot ulcers and other
      chronic full-thickness wounds, and the shorter healing time for the fish skin
      treated group could influence treatment decisions. To test the autoimmune
      reactivity of the fish skin, the participants were tested with the following
      ELISA (enzyme-linked immunosorbent assay) tests: RF, ANA, ENA, anti ds-DNA, ANCA,
      anti-CCP, and anticollagen I and II. These showed no reactivity. The results
      demonstrate the claims of safety and efficacy of fish skin ADM for wound care. 

PMID- 25759414
TI  - Changes in Bacterial Profiles and Antibiotic Sensitivity Before and After Wound
      Bed Preparation for Diabetic Foot Ulcers.
AB  - We aimed to investigate the characteristics of bacterial profiles and antibiotic
      sensitivity in diabetic foot ulcers before and after wound bed preparation. This
      study involved 423 diabetic patients with Wagner grades 1 to 4 foot ulcers.
      Secretion culture was performed before wound bed preparation. The observation
      endpoint was when the wound showed a tendency toward healing and a specialist
      determined that stopping antibiotic treatment would not affect wound healing. A
      second secretion culture was performed after the observation endpoint. We
      obtained results from both secretion cultures from 411 patients. The proportion
      of multi-drug-resistant (MDR) gram-positive bacteria was 22.0% and 47.8% before
      and after treatment, respectively; that for gram-negative bacteria was 3.5% and
      19.2%, respectively (P < .05). Pretreatment antibiotic sensitivity of
      staphylococci and other gram-positive bacteria was 48.7% and 44.8%, respectively;
      the rates decreased significantly after treatment to 36.8% (P = .031) and 34.8%
      (P = .027), respectively. Pretreatment antibiotic sensitivity of common and
      nonfermenting rare gram-negative bacteria was 55.4% and 54.6%, respectively,
      which decreased substantially after treatment to 33.2% (P = .002) and 32.9% (P =
      .003), respectively. Wound healing was achieved in 92.7% of patients.
      Pretreatment and posttreatment C-reactive protein levels were 124.759 +/- 71.58
      mg/dL and 82.8 +/- 53.61 mg/dL, respectively (P < .05). In conclusion, following
      wound bed preparation for diabetic foot ulcers, MDR bacteria numbers were
      increased and antibiotic sensitivity was decreased; inflammation was decreased.
      These findings warrant future studies for confirmation. 

PMID- 25759419
TI  - Science and culture: high concept art and experiments.

PMID- 25759418
TI  - Lidocaine 10% spray to the cervix reduces pain during intrauterine device
      insertion: a double-blind randomised controlled trial.
AB  - OBJECTIVE: Fear of pain during intrauterine device (IUD) insertion can be a
      barrier to widespread use of this safe and highly effective contraceptive method.
      Our objective was to determine the effectiveness of topical 10% lidocaine spray
      for pain control during IUD insertion. METHODS: A total of 200 subjects with the
      request for IUD insertion were included in the study. The patients were randomly
      divided into two groups: lidocaine spray (n=100) and placebo (n=100). The pain
      experienced during the procedure was measured immediately after insertion by a
      standard Visual Analogue Scale (VAS) administered by a separate researcher with
      maintenance of allocation concealment. RESULTS: The mean pain score during the
      procedure was 1.01+/-1.20 in the lidocaine spray group and 3.23+/-1.60 in the
      placebo spray group (p<0.001). Lidocaine spray treatment significantly lowered
      the overall procedural pain score compared with placebo. CONCLUSIONS: Significant
      pain reduction during IUD insertion can be achieved by using 10% lidocaine spray
      alone. Lidocaine spray can be accepted as a non-invasive, easy to apply and more
      comfortable local anaesthetic method for IUD insertion. TRIAL REGISTRATION
      NUMBER: NCT02020551.

PMID- 25759420
TI  - Inner workings: fishing for a future.

PMID- 25759421
TI  - Mastering malaria: what helps and what hurts.

PMID- 25759423
TI  - Kinetic Models for Predicting Cervical Cancer Response to Radiation Therapy on
      Individual Basis Using Tumor Regression Measured In Vivo With Volumetric Imaging.
AB  - This article describes a macroscopic mathematical modeling approach to capture
      the interplay between solid tumor evolution and cell damage during radiotherapy.
      Volume regression profiles of 15 patients with uterine cervical cancer were
      reconstructed from serial cone-beam computed tomography data sets, acquired for
      image-guided radiotherapy, and used for model parameter learning by means of a
      genetic-based optimization. Patients, diagnosed with either squamous cell
      carcinoma or adenocarcinoma, underwent different treatment modalities (image
      guided radiotherapy and image-guided chemo-radiotherapy). The mean volume at the
      beginning of radiotherapy and the end of radiotherapy was on average 23.7 cm(3)
      (range: 12.7-44.4 cm(3)) and 8.6 cm(3) (range: 3.6-17.1 cm(3)), respectively. Two
      different tumor dynamics were taken into account in the model: the viable
      (active) and the necrotic cancer cells. However, according to the results of a
      preliminary volume regression analysis, we assumed a short dead cell resolving
      time and the model was simplified to the active tumor volume. Model learning was
      performed both on the complete patient cohort (cohort-based model learning) and
      on each single patient (patient-specific model learning). The fitting results
      (mean error: ~ 16% and ~ 6% for the cohort-based model and patient-specific
      model, respectively) highlighted the model ability to quantitatively reproduce
      tumor regression. Volume prediction errors of about 18% on average were obtained
      using cohort-based model computed on all but 1 patient at a time (leave-one-out
      technique). Finally, a sensitivity analysis was performed and the data
      uncertainty effects evaluated by simulating an average volume perturbation of
      about 1.5 cm(3) obtaining an error increase within 0.2%. In conclusion, we showed
      that simple time-continuous models can represent tumor regression curves both on
      a patient cohort and patient-specific basis; this discloses the opportunity in
      the future to exploit such models to predict how changes in the treatment
      schedule (number of fractions, doses, intervals among fractions) might affect the
      tumor regression on an individual basis.

PMID- 25759424
TI  - Tumor Hypoxia Response After Targeted Therapy in EGFR-Mutant Non-Small Cell Lung
      Cancer: Proof of Concept for FMISO-PET.
AB  - Hypoxia is associated with resistance to radiotherapy and chemotherapy.
      Functional imaging of hypoxia in non-small cell lung cancer (NSCLC) could allow
      early assessment of tumor response and guide subsequent therapies. Epidermal
      growth factor receptor (EGFR) inhibition with erlotinib reduces hypoxia in vivo.
      [18F]-Fluoromisonidazole (FMISO) is a radiolabeled tracer that selectively
      accumulates in hypoxic cells. We sought to determine whether FMISO positron
      emission tomography (FMISO-PET) could detect changes in hypoxia in vivo in
      response to EGFR-targeted therapy. In a preclinical investigation, nude mice with
      human EGFR-mutant lung adenocarcinoma xenografts underwent FMISO-PET scans before
      and 5 days after erlotinib or empty vehicle initiation. Descriptive statistics
      and analysis of variance (ANOVA) tests were used to analyze changes in
      standardized uptake value (SUV), with pooled analyses for the mice in each group
      (baseline, postvehicle, and posterlotinib). In a small correlative pilot human
      study, patients with EGFR-mutant metastatic NSCLC underwent FMISO-PET scans
      before and 10 to 12 days after erlotinib initiation. Changes in SUV were compared
      to standard chest computed tomography (CT) scans performed 6 weeks after
      erlotinib initiation. The mean (+/-standard error of the mean; SUVmean) of the
      xenografts was 0.17 +/- 0.014, 0.14 +/- 0.008, and 0.06 +/- 0.004 for baseline,
      postvehicle, and posterlotinib groups, respectively, with lower SUVmean among the
      posterlotinib group compared to other groups (P < .05). Changes on preclinical
      PET imaging were striking, with near-complete disappearance of FMISO uptake after
      erlotinib initiation. Two patients were enrolled on the pilot study. In the first
      patient, SUVmean increased by 21% after erlotinib, with progression on 6-week
      chest CT followed by death after 4.8 months. In the second patient, SUVmean
      decreased by 7% after erlotinib, with regression on 6-week chest CT accompanied
      by clinical improvement; the patient had stable disease at 14.5 months. In
      conclusion, we observed that FMISO-PET can detect changes in hypoxia levels after
      EGFR-directed therapy in EGFR-mutant NSCLC. Further study is warranted to
      determine its utility as an imaging biomarker of early response to EGFR-directed
      therapy. 

PMID- 25759425
TI  - The Pocketable Electronic Devices in Radiation Oncology (PEDRO) Project: How the
      Use of Tools in Medical Decision Making is Changing?
AB  - PURPOSE: To analyze the impact of mobile electronic devices (MEDs) and apps in
      the daily clinical activity of young radiation or clinical oncologists in 5
      Western European countries (Italy, Germany, Spain, Portugal, and Denmark).
      METHODS: A web-based questionnaire was sent to 462 young (<=40 years) members of
      the national radiation or clinical oncology associations of the countries
      involved in the study. The 15 items investigated diffusion of MEDs (smartphones
      and/or tablets), their impact on daily clinical activity, and the differences
      perceived by participants along time. RESULTS: A total of 386 (83.5%) of the 462
      correctly filled questionnaires were statistically evaluated. Up to 65% of
      respondents declared to use an electronic device during their clinical activity.
      Conversely, 72% considered low to moderate impact of smartphones/tables on their
      daily practice. The daily use significantly increased from 2009 to 2012: users
      reporting a use >=6 times/d raised from 5% to 39.9%. Professional needs
      fulfillment was declared by less than 68% of respondents and compliance to apps
      indications by 66%. Significant differences were seen among the countries, in
      particular concerning the feeling of usefulness of MEDs in the daily clinical
      life. The perception of the need of a comprehensive Web site containing a variety
      of applications (apps) for clinical use significantly differed among countries in
      2009, while it was comparable in 2012. CONCLUSIONS: This survey showed a large
      diffusion of MEDs in young professionals working in radiation oncology. Looking
      at these data, it is important to verify the consistency of information found
      within apps, in order to avoid potential errors eventually detrimental for
      patients. "Quality assurance" criteria should be specifically developed for
      medical apps and a comprehensive Web site gathering all reliable applications and
      tools might be useful for daily clinical practice.

PMID- 25759426
TI  - Preparation and In Vitro Evaluation of Antitumor Activity of TGFalphaL3-SEB as a
      Ligand-Targeted Superantigen.
AB  - Tumor-targeted superantigens (TTSs) have been used to treat a variety of tumors
      in preclinical studies. The TTS utilizes the powerful T-cell activation strategy
      by means of staphylococcal enterotoxins (SEs) as superantigens (Sags) to target
      tumor cells. Monoclonal antibodies and tumor-related ligands have been used as
      targeting molecules of Sag. In this study, we assessed the antitumor potency of
      tumor-targeted superantigen (TTS) strategy to design and produce fusion protein
      as a new antitumor candidate. The third loop (L3) of transforming growth factor
      alpha (TGF-alpha) was genetically conjugated to staphylococcal enterotoxin type B
      (TGFalphaL3-SEB), and its in vitro antitumor activity against murine breast
      cancer cells (A431 cell line) was evaluated. We designed and prepared TGFalphaL3
      SEB chimeric protein and evaluated superantigenic activity, binding property to
      cancer cells, overexpression of epidermal growth factor receptor (EGFR), and in
      vitro antitumor activities. Cloning of tgfalphal3-seb was confirmed by colony
      polymerase chain reaction, enzymatic digestion, and sequencing. The recombinant
      TGFalphaL3-SEB fusion protein with molecular weight of 31 kDa was expressed and
      confirmed by anti-His Western-blot analysis. The TGFalphaL3-SEB fusion protein
      attached to A431 cell line with proper affinity and induced dose-dependent
      cytotoxicity against EGFR-expressing cancer cells in vitro. The TGFalphaL3-SEB
      chimeric protein exhibited potent in vitro antitumor activity. Our findings
      indicated that TGFalphaL3-SEB may be a promising anticancer candidate in cancer
      immunotherapy, and further studies are required to explore its potential in vivo
      therapeutic applications. 

PMID- 25759427
TI  - Targeting Accuracy of Image-Guided Radiosurgery for Intracranial Lesions: A
      Comparison Across Multiple Linear Accelerator Platforms.
AB  - PURPOSE: To evaluate the overall positioning accuracy of image-guided
      intracranial radiosurgery across multiple linear accelerator platforms. METHODS:
      A computed tomography scan with a slice thickness of 1.0 mm was acquired of an
      anthropomorphic head phantom in a BrainLAB U-frame mask. The phantom was embedded
      with three 5-mm diameter tungsten ball bearings, simulating a central, a left,
      and an anterior cranial lesion. The ball bearings were positioned to radiation
      isocenter under ExacTrac X-ray or cone-beam computed tomography image guidance on
      3 Linacs: (1) ExacTrac X-ray localization on a Novalis Tx; (2) cone-beam computed
      tomography localization on the Novalis Tx; (3) cone-beam computed tomography
      localization on a TrueBeam; and (4) cone-beam computed tomography localization on
      an Edge. Each ball bearing was positioned 5 times to the radiation isocenter with
      different initial setup error following the 4 image guidance procedures on the 3
      Linacs, and the mean (u) and one standard deviation (sigma) of the residual error
      were compared. RESULTS: Averaged overall 3 ball bearing locations, the vector
      length of the residual setup error in mm (u +/- sigma) was 0.6 +/- 0.2, 1.0 +/-
      0.5, 0.2 +/- 0.1, and 0.3 +/- 0.1 on ExacTrac X-ray localization on a Novalis Tx,
      cone-beam computed tomography localization on the Novalis Tx, cone-beam computed
      tomography localization on a TrueBeam, and cone-beam computed tomography
      localization on an Edge, with their range in mm being 0.4 to 1.1, 0.4 to 1.9, 0.1
      to 0.5, and 0.2 to 0.6, respectively. The congruence between imaging and
      radiation isocenters in mm was 0.6 +/- 0.1, 0.7 +/- 0.1, 0.3 +/- 0.1, and 0.2 +/-
      0.1, for the 4 systems, respectively. CONCLUSIONS: Targeting accuracy comparable
      to frame-based stereotactic radiosurgery can be achieved with image-guided
      intracranial stereotactic radiosurgery treatment.

PMID- 25759428
TI  - Community Protection Policies and Repeat Sexual Offenses in Florida.
AB  - The purpose of this study was to investigate the impact of sexual offender
      management policies on sex crime repeat arrest rates in Florida. Aggregate data
      for the period 1990 to 2010 were provided by the Florida Department of Law
      Enforcement. The repeat offense rate was defined as the proportion of arrests
      each year that were committed by individuals with a previous conviction in the
      same crime category. The average yearly repeat offense rate for sex crimes was
      6.5%, which was consistently and significantly lower than rates for other crimes:
      8.3% for non-sex assaults, 15.1% for robbery, 29.8% for drug offenses, and 11.6%
      for DUI. The average annual sexual repeat arrest rate prior to and after the
      implementation of sexual offender registration laws in 1997 was 4.9% and 7.5%,
      respectively, indicating a statistically significant increase. The average annual
      repeat arrest rates for non-sex assaults, robberies, drug crimes, and DUIs also
      increased after 1997. No significant differences were found when comparing the
      average annual percent change for sexual re-arrest (+3.47%) with non-sexual
      assault (+3.93%), robbery (-.73%), drug offenses (+1.59%), and DUI (+1.14). Sex
      crime repeat arrests in Florida do not appear to show a decline attributable to
      sex offender management policies implemented since 1997. 

PMID- 25759429
TI  - Jail Mental Health Resourcing: A Conceptual and Empirical Study of Social
      Determinants.
AB  - U.S. county jails hold large populations of mentally ill inmates but have rarely
      been researched quantitatively to assess their collective capacity for providing
      mental health treatment. This research uses ordinal logit and a partial parallel
      slopes model and a large sample of U.S. counties to assess conceptualized links
      between local institutional and structural indicators and jail mental health
      resourcing. Strong church networks and high rates of adult education completion
      are associated with enhanced jail mental health resourcing. Urbanized areas and
      areas with deep economic ties to manufacturing appear supportive of a strong jail
      mental health system. Conversely, conservative political environments and areas
      with strong medical and mental health networks based in the community are
      correlated with reduced jail mental health resourcing. Evidence from this
      research adds to a growing understanding of the need for enhanced community
      mental health service and diagnostic capabilities in our nation's jails, noting
      the characteristics and correlates of model program jurisdictions and
      jurisdictions where program enhancements are most likely in order. 

PMID- 25759430
TI  - Predicting Bullying: Exploring the Contributions of Childhood Negative Life
      Experiences in Predicting Adolescent Bullying Behavior.
AB  - Although there has been much interest in research on aggression and in particular
      bullying, a relatively less charted area of research has centered on articulating
      a better understanding of the mechanisms and processes by which persons are at
      increased risk for bullying. Furthermore, those studies that have investigated
      the linkages between childhood experiences and bullying perpetration have been
      limited with respect to definitional and operational issues, reliance on cross
      sectional data, and the lack of assessing competing explanations of bullying
      perpetration. Using five waves of data from a community-based longitudinal sample
      of children followed through age 18 (N = 763), the current study examines the
      extent to which childhood negative life events in a variety of domains predict
      adolescent bullying. Results show that early childhood experiences, particularly
      those within the family and school domains, may alter life trajectories and can
      act as predictors for later adolescent bullying, thereby underscoring the
      potential importance that relatively minor experiences can have over the long
      term. Implications for future research based on these analyses are examined. 

PMID- 25759431
TI  - Process Evaluation of Practice-based Diabetes Prevention Programs: What Are the
      Implementation Challenges?
AB  - PURPOSE: The purpose of this report is to describe lessons learned about the
      feasibility of recruitment and implementation of low-income adults with
      prediabetes in primary care clinics into diabetes prevention programs. METHODS:
      Mixed methods process evaluation of a pragmatic 2-group pilot comparative
      effectiveness study of a community-developed Healthy Living Program (HLP) and a
      Diabetes Prevention Program (DPP) with 58 adults. RESULTS: Of the total (n =
      1215) assessed for eligibility, 7% (n = 92) were randomized, 58 completed the
      baseline assessment, and 31 completed the intervention. The process evaluation
      identified difficulty in systematically screening potentially eligible patients.
      There were several logistic and staffing challenges with program planning and
      initial start-up. CONCLUSIONS: Addressing challenges to feasibility is required
      for successful translation of evidence-based programs to clinical settings.

PMID- 25759432
TI  - In vivo horizontal gene transfer of the carbapenemase OXA-48 during a nosocomial
      outbreak.
AB  - BACKGROUND: OXA-48 is a highly prevalent carbapenemase and has been isolated
      worldwide. Here, we investigate the in vivo horizontal gene transfer (HGT) of
      blaOXA-48 from Klebsiella pneumoniae to Escherichia coli in an infected patient.
      METHODS: Bacterial isolates were characterized by susceptibility testing,
      multilocus sequence typing, DiversiLab, and plasmid analyses. Transferability of
      blaOXA-48 was evaluated by in vitro transconjugation using the outbreak strain
      and E. coli J53. In vivo transconjugation was investigated using the larvae of
      the greater wax moth (Galleria mellonella) and low-complexity-microbiota mice.
      RESULTS: OXA-48-harboring K. pneumoniae isolates belonging to ST14 were isolated
      during a nosocomial outbreak from 6 patients. Molecular and epidemiological
      analyses revealed the HGT of an approximately 60-kb OXA-48-containing IncL/M-type
      plasmid from K. pneumoniae to E. coli belonging to the novel ST666 in a patient.
      In vitro conjugation experiments revealed a transconjugation frequency of 8.7 *
      10(-7). HGT of OXA-48 in a newly developed in vivo model using G. mellonella
      larvae revealed a higher transconjugation frequency of 1.3 * 10(-4). The
      conjugation frequency of OXA-48 from K. pneumoniae and E. coli in the gut of low
      complexity-microbiota mice was determined to be 2.9 * 10(-5). CONCLUSIONS: The in
      vivo intergenus gene transfer of OXA-48 in the gut of an infected patient was
      verified in vitro and in 2 in vivo models, which both showed even higher
      transmission frequencies vs in vitro conditions. This implies that the current in
      vitro protocols might not correctly reflect the HGT of carbapenemase genes in
      vivo.

PMID- 25759433
TI  - Increased statin prescribing does not lower pneumonia risk.
AB  - BACKGROUND: Investigators have attributed protective effects of statins against
      pneumonia and other infections. However, these reports are based on observational
      data where treatments are not assigned randomly. We aimed to determine if the
      protective effects of statins against pneumonia are due to nonrandom treatment
      assignment. METHODS: We built a cohort consisting of 124 695 Medicare
      beneficiaries diagnosed with an acute myocardial infarction (AMI) for which we
      had complete claims data. We considered patients who survived at least 30 days
      post-AMI (full sample), or who survived for 1 year post-AMI (survivors). First,
      we used ordinary least squares (OLS) and logit models to determine if receiving a
      statin was protective against pneumonia. Second, to control for nonrandom
      treatment assignment, we performed an instrumental variables analysis using
      geographic treatment rates as an instrument. All models included patient
      demographics, medications, diagnoses, length of hospital stay, and out-of-pocket
      drug costs as covariates. Our outcome measure was a pneumonia diagnosis during
      the 1 year following AMI. RESULTS: A total of 76 994 patients (61.9%) filled a
      statin prescription, and 19 078 (15.3%) were diagnosed with pneumonia. Using OLS,
      the statin coefficient was -0.016 (P < .001), indicating that statins are
      associated with a reduction in pneumonia. Using instrumental variables, we find
      that statin prescriptions are not associated with a reduction in pneumonia. For
      the full sample, statin coefficients ranged from -0.001 to -0.01 (P > .6).
      CONCLUSIONS: For patients with AMI, the protective effect of statins against
      pneumonia is most likely the result of nonrandom treatment assignment (ie, a
      healthy-user bias).

PMID- 25759434
TI  - Proteomic Analysis of Human Pluripotent Stem Cell-Derived, Fetal, and Adult
      Ventricular Cardiomyocytes Reveals Pathways Crucial for Cardiac Metabolism and
      Maturation.
AB  - BACKGROUND: Differentiation of pluripotent human embryonic stem cells (hESCs) to
      the cardiac lineage represents a potentially unlimited source of ventricular
      cardiomyocytes (VCMs), but hESC-VCMs are developmentally immature. Previous
      attempts to profile hESC-VCMs primarily relied on transcriptomic approaches, but
      the global proteome has not been examined. Furthermore, most hESC-CM studies
      focus on pathways important for cardiac differentiation, rather than regulatory
      mechanisms for CM maturation. We hypothesized that gene products and pathways
      crucial for maturation can be identified by comparing the proteomes of hESCs,
      hESC-derived VCMs, human fetal and human adult ventricular and atrial CMs.
      METHODS AND RESULTS: Using two-dimensional-differential-in-gel electrophoresis,
      121 differentially expressed (>1.5-fold; P<0.05) proteins were detected. The data
      set implicated a role of the peroxisome proliferator-activated receptor alpha
      signaling in cardiac maturation. Consistently, WY-14643, a peroxisome
      proliferator-activated receptor alpha agonist, increased fatty oxidative enzyme
      level, hyperpolarized mitochondrial membrane potential and induced a more
      organized morphology. Along this line, treatment with the thyroid hormone
      triiodothyronine increased the dynamic tension developed in engineered human
      ventricular cardiac microtissue by 3-fold, signifying their maturation.
      CONCLUSIONS: We conclude that the peroxisome proliferator-activated receptor
      alpha and thyroid hormone pathways modulate the metabolism and maturation of hESC
      VCMs and their engineered tissue constructs. These results may lead to mechanism
      based methods for deriving mature chamber-specific CMs.

PMID- 25759436
TI  - Reply to Margalida and Colomer: Science should strive to prevent mistakes, not
      corrections.

PMID- 25759435
TI  - Aortic Disease Presentation and Outcome Associated With ACTA2 Mutations.
AB  - BACKGROUND: ACTA2 mutations are the major cause of familial thoracic aortic
      aneurysms and dissections. We sought to characterize these aortic diseases in a
      large case series of individuals with ACTA2 mutations. METHODS AND RESULTS:
      Aortic disease, management, and outcome associated with the first aortic event
      (aortic dissection or aneurysm repair) were abstracted from the medical records
      of 277 individuals with 41 various ACTA2 mutations. Aortic events occurred in 48%
      of these individuals, with the vast majority presenting with thoracic aortic
      dissections (88%) associated with 25% mortality. Type A dissections were more
      common than type B dissections (54% versus 21%), but the median age of onset of
      type B dissections was significantly younger than type A dissections (27 years
      versus 36 years). Only 12% of aortic events were repair of ascending aortic
      aneurysms, which variably involved the aortic root, ascending aorta, and aortic
      arch. Overall, cumulative risk of an aortic event at age 85 years was 0.76 (95%
      confidence interval, 0.64-0.86). After adjustment for intrafamilial correlation,
      sex and race, mutations disrupting p.R179 and p.R258 were associated with
      significantly increased risk for aortic events, whereas p.R185Q and p.R118Q
      mutations showed significantly lower risk of aortic events compared with other
      mutations. CONCLUSIONS: ACTA2 mutations are associated with high risk of
      presentation with an acute aortic dissection. The lifetime risk for an aortic
      event is only 76%, suggesting that additional environmental or genetic factors
      play a role in expression of aortic disease in individuals with ACTA2 mutations.

PMID- 25759437
TI  - Heme-thiolate ferryl of aromatic peroxygenase is basic and reactive.
AB  - A kinetic and spectroscopic characterization of the ferryl intermediate (APO-II)
      from APO, the heme-thiolate peroxygenase from Agrocybe aegerita, is described.
      APO-II was generated by reaction of the ferric enzyme with
      metachloroperoxybenzoic acid in the presence of nitroxyl radicals and detected
      with the use of rapid-mixing stopped-flow UV-visible (UV-vis) spectroscopy. The
      nitroxyl radicals served as selective reductants of APO-I, reacting only slowly
      with APO-II. APO-II displayed a split Soret UV-vis spectrum (370 nm and 428 nm)
      characteristic of thiolate ligation. Rapid-mixing, pH-jump spectrophotometry
      revealed a basic pKa of 10.0 for the Fe(IV)-O-H of APO-II, indicating that APO-II
      is protonated under typical turnover conditions. Kinetic characterization showed
      that APO-II is unusually reactive toward a panel of benzylic C-H and phenolic
      substrates, with second-order rate constants for C-H and O-H bond scission in the
      range of 10-10(7) M(-1)?s(-1). Our results demonstrate the important role of the
      axial cysteine ligand in increasing the proton affinity of the ferryl oxygen of
      APO intermediates, thus providing additional driving force for C-H and O-H bond
      scission. 

PMID- 25759438
TI  - Motor role of parietal cortex in a monkey model of hemispatial neglect.
AB  - Parietal cortex is central to spatial cognition. Lesions of parietal cortex often
      lead to hemispatial neglect, an impairment of choices of targets in space. It has
      been unclear whether parietal cortex implements target choice at the general
      cognitive level, or whether parietal cortex subserves the choice of targets of
      particular actions. To address this question, monkeys engaged in choice tasks in
      two distinct action contexts--eye movements and arm movements. We placed focused
      reversible lesions into specific parietal circuits using the GABAA receptor
      agonist muscimol and validated the lesion placement using MRI. We found that
      lesions on the lateral bank of the intraparietal sulcus [lateral intraparietal
      area (LIP)] specifically biased choices made using eye movements, whereas lesions
      on the medial bank of the intraparietal sulcus [parietal reach region (PRR)]
      specifically biased choices made using arm movements. This double dissociation
      suggests that target choice is implemented in dedicated parietal circuits in the
      context of specific actions. This finding emphasizes a motor role of parietal
      cortex in spatial choice making and contributes to our understanding of
      hemispatial neglect.

PMID- 25759439
TI  - Triassic-Jurassic climate in continental high-latitude Asia was dominated by
      obliquity-paced variations (Junggar Basin, Urumqi, China).
AB  - Empirical constraints on orbital gravitational solutions for the Solar System can
      be derived from the Earth's geological record of past climates. Lithologically
      based paleoclimate data from the thick, coal-bearing, fluvial-lacustrine
      sequences of the Junggar Basin of Northwestern China (paleolatitude ~60 degrees )
      show that climate variability of the warm and glacier-free high latitudes of the
      latest Triassic-Early Jurassic (~198-202 Ma) Pangea was strongly paced by
      obliquity-dominated (~40 ky) orbital cyclicity, based on an age model using the
      405-ky cycle of eccentricity. In contrast, coeval low-latitude continental
      climate was much more strongly paced by climatic precession, with virtually no
      hint of obliquity. Although this previously unknown obliquity dominance at high
      latitude is not necessarily unexpected in a high CO2 world, these data deviate
      substantially from published orbital solutions in period and amplitude for
      eccentricity cycles greater than 405 ky, consistent with chaotic diffusion of the
      Solar System. In contrast, there are indications that the Earth-Mars orbital
      resonance was in today's 2-to-1 ratio of eccentricity to inclination. These
      empirical data underscore the need for temporally comprehensive, highly reliable
      data, as well as new gravitational solutions fitting those data. 

PMID- 25759440
TI  - Breakdown of the brain's functional network modularity with awareness.
AB  - Neurobiological theories of awareness propose divergent accounts of the spatial
      extent of brain changes that support conscious perception. Whereas focal theories
      posit mostly local regional changes, global theories propose that awareness
      emerges from the propagation of neural signals across a broad extent of sensory
      and association cortex. Here we tested the scalar extent of brain changes
      associated with awareness using graph theoretical analysis applied to functional
      connectivity data acquired at ultra-high field while subjects performed a simple
      masked target detection task. We found that awareness of a visual target is
      associated with a degradation of the modularity of the brain's functional
      networks brought about by an increase in intermodular functional connectivity.
      These results provide compelling evidence that awareness is associated with truly
      global changes in the brain's functional connectivity. 

PMID- 25759441
TI  - Mistake index as a surrogate of quality in scientific manuscripts.

PMID- 25759442
TI  - Decision-making for destination therapy left ventricular assist devices:
      implications for caregivers.
AB  - BACKGROUND: Implanting centers often require the identification of a dedicated
      caregiver before destination therapy left ventricular assist device (DT LVAD)
      implantation; however, the caregiver experience surrounding this difficult
      decision is relatively unexplored. METHODS AND RESULTS: From October 2012 through
      July 2013, we conducted semistructured, in-depth interviews with caregivers of
      patients considering DT LVAD. Data were analyzed using a mixed inductive and
      deductive approach. We interviewed 17 caregivers: 10 caregivers of patients
      living with DT LVAD, 6 caregivers of patients who had died with DT LVAD, and 1
      caregiver of a patient who had declined DT LVAD. The themes identified, which
      could also be considered dialectical tensions, are broadly interpreted under 3
      domains mapping to decision context, process, and outcome: (1) the stark decision
      context, with tension between hope and reality; (2) the challenging decision
      process, with tension between wanting loved ones to live and wanting to respect
      loved ones' wishes; and (3) the downstream decision outcome, with tension between
      gratitude and burden. CONCLUSIONS: Decision-making surrounding DT LVAD should
      incorporate decision support for patients and caregivers. This should include a
      focus on caregiver burden and the predictable tensions that caregivers
      experience.

PMID- 25759444
TI  - Family caregiving: benefits and burdens.

PMID- 25759443
TI  - Perfect storm: concurrent stress and depressive symptoms increase risk of
      myocardial infarction or death.
AB  - BACKGROUND: Depression and stress have each been found to be associated with poor
      prognosis in patients with coronary heart disease. A recently offered
      psychosocial perfect storm conceptual model hypothesizes amplified risk will
      occur in those with concurrent stress and depressive symptoms. We tested this
      hypothesis in a large sample of US adults with coronary heart disease. METHODS
      AND RESULTS: Participants included 4487 adults with coronary heart disease from
      the REasons for Geographic and Racial Differences in Stroke study, a prospective
      cohort study of 30,239 black and white adults. We conducted Cox proportional
      hazards regression with the composite outcome of myocardial infarction or death
      and adjustment for demographic, clinical, and behavioral factors. Overall, 6.1%
      reported concurrent high stress and high depressive symptoms at baseline. During
      a median 5.95 years of follow-up, 1337 events occurred. In the first 2.5 years of
      follow-up, participants with concurrent high stress and high depressive symptoms
      had increased risk for myocardial infarction or death (adjusted hazard ratio,
      1.48 [95% confidence interval, 1.08-2.02]) relative to those with low stress and
      low depressive symptoms. Those with low stress and high depressive symptoms
      (hazard ratio, 0.92 [95% confidence interval, 0.66-1.28]) or high stress and low
      depressive symptoms (hazard ratio, 0.86 [95% confidence interval, 0.57-1.29])
      were not at increased risk. The association on myocardial infarction or death was
      not significant after the initial 2.5 years of follow-up (hazard ratio, 0.89 [95%
      confidence interval, 0.65-1.22]). CONCLUSIONS: Our results provide initial
      support for a psychosocial perfect storm conceptual model; the confluence of
      depressive symptoms and stress on medical prognosis in adults with coronary heart
      disease may be particularly destructive in the shorter term.

PMID- 25759449
TI  - The role of the private sector in health systems.

PMID- 25759450
TI  - A total market approach for condoms in Myanmar: the need for the private, public
      and socially marketed sectors to work together for a sustainable condom market
      for HIV prevention.
AB  - BACKGROUND: Concerns about appropriate pricing strategies and the high market
      share of subsidized condoms prompted Population Services International
      (PSI)/Myanmar to adopt a total market approach (TMA). This article presents data
      on the size and composition of the Myanmar condom market, identifies
      inefficiencies and recommends methods for better targeting public subsidy.
      METHODOLOGY: Data on condom need and condom use came from PSI/Myanmar's (PSI/M's)
      behavioural surveys; data for key populations' socioeconomic status profiles came
      from the same surveys and the National Tuberculosis Prevalence Survey. Data on
      market share, volumes, value and number of condoms were from PSI/M's quarterly
      retail audits and Joint United Nations Programme on HIV/AIDS (UNAIDS). RESULTS:
      Between 2008 and 2010, the universal need for condoms decreased from 112.9 to
      98.2 million while condom use increased from 32 to 46%. Free and socially
      marketed condoms dominated the market (94%) in 2009-11 with an increase in the
      proportion of free condoms over time. The retail price of socially marketed
      condoms was artificially low at 44 kyats ($0.05 USD) in 2011 while the price for
      commercial condoms was 119-399 kyats ($0.15-$0.49 USD). Equity analyses
      demonstrated an equal distribution of female sex workers across national wealth
      quintiles, but 54% of men who have sex with men and 55% of male clients were in
      the highest two quintiles. Donor subsidies for condoms increased over time; from
      $434,000 USD in 2009 to $577,000 USD in 2011. CONCLUSION: The market for male
      condoms was stagnant in Myanmar due to: limited demand for condoms among key
      populations, the dominance of free and socially marketed condoms on the market
      and a neglected commercial sector. Subsidies for socially marketed and free
      condoms have prevented the growth of the private sector, an unintended
      consequence. A TMA is needed to grow and sustain the condom market in Myanmar,
      which requires close co-ordination between the public, socially marketed and
      commercial sectors.

PMID- 25759451
TI  - An impact evaluation of medical insurance for poor in Georgia: preliminary
      results and policy implications.
AB  - OBJECTIVE: The objective of this article is to assess the impact of the new
      health financing reform in Georgia-'medical insurance for the poor (MIP)'-which
      uses private insurance companies and delivers state-subsidized health benefits to
      the poorest groups of the Georgian population. METHODS: To evaluate the reform we
      looked at access to health care services and financial protection against health
      care costs, which are two key dimensions proposed for the universal coverage
      plans. The data from two nationally representative Health Utilization and
      Expenditure Surveys (2007 and 2010) were used, and a difference-in-difference
      method of evaluation was applied. FINDINGS: The MIP was not found to have a
      significant impact on service utilization growth nationwide, but in the capital
      city the MIP insured were 12% more likely to use formal health services and 7.6%
      more likely to use hospitals as compared with other areas of the country. The MIP
      impact on out-of-pocket health expenditures was greater in reducing costs of
      accessing services. The cost reductions were sizable and more pronounced among
      the poorest. Finally, the MIP significantly increased the odds of obtaining free
      benefits by insured individuals as compared with the control group. Such an
      increase was most noticeable for the poorest third of the population.
      CONCLUSIONS: Marginal changes in access to services and the geographically
      diverse impact of the MIP on service utilization points to other factors
      affecting health-seeking behaviour of the insured. These other factors include
      private insurer behaviour that may have used strategies for reducing claims and
      managing utilization. Equity impact of the MIP and improved financial protection,
      especially for the poor, are benefits to be retained by government policies when
      universal health coverage is rolled out nationwide and all citizens will be
      covered. The role of private insurance companies as financial intermediaries of
      the publicly funded programme needs further evaluation before moving forward.

PMID- 25759452
TI  - Private sector participation in delivering tertiary health care: a dichotomy of
      access and affordability across two Indian states.
AB  - Poor quality care in public sector hospitals coupled with the costs of care in
      the private sector have trapped India's poor in a vicious cycle of poverty, ill
      health and debt for many decades. To address this, the governments of Andhra
      Pradesh (AP) and Maharashtra (MH), India, have attempted to improve people's
      access to hospital care by partnering with the private sector. A number of
      government-sponsored schemes with differing specifications have been launched to
      facilitate this strategy. AIMS: This article aims to compare changes in access
      to, and affordability and efficiency of private and public hospital inpatient
      (IP) treatments between MH and AP from 2004 to 2012 and to assess whether the
      health financing innovations in one state resulted in larger or smaller benefits
      compared with the other. METHODS: We used data from household surveys conducted
      in 2004 and 2012 in the two states and undertook a difference-in-difference (DID)
      analysis. The results focus on hospitalization, out-of-pocket expenditure and
      length of stay. RESULTS: The average IP expenditure for private hospital care has
      increased in both states, but more so in MH. There was also an observable
      increase in both utilization of and expenditure on nephrology treatment in
      private hospitals in AP. The duration of stay recorded in days for private
      hospitals has increased slightly in MH and declined in AP with a significant DID.
      The utilization of public hospitals has reduced in AP and increased in MH.
      CONCLUSION: The state of AP appears to have benefited more than MH in terms of
      improved access to care by involving the private sector. The Aarogyasri scheme is
      likely to have contributed to these impacts in AP at least in part. Our study
      needs to be followed up with repeated evaluations to ascertain the long-term
      impacts of involving the private sector in providing hospital care.

PMID- 25759453
TI  - Who serves the urban poor? A geospatial and descriptive analysis of health
      services in slum settlements in Dhaka, Bangladesh.
AB  - In Bangladesh, the health risks of unplanned urbanization are disproportionately
      shouldered by the urban poor. At the same time, affordable formal primary care
      services are scarce, and what exists is almost exclusively provided by non
      government organizations (NGOs) working on a project basis. So where do the poor
      go for health care? A health facility mapping of six urban slum settlements in
      Dhaka was undertaken to explore the configuration of healthcare services
      proximate to where the poor reside. Three methods were employed: (1) Social
      mapping and listing of all Health Service Delivery Points (HSDPs); (2) Creation
      of a geospatial map including Global Positioning System (GPS) co-ordinates of all
      HSPDs in the six study areas and (3) Implementation of a facility survey of all
      HSDPs within six study areas. Descriptive statistics are used to examine the
      number, type and concentration of service provider types, as well as indicators
      of their accessibility in terms of location and hours of service. A total of 1041
      HSDPs were mapped, of which 80% are privately operated and the rest by NGOs and
      the public sector. Phamacies and non-formal or traditional doctors make up 75% of
      the private sector while consultation chambers account for 20%. Most NGO and
      Urban Primary Health Care Project (UPHCP) static clinics are open 5-6 days/week,
      but close by 4-5 pm in the afternoon. Evening services are almost exclusively
      offered by private HSDPs; however, only 37% of private sector health staff
      possess some kind of formal medical qualification. This spatial analysis of
      health service supply in poor urban settlements emphasizes the importance of
      taking the informal private sector into account in efforts to increase effective
      coverage of quality services. Features of informal private sector service
      provision that have facilitated market penetration may be relevant in designing
      formal services that better meet the needs of the urban poor. 

PMID- 25759454
TI  - Quality of inpatient care in public and private hospitals in Sri Lanka.
AB  - OBJECTIVE: To compare the quality of inpatient clinical care in public and
      private hospitals in Sri Lanka. METHODS: A retrospective, cross-sectional
      comparison was done of inpatient quality, in a sample of 11 public and 10 private
      hospitals in three of 25 districts. Data were collected for 55 quality indicators
      from medical records of 2523 public and 1815 private inpatient admissions. These
      covered treatment of asthma, acute myocardial infarction (AMI), childbirth and
      five other conditions, along with outcome indicators, and medicine prescribing
      indicators. RESULTS: Overall quality scores were better in the public sector than
      the private sector (77 vs 69%). Performance was similar for management of AMI and
      childbirth and somewhat better in the private sector for management of asthma.
      The public sector performed better in those indicators that are not constrained
      by resources (94 vs 81%), but worse in indicators that are highly resource
      intensive (10 vs 31%). Quality was comparable in assessment and investigation,
      but the public sector performed better in treatment and management (70 vs 62%)
      and drug prescribing (68 vs 60%), and modestly worse in terms of outcomes (92 vs
      97%). CONCLUSIONS: For a range of indicators where comparisons were possible,
      quality of inpatient clinical care in Sri Lanka was comparable to levels reported
      from upper-middle income Asian countries, and often approaches that in developed
      countries, although the findings cannot be generalized. Quality in the public
      sector is better than in the private sector in many areas, despite spending being
      substantially less. Quality in public hospitals is resource constrained, and
      needs greater government investment for improvement, but when resource
      limitations are not critical, the public sector appears able to deliver equal or
      better quality than the private sector. Overall similarities in quality between
      the two sectors suggest the importance of physician training and other factors.

PMID- 25759455
TI  - Mortality outcomes in hospitals with public, private not-for-profit and private
      for-profit ownership in Chile 2001-2010.
AB  - Public, private not-for-profit (PNFP) and private for-profit (PFP) hospitals may
      have different behaviour and performance in different indicators such as health
      outcomes, cost-efficiency and quality. Chile has a mixed healthcare system both
      in financing and service delivery. The public National Health Fund (Fondo
      Nacional de Salud) covers 76% of the population-poorer and with higher health
      risks-whereas private health insurers cover 16% of the population-richer and with
      lower health risks. The aim of the study was to analyse the in-patient mortality
      outcomes by hospital ownership in Chile. METHODS: We use hospital discharge data
      in Chile for the period 2001-10 with a total of 16,205,314 discharges in 20
      public, 6 PNFP and 15 PFP hospitals. We analyse in-patient mortality considering
      all diagnoses and a subsample considering only myocardial infarction and stroke
      diagnoses. Using a probit regression, we estimate how hospital ownership explains
      in-patient mortality controlling for other confounding variables like health and
      socioeconomic status, and hospital characteristics. RESULTS: The discharge
      condition was reported as death in 3.5% of the public hospitals' discharges, 1.3%
      in PNFP and 0.7% in PFP. PNFP and PFP hospitals show a lower risk of in-hospital
      mortality for all diagnoses, myocardial infarction and stroke in comparison with
      public hospitals. DISCUSSION: The question about which type of hospital ownership
      performs better in Chile remains open. Policy decisions regarding health service
      provision requires more evidence explaining differences by ownership. Better
      controls for health risk and hospital characteristics are suggested to address
      these differences in hospital performance.

PMID- 25759456
TI  - Can mobile phone messages to drug sellers improve treatment of childhood
      diarrhoea?--A randomized controlled trial in Ghana.
AB  - Oral rehydration solution (ORS) and zinc are the recommended treatment in
      developing countries for the management of uncomplicated diarrhoea in children
      under five (World Health Organization and UNICEF 2004). However, drug sellers
      often recommend costly and unnecessary treatments instead. This article reports
      findings from an experiment to encourage licensed chemical sellers (LCS) in Ghana
      to recommend ORS and zinc for the management of childhood diarrhoea. The
      intervention consisted of mobile phone text messages (Short Message Service or
      SMS) sent to a randomly assigned group of LCS who had been trained on the
      diarrhoea management protocols recommended by the World Health Organization
      (WHO). The SMS campaign comprised informational messages and interactive quizzes
      sent over an 8-week period. The study measured the impact of the SMS messages on
      both reported and actual practices. Analysis of data from both face-to-face
      interviews and mystery client visits shows that the SMS intervention improved
      providers' self-reported practices but not their actual practices. The study also
      finds that actual practices deviate substantially from reported practices. 

PMID- 25759457
TI  - Regulating the for-profit private health sector: lessons from East and Southern
      Africa.
AB  - International evidence shows that, if poorly regulated, the private health sector
      may lead to distortions in the type, quantity, distribution, quality and price of
      health services, as well as anti-competitive behaviour. This article provides an
      overview of legislation governing the for-profit private health sector in East
      and Southern Africa. It identifies major implementation problems and suggests
      strategies Ministries of Health could adopt to regulate the private sector more
      effectively and in line with key public health objectives. This qualitative study
      was based on a document review of existing legislation in the region, and seven
      semi-structured interviews with individuals selected purposively on the basis of
      their experience in policymaking and legislation. Legislation was categorized
      according to its objectives and the level at which it operates. A thematic
      content analysis was conducted on interview transcripts. Most legislation focuses
      on controlling the entry of health professionals and organizations into the
      market. Most countries have not developed adequate legislation around behaviour
      following entry. Generally the type and quality of services provided by private
      practitioners and facilities are not well-regulated or monitored. Even where
      there is specific health insurance regulation, provisions seldom address open
      enrolment, community rating and comprehensive benefit packages (except in South
      Africa). There is minimal control of prices. Several countries are updating and
      improving legislation although, in most cases, this is without the benefit of an
      overarching policy on the private sector, or reference to wider public health
      objectives. Policymakers in the East and Southern African region need to embark
      on a programme of action to strengthen regulatory frameworks and instruments in
      relation to private health care provision and insurance. They should not
      underestimate the power of the private health sector to undermine efforts for
      increased regulation. Consequently they should conduct careful stakeholder
      analyses and build alliances to help drive through reform. 

PMID- 25759459
TI  - Intact bone vitality and increased accumulation of nonmineralized bone matrix in
      biopsy specimens of juvenile osteochondritis dissecans: a histological analysis.
AB  - BACKGROUND: Although commonly proposed to be the starting point of juvenile
      osteochondritis dissecans (JOCD), avascular osteonecrosis (AVN) has been an
      inconsistent finding in histological studies. Analysis of early-stage lesions is
      required to elucidate the origins of OCD and justify proper treatment. PURPOSE:
      To analyze histological sections of JOCD lesions with special emphasis on bone
      vitality. STUDY DESIGN: Cross-sectional study; Level of evidence, 3. METHODS: Of
      64 patients with 74 JOCD lesions (20 females, mean age, 11.4 years; 44 males,
      mean age, 12.7 years), 34 required surgery because of lesion instability or
      failed nonoperative treatment. From 9 patients, 11 histological specimens were
      obtained. Lesions were classified according to the International Cartilage Repair
      Society (ICRS). Two additional histological control sections were harvested from
      children without JOCD manifestation. Undecalcified histological sections were
      histomorphometrically analyzed. To analyze the skeletal health of the patients,
      biochemical analyses with special emphasis on bone metabolism were performed.
      RESULTS: Histologically, no osteonecrosis was visible in any of the cases.
      Osteocyte distribution was similar among OCD lesions and controls. ICRS OCD I
      lesions (n = 6) showed no intralesional separation. In ICRS OCD II and III
      lesions (n = 5), there was a subchondral fracture concomitant with histological
      characteristics of active repair mechanism (increased bone formation: osteoid
      volume P = .008, osteoblast number P = .046; resorption: osteoclast number P =
      .005; and tissue fibrosis compared with controls). Instead, in ICRS OCD I
      lesions, subchondral osteoid volume (P = .010) and osteoblast number (P = .046)
      were significantly increased compared with controls; however, no active repair
      mechanisms (no increased bone resorption or fibrous tissue) were detected,
      suggesting a focal lack of mineralization. Fifty-seven of 64 patients (89.1%)
      showed a vitamin D deficiency. The median vitamin D serum level of the patients
      with ICRS OCD I lesions was 13.6 ug/L. CONCLUSION: In the present study,
      osteonecrosis was not found in histological specimens of JOCD. As a secondary
      finding, focal accumulations of nonmineralized bone matrix indicating a lack of
      mineralization in ICRS OCD I lesions were revealed. This finding correlated with
      a low level of vitamin D in the affected children.

PMID- 25759458
TI  - Cardiac structure and function across the glycemic spectrum in elderly men and
      women free of prevalent heart disease: the Atherosclerosis Risk In the Community
      study.
AB  - BACKGROUND: Individuals with diabetes mellitus and pre-diabetes mellitus are at
      particularly high risk of incident heart failure or death, even after accounting
      for known confounders. Nevertheless, the extent of impairments in cardiac
      structure and function in elderly individuals with diabetes mellitus and pre
      diabetes mellitus is not well known. We aimed to assess the relationship between
      echocardiographic measures of cardiac structure and function and dysglycemia.
      METHODS AND RESULTS: We assessed measures of cardiac structure and function in
      4419 participants without prevalent coronary heart disease or heart failure who
      attended the Atherosclerosis Risk In the Community (ARIC) visit 5 examination
      (2011-2013) and underwent transthoracic echocardiography (age, 75+/-6 years; 61%
      women, 23% black). Subjects were grouped across the dysglycemia spectrum as
      normal (39%), pre-diabetes mellitus (31%), or diabetes mellitus (30%) based on
      medical history, antidiabetic medication use, and glycated hemoglobin levels.
      Glycemic status was related to measures of cardiac structure and function.
      Worsening dysglycemia was associated with increased left ventricular mass, worse
      diastolic function, and subtle reduction in left ventricular systolic function
      (P<=0.01 for all). For every 1% higher glycated hemoglobin, left ventricular mass
      was higher by 3.0 g (95% confidence interval, 1.5-4.6 g), E/E' by 0.5 (95%
      confidence interval, 0.4-0.7), and global longitudinal strain by 0.3% (95%
      confidence interval, 0.2-0.4) in multivariable analyses. CONCLUSIONS: In a large
      contemporary biracial cohort of elderly subjects without prevalent cardiovascular
      disease or heart failure, dysglycemia was associated with subtle and subclinical
      alterations of cardiac structure, and left ventricular systolic and diastolic
      function. It remains unclear whether these are sufficient to explain the
      heightened risk of heart failure in individuals with diabetes mellitus.

PMID- 25759460
TI  - East asian variant of aldehyde dehydrogenase 2 is associated with coronary
      spastic angina: possible roles of reactive aldehydes and implications of alcohol
      flushing syndrome.
AB  - BACKGROUND: Coronary spastic angina (CSA) is a common disease among East Asians,
      including Japanese. The prevalence of alcohol flushing syndrome associated with
      deficient activity of the variant aldehyde dehydrogenase 2 (ALDH2*2) genotype is
      prevalent among East Asians. We examined whether CSA is associated with the
      ALDH2*2 genotype in Japanese. METHODS AND RESULTS: The study subjects consisted
      of 202 patients in whom intracoronary injection of acetylcholine was performed by
      angiography on suspicion of CSA (119 men and 83 women; mean age, 66.2+/-11.4
      years). They were divided into CSA (112 patients) and control groups (90
      patients). ALDH2 genotyping was performed by the direct application of the TaqMan
      polymerase chain reaction system on dried whole blood. Clinical and laboratory
      data were examined using conventional methods. The frequencies of male sex,
      ALDH2*2 genotype carriers, alcohol flushing syndrome, tobacco smoking, and the
      plasma level of uric acid were higher (P<0.001, P<0.001, P<0.001, P<0.001, and
      P=0.007, respectively) and the plasma high-density lipoprotein cholesterol levels
      were lower (P<0.001) in the CSA group than in the control group. The
      multivariable logistic regression analysis revealed that ALDH2*2 genotype and
      smoking were significantly associated with CSA (P<0.001 and P=0.024,
      respectively). CONCLUSIONS: East Asian variant ALDH2*2 genotypes and, hence,
      deficient ALDH2 activity were associated with CSA in Japanese. These data support
      further investigation of treatment targeting aldehydes for CSA.

PMID- 25759461
TI  - Handgrip Strength Predicts Difficult Weaning But Not Extubation Failure in
      Mechanically Ventilated Subjects.
AB  - BACKGROUND: Muscle weakness, defined by the Medical Research Council scale, has
      been associated with delay in mechanical ventilation weaning. In this study, we
      evaluated handgrip strength as a prediction tool in weaning outcome. METHODS:
      This was a 1-y prospective study in 2 ICUs in 2 university hospitals. Adult
      patients who were on mechanical ventilation for at least 48 h and eligible for
      mechanical ventilation weaning were screened for inclusion. Handgrip strength was
      evaluated using a handheld dynamometer before each spontaneous breathing trial
      (SBT). Attending physicians were unaware of handgrip strength and decided on
      extubation according to guidelines. RESULTS: Eighty-four subjects were included
      (median age 66 [53-79] y, with a median Simplified Acute Physiology Score II of
      49 [37-63]). At the first evaluation, median handgrip strength was significantly
      associated with weaning outcome as defined by international guidelines: simple
      (20 [12-26] kg), difficult (12 [6-21] kg), or prolonged (6 [3-11] kg) weaning (P
      = .008). Time to liberation from mechanical ventilation and ICU stay were
      significantly longer for subjects classified as having muscle weakness according
      to the handgrip strength-derived definition (P = .02 and P = .03, respectively).
      In multivariate analysis, known history of COPD (odds ratio [OR] 5.48, 95% CI
      1.44-20.86, P = .01), sex (OR 6.16, 95% CI 1.64-23.16, P = .007), and handgrip
      strength at the first SBT (OR 0.89, 95% CI 0.85-0.97, P = .004) were
      significantly associated with difficult or prolonged weaning. Extubation failure,
      as defined by re-intubation or unscheduled noninvasive ventilation within 48 h
      after extubation, occurred 14 times after 92 attempts, leading to an extubation
      failure rate of 15%. No association was found between handgrip strength and
      extubation outcome. CONCLUSIONS: Muscle weakness, assessed by handgrip strength,
      is associated with difficult or prolonged mechanical ventilation weaning and ICU
      stay, but not with extubation outcome.

PMID- 25759462
TI  - Prolonged Oxygen Kinetics During Constant Workload Submaximal Exercise Is
      Associated With Disease Severity in Adult Subjects With Cystic Fibrosis.
AB  - BACKGROUND: The goal of this study was to explore the relation between oxygen
      kinetics during constant work load submaximal cardiopulmonary exercise test
      (CPET) and disease severity in adult subjects with cystic fibrosis. METHODS:
      Fourteen adult subjects with cystic fibrosis (CF; 8 males, 22 +/- 4 y old) and a
      mean Schwachman score of 73 +/- 11 and 10 healthy individuals (5 males, 29 +/- 4
      y old) underwent pulmonary function tests at rest, maximal and constant work load
      submaximal CPET on a cycloergometer. Breath-by-breath analysis was used for
      measuring oxygen kinetic parameters and the time constant (tau), expressing phase
      2 of submaximal CPET. RESULTS: Subjects with CF had a significantly prolonged tau
      compared with healthy subjects (42.3 +/- 21.5 vs. 29.3 +/- 6.4, s, P < .05). The
      tau during phase 2 was inversely correlated with FEV1(% pred) (r = -0.77, P =
      .001), breathing reserve (r = -0.74, P = .003), VO2peak (r = -0.53, P = .049),
      VO2/t slope (r = -0.58, P = .03), and Schwachman score (r = -0.80, P = .001). In
      a multivariate regression model including all the above variables, the Schwachman
      score (beta = -0.697, P = .002) emerged as independent predictor of tau (R2 =
      0.719, P = .001). CONCLUSIONS: We conclude that adult subjects with CF present
      significant prolonged oxygen kinetics during constant work load submaximal
      exercise in relation to disease severity. Thus, submaximal exercise should be
      considered the preferable CPET choice in adult patients with severe CF.

PMID- 25759463
TI  - Utility and Safety of Endoscopic Ultrasound With Bronchoscope-Guided Fine-Needle
      Aspiration in Mediastinal Lymph Node Sampling: Systematic Review and Meta
      Analysis.
AB  - BACKGROUND: The use of endoscopic ultrasound with bronchoscope-guided fine-needle
      aspiration (EUS-B-FNA) has been described in the evaluation of mediastinal
      lymphadenopathy. Herein, we conduct a meta-analysis to estimate the overall
      diagnostic yield and safety of EUS-B-FNA combined with endobronchial ultrasound
      guided transbronchial needle aspiration (EBUS-TBNA), in the diagnosis of
      mediastinal lymphadenopathy. METHODS: The PubMed and EmBase databases were
      searched for studies reporting the outcomes of EUS-B-FNA in diagnosis of
      mediastinal lymphadenopathy. The study quality was assessed using the QualSyst
      tool. The yield of EBUS-TBNA alone and the combined procedure (EBUS-TBNA and EUS
      B-FNA) were analyzed by calculating the sensitivity, specificity, positive
      likelihood ratio, negative likelihood ratio, and diagnostic odds ratio for each
      study, and pooling the study results using a random effects model. Heterogeneity
      and publication bias were assessed for individual outcomes. The additional
      diagnostic gain of EUS-B-FNA over EBUS-TBNA was calculated using proportion meta
      analysis. RESULTS: Our search yielded 10 studies (1,080 subjects with mediastinal
      lymphadenopathy). The sensitivity of the combined procedure was significantly
      higher than EBUS-TBNA alone (91% vs 80%, P = .004), in staging of lung cancer (4
      studies, 465 subjects). The additional diagnostic gain of EUS-B-FNA over EBUS
      TBNA was 7.6% in the diagnosis of mediastinal adenopathy. No serious complication
      of EUS-B-FNA procedure was reported. Clinical and statistical heterogeneity was
      present without any evidence of publication bias. CONCLUSIONS: Combining EBUS
      TBNA and EUS-B-FNA is an effective and safe method, superior to EBUS-TBNA alone,
      in the diagnosis of mediastinal lymphadenopathy. Good quality randomized
      controlled trials are required to confirm the results of this systematic review.

PMID- 25759464
TI  - Serum Nuclear Magnetic Resonance Spectroscopy: One More Step toward Clinical
      Utility.

PMID- 25759465
TI  - Continuous age- and sex-adjusted reference intervals of urinary markers for
      cerebral creatine deficiency syndromes: a novel approach to the definition of
      reference intervals.
AB  - BACKGROUND: Urinary concentrations of creatine and guanidinoacetic acid divided
      by creatinine are informative markers for cerebral creatine deficiency syndromes
      (CDSs). The renal excretion of these substances varies substantially with age and
      sex, challenging the sensitivity and specificity of postanalytical
      interpretation. METHODS: Results from 155 patients with CDS and 12 507 reference
      individuals were contributed by 5 diagnostic laboratories. They were binned into
      104 adjacent age intervals and renormalized with Box-Cox transforms (Xi).
      Estimates for central tendency (MU) and dispersion (sigma) of Xi were obtained
      for each bin. Polynomial regression analysis was used to establish the age
      dependence of both MU[log(age)] and sigma[log(age)]. The regression residuals
      were then calculated as z-scores = {Xi - MU[log(age)]}/sigma[log(age)]. The
      process was iterated until all z-scores outside Tukey fences +/-3.372 were
      identified and removed. Continuous percentile charts were then calculated and
      plotted by retransformation. RESULTS: Statistically significant and biologically
      relevant subgroups of z-scores were identified. Significantly higher marker
      values were seen in females than males, necessitating separate reference
      intervals in both adolescents and adults. Comparison between our reconstructed
      reference percentiles and current standard age-matched reference intervals
      highlights an underlying risk of false-positive and false-negative events at
      certain ages. CONCLUSIONS: Disease markers depending strongly on covariates such
      as age and sex require large numbers of reference individuals to establish
      peripheral percentiles with sufficient precision. This is feasible only through
      collaborative data sharing and the use of appropriate statistical methods. Broad
      application of this approach can be implemented through freely available Web
      based software.

PMID- 25759466
TI  - Copy number assessment by competitive PCR with limiting deoxynucleotide
      triphosphates and high-resolution melting.
AB  - BACKGROUND: DNA copy number variation is associated with genetic disorders and
      cancer. Available methods to discern variation in copy number are typically
      costly, slow, require specialized equipment, and/or lack precision. METHODS:
      Multiplex PCR with different primer pairs and limiting deoxynucleotide
      triphosphates (dNTPs) (3-12 MUmol/L) were used for relative quantification and
      copy number assessment. Small PCR products (50-121 bp) were designed with 1
      melting domain, well-separated Tms, minimal internal sequence variation, and no
      common homologs. PCR products were displayed as melting curves on derivative
      plots and normalized to the reference peak. Different copy numbers of each target
      clustered together and were grouped by unbiased hierarchical clustering. RESULTS:
      Duplex PCR of a reference gene and a target gene was used to detect copy number
      variation in chromosomes X, Y, 13, 18, 21, epidermal growth factor receptor
      (EGFR), survival of motor neuron 1, telomeric (SMN1), and survival of motor
      neuron 2, centromeric (SMN2). Triplex PCR was used for X and Y and CFTR exons 2
      and 3. Blinded studies of 50 potential trisomic samples (13, 18, 21, or normal)
      and 50 samples with potential sex chromosome abnormalities were concordant to
      karyotyping, except for 2 samples that were originally mosaics that displayed a
      single karyotype after growth. Large cystic fibrosis transmembrane conductance
      regulator (ATP-binding cassette sub-family C, member 7) (CFTR) deletions, EGFR
      amplifications, and SMN1 and SMN2 copy number assessments were also demonstrated.
      Under ideal conditions, copy number changes of 1.11-fold or lower could be
      discerned with CVs of about 1%. CONCLUSIONS: Relative quantification by
      restricting the dNTP concentration with melting curve display is a simple and
      precise way to assess targeted copy number variation.

PMID- 25759467
TI  - Intact neuronal function in Rheb1 mutant mice: implications for TORC1-based
      treatments.
AB  - Target of rapamycin complex 1 (TORC1) is an important regulator of neuronal
      function. However, whereas a modest activation of the TORC1 signaling pathway has
      been shown to affect synaptic plasticity, learning and memory, the effect of
      TORC1 hypo-activation is less clear. This knowledge is particularly important
      since TORC1 inhibitors may hold great promise for treating a variety of
      disorders, including developmental disorders, aging-related disorders, epilepsy
      and cancer. Such treatments are likely to be long lasting and could involve
      treating young children. Hence, it is pivotal that the effects of sustained TORC1
      inhibition on brain development and cognitive function are determined. Here, we
      made use of constitutive and conditional Rheb1 mutant mice to study the effect of
      prolonged and specific reduction in the TORC1 pathway. We show that Rheb1 mutant
      mice show up to 75% reduction in TORC1 signaling, but develop normally and show
      intact synaptic plasticity and hippocampus-dependent learning and memory. We
      discuss our findings in light of current literature in which the effect of
      pharmacological inhibition of TORC1 is studied in the context of synaptic
      plasticity and learning. We conclude that in contrast to TORC1 hyper-activity,
      cognitive function is not very sensitive to sustained and specific down
      regulation of TORC1 activity. 

PMID- 25759468
TI  - Genome-wide profiling of polyadenylation sites reveals a link between selective
      polyadenylation and cancer metastasis.
AB  - Alternative polyadenylation (APA) is an important post-transcriptional
      modification implicated in many diseases, including cancer. Although extensively
      characterized, the functional consequence of APA modulation on tumorigenesis
      remains elusive. Here, we developed a deep sequencing-based approach that
      specifically profiles 3' termini of polyadenylated RNAs (herein termed 3T-seq)
      and analyzed APA events in two gastric cancer cell lines and one non-transformed
      counterpart. Overall, we identified >28 000 poly(A) sites, 70% of which are
      potentially novel. Further, we observed widespread APA-mediated 3' UTR shortening
      of 513 genes (false discovery rate < 0.05) across gastric cancer genome. We
      characterized one of these genes, NET1, in detail and found that the shortening
      of NET1 3' UTR significantly enhances transcriptional activity. Moreover, the
      NET1 isoform with short 3' UTR promotes cellular migration and invasion in vitro.
      Collectively, our work provides an effective approach for genome-wide APA site
      profiling and reveals a link between APA modulation and gastric cancer
      metastasis. 

PMID- 25759470
TI  - Mothers know best: redirecting adolescent reward sensitivity toward safe behavior
      during risk taking.
AB  - Despite being one of the healthiest developmental periods, morbidity and
      mortality rates increase dramatically during adolescence, largely due to
      preventable, risky behaviors. Heightened reward sensitivity, coupled with
      ineffective cognitive control, has been proposed to underlie adolescents' risk
      taking. In this study, we test whether reward sensitivity can be redirected to
      promote safe behavior. Adolescents completed a risk-taking task in the presence
      of their mother and alone during fMRI. Adolescents demonstrated reduced risk
      taking behavior when their mothers were present compared with alone, which was
      associated with greater recruitment of the ventrolateral prefrontal cortex
      (VLPFC) when making safe decisions, decreased activation in the ventral striatum
      following risky decisions and greater functional coupling between the ventral
      striatum and VLPFC when making safe decisions. Importantly, the very same neural
      circuitry (i.e. ventral striatum) that has been linked to greater risk-taking can
      also be redirected toward thoughtful, more deliberative and safe decisions. 

PMID- 25759469
TI  - A mutation in FRIZZLED2 impairs Wnt signaling and causes autosomal dominant
      omodysplasia.
AB  - Autosomal dominant omodysplasia is a rare skeletal dysplasia characterized by
      short humeri, radial head dislocation, short first metacarpals, facial
      dysmorphism and genitourinary anomalies. We performed next-generation whole-exome
      sequencing and comparative analysis of a proband with omodysplasia, her
      unaffected parents and her affected daughter. We identified a de novo mutation in
      FRIZZLED2 (FZD2) in the proband and her daughter that was not found in unaffected
      family members. The FZD2 mutation (c.1644G>A) changes a tryptophan residue at
      amino acid 548 to a premature stop (p.Trp548*). This altered protein is still
      produced in vitro, but we show reduced ability of this mutant form of FZD2 to
      interact with its downstream target DISHEVELLED. Furthermore, expressing the
      mutant form of FZD2 in vitro is not able to facilitate the cellular response to
      canonical Wnt signaling like wild-type FZD2. We therefore conclude that the
      FRIZZLED2 mutation is a de novo, novel cause for autosomal dominant omodysplasia.

PMID- 25759471
TI  - EEG correlates of impaired self-other integration during joint-task performance
      in schizophrenia.
AB  - Deficits in a wide variety of social cognitive processes are well established in
      schizophrenia. However, research focusing on actual interacting individuals is
      surprisingly scarce. Problems in low-level processes such as self-other
      integration may importantly underlie often-reported higher-level deficits. The
      current study aimed at measuring possible disturbances in self-other integration
      in schizophrenia using both behavioral and event-related potential (ERP)
      measures. Sixteen healthy controls and fifteen schizophrenia patients performed a
      social Simon task in both a joint and an individual setting. Behaviorally,
      patients showed general slower reaction times, but comparable self-other
      integration as reflected in the social Simon effect. The ERP results for the
      healthy controls revealed increased no-go P3 amplitudes in the joint compared
      with the individual setting. Crucially, patients did not show this increase in no
      go P3 amplitude. In line with previous research, the present ERP findings
      demonstrate that healthy volunteers needed more effort to inhibit their responses
      in the joint compared with the individual setting. Patients however, showed
      altered self-other integration when they had to withhold their responses while
      their co-actor had to act. These outcomes indicate that schizophrenia patients
      have deficits in low-level processes required for successful joint action. 

PMID- 25759472
TI  - Emotionally anesthetized: media violence induces neural changes during emotional
      face processing.
AB  - Media violence exposure causes increased aggression and decreased prosocial
      behavior, suggesting that media violence desensitizes people to the emotional
      experience of others. Alterations in emotional face processing following exposure
      to media violence may result in desensitization to others' emotional states. This
      study used scalp electroencephalography methods to examine the link between
      exposure to violence and neural changes associated with emotional face
      processing. Twenty-five participants were shown a violent or nonviolent film clip
      and then completed a gender discrimination stop-signal task using emotional
      faces. Media violence did not affect the early visual P100 component; however,
      decreased amplitude was observed in the N170 and P200 event-related potentials
      following the violent film, indicating that exposure to film violence leads to
      suppression of holistic face processing and implicit emotional processing.
      Participants who had just seen a violent film showed increased frontal N200/P300
      amplitude. These results suggest that media violence exposure may desensitize
      people to emotional stimuli and thereby require fewer cognitive resources to
      inhibit behavior. 

PMID- 25759475
TI  - Chlamydia screening is not cost-effective at low participation rates: evidence
      from a repeated register-based implementation study in The Netherlands.
AB  - OBJECTIVE: In three pilot regions of The Netherlands, all 16-29 year olds were
      invited to participate in three annual rounds of Chlamydia screening. The aim of
      the present study is to evaluate the cost-effectiveness of repeated Chlamydia
      screening, based on empirical data. METHODS: A mathematical model was employed to
      estimate the influence of repeated screening on prevalence and incidence of
      Chlamydial infection. A model simulating the natural history of Chlamydia was
      combined with cost and utility data to estimate the number of major outcomes and
      quality-adjusted life-years (QALYs) associated with Chlamydia. Six screening
      scenarios (16-29 years annually; 16-24 years annually; women only; biennial
      screening; biennial screening women only; screening every five years) were
      compared with no screening in two sexual networks, representing both lower
      ('national network') and higher ('urban network') baseline prevalence.
      Incremental cost-effectiveness ratios (ICERs) for the different screening
      scenarios were estimated. Uncertainty and sensitivity analyses were performed.
      RESULTS: In all scenarios and networks, cost per major outcome averted are above
      ?5000. Cost per QALY are at least ?50,000. The default scenario as piloted in the
      Netherlands was least cost-effective, with ICERs of ?232,000 in the national and
      ?145,000 in the urban sexual network. Results were robust in sensitivity
      analyses. CONCLUSIONS: It is unlikely that repeated rounds of Chlamydia screening
      will be cost-effective. Only at high levels of willingness to pay for a QALY
      (>?50,000) screening may be more cost-effective than no screening.

PMID- 25759473
TI  - The promise of biological markers for treatment response in first-episode
      psychosis: a systematic review.
AB  - Successful treatment of first-episode psychosis is one of the major factors that
      impacts long-term prognosis. Currently, there are no satisfactory biological
      markers (biomarkers) to predict which patients with a first-episode psychosis
      will respond to which treatment. In addition, a non-negligible rate of patients
      does not respond to any treatment or may develop side effects that affect
      adherence to the treatments as well as negatively impact physical health. Thus,
      there clearly is a pressing need for defining biomarkers that may be helpful to
      predict response to treatment and sensitivity to side effects in first-episode
      psychosis. The present systematic review provides (1) trials that assessed
      biological markers associated with antipsychotic response or side effects in
      first-episode psychosis and (2) potential biomarkers associated with biological
      disturbances that may guide the choice of conventional treatments or the
      prescription of innovative treatments. Trials including first-episode psychoses
      are few in number. Most of the available data focused on pharmacogenetics markers
      with so far only preliminary results. To date, these studies yielded-beside
      markers for metabolism of antipsychotics-no or only a few biomarkers for response
      or side effects, none of which have been implemented in daily clinical practice.
      Other biomarkers exploring immunoinflammatory, oxidative, and hormonal
      disturbances emerged as biomarkers of first-episode psychoses in the last
      decades, and some of them have been associated with treatment response. In
      addition to pharmacogenetics, further efforts should focus on the association of
      emergent biomarkers with conventional treatments or with innovative therapies
      efficacy, where some preliminary data suggest promising results. 

PMID- 25759476
TI  - Active recall to increase HIV and STI testing: a systematic review.
AB  - BACKGROUND: Active recall can improve reattendance rates and could increase
      retesting rates and detection of HIV and sexually transmitted infections (STIs),
      but the best strategy remains uncertain. METHODS: We conducted a systematic
      review and meta-analysis of active recall for HIV and/or STI testing. We searched
      six electronic databases using terms for HIV, STIs, tests and active recall
      (defined as a reminder to retest for HIV/STIs) for randomised, non-randomised and
      observational English-language studies published between 1983 and 2013. Outcomes
      included reattendance/retesting rate and STI diagnosis at follow-up. RESULTS: Of
      5634 papers identified, 17 met the inclusion criteria. Of the 14 comparative
      studies, all but one demonstrated higher reattendance/retesting rates in the
      intervention group, but the range was wide (17.5-89%). Meta-analysis of nine RCTs
      found reattendance/retesting rates were significantly higher in the intervention
      versus control groups (pooled OR 2.42 (95% CI 1.84 to 3.19)). In a subgroup
      analysis, home sampling increased retesting compared with clinic testing (pooled
      OR 2.20 (95% CI 1.65 to 2.94)). In observational studies SMS reminders increased
      retesting compared with standard clinic care (pooled OR 2.19 (95% CI 1.46 to
      3.29)), but study estimates were highly heterogeneous (I(2)=94%, p<0.001).
      CONCLUSIONS: Active recall interventions are associated with higher
      reattendance/retesting rates for HIV/STI. Although home sampling and SMS
      reminders were associated with higher reattendance/retesting rates in most
      studies, evidence is limited by the heterogeneity of interventions and control
      groups and the quality of studies. Further work is needed to explore which active
      recall modality is clinically cost-effective and acceptable for HIV/STI
      screening.

PMID- 25759474
TI  - Systematic Integration of Brain eQTL and GWAS Identifies ZNF323 as a Novel
      Schizophrenia Risk Gene and Suggests Recent Positive Selection Based on
      Compensatory Advantage on Pulmonary Function.
AB  - Genome-wide association studies have identified multiple risk variants and loci
      that show robust association with schizophrenia. Nevertheless, it remains unclear
      how these variants confer risk to schizophrenia. In addition, the driving force
      that maintains the schizophrenia risk variants in human gene pool is poorly
      understood. To investigate whether expression-associated genetic variants
      contribute to schizophrenia susceptibility, we systematically integrated brain
      expression quantitative trait loci and genome-wide association data of
      schizophrenia using Sherlock, a Bayesian statistical framework. Our analyses
      identified ZNF323 as a schizophrenia risk gene (P = 2.22*10(-6)). Subsequent
      analyses confirmed the association of the ZNF323 and its expression-associated
      single nucleotide polymorphism rs1150711 in independent samples (gene-expression:
      P = 1.40*10(-6); single-marker meta-analysis in the combined discovery and
      replication sample comprising 44123 individuals: P = 6.85*10(-10)). We found that
      the ZNF323 was significantly downregulated in hippocampus and frontal cortex of
      schizophrenia patients (P = .0038 and P = .0233, respectively). Evidence for
      pleiotropic effects was detected (association of rs1150711 with lung function and
      gene expression of ZNF323 in lung: P = 6.62*10(-5) and P = 9.00*10(-5),
      respectively) with the risk allele (T allele) for schizophrenia acting as
      protective allele for lung function. Subsequent population genetics analyses
      suggest that the risk allele (T) of rs1150711 might have undergone recent
      positive selection in human population. Our findings suggest that the ZNF323 is a
      schizophrenia susceptibility gene whose expression may influence schizophrenia
      risk. Our study also illustrates a possible mechanism for maintaining
      schizophrenia risk variants in the human gene pool. 

PMID- 25759477
TI  - Conformational activation of visual rhodopsin in native disc membranes.
AB  - Rhodopsin is the G protein-coupled receptor (GPCR) that serves as a dim-light
      receptor for vision in vertebrates. We probed light-induced conformational
      changes in rhodopsin in its native membrane environment at room temperature using
      time-resolved wide-angle x-ray scattering. We observed a rapid conformational
      transition that is consistent with an outward tilt of the cytoplasmic portion of
      transmembrane helix 6 concomitant with an inward movement of the cytoplasmic
      portion of transmembrane helix 5. These movements were considerably larger than
      those reported from the basis of crystal structures of activated rhodopsin,
      implying that light activation of rhodopsin involves a more extended
      conformational change than was previously suggested. 

PMID- 25759479
TI  - Plasma membrane-associated platforms: dynamic scaffolds that organize membrane
      associated events.
AB  - Specialized regions of the plasma membrane dedicated to diverse cellular
      processes, such as vesicle exocytosis, extracellular matrix remodeling, and cell
      migration, share a few cytosolic scaffold proteins that associate to form large
      plasma membrane-associated platforms (PMAPs). PMAPs organize signaling events and
      trafficking of membranes and molecules at specific membrane domains. On the basis
      of the intrinsic disorder of the proteins constituting the core of these PMAPs
      and of the dynamics of these structures at the periphery of motile cells, we
      propose a working model for the assembly and turnover of these platforms. 

PMID- 25759478
TI  - Phosphorylation of eIF2alpha triggered by mTORC1 inhibition and PP6C activation
      is required for autophagy and is aberrant in PP6C-mutated melanoma.
AB  - Amino acid deprivation promotes the inhibition of the kinase complex mTORC1
      (mammalian target of rapamycin complex 1) and activation of the kinase GCN2
      (general control nonrepressed 2). Signaling pathways downstream of both kinases
      have been thought to independently induce autophagy. We showed that these two
      amino acid-sensing systems are linked. We showed that pharmacological inhibition
      of mTORC1 led to activation of GCN2 and phosphorylation of the eukaryotic
      initiation factor 2alpha (eIF2alpha) in a mechanism dependent on the catalytic
      subunit of protein phosphatase 6 (PP6C). Autophagy induced by pharmacological
      inhibition of mTORC1 required PP6C, GCN2, and eIF2alpha phosphorylation. Although
      some of the PP6C mutants found in melanoma did not form a strong complex with PP6
      regulatory subunits and were rapidly degraded, these mutants paradoxically
      stabilized PP6C encoded by the wild-type allele and increased eIF2alpha
      phosphorylation. Furthermore, these PP6C mutations were associated with increased
      autophagy in vitro and in human melanoma samples. Thus, these data showed that
      GCN2 activation and phosphorylation of eIF2alpha in response to mTORC1 inhibition
      are necessary for autophagy. Additionally, we described a role for PP6C in this
      process and provided a mechanism for PP6C mutations associated with melanoma. 

PMID- 25759480
TI  - Surgical strategy for Kommerell's diverticulum with aberrant subclavian artery.

PMID- 25759481
TI  - Surgical strategy for Kommerell's diverticulum with aberrant subclavian artery:
      reply.

PMID- 25759482
TI  - Reverse U aortotomy (Kirali incision) for aortic valve replacement.
AB  - The presence of patent vein grafts on the proximal aorta may cause technical
      difficulties during reoperations for aortic valve replacement after previous
      coronary artery bypass surgery. A 65-year-old man underwent reoperation for
      aortic valve replacement two years after his first open heart surgery (valve
      sparing aortic root replacement and aorta-right coronary artery saphenous vein
      graft). The aortotomy incision was started approximately 2 cm above the proximal
      anastomosis and continued down at both sides until the prosthetic graft. The
      reverse U aortotomy prevents unnecessary and risky manipulations of proximal
      anastomoses, provides perfect exposure, and can be used securely during
      reoperative aortic valve surgery. 

PMID- 25759483
TI  - CT and microbiologic follow-up in primary multidrug-resistant pulmonary
      tuberculosis.
AB  - BACKGROUND: Little attention has been paid to the initial and follow-up computed
      tomography (CT) features in primary multi-drug resistant tuberculosis (pMDR-TB)
      setting. PURPOSE: To describe serial CT findings and clinical course of pMDR-TB
      with antibiotic treatment. MATERIAL AND METHODS: For the last 10 years, 340 MDR
      TB patients were managed in a tertiary referral hospital. Among them, we included
      44 (27 men, 17 women; mean age, 40 years; age range, 20-81 years) pMDR-TB
      patients; 37 treated with chemotherapy only and seven treated with medical
      therapy plus surgery. CT findings were evaluated regarding tree-in-bud sign,
      acinar nodule, peribronchial, segmental or lobar consolidation and cavity, and
      their extent. Sputum negative conversion rates and serial CT scores were
      assessed. To compare changes in disease extent between initial and follow-up CT
      studies, paired t-test was performed. RESULTS: Two most frequent patterns of lung
      abnormality were tree-in-bud sign (37 of 44, 84.1%) and acinar nodule (41 of 44,
      93.2%). Among 37 patients treated with chemotherapy only, 36 showed negative
      sputum conversion within 3 months after second-line drug commencement, maintained
      for >12 months. The other seven undergoing surgery during medical treatment
      showed excellent outcome with negative conversion achieved within one month after
      surgery and maintained for >12 months. CT scores showed significant decrease on
      serial CT studies (P < 0.001) in all. CONCLUSION: In pMDR-TB, two most frequent
      abnormal CT patterns are tree-in-bud sign and acinar nodule. In 98% of patients,
      negative sputum conversion is achieved, and CT score also shows decrease in
      extent after TB chemotherapy.

PMID- 25759484
TI  - Prognostic significance of the concomitant existence of lymphovascular and
      perineural invasion in locally advanced gastric cancer patients who underwent
      curative gastrectomy and adjuvant chemotherapy.
AB  - OBJECTIVE: In this study, we evaluated the prognostic significance of the
      concomitant existence of lymphovascular invasion and perineural invasion in
      patients with advanced gastric cancer. METHODS: A total of 206 consecutive
      patients with Stage II or III gastric cancer who underwent curative D2
      gastrectomy and adjuvant chemotherapy from April 2004 to December 2011 were
      analyzed. Patients were classified into four groups according to the presence (+)
      or absence (-) of lymphovascular invasion and perineural invasion: lymphovascular
      invasion-/perineural invasion- (n = 33), lymphovascular invasion+/perineural
      invasion- (n = 31), lymphovascular invasion-/perineural invasion+ (n = 54) and
      lymphovascular invasion+/perineural invasion+ (n = 88). RESULTS: A total of 136
      patients (66.0%) received 5-fluorouracil plus cisplatin adjuvant chemotherapy and
      70 patients (34.0%) received TS-1. During the median follow-up period of 35.18
      months, the median disease-free survival times for lymphovascular invasion
      /perineural invasion-, lymphovascular invasion+/perineural invasion- and
      lymphovascular invasion-/perineural invasion+ were not reached at the time of
      analysis; however, median disease-free survival for lymphovascular
      invasion+/perineural invasion+ was the worst (36.73 months, P = 0.001). The
      median overall survival in the four groups was also not reached at the time of
      analysis; however, median overall survival with lymphovascular
      invasion+/perineural invasion+ was the poorest (P = 0.002). In a multivariate
      analysis, lymphovascular invasion+/perineural invasion+ was an independent
      prognostic factor for both disease-free survival (hazard ratio = 1.940, 95%
      confidence interval 1.157-3.252, P = 0.012) and overall survival (hazard ratio =
      2.973, 95% confidence interval 1.561-5.662, P = 0.001). CONCLUSIONS: The
      concomitant existence of lymphovascular and perineural invasion has a significant
      prognostic impact on disease-free survival and overall survival in patients with
      Stage II or III gastric cancer.

PMID- 25759485
TI  - Cervical epidural hematoma in a healthy donor presenting stroke mimic symptoms: a
      rare adverse event following peripheral blood stem cell apheresis.
AB  - Peripheral blood stem cell apheresis from a healthy donor is indispensable for
      allogeneic peripheral blood stem cell transplantation. Here, we report a rare
      adverse event following peripheral blood stem cell apheresis. A female sibling
      donor, aged 61 years with an unremarkable medical history, complained of pain in
      the left neck and shoulder and numbness in the left upper limb 1 h after the end
      of peripheral blood stem cell apheresis. Paralysis of the left upper and lower
      limbs appeared consecutively. Computed tomography and magnetic resonance imaging
      of the head showed no abnormalities. Anticoagulant therapy was initiated
      according to the standard treatment of atherothrombotic brain infarction.
      Magnetic resonance imaging of the cervical cord on the following day revealed a
      cervical epidural hematoma. An emergency C4-C5 laminectomy was performed, and the
      paralysis was improved immediately after surgery. This report is the first case
      of cervical epidural hematoma in a healthy donor who underwent peripheral blood
      stem cell apheresis and presented symptoms confusingly similar to those of brain
      infarction. 

PMID- 25759486
TI  - Fatal adverse drug reactions of anticancer drugs detected by all-case post
      marketing surveillance in Japan.
AB  - OBJECTIVE: All-case post-marketing surveillance of newly approved anticancer
      drugs is usually conducted on all patients in Japan. The present study
      investigates whether all-case post-marketing surveillance identifies fatal
      adverse drug reactions undetected before market entry. METHODS: We examined fatal
      adverse drug reactions identified via all-case post-marketing surveillance by
      reviewing the disclosed post-marketing surveillance results, and determined the
      time points in which the fatal adverse drug reactions were initially reported by
      reviewing drug labels. We additionally scanned emergency alerts on the Japanese
      regulatory authority website to assess the relationship between all-case post
      marketing surveillance and regulatory action. RESULTS: Twenty-five all-case post
      marketing surveillances were performed between January 1999 and December 2009.
      Eight all-case post-marketing surveillances with final results included
      information on all fatal cases. Of these, the median number of patients was 1287
      (range: 106-4998), the median number of fatal adverse drug reactions was 14.5
      (range: 4-23). Of the 111 fatal adverse drug reactions detected in the eight post
      marketing surveillances, only 28 (25.0%) and 22 (19.6%) were described on the
      initial global and the initial Japanese drug label, respectively, and 58 (52.3%)
      fatal adverse drug reactions were first described in the all-case post-marketing
      surveillance reports. Despite this, the regulatory authority issued only four
      warning letters, and two of these were prompted by case reports from the all-case
      post-marketing surveillance. CONCLUSION: All-case post-marketing surveillance of
      newly approved anticancer drugs in Japan was useful for the rigorous compilation
      of non-specific adverse drug reactions, but it rarely detected clinically
      significant fatal adverse drug reactions.

PMID- 25759487
TI  - Use of a Transition of Care Coordinator to Improve Ambulatory Follow-up After
      Hospital Discharge.

PMID- 25759488
TI  - Retrograde Wiring of Collateral Channels of the Heart in Chronic Total
      Occlusions: A Systematic Review and Meta-Analysis of Safety, Feasibility, and
      Incremental Value in Achieving Revascularization.
AB  - AIM: To conduct a systematic review and meta-analysis on retrograde wiring in
      chronic total occlusions (CTOs) with focus on its safety and feasibility. METHODS
      AND RESULTS: We searched publications from 1990 to December 2013 in PubMed, Ovid,
      EMBASE, and the Cochrane database inserting a number of terms relating to the
      collateral circulation of the heart in CTOs. A total of 18 case series (n range17
      462) with a total of 2280 CTO revascularization attempts fulfilled criteria for a
      study of retrograde wiring of collateral channels in CTOs. There were no
      randomized studies comparing a primary antegrade with a primary retrograde
      approach. Procedural CTO revascularization rates ranged from 67% to 90.6% with a
      large proportion having previously failed an "antegrade" approach. The septal
      perforator collaterals and epicardial channels were used in 73.2% (n = 1670) and
      21.7% (n = 495) of cases. Although collateral/coronary perforation was not
      infrequent (n = 90, 5%), serious acute complications were uncommon; in the
      combined population 18 cases of cardiac tamponade (0.8%) and 3 deaths (0.1%).
      Septal perforating wiring (79.3%) was significantly more likely to be successful
      compared to epicardial coronary artery wiring (72.5%) when chosen by the operator
      as a route of retrograde access to the CTO body (relative risk 1.11 [95%
      confidence interval: 1.02-1.20; P = .013]). CONCLUSION: Successful retrograde
      wiring of collateral channels in selected patients undertaken by "CTO dedicated"
      operators can significantly enhance the chances of revascularization of complex
      CTOs with a low risk of acute serious complications. Septal perforator channels
      are significantly more likely to be successfully retrogradely wired compared to
      epicardial vessels when either is selected, by reference to their anatomical
      suitability by the operator, as a route of access.

PMID- 25759489
TI  - The aftermath of the Bougainville Crisis: Mental health and psychosocial impacts
      and the need for services.

PMID- 25759490
TI  - Un-rapping teen spirit: Use of rap music as a treatment tool in adolescence
      psychiatry.

PMID- 25759491
TI  - Expert leadership: Doctors versus managers for the executive leadership of
      Australian mental health.

PMID- 25759492
TI  - Correction for Noack et al., How viruses Hijack the ERAD tuning machinery.

PMID- 25759493
TI  - Correction for Hao et al., Infection and propagation of human rhinovirus C in
      human airway epithelial cells.

PMID- 25759495
TI  - Perinatal outcomes in a subsequent pregnancy among women who have experienced
      recurrent miscarriage: a retrospective cohort study.
AB  - STUDY QUESTION: Is a history of three or more miscarriages associated with
      adverse perinatal outcomes in a subsequent pregnancy? SUMMARY ANSWER: Recurrent
      miscarriage is associated with an increased risk of adverse perinatal outcomes,
      including preterm birth, very preterm birth and perinatal death, in a subsequent
      pregnancy. WHAT IS KNOWN ALREADY: Published data are conflicting with some
      studies reporting an increase in adverse perinatal outcomes in association with
      prior recurrent miscarriage while others report little or no increase. Large
      scale population-based studies have been lacking. STUDY DESIGN, SIZE, DURATION:
      We performed a retrospective cohort study of 30 053 women with a singleton
      pregnancy who booked for antenatal care and delivery between January 2008 and
      July 2011. PARTICIPANTS/MATERIALS, SETTING, METHODS: All women who attended a
      university affiliated hospital in Ireland had a detailed obstetric history taken,
      recording the outcome of all previous pregnancies. We compared the obstetric and
      perinatal outcomes of 2030 women (6.8%) who had a history of three or more
      miscarriages (recurrent miscarriage) with the outcomes of 28 023 women (93.2%)
      who did not. Logistic regression analyses were performed, adjusting for potential
      confounding factors. MAIN RESULTS AND THE ROLE OF CHANCE: Women with a history of
      recurrent miscarriage were more likely to be obese, to have undergone assisted
      conception, to have had a previous perinatal death, and to be delivered by
      scheduled Caesarean section. Recurrent miscarriage was associated with an
      increased incidence of preterm birth (<37 weeks gestation, 8.1 versus 5.5%, adjOR
      1.54; 95% CI 1.29-1.84), very preterm birth (<32 weeks gestation, 2.2 versus
      1.2%, adjOR 1.80; 95% CI 1.28-2.53), and perinatal death (1.2 versus 0.5%, adjOR
      2.66; 95% CI 1.70-4.14). The results were similar for both primary and secondary
      recurrent miscarriage. LIMITATIONS, REASONS FOR CAUTION: This is a retrospective
      cohort study and while regression analyses adjusted for potential confounding
      factors, residual confounding may persist. The strict definition of recurrent
      miscarriage is three consecutive miscarriages and while each woman in the study
      group had three or more miscarriages, they were only confirmed to be consecutive
      in the primary RM group. The affected women have not been categorized according
      to aetiology of recurrent miscarriage and it may be that adverse outcomes differ
      according to aetiological subgroup. WIDER IMPLICATIONS OF THE FINDINGS: This
      study highlights the need for specialist obstetric care for women who have had
      three or more previous miscarriages, particularly in relation to the risk of
      preterm delivery. STUDY FUNDING/COMPETING INTERESTS: There was no specific
      funding obtained for this study and there are no conflict of interests.

PMID- 25759496
TI  - Bacterial secretions of nonpathogenic Escherichia coli elicit inflammatory
      pathways: a closer investigation of interkingdom signaling.
AB  - There have been many studies on the relationship between nonpathogenic bacteria
      and human epithelial cells; however, the bidirectional effects of the secretomes
      (secreted substances in which there is no direct bacterium-cell contact) have yet
      to be fully investigated. In this study, we use a transwell model to explore the
      transcriptomic effects of bacterial secretions from two different nonpathogenic
      Escherichia coli strains on the human colonic cell line HCT-8 using next
      generation transcriptome sequencing (RNA-Seq). E. coli BL21 and W3110, while
      genetically very similar (99.1% homology), exhibit key phenotypic differences,
      including differences in their production of macromolecular structures (e.g.,
      flagella and lipopolysaccharide) and in their secretion of metabolic byproducts
      (e.g., acetate) and signaling molecules (e.g., quorum-sensing autoinducer 2 [AI
      2]). After analysis of differential epithelial responses to the respective
      secretomes, this study shows for the first time that a nonpathogenic bacterial
      secretome activates the NF-kappaB-mediated cytokine-cytokine receptor pathways
      while also upregulating negative-feedback components, including the NOD-like
      signaling pathway. Because of AI-2's relevance as a bacterium-bacterium signaling
      molecule and the differences in its secretion rates between these strains, we
      investigated its role in HCT-8 cells. We found that the expression of the
      inflammatory cytokine interleukin 8 (IL-8) responded to AI-2 with a pattern of
      rapid upregulation before subsequent downregulation after 24 h. Collectively,
      these data demonstrate that secreted products from nonpathogenic bacteria
      stimulate the transcription of immune-related biological pathways, followed by
      the upregulation of negative-feedback elements that may serve to temper the
      inflammatory response. IMPORTANCE: The symbiotic relationship between the
      microbiome and the host is important in the maintenance of human health. There is
      a growing need to further understand the nature of these relationships to aid in
      the development of homeostatic probiotics and also in the design of novel
      antimicrobial therapeutics. To our knowledge, this is the first global
      transcriptome study of bacteria cocultured with human epithelial cells in a model
      to determine the transcriptional effects of epithelial cells in which epithelial
      and bacterial cells are allowed to "communicate" with each other only through
      diffusible small molecules and proteins. By beginning to demarcate the direct and
      indirect effects of bacteria on the gastrointestinal (GI) tract, two-way
      interkingdom communication can potentially be mediated between host and microbe.

PMID- 25759497
TI  - Transmission and microevolution of USA300 MRSA in U.S. households: evidence from
      whole-genome sequencing.
AB  - Methicillin-resistant Staphylococcus aureus (MRSA) USA300 is a successful S.
      aureus clone in the United States and a common cause of skin and soft tissue
      infections (SSTIs). We performed whole-genome sequencing (WGS) of 146 USA300 MRSA
      isolates from SSTIs and colonization cultures obtained from an investigation
      conducted from 2008 to 2010 in Chicago and Los Angeles households that included
      an index case with an S. aureus SSTI. Identifying unique single nucleotide
      polymorphisms (SNPs) and analyzing whole-genome phylogeny, we characterized
      isolates to understand transmission dynamics, genetic relatedness, and
      microevolution of USA300 MRSA within the households. We also compared the 146
      USA300 MRSA isolates from our study with the previously published genome
      sequences of the USA300 MRSA isolates from San Diego (n = 35) and New York City
      (n = 277). We found little genetic variation within the USA300 MRSA household
      isolates from Los Angeles (mean number of SNPs +/- standard deviation, 17.6 +/-
      35; pi nucleotide diversity, 3.1 * 10(-5)) or from Chicago (mean number of SNPs
      +/- standard deviation, 12 +/- 19; pi nucleotide diversity, 3.1 * 10(-5)). The
      isolates within a household clustered into closely related monophyletic groups,
      suggesting the introduction into and transmission within each household of a
      single common USA300 ancestral strain. From a Bayesian evolutionary
      reconstruction, we inferred that USA300 persisted within households for 2.33 to
      8.35 years prior to sampling. We also noted that fluoroquinolone-resistant USA300
      clones emerged around 1995 and were more widespread in Los Angeles and New York
      City than in Chicago. Our findings strongly suggest that unique USA300 MRSA
      isolates are transmitted within households that contain an individual with an
      SSTI. Decolonization of household members may be a critical component of
      prevention programs to control USA300 MRSA spread in the United States.
      IMPORTANCE: USA300, a virulent and easily transmissible strain of methicillin
      resistant Staphylococcus aureus (MRSA), is the predominant community-associated
      MRSA clone in the United States. It most commonly causes skin infections but also
      causes necrotizing pneumonia and endocarditis. Strategies to limit the spread of
      MRSA in the community can only be effective if we understand the most common
      sources of transmission and the microevolutionary processes that provide a
      fitness advantage to MRSA. We performed a whole-genome sequence comparison of 146
      USA300 MRSA isolates from Chicago and Los Angeles. We show that households
      represent a frequent site of transmission and a long-term reservoir of USA300
      strains; individuals within households transmit the same USA300 strain among
      themselves. Our study also reveals that a large proportion of the USA300 isolates
      sequenced are resistant to fluoroquinolone antibiotics. The significance of this
      study is that if households serve as long-term reservoirs of USA300, household
      MRSA eradication programs may result in a uniquely effective control method.

PMID- 25759498
TI  - Origin, evolution, and virulence of porcine deltacoronaviruses in the United
      States.
AB  - A novel porcine deltacoronavirus (PdCV) was first discovered in Ohio and Indiana
      in February 2014, rapidly spread to other states in the United States and Canada,
      and caused significant economic loss in the swine industry. The origin and
      virulence of this novel porcine coronavirus are not known. Here, we characterized
      U.S. PdCV isolates and determined their virulence in gnotobiotic and conventional
      piglets. Genome analyses revealed that U.S. PdCV isolates possess unique genetic
      characteristics and share a close relationship with Hong Kong and South Korean
      PdCV strains and coronaviruses (CoVs) of Asian leopard cats and Chinese ferret
      badgers. The PdCV-positive intestinal content (Ohio CVM1) and the cell culture
      adapted PdCV Michigan (MI) strain were orally inoculated into gnotobiotic and/or
      conventional piglets. Within 1 to 3 days postinfection, profuse watery diarrhea,
      vomiting, and dehydration were observed. Clinical signs were associated with
      epithelial necrosis in the gastric pits and small intestine, the latter resulting
      in severe villous atrophy. Mild interstitial pneumonia was identified in the
      lungs of PdCV-infected piglets. High levels of viral RNA (8 to 11 log RNA
      copies/g) were detected in intestinal tissues/luminal contents and feces of
      infected piglets, whereas moderate RNA levels (2 to 5 log RNA copies/g) were
      detected in blood, lung, liver, and kidney, indicating multisystemic
      dissemination of the virus. Polyclonal immune serum against PdCV but not immune
      serum against porcine epidemic diarrhea virus (PEDV) reacted with PdCV-infected
      small-intestinal epithelial cells, indicating that PdCV is antigenically distinct
      from PEDV. Collectively, we demonstrate for the first time that PdCV caused
      severe gastrointestinal diseases in swine. IMPORTANCE: Porcine coronaviruses
      (CoVs) are major viral infectious diseases of swine. Examples of porcine CoVs
      include porcine transmissible gastroenteritis coronavirus (TGEV), porcine
      epidemic diarrhea virus (PEDV), and porcine respiratory coronavirus (PRCV). In
      February 2014, another porcine CoV, porcine deltacoronavirus (PdCV), emerged in
      Ohio and Indiana and subsequently spread rapidly across the United States and
      Canada, causing significant economic losses. Here, we report the detailed genetic
      characterization, phylogeny, and virulence of emergent PdCV strains in the United
      States. We found that PdCV caused severe diarrhea, vomiting, and dehydration in
      gnotobiotic and conventional piglets, signs that were clinically
      indistinguishable from those caused by PEDV and TGEV. In addition to extensive
      intestinal lesions, PdCV caused significant lesions in the stomach and mild
      pulmonary lesions that have not been reported for TGEV and PEDV. The finding that
      PdCV is a significant enteric disease of swine highlights the need to develop
      effective measures to control this disease.

PMID- 25759499
TI  - Secretome analysis of Vibrio cholerae type VI secretion system reveals a new
      effector-immunity pair.
AB  - The type VI secretion system (T6SS) is a dynamic macromolecular organelle that
      many Gram-negative bacteria use to inhibit or kill other prokaryotic or
      eukaryotic cells. The toxic effectors of T6SS are delivered to the prey cells in
      a contact-dependent manner. In Vibrio cholerae, the etiologic agent of cholera,
      T6SS is active during intestinal infection. Here, we describe the use of
      comparative proteomics coupled with bioinformatics to identify a new T6SS
      effector-immunity pair. This analysis was able to identify all previously
      identified secreted substrates of T6SS except PAAR (proline, alanine, alanine,
      arginine) motif-containing proteins. Additionally, this approach led to the
      identification of a new secreted protein encoded by VCA0285 (TseH) that carries a
      predicted hydrolase domain. We confirmed that TseH is toxic when expressed in the
      periplasm of Escherichia coli and V. cholerae cells. The toxicity observed in V.
      cholerae was suppressed by coexpression of the protein encoded by VCA0286 (TsiH),
      indicating that this protein is the cognate immunity protein of TseH.
      Furthermore, exogenous addition of purified recombinant TseH to permeabilized E.
      coli cells caused cell lysis. Bioinformatics analysis of the TseH protein
      sequence suggest that it is a member of a new family of cell wall-degrading
      enzymes that include proteins belonging to the YD repeat and Rhs superfamilies
      and that orthologs of TseH are likely expressed by species belonging to phyla as
      diverse as Bacteroidetes and Proteobacteria. IMPORTANCE: The Gram-negative
      bacterium Vibrio cholerae causes cholera, a severe and often lethal diarrheal
      disease. The 2010-2012 epidemic in Haiti and new explosive epidemics in Africa
      show that cholera remains a significant global public health problem. The type VI
      secretion system (T6SS) is a dynamic organelle expressed by many Gram-negative
      bacteria, which use it to inject toxic effector proteins into eukaryotic and
      bacterial prey cells. In this study, we applied a comparative proteomics approach
      to the V. cholerae T6SS secretome to identify new substrates of this secretion
      apparatus. We show that the product of the gene VCA0285 is likely a new
      peptidoglycan hydrolase that is secreted by T6SS and that its cognate immunity
      protein is encoded by the gene that is immediately downstream (VCA0286).
      Bioinformatics analysis shows that VCA0285 carries four conserved motifs that
      likely define a large family of hydrolases with antibacterial activity. The
      identification of new antibacterial T6SS effectors provides useful information
      for the development of novel antibiotics and therapeutic agents.

PMID- 25759500
TI  - Identification of a gamma interferon-activated inhibitor of translation-like RNA
      motif at the 3' end of the transmissible gastroenteritis coronavirus genome
      modulating innate immune response.
AB  - A 32-nucleotide (nt) RNA motif located at the 3' end of the transmissible
      gastroenteritis coronavirus (TGEV) genome was found to specifically interact with
      the host proteins glutamyl-prolyl-tRNA synthetase (EPRS) and arginyl-tRNA
      synthetase (RRS). This RNA motif has high homology in sequence and secondary
      structure with the gamma interferon-activated inhibitor of translation (GAIT)
      element, which is located at the 3' end of several mRNAs encoding proinflammatory
      proteins. The GAIT element is involved in the translation silencing of these
      mRNAs through its interaction with the GAIT complex (EPRS, heterogeneous nuclear
      ribonucleoprotein Q, ribosomal protein L13a, and glyceraldehyde 3-phosphate
      dehydrogenase) to favor the resolution of inflammation. Interestingly, we showed
      that the viral RNA motif bound the GAIT complex and inhibited the in vitro
      translation of a chimeric mRNA containing this RNA motif. To our knowledge, this
      is the first GAIT-like motif described in a positive RNA virus. To test the
      functional role of the GAIT-like RNA motif during TGEV infection, a recombinant
      coronavirus harboring mutations in this motif was engineered and characterized.
      Mutations of the GAIT-like RNA motif did not affect virus growth in cell
      cultures. However, an exacerbated innate immune response, mediated by the
      melanoma differentiation-associated gene 5 (MDA5) pathway, was observed in cells
      infected with the mutant virus compared with the response observed in cells
      infected with the parental virus. Furthermore, the mutant virus was more
      sensitive to beta interferon than the parental virus. All together, these data
      strongly suggested that the viral GAIT-like RNA motif modulates the host innate
      immune response. IMPORTANCE: The innate immune response is the first line of
      antiviral defense that culminates with the synthesis of interferon and
      proinflammatory cytokines to limit virus replication. Coronaviruses encode
      several proteins that interfere with the innate immune response at different
      levels, but to date, no viral RNA counteracting antiviral response has been
      described. In this work, we have characterized a 32-nt RNA motif located at the
      3' end of the TGEV genome that specifically interacted with EPRS and RRS. This
      RNA motif presented high homology with the GAIT element, involved in the
      modulation of the inflammatory response. Moreover, the disruption of the viral
      GAIT-like RNA motif led to an exacerbated innate immune response triggered by
      MDA5, indicating that the GAIT-like RNA motif counteracts the host innate immune
      response. These novel findings may be of relevance for other coronaviruses and
      could serve as the basis for the development of novel antiviral strategies.

PMID- 25759501
TI  - Regulation of Plasmodium yoelii oocyst development by strain- and stage-specific
      small-subunit rRNA.
AB  - One unique feature of malaria parasites is the differential transcription of
      structurally distinct rRNA (rRNA) genes at different developmental stages: the A
      type genes are transcribed mainly in asexual stages, whereas the S-type genes are
      expressed mostly in sexual or mosquito stages. Conclusive functional evidence of
      different rRNAs in regulating stage-specific parasite development, however, is
      still absent. Here we performed genetic crosses of Plasmodium yoelii parasites
      with one parent having an oocyst development defect (ODD) phenotype and another
      producing normal oocysts to identify the gene(s) contributing to the ODD. The
      parent with ODD--characterized as having small oocysts and lacking infective
      sporozoites--was obtained after introduction of a plasmid with a green
      fluorescent protein gene into the parasite genome and subsequent passages in
      mice. Quantitative trait locus analysis of genome-wide microsatellite genotypes
      of 48 progeny from the crosses linked an ~200-kb segment on chromosome 6
      containing one of the S-type genes (D-type small subunit rRNA gene [D-ssu]) to
      the ODD. Fine mapping of the plasmid integration site, gene expression pattern,
      and gene knockout experiments demonstrated that disruption of the D-ssu gene
      caused the ODD phenotype. Interestingly, introduction of the D-ssu gene into the
      same parasite strain (self), but not into a different subspecies, significantly
      affected or completely ablated oocyst development, suggesting a stage- and
      subspecies (strain)-specific regulation of oocyst development by D-ssu. This
      study demonstrates that P. yoelii D-ssu is essential for normal oocyst and
      sporozoite development and that variation in the D-ssu sequence can have dramatic
      effects on parasite development. IMPORTANCE: Malaria parasites are the only known
      organisms that express structurally distinct rRNA genes at different
      developmental stages. The differential expression of these genes suggests that
      they play unique roles during the complex life cycle of the parasites. Conclusive
      functional proof of different rRNAs in regulating parasite development, however,
      is still absent or controversial. Here we functionally demonstrate for the first
      time that a stage-specifically expressed D-type small-subunit rRNA gene (D-ssu)
      is essential for oocyst development of the malaria parasite Plasmodium yoelii in
      the mosquito. This study also shows that variations in D-ssu sequence and/or the
      timing of transcription may have profound effects on parasite oocyst development.
      The results show that in addition to protein translation, rRNAs of malaria
      parasites also regulate parasite development and differentiation in a strain
      specific manner, which can be explored for controlling parasite transmission.

PMID- 25759502
TI  - A group A Streptococcus ADP-ribosyltransferase toxin stimulates a protective
      interleukin 1beta-dependent macrophage immune response.
AB  - The M1T1 clone of group A Streptococcus (GAS) is associated with severe invasive
      infections, including necrotizing fasciitis and septicemia. During invasive M1T1
      GAS disease, mutations in the covRS regulatory system led to upregulation of an
      ADP-ribosyltransferase, SpyA. Surprisingly, a GAS DeltaspyA mutant was resistant
      to killing by macrophages and caused higher mortality with impaired bacterial
      clearance in a mouse intravenous challenge model. GAS expression of SpyA
      triggered macrophage cell death in association with caspase-1-dependent
      interleukin 1beta (IL-1beta) production, and differences between wild-type (WT)
      and DeltaspyA GAS macrophage survival levels were lost in cells lacking caspase
      1, NOD-like receptor protein 3 (NLRP3), apoptosis-associated speck-like protein
      (ASC), or pro-IL-1beta. Similar in vitro findings were identified in macrophage
      studies performed with pseudomonal exotoxin A, another ADP-ribosylating toxin.
      Thus, SpyA triggers caspase-1-dependent inflammatory cell death in macrophages,
      revealing a toxin-triggered IL-1beta-dependent innate immune response pathway
      critical in defense against invasive bacterial infection. IMPORTANCE: Group A
      Streptococcus (GAS) is a leading human pathogen capable of producing invasive
      infections even in healthy individuals. GAS bacteria produce a toxin called SpyA
      that modifies host proteins through a process called ADP ribosylation. We
      describe how macrophages, frontline defenders of the host innate immune system,
      respond to SpyA by undergoing a specialized form of cell death in which they are
      activated to release the proinflammatory cytokine molecule interleukin 1beta (IL
      1beta). Release of IL-1beta activates host immune cell clearance of GAS, as we
      demonstrated in tissue culture models of macrophage bacterial killing and in vivo
      mouse infectious-challenge experiments. Similar macrophage responses to a related
      toxin of Pseudomonas bacteria were also shown. Thus, macrophages recognize
      certain bacterial toxins to activate a protective immune response in the host.

PMID- 25759503
TI  - The importance of virology at a time of great need and great jeopardy.

PMID- 25759504
TI  - New method for the orthogonal labeling and purification of Toxoplasma gondii
      proteins while inside the host cell.
AB  - Toxoplasma gondii is an obligate intracellular protozoan parasite that is capable
      of causing severe disease in immunocompromised humans. How T. gondii is able to
      modulate the host cell to support itself is still poorly understood. Knowledge
      pertaining to the host-parasite interaction could be bolstered by developing a
      system to specifically label parasite proteins while the parasite grows inside
      the host cell. For this purpose, we have created a strain of T. gondii that
      expresses a mutant Escherichia coli methionyl-tRNA synthetase (MetRS(NLL)) that
      allows methionine tRNA to be loaded with the azide-containing methionine analog
      azidonorleucine (Anl). Anl-containing proteins are susceptible to a copper
      catalyzed "click" reaction to attach affinity tags for purification or
      fluorescent tags for visualization. The MetRS(NLL)-Anl system labels nascent T.
      gondii proteins in an orthogonal fashion, labeling proteins only in MetRS(NLL)
      expressing parasites. This system should be useful for nonradioactive pulse-chase
      studies and purification of nascently translated proteins. Although this approach
      allows labeling of a diverse array of parasite proteins, secreted parasite
      proteins appear to be only minimally labeled in MetRS(NLL)-expressing T. gondii.
      The minimal labeling of secreted proteins is likely a consequence of the
      selective charging of the initiator tRNA (and not the elongator methionine tRNA)
      by the heterologously expressed bacterial MetRS. IMPORTANCE: Studying how T.
      gondii modifies the host cell to permit its survival is complicated by the
      complex protein environment of the host cell. The approach presented in this
      article provides the first method for specific labeling of T. gondii proteins
      while the parasite grows inside the host cell. We show that this approach is
      useful for pulse-chase labeling of parasite proteins during in vitro growth. It
      should also be applicable during in vivo infections and in other apicomplexan
      parasites, including Plasmodium spp.

PMID- 25759505
TI  - Heparan sulfate-dependent enhancement of henipavirus infection.
AB  - Nipah virus and Hendra virus are emerging, highly pathogenic, zoonotic
      paramyxoviruses that belong to the genus Henipavirus. They infect humans as well
      as numerous mammalian species. Both viruses use ephrin-B2 and -B3 as cell entry
      receptors, and following initial entry into an organism, they are capable of
      rapid spread throughout the host. We have previously reported that Nipah virus
      can use another attachment receptor, different from its entry receptors, to bind
      to nonpermissive circulating leukocytes, thereby promoting viral dissemination
      within the host. Here, this attachment molecule was identified as heparan sulfate
      for both Nipah virus and Hendra virus. Cells devoid of heparan sulfate were not
      able to mediate henipavirus trans-infection and showed reduced permissivity to
      infection. Virus pseudotyped with Nipah virus glycoproteins bound heparan sulfate
      and heparin but no other glycosaminoglycans in a surface plasmon resonance assay.
      Furthermore, heparin was able to inhibit the interaction of the viruses with the
      heparan sulfate and to block cell-mediated trans-infection of henipaviruses.
      Moreover, heparin was shown to bind to ephrin-B3 and to restrain infection of
      permissive cells in vitro. Consequently, treatment with heparin devoid of
      anticoagulant activity improved the survival of Nipah virus-infected hamsters.
      Altogether, these results reveal heparan sulfate as a new attachment receptor for
      henipaviruses and as a potential therapeutic target for the development of novel
      approaches against these highly lethal infections. IMPORTANCE: The Henipavirus
      genus includes two closely related, highly pathogenic paramyxoviruses, Nipah
      virus and Hendra virus, which cause elevated morbidity and mortality in animals
      and humans. Pathogenesis of both Nipah virus and Hendra virus infection is poorly
      understood, and efficient antiviral treatment is still missing. Here, we
      identified heparan sulfate as a novel attachment receptor used by both viruses to
      bind host cells. We demonstrate that heparin was able to inhibit the interaction
      of the viruses with heparan sulfate and to block cell-mediated trans-infection of
      henipaviruses. Moreover, heparin also bound to the viral entry receptor and
      thereby restricted infection of permissive cells in vitro. Consequently, heparin
      treatment improved survival of Nipah virus-infected hamsters. These results
      uncover an important role of heparan sulfate in henipavirus infection and open
      novel perspectives for the development of heparan sulfate-targeting therapeutic
      approaches for these emerging infections.

PMID- 25759506
TI  - Vaccination with adjuvanted recombinant neuraminidase induces broad heterologous,
      but not heterosubtypic, cross-protection against influenza virus infection in
      mice.
AB  - In an attempt to assess the cross-protective potential of the influenza virus
      neuraminidase (NA) as a vaccine antigen, different subtypes of recombinant NA
      were expressed in a baculovirus system and used to vaccinate mice prior to lethal
      challenge with homologous, heterologous, or heterosubtypic viruses. Mice
      immunized with NA of subtype N2 were completely protected from morbidity and
      mortality in a homologous challenge and displayed significantly reduced viral
      lung titers. Heterologous challenge with a drifted strain resulted in morbidity
      but no mortality. Similar results were obtained for challenge experiments with N1
      NA. Mice immunized with influenza B virus NA (from B/Yamagata/16/88) displayed no
      morbidity when sublethally infected with the homologous strain and, importantly,
      were completely protected from morbidity and mortality when lethally challenged
      with the prototype Victoria lineage strain or a more recent Victoria lineage
      isolate. Upon analyzing the NA content in 4 different inactivated-virus vaccine
      formulations from the 2013-2014 season via Western blot assay and enzyme-linked
      immunosorbent assay quantification, we found that the amount of NA does indeed
      vary across vaccine brands. We also measured hemagglutinin (HA) and NA endpoint
      titers in pre- and postvaccination human serum samples from individuals who
      received a trivalent inactivated seasonal influenza vaccine from the 2004-2005
      season; the induction of NA titers was statistically less pronounced than the
      induction of HA titers. The demonstrated homologous and heterologous protective
      capacity of recombinant NA suggests that supplementing vaccine formulations with
      a standard amount of NA may offer increased protection against influenza virus
      infection. IMPORTANCE: Despite the existence of vaccine prophylaxis and antiviral
      therapeutics, the influenza virus continues to cause morbidity and mortality in
      the human population, emphasizing the continued need for research in the field.
      While the majority of influenza vaccine strategies target the viral
      hemagglutinin, the immunodominant antigen on the surface of the influenza virion,
      antibodies against the viral neuraminidase (NA) have been correlated with less
      severe disease and decreased viral shedding in humans. Nevertheless, the amount
      of NA is not standardized in current seasonal vaccines, and the exact breadth of
      NA-based protection is unknown. Greater insight into the cross-protective
      potential of influenza virus NA as a vaccine antigen may pave the way for the
      development of influenza vaccines of greater breadth and efficacy.

PMID- 25759508
TI  - Hinge-Region O-Glycosylation of Human Immunoglobulin G3 (IgG3).
AB  - Immunoglobulin G (IgG) is one of the most abundant proteins present in human
      serum and a fundamental component of the immune system. IgG3 represents ~8% of
      the total amount of IgG in human serum and stands out from the other IgG
      subclasses because of its elongated hinge region and enhanced effector functions.
      This study reports partial O-glycosylation of the IgG3 hinge region, observed
      with nanoLC-ESI-IT-MS(/MS) analysis after proteolytic digestion. The repeat
      regions within the IgG3 hinge were found to be in part O-glycosylated at the
      threonine in the triple repeat motif. Non-, mono- and disialylated core 1-type O
      glycans were detected in various IgG3 samples, both poly- and monoclonal. NanoLC
      ESI-IT-MS/MS with electron transfer dissociation fragmentation and CE-MS/MS with
      CID fragmentation were used to determine the site of IgG3 O-glycosylation. The O
      glycosylation site was further confirmed by the recombinant production of mutant
      IgG3 in which potential O-glycosylation sites had been knocked out. For IgG3
      samples from six donors we found similar O-glycan structures and site
      occupancies, whereas for the same samples the conserved N-glycosylation of the Fc
      CH2 domain showed considerable interindividual variation. The occupancy of each
      of the three O-glycosylation sites was found to be ~10% in six serum-derived IgG3
      samples and ~13% in two monoclonal IgG3 allotypes. 

PMID- 25759510
TI  - Real-time detection of lipid bilayer assembly and detergent-initiated
      solubilization using optical cavities.
AB  - The cellular membrane governs numerous fundamental biological processes.
      Therefore, developing a comprehensive understanding of its structure and function
      is critical. However, its inherent biological complexity gives rise to numerous
      inter-dependent physical phenomena. In an attempt to develop a model, two
      different experimental approaches are being pursued in parallel: performing
      single cell experiments (top down) and using biomimetic structures (bottom up),
      such as lipid bilayers. One challenge in many of these experiments is the
      reliance on fluorescent probes for detection which can create confounds in this
      already complex system. In the present work, a label-free detection method based
      on an optical resonant cavity is used to detect one of the fundamental physical
      phenomena in the system: assembly and solubilization of the lipid bilayer. The
      evanescent field of the cavity strongly interacts with the lipid bilayer,
      enabling the detection of the bilayer behavior in real-time. Two independent
      detection mechanisms confirm the formation and detergent-assisted solubilization
      of the lipid bilayers: (1) a refractive index change and (2) a material loss
      change. Both mechanisms can be monitored in parallel, on the same device, thus
      allowing for cross-confirmation of the results. To verify the proposed method, we
      have detected the formation of self-assembled phosphatidylcholine lipid bilayers
      from small unilamellar vesicles on the device surface in real-time. Subsequently,
      we exposed the bilayers to two different detergents (non-ionic Triton X-100 and
      anionic sodium dodecyl sulfate) to initiate solubilization, and this process was
      also detected in real-time. After the bilayer solubilization, the device returned
      to its initial state, exhibiting minimal hysteresis. The experimental wash-off
      was also collected and analyzed using dynamic light scattering.

PMID- 25759509
TI  - A Fluorescent Live Imaging Screening Assay Based on Translocation Criteria
      Identifies Novel Cytoplasmic Proteins Implicated in G Protein-coupled Receptor
      Signaling Pathways.
AB  - Several cytoplasmic proteins that are involved in G protein-coupled receptor
      signaling cascades are known to translocate to the plasma membrane upon receptor
      activation, such as beta-arrestin2. Based on this example and in order to
      identify new cytoplasmic proteins implicated in the ON-and-OFF cycle of G protein
      coupled receptor, a live-imaging screen of fluorescently labeled cytoplasmic
      proteins was performed using translocation criteria. The screening of 193
      fluorescently tagged human proteins identified eight proteins that responded to
      activation of the tachykinin NK2 receptor by a change in their intracellular
      localization. Previously we have presented the functional characterization of one
      of these proteins, REDD1, that translocates to the plasma membrane. Here we
      report the results of the entire screening. The process of cell activation was
      recorded on videos at different time points and all the videos can be visualized
      on a dedicated website. The proteins BAIAP3 and BIN1, partially translocated to
      the plasma membrane upon activation of NK2 receptors. Proteins ARHGAP12 and PKM2
      translocated toward membrane blebs. Three proteins that associate with the
      cytoskeleton were of particular interest : PLEKHH2 rearranged from individual
      dots located near the cell-substrate adhesion surface into lines of dots. The
      speriolin-like protein, SPATC1L, redistributed to cell-cell junctions. The
      Chloride intracellular Channel protein, CLIC2, translocated from actin-enriched
      plasma membrane bundles to cell-cell junctions upon activation of NK2 receptors.
      CLIC2, and one of its close paralogs, CLIC4, were further shown to respond with
      the same translocation pattern to muscarinic M3 and lysophosphatidic LPA
      receptors. This screen allowed us to identify potential actors in signaling
      pathways downstream of G protein-coupled receptors and could be scaled-up for
      high-content screening. 

PMID- 25759511
TI  - Analysis of the surface density and reactivity of perfluorophenylazide and the
      impact on ligand immobilization.
AB  - Perfluorophenylazide (PFPA) chemistry is a novel method for tailoring the surface
      properties of solid surfaces and nanoparticles. It is general and versatile, and
      has proven to be an efficient way to immobilize graphene, proteins,
      carbohydrates, and synthetic polymers. The main thrust of this work is to provide
      a detailed investigation on the chemical composition and surface density of the
      PFPA tailored surface. Specifically, gold surfaces were treated with PFPA
      derivatized (11-mercaptoundecyl)tetra(ethylene glycol) (PFPA-MUTEG) mixed with 2
      [2-(2-mercaptoethoxy)ethoxy]ethanol (MDEG) at varying solution mole ratios.
      Complementary analytical techniques were employed to characterize the resulting
      films including Fourier transform infrared spectroscopy to detect fingerprints of
      the PFPA group, x-ray photoelectron spectroscopy and ellipsometry to study the
      homogeneity and uniformity of the films, and near edge x-ray absorption fine
      structures to study the electronic and chemical structure of the PFPA groups.
      Results from these studies show that the films prepared from 90:10 and 80:20 PFPA
      MUTEG/MDEG mixed solutions exhibited the highest surface density of PFPA and the
      most homogeneous coverage on the surface. A functional assay using surface
      plasmon resonance with carbohydrates covalently immobilized onto the PFPA
      modified surfaces showed the highest binding affinity for lectin on the PFPA
      MUTEG/MDEG film prepared from a 90:10 solution.

PMID- 25759512
TI  - Proton pump inhibitor alone vs proton pump inhibitor plus mucosal protective
      agents for endoscopic submucosal dissection-induced ulcer: a systematic review
      and meta-analysis.
AB  - Mucosal protective agents may improve healing of patients with endoscopic
      submucosal dissection-induced ulcers. The present study systematically evaluated
      published clinical trials to determine whether combined therapeutic use of
      mucosal protective agents and proton pump inhibitors can improve the outcome of
      patients with endoscopic submucosal dissection-induced ulcers compared to
      treatment with proton pump inhibitors alone. PubMed, the Cochrane Library, and
      the Igaku-Chuo-Zasshi database were searched to identify eligible randomized
      trials for systematic review. We identified 11 randomized trials for inclusion in
      our study (1,160 patients). Pooled endoscopic submucosal dissection-induced ulcer
      healing rates were 45.8% and 34.4% for patients with or without mucosal
      protective agents, respectively. The odds ratio was 2.28 (95% confidence
      interval, 1.57-3.31) with no significant study heterogeneity. In conclusion, the
      systematic review and meta-analysis showed that the combined therapeutic use of
      proton pump inhibitors and mucosal protective agents improved healing rates of
      endoscopic submucosal dissection-induced ulcers compared to treatment with proton
      pump inhibitor monotherapy. 

PMID- 25759513
TI  - Emerging functional cross-talk between the Keap1-Nrf2 system and mitochondria.
AB  - Nuclear factor erythroid-derived 2-related factor 2 (Nrf2) was originally
      identified as a positive regulator of drug detoxifying enzyme gene expression
      during exposure to environmental electrophiles. Currently, Nrf2 is known to
      regulate the expression of hundreds of cytoprotective genes to counteract
      endogenously or exogenously generated oxidative stress. Furthermore, when
      activated in human tumors by somatic mutations, Nrf2 confers growth advantages
      and chemoresistance by regulating genes involved in various processes such as the
      pentose phosphate pathway and nucleotide synthesis in addition to antioxidant
      proteins. Interestingly, increasing evidence shows that Nrf2 is associated with
      mitochondrial biogenesis during environmental stresses in certain tissues such as
      the heart. Furthermore, SKN-1, a functional homolog of Nrf2 in C. elegans, is
      activated by mitochondrial reactive oxygen species and extends life span by
      promoting mitochondrial homeostasis (i.e., mitohormesis). Similarly, Nrf2
      activation was recently observed in the heart of surfeit locus protein 1 (Surf1) 
      /- mice in which cellular respiration was decreased due to cytochrome c oxidase
      defects. In this review, we critically examine the relationship between Nrf2 and
      mitochondria and argue that the Nrf2 stress pathway intimately communicates with
      mitochondria to maintain cellular homeostasis during oxidative stress. 

PMID- 25759514
TI  - Contribution of nitrergic nerve in canine gingival reactive hyperemia.
AB  - Reactive hyperemia reflects a compensatory vasodilation response of the local
      vasculature in ischemic tissue. The purpose of this study is to clarify the
      mechanism of regulation of this response in gingival circulation by using
      pharmacological analysis of reactive hyperemia and histochemical analysis of
      gingival tissue. Application of pressure to the gingiva was used to create
      temporary ischemia, and gingival blood flow was measured after pressure release.
      Reactive hyperemia increased in proportion to the duration of pressure. Systemic
      hemodynamics remained unaffected by the stimulus; therefore, the gingival
      reactive hyperemia reflected a local adjustment in circulation. Gingival reactive
      hyperemia was significantly suppressed by nitric oxide (NO) synthase inhibitors,
      especially the neural NO synthase-selective antagonist 7-nitroindazole, but not
      by anticholinergic drugs, beta-blockers, or antihistaminergic drugs. Moreover,
      immunohistochemical staining for neural NO synthase and histochemical staining
      for NADPH diaphorase activity were both positive in the gingival perivascular
      region. These histochemical and pharmacological analyses show that reactive
      hyperemia following pressure release is mediated by NO-induced vasodilation.
      Furthermore, histochemical analysis strongly suggests that NO originates from
      nitrergic nerves. Therefore, NO may play an important role in the neural
      regulation of local circulation in gingival tissue ischemia. 

PMID- 25759515
TI  - Novel antioxidant capacity assay for lipophilic compounds using electron
      paramagnetic resonance spectroscopy.
AB  - A novel antioxidant capacity assay for lipophilic compounds was developed using
      electron paramagnetic resonance (EPR) spectroscopy. The assay is based on
      antioxidant's scavenging ability against the tert-butoxyl radical generated
      photolytically from di-tert-butyl peroxide in ethyl acetate, and named the tert
      butoxyl-based antioxidant capacity (BAC) assay. The radical was trapped by spin
      trap, 5,5-dimethyl-1-pyrroline-N-oxide, and EPR signal intensity of the spin
      adduct was used as a quantitative marker of radical levels. Signal intensity
      decreased in a dose-dependent manner in the presence of an antioxidant that
      competitively reacts with the radical, which was utilized to evaluate BAC values.
      The BAC method enabled the accurate estimation of antioxidant capacity for
      lipophilic materials that may counteract lipid peroxidation in biological
      membranes. The BAC values for quercetin and caffeic acid are 0.639 +/- 0.020 and
      0.118 +/- 0.012 trolox equivalents, respectively, which are much smaller than
      values obtained by other aqueous methods such as H-ORAC and ORAC-EPR. Thus,
      antioxidants present in a non-aqueous environment should be evaluated using a non
      aqueous system. In combination with in situ ascorbate reduction, the BAC method
      was capable of accurately determining the antioxidant capacity of water-insoluble
      materials that may be reduced in living cells. 

PMID- 25759516
TI  - Asbestos and multi-walled carbon nanotubes generate distinct oxidative responses
      in inflammatory cells.
AB  - Asbestos exposure is considered a social burden by causing mesothelioma. Despite
      the use of synthetic materials, multi-walled carbon nanotubes (MWCNTs) are
      similar in dimension to asbestos and produce mesothelioma in animals. The role of
      inflammatory cells in mesothelial carcinogenesis remains unclear. Here, we
      evaluated the differences in inflammatory cell responses following exposure to
      these fibrous materials using a luminometer and L-012 (8-amino-5-chloro-7
      phenylpyrido[3,4-d]pyridazine-1,4-(2H,3H) dione) to detect reactive oxygen
      species (ROS). Rat peripheral blood or RAW264.7 cells were used to assess the
      effects on neutrophils and macrophages, respectively. Crocidolite and amosite
      induced significant ROS generation by neutrophils with a peak at 10 min, whereas
      that of chrysotile was ~25% of the crocidolite/amosite response. MWCNTs with
      different diameters (~15, 50, 115 and 145 nm) and different carcinogenicity did
      not induce significant ROS in peripheral blood. However, the MWCNTs induced a
      comparable amount of ROS in RAW264.7 cells to that following asbestos treatment.
      The peaks for MWCNTs (0.5-1.5 h) were observed earlier than those for asbestos (1
      5 h). Apocynin and superoxide dismutase significantly inhibited ROS generation
      for each fiber, suggesting an involvement of NADPH oxidase and superoxide. Thus,
      asbestos and MWCNTs induce different oxidative responses in inflammatory cells,
      indicating the importance of mesothelial cell evaluation for carcinogenesis. 

PMID- 25759517
TI  - Involvement of NADPH oxidases in suppression of cyclooxygenase-2 promoter
      dependent transcriptional activities by sesamol.
AB  - Cyclooxygenase-2 (COX-2) has been shown to play an important role in colon
      carcinogenesis. Moreover, one of the components of reduced nicotinamide adenine
      dinucleotide phosphate (NADPH) oxidase, NADPH oxidase 1 (NOX1), dominantly
      expressed in the colon, is implicated in the pathogenesis of colon cancer. We
      have reported that sesamol, one of the lignans in sesame seeds, suppressed COX-2
      gene transcriptional activity in human colon cancer cells, and also suppressed
      intestinal polyp formation in Apc-mutant mice. In the present study, we
      investigated the involvement of NADPH oxidase in the inhibition of COX-2
      transcriptional activity by sesamol. We found that several NADPH oxidase
      inhibitors, such as apocynin, showed suppressive effects on COX-2 transcriptional
      activity. Moreover, sesamol significantly suppressed NOX1 mRNA levels in a dose
      dependent manner. In addition, we demonstrated that knockdown of NOX1
      successfully suppressed COX-2 transcriptional activity. These results suggest
      that inhibition of NADPH oxidase, especially NOX1, may be involved in the
      mechanism of the suppression of COX-2 transcriptional activity by sesamol. 

PMID- 25759518
TI  - Measurement of lysine-specific demethylase-1 activity in the nuclear extracts by
      flow-injection based time-of-flight mass spectrometry.
AB  - Lysine-specific demethylase 1 (LSD1/KDM1A), a histone-modifying enzyme, is
      upregulated in many cancers, especially in neuroblastoma, breast cancer and
      hepatoma. We have established a simple method to measure LSD1 activity using a
      synthetic N-terminal 21-mer peptide of histone H3, which is dimethylated at Lys-4
      (H3K4me2). After the enzyme reaction, a substrate of H3K4me2 and two demethylated
      products, H3K4me1 and H3K4me0, were quantitatively determined by flow injection
      time-of-flight mass spectrometry (FI-TOF/MS). By using recombinant human LSD1, a
      nonlinear fitting simulation of the data obtained by FI-TOF/MS produced typical
      consecutive-reaction kinetics. Apparent K m and k cat values of hLSD1 for the
      first and second demethylation reactions were found to be in the range of
      reported values. Tranylcypromine was shown to inhibit LSD1 activity with an IC50
      of 6.9 uM for the first demethylation reaction and 5.8 uM for the second
      demethylation reaction. The FI-TOF/MS assay revealed that the endogenous LSD1
      activity was higher in the nuclear extracts of SH-SY5Y cells than in HeLa or PC-3
      cells, and this is in accordance with the immunoblotting data using an anti-LSD1
      antibody. A simple, straightforward FI-TOF/MS assay is described to efficiently
      measure LSD1 activity in the nuclear extracts of cultured cells. 

PMID- 25759519
TI  - Nrf2-mediated mucoprotective and anti-inflammatory actions of Artemisia extracts
      led to attenuate stress related mucosal damages.
AB  - The aim of this study was to compare biological actions between isopropanol and
      ethanol extracts of Artemisia including antioxidant, anti-inflammatory, and
      cytoprotective actions. Antioxidant activities were evaluated using 2,2-diphenyl
      1-picrylhydrazyl (DPPH) method and confocal microscopy on lipopolysaccharide
      induced RGM1 cells, cytoprotection effects evaluated by detecting heme oxygenase
      1 (HO-1), Nf-E2 related factor2 (Nrf2) and heat shock protein 70 (HSP70), and
      anti-inflammatory effects investigated by measuring inflammatory mediators. Water
      immersion restraint stress was imposed to provoke stress related mucosal damages
      (SRMD) in rats. Isopropanol extracts of Artemisia showed the higher DPPH radical
      scavenging activity and lesser LPS-induced reactive oxygen species productions
      and increased HO-1 expression through increased nuclear translocation of Nrf2
      transcription factor compared to ethanol extracts. The increased expression of
      HSP70 and decreased expression of endothelin-1 were only increased with
      isopropanol extracts. A concentration-dependent inhibition of LPS-induced COX-2
      and iNOS even at a rather lower concentration than ethanol extract was achieved
      with isopropanol extracts. Cytokine protein array revealed Artemisia extracts
      significantly attenuated the levels of CXCL-1, CXCL-16, and MCP-1. These
      orchestrated actions led to significant rescue from SRMD. Conclusively, Artemisia
      extracts imposed significant antioxidant and anti-inflammatory activity against
      SRMD and isopropanol extracts were superior to ethanol extracts in these
      beneficiary actions of Artemisia. 

PMID- 25759520
TI  - Changes in the concentrations of vitamin E analogs and their metabolites in rat
      liver and kidney after oral administration.
AB  - Vitamin E analog, such as alpha- and gamma-tocopherol, can undergo omega
      oxidation without cleavage of the chroman ring, and this pathway is responsible
      for generation of the major urinary vitamin E metabolite, carboxyethyl
      hydroxychroman. However, it is still unclear how carboxyethyl hydroxychroman is
      changed in various tissues after vitamin E intake. We therefore investigated
      changes in the concentrations of alpha- and gamma-tocopherol and their
      metabolites in rat liver and kidney. The concentration of alpha-tocopherol in rat
      liver increased until 6 h after oral administration, and then decreased. The
      change in the concentration of alpha-carboxyethyl hydroxychroman in rat liver in
      the alpha-Toc group slowly increased until 12 h after oral administration.
      Cytochrome P450 3A1 mRNA expression significantly increased from 12 h after the
      start of alpha-tocopherol administration. The change in the concentration of
      gamma-carboxyethyl hydroxychroman in rat liver in the gamma-Toc group markedly
      increased until 12 h after oral administration. On the other hand, gamma
      carboxyethyl hydroxychroman in rat kidney showed greater accumulation than alpha
      carboxyethyl hydroxychroman from 3 h to 24 h after oral administration. From
      these results, we considered that gamma-carboxyethyl hydroxychroman formed in the
      liver continues to be released into the bloodstream and is transported to the
      kidney rapidly. 

PMID- 25759521
TI  - Bacterial cell wall components regulate adipokine secretion from visceral
      adipocytes.
AB  - Recent studies suggest a relationship between intestinal microbiota and metabolic
      syndromes; however, the underlying mechanism remains unclear. To clarify this
      issue, we assessed the effects of bacterial cell wall components on adiponectin,
      leptin and resistin secretion from rat visceral adipocytes in vitro. We also
      measured the relative population of Firmicutes and Bacteroidetes in fecal
      microbiota and the amount of fecal mucin as an intestinal barrier function, when
      mice were fed a high-fat diet. In the present study, we demonstrated that
      bacterial cell wall components affect the secretion of adipokines, depending on
      the presence of antigens from gram-positive or gram-negative bacteria.
      Lipopolysaccharide markedly inhibited adiponectin, leptin, and resistin
      secretion, whereas peptidoglycan increased adiponectin secretion and decreased
      resistin secretion in vitro. In vivo experiments showed that the high-fat diet
      increased the population of Firmicutes and decreased that of Bacteroidetes. In
      contrast, the high-fat diet downregulated the stool output and fecal mucin
      content. These results demonstrate that bacterial cell wall components affect the
      onset of metabolic syndromes by mediating the secretion of adipokines from
      visceral adipose tissue. Furthermore, we believe that metabolic endotoxemia is
      not due to the increasing dominance of gram-negative bacteria, Bacteroidetes, but
      due to the depression of intestinal barrier function. 

PMID- 25759522
TI  - Combined treatment with dipeptidyl peptidase 4 (DPP4) inhibitor sitagliptin and
      elemental diets reduced indomethacin-induced intestinal injury in rats via the
      increase of mucosal glucagon-like peptide-2 concentration.
AB  - The gut incretin glucagon-like peptide-1 (GLP-1) and the intestinotropic hormone
      GLP-2 are released from enteroendocrine L cells in response to ingested
      nutrients. Treatment with an exogenous GLP-2 analogue increases intestinal
      villous mass and prevents intestinal injury. Since GLP-2 is rapidly degraded by
      dipeptidyl peptidase 4 (DPP4), DPP4 inhibition may be an effective treatment for
      intestinal ulcers. We measured mRNA expression and DPP enzymatic activity in
      intestinal segments. Mucosal DPP activity and GLP concentrations were measured
      after administration of the DPP4 inhibitor sitagliptin (STG). Small intestinal
      ulcers were induced by indomethacin (IM) injection. STG was given before IM
      treatment, or orally administered after IM treatment with or without an elemental
      diet (ED). DPP4 mRNA expression and enzymatic activity were high in the jejunum
      and ileum. STG dose-dependently suppressed ileal mucosal enzyme activity.
      Treatment with STG prior to IM reduced small intestinal ulcer scores. Combined
      treatment with STG and ED accelerated intestinal ulcer healing, accompanied by
      increased mucosal GLP-2 concentrations. The reduction of ulcers by ED and STG was
      reversed by co-administration of the GLP-2 receptor antagonist. DPP4 inhibition
      combined with luminal nutrients, which up-regulate mucosal concentrations of GLP
      2, may be an effective therapy for the treatment of small intestinal ulcers. 

PMID- 25759523
TI  - Anti-inflammatory property of propolis.

PMID- 25759524
TI  - Quantitative image analysis of celiac disease.
AB  - We outline the use of quantitative techniques that are currently used for
      analysis of celiac disease. Image processing techniques can be useful to
      statistically analyze the pixular data of endoscopic images that is acquired with
      standard or videocapsule endoscopy. It is shown how current techniques have
      evolved to become more useful for gastroenterologists who seek to understand
      celiac disease and to screen for it in suspected patients. New directions for
      focus in the development of methodology for diagnosis and treatment of this
      disease are suggested. It is evident that there are yet broad areas where there
      is potential to expand the use of quantitative techniques for improved analysis
      in suspected or known celiac disease patients. 

PMID- 25759525
TI  - Hepatosplanchnic circulation in cirrhosis and sepsis.
AB  - Hepatosplanchnic circulation receives almost half of cardiac output and is
      essential to physiologic homeostasis. Liver cirrhosis is estimated to affect up
      to 1% of populations worldwide, including 1.5% to 3.3% of intensive care unit
      patients. Cirrhosis leads to hepatosplanchnic circulatory abnormalities and end
      organ damage. Sepsis and cirrhosis result in similar circulatory changes and
      resultant multi-organ dysfunction. This review provides an overview of the
      hepatosplanchnic circulation in the healthy state and in cirrhosis, examines the
      signaling pathways that may play a role in the physiology of cirrhosis, discusses
      the physiology common to cirrhosis and sepsis, and reviews important issues in
      management. 

PMID- 25759526
TI  - Microscopic enteritis: Bucharest consensus.
AB  - Microscopic enteritis (ME) is an inflammatory condition of the small bowel that
      leads to gastrointestinal symptoms, nutrient and micronutrient deficiency. It is
      characterised by microscopic or sub-microscopic abnormalities such as microvillus
      changes and enterocytic alterations in the absence of definite macroscopic
      changes using standard modern endoscopy. This work recognises a need to
      characterize disorders with microscopic and submicroscopic features, currently
      regarded as functional or non-specific entities, to obtain further understanding
      of their clinical relevance. The consensus working party reviewed statements
      about the aetiology, diagnosis and symptoms associated with ME and proposes an
      algorithm for its investigation and treatment. Following the 5(th) International
      Course in Digestive Pathology in Bucharest in November 2012, an international
      group of 21 interested pathologists and gastroenterologists formed a working
      party with a view to formulating a consensus statement on ME. A five-step
      agreement scale (from strong agreement to strong disagreement) was used to score
      21 statements, independently. There was strong agreement on all statements about
      ME histology (95%-100%). Statements concerning diagnosis achieved 85% to 100%
      agreement. A statement on the management of ME elicited agreement from the lowest
      rate (60%) up to 100%. The remaining two categories showed general agreement
      between experts on clinical presentation (75%-95%) and pathogenesis (80%-90%) of
      ME. There was strong agreement on the histological definition of ME. Weaker
      agreement on management indicates a need for further investigations, better
      definitions and clinical trials to produce quality guidelines for management.
      This ME consensus is a step toward greater recognition of a significant entity
      affecting symptomatic patients previously labelled as non-specific or functional
      enteropathy. 

PMID- 25759527
TI  - Role of periostin and its antagonist PNDA-3 in gastric cancer metastasis.
AB  - The extracellular matrix component periostin is a secreted protein that functions
      as both a cell attachment protein and an autocrine or paracrine factor that
      signals through the cell adhesion molecule integrins alphavbeta3 and alphavbeta5.
      Periostin participates in normal physiological activities such as cardiac
      development, but is also involved in pathophysiological processes in vascular
      diseases, wound repair, bone formation, and tumor development. It is of
      increasing interest in tumor biology because it is frequently overexpressed in a
      variety of epithelial carcinomas and is functionally involved in multiple steps
      of metastasis progression. These include the maintenance of stemness, niche
      formation, EMT, the survival of tumor cells, and angiogenesis, all of which are
      indispensable for gastric cancer metastasis. Periostin has been reported to
      activate the PI-3K/AKT, Wnt, and FAK-mediated signaling pathways to promote
      metastasis. Therefore, periostin represents a potentially promising candidate for
      the inhibition of metastasis. In this review article, we summarize recent
      advances in knowledge concerning periostin, its antagonist PNDA-3, and their
      influence on such key processes in cancer metastasis as maintenance of stemness,
      niche formation, epithelial-to-mesenchymal transition, tumor cell survival, and
      angiogenesis. In particular, we focus our attention on the role of periostin in
      gastric cancer metastasis, speculate as to the usefulness of periostin as a
      therapeutic and diagnostic target for gastric cancer metastasis, and consider
      potential avenues for future research.

PMID- 25759528
TI  - Contrast-enhanced ultrasonography for the evaluation of liver fibrosis after
      biliary obstruction.
AB  - AIM: To investigate perfusion change in contrast-enhanced ultrasonography (CEUS)
      to evaluate liver fibrosis based on biliary obstruction using an animal model.
      METHODS: New Zealand white rabbits (3-4 kg) underwent bile duct ligation to form
      a biliary obstruction model. We performed liver CEUS and laboratory tests on the
      day before the operation (day 0) and every 7 postoperative days until the rabbits
      were sacrificed. After CEUS, signal intensity of liver parenchyma with a time
      intensity curve was analyzed. Perfusion parameters were automatically calculated
      from region-of-interests, including peak signal intensity, mean transit time,
      area under the curve and time to peak. Histological grades of liver fibrosis were
      assessed according to the Metavir score system immediately after sacrifice.
      Generalized estimating equations were used to analyze the association between
      liver fibrosis grades and perfusion parameters for statistical analysis. The
      perfusion parameters were measured on the last day and the difference between day
      0 and the last day were evaluated. RESULTS: From the nine rabbits, histological
      grades of liver fibrosis were grade 1 in one rabbit, grade 2 and 3 in three
      rabbits each, and grade 4 in two rabbits. Among the four CEUS parameters, only
      the peak signal intensity measured on the last day demonstrated a significant
      association with liver fibrosis grades (OR = 1.392, 95%CI: 1.114-1.741, P =
      0.004). The difference in peak signal intensity between day 0 and the last day
      also demonstrated an association with liver fibrosis (OR = 1.191, 95%CI: 0.999
      1.419, P = 0.051). The other parameters tested, including mean transit time, area
      under the curve, and time to peak, showed no significant correlation with liver
      fibrosis grades. CONCLUSION: This animal study demonstrates that CEUS can be used
      to evaluate liver fibrosis from biliary obstruction using peak signal intensity
      as a parameter.

PMID- 25759529
TI  - Isolation and diagnosis of Helicobacter pylori by a new method: microcapillary
      culture.
AB  - AIM: To investigate the performance of the microcapillary culture method (MCM) in
      Helicobacter pylori (H. pylori) isolation and diagnosis. METHODS: Microcapillary
      culture (MC), classical culture (CC), rapid urease (CLO) test, and
      histopathologic examination (HE) were performed with biopsy samples. Homogenized
      biopsy samples were loaded into capillary tubes and incubated for 48 h at 37 
      degrees C without providing a microaerophilic environment. Additionally, three or
      four loops of the homogenized sample were inoculated in a ready-to-use selective
      medium (Becton Dickinson, Helicobacter Agar, Modified) specific for the isolation
      of H. pylori and incubated at 37  degrees C in a microaerophilic atmosphere
      provided by CampyGen (Becton Dickinson, GasPack). Bacteria reproducing in
      microcapillary tubes were evaluated in an inverted microscope and also were
      evaluated after performing a CC with the content. Results obtained by CC, CLO
      test, and HE were compared with those of MC. The diagnostic performances of the
      methods used in this study were evaluated for specificity, sensitivity, positive
      predictive value (PPV), negative predictive value (NPV), and CI. RESULTS: H.
      pylori was found positive by CLO test + HE and/or CC culture in 26 patient antrum
      and corpus biopsy samples. In 25 (25/26) patient biopsy samples, H. pylori was
      isolated by MCM, whereas in only 14 (14/26) patient biopsy samples, H. pylori was
      isolated by CC. CLO test and HE were found positive in 17 (17/26) patient biopsy
      samples. Comparing the results of the isolation of H. pylori by MCM, CC, CLO
      test, and HE, the sensitivity of the MCM was found as 96%, the specificity as
      80%, the PPV as 83%, the NPV as 95%, and the 95%CI as 0.76 (chi (2) = 31.51, P <
      0.01) whereas the sensitivity of the CC was found as 54% (chi (2) = 19.15, P <
      0.01), and the sensitivity of the CLO test and HE were found as 65% (chi (2) =
      25.26, P < 0.01). CONCLUSION: This new microcapillary cultivation method for H.
      pylori has high diagnostic sensitivity compared with CC, HE, and CLO tests.

PMID- 25759530
TI  - Combined detection of plasma GATA5 and SFRP2 methylation is a valid noninvasive
      biomarker for colorectal cancer and adenomas.
AB  - AIM: To investigate GATA5, SFRP2, and ITGA4 methylation in plasma DNA as
      noninvasive biomarkers for colorectal cancer (CRC) or adenomas. METHODS: There
      were 57 CRC patients, 30 adenomas patients, and 47 control patients enrolled in
      this study. Methylation-specific polymerase chain reaction was used to determine
      the promoter methylation status of GATA5, SFRP2, and ITGA4 genes in plasma DNA,
      and their association with clinical outcome in CRC. The predictive ability of
      GATA5, SFRP2, and ITGA4 methylation, individually or in combination, to detect
      CRC or adenomas was further analyzed. RESULTS: Hypermethylated GATA5 was detected
      in plasma in 61.4% (35/57) of CRC cases, 43.33% (13/30) of adenoma cases, and
      21.28% (10/47) of control cases. The hypermethylation of SFRP2 was detected in
      54.39% (31/57), 40.00% (12/30), and 27.66% (13/47) in plasma samples from CRC,
      adenomas, and controls, respectively. ITGA4 methylation was detected in 36.84%
      (21/57) of plasma samples of CRC patients and in 30.00% (9/30) of plasma samples
      from patients with colorectal adenomas, and the specificity of this individual
      biomarker was 80.85% (9/47). Moreover, GATA5 methylation in the plasma was
      significantly correlated with larger tumor size (P = 0.019), differentiation
      status (P = 0.038), TNM stage (P = 0.008), and lymph node metastasis (P = 0.008).
      SFRP2 and ITGA4 methylation in plasma significantly correlated with
      differentiation status (SFRP2, P = 0.012; ITGA4, P = 0.007), TNM stage (SFRP2, P
      = 0.034; ITGA4, P = 0.021), and lymph node metastasis (SFRP2, P = 0.034; ITGA4, P
      = 0.021). From the perspective of predictive power and cost-performance, using
      GATA5 and SFRP2 together as methylation markers seemed the most favorable
      predictor for CRC (OR = 8.06; 95%CI: 2.54-25.5; P < 0.01) and adenomas (OR =
      3.35; 95%CI: 1.29-8.71; P = 0.012). CONCLUSION: A combination of GATA5 and SFRP2
      methylation could be promising as a marker for the detection and diagnosis of CRC
      and adenomas.

PMID- 25759531
TI  - Effect of bifidobacterium on defensin-5 expression in intestinal injury of
      preweaning rats.
AB  - AIM: To investigate the protective effect of bifidobacterium in endotoxin-induced
      intestinal injury in preweaning rats. METHODS: Preweaning rats were randomly
      divided into three groups (n = 40 for each): a control group (group C), a model
      group (group E) and a treatment group (group T). Both groups E and T were
      intraperitoneally injected with lipopolysaccharide (LPS) at a dose of 5 mg/kg (5
      mg/L in normal saline), and group T was intragastrically administrated with
      bifidobacterium suspension (2.0 * 10(9) CFU/mL, 0.5 mL each time, twice a day,
      until the end of the experiment) 7 d before LPS administration. Group C was
      intraperitoneally injected with normal saline. After intraperitoneal injection
      and intragastric administration, the rats were placed back to the initial cage to
      receive breast feeding. The rats were killed at 2, 6, 12, 24 or 72 h,
      respectively, after endotoxin or physiological saline injection to collect serum
      and ileal tissue samples. Myeloperoxidase (MPO) contents in serum and ileum were
      detected at different times, and expression of ileal defensin-5 mRNA was
      evaluated by reverse transcription-polymerase chain reaction. RESULTS: Serum and
      ileal MPO contents in group E were significantly higher than those in group C
      (serum contents: 107.50 +/- 17.70 vs 157.14 +/- 24.67, P < 0.05; ileal contents:
      1.03 +/- 0.21 vs 1.57 +/- 0.33, P < 0.05), which peaked at 12 h and 6 h,
      respectively. MPO contents in group T were significantly lower than those in
      group E (serum contents: 114.38 +/- 24.56 vs 145.25 +/- 23.62, P < 0.05; ileal
      contents: 1.25 +/- 0.24 vs 1.57 +/- 0.33, P < 0.05). The expression of defensin-5
      mRNA in group E was significantly higher than that in group C (0.953 +/- 0.238 vs
      0.631 +/- 0.146, P < 0.05), which peaked at 2 h, and then decreased gradually.
      The expression of defensin-5 mRNA in group T was significantly lower than that in
      group E (0.487 +/- 0.149 vs 0.758 +/- 0.160, P < 0.05) apparently in 24 h. The
      expression of defensin-5 mRNA at 2 h in group T was significantly higher than
      that in group C (0.824 +/- 0.158 vs 0.631 +/- 0.146, P < 0.05). CONCLUSION: MPO
      and defensin-5 mRNA increase in preweaning rats with LPS-induced intestinal
      injury. Bifidobacterium protects the gut by inhibiting MPO activity, not by
      increasing defensin-5 secretion.

PMID- 25759532
TI  - Angiopoietin and vascular endothelial growth factor expression in colorectal
      disease models.
AB  - AIM: To investigate angiopoietin (Ang) and vascular endothelial growth factor
      (VEGF) expression in rats with ulcerative colitis (UC) and colorectal cancer
      (CRC). METHODS: Dysplasia and cancer were investigated in rats that received
      three cycles of 3.5% dextran sulfate sodium (DSS) in drinking water for 7 d
      followed by distilled water for 14 d after intraperitoneal pretreatment with 20
      mg/kg 1,2-dimethylhydrazine (DMH) (CRC group). Colitis was investigated in rats
      that received three cycles of 3.5% DSS in drinking water for 7 d followed by
      distilled water for 14 d after intraperitoneal pretreatment with saline (UC
      group). Rats without DSS or DMH treatment served as controls. Expression of the
      tyrosine kinase with immunoglobulin-like and EGF-like domains (Tie)-2 and its
      ligands, Ang-1 and Ang-2, as well as VEGF were evaluated in the colorectum by
      Western blotting. RESULTS: Compared with rats in the control group, rats in the
      CRC and UC groups developed the symptoms of acute colitis with diarrhea, rectal
      bleeding, wasting, and loss of body weight (P < 0.05). In addition, the mean
      length of colorectum of CRC and UC rats was significantly shorter than that of
      control rats (8.29 +/- 0.21 and 8.31 +/- 0.86, respectively, vs 12.34 +/- 0.12
      cm; P < 0.05). Furthermore, rats in the CRC group, but not in the UC or control
      groups, developed multiple tumors in the colorectal region. Western blot analysis
      revealed that rats in the CRC and UC groups had markedly increased protein levels
      of Ang-1, Ang-2, Tie-2, and VEGF in the colorectum compared to rats in the
      control group. CONCLUSION: Increased expression of Ang-1, Ang-2, Tie-2, and VEGF
      in ulcerative colitis-derived colorectal cancer might lead to chronic colitis and
      pathologic angiogenesis in rats.

PMID- 25759533
TI  - Are gastric mucosal macrophages responsible for gastric injury in acute
      pancreatitis?
AB  - AIM: To investigate the protective effect of clodronate-containing liposomes
      against severe acute pancreatitis (SAP)-triggered acute gastric mucosal injury
      (AGMI) in rats. METHODS: Clodronate- and phosphate-buffered saline (PBS)
      containing liposomes were prepared by reverse-phase evaporation. The SAP rat
      model was established by injecting sodium taurocholate into the pancreatic
      subcapsular space. Sprague-Dawley rats were randomly divided into three groups:
      control (C), SAP plus PBS-containing liposome (P) and SAP plus clodronate
      containing liposome (T). Serum tumor necrosis factor (TNF)-alpha levels were
      estimated by ELISA. Pathological changes in the gastric mucosa and pancreas were
      observed by hematoxylin and eosin (HE) staining. Apoptotic cells were detected by
      terminal deoxynucleotidyl transferase dUTP nick end labeling staining. The
      numbers of macrophages in the gastric mucosa were analyzed by CD68
      immunohistochemical staining. RESULTS: The liposomes had a mean diameter of 150
      +/- 30 nm. The TNF-alpha levels were significantly higher in the P group than
      that in the C group (2 h, 145.13 +/- 11.50 vs 23.2 +/- 2.03; 6 h, 245.06 +/-
      12.11 vs 30.28 +/- 6.07, P < 0.05), and they were significantly lower in the T
      group than that in the P group (2 h, 93.24 +/- 23.11 vs 145.13 +/- 11.50; 6 h,
      135.18 +/- 13.10 vs 245.06 +/- 12.11, P < 0.05). The pathological scores of the
      pancreas were lower in the T group than in the P group (2 h, 1.88 +/- 0.83 vs
      4.13 +/- 0.83; 6 h, 2.87 +/- 0.64 vs 6.25 +/- 0.88, P < 0.01). The pathological
      scores of the gastric mucosa were also lower in the T group than in the P group
      (2 h, 1.12 +/- 0.64 vs 2 +/- 0.75; 6 h, 1.58 +/- 0.53 vs 3 +/- 1.31, P < 0.05).
      In addition, increased CD68 levels were observed in the gastric mucosa of the P
      group compared with the C group. Clodronate-containing liposomes decreased the
      CD68 levels in the mucosa of the T group. The apoptotic indexes of the gastric
      mucosa were higher in the T group than in the P group (2 h, 15.7 +/- 0.92 vs 11.5
      +/- 1.64; 6 h, 21.12 +/- 1.06 vs 12.6 +/- 2.44, P < 0.01). CONCLUSION: Gastric
      macrophages contribute to the pathogenesis of gastric injury in SAP. Clodronate
      containing liposomes have protective effects against AGMI in rats with SAP.

PMID- 25759534
TI  - Outcomes of nonresected main-duct intraductal papillary mucinous neoplasms of the
      pancreas.
AB  - AIM: To compare characteristics and outcomes of resected and nonresected main
      duct and mixed intraductal papillary mucinous neoplasms of the pancreas (IPMN).
      METHODS: Over a 14-year period, 50 patients who did not undergo surgery for
      resectable main-duct or mixed IPMN, for reasons of precluding comorbidities, age
      and/or refusal, were compared with 74 patients who underwent resection to assess
      differences in rates of survival, recurrence/occurrence of malignancy, and
      prognostic factors. All study participants had dilatation of the main pancreatic
      duct by >= 5 mm, with or without dilatation of the branch ducts. Some of the
      nonsurgical patients showed evidence of mucus upon perendoscopic retrograde
      cholangiopancreatography or endoscopic ultrasound and/or after fine needle
      aspiration. For the surgical patients, pathologic analysis of resected specimens
      confirmed a diagnosis of IPMN with involvement of the main pancreatic duct or of
      both branch ducts as well as the main pancreatic duct. Clinical and biologic
      follow-ups were conducted for all patients at least annually, through
      hospitalization or consultation every six months during the first year of follow
      up, together with abdominal imaging analysis (magnetic resonance
      cholangiopancreatography or computed tomography) and, if necessary, endoscopic
      ultrasound with or without fine needle aspiration. RESULTS: The overall five-year
      survival rate of patients who underwent resection was significantly greater than
      that for the nonsurgical patients (74% vs 58%; P = 0.019). The parameters of age
      (< 70 years) and absence of a nodule were associated with better survival (P <
      0.05); however, the parameters of main pancreatic duct diameter > 10 mm, branch
      duct diameter > 30 mm, or presence of extra pancreatic cancers did not
      significantly influence the prognosis. In the nonsurgical patients, pancreatic
      malignancy occurred in 36% of cases within a mean time of 33 mo (median: 29 mo;
      range: 8-141 mo). Comparison of the nonsurgical patients who experienced disease
      progression with those who did not progress showed no significant differences in
      age, sex, symptoms, subtype of IPMN, or follow-up period; only the size of the
      main pancreatic duct was significantly different between these two sub-groups,
      with the nonsurgical patients who experienced progression showing a greater
      diameter at the time of diagnosis (> 10 mm). CONCLUSION: Patients unfit for
      surgery have a 36% greater risk of developing pancreatic malignancy of the main
      duct or mixed IPMN within a median of 2.5 years.

PMID- 25759535
TI  - Absolute monocyte and lymphocyte count prognostic score for patients with gastric
      cancer.
AB  - AIM: To measure the prognostic significance of absolute monocyte count/absolute
      lymphocyte count prognostic score (AMLPS) in patients with gastric cancer.
      METHODS: We retrospectively examined the combination of absolute monocyte count
      (AMC) and absolute lymphocyte count (ALC) as prognostic variables in a cohort of
      299 gastric cancer patients who underwent surgical resection between 2006 and
      2013 and were followed at a single institution. Both AMC and ALC were
      dichotomized into two groups using cut-off points determined by receiving
      operator characteristic curve analysis. An AMLPS was generated, which stratified
      patients into three risk groups: low risk (both low AMC and high ALC),
      intermediate risk (either high AMC or low ALC), and high risk (both high AMC and
      low ALC). The primary objective of the study was to validate the impact of AMLPS
      on both disease-free survival (DFS) and overall survival (OS), and the second
      objective was to assess the AMLPS as an independent prognostic factor for
      survival in comparison with known prognostic factors. RESULTS: Using data from
      the entire cohort, the most discriminative cut-off values of AMC and ALC selected
      on the receiver operating characteristic curve were 672.4/MUL and 1734/MUL for
      DFS and OS. AMLPS risk groups included 158 (52.8%) patients in the low-risk, 128
      (42.8%) in the intermediate-risk, and 13 (4.3%) in the high-risk group. With a
      median follow-up of 37.2 mo (range: 1.7-91.4 mo), five-year DFS rates in the low
      , intermediate-, and high-risk groups were 83.4%, 78.7%, and 19.8%, respectively.
      And five-year OS rates in the low-, intermediate-, and high-risk groups were
      89.3%, 81.1%, and 14.4%, respectively. On multivariate analysis performed with
      patient- and tumor-related factors, we identified AMLPS, age, and pathologic
      tumor-node-metastasis stage as the most valuable prognostic factors impacting DFS
      and OS. CONCLUSION: AMLPS identified patients with a poor DFS and OS, and it was
      independent of age, pathologic stage, and various inflammatory markers.

PMID- 25759536
TI  - Effect of longer battery life on small bowel capsule endoscopy.
AB  - AIM: To determine if longer battery life improves capsule endoscopy (CE)
      completion rates. METHODS: A retrospective study was performed at a tertiary,
      university-affiliated hospital in Vancouver, Canada. Patients who underwent CE
      with either PillCamTM SB2 or SB2U between 01/2010 and 12/2013 were considered for
      inclusion. SB2 and SB2U share identical physical dimensions but differ in their
      battery lives (8 h vs 12 h). Exclusion criteria included history of gastric or
      small bowel surgery, endoscopic placement of CE, interrupted view of major
      landmarks due to technical difficulty or significant amount of debris, and repeat
      CE using same system. Basic demographics, comorbidities, medications, baseline
      bowel habits, and previous surgeries were reviewed. Timing of major landmarks in
      CE were recorded, and used to calculate gastric transit time, small bowel transit
      time, and total recording time. A complete CE study was defined as visualization
      of cecum. Transit times and completion rates were compared. RESULTS: Four hundred
      and eight patients, including 208 (51.0%) males, were included for analysis. The
      mean age was 55.5 +/- 19.3 years. The most common indication for CE was
      gastrointestinal bleeding (n = 254, 62.3%), followed by inflammatory bowel
      disease (n = 86, 21.1%). There was no difference in gastric transit times (group
      difference 0.90, 95%CI: 0.72-1.13, P = 0.352) and small bowel transit times
      (group difference 1.07, 95%CI: 0.95-1.19, P = 0.261) between SB2U and SB2, but
      total recording time was about 14% longer in the SB2U group (95%CI: 10%-18%, P <
      0.001) and there was a corresponding trend toward higher completion rate (88.2%
      vs 93.2%, OR = 1.78, 95%CI 0.88-3.63, P = 0.111). There was no statistically
      significant difference in the rates of positive findings (OR = 0.98, 95%CI: 0.64
      1.51, P = 0.918). CONCLUSION: Extending the operating time of CE may be a simple
      method to improve completion rate although it does not affect the rate of
      positive findings.

PMID- 25759537
TI  - Stratifying the risk of lymph node metastasis in undifferentiated-type early
      gastric cancer.
AB  - AIM: To study how lymph node metastasis (LNM) risk is stratified in
      undifferentiated-type early gastric cancer (undiff-EGC) dependent on combinations
      of risk factors. METHODS: Five hundred and sixty-seven cases with undiff-EGC
      undergoing gastrectomy with lymphadenectomy were examined retrospectively. Using
      clinicopathological factors of patient age, location, size, an endoscopic
      macroscopic tumor form, ulceration, depth, histology, lymphatic involvement (LI)
      and venous involvement (VI), LNM risk was examined and stratified by conventional
      statistical analysis and data-mining analysis. RESULTS: LNM was positive in 44 of
      567 cases (7.8%). Univariate analysis revealed > 2 cm, protrusion, submucosal
      (sm), mixed type, LI and VI as significant prognostic factors and > 2 cm and LI
      positive were independent factors by multivariate analysis. In preoperatively
      evaluable factors excluding LVI, sm and > 2 cm were independent factors.
      According to the depth and size, cases were categorized into the low-risk group
      [m and <= 2 cm, 0% (LNM incidence)], the moderate-risk group (m and > 2 cm, 5.6%;
      and sm and <= 2 cm, 6.0%), and the high-risk group (sm and > 2 cm, 19.3%). On the
      other hand, LNM occurred in 1.4% in all LI-negative cases, greatly lower than
      28.2% in all LI-positive cases, and LNM incidence was low in LI-negative cases
      even in the moderate- and high-risk groups. CONCLUSION: LNM-related factors in
      undiff-EGC were depth and size preoperatively while those were LI and size
      postoperatively. Among these factors, LI was the most significantly correlated
      factor.

PMID- 25759538
TI  - Clinical usefulness of endoscopic ultrasonography for the evaluation of
      ulcerative colitis-associated tumors.
AB  - AIM: To evaluate the clinical usefulness of endoscopic ultrasonography (EUS) for
      the diagnosis of the invasion depth of ulcerative colitis-associated tumors.
      METHODS: The study group comprised 13 patients with 16 ulcerative colitis (UC)
      associated tumors for which the depth of invasion was preoperatively estimated by
      EUS. The lesions were then resected endoscopically or by surgical colectomy and
      were examined histopathologically. The mean age of the subjects was 48.2 +/- 17.1
      years, and the mean duration of UC was 15.8 +/- 8.3 years. Two lesions were
      treated by endoscopic resection and the other 14 lesions by surgical colectomy.
      The depth of invasion of UC-associated tumors was estimated by EUS using an
      ultrasonic probe and was evaluated on the basis of the deepest layer with
      narrowing or rupture of the colonic wall. RESULTS: The diagnosis of UC-associated
      tumors by EUS was carcinoma for 13 lesions and dysplasia for 3 lesions. The
      invasion depth of the carcinomas was intramucosal for 8 lesions, submucosal for
      2, the muscularis propria for 2, and subserosal for 1. Eleven (69%) of the 16
      lesions arose in the rectum. The macroscopic appearance was the laterally
      spreading tumor-non-granular type for 4 lesions, sessile type for 4, laterally
      spreading tumor-granular type for 3, semi-pedunculated type (Isp) for 2, type 1
      for 2, and type 3 for 1. The depth of invasion was correctly estimated by EUS for
      15 lesions (94%) but was misdiagnosed as intramucosal for 1 carcinoma with high
      grade submucosal invasion. The 2 lesions treated by endoscopic resection were
      intramucosal carcinoma and dysplasia, and both were diagnosed as intramucosal
      lesions by EUS. CONCLUSION: EUS provides a good estimation of the invasion depth
      of UC-associated tumors and may thus facilitate the selection of treatment.

PMID- 25759539
TI  - Mucinous phenotype and CD10 expression of primary adenocarcinoma of the small
      intestine.
AB  - AIM: To clarify the correlation with phenotypic expression, clinicopathological
      features, genetic alteration and microsatellite-instability status in small
      intestinal adenocarcinoma (SIA). METHODS: The cases of 47 patients diagnosed with
      primary SIAs that were surgically resected at our institution in 1975-2005 were
      studied. We reviewed clinicopathological findings (age, gender, tumor size, gross
      appearance, histological morphologic type, invasion depth, lymphatic permeation,
      venous invasion, and lymph node metastasis), and the immunohistochemical
      expression of MUC5AC, MUC6, MUC2, CD10, and mismatch-repair (MMR) proteins (MLH1
      and MSH2). We analyzed KRAS and BRAF gene mutations, and the microsatellite
      instability (MSI) status. The immunohistochemical staining of CD10, MUC2, MUC5AC
      and MUC6 was considered positive when distinct staining in > 5% of the
      adenocarcinoma cells was recorded. To evaluate of MMR protein expression, we used
      adjacent normal tissue including lymphoid follicles, inflammatory cells, and
      stromal cells as an internal positive control. Sections without nuclear staining
      in the tumor cells were considered to have lost the expression of the respective
      MMR protein. RESULTS: There were 29 males and 18 females patients (mean age 59.9
      years, range: 23-87 years). Tumors were located in the duodenum in 14 cases
      (30%), the jejunum in 21 cases (45%), and the ileum in 12 cases (25%). A
      phenotypic expression analysis revealed 20 MUC2-positive tumors (42.6%), 11
      MUC5AC-positive (23.4%), 4 MUC6-positive (8.5%), and 7 CD10-positive (14.9%). The
      tumor sizes of the MUC2(+) tumors were significantly larger than those of the
      MUC2(-) tumors (mean, 5.7 +/- 1.4 cm vs 4.7 +/- 2.1 cm, P < 0.05). All three
      tumors with adenomatous component were positive for MUC2 (P < 0.05). Polypoid
      appearance was seen significantly more frequently in the CD10(+) group than in
      the CD10(-) group (P < 0.05). The tumor size was significantly larger in the CD10
      (+) group than in the CD10(-) group (mean, 5.9 +/- 1.4 cm vs 5.0 +/- 2.1 cm, P <
      0.05). Of 34 SIAs with successfully obtained MSI data, 4 were MSI-high. Of the 4
      SIAs positive for both MUC5AC and MUC2, 3 showed MSI-H (75%) and 3 were mucinous
      adenocarcinoma (75%). KRAS mutations were detected in 4 SIAs. SIAs had KRAS
      mutation expressed only MUC2, but were negative for MUC5AC, MUC6 and CD10.
      CONCLUSION: These findings suggest that the phenotypic expression of SIAs is
      correlated with their biological behavior, genetic alteration, and MSI status.

PMID- 25759540
TI  - Neoadjuvant chemoradiotherapy followed by D2 gastrectomy in locally advanced
      gastric cancer.
AB  - AIM: To investigate the efficacy of neoadjuvant chemoradiotherapy (NACRT) for
      resectability of locally advanced gastric cancer (LAGC). METHODS: Between
      November 2007 and January 2014, 29 patients with LAGC (clinically T3 with distal
      esophagus invasion/T4 or bulky regional node metastasis) that were treated with
      NACRT followed by D2 gastrectomy were included in this study. Resectability was
      evaluated with radiologic and endoscopic exams before and after NACRT. Using
      three-dimensional conformal radiotherapy, patients received 45 Gy, with a daily
      dose of 1.8 Gy. The entire tumor extent and the regional metastatic lymph nodes
      were included in the gross tumor volume. Patients presenting with a resectable
      tumor after NACRT received a total or subtotal gastrectomy with D2 dissection.
      The pathologic tumor response was evaluated using Japanese Gastric Cancer
      Association histologic evaluation criteria. Postoperative morbidity was evaluated
      using the National Cancer Institute-Common Terminology Criteria for Adverse
      Events version 4.0. Overall survival (OS) and progression-free survival (PFS)
      rates were estimated using a Kaplan-Meier analysis and compared using the log
      rank test. RESULTS: All patients were assessed as unresectable cases. Twenty-four
      patients (24/29; 82.8%) showed LAGC on positron emission tomography-computed
      tomography (CT) and contrast-enhanced CT, whereas four patients (4/29; 13.8%)
      with vague invasion or abutment to an adjacent organ underwent diagnostic
      laparoscopy. One patient (1/29; 3.4%), initially assessed as a resectable case,
      underwent an "open and closure" after the tumor was found to be unresectable.
      Abutment to an adjacent organ (34.5%) was the most common reason for NACRT. The
      clinical response rate one month after NACRT was 44.8%. After NACRT, 69% (20/29)
      of patients had a resectable tumor. Of the 20 patients with a resectable tumor,
      18 patients (62.1%) underwent a D2 gastrectomy. The R0 resection rate was 94.4%
      and two patients (2/18; 11.1%) showed a complete response. The median follow-up
      duration was 13.5 mo. The one-year OS and PFS rates were 72.4 and 48.9%,
      respectively. The one-year OS, PFS, local failure-free survival, and distant
      metastasis-free survival were higher in patients with a resectable tumor after
      NACRT (P < 0.001, P < 0.001, P < 0.001, and P = 0.078, respectively). No grade 3
      4 late treatment-related toxicities or postoperative mortalities were observed.
      CONCLUSION: NACRT with D2 gastrectomy showed a high rate of R0 resection and
      promising local control, which may increase the R0 resection opportunity
      resulting in survival benefit.

PMID- 25759541
TI  - Endoscopic cyanoacrylate injection for the treatment of gastric varices in
      children.
AB  - AIM: To evaluate the efficacy and safety of N-butyl-2-cyanoacrylate in treating
      acute bleeding of gastric varices in children. METHODS: The retrospective study
      included 21 children with 47 episodes of active gastric variceal bleeding who
      were treated by endoscopic injection of N-butyl-2-cyanoacrylate at Asan Medical
      Center Children's Hospital between August 2004 and December 2011. To reduce the
      risk of embolism, each injection consisted of 0.1-0.5 mL of 0.5 mL N-butyl-2
      cyanoacrylate diluted with 0.5 or 0.8 mL Lipiodol. The primary outcome was
      incidence of hemostasis after variceal obliteration and the secondary outcome was
      complication of the procedure. RESULTS: The 21 patients experienced 47 episodes
      of active gastric variceal bleeding, including rebleeding, for which they
      received a total of 52 cyanoacrylate injections. Following 42 bleeding episodes,
      hemostasis was achieved after one injection and following five bleeding episodes
      it was achieved after two injections. The mean volume of each single aliquot of
      cyanoacrylate injected was 0.3 +/- 0.1 mL (range: 0.1-0.5 mL). Injection achieved
      hemostasis in 45 of 47 (95.7%) episodes of acute gastric variceal bleeding.
      Eleven patients (52.4%) developed rebleeding events, with the mean duration of
      hemostasis being 11.1 +/- 11.6 mo (range: 1.0-39.2 mo). No treatment-related
      complications such as distal embolism were noted with the exception of abdominal
      pain in one patient (4.8%). Among four mortalities, one patient died of variceal
      rebleeding. CONCLUSION: Endoscopic variceal obliteration using a small volume of
      aliquots with repeated cyanoacrylate injection was an effective and safe option
      for the treatment of gastric varices in children.

PMID- 25759542
TI  - Feasibility and safety of using Soehendra stent retriever as a new technique for
      biliary access in endoscopic ultrasound-guided biliary drainage.
AB  - AIM: To assess the feasibility and safety of the use of soehendra stent retriever
      as a new technique for biliary access in endoscopic ultrasound-guided biliary
      drainage. METHODS: The medical records and endoscopic reports of the patients who
      underwent endoscopic ultrasound-guided biliary drainage (EUS-BD) owing to failed
      endoscopic retrograde cholangiopancreatography in our institute between June 2011
      and January 2014 were collected and reviewed. All the procedures were performed
      in the endoscopic suite under intravenous sedation with propofol and full
      anaesthetic monitoring. Then we used the Soehendra stent retriever as new
      equipment for neo-tract creation and dilation when performing EUS-BD procedures.
      The patients were observed in the recovery room for 1-2 h and transferred to the
      regular ward, patients' clinical data were reviewed and analysed, clinical
      outcomes were defined by using several different criteria. Data were analysed by
      using SPSS 13 and presented as percentages, means, and medians. RESULTS: A total
      of 12 patients were enrolled. The most common indications for EUS-BD in this
      series were failed common bile duct cannulation, duodenal obstruction, failed
      selective intrahepatic duct cannulation, and surgical altered anatomy for 50%,
      25%, 16.7%, and 8.3%, respectively. Seven patients underwent EUS-guided
      hepaticogastrostomy (58.3%), and 5 underwent EUS-guided choledochoduodenostomy
      (41.7%). The technical success rate was 100%, while the clinical success rate was
      91.7%. Major and minor complications occurred in 16.6% and 33.3% of patients,
      respectively, but there were no procedure-related death. CONCLUSION: Soehendra
      stent retriever could be used as an alternative instrument for biliary access in
      endoscopic ultrasound guided biliary drainage.

PMID- 25759543
TI  - Continuous suture of the pancreatic stump and Braun enteroenterostomy in
      pancreaticoduodenectomy.
AB  - AIM: To investigate a new modification of pancreaticoduodenectomy (PD)-a mesh
      like running suturing of the pancreatic remnant and Braun's enteroenterostomy.
      METHODS: Two hundred and three patients underwent PD from 2009 to 2014 and were
      classified into two groups: Group A (98 patients), who received PD with a mesh
      like running suturing for the pancreatic remnant, and Braun's enteroenterostomy;
      and Group B (105 patients), who received standard PD. Demographic data,
      intraoperative findings, postoperative morbidity and perioperative mortality
      between the two groups were compared by univariate and multivariate analysis.
      RESULTS: Demographic characteristics between Group A and Group B were comparable.
      There were no significant differences between the two groups concerning
      perioperative mortality, and operative blood loss, as well as the incidence of
      the postoperative morbidity, including reoperation, bile leakage, intra-abdominal
      fluid collection or infection, and postoperative bleeding. Clinically relevant
      postoperative pancreatic fistula (POPF) and delayed gastric emptying (DGE) were
      identified more frequently in Group B than in Group A. Technique A (PD with a
      mesh-like running suturing of the pancreatic remnant and Braun's
      enteroenterostomy) was independently associated with decreased clinically
      relevant POPF and DGE, with an odds ratio of 0.266 (95%CI: 0.109-0.654, P =
      0.004) for clinically relevant POPF and 0.073 (95%CI: 0.010-0.578, P = 0.013) for
      clinically relevant DGE. CONCLUSION: An additional mesh-like running suturing of
      the pancreatic remnant and Braun's enteroenterostomy during PD decreases the
      incidence of postoperative complications and is beneficial for patients.

PMID- 25759544
TI  - Evaluation of changes of serum hepatitis B surface antigen from a different
      perspective.
AB  - AIM: To investigate the dynamic changes of serum hepatitis B surface antigen
      (HBsAg) levels apportioned by the same hepatic parenchyma cell volume (HPCV),
      namely, hepatic cell quantities. METHODS: Serum HBsAg levels were detected by
      electrochemiluminescence and serum HBsAg levels apportioned by the same HPCV were
      figured out according to the theory of sphere geometry. HBsAg levels were
      compared among different liver inflammation grades, as well as different hepatic
      fibrosis stages. RESULTS: In hepatitis B e antigen-negative chronic hepatitis B,
      serum HBsAg levels in liver histological inflammation grades 1-4 were 3.66 +/-
      0.40, 3.74 +/- 0.35, 3.74 +/- 0.26 and 3.71 +/- 0.34 log10 COI (cut off index),
      respectively, and there were no differences before apportion (P = 0.640). Serum
      HBsAg levels apportioned by the same HPCV were 5.57 +/- 0.62, 5.98 +/- 0.65, 6.59
      +/- 0.50 and 6.81 +/- 0.84 log10 COI, respectively, and there were significant
      differences after apportion (P < 0.001). Serum HBsAg levels in hepatic fibrosis
      stages I-IV were 3.66 +/- 0.43, 3.75 +/- 0.33, 3.71 +/- 0.28 and 3.75 +/- 0.26
      log10 COI, respectively, and there were no differences before apportion (P =
      0.513). Serum HBsAg levels apportioned by the same HPCV were 5.53 +/- 0.66, 5.98
      +/- 0.53, 6.29 +/- 0.46 and 7.06 +/- 0.48 log10 COI, respectively, and there were
      significant differences after apportion (P < 0.001). CONCLUSION: Serum HBsAg
      levels apportioned by the same HPCV (hepatic cell quantities), rather than serum
      HBsAg levels, increase with liver inflammation grades and hepatic fibrosis
      stages.

PMID- 25759545
TI  - Tenofovir disoproxil fumarate is superior to lamivudine plus adefovir in
      lamivudine-resistant chronic hepatitis B patients.
AB  - AIM: To assess the efficacy of tenofovir disoproxil fumarate (TDF) in lamivudine
      (LAM)-resistant patients with a suboptimal response to LAM plus adefovir (ADV).
      METHODS: We retrospectively analyzed the efficacy of switching to tenofovir
      disoproxil fumarate in suboptimal responders to lamivudine plus adefovir. Charts
      were reviewed for LAM-resistant chronic hepatitis B (CHB) patients who visited
      the Zhejiang Province People's Hospital and The First Affiliated Hospital,
      College of Medicine, Zhejiang University, from June 2009 to May 2013. Patients
      whose serum hepatitis B virus (HBV) DNA remained detectable despite at least 6 mo
      of LAM plus ADV combination therapy were included. Patients with a suboptimal
      response to LAM plus ADV were randomized to switch to TDF monotherapy (300 mg/d
      orally; TDF group) or to continuation with LAM (100 mg/d orally) plus ADV (10
      mg/d orally; LAM plus ADV group) and were followed for 48 wk. Serum HBV DNA was
      determined at baseline and weeks 4, 12, 24, 36, and 48. HBV serological markers
      and biochemistry were assessed at baseline and weeks 12, 24, and 48. Resistance
      surveillance and side effects were monitored during therapy. RESULTS: Fifty-nine
      patient were randomized to switch to TDF (n = 28) or continuation with LAM plus
      ADV (n = 31). No significant differences were found between the groups at
      baseline. Prior to TDF therapy, all patients had been exposed to LAM plus ADV for
      a median of 11 mo (range: 6-24 mo). No difference was seen in baseline serum HBV
      DNA between the two groups [5.13 +/- 1.08 log10 copies/mL (TDF) vs 5.04 +/- 31.16
      log10 copies/mL (LAM + ADV), P = 0.639]. There was no significant difference in
      the rates of achieving complete virological response (CVR) at week 4 between the
      TDF and LAM + ADV groups (17.86% vs 6.45%, P = 0.24). The rate of achieving CVR
      in the TDF and LAM plus ADV groups was 75% vs 16.13% at week 12, 82.14% vs 22.58%
      at week 24, 89.29% vs 25.81% at week 36, and 96.43% vs 29.03% at week 48,
      respectively (P < 0.001). The rate of alanine aminotransferase normalization was
      significantly higher in the TDF than in the LAM plus ADV group at week 12 (75% vs
      17.86%, P < 0.001), but not at week 24 (78.57% vs 54.84%, P = 0.097) or 48
      (89.26% vs 67.74%, P = 0.062). Patients were hepatitis B e antigen (HBeAg)
      positive at baseline. There was no significant difference in HBeAg negativity
      between the TDF and LAM plus ADV groups at week 48 (4% vs 0%, P = 0.481). There
      were no drug-related adverse effects at week 48 in either group. CONCLUSION:
      Switching to TDF monotherapy was superior to continuous add-on therapy in
      patients with LAM-resistant CHB with a suboptimal response to LAM plus ADV.

PMID- 25759546
TI  - Radical gastrectomy with hepatoarterial catheter implantation for late-stage
      gastric cancer.
AB  - AIM: To determine the optimal type of surgery for late-stage gastric cancer with
      hepatic metastases. METHODS: We retrospectively analyzed 49 gastrectomies for
      late-stage gastric cancer conducted in the First Hospital Affiliated to Henan
      University of Science and Technology between September 2003 and September 2010.
      All gastrectomy operations were divided into two groups: radical resection
      (gastrectomy and simultaneous resection of hepatic metastases, n = 31), and
      palliative resection (gastrectomy without hepatic resection, n = 18). All 49
      patients had chemotherapy catheter implantation in the hepatic artery via the
      gastroduodenal artery. Postoperative complications and cumulative survival rates
      of the two groups were compared and analyzed. RESULTS: There was no significant
      difference in the number of perioperative complications between the radical and
      palliative resection groups (6 and 3 cases, respectively, P > 0.05). The
      incidence of long-term complications including ileus (3 in the radical resection
      and 2 in the palliative resection groups) and anastomosis (2 cases in each group)
      was not significantly different (P > 0.05). The cumulative survival rate was
      significantly lower in the palliative resection group (P < 0.05). CONCLUSION:
      Radical gastrectomy with resection of hepatic metastases and hepatoarterial
      catheter implantation is the recommended surgery for late-stage gastric cancer
      patients with hepatic metastases.

PMID- 25759547
TI  - Fecal microbes, short chain fatty acids, and colorectal cancer across
      racial/ethnic groups.
AB  - AIM: To investigate differences in microbes and short chain fatty acid (SCFA)
      levels in stool samples from Hispanic and non-Hispanic African American, American
      Indian, and White participants. METHODS: Stool samples from twenty participants
      were subjected to analysis for relative levels of viable bacteria and for SCFA
      levels. Additionally, the samples were subjected to 16S rRNA gene pyrosequencing
      for identification of bacteria present in the stool. We used a metagenome
      functional prediction technique to analyze genome copy numbers and estimate the
      abundance of butyrate kinase in all samples. RESULTS: We found that African
      Americans had significantly lower levels of acetate, butyrate, and total SCFAs
      than all other racial/ethnic groups. We also found that participant microbial
      profiles differed by racial/ethnic group. African Americans had significantly
      more Firmicutes than Whites, with enriched Ruminococcaceae. The
      Firmicutes/Bacteroidetes ratio was also significantly higher for African
      Americans than for Whites (P = 0.049). We found Clostridium levels to be
      significantly and inversely related to total SCFA levels (P = 0.019) and we found
      Bacteroides to be positively associated (P = 0.027) and Clostridium to be
      negatively associated (P = 0.012) with levels of butyrate. We also identified a
      correlation between copy number for a butyrate kinase predicted from 16S rRNA
      gene abundance and levels of butyrate in stool. CONCLUSION: The identified
      differences in gut flora and SCFA levels may relate to colorectal cancer
      mortality differentials and may be useful as targets for future clinical and
      behavioral interventions.

PMID- 25759548
TI  - CDX2 protein expression compared to alcian blue staining in the evaluation of
      esophageal intestinal metaplasia.
AB  - AIM: To compare the sensitivity and specificity of CDX2 and alcian blue (AB) pH
      2.5 staining in identifying esophageal intestinal metaplasia. METHODS: One
      hundred and ninty-nine biopsies from 186 patients were retrospectively reviewed
      and categorized as Barrett's esophagus (BE) (n = 108); non-Barrett's esophagus
      (NBE) (n = 48); columnar blue cells (CB) and esophageal glands (EG) (n = 43). The
      biopsies were stained with AB and immunostained for CDX2 using a mouse monoclonal
      antibody from Biogenex (clone CDX2-88) and the Ventana Discovery X automated
      immunostainer. The positive and negative predictive value of each group was used
      to determine the predictive power of CDX2 and AB in diagnosing intestinal
      metaplasia. RESULTS: All of the 108 BE biopsies (100%) were positive for AB and
      102 of them (94.4%) were positive for CDX2. The six BE patients (5.6%) who failed
      to stain with CDX2 were found to have lost the focus of intestinal metaplasia
      upon deeper sectioning for immunostaining. Both AB and CDX2 were negative in 43
      out of 48 (89.6%) NBE cases. Five NBE patients (10.4%) were falsely positive for
      AB due to the presence of EG and CB in these biopsies. These cases were all CDX2
      negative. In addition, 5 AB negative NBE were found to be CDX2 positive. Based on
      these results the CDX2 immunostain had similar sensitivity but higher specificity
      (100% vs about 91%) than AB in detecting intestinal type metaplasia in these
      samples. Our data shows that CDX2 has a better PPV in detecting intestinal
      metaplasia as compared to AB (95.6% vs 71.5%, respectively). CONCLUSION: CDX2 has
      a better positive predictive value than AB in detecting intestinal metaplasia.
      CDX2 may be useful when challenged by gastro-esophageal biopsies containing
      mimikers of BE.

PMID- 25759549
TI  - Prolonged overall survival in gastric cancer patients after adoptive
      immunotherapy.
AB  - AIM: To assess the efficacy of immunotherapy with expanded activated autologous
      lymphocytes (EAALs) in gastric cancer. METHODS: An observational study was
      designed to retrospectively analyze the clinical data of 84 gastric cancer
      patients, of whom 42 were treated by EAAL immunotherapy plus conventional
      treatment and another 42 only received conventional treatment (control group).
      EAALs were obtained by proliferation of peripheral blood mononuclear cells from
      patients followed by phenotype determination. Clinical data including age,
      gender, clinical stage, chemotherapeutic regimens, hospitalization, surgical,
      radiotherapy, and survival data were collected along with EAAL therapy details
      and side effects. Patients were followed and the relationship between treatment
      and overall survival (OS) data obtained for the immunotherapy and control groups
      were compared retrospectively. The safety of EAAL immunotherapy was also
      evaluated. RESULTS: After in vitro culture and proliferation, the percentages of
      CD3+, CD3+CD8+, CD8+CD27+, CD8+CD28+, and CD3+CD16+/CD56+ cells increased
      remarkably (P < 0.05), while the percentages of CD3+CD4+, CD4+CD25+, and CD3
      CD16+/CD56+ (natural killer cells) were overtly decreased (P < 0.05); no
      significant change was observed in CD4+CD25+CD127- cells (P = 0.448).
      Interestingly, OS in the immunotherapy group was significantly higher than that
      in the control group, with 27.0 and 13.9 mo obtained for the two groups,
      respectively (P = 0.028, HR = 0.573, 95%CI: 0.347-0.945). These findings
      indicated a 42.7% decrease in the risk of death. In addition, we found that
      clinical stage and application of EAAL immunotherapy were independent prognostic
      factors for gastric cancer patients. Indeed, the OS in stage IIIc and IV patients
      that had received surgery was prolonged after EAAL immunotherapy (P < 0.05).
      Importantly, in vitro induction and proliferation of EAAL were easy and
      biologically safe. CONCLUSION: Overall, EAAL adoptive immunotherapy might prolong
      the OS in gastric cancer patients.

PMID- 25759550
TI  - Primary antibiotic resistance of Helicobacter pylori strains isolated from
      patients with dyspeptic symptoms in Beijing: a prospective serial study.
AB  - AIM: To determine the resistance patterns of Helicobacter pylori (H. pylori)
      strains isolated from patients in Beijing and monitor the change of antibiotic
      resistance over time. METHODS: In this prospective, serial and cross-sectional
      study, H. pylori cultures were successfully obtained from 371 and 950 patients
      (never receiving eradication) during 2009-2010 and 2013-2014, respectively.
      Resistance to amoxicillin, clarithromycin, metronidazole, levofloxacin,
      tetracycline, and rifampicin was determined by Epsilometer test. RESULTS: The
      resistance rates of isolates obtained during 2009-2010 were 66.8%, 39.9%, 34.5%,
      15.4%, 6.7%, and 4.9% to metronidazole, clarithromycin, levofloxacin, rifampicin,
      amoxicillin and tetracycline, respectively; and the corresponding rates for
      isolates during 2013-2014 were 63.4%, 52.6%, 54.8%, 18.2%, 4.4% and 7.3%,
      respectively. The resistance rates to clarithromycin and levofloxacin were
      significantly increased after four years. In 2009-2010, 14.6% of H. pylori
      isolates were susceptible to all tested antibiotics, with mono (33.7%), double
      (28.3%), triple (16.7%), quadruple (6.2%), quintuple (0.3%) and sextuple
      resistance (0.3%) also being detected. In 2013-2014, 9.4% were susceptible to all
      tested antibiotics, and mono (27.6%), double (28.4%), triple (24.9%), quadruple
      (7.3%), quintuple (2.3%) and sextuple resistance (0.1%) was also observed. More
      multiple resistant H. pylori isolates were found during 2013-2014. Gender (to
      levofloxacin and metronidazole), age (to levofloxacin) and endoscopic findings
      (to clarithromycin) were independent factors influencing antibiotic resistance.
      CONCLUSION: H. pylori resistance to commonly used antibiotics in Beijing is high
      with increased multiple antibiotic resistance.

PMID- 25759551
TI  - Tolerability of magnifying narrow band imaging endoscopy for esophageal cancer
      screening.
AB  - AIM: To compare the tolerability of magnifying narrow band imaging endoscopy for
      esophageal cancer screening with that of lugol chromoendoscopy. METHODS: We
      prospectively enrolled and analyzed 51 patients who were at high risk for
      esophageal cancer. All patients were divided into two groups: a magnifying narrow
      band imaging group, and a lugol chromoendoscopy group, for comparison of adverse
      symptoms. Esophageal cancer screening was performed on withdrawal of the
      endoscope. The primary endpoint was a score on a visual analogue scale for
      heartburn after the examination. The secondary endpoints were scale scores for
      retrosternal pain and dyspnea after the examinations, change in vital signs,
      total procedure time, and esophageal observation time. RESULTS: The scores for
      heartburn and retrosternal pain in the magnifying narrow band imaging group were
      significantly better than those in the lugol chromoendoscopy group (P = 0.004,
      0.024, respectively, ANOVA for repeated measures). The increase in heart rate
      after the procedure was significantly greater in the lugol chromoendoscopy group.
      There was no significant difference between the two groups with respect to other
      vital sign. The total procedure time and esophageal observation time in the
      magnifying narrow band imaging group were significantly shorter than those in the
      lugol chromoendoscopy group (450 +/- 116 vs 565 +/- 174, P = 0.004, 44 +/- 26 vs
      151 +/- 72, P < 0.001, respectively). CONCLUSION: Magnifying narrow band imaging
      endoscopy reduced the adverse symptoms compared with lugol chromoendoscopy.
      Narrow band imaging endoscopy is useful and suitable for esophageal cancer
      screening periodically.

PMID- 25759552
TI  - Effect of intravariceal sclerotherapy combined with esophageal mucosal
      sclerotherapy using small-volume sclerosant for cirrhotic patients with high
      variceal pressure.
AB  - AIM: To explore the effect of intravariceal-mucosal sclerotherapy using small
      dose of sclerosant on the recurrence of esophageal varices. METHODS: We randomly
      assigned 38 cirrhotic patients with previous variceal bleeding and high variceal
      pressure (> 15.2 mmHg) to receive endoscopic variceal ligation (EVL) and combined
      intravariceal and esophageal mucosal sclerotherapy (combined group) using small
      volume sclerosant. The end-points of the study were rebleeding and recurrence of
      esophageal varices. RESULTS: During a median follow-up period of 16 mo, varices
      recurred in 1 patient in the combined group as compared with 7 patients in the
      EVL group (P = 0.045). Rebleeding occurred in 3 patients in the EVL group as
      compared with 1 patient in the combined group (P = 0.687). No patient died in the
      two groups. No significant differences were observed between the two groups with
      respect to serious adverse events. CONCLUSION: Intravariceal-mucosal
      sclerotherapy using small dose of sclerosant is more effective than EVL in
      decreasing the incidence of variceal recurrence for cirrhotic patients.

PMID- 25759553
TI  - Prognostic significance of neutrophil to lymphocyte ratio in pancreatic cancer: a
      meta-analysis.
AB  - AIM: To conduct a meta-analysis evaluating the association between the peripheral
      blood neutrophil to lymphocyte ratio (NLR) and the outcome of patients with
      pancreatic cancer. METHODS: Studies evaluating the relationship between the
      peripheral blood NLR and outcome of patients with pancreatic cancer published up
      to May 2014 were searched using electronic databases, including PubMed, Web of
      Science, Embase and Ovid. A meta-analysis was performed to pool the hazard ratios
      (HRs) or odds ratios (ORs) and their 95% confidence intervals (CIs) using either
      a fixed-effects model or a random-effects model to quantitatively assess the
      prognostic value of NLR and its association with clinicopathological parameters.
      RESULTS: Eleven studies containing a total of 1804 patients were eligible
      according to our selection criteria, and combined hazard ratios indicated that
      high NLR was a poor prognostic marker for pancreatic cancer patients because it
      had an unfavorable impact on the overall survival (OS) (HR = 2.61, 95%CI: 1.68
      4.06, P = 0.000) and cancer specific survival (HR = 1.66, 95%CI: 1.08-2.57, P =
      0.021). Subgroup analysis revealed that high NLR was associated with poor OS in
      patients with mixed treatment (HR = 4.36, 95%CI: 2.50-7.61, P = 0.000),
      chemotherapy (HR = 2.08, 95%CI: 1.49-2.9, P = 0.000), or surgical resection (HR =
      1.2, 95%CI: 1.00-1.44, P = 0.048). Additionally, high NLR was significantly
      correlated with tumor metastasis (OR = 1.69, 95%CI: 1.10-2.59, P = 0.016), poor
      tumor differentiation (OR = 2.75, 95%CI: 1.19-6.36, P = 0.016), poor performance
      status (OR = 2.56, 95%CI: 1.63-4.03, P = 0.000), high cancer antigen 199 (OR =
      2.62, 95%CI: 1.49-4.60, P = 0.000), high C-reactive protein (OR = 4.32, 95%CI:
      2.71-6.87, P = 0.000), and low albumin (OR = 3.56, 95%CI: 1.37-9.27, P = 0.009).
      CONCLUSION: High peripheral blood NLR suggested a poor prognosis for patients
      with pancreatic cancer, and it could be a novel marker of survival evaluation and
      could help clinicians develop therapeutic strategies for pancreatic cancer
      patients.

PMID- 25759554
TI  - N-acetylcysteine treats intravenous amiodarone induced liver injury.
AB  - We report a case of intravenous (IV) amiodarone drug induced liver injury (DILI).
      The patient received IV N-acetylcysteine (NAC) which resulted in a rapid
      improvement in liver enzymes. While the specific mechanisms for the pathogenesis
      of IV amiodarone DILI and the therapeutic action of IV NAC are both unknown, this
      case strongly implies at least some commonality. Because IV amiodarone is
      indicated for the treatment of serious cardiac arrhythmias in an intensive care
      unit setting, some degree of ischemic hepatitis is likely a cofactor in most
      cases. 

PMID- 25759555
TI  - Pancreatic intraductal papillary mucinous neoplasm in a patient with Lynch
      syndrome.
AB  - Intraductal papillary mucinous neoplasm (IPMN) is a mucin-producing epithelial
      neoplasm that carries a risk of progression to invasive pancreatic ductal
      adenocarcinoma. Lynch syndrome is an autosomal dominant condition caused by
      germline mutations in mismatch repair genes such as MSH2 that lead to
      microsatellite instability and increased risk of tumor formation. Although
      families with Lynch syndrome have an increased risk of pancreatic cancer, a clear
      connection between Lynch syndrome and IPMN has not been drawn. We present a
      report of a 58 year-old Caucasian woman with multiple cancers and a germline
      mutation of MSH2 consistent with Lynch syndrome. A screening abdominal computed
      tomography scan revealed a dilated main pancreatic duct and cystic ductular
      structure in the uncinate process that were consistent with IPMN of the main
      pancreatic duct on excision. Immunohistochemistry and polymerase chain reaction
      of the patient's pancreas specimen did not reveal microsatellite instability or
      mismatch repair gene loss of expression or function. Our findings may be
      explained by the fact that loss of mismatch repair function and microsatellite
      instability is a late event in neoplastic transformation. Given the relative
      rarity of main duct IPMN, its appearance in the setting of somatic MSH2 mutation
      suggests that IPMN may fit into the constellation of Lynch syndrome related
      malignancies.

PMID- 25759556
TI  - Protracted anaphylaxis developed after peginterferon alpha-2a administration for
      chronic hepatitis C.
AB  - Peginterferon is a key drug used to treat chronic viral hepatitis that is known
      for causing various side effects. Side effects occurring immediately after
      administration include headache, nausea, and influenza-like symptoms, such as
      fever and joint pain. However, reports of anaphylactic shock are extremely rare.
      Here we report a patient with protracted anaphylaxis who suffered shock symptoms
      after peginterferon alpha-2a administration for chronic hepatitis C. Although the
      patient improved temporarily with shock treatment, symptoms of anaphylaxis
      recurred. As peginterferon is often administered on an outpatient basis, it is
      important to recognize life-threatening side effects that may develop in a
      protracted manner. 

PMID- 25759557
TI  - Postsurgical radiation therapy for gastric carcinosarcoma with c-kit expression:
      a case report.
AB  - Gastric carcinosarcomas are rare morphologically biphasic tumors, consisting of
      carcinoma and sarcoma components, with a poor clinical course. Here we report the
      case of a 70-year-old man with advanced Borrmann type III carcinosarcoma arising
      from the upper body of the stomach with extensive lymph node metastasis who
      underwent a total, but palliative, gastrectomy. Histology showed the tumor
      consisted of a biphasic structure of tubular adenocarcinoma and spindle cell
      sarcoma. Immunohistochemistry revealed sarcoma cells expressing c-kit (CD117) and
      CD34, which are criteria for gastrointestinal stromal tumors. Nine months after
      the surgical operation, tumor metastases had extended to the hepatohilar,
      retroperitoneal and mediastinal lymph nodes. Radiation therapy of 50 Gy markedly
      decreased the size of each of these nodes and reduced the risk of respiratory
      complications and jaundice. However, the patient died of respiratory failure due
      to bronchopneumonia with multiple lung metastases 22 mo after resection. Autopsy
      revealed severe necrosis in most of the lymph nodes with tumor metastases.
      Radiation therapy combined with gastrectomy should be considered to improve
      survival in patients with gastric carcinosarcomas that express c-kit. 

PMID- 25759558
TI  - Non-surgical contraindication for acute appendicitis with secondary
      thrombocytopenia: a case report.
AB  - A 26-year-old man presented with migrated right lower abdominal pain and without
      any history of hematological systemic diseases. Blood routine test showed a
      leukocyte count of 22.74 * 10(9)/L, with 91.4% neutrophils, and a platelet count
      of 4 * 10(9)/L before admission. The case question was whether the team should
      proceed with surgery. Obviously, a differential diagnosis is essential before
      making such a decision. Acute appendicitis was easily diagnosed based on clinical
      findings, including migrating abdominal pain, a leukocyte count of 22.74 *
      10(9)/L and the result of abdominal computed tomography scan. However, it was not
      clear whether the severe thrombocytopenia was primary or secondary. So smear of
      peripheral blood and aspiration of bone marrow were ordered to exclude
      hematological diseases. Neither of the tests indicated obvious pathological
      hematological changes. There was no hepatosplenomegaly found by ultrasound
      examination of the liver and spleen. Therefore, operative intervention may be a
      unique clinical scenario in acute severe appendicitis patients with secondary
      thrombocytopenia. 

PMID- 25759559
TI  - Retrospective observation of therapeutic effects of adult auxiliary partial
      living donor liver transplantation on postpartum acute liver failure: a case
      report.
AB  - We present a female patient with preterm labor, severe viral hepatitis B of acute
      phase, hepatic encephalopathy stage III and coma. After delivery, the illness was
      exacerbated and the patient presented with clinical signs of vital organ
      dysfunctions such as acute respiratory distress syndrome, cerebral edema and
      hypoxemia that needed mechanical ventilation. Emergency liver transplantation was
      recommended after multidisciplinary panel consultations. The donor, her mother,
      consented to donate her right liver. Auxiliary partial orthotopic living donor
      liver transplantion (APOLDLT) was performed. After operation, the patient was on
      triple medication of tacrolimus plus mofetil mycophenolate and prednisone for
      immunosuppression. The combination of anti-hepatitis B virus (HBV) immunoglobulin
      and entecavir was initiated for anti-HBV therapy. Both the patient and the donor
      recovered well without any complications. The patient was followed up regularly.
      Her liver function, clinical signs and symptoms improved significantly. Until
      now, the recipient has been living for more than 78 mo free of any complications.
      The APOLDLT is a life-saving modality for rescuing patients with high-risk acute
      liver failure following HBV infection without available donor and hence is
      recommended under standardized antiviral therapy coverage as stated above.

PMID- 25759560
TI  - Robot-assisted one-stage resection of rectal cancer with liver and lung
      metastases.
AB  - The Da Vinci Surgical System may help to overcome some of the difficulties of
      laparoscopy for complicated abdominal surgery. The authors of this article
      present a case of robot-assisted, one-stage radical resection of three tumors,
      including robotic anterior resection for rectal cancer, segmental hepatectomy for
      liver metastasis, and wedge-shaped excision for lung metastasis. A 59-year-old
      man with primary rectal cancer and liver and lung metastases was operated upon
      with a one-stage radical resection approach using the Da Vinci Surgical System.
      Resection and anastomosis of rectal cancer were performed extracorporeally after
      undocking the robot. The procedure was successfully completed in 500 min. No
      surgical complications occurred during the intervention and postoperative period,
      and no conversion to laparotomy or additional trocars were required. To the best
      of our knowledge, this is the first case of simultaneous resection for rectal
      cancer with liver and lung metastases using the Da Vinci Surgery System to be
      reported. The procedure is feasible and safe and its main advantages for patient
      are avoiding repeated operation, reducing surgical trauma, shortening recovery
      time, and early implementation of postoperative adjuvant therapy.

PMID- 25759561
TI  - Common bile duct injury by fibrin glue: report of a rare complication.
AB  - Fibrin glue is widely used in clinical practice and plays an important role in
      reducing postoperative complications. We report a case of a 65-year-old man,
      whose common bile duct was injured by fibrin glue, with a history of failed
      laparoscopic cholecystectomy and open operation for uncontrolled laparoscopic
      bleeding. In view of the persistent liver dysfunction, xanthochromia and skin
      itching, the patient was admitted to us for further management. Ultrasound,
      computed tomography, and magnetic resonance cholangiopancreatography (MRCP)
      revealed multiple stones in the common bile duct, and liver function tests
      confirmed the presence of obstructive jaundice and liver damage. Endoscopic
      retrograde cholangiopancreatography was unsuccessfully performed to remove
      choledocholithiasis, but a small amount of tissue was removed and pathologically
      confirmed as calcified biliary mucosa. This was followed by open surgery for
      suspicious cholangiocarcinoma. There was no evidence of cholangiocarcinoma, but
      the common bile duct wall had a defect of 8 mm * 10 mm at Calot's triangle. A
      hard, grid-like foreign body was removed, which proved to be solid fibrin glue.
      Subsequently, the residual choledocholithiasis was removed by a choledochoscopic
      procedure, and the common bile duct deletion was repaired by liver round ligament
      with T-tube drainage. Six months later, endoscopy was performed through the T
      tube fistula and showed a well-repaired bile duct wall. Eight months later, MRCP
      confirmed no bile duct stenosis. A review of reported cases showed that fibrin
      glue is widely used in surgery, but it can also cause organ damage. Its mechanism
      may be related to discharge reactions. 

PMID- 25759562
TI  - Portal vein aneurysm associated with Budd-Chiari syndrome treated with
      transjugular intrahepatic portosystemic shunt: a case report.
AB  - A 65-year-old woman with Budd-Chiari syndrome (BCS) presented with right upper
      quadrant pain. A computed tomography (CT) scan showed a saccular aneurysm located
      at the extrahepatic portal vein main branch measuring 3.2 cm in height and 2.5 cm
      * 2.4 cm in diameter. The aneurysm was thought to be associated with BCS as there
      was no preceding history of trauma and it had not been present on Doppler
      ultrasound examination performed 3 years previously. Because of increasing pain
      and concern for complications due to aneurysm size, the decision was made to
      relieve the hepatic venous outflow obstruction. Transjugular intrahepatic
      portosystemic shunt (TIPS) was created without complications. She had complete
      resolution of her abdominal pain within 2 d and remained asymptomatic after 1
      year of follow-up. CT scans obtained after TIPS showed that the aneurysm had
      decreased in size to 2.4 cm in height and 2.0 cm * 1.9 cm in diameter at 3 mo,
      and had further decreased to 1.9 cm in height and 1.6 cm * 1.5 cm in diameter at
      1 year. 

PMID- 25759563
TI  - Perforation of small bowel caused by Schistosoma japonicum: a case report.
AB  - A 67-year-old man from Jingzhou was admitted to the First Hospital Affiliated to
      Yangtze University in July 2013 with sudden onset of abdominal pain with
      dizziness for 12 h. The patient had sign of peritoneal irritation.
      Ultrasonography of the abdomen and pelvis showed hepatic fibrosis due to
      schistosomiasis. Computed tomography showed free gas in the peritoneal cavity.
      Plain abdominal radiography showed bilateral subdiaphragmatic accumulation of
      gas, perforation of the viscus, and radio-opacity in the left renal area. The
      patient underwent emergency exploratory laparotomy. At laparotomy, a moderate
      amount of muddy yellow pus was found in the intra-abdominal cavity. At the
      junction of the jejunum and ileum, about 250 cm from Treitz's ligament, there was
      an about 10-cm length of inflamed small bowel with perforation (3 mm in diameter)
      along the mesenteric border at the middle of the lesion. The patient underwent
      resection of the affected intestinal segment, along with end-to-end intestinal
      anastomosis. Histopathological examination revealed mucosal necrosis and
      hemorrhage with a large number of infiltrating eosinophils and neutrophils, and
      acute submucosal inflammation with a large number of infiltrating eosinophils and
      neutrophils associated with Schistosoma japonicum (S. japonicum) eggs. No
      intravascular adult parasite was found. Postoperatively, the patient was treated
      with praziquantel (30 mg/kg daily) for 4 d. The patient progressed well. To the
      best of our knowledge, this is the first case of small bowel perforation
      associated with eggs of S. japonicum. 

PMID- 25759564
TI  - Koenimbin, a natural dietary compound of Murraya koenigii (L) Spreng: inhibition
      of MCF7 breast cancer cells and targeting of derived MCF7 breast cancer stem
      cells (CD44(+)/CD24(-/low)): an in vitro study.
AB  - BACKGROUND: Inhibition of breast cancer stem cells has been shown to be an
      effective therapeutic strategy for cancer prevention. The aims of this work were
      to evaluate the efficacy of koenimbin, isolated from Murraya koenigii (L) Spreng,
      in the inhibition of MCF7 breast cancer cells and to target MCF7 breast cancer
      stem cells through apoptosis in vitro. METHODS: Koenimbin-induced cell viability
      was evaluated using the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium
      bromide) assay. Nuclear condensation, cell permeability, mitochondrial membrane
      potential, and cytochrome c release were observed using high-content screening.
      Cell cycle arrest was examined using flow cytometry, while human apoptosis
      proteome profiler assays were used to investigate the mechanism of apoptosis.
      Protein expression levels of Bax, Bcl2, and heat shock protein 70 were confirmed
      using Western blotting. Caspase-7, caspase-8, and caspase-9 levels were measured,
      and nuclear factor kappa B (NF-kappaB) activity was assessed using a high-content
      screening assay. AldefluorTM and mammosphere formation assays were used to
      evaluate the effect of koenimbin on MCF7 breast cancer stem cells in vitro. The
      Wnt/beta-catenin signaling pathway was investigated using Western blotting.
      RESULTS: Koenimbin-induced apoptosis in MCF7 cells was mediated by cell death
      transducing signals regulating the mitochondrial membrane potential by
      downregulating Bcl2 and upregulating Bax, due to cytochrome c release from the
      mitochondria to the cytosol. Koenimbin induced significant (P<0.05) sub-G0 phase
      arrest in breast cancer cells. Cytochrome c release triggered caspase-9
      activation, which then activated caspase-7, leading to apoptotic changes. This
      form of apoptosis is closely associated with the intrinsic pathway and inhibition
      of NF-kappaB translocation from the cytoplasm to the nucleus. Koenimbin
      significantly (P<0.05) decreased the aldehyde dehydrogenase-positive cell
      population in MCF7 cancer stem cells and significantly (P<0.01) decreased the
      size and number of MCF7 cancer stem cells in primary, secondary, and tertiary
      mammospheres in vitro. Koenimbin also significantly (P<0.05) downregulated the
      Wnt/beta-catenin self-renewal pathway. CONCLUSION: Koenimbin has potential for
      future chemoprevention studies, and may lead to the discovery of further cancer
      management strategies by reducing cancer resistance and recurrence and improving
      patient survival.

PMID- 25759565
TI  - Pharmacokinetic interaction between udenafil and dapoxetine: a randomized, open
      labeled crossover study in healthy male volunteers.
AB  - BACKGROUND: "Udenafil" is a phosphodiesterase-5 inhibitor indicated for erectile
      dysfunction. "Dapoxetine" is a serotonin transport inhibitor indicated for
      premature ejaculation. The aim of the study reported here was to investigate the
      pharmacokinetic drug interaction between udenafil and dapoxetine in healthy male
      subjects. METHODS: An open-label, three-treatment, six-sequence, three-period
      crossover study was performed in healthy male subjects. In varying sequences,
      each subjects received single oral doses of udenafil 200 mg, dapoxetine 60 mg,
      and both treatments. The periods were separated by a washout period of 7 days.
      Serial blood samples were collected up to 48 hours after dosing. The plasma
      concentrations of udenafil and dapoxetine were determined using a validated
      liquid chromatography-tandem mass spectrometry method. Pharmacokinetic parameters
      were obtained by non-compartmental analysis. Tolerability was assessed throughout
      the study. RESULTS: Twenty-three healthy subjects completed the study. The
      geometric mean ratios of the area under the plasma concentration-time curve from
      time 0 to last measurable time point and measured peak plasma concentration for
      udenafil were 0.923 (90% confidence interval [CI]: 0.863-0.987) and 0.864 (90%
      CI: 0.789-0.947), respectively. The geometric mean ratios of the area under the
      plasma concentration-time curve from time 0 to last measurable time point and
      measured peak plasma concentration for dapoxetine were 1.125 (90% CI: 1.044
      1.213) and 0.837 (90% CI: 0.758-0.925), respectively. There were no serious
      adverse events reported, and none of the subjects dropped out due to adverse
      events. CONCLUSION: Udenafil was found to have no clinically significant
      pharmacokinetic interactions with dapoxetine. The concurrent administration of
      udenafil and dapoxetine was generally well tolerated.

PMID- 25759566
TI  - Advantageous effects of immunosuppression with tacrolimus in comparison with
      cyclosporine A regarding renal function in patients after heart transplantation.
AB  - BACKGROUND: Nephrotoxicity is a serious adverse effect of calcineurin inhibitor
      therapy in patients after heart transplantation (HTX). AIM: In this retrospective
      registry study, renal function within the first 2 years after HTX in patients
      receiving de novo calcineurin inhibitor treatment, that is, cyclosporine A (CSA)
      or tacrolimus (TAC), was analyzed. In a consecutive subgroup analysis, renal
      function in patients receiving conventional tacrolimus (CTAC) was compared with
      that of patients receiving extended-release tacrolimus (ETAC). METHODS: Data from
      150 HTX patients at Heidelberg Heart Transplantation Center were retrospectively
      analyzed. All patients were continuously receiving the primarily applied
      calcineurin inhibitor during the first 2 years after HTX and received follow-up
      care according to center practice. RESULTS: Within the first 2 years after HTX,
      serum creatinine increased significantly in patients receiving CSA (P<0.0001),
      whereas in patients receiving TAC, change of serum creatinine was not
      statistically significant (P=not statistically significant [ns]). McNemar's test
      detected a significant accumulation of patients with deterioration of renal
      function in the first half year after HTX among patients receiving CSA
      (P=0.0004). In patients receiving TAC, no significant accumulation of patients
      with deterioration of renal function during the first 2 years after HTX was
      detectable (all P=ns). Direct comparison of patients receiving CTAC versus those
      receiving ETAC detected no significant differences regarding renal function
      between patients primarily receiving CTAC or ETAC treatment during study period
      (all P=ns). CONCLUSION: CSA is associated with a more pronounced deterioration of
      renal function, especially in the first 6 months after HTX, in comparison with
      patients receiving TAC as baseline immunosuppressive therapy.

PMID- 25759567
TI  - Extent and reasons for nonadherence to antihypertensive, cholesterol, and
      diabetes medications: the association with depressive symptom burden in a sample
      of American veterans.
AB  - OBJECTIVE: Persons with depressive symptoms generally have higher rates of
      medication nonadherence than persons without depressive symptoms. However, little
      is known about whether this association differs by comorbid medical condition or
      whether reasons for nonadherence differ by depressive symptoms or comorbid
      medical condition. METHODS: Self-reported extent of nonadherence, reasons for
      nonadherence, and depressive symptoms among 1,026 veterans prescribed medications
      for hypertension, dyslipidemia, and/or type 2 diabetes were assessed. RESULTS: In
      multivariable logistic regression adjusted for clinical and demographic factors,
      the odds of nonadherence were higher among participants with high depressive
      symptom burden for dyslipidemia (n=848; odds ratio [OR]: 1.42, P=0.03) but not
      hypertension (n=916; OR: 1.24, P=0.15), or type 2 diabetes (n=447; OR: 1.15,
      P=0.51). Among participants reporting nonadherence to antihypertensive and
      antilipemic medications, those with greater depressive symptom burden had greater
      odds of endorsing medication nonadherence reasons related to negative
      expectations and excessive economic burden. Neither extent of nonadherence nor
      reasons for nonadherence differed by depressive symptom burden among patients
      with diabetes. CONCLUSION: These findings suggest that clinicians may consider
      tailoring interventions to improve adherence to antihypertensive and antilipemic
      medications to specific medication concerns of participants with depressive
      symptoms.

PMID- 25759568
TI  - Inertial sensors as measurement tools of elbow range of motion in gerontology.
AB  - BACKGROUND AND PURPOSE: Musculoskeletal system deterioration among the aging is a
      major reason for loss of autonomy and directly affects the quality of life of the
      elderly. Articular evaluation is part of physiotherapeutic assessment and helps
      in establishing a precise diagnosis and deciding appropriate therapy. Reference
      instruments are valid but not easy to use for some joints. The main goal of our
      study was to determine reliability and intertester reproducibility of the MP-BV,
      an inertial sensor (the MotionPod((r)) [MP]) combined with specific software
      (BioVal [BV]), for elbow passive range-of-motion measurements in geriatrics.
      METHODS: This open, monocentric, randomized study compared inertial sensor to
      inclinometer in patients hospitalized in an acute, post-acute, and long-term-care
      gerontology unit. RESULTS: Seventy-seven patients (mean age 83.5+/-6.4 years, sex
      ratio 1.08 [male/female]) were analyzed. The MP-BV was reliable for each of the
      three measurements (flexion, pronation, and supination) for 24.3% (CI 95% 13.9
      32.8) of the patients. Separately, the percentages of reliable measures were
      59.7% (49.2-70.5) for flexion, 68.8% (58.4-79.5) for pronation, and 62.3% (51.2
      73.1) for supination. The intraclass correlation coefficients were 0.15 (0.07
      0.73), 0.46 (0.27-0.98), and 0.50 (0.31-40 0.98) for flexion, pronation, and
      supination, respectively. CONCLUSION: This study shows the convenience of the MP
      BV in terms of ease of use and of export of measured data. However, this
      instrument seems less reliable and valuable compared to the reference instruments
      used to measure elbow range of motion in gerontology.

PMID- 25759569
TI  - Association between muscle mass and adipo-metabolic profile: a cross-sectional
      study in older subjects.
AB  - BACKGROUND: Sarcopenia, the decrease in muscle mass and function, may lead to
      various negative health outcomes in elderly. The association among sarcopenia
      with adiposity and metabolic markers has rarely been studied in the elderly
      population, with controversial results. The aim of this study is to evaluate this
      relationship in older subjects. METHODS: A cross-sectional study was conducted in
      290 elderly patients, focusing on the possible association between muscle mass
      loss, assessed by relative skeletal muscle mass (RSMM), and an adipo-metabolic
      profile (AMP) defined by adiposity and metabolic biochemical markers.
      Measurements of body composition were assessed by dual energy X-ray
      absorptiometry. Biochemical parameters, such as albumin, low-density lipoprotein
      cholesterol, high-density lipoprotein cholesterol, total cholesterol,
      triglycerides, C-reactive protein, and homocysteine and its related markers
      (folate and vitamin B12) were measured. Using canonical correlation analysis and
      structural equation modeling, an individual score of AMP was created and
      correlated with RSMM. RESULTS: The AMP-RSMM correlation was equal to +0.642 (95%
      confidence interval, +0.512 to +0.773; P<0.001). Hence, a negative association
      between sarcopenia severity and adiposity/metabolic biochemical markers was
      highlighted. CONCLUSION: This study contained a novel way to examine the
      relationship between the variables of interest based on a composite index of
      adiposity and metabolic conditions. Results shed light on the orientation and
      magnitude of adiposity and metabolic markers in preventing muscle mass loss.
      There might be a protective effect of adiposity, compatible with the "obesity
      paradox."

PMID- 25759570
TI  - Kinematic analysis of motor strategies in frail aged adults during the Timed Up
      and Go: how to spot the motor frailty?
AB  - OBJECTIVE: The purpose of this work was to analyze and compare the movement
      kinematics of sit-to-stand (STS) and back-to-sit (BTS) transfers between frail
      aged adults and young subjects, as well as to determine the relationship between
      kinematic changes and functional capacities. METHODS: We analyzed the Timed Up
      and Go (TUG) movements by using a 3D movement analysis system for real-time
      balance assessment in frail elderly. Ten frail aged adults (frail group [FG]) and
      ten young subjects (young group [YG]) performed the TUG. Seven spatiotemporal
      parameters were extracted and compared between the two groups. Moreover, these
      parameters were plotted with TUG test duration. RESULTS: The experiments revealed
      that there were significant differences between FG and YG in trunk angle during
      both STS and BTS, and in TUG duration. The trunk angle of the young subjects was
      more than two times higher than that of the FG. As expected, the TUG duration was
      higher in the FG than in YG. Trunk angles during both transfers were the most
      different parameters between the groups. However, the BTS trunk angle and STS
      ratio were more linked to functional capacities. CONCLUSION: There was a
      relationship between kinematic changes, representing the motor planning
      strategies, and physical frailty in these aged adults. These changes should be
      taken into account in clinical practice.

PMID- 25759571
TI  - Self-reported sleep quality and acute exacerbations of chronic obstructive
      pulmonary disease.
AB  - BACKGROUND: Many patients with chronic obstructive pulmonary disease (COPD)
      suffer from poor sleep quality. We hypothesized that poor sleep quality in
      otherwise stable patients predicted exacerbations in these patients. METHODS:
      This is a secondary analysis of the results of a previously published randomized
      trial of azithromycin in 1,117 patients with moderate to severe COPD who were
      clinically stable on enrollment. Sleep quality was measured using the Pittsburgh
      Sleep Quality Index. Other quality of life indices included the Medical Outcome
      Study 36-item Short Form Health Survey and the St Georges Respiratory
      Questionnaire. Outcomes included time to first exacerbation and exacerbation
      rate. RESULTS: Sleep quality was "poor" (Pittsburgh Sleep Quality Index >5) in
      53% of participants but was not related to age or severity of airflow
      obstruction. Quality of life scores were worse in "poor" sleepers than in "good"
      sleepers. Major classes of comorbid conditions, including psychiatric,
      neurologic, and musculoskeletal disease, were more prevalent in the "poor"
      sleepers. Unadjusted time to first exacerbation was shorter (190 versus 239 days)
      and exacerbation rate (1.7 versus 1.37 per year) was greater in the poor
      sleepers, but no differences were observed after adjusting for medications and
      comorbid conditions associated with poor sleep. CONCLUSION: Poor sleepers had
      greater exacerbation rates than did good sleepers. This appeared to be due
      largely to them having more, or more severe, concomitant medical conditions and
      taking more medications.

PMID- 25759572
TI  - Exhaled volatile organic compounds discriminate patients with chronic obstructive
      pulmonary disease from healthy subjects.
AB  - Chronic obstructive pulmonary disease (COPD) is a chronic airway inflammatory
      disease characterized by incompletely reversible airway obstruction. This
      clinically heterogeneous group of patients is characterized by different
      phenotypes. Spirometry and clinical parameters, such as severity of dyspnea and
      exacerbation frequency, are used to diagnose and assess the severity of COPD. The
      purpose of this study was to investigate whether volatile organic compounds
      (VOCs) could be detected in the exhaled breath of patients with COPD and whether
      these VOCs could distinguish COPD patients from healthy subjects. Moreover, we
      aimed to investigate whether VOCs could be used as biomarkers for classifying
      patients into different subgroups of the disease. Ion mobility spectrometry was
      used to detect VOCs in the exhaled breath of COPD patients. One hundred and
      thirty-seven peaks were found to have a statistically significant difference
      between the COPD group and the combined healthy smokers and nonsmoker group. Six
      of these VOCs were found to correctly discriminate COPD patients from healthy
      controls with an accuracy of 70%. Only 15 peaks were found to be statistically
      different between healthy smokers and healthy nonsmokers. Furthermore, by
      determining the cutoff levels for each VOC peak, it was possible to classify the
      COPD patients into breathprint subgroups. Forced expiratory volume in 1 second,
      body mass index, and C-reactive protein seem to play a role in the discrepancies
      observed in the different breathprint subgroups. 

PMID- 25759573
TI  - Detection of COPD in a high-risk population: should the diagnostic work-up
      include bronchodilator reversibility testing?
AB  - BACKGROUND: Underdiagnosis of chronic obstructive pulmonary disease (COPD) is
      widespread. Early detection of COPD may improve the outcome by timely smoking
      cessation, a change in lifestyle, and treatment with an inhaled bronchodilator
      (BD). The objective of this study was to evaluate the diagnostic role of BD
      reversibility testing in early COPD case finding. METHODS: General practitioners
      (n=241) consecutively recruited subjects aged >=35 years with relevant exposure
      (history of smoking, and/or occupational exposure) and at least one respiratory
      symptom. Information on age, smoking status, body mass index, dyspnea score
      (Medical Research Council scale), and spirometry was obtained. Individuals with
      airway obstruction (forced expiratory volume in one second [FEV1]/forced vital
      capacity [FVC] <0.70) underwent a BD test with an inhaled beta2 agonist, which
      was considered positive if DeltaFEV1 was >0.20 L and >12%. Asthma and COPD were,
      respectively, defined as an FEV1 increase >0.50 L and a post-BD FEV1/FVC <0.70.
      RESULTS: In total, 4,049 subjects (51% male) were included (mean age 58 years,
      body mass index 27, 32 pack-years of smoking). A significant BD response was
      found in 143 (15%) of the 937 subjects (23%) with airway obstruction at screening
      spirometry. In 59% of these subjects, the post-BD FEV1/FVC remained <0.70. In 24%
      of the subjects with pre-BD airway obstruction, the post-BD FEV1/FVC ratio was
      within the reference range. In subjects with confirmed COPD, the mean increase in
      FEV1 following BD was 0.11 L+/-0.10 L. The subjects with COPD and a significant
      BD response were characterized by a higher prevalence of dyspnea (72% versus 57%,
      P=0.02) but less cough (55% versus 75%, P=0.001) when compared with COPD subjects
      without BD reversibility. CONCLUSION: Administration of a BD in COPD case finding
      is important in order to determine the post-BD FEV1/FVC ratio. Exclusion of
      subjects with a significant BD response may result in underdiagnosis of COPD, and
      we question the need for the BD reversibility test in the diagnostic screening
      algorithm in early COPD case finding.

PMID- 25759574
TI  - Treatment patterns of chronic obstructive pulmonary disease in employed adults in
      the United States.
AB  - BACKGROUND: This study evaluated patterns of pharmacotherapy in chronic
      obstructive pulmonary disease (COPD) as they relate to recommended guidelines in
      a prevalent COPD patient population with employer-sponsored health insurance in
      the US. METHODS: Health care claims data from 2007 and 2008 were retrospectively
      analyzed for the study population defined as patients aged 40 years and older,
      continuously enrolled during the study period, and having at least one inpatient
      or one emergency department (ED) visit, or at least two outpatient claims coded
      with COPD (International Classification of Diseases, 9th Revision, Clinical
      Modification code 491.xx, 492.xx, 496.xx). Rates of any pharmacotherapy (both
      maintenance and reliever), long-acting maintenance pharmacotherapy in patients
      with an exacerbation history, and short-term treatment of acute exacerbations of
      COPD were evaluated in the overall population, newly diagnosed, and previously
      diagnosed patients (including maintenance-naive and maintenance-experienced).
      Stratified analyses were also conducted by age group (40-64 years, >=65 years)
      and physician specialty. RESULTS: A total of 55,361 patients met study criteria
      of whom 39% were newly diagnosed. The mean age was 66 years, and 46% were male.
      Three-fourths (74%) of all COPD patients had some pharmacotherapy (maintenance or
      reliever) with less than half (45%) being treated with maintenance medications.
      The combination of an inhaled corticosteroid and a long-acting beta-agonist was
      the most prevalent drug class for maintenance treatment followed by tiotropium.
      Only 64% of patients with an exacerbation history had a prescription for a long
      acting maintenance medication, and short-term treatment with oral corticosteroids
      or antibiotics was higher for hospitalization exacerbations compared to ED visit
      exacerbations (68% vs 44%). In general, the rates of pharmacotherapy were highest
      in patients who were maintenance-experienced followed by newly diagnosed and
      maintenance-naive. CONCLUSION: The majority of COPD patients received maintenance
      or reliever COPD medications, but less than half received guideline-recommended
      care, especially those with an exacerbation history or receiving short-term
      treatment for acute exacerbations.

PMID- 25759575
TI  - Silica nanoparticles induce oxidative stress, inflammation, and endothelial
      dysfunction in vitro via activation of the MAPK/Nrf2 pathway and nuclear factor
      kappaB signaling.
AB  - Despite the widespread application of silica nanoparticles (SiNPs) in industrial,
      commercial, and biomedical fields, their response to human cells has not been
      fully elucidated. Overall, little is known about the toxicological effects of
      SiNPs on the cardiovascular system. In this study, SiNPs with a 58 nm diameter
      were used to study their interaction with human umbilical vein endothelial cells
      (HUVECs). Dose- and time-dependent decrease in cell viability and damage on cell
      plasma-membrane integrity showed the cytotoxic potential of the SiNPs. SiNPs were
      found to induce oxidative stress, as evidenced by the significant elevation of
      reactive oxygen species generation and malondialdehyde production and
      downregulated activity in glutathione peroxidase. SiNPs also stimulated release
      of cytoprotective nitric oxide (NO) and upregulated inducible nitric oxide
      synthase (NOS) messenger ribonucleic acid, while downregulating endothelial NOS
      and ET-1 messenger ribonucleic acid, suggesting that SiNPs disturbed the NO/NOS
      system. SiNP-induced oxidative stress and NO/NOS imbalance resulted in
      endothelial dysfunction. SiNPs induced inflammation characterized by the
      upregulation of key inflammatory mediators, including IL-1beta, IL-6, IL-8,
      TNFalpha, ICAM-1, VCAM-1, and MCP-1. In addition, SiNPs triggered the activation
      of the Nrf2-mediated antioxidant system, as evidenced by the induction of nuclear
      factor-kappaB and MAPK pathway activation. Our findings demonstrated that SiNPs
      could induce oxidative stress, inflammation, and NO/NOS system imbalance, and
      eventually lead to endothelial dysfunction via activation of the MAPK/Nrf2
      pathway and nuclear factor-kappaB signaling. This study indicated a potential
      deleterious effect of SiNPs on the vascular endothelium, which warrants more
      careful assessment of SiNPs before their application. 

PMID- 25759576
TI  - Oral lipid-based nanoformulation of tafenoquine enhanced bioavailability and
      blood stage antimalarial efficacy and led to a reduction in human red blood cell
      loss in mice.
AB  - Tafenoquine (TQ), a new synthetic analog of primaquine, has relatively poor
      bioavailability and associated toxicity in glucose-6-phosphate dehydrogenase
      (G6PD)-deficient individuals. A microemulsion formulation of TQ (MTQ) with sizes
      <20 nm improved the solubility of TQ and enhanced the oral bioavailability from
      55% to 99% in healthy mice (area under the curve 0 to infinity: 11,368+/-1,232
      and 23,842+/-872 min.MUmol/L) for reference TQ and MTQ, respectively. Average
      parasitemia in Plasmodium berghei-infected mice was four- to tenfold lower in the
      MTQ-treated group. In vitro antiplasmodial activities against chloroquine
      sensitive and chloroquine-resistant strains of Plasmodium falciparum indicated no
      change in half maximal inhibitory concentration, suggesting that the
      microemulsion did not affect the inherent activity of TQ. In a humanized mouse
      model of G6PD deficiency, we observed reduction in toxicity of TQ as delivered by
      MTQ at low but efficacious concentrations of TQ. We hereby report an enhancement
      in the solubility, bioavailibility, and efficacy of TQ against blood stages of
      Plasmodium parasites without a corresponding increase in toxicity. 

PMID- 25759577
TI  - Exceedingly biocompatible and thin-layered reduced graphene oxide nanosheets
      using an eco-friendly mushroom extract strategy.
AB  - PURPOSE: A simple, one-pot strategy was used to synthesize reduced graphene oxide
      (RGO) nanosheets by utilizing an easily available over-the-counter medicinal and
      edible mushroom, Ganoderma lucidum. METHODS: The mushroom was boiled in hot water
      to liberate the polysaccharides, the extract of which was then used directly for
      the reduction of graphene oxide. The abundance of polysaccharides present in the
      mushroom serves as a good reducing agent. The proposed strategy evades the use of
      harmful and expensive chemicals and avoids the typical tedious reaction methods.
      RESULTS: More importantly, the mushroom extract can be easily separated from the
      product without generating any residual byproducts and can be reused at least
      three times with good conversion efficiency (75%). It was readily dispersible in
      water without the need of ultrasonication or any surfactants; whereas 5 minutes
      of ultrasonication with various solvents produced RGO which was stable for the
      tested period of 1 year. Based on electrochemical measurements, the followed
      method did not jeopardize RGO's electrical conductivity. Moreover, the obtained
      RGO was highly biocompatible to not only colon (HT-29) and brain (U87MG) cancer
      cells, but was also viable towards normal cells (MRC-5). CONCLUSION: Besides
      being eco-friendly, this mushroom based approach is easily scalable and
      demonstrates remarkable RGO stability and biocompatibility, even without any form
      of functionalization.

PMID- 25759578
TI  - Analyses of protein corona on bare and silica-coated gold nanorods against four
      mammalian cells.
AB  - The purpose of this study was to investigate the mechanisms responsible for the
      toxic effects of gold nanorods (AuNRs). Here, a comprehensive study was performed
      by examining the effects of bare (uncoated) AuNRs and AuNRs functionalized with
      silica (SiO2-AuNRs) against various mammalian cell lines, including cervical
      cancer cells, fibroblast cells, human umbilical vein endothelial cells, and
      neuroblastoma cells. The interactions between AuNRs and mammalian cells were
      investigated with cell viability and mortality assays. Dihydrorhodamine-123 assay
      was carried out for evaluating reactive oxygen species (ROS) generation, along
      with mass spectroscopy analysis for determining the composition of the protein
      corona. Our results suggest that even the lowest concentrations of AuNRs (0.7
      MUg/mL) induced ROS production leading to cell mortality. On the other hand,
      cellular viability and ROS production were maintained even at a higher
      concentration of SiO2-coated AuNRs (12 MUg/mL). The increased production of ROS
      by AuNRs seemed to cause the toxicity observed in all four mammalian cell types.
      The protein corona on the bare AuNRs did not appear to reduce ROS generation;
      however, different compositions of the protein corona on bare and SiO2-coated
      AuNRs may affect cellular behavior differently. Therefore, it was determined that
      SiO2-coated AuNRs would be more advantageous than bare AuNRs for cellular
      applications. 

PMID- 25759579
TI  - Uptake of bright fluorophore core-silica shell nanoparticles by biological
      systems.
AB  - Nanoparticles are used in a variety of consumer applications. Silica
      nanoparticles in particular are common, including as a component of foods. There
      are concerns that ingested nano-silica particles can cross the intestinal
      epithelium, enter the circulation, and accumulate in tissues and organs. Thus,
      tracking these particles is of interest, and fluorescence spectroscopic methods
      are well-suited for this purpose. However, nanosilica is not fluorescent. In this
      article, we focus on core-silica shell nanoparticles, using fluorescent Rhodamine
      6G, Rhodamine 800, or CdSe/CdS/ZnS quantum dots as the core. These stable
      fluorophore/silica nanoparticles had surface characteristics similar to those of
      commercial silica particles. Thus, they were used as model particles to examine
      internalization by cultured cells, including an epithelial cell line relevant to
      the gastrointestinal tract. Finally, these particles were administered to mice by
      gavage, and their presence in various organs, including stomach, small intestine,
      cecum, colon, kidney, lung, brain, and spleen, was examined. By combining
      confocal fluorescence microscopy with inductively coupled plasma mass
      spectrometry, the presence of nanoparticles, rather than their dissolved form,
      was established in liver tissues. 

PMID- 25759580
TI  - Layered nanoemulsions as mucoadhesive buccal systems for controlled delivery of
      oral cancer therapeutics.
AB  - Oral cavity and oropharyngeal cancers are considered the eighth most common
      cancer worldwide, with relatively poor prognosis (62% of patients surviving 5
      years, after diagnosis). The aim of this study was to develop a proof-of-concept
      mucoadhesive lozenge/buccal tablet, as a potential platform for direct sustained
      delivery of therapeutic antimitotic nanomedicines. Our system would serve as an
      adjuvant therapy for oral cancer patients undergoing full-scale diagnostic and
      operative treatment plans. We utilized lipid-based nanocarriers, namely
      nanoemulsions (NEs), containing mixed-polyethoxylated emulsifiers and a
      tocopheryl moiety-enriched oil phase. Prototype NEs, loaded with the proapoptotic
      lipophilic drug genistein (Gen), were further processed into buccal tablet
      formulations. The chitosan polyelectrolyte solution overcoat rendered NE droplets
      cationic, by acting as a mucoadhesive interfacial NE layer. With approximate size
      of 110 nm, the positively charged chitosan-layered NE (+25 mV) vs negatively
      charged chitosan-free/primary aqueous NE (-28 mV) exhibited a controlled-release
      profile and effective mucoadhesion for liquid oral spray prototypes. When punch
      pressed, porous NE-based buccal tablets were physically evaluated for hardness,
      friability, and swelling in addition to ex vivo tissue mucoadhesion force and
      retention time measurements. Chitosan-containing NE tablets were found equivalent
      to primary NE and placebo tablets in compression tests, yet significantly
      superior in all ex vivo adhesion and in vitro release assays (P<=0.05). Following
      biocompatibility screening of prototype chitosan-layered NEs, substantial
      anticancer activity of selected cationic Gen-loaded NE formulations, against two
      oropahryngeal carcinomas, was observed. The data strongly indicate the potential
      of such nanomucoadhesive systems as maintenance therapy for oral cancer patients
      awaiting surgical removal, or postresection of identified cancerous lesions. 

PMID- 25759581
TI  - In vitro and in vivo effects of graphene oxide and reduced graphene oxide on
      glioblastoma.
AB  - Graphene and its related counterparts are considered the future of advanced
      nanomaterials owing to their exemplary properties. However, information about
      their toxicity and biocompatibility is limited. The objective of this study is to
      evaluate the toxicity of graphene oxide (GO) and reduced graphene oxide (rGO)
      platelets, using U87 and U118 glioma cell lines for an in vitro model and U87
      tumors cultured on chicken embryo chorioallantoic membrane for an in vivo model.
      The in vitro investigation consisted of structural analysis of GO and rGO
      platelets using transmission electron microscopy, evaluation of cell morphology
      and ultrastructure, assessment of cell viability by XTT assay, and investigation
      of cell proliferation by BrdU assay. Toxicity in U87 glioma tumors was evaluated
      by calculation of weight and volume of tumors and analyses of ultrastructure,
      histology, and protein expression. The in vitro results indicate that GO and rGO
      enter glioma cells and have different cytotoxicity. Both types of platelets
      reduced cell viability and proliferation with increasing doses, but rGO was more
      toxic than GO. The mass and volume of tumors were reduced in vivo after injection
      of GO and rGO. Moreover, the level of apoptotic markers increased in rGO-treated
      tumors. We show that rGO induces cell death mostly through apoptosis, indicating
      the potential applicability of graphene in cancer therapy.

PMID- 25759582
TI  - Detection of hepatitis C virus core protein in serum by atomic force microscopy
      combined with mass spectrometry.
AB  - A method for detection and identification of core antigen of hepatitis C virus
      (HCVcoreAg)-containing particles in the serum was proposed, with due account
      taken of the interactions of proteotypic peptides with Na(+), K(+), and Cl(-)
      ions. The method is based on a combination of reversible biospecific atomic force
      microscopy (AFM)-fishing and mass spectrometry (MS). AFM-fishing enables
      concentration, detection, and counting of protein complexes captured on the AFM
      chip surface, with their subsequent MS identification. Biospecific AFM-fishing of
      HCVcoreAg-containing particles from serum samples was carried out using AFM chips
      with immobilized antibodies against HCVcoreAg (HCVcoreAgim). Formation of
      complexes between anti-HCVcoreAgim and HCVcoreAg-containing particles on the AFM
      chip surface during the fishing process was demonstrated. These complexes were
      registered and counted by AFM. Further MS analysis allowed reliable
      identification of HCVcoreAg within the complexes formed on the AFM chip surface.
      It was shown that MS data processing, with account taken of the interactions
      between HCVcoreAg peptides and Na(+), K(+) cations, and Cl(-) anions, allows an
      increase in the number of peptides identified. 

PMID- 25759583
TI  - Temperature-dependent and time-dependent effects of hyperthermia mediated by
      dextran-coated La0.7Sr0.3MnO3: in vitro studies.
AB  - BACKGROUND: The purpose of this study was to investigate the therapeutic efficacy
      of dextran-coated (Dex) La0.7Sr0.3MnO3 (LSMO) nanoparticles-mediated hyperthermia
      at different temperatures (43 degrees C, 45 degrees C, and 47 degrees C) based on
      cell killing potential and induction of heat shock proteins in a murine melanoma
      cell (B16F1) line. METHODS: LSMO nanoparticles were synthesized by a citrate-gel
      method and coated with dextran. B16F1 cells were exposed to the Dex-LSMO
      nanoparticles and heated using a radiofrequency generator. After heating, the
      morphology and topology of the cells were investigated by optical microscopy and
      atomic force microscopy. At 0 hours and 24 hours post heating, cells were
      harvested and viability was analyzed by the Trypan blue dye exclusion method.
      Apoptosis and DNA fragmentation were assessed by terminal deoxynucleotidyl
      transferase-dUTP nick end labeling (TUNEL) assay and agarose gel electrophoresis,
      respectively. An enzyme-linked immunosorbent assay was used to quantify heat
      shock protein levels. RESULTS: Our data indicate that cell death and induction of
      heat shock proteins in melanoma cells increased in a time-dependent and
      temperature-dependent manner, particularly at temperatures higher than 43 degrees
      C. The mode of cell death was found to be apoptotic, as evident by DNA
      fragmentation and TUNEL signal. A minimum temperature of 45 degrees C was
      required to irreversibly alter cell morphology, significantly reduce cell
      viability, and result in 98% apoptosis. Repeated cycles of hyperthermia could
      induce higher levels of heat shock proteins (more favorable for antitumor
      activity) when compared with a single cycle. CONCLUSION: Our findings indicate a
      potential use for Dex-LSMO-mediated hyperthermia in the treatment of melanoma and
      other types of cancer.

PMID- 25759584
TI  - Mixed nanomicelles as potential carriers for systemic delivery of Z-GP-Dox, an
      FAPalpha-based doxorubicin prodrug: formulation and pharmacokinetic evaluation.
AB  - Z-GP-Dox, the FAPalpha (fibroblast activation protein-alpha)-based doxorubicin
      prodrug, demonstrates excellent tumor targeting effects and a favorable
      toxicokinetic profile. However, the insoluble nature of Z-GP-Dox becomes a
      significant barrier to drug administration, particularly when it comes to the
      clinical stage. Here we developed a nanomicelle system to facilitate the systemic
      delivery of Z-GP-Dox, and evaluated its disposition in rats following
      administration of the micelles using a physiologically-based pharmacokinetic
      model. Z-GP-Dox-loaded mixed nanomicelles (ZGD-MNs) were prepared by dispersion
      of an ethanol solution of Z-GP-Dox, lecithin, and sodium oleate in water. The
      obtained ZGD-MNs were 86.6 nm in size with a drug loading of 14.03%. ZGD-MNs were
      fairly stable in phosphate-buffered saline and showed satisfactory physical and
      chemical stability over a 2-week observation period. Accumulative drug release
      was more than 56% within 24 hours. Further, the physiologically-based
      pharmacokinetic rat model consisting of various organs (ie, heart, liver, spleen,
      lung, kidney, and intestine) was fitted to the experimental data following
      administration of ZGD-loaded cosolvent (control) or micelles. Derived partition
      coefficient values revealed that the nanomicelles significantly altered the
      biodistribution of Z-GP-Dox. Of note, drug distribution to the lung, liver, and
      spleen was greatly enhanced and the fold change ranged from 2.4 to 33. In
      conclusion, this is the first report of a mixed micelle system being a viable
      carrier for delivery of Z-GP-Dox. Also, the pharmacokinetic behavior of Z-GP-Dox
      was satisfactorily described by the physiologically-based pharmacokinetic model. 

PMID- 25759585
TI  - Aripiprazole for the management of schizophrenia in the Japanese population: a
      systematic review and meta-analysis of randomized controlled trials.
AB  - BACKGROUND: We conducted a systematic review and meta-analysis of randomized
      controlled trials comparing aripiprazole with pooled antipsychotics in Japanese
      patients with schizophrenia. METHODS: We performed a literature search of data
      published in PubMed((r)), the Cochrane Library database, the Japan Medical
      Abstracts Society, and PsycINFO((r)) up to January 5, 2014. The odds ratio (OR),
      number-needed-to-harm (NNH), and standardized mean difference (SMD) based on a
      random effects model were calculated. RESULTS: We identified five relevant
      studies (seven comparisons, n=684; one comparison each for haloperidol [n=243],
      mosapramine [n=238], olanzapine [n=39], quetiapine [n=42], perospirone [n=100],
      and two comparisons for risperidone [n=66]). There were no significant
      differences in the Positive and Negative Syndrome Scale (PANSS) total, negative,
      and general scores (SMD=0.10, SMD=-0.09, SMD=0.10, respectively); discontinuation
      rate associated with all causes (OR=1.35); or side effects (OR=1.03) between
      aripiprazole and the pooled antipsychotics. Aripiprazole was inferior to the
      pooled antipsychotics in PANSS positive subscale scores (SMD=0.17) and
      discontinuation because of inefficacy (OR=2.21, NNH=11). However, aripiprazole
      had fewer side effects compared with the pooled antipsychotics (OR=0.21, NNH=20
      for one or more side effects), including fatigue (OR=0.22, NNH=8),
      hyperprolactinemia (OR=0.00, NNH=1), extrapyramidal symptoms (OR=0.46, NNH=6),
      and weight gain (OR=0.36, NNH=7). Moreover, aripiprazole was associated with
      lower total cholesterol (SMD=-0.20) and triglyceride (SMD=-0.17) levels and body
      weight (SMD=-0.20) compared with the pooled antipsychotics. CONCLUSION: Although
      the discontinuation rate associated with inefficacy was higher with aripiprazole
      than with the pooled antipsychotics, aripiprazole was associated with a lower
      risk of hyperprolactinemia and metabolic and extrapyramidal symptoms compared
      with the pooled antipsychotics.

PMID- 25759586
TI  - Safety and effectiveness of controlled-release paroxetine in routine clinical
      practice: results of a postmarketing surveillance study of patients with
      depression.
AB  - OBJECTIVE: Selective serotonin reuptake inhibitors are commonly used in the
      pharmacotherapy of depression. However, adverse events can lead to their early
      discontinuation. This study evaluated the safety and effectiveness of paroxetine
      controlled-release (CR) tablets in Japanese patients with depression/depressive
      state (hereafter referred to as depression) in routine clinical practice in
      Japan. PATIENTS AND METHODS: This was an open-label, noninterventional,
      prospective, postmarketing surveillance study. A total of 3,213 patients aged 12
      92 years with depression were prescribed paroxetine CR for 8 weeks at the
      physician's discretion. Safety was evaluated on the basis of the reporting of
      adverse drug reactions. Effectiveness was evaluated on the basis of the
      physician's assessment using the Clinical Global Impression-Global Improvement
      (CGI-GI) and the Clinical Global Impression-Severity of Illness (CGI-SI) scales,
      as well as on the basis of the patients' self-reported satisfaction. The primary
      effectiveness outcome was the improvement rate based on the physician's
      assessment using the CGI-GI. RESULTS: The incidence of adverse drug reactions was
      11.2% (359/3,213; 95% confidence interval [CI]: 10.1%-12.3%). The common adverse
      drug reactions that accounted for 1.0% or more of the incidence were nausea
      (3.5%) and somnolence (2.7%). The proportion of patients who continued paroxetine
      CR at week 8 was 80.2% (2,577/3,213; 95% CI: 78.8%-81.6%). The improvement rate
      at week 8 (last observation carried forward) was 72.8% (2,132/2,927; 95% CI:
      71.2%-74.4%). The proportion of patients with CGI-SI scores of moderately or
      severely ill decreased from 63.6% at baseline to 17.9% at week 8. The proportion
      of patients who were satisfied with paroxetine CR treatment was 69.8%
      (2,040/2,921; 95% CI: 68.1%-71.5%). CONCLUSION: The results of this study suggest
      that paroxetine CR is a well-tolerated and efficacious treatment for depression
      in routine clinical practice.

PMID- 25759587
TI  - Influence of 5-HT1A and 5-HTTLPR genetic variants on the schizophrenia symptoms
      and occurrence of treatment-resistant schizophrenia.
AB  - This study aimed to explore the influence of two genetic polymorphisms of the 5
      hydroxytryptamine 1A receptor (5-HT1A) and solute carrier family 6, member 4
      (SLC6A4) genes on the clinical symptoms and treatment resistance in Slovenian
      patients with schizophrenia. A total of 138 patients with schizophrenia were
      evaluated using the Positive and Negative Syndrome Scale, Brief Psychiatric
      Rating Scale, Clinical Global Impression, and Global Assessment of Functioning.
      Based on the selected criteria, 94 patients were included in the treatment
      responsive and 44 in the treatment-resistant group. All subjects and 94 controls
      were genotyped for the 5-HT1A rs6295 and 5-HTTLPR polymorphisms. There were no
      statistically significant differences in the frequencies of these polymorphisms
      between the patients with schizophrenia and the control group and between the
      treatment-resistant and treatment-responsive group of schizophrenia patients.
      Polymorphisms rs6295 and 5-HTTLPR had an influence on the Global Assessment of
      Functioning scale score, while 5-HTTLPR also had an influence on the total score
      of the negative subscale within the Positive and Negative Syndrome Scale.
      Although we found no effect on progression toward the treatment-resistant
      schizophrenia, our data suggest that the rs6295 and 5-HTTLPR polymorphisms can
      influence some clinical symptoms in schizophrenia. 

PMID- 25759588
TI  - Physiotherapy for human T-lymphotropic virus 1-associated myelopathy: review of
      the literature and future perspectives.
AB  - Human T-lymphotropic virus 1 (HTLV-1) infection may be associated with damage to
      the spinal cord - HTLV-associated myelopathy/tropical spastic paraparesis - and
      other neurological symptoms that compromise everyday life activities. There is no
      cure for this disease, but recent evidence suggests that physiotherapy may help
      individuals with the infection, although, as far as we are aware, no systematic
      review has approached this topic. Therefore, the objective of this review is to
      address the core problems associated with HTLV-1 infection that can be detected
      and treated by physiotherapy, present the results of clinical trials, and discuss
      perspectives on the development of knowledge in this area. Major problems for
      individuals with HTLV-1 are pain, sensory-motor dysfunction, and urinary
      symptoms. All of these have high impact on quality of life, and recent clinical
      trials involving exercises, electrotherapeutic modalities, and massage have shown
      promising effects. Although not influencing the basic pathologic disturbances, a
      physiotherapeutic approach seems to be useful to detect specific problems related
      to body structures, activity, and participation related to movement in HTLV-1
      infection, as well as to treat these conditions. 

PMID- 25759589
TI  - Epigallocatechin-3-gallate suppresses cell proliferation and promotes apoptosis
      and autophagy in oral cancer SSC-4 cells.
AB  - Epigallocatechin-3-gallate (EGCG) is the major bioactive component of green tea.
      Our experimental data indicated that EGCG treatment suppresses cell proliferation
      of SSC-4 human oral squamous cell carcinoma (OSCC), the effect being dose- and
      time-dependent. In parallel was observed the activation of apoptosis and
      autophagy, in response to EGCG exposure in SSC-4 cells. Treatment with EGCG
      activates the expression of the BAD, BAK, FAS, IGF1R, WNT11, and ZEB1 genes and
      inhibits CASP8, MYC, and TP53. All of these results suggest that EGCG has an
      excellent potential to become a therapeutic compound for patients with OSCC, by
      inducing tumor cell death via apoptosis and autophagy. 

PMID- 25759590
TI  - Medical resource utilization and costs associated with autosomal dominant
      polycystic kidney disease in the USA: a retrospective matched cohort analysis of
      private insurer data.
AB  - BACKGROUND: Autosomal dominant polycystic kidney disease (ADPKD) results in
      kidney cyst development and enlargement, resulting in chronic kidney disease
      (CKD) leading to renal failure. This study sought to determine if ADPKD patients
      in the early stages of CKD contribute to a sizable economic burden for the US
      health care system. METHODS: This was a retrospective, matched cohort study,
      reviewing medical resource utilization (MRU) and costs for adults in a US private
      payer claims database with a diagnosis code of ADPKD (ICD-9-CM 753.13). ADPKD
      patients were matched by age grouping (0-17, 18-34, 35-44, 45-54, 55-64, and 65+
      years) and sex to controls to understand the burden of ADPKD. Descriptive
      statistics on 6-month MRU and costs were assessed by CKD stages, dialysis use, or
      previous renal transplant. RESULTS: The analysis included ADPKD patients in CKD
      stages 1-5 (n=316 to n=860), dialysis (n=586), and post-transplant (n=615). Mean
      ages did not differ across CKD stages (range 43-56 years). Men were the majority
      in the later stages but the minority in the early stages. The proportion of
      patients with at least one hospitalization increased with CKD stage, (12% to >40%
      CKD stage 2 to stage 5, dialysis or post-transplant). The majority had at least
      one hospital outpatient visit and at least one pharmacy claim. Total 6-month per
      patient costs were greater among ADPKD patients than in age-matched and sex
      matched healthy non-ADPKD controls (P<0.001 for all comparisons). CONCLUSION:
      ADPKD patients with normal kidney function are associated with a significant
      economic burden to the health care system relative to the general population. Any
      treatments that delay progression to later stages of CKD may provide potential
      health care cost offsets.

PMID- 25759591
TI  - Sotagliflozin improves glycemic control in nonobese diabetes-prone mice with type
      1 diabetes.
AB  - PURPOSE: Oral agents are needed that improve glycemic control without increasing
      hypoglycemic events in patients with type 1 diabetes (T1D). Sotagliflozin may
      meet this need, because this compound lowers blood glucose through the insulin
      independent mechanisms of inhibiting kidney SGLT2 and intestinal SGLT1. We
      examined the effect of sotagliflozin on glycemic control and rate of hypoglycemia
      measurements in T1D mice maintained on a low daily insulin dose, and compared
      these results to those from mice maintained in better glycemic control with a
      higher daily insulin dose alone. MATERIALS AND METHODS: Nonobese diabetes-prone
      mice with cyclophosphamide-induced T1D were randomized to receive one of four
      daily treatments: 0.2 U insulin/vehicle, 0.05 U insulin/vehicle, 0.05 U insulin/2
      mg/kg sotagliflozin or 0.05 U insulin/30 mg/kg sotagliflozin. Insulin was
      delivered subcutaneously by micro-osmotic pump; the day after pump implantation,
      mice received their first of 22 once-daily oral doses of sotagliflozin or
      vehicle. Glycemic control was monitored by measuring fed blood glucose and
      hemoglobin A1c levels. RESULTS: Blood glucose levels decreased rapidly and
      comparably in the 0.05 U insulin/sotagliflozin-treated groups and the 0.2 U
      insulin/vehicle group compared to the 0.05 U insulin/vehicle group, which had
      significantly higher levels than the other three groups from day 2 through day
      23. A1c levels were also significantly higher in the 0.05 U insulin/vehicle group
      compared to the other three groups on day 23. Importantly, the 0.2 U
      insulin/vehicle group had, out of 100 blood glucose measurements, 13 that were
      <70 mg/dL compared to one of 290 for the other three groups combined. CONCLUSION:
      Sotagliflozin significantly improved glycemic control, without increasing the
      rate of hypoglycemia measurements, in diabetic mice maintained on a low insulin
      dose. This sotagliflozin-mediated improvement in glycemic control was comparable
      to that achieved by raising the insulin dose alone, but was not accompanied by
      the increased rate of hypoglycemia measurements observed with the higher insulin
      dose.

PMID- 25759592
TI  - Urinary tract infections in patients with type 2 diabetes mellitus: review of
      prevalence, diagnosis, and management.
AB  - Urinary tract infections are more common, more severe, and carry worse outcomes
      in patients with type 2 diabetes mellitus. They are also more often caused by
      resistant pathogens. Various impairments in the immune system, poor metabolic
      control, and incomplete bladder emptying due to autonomic neuropathy may all
      contribute to the enhanced risk of urinary tract infections in these patients.
      The new anti-diabetic sodium glucose cotransporter 2 inhibitors have not been
      found to significantly increase the risk of symptomatic urinary tract infections.
      Symptoms of urinary tract infection are similar to patients without diabetes,
      though some patients with diabetic neuropathy may have altered clinical signs.
      Treatment depends on several factors, including: presence of symptoms, severity
      of systemic symptoms, if infection is localized in the bladder or also involves
      the kidney, presence of urologic abnormalities, accompanying metabolic
      alterations, and renal function. There is no indication to treat diabetic
      patients with asymptomatic bacteriuria. Further studies are needed to improve the
      treatment of patients with type 2 diabetes and urinary tract infections. 

PMID- 25759593
TI  - Effects of plant sterols derived from Aloe vera gel on human dermal fibroblasts
      in vitro and on skin condition in Japanese women.
AB  - BACKGROUND: Aloe is known for its topical use for treating wounds and burns. Many
      previous studies reported the healing effects of Aloe vera. However, there are
      few clinical studies on the effect of orally administered A. vera gel on the
      skin. Aloe sterols are a type of plant sterols that have the capability to
      regulate the metabolism of glucose and lipids. In a recent study, we confirmed
      that ingested Aloe sterols reached the peripheral tissues through the
      bloodstream. However, their influence on dermal fibroblasts has not been
      investigated. METHODS: First, we investigated the capability of Aloe sterols
      (cycloartenol and lophenol) to stimulate human dermal fibroblasts in vitro. Then,
      we investigated the effect of intake of Aloe vera gel powder (AVGP) containing 40
      MUg Aloe sterols on the skin conditions in Japanese women with dry skin in a
      randomized, double-blind, placebo-controlled trial. RESULTS: After cocultivation
      with Aloe sterols, the production of collagen and hyaluronic acid increased by
      approximately two-fold and 1.5-fold, and gene expression levels of these enzymes
      responsible for their synthesis were also observed in human dermal fibroblasts.
      An increase in arm skin hydration was observed at 8 weeks in the AVGP group,
      whereas a slight decrease in arm skin hydration was noted in the placebo group.
      However, there was no statistical difference between AVGP and placebo groups in
      skin moisture. In subgroup analysis, the change in the mean wrinkle depth was
      significantly lower in the AVGP group than in the control group. In addition,
      percent body fat after 8 weeks was significantly lower in the AVGP group. No AVGP
      intake-dependent harmful phenomenon was observed during the intake period.
      CONCLUSION: The present study confirms that daily oral Aloe sterol-containing
      AVGP significantly reduced facial wrinkles in women aged >=40 years, and Aloe
      sterols stimulate collagen and hyaluronic acid production by human dermal
      fibroblasts.

PMID- 25759594
TI  - Scabies among primary schoolchildren in Egypt: sociomedical environmental study
      in Kafr El-Sheikh administrative area.
AB  - BACKGROUND/OBJECTIVES: Scabies is a major global public health issue that might
      affect people from all socioeconomic levels. The primary contributing factors in
      contracting scabies seem to be poverty and overcrowded living conditions. Scabies
      often spreads among schoolchildren quite rapidly, owing to their close contact
      and overcrowding within the schools. However, limited information is available
      about its risk factors and the socioeconomic correlates among schoolchildren in
      Egypt. This study aimed to assess the prevalence of scabies and its risk factors
      among primary schoolchildren in Kafr El-Sheikh administrative area, Egypt.
      METHODS: This cross-sectional descriptive study was performed on primary
      schoolchildren in urban and rural areas of Kafr El-Sheikh administrative area. A
      predesigned questionnaire was used for data collection from the randomly selected
      2,104 children, and clinical dermatological examination was done for them.
      RESULTS: Out of 2,104 children studied, there were 92 cases of scabies with a
      prevalence of 4.4%. The prevalence of scabies infestation in male students was
      3.9%, while it was 4.8% in females, with no statistical significance. The results
      showed significant variations in the risk of scabies infestation by factors such
      as residence, paternal education and occupation, maternal education, sleeping
      with others, having animals at home, dealing with animals outside the house, type
      of building for living, family history of itchy rash, and sharing clothes with
      others. CONCLUSION: In our community, scabies is still an important health
      problem affecting schoolchildren, especially in rural areas. It is characterized
      by a complex web of causation, particularly poor living conditions and low level
      of parents' education.

PMID- 25759596
TI  - Association between education and quality of diabetes care in Switzerland.
AB  - PURPOSE: Low socioeconomic status is associated with higher prevalence of
      diabetes, worse outcomes, and worse quality of care. We explored the relationship
      between education, as a measure of socioeconomic status, and quality of care in
      the Swiss context. PATIENTS AND METHODS: Data were drawn from a population-based
      survey of 519 adults with diabetes during fall 2011 and summer 2012 in a canton
      of Switzerland. We assessed patients and diabetes characteristics. Eleven
      indicators of quality of care were considered (six of process and five of
      outcomes of care). After bivariate analyses, regression analyses adjusted for
      age, sex, and diabetic complications were performed to assess the relationship
      between education and quality of care. RESULTS: Of 11 quality-of-care indicators,
      three were significantly associated with education: funduscopy (patients with
      tertiary versus primary education were more likely to get the exam: odds ratio,
      1.8; 95% confidence interval [CI], 1.004-3.3) and two indicators of health
      related quality of life (patients with tertiary versus primary education reported
      better health-related quality of life: Audit of Diabetes-Dependent Quality of
      Life: beta=0.6 [95% CI, 0.2-0.97]; SF-12 mean physical component summary score:
      beta=3.6 [95% CI, 0.9-6.4]). CONCLUSION: Our results suggest the presence of
      educational inequalities in quality of diabetes care. These findings may help
      health professionals focus on individuals with increased needs to decrease health
      inequalities.

PMID- 25759595
TI  - Effect of pulsed electromagnetic field treatment on programmed resolution of
      inflammation pathway markers in human cells in culture.
AB  - Inflammation is a complex process involving distinct but overlapping biochemical
      and molecular events that are highly regulated. Pulsed electromagnetic field
      (PEMF) therapy is increasingly used to treat pain and edema associated with
      inflammation following surgery involving soft tissue. However, the molecular and
      cellular effects of PEMF therapy on pathways involved in the resolution of
      inflammation are poorly understood. Using cell culture lines relevant to trauma
      induced inflammation of the skin (human dermal fibroblasts, human epidermal
      keratinocytes, and human mononuclear cells), we investigated the effect of PEMF
      on gene expression involved in the acute and resolution phases of inflammation.
      We found that PEMF treatment was followed by changes in the relative amount of
      messenger (m)RNAs encoding enzymes involved in heme catabolism and removal of
      reactive oxygen species, including an increase in heme oxygenase 1 and superoxide
      dismutase 3 mRNAs, in all cell types examined 2 hours after PEMF treatment. A
      relative increase in mRNAs encoding enzymes involved in lipid mediator
      biosynthesis was also observed, including an increase in arachidonate 12- and 15
      lipoxygenase mRNAs in dermal fibroblasts and epidermal keratinocytes,
      respectively. The relative amount of both of these lipoxygenase mRNAs was
      elevated in mononuclear cells following PEMF treatment relative to nontreated
      cells. PEMF treatment was also followed by changes in the mRNA levels of several
      cytokines. A decrease in the relative amount of interleukin 1 beta mRNA was
      observed in mononuclear cells, similar to that previously reported for epidermal
      keratinocytes and dermal fibroblasts. Based on our results, we propose a model in
      which PEMF therapy may promote chronic inflammation resolution by mediating gene
      expression changes important for inhibiting and resolving inflammation. 

PMID- 25759597
TI  - Grading the intensity of nondental orofacial pain: identification of cutoff
      points for mild, moderate, and severe pain.
AB  - BACKGROUND: When assessing pain in clinical practice, clinicians often label pain
      as mild, moderate, and severe. However, these categories are not distinctly
      defined, and are often used arbitrarily. Instruments for pain assessment use more
      sophisticated scales, such as a 0-10 numerical rating scale, and apart from pain
      intensity assess pain-related interference and disability. The aim of the study
      was to identify cutoff points for mild, moderate, and severe nondental orofacial
      pain using a numerical rating scale, a pain-related interference scale, and a
      disability measurement. MATERIALS AND METHODS: A total of 245 patients referred
      to the Facial Pain Unit in London were included in the study. Intensity and pain
      related interference were assessed by the Brief Pain Inventory. Pain-related
      disability was assessed by the Chronic Graded Pain Scale. Average pain intensity
      (0-10) was classified into nine schemes with varying cutoff points of mild,
      moderate, and severe pain. The scheme with the most significant intergroup
      difference, expressed by multivariate analysis of variance, provided the cutoffs
      between mild, moderate, and severe pain. RESULTS: The combination that showed the
      greatest intergroup differences for all patients was scheme 47 (mild 1-4,
      moderate 5-7, severe 8-10). The same combination provided the greatest intergroup
      differences in subgroups of patients with temporomandibular disorder and chronic
      idiopathic facial pain, respectively. Among the trigeminal neuralgia patients
      alone, the combination with the highest intergroup differences was scheme 48
      (mild 1-4, moderate 5-8, severe 9-10). CONCLUSION: The cutoff points established
      in this study can discriminate in pain intensity categories reasonably well, and
      showed a significant difference in most of the outcome measures used.

PMID- 25759598
TI  - New insights into the use of currently available non-steroidal anti-inflammatory
      drugs.
AB  - Non-steroidal anti-inflammatory drugs (NSAIDs), which act via inhibition of the
      cyclooxygenase (COX) isozymes, were discovered more than 100 years ago. They
      remain a key component of the pharmacological management of acute and chronic
      pain. The COX-1 and COX-2 isozymes have different biological functions; analgesic
      activity is primarily (although not exclusively) associated with inhibition of
      COX-2, while different side effects result from the inhibition of COX-1 and COX
      2. All available NSAIDs, including acetaminophen and aspirin, are associated with
      potential side effects, particularly gastrointestinal and cardiovascular effects,
      related to their relative selectivity for COX-1 and COX-2. Since all NSAIDs exert
      their therapeutic activity through inhibition of the COX isozymes, strategies are
      needed to reduce the risks associated with NSAIDs while achieving sufficient pain
      relief. A better understanding of the inhibitory activity and COX-1/COX-2
      selectivity of an NSAID at therapeutic doses, based on pharmacokinetic and
      pharmacodynamic properties (eg, inhibitory dose, absorption, plasma versus tissue
      distribution, and elimination), and the impact on drug tolerability and safety
      can guide the selection of appropriate NSAIDs for pain management. For example,
      many NSAIDs with moderate to high selectivity for COX-2 versus COX-1 can be
      administered at doses that maximize efficacy (~80% inhibition of COX-2) while
      minimizing COX-1 inhibition and associated side effects, such as gastrointestinal
      toxicity. Acidic NSAIDs with favorable tissue distribution and short plasma half
      lives can additionally be dosed to provide near-constant analgesia while
      minimizing plasma concentrations to permit recovery of COX-mediated prostaglandin
      production in the vascular wall and other organs. Each patient's clinical
      background, including gastrointestinal and cardiovascular risk factors, should be
      taken into account when selecting appropriate NSAIDs. New methods are emerging to
      assist clinicians in the selection of appropriate NSAIDs and their
      doses/schedules, such as biomarkers that may predict the response to NSAID
      treatment in individual patients. 

PMID- 25759600
TI  - Prevalence and characteristics of patients with low levels of low-density
      lipoprotein cholesterol in northern Denmark: a descriptive study.
AB  - BACKGROUND: With the emergence of new lipid-lowering therapies, more patients are
      expected to achieve substantial lowering of low-density lipoprotein cholesterol
      (LDL-C). However, there are limited data examining the clinical experience of
      patients with low (<1.3 mmol/L) or very low (<0.65 mmol/L) levels of LDL-C. To
      provide information on patients with low LDL-C, we identified and characterized
      persons with low LDL-C using data from Danish medical databases. METHODS: Using a
      population-based clinical laboratory database, we identified adults with at least
      one LDL-C measurement in northern Denmark between 1998 and 2011 (population
      approximately 1.5 million persons). Based on the lowest measurement during the
      study period, we divided patients into groups with low (<1.3 mmol/L), moderate
      (1.3-3.3 mmol/L), or high (>3.3 mmol/L) LDL-C. We described their demographic
      characteristics, entire comorbidity history, and 90-day prescription history
      prior to the lowest LDL-C value measured. Finally, we further restricted the
      analysis to individuals with very low LDL-C (<0.65 mmol/L). RESULTS: Among
      765,503 persons with an LDL-C measurement, 23% had high LDL-C, 73% had moderate
      LDL-C, and 4.8% had low LDL-C. In the latter group, 9.6% (0.46% of total) had
      very low LDL-C. Compared with the moderate and high LDL-C categories, the low LDL
      C group included more males and older persons with a higher prevalence of
      cardiovascular disease, diabetes, chronic pulmonary disease, ulcer disease, and
      obesity, as measured by hospital diagnoses or relevant prescription drugs for
      these diseases. Cancer and use of psychotropic drugs were also more prevalent.
      These patterns of distribution became even more pronounced when restricting to
      individuals with very low LDL-C. CONCLUSION: Using Danish medical databases, we
      identified a cohort of patients with low LDL-C and found that cohort members
      differed from patients with higher LDL-C levels. These differences may be
      explained by various factors, including prescribing patterns of lipid-lowering
      therapies.

PMID- 25759601
TI  - Statin prescription patterns, adherence, and attainment of cholesterol treatment
      goals in routine clinical care: a Danish population-based study.
AB  - PURPOSE: To examine the annual rate and cumulative prevalence of statin use in
      Denmark 2004-10, including adherence of use and attainment of cholesterol
      targets. METHODS: We included all individuals aged 18-86 years with a first
      statin prescription in Northern Denmark in 2004-10. We calculated the annual rate
      and cumulative prevalence of statin use. We examined cholesterol values before
      and after start of statins and the proportion reaching targets according to
      European guidelines and cardiovascular risk group. RESULTS: The study population
      consisted of 161,646 new statin users (51% men; median age 62 years). The peak
      rate of new statin initiators occurred in 2008, and a cumulative prevalence of 94
      users per 1,000 population was reached in 2010. In total, 98% of new users
      started with simvastatin. Eighty-eight percent (142,897) did not switch statin
      type during follow-up. Overall persistence was 84%. The reduction in median total
      cholesterol in new statin users was 28% (from 6.3 mmol/L to 4.5 mmol/L), while it
      was 43% (from 4.0 mmol/L to 2.3 mmol/L) for low-density lipoprotein cholesterol.
      Among patients with very high cardiovascular risk, 66% attained the recommended
      total cholesterol target; corresponding figures were 74% among high-risk patients
      and 80% among low- to moderate-risk patients. Corresponding figures for low
      density lipoprotein cholesterol were 54%, 82%, and 88%, respectively.
      CONCLUSIONS: Statin use has become very prevalent in Danish adults, with high
      adherence. Cholesterol reduction after statin initiation is similar to that found
      in clinical trials, yet a substantial proportion of patients does not reach
      target cholesterol levels.

PMID- 25759599
TI  - Critical analysis of the potential for microRNA biomarkers in breast cancer
      management.
AB  - Breast cancer is a complex and heterogeneous disease. Signaling by estrogen
      receptor (ER), progesterone receptor (PR), and/or human EGF-like receptor 2
      (HER2) is a main driver in the development and progression of a large majority of
      breast tumors. Molecular characterization of primary tumors has identified major
      subtypes that correlate with ER/PR/HER2 status, and also subgroup divisions that
      indicate other molecular and cellular features of the tumors. While some of these
      research findings have been incorporated into clinical practice, several
      challenges remain to improve breast cancer management and patient survival, for
      which the integration of novel biomarkers into current practice should be
      beneficial. microRNAs (miRNAs) are a class of short non-coding regulatory RNAs
      with an etiological contribution to breast carcinogenesis. miRNA-based diagnostic
      and therapeutic applications are rapidly emerging as novel potential approaches
      to manage and treat breast cancer. Rapid technological development enables
      specific and sensitive detection of individual miRNAs or the entire miRNome in
      tissues, blood, and other biological specimens from breast cancer patients. This
      review focuses on recent miRNA research and its potential to address unmet
      clinical needs and challenges. The four sections presented discuss miRNA findings
      in the context of the following clinical challenges: biomarkers for early
      detection; prognostic and predictive biomarkers for treatment decisions using
      targeted therapies against ER and HER2; diagnostic and prognostic biomarkers for
      subgrouping of triple-negative breast cancer, for which there are currently no
      targeted therapies; and biomarkers for monitoring and characterization of
      metastatic breast cancer. The review concludes with a critical analysis of the
      current state of miRNA breast cancer research and the need for further studies
      using large patient cohorts under well-controlled conditions before considering
      the clinical implementation of miRNA biomarkers. 

PMID- 25759602
TI  - Awareness and predictors of female genital mutilation/cutting among young health
      advocates.
AB  - The act of female genital mutilation/cutting (FGM/C) is considered
      internationally as a violent act against girls and women and a violation of their
      human rights. This study sought to assess the awareness and predictors of FGM/C
      in young Egyptian health advocates. A cross-sectional study of 600 medical
      students from a total of 2,500 members of the International Federation of Medical
      Students' Associations (IFMSA)-Egypt, across all Egyptian medical schools, was
      conducted using a previously validated online Google survey. The overall
      prevalence of circumcision was 14.7/100 female students, with a significantly
      higher prevalence in students from rural areas (25%) than in non-rural areas
      (10.8%, P=0.001), and in those residing in Upper (southern) Egypt (20.6%) than in
      Lower (northern) Egypt (8.7%, P=0.003). The students' mean percentage score for
      knowledge about the negative health consequences of FGM/C was 53.50+/-29.07,
      reflecting a modest level of knowledge; only 30.5% had a good level of knowledge.
      The mean percentage score for the overall attitude toward discontinuation of the
      practice of FGM/C was 76.29+/-17.93, reflecting a neutral attitude; 58.7% had a
      favorable attitude/norms toward discontinuation of the practice. Of circumcised
      students, approximately one-half (46.8%) were unwilling to have their daughters
      circumcised, and 60% reported no harm from being circumcised. After controlling
      for confounders, a negative attitude toward FGM/C was significantly (P<0.001 in
      all cases) associated with male sex, residency in Upper Egypt, rural origin,
      previous circumcision, and the preclinical medical phase of education. The low
      level of knowledge among even future health professions in our study suggests
      that communication, rather than passive learning, is needed to convey the
      potentially negative consequences of FGM/C and to drive a change in attitude
      toward discontinuation of this harmful practice. 

PMID- 25759603
TI  - Do medical students' scores using different assessment instruments predict their
      scores in clinical reasoning using a computer-based simulation?
AB  - PURPOSE: The development of clinical problem-solving skills evolves over time and
      requires structured training and background knowledge. Computer-based case
      simulations (CCS) have been used for teaching and assessment of clinical
      reasoning skills. However, previous studies examining the psychometric properties
      of CCS as an assessment tool have been controversial. Furthermore, studies
      reporting the integration of CCS into problem-based medical curricula have been
      limited. METHODS: This study examined the psychometric properties of using CCS
      software (DxR Clinician) for assessment of medical students (n=130) studying in a
      problem-based, integrated multisystem module (Unit IX) during the academic year
      2011-2012. Internal consistency reliability of CCS scores was calculated using
      Cronbach's alpha statistics. The relationships between students' scores in CCS
      components (clinical reasoning, diagnostic performance, and patient management)
      and their scores in other examination tools at the end of the unit including
      multiple-choice questions, short-answer questions, objective structured clinical
      examination (OSCE), and real patient encounters were analyzed using stepwise
      hierarchical linear regression. RESULTS: Internal consistency reliability of CCS
      scores was high (alpha=0.862). Inter-item correlations between students' scores
      in different CCS components and their scores in CCS and other test items were
      statistically significant. Regression analysis indicated that OSCE scores
      predicted 32.7% and 35.1% of the variance in clinical reasoning and patient
      management scores, respectively (P<0.01). Multiple-choice question scores,
      however, predicted only 15.4% of the variance in diagnostic performance scores
      (P<0.01), while students' scores in real patient encounters did not predict any
      of the CCS scores. CONCLUSION: Students' scores in OSCE are the most important
      predictors of their scores in clinical reasoning and patient management using
      CCS. However, real patient encounter assessment does not appear to test a
      construct similar to what is tested in CCS.

PMID- 25759604
TI  - Influence of predicting the diagnosis from history on the accuracy of physical
      examination.
AB  - BACKGROUND: This study aimed to clarify the influence of predicting a correct
      diagnosis from the history on physical examination by comparing the diagnostic
      accuracy of auscultation with and without clinical information. METHODS: The
      participants were 102 medical students from the 2013 clinical clerkship course.
      Auscultation was performed with a cardiology patient simulator. Participants were
      randomly assigned to two groups. Each group listened to a different simulated
      heart murmur and then made a diagnosis without clinical information. Next, a
      history suggesting a different murmur was provided to each group and they
      predicted the diagnosis. Finally, the students listened to a murmur corresponding
      to the history provided and again made a diagnosis. Correct and incorrect
      diagnosis rates of auscultation were compared between students with and without
      clinical information, between students predicting a correct or incorrect
      diagnosis from the history (correct and incorrect prediction groups,
      respectively), and between students without clinical information and those making
      an incorrect prediction. RESULTS: For auscultation with or without clinical
      information, the correct diagnosis rate was 62.7% (128/204 participants) versus
      54.4% (111/204 participants), showing no significant difference (P=0.09). After
      receiving clinical information, a correct diagnosis was made by 102/117 students
      (87.2%) in the correct prediction group versus 26/87 students (29.9%) in the
      incorrect prediction group, showing a significant difference (P=0.006). The
      correct diagnosis rate was also significantly lower in the incorrect prediction
      group than when the students performed auscultation without clinical information
      (54.4% versus 29.9%, P<0.001). CONCLUSION: Obtaining a history alone does not
      improve the diagnostic accuracy of physical examination. However, accurately
      predicting the diagnosis from the history is associated with higher diagnostic
      accuracy of physical examination, while incorrect prediction is associated with
      lower diagnostic accuracy of examination.

PMID- 25759605
TI  - Students' knowledge of, and attitudes toward, mentoring: a case study at the
      Master's Program in Health and Hospital Administration.
AB  - INTRODUCTION: Mentoring has been defined as a process whereby the mentor guides
      the mentee in personal or professional development. Few mentoring programs are
      available to prepare the qualified and scientifically trained administrators
      required to manage the rapidly expanding national health services in the Kingdom
      of Saudi Arabia. We wanted to measure the attitude and knowledge of the students
      of the Master's Program in Health and Hospital Administration toward mentoring.
      MATERIALS AND METHODS: This is a cross-sectional survey, design study, conducted
      at King Saud bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia.
      The participants were students enrolled in the master's program. The dimensions
      of the questionnaire were demographics, knowledge about mentoring, understanding
      of mentoring, perception toward mentoring, attitude toward mentoring, experience
      with mentoring, and the need of mentoring. A Likert scale was used to measure
      responses. RESULTS: Among 120 students, the response rate was 85%. In the domain
      of attitude toward mentoring, 92% of the respondents stated that mentoring is an
      effective method of developing their potential. The mean age was 30+/-4 years,
      75.5% were female, 36% had finished at least two semesters, and 92% expressed a
      strong need for mentoring in the master program. CONCLUSION: Mentorship is
      considered an important underutilized educational tool, which has great potential
      if implemented properly. Our university masters' students demonstrated a need for
      mentoring that we believe is a good platform to plan future development of
      mentorship programs.

PMID- 25759606
TI  - Intraoperative change of lactate level is associated with postoperative outcomes
      in pediatric cardiac surgery patients: retrospective observational study.
AB  - BACKGROUND: A change of serum lactate concentrations appeared to be useful for
      predicting outcomes in various acute ill settings. However, there is little
      information on intraoperative change of lactate level in pediatric cardiac
      surgery patients. METHODS: We conducted a retrospective observational study of
      459 children who received pediatric cardiac surgery to determine the association
      between change of lactate level after cardiopulmonary bypass (CPB) and patient
      prognosis (length of ICU stay and incidence of postoperative serious adverse
      events (SAEs)). We defined change of lactate level after CPB (LAC?) as (final
      lactate level measurement in the operating room) - (lactate level measured at the
      end of CPB). To study the independent association of LAC? with length of ICU
      stay, we used linear regression model. RESULTS: There were 1145 lactate
      measurements after CPB in this study cohort. After weaning from CPB, the serum
      lactate levels significantly increased from 2.1 mmol/L to 2.5 mmol/L (p < 0.001).
      Patients with higher LAC? had significantly longer stay in ICU (p = 0.017) and
      higher incidence of SAEs (p = 0.002). In multivariate linear regression analysis,
      higher LAC? showed a significant independent association with longer length of
      ICU stay. CONCLUSIONS: Increased lactate level after CPB was associated with the
      longer duration of ICU stay and increased risk of postoperative SAEs in pediatric
      cardiac surgery patients. Future studies should be conducted to determine the
      clinical utility of intraoperative trend of lactate levels.

PMID- 25759608
TI  - Integrating service user participation in mental health care: what will it take?
AB  - Participation in mental health care poses many challenges for mental health
      service users and service providers. Consideration of these issues for improving
      the integration of service user participation in mental health care can help to
      inform integrated care within health care systems, broadly. This paper argues for
      practicing greater empathy and teaching it, stigma reduction, changing what we
      measure, valuing the intrinsic aspects of care more, employing more people with
      lived experience within mental health services, raising the visibility of service
      users as leaders and our teachers within services and redefining integrated care
      from the service user perspective. 

PMID- 25759609
TI  - Bone targeted therapy in breast cancer - an old concept but still much to do.

PMID- 25759607
TI  - Towards a taxonomy for integrated care: a mixed-methods study.
AB  - INTRODUCTION: Building integrated services in a primary care setting is
      considered an essential important strategy for establishing a high-quality and
      affordable health care system. The theoretical foundations of such integrated
      service models are described by the Rainbow Model of Integrated Care, which
      distinguishes six integration dimensions (clinical, professional, organisational,
      system, functional and normative integration). The aim of the present study is to
      refine the Rainbow Model of Integrated Care by developing a taxonomy that
      specifies the underlying key features of the six dimensions. METHODS: First, a
      literature review was conducted to identify features for achieving integrated
      service delivery. Second, a thematic analysis method was used to develop a
      taxonomy of key features organised into the dimensions of the Rainbow Model of
      Integrated Care. Finally, the appropriateness of the key features was tested in a
      Delphi study among Dutch experts. RESULTS: The taxonomy consists of 59 key
      features distributed across the six integration dimensions of the Rainbow Model
      of Integrated Care. Key features associated with the clinical, professional,
      organisational and normative dimensions were considered appropriate by the
      experts. Key features linked to the functional and system dimensions were
      considered less appropriate. DISCUSSION: This study contributes to the ongoing
      debate of defining the concept and typology of integrated care. This taxonomy
      provides a development agenda for establishing an accepted scientific framework
      of integrated care from an end-user, professional, managerial and policy
      perspective.

PMID- 25759610
TI  - Breast cancer and osteoporosis - management of cancer treatment-induced bone loss
      in postmenopausal women with breast cancer.
AB  - The incidence of breast cancer (BC) in postmenopausal women is continuously
      rising. Due to early diagnosis and various treatment designs, the long-term
      clinical outcome has improved. Frequent settings are chemotherapy as well as
      endocrine treatment. Both have proven to interfere with bone health resulting in
      cancer treatment-induced bone loss (CTIBL). Whereas chemotherapy is associated
      with increased bone resorption, aromatase inhibitor (AI) therapy reduces residual
      estrogen and is associated with decreased bone mineral density. Independent of
      the AI administered, the loss of bone mineral density is twice as high compared
      to healthy postmenopausal women. As a consequence of CTIBL, both chemotherapy and
      AI treatment can lead to a significantly increased fracture risk. Therefore,
      several guidelines have emerged for the management of CTIBL in women with BC,
      including strategies to identify and treat those at high risk for fractures.
      Further research on tracking guideline adherence examining the feasibility and
      practicability of guideline implementation to bridge the gap between determined
      scientific best evidence and applied best practice is needed to adjust these
      guidelines in the future. 

PMID- 25759611
TI  - Adjuvant bisphosphonates in breast cancer treatment.
AB  - Several solid tumors like breast cancer tend to spread to the bone, where the
      microenvironment is especially receptive to the tumor by special interactions
      between bone cells and tumor cells. Bone metastases often lead to skeletal
      related events with significant morbidity and mortality. The therapy of bone
      metastases and osteoporosis with bisphosphonates (BPs) has been established many
      years ago as a standard treatment. In the adjuvant setting, cancer treatment
      induced bone loss is a frequent cause of morbidity, and prevention and treatment
      of this condition with BPs and the monoclonal antibody denosumab are also well
      established. Besides postmenopausal patients, several studies including 2 larger
      studies by the Austrian Breast and Colorectal Cancer Study Group (ABCSG) and the
      Cancer and Leukemia Group B (CALGB) have shown an increase in bone mineral
      density in premenopausal women. BPs as anticancer treatment are, however, still
      controversial because several studies yielded conflicting results, with
      beneficial effects only in subgroups of patients. The publication of the latest
      Oxford overview of prospective trials is being awaited; at the presentation of
      the results, a 34% relative reduction of bone metastasis and a 17% improvement in
      overall survival was demonstrated in the subgroup of postmenopausal patients.
      These results will likely lead to an incorporation of the use of BPs into routine
      adjuvant breast cancer treatment. 

PMID- 25759612
TI  - Bone-targeted therapy in metastatic breast cancer - all well-established
      knowledge?
AB  - Bone-targeted therapies like bisphosphonates (zoledronic acid or pamidronate) or
      denosumab are recommended in all patients with metastatic breast cancer and bone
      metastases, whether they are symptomatic or not. The choice between these 2
      different agents, however, remains open. In this review, we critically discuss
      the emerging evidence for direct anti-tumor activity of bone-targeting agents,
      the utility of bone turnover markers for treatment decision and efficacy
      prediction, as well as the safety and financial aspects of bisphosphonates and
      denosumab. Furthermore, we provide a possible therapeutic algorithm, and present
      new pharmacologic agents which are being investigated for the treatment of
      metastatic bone disease. 

PMID- 25759613
TI  - Side effects of bone-targeted therapies in advanced breast cancer.
AB  - In up to 75% of cases, advanced breast cancer patients eventually develop bone
      metastases with often debilitating skeletal-related events (SREs). Osteoclast
      inhibitors are commonly used as therapeutic mainstay with clinical studies
      showing superiority of denosumab over bisphosphonates (e.g., zoledronate) for the
      prevention of SREs. The present review discusses the adverse event profile of
      these agents, and addresses the prevention and management of untoward side
      effects. Adverse events associated with osteoclast inhibitors comprise
      osteonecrosis of the jaw and hypocalcemia. Hypocalcemia is more common with
      denosumab, particularly in severe renal dysfunction. During therapy, the
      appropriate prevention of these adverse events includes close attention to dental
      health, avoidance of invasive dental procedures, supplementation with calcium and
      vitamin D unless patients are hypercalcemic, and regular monitoring of relevant
      serum values. Relating to the risk of nephrotoxicity, bisphosphonates but not
      denosumab have been incriminated. Therefore, serum creatinine levels should be
      checked prior to each dose of zoledronate, and in severe renal dysfunction
      (creatinine clearance < 30 ml/min) zoledronate is contraindicated anyway. Acute
      phase reactions are particularly linked to bisphosphonates. Consequently, if
      these adverse events predominate, switching to denosumab is recommended. 

PMID- 25759614
TI  - Can Steroids plus Surgery Become a First-Line Treatment of Idiopathic
      Granulomatous Mastitis?
AB  - BACKGROUND: The aim of this study is to compare the clinical course of idiopathic
      granulomatous mastitis (IGM) treated with low-dose oral corticosteroid therapy
      alone as opposed to treatment with low-dose corticosteroid therapy followed by
      surgery. PATIENTS AND METHODS: 37 patients were treated with an approach that
      consisted of methylprednisolone at a dose of 0.5 mg/kg/day followed by wide
      excision, and 23 patients were treated with an approach that consisted only of
      methylprednisolone. The treatment efficacy was compared between the two groups.
      RESULTS: Clinical and radiological regression was reported in all patients with
      steroid therapy, and the regression rate had a median of 75% (25-100%). No
      recurrence was observed in patients who were treated with wide surgical excision
      after steroid therapy during the median follow-up period of 38 (22-78) months.
      The control group of 23 patients was treated only with steroid therapy, and 7
      (30%) of these patients experienced recurrence in the follow-up period (p <
      0.001). CONCLUSIONS: Steroid therapy was effective in the treatment of IGM by
      reducing the lesion size and extent. With regard to the current treatment options
      available for IGM, surgical excision after steroid therapy seems the better
      treatment option compared to steroid therapy without surgical excision. This
      treatment sequence reduces the rate of recurrence.

PMID- 25759615
TI  - Taxanes Plus Trastuzumab Compared To Oral Vinorelbine Plus Trastuzumab in HER2
      Overexpressing Metastatic Breast Cancer.
AB  - BACKGROUND: This retrospective analysis was planned as a direct comparison of
      taxanes plus trastuzumab to the less toxic combination of oral vinorelbine (OV)
      plus trastuzumab as a first-line therapy for metastatic HER2-positive breast
      cancer. PATIENTS AND METHODS: Patients (n = 76) receiving either taxanes (group
      A) or OV (group B) in combination with trastuzumab were identified from a breast
      cancer database. Progression-free survival (PFS) was defined as the primary study
      endpoint; secondary endpoints were overall survival (OS), response rate (RR),
      incidence of brain metastases, and brain metastases-free survival (BMFS).
      RESULTS: 36 patients received taxanes and 40 patients OV in combination with
      trastuzumab. At a median follow-up of 47.5 months, median PFS was 7 months (group
      A) and 9 months in group B (log-rank; non-significant), respective numbers for OS
      were 49 and 59 months (p = 0.033). The incidence of brain metastases did not
      differ significantly between the 2 treatment groups, whereas BMFS was
      significantly longer in patients receiving OV. CONCLUSIONS: OV plus trastuzumab
      yielded similar results in terms of PFS and RR and was superior in terms of OS
      and BMFS. These results add to the growing body of evidence that vinorelbine is a
      viable alternative to taxanes in HER2-positive metastatic breast cancer.

PMID- 25759616
TI  - Guideline conformity treatment in young women with early-onset breast cancer in
      Germany.
AB  - BACKGROUND: The purpose of the study was to characterize the treatment of young
      mothers with breast cancer in Germany and to investigate whether it followed
      applicable guidelines. METHOD: Retrospective data obtained between 2002 and 2011
      for 1,053 mothers with children of < 12 years of age with adjuvantly treated loco
      regional primary breast cancer were analyzed. Collected data included
      sociodemographic data, TNM stage, biology of tumor and therapies. Actually
      received therapies were compared to those suggested in guideline treatment plans.
      RESULTS: The mean age of the patients was 39 years. 97% of the women with node
      positivity received an axillary dissection. Overall, 90% of the patients received
      chemotherapy with a guideline adherence range of 87-99% depending on clinical
      parameters. For radiation therapy, guideline adherence was high (range 82-100%).
      95% of the patients with a hormone receptor-positive tumor received endocrine
      therapy; in 94%, tamoxifen therapy was performed in compliance with guidelines,
      whereas gonadotropin-releasing hormone (GnRH) agonist therapy complied with the
      guidelines in 52% of the cases. CONCLUSION: Guideline adherence in young mothers
      with breast cancer in Germany was high (with the exception of GnRH therapy), as
      comorbidity or the ambiguity of the therapeutic success does not need to be
      considered as much in this young, otherwise usually healthy, cohort compared to
      an age-heterogeneous group.

PMID- 25759617
TI  - Pregnancy-associated breast cancer: clinicopathological characteristics of 20
      cases with a focus on identifiable causes of diagnostic delay.
AB  - BACKGROUND: The primary objective of this study was to evaluate the
      clinicopathological characteristics of patients with pregnancy-associated breast
      cancer (PABC), with a special focus on diagnostic delays and the identifiable
      causes of diagnostic delays. PATIENTS AND METHODS: Clinicopathological data of
      patients treated for PABC between 2003 and 2012 at Hacettepe University Hospital
      was retrospectively reviewed. RESULTS: 20 patients with PABC were included. The
      pathological examination revealed predominance of invasive ductal carcinoma
      (80%), grade III tumors (65%) and advanced-stage (III-IV) disease (75%). In 8
      patients (40%), there was a diagnostic delay between occurrence of the presenting
      symptoms and the initiation of breast mass workup. For these 8 patients, the main
      identifiable causes of diagnostic delay were the attribution of disease-related
      symptoms to pregnancy or lactation in 5 (63%) and negligence of symptoms in 2
      (25%). CONCLUSIONS: PABC mostly presents with advanced-stage disease, and there
      can be a substantial diagnostic delay before these patients receive treatment.
      Preconceptional, gestational and postpartum examination of women of reproductive
      age should include a thorough breast examination and should provide adequate
      information regarding the physiological changes in breast tissue and the possible
      pathological symptoms.

PMID- 25759618
TI  - Three Metachronous Cases of HER2-Positive Breast Cancer Accompanied with Thyroid
      Cancer.
AB  - BACKGROUND: Breast carcinoma (BC) and papillary thyroid carcinoma (PTC) occur
      predominantly in women. Many studies have shown that PTC is common among women
      with BC. Collision metastases in lymph nodes do occur but are not common. CASE
      REPORT: Here we report 3 metachronous cases of BC with PTC. PTC developed after
      BC in each case. Histology and immunohistochemistry revealed that HER2 status was
      positive in each BC, and in 1, concurrent metastases of BC and PTC were shown in
      a lymph node of the left cervical region. CONCLUSION: From our results, we
      speculate that women with HER2-positive breast cancer may be at a higher risk for
      thyroid cancer than other cancers. Finding 2 distinct types of cancer
      metastasized to 1 lymph node in a patient may, therefore, warrant a high index of
      suspicion and the use of immunohistochemical stains to differentiate the types of
      collision tumors.

PMID- 25759619
TI  - Options for breast cancer prevention in healthy women.

PMID- 25759620
TI  - Impact of Prophylactic Mastectomy in BRCA1/2 Mutation Carriers.
AB  - Unlike the general decrease in invasive oncologic care, the trend for
      prophylactic bilateral mastectomy in healthy women and prophylactic contralateral
      mastectomy in women with unilateral breast cancer is steadily rising. This is
      even more surprising when considering that for e.g. prophylactic contralateral
      mastectomy no clear survival benefit has been demonstrated so far. The decision
      making process around risk-reducing surgery may be influenced by several
      conflicting parameters such as the patient's fears and desire to achieve a
      survival advantage, the surgeon's financial motivations, or the oncologist's
      paternalistic approach to the above trend. Physicians should support their
      patients throughout the decision-making process, guide them through the dense fog
      of information, and encourage them to reconsider all options and alternatives
      before embarking on an irreversible surgical intervention. Healthy and diseased
      women should be comprehensively informed about their absolute individual risks
      for cancer, the benefits and harms of the surgery, alternative preventive
      strategies, and last but not least the competing risks of preceding carcinomas
      and cancer in general. Within the framework of non-directive counseling in the
      specialized centers of the German Consortium for Hereditary Breast and Ovarian
      Cancer (GC-HBOC), decision-making aids are being developed with grants from the
      Federal Ministry of Health and the German Cancer Aid to support women in making
      conclusive and satisfactory decisions. 

PMID- 25759621
TI  - Medical prevention of breast cancer.
AB  - Breast cancer is the most common cancer of women in Western Europe and North
      America. Effective strategies of medical prevention could reduce the burden of
      breast cancer mortality. The best evidence for a risk reduction exists for
      hormonal agents such as tamoxifen and raloxifene (22-72%) or aromatase inhibitors
      (50-65%). However, the severity of side effects and the lack of evidence for an
      improved survival compromise the risk/benefit balance. In this review the results
      of chemoprevention studies, including new treatment approaches, are summarized
      with critical discussion of their use in clinical practice. 

PMID- 25759622
TI  - Reproduction and breast cancer risk.
AB  - Reproduction is doubtlessly one of the main biological meanings of life. It is
      therefore not surprising that various aspects of reproduction impact on breast
      cancer risk. Various developmental levels may become targets of breast
      tumorigenesis. This review follows the chronologic sequence of events in the life
      of a female at risk, starting with the intrauterine development. Furthermore, the
      influence of both contraceptive measures and fertility treatment on breast cancer
      development is dealt with, as well as various pregnancy-associated factors,
      events, and perinatal outcomes. Finally, the contribution of breast feeding to a
      reduced breast cancer risk is discussed. 

PMID- 25759624
TI  - Wishes and beliefs of cancer patients regarding counseling on integrative
      medicine.
AB  - BACKGROUND: Today there is an agreement on how patients should be counseled
      regarding integrative medicine in oncology. In order to better meet the patients'
      demands, we investigated additional beliefs and wishes related to these topics.
      PATIENTS AND METHODS: Patients in 2 locations were asked to complete an
      assessment form regarding their wishes in relation to counseling on integrative
      medicine. RESULTS: Based on 404 returned assessment forms, we found that most
      patients wished to be counseled on integrative medicine by oncologists but also
      wanted to be treated by them with such methods. Oncologists received the best
      ratings regarding credibility, oncological competence, sympathy for patients, and
      honesty. Only with regard to time for patients did health practitioners receive
      better ratings. Physical exercise, balanced diets, and psycho-oncological support
      were the methods mainly recommended by physicians. Health practitioners mainly
      recommended taking mistletoe extracts, trace elements, and immunostimulants.
      CONCLUSION: It may be hypothesized from this work that the physicians' leading
      role in promoting integrative medicine in the field of oncology - which contrasts
      with findings in other countries - is perhaps based on the patients' desire to be
      treated and counseled by physicians, especially oncologists.

PMID- 25759623
TI  - Influence of lifestyle factors on breast cancer risk.
AB  - Breast Cancer (BC) is a life-changing event. Compared to other malignancies in
      women, BC has received considerably more public attention. Despite improved
      neoadjuvant, adjuvant, and palliative treatment strategies for each
      characteristic molecular BC subtype, recommendations for evidence-based
      preventive strategies for BC treatment are not given equivalent attention. This
      may be partly due to the fact that high-quality long-term prevention studies are
      still difficult to carry out and are thus underrepresented in international
      studies. The aim of this review is to discuss the most relevant lifestyle factors
      associated with BC and to identify and discuss the evidence supporting practical
      prevention strategies that can be used in everyday clinical practice. 

PMID- 25759625
TI  - Prognostic Factors in Operated Stage IIIC, Pathological N3a Breast Cancer
      Patients.
AB  - BACKGROUND: The aim of this retrospective study was to evaluate the prognostic
      factors in patients operated for stage IIIC breast carcinoma who had > 10
      positive axillary lymph nodes (pN3a). PATIENTS AND METHODS: The medical records
      of 302 operated N3a breast cancer patients without distant metastasis followed up
      in 2 medical oncology clinics in Ankara between January 1998 and June 2013 were
      evaluated retrospectively. RESULTS: The median age was 50 (21-83) years. The
      median follow-up time was 43 (5-191) months. The patients were divided into 4
      subgroups according to hormone receptor (HR) and human epidermal growth factor
      receptor 2 (HER2) status. There were 151 (50.0%) patients in the HR+/HER2- group,
      80 (26.5%) patients in the HR+/HER2+ group, 42 (13.9%) patients in the HR-/HER2+
      group, and 29 (9.6%) patients in the triple negative (TN) group. At the time of
      analysis, 155 (51.3%) patients had recurrent disease and 117 (38.7%) patients had
      died. The median disease-free survival (DFS) and overall survival (OS) times were
      46.0 and 78.0 months, respectively. Both the DFS and OS in the HR+/HER2- group
      were longer than in the other groups (log-rank p = 0.034 and p = 0.016,
      respectively). Menopausal status, progesterone receptor (PgR) status, and lymph
      node ratio (LNR; defined as the number of positive lymph nodes compared to the
      total number of removed lymph nodes) were found to be independent prognostic
      factors (p = 0.019, p = 0.001, and p = 0.012, respectively). CONCLUSION:
      Menopausal status, PgR status, and LNR were independent prognostic factors in
      operated N3a breast cancer patients, who are underrepresented in breast cancer
      trials.

PMID- 25759626
TI  - Lobular breast cancer metastasis to the colon, the appendix and the gallbladder.
AB  - BACKGROUND: Metastases of lobular breast cancer are commonly encountered at the
      level of lungs, bones, brain and liver, whereas lesions in the gastrointestinal
      tract are rarely seen. CASE REPORT: A case of a patient with metastases in the
      right colon and gallbladder originating from an invasive lobular carcinoma is
      described. CONCLUSION: Adequate diagnostic procedures should be performed in
      patients with a history of breast cancer and who show gastrointestinal symptoms
      to rule out the potential presence of gastrointestinal metastases.

PMID- 25759627
TI  - Local Breast Cancer Recurrence after Mastectomy and Breast-Conserving Surgery for
      Paget's Disease: A Meta-Analysis.
AB  - BACKGROUND: Paget's disease (PD) of the breast is a rare presentation of breast
      malignancy. Mastectomy has been considered the standard of care, but several
      studies have shown that breast-conserving surgery (BCS) with radiotherapy is an
      alternative option. According to the literature, the total recurrence rate is as
      high as 20-40%. In an effort to enable a rational therapy decision, we compiled
      and analyzed the available data on PD. METHODS: Pubmed, Web of Knowledge, and
      China Journal Net were searched for studies concerning treatment for PD between
      1990 and 2013. A meta-analysis was performed to compare the effect of different
      treatments. RESULTS: 7 studies with a total of 685 patients were included. The
      cumulative local recurrence rate was 7.6%, 5.6% among women undergoing mastectomy
      and 13.2% among those treated with BCS. Compared to the BCS group, mastectomy
      showed significant differences in terms of local recurrence (odds ratio = 0.38,
      95% confidence interval 0.21-0.69; p = 0.001). CONCLUSION: Since not all
      currently available diagnostic and therapeutic options (magnetic resonance
      imaging, radiotherapy, tamoxifen) were systematically used in the studies
      included in this meta-analysis, it may be presumptuous to suggest that mastectomy
      is the right choice for all patients with PD in a modern interdisciplinary
      setting. Rather we can conclude that all efforts should be undertaken to assure
      local control since BCS is not equivalent to mastectomy in the treatment of PD.

PMID- 25759628
TI  - Identification of a Novel 14q13.3 Deletion Involving the SLC25A21 Gene Associated
      with Familial Synpolydactyly.
AB  - Synpolydactyly is a relatively rare malformation. Recently, we came across a male
      infant with a familial synpolydactyly of the hands and feet. As most familial
      synpolydactyly syndromes have not been linked to any specific mutations, we felt
      further investigation was warranted. Using microarray and fluorescent in situ
      hybridization analysis, we identified a novel mutation of the SLC25A21 gene on
      chromosome 14. 

PMID- 25759629
TI  - Antepartum ornithine transcarbamylase deficiency.
AB  - Ornithine transcarbamylase deficiency (OTCD) is the most common type urea cycle
      enzyme deficiencies. This syndrome results from a deficiency of the mitochondrial
      enzyme ornithine transcarbamylase, which catalyzes the conversion of ornithine
      and carbamoyl phosphate to citrullin. Our case was a 28-year-old female diagnosed
      with OTCD following neurocognitive deficit during her first pregnancy. Although
      hyperammonemia was suspected as the cause of the patient's mental changes, there
      was no evidence of chronic liver disease. Plasma amino acid and urine organic
      acid analysis revealed OTCD. After combined modality treatment with arginine,
      sodium benzoate and hemodialysis, the patient's plasma ammonia level stabilized
      and her mental status returned to normal. At last she recovered without any
      damage left. 

PMID- 25759630
TI  - Zenker's Diverticulum: Diagnostic Approach and Surgical Management.
AB  - Zenker's diverticulum (ZD), also known as cricopharyngeal, pharyngoesophageal or
      hypopharyngeal diverticulum, is a rare condition characterized by an acquired
      outpouching of the mucosal and submucosal layers originating from the
      pharyngoesophageal junction. This false and pulsion diverticulum occurs dorsally
      at the pharyngoesophageal wall between the inferior pharyngeal constrictor and
      the cricopharyngeus muscle. The pathophysiology of ZD involves altered compliance
      of the cricopharyngeus muscle and raised intrabolus pressure. Decreased
      compliance of the upper esophageal sphincter and failure to open completely for
      effective bolus clearance both lead to an increase in the hypopharyngeal pressure
      gradient. Different open surgical techniques and transoral endoscopic approaches
      have been described for the management of ZD, although there is no consensus
      about the best option. We report the case of a 61-year-old patient with a 7-year
      history of dysphagia and odynophagia for solid food, which after 2 months
      progressed to dysphagia for liquids and after 4 months to regurgitation 2-6 h
      after meals. The patient experienced a 12-kg weight loss. Diagnosis was
      established by esophagogram, which showed a diverticulum through the posterior
      pharyngeal wall, suggestive of a ZD. Esophagogastroduodenoscopy showed a pouch
      with erythematous mucosa. Under general anesthesia, diverticulectomy and myotomy
      were performed. After an uneventful recovery and adequate oral intake, the
      patient remains free of symptoms at 4 months of follow-up. 

PMID- 25759631
TI  - Nitazoxanide Use as Part of an Empiric Multi-Drug Regimen in Treating Children
      with Suspected Helicobacter pylori Infection.
AB  - Helicobacter pylori, a Gram-negative bacterium found in the human stomach, is
      often present in patients with chronic gastritis. Traditional treatment for H.
      pylori infection includes metronidazole or clarithromycin, both being associated
      with development of resistance. In this retrospective report, we describe our
      clinical experience using a multi-drug treatment regimen for pediatric H. pylori
      that included nitazoxanide, a newer nitrothiazole benzamide compound used in
      treating intestinal protozoa infections. Charts were identified for patients who
      were treated between January 1, 2008 and December 31, 2013 with an ICD-9-CM code
      041.86 (H. pylori) and who underwent elective endoscopy. All patients were
      exposed to nitazoxanide for 3 days plus azithromycin, and cefixime (or another
      3rd-generation oral cephalosporin) for 7-10 days, plus a proton pump inhibitor
      for 30 days. The clinical cure criteria were predefined. There were 127
      individual occurrences or cases identified for inclusion in the review, with 111
      occurrences meeting the inclusion criteria. The success rate or clinical cure for
      the new therapy combination prescribed as defined prior to the chart review was
      99 out of 111 cases (89.2%). There were no serious adverse events observed or
      reported during the treatment of any patient. Approximately 10% of patient charts
      reflected minor complaints of nausea, vomiting or abdominal cramps during the
      time of active drug therapy. Nitazoxanide appears to be an effective and well
      tolerated option for use in combination with other agents to treat H. pylori
      induced gastritis. 

PMID- 25759632
TI  - Necrotizing encephalitis caused by disseminated Aspergillus infection after
      orthotopic liver transplantation.
AB  - Liver transplantation is the only available treatment for some patients with end
      stage liver disease. Despite reduction in mortality rates due to advances related
      to surgical techniques, intensive medical management and immunosuppressive
      therapy, invasive fungal infections remain a serious complication in orthotopic
      liver transplantation. We report the case of an 18-year-old male diagnosed with
      autoimmune cirrhosis in 2009 who was assessed and listed for liver
      transplantation for massive variceal hemorrhage. One year after listing a
      successful orthotopic liver transplantation was performed. Uneventful early
      recovery was achieved; however, he developed pulmonary and neurological
      Aspergillus infection 23 and 40 days after surgery, respectively. Antibiotic
      therapy with voriconazole and amphotericin was started early, with no major
      response. Neuroimaging revealed multiple right frontal and right parietal lesions
      with perilesional edema; surgical management of the brain abscesses was
      performed. A biopsy with periodic acid-Schiff and Gomori stains revealed areas
      with mycotic microorganisms morphologically consistent with Aspergillus, later
      confirmed by culture. The patient developed necrotizing encephalitis secondary to
      aspergillosis and died. Necrotizing encephalitis as a clinical presentation of
      Aspergillus infection in an orthotopic liver transplant is not common, and even
      with adequate management, early diagnosis and prompt antifungal treatment,
      mortality rates remain high. 

PMID- 25759633
TI  - Dysmetabolic hyperferritinemia: all iron overload is not hemochromatosis.
AB  - Disturbances in iron metabolism can be genetic or acquired and accordingly
      manifest as primary or secondary iron overload state. Organ damage may result
      from iron overload and manifest clinically as cirrhosis, diabetes mellitus,
      arthritis, endocrine abnormalities and cardiomyopathy. Hemochromatosis inherited
      as an autosomal recessive disorder is the most common genetic iron overload
      disorder. Expert societies recommend screening of asymptomatic and symptomatic
      individuals with hemochromatosis by obtaining transferrin saturation (calculated
      as serum iron/total iron binding capacity * 100). Further testing for the
      hemochromatosis gene is recommended if transferrin saturation is >45% with or
      without hyperferritinemia. However, management of individuals with low or normal
      transferrin saturation is not clear. In patients with features of iron overload
      and high serum ferritin levels, low or normal transferrin saturation should alert
      the physician to other - primary as well as secondary - causes of iron overload
      besides hemochromatosis. We present here a possible approach to patients with
      hyperferritinemia but normal transferrin saturation. 

PMID- 25759634
TI  - Laparoscopic resection of schwannoma of the ascending colon.
AB  - Schwannomas of the colon are rare and difficult to diagnose preoperatively. We
      report a case of schwannoma of the ascending colon that was resected
      laparoscopically. A 64-year-old woman was referred to our hospital by her local
      clinic for further evaluation and management of a submucosal tumor of the
      ascending colon. A definitive preoperative diagnosis could not be reached despite
      examinations. Gastrointestinal stromal tumor, leiomyoma and lymphoma were the
      differential diagnoses. We performed a laparoscopic right hemicolectomy with D2
      lymph node dissection. Histological findings with hematoxylin-eosin staining
      revealed spindle-like tumor cells, and immunohistochemical analysis showed that
      the tumor was positive for S-100 but negative for c-kit, CD34, smooth muscle
      actin and desmin, with a Ki-67 index of <5%. Thus, the diagnosis in this case was
      benign schwannoma of the ascending colon. 

PMID- 25759635
TI  - Inappropriate arginine vasopressin levels and hyponatremia associated with cyclic
      vomiting syndrome.
AB  - We herein describe two children who presented with attacks of severe cyclic
      vomiting. The primary case was a 2.5-year-old girl with a history of several
      admissions with vomiting and altered mental status. She was diagnosed with cyclic
      vomiting syndrome (CVS). During her attacks she developed significant
      hyponatremia on several occasions, which prompted us to measure plasma arginine
      vasopressin (AVP) levels during attacks. We found inappropriately high AVP levels
      with concomitant hyponatremia. We also measured plasma AVP and plasma sodium in
      another child with CVS who did not develop manifest hyponatremia but showed
      inappropriately elevated plasma AVP levels. Since the standard treatment of CVS
      consists of fluids, high plasma AVP levels may lead to dilutional hyponatremia.
      We would therefore like to emphasize the importance of close assessment of
      electrolyte levels in patients with CVS to avoid water intoxication. 

PMID- 25759636
TI  - Genetic manipulation of reptilian embryos: toward an understanding of cortical
      development and evolution.
AB  - The mammalian neocortex is a remarkable structure that is characterized by
      tangential surface expansion and six-layered lamination. However, how the
      mammalian neocortex emerged during evolution remains elusive. Because all modern
      reptiles have a homolog of the neocortex at the dorsal pallium, developmental
      analyses of the reptilian cortex are valuable to explore the origin of the
      neocortex. However, reptilian cortical development and the underlying molecular
      mechanisms remain unclear, mainly due to technical difficulties with sample
      collection and embryonic manipulation. Here, we introduce a method of embryonic
      manipulations for the Madagascar ground gecko and Chinese softshell turtle. We
      established in ovo electroporation and an ex ovo culture system to address neural
      stem cell dynamics, neuronal differentiation and migration. Applications of these
      techniques illuminate the developmental mechanisms underlying reptilian
      corticogenesis, which provides significant insight into the evolutionary steps of
      different types of cortex and the origin of the mammalian neocortex. 

PMID- 25759637
TI  - Spatiotemporal features for asynchronous event-based data.
AB  - Bio-inspired asynchronous event-based vision sensors are currently introducing a
      paradigm shift in visual information processing. These new sensors rely on a
      stimulus-driven principle of light acquisition similar to biological retinas.
      They are event-driven and fully asynchronous, thereby reducing redundancy and
      encoding exact times of input signal changes, leading to a very precise temporal
      resolution. Approaches for higher-level computer vision often rely on the
      reliable detection of features in visual frames, but similar definitions of
      features for the novel dynamic and event-based visual input representation of
      silicon retinas have so far been lacking. This article addresses the problem of
      learning and recognizing features for event-based vision sensors, which capture
      properties of truly spatiotemporal volumes of sparse visual event information. A
      novel computational architecture for learning and encoding spatiotemporal
      features is introduced based on a set of predictive recurrent reservoir networks,
      competing via winner-take-all selection. Features are learned in an unsupervised
      manner from real-world input recorded with event-based vision sensors. It is
      shown that the networks in the architecture learn distinct and task-specific
      dynamic visual features, and can predict their trajectories over time. 

PMID- 25759638
TI  - Impact of hypothalamic reactive oxygen species in the regulation of energy
      metabolism and food intake.
AB  - Hypothalamus is a key area involved in the control of metabolism and food intake
      via the integrations of numerous signals (hormones, neurotransmitters,
      metabolites) from various origins. These factors modify hypothalamic neurons
      activity and generate adequate molecular and behavioral responses to control
      energy balance. In this complex integrative system, a new concept has been
      developed in recent years, that includes reactive oxygen species (ROS) as a
      critical player in energy balance. ROS are known to act in many signaling
      pathways in different peripheral organs, but also in hypothalamus where they
      regulate food intake and metabolism by acting on different types of neurons,
      including proopiomelanocortin (POMC) and agouti-related protein
      (AgRP)/neuropeptide Y (NPY) neurons. Hypothalamic ROS release is under the
      influence of different factors such as pancreatic and gut hormones, adipokines
      (leptin, apelin,...), neurotransmitters and nutrients (glucose, lipids,...). The
      sources of ROS production are multiple including NADPH oxidase, but also the
      mitochondria which is considered as the main ROS producer in the brain. ROS are
      considered as signaling molecules, but conversely impairment of this neuronal
      signaling ROS pathway contributes to alterations of autonomic nervous system and
      neuroendocrine function, leading to metabolic diseases such as obesity and type 2
      diabetes. In this review we focus our attention on factors that are able to
      modulate hypothalamic ROS release in order to control food intake and energy
      metabolism, and whose deregulations could participate to the development of
      pathological conditions. This novel insight reveals an original mechanism in the
      hypothalamus that controls energy balance and identify hypothalamic ROS signaling
      as a potential therapeutic strategy to treat metabolic disorders. 

PMID- 25759639
TI  - HDAC4 as a potential therapeutic target in neurodegenerative diseases: a summary
      of recent achievements.
AB  - For the past decade protein acetylation has been shown to be a crucial post
      transcriptional modification involved in the regulation of protein functions.
      Histone acetyltransferases (HATs) mediate acetylation of histones which results
      in the nucleosomal relaxation associated with gene expression. The reverse
      reaction, histone deacetylation, is mediated by histone deacetylases (HDACs)
      leading to chromatin condensation followed by transcriptional repression. HDACs
      are divided into distinct classes: I, IIa, IIb, III, and IV, on the basis of size
      and sequence homology, as well as formation of distinct repressor complexes.
      Implications of HDACs in many diseases, such as cancer, heart failure, and
      neurodegeneration, have identified these molecules as unique and attractive
      therapeutic targets. The emergence of HDAC4 among the members of class IIa family
      as a major player in synaptic plasticity raises important questions about its
      functions in the brain. The characterization of HDAC4 specific substrates and
      molecular partners in the brain will not only provide a better understanding of
      HDAC4 biological functions but also might help to develop new therapeutic
      strategies to target numerous malignancies. In this review we highlight and
      summarize recent achievements in understanding the biological role of HDAC4 in
      neurodegenerative processes. 

PMID- 25759640
TI  - Action potential processing in a detailed Purkinje cell model reveals a critical
      role for axonal compartmentalization.
AB  - The Purkinje cell (PC) is among the most complex neurons in the brain and plays a
      critical role for cerebellar functioning. PCs operate as fast pacemakers
      modulated by synaptic inputs but can switch from simple spikes to complex bursts
      and, in some conditions, show bistability. In contrast to original works
      emphasizing dendritic Ca-dependent mechanisms, recent experiments have supported
      a primary role for axonal Na-dependent processing, which could effectively
      regulate spike generation and transmission to deep cerebellar nuclei (DCN). In
      order to account for the numerous ionic mechanisms involved (at present including
      Nav1.6, Cav2.1, Cav3.1, Cav3.2, Cav3.3, Kv1.1, Kv1.5, Kv3.3, Kv3.4, Kv4.3,
      KCa1.1, KCa2.2, KCa3.1, Kir2.x, HCN1), we have elaborated a multicompartmental
      model incorporating available knowledge on localization and gating of PC ionic
      channels. The axon, including initial segment (AIS) and Ranvier nodes (RNs),
      proved critical to obtain appropriate pacemaking and firing frequency modulation.
      Simple spikes initiated in the AIS and protracted discharges were stabilized in
      the soma through Na-dependent mechanisms, while somato-dendritic Ca channels
      contributed to sustain pacemaking and to generate complex bursting at high
      discharge regimes. Bistability occurred only following Na and Ca channel down
      regulation. In addition, specific properties in RNs K currents were required to
      limit spike transmission frequency along the axon. The model showed how organized
      electroresponsive functions could emerge from the molecular complexity of PCs and
      showed that the axon is fundamental to complement ionic channel
      compartmentalization enabling action potential processing and transmission of
      specific spike patterns to DCN. 

PMID- 25759641
TI  - Scalable and DiI-compatible optical clearance of the mammalian brain.
AB  - Efficient optical clearance is fundamental for whole brain imaging. In
      particular, clearance of the brain without membrane damage is required for the
      imaging of lipophilic tracer-labeled neural tracts. Relying on an ascending
      gradient of fructose solutions, SeeDB can achieve sufficient transparency of the
      mouse brain while ensuring that the plasma membrane remains intact. However, it
      is challenging to extend this method to larger mammalian brains due to the
      extremely high viscosity of the saturated fructose solution. Here we report a
      SeeDB-derived optical clearing method, termed FRUIT, which utilizes a cocktail of
      fructose and urea. As demonstrated in the adult mouse brain, combination of these
      two highly water-soluble clearing agents exerts a synergistic effect on
      clearance. More importantly, the final FRUIT solution has low viscosity so as to
      produce transparency of the whole adult rabbit brain via arterial perfusion,
      which is impossible to achieve with a saturated fructose solution. In addition to
      good compatibility with enhanced yellow fluorescent protein, the cocktail also
      preserves the fluorescence of the lipophilic tracer DiI. This work provides a
      volume-independent optical clearing method which retains the advantages of SeeDB,
      particularly compatibility with lipophilic tracers. 

PMID- 25759642
TI  - Dissociation of retinal and headcentric disparity signals in dorsal human cortex.
AB  - Recent fMRI studies have shown fusion of visual motion and disparity signals for
      shape perception (Ban et al., 2012), and unmasking camouflaged surfaces (Rokers
      et al., 2009), but no such interaction is known for typical dorsal motion pathway
      tasks, like grasping and navigation. Here, we investigate human speed perception
      of forward motion and its representation in the human motion network. We observe
      strong interaction in medial (V3ab, V6) and lateral motion areas (MT(+)), which
      differ significantly. Whereas the retinal disparity dominates the binocular
      contribution to the BOLD activity in the anterior part of area MT(+), headcentric
      disparity modulation of the BOLD response dominates in area V3ab and V6. This
      suggests that medial motion areas not only represent rotational speed of the head
      (Arnoldussen et al., 2011), but also translational speed of the head relative to
      the scene. Interestingly, a strong response to vergence eye movements was found
      in area V1, which showed a dependency on visual direction, just like vertical
      size disparity. This is the first report of a vertical-size disparity correlate
      in human striate cortex. 

PMID- 25759643
TI  - Neuronal correlates of social decision making are influenced by social value
      orientation-an fMRI study.
AB  - Our decisions often have consequences for other people. Hence, self-interest and
      other-regarding motives are traded off in many daily-life situations.
      Interindividually, people differ in their tendency to behave prosocial. These
      differences are captured by the concept of social value orientation (SVO), which
      assumes stable, trait-like tendencies to act selfish or prosocial. This study
      investigates group differences in prosocial decision making and addresses the
      question of whether prosocial individuals act intuitively and selfish individuals
      instead need to control egoistic impulses to behave prosocially. We address this
      question via the interpretation of neuronal and behavioral indicators. In the
      present fMRI-study participants were grouped into prosocial- and selfish
      participants. They made decisions in multiple modified Dictator-Games (DG) that
      addressed self- and other-regarding motives to a varying extent (self gain, non
      costly social gain, mutual gain, costly social gain). Selfish participants
      reacted faster than prosocial participants in all conditions, except for
      decisions in the non-costly social condition, in which selfish participants
      displayed the longest decision times. In the total sample we found enhanced
      neural activity in the ventromedial prefrontal cortex (vmPFC) and dorsomedial
      prefrontal cortex (dmPFC/BA 9) during decisions that resulted in non-costly
      social benefits. These areas have been implicated in cognitive control processes
      and deliberative value integration. Decisively, these effects were stronger in
      the group of selfish individuals. We believe that selfish individuals require
      more explicit and deliberative processing during prosocial decisions. Our results
      are compatible with the assumption that prosocial decisions in prosocials are
      more intuitive, whereas they demand more active reflection in selfish
      individuals. 

PMID- 25759644
TI  - Impaired top-down modulation of saccadic latencies in patients with schizophrenia
      but not in first-degree relatives.
AB  - Impaired eye movements have a long history in schizophrenia research and meet the
      criteria of a reliable biomarker. However, the effects of cognitive load and task
      difficulty on saccadic latencies (SL) are less understood. Recent studies showed
      that SL are strongly task dependent: SL are decreased in tasks with higher
      cognitive demand, and increased in tasks with lower cognitive demand. The present
      study investigates SL modulation in patients with schizophrenia and their first
      degree relatives. A group of 13 patients suffering from ICD-10 schizophrenia, 10
      first-degree relatives, and 24 control subjects performed two different types of
      visual tasks: a color task and a Landolt ring orientation task. We used video
      based oculography to measure SL. We found that patients exhibited a similar
      unspecific SL pattern in the two different tasks, whereas controls and relatives
      exhibited 20-26% shorter average latencies in the orientation task (higher
      cognitive demand) compared to the color task (lower cognitive demand). Also,
      classification performance using support vector machines suggests that relatives
      should be assigned to the healthy controls and not to the patient group.
      Therefore, visual processing of different content does not modulate SL in
      patients with schizophrenia, but modulates SL in the relatives and healthy
      controls. The results reflect a specific oculomotor attentional dysfunction in
      patients with schizophrenia that is a potential state marker, possibly caused by
      impaired top-down disinhibition of the superior colliculus by frontal/prefrontal
      areas such as the frontal eye fields. 

PMID- 25759645
TI  - Modulation of anxiety by cortical serotonin 1A receptors.
AB  - Serotonin (5-HT) plays an important role in the modulation of behavior across
      animal species. The serotonin 1A receptor (Htr1a) is an inhibitory G-protein
      coupled receptor that is expressed both on serotonin and non-serotonin neurons in
      mammals. Mice lacking Htr1a show increased anxiety behavior suggesting that its
      activation by serotonin has an anxiolytic effect. This outcome can be mediated by
      either Htr1a population present on serotonin (auto-receptor) or non-serotonin
      neurons (hetero-receptor), or both. In addition, both transgenic and
      pharmacological studies have shown that serotonin acts on Htr1a during
      development to modulate anxiety in adulthood, demonstrating a function for this
      receptor in the maturation of anxiety circuits in the brain. However, previous
      studies have been equivocal about which Htr1a population modulates anxiety
      behavior, with some studies showing a role of Htr1a hetero-receptor and others
      implicating the auto-receptor. In particular, cell-type specific rescue and
      suppression of Htr1a expression in either forebrain principal neurons or
      brainstem serotonin neurons reached opposite conclusions about the role of the
      two populations in the anxiety phenotype of the knockout. One interpretation of
      these apparently contradictory findings is that the modulating role of these two
      populations depends on each other. Here we use a novel Cre-dependent inducible
      allele of Htr1a in mice to show that expression of Htr1a in cortical principal
      neurons is sufficient to modulate anxiety. Together with previous findings, these
      results support a hetero/auto-receptor interaction model for Htr1a function in
      anxiety. 

PMID- 25759646
TI  - The development of trunk control and its relation to reaching in infancy: a
      longitudinal study.
AB  - The development of reaching is crucially dependent on the progressive control of
      the trunk, yet their interrelation has not been addressed in detail. Previous
      studies on seated reaching evaluated infants during fully supported or
      unsupported conditions; however, trunk control is progressively developed,
      starting from the cervical/thoracic followed by the lumbar/pelvic regions for the
      acquisition of independent sitting. Providing external trunk support at different
      levels to test the effects of controlling the upper and lower regions of the
      trunk on reaching provides insight into the mechanisms by which trunk control
      impacts reaching in infants. Ten healthy infants were recruited at 2.5 months of
      age and tested longitudinally, until 8 months. During the reaching test, infants
      were placed in an upright seated position and an adjustable support device
      provided trunk fixation at pelvic and thoracic levels. Kinematic and
      electromyographic data were collected. Results showed that prior to independent
      sitting, postural instability was higher when infants were provided with pelvic
      compared to thoracic support. Associated reaches were more circuitous, less
      smooth and less efficient. In response to the instability, there was increased
      postural muscle activity and arm muscle co-activation. Differences between levels
      of support were not observed once infants acquired independent sitting. These
      results suggest that trunk control is acquired in a segmental sequence across the
      development of upright sitting, and it is tightly correlated with reaching
      performance. 

PMID- 25759647
TI  - Electrocorticographic representations of segmental features in continuous speech.
AB  - Acoustic speech output results from coordinated articulation of dozens of
      muscles, bones and cartilages of the vocal mechanism. While we commonly take the
      fluency and speed of our speech productions for granted, the neural mechanisms
      facilitating the requisite muscular control are not completely understood.
      Previous neuroimaging and electrophysiology studies of speech sensorimotor
      control has typically concentrated on speech sounds (i.e., phonemes, syllables
      and words) in isolation; sentence-length investigations have largely been used to
      inform coincident linguistic processing. In this study, we examined the neural
      representations of segmental features (place and manner of articulation, and
      voicing status) in the context of fluent, continuous speech production. We used
      recordings from the cortical surface [electrocorticography (ECoG)] to
      simultaneously evaluate the spatial topography and temporal dynamics of the
      neural correlates of speech articulation that may mediate the generation of
      hypothesized gestural or articulatory scores. We found that the representation of
      place of articulation involved broad networks of brain regions during all phases
      of speech production: preparation, execution and monitoring. In contrast, manner
      of articulation and voicing status were dominated by auditory cortical responses
      after speech had been initiated. These results provide a new insight into the
      articulatory and auditory processes underlying speech production in terms of
      their motor requirements and acoustic correlates. 

PMID- 25759648
TI  - Corrigendum: Correlated activity supports efficient cortical processing.
AB  - [This corrects the article on p. 171 in vol. 8, PMID: 25610392.]. 

PMID- 25759649
TI  - Network dynamics with BrainX(3): a large-scale simulation of the human brain
      network with real-time interaction.
AB  - BrainX(3) is a large-scale simulation of human brain activity with real-time
      interaction, rendered in 3D in a virtual reality environment, which combines
      computational power with human intuition for the exploration and analysis of
      complex dynamical networks. We ground this simulation on structural connectivity
      obtained from diffusion spectrum imaging data and model it on neuronal population
      dynamics. Users can interact with BrainX(3) in real-time by perturbing brain
      regions with transient stimulations to observe reverberating network activity,
      simulate lesion dynamics or implement network analysis functions from a library
      of graph theoretic measures. BrainX(3) can thus be used as a novel immersive
      platform for exploration and analysis of dynamical activity patterns in brain
      networks, both at rest or in a task-related state, for discovery of signaling
      pathways associated to brain function and/or dysfunction and as a tool for
      virtual neurosurgery. Our results demonstrate these functionalities and shed
      insight on the dynamics of the resting-state attractor. Specifically, we found
      that a noisy network seems to favor a low firing attractor state. We also found
      that the dynamics of a noisy network is less resilient to lesions. Our
      simulations on TMS perturbations show that even though TMS inhibits most of the
      network, it also sparsely excites a few regions. This is presumably due to anti
      correlations in the dynamics and suggests that even a lesioned network can show
      sparsely distributed increased activity compared to healthy resting-state, over
      specific brain areas. 

PMID- 25759650
TI  - Merkel Cell Carcinoma Concomitant with Invasive Bowen's Disease:
      Immunohistochemical Investigation of Tumor-Infiltrating Leukocytes.
AB  - Merkel cell carcinoma (MCC) is an aggressive, cutaneous, neuroendocrine carcinoma
      and, in rare cases, occurs with Bowen's disease (BD). In this report, we describe
      a case of MCC concurrent with invasive BD and compare the profiles of tumor
      infiltrating leukocytes in the lesional skin of MCC and invasive BD.
      Interestingly, immunohistochemical study revealed significant numbers of CD8+
      cells and caspase 3-expressing cells in the same areas of invasive BD and MCC.
      Our present case suggests that MCC concurrent with invasive BD might have a good
      prognosis because of the substantial number of CD8+ cells in the tumor. 

PMID- 25759651
TI  - A plaque-type solitary reticulohistiocytoma in a two-year-old boy.
AB  - Reticulohistiocytoma (RH) is a dermal histiocytic infiltration composed of large
      histiocytes with eosinophilic glassy cytoplasm. RH is classified into three
      clinical forms: solitary RH, diffuse cutaneous RH without systemic involvement
      and multicentric reticulohistiocytosis with systemic diseases. Solitary RH
      generally manifests as a nodular lesion in adults without accompanying systemic
      diseases. Herein, we describe a case of solitary RH with an atypical clinical
      manifestation as a red-brown-colored plaque in a 2-year-old boy. Atypical
      presentations of RH may pose diagnostic difficulty unless RH is considered. A
      correct diagnosis of RH can ensure avoidance of unnecessary invasive procedures. 

PMID- 25759652
TI  - A Case of Cellular Fibrous Histiocytoma on the Right Elbow with Repeated Relapse
      within a Short Period.
AB  - Cellular fibrous histiocytoma, a variant of fibrous histiocytoma, is a
      designation used for lesions showing increased cellularity with a fascicular
      growth pattern and frequent extension into the subcutis. Here we describe a case
      of cellular fibrous histiocytoma showing repeated recurrence in a 36-year-old
      woman who initially presented with a 2-cm cutaneous tumor on her right elbow.
      Histopathologically, the first resected specimen demonstrated irregularly
      arranged collagen fibers mixed with scattered proliferating plump to spindle
      shaped fibrohistiocytes. However, examination of the resected specimens obtained
      after recurrence showed that the cellularity had increased, the spindle-shaped
      cells showing monomorphic proliferation with a fascicular and storiform growth
      pattern extending into the subcutis, as well as an increase of Ki-67 positivity.
      Since the lesion showed repeated relapse within a short period, we performed wide
      field resection of the tumor with a 3-cm margin. Currently, 48 months after
      surgery, there has been no local recurrence or metastasis, but continuous strict
      follow-up will be necessary. 

PMID- 25759653
TI  - Acinic cell carcinoma of the parotid gland: a case report and review of the
      literature.
AB  - We report on a patient who was referred to the ENT service following an
      incidental finding on an MRI scan of the brain. It revealed a mass in the right
      parapharyngeal space, and additional imaging confirmed the presence of a solid
      cystic expansive mass with moderate enhancement following contrast media
      injection. The patient was treated with a total parotidectomy followed by
      radiotherapy. Currently, the patient is disease-free without any complications. 

PMID- 25759654
TI  - A case of post-radiotherapy gastritis: radiation does not explain everything.
AB  - Hemorrhagic gastritis is a possible late toxicity outcome after radical
      radiotherapy but it is nowadays a very rare condition and most likely depends on
      other clinical factors. We report the case of a 77-year-old woman with a
      symptomatic solitary extramedullary intra-abdominal plasmacytoma and multiple
      gastric comorbidities, treated with external beam radiotherapy. Despite the good
      response to radiotherapy, the patient experienced multiple gastric bleeding a few
      months later, with the need of multiple treatments for its control. In this paper
      we will discuss in detail all aspects related to the different causes of
      hemorrhagic gastritis. 

PMID- 25759655
TI  - External beam radiotherapy for focal lymphoepithelioma-like carcinoma in the
      urinary bladder: a case report and literature review.
AB  - Lymphoepithelioma is a malignant epithelial tumor in the nasopharynx
      characterized by prominent lymphoid infiltration. Carcinomas that resemble
      lymphoepitheliomas have been called lymphoepithelioma-like carcinomas and have
      been reported in other organs. A tumor in the bladder is categorized by the
      percentage of the total area occupied by the lymphoepithelioma-like carcinoma
      pattern, with the prognosis dependent on the percentage. We present an 81-year
      old man with stage 3 chronic obstructive pulmonary disease and a history of
      aortic aneurysm repair. The computed tomography scans indicated thickening and
      irregularity of the bladder wall, with left external iliac lymph node metastasis.
      His diagnosis was bladder cancer, and the clinical stage was evaluated as T3N1M0.
      Transurethral resection of the bladder tumor was performed, and the pathological
      specimen showed that the tumor was composed of undifferentiated malignant cells
      with sheets and nests arranged in a syncytial pattern, as well as an urothelial
      carcinoma lesion. A prominent lymphoid reaction accompanied the tumor. The
      pathological diagnosis was focal-type lymphoepithelioma-like carcinoma containing
      a component of urothelial carcinoma G3>G2. His general condition was such that he
      could not tolerate radical cystectomy or systemic chemotherapy. External beam
      radiotherapy (total 60 Gy) was given to the bladder, including the lymph node
      metastatic lesion. No cancer recurrence was detected by regular follow-up
      computed tomography and cystoscopy. He eventually died of other causes 48 months
      later. Although treatment for focal lymphoepithelioma-like carcinoma generally
      requires multifocal therapies, in the present case, the bladder became tumor
      free. We also summarize previously reported lymphoepithelioma-like carcinoma
      cases treated with radiotherapy. 

PMID- 25759656
TI  - A case of orbital metastasis as disease progression of anaplastic lymphoma kinase
      positive lung cancer treated with crizotinib.
AB  - Orbital metastasis of lung cancer is rare. It often causes visual disorder. To
      date, there are only a few case reports. Crizotinib is an anaplastic lymphoma
      kinase (ALK) tyrosine kinase inhibitor that leads to responses in most patients
      with ALK-positive non-small-cell lung cancer. Visual disorder is one of the
      popular adverse events of crizotinib, but the symptom almost decreases over time.
      We report a case of orbital metastasis as the disease progression of ALK-positive
      lung cancer treated with crizotinib. It should be kept in mind that orbital
      metastasis can be the disease progression of lung adenocarcinoma with ALK
      translocation treated with crizotinib. When physicians encounter a patient
      receiving crizotinib with visual disorder, we must distinguish between adverse
      events and orbital metastasis. 

PMID- 25759657
TI  - A patient-invented maneuver to alleviate freezing of gait using a foot loop band.
AB  - Freezing of gait (FOG) is a disabling gait disorder in parkinsonian patients
      characterized by the inability to initiate or continue locomotion. I herein
      present a 65-year-old man with Parkinson's disease who invented a unique method
      (foot loop band) to alleviate FOG, which has not been previously described in the
      literature. The mechanisms to alleviate FOG include not only facilitating
      mechanical weight shift, but also restoring internal cueing and driving motor
      commands for gait initiation. This patient-invented maneuver may be recommended
      for patients having intractable FOG, because it is portable, cheap and safe. 

PMID- 25759658
TI  - Brain Abscess due to Staphylococcus lugdunensis in the Absence of Endocarditis or
      Bacteremia.
AB  - Staphylococcus lugdunensis has been recognized to be a microorganism potentially
      more virulent than other coagulase-negative staphylococci. We report the case of
      a patient who presented with a single, large, right, frontoparietal abscess that
      evolved despite conventional antibiotic treatment. Bacteremia and endocarditis
      were excluded. After surgical treatment, S. lugdunensis sensible to trimethoprim
      sulfamethoxazole was isolated, and the patient responded favorably to treatment.
      Although the ability of S. lugdunensis to produce brain abscesses has been
      recognized, we report a case of a brain abscess in the absence of bacteremia or
      endocarditis. 

PMID- 25759659
TI  - Chronic subdural hematoma infected by propionibacterium acnes: a case report.
AB  - We present a very rare case of a patient with an infected subdural hematoma due
      to Propionibacterium acnes. A 63-year-old male complained of dizziness and was
      admitted to our hospital. He had a history of left chronic subdural hematoma due
      to a traffic accident, which had been conservatively treated. Physical,
      neurological and laboratory examinations revealed no definite abnormality. Plain
      CT scan demonstrated a hypodense crescentic fluid collection over the surface of
      the left cerebral hemisphere. The patient was diagnosed with chronic subdural
      hematoma and underwent burr hole surgery three times and selective embolization
      of the middle meningeal artery, but the lesion easily recurred. Repeated culture
      examinations of white sedimentation detected P. acnes. Therefore, he underwent
      craniotomy surgery followed by intravenous administration of antibiotics. The
      infected subdural hematoma was covered with a thick, yellowish outer membrane,
      and the large volume of pus and hematoma was removed. However, the lesion
      recurred again and a low-density area developed in the left frontal lobe.
      Craniotomy surgery was performed a second time, and two Penrose drainages were
      put in both the epidural and subdural spaces. Subsequently, the lesions
      completely resolved and he was discharged without any neurological deficits.
      Infected subdural hematoma may be refractory to burr hole surgery or craniotomy
      alone, in which case aggressive treatment with craniotomy and continuous drainage
      should be indicated before the brain parenchyma suffers irreversible damage. 

PMID- 25759660
TI  - Type 1 idiopathic macular telangiectasia associated with type 3
      neovascularization.
AB  - PURPOSE: To report the case of a patient with unilateral idiopathic macular
      telangiectasia (IMT) associated with type 3 neovascularization. METHODS:
      Observational case report. RESULTS: We describe a case of an 85-year-old woman
      who presented at our department with a gradual vision loss in her left eye (LE).
      Her best-corrected visual acuity (BCVA) was 20/200 in the LE. Fundus examination
      showed 2 small hemorrhages located nasally to the LE fovea, as well as lipid
      exudates. Fluorescein angiography revealed early hyperfluorescence corresponding
      to the dilated capillaries. Spectral-domain optical coherence tomography (SD-OCT)
      showed several microaneurysms within the inner retinal layers. Late indocyanine
      green angiography revealed a focal hyperfluorescence corresponding to a type 3
      neovascularization. No signs of IMT or type 3 neovascularization were detected in
      the right eye. Based on these findings, the patient was diagnosed with type 1 IMT
      and coincident type 3 neovascularization. The LE was treated with intravitreal
      anti-vascular endothelial growth factor (anti-VEGF) injections. Twenty-four
      months later, SD-OCT revealed regression of the exudative signs, and LE BCVA
      improved to 20/100. CONCLUSION: We describe the case of an unusual association
      between older-onset IMT and type 3 neovascularization, and subsequent regression
      by anti-VEGF injections. We propose a new IMT subtype called type 1C for this
      association. Further research must be done in order to establish the
      pathophysiologic mechanism and likelihood of this association.

PMID- 25759661
TI  - Blowout Fracture after Descemet's Stripping Automated Endothelial Keratoplasty.
AB  - We present the case of an 86-year-old woman who developed a blowout fracture
      after Descemet's stripping automated endothelial keratoplasty (DSAEK). Sixteen
      months after DSAEK, she suffered a blow to her left eye caused by a fall.
      Computed tomography confirmed the presence of a blowout fracture of the inferior
      wall of the left orbit with soft tissue prolapsing into the orbit. The patient
      complained of no abnormal symptoms, and her operated cornea was intact and clear.
      There was no abnormal finding in both the anterior and posterior segments. This
      case highlights that the DSAEK technique provides adequate tectonic stability of
      the globe throughout the traumatic event in contrast to penetrating keratoplasty,
      which can lead to devastating vision damage after trauma. 

PMID- 25759662
TI  - A case of vogt-koyanagi-harada syndrome with persistent dyspnea secondary to
      laryngeal edema.
AB  - PURPOSE: We report a case of laryngeal edema associated with the Vogt-Koyanagi
      Harada (VKH) syndrome. PATIENT AND METHODS: A 32-year-old African-American female
      presented with a 12-day prodrome, including headache, tinnitus and shortness of
      breath, which preceded sudden photophobia and bilateral visual loss. Examination
      and clinical testing were most consistent with VKH, and the patient improved with
      intravenous methylprednisolone therapy. RESULTS: The patient had persistent
      dyspnea, which was out of proportion to chest CT findings and which was
      exacerbated during a recurrence of VKH. Flexible fiberoptic laryngoscopy with
      stroboscopy revealed diffuse laryngeal edema. Symptoms were alleviated with
      breathing exercises. CONCLUSIONS: Several autoimmune diseases may cause diffuse
      laryngeal edema. In this case, VKH was associated with the patient's glottic
      edema and dyspnea. We recommend that laryngeal edema be considered in the
      differential diagnosis for patients with dyspnea and VKH.

PMID- 25759663
TI  - A novel case of superior rectus injury and its subsequent surgery.
AB  - We report a presumed damage to the left superior rectus (SR) muscle following a
      dog bite injury that resulted in a marked weakness of elevation and vertical
      diplopia. A 30-year-old male presented in October 2010 following a dog bite
      around his left superotemporal orbit. An ophthalmic examination was unremarkable.
      The patient immediately complained of vertical diplopia, which did not settle
      during a period of observation lasting approximately 9 months following the
      attack. An orthoptist examination confirmed a marked restriction of upgaze. A
      diagnosis of isolated SR injury, secondary to the dog bite, was suspected. A left
      Knapp procedure was performed. The surgery was uneventful with scar tissue found
      around the SR. Three months following his surgery, the patient was orthophoric in
      both primary positions and in the downgaze with a residual 20-prism dioptre
      hypotropia in the upgaze. Our patient was unusual in that the bite weakened the
      SR in isolation. We also show the successful management of this novel case using
      a simple Knapp procedure. 

PMID- 25759664
TI  - Visually evoked potentials in a patient with a fyodorov-zuev keratoprosthesis.
AB  - PURPOSE: To describe a visually evoked potential (VEP) examination performed on a
      patient with a keratoprosthesis. METHODS: We report the case of a 60-year-old
      patient with a Fyodorov-Zuev keratoprosthesis in the right eye complained of
      gradual visual deterioration in that eye. His past medical history consisted of
      failed corneal graft procedures due to corneal dystrophy and an Ahmed valve
      implantation due to secondary glaucoma. A clinical examination and an ultrasound
      demonstrated vitreal opacities. In order to assess the visual status, a flash VEP
      test was conducted. RESULTS: VEP recorded from the right eye consisted of a
      broadened and poorly formed positive P1 wave, with a subnormal amplitude, but a
      normal latency. Consequently, the patient underwent a pars plana vitrectomy.
      CONCLUSION: This case demonstrates the viability of VEP exams in patients with
      keratoprostheses.

PMID- 25759665
TI  - Choroidal neovascularization induced by immunogenic alteration of the retinal
      pigment epithelium in dengue Fever.
AB  - PURPOSE: To report the first case of choroidal neovascularization (CNV) secondary
      to dengue fever. CASE REPORT: A 54-year-old female was referred to our department
      with blurred vision and metamorphopsia in her left eye. Two weeks earlier, she
      had presented all of the classic symptoms of dengue fever including a positive
      serology. Her best-corrected visual acuity (BCVA) was 20/150 in the left eye. She
      underwent a fundus examination, fluorescein angiography (FA) and spectral domain
      optical coherence tomography. RESULTS: All findings were consistent with CNV
      secondary to dengue fever. FA revealed a classic CNV associated with focal
      retinal pigment epithelium (RPE) destruction and detachment. Three consecutive
      monthly injections of intravitreal ranibizumab resulted in functional and
      anatomical improvement for as long as 6 months with a BCVA of 20/25. However, CNV
      recurred 2 years later, again with an improvement after ranibizumab therapy, but
      with persistence of a fibrovascular RPE detachment, highlighting the
      pathomechanism of a classic CNV formation. CONCLUSIONS: Maculopathy in dengue
      fever may be followed by CNV as a result of the immunologic alteration of the
      RPE. Physicians should be aware of this manifestation to be able to initiate
      adequate treatment with excellent functional and anatomical results.

PMID- 25759666
TI  - Ophthalmic manifestations of vitamin A and D deficiency in two autistic
      teenagers: case reports and a review of the literature.
AB  - We describe the cases of 2 autistic children with ophthalmic and systemic
      manifestations of vitamin A deficiency due to food faddism. Although vitamin A
      deficiency is common in the developing world, reports in developed societies are
      rare. Our patients presented over a 1-year period. The patients were 14 and 13
      years old at the time of presentation and were both found to have marked features
      of vitamin A deficiency related to unusual dietary habits. Anterior segment signs
      of xerophthalmia were present in both patients. In addition, patient 1 showed
      evidence of a rod-predominant retinopathy, which resolved with vitamin A
      supplementation. Due to its rare occurrence, hypovitaminosis A must be
      highlighted and anticipated in this cohort. 

PMID- 25759667
TI  - A rod-sparing retinopathy in bardet-biedl syndrome.
AB  - Bardet-Biedl syndrome is a continuum of disorders characterized by systemic and
      ocular findings. Retinal abnormalities typically present as diffuse photoreceptor
      degeneration. Here, we report a novel case that suggests a rod-sparing variant of
      Bardet-Biedl syndrome. 

PMID- 25759668
TI  - A case of childhood vitrectomy performed for dense vitreous hemorrhage secondary
      to leukemia therapy and tumor lysis syndrome.
AB  - PURPOSE: To report a case of vitrectomy performed in a child with dense massive
      vitreous hemorrhage due to secondary acute myelogenous leukemia (AML) and tumor
      lysis syndrome. CASE: A 4-year-old boy with clear-cell renal cell carcinoma was
      successfully treated with chemotherapy in 2011. However, in May 2012, he
      developed secondary AML. Although he was treated with combined chemotherapy and
      radiation, tumor lysis syndrome occurred with renal and heart failure
      complications. After an ultrasound examination by pediatricians found bilateral
      subretinal protrusions, he was referred to our clinic. Fundus examinations
      confirmed that the protrusions were bilateral subretinal or choroidal
      hemorrhages. A few weeks later, dense vitreous hemorrhages occurred bilaterally,
      and he completely lost vision in both eyes. Electroretinograms were extinguished
      in both eyes. After improvement of his general condition, we performed a 25-gauge
      vitrectomy combined with lens extraction in his left eye in December 2012. After
      removal of the vitreous hemorrhage, we found the subretinal hemorrhage had
      already been absorbed, leaving a mottled fundus color. However, the optic disc
      was not pale. Nine months after the surgery, his best-corrected visual acuity
      finally improved to 0.1. CONCLUSION: We successfully treated a case of severe
      vitreous hemorrhage secondary to leukemia therapy and tumor lysis syndrome using
      25-gauge vitrectomy. This procedure may be safe and effective to perform, even in
      children with complications.

PMID- 25759669
TI  - The importance of iron in pathophysiologic conditions.

PMID- 25759670
TI  - The Open Physiology workflow: modeling processes over physiology circuitboards of
      interoperable tissue units.
AB  - A key challenge for the physiology modeling community is to enable the searching,
      objective comparison and, ultimately, re-use of models and associated data that
      are interoperable in terms of their physiological meaning. In this work, we
      outline the development of a workflow to modularize the simulation of tissue
      level processes in physiology. In particular, we show how, via this approach, we
      can systematically extract, parcellate and annotate tissue histology data to
      represent component units of tissue function. These functional units are
      semantically interoperable, in terms of their physiological meaning. In
      particular, they are interoperable with respect to [i] each other and with
      respect to [ii] a circuitboard representation of long-range advective routes of
      fluid flow over which to model long-range molecular exchange between these units.
      We exemplify this approach through the combination of models for physiology-based
      pharmacokinetics and pharmacodynamics to quantitatively depict biological
      mechanisms across multiple scales. Links to the data, models and software
      components that constitute this workflow are found at http://open
      physiology.org/. 

PMID- 25759671
TI  - Changes in mitochondrial function and mitochondria associated protein expression
      in response to 2-weeks of high intensity interval training.
AB  - PURPOSE: High-intensity short-duration interval training (HIT) stimulates
      functional and metabolic adaptation in skeletal muscle, but the influence of HIT
      on mitochondrial function remains poorly studied in humans. Mitochondrial
      metabolism as well as mitochondrial-associated protein expression were tested in
      untrained participants performing HIT over a 2-week period. METHODS: Eight males
      performed a single-leg cycling protocol (12 * 1 min intervals at 120% peak power
      output, 90 s recovery, 4 days/week). Muscle biopsies (vastus lateralis) were
      taken pre- and post-HIT. Mitochondrial respiration in permeabilized fibers,
      citrate synthase (CS) activity and protein expression of peroxisome proliferator
      activated receptor gamma coactivator (PGC-1alpha) and respiratory complex
      components were measured. RESULTS: HIT training improved peak power and time to
      fatigue. Increases in absolute oxidative phosphorylation (OXPHOS) capacities and
      CS activity were observed, but not in the ratio of CCO to the electron transport
      system (CCO/ETS), the respiratory control ratios (RCR-1 and RCR-2) or
      mitochondrial-associated protein expression. Specific increases in OXPHOS flux
      were not apparent after normalization to CS, indicating that gross changes mainly
      resulted from increased mitochondrial mass. CONCLUSION: Over only 2 weeks HIT
      significantly increased mitochondrial function in skeletal muscle independently
      of detectable changes in mitochondrial-associated and mitogenic protein
      expression.

PMID- 25759672
TI  - A computational investigation of feedforward and feedback processing in
      metacontrast backward masking.
AB  - In human perception studies, visual backward masking has been used to understand
      the temporal dynamics of subliminal vs. conscious perception. When a brief target
      stimulus is followed by a masking stimulus after a short interval of <100 ms,
      performance on the target is impaired when the target and mask are in close
      spatial proximity. While the psychophysical properties of backward masking have
      been studied extensively, there is still debate on the underlying cortical
      dynamics. One prevailing theory suggests that the impairment of target
      performance due to the mask is the result of lateral inhibition between the
      target and mask in feedforward processing. Another prevailing theory suggests
      that this impairment is due to the interruption of feedback processing of the
      target by the mask. This computational study demonstrates that both aspects of
      these theories may be correct. Using a biophysical model of V1 and V2, visual
      processing was modeled as interacting neocortical attractors, which must
      propagate up the visual stream. If an activating target attractor in V1 is
      quiesced enough with lateral inhibition from a mask, or not reinforced by
      recurrent feedback, it is more likely to burn out before becoming fully active
      and progressing through V2 and beyond. Results are presented which simulate
      metacontrast backward masking with an increasing stimulus interval and with the
      presence and absence of feedback activity. This showed that recurrent feedback
      diminishes backward masking effects and can make conscious perception more
      likely. One model configuration presented a metacontrast noise mask in the same
      hypercolumns as the target, and produced type-A masking. A second model
      configuration presented a target line with two parallel adjacent masking lines,
      and produced type-B masking. Future work should examine how the model extends to
      more complex spatial mask configurations. 

PMID- 25759673
TI  - Individual differences in vagal regulation are related to testosterone responses
      to observed violence.
AB  - Observing violent content has been hypothesized to facilitate antisocial
      behaviors including interpersonal violence. Testosterone is released in response
      to perceived challenges of social status, often followed by an increase in
      aggressive behaviors and physiological activation. Prior investigations
      evaluating the impact of observing violence on autonomic function have focused on
      sympathetic measures of arousal. Measurement of parasympathetic nervous system
      (PNS) activity has been neglected, although reduced PNS activity has been
      associated with antisocial behavior. Consistent with a hierarchical model of the
      autonomic nervous system (i.e., polyvagal theory), individual differences in PNS
      activity reflected in respiratory sinus arrhythmia (RSA) were hypothesized to
      have an inhibitory impact on sympathetic and hormonal reactivity in subjects who
      were observing a violent video. Autonomic data (i.e., electrodermal activity
      (EDA), heart rate, and RSA) were collected from forty adult males prior to and
      while viewing violent sports or a control video. Pre- and post-video saliva
      samples were assayed for cortisol and testosterone. Participants who viewed the
      violent video showed increased sympathetic activity compared to controls. In
      contrast to the sympathetic reactivity to the violent video, there were no
      significant RSA changes in response to the stimuli, suggesting that viewing
      violent sports selectively increases sympathetic activity without eliciting PNS
      withdrawal. However, within the group viewing the violent video, participants
      with lower RSA during baseline and the observation of violent videos, responded
      with greater increases in salivary testosterone, suggesting that high
      parasympathetic tone dampens testosterone reactivity. These individual
      differences in response to observed violence, associated with higher RSA, may
      account for some of the improved health, growth, and restoration outcomes across
      the lifespan, that this segment of the population benefits from. 

PMID- 25759674
TI  - Supramodal executive control of attention.
AB  - The human attentional system can be subdivided into three functional networks of
      alerting, orienting, and executive control. Although these networks have been
      extensively studied in the visuospatial modality, whether the same mechanisms are
      deployed across different sensory modalities remains unclear. In this study we
      used the attention network test for the visuospatial modality, in addition to two
      auditory variants with spatial and frequency manipulations to examine cross-modal
      correlations between network functions. Results showed that among the visual and
      auditory tasks, the effects of executive control, but not effects of alerting and
      orienting, were significantly correlated. These findings suggest that while
      alerting and orienting functions rely more upon modality-specific processes, the
      executive control of attention coordinates complex behavior via supramodal
      mechanisms. 

PMID- 25759675
TI  - Dissociative symptomatology in cancer patients.
AB  - INTRODUCTION: The utilization of the post-traumatic stress disorder (PTSD)
      diagnostic spectrum is currently being debated to categorize psychological
      adjustment in cancer patients. The aims of this study were to: (1) evaluate the
      presence of cancer-related traumatic dissociative symptomatology in a sample of
      cancer patients; (2) examine the correlation of cancer-related dissociation and
      sociodemographic and medical variables, anxiety, depression, and post-traumatic
      stress symptomatology; (3) investigate the predictors of cancer-related
      dissociation. METHODS: Ninety-two mixed cancer patients (mean age: 58.94, ds =
      10.13) recruited from two hospitals in northern Italy were administered a
      questionnaire on sociodemographic and medical characteristics, the Karnofsky
      Scale to measure the level of patient activity and medical care requirements, the
      Hospital Anxiety and Depression Scale (HADS) to evaluate the presence of anxiety
      and depression, the Impact of Event Scale Revised (IES-R) to assess the severity
      of intrusion, avoidance, and hypervigilance, and the Peritraumatic Dissociative
      Experiences Questionnaire (PDEQ) to quantify the traumatic dissociative
      symptomatology. RESULTS: 31.5% of participants report a PDEQ score above the
      cutoff. The results indicated that dissociative symptomatology was positively
      correlated with HADS scores (HADS-Anxiety: r = 0.476, p < 0.001; HADS-Depression:
      r = 0.364, p < 0.001) and with IES-R scores (IES-R-Intrusion: r = 0.698, p <
      0.001; IES-R-Avoidance: r = 0.619, p < 0.001; IES-R- Hypervigilance: r = 0.681, p
      < 0.001). A stepwise regression analysis was performed in order to find the
      predictors of cancer-related traumatic dissociative symptomatology. The results
      converged on a three predictor model revealing that IES-R-Intrusion, IES-R
      Avoidance, and IES-R-Hyperarousal accounted for 53.9% of the explained variance.
      CONCLUSION: These findings allow us to hypothesize a specific psychological
      reaction which may be ascribed to the traumatic spectrum within the context of
      cancer, emphasizing the close relationship between the origin of dissociative
      constituents which, according to the scientific literature, compose the traumatic
      experience. Our results have implications for understanding dissociative
      symptomatology in a cancer population and can help develop clinical programs of
      prevention and support for patients.

PMID- 25759676
TI  - Integrating emotion regulation and emotional intelligence traditions: a meta
      analysis.
AB  - Two relatively independent research traditions have developed that address
      emotion management. The first is the emotion regulation (ER) tradition, which
      focuses on the processes which permit individuals to influence which emotions
      they have, when they have them, and how they experience and express these
      emotions. The second is the emotional intelligence (EI) tradition, which focuses
      among other things-on individual differences in ER. To integrate these two
      traditions, we employed the process model of ER (Gross, 1998b) to review the
      literature on EI. Two key findings emerged. First, high EI individuals shape
      their emotions from the earliest possible point in the emotion trajectory and
      have many strategies at their disposal. Second, high EI individuals regulate
      their emotions successfully when necessary but they do so flexibly, thereby
      leaving room for emotions to emerge. We argue that ER and EI traditions stand to
      benefit substantially from greater integration. 

PMID- 25759677
TI  - Exploring manual asymmetries during grasping: a dynamic causal modeling approach.
AB  - Recording of neural activity during grasping actions in macaques showed that
      grasp-related sensorimotor transformations are accomplished in a circuit
      constituted by the anterior part of the intraparietal sulcus (AIP), the ventral
      (F5) and the dorsal (F2) region of the premotor area. In humans, neuroimaging
      studies have revealed the existence of a similar circuit, involving the putative
      homolog of macaque areas AIP, F5, and F2. These studies have mainly considered
      grasping movements performed with the right dominant hand and only a few studies
      have measured brain activity associated with a movement performed with the left
      non-dominant hand. As a consequence of this gap, how the brain controls for
      grasping movement performed with the dominant and the non-dominant hand still
      represents an open question. A functional magnetic resonance imaging (fMRI)
      experiment has been conducted, and effective connectivity (dynamic causal
      modeling, DCM) was used to assess how connectivity among grasping-related areas
      is modulated by hand (i.e., left and right) during the execution of grasping
      movements toward a small object requiring precision grasping. Results underlined
      boosted inter-hemispheric couplings between dorsal premotor cortices during the
      execution of movements performed with the left rather than the right dominant
      hand. More specifically, they suggest that the dorsal premotor cortices may play
      a fundamental role in monitoring the configuration of fingers when grasping
      movements are performed by either the right and the left hand. This role becomes
      particularly evident when the hand less-skilled (i.e., the left hand) to perform
      such action is utilized. The results are discussed in light of recent theories
      put forward to explain how parieto-frontal connectivity is modulated by the
      execution of prehensile movements. 

PMID- 25759678
TI  - Virtual action and real action have different impacts on comprehension of
      concrete verbs.
AB  - In the last decade, many results have been reported supporting the hypothesis
      that language has an embodied nature. According to this theory, the sensorimotor
      system is involved in linguistic processes such as semantic comprehension. One of
      the cognitive processes emerging from the interplay between action and language
      is motor simulation. The aim of the present study is to deepen the knowledge
      about the simulation of action verbs during comprehension in a virtual reality
      setting. We compared two experimental conditions with different motor tasks: one
      in which the participants ran in a virtual world by moving the joypad knob with
      their left hand (virtual action performed with their feet plus real action
      performed with the hand) and one in which they only watched a video of runners
      and executed an attentional task by moving the joypad knob with their left hand
      (no virtual action plus real action performed with the hand). In both conditions,
      participants had to perform a concomitant go/no-go semantic task, in which they
      were asked to press a button (with their right hand) when presented with a
      sentence containing a concrete verb, and to refrain from providing a response
      when the verb was abstract. Action verbs described actions performed with hand,
      foot, or mouth. We recorded electromyography (EMG) latencies to measure reaction
      times of the linguistic task. We wanted to test if the simulation occurs, whether
      it is triggered by the virtual or the real action, and which effect it produces
      (facilitation or interference). Results underlined that those who virtually ran
      in the environment were faster in understanding foot-action verbs; no simulation
      effect was found for the real action. The present findings are discussed in the
      light of the embodied language framework, and a hypothesis is provided that
      integrates our results with those in literature. 

PMID- 25759679
TI  - Review of neural rehabilitation programs for dyslexia: how can an allophonic
      system be changed into a phonemic one?
AB  - Neural investigations suggest that there are three possible core deficits in
      dyslexia: phonemic, grapho-phonemic, and graphemic. These investigations also
      suggest that the phonemic deficit resides in a different mode of speech
      perception which is based on allophonic (subphonemic) units rather than phonemic
      units. Here we review the results of remediation methods that tap into each of
      these core deficits, and examine how the methods that tap into the phonemic
      deficit might contribute to the remediation of allophonic perception. Remediation
      of grapho-phonemic deficiencies with a new computerized phonics training program
      (GraphoGame) might be able to surpass the limits of classical phonics training
      programs, particularly with regard to reading fluency. Remediation of visuo
      graphemic deficiencies through exposure to enhanced letter spacing is also
      promising, although children with dyslexia continued to read more slowly than
      typical readers after this type of training. Remediation of phonemic deficiencies
      in dyslexia with programs based solely on phonemic awareness has a limited impact
      on reading. This might be due to the persistence of a covert deficit in phonemic
      perception. Methods based on slowed speech enhance the perception not only of
      phonemic features but also of allophonic features, and this is probably why they
      have not been found to be effective in meta-analyses. Training of phonemic
      perception with a perceptual fading paradigm, a method that improves precision in
      identification and discrimination around phonemic boundaries, has yielded
      promising results. However, studies with children at risk for dyslexia and
      dyslexic adults have found that even when behavioral data do not reflect
      allophonic perception, it can nevertheless be present in neural recordings.
      Further investigations should seek to confirm that the perceptual fading paradigm
      is beneficial for reading, and that it renders perception truly phonemic. 

PMID- 25759680
TI  - A new account of the conditioning bias to out-groups.

PMID- 25759681
TI  - Progressive cognitive impairment evolving to dementia parallels parieto-occipital
      and temporal enlargement in idiopathic chronic hydrocephalus: a retrospective
      cohort study.
AB  - Little is known regarding progressive enlargement of the ventricular system in
      symptomatic patients or asymptomatic subjects. Before eventual surgical
      treatment, we evaluated the clinical and radiological features of an extremely
      rare group of patients with idiopathic chronic hydrocephalus (ICH) and cognitive
      impairment evolving to dementia (n = 11), and an extremely rare group of
      asymptomatic or minimally symptomatic adults (AMSA) with ventricular enlargement
      (n = 10). We quantified changes over time in the ventricular frontal, occipital,
      and temporal horns by measuring the Evans' index plus a parieto-occipital ratio
      and a temporal ratio, and their percentage of progression. Cerebral ventricles
      expanded over very long term in both demented patients with ICH and in AMSA. In
      AMSA, frontal enlargement predominated, whereas demented patients showed
      predominant parieto-occipital (p = 0.00) and temporal (p = 0.00) enlargement that
      progressed faster than in AMSA (p = 0.00). In ICH, progression of cognitive
      impairment parallels ventricular parieto-occipital and temporal horn enlargement.
      Limitations of this study are the retrospective nature, the non-uniform use of
      neuropsychological tests, the reduced sample size due to the extremely stringent
      enrollment criteria, the inability to determine the precise rate of progression. 

PMID- 25759682
TI  - Will crystal parkin help in understanding the future of Parkinson's disease?

PMID- 25759683
TI  - The small molecule fenpropimorph rapidly converts chloroplast membrane lipids to
      triacylglycerols in Chlamydomonas reinhardtii.
AB  - Concern about global warming has prompted an intense interest in developing
      economical methods of producing biofuels. Microalgae provide a promising platform
      for biofuel production, because they accumulate high levels of lipids, and do not
      compete with food or feed sources. However, current methods of producing algal
      oil involve subjecting the microalgae to stress conditions, such as nitrogen
      deprivation, and are prohibitively expensive. Here, we report that the fungicide
      fenpropimorph rapidly causes high levels of neutral lipids to accumulate in
      Chlamydomonas reinhardtii cells. When treated with fenpropimorph (10 MUg mL(-1))
      for 1 h, Chlamydomonas cells accumulated at least fourfold the amount of
      triacylglycerols (TAGs) present in the untreated control cells. Furthermore, the
      quantity of TAGs present after 1 h of fenpropimorph treatment was over twofold
      higher than that formed after 9 days of nitrogen starvation in medium with no
      acetate supplement. Biochemical analysis of lipids revealed that the accumulated
      TAGs were derived mainly from chloroplast polar membrane lipids. Such a
      conversion of chloroplast polar lipids to TAGs is desirable for biodiesel
      production, because polar lipids are usually removed during the biodiesel
      production process. Thus, our data exemplified that a cost and time effective
      method of producing TAGs is possible using fenpropimorph or similar drugs. 

PMID- 25759684
TI  - Computational approaches for prediction of pathogen-host protein-protein
      interactions.
AB  - Infectious diseases are still among the major and prevalent health problems,
      mostly because of the drug resistance of novel variants of pathogens. Molecular
      interactions between pathogens and their hosts are the key parts of the infection
      mechanisms. Novel antimicrobial therapeutics to fight drug resistance is only
      possible in case of a thorough understanding of pathogen-host interaction (PHI)
      systems. Existing databases, which contain experimentally verified PHI data,
      suffer from scarcity of reported interactions due to the technically challenging
      and time consuming process of experiments. These have motivated many researchers
      to address the problem by proposing computational approaches for analysis and
      prediction of PHIs. The computational methods primarily utilize sequence
      information, protein structure and known interactions. Classic machine learning
      techniques are used when there are sufficient known interactions to be used as
      training data. On the opposite case, transfer and multitask learning methods are
      preferred. Here, we present an overview of these computational approaches for
      predicting PHI systems, discussing their weakness and abilities, with future
      directions. 

PMID- 25759686
TI  - Resource niche overlap promotes stability of bacterial community metabolism in
      experimental microcosms.
AB  - Decomposition of organic matter is an important ecosystem process governed in
      part by bacteria. The process of decomposition is expected to benefit from
      interspecific bacterial interactions such as resource partitioning and
      facilitation. However, the relative importance of resource niche breadth
      (metabolic diversity) and resource niche overlap (functional redundancy) on
      decomposition and the temporal stability of ecosystem processes received little
      scientific attention. Therefore, this study aims to evaluate the effect of an
      increase in bacterial community resemblance on both decomposition and the
      stability of bacterial metabolism in aquatic sediments. To this end, we performed
      laboratory microcosm experiments in which we examined the influence of bacterial
      consortia differing in number and composition of species on bacterial activity
      (Electron Transport System Activity, ETSA), dissolved organic carbon production
      and wavelet transformed measurements of redox potential (Eh). Single substrate
      affinities of the individual bacterial species were determined in order to
      calculate the metabolic diversity of the microbial community. Results presented
      here indicate that bacterial activity and organic matter decomposition increase
      with widening of the resource niche breadth, and that metabolic stability
      increases with increasing overlap in bacterial resource niches, hinting that
      resource niche overlap can promote the stability of bacterial community
      metabolism. 

PMID- 25759685
TI  - Mechanism of coupling drug transport reactions located in two different
      membranes.
AB  - Gram- negative bacteria utilize a diverse array of multidrug transporters to pump
      toxic compounds out of the cell. Some transporters, together with periplasmic
      membrane fusion proteins (MFPs) and outer membrane channels, assemble trans
      envelope complexes that expel multiple antibiotics across outer membranes of Gram
      negative bacteria and into the external medium. Others further potentiate this
      efflux by pumping drugs across the inner membrane into the periplasm. Together
      these transporters create a powerful network of efflux that protects bacteria
      against a broad range of antimicrobial agents. This review is focused on the
      mechanism of coupling transport reactions located in two different membranes of
      Gram-negative bacteria. Using a combination of biochemical, genetic and
      biophysical approaches we have reconstructed the sequence of events leading to
      the assembly of trans-envelope drug efflux complexes and characterized the roles
      of periplasmic and outer membrane proteins in this process. Our recent data
      suggest a critical step in the activation of intermembrane efflux pumps, which is
      controlled by MFPs. We propose that the reaction cycles of transporters are
      tightly coupled to the assembly of the trans-envelope complexes. Transporters and
      MFPs exist in the inner membrane as dormant complexes. The activation of
      complexes is triggered by MFP binding to the outer membrane channel, which leads
      to a conformational change in the membrane proximal domain of MFP needed for
      stimulation of transporters. The activated MFP-transporter complex engages the
      outer membrane channel to expel substrates across the outer membrane. The
      recruitment of the channel is likely triggered by binding of effectors
      (substrates) to MFP or MFP-transporter complexes. This model together with recent
      structural and functional advances in the field of drug efflux provides a fairly
      detailed understanding of the mechanism of drug efflux across the two membranes. 

PMID- 25759687
TI  - Induction and differential expression of certain novel proteins in Anabaena L31
      under UV-B radiation stress.
AB  - For examining how UV-B radiation alters the proteome of the N2-fixing
      cyanobacterium, Anabaena L31, we extracted proteins from cultures irradiated with
      UV-B + white light and controls (white light irradiated) and analyzed the
      proteins using two-dimensional gel electrophoresis and matrix-assisted laser
      desorption/ionization time of flight mass spectrometry (MALDI-TOF MS). Twenty one
      proteins, including two hypothetical proteins (HPs) were identified and placed in
      eight functional categories. However several of the proteins were housekeeping
      proteins involved in key metabolic processes such as carbon, amino acid
      biosynthesis and energy metabolism, certain proteins seem to have a role in
      stress (antioxidative enzymes), translation, cellular processes and reductases.
      Two novel HPs (all3797 and all4050) were characterized in detail. These two were
      over-expressed after UV-B irradiation and characterized as FAS 1 (all3797) and
      PRC barrel-like (all4050) proteins. Bioinformatics analysis revealed that the
      genes of both the HPs have promoter regions as well as transcription binding
      sites in their upstream region (UTR). Promoters present in all3797 genes suggest
      their crucial role against UV-B and certain other abiotic stresses. To our
      knowledge these novel proteins have not been previously reported in any Anabaena
      strains subjected to UV-B stress. Although we have focused our study on a limited
      number of proteins, results obtained shed light on the highly complicated but
      poorly studied aspect of UV-B radiation-mediated changes in the proteome and
      expression of proteins in cyanobacteria. 

PMID- 25759688
TI  - A comprehensive analysis of the microbial communities of healthy and diseased
      marine macroalgae and the detection of known and potential bacterial pathogens.
AB  - Microorganisms are increasingly being recognized as the causative agents in the
      diseases of marine higher organisms, such as corals, sponges, and macroalgae.
      Delisea pulchra is a common, temperate red macroalga, which suffers from a
      bleaching disease. Two bacterial strains, Nautella italica R11 and Phaeobacter
      gallaeciensis LSS9, have been shown in vitro to cause bleaching symptoms, but
      previous work has failed to detect them during a natural bleaching event. To
      provide a link between in vitro observations and natural occurrences of the
      disease, we employ here deep-sequencing of the 16S rRNA gene to comprehensively
      analyze the community composition of healthy and diseased D. pulchra samples from
      two separate locations. We observed operational taxonomic units (OTUs) with 100%
      identity and coverage to the 16S RNA gene sequence of both in vitro pathogens,
      but only the OTU with similarity to strain LSS9 showed a statistically
      significant higher abundance in diseased samples. Our analysis also reveals the
      existence of other bacterial groups within the families Rhodobacteraceae and
      Flavobacteriaceae that strongly contribute to difference between diseased and
      healthy samples and thus these groups potentially contain novel macroalgal
      pathogens and/or saprophytes. Together our results provide evidence for the
      ecological relevance of one kind of in vitro pathogen, but also highlight the
      possibility that multiple opportunistic pathogens are involved in the bleaching
      disease of D. pulchra. 

PMID- 25759689
TI  - Drug-resistant tuberculosis can be predicted by Mycobacterial interspersed
      repetitive unit locus.
AB  - It is unknown whether MIRU-VNTR (Mycobacterial Interspersed Repetitive Unit
      Variable Number of Tandem Repeat) is associated with drug resistance of
      Mycobacterium tuberculosis. The purpose of this study was to explore the ability
      of 24 MIRU loci to predict the drug resistance of Isoniazid (INH), Rifampicin
      (RFP), Streptomycin (SM), Ethambutol (EMB) and Pyrazinamide (PZA). We collected
      the drug resistance and MIRU loci information of 109 strains of M. tuberculosis
      from an open database. The results of multivariate logistic regression showed
      that the VNTR polymorphism of MTUB04 was related to INH resistance [odds ratio
      (OR) = 2.82, P = 0.00], RFP resistance (OR = 1.91, P = 0.02), SM resistance (OR =
      1.98, P = 0.01) and EMB resistance (OR = 1.95, P = 0.03). MIRU40 was associated
      with INH resistance (OR = 2.22, P = 0.00). MTUB21 was connected with INH
      resistance (OR = 1.63, P = 0.02) and SM resistance (OR = 1.69, P = 0.01). MIRU26
      was correlated with SM resistance (OR = 1.52, P = 0.04). MIRU39 was associated
      with EMB resistance (OR = 4.07, P = 0.02). The prediction power of MIRU loci were
      0.84, 0.70, 0.85, and 0.74 respectively for INH (predicted by MTUB04, MIRU20, and
      MTUB21), RFP (predicted by MTUB04), SM (predicted by MTUB21 and MIRU26) and EMB
      (MTUB04 and MIRU39) through ROC analysis. Our results showed that MIRU loci were
      related to anti-tuberculosis drug and could predict the drug resistance of
      tuberculosis. 

PMID- 25759690
TI  - The new deal: a potential role for secreted vesicles in innate immunity and tumor
      progression.
AB  - Tumors must evade the immune system to survive and metastasize, although the
      mechanisms that lead to tumor immunoediting and their evasion of immune
      surveillance are far from clear. The first line of defense against metastatic
      invasion is the innate immune system that provides immediate defense through
      humoral immunity and cell-mediated components, mast cells, neutrophils,
      macrophages, and other myeloid-derived cells that protect the organism against
      foreign invaders. Therefore, tumors must employ different strategies to evade
      such immune responses or to modulate their environment, and they must do so prior
      metastasizing. Exosomes and other secreted vesicles can be used for cell-cell
      communication during tumor progression by promoting the horizontal transfer of
      information. In this review, we will analyze the role of such extracellular
      vesicles during tumor progression, summarizing the role of secreted vesicles in
      the crosstalk between the tumor and the innate immune system. 

PMID- 25759692
TI  - Dickkopf-3, a tissue-derived modulator of local T-cell responses.
AB  - The adaptive immune system protects organisms from harmful environmental insults.
      In parallel, regulatory mechanisms control immune responses in order to assure
      preservation of organ integrity. Yet, molecules involved in the control of T-cell
      responses in peripheral tissues are poorly characterized. Here, we investigated
      the function of Dickkopf-3 in the modulation of local T-cell reactivity. Dkk3 is
      a secreted, mainly tissue-derived protein with highest expression in organs
      considered as immune-privileged such as the eye, embryo, placenta, and brain.
      While T-cell development and activation status in naive Dkk3-deficient mice was
      comparable to littermate controls, we found that Dkk3 contributes to the
      immunosuppressive microenvironment that protects transplanted, class-I mismatched
      embryoid bodies from T-cell-mediated rejection. Moreover, genetic deletion or
      antibody-mediated neutralization of Dkk3 led to an exacerbated experimental
      autoimmune encephalomyelitis (EAE). This phenotype was accompanied by a change of
      T-cell polarization displayed by an increase of IFNgamma-producing T cells within
      the central nervous system. In the wild-type situation, Dkk3 expression in the
      brain was up-regulated during the course of EAE in an IFNgamma-dependent manner.
      In turn, Dkk3 decreased IFNgamma activity and served as part of a negative
      feedback mechanism. Thus, our findings suggest that Dkk3 functions as a tissue
      derived modulator of local CD4(+) and CD8(+) T-cell responses. 

PMID- 25759691
TI  - Childhood obesity: immune response and nutritional approaches.
AB  - Childhood obesity is characterized by a low-grade inflammation status depending
      on the multicellular release of cytokines, adipokines, and reactive oxygen
      species. In particular, the imbalance between anti-inflammatory T regulatory
      cells and inflammatory T helper 17 cells seems to sustain such a phlogistic
      condition. Alterations of gut microbiota since childhood also contribute to the
      maintenance of inflammation. Therefore, besides preventive measures and caloric
      restrictions, dietary intake of natural products endowed with anti-oxidant and
      anti-inflammatory activities may represent a valid interventional approach for
      preventing and/or attenuating the pathological consequences of obesity. In this
      regard, the use of prebiotics, probiotics, polyphenols, polyunsaturated fatty
      acids, vitamins, and melatonin in human clinical trials will be described. 

PMID- 25759694
TI  - Eotaxin-1 (CCL11).

PMID- 25759693
TI  - Control of cytokine production by human fc gamma receptors: implications for
      pathogen defense and autoimmunity.
AB  - Control of cytokine production by immune cells is pivotal for counteracting
      infections via orchestration of local and systemic inflammation. Although their
      contribution has long been underexposed, it has recently become clear that human
      Fc gamma receptors (FcgammaRs), which are receptors for the Fc region of
      immunoglobulin G (IgG) antibodies, play a critical role in this process by
      controlling tissue- and pathogen-specific cytokine production. Whereas individual
      stimulation of FcgammaRs does not evoke cytokine production, FcgammaRs cell-type
      specifically interact with various other receptors for selective amplification or
      inhibition of particular cytokines, thereby tailoring cytokine responses to the
      immunological context. The physiological function of FcgammaR-mediated control of
      cytokine production is to counteract infections with various classes of
      pathogens. Upon IgG opsonization, pathogens are simultaneously recognized by
      FcgammaRs as well as by various pathogen-sensing receptors, leading to the
      induction of pathogen class-specific immune responses. However, when erroneously
      activated, the same mechanism also contributes to the development of autoimmune
      diseases such as rheumatoid arthritis and systemic lupus erythematosus. In this
      review, we discuss control of cytokine production as a novel function of
      FcgammaRs in human innate immune cells in the context of homeostasis, infection,
      and autoimmunity and address the possibilities for future therapeutic
      exploitation. 

PMID- 25759695
TI  - beta2-Microglobulin and TIMP1 Are Linked Together in Cardiorenal Remodeling and
      Failure.
AB  - BACKGROUND/AIMS: The cardiorenal syndrome is a complication in patients
      hospitalized with chronic heart failure (CHF). The beta2-microglobulin (b2M)
      level is an index of decreased glomerular filtration rate (GFR), tissue turnover
      and inflammation. It is an emerging new predictive marker of cardiovascular
      events and mortality, but its role as a biomarker of cardiorenal remodeling and
      failure is still unknown. TIMP1, an endogenous tissue inhibitor of activated
      matrix metalloproteinases, is a biomarker of heart remodeling and failure. We
      aimed to evaluate the circulating profile of b2M and TIMP1 in CHF patients, in
      sedentary controls with no tissue remodeling and in veteran athletes with
      physiological cardiorenal remodeling and athlete's heart (AH). METHODS: We
      investigated the plasma levels of b2M and TIMP1 in 24 subjects with CHF without
      primitive renal disease, in 25 sedentary controls and in 30 veteran marathoners
      with AH over 50 years. RESULTS: The b2M and TIMP1 levels were higher in CHF
      patients, and there was a correlation between them (r = 0.5287, p < 0.0095). The
      b2M level correlated with the severity of cardiorenal impairment: with proBNP (r
      = 0.66, p > 0.0007), percent ejection fraction (r = -0.56, p = 0.0162) and GFR (r
      = 0.83, p < 0.0001). b2M was also correlated with TIMP1 in AH subjects (r =
      0.7548, p < 0.0001) but not in controls. This correlation was independent from
      GFR in both CHF patients and sedentary controls. CONCLUSIONS: In CHF patients,
      the plasma levels of b2M and TIMP1 were linked together and correlated with the
      severity of cardiorenal failure. Moreover, a strong correlation between b2M and
      TIMP1 characterized cardiovascular remodeling not only in CHF patients but also
      in AH subjects. These findings suggest that clinicians should use b2M and TIMP1
      as associated biomarkers of cardiorenal remodeling and failure.

PMID- 25759696
TI  - Clinical prediction scores for type 1 cardiorenal syndrome derived and validated
      in chinese cohorts.
AB  - Type 1 cardiorenal syndrome is one of the major diseases threatening human life
      in China. The incidence of acute kidney injury (AKI) associated with acute heart
      failure (AHF), acute myocardial infarction (AMI), cardiac surgery, and coronary
      angiography has been reported to be 32.2, 14.7, 40.2, and 4.5%, respectively. In
      the past 2 years, we derived and validated 4 risk scores for the prediction of
      AKI associated with the above acute heart diseases as well as for examination and
      treatment in Chinese cohorts. A univariable comparison and a subsequent
      multivariate logistic regression analysis of the potential predictive variables
      of AKI in the derivation set were conducted and used to establish the prediction
      scores, which were then verified in the validation set. The area under the
      receiver operating characteristic (ROC) curve and the Hosmer-Lemeshow goodness-of
      fit statistic test were performed to assess the discrimination and calibration of
      the prediction scores, respectively. These 4 prediction scores all showed
      adequate discrimination (area under the ROC curve, >=0.70) and good calibration
      (p > 0.05). Both Forman's risk score (for AKI associated with AHF) and Mehran's
      risk score (for AKI associated with coronary angiography) are widely applied
      around the world. The external validation of these 2 risk scores was performed in
      our patients, but their discriminative power was quite low (area under the ROC
      curve, 0.65 and 0.57, respectively). Therefore, these prediction scores derived
      from Chinese cohorts might be more accurate than those derived from different
      races when they are applied in Chinese patients. 

PMID- 25759697
TI  - Cardiac, Inflammatory and Metabolic Parameters: Hemodialysis versus Peritoneal
      Dialysis.
AB  - INTRODUCTION: Mortality in dialysis patients is higher than in the general
      population, and cardiovascular disease represents the leading cause of death.
      Hypertension and volume overload are important risk factors for the development
      of left ventricular hypertrophy (LVH) in hemodialysis (HD) and peritoneal
      dialysis (PD) patients. Other factors are mainly represented by
      hyperparathyroidism, vascular calcification, arterial stiffness and inflammation.
      The aim of this study was to compare blood pressure (BP) and metabolic parameters
      with cardiovascular changes [cardiothoracic ratio (CTR), aortic arch
      calcification (AAC) and LV mass index (LVMI)] between PD and HD patients.
      MATERIALS AND METHODS: 45 patients (23 HD and 22 PD patients) were enrolled. BP
      measurements, echocardiography and chest X-ray were performed in each patient to
      determine the LVMI and to evaluate the CTR and AAC. Inflammatory indexes, intact
      parathyroid hormone (iPTH) and arterial blood gas analysis were also evaluated.
      RESULTS: LVMI was higher in PD than HD patients (139 y 19 vs. 104 y 22; p =
      0.04). In PD patients, a significant correlation between iPTH, C-reactive protein
      and the presence of LVH was observed (r = 0.70, p = 0.04; r = 0.70, p = 0.03,
      respectively). The CTR was increased in PD patients as compared to HD patients,
      while no significant differences in cardiac calcifications were determined.
      CONCLUSIONS: Our data indicate that HD patients present more effective BP control
      than PD patients. Adequate fluid and metabolic control are necessary to assess
      the adequacy of BP, which is strongly correlated with the increase in LVMI and
      with the increased CTR in dialysis patients. PD is a home therapy and allows a
      better quality of life, but PD patients may present a further increased
      cardiovascular risk if not adequately monitored.

PMID- 25759698
TI  - The importance of contrast volume/glomerular filtration rate ratio in contrast
      induced nephropathy patients after transcatheter aortic valve implantation.
AB  - BACKGROUND/AIM: Transcatheter aortic valve implantation (TAVI) is a method which
      is increasingly applied in severe aortic stenosis treatment. The development of
      contrast-induced nephropathy (CIN) after TAVI increases morbidity and mortality
      rates. Within the scope of this study, the importance of the contrast medium
      volume to glomerular filtration rate (CV/GFR) ratio in determining the
      development of CIN and the amount of CV that could be applied was evaluated.
      METHODS: Seventy-two patients (aged 78.6 +/- 11.6 years; 38 females) who
      underwent aortic valve replacement with the TAVI method between June 2013 and
      August 2014 were included in the study. CIN was defined as an absolute increase
      in serum creatinine of >0.5 mg/dl or a relative increase of >25% within 48-72 h
      after TAVI. CIN+ and CIN-patients were classified into two groups. The chi(2)
      test, t test, Mann-Whitney U test, ROC analysis, and univariate and multivariate
      regression analyses were applied for statistical analyses. RESULTS: CIN was
      detected in 16 patients (22%) in our study. Baseline creatinine, baseline GFR,
      the Mehran risk score, CV, and the CV/GFR ratio were determined as the predictive
      factors of CIN development. A CV/GFR ratio of 3.9 was specified to predict CIN
      development with 71% sensitivity and 80% specificity. CONCLUSION: After TAVI, CIN
      may develop due to various reasons. In patients to whom TAVI was applied, the
      CV/GFR ratio may be a guideline helping to prevent the development of renal
      pathologies. The amount of contrast medium that can be given to a patient can be
      calculated in terms of baseline GFR.

PMID- 25759699
TI  - One-year survival and renal function recovery of acute kidney injury patients
      with chronic heart failure.
AB  - OBJECTIVE: To describe and analyze the clinical characteristics of acute kidney
      injury (AKI) patients with preexisting chronic heart failure (CHF) and to
      identify the prognostic factors of the 1-year outcome. METHODS: A total of 120
      patients with preexisting CHF who developed AKI between January 2005 and December
      2010 were enrolled. CHF was diagnosed according to the European Society of
      Cardiology guidelines, and AKI was diagnosed using the RIFLE criteria. Clinical
      characteristics were recorded, and nonrecovery from kidney dysfunction as well as
      mortality were analyzed. RESULTS: The median age of the patients was 70 years,
      and 58.33% were male. 60% of the patients had an advanced AKI stage ('failure')
      and 90% were classified as NYHA class III/IV. The 1-year mortality rate was 35%.
      25.83% of the patients progressed to end-stage renal disease after 1 year.
      Hypertension, anemia, coronary atherosclerotic heart disease and chronic kidney
      disease were common comorbidities. Multiple organ dysfunction syndrome (MODS; OR,
      35.950; 95% CI, 4.972-259.952), arrhythmia (OR, 13.461; 95% CI, 2.379-76.161),
      anemia (OR, 6.176; 95% CI, 1.172-32.544) and RIFLE category (OR, 5.353; 95% CI,
      1.436-19.952) were identified as risk factors of 1-year mortality. For 1-year
      nonrecovery from kidney dysfunction, MODS (OR, 8.884; 95% CI, 2.535-31.135) and
      acute heart failure (OR, 3.281; 95% CI, 1.026-10.491) were independent risk
      factors. CONCLUSION: AKI patients with preexisting CHF were mainly elderly
      patients who had an advanced AKI stage and NYHA classification. Their 1-year
      mortality and nonrecovery from kidney dysfunction rates were high. Identifying
      risk factors may help to improve their outcome.

PMID- 25759700
TI  - Kidney dysfunction and left ventricular assist device support: a comprehensive
      perioperative review.
AB  - Left ventricular assist devices (LVADs) are used increasingly as a bridge to
      transplantation or as destination therapy in end-stage heart failure patients who
      do not respond to optimal medical therapy. Many of these patients have end-organ
      dysfunction, including advanced kidney dysfunction, before and after LVAD
      implantation. Kidney dysfunction is a marker of adverse outcomes, such as
      increased morbidity and mortality. This review discusses kidney dysfunction and
      associated management strategies during the dynamic perioperative time period of
      LVAD implantation. Furthermore, we suggest potential future research directions
      to better understand the complex relationship between renal pathophysiology and
      mechanical circulatory support. 

PMID- 25759701
TI  - Contrast Volume/Raw eGFR Ratio for Predicting Contrast-Induced Acute Kidney
      Injury in Patients Undergoing Percutaneous Coronary Intervention for Myocardial
      Infarction.
AB  - BACKGROUND: Considering that contrast medium is excreted through the whole kidney
      in a similar manner to drug excretion, the use of raw estimated glomerular
      filtration rate (eGFR) rather than body surface area (BSA)-normalized eGFR is
      thought to be more appropriate for evaluating the risk of contrast-induced acute
      kidney injury (CI-AKI). METHODS: This study included 2,189 myocardial infarction
      patients treated with percutaneous coronary intervention. Logistic regression
      analysis was performed to identify the independent risk factors. We used receiver
      operating characteristic (ROC) curves to compare the ratios of contrast volume
      (CV) to eGFR with and without BSA normalization in predicting CI-AKI. RESULTS:
      The area under the curve (AUC) of the ROC curve for the model including all the
      significant variables such as diabetes mellitus, left ventricular ejection
      fraction, preprocedural glucose, and the CV/raw modification of diet in renal
      disease (MDRD) eGFR ratio was 0.768 [95% confidence interval (CI), 0.720-0.816; p
      < 0.001]. When the CV/raw MDRD eGFR ratio was used as a single risk value, the
      AUC of the ROC curve was 0.650 (95% CI, 0.590-0.711; p < 0.001). When the CV/MDRD
      eGFR ratio with BSA normalization ratio was used, the AUC of the ROC curve
      further decreased to 0.635 (95% CI, 0.574-0.696; p < 0.001). The difference
      between the two AUCs was significant (p = 0.002). CONCLUSIONS: Raw eGFR is a
      better predictor for CI-AKI than BSA-normalized eGFR.

PMID- 25759702
TI  - Neuronal nitric oxide synthase-dependent amelioration of diastolic dysfunction in
      rats with chronic renocardiac syndrome.
AB  - We have recently described the chronic renocardiac syndrome (CRCS) in rats with
      renal failure, cardiac dysfunction and low nitric oxide (NO) availability by
      combining subtotal nephrectomy and transient low-dose NO synthase (NOS)
      inhibition. Cardiac gene expression of the neuronal isoform of NOS (nNOS) was
      induced. Hence, we studied the role of nNOS, in vivo cardiac function and beta
      adrenergic response in our CRCS model by micromanometer/conductance catheter.
      Left ventricular (LV) hemodynamics were studied during administration of
      dobutamine (dobu), the highly specific irreversible inhibitor of nNOS L-VNIO [L
      N5-(1-Imino-3-butenyl)-ornithine], or both at steady state and during preload
      reduction. Rats with CRCS showed LV systolic dysfunction at baseline, together
      with prolonged diastolic relaxation and rightward shift of the end-systolic
      pressure-volume relationships. After L-VNIO infusion, diastolic relaxation of
      CRCS rats further prolonged. The time constant of active relaxation (tau)
      increased by 25 +/- 6% from baseline (p < 0.05), and the maximal rate of pressure
      decrease was 36 +/- 7% slower (p < 0.001). These variables did not change in
      controls. In our CRCS model, nNOS did not seem to affect systolic dysfunction. In
      summary, in this model of CRCS, blockade of nNOS further worsens diastolic
      dysfunction and L-VNIO does not influence inherent contractility and the response
      to dobu stress. 

PMID- 25759703
TI  - Floral bud damage compensation by branching and biomass allocation in genotypes
      of Brassica napus with different architecture and branching potential.
AB  - Plant branching is a key process in the yield elaboration of winter oilseed rape
      (WOSR). It is also involved in plant tolerance to flower damage because it allows
      the setting of new fertile inflorescences. Here we characterize the changes in
      the branching and distribution of the number of pods between primary and
      secondary inflorescences in response to floral bud clippings. Then we investigate
      the impacts of the modifications in branching on the biomass allocation and its
      consequence on the crop productivity (harvest index). These issues were addressed
      on plants with contrasted architecture and branching potential, using three
      genotypes (Exocet, Pollen, and Gamin) grown under two levels of nitrogen
      fertilization. Clipping treatments of increasing intensities were applied to
      either inflorescences or flower buds. We were able to show that restoration of
      the number of pods after clipping is the main lever for the compensation.
      Genotypes presented different behaviors in branching and biomass allocation as a
      function of clipping treatments. The number of fertile ramifications increased
      for the high intensities of clipping. In particular, the growth of secondary
      ramifications carried by branches developed before clipping has been observed.
      The proportions of yield and of number of pods carried by these secondary axes
      increased and became almost equivalent to the proportion carried by primary
      inflorescences. In terms of biomass allocation, variations have also been
      evidenced in the relationship between pod dry mass on a given axis and the number
      of pods set, while the shoot/root ratio was not modified. The harvest index
      presented different responses: it decreased after flower buds clipping, while it
      was maintained after the clipping of the whole inflorescences. The results are
      discussed relative to their implications regarding the identification of
      interesting traits to be target in breeding programs in order to improve WOSR
      tolerance. 

PMID- 25759704
TI  - Genome-wide identification and expression analysis of auxin response factor gene
      family in Medicago truncatula.
AB  - Auxin response factors (ARFs) bind specifically to auxin response elements
      (AuxREs) in the promoters of down-stream target genes and play roles in plant
      responses to diverse environmental factors. Using the latest updated Medicago
      truncatula reference genome sequence, a comprehensive characterization and
      analysis of 24 MtARF (M. truncatula ARF) genes were performed. To uncover the
      basic information and functions of MtARF genes during symbiosis, we analyzed the
      expression patterns of MtARF genes during the early phase of Sinorhizobium
      meliloti infection. The systematic analysis indicated that changes in MtARF gene
      expression occur during these early stages of infection, suggesting a functional
      role in symbiosis. Furthermore, the roles of MtARF-mediated auxin signaling in
      symbiosis were tested in the infection resistant mutant (dmi3). The expression
      responses of MtARFs to S. meliloti infection were attenuated in the mutant
      compared to wild-type A17. In summary, our results show that changes in MtARF
      gene expression occur during the response to S. meliloti infection, suggesting
      that members of this family may have important roles in the symbiotic
      interaction. 

PMID- 25759705
TI  - Recent advances in the Zymoseptoria tritici-wheat interaction: insights from
      pathogenomics.
AB  - We examine the contribution of next generation sequencing (NGS) to our
      understanding of the interaction between the fungal pathogen Zymoseptoria tritici
      and its wheat host. Recent interspecific whole genome comparisons between Z.
      tritici and its close relatives provide evidence that Z. tritici has undergone
      strong adaptive evolution, which is attributed to specialization by Z. tritici on
      wheat. We also assess the contribution of recent RNA sequencing datasets toward
      identifying pathogen genes and mechanisms critical for disease. While these
      studies have yet to report a major effector gene, they illustrate that assembling
      reads to the reference genome is a robust method to identify fungal transcripts
      from in planta infections. They also highlight the strong influence that the
      wheat cultivar has on effector gene expression. Lastly, we suggest future
      directions for NGS-guided approaches to address largely unanswered questions
      related to cultivar and lifecycle dependent gene expression and propose that
      future experiments with Z. tritici be conducted on a single wheat cultivar to
      enable comparisons across experiments. 

PMID- 25759706
TI  - Induced resistance for plant defense.

PMID- 25759707
TI  - Patterns of late spring frost leaf damage and recovery in a European beech (Fagus
      sylvatica L.) stand in south-eastern Germany based on repeated digital
      photographs.
AB  - Damage by late spring frost is a risk deciduous trees have to cope with in order
      to optimize the length of their growing season. The timing of spring phenological
      development plays a crucial role, not only at the species level, but also at the
      population and individual level, since fresh new leaves are especially
      vulnerable. For the pronounced late spring frost in May 2011 in Germany, we
      studied the individual leaf development of 35 deciduous trees (mainly European
      beech Fagus sylvatica L.) at a mountainous forest site in the Bayerischer Wald
      National Park using repeated digital photographs. Analyses of the time series of
      greenness by a novel Bayesian multiple change point approach mostly revealed five
      change points which almost perfectly matched the expected break points in leaf
      development: (i) start of the first greening between day of the year (DOY) 108
      119 (mean 113), (ii) end of greening, and (iii) visible frost damage after the
      frost on the night of May 3rd/4th (DOY 123/124), (iv) re-sprouting 19-38 days
      after the frost, and (v) full maturity around DOY 178 (166-184) when all beech
      crowns had fully recovered. Since frost damage was nearly 100%, individual
      susceptibility did not depend on the timing of first spring leaf unfolding.
      However, we could identify significant patterns in fitness linked to an earlier
      start of leaf unfolding. Those individuals that had an earlier start of greening
      during the first flushing period had a shorter period of recovery and started the
      second greening earlier. Thus, phenological timing triggered the speed of
      recovery from such an extreme event. The maximum greenness achieved, however, did
      not vary with leaf unfolding dates. Two mountain ashes (Sorbus aucuparia L.) were
      not affected by the low temperatures of -5 degrees C. Time series analysis of
      webcam pictures can thus improve process-based knowledge and provide valuable
      insights into the link between phenological variation, late spring frost damage,
      and recovery within one stand. 

PMID- 25759708
TI  - Final Results of Cilostazol-Aspirin Therapy against Recurrent Stroke with
      Intracranial Artery Stenosis (CATHARSIS).
AB  - PURPOSE: To compare the effect of cilostazol plus aspirin versus aspirin alone on
      the progression of intracranial arterial stenosis (IAS), and to compare ischemic
      and hemorrhagic events in patients with symptomatic IAS, an investigator-driven,
      nationwide multicenter cooperative randomized controlled trial (CATHARSIS;
      ClinicalTrials.gov Identifier 00333164) was conducted. METHODS: 165
      noncardioembolic ischemic stroke patients with >50% stenosis in the responsible
      intracranial artery after 2 weeks to 6 months from the onset were randomly
      allocated to receive either cilostazol 200 mg/day plus aspirin 100 mg/day (n =
      83, CA group) or aspirin 100 mg/day alone (n = 82, A group). The primary endpoint
      was the progression of IAS on magnetic resonance angiography at 2 years after
      randomization. Secondary endpoints were any vascular events, any cause of death,
      serious adverse events, new silent brain infarcts, and worsening of the modified
      Rankin Scale score. RESULTS: Progression of IAS was observed in 9.6% of the CA
      group patients and in 5.6% of the A group patients, with no significant
      intergroup difference (p = 0.53). The incidence of the secondary endpoints tended
      to be lower in the CA group compared with the A group, although the differences
      were not significant. By using exploratory logistic regression analysis adjusted
      for patient background characteristics, it was shown that the risk for certain
      combinations of secondary endpoints was lower in the CA group than in the A group
      [all vascular events and silent brain infarcts: odds ratio (OR) = 0.37, p = 0.04;
      stroke and silent brain infarcts: OR = 0.34, p = 0.04; all vascular events,
      worsening of modified Rankin Scale scores and silent brain infracts: OR = 0.41, p
      = 0.03]. Major hemorrhage was observed in 4 patients of the CA group and in 3 of
      the A group. CONCLUSION: Progression of IAS during the 2-year observation period
      appears to be less frequent than previously reported in stroke patients on
      antiplatelet agents after the acute phase, which could be due to the adequate
      control of risk factors, and because patients with stroke within 2 weeks after
      the onset were excluded. The results of the CATHARSIS trial suggest a potential
      utility of pharmacotherapies with cilostazol plus aspirin as well as of strict
      control of risk factors for the management of symptomatic IAS. Larger studies
      with higher statistical power are required to obtain conclusive results.

PMID- 25759710
TI  - Erratum.
AB  - [This corrects the article DOI: 10.1159/000369294.]. 

PMID- 25759709
TI  - Accuracy of reporting the hyperdense middle cerebral artery sign as a function of
      clinical experience.
AB  - BACKGROUND/AIM: The hyperdense middle cerebral artery sign (HMCAS) is a useful
      clinical sign in the management of acute stroke and may alter time-critical
      decisions within an emergency setting. Though gold standards have been published,
      these are rarely used in clinical practice and scans tend to be reported
      subjectively. It is therefore possible that the level of experience of the doctor
      reporting the scan may impact on the accuracy of the reporting and hence patient
      management. This study was designed to evaluate the accuracy in detecting HMCAS
      across doctors with varying levels of experience. METHODS: Forty doctors were
      recruited into four categories of experience. Each subject received a brief
      computer-based tutorial on how to identify an HMCAS and was then asked to report
      on the presence or absence of an HMCAS in 19 pre-prepared CT scans using a
      standardised viewing template. RESULTS: The mean (+/-SE) percentage correct
      scores increased with experience from 76.8 +/- 3.69 among interns and residents
      to 90.1 +/- 2.23 (neurologists and radiologists; p < 0.01). Sensitivity and
      specificity as well as positive and negative predictive values all increased with
      experience. In addition, more experienced clinicians were better able to
      distinguish scans which met the radiological criteria for HMCAS from those which
      only just failed to do so. CONCLUSIONS: Experienced neurologists and radiologists
      consistently and accurately reported the presence or absence of HMCAS, whereas
      less experienced clinicians tended to over-report the presence of HMCAS. This may
      have implications for the acute management of thromboembolic stroke.

PMID- 25759711
TI  - Persistence and Prognostic Implications of Orthostatic Hypotension in Older
      Individuals with Mild-to-Moderate Dementia.
AB  - AIM: To study the course and prognostic implications of orthostatic hypotension
      (OH) in older individuals with mild-to-moderate dementia. METHODS: Referrals to
      outpatient clinics specialising in old age psychiatry and geriatric medicine in
      the counties of Rogaland and Hordaland in western Norway with a first-time
      diagnosis of mild dementia were consecutively asked for inclusion. A total of 211
      participants underwent a comprehensive baseline assessment with annual follow
      ups. Patients with OH at both baseline and the 1-year follow-up were classified
      as having persistent OH. Outcome measures were the Mini-Mental State Examination
      (MMSE), the Clinical Dementia Rating sum of boxes (CDR-SB), and time to death.
      RESULTS: From baseline to the 4-year follow-up, 30-45% of the participants had OH
      at each follow-up. In multivariable analysis, persistent OH was not significantly
      associated with either the longitudinal course of MMSE or CDR-SB scores or
      survival. CONCLUSIONS: OH was moderately prevalent over 4 years in older
      individuals with mild dementia, and persistent OH did not predict either
      cognitive or functional decline or survival.

PMID- 25759712
TI  - An Investigation of the Late Excitatory Potentials in the Hand following
      Transcranial Magnetic Stimulation in Early Alzheimer's Disease.
AB  - BACKGROUND: Recent neuroimaging studies in humans support the clinical
      observations that the motor cortex is affected early in the course of Alzheimer's
      disease (AD). PATIENTS AND METHODS: We measured the silent period (SP) induced by
      transcranial magnetic stimulation in AD patients in the very early stage of the
      disease, and we explored whether and in which way the pharmacologic manipulation
      of the cholinergic system could modify it. RESULTS: An increase in the duration
      of the SP was observed in AD patients in the early stage in comparison to
      controls. After 2 months of treatment with donepezil, the duration did not differ
      significantly from that of normal subjects. The results of our study show a
      fragmentation and an enlargement of the SP in the presence of multiple late
      excitatory potentials (LEPs) in early untreated AD patients. These LEPs were also
      modulated by donepezil. CONCLUSIONS: The results suggest an early functional
      impairment of cholinergic neurotransmission in AD. The disturbance in
      acetylcholine output in early AD leads to a decrease in excitability of the motor
      system.

PMID- 25759713
TI  - Anosognosia and anosodiaphoria in mild cognitive impairment and Alzheimer's
      disease.
AB  - AIMS: To evaluate the occurrence of anosognosia (lack of awareness) and
      anosodiaphoria (insouciance) in mild cognitive impairment (MCI) and Alzheimer's
      disease (AD) and to evaluate the influence of a worsening of dementia on these
      phenomena. METHODS: A self-evaluation scale was used assessing degrees of
      anosognosia and anosodiaphoria; furthermore, a neuropsychological assessment and
      statistical analyses with nonparametric tests which could cope with data on an
      ordinal scale level and small samples were employed. RESULTS: Cognitive ability
      was lower in AD (n = 9) than in MCI patients (n = 12), but AD patients self-rated
      lower cognitive disabilities, which is interpreted as one relative sign of
      anosognosia in AD. Awareness of the reasons for cognitive problems was also lower
      in AD, which is considered as another sign of anosognosia. The main pattern in
      MCI found that the higher the awareness, the lower the cognitive ability. In AD
      low awareness paralleled low cognitive functioning. Anosodiaphoria was present in
      AD but not in MCI. CONCLUSION: According to the literature anosognosia and
      anosodiaphoria seem to increase with progression of dementia from MCI as a result
      of right hemispheric alterations.

PMID- 25759714
TI  - Scene categorization in Alzheimer's disease: a saccadic choice task.
AB  - AIMS: We investigated the performance in scene categorization of patients with
      Alzheimer's disease (AD) using a saccadic choice task. METHOD: 24 patients with
      mild AD, 28 age-matched controls and 26 young people participated in the study.
      The participants were presented pairs of coloured photographs and were asked to
      make a saccadic eye movement to the picture corresponding to the target scene
      (natural vs. urban, indoor vs. outdoor). RESULTS: The patients' performance did
      not differ from chance for natural scenes. Differences between young and older
      controls and patients with AD were found in accuracy but not saccadic latency.
      CONCLUSIONS: The results are interpreted in terms of cerebral reorganization in
      the prefrontal and temporo-occipital cortex of patients with AD, but also in
      terms of impaired processing of visual global properties of scenes.

PMID- 25759716
TI  - Cognitive assessment of elderly inpatients: a clinical audit.
AB  - BACKGROUND: Comprehensive geriatric assessment including cognitive assessment
      results in better outcomes and quality of life through facilitating access to
      support and further care. The National Audit of Dementia Care revealed too few
      patients were being assessed for cognition and therefore failing to receive
      adequate care. METHODS: This was a retrospective clinical audit in a district
      general hospital with systematic sampling of the clinical records of 50
      inpatients on an elderly care ward. A descriptive analysis of the results was
      performed. RESULTS: Despite guidance that cognitive assessment should be
      performed on admission, this was only documented in 22% of the medical notes.
      However, this rate improved to 56% by discharge. The most commonly used tool was
      the Abbreviated Mental Test (AMT) 10. Assessment completion was independent of
      gender or social support, but only patients aged over 75 years were assessed. Of
      those, 75% had some level of cognitive impairment and 36.8% received a new or
      suspected diagnosis of dementia. DISCUSSION: Cognitive assessment rates continue
      to be low. Our findings support the need for increased education regarding the
      importance and benefits of assessment as well as how to complete and document the
      assessment correctly. CONCLUSION: Cognitive assessment rates need to be further
      improved to promote better outcomes for patients with dementia.

PMID- 25759715
TI  - Aerobic physical exercise improved the cognitive function of elderly males but
      did not modify their blood homocysteine levels.
AB  - BACKGROUND: Physical exercise influences homocysteine (Hcy) concentrations,
      cognitive function and the metabolic profile. The purpose of this study was to
      investigate the influence of regular physical exercise on Hcy levels, the
      metabolic profile and cognitive function in healthy elderly males before and
      after an endurance exercise program. METHODS: Forty-five healthy and sedentary
      volunteers were randomized into 2 groups: (1) a control group asked not to change
      their normal everyday activities and not to start any regular physical exercise
      program and (2) an experimental group trained at a heart rate intensity
      corresponding to ventilatory threshold 1 (VT-1) for 60 min/day 3 times weekly on
      alternate days for 6 months using a cycle ergometer. All volunteers underwent
      cognitive evaluations, blood sample analyses and ergospirometric assessments.
      RESULTS: A significant improvement in cognitive function was observed in the
      experimental group compared with the control group (p < 0.05). No significant
      changes in Hcy levels were observed in the experimental group (p > 0.05), but
      there was a significant increase in peak oxygen consumption and workload at VT-1
      as well as a significant improvement in cholesterol, triglycerides, HDL, glucose,
      alkaline phosphatase, urea, T3, T4 and prostate-specific antigen compared with
      the control group (p < 0.05). CONCLUSION: The data suggest that a physical
      exercise program does not reduce Hcy levels in healthy elderly males, although it
      improves the cardiovascular and metabolic profile as well as cognitive function.

PMID- 25759718
TI  - Corrigendum to: The establishment of Central American migratory corridors and the
      biogeographic origins of seasonally dry tropical forests in Mexico.
AB  - [This corrects the article on p. 433 in vol. 5, PMID: 25566320.]. 

PMID- 25759719
TI  - Assessing the effects of multiple markers in genetic association studies.

PMID- 25759717
TI  - Epigenetics as an answer to Darwin's "special difficulty," Part 2: natural
      selection of metastable epialleles in honeybee castes.
AB  - In a recent perspective in this journal, Herb (2014) discussed how epigenetics is
      a possible mechanism to circumvent Charles Darwin's "special difficulty" in using
      natural selection to explain the existence of the sterile-fertile dimorphism in
      eusocial insects. Darwin's classic book "On the Origin of Species by Means of
      Natural Selection" explains how natural selection of the fittest individuals in a
      population can allow a species to adapt to a novel or changing environment.
      However, in bees and other eusocial insects, such as ants and termites, there
      exist two or more castes of genetically similar females, from fertile queens to
      multiple sub-castes of sterile workers, with vastly different phenotypes,
      lifespans, and behaviors. This necessitates the selection of groups (or kin)
      rather than individuals in the evolution of honeybee hives, but group and kin
      selection theories of evolution are controversial and mechanistically uncertain.
      Also, group selection would seem to be prohibitively inefficient because the
      effective population size of a colony is reduced from thousands to a single
      breeding queen. In this follow-up perspective, we elaborate on possible
      mechanisms for how a combination of both epigenetics, specifically, the selection
      of metastable epialleles, and genetics, the selection of mutations generated by
      the selected metastable epialleles, allows for a combined means for selection
      amongst the fertile members of a species to increase colony fitness. This "intra
      caste evolution" hypothesis is a variation of the epigenetic directed genetic
      error hypothesis, which proposes that selected metastable epialleles increase
      genetic variability by directing mutations specifically to the epialleles.
      Natural selection of random metastable epialleles followed by a second round of
      natural selection of random mutations generated by the metastable epialleles
      would allow a way around the small effective population size of eusocial insects.

PMID- 25759720
TI  - Study on the calculation models of bus delay at bays using queueing theory and
      Markov chain.
AB  - Traffic congestion at bus bays has decreased the service efficiency of public
      transit seriously in China, so it is crucial to systematically study its theory
      and methods. However, the existing studies lack theoretical model on computing
      efficiency. Therefore, the calculation models of bus delay at bays are studied.
      Firstly, the process that buses are delayed at bays is analyzed, and it was found
      that the delay can be divided into entering delay and exiting delay. Secondly,
      the queueing models of bus bays are formed, and the equilibrium distribution
      functions are proposed by applying the embedded Markov chain to the traditional
      model of queuing theory in the steady state; then the calculation models of
      entering delay are derived at bays. Thirdly, the exiting delay is studied by
      using the queueing theory and the gap acceptance theory. Finally, the proposed
      models are validated using field-measured data, and then the influencing factors
      are discussed. With these models the delay is easily assessed knowing the
      characteristics of the dwell time distribution and traffic volume at the curb
      lane in different locations and different periods. It can provide basis for the
      efficiency evaluation of bus bays. 

PMID- 25759721
TI  - Clinical and Oncological Value of Preoperative BMI in Gastric Cancer Patients: A
      Single Center Experience.
AB  - Introduction. The impact of preoperative BMI on surgical outcomes and long-term
      survival of gastric cancer patients was investigated in various reports with
      contrasting results. Materials & Methods. A total of 378 patients who underwent a
      surgical resection for primary gastric cancer between 1994 and 2011 were
      retrospectively studied. Patients were stratified according to BMI into a normal
      group (<25, group A), an overweight group (25-30, group B), and an obesity group
      (>=30, group C). These 3 groups were compared according to clinical-pathological
      characteristics, surgical treatment, and long-term survival. Results. No
      significant correlations between BMI and TNM (2010), UICC stage (2010), Lauren's
      histological type, surgical results, lymph node dissection, and postoperative
      morbidity and mortality were observed. Factors related to higher BMI were male
      gender (P < 0.05), diabetes (P < 0.001), and serum blood proteins (P < 0.01). A
      trend to fewer lymph nodes retrieved during gastrectomy with lymphadenectomy in
      overweight patients (B and C groups) was observed, although not statistically
      significant. There was no difference in overall survival or disease-specific
      survival between the three groups. Conclusion. According to our data, BMI should
      not be considered a significant predictor of postoperative complications or long
      term result in gastric cancer patients. 

PMID- 25759722
TI  - Short-term relationship between hip fracture and weather conditions in two
      Spanish health areas with different climates.
AB  - OBJECTIVE: To evaluate differences in the short-term relationship between weather
      conditions and the incidence of hip fracture in people aged 65 and over among two
      regions of Spain. METHODS: Hip fracture incidence was calculated for the years
      2000-2008 for residents of Health Area 14 in Valencian Community (Mediterranean
      climate) and the "Mancha Centro" Health Area in Castilla-La Mancha (inland
      climate), Spain. The relationship between hip fracture incidence and weather was
      analyzed with a case-crossover design and explored in subgroups defined by sex,
      age, and fracture type. RESULTS: In the inland area, a positive and significant
      tendency for hip fracture incidence was observed (annual increase: 1.5%) whereas
      in the Mediterranean area a seasonal increase of 9% was noted in autumn and
      winter with respect to spring. Weather conditions, especially wind, were
      significantly associated with hip fracture incidence: days with more frequent
      windy periods and/or a greater wind velocity were associated with an increase in
      hip fracture incidence of 51% in the Mediterranean area and 44% in the inland
      area. CONCLUSIONS: Hip fracture incidence exhibits seasonal changes that differ
      between the Mediterranean and inland areas. The short-term relationship with
      climate, although similar in both areas, may partly explain these seasonal
      changes.

PMID- 25759723
TI  - Comparative assessment of blood lead levels of automobile technicians in
      organised and roadside garages in Lagos, Nigeria.
AB  - Occupational exposure to lead is common among automobile technicians and
      constitutes 0.9% of total global health burden with a majority of cases in
      developing countries. The aim of this study was to determine and compare the
      blood lead levels of automobile technicians in roadside and organised garages in
      Lagos State, Nigeria. This was a comparative cross-sectional study. Data were
      collected using interviewer-administered questionnaires. Physical examinations
      were conducted and blood was analysed for lead using atomic spectrophotometery.
      Statistical analyses were performed to compare the median blood lead levels of
      each group using the independent sample (Mann-Whitney U) test. Seventy-three
      (40.3%) of the organised compared to 59 (34.3%) of the roadside groups had high
      blood lead levels. The organised group had statistically significant higher
      median blood lead levels of, 66.0 ug/dL than the roadside 43.5 ug/dL (P < 0.05).
      There was also statistically significant association between high blood lead
      levels and abnormal discolouration of the mucosa of the mouth in the organised
      group. Automobile technicians in organised garages in Lagos have higher
      prevalence of elevated blood lead levels and higher median levels than the
      roadside group. Preventive strategies against lead exposures should be instituted
      by the employers and further actions should be taken to minimize exposures,
      improve work practices, implement engineering controls (e.g., proper
      ventilation), and ensure the use of personal protective equipment. 

PMID- 25759724
TI  - Comparison of three staining methods for the detection of intestinal microspora
      spp.
AB  - BACKGROUND: This study aimed to compare three staining methods including:
      Calcofluor white, Chromotrope and Quick Hot Gram chromotrope used in diagnosis of
      intestinal microsporidial spores. METHODS: One hundred and seventy five stool
      specimens were collected from patients referred to Laboratory of Intestinal
      Protozoology at the School of Public Health, Tehran University of Medical
      Sciences during 2012-2013. All of specimens were evaluated by nested PCR. The
      formalin-fixed stool samples were prepared from each specimen and dried at room
      temperature for 10 min, followed by 10 min methanol fixation. All the collected
      stool samples were evaluated blindly by calcofluor white, Chromotrope and Quick
      Hot Gram chromotrope staining methods separately. RESULTS: Microsporidial spores
      were recognized using Chromotrope, Quick Hot Gram chromotrope and Calcofluor
      white, in16 of 18 (88.8%), 17 of 18 (94.4%) and 18 of 18(100%) samples that were
      positive by nested PCR respectively. Regarding 14 stool samples that were
      negative by nested PCR, 14 cases were negative by chromotrope and Quick hot Gram
      chromotrope and 13 samples were negative by Calcofluor white. One discordant
      sample interpreted as false positive. CONCLUSION: Calcofluor white staining had
      the best performance for the detection of intestinal Microsprora spores and can
      be used as initial screen test for the detection of intestinal Microspora spp.

PMID- 25759725
TI  - In Vitro Study of Leishmanicidal Activity of Biogenic Selenium Nanoparticles
      against Iranian Isolate of Sensitive and Glucantime-Resistant Leishmania tropica.
AB  - BACKGROUND: Sensitive and glucantime (MA) resistance Leishmania tropica are
      referred to those isolates, which are responsive, or non-responsive to one or two
      full courses of treatment by MA systematically and/or intra-lesionally,
      respectively. In this study, we evaluated the antileishmanial activity of
      biogenic selenium nanoparticles (Se NPs) alone and in combination with MA against
      sensitive and glucantime-resistant L. tropica on in vitro model. METHODS: The Se
      NPs were synthesized by employing the Bacillus sp. MSh-1. The antileishmanial
      effects of Se NPs alone and in combination with MA on promastigote and amastigote
      stages of sensitive and glucantime-resistant L. tropica strains have been
      investigated using a colorimetric MTT assay and in a macrophage model. In
      addition hemolytic activity in type O+ human red blood cells and infectivity rate
      of the promastigotes before and after treatment with the Se NPs was evaluated.
      RESULTS: In the promastigote stage, various concentrations of Se NPs
      significantly inhibited (P<0.05) the growth of promastigotes of both strains in a
      dose-dependent manner. Similarly, Se NPs especially in combination with MA
      significantly reduced the mean number of amastigotes of both strains in each
      macrophage. Se NPs showed no hemolytic effect on human RBCs at low
      concentrations. Moreover, infection rate of macrophages by promastigotes
      significantly (P<0.05) was reduced when promastigotes pre-treated with Se NPs.
      CONCLUSION: The findings of this study suggest a first step in the search of Se
      NPs as a new antileishmanial agent. Further experiments are needed to investigate
      antileishmanial effects of biogenic Se NPs on L. tropica using a clinical
      setting.

PMID- 25759726
TI  - Seroprevalence of human fascioliasis using indirect ELISA in isfahan district,
      central iran in 2013.
AB  - BACKGROUND: The aim of this study was to detect the seroprevalence of human
      fascioliasis in Isfahan County, central Iran in 2013. METHODS: Overall, 471 sera
      samples were collected from people recalled randomly to 20 health centers in the
      city of Isfahan and 10 related villages in 2014. Sera were examined using ELISA
      test. A questionnaire was filled out for each participant. RESULTS: Altogether
      eight cases (1.7%) were seropositive which had the OD absorbance in ELISA test
      more than the calculated cutoff of 0.36. All of them were female. One positive
      subject had a history of consuming Delar (Local dish) and three seropositive
      cases with history of eating Zeitoon-Parvadeh (Proceeded olive). CONCLUSION:
      Isfahan County might be considered as one area apt for fascioliasis. More studies
      in terms of veterinary investigation and verifying the risk factors are
      necessary.

PMID- 25759727
TI  - Application of Multiplex PCR for Detection and Differentiation of Entamoeba
      histolytica, Entamoeba dispar and Entamoeba moshkovskii.
AB  - BACKGROUND: Entamoeba moshkovskii and E. dispar are impossible to differentiate
      microscopically from the pathogenic species E. histolytica. Multiplex polymerase
      chain reaction (Multiplex PCR) is a widespread molecular biology technique for
      amplification of multiple targets in a single PCR experiment. METHODS: For
      detection and differentiation of the three-microscopy indistinguishable Entamoeba
      species in human, multiplex PCR assay using different DNA extraction methods was
      studied. A conserved forward primer was derived from the middle of the small
      subunit rRNA gene, and reverse primers were designed from signature sequences
      specific to each of these three Entamoeba species. RESULTS: A 166-bp PCR product
      with E. histolytica DNA, a 580-bp product with E. moshkovskii DNA and a 752-bp
      product with E. dispar DNA were generated in a single-round and multiplex PCR
      reaction. CONCLUSION: We recommend this PCR assay as an accurate, rapid, and
      effective diagnostic method for the detection and discrimination of these three
      Entamoeba species in both routine diagnosis of amoebiasis and epidemiological
      surveys.

PMID- 25759728
TI  - Frequency of Toxoplasma gondii in HIV Positive Patients from West of Iran by
      ELISA and PCR.
AB  - BACKGROUND: Toxoplasma gondii, the obligate intracellular parasite is life
      threatening in AIDS patients. Diagnosis of toxoplasmosis is based on serological
      methods especially increasing of IgM and IgG titers, but finding of parasite or
      its components (antigenemia) may be beneficial method in order to detection of
      acute toxoplasmosis in immunocompromised patients. METHODS: Ninety-four serum
      samples from HIV positive patients were collected from Sanandaj, Kordistan west
      of Iran. These patients were lived in Sanandaj of whom 26 were prisoners infected
      with HIV virus in prison. Toxoplasma gondii antibodies were determined by IgG
      ELISA. T. gondii antigen was identified by capture-ELISA. PCR was performed on
      samples with T. gondii antigenemia. CD4+ T cells counts had been determined by
      flowcytometry and were obtained from records of each patient. RESULTS: Among the
      examined HIV seropositive individuals, 19.1% (18/94) and 5.3% (5/94) were
      positive for Toxoplasma-IgG and antigenemia, respectively. Besides, one of the
      samples was positively detected by PCR method. Mean age of participants was 37.9
      +/- 9.5 year. Prevalence of IgG antibody and antgenemia was higher in age group
      of 40-50 years old. The Mean of CD4+ T cells counts of participants (total of
      HIV+ patients, IgG positive patients and patients with antigenemia) was 699.2 +/-
      345.2, 655.1 +/- 237.9 and 620.2 +/- 215.1 respectively. CONCLUSION: Capture
      ELISA and PCR could confirm the T. gondii acute infection in HIV positive
      patients. For precise diagnosis of acute toxoplasmosis in HIV positive patient,
      performance of more studies based on more sensitive types of PCR is suggested.

PMID- 25759729
TI  - Isolation of Small Number of Cryptosporidium parvum Oocyst Using
      Immunochromatography.
AB  - BACKGROUND: Cryptosporidium parvum causes severe gastroenteritis in
      immunocompromised human and new borne animals. The organism can be transmitted
      through water. Since small number of C. parvum is infectious, the aim of the
      present study was to develop a chromatography method for the isolation of C.
      parvum oocyst in samples with limited number of oocysts. METHODS: Antibody was
      prepared against whole antigen from C. parvum oocysts, the achieved Ab bound to
      the sepharose 4B and used for the isolation of oocysts. Antibody against P23
      bound to the sepharose 4B, used also for the isolation of C. parvum oocyst. In
      comparison to these both methods, 2 traditional methods (Salt floatation and 55%
      sucrose floatation) were also performed. RESULTS: Both chromatography methods
      could bind oocysts with capacity depends on the column size. The isolated oocysts
      were free of bacteria. Our results showed that the traditional methods are useful
      for the isolation of oocysts from feces, in its smear stained with ziehl-nelsen,
      at least 3 oocyts are detectable in each microscopic field under 1000 X
      magnification. In contrast to the chromatography methods, the bacterial
      contamination was always observed in oocysts isolated with traditional methods.
      CONCLUSION: Immunochromatography could be used for the successful isolation of C.
      parvum oocysts from the samples containing limited number of oocysts.

PMID- 25759730
TI  - Evaluation of Immunogenicity of Novel Isoform of EG95 (EG95-5G1) From
      Echinococcus granulosus in BALB/C Mice.
AB  - BACKGROUND: Echinococcosis is a zoonotic parasitic disease of humans and various
      herbivorous domestic animals transmitted by the contact with domestic and wild
      carnivores, mainly dogs and foxes. The aim of this study is the production,
      purification and evaluation immunogenicity of new construction of EG95 protein.
      METHODS: The recombinant plasmid pET32-a+ used for Eg95 expression was
      constructed with the EG95 gene of Echinococcus granulosus fused with the
      thioredoxin tag. This recombinant clone was over expressed in Escherichia coli BL
      21 (DE-3). The expressed fusion protein was found almost entirely in the
      insoluble form (inclusion bodies) in cell lysate. The purification was performed
      under denaturing conditions in the presence of 8M urea by Ni-NTA column and
      dialysis. The purified recombinant proteins were confirmed with western blot
      analysis using polyclonal antiserum. To find out the immunogenicity of the
      purified protein, the BALB/c mice (10 mice/group) were immunized by injecting 20
      MUg rEG95 protein formulated in Freund's and alum adjuvant. RESULTS: Immunization
      of mice with rEG95 using CFA/IFA and alum adjuvant generated high level of total
      antibody. In proliferation assay, the lymphocytes were able to mount a strong
      proliferative response with related production of IFN-gamma, IL-12 and TNF-alpha
      but with low secretion of either IL-4 or IL-10. The humoral and cellular immune
      responses against rEG95 suggested a mixed Th1/Th2 response with high intensity
      toward Th1. CONCLUSION: Our findings suggest that new construct of rEG95
      formulated with CFA/IFA and alum adjuvant elicited strong cellular and humoral
      responses supporting further development of this vaccine candidate.

PMID- 25759732
TI  - Helminth Infections of House Mouse (Mus musulus) and Wood Mouse (Apodemus
      sylvaticus) from the Suburban Areas of Hamadan City, Western Iran.
AB  - BACKGROUND: To determine the prevalence and intensity of helminths and their
      zoonotic importance in small rodents inhabiting in the suburban areas of Hamadan
      City, Iran. METHODS: The present survey was conducted on the helminth infections
      of two species of rodents Apodemus sylvaticus (n=60) and Mus musculus(n=72) in
      the suburban areas of Hamadan City during 2010-2012. Rodents were collected and
      examined for helminth in the different organs. The nematodes were collected in 5%
      formalin solution and cleared in lactophenol, cestodes and trematodes collected
      from intestine fixed in AFA solution and stained by acetocarmine, cleared in
      xylol for identification. RESULTS: Helminths found in A. sylvaticus and M.
      musculus and their prevalence for the first time in suburban areas of Hamadan
      City were as follows; In A. sylvaticus: Cysticercus fasciolaris(3.33%), Syphacia
      fredrici(26.67%), S. stroma(8.33%), Anoplocephalidae sp. (1.67%), Skrjabinotaenia
      lobata(5%), Plagiorchis muris(1.67%) and in M. musculus:Hymenolepis nana
      (16.67%), H.diminuta (5.55%), S. obvelata(30.56%), S. ohtarom (9.72%),
      Rodentolepis crassa (1.39%), C. fasciolaris (1.39%). Among 11 species in two
      rodents 4 species including S. obvelata, H. nana, H.diminuta,and P. muris have
      zoonotic importance. Statistically the relation between gender and their helminth
      infections was not significant in either M. musculus or A. sylvaticus (P>0.05).
      CONCLUSION: This study reports 11 species of helminths and on the other hand 3
      species were identified for the first time in Iran and 5 species of them have
      potential health importance for public health and cat.

PMID- 25759731
TI  - Protoscolecidal Effect of Berberis vulgaris Root Extract and Its Main Compound,
      Berberine in Cystic Echinococcosis.
AB  - BACKGROUND: Cystic echinococcosis (CE), a zoonotic parasitic infection caused by
      the metacestode (larvae) stage of dog tapeworm Echinococcus granulosus and
      recognized as a major economic and public health concern in the world. This study
      aimed to investigate the in vitro scolicidal effect of methanolic extract of
      Berberis vulgaris L. roots and its main compound, berberine against protoscoleces
      of hydatid cysts. METHODS: For this purpose, protoscoleces were aseptically
      aspirated from sheep livers having hydatid cysts. Various concentrations of the
      methanolic extract (0.25-2 mg/ml) and berberine (0.062- 0.5 mg/ml) were used for
      5 to 30 min. Viability of protoscoleces was confirmed by eosin exclusive test.
      RESULTS: In the present study, all of the various concentrations of the B.
      vulgaris methanolic extract (0.25, 0.5, 1 and 2 mg/ml) and berberine (0.062,
      0.125, 0.25 and 0.5 mg/ml) revealed significant (P<0.05) scolicidal effects
      against protoscoleces of E. granulosus in a dose-dependent manner. Both berberine
      and methanolic extract exhibited 100% inhibition against protoscoleces of E.
      granulosus at the concentration of 2.0 and 0.5 mg/ml after 10 min incubation,
      respectively. CONCLUSION: According to the results, both B. vulgaris methanolic
      extract and berberine alone demonstrated high scolicidal activities against
      protoscoleces of hydatid cysts in low concentration and short exposure time on in
      vitro model. However, in vivo efficacy of B. vulgaris and berberine also requires
      to be evaluated using an animal model with hydatid infection.

PMID- 25759733
TI  - Epidemiological and diagnostic features of blastocystis infection in symptomatic
      patients in izmir province, Turkey.
AB  - BACKGROUND: The aims of this study were to identify Blastocystis subtypes (STs)
      in a cohort of Turkish patients with various gastrointestinal symptoms using a
      novel Real Time PCR method developed recently for Blastocystis detection and
      assess the relationship between Blastocystis STs and patient symptoms. METHODS:
      Totally, 617 stool samples of patients with gastrointestinal symptoms were
      examined with microscopy and inoculated in Jones medium. Blastocystis-positive
      samples were further assessed to identify coinfections with other possible
      pathogens, including bacteria and viruses. Diagnostic efficacies of microscopy,
      culture and Real-Time PCR were compared. PCR products were sequenced to identify
      the subtypes of Blastocystis isolates. RESULTS: Totally 94 (15.24%) samples were
      positive for Blastocystis after all methods. Among these, 83 of 94 (88.3%)
      samples were identified with all methods, while 11 were positive only with Real
      Time PCR. Diarrhea and abdominal pain were the leading symptoms in the patients.
      The only pathogenic agent identified in 76 of 94 (80.9%) patients was
      Blastocystis. Subtype 3 was the leading Blastocystis subtype (44.6%), while
      subtypes 6 and 7 were firstly isolated from symptomatic patients in our region.
      CONCLUSION: Comparison of three diagnostic methods indicated Real Time PCR as the
      most sensitive and specific method. Blastocystis was the only pathogenic agent
      among symptomatic patients, with subtype 3 being predominant. Patients with
      subtypes 6 and 7 need further assessments concerning the zoonotic potential of
      Blastocystis.

PMID- 25759734
TI  - Ginger and cinnamon: can this household remedy treat giardiasis? Parasitological
      and histopathological studies.
AB  - BACKGROUND: Giardia lamblia is one of the most common protozoal infections in
      human especially children. Metronidazol (MTZ) is the drug of choice for treatment
      of giardiasis; its chemical composition possesses major threats and is becoming
      less sensitive. This study aimed to search for natural extracts alternative to
      MTZ. METHODS: In-vivo effects of dichloromethane extracts of ginger and cinnamon
      in doses of 10 and 20 mg/kg/day separately were studied on 30 experimentally
      infected albino rats divided into 6 groups (5 rats each). Plant extracts were
      started on the 6th day post infection for 7 successive days. The study was
      evaluated by fecal cyst and intestinal trophozoite counts, histopathology,
      scanning and transmission electron microscopic examinations of the small
      intestinal mucosa. RESULTS: Ginger and cinnamon caused reduction of fecal cyst
      and trophozoites counts. Histopathology, scanning electron microscopy (SEM) and
      transmission electron microscopy (TEM) after exposure to each extract revealed
      evident improvement of intestinal mucosal damage produced by G. lamblia infection
      and direct structural injury to the trophozoites. However, these results were
      more obvious after exposure to cinnamon extracts. CONCLUSION: We confirmed the
      potential therapeutic effects of ginger and cinnamon extracts on G. lamblia
      infection in albino rats as a promising alternative therapy to the commonly used
      antigiardial drugs.

PMID- 25759735
TI  - Incidence of Giardia lamblia Subspecies by PCR-RFLP in Stool Specimens of
      Hospitalized Children at Urmia Mutahhari Hospital, West Azerbaijan Province,
      Iran.
AB  - BACKGROUND: Giardia lamblia is one of the most prevalent intestinal flagellate
      protozoa that infects a wide range of vertebrate hosts causing severe intestinal
      disorder in children.This study was performed to determine subspecies of
      G.lamblia by the PCR-RFLP method, targeting the glutamate
      dehydrogenase(gdh)locus, in hospitalized children at Urmia Mutahhari Hospital,
      West Azerbaijan Province,Iran and determining the infection transformational
      storages in this area. METHODS: Overall, 720 stool specimens were collected from
      the hospitalized children, 34 samples were positive and Giardia cysts were
      detected under the microscope. Cysts were partially purified by the sucrose
      density gradient method and then washed with sterile distilled water to remove
      effectively the PCR inhibitors. Genomic DNA of G. lamblia isolates was extracted
      by freeze-thaw cycles followed by phenol/ chloroform/isoamyl alcohol method. The
      single step PCR-RFLP assay was used to differentiate the assemblages between A
      and B, which were found in humans. In this method, 432 bp expected size was
      amplified, and then for detection of subspecies, specific restriction RsaI and
      BspLI enzymes were used. RESULTS: Totally 34 samples were positive in terms of
      Giardia cyst out of 720 examined samples microscopically, so the parasite spread
      rate is reported 4.72%. Analysis PCR-RFLP on these samples revealed that 28
      samples (93.3%) have the genotype BIII and 2 samples (6.7%) belong to the
      subgroup BIV. CONCLUSION: PCR-RFLP is a proper analytical method for determining
      the genotype among parasite types, using the glutamate dehydrogenizes zone's
      genes. Based on the results, an animal origin of infection cycle is suggested.

PMID- 25759736
TI  - Helminth Infections in Rattus ratus and Rattus norvigicus in Tehran, Iran.
AB  - BACKGROUND: The aim of this study was to determine intestinal and liver helminth
      infections in Rattus rodents in Tehran Iran. METHODS: Overall, 306 traps were put
      in 39 different regions in Tehran from 2009 to 2010. Rodents, including R. rattus
      and R. norvegicus were caught by live-traps. They become unconscious and the
      spinal cords were cut, afterwards the body was dissected and the stomach, small
      intestine, large intestine, liver, and cecum were studied separately. The
      dominant type and the prevalence rate of parasites in the rodents were determined
      based on the infected parts of their body. RESULTS: After recognition of the
      helminthes' types, among the 120 total number of rodents, 39 belonged to males,
      while among the infected rodents, 57(47.5%) were female and 18(15%) were male.
      The prevalence of infection in Tehran was 62.5%. Seventy cases (58.33%) of
      helminth infections were observed in R. rattus and 5 cases (4.16%) were observed
      in R. norvegicus. The maximum prevalence (15.5%) was seen in the center and east
      part of Tehran, while the minimum (9.16%) was in the north part of the city. The
      helminthes types and the corresponding percentages were Hymenolepis nana fraterna
      (35.8%), Heterakis spumosa (17.5%), Hymenolepis diminuta (7.5%) and Capillaria
      annulosa (1.6%). The dominant rodent was Rattus rattus and among the identified
      helminthes, Hymenolepis diminuta and Hymenolepis nana fraterna are zoonotic ones.
      CONCLUSION: The information presented here improves our understanding of the
      major parasitic infections that rodents harbor and can transmit to human and
      animal populations in Iran. To prevent infectivity of human, the hazard of the
      identified zoonotic species needs to be contemplated.

PMID- 25759737
TI  - Herbal Remedies Connected to Malaria like Fever in Iranian Ancient Medicinal
      Books- Brief Review Article.
AB  - Malaria is a major international public health problem. Drug-resistant parasites
      have made treatment and control of malaria more difficult. Therefore, safe,
      affordable and effective new drugs are urgently needed. Traditional medicine is
      an important source for new drugs. Determining the ancient medicinal books was
      the first step of this study for finding malaria or disease that has symptoms
      like malaria. Then the plants that used to treat "Ghebbe Khalesseh fever" were
      listed. Finally, recent antimalarial researches were explored. About 31 plants
      were identified. Information from these resources is valuable for the selection
      of plants for antiplasmodial screening programs. 

PMID- 25759738
TI  - Canine Heartworm in Southeastern of Iran with Review of disease distribution.
AB  - BACKGROUND: Heartworm (Dirofilaria immitis) is mosquito-borne filarial nematode
      capable of causing serious cardiopulmonary disease in canines and felines, and
      pulmonary dirofilariasis in man. This research was conducted with the objectives
      of determining the incidence and assessing possible risk factors of canine
      heartworm in the southeast of Iran. METHODS: From October 2012 to September 2013,
      blood samples from 87 dogs from Zabol area in Sistan and Baluchestan and 33 dogs
      from Bam area in Kerman Province were examined for detection of Dirofilaria
      immitis using modified knott test and serology. RESULTS: Out of 120 dogs, 29
      (24.2%; 95%CI: 16.6-31.8%) were positive, serologically. The overall
      seroprevalence of D. immitis in dog in Zabol and Bam was 27.5% (95% CI: 24.7
      32.5%) and 15.15% (95% CI: 12.3-20.7%), respectively. 28.8% of stray dogs and
      20.6% of housed dogs in the study areas were seropositive. Seroprevalence of D.
      immitis was not significantly different between stray and housed dogs (P =
      0.295). Investigation of seasonal dynamic of infection with D. immitis in stray
      and housed dog showed that the proportion of infected dog in spring and summer
      was greater than colder season (autumn and winter) which was not significant. The
      prevalence of infection with D. immitis in >5 years old stray dogs (53.8%) was
      greater than other age categories while in housed dogs infection rate was greater
      in 3-5 years old (27.3%). CONCLUSION: It is important to point out the increased
      incidence of canine heatrworm in Iran. In order to stop the spread of canine
      heartworm, preventive measures must be taken now.

PMID- 25759739
TI  - Preliminary Analysis of Taenia multiceps Metacestode Antigens by Two-Dimensional
      Electrophoresis.
AB  - BACKGROUND: Taenia multiceps is a cestode parasite with its larval stage
      (metacestode), Coenurus cerebralis, mainly encysts in the central nervous system
      of sheep and other livestock causing cerebralis coenurosis. Since, treatment of
      coenurosis with chemotherapy showed little effect and surgical removal of cysts
      is not advisable in field conditions, vaccination is useful to control
      coenurosis. Previous study indicated that immunization with T. multiceps
      metacestode antigens could induce protection in sheep against coenurosis, so the
      aim of this study was to identify T. multiceps metacestode antigens in order to
      find potential vaccine development candidates for further study. METHODS: The
      protein extracts from the larval T. multiceps were analyzed by two-dimensional
      electrophoresis (2-DE) and characterized by mass spectrometry. RESULTS: A total
      of 150 protein spots were detected with isoelectric point (pI) value from 4.97 to
      9.65 and molecular weight from 14 to 98 kDa. Twenty-two protein identities were
      determined by mass spectrometry and 15 unique proteins were obtained. Functional
      annotation revealed that some of these proteins are involved in catalytic
      activity, binding, metabolic, cellular process and stress response. Among these
      molecules are antioxidant proteins (peroxiredoxin and glutathione-S-transferase),
      glycolytic enzymes (malate dehydrogenase and enolase), proteins with chaperone
      activity (heat shock protein 70 and small heat shock protein), and structural
      proteins (actin, actin modulator protein and paramyosin). CONCLUSION: The
      identification of T. multiceps metacestode protein will provide valuable
      information to elucidate their specific roles in the parasitism and screen new
      targets for vaccine development.

PMID- 25759740
TI  - Sequencing and Gene Expression Analysis of Leishmania tropica LACK Gene.
AB  - BACKGROUND: Leishmania Homologue of receptors for Activated C Kinase (LACK)
      antigen is a 36-kDa protein, which provokes a very early immune response against
      Leishmania infection. There are several reports on the expression of LACK through
      different life-cycle stages of genus Leishmania, but only a few of them have
      focused on L.tropica. METHODS: The present study provides details of the cloning,
      DNA sequencing and gene expression of LACK in this parasite species. First,
      several local isolates of Leishmania parasites were typed in our laboratory using
      PCR technique to verify of Leishmania parasite species. After that, LACK gene was
      amplified and cloned into a vector for sequencing. Finally, the expression of
      this molecule in logarithmic and stationary growth phase promastigotes, as well
      as in amastigotes, was evaluated by Reverse Transcription-PCR (RT-PCR) technique.
      RESULTS: The typing result confirmed that all our local isolates belong to
      L.tropica. LACK gene sequence was determined and high similarity was observed
      with the sequences of other Leishmania species. Furthermore, the expression of
      LACK gene in both promastigotes and amastigotes forms was confirmed. CONCLUSION:
      Overall, the data set the stage for future studies of the properties and immune
      role of LACK gene products.

PMID- 25759741
TI  - Causes of pediatric visceral leishmaniasis in southeastern iran.
AB  - Leishmania infantum is the most frequent cause of visceral leishmaniasis and L.
      tropica has been rarely linked to the disease in Iran. In this study, bone marrow
      aspirates were collected from 10 child patients, suspected with visceral
      leishmaniasis referred to the Pediatric Wards of Kerman Medical Hospitals,
      Kerman, Iran during 2002-2011. Leishmania species were identified by using nested
      PCR in all slides. The PCR samples from nine patients indicated L. infantum as
      principal causative agent of visceral leishmaniasis and one L.tropica as a minor
      species. 

PMID- 25759742
TI  - Early stage of acute coenurosis in Iranian native sheep- case report.
AB  - Cerebral coenurosis is the intermediary larval stage of Taenia multiceps, which
      affects intermediate hosts, particularly sheep and goats. In this report, gross
      and microscopic features of three scarce natural coenurosis cases, a one-year-old
      ram and two lambs of 7 month old from a flock are explained. At necropsy,
      numerous small cysts measuring 5 to 10 mm in diameter were observed on both
      cerebrum and cerebellum surfaces, likewise multiple deep parts of which. In
      histopathological examination of the neural tissue, severe tissue destruction, a
      distinct layer of Gitter cells formation around the cysts, neuronophagia, gliosis
      and perivascular infiltration of lymphocytes were observed. In this early stage
      of parasite life cycle, larval migration and destruction of tissue, also
      aggregation of glial cells around the cysts cause a loose connection between
      cysts and neural tissue. 

PMID- 25759743
TI  - Human Dermatitis Caused by Ophionyssus natricis, a Snake Mite.
AB  - Ophionyssus natricis is a purely blood sucking parasite of snakes and of
      worldwide distribution. Infected snakes often exhibit lethargy, pruritus,
      crusting dermatitis, and behavioral changes. Ophionyssus natricis can also attack
      humans, causing popular vesiculo-bullous eruption of the skin. A 29 years old man
      working in zoo, Sari, Mazandaran, Iran, presented itchy papullar eruption of the
      skin. He had noticed small insects fixed on his skin and large numbers of these
      same insects on a python and its cage in the zoo. Regarding totheir morphological
      characteristics they were diagnosed as O. natricis (Geravis, 1844), a snake mite.
      It is the first report of O. natricis from Iran. 

PMID- 25759744
TI  - Toxoplasma and blood transfusion.

PMID- 25759745
TI  - Assessment of hematological, biochemical effects and genotoxicity among pesticide
      sprayers in grape garden.
AB  - BACKGROUND: Many studies revealed toxic effects of pesticides on pesticide
      handlers but very fewer studies have been reported among grape garden pesticide
      sprayers in India. The purpose of this study was to evaluate the effect of
      pesticides among grape garden sprayers. METHODS: 27 pesticide sprayers in study
      group and 27 non sprayers in control group were recruited. Blood samples were
      analyzed for hematological profile, biochemical parameters and urine samples for
      oxidative stress, buccal mucosal cells for genotoxicity. For statistical analysis
      student's t-test and Mann Whitney U test were used. RESULTS: White blood cell
      (WBC) count was significantly decreased; uric acid and Malondialdehyde (MDA)
      level was significantly increased among study group. In present study the
      Micronucleus (MN) assay for buccal mucosal cell showed significant number of
      micronucleated cells in study group. CONCLUSION: These results suggest that
      pesticide sprayers in grape garden are under risk which need to be monitored
      continuously in large population and further study is warranted to correlate the
      pesticide exposure by assessing acetylcholinesterase activity, pesticide residue
      analysis and their personal habits.

PMID- 25759746
TI  - Cognitive behavior evaluation based on physiological parameters among young
      healthy subjects with yoga as intervention.
AB  - OBJECTIVE: To investigate the effect of yoga practice on cognitive skills,
      autonomic nervous system, and heart rate variability by analyzing physiological
      parameters. METHODS: The study was conducted on 30 normal young healthy
      engineering students. They were randomly selected into two groups: yoga group and
      control group. The yoga group practiced yoga one and half hour per day for six
      days in a week, for a period of five months. RESULTS: The yoga practising group
      showed increased alpha, beta, and delta EEG band powers and significant reduction
      in theta and gamma band powers. The increased alpha and beta power can represent
      enhanced cognitive functions such as memory and concentration, and that of delta
      signifies synchronization of brain activity. The heart rate index theta/alpha
      decreased, neural activity beta/theta increased, attention resource index
      beta/(alpha + theta) increased, executive load index (delta + theta)/alpha
      decreased, and the ratio (delta + theta)/(alpha + beta) decreased. The yoga
      practice group showed improvement in heart rate variability, increased
      SDNN/RMSSD, and reduction in LF/HF ratio. CONCLUSION: Yoga practising group
      showed significant improvement in various cognitive functions, such as
      performance enhancement, neural activity, attention, and executive function. It
      also resulted in increase in the heart rate variability, parasympathetic nervous
      system activity, and balanced autonomic nervous system reactivity.

PMID- 25759747
TI  - Large-scale robot-assisted genome shuffling yields industrial Saccharomyces
      cerevisiae yeasts with increased ethanol tolerance.
AB  - BACKGROUND: During the final phases of bioethanol fermentation, yeast cells face
      high ethanol concentrations. This stress results in slower or arrested
      fermentations and limits ethanol production. Novel Saccharomyces cerevisiae
      strains with superior ethanol tolerance may therefore allow increased yield and
      efficiency. Genome shuffling has emerged as a powerful approach to rapidly
      enhance complex traits including ethanol tolerance, yet previous efforts have
      mostly relied on a mutagenized pool of a single strain, which can potentially
      limit the effectiveness. Here, we explore novel robot-assisted strategies that
      allow to shuffle the genomes of multiple parental yeasts on an unprecedented
      scale. RESULTS: Screening of 318 different yeasts for ethanol accumulation,
      sporulation efficiency, and genetic relatedness yielded eight heterothallic
      strains that served as parents for genome shuffling. In a first approach, the
      parental strains were subjected to multiple consecutive rounds of random genome
      shuffling with different selection methods, yielding several hybrids that showed
      increased ethanol tolerance. Interestingly, on average, hybrids from the first
      generation (F1) showed higher ethanol production than hybrids from the third
      generation (F3). In a second approach, we applied several successive rounds of
      robot-assisted targeted genome shuffling, yielding more than 3,000 targeted
      crosses. Hybrids selected for ethanol tolerance showed increased ethanol
      tolerance and production as compared to unselected hybrids, and F1 hybrids were
      on average superior to F3 hybrids. In total, 135 individual F1 and F3 hybrids
      were tested in small-scale very high gravity fermentations. Eight hybrids
      demonstrated superior fermentation performance over the commercial biofuel strain
      Ethanol Red, showing a 2 to 7% increase in maximal ethanol accumulation. In an 8
      l pilot-scale test, the best-performing hybrid fermented medium containing 32%
      (w/v) glucose to dryness, yielding 18.7% (v/v) ethanol with a productivity of
      0.90 g ethanol/l/h and a yield of 0.45 g ethanol/g glucose. CONCLUSIONS: We
      report the use of several different large-scale genome shuffling strategies to
      obtain novel hybrids with increased ethanol tolerance and fermentation capacity.
      Several of the novel hybrids show best-parent heterosis and outperform the
      commonly used bioethanol strain Ethanol Red, making them interesting candidate
      strains for industrial production.

PMID- 25759748
TI  - Repulsion-based model for contact angle saturation in electrowetting.
AB  - We introduce a new model for contact angle saturation phenomenon in
      electrowetting on dielectric systems. This new model attributes contact angle
      saturation to repulsion between trapped charges on the cap and base surfaces of
      the droplet in the vicinity of the three-phase contact line, which prevents these
      surfaces from converging during contact angle reduction. This repulsion-based
      saturation is similar to repulsion between charges accumulated on the surfaces of
      conducting droplets which causes the well known Coulombic fission and Taylor cone
      formation phenomena. In our model, both the droplet and dielectric coating were
      treated as lossy dielectric media (i.e., having finite electrical conductivities
      and permittivities) contrary to the more common assumption of a perfectly
      conducting droplet and perfectly insulating dielectric. We used theoretical
      analysis and numerical simulations to find actual charge distribution on droplet
      surface, calculate repulsion energy, and minimize energy of the total system as a
      function of droplet contact angle. Resulting saturation curves were in good
      agreement with previously reported experimental results. We used this proposed
      model to predict effect of changing liquid properties, such as electrical
      conductivity, and system parameters, such as thickness of the dielectric layer,
      on the saturation angle, which also matched experimental results. 

PMID- 25759749
TI  - Enhancing sensitivity and specificity in rare cell capture microdevices with
      dielectrophoresis.
AB  - The capture and subsequent analysis of rare cells, such as circulating tumor
      cells from a peripheral blood sample, has the potential to advance our
      understanding and treatment of a wide range of diseases. There is a particular
      need for high purity (i.e., high specificity) techniques to isolate these cells,
      reducing the time and cost required for single-cell genetic analyses by
      decreasing the number of contaminating cells analyzed. Previous work has shown
      that antibody-based immunocapture can be combined with dielectrophoresis (DEP) to
      differentially isolate cancer cells from leukocytes in a characterization device.
      Here, we build on that work by developing numerical simulations that identify
      microfluidic obstacle array geometries where DEP-immunocapture can be used to
      maximize the capture of target rare cells, while minimizing the capture of
      contaminating cells. We consider geometries with electrodes offset from the array
      and parallel to the fluid flow, maximizing the magnitude of the resulting
      electric field at the obstacles' leading and trailing edges, and minimizing it at
      the obstacles' shoulders. This configuration attracts cells with a positive DEP
      (pDEP) response to the leading edge, where the shear stress is low and residence
      time is long, resulting in a high capture probability; although these cells are
      also repelled from the shoulder region, the high local fluid velocity at the
      shoulder minimizes the impact on the overall transport and capture. Likewise,
      cells undergoing negative DEP (nDEP) are repelled from regions of high capture
      probability and attracted to regions where capture is unlikely. These simulations
      predict that DEP can be used to reduce the probability of capturing contaminating
      peripheral blood mononuclear cells (using nDEP) from 0.16 to 0.01 while
      simultaneously increasing the capture of several pancreatic cancer cell lines
      from 0.03-0.10 to 0.14-0.55, laying the groundwork for the experimental study of
      hybrid DEP-immunocapture obstacle array microdevices. 

PMID- 25759750
TI  - Single-cell printing based on impedance detection.
AB  - Label-free isolation of single cells is essential for the growing field of single
      cell analysis. Here, we present a device which prints single living cells
      encapsulated in free-flying picoliter droplets. It combines inkjet printing and
      impedance flow cytometry. Droplet volume can be controlled in the range of 500 pl
      800 pl by piezo actuator displacement. Two sets of parallel facing electrodes in
      a 50 MUm * 55 MUm channel are applied to measure the presence and velocity of a
      single cell in real-time. Polystyrene beads with <5% variation in diameter
      generated signal variations of 12%-17% coefficients of variation. Single bead
      efficiency (i.e., printing events with single beads vs. total number of printing
      events) was 73% +/- 11% at a throughput of approximately 9 events/min. Viability
      of printed HeLa cells and human primary fibroblasts was demonstrated by culturing
      cells for at least eight days. 

PMID- 25759751
TI  - A valve-less microfluidic peristaltic pumping method.
AB  - We demonstrate a valve-less microfluidic peristaltic pumping method which enables
      the delivery of continuous nanoliter-scale flow with high precision. The fluid is
      driven by squeezing the microchannels embedded in a poly(dimethylsiloxane) device
      with rolling cams or bearings. We achieve continuous and uniform flow with
      velocity range from 1 to 500 nl/s, with outflow volume error within 3 nl. The
      devices show enhanced backpressure resistance up to 340 kPa. This method also
      shows great flexibility. By altering the channels' layout, emulsions and plugs
      can be generated easily. These low-cost and easy-to-fabricate micro-pumps offer
      novel approaches for liquid actuation in various microfluidic applications. 

PMID- 25759752
TI  - On demand nanoliter-scale microfluidic droplet generation, injection, and mixing
      using a passive microfluidic device.
AB  - We here present and characterize a programmable nanoliter scale droplet-on-demand
      device that can be used separately or readily integrated into low cost single
      layer rapid prototyping microfluidic systems for a wide range of user
      applications. The passive microfluidic device allows external (off-the-shelf)
      electronically controlled pinch valves to program the delivery of nanoliter scale
      aqueous droplets from up to 9 different inputs to a central outlet channel. The
      inputs can be either continuous aqueous fluid streams or microliter scale aqueous
      plugs embedded in a carrier fluid, in which case the number of effective input
      solutions that can be employed in an experiment is no longer strongly constrained
      (100 s-1000 s). Both nanoliter droplet sequencing output and nanoliter-scale
      droplet mixing are reported with this device. Optimization of the geometry and
      pressure relationships in the device was achieved in several hardware iterations
      with the support of open source microfluidic simulation software and equivalent
      circuit models. The requisite modular control of pressure relationships within
      the device is accomplished using hydrodynamic barriers and matched resistance
      channels with three different channel heights, custom parallel reversible
      microfluidic I/O connections, low dead-volume pinch valves, and a simply
      adjustable array of external screw valves. Programmable sequences of droplet
      mixes or chains of droplets can be achieved with the device at low Hz
      frequencies, limited by device elasticity, and could be further enhanced by valve
      integration. The chip has already found use in the characterization of droplet
      bunching during export and the synthesis of a DNA library. 

PMID- 25759753
TI  - Biomimetics of fetal alveolar flow phenomena using microfluidics.
AB  - At the onset of life in utero, the respiratory system begins as a liquid-filled
      tubular organ and undergoes significant morphological changes during fetal
      development towards establishing a respiratory organ optimized for gas exchange.
      As airspace morphology evolves, respiratory alveolar flows have been hypothesized
      to exhibit evolving flow patterns. In the present study, we have investigated
      flow topologies during increasing phases of embryonic life within an anatomically
      inspired microfluidic device, reproducing real-scale features of fetal airways
      representative of three distinct phases of in utero gestation. Micro-particle
      image velocimetry measurements, supported by computational fluid dynamics
      simulations, reveal distinct respiratory alveolar flow patterns throughout
      different stages of fetal life. While attached, streamlined flows characterize
      the shallow structures of premature alveoli indicative of the onset of saccular
      stage, separated recirculating vortex flows become the signature of developed and
      extruded alveoli characteristic of the advanced stages of fetal development. To
      further mimic physiological aspects of the cellular environment of developing
      airways, our biomimetic devices integrate an alveolar epithelium using the A549
      cell line, recreating a confluent monolayer that produces pulmonary surfactant.
      Overall, our in vitro biomimetic fetal airways model delivers a robust and
      reliable platform combining key features of alveolar morphology, flow patterns,
      and physiological aspects of fetal lungs developing in utero. 

PMID- 25759754
TI  - Distinctive translational and self-rotational motion of lymphoma cells in an
      optically induced non-rotational alternating current electric field.
AB  - In this paper, the translational motion and self-rotational behaviors of the Raji
      cells, a type of B-cell lymphoma cell, in an optically induced, non-rotational,
      electric field have been characterized by utilizing a digitally programmable and
      optically activated microfluidics chip with the assistance of an externally
      applied AC bias potential. The crossover frequency spectrum of the Raji cells was
      studied by observing the different linear translation responses of these cells to
      the positive and negative optically induced dielectrophoresis force generated by
      a projected light pattern. This digitally projected spot served as the virtual
      electrode to generate an axisymmetric and non-uniform electric field. Then, the
      membrane capacitance of the Raji cells could be directly measured. Furthermore,
      Raji cells under this condition also exhibited a self-rotation behavior. The
      repeatable and controlled self-rotation speeds of the Raji cells to the
      externally applied frequency and voltage were systematically investigated and
      characterized via computer-vision algorithms. The self-rotational speed of the
      Raji cells reached a maximum value at 60 kHz and demonstrated a quadratic
      relationship with respect to the applied voltage. Furthermore, optically
      projected patterns of four orthogonal electrodes were also employed as the
      virtual electrodes to manipulate the Raji cells. These results demonstrated that
      Raji cells located at the center of the four electrode pattern could not be self
      rotated. Instead any Raji cells that deviated from this center area would also
      self-rotate. Most importantly, the Raji cells did not exhibit the self-rotational
      behavior after translating and rotating with respect to the center of any two
      adjacent electrodes. The spatial distributions of the electric field generated by
      the optically projected spot and the pattern of four electrodes were also modeled
      using a finite element numerical simulation. These simulations validated that the
      electric field distributions were non-uniform and non-rotational. Hence, the non
      uniform electric field must play a key role in the self-rotation of the Raji
      cells. As a whole, this study elucidates an optoelectric-coupled microfluidics
      based mechanism for cellular translation and self-rotation that can be used to
      extract the dielectric properties of the cells without using conventional metal
      based microelectrodes. This technique may provide a simpler method for label-free
      identification of cancerous cells with many associated clinical applications. 

PMID- 25759755
TI  - Ion concentration polarization on paper-based microfluidic devices and its
      application to preconcentrate dilute sample solutions.
AB  - Microfluidic paper-based analytical devices (MUPADs) are a promising solution for
      a wide range of point-of-care applications. The feasibility of inducing ion
      concentration polarization (ICP) on MUPADs has thus far attracted little
      attention. Accordingly, this study commences by demonstrating the ICP phenomenon
      in a MUPAD with a Nafion ion-selective membrane. We are the first to measure the
      current-voltage curve on a Nafion-coated MUPAD in order to indicate that the ion
      depletion occurs and the ICP is triggered when the current reaches the limiting
      current. The ICP effect is then exploited to preconcentrate fluorescein on MUPADs
      incorporating straight and convergent channels. By an optimal geometric design,
      it is shown that the convergent channel results in a greater preconcentration
      effect than the straight channel. Specifically, a 20-fold enhancement in the
      sample concentration is achieved after 130 s given an initial concentration of
      [Formula: see text] M and an external potential of 50 V. By contrast, the
      straight channel yields only a 10-fold improvement in the concentration after 180
      s. Further, the practical feasibility of the proposed convergent-channel MUPAD is
      demonstrated using fluorescein isothiocyanate labeled bovine serum albumin. The
      experimental results show that a 15-fold enhancement of the initial sample
      concentration ([Formula: see text] M) is obtained after 120 s given an external
      potential of 50 V. 

PMID- 25759756
TI  - An integrated platform enabling optogenetic illumination of Caenorhabditis
      elegans neurons and muscular force measurement in microstructured environments.
AB  - Optogenetics has been recently applied to manipulate the neural circuits of
      Caenorhabditis elegans (C. elegans) to investigate its mechanosensation and
      locomotive behavior, which is a fundamental topic in model biology. In most
      neuron-related research, free C. elegans moves on an open area such as agar
      surface. However, this simple environment is different from the soil, in which C.
      elegans naturally dwells. To bridge up the gap, this paper presents integration
      of optogenetic illumination of C. elegans neural circuits and muscular force
      measurement in a structured microfluidic chip mimicking the C. elegans soil
      habitat. The microfluidic chip is essentially a ~1 * 1 cm(2) elastomeric
      polydimethylsiloxane micro-pillar array, configured in either form of lattice
      (LC) or honeycomb (HC) to mimic the environment in which the worm dwells. The
      integrated system has four key modules for illumination pattern generation,
      pattern projection, automatic tracking of the worm, and force measurement.
      Specifically, two optical pathways co-exist in an inverted microscope, including
      built-in bright-field illumination for worm tracking and pattern generation, and
      added-in optogenetic illumination for pattern projection onto the worm body
      segment. The behavior of a freely moving worm in the chip under optogenetic
      manipulation can be recorded for off-line force measurements. Using wild-type N2
      C. elegans, we demonstrated optical illumination of C. elegans neurons by
      projecting light onto its head/tail segment at 14 Hz refresh frequency. We also
      measured the force and observed three representative locomotion patterns of
      forward movement, reversal, and omega turn for LC and HC configurations. Being
      capable of stimulating or inhibiting worm neurons and simultaneously measuring
      the thrust force, this enabling platform would offer new insights into the
      correlation between neurons and locomotive behaviors of the nematode under a
      complex environment. 

PMID- 25759757
TI  - Surface protein gradients generated in sealed microchannels using spatially
      varying helium microplasma.
AB  - Spatially varied surface treatment of a fluorescently labeled Bovine Serum
      Albumin (BSA) protein, on the walls of a closed (sealed) microchannel is achieved
      via a well-defined gradient in plasma intensity. The microchips comprised a
      microchannel positioned in-between two microelectrodes (embedded in the chip)
      with a variable electrode separation along the length of the channel. The channel
      and electrodes were 50 MUm and 100 MUm wide, respectively, 50 MUm deep, and
      adjacent to the channel for a length of 18 mm. The electrode separation distance
      was varied linearly from 50 MUm at one end of the channel to a maximum distance
      of 150, 300, 500, or 1000 MUm to generate a gradient in helium plasma intensity.
      Plasma ignition was achieved at a helium flow rate of 2.5 ml/min, 8.5 kVpk-pk,
      and 10 kHz. It is shown that the plasma intensity decreases with increasing
      electrode separation and is directly related to the residual amount of BSA left
      after the treatment. The plasma intensity and surface protein gradient, for the
      different electrode gradients studied, collapse onto master curves when plotted
      against electrode separation. This precise spatial control is expected to enable
      the surface protein gradient to be tuned for a range of applications, including
      high-throughput screening and cell-biomolecule-biomaterial interactions. 

PMID- 25759758
TI  - Recovery from alopecia areata in a patient with autoimmune polyglandular syndrome
      type 3.
AB  - Recovery from alopecia is rare in autoimmune polyglandular syndrome (APS). A 41
      year-old male was admitted to our hospital with hyperglycemia. He developed
      alopecia areata (AA) 5 months before admission and developed thirst, polyuria,
      and anorexia in 2 weeks. His plasma glucose level upon admission was 912 mg/dl
      (50.63 mmol/l) and HbA1c was 13.7%. Although urinary and plasma C-peptide levels
      showed that insulin secretion was not depleted, anti-insulinoma-associated
      antigen 2 antibody was present. In addition, measurement of thyroid
      autoantibodies revealed the presence of Hashimoto's thyroiditis. These findings
      suggested a diagnosis of APS type 3. The patient has showed signs of improvement
      with the continuation of insulin therapy. During the successful control of
      diabetes, he had total hair regrowth within 2-3 months. Human leukocyte antigen
      typing showed that DRB1*1501-DQB1*0602 and DQB1*0301 were present. Similar cases
      should be accumulated to clarify the association of APS type 3 with recovery from
      AA. LEARNING POINTS: Alopecia in diabetic patients is a suspicious manifestation
      of autoimmune type 1 diabetes.Patients with autoimmune type 1 diabetes
      specifically manifesting alopecia should be further examined for diagnosis of
      APS.Insulin-mediated metabolic improvement may be a factor, but not the sole
      factor, determining a favorable outcome of alopecia in patients with autoimmune
      type 1 diabetes.

PMID- 25759759
TI  - Xanthogranulomatous hypophysitis: a rare and often mistaken pituitary lesion.
AB  - Xanthogranulomatous hypophysitis (XGH) is a very rare form of pituitary
      hypophysitis that may present both clinically and radiologically as a neoplastic
      lesion. It may either be primary with an autoimmune aetiology and can occur in
      isolation or as a part of autoimmune systemic disease or secondary as a reactive
      degenerative response to an epithelial lesion (e.g. craniopharyngioma (CP),
      Rathke's cleft cyst, germinoma and pituitary adenomas) or as a part of a
      multiorgan systemic involvement such as tuberculosis, sarcoidosis or
      granulomatosis. It may also present with a variation of symptoms in children and
      adults. Our case series compares the paediatric and adult presentations of XGH
      and the differential diagnoses considered in one child and two adult patients,
      highlighting the wide spectrum of this condition. Endocrine investigations
      suggested panhypopituitarism in all three patients and imaging revealed a
      suprasellar mass compressing the optic chiasm suggestive of CP or Rathke's cleft
      cyst in one patient and non-functioning pituitary macroadenoma in two patients.
      Magnetic resonance imaging (MRI) demonstrated mixed signal intensities on T1- and
      T2-weighted sequences. Following endoscopic transsphenoidal surgery, histological
      analysis revealed necrotic material with a xanthogranulomatous reaction
      confirming XGH in two patients and a necrobiotic granulomatous chronic
      inflammatory infiltrate with neutrophils in one patient, which is not typical of
      current descriptions of this disorder. This case series describes the wide
      spectrum of XGH disease that is yet to be defined. Mixed signal intensities on T1
      and T2-weighted MRI sequences may indicate XGH and diagnosis is confirmed by
      histology. Histological variation may indicate an underlying systemic process.
      LEARNING POINTS: XGH is a rare form of pituitary hypophysitis with a wide
      clinical and histological spectrum and can mimic a neoplastic lesion.XGH
      primarily presents with growth arrest in children and pubertal arrest in
      adolescents. In adults, the presentation may vary.A combination of
      hypopituitarism and mixed signal intensity lesion on MRI is suggestive of XGH and
      should be considered in the differential diagnosis of sellar lesions.Radical
      surgery is the treatment of choice and carries an excellent prognosis with no
      recurrence.

PMID- 25759760
TI  - A novel melanoma therapy stirs up a storm: ipilimumab-induced thyrotoxicosis.
AB  - Ipilimumab, a novel therapy for metastatic melanoma, inhibits cytotoxic T
      lymphocyte apoptosis, causing both antitumor activity and significant
      autoimmunity, including autoimmune thyroiditis. Steroids are frequently used in
      treatment of immune-related adverse events; however, a concern regarding the
      property of steroids to reduce therapeutic antitumor response exists. This study
      describes the first reported case of ipilimumab-associated thyroid storm and
      implicates iopanoic acid as an alternative therapy for immune-mediated adverse
      effects. An 88-year-old woman with metastatic melanoma presented with fatigue,
      anorexia, decreased functional status, and intermittent diarrhea for several
      months, shortly after initiation of ipilimumab - a recombinant human monoclonal
      antibody to the cytotoxic T-lymphocyte-associated antigen 4 (CTLA4). On arrival,
      she was febrile, tachycardic, and hypertensive with a wide pulse pressure, yet
      non-toxic appearing. She had diffuse, non-tender thyromegaly. An
      electrocardiogram (EKG) revealed supraventricular tachycardia. Blood, urine, and
      stool cultures were collected, and empiric antibiotics were started. A computed
      tomography (CT) angiogram of the chest was negative for pulmonary embolism or
      pneumonia, but confirmed a diffusely enlarged thyroid gland, which prompted
      thyroid function testing. TSH was decreased at 0.16 MUIU/ml (normal 0.3-4.7);
      free tri-iodothyronine (T3) was markedly elevated at 1031 pg/dl (normal 249-405),
      as was free thyroxine (T4) at 5.6 ng/dl (normal 0.8-1.6). With iopanoic acid and
      methimazole therapy, she markedly improved within 48 h, which could be attributed
      to lowering of serum T3 with iopanoic acid rather than to any effect of the
      methimazole. Ipilimumab is a cause of overt thyrotoxicosis and its immune
      mediated adverse effects can be treated with iopanoic acid, a potent inhibitor of
      T4-to-T3 conversion. LEARNING POINTS: While ipilimumab more commonly causes
      autoimmune thyroiditis, it can also cause thyroid storm and clinicians should
      include thyroid storm in their differential diagnosis for patients who present
      with systemic inflammatory response syndrome.Immune-related adverse reactions
      usually occur after 1-3 months of ipilimumab and baseline thyroid function
      testing should be completed before initiation with ipilimumab.Conflicting data
      exist on the use of prednisone for treatment of CTLA4 adverse effects and its
      attenuation of ipilimumab's antitumor effect. Iopanoic acid may be considered as
      an alternative therapy in this setting.

PMID- 25759761
TI  - Antibodies to infliximab and adalimumab in patients with rheumatoid arthritis in
      clinical remission: a cross-sectional study.
AB  - Objective. To investigate if antibodies towards biological TNF-alpha inhibitors
      (anti-TNFi Abs) are present in patients with rheumatoid arthritis (RA) in
      clinical remission and to relate any anti-TNFi Abs to circulating level of TNF
      alpha inhibitor (TNFi). Methods. Patients with RA, treated with infliximab or
      adalimumab, and in clinical remission (DAS28(CRP) < 2.6) were included from 6 out
      patient clinics. In blood samples, presence of anti-TNFi Abs was determined by
      radioimmunoassay, and concentration of bioactive TNFi was measured by a cell
      based reporter gene assay. Results. Anti-TNFi Abs were present in 8/44 patients
      (18%) treated with infliximab and 1/49 patients (2%) treated with adalimumab (p =
      0.012). In the former group, anti-TNFi Abs corresponded with low levels of TNFi
      (p = 0.048). Anti-TNFi Ab-positive patients had shorter disease duration at
      initiation of TNFi therapy (p = 0.023) but were similar for the rest of the
      compared parameters. Conclusions. In RA patients in clinical remission, anti-TNFi
      Abs occur frequently in patients treated with infliximab, while they occur rarely
      in patients treated with adalimumab. Presence of anti-infliximab Abs is
      accompanied by low or undetectable levels of infliximab. These data suggest that
      continued infliximab treatment may be redundant in a proportion of RA patients
      treated with infliximab and in clinical remission. 

PMID- 25759763
TI  - A Rare and Unexpected Side-Effect of Cannabis Use: Abdominal Pain due to Acute
      Pancreatitis.
AB  - Acute pancreatitis is a frequently encountered disorder in patients presenting to
      emergency units. Biliary system disorders, alcohol consumption, infections, and
      drugs are among the causes of acute pancreatitis. However, it is sometimes
      difficult to determine the etiology of this disorder, particularly if the patient
      does not wish to disclose his consumption of cannabis, the use of which is
      illegal. 

PMID- 25759762
TI  - Effects of physical exercise on individual resting state EEG alpha peak
      frequency.
AB  - Previous research has shown that both acute and chronic physical exercises can
      induce positive effects on brain function and this is associated with
      improvements in cognitive performance. However, the neurophysiological mechanisms
      underlying the beneficial effects of exercise on cognitive processing are not
      well understood. This study examined the effects of an acute bout of physical
      exercise as well as four weeks of exercise training on the individual resting
      state electroencephalographic (EEG) alpha peak frequency (iAPF), a
      neurophysiological marker of the individual's state of arousal and attention, in
      healthy young adults. The subjects completed a steady state exercise (SSE)
      protocol or an exhaustive exercise (EE) protocol, respectively, on two separate
      days. EEG activity was recorded for 2 min before exercise, immediately after
      exercise, and after 10 min of rest. All assessments were repeated following four
      weeks of exercise training to investigate whether an improvement in physical
      fitness modulates the resting state iAPF and/or the iAPF response to an acute
      bout of SSE and EE. The iAPF was significantly increased following EE (P = 0.012)
      but not following SSE. It is concluded that the iAPF is increased following
      intense exercise, indicating a higher level of arousal and preparedness for
      external input.

PMID- 25759764
TI  - Association of bone loss with the upregulation of survival-related genes and
      concomitant downregulation of Mammalian target of rapamycin and osteoblast
      differentiation-related genes in the peripheral blood of late postmenopausal
      osteoporotic women.
AB  - We aimed to identify bone related markers in the peripheral blood of osteoporotic
      (OP) patients that pointed toward molecular mechanisms underlying late
      postmenopausal bone loss. Whole blood from 22 late postmenopausal OP patients and
      26 healthy subjects was examined. Bone mineral density (BMD) was measured by DXA.
      Protein levels of p70-S6K, p21, MMP-9, TGFbeta1, and caspase-3 were quantified by
      ELISA. Gene expression was measured using real-time RT-PCR. OP registered by low
      BMD indices in late postmenopausal patients was associated with a significant
      upregulation of autophagy protein ULK1, cyclin-dependent kinase inhibitor p21,
      and metalloproteinase MMP-9 gene expression in the blood compared to the healthy
      controls and in a significant downregulation of mTOR (mammalian target of
      rapamycin), RUNX2, and ALPL gene expression, while expression of cathepsin K,
      caspase-3, transforming growth factor (TGF) beta1, interleukin- (IL-) 1beta, and
      tumor necrosis factor alpha (TNFalpha) was not significantly affected. We also
      observed a positive correlation between TGFbeta1 and RUNX2 expression and BMD at
      femoral sites in these patients. Therefore, bone loss in late postmenopausal OP
      patients is associated with a significant upregulation of survival-related genes
      (ULK1 and p21) and MMP-9, as well as the downregulation of mTOR and osteoblast
      differentiation-related genes (RUNX2 and ALPL) in the peripheral blood compared
      to the healthy controls. 

PMID- 25759765
TI  - Neoadjuvant radiotherapy/chemoradiotherapy in locally advanced non-small cell
      lung cancer.
AB  - Locally advanced non-small cell lung cancer (NSCLC) consists of a heterogeneous
      group of patients, and the optimal treatment is still controversial. The current
      standard of care is concurrent chemoradiotherapy. The prognosis is still poor,
      with high rates of local and distant failure despite multimodality treatment. One
      of the efforts to improve outcomes in these patients is to use neoadjuvant
      treatment to improve resectability, and downstaging the nodal disease, which has
      a clear impact on prognosis. Radiotherapy as the sole neoadjuvant modality has
      been used historically without any survival benefit, but with increased toxicity.
      After the demonstrating a survival benefit by combining radiotherapy and
      chemotherapy, phase II studies were started to determine the neoadjuvant
      administration of these two modalities together. Although the results of these
      studies revealed a heterogeneous postinduction pathologic complete response,
      tumor and nodal down-staging can be achieved at the cost of a slightly higher
      morbidity and mortality. Subsequent phase III trials also failed to show a
      survival benefit to surgery, but indicated that there may be a subset of patients
      with locally advanced disease who can benefit from resection unless pneumonectomy
      is not provided. In order to increase the efficacy of radiotherapy,
      hyperfractionated-accelerated schedules have been used with promising complete
      pathologic response rates, which might improve prognosis. Recently, studies
      applying high radiotherapy doses in the neoadjuvant setting demonstrated the
      safety of resection after radiotherapy, with high nodal clearance rates and
      encouraging long-term survival results. In conclusion, neoadjuvant treatment of
      locally advanced NSCLC is one of the most challenging issues in the treatment of
      this disease, but it can be offered to appropriately selected patients, and
      should be done by a multidisciplinary team. Individual risk profiles, definite
      role of radiotherapy with optimal timing, and dose need to be clarified by
      carefully designed clinical trials. 

PMID- 25759766
TI  - Treatment of early stage non-small cell lung cancer: surgery or stereotactic
      ablative radiotherapy?
AB  - The management of early-stage Non-small Cell Lung Cancer (NSCLC) has improved
      recently due to advances in surgical and radiation modalities. Minimally-invasive
      procedures like Video-assisted thoracoscopic surgery (VATS) lobectomy decreases
      the morbidity of surgery, while the numerous methods of staging the mediastinum
      such as endobronchial and endoscopic ultrasound-guided biopsies are helping to
      achieve the objectives much more effectively. Stereotactic Ablative Radiotherapy
      (SABR) has become the frontrunner as the standard of care in medically inoperable
      early stage NSCLC patients, and has also been branded as tolerable and highly
      effective. Ongoing researches using SABR are continuously validating the optimal
      dosing and fractionation schemes, while at the same time instituting its role for
      both inoperable and operable patients. 

PMID- 25759767
TI  - For what reasons do patients file a complaint? A retrospective study on patient
      rights units' registries.
AB  - BACKGROUND: In 2004, Patient Rights Units were established in all public
      hospitals in Turkey to allow patients to voice their complaints about services.
      AIMS: To determine what violations are reflected into the complaint mechanism,
      the pattern over time, and patients' expectations of the services. STUDY DESIGN:
      Descriptive study. METHODS: A retrospective study performed using the complaint
      database of the Istanbul Health Directorate, from 2005 to 2011. RESULTS: The
      results indicate that people who are older than 40 years, women, and those with
      less than high school education are the most common patients in these units. A
      total of 218,186 complaints were filed. Each year, the number of complaints
      increased compared to the previous year, and nearly half of the applications were
      made in 2010 and 2011 (48.9%). The three most frequent complaints were "not
      benefiting from services in general" (35.4%), "not being treated in a respectable
      manner and in comfortable conditions" (17.8%), and "not being properly informed"
      (13.5%). Two-thirds of the overall applications were found in favour of the
      patients (63.3%), and but this rate has decreased over the years. CONCLUSION:
      Patients would like to be treated in a manner that respects their human dignity.
      Educating healthcare workers on communication skills might be a useful
      initiative. More importantly, health policies and the organisation of services
      should prioritise patient rights. It is only then would be possible to exercise
      patient rights in reality.

PMID- 25759768
TI  - Evaluation on shear bond strength of different glass ionomer and hydroxy apatite
      cements used in ossiculoplasty.
AB  - BACKGROUND: Glass ionomer cements (GIC) have been widely used in dentistry for
      many years. In recent years, GIC have also been used for ossiculoplasty. The bond
      strength of GIC used in ossiculoplasty and the way they may change over the years
      in the cementation area are being questioned. The bonding strength of the
      substance may be of importance for long-term outcomes. AIMS: The aim of this
      study was to investigate the bond strength of different GIC on ossicles. STUDY
      DESIGN: In vitro study. METHODS: Twenty ossicles were obtained from patients who
      had undergone ear surgery. All specimens were randomly divided into four
      subgroups. All specimens were inserted into a specially designed apparatus for
      shear bond strength (SBS) testing. The tested materials [Aqua Meron (AM), Aqua
      Cem (AC), Ketac Cem (KC), and Otomimix CPB (OH)] were prepared and applied
      according to the manufacturer's instructions. The SBS was tested using a
      universal testing machine at a crosshead speed of 0.5 mm/min. RESULTS: The mean
      SBSs were found to be 13.28 MPa, 23.43 MPa, 8.51MPa, and 1.78 MPa for AM, AC, KC,
      and OH, respectively. AC had the highest SBS, which was statistically
      significantly different from that of KC and OH (p<0.05). Both AM and KC had
      higher SBS than OH (p<0.05). CONCLUSION: The results obtained in this study by
      investigating the bone-bonding strength of cements widely used in ossiculoplasty
      demonstrate that some of these substances have a greater ability to bond to
      ossicles compared to others. Further clinical investigations are needed to test
      different parameters.

PMID- 25759769
TI  - Imp3 expression in benign and malignant thyroid tumors and hyperplastic nodules.
AB  - BACKGROUND: IMP3, a member of insulin-like growth factor II m RNA binding protein
      family, seems to be promising in the diagnosis of carcinomas of many organs as
      well as malignant melanomas and some sarcomas. It is postulated that it might be
      a marker of malignancy. The results of the few prior studies indicate that IMP3
      has the potential to be useful in distinguishing benign and malignant tumors of
      thyroid. AIMS: We aimed to evaluate the immunohistochemical expression of IMP3 in
      non-neoplastic nodules and benign and malignant tumors of the thyroid. STUDY
      DESIGN: Diagnostic accuracy study. METHODS: Overall, 92 thyroid lesions,
      including 22 nodular hyperplasia (NH), 14 follicular adenoma (FA), 9 follicular
      carcinoma (FC), 37 papillary carcinoma (PC) (15 follicular variant), 3 well
      differentiated carcinoma-not otherwise specified (WDC-NOS), 4 poorly
      differentiated carcinoma (PDC) and anaplastic carcinoma (AC) were included.
      Immunohistochemically, cytoplasmic expression of IMP3 was evaluated in terms of
      extent and intensity of the staining semi-quantitatively and an
      immunohistochemical score (IHS) was obtained for each case. A score higher than 2
      was considered positive staining. RESULTS: In contrast with previous studies, we
      observed positive staining in benign lesions, especially in benign tumors. For
      identifying malignant tumors, the sensitivity of IMP3 was 82.1%, specificity was
      33.3%, positive predictive value (PPV) was 65.7% and negative predictive value
      (NPV) was 54.5%. In distinguishing neoplastic and hyperplastic lesions, the
      sensitivity was 50%, specificity was 15.7%, PPV was 15.7% and NPV was 50%. The
      IMP3 expression was similar for FA and well differentiated carcinomas (p=0.434),
      but there was a significant difference between hyperplastic nodules and FA
      (p=0.011). CONCLUSION: Our data suggest that IMP3 is effective in discriminating
      hyperplastic and neoplastic lesions but not useful in differentiating benign
      tumors from malignant tumors.

PMID- 25759770
TI  - Outcomes after transhiatal esophagectomies in an eastern-European low-volume
      center.
AB  - BACKGROUND: The present study proposes to analyze the results obtained after
      transhiatal esophagectomies (THE), from the perspective of an Eastern European
      surgical center with low esophageal resection volume (LV). AIMS: Our analysis,
      which to the authors' knowledge is the first of its kind in Romania, has the
      purpose of comparing our results with those obtained in higher or similar volume
      centers, in order to derive conclusions regarding the quality of therapeutic
      management for patients diagnosed with esophageal cancer in Romania. STUDY
      DESIGN: Retrospective observational study. METHODS: In total, 70 patients were
      included, in whom THE was performed during the period 1997-2013 by six senior
      surgeons. The majority of our patients had esophageal cancers (n=66; 94.3%); we
      also performed 4 THE procedures for benign conditions (n=3; 4.27%) and esophageal
      perforation (n=1; 1.42%). RESULTS: The majority of cancer-group patients had
      T3/N+ tumors. The nodal involvement in the T2, T3 and T4 categories was 9.9%,
      21.6% and 35.1%, respectively. Complications were identified in 45 patients
      (68.2%), with the majority being represented by pulmonary complications (16
      patients; 24.3%) and cervical leaks (15 cases; 22.7%). In-hospital mortality was
      9.09%. We found a one-year overall survival rate of 58.7% (95%CI: 51.7-65.7%),
      27.2% at 2 years (95%CI: 21.2-36.2%) and 10.5% at 3 years (95%CI: 6.5-14.5%). The
      median survival rate was estimated to be 16 months. CONCLUSION: Morbidity and in
      hospital mortality after THE was performed in low-volume centers, despite being
      significantly higher than reported in HV centers, could be kept at reasonable
      rates. In our opinion, the measures which have the potential to raise the
      standard of care for patients diagnosed with esophageal cancer in Romania are
      represented by the standardization of therapeutic and diagnostic protocols for
      esophageal cancer and the centralization of these major oncologic interventions
      in surgical excellence centers.

PMID- 25759771
TI  - Immunoserologic pepsin detection in the saliva as a non-invasive rapid diagnostic
      test for laryngopharyngeal reflux.
AB  - BACKGROUND: The most common tool for the diagnosis of laryngopharyngeal reflux
      (LPR) is still 24-hours esophageal pH monitoring; there is lack of non-invasive,
      less expensive and accurate diagnostic tools for this frequent disease. AIMS: To
      evaluate the accuracy of immunoserologic pepsin detection in the saliva for the
      diagnosis of LPR. STUDY DESIGN: Cross-sectional study. METHODS: A two channeled
      24-hour esophageal pH monitoring catheter was placed in patients with a suspicion
      of LPR. During the 24-hour period, each patient gave one sample of sputum for the
      immunoserologic pepsin detection test. Pathologic gastroesophageal reflux (GER)
      findings, LPR findings, pH score in the proximal and distal probes when the
      sputum sample was given were recorded. The sensitivity, specificity, positive and
      negative predictive values of the pepsin detection test were analyzed and
      compared to pH monitoring scores. RESULTS: The study group consisted of 20
      patients who met the criteria. A positive pepsin detection test was elicited from
      6 patients. The sensitivity and specificity of the pepsin detection test was 33%
      and 100%, respectively. A positive predictive value of 100% was recorded. When
      the pH results of the pepsin positive patients (PPP) and the rest of the study
      group in the proximal probe at the sample time were compared, the PPP had an
      apparent acidic pH value compared to the pepsin negative patients (pH: 3.26 for
      the PPP, pH: 6.81 for the pepsin negative patients). CONCLUSION: Pepsin detection
      in the saliva is a recent method and becoming increasingly popular. Because of
      the benefits and ease of application, a positive salivary pepsin test in a
      patient suspected of having LPR can be a cost effective, accurate and alternative
      diagnostic method. Increasing the daily number of sputum samples may increase the
      sensitivity of the test.

PMID- 25759772
TI  - Spot protein/creatinine ratio in preeclampsia as an alternative for 24-hour urine
      protein.
AB  - BACKGROUND: Proteinuria is a major component of preeclampsia. Urine protein
      measurement after 24-hour urine collection is the traditional standard method for
      the detection of proteinuria. It is time-consuming. As an alternative, random
      spot sampling for a urine protein to creatinine (P/C) ratio has been
      investigated. AIMS: The aim of the study was to determine the diagnostic accuracy
      of the protein to creatinine ratio (P/C) compared with 24-hour urine collection
      for the detection of remarkable proteinuria and to evaluate the P/C ratio for
      different proteinuria ranges in patients with preeclampsia. STUDY DESIGN: Case
      control study. METHODS: Two hundred and eleven pregnant women who met the
      criteria of preeclampsia comprised the study group and fifty three pregnant women
      were taken as the control group. Spot urine specimens for measuring P/C ratio
      were obtained taken immediately before 24-hour urine collection. The correlation
      between the P/C ratio in the spot urine samples and urinary protein excretion in
      the 24-hour collections was examined using the Spearman correlation test.
      RESULTS: It was found a good positive correlation between the P/C ratio and 24
      hour protein excretion, with a correlation coefficient (r) of 0.758. The best cut
      off which gave the maximum area under the curve was 0.45 for 300 mg, 0.9 for 1000
      mg, 1.16 for 2000 mg, 1.49 for 3000 mg, 2.28 for 4000 mg and 2.63 for 5000 mg per
      24h. A P/C ratio above 0.9 strongly predicts significant proteinuria for more
      than 1 gram (AUC 0.97, 95% CI: 0.94-0.99 and sensitivity, specificity, positive
      and negative predictive value of 91%, 95.4%, 95.2%, and 91.2%, respectively).
      CONCLUSION: The P/C ratio can be used as a screening test as a good predictor for
      remarkable proteinuria. The P/C ratio seems to be highly predictive for diagnosis
      to detect proteinuria over one gram and it could be used as a rapid alternative
      test in preeclamptic patients not to delay implementation treatment.

PMID- 25759773
TI  - Effect of obesity on left ventricular longitudinal myocardial strain by speckle
      tracking echocardiography in children and adolescents.
AB  - BACKGROUND: Impaired subclinical ventricular function may contribute to the risk
      of cardiovascular disease in obesity. AIMS: The aim of this study was to
      determine the influence of obesity on left ventricular (LV) longitudinal
      myocardial function in normotensive obese children using two-dimensional (2D)
      speckle tracking echocardiography (STE). STUDY DESIGN: Case-control study.
      METHODS: Sixty normotensive obese children aged 10-16 years (mean age, 13.9+/-2.3
      years) were compared with 50 normal-weight controls. Obese participants had a
      body mass index (BMI)>=95(th) percentile. Regional strain/strain rate (SR) values
      were compared with left ventricular (LV) parameters. The correlation was studied
      by linear regression analysis. RESULTS: Obese subjects exhibited a significantly
      higher LV end-diastolic diameter, left atrium/aortic diameter ratio, and LV
      mass/index when compared to controls (p<0.001). Left ventricular ejection
      fraction and regional systolic myocardial velocities were similar in the obese
      and control groups. By 2D STE, regional strain of both the septal wall (average
      strain: -16.0+/-3.9% vs -21.9+/-2.4%, p<0.001) and lateral wall (average strain: 
      15.6+/-2.3% vs -22.9+/-3.5%, p<0.001); regional SR of both the septal wall
      (average SRsys: -0.7+/-0.22 s(-1) vs -1.3+/-0.32 s(-1), p<0.001) and lateral wall
      (average SRsys: -0.67+/-0.19 s(-1) vs -1.33+/-0.31 s(-1), p<0.001); regional
      SRE/A of both the septal wall (average SRE/A: 1.8+/-0.83 vs. 2.2+/-0.91, p:
      0.004) and lateral wall (average SRE/A: 1.4+/-0.43 vs. 2.4+/-1.21, p<0.001); and
      global strain (-14.6+/-7.34% vs -20.9+/-3.24%, p<0.001) were lower in the obese
      group compared with the controls. These strain imaging parameters appear to be
      related to the severity of obesity and can contribute to increased BMI. Left
      ventricular mass was found to be correlated with a decrease in global LV strain.
      CONCLUSION: Our study showed that childhood obesity is associated with an
      alteration in the longitudinal LV function. Segmental analysis of the LV can
      provide subtle markers for the emergence of future obesity-related cardiac
      disease.

PMID- 25759774
TI  - Evaluation of pneumatization in the articular eminence and roof of the glenoid
      fossa with cone-beam computed tomography.
AB  - BACKGROUND: Detection of air cavities, so called pneumatizations, nearby to the
      temporomandibular joint (TMJ) area is important, as they represent sites of
      minimal resistance and facilitate the spread of various pathologies into the
      joint as inflammation, tumor or fractures and serve as a possible complicating
      factor in TMJ surgery. AIMS: To determine the prevalence of pneumatization of the
      articular eminence (PAT) and roof of the glenoid fossa (PRGF) using cone-beam
      computed tomography (CBCT). STUDY DESIGN: Cross-sectional study. METHODS:
      Acquired images of 111 patients (222 TMJs) were evaluated. The presence of
      pneumatization was recorded at the articular eminence and roof of the glenoid
      fossa. Age and gender were recorded for all patients and type (unilocular or
      multilocular) and laterality were noted for the cases of pneumatization. RESULTS:
      The mean age of the study group was 48.86+/-18.31 years. Among all the patients,
      73 (65.8%) had PAT, while 13 (11.7%) had PRGF. Forty-two (37.8%) of the patients
      had PAT bilaterally; whereas 3 of them (2.7%) presented PRGF bilaterally. The
      percentage of PAT was higher for females (73.6%) than males (51.3%) (p<0.05).
      CONCLUSION: CBCT images are an accurate and reliable means of detection of the
      exact size and type of pneumatization and the relationship of pneumatization to
      the adjacent tissues. This is especially significant before a surgical
      intervention is planned in this region, in order to make a sound diagnosis.

PMID- 25759775
TI  - Differences between Solution and Membrane Forms of Chitosan on the In Vitro
      Activity of Fibroblasts.
AB  - BACKGROUND: Chitosan, a linear polysaccharide, has been recently used in
      biomedical applications. In vitro studies have demonstrated its effect on
      cellular growth and its stimulatory action on cellular layer formation. AIMS: The
      present study aims to compare the proliferative effects of chitosan in two forms,
      membranous and solution forms, on Swiss 3T3 mouse embryonic fibroblasts. STUDY
      DESIGN: In vitro study. METHODS: Three experimental groups were formed: cells
      were cultured in a normal medium without chitosan (Control Group); cells were
      cultured either in a medium containing 2.0% chitosan in membranous form (Membrane
      Group) or chitosan solution at a concentration of 2.0% (Solution Group). Two
      different methods were used in the experiments: cells cultured on the medium
      containing chitosan in solution or membranous forms (method 1); and chitosan
      solution or membranous forms were added into the medium containing previously
      cultured cells (method 2). RESULTS: Scanning electron microscopic investigations
      of the experimental groups revealed cells with well-defined cellular projections,
      intact cellular membranes and tight intercellular junctions. They were especially
      prominent in the membrane group of method 1 and in the membrane and solution
      groups of method 2. Mouse monoclonal anti-collagen 1 primary antibody was used to
      indicate collagen synthesis. Prominent collagen synthesis was detected in the
      membrane groups on the 10(th) day of culture for both methods. Bromodeoxyuridine
      (BrdU) and MTT assays were performed in order to assess cellular proliferation
      and viability, respectively. BrdU labelling tests indicated a higher
      proliferation index in the membrane group of method 1 on the 5(th) and 10(th)
      days. For the second method, the membranous form on the 10(th) day and solution
      form on the 5(th) day were the most effective groups in terms of cellular
      proliferation. MTT results reflected a high cellular viability in method 1 on the
      5(th) day of treatment with the membranous form, whereas cellular viability was
      highest in the solution form of method 2 on the 5(th) day. CONCLUSION: The
      membranous form of chitosan induced a significant proliferative effect and
      increased the ratio of cell-to-cell junctions of Swiss 3T3 mouse embryonic
      fibroblasts. Conveniently, the solution form also resulted in enhanced cell
      proliferation and viability compared to the control group. As the solution form
      is easy to prepare and apply to cells compared to the membrane form, the
      application of Chitosan directly to media appears to be a convenient alternative
      for tissue engineering approaches.

PMID- 25759776
TI  - Investigation of Metallo Beta Lactamases and Oxacilinases in Carbapenem Resistant
      Acinetobacter baumannii Strains Isolated from Inpatients.
AB  - BACKGROUND: Resistance to beta-lactam antibiotics is widespread among
      Acinetobacter strains. Plasmid-mediated metallo beta lactamases (MBL) are
      responsible for carbapenem resistance, as are oxacillinases (OXA). In recent
      years, MBL producing carbapenem-resistant strains have been reported in the world
      and in Turkey in increasing rates. In our country, besides the OXA 51-like enzyme
      which is inherent in A. baumannii strains, OXA 58-like and OXA 23-like
      carbapenemases producing strains have also been widely detected. In addition,
      Verona Imipenemase (VIM) and (IMP)-type MBL have been reported in some centers.
      AIMS: The aim of our study was to investigate the presence of carbapenemases in
      Acinetobacter strains isolated from hospitalized patients in Edirne. STUDY
      DESIGN: Cross-sectional study. METHODS: A total of 52 imipenem-resistant A.
      baumannii strains isolated between January and March 2013 were investigated. The
      presence of MBL was described phenotypically by the combined disk diffusion test
      (CDDT), double disk synergy test (DDST), MBL E-test (only performed in 28
      strains) and modified Hodge test. blaIMP, blaVIM, blaGIM, blaSIM, blaSPM genes
      and blaOXA-23, blaOXA-51, blaOXA-40, blaOXA-58 genes were investigated by
      multiplex polymerase chain reaction (PCR). The blaNDM-1 gene was determined by
      PCR. RESULTS: By modified Hodge test, 50 strains (96%) were found to be MBL
      positive. Positivity of MBL was 21% by both CDDT (0.1 M EDTA) and DDST. Twenty
      four of 28 strains (85.7%) were positive by MBL E-test. OXA 23-like and OXA 51
      like carbapenemases were detected in all strains, but OXA 58-like and OXA 40-like
      carbapenemases-producing A. baumannii were not detected. Also, MBL genes were not
      detected by genotypic methods. CONCLUSION: Only OXA 23-like carbapenemase was
      responsible for carbapenem resistance in carbapenem-resistant Acinetobacter
      strains in Edirne. The MBL-producing Acinetobacter strain is not yet a problem in
      our hospital. MBL resistance was found by phenotyping tests, which must be
      confirmed by genotypic methods; multiplex PCR tests can be easily used for
      screening MBL.

PMID- 25759777
TI  - Phenotypes and genotypes of macrolide-resistant streptococcus pneumoniae.
AB  - BACKGROUND: Macrolide resistance in Streptococcus pneumoniae (S. pneumoniae) is a
      worldwide problem. AIMS: The aim of this work was to analyze the phenotypes,
      genotypes, and clonal relatedness among macrolide-resistant S. pneumoniae strains
      isolated from various clinical specimens in our hospital. STUDY DESIGN: Cross
      sectional study. METHODS: 80 non-duplicate S. pneumoniae strains were analyzed by
      polymerase chain reaction for both the erm (B) and mef (A) genes. RESULTS:
      Macrolide resistance was observed in 22.5% (18 strains) of strains. Two (11.2%)
      isolates possessed mef (A), eight possessed erm (B) (44.4%) and eight strains
      (44.4%) were positive for both erm (B) and mef (A) genes. Although BOX-PCR of 18
      macrolide-resistant strains revealed 11 band patterns, they clustered as seven
      clones with a genetic distance >10% to each other. Eight isolates possessed both
      erm (B) and mef (A) genes and belonged to a single clone (44.44% of all macrolide
      resistant strains). CONCLUSION: Increased positivity rates for both resistance
      genes have also been reported from other hospitals in Turkey, but this is the
      first study from Turkey showing the clonal dissemination of both resistance
      genes.

PMID- 25759778
TI  - Effect of rosuvastatin on arginase enzyme activity and polyamine production in
      experimental breast cancer.
AB  - BACKGROUND: Breast cancer is the most common malignant tumour of women around the
      world. As a key enzyme of the urea cycle, arginase leads to the formation of urea
      and ornithine from L-arginine. In the patients with several different cancers,
      arginase has been found to be higher and reported to be a useful biological
      marker. AIMS: The aim of this study was to investigate the effect of rosuvastatin
      on serum and cancer tissue arginase enzyme activity, and ornithine and polyamine
      (putrescine, spermidine, spermine) levels. STUDY DESIGN: Animal experiment.
      METHODS: In this study, 50 male Balb/c mice were used. Erchlich acid tumour cells
      were injected into the subcutaneous part of their left foot. The mice were
      divided into five groups: healthy control group, healthy treatment, tumour
      control, treatment 1 and treatment 2. Then, 1 mg/kg and 20 mg/kg doses of
      rosuvastatin were given intraperitoneally. Serum and tissue arginase enzyme
      activities and tissue ornithine levels were determined spectrophotometrically.
      HPLC measurement of polyamines were applied. RESULTS: Increased serum arginase
      activity and polyamine levels were significantly decreased with rosuvastatin
      treatment. In the tumour tissue, arginase activity and ornithine levels were
      significantly decreased in treatment groups compared to the tumour group. Tissue
      polyamine levels also decreased with rosuvastatin treatment. CONCLUSION: We
      suggest that rosuvastatin may have some protective effects on breast cancer
      development as it inhibits arginase enzyme activity and ornithine levels,
      precursors of polyamines, and also polyamine levels. This protective effect may
      be through the induction of nitric oxide (NO) production via nitric oxide
      synthase (NOS). As a promising anticancer agent, the net effects of rosuvastatin
      in this mechanism should be supported with more advanced studies and new
      parameters.

PMID- 25759779
TI  - The effects of ankaferd blood stopper on the recovery process in an experimental
      oesophageal perforation model.
AB  - BACKGROUND: Oesophageal perforation is a life-threatening pathology that is
      generally treated conservatively; however, surgical procedures are frequently
      performed. A topical haemostatic agent, Ankaferd Blood Stopper (ABS), also has
      beneficial wound-healing effects. AIMS: This study aimed to determine the effects
      of ABS following experimental oesophageal perforations. STUDY DESIGN: Animal
      experiment. METHODS: The experimental rats were classified into 6 groups (with 7
      rats in each group). Pairs of groups (primary repair alone and primary repair +
      ABS) were terminated in the 1(st), 2(nd), and 3(rd) weeks following injury. The
      oesophageal perforations, which were 8-10 mm in length, were created using a
      nasogastric tube. The perforation sites were repaired with a 6-0 polyglactine
      thread in the primary repair groups. Additionally, ABS was sprayed over the
      perforation site in the treatment groups. Each oesophagus was evaluated
      histopathologically. RESULTS: There were fewer microabscesses and areas of
      necrosis in the ABS groups compared with the primary repair groups. The
      histopathological evaluation revealed that the ABS groups had less inflammation
      and more re-epithelisation compared to the primary repair groups (p=0.002 and
      p=0.003, respectively). Fibrosis in the ABS groups was moderate in the 2(nd) week
      and mild in the 3(rd) week. Comparing the groups with respect to the time
      intervals, only the 1(st) week groups showed a significant difference in terms of
      re-epithelialisation (p=0.044). CONCLUSION: Topical ABS application on the
      repaired experimental oesophageal perforation regions led to positive wound
      healing effects compared with the rats that were administered the primary repair
      alone.

PMID- 25759780
TI  - Comparison of sirolimus and colchicine treatment on the development of peritoneal
      fibrozis in rats having peritoneal dialysis.
AB  - BACKGROUND: Continuous ambulatory peritoneal dialysis is a successful treatment
      modality for patients with end-stage renal disease. Peritoneal fibrosis (PF) is
      the most critical complication of long-term peritoneal dialysis (PD). AIMS: In
      our study, we aimed to compare the effects of colchicine and sirolimus on PF
      induced by hypertonic peritoneal dialysis solutions in rats. STUDY DESIGN: Animal
      experiment. METHODS: Twenty-four rats were randomly divided into three groups.
      The control group received an intraperitoneal injection (ip) of saline. The
      sirolimus group received the PD solution, plus 1.0 mg/kg/day Rapamune(r). The
      colchicine group received the PD solution ip plus 1.0 mg/kg/day of colchicine.
      Blood samples were taken to measure the serum levels of VEGF, TGF-beta, and TNF
      alpha. Peritoneal tissue samples were taken for histopathological evaluation.
      RESULTS: TGF-beta and TNF-alpha values in the sirolimus group were found to be
      statistically significantly lower than in the control and colchicine groups, but
      the differences between the control and colchicine groups were not statistically
      significant. No statistically significant differences were found between the
      groups regarding the VEGF values. Vascular neogenesis and peritoneal thickness
      were compared; the values in the sirolimus group were statistically reduced
      compared to the values in the control group. Mild fibrosis developed in 75% of
      all animals in the sirolimus group; there was no moderate or severe fibrosis
      observed. Fibrosis developed to varying degrees in 100% of the animals in the
      control and colchicine groups. CONCLUSION: The present study demonstrates that
      sirolimus might be beneficial for preventing or delaying the progression of PF
      and neoangiogenesis. These alterations in the peritoneal membrane may be
      connected with reduced TNF-alpha and TGF-beta levels.

PMID- 25759781
TI  - Intramuscular chondroid lipoma: magnetic resonance imaging diagnosis by 'fat ring
      sign'.
AB  - BACKGROUND: Chondroid lipoma is an extremely rare variant of benign lipomatous
      lesions that is composed of lipoblasts, mature fat, and chondroid matrix.
      Although benign lipomatous lesions are the most common soft tissue tumors and
      imaging findings are often pathognomonic, there have been few reports describing
      the imaging features of chondroid lipoma. CASE REPORT: We present magnetic
      resonance imaging (MRI) findings of a pelvic intramuscular chondroid lipoma in a
      59 year-old man and describe a "fat ring sign" that may be useful to diagnose
      this rare tumor radiologically. CONCLUSION: Magnetic resonance imaging findings
      of a chondroid lipoma may be heterogenous according to the distribution of the
      fatty and chondroid tissue. However, in the presence of "fat ring sign,"
      radiologists should consider a diagnosis of chondroid lipoma preoperatively.

PMID- 25759782
TI  - Aberrant carotid artery in the middle ear.
AB  - BACKGROUND: Carotid artery abnormality in the middle ear is a rare clinical
      condition. Recognition of the problems related with this abnormality is important
      since it may mimic vascular tumors. Any intervention with incomplete evaluation
      can be fatal. CASE REPORT: A 23-year-old girl with carotid abnormality and
      sensorineural hearing loss, unsteadiness and tinnitus is presented. She was
      followed for 2 months elsewhere assuming that she had Meniere's disease and had
      previously received some medication for otitis media with effusion. CONCLUSION:
      Tomography and magnetic resonance imaging of the temporal bone are very helpful
      for visualization of an aberrant carotid in the middle ear. Radiological
      presentations are the reduced caliber of the aberrant carotid, an absence of
      cranial opening of carotid canal, tubular coursing along the medial wall of the
      middle ear in continuity with the horizontal carotid canal, dehiscence of the
      lateral carotid plate and enlargement of the tympanic canalicus.

PMID- 25759783
TI  - A Case of Urachal Malacoplakia that Seems Like Urachal Cancer.
AB  - BACKGROUND: Urachal masses observed in adults should be considered malignant
      unless they are confuted. It is very difficult to differentiate between malignant
      or benign lesions, including especially calcified foci and solid areas. CASE
      REPORT: Our case was a 63-year-old male patient who was diagnosed as Behcet's
      Disease 26 years ago. Upon clinical examination, he was also diagnosed with
      adenocarcinoma of prostate. He was examined by computerized tomography to define
      the stage of prostatic adenocarcinoma. The existence of a hypodense multiseptated
      cystic lesion with irregular margins and solid areas located between
      anterosuperior of bladder and umbilicus was reported. Hence, the lesion was
      evaluated as urachal carcinoma and locally advanced prostate cancer by the
      urooncology council. Resection of the mass, partial cystectomy and pelvic
      lymphadenectomy were performed as one of the surgical approach options in urachal
      carcinoma. After pathological examination, the mass was diagnosed as malakoplakia
      and metastasis of prostate adenocarcinoma was also detected in the right
      obdurator lymph nodule. In the literature, case reports of urachal malakoplakia
      are extremely rare. It is also interesting to note the absence of specific
      clinical symptoms for the urachal mass and the existence of concomitant
      adenocarcinoma in our case. CONCLUSION: Malakoplakia can only be diagnosed by
      pathological examination. Particularly, urachal malakoplakia should also be taken
      into consideration in the differential diagnosis of lesions which include solid
      areas and are located in the urachus.

PMID- 25759784
TI  - Management of pleomorphic adenoma in the nasopharynx: a case report.
AB  - BACKGROUND: Pleomorphic adenomas (PAs) are the most common type of benign
      salivary gland tumours and usually originate from the major salivary glands. PA
      originating from the nasopharynx has rarely been reported in the literature. CASE
      REPORT: A 62 year-old male presented with right aural fullness and subjective
      hearing loss. Otoscopic examination revealed an opaque and bulging tympanic
      membrane. Nasal endoscopic examination revealed a smooth mass arising from the
      right wall of the nasopharynx, obstructing the opening of the right Eustachian
      tube. The MRI showed a 1.3*2*1.3 cm sharply outlined and lobar mass in the right
      lateral wall of the nasopharynx. The tumour was meticulously detached from its
      attachment site and excised via the transnasal route under endoscopic
      visualisation. CONCLUSION: We reported pleomorphic adenoma in the nasopharynx in
      a patient who presented with serous otitis media that successfully resected with
      transnasal endoscopic surgery and discussed the treatment methods.

PMID- 25759785
TI  - Relapsing polychondritis: inflamed joints and ears.
AB  - BACKGROUND: Relapsing polychondritis (RP) is an episodic and progressive
      inflammatory disease of the cartilaginous structures, including elastic cartilage
      of the ear and nose, hyaline cartilage of the peripheral joints, fibrocartilage
      at axial sites, and cartilage of the tracheo-bronchial tree. The spectrum of its
      presentations may vary from intermittent mild episodes of chondritis to
      occasional organ involvement or even life-threatening manifestations. CASE
      REPORT: We presented a 64 year-old male patient with bilaterally knee arthritis
      and discoloration of pinna. CONCLUSION: There is lack of awareness about this
      disease due to its rarity. With this case presentation, our goal was to draw
      attention to this disease, which could be delayed for the diagnosis.

PMID- 25759786
TI  - Atypical diabetic ketoacidosis: case report.
AB  - BACKGROUND: Diabetic ketoacidosis (DKA) is a potentially life-threatening
      complication of diabetes mellitus and can lead to death if untreated. It is a
      complex metabolic state characterised by hyperglycaemia, acidosis and ketonuria.
      Bonsai is one of the herbal incense products that contains synthetic cannabinoid
      and can be easily accessible via the internet in many countries. It cannot be
      detected in blood and urine studies using conventional methods. Synthetic
      cannabinoid abuse is associated with severe side effects, including tachycardia,
      high blood pressure, acidosis, excess sedation and coma. CASE REPORT: A 17-year
      old male patient was brought to the emergency department with sudden onset of
      dyspnoea. Laboratory investigations revealed hyperglycaemia, acidosis and
      ketonuria. He was admitted to the intensive care unit with a diagnosis of
      diabetic ketoacidosis. He was not considered a typical case of diabetic
      ketoacidosis because of the tendency to hypokalaemia, persistent tachycardia and
      bronchoscopic findings. We learned from his friends that he had used cannabis for
      a week and used bonzai on the day that he was brought to the emergency service.
      CONCLUSION: Diabetic ketoacidosis with prolonged acidosis and tendency to
      hypokalaemia are investigated for the consumption of synthetic cannabinoids.

PMID- 25759787
TI  - Re-emergent Tongue Tremor as the Presenting Symptom of Parkinson's Disease.
AB  - BACKGROUND: The most common symptom of Parkinson's disease is the unilateral,
      typically resting tremor in body parts, most commonly in the upper extremities.
      However, this finding can spread to the other parts of the body like lips, chin,
      jaw and tongue during the course of the disease. Nevertheless, we have not come
      across any Parkinson's disease case presenting with tongue tremor in the
      literature. CASE REPORT: Here, we present a 58 year-old man with Parkinson's
      disease presenting with tongue tremor, his striking response to the levodopa test
      and his follow-up data. CONCLUSION: The topography of motor symptoms at onset in
      Parkinson's disease is presumably determined by the severity of the Lewy body
      neuronal degeneration in distinct parts of the substantia nigra. Therefore,
      patterns of somatic symptom progression in Parkinson's disease indicate that
      involvement of the cranial structures always follows the development of symptoms
      in the extremities. However, in our case, cranial structures seem to precede the
      involvement of extremity-related areas.

PMID- 25759788
TI  - A Neonatal Case of Phacomatosis Pigmentovascularis Type IIa.

PMID- 25759789
TI  - The inevitable outcome of chronic recurring actinomyces osteomyelitis of the
      hand.

PMID- 25759790
TI  - Daily melatonin levels in women with systemic lupus erythematosus.

PMID- 25759791
TI  - Spontaneous isolated pericardial tamponade associated with warfarin.

PMID- 25759793
TI  - Treating cutaneous T-cell lymphoma with highly irregular surfaces with photon
      irradiation using rice as tissue compensator.
AB  - PURPOSE: Cutaneous T-cell lymphoma (CTCL) is known to have an excellent response
      to radiotherapy, an important treatment modality for this disease. In patients
      with extremity and digit involvement, the irregular surface and depth variations
      create difficulty in delivering a homogenous dose using electrons. We sought to
      evaluate photon irradiation with rice packing as tissue equivalence and determine
      clinical tolerance and response. MATERIALS AND METHODS: Three consecutive CTCL
      patients with extensive lower extremity involvement including the digits were
      treated using external beam photon therapy with rice packing for tissue
      compensation. The entire foot was treated to 30-40 Gy in 2-3 Gy per fraction
      using 6 MV photons prescribed to the mid-plane of an indexed box filled with rice
      in which the foot was placed. Treatment tolerance and response were monitored
      with clinical evaluation. RESULTS: All patients tolerated the treatment without
      treatment breaks. Toxicities included grade 3 erythema and desquamation with
      resolution within 4 weeks. No late toxicities were observed. All patients had a
      partial response by 4 weeks after therapy with two patients achieving a complete
      response. Patients reported improved functionality after treatment. No local
      recurrence has been observed. CONCLUSION: Tissue compensation with rice packing
      offers a convenient, inexpensive, and reproducible method for the treatment of
      CTCL with highly irregular surfaces.

PMID- 25759792
TI  - Misfolded proteins: from little villains to little helpers in the fight against
      cancer.
AB  - The application of cytostatic drugs targeting the high proliferation rates of
      cancer cells is currently the most commonly used treatment option in cancer
      chemotherapy. However, severe side effects and resistance mechanisms may occur as
      a result of such treatment, possibly limiting the therapeutic efficacy of these
      agents. In recent years, several therapeutic strategies have been developed that
      aim at targeting not the genomic integrity and replication machinery of cancer
      cells but instead their protein homeostasis. During malignant transformation, the
      cancer cell proteome develops vast aberrations in the expression of mutated
      proteins, oncoproteins, drug- and apoptosis-resistance proteins, etc. A complex
      network of protein quality-control mechanisms, including chaperoning by heat
      shock proteins (HSPs), not only is essential for maintaining the extravagant
      proteomic lifestyle of cancer cells but also represents an ideal cancer-specific
      target to be tackled. Furthermore, the high rate of protein synthesis and
      turnover in certain types of cancer cells can be specifically directed by
      interfering with the proteasomal and autophagosomal protein recycling and
      degradation machinery, as evidenced by the clinical application of proteasome
      inhibitors. Since proteins with loss of their native conformation are prone to
      unspecific aggregations and have proved to be detrimental to normal cellular
      function, specific induction of misfolded proteins by HSP inhibitors, proteasome
      inhibitors, hyperthermia, or inducers of endoplasmic reticulum stress represents
      a new method of cancer cell killing exploitable for therapeutic purposes. This
      review describes drugs - approved, repurposed, or under investigation - that can
      be used to accumulate misfolded proteins in cancer cells, and particularly
      focuses on the molecular aspects that lead to the cytotoxicity of misfolded
      proteins in cancer cells. 

PMID- 25759794
TI  - Distinct malignant behaviors of mouse myogenic tumors induced by different
      oncogenetic lesions.
AB  - Rhabdomyosarcomas (RMS) are heterogeneous cancers with myogenic differentiation
      features. The cytogenetic and mutational aberrations in RMS are diverse. This
      study examined differences in the malignant behavior of two genetically distinct
      and disease-relevant mouse myogenic tumor models. Kras; p1619(null) myogenic
      tumors, initiated by expression of oncogenic Kras in p16p19(null) mouse satellite
      cells, were metastatic to the lungs of the majority of tumor-bearing animals and
      repopulated tumors in seven of nine secondary recipients. In contrast, SmoM2
      tumors, initiated by ubiquitous expression of a mutant Smoothened allele, did not
      metastasize and repopulated tumors in 2 of 18 recipients only. In summary,
      genetically distinct myogenic tumors in mice exhibit marked differences in
      malignant behavior. 

PMID- 25759795
TI  - The Link between Autoimmunity and Lymphoma: Does NOTCH Signaling Play a
      Contributing Role?
AB  - An association between certain autoimmune conditions and increased risk of
      developing lymphoma is well documented. Recent evidence points to NOTCH signaling
      as a strong driver of autoimmunity. Furthermore, a role for NOTCH in various
      lymphomas, including classical Hodgkin lymphoma, non-Hodgkin lymphoma, and T cell
      lymphoma has also been described. In this mini-review, we will outline what is
      known about involvement of NOTCH signaling in those autoimmune conditions, such
      as rheumatoid arthritis and primary Sjorgren's syndrome, which show an increased
      risk for subsequent diagnosis of lymphoma. Furthermore, we will detail what is
      known about the lymphomas associated with these autoimmune conditions and how
      aberrant or sustained NOTCH signaling in the immune cells that mediate these
      diseases may contribute to lymphoma. 

PMID- 25759796
TI  - CBX7 Expression in Oncocytic Thyroid Neoplastic Lesions (Hurthle Cell Adenomas
      and Carcinomas).
AB  - BACKGROUND: Previous analysis of CBX7 expression in a large number of thyroid
      adenoma and carcinoma samples revealed a progressive reduction of CBX7 levels
      that was well related with the malignant grade of thyroid neoplasias. Hurthle
      cell tumors are unusual thyroid neoplasms characterized by the presence of
      particular cells called oncocytes. OBJECTIVES: In order to develop new tools for
      a more accurate diagnosis of Hurthle cell tumors of the thyroid, we evaluated
      CBX7 protein levels to verify the possible presence of an expression signature.
      METHODS: CBX7 expression was evaluated by immunohistochemistry in a panel of
      thyroid tissue sections including normal thyroids, goiters, follicular adenomas
      and oncocytic lesions. RESULTS: CBX7 expression was low or null in 68% of Hurthle
      adenomas, whereas it was comparable to normal thyroid tissue in Hurthle
      hyperplasias and follicular adenomas. CONCLUSIONS: Reduced expression of CBX7
      suggests a more aggressive identity of Hurthle adenomas with respect to non
      Hurthle ones.

PMID- 25759798
TI  - Novel NKX2-1 Frameshift Mutations in Patients with Atypical Phenotypes of the
      Brain-Lung-Thyroid Syndrome.
AB  - OBJECTIVES: To verify the involvement of NKX2-1 gene in infants with brain-lung
      thyroid (BLT) syndrome and hypothyroid phenotypes variable among congenital
      hypothyroidism (CH) or idiopathic mild hypothyroidism (IMH) of postnatal onset.
      METHODS: The candidates were selected by a case-finding approach in 130 CH and 53
      IMH infants. The NKX2-1 gene was analyzed by direct sequencing and multiplex
      ligation-dependent probe amplification. The variants were studied in vitro, by
      expression analyses and luciferase bioassay. RESULTS: Four cases (3 CH and 1 IMH)
      consistent with BLT syndrome were identified. Two children were affected with
      respiratory distress and CH, but wild-type NKX2-1 gene. The remaining two
      presented choreic movements and no pulmonary involvement, but discrepant thyroid
      phenotypes: one had severe CH with lingual ectopy and the other one IMH with
      gland in situ. They were carriers of new de novo heterozygous frameshift
      mutations of NKX2-1 (c.177delG and c.153_166del14). The c.177delG leads to a
      prematurely truncated protein (p.H60TfsX11) with undetectable activity in vitro.
      The c.153_166del14 leads to the generation of an elongated aberrant protein
      (p.A52RfsX351) able to translocate into the nucleus, but completely inactive on a
      responsive promoter. CONCLUSIONS: Two novel heterozygous frameshift mutations of
      NKX2-1 were identified in 2 cases selected on the basis of a BLT-like phenotype
      among 183 hypothyroid infants. The atypical hypothyroid phenotypes of these 2
      children (CH with lingual ectopy or IMH of postnatal onset) further expand the
      clinical spectrum that can be associated with NKX2-1 mutations.

PMID- 25759797
TI  - Platelet-derived growth factor: a key factor in the pathogenesis of graves'
      ophthalmopathy and potential target for treatment.
AB  - Activation of orbital fibroblasts resulting in excessive proliferation, cytokine
      and hyaluronan production and differentiation into adipocytes, is a main
      determinant of orbital tissue inflammation and tissue expansion in Graves'
      ophthalmopathy (GO). During the last years we have shown that the platelet
      derived growth factor (PDGF) isoforms PDGF-AA, PDGF-AB and PDGF-BB are increased
      in orbital tissue from GO patients with active and inactive disease. These PDGF
      isoforms exhibit the capacity to stimulate proliferation, hyaluronan and
      cytokine/chemokine production by orbital fibroblasts. Moreover, PDGF-AB and PDGF
      BB increase thyroid stimulating hormone receptor (TSHR) expression by orbital
      fibroblasts, which enhances the orbital fibroblast activating capacity of the
      THSR stimulatory autoantibodies present in Graves' disease (GD) patients. Of
      these PDGF isoforms PDGF-BB exhibits the strongest orbital fibroblast activating
      effects, which is likely related to its ability to bind both the PDGF-receptor
      (PDGF-R)alpha and PDGF-Rbeta chains. Thus the PDGF-system fulfills important
      roles in orbital fibroblast activation in both active and inactive GO, which
      supports a therapeutic rationale for blocking PDGF signaling in GO. Tyrosine
      kinase inhibitors (TKIs) may be candidates to target PDGF signaling. Of several
      TKIs tested dasatinib exhibited the highest potency to block PDGF-R signaling in
      orbital fibroblasts and may represent a promising compound for the treatment of
      GO as it was effective at low dosage and is associated with less side effects
      compared to imatinib mesylate and nilotinib. In this review the contribution of
      PDGF to the pathophysiology of GO as well as therapeutic approaches to target
      this PDGF-system will be addressed. 

PMID- 25759799
TI  - Population Reference Values and Prevalence Rates following Universal Screening
      for Subclinical Hypothyroidism during Pregnancy of an Afro-Caribbean Cohort.
AB  - BACKGROUND: Subclinical hypothyroidism (SCH) has been reported to be associated
      with adverse pregnancy outcomes, however universal screening and treatment is
      controversial. OBJECTIVES: Our objectives were to determine population-specific
      pregnancy reference values (R1) for serum thyroid-stimulating hormone (TSH) and
      free thyroxine (FT4) at 14 weeks' gestation, along with the prevalence of SCH and
      thyroid peroxidase antibody (TPOAb). METHODS: This was a prospective hospital
      based cohort study. 1,402 subjects were recruited. Blood samples were obtained
      from 769 singleton pregnancies due to default between recruitment and scheduled
      blood draw. The prevalence of SCH was determined using R1, the laboratory non
      pregnant reference values (R2) and previously recommended pregnancy reference
      values (R3). RESULTS: R1 for TSH and FT4 was 0.03-3.17 mU/l (mean +/- SD, 1.1 +/-
      0.76) and 8.85-17.02 pmol/l (mean +/- SD, 11.96 +/- 2.06), respectively. The
      prevalence of SCH using reference values R1, R2 and R3 was 1.4% (11/769), 0.5%
      (4/769) and 1.9% (15/769). Prevalence was significantly greater using R3 when
      compared to R2 (p = 0.011). TPOAb prevalence was 2.6%. A significantly greater
      prevalence of TPOAb was found in subclinical hypothyroid subjects using all three
      reference values than in euthyroid subjects (~25 vs. 2%, p < 0.05). CONCLUSIONS:
      These reference values are the first to be reported for an Afro-Caribbean
      population. Our findings support the use of pregnancy-specific reference values
      in our population.

PMID- 25759800
TI  - A Conservative Approach Is Reasonable in Patients with Non-Toxic Goitre: Results
      from an Observational Study during 30 Years.
AB  - BACKGROUND: There is a lack of consensus in Europe regarding the management of
      patients with benign goitre. The object of this study was to find out the long
      term results of recommending to patients with clinically and cytologically benign
      non-toxic goitres not to be operated. METHODS: 980 patients were initially
      referred for surgical evaluation due to non-toxic goitre, 508 of whom underwent
      directly thyroidectomy. The remaining 473 patients (median age 56 years) were not
      operated and followed prospectively for a median period of 145 months. RESULTS:
      During follow-up, 38% of the 473 patients were re-referred to the surgeon for a
      new evaluation due to different complaints, mainly growth of the goitre and/or
      worsening of local symptoms. 102 of the 473 patients (22%) had surgery and 27
      (5.7%) developed thyrotoxicosis. 14 patients (3%) were diagnosed with thyroid
      carcinoma, 4 (0.46%) of whom (all elderly women) died of the disease.
      CONCLUSIONS: In patients with non-toxic goitre in whom surgery is not deemed
      necessary at initial evaluation, a conservative approach is reasonable. There is,
      however, a small risk for the development of aggressive carcinomas, and a fourth
      of the patients are operated at a median follow-up of 12 years.

PMID- 25759801
TI  - Patient knowledge of antithyroid drug-induced agranulocytosis.
AB  - BACKGROUND: Agranulocytosis is a serious side effect of antithyroid drugs.
      OBJECTIVE: To ascertain the knowledge of patients and review the quality of
      information available on the internet. METHODS: A questionnaire survey was
      performed for patients receiving antithyroid drugs. Patients attending endocrine
      clinics who were receiving antithyroid drug treatment (group A, n = 33) were
      interviewed. A further national cohort of patients (group B, n = 100) treated
      with antithyroid drugs, participated in an online survey. RESULTS: 60.9% of
      responders were not aware of the common symptoms of agranulocytosis. 18.6% had
      never received any information about side effects. Of the 108 patients who
      recalled receiving information, 30% rated the quality as 'poor' or 'not good at
      all'. Structured interviews of group A patients revealed that almost half (45.5%,
      15/33) had experienced symptoms that could be indicative of agranulocytosis, but
      only 53.3% (8/15) had a blood count checked. A review of 20 selected patient
      information internet sites revealed a significant variation in advice given to
      patients. CONCLUSIONS: Inadequate knowledge about agranulocytosis among patients
      receiving antithyroid drug treatment is common. The available information on the
      internet is variable and inconsistent.

PMID- 25759802
TI  - Cervical lymph nodes, thyroiditis and ophthalmopathy: the pleomorphic face of an
      immunoglobulin g4-related disease.
AB  - We report a case of immunoglobulin G4-related disease (IgG4-RD) presenting with a
      clinical course suggestive of fibrosing thyroiditis and endocrine ophthalmopathy
      associated with enlarged cervical lymph nodes. This clinical presentation should
      prompt a search for associated systemic disorders, including an IgG4-RD. The clue
      to the exact diagnosis of the underlying disease is histological examination
      showing an IgG4 plasmatocytic infiltrate in the inflammatory organs involved. 

PMID- 25759803
TI  - Retrospective Analysis of 255 Papillary Thyroid Carcinomas <=2 cm:
      Clinicohistological Features and Prognostic Factors.
AB  - BACKGROUND: Papillary thyroid carcinoma (PTC) is the most common thyroid cancer.
      The widespread use of neck ultrasound (US) and US-guided fine-needle aspiration
      cytology is triggering an overdiagnosis of PTC. OBJECTIVE: To evaluate clinical
      behavior and outcomes of patients with PTCs <=2 cm, seeking for possible
      prognostic factors. METHODS: Clinical records of cases with histological
      diagnosis of PTC <=2 cm followed at the Endocrine Department of Instituto
      Portugues de Oncologia, Lisbon between 2002 and 2006 were analyzed
      retrospectively. RESULTS: We identified 255 PTCs, 111 were microcarcinomas. Most
      patients underwent near-total thyroidectomy, with lymph node dissections in 55
      cases (21.6%). Radioiodine therapy was administered in 184 patients. At the last
      evaluation, 38 (14.9%) had evidence of disease. Two deaths were attributed to
      PTC. Median (+/-SD) follow-up was 74 (+/-23) months. Multivariate analysis
      identified vascular invasion, lymph node and systemic metastases significantly
      associated with recurrence/persistence of disease. In addition, lymph node
      involvement was significantly associated with extrathyroidal extension and
      angioinvasion. Median (+/-SD) disease-free survival (DFS) was estimated as 106
      (+/-3) months and the 5-year DFS rate was 87.5%. Univariate Cox analysis
      identified some relevant parameters for DFS, but multivariate regression only
      identified lymph node and systemic metastases as significant independent factors.
      The median DFS estimated for lymph node and systemic metastases was 75 and 0
      months, respectively. CONCLUSIONS: In the setting of small PTCs, vascular
      invasion, extrathyroidal extension and lymph node and/or systemic metastases may
      confer worse prognosis, perhaps justifying more aggressive therapeutic and follow
      up approaches in such cases.

PMID- 25759804
TI  - Recombinant human thyroid-stimulating hormone-aided remnant ablation achieves a
      response to treatment comparable to that with thyroid hormone withdrawal in
      patients with clinically relevant lymph node metastases.
AB  - It has already been shown that remnant ablation in patients with thyroid cancer
      and lymph node (LN) metastases has similar results when patients are prepared
      after recombinant human thyroid-stimulating hormone (rhTSH) therapy or thyroid
      hormone withdrawal (THW). Due to the current changes in the risk-of-recurrence
      classifications, we decided to evaluate the initial response to treatment and the
      outcome at medium-term follow-up in 40 consecutive patients with clinically
      relevant lymph nodes who received radioiodine remnant ablation after rhTSH
      therapy (n = 20) or THW (n = 20). Each patient received either 100 or 150 mCi 131
      I for ablation based on TNM status, and the mean amounts of 131-I used in the 2
      groups were not significantly different. An excellent response to treatment was
      observed in 45% of the patients prepared after rhTSH therapy compared to 20% of
      those prepared after THW (p = 0.08). Three patients (2 in the THW group and 1 in
      the rhTSH group) who had N1a in the initial surgery presented with structural
      persistence as an initial response to treatment. One patient in the THW group had
      a follow-up of the persistent disease with no surgical treatment, and 2 others
      received a lateral LN dissection. When the status at final follow-up was
      considered (median follow-up 3.3 years, range 3-4.2), 60% of the patients ablated
      after rhTSH therapy were considered with no evidence of disease, compared to 30%
      of those who underwent THW. The frequency of structural persistence (metastatic
      LN) was similar in the 2 groups (15 vs. 25%), and the distribution of the
      responses at final follow-up was not statistically significantly different (p =
      0.12). We conclude that preparation after rhTSH therapy seems to be as effective
      as after THW for patients with clinically relevant LN metastases. 

PMID- 25759805
TI  - Tandem Germline RET Mutations in a Family Pathogenetic for Multiple Endocrine
      Neoplasia 2B, Confirmed by a Natural Experiment.
AB  - A family with germline tandem V804M/Y806C mutations in the RET proto-oncogene was
      reported. The in vitro study results showing that these mutations were on the
      same allele and that RET with these mutations had a moderate transforming
      activity were confirmed by the clinical features of the offspring as a natural
      experiment. Thus, the tandem double RET mutations are pathogenetic for MEN 2B. 

PMID- 25759806
TI  - Anaplastic carcinoma and toxic multinodular goiter: an unusual presentation.
AB  - A 70-year-old male was referred with hyperthyroidism and multinodular goiter
      (MNG). Thyroid ultrasonography showed 2 nodules, one in the isthmus and the other
      in the left lobe, 51 and 38 mm in diameter, respectively. Neck CT showed a large
      MNG, thyroid scintigraphy showed increased uptake in the nodule in the left lobe,
      and fine-needle aspiration biopsy showed a benign cytology of the nodule in the
      isthmus. The patient declined surgery and was treated with methimazole. After
      being lost to follow-up for 3 years, the patient returned with complaints of
      dyspnea, dysphagia, and hoarseness; he was still hyperthyroid. Cervical CT showed
      a large mass in the isthmus and left lobe with invasion of surrounding tissues,
      the trachea, the esophagus, and the recurrent laryngeal nerve. Bronchoscopy
      showed extensive infiltration and compression of the trachea to 20% of its
      caliber. A tracheal biopsy revealed an anaplastic thyroid carcinoma. The tumor
      was considered unresectable, and radiotherapy was given. One month later, the
      patient died. The association between a toxic thyroid nodule and anaplastic
      thyroid carcinoma has apparently not been reported so far. 

PMID- 25759807
TI  - A bioinformatic survey of distribution, conservation, and probable functions of
      LuxR solo regulators in bacteria.
AB  - LuxR solo transcriptional regulators contain both an autoinducer binding domain
      (ABD; N-terminal) and a DNA binding Helix-Turn-Helix domain (HTH; C-terminal),
      but are not associated with a cognate N-acyl homoserine lactone (AHL) synthase
      coding gene in the same genome. Although a few LuxR solos have been
      characterized, their distributions as well as their role in bacterial signal
      perception and other processes are poorly understood. In this study we have
      carried out a systematic survey of distribution of all ABD containing LuxR
      transcriptional regulators (QS domain LuxRs) available in the InterPro database
      (IPR005143), and identified those lacking a cognate AHL synthase. These LuxR
      solos were then analyzed regarding their taxonomical distribution, predicted
      functions of neighboring genes and the presence of complete AHL-QS systems in the
      genomes that carry them. Our analyses reveal the presence of one or multiple
      predicted LuxR solos in many proteobacterial genomes carrying QS domain LuxRs,
      some of them harboring genes for one or more AHL-QS circuits. The presence of
      LuxR solos in bacteria occupying diverse environments suggests potential
      ecological functions for these proteins beyond AHL and interkingdom signaling.
      Based on gene context and the conservation levels of invariant amino acids of
      ABD, we have classified LuxR solos into functionally meaningful groups or
      putative orthologs. Surprisingly, putative LuxR solos were also found in a few
      non-proteobacterial genomes which are not known to carry AHL-QS systems. Multiple
      predicted LuxR solos in the same genome appeared to have different levels of
      conservation of invariant amino acid residues of ABD questioning their binding to
      AHLs. In summary, this study provides a detailed overview of distribution of LuxR
      solos and their probable roles in bacteria with genome sequence information.

PMID- 25759808
TI  - Health-based audible noise guidelines account for infrasound and low-frequency
      noise produced by wind turbines.
AB  - Setbacks for wind turbines have been established in many jurisdictions to address
      potential health concerns associated with audible noise. However, in recent
      years, it has been suggested that infrasound (IS) and low-frequency noise (LFN)
      could be responsible for the onset of adverse health effects self-reported by
      some individuals living in proximity to wind turbines, even when audible noise
      limits are met. The purpose of this paper was to investigate whether current
      audible noise-based guidelines for wind turbines account for the protection of
      human health, given the levels of IS and LFN typically produced by wind turbines.
      New field measurements of indoor IS and outdoor LFN at locations between 400 and
      900 m from the nearest turbine, which were previously underrepresented in the
      scientific literature, are reported and put into context with existing published
      works. Our analysis showed that indoor IS levels were below auditory threshold
      levels while LFN levels at distances >500 m were similar to background LFN
      levels. A clear contribution to LFN due to wind turbine operation (i.e., measured
      with turbines on in comparison to with turbines off) was noted at a distance of
      480 m. However, this corresponded to an increase in overall audible sound
      measures as reported in dB(A), supporting the hypothesis that controlling audible
      sound produced by normally operating wind turbines will also control for LFN.
      Overall, the available data from this and other studies suggest that health-based
      audible noise wind turbine siting guidelines provide an effective means to
      evaluate, monitor, and protect potential receptors from audible noise as well as
      IS and LFN. 

PMID- 25759809
TI  - Antibiotic Resistance: What are the Opportunities for Primary Care in Alleviating
      the Crisis?
AB  - Numerous opportunities are available in primary care for alleviating the crisis
      of increasing antibiotic resistance. Preventing patients from developing an acute
      respiratory infection (ARI) will obviate any need for antibiotic use downstream.
      Hygiene measures such as physical barriers and hand hygiene, and possibly
      vaccination and exercise, may be effective. Also, a large range of complementary
      and alternative medicines (e.g. zinc, vitamin C and probiotics) are proposed for
      preventing and treating ARIs, but evidence for efficacy is scarce. General
      practitioners' (GPs) attitudes towards antibiotic prescribing are a major factor
      in the prescribing for ARIs. Professional interventions with educational
      components are effective, although they have modest effects, and are expensive.
      GPs' perceptions - that mistakenly assume as a default that patients want
      antibiotics for their ARIs - are often wrong. Shared decision making might be a
      solution, as it enables clinician and patient to participate jointly in making a
      health decision, having discussed the options together with the evidence for
      their harms as well as benefits. Furthermore, GPs' diagnostic uncertainty - often
      leading to an antibiotic prescription "just in case" - might be addressed by
      exploiting strategies such as safety-netting, e.g., establishing with the patient
      a priori clearly defined actions to take if the course of the illness deviates
      from the expected. None of these strategies or interventions on their own will
      greatly improve the use of antibiotics for ARIs. However, used in concert,
      combinations are likely to enable clinicians and health care systems to implement
      the strategies that will reduce antimicrobial resistance in the future. 

PMID- 25759810
TI  - Knowledge in the Investigation of A-to-I RNA Editing Signals.
AB  - RNA editing is a post-transcriptional alteration of RNA sequences that is able to
      affect protein structure as well as RNA and protein expression. Adenosine-to
      inosine (A-to-I) RNA editing is the most frequent and common post-transcriptional
      modification in human, where adenosine (A) deamination produces its conversion
      into inosine (I), which in turn is interpreted by the translation and splicing
      machineries as guanosine (G). The disruption of the editing machinery has been
      associated to various human diseases such as cancer or neurodegenerative
      diseases. This biological phenomenon is catalyzed by members of the adenosine
      deaminase acting on RNA (ADAR) family of enzymes and occurs on dsRNA structures.
      Despite the enormous efforts made in the last decade, the real biological
      function underlying such a phenomenon, as well as ADAR's substrate features still
      remain unknown. In this work, we summarize the major computational aspects of
      predicting and understanding RNA editing events. We also investigate the
      detection of short motif sequences potentially characterizing RNA editing signals
      and the use of a logistic regression technique to model a predictor of RNA
      editing events. The latter, named AIRlINER, an algorithmic approach to assessment
      of A-to-I RNA editing sites in non-repetitive regions, is available as a web app
      at: http://alpha.dmi.unict.it/airliner/. Results and comparisons with the
      existing methods encourage our findings on both aspects. 

PMID- 25759811
TI  - Promoting Coordinated Development of Community-Based Information Standards for
      Modeling in Biology: The COMBINE Initiative.
AB  - The Computational Modeling in Biology Network (COMBINE) is a consortium of groups
      involved in the development of open community standards and formats used in
      computational modeling in biology. COMBINE's aim is to act as a coordinator,
      facilitator, and resource for different standardization efforts whose domains of
      use cover related areas of the computational biology space. In this perspective
      article, we summarize COMBINE, its general organization, and the community
      standards and other efforts involved in it. Our goals are to help guide readers
      toward standards that may be suitable for their research activities, as well as
      to direct interested readers to relevant communities where they can best expect
      to receive assistance in how to develop interoperable computational models. 

PMID- 25759812
TI  - Long-term outcomes of microsurgical nasal replantation: review of the literature
      and illustrated 10-year follow-up of a pediatric case with full sensory recovery.
AB  - We present a case of successful artery only total nose replantation in an 18
      month-old child, with 10 years of follow-up and full sensory recovery despite no
      nerve repair. The common absence of veins for anastomosis does not prevent
      successful replant, as demonstrated with the use of Hirudo medicinalis use in
      this unique case. We comprehensively review the literature of this rare and
      complex injury and advocate microsurgical replantation where possible over other
      methods of nasal reconstruction. 

PMID- 25759813
TI  - The cell birth marker BrdU does not affect recruitment of subsequent cell
      divisions in the adult avian brain.
AB  - BrdU is commonly used to quantify neurogenesis but also causes mutation and has
      mitogenic, transcriptional, and translational effects. In mammalian studies,
      attention had been given to its dosage, but in birds such examination was not
      conducted. Our previous study suggested that BrdU might affect subsequent cell
      divisions and neuronal recruitment in the brain. Furthermore, this effect seemed
      to increase with time from treatment. Accordingly, we examined whether BrdU might
      alter neurogenesis in the adult avian brain. We compared recruitment of [(3)H]
      thymidine(+) neurons in brains of zebra finches (Taeniopygia guttata) when no
      BrdU was involved and when BrdU was given 1 or 3 months prior to [(3)H]
      thymidine. In nidopallium caudale, HVC, and hippocampus, no differences were
      found between groups in densities and percentages of [(3)H]-thymidine(+) neurons.
      The number of silver grains per [(3)H]-thymidine(+) neuronal nucleus and their
      distribution were similar across groups. Additionally, time did not affect the
      results. The results indicate that the commonly used dosage of BrdU in birds has
      no long-term effects on subsequent cell divisions and neuronal recruitment. This
      conclusion is also important in neuronal replacement experiments, where BrdU and
      another cell birth marker are given, with relatively long intervals between them.

PMID- 25759814
TI  - Navigation of pedicle screws in the thoracic spine with a new electromagnetic
      navigation system: a human cadaver study.
AB  - INTRODUCTION: Posterior stabilization of the spine is a standard procedure in
      spinal surgery. In addition to the standard techniques, several new techniques
      have been developed. The objective of this cadaveric study was to examine the
      accuracy of a new electromagnetic navigation system for instrumentation of
      pedicle screws in the spine. MATERIAL AND METHOD: Forty-eight pedicle screws were
      inserted in the thoracic spine of human cadavers using EMF navigation and
      instruments developed especially for electromagnetic navigation. The screw
      position was assessed postoperatively by a CT scan. RESULTS: The screws were
      classified into 3 groups: grade 1 = ideal position; grade 2 = cortical
      penetration <2 mm; grade 3 = cortical penetration >=2 mm. The initial evaluation
      of the system showed satisfied positioning for the thoracic spine; 37 of 48
      screws (77.1%, 95% confidence interval [62.7%, 88%]) were classified as group 1
      or 2. DISCUSSION: The screw placement was satisfactory. The initial results show
      that there is room for improvement with some changes needed. The ease of use and
      short setup times should be pointed out. Instrumentation is achieved without
      restricting the operator's mobility during navigation. CONCLUSION: The results
      indicate a good placement technique for pedicle screws. Big advantages are the
      easy handling of the system.

PMID- 25759815
TI  - Evaluation of hemagglutination activity of chitosan nanoparticles using human
      erythrocytes.
AB  - Chitosan is a polysaccharide composed of randomly distributed chains of beta-(1
      4) D-glucosamine and N-acetyl-D-glucosamine. This compound is obtained by partial
      or total deacetylation of chitin in acidic solution. The chitosan-based
      hemostatic agents have been gaining much attention in the management of bleeding.
      The aim of this study was to evaluate in vitro hemagglutination activity of
      chitosan nanoparticles using human erythrocytes. The preparation of nanoparticles
      was achieved by ionotropic gelification technique followed by neutralization with
      NaOH 1 mol/L(-1). The hemagglutination activity was performed on a solution of 2%
      erythrocytes (pH 7.4 on PBS) collected from five healthy volunteers. The
      hemolysis determination was made by spectrophotometric analysis. Chitosan
      nanoparticle solutions without NaOH addition changed the reddish colour of the
      wells into brown, suggesting an oxidative reaction of hemoglobin and possible
      cell lysis. All neutralized solutions of chitosan nanoparticles presented
      positive haemagglutination, without any change in reaction color. Chitosan
      nanoparticles presented hemolytic activity ranging from 186.20 to 223.12%, while
      neutralized solutions ranged from 2.56 to 72.54%, comparing to distilled water.
      Results highlight the need for development of new routes of synthesis of chitosan
      nanoparticles within human physiologic pH. 

PMID- 25759816
TI  - Tetramethylpyrazine enhances vascularization and prevents osteonecrosis in
      steroid-treated rats.
AB  - Steroid-induced osteonecrosis of the femoral head (steroid-induced ONFH) is an
      avascular necrosis disease of bone. Tetramethylpyrazine (TMP), with significant
      vascular protective properties, has been widely used for the treatments of
      ischemic neural disorders and cardiovascular diseases. However, its role in the
      treatment of steroid-induced ONFH has not been evaluated. In this study, our
      results showed that TMP significantly decreased the ratio of empty lacuna,
      adipose tissue area, and adipocyte perimeter in steroid-induced ONFH rats
      histopathologically. TMP also reduced the levels of serum lipid dramatically by
      haematological examination. According to the micro-CT quantification, TMP could
      improve the microstructure of the trabecular bone and increases bone mineral
      density in steroid-induced ONFH rats. Moreover, TMP significantly increased the
      vessel volume, vessel surface, percentage of vessel volume, and vessel thickness
      of the femoral heads by micro-CT. Interestingly, the downregulation of VEGF and
      FLK1 proteins in the sera and necrotic femoral heads could be reversed by TMP
      treatment, and this was true for their mRNA expressions in femoral heads. In
      conclusion, these findings suggest for the first time that TMP may prevent
      steroid-induced ONFH and also enhance femoral head vascularization by inhibiting
      the effect of steroid on VEGF/FLK1 signal pathway. 

PMID- 25759817
TI  - RNA-based TWIST1 inhibition via dendrimer complex to reduce breast cancer cell
      metastasis.
AB  - Breast cancer is the leading cause of cancer-related deaths among women in the
      United States, and survival rates are lower for patients with metastases and/or
      triple-negative breast cancer (TNBC; ER, PR, and Her2 negative). Understanding
      the mechanisms of cancer metastasis is therefore crucial to identify new
      therapeutic targets and develop novel treatments to improve patient outcomes. A
      potential target is the TWIST1 transcription factor, which is often overexpressed
      in aggressive breast cancers and is a master regulator of cellular migration
      through epithelial-mesenchymal transition (EMT). Here, we demonstrate an siRNA
      based TWIST1 silencing approach with delivery using a modified poly(amidoamine)
      (PAMAM) dendrimer. Our results demonstrate that SUM1315 TNBC cells efficiently
      take up PAMAM-siRNA complexes, leading to significant knockdown of TWIST1 and EMT
      related target genes. Knockdown lasts up to one week after transfection and leads
      to a reduction in migration and invasion, as determined by wound healing and
      transwell assays. Furthermore, we demonstrate that PAMAM dendrimers can deliver
      siRNA to xenograft orthotopic tumors and siRNA remains in the tumor for at least
      four hours after treatment. These results suggest that further development of
      dendrimer-based delivery of siRNA for TWIST1 silencing may lead to a valuable
      adjunctive therapy for patients with TNBC. 

PMID- 25759819
TI  - Endophytic Bacillus subtilis strain E1R-J is a promising biocontrol agent for
      wheat powdery mildew.
AB  - In this study, the biocontrol efficacies of 14 endophytic bacterial strains were
      tested against Blumeria graminis f. sp. tritici (Bgt) in pot experiments under
      greenhouse conditions. Bacillus subtilis strain E1R-j significantly reduced
      disease index and exhibited the best control (90.97%). When different
      formulations of E1R-j were sprayed 24 h before Bgt inoculation, fermentation
      liquid without bacterial cell and crude protein suspension displayed the similar
      effects; and they reduced disease index more than bacterial cell suspension
      (10(9) cfu mL(-1)) and fermentation liquid without protein. The control effects
      were not significantly different between 10(11) and 10(9) cfu mL(-1) of bacterial
      cell suspension but were higher than 10(7) cfu mL(-1). Further observations
      showed that conidial germination and appressorial formation of Bgt were retarded
      by spraying E1R-j 24 h before Bgt inoculation. Compared with the water check,
      conidial germination and appressorial formation were decreased by 43.3% and
      42.7%, respectively. In the treatment with E1R-j, the number of houstoria
      significantly reduced and the speed of mycelial extension was slowed down in the
      wheat leaves. Scanning electron microscopy observation revealed that E1R-j
      significantly suppressed the conidial germination and caused rupture and
      deformation of germ tubes. On the surface of wheat leaves, mycelia and
      conidiophores became shrinking. 

PMID- 25759818
TI  - DNaseI protects against Paraquat-induced acute lung injury and pulmonary fibrosis
      mediated by mitochondrial DNA.
AB  - BACKGROUND: Paraquat (PQ) poisoning is a lethal toxicological challenge that
      served as a disease model of acute lung injury and pulmonary fibrosis, but the
      mechanism is undetermined and no effective treatment has been discovered. METHODS
      AND FINDINGS: We demonstrated that PQ injures mitochondria and leads to mtDNA
      release. The mtDNA mediated PBMC recruitment and stimulated the alveolar
      epithelial cell production of TGF-beta1 in vitro. The levels of mtDNA in
      circulation and bronchial alveolar lavage fluid (BALF) were elevated in a mouse
      of PQ-induced lung injury. DNaseI could protect PQ-induced lung injury and
      significantly improved survival. Acute lung injury markers, such as TNFalpha, IL
      1beta, and IL-6, and marker of fibrosis, collagen I, were downregulated in
      parallel with the elimination of mtDNA by DNaseI. These data indicate a possible
      mechanism for PQ-induced, mtDNA-mediated lung injury, which may be shared by
      other causes of lung injury, as suggested by the same protective effect of DNaseI
      in bleomycin-induced lung injury model. Interestingly, increased mtDNA in the
      BALF of patients with amyopathic dermatomyositis-interstitial lung disease can be
      appreciated. CONCLUSIONS: DNaseI targeting mtDNA may be a promising approach for
      the treatment of PQ-induced acute lung injury and pulmonary fibrosis that merits
      fast tracking through clinical trials.

PMID- 25759820
TI  - Gene profiling of bone around orthodontic mini-implants by RNA-sequencing
      analysis.
AB  - This study aimed to evaluate the genes that were expressed in the healing bones
      around SLA-treated titanium orthodontic mini-implants in a beagle at early (1
      week) and late (4-week) stages with RNA-sequencing (RNA-Seq). Samples from sites
      of surgical defects were used as controls. Total RNA was extracted from the
      tissue around the implants, and an RNA-Seq analysis was performed with Illumina
      TruSeq. In the 1-week group, genes in the gene ontology (GO) categories of cell
      growth and the extracellular matrix (ECM) were upregulated, while genes in the
      categories of the oxidation-reduction process, intermediate filaments, and
      structural molecule activity were downregulated. In the 4-week group, the genes
      upregulated included ECM binding, stem cell fate specification, and
      intramembranous ossification, while genes in the oxidation-reduction process
      category were downregulated. GO analysis revealed an upregulation of genes that
      were related to significant mechanisms, including those with roles in cell
      proliferation, the ECM, growth factors, and osteogenic-related pathways, which
      are associated with bone formation. From these results, implant-induced bone
      formation progressed considerably during the times examined in this study. The
      upregulation or downregulation of selected genes was confirmed with real-time
      reverse transcription polymerase chain reaction. The RNA-Seq strategy was useful
      for defining the biological responses to orthodontic mini-implants and
      identifying the specific genetic networks for targeted evaluations of successful
      peri-implant bone remodeling. 

PMID- 25759821
TI  - Evaluation of deformable image registration methods for dose monitoring in head
      and neck radiotherapy.
AB  - In the context of head and neck cancer (HNC) adaptive radiation therapy (ART),
      the two purposes of the study were to compare the performance of multiple
      deformable image registration (DIR) methods and to quantify their impact for dose
      accumulation, in healthy structures. Fifteen HNC patients had a planning computed
      tomography (CT0) and weekly CTs during the 7 weeks of intensity-modulated
      radiation therapy (IMRT). Ten DIR approaches using different registration methods
      (demons or B-spline free form deformation (FFD)), preprocessing, and similarity
      metrics were tested. Two observers identified 14 landmarks (LM) on each CT-scan
      to compute LM registration error. The cumulated doses estimated by each method
      were compared. The two most effective DIR methods were the demons and the FFD,
      with both the mutual information (MI) metric and the filtered CTs. The
      corresponding LM registration accuracy (precision) was 2.44 mm (1.30 mm) and 2.54
      mm (1.33 mm), respectively. The corresponding LM estimated cumulated dose
      accuracy (dose precision) was 0.85 Gy (0.93 Gy) and 0.88 Gy (0.95 Gy),
      respectively. The mean uncertainty (difference between maximal and minimal dose
      considering all the 10 methods) to estimate the cumulated mean dose to the
      parotid gland (PG) was 4.03 Gy (SD = 2.27 Gy, range: 1.06-8.91 Gy). 

PMID- 25759822
TI  - A comparative evaluation of a novel vaccine in APP/PS1 mouse models of
      Alzheimer's disease.
AB  - Immunization against amyloid-beta-peptide (Abeta) has been widely investigated as
      a potential immunotherapeutic approach for Alzheimer's disease (AD). With the aim
      of developing an active immunogenic vaccine without need of coadjuvant
      modification for human trials and therefore avoiding such side effects, we
      designed the Abeta 1-42 vaccine (EB101), delivered in a liposomal matrix, that
      based on our previous studies significantly prevents and reverses the AD
      neuropathology, clearing Abeta plaques while markedly reducing neuronal
      degeneration, behavioral deficits, and minimizing neuroinflammation in APP/PS1
      transgenic mice. Here, the efficacy of our immunogenic vaccine EB101 was compared
      with the original immunization vaccine cocktail Abeta 42 + CFA/IFA (Freund's
      adjuvant), in order to characterize the effect of sphingosine-1-phosphate (S1P)
      in the immunotherapeutic response. Quantitative analysis of amyloid burden showed
      a notable decrease in the neuroinflammation reaction against Abeta plaques when
      S1P was compared with other treatments, suggesting that S1P plays a key role as a
      neuroprotective agent. Moreover, EB101 immunized mice presented a protective
      immunogenic reaction resulting in the increase of Abeta-specific antibody
      response and decrease of reactive glia in the affected brain areas, leading to a
      Th2 immunological reaction. 

PMID- 25759823
TI  - Intramyocardial hemorrhage: an enigma for cardiac MRI?
AB  - Cardiovascular magnetic resonance (CMR) is a useful noninvasive technique for
      determining the presence of microvascular obstruction (MVO) and intramyocardial
      hemorrhage (IMH), frequently occurring in patients after reperfused myocardial
      infarction (MI). MVO, or the so-called no-reflow phenomenon, is associated with
      adverse ventricular remodeling and a poor prognosis during follow-up. Similarly,
      IMH is considered a severe damage after revascularization by percutaneous primary
      coronary intervention (PPCI) or fibrinolysis, which represents a worse prognosis.
      However, the pathophysiology of IMH is not fully understood and imaging
      modalities might help to better understand that phenomenon. While, during the
      past decade, several studies examined the distribution patterns of late
      gadolinium enhancement with different CMR sequences, the standardized CMR
      protocol for assessment of IMH is not yet well established. The aim of this
      review is to evaluate the available literature on this issue, with particular
      regard to CMR sequences. New techniques, such as positron emission
      tomography/magnetic resonance imaging (PET/MRI), could be useful tools to explore
      molecular mechanisms of the myocardial infarction healing process. 

PMID- 25759824
TI  - Characterisation of pain responses in the high fat diet/streptozotocin model of
      diabetes and the analgesic effects of antidiabetic treatments.
AB  - Chronic pain is a common complication of diabetes. The aim of the present study
      was to characterise pain behaviour in a high fat diet/streptozotocin (HFD/STZ)
      model of diabetes in the rat, investigate spinal mechanisms, and determine the
      effects of antidiabetic interventions. Three-week consumption of a high fat diet
      followed by single injection of STZ (45 mgkg(-1)) produced sustained changes in
      plasma insulin and glucose until day 120. Hindpaw mechanical withdrawal
      thresholds were significantly lowered in the model, but mechanically evoked
      responses of spinal neurones were unaltered, compared to HFD/vehicle rats.
      HFD/STZ rats had significantly lower numbers of spinal Iba-1 positive cells
      (morphologically identified as activated microglia) and spinal GFAP
      immunofluorescence (a marker of astrogliosis) in the spinal cord at day 50,
      compared to time-matched controls. The PPARgamma ligand pioglitazone (10 mgkg(
      1)) did not alter HFD/STZ induced metabolic changes or hindpaw withdrawal
      thresholds of HFD/STZ rats. Daily linagliptin (3 mgkg(-1)) and metformin (200
      mgkg(-1)) from day 4 after model induction did not alter plasma glucose or
      insulin in HFD/STZ rats but significantly prevented changes in the mechanical
      withdrawal thresholds. The demonstration that currently prescribed antidiabetic
      drugs prevent aberrant pain behaviour supports the use of this model to
      investigate pain mechanisms associated with diabetes. 

PMID- 25759825
TI  - GK-1 improves the immune response induced by bone marrow dendritic cells loaded
      with MAGE-AX in mice with melanoma.
AB  - The aim of dendritic cell (DC) vaccination in cancer is to induce tumor-specific
      effector T cells that may reduce and control tumor mass. Immunostimulants that
      could drive a desired immune response are necessary to be found in order to
      generate a long lasting tumor immune response. GK-1 peptide, derived from Taenia
      crassiceps, induces not only increase in TNFalpha, IFNgamma, and MCP-1 production
      in cocultures of DCs and T lymphocytes but also immunological protection against
      influenza virus. Moreover, the aim of this investigation is the use of GK-1 as a
      bone marrow DCs (BMDCs) immunostimulant targeted with MAGE antigen; thus, BMDC
      may be used as immunotherapy against murine melanoma. GK-1 induced in BMDCs a
      meaningful increment of CD86 and IL-12. In addition, the use of BMDCs TNFalpha/GK
      1/MAGE-AX induced the highest survival and the smallest tumors in mice. Besides,
      the treatment helped to increase CD8 lymphocytes levels and to produce IFNgamma
      in lymph nodes. Moreover, the histopathological analysis showed that BMDCs
      treated with GK-1/TNFalpha and loaded with MAGE-AX induced the apparition of more
      apoptotic and necrotic areas in tumors than in mice without treatment. These
      results highlight the properties of GK-1 as an immunostimulant of DCs and suggest
      as a potential candidate the use of this immunotherapy against cancer disease. 

PMID- 25759826
TI  - Polymorphisms of tumor necrosis factor-alpha, transforming growth factor-beta,
      and interleukin-10 in asthma associated with olive pollen sensitization.
AB  - Sensitization to specific olive pollen-allergens (Ole e 2 and 10) has been
      correlated with a clinical pattern of asthma. This study analyzes the association
      between several polymorphims of TNFA (G-308A, C-857T, and C-1031T), IL10 (C-571A
      and A-1117G), and TGFB (C-509-T) and these sensitizations. These polymorphisms
      were genotyped by allelic discrimination, in olive pollen-allergic patients
      (phenotyped for specific Ole e 2 and 10 sensitizations) and healthy controls.
      Levels of serum-soluble cytokines were correlated with specific genotypes and
      clinical phenotypes. The results showed that heterozygous TGFB C-509T genotype,
      besides having the lowest sera TGF- levels, was significantly increased in olive
      pollen-allergic patients compared with controls. According specific
      sensitizations, CC genotype of IL10 C-571A could be a protective factor for Ole e
      2 sensitization and mainly for asthmatic Ole e 2 sensitized patients compared
      with asthmatic non-Ole e 2 sensitized patients (OR: 0.26, P = 0.008). In
      contrast, heterozygous CA genotype was increased in Ole e 2 asthmatic subjects
      compared to asthmatic non-Ole e 2 sensitized patients. Lastly, heterozygous TNFA
      G-308A genotype was associated with Ole e 10 sensitization (OR: 2.5, P = 0.04).
      In conclusion, these results suggest a role of TGF-beta1 in olive-pollen
      sensitization and TNF-alpha and IL-10 genotypes in the asthma induced by specific
      olive-pollen allergens. 

PMID- 25759827
TI  - Expression of TNF-alpha, APRIL and BCMA in Behcet's disease.
AB  - BACKGROUND: Tumor necrosis factor-alpha (TNF-alpha) is an important
      proinflammatory cytokine which plays an important role in the immunopathogenesis
      of Behcet's disease (BD). B cell activating factor (BAFF) and its homolog A
      proliferation inducing ligand (APRIL) are members of the tumor necrosis factor
      family. BAFF binds to 3 receptors, B cell activating factor receptor (BAFF-R),
      transmembrane activator and calcium modulator ligand interactor (TACI), and B
      cell maturation antigen (BCMA) that are expressed by B cells. OBJECTIVE:
      Estimation of the serum levels of TNF-alpha, APRIL, BAFF, and BCMA in patients
      with BD in an effort to evaluate their degree of involvement in the pathogenesis
      and development of BD. PATIENTS AND METHODS: This study included 30 male patients
      fulfilling the international study group criteria for the diagnosis of BD. Twenty
      age-matched healthy male volunteers served as control. Serum samples were used
      for quantification of TNF-alpha, APRIL, BCMA, BAFF, and hsCRP using ELISA
      techniques. RESULTS: The mean serum levels of TNF-alpha, APRIL, BCMA, and BAFF
      were more elevated in cases than in controls in a statistically significant
      manner (P < 0.001). Positive correlation was observed between hs-CRP and BDCAF
      (Behcet's disease current activity forum) index (r 0.68, P < 0.001). None of the
      TNF family members tested was affected by a positive pathergy test. CONCLUSIONS:
      Patients have significantly higher levels of TNF family members' (TNF-alpha,
      BAFF, APRIL, and BCMA) compared to controls which might contribute to the
      pathogenesis of BD.

PMID- 25759829
TI  - Serum levels of TNF-alpha, IL-12/23p40, and IL-17 in plaque psoriasis and their
      correlation with disease severity.
AB  - A case-control study was performed to assess the serum levels of TNF-alpha, IL
      12/23p40, and IL-17 in patients with plaque psoriasis, compare them with healthy
      controls, and correlate them with disease severity, as represented by Psoriasis
      Area Severity Index (PASI). 32 consecutively selected, untreated patients with
      active, chronic plaque psoriasis were recruited and compared to 32 age- and sex
      matched healthy controls. Serum cytokine levels were determined by solid phase
      sandwich enzyme linked immunosorbent assay (R&D Systems Europe, Ltd.). The mean
      serum levels of TNF-alpha were significantly higher in psoriatic patients
      compared to those of controls (Mann-Whitney U test; P = 0.000). However, the
      median serum levels of neither IL-12/23p40 nor IL-17 differ significantly between
      the 2 groups (Mann-Whitney U test; P = 0.968 and P = 0.311, resp.). No
      significant correlations were found between PASI and any of the cytokine serum
      levels (Spearman's rank test; P > 0.05). Despite the well-evidenced therapeutic
      efficacy of biologic agents targeting TNF-alpha, IL-12/23p40, and IL-17, serum
      levels of TNF-alpha, IL-12/23p40, and IL-17 do not seem to correlate with the
      severity of psoriatic skin disease in untreated patients, as represented by PASI.
      Further investigation may add more data on the pathogenetic cascade of psoriasis.

PMID- 25759828
TI  - The secretion of IL-22 from mucosal NKp44+ NK cells is associated with microbial
      translocation and virus infection in SIV/SHIV-infected Chinese macaques.
AB  - Microbial translocation (MT) causes systemic immune activation in chronic human
      immunodeficiency virus (HIV) infection. The role of a novel subtype of innate
      lymphoid cells, the NKp44(+) NK cells, in HIV/simian immunodeficiency virus- (SIV
      ) induced MT remains unknown. In this study, 12 simian-human immunodeficiency
      virus- (SHIV-) infected macaques were chosen and split into two groups based on
      the MT level. Blood and Peripheral lymphoid tissue were sampled for flow
      cytometric analysis, viral load detection, and interleukin testing. Then, six
      naive Chinese macaques were used to determine the dynamics of cytokine secretion
      from mucosal NKp44(+) NK cells in different phases of SIV infection. As a result,
      the degranulation capacity and IL-22 production of mucosal NKp44(+) NK cells were
      associated with the MT level in the SHIV-infected macaques. And the number of
      mucosal NKp44(+) NK cells and IL-22 secretion by these cells were lower in the
      chronic phase than in the early acute phase of SIV infection. The number of
      mucosal NKp44(+) NK cells and interleukin-22 (IL-22) secretion by these cells
      increased before MT occurred. Therefore, we conclude that a decline in IL-22
      production from mucosal NKp44(+) NK cells induced by virus infection may be one
      of the causes of microbial translocation in HIV/SIV infection. 

PMID- 25759830
TI  - Transplanted human umbilical cord mesenchymal stem cells facilitate lesion repair
      in B6.Fas mice.
AB  - BACKGROUND: Systemic lupus erythematosus (SLE) is a multisystem disease that is
      characterized by the appearance of serum autoantibodies. No effective treatment
      for SLE currently exists. METHODS: We used human umbilical cord mesenchymal stem
      cell (H-UC-MSC) transplantation to treat B6.Fas mice. RESULTS: After four rounds
      of cell transplantation, we observed a statistically significant decrease in the
      levels of mouse anti-nuclear, anti-histone, and anti-double-stranded DNA
      antibodies in transplanted mice compared with controls. The percentage of
      CD4(+)CD25(+)Foxp3(+) T cells in mouse peripheral blood significantly increased
      after H-UC-MSC transplantation. CONCLUSIONS: The results showed that H-UC-MSCs
      could repair lesions in B6.Fas mice such that all of the relevant disease
      indicators in B6.Fas mice were restored to the levels observed in normal C57BL/6
      mice.

PMID- 25759831
TI  - Human CD38hiCD138+ plasma cells can be generated in vitro from CD40-activated
      switched-memory B lymphocytes.
AB  - B lymphocyte differentiation into long-lived plasma cells is the keystone event
      for the production of long-term protective antibodies. CD40-CD154 and CD27-CD70
      interactions are involved in human B lymphocyte differentiation into
      CD38(hi)CD138(+) cells in vivo as well as in vitro. In this study, we have
      compared these interactions in their capacity to drive switched-memory B
      lymphocytes differentiation into CD38(hi)CD138(+) plasma cells. The targeted B
      lymphocytes were isolated from human peripheral blood, expanded for 19 days, and
      then submitted to CD70 or CD154 interactions for 14 days. The expanded B
      lymphocytes were constitutively expressing CD39, whereas CD31's expression was
      noticed only following the in vitro differentiation step (day 5) and was
      exclusively present on the CD38(hi) cell population. Furthermore, the generated
      CD38(hi)CD138(+) cells showed a higher proportion of CD31(+) cells than the
      CD38(hi)CD138(-) cells. Besides, analyses done with human blood and bone marrow
      plasma cells showed that in vivo and de novo generated CD38(hi)CD138(+) cells
      have a similar CD31 expression profile but are distinct according to their
      reduced CD39 expression level. Overall, we have evidences that in vitro generated
      plasma cells are heterogeneous and appear as CD39(+) precursors to the ones
      present in bone marrow niches. 

PMID- 25759832
TI  - Immunological effects of environmental factors: focus on the fibrous and
      particulated materials.

PMID- 25759833
TI  - Daily intake of probiotics with high IFN-gamma/IL-10 ratio increases the
      cytotoxicity of human natural killer cells: a personalized probiotic approach.
AB  - A personalized probiotic microfluidic chip system has been established and used
      to screen the probiotics which had the highest value of IFN-gamma/IL-10 or IL
      10/IFN-gamma among six probiotics, including L. paracasei BRAP01, L. acidophilus
      AD300, B. longum BA100, E. faecium BR0085, L. rhamnosus AD500, and L. reuteri
      BR101. One hundred volunteers were included and their PBMCs were collected and
      stimulated by the six probiotics. People who belonged to the IFN-gamma group took
      the probiotics that exerted the highest ratio of IFN-gamma/IL-10 and vice versa
      in IL-10 group. A significant increase in NK cytotoxicity of 69 volunteers in the
      IFN-gamma group was observed compared to the IL-10 group (n = 21) and control
      group (n = 10). The result also showed that L. paracasei BRAP01 and L.
      acidophilus AD300 were the two dominant inducers in IFN-gamma group which yielded
      higher value of IFN-gamma/IL-10 than the other 4 probiotics, while L. reuteri
      BR101 was the most effective agent on the ratio of IL-10/IFN-gamma in the IL-10
      group. Our finding highlighted the concept of personalized probiotics and also
      provided a good foundation to investigate the probiotics with NK activity. 

PMID- 25759834
TI  - Reestablishment of active immunity against HBV graft reinfection after liver
      transplantation for HBV-related end stage liver disease.
AB  - BACKGROUND: The aim of this study was to establish a hepatitis B virus (HBV)
      vaccination protocol among orthotopic liver transplantation (OLT) recipients
      under the coverage of a low-dose hepatitis B immunoglobulin (HBIG) combined with
      an antiviral agent prophylaxis protocol. METHOD: Two hundred OLT recipients were
      included in this study. The vaccine was injected at months 0, 1, 2, and 6. Low
      dose HBIG combined with antiviral agent prophylaxis protocol was continued before
      reestablishment of active immunity against HBV in order to maintain a steady anti
      HBs titer. RESULTS: Active immunity against HBV was reestablished in 50 patients,
      for an overall response rate of 25%. Of the 50 patients, 24 discontinued HBIG
      without any HBV graft reinfection during a follow-up period of 26.13 +/- 7.05
      months. 21 patients discontinued both HBIG and antiviral agents during a follow
      up period of 39.86 +/- 15.47 months, and 4 patients among them appeared to be
      HBsAg positive. There was no recipient death or graft loss because of HBV
      reinfection. CONCLUSIONS: Vaccination preventing HBV reinfection for OLT
      recipients is feasible. The strategy withdrawal of HBIG with induction of active
      immunity against hepatitis B is reasonable for long-term survivors of OLT;
      however, discontinuation nucleoside analogues should be cautious.

PMID- 25759835
TI  - Conventional rapid latex agglutination in estimation of von Willebrand factor:
      method revisited and potential clinical applications.
AB  - Measurement of von Willebrand factor antigen (VWF : Ag) levels is usually
      performed in a specialised laboratory which limits its application in routine
      clinical practice. So far, no commercial rapid test kit is available for VWF : Ag
      estimation. This paper discusses the technical aspect of latex agglutination
      method which was established to suit the purpose of estimating von Willebrand
      factor (VWF) levels in the plasma sample. The latex agglutination test can be
      performed qualitatively and semiquantitatively. Reproducibility, stability,
      linearity, limit of detection, interference, and method comparison studies were
      conducted to evaluate the performance of this test. Semiquantitative latex
      agglutination test was strongly correlated with the reference immunoturbidimetric
      assay (Spearman's rho = 0.946, P < 0.001, n = 132). A substantial agreement
      (kappa = 0.77) was found between qualitative latex agglutination test and the
      reference assay. Using the scoring system for the rapid latex test, no
      agglutination is with 0% VWF : Ag (control negative), 1+ reaction is equivalent
      to <20% VWF : Ag, and 4+ reaction indicates >150% VWF : Ag (when comparing with
      immunoturbidimetric assay). The findings from evaluation studies suggest that
      latex agglutination method is suitable to be used as a rapid test kit for the
      estimation of VWF : Ag levels in various clinical conditions associated with high
      levels and low levels of VWF : Ag.

PMID- 25759836
TI  - Lactic acid bacteria strains exert immunostimulatory effect on H. pylori-induced
      dendritic cells.
AB  - The aim of this study was to find out if selected lactic acid bacteria (LAB)
      strains (antagonistic or nonantagonistic against H. pylori in vitro) would differ
      in their abilities to modulate the DCs maturation profiles reflected by their
      phenotype and cytokine expression patterns. Methods. Monocyte-derived DCs
      maturation was elicited by their direct exposure to the LAB strains of L.
      rhamnosus 900 or L. paracasei 915 (antagonistic and nonantagonistic to H. pylori,
      resp.), in the presence or absence of H. pylori strain cagA+. The DCs maturation
      profile was assessed on the basis of surface markers expression and cytokines
      production. Results. We observed that the LAB strains and the mixtures of LAB
      with H. pylori are able to induce mature DCs. At the same time, the L. paracasei
      915 leads to high IL-10/IL-12p70 cytokine ratio, in contrast to L. rhamnosus 900.
      Conclusions. This study showed that the analyzed lactobacilli strains are more
      potent stimulators of DC maturation than H. pylori. Interestingly from the two
      chosen LAB strains the antagonistic to H. pylori-L. rhamnosus strain 900 has more
      proinflammatory and probably antibactericidal properties. 

PMID- 25759837
TI  - Characterization of Toll-like receptor-4 (TLR-4) in the spleen and thymus of
      Swiss albino mice and its modulation in experimental endotoxemia.
AB  - Expression of innate immune receptors varies among organs and species and within
      different strains among the same species; thus, periodic classification of
      different pattern recognition receptors in the available strains is necessary to
      initiate different therapeutic approaches to combat inflammation. On
      characterization of TLR-4 in spleen and thymus of Swiss albino mice--with no
      reports of TLR-4 expression--induced with endotoxemia, it was found that the mode
      of expression varied among the organs at both mRNA and protein level in a time
      dependent manner. Their functionality was verified by measuring proinflammatory
      and anti-inflammatory cytokines. In the in vitro study using isolated macrophages
      and lymphocytes from the same organs, the expression of TLR-4 after a shorter
      period of LPS stimulation was verified. The results substantiated the potent role
      of macrophage on LPS challenge compared to lymphocytes. The diverse pattern of
      TLR-4 expression on different cell population indicated their distinct functional
      activity in LPS-endotoxemia. It may be hypothesized that the expression patterns
      of TLR-4 could be different based on the anatomical localization and the varying
      bacterial milieu or bacterial endotoxin encountered in each anatomical location.
      Thus, blocking TLR-4 or administering IL-6 or IL-10 might impart protection
      against endotoxemia in the clinical field.

PMID- 25759838
TI  - Prolonged helium postconditioning protocols during early reperfusion do not
      induce cardioprotection in the rat heart in vivo: role of inflammatory cytokines.
AB  - Postconditioning of myocardial tissue employs short cycles of ischemia or
      pharmacologic agents during early reperfusion. Effects of helium postconditioning
      protocols on infarct size and the ischemia/reperfusion-induced immune response
      were investigated by measurement of protein and mRNA levels of proinflammatory
      cytokines. Rats were anesthetized with S-ketamine (150 mg/kg) and diazepam (1.5
      mg/kg). Regional myocardial ischemia/reperfusion was induced; additional groups
      inhaled 15, 30, or 60 min of 70% helium during reperfusion. Fifteen minutes of
      helium reduced infarct size from 43% in control to 21%, whereas 30 and 60 minutes
      of helium inhalation led to an infarct size of 47% and 39%, respectively.
      Increased protein levels of cytokine-induced neutrophil chemoattractant (CINC-3)
      and interleukin-1 beta (IL-1beta) were found after 30 or 60 min of helium
      inhalation, in comparison to control. 30 min of helium increased mRNA levels of
      CINC-3, IL-1beta, interleukin 6 (IL-6), and tumor necrosis factor alpha (TNF
      alpha) in myocardial tissue not directly subjected to ischemia/reperfusion. These
      results suggest that the effectiveness of the helium postconditioning protocol is
      very sensitive to duration of noble gas application. Additionally, helium was
      associated with higher levels of inflammatory cytokines; however, it is not clear
      whether this is causative of nature or part of an epiphenomenon. 

PMID- 25759840
TI  - Evidence for contribution of CD4+ CD25+ regulatory T cells in maintaining immune
      tolerance to human factor IX following perinatal adenovirus vector delivery.
AB  - Following fetal or neonatal gene transfer in mice and other species immune
      tolerance of the transgenic protein is frequently observed; however the
      underlying mechanisms remain largely undefined. In this study fetal and neonatal
      BALB/c mice received adenovirus vector to deliver human factor IX (hFIX) cDNA.
      The long-term tolerance of hFIX was robust in the face of immune challenge with
      hFIX protein and adjuvant but was eliminated by simultaneous administration of
      anti-CD25+ antibody. Naive irradiated BALB/c mice which had received lymphocytes
      from donors immunised with hFIX developed anti-hFIX antibodies upon immune
      challenge. Cotransplantation with CD4+CD25+ cells isolated from neonatally
      tolerized donors decreased the antibody response. In contrast, cotransplantation
      with CD4+CD25- cells isolated from the same donors increased the antibody
      response. These data provide evidence that immune tolerance following perinatal
      gene transfer is maintained by a CD4+CD25+ regulatory population. 

PMID- 25759839
TI  - The multifaceted role of commensal microbiota in homeostasis and gastrointestinal
      diseases.
AB  - The gastrointestinal tract houses a complex and diverse community of microbes. In
      recent years, an increased understanding of the importance of intestinal
      microbiota for human physiology has been gained. In the steady state, commensal
      microorganisms have a symbiotic relationship with the host and possess critical
      and distinct functions, including directly influencing immunity. This means that
      recognition of commensal antigens is necessary for the development of complete
      immune responses. Therefore, the immune system must face the challenge of
      maintaining mucosal homeostasis while dealing with undue passage of commensal or
      pathogenic microbes, as well as the host nutritional status or drug use.
      Disruption of this fine balance has been associated with the development of
      several intestinal inflammatory diseases. In this review, we discuss the
      mechanisms involved in the modulation of host-microbe interactions and how the
      breakdown of this homeostatic association can lead to intestinal inflammation and
      pathology. 

PMID- 25759841
TI  - Cloning of interleukin-10 from African clawed frog (Xenopus tropicalis), with the
      Finding of IL-19/20 homologue in the IL-10 locus.
AB  - Interleukin-10 (IL-10) is a pleiotropic cytokine that plays an important role in
      immune system. In the present study, the IL-10 gene of African clawed frog
      (Xenopus tropicalis) was first cloned, and its expression pattern and 3D
      structure were also analyzed. The frog IL-10 mRNA encoded 172 amino acids which
      possessed several conserved features found in IL-10s from other species,
      including five-exon/four-intron genomic structure, conserved four cysteine
      residues, IL-10 family motif, and six alpha-helices. Real-time PCR showed that
      frog IL-10 mRNA was ubiquitous expressed in all examined tissues, highly in some
      immune related tissues including kidney, spleen, and intestine and lowly in
      heart, stomach, and liver. The frog IL-10 mRNA was upregulated at 24 h after LPS
      stimulation, indicating that it plays a part in the host immune response to
      bacterial infection. Another IL, termed as IL-20, was identified from the frog IL
      10 locus, which might be the homologue of mammalian IL-19/20 according to the
      analysis results of the phylogenetic tree and the sequence identities. 

PMID- 25759842
TI  - CD69 is the crucial regulator of intestinal inflammation: a new target molecule
      for IBD treatment?
AB  - CD69 has been identified as an early activation marker of lymphocytes. However,
      recent work has indicated that CD69 plays an essential role for the regulation of
      inflammatory processes. Particularly, CD69 is highly expressed by lymphocytes at
      mucosal sites being constantly exposed to the intestinal microflora (one of the
      nature's most complex and most densely populated microbial habitats) and food
      antigens, while only a small number of circulating leukocytes express this
      molecule. In this review we will discuss the role of CD69 in mucosal tissue and
      consider CD69 as a potential target for the development of novel treatments of
      intestinal inflammation. 

PMID- 25759843
TI  - Administration of Bifidobacterium breve PS12929 and Lactobacillus salivarius
      PS12934, two strains isolated from human milk, to very low and extremely low
      birth weight preterm infants: a pilot study.
AB  - The preterm infant gut has been described as immature and colonized by an
      aberrant microbiota. Therefore, the use of probiotics is an attractive practice
      in hospitals to try to reduce morbidity and mortality in this population. The
      objective of this pilot study was to elucidate if administration of two probiotic
      strains isolated from human milk to preterm infants led to their presence in
      feces. In addition, the evolution of a wide spectrum of immunological compounds,
      including the inflammatory biomarker calprotectin, in both blood and fecal
      samples was also assessed. For this purpose, five preterm infants received two
      daily doses (~10(9) CFU) of a 1:1 mixture of Bifidobacterium breve PS12929 and
      Lactobacillus salivarius PS12934. Bacterial growth was detected by culture
      dependent techniques in all the fecal samples. The phylum Firmicutes dominated in
      nearly all fecal samples while L. salivarius PS12934 was detected in all the
      infants at numerous sample collection points and B. breve PS12929 appeared in
      five fecal samples. Finally, a noticeable decrease in the fecal calprotectin
      levels was observed along time.

PMID- 25759844
TI  - HIV and the gut microbiota, partners in crime: breaking the vicious cycle to
      unearth new therapeutic targets.
AB  - The gut microbiota plays a key role in health and immune system education and
      surveillance. The delicate balance between microbial growth and containment is
      controlled by the immune system. However, this balance is disrupted in cases of
      chronic viral infections such as HIV. This virus is capable of drastically
      altering the immune system and gastrointestinal environment leading to
      significant changes to the gut microbiota and mucosal permeability resulting in
      microbial translocation from the gut into the peripheral blood. The changes made
      locally in the gut have far-reaching consequences on the other organs of the body
      starting in the liver, where microbes and their products are normally filtered
      out, and extending to the blood and even brain. Microbial translocation and their
      downstream effects such as increased indolamine 2,3-dioxygenase (IDO) enzyme
      expression and activity create a self-sustaining feedback loop which enhances HIV
      disease progression and constitute a vicious cycle of inflammation and immune
      activation combining viral and bacterial factors. Understanding this self
      perpetuating cycle could be a key element in developing new therapies aimed at
      the gut microbiota and its fallout after infection. 

PMID- 25759846
TI  - TRAIL modulates the immune system and protects against the development of
      diabetes.
AB  - TRAIL or tumor necrosis factor (TNF) related apoptosis-inducing ligand is a
      member of the TNF superfamily of proteins, whose best characterized function is
      the induction of apoptosis in tumor, infected, or transformed cells through
      activation of specific receptors. In nontransformed cells, however, the actions
      of TRAIL are less well characterized. Recent studies suggest that TRAIL may be
      implicated in the development and progression of diabetes. Here we review TRAIL
      biological actions, its effects on the immune system, and how and to what extent
      it has been shown to protect against diabetes. 

PMID- 25759847
TI  - Fas ligand DNA enhances a vaccination effect by coadministered DNA encoding a
      tumor antigen through augmenting production of antibody against the tumor
      antigen.
AB  - Interaction of Fas and Fas ligand (FasL) plays an important role in the
      regulation of immune responses by inducing apoptosis of activated cells; however,
      a possible role of FasL in DNA vaccination has not been well understood. We
      examined whether administration of DNA encoding FasL gene enhanced antitumor
      effects in mice that were vaccinated with DNA expressing a putative tumor antigen
      gene, beta-galactosidase (beta-gal). Growth of beta-gal-positive Colon 26 tumors
      was retarded in the syngeneic mice immunized with beta-gal and FasL DNA compared
      with those vaccinated with beta-gal or FasL DNA. We did not detect increased
      numbers of beta-gal-specific CD8(+) T cells in lymph node of mice that received
      combination of beta-gal and FasL DNA, but amounts of anti-beta-gal antibody
      increased with the combination but not with beta-gal or FasL DNA injection alone.
      Subtype analysis of anti-beta-gal antibody produced by the combination of beta
      gal and FasL DNA or beta-gal DNA injection showed that IgG2a amounts were greater
      in mice injected with both DNA than those with beta-gal DNA alone, but IgG2b
      amounts were lower in both DNA-injected than beta-gal DNA-injected mice. These
      data suggest that FasL is involved in boosting humoral immunity against a gene
      product encoded by coinjected DNA and enhances the vaccination effects. 

PMID- 25759848
TI  - Statins increase the frequency of circulating CD4+ FOXP3+ regulatory T cells in
      healthy individuals.
AB  - Statins have been shown to modulate the number and the suppressive function of
      CD4(+)FOXP3(+) T cells (Treg) in inflammatory conditions. However, it is not well
      established whether statin could also affect Treg in absence of inflammation. To
      address this question, eighteen normocholesterolemic male subjects were treated
      with lovastatin or atorvastatin daily for 45 days. The frequency and phenotype of
      circulating Treg were evaluated at days 0, 7, 30, and 45. mRNA levels of FOXP3,
      IDO, TGF-beta, and IL-10 were measured in CD4(+) T cells. We found that both
      statins significantly increased Treg frequency and FOXP3 mRNA levels at day 30.
      At day 45, Treg numbers returned to baseline values; however, TGF-beta and FOXP3
      mRNA levels remained high, accompanied by increased percentages of CTLA-4- and
      GITR-expressing Treg. Treg Ki-67 expression was decreased upon statin treatment.
      Treg frequency positively correlated with plasma levels of high-density
      lipoprotein cholesterol (HDL-c), suggesting a role for HDL-c in Treg homeostasis.
      Therefore, statins appear to have inflammation-independent immune-modulatory
      effects. Thus, the increase in Treg cells frequency likely contributes to
      immunomodulatory effect of statins, even in healthy individuals. 

PMID- 25759849
TI  - Clinical comparison of QUANTA Flash dsDNA chemiluminescent immunoassay with four
      current assays for the detection of anti-dsDNA autoantibodies.
AB  - INTRODUCTION: The objective of the present study was to compare QUANTA Flash
      dsDNA, a chemiluminescent immunoassay (CIA) on the BIO-FLASH, a rapid-response
      chemiluminescent analyzer, to three other anti-dsDNA antibody assays and to
      Crithidia luciliae indirect immunofluorescence test (CLIFT). METHODS: In the
      first part of the study, 161 samples, 61 from patients suffering from systemic
      lupus erythematosus (SLE) and 100 from a disease control group, were tested by
      QUANTA Flash dsDNA CIA, QUANTA Lite dsDNA SC ELISA, BioPlex 2200 multiplex flow
      immunoassay (MFI), ImmuLisa dsDNA ELISA, and NOVA Lite CLIFT. A second cohort of
      69 SLE patients was then tested by QUANTA Flash dsDNA and CLIFT to expand the
      study. RESULTS: The overall qualitative agreements varied between 77.0% (NOVA
      Lite CLIFT versus QUANTA Lite) and 89.4% (ImmuLisa versus NOVA Lite CLIFT). The
      clinical sensitivities for the anti-dsDNA antibody tests varied from 8.2% (NOVA
      Lite CLIFT) to 54.1% (QUANTA Lite), while the clinical specificities varied from
      88.0% (BioPlex 2200) to 100.0% (NOVA Lite CLIFT). Good correlation was found
      between QUANTA Flash dsDNA and NOVA Lite CLIFT. CONCLUSION: Significant
      variations among dsDNA methods were observed. QUANTA Flash dsDNA provides a good
      combination of sensitivity and specificity for the diagnosis of SLE and good
      agreement to CLIFT.

PMID- 25759845
TI  - Insights into the antiviral immunity against grass carp (Ctenopharyngodon idella)
      reovirus (GCRV) in grass carp.
AB  - Global fish production from aquaculture has rapidly grown over the past decades,
      and grass carp shares the largest portion. However, hemorrhagic disease caused by
      grass carp reovirus (GCRV) results in tremendous loss of grass carp
      (Ctenopharyngodon idella) industry. During the past years, development of
      molecular biology and cellular biology technologies has promoted significant
      advances in the understanding of the pathogen and the immune system.
      Immunoprophylaxis based on stimulation of the immune system of fish has also got
      some achievements. In this review, authors summarize the recent progresses in
      basic researches on GCRV; viral nucleic acid sensors, high-mobility group box
      proteins (HMGBs); pattern recognition receptors (PRRs), Toll-like receptors
      (TLRs) and retinoic acid inducible gene I- (RIG-I-) like receptors (RLRs);
      antiviral immune responses induced by PRRs-mediated signaling cascades of type I
      interferon (IFN-I) and IFN-stimulated genes (ISGs) activation. The present review
      also notices the potential applications of molecule genetic markers.
      Additionally, authors discuss the current preventive and therapeutic strategies
      (vaccines, RNAi, and prevention medicine) and highlight the importance of innate
      immunity in long term control for grass carp hemorrhagic disease. 

PMID- 25759851
TI  - Rapid Prototyping Technologies and their Applications in Prosthodontics, a Review
      of Literature.
AB  - The early computer-aided design/computer-aided manufacturing (CAD/CAM) systems
      were relied exclusively on subtractive methods. In recent years, additive methods
      by employing rapid prototyping (RP) have progressed rapidly in various fields of
      dentistry as they have the potential to overcome known drawbacks of subtractive
      techniques such as fit problems. RP techniques have been exploited to build
      complex 3D models in medicine since the 1990s. RP has recently proposed
      successful applications in various dental fields, such as fabrication of implant
      surgical guides, frameworks for fixed and removable partial dentures, wax
      patterns for the dental prosthesis, zirconia prosthesis and molds for metal
      castings, and maxillofacial prosthesis and finally, complete dentures. This paper
      aimed to offer a comprehensive literature review of various RP methods,
      particularly in dentistry, that are expected to bring many improvements to the
      field. A search was made through MEDLINE database and Google scholar search
      engine. The keywords; 'rapid prototyping' and 'dentistry' were searched in
      title/abstract of publications; limited to 2003 to 2013, concerning past decade.
      The inclusion criterion was the technical researches that predominately included
      laboratory procedures. The exclusion criterion was meticulous clinical and
      excessive technical procedures. A total of 106 articles were retrieved, recited
      by authors and only 50 met the specified inclusion criteria for this review.
      Selected articles had used rapid prototyping techniques in various fields in
      dentistry through different techniques. This review depicted the different
      laboratory procedures employed in this method and confirmed that RP technique
      have been substantially feasible in dentistry. With advancement in various RP
      systems, it is possible to benefit from this technique in different dental
      practices, particularly in implementing dental prostheses for different
      applications. 

PMID- 25759852
TI  - The Effect of Temperature on Shear Bond Strength of Clearfil SE Bond and Adper
      Single Bond Adhesive Systems to Dentin.
AB  - STATEMENT OF THE PROBLEM: Monomer viscosity and solvent evaporation can be
      affected by the adhesive system temperature. Higher temperature can elevate the
      vapor pressure in solution and penetration of adhesive in smear layer. Bonding
      mechanism may be influenced by the adhesive temperature. PURPOSE: This study
      aimed to evaluate the effect of pre-heating on shear bond strength of etch-and
      rinse and self-etching adhesives to ground bovine dentin surfaces, at
      temperatures of 4C, 25C and 40C. MATERIALS AND METHOD: In this experimental
      study, 60 maxillary bovine incisors were randomly divided into 6 groups (n=10).
      The central part of labial dentin surfaces was exposed with a diamond bur and
      standardized smear layer was created by using silicon carbide paper (600 grit)
      under water-coolant while the specimens were mounted in acrylic resin. Two
      adhesive systems, an etch-and-rinse (Adper single bond) and a self-etch (Clearfil
      SE Bond) were stored at temperatures of 4C, 25C and 40C for 30 minutes and were
      then applied on the prepared labial surface according to the manufacturer's
      instructions. The composite resin (Z350) was packed in Teflon mold (5 mm in
      diameter) on this surface and was cured. The shear bond strength (MPa) was
      evaluated by universal testing machine (Zwick/Roell Z020, Germany) at cross head
      speed of 1mm/min. The results were statistically analyzed by using ANOVA and
      Tukey tests (p< 0.05). RESULTS: No significant difference was found between the
      shear bond strength of Clearfil SE Bond adhesive in different temperature and
      single Bond adhesive system at 25 C and 40 C. However, there were significant
      differences between 4 C of Adper single bond in comparison with 25C and 40C (p=
      0.0001). CONCLUSION: Pre-heating did not affect the shear bond strength of SE
      Bond, but could promote the shear bond strength of Adper Single Bond.

PMID- 25759853
TI  - Head and neck metastatic tumors: a retrospective survey of Iranian patients.
AB  - STATEMENT OF THE PROBLEM: The head and neck region is an uncommon site for
      metastatic involvement, but it can be the first and only symptom of primary
      cancer. The incidence of these tumors and their primary origins are limited in
      Iranian patients. PURPOSE: Therefore, this retrospective study aimed to
      investigate the frequency and the common related clinical manifestations, as well
      as, the most common types of cancers and the prevalent sites of the primary
      tumor. MATERIALS AND METHOD: All medical records related to patients with history
      of head and neck tumors between 1991 and 2011 at Iran Cancer Institute were
      evaluated and the essential information was statistically analyzed. RESULTS:
      Sixty cases of cervical lymph node metastasis (0.36%) and 26 cases of head and
      neck metastatic tumors (0.16%) including 17 cases of distant cancer (0.10%) were
      recorded among all 16232 registered cancers. Out of all distant head and neck
      metastatic tumors, 4 cases were related to oral and maxillofacial area. Pain,
      swelling of neck, oral mucosa ulcer and dryness were the chief complaints.
      Squamous cell carcinoma and adenocarcinoma were the most frequent types of
      cancers. The most common metastatic sites were cervical musculature, scalp and
      parotid gland, and the most prevalent sites of primary tumor in females were
      breast and lung in males. CONCLUSION: According to these cases, the incidence
      rate of head and neck metastatic tumors seems to be low. However, feasible
      similarity of clinical presentation of oral metastatic lesions to benign lesions
      might result in misdiagnosis. Hence, biopsy is mandatory in any case with unusual
      clinical presentation, especially in patients with a known malignant disease.

PMID- 25759854
TI  - Evaluating the Stability of Open Bite Treatments and Its Predictive Factors in
      the Retention Phase during Permanent Dentition.
AB  - STATEMENT OF THE PROBLEM: Orthodontists often find challenges in treating the
      anterior open bite and maintaining the results. PURPOSE: This retrospective study
      was aimed to evaluate the stability of corrected open bite in the retention phase
      during permanent dentition. MATERIALS AND METHOD: A total number of 37 patients,
      including 20 males and 17 females, with the mean age of 18+/-2.1 years at the
      beginning of the treatment were studied after correction of the anterior open
      bite. Overbites of the patients were measured from their lateral cephalograms
      before (T1), at the end (T2) and at least 3 years after the end of the treatment
      in the presence of their fixed retainers (T3).The mean overbite changes and the
      number of patients with open bite, due to treatment relapse, at T3 were
      calculated. The relationship between the pre-treatment factors and the treatment
      relapse was assessed at T1 and T2. Also the effects of treatment methods,
      extraction and adjunctive use of removable appliances on the post-treatment
      relapse were evaluated. RESULTS: The mean overbite change during the post
      treatment period was -0.46+/-0.7 mm and six patients (16.2%) had relapse in the
      follow-up recall. Cephalometric Jaraback index showed statistically significant,
      but weak correlation with overbite changes after the treatment (p= 0.035; r= 
      0.353). No significant difference was found between the extraction and non
      extraction groups (p= 0.117) the use and the type of the removable appliances (p=
      0.801). CONCLUSION: Fixed retainers alone are insufficient for stabilizing the
      results of corrected open bite. The change of overbite in the retention phase
      could not be predicted from cephalometric measurements. Extraction and use of
      adjunctive removable appliance did not have any effect on the treatment relapse.

PMID- 25759850
TI  - Intestinal microbiota as modulators of the immune system and neuroimmune system:
      impact on the host health and homeostasis.
AB  - Many immune-based intestinal disorders, such as ulcerative colitis and Crohn's
      disease, as well as other illnesses, may have the intestines as an initial cause
      or aggravator in the development of diseases, even apparently not correlating
      directly to the intestine. Diabetes, obesity, multiple sclerosis, depression, and
      anxiety are examples of other illnesses discussed in the literature. In parallel,
      importance of the gut microbiota in intestinal homeostasis and immunologic
      conflict between tolerance towards commensal microorganisms and combat of
      pathogens is well known. Recent researches show that the immune system, when
      altered by the gut microbiota, influences the state in which these diseases are
      presented in the patient directly and indirectly. At the present moment, a
      considerable number of investigations about this subject have been performed and
      published. However, due to difficulties on correlating information, several
      speculations and hypotheses are generated. Thus, the present review aims at
      bringing together how these interactions work-gut microbiota, immune system, and
      their influence in the neuroimmune system. 

PMID- 25759855
TI  - Influence of Different Power Outputs of Er:YAG Laser on Shear Bond Strength of a
      Resin Composite to Feldspathic Porcelain.
AB  - STATEMENT OF THE PROBLEM: Porcelain may fracture or chip if exposed to any
      traumas and can be repaired by using a resin composite. PURPOSE: This study was
      aimed to evaluate the influences of Er:YAG laser on shear bond strength (SBS) of
      resin composite to feldspathic porcelain. MATERIALS AND METHOD: Seventy-two
      porcelain blocks were divided into six groups (n=12): G1: no treatment (control
      group); G2: 9% hydrofluoric acid (HF); G3-6 were separately irradiated with
      Er:YAG laser using four energy parameters: 2W, 100mj (G3); 3W, 150mj (G4); 4W,
      200mj (G5) and 5W, 250mj (G6), respectively; and 20 Hz frequency in long-pulse
      mode. After silane treatment, a resin composite rod was bonded to each of the
      porcelain block. The SBS was measured following storage and thermocycling. Data
      were analyzed by one-way ANOVA, Tamhane and Chi-Square tests. RESULTS: The
      highest SBS (12.29+/-3.04 MPa) was obtained with HF (G2). The lowest SBS (2.23+/
      0.60 MPa) was observed in G4, followed by G3 (1.96+/-0.76 MPa). G6 had a
      significantly higher SBS (8.00+/-2.22 MPa) than other laser irradiation groups.
      CONCLUSION: Although, Er:YAG laser irradiation at 5W, 250mJ/20 Hz was effective
      in promoting adhesion of resin composite to feldspathic porcelain compared with
      the control group, it cannot be used as a safe alternative method to HF acid.
      Laser irradiation with the evaluated parameters in this study does not promote an
      effective adhesion on porcelain surface to create adequate bond for clinical use.

PMID- 25759856
TI  - The effect of blood contamination on the compressive strength of calcium-enriched
      mixture.
AB  - STATEMENT OF THE PROBLEM: In clinical situations, Calcium-Enriched Mixture (CEM)
      comes into direct contact or even mixes with blood during or after placement.
      PURPOSE: The aim of this study was to evaluate the effect of blood contamination
      on the compressive strength of CEM. MATERIALS AND METHOD: Three experimental
      groups were included in this study. In the first group, CEM was mixed with
      distilled water and was exposed to normal saline (control group). In the second
      group, CEM cement was mixed with distilled water and then was exposed to blood.
      In the third group, CEM was mixed with and exposed to blood. Nine custom-made two
      part split Plexiglas molds with five holes were used to form CEM samples for
      compressive strength testing (15 samples in each group). After 7 days of
      incubation, compressive bond strength testing was performed using a universal
      testing machine. Data were statistically analyzed using the Mann-Whitney U test
      with a significance level of p< 0.05. RESULTS: Nine samples from group 3 were
      fractured during removal from the molds; the other six blocks had some cracks on
      their surfaces. Therefore, a compressive strength measurement was not obtainable
      for this group. No statistically significant difference was found between groups
      1 and 2 (p> 0.05). CONCLUSION: It can be concluded that exposure to blood does
      not adversely affect the compressive strength of CEM, but incorporation of blood
      makes the cement very brittle.

PMID- 25759857
TI  - Anatomical Variations of Ostiomeatal Complex in CBCT of Patients Seeking
      Rhinoplasty.
AB  - STATEMENT OF THE PROBLEM: Anatomic variation can potentially impact the surgical
      safety. PURPOSE: The purpose of this cross-sectional study was to assess the
      prevalence of ostiomeatal complex variations based on cone beam computed
      tomography (CBCT) images of the patients seeking rhinoplasty. MATERIALS AND
      METHOD: In this cross-sectional study, CBCT images of 281 patients including 153
      female and 128 male with Mean+/-SD age of 26.97+/-7.38 were retrieved and
      analyzed for presence of variations of ostiomeatal complex and mucosal
      thickening. All CBCT images were acquired by NewTom VGi scanner with 15*15 field
      of view, as a part of preoperative recording of patients seeking rhinoplasty in
      an otolaryngology clinic. Chi- square test and Odds ratio were used for
      statistical analysis of the obtained data and p< 0.05 was considered to be
      statistically significant. RESULTS: Agger nasi cells which were seen in 93.2% of
      the cases were the most common anatomic variation. It was followed by Haller
      cells (68%), concha bullosa (67.3%), uncinate process variations (54.8%), nasal
      sepal deviation (49.5%) and paradoxical curvature of middle turbinate (10%).
      Mucosal thickening were detected in 60.7% of the studied cases. CONCLUSION:
      Ostiomeatal complex variations and mucosal thickening are considerably prevalent
      among the patients seeking rhinoplasty. This study also revealed that CBCT
      evaluation of paranasal sinuses has comparable result in delineation of the
      sinonasal anatomy.

PMID- 25759858
TI  - Comparing the Effects of Whey Extract and Casein Phosphopeptide-Amorphous Calcium
      Phosphate (CPP-ACP) on Enamel Microhardness.
AB  - STATEMENT OF THE PROBLEM: With the recent focus of researches on the development
      of non-invasive treatment modalities, the non-invasive treatment of early carious
      lesions by remineralization would bring a major advance in the clinical
      management of these dental defects. Casein phosphopeptide-amorphous calcium
      phosphate (CPP-ACP) is considered to be effective in tooth remineralization.
      PURPOSE: The aim of this in-vitro study was to compare the effects of whey and
      CPP-ACP in increasing the enamel microhardness. MATERIALS AND METHOD:
      Microhardness of 30 sound human permanent premolars was measured before and after
      8-minute immersion of samples in Coca-Cola. The teeth were then randomly divided
      into 3 groups and were immersed in artificial saliva, whey, and tooth mousse for
      10 minutes. The changes of microhardness within each group and among the groups
      were recorded and analyzed using paired t-test. RESULTS: The microhardness
      increased in each group and between the groups; this increase was statistically
      significant (p= 0.009). CONCLUSION: The effect of whey on increasing the enamel
      microhardness was more than that of tooth mousse.

PMID- 25759859
TI  - The Effects of Chlorhexidine and Persica Mouthwashes on Colonization of
      Streptococcus mutans on Fixed Orthodontics O-rings.
AB  - STATEMENT OF THE PROBLEM: Fixed orthodontic appliances predispose patients to
      dental caries. Use of mouthrinses has been introduced as the effective way for
      reducing dental plaque accumulation. PURPOSE: The aim of this study was to
      compare the effects of Persica mouthwash and Chlorhexidine (CHX) on colonization
      of Streptococcus mutans (S. mutans) on fixed orthodontic O-rings. MATERIALS AND
      METHOD: Thirty patients with fixed orthodontic appliances and proper oral hygiene
      were randomly provided by CHX and Persica and trained to use these mouthwashes
      according to the manufacturer's instruction. Sampling was carried out right
      before and 4 weeks after mouthrinsing treatment. The mean amounts of S. mutans
      colonies in these groups were compared. RESULTS: Comparison of S. mutans
      colonization within each group revealed both mouthrinses to be efficient.
      However, this difference was found to be significant only in CHX group.
      CONCLUSION: Persica cannot be a good alternative mouthwash and patients on
      orthodontic treatment are still recommended to use CHX.

PMID- 25759860
TI  - A novel single-stage procedure for increasing the width of attached gingiva and
      eliminating the aberrant frenal attachment.
AB  - Common treatment for buccal gingival recession caused by an aberrant frenal
      attachment includes elimination of the frenum and treatment of the gingival
      recession by soft tissue graft to increase the width of the attached gingiva that
      in turn results in root coverage. Keratinised gingival, if present in adequate
      amount, maintains the gingival health by protecting the marginal gingiva. This
      not only considers the desires of the patient but also explores the potential
      regenerative capacity of the tissues. This report describes a novel single-stage
      procedure for increasing the width of the attached gingiva and eliminating the
      aberrant frenal attachment. 

PMID- 25759861
TI  - Availability improvement of layer 2 seamless networks using OpenFlow.
AB  - The network robustness and reliability are strongly influenced by the
      implementation of redundancy and its ability of reacting to changes. In
      situations where packet loss or maximum latency requirements are critical,
      replication of resources and information may become the optimal technique. To
      this end, the IEC 62439-3 Parallel Redundancy Protocol (PRP) provides seamless
      recovery in layer 2 networks by delegating the redundancy management to the end
      nodes. In this paper, we present a combination of the Software-Defined Networking
      (SDN) approach and PRP topologies to establish a higher level of redundancy and
      thereby, through several active paths provisioned via the OpenFlow protocol, the
      global reliability is increased, as well as data flows are managed efficiently.
      Hence, the experiments with multiple failure scenarios, which have been run over
      the Mininet network emulator, show the improvement in the availability and
      responsiveness over other traditional technologies based on a single active path.

PMID- 25759863
TI  - Ensemble classifier for epileptic seizure detection for imperfect EEG data.
AB  - Brain status information is captured by physiological electroencephalogram (EEG)
      signals, which are extensively used to study different brain activities. This
      study investigates the use of a new ensemble classifier to detect an epileptic
      seizure from compressed and noisy EEG signals. This noise-aware signal
      combination (NSC) ensemble classifier combines four classification models based
      on their individual performance. The main objective of the proposed classifier is
      to enhance the classification accuracy in the presence of noisy and incomplete
      information while preserving a reasonable amount of complexity. The experimental
      results show the effectiveness of the NSC technique, which yields higher
      accuracies of 90% for noiseless data compared with 85%, 85.9%, and 89.5% in other
      experiments. The accuracy for the proposed method is 80% when SNR=1 dB, 84% when
      SNR=5 dB, and 88% when SNR=10 dB, while the compression ratio (CR) is 85.35% for
      all of the datasets mentioned.

PMID- 25759864
TI  - Tailoring the optical properties of lanthanide phosphors: prediction and
      characterization of the luminescence of Pr(3+)-doped LiYF4.
AB  - We present a theoretical work detailing the electronic structure and the optical
      properties of (PrF8)(5-) embedded in LiYF4, complementing the insight with data
      that are not available by experimental line. The local distortions due to the
      embedding of the lanthanide ion in the sites occupied in the periodic lattice by
      smaller yttrium centres, not detectable in regular X-ray analyses, are reproduced
      with the help of geometry optimization. Then, based on the local coordination
      environment, the relation structure-optical properties is constructed by Density
      Functional Theory computations in conjunction with the ligand field theory
      analyses (LFDFT) determining the [Xe]4f(2)-> [Xe]4f(1)5d(1) transitions. In
      previous instances we analysed rather symmetric systems, here facing the
      complexity of low symmetry cases, treated in the Wybourne ligand field
      parameterization and in the Angular Overlap Model (AOM) frame. A very important
      improvement at the AOM level is the consideration of the f-d mixing that brings
      coupling term of odd-even nature, essential for the realistic description of the
      asymmetric coordination centres. Furthermore, we introduce now a principle for
      modelling the emission intensity. The results are in agreement with available
      experimental findings. The relevance of the modelling has a practical face in the
      rational design of optimal luminescent materials needed in domestic lightening
      and also an academic side, revisiting with modern computational tools areas
      incompletely explored by the standard ligand field theories. 

PMID- 25759862
TI  - Methodological issues on planning and running the Brazilian Multicenter Study on
      Preterm Birth.
AB  - OBJECTIVES: Assuming that the occurrence of preterm births and their maternal and
      neonatal associated conditions in Brazil are not completely known, a multicenter
      study was proposed. The purpose of this paper is to describe the methods used,
      its processes, achievements, and challenges. STUDY DESIGN: A multicenter cross
      sectional study on preterm births in Brazilian facilities plus a nested case
      control study to assess their associated factors. A description of all steps of
      planning and implementing such a nationwide study, including strategies for
      dealing with problems arising during the process, is presented. RESULTS: 20
      referral hospitals in different regions of Brazil participated in the study. A
      detailed questionnaire for data collection, an electronic platform for data
      transcription and monitoring, research materials, and specific monitoring tools
      were developed; then data management and analyses were performed. Finally, we got
      information on 4,150 preterm births and 1,146 term births. CONCLUSIONS: This
      study represented the first step of a planned comprehensive assessment of preterm
      birth in Brazil, with detailed information that will lead to several analyses and
      further studies, bringing the knowledge to improve screening, diagnosis, and
      treatment practices in maternal and perinatal health with the final purpose of
      reducing the burden of this condition in the country.

PMID- 25759865
TI  - Deprotonation of a dinuclear copper complex of 3,5-diamino-1,2,4-triazole for
      high oxygen reduction activity.
AB  - A dinuclear copper(II) complex of 3,5-diamino-1,2,4-triazole is one of the highly
      active copper-based catalysts for the oxygen reduction reaction (ORR) in basic
      solutions. Our in situ X-ray absorption near edge structure measurements revealed
      that deprotonation of the triazole ligand might cause coordination geometrical
      changes, resulting in the enhancement of the ORR activity.

PMID- 25759866
TI  - Insights into the reaction mechanism of CO oxidative coupling to dimethyl oxalate
      over palladium: a combined DFT and IR study.
AB  - Oxidative coupling of toxic pollutant CO to form the platform raw chemical
      material dimethyl oxalate (DMO) has been industrialized however the catalytic
      mechanism has been unknown so far. The reaction mechanism of CO oxidative
      coupling to form DMO on a Pd(111) surface has been investigated using density
      functional theory (DFT) and in situ diffuse reflectance infrared (DRIR)
      spectroscopy. DFT calculations and in situ DRIRS measurements indicate that two
      co-adsorbed intermediates COOMe and OCCO, initiate the reaction. C-C coupling
      occurs earlier due to a low coupling barrier and small steric hindrance. The
      results also suggest that Pd(111) is selective towards DMO over DMC, and that CO
      pre-adsorption and CO in excess effectively enhance the yield of DMO. The
      microscopic elucidation of this important reaction suggests improvements in coal
      to-EG (CTEG) production which can be applied in practice to effectively enhance
      the yield and reduce the cost. The results may help with further fine-tuning and
      designing of high-efficient noble metal catalysts. 

PMID- 25759867
TI  - Achieving optimum carrier concentrations in p-doped SnS thermoelectrics.
AB  - Tin(II)sulfide, SnS, is a commercially viable and environmentally friendly
      thermoelectric material. Recently it was shown how the carrier concentration and
      the thermoelectric power factor can be optimized by Ag-doping in a sulphur rich
      environment. Theoretical calculations lead to a fairly accurate estimation of the
      carrier concentration, whereas the potential of doping with Li(+) is strongly
      overestimated. Two principally ubiquitous effects that can result in decreasing
      the hole concentration, namely the formation of coupled defect complexes and
      oxidation of the dopant, are discussed as possible origins of this disagreement.
      It is shown that oxidation limits the chemical potential of Li beyond that
      already set by the formation of Li2S. This work serves as a comprehensive guide
      to achieve an efficient p-doped SnS thermoelectric material.

PMID- 25759868
TI  - Joint effect of mid- and late-life blood pressure on the brain: the AGES
      Reykjavik Study. Author response.

PMID- 25759869
TI  - Participatory assessment of the health of Latino immigrant men in a community
      with a growing Latino population.
AB  - Latino immigrant men are an understudied population in the US, especially in
      areas with small yet growing Latino populations. For this community-based
      participatory health assessment we conducted four focus groups and 66 structured
      surveys with Latino immigrant men, and 10 openended interviews with service
      providers. We analyzed transcripts using content analysis and survey data using
      Pearson Chi-square tests. Overall, 53% of participating men had not completed
      high school. Our findings suggest that their social circumstances precluded men
      from behaving in a way they believe would protect their health. Loneliness, fear
      and lack of connections prompted stress among men, who had difficulty locating
      healthcare services. Newly immigrated men were significantly more likely to
      experience depression symptoms. Latino immigrant men face social isolation
      resulting in negative health consequences, which are amplified by the new growth
      community context. Men can benefit from interventions aimed at building their
      social connections.

PMID- 25759870
TI  - Health fair report of Asian Americans in Michigan.
AB  - There is little information about Asian American health in Michigan. This
      highlights an urgent need to collect their health data to understand and help
      this fastest growing ethnic group live healthier lives and reduce health
      disparities. Data for about 300 individuals attending two major health fairs were
      collected to study older Chinese and Vietnamese immigrants. The analyses show
      that they have high prevalence rates of hypertension, high cholesterol and
      diabetes, even though their body mass index is relatively low. The report of
      these analyses is a starting point to understand the study groups. Such data can
      help health care providers give sound advice to their patients and allow those of
      us in public health to design proper health programs that may benefit them. But
      more data is needed to include major Asian ethnic groups and identify common
      health concerns among all Asian Americans.

PMID- 25759871
TI  - Preface. Peptide libraries.

PMID- 25759872
TI  - Cloning of a putative extracellular Cu/Zn superoxide  dismutase and functional
      differences of superoxide  dismutases in invasive and indigenous whiteflies.
AB  - Superoxide dismutases (SODs) are a group of important antioxidant defense
      enzymes. In this study, a putative extracellular Cu/Zn superoxide dismutase
      (ecCuZnSOD) complementary DNA was cloned and characterized from the whitefly,
      Bemisia tabaci. Quantitative polymerase chain reaction analysis showed that the
      expression level of BtecCuZnSOD was more than 10-fold higher in the invasive
      Middle East Asia Minor 1 (MEAM1) than in the native Asia II 3 species of the B.
      tabaci species complex. After exposure to low temperature (4  degrees C), the
      expression of Bt-ecCuZnSOD gene was significantly up-regulated in MEAM1 but not
      in Asia II 3. Furthermore, the expression level of B. tabaci intracellular
      CuZnSOD (Bt-icCuZnSOD), Bt-ecCuZnSOD and mitochondrial MnSOD (Bt-mMnSOD) was
      compared after transferring MEAM1 and Asia II 3 whiteflies from favorable
      (cotton) to unfavorable host plants (tobacco). On cotton, both CuZnSOD genes were
      expressed at a higher level in MEAM1 compared with Asia II 3. Interestingly,
      after transferring onto tobacco, the expression of Bt-ecCuZnSOD was significantly
      induced in Asia II 3 but not in MEAM1. On the other hand, while Bt-mMnSOD was
      expressed equally in both species on cotton, Bt-mMnSOD messenger RNA was up
      regulated in MEAM1 on tobacco. Consistently, enzymatic activity assays of CuZnSOD
      and MnSOD demonstrated that CuZnSOD might play an important protective role
      against oxidative stress in Asia II 3, whereas MnSOD activation was critical for
      MEAM1 whiteflies during host adaptation. Taken together, our results suggest that
      the successful invasion of MEAM1 is correlated with its constitutive high
      activity of CuZnSOD and inducible expression of MnSOD under stress conditions.

PMID- 25759873
TI  - Neurosurgery ethics: perspectives from the field, circa 2015.

PMID- 25759874
TI  - [Pierre Bobin].

PMID- 25759875
TI  - Emerging ethical issues in neurosurgery.

PMID- 25759876
TI  - Colorectal cavernous hemangioma in   Klippel-Trenaunay syndrome: a rare   cause
      of abdominal pain and   hematochezia.

PMID- 25759877
TI  - [The benefit of thrombolysis in cerebral infarction--a question of measurements].

PMID- 25759878
TI  - [The clinic--an endangered ecosystem].

PMID- 25759879
TI  - Editorial comment.

PMID- 25759880
TI  - Editorial comment.

PMID- 25759881
TI  - [Also ibuprofen, not just paracetamol, can cause serious liver damage in
      children. NSAIDs should be used with caution in children, as shown in case with
      fatal outcome].

PMID- 25759882
TI  - [Surgical course with focus on intercultural competence. Equal outcomes among
      Swedish and foreign medical students].

PMID- 25759883
TI  - [Structured care for patients with new oral anticoagulants. Nursing based care of
      adults with atrial fibrillation].

PMID- 25759884
TI  - [Cognitive medicine is supported in DSM-5].

PMID- 25759885
TI  - Associating liver partition and portal vein ligation for staged  hepatectomy for
      Klatskin tumours: hinc sunt leones!

PMID- 25759886
TI  - [Swedish neurologists--unusually disobedient when it comes to lumbar punctures].

PMID- 25759887
TI  - Urology nSET 2016: fine tuning of the current programme.

PMID- 25759888
TI  - [Fatalities of fate--in theory and practice].

PMID- 25759889
TI  - Consensus statements in surgery: intra-operative neural monitoring  for thyroid
      surgery.

PMID- 25759890
TI  - Medicine in small doses.

PMID- 25759891
TI  - [Open data important part of future research methodology].

PMID- 25759892
TI  - [High stress level is a threat to medical studies].

PMID- 25759893
TI  - [Physician's role gone astray--time to show the way forward].

PMID- 25759894
TI  - [Web training will strengthen physician's expertise on medicines for elderly].

PMID- 25759895
TI  - ["Learn from Denmark and Norway". Psychologists may be the solution to psychiatry
      shortage of specialists].

PMID- 25759896
TI  - [Time to take responsibility for Parkinson care in Sweden].

PMID- 25759897
TI  - [Restless legs syndrome has been renamed. Willis-Ekbom disease faces possible
      paradigm shift--there is hope for the future].

PMID- 25759898
TI  - [Serious deficiencies in information to coronary patients after balloon
      angioplasty. Patients underestimate the importance of life habits, as shown in
      survey study].

PMID- 25759899
TI  - [Asthma in half of preschool children after early severe bronchial obstruction.
      The same rate now as in the 1980s and 1990s].

PMID- 25759900
TI  - [Bouveret syndrome--when gallstone causes duodenal obstruction. Unusual and very
      difficult diagnosis to make].

PMID- 25759901
TI  - [Modern crisis support requires utilization of new knowledge].

PMID- 25759902
TI  - ["Bear plug"--asbestos source in every home?].

PMID- 25759903
TI  - [The diagnosis coup that changed psychiatry. The story of Robert Spitzer and the
      advent of DSM-III].

PMID- 25759904
TI  - [The metamorphosis of the dogdays].

PMID- 25759906
TI  - Tian jiu therapy for the treatment of asthma in adult patients: a meta-analysis.
AB  - OBJECTIVES: To review and evaluate the efficacy and safety of tian jiu therapy on
      san fu tian for adults with asthma. METHODS: A literature search through August
      31, 2013, was done to identify comparative studies evaluating effective rate,
      pulmonary function, immune response, recurrence rate, quality of life, and
      adverse events. The Cochrane Library, PubMed, EMBASE, and Chinese National
      Knowledge Infrastructure were searched; only randomized controlled trials with
      treatment groups using tian jiu therapy were included. Cochrane Collaboration's
      risk of bias tool and Review Manager software, version 5.2, were used for the
      data synthesis. RESULTS: Six studies involving 657 patients were identified. tian
      jiu therapy was more effective than the control intervention (odds ratio [OR],
      3.51; 95% confidence interval [CI], 2.05-6.00; p<0.00001; I(2)=18%). The
      treatment group had a bigger decrease in IgE level (standard mean difference
      [SMD], -1.40; 95% CI, -2.18 to -0.63; p=0.0004; I(2)=85%) and Eosinophil (Eos)
      level (SMD, -4.26; 95% CI, -6.28 to -2.23; p<0.00001; I(2)=91%) compared with the
      control group. Included studies had a high risk of bias. Few adverse effects were
      reported in the included studies, and no serious adverse responses occurred.
      Adverse effects did not result in any dropouts. CONCLUSIONS: All studies
      indicated that tian jiu therapy has a positive effect on adults with asthma and
      that it is relatively safe because of its noninvasive nature. However, the
      limitations of the research design of the existing studies resulted in high risk
      of bias. More randomized controlled trials of better methodologic quality are
      needed to further confirm efficacy and safety of this therapy.

PMID- 25759905
TI  - Critical asthma syndrome in the ICU.
AB  - Critical asthma syndrome represents the most severe subset of asthma
      exacerbations, and the critical asthma syndrome is an umbrella term for life
      threatening asthma, status asthmaticus, and near-fatal asthma. According to the
      2007 National Asthma Education and Prevention Program guidelines, a life
      threatening asthma exacerbation is marked by an inability to speak, a reduced
      peak expiratory flow rate of <25 % of a patient's personal best, and a failed
      response to frequent bronchodilator administration and intravenous steroids.
      Almost all critical asthma syndrome cases require emergency care, and most cases
      require hospitalization, often in an intensive care unit. Among asthmatics, those
      with the critical asthma syndrome are difficult to manage and there is little
      room for error. Patients with the critical asthma syndrome are prone to
      complications, they utilize immense resources, and they incite anxiety in many
      care providers. Managing this syndrome is anything but routine, and it requires
      attention, alacrity, and accuracy. The specific management strategies of adults
      with the critical asthma syndrome in the hospital with a focus on intensive care
      are discussed. Topics include the initial assessment for critical illness,
      initial ventilation management, hemodynamic issues, novel diagnostic tools and
      interventions, and common pitfalls. We highlight the use of critical care
      ultrasound, and we provide practical guidelines on how to manage deteriorating
      patients such as those with pneumothoraces. When standard asthma management
      fails, we provide experience-driven recommendations coupled with available
      evidence to guide the care team through advanced treatment. Though we do not
      discuss medications in detail, we highlight recent advances.

PMID- 25759907
TI  - Power delivery and self-heating in nanoscale near field transducer for heat
      assisted magnetic recording.
AB  - To keep increasing the storage density in next-generation hard disk drives, heat
      assisted magnetic recording is being developed where a nanoscale near field
      transducer (NFT) locally and temporally heats a sub-diffraction-limited region in
      the recording medium to reduce the magnetic coercivity. This allows the use of
      very small grain in the medium while still maintaining data thermal stability.
      Plasmonic nanostructures made of apertures or antennas are good candidates for
      NFTs because of their capability of subwavelength light manipulation in optical
      frequencies. The NFT must simultaneously deliver enough power to the recording
      medium with as small as possible incident laser power to reduce self-heating in
      the NFT, which could cause thermal expansion and materials failure that lead to
      degradation of the overall hard drive performance. In this work, we study the
      effect of optical properties on the power delivery efficiency of nanoscale bowtie
      aperture antennas, with the presence of a recording media stack. Heat dissipation
      and temperature rise in the NFT are also computed to investigate their dependence
      on materials' properties. The possibility of using alternative plasmonic
      materials for delivering higher power and/or reducing heating in NFTs is
      discussed. 

PMID- 25759908
TI  - Hormonal contraceptives and travel to high altitude.
AB  - Women frequently ask about the safety and efficacy of using hormonal
      contraception (HC), either oral contraceptive pills (OC) or other forms, when
      traveling to high altitude locales. What are the risks and benefits of using HC
      at high altitude? Does HC affect acclimatization, exercise performance, or
      occurrence of acute mountain sickness? This article reviews current data
      regarding the risks and benefits of HC at high altitude, both demonstrated and
      theoretical, with the aim of helping health care providers to advise women
      traveling above 2500 meters. Most healthy women can safely use HC when traveling
      to high altitude, but should be aware of the potential risks and inconveniences.

PMID- 25759909
TI  - 1,5-anhydroglucitol is associated with early-phase insulin secretion in chinese
      patients with newly diagnosed type 2 diabetes mellitus.
AB  - BACKGROUND: The goal of the present study was to explore the correlations of 1,5
      anhydroglucitol (l,5-AG), glycated hemoglobin (HbA1c), and glycated albumin (GA)
      with insulin sensitivity and secretion. SUBJECTS AND METHODS: In total, 302
      patients with newly diagnosed type 2 diabetes mellitus (166 men, 136 women) were
      enrolled in this study. The homeostasis model assessment for insulin resistance
      (HOMA-IR) and homeostasis model assessment for beta-cell function (HOMA-beta)
      were calculated to determine the basal insulin sensitivity and secretion. The
      insulinogenic index (IGI) was used to evaluate early-phase insulin secretion. 1,5
      AG and GA were assayed via the enzymatic method, and HbA1c was detected by high
      pressure liquid chromatography. RESULTS: Among all 302 subjects, the serum 1,5-AG
      level was 13.1+/-7.2 MUg/mL, and the HbA1c and GA levels [median (interquartile
      range)] were 6.7% (6.2-7.3%) and 17.7% (16.0-19.5%), respectively. Increased 1,5
      AG quartiles were accompanied by trends toward a decreased HOMA-IR and an
      increased HOMA-beta and IGI (for all trends, P<0.001). 1,5-AG was negatively
      associated with HOMA-IR (r=-0.200, P<0.001) and positively associated with HOMA
      beta and IGI (r=0.210 and 0.413, respectively; both P<0.001). 1,5-AG was
      independently related to HOMA-IR and HOMA-beta and exhibited an independent
      positive association with IGI (standardized beta=0.242, P<0.001). Additionally,
      both HbA1c and GA were independently correlated with HOMA-IR and HOMA-beta.
      CONCLUSIONS: 1,5-AG is not only correlated with basal insulin sensitivity and
      secretion, but also closely associated with early-phase insulin secretion in
      Chinese patients with newly diagnosed type 2 diabetes mellitus.

PMID- 25759910
TI  - Correction to "Conformational dynamics of the nicotinic acetylcholine receptor
      channel: a 35-ns molecular dynamics simulation study".

PMID- 25759911
TI  - Beyond apoptosis: the mechanism and function of phosphatidylserine asymmetry in
      the membrane of activating mast cells.
AB  - Loss of plasma membrane asymmetry is a hallmark of apoptosis, but lipid bilayer
      asymmetry and loss of asymmetry can contribute to numerous cellular functions and
      responses that are independent of programmed cell death. Exofacial exposure of
      phosphatidylserine occurs in lymphocytes and mast cells after antigenic
      stimulation and in the absence of apoptosis, suggesting that there is a
      functional requirement for phosphatidylserine exposure in immunocytes. In this
      review we examine current ideas as to the nature of this functional role in mast
      cell activation. Mechanistically, there is controversy as to the candidate
      proteins responsible for phosphatidylserine translocation from the internal to
      external leaflet, and here we review the candidacies of mast cell PLSCR1 and
      TMEM16F. Finally we examine the potential relationship between functionally
      important mast cell membrane perturbations and phosphatidylserine exposure during
      activation. 

PMID- 25759912
TI  - Emergent properties of composite semiflexible biopolymer networks.
AB  - The semiflexible polymers filamentous actin (F-actin) and intermediate filaments
      (IF) both form complex networks within the cell, and together are key
      determinants of cellular stiffness. While the mechanics of F-actin networks
      together with stiff microtubules have been characterized, the interplay between F
      actin and IF networks is largely unknown, necessitating the study of composite
      networks using mixtures of semiflexible biopolymers. We employ bulk rheology in a
      simplified in vitro system to uncover the fundamental mechanical interactions
      between networks of the 2 semiflexible polymers, F-actin and vimentin IF.
      Surprisingly, co-polymerization of actin and vimentin can produce composite
      networks either stronger or weaker than pure F-actin networks. We show that this
      effect occurs through steric constraints imposed by IF on F-actin during network
      formation and filament crosslinking, highlighting novel emergent behavior in
      composite semiflexible networks. 

PMID- 25759914
TI  - Craniofacial surgery from China: with admiration for their scholarly
      contributions, innovations and excellence in presentations.

PMID- 25759913
TI  - A moving ParA gradient on the nucleoid directs subcellular cargo transport via a
      chemophoresis force.
AB  - DNA segregation is a critical process for all life, and although there is a
      relatively good understanding of eukaryotic mitosis, the mechanism in bacteria
      remains unclear. The small size of a bacterial cell and the number of factors
      involved in its subcellular organization make it difficult to study individual
      systems under controlled conditions in vivo. We developed a cell-free technique
      to reconstitute and visualize bacterial ParA-mediated segregation systems. Our
      studies provide direct evidence for a mode of transport that does not use a
      classical cytoskeletal filament or motor protein. Instead, we demonstrate that
      ParA-type DNA segregation systems can establish a propagating ParA ATPase
      gradient on the nucleoid surface, which generates the force required for the
      directed movement of spatially confined cargoes, such as plasmids or large
      organelles, and distributes multiple cargos equidistant to each other inside
      cells. Here we present the critical principles of our diffusion-ratchet model of
      ParA-mediated transport and expand on the mathematically derived chemophoresis
      force using experimentally-determined biochemical and cellular parameters. 

PMID- 25759915
TI  - Skeleton first in surgical treatment of facial disharmony.
AB  - PURPOSE: The aim of this study was to correct facial disharmony with or without
      occlusal dysfunction. METHODS: Based on computed tomography and presurgical
      design, restoration of normal skeleton relationship is a priority for selected
      facial deformities. Combination of different osteotomies for facial skeleton was
      chosen in 1-stage operation such as orthognathic surgery, zygomatic reduction,
      and mandibular angle reduction. Supplementary surgeries was considered in some
      cases as substitute implantation or autologous fat graft. RESULTS: All the 50
      patients (hemifacial microsomia, Romberg syndrome, mandibular condyle
      hyperplasia, secondary cleft palate, and Crouzon syndrome) received surgeries,
      and their facial appearance improved significantly. Yearly follow-up shows that
      the symmetry and balance of the facial proportion approach normal, whereas most
      of their occlusal relationship has been significantly improved after the first
      stage of surgery. CONCLUSIONS: For most facial disharmony with or without
      occlusal dysfunction, skeleton-first surgery is a feasible strategy.

PMID- 25759916
TI  - Asymmetric maxillary protraction for unilateral cleft lip and palate patients
      using finite element analysis.
AB  - OBJECTIVE: Unilateral cleft lip and palate (UCLP) patients frequently present
      with an asymmetry in the nasomaxillary complex and a maxillary hypoplasia. The
      aim of this study was to investigate biomechanic effects of asymmetric maxillary
      protraction in UCLP patients using finite element method. METHODS: A finite
      element model of a UCLP patient's skull was generated using data from spiral
      computed tomographic scans. On the basis of this finite element model, three
      groups of orthopedic forces were loaded. All forces were applied in a direction
      that was 30 degrees downward and forward to the occlusal plane on the region of
      the alveolar of the maxillary canine. The value of orthopedic force was 5 N in
      cleft side and 5 N in noncleft side (group A), 6 N in cleft side and 5 N in
      noncleft side (group B), and 7 N in cleft side and 5 N in noncleft side (group
      C), respectively. RESULTS: All 3 groups were effective in promoting maxilla
      forward. In group B, the displacement difference between the cleft side and the
      noncleft side was the smallest. The largest value difference between the cleft
      side and the noncleft side was found in group C. CONCLUSIONS: Maxillary
      protraction with a loading of 6 N in the cleft side and 5 N in the noncleft side
      produced the most favorable outcome. It can be suggested that it might be
      advantageous to perform asymmetric maxillary protraction on UCLP patients.

PMID- 25759917
TI  - The management of pediatric neck masses.
AB  - Neck masses are a common clinical concern both in adults and children. The
      differential diagnosis is quite broad, from congenital lesions to malignant
      tumors. Based on the different pathologic diagnosis, the treatments are varied.
      To the best of our knowledge, limited reports, which specifically discuss the
      incidence and distribution of neck diseases in early childhood, have been
      published. Because of the great population in China, a thorough review of the
      previous clinical data for pediatric neck masses might be potentially valuable
      for oral and maxillofacial surgeons, which might provide a deeper understanding
      and better the accuracy of our clinical diagnosis and management. In this
      article, a 10-year retrospective review was completed; the whole cases were
      diagnosed and treated in the same major clinical institute in east China, which
      might represent as a typical cohort for the patient population and serve as a
      reference for future clinical management. 

PMID- 25759918
TI  - Combined use of rapid-prototyping model and surgical guide in correction of
      mandibular asymmetry malformation patients with normal occlusal relationship.
AB  - OBJECTIVE: The aim of this study is to discuss the application of rapid
      prototyping model and surgical guide in the treatment of mandibular asymmetry
      malformation with normal occlusal relationship. STUDY DESIGN: Twenty-four
      mandibular asymmetry malformation patients with relatively normal occlusal
      relationship were included in this study. Surgical 3-dimensional rapid
      prototyping mandibular models were made for all patients from the computed
      tomography (CT) DICOM data. The presurgical plan was designed on the model, and
      the surgical guiders for the osteotomy lines were manufactured. Genioplasty
      and/or mandibular osteotomy based on the presurgical plan were performed on these
      patients with the combined use of the rapid-prototyping model and surgical
      guides. All patients underwent postoperative CT scan and had at least 3-month
      follow-up. RESULT: All patients were satisfied with the final results. According
      to the postoperative CT images and 3-month follow-up, all patients' mandibular
      asymmetry malformation was significantly improved, and the operation time was
      distinctly shortened relative to the conventional method. CONCLUSION: Rapid
      prototyping model and surgical guide are viable auxiliary devices for the
      treatment of mandibular asymmetry malformation with relatively normal occlusal
      relationship. Combined use of them can make precise preoperative design, improve
      effects of operation, and shorten operating time.

PMID- 25759919
TI  - Neuroendoscopic endonasal management of cerebrospinal fluid rhinorrhea.
AB  - Neuroendoscopic endonasal approach has gained popularity in managing traumatic,
      spontaneous, and especially iatrogenic cerebrospinal fluid (CSF) rhinorrhea. The
      authors examined 8 patients presenting with CSF rhinorrhea between December 2012
      and June 2014: 5 patients had iatrogenic leak, 2 patients had traumatic leak, and
      1 patient had a spontaneous onset of CSF rhinorrhea. Sites of the CSF leaks were
      detected through computed tomographic cisternography and magnetic resonance
      imaging in the patients with traumatic and spontaneous leaks. All patients
      received neuroendoscopic endonasal surgery for the CSF leak. The largest defect
      was 22 mm in maximum diameter. Endoscopic supraciliary "keyhole" approach was
      performed in 1 patient after confirmation of a frontal sinus leak using the
      endoscopic endonasal approach. The success rate was 100% in the first attempt.
      Follow-up period ranged from 3 to 24 months, and no recurrence was reported.
      Identifying the leak site and choosing the appropriate surgical technique remain
      the most important factor in surgical success. 

PMID- 25759920
TI  - Establishment of integral biomechanical balance in the correction of tongue
      source skeletal dentomaxillofacial open bite deformities.
AB  - The objective of this clinical paper is to demonstrate an effective process to
      achieve relative long-term functional and aesthetic stability after the treatment
      of skeletal tongue source open bites. This therapy consisted of applying
      Delaire's architectural analysis as the cephalometry to make treatment plan
      corresponding to the patients' own craniomaxillofacial integral architectural
      structure to achieve the optimal skeletal anteroposterior and vertical position.
      In addition, glossoplasty and transverse matching of upper and lower arches must
      be under consideration in the goal of achieving integral biomechanical functional
      balance and aesthetic harmony. Little relapse of both skeleton and occlusion was
      found more than 3 years posttreatment. The effect of pararthria correction
      coursed by lingual functional impediment is also attained. 

PMID- 25759921
TI  - Second microvascular decompression for trigeminal neuralgia in recurrent cases
      after microvascular decompression.
AB  - OBJECTIVES: The objectives of this work are to report the outcomes of our finding
      during microvascular decompression (MVD) for patients with recurrent trigeminal
      neuralgia (TN) and to introduce the sling retraction technique. METHODS: The
      authors performed a retrospective review of redo MVD for consecutive cases with
      recurrent TN after previous operation. Sling retraction techniques were used
      during the reoperation. RESULTS: Fifteen patients underwent redo MVD. During the
      second operation, arachnoid adhesion of the Teflon felt was confirmed at the
      trigeminal nerve in 10 cases, and neurovascular conflict was found in 4 cases.
      Symptoms were completely relieved in 14 patients (93.3%) and partially relieved
      in 1 patient (6.7%). The mean follow-up period was 38 months (range, 21-60
      months), and no patient experienced recurrence. CONCLUSIONS: Arachnoid adhesion
      of the Teflon felt and vascular compression to the nerve were main causes of
      recurrence. The sling retraction technique is still an effective and useful
      treatment for recurrent TN after MVD.

PMID- 25759922
TI  - Mini-temporalis transposition: a less invasive procedure of smile restoration for
      long-standing incomplete facial paralysis.
AB  - Facial paralysis is a common craniofacial deformity that is responsible for
      significant psychological and functional impairment. Free muscle transfer in 2
      stages and latissimus dorsi transfer in one stage may be the most effective
      surgical procedure for achieving a symmetrical spontaneous smile for a patient
      with complete facial paralysis. However, these 2 procedures are unsuitable for
      many incomplete patients. The authors introduce a less invasive procedure, termed
      mini-temporalis transposition that is able to achieve a symmetrical spontaneous
      smile in incomplete patients. Through a zigzag incision into the temporal region,
      the middle third of the temporalis is transferred and elongated with the palmaris
      longus tendon or combined with the deep temporal fascia. The strips are anchored
      to key points at the modiolus and the middle of the ipsilateral orbicularis oris
      muscle through a small intraoral incision and subcutaneous tunnel. The key points
      are marked during preoperative smile analysis. This procedure was applied to 15
      patients with long-standing incomplete facial paralysis. All patients obtained
      improvements in smile symmetry after the operation, and patients' satisfaction
      was high. In addition, no damage to residual facial nerve functions or
      development of procedure-induced complications (such as a facial contour defect,
      lip eversion or puckering, or skin tethering) was observed in any of the
      patients. Nevertheless, slight temporal hollowing was observed in 4 patients, and
      mild bulkiness over the zygomatic arch was a common observation. In summary, the
      mini-temporalis transfer technique is a safe and effective method of smile
      restoration for long-standing incomplete facial paralysis. 

PMID- 25759923
TI  - A new method of locating foramen rotundum and its anatomic study.
AB  - PURPOSE: The purpose of this study is to provide a new method to locate the
      foramen rotundum (FR) based on the structures in the wall of sphenoid. MATERIALS
      AND METHODS: Computed tomographic angiography images of 172 FR in adults and 10
      bony specimens were reviewed. The measurement was on coronal, sagittal, and axial
      planes after multiplanar reconstruction. The diameter, length, and direction of
      FR were measured. The middle lowest point of sellar region, the sagittal midline,
      and the bottom of sphenoid sinus were selected as the landmarks to locate the FR.
      RESULT: The FR can be found and identified easily on computed tomographic
      angiography image. The bony diameter measured in CT image is in accordance with
      that in specimen. The anterior opening and posterior opening can be located by
      the stationary structures in the sphenoid sinus. CONCLUSIONS: The FR is a
      stationary bony structure; its length, diameter, and angle are relatively
      constant; and it can be easily located by the data measured in this study. The FR
      should be protected in the process of transsphenoid approach as well as be
      precisely located by the procedure about it.

PMID- 25759924
TI  - Treatment of total scalp avulsion by an advanced microsurgical method involving
      the subcutaneous tissue suspension by the tight suture of scalp tissue around
      anastomotic stoma.
AB  - Total scalp avulsion is a rare but challenging surgical trauma to manage. This
      study reports 8 cases of total scalp avulsion between 2001 and 2008. In all these
      cases, the patients were subjected to vascular replantation of the scalp.
      Microvascular technique after the debridement was used for scalp replantation in
      all these patients. Study outcome was that between 2001 and 2004, only 1 case had
      shown major scalp revival and scalp survival whereas in 3 other cases, the scalp
      survival failed. This may be attributed to the poor microscopic anastomosis.
      However, between 2005 and 2008, scalp survival was reported in all the cases,
      which was chiefly due the advanced microsurgical method adopted. In this advanced
      microsurgical technique, the subcutaneous tissue was suspended by the tight
      suture of scalp tissue around the anastomotic stoma, which resulted in scalp
      survival in all the cases. Microsurgical scalp replantation is an effective
      treatment for scalp avulsion. The key to the successful scalp replantation is
      high-quality vascular anastomosis involving subcutaneous tissue suspension via
      the tight suture of scalp tissue around the anastomotic stoma careful
      debridement. 

PMID- 25759925
TI  - The C342R mutation in FGFR2 causes Crouzon syndrome with elbow deformity.
AB  - Crouzon syndrome is an autosomal dominant craniosynostosis syndrome caused by
      mutation in the fibroblast growth factor receptor 2 (FGFR-2). Numerous findings
      from animal studies imply a critical role for FGFRs in the regulation of skeletal
      development. Here, we report 2 unrelated patients with Crouzon syndrome
      accompanied by elbow deformity. Subsequently, we analyzed the sequence of the
      FGFR2 gene and found that both of the patients carried the Cys342Arg mutation.
      The findings suggest that the C342R mutation in FGFR2 may cause Crouzon syndrome
      and elbow deformity in Chinese patients. 

PMID- 25759926
TI  - Abducens nerve schwannoma in cerebellopontine angle mimicking acoustic neuroma.
AB  - The abducens nerve schwannoma is one kind of rare intracranial tumor. We report
      an interesting case of abducens nerve schwannoma in the right cerebellopontine
      angle in a 68-year-old male patient presenting only vertigo and headache, without
      any symptom of abducens nerve palsy. This is the oldest patient with abducens
      nerve schwannoma to date. The patient received a craniectomy via suboccipital
      retrosigmoid approach and had total surgical excision. 

PMID- 25759927
TI  - S267P mutation in FGFR2: first report in a patient with Crouzon syndrome.
AB  - It has been known for several years that mutations in the fibroblast growth
      factor receptor (FGFR2) result in syndromic craniosynostosis including Apert,
      Crouzon, or Pfeiffer syndromes. Here, we report on a child with a clinically
      diagnosed Crouzon syndrome that shows the missense point mutation S267P in FGFR2
      gene. The mutation is firstly identified in Crouzon syndrome. Our observations
      expand the molecular spectrum of FGFR2 mutations in the syndrome. 

PMID- 25759928
TI  - Computer-assisted planning and navigation for the treatment of true hemifacial
      hyperplasia.

PMID- 25759929
TI  - Reconstruction of full-thickness buccal defects with submental island flap.
AB  - Our goal was to introduce the application of submental island flap in
      reconstructing through-and-through cheek defects. From January 2009 to January
      2013, 7 patients (5 men and 2 women) with full-thickness buccal defects due to
      tumor resection received submental flap reconstruction at the Affiliated Tumor
      Hospital of Zhengzhou University; surgical procedure and success rate as well as
      functional results were described. Distal partial necrosis occurred in 1 flap,
      but all flaps survived. All patients were capable of maintaining a regular oral
      diet, and no patients complained of an inability to eat in a public setting,
      microstomia, or drooling; the appearance was reported to be good or acceptable in
      all cases, and the mean postoperative mouth-open width was 4.2 (range, 3.7-5.0)
      cm. One patient had a local recurrence in the follow-up. Therefore, submental
      island flap is a reliable procedure for through-and-through buccal defects in
      selected patients.

PMID- 25759930
TI  - Mattress cerclage combined with electrochemical therapy and pingyangmycin
      injection after embolization for management of arteriovenous malformation on oral
      and maxillofacial region.
AB  - BACKGROUND: The purpose of the article was to assess the clinical results of
      mattress cerclage combined with electrochemical therapy and pingyangmycin
      injection after embolization in treating arteriovenous malformations (AVMs).
      METHODS: During the period from January 2008 to December 2012, a total of 26
      patients with AVMs were treated through mattress cerclage combined with
      electrochemical therapy and pingyangmycin injection after embolization and were
      retrospectively examined. The size of the lesions ranged from 2.5 cm * 3 cm to 8
      cm * 10 cm. The follow-up time varied from 8 months to 24 months. The clinical
      outcome was evaluated using a 4-grade scale. RESULTS: All the lesions decreased
      in size after the treatment. The clinical follow-up showed excellent response in
      20 of the 26 patients, whereas the remaining 6 patients also had satisfactory
      response. The most common complication was swelling, followed by pain and fever,
      without serious adverse effects being encountered. CONCLUSIONS: Mattress cerclage
      combined with electrochemical therapy and pingyangmycin injection after
      embolization was a reliable method for AVMs.

PMID- 25759931
TI  - Severe microphthalmos with cyst and unusually huge dermolipoma.
AB  - PURPOSE: The purpose of this study was to report an unusual case of severe
      microphthalmos, together with an orbital cyst and huge ocular surface
      dermolipoma. METHODS: This is a clinical report relating clinical features as
      well as imaging and histopathologic findings, along with surgical management of
      the patient. RESULTS: A 5-month-old Chinese male infant was referred, with 2
      large masses in the left eye that were present since birth. Ocular examination
      results revealed a complete absence of any eye structures in the left orbit. In
      its place were 2 large masses between the left upper and lower palpebral fissure.
      One was a 3 * 3 * 2.5-cm spherical red tumor with a smooth surface. The other was
      a large solid spherical tumor, 4 * 4 * 5 cm, covered with normal skin located in
      the temporal region and attached to the red mass by a pedicle. Orbital magnetic
      resonance imaging examination findings confirmed that no eye structures were
      present in the left orbit. However, a cystic lesion was found in the left orbit,
      with a low signal on T1-weighted imaging and high signal on T2-weighted imaging,
      and another huge spherical heterogeneous mass was located "outside" the left
      orbit. Anterior orbitotomy by conjunctival incision was performed under general
      anesthesia. A spherical cystic mass of 1.5 * 1.5 * 1.6 cm, a small eye of 0.7 *
      0.7 * 0.6 cm, and a huge dermolipoma were removed completely. Pathologic
      examination results confirmed the diagnosis of severe microphthalmos, together
      with orbital dermoid cyst and dermolipoma. CONCLUSIONS: This rare case
      demonstrates that severe microphthalmos with a cyst may be completely covered by
      conjunctiva and associated with an unusually huge dermolipoma.

PMID- 25759932
TI  - miR-495 mediates metabolic shift in glioma cells via targeting Glut1.
AB  - Cancer cell metabolism is often characterized by a shift from an oxidative to a
      glycolytic bioenergetics pathway, a phenomenon known as the Warburg effect.
      Whether the deregulation of microRNAs contributes to the Warburg effect remains
      largely unknown. Here, we show that miR-495 expression is decreased and thus
      induces a metabolic shift in glioma cells. miR-495 performs this function by
      increasing the expression of Glut1, leading to the increase of glucose uptake and
      lactate production. The altered metabolism induced by miR-495 results in the
      rapid growth of cancer cells. These results identify miR-495 as a molecular
      switch involved in the orchestration of the Warburg effect in glioma cells via
      targeting the expression of Glut1.

PMID- 25759933
TI  - Reconstruction of upper lip scar using tissue expander advancement flap.
AB  - Some patients who previously underwent burns have upper lip deformities or
      extensive scars so they seek for treatments.We reported a patient who had
      extensive scars all over the upper lip. In the patient's case, we reconstructed
      the entire upper lip using a tissue expander advancement flap from the bilateral
      lip. This improved the upper lip contracture and appearance. The removal of the
      scar from the upper lip provided a satisfactory result.The use of 2 large tissue
      expander advancement flaps from the bilateral upper lip has several advantages,
      such as inconspicuous scar, nice skin texture, and color match. 

PMID- 25759934
TI  - Gorham disease of the mandible.
AB  - Gorham disease, or massive osteolysis, is a rare condition of unknown etiology.
      The disease is characterized by spontaneous progressive osteolysis of 1 or more
      skeletal bones. The mandible is the most commonly involved bone in the
      maxillofacial region. This article reports a case of Gorham disease with
      mandibular involvement in a 46-year-old male patient with a 7-year follow-up. In
      this case, we performed lower right mandibular osteotomy and reconstruction with
      a phased titanium plate. Postoperative follow-up showed continued mandibular bone
      loss that was progressing to the contralateral mandible. Massive osteolysis of
      the mandible is a rare clinical condition that must be differentiated from
      mandibularosteomyelitis, benign and malignant tumors, as well as
      hyperparathyroidism. Improved differential diagnoses and disease follow-up are
      required to effectively manage massive osteolysis.

PMID- 25759935
TI  - Tumor recurrence and complications of parotidectomy using the marginal mandibular
      branch as a landmark during the retrograde technique.
AB  - PURPOSE: To investigate the recurrence of tumors and morbidity rates of
      postoperative complications associated with primary parotid pleomorphic adenomas
      treated with a parotidectomy using the marginal mandibular branch of the facial
      nerve as a landmark during the retrograde approach. PATIENTS AND METHODS: Our
      study retrospectively analyzed the clinical data from 71 patients with a primary
      parotid pleomorphic adenoma who underwent a parotidectomy using the marginal
      mandibular branch of the facial nerve as a guide during the retrograde approach
      between November 2003 and August 2012. Three surgical modalities were involved in
      the study: a partial superficial parotidectomy was performed in 8 cases, a
      superficial parotidectomy was performed in 54 cases, and a total parotidectomy
      was performed in 9 cases. The recurrence of tumors and the morbidity rates of
      postoperative complications, such as transient facial nerve paralysis, permanent
      facial nerve paralysis, sensory deficiency, Frey syndrome, salivary fistulas, and
      xerostomia, were investigated. RESULTS: Tumor recurrence occurred in only 1 case.
      Overall, the morbidity rates for transient facial nerve paralysis, permanent
      facial nerve paralysis, sensory deficiency, Frey syndrome, and xerostomia were
      22.5%, 1.4%, 39.4%, 59.2%, and 8.5%, respectively. No cases developed a salivary
      fistula. CONCLUSION: The use of the marginal mandibular branch of the facial
      nerve as a guide during the retrograde approach is a reliable and safe method for
      dissecting the facial nerve.

PMID- 25759936
TI  - Changes in the temporomandibular joint space after functional treatment of disk
      displacement with reduction.
AB  - This study aimed to evaluate the changes of temporomandibularjoint (TMJ) space in
      the treatment of disk displacement with reduction (DDWR) for class II cases.
      Forty-two adolescent patients with unilateral DDWR, who were successfully treated
      by functional appliance, were selected in this study. Magnetic resonance imaging
      scans were used before treatment (T1), at the start of treatment (T2), and after
      functional treatment (T3). Compared with the normal joint, the change of joint
      space index was calculated. The anterior, posterior, and superior joint spaces
      were analyzed on the largest sagittal plane among T1, T2, and T3. Student's t
      test was used for statistical analysis. The mean treatment period was 10 months
      (6-16 mo). Functional appliance was effective in eliminating pain and clicking.
      During the phase of T1, the value of the joint space index of DDWR was
      significantly higher than that of the control (P < 0.05). There was a significant
      decrease in the anterior space and an increase in the postsuperior space at T2 (P
      < 0.01), and then the contrary changes occurred at T3. However, there was a
      significant increase in the postsuperior space and no significant decrease in the
      anterior space when T1 and T3 were compared. This study indicates that the TMJ
      space is well distributed after disk repositioning with functional treatment of
      DDWR. It is also suggested that the adaptive remodeling in TMJ occurs via
      functional treatment. 

PMID- 25759937
TI  - The roles of emotion dysregulation and dissociation in the association between
      sexual abuse and self-injury among juvenile justice-involved youth.
AB  - To date, scholars have established associations among nonsuicidal self-injury and
      sexual abuse, posttraumatic stress symptoms, and dissociation. However, leading
      theoretical models of the mechanisms underlying the association between trauma
      and negative outcomes suggest a more parsimonious explanation in that deficits in
      emotion regulation may underlie these various risk factors for self-injury. This
      study examined whether sexual abuse was differentially associated with
      nonsuicidal self-injury over and above other forms of traumatic experiences and
      whether the association between sexual abuse and self-injury was statistically
      mediated by emotion dysregulation and dissociation. Participants included 525
      youth (392 boys, 133 girls) recruited from the U.S. juvenile justice system who
      completed measures of self-reported trauma exposure, posttraumatic stress
      symptoms, dissociation, and emotion dysregulation. Results of a hierarchical
      regression demonstrated that sexual abuse predicted posttraumatic stress symptoms
      and self-injury over and above other forms of traumatic experiences. Results of
      bootstrapped mediation analyses indicated that emotion dysregulation and
      dissociation in combination were implicated in self-injury among youth. The
      results suggest that youth in the juvenile justice system who experience sexual
      abuse may be at risk for higher rates of posttraumatic stress symptoms and that
      self-injury may be particularly salient for youth who experience sexual abuse.
      Furthermore, the results shed light on the role that dissociation and emotion
      dysregulation play in the relation between sexual abuse and self-injury,
      suggesting that a larger framework of self-regulation may have both empirical and
      clinical utility in helping to understand the underlying processes at play in
      these associations. 

PMID- 25759938
TI  - Regulation Policy on Cell- and Tissue-Based Therapy Products in Korea.
AB  - Extensive investment on research and development of cell therapy products (CTPs)
      and tissue-engineered products (TEPs) has been made in Korea, and various
      commercial products are born in market. The Ministry of Food and Drug Safety
      (MFDS) in Korea regulates CTPs and TEPs as biological products under the
      authority of the Pharmaceutical Affairs Act. The Korean MFDS approved 16 CTPs and
      4 stem CTPs and authorized 135 clinical trials, including 60 sponsor-investigator
      trials. Currently, the advent of stem cell technology and new biomaterials gives
      an impetus to develop more innovative CTPs and TEPs to treat intractable and
      serious diseases. This article deals about the regulatory process for approving
      CTPs and TEPs in Korea. Regulatory policies of the MFDS for supporting the
      development of novel products and ensuring the safety of the CTPs and TEPs are
      reviewed. 

PMID- 25759939
TI  - Rhodium catalyzed arylation of diazo compounds with aryl boronic acids.
AB  - A general and efficient synthesis of diarylacetate, a diarylmethine derivative,
      was accomplished through rhodium catalyzed direct arylation of diazo compounds
      with arylboronic acids. The reaction tolerates various boronic acid derivatives
      and functional groups. Notably, chemoselective arylation of diazo compounds over
      other electrophiles were demonstrated. The efficacy of the developed methodology
      is shown by the expeditious synthesis of the core structure of diclofensine. 

PMID- 25759940
TI  - The driving forces for twisted or planar intramolecular charge transfer.
AB  - A D-A (donor-acceptor)-type chromophore may twist or flatten in its excited state
      to form a TICT (twisted intramolecular charge transfer) state or a PICT (planar
      intramolecular charge transfer) state, respectively. What is the driving force
      behind this twisting or planarization? Which geometry will occur for a certain D
      A chromophore? To answer these questions, both fragment orbital interaction and
      excited state energy decomposition analyses were performed on several classical
      TICT/PICT molecules. Three driving forces were identified, namely, energy gap,
      hole-electron interactions, and excited state relaxation. The contributions of
      these driving forces in various types of molecules were analyzed to determine how
      the molecular structure affects them. The energy gap difference between the
      twisted and planar geometries was found to play a decisive role in most
      situations. Thus, evaluating the frontier orbital interactions between the donor
      and acceptor effectively predicts whether chromophores planarize or twist in the
      excited state. 

PMID- 25759941
TI  - Attractive design: an elution solvent optimization platform for magnetic-bead
      based fractionation using digital microfluidics and design of experiments.
AB  - There is great interest in the development of integrated tools allowing for
      miniaturized sample processing, including solid phase extraction (SPE). We
      introduce a new format for microfluidic SPE relying on C18-functionalized
      magnetic beads that can be manipulated in droplets in a digital microfluidic
      platform. This format provides the opportunity to tune the amount (and
      potentially the type) of stationary phase on-the-fly, and allows the removal of
      beads after the extraction (to enable other operations in same device-space),
      maintaining device reconfigurability. Using the new method, we employed a design
      of experiments (DOE) operation to enable automated on-chip optimization of
      elution solvent composition for reversed phase SPE of a model system. Further,
      conditions were selected to enable on-chip fractionation of multiple analytes.
      Finally, the method was demonstrated to be useful for online cleanup of extracts
      from dried blood spot (DBS) samples. We anticipate this combination of features
      will prove useful for separating a wide range of analytes, from small molecules
      to peptides, from complex matrices. 

PMID- 25759942
TI  - A randomized controlled pilot trial of acceptance and commitment training (ACT)
      for preventing stress-related ill health among future nurses.
AB  - BACKGROUND: Levels of stress and burnout increase during nursing education. This
      development has consequences for nursing students' health, learning, competence,
      and interest in quality issues in health care. DESIGN: In a randomized controlled
      pilot trial with a sample of 113 nursing students the effect of an intervention
      using techniques from acceptance and commitment training (ACT) to prevent the
      development of stress and burnout was evaluated. METHOD: The 6 * 2-hour program
      was compared to standard treatment (reflection seminars) post-intervention and at
      a three-month follow-up using longitudinal analysis of mean response profiles.
      Mechanisms of change were investigated using a baseline-post intervention two
      mediator model. RESULTS: The intervention resulted in increased mindful awareness
      and decreased experiential avoidance, as well as decreased perceived stress and
      burnout. Levels of mindful awareness and perceived stress were sustained at
      follow-up. The proposed mechanisms of change were partly supported by the data.
      CONCLUSION: This study shows that techniques from ACT might have the potential to
      contribute to preventing the development of stress and burnout during nursing
      education. However, additional studies are needed to validate these results.

PMID- 25759943
TI  - Findings on early treatment response assessment with 18F-FDG PET/CT as a pointer
      toward a 'second-look' at the diagnosis: an ancillary observation but with
      potential implications for patient management in a multidisciplinary setting.

PMID- 25759944
TI  - Does 18F-FDG PET/MRI reduce the number of indeterminate abdominal incidentalomas
      compared with 18F-FDG PET/CT?
AB  - OBJECTIVE: Incidental masses of abdominal organs are a relevant problem in
      radiological examinations. The aim of this study was to evaluate whether
      simultaneous (18)F-fluorodeoxyglucose ((18)F-FDG) PET/MRI, because of its higher
      soft-tissue contrast and the diversity of available pulse sequences, can reduce
      the number of indeterminate abdominal incidentalomas compared with (18)F-FDG
      PET/computed tomography (CT). MATERIALS AND METHODS: In this retrospective study,
      we enrolled 173 patients (91 women and 82 men, mean age 55.8+/-14.6 years) who
      underwent contrast-enhanced (18)F-FDG PET/CT on the same day for oncological
      indications. Data sets were examined in a random order by two readers noting
      incidentalomas and incidental tracer uptake of the liver, kidneys, spleen,
      pancreas, adrenal glands, and gallbladder. Findings were categorized into three
      categories: most likely malignant, indeterminate, and most likely benign. In
      addition, the most relevant MR sequence for the final decision was recorded for
      each incidentaloma. The numbers of benign, indeterminate, and malignant findings
      on (18)F-FDG PET/CT and (18)F-FDG PET/MRI were compared. A subgroup analysis was
      carried out to detect potential differences with respect to lesion location
      (organwise) and lesion consistency (solid vs. cystic). RESULTS: A total of 649
      upper abdominal incidentalomas were found. (18)F-FDG PET/MRI detected more
      incidentalomas (n=635) than contrast-enhanced (18)F-FDG PET/CT (n=407, P<0.001).
      Using (18)F-FDG PET/MRI, significantly fewer incidentalomas were categorized as
      indeterminate compared with (18)F-FDG PET/CT (n=27 vs. 91, P<0.001). This was
      true for cystic (P<0.001) as well as solid masses (P<0.001). Seventy
      incidentalomas categorized as indeterminate on contrast-enhanced (18)F-FDG PET/CT
      could be clarified as most likely benign by (18)F-FDG PET/MRI, whereas only six
      lesions rated as benign by (18)F-FDG PET/CT were classified as indeterminate in
      (18)F-FDG PET/MRI. (18)F-FDG PET/MRI compared with contrast-enhanced (18)F-FDG
      PET/CT had significantly fewer indeterminate findings in the liver (P<0.001),
      kidneys (P=0.012), and adrenal glands (P=0.002); differences for the spleen
      (P=0.5) were not significant. CONCLUSION: (18)F-FDG PET/MRI identifies more
      incidentalomas than (18)F-FDG PET/CT, but significantly reduces the number of
      indeterminate incidental findings of abdominal organs.

PMID- 25759945
TI  - Efficacy of equilibrium radionuclide angiography to predict acute response to
      cardiac resynchronization therapy in patients with heart failure.
AB  - OBJECTIVE: To predict the acute response to cardiac resynchronization therapy
      (CRT) in patients with left ventricular mechanical dyssynchrony using equilibrium
      radionuclide angiography (ERNA). PATIENTS AND METHODS: A total of 24 consecutive
      heart failure patients scheduled for CRT were included. ERNA was performed before
      and within 48 h after pacemaker implantation to calculate both left ventricular
      (LV) volumes and LV dyssynchrony. LV dyssynchrony was defined as the standard
      left ventricular phase shift and left ventricular phase standard deviation (LVPS%
      and LVPSD%). Patients were subsequently divided into acute responders or
      nonresponders, based on a reduction of at least 15% in LV end-systolic volume
      immediately after CRT. RESULTS: Fifteen patients (63%) were classified as acute
      responders. Baseline characteristics were similar between responders and
      nonresponders except for the LVPS% and LVPSD%, which were larger in responders.
      Moreover, responders demonstrated a significant reduction of LVPS% and LVPSD%
      immediately after CRT (from 28.00+/-2.88 to 17.53+/-4.94 and 11.20+/-2.54 to
      5.60+/-1.80, P<0.001), whereas in nonresponders LVPS% and LVPSD% remained
      unchanged (from 21.44+/-3.91 to 19.56+/-4.22% and 6.55+/-1.51 to 6.22+/-1.30%,
      P=NS). Receiver operating characteristic curve analysis revealed that a cut-off
      value of 25% for LVPS%, a sensitivity of 80% with a specificity of 89% were
      obtained to predict acute ERNA response to CRT (area under the curve=0.93) and a
      cut-off value of 8.5% for LVPSD%, a sensitivity of 87% with a specificity of 89%
      were obtained to predict acute ERNA response to CRT (area under the curve=0.95).
      CONCLUSION: ERNA is highly predictive for acute response to CRT. ERNA also allows
      assessment of changes in LV volumes and LV ejection fraction before and after CRT
      implantation.

PMID- 25759946
TI  - Synthesis of a stabilized 177Lu-siRNA complex and evaluation of its stability and
      RNAi activity.
AB  - PURPOSE: Serum and intracellular instability limits the therapeutic applications
      of short interfering RNA (siRNA) as a radiopharmaceutical. Chemical modifications
      like phosphorothioate (PS) substitution and 2'-O-methoxy (2'-O-Me) modifications
      could eliminate such limitations. In this study, the effects of PS and 2'-O-Me
      modifications at the backbone of siRNA on serum stability and RNA interference
      activity were investigated. MATERIALS AND METHODS: Fully PS and 2'-O-Me-modified
      type 1 insulin-like growth factor receptor (IGF-1R) siRNA was radiolabeled with
      lutetium-177 ((177)Lu) through p-SCN-Bn-DTPA as a chelator. After purification
      with Vivaspin and PD-10 columns, the radiolabs were examined for stability in
      serum by instant thin-layer chromatography and polyacrylamide gel
      electrophoresis. The level of IGF-1R in response to the modified and labeled IGF
      1R siRNA was examined using RT-PCR and ELISA assay in colon cancer cells. The
      effects of such siRNA on the prevention of proliferation of colon cancer cells
      and its apoptosis were investigated using MTT assay and Annexin-V/propidium
      iodide double staining, respectively. Cellular accumulation quantities of the
      labeled and modified IGF-1R siRNA were determined using a gamma-counter by taking
      advantage of (177)Lu as a gamma-emitter. RESULTS: Both the modified (177)Lu-siRNA
      complex and the modified nonlabeled siRNA showed significant stability in serum.
      The levels of IGF-1R mRNA and protein significantly decreased with both the
      labeled and nonlabeled IGF-1R siRNAs, but no such reduction in IGF-1R was
      observed with luciferase siRNA (P<0.01). Proliferation decreased significantly
      and apoptosis increased in the cells treated with modified (177)Lu-IGF-1R siRNA
      in comparison with either (177)Lu or labeled luciferase siRNA (P<0.001).
      CONCLUSION: Uniform chemically modified siRNAs can form stable complexes with Lu
      that pronounce its cytotoxic effect through apoptosis in colon cancer cells.

PMID- 25759947
TI  - Meta-analysis of the effect of goal-directed therapy on bowel function after
      abdominal surgery.
AB  - BACKGROUND: Intraoperative goal-directed therapy (GDT) was introduced to titrate
      intravenous fluids, with or without inotropic drugs, based on objective measures
      of hypovolaemia and cardiac output measurements to improve organ perfusion. This
      meta-analysis aimed to determine the effect of GDT on the recovery of bowel
      function after abdominal surgery. METHODS: MEDLINE, Embase, the Cochrane Library
      and PubMed databases were searched for randomized clinical trials and cohort
      studies, from January 1989 to June 2013, that compared patients who did, or did
      not, receive intraoperative GDT, and reported outcomes on the recovery of bowel
      function. Time to first flatus and first bowel motion, time to tolerate oral
      diet, postoperative nausea and vomiting, and primary postoperative ileus were
      included. RESULTS: Thirteen trials with 1399 patients were included in the
      analysis. GDT shortened the time to the first bowel motion (weighted mean
      difference (WMD -0.67, 95 per cent c.i. -1.23 to -0.11; P = 0.020) and time to
      tolerate oral intake (WMD -0.95, -1.81 to -0.10; P = 0.030), and reduced
      postoperative nausea and vomiting (risk difference -0.15, -0.26 to -0.03; P =
      0.010). When only high-quality studies were included, GDT reduced only the time
      to tolerate oral intake (WMD -1.18, -2.03 to -0.33; P = 0.006). GDT was more
      effective outside enhanced recovery programmes and in patients undergoing
      colorectal surgery. CONCLUSION: GDT facilitated the recovery of bowel function,
      particularly in patients not treated within enhanced recovery programmes and in
      those undergoing colorectal operations.

PMID- 25759948
TI  - Cu(II)-catalyzed transformation of benzylpenicillin revisited: the overlooked
      oxidation.
AB  - Penicillins, a class of widely used beta-lactam antibiotics, are known to be
      susceptible to catalyzed hydrolysis by metal ions such as Cu(II). However, new
      results in this study strongly indicate that the role of Cu(II) is not merely a
      hydrolysis catalyst but also an oxidant. When benzylpenicillin (i.e., penicillin
      G (PG)) was exposed to Cu(II) ion at an equal molar ratio and pH 7, degradation
      of PG occurred rapidly in the oxygen-rich solution but gradually slowed down to a
      halt in the oxygen-limited solution. In-depth studies revealed that Cu(II)
      catalyzed hydrolysis of PG to benzylpenicilloic acid (PA) and oxidized PA to
      yield phenylacetamide and other products. The availability of oxygen played the
      role in reoxidizing Cu(I) back to Cu(II), which sustained fast degradation of PG
      over time. The overall reaction was also influenced by pH, with Cu(II)-catalyzed
      hydrolysis of PG occurring throughout pH 5, 7 and 9, while Cu(II) oxidation of PA
      occurring at pH 7 and 9. Note that the potential of Cu(II) to oxidize penicillins
      was largely overlooked in the previous literature, and catalyzed hydrolysis was
      frequently assumed as the only reaction. This study is among the first to
      identify the dual roles of Cu(II) in the entire degradation process of PG and
      systematically investigate the overlooked oxidation reaction to elucidate the
      mechanism. The new mechanistic knowledge has important implications for many
      other beta-lactam antibiotics for their interactions with Cu(II), and
      significantly improves the ability to predict the environmental fate and
      transformation products of PG and related penicillins in systems where Cu(II)
      species are also present. 

PMID- 25759949
TI  - Management of squamous cell and basal cell carcinomas of the head and neck with
      perineural invasion.
AB  - Perineural invasion (PNI) occurring in non-melanoma skin cancers (NMSC) is
      associated with an increased risk of locoregional recurrence and reduced disease
      free survival. This necessitates early and accurate diagnosis, appropriate risk
      stratification and a clear management strategy. The diagnosis of PNI is based on
      careful clinical assessment, imaging and histopathology. Surgery, preferably with
      margin control, and definitive or adjuvant radiotherapy (ART) are established
      treatment strategies for PNI. Clinical uncertainty remains over the role of ART
      in incidental PNI. This review synthesises current literature to ascertain which
      clinicopathological features impart a higher risk to individuals with PNI in
      NMSC, in order to provide treatment algorithms, including the identification of
      patient subsets that are most likely to benefit from ART. This includes those
      with extratumoural PNI, involvement of larger-calibre nerves, tumour invasion
      beyond dermis, recurrent tumour or diffuse intratumoural spread. Patients with
      clinical PNI may be optimally managed by a multidisciplinary head and neck cancer
      service that is best placed to offer skull base surgery and intensity-modulated
      radiation therapy (IMRT). The management options presented are stratified by
      histological subtype and a new classification of PNI into low-risk, medium-risk
      and high-risk groups. 

PMID- 25759950
TI  - Tensile strained germanium nanowires measured by photocurrent spectroscopy and X
      ray microdiffraction.
AB  - Applying tensile strain in a single germanium crystal is a very promising way to
      tune its bandstructure and turn it into a direct band gap semiconductor. In this
      work, we stress vapor-liquid-solid grown germanium nanowires along their [111]
      axis thanks to the strain tranfer from a silicon nitride thin film by a
      microfabrication process. We measure the Gamma-LH direct band gap transition by
      photocurrent spectrometry and quantify associated strain by X-ray Laue
      microdiffraction on beamline BM32 at the European Synchrotron Radiation Facility.
      Nanowires exhibit up to 1.48% strain and an absorption threshold down to 0.73 eV,
      which is in good agreement with theoretical computations for the Gamma-LH
      transition, showing that the nanowire geometry is an efficient way of applying
      tensile uniaxial stress along the [111] axis of a germanium crystal. 

PMID- 25759951
TI  - pH-Responsive chimaeric pepsomes based on asymmetric poly(ethylene glycol)-b
      poly(l-leucine)-b-poly(l-glutamic acid) triblock copolymer for efficient loading
      and active intracellular delivery of doxorubicin hydrochloride.
AB  - pH-Responsive chimaeric polypeptide-based polymersomes (refer to as pepsomes)
      were designed and developed from asymmetric poly(ethylene glycol)-b-poly(l
      leucine)-b-poly(l-glutamic acid) (PEG-PLeu-PGA, PEG is longer than PGA) triblock
      copolymers for efficient encapsulation and triggered intracellular delivery of
      doxorubicin hydrochloride (DOX.HCl). PEG-PLeu-PGA was conveniently prepared by
      sequential ring-opening polymerization of l-leucine N-carboxyanhydride and gamma
      benzyl-l-glutamate N-carboxyanhydride using PEG-NH2 as an initiator followed by
      deprotection. Pepsomes formed from PEG-PLeu-PGA had unimodal distribution and
      small sizes of 64-71 nm depending on PLeu block lengths. Interestingly, these
      chimaeric pepsomes while stable at pH 7.4 were quickly disrupted at pH 5.0,
      likely due to alternation of ionization state of the carboxylic groups in PGA
      that shifts PGA blocks from hydrophilic and random coil structure into
      hydrophobic and alpha-helical structure. DOX.HCl could be actively loaded into
      the watery core of pepsomes with a high loading efficiency. Remarkably, the in
      vitro release studies revealed that release of DOX.HCl was highly dependent on
      pH, in which about 24.0% and 75.7% of drug was released at pH 7.4 and 5.0,
      respectively, at 37  degrees C in 24 h. MTT assays demonstrated that DOX.HCl
      loaded pepsomes exhibited high antitumor activity, similar to free DOX.HCl in RAW
      264.7 cells. Moreover, they were also potent toward drug-resistant MCF-7 cancer
      cells (MCF-7/ADR). Confocal microscopy studies showed that DOX.HCl-loaded
      pepsomes delivered and released drug into the cell nuclei of MCF-7/ADR cells in 4
      h, while little DOX.HCl fluorescence was observed in MCF-7/ADR cells treated with
      free drug under otherwise the same conditions. These chimaeric pepsomes with
      facile synthesis, efficient drug loading, and pH-triggered drug release behavior
      are an attractive alternative to liposomes for targeted cancer chemotherapy. 

PMID- 25759952
TI  - Correction: Chapman, E.; et al. Inhibitors of the AAA+ chaperone p97. Molecules
      2015, 20, 3027-3049.

PMID- 25759953
TI  - "In-plant" NMR: analysis of the intact plant Vesicularia dubyana by high
      resolution NMR spectroscopy.
AB  - We present here the concept of "in-plant" NMR and show that high-resolution NMR
      spectroscopy is suitable for the analysis of intact plants and can be used to
      follow the changes in the intraorganismal molecular composition over long time
      periods. The NMR-based analysis of the effect of different concentrations of
      heavy water on the aquatic plant Vesicularia dubyana revealed that due to the
      presence of specific adaptive mechanisms this plant can sustain the presence of
      up to 85% of D2O. However, it dies in 100% heavy water. 

PMID- 25759954
TI  - Self-assembled polyelectrolyte nanoparticles as fluorophore-free contrast agents
      for multicolor optical imaging.
AB  - In this work, we describe the fabrication of self-assembled polyelectrolyte
      nanoparticles that provide a multicolor optical imaging modality. Poly(gamma
      glutamic acid)(gamma-PGA) formed self-assembled nanoparticles through
      electrostatic interactions with two different cationic polymers: poly(L
      lysine)(PLL) and chitosan. The self-assembled gamma-PGA/PLL and gamma
      PGA/chitosan nanoparticles were crosslinked by glutaraldehyde. Crosslinking of
      the ionic self-assembled nanoparticles with glutaraldehyde not only stabilized
      the nanoparticles but also generated a strong autofluorescence signal.
      Fluorescent Schiff base bonds (C=N) and double bonds (C=C) were generated
      simultaneously by crosslinking of the amine moiety of the cationic
      polyelectrolytes with monomeric glutaraldehyde or with polymeric glutaraldehyde.
      The unique optical properties of the nanoparticles that resulted from the
      crosslinking by glutaraldehyde were analyzed using UV/Vis and fluorescence
      spectroscopy. We observed that the fluorescence intensity of the nanoparticles
      could be regulated by adjusting the crosslinker concentration and the reaction
      time. The nanoparticles also exhibited high performance in the labeling and
      monitoring of therapeutic immune cells (macrophages and dendritic cells). These
      self-assembled nanoparticles are expected to be a promising multicolor optical
      imaging contrast agent for the labeling, detection, and monitoring of cells. 

PMID- 25759955
TI  - Synthesis and antifungal activity of the derivatives of novel pyrazole
      carboxamide and isoxazolol pyrazole carboxylate.
AB  - A series of pyrazole carboxamide and isoxazolol pyrazole carboxylate derivatives
      were designed and synthesized in this study. The structures of the compounds were
      elucidated based on spectral data (infrared, proton nuclear magnetic resonance
      and mass spectroscopy). Then, all of the compounds were bioassayed in vitro
      against four types of phytopathogenic fungi (Alternaria porri, Marssonina
      coronaria, Cercospora petroselini and Rhizoctonia solani) using the mycelium
      growth inhibition method. The results showed that some of the synthesized
      pyrazole carboxamides displayed notable antifungal activity. The isoxazole
      pyrazole carboxylate 7ai exhibited significant antifungal activity against R.
      solani, with an EC50 value of 0.37 MUg/mL. Nonetheless, this value was lower than
      that of the commercial fungicide, carbendazol.

PMID- 25759956
TI  - Phytochemicals and other characteristics of Croatian monovarietal extra virgin
      olive oils from Oblica, Lastovka and Levantinka varieties.
AB  - Virgin olive oils from the fruits of Croatian autochthonous varieties Oblica,
      Lastovka and Levantinka were characterized for the first time. Headspace
      volatiles were analyzed by HS-SPME/GC-FID/MS. The main volatiles were C6
      compounds. The most abundant was (E)-hex-2-enal (62.60%-69.20%). (Z)-Hex-3-enal
      was not found in Lastovka oil, while Levantinka oil did not contain hexanal.
      Tocopherols, chlorophylls and carotenoids were determined by HPLC-FL. Levantinka
      oil was characterized by the highest alpha-tocopherol level (222.00 mg/kg). Total
      phenolic contents (TPs), as well as antioxidant activity (DPPH assay) of the oils
      hydrophilic fractions (HFs) were assessed by spectroscopic methods. The
      antioxidant activity of Oblica oil HF was the most pronounced (0.91 mmol TEAC/kg)
      and the HF contained the highest TPs amount (212.21 mg/kg). HFs phenolic
      composition was determined by HPLC-DAD. The main identified phenols were
      secoiridoids dominated in Oblica oil: decarboxymethyl ligstroside aglycone (p
      HPEA-EDA up to 158.5 mg/kg), oleuropein aglycone (3,4-HPEA-EA up to 96.4 mg/kg)
      and decarboxymethyl oleuropein aglycon (3,4-DHPEA-EDA up to 93.5 mg/kg).

PMID- 25759957
TI  - Phaleria macrocarpa Boerl. (Thymelaeaceae) leaves increase SR-BI expression and
      reduce cholesterol levels in rats fed a high cholesterol diet.
AB  - In vitro and in vivo studies of the activity of Phaleria macrocarpa Boerl
      (Thymelaeaceae) leaves against the therapeutic target for hypercholesterolemia
      were done using the HDL receptor (SR-BI) and hypercholesterolemia-induced Sprague
      Dawley rats. The in vitro study showed that the active fraction (CF6) obtained
      from the ethyl acetate extract (EMD) and its component 2',6',4-trihydroxy-4'
      methoxybenzophenone increased the SR-BI expression by 95% and 60%, respectively.
      The in vivo study has proven the effect of EMD at 0.5 g/kgbw dosage in reducing
      the total cholesterol level by 224.9% and increasing the HDL cholesterol level by
      157% compared to the cholesterol group. In the toxicity study, serum glutamate
      oxalate transaminase (SGOT) and serum glutamate pyruvate transaminase (SGPT)
      activity were observed to be at normal levels. The liver histology also proved no
      toxicity and abnormalities in any of the treatment groups, so it can be
      categorized as non-toxic to the rat liver. The findings taken together show that
      P. macrocarpa leaves are safe and suitable as an alternative control and
      prevention treatment for hypercholesterolemia in Sprague Dawley rats.

PMID- 25759958
TI  - Selective TERS detection and imaging through controlled plasmonics.
AB  - Enhanced Raman spectroscopy offers capabilities to detect molecules in the
      complex molecular environments and image chemical heterogeneity in a wide range
      of samples. It has been shown that plasmonic interactions between a TERS tip and
      a metal surface produce significant enhancements. In this report we show how SERS
      spectra from purified molecules can be used to selectively image proteins on
      surfaces and in cell membranes. The SERS response from the purified protein can
      be used to create a multivariate regression model that can be applied to
      nanoparticles that bind to protein receptors. Filtering the observed TERS spectra
      with the regression model can then selectively image the protein receptor.
      Experiments with mutant proteins suggest that key amino acids provide significant
      contributions to the observed TERS signal, which enables the differentiation of
      protein receptors. These results demonstrate the selectivity that can be obtained
      in TERS images through a controlled plasmonic interaction. This approach has
      further implications for identifying membrane receptors that bind specific
      molecules relevant to drug targeting and chemical signaling. 

PMID- 25759959
TI  - In situ formation of cobalt oxide nanocubanes as efficient oxygen evolution
      catalysts.
AB  - Oxygen evolution from water poses a significant challenge in solar fuel
      production because it requires an efficient catalyst to bridge the one-electron
      photon capture process with the four-electron oxygen evolution reaction (OER).
      Here, a new strategy was developed to synthesize nonsupported ultrasmall cobalt
      oxide nanocubanes through an in situ phase transformation mechanism using a
      layered Co(OH)(OCH3) precursor. Under sonication, the precursor was exfoliated
      and transformed into cobalt oxide nanocubanes in the presence of NaHCO3-Na2SiF6
      buffer solution. The resulting cobalt catalyst with an average particle size less
      than 2 nm exhibited a turnover frequency of 0.023 per second per cobalt in
      photocatalytic water oxidation. X-ray absorption results suggested a unique
      nanocubane structure, where 13 cobalt atoms fully coordinated with oxygen in an
      octahedral arrangement to form 8 Co4O4 cubanes, which may be responsible for the
      exceptionally high OER activity. 

PMID- 25759960
TI  - Quadratic Association Between Corticomotor and Spinal-Reflexive Excitability and
      Self-Reported Disability in Participants With Chronic Ankle Instability.
AB  - CONTEXT: Spinal-reflexive and corticomotor excitability may have a critical role
      in altering muscle function needed to stabilize the ankle in people with chronic
      ankle instability (CAI). OBJECTIVE: To determine the association between self
      reported disability and both spinal-reflexive and corticomotor excitability in
      people with CAI. DESIGN: Descriptive laboratory study. SETTING: Research
      laboratory. PARTICIPANTS: 30 participants with CAI. MAIN OUTCOME MEASURES: Soleus
      spinal-reflexive excitability was measured with normalized Hoffmann reflexes (H:M
      ratio), and corticomotor excitability was measured with transcranial magnetic
      stimulation and quantified by normalized motor-evoked-potential (MEP) amplitudes
      at 120% of active motor threshold (120%MEP). Self-reported disability was
      quantified with the activities-of-daily-living and sport subscales of the Foot
      and Ankle Ability Measure (FAAM-ADL and FAAM-S). Separate linear Pearson product
      moment correlations and nonlinear quadratic correlations were used to determine
      associations between the neural-excitability and disability variables. RESULTS:
      Thirty participants were included in the spinal-reflexive-excitability analysis,
      while only 19 were included in the corticomotor analysis. There was a
      significant, weak linear association between H:M ratio and FAAM-ADL (R = .39, P =
      .03) and a nonsignificant, weak linear association between H:M ratio and FAAM-S
      (R = .36, P = .06). There were significant, moderate quadratic associations
      between H:M ratio and both FAAM-ADL (R = .48, P = .03) and FAAM-S (R = .50, P =
      .02). There was a significant, moderate linear association between 120%MEP and
      FAAM-ADL (R = -.48, P = .04) and a nonsignificant, moderate negative linear
      association between FAAM-S (R = -.42, P = .07). There was a significant, moderate
      quadratic association between 120%MEP and FAAM-ADL (R = .57, P = .046) and a
      significant, strong quadratic correlation between 120%MEP and FAAM-S (R = .71, P
      = .004). CONCLUSIONS: There are significant quadratic associations between self
      reported disability and both spinal-reflexive and corticomotor excitability of
      the soleus. CAI participants with low or high neural excitability present with
      lower function.

PMID- 25759961
TI  - Effect of Zinc Supplementation on GH, IGF1, IGFBP3, OCN, and ALP in Non-Zinc
      Deficient Children.
AB  - OBJECTIVE: Because most publications on growth and development deal with children
      with zinc deficiency, we decided to study the effects of this micronutrient on
      the secretion of growth hormone (GH), insulin-like growth factor 1 (IGF1),
      insulin-like growth factor binding protein 3 (IGFBP3), osteocalcin (OCN), and
      alkaline phosphatase (ALP) in healthy and eutrophic children. This study is
      original because the methodology was unique. METHODS: Forty schoolchildren
      participated in the study, 17 females and 23 males, aged 8 and 9 years. The study
      was carried out during a 3-month period. It was characterized as a triple-blind
      randomized controlled trial. The children were divided in a control group (20
      schoolchildren using 10% sorbitol) and experimental group (20 schoolchildren
      using zinc). All were submitted to oral zinc supplementation (10 mg Zn/day) and
      venous zinc administration (0.06537 mg Zn/kg of body weight). Blood samples were
      collected at 0, 60, 120, 180, and 210 min. All schoolchildren were also submitted
      to anthropometric, clinical, and dietetic assessments as well as biochemistry
      analyses. RESULTS: Oral zinc supplementation in the experimental group (1)
      stimulated an increase in the consumption of protein and fat (p = 0.0007, p <
      0.0001, p < 0.0001, respectively), (2) increased basal serum zinc (p < 0.0001),
      (3) increased plasma ALP (p = 0.0270), and (4) showed a positive correlation for
      IGF1, IGFBP3, and OCN, comparing before and after oral zinc supplementation (p =
      0.0011, p < 0.0001, p < 0.0446, respectively). During zinc administration, plasma
      IGF1 and IGFBP3 increased significantly in the experimental group (p = 0.0468, p
      < 0.0001, respectively). Plasma GH increased in the experimental group but
      without statistical difference comparing before and after oral zinc
      supplementation. CONCLUSIONS: Zinc supplementation stimulated an increase in the
      consumption of some macronutrients and basal serum zinc and improved plasma
      alkaline phosphatase levels. Zinc administration increased hormones of the GH
      IGF1 system.

PMID- 25759962
TI  - Diabetic retinopathy screening and the use of telemedicine.
AB  - PURPOSE OF REVIEW: Evidence-based practice guidelines and treatments are highly
      effective in reducing vision loss from diabetic retinopathy. However, less than
      half of the total number of patients with diabetes mellitus receive recommended
      annual retinal evaluations, and vision loss due to diabetic retinopathy remains
      the leading cause of blindness in adults. Poor adherence to screening
      recommendations stems from a number of challenges which telemedicine technology
      may address to increase the evaluation rates and ultimately reduce vision loss.
      The aim of this review was to provide an update on the recent advances in tele
      ophthalmology and how it may expand our current concept of eye care delivery for
      diabetic eye disease. RECENT FINDINGS: The benefits of telemedicine diabetic
      retinopathy are proven for large population-based systems. Outcomes information
      from community-based programs is now also beginning to emerge. Improved screening
      rates and less vision loss from diabetic retinopathy are being reported after
      implementation of telemedicine programs. New imaging platforms for telemedicine
      programs may enhance the ability to detect and grade diabetic retinopathy.
      However, financial factors remain a barrier to widespread implementation.
      SUMMARY: Telemedicine diabetic retinopathy screening programs may have a
      significant impact on reducing the vision complications and healthcare burden
      from the growing diabetes epidemic.

PMID- 25759963
TI  - Emerging techniques for pathogen discovery in endophthalmitis.
AB  - PURPOSE OF REVIEW: Despite the inability to detect certain organisms and
      relatively low yield, microbial culture is the current gold standard for the
      diagnosis of most intraocular infections. Research on alternative molecular
      diagnostic methods has produced an array of strategies that augment and improve
      pathogen detection. This review summarizes the most recent literature on this
      topic. RECENT FINDINGS: The yield of traditional microbial culture has not
      improved since the Endophthalmitis Vitrectomy Study results were published 20
      years ago. Advances in PCR methods have enabled quantification of pathogen load
      and screening for multiple organisms at once. More recently, deep sequencing
      techniques allow highly sensitive detection of any DNA-based life form in a
      specimen. This offers the promise of not only improved detection of traditional
      organisms but can also identify organisms not previously associated with
      endophthalmitis. SUMMARY: Molecular diagnostic methods enhance the results of
      microbial culture and may become the new standard in the diagnosis of intraocular
      infections.

PMID- 25759964
TI  - Optogenetics.
AB  - PURPOSE OF REVIEW: In this review, we will discuss the recent developments in
      optogenetics and their potential applications in ophthalmology to restore vision
      in retinal degenerative diseases. RECENT FINDINGS: In recent years, we have seen
      major advances in the field of optogenetics, providing us with novel opsins for
      potential applications in the retina. Microbial opsins with improved light
      sensitivity and red-shifted action spectra allow optogenetic stimulation at light
      levels well below the safety threshold in the human eye. In parallel, remarkable
      success in the development of highly efficient viral vectors for ocular gene
      therapy led to new strategies of using these novel optogenetic tools for vision
      restoration. SUMMARY: These recent findings show that novel optogenetic tools and
      viral vectors for ocular gene delivery are now available providing many
      opportunities to develop potential optogenetic strategies for vision restoration.

PMID- 25759965
TI  - Advances in drug delivery to the posterior segment.
AB  - PURPOSE OF REVIEW: Emerging developments and research for drug delivery to the
      posterior segment offer a promising future for the treatment of vitreoretinal
      disease. As new technologies enter the market, clinicians should be aware of new
      indications and ongoing clinical trials. RECENT FINDINGS: This review summarizes
      the advantages and shortcomings of the most commonly used drug delivery methods,
      including vitreous dynamics, physician sustainability and patient preferences.
      Currently available, intravitreal, corticosteroid-release devices offer surgical
      and in-office management of retinal vascular disease and posterior uveitis. The
      suprachoroidal space offers a new anatomic location for the delivery of lower
      dose medications directly to the target tissue. Implantable drug reservoirs would
      potentially allow for less frequent intravitreal injections reducing treatment
      burdens and associated risks. Newer innovations in encapsulated cell technology
      offer promising results in early clinical trials. SUMMARY: Although pars plana
      intravitreal injection remains the mainstay of therapy for many vitreoretinal
      diseases, targeted delivery and implantable eluting devices are rapidly
      demonstrating safety and efficacy. These therapeutic modalities offer promising
      options for the vitreoretinal therapeutic landscape.

PMID- 25759966
TI  - Effect of Public Reporting on MR Imaging Use for Low Back Pain.
AB  - PURPOSE: To determine whether magnetic resonance (MR) imaging examination rates
      for low back pain before conservative therapy in the Medicare and privately
      insured populations changed after introduction of a Centers for Medicare &
      Medicaid Services public reporting initiative. MATERIALS AND METHODS:
      Institutional review board approval was obtained, with waiver of informed
      consent. A retrospective study was performed by using fee-for-service claims data
      from Medicare and a commercial carrier (Blue Cross Blue Shield of Texas [BCBSTX])
      for Texas enrollees. OP-8 was calculated, which is a publicly reported measure as
      of 2009 of the proportion of MR imaging examinations performed for low back pain
      without history of conservative therapy. For 330 463 MR imaging examinations, OP
      8 rates, trends, and regional variation were analyzed for 2008-2011 within
      different outpatient settings-outpatient hospital department (OHD) and
      nonhospital outpatient department (NOD)-according to payer. Largest-volume
      hospitals were also evaluated within the Medicare population. RESULTS: No
      significant reduction was found in annual OP-8 values for Medicare or BCBSTX
      (Medicare OHD, 0.35 for 2008 vs 0.36 for 2009 [P = .01]; BCBSTX OHD, 0.42 for
      2008 vs 0.44 for 2009 [P = .03]; Medicare NOD, 0.33 for 2008 vs 0.35 for 2009 [P
      < .0001]; and BCBSTX NOD, 0.43 for 2008 vs 0.42 for 2009[P = .23]). These changes
      were not sustained during subsequent years in the BCBSTX population, and there
      were no further changes in Medicare rates. Among hospitals with highest Medicare
      volumes, those with the highest OP-8 rates in 2008 were associated with the
      highest decrease in their measure. (The annual change rate was negative for all
      years, with 2008 as the reference [P < .0001 for 2009-2011].) Hospitals with the
      lowest OP-8 rates had increases in OP-8 rates, which persisted in following years
      (P = .006 for 2009, P = .037 for 2010, and P = .004 for 2011). Hospitals with
      baseline OP-8 rates in the 25th-75th percentile remained relatively steady over
      time. CONCLUSION: No evidence was found that public reporting (OP-8) reduced MR
      imaging rates for low back pain without conservative therapy in either Medicare
      or commercially insured populations in hospital or nonhospital settings.

PMID- 25759967
TI  - Accuracy of CT for Selecting Candidates for Coronary Artery Bypass Graft Surgery:
      Combination with the SYNTAX Score.
AB  - PURPOSE: To investigate the diagnostic performance of coronary computed
      tomographic (CT) angiography for selecting candidates for coronary artery bypass
      graft (CABG) surgery according to the 2011 American College of Cardiology
      Foundation (ACCF) and American Heart Association (AHA) guidelines for CABG
      surgery and determine the added value of SYNTAX (Synergy between PCI with TAXUS
      and Cardiac Surgery) scoring for selecting CABG surgery candidates. MATERIALS AND
      METHODS: Approval was obtained from the Institutional Review Board, and informed
      consent was waived for this retrospective study. A total of 399 patients (mean
      age, 63.8 years; 244 men and 155 women) who underwent both coronary CT
      angiography and invasive coronary angiography were included. Eligible criteria
      for CABG surgery were established on the basis of the 2011 ACCF/AHA guidelines.
      RESULTS: from coronary CT angiography and invasive coronary angiography were
      retrospectively reviewed, and SYNTAX scores were determined. The diagnostic
      performance of coronary CT angiography for selecting CABG surgery candidates was
      calculated with invasive coronary angiography as the reference method. The
      diagnostic performance of coronary CT angiography alone, the CT-based SYNTAX
      score, and the combined coronary CT angiography with CT-based SYNTAX score were
      assessed by using a combination of invasive coronary angiography and invasive
      coronary angiography-based SYNTAX scores as a reference method. Statistical
      analyses were performed by using the generalized estimating equation, independent
      t test, Mann-Whitney U test, Wilcoxon signed rank test, Fisher exact test, and
      chi(2) statistics. RESULTS: The overall sensitivity, specificity, positive
      predictive value (PPV), and negative predictive value of coronary CT angiography
      for selecting CABG surgery candidates were 96.5%, 96.5%, 88.3%, and 99.0%,
      respectively. When a combination of invasive coronary angiography with an
      invasive coronary angiography-based SYNTAX score was used as a standard
      reference, combined coronary CT angiography with a CT-based SYNTAX score had
      higher specificity and PPV (98.3% and 86.0%, respectively) than did coronary CT
      angiography alone (84.5% and 40.4%, respectively; P < .0001). CONCLUSION:
      Coronary CT angiography had diagnostic accuracy comparable to that of invasive
      coronary angiography for selecting CABG surgery candidates, and combining a CT
      based SYNTAX score with coronary CT angiography can be a highly specific method
      for selecting CABG surgery candidates.

PMID- 25759968
TI  - Prognostic Value of Cervical Nodal Necrosis in Nasopharyngeal Carcinoma: Analysis
      of 1800 Patients with Positive Cervical Nodal Metastasis at MR Imaging.
AB  - PURPOSE: To evaluate the prognostic value of cervical nodal necrosis (CNN) in
      patients with nasopharyngeal carcinoma (NPC) with magnetic resonance (MR)
      imaging. MATERIALS AND METHODS: This was an institutional review board-approved
      retrospective study of 1800 patients with newly diagnosed stage T1, 4N1, 3M0 NPC
      who were treated with definitive radiation therapy, with or without chemotherapy,
      between January 2007 and December 2009; the requirement to obtain informed
      consent was waived. MR images were reviewed to assess lymph node status, and
      patients were divided into CNN and non-CNN groups. The overall survival, disease
      free survival, regional relapse-free survival (RRFS), and distant metastasis-free
      survival (DMFS) were calculated with the Kaplan-Meier method, and differences
      were compared by using the log-rank test. RESULTS: The incidence of CNN was 44.0%
      (792 of 1800). After the median follow-up period of 53 months, the 5-year overall
      survival, disease-free survival, RRFS, and DMFS rates of the CNN and non-CNN
      groups were 78.8% and 91.8%, 78.2% and 91.2%, 78.6% and 91.8%, and 78.4% and
      91.6%, respectively (for all rates, P < .001). The distant metastasis rate was
      18.7% (148 of 792) for the CNN group versus 4.6% (46 of 1008) for the non-CNN
      group (P < .01). Subgroup analysis revealed similar survival outcomes between
      stage N1 disease with CNN and stage N2 disease without CNN, stage N2 disease with
      CNN, and stage N3 disease regardless of CNN. CNN, T stage, N stage, age older
      than 44 years, and male sex were significant independent negative prognostic
      factors for overall survival, disease-free survival, RRFS, and DMFS. CONCLUSION:
      CNN is an independent negative prognostic factor in patients with NPC, and it may
      be appropriate to investigate whether N stage should be upgraded by one level in
      patients with CNN.

PMID- 25759969
TI  - Advanced Cirrhosis Combined with Portal Vein Thrombosis: A Randomized Trial of
      TIPS versus Endoscopic Band Ligation Plus Propranolol for the Prevention of
      Recurrent Esophageal Variceal Bleeding.
AB  - PURPOSE: To compare transjugular intrahepatic portosystemic shunt (TIPS)
      placement with or without variceal embolization with endoscopic band ligation
      (EBL) plus propranolol in preventing recurrent esophageal variceal bleeding in
      patients with advanced cirrhosis and portal vein thrombosis. MATERIALS AND
      METHODS: The present randomized controlled trial was approved by the ethics
      committee board of West China Hospital. Written informed consent was obtained
      from each patient. Between January 2010 and December 2012, 73 patients were
      randomly allocated to receive TIPS (n = 37) or EBL plus propranolol (n = 36). The
      comparisons of recurrent variceal bleeding, hepatic encephalopathy, and survival
      rates were based on the Kaplan-Meier method and were compared using the log-rank
      test. RESULTS: The mean follow-up time was 22.8 months +/- 7.7(standard
      deviation) in the TIPS group and 20.9 months +/- 8.9 in the EBL group. The 2-year
      probability of remaining free of recurrent variceal bleeding was higher in the
      TIPS group (77.8%) than in the EBL group (42.9%) (P = .002). Overall
      recanalization was achieved in 24 (64.9%) patients from the TIPS group and seven
      (19.4%) patients from the EBL group. The hepatic encephalopathy rates exhibited
      no significant differences between the two groups (P = .53). The 1- and 2-year
      probability of survival was 86.5% and 72.9%, respectively, in the TIPS group and
      83.3% and 57.2%, respectively, in the EBL group, with no significant difference
      (P = .23). CONCLUSION: TIPS was more effective than EBL plus propranolol in
      preventing recurrent esophageal variceal bleeding in patients with advanced
      cirrhosis and portal vein thrombosis and did not increase the incidence of
      hepatic encephalopathy. Survival was similar in both groups.

PMID- 25759970
TI  - Perianal Sepsis in Hematologic Malignancy: MR Imaging Appearances and Distinction
      from Cryptoglandular Infection in Immunocompetent Patients.
AB  - PURPOSE: To use magnetic resonance (MR) imaging to document the appearance of
      perianal infection in patients with a hematologic malignancy (HM) compared with
      that in immunocompetent control patients. MATERIALS AND METHODS: After an ethical
      waiver was obtained, 38 patients with an HM were matched by age and sex to 38
      control patients with no history of immunocompromise or Crohn disease. Both
      groups had undergone MR imaging for perianal symptoms and/or systemic sepsis. Two
      radiologists who were blinded to the diagnosis independently reviewed the MR
      images and recorded the size and distribution of abscesses and/or fistula tracts,
      the extent of perianal edema, and the likely diagnosis. Groups were compared by
      using the Mann-Whitney-Wilcoxon, chi(2), or Fisher exact test. Receiver operating
      characteristic (ROC) curves were constructed to estimate the ability of MR
      imaging to help distinguish patients with an HM from control patients. RESULTS:
      Patients with an HM had significantly greater perianal edema than did control
      patients (mean arc angle of anal canal involved, 220 degrees  vs 60 degrees ; P <
      .001). However, they had significantly lower rates of fistula (15 [39.5%] vs 35
      [92.1%] of 38; P < .001). Abscesses were similar in frequency (10 [26.3%] vs 17
      [44.7%] of 38; P = .15) and were unrelated to the degree of neutropenia (P = .71)
      or the use of chemotherapy (P = .10). Surgical treatment was rarely required in
      patients with an HM, either during the acute illness (four [10.5%] of 38) or
      thereafter (three [7.9%] of 38). MR imaging had an excellent ability to help
      discriminate patients with HM from immunocompetent patients (areas under the ROC
      curve, 0.91 and 0.97). CONCLUSION: Perianal infection in patients with an HM is
      more likely to cause diffuse perianal edema and is less likely to cause fistulas
      than in immunocompetent patients. MR imaging can help distinguish patients with
      an HM from those without immunocompromise.

PMID- 25759971
TI  - Comparison of Quantitative Cartilage T2 Measurements and Qualitative MR Imaging
      between Professional Ballet Dancers and Healthy Volunteers.
AB  - PURPOSE: To compare qualitative magnetic resonance (MR) images and quantitative
      T2 measurements of the tibiotalar cartilage between ballerinas and healthy
      volunteers. MATERIALS AND METHODS: Institutional review board approval for this
      study and informed consent (from all participants) were obtained. MR examinations
      were performed by using a 3-T MR imaging system with 21 professional female
      ballet dancers and 20 healthy female volunteers. Two musculoskeletal radiologists
      qualitatively measured tibiotalar cartilage T2 values in the anterior zones,
      middle zones, and posterior zones of cartilage. MR findings were also
      qualitatively analyzed in both groups. RESULTS: The tibial cartilage T2 values
      measured in the anterior and posterior zones and the talar cartilage T2 values
      measured in all three zones were significantly higher in the ballerina group than
      in the control group (P < .001). The posterior zones exhibited the highest T2
      values among the three tibiotalar cartilage zones in both groups (P < .001). A
      significant between-group difference was evident in terms of the presence of
      posterior soft-tissue edema (P = .001) and flexor hallucis longus tenosynovitis
      (P < .001). CONCLUSION: The findings showed a trend toward increasing cartilage
      T2 values in ballerinas when compared with control subjects, indicating that
      quantitative T2 measurement may potentially be used as a noninvasive imaging tool
      for early detection of cartilage lesions in the tibiotalar joint.

PMID- 25759972
TI  - Association of Coronary Artery Calcification and Mortality in the National Lung
      Screening Trial: A Comparison of Three Scoring Methods.
AB  - PURPOSE: To evaluate three coronary artery calcification (CAC) scoring methods to
      assess risk of coronary heart disease (CHD) death and all-cause mortality in
      National Lung Screening Trial (NLST) participants across levels of CAC scores.
      MATERIALS AND METHODS: The NLST was approved by the institutional review board at
      each participating institution, and informed consent was obtained from all
      participants. Image review was HIPAA compliant. Five cardiothoracic radiologists
      evaluated 1575 low-dose computed tomographic (CT) scans from three groups: 210
      CHD deaths, 315 deaths not from CHD, and 1050 participants who were alive at
      conclusion of the trial. Radiologists used three scoring methods: overall visual
      assessment, segmented vessel-specific scoring, and Agatston scoring. Weighted Cox
      proportional hazards models were fit to evaluate the association between scoring
      methods and outcomes. RESULTS: In multivariate analysis of time to CHD death,
      Agatston scores of 1-100, 101-1000, and greater than 1000 (reference category 0)
      were associated with hazard ratios of 1.27 (95% confidence interval: 0.69, 2.53),
      3.57 (95% confidence interval: 2.14, 7.48), and 6.63 (95% confidence interval:
      3.57, 14.97), respectively; hazard ratios for summed segmented vessel-specific
      scores of 1-5, 6-11, and 12-30 (reference category 0) were 1.72 (95% confidence
      interval: 1.05, 3.34), 5.11 (95% confidence interval: 2.92, 10.94), and 6.10 (95%
      confidence interval: 3.19, 14.05), respectively; and hazard ratios for overall
      visual assessment of mild, moderate, or heavy (reference category none) were 2.09
      (95% confidence interval: 1.30, 4.16), 3.86 (95% confidence interval: 2.02,
      8.20), and 6.95 (95% confidence interval: 3.73, 15.67), respectively. CONCLUSION:
      By using low-dose CT performed for lung cancer screening in older, heavy smokers,
      a simple visual assessment of CAC can be generated for risk assessment of CHD
      death and all-cause mortality, which is comparable to Agatston scoring and
      strongly associated with outcome.

PMID- 25759973
TI  - Aggregation features and fluorescence of Hoechst 33258.
AB  - The functionality of the bisbenzimide Hoechst 33258 in solution has been largely
      exploited in the quantification of DNA. Understanding of its behavior is
      essential to promote its widespread application and learning of biological
      processes. A detailed study of the dimerization process of the fluorescent blue
      dye Hoechst 33258 is carried out by isothermal titration calorimetry, absorbance,
      fluorescence, differential scanning calorimetry and T-jump kinetic measurements.
      The dimer/monomer ratio depends on the dye concentration and the ionic strength.
      The dimerization constant determined under physiological conditions (pH = 7.0; I
      = 0.10 M), KD = 3 * 10(4) M(-1), conveys that only micromolar concentrations of
      the dye can ensure reasonably high amounts of the monomer species in solution.
      For instance, for 10 MUM dye content, the dimer prevails for I > 0.08 M, whereas
      the monomer is observed at low ionic strength, a key issue to be elucidated as
      long as the dimer species is more fluorescent than the monomer and the
      fluorescence intensity strongly relies on the ionic strength and the dye
      concentration. 

PMID- 25759974
TI  - The histopathologic features of Integra(r) Dermal Regeneration Template.

PMID- 25759975
TI  - Effect of a protein-free diet in the development of food allergy and oral
      tolerance in BALB/c mice.
AB  - The aim of the present study was to investigate the effect of a protein-free diet
      in the induction of food allergy and oral tolerance in BALB/c mice. The
      experimental model used was mice that were fed, since weaning up to adulthood, a
      balanced diet in which all dietary proteins were replaced by amino acid diet
      (Aa). The absence of dietary proteins did not prevent the development of food
      allergy to ovalbumin (OVA) in these mice. However, Aa-fed mice produced lower
      levels of IgE, secretory IgA and cytokines. In addition, when compared with mice
      from control group, Aa-fed mice had a milder aversive reaction to the allergen
      measured by consumption of OVA-containing solution and weight loss during food
      allergy development. In addition, mice that did not have dietary proteins in
      their diets were less susceptible to induction of oral tolerance. One single oral
      administration was not enough to suppress specific serum Ig and IgG1 levels in
      the Aa-fed group, although it was efficient to induce suppression in the control
      group. The present results indicate that the stimulation by dietary proteins
      alters both inflammatory reactivity and regulatory immune reactivity in mice
      probably due to their effect in the maturation of the immune system.

PMID- 25759976
TI  - Tunable porosities and shapes of fullerene-like spheres.
AB  - The formation of reversible switchable nanostructures monitored by solution and
      solid-state methods is still a challenge in supramolecular chemistry. By a
      comprehensive solid state and solution study we demonstrate the potential of the
      fivefold symmetrical building block of pentaphosphaferrocene in combination with
      Cu(I) halides to switch between spheres of different porosity and shape. With
      increasing amount of CuX, the structures of the formed supramolecules change from
      incomplete to complete spherically shaped fullerene-like assemblies possessing an
      Ih -C80 topology at one side and to a tetrahedral-structured aggregate at the
      other. In the solid state, the formed nano-sized aggregates reach an outer
      diameter of 3.14 and 3.56 nm, respectively. This feature is used to reversibly
      encapsulate and release guest molecules in solution. 

PMID- 25759977
TI  - The contribution of the acetabular labrum to hip joint stability: a quantitative
      analysis using a dynamic three-dimensional robot model.
AB  - The acetabular labrum provides mechanical stability to the hip joint in extreme
      positions where the femoral head is disposed to subluxation. We aimed to quantify
      the isolated labrum's stabilizing value. Five human cadaveric hips were mounted
      to a robotic manipulator, and subluxation potential tests were run with and
      without labrum. Three-dimensional (3D) kinematic data were quantified using the
      stability index (Colbrunn et al., 2013, "Impingement and Stability of Total Hip
      Arthroplasty Versus Femoral Head Resurfacing Using a Cadaveric Robotics Model,"
      J. Orthop. Res., 31(7), pp. 1108-1115). Global and regional stability indices
      were significantly greater with labrum intact than after total labrectomy for
      both anterior and posterior provocative positions. In extreme positions, the
      labrum imparts significant overall mechanical resistance to hip subluxation.
      Regional stability contributions vary with joint orientation. 

PMID- 25759980
TI  - Only health insurances are interested.

PMID- 25759978
TI  - Inflammatory bowel disease in pediatric patients: Characteristics of newly
      diagnosed patients from the CEDATA-GPGE Registry.
AB  - BACKGROUND: Inflammatory bowel disease (IBD) can arise at any age, with peak
      incidence in adolescence and young adulthood. A registry of pediatric cases of
      IBD offers the opportunity to document their diagnosis and treatment, with the
      ultimate aim of improving diagnosis and treatment in the future. METHODS: In the
      German-language CEDATA-GPGE registry, 3991 cases of IBD in patients less than 18
      years of age were documented from 2004 to 2014. The 1257 patients who were
      prospectively included in the registry upon diagnosis and whose further course
      was documented for at least three months were analyzed in two separate groups-
      under 10 years old, and 10 years and above--with respect to the type and duration
      of their symptoms until diagnosis, the completeness of the diagnostic evaluation,
      the disease phenotype, and the initial treatment. RESULTS: Of the 958 patients
      for whom full documentation was available, 616 (64.3%) had Crohn's disease (CD),
      278 (29%) had ulcerative colitis (UC), 64 (6.7%) had an unclassified IBD, and
      23.2% were under 10 years old. The latency to diagnosis was longer for CD than
      for UC (0.5 versus 0.3 years), regardless of age. 62.5% of the CD patients had
      ileocolonic involvement, and more than half had involvement of the upper
      gastrointestinal tract. 71% of the patients with UC had subtotal colitis or
      pancolitis. Continuous improvement was seen in diagnostic assessment according to
      published guidelines. For example, in 2004/2005, 69% of patients were evaluated
      endoscopically with ileocolonoscopy and esophagogastroduodenoscopy; this fraction
      had risen to nearly 100% by 2013/2014. Similarly, the percentage of patients who
      underwent a diagnostic evaluation of the small intestine, as recommended, rose
      from 41.2% to 60.9% over the same period. The most common initial treatments were
      5- amino - salicylates (86.8% CD, 100% UC) and glucocorticoids (60.6% CD, 65.6%
      UC). 32% of the patients with CD received exclusive enteral nutrition therapy.
      CONCLUSION: Most of these pediatric patients with IBD, whether in the younger or
      the older age group, had extensive bowel involvement at the time of diagnosis.
      The registry data imply that improvement in clinical course may be achieved by
      shortening the time to diagnosis and by closer adherence to the diagnostic and
      therapeutic guidelines.

PMID- 25759979
TI  - IgG4-related autoimmune diseases: Polymorphous presentation complicates diagnosis
      and treatment.
AB  - BACKGROUND: IgG4-associated autoimmune diseases are systemic diseases affecting
      multiple organs of the body. Autoimmune pancreatitis, with a prevalence of 2.2
      per 100,000 people, is one such disease. Because these multi-organ diseases
      present in highly variable ways, they were long thought just to affect individual
      organ systems. This only underscores the importance of familiarity with these
      diseases for routine clinical practice. METHODS: This review is based on
      pertinent articles retrieved by a selective search in PubMed, and on the
      published conclusions of international consensus conferences. RESULTS: The
      current scientific understanding of this group of diseases is based largely on
      case reports and small case series; there have not been any randomized controlled
      trials (RCTs) to date. Any organ system can be affected, including (for example)
      the biliary pathways, salivary glands, kidneys, lymph nodes, thyroid gland, and
      blood vessels. Macroscopically, these diseases cause diffuse organ swelling and
      the formation of pseudotumorous masses. Histopathologically, they are
      characterized by a lymphoplasmacytic infiltrate with IgG4-positive plasma cells,
      which leads via an autoimmune mechanism to the typical histologic findings-
      storiform fibrosis ("storiform" = whorled, like a straw mat) and obliterative,
      i.e., vessel-occluding, phlebitis. A mixed Th1 and Th2 immune response seems to
      play an important role in pathogenesis, while the role of IgG4 antibodies, which
      are not pathogenic in themselves, is still unclear. Glucocorticoid treatment
      leads to remission in 98% of cases and is usually continued for 12 months as
      maintenance therapy. Most patients undergo remission even if untreated. Steroid
      resistant disease can be treated with immune modulators. CONCLUSION: IgG4
      associated autoimmune diseases are becoming more common, but adequate,
      systematically obtained data are now available only from certain Asian countries.
      Interdisciplinary collaboration is a prerequisite to proper diagnosis and
      treatment. Treatment algorithms and RCTs are needed to point the way to organ
      specific treatment in the future.

PMID- 25759981
TI  - In reply.

PMID- 25759982
TI  - Upregulation of microRNA-126-5p is associated with drug resistance to cytarabine
      and poor prognosis in AML patients.
AB  - MicroRNAs (miRs) have been shown to negatively regulate gene expression by
      binding to mRNAs, and they play an important role in various physiological
      processes and malignancies. A previous study identified mature miR-126-3p as an
      onco-microRNA that is generated from the pre-microRNA, miR-126. Although miR-126
      also generates mature miR-126-5p, its function is less clear. In the present
      study, the relationship between miR-126-5p/3p expression levels and overall
      survival in 109 patients with acute myeloid leukemia (AML) who received intensive
      therapy were evaluated. Higher expression levels above the median value of miR
      126-5p/3p were correlated with a poorer overall survival. The hazard ratio and
      95% confidence intervals (95% CI) for the higher expression group relative to the
      lower expression group of miR-126-5p/3p were 2.098 (95% CI: 1.075-4.228) and
      1.958 (95% CI: 1.001-3.927), respectively. An interaction was not observed
      between the hazard ratios of miR-126-5p and miR-126-3p (p=0.73). Transfection of
      the mimic miR-126-5p into the AML cell line, KG-1, resulted in a decrease in the
      sensitivity to cytarabin and the expression level of Klotho mRNA as well as the
      elevation in the phosphorylation of Akt. The results of the present study
      demonstrated that higher expression levels of miR-126-5p/3p in patients with AML
      resulted in a poorer prognosis. Furthermore, miR-126-5p elevated the
      phosphorylation of Akt.

PMID- 25759983
TI  - Toward the discovery of dual inhibitors for botulinum neurotoxin A: concomitant
      targeting of endocytosis and light chain protease activity.
AB  - Dyngo-4aTM has been found to be an endocytic inhibitor of BoNT/A neurotoxicity
      through dynamin inhibition. Herein, we demonstrate this molecule to have a
      previously unrecognized dual activity against BoNT/A, dynamin-protease
      inhibition. To establish the importance of this dual activity, detailed kinetic
      analysis of Dyngo-4a's inhibition of BoNT/A metalloprotease as well as cellular
      and animal toxicity studies have been described. The research presented is the
      first polypharmacological approach to counteract BoNT/A intoxication. 

PMID- 25759985
TI  - Ancestral experience as a game changer in stress vulnerability and disease
      outcomes.
AB  - Stress is one of the most powerful experiences to influence health and disease.
      Through epigenetic mechanisms, stress may generate a footprint that propagates to
      subsequent generations. Programming by prenatal stress or adverse experience in
      parents, grandparents, or earlier generations may thus be a critical determinant
      of lifetime health trajectories. Changes in regulation of microRNAs (miRNAs) by
      stress may enhance the vulnerability to certain pathogenic factors. This review
      explores the hypothesis that miRNAs represent stress-responsive elements in
      epigenetic regulation that are potentially heritable. Recent findings suggest
      that miRNAs are key players linking adverse early environments or ancestral
      stress with disease risk, thus they represent useful predictive disease
      biomarkers. Since miRNA signatures of disease are potentially heritable, big data
      management platforms will be vital to harness multi-generational information and
      capture succinct yet potent biomarkers capable of directing preventative
      treatments. This feature would offer a unique window of opportunity to advance
      personalized medicine. 

PMID- 25759984
TI  - Dicaine represses apoptosis-linked gene 2-interacting protein X expression to
      induce airway epithelial barrier dysfunction.
AB  - Epithelial barrier dysfunction is associated with a number of inflammatory
      disorders. However, the pathogenesis of epithelial barrier dysfunction is
      unclear. This study aims to elucidate the involvement of dicaine in airway
      epithelial barrier dysfunction. In the present study, an RPMI2650 (Rpc) human
      airway epithelial cell line was cultured, with or without dicaine, in monolayers
      using Transwells. In order to assess airway epithelial barrier function, the
      levels of transepithelial electrical resistance and permeability to ovalbumin
      (OVA) were measured. Expression of apoptosis-linked gene 2-interacting protein X
      (Alix) in Rpc cells was assessed using quantitative reverse transcription
      polymerase chain reaction and western blotting. The antigenicity of OVA was
      assessed using a T cell proliferation assay. The results of the present study
      demonstrated that Alix expression levels were markedly lower in Rpc cells treated
      with dicaine, compared with those not treated with dicaine. An increase in the
      level of transcellular permeability to OVA was observed in Rpc monolayers
      following treatment with dicaine, compared with that in the Rpc monolayer without
      dicaine treatment. Furthermore, the Rpc monolayer maintained high antigenicity
      and induced antigen specific T cell proliferation. In conclusion, dicaine causes
      a decrease in expression levels of Alix, which resulted in compromise of the Rpc
      cell monolayer epithelial barrier function.

PMID- 25759987
TI  - The shape of things to come.

PMID- 25759986
TI  - Treatment changes among older patients with dementia treated with antipsychotics.
AB  - BACKGROUND: Prescribing practice patterns and factors associated with treatment
      changes in older patients initiating antipsychotic treatment for the behavioral
      and psychological symptoms of dementia is not well known. OBJECTIVES: The
      objective of this study is to study 90-day prescribing practice patterns across
      the three most commonly prescribed antipsychotics. METHODS: This is a
      retrospective study using national data from the US Department of Veterans
      Affairs (VA). The study included patients older than 65 years diagnosed with
      dementia who began outpatient treatment with an antipsychotic medication between
      2005 and 2008. Patients were followed for 90 days from their antipsychotic start.
      The primary event of interest was changing to another psychotropic medication.
      Cumulative incidence of treatment change was determined with antipsychotic
      discontinuation and death as competing risks. Covariate-adjusted hazard ratios
      for treatment change were determined using competing risk regression models.
      RESULTS: During the study period, 15,435 patients initiated an atypical
      antipsychotic; 14,791 started olanzapine, quetiapine, or risperidone. Over half
      (55%) of the patients discontinued index treatment within 90 days, 36% continued,
      3% died while on index treatment, and 6% changed to another psychotropic
      medication. Compared with quetiapine, the adjusted hazard of treatment change was
      higher by 43% (p = 0.005) for olanzapine and by 12% (p = 0.08) for risperidone.
      CONCLUSION: The higher hazard of treatment change with olanzapine suggests
      patients either responded worse to or experienced more adverse events with
      olanzapine compared with quetiapine.

PMID- 25759988
TI  - Use every opportunity to develop your skills, aspiring managers urged.

PMID- 25759989
TI  - Young people get a say on what they think about services.

PMID- 25759991
TI  - Exposing babies to peanuts reduces likelihood of allergies.

PMID- 25759992
TI  - New RCNi website offers nurses news and portfolio options.

PMID- 25759993
TI  - Simple questions can help nurses identify girls at risk of female genital
      mutilation.

PMID- 25759994
TI  - Updated Code stresses nurses' accountability for delegation of tasks to competent
      colleagues.

PMID- 25759995
TI  - Qb test improves diagnosis of attention deficit disorder.

PMID- 25759996
TI  - Hospice's family-centred focus gains 'outstanding' rating from regulator.

PMID- 25760001
TI  - Research essentials.

PMID- 25760003
TI  - Research and commentary. Hospital clowns boost healing through the power of
      laughter.

PMID- 25760004
TI  - Let us focus on what young people want.

PMID- 25760008
TI  - Student voice--Life is precious and we must cherish it.

PMID- 25760009
TI  - Refreshing ways to air opinions.

PMID- 25760010
TI  - Understanding the pathophysiology behind febrile convulsions.
AB  - The most common background to hyperpyrexia and convulsions is immaturity of the
      child's physiological reactions to infection, so an understanding of the
      pathophysiology of pyrexia and febrile convulsions in young children enables
      nurses to take appropriate action. Correct management involves prompt recognition
      of rising temperature, administration of antipyretic medication, use of other
      cooling strategies and careful monitoring. Diagnosis of the underlying cause
      occasionally requires laboratory investigation, if no focus for infection is
      found, most cases being viral. 

PMID- 25760011
TI  - Hub and spoke model for nursing student placements in the UK.
AB  - The quality of clinical placements is an important factor in nurse education and
      depends, partly, on the quality of the mentoring. In a hub and spoke model of
      practice learning, pre-qualifying nursing students are allocated to their
      placement (hub) in the traditional way and, in addition, are formally supported
      by their mentor to work in other settings and with different clinicians (spoke
      experiences) for one week in eight. In a first pilot in three children's wards,
      participants reported the wide-ranging benefits of this model, which included: a
      richer learning experience; a heightened sense of belonging; enhanced
      understanding of the patient journey; greater insight into the roles and
      responsibilities of the multiprofessional team; and increased awareness of
      possible career choices. The project's students were able to work more
      confidently with different clinicians and teams, which should help them become
      nurses who deliver high quality, modern health care. 

PMID- 25760012
TI  - Preparation and use of resuscitation equipment to assess and treat children in
      emergency situations.
AB  - This article uses the (A) Airway, (B) Breathing and, (C) Circulation structured
      approach to the assessment of a sick child to provide an overview of the
      equipment used in resuscitation attempts involving children. It emphasises that a
      working knowledge of the resuscitation equipment used in emergency situations is
      fundamental to the process of checking and preparing it. The article is aimed at
      students and newly qualified nurses, but may be also useful as revision for more
      experienced nurses. 

PMID- 25760013
TI  - Observation of excited state proton transfer reactions in 2-phenylphenol and 2
      phenyl-1-naphthol and formation of quinone methide species.
AB  - The excited state intramolecular proton transfer (ESIPT) reactions from a phenol
      (naphthol) to a carbon atom in the adjacent aromatic ring of 2-phenylphenol (1)
      and 2-phenyl-1-naphthol (4) are prototypical examples of intramolecular proton
      transfer not mediated by solvent molecules. Femtosecond time-resolved transient
      absorption (fs-TA) studies are conducted for the first time to directly probe the
      formation of quinone methide (QM) species generated from the ESIPT pathways of 1
      and 4. Steady-state absorption experiments demonstrated 1 exists mainly in its
      non-deprotonated form in neat MeCN and in water-MeCN solutions. Observation of
      the phenolate form in water-containing solution (MeCN-H2O, 1 : 1, v : v) in
      fluorescence spectra demonstrates the occurrence of an ESPT reaction between 1
      and the surrounding water molecules. In neat MeCN a transient species that
      absorbs around 520 nm was detected in fs-TA spectra and was assigned to the QM
      species formed by ESIPT to the 2'-position. This transient signal is strengthened
      in cyclohexane. In a water-MeCN solution, an additional transient species
      assigned to the QM species at the 4'-position of 1 was also detected that absorbs
      around 485 nm. Similar results for 4 were observed, with the absorbance of the
      transient species being more intense, which suggests there is more efficient
      production of the QM species from 4, consistent with quantum yields for deuterium
      exchange in the distal ring reported for these compounds. 

PMID- 25760014
TI  - Fine tunable aqueous solution synthesis of textured flexible SnS2 thin films and
      nanosheets.
AB  - Films and nanosheets of layered chalcogenides are currently under intense
      investigation owing to their application in thin film electronic, optoelectronic,
      and sensor devices. Here, aqueous solution processing of the environmentally
      benign thiostannate, (NH4)4Sn2S6.3H2O, and its subsequent thermal decomposition
      to form continuous highly textured SnS2 thin films are presented. We show how to
      control the film thickness, the coherent scattering domain size, and the
      crystallinity by changes in the processing parameters (i.e. thiostannate
      concentration or angular velocity in the spin coating process). For device
      applications of the semiconducting metal sulfide film it is of interest to
      delaminate the film from the glass substrate to create freestanding nanosheets or
      transfer the film to a flexible polymer substrate. It is shown how metal sulfide
      films can be delaminated from the glass substrate and form large area
      freestanding nanosheets. Furthermore, we extend the delamination process to
      include transfer of the thin film from the glass substrate to a low-cost flexible
      polymer substrate. 

PMID- 25760015
TI  - SP600125 reduces lipopolysaccharide-induced apoptosis and restores the early
      stage differentiation of osteoblasts inhibited by LPS through the MAPK pathway in
      MC3T3-E1 cells.
AB  - Bone degradation is a serious complication of chronic inflammatory diseases such
      as septic arthritis, osteomyelitis, and infected orthopedic implant failure.
      Effective therapeutic treatments for bacteria-caused bone destruction are
      limited. In a previous study, we found that lipopolysaccharide (LPS) induced
      osteoblast apoptosis and inhibited early and late-stage differentiation of
      osteoblasts via activation of the C-Jun N-terminal kinase (JNK) pathway. This
      study aimed to investigate the effect of JNK inhibition by SP600125 on the
      apoptosis and differentiation of MC3T3-E1 osteoblasts suppressed by LPS.
      Following pretreatment with SP600125 for 2 h, MC3T3-E1 cells were treated LPS.
      Following this treatment, cell viability, activity of alkaline phosphatase (ALP)
      and caspase-3 were measured. mRNA and protein expression of osteoblast-specific
      genes, mitogen-activated protein kinases (MAPKs), Bax, Bcl-2 and caspase-3 were
      determined by quantitative polymerase chain reaction (qPCR) and western blot
      analysis. The results showed that SP600125 significantly restored LPS-inhibited
      cell metabolism and ALP activity and reduced the upregulated caspase-3 activity
      of MC3T3-E1 cells induced by LPS. SP600125 also significantly restored the LPS
      suppressed mRNA and protein expression levels of early-stage osteoblast
      associated genes in a dose-dependent manner. SP600125 significantly downregulated
      expression of Bax and caspase-3 but upregulated Bcl-2 expression in MC3T3-E1
      cells stimulated by LPS. Furthermore, SP600125 selectively triggered the MAPK
      pathway by reducing the expression of JNK1, while enhancing the expression of
      extracellular signal-regulated kinase 1 (ERK1). Our results suggested that
      SP600125 reduced LPS-induced osteoblast apoptosis and restored early-stage
      differentiation of osteoblasts inhibited by LPS through MAPK signaling. These
      findings suggest that the therapeutic agent that inhibited JNK1 is of potential
      use for the restoration of osteoblast function in bacteria-induced bone diseases.

PMID- 25760016
TI  - Reduction of hydroxy-functionalised carbaboranyl carboxylic acids and ketones by
      organolithium reagents.
AB  - While the reaction of carbaboranyl carboxylic acids and ketones with
      organolithium reagents generally leads to cleavage of the exo-polyhedral C-C
      bond, introduction of a hydroxyl group at the second carbon atom of the cluster
      enables the reduction of the carbonyl compounds to tertiary alcohols. The
      proposed mechanism involving the formation of dimeric contact ion pairs was
      supported by X-ray crystallography and theoretical calculations. 

PMID- 25760017
TI  - Mechanics of single peptide hydrogelator fibrils.
AB  - The rigidity of peptide fibers is essential for their chemical and biological
      functions, despite that it remains largely unexplored. Here, we present the first
      direct measurement of the mechanics of individual fibers in peptide hydrogels by
      AFM imaging and statistical analysis and find that the intermolecular
      interactions play a considerable role. 

PMID- 25760018
TI  - Identification of Bacterial DNA in the Peripheral Blood of Patients With Active
      Psoriasis.

PMID- 25760019
TI  - Comparison of administrative/billing data to expected protocol-mandated
      chemotherapy exposure in children with acute myeloid leukemia: A report from the
      Children's Oncology Group.
AB  - BACKGROUND: Recently investigators have used analysis of administrative/billing
      datasets to answer clinical and pharmacoepidemiology questions in pediatric
      oncology. However, the accuracy of pharmacy data from administrative/billing
      datasets have not yet been evaluated. The primary objective of this study was to
      determine the concordance of Pediatric Health Information System (PHIS)
      administrative/billing chemotherapy data with Children's Oncology Group (COG)
      protocol-mandated chemotherapy and to assess the implications of this level of
      concordance for further PHIS research. PROCEDURE: Data from 384 pediatric
      patients (1,060 courses of chemotherapy) with acute myeloid leukemia treated on
      COG clinical trial AAML0531 were previously merged with PHIS data. PHIS
      chemotherapy administrative/billing data were reviewed for the first three
      courses of chemotherapy. Accuracy was assessed using three metrics:
      recognizability of chemotherapy pattern by course, chemotherapy administration
      pattern by individual medication, and concordance with the number of days of
      protocol-defined chemotherapy. RESULTS: The chemotherapy pattern was recognizable
      in 87.3% of courses when course-wide accuracy was assessed. Chemotherapy
      administration pattern varied by medication. Cytarabine had perfect concordance
      70.9% of the time, daunorubicin had perfect concordance 77.4% of the time, and
      etoposide had perfect concordance 67.8% of the time. CONCLUSIONS: The accuracy of
      chemotherapy administrative/billing data supports the continued use of PHIS data
      for epidemiology studies as long as investigators perform data quality control
      checks and evaluate each specific medication prior to undertaking definitive
      analyses.

PMID- 25760020
TI  - Interleukin-1beta induced nuclear factor-kappaB binds to a disintegrin-like and
      metalloproteinase with thrombospondin type 1 motif 9 promoter in human
      chondrosarcoma cells.
AB  - Nuclear factor-kappaB (NF-kappaB) is involved in the regulation of inflammation
      associated genes. NF-kappaB forms dimers which bind with sequences referred to as
      NF-kappaB sites (9-11 bp). A disintegrin-like and metalloproteinase with
      thrombospondin type 1 motif 9 (ADAMTS9) is a type of proteoglycanase, which
      proteolytically cleaves versican and aggrecan. ADAMTS9 is a cytokine-inducible
      gene that contains binding sites for NF-kappaB within its promoter region.
      Interleukin-1beta (IL-1beta) affects cartilage metabolism and is involved in the
      NF-kappaB pathway. It is therefore hypothesized that NF-kappaB binding with
      ADAMTS9 promoters may activate IL-1beta, thereby promoting chondrocytic cell
      growth. In the present study, the OUMS-27 chondrocytic human chondrosarcoma cell
      line was treated with IL-1beta with or without inhibitors of NF-kappaB signaling
      pathways. Chromatin immunoprecipitation (ChIP) and electromobility shift assays
      (EMSA) were conducted order to analyze the binding of NF-kappaB with the ADAMTS9
      promoter region. NF-kappaB-p65 subunit phosphorylation was promoted in IL-1beta
      treated cells, which were not treated with inhibitors of NF-kappaB signaling
      pathways. By contrast, NF-kappaB-p65 subunit phosphorylation was inhibited in
      cells that had been treated with BAY-117085, an NF-kappaB pathway inhibitor. ChIP
      and EMSA assays demonstrated that, following treatment with IL-1beta, NF-kappaB
      p65 bound to elements located at -1177 and -1335 in the ADAMTS9 promoter region,
      in contrast to the untreated samples. The results of the present study suggested
      that NF-kappaB may be involved in IL-1beta-induced activation of ADAMTS9 in human
      chondrocytes.

PMID- 25760021
TI  - Nutritional regulation of root development.
AB  - Mineral nutrients such as nitrogen (N), phosphorus (P), and iron (Fe) are
      essential for plant growth, development, and reproduction. Adequate provision of
      nutrients via the root system impacts greatly on shoot biomass and plant
      productivity and is therefore of crucial importance for agriculture. Nutrients
      are taken up at the root surface in ionic form, which is mediated by specific
      transport proteins. Noteworthy, root tips are able to sense the local and
      internal concentrations of nutrients to adjust growth and developmental
      processes, and ultimately, to increase or decrease the exploratory capacity of
      the root system. Recently, important progress has been achieved in identifying
      the mechanisms of nutrient sensing in wild- and cultivated species, including
      Arabidopsis, bean, maize, rice, lupin as well as in members of the Proteaceae and
      Cyperaceae families, which develop highly sophisticated root clusters as
      adaptations to survive in soils with very low fertility. Major findings include
      identification of transporter proteins and transcription factors regulating
      nutrient sensing, miRNAs as mobile signals and peptides as repressors of lateral
      root development under heterogeneous nutrient supply. Understanding the roles
      played by N, P, and Fe in gene expression and biochemical characterization of
      proteins involved in root developmental responses to homogeneous or heterogeneous
      N and P sources has gained additional interest due to its potential for improving
      fertilizer acquisition efficiency in crops.

PMID- 25760022
TI  - CD9 modulates proliferation of human glioblastoma cells via epidermal growth
      factor receptor signaling.
AB  - The tetraspanin CD9 has previously been shown to be involved in various cellular
      activities, including proliferation and migration. In addition, CD9 has been
      shown to be associated with epidermal growth factor receptor (EGFR). A common
      characteristic of glioblastoma multiforme histology is EGFR amplification, which
      affects signal transduction processes. The anti-proliferative effects of CD9 have
      been linked to EGFR signaling pathways, including phosphorylation of
      phosphoinositide-3-kinase (PI3K)/Akt and activation of mitogen-activated protein
      kinase (MAPK)/extracellular signal-regulated protein kinase (Erk). The present
      study demonstrated that CD9 decreased the phosphorylation of EGFR at specific
      sites. In addition, CD9 attenuated EGFR signaling of PI3K/Akt and MAPK/Erk, which
      was associated with cell growth and proliferation. Conversely, small hairpin RNA
      mediated knockdown of CD9 expression enhanced the activation of EGFR signal
      transduction pathways, including PI3K/Akt and MAPK/Erk. These results suggested
      that the mechanism underlying CD9-induced suppression of cell proliferation may
      involve the inhibition of phosphorylation of EGFR and the activity of PI3K/Akt
      and MAPK/Erk signaling pathways.

PMID- 25760023
TI  - Propofol inhibits burn injury-induced hyperpermeability through an apoptotic
      signal pathway in microvascular endothelial cells.
AB  - Recent studies have revealed that an intrinsic apoptotic signaling cascade is
      involved in vascular hyperpermeability and endothelial barrier dysfunction.
      Propofol (2,6-diisopropylphenol) has also been reported to inhibit apoptotic
      signaling by regulating mitochondrial permeability transition pore (mPTP) opening
      and caspase-3 activation. Here, we investigated whether propofol could alleviate
      burn serum-induced endothelial hyperpermeability through the inhibition of the
      intrinsic apoptotic signaling cascade. Rat lung microvascular endothelial cells
      (RLMVECs) were pretreated with propofol at various concentrations, followed by
      stimulation with burn serum, obtained from burn-injury rats. Monolayer
      permeability was determined by transendothelial electrical resistance.
      Mitochondrial release of cytochrome C was measured by ELISA. Bax and Bcl-2
      expression and mitochondrial release of second mitochondrial-derived activator of
      caspases (smac) were detected by Western blotting. Caspase-3 activity was
      assessed by fluorometric assay; mitochondrial membrane potential (Deltapsim) was
      determined with JC-1 (a potential-sensitive fluorescent dye). Intracellular ATP
      content was assayed using a commercial kit, and reactive oxygen species (ROS)
      were measured by dichlorodihydrofluorescein diacetate (DCFH-DA). Burn serum
      significantly increased monolayer permeability (P<0.05), and this effect could be
      inhibited by propofol (P<0.05). Compared with a sham treatment group, intrinsic
      apoptotic signaling activation - indicated by Bax overexpression, Bcl-2
      downregulation, Deltapsim reduction, decreased intracellular ATP level, increased
      cytosolic cytochrome C and smac, and caspase-3 activation - was observed in the
      vehicle group. Propofol not only attenuated these alterations (P<0.05 for all),
      but also significantly decreased burn-induced ROS production (P<0.05). Propofol
      attenuated burn-induced RLMVEC monolayer hyperpermeability by regulating the
      intrinsic apoptotic signaling pathway.

PMID- 25760024
TI  - Metronomic chemotherapy in the neoadjuvant setting: results of two parallel
      feasibility trials (TraQme and TAME) in patients with HER2+ and HER2- locally
      advanced breast cancer.
AB  - Neoadjuvant chemotherapy has practical and theoretical advantages over adjuvant
      chemotherapy strategy in breast cancer (BC) management. Moreover, metronomic
      delivery has a more favorable toxicity profile. The present study examined the
      feasibility of neoadjuvant metronomic chemotherapy in two cohorts [HER2+ (TraQme)
      and HER2- (TAME)] of locally advanced BC. Twenty patients were prospectively
      enrolled (TraQme, n=9; TAME, n=11). Both cohorts received weekly paclitaxel at
      100 mg/m(2) during 8 weeks followed by weekly doxorubicin at 24 mg/m(2) for 9
      weeks in combination with oral cyclophosphamide at 100 mg/day (fixed dose). The
      HER2+ cohort received weekly trastuzumab. The study was interrupted because of
      safety issues. Thirty-six percent of patients in the TAME cohort and all patients
      from the TraQme cohort had stage III BC. Of note, 33% from the TraQme cohort and
      66% from the TAME cohort displayed hormone receptor positivity in tumor tissue.
      The pathological complete response rates were 55% and 18% among patients enrolled
      in the TraQme and TAME cohorts, respectively. Patients in the TraQme cohort had
      more advanced BC stages at diagnosis, higher-grade pathological classification,
      and more tumors lacking hormone receptor expression, compared to the TAME cohort.
      The toxicity profile was also different. Two patients in the TraQme cohort
      developed pneumonitis, and in the TAME cohort we observed more hematological
      toxicity and hand-foot syndrome. The neoadjuvant metronomic chemotherapy regimen
      evaluated in this trial was highly effective in achieving a tumor response,
      especially in the HER2+ cohort. Pneumonitis was a serious, unexpected adverse
      event observed in this group. Further larger and randomized trials are warranted
      to evaluate the association between metronomic chemotherapy and trastuzumab
      treatment.

PMID- 25760025
TI  - Chronic kidney disease in disadvantaged populations.
AB  - The increased burden of chronic kidney disease (CKD) in disadvantaged populations
      is due to both global factors and population-specific issues. Low socioeconomic
      status and poor access to care contribute to health care disparities and
      exacerbate the negative effects of genetic or biological predisposition.
      Provision of appropriate renal care to these populations requires a two-pronged
      approach: expanding the reach of dialysis through development of low-cost
      alternatives that can be practiced in remote locations, and implementation and
      evaluation of cost-effective prevention strategies. Kidney transplantation should
      be promoted by expansion of deceased donor transplant programs and use of
      inexpensive, generic immunosuppressive drugs. The message of World Kidney Day
      2015 is that a concerted attack against the diseases that lead to end-stage renal
      disease, by increasing community outreach, better education, improved economic
      opportunity, and access to preventive medicine for those at highest risk, could
      end the unacceptable relationship between CKD and disadvantage in these
      communities. 

PMID- 25760026
TI  - Silibinin improves palmitate-induced insulin resistance in C2C12 myotubes by
      attenuating IRS-1/PI3K/Akt pathway inhibition.
AB  - The present study investigated the effect of silibinin, the principal potential
      anti-inflammatory flavonoid contained in silymarin, a mixture of flavonolignans
      extracted from Silybum marianum seeds, on palmitate-induced insulin resistance in
      C2C12 myotubes and its potential molecular mechanisms. Silibinin prevented the
      decrease of insulin-stimulated 2-NBDG (2-[N-(7-nitrobenz-2-oxa-1,3-diazol-4
      yl)amino]-2-deoxy-D-glucose) uptake and the downregulation of glutamate
      transporter type 4 (GLUT4) translocation in C2C12 myotubes induced by palmitate.
      Meanwhile, silibinin suppressed the palmitate-induced decrease of insulin
      stimulated Akt Ser473 phosphorylation, which was reversed by wortmannin, a
      specific inhibitor of phosphatidylinositol-3-kinase (PI3K). We also found that
      palmitate downregulated insulin-stimulated Tyr632 phosphorylation of insulin
      receptor substrate 1 (IRS-1) and up-regulated IRS-1 Ser307 phosphorylation. These
      effects were rebalanced by silibinin. Considering several serine/threonine
      kinases reported to phosphorylate IRS-1 at Ser307, treatment with silibinin
      downregulated the phosphorylation of both c-Jun N-terminal kinase (JNK) and
      nuclear factor-kappaB kinase beta (IKKbeta), which was increased by palmitate in
      C2C12 myotubes mediating inflammatory status, whereas the phosphorylation of PKC
      theta was not significantly modulated by silibinin. Collectively, the results
      indicated that silibinin prevented inhibition of the IRS-1/PI3K/Akt pathway, thus
      ameliorating palmitate-induced insulin resistance in C2C12 myotubes.

PMID- 25760027
TI  - Cell cycle synchronization and BrdU incorporation as a tool to study the possible
      selective elimination of ErbB1 gene in the micronuclei in A549 cells.
AB  - Lung cancer often exhibits molecular changes, such as the overexpression of the
      ErbB1 gene that encodes epidermal growth factor receptor (EGFR). ErbB1
      amplification and mutation are associated with tumor aggressiveness and low
      response to therapy. The aim of the present study was to design a schedule to
      synchronize the cell cycle of A549 cell line (a non-small cell lung cancer) and
      to analyze the possible association between the micronuclei (MNs) and the
      extrusion of ErbB1 gene extra-copies. After double blocking, by the process of
      fetal bovine serum deprivation and vincristine treatment, MNs formation was
      monitored with 5-bromo-2-deoxyuridine (BrdU) incorporation, which is an S-phase
      marker. Statistical analyses allowed us to infer that MNs may arise both in
      mitosis as well as in interphase. The MNs were able to replicate their DNA and
      this process seemed to be non-synchronous with the main cell nuclei. The presence
      of ErbB1 gene in the MNs was evaluated by fluorescent in situ hybridization
      (FISH). ErbB1 sequences were detected in the MNs, but a relation between the MNs
      formation and extrusion of amplified ErbB1 could not be established. The present
      study sought to elucidate the meaning of MNs formation and its association with
      the elimination of oncogenes or other amplified sequences from the tumor cells.

PMID- 25760028
TI  - Voluntary exercise prior to traumatic brain injury alters miRNA expression in the
      injured mouse cerebral cortex.
AB  - MicroRNAs (miRNAs) may be important mediators of the profound molecular and
      cellular changes that occur after traumatic brain injury (TBI). However, the
      changes and possible roles of miRNAs induced by voluntary exercise prior to TBI
      are still not known. In this report, the microarray method was used to
      demonstrate alterations in miRNA expression levels in the cerebral cortex of TBI
      mice that were pretrained on a running wheel (RW). Voluntary RW exercise prior to
      TBI: i) significantly decreased the mortality rate and improved the recovery of
      the righting reflex in TBI mice, and ii) differentially changed the levels of
      several miRNAs, upregulating some and downregulating others. Furthermore, we
      revealed global upregulation of miR-21, miR-92a, and miR-874 and downregulation
      of miR-138, let-7c, and miR-124 expression among the sham-non-runner, TBI-non
      runner, and TBI-runner groups. Quantitative reverse transcription polymerase
      chain reaction data (RT-qPCR) indicated good consistency with the microarray
      results. Our microarray-based analysis of miRNA expression in mice cerebral
      cortex after TBI revealed that some miRNAs such as miR-21, miR-92a, miR-874, miR
      138, let-7c, and miR-124 could be involved in the prevention and protection
      afforded by voluntary exercise in a TBI model.

PMID- 25760029
TI  - Sequence analysis of the 5' third of glycoprotein C gene of South American bovine
      herpesviruses 1 and 5.
AB  - Bovine herpesviruses 1 (BoHV-1) and 5 (BoHV-5) share high genetic and antigenic
      similarities, but exhibit marked differences in tissue tropism and
      neurovirulence. The amino-terminal region of glycoprotein C (gC), which is
      markedly different in each of the viruses, is involved in virus binding to
      cellular receptors and in interactions with the immune system. This study
      investigated the genetic and antigenic differences of the 5' region of the gC (5'
      gC) gene (amino-terminal) of South American BoHV-1 (n=19) and BoHV-5 (n=25)
      isolates. Sequence alignments of 374 nucleotides (104 amino acids) revealed mean
      similarity levels of 97.3 and 94.2% among BoHV-1 gC (gC1), respectively, 96.8 and
      95.6% among BoHV-5 gC (gC5), and 62 and 53.3% between gC1 and gC5. Differences
      included the absence of 40 amino acid residues (27 encompassing predicted linear
      epitopes) scattered throughout 5' gC1 compared to 5' gC5. Virus neutralizing
      assays testing BoHV-1 and BoHV-5 antisera against each isolate revealed a high
      degree of cross-neutralization between the viruses, yet some isolates were
      neutralized at very low titers by heterologous sera, and a few BoHV-5 isolates
      reacted weakly with either sera. The virus neutralization differences observed
      within the same viral species, and more pronounced between BoHV-1 and BoHV-5,
      likely reflect sequence differences in neutralizing epitopes. These results
      demonstrate that the 5' gC region is well conserved within each viral species but
      is divergent between BoHV-1 and BoHV-5, likely contributing to their biological
      and antigenic differences.

PMID- 25760031
TI  - Lithium-cyclo-difluoromethane-1,1-bis(sulfonyl)imide as a stabilizing electrolyte
      additive for improved high voltage applications in lithium-ion batteries.
AB  - Lithium-cyclo-difluoromethane-1,1-bis(sulfonyl)imide (LiDMSI) was evaluated as an
      electrolyte additive in lithium-ion batteries for improved high voltage
      applications. Cycling the cathode at high potentials leads to the electrochemical
      oxidation of the salt to form a cathode electrolyte interphase (CEI) layer on the
      cathode surface. With the addition of 2 wt% of LiDMSI to the 1 M LiPF6 in 1 : 1
      (by wt) EC : DEC electrolyte, the capacity retention and the Coulombic efficiency
      in LiNi1/3Co1/3Mn1/3O2/Li-half-cells as well as in LiNi1/3Co1/3Mn1/3O2/graphite
      full-cells were improved. The cycling results point out the less over-potential
      and resistance at the cathode/electrolyte interface. These improvements are
      studied by SEM, EIS and XPS techniques. 

PMID- 25760030
TI  - Contractile profile of esophageal and gastric fundus strips in experimental
      doxorubicin-induced esophageal atresia.
AB  - Esophageal atresia (EA) is characterized by esophageal and gastric motility
      changes secondary to developmental and postsurgical damage. This study evaluated
      the in vitro contractile profile of the distal esophagus and gastric fundus in an
      experimental model of EA induced by doxorubicin (DOXO). Wistar pregnant rats
      received DOXO 2.2 mg/kg on the 8th and 9th gestational days. On day 21.5, fetuses
      were collected, sacrificed, and divided into groups: control, DOXO without EA
      (DOXO-EA), and DOXO with EA (DOXO+EA). Strips from the distal esophagus and
      gastric fundus were mounted on a wire myograph and isolated organ-bath system,
      respectively, and subjected to increasing concentrations of carbamylcholine
      chloride (carbachol, CCh). The isolated esophagus was also stimulated with
      increasing concentrations of KCl. In esophagus, the concentration-effect curves
      were reduced in response to CCh in the DOXO+EA and DOXO-EA groups compared to the
      control group (P<0.05). The maximum effect values (Emax) for DOXO+EA and DOXO-EA
      were significantly lower than control (P<0.05), but the half-maximal effective
      concentration (EC50) values were not significantly different when the three
      groups were compared (P>0.05). In response to KCl, the distal esophagus samples
      in the three groups were not statistically different with regard to Emax or EC50
      values (P>0.05). No significant difference was noted for EC50 or Emax values in
      fundic strips stimulated with CCh (P>0.05). In conclusion, exposure of dams to
      DOXO during gestation inhibited the contractile behavior of esophageal strips
      from offspring in response to CCh but not KCl, regardless of EA induction. The
      gastric fundus of DOXO-exposed offspring did not have altered contractile
      responsiveness to cholinergic stimulation. 

PMID- 25760032
TI  - Platinum oxoboryl complexes as substrates for the formation of 1:1, 1:2, and 2:1
      Lewis acid-base adducts and 1,2-dipolar additions.
AB  - The oxoboryl complex trans-[(Cy3 P)2 BrPt(B=O)] (2) reacts with the Group 13
      Lewis acids EBr3 (E=Al, Ga, In) to form the 1:1 Lewis acid-base adducts trans
      [(Cy3 P)2 BrPt(B=OEBr3 )] (6-8). This reactivity can be extended by using two
      equivalents of the respective Lewis acid EBr3 (E=Al, Ga) to form the 2:1 Lewis
      acid-base adducts trans-[(Cy3 P)2 (Br3 Al-Br)Pt(B=OAlBr3 )] (18) and trans-[(Cy3
      P)2 (Br3 Ga-Br)Pt(B=OGaBr3 )] (15). Another reactivity pattern was demonstrated
      by coordinating two oxoboryl complexes 2 to InBr3 , forming the 1:2 Lewis acid
      base adduct trans-[{(Cy3 P)2 BrPt(B=O)}2 InBr3 ] (20). It was also possible to
      functionalize the B=O triple bond itself. Trimethylsilylisothiocyanate reacts
      with 2 in a 1,2-dipolar addition to form the boryl complex trans-[(Cy3 P)2
      BrPt{B(NCS)(OSiMe3 )}] (27).

PMID- 25760033
TI  - Golgi phosphoprotein 3 expression predicts poor prognosis in patients with
      prostate cancer undergoing radical prostatectomy.
AB  - Golgi phosphoprotein 3 (GOLPH3) has recently been implicated as an oncogene
      involved in the development of carcinoma in a number of organs. The expression of
      GOLPH3 in prostate cancer (PCa) tissues was investigated in the present study.
      Human PC-3 and LNCaP PCa cell lines were analyzed in order to assess whether
      silencing of GOLPH3 expression affects cell vitality, migration and invasion, in
      vitro. An immunohistochemistry analysis was performed in order to measure the
      expression of GOLPH3 in samples from 117 patients with PCa and from 50 patients
      with benign prostatic hyperplasia (BPH). Associations between GOLPH3 expression
      and clinicopathological parameters, such as overall survival, were assessed.
      GOLPH3 expression was shown to be significantly greater in PCa tissues than in
      BPH tissues. GOLPH3 expression was positively correlated with Gleason score
      (P=0.031), tumor stage (T stage; P=0.020) and lymph node status (P=0.013), in
      patients with PCa. Biochemical recurrence-free survival (serum prostate-specific
      antigen-based) and overall survival, were reduced in patients with GOLPH3
      positive PCa. A multivariate analysis indicated that GOLPH3 expression was an
      independent predictor of biochemical recurrence-free survival [hazard ratio (HR),
      2.943; 95% confidence interval (CI), 1.190-5.521; P=0.028], and of overall
      survival (HR, 4.371; 95% CI, 2.045-7.109; P=0.014). Transfection with GOLPH3
      targeted small interfering RNA reduced the capability of PC-3 and LNCaP cell
      lines to proliferate, migrate and invade in vitro, compared with the controls.
      The level of GOLPH3 expression in radical prostatectomy samples may be useful for
      predicting biochemical recurrence-free survival and overall survival in patients
      with PCa.

PMID- 25760034
TI  - Deciphering the dual effect of lipopolysaccharides from plant pathogenic
      Pectobacterium.
AB  - Lipopolysaccharides (LPS) are a component of the outer cell surface of almost all
      Gram-negative bacteria and play an essential role for bacterial growth and
      survival. Lipopolysaccharides represent typical microbe-associated molecular
      pattern (MAMP) molecules and have been reported to induce defense-related
      responses, including the expression of defense genes and the suppression of the
      hypersensitive response in plants. However, depending on their origin and the
      challenged plant, LPS were shown to have complex and different roles. In this
      study we showed that LPS from plant pathogens Pectobacterium atrosepticum and
      Pectobacterium carotovorum subsp. carotovorum induce common and different
      responses in A. thaliana cells when compared to those induced by LPS from non
      phytopathogens Escherichia coli and Pseudomonas aeruginosa. Among common
      responses to both types of LPS are the transcription of defense genes and their
      ability to limit of cell death induced by Pectobacterium carotovorum subsp
      carotovorum. However, the differential kinetics and amplitude in reactive oxygen
      species (ROS) generation seemed to regulate defense gene transcription and be
      determinant to induce programmed cell death in response to LPS from the plant
      pathogenic Pectobacterium. These data suggest that different signaling pathways
      could be activated by LPS in A. thaliana cells. 

PMID- 25760035
TI  - Comparing different models of the development of verb inflection in early child
      Spanish.
AB  - How children acquire knowledge of verb inflection is a long-standing question in
      language acquisition research. In the present study, we test the predictions of
      some current constructivist and generativist accounts of the development of verb
      inflection by focusing on data from two Spanish-speaking children between the
      ages of 2;0 and 2;6. The constructivist claim that children's early knowledge of
      verb inflection is only partially productive is tested by comparing the average
      number of different inflections per verb in matched samples of child and adult
      speech. The generativist claim that children's early use of verb inflection is
      essentially error-free is tested by investigating the rate at which the children
      made subject-verb agreement errors in different parts of the present tense
      paradigm. Our results show: 1) that, although even adults' use of verb inflection
      in Spanish tends to look somewhat lexically restricted, both children's use of
      verb inflection was significantly less flexible than that of their caregivers,
      and 2) that, although the rate at which the two children produced subject-verb
      agreement errors in their speech was very low, this overall error rate hid a
      consistent pattern of error in which error rates were substantially higher in low
      frequency than in high frequency contexts, and substantially higher for low
      frequency than for high frequency verbs. These results undermine the claim that
      children's use of verb inflection is fully productive from the earliest
      observable stages, and are consistent with the constructivist claim that
      knowledge of verb inflection develops only gradually. 

PMID- 25760036
TI  - Metabolic and tissue-specific regulation of acyl-CoA metabolism.
AB  - Acyl-CoA formation initiates cellular fatty acid metabolism. Acyl-CoAs are
      generated by the ligation of a fatty acid to Coenzyme A mediated by a large
      family of acyl-CoA synthetases (ACS). Conversely, acyl-CoAs can be hydrolyzed by
      a family of acyl-CoA thioesterases (ACOT). Here, we have determined the
      transcriptional regulation of all ACS and ACOT enzymes across tissues and in
      response to metabolic perturbations. We find patterns of coordinated regulation
      within and between these gene families as well as distinct regulation occurring
      in a tissue- and physiologically-dependent manner. Due to observed changes in
      long-chain ACOT mRNA and protein abundance in liver and adipose tissue, we
      determined the consequence of increasing cytosolic long-chain thioesterase
      activity on fatty acid metabolism in these tissues by generating transgenic mice
      overexpressing a hyperactive mutant of Acot7 in the liver or adipose tissue.
      Doubling cytosolic acyl-CoA thioesterase activity failed to protect mice from
      diet-induced obesity, fatty liver or insulin resistance, however, overexpression
      of Acot7 in adipocytes rendered mice cold intolerant. Together, these data
      suggest distinct modes of regulation of the ACS and ACOT enzymes and that these
      enzymes act in a coordinated fashion to control fatty acid metabolism in a tissue
      dependent manner. 

PMID- 25760037
TI  - Future coastal population growth and exposure to sea-level rise and coastal
      flooding--a global assessment.
AB  - Coastal zones are exposed to a range of coastal hazards including sea-level rise
      with its related effects. At the same time, they are more densely populated than
      the hinterland and exhibit higher rates of population growth and urbanisation. As
      this trend is expected to continue into the future, we investigate how coastal
      populations will be affected by such impacts at global and regional scales by the
      years 2030 and 2060. Starting from baseline population estimates for the year
      2000, we assess future population change in the low-elevation coastal zone and
      trends in exposure to 100-year coastal floods based on four different sea-level
      and socio-economic scenarios. Our method accounts for differential growth of
      coastal areas against the land-locked hinterland and for trends of urbanisation
      and expansive urban growth, as currently observed, but does not explicitly
      consider possible displacement or out-migration due to factors such as sea-level
      rise. We combine spatially explicit estimates of the baseline population with
      demographic data in order to derive scenario-driven projections of coastal
      population development. Our scenarios show that the number of people living in
      the low-elevation coastal zone, as well as the number of people exposed to
      flooding from 1-in-100 year storm surge events, is highest in Asia. China, India,
      Bangladesh, Indonesia and Viet Nam are estimated to have the highest total
      coastal population exposure in the baseline year and this ranking is expected to
      remain largely unchanged in the future. However, Africa is expected to experience
      the highest rates of population growth and urbanisation in the coastal zone,
      particularly in Egypt and sub-Saharan countries in Western and Eastern Africa.
      The results highlight countries and regions with a high degree of exposure to
      coastal flooding and help identifying regions where policies and adaptive
      planning for building resilient coastal communities are not only desirable but
      essential. Furthermore, we identify needs for further research and scope for
      improvement in this kind of scenario-based exposure analysis. 

PMID- 25760038
TI  - Prediction of chemical respiratory sensitizers using GARD, a novel in vitro assay
      based on a genomic biomarker signature.
AB  - BACKGROUND: Repeated exposure to certain low molecular weight (LMW) chemical
      compounds may result in development of allergic reactions in the skin or in the
      respiratory tract. In most cases, a certain LMW compound selectively sensitize
      the skin, giving rise to allergic contact dermatitis (ACD), or the respiratory
      tract, giving rise to occupational asthma (OA). To limit occurrence of allergic
      diseases, efforts are currently being made to develop predictive assays that
      accurately identify chemicals capable of inducing such reactions. However, while
      a few promising methods for prediction of skin sensitization have been described,
      to date no validated method, in vitro or in vivo, exists that is able to
      accurately classify chemicals as respiratory sensitizers. RESULTS: Recently, we
      presented the in vitro based Genomic Allergen Rapid Detection (GARD) assay as a
      novel testing strategy for classification of skin sensitizing chemicals based on
      measurement of a genomic biomarker signature. We have expanded the applicability
      domain of the GARD assay to classify also respiratory sensitizers by identifying
      a separate biomarker signature containing 389 differentially regulated genes for
      respiratory sensitizers in comparison to non-respiratory sensitizers. By using an
      independent data set in combination with supervised machine learning, we
      validated the assay, showing that the identified genomic biomarker is able to
      accurately classify respiratory sensitizers. CONCLUSIONS: We have identified a
      genomic biomarker signature for classification of respiratory sensitizers.
      Combining this newly identified biomarker signature with our previously
      identified biomarker signature for classification of skin sensitizers, we have
      developed a novel in vitro testing strategy with a potent ability to predict both
      skin and respiratory sensitization in the same sample.

PMID- 25760039
TI  - Characterization of course and terrain and their effect on skier speed in World
      Cup alpine ski racing.
AB  - World Cup (WC) alpine ski racing consists of four main competition disciplines
      (slalom, giant slalom, super-G and downhill), each with specific course and
      terrain characteristics. The International Ski Federation (FIS) has regulated
      course length, altitude drop from start to finish and course setting in order to
      specify the characteristics of the respective competition disciplines and to
      control performance and injury-related aspects. However to date, no detailed data
      on course setting and its adaptation to terrain is available. It is also unknown
      how course and terrain characteristics influence skier speed. Therefore, the aim
      of the study was to characterize course setting, terrain geomorphology and their
      relationship to speed in male WC giant slalom, super-G and downhill. The study
      revealed that terrain was flatter in downhill compared to the other disciplines.
      In all disciplines, variability in horizontal gate distance (gate offset) was
      larger than in gate distance (linear distance from gate to gate). In giant slalom
      the horizontal gate distance increased with terrain inclination, while super-G
      and downhill did not show such a connection. In giant slalom and super-G, there
      was a slight trend towards shorter gate distances as the steepness of the terrain
      increased. Gates were usually set close to terrain transitions in all three
      disciplines. Downhill had a larger proportion of extreme terrain inclination
      changes along the skier trajectory per unit time skiing than the other
      disciplines. Skier speed decreased with increasing steepness of terrain in all
      disciplines except for downhill. In steep terrain, speed was found to be
      controllable by increased horizontal gate distances in giant slalom and by
      shorter gate distances in giant slalom and super-G. Across the disciplines skier
      speed was largely explained by course setting and terrain inclination in a
      multiple linear model. 

PMID- 25760042
TI  - Acute effects of brisk walking on sugary snack cravings in overweight people,
      affect and responses to a manipulated stress situation and to a sugary snack cue:
      a crossover study.
AB  - Research has shown that acute exercise reduces urges for chocolate in normal
      weight people. This study aimed to examine the effects of an acute exercise bout
      on urges to consume sugary snacks, affect as well as 'psychological and
      physiological responses' to stress and a 'sugary snack cue', in overweight
      individuals. Following 3 days of chocolate-abstinence, 47 overweight, sugary
      snack consumers were assessed, in 2 randomly ordered conditions, in a within
      subject design: 15-min brisk walk or passive control. Following each,
      participants completed 2 tasks: Stroop color-word interference task, and handling
      sugary snacks. Urges for sugary snacks, affective activation and valence were
      assessed. ANOVAs revealed significant condition x time interaction effects for:
      urges to consume sugary snacks, affective valence and activation. Obtained data
      show that exercise reduces urges for sugary snacks and attenuates urges in
      response to the stress situation and the cue in overweight people. 

PMID- 25760041
TI  - Effects on murine behavior and lifespan of selectively decreasing expression of
      mutant huntingtin allele by supt4h knockdown.
AB  - Production of protein containing lengthy stretches of polyglutamine encoded by
      multiple repeats of the trinucleotide CAG is a hallmark of Huntington's disease
      (HD) and of a variety of other inherited degenerative neurological and
      neuromuscular disorders. Earlier work has shown that interference with production
      of the transcription elongation protein SUPT4H results in decreased cellular
      capacity to transcribe mutant huntingtin gene (Htt) alleles containing long CAG
      expansions, but has little effect on expression of genes containing short CAG
      stretches. zQ175 and R6/2 are genetically engineered mouse strains whose genomes
      contain human HTT alleles that include greatly expanded CAG repeats and which are
      used as animal models for HD. Here we show that reduction of SUPT4H expression in
      brains of zQ175 mice by intracerebroventricular bolus injection of antisense 2'-O
      methoxyethyl oligonucleotides (ASOs) directed against Supt4h, or in R6/2 mice by
      deletion of one copy of the Supt4h gene, results in a decrease in mRNA and
      protein encoded specifically by mutant Htt alleles. We further show that
      reduction of SUPT4H in mouse brains is associated with decreased HTT protein
      aggregation, and in R6/2 mice, also with prolonged lifespan and delay of the
      motor impairment that normally develops in these animals. Our findings support
      the view that targeting of SUPT4H function may be useful as a therapeutic
      countermeasure against HD. 

PMID- 25760040
TI  - Vitamin B6 in plasma and cerebrospinal fluid of children.
AB  - BACKGROUND: Over the past years, the essential role of vitamin B6 in brain
      development and functioning has been recognized and genetic metabolic disorders
      resulting in functional vitamin B6 deficiency have been identified. However, data
      on B6 vitamers in children are scarce. MATERIALS AND METHODS: B6 vitamer
      concentrations in simultaneously sampled plasma and cerebrospinal fluid (CSF) of
      70 children with intellectual disability were determined by ultra performance
      liquid chromatography-tandem mass spectrometry. For ethical reasons, CSF samples
      could not be obtained from healthy children. The influence of sex, age, epilepsy
      and treatment with anti-epileptic drugs, were investigated. RESULTS: The B6
      vitamer composition of plasma (pyridoxal phosphate (PLP) > pyridoxic acid >
      pyridoxal (PL)) differed from that of CSF (PL > PLP > pyridoxic acid >
      pyridoxamine). Strong correlations were found for B6 vitamers in and between
      plasma and CSF. Treatment with anti-epileptic drugs resulted in decreased
      concentrations of PL and PLP in CSF. CONCLUSION: We provide concentrations of all
      B6 vitamers in plasma and CSF of children with intellectual disability (+/
      epilepsy), which can be used in the investigation of known and novel disorders
      associated with vitamin B6 metabolism as well as in monitoring of the biochemical
      effects of treatment with vitamin B6.

PMID- 25760043
TI  - Cortical consequences of HIV-1 Tat exposure in rats are enhanced by chronic
      cocaine.
AB  - The life span of individuals that are sero-positive for human immunodeficiency
      virus (HIV) has greatly improved; however, complications involving the central
      nervous system (CNS) remain a concern. While HIV does not directly infect
      neurons, the proteins produced by the virus, including HIV transactivator of
      transcription (Tat), are released from infected glia; these proteins can be
      neurotoxic. This neurotoxicity is thought to mediate the pathology underlying
      HIVassociated neurological impairments. Cocaine abuse is common among HIV
      infected individuals, and this abuse augments HIV-associated neurological
      deficits. The brain regions and pathophysiological mechanisms that are
      dysregulated by both chronic cocaine and Tat are the focus of the current review.

PMID- 25760045
TI  - Chronic HIV-1 Tat and HIV reduce Rbfox3/NeuN: evidence for sex-related effects.
AB  - The NeuN antibody has been widely used to identify and quantify neurons in normal
      and disease situations based on binding to a nuclear epitope in most types of
      neurons. This epitope was recently identified as the RNA-binding, feminizing
      locus on X-3 (Rbfox3), a member of the larger, mammalian Fox1 family of RNA
      binding proteins. Fox1 proteins recognize a unique UGCAUG mRNA motif and regulate
      alternative splicing of precursor mRNA to control post-transcriptional events
      important in neuronal differentiation and central nervous system development.
      Recent clinical findings show that Rbfox3/NeuN gene dosage is altered in certain
      human neurodevelopmental disorders, and redistribution has been noted in HIV(+)
      tissue. We hypothesized that HIV-1 Tat might affect Rbfox3/NeuN expression, and
      examined this question in vivo using inducible transgenic mice, and in vitro
      using human mesencephalic-derived neurons. Rbfox3/NeuN expression and
      localization in HIV+ basal ganglia and hippocampus was also examined. Chronic Tat
      exposure reduced Rbfox3/NeuN protein levels and increased cytoplasmic
      localization, similar to the effect of HIV exposure. Cytoplasmic Rbfox3/NeuN
      signal has occasionally been reported, although the meaning or function of
      cytoplasmic versus nuclear localization remains speculative. Importantly,
      Rbfox3/NeuN reductions were more significant in male mice. Although Rbfox3/NeuN
      expressing cells were significantly decreased by Tat exposure, stereology showed
      that Nissl(+) neuron numbers remained normal. Thus, loss of Rbfox3/NeuN may
      relate more to functional change than to neuron loss. The effects of Tat by
      itself are highly relevant to HIV(+) individuals maintained on antiretroviral
      therapy, since Tat is released from infected cells even when viral replication is
      inhibited. 

PMID- 25760047
TI  - HIV-1 Tat protein exposure potentiates ethanol reward and reinstates extinguished
      ethanol-conditioned place preference.
AB  - Exposure to HIV-1 trans-activator of transcription (Tat) protein potentiates the
      psychostimulant effects of cocaine, but the functional consequences of the
      interaction between HIV-1 Tat and other abused drugs is poorly understood. We
      hypothesized that exposure to HIV-1 Tat would potentiate the rewarding effects of
      ethanol. GT-tg transgenic mice, where Tat protein is conditionally expressed in
      brain by a doxycycline-dependent GFAP-linked promoter, were used to test the
      effects of Tat on ethanol-conditioned place preference (CPP). Compared to
      uninduced littermates or doxycycline-treated C57BL/6J mice, Tat-induced GT-tg
      mice demonstrated a 3-fold increase in ethanol-CPP. The potentiation of ethanol
      CPP was dependent on the dose and duration of doxycycline treatment used to
      express Tat protein. Moreover, induction of Tat protein after the extinction of
      CPP produced reinstatement without additional exposure to ethanol. Together,
      these data suggest that CNS exposure to HIV-1 Tat protein potentiates the
      rewarding effects of ethanol in mice. 

PMID- 25760044
TI  - Mechanisms of HIV-1 Tat neurotoxicity via CDK5 translocation and hyper
      activation: role in HIV-associated neurocognitive disorders.
AB  - The advent of more effective antiretroviral therapies has reduced the frequency
      of HIV dementia, however the prevalence of milder HIV associated neurocognitive
      disorders [HAND] is actually rising. Neurodegenerative mechanisms in HAND might
      include toxicity by secreted HIV-1 proteins such as Tat, gp120 and Nef that could
      activate neuro-inflammatory pathways, block autophagy, promote excitotoxicity,
      oxidative stress, mitochondrial dysfunction and dysregulation of signaling
      pathways. Recent studies have shown that Tat could interfere with several signal
      transduction mechanisms involved in cytoskeletal regulation, cell survival and
      cell cycle re-entry. Among them, Tat has been shown to hyper-activate cyclin
      dependent kinase [CDK] 5, a member of the Ser/Thr CDKs involved in cell
      migration, angiogenesis, neurogenesis and synaptic plasticity. CDK5 is activated
      by binding to its regulatory subunit, p35 or p39. For this manuscript we review
      evidence showing that Tat, via calcium dysregulation, promotes calpain-1 cleavage
      of p35 to p25, which in turn hyper-activates CDK5 resulting in abnormal
      phosphorylation of downstream targets such as Tau, collapsin response mediator
      protein-2 [CRMP2], doublecortin [DCX] and MEF2. We also present new data showing
      that Tat interferes with the trafficking of CDK5 between the nucleus and
      cytoplasm. This results in prolonged presence of CDK5 in the cytoplasm leading to
      accumulation of aberrantly phosphorylated cytoplasmic targets [e.g.: Tau, CRMP2,
      DCX] that impair neuronal function and eventually lead to cell death. Novel
      therapeutic approaches with compounds that block Tat mediated hyper-activation of
      CDK5 might be of value in the management of HAND. 

PMID- 25760048
TI  - Endothelial Protein C Receptor Gene Variants and Risk of Thrombosis.
AB  - Endothelial protein C receptor (EPCR) is a candidate mediator in the pathogenesis
      of thrombosis, as several data in the literature indicate that polymorphisms such
      as EPCR 4678G/C and 4600A/G are associated with either protective effect or
      increased risk of thrombosis, respectively. We investigated the prevalence of
      these polymorphisms in patients with thrombotic disorders as well as their impact
      on the risk of thrombosis, the age of first thrombotic episode, and recurrence.
      The prevalence of the rare EPCR alleles 4600G and 4678C was comparable in
      patients and controls. However, in a subset analysis, we observed that 4600G
      allele was more prevalent among patients who developed thrombosis at younger age
      (<35 years). Moreover, the prevalence of 4678C allele was significantly lower in
      younger patients compared to older patients. Neither polymorphism seemed to have
      an impact on recurrence regardless of age. Soluble EPCR levels were elevated in
      4600AG patients compared to controls while 4678CC patients presented with lower
      levels of soluble form of EPCR compared to carriers of at least 1 4678G allele.
      Our data suggest that either the lack of the protective EPCR 4678C allele or the
      presence of EPCR 4600G allele may be associated with earlier development of
      thrombosis. 

PMID- 25760049
TI  - Gate-controlled mid-infrared light bending with aperiodic graphene nanoribbons
      array.
AB  - Graphene plasmonic nanostructures enable subwavelength confinement of
      electromagnetic energy from the mid-infrared down to the terahertz frequencies.
      By exploiting the spectrally varying light scattering phase at the vicinity of
      the resonant frequency of the plasmonic nanostructure, it is possible to control
      the angle of reflection of an incoming light beam. We demonstrate, through full
      wave electromagnetic simulations based on Maxwell equations, the electrical
      control of the angle of reflection of a mid-infrared light beam by using an
      aperiodic array of graphene nanoribbons, whose widths are engineered to produce a
      spatially varying reflection phase profile that allows for the construction of a
      far-field collimated beam towards a predefined direction. 

PMID- 25760046
TI  - Opiate addiction therapies and HIV-1 Tat: interactive effects on glial [Ca2+]i,
      oxyradical and neuroinflammatory chemokine production and correlative
      neurotoxicity.
AB  - Few preclinical studies have compared the relative therapeutic efficacy of
      medications used to treat opiate addiction in relation to neuroAIDS. Here we
      compare the ability of methadone and buprenorphine, and the prototypic opiate
      morphine, to potentiate the neurotoxic and proinflammatory ([Ca2+]i, ROS, H2O2,
      chemokines) effects of HIV-1 Tat in neuronal and/or mixed-glial co-cultures.
      Repeated observations of neurons during 48 h exposure to combinations of Tat,
      equimolar concentrations (500 nM) of morphine, methadone, or buprenorphine
      exacerbated neurotoxicity significantly above levels seen with Tat alone.
      Buprenorphine alone displayed marked neurotoxicity at 500 nM, prompting
      additional studies of its neurotoxic effects at 5 nM and 50 nM concentrations +/-
      Tat. In combination with Tat, buprenorphine displayed paradoxical, concentration
      dependent, neurotoxic and neuroprotective actions. Buprenorphine neurotoxicity
      coincided with marked elevations in [Ca2+]i, but not increases in glial ROS or
      chemokine release. Tat by itself elevated the production of CCL5/RANTES, CCL4/MIP
      1beta, and CCL2/MCP-1. Methadone and buprenorphine alone had no effect, but
      methadone interacted with Tat to further increase production of CCL5/RANTES. In
      combination with Tat, all drugs significantly increased glial [Ca2+]i, but ROS
      was only significantly increased by co-exposure with morphine. Taken together,
      the increases in glial [Ca2+]i, ROS, and neuroinflammatory chemokines were not
      especially accurate predictors of neurotoxicity. Despite similarities, opiates
      displayed differences in their neurotoxic and neuroinflammatory interactions with
      Tat. Buprenorphine, in particular, was partially neuroprotective at a low
      concentration, which may result from its unique pharmacological profile at
      multiple opioid receptors. Overall, the results reveal differences among
      addiction medications that may impact neuroAIDS.

PMID- 25760051
TI  - An SVM-based solution for fault detection in wind turbines.
AB  - Research into fault diagnosis in machines with a wide range of variable loads and
      speeds, such as wind turbines, is of great industrial interest. Analysis of the
      power signals emitted by wind turbines for the diagnosis of mechanical faults in
      their mechanical transmission chain is insufficient. A successful diagnosis
      requires the inclusion of accelerometers to evaluate vibrations. This work
      presents a multi-sensory system for fault diagnosis in wind turbines, combined
      with a data-mining solution for the classification of the operational state of
      the turbine. The selected sensors are accelerometers, in which vibration signals
      are processed using angular resampling techniques and electrical, torque and
      speed measurements. Support vector machines (SVMs) are selected for the
      classification task, including two traditional and two promising new kernels.
      This multi-sensory system has been validated on a test-bed that simulates the
      real conditions of wind turbines with two fault typologies: misalignment and
      imbalance. Comparison of SVM performance with the results of artificial neural
      networks (ANNs) shows that linear kernel SVM outperforms other kernels and ANNs
      in terms of accuracy, training and tuning times. The suitability and superior
      performance of linear SVM is also experimentally analyzed, to conclude that this
      data acquisition technique generates linearly separable datasets. 

PMID- 25760052
TI  - An efficient mosaic algorithm considering seasonal variation: application to
      KOMPSAT-2 satellite images.
AB  - As the aerospace industry grows, images obtained from Earth observation
      satellites have been successfully used in various fields. Specifically, the
      demand for a high-resolution (HR) optical images is gradually increasing, and
      hence the generation of a high-quality mosaic image is being magnified as an
      interesting issue. In this paper, we have proposed an efficient mosaic algorithm
      for HR optical images that are significantly different due to seasonal change.
      The algorithm includes main steps such as: (1) seamline extraction from gradient
      magnitude and seam images; (2) histogram matching; and (3) image feathering.
      Eleven Kompsat-2 images characterized by seasonal variations are used for the
      performance validation of the proposed method. The results of the performance
      test show that the proposed method effectively mosaics Kompsat-2 adjacent images
      including severe seasonal changes. Moreover, the results reveal that the proposed
      method is applicable to HR optic images such as GeoEye, IKONOS, QuickBird,
      RapidEye, SPOT, WorldView, etc. 

PMID- 25760053
TI  - A trajectory and orientation reconstruction method for moving objects based on a
      moving monocular camera.
AB  - We propose a monocular trajectory intersection method to solve the problem that a
      monocular moving camera cannot be used for three-dimensional reconstruction of a
      moving object point. The necessary and sufficient condition of when this method
      has the unique solution is provided. An extended application of the method is to
      not only achieve the reconstruction of the 3D trajectory, but also to capture the
      orientation of the moving object, which would not be obtained by PnP problem
      methods due to lack of features. It is a breakthrough improvement that develops
      the intersection measurement from the traditional "point intersection" to
      "trajectory intersection" in videometrics. The trajectory of the object point can
      be obtained by using only linear equations without any initial value or
      iteration; the orientation of the object with poor conditions can also be
      calculated. The required condition for the existence of definite solution of this
      method is derived from equivalence relations of the orders of the moving
      trajectory equations of the object, which specifies the applicable conditions of
      the method. Simulation and experimental results show that it not only applies to
      objects moving along a straight line, or a conic and another simple trajectory,
      but also provides good result for more complicated trajectories, making it widely
      applicable. 

PMID- 25760054
TI  - Magnetization reversal and magnetic anisotropy in ordered CoNiP nanowire arrays:
      effects of wire diameter.
AB  - Ordered CoNiP nanowires with the same length of 4 um and varying diameters (d =
      100 nm-600 nm) were fabricated by electrodeposition of CoNiP onto polycarbonate
      templates. X-ray diffraction, scanning electron microscopy, and high-resolution
      transmission electron microscopy confirmed the quality of the fabricated
      nanowires. Magnetic measurements and theoretical analysis revealed that the
      magnetization reversal and magnetic anisotropy were significantly influenced by
      varying of the diameters of the nanowires. There existed a critical wire diameter
      (dc ~ 276 nm), below which the magnetization reversal occurred via a coherent
      rotation mode, and above which the magnetization reversal occurred via a curling
      rotation mode. The easy axis of the magnetization tended to change in direction
      from parallel to perpendicular with respect to the wire axis as the wire diameter
      exceeded dc ~ 276 nm. With increasing wire diameter, the coercive field (Hc) and
      the remanent to saturation magnetization ratio (Mr/Ms) were also found to rapidly
      decrease in the range d = 100-400 nm and gradually decrease for d > 400 nm. 

PMID- 25760055
TI  - Use of a modified vector model for odor intensity prediction of odorant mixtures.
AB  - Odor intensity (OI) indicates the perceived intensity of an odor by the human
      nose, and it is usually rated by specialized assessors. In order to avoid
      restrictions on assessor participation in OI evaluations, the Vector Model which
      calculates the OI of a mixture as the vector sum of its unmixed components' odor
      intensities was modified. Based on a detected linear relation between the OI and
      the logarithm of odor activity value (OAV-a ratio between chemical concentration
      and odor threshold) of individual odorants, OI of the unmixed component was
      replaced with its corresponding logarithm of OAV. The interaction coefficient
      (cosalpha) which represented the degree of interaction between two constituents
      was also measured in a simplified way. Through a series of odor intensity
      matching tests for binary, ternary and quaternary odor mixtures, the modified
      Vector Model provided an effective way of relating the OI of an odor mixture with
      the lnOAV values of its constituents. Thus, OI of an odor mixture could be
      directly predicted by employing the modified Vector Model after usual
      quantitative analysis. Besides, it was considered that the modified Vector Model
      was applicable for odor mixtures which consisted of odorants with the same
      chemical functional groups and similar molecular structures. 

PMID- 25760056
TI  - Optical sensing of the fatigue damage state of CFRP under realistic aeronautical
      load sequences.
AB  - We present an optical sensing methodology to estimate the fatigue damage state of
      structures made of carbon fiber reinforced polymer (CFRP), by measuring
      variations on the surface roughness. Variable amplitude loads (VAL), which
      represent realistic loads during aeronautical missions of fighter aircraft
      (FALSTAFF) have been applied to coupons until failure. Stiffness degradation and
      surface roughness variations have been measured during the life of the coupons
      obtaining a Pearson correlation of 0.75 between both variables. The data were
      compared with a previous study for Constant Amplitude Load (CAL) obtaining
      similar results. Conclusions suggest that the surface roughness measured in
      strategic zones is a useful technique for structural health monitoring of CFRP
      structures, and that it is independent of the type of load applied. Surface
      roughness can be measured in the field by optical techniques such as speckle,
      confocal perfilometers and interferometry, among others. 

PMID- 25760057
TI  - A performance improvement method for low-cost land vehicle GPS/MEMS-INS attitude
      determination.
AB  - Global positioning system (GPS) technology is well suited for attitude
      determination. However, in land vehicle application, low-cost single frequency
      GPS receivers which have low measurement quality are often used, and external
      factors such as multipath and low satellite visibility in the densely built-up
      urban environment further degrade the quality of the GPS measurements. Due to the
      low-quality receivers used and the challenging urban environment, the success
      rate of the single epoch ambiguity resolution for dynamic attitude determination
      is usually quite low. In this paper, a micro-electro-mechanical system (MEMS)
      inertial navigation system (INS)-aided ambiguity resolution method is proposed to
      improve the GPS attitude determination performance, which is particularly
      suitable for land vehicle attitude determination. First, the INS calculated
      baseline vector is augmented with the GPS carrier phase and code measurements.
      This improves the ambiguity dilution of precision (ADOP), resulting in better
      quality of the unconstrained float solution. Second, the undesirable float
      solutions caused by large measurement errors are further filtered and replaced
      using the INS-aided ambiguity function method (AFM). The fixed solutions are then
      obtained by the constrained least squares ambiguity decorrelation (CLAMBDA)
      algorithm. Finally, the GPS/MEMS-INS integration is realized by the use of a
      Kalman filter. Theoretical analysis of the ADOP is given and experimental results
      demonstrate that our proposed method can significantly improve the quality of the
      float ambiguity solution, leading to high success rate and better accuracy of
      attitude determination. 

PMID- 25760058
TI  - MicroRNA-326 functions as a tumor suppressor in colorectal cancer by targeting
      the nin one binding protein.
AB  - Accumulating evidence has demonstrated that microRNAs (miRNAs) are involved in
      multiple processes in cancer development and progression. miR-326 has been
      identified as a tumor suppressor miRNA in several types of human cancer. However,
      the specific function of miR-326 and its target the nin one binding protein
      (NOB1) in colorectal carcinoma (CRC) remains unclear. In the present study, we
      found that miR-326 inhibited cell proliferation, migration and invasion, and
      induced cell apoptosis and cell cycle arrest of CRC cells by directly targeting
      NOB1. Furthermore, the upregulation of miR-326 in CRC cells was revealed to be
      associated with a feedback loop involving downregulation of the NOB1, which
      mimics the phenotype induced by miR-326. Importantly, we found that the CRC
      patients with high expression of miR-326 or low expression of NOB1 tend to obtain
      a better prognosis. Thus, for the first time, we provide convincing evidence that
      downregulation of miR-326 inhibited tumor proliferation and tumor metastasis by
      directly targeting NOB1 in CRC. NOB1 and miR-326 could be potential therapeutic
      targets for CRC. 

PMID- 25760059
TI  - Overexpression of serine/threonine-protein kinase-1 in pancreatic cancer tissue:
      Serine/threonine-protein kinase-1 knockdown increases the chemosensitivity of
      pancreatic cancer cells.
AB  - Serine/threonine-protein kinase-1 (SMG-1) belongs to the phosphatidylinositol 3
      kinase-related kinase family. Altered expression of SMG-1 contributes to human
      carcinogenesis and cancer progression. The present study detected the expression
      levels of SMG-1 in normal and cancerous pancreatic tissues and then assessed the
      effects of SMG-1-knockdown in pancreatic cancer cell lines in vitro. A pancreatic
      cancer tissue array and pancreatic cancer cell lines were used to detect the
      expression levels of SMG-1 and a lentivirus expressing either SMG-1 or negative
      control short hairpin (sh)RNA were used to knock down the expression of SMG-1 in
      the pancreatic cancer cell lines. Western blot, cell proliferation, Cell Counting
      kit-8, Transwell tumor cell migration and invasion assays, and flow cytometric
      analysis of cell apoptosis with or without gemcitabine or cisplatin treatment
      were performed to assess the tumor cells. The protein expression of SMG-1 was
      higher in the pancreatic cancer tissues and cells compared with the normal
      tissues. sh-SMG-1 lentivirus infection significantly suppressed the expression of
      SMG-1 in the pancreatic cancer cell lines, resulting in the inhibition of tumor
      cell proliferation and increased chemosensitivity to treatment with gemcitabine
      and cisplatin. However, SMG-1 knockdown had no effect on pancreatic cancer cell
      migration or invasion capacities. The protein expression of SMG-1 was increased
      in the pancreatic cancer tissues and was associated with an advanced tumor stage.
      Knock down of the expression of SMG-1 inhibited tumor cell proliferation and
      induced the chemosensitivity of pancreatic cancer cells in vitro.

PMID- 25760060
TI  - iTRAQ-based quantitative proteomic analysis of cerebrospinal fluid reveals NELL2
      as a potential diagnostic biomarker of tuberculous meningitis.
AB  - Tuberculous meningitis (TBM) is a serious complication of tuberculosis that
      affects the central nervous system. As TBM may result in permanent sequelae and
      death, rapid, accurate diagnostic tests using novel biomarkers are required for
      the early diagnosis and treatment of TBM. A quantitative proteomic study was
      therefore performed to identify differential proteins in the cerebrospinal fluid
      (CSF) obtained from TBM patients (n=12) and healthy controls (n=12). CSF samples
      were labelled with iTRAQTM and analyzed by LC-MS/MS. Gene ontology and Pathway
      analysis were conducted using DAVID bioinformatics resources. Neural epidermal
      growth factor-like like 2 (NELL2) with the largest fold-change value was selected
      for validation by western blotting. Proteomic phenotyping revealed over
      representation in two inflammation-associated processes, complement and
      coagulation cascades as well as cell adhesion molecules. Western blotting showed
      a significant decrease in NELL2 levels in TBM subjects compared to healthy
      controls. The AUC analysis revealed NELL2 was able to distinguish TBM subjects
      from healthy controls with 83.3% sensitivity and 75% specificity. In conclusion,
      the results showed that CSF NELL2 is a potential diagnostic biomarker for TBM.
      Further evaluation of these findings in larger studies including anti
      tuberculosis medicated and unmedicated patient cohorts with other intracranial
      infectious diseases is required for clinical translation.

PMID- 25760061
TI  - [Gender-specific differences relating to depressiveness in 1st and 2nd generation
      migrants: results of a cross-sectional study amongst employees of a university
      hospital].

PMID- 25760062
TI  - alphaB-crystallin reduces ristocetin-induced soluble CD40 ligand release in human
      platelets: suppression of thromboxane A2 generation.
AB  - Our group has previously shown that alphaB-crystallin (HSPB5), a small heat shock
      protein, inhibits human platelet aggregation by ristocetin, an activator of
      glycoprotein Ib/IX/V. In addition, it was demonstrated that glycoprotein Ib/IX/V
      activation induces soluble CD40 (sCD40) ligand release via thromboxane (TX) A2.
      In the present study, the effect of alphaB-crystallin on the ristocetin-induced
      sCD40 ligand release in human platelets was investigated. The ristocetin-induced
      release of sCD40 ligand was suppressed by alphaB-crystallin. In addition, alphaB
      crystallin reduced the ristocetin-stimulated production of 11-dehydro-TX B2, a
      stable metabolite of TXA2. alphaB-crystallin did not suppress the platelet
      aggregation induced by U46619, a TXA2 receptor agonist. alphaB-crystallin had
      little effect on the U46619-induced phosphorylation of p38 mitogen-activated
      protein kinase or sCD40 ligand release. In addition, alphaB-crystallin failed to
      reduce the binding of SZ2, a monoclonal antibody against the sulfated sequence in
      the alpha-chain of glycoprotein Ib, to the ristocetin-stimulated platelets. These
      results strongly suggest that alphaB-crystallin extracellularly suppresses
      ristocetin-stimulated release of sCD40 ligand by inhibiting the TXA2 production
      in human platelets.

PMID- 25760063
TI  - Integrated microRNA-mRNA analysis revealing the potential roles of microRNAs in
      tongue squamous cell cancer.
AB  - Tongue squamous cell carcinoma (TSCC) is a rare and aggressive type of cancer,
      which is associated with a poor prognosis. Identification of patients at high
      risk of TSCC tumorigenesis may provide information for the early detection of
      metastases, and for potential treatment strategies. MicroRNA (miRNA; miR) and
      mRNA expression profiling of TSCC tissue samples and normal control tissue
      samples were obtained from three Gene Expression Omnibus (GEO) data series.
      Bioinformatics analyses, including the Gene Ontology (GO) and Kyoto Encyclopedia
      of Genes and Genomes were used to identify genes and pathways specifically
      associated with miRNA-associated TSCC oncology. A total of 25 miRNAs and 769
      mRNAs were differentially expressed in the two groups assessed, and all the
      differentially expressed miRNA and mRNA target interactions were analyzed. The
      miRNA target genes were predominantly associated with 38 GO terms and 13
      pathways. Of the genes differentially expressed between the two groups, and
      confirmed in another GEO series, miRNA-494, miRNA-96, miRNA-183, runt-related
      transcription factor 1, programmed cell death protein 4 and membrane-associated
      guanylate kinase were the most significantly altered, and may be central in the
      regulation of TSCC. Bioinformatics may be used to analyze large quantities of
      data in microarrays through rigorous experimental planning, statistical analysis
      and the collection of complete data on TSCC. In the present study, a novel
      differential miRNA-mRNA expression network was constructed, and further
      investigation may provide novel targets for the diagnosis of TSCC.

PMID- 25760064
TI  - Down syndrome: a risk factor for malocclusion severity?
AB  - The aims of the present study were to compare aspects related to malocclusion
      between individuals with Down syndrome (DS) and a control group, establish
      malocclusion severity, and identify determinant factors. A total of 120
      individuals (60 with DS and 60 with no physical or mental impairment), were
      included in the study. Data were collected through interviews, analyses of the
      medical charts, and oral examinations. The criteria of the Dental Aesthetic Index
      were used for the diagnosis of malocclusion. Chi-square test (p <= 0.05) and
      multivariate logistic regression were used for comparisons between the two groups
      and to determine the association between the dependent (malocclusion severity)
      and independent variables. Statistically significant differences were found
      between the two groups for the following variables: missing teeth, diastema,
      overjet, mandibular protrusion, anterior open bite, posterior crossbite, facial
      type, lip incompetence, and Angle classification. DS, a history of premature
      birth, and long face pattern were found to be associated with malocclusion
      severity. Individuals with DS exhibited more occlusal problems than those in the
      control group. 

PMID- 25760065
TI  - Dentin hypersensitivity treatment of non-carious cervical lesions - a single
      blind, split-mouth study.
AB  - This study aims to compare the in vivo effect of a desensitizing therapy
      associated with a restorative technique for the treatment of cervical dentin
      hypersensitivity (CDH) in non-carious lesions. The sample consisted of 68 teeth
      with moderate or severe dentin hypersensitivity in 17 individuals (one tooth per
      quadrant). The sensitivity levels of the teeth were scored, and the teeth were
      randomly distributed into four groups: T1 - desensitizing gel applied once per
      week until remission of pain; T2 - desensitizing gel applied once per week
      followed immediately by restoration with resin composite (Filtek Z250, 3M Espe);
      T3 - desensitizing gel once per week until remission of pain and then restoration
      with resin composite; and T4 - restoration with resin composite. Dentin
      hypersensitivity was assessed at 0, 7, 30, 90 and 180 days. The Kruskal-Wallis,
      Wilcoxon and Mann-Whitney (p < 0.05) tests were used to compare the treatments.
      The mean baseline CDH scores were T1 - 2.41, T2 - 2.41, T3 - 2.47, and T4 - 2.70
      (p > 0.05). At seven and 180 days, the mean CDH scores were as follows: T1 -
      1.47/0.65, T2 - 1.35/0.71, T3 - 0.71/0.53, and T4 - 1.12/0.59, all of which were
      significantly lower (p < 0.001) than the baseline scores. The scores at 30, 90
      and 180 days were not significantly different when compared to the score of the
      previous period. At 180 days, CDH scores were similar among groups (p > 0.05).
      Teeth with moderate or severe hypersensitivity that required a filling responded
      similarly regardless of whether the desensitizing procedure was carried out prior
      to the filling. 

PMID- 25760066
TI  - Fluoride concentrations in the water of Maringa, Brazil, considering the
      benefit/risk balance of caries and fluorosis.
AB  - Current Brazilian law regarding water fluoridation classification is dichotomous
      with respect to the risks of and benefits for oral diseases, and fluoride (F)
      concentrations less than 0.6 or above 0.8 mg F/L are considered outside the
      normal limits. Thus, the law does not consider that both caries and fluorosis are
      dependent on the dosage and duration of fluoride exposure because they are both
      chronic diseases. Therefore, this study evaluated the quality of water
      fluoridation in Maringa, PR, Brazil, considering a new classification for the
      concentration of F in water the supply, based on the anticaries benefit and risk
      of fluorosis (CECOL/USP, 2011). Water samples (n = 325) were collected monthly
      over one year from 28 distribution water networks: 20 from treatment plants and 8
      from artesian wells. F concentrations were determined using a specific ion
      electrode. The average F concentration was 0.77 mg F/L (ppm F), ranging from 0.44
      to 1.22 mg F/L. Considering all of the water samples analyzed, 83.7% of them
      presented from 0.55 to 0.84 mg F/L, and according to the new classification used,
      they would provide maximum anticaries benefit with a low risk of fluorosis. This
      percentage was lower (75.4%) in the water samples supplied from artesian wells
      than from those distributed by the treatment plant (86%). In conclusion, based on
      the new classification of water F concentrations, the quality of water
      fluoridation in Maringa is adequate and is within the range of the best balance
      between risk and benefit. 

PMID- 25760067
TI  - Evaluation of mandibular condyles in children with unilateral posterior
      crossbite.
AB  - The relationship of mandibular condyle dimensions and its association with
      unilateral posterior crossbite (UPXB) has been suggested in the literature. The
      purpose of this prospective study was to evaluate mandibular condyles on the left
      and right sides and between crossed and non-crossed sides in the sagittal and
      coronal planes, using cone-beam computed tomography (CBCT). Twenty CBCT images of
      40 temporo mandibular joints (TMJs) in individuals in mixed dentition phase,
      which included 9 males (mean 7.9 years) and 11 females (mean 8.2 years), with
      unilateral posterior crossbite without premature contacts and functional
      mandibular shifts and with transverse maxillary deficiency. The criteria for
      sample exclusion included the presence of painful symptoms, facial trauma
      history, systemic diseases such as juvenile rheumatoid arthritis, mouth opening
      limitation (< 40 mm), congenital or genetic anomalies, and skeletal asymmetries
      that may result in TMJ disorders. Dimensional measurements of the condyles
      between the right and left sides and crossed and non-crossed sides in sagittal
      and coronal view were made. There was no significant difference between the
      measurements of the crossed and non-crossed sides in both sagittal and coronal
      view. These findings suggest that the presence of unilateral posterior crossbite
      in children with UPXB did not result in changes between the mandibular condyles
      in the right and left sides or between the crossed and non-crossed sides in the
      coronal or sagittal plane. 

PMID- 25760068
TI  - Epidemiological evaluation of apical periodontitis prevalence in an urban
      Brazilian population.
AB  - The present study aimed to assess the prevalence of apical periodontitis (AP) in
      an urban Brazilian population according to gender, age group and tooth type. Data
      were collected from clinical files containing the medical and dental histories
      and periapical radiographs of 1,126 patients treated at the School of Dentistry
      at Universidade do Estado do Rio de Janeiro between March 2000 and December 2010.
      A total of 15,724 periapical radiographs were evaluated. All the radiographs were
      evaluated by two independent, previously calibrated endodontists (kappa = 0.88).
      Periapical areas on the radiographs were classified as N (normal) or AR (apical
      radiolucency). The frequency of AP and the 95% Confidence Interval (95%CI) were
      calculated according to gender, age group and tooth type. Differences between
      groups were calculated using the Z-test at a significance level of 5% (p < 0.05).
      AP was present in 7.87% of the samples, with 16.70% occurring on previously
      endodontically treated teeth and 44.65% occurring on teeth referred for
      endodontic treatment (TR-RCT). The frequency of AP was higher among females (64%)
      than among males (35%). The central and lateral maxillary incisors were the most
      frequently affected teeth. The frequency of AP was higher among individuals
      between 30 and 49 years of age. In this population, AP was more prevalent among
      females and among individuals between 30 and 49 years of age, and the central and
      lateral maxillary incisors were the most frequently affected teeth. 

PMID- 25760069
TI  - Evaluation of the effects of Angelicae dahuricae radix on the morphology and
      viability of mesenchymal stem cells.
AB  - Angelicae dahuricae radix is a traditional herbal medicine used to treat various
      diseases in China and Korea, such as colds, headaches, rhinitis and psoriasis.
      Angelicae dahuricae radix has been used as an anti-inflammatory, analgesic,
      antipyretic and antioxidant remedy. This study was performed in order to evaluate
      the effects of the extracts of Angelicae dahuricae radix on the morphology and
      viability of mesenchymal stem cells derived from the gingiva. Mesenchymal stem
      cells derived from the gingiva were grown in the presence of Angelicae dahuricae
      radix at final concentrations that ranged from 0.001 to 100 ug/ml. The morphology
      of the cells was viewed under an inverted microscope, and the analysis of cell
      proliferation was performed with cell counting kit-8 (CCK-8) on days 1, 3 and 7.
      The cells in the control group had spindle-shaped, fibroblast-like morphology at
      days 1, 3 and 7 under optical microscopy. The shapes of the cells in 0.001, 0.01,
      0.1, 1, 10 and 100 ug/ml Angelicae dahuricae radix were similar to the shapes of
      the cells in the control group. The relative values of the CCK-8 assays of 0.001,
      0.01, 0.1, 1, 10, and 100 ug/ml Angelicae dahuricae radix were 102.5 +/- 0.6,
      133.3 +/- 9.6, 148.4 +/- 20.5, 147.7 +/- 12.6, 132.3 +/- 27.7 and 101.1 +/- 4.6%,
      respectively, when the CCK-8 result of the control group on day 1 was considered
      to be 100%. There was a marginal increase in cell proliferation at 0.1 and 1
      ug/ml groups at day 1; however, this did not achieve statistical significance
      (P=0.052). The relative values of the CCK-8 assays of 0.001, 0.01, 0.1, 1, 10 and
      100 ug/ml Angelicae dahuricae radix were 96.5 +/- 1.3, 89.3 +/- 0.9, 90.3 +/-
      3.0, 84.8 +/- 12.2, 92.3 +/- 4.5 and 86.8 +/- 11.7%, respectively, when the CCK-8
      result of the control group on day 3 was considered to be 100% (P>0.05). The
      relative values of the CCK-8 assays of 0.001, 0.01, 0.1, 1, 10 and 100 ug/ml
      Angelicae dahuricae radix day 7 were 94.9 +/- 22.3, 102.8 +/- 22.1, 127.4 +/-
      7.4, 130.4 +/- 1.3, 129.2 +/- 10.8 and 124.8 +/- 9.1%, respectively, when the CCK
      8 result of the control group on day 7 was considered to be 100%, but there were
      no statistically significant differences among the groups (P>0.05). Within the
      limits of this study, Angelicae dahuricae radix at the tested concentrations did
      not produce statistically significant differences in the viability of stem cells
      derived from the gingiva.

PMID- 25760070
TI  - Osmylated DNA, a novel concept for sequencing DNA using nanopores.
AB  - Saenger sequencing has led the advances in molecular biology, while faster and
      cheaper next generation technologies are urgently needed. A newer approach
      exploits nanopores, natural or solid-state, set in an electrical field, and
      obtains base sequence information from current variations due to the passage of a
      ssDNA molecule through the pore. A hurdle in this approach is the fact that the
      four bases are chemically comparable to each other which leads to small
      differences in current obstruction. 'Base calling' becomes even more challenging
      because most nanopores sense a short sequence and not individual bases. Perhaps
      sequencing DNA via nanopores would be more manageable, if only the bases were
      two, and chemically very different from each other; a sequence of 1s and 0s comes
      to mind. Osmylated DNA comes close to such a sequence of 1s and 0s. Osmylation is
      the addition of osmium tetroxide bipyridine across the C5-C6 double bond of the
      pyrimidines. Osmylation adds almost 400% mass to the reactive base, creates a
      sterically and electronically notably different molecule, labeled 1, compared to
      the unreactive purines, labeled 0. If osmylated DNA were successfully sequenced,
      the result would be a sequence of osmylated pyrimidines (1), and purines (0), and
      not of the actual nucleobases. To solve this problem we studied the osmylation
      reaction with short oligos and with M13mp18, a long ssDNA, developed a UV-vis
      assay to measure extent of osmylation, and designed two protocols. Protocol A
      uses mild conditions and yields osmylated thymidines (1), while leaving the other
      three bases (0) practically intact. Protocol B uses harsher conditions and
      effectively osmylates both pyrimidines, but not the purines. Applying these two
      protocols also to the complementary of the target polynucleotide yields a total
      of four osmylated strands that collectively could define the actual base sequence
      of the target DNA. 

PMID- 25760071
TI  - A novel cancer immunotherapy based on the combination of a synthetic carbohydrate
      pulsed dendritic cell vaccine and glycoengineered cancer cells.
AB  - Immune tolerance to tumor-associated carbohydrate antigens (TACAs) has severely
      restricted the usefulness of most TACAs. To overcome this problem, we selected a
      sialylated trisaccharide TACA, GM3, as a target antigen, and tested a new
      immunotherapeutic strategy by combining metabolic bioengineering with dendritic
      cell (DC) vaccination. We engineered cancer cells to express an artificial
      structure, N-phenylacetyl-D-neuraminic acid, in place of the natural N-acetyl-D
      neuraminic acid of GM3 by using N-phenylacetyl-D-mannosamine (ManNPhAc) as a
      biosynthetic precursor. Next, we selectively targeted the bioengineered cancer
      cells by vaccination with DCs pulsed with the GM3 N-phenylacetyl derivative.
      Vaccination with GM3NPhAc-KLH-loaded DCs elicited robust GM3NPhAc-specific T cell
      dependent immunity. The results showed that this strategy could significantly
      inhibit FBL3 tumor growth and prolong the survival of tumor-bearing mice; B16F10
      lung metastases could also be reduced. These findings lay out a new strategy for
      overcoming immune tolerance to TACAs, such as GM3, for the development of
      effective tumor immunotherapies. 

PMID- 25760072
TI  - Lung cancer in never-smoker Asian females is driven by oncogenic mutations, most
      often involving EGFR.
AB  - The aim of this study was to determine the distribution of known oncogenic driver
      mutations in female never-smoker Asian patients with lung adenocarcinoma. We
      analyzed 214 mutations across 26 lung cancer-associated genes and three fusion
      genes using the MassARRAY LungCarta Panel and the ALK, ROS1, and RET fusion
      assays in 198 consecutively resected lung adenocarcinomas from never-smoker
      females at a single institution. EGFR mutation, which was the most frequent
      driver gene mutation, was detected in 124 (63%) cases. Mutation of ALK, KRAS,
      PIK3CA, ERBB2, BRAF, ROS1, and RET genesoccurred in 7%, 4%, 2.5%, 1.5%, 1%, 1%,
      and 1% of cases, respectively. Thus, 79% of lung adenocarcinomas from never
      smoker females harbored well-known oncogenic mutations. Mucinous adenocarcinomas
      tended to have a lower frequency of known driver gene mutations than other
      histologic subtypes. EGFR mutation was associated with older age and a
      predominantly acinar pattern, while ALK rearrangement was associated with younger
      age and a predominantly solid pattern. Lung cancer in never-smoker Asian females
      is a distinct entity, with the majority of these cancers developing from
      oncogenic mutations.

PMID- 25760073
TI  - Elevated S100A6 (Calcyclin) enhances tumorigenesis and suppresses CXCL14-induced
      apoptosis in clear cell renal cell carcinoma.
AB  - Clear cell renal cell carcinoma (ccRCC) is often resistant to existing therapy.
      We found elevated S100A6 levels in ccRCC tissues, associated with higher grade
      pathological features and clinical stages in ccRCC patients. Knockdown of S100A6
      inhibited cell proliferation in vitro and tumor growth in vivo. Gene expression
      profiling suggests a novel function of S100A6 in suppressing apoptosis, as well
      as a relationship between S100A6 and CXCL14, a pro-inflammatory chemokine. We
      suggest that the S100A6/CXCL14 signaling pathway is a potential therapeutic
      target in ccRCC. 

PMID- 25760074
TI  - Circadian genes Per1 and Per2 increase radiosensitivity of glioma in vivo.
AB  - Per1 and Per2 play a key role in regulating the circadian rhythm in mammals. We
      report here that although both genes were expressed with a circadian rhythm in
      glioma and normal brain tissue in rats, their expression profiles differed in the
      two types of tissue. In addition, high expression of Per1 and Per2 in glioma
      tissue was associated with increased sensitivity to x-irradiation. No such
      sensitizing effect was observed in normal tissue. Our results suggest that Per1
      and Per2 expression may increase the efficacy of radiotherapy against glioma by
      promoting apoptosis. 

PMID- 25760075
TI  - High expression of TACC3 in esophageal squamous cell carcinoma correlates with
      poor prognosis.
AB  - To analyze the expression of the transforming acidic coiled-coil protein 3
      (TACC3) in esophageal squamous cell carcinoma (ESCC) samples, and to identify
      whether TACC3 can serve as a biomarker for the diagnosis and prognosis of ESCC,
      qPCR, western blotting and immunohistochemistry staining (IHC) were utilized to
      detect the expression of TACC3. Furthermore, cell growth, colony formation,
      migration ability and the epithelial-mesenchymal transition markers of ESCC cells
      in which TACC3 were knocked-down were measured. The mRNA and protein levels of
      TACC3 were higher in ESCC specimens compared to non-tumorous esophageal
      epithelial tissues. IHC results revealed TACC3 expression was significantly
      correlated to differentiation (p = 0.017) and lymphoid nodal status (p = 0.028).
      The patients with high-expression of TACC3 had a significantly poor prognosis
      compared to those of low-expression (p = 0.017), especially in the patients at
      stages I-II (p = 0.028). Multivariate analysis indicated that TACC3 expression
      was an independent prognostic factor for ESCC patients (p = 0.025). Knockdown of
      TACC3 inhibited the ability of cell proliferation, colony formation and
      migration. This study first identifies TACC3 not only as a useful biomarker for
      diagnose and prognosis of ESCC, but also as a potential therapeutic target for
      patients with ESCC. 

PMID- 25760076
TI  - The PDGF-D/miR-106a/Twist1 pathway orchestrates epithelial-mesenchymal transition
      in gemcitabine resistance hepatoma cells.
AB  - Emerging evidence demonstrates that platelet-derived growth factor-D (PDGF-D)
      plays a critical role in epithelial-mesenchymal transition (EMT) and drug
      resistance in hepatocellular carcinoma (HCC) cells. However, the underlying
      mechanism has not been fully elucidated. The objective is to explore the
      molecular mechanism of PDGF-D-mediated EMT in drug resistance HCC cells. To
      achieve our goal, we used multiple approaches including Western blotting, real
      time RT-PCR, wound healing assay, invasion assay, luciferase activity assay,
      transfection, and immunohistochemistry. We found that PDGF-D is highly expressed
      in gemcitabine-resistant (GR) HCC cells. Moreover, PDGF-D markedly inhibited miR
      106a expression and subsequently upregulated Twist1 expression. Notably, PDGF-D
      expression was associated with miR-106a and Twist1 in HCC patients. Our findings
      provide a possible molecular mechanism for understanding GR chemoresistance in
      HCC cells. Therefore, inactivation of PDGF-D/Twist or activation of miR-106a
      could be a novel strategy for the treatment of HCC. 

PMID- 25760077
TI  - Upregulated lncRNA-UCA1 contributes to progression of hepatocellular carcinoma
      through inhibition of miR-216b and activation of FGFR1/ERK signaling pathway.
AB  - The long non-coding RNA (lncRNA) urothelial carcinoma-associated 1 (UCA1) has
      been recently shown to be dysregulated, which plays an important role in the
      progression of several cancers. However, the biological role and clinical
      significance of UCA1 in the carcinogenesis of hepatocellular carcinoma (HCC)
      remain unclear. Herein, we found that UCA1 was aberrantly upregulated in HCC
      tissues and associated with TNM stage, metastasis and postoperative survival.
      UCA1 depletion inhibited the growth and metastasis of HCC cell lines in vitro and
      in vivo. Furthermore, UCA1 could act as an endogenous sponge by directly binding
      to miR-216b and downregulation miR-216b expression. In addition, UCA1 could
      reverse the inhibitory effect of miR-216b on the growth and metastasis of HCC
      cells, which might be involved in the derepression of fibroblast growth factor
      receptor 1 (FGFR1) expression, a target gene of miR-216b, and the activation of
      ERK signaling pathway. Taken together, our data highlights the pivotal role of
      UCA1 in the tumorigenesis of HCC. Moreover, the present study elucidates a novel
      lncRNA-miRNA-mRNA regulatory network that is UCA1-miR-216b-FGFR1-ERK signaling
      pathway in HCC, which may help to lead a better understanding the pathogenesis of
      HCC and probe the feasibility of lncRNA-directed diagnosis and therapy for this
      deadly disease.

PMID- 25760078
TI  - HDAC9 promotes glioblastoma growth via TAZ-mediated EGFR pathway activation.
AB  - Histone deacetylase 9 (HDAC9), a member of class II HDACs, regulates a wide
      variety of normal and abnormal physiological functions. We found that HDAC9 is
      over-expressed in prognostically poor glioblastoma patients. Knockdown HDAC9
      decreased proliferation in vitro and tumor formation in vivo. HDAC9 accelerated
      cell cycle in part by potentiating the EGFR signaling pathway. Also, HDAC9
      interacted with TAZ, a key downstream effector of Hippo pathway. Knockdown of
      HDAC9 decreased the expression of TAZ. We found that overexpressed TAZ in HDAC9
      knockdown cells abrogated the effects induced by HDAC9 silencing both in vitro
      and in vivo. We demonstrated that HDAC9 promotes tumor formation of glioblastoma
      via TAZ-mediated EGFR pathway activation, and provide the evidence for promising
      target for the treatment of glioblastoma.

PMID- 25760079
TI  - Effects of increasing concentrations of sodium sulfite on deoxynivalenol and
      deoxynivalenol sulfonate concentrations of maize kernels and maize meal preserved
      at various moisture content.
AB  - Under moderate climatic conditions, deoxynivalenol (DON) contamination occurs
      frequently on cereals. Detoxification measures are required to avoid adverse
      effects on farm animals. In the present study, a wet preservation method with
      sodium sulfite (Na2SO3) and propionic acid was tested to titrate the optimum
      Na2SO3-dose for maximum DON reduction of contaminated maize kernels and meal and
      to examine the interaction between dose and moisture content in dependence on the
      preservation duration. The DON concentration decreased with increasing amounts of
      supplemented Na2SO3 and with increasing duration of the preservation period in a
      bi-exponential fashion. Additionally, the feed structure and moisture content had
      a significant influence on the decontaminating effect. Variants with 30% moisture
      content favored higher DON reduction rates compared to 14% moisture, but
      especially at low moisture contents, DON reduction was more pronounced in maize
      kernels than in maize meal. In addition to the decrease of DON, a concomitant
      formation of three different DON sulfonates was observed which differed in their
      formation pattern over the time course of preservation. The overall results and
      statistical analysis clarified that Na2SO3 addition of 10 g/kg maize at 30%
      moisture for eight days was necessary to obtain a complete DON reduction. 

PMID- 25760080
TI  - Detection of ochratoxin A using molecular beacons and real-time PCR thermal
      cycler.
AB  - We developed a simple and cheap assay for quantitatively detecting ochratoxin A
      (OTA) in wine. A DNA aptamer available in literature was used as recognition
      probe in its molecular beacon form, i.e., with a fluorescence-quenching pair at
      the stem ends. Our aptabeacon could adopt a conformation allowing OTA binding,
      causing a fluorescence rise due to the increased distance between fluorophore and
      quencher. We used real-time PCR equipment for capturing the signal. With this
      assay, under optimized conditions, the entire process can be completed within 1
      h. In addition, the proposed system exhibited a good selectivity for OTA against
      other mycotoxins (ochratoxin B and aflatoxin M1) and limited interference from
      aflatoxin B1 and patulin. A wide linear detection range (0.2-2000 uM) was
      achieved, with LOD = 13 nM, r = 0.9952, and R2 = 0.9904. The aptabeacon was also
      applied to detect OTA in red wine spiked with the same dilution series. A linear
      correlation with a LOD = 19 nM, r = 0.9843, and R2 = 0.9708 was observed, with
      recoveries in the range 63%-105%. Intra- and inter-day assays confirmed its
      reproducibility. The proposed biosensor, although still being finalized, might
      significantly facilitate the quantitative detection of OTA in wine samples, thus
      improving their quality control from a food safety perspective. 

PMID- 25760082
TI  - No turnover in lens lipids for the entire human lifespan.
AB  - Lipids are critical to cellular function and it is generally accepted that lipid
      turnover is rapid and dysregulation in turnover results in disease (Dawidowicz
      1987; Phillips et al., 2009; Liu et al., 2013). In this study, we present an
      intriguing counter-example by demonstrating that in the center of the human
      ocular lens, there is no lipid turnover in fiber cells during the entire human
      lifespan. This discovery, combined with prior demonstration of pronounced changes
      in the lens lipid composition over a lifetime (Hughes et al., 2012), suggests
      that some lipid classes break down in the body over several decades, whereas
      others are stable. Such substantial changes in lens cell membranes may play a
      role in the genesis of age-related eye disorders. Whether long-lived lipids are
      present in other tissues is not yet known, but this may prove to be important in
      understanding the development of age-related diseases. 

PMID- 25760081
TI  - Decoding a neural circuit controlling global animal state in C. elegans.
AB  - Brains organize behavior and physiology to optimize the response to threats or
      opportunities. We dissect how 21% O2, an indicator of surface exposure,
      reprograms C. elegans' global state, inducing sustained locomotory arousal and
      altering expression of neuropeptides, metabolic enzymes, and other non-neural
      genes. The URX O2-sensing neurons drive arousal at 21% O2 by tonically activating
      the RMG interneurons. Stimulating RMG is sufficient to switch behavioral state.
      Ablating the ASH, ADL, or ASK sensory neurons connected to RMG by gap junctions
      does not disrupt arousal. However, disrupting cation currents in these neurons
      curtails RMG neurosecretion and arousal. RMG signals high O2 by peptidergic
      secretion. Neuropeptide reporters reveal neural circuit state, as neurosecretion
      stimulates neuropeptide expression. Neural imaging in unrestrained animals shows
      that URX and RMG encode O2 concentration rather than behavior, while the activity
      of downstream interneurons such as AVB and AIY reflect both O2 levels and the
      behavior being executed. 

PMID- 25760085
TI  - Influence of Cytoplasmatic Folding on Mitochondrial Import.
AB  - The eukaryotic cell, with its organelle organization, represents a challenge for
      protein traffic. Contrary to what occurs in the endoplasmic reticulum,
      mitochondrial protein import is proposed to occur postranslationaly, as proteins
      are synthesized in cytoplasmic ribosomes and only then imported to the organelle.
      Because the diameter of the Tom and Tim pores is too narrow for the passage of a
      folded protein, it is assumed that polypeptides must be already in an unfolded,
      import competent, state for organelle entry. However, it has been suggested that
      mitochondria might be able to actively unfold proteins itself at the outer
      membrane. Here we discuss the influence of cytoplasmatic protein folding on
      mitochondrial import. Despite the contribution of active mitochondrial unfolding
      to protein import is not excluded, this mechanism is inconsistent with a number
      of experimental evidences. Accordingly, other alternative models for
      mitochondrial import are here discussed. Understanding the molecular constraints
      regulating this process is of crucial importance, since its failure can lead to a
      number of pathological situations. 

PMID- 25760083
TI  - 2.8 A resolution reconstruction of the Thermoplasma acidophilum 20S proteasome
      using cryo-electron microscopy.
AB  - Recent developments in detector hardware and image-processing software have
      revolutionized single particle cryo-electron microscopy (cryoEM) and led to a
      wave of near-atomic resolution (typically ~3.3 A) reconstructions. Reaching
      resolutions higher than 3 A is a prerequisite for structure-based drug design and
      for cryoEM to become widely interesting to pharmaceutical industries. We report
      here the structure of the 700 kDa Thermoplasma acidophilum 20S proteasome (T20S),
      determined at 2.8 A resolution by single-particle cryoEM. The quality of the
      reconstruction enables identifying the rotameric conformation adopted by some
      amino-acid side chains (rotamers) and resolving ordered water molecules, in
      agreement with the expectations for crystal structures at similar resolutions.
      The results described in this manuscript demonstrate that single particle cryoEM
      is capable of competing with X-ray crystallography for determination of protein
      structures of suitable quality for rational drug design. 

PMID- 25760086
TI  - Fourier Transform Infrared Spectroscopy (FTIR) as a Tool for the Identification
      and Differentiation of Pathogenic Bacteria.
AB  - Methods of human bacterial pathogen identification need to be fast, reliable,
      inexpensive, and time efficient. These requirements may be met by vibrational
      spectroscopic techniques. The method that is most often used for bacterial
      detection and identification is Fourier transform infrared spectroscopy (FTIR).
      It enables biochemical scans of whole bacterial cells or parts thereof at
      infrared frequencies (4,000-600 cm(-1)). The recorded spectra must be
      subsequently transformed in order to minimize data variability and to amplify the
      chemically-based spectral differences in order to facilitate spectra
      interpretation and analysis. In the next step, the transformed spectra are
      analyzed by data reduction tools, regression techniques, and classification
      methods. Chemometric analysis of FTIR spectra is a basic technique for
      discriminating between bacteria at the genus, species, and clonal levels.
      Examples of bacterial pathogen identification and methods of differentiation up
      to the clonal level, based on infrared spectroscopy, are presented below. 

PMID- 25760087
TI  - Biological agents in familial Mediterranean fever focusing on colchicine
      resistance and amyloidosis.
AB  - Familial Mediterranean fever (FMF) is the most common hereditary autoinflammatory
      syndrome. FMF is caused by mutations in the MEFV gene which encodes the pyrin
      protein. FMF is characterized by sporadic, paroxysmal attacks of fever and
      serosal inflammation, lasting 1-3 days. Patients may develop renal amyloidosis.
      Colchicine prevents attacks and renal amyloidosis.5% to 10% of the patients with
      FMF are resistant or intolerant to colchicine. Colchicine resistant patients may
      receive biological therapies. Anti-interleukin-1 drugs are the most important
      agents of biological treatments. In this review, colchicine resistance and
      treatment options will be evaluated. 

PMID- 25760084
TI  - Cytotoxic activities of CD8+ T cells collaborate with macrophages to protect
      against blood-stage murine malaria.
AB  - The protective immunity afforded by CD8(+) T cells against blood-stage malaria
      remains controversial because no MHC class I molecules are displayed on parasite
      infected human erythrocytes. We recently reported that rodent malaria parasites
      infect erythroblasts that express major histocompatibility complex (MHC) class I
      antigens, which are recognized by CD8(+) T cells. In this study, we demonstrate
      that the cytotoxic activity of CD8(+) T cells contributes to the protection of
      mice against blood-stage malaria in a Fas ligand (FasL)-dependent manner.
      Erythroblasts infected with malarial parasites express the death receptor Fas.
      CD8(+) T cells induce the externalization of phosphatidylserine (PS) on the
      infected erythroblasts in a cell-to-cell contact-dependent manner. PS enhances
      the engulfment of the infected erythroid cells by phagocytes. As a PS receptor, T
      cell immunoglobulin-domain and mucin-domain-containing molecule 4 (Tim-4)
      contributes to the phagocytosis of malaria-parasite-infected cells. Our findings
      provide insight into the molecular mechanisms underlying the protective immunity
      exerted by CD8(+) T cells in collaboration with phagocytes. 

PMID- 25760088
TI  - Human eosinophils - potential pharmacological model applied in human histamine H4
      receptor research.
AB  - Histamine and histamine receptors are well known for their immunomodulatory role
      in inflammation. In this review we describe the role of histamine and histamine
      H4 receptor on human eosinophils. In the first part of article we provide short
      summary of histamine and histamine receptors role in physiology and histamine
      related therapeutics used in clinics. We briefly describe the human histamine
      receptor H4 and its ligands, as well as human eosinophils. In the second part of
      the review we provide detailed description of known histamine effects on
      eosinophils including: intracellular calcium concentration flux, actin
      polymerization, cellular shape change, upregulation of adhesion proteins and
      cellular chemotaxis. We provide proofs that these effects are mainly connected
      with the activation of histamine H4 receptor. When examining experimental data we
      discuss the controversial results and limitations of the studies performed on
      isolated eosinophils. In conclusion we believe that studies on histamine H4
      receptor on human eosinophils can provide interesting new biomarkers that can be
      used in clinical studies of histamine receptors, that in future might result in
      the development of new strategies in the treatment of chronic inflammatory
      conditions like asthma or allergy, in which eosinophils are involved. 

PMID- 25760089
TI  - Iron Oxide Nanoparticles: An Insight into their Biomedical Applications
AB  - Iron oxide nanoparticles (IONs) are among the most common types of nanoparticles
      (NPs) used in biomedical applications. IONs can be presented in different forms
      [e.g. magnetite (Fe3O4), hematite (alpha-Fe2O3) and maghemite (gamma- Fe2O3)],
      and are usually coated with substances and/or polymers according to the purpose
      for which they are intended to be used. In recent years, IONs use has been
      increasing exponentially in many fields of biomedicine, namely in magnetic
      resonance imaging, cell sorting, tissue repair, induction of hyperthermia and
      drug delivery, among others. This review aims to provide an update on the
      different IONs and the substances and/or polymers that can be used to coat the
      IONs core as well as their applications and biological properties, namely their
      biodistribution in the human body and their cellular internalization pathways.

PMID- 25760090
TI  - The atherosclerotic plaque vulnerability: focus on the oxidative and endoplasmic
      reticulum stress in orchestrating the macrophage apoptosis in the formation of
      the necrotic core.
AB  - Although the understanding the pathophysiology of atherogenesis and
      atherosclerosis progression has been one of the major goals of cardiovascular
      research during the last decades, the precise mechanisms underlying plaque
      destabilization are still unknown. The disruption of the plaque and the
      thrombosis in the lumen that are mostly determined by the expansion of the
      necrotic core (NC) are driven by various mechanisms, including accelerated
      macrophage apoptosis and defective phagocytic clearance (defective
      efferocytosis). Oxidative stress is implicated in the expansion of the NC: in
      fact, many oxidized compounds and processes contribute to the macrophage
      apoptosis; in addition, the oxidized derivatives of polyunsatured fatty acids
      promote defective efferocytosis, with the final result of NC expansion. In the
      last years the role of the endoplasmic reticulum (ER) stress is under
      investigation to better define its possible contribution in affecting the NC
      expansion. The abnormal amount of apoptotic cells in the vulnerable plaque has
      been demonstrated to be related both to the sustained ER stress and to the
      expression of survival and protective genes, such as the unfolded protein
      response or/and the nuclear erytroid- related factor 2. In this review the
      authors focus on the promising results of the oxidative and ER stress in
      contributing to triggering and orchestrating the atherosclerotic plaque
      vulnerability. 

PMID- 25760092
TI  - Antimicrobial peptides as an opportunity against bacterial diseases.
AB  - Antimicrobial peptides (AMPs) are an heterogeneous group of small amino acidic
      molecules produced by the innate immune system of a variety of organisms
      encompassing all orders of life from eukaryotes to amphibians, insects and
      plants. Numerous AMPs have been isolated from natural sources and many others
      have been de novo designed and synthetically produced. AMPs have antimicrobial
      activity in the micromolar range and compared with traditional antibiotics, they
      kill bacteria very rapidly. They act, principally, by the electrostatic
      attraction to negatively charged bacterial cells and consequently membrane
      disruption, but their antibacterial activity may also involve interference with
      metabolic processes or different cytoplasmic targets. AMPs are a group of unique
      and incredible compounds that may be directed to a therapeutic use either alone
      or in combination with existing antibiotics. 

PMID- 25760091
TI  - The Allosteric Site for the Nascent Cell Wall in Penicillin-Binding Protein 2a:
      An Achilles' Heel of Methicillin-Resistant Staphylococcus aureus.
AB  - The ability to resist the effect of a wide range of antibiotics makes methicillin
      resistant Staphylococcus aureus (MRSA) a leading global human pathogen. A key
      determinant of resistance to beta-lactam antibiotics in this organism is
      penicillin-binding protein 2a (PBP2a), an enzyme that catalyzes the crosslinking
      reaction between two adjacent peptide stems during the peptidoglycan
      biosynthesis. The recently published crystal structure of the complex of PBP2a
      with ceftaroline, a cephalosporin antibiotic that shows efficacy against MRSA,
      has revealed the allosteric site at 60-A distance from the transpeptidase domain.
      Binding of ceftaroline to the allosteric site of PBP2a triggers conformational
      changes that lead to the opening of the active site from a closed conformation,
      where a second molecule of ceftaroline binds to give inhibition of the enzyme.
      The discovery of allostery in MRSA remains the only known example of such
      regulation of cellwall biosynthesis and represents a new paradigm in fighting
      MRSA. This review summarizes the present knowledge of the allosteric mechanism,
      the conformational changes allowing PBP2a catalysis and the means by which some
      clinical strains have acquired resistance to ceftaroline by disrupting the
      allosteric mechanism. 

PMID- 25760093
TI  - Stem cells derived from human first-trimester umbilical cord have the potential
      to differentiate into oocyte-like cells in vitro.
AB  - Compared to stem cells derived from human term umbilical cord, stem cells derived
      from human first-trimester umbilical cord (hFTUC) exhibit a significantly greater
      proliferative potential, and more efficiency in terms of their in vitro
      differentiation. In the present study, we investigated whether hFTUC-derived stem
      cells are able to differentiate into germ cells. The hFTUC-derived stem cells
      were first isolated, expanded and then cultured in differentiation medium
      containing human follicular fluid, follicle-stimulating hormone (FSH)/luteinizing
      hormone (LH) and estradiol for 24 days. During the period of induction, a
      subpopulation of the cultured cells appeared that had a morphological resemblance
      to primordial germ cells (PGCs) and cumulus-oocyte complex (COC)-like cells, and
      oocyte-like cells (OLCs). The PGC-like cells expressed specific markers
      indicative of germ cell formation such as octamer-binding transcription factor 4
      (OCT4), stage-specific embryonic antigen 1 (SSEA1), B lymphocyte-induced
      maturation protein-1 (Blimp1), PR domain containing 14 (Prdm14), transcription
      factor AP-2 gamma (Tfap2C), VASA, STELLA, deleted in azoospermia-like (DAZL) and
      interferon-induced transmembrane protein 3 (IFITM3). The OLCs, which contained a
      single germinal vesicle, expressed oocyte-specific markers, such as synaptonemal
      complex protein 3 (SCP3), growth/differentiation factor-9 (GDF9), GDF9B and zona
      pellucida (ZP)1, ZP2 and ZP3. The COC-like cells secreted estradiol, vascular
      endothelial growth factor and leukemia inhibitory factor. Thus, our findings
      suggest that hFTUC-derived stem cells have an intrinsic ability to differentiate
      into OLCs, which may provide an in vitro model for the identification of factors
      involved in germ cell formation and differentiation.

PMID- 25760094
TI  - Synergy of BID with doxorubicin in the killing of cancer cells.
AB  - Overexpression of the BH3-interacting domain death agonist (BID) protein
      sensitizes certain cancer cell lines to apoptosis induced by anticancer agents,
      particularly by those acting through death receptors (e.g. TRAIL). Previously, we
      showed that recombinant BID fused with TAT cell penetrating peptide (TAT-BID)
      allowed for controlled delivery of BID to different cancer cell lines and
      moderately sensitized some of them to TRAIL or slightly to camptothecin. In the
      present study, we showed that TAT-BID delivered to HeLa cells strongly sensitized
      them to doxorubicin, as identified by cell viability and apoptosis assays.
      Another cell line sensitized to doxorubicin was PC3, whereas A549 and LNCaP cells
      were sensitized moderately or not at all, respectively. Sensitization was more
      pronounced at 1 uM doxorubicin administered for 48 h than for lower doses and
      shorter treatments. TAT-BID and doxorubicin may thus be considered as a potential
      therapeutic combination for cervical carcinoma and advanced prostate cancer
      treatment.

PMID- 25760095
TI  - In-depth mapping of human testicular and epididymal proteins and their functional
      association with spermatozoa.
AB  - The mammalian testis and epididymis are responsible for spermatozoa production
      and maturation, which contributes to male fertility. Predominantly expressed
      proteins in the testis and epididymis were suggested to be involved in the key
      functions or pathways in spermatogenesis and sperm maturation. To further
      investigate these proteins and their associations with sperm, large protein
      profiles of human testis and epididymis were mapped. Predominantly-expressed
      testicular (173) and epididymal (244) secreted proteins were further screened and
      functionally characterized. Differential expression levels of solute carrier
      family 2 (facilitated glucose transporter), member 3, solute carrier family 25
      (carnitine/acylcarnitine translocase), member 20, WAP-type four-disulfide core
      domain protein 8 and prostate and testis expressed 1 were validated using western
      blot and immunohistochemical analyses. The results may provide novel insight into
      the understanding of testicular and epididymal physiology and function, and
      facilitate sperm maturation research.

PMID- 25760096
TI  - Paclitaxel resistance in MCF-7/PTX cells is reversed by paeonol through
      suppression of the SET/phosphatidylinositol 3-kinase/Akt pathway.
AB  - Breast cancer is one of the most prevalent types of malignant tumor. Paclitaxel
      is widely used in the treatment of breast cancer; however, the major problem
      contributing to the failure of chemotherapy in breast cancer is the development
      of drug resistance. Therefore, it is necessary to identify novel therapeutic
      targets and reversal agents for breast cancer. In the present study, the protein
      expression levels of SET, protein phosphatase 2A (PP2A) and phosphatidylinositol
      3-kinase (PI3K)/Akt pathway were determined in MCF-7/PTX human breast carcinoma
      paclitaxel-resistant cells using western blot analysis. Small interference RNAs
      (siRNAs) were used to knock down the gene expression of SET in MCF-7/PTX cells
      and the cell viability was assessed following treatment with paclitaxel, using 3
      (4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assays and flow
      cytometry. In addition, western blot analysis was used to determined PI3K/Akt
      pathway activity following SET knockdown. Furthermore, the reversal effects of
      paeonol on paclitaxel, and its underlying mechanisms of action, were investigated
      using western blot analysis and reverse transcription-quantitative polymerase
      chain reaction. The results demonstrated that increased levels of SET and
      PI3K/Akt pathway proteins were present in the MCF-7/PTX cells, compared with
      normal MCF-7 cells. Knockdown of SET significantly sensitized MCF-7/PTX cells to
      paclitaxel and induced cell apoptosis. In addition, the expression levels of the
      adenosine triphosphate binding cassette (ABC) transporter proteins were
      significantly reduced in the MCF-7/PTX cells compared with the normal MCF-7
      cells. SET-induced paclitaxel resistance was found to be associated with the
      activation of the PI3K/Akt pathway. Paeonol significantly reduced the mRNA and
      protein expression levels of SET in the MCF-7/PTX cells. Furthermore, paeonol
      significantly sensitized the MCF-7/PTX to paclitaxel via regulation of ABC
      transporters, B cell lymphoma-2 (Bcl-2) and Bcl-2-associated X protein. In
      addition, paeonol inhibited SET-mediated paclitaxel resistance by attenuating
      PI3K/Akt pathway activity in the MCF-7/PTX cells. In conclusion, the results of
      the present study demonstrated that SET was associated with paclitaxel resistance
      in MCF-7/PTX cells, and that paeonol reversed paclitaxel resistance in MCF-7/PTX
      cells by downregulating the activity of the SET/PP2A/Akt pathway.

PMID- 25760097
TI  - Parental Bonding and Body Mass Index in a Female Community Sample: The Mediating
      Role of Eating Disorder Thoughts and Core Beliefs.
AB  - BACKGROUND: It is likely that disrupted early parent-child relationships, eating
      disorder related cognitions and negative self-beliefs are relevant to some women
      who are overweight/obese. AIMS: This study tested the hypotheses that disrupted
      parent-child relationships would be linked to higher body mass index (BMI) and
      that this relationship would then be mediated by cognition. METHOD: A group of
      women were recruited from the community and completed measures of eating disorder
      (ED) thoughts, negative self-beliefs, and parental bonding. Individual body mass
      indices (BMIs) were calculated. RESULTS: One hundred and eighteen women completed
      the study. There was a relationship between parental bonding and higher BMI. As
      hypothesized, the relationship between parental bonding (as measured by maternal
      care, and paternal overprotection) and BMI appeared to be mediated by a range of
      ED thoughts, and some negative self-beliefs. CONCLUSION: The cognitions measured
      here, both ED related cognitions and negative self-beliefs, may be a useful
      target when considering psychological treatment for women who are overweight or
      obese.

PMID- 25760098
TI  - [Consistency and Reliability of MDK Expertise Examining the Encoding in the
      German DRG System].
AB  - INTRODUCTION: Hospital inpatient stays are reimbursed on the basis of German
      diagnosis-related groups (G-DRG). The G-DRG classification system is based on
      complex coding guidelines. The Medical Review Board of the Statutory Health
      Insurance Funds (MDK) examines the encoding by hospitals and delivers individual
      expertises on behalf of the German statutory health insurance companies in cases
      in which irregularities are suspected. A study was conducted on the inter-rater
      reliability of the MDK expertises regarding the scope of the assessment. METHODS:
      A representative sample of 212 MDK expertises was taken from a selected pool of 1
      392 MDK expertises in May 2013. This representative sample underwent a double
      examination by 2 independent MDK experts using a special software based on the
      3MTM G-DRG Grouper 2013 of 3M Medica, Germany. The following items encoded by the
      hospitals were examined: DRG, principal diagnosis, secondary diagnoses,
      procedures and additional payments. It was analysed whether the results of MDK
      expertises were consistent, reliable and correct. RESULTS: 202 expertises were
      eligible for evaluation, containing a total of 254 questions regarding one or
      more of the 5 items encoded by hospitals. The double-examination by 2 independent
      MDK experts showed matching results in 187 questions (73.6%) meaning they had
      been examined consistently and correctly. 59 questions (23.2%) did not show
      matching results, nevertheless they had been examined correctly regarding the
      scope of the assessment. None of the principal diagnoses was significantly
      affected by inconsistent or wrong judgment. CONCLUSION: A representative sample
      of MDK expertises examining the DRG encoding by hospitals showed a very high
      percentage of correct examination by the MDK experts. Identical MDK expertises
      cannot be achieved in all cases due to the scope of the assessment. Further
      improvement and simplification of codes and coding guidelines are required to
      reduce the scope of assessment with regard to correct DRG encoding and its
      examination.

PMID- 25760099
TI  - [Market Concentration in the Statutory Health Insurance of Germany since the
      Introduction of Free Choice of Sickness Funds].
AB  - Background: The expansion of trust law to the German statutory health insurance
      (SHI) and the declining numbers of sickness funds suggest a strong concentration
      process in the German SHI market. The paper examines the level and development of
      market concentration since the introduction of the free choice of sickness funds
      in 1996. Data: The study is based on a dataset containing information on
      membership, contribution rate, openness, area of activity and legal successor for
      all sickness funds in the period from 1996 to 2013. Methods: Market concentration
      is measured by the concentration rate (cumulative market share of the largest
      market participants) and the Herfindahl-Hirschman index (HHI). In addition, the
      change in the HHI is also disaggregated into 3 factors: opening, switching and
      fusion of sickness funds. Results: Concentration rate and HHI decreased
      significantly between 1996 and 2008 due to opening of former closed sickness
      funds and a switching behaviour from large to small funds. The SHI Competition
      Enhancement Act of 2007 led to a turnaround. The reform permitted cross-type
      mergers and introduced a completely new system of budget allocation with the
      central health fund. The latter put an end to the growing membership of small
      funds due to adverse selection processes. As a result, market concentration in
      the German SHI rises. Although recent mega-mergers were uncritical for nationwide
      competition, the study already indicates the risk of market dominance on the
      regional level.

PMID- 25760100
TI  - [Social Differences in Physical Activity among Adolescents in Germany: Analyses
      Based on Information Concerning the Metabolic Equivalent of Task (MET)].
AB  - Introduction: Energy consumption, i. e., the metabolic equivalent of task (MET),
      provides a precise assessment of physical activity (PA). Studies on social
      inequalities of PA have hardly used this possibility, however. Methods: The
      analyses are based on the 'Motorik-Modul (MoMo) of the KiGGS study (German Health
      Interview and Examination Survey for Children and Adolescents) conducted between
      2003 and 2006 (n=1 757; age group 11-17 years). PA has been assessed in 3
      settings (sport club in school, other sport club, leisure time). 3 dependent
      variables were distinguished by combining the following criteria: at least 21 MET
      hours per week, intensity between 3 and 6 METs, at least 7 hours a week. The main
      independent variables are: type of school and socioeconomic status (SES) of the
      parents. 'Two part models' have been used to assess social difference in PA among
      those who are physically active. Results: PA is much more common in the higher
      SES groups. Looking at the MET-hours, though, there are just little differences
      among those who are physically active (regressions coefficient for low vs. high
      SES: 1.15; 95% conf. interv. 0.99-1.33). Conclusion: Social differences can be
      seen mainly for the proportion of adolescents being physically active, not for
      the extent of PA among those who are physically active. Therefore, the central
      request should be to increase the proportion of adolescents performing any PA in
      the low SES group.

PMID- 25760101
TI  - [Projection of General Practitioner Care Demand at the Community Level].
AB  - BACKGROUND: Within the next 8 years about 2 000 general practitioners (GPs) will
      be seeking a successor in the federal state of Baden-Wurttemberg, Germany. Both
      the small number of newly qualified GPs and the wish to work as an employee or in
      a group practice will lead to a situation in which about 500 practices will
      likely not find a successor. Using a single administrative district, the aim of
      this analysis was to develop a projection of the demand for GP health care at the
      community level. METHODS: Using the administrative district of Rottweil with its
      21 communities, a community-based demographic forecast on the basis of current
      birth and death probabilities was performed. From the projected population
      structure, the demand for GP care in the year 2023 was derived under the
      assumption of unchanged age- and gender-specific numbers of GP visits. The
      anticipated deficit or, respectively, overrun of GPs at the community level was
      calculated as the difference between expected demand and number of GPs not
      retiring for age-related reasons. RESULTS: Until the year 2023 the demographic
      change will cause a shrinking population. However, with unchanged age- and gender
      specific numbers of GP visits, a slightly higher demand of 0.6 GPs will occur as
      a result of population-aging. The expected age-related retirement of physicians
      will have a stronger impact on primary care demand than demography. Up to 32
      (37%) GPs might need a successor. In addition to 4 communities today, this would
      result in another 5 communities not having a GP in 10 years. CONCLUSION:
      Communities that are at higher risk of GP shortage based on demographic changes
      and age of practicing GPs, can be identified by the approach described and
      applied here in order to implement targeted comprehensive community models of
      care.

PMID- 25760102
TI  - [Psychosocial working conditions and mental health status of the German
      babyboomer generation].
AB  - BACKGROUND: The baby boomers are the first to be available to the German labour
      market up to the age of 67. A crucial premise for a long working life is good
      health. However, there is evidence that psychosocial working conditions are
      related to health. More and more employees report psychosocial stress at work. In
      addition, mental illness has become one of the main reasons for the entry into
      disability pension. Against this background this study considers the relationship
      between psychosocial work conditions and mental health exemplarily for two birth
      cohorts of the German baby boomers. METHODS: For the analysis of the assumed
      relationships data of the lidA study "lidA - leben in der Arbeit - German Cohort
      Study on Work, Age and Health" is used (N=6 057). Mental health is assessed by
      the mental health scale of the SF-12. In addition, the items and the scales
      quantitative job requirements, work pace and support from colleagues from the
      Copenhagen Psychosocial Questionnaire (COPSOQ) are used. As further control
      variables cohort affiliation, level of education, occupational status and
      partnership are considered. RESULTS: Multivariate analyses of the relations
      between quantitative job requirements, work pace and the experienced support from
      colleagues show significant relationship to mental health. The increasing
      frequency of the requirement to work quickly and increasing quantitative job
      demands are negatively associated to mental health. However, support of
      colleagues shows a positive relationship to mental health. These results are
      similarly observed for women and men. CONCLUSION: For the regarded group of the
      German babyboomers, employees at the threshold to higher working age, it is
      clearly shown that psychosocial working conditions are related to mental health.
      Since this group still has to work up to 18 years given a statutory retirement
      age of 67, psychosocial working conditions should rather be in the focus of
      occupational safety.

PMID- 25760104
TI  - Advances in Brazilian public health surveillance.

PMID- 25760103
TI  - Arg972 insulin receptor substrate-1 enhances tumor necrosis factor-alpha-induced
      apoptosis in osteoblasts.
AB  - The presence of Arg972 insulin receptor substrate-1 (IRS-1) is associated with
      impaired insulin/IRS-1 signaling to activate phosphatidylinositol-3 kinase
      (PI3K). Tumor necrosis factor-alpha (TNF-alpha), an inflammatory cytokine with a
      central role in the pathogenesis of rheumatoid arthritis (RA), induces apoptosis
      in osteoblasts, which are the principal cell type responsible for bone loss in
      RA. In our previous study, an association between Arg972 IRS-1 and a high risk
      and severity of RA was identified. In the present study, the effects of Arg972
      IRS-1 and IRS-1 on TNF-alpha-induced apoptosis in human osteoblasts were
      examined. Normal and RA osteoblasts were stably transfected with Arg972 IRS-1 and
      IRS-1. In addition, cells were stably transduced with IRS-1-shRNA to knock down
      IRS1. Following stimulation with 10 nM insulin for 30 min, the stable
      overexpression of Arg972 IRS-1 and knock down of IRS-1 significantly decreased
      IRS-1-associated PI3K activity and Akt activation/phosphorylation at serine 473
      (ser473) and enhanced TNF-alpha-induced apoptosis in normal and in RA
      osteoblasts. By contrast, the stable overexpression of IRS-1 significantly
      increased the levels of IRS-1-associated PI3K activity and Akt phosphorylation
      (ser473) and inhibited TNF-alpha-induced apoptosis, which was eliminated by
      pretreatment with 50 un BJM120, a selective PI3K inhibitor, for 30 min. In
      conclusion, the present study provided the first evidence, to the best of our
      knowledge, that insulin stimulation of Arg972 IRS-1 and IRS-1 enhanced and
      inhibited TNF-alpha-induced apoptosis, respectively in normal and RA osteoblasts
      by a PI3K-dependent mechanism. These findings suggest that insulin/IRS-1
      signaling is important in the pathogenesis of RA.

PMID- 25760105
TI  - Smoking trend indicators in Brazilian capitals, 2006-2013.
AB  - This study aims to analyze the trend of indicators related to smoking in the
      capitals of Brazil from 2006 to 2013. Information on smoking trends extracted
      from the survey of risk and protective factors for chronic non-communicable
      diseases (NCDs) are analyzed through telephone interviews - VIGITEL conducted
      from 2006-2013 for the adult population in Brazilian capitals. To estimate the
      trend, the simple linear regression model was used. The prevalence of smokers in
      Brazil showed a relative reduction of 0.62% for each year of the survey, ranging
      from 15.6% in 2006 to 11.3% in 2013. A decrease was observed in both sexes in all
      age ranges except between 55 and 64 years in all education levels and regions.
      The total population of former smokers remained stable, with a reduction for men.
      Smoking 20 or more cigarettes per day decreased from 4.6% (2006) to 3.4% (2013),
      or 0.162 percentage points per year. Passive smoking at home decreased among
      women 13.4% (2009) to 10.7% (2013), a reduction of 0.72% per annum. Passive
      smoking at work has remained stable over the period. The smoking trend reduced in
      the period in most indicators, reflecting the importance of the tobacco control
      actions in the country. 

PMID- 25760106
TI  - Trends in premature mortality due to chronic non-communicable diseases in
      Brazilian federal units.
AB  - Chronic non-communicable diseases (NCDs) have a high mortality rate, mainly in
      lower and middle income countries. The major groups are cardiovascular disease
      (CVD), chronic respiratory disease (CRD), cancer and diabetes. The Action Plan to
      reduce NCDs in Brazil, 2011-2022 established a 2% yearly reduction in the NCD
      premature mortality rate as a goal. The aim of the study was to analyze trends in
      premature mortality rates and also show goal achievement scenarios for each
      Federal Unit (FU). A time series analysis of the standardized mortality rate
      between 2000-2011 was performed using the linear regression model. The average
      annual rate of increase and the 95% confidence interval were estimated. Each FU
      was classified as being likely or unlikely to achieve the goal. The FUs likely to
      achieve the goal were: for CVD - Federal District, Santa Catarina, Mato Grosso,
      Rio Grande do Sul, Minas Gerais, Bahia, Espirito Santo and Parana states; for CRD
      - Amazonas, Federal District and Parana. For neoplasms and diabetes, none of the
      FUs are likely to achieve the goal. The articulation of the three levels of
      government will allow the strengthening of interventions to reduce the
      determinants of NCDs and to improve access and quality in health care.

PMID- 25760107
TI  - Violence against children: an analysis of mandatory reporting of violence, Brazil
      2011.
AB  - This article aims to describe and analyze reporting of violence against children
      from 0 to 9 years of age, issued by the public health services, in Brazil. Data
      from the Violence and Accident Surveillance System (Viva-SINAN) were used. The
      frequency of selected variables was calculated by age group (0-1; 2-5 and 6-9
      years of age) as well as their Prevalence Ratios (PR). 17.900 cases were
      reported: 33% in the 0-1 year group; 35,8% in the 2-5 year group; and 31,2% in
      the 6-9 year group. Physical violence predominated among boys (PR: 1.22; CI 95%:
      1,16-1,28 ); 6-9 years old (PR: 1,19; CI 95%: 1,12-1.27 ). Sexual violence
      predominated among girls, mulatto/afro-descendant (PR: 1.12; CI 95 %: 1.06 to
      1.19 ); 6-9 years (PR: 4.63; CI 95%: 4.22- 5.08) with more chances of occurring
      at home (PR: 1.38 , CI: 95%: 1.29-1.48); psychological violence prevailed among
      girls, mulatto/afro-descendant (PR: 1.10; CI 95 %: 1.03-1.18 ), 6-9 years old
      (PR: 2.95; CI 95%: 2.69- 3.23), at home (PR: 1.40; CI 95%: 1.29-1.53); negligence
      predominated among boys (PR: 1.33 ; 95% CI: 1.27-1.39); 0-1 years and their
      parents were the most prevalent perpetrators.The results indicate the need to
      strengthen intersectoral actions aiming at extending the social protection and
      care network.

PMID- 25760108
TI  - Emergency room visits for work-related injuries: characteristics and associated
      factors - capitals and the Federal District, Brazil, 2011.
AB  - Work-related injuries, often classified as occupational injuries (OI), stand out
      among visits due to external causes (accidents and violence) in health services.
      To describe the characteristics and factors associated with emergency room visits
      for OI, a cross-sectional study was conducted using data from the Survey of
      Violence and Injuries in Emergency Services (VIVA Inquerito 2011) in 24 state
      capitals and the Federal District. The prevalence of treatment for OI and
      prevalence ratios (PR) with confidence intervals of 95% (95%CI) were calculated.
      There were 29,463 emergency room visits due to accidental injuries in the
      population above 18 years of age. The prevalence of OI was 33.4% and was
      positively and significantly associated with the male gender, age 30-59 years
      old, industrial workers, agricultural sector or repair and maintenance services.
      The occurrence of OI was significantly higher in attendance for objects falling
      on people (PR = 3.37, 95% CI 2.80 to 4.05) and injuries due to perforating object
      (PR = 3.01, 95% CI 2.50-3.65). The results support the surveillance of external
      causes and direct public policies to promote occupational health.

PMID- 25760109
TI  - Chronic non-communicable diseases, risk and health promotion: social construction
      of VIGITEL participants.
AB  - The dimension of choice and adherence to healthy lifestyles is in the area of
      social constructions made in representations of individuals and had not yet been
      included in the Surveillance of Risk and Protective Factors for Chronic Diseases
      by Telephone Survey (VIGITEL) analysis systems. This article aims to understand,
      in individual narratives, representations contained in the trajectories of
      people's lives selected from the 2010 VIGITEL sample, in Belo Horizonte, Minas
      Gerais. It is a qualitative study based on Social Representation Theory. Thirty
      in-depth and open interviews with subjects selected from the 2010 VIGITEL sample
      were conducted in Belo Horizonte in the State of Minas Gerais. The Structural
      Analysis of Narrative technique was used to reveal the content of speeches. Age
      and heredity representations related to NCDs are part of the spectrum of current
      scientific information. Learning from childhood onwards is the basis of care. The
      lack of comprehension of the pathophysiology of NCDs, and the depth of
      representations of illness and death related to communicable diseases, is partly
      responsible for the difficulty of preventing NCDs.

PMID- 25760110
TI  - Hospitalizations due to self-inflicted injuries - Brazil, 2002 to 2013.
AB  - The scope of this article is to describe hospitalizations resulting from
      intentionally self-inflicted injuries attended by the Unified Health System (SUS)
      for the 2002-2013 period. It is an observational, descriptive study of hospital
      admissions in the SUS arising from intentionally self-inflicted injuries in
      Brazil between 2002 and 2013. A decreasing trend was observed for the rate of
      hospitalization in individuals aged 10 and above. Hospitalizations were
      concentrated between 30 to 49 years of age for men, while for women it was
      between 20 to 29 years of age. The highest rates of hospitalization and hospital
      deaths were in the Southeast. The main cause of hospitalization was intentional
      intoxication with medication and unspecified biological substances. Studies of
      this type provide input for defining prevention strategies taking into
      consideration the most vulnerable groups and the complexity of factors associated
      with suicidal behavior. 

PMID- 25760111
TI  - Elderly patients attended in emergency health services in Brazil: a study for
      victims of falls and traffic accidents.
AB  - The article aims to describe the profile of elderly victims of falls and traffic
      accidents from the data of the Surveillance Survey of Violence and Accidents
      (VIVA). The VIVA Survey was conducted in the emergency health-services of the
      Unified Health System in the capitals of Brazil in 2011. The sample of elderly by
      type of accident was subjected to the two-step cluster procedure. Of the 2463
      elderly persons in question, 79.8% suffered falls and 20.2% were the victims of
      traffic accidents. The 1812 elderly who fell were grouped together into 4
      clusters: Cluster 1, in which all had disabilities; Cluster 2, all were non-white
      and falls took place in the home; Cluster 3, younger and active seniors; and
      Cluster 4, with a higher proportion of seniors 80 years old or above who were
      white. Among cases of traffic accidents, 446 seniors were grouped into two
      clusters: Cluster 1 of younger elderly, drivers or passengers; Cluster 2, with
      higher age seniors, mostly pedestrians. The main victims of falls were women with
      low schooling and unemployed; traffic accident victims were mostly younger and
      male. Complications were similar in victims of falls and traffic accidents.
      Clusters allow adoption of targeted measures of care, prevention and health
      promotion.

PMID- 25760112
TI  - Differentials in risk factors for chronic non-communicable diseases from the
      race/color standpoint.
AB  - This article aims to analyze the differences between the prevalence of risk
      factors of non-communicable chronic disease by race/color. It is a cross
      sectional study using data from a telephone survey of 45,448 adults. Prevalence
      ratios for chronic disease risk factors by race/color were calculated. After
      adjustments were made for education and income, race/color differences persisted.
      Among afro-descendant and mulatto women and mulatto men a higher prevalence ratio
      was identified of physical activity at work and physical activity at home. Afro
      descendant women and mulatto men indulged in less physical inactivity. Mulatto
      men and women showed a lower prevalence of smoking and consumption of 20
      cigarettes daily and lower consumption of fruit and vegetables. A higher
      consumption of full-fat milk with and beans was observed among afro-descendant
      and mulatto men. Afro-descendant women had a lower prevalence of drinking and
      driving. Afro-descendant women and men ate more meat with fat and afro-descendant
      men suffered more from hypertension. Differences in risk factors by race/color
      can be explained by cultural aspects, by not fully adjustable socioeconomic
      differences that determine less access to goods and less opportunities for the
      afro-descendant population. 

PMID- 25760113
TI  - Food and Nutrition Surveillance System/SISVAN: getting to know the feeding habits
      of infants under 24 months of age.
AB  - The objective of the Food and Nutrition Surveillance System (SISVAN) is to
      monitor the food intake of individuals attended by the Brazilian Unified Health
      System (SUS). The objective of this research was to identify the feeding
      practices of children under 24 months of age who were attended at Primary
      Healthcare Units (UBS), using SISVAN, and to assess the relationship with
      maternal sociodemographic profiles. A cross-sectional study was conducted in
      order to evaluate 350 children using the Food Consumption Marker Form of SISVAN,
      and maternal demographic data to identify sociodemographic profiles by
      exploratory factor analysis. Of the children assessed, 41.1% were under 6 months
      of age and 98.7% of those between 6 and 23 months had an inadequate intake. Two
      sociodemographic profiles were found: Profile 1 (mothers with lower income, less
      education, and recipients of the 'Bolsa Familia' conditional family grant
      program) associated with the consumption of water/tea, cow's milk and salty baby
      food; and Profile 2 (older mothers with many children and with a larger number of
      residents in the household) associated with breast milk consumption (p = 0.048).
      The use of SISVAN made it possible to identify that children had inadequate
      feeding practices, and Profile 1 appears to be a risk profile for weaning.

PMID- 25760114
TI  - Barriers to the involvement of the elderly in public services to promote physical
      activity.
AB  - The aim of this study was to examine the sociodemographic, health and behavioural
      characteristics related to non-participation of elderly people in activities
      offered by the program PROETI Health of Uberaba, Minas Gerais state.
      Observational study, case-control design with pairing 1:1 and sample composed of
      220 elderly 60-80 years. Binary Logistic Regression was used to identify the
      sociodemographic, health and behavioral factors associated with non-engagement of
      non-users to the program. After hierarchical analysis, the non-engagement of the
      elderly in the program activities was associated with depressive symptoms,
      insufficient physical activity in the domain of leisure and reduced self-efficacy
      for performing moderate or vigorous physical activity. The characteristics
      identified in this study should receive priority attention in the formulation of
      community programs targeted at promoting physical activity for elderly people.

PMID- 25760115
TI  - [Depression, cognitive deficit and factors associated with malnutrition in
      elderly people with cancer].
AB  - The study sought to analyze the presence of depression, cognitive function,
      nutritional status and factors associated with malnutrition in the elderly
      undergoing treatment for cancer. A cross-sectional study was conducted in a
      cancer clinic in Minas Gerais, which included the application of a
      sociodemographic and health questionnaire, assessment of depressive symptoms,
      cognitive function and nutritional status. 96 elderly people were evaluated, 50%
      of which were female and the mean age was 70.6 years. Cognitive impairment was
      identified in 39.6% and the presence of depression in 17.7%, with a higher number
      of depressive symptoms in females (p = 0,017). Moderate malnutrition or suspected
      malnutrition was diagnosed in 29.2%, severe malnutrition in 14.6% and 47.9% had a
      critical need for nutritional intervention. In multivariate analysis, functional
      impairment was independently associated with malnutrition (PR: 3.40; CI: 1.23
      9.45), the presence of two or more symptoms of nutritional impact (PR: 3.22; CI:
      10.03-10.10) and current treatment by chemotherapy (PR: 2.96; CI: 1.16-7.56). The
      elderly with cancer showed a high prevalence of malnutrition and a need for
      nutritional intervention. The assessment of depression and cognitive impairment
      should also be an integral part in addressing this group. 

PMID- 25760116
TI  - Microvascular complications in type 2 diabetes and associated factors: a
      telephone survey of self-reported morbidity.
AB  - The scope of this article is to estimate the prevalence of microvascular
      complications of self-reported type 2 diabetes and the association with
      sociodemographic characteristics, nutritional status, treatment given and time
      since diagnosis. It involved a cross-sectional study with 318 people with type 2
      diabetes living in Maringa in the State of Parana. A telephone survey of self
      reported morbidity was conducted in the months from January to June 2012. For the
      analysis descriptive statistics, univariate and multiple logistic regression were
      used. The prevalence of self-reported complications of diabetes was 53.8%, the
      most frequent being retinopathy (42.8%), followed by peripheral neuropathy
      (14.5%) and nephropathy (12.9%). The variables associated with the presence of
      complications were age (p = 0.008), overweight/obesity (p = 0.002), insulin (p <
      0.001), insulin use linked to oral antidiabetic drug (p = 0.003) and time since
      diagnosis (p = 0.013). The prevalence of self-reported microvascular
      complications for people with diabetes was high, being more frequent among those
      of more advanced age, with inadequate nutritional status, a delay in diagnosis of
      the disease and those who were using insulin alone or in combination with oral
      antidiabetic agents. 

PMID- 25760117
TI  - Exclusion and bioethics: a Brazilian perspective.
AB  - This paper discusses exclusion from the perspective of a developing country,
      namely Brazil, associating semantic peculiarities to the behavior of different
      social groups and actors and relating them to the hierarchical structure that
      shapes society. Aiming to uncover these unconscious mechanisms, the article seeks
      to elicit individual reflection on the role that each person plays in the
      maintenance of the inequities inherent to social life in this context. 

PMID- 25760118
TI  - Gender inequalities in external cause mortality in Brazil, 2010.
AB  - OBJECTIVE: To estimate mortality rate by external causes in Brazil. METHODS:
      Mortality national 2010's data corrected by underreport and adjusted by direct
      method were evaluated by sex according to age, region of residence, race/skin
      color, education and conjugal situation. RESULTS: The standardized mortality
      coefficient of external causes is higher among men (178 per thousand inhabitants)
      than among women (24 per thousand inhabitants), being higher among young men (20
      to 29 years old) in all regions and decreasing with aging. The mortality rate
      reaches almost nine times higher among men comparably to women, being higher in
      North and Northeast regions. The death incidence by external causes is higher
      among men (36.4%) than among women (10.9%), meaning 170% more risk for men. The
      risk is also higher among the youngest: 6.00 for men and 7.36 for women. The main
      kind of death by external causes among men is aggressions, followed by transport
      accidents, the opposite of women. CONCLUSIONS: Besides sex, age is the more
      important predictive factor of precocious death by external causes, pointing the
      need of many and various sectors in order to construct new identities of non
      violence.

PMID- 25760119
TI  - Physical benefits and reduction of depressive symptoms among the elderly: results
      from the Portuguese "National Walking Program".
AB  - The aim of this study was to investigate alterations in physical fitness and
      anthropometric parameters as well as depression symptoms among the elderly after
      participation in the "National Walking Program" (Portugal). The sample consisted
      of 26 elderly people over six months with a total of 72 exercise sessions. The
      exercise sessions consisted of aerobics (walking and running) and strength and
      flexibility exercises. Participants were assessed pre- and post-intervention for
      physical fitness with the Rikli & Jones test. The anthropometric measurements
      were assessed with a bioimpedance scale and a stadiometer, and depression with
      Yesavage's Geriatric Depression Scale. Physical activity was only assessed with
      an accelerometer at the pre-intervention phase. For statistical analysis, the
      student t test for paired samples was performed using SPSS 21 software.
      Statistically significant improvements were found in depressive symptoms (p <=
      0.001), and in all physical fitness tests (p <= 0.05) except for flexibility
      tests (p >= 0.05). Waist circumference reduction also showed the positive effects
      of the intervention (p = 0.031). The conclusion drawn is that participation in
      the "National Walking Program" for 6 months was effective in improving the
      physical and psychological health of the elderly.

PMID- 25760120
TI  - [Unawareness of hypertension and its determinants among 'quilombolas'
      (inhabitants of 'quilombos' - hinterland settlements founded by people of African
      origin) living in Southwest Bahia, Brazil].
AB  - This study sought to evaluate the prevalence of unawareness of arterial
      hypertension (AH) and associated factors among the quilombola population and to
      describe aspects of the non-pharmacological management of AH. It involved a cross
      sectional study with a sample of 358 people with AH aged 18 years or more. AH was
      considered systolic blood pressure (BP) >= 140 mmHg and/or diastolic blood
      pressure >= 90 mmHg and/or reported use of antihypertensive drugs. Unawareness of
      AH was classified as persons answering negatively when asked if they suffered
      from AH. Poisson regression was then used. The prevalence of unawareness of AH
      was 44.1% (95% CI: 38.9-49.3). Among those who already knew the diagnosis and had
      drug treatment only 24.8% had controlled BP. The unawareness of AH was positively
      associated with the male sex and Stage 1 of AH and negatively with increasing
      age, overweight, negative self-perception of health and medical visits. For non
      pharmacological management, low percentages of quilombola reported appropriate
      standard recommendations of care. Arterial hypertension is a serious public
      health issue among the quilombola population, revealing great vulnerability in
      health due to poor levels of awareness, treatment and control. 

PMID- 25760121
TI  - [Prevalence of moderate and excessive alcohol consumption and associated factors
      among residents of Quilombo Communities (hinterland settlements founded by people
      of African origin) of Vitoria da Conquista, Bahia, Brazil].
AB  - The scope of the study was to assess moderate and excessive alcohol consumption
      and associated factors among residents of Quilombola Communities in Vitoria da
      Conquista in the State of Bahia. It involved a cross-sectional study among 750
      individuals aged >= 18 years interviewed in 2011 using an adapted version of the
      National Survey of Health Questionnaire. Alcohol consumption was classified into
      abstemious, moderate and heavy drinking categories and was analyzed using the
      multinomial regression model. Consumption was observed among 41.5% of
      participants (95% CI [37.8, 44.98]); 10.7% being identified in the excessive
      consumption category and 30.8% in the moderate consumption category. Moderate
      consumption was inversely associated with age and is more common among whites and
      mulattoes, the better educated, the gainfully employed and among smokers. Heavy
      consumption increased with level of education, being more prevalent among those
      who had at least 8 years of schooling, smokers and the gainfully employed. The
      study shows that in these communities there are differences in the
      sociodemographic characteristics among the profiles of alcohol drinkers and these
      differences should be taken into account when drawing up proposals for the
      promotion of healthy habits. 

PMID- 25760122
TI  - [Combined nutritional indicators and associated factors in the Quilombo
      population (hinterland settlements founded by people of African origin) in
      southwestern Bahia, Brazil].
AB  - This study sought to estimate the prevalence of the combination of Body Mass
      Index (BMI) plus Waist Circumference (WC) and of BMI plus Waist to Height Ratio
      (WHR) and to investigate associated factors. A two-stage random sample of adults
      (>20 years) living in former African slaves communities (Quilombos) was taken in
      Vitoria da Conquista in the State of Bahia in 2011. Combined BMI+WHR nutritional
      risk was defined by the simultaneous presence of BMI > 25.0Kg/m2 or > 27.0Kg/m2,
      if aged > 60 years and WHR > 0.5. BMI + WC nutritional risk was defined by
      elevated BMI in addition to WC > 80cm for women, or > 94cm for men. Among the 739
      participants, the prevalence of combined nutritional indicators were 35.3% (BMI +
      WHR) and 26.8% (BMI + WC). Female sex and hypertension increased the chances of a
      combination of both indicators, while being unmarried decreased the chances. The
      prevalence of BMI + WHR was higher in the 40-59 year age range and the prevalence
      of BMI + WC was higher in the 40-49 year age range. Less schooling increased the
      chances of the combined BMI + WHR indicator and watching television for more than
      two hours/day increased the chances of the BMI + WC indicator. The high
      prevalence of combined nutritional indicators indicate the need of diet promotion
      actions to prevent obesity.

PMID- 25760123
TI  - Death in hospital and at home: population and health policy influences in
      Londrina, State of Parana, Brazil (1996-2010).
AB  - An aging population and epidemiological transition involves prolonged terminal
      illnesses and an increased demand for end-stage support in health services,
      mainly in hospitals. Changes in health care and government health policies may
      influence the death locations, making it possible to remain at home or in an
      institution. The scope of this article is to analyze death locations in the city
      of Londrina, State of Parana, from 1996 to 2010, and to verify the influence of
      population and health policy changes on these statistics. An analysis was
      conducted into death locations in Londrina in Mortality Information System (SIM)
      considering the main causes and locations of death. There was an increase of 28%
      in deaths among the population in general, though 48% for the population over 60
      years of age. There was an increase of deaths in hospitals, which were
      responsible for 70% of the occurrences, though death frequencies in others
      locations did not increase, and deaths in the home remained at about 18%. The
      locations of death did not change during this period, even with health policies
      that broadened care in other locations, such as the patient's home. The
      predominance of hospital deaths was similar to other Brazilian cities, albeit
      higher than in other countries.

PMID- 25760124
TI  - Cardiac misconceptions among healthy adults: implications for the promotion of
      health in the community.
AB  - This study sought to confirm the structure and to investigate the psychometric
      properties of an experimental Portuguese version of the York Cardiac Beliefs
      Questionnaire (YCBQ) in a general population sample. It also set out to identify
      the prevalent misconceptions in the community and to assess the differences
      according to socio-demographic characteristics. It involved a cross-sectional
      survey in which both test and validation samples were collected (n = 476),
      including participants aged between 18 and 40, recruited via e-mail and social
      networks. The Confirmatory Factor Analysis on both samples suggested a shorter,
      three factor version of the YCBQ. Also, misconceptions differed significantly
      according to sociodemographic variables. The validation of the YCBQ for samples
      in the community constitutes an important starting point to promote research on
      misconceptions held in the community by specific groups, as well as to provide
      key points for health promotion. 

PMID- 25760125
TI  - [Social support to women after mastectomy: a review study].
AB  - It is necessary to understand how social support can contribute to minimize the
      impact of the diagnosis and treatment of mammary tumors in order to underpin the
      actions of comprehensive women's health care. This study seeks to analyze the
      contribution of the national and international literature regarding the perceived
      social support by women diagnosed with breast cancer. Twelve studies were
      selected from the MedLine, Lilacs and PsycINFO databases over a 10-year period
      (2000-2010) with pre-defined criteria for inclusion. The results were organized
      into thematic categories: the perception of family support; perceived social
      support; the perception of educational support; the need to improve the research
      and the assistance given to women after mastectomy and their families. The
      studies dedicated to the subjective dimension of social support are still
      incipient. The available evidence suggests that the literature is limited to
      topics of interest to the traditional health professions, such as Nursing and
      Medicine, focusing on constructs that can be directly quantified. The concern
      with social support must be present from the time of diagnosis to psychosocial
      rehabilitation, as part of the process of tackling the situation. 

PMID- 25760126
TI  - [Health literacy in type 2 diabetics: associated factors and glycemic control].
AB  - Diabetes mellitus patients must concentrate on self-care, with complex treatments
      and adequate health behavior in which such habits are a key factor. Due to the
      complexity of this issue, the importance of literacy in health arises. The goal
      of the study was to analyze factors associated with literacy in health and its
      relation with glycemic control in diabetic patients. It involved a study with 82
      type 2 diabetic patients of both sexes and aged between 19 and 59 attended in the
      outpatient endocrinology ward of a public hospital, who filled out an abbreviated
      and translated version of the Test of Functional Health Literacy in Adults (b
      TOFHLA). Fasting glycaemia values and glycated hemoglobin were collected from the
      clinical history of the participants. Correlations, mean comparisons and linear
      regression models were tested. Inadequate literacy in health was encountered in
      65.9% of the patients. The issues involved factors associated with the b-TOFHLA
      point scores were age and years of schooling. Global literacy did not explain the
      glycemic control, but the level of numeracy presented an association with this
      control. The results point to the need to improve the numeracy in health of the
      patients to obtain enhanced glycemic control, mainly in those with more advanced
      age and less years of schooling. 

PMID- 25760127
TI  - [Impact of the activation of intention to perform physical activity in type II
      diabetics: a randomized clinical trial].
AB  - Type II diabetes mellitus is a highly prevalent disease among the adult Brazilian
      population, and one that can be controlled by interventions such as physical
      activity, among others. The aim of this randomized controlled study was to
      evaluate the impact of a traditional motivational strategy, associated with the
      activation of intention theory, on adherence to physical activity in patients
      with type II, diabetes mellitus who are part of the Unified Health System (SUS).
      Participants were divided into a control group (CG) and an intervention group
      (IG). In both groups, the traditional motivational strategy was applied, but the
      activation of intention strategy was only applied to the IG Group. After a two
      month follow-up, statistically significant differences were verified between the
      groups, related to the practice of walking (p = 0.0050), number of days per week
      (p = 0.0076), minutes per day (p = 0.0050) and minutes walking per week (p =
      0.0015). At the end of the intervention, statistically significant differences in
      abdominal circumference (p = 0.0048) between the groups were observed. The
      conclusion drawn is that the activation of intention strategy had greater impact
      on adherence to physical activity and reduction in abdominal circumference in
      type II diabetics, than traditional motivational strategy. 

PMID- 25760128
TI  - Characterization of victims of aggression and transportation accidents treated at
      the Forensic Medicine and Dentistry Institute - Campina Grande, Paraiba, Brazil -
      2010.
AB  - The objective of this cross-sectional census study was to characterize agression
      and land-based transport accidents in a city in the Northeast of Brazil. Data was
      analyzed from live victims who were treated at a forensic service (N = 2.379). In
      the descriptive analysis, the majority of events were represented by aggression
      (71.6%); which occurred on weekdays (65%), with 35.1% at night. Trauma occurred
      to the whole body (63.6%) and to soft tissue (74.2%). On the basis of multiple
      correspondence analysis, two dimensions were formed: the first dimension
      (internal reliability = 0.654) was formed by the cause of the event, the trauma
      and the age group and the second dimension (reliability = 0.514), by age group,
      occupation and civil status. Three groups with distinct profiles were formed for
      accidents and aggression: young women who suffered aggression, with trauma to the
      face and soft tissues during the evening and at weekends; adult men who suffered
      car accidents, in the morning and on work days; and retired elderly widowers, who
      were run over. 

PMID- 25760129
TI  - [Trends in mortality due to breast cancer among women in the state of Rio de
      Janeiro, Brazil, 1996-2011].
AB  - A descriptive time series study was conducted in order to analyze the mortality
      rates for breast cancer in two age brackets (< 60 years and >= 60 years), in
      areas of the state of Rio de Janeiro (inland, metropolitan area, capital and
      state). The data source was the Mortality Information System. Mortality rates
      were analyzed for four-year periods, between 1996 and 2011, and the ratios
      between the incidences for the two age brackets in each area. The trend in annual
      mortality rates was analyzed with the Joinpoint program and polynomial regression
      models. The ratios between the incidences observed were 7-8 times higher in women
      aged 60 years or older. Joinpoint analyses indicated a linear decline in
      mortality rates in the state and the capital for the whole population and for
      women aged 60 and over in the same areas. The polynomial regression models
      allowed the observation of periods of increasing and decreasing rates and a
      tendency to stabilization at the end of the period. Despite the declining trend,
      the magnitude of mortality from breast cancer is still high among women aged 60
      and older, and it is important to investigate associated factors in this
      population group. 

PMID- 25760130
TI  - Ricardo Bruno: history, social processes and health practices.
AB  - This essay has the objective of revisiting the intellectual output of Ricardo
      Bruno Mendes-Goncalves (1946-1996), Professor of the Department of Preventive
      Medicine of the Faculty of Medicine of the University of Sao Paulo and one of the
      theoreticians who participated in the construction of the field of Brazilian
      Collective Health during the years 1970-1990. On the basis of brief biographical
      and bibliographical information, as well as relevant aspects regarding the
      historical context in which his output is located, I examine the principal works
      of the author, their effects on the lines of investigation of investigation of
      his students and his legacy of contributions and challenges for Collective
      Health. I highlight the genesis and development of his Theory of the Health Work
      Process and its impact on the understanding and empirical investigation of the
      socio-historical dimensions of health practices and on the reconstruction of
      knowledge and technologies in the context of the Brazilian Health Sector Reform.
      In particular, I highlight his concern with the ethical perspective of academic
      praxis and in this sense, with hope as a human value which is historically
      objectified and intersubjectively constructed.

PMID- 25760131
TI  - [Notes for understanding the problem of "public" health in the health sector].
AB  - This paper presents a theoretical review of how the public health concept has
      been perceived in health practices, based on the problematic field introduced in
      Italian and Brazilian health reforms, in order to understand the construction of
      public health and the meanings that this term acquires in the health arena. The
      main goal is to understand how public health appears in the context of health
      movements in Italy and Brazil, as well as its movement of variation. In this
      sense, an attempt is made to identify elements that contribute to the composition
      of a genealogy of public health. From the investigation of public health
      practices, the tensions produced by this concept are analyzed, giving visibility
      to those practices that demonstrate the public health experience as a force in
      the world of health. 

PMID- 25760132
TI  - [Construction of measurement instruments in the area of health].
AB  - Measurement instruments are an integral part of clinical practice, health
      evaluation and research. These instruments are only useful and able to present
      scientifically robust results when they are developed properly and have
      appropriate psychometric properties. Despite the significant increase of rating
      scales, the literature suggests that many of them have not been adequately
      developed and validated. The scope of this study was to conduct a narrative
      review on the process of developing new measurement instruments and to present
      some tools which can be used in some stages of the development process. The steps
      described were: I-The establishment of a conceptual framework, and the definition
      of the objectives of the instrument and the population involved; II-Development
      of the items and of the response scales; III-Selection and organization of the
      items and structuring of the instrument; IV-Content validity, V-Pre-test. This
      study also included a brief discussion on the evaluation of the psychometric
      properties due to their importance for the instruments to be accepted and
      acknowledged in both scientific and clinical environments. 

PMID- 25760133
TI  - Adverse events and other incidents in neonatal intensive care units.
AB  - The occurrence of avoidable adverse events (AEs) represents a problem of quality
      of care that is responsible for the increase in monetary and social costs,
      causing suffering to the patient, their family members and the professional
      involved. This situation is aggravated when it involves newborns (NBs) with very
      low birth weights and shorter gestational ages, admitted to neonatal intensive
      care units (NICU). The scope of this study is to understand more about these
      incidents and adverse events in NICUs. The article aims to identify the
      occurrence of incidents, with and without injury that have occurred in NICUs in
      the literature and correlate this with the gestational age group of the NBs most
      affected. This is a systematic review of the available literature on incidents,
      particularly AEs as witnessed in NICUs. This study reveals that the types of
      incidents that occur in NICUs, with or without injury to the patient, are related
      to errors or failures in medication use, healthcare-associated infections (HAIs),
      skin injuries, mechanical ventilation and intravascular catheters. The cause of
      incidents and adverse events in NICUs are associated with human factors and the
      outcomes that are most damaging are due to HAIs. Furthermore, the study points
      out ways to mitigate these occurrences. 

PMID- 25760134
TI  - [Analysis of the use of data from the Primary Health Care Information System
      (SIAB): an integrative review of the literature].
AB  - This paper aimed to identify instances of the use of data from the Primary Health
      Care Information System in the existing scientific literature. This study is an
      Integrative Literature Review and the search for articles was performed in May,
      2013 in the Virtual Healthcare Library (MedLine, Lilacs and SciELO), considering
      publications from 2008 to 2012. The search for articles initially located 164
      texts, though after applying the inclusion and exclusion criteria, this review
      concentrated on 12 articles. The main results showed that there are fragilities
      like the use of the form just for the record and the insufficient training of the
      teams. However, the positive aspect is that the Primary Health Care Information
      System is the leading source of health information and statistics, and that its
      information can and must be used for health planning activities. Thus, it is an
      information system that assists municipal management and the actions in health of
      its teams, alerting the community to the need for care of individual health. 

PMID- 25760137
TI  - Metformin alleviates high glucose-mediated oxidative stress in rat glomerular
      mesangial cells by modulation of p38 mitogen-activated protein kinase expression
      in vitro.
AB  - The aim of the current study was to investigate the effects and mechanism of
      metformin in oxidative stress and p38 mitogen-activated protein kinase (p38MAPK)
      expression in rat glomerular mesangial cells (MCs) cultured in a high glucose
      medium. Rat glomerular MCs (HBZY-1) were cultured in complete medium and divided
      into the following five groups: Normal control (NC), high glucose (HG), metformin
      treated, SB203580-treated (SB) and N-acetylcysteine-treated (NAC). The production
      of intracellular reactive oxygen species (ROS) in rat glomerular MCs was measured
      using flow cytometry. Superoxide dismutase (SOD) activity and malondialdehyde
      (MDA) content in the supernatant was detected using colorimetric analysis and an
      ELISA, respectively. p22phox mRNA levels in rat glomerular MCs were determined
      using reverse transcription-quantitative polymerase chain reaction. The levels of
      p22phox protein and phosphorylated p38 mitogen-activated protein kinase (p
      p38MAPK) protein in rat glomerular MCs were determined by western blot analysis.
      Compared with the NC group, the activity of SOD in the supernatant was
      significantly reduced, whereas the levels of MDA in the supernatant,
      intracellular p22phox mRNA and protein, p-p38MAPK protein in addition to ROS
      production in rat glomerular MCs were significantly increased in the HG group
      (P<0.05). When metformin was added to the high glucose medium, the activity of
      SOD in supernatant fluid was increased significantly, whereas a significant
      reduction (P<0.05) was observed in the levels of MDA in the supernatant,
      intracellular p22phox mRNA and protein, p-p38MAPK protein in addition to ROS
      production in rat glomerular MCs. These results were similar to those obtained
      when SB203580 or N-acetylcysteine was added to the high glucose medium (P<0.05).
      In conclusion, metformin was suggested to alleviate high glucose-induced
      oxidative stress and p-p38MAPK protein expression in rat glomerular MCs, which
      may contribute to its reno-protective abilities in diabetes.

PMID- 25760138
TI  - Bismuth labeling for the CT assessment of local administration of magnetic
      nanoparticles.
AB  - Many therapeutic applications of magnetic nanoparticles involve the local
      administration of nanometric iron oxide based materials as seeds for
      magnetothermia or drug carriers. A simple and widespread way of controlling the
      process using x-ray computed tomography (CT) scanners is desirable. The
      combination of iron and bismuth in one entity will increase the atenuation of x
      rays, offering such a possibility. In order to check this possibility core-shell
      nanocrystals of iron oxide@bismuth oxide have been synthesized by an aqueous
      route and stabilized in water by polyethylene glycol (PEG), and we have evaluated
      their ability to generate contrast by CT and magnetic resonance imaging (MRI) to
      measure the radiopacity and proton relaxivities using phantoms. High-resolution
      scanning transmission electron microscopy (STEM) revealed that the material
      consists of a highly crystalline 8 nm core of maghemite and a 1 nm shell of
      bismuth atoms either isolated or clustered on the nanocrystal's surface. The
      comparison of MUCT and MRI images of mice acquired in the presence of the
      contrast shows that when local accumulations of the magnetic nanoparticles take
      place, CT images are more superior in the localization of the magnetic
      nanoparticles than MRI images, which results in magnetic field inhomogeneity
      artifacts. 

PMID- 25760139
TI  - Two year field study to evaluate the efficacy of Mamestra brassicae
      nucleopolyhedrovirus combined with proteins derived from Xestia c-nigrum
      granulovirus.
AB  - Japan has only three registered baculovirus biopesticides despite its long
      history of studies on insect viruses. High production cost is one of the main
      hindrances for practical use of baculoviruses. Enhancement of insecticidal effect
      is one possible way to overcome this problem, so there have been many attempts to
      develop additives for baculoviruses. We found that alkaline soluble proteins of
      capsules (GVPs) of Xestia c-nigrum granulovirus can increase infectivity of some
      viruses including Mamestra brassicae nucleopolyhedrovirus (MabrNPV), and
      previously reported that MabrNPV mixed with GVPs was highly infectious to three
      important noctuid pests of vegetables in the following order, Helicoverpa
      armigera, M. brassicae, and Autographa nigrisigna. In this study, small-plot
      experiments were performed to assess concentrations of MabrNPV and GVPs at three
      cabbage fields and a broccoli field for the control of M. brassicae. In the first
      experiment, addition of GVPs (10 ug/mL) to MabrNPV at 106 OBs/mL resulted in a
      significant increase in NPV infection (from 53% to 66%). In the second
      experiment, the enhancing effect of GVP on NPV infection was confirmed at 10
      times lower concentrations of MabrNPV. In the third and fourth experiments, a 50%
      reduction in GVPs (from 10 ug/mL to 5 ug/mL) did not result in a lowering of
      infectivity of the formulations containing MabrNPV at 105 OBs/mL. These results
      indicate that GVPs are promising additives for virus insecticides.

PMID- 25760140
TI  - HPV-E7 delivered by engineered exosomes elicits a protective CD8+ T cell-mediated
      immune response.
AB  - We developed an innovative strategy to induce a cytotoxic T cell (CTL) immune
      response against protein antigens of choice. It relies on the production of
      exosomes, i.e., nanovesicles spontaneously released by all cell types. We
      engineered the upload of huge amounts of protein antigens upon fusion with an
      anchoring protein (i.e., HIV-1 Nefmut), which is an inactive protein
      incorporating in exosomes at high levels also when fused with foreign proteins.
      We compared the immunogenicity of engineered exosomes uploading human
      papillomavirus (HPV)-E7 with that of lentiviral virus-like particles (VLPs)
      incorporating equivalent amounts of the same antigen. These exosomes, whose
      limiting membrane was decorated with VSV-G, i.e., an envelope protein inducing pH
      dependent endosomal fusion, proved to be as immunogenic as the cognate VLPs. It
      is noteworthy that the immunogenicity of the engineered exosomes remained
      unaltered in the absence of VSV-G. Most important, we provide evidence that the
      inoculation in mouse of exosomes uploading HPV-E7 induces production of anti-HPV
      E7 CTLs, blocks the growth of syngeneic tumor cells inoculated after
      immunization, and controls the development of tumor cells inoculated before the
      exosome challenge. These results represent the proof-of-concept about both
      feasibility and efficacy of the Nefmut-based exosome platform for the induction
      of CD8+ T cell immunity.

PMID- 25760141
TI  - Gene amplification during differentiation of mammalian neural stem cells in vitro
      and in vivo.
AB  - In development of amphibians and flies, gene amplification is one of mechanisms
      to increase gene expression. In mammalian cells, gene amplification seems to be
      restricted to tumorigenesis and acquiring of drug-resistance in cancer cells.
      Here, we report a complex gene amplification pattern in mouse neural progenitor
      cells during differentiation with approximately 10% of the genome involved. Half
      of the amplified mouse chromosome regions overlap with amplified regions
      previously reported in human neural progenitor cells, indicating conserved
      mechanisms during differentiation. Using fluorescence in situ hybridization, we
      verified the amplification in single cells of primary mouse mesencephalon E14
      (embryonic stage) neurosphere cells during differentiation. In vivo we confirmed
      gene amplifications of the TRP53 gene in cryosections from mouse embryos at stage
      E11.5. Gene amplification is not only a cancer-related mechanism but is also
      conserved in evolution, occurring during differentiation of mammalian neural stem
      cells. 

PMID- 25760142
TI  - Targeting the degradation of AXL receptor tyrosine kinase to overcome resistance
      in gefitinib-resistant non-small cell lung cancer.
AB  - Acquired resistance to epidermal growth factor receptor tyrosine kinase
      inhibitors (EGFR-TKIs), such as gefitinib, remains a major problem in non-small
      cell lung cancer (NSCLC) treatment. Increased activation of AXL has been
      identified as a novel mechanism for acquired resistance to EGFR-TKIs in NSCLC
      treatment. However, the cause of uncontrolled AXL expression is not fully
      understood. Here, we first demonstrate that AXL is overexpressed in an acquired
      gefitinib-resistant cell line (H292-Gef) as a result of slow turnover and that
      AXL is degraded by presenilin-dependent regulated intramembrane proteolysis (PS
      RIP). Based on the findings, we attempted to enhance AXL degradation to overcome
      acquired gefitinib-resistance by the treatment of gefitinib-resistant NSCLC cells
      with yuanhuadine (YD), a potent antitumor agent in NSCLC. Treatment with YD
      effectively suppressed the cancer cell survival in vitro and in vivo.
      Mechanistically, YD accelerated the turnover of AXL by PS-RIP and resulted in the
      down-regulation of the full-length AXL. Therefore, the modulation of the
      proteolytic process through degradation of overexpressed AXL may be an attractive
      therapeutic strategy for the treatment of NSCLC and EGFR-TKI-resistant NSCLC. 

PMID- 25760143
TI  - Hydroxyapatite nanoparticles modified by branched polyethylenimine are effective
      non-viral vectors for siRNA transfection of hepatoma cells in vitro.
AB  - Small interfering RNA (siRNA) technology is a powerful tool in biomedical
      research and holds great potential for RNA interference-based therapies for HIV,
      hepatitis and cancer. However, the absence of a safe and efficient method for the
      delivery of siRNA has become a bottleneck for their development. Nanocrystallized
      hydroxyapatite (nHAP) appears to be an optimal candidate non-viral gene vector
      for several reasons, including its good biocompatibility and ease of production,
      however, nHAP microemulsions cannot remain monodispersed for long periods of
      time. Due to their high surface energy, nHAP particles gradually aggregate into
      large ones that are difficult for the cell to take up. To overcome this we
      modified nHAP with polyethylenimine (PEI) to generate a compound (MnHAP) with a
      tight size-distribution of <200 nm. The positive surface potential of MnHAP
      inhibited particle aggregation and thus made it easier to conjugate more siRNA.
      The transfection efficiency of MnHAP/fluorescent FAM-labeled siRNA complex was
      tested using flow cytometry, and the transfected cells were observed using
      fluorescence microscopy. The cytotoxicity of MnHAP/siRNA complexes to the human
      liver cancer cell line BEL-7402 was assessed in vitro by a formazan dye assay.
      Our results show that the in vitro transfection efficiency of MnHAP/siRNA was
      equivalent to that of the commercially available transfection agent
      Lipofectamine(r) 2000, but with decreased cytotoxicity. The MnHAP nanoparticles
      were also able to deliver siRNA for silencing of glyceraldehyde-3-phosphate
      dehydrogenase (GAPDH) in BEL-7402 cells, which supports that MnHAP might be a
      promising non-viral vector for biomedical research and gene delivery.

PMID- 25760144
TI  - The ALDH1+ subpopulation of the human NMFH-1 cell line exhibits cancer stem-like
      characteristics.
AB  - Cancer stem cells (CSCs) have been reported in many tissues. However, CSCs have
      yet to be identified in a human malignant fibrous histiocytoma (MFH) cell line.
      Elevated aldehyde dehydrogenase 1 (ALDH1) has been proposed as a stem cell marker
      for isolating CSCs from cancer. The aim of the present study was to identify a
      population with elevated ALDH in the human NMFH-1 cell line. ALDH+ and ALDH- cell
      populations were isolated and compared for CSC characteristics. ALDH enzymatic
      activity was used as a marker to identify the cells in the NMFH-1 line. Self
      renewal, differentiation capacity, and tumorigenicity of the NMFH-1 ALDH+ cell
      population were then examined using a spheroid formation assay and xenograft
      model in nude mice. Chemoresistance levels, ABCG2 drug transport gene expression,
      and stem cell-associated gene expression were compared in these NMFH-1
      populations. The ALDH+ population was better able to form spheres in anchorage
      independent serum-starved conditions. Furthermore, the mRNA expression of key
      stem cell-related genes was enhanced in these cells. Increased expression of the
      drug transporter gene, ABCG2, was detected. Compared with ALDH-, the ALDH+
      subpopulation had higher levels of chemoresistance to doxorubicin (DXR) and
      cisplatin (CDDP). Additionally, the ALDH+ cells more efficiently formed tumors
      when implanted into BALB/c nude mice. ALDH1 may therefore be used as a marker for
      the isolation of cells that exhibit several characteristics of CSCs from the NMFH
      1 cell line. This finding may lead to the development of novel therapies to
      specifically kill ALDH1+ subpopulations (CSCs).

PMID- 25760145
TI  - A patient with unusual features and a 69.5 Mb duplication from a de novo extra
      der (9): a case report.
AB  - Partial trisomy 9 is a common autosomal trisomy, which is characterized by non
      specific psychomotor delay, mental retardation and moderately abnormal
      characteristic facial features. Generally, partial trisomy 9 leads to variable
      phenotypes depending on the size and position of the duplicated region. However,
      a precise genotype/phenotype map has not been determined. The present study
      reports the case of a 3-year-old female with certain typical features of trisomy
      9p syndrome, who presented with a number of the distinctive symptoms, as well as
      sensorineural hearing loss, which has not previously been associated with this
      trisomy. Karyotype, M-FISH and OaCGH analysis were performed on the patient and
      her parents. The final karyotype was determined to be 47, XX, +mar.ish der (9)
      (wcp9+). arr cgh 9pterq21.12 (DOCK8 -> LOC138225)x3. Cytogenetic results showed a
      de novo extra der (9) with 69.5 Mb duplication. Although the molecular mechanism
      underlying the hearing loss is unclear, it was proposed that the 9q13 -> 9q21
      region may be critical for hearing.

PMID- 25760147
TI  - A Method for Detecting the Deterioration in the Shock Absorption Capability of
      Mouthguards.
AB  - Objective methods for mechanical assessment of mouthguards used for a prolonged
      period of time are currently unavailable. The aim of this experimental study was
      to establish a quantitative method for assessing the preventive effect of
      mouthguards. 10 participants volunteered for this study. Impact loads were
      simulated by dropping a 250-g steel rod from a height of 100 mm onto upper front
      teeth of 10 custom ethylene vinyl acetate mouthguards fixed to a steel receiving
      rod. The mean output from load cells equilaterally placed between plates at the
      base of the apparatus was measured as the impact pressure (N). Its attenuation
      ratio (%) was calculated as the ratio of the difference in impact pressures
      without and with a mouthguard to impact pressure without a mouthguard. Impact
      pressure with mouthguard was approximately 60% of that without mouthguard in all
      cases. Intraclass correlations showed excellent intra-rater and inter-rater
      reliability for attenuation ratio (0.98 and 0.94, respectively). Bland-Altman
      plots indicated lack of systematic bias. The results suggest that attenuation
      ratio of impact pressure calculated by the proposed method is a valid criterion
      for assessing the preventive effect of mouthguards. The method may enable early
      detection of mouthguard deterioration and their timely replacement. 

PMID- 25760146
TI  - 3'-functionalized adamantyl cannabinoid receptor probes.
AB  - The aliphatic side chain plays a pivotal role in determining the cannabinergic
      potency of tricyclic classical cannabinoids, and we have previously shown that
      this chain could be substituted successfully by adamantyl or other polycyclic
      groups. In an effort to explore the pharmacophoric features of these
      conformationally fixed groups, we have synthesized a series of analogues in which
      the C3 position is substituted directly with an adamantyl group bearing
      functionality at one of the tertiary carbon atoms. These substituents included
      the electrophilic isothiocyanate and photoactivatable azido groups, both of which
      are capable of covalent attachment with the target protein. Our results show that
      substitution at the 3'-adamantyl position can lead to ligands with improved
      affinities and CB1/CB2 selectivities. Our work has also led to the development of
      two successful covalent probes with high affinities for both cannabinoid
      receptors, namely, the electrophilic isothiocyanate AM994 and the
      photoactivatable aliphatic azido AM993 analogues. 

PMID- 25760148
TI  - The Effect of Whole-body Vibration on Muscle Activity in Active and Inactive
      Subjects.
AB  - The purpose of this study was to compare lower limb muscle activity between
      physically active and inactive individuals during whole-body vibration exercises.
      Additionally, transmissibility of the vertical acceleration to the head was
      quantified. 30 active and 28 inactive participants volunteered to stand in a
      relaxed (20 degrees ) and a squat (60 degrees ) position on a side-alternating
      WBV platform that induced vibrations at 16 Hz and 4 mm amplitude. Surface
      electromyography (sEMG) was measured in selected lower limb muscles and was
      normalized to the corresponding sEMG recorded during a maximal voluntary
      contraction. The vertical acceleration on the head was evaluated and divided by
      the vertical platform acceleration to obtain transmissibility values. Control
      trials without vibration were also assessed. The outcomes of this study showed
      that (1) WBV significantly increased muscle activity in the active (absolute
      increase: +7%, P <0.05) and inactive participants (+8%, P <0.05), (2) with no
      differences in sEMG increases between the groups (P>0.05). However, (3),
      transmissibility to the head was greater in the active (0.080) than the inactive
      participants (0.065, P <0.05). In conclusion, inactive individuals show similar
      responses in sEMG due to WBV as their active counterparts, but are at lower risk
      for potential side-effects of vibration exposure. 

PMID- 25760149
TI  - Continuous Vocalization during Kendo Exercises Suppresses Expiration of CO2.
AB  - One distinctive trait of kendo, the Japanese martial art of fencing, is the
      execution of sustained, high-effort vocalizations during actions. The purpose of
      this study was to determine the effect of these vocalizations on respiratory
      functions. First, the intensity of 3 kendo exercises was quantified by measuring
      oxygen uptake (VO2) and comparing it with VO2max measured during treadmill tests
      of 8 university kendo athletes. Respiratory variables of these 8 athletes were
      then analyzed using a portable breath gas analyzer during the most intensive
      kendo exercise, kakari-keiko, with and without vocalization. Breathing frequency
      (fB) increased regardless of vocalization, but in trials with vocalization, fB
      and ventilation were significantly lower, and expiration time was significantly
      longer. Components of expired gases were also affected by vocalization. Although
      there was no significant difference in oxygen uptake, vocalization yielded a
      reduction in carbon dioxide output (VCO2) and an increase in fraction of end
      tidal carbon dioxide (FetCO2). We thus conclude that these vocalizations greatly
      affect expiration breathing patterns in kendo. Moreover, repetition of kakari
      keiko caused a reduction in VCO2 and an increase in FetCO2 and CO2 storage. We
      consider the possibility that the sustained high-effort vocalizations of kendo
      also increase cerebral blood flow. 

PMID- 25760150
TI  - Assessing the Effectiveness of Selected Biomarkers in the Acute and Cumulative
      Physiological Stress Response in Professional Rugby Union through Non-invasive
      Assessment.
AB  - Rugby union is a sport involving high force and frequency impacts making the
      likelihood of injury a significant risk. The aim of this study was to measure and
      report the individual and group acute and cumulative physiological stress
      response during 3 professional rugby games through non-invasive sampling. 24
      professional rugby players volunteered for the study. Urine and saliva samples
      were collected pre and post 3 matches. Myoglobin, salivary immunoglobulin A,
      cortisol, neopterin and total neopterin (neopterin+7,8-dihydroneopterin) were
      analysed by high performance liquid chromatography or enzyme linked immunosorbent
      assay. Significant increases in cortisol, myoglobin, neopterin and total
      neopterin when urine volume was corrected with specific gravity were observed
      (p<0.05). Significant decreases in salivary immunoglobulin A concentration were
      observed for games 1 and 2 while secretion rate decreased after games 2 and 3.
      Significant decreases were seen with the percent of 7,8-dihydroneopterin being
      converted to neopterin following games 2 and 3. The intensity of 3 professional
      rugby games was sufficient to elicit significant changes in the physiological
      markers selected for our study. Furthermore, results suggest the selected markers
      not only provide a means for analysing the stress encountered during a single
      game of rugby but also highlight the unique pattern of response for each
      individual player. 

PMID- 25760151
TI  - Autophagic Adaptations to Long-term Habitual Exercise in Cardiac Muscle.
AB  - Autophagy has been shown to be responsive to physical exercise. However, the
      effects of prolonged habitual exercise on autophagy in cardiac muscle remain
      unknown. The present study aimed to examine whether long-term habitual exercise
      alters the basal autophagic signalling in cardiac muscle. Female Sprague-Dawley
      rats aged 2 months were randomly assigned to control and exercise groups. Animals
      in exercise group were kept in cages with free access exercise wheels to perform
      habitual exercise for 5 months. Animals in the control group were placed in cages
      without exercise wheels. Ventricular muscle tissues were harvested for analysis
      after 5 months. Phosphorylation statuses of upstream autophagic regulatory
      proteins and protein expressions of downstream autophagic facts remained
      unchanged in the cardiac muscle of exercise animals when compared to control
      animals. Intriguingly, the protein abundance of microtubule-associated protein-1
      light chain -3 II (LC3-II), heat shock protein 72 (HSP72) and peroxisome
      proliferator-activated receptor-gamma coactivator (PGC-1alpha) were significantly
      increased in cardiac muscle of exercise rats relative to control rats. 5 months
      of habitual exercise causes the adaptive increase in LC3-II reserve without
      altering autophagic flux, which probably contributes to the elevation of cellular
      autophagic capacity and efficiency of cardiac muscle. 

PMID- 25760152
TI  - Match Running Performance and Success Across a Season in German Bundesliga Soccer
      Teams.
AB  - The aim of the study was to quantify the association between match running
      performance and success across a season in soccer teams competing within a
      European top league. We analyzed the match running performance data of all soccer
      teams from the German Bundesliga across the season 2012/13 (306 matches). The
      following match running performance data were used: total distance covered as
      well as number of running activities>18.0 km/h and > 22.7 km/h. Depending on the
      team's ball possession status, all match running performance data were also
      analyzed as those with and without ball possession. The success across the season
      was defined as the final competition points accumulated. The match running
      performance alone was not significantly correlated with the final points
      accumulated (best r=0.24; p=0.34). In contrast, positive-significant correlations
      were observed for the match running performance with ball possession (best
      r=0.77; p<0.01). However, of these latter correlations, only the total distance
      covered with ball possession was a significant predictor (p<0.01) and accounted
      for 60% of the variance (R(2)=0.60) in the final points accumulated. It is
      concluded that it is not the match running performance alone that is important
      for achieving success in German Bundesliga soccer teams, but rather its relation
      to technical/tactical skills with respect to ball possession. 

PMID- 25760153
TI  - Neuromuscular Responses to 14 Weeks of Traditional and Daily Undulating
      Resistance Training.
AB  - This study compared traditional (TP) and daily undulating (DUP) periodization on
      muscle strength, EMG-estimated neural drive and muscle architecture of the
      quadriceps femoris (QF). 10 non-athletic females (24.4+/-3.2 years) performed 14
      weeks of isometric training for the QF exercising 1 leg using TP and the
      contralateral leg using DUP. Intensities varied from 60% to 80% of MVC and the
      intensity zones and training volume were equated for each leg. Knee extension
      MVC, maximal voluntary QF-EMG activity and vastus lateralis (VL) muscle
      architecture were measured in both legs before, after 6 weeks and after 14 weeks
      of training using dynamometry, surface EMG and ultrasonography. Isometric MVC and
      maximal QF-EMG remained unaltered after 6 weeks of training, but were
      significantly (P<0.05) enhanced after 14 weeks in both legs (MVC: TP 24%, DUP
      23%; QF-EMG: TP 45%, DUP 46%). VL-architecture remained unchanged following 6
      weeks of training, but VL-muscle thickness (TP 17%, DUP 16%) and fascicle length
      (TP 16%, DUP 17%) displayed significant (P<0.05) enlargements after 14 weeks in
      both legs. Importantly, these temporal neuromuscular alterations displayed no
      significant differences between the training legs. Therefore, periodization may
      not act as a key trigger for neuromuscular adaptations. 

PMID- 25760154
TI  - Does Regular Post-exercise Cold Application Attenuate Trained Muscle Adaptation?
AB  - This study examined the effects of regular post-exercise cold application on
      muscular and vascular adaptations induced by moderate-intensity resistance
      training. 14 male subjects participated in resistance training: 5 sets of 8 wrist
      flexion exercises at workload of 70-80% of the single repetition maximum, 3 times
      a week for 6 weeks. 7 subjects immersed their experimental forearms in cold water
      (10+/-1 degrees C) for 20 min after wrist-flexion exercises (cooled group), and
      the other 7 served as control subjects (noncooled group). Measurements were taken
      before and after the training period; wrist-flexor thickness, brachial-artery
      diameter, maximal muscle strength, and local muscle endurance were measured in
      upper extremities. Wrist-flexor thicknesses of the experimental arms increased
      after training in both groups, but the extent of each increase was significantly
      less in the cooled group compared with the noncooled group. Maximal muscle
      strength and brachial-artery diameter did not increase in the cooled group, while
      they increased in the noncooled group. Local muscle endurance increased in both
      groups, but the increase in the cooled group tended to be lower compared to the
      noncooled group. Regular post-exercise cold application to muscles might
      attenuate muscular and vascular adaptations to resistance training. 

PMID- 25760155
TI  - Why open source?

PMID- 25760156
TI  - The effect of tobacco additives on smoking initiation and maintenance.

PMID- 25760157
TI  - So it is, if it seems...

PMID- 25760159
TI  - [Translation and cross-cultural adaptation of the World Health Organization staff
      questionnaire on dengue warning signs for use in Brazil].
AB  - Early recognition of warning signs and treatment of severe dengue cases is the
      main strategy for reducing case-fatality, especially in children, who usually
      present few symptoms and can progress rapidly to dengue shock syndrome. The
      objective of this study was to elaborate the Brazilian version of the World
      Health Organization (WHO) staff questionnaire on the use and value of dengue
      warning signs, through translation and back-translation of the WHO questionnaire,
      followed by an expert panel consensus, pretest (n = 13), and pilot study (n = 20)
      of the preliminary version. Comparison of the original questionnaire in English
      and the back-translation showed that 8 of the 49 items had been extensively or
      completely altered, and three were rephrased. The expert panel added the warning
      signs listed by the Brazilian Ministry of Health. In the final version of the
      questionnaire, the item "ranking of warning signs" was rephrased and the answer
      option "do not know" was excluded. The Brazilian version of the WHO staff
      questionnaire allows assessing health professionals' experience and perceptions
      regarding the use of warning signs included in the recent dengue guidelines. 

PMID- 25760158
TI  - The impact of migration on body weight: a review.
AB  - Immigrants may be more vulnerable to obesity as a result of the immigration
      process. The aim of this article is to summarize current knowledge about the
      impact of immigration on body mass index (BMI). A systematic review was performed
      in accordance with PRISMA guidelines through a database search of scientific
      articles (last updated in August 2014). Thirty-nine articles were included and
      assessed. Results varied according to ethnic background, country of origin and
      host country. A consistent positive association between BMI and time since
      immigration was found among Hispanic, European and African immigrants. Less than
      half of the studies observed a positive association among Asian immigrants. The
      quality of the majority of the studies assessed was poor, reflecting a need to
      improve methodology and concept definition. Immigration appears to have a
      deteriorative effect on BMI. Underlying causes may include changes in nutrition
      and physical activity, psychological and social factors, and genetic
      susceptibility and these aspects should be included as moderator variables in
      future studies. 

PMID- 25760160
TI  - Going open source: some lessons learned from the development of OpenRecLink.
AB  - Record linkage is the process of identifying and merging records across different
      databases belonging to the same entity. The health sector is one of the
      pioneering areas of record linkage techniques applications. In 1998 we began the
      development of a software package, called RecLink that implemented probabilistic
      record linkage techniques. In this article we report the development of a new,
      open-source version of that program, now named OpenRecLink. The aim of this
      article is to present the main characteristics of the new version and some of the
      lessons learned during its development. The new version is a total rewrite of the
      program, based on three goals: (1) to migrate to a free and open source software
      (FOSS) platform; (2) to implement a multiplatform version; (3) to implement the
      support for internationalization. We describe the tools that we adopted, the
      process of development and some of the problems encountered.

PMID- 25760161
TI  - Air pollution and children's health: sickle cell disease.
AB  - The hallmarks of sickle cell disease are anemia and vasculopathy. The aim of this
      study was to assess the association between air pollution and children's
      emergency room visits of sickle cell patients. We adopted a case-crossover
      design. Daily counts of children's and adolescents' sickle cell disease emergency
      room visits from the pediatric emergency unit in Sao Paulo, Brazil, were
      evaluated from September 1999 to December 2004, matching by temperature, humidity
      and controlling for day of the week. Interquartile range increases of the four
      day moving averages of PM10, NO2, SO2, CO, and O3 were associated with increases
      of 18.9% (95%CI: 11.2-26.5), 19% (95%CI: 8.3-29.6), 14.4% (95%CI: 6.5-22.4),
      16,5% (95%CI: 8.9-24.0), and 9.8% (95%CI: 1.1-18.6) in total sickle cell
      emergency room visits, respectively. When the analyses were stratified by pain,
      PM10 was found to be 40.3% higher than in sickle cell patients without pain
      symptoms. Exposure to air pollution can affect the cardiovascular health of
      children and may promote a significant health burden in a sensitive group. 

PMID- 25760162
TI  - Impact of 10-valent pneumococcal conjugate vaccine on pneumococcal meningitis in
      children up to two years of age in Brazil.
AB  - The objective of this study was to analyze the impact of vaccination against
      Streptococcus pneumoniae on the morbidity and mortality from pneumococcal
      meningitis in children <= 2 years in Brazil, from 2007 to 2012. This is a
      descriptive study and ecological analysis using data from the Information System
      on Notifiable Diseases. Pre-vaccination (2007-2009) and post-vaccination (2011
      2012) periods were defined to compare incidence rates and mortality. A total of
      1,311 cases and 430 deaths were reported during the study period. Incidence
      decreased from 3.70/100,000 in 2007 to 1.84/100,000 in 2012, and mortality
      decreased from 1.30/100,000 to 0.40/100,000, or 50% and 69% respectively, with
      the greatest impact in the 6-11 month age group. This decrease in Pneumococcal
      meningitis morbidity and mortality rates two years after introduction of the 10
      valent pneumococcal conjugate vaccine suggests its effectiveness. 

PMID- 25760163
TI  - [Privatization of health care management through Social Organizations in the city
      of Sao Paulo, Brazil: description and analysis of regulation].
AB  - The article describes and discusses privatization of the municipal health system
      in Sao Paulo, Brazil, from an administrative and political perspective. The
      methodology consisted of a literature review and analysis of legislation and
      public documents. The study showed that although legislation governing the so
      called "Social Organizations" (OS) in Brazil dates to the year 2006, half of the
      administrative privatization is still regulated by a previous provisional
      instrument in the form of an "agreement" ("convenio" in Portuguese). In 2011, 61%
      of services were administered by private organizations, which received 44% of the
      health budget in 2012. The twenty participating organizations include five of the
      ten largest health care companies in Brazil. Inspection agencies have detected
      flaws in the management contracts, but the "agreements" (convenios) are subject
      to less rigorous control and have proven invisible to inspection. Finally, the
      legal framework is unstable. The study uses the experience in Sao Paulo as the
      basis for discussing the political versus technical nature of private management
      in the Brazilian Unified National Health System (SUS). 

PMID- 25760164
TI  - Empirically derived dietary patterns: interpretability and construct validity
      according to different factor rotation methods.
AB  - This study aimed to investigate the effects of factor rotation methods on
      interpretability and construct validity of dietary patterns derived in a
      representative sample of 1,102 Brazilian adults. Dietary patterns were derived
      from exploratory factor analysis. Orthogonal (varimax) and oblique rotations
      (promax, direct oblimin) were applied. Confirmatory factor analysis assessed
      construct validity of the dietary patterns derived according to two factor
      loading cut-offs (>= |0.20| and >= |0.25|). Goodness-of-fit indexes assessed the
      model fit. Differences in composition and in interpretability of the first
      pattern were observed between varimax and promax/oblimin at cut-off >= |0.20|. At
      cut-off >= |0.25|, these differences were no longer observed. None of the
      patterns derived at cut-off >= |0.20| showed acceptable model fit. At cut-off >=
      |0.25|, the promax rotation produced the best model fit. The effects of factor
      rotation on dietary patterns differed according to the factor loading cut-off
      used in exploratory factor analysis. 

PMID- 25760165
TI  - Sexual satisfaction in couples in the male and female climacteric stage.
AB  - The objective was to describe the sexual life satisfaction of couples in the
      climacteric stage and determine whether there are differences between the
      perception of satisfaction and the sex life of each partner. We studied 142
      couples obtained by stratified sampling of family health centers, Concepcion,
      Chile. 66% of women and 84% of men reported being very or somewhat satisfied with
      their sex lives. Slight concordance was found between the responses of the
      partners in relation to satisfaction with their sexual life. Moreover, a slight
      degree of agreement was found between the sexual life satisfaction reported by
      women and their partners' perceptions of the women's sexual life satisfaction.
      Additionally, a slight degree of agreement was reported between the sexual life
      satisfaction reported by men and their partners' perceptions of the men's sexual
      life satisfaction. This study provides new information about Chilean couples in
      the climacteric stage in relation to self-reported sexual satisfaction and
      perceived satisfaction in couples. 

PMID- 25760166
TI  - Health care seeking behavior and patient delay in tuberculosis diagnosis.
AB  - Delays in diagnosis of TB cases are major impeding factors in the control of TB.
      The objectives of this study were to describe the health care seeking behavior of
      TB patients, assessing patient delay and the number of health care facilities
      visited before the start of TB treatment. A cross-sectional study was carried out
      with adult patients with pulmonary TB presenting to two TB facilities to start
      treatment. We found a median patient delay of 20 days. The factors associated
      negatively with patient delay in multivariate analysis were weight loss, and have
      sought treatment because of the first symptom. We also demonstrated that 44.8% of
      patients incorrectly reported the mode of transmission of TB. In addition, the
      local of first attendance was an emergency room of public hospitals in 37.3% of
      patients. We demonstrated that the median patient delay in TB diagnosis in two TB
      services in a region with a high prevalence of TB was 20 days, and the protective
      factors associated with this delay in multivariate analysis were weight loss, and
      have sought treatment because of the first symptom. 

PMID- 25760167
TI  - Epidemiology of high blood pressure among the Kaingang people on the Xapeco
      Indigenous Land in Santa Catarina State, Brazil, 2013.
AB  - This cross-sectional study describes the prevalence of high blood pressure (HBP;
      measured at one setting, and suggestive of a clinical diagnosis of arterial
      hypertension) and mean systolic blood pressure (SBP) and diastolic blood pressure
      (DBP) and their associations with socio-demographic and anthropometric variables
      among 355 Kaingang adults (>= 20 years) on the Xapeco Indigenous Land in Brazil.
      Weight, height, waist circumference (WC), SBP, and DBP were measured and socio
      demographic data were collected. Prevalence of HBP was 53.2% (95%CI: 45.3; 61.1)
      in men and 40.7% (95%CI: 33.8; 47.6) in women. In women, age and WC were directly
      associated with HBP; age was associated with SBP and schooling with DBP. In men,
      HBP was statistically associated with high body mass index (BMI) and tile floor
      in the home (as a socioeconomic proxy); BMI and WC were associated with SBP; BMI
      and WC were associated with DBP. The study highlights the need for measures to
      control risk factors for HBP, especially due to its relevance for cardiovascular
      diseases and their consequences. 

PMID- 25760168
TI  - [Rape-related pregnancy in Brazil: the experience of women seeking legal
      abortion].
AB  - In Brazil, abortion is permitted by law in cases of rape-related pregnancy. This
      study reports on various aspects in the experience of women that have been
      sexually assaulted: diagnosis of the pregnancy, seeking legal abortion, and
      hospitalization in a university hospital. This was a qualitative study that
      interviewed ten women 18 to 38 years of age, with at least eight years of
      schooling, one to five years after legal abortion. The women had been previously
      unaware of their right to a legal abortion, were ashamed about the sexual
      assault, kept it secret, and had not sought immediate care. The diagnosis of
      pregnancy provoked anxiety and the wish to undergo an abortion. Women treated
      through private health plans received either insufficient orientation or none at
      all. Respectful treatment by the healthcare staff proved relevant for the women
      to cope with the abortion. The study highlights the need to publicize the right
      to abortion in cases of rape-related pregnancy and the healthcare services that
      perform legal abortion, in addition to training healthcare and law enforcement
      teams to handle such cases. 

PMID- 25760169
TI  - [Public demonstrations for health as a fundamental human right in Colombia: 1994
      2010].
AB  - This study reconstructs the health struggle in Colombia during implementation of
      the health reform from 1994 to 2010, based on an analysis of primary and
      secondary sources. The study focus is political struggle, a theory of collective
      action based on a relational perspective between collective actors and the
      political structure to comprehend historical transformations. Three episodes in
      the struggle are reconstructed, revealing a causal link between protests and
      structural reforms in social and health policy. The struggles by subordinate
      actors highlighted the dispossession of labor rights, crisis in public hospitals,
      and access barriers to services as adverse effects of the reform, even while
      government favored private capital interests. The protests continued despite anti
      union violence and government crackdown, while new actors and a national health
      movement reshaped the public sphere, building an identity around the struggle for
      the fundamental right to health. 

PMID- 25760170
TI  - [Quality of life and AIDS from the perspective of persons living with HIV: a
      preliminary contribution by the structural approach to social representations].
AB  - This descriptive qualitative study had the following objectives: identify the
      content and structure of social representations of quality of life and AIDS for
      persons living with the disease and analyze the structural relations between such
      representations. The sample included 103 persons with HIV in a municipality
      (county) in northern Rio de Janeiro State, Brazil. The methodology used free and
      hierarchical recall of words for the inductive terms "AIDS" and "quality of life
      for persons with AIDS", with analysis by the EVOC software. The probable core
      representation of AIDS was identified as: prejudice, treatment, family, and
      medications, with the same components identified for quality of life, plus
      healthy diet and work. We thus elaborated the hypothesis of joint, coordinated
      representational interaction, fitting the representations together, with
      implications for the symbolic grasp and quality of life for persons living with
      HIV. The findings provide backing for collective and individual health approaches
      to improve quality of life in this group. 

PMID- 25760171
TI  - [Assessing complementary feeding practices in the first two years of life: a
      proposal for indicators and a monitoring tool].
AB  - The aim of this article is to propose indicators and a tool for monitoring
      complementary feeding in under-two children in Brazil, describing its
      formulation. The study constructed a theoretical model of attributes, components,
      and markers of complementary feeding that serves as the basis for systematizing
      the feeding recommendations related to key concepts in the model. The
      recommendations were transformed into indicators. A questionnaire was
      constructed, based on the indicators' variables. Two workshops were held with
      specialists in complementary feeding to discuss the indicators and the
      instrument, in addition to four pretests with the target population. The study
      presents 18 indicators related to the timing, nutritional adequacy, and safety of
      complementary feeding, as well as a questionnaire that allows the construction of
      the proposed indicators. The model can be applied in surveys with face-to-face or
      telephone interviews or in activities in health services to monitor food
      consumption. Further research is necessary to validate the questionnaire. 

PMID- 25760172
TI  - [Evaluation of knowledge on blood pressure levels and chronicity of hypertension
      among users of a public pharmacy in Southern Brazil].
AB  - The aim of this study was to evaluate patients' knowledge on hypertension and
      associated factors through a cross-sectional study of adults using
      antihypertensive medication dispensed by the Sao Francisco de Paula Public
      Pharmacy in Rio Grande do Sul State, Brazil. The study evaluated knowledge on the
      normal limits for systolic and diastolic blood pressure and chronicity of
      hypertension. Multinomial regression was used to measure knowledge
      (satisfactory/moderate/unsatisfactory); satisfactory was defined as correct
      knowledge on two or more items. Of the 635 users with hypertension, 27.7% showed
      satisfactory knowledge, while 47.2% were only aware of the chronic nature of
      hypertension. After adjustment, female gender, more education, not living alone,
      healthy lifestyle, and greater time since diagnosis were associated with
      satisfactory knowledge on hypertension. Considering the importance of patient
      autonomy in monitoring blood pressure and continuous treatment to control
      hypertension, the study showed a low prevalence of satisfactory knowledge. 

PMID- 25760173
TI  - [Mortality from meningococcal disease in the city of Sao Paulo, Brazil:
      characteristics and predictors].
AB  - This study aimed to describe the magnitude, mortality, and case-fatality rate
      from meningococcal disease and to investigate predictors of death from this cause
      in the city of Sao Paulo, Brazil, from 1986 to 2004, using unconditional multiple
      logistic regression. We analyzed 10,087 cases of meningococcal disease in the
      city. Mean annual mortality was 1.0/100,000 inhabitants, ranging from 0.2 to 1.8.
      Case-fatality was 20.5%, with major differences according to age, serogroup, and
      type of hospital. Predictors of death from meningococcal disease were age,
      especially the age brackets from one to two years and 40 years and older, and
      serogroup W. The results can contribute to the elaboration of public policies
      with a focus on the organization of hospital care and protocols to promote
      greater treatment effectiveness and application of vaccination strategies that
      decrease the incidence in groups at greatest risk of death from meningococcal
      disease. 

PMID- 25760174
TI  - [Disparities in mental health associated with sexual orientation among Mexican
      adolescents].
AB  - The aim of this study was to document disparities in mental health related to
      discrimination based on sexual orientation in Mexican adolescents. A
      representative national sample of secondary school students was analyzed.
      Criteria for homosexual orientation were having had a same-sex boyfriend or
      girlfriend and having had same-sex sexual relations. The events were: depression,
      low self-esteem, suicidal ideation, attempted suicide, smoking, alcohol abuse,
      and drug use. Teenagers with same-sex relationships or sexual relations had an
      increased risk of depressive symptoms, suicidal ideation, attempted suicide, and
      alcohol abuse. These differences were particularly related to having experienced
      violence in the family and in school. Despite institutional and legal progress in
      acknowledging the rights of the lesbian, bisexual, and gay population, health
      inequities persist due to discrimination based on sexual orientation. 

PMID- 25760175
TI  - [Training health workers to deal with sexual abuse of children and adolescents in
      Fortaleza, Ceara State, Brazil].
AB  - This study aimed to identify initiatives for training staff in the municipal
      healthcare system in Fortaleza, Ceara State, Brazil, to deal with cases of sexual
      abuse of children and adolescents. The reference for this exploratory study was
      the training program provided by the municipal government in 2010-2012 for
      administrators and health professionals in the public healthcare system in
      Fortaleza. At the time, the issue of sexual abuse was low in the system's
      training programs, despite recognition of its importance. Federal and State
      programs have provided input for such training programs in the various municipal
      health departments. The main strategy was to invest in training for health
      workers in primary care. Social workers were found to have insufficient training,
      aggravated by temporary work contracts and high staff turnover. The study
      suggests the need for training to deal with violence, particularly sexual abuse. 

PMID- 25760176
TI  - A pilot study of colon lymph node counts on Faxitron (radiographs) compared with
      pathology reports.

PMID- 25760177
TI  - An approach to the diagnosis and treatment of gastrointestinal bleeding secondary
      to jejunal diverticulosis.

PMID- 25760178
TI  - Early use of split-thickness skin graft allows separation of the wound into
      different compartments facilitating the collection of enteroatmospheric fistulae
      output.

PMID- 25760179
TI  - Colonic duplication.

PMID- 25760180
TI  - Cholangiocarcinoma arising from intraductal papillary mucinous neoplasm of the
      bile duct.

PMID- 25760181
TI  - Extramedullary plasmacytoma of the small intestine.

PMID- 25760182
TI  - A rare tumor: mucinous cystadenocarcinoma of the breast.

PMID- 25760183
TI  - Use of porcine dermal allograft to prevent pulmonary herniation in a patient with
      multiple displaced rib fractures requiring surgical fixation.

PMID- 25760184
TI  - Ruptured duodenal diverticulum after blunt abdominal trauma.

PMID- 25760185
TI  - Wunderlich syndrome: the role of the general surgeon.

PMID- 25760186
TI  - Surgical intervention for a foreign body trapped in the stomach.

PMID- 25760187
TI  - Pathology encountered on short-term surgical mission trips to the Dominican
      Republic.

PMID- 25760188
TI  - Beauty parlor stroke syndrome: a rare entity in a trauma patient.

PMID- 25760189
TI  - Incarcerated massive sliding hernia treated with bladder resection and mesh
      repair.

PMID- 25760190
TI  - Novel method of anchoring the pleurodesis talc-spraying catheter to the
      thoracoscopic camera.

PMID- 25760191
TI  - All-terrain vehicle accident trends at a Tennessee trauma center in 2014.

PMID- 25760192
TI  - Ruptured jejunal artery aneurysm.

PMID- 25760193
TI  - Management of a complex degloving posterior thigh injury with a dynamic wound
      closure device.

PMID- 25760194
TI  - Treatment of benign rectal strictures with proctoplasty.

PMID- 25760195
TI  - Management of severe perianal herpes.

PMID- 25760196
TI  - Rural pediatric surgery.
AB  - Published outcome studies support regionalization of pediatric surgery, in which
      all children suspected of having surgical disease are transferred to a specialty
      center. Transfer to specialty centers, however, is an expensive approach to
      quality, both in direct costs of hospitalization and the expense incurred by
      families. A related question is the role of well-trained rural surgeons in an
      adequately resourced facility in the surgical care of infants and children. Local
      community facilities provide measurably equivalent results for straightforward
      emergencies in older children such as appendicitis. With education, training, and
      support such as telemedicine consultation, rural surgeons and hospitals may be
      able to care for many more children such as single-system trauma and other cases
      for which they have training such as pyloric stenosis. They can recognize
      surgical disease at earlier stages and initiate appropriate treatment before
      transfer so that patients are in better shape for surgery when they arrive for
      definitive care. Rural and community facilities would be linked in a pediatric
      surgery system that covers the spectrum of pediatric surgical conditions for a
      geographical region. 

PMID- 25760197
TI  - Surgeons and their tools: a history of surgical instruments and their innovators.
      Part V: pass me the hemostat/clamp.
AB  - This is the last of five manuscripts reviewing the historical origins of some of
      the more commonly used surgical instruments and takes "time out" to remind
      current surgeons about the surgical pioneers on whose shoulders they now stand
      and whose inventions they now use. 

PMID- 25760198
TI  - The effect of body mass index on posttraumatic transfusion after pelvic trauma.
AB  - The impact of body mass index (BMI) on posttraumatic blood transfusion after
      pelvic trauma is not well known. We conducted a retrospective review of trauma
      registry data over a 5-year period. Patients were stratified by BMI as normal:
      less than 25 kg/m(2), overweight: 25 to 29.9 kg/m(2), obese: 30 to 39.9 kg/m(2),
      and morbidly obese: 40 kg/m(2) or greater. Fractures were identified as "likely
      to receive transfusion" based on literature. Multivariable logistic regression
      modeling evaluated the relationship between BMI and initial posttraumatic
      transfusion. A second regression model was created to test the effect of BMI
      after adjusting for fractures "less likely to receive transfusion." Sixty-six of
      244 patients (27.3%) received transfusion (mean: 1.1 +/- 2.3 units). Morbid
      obesity was associated with transfusion (less than 55.6 vs 24.8%; P < 0.05) and
      units of total blood transfused (2.2 +/- 2.9 vs 1.0 +/- 2.2 mL; P < 0.05). The
      average age of patients who received a blood transfusion was significantly older
      compared with patients who did not receive a transfusion (45.4 +/- 18.8 vs 36.1
      +/- 16.1 years; P < 0.05). After adjusting for potential confounders, morbid
      obesity was a significant risk factor for transfusion (odds ratio [OR], 4.1; 95%
      confidence interval [CI], 1.4 to 12.0). Adjusting by age and fracture patterns
      "less likely to receive transfusion," morbid obesity remained a risk factor for
      transfusion (OR, 4.5; 95% CI, 1.5 to 12.9). Morbid obesity represented a
      significant risk factor for posttraumatic transfusion in isolated pelvic trauma,
      even for fracture patterns "less likely to receive transfusion." 

PMID- 25760199
TI  - Outcomes of pediatric patients with abdominal sepsis requiring surgery and
      extracorporeal membrane oxygenation using the Extracorporeal Life Support
      Organization database.
AB  - No study describes the use of extracorporeal membrane oxygenation (ECMO) in
      pediatric patients with abdominal sepsis (AS) requiring surgery. A description of
      outcomes in this patient population would assist clinical decision-making and
      provide a context for discussions with patients and families. The Extracorporeal
      Life Support Organization database was queried for pediatric patients (30 days to
      18 years) with AS requiring surgery. Forty-five of 61 patients survived (73.8%).
      Reported bleeding complications (57.1 vs 48.8%), the number of pre-ECMO
      ventilator hours (208.1 vs 178.9), and the timing of surgery before (50 vs 66.7%)
      and on-ECMO (50 vs 26.7%) were similar in survivors and nonsurvivors. Decreased
      pre-ECMO mean pH (7.1 vs 7.3) was associated with increased mortality (odds
      ratio, 1.49; 95% confidence interval, 1.04 to 2.14). ECMO use for pediatric
      patients with AS requiring surgery is associated with increased mortality and an
      increased rate of bleeding complications compared with all pediatric patients
      receiving ECMO support. Acidemia predicts mortality and provides a potential
      target of examination for future studies. 

PMID- 25760200
TI  - Effectiveness of a clinical pathway for inpatients undergoing ileal/ileocecal
      resection for chronic radiation enteritis with intestinal obstruction.
AB  - Surgery is associated with elevated morbidity and mortality in chronic radiation
      enteritis (CRE). The objective of this study was to evaluate the effect of a fast
      track clinical pathway (CP) on postoperative outcomes in patients undergoing
      ileal/ileocecal resection for CRE with intestinal obstruction. There were 85
      patients with CRE (January 2011 to March 2013) with intestinal obstruction
      admitted to our department for ileal/ileocecal resection. The patients were
      divided into a prepathway group and a pathway group. The clinical outcomes were
      then assessed and compared. The postoperative lengths of hospital stay were 8.52
      days for the pathway group and 11.32 days for the prepathway group (P = 0.02).
      The pathway group had a lower stoma rate (21.6 vs 56%, P = 0.033) and fewer
      postoperative moderate to severe complications (8.1 vs 25%, P = 0.043) compared
      with the prepathway group. Implementation of the CP may reduce stoma rate,
      postoperative moderate to severe complications, and postoperative length of
      hospital stay for patients undergoing ileal/ileocecal resection for the treatment
      of CRE with intestinal obstruction. 

PMID- 25760201
TI  - Race influences stage-specific survival in gastric cancer.
AB  - Gastric adenocarcinoma studies show improved survival for Asians but have not
      reported stage-specific overall survival (OS) or disease-specific survival (DSS)
      by race. The Surveillance, Epidemiology and End Results database was queried for
      cases of gastric adenocarcinoma between 1998 and 2008. We evaluated OS and DSS by
      race and stage. Number of assessed lymph nodes was compared among surgical
      patients. Of 49,058 patients with complete staging data, 35,300 were white, 7709
      were Asian, and 6049 were black. Asians had significantly better OS for all
      stages (P < 0.001) and significantly better DSS for Stages I (P < 0.0001) and II
      (P = 0.0006). As compared with blacks, whites had significantly better DSS for
      Stages I (P < 0.0001), II (P = 0.0055), III (P = 0.0165), and IV (P < 0.0001).
      Among the 28,133 (57%) surgical patients, average number of evaluated lymph nodes
      was highest for Asians (P < 0.0001). Among surgical patients with 15 or more
      nodes evaluated, DSS was worse in blacks with Stage I disease (P < 0.05). Blacks
      with gastric adenocarcinoma have a worse DSS, which disappears when surgical
      treatment includes adequate lymphadenectomy. Race-associated survival differences
      for gastric adenocarcinoma might simply reflect variations in surgical staging
      techniques and socioeconomic factors. 

PMID- 25760202
TI  - Initial experience with thoracoscopic esophageal atresia and tracheoesophageal
      fistula repair: lessons learned and technical considerations to achieve success.
AB  - The minimally invasive surgical (MIS) repair of esophageal
      atresia/tracheoesophageal fistula (EA/TEF) is challenging and requires advanced
      endoscopic skills. The purpose of this study was to provide insight in
      successfully introducing the MIS repair based on the initial cases performed by a
      single pediatric surgeon and review of the experience of others. A retrospective
      review of all MIS TEF repairs performed by a single surgeon was conducted. Data
      gathered included patient demographics, technical details of repair including
      operative time, short- and long-term postoperative morbidity, length of stay, and
      follow-up. Eight cases (seven Type C, one Type D) were selected for MIS repair
      based on the judgment of the surgeon with consideration of adequate patient size,
      stability, type of associated anomalies, and expected length of esophageal gap.
      Operative time was an average of 207 minutes and there was one conversion to open
      for successful repair. There were no leaks and only one patient required a single
      anastomotic dilation at 19 months of age. There were two postoperative
      pneumothoraces of which one required bronchoscopic laser fistula ablation. Length
      of stay was an average of 16 days and length of follow-up is a median of 219
      days. MIS repair of EA/TEF can be done successfully but requires careful patient
      selection, advanced MIS skills and meticulous attention to operative technique. 

PMID- 25760203
TI  - Transanal minimally invasive surgery (TAMIS): new treatment for early rectal
      cancer and large rectal polyps-experience of an Italian center.
AB  - Transanal endoscopic microsurgery (TEM) is a minimally invasive technique for
      excision of rectal tumors that avoids conventional pelvic resectional surgery
      along with its risks and side effects. Although appealing, the associated cost
      and complex learning curve limit TEM use by colorectal surgeons. Transanal
      minimally invasive surgery (TAMIS) has emerged as an alternative to TEM. This
      platform uses ordinary laparoscopic instruments to achieve high-quality local
      excision. The aim of the study is to assess reliability of the technique. From
      July 2012 to August 2013, 15 consecutive patients with rectal pathology underwent
      TAMIS. After a single-incision laparoscopic surgery port was introduced into the
      anal canal, a pneumorectum was established with a laparoscopic device followed by
      transanal excision with conventional laparoscopic instruments, including
      graspers, electrocautery, and needle drivers. Patient demographics, operative
      data, and pathologic data were recorded. Of the 15 patients, 10 had rectal
      cancers (six T1 lesions and four T2 after preoperative chemoradiotherapy). The
      remainder of patients had a local excision for voluminous benign rectal adenomas.
      The median length of the lesions from the anal verge was 7 cm (range, 4 to 20
      cm). The median operating time was 86 minutes (range, 33 to 160 minutes). There
      was no surgical morbidity or mortality. The median postoperative hospital stay
      was two days (range, 1 to 4 days). TAMIS seems to be a feasible and safe
      treatment option for early rectal cancer. We believe that this new technique is
      easy to perform, cost-effective, and less traumatic to the anal sphincter
      compared with traditional TEM. 

PMID- 25760204
TI  - The incidence of over-the-counter medication use in patients with midgut
      neuroendocrine tumors.
AB  - Recent increases in the use of over-the-counter (OTC) medicines and the
      underreporting of the use of these medications to physicians have sparked
      interest in the number and types of "supportive" therapies used by patients with
      neuroendocrine tumors (NETS). Patients with NETS are of special interest as a
      result of the potential interactions/interferences between tumor-associated
      peptide and amine production and OTC supplements. A prospective analysis of
      patients with primary small bowel NETS between 1998 and 2012 was conducted to
      define and catalog each patient's prescription and OTC medication use at each
      clinic visit. The most recently recorded patient medications were used for this
      analysis. Three hundred sixty-two patients with small bowel primary NETS were
      studied. One hundred eighty-seven patients (51.6%) were taking nutritional
      supplements. Of these taking supplements, the per cent of patients taking one,
      two, three, or more than three supplements was 28.3, 24.1, 22.5, and 25.1 per
      cent, respectively. Females (n = 109) were more likely to take supplements in
      comparison to males (n = 78; P = 0.037). Fifty one patients (14.1%) took proton
      pump inhibitors and 31 patients (8.6%) took loperamide. OTC supplements were used
      by 50 per cent of patients with primary small bowel NETS in this study. Over one
      third of our patients reported using three or more OTC medicines daily. These
      medicines have the potential to interact with the metabolism of prescribed
      medicines, modify ability to clot during surgery, exacerbate NET symptoms, and
      alter NET markers. Given the prevalence of OTC medications and their potential
      actions, it is important to carefully catalog their use. 

PMID- 25760205
TI  - Appendectomy and pregnancy: gestational age does not affect the position of the
      incision.
AB  - The position of the base of the appendix during advancing gestational age is
      based on inadequate data. Therefore, the proper location for an appendectomy
      incision during pregnancy is highly unclear. This study investigated the location
      of the appendix during pregnancy to determine the optimal location for an
      incision in pregnant patients with appendicitis relative to McBurney's point.
      Magnetic resonance images (MRIs) were reviewed independently by two fellowship
      trained abdominal MRI radiologists blinded to the imaging report. The distance of
      the appendix from anatomic landmarks was measured in a total of 114 pregnant
      women with an abdominal or pelvic MRI who were admitted between 2001 and 2011 at
      a Level I trauma center. Patients with a history of appendectomy were excluded.
      The distance from the base of the appendix to McBurney's point changed over the
      course of the gestation by only 1.2 cm and which did not amount to a clinically
      or statistically significant change in position. Our data provide evidence that
      there is minimal upward or lateral displacement of the appendix during pregnancy,
      and therefore its distance from the McBurney's point remains essentially
      unchanged. These findings justify the use of the McBurney's incision for
      appendectomy during pregnancy regardless of the trimester. 

PMID- 25760206
TI  - Disease recurrence patterns and analysis of clinicopathological prognostic
      factors for recurrence after resection for distal bile duct cancer.
AB  - Surgical resection is the treatment of choice for bile duct cancers. The aim of
      this study was to investigate disease recurrence patterns and prognostic factors
      for recurrence of distal bile duct cancers after surgical resection. A
      retrospective study was performed on 122 patients with distal bile duct cancers
      who underwent R0 or R1 surgical resection at Korea University Guro Hospital from
      1991 to 2010. Sites of initial disease recurrence were classified as locoregional
      or distant. Univariate and multivariate analyses were performed to investigate
      the factors affecting recurrence. Of the 122 patients, 80 patients developed
      recurrence. The disease-free survival rate was 63.1 per cent at one year and 36.4
      per cent at three years. The patterns of recurrence at diagnosis were
      locoregional in 25 patients, locoregional and distant metastasis in 14 patients,
      and distant metastasis in 41 patients. Multivariate analyses revealed that
      recurrence pattern, lymph node metastasis, and differentiation are independent
      prognostic factors affecting disease-free survival. R status (marginal
      significance) and tumor differentiation were independent prognostic factors
      associated with locoregional recurrence. Differentiation and lymph node
      metastasis were independent prognostic factors associated with distant
      metastasis. The prognosis after recurrence was poor with a 1-year survival rate
      after recurrence of 26.1 per cent. Adjuvant chemo- or radiation therapy,
      delivered in patients mainly with R1 resection or with presence of lymph node
      metastasis, did not demonstrate the survival benefit. Significant factors for
      recurrence were tumor differentiation and lymph node metastasis. Therefore, close
      follow-up and adjuvant therapy will be necessary in patients with lymph node
      metastasis or poorly differentiated tumor. 

PMID- 25760207
TI  - Pathologic findings suggest long-term abnormality after conservative management
      of complex acute appendicitis.
AB  - Perforated or phlegmonous appendicitis is often treated with antibiotics and
      drainage as needed. The rationale, risk of recurrence, timing, or even the
      necessity of subsequent elective interval appendectomy (IA) is debated. We
      retrospectively reviewed all appendectomies performed at Beth Israel Deaconess
      Medical Center between 1997 and 2011. We determined if the appendix was removed
      emergently or as IA. Demographic characteristics, hospital length of stay,
      computed tomography (CT) results, and operation type (open or laparoscopic) were
      determined. In IA specimens, narrative pathology reports were assessed for
      evidence of anatomic, acute, or chronic abnormality. A total of 3562 patients had
      their appendix removed during this time period. Thirty-four patients were
      identified as having IA. Of these, only three (8.8%) had a pathologically normal
      appendix. All three patients were female and all had initially abnormal CT scans.
      Eight specimens (23.5%) had evidence of chronic and 10 (29.4%) had evidence of
      acute appendicitis. An additional 10 (29.4%) specimens contained a combination of
      acute and chronic inflammation. Mean time to operation in the IA group was 57.1
      days (range, nine to 234 days) after index diagnosis by CT scan. Given the high
      percentage of IA specimens with acute or chronic appendicitis and the extremely
      high proportion (91%) of patients with pathologically abnormal specimens, it
      appears that IA may be justified in most cases. 

PMID- 25760208
TI  - The effect of watchful waiting on the management and treatment of inguinal
      hernias in a community setting.
AB  - A landmark study by Fitzgibbons et al. reported the safety of watchful waiting in
      men with minimally symptomatic inguinal hernias. The extent to which this study
      has changed practice patterns is unknown. The purpose of our study was to survey
      physicians caring for patients with hernia in our community to determine if the
      Fitzgibbons report impacted their medical practices. We sent an electronic survey
      containing questions regarding physician background and familiarity with the 2006
      New England Journal of Medicine report on watchful waiting to physicians in our
      community. The online survey was accessed by 77 physicians; 74 completed the
      survey. Of 74 participants, surgeons accounted for 15 per cent, family/internal
      medicine 42 per cent, and 13 other specialties 43 per cent. Nonsurgeons were less
      familiar with the Fitzgibbons report. All surgeons had heard of the study, and 73
      per cent had read it compared with 3 per cent of nonsurgeons. In nonsurgeon
      physicians, 38 per cent preferred letting patients with inguinal hernia decide
      treatment after counseling, 30 per cent sent all patients to a surgeon, and 25
      per cent sent only symptomatic patients to a surgeon. Surgeons let patients
      decide after counseling in 73 per cent and chose watchful waiting for
      asymptomatic patients/offered surgery to symptomatic patients in 27 per cent.
      Based on our survey, Fitzgibbons' watchful waiting report does not appear to have
      significantly impacted practice and referral patterns in our community, although
      the watchful waiting strategy outlined in the study is practiced. Our study
      illustrates the challenge of translating research outcomes into clinical
      practice. Further research on ways to disseminate important surgical information
      to nonsurgeons seems warranted. 

PMID- 25760209
TI  - Laparoscopic shunt revision avoids many complications of open shunt revision and
      has outcomes similar to first-time shunt placement.
AB  - Open revision of abdominal shunts is associated with increased risk of wound
      infection, visceral injury, hernia, and shunt complications. We hypothesized that
      laparoscopic revision mitigates these risks to a level similar to initial (i.e.,
      first-time) shunt placement. This was a single-center, multisurgeon,
      retrospective cohort study of patients who underwent either laparoscopic initial
      shunt placement or laparoscopic shunt revision over a 5-year period. Outcomes
      were operative time, length of stay, and 30-day complication rate. Sixty-nine
      patients underwent laparoscopic shunt revision and 99 patients underwent
      laparoscopic initial shunt placement. Operative times were nearly identical (75
      vs 73 minutes, P = 0.63). There were no significant differences in blood loss or
      hospital length of stay. Abdominal complications and total complications did not
      differ between groups. Laparoscopic shunt revision avoided many of the known
      complications of open shunt revision and had outcomes similar to initial
      laparoscopic shunt placement. 

PMID- 25760210
TI  - A single-center experience and review of the literature: 64 cases of phyllodes
      tumors to better understand risk factors and disease management.
AB  - Phyllodes tumors of the breast are rare fibroepithelial tumors that are
      characterized as benign, borderline, or malignant based on cellular
      characteristics such as stromal overgrowth and number of mitoses. Currently,
      there is a lack of consensus on risk factors and management of patients with
      phyllodes tumors, which has led to variation in treatment patterns as well as
      patient outcomes across many institutions. This study seeks to understand the
      clinicopathologic features, risk factors for local and metastatic recurrence, and
      clinical outcomes of patients with phyllodes tumors to better define optimal
      treatment patterns. 

PMID- 25760211
TI  - Perioperative and oncologic outcomes of single-incision laparoscopy compared with
      conventional laparoscopy for colon cancer: an observational propensity score
      matched study.
AB  - Single-incision laparoscopic (SIL) surgery is a recent advance in minimally
      invasive surgical techniques. From May 2011 to August 2012, 77 patients underwent
      primary SIL surgery for colon cancer by one colorectal surgeon. Among them, 61
      patients were one-to-one-matched to control patients who had undergone
      conventional laparoscopic (CL) surgery with a propensity-matched score, and the
      outcomes were compared. Two hundred forty-seven patients with colon cancer
      underwent radical colectomy. Of these, 77 patients underwent SIL colectomy. After
      matching, there were no significant differences in the general characteristics
      between the patients undergoing the two types of surgery. Operation time was
      significantly longer in SIL surgery (139 vs 121 minutes, P = 0.001), but
      procedure time (107 vs 99 minutes, P = 0.069) was not significantly longer than
      CL surgery after eliminating closure time (31 vs 22 minutes, P < 0.001) from the
      operation time. There was no significant difference in postoperative
      complications between the two groups (3.3 vs 1.6%, P = 1.000). The mean number of
      harvested lymph nodes was 23 and 22 for SIL and CL surgery, respectively (P =
      0.332). The mean follow-up period was 15.7 for the SIL group and 21.4 months for
      the CL group (P < 0.001) with two recurrences in the SIL group (3.3%) and three
      recurrences in the CL group (4.9%, P = 1.000). Disease-free survival at 20 months
      did not differ significantly between the two groups (93.3 vs 94.7%, P = 0.939).
      SIL for colonic malignancy can be safely applied for various types of operations
      and can provide equivalent oncologic resection and perioperative outcomes
      compared with CL surgery. 

PMID- 25760212
TI  - Penetrating cardiac injuries at a Level II trauma center: a 15-year review.

PMID- 25760213
TI  - Jet Ski rectal injuries: a tertiary trauma center experience.

PMID- 25760214
TI  - Firearm assault injuries in the United States: are we making progress?

PMID- 25760215
TI  - Proliferative retinopathies: animal models and therapeutic opportunities.
AB  - Proliferative retinopathies are the leading causes of blindness in Western
      societies. The development of new, more efficacious treatments that take
      advantage of recent advances in the fields of gene and cell therapy requires
      further investigations on the mechanisms underlying disease onset and
      progression, and adequate animal models that recapitulate the pathogenesis of
      human proliferative retinopathy and allow evaluation of the long-term therapeutic
      benefits that these therapies can offer. Unfortunately, most models of retinal
      neovascularization have short-term evolution and diabetic rodents show a very
      mild retinal phenotype, limited to non-proliferative changes, and do not develop
      proliferative retinopathy at all. Transgenic mice overexpressing Insulin-like
      Growth Factor-I (IGF-I) in the retina (TgIGF-I) constitute the only rodent model
      currently available that develops most of the retinal alterations observed in
      diabetic eyes, with a temporal evolution that resembles that of the human
      disease. TgIGF-I have retinal vascular alterations that progress as animals age
      from non-proliferative to proliferative disease, making these mice an excellent
      model of proliferative retinopathy that, due to its slow progression, allows long
      term evaluation of novel antiangiogenic therapies. At the molecular level,
      transgenic retinas recapitulate a variety of changes that are also observed in
      diabetic retinas, which reinforces the validity of this model. In addition to
      vascular and glial alterations, Tg-IGF-I mice show progressive neurodegeneration
      that leads to blindness in old animals. Thus, TgIGF-I are a useful model for
      testing the long-term efficacy and safety of innovative antiangiogenic, glial
      modulating and neuroprotective therapies for the treatment of diabetic
      retinopathy and other retinal proliferative disorders. 

PMID- 25760216
TI  - Is there a pulse wave encephalopathy component to multiple sclerosis?
AB  - The dominant hypothesis in multiple sclerosis is that it is an autoimmune
      disease; however, there is considerable evidence that the immune attack on myelin
      may be secondary to a cytodegenerative event. Furthermore, the immune modulating
      therapies longest in clinical use, although modulating the frequency and severity
      of exacerbation, do not affect long-term progression towards disability. Clearly
      alternative perspectives on the etiology of multiple sclerosis are warranted. In
      this paper I outline the commonalities between idiopathic normal pressure
      hydrocephalus and multiple sclerosis. These include decreased intracranial
      compliance as evidenced by increased cerebrospinal fluid volume and velocity of
      cerebrospinal fluid flow through the cerebral aqueduct; increased ventricular
      volume; periventricular demyelination lesions; increase in size of Virchow-Robin
      spaces; presence of Hakim's triad comprised of locomotory disabilities, cognitive
      problems and bladder control problems. Furthermore, multiple sclerosis is
      associated with decreased arterial compliance. These are all suggestive that
      there is a pulse wave encephalopathy component to multiple sclerosis. There are
      enough resemblances between normal pressure hydrocephalus and multiple sclerosis
      to warrant further investigation. Whether decreases in intracranial compliance is
      a consequence of multiple sclerosis or is a causal factor is unknown. Effective
      therapies can only be developed when the etiology of the disease is understood. 

PMID- 25760217
TI  - Granulocyte colony-stimulating factor and bone marrow mononuclear cells for
      stroke treatment in the aged brain.
AB  - Ischemic stroke swiftly induces a wide spectrum of pathophysiological sequelae,
      particularly in the aged brain. The translational failure of experimental
      therapies, might partially be related to monotherapeutic approaches, not address
      potential counter-mechanisms sufficiently or within the best time window. For
      example, therapeutic effects relying on stem/progenitor cell mobilization by
      granulocyte-colony stimulating factor (G-CSF), require approximately a week to
      become manifest, which is potentially beyond the optimal timing. Here, We tested
      the hypothesis that treating post-stroke aged rats with the combination of bone
      marrow-derived mononuclear cells (BM MNC) and G-CSF improves the long term (56
      days) functional outcome by compensating the delay before G-CSF effects come to
      full effect. 1x10(6) syngeneic BM MNC per kg bodyweight (BW) with G-CSF (50
      ug/kg, given intraperitoneal by via the jugular vein to aged Sprague- Dawley
      rats, six hours post-stroke. This process was repeated daily, for a 28 day
      period. Infarct volume was measured by magnetic resonance imaging at 3 and 48
      days post-stroke and additionally by immunohistochemistry at day 56. Functional
      recovery was tested during the entire post-stroke survival period. Daily G-CSF
      treatment led to a robust and consistent improvement of neurological function,
      but did not alter final infarct volumes. The combination of G-CSF and BM MNC, did
      not further improve post-stroke recovery. The lack of an additional benefit may
      be due to interaction between both approaches, and to a lesser extent, in the
      insensitivity of the aged brains' regenerative mechanisms. Also considering
      recent findings on other tandem approaches involving G-CSF in animal models
      featuring relevant co-morbidities, we conclude that such combination therapies
      are not the optimal approach to treat the acutely injured aged brain.

PMID- 25760218
TI  - Obesity promotes oxidative stress and exacerbates sepsis-induced brain damage.
AB  - Sepsis is a severe clinical syndrome in which a system-wide inflammatory response
      follows initial attempts to eliminate pathogens. It is not novel that in sepsis
      the brain is one of the first organs affected which causes an increase in
      morbidity and mortality and its consequences may be exacerbated when associated
      with a diagnosis of chronic inflammation, such as in obesity. Thus, the aim of
      the present study is to evaluate the susceptibility to brain damage after sepsis
      in obese rats. During two months, Wistar rats, 60 days, 250-300g received
      hypercaloric nutrition to induce obesity. Sepsis was submitted to the cecal
      ligation and perforation (CLP) procedure and sham-operated rats was considered
      control group. The experimental groups were divided into Sham + Eutrophic, Sham +
      Obesity, CLP + Eutrophic and CLP + Obesity. Twelve and twenty four hours after
      surgery the blood brain barrier (BBB) permeability, nitrite/nitrate
      concentration, myeloperoxidase (MPO) activity, oxidative damage to lipids and
      proteins and superoxide dismutase (SOD) and catalase (CAT) activities were
      evaluated in the hippocampus, cortex and prefrontal cortex. The data indicate
      that in obese rats subjected to sepsis occurs an increase of BBB permeability in
      different brain regions compared to eutrophic septic rats. This alteration
      reflected an increase of MPO activity, concentration of nitrite/nitrate,
      oxidative damage to lipids and proteins and an imbalance of SOD and CAT
      especially 24 hours after sepsis. It follows that obesity due to its pro
      inflammatory phenotype can aggravate or accelerate the sepsis-induced damage in
      rat brain. 

PMID- 25760219
TI  - Etanercept improves cognitive performance and increases eNOS and BDNF expression
      during experimental vascular dementia in streptozotocin-induced diabetes.
AB  - Diabetes mellitus (DM) is related to an increase in the incidence of vascular
      dementia. Inflammation is an important cause of endothelial dysfunction and
      cognitive deficits. The anti -tumor necrosis factor (TNF)-alpha fusion protein
      etanercept has been reported to exhibit memory-enhancing effects and endothelial
      protection. We tested the effect of etanercept on the cognitive endpoints and
      compared it with the cognitive dysfunction in streptozotocin (STZ )- induced DM
      rats by using the Morris water maze test (MWMT) and passive avoidance test (PAT).
      Systolic blood pressure (SBP), thoracic endothelial function, endothelial nitric
      oxide synthase (eNOS) expression, and hippocampal brain-derived neurotrophic
      factor (BDNF) expression were assessed. Thirty days after the induction of DM,
      rats exhibited severe learning and memory deficits associated with endothelial
      dysfunction and decreased expression of eNOS and BDNF. Chronic treatment with
      etanercept (0.8 mg/kg, s.c., every week for 30 days) improved cognitive
      performance, endothelial function, and expression of eNOS and BDNF in DM rats.
      Furthermore, the memory-improving effects of etanercept were independent of
      hyperglycemia. These data suggest that etanercept treatment prevents changes in
      endothelial function, eNOS expression, and hippocampal expression of BDNF and,
      consequently, vascular dementia in DM rats. 

PMID- 25760220
TI  - An experimental model for exudative age-related macular degeneration with
      choroidal neovascularization using the common marmoset.
AB  - This study aimed to establish an experimental exudative age-related macular
      degeneration (AMD) model in the common marmoset (Callithrix jacchus), which is a
      small New World monkey. Choroidal neovascularization (CNV) was induced by laser
      irradiation on the left eye of each animal under anesthesia. Eight laser spots
      were applied around the macular area using the image-guided laser system (532 nm)
      attached with Micron III at 650 mW-2,000 mW power. Laser pulse duration and spot
      size were fixed at 100 ms and 50 um, respectively. At 14 days after laser
      irradiation, fluorescein angiograms were observed. At 21 days after laser
      irradiation, the fluorescein angiograms were transcardially perfused to the
      bilateral common carotid arteries with 4% paraformaldehyde for the transverse
      section or with fluorescein-conjugated dextran (MW = 2,000 kDa) for the retinal
      pigment epithelia (RPE)-choroidal flatmount. At 14 days after laser irradiation,
      late hyperfluorescence and leakage within or beyond the lesion borders were
      observed in a laser power-dependent manner. In the RPE-choroidal flatmount, the
      mean size of the CNV lesions at 1,500 mW was 1.34 +/- 0.49 * 10(5) um(2) (Mean +/
      S.D., n = 29), and the coefficient of variation for each CNV area was 36.5% (n =
      29). In conclusion, we succeeded in producing an experimental exudative type of
      AMD model in the common marmoset. This model may be useful in elucidating the
      pathophysiological mechanism and screening of new candidates for exudative AMD. 

PMID- 25760221
TI  - Uric acid and Cu/Zn superoxide dismutase: potential strategies and biomarkers in
      functional recovery of post-acute ischemic stroke patients after intensive
      neurorehabilitation.
AB  - No evidence is currently provided on the involvement of uric acid (UA) and Cu/Zn
      Superoxide Dismutase (Cu/Zn SOD) in functional recovery of stroke patients after
      neurorehabilitation. For this purpose, the relationship between UA and Cu/Zn SOD
      plasma levels and clinical and functional outcome measures were analysed in
      twenty-five post-acute stroke patients undergoing intensive neurorehabilitation.
      UA and Cu/Zn SOD plasma levels were evaluated in fifteen healthy subjects as
      control values. Neurorehabilitation was associated with improved scores (P<0.05)
      of the National Institutes of Health Stroke Scale (NIHSS), the modified Rankin
      Scale (mRS), and the mPULSES profile. UA plasma levels were higher before
      neurorehabilitation, decreased after, but were still higher than control values.
      Conversely, Cu/Zn SOD plasma levels were lower than control values before
      neurorehabilitation and increased after, even though the absolute values were
      still lower than controls. An inverse correlation was found between variations of
      UA plasma levels observed before and after neurorehabilitation (Delta UA) and
      those of Cu/Zn SOD (Delta Cu/Zn SOD) (r= -0.386; P<0.001). No significant
      correlations were observed between DeltaUA and the variations of the scores
      observed in all clinical outcome measures before and after neurorehabilitation
      (Delta scores of clinical outcome measures). Delta Cu/Zn SOD correlated
      positively with Delta NIHSS, Delta mRS and Delta mPULSES scores. Our data provide
      evidence of neurorehabilitation effectiveness on modulating UA and Cu/Zn SOD
      plasma levels and suggest that Cu/Zn SOD could assume the significance of
      biomarker of functional recovery, rather than UA that could be a marker of the
      magnitude of oxidative injury. 

PMID- 25760222
TI  - Paring down obesity and metabolic disease by targeting inflammation and oxidative
      stress.

PMID- 25760223
TI  - Relationships between antibiotics and antibiotic resistance gene levels in
      municipal solid waste leachates in Shanghai, China.
AB  - Many studies have quantified antibiotics and antibiotic resistance gene (ARG)
      levels in soils, surface waters, and waste treatment plants (WTPs). However,
      similar work on municipal solid waste (MSW) landfill leachates is limited, which
      is concerning because antibiotics disposal is often in the MSW stream. Here we
      quantified 20 sulfonamide (SA), quinolone (FQ), tetracycline (TC), macrolide
      (ML), and chloramphenicol (CP) antibiotics, and six ARGs (sul1, sul2, tetQ, tetM,
      ermB, and mefA) in MSW leachates from two Shanghai transfer stations (TS; sites
      Hulin (HL) and Xupu (XP)) and one landfill reservoir (LR) in April and July 2014.
      Antibiotic levels were higher in TS than LR leachates (985 +/- 1965 ng/L vs 345
      +/- 932 ng/L, n = 40), which was because of very high levels in the HL leachates
      (averaging at 1676 +/- 5175 ng/L, n = 40). The mean MLs (3561 +/- 8377 ng/L, n =
      12), FQs (975 +/- 1608 ng/L, n = 24), and SAs (402 +/- 704 ng/L, n = 42) classes
      of antibiotics were highest across all samples. ARGs were detected in all
      leachate samples with normalized sul2 and ermB levels being especially elevated (
      1.37 +/- 1.2 and -1.76 +/- 1.6 log (copies/16S-rDNA), respectively). However, ARG
      abundances did not correlate with detected antibiotic levels, except for tetW and
      tetQ with TC levels (r = 0.88 and 0.81, respectively). In contrast, most measured
      ARGs did significantly correlate with heavy metal levels (p < 0.05), especially
      with Cd and Cr. This study shows high levels of ARGs and antibiotics can prevail
      in MSW leachates and landfills may be an underappreciated as a source of
      antibiotics and ARGs to the environment. 

PMID- 25760224
TI  - Inhibition of Forkhead box protein M1 by thiostrepton increases chemosensitivity
      to doxorubicin in T-cell acute lymphoblastic leukemia.
AB  - T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive type of blood
      malignancy, deriving from T-cell progenitors in the thymus, and comprises 10-15%
      of pediatric and 25% of adult primary ALL cases. Despite advances, 20% of
      pediatric and the majority of adult patients with T-ALL succumb to mortality from
      resistant or relapsed disease, and the survival rate for patients with resistant
      or relapsed T-ALL remains poor. Alterations in the expression of Forkhead box
      protein M1 (FoxM1) have been detected in several types of cancer, and the
      inhibition of FoxM1 has been investigated as therapeutic strategy in cancer. The
      present study investigated the effects of the inhibition of FoxM1 by thiostrepton
      in human T-ALL Jurkat cells. The cells were treated with different concentrations
      of thiostrepton, either alone or in combination with doxorubicin. Cell viability
      was measured using CCK-8 assays and the cell cycle distribution, apoptosis and
      cell-associated mean fluorescence intensity of intracellular doxorubicin were
      assessed using flow cytometric analysis. The mRNA and protein expression levels
      were detected by reverse transcription-quantitative polymerase chain reaction and
      western blot analyses. The inhibition of FoxM1 by thiostrepton significantly
      decreased the proliferation of the Jurkat cells proliferation in a time- and dose
      dependent manner. Cell arrest at the G2/M phase, and apoptosis was significantly
      increased in the thiostrepton-treated Jurkat cells. Thiostrepton reduced the half
      maximal inhibitory concentration of doxorubicin in the Jurkat cells, and
      significantly enhanced the cytotoxicity of doxorubicin within the Jurkat cells by
      enhancing doxorubicin-induced apoptosis and increasing the accumulation of
      intracellular doxorubicin. Furthermore, the inhibition of FoxM1 by thiostrepton
      enhanced doxorubicin-induced apoptosis, possibly through a caspase-3-dependent
      pathway, and increased the accumulation of intracellular doxorubicin, possibly
      through downregulating the expression of glutathione S-transferase pi.
      Collectively, the results of the present study suggested that targeting FoxM1
      with thiostrepton resulted in potent antileukemia activity and chemosensitizing
      effects in human T-ALL Jurkat cells.

PMID- 25760225
TI  - From solution to gas phase: the implications of intramolecular interactions on
      the evaporative dynamics of substance P during electrospray ionization.
AB  - Substance P (RPKPQQFFGLM-NH2) [M + 3H](3+) ions have been shown to occupy two
      distinct conformer states, a compact population of conformers that is formed by
      evaporation of hydrated ions, and an elongated population of conformers that is
      formed by collisional heating of the compact conformer. Molecular dynamics (MD)
      simulations and amino acid mutations revealed that the compact conformer is
      stabilized by intramolecular interactions between the localized charge-carrying
      sites, specifically the N-terminus, R(1), and K(3), with the side chains of
      glutamine and phenylalanine residues present in the peptide. Here, we employ
      amino acid mutations and cryogenic ion mobility-mass spectrometry (cryo-IM-MS) in
      an effort to understand how eliminating specific intramolecular interactions
      alters ion hydration, as well as the dehydration dynamics of substance P during
      the final stages of the electrospray process. The results clearly illustrate a
      direct link between the stabilizing effects of intramolecular self-solvation and
      the formation of substance P [M + 3H](3+) ions. Most notably, removal of these
      stabilizing interactions leads to a reduction in the abundances of [M + 3H](3+)
      ions induced by charge reduction reactions, i.e., loss of H(+)(H2O)n ions to form
      [M + 2H](2+) ions during the final stages of the electrospray process. 

PMID- 25760227
TI  - Direct detection of a triplet vinylnitrene, 1,4-naphthoquinone-2-ylnitrene, in
      solution and cryogenic matrices.
AB  - The photolysis of 2-azido-1,4-naphthoquinone (1) in argon matrices at 8 K results
      in the corresponding triplet vinylnitrene (3)2, which was detected directly by IR
      spectroscopy. Vinylnitrene (3)2 is stable in argon matrices but forms 2
      cyanoindane-1,3-dione (3) upon further irradiation. Similarly, the irradiation of
      azide 1 in 2-methyltetrahydrofuran (MTHF) matrices at 5 K resulted in the ESR
      spectrum of vinylnitrene (3)2, which is stable up to at least 100 K. The zero
      field splitting parameters for nitrene (3)2, D/hc = 0.7292 cm(-1) and E/hc =
      0.0048 cm(-1), verify that it has significant 1,3-biradical character.
      Vinylnitrene (3)2 (lambdamax ~ 460 nm, tau = 22 MUs) is also observed directly in
      solution at ambient temperature with laser flash photolysis of 1. Density
      functional theory (DFT) calculations support the characterization of vinylnitrene
      (3)2 and the proposed mechanism for its formation. Because vinylnitrene (3)2 is
      relatively stable, it has potential use as a building-block for high-spin
      assemblies. 

PMID- 25760226
TI  - Polymer directed self-assembly of pH-responsive antioxidant nanoparticles.
AB  - We have developed pH-responsive, multifunctional nanoparticles based on
      encapsulation of an antioxidant, tannic acid (TA), using flash nanoprecipitation,
      a polymer directed self-assembly method. Formation of insoluble coordination
      complexes of tannic acid and iron during mixing drives nanoparticle assembly.
      Tuning the core material to polymer ratio, the size of the nanoparticles can be
      readily tuned between 50 and 265 nm. The resulting nanoparticle is pH-responsive,
      i.e., stable at pH 7.4 and soluble under acidic conditions due to the nature of
      the coordination complex. Further, the coordination complex can be coprecipitated
      with other hydrophobic materials such as therapeutics or imaging agents. For
      example, coprecipitation with a hydrophobic fluorescent dye creates fluorescent
      nanoparticles. In vitro, the nanoparticles have low cytotoxicity and show
      antioxidant activity. Therefore, these particles may facilitate intracellular
      delivery of antioxidants. 

PMID- 25760228
TI  - Two birds with one stone.

PMID- 25760229
TI  - Effects of glucose-dependent insulinotropic polypeptide receptor knockout and a
      high-fat diet on cognitive function and hippocampal gene expression in mice.
AB  - It has been previously demonstrated that compromise of glucose-dependent
      insulinotropic polypeptide receptor (GIPR) action and chronic consumption of a
      high-fat diet can independently impair memory and learning ability, however, the
      underlying pathology remain to be elucidated. The present study investigated the
      effects of GIPR knockout (KO), alone and in combination with a high-fat diet, on
      aspects of cognitive function and hippocampal gene expression in mice. In object
      recognition tests, normal mice exhibited effective memory, preferring to
      investigate the novel over the familiar object. However, wild-type (WT) mice fed
      a high-fat diet and GIPR KO mice fed a standard or high-fat diet demonstrated no
      such discrimination, suggesting the impairment of memory function. This decline
      in cognitive function was associated with marked changes in the expression levels
      of hippocampal genes involved in memory and learning. The chronic consumption of
      a high-fat diet decreased the hippocampal gene expression levels of mammalian
      target of rapamycin (mTOR), neurotrophic tyrosine kinase receptor type 2 (NTRK2)
      and synaptophysin. Notably, the GIPR KO mice fed a high-fat diet exhibited no
      reduction in the hippocampal expression of synaptophysin expression, however, the
      GIPR KO mice fed a standard rodent maintenance diet exhibited reduced hippocampal
      expression of mTOR compared with the WT controls. These data highlighted the
      importance of intact GIPR signalling and dietary composition in modulating memory
      and learning, and hippocampal pathways involved in the maintenance of synaptic
      plasticity, including mTOR and NTRK2, appear to be key in this regard.

PMID- 25760231
TI  - Broadband light trapping in thin film solar cells with self-organized plasmonic
      nano-colloids.
AB  - The intense light scattered from metal nanoparticles sustaining surface plasmons
      makes them attractive for light trapping in photovoltaic applications. However, a
      strong resonant response from nanoparticle ensembles can only be obtained if the
      particles have monodisperse physical properties. Presently, the chemical
      synthesis of colloidal nanoparticles is the method that produces the highest
      monodispersion in geometry and material quality, with the added benefits of being
      low-temperature, low-cost, easily scalable and of allowing control of the surface
      coverage of the deposited particles. In this paper, novel plasmonic back
      reflector structures were developed using spherical gold colloids with
      appropriate dimensions for pronounced far-field scattering. The plasmonic back
      reflectors are incorporated in the rear contact of thin film n-i-p
      nanocrystalline silicon solar cells to boost their photocurrent generation via
      optical path length enhancement inside the silicon layer. The quantum efficiency
      spectra of the devices revealed a remarkable broadband enhancement, resulting
      from both light scattering from the metal nanoparticles and improved light
      incoupling caused by the hemispherical corrugations at the cells' front surface
      formed from the deposition of material over the spherically shaped colloids. 

PMID- 25760230
TI  - Association between serum concentrations of hypoxia inducible factor responsive
      proteins and excessive erythrocytosis in high altitude Peru.
AB  - Painschab, Matthew S., Gary E. Malpartida, Victor G. Davila-Roman, Robert H.
      Gilman, Todd M. Kolb, Fabiola Leon-Velarde, J. Jaime Miranda, and William
      Checkley. Association between serum concentrations of hypoxia inducible factor
      responsive proteins and excessive erythrocytosis in high altitude Peru. High Alt
      Med Biol 16:26-33, 2015.-Long-term residence at high altitude is associated with
      the development of chronic mountain sickness (CMS), which is characterized by
      excessive erythrocytosis (EE). EE occurs under chronic hypoxia, and a strongly
      selected mutation in hypoxia-inducible factor 2alpha (HIF2A) has been found in
      native Tibetans that correlates with having a normal hemoglobin at high altitude.
      We sought to evaluate differences in plasma levels of four HIF-responsive
      proteins in 20 participants with EE (hemoglobin >21 g/dL in men and >19 in women)
      and in 20 healthy, age- and sex-matched participants without EE living at high
      altitude in Puno, Peru. We performed ELISA to measure plasma levels of the four
      HIF-responsive proteins: vascular endothelial growth factor (VEGF), soluble VEGF
      receptor 1 (sVEGF-R1), endothelin-1, and erythropoietin. As a secondary aim, we
      evaluated the association between HIF-responsive proteins and echocardiography
      estimated pulmonary artery systolic pressure (PASP) in a subset of 26
      participants. sVEGF-R1 was higher in participants with vs. without EE (mean 107
      pg/mL vs. 90 pg/mL; p=0.007). Although plasma concentrations of endothelin-1,
      VEGF, and erythropoietin were higher in participants with vs. without EE, they
      did not achieve statistical significance (all p>0.25). Both sVEGF-R1 (p=0.04) and
      erythropoietin (p=0.04) were positively associated with PASP after adjustment for
      age, sex, and BMI. HIF-responsive proteins may play a pathophysiological role in
      altitude-related, chronic diseases but our results did not show consistent
      changes in all measured HIF-responsive proteins. Larger studies are needed to
      evaluate for additional genetic and environmental risk factors.

PMID- 25760232
TI  - Levels of dissociation and nonsuicidal self-injury: a quartile risk model.
AB  - Extant research indicates that dissociation may act as a risk factor for
      nonsuicidal self-injury (NSSI), but the data are mixed. In this study, 75
      university and community females ages 18-35 were assessed for rates of normative,
      clinical, and severely clinical dissociation as well as for NSSI. Significant
      differences in normative dissociation were found between the control group and
      the group reporting a history of NSSI. In addition, normative dissociation--but
      not clinical or severely clinical dissociation--was found to be significantly
      associated with NSSI in this sample. Considering this finding in the context of
      the existing literature, we propose a quartile risk model of dissociation and
      NSSI as a new approach to the influences of levels of dissociation on NSSI risk.

PMID- 25760233
TI  - Identification and function analysis of contrary genes in Dupuytren's
      contracture.
AB  - The present study aimed to analyze the expression of genes involved in
      Dupuytren's contracture (DC), using bioinformatic methods. The profile of
      GSE21221 was downloaded from the gene expression ominibus, which included six
      samples, derived from fibroblasts and six healthy control samples, derived from
      carpal-tunnel fibroblasts. A Distributed Intrusion Detection System was used in
      order to identify differentially expressed genes. The term contrary genes is
      proposed. Contrary genes were the genes that exhibited opposite expression
      patterns in the positive and negative groups, and likely exhibited opposite
      functions. These were identified using Coexpress software. Gene ontology (GO)
      function analysis was conducted for the contrary genes. A network of GO terms was
      constructed using the reduce and visualize gene ontology database. Significantly
      expressed genes (801) and contrary genes (98) were screened. A significant
      association was observed between Chitinase-3-like protein 1 and ten genes in the
      positive gene set. Positive regulation of transcription and the activation of
      nuclear factor-kappaB (NF-kappaB)-inducing kinase activity exhibited the highest
      degree values in the network of GO terms. In the present study, the expression of
      genes involved in the development of DC was analyzed, and the concept of contrary
      genes proposed. The genes identified in the present study are involved in the
      positive regulation of transcription and activation of NF-kappaB-inducing kinase
      activity. The contrary genes and GO terms identified in the present study may
      potentially be used for DC diagnosis and treatment.

PMID- 25760234
TI  - Multicomponent signal unmixing from nanoheterostructures: overcoming the
      traditional challenges of nanoscale X-ray analysis via machine learning.
AB  - The chemical composition of core-shell nanoparticle clusters have been determined
      through principal component analysis (PCA) and independent component analysis
      (ICA) of an energy-dispersive X-ray (EDX) spectrum image (SI) acquired in a
      scanning transmission electron microscope (STEM). The method blindly decomposes
      the SI into three components, which are found to accurately represent the
      isolated and unmixed X-ray signals originating from the supporting carbon film,
      the shell, and the bimetallic core. The composition of the latter is verified by
      and is in excellent agreement with the separate quantification of bare bimetallic
      seed nanoparticles. 

PMID- 25760235
TI  - Crystal Structure of Human Profilaggrin S100 Domain and Identification of Target
      Proteins Annexin II, Stratifin, and HSP27.
AB  - The fused-type S100 protein profilaggrin and its proteolytic products including
      filaggrin are important in the formation of a normal epidermal barrier; however,
      the specific function of the S100 calcium-binding domain in profilaggrin biology
      is poorly understood. To explore its molecular function, we determined a 2.2 A
      resolution crystal structure of the N-terminal fused-type S100 domain of human
      profilaggrin with bound calcium ions. The profilaggrin S100 domain formed a
      stable dimer, which contained two hydrophobic pockets that provide a molecular
      interface for protein interactions. Biochemical and molecular approaches
      demonstrated that three proteins, annexin II/p36, stratifin/14-3-3 sigma, and
      heat shock protein 27, bind to the N-terminal domain of human profilaggrin; one
      protein (stratifin) co-localized with profilaggrin in the differentiating
      granular cell layer of human skin. Together, these findings suggest a model where
      the profilaggrin N-terminus uses calcium-dependent and calcium-independent
      protein-protein interactions to regulate its involvement in keratinocyte terminal
      differentiation and incorporation into the cornified cell envelope. 

PMID- 25760237
TI  - Influence of solids retention time on membrane fouling: characterization of
      extracellular polymeric substances and soluble microbial products.
AB  - The objective of this study was to investigate the influence of solids retention
      time (SRT) on membrane fouling and the characteristics of biomacromolecules. Four
      identical laboratory-scale membrane bioreactors (MBRs) were operated with SRTs
      for 10, 20, 40 and 80 days. The results indicated that membrane fouling occurred
      faster and more readily under short SRTs. Fouling resistance was the primary
      source of filtration resistance. The modified fouling index (MFI) results
      suggested that the more ready fouling at short SRTs could be attributed to higher
      concentrations of soluble microbial products (SMP). Fourier transform infrared
      (FTIR) spectra indicated that the SRT had a weak influence on the functional
      groups of the total extracellular polymeric substances (TEPS) and SMP. However,
      the MBR under a short SRT had more low-molecular-weight (MW) compounds (<1 kDa)
      and fewer high-MW compounds (>100 kDa). Aromatic protein and tryptophan protein
      like substances were the dominant groups in the TEPS and SMP, respectively. 

PMID- 25760238
TI  - Hearing assessment data in HIV-infected and uninfected children of Cape Town,
      South Africa.
AB  - Researchers are showing that the rate of hearing loss in children with perinatal
      HIV infection (PHIV) is higher than in HIV-unexposed, uninfected children. These
      data, however, have been collected mostly in the USA; extensive hearing data from
      low- and middle-income countries are lacking. The purpose of this study was to
      collect audiometric data in PHIV and HIV-uninfected children living in Cape Town,
      South Africa. Questionnaire data along with distortion product otoacoustic
      emissions (DPOAEs) and pure-tone testing were completed. Hearing loss was
      determined using the pure-tone thresholds defined as a pure-tone average (PTA) of
      500, 1000, 2000, and 4000 Hz of >15 dB HL in the poorer ear. All data were
      compared between PHIV and HIV-uninfected children. Sixty-one (37 PHIV and 24 HIV
      uninfected) children had hearing data. HIV status was not significantly
      associated with DPOAEs. The rate of conductive hearing loss was 11.5%; five PHIV
      and two HIV-uninfected children. The rate of any hearing loss was higher in PHIV
      children, but this difference was not statistically significant. PHIV children
      had a significantly higher mean PTA in the poorer ear than HIV-uninfected
      children. Conductive type of hearing loss was more common than sensorineural
      hearing loss. The underlying cause of hearing loss in the present study therefore
      remains unclear. Future research should include an examination of auditory neural
      function in an effort to determine the possible reason for differences in
      hearing. 

PMID- 25760236
TI  - Poly(gamma-Glutamic Acid) as an Exogenous Promoter of Chondrogenic
      Differentiation of Human Mesenchymal Stem/Stromal Cells.
AB  - Cartilage damage and/or aging effects can cause constant pain, which limits the
      patient's quality of life. Although different strategies have been proposed to
      enhance the limited regenerative capacity of cartilage tissue, the full
      production of native and functional cartilaginous extracellular matrix (ECM) has
      not yet been achieved. Poly(gamma-glutamic acid) (gamma-PGA), a naturally
      occurring polyamino acid, biodegradable into glutamate residues, has been
      explored for tissue regeneration. In this work, gamma-PGA's ability to support
      the production of cartilaginous ECM by human bone marrow mesenchymal stem/stromal
      cells (MSCs) and nasal chondrocytes (NCs) was investigated. MSC and NC pellets
      were cultured in basal medium (BM), chondrogenic medium (CM), and CM-gamma-PGA
      supplemented medium (CM+gamma-PGA) over a period of 21 days. Pellet size/shape
      was monitored with time. At 14 and 21 days of culture, the presence of sulfated
      glycosaminoglycans (sGAGs), type II collagen (Col II), Sox-9, aggrecan, type XI
      collagen (Col XI), type X collagen (Col X), calcium deposits, and type I collagen
      (Col I) was analyzed. After excluding gamma-PGA's cytotoxicity, earlier cell
      condensation, higher sGAG content, Col II, Sox-9 (day 14), aggrecan, and Col X
      (day 14) production was observed in gamma-PGA-supplemented MSC cultures, with no
      signs of mineralization or Col I. These effects were not evident with NCs.
      However, Sox-9 (at day 14) and Col X (at days 14 and 21) were increased,
      decreased, or absent, respectively. Overall, gamma-PGA improved chondrogenic
      differentiation of MSCs, increasing ECM production earlier in culture. It is
      proposed that gamma-PGA incorporation in novel biomaterials has a beneficial
      impact on future approaches for cartilage regeneration. 

PMID- 25760239
TI  - Pericoronary adipose tissue: a novel therapeutic target in obesity-related
      coronary atherosclerosis.
AB  - Inflammation plays a crucial role in the development and destabilization of
      atherosclerotic plaques in coronary vessels. Adipose tissue is considered to act
      in paracrine manner, which modulates a number of physiological and
      pathophysiological processes. Perivascular adipose tissue has developed specific
      properties that distinguish it from the fat in other locations. Interestingly,
      its activity depends on several metabolic conditions associated with insulin
      resistance and weight gain. Particularly in obesity perivascular fat seems to
      change its character from a protective to a detrimental one. The present review
      analyzes literature in terms of the pathophysiology of atherosclerosis, with
      particular emphasis on inflammatory processes. Additionally, the authors
      summarize data about confirmed paracrine activity of visceral adipose tissue and
      especially about pericoronary fat influence on the vascular wall. The
      contribution of adiponectin, leptin and resistin is addressed. Experimental and
      clinical data supporting the thesis of outside-to-inside signaling in the
      pericoronary milieu are further outlined. Clinical implications of epicardial and
      pericoronary adipose tissue activity are also evaluated. The role of pericoronary
      adipose tissue in obesity-related atherosclerosis is highlighted. In conclusion,
      the authors discuss potential therapeutical implications of these novel
      phenomena, including adipokine imbalance in pericoronary adipose tissue in the
      setting of obesity, the influence of lifestyle and diet modification,
      pharmaceutical interventions and the growing role of microRNAs in adipogenesis,
      insulin resistance and obesity. Key teaching points: * adipose tissue as a source
      of inflammatory mediators * changes in the vascular wall as a result of outside
      to-inside signaling * anatomy, physiology, and clinical implications of
      epicardial and pericoronary adipose tissue activity * adipokines and their role
      in obesity-related atherosclerosis * therapeutic perspectives and future
      directions. 

PMID- 25760240
TI  - Videos in clinical medicine. Putting on and removing personal protective
      equipment.

PMID- 25760241
TI  - Molecular determinants of drug-specific sensitivity for epidermal growth factor
      receptor (EGFR) exon 19 and 20 mutants in non-small cell lung cancer.
AB  - We hypothesized that aberrations activating epidermal growth factor receptor
      (EGFR) via dimerization would be more sensitive to anti-dimerization agents
      (e.g., cetuximab). EGFR exon 19 abnormalities (L747_A750del; deletes amino acids
      LREA) respond to reversible EGFR kinase inhibitors (TKIs). Exon 20 in-frame
      insertions and/or duplications (codons 767 to 774) and T790M mutations are
      clinically resistant to reversible/some irreversible TKIs. Their impact on
      protein function/therapeutic actionability are not fully elucidated.In our study,
      the index patient with non-small cell lung cancer (NSCLC) harbored EGFR
      D770_P772del_insKG (exon 20). A twenty patient trial (NSCLC cohort) (cetuximab
      based regimen) included two participants with EGFR TKI-resistant mutations ((i)
      exon 20 D770>GY; and (ii) exon 19 LREA plus exon 20 T790M mutations). Structural
      modeling predicted that EGFR exon 20 anomalies (D770_P772del_insKG and D770>GY),
      but not T790M mutations, stabilize the active dimer configuration by increasing
      the interaction between the kinase domains, hence sensitizing to an agent
      preventing dimerization. Consistent with predictions, the two patients harboring
      D770_P772del_insKG and D770>GY, respectively, responded to an EGFR antibody
      (cetuximab)-based regimen; the T790M-bearing patient showed no response to
      cetuximab combined with erlotinib. In silico modeling merits investigation of its
      ability to optimize therapeutic selection based on structural/functional
      implications of different aberrations within the same gene. 

PMID- 25760243
TI  - Deficiency of AMPK in CD8+ T cells suppresses their anti-tumor function by
      inducing protein phosphatase-mediated cell death.
AB  - A number of studies have linked AMPK, a major metabolic sensor coordinating of
      multiple cellular functions, to tumor development and progression. However, the
      exact role of AMPK in tumor development is still controversial. Here we report
      that activation of AMPK promotes survival and anti-tumor function of T cells, in
      particular CD8+ T cells, resulting in superior tumor suppression in vivo. While
      AMPK expression is dispensable for T cell development, genetic deletion of AMPK
      promotes T cell death during in vitro activation and in vivo tumor development.
      Moreover, we demonstrate that protein phosphatases are the key mediators of AMPK
      dependent effects on T cell death, and inhibition of phosphatase activity by
      okadaic acid successfully restores T cell survival and function. Altogether, our
      data suggest a novel mechanism by which AMPK regulates protein phosphatase
      activity in control of survival and function of CD8+ T cells, thereby enhancing
      their role in tumor immunosurveillance.

PMID- 25760246
TI  - Hearing Thresholds, Minimum Response Levels, and Cross-Check Measures in
      Pediatric Audiology.
AB  - PURPOSE: Pediatric audiologists must identify hearing loss in a timely manner so
      that early intervention can be provided. In this article, the methods important
      for differentiating between a hearing threshold and minimum response level (MRL),
      important for an accurate diagnosis, are described. METHOD: Operant conditioning
      procedures, used during visual reinforcement audiometry and conditioned play
      audiometry, are reviewed. Case examples are provided that demonstrate the
      importance of using evidence-based procedures, evaluating the success of such
      procedures, and using cross-check measures for interpreting responses as
      thresholds or MRLs. RESULTS: Behavioral-hearing thresholds can be obtained when
      operant conditioning procedures are successful and cross-check measures
      corroborate the audiometric results. When MRLs are obtained, cross-check measures
      are critical in determining the likelihood of hearing loss and making follow-up
      recommendations. CONCLUSIONS: Early diagnosis of hearing loss is important so
      that intervention can be initiated within critical periods during infant and
      childhood learning. Accurate diagnosis depends on the audiologist, who must
      adhere to evidence-based procedures, use cross-check measures, and evaluate the
      validity of each procedure. Future research and guidelines are needed to examine
      decision-making processes in pediatric audiology that ensure diagnostic accuracy
      and timely intervention for infants and children identified with hearing loss.

PMID- 25760242
TI  - Clinical and biological significance of de novo CD5+ diffuse large B-cell
      lymphoma in Western countries.
AB  - CD5 is a pan-T-cell surface marker and is rarely expressed in diffuse large B
      cell lymphoma (DLBCL). Large-scale studies of de novo CD5+ DLBCL are lacking in
      Western countries. In this study by the DLBCL Rituximab-CHOP Consortium, CD5 was
      expressed in 5.5% of 879 DLBCL patients from Western countries. CD5+ DLBCL was
      associated with higher frequencies of >1 ECOG performance status, bone marrow
      involvement, central nervous system relapse, activated B-cell-like subtype, Bcl-2
      overexpression, and STAT3 and NF-kappaB activation, whereas rarely expressed
      single-stranded DNA-binding protein 2 (SSBP2), CD30 or had MYC mutations. With
      standard R-CHOP chemotherapy, CD5+ DLBCL patients had significantly worse overall
      survival (median, 25.3 months vs. not reached, P< .0001) and progression-free
      survival (median, 21.3 vs. 85.8 months, P< .0001) than CD5- DLBCL patients, which
      was independent of Bcl-2, STAT3, NF-kappaB and the International Prognostic
      Index. Interestingly, SSBP2 expression abolished the prognostic significance of
      CD5 expression, suggesting a tumor-suppressor role of SSBP2 for CD5 signaling.
      Gene-expression profiling demonstrated that B-cell receptor signaling dysfunction
      and microenvironment alterations are the important mechanisms underlying the
      clinical impact of CD5 expression. This study shows the distinctive clinical and
      biological features of CD5+ DLBCL patients in Western countries and underscores
      important pathways with therapeutic implications. 

PMID- 25760245
TI  - Inhibition of the transient receptor potential melastatin-2 channel causes
      increased DNA damage and decreased proliferation in breast adenocarcinoma cells.
AB  - Transient receptor potential, melastatin-2 (TRPM2) is a plasma membrane cation
      channel with important roles in sensory functions and promoting cell death.
      However, we demonstrated here that TRPM2 was present in the nuclei of MCF-7 and
      MDA-MB-231 human breast adenocarcinoma cells, and its pharmacologic inhibition or
      RNAi silencing caused decreased cell proliferation. Neither an effect on
      proliferation nor a localization of TRPM2 in the nucleus was observed in
      noncancerous HMEC and MCF-10A human mammary epithelial cells. Investigation of
      possible effects of TRPM2 function in the nucleus demonstrated that pharmacologic
      inhibition or RNAi silencing of TRPM2 in MCF-7 and MDA-MB-231 human breast
      adenocarcinoma cells caused up to 4-fold increases in DNA damage levels, as
      compared to noncancerous breast cells after equivalent treatments. These results
      indicate that TRPM2 has a novel nuclear function in human breast adenocarcinoma
      cells that facilitates the integrity of genomic DNA, a finding that is distinct
      from its previously reported role as a plasma membrane cation channel in
      noncancerous cells. In summary, we report here a novel effect promoted by TRPM2,
      where it functions to minimize DNA damage and thus may have a role in the
      protection of genomic DNA in breast cancer cells. Our study therefore provides
      compelling evidence that TRPM2 has a unique role in breast adenocarcinoma cells.
      Accordingly, these studies suggest that TRPM2 is a potential therapeutic target,
      where its pharmacologic inhibition may provide an innovative strategy to
      selectively increase DNA damage levels in breast cancer cells.

PMID- 25760244
TI  - An assessment of bacterial small RNA target prediction programs.
AB  - Most bacterial regulatory RNAs exert their function through base-pairing with
      target RNAs. Computational prediction of targets is a busy research field that
      offers biologists a variety of web sites and software. However, it is difficult
      for a non-expert to evaluate how reliable those programs are. Here, we provide a
      simple benchmark for bacterial sRNA target prediction based on trusted E. coli
      sRNA/target pairs. We use this benchmark to assess the most recent RNA target
      predictors as well as earlier programs for RNA-RNA hybrid prediction. Moreover,
      we consider how the definition of mRNA boundaries can impact overall predictions.
      Recent algorithms that exploit both conservation of targets and accessibility
      information offer improved accuracy over previous software. However, even with
      the best predictors, the number of true biological targets with low scores and
      non-targets with high scores remains puzzling. 

PMID- 25760247
TI  - Investigation of the roles of exosomes in colorectal cancer liver metastasis.
AB  - The leading cause of death among cancer patients is tumor metastasis. Tumor
      derived exosomes are emerging as mediators of metastasis. In the present study,
      we demonstrated that exosomes play a pivotal role in the metastatic progression
      of colorectal cancer. First, a nude mouse model of colorectal cancer liver
      metastasis was established and characterized. Then, we demonstrated that exosomes
      from a highly liver metastatic colorectal cancer cell line (HT-29) could
      significantly increase the metastatic tumor burden and distribution in the mouse
      liver of Caco-2 colorectal cancer cells, which ordinarily exhibit poor liver
      metastatic potential. We further investigated the mechanisms by which HT-29
      derived-exosomes influence the liver metastasis of colorectal cancer and found
      that mice treated with HT-29-derived exosomes had a relatively higher level of
      CXCR4 in the metastatic microenvironment, indicating that exosomes may promote
      colorectal cancer metastasis by recruiting CXCR4-expressing stromal cells to
      develop a permissive metastatic microenvironment. Finally, the migration of Caco
      2 cells was significantly increased following treatment with HT-29-derived
      exosomes in vitro, further supporting a role for exosomes in modulating
      colorectal tumor-derived liver metastasis. The data from the present study may
      facilitate further translational medicine research into the prevention and
      treatment of colorectal cancer liver metastasis. 

PMID- 25760248
TI  - Acute Onset of Acrokeratosis Paraneoplastica (Bazex Syndrome).

PMID- 25760249
TI  - Re: is robot-assisted radical prostatectomy safe in men with high-risk prostate
      cancer? Assessment of perioperative outcomes, positive surgical margins, and use
      of additional cancer treatments.

PMID- 25760250
TI  - Re: activity and safety of ODM-201 in patients with progressive metastatic
      castration-resistant prostate cancer (ARADES): an open-label phase 1 dose
      escalation and randomised phase 2 dose expansion trial.

PMID- 25760251
TI  - Re: 5-year longitudinal follow-up after retropubic and transobturator midurethral
      slings.

PMID- 25760252
TI  - Re: AR-V7 and resistance to enzalutamide and abiraterone in prostate cancer.

PMID- 25760253
TI  - Re: whole-genome and whole-exome sequencing of bladder cancer identifies frequent
      alterations in genes involved in sister chromatid cohesion and segregation.

PMID- 25760254
TI  - Re: bacillus Calmette-guerin strain differences have an impact on clinical
      outcome in bladder cancer immunotherapy.

PMID- 25760256
TI  - High-dose insulin inhibits gap junction intercellular communication in vascular
      smooth muscle cells.
AB  - Gap junction intercellular communication (GJIC) is important in mediating
      intercellular substance and signal transmission. Connexin (Cx)43 is a major
      component involved in GJIC in vascular tissue and its abnormal expression is
      closely associated with various vascular diseases. Insulin resistance is the
      central component of metabolic syndrome, and high doses of insulin can affect
      vascular function through multiple pathways, resulting in cardiovascular disease.
      However, the effects of insulin on GJIC function and connexin (Cx)43 expression
      in vascular smooth muscle cells (VSMCs) remain unclear. Following treatment of
      VSMCs with different doses of insulin, a fluorescence recovery after
      photobleaching (FRAP) assay was performed to evaluate GJIC function in treated
      VSMCs. The results showed that high-dose insulin suppressed GJIC function.
      Western blot assays further demonstrated that high-dose insulin induced the
      phosphorylation of Cx43 at s368 and downregulated the expression of Cx43. H2O2
      release assays demonstrated that high-dose insulin treatment significantly
      elevated the cellular H2O2 level. In addition, compared with cells treated with
      high-dose insulin, pretreatment with catalase significantly restored the cellular
      GJIC function, decreased the phosphorylation level of Cx43 at s368, and enhanced
      Cx43 expression. In conclusion, these data indicate that high-dose insulin
      inhibits cellular GJIC function through the oxidative stress-activated signaling
      pathway. This phenomenon may also constitute a potential mechanism underlying the
      pathogenesis of insulin resistance and its complications. 

PMID- 25760257
TI  - [Contact endoscopy of the vocal folds in combination with narrow band imaging
      (compact endoscopy].

PMID- 25760258
TI  - [Tips & tricks: dynamic frequency analysis of otolith function using vestibular
      evoked myogenic potentials (VEMP)].

PMID- 25760259
TI  - [Questions for the specialist examination. Discussion of acute, unilateral
      vestibular failure; discussion of indications and contraindications for allergen
      specific immunotherapy].

PMID- 25760260
TI  - Bone biology & pathology moves on: from bone resorption to formation, the rise of
      new therapeutic opportunities and experimental tools.

PMID- 25760261
TI  - Validating of the pre-clinical mouse model for metastatic breast cancer to the
      mandible.
AB  - Metastatic breast carcinoma has a great tendency to spread to the mandible. It is
      concomitantly associated with bone destruction, food intake disorder, and a
      poorer prognosis. Appropriate animal models need to be developed for a better
      understanding of the mechanisms underlying the metastatic process of breast
      cancer cells to mandible and to test the effects of potential lead compounds.
      Here, we assessed the metastasis model of intracardiac injection using luciferase
      transfected metastatic breast cancer cells (MDA-MB-231Luc+) by determining the
      incidences of metastasis, mCT images, and histopathological results. A high
      bioluminescence signal mainly detected mandibular lesions with less frequent
      distal femora and proximal tibiae lesions. Extensive mandibular bone destruction
      occurred in nude mice grafted with metastatic breast cancer cells. This type of
      animal model might be a useful tool in assessing therapeutic implications and the
      efficacy of anti-cancer drugs for osteolytic cancers. 

PMID- 25760262
TI  - Bone tissue response to plasma-nitrided titanium implant surfaces.
AB  - A current goal of dental implant research is the development of titanium (Ti)
      surfaces to improve osseointegration. Plasma nitriding treatments generate
      surfaces that favor osteoblast differentiation, a key event to the process of
      osteogenesis. Based on this, it is possible to hypothesize that plasma-nitrided
      Ti implants may positively impact osseointegration. Objective The aim of this
      study was to evaluate the in vivo bone response to Ti surfaces modified by plasma
      nitriding treatments. Material and Methods Surface treatments consisted of 20% N2
      and 80% H2, 450 degrees C and 1.5 mbar during 1 h for planar and 3 h for hollow
      cathode. Untreated surface was used as control. Ten implants of each surface were
      placed into rabbit tibiae and 6 weeks post-implantation they were harvested for
      histological and histomorphometric analyses. Results Bone formation was observed
      in contact with all implants without statistically significant differences among
      the evaluated surfaces in terms of bone-to-implant contact, bone area between
      threads, and bone area within the mirror area. Conclusion Our results indicate
      that plasma nitriding treatments generate Ti implants that induce similar bone
      response to the untreated ones. Thus, as these treatments improve the physico
      chemical properties of Ti without affecting its biocompatibility, they could be
      combined with modifications that favor bone formation in order to develop new
      implant surfaces. 

PMID- 25760263
TI  - TiF4 and NaF varnishes as anti-erosive agents on enamel and dentin erosion
      progression in vitro.
AB  - OBJECTIVE: This study assessed the effect of fluoride varnishes on the
      progression of tooth erosion in vitro. MATERIAL AND METHODS: Forty-eight enamel
      and 60 root dentin samples were previously demineralized (0.1% citric acid, pH
      2.5, 30 min), leading to a baseline and erosive wear of 12.9 and 11.4 um,
      respectively. The samples were randomly treated (6 h) with a 4% TiF4 varnish
      (2.45%F-, pH 1.0), a 5.42% NaF varnish (2.45%F-, pH 5.0), a placebo varnish and
      no varnish (control). The samples were then subjected to erosive pH cycles (4x90
      s/day in 0.1% citric acid, intercalated with artificial saliva) for 5 days. The
      increment of the erosive tooth wear was calculated. In the case of dentin, this
      final measurement was done with and without the demineralized organic matrix
      (DOM). Enamel and dentin data were analyzed using ANOVA/Tukey's and Kruskal
      Wallis/Dunn tests, respectively (p<0.05). RESULTS: The TiF4 (mean+/-s.d: 1.5+/
      1.1 um) and NaF (2.1+/-1.7 um) varnishes significantly reduced enamel wear
      progression compared to the placebo varnish (3.9+/-1.1 um) and control (4.5+/-0.9
      um). The same differences were found for dentin in the presence and absence of
      the DOM, respectively: TiF4 (average: 0.97/1.87 um), NaF (1.03/2.13 um), placebo
      varnish (3.53/4.47 um) and control (3.53/4.36 um). CONCLUSION: The TiF4 and NaF
      varnishes were equally effective in reducing the progression of tooth erosion in
      vitro.

PMID- 25760264
TI  - New methodology for evaluating osteoclastic activity induced by orthodontic load.
AB  - Orthodontic tooth movement (OTM) is a dynamic process of bone modeling involving
      osteoclast-driven resorption on the compression side. Consequently, to estimate
      the influence of various situations on tooth movement, experimental studies need
      to analyze this cell. Objectives The aim of this study was to test and validate a
      new method for evaluating osteoclastic activity stimulated by mechanical loading
      based on the fractal analysis of the periodontal ligament (PDL)-bone interface.
      Material and Methods The mandibular right first molars of 14 rabbits were tipped
      mesially by a coil spring exerting a constant force of 85 cN. To evaluate the
      actual influence of osteoclasts on fractal dimension of bone surface, alendronate
      (3 mg/Kg) was injected weekly in seven of those rabbits. After 21 days, the
      animals were killed and their jaws were processed for histological evaluation.
      Osteoclast counts and fractal analysis (by the box counting method) of the PDL
      bone interface were performed in histological sections of the right and left
      sides of the mandible. Results An increase in the number of osteoclasts and in
      fractal dimension after OTM only happened when alendronate was not administered.
      Strong correlation was found between the number of osteoclasts and fractal
      dimension. Conclusions Our results suggest that osteoclastic activity leads to an
      increase in bone surface irregularity, which can be quantified by its fractal
      dimension. This makes fractal analysis by the box counting method a potential
      tool for the assessment of osteoclastic activity on bone surfaces in microscopic
      examination. 

PMID- 25760265
TI  - Osteopontin expression in reactive lesions of gingiva.
AB  - Reactive proliferations of the gingiva comprise lesions such as pyogenic
      granuloma (PG), inflammatory fibroepithelial hyperplasia (IFH), peripheral
      ossifying fibroma (POF), and peripheral giant cell lesion. Osteopontin (OPN) has
      a dual role, it promotes mineralization when it is bound to solid substrate, and
      on the other hand, it inhibits mineralization when it is seen in association with
      solution. Objectives The study aimed to evaluate the expression of osteopontin in
      normal gingival tissue and different types of focal reactive proliferations of
      gingival tissue, and its role in the development of calcification within it.
      Material and Methods The presence and distribution of osteopontin was assessed
      using immunohistochemistry in five cases of normal gingival tissue and 30 cases
      of focal reactive proliferations of gingiva. Results There was no expression of
      osteopontin in normal subjects. Few cases of pyogenic granuloma, inflammatory
      fibroepithelial hyperplasia, and all the cases of peripheral ossifying fibroma
      showed positivity for osteopontin in the inflammatory cells, stromal cells,
      extracellular matrix, and in the calcifications. Conclusion The expression of
      osteopontin in all the cases of peripheral ossifying fibroma speculates that the
      majority of the cases of peripheral ossifying fibroma originate from the
      periodontal ligament cells. The treatment modalities for peripheral ossifying
      fibroma should differ from other focal reactive proliferations of gingiva. 

PMID- 25760266
TI  - Effect of sumac extract on serum oxidative status, RANKL/OPG system and alveolar
      bone loss in experimental periodontitis in rats.
AB  - OBJECTIVES: Sumac (Rhus coriaria L.) is widely used spice which has several
      properties such as antioxidant, anti-inflammatory and antimicrobial. The purpose
      of this animal study was to evaluate the effects of sumac extract on levels of
      receptor activator of nuclear factor-kappa B ligand (RANKL), osteoprotegerin
      (OPG) expression, serum oxidative status, and alveolar bone loss in experimental
      periodontitis. MATERIAL AND METHODS: Twenty-four Wistar rats were separated into
      three groups: non-ligated (NL, n=8), ligature only (LO, n=8), and ligature and
      treated with sumac extract (S, n=8) (20 mg/kg per day for 11 days). A 4/0 silk
      suture was placed around the mandibular right first molars subgingivally; after
      11 days, the rats were sacrificed, and alveolar bone loss was histometrically
      measured. The detection of RANKL and OPG were immunohistochemically performed.
      Levels of serum total antioxidant status (TAS)/total oxidant status (TOS), and
      oxidative stress index (OSI) were also analyzed. RESULTS: Alveolar bone loss was
      significantly greater in the LO group compared to the S and NL groups (p<0.05).
      The number of inflammatory cell infiltrate (ICI) and osteoclasts in the LO group
      was significantly higher than that of the NL and S groups (p<0.05). The number of
      osteoblasts in the LO and S groups was significantly higher than that of the NL
      group (p<0.05). There were significantly more RANKL-positive cells in the LO
      group than in the S and NL groups (p<0.05). OPG-positive cells were higher in S
      group than in LO and NL groups (p<0.05). TOS and OSI levels were significantly
      reduced in S group compared to LO group (P<0.05) and TAS levels were similar in S
      and NL group (p>0.05). CONCLUSIONS: The present study showed that systemic
      administration of sumac extract may reduce alveolar bone loss by affecting
      RANKL/OPG balance, TOS and OSI levels in periodontal disease in rats.

PMID- 25760267
TI  - Novel biological activity of ameloblastin in enamel matrix derivative.
AB  - OBJECTIVE: Enamel matrix derivative (EMD) is used clinically to promote
      periodontal tissue regeneration. However, the effects of EMD on gingival
      epithelial cells during regeneration of periodontal tissues are unclear. In this
      in vitro study, we purified ameloblastin from EMD and investigated its biological
      effects on epithelial cells. MATERIAL AND METHODS: Bioactive fractions were
      purified from EMD by reversed-phase high-performance liquid chromatography using
      hydrophobic support with a C18 column. The mouse gingival epithelial cell line GE
      1 and human oral squamous cell carcinoma line SCC-25 were treated with purified
      EMD fraction, and cell survival was assessed with a WST-1 assay. To identify the
      proteins in bioactive fractions of EMD, we used proteome analysis with two
      dimensional gel electrophoresis followed by identification with liquid
      chromatography-tandem mass spectrometry (LC-MS/MS) analysis. RESULTS: Purified
      fractions from EMD suppressed proliferation of GE-1 and SCC-25. LC-MS/MS revealed
      that ameloblastin in EMD is the component responsible for inhibiting epithelial
      cell proliferation. The inhibitory effect of ameloblastin on the proliferation of
      GE-1 and SCC-25 was confirmed using recombinant protein. CONCLUSION: The
      inhibitory effects of EMD on epithelial cell proliferation are caused by the
      biological activities of ameloblastin, which suggests that ameloblastin is
      involved in regulating epithelial downgrowth in periodontal tissues.

PMID- 25760268
TI  - Relationship between acetaldehyde concentration in mouth air and tongue coating
      volume.
AB  - OBJECTIVE: Acetaldehyde is the first metabolite of ethanol and is produced in the
      epithelium by mucosal ALDH, while higher levels are derived from microbial
      oxidation of ethanol by oral microflora such as Candida species. However, it is
      uncertain whether acetaldehyde concentration in human breath is related to oral
      condition or local production of acetaldehyde by oral microflora. The aim of this
      pilot study was to investigate the relationship between physiological
      acetaldehyde concentration and oral condition in healthy volunteers. MATERIAL AND
      METHODS: Sixty-five volunteers (51 males and 14 females, aged from 20 to 87 years
      old) participated in the present study. Acetaldehyde concentration in mouth air
      was measured using a portable monitor. Oral examination, detection of oral
      Candida species and assessment of alcohol sensitivity were performed. RESULTS:
      Acetaldehyde concentration [median (25%, 75%)] in mouth air was 170.7 (73.5,
      306.3) ppb. Acetaldehyde concentration in participants with a tongue coating
      status score of 3 was significantly higher than in those with a score of 1
      (p<0.017). After removing tongue coating, acetaldehyde concentration decreased
      significantly (p<0.05). Acetaldehyde concentration was not correlated with other
      clinical parameters, presence of Candida species, smoking status or alcohol
      sensitivity. CONCLUSION: Physiological acetaldehyde concentration in mouth air
      was associated with tongue coating volume.

PMID- 25760269
TI  - Effect of composite surface treatment and aging on the bond strength between a
      core build-up composite and a luting agent.
AB  - OBJECTIVE: The purpose of this study was to assess the influence of conditioning
      methods and thermocycling on the bond strength between composite core and resin
      cement. MATERIAL AND METHODS: Eighty blocks (8*8*4 mm) were prepared with core
      build-up composite. The cementation surface was roughened with 120-grit carbide
      paper and the blocks were thermocycled (5,000 cycles, between 5 degrees C and 55
      degrees C, with a 30 s dwell time in each bath). A layer of temporary luting
      agent was applied. After 24 h, the layer was removed, and the blocks were divided
      into five groups, according to surface treatment: (NT) No treatment (control);
      (SP) Grinding with 120-grit carbide paper; (AC) Etching with 37% phosphoric acid;
      (SC) Sandblasting with 30 mm SiO2 particles, silane application; (AO)
      Sandblasting with 50 mm Al2O3 particles, silane application. Two composite blocks
      were cemented to each other (n=8) and sectioned into sticks. Half of the
      specimens from each block were immediately tested for microtensile bond strength
      (uTBS), while the other half was subjected to storage for 6 months, thermocycling
      (12,000 cycles, between 5 degrees C and 55 degrees C, with a dwell time of 30 s
      in each bath) and uTBS test in a mechanical testing machine. Bond strength data
      were analyzed by repeated measures two-way ANOVA and Tukey test (alpha=0.05).
      RESULTS: The uTBS was significantly affected by surface treatment (p=0.007) and
      thermocycling (p=0.000). Before aging, the SP group presented higher bond
      strength when compared to NT and AC groups, whereas all the other groups were
      statistically similar. After aging, all the groups were statistically similar. SP
      submitted to thermocycling showed lower bond strength than SP without
      thermocycling. CONCLUSION: Core composites should be roughened with a diamond bur
      before the luting process. Thermocycling tends to reduce the bond strength
      between composite and resin cement.

PMID- 25760271
TI  - Numerical study of effect of elastomeric stress absorbers on stress reduction in
      bone-dental implant interface.
AB  - OBJECTIVE: This paper focused on optimal stress distribution in the mandibular
      bone surrounding a dental implant and is devoted to the development of a modified
      Osteoplant(r) implant type in order to minimize stress concentration in the bone
      implant interface. MATERIAL AND METHODS: This study investigated 0.4 mm thick
      layers of two elastomeric stress barriers incorporated into the dental implant
      using 3-D finite element analysis. RESULTS: Overall, this proposed implant
      provoked lower load transfer in bone-implant interface due to the effect of the
      elastomers as stress absorbers. The stress level in the bone was reduced between
      28% and 42% for three load cases: 75 N, 60 N and 27 N in corono-apical, linguo
      buccal and disto-mesial direction, respectively. CONCLUSION: The proposed model
      provided an acceptable solution for load transfer reduction to the mandible. This
      investigation also permitted to choose how to incorporate two elastomers into the
      Osteoplant(r) implant system.

PMID- 25760270
TI  - Differential expression of stem cell-like proteins in normal, hyperplastic and
      dysplastic oral epithelium.
AB  - OBJECTIVE: The identification of stem cells (SC) remains challenging. In the
      human oral mucosal epithelium, these cells are believed to be in the basal layer
      (stem cell niche), but their exact location is unclear. The aim of this study was
      to examine the dysplastic oral epithelium for these SC-like proteins in order to
      assess their diagnostic value as biomarkers complementing the histological
      grading of dysplasia. MATERIAL AND METHODS: Thirty oral epithelial dysplasia
      (OED), 25 oral lichen planus (OLP), 10 oral hyperkeratosis and 5 normal oral
      epithelium (OE) were immunohistochemically examined for four SC markers [integrin
      beta1, neuron-glial-2 (NG2), notch 1 (N1) and keratin 15 (K15)]. RESULTS: Three
      of four SC markers were heterogeneously detected in all samples. K15
      overexpression in the lower two-thirds of severe OED suggests an expanded SC
      niche. Integrin beta1 distribution pattern was not measurably different between
      OEDs and control. NG2 was almost negative to absent in all samples examined. N1
      expression was weak and highly variable in normal and dysplastic epithelium,
      making it an unreliable epithelial stem cell marker. CONCLUSIONS: Present
      findings suggest that these markers were unable to identify individual epithelial
      stem cells. Instead, subpopulations of cells, most probably stem cells and
      transit amplifying cells with stem cell-like properties were identified in the
      dysplastic oral epithelium. The characteristic expressions of K15 might be of
      diagnostic value for oral dysplasia and should be investigated further.

PMID- 25760272
TI  - A titration model for evaluating calcium hydroxide removal techniques.
AB  - OBJECTIVE: Calcium hydroxide (Ca(OH)2) has been used in endodontics as an
      intracanal medicament due to its antimicrobial effects and its ability to
      inactivate bacterial endotoxin. The inability to totally remove this intracanal
      medicament from the root canal system, however, may interfere with the setting of
      eugenol-based sealers or inhibit bonding of resin to dentin, thus presenting
      clinical challenges with endodontic treatment. This study used a chemical
      titration method to measure residual Ca(OH)2 left after different endodontic
      irrigation methods. MATERIAL AND METHODS: Eighty-six human canine roots were
      prepared for obturation. Thirty teeth were filled with known but different
      amounts of Ca(OH)2 for 7 days, which were dissolved out and titrated to
      quantitate the residual Ca(OH)2 recovered from each root to produce a standard
      curve. Forty-eight of the remaining teeth were filled with equal amounts of
      Ca(OH)2 followed by gross Ca(OH)2 removal using hand files and randomized
      treatment of either: 1) Syringe irrigation; 2) Syringe irrigation with use of an
      apical file; 3) Syringe irrigation with added 30 s of passive ultrasonic
      irrigation (PUI), or 4) Syringe irrigation with apical file and PUI (n=12/group).
      Residual Ca(OH)2 was dissolved with glycerin and titrated to measure residual
      Ca(OH)2 left in the root. RESULTS: No method completely removed all residual
      Ca(OH)2. The addition of 30 s PUI with or without apical file use removed Ca(OH)2
      significantly better than irrigation alone. CONCLUSIONS: This technique allowed
      quantification of residual Ca(OH)2. The use of PUI (with or without apical file)
      resulted in significantly lower Ca(OH)2 residue compared to irrigation alone.

PMID- 25760273
TI  - Management of the Class III malocclusion treated with maxillary expansion,
      facemask therapy and corrective orthodontic. A 15-year follow-up.
AB  - The facial growth of Class III malocclusion worsens with age, in this case, the
      early orthopedic treatment, providing facial balance, modifying the maxillofacial
      growth and development. A 7.6-year old boy presented with Class III malocclusion
      associated with anterior crossbite; the mandible was shifted to the right and the
      maxilla had a transversal deficiency. Rapid maxillary expansion followed by
      facemask therapy was performed, to correct the anteroposterior relationship and
      improve the facial profile. The patient was followed for a 15-year period, after
      completion of the treatment, and stability was observed. Growing patients should
      be monitored following their treatment, so as to prevent malocclusion relapse. 

PMID- 25760274
TI  - Second harmonic generation on self-assembled tilted gold nanowires.
AB  - Here we present measurements on a metasurface composed by tilted gold nanowires.
      The metasurface can induce an optical chiral response of the whole sample when
      the light impinges on the sample out of the normal incidence angle. In order to
      investigate the symmetry breaking induced by the geometry, we measured the second
      harmonic generation (SHG) signal generated by circular polarized pulsed light.
      This technique has demonstrated to be a powerful method in order to investigate
      the chiral morphology of nanostructures. 

PMID- 25760276
TI  - Hydration structure and mobility of the water contained in poly(ethylene
      terephthalate).
AB  - We have studied the state of the water contained in poly(ethylene terephthalate)
      (PET), which consists of repeat units of OCC6H4COOCH2CH2O, in variously hydrated
      states. We first determined the hydration structure of the water therein not only
      from its OH stretching spectrum in a thinner sample but also from the hydration
      energy, the effect of the hydrogen bonding on the lengths of the donor and
      acceptor bonds, and the OH stretching frequencies of the water for the optimized
      1:1 hydrate structures (quantum-chemically calculated). It has been found that
      the water bridges two ester C?O's in the manner of C?O...H-O-H...O?C therein and
      that about a 0.05 mole fraction of the C?O groups is bridged by the water in a
      PET sample hydrated in open air. We then carefully analyzed the state of the
      hydrating water in a thicker sample from its combination band around 5240 cm(-1),
      which significantly changes in frequency and bandwidth depending on the quantity
      of the contained water. It has been shown that the hydrating water molecules are
      so mobile as to begin to intermolecularly interact among themselves at a low
      hydration density of 10-15 water molecules per 1000 repeat units of
      OCC6H4COOCH2CH2O in the solid matrix. 

PMID- 25760277
TI  - Comparison of 2 Different Exercise Approaches: Tai Chi Versus Otago, in Community
      Dwelling Older Women.
AB  - BACKGROUND AND PURPOSE: Regular exercise can delay age-related risk factors and
      can maintain or improve physical health and activity in older adults leading to a
      decrease in fall risk. The purpose of this study was to compare 2 different
      interventions for fall prevention, tai chi (TC) and Otago, by examining lower
      extremity strength, balance, and spatiotemporal gait parameters in community
      dwelling older women. METHODS: We performed a randomized trial in which subjects
      were assigned to 1 of 2 groups: the TC group (n = 21; age, 72.8 +/- 4.7 years,
      range: 65-83 years), which participated in a modified Sun-style TC exercise
      program; and the Otago group (n = 24; age, 71.5 +/- 3.6 years, range: 65-79
      years), which participated in the Otago exercise program. The Timed Up and Go
      (TUG) test, functional reach (FR) test, one-leg standing (OLS) test, 5 times sit
      to-stand test (5*STS), 30-second sit-to-stand (30s STS) test, and gait parameters
      (gait velocity, step length, step width, stride time, and cadence) were measured
      before and after the intervention. RESULTS: Both groups showed statistically
      significant improvements in balance (TUG and OLS tests), lower extremity strength
      (5*STS and 30s STS tests), and spatiotemporal gait parameters, except for step
      width and step length (P < .05). The Otago group showed a significantly improved
      FR, whereas the TC group showed a significantly improved step length after the
      intervention (P < .05). Furthermore, the Otago group exhibited greater
      improvements in the TUG (P < .001), FR (P < .001), 5*CST (P < .01), and 30-second
      CST (P < .01) tests: a faster cadence (P < .001) and shorter stride time (P <
      .001) when compared with the TC group. The TC group showed greater improvements
      in the OLS test, step length, and step width (P < .01) and faster gait velocity
      (P < .05) than the Otago group. DISCUSSION AND CONCLUSIONS: The findings from
      this study support the efficacy of the TC and Otago exercise programs in
      improving mobility in this sample of subjects. Furthermore, the Otago group
      showed greater improvement in lower extremity strength, whereas the TC group
      showed greater improvement in balance (OLS test). Also, the TC group showed a
      greater improvement in gait velocity after TC training program compared with the
      Otago exercise program. However, this study does not elucidate which exercise
      program is a more effective intervention method with older women for fall
      prevention.

PMID- 25760275
TI  - Clostridium difficile drug pipeline: challenges in discovery and development of
      new agents.
AB  - In the past decade Clostridium difficile has become a bacterial pathogen of
      global significance. Epidemic strains have spread throughout hospitals, while
      community acquired infections and other sources ensure a constant inoculation of
      spores into hospitals. In response to the increasing medical burden, a new C.
      difficile antibiotic, fidaxomicin, was approved in 2011 for the treatment of C.
      difficile-associated diarrhea. Rudimentary fecal transplants are also being
      trialed as effective treatments. Despite these advances, therapies that are more
      effective against C. difficile spores and less damaging to the resident
      gastrointestinal microbiome and that reduce recurrent disease are still
      desperately needed. However, bringing a new treatment for C. difficile infection
      to market involves particular challenges. This review covers the current drug
      discovery pipeline, including both small molecule and biologic therapies, and
      highlights the challenges associated with in vitro and in vivo models of C.
      difficile infection for drug screening and lead optimization. 

PMID- 25760278
TI  - Postaerobic Exercise Blood Pressure Reduction in Very Old Persons With
      Hypertension.
AB  - BACKGROUND AND PURPOSE: A single bout of aerobic exercise acutely decreases blood
      pressure, even in older adults with hypertension. Nonetheless, blood pressure
      responses to aerobic exercise in very old adults with hypertension have not yet
      been documented. Therefore, this study aimed to assess the effect of a single
      session of aerobic exercise on postexercise blood pressure in very old adults
      with hypertension. METHODS: Eighteen older adults with essential hypertension
      were randomized into exercise (N = 9, age: 83.4 +/- 3.2 years old) or control (N
      = 9, age: 82.7 +/- 2.5 years old) groups. The exercise group performed a session
      of aerobic exercise constituting 2 periods of 10 minutes of walking at an
      intensity of 40% to 60% of the heart rate reserve. The control group rested for
      the same period of time. Anthropometric variables and medication status were
      evaluated at baseline. Heart rate and systolic and diastolic blood pressures were
      measured at baseline, after exercise, and at 20 and 40 minutes postexercise.
      RESULTS: Systolic blood pressure showed a significant interaction for group *
      time (F3,24 = 6.698; P = .002; etap(2) = 0.153). In the exercise group, the
      systolic blood pressure at 20 (127.3 +/- 20.9 mm Hg) and 40 minutes (123.7 +/-
      21.0 mm Hg) postexercise was significantly lower in comparison with baseline
      (135.6 +/- 20.6 mm Hg). Diastolic blood pressure did not change. Heart rate was
      significantly higher after the exercise session. In the control group, no
      significant differences were observed. CONCLUSIONS: A single session of aerobic
      exercise acutely reduces blood pressure in very old adults with hypertension and
      may be considered an important nonpharmacological strategy to control
      hypertension in this age group.

PMID- 25760279
TI  - Fine-mapping the human leukocyte antigen locus in rheumatoid arthritis and other
      rheumatic diseases: identifying causal amino acid variants?
AB  - PURPOSE OF REVIEW: To provide an update on and the context of the recent findings
      obtained with novel statistical methods on the association of the human leukocyte
      antigen (HLA) locus with rheumatic diseases. RECENT FINDINGS: Novel single
      nucleotide polymorphism fine-mapping data obtained for the HLA locus have
      indicated the strongest association with amino acid positions 11 and 13 of HLA
      DRB1 molecule for several rheumatic diseases. On the basis of these data, a
      dominant role for position 11/13 in driving the association with these diseases
      is proposed and the identification of causal variants in the HLA region in
      relation to disease susceptibility implicated. SUMMARY: The HLA class II locus is
      the most important risk factor for several rheumatic diseases. Recently, new
      statistical approaches have identified previously unrecognized amino acid
      positions in the HLA-DR molecule that associate with anticitrullinated protein
      antibody-negative and anticitrullinated protein antibody-positive rheumatoid
      arthritis. Likewise, similar findings have been made for other rheumatic
      conditions such as giant-cell arteritis and systemic lupus erythematosus.
      Interestingly, all these studies point toward an association with the same amino
      acid positions: amino acid positions 11 and 13 of the HLA-DR beta chain. As both
      these positions influence peptide binding by HLA-DR and have been implicated in
      antigen presentation, the novel fine-mapping approach is proposed to map causal
      variants in the HLA region relevant to rheumatoid arthritis and several rheumatic
      diseases. If these interpretations are correct, they would direct the biological
      research aiming to address the explanation for the HLA-disease association. Here,
      we provide an overview of the recent findings and evidence from literature that,
      although relevant new insights have been obtained on HLA-disease associations,
      the interpretation of the biological role of these amino acids as causal variants
      explaining that such associations should be taken with caution.

PMID- 25760280
TI  - Update on autoantibodies to modified proteins.
AB  - PURPOSE OF REVIEW: This article provides an update on the recent findings on
      autoantibodies to modified proteins in rheumatoid arthritis (RA). RECENT
      FINDINGS: In the past few years, the knowledge on the autoantibodies to
      citrullinated antigens has expanded considerably. More specifically, it is now
      clear that many different citrullinated protein antigens present in the synovial
      compartment can be recognized by anticitrullinated protein antibody (ACPA). This
      is most likely a consequence of the cross-reactivity the ACPA response displays
      to citrullinated proteins. It is now also clear that the isotype usage and the
      citrullinated epitope repertoire recognized by ACPA expands before the
      manifestation of full-blown RA and that this goes hand in hand with a rise in
      ACPA level. Next to ACPA, several other autoantibody systems directed against
      other posttranslationally modified proteins, such as proteins containing a
      homocitrulline residue resulting from protein carbamylation, have been
      identified. On the whole, the evolution of these autoantibody systems in time
      mimics the evolution of the ACPA response, indicating that the break of tolerance
      underlying different autoimmune responses present in RA occurs before disease
      onset, with a further maturation of these responses shortly before or concurrent
      with the manifestation of clinical symptoms. SUMMARY: Since the discovery of
      rheumatoid factor over 65 years ago, our knowledge on autoantibodies and their
      relevance for rheumatic disease has expanded enormously. Especially, the
      realization that next to rheumatoid factor, also other autoantibodies recognizing
      posttranslationally modified proteins are present in RA patients has contributed
      significantly to the understanding of disease. In the past few years, several new
      autoantibody systems to differentially modified proteins have been identified and
      their relation to clinical outcome has been scrutinized. Here, we provide an
      update on the recent developments in our knowledge on the presence and
      consequences of autoantibodies to modified proteins in RA.

PMID- 25760281
TI  - Current approaches to osteoporosis treatment.
AB  - PURPOSE OF REVIEW: Osteoporosis is a skeletal disorder in which bone strength is
      decreased leading to an increased risk of fracture. In line with advances in
      knowledge of bone biology, the past several years have held major therapeutic
      advances in osteoporosis treatment. In this article, we review the current
      approaches to osteoporosis treatment with a focus on issues of interest to the
      practicing rheumatologist. RECENT FINDINGS: In addition to the bisphosphonates,
      the introduction of denosumab, teriparatide and selective oestrogen-receptor
      modulators, as well as the development of new therapeutic agents (romosozumab and
      odanacatib) has opened the door to new approaches, including individualization of
      treatment in different clinical circumstances based on patient comorbidities and
      preference; combination therapy to optimize treatment effect; and consideration
      of goal-based treatment. Postmarketing surveillance of bisphosphonates has
      revealed several safety concerns including osteonecrosis of the jaw and atypical
      femoral fractures. Bisphosphonate drug holidays should be considered in patients
      on bisphosphonate therapy because prolonged treatment may be associated with
      adverse events. SUMMARY: Substantial progress has been made in the past several
      years in the understanding and modification of osteoporosis management. Many
      conditions encountered by rheumatologists are associated with bone loss;
      therefore, the rheumatologist needs to be aware of the current approaches in
      osteoporosis management.

PMID- 25760282
TI  - Pipe dreams: concealed methamphetamine causing severe toxicity.

PMID- 25760283
TI  - Relationship of tidal volume to peak flow, breath rate, I: E and plateau time:
      mock study.
AB  - BACKGROUND: The purpose of this study was to determine the functional
      relationship between tidal volume (VT) and 4 other ventilator parameters.
      METHODS: The following parameters were collected from an AVEA ventilator
      operating in the volume-controlled ventilation mode: VT (in L), peak flow (Vmax,
      in L/min), breath rate (f, in bpm), inspiratory-to-expiratory time ratio (I:E)
      and plateau time (TP, in s). The relationship between VT and each of the other
      variables was determined. RESULTS: When the other parameters were held constant,
      VT was positively correlated with Vmax and I:E, but negatively correlated with f
      and TP. When the velocity versus time curve was a 50% linearly decreasing wave,
      the functional relationship among the 5 parameters was governed by the equation:
      VT = 180 Vmax (60f - 60f [1 + I:E] - TP). CONCLUSIONS: The functional
      relationship among the 5 parameters for the AVEA ventilator in the volume
      controlled ventilation mode was determined. The parameters should be controlled
      in accordance with the patient's pathophysiological needs.

PMID- 25760284
TI  - The role of p21-activated kinases in pancreatic cancer.
AB  - Pancreatic cancer is an aggressive cancer with a poor prognosis and an overall 5
      year survival rate of less than 5%. Management has not improved significantly
      over the last 30 years, and a better understanding of the genetic and molecular
      changes that occur is urgently required. Many of these changes appear to involve
      the p21-activated kinases (PAKs). The PAK family consists of 6 isoforms, 2 of
      which, PAK1 and PAK4, are up-regulated and/or hyperactivated in pancreatic
      cancer. p21-Activated kinases can mediate many different cellular processes
      especially those contributing to cancer development and progression. These
      processes include the regulation of cytoskeletal dynamics and cell adhesion, the
      evasion of apoptosis, and the promotion of cell survival, proliferation,
      migration, and invasion. p21-Activated kinases may also be involved in
      characteristics unique to pancreatic tumors, such as interplay with the
      pancreatic stroma, the re-emergence of embryonic pathways, and the involvement of
      a subset of microRNAs and heat shock proteins. This review highlights the
      potential role of PAKs in pancreatic cancer and provides a foundation for more
      effective therapeutics to improve our current treatment of pancreatic cancer. 

PMID- 25760285
TI  - Familial adenomatous polyposis and pancreatic cancer.

PMID- 25760286
TI  - Preparation of catalytic films of the Au nanoparticle-carbon composite tubular
      arrays.
AB  - Catalytic films comprising the arrayed mesoporous and big-inner-diameter carbon
      nanotubes embedded with high density Au nanoparticles were prepared through a
      template-directed carbonization route. 

PMID- 25760289
TI  - Hidradenitis suppurativa and metabolic syndrome: a comparative cross-sectional
      study of 3207 patients.
AB  - BACKGROUND: Hidradenitis suppurativa (HS) is a chronic relapsing inflammatory
      skin disease. OBJECTIVES: To evaluate the association between HS and metabolic
      syndrome and its component morbidities in a large, community-based cohort of
      patients with HS, using the database of Clalit Health Services, the largest
      public healthcare provider in Israel. METHODS: A cross-sectional study was
      performed. Metabolic syndrome was defined as the presence of at least three of
      the following conditions: diabetes, hyperlipidaemia, hypertension and obesity.
      The association between HS and metabolic syndrome was assessed by a multivariate
      logistic regression model, adjusting for age, sex, diabetes, hypertension,
      hyperlipidaemia, obesity and smoking status. RESULTS: The study included 3207
      patients with HS (general frequency of 0.07%) diagnosed by a dermatologist in
      primary-care centres, and 6412 age- and sex-matched control patients without HS.
      HS was significantly associated with metabolic syndrome [odds ratio (OR) 1.61,
      95% confidence interval (CI) 1.36-1.89], diabetes (OR 1.41, 95% CI 1.19-1.66),
      obesity (OR 1.71, 95% CI 1.53-1.91), hyperlipidaemia (OR 1.14, 95% CI 1.02-1.28)
      and hypertension (OR 1.19, 95% CI 1.03-1.38). CONCLUSIONS: We found an
      association between HS and diabetes, hyperlipidaemia, obesity, hypertension and
      metabolic syndrome among a large community-based cohort of patients with HS.
      Clinicians should take into account that patients with HS may have one or more
      undiagnosed components of metabolic syndrome despite their young age. Thus,
      appropriate targeted screening is advised.

PMID- 25760291
TI  - Fluorescence spectroscopy in process analytical technology (PAT): simultaneous
      quantification of two active pharmaceutical ingredients in a tablet formulation.
AB  - Many pharmaceuticals include highly potent active pharmaceutical ingredients
      (API), which only require a small dosage to obtain the desired therapeutic
      effect. This leads to a challenge for quantification of the API using process
      analytical technology, since the standard nondestructive measurement technique,
      near-infrared spectroscopy, is not able to quantify below 1% (weight/weight
      (w/w)) API content. In formulations with more than one API, this challenge is
      further increased. The purpose of this study is to scrutinize the potential of
      fluorescence spectroscopy for the simultaneous quantification of two APIs:
      flupentixol (FLU) in low dosage (0.208-0.625% w/w free base) and melitracen (MEL)
      (4.17-12.5% w/w free base) in a tablet formulation. Despite internal quenching
      between the ingredients and the two APIs, this paper demonstrates that it is
      possible to establish calibrations using partial least squares (PLS) regression
      on unfolded fluorescence landscapes with a root mean square error of prediction
      and relative error of 0.038% (w/w) and 9.1%, for FLU and 0.344% (w/w) and 4.1%
      for MEL, respectively. 

PMID- 25760292
TI  - Determination of copper and zinc pollutants in Ludwigia prostrata Roxb using near
      infrared reflectance spectroscopy (NIRS).
AB  - The feasibility of using near-infrared reflectance spectroscopy (NIRS) to
      determine the concentrations of copper (Cu) and zinc (Zn) in Ludwigia prostrata
      Roxb plants was investigated. Ludwigia prostrata Roxb plants were grown over a
      full growth cycle under controlled laboratory conditions in soils contaminated
      with heavy metals. The Cu and Zn concentrations in 72 L. prostrata Roxb samples
      were analyzed using flame atomic absorption spectrometry, and NIRS spectra were
      collected in the 1099-2500 nm range. Five mathematical treatments of the spectral
      data were compared prior to developing the calibration models (n = 48) using
      partial least squares regression methods. The two calibration models for Cu and
      Zn concentrations were evaluated according to the correlation coefficient of
      cross-validation (R(cv)) and root mean squares error of cross-validation. The
      highest R(cv) and the lowest RMSECV were obtained for Cu (0.9 and 7.24 mg kg(-1))
      and Zn (0.94 and 19.17 mg kg(-1)), respectively. The results showed that near
      infrared diffuse reflectance spectroscopy can be used for the rapid determination
      of Cu and Zn in leaves of L. prostrata Roxb plants.

PMID- 25760293
TI  - Screening, evaluation, and management of cancer-related fatigue: Ready for
      implementation to practice?
AB  - Answer questions and earn CME/CNE Evidence regarding cancer-related fatigue
      (fatigue) has accumulated sufficiently such that recommendations for screening,
      evaluation, and/or management have been released recently by 4 leading cancer
      organizations. These evidence-based fatigue recommendations are available for
      clinicians, and some have patient versions; but barriers at the patient,
      clinician, and system levels hinder dissemination and implementation into
      practice. The underlying biologic mechanisms for this debilitating symptom have
      not been elucidated completely, hindering the development of mechanistically
      driven interventions. However, significant progress has been made toward methods
      for screening and comprehensively evaluating fatigue and other common symptoms
      using reliable and valid self-report measures. Limited data exist to support the
      use of any pharmacologic agent; however, several nonpharmacologic interventions
      have been shown to be effective in reducing fatigue in adults. Never before have
      evidence-based recommendations for fatigue management been disseminated by 4
      premier cancer organizations (the National Comprehensive Cancer, the Oncology
      Nursing Society, the Canadian Partnership Against Cancer/Canadian Association of
      Psychosocial Oncology, and the American Society of Clinical Oncology). Clinicians
      may ask: Are we ready for implementation into practice? The reply: A variety of
      approaches to screening, evaluation, and management are ready for implementation.
      To reduce fatigue severity and distress and its impact on functioning,
      intensified collaborations and close partnerships between clinicians and
      researchers are needed, with an emphasis on system-wide efforts to disseminate
      and implement these evidence-based recommendations.

PMID- 25760294
TI  - Antiinflammatory and Wound Healing Effects of Caesalpinia sappan L.
AB  - Extracted compounds from Caesalpinia sappan L. were examined for the inhibitory
      activity against NO, PGE2 , and TNF-alpha productions and on associated
      transcription levels using RAW264.7 cells. They were also tested for their
      effects on wound healing using fibroblast L929 cells. Among the compounds tested,
      brazilin (8) was the most effective against lipopolysaccharide (LPS)-induced NO
      production in RAW264.7 cells with an IC50 value of 10.3 MUM, followed by
      sappanchalcone (2, 31.0 MUM). Brazilin (8) also inhibited PGE2 and TNF-alpha
      production with IC50 values of 12.6 and 87.2 MUM, respectively. The
      antiinflammatory mechanism of brazilin involved down regulation of the mRNA
      expressions of the iNOS, COX-2, and TNF-alpha genes in a dose-dependent manner.
      An ethanol (EtOH) extract of C. sappan significantly increased fibroblast
      proliferation, fibroblast migration, and collagen production, whereas brazilin
      (8) only stimulated fibroblast migration. In addition, the EtOH extract showed no
      acute toxicity in mice, and it was therefore safe to make use of its potent
      antiinflammatory and wound healing activities. Brazilin was mainly responsible
      for its antiinflammatory effect through its ability to inhibit the production of
      NO, PGE2 , and TNF-alpha. This study supports the traditional use of C. sappan
      for treatment of inflammatory-related diseases.

PMID- 25760295
TI  - Improving reptile ecological risk assessment: oral and dermal toxicity of
      pesticides to a common lizard species (Sceloporus occidentalis).
AB  - Reptiles have been understudied in ecotoxicology, which limits consideration in
      ecological risk assessments. The goals of the present study were 3-fold: to
      improve oral and dermal dosing methodologies for reptiles, to generate reptile
      toxicity data for pesticides, and to correlate reptile and avian toxicity. The
      authors first assessed the toxicity of different dosing vehicles: 100 MUL of
      water, propylene glycol, and acetone were not toxic. The authors then assessed
      the oral and dermal toxicity of 4 pesticides following the up-and-down procedure.
      Neither brodifacoum nor chlorothalonil caused mortality at doses <= 1750 MUg/g.
      Under the "neat pesticide" oral exposure, endosulfan (median lethal dose [LD50] =
      9.8 MUg/g) was more toxic than lambda-cyhalothrin (LD50 = 916.5 MUg/g). Neither
      chemical was toxic via dermal exposure. An acetone dosing vehicle increased
      lambda-cyhalothrin toxicity (oral LD50 = 9.8 MUg/g; dermal LD50 = 17.5 MUg/g),
      but not endosulfan. Finally, changes in dosing method and husbandry significantly
      increased dermal lambda-cyhalothrin LD50s, which highlights the importance of
      standardized methods. The authors combined data from the present study with other
      reptile LD50s to correlate with available avian data. When only definitive LD50s
      were used in the analysis, a strong correlation was found between avian and
      reptile toxicity. The results suggest it is possible to build predictive
      relationships between avian and reptile LD50s. More research is needed, however,
      to understand trends associated with chemical classes and modes of action.

PMID- 25760296
TI  - Towards a stratified targeted approach with biologic treatments in rheumatoid
      arthritis: role of synovial pathobiology.
AB  - Rheumatoid Arthritis (RA) is a chronic, inflammatory, autoimmune disease
      affecting diarthrodial joints and extra-articular tissues; in the absence of an
      effective treatment, it is characterized by persistent symmetrical and erosive
      synovitis which leads to structural joint damage and lifelong disability. Several
      autoantibodies have been associated with RA such as rheumatoid factor (RF) and
      anti-citrullinated protein antibodies (ACPA). B cells have been shown to play a
      crucial role in the pathogenesis of RA by producing autoantibodies and promoting
      synovial inflammation through antigen presentation, T cells activation and
      cytokines production [1]. Although biologic agents have notably improved disease
      outcome and patients' quality of life, currently around 30-40% of subjects do not
      respond to treatment and the mechanisms leading to resistance are still not known
      [2]. For this reason, new prognostic biomarkers and predictors of response are
      needed. We and others have postulated that the development of biomarkers for
      patients' stratification prior therapeutic intervention may be possible through a
      better understanding of the different histopathological patterns present both in
      early and established individual RA patient and the related underlying cellular
      and molecular mechanisms. To date, Tumor Necrosis Factor (TNF)-alpha has been
      shown to be one of the master elements of inflammation in RA; however, even
      though therapies aimed at blocking this key cytokine have emerged as a major tool
      in the treatment of RA, a large proportion of patients (approximately 30-40%) do
      not achieve a meaningful clinical response assessed by either the American
      College of Rheumatology (ACR) or the European League Against Rheumatism (EULAR)
      criteria. The same limitation can be applied to the use of rituximab, a chimeric
      monoclonal antibody directed against CD20, which is uniquely expressed by all B
      lymphocytes during the maturation process from late stage pro-B cells to memory
      cells. The clinical efficacy of rituximab has been proved by several clinical
      studies [3] but it is highly variable. Currently, NICE guidelines recommend
      rituximab in patients with inadequate response to a first-line biologic therapy,
      including at least one anti-TNFalpha agent independently of their pre-treatment
      chance to respond. In all cases, whether considering biologics used for several
      years in RA patients (anti-TNFalpha or rituximab) or relatively newer biologics
      in clinical use (i.e. tocilizumab, an anti-interleukin (IL) -6 receptor blocking
      monoclonal antibody or abatacept, a CTLA4 inhibitor fusion protein designed to
      target the T cell co-stimulatory signal mediated through the CD28-CD80/86
      pathway), no validated biomarkers predictive of clinical response currently
      exist. Consequently, to date a "trial-and-error" approach is used in the
      prescription of biologics in RA, which has the obvious disadvantage of
      potentially exposing patients to drugs that they may not respond, with potential
      unnecessary side-effects, delaying use of an effective treatment and causing a
      significant economic burden to society. Therefore, identifying pre-treatment
      predictors of response with a customized stratification approach would be of
      invaluable importance in RA, also in consideration of the large number of
      biologics in development targeting novel pathways currently being tested in
      clinical trials. In this manuscript, we review existing data and provide future
      perspectives with regard to the role of synovial histopathology as a potential
      prognostic biomarker for patient stratification in RA, in particular regarding
      the use of specific biologic therapies. 

PMID- 25760297
TI  - Biological therapies in osteoarthritis.
AB  - Given the paucity of effective therapies and the increasing prevalence of
      osteoarthritis (OA) with ageing and overweight populations, new therapies for
      this painful, life-impairing condition are desperately needed, for both symptom
      relief and structural modification. With a growing understanding that OA involves
      multiple tissue pathologies including inflammation, many more therapeutic targets
      have been identified. This review will provide a current overview on the role of
      biologics in OA, including anti-tumour necrosis factor agents, growth factors and
      interleukin-1 antagonists. 

PMID- 25760298
TI  - Finding a place for interleukin-1 inhibitors in the treatment of rheumatologic
      diseases.
AB  - Interleukin-1 inhibitors were tested in large arthritis trials with less than
      impressive results, despite having convincing disease expression data and pre
      clinical animal model supporting the potential pathogenic role of this cytokine
      in these settings. Despite disappointing beginnings, some IL-1 pathway blocking
      drugs are now beginning to find a place in the pharmacopoeia of rheumatologists.
      Drug developers utilised rapidly growing understanding of the molecular pathway
      and the genetic basis of key diseases to seek out conditions in which IL-1
      pathway activation was much more likely to have a pivotal role in disease
      pathogenesis compared to the major arthritides. This review details the crucial
      advances in understanding of the IL-1 pathway activation which enabled this
      progress, particularly the advent of inflammasome biology. The drug development
      of IL-1 biologics in rheumatological diseases makes a fascinating case study
      illustrating major changes in drug development strategy encompassing closer
      synergies between translational biology, underlying molecular pathophysiology of
      disease, and novel clinical development pathways of biologic therapeutics. 

PMID- 25760299
TI  - Interleukin-6 in rheumatoid arthritis - from the laboratory to the bedside.
AB  - Rheumatoid arthritis (RA) is a common and debilitating disease. Expanded
      therapeutic options, targeting pro-inflammatory cytokines such as tumour necrosis
      factor (TNF) and interleukin-6 (IL-6), have revolutionised RA treatment. To date,
      efficacy data shows superiority of IL-6 inhibition over placebo, conventional
      disease modifying anti-rheumatic drugs such as methotrexate, and TNF inhibition.
      Moreover, while demonstrating some key differences in the safety profile compared
      with TNF inhibition (e.g. hyperlipidemia and neutropenia), these safety concerns
      have not, at least to date, been found to cause clinically significant adverse
      outcomes. Other safety parameters, such as infection and malignancy rates have
      been found to be comparable between IL-6 and TNF inhibition. This review explores
      the biology and clinical applications of IL-6 inhibition in the management of RA.

PMID- 25760300
TI  - Rheumatology: a force for change in monoclonal antibodies.
AB  - Monoclonal antibodies have undergone a radical evolutionary journey over the last
      25 years, with advances in molecular biology, process development and drug
      formulation underpinning their rise to becoming one of the most efficacious and
      economically important class of drug today. The success of antibodies for the
      treatment of rheumatological conditions, such as rheumatoid arthritis in
      particular, has driven the biopharmaceutical industry to optimize all aspects of
      therapeutic antibody discovery and development, in order to provide further
      benefits for patients over and above marketed treatments, via increased clinical
      efficacy and patient convenience. Recent advances in many of the key aspects of
      antibody design that are driving this evolution, such as affinity optimization,
      effector function modulation, pharmacokinetic engineering, as well as
      developments in subcutaneous drug delivery, are reviewed here. 

PMID- 25760301
TI  - Rheumatoid arthritis: an evolutionary force in biologics.
AB  - The advent of biologic therapy has transformed the outcomes of patients with
      Rheumatoid Arthritis (RA), but has also highlighted important issues for their
      development. Early attempts at T-cell driven therapies gave mixed results with
      difficulties extrapolating from non-human models to first in man trials. There is
      currently one T-cell modulating therapy - abatacept - licenced for use in RA.
      Cytokine inhibition has proven to be more fruitful with a number of anti-TNF and
      IL6 agents either licenced for use in RA or in development. The B-cell depleting
      therapy rituximab has also shown good efficacy as a chemotherapy agent repurposed
      for RA treatment. Overall the biologics show good efficacy in RA and have been
      shown to retard progression of radiographic joint damage. However, this benefit
      comes with a burden of increased infection risk and a financial cost
      significantly higher than conventional disease modifying therapies. As a result
      current UK licencing holds the biologics in reserve following failure of a
      conventional therapy and the presence of moderate to severely active disease. The
      long term use of the biologics in RA has highlighted the risk of immunogenicity,
      with significant proportions of patients developing anti-drug antibodies and
      losing therapeutic effect. The side effect profile and cost also raise the
      question around duration of therapy and trials of drug tapering following disease
      remission are now taking place with several biologic agents. Our inability to
      stratify patients to the most appropriate biologic drug (stratified or precision
      medicine) has also catalysed a large and critically important research agenda.
      Beyond identifying new biologic targets, the development of biosimilar agents
      will likely drive the future shape of the RA biologics market as lower cost
      alternatives are developed, thereby improving access to these therapies. 

PMID- 25760302
TI  - Suppression of problematic compound oligomerization by cosolubilization of
      nondetergent sulfobetaines.
AB  - Numerous small organic compounds exist in equilibrium among monomers, soluble
      oligomers, and insoluble aggregates in aqueous solution. Compound aggregation is
      a major reason for false positives in drug screening, and even soluble oligomers
      can interfere with structural and biochemical analyses. However, an efficient way
      to manage the equilibrium of aggregation-prone compounds, especially those
      involved with soluble oligomers, has not been established. In this study,
      solution NMR spectroscopy was used as a suitable technique to detect compound
      oligomers in equilibrium, and it was demonstrated that cosolubilization of
      nondetergent sulfobetaines (NDSBs) can largely suppress compound oligomerization
      and aggregation by shifting the equilibrium toward the monomers. The rotational
      correlation time was obtained from the ratio of the selective and nonselective
      longitudinal NMR relaxation times, which directly and quantitatively reflected
      the apparent sizes of the compounds in the equilibrium. The rotational
      correlation time of the aggregation-prone compound SKF86002 (1 mM) was
      substantially reduced from 0.31 to 0.23 ns by cosolubilization of 100 mM NDSB195.
      NDSB cosolubilization allowed us to perform successful structural and biochemical
      experiments with substantially fewer artifacts, which represents a strategy to
      directly resolve the problematic oligomerization and aggregation of compounds.

PMID- 25760304
TI  - Beneficial effects of tripterygium glycosides tablet on biomarkers in patients
      with ankylosing spondylitis.
AB  - The aim of the current study was to explore the effects and possible mechanisms
      of tripterygium glycosides tablet (TGT) in the treatment of active ankylosing
      spondylitis (AS). Thirty-six patients with active AS were given a 20 mg TGT
      treatment three times per day for 12 weeks, and 21 unrelated healthy controls
      were recruited as the control group. Efficacy measures included the Bath AS
      disease activity index (BASDAI), erythrocyte sedimentation rate (ESR) and C
      reactive protein (CRP) prior and subsequent to TGT treatment. Serum dickkopf
      homolog 1 (DKK1) and interleukin-17 (IL-17) levels before and after TGT treatment
      were assessed using reverse transcription-quantitative polymerase chain reaction
      (RT-qPCR) and ELISA assay. The levels of several serum biomarkers were determined
      by ELISA, including receptor activator of nuclear factor kappa-B ligand (RANKL),
      osteoprotegerin (OPG), bone alkaline phosphatase (BAP), bone morphogenetic
      protein-2 (BMP-2), matrix metalloproteinase-3 (MMP-3), cross-linked telopeptide
      of type II collagen (CTX-II), vascular endothelial growth factor (VEGF), and
      prostaglandin E2 (PGE2). After 12 weeks of TGT treatment, the BASDAI score of the
      patients was significantly reduced (P<0.05), their levels of ESR and CRP were
      significantly reduced to a normal level (P<0.05, P<0.05), RT-PCR and ELISA showed
      a significant increase in the level of DKK1 expression (P<0.05) and a significant
      decreased IL-17 expression (P<0.05), there was a significant increase in the
      expression of OPG, BAP and BMP-2 (P<0.01, P<0.01, P<0.01) and a significant
      reduction in the expression levels of RANKL, CTX-II. MMP-3, PGE2, and VEGF
      (P<0.01, P<0.01, P<0.01, P<0.05, P<0.01) compared with those of the controls. TGT
      is effective at improving the signs and symptoms of patients with AS through the
      regulation of serum biomarkers, and the mechanisms may be associated with the
      anti-inflammatory effect, inhibition of new bone formation and potential bone
      protective effects.

PMID- 25760303
TI  - Cannabis-related episodic memory deficits and hippocampal morphological
      differences in healthy individuals and schizophrenia subjects.
AB  - Cannabis use has been associated with episodic memory (EM) impairments and
      abnormal hippocampus morphology among both healthy individuals and schizophrenia
      subjects. Considering the hippocampus' role in EM, research is needed to evaluate
      the relationship between cannabis-related hippocampal morphology and EM among
      healthy and clinical groups. We examined differences in hippocampus morphology
      between control and schizophrenia subjects with and without a past (not current)
      cannabis use disorder (CUD). Subjects group-matched on demographics included 44
      healthy controls (CON), 10 subjects with a CUD history (CON-CUD), 28
      schizophrenia subjects with no history of substance use disorders (SCZ), and 15
      schizophrenia subjects with a CUD history (SCZ-CUD). Large-deformation, high
      dimensional brain mapping with MRI produced surface-based representations of the
      hippocampus that were compared across all four groups and correlated with EM and
      CUD history. Surface maps of the hippocampus were generated to visualize
      morphological differences. CON-CUD and SCZ-CUD were characterized by distinct
      cannabis-related hippocampal shape differences and parametric deficits in EM
      performance. Shape differences observed in CON-CUD were associated with poorer EM
      performance, while shape differences observed in SCZ-CUD were associated with a
      longer duration of CUD and shorter duration of CUD remission. A past history of
      CUD may be associated with notable differences in hippocampal morphology and EM
      impairments among adults with and without schizophrenia. Although the results may
      be compatible with a causal hypothesis, we must consider that the observed
      cannabis-related shape differences in the hippocampus could also be explained as
      biomarkers of a neurobiological susceptibility to poor memory or the effects of
      cannabis.

PMID- 25760305
TI  - Microfluidic selective concentration of microdroplet contents by spontaneous
      emulsification.
AB  - The selective concentration of the contents in a microdroplet using spontaneous
      emulsification was proposed and demonstrated in a microfluidic channel. Aqueous
      microdroplets having a 40-MUm diameter, in octane containing 100 mM of Span 80,
      shrank to 10 MUm within 10 min with nanodroplet formation at the interface of the
      microdroplets. The microdroplets' contents either stayed in the microdroplet or
      partitioned into the nanodroplets, depending on their properties. The size and
      the hydrophobicity of the contents are two parameters that determine
      concentration/separation. In addition, this method was applied to a bound complex
      and free ligand (B/F) separation to demonstrate its applicability to biochemical
      analyses. Here we report the separation of water-soluble molecules in
      microdroplets for the first time. This method is expected to enhance the
      flexibility of the design of droplet analytical processes and widen their
      applicability. 

PMID- 25760306
TI  - Solution-Processed Large-Area Nanocrystal Arrays of Metal-Organic Frameworks as
      Wearable, Ultrasensitive, Electronic Skin for Health Monitoring.
AB  - Pressure sensors based on solution-processed metal-organic frameworks nanowire
      arrays are fabricated with very low cost, flexibility, high sensitivity, and ease
      of integration into sensor arrays. Furthermore, the pressure sensors are suitable
      for monitoring and diagnosing biomedical signals such as radial artery pressure
      waveforms in real time. 

PMID- 25760307
TI  - Synthesis, electronic properties and WOLED devices of planar phosphorus
      containing polycyclic aromatic hydrocarbons.
AB  - We describe the synthesis and the physical properties of polyaromatic
      hydrocarbons (PAHs) containing a phosphorus atom at the edge. In particular, the
      impact of the successive addition of aromatic rings on the electronic properties
      was investigated by experimental (UV/Vis absorption, fluorescence, cyclic
      voltammetry) and theoretical studies (DFT). The physical properties recorded in
      solution and in the solid state showed that the P-containing PAHs exhibit
      properties expected for an emitter in white organic light-emitting diodes
      (WOLEDs). 

PMID- 25760309
TI  - Mechanism of bismuth telluride exfoliation in an ionic liquid solvent.
AB  - Bismuth telluride (Bi2Te3) is a well-known thermoelectric material that has a
      layered crystal structure. Exfoliating Bi2Te3 to produce two-dimensional (2D)
      nanosheets is extremely important because the exfoliated nanosheets possess
      unique properties, which can potentially revolutionize several material
      technologies such as thermoelectrics, heterogeneous catalysts, and infrared
      detectors. In this work, ionic liquid (IL) 1-butyl-3-methylimidazolium chloride
      ([C4mim]Cl) is used to exfoliate Bi2Te3 nanoplatelets. In both experiments and in
      molecular dynamics (MD) simulations, the Bi2Te3 nanoplatelets yield a stable
      dispersion of 2D nanosheets in the IL solvent, and our MD simulations provide
      molecular-level insight into the kinetics and thermodynamics of the exfoliation
      process. An analysis of the dynamics of Bi2Te3 during exfoliation indicates that
      the relative translation (sliding apart) of adjacent layers caused by IL-induced
      forces plays an important role in the process. Moreover, an evaluation of the MD
      trajectories and electrostatic interactions indicates that the [C4mim](+) cation
      is primarily responsible for initiating Bi2Te3 layer sliding and separation,
      while the Cl(-) anion is less active. Overall, our combined experimental and
      computational investigation highlights the effectiveness of IL-assisted
      exfoliation, and the underlying molecular-level insights should accelerate the
      development of future exfoliation techniques for producing 2D chalcogenide
      materials. 

PMID- 25760308
TI  - Clinicopathological significance of cytoplasmic transducer of ErbB2. 1 expression
      in gastric cancer.
AB  - The aim of the present study was to investigate the expression of transducer of
      ErbB2. 1 (TOB1) in gastric carcinoma and to clarify the association between TOB1
      expression and the clinical significance of this expression in patients with
      gastric carcinoma. Western blot analysis was performed to confirm the expression
      of TOB1 in gastric cancer. Immunohistochemistry (IHC) was performed on a tissue
      microarray containing 90 pairs of primary gastric cancer and adjacent normal
      tissue samples. TOB1 expression was evaluated separately with cytoplasmic and
      nuclear staining. Western blot analysis revealed significantly lower expression
      levels of TOB1 in gastric cancer tissues than those in adjacent normal tissues in
      91.7% of cases. This was confirmed by IHC, which revealed decreased cytoplasmic
      TOB1 expression in cancer tissues compared with those of normal tissue samples in
      84.4% of cases. The IHC data also revealed low cytoplasmic expression of TOB1 in
      67.8% of human gastric cancer samples. Nuclear TOB1 expression exhibited no
      significant association with specific pathological features. However, a
      significant association was identified between cytoplasmic expression levels of
      TOB1 and clinicopathological characteristics, including the depth of invasion
      (P=0.017), differentiation grade (P=0.034) and tumor-node-metastasis stage
      (P<0.000). In conclusion, cytoplasmic TOB1 expression was suggested to be
      significant in angiogenesis and cell differentiation in gastric cancer tissues
      and may be used as a potential prognostic marker.

PMID- 25760310
TI  - Electrical transport properties of Ge-doped GaN nanowires.
AB  - The conductivity and charge carrier concentration of single GaN nanowires (NWs)
      doped with different concentrations of Ge were determined by four-point
      resistivity and temperature-dependent Seebeck coefficient measurements. We
      observed high carrier concentrations ranging from 9.1 * 10(18) to 5.5 * 10(19)
      cm(-3), well above the Mott density of 1.6 * 10(18) cm(-3), and conductivities up
      to 625 S cm(-1) almost independent of the NW diameter. The weak temperature
      dependence of the conductivity between 2 and 10 K could be assigned to the
      formation of an impurity band. For the sample with the highest conductivity
      metallic behaviour was found, indicated by a positive temperature coefficient of
      the resistivity. The near band edge emission analyzed by micro-photoluminescence
      spectroscopy showed only a small increase of the peak width up to 70 meV and no
      spectral shift for carrier concentrations up to 5.5 * 10(19) cm(-3). The latter
      was attributed to the simultaneous influence of band filling, band gap
      renormalization, and strain. 

PMID- 25760311
TI  - Immunophenotype of simian immunodeficiency virus-infected cells in the spleen of
      a rhesus monkey.

PMID- 25760312
TI  - Role of blood and bone marrow examination in the diagnosis of mature lymphoid
      neoplasms in patients presenting with isolated splenomegaly.
AB  - OBJECTIVES: Mature lymphoid neoplasms presenting with 'prominent splenomegaly
      without significant lymphadenopathy' are uncommon and pose unique diagnostic
      challenges as compared to those associated with lymphadenopathy. Their
      descriptions in the literature are largely limited to a few case series. We
      analyzed the spectrum of these lymphomas diagnosed by peripheral blood (PB)
      and/or bone marrow (BM) examination. METHODS: Over a period of 6 years, 75
      patients were diagnosed with a lymphoma from PB/BM who had presented with
      predominant splenomegaly. Their clinical and laboratory records including PB and
      BM morphology; immunophenotyping using multi-parametric flow-cytometry and
      immunohistochemistry were reviewed. Wherever indicated, an extended panel of
      immunohistochemistry (IHC) was performed on BM biopsies for accurate sub
      classification. RESULTS AND DISCUSSION: The commonest lymphomas were hairy cell
      leukemia (HCL) (32%) and splenic marginal zone lymphoma (SMZL) (24%). Others
      included diffuse large B cell lymphoma (8%), chronic lymphocytic leukemia/small
      lymphocytic lymphoma (8%), mantle cell lymphoma (2.7%), and follicular lymphoma
      (1.3%), all of which usually presents with lymphadenopathy. SMZL was the
      commonest lymphoma among females and those with massive splenomegaly and
      lymphocytosis; while HCL was commonest in patients with pancytopenia. SMZL
      commonly presented with lymphocytosis; however, 22% of them also presented with
      pancytopenia. CONCLUSION: The high diagnostic efficacy of PB and BM examination
      using flow-cytometry and immunohistochemistry in confirming and sub-classifying
      splenic lymphomas suggests that a thorough hematological evaluation should always
      precede a diagnostic splenectomy. Immunohistochemistry remains the best modality
      to identify sparse or intra-sinusoidal infiltration on BM biopsy and is
      particularly useful in patients with fibrotic marrows and pancytopenia.

PMID- 25760313
TI  - Highly sensitive and selective fluorescent sensor for zinc ion based on a new
      diarylethene with a thiocarbamide unit.
AB  - A new photochromic diarylethene has been synthesized by using thiocarbamide as a
      functional group and perfluordiarylethene as photoswitching trigger via a
      salicylidene Schiff base linkage. The diarylethene could be used as a
      multicontrollable fluorescence switch when triggered by base/acid, light, and
      metal ions. The results showed that the absorption and fluorescence
      characteristics of the diarylethene exhibited sequence-dependent responses
      through efficient interaction of specific salicylidene Schiff base-linked
      thiocarbamide unit with tetrabutylammonium hydroxide/trifluoroacetic acid and
      photoirradiation. Moreover, the diarylethene was highly selective toward Zn(2+)
      ion with obvious fluorescence change from light blue to bright yellow in
      acetonitrile. The deprotonated form of the diarylethene had typical
      photochromism, but it showed an irreversible photocyclization reaction after
      binding with Zn(2+). Finally, two logic circuits were constructed by using the
      fluorescence intensity as the output signal with the inputs of the combinational
      stimuli of light and chemical species. 

PMID- 25760314
TI  - Purification and assembly of thermostable Cy5 labeled gamma-PNAs into a 3D DNA
      nanocage.
AB  - PNA is hybrid molecule ideally suited for bridging the functional landscape of
      polypeptides with the structural diversity that can be engineered with DNA
      nanostructures. However, PNA can be more challenging to work with in aqueous
      solvents due to its hydrophobic nature. A solution phase method using strain
      promoted, copper free click chemistry was developed to conjugate the fluorescent
      dye Cy5 to 2 bifunctional PNA strands as a first step toward building cyclic PNA
      polypeptides that can be arranged within 3D DNA nanoscaffolds. A 3D DNA nanocage
      was designed with binding sites for the 2 fluorescently labeled PNA strands in
      close proximity to mimic protein active sites. Denaturing polyacrylamide gel
      electrophoresis (PAGE) is introduced as an efficient method for purifying
      charged, dye-labeled PNA conjugates from large excesses of unreacted dye and
      unreacted, neutral PNA. Elution from the gel in water was monitored by
      fluorescence and found to be more efficient for the more soluble PNA strand.
      Native PAGE shows that both PNA strands hybridize to their intended binding sites
      within the DNA nanocage. Forster resonance energy transfer (FRET) with a Cy3
      labeled DNA nanocage was used to determine the dissociation temperature of one
      PNA-Cy5 conjugate to be near 50 degrees C. Steady-state and time resolved
      fluorescence was used to investigate the dye orientation and interactions within
      the various complexes. Bifunctional, thermostable PNA molecules are intriguing
      candidates for controlling the assembly and orientation of peptides within small
      DNA nanocages for mimicking protein catalytic sites. 

PMID- 25760315
TI  - Tracing nitrogenous disinfection byproducts after medium pressure UV water
      treatment by stable isotope labeling and high resolution mass spectrometry.
AB  - Advanced oxidation processes are important barriers for organic micropollutants
      (e.g., pharmaceuticals, pesticides) in (drinking) water treatment. Studies
      indicate that medium pressure (MP) UV/H2O2 treatment leads to a positive response
      in Ames mutagenicity tests, which is then removed after granulated activated
      carbon (GAC) filtration. The formed potentially mutagenic substances were
      hitherto not identified and may result from the reaction of photolysis products
      of nitrate with (photolysis products of) natural organic material (NOM). In this
      study we present an innovative approach to trace the formation of disinfection
      byproducts (DBPs) of MP UV water treatment, based on stable isotope labeled
      nitrate combined with high resolution mass spectrometry. It was shown that after
      MP UV treatment of artificial water containing NOM and nitrate, multiple nitrogen
      containing substances were formed. In total 84 N-DBPs were detected at individual
      concentrations between 1 to 135 ng/L bentazon-d6 equivalents, with a summed
      concentration of 1.2 MUg/L bentazon-d6 equivalents. The chemical structures of
      three byproducts were confirmed. Screening for the 84 N-DBPs in water samples
      from a full-scale drinking water treatment plant based on MP UV/H2O2 treatment
      showed that 22 of the N-DBPs found in artificial water were also detected in real
      water samples. 

PMID- 25760316
TI  - Self-injury and suicidality: the impact of trauma and dissociation.
AB  - In the growing research literature on nonsuicidal self-injury (NSSI) and
      suicidality (SA), there are many questions still unresolved about the role played
      by exposure to traumatic stressors (including but not limited to childhood
      maltreatment) and posttraumatic disorders (including dissociative features and
      disorders). In this special issue of the Journal of Trauma & Dissociation, a
      review article and 4 empirical studies attempt to provide additional insight into
      the relationship of traumatization and dissociation to NSSI and SA. The review
      article describes similarities and differences in the relationships that have
      been empirically documented between trauma exposure and posttraumatic stress or
      dissociative symptoms with NSSI versus SA and highlights the need for research to
      identify and test integrative clinical constructs, such as emotion dysregulation,
      in order to develop systematic risk, assessment, and intervention models. The
      empirical reports provide illustrative examples of conceptually and clinically
      integrated research on traumatic stress, dissociation, and NSSI and SA. Their
      findings offer a more nuanced picture of the potential role of different forms
      and degrees of dissociation in SA and NSSI and suggest that dissociation and
      emotion dysregulation may play a mediating role linking childhood maltreatment
      and adult or adolescent NSSI. In this introduction, we briefly summarize key
      points from the special issue articles and point out directions that their
      findings suggest for future research, including incorporating multiple predictors
      in studies of NSSI and SA, utilizing longitudinal studies to assess the etiology
      and course of NSSI and SA, and sampling diverse populations. 

PMID- 25760317
TI  - Positive and negative regulators of the metallothionein gene (review).
AB  - Metallothioneins (MTs) are metal-binding proteins involved in diverse processes,
      including metal homeostasis and detoxification, the oxidative stress response and
      cell proliferation. Aberrant expression and silencing of these genes are
      important in a number of diseases. Several positive regulators of MT genes,
      including metal-responsive element-binding transcription factor (MTF)-1 and
      upstream stimulatory factor (USF)-1, have been identified and mechanisms of
      induction have been well described. However, the negative regulators of MT genes
      remain to be elucidated. Previous studies from the group of the present review
      have revealed that the hematopoietic master transcription factor, PU.1, directly
      represses the expression levels of MT genes through its epigenetic activities,
      and upregulation of MT results in the potent inhibition of myeloid
      differentiation. The present review focuses on PU.1 and several other negative
      regulators of this gene, including PZ120, DNA methyltransferase 3a with Mbd3 and
      Brg1 complex, CCAAT enhancer binding protein alpha and Ku protein, and describes
      the suppression of the MT genes through these transcription factors.

PMID- 25760318
TI  - Redox cycloisomerization approach to 1,2-dihydropyridines.
AB  - The phosphine-catalyzed synthesis of 1,2-dihydropyridines via an alkyne
      isomerization/electrocyclization sequence is described. Propargylidenecarbamate
      substrates were prepared following a one-pot procedure between a terminal alkyne,
      a benzonitrile, and a chloroformate in the presence of trimethylaluminum. This
      methodology gives access to a diverse set of 2,6-disubstituted 1,2
      dihydropyridines in high yield. The products can be easily converted into
      substituted piperidines or pyridines, and this methodology was applied to the
      synthesis of indolizidines. 

PMID- 25760319
TI  - Positive attitudes and person-centred care predict of sense of competence in
      dementia care staff.
AB  - OBJECTIVES: The number of people who will require institutional care for dementia
      is rapidly rising. This increase raises questions about how the workforce can
      meet the challenge of providing quality care. A promising psychological concept
      that could improve staff and care recipient outcomes is staff sense of competence
      in their capacity to provide dementia care. The purpose of this study was to
      elucidate the relative importance of staff factors associated with sense of
      competence. METHOD: Sixty-one Australian dementia care staff (mostly nurses, 69%;
      and allied health, 21%) were recruited. Measures included the Sense of Competence
      in Dementia Care Staff (criterion) and standardised measures of empirically
      derived predictors: training, knowledge, attitudes and person-centred care
      strategies. RESULTS: Standard multiple regression revealed that 33.9% of the
      variance in sense of competence was explained by the combination of the four
      predictors. Attitudes and person-centred strategies each uniquely explained a
      moderate amount of variance, while training and knowledge were not significant
      predictors of sense of competence. CONCLUSION: A positive attitude towards people
      with dementia, and stronger intentions to implement person-centred care
      strategies, predicted a greater sense of competence to provide care, whereas
      knowledge and training, commonly believed to be important contributors to sense
      of competence in dementia care, did not predict this outcome. Investing in
      strategies that address staff attitude and encourage person-centred care could
      influence sense of competence, and by extension, dementia care.

PMID- 25760320
TI  - Relationship between patients' outcomes and the changes in serum creatinine and
      urine output and RIFLE classification in a large critical care cohort database.
AB  - We report the stepwise application of the RIFLE classification in 155,624
      admissions in the UK Intensive Care National Audit & Research Centre Case Mix
      Programme database. The assumptions required to define RIFLE and their
      relationship with renal replacement therapy (RRT) and ICU mortality were
      assessed. Previous reports had not explored the method of estimating baseline
      creatinine, the position of class boundaries, or interactions between urine
      volume (AKI-U) and the peak/estimated baseline creatinine (AKI-Cr) within 24 h of
      ICU admission. The risk of developing AKI strongly depended on the assumed GFR
      increasing from 36 to 58% across the recommended range. AKI-U was often seen
      without AKI-Cr, and moderate oliguria (under 850 ml/24 h) was a stronger
      predictor of mortality than any degree of AKI-Cr partly because mortality fell
      when peak/estimated baseline creatinine ratios exceed fourfold. Mild oliguria
      (850-1500 ml/24 h) was common (38,928 admissions, 26%) and had a similar
      association with mortality (relative risk 1.6, 95% CI: 1.5-1.6) as did AKI-Cr
      defined Failure (risk ratio 1.5, 95% CI: 1.5-1.6). However, AKI-Cr was a strong
      predictor for RRT, which was used in 17,802 (11%) of admissions. Nearly half
      (48%) of the Failure patients never received RRT; nonetheless, most (66%)
      survived critical care. Thus, although the RIFLE classification may be attempted
      in large population cohorts, there is significant heterogeneity of both renal
      and, in particular, vital outcomes within each class. 

PMID- 25760321
TI  - Urinary ammonia and long-term outcomes in chronic kidney disease.
AB  - Recent studies suggest that alkalinizing treatments improve the course of chronic
      kidney disease (CKD), even in patients without overt metabolic acidosis. Here, we
      tested whether a decreased ability in excreting urinary acid rather than overt
      metabolic acidosis may be deleterious to the course of CKD. We studied the
      associations between baseline venous total CO2 concentration or urinary ammonia
      excretion and long-term CKD outcomes in 1065 patients of the NephroTest cohort
      with CKD stages 1-4. All patients had measured glomerular filtration rate (mGFR)
      by (51)Cr-EDTA renal clearance. Median mGFR at baseline was 37.6 ml/min per 1.73
      m(2). Urinary ammonia excretion decreased with GFR, whereas net endogenous acid
      production did not. After a median follow-up of 4.3 years, 201 patients reached
      end-stage renal disease (ESRD) and 114 died before ESRD. Twenty-six percent of
      the patients had mGFR decline rate greater than 10% per year. Compared with
      patients in the highest tertile of urinary ammonia excretion, those in the lowest
      tertile had a significantly increased hazard ratio for ESRD, 1.82 (95% CI, 1.06
      3.13), and a higher odds ratio of fast mGFR decline, 1.84 (0.98-3.48),
      independent of mGFR and other confounders. Patients in the lowest tertile of
      venous total CO2 had significantly increased risk of fast mGFR decline but not of
      ESRD. None of these biomarkers was associated with mortality. Thus, these results
      suggest that the inability to excrete the daily acid load is deleterious to renal
      outcomes. 

PMID- 25760324
TI  - A dearth of data: the problem of phosphorus in prescription medications.
AB  - A high dietary intake of phosphorus is considered by most to be a significant
      health threat for dialysis patients. Efforts to include the phosphorus content of
      foods on the nutrition label in the US have, to date, been fruitless. Another
      source of phosphorus, largely unrecognized, is prescription medications. These
      may contain phosphorus as indicated on their package label; the amount is not
      quantified. We examined the labels of the branded forms of 200 of the most widely
      prescribed medications in Dialysis Clinic centers in the United States and found
      that 23 (11.5%) contained phosphorus. A sampling of different doses and
      manufacturers (generic and branded) of these drugs was analyzed for phosphorus
      content and found levels as high as 111.5 mg/dose (40 mg paroxetine). Notable
      were the phosphorus content of a generic 10 mg lisinopril (32.6 mg) and a generic
      10 mg amlodipine (40.1 mg). The significant potential for iatrogenic injury
      accruing from the use of these drugs warrants efforts at remediation. Specific
      information on the phosphorus content of medications used by dialysis population
      needs to be made available to the dialysis community. 

PMID- 25760322
TI  - Telomerase deficiency delays renal recovery in mice after ischemia-reperfusion
      injury by impairing autophagy.
AB  - The aged population suffers increased morbidity and higher mortality in response
      to episodes of acute kidney injury (AKI). Aging is associated with telomere
      shortening, and both telomerase reverse transcriptase (TerT) and RNA (TerC) are
      essential to maintain telomere length. To define a role of telomerase deficiency
      in susceptibility to AKI, we used ischemia/reperfusion injury in wild-type mice
      or mice with either TerC or TerT deletion. Injury induced similar renal
      impairment at day 1 in each genotype, as assessed by azotemia, proteinuria, acute
      tubular injury score, and apoptotic tubular epithelial cell index. However,
      either TerC or TerT knockout significantly delayed recovery compared with wild
      type mice. Electron microscopy showed increased autophagosome formation in renal
      tubular epithelial cells in wild-type mice but a significant delay of their
      development in TerC and TerT knockout mice. There were also impeded increases in
      the expression of the autophagosome marker LC3 II, prolonged accumulation of the
      autophagosome protein P62, an increase of the cell cycle regulator p16, and
      greater activation of the mammalian target of rapamycin (mTOR) pathway. The
      mTORC1 inhibitor, rapamycin, partially restored the ischemia/reperfusion-induced
      autophagy response, without a significant effect on either p16 induction or
      tubule epithelial cell proliferation. Thus, muting the maintenance of normal
      telomere length in mice impaired recovery from AKI, owing to an increase in
      tubule cell senescence and impairment of mTOR-mediated autophagy. 

PMID- 25760323
TI  - Cannabinoid receptor 1 is a major mediator of renal fibrosis.
AB  - Chronic kidney disease, secondary to renal fibrogenesis, is a burden on public
      health. There is a need to explore new therapeutic pathways to reduce renal
      fibrogenesis. To study this, we used unilateral ureteral obstruction (UUO) in
      mice as an experimental model of renal fibrosis and microarray analysis to
      compare gene expression in fibrotic and normal kidneys. The cannabinoid receptor
      1 (CB1) was among the most upregulated genes in mice, and the main endogenous CB1
      ligand (2-arachidonoylglycerol) was significantly increased in the fibrotic
      kidney. Interestingly, CB1 expression was highly increased in kidney biopsies of
      patients with IgA nephropathy, diabetes, and acute interstitial nephritis. Both
      genetic and pharmacological knockout of CB1 induced a profound reduction in renal
      fibrosis during UUO. While CB2 is also involved in renal fibrogenesis, it did not
      potentiate the role of CB1. CB1 expression was significantly increased in
      myofibroblasts, the main effector cells in renal fibrogenesis, upon TGF-beta1
      stimulation. The decrease in renal fibrosis during CB1 blockade could be
      explained by a direct action on myofibroblasts. CB1 blockade reduced collagen
      expression in vitro. Rimonabant, a selective CB1 endocannabinoid receptor
      antagonist, modulated the macrophage infiltrate responsible for renal fibrosis in
      UUO through a decrease in monocyte chemoattractant protein-1 synthesis. Thus, CB1
      has a major role in the activation of myofibroblasts and may be a new target for
      treating chronic kidney disease. 

PMID- 25760325
TI  - Renal fibrosis is not reduced by blocking transforming growth factor-beta
      signaling in matrix-producing interstitial cells.
AB  - Transforming growth factor-beta (TGF-beta) strongly promotes renal
      tubulointerstitial fibrosis, but the cellular target that mediates its
      profibrotic actions has not been clearly identified. While in vitro data suggest
      that TGF-beta-induced matrix production is mediated by renal fibroblasts, the
      role of these cells in TGF-beta-dependent tubulointerstitial fibrosis following
      renal injury is not well defined. To address this, we deleted the TGF-beta type
      II receptor in matrix-producing interstitial cells using two different inducible
      Cre models: COL1A2-Cre with a mesenchymal enhancer element and tenascin-Cre that
      targets medullary interstitial cells, and either the mouse unilateral ureteral
      obstruction or the aristolochic acid renal injury model. Renal interstitial cells
      lacking the TGF-beta receptor had significantly impaired collagen I production,
      but, unexpectedly, overall tissue fibrosis was unchanged in the conditional
      knockouts after renal injury. Thus, abrogating TGF-beta signaling in matrix
      producing interstitial cells is not sufficient to reduce fibrosis after renal
      injury. 

PMID- 25760326
TI  - Targeted inhibitory effect of Lenti-SM22alpha-p27-EGFP recombinant lentiviral
      vectors on proliferation of vascular smooth muscle cells without compromising re
      endothelialization in a rat carotid artery balloon injury model.
AB  - AIMS: In-stent restenosis remains a serious problem after the implantation of
      drug-eluting stents, which is attributable to neointima formation and re
      endothelialization. Here, we tried to find a new method which aims at selectively
      inhibiting proliferation of vascular smooth muscle cells (VSMC) proliferation
      without inhibition of re-endothelialization. METHODS AND RESULTS: We used the
      smooth muscle-specific SM22alpha promoter in a recombinant lentiviral vector to
      drive overexpression of cell-cycle inhibitor, p27, in VSMCs. p27 effectively
      inhibited VSMC proliferation mediated by cell cycle arrest at the G0/G1
      checkpoint. The SM22alpha-p27 lentiviral vector inhibited VSMC proliferation more
      effectively than paclitaxel. Rats infected with Lenti-SM22alpha-p27 had a
      significantly lower intima/media (I/M) ratio and also showed inhibition of
      restenosis on day 28 after balloon injury. Moreover, the repair of injured
      endothelium, and re-endothelialization of the carotid artery wall, was not
      affected by the smooth muscle cell-specific expression of p27. CONCLUSION: A
      recombinant lentiviral vector carrying the SM22alpha promoter was used to
      effectively infect and selectively overexpress p27 protein in VSMCs, leading to
      inhibition of intimal hyperplasia without compromising endothelial repair.

PMID- 25760327
TI  - Will they stay or will they go? International graduate students and their
      decisions to stay or leave the U.S. upon graduation.
AB  - The U.S. currently enjoys a position among the world's foremost innovative and
      scientifically advanced economies but the emergence of new economic powerhouses
      like China and India threatens to disrupt the global distribution of innovation
      and economic competitiveness. Among U.S. policy makers, the promotion of advanced
      education, particularly in the STEM (Science, Technology, Engineering and
      Mathematics) fields, has become a key strategy for ensuring the U.S.'s position
      as an innovative economic leader. Since approximately one third of science and
      engineering post-graduate students in the U.S. are foreign born, the future of
      the U.S. STEM educational system is intimately tied to issues of global
      competitiveness and American immigration policy. This study utilizes a
      combination of national education data, a survey of foreign-born STEM graduate
      students, and in-depth interviews of a sub-set of those students to explain how a
      combination of scientists' and engineers' educational decisions, as well as their
      experience in school, can predict a students' career path and geographical
      location, which can affect the long-term innovation environment in their home and
      destination country. This study highlights the fact that the increasing global
      competitiveness in STEM education and the complex, restrictive nature of U.S.
      immigration policies are contributing to an environment where the American STEM
      system may no longer be able to comfortably remain the premier destination for
      the world's top international students. 

PMID- 25760328
TI  - Early development and orientation of the acoustic funnel provides insight into
      the evolution of sound reception pathways in cetaceans.
AB  - Whales receive underwater sounds through a fundamentally different mechanism than
      their close terrestrial relatives. Instead of hearing through the ear canal,
      cetaceans hear through specialized fatty tissues leading to an evolutionarily
      novel feature: an acoustic funnel located anterior to the tympanic aperture. We
      traced the ontogenetic development of this feature in 56 fetal specimens from 10
      different families of toothed (odontocete) and baleen (mysticete) whales, using X
      ray computed tomography. We also charted ear ossification patterns through
      ontogeny to understand the impact of heterochronic developmental processes. We
      determined that the acoustic funnel arises from a prominent V-shaped structure
      established early in ontogeny, formed by the malleus and the goniale. In
      odontocetes, this V-formation develops into a cone-shaped funnel facing
      anteriorly, directly into intramandibular acoustic fats, which is likely
      functionally linked to the anterior orientation of sound reception in
      echolocation. In contrast, the acoustic funnel in balaenopterids rotates
      laterally, later in fetal development, consistent with a lateral sound reception
      pathway. Balaenids and several fossil mysticetes retain a somewhat anteriorly
      oriented acoustic funnel in the mature condition, indicating that a lateral sound
      reception pathway in balaenopterids may be a recent evolutionary innovation
      linked to specialized feeding modes, such as lunge-feeding. 

PMID- 25760329
TI  - Hearing loss and cognition: the role of hearing AIDS, social isolation and
      depression.
AB  - Hearing loss is associated with poor cognitive performance and incident dementia
      and may contribute to cognitive decline. Treating hearing loss with hearing aids
      may ameliorate cognitive decline. The purpose of this study was to test whether
      use of hearing aids was associated with better cognitive performance, and if this
      relationship was mediated via social isolation and/or depression. Structural
      equation modelling of associations between hearing loss, cognitive performance,
      social isolation, depression and hearing aid use was carried out with a subsample
      of the UK Biobank data set (n = 164,770) of UK adults aged 40 to 69 years who
      completed a hearing test. Age, sex, general health and socioeconomic status were
      controlled for as potential confounders. Hearing aid use was associated with
      better cognition, independently of social isolation and depression. This finding
      was consistent with the hypothesis that hearing aids may improve cognitive
      performance, although if hearing aids do have a positive effect on cognition it
      is not likely to be via reduction of the adverse effects of hearing loss on
      social isolation or depression. We suggest that any positive effects of hearing
      aid use on cognition may be via improvement in audibility or associated increases
      in self-efficacy. Alternatively, positive associations between hearing aid use
      and cognition may be accounted for by more cognitively able people seeking and
      using hearing aids. Further research is required to determine the direction of
      association, if there is any direct causal relationship between hearing aid use
      and better cognition, and whether hearing aid use results in reduction in rates
      of cognitive decline measured longitudinally. 

PMID- 25760331
TI  - Identification of a novel dehydroergosterol enhancing microglial anti
      inflammatory activity in a dairy product fermented with Penicillium candidum.
AB  - Despite the ever-increasing number of dementia patients worldwide, fundamental
      therapeutic approaches to treat this disease remain to be established. Preventive
      approaches such as diet, exercise and learning attract attention. Several
      epidemiological studies suggest that ingestion of fermented dairy products
      prevents cognitive decline in the elderly. These reports indicate that specific
      ingredients in the fermented dairy products elicit an anti-inflammatory or anti
      oxidative activity that facilitates neuroprotection. The responsible components
      remain to be investigated. A number of studies have shown that inflammation
      caused by microglia is closely related to exaggeration of the pathology and
      cognitive decline seen in the elderly. Many researchers have proposed that
      controlling microglial activities could be effective in preventing and possibly
      curing dementia. In the present study, to elucidate specific compounds that
      regulate microglial activity from dairy products, repeated purification by HPLC,
      combined with evaluation using primary microglia, facilitated the identification
      of dehydroergosterol (DHE) as a novel component of the extract that enhances
      microglial anti-inflammatory activity. DHE contains three conjugated double bonds
      in a steroid ring system and is an analogue of ergosterol. Despite their related
      chemical structures, the anti-inflammatory activity of DHE is markedly stronger
      than that of ergosterol. P. candidum for camembert cheese produces DHE, but P.
      Roqueforti for blue cheese and Aspergillus do not. DHE also induces CD11b
      positive microglia cells into CD206-positive M2 type microglia. Neurotoxicity and
      neuronal cell death induced by excessively activated microglia is suppressed by
      treatment with DHE. Thus, this is the first report to demonstrate that DHE,
      identified as a responsible compound in dairy products, can induce microglia into
      a preferable phenotype for our brain environment and can be safely introduced
      into the body by consumption of dairy products. We believe the uptake of DHE
      might help to prevent the onset of dementia. 

PMID- 25760330
TI  - Dependence of intracellular and exosomal microRNAs on viral E6/E7 oncogene
      expression in HPV-positive tumor cells.
AB  - Specific types of human papillomaviruses (HPVs) cause cervical cancer. Cervical
      cancers exhibit aberrant cellular microRNA (miRNA) expression patterns. By genome
      wide analyses, we investigate whether the intracellular and exosomal miRNA
      compositions of HPV-positive cancer cells are dependent on endogenous E6/E7
      oncogene expression. Deep sequencing studies combined with qRT-PCR analyses show
      that E6/E7 silencing significantly affects ten of the 52 most abundant
      intracellular miRNAs in HPV18-positive HeLa cells, downregulating miR-17-5p, miR
      186-5p, miR-378a-3p, miR-378f, miR-629-5p and miR-7-5p, and upregulating miR-143
      3p, miR-23a-3p, miR-23b-3p and miR-27b-3p. The effects of E6/E7 silencing on
      miRNA levels are mainly not dependent on p53 and similarly observed in HPV16
      positive SiHa cells. The E6/E7-regulated miRNAs are enriched for species involved
      in the control of cell proliferation, senescence and apoptosis, suggesting that
      they contribute to the growth of HPV-positive cancer cells. Consistently, we show
      that sustained E6/E7 expression is required to maintain the intracellular levels
      of members of the miR-17~92 cluster, which reduce expression of the anti
      proliferative p21 gene in HPV-positive cancer cells. In exosomes secreted by HeLa
      cells, a distinct seven-miRNA-signature was identified among the most abundant
      miRNAs, with significant downregulation of let-7d-5p, miR-20a-5p, miR-378a-3p,
      miR-423-3p, miR-7-5p, miR-92a-3p and upregulation of miR-21-5p, upon E6/E7
      silencing. Several of the E6/E7-dependent exosomal miRNAs have also been linked
      to the control of cell proliferation and apoptosis. This study represents the
      first global analysis of intracellular and exosomal miRNAs and shows that viral
      oncogene expression affects the abundance of multiple miRNAs likely contributing
      to the E6/E7-dependent growth of HPV-positive cancer cells. 

PMID- 25760333
TI  - Versatile approaches to target staphylococcal infections.

PMID- 25760334
TI  - Drug repurposing for the treatment of staphylococcal infections.
AB  - The development and approval of new antimicrobials capable of being used to treat
      infections caused by multidrug-resistant pathogens has not kept pace with the
      rapid emergence of bacterial resistance. Without a doubt, there is a critical
      unmet need for the identification of novel strategies to develop antimicrobials
      to deal with this new scourge. One strategy, which warrants special attention as
      a unique method for identifying new antimicrobials, is drug repurposing. Several
      approved drugs have been successfully repurposed for different ailments giving
      hope that this strategy can also be utilized to uncover new antibacterials. To
      aid in this process, the present review presents non-antimicrobial approved drugs
      and clinical molecules, which have been shown to possess antimicrobial activity
      against Staphylococcus aureus and their potential clinical applications.
      Additionally, approved drugs with novel applications such as interference in
      staphylococcal pathogenesis and host immunomodulators are also explained. The
      current review also discusses the challenges associated with repurposing already
      approved non-antimicrobial drugs as antibacterials and potential uses of these
      drugs that can be further explored in order to develop novel therapeutics for the
      treatment of multidrug- resistant staphylococcal infections. Collectively, the
      information presented demonstrates that repurposing approved drugs and clinical
      molecules as antimicrobials may help to speed up the drug development process and
      save years of expensive research invested in antimicrobial drug development.

PMID- 25760335
TI  - Beyond numbers: the informative patterns of immuno-staphylococcal dynamics.
AB  - To evaluate new drugs, the immune system should be considered. Here we evaluated
      a proof-of-concept that uncovers bacterial-leukocyte interactions. Analyzing
      longitudinal leukocyte data from bovines infected with either methicillin
      resistant (MRSA) or methicillin-susceptible (MSSA) Staphylococcus aureus, two
      methods were investigated: (i) an approach that assesses lymphocytes, monocytes,
      or neutrophils, separately, and (ii) a method that, using dimensionless
      indicators (products, ratios, or combinations derived from leukocyte data),
      explores the dynamics of leukocyte relationships in three-dimensional (3D) space
      and identifies data subsets of informative value. The classic approach not always
      distinguished infected from non-infected cows. In contrast, the alternative
      approach differentiated noninfected from infected animals and distinguished early
      MRSA from early MSSA and late MRSA infections. Discrimination was associated with
      the use of dimensionless indicators. When measured in 3D space, such indicators
      generated a very large number of combinations, which helped detect data subsets
      usually unobserved, such as non-overlapping infection-negative and -positive
      subsets, and several disease stages. The validity of such data subsets was
      determined with biologically interpretable data. This graphic, pattern
      recognition-based information system included but did not depend on any one
      number or variable. Because it can detect functions (relationships that involve
      two or more elements), in real time, if shown reproducible, the analysis of
      complex host-microbial dynamics could be used to evaluate antimicrobials.

PMID- 25760332
TI  - Microbial iron mats at the Mid-Atlantic Ridge and evidence that
      Zetaproteobacteria may be restricted to iron-oxidizing marine systems.
AB  - Chemolithoautotrophic iron-oxidizing bacteria play an essential role in the
      global iron cycle. Thus far, the majority of marine iron-oxidizing bacteria have
      been identified as Zetaproteobacteria, a novel class within the phylum
      Proteobacteria. Marine iron-oxidizing microbial communities have been found
      associated with volcanically active seamounts, crustal spreading centers, and
      coastal waters. However, little is known about the presence and diversity of iron
      oxidizing communities at hydrothermal systems along the slow crustal spreading
      center of the Mid-Atlantic Ridge. From October to November 2012, samples were
      collected from rust-colored mats at three well-known hydrothermal vent systems on
      the Mid-Atlantic Ridge (Rainbow, Trans-Atlantic Geotraverse, and Snake Pit) using
      the ROV Jason II. The goal of these efforts was to determine if iron-oxidizing
      Zetaproteobacteria were present at sites proximal to black smoker vent fields.
      Small, diffuse flow venting areas with high iron(II) concentrations and rust
      colored microbial mats were observed at all three sites proximal to black smoker
      chimneys. A novel, syringe-based precision sampler was used to collect discrete
      microbial iron mat samples at the three sites. The presence of Zetaproteobacteria
      was confirmed using a combination of 16S rRNA pyrosequencing and single-cell
      sorting, while light micros-copy revealed a variety of iron-oxyhydroxide
      structures, indicating that active iron-oxidizing communities exist along the Mid
      Atlantic Ridge. Sequencing analysis suggests that these iron mats contain
      cosmopolitan representatives of Zetaproteobacteria, but also exhibit diversity
      that may be uncommon at other iron-rich marine sites studied to date. A meta
      analysis of publically available data encompassing a variety of aquatic habitats
      indicates that Zetaproteobacteria are rare if an iron source is not readily
      available. This work adds to the growing understanding of Zetaproteobacteria
      ecology and suggests that this organism is likely locally restricted to iron-rich
      marine environments but may exhibit wide-scale geographic distribution, further
      underscoring the importance of Zetaproteobacteria in global iron cycling. 

PMID- 25760336
TI  - Driving Forces of Mechanisms Regulating Oxacillin-Resistance Phenotypes of MRSA:
      Truly Oxacillin-Susceptible mecA-Positive Staphylococcus aureus Clinical Isolates
      also Exist.
AB  - As MRSA are considered Staphylococcus aureus isolates with oxacillin minimum
      inhibitory concentration (MIC) of &#8805;4 mg/L or harboring the mecA gene.
      However, the presence of mecA does not necessarily lead to oxacillin resistance
      and mecA gene-carrying isolates may have oxacillin MIC within the susceptible
      range (&#8805;2 mg/L). During the last few years it has become apparent that
      oxacillin-susceptible (OS) mecA-positive S. aureus isolates (commonly called OS
      MRSA) are rather commonly detected worldwide and may remain undiagnosed using
      phenotypic susceptibility testing methods. This review will summarize the current
      reports on OS-MRSA isolations and the underlying mechanisms regulating the
      expression of oxacillin resistance and also oxacillin susceptibility in mecA
      positive S. aureus isolates. As MRSA commonly cause severe infections against
      which effective therapies are limited, understanding of these mechanisms could
      enable the identification of new targets for the treatment or reversion of the
      MRSA phenotype. 

PMID- 25760337
TI  - Significant Differences Characterise the Correlation Coefficients between Biocide
      and Antibiotic Susceptibility Profiles in Staphylococcus aureus.
AB  - There is a growing concern by regulatory authorities for the selection of
      antibiotic resistance caused by the use of biocidal products. We aimed to
      complete the detailed information on large surveys by investigating the
      relationship between biocide and antibiotic susceptibility profiles of a large
      number of Staphylococcus aureus isolates using four biocides and antibiotics
      commonly used in clinical practice. The minimal inhibitory concentration (MIC)
      for most clinically-relevant antibiotics was determined according to the
      standardized methodology for over 1600 clinical S. aureus isolates and compared
      to susceptibility profiles of benzalkonium chloride, chlorhexidine, triclosan,
      and sodium hypochlorite. The relationship between antibiotic and biocide
      susceptibility profiles was evaluated using non-linear correlations. The main
      outcome evidenced was an absence of any strong or moderate statistically
      significant correlation when susceptibilities of either triclosan or sodium
      hypochlorite were compared for any of the tested antibiotics. On the other hand,
      correlation coefficients for MICs of benzalkonium chloride and chlorhexidine were
      calculated above 0.4 for susceptibility to quinolones, beta-lactams, and also
      macrolides. Our data do not support any selective pressure for association
      between biocides and antibiotics resistance and furthermore do not allow for a
      defined risk evaluation for some of the compounds. Importantly, our data clearly
      indicate that there does not involve any risk of selection for antibiotic
      resistance for the compounds triclosan and sodium hypochlorite. These data hence
      infer that biocide selection for antibiotic resistance has had so far a less
      significant impact than feared. 

PMID- 25760338
TI  - Antimicrobial peptides and peptidomimetics - potent therapeutic allies for
      staphylococcal infections.
AB  - The pervasiveness of bacterial resistance to conventional antibiotics,
      particularly those associated with staphylococcal infections, has become a global
      epidemic. However, research involving antimicrobial peptides (AMPs) and their
      synthetic analogues has unearthed a potentially novel class of antibacterials for
      the treatment of an array of diseases caused by pathogenic bacteria, such as
      staphylococci. AMPs have several unique advantages over traditional antibiotics
      such as the projected slow emergence of bacterial resistance to these agents and
      their capability to modulate the host immune response to infection.
      Unfortunately, their susceptibility to proteolytic degradation, loss of
      antimicrobial activity due to serum binding or physiological concentration of
      salts, and toxicity to host tissues has limited their use as systemic agents thus
      far. Additionally, the presence of economic and regulatory obstacles has hindered
      the translation of AMPs, as antimicrobials, from the bench to the clinic. The
      present review delves further into the benefits and challenges of utilizing AMPs
      as antibacterial agents (particularly for staphylococcal infections), the methods
      which have been utilized to overcome their limitations, their successes and
      failures in clinical trials, and future avenues for researchers to pursue to
      develop AMPs as novel therapeutic allies in the treatment of bacterial
      infections.

PMID- 25760339
TI  - Harnessing the power of light to treat staphylococcal infections focusing on
      MRSA.
AB  - Methicillin-resistant Staphylococcus aureus (MRSA) has become the most important
      drug-resistant microbial pathogen in countries throughout the world. Morbidity
      and mortality due to MRSA infections continue to increase despite efforts to
      improve infection control measures and to develop new antibiotics. Therefore
      alternative antimicrobial strategies that do not give rise to development of
      resistance are urgently required. A group of therapeutic interventions has been
      developed in the field of photomedicine with the common theme that they rely on
      electromagnetic radiation with wavelengths between 200 and 1000 nm broadly called
      "light". These techniques all use simple absorption of photons by specific
      chromophores to deliver the killing blow to microbial cells while leaving the
      surrounding host mammalian cells relatively unharmed. Photodynamic inactivation
      uses dyes called photosensitizers (PS) that bind specifically to MRSA cells and
      not host cells, and generate reactive oxygen species including singlet oxygen and
      singlet oxygen upon illumination. Sophisticated molecular strategies to target
      the PS to MRSA cells have been designed. Ultraviolet C radiation can damage
      microbial DNA without unduly harming host DNA. Blue light can excite endogenous
      porphyrins and flavins in MRSA cells that are not present in host cells. Near
      infrared lasers can interfere with microbial membrane potentials without raising
      the temperature of the tissue. Taken together these innovative approaches towards
      harnessing the power of light suggest that the ongoing threat of MRSA may
      eventually be defeated. 

PMID- 25760340
TI  - Therapeutic options and emerging alternatives for multidrug resistant
      staphylococcal infections.
AB  - Methicillin-resistant Staphylococcus aureus (MRSA) remains the single biggest
      challenge in infectious disease in the civilized world. Moreover, vancomycin
      resistance is also spreading, leading to fears of untreatable infections as were
      common in ancient times. Molecular microbiology and bioinformatics have revealed
      many of the mechanisms involved in resistance development. Mobile genetic
      elements, up-regulated virulence factors and multi-drug efflux pumps have been
      implicated. A range of approved antibiotics from the glycopeptide, lipopeptide,
      pleuromutilin, macrolide, oxazolidinone, lincosamide, aminoglycoside,
      tetracycline, steptogramin, and cephalosporin classes has been employed to treat
      MRSA infections. The upcoming pipeline of drugs for MRSA includes some new
      compounds from the above classes, together with fluoroquinolones, antibacterial
      peptide mimetics, aminomethylciclines, porphyrins, peptide deformylase
      inhibitors, oxadiazoles, and diaminopyrimidines. A range of non-drug alternative
      approaches has emerged for MRSA treatment. Bacteriophage-therapy including
      purified lysins has made a comeback after being discovered in the 1930s. Quorum
      sensing inhibitors are under investigation. Small molecule inhibitors of multi
      drug efflux pumps may potentiate existing antibiotics. The relative failure of
      staphylococcal vaccines is being revisited by efforts with multi-valent vaccines
      and improved adjuvants. Photodynamic therapy uses non-toxic photosensitizers and
      harmless visible light to produce reactive oxygen species that can
      nonspecifically destroy bacteria while preserving host cells. Preparation of
      nanoparticles can kill bacteria themselves, as well as improve the delivery of
      anti-bacterial drugs. Anti-MRSA drug discovery remains an exciting field with
      great promise for the future. 

PMID- 25760341
TI  - Staphylococcus aureus: Current State of Prevalence, Impact, and Vaccine
      Development.
AB  - Staphylococcus aureus is a fastidious pathogen of global concern. S. aureus can
      not only cause a wide range of serious infections, but can also colonize healthy
      individuals. Nosocomial- associated S. aureus infection is a major concern for
      healthcare facilities. Recent increases in antibiotic resistance and community
      acquired infection highlight the need for improved understanding for prevention
      and treatment of this pathogen. This minireview addresses the current state of S.
      aureus prevalence, correlates of immunity, and vaccine development. 

PMID- 25760342
TI  - Inhibition of Quorum Sensing in Staphylococcus spp.
AB  - The Gram-positive, facultative anaerobic coccus-shaped bacteria of the genus
      Staphylococcus are among the most important causative agents of acute and chronic
      bacterial infections in humans as well as in animals. Treatment of Staphylococcus
      infections has become increasingly challenging due to the growing problem of
      antibiotic resistance. For this reason innovative antimicrobials with novel
      targets and modes of action are needed. Since the discovery that QS is used by
      Staphylococcus spp. to coordinate the expression of several genes involved in
      virulence, biofilm formation and pathogenicity, QS inhibition has gained
      increasing attention as an alternative anti-pathogenic strategy. A major
      advantage compared with antibiotic therapy is that QSIs are used in
      concentrations that do not affect bacterial growth. For this reason, it is
      expected that these compounds would exert less pressure towards the development
      of resistance. However, some important points still need to be addressed.
      Although several inhibitors have proven to be active antipathogenic agents in
      vitro and in several in vivo models, it is still unknown whether these compounds
      will also be useful in humans. Furthermore, several fundamental mechanisms by
      which the different QS systems in Staphylococcus spp. exert their regulatory
      functions and how they are inhibited by QSIs are still poorly understood. In
      order to achieve real-life applications with QSIs, these challenges should be
      addressed and more research will be needed. In this article, we will discuss the
      different QS systems present in Staphylococcus spp., how they are used to control
      virulence and biofilm formation and how they can be blocked. 

PMID- 25760343
TI  - Descriptive anatomy and three-dimensional reconstruction of the skull of the
      early tetrapod Acanthostega gunnari Jarvik, 1952.
AB  - The early tetrapod Acanthostega gunnari is an iconic fossil taxon exhibiting
      skeletal morphology reflecting the transition of vertebrates from water onto
      land. Computed tomography data of two Acanthostega skulls was segmented using
      visualization software to digitally separate bone from matrix and individual
      bones of the skull from each other. A revised description of cranial and lower
      jaw anatomy in this taxon based on CT data includes new details of sutural
      morphology, the previously undescribed quadrate and articular bones, and the
      mandibular symphysis. Sutural morphology is used to infer loading regime in the
      skull during feeding, and suggests Acanthostega used its anterior jaws to
      initially seize prey while smaller posterior teeth were used to restrain
      struggling prey during ingestion. Novel methods were used to repair and
      retrodeform the skull, resulting in a three-dimensional digital reconstruction
      that features a longer postorbital region and more strongly hooked anterior lower
      jaw than previous attempts while supporting the presence of a midline gap between
      the nasals and median rostrals. 

PMID- 25760344
TI  - Cis-regulatory mechanisms for robust olfactory sensory neuron class-restricted
      odorant receptor gene expression in Drosophila.
AB  - Odor perception requires that each olfactory sensory neuron (OSN) class
      continuously express a single odorant receptor (OR) regardless of changes in the
      environment. However, little is known about the control of the robust, class
      specific OR expression involved. Here, we investigate the cis-regulatory
      mechanisms and components that generate robust and OSN class-specific OR
      expression in Drosophila. Our results demonstrate that the spatial restriction of
      expression to a single OSN class is directed by clusters of transcription-factor
      DNA binding motifs. Our dissection of motif clusters of differing complexity
      demonstrates that structural components such as motif overlap and motif order
      integrate transcription factor combinations and chromatin status to form a
      spatially restricted pattern. We further demonstrate that changes in metabolism
      or temperature perturb the function of complex clusters. We show that the
      cooperative regulation between motifs around and within the cluster generates
      robust, class-specific OR expression. 

PMID- 25760345
TI  - Forecast model analysis for the morbidity of tuberculosis in Xinjiang, China.
AB  - Tuberculosis is a major global public health problem, which also affects economic
      and social development. China has the second largest burden of tuberculosis in
      the world. The tuberculosis morbidity in Xinjiang is much higher than the
      national situation; therefore, there is an urgent need for monitoring and
      predicting tuberculosis morbidity so as to make the control of tuberculosis more
      effective. Recently, the Box-Jenkins approach, specifically the autoregressive
      integrated moving average (ARIMA) model, is typically applied to predict the
      morbidity of infectious diseases; it can take into account changing trends,
      periodic changes, and random disturbances in time series. Autoregressive
      conditional heteroscedasticity (ARCH) models are the prevalent tools used to deal
      with time series heteroscedasticity. In this study, based on the data of the
      tuberculosis morbidity from January 2004 to June 2014 in Xinjiang, we establish
      the single ARIMA (1, 1, 2) (1, 1, 1)12 model and the combined ARIMA (1, 1, 2) (1,
      1, 1)12-ARCH (1) model, which can be used to predict the tuberculosis morbidity
      successfully in Xinjiang. Comparative analyses show that the combined model is
      more effective. To the best of our knowledge, this is the first study to
      establish the ARIMA model and ARIMA-ARCH model for prediction and monitoring the
      monthly morbidity of tuberculosis in Xinjiang. Based on the results of this
      study, the ARIMA (1, 1, 2) (1, 1, 1)12-ARCH (1) model is suggested to give
      tuberculosis surveillance by providing estimates on tuberculosis morbidity trends
      in Xinjiang, China. 

PMID- 25760347
TI  - Adiponectin in asthma: implications for phenotyping.
AB  - Asthma is a heterogeneous inflammatory airway disease, which exhibits multiple
      phenotypes, mainly defined by a combination of different clinical features.
      Asthma phenotypes include age at onset, smoking status, exacerbations frequency,
      and co-existence of obesity. Links between specific biological pathways and
      phenotypes are emerging. The genetic background together with detectable
      biomarkers could more accurately identify asthma phenotypes consistent with
      clinical-physiological characteristics and response to therapies. Several cross
      sectional studies indicate a strict correlation between adipose tissue, obesity,
      and asthma suggesting that obesity is not only a risk factor for asthma but also
      a predictor of poor prognosis. Despite the strong clinical correlation between
      obesity and asthma, the underlying biological pathways have not been extensively
      investigated. Recently, a pivotal role for adiponectin has been recognized in
      physio-pathological conditions of lung. Adiponectin is expressed as a 247
      residues long protein and secreted as oligomers of low, medium and high molecular
      weight. The larger oligomers seem to have a more pronounced insulinsensitizing,
      anti-atherogenic, and anti-inflammatory effects. Interestingly, the three
      receptors AdipoR1, AdipoR2, and Tcadherin mediating adiponectin activity are
      expressed on lung cells mediating adiponectin beneficial effects. Recently,
      different studies demonstrated the involvement of adiponectin in asthma since its
      levels and the expression of AdipoR1, AdipoR2 and T-cadherin are modulated in
      asthma patients and in asthma mouse models. In the present study, we review the
      literature reporting adiponectin impact on expression of specific clinical asthma
      phenotypes. 

PMID- 25760346
TI  - Antibiotic treatment of severe exacerbations of chronic obstructive pulmonary
      disease with procalcitonin: a randomized noninferiority trial.
AB  - BACKGROUND: The duration of antibiotic treatment of exacerbations of COPD (ECOPD)
      is controversial. Serum procalcitonin (PCT) is a biomarker of bacterial infection
      used to identify the cause of ECOPD. METHODS AND FINDINGS: We investigated
      whether a PCT-guided plan would allow a shorter duration of antibiotic treatment
      in patients with severe ECOPD. For this multicenter, randomized, non-inferiority
      trial, we enrolled 184 patients hospitalized with ECOPD from 18 hospitals in
      Italy. Patients were assigned to receive antibiotics for 10 days (standard group)
      or for either 3 or 10 days (PCT group). The primary outcome was the rate of ECOPD
      at 6 months. Having planned to recruit 400 patients, we randomized only 183: 93
      in the PCT group and 90 in the standard group. Thus, the completed study was
      underpowered. The ECOPD rate at 6 months between PCT-guided and standard
      antibiotic treatment was not significant (% difference, 4.04; 90% confidence
      interval [CI], -7.23 to 15.31), but the CI included the non-inferiority margin of
      15. In the PCT-guided group, about 50% of patients were treated for 3 days, and
      there was no difference in primary or secondary outcomes compared to patients
      treated for 10 days. CONCLUSIONS: Although the primary and secondary clinical
      outcomes were no different for patients treated for 3 or 10 days in the PCT
      group, the conclusion that antibiotics can be safely stopped after 3 days in
      patients with low serum PCT cannot be substantiated statistically. Thus, the
      results of this study are inconclusive regarding the noninferiority of the PCT
      guided plan compared to the standard antibiotic treatment. The study was funded
      by Agenzia Italiana del Farmaco (AIFA-FARM58J2XH). Clinical trial registered with
      www.clinicaltrials.gov (NCT01125098). TRIAL REGISTRATION: ClinicalTrials.gov
      NCT01125098.

PMID- 25760348
TI  - Devil declines and catastrophic cascades: is mesopredator release of feral cats
      inhibiting recovery of the eastern quoll?
AB  - The eastern quoll (Dasyurus viverrinus) is a medium-sized Australian marsupial
      carnivore that has recently undergone a rapid and severe population decline over
      the 10 years to 2009, with no sign of recovery. This decline has been linked to a
      period of unfavourable weather, but subsequent improved weather conditions have
      not been matched by quoll recovery. A recent study suggested another mechanism:
      that declines in Tasmanian devil (Sarcophilus harrisii) populations, due to the
      spread of the fatal Devil Facial Tumour Disease, have released feral cats (Felis
      catus) from competitive suppression, with eastern quoll declines linked to a
      subsequent increase in cat sightings. Yet current evidence of intraguild
      suppression among devils, cats and quolls is scant and equivocal. We therefore
      assessed the influences of top-down effects on abundance and activity patterns
      among devils, feral cats and eastern quolls. Between 2011 and 2013, we monitored
      four carnivore populations using longitudinal trapping and camera surveys, and
      performed camera surveys at 12 additional sites throughout the eastern quoll's
      range. We did not find evidence of a negative relationship between devil and cat
      abundance, nor of higher cat abundance in areas where devil populations had
      declined the longest. Cats did not appear to avoid devils spatially; however,
      there was evidence of temporal separation of cat and devil activity, with reduced
      separation and increasing nocturnal activity observed in areas where devils had
      declined the longest. Cats and quolls used the same areas, and there was no
      evidence that cat and quoll abundances were negatively related. Temporal overlap
      in observed cat and quoll activity was higher in summer than in winter, but this
      seasonal difference was unrelated to devil declines. We suggest that cats did not
      cause the recent quoll decline, but that predation of juvenile quolls by cats
      could be inhibiting low density quoll populations from recovering their former
      abundance through a 'predator pit' effect following weather-induced decline.
      Predation intensity could increase further should cats become increasingly
      nocturnal in response to devil declines. 

PMID- 25760351
TI  - Half-baked--the retail promotion of marijuana edibles.

PMID- 25760350
TI  - Antibodies against immature virions are not a discriminating factor for dengue
      disease severity.
AB  - Humoral immunity plays an important role in controlling dengue virus (DENV)
      infection. Antibodies (Abs) developed during primary infection protect against
      subsequent infection with the same dengue serotype, but can enhance disease
      following secondary infection with a heterologous serotype. A DENV virion has two
      surface proteins, envelope protein E and (pre)-membrane protein (pr)M, and
      inefficient cleavage of the prM protein during maturation of progeny virions
      leads to the secretion of immature and partially immature particles.
      Interestingly, we and others found that historically regarded non-infectious prM
      containing DENV particles can become highly infectious in the presence of E- and
      prM-Abs. Accordingly, we hypothesized that these virions contribute to the
      exacerbation of disease during secondary infection. Here, we tested this
      hypothesis and investigated the ability of acute sera of 30 DENV2-infected
      patients with different grades of disease severity, to bind, neutralize and/or
      enhance immature DENV2. We found that a significant fraction of serum Abs bind to
      the prM protein and to immature virions, but we observed no significant
      difference between the disease severity groups. Furthermore, functional analysis
      of the Abs did not underscore any specific correlation between the
      neutralizing/enhancing activity towards immature DENV2 and the development of
      more severe disease. Based on our analysis of acute sera, we conclude that Abs
      binding to immature virions are not a discriminating factor in dengue
      pathogenesis. 

PMID- 25760349
TI  - Vaccinia virus protein complex F12/E2 interacts with kinesin light chain isoform
      2 to engage the kinesin-1 motor complex.
AB  - During vaccinia virus morphogenesis, intracellular mature virus (IMV) particles
      are wrapped by a double lipid bilayer to form triple enveloped virions called
      intracellular enveloped virus (IEV). IEV are then transported to the cell surface
      where the outer IEV membrane fuses with the cell membrane to expose a double
      enveloped virion outside the cell. The F12, E2 and A36 proteins are involved in
      transport of IEVs to the cell surface. Deletion of the F12L or E2L genes causes a
      severe inhibition of IEV transport and a tiny plaque size. Deletion of the A36R
      gene leads to a smaller reduction in plaque size and less severe inhibition of
      IEV egress. The A36 protein is present in the outer membrane of IEVs, and over
      expressed fragments of this protein interact with kinesin light chain (KLC).
      However, no interaction of F12 or E2 with the kinesin complex has been reported
      hitherto. Here the F12/E2 complex is shown to associate with kinesin-1 through an
      interaction of E2 with the C-terminal tail of KLC isoform 2, which varies
      considerably between different KLC isoforms. siRNA-mediated knockdown of KLC
      isoform 1 increased IEV transport to the cell surface and virus plaque size,
      suggesting interaction with KLC isoform 1 is somehow inhibitory of IEV transport.
      In contrast, knockdown of KLC isoform 2 did not affect IEV egress or plaque
      formation, indicating redundancy in virion egress pathways. Lastly, the
      enhancement of plaque size resulting from loss of KLC isoform 1 was abrogated by
      removal of KLC isoforms 1 and 2 simultaneously. These observations suggest
      redundancy in the mechanisms used for IEV egress, with involvement of KLC
      isoforms 1 and 2, and provide evidence of interaction of F12/E2 complex with the
      kinesin-1 complex. 

PMID- 25760352
TI  - Medical marijuana's public health lessons--implications for retail marijuana in
      Colorado.

PMID- 25760353
TI  - The Watchman saga--closure at last?

PMID- 25760354
TI  - Liberal or restrictive transfusion after cardiac surgery.
AB  - BACKGROUND: Whether a restrictive threshold for hemoglobin level in red-cell
      transfusions, as compared with a liberal threshold, reduces postoperative
      morbidity and health care costs after cardiac surgery is uncertain. METHODS: We
      conducted a multicenter, parallel-group trial in which patients older than 16
      years of age who were undergoing nonemergency cardiac surgery were recruited from
      17 centers in the United Kingdom. Patients with a postoperative hemoglobin level
      of less than 9 g per deciliter were randomly assigned to a restrictive
      transfusion threshold (hemoglobin level <7.5 g per deciliter) or a liberal
      transfusion threshold (hemoglobin level <9 g per deciliter). The primary outcome
      was a serious infection (sepsis or wound infection) or an ischemic event
      (permanent stroke [confirmation on brain imaging and deficit in motor, sensory,
      or coordination functions], myocardial infarction, infarction of the gut, or
      acute kidney injury) within 3 months after randomization. Health care costs,
      excluding the index surgery, were estimated from the day of surgery to 3 months
      after surgery. RESULTS: A total of 2007 patients underwent randomization; 4
      participants withdrew, leaving 1000 in the restrictive-threshold group and 1003
      in the liberal-threshold group. Transfusion rates after randomization were 53.4%
      and 92.2% in the two groups, respectively. The primary outcome occurred in 35.1%
      of the patients in the restrictive-threshold group and 33.0% of the patients in
      the liberal-threshold group (odds ratio, 1.11; 95% confidence interval [CI], 0.91
      to 1.34; P=0.30); there was no indication of heterogeneity according to subgroup.
      There were more deaths in the restrictive-threshold group than in the liberal
      threshold group (4.2% vs. 2.6%; hazard ratio, 1.64; 95% CI, 1.00 to 2.67;
      P=0.045). Serious postoperative complications, excluding primary-outcome events,
      occurred in 35.7% of participants in the restrictive-threshold group and 34.2% of
      participants in the liberal-threshold group. Total costs did not differ
      significantly between the groups. CONCLUSIONS: A restrictive transfusion
      threshold after cardiac surgery was not superior to a liberal threshold with
      respect to morbidity or health care costs. (Funded by the National Institute for
      Health Research Health Technology Assessment program; Current Controlled Trials
      number, ISRCTN70923932.).

PMID- 25760355
TI  - Compliance with results reporting at ClinicalTrials.gov.
AB  - BACKGROUND: The Food and Drug Administration Amendments Act (FDAAA) mandates
      timely reporting of results of applicable clinical trials to ClinicalTrials.gov.
      We characterized the proportion of applicable clinical trials with publicly
      available results and determined independent factors associated with the
      reporting of results. METHODS: Using an algorithm based on input from the
      National Library of Medicine, we identified trials that were likely to be subject
      to FDAAA provisions (highly likely applicable clinical trials, or HLACTs) from
      2008 through 2013. We determined the proportion of HLACTs that reported results
      within the 12-month interval mandated by the FDAAA or at any time during the 5
      year study period. We used regression models to examine characteristics
      associated with reporting at 12 months and throughout the 5-year study period.
      RESULTS: From all the trials at ClinicalTrials.gov, we identified 13,327 HLACTs
      that were terminated or completed from January 1, 2008, through August 31, 2012.
      Of these trials, 77.4% were classified as drug trials. A total of 36.9% of the
      trials were phase 2 studies, and 23.4% were phase 3 studies; 65.6% were funded by
      industry. Only 13.4% of trials reported summary results within 12 months after
      trial completion, whereas 38.3% reported results at any time up to September 27,
      2013. Timely reporting was independently associated with factors such as FDA
      oversight, a later trial phase, and industry funding. A sample review suggested
      that 45% of industry-funded trials were not required to report results, as
      compared with 6% of trials funded by the National Institutes of Health (NIH) and
      9% of trials that were funded by other government or academic institutions.
      CONCLUSIONS: Despite ethical and legal obligations to disclose findings promptly,
      most HLACTs did not report results to ClinicalTrials.gov in a timely fashion
      during the study period. Industry-funded trials adhered to legal obligations more
      often than did trials funded by the NIH or other government or academic
      institutions. (Funded by the Clinical Trials Transformation Initiative and the
      NIH.).

PMID- 25760356
TI  - Viscosupplementation for osteoarthritis of the knee.

PMID- 25760357
TI  - Sterile pyuria.

PMID- 25760358
TI  - Images in clinical medicine. Penile fracture.

PMID- 25760359
TI  - Case records of the Massachusetts General Hospital. Case 8-2015. A 68-year-old
      man with multiple myeloma, skin tightness, arthralgias, and edema.

PMID- 25760360
TI  - "TITRe"ing the approach to transfusions after cardiac surgery.

PMID- 25760361
TI  - Clonal hematopoiesis and blood-cancer risk.

PMID- 25760362
TI  - Clonal hematopoiesis and blood-cancer risk.

PMID- 25760363
TI  - Cytisine versus nicotine for smoking cessation.

PMID- 25760364
TI  - Thrombospondin type-1 domain-containing 7A in idiopathic membranous nephropathy.

PMID- 25760365
TI  - Thrombospondin type-1 domain-containing 7A in idiopathic membranous nephropathy.

PMID- 25760366
TI  - Lactic acidosis.

PMID- 25760367
TI  - Lactic acidosis.

PMID- 25760368
TI  - Lactic acidosis.

PMID- 25760369
TI  - Lactic acidosis.

PMID- 25760370
TI  - Lactic acidosis.

PMID- 25760371
TI  - Lactic acidosis.

PMID- 25760372
TI  - Two cases of heart failure after implantation of a CoreValve prosthesis.

PMID- 25760373
TI  - Two cases of heart failure after implantation of a CoreValve prosthesis.

PMID- 25760374
TI  - Images in clinical medicine. Passage of a sialolith.

PMID- 25760375
TI  - Enhanced Osteogenic Behavior of ADSCs Produced by Deproteinized Antler Cancellous
      Bone and Evidence for Involvement of ERK Signaling Pathway.
AB  - Calcinated antler cancellous bone (CACB) is useful in repair of bone defects, as
      its composition and architecture is analogous to natural extracellular bone
      matrix. The use of CACB scaffolds with adipose-derived stem cells (ADSCs) in
      repair of rabbit mandibular bone defects was investigated along with the
      underlying molecular signaling pathways involved. CACB promoted the adhesion,
      spreading, and viability of ADSCs. Increased extracellular matrix production and
      expression of osteogenic markers in ADSCs were observed when seeded in CACB. The
      temporal kinetics of mRNA expression of ADSCs cultured in CACB lagged in
      comparison with that observed in cells grown in medium with osteogenic
      supplements. Activation of the extracellular signal-related kinases (ERK) 1/2 and
      RUNX-2 in CACB-cultured ADSCs was observed, and this activation was attenuated by
      the MeK inhibitor U0126. Microcomputed tomography scanning analysis and
      histological evaluations showed that loading the CACB with ADSCs resulted in
      enhanced new bone formation and angiogenesis when the composites were implanted
      in rabbit mandibular defects. These results indicated that the osteogenic
      behavior of ADSCs might be driven by the microenvironment formed by CACB via the
      ERK signaling pathway. These CACB/ADSCs composites have promising therapeutic
      potential for large bone defect repairs. 

PMID- 25760376
TI  - RNA-dependent RNA polymerase (NIb) of the potyviruses is an avirulence factor for
      the broad-spectrum resistance gene Pvr4 in Capsicum annuum cv. CM334.
AB  - Potyviruses are one of the most destructive viral pathogens of Solanaceae plants.
      In Capsicum annuum landrace CM334, a broad-spectrum gene, Pvr4 is known to be
      involved in resistance against multiple potyviruses, including Pepper mottle
      virus (PepMoV), Pepper severe mosaic virus (PepSMV), and Potato virus Y (PVY).
      However, a potyvirus avirulence factor against Pvr4 has not been identified. To
      identify the avirulence factor corresponding to Pvr4 in potyviruses, we performed
      Agrobacterium-mediated transient expressions of potyvirus protein coding regions
      in potyvirus-resistant (Pvr4) and -susceptible (pvr4) pepper plants.
      Hypersensitive response (HR) was observed only when a RNA-dependent RNA
      polymerase (NIb) of PepMoV, PepSMV, or PVY was expressed in Pvr4-bearing pepper
      leaves in a genotype-specific manner. In contrast, HR was not observed when the
      NIb of Tobacco etch virus (TEV), a virulent potyvirus, was expressed in Pvr4
      bearing pepper leaves. Our results clearly demonstrate that NIbs of PepMoV,
      PepSMV, and PVY serve as avirulence factors for Pvr4 in pepper plants. 

PMID- 25760377
TI  - Black-tailed prairie dogs, cattle, and the conservation of North America's arid
      grasslands.
AB  - Prairie dogs (Cynomys spp.) have been eliminated from over 95% of their historic
      range in large part from direct eradication campaigns to reduce their purported
      competition with cattle for forage. Despite the longstanding importance of this
      issue to grassland management and conservation, the ecological interactions
      between cattle and prairie dogs have not been well examined. We address this
      issue through two complementary experiments to determine if cattle and prairie
      dogs form a mutualistic grazing association similar to that between prairie dogs
      and American bison. Our experimental results show that cattle preferentially
      graze along prairie dog colony edges and use their colony centers for resting,
      resembling the mutualistic relationship prairie dogs have with American bison.
      Our results also show that prairie dog colonies are not only an important
      component of the grassland mosaic for maintaining biodiversity, but also provide
      benefits to cattle, thereby challenging the long-standing view of prairie dogs as
      an undesirable pest species in grasslands. 

PMID- 25760379
TI  - Angiotensin II promotes melanogenesis via angiotensin II type 1 receptors in
      human melanocytes.
AB  - Angiotensin II (AngII) is a hormone with long-established cardiovascular actions.
      Previous studies have revealed an additional role for AngII in the regulation of
      cutaneous wound healing. To evaluate the association between AngII and abnormal
      pigmentation of cutaneous wound healing, the present study used human melanocytes
      to investigate the effects of AngII on melanogenesis, and to elucidate the
      possible underlying mechanisms. Primary culture melanocytes were treated with
      AngII either alone or in combination with an AngII type 1 (AT1) receptor
      antagonist, losartan (LOS). The melanin content and tyrosinase activity were
      measured and reverse transcription-quantitative polymerase chain reaction (RT
      qPCR) and western blotting were performed to assess the proteins involved in
      melanogenesis and the AT1 receptor. AngII regulated the mRNA expression of AT1 in
      the melanocytes. The melanin content and tyrosinase activity increased in
      response to treatment with AngII in a concentration-dependent manner. RT-qPCR and
      western blotting revealed that the AT1 receptor antagonist, LOS, eliminated this
      effect. These results provide a novel insight into the role of AngII and its
      associated signaling in melanogenesis.

PMID- 25760378
TI  - Transcriptome analysis reveals that Mullerian inhibiting substance regulates
      signaling pathways that contribute to endometrial carcinogenesis.
AB  - Mullerian inhibiting substance (MIS) has been shown to inhibit growth of a number
      of tumors in vitro and/or in vivo, but the downstream pathways which it regulates
      are not fully understood. In the present study we show that MIS type II receptor
      was highly expressed in AN3CA cells, a cell line derived from human endometrial
      cancer cell in which MIS-treatment caused a reduction of cell viability, and
      induced cellular apoptosis and genes involved cell cycle arrest. To understand
      the genome-wide effects of MIS on gene regulation, we performed serial gene
      expression analyses from 0 to 96 h at 24 h intervals after treating AN3CA cells
      with MIS. Transcriptomic analysis of molecular changes induced by MIS identified
      2,688 differentially expressed genes that were significantly up- or down
      regulated during the 96 h study period. When the 2,688 differentially expressed
      genes were mapped to known biological processes, Wnt-, cancer-, proteolysis-,
      cytoskeleton-, cell cycle-, apoptosis-, and MAPK-signaling pathways emerged as
      the functions most significantly changed by MIS in AN3CA cells. Furthermore,
      western blot analysis validated that protein expression of cell cycle inhibitory
      genes, apoptotic protease activating factor-1 (APAF-1), beta-catenin-interacting
      protein (ICAT), Rb related protein 130 (p130), and inhibitor of disheveled Dvl
      and Axin complex (IDAX), were gradually increased over the time of the study,
      whereas downstream cell cycle activating genes, cyclin-dependent kinase 2 (CDK2)
      and phospho-c-Jun were downregulated in MIS-treated AN3CA cells. These
      transcriptome analyses support previous observations that MIS functions as a
      tumor suppressor, potentially by regulating signaling pathways that could
      contribute to endometrial carcinogenesis, and indicating that MIS should be
      considered as a potential treatment for endometrial cancer.

PMID- 25760380
TI  - Nonlinear quantum optics in the (ultra)strong light-matter coupling.
AB  - The propagation of N photons in one dimensional waveguides coupled to M qubits is
      discussed, both in the strong and ultrastrong qubit-waveguide coupling. Special
      emphasis is placed on the characterisation of the nonlinear response and its
      linear limit for the scattered photons as a function of N, M, qubit inter
      distance and light-matter coupling. The quantum evolution is numerically solved
      via the matrix product states technique. The time evolutions for both the field
      and qubits are computed. The nonlinear character (as a function of N/M) depends
      on the computed observable. While perfect reflection is obtained for N/M?1,
      photon-photon correlations are still resolved for ratios N/M=non-zero. Inter
      qubit distance enhances the nonlinear response. Moving to the ultrastrong
      coupling regime, we observe that inelastic processes are robust against the
      number of qubits and that the qubit-qubit interaction mediated by the photons is
      qualitatively modified. The theory developed in this work models experiments in
      circuit QED, photonic crystals and dielectric waveguides.

PMID- 25760381
TI  - A wider pelvis does not increase locomotor cost in humans, with implications for
      the evolution of childbirth.
AB  - The shape of the human female pelvis is thought to reflect an evolutionary trade
      off between two competing demands: a pelvis wide enough to permit the birth of
      large-brained infants, and narrow enough for efficient bipedal locomotion. This
      trade-off, known as the obstetrical dilemma, is invoked to explain the relative
      difficulty of human childbirth and differences in locomotor performance between
      men and women. The basis for the obstetrical dilemma is a standard static
      biomechanical model that predicts wider pelves in females increase the metabolic
      cost of locomotion by decreasing the effective mechanical advantage of the hip
      abductor muscles for pelvic stabilization during the single-leg support phase of
      walking and running, requiring these muscles to produce more force. Here we
      experimentally test this model against a more accurate dynamic model of hip
      abductor mechanics in men and women. The results show that pelvic width does not
      predict hip abductor mechanics or locomotor cost in either women or men, and that
      women and men are equally efficient at both walking and running. Since a wider
      birth canal does not increase a woman's locomotor cost, and because selection for
      successful birthing must be strong, other factors affecting maternal pelvic and
      fetal size should be investigated in order to help explain the prevalence of
      birth complications caused by a neonate too large to fit through the birth canal.

PMID- 25760382
TI  - Anti-hyperuricemic and nephroprotective effects of rhein in hyperuricemic mice.
AB  - Hyperuricemia has been considered to be a key risk factor for kidney disease. The
      formation of uric acid crystals in the kidney further stimulates an intensive
      inflammatory response. Rhein possesses various pharmacological activities,
      including anti-inflammatory, antioxidative, antitumor, purgative effects, and so
      on. To our knowledge, no previous work has been reported about the therapeutic
      effect of rhein on urate nephropathy. In this study, a model of hyperuricemia and
      nephropathy induced by adenine and ethambutol in mice was established. Meanwhile,
      the potential beneficial effects and mechanisms of rhein on hyperuricemia and
      nephropathy were also investigated. The results demonstrated that rhein
      significantly decreased the serum uric acid level by inhibiting the xanthine
      oxidase activity and increasing the excretion of urinary uric acid. In addition,
      rhein also markedly improved kidney damage related to hyperuricemia. Further
      investigation indicated that rhein improved the symptoms of nephropathy through
      decreasing the production of proinflammatory cytokines, including interleukin
      1beta, prostaglandin E2, and tumor necrosis factor-alpha and inhibiting the
      expression of transforming growth factor-beta1. The present study suggests that
      rhein may have a considerable potential for development as an anti-hyperuricemic
      and nephroprotective agent for clinical application. 

PMID- 25760383
TI  - Meroterpenoids and a naphthoquinone from Arnebia euchroma and their cytotoxic
      activity.
AB  - Four new meroterpenoids, arnebinols A-D (1-4), and one new prenylated
      naphthoquinone, 5,8-O-dimethyl-11-deoxyalkannin (5), together with seven known
      meroterpenoids (6-12) were isolated from the roots of Arnebia euchroma. The
      structures of the isolated compounds were elucidated unambiguously by
      spectroscopic data analysis, as well as X-ray-single crystal diffraction
      analysis. Arnebinol A (1) and B (2) are rare meroterpenoids possessing a 6/10/5
      tricyclic ring system. Compounds 1-12 were evaluated for their cytotoxicities
      against MG-63 and SNU387 human cancer cell lines. Compound 5 exhibited the most
      potent activity with IC50 values of 2.69 uM and 6.08 uM, respectively. 

PMID- 25760384
TI  - The antigluconeogenic activity of cucurbitacins from Momordica charantia.
AB  - Five new cucurbitacins, kuguacins II-VI (1-5), along with five known analogues (6
      10), were obtained from the fruit of Momordica charantia. Structures of the new
      compounds were elucidated as 5beta,19-epoxycucurbit-23-en-7-on-3beta,25-diol (1),
      5beta,19-epoxycucurbit-7,23-dion-3beta,25-diol (2), 5beta,19-epoxycucurbit-6-en
      19,23-dion-3beta,25-diol (3), 5beta,19-epoxy-23,24,25,26,27-pentanorcucurbit-6-en
      7,19-dion-3beta,22-diol (4), and cucurbit-5-en-7,23-dion-3beta,19,25-triol (5) by
      extensive spectroscopic and single-crystal X-ray diffraction analyses. Some
      cucurbitane compounds from this species were screened for their potential
      antidiabetic properties in terms of antigluconeogenic activity. As a result,
      compounds 1, 10, 11, and 12 (at 25-100 uM) showed concentration-dependent
      inhibition on glucose production from liver cells. In addition, compounds 11 and
      12 (at 100 uM) showed around 20-30 % inhibition on PEPCK activity. 

PMID- 25760385
TI  - Metabolite profiling of tissues of Acorus calamus and Acorus tatarinowii rhizomes
      by using LMD, UHPLC-QTOF MS, and GC-MS.
AB  - Acorus calamus and its related species are of significant importance to the food
      and fragrance industries due to their varied applications. They are also a cause
      of critical concern due to their toxic beta-asarone content. Several toxicity
      cases have occurred due to high beta-asarone compositions in food products.
      Hence, limits for their use are strictly regulated by the Food and Drug
      Administration, the European Union, and legislations of different countries. The
      identification of species with a lower beta-asarone content is of great
      significance. In this report, the metabolite profiles and essential oil content
      of A. calamus and Acorus tatarinowii rhizomes were analysed and compared using
      UHPLC-QTOF-MS and GC-MS techniques. The metabolite profiles were similar;
      however, beta-asarone content was higher in A. calamus rhizomes. The developed
      methods can be applied for microscopic and macroscopic identification, and
      quality control of food products containing beta-asarone. 

PMID- 25760386
TI  - Solvent-dependent structure of molecular iodine probed by picosecond X-ray
      solution scattering.
AB  - The effect of solute-solvent interaction on molecular structure and reaction
      dynamics has been a target of intense studies in solution-phase chemistry, but it
      is often challenging to characterize the subtle effect of solute-solvent
      interaction even for the simplest diatomic molecules. Since the I2 molecule has
      only one structural parameter and exhibits solvatochromism, it is a good model
      system for investigating the solvent dependence of the solute structure. By using
      X-rays as a probe, time-resolved X-ray liquidography (TRXL) can directly
      elucidate the structures of reacting molecules in solution and can thus determine
      the solvent-dependent structural change with atomic resolution. Here, by applying
      TRXL, we characterized the molecular structure of I2 in methanol and cyclohexane
      with sub-angstrom accuracy. Specifically, we found that the I-I bond length of I2
      is longer in the polar solvent (methanol) by ~0.2 A than in nonpolar solvents
      (cyclohexane and CCl4). Density functional theory (DFT) using 22 explicit
      methanol molecules well reproduces the longer I-I bond of molecular iodine in
      methanol and reveals that the larger bond length originates from partial negative
      charge filled in an antibonding sigma* orbital through solvent-to-solute charge
      transfer. 

PMID- 25760388
TI  - Erythematous Papules and Vesicles on the Palms, Soles, and Oropharynx.

PMID- 25760389
TI  - A Clinical Trial with Brazilian Arnica (Solidago chilensis Meyen) Glycolic
      Extract in the Treatment of Tendonitis of Flexor and Extensor Tendons of Wrist
      and Hand.
AB  - One of the Brazilian arnicas, Solidago chilensis Meyen, is a species of the
      Asteraceae family. This plant is known by this common name because it shares
      remarkably similar organoleptic properties with the genus Arnica L., also within
      the family Asteraceae. We examined the effectiveness of the S. chilensis fluid
      extract used externally for treating tendinitis of flexor and extensor tendons of
      wrist and hand in placebo-controlled double-blind clinical pharmacological
      studies. This study was approved by the Ethical Committee for Scientific Research
      in Human Beings at University Vila Velha-UVV. Two daily skin applications on the
      arm skin of a gel cream containing a 5% glycolic plant extract were administered
      to eight volunteers for 21 days. Among the volunteers, one of their arms was used
      as the placebo group, and the other one was used as a test group. Statistical
      data analyses demonstrated a significant reduction in the perception of pain in
      the arms in the test group, when it was compared to those receiving only the
      placebo.

PMID- 25760390
TI  - Electrocatalytic water oxidation by Cu(II) complexes with branched peptides.
AB  - Two mononuclear Cu(II) complexes with tetrapeptides incorporating a L-2,3
      diaminopropionic acid (dap) branching unit are reported to undergo PCET and
      catalyse water oxidation. C-terminal His extension of dap (L = 2GH) instead of
      Gly (L = 3G) lowers the pKa for Cu(III)H-2L (9.36 vs. 9.98) and improves the TOF
      at pH 11 (53 vs. 24 s(-1)).

PMID- 25760387
TI  - microRNA-449a functions as a tumor suppressor in neuroblastoma through inducing
      cell differentiation and cell cycle arrest.
AB  - microRNA-449a (miR-449a) has been identified to function as a tumor suppressor in
      several types of cancers. However, the role of miR-449a in neuroblastoma has not
      been intensively investigated. We recently found that the overexpression of miR
      449a significantly induces neuroblastoma cell differentiation, suggesting its
      potential tumor suppressor function in neuroblastoma. In this study, we further
      investigated the mechanisms underlying the tumor suppressive function of miR-449a
      in neuroblastoma. We observed that miR-449a inhibits neuroblastoma cell survival
      and growth through 2 mechanisms--inducing cell differentiation and cell cycle
      arrest. Our comprehensive investigations on the dissection of the target genes of
      miR-449a revealed that 3 novel targets- MFAP4, PKP4 and TSEN15 -play important
      roles in mediating its differentiation-inducing function. In addition, we further
      found that its function in inducing cell cycle arrest involves down-regulating
      its direct targets CDK6 and LEF1. To determine the clinical significance of the
      miR-449a-mediated tumor suppressive mechanism, we examined the correlation
      between the expression of these 5 target genes in neuroblastoma tumor specimens
      and the survival of neuroblastoma patients. Remarkably, we noted that high tumor
      expression levels of all the 3 miR-449a target genes involved in regulating cell
      differentiation, but not the target genes involved in regulating cell cycle, are
      significantly correlated with poor survival of neuroblastoma patients. These
      results suggest the critical role of the differentiation-inducing function of miR
      449a in determining neuroblastoma progression. Overall, our study provides the
      first comprehensive characterization of the tumor-suppressive function of miR
      449a in neuroblastoma, and reveals the potential clinical significance of the miR
      449a-mediated tumor suppressive pathway in neuroblastoma prognosis.

PMID- 25760391
TI  - Correlates of Licensed and Unlicensed Nurse Staffing Levels on Inpatient
      Psychiatric Units.
AB  - Nurse staffing on inpatient psychiatric units was examined using data from a
      national sample of 409 hospitals. Hospitals' nonpsychiatric unit staffing
      predicted psychiatric unit staffing, accounting for 15.2% and 6.8% of variability
      in licensed and unlicensed staffing, respectively. Licensed and unlicensed
      staffing on psychiatric units were inversely related. Of the non-California
      hospitals in the study, 70% had annual levels of psychiatric unit staffing
      exceeding California's mandated 1:6 licensed staffing ratio. 

PMID- 25760393
TI  - An Evidence-Based Systematic Review on the Diagnostic Accuracy of Hearing
      Screening Instruments for Preschool- and School-Age Children.
AB  - PURPOSE: The purpose of this article is to conduct an evidence-based systematic
      review on the accuracy of pure-tone or otoacoustic emission (OAE) screening for
      identifying hearing loss in preschool- and school-age children. METHOD: A
      systematic search of the literature published between 1975 and 2013 was
      conducted. Articles meeting the selection criteria were critically appraised for
      quality. Selection criteria required that behavioral thresholds be measured in
      children failing the screen and in at least a subset of children passing the
      screen. Sensitivity and specificity were used to calculate positive and negative
      likelihood ratios that could be compared between instruments. RESULTS: Eighteen
      studies were included in the final analysis. There was considerable variability
      among studies on stimulus levels, response criteria, and definition of hearing
      loss. Approximately half of positive and negative likelihood ratio pairs for OAEs
      (52%) and pure-tone screening (45%) were considered suggestive or informative for
      identifying hearing loss. CONCLUSIONS: Both pure-tone and OAE screening can
      identify hearing loss in preschool- and school-age children. Studies that
      compared both tools in the same population concluded that pure-tone screening had
      higher sensitivity than OAE screening and thus was considered the preferred tool.
      Future research should incorporate standard stimulus levels, response criteria,
      and definitions of hearing loss.

PMID- 25760392
TI  - Can Brown Fat Win the Battle Against White Fat?
AB  - A rapid growth in the overweight and obese population in the last few decades
      suggest that the current diet, exercise, awareness or drug strategies are still
      not effectively restraining the obesity epidemic. Obesity results from increased
      energy intake, and the body's energy balance shifts towards energy abundance.
      Therefore, current research is focused on developing new strategies aimed at
      increasing energy expenditure. As a result, brown adipose tissue (BAT) is
      receiving tremendous attention since the major function of BAT is to dissipate
      energy as heat. For example, mouse models that have increased BAT activity or
      increased numbers of brown-like adipocytes within the white adipose tissue (WAT)
      are lean and protected from obesity. Alternatively, mouse models that lack BAT
      activity are more susceptible to age and diet-induced obesity. However, a
      significant loss of BAT mass during the natural growth process in humans has
      created enormous challenges in effectively utilizing this tissue to increase
      energy expenditure. New strategies are primarily focused on expanding the BAT
      mass and/or activating the existing BAT. In this regard, recent finding that
      expression of early B cell factor-2 (Ebf2) reprograms the white pre-adipocytes
      into brown adipocytes is a significant break-through in developing BAT-mediated
      strategies to treat obesity. Here we review the major biological functions of WAT
      and BAT, which play critical but opposing roles in the energy spectrum, energy
      storage versus energy expenditure, and we evaluate whether activation and/or
      expansion of BAT is practically achievable to treat obesity in humans.

PMID- 25760395
TI  - Structures, electronic properties and stability phase diagrams for copper(I/II)
      bromide surfaces.
AB  - This study presents a comprehensive periodic slab DFT investigation into
      structures, electronic properties and thermodynamic stability of all plausible
      terminations of CuBr and CuBr2 surfaces. We first estimate lattice constants,
      formation and cohesive energies for the two bulk copper bromides before
      proceeding to analyse geometrical and electronic features of CuBr and CuBr2
      configurations. Surface geometries exhibit, to a large extent, corresponding bulk
      structures. Nevertheless, certain CuBr2 surfaces experience a downward
      displacement of the topmost Cu-containing layers. We plot total and projected
      density of states for bulk and surface geometries of these two copper bromides
      and calculate their associated Bader's electronic charges. Electronic structure
      analysis for the bulk and surfaces of these two copper bromides show that CuBr
      bulk and its most stable surface (CuBr(001)_Br) do not exhibit any metallic
      character, whereas CuBr2 bulk and its most stable surface (CuBr2(001)_Br) both
      exhibit metallic characters. The formalism of the ab initio atomistic
      thermodynamics affords the construction of energy phase diagrams. We predict that
      the CuBr(001) surface, truncated with Br atoms, is the most stable structure
      among the considered CuBr slabs at all physically meaningful ranges of the
      chemical potential of bromine. This surface resembles a c(2 * 2)-bromine sheet
      that was characterised experimentally from initial interaction of Br2 with a
      Cu(100) surface. We find that surfaces terminated with the electronegative
      bromine atoms, if accompanied by significant relaxation, tend to be more stable.
      Calculated surface energies predict the shapes of CuBr and CuBr2 nanoparticles as
      the chemical potential of bromine changes. 

PMID- 25760394
TI  - All-trans retinoic acid impairs the vasculogenic mimicry formation ability of U87
      stem-like cells through promoting differentiation.
AB  - The poor therapeutic effect of traditional antiangiogenic therapy on glioblastoma
      multiforme (GBM) may be attributed to vasculogenic mimicry (VM), which was
      previously reported to be promoted by cancer stem-like cells (SLCs). All-trans
      retinoic acid (ATRA), a potent reagent which drives differentiation, was reported
      to be able to eradicate cancer SLCs in certain malignancies. The aim of the
      present study was to investigate the effects of ATRA on the VM formation ability
      of U87 glioblastoma SLCs. The expression of cancer SLC markers CD133 and nestin
      was detected using immunocytochemistry in order to identify U87 SLCs. In
      addition, the differentiation of these SLCs was observed through detecting the
      expression of glial fibrillary acidic protein (GFAP), beta-tubulin III and
      galactosylceramidase (Galc) using immunofluorescent staining. The results showed
      that the expression levels of GFAP, beta-tubulin III and Galc were upregulated
      following treatment with ATRA in a dose-dependent manner. Furthermore, ATRA
      significantly reduced the proliferation, invasiveness, tube formation and
      vascular endothelial growth factor (VEGF) secretion of U87 SLCs. In conclusion,
      the VM formation ability of SLCs was found to be negatively correlated with
      differentiation. These results therefore suggested that ATRA may serve as a
      promising novel agent for the treatment of GBM due to its role in reducing VM
      formation.

PMID- 25760396
TI  - Orostachys japonicus inhibits the expression of MMP-2 and MMP-9 mRNA and
      modulates the expression of iNOS and COX-2 genes in human PMA-differentiated THP
      1 cells via inhibition of NF-kappaB and MAPK activation.
AB  - Orostachys japonicus has been used in traditional medicine as an anticancer
      agent. The present study aimed to investigate the mechanism by which O. japonicus
      extract affects the expression of matrix metalloproteinase (MMP)-2 and MMP-9, its
      association with the expression of the inducible nitric oxide synthase (iNOS) and
      cyclooxygenase-2 (COX-2) genes in phorbol myristate acetate-differentiated THP-1
      human monocytic leukemia cells and how it mediates the nuclear factor (NF)-kappaB
      and mitogen-activated protein kinase (MAPK) pathways. Cell proliferation was
      analyzed by MTT assay, mRNA expression was detected by quantitative polymerase
      chain reaction and protein expression was measured by western blot analysis. It
      was demonstrated that O. japonicus suppressed the mRNA expression of MMP-2 and
      MMP-9. In addition, O. japonicus was found to downregulate iNOS and COX-2
      transcription and translocation. Furthermore, O. japonicus inhibited NF-kappaB
      p65 activity as well as the phosphorylation of p38 MAPK, MAPK kinase (MEK) and
      extracellular signal regulated kinase (ERK). The present results suggested that
      O. japonicus inhibited not only MMP-2 and MMP-9 mRNA expression, but also iNOS
      and COX-2 gene expression, suppressed NF-kappaB activation and reduced
      phosphorylation of p38 MAPK, MEK and ERK. The present results therefore indicated
      that O. japonicus was able to inhibit the expression of MMP-2 and MMP-9 and
      suppress the transcription and translocation of iNOS and COX-2 by directly
      inhibiting the activation of NF-kappaB and the phosphorylation of the MAPK
      pathway in THP-1 cells.

PMID- 25760398
TI  - Transcriptional dynamics of homeobox C11 gene in water buffalo bubalus bubalis.
AB  - The Hox complex contains 39 genes clustered into four groups involved in cell
      differentiation and development. We cloned full-length sequence of Hoxc11 gene
      from water buffalo Bubalus bubalis, assessed its copy number, localized the same
      onto the chromosome 5, and studied its evolutionary conservation across the
      species. Northern hybridization of Hoxc11 showed a 2.2 kb band in the tissues
      analyzed. Real-Time PCR showed highest expression of Hoxc11 gene in lung followed
      by spleen, spermatozoa, and testis. Six interacting partners of this gene showed
      higher expression in spleen, lung, testis, and spermatozoa. During the early
      stages of development, Hoxc11 and its interacting partners both showed lower
      expression, which then became prominent during the age of 1-3 years, regressed
      drastically thereafter, and remained so until the animal's life time (~ 20
      years). The high expression of Hoxc11 and its interacting partners in spermatozoa
      and testis during the onset of puberty suggests its likely role in the
      differentiation of gonads and subsequent reproductive activities. Additional work
      on Hoxc11 especially, in the context of respiratory, immunological, and
      in/fertility in other species, including humans would be useful for establishing
      its broader biological significance towards the enrichment of functional and
      comparative genomics.

PMID- 25760399
TI  - Investigation of electron density changes at the onset of a chemical reaction
      using the state-specific dual descriptor from conceptual density functional
      theory.
AB  - The electron density changes from reactants towards the transition state of a
      chemical reaction is expressed as a linear combination of the state-specific dual
      descriptors (SSDD) of the corresponding reactant complexes. Consequently, the
      SSDD can be expected to bear important resemblance to the so-called natural
      orbitals for chemical valence (NOCV), introduced as the orbitals that diagonalize
      the deformation density matrix of interacting molecules. This agreement is shown
      for three case studies: the complexation of a Lewis acid with a Lewis base, a SN2
      nucleophilic substitution reaction and a Diels-Alder cycloaddition reaction. As
      such, the SSDD computed for reactant complexes are shown to provide important
      information about charge transfer interactions during a chemical reaction. 

PMID- 25760400
TI  - The importance of mental pain and physical dissociation in youth suicidality.
AB  - This study examines the importance of two suicide risk factors, mental pain and
      physical dissociation, among young people. Participants were 42 suicidal
      inpatients, 36 nonsuicidal inpatients, and 45 nonclinical participants. Overall,
      suicide attempters reported a stronger intensity of and lower tolerance for
      mental pain and more physical dissociation compared to the other two groups.
      Suicide attempters with a low tolerance for mental pain showed a higher level of
      dissociation from pain and insensitivity to bodily cues compared to nonsuicidal
      inpatients with similar levels of tolerance for mental pain. Physical
      dissociation contributed significantly to the likelihood of suicidality beyond
      the contribution of mental pain. Our results accentuate the importance of the
      combination of mental pain and physical dissociation in suicidality. Further
      research on the applicability of our findings to self-injurious behavior is
      warranted. 

PMID- 25760401
TI  - Effect of local chain dynamics on a bioinert interface.
AB  - Although many kinds of synthetic polymers have been investigated to construct
      blood-compatible materials, only a few have achieved success. To establish
      molecular designs for blood-compatible polymers, the chain structure and dynamics
      at the water interface must be understood using solid evidence as the first bench
      mark. Here we show that polymer dynamics at the water interface impacts on
      structure of the interfacial water, resulting in a change in protein adsorption
      and of platelet adhesion. As a particular material, a blend composed of poly(2
      methoxyethyl acrylate) (PMEA) and poly(methyl methacrylate) was used. PMEA was
      segregated to the water interface. While the local conformation of PMEA at the
      water interface was insensitive to its molecular weight, the local dynamics
      became faster with decreasing molecular weight, resulting in a disturbance of the
      network structure of waters at the interface. This leads to the extreme
      suppression of protein adsorption and platelet adhesion. 

PMID- 25760402
TI  - Divalent transition-metal-ion stress induces prodigiosin biosynthesis in
      Streptomyces coelicolor M145: formation of coeligiosins.
AB  - The bacterium Streptomyces coelicolor M145 reacts to transition-metal-ion stress
      with myriad growth responses, leading to different phenotypes. In particular, in
      the presence of Co(2+) ions (0.7 mM) S. coelicolor consistently produced a red
      phenotype. This phenotype, when compared to the wild type, differed strongly in
      its production of volatile compounds as well as high molecular weight secondary
      metabolites. LC-MS analysis revealed that in the red phenotype the production of
      the prodigiosins, undecylprodigiosin and streptorubin B, was strongly induced
      and, in addition, several intense signals appeared in the LC-MS chromatogram.
      Using LC-MS/MS and NMR spectroscopy, two new prodigiosin derivatives were
      identified, that is, coeligiosin A and B, which contained an additional
      undecylpyrrolyl side chain attached to the central carbon of the tripyrrole ring
      system of undecylprodigiosin or streptorubin B. This example demonstrates that
      environmental factors such as heavy metal ion stress can not only induce the
      production of otherwise not observed metabolites from so called sleeping genes
      but alter the products from well-studied biosynthetic pathways. 

PMID- 25760403
TI  - Navigating Organo-Lead Halide Perovskite Phase Space via Nucleation Kinetics
      toward a Deeper Understanding of Perovskite Phase Transformations and Structure
      Property Relationships.
AB  - Organo-lead halide perovskite photovoltaics have developed faster than our
      understanding of the material itself. Using the vast body of work on perovskite
      processing created in just the past few years, it is possible to create a better
      picture of this material's complex phase-transformation behavior. This concept
      paper summarizes and correlates the current understanding of structural
      intermediates, kinetic controls, and structure-property relationships of organo
      lead iodide perovskites. To this end, a new way of graphically relating
      information is developed, allowing the simultaneous mapping of schematic kinetic
      relationships between all currently prevailing perovskite deposition and growth
      techniques. 

PMID- 25760404
TI  - BaAMPs: the database of biofilm-active antimicrobial peptides.
AB  - Antimicrobial peptides (AMPs) are increasingly being considered as novel agents
      against biofilms. The development of AMP-based anti-biofilm strategies strongly
      relies on the design of sequences optimized to target specific features of
      sessile bacterial/fungal communities. Although several AMP databases have been
      created and successfully exploited for AMP design, all of these use data
      collected on peptides tested against planktonic microorganisms. Here, an open
      access, manually curated database of AMPs specifically assayed against microbial
      biofilms (BaAMPs) is presented for the first time. In collecting relevant data
      from the literature an effort was made to define a minimal standard set of
      essential information including, for each AMP, the microbial species and biofilm
      conditions against which it was tested, and the specific assay and peptide
      concentration used. The availability of these data in an organized framework will
      benefit anti-biofilm research and support the design of novel molecules active
      against biofilm. BaAMPs is accessible at http://www.baamps.it. 

PMID- 25760405
TI  - Environmental impacts of genetically modified (GM) crop use 1996-2013: Impacts on
      pesticide use and carbon emissions.
AB  - This paper updates previous assessments of how crop biotechnology has changed the
      environmental impact of global agriculture. It focuses on the environmental
      impacts associated with changes in pesticide use and greenhouse gas emissions
      arising from the use of GM crops since their first widespread commercial use in
      the mid 1990s. The adoption of GM insect resistant and herbicide tolerant
      technology has reduced pesticide spraying by 553 million kg (-8.6%) and, as a
      result, decreased the environmental impact associated with herbicide and
      insecticide use on these crops (as measured by the indicator the Environmental
      Impact Quotient (EIQ)) by 19.1%. The technology has also facilitated important
      cuts in fuel use and tillage changes, resulting in a significant reduction in the
      release of greenhouse gas emissions from the GM cropping area. In 2013, this was
      equivalent to removing 12.4 million cars from the roads.

PMID- 25760407
TI  - Preparation and characterization of a composite hydrogel with graphene oxide as
      an acid catalyst.
AB  - In this study, a facile method for synthesizing a novel graphene oxide/pyrrole
      formaldehyde (GOP-1) composite hydrogel was developed via in situ polymerization
      of pyrrole and formaldehyde in the presence of graphene oxide sheets without any
      additional catalyst. During the polymerization, graphene oxide can act as a two
      dimensional template to regulate the aggregation state of polymer and as an acid
      catalyst to accelerate the reaction rate of pyrrole and formaldehyde. The
      morphology and microstructure were investigated by scanning electron microscopy,
      transmission electron microscopy, and X-ray diffraction, respectively. The
      chemical properties were analyzed via X-ray photoelectron spectroscopy, infrared
      spectroscopy, and Raman spectroscopy. The freeze-dried GOP-1 composite hydrogel
      exhibited a large specific surface area, high nitrogen content, and three
      dimensional network structure. Based on the above features, the freeze-dried GOP
      1 composite hydrogel used as a gas adsorbent showed a high carbon dioxide uptake
      capacity at 1.0 bar and 273 K (11.1 wt%), in sharp contrast to that of graphene
      oxide (7.4 wt%). Furthermore, the as-prepared composite hydrogel may possess
      attractive potential in the fields of electrode material, tissue engineering, and
      water treatment. 

PMID- 25760406
TI  - Development of an observation platform for bacterial activity using polypyrrole
      films doped with bacteria.
AB  - In our study, various bacteria, including Gram-negative (Pseudomonas aeruginosa,
      Escherichia coli, Acinetobacter calcoaceticus, Serratia marcescens, Shewanella
      oneidensis) and Gram-positive (Bacillus subtilis) bacteria, were
      straightforwardly immobilized into the conducting polymers (CPs) by
      electrochemical deposition. The doping state of bacteria in the polymer films
      (polypyrrole and poly(3,4-ethylenedioxythiophene)) varied according to the
      polymerization conditions. The viability of bacteria in the polymers and of those
      adsorbed on various substrates was evaluated. The activity of bacteria doped on
      the polymer film was evaluated by cyclic voltammetry in a thin-layer cell. 

PMID- 25760408
TI  - Leaf proteome comparison of two GM common bean varieties and their non-GM
      counterparts by principal component analysis.
AB  - BACKGROUND: A genetically modified (GM) common bean event, namely Embrapa 5.1,
      was approved for commercialization in Brazil. The present work aimed to use
      principal component analysis (PCA) to compare the proteomic profile of this GM
      common bean and its non-GM counterpart. RESULTS: Seedlings from four Brazilian
      common bean varieties were grown under controlled environmental conditions. Leaf
      proteomic profiles were analyzed by two-dimensional gel electrophoresis (2DE).
      First, a comparison among 12 gels from four common bean varieties was performed
      by PCA using volume percentage of 198 matched spots, presented in all gels. The
      first two principal components (PC) accounted for 46.8% of total variation. Two
      groups were clearly separated by the first component: Perola and GM Perola from
      Pontal and GM Pontal. Secondly, another comparison among six gels from the same
      variety GM and its non-GM counterpart was performed by PCA; in this case it was
      possible to distinguish GM and non-GM. CONCLUSION: Separation between leaf
      proteomic profile of GM common bean variety and its counterpart was observed only
      when they were compared in pairs. These results showed higher similarity between
      GM variety and its counterpart than between two common bean varieties. PCA is a
      useful tool to compare proteomes of GM and non-GM plant varieties.

PMID- 25760410
TI  - A general, scalable, organocatalytic nitro-Michael addition to enones:
      enantioselective access to all-carbon quaternary stereocenters.
AB  - A tert-leucine-derived chiral diamine catalyzes the asymmetric Michael addition
      of nitromethane to five-, six-, and seven-membered beta-substituted cyclic enones
      with excellent enantioselectivity, offering scalable, asymmetric access to all
      carbon quaternary stereocenters. The reaction scope can be expanded to include
      linear acyclic enones, and excellent levels of enantioselectivity are also
      observed. Furthermore, this organocatalytic, asymmetric nitro-Michael reaction is
      amenable to multigram scale-up and applications in the construction of an
      eudesmane sesquiterpenoid skeleton. 

PMID- 25760409
TI  - Lead optimization toward proof-of-concept tools for Huntington's disease within a
      4-(1H-pyrazol-4-yl)pyrimidine class of pan-JNK inhibitors.
AB  - Through medicinal chemistry lead optimization studies focused on calculated
      properties and guided by X-ray crystallography and computational modeling, potent
      pan-JNK inhibitors were identified that showed submicromolar activity in a
      cellular assay. Using in vitro ADME profiling data, 9t was identified as
      possessing favorable permeability and a low potential for efflux, but it was
      rapidly cleared in liver microsomal incubations. In a mouse pharmacokinetics
      study, compound 9t was brain-penetrant after oral dosing, but exposure was
      limited by high plasma clearance. Brain exposure at a level expected to support
      modulation of a pharmacodynamic marker in mouse was achieved when the compound
      was coadministered with the pan-cytochrome P450 inhibitor 1-aminobenzotriazole. 

PMID- 25760411
TI  - Words of wisdom. Re: Cytoreductive radical prostatectomy in patients with
      prostate cancer and low volume skeletal metastases--results of a feasibility and
      case-control study.

PMID- 25760412
TI  - Words of wisdom. Re: Comparative effectiveness of robot-assisted versus open
      radical prostatectomy cancer control.

PMID- 25760413
TI  - Words of wisdom. Bladder cancers arise from distinct urothelial sub-populations.

PMID- 25760414
TI  - Words of wisdom. Ciprofloxacin resistance in the faecal carriage of patients
      undergoing transrectal ultrasound guided prostate biopsy.

PMID- 25760415
TI  - Words of wisdom. Re: Can selective arterial clamping with fluorescence imaging
      preserve kidney function during robotic partial nephrectomy?

PMID- 25760416
TI  - Words of wisdom. Re: Overall survival advantage with partial nephrectomy: a bias
      of observational data?

PMID- 25760418
TI  - Corrigendum to "Current perspectives in the use of molecular imaging to target
      surgical treatments for genitourinary cancers" [Eur Urol 2014;65:947-64].

PMID- 25760420
TI  - MyD88 dependence of beryllium-induced dendritic cell trafficking and CD4+ T-cell
      priming.
AB  - Beryllium exposure results in beryllium hypersensitivity in a subset of exposed
      individuals, leading to granulomatous inflammation and fibrosis in the lung. In
      addition to its antigenic properties, beryllium has potent adjuvant activity that
      contributes to sensitization via unknown pathways. Here we show that beryllium
      induces cellular death and release of interleukin (IL)-1alpha and DNA into the
      lung. Release of IL-1alpha was inflammasome independent and required for
      beryllium-induced neutrophil recruitment into the lung. Beryllium enhanced
      classical dendritic cell (cDC) migration from the lung to draining lymph nodes
      (LNs) in an IL-1R-independent manner, and the accumulation of activated cDCs in
      the LN was associated with increased priming of CD4(+) T cells. DC migration was
      reduced in Toll-like receptor 9 knockout (TLR9KO) mice; however, cDCs in the LNs
      of TLR9-deficient mice were highly activated, suggesting a role for more than one
      innate receptor in the effects on DCs. The adjuvant effects of beryllium on
      CD4(+) T-cell priming were similar in wild-type, IL-1R-, caspase-1-, TLR2-, TLR4
      , TLR7-, and TLR9-deficient mice. In contrast, DC migration, activation, and the
      adjuvant effects of beryllium were significantly reduced in myeloid
      differentiation primary response gene 88 knockout (MyD88KO) mice. Collectively,
      these data suggest that beryllium exposure results in the release of damage
      associated molecular patterns that engage MyD88-dependent receptors to enhance
      pulmonary DC function. 

PMID- 25760422
TI  - Discrete stimuli-responsive multirotaxanes with supramolecular cores constructed
      through a modular approach.
AB  - The synthesis of discrete multirotaxanes with well-defined structures remains a
      great challenge. Herein, we present the successful construction of diverse
      discrete multirotaxanes with well-defined supramolecular metallacycles as cores
      by a modular approach. Moreover, these novel multirotaxanes featured a stimuli
      responsive property that enabled the introduction and removal of the bromide
      anion by taking advantage of dynamic nature of the supramolecular metallacycle
      scaffold. Through the combination of rotaxane-containing prefunctionalized
      building blocks with the corresponding different organoplatinum(II) acceptor
      building blocks (60, 120, or 180 degrees ), diverse discrete multirotaxanes with
      well-defined metallacycles (rhomboid or hexagon) as cores as well as certain
      numbers of rotaxane units were successfully obtained quantitatively by means of
      coordination-driven self-assembly. Furthermore, owing to the existence of a
      dynamic metallacycle as the supramolecular cores, the resultant multirotaxanes
      showed anion-induced disassembly and reassembly properties, which allowed for the
      reversible transformation between multirotaxanes and the corresponding individual
      rotaxane-containing building blocks. Therefore, this research not only enriches
      the family of discrete multirotaxanes, but also provides a novel strategy for the
      construction of "smart" stimuli-responsive multirotaxane systems. 

PMID- 25760421
TI  - Neutralizing TNFalpha restores glucocorticoid sensitivity in a mouse model of
      neutrophilic airway inflammation.
AB  - Asthma is a heterogeneous disorder, evidenced by distinct types of inflammation
      resulting in different responsiveness to therapy with glucocorticoids (GCs).
      Tumor necrosis factor alpha (TNFalpha) is involved in asthma pathogenesis, but
      anti-TNFalpha therapies have not proven broadly effective. The effects of anti
      TNFalpha treatment on steroid resistance have never been assessed. We
      investigated the role of TNFalpha blockade using etanercept in the responsiveness
      to GCs in two ovalbumin-based mouse models of airway hyperinflammation. The first
      model is GC sensitive and T helper type 2 (Th2)/eosinophil driven, whereas the
      second reflects GC-insensitive, Th1/neutrophil-predominant asthma subphenotypes.
      We found that TNFalpha blockade restores the therapeutic effects of GCs in the GC
      insensitive model. An adoptive transfer indicated that the TNFalpha-induced GC
      insensitivity occurs in the non-myeloid compartment. Early during airway
      hyperinflammation, mice are GC insensitive specifically at the level of thymic
      stromal lymphopoietin (Tslp) transcriptional repression, and this insensitivity
      is reverted when TNFalpha is neutralized. Interestingly, TSLP knockout mice
      displayed increased inflammation in the GC-insensitive model, suggesting a
      limited therapeutic application of TSLP-neutralizing antibodies in subsets of
      patients suffering from Th2-mediated asthma. In conclusion, we demonstrate that
      TNFalpha reduces the responsiveness to GCs in a mouse model of neutrophilic
      airway inflammation. Thus antagonizing TNFalpha may offer a new strategy for
      therapeutic intervention in GC-resistant asthma. 

PMID- 25760423
TI  - A Multicenter, Single-Blind, Phase IIa Clinical Trial to Evaluate the Efficacy
      and Safety of a Cell-Mediated Gene Therapy in Degenerative Knee Arthritis
      Patients.
AB  - Osteoarthritis leads to articular cartilage wear, and newer therapies are aimed
      at slowing this degeneration. Growth factors and cytokines influence cartilage
      formation, and researchers are studying their use on cartilage regeneration in
      osteoarthritis. One method uses genetically engineered cells to deliver growth
      factors to damaged cartilage. This technique utilizes transforming growth factor
      beta proteins in modified chondrocytes to stimulate cartilage growth via an intra
      articular injection. We evaluated the efficacy and outcomes of this injection on
      patients who had International Cartilage Repair Society grade 4 knee
      osteoarthritis. We evaluated 27 patients (6 men, 21 women) who had late-stage
      knee osteoarthritis. Patients were randomized to receive genetically engineered
      chondrocytes doses of 6*10(6) cells (group 1) or 1.8*10(7) cells (group 2) at a
      1:1 ratio. Primary endpoints were subjective and functional evaluations, assessed
      by the International Knee Documentation Committee (IKDC) score. Secondary
      endpoints were pain severity and physical function, using the Western Ontario and
      McMaster osteoarthritis (WOMAC) index and the 100 mm visual analog scale (VAS).
      Patients were followed at 2, 4, 12, and 24 weeks postinjection. Both groups had
      significant improvements in outcomes. Scores improved at 12 and 24 weeks from
      baseline in IKDC (+10 and +14 points in group 1; +11 and +13 points in group 2),
      WOMAC (-12 and -13 points in group 1; -10 and -12 points in group 2), and VAS (
      19 and -24 points in group 1; -20 and -20 in group 2) scores. Additionally, there
      were no serious adverse events, and no significant difference in adverse event
      incidence between the groups. Both groups expressed a mean improvement in pain,
      function, and physical ability following treatment injection. This modality
      appears to be a promising treatment for cartilage degeneration. However, further
      larger, multicenter, randomized studies are needed to truly evaluate the efficacy
      of this novel approach. 

PMID- 25760424
TI  - Electrophysiological analysis shows dizziness as the first symptom in human T
      cell lymphotropic virus type-associated myelopathy/tropical spastic paraparesis.
AB  - Dizziness is a symptom in human T cell lymphotropic virus type-associated
      myelopathy/tropical spastic paraparesis (HAM/TSP) and may occur due to
      vestibulospinal tract dysfunction. This tract can be assessed by an
      electrophysiological test called vestibular-evoked myogenic potential (VEMP). The
      aim was to correlate the result of VEMP generated by acoustic stimuli and
      dizziness in individuals with human T cell lymphotropic virus type 1 (HTLV-1)
      asymptomatic infection and HAM/TSP. VEMP was recorded from the
      sternocleidomastoid muscle of 60 HTLV-1-negative adults (60+/-8 years) and 60
      individuals infected with HTLV-1, 30 being asymptomatic (59+/-8 years) and 30
      with HAM/TSP (59+/-8 years). In all groups, 90% of the participants were women.
      VEMP was generated by acoustic stimuli (short tone bursts), with an intensity of
      118 dBHL and band-pass filter from 10 Hz to 1,500 Hz, and presented 200 stimuli
      at a frequency of 1,000 Hz with a record time of 60 ms. Of 60 HTLV-1-negative
      individuals, 14 (23%) reported dizziness; VEMP was normal in all. In the HTLV-1
      asymptomatic group, 11(37%) complained of dizziness (p=0.31); VEMP was altered in
      four (40%) subjects with dizziness and in one (5%) without dizziness (p=0.00). In
      the group with HAM/TSP, dizziness was reported by 17 (57%) subjects (p=0.002);
      VEMP was altered in 11 (64%) with dizziness and in 5 (38%) without dizziness
      (p=0.15). Dizziness without an apparent etiology in HTLV-1-asymptomatic carriers
      deserves attention in terms of a possible subclinical spinal cord involvement
      that can be clarified through spinal electrophysiological tests. Damage of the
      vestibulospinal tract seems to occur in the early stages of HAM/TSP. 

PMID- 25760425
TI  - Ex vivo optical measurements of glucose diffusion kinetics in native and diabetic
      mouse skin.
AB  - The aim of this study was to estimate the glucose diffusion coefficients ex vivo
      in skin of mice with diabetes induced in vivo by alloxan in comparison to non
      diabetic mice. The temporal dependences of collimated transmittance of tissue
      samples immersed in glucose solutions were measured in the VIS-NIR spectral range
      to quantify the glucose diffusion/permeability coefficients and optical clearing
      efficiency of mouse skin. The average thickness of intact healthy and diabetic
      skin was 0.023 +/- 0.006 cm and 0.019 +/- 0.005 cm, respectively. Considerable
      differences in optical and kinetic properties of diabetic and non-diabetic skin
      were found: clearing efficiency was 1.5-fold better and glucose diffusivity was 2
      fold slower for diabetic skin. Experimental Setup for measuring collimated
      transmittance spectra of mouse skin samples. 

PMID- 25760426
TI  - Enhancement of electrical conductivity of silver nanowires-networked films via
      the addition of Cs-added TiO2.
AB  - This study proposes a novel method of improving the electrical conductivity of
      silver nanowires (NWs)-networked films for the application of transparent
      conductive electrodes. We applied Cs-added TiO2 (TiO2:Cs) nanoparticles onto Ag
      NWs, which caused the NWs to be neatly welded together through local melting at
      the junctions, according to our transmission and scanning electron microscopy
      analyses. Systematic comparison of the sheet resistance of the samples reveals
      that these welded NWs yielded a significant improvement in conductivity. OLED
      devices, fabricated by using the NW film planarized via embedding the wires into
      PMMA, demonstrated device performance was comparable with the reference sample
      with indium tin oxide electrode. 

PMID- 25760427
TI  - Medical versus surgical management for emphysematous pancreatic necrosis: is gas
      within pancreatic necrosis an absolute indication for surgery?
AB  - OBJECTIVES: The aim of this study was to evaluate whether pancreatic necrosis
      with presence of gas is an absolute indication for surgery or if there is a
      possibility for the medical management of this pathology. METHODS: This study is
      a retrospective study including 56 patients with diagnosis of pancreatic necrosis
      and gas on computed tomography from April 2003 to March 2011. We recorded all the
      factors related to each group of treatment, including APACHE II score, C-reactive
      protein level, Tomographic Severity Index, organ and multiorgan failure, and
      infected necrosis after fine-needle puncture, to evaluate the differences between
      surgical and medical treatment. RESULTS: Thirty-six (64%) of these patients were
      submitted to surgery, whereas 20 (36%) were managed conservatively. Twenty-eight
      patients (78%) who underwent surgery had infected necrosis. Thirty-five percent
      of the patients (7 patients) in the medical group had organ failure versus 83% of
      the patients in the surgical group. CONCLUSIONS: Pancreatic necrosis with gas on
      computed tomography is a relative indication for surgery. Medical management is a
      feasible and safe possibility for this pathology in selected cases. The presence
      of organ failure and infected necrosis often precludes a surgical treatment.

PMID- 25760428
TI  - Protective effects of polyenoylphosphatidylcholine in rats with severe acute
      pancreatitis.
AB  - OBJECTIVE: The aim of this study was to investigate the protective effect of
      polyenoylphosphatidylcholine (PPC) in rats with severe acute pancreatitis (SAP)
      and its mechanism. METHODS: Seventy-two clean, conventional Sprague-Dawley rats
      were randomly divided into 4 groups (SAP; sham operation [SO], SAP + PPC, and SO
      + PPC; n = 18 per group). The SAP model was induced by injecting 4% sodium
      taurocholate (1 mL/kg) into the biliopancreatic duct. Animals in the SO groups
      underwent laparotomy and biliopancreatic duct puncture without fluid injection.
      Polyenoylphosphatidylcholine (50 mg/kg) was injected through the penis dorsal
      vein. Pancreatic acinar cell membrane fluidity and pancreatic tissue calcium pump
      activity were measured through fluorescence polarization and quantization of
      phosphonium ions, whereas pancreatic tissue superoxide dismutase and
      malondialdehyde were detected through xanthine oxidase method and thiobarbituric
      acid colorimetric analysis method, respectively. RESULTS: The SAP + PPC group had
      significantly improved pathologic pancreas; increased in pancreatic acinar cell
      membrane fluidity, pancreatic tissue Ca-Mg-ATPase activity, and superoxide
      dismutase; as well as decreased in malondialdehyde, ascites volume, and serum
      amylase compared with the SAP group. CONCLUSIONS: Polyenoylphosphatidylcholine
      could reduce the damage to the pancreas through increasing pancreatic acinar cell
      membrane fluidity and pancreatic tissue calcium pump activity.
      Polyenoylphosphatidylcholine also scavenges oxygen free radicals and reduces
      lipid peroxide levels.

PMID- 25760429
TI  - SMAD4 expression predicts local spread and treatment failure in resected
      pancreatic cancer.
AB  - OBJECTIVE: The purpose of this study was to evaluate the prognostic relevance of
      SMAD4 expression in pancreatic cancer. METHODS: We analyzed the correlations
      between SMAD4 expression and clinicopathological parameters and outcome in 174
      patients with pancreatic cancer. Specimens were also classified into subtypes
      reflecting epithelial-to-mesenchymal transition, based on E-cadherin and
      vimentin. RESULTS: We found that 59.8% (104/174) of patients were SMAD4 and 40.2%
      (70/174) were SMAD4. Disease-specific survival in patients with SMAD4 was
      significantly better than that in SMAD4. SMAD4 status was significantly
      correlated with portal vein invasion, lymph vessel invasion, and perineural
      invasion and was an independent prognostic factor. SMAD4 was significantly
      associated with mesenchymal phenotype. The loss of SMAD4 expression was found in
      49.4% of patients with no vascular invasion, 61.9% with portal vein invasion,
      76.5% with common hepatic artery invasion, and 80.8% with superior mesenteric
      artery invasion. In addition, the specimens from 59.0% of patients with local
      recurrence, 66.7% of those with both local and distant recurrence, and 73.7% of
      those with distant recurrence were SMAD4. CONCLUSIONS: The loss of SMAD4
      expression is an independent prognostic factor and seems to be associated with
      tumor progression, pattern of failure, and epithelial-to-mesenchymal transition
      status. Preoperative stratification based on SMAD4 could lead to appropriate
      treatment strategy.

PMID- 25760430
TI  - High temperature neutron diffraction studies of PrInO3 and the measures of
      perovskite structure distortion.
AB  - The crystal structure of PrInO(3) was investigated in the temperature range 303
      1123 K by high-resolution neutron-powder diffraction. The PrInO(3) adopts a
      highly distorted variant of the perovskite structure with the orthorhombic Pnma
      space group in the whole temperature range investigated. The bond length and bond
      angle analysis revealed a very slow tendency to decrease structural distortion
      with increasing temperature. Comparison of different parameters quantifying
      perovskite structure distortion calculated for PrInO(3) and the similar PrAlO(3)
      and PrGaO(3) shows the advantage of using the tolerance factor t12 calculated for
      the 12-fold coordinated Pr by geometrical averaging of the individual interatomic
      distances. An additional advantage of the tolerance factor method results from
      the possibility of extending it to predict the average structural distortion and
      the geometrical stability of the perovskites at various temperatures once the
      accurate dependence of t(x,T,d) on the composition, temperature and oxygen
      content is found. By comparing PrInO(3) with several AMO(3) perovskites
      containing ions in the fixed oxidation state on the A and M crystal sites it was
      found that structural distortion and the tolerance factor t12 for PrInO(3) are
      consistent with the empirical thermal expansion coefficient based on the bond
      strength calculation [R. M. Hazen, and C. T. Prewitt, Am. Mineral., 1977, 62(3
      4), 309]. In contrast to perovskites AMO(3-d) containing mixed-valent M ions,
      which allow for a wide range of changes of the tolerance factor t(12)(T,d) as a
      function of oxygen content, perovskites AMO(3) with M ions in the fixed oxidation
      state show much less flexibility. This flexibility is further reduced for the
      A(3+)M(3+)O(3) perovskites like PrInO(3) for which even a large change of the
      synthesis temperature has a minor effect on controlling the resulting t(12)(T)
      and the structural phase in comparison with A(2+)M(4+)O3 perovskites. The only
      parameter left for A(3+)M(3+)O(3) materials allowing formation of various
      perovskites and hexagonal phases is the total pressure, which may significantly
      change t(12)(T,P).

PMID- 25760431
TI  - The effects of sedentary behavior on metabolic syndrome independent of physical
      activity and cardiorespiratory fitness.
AB  - BACKGROUND: To date, no longitudinal studies have examined the influence of
      sedentary behavior on metabolic syndrome development while accounting for
      cardiorespiratory fitness. PURPOSE AND METHODS: This prospective study examined
      the relationship between sedentary behavior and incident metabolic syndrome while
      considering the effects of physical activity and cardiorespiratory fitness on the
      association among 930 men enrolled in the Aerobics Center Longitudinal Study.
      RESULTS: A total of 124 men developed metabolic syndrome during 8974 person-years
      of exposure. After adjusting for covariates, men with middle and high sedentary
      behavior had 65% and 76% higher risks of developing metabolic syndrome,
      respectively, than men with low sedentary behavior (linear trend P = .011). This
      association remained significant after additional adjustment for activity status
      and cardiorespiratory fitness. Cardiorespiratory fitness and physical activity
      were also inversely associated with metabolic syndrome, even after adjustment for
      sedentary behavior. CONCLUSIONS: The findings highlight the importance of
      reducing sedentary behavior, increasing physical activity, and improving
      cardiorespiratory fitness for preventing metabolic syndrome.

PMID- 25760433
TI  - A review of methods for identifying stochastic resonance in simulations of single
      neuron models.
AB  - Stochastic resonance (SR) is said to be observed when the presence of noise in a
      nonlinear system enables an output signal from the system to better represent
      some feature of an input signal than it does in the absence of noise. The effect
      has been observed in models of individual neurons, and in experiments performed
      on real neural systems. Despite the ubiquity of biophysical sources of stochastic
      noise in the nervous system, however, it has not yet been established whether
      neuronal computation mechanisms involved in performance of specific functions
      such as perception or learning might exploit such noise as an integral component,
      such that removal of the noise would diminish performance of these functions. In
      this paper we revisit the methods used to demonstrate stochastic resonance in
      models of single neurons. This includes a previously unreported observation in a
      multicompartmental model of a CA1-pyramidal cell. We also discuss, as a contrast
      to these classical studies, a form of 'stochastic facilitation', known as inverse
      stochastic resonance. We draw on the reviewed examples to argue why new
      approaches to studying 'stochastic facilitation' in neural systems need to be
      developed. 

PMID- 25760435
TI  - Nonviral Reprogramming of Human Wharton's Jelly Cells Reveals Differences Between
      ATOH1 Homologues.
AB  - The transcription factor atonal homolog 1 (ATOH1) has multiple homologues that
      are functionally conserved across species and is responsible for the generation
      of sensory hair cells. To evaluate potential functional differences between
      homologues, human and mouse ATOH1 (HATH1 and MATH-1, respectively) were
      nonvirally delivered to human Wharton's jelly cells (hWJCs) for the first time.
      Delivery of HATH1 to hWJCs demonstrated superior expression of inner ear hair
      cell markers and characteristics than delivery of MATH-1. Inhibition of HES1 and
      HES5 signaling further increased the atonal effect. Transfection of hWJCs with
      HATH1 DNA, HES1 siRNA, and HES5 siRNA displayed positive identification of key
      hair cell and support cell markers found in the cochlea, as well as a variety of
      cell shapes, sizes, and features not native to hair cells, suggesting the need
      for further examination of other cell types induced by HATH1 expression. In the
      first side-by-side evaluation of HATH1 and MATH-1 in human cells, substantial
      differences were observed, suggesting that the two atonal homologues may not be
      interchangeable in human cells, and artificial expression of HATH1 in hWJCs
      requires further study. In the future, this line of research may lead to
      engineered systems that would allow for evaluation of drug ototoxicity or
      potentially even direct therapeutic use. 

PMID- 25760436
TI  - A comprehensive library of familial human amyotrophic lateral sclerosis induced
      pluripotent stem cells.
AB  - Amyotrophic lateral sclerosis is a progressive disease characterized by the loss
      of upper and lower motor neurons, leading to paralysis of voluntary muscles.
      About 10% of all ALS cases are familial (fALS), among which 15-20% are linked to
      Cu/Zn superoxide dismutase (SOD1) mutations, usually inherited in an autosomal
      dominant manner. To date only one FDA approved drug is available which increases
      survival moderately. Our understanding of ALS disease mechanisms is largely
      derived from rodent model studies, however due to the differences between rodents
      and humans, it is necessary to have humanized models for studies of disease
      pathogenesis as well as drug development. Therefore, we generated a comprehensive
      library of a total 22 of fALS patient-specific induced pluripotent stem cell
      (iPSC) lines. These cells were thoroughly characterized before being deposited
      into the library. The library of cells includes a variety of C9orf72 mutations,
      sod1 mutations, FUS, ANG and FIG4 mutations. Certain mutations are represented
      with more than one line, which allows for studies of variable genetic
      backgrounds. In addition, these iPSCs can be successfully differentiated to
      astroglia, a cell type known to play a critical role in ALS disease progression.
      This library represents a comprehensive resource that can be used for ALS disease
      modeling and the development of novel therapeutics. 

PMID- 25760437
TI  - RNA silencing of integrin-linked kinase increases the sensitivity of the A549
      lung cancer cell line to cisplatin and promotes its apoptosis.
AB  - The expression of integrin-linked kinase (ILK) has been reported to be involved
      in the regulation of integrin-mediated processes, including cancer cell
      proliferation, migration and invasion. Previous studies have demonstrated that
      inhibition of ILK may be an underlying approach for treating cancer. However,
      whether the knock down of ILK affects growth and apoptosis of lung cancer cells
      remains to be elucidated. Importantly, whether downregulation of ILK increases
      the sensitivity of lung cancer cells to cisplatin and amplifies cell apoptosis
      also remains to be elucidated. In the present study, ILK downregulation was
      mediated by lentivirus-mediated RNA interference. The expression levels of
      associated genes were determined by reverse-transcription quantitative polymerase
      chain reaction and western blotting. Cell proliferation was evaluated using a
      modified 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and
      clone formation assay. The cell cycle and apoptosis were analyzed using flow
      cytometry. The current data revealed that lentivirus-mediated ILK gene silencing
      alone inhibited A549 cell proliferation and promotes cell cycle arrest, however,
      had no detectable effect on cell apoptosis. However, combined treatment with
      lentivirus-mediated ILK interference and cisplatin chemotherapy induced
      significantly more cell apoptosis than mono-chemotherapy or knockdown. The
      increased cell apoptosis and proliferation inhibition were attributed to abnormal
      downstream protein expression of ILK, including phospho-glycogen synthase kinase
      3beta, p-AKT, activator protein-1, beta-catenin, cyclin D1 and matrix
      metalloproteinase-9. ILK inhibition may suppress the proliferation of A549 and
      increase A549 sensitivity to cisplatin. The combined treatment of ILK gene
      knockdown and chemotherapy has the potential to improve anticancer efficacy.

PMID- 25760439
TI  - The bitter side of sweet: the role of Galectin-9 in immunopathogenesis of viral
      infections.
AB  - In recent years, a critical role for beta-galactoside-binding protein, Galectin-9
      (Gal-9) has emerged in infectious disease, autoimmunity, and cancer. It is a
      ligand for T cell immunoglobulin mucin domain 3 (Tim-3), a type-I glycoprotein
      that is persistently expressed on dysfunctional T cells during chronic viral
      infections. Gal-9 exerts its pivotal immunomodulatory effects by inducing
      apoptosis or suppressing effector functions via engagement with its receptor, Tim
      3. Recent studies report elevation of circulating Gal-9 in humans infected with
      different viral infections. Interaction of soluble Gal-9 with Tim-3 expressed on
      the surface of activated CD4+ T cells renders them less susceptible to HIV-1
      infection, while enhanced HIV infection occurs when Gal-9 interacts with a
      different receptor than Tim-3. This indicates the versatile role of Gal-9 in
      viral pathogenesis. For instance, higher expression of Tim-3 during chronic viral
      infection and elevation of plasma Gal-9 may have evolved to limit persistent
      immune activation and pathogenic T cells activity. In contrast, Gal-9 can
      suppress the effectiveness of immunity against viral infections. In agreement,
      Gal-9 knockout mice mount a more robust and vigorous virus-specific immune
      response in acute and chronic viral infections resulting in rapid viral
      clearance. In line with this observation, blocking Gal-9 signals to Tim-3
      expressing T cells result in improved immune responses. Here we review the
      biological and immunological properties of Gal-9 in viral infections (HIV, HCV,
      HBV, HSV, CMV, influenza, and dengue virus). Manipulating Gal-9 signals may have
      immunotherapeutic potential and could represent an alternative approach for
      improving immune responses to viral infections/vaccines.

PMID- 25760438
TI  - First genome-wide association study in an Australian aboriginal population
      provides insights into genetic risk factors for body mass index and type 2
      diabetes.
AB  - A body mass index (BMI) >22kg/m2 is a risk factor for type 2 diabetes (T2D) in
      Aboriginal Australians. To identify loci associated with BMI and T2D we undertook
      a genome-wide association study using 1,075,436 quality-controlled single
      nucleotide polymorphisms (SNPs) genotyped (Illumina 2.5M Duo Beadchip) in 402
      individuals in extended pedigrees from a Western Australian Aboriginal community.
      Imputation using the thousand genomes (1000G) reference panel extended the
      analysis to 6,724,284 post quality-control autosomal SNPs. No associations
      achieved genome-wide significance, commonly accepted as P<5x10-8. Nevertheless,
      genes/pathways in common with other ethnicities were identified despite the
      arrival of Aboriginal people in Australia >45,000 years ago. The top hit
      (rs10868204 Pgenotyped = 1.50x10-6; rs11140653 Pimputed_1000G = 2.90x10-7) for
      BMI lies 5' of NTRK2, the type 2 neurotrophic tyrosine kinase receptor for brain
      derived neurotrophic factor (BDNF) that regulates energy balance downstream of
      melanocortin-4 receptor (MC4R). PIK3C2G (rs12816270 Pgenotyped = 8.06x10-6;
      rs10841048 Pimputed_1000G = 6.28x10-7) was associated with BMI, but not with T2D
      as reported elsewhere. BMI also associated with CNTNAP2 (rs6960319 Pgenotyped =
      4.65x10-5; rs13225016 Pimputed_1000G = 6.57x10-5), previously identified as the
      strongest gene-by-environment interaction for BMI in African-Americans. The top
      hit (rs11240074 Pgenotyped = 5.59x10-6, Pimputed_1000G = 5.73x10-6) for T2D lies
      5' of BCL9 that, along with TCF7L2, promotes beta-catenin's transcriptional
      activity in the WNT signaling pathway. Additional hits occurred in genes
      affecting pancreatic (KCNJ6, KCNA1) and/or GABA (GABRR1, KCNA1) functions.
      Notable associations observed for genes previously identified at genome-wide
      significance in other populations included MC4R (Pgenotyped = 4.49x10-4) for BMI
      and IGF2BP2 Pimputed_1000G = 2.55x10-6) for T2D. Our results may provide novel
      functional leads in understanding disease pathogenesis in this Australian
      Aboriginal population. 

PMID- 25760440
TI  - Passive smoking in the etiology of non-syndromic orofacial clefts: a systematic
      review and meta-analysis.
AB  - BACKGROUND: Studies have found a consistent positive association between maternal
      smoking and non-syndromic orofacial clefts (NSOFC). However, no comprehensive
      assessment of the association between NSOFC and passive smoking has been
      undertaken. This systematic review and meta-analysis explores the relationship
      between maternal passive smoking and NSOFC, and compares the associations between
      passive and active smoking. METHODS AND FINDINGS: Search strategy, inclusion /
      exclusion criteria, and data extraction from studies reporting maternal passive
      smoking and NSOFC was implemented without language restrictions. Risks of bias in
      the identified studies were assessed and this information was used in sensitivity
      analyses to explain heterogeneity. Meta-analysis and meta-regression of the
      extracted data were performed. Egger's test was used to test for small study
      effects. Fourteen eligible articles were identified. Maternal passive smoking
      exposure was associated with a twofold increase in risk of NSOFC (odds ratio:
      2.11, 95% confidence interval: 1.54-2.89); this was apparent for both cleft lip
      with and without palate (OR: 2.05, 95% CI: 1.27-3.3) and cleft palate (OR: 2.11,
      95% CI: 1.23-3.62). There was substantial heterogeneity between studies. In the
      studies that provided data enabling crude and adjusted odd ratios to be compared,
      adjustment for potential confounders attenuated the magnitude of association to
      about a 1.5-fold increase in risk. CONCLUSION: Overall, maternal passive smoking
      exposure results in a 1.5 fold increase in risk of NSOFC, similar to the
      magnitude of risk reported for active smoking, but there is marked heterogeneity
      between studies. This heterogeneity is not explained by differences in the
      distribution of cleft types, adjustment for covariates, broad geographic region,
      or study bias/quality. This thorough meta-analysis provides further evidence to
      minimize exposure to environmental tobacco smoke in policy making fora and in
      health promotion initiatives.

PMID- 25760442
TI  - Oxidative Stress in Pathophysiological Conditions.

PMID- 25760443
TI  - Editorial: Financial Crisis, Drug Compliance and Cardiovascular Health-the GREECS
      Case?

PMID- 25760441
TI  - Establishment of HSV1 latency in immunodeficient mice facilitates efficient in
      vivo reactivation.
AB  - The establishment of latent infections in sensory neurons is a remarkably
      effective immune evasion strategy that accounts for the widespread dissemination
      of life long Herpes Simplex Virus type 1 (HSV1) infections in humans. Periodic
      reactivation of latent virus results in asymptomatic shedding and transmission of
      HSV1 or recurrent disease that is usually mild but can be severe. An in-depth
      understanding of the mechanisms regulating the maintenance of latency and
      reactivation are essential for developing new approaches to block reactivation.
      However, the lack of a reliable mouse model that supports efficient in vivo
      reactivation (IVR) resulting in production of infectious HSV1 and/or disease has
      hampered progress. Since HSV1 reactivation is enhanced in immunosuppressed hosts,
      we exploited the antiviral and immunomodulatory activities of IVIG (intravenous
      immunoglobulins) to promote survival of latently infected immunodeficient Rag
      mice. Latently infected Rag mice derived by high dose (HD), but not low dose
      (LD), HSV1 inoculation exhibited spontaneous reactivation. Following hyperthermia
      stress (HS), the majority of HD inoculated mice developed HSV1 encephalitis (HSE)
      rapidly and synchronously, whereas for LD inoculated mice reactivated HSV1
      persisted only transiently in trigeminal ganglia (Tg). T cells, but not B cells,
      were required to suppress spontaneous reactivation in HD inoculated latently
      infected mice. Transfer of HSV1 memory but not OVA specific or naive T cells
      prior to HS blocked IVR, revealing the utility of this powerful Rag latency model
      for studying immune mechanisms involved in control of reactivation. Crossing Rag
      mice to various knockout strains and infecting them with wild type or mutant HSV1
      strains is expected to provide novel insights into the role of specific cellular
      and viral genes in reactivation, thereby facilitating identification of new
      targets with the potential to block reactivation. 

PMID- 25760444
TI  - Immunization of knock-out alpha/beta interferon receptor mice against high lethal
      dose of Crimean-Congo hemorrhagic fever virus with a cell culture based vaccine.
AB  - Crimean-Congo hemorrhagic fever (CCHF) is an acute tick-borne zoonotic disease.
      The disease has been reported in many countries of Africa, Asia, the Middle East,
      and in Eurasia. During the past decade, new foci of CCHF have emerged in the
      Balkan Peninsula, southwest Russia, the Middle East, western China, India,
      Africa, and Turkey. CCHF virus produces severe hemorrhagic manifestations in
      humans with fatality rates up to 30%. Vaccine development efforts have been
      significantly hampered by a lack of animal models and therefore, no protective
      vaccine has been achieved. Lately, IFN alpha/beta receptor deficient (IFNAR-/-)
      mice have been established as a novel small animal model of CCHF virus infection.
      In the present study, we found that IFNAR-/- mice highly susceptible to CCHF
      virus Turkey-Kelkit06 strain. Immunization with the cell culture based vaccine
      elicited a significant level of protection against high dose challenge (1,000
      PPFU) with a homologous CCHF virus in IFNAR-/- mice. 

PMID- 25760447
TI  - Novel role of red wine-derived polyphenols in the prevention of Alzheimer's
      disease dementia and brain pathology: experimental approaches and clinical
      implications.

PMID- 25760445
TI  - Inhibition of the JAK2/STAT3 signaling pathway exerts a therapeutic effect on
      osteosarcoma.
AB  - Osteosarcoma (OS) is the most common type of malignant bone tumor. Despite
      aggressive multimodal treatments, including surgical resection, chemotherapy and
      adjunctive immunotherapies, patients with OS with high-grade malignancy have a
      poor five-year survival rate that has remained unchanged over the past two
      decades, highlighting the urgent requirement for novel therapeutic approaches.
      Signal transducers and activators of transcription 3 (STAT3) has been implicated
      as an oncogene and therapeutic target in a variety of neoplastic diseases. The
      aim of the present study was to determine whether inhibition of the janus kinase
      2 (JAK2)/STAT3 pathway by FLLL32, a specific JAK2/STAT3 inhibitor, is able to
      provide a potential therapy for OS. FLLL32 inhibited OS cell growth in vitro and
      delayed OS growth in an OS xenograft nude mouse model. STAT3 knockdown by short
      hairpin RNA delayed OS formation in vivo. Thus, the JAK2/STAT3 pathway is
      important in OS formation. Efficacy of the FLLL32 pharmacological inhibitor in
      delaying OS growth suggests that targeting JAK2/STAT3 may be a potential
      therapeutic strategy for patients with OS.

PMID- 25760446
TI  - The cystic fibrosis transmembrane conductance regulator as a biomarker in non
      small cell lung cancer.
AB  - An increased risk of non-small cell lung cancer (NSCLC) in cystic fibrosis (CF)
      patients and carriers of CF transmembrane conductance regulator (CFTR) mutations
      has been proposed. However, the role of CFTR in lung cancer remains
      controversial. In the present study, CFTR expression was assessed in 165 NSCLC
      tumors and 22 normal lung samples with validation in an independent series of 131
      samples. The effect of gain and loss of CFTR on the malignant behavior of NSCLC
      was examined. The effect of CFTR manipulation on tumor metastasis was examined in
      a mouse model. Expression of CFTR was downregulated in NSCLC (p=0.041). Low CFTR
      expression was correlated with advanced stage (p<0.001) and lymph node metastasis
      (p=0.009). Low CFTR expression was significantly associated with poor prognosis
      (overall survival: 45 vs. 36 months, p<0.0001; progression-free survival: 41 vs.
      30 months, p=0.007). Knockdown of CFTR in NSCLC cells enhanced malignant behavior
      (epithelial-mesenchymal transition, invasion and migration); in contrast,
      overexpression of CFTR suppressed cancer progression in vitro and in vivo. The
      tumor-suppressing effect of CFTR was associated with inhibition of multiple
      uPA/uPAR-mediated malignant traits in culture. These results show that CFTR plays
      a role in inhibition of NSCLC metastasis and suggest that CFTR may serve as a
      novel indicator for predicting adverse prognosis and metastasis in NSCLC
      patients.

PMID- 25760448
TI  - Congenital Chagas disease: an update.
AB  - Congenital infection with Trypanosoma cruzi is a global problem, occurring on
      average in 5% of children born from chronically infected mothers in endemic
      areas, with variations depending on the region. This presentation aims to focus
      on and update epidemiological data, research methods, involved factors, control
      strategy and possible prevention of congenital infection with T. cruzi.
      Considering that etiological treatment of the child is always effective if
      performed before one year of age, the diagnosis of infection in pregnant women
      and their newborns has to become the standard of care and integrated into the
      surveillance programs of syphilis and human immunodeficiency virus. In addition
      to the standard tests, polymerase chain reaction performed on blood of neonates
      of infected mothers one month after birth might improve the diagnosis of
      congenital infection. Recent data bring out that its transmission can be
      prevented through treatment of infected women before they become pregnant. The
      role of parasite genotypes and host genetic factors in parasite transmission and
      development of infection in foetuses/neonates has to be more investigated in
      order to better estimate the risk factors and impact on health of congenital
      infection with T. cruzi.

PMID- 25760450
TI  - A nuclear ribosomal DNA pseudogene in triatomines opens a new research field of
      fundamental and applied implications in Chagas disease.
AB  - A pseudogene, designated as "ps(5.8S+ITS-2)", paralogous to the 5.8S gene and
      internal transcribed spacer (ITS)-2 of the nuclear ribosomal DNA (rDNA), has been
      recently found in many triatomine species distributed throughout North America,
      Central America and northern South America. Among characteristics used as
      criteria for pseudogene verification, secondary structures and free energy are
      highlighted, showing a lower fit between minimum free energy, partition function
      and centroid structures, although in given cases the fit only appeared to be
      slightly lower. The unique characteristics of "ps(5.8S+ITS-2)" as a processed or
      retrotransposed pseudogenic unit of the ghost type are reviewed, with emphasis on
      its potential functionality compared to the functionality of genes and spacers of
      the normal rDNA operon. Besides the technical problem of the risk for erroneous
      sequence results, the usefulness of "ps(5.8S+ITS-2)" for specimen classification,
      phylogenetic analyses and systematic/taxonomic studies should be highlighted,
      based on consistence and retention index values, which in pseudogenic sequence
      trees were higher than in functional sequence trees. Additionally,
      intraindividual, interpopulational and interspecific differences in pseudogene
      amount and the fact that it is a pseudogene in the nuclear rDNA suggests a
      potential relationships with fitness, behaviour and adaptability of triatomine
      vectors and consequently its potential utility in Chagas disease epidemiology and
      control.

PMID- 25760454
TI  - High-density metallic nanogap arrays for the sensitive detection of single-walled
      carbon nanotube thin films.
AB  - We have investigated the extraordinary optical transmission of terahertz waves
      through an array of nanogaps with varying dimensions and periodicities, and used
      this platform to demonstrate terahertz sensing of a thin film of single-walled
      carbon nanotubes. We have used atomic layer lithography to fabricate periodic
      arrays of nanogap loops that have a gap size of 2 nm and a loop length of 100 MUm
      (aspect ratio of 50,000). These sub-mm-scale loops of nanogaps can sustain
      terahertz electromagnetic resonances along the contour. We have characterized the
      transmission of terahertz waves through the nanogap arrays and investigated the
      influence of inter-gap electromagnetic coupling as the array periodicity shrinks
      from 100 MUm to 4 MUm. While the gaps occupy only 0.1% of the surface area, we
      have measured an amplitude (|E|) transmittance of over 50% due to the strong and
      broadband field enhancement inside the nanogaps. The absolute transmission
      through the 2 nm gaps along the rectangular loops can be boosted up to 25%, while
      it is only 1% for annular gaps with the same perimeter. Furthermore, the
      extremely tight field confinement and strong field enhancement near the 2 nm gap
      lead to 43% extinction of THz waves in a 10 nm-thick film of single-walled carbon
      nanotubes over the gaps. On the other hand, THz extinction by the same nanotube
      film on a bare glass substrate is only 2%. These nanogaps pave the way toward
      developing sensitive terahertz detectors for biological and chemical targets.

PMID- 25760455
TI  - Matrine induces mitochondrial apoptosis in cisplatin-resistant non-small cell
      lung cancer cells via suppression of beta-catenin/survivin signaling.
AB  - Matrine is an alkaloid isolated from Sophora flavescens and shows anticancer
      activities. The present study was carried out to determine the cytotoxic effects
      of matrine on cisplatin-resistant non-small cell lung cancer (NSCLC) cells and
      the associated molecular mechanisms. Parental and cisplatin-resistant A549 and
      H460 NSCLC cells were treated with 1 or 2 g/l of matrine for 48 h, and cell
      viability and apoptosis were assessed. beta-catenin-mediated transcriptional
      activity, mitochondrial membrane potential (DeltaPsim) changes, activation of
      caspases, and survivin expression were examined. The effect of overexpression of
      survivin on the anticancer activity of matrine was investigated. Compared to the
      parental cells, cisplatin-resistant NSCLC cells showed increased beta-catenin
      transcriptional activity. Matrine treatment resulted in a significant reduction
      in beta-catenin activation and survivin expression in the cisplatin-resistant
      cells. Matrine caused apoptotic death in the cisplatin-resistant NSCLC cells,
      coupled with loss of DeltaPsim and activation of caspase-9 and -3. Matrine
      induced apoptosis of the cisplatin-resistant NSCLC cells was significantly
      reversed by overexpression of survivin. In conclusion, matrine exposure induces
      mitochondrial apoptosis in cisplatin-resistant NSCLC cells, which is largely
      mediated through inactivation of beta-catenin/survivin signaling. Further
      investigation of the therapeutic benefit of matrine in overcoming cisplatin
      resistance in NSCLC is warranted.

PMID- 25760456
TI  - Circumcision as a primary HIV preventive: extrapolating from the available data.
AB  - Billions of dollars to circumcise millions of African males as an HIV infection
      prevention have been sought, yet the effectiveness of circumcision has not been
      demonstrated. Data from 109 populations comparing HIV prevalence and incidence in
      men based on circumcision status were evaluated using meta-regression. The impact
      on the association between circumcision and HIV incidence/prevalence of the HIV
      risk profile of the population, the circumcision rates within the population and
      whether the population was in Africa were assessed. No significant difference in
      the risk of HIV infection based on the circumcision status was seen in general
      populations. Studies of high-risk populations and populations with a higher
      prevalence of male circumcision reported significantly greater odds ratios (odds
      of intact man having HIV) (p < .0001). When adjusted for the impact of a high
      risk population and the circumcision rate of the population, the baseline odds
      ratio was 0.78 (95% CI = 0.56-1.09). No consistent association between presence
      of HIV infection and circumcision status of adult males in general populations
      was found. When adjusted for other factors, having a foreskin was not a
      significant risk factor. This undermines the justification for using circumcision
      as a primary preventive for HIV infection. 

PMID- 25760457
TI  - Distinct Cutaneous Manifestations and Cold-Induced Leukocyte Activation
      Associated With PLCG2 Mutations.
AB  - IMPORTANCE: PLCG2-associated antibody deficiency and immune dysregulation (PLAID)
      is a newly characterized immunodeficiency syndrome associated with distinct
      cutaneous features. Awareness of the cutaneous skin findings associated with
      PLAID may facilitate diagnosis and improve patient care. OBJECTIVES: To
      characterize the cutaneous manifestations of PLAID and identify potential
      cellular mechanisms of the disease. DESIGN, SETTING, AND PARTICIPANTS: In this
      retrospective analysis of patients with PLAID and PLAID-like disease evaluated at
      the National Institutes of Health from January 1, 2005, through December 31,
      2014, patients with deletions in PLCG2 leading to PLAID and patients with PLAID
      like disease for whom a PLAID mutation was not identified were studied. MAIN
      OUTCOMES AND MEASURES: Characterization of cutaneous manifestations of PLAID and
      PLAID-like disease and analysis of PLAID immune cell activation. RESULTS: Among
      36 patients with PLAID and PLAID-like phenotypes, all of whom had evaporative
      cold urticaria, 8 patients had a history of unique neonatal-onset ulcerative and
      cutaneous lesions in cold-sensitive regions of the body. Granulomatous skin
      lesions sparing warm regions (eg, flexural surfaces and skinfolds) were
      identified in 4 patients. Neutrophils and monocytes from patients with PLAID
      exhibited enhanced baseline activation in vitro, which was potentiated by ambient
      temperature exposure. CONCLUSIONS AND RELEVANCE: Collectively, these findings
      suggest that early identification of neonatal lesions may help in the diagnosis
      of PLAID and that leukocyte hyperactivation may underlie cutaneous lesions in
      patients with PLAID. Further characterization of mechanisms underlying leukocyte
      hyperactivation may contribute to the fundamental understanding of granuloma
      formation.

PMID- 25760458
TI  - A serine protease isolated from the bristles of the Amazonic caterpillar,
      Premolis semirufa, is a potent complement system activator.
AB  - BACKGROUND: The caterpillar of the moth Premolis semirufa, commonly named
      pararama, is found in the Brazilian Amazon region. Accidental contact with the
      caterpillar bristles causes an intense itching sensation, followed by symptoms of
      an acute inflammation, which last for three to seven days after the first
      incident. After multiple accidents a chronic inflammatory reaction, called
      "Pararamose", characterized by articular synovial membrane thickening with joint
      deformities common to chronic synovitis, frequently occurs. Although complement
      mediated inflammation may aid the host defense, inappropriate or excessive
      activation of the complement system and generation of anaphylatoxins can lead to
      inflammatory disorder and pathologies. The aim of the present study was to
      evaluate, in vitro, whether the Premolis semirufa's bristles extract could
      interfere with the human complement system. RESULTS: The bristles extract was
      able to inhibit the haemolytic activity of the alternative pathway, as well as
      the activation of the lectin pathway, but had no effect on the classical pathway,
      and this inhibition seemed to be caused by activation and consumption of
      complement components. The extract induced the production of significant amounts
      of all three anaphylatoxins, C3a, C4a and C5a, promoted direct cleavage of C3, C4
      and C5 and induced a significant generation of terminal complement complexes in
      normal human serum. By using molecular exclusion chromatography, a serine
      protease of 82 kDa, which activates complement, was isolated from P. semirufa
      bristles extract. The protease, named here as Ps82, reduced the haemolytic
      activity of the alternative and classical pathways and inhibited the lectin
      pathway. In addition, Ps82 induced the cleavage of C3, C4 and C5 and the
      generation of C3a and C4a in normal human serum and it was capable to cleave
      human purified C5 and generate C5a. The use of Phenanthroline, metalloprotease
      inhibitor, in the reactions did not significantly interfere with the activity of
      the Ps82, whereas the presence of PMSF, serine protease inhibitor, totally
      blocked the activity. CONCLUSION: These data show that a serine protease present
      in the Premolis semirufa's bristles extract has the ability to activate the
      complement system, which may contribute to the inflammatory process presented in
      humans after envenomation.

PMID- 25760459
TI  - Stem- and progenitor cell proliferation in the dentate gyrus of the reeler mouse.
AB  - Adult hippocampal neurogenesis has been implicated in hippocampus-dependent
      learning and memory. Furthermore, the decline of neurogenesis accompanying aging
      could be involved in age-related cognitive deficits. It is believed that the
      neural stem cell niche comprises a specialized microenvironment regulating stem
      cell activation and maintenance. However, little is known about the significance
      of the extracellular matrix in controlling adult stem cells. Reelin is a large
      glycoprotein of the extracelluar matrix known to be of crucial importance for
      neuronal migration. Here, we examined the local interrelation between Reelin
      expressing interneurons and putative hippocampal stem cells and investigated the
      effects of Reelin deficiency on stem cell and progenitor cell proliferation.
      Reelin-positive cells are found in close vicinity to putative stem cell
      processes, which would allow for stem cell regulation by Reelin. We investigated
      the proliferation of stem cells in the Reelin-deficient reeler hippocampus by
      Ki67 labeling and found a strong reduction of mitotic cells. A detailed analysis
      of dividing Type 1, type 2 and type 3 cells indicated that once a stem cell is
      recruited for proliferation, the progression to the next progenitor stage as well
      as the number of mitotic cycles is not altered in reeler. Our data point to a
      role for Reelin in either regulating stem cell quiescence or maintenance. 

PMID- 25760460
TI  - Effect of laying sequence on egg mercury in captive zebra finches: an
      interpretation considering individual variation.
AB  - Bird eggs are used widely as noninvasive bioindicators for environmental mercury
      availability. Previous studies, however, have found varying relationships between
      laying sequence and egg mercury concentrations. Some studies have reported that
      the mercury concentration was higher in first-laid eggs or declined across the
      laying sequence, whereas in other studies mercury concentration was not related
      to egg order. Approximately 300 eggs (61 clutches) were collected from captive
      zebra finches dosed throughout their reproductive lives with methylmercury (0.3
      MUg/g, 0.6 MUg/g, 1.2 MUg/g, or 2.4 MUg/g wet wt in diet); the total mercury
      concentration (mean +/- standard deviation [SD] dry wt basis) of their eggs was
      7.03 +/- 1.38 MUg/g, 14.15 +/- 2.52 MUg/g, 26.85 +/- 5.85 MUg/g, and 49.76 +/-
      10.37 MUg/g, respectively (equivalent to fresh wt egg mercury concentrations of
      1.24 MUg/g, 2.50 MUg/g, 4.74 MUg/g, and 8.79 MUg/g). The authors observed a
      significant decrease in the mercury concentration of successive eggs when
      compared with the first egg and notable variation between clutches within
      treatments. The mercury level of individual females within and among treatments
      did not alter this relationship. Based on the results, sampling of a single egg
      in each clutch from any position in the laying sequence is sufficient for
      purposes of population risk assessment, but it is not recommended as a proxy for
      individual female exposure or as an estimate of average mercury level within the
      clutch.

PMID- 25760461
TI  - Reactivity of transition-metal borylene complexes: recent advances in B-C and B-B
      bond formation via borylene ligand coupling.
AB  - Terminal borylene complexes of group 6-10 metals have been prepared through a
      number of synthetic strategies, displaying a wide structural diversity with
      numerous coordination modes of the borylene ligand [:BR]. Earlier, amino
      substituted borylenes were found to serve as borylene ligand transfer reagents to
      a range of organic and organometallic substrates. In contrast, aryl- and alkyl
      substituted borylenes display metathesis behavior when combined with ketones.
      Recent studies on these complexes revealed new reactivity patterns involving
      borylene-borylene and carbonyl-borylene ligand coupling. Herein a brief account
      on the recent progress of these borylene ligand coupling reactions made in our
      laboratories is provided. These reactions offer unprecedented alternative methods
      for electron-precise B-B and B-C bond formation. 

PMID- 25760463
TI  - Early development of gonads in Muscovy duck embryos.
AB  - Characteristics of gonadal development were investigated in Muscovy duck embryos
      at various embryonic ages. Hematoxylin-Eosin and periodic acid-Schiff staining
      were used to identify primordial germ cells, oogonia and sustentacular cells.
      Gene specific primers were designed based on conserved regions of duck
      antimullerian hormone (AMH), oestrogen receptor-alpha (ESR-alpha), doublesex and
      Mab-3 related transcription factor-1(DMRT1) and W chromosome protein kinase C
      inhibitor/interacting gene (WPKCI). Quantitative real-time polymerase chain
      reaction was used to characterise gene expression during gonad development in
      Muscovy duck embryos. Histology indicated that ovarian and testicular cells of
      Muscovy duck embryos developed on d 9 and 10. Immunohistochemistry showed that
      mouse vasa homologue-positive cells as well as Glial cell line-derived
      neurotrophic factor-positive cells increased significantly more in females than
      in males between d 9 and 10. AMH and ESR-alpha expression increased significantly
      during early development. DMRT1 acts prior to and during testis differentiation
      whereas WPKCI was expressed actively in the female Muscovy duck embryo before the
      onset of gonadal differentiation. Gonad development in Muscovy duck embryo was
      associated with several genes that were expressed before morphological features
      appear and were gender specific. 

PMID- 25760462
TI  - Expression pattern and subcellular localization of the ovate protein family in
      rice.
AB  - The Arabidopsis ovate family proteins (AtOFPs) have been shown to function as
      transcriptional repressors and regulate multiple aspects of plant growth and
      development. There are 31 genes that encode the full-length OVATE-domain
      containing proteins in the rice genome. In this study, the gene structure
      analysis revealed that OsOFPs are intron poor. Phylogenetic analysis suggested
      that OVATE proteins from rice, Arabidopsis and tomato can be divided into 4
      groups (I-IV). Real-time quantitative polymerase chain reaction (RT-qPCR)
      analysis identified OsOFPs with different tissue-specific expression patterns at
      all stages of development in the rice plant. Interestingly, nearly half of the
      total number of OsOFP family was more highly expressed during the seed
      developmental stage. In addition, seed developmental cis-elements were found in
      the promoter region of the OsOFPs. Subcellular localization analysis revealed
      that YFP-OsOFP fusion proteins predominantly localized in the nucleus. Our
      results suggest that OsOFPs may act as regulatory proteins and play pivotal roles
      in the growth and development of rice. 

PMID- 25760465
TI  - Juvenile migraine and allodynia: results of a retrospective study.
AB  - BACKGROUND: There are only 2 small sample studies investigating allodynia in the
      pediatric population. The aim of this study was to evaluate the frequency of
      allodynia during cephalalgic attacks in a juvenile population with primary
      headaches and its association with other symptoms of migraine. METHODS: We
      reviewed all medical records of patients with primary headache consecutively seen
      during a 2-year period. Frequency of allodynia was evaluated, by means of a
      questionnaire, consisting of 6 questions (for example: Do you avoid touching your
      head when you have a migraine attack?). RESULTS: Two hundred thirty children
      suffering from primary headache were seen during the study period. Two hundred
      two children were affected by migraine, 28 (12.2%) by other primary headaches.
      Migraineurs significantly more frequently complained of allodynia compared to
      other primary headaches (37% vs 0%). At multivariate analysis, allodynia was
      significantly associated with pain aggravated by physical activity (adjusted odds
      ratio [ORa ] 2.0, 95% confidence interval [CI] 1.0, 3.8), phonophobia (ORa 2.3,
      95% CI 1.0, 5.1), and nausea (ORa 1.9, 95% CI 1.0, 3.7). CONCLUSION: According to
      our data, allodynia is common during pediatric migraine attacks. The association
      between allodynia and physical activity, nausea and phonophobia are supported by
      studies on adult population and suggests specific physiopathological mechanisms.

PMID- 25760466
TI  - The qualitative problem of major quotation errors, as illustrated by 10 different
      examples in the headache literature.
AB  - There are two types of errors when references are used in the scientific
      literature: citation errors and quotation errors, and these errors have in
      reviews mainly been evaluated quantitatively. Quotation errors are the major
      problem, and 1 review reported 6% major quotation errors. The objective of this
      listing of quotation errors is to illustrate by qualitative analysis of different
      types of 10 major quotation errors how and possibly why authors misquote
      references. The author selected for review the first 10 different consecutive
      major quotation errors encountered from his reading of the headache literature.
      The characteristics of the 10 quotation errors ranged considerably. Thus, in a
      review of migraine therapy in a very prestigious medical journal, the superiority
      of a new treatment (sumatriptan) vs an old treatment (aspirin plus
      metoclopramide) was claimed despite no significant difference for the primary
      efficacy measure in the trial. One author, in a scientific debate, referred to
      the lack of dilation of the middle meningeal artery in spontaneous migraine
      despite the fact that only 1 migraine attack was studied. The possibility for
      creative major quotation errors in the medical literature is most likely
      infinite. Qualitative evaluations, as the present, of major quotation errors will
      hopefully result in more general awareness of quotation problems in the medical
      literature. Even if the final responsibility for correct use of quotations is
      with the authors, the referees, the experts with the knowledge needed to spot
      quotation errors, should be more involved in ensuring correct and fair use of
      references. Finally, this paper suggests that major misleading quotations, if
      pointed out by readers of the journal, should, as a rule, be corrected by way of
      an erratum statement. 

PMID- 25760469
TI  - Cu-Catalyzed selective cascade sp(3) C-H bond oxidative functionalization towards
      isoxazoline derivatives.
AB  - The first Cu-catalyzed cascade sp(3) C-H bond oxidative functionalization of the
      2-ethylazaarenes has been developed. The two different sp(3) C-H bonds in 2
      ethylazaarenes are selectively oxidized and four new types of bonds (C=O, C=N, C
      C, C-O) are constructed in one operation. Starting from the simple substrates and
      cheap nitro source, this reaction provides an efficient approach to produce new
      kinds of isoxazolines.

PMID- 25760468
TI  - Theoretical investigation on the glycan-binding specificity of Agrocybe
      cylindracea galectin using molecular modeling and molecular dynamics simulation
      studies.
AB  - Galectins are beta-galactoside binding proteins which have the ability to serve
      as potent antitumor, cancer biomarker, and induce tumor cell apoptosis. Agrocybe
      cylindracea galectin (ACG) is a fungal galectin which specifically recognizes
      alpha(2,3)-linked sialyllactose at the cell surface that plays extensive roles in
      the biological recognition processes. To investigate the change in glycan-binding
      specificity upon mutations, single point and double point site-directed in silico
      mutations are performed at the binding pocket of ACG. Molecular dynamics (MD)
      simulation studies are carried out for the wild-type (ACG) and single point
      (ACG1) and double point (ACG2) mutated ACGs to investigate the dynamics of
      substituted mutants and their interactions with the receptor sialyllactose.
      Plausible binding modes are proposed for galectin-sialylglycan complexes based on
      the analysis of hydrogen bonding interactions, total pair-wise interaction energy
      between the interacting binding site residues and sialyllactose and binding free
      energy of the complexes using molecular mechanics-Poisson-Boltzmann surface area.
      Our result shows that high contribution to the binding in different modes is due
      to the direct and water-mediated hydrogen bonds. The binding specificity of
      double point mutant Y59R/N140Q of ACG2 is found to be high, and it has 26 direct
      and water-mediated hydrogen bonds with a relatively low-binding free energy of 
      47.52 +/- 5.2 kcal/mol. We also observe that the substituted mutant Arg59 is
      crucial for glycan-binding and for the preference of alpha(2,3)-linked
      sialyllactose at the binding pocket of ACG2 galectin. When compared with the wild
      type and single point mutant, the double point mutant exhibits enhanced affinity
      towards alpha(2,3)-linked sialyllactose, which can be effectively used as a model
      for biological cell marker in cancer therapeutics.

PMID- 25760470
TI  - MMPIP, an mGluR7-selective negative allosteric modulator, alleviates pain and
      normalizes affective and cognitive behavior in neuropathic mice.
AB  - This study investigated the effects of a single administration of 6-(4
      methoxyphenyl)-5-methyl-3-pyridinyl-4-isoxazolo[4,5-c]pyridin-4(5H)-one (MMPIP),
      a negative allosteric modulator (NAM) of metabotropic glutamate receptor 7
      (mGluR7), on pain and on affective and cognitive behavior in neuropathic mice.
      The activity of pyramidal neurons in the prelimbic cortex (PLC), which respond to
      stimulation of the basolateral amygdala (BLA) with either excitation or
      inhibition, was also investigated. The spared nerve injury (SNI) of the sciatic
      nerve induced, 14 days after surgery, thermal hyperalgesia and mechanical
      allodynia, reduced open-arm choice in the elevated plus-maze, increased time of
      immobility in the tail suspension, and increased digging and burying in the
      marble burying test. Cognitive performance was also significantly compromised in
      the SNI mice. Spared nerve injury induced phenotypic changes on pyramidal neurons
      of the PLC; excitatory responses increased, whereas inhibitory responses
      decreased after BLA stimulation. mGluR7 expression, mainly associated with
      vesicular glutamate transporter, increased in the hippocampus and decreased in
      the BLA, PLC, and dorsal raphe in SNI mice. MMPIP increased thermal and
      mechanical thresholds and open-arm choice. It reduced the immobility in the tail
      suspension test and the number of marbles buried and of digging events in the
      marble burying test. MMPIP also improved cognitive performance and restored the
      balance between excitatory and inhibitory responses of PLC neurons in SNI mice. 7
      hydroxy-3-(4-iodophenoxy)-4H-chromen-4-one, XAP044, another selective mGluR7 NAM,
      reproduced the effects of MMPIP on thermal hyperalgesia, mechanical allodynia,
      tail suspension, and marble burying test. Altogether, these findings show that
      mGluR7 NAMs reduce pain responses and affective/cognitive impairments in
      neuropathic pain conditions. 

PMID- 25760471
TI  - The prevalence of problem opioid use in patients receiving chronic opioid
      therapy: computer-assisted review of electronic health record clinical notes.
AB  - To estimate the prevalence of problem opioid use, we used natural language
      processing (NLP) techniques to identify clinical notes containing text indicating
      problem opioid use from over 8 million electronic health records (EHRs) of 22,142
      adult patients receiving chronic opioid therapy (COT) within Group Health clinics
      from 2006 to 2012. Computer-assisted manual review of NLP-identified clinical
      notes was then used to identify patients with problem opioid use (overuse,
      misuse, or abuse) according to the study criteria. These methods identified 9.4%
      of patients receiving COT as having problem opioid use documented during the
      study period. An additional 4.1% of COT patients had an International
      Classification of Disease, version 9 (ICD-9) diagnosis without NLP-identified
      problem opioid use. Agreement between the NLP methods and ICD-9 coding was
      moderate (kappa = 0.61). Over one-third of the NLP-positive patients did not have
      an ICD-9 diagnostic code for opioid abuse or dependence. We used structured EHR
      data to identify 14 risk indicators for problem opioid use. Forty-seven percent
      of the COT patients had 3 or more risk indicators. The prevalence of problem
      opioid use was 9.6% among patients with 3 to 4 risk indicators, 26.6% among those
      with 5 to 6 risk indicators, and 55.04% among those with 7 or more risk
      indicators. Higher rates of problem opioid use were observed among young COT
      patients, patients who sustained opioid use for more than 4 quarters, and
      patients who received higher opioid doses. Methods used in this study provide a
      promising approach to efficiently identify clinically recognized problem opioid
      use documented in EHRs of large patient populations. Computer-assisted manual
      review of EHR clinical notes found a rate of problem opioid use of 9.4% among
      22,142 COT patients over 7 years. 

PMID- 25760473
TI  - How does pain lead to disability? A systematic review and meta-analysis of
      mediation studies in people with back and neck pain.
AB  - Disability is an important outcome from a clinical and public health perspective.
      However, it is unclear how disability develops in people with low back pain or
      neck pain. More specifically, the mechanisms by which pain leads to disability
      are not well understood. Mediation analysis is a way of investigating these
      mechanisms by examining the extent to which an intermediate variable explains the
      effect of an exposure on an outcome. This systematic review and meta-analysis
      aimed to identify and examine the extent to which putative mediators explain the
      effect of pain on disability in people with low back pain or neck pain. Five
      electronic databases were searched. We found 12 studies (N = 2961) that examined
      how pain leads to disability with mediation analysis. Standardized regression
      coefficients (beta) of the indirect and total paths were pooled. We found
      evidence to show that self-efficacy (beta = 0.23, 95% confidence interval [CI] =
      0.10 to 0.34), psychological distress (beta = 0.10, 95% CI = 0.01 to 0.18), and
      fear (beta = 0.08, 95% CI = 0.01 to 0.14) mediated the relationship between pain
      and disability, but catastrophizing did not (beta = 0.07, 95% CI = -0.06 to
      0.19). The methodological quality of these studies was low, and we highlight
      potential areas for development. Nonetheless, the results suggest that there are
      significant mediating effects of self-efficacy, psychological distress, and fear,
      which underpins the direct targeting of these constructs in treatment. 

PMID- 25760474
TI  - Differential contributions of A- and C-nociceptors to primary and secondary
      inflammatory hypersensitivity in the rat.
AB  - Primary hyperalgesia is characterized by increased responsiveness to both heat
      and mechanical stimulation in the area of injury. By contrast, secondary
      hyperalgesia is generally associated with increased responses to mechanical but
      not heat stimuli. We tested the hypothesis that sensitization in secondary
      hyperalgesia is dependent on the class of peripheral nociceptor (C- or A
      nociceptor) rather than the modality of stimulation (mechanical vs heat). A- and
      C-nociceptors were selectively activated using contact heat ramps applied to the
      hind paw dorsum in animals with hind paw inflammation (primary hyperalgesia) and
      knee inflammatory arthritis (secondary hyperalgesia). Sensitization to A- and C
      nociceptor activation in primary and secondary hyperalgesia was assessed by
      reflex withdrawal thresholds and by Fos immunocytochemistry in the dorsal horn of
      the spinal cord, as an index of neuronal activation. In primary hyperalgesia,
      only C-nociceptor-evoked withdrawal reflexes were sensitized. This was associated
      with increased spinal lamina I neuronal activation to both A- and C-nociceptor
      activation. Fos-like immunoreactivity (FLI) was unchanged in other dorsal horn
      laminae. In secondary hyperalgesia, only A-nociceptor-evoked withdrawal reflexes
      were sensitized, and FLI was increased in both superficial and deep dorsal
      laminae. Neurons in the superficial dorsal horn receive and process nociceptor
      inputs from the area of primary hyperalgesia, resulting in functional
      sensitization to C-nociceptive inputs. In inflammatory arthritis, secondary
      hyperalgesia is evoked by A-nociceptor thermal stimulation, suggesting that
      secondary hyperalgesia is A-nociceptor, rather than stimulus modality (mechanical
      vs thermal), dependent. Fos-like immunoreactivity evoked by A-nociceptor
      stimulation in secondary hyperalgesia suggests that the sensitization is
      underpinned by spinal neuronal sensitization in laminae I and IV/V. 

PMID- 25760476
TI  - Motivation, broadly construed, matters.

PMID- 25760475
TI  - Transplant-mediated enhancement of spinal cord GABAergic inhibition reverses
      paclitaxel-induced mechanical and heat hypersensitivity.
AB  - Decreased spinal cord GABAergic inhibition is a major contributor to the
      persistent neuropathic pain that can follow peripheral nerve injury. Recently, we
      reported that restoring spinal cord GABAergic signaling by intraspinal
      transplantation of cortical precursors of GABAergic interneurons from the
      embryonic medial ganglionic eminence (MGE) can reverse the mechanical
      hypersensitivity (allodynia) that characterizes a neuropathic pain model in the
      mouse. We show that MGE cell transplants are also effective against both the
      mechanical allodynia and the heat hyperalgesia produced in a paclitaxel-induced
      chemotherapy model of neuropathic pain. To test the necessity of GABA release by
      the transplants, we also studied the utility of transplanting MGE cells from mice
      with a deletion of VGAT, the vesicular GABA transporter. Transplants from these
      mice, in which GABA is synthesized but cannot be stored or released, had no
      effect on mechanical hypersensitivity or heat hyperalgesia in the paclitaxel
      model. Taken together, these results demonstrate the therapeutic potential of
      GABAergic precursor cell transplantation in diverse neuropathic pain models and
      support our contention that restoration of inhibitory controls through release of
      GABA from the transplants is their mode of action. 

PMID- 25760477
TI  - Curcumin triggers apoptosis via upregulation of Bax/Bcl-2 ratio and caspase
      activation in SW872 human adipocytes.
AB  - Induction of adipocyte apoptosis has been postulated as a novel strategy with
      which to treat obesity. The effects of curcumin, a polyphenol compound, on the
      apoptotic signaling pathway in SW872 adipocytes were investigated in the present
      study. The results showed that cell viability decreased following curcumin
      treatment in a time- and dose-dependent manner. The results from a single
      stranded DNA ELISA assay indicated that curcumin causes the number of apoptotic
      cells to increase in a concentration-dependent manner. In addition, curcumin
      treatment resulted in an increased expression of Bax, and a decrease in that of
      of Bcl-2, with a concomitant upregulation of the Bax/Bcl-2 ratio. Curcumin
      treatment also led to the release of cytochrome c from mitochondria into the
      cytosol. Similarly, caspase-dependent poly (ADP) ribose polymerase (PARP)
      cleavage by curcumin was observed in the current study. In conclusion the results
      indicate that curcumin is an effective therapeutic agent with which to induce
      apoptosis in adipocytes. This effect is, in part, mediated through the
      mitochondrial pathway, which involves upregulation of the Bax/Bcl-2 ratio,
      cytochrome c release, activation of caspase-3 and the cleavage of PARP.

PMID- 25760478
TI  - Upregulation of miR-155 in CD4(+) T Cells Promoted Th1 Bias in Patients With
      Unstable Angina.
AB  - An imbalance between T helper 1 (Th1) and T helper 2 (Th2) cells has been
      reported to increase plaque instability in patients with unstable angina (UA).
      MicroRNAs play a vital role in the differentiation of CD4(+) T cells. However,
      the role of microRNAs in regulation of Th1/Th2 balance in UA remains unclear. In
      this study, we aimed to elucidate microRNA expression profiles of circulating
      CD4(+) T cells in UA and to explore the function of microRNAs in the Th1/Th2
      balance. A total of 53 patients with UA and 31 control subjects without coronary
      artery disease were enrolled. Microarray analysis of the microRNA expression
      profiles of CD4(+) T cells revealed that miR-155 was the most significantly
      upregulated microRNA of the 451 differentially expressed microRNAs. The
      upregulation of miR-155 expression was positively correlated with the percentage
      of Th1 cells and interferon-gamma (IFN-gamma) levels in patients with UA. In
      addition, overexpression of miR-155 in human circulating CD4(+) T cells promoted
      Th1 differentiation. Further studies identified IFN-gamma receptor alpha chain
      (IFN-gamma Ralpha) mRNA as a direct and functional target of miR-155. A
      luciferase reporter assay verified that miR-155 directly targeted IFN-gamma
      Ralpha mRNA. Small-interfering RNA-mediated knockdown of IFN-gamma Ralpha mRNA
      showed effects similar to those of ectopic miR-155 expression. Thus, our study
      indicated that upregulation of miR-155 in circulating CD4(+) T cells in patients
      with UA promoted a shift in the Th1/Th2 balance toward Th1 dominance by
      repressing IFN-gamma Ralpha, which may subsequently enhance plaque instability.

PMID- 25760479
TI  - Asking the Stakeholders: Perspectives of Individuals With Aphasia, Their Family
      Members, and Physicians Regarding Communication in Medical Interactions.
AB  - PURPOSE: The purpose of this study was to explore the experiences of patients
      with aphasia, their family members, and physicians related to communication
      during medical interactions. METHOD: Face-to-face, semistructured interviews were
      conducted with 18 participants-6 patients with aphasia, 6 family members involved
      in patient care, and 6 practicing physicians. A qualitative description approach
      was used to collect and summarize narratives from participants' perspectives and
      experiences. Participants were asked about experiences with communication during
      medical interactions in which the family member accompanied the patient.
      Interviews were audio- and/or video-recorded, transcribed, and then coded to
      identify main themes. RESULTS: Patients and family members generally described
      their communication experiences as positive, yet all participants discussed
      challenges and frustrations. Three themes emerged: (a) patients and family
      members work as a team, (b) patients and family members want physicians to "just
      try" to communicate with the patient, and (c) physicians want to interact with
      patients but may not know how. CONCLUSIONS: Participants discussed the need for
      successful accommodation, or changing how one communicates, to help facilitate
      the patients' increased understanding and ability to express themselves. Over-
      and underaccommodation with communication were commonly reported as problems.
      Speech-language pathologists have a role to play in helping to improve
      communication during medical interactions. Implications for current speech
      language pathologist practice and future directions of research are discussed.

PMID- 25760480
TI  - Multicomponent analysis of fat- and water-soluble vitamins and auxiliary
      substances in multivitamin preparations by qNMR.
AB  - A nuclear magnetic resonance (NMR) spectroscopic method was tested to control 12
      vitamins and accompanying substances in multivitamin preparations. The limits of
      detection (LODs) and limits of quantification (LOQs) varied in the 9.0-77.0 mg/kg
      and in the 34.5-93.5 mg/kg range, respectively. The coefficients of variation
      (CVs) ranged between 0.9% and 12%. The (1)H NMR spectra showed linearity for the
      140-260 mg sample weight (R(2) > 0.918). The NMR spectra of multivitamin
      preparations showed the presence of different degradation products of ascorbic
      acid. The NMR method was applied to 13 different multivitamin preparations
      including tablets, capsules, and effervescent tablets with average recovery rates
      between 85% and 132%. A number of accompanying substances (citric acid, mannitol,
      saccharin, cyclamate, sum of steviol glycosides, and butylhydroxytoluene) were
      additionally identified and quantified. NMR was found to be suitable for the
      simultaneous qualitative measurement of water- and fat-soluble vitamins and
      accompanying substances and shows some promise for quantitative determination of
      at least 5 vitamins (B1, B3, B5, B6, and E) in multivitamin preparations. 

PMID- 25760481
TI  - Antiviral therapy in chronic hepatitis E: a systematic review.
AB  - Hepatitis E viral infection can lead to a chronic infection in immunocompromised
      patients, resulting in progressive liver disease and cirrhosis. Isolated cases
      have shown that treatment with ribavirin or pegylated interferon-alpha can result
      in viral eradication. This systematic review evaluated efficacy and safety of
      both treatments in chronic hepatitis E. A systematic literature search was
      performed on PubMed, Web of Science and clinicaltrials.gov for articles and
      abstracts. The keywords '"Hepatitis E" or HEV' AND 'ribavirin or Rebetol or
      Copegus' OR 'pegylated interferon OR peginterferon' were combined. The primary
      outcome was sustained viral response (SVR). Secondary endpoints include rapid
      viral response (RVR), relapse rates and side effects. Twenty-four studies matched
      our criteria, representing a total of 105 ribavirin-treated and 8 pegylated
      interferon-treated patients. The majority of patients had a solid organ
      transplant. Sixty-four per cent of ribavirin-treated patients achieved a SVR at 6
      months after treatment cessation compared to 2/8 peginterferon-treated patients.
      Ribavirin was relatively well tolerated with the main side effect being anaemia,
      requiring dose reduction in 28% of patients. Peginterferon leads to acute
      transplant rejection in 2/8 patients. Ribavirin monotherapy appears to be an
      effective and safe treatment in all immunocompromised patients with chronic
      hepatitis E. The use of pegylated interferon in transplant patients may lead to
      transplant rejection and is not recommended. Therefore, ribavirin should be the
      antiviral treatment of choice in chronic hepatitis E. 

PMID- 25760483
TI  - Bipedicled flap for the reconstruction of soft tissue defects of the Achilles
      tendon.
AB  - Soft tissue defects exposing the Achilles tendon are common in patients who have
      undergone trauma or in those with pressure ulcers associated with vascular
      diseases. The purpose of this article was to present our experience of 11
      patients who underwent reconstruction of soft tissue defects of the Achilles
      tendon using bipedicled fasciocutaneous flaps. Between August 2008 and August
      2012, 11 patients were admitted to our hospital, presenting with soft tissue
      defects overlying the Achilles tendon. After adequate debridement, the 11
      patients underwent bipedicled fasciocutaneous flap placement to resurface the
      complex soft tissue defects and provide a gliding surface for the exposed
      Achilles tendon. The patients' age, comorbidity, etiology, defect size and
      location, wound culture, skin graft size, complications, surgery duration, and
      follow-up period were reviewed. The 11 fasciocutaneous bipedicled flaps survived
      completely, and the wounds healed satisfactorily at a mean follow-up period of
      20.9 months (range, 6-48 months). Only 1 flap was complicated with wound
      dehiscence and superficial necrosis of its lateral edge, which healed
      conservatively. The donor sites were covered with split-thickness skin grafts and
      healed well without complications. The bipedicled fasciocutaneous flap is a
      reliable flap for coverage of defects overlying the Achilles tendon, especially
      in patients with vascular problems and/or elderly patients. The ease of handling,
      short operative time, and early recovery of mobilization function are of great
      benefit to patients. Thus, the bipedicled fasciocutaneous flap can be a valuable
      alternative for defect reconstructions overlying the Achilles tendon, with
      satisfactory results both functionally and cosmetically. 

PMID- 25760482
TI  - MicroRNA-146b-5p inhibits the growth of gallbladder carcinoma by targeting
      epidermal growth factor receptor.
AB  - Gallbladder cancer (GBC) is the most common and aggressive type of biliary tract
      cancer. The study of potential treatments for GBC has recently focused on
      microRNAs, a class of small non-coding RNAs, which post-transcriptionally
      regulate gene expression during various crucial cell processes. The present study
      aimed to investigate the role of microRNA-146b (miR-146b) in GBC. Human GBC
      tissue and adjacent normal gallbladder tissue sections were surgically removed
      and miR-146b-5p expression and the development and pathological characteristics
      of GBC were investigated. miR-146b-5p expression was reduced in GBC tissue
      compared with that in adjacent tissue, and a significant correlation was observed
      between miR-146b-5p expression levels and carcinoma size and development. miR
      146b-5p overexpression in the SGC-996 GBC cell line inhibited cell growth through
      enhanced apoptosis and G1 phase arrest. Furthermore, it was demonstrated that
      epidermal growth factor receptor (EGFR) was regulated directly by miR-146b-5p and
      was essential as a mediator of the biological effects of miR-146b-5p in GBC.
      Enforced expression of EGFR reversed the ability of miR-146b-5p to inhibit
      proliferation. In conclusion, the present study indicated that the mechanism of
      action of miR-146b-5p in GBC involves the regulation of EGFR expression.

PMID- 25760488
TI  - From organizational awareness to organizational competency in health care social
      work: the importance of formulating a "profession-in-environment" fit.
AB  - Today's health care environments require organizational competence as well as
      clinical skill. Economically driven business paradigms and the principles
      underlying the Patient Protection and Affordable Care Act of 2010 emphasize
      integrated, collaborative care delivered using transdisciplinary service models.
      Attention must be focused on achieving patient care goals while demonstrating an
      appreciation for the mission, priorities and operational constraints of the
      provider organization. The educational challenge is to cultivate the ability to
      negotiate "ideology" or ideal practice with the practical realities of health
      care provider environments without compromising professional ethics. Competently
      exercising such ability promotes a sound "profession-in-environment" fit and
      enhances the recognition of social work as a crucial patient care component. 

PMID- 25760487
TI  - A role for social workers in improving care setting transitions: a case study.
AB  - High 30-day readmission rates are a major burden to the American medical system.
      Much attention is on transitional care to decrease financial costs and improve
      patient outcomes. Social workers may be uniquely qualified to improve care
      transitions and have not previously been used in this role. We present a case
      study of an older, dually eligible Latina woman who received a social work-driven
      transition intervention that included in-home and telephone contacts. The patient
      was not readmitted during the six-month study period, mitigated her high pain
      levels, and engaged in social outings once again. These findings suggest the
      value of a social worker in a transitional care role. 

PMID- 25760489
TI  - Development of the Emergency Medical Services Role Identity Scale (EMS-RIS).
AB  - This article describes the development and validation of the theoretically
      grounded Emergency Medical Services Role Identity Scale (EMS-RIS), which measures
      four domains of EMS role identity. The EMS-RIS was developed using a mixed
      methods approach. Key informants informed item development and the scale was
      validated using a representative probability sample of EMS personnel. Factor
      analyses revealed a conceptually consistent, four-factor solution with sound
      psychometric properties as well as evidence of convergent and discriminant
      validities. Social workers work with EMS professionals in crisis settings and as
      their counselors when they are distressed. The EMS-RIS provides useful
      information for the assessment of and intervention with distressed EMS
      professionals, as well as how role identity may influence occupational stress. 

PMID- 25760490
TI  - Effect of enhanced psychosocial assessment on readmissions of patients with
      chronic obstructive pulmonary disease.
AB  - In 2015, the Patient Protection and Affordable Care Act of 2010 will mandate
      reduced Medicare reimbursements for hospitals with Chronic Obstructive Pulmonary
      Disease (COPD) readmissions that are higher than expected. Several studies
      identified social issues as a concern and possible contributor to readmissions.
      This study calculated readmission rates for patients with COPD following an
      enhanced psychosocial assessment. With 26 participants serving as their own
      historical controls, a paired t-test of the mean of admissions 90 days prior to
      the assessment and 90 days postassessment was conducted. The study group had a
      significantly lower number of readmissions in the 90 days postintervention. 

PMID- 25760491
TI  - Perceptions of the hospital ethical environment among hospital social workers in
      the United States.
AB  - Hospital social workers are in a unique context of practice, and one where the
      ethical environment has a profound influence on the ethical behavior. This study
      determined the ratings of ethical environment by hospital social workers in large
      nationwide sample. Correlates suggest by and compared to studies of ethical
      environment with nurses are explored. Positive ratings of the ethical environment
      are primarily associated with job satisfaction, as well as working in a
      centralized social work department and for a non-profit hospital. Religiosity and
      MSW education were not predictive. Implications and suggestions for managing the
      hospital ethical environment are provided. 

PMID- 25760492
TI  - Experiences of stigmatization and discrimination in accessing health services:
      voices of persons living with HIV in Ghana.
AB  - Drawing on Earnshaw and Chaudoir's HIV stigma framework, this study explored the
      experiences of persons living with HIV and AIDS regarding stigmatization and
      discrimination in accessing health services. Using a qualitative research
      methodology, 42 participants were purposively recruited during support group
      meetings of persons living with HIV and AIDS (PLWHA) at Amasaman in Accra, Ghana.
      Four focus group discussions (n = 22) and 10 in-depth interviews were conducted.
      Discussions and interviews were audio-taped, transcribed, and categorized based
      on the objectives of the study. The findings indicated that PLWHAs had knowledge
      of stigma that was experienced through enacted, anticipated, and internalized
      stigma mechanisms. Evidence showed that PLWHA did not experience stigma and
      discrimination when they accessed services at the Korle-Bu Teaching Hospital, the
      largest hospital in Ghana. However, the situation was different when they
      accessed services at other public health facilities. Based on the findings,
      implications are discussed for policy, social work, and public health practices. 

PMID- 25760493
TI  - Radiologic case study. Dialysis-related amyloidosis.
AB  - A 59-year-old woman presented with worsening bilateral hip pain for 6 months. She
      had been receiving hemodialysis for 12 years. 

PMID- 25760494
TI  - Median nerve superficial to the transverse carpal ligament.

PMID- 25760495
TI  - The orthopedic surgeon: can we turn out the same product in a shorter time frame
      and with less cost?

PMID- 25760496
TI  - Air physiogram: technique for visualization of the resected physis in
      percutaneous epiphysiodesis.
AB  - Obtaining an air physiogram improves visualization of the resected physis and
      allows the surgeon to assess whether a sufficient amount of growth plate has been
      removed during percutaneous drilling epiphysiodesis. From 2008 through 2011, the
      air physiogram technique was used in 37 percutaneous epiphysiodesis procedures
      about the knee (17 femora, 20 tibiae) in 31 children. Average follow-up was 41
      months (range, 19-70 months). Thirty-six of 37 limb segments achieved
      radiographic fusion after the initial procedure. One tibia appeared to be
      partially fused and underwent revision epiphysiodesis. At final follow-up, all
      limb segments had successful epiphysiodesis and showed radiographic evidence of
      fusion.

PMID- 25760498
TI  - Management of medial-sided knee injuries.
AB  - Medial collateral ligament injuries are common and are often associated with
      concomitant ligamentous, meniscus, and cartilage injuries. Orthopedic surgeons
      should be familiar with the outcomes of nonoperative and operative treatment of
      isolated and combined grade I, II, and III injuries. Special attention should be
      paid to identifying involvement of the posterior oblique ligament and capsule;
      lack of such attention may lead to failed nonoperative management. The authors
      present an overview of the treatment of medial-sided knee injuries, as well as 2
      cases demonstrating their preferred method of treating chronic medial-sided
      laxity and instability.

PMID- 25760497
TI  - Orthopedic surgery fellowships: the effects of interviewing and how residents
      establish a rank list.
AB  - The Orthopaedic Fellowship Match was established in 2008 to streamline and
      improve the process of matching residents and fellowships. The purpose of this
      study was to quantify the factors that affect the application process and to
      determine how residents establish a rank list. The Orthopaedic Fellowship Match
      has improved the ability of residents and programs to consider their options more
      carefully and to focus on finding the best match. However, this process
      introduces new factors for all parties involved to consider. The costs of the
      interview process and time away from service for residents may be larger than
      anticipated. Ultimately, residents value operative experience and staff members
      at a fellowship more than all other factors when selecting a fellowship.

PMID- 25760499
TI  - Femoroacetabular impingement: current concepts in diagnosis and treatment.
AB  - EDUCATIONAL OBJECTIVES: As a result of reading this article, physicians should be
      able to: 1. Identify the etiology of femoroacetabular impingement. 2. Assess
      femoroacetabular impingement on physical examination. 3. Recognize
      femoroacetabular impingement on imaging studies. 4. Discuss modern techniques to
      effectively treat femoroacetabular impingement, both open and arthroscopic.
      Femoroacetabular impingement (FAI) is a recently proposed concept describing
      abnormal anatomic relationships within the hip joint that may lead to articular
      damage. Impingement is caused by bony deformities or spatial malorientation of
      the femoral head-neck junction and/or the acetabulum. These abnormalities lead to
      pathologic contact and shearing forces at the acetabular labrum and cartilage
      during physiological hip motion. There is an increasing body of evidence that
      these forces lead to cartilage wear and eventual osteoarthritis. Treatment
      options for FAI are evolving rapidly. Although the gold standard remains open hip
      dislocation, arthroscopic techniques have shown significant promise. It is
      possible that early recognition and treatment of subtle deformity about the hip
      may reduce the rate of hip osteoarthritis in the future.

PMID- 25760500
TI  - Far cortical locking screws in distal femur fractures.
AB  - Distal femur fractures routinely heal by secondary bone healing, which relies on
      interfragmentary motion. Periarticular locking plates are commonly used for
      fixation in distal femur fractures but are associated with a high nonunion rate,
      likely due to the stiffness of the constructs. Far cortical locking (FCL) screws
      are designed to allow micromotion at the near cortex while maintaining purchase
      in only the far cortex. Although clinical data are limited, these screws have
      been shown in biomechanical studies to provide excellent interfragmentary motion,
      and animal models have shown increased callus formation compared with traditional
      locking screws. The purpose of this study was to examine the clinical effects
      that FCL screws have on healing in distal femur fractures treated with locked
      constructs. In this retrospective case series, 15 patients with a distal femur
      fracture treated with MotionLoc screws (Zimmer, Warsaw, Indiana) were analyzed.
      Serial radiographs were evaluated for callus presence and time to union. All
      fractures were either 33-A3 or 33-C2 according to the AO classification system,
      and 5 (33%) were open. Bone loss was recorded in 2 patients. There were no
      nonunions, and average time to union was 24 weeks. There were no implant
      failures, and all 5 open fractures, including the 2 with bone loss, healed
      without intervention. There was 1 reoperation due to painful hardware. Although
      this is a small case series, these results are promising. Far cortical locking
      screws may provide the answer to the high nonunion rate associated with distal
      femur fractures treated with traditional locked constructs.

PMID- 25760501
TI  - Effect of repeated manipulation on range of motion in patients with stiff total
      knee arthroplasty.
AB  - Although manipulation under anesthesia (MUA) has been considered effective first
      line treatment for stiff total knee arthroplasty (TKA), there is no consensus
      regarding the usefulness of repeated MUA. The purpose of this study was to
      investigate the usefulness of repeated MUA performed for patients in whom
      satisfactory range of motion (ROM) was not achieved by MUA. The authors
      retrospectively reviewed 15 patients who underwent repeated MUA after failure of
      initial MUA for stiff TKA. Demographic and ROM data were collected. A final ROM
      of less than 90 degrees  was considered a failed manipulation (failure group) and
      a final ROM of 90 degrees  or more was considered a successful manipulation
      (success group). Average pre-repeated MUA ROM (72.3 degrees +/-19.5 degrees )
      immediately improved to 112.3 degrees +/-9.7 degrees  (P<.001) in the operating
      room, and final ROM was 89.6 degrees +/-23.9 degrees , an overall gain of 17.3
      degrees  (P=.04). However, despite this overall ROM increase, a successful final
      ROM (90 degrees  or more) was achieved in approximately half of patients (7 of
      13; 54%). There were no significant differences in demographics between the
      success and failure groups, except that there was significantly less pre-TKA ROM
      in the failure group (P=.02). There were no complications related to either the
      first or the repeated MUA procedures. The findings of this study suggest that
      repeated MUA can improve overall ROM for stiff TKA. The success rate of repeated
      MUA was less than that of primary MUA; however, it is a useful treatment modality
      for stiff TKA. Decreased pre-TKA ROM appeared to be associated with poor outcomes
      after repeated MUA.

PMID- 25760502
TI  - Trabecular bone microarchitecture and characteristics in different regions of the
      glenoid.
AB  - Success of shoulder surgery depends on implant fixation to the glenoid trabecular
      bone. The purpose of this study was to evaluate the anatomic characteristics of
      the normal glenoid trabecular bone microarchitecture to help assist in implant
      design and provide data for finite element analyses. Eight cadavers without
      evidence of osteoarthritis were used. Glenoids were scanned with micro-computed
      tomography and then divided into lateral and medial, then superior, inferior,
      anterior, and posterior quadrants (8 total segments). Each segment was analyzed
      for total mineral density, bone volume fraction, structure model index, and
      trabecular thickness (Tb.Th), number (Tb.N), and separation. Bone volume fraction
      was significantly higher (P<.05) in the posterolateral (20.8%+/-4.5%) and
      posteromedial (18.6%+/-2.5%) regions. Both Tb.N and Tb.Th were also highest in
      the posterolateral (Tb.N, 1.74+/-0.374 mm; Tb.Th, 0.148+/-0.017 mm) and
      posteromedial (Tb.N, 1.49+/-0.401 mm; Tb.Th, 0.165+/-0.016 mm) regions.
      Trabecular separation was greatest in the superomedial segment (1.00+/-0.181 mm)
      and lowest in the posterolateral region (0.663+/-0.121 mm). For structural model
      index, both the posterolateral (0.314) and posteromedial (0.312) regions had
      lower values than the other regions. The posterior segment of the normal glenoid
      in both the lateral and medial regions has the highest density, which is
      attributed to the increased trabecular number and thickness with decreased
      separation. This increased density may be attributed to the posterior directed
      loading of the glenohumeral joint. The trabecular microarchitecture in the
      glenoid is plate-like, as indicated by the low structural model index.

PMID- 25760503
TI  - Agreement among ASES members on the AAOS Clinical Practice Guidelines.
AB  - The American Academy of Orthopaedic Surgeons (AAOS) has recently developed
      several clinical practice guidelines (CPG) involving upper extremity conditions.
      The purpose of the current study was to evaluate the practice patterns of members
      of the American Shoulder and Elbow Society (ASES) with regard to the CPGs. An e
      mail survey was sent to the 340 members of the ASES. The survey contained 40
      questions involving the subject matter of the 2 existing AAOS CPGs pertaining
      specifically to the shoulder: Optimizing the Management of Rotator Cuff Problems
      and the Treatment of Glenohumeral Joint Arthritis. Overall, 98 responses were
      obtained, for a response rate of 29%. Only 19 of 47 CPGs were not "inconclusive"
      and a recommendation was actually made. A majority (more than 50%) of surgeons
      agreed with 17 (90%) of 19 of these AAOS recommendations. A strong majority (more
      than 80%) adhered to 13 (68%) of 19 recommendations. There were 4 consensus
      recommendations, and more than 50% agreed with all of them. Of the 5 moderate
      recommendations, more than 50% agreed with 4 of them. There were 10 weak
      recommendations, and more than 50% of surgeons agreed with 9 of them. There was
      more than 80% agreement on 18 of 28 inconclusive recommendations. Although the
      AAOS CPGs are not meant to be fixed protocols, they are intended to unify
      treatment and/or diagnosis of common problems based on the best evidence
      available. Despite the majority of the AAOS CPG recommendations for rotator cuff
      problems and glenohumeral arthritis being inconclusive, most surgeons agree with
      most of the CPG recommendations.

PMID- 25760504
TI  - Patient-specific instrumentation does not improve accuracy in total knee
      arthroplasty.
AB  - Patient-specific instrumentation (PSI) has been introduced as a tool to increase
      the accuracy of total knee arthroplasty (TKA) compared with conventional
      instrumentation (CLI). However, previous studies have shown inconsistent results.
      The authors conducted a meta-analysis to compare the performance of PSI to CLI in
      TKA. PubMed, EMBASE, and Cochrane Central Register of Controlled Trials
      electronic databases were systematically searched to identify eligible trials
      published between 2000 and March 2014. Two reviewers independently assessed
      methodological quality according to the Cochrane Handbook. Subgroup analyses were
      performed based on the different study designs (randomized, controlled trial
      [RCT] vs non-randomized, controlled trial [non-RCT]), preoperative magnetic
      resonance imaging vs computed tomography, and systems of PSI to explore the
      source of heterogeneity. Fourteen studies (7 RCTs and 7 non-RCTs) involving 1906
      patients were included. There were no statistical differences with respect to the
      outliers of mechanical axis, coronal femoral component, sagittal femoral
      component, femoral component rotation, operative time, blood loss, and length of
      hospital stay between PSI and CLI groups. The number of outliers in coronal
      tibial components (odds ratio, 2.29; 95% confidence interval, 1.20 to 4.35;
      P=.01) and sagittal tibial components (odds ratio, 1.67; 95% confidence interval,
      1.16 to 2.42; P<.01) was significantly lower in the CLI group than in the PSI
      group. Based on the numbers available, the use of PSI compared with CLI was not
      likely to improve the accuracy of component alignment and treatment effects of
      TKA. Further high-quality RCTs are warranted to confirm the authors' results.

PMID- 25760505
TI  - Surgical indications for distal tibial epiphyseal fractures in children.
AB  - The goal of this study was to investigate the treatment methods and surgical
      indications of distal tibial epiphyseal fractures in children. Two hundred eighty
      six children with distal tibial epiphyseal fractures were included in the study.
      Among these patients, 202 were male and 84 were female. Mean age was 11.7 years.
      A retrospective study on the postoperative long-term complications and related
      risk factors was performed. Treatment methods were determined according to the
      distance of fracture displacement. A long-leg cast was applied after closed
      reduction for patients with primary fracture displacement less than 2 mm. For
      cases with more than 2 mm of fracture displacement, K-wire or screw fixation was
      performed. For patients with less than 2 mm of fracture displacement, closed
      reduction and internal fixation was performed. Open reduction was performed in
      patients with more than 2 mm of fracture displacement, even after closed
      reduction. Mean follow-up was 6.4 years. Premature physeal closure occurred in 42
      patients, and, among them, varus and valgus ankle deformities occurred in 16
      patients. Associated fibular fractures and cast immobilization after closed
      reduction for Salter-Harris type III and IV fractures were risk factors for
      premature physeal closure. It is not effective to determine the surgical
      procedure according to the distance of preoperative fracture displacement for
      improving the prognosis of distal tibial epiphyseal fractures in children.
      Conservative treatment should be performed for patients with Salter-Harris type I
      and II distal tibial epiphyseal fractures, and surgery should be performed in
      patients with Salter-Harris type III and IV distal tibial epiphyseal fractures to
      reduce the incidence of premature physeal closure.

PMID- 25760506
TI  - Low prevalence of isolated medial meniscal tears in young females with stable
      knees.
AB  - The information regarding isolated tears of the meniscus in stable knees (ie,
      without cruciate ligament tears), specifically in a younger population, is
      scarce. Although surgical treatment is preferred for young patients with meniscal
      tears, the diagnosis at this age may be misled by other sources of knee pain. The
      purpose of this study was to report on the prevalence and sex variance of
      isolated meniscal tears in a younger population based on arthroscopic findings.
      From a database of 2425 arthroscopic knee surgeries performed over a period of 6
      years, 591 patients (480 males and 111 females) younger than 40 years were
      included. Patients were divided into 5 age groups and subdivided according to
      their surgical findings. Measures included the prevalence of meniscal tears
      according to sex and age groups and also odds ratio calculations for the presence
      of meniscal tears. Of 591 arthroscopic surgeries in young patients with stable
      knees, only 6 females (vs 87 males) younger than 30 years had isolated medial
      meniscus tears. The number of stable knees without meniscal tear at arthroscopy
      in all age groups was relatively high. The odds ratio for having a medial
      meniscal tear was significantly higher in males. The results suggest a protective
      mechanism for isolated medial meniscal tears in younger females as opposed to
      other injuries of the knee. Isolated medial meniscus tears in stable knees are
      uncommon in females younger than 30 years; thus, young females with suspected
      tears should be reevaluated and treated conservatively before considering
      surgical solutions.

PMID- 25760507
TI  - Hyperbaric oxygen for stage I and II femoral head osteonecrosis.
AB  - Hyperbaric oxygen therapy is a suggested joint-preserving treatment for
      symptomatic early-stage osteonecrosis of the femoral head. Limited studies of
      this treatment have been published. The goal of this study was to evaluate the
      effectiveness of this treatment in a relatively large patient cohort. The authors
      reviewed the files of 68 patients with 78 symptomatic joints with Steinberg stage
      I and II osteonecrosis of the femoral head. All patients were treated with
      hyperbaric oxygen at the authors' medical health center. Pretreatment and
      immediate posttreatment magnetic resonance imaging (MRI) findings were compared.
      On follow-up, a telephone interview was conducted to determine the survival of
      the joint. Modified Harris Hip Score and Short Form 12 health survey (SF-12)
      questionnaires of the start of treatment and at follow-up were obtained and
      evaluated for statistically significant differences. Half of the joints were
      stage 1 and half were stage II. Seventy-four joints underwent both pre- and
      posttreatment MRI. Eighty-eight percent of joints showed improvement
      posttreatment. On follow-up at a mean of 11.1+/-5.1 years, 54 patients (58
      joints) were located and answered the questionnaires. At the time of follow-up,
      93% of the joints survived. Mean Harris Hip Score improved from 21 to 81
      (P<.0001), the mean physical component of the SF-12 improved from 24 to 46
      (P<.0001), and the mean mental component of the SF-12 improved from 54 to 59
      (P<.0001). The authors concluded that hyperbaric oxygen treatment is effective in
      preserving the hip joint in stage I and II osteonecrosis of the femoral head.

PMID- 25760508
TI  - Standard versus high-flexion posterior stabilized total knee prostheses.
AB  - This meta-analysis compared clinical outcomes between standard and high-flexion
      posterior-stabilized total knee prostheses to evaluate which type of total knee
      prosthesis was superior. Randomized, controlled trials published until October
      2013 comparing standard and high-flexion posterior-stabilized total knee
      prostheses were reviewed. Methodologic quality was assessed with the
      Physiotherapy Evidence Database scale. After data extraction, the authors
      compared results with fixed effects or random effects models, depending on the
      heterogeneity of the included studies. Eight randomized, controlled trials
      involving 660 patients met the predetermined inclusion criteria. No statistically
      significant differences between patients undergoing standard and high-flexion
      posterior-stabilized total knee prostheses were noted in postoperative range of
      motion (ROM) (weighted mean difference, -1.43; 95% confidence interval [CI], 
      4.52 to 1.67; P=.37); flexion angle (weighted mean difference, 0.54; 95% CI, 
      3.75 to 4.84; P=.80); Knee Society Score (weighted mean difference, 0.92; 95% CI,
      -0.64 to 2.48; P=.25); Hospital for Special Surgery knee score (weighted mean
      difference, 0.57; 95% CI, -0.42 to 1.55; P=.26); or Knee Society function score
      (weighted mean difference, 1.00; 95% CI, -1.49 to 3.49; P=.43). No statistical
      difference was found between the 2 prosthesis types in complications, involving
      21 cases in the standard group and 14 cases in the high-flexion group. The
      current findings confirm that high-flexion posterior-stabilized total knee
      prostheses are not superior to standard prostheses in terms of ROM, flexion
      angle, knee scores, or complications with 5 years or less of follow-up.

PMID- 25760509
TI  - Effect of decortications on union rate of tibial plating.
AB  - Tibial fracture is the most common long bone fracture. Because of the superficial
      location of the tibia, surgery is usually required for the treatment of fractures
      to achieve union. The goal of this study was to evaluate the effect of
      decortication on the faster union of fractures treated with compression plates.
      In this clinical trial, conducted from 2009 to 2013, 42 patients were randomly
      assigned to the decortication (20 patients) and control (22 patients) groups.
      Follow-up was performed every 2 weeks until union was achieved, and then patients
      were examined after 6 and 9 months for analysis of final union. Mean time to
      weight bearing with 2 crutches, weight bearing with 1 crutch, weight bearing with
      a cane, and complete weight bearing without pain in the control group (receiving
      only the compression plate) was 5.59, 7.50, 9.32, and 11.05 weeks, respectively.
      Mean time to weight bearing with 2 crutches, weight bearing with 1 crutch, weight
      bearing with a cane, and complete weight bearing without pain in the
      decortication group was 4.90, 6.35, 7.75, and 9.25 weeks, respectively. All 4
      values were significantly higher in the decortication group compared with the
      control group (P<.05). Erythema and signs of inflammation were significantly
      associated with decortication and were more common in the decortication group. No
      infection, broken plate, or nonunion occurred in either group. Because
      decortication had a significant effect on achieving union in nonunion fractures,
      it could be used to induce faster clinical union in acute tibial fractures.

PMID- 25760510
TI  - A novel technique using sensor-based technology to evaluate tibial tray rotation.
AB  - Rotational tibiofemoral congruency and centralized patellar tracking are critical
      technical factors that affect the postoperative success of total knee
      arthroplasty (TKA). Several techniques are used to position the femoral
      component, but there is no validated method for achieving the ideal rotational
      position of the tibial component. It has been suggested that referencing the
      midmedial third of the tibial tubercle intraoperatively mitigates positional
      outliers. This study used data collected from intraoperative sensors to quantify
      the variability associated with using the midmedial third of the tibial tubercle
      in 170 patients undergoing primary TKA. With the sensor-equipped trial insert in
      place, the knee was taken into extension and the location of the femoral condylar
      contact point on the articular surface of the tibial insert was displayed.
      Rotational adjustments of the tibial tray were evaluated in real time as the
      surgeon corrected tray malpositioning. The initial and final angles of tibial
      tray rotation were captured and recorded with intraoperative video feed. When
      referencing the tubercle, 53% of patients had asymmetric tibiofemoral congruency
      in extension. Of those patients, 68% had excessive internal rotation of the
      tibial tray relative to the femur and 32% had excessive external rotation. The
      average tibiofemoral incongruency deviated from a neutral position by 6 degrees 
      (range, 0.5 degrees -19.2 degrees ). Data from this evaluation suggest that use
      of the tibial tubercle to maximize tibiofemoral congruency is highly variable and
      inconsistent for confirming the final rotation of the tibial tray.

PMID- 25760511
TI  - Pulsed electromagnetic fields after rotator cuff repair: a randomized, controlled
      study.
AB  - The current study tested the hypothesis that the use of pulsed electromagnetic
      fields after rotator cuff repair is effective in the short term as an adjuvant
      treatment to reduce local inflammation, postoperative joint swelling, and
      recovery time, as well as to induce pain relief. Sixty-six patients who underwent
      shoulder arthroscopy for repair of small to medium rotator cuff tears were
      randomly divided into 2 groups with a block randomization procedure. Thirty-two
      patients underwent arthroscopic rotator cuff repair and application of pulsed
      electromagnetic fields postoperatively; 34 patients underwent rotator cuff repair
      and placebo treatment (placebo group). All patients had the same postoperative
      rehabilitation protocol. At 3 months from the index procedure, visual analog
      scale, range of motion, and University of California at Los Angeles and Constant
      scores were significantly better in the pulsed electromagnetic fields group than
      in the placebo group (P<.05). Three patients in the pulsed electromagnetic fields
      group and 7 patients in the placebo group had mild to moderate capsulitis (P=.2).
      Severe capsulitis occurred in 1 patient in the pulsed electromagnetic fields
      group and 2 patients in the placebo group (P=.6). At the last follow-up (minimum,
      2 years), clinical and functional outcomes were further improved in both groups,
      with no significant intergroup differences. Application of pulsed electromagnetic
      fields after rotator cuff repair is safe and reduces postoperative pain,
      analgesic use, and stiffness in the short term. At 2 years, no difference was
      seen in outcomes in patients who did or did not undergo treatment with pulsed
      electromagnetic fields.

PMID- 25760512
TI  - Preliminary trauma radiographs misrepresent pubic diastasis injuries.
AB  - The goal of this study was to evaluate the role of portable primary trauma survey
      radiographs in the evaluation and management of anteroposterior (AP) compression
      pelvic injuries. A retrospective analysis was conducted at a level I academic
      trauma center. Twenty-seven adults with AP compressive class pelvic ring injuries
      who received both portable pelvic radiographs and pelvic computed tomography (CT)
      imaging in an unbound pelvic state were included. Three orthopedic surgeons
      performed independent measurements of diastasis on portable pelvic radiographs
      and coronal pelvic CT reconstructions. Measurement techniques were standardized
      among observers and were repeated after 8 weeks to assess intraobserver
      reliability. Nonoperative vs operative treatments were correlated with the
      initial magnitude of pelvic injury on CT and portable radiographic images.
      Independent measurements of diastasis on both radiographs and CT scans showed
      excellent intraobserver reliability (average correlation coefficient, 0.986) and
      interobserver reliability (average correlation coefficient, 0.979). Compared with
      diastasis measurements on CT scans, portable pelvic radiographs overestimated
      diastasis by an average of 49%, or 12.6 mm (P<.0001; 95% confidence interval, 9.6
      15.6). Portable pelvic films were less precise than standard pelvic radiographs
      in measuring the size of femoral head controls (R(2)=0.919 vs 0.759; P=.004). In
      12 of the 27 patients evaluated, radiographic indications for operative pelvic
      fixation were met by portable radiographs but not CT scans, and 11 of these
      patients ultimately underwent operative fixation. Portable AP pelvic radiographs
      may distort and exaggerate pelvic bony injuries, especially those involving
      anterior pelvic structures. Surgeons should use caution when making management
      decisions based on preliminary portable pelvic radiographs.

PMID- 25760513
TI  - Modular hip implant fracture at the stem-sleeve interface.
AB  - The use of modular implants in femoral stem design has grown increasingly popular
      over the last decade because of the theoretical advantage of more flexibility and
      optimization of femoral anteversion, limb length, and femoral component offset.
      With the benefit of increased surgical flexibility, however, modularity also
      carries the theoretical risks of fretting at the modular surfaces, sequelae of
      wear debris, and possible failure and fracture of the stem at the modular
      junction. Indeed, there have been an increasing number of reports of modular
      implants failing due to fracture at modular junctions. The S-ROM prosthesis
      (DePuy Orthopaedics, Inc, Warsaw, Indiana), however, has a stellar clinical
      record and has been used with good results in both primary and revision total hip
      arthroplasty. Only a single case of S-ROM failure at the stem-sleeve interface
      has been reported in the orthopedic literature. The aim of this case report was
      to present a succinct history of proximal modularity in total hip arthroplasty
      and to describe the only known case of this type of catastrophic failure in an S
      ROM prosthesis with a metal-on-metal bearing. Despite a low level of serum metal
      ions on presentation, scanning electron microscopy showed findings consistent
      with corrosive processes and pseudotumor was seen at revision surgery.

PMID- 25760514
TI  - Bicondylar tibial plateau fracture after posterior cruciate ligament
      reconstruction.
AB  - The authors present a report of a bicondylar tibial plateau fracture in an
      adolescent athlete after posterior cruciate ligament (PCL) reconstruction. The
      procedure was performed via arthroscopic transtibial PCL reconstruction with
      quadrupled semi-tendinosus and gracilis autograft. The patient recovered
      uneventfully postoperatively and was able to participate in high-level sports
      activity, such as baseball and track, with no limitations, no subjective
      complaints, and no episodes of instability. He continued to be asymptomatic up to
      3.5 years postoperatively. Almost 4 years postoperatively, the patient reinjured
      the left knee during recreational noncontact football and was seen emergently.
      Plain radiographs, magnetic resonance image scan, and computed tomography scan at
      the time of injury showed a bicondylar tibial plateau fracture with intra
      articular involvement. Operative intervention was undertaken for open reduction
      and internal fixation of the bicondylar tibial plateau fracture. A plate was
      placed along the medial aspect of the tibia with locking and nonlocking screws,
      and the joint line was restored appropriately. The patient recovered uneventfully
      and at the most recent follow-up had full active and passive range of motion, had
      no subjective or objective evidence of instability, and had returned to full
      activity with no restrictions. The patient had no history of multiple fractures
      or any medical or pharmacologic history that predisposed him to decreased bone
      density. This case shows a unique possible complication after transtibial PCL
      reconstruction in an adolescent patient.

PMID- 25760515
TI  - Treatment of symptomatic intraosseous pneumatocyst using intraoperative
      navigation.
AB  - Intraosseous pneumatocysts are benign air-containing lesions that are most often
      found in the spine and pelvis and are nearly always treated nonoperatively.
      Although rarely clinically symptomatic, studies have shown pneumatocysts to be
      present in up to 10% of computed tomography (CT) scans of the pelvis and spine.
      Radiographic characteristics of these lesions include a localized collection of
      gas with a thin sclerotic rim, no bony destruction, no soft tissue masses, and no
      medullary abnormalities. Computed tomography is the diagnostic study of choice,
      with Hounsfield units ranging from -580 to -950, showing a gas-containing lesion.
      Few studies have described the management of symptomatic pneumatocysts, and all
      reported cases concern underwater divers, presumably because of greater pressure
      cycling and barotrauma encountered while underwater diving. The goal of this
      report is to describe the intraoperative CT-guided navigation and percutaneous
      injection of calcium sulfate-calcium phosphate composite bone graft substitute
      material for the treatment of a symptomatic pneumatocyst in the ilium of a Navy
      dive instructor. The patient reported a 1-year history of increasing buttock pain
      with increased depth of diving, consistently reproduced by diving past a depth of
      20 to 30 feet. To the authors' knowledge, this is the first description in the
      English literature of the operative treatment of an intraosseous pneumatocyst of
      the ilium. The use of intraoperative CT guidance permitted accurate percutaneous
      localization, decompression, and filling of the lesion with synthetic bone graft
      substitute, with complete early relief of symptoms. At 6-month follow up, the
      patient had reached diving depths of 170 feet without pain.

PMID- 25760516
TI  - Unprecedented trinuclear Ag(I) complex with 2,4,6-tris(2-pyrimidyl)-1,3,5
      triazine as an efficient catalyst for the aziridination of olefins.
AB  - An unprecedented trinuclear heteroleptic Ag(I) complex was isolated using a
      stable multidentate 2,4,6-tris(2-pyrimidyl)-1,3,5-triazine (TPymT) ligand. The
      obtained compound is an efficient catalyst for the direct aziridination of
      terminal olefins. 

PMID- 25760517
TI  - Change in knee contact force with simulated change in body weight.
AB  - The relationship between obesity, weight gain and progression of knee
      osteoarthritis is well supported, suggesting that excessive joint loading may be
      a mechanism responsible for cartilage deterioration. Examining the influence of
      weight gain on joint compressive forces is difficult, as both muscles and ground
      reaction forces can have a significant impact on the forces experienced during
      gait. While previous studies have examined the relationship between body weight
      and knee forces, these studies have used models that were not validated using
      experimental data. Therefore, the objective of this study was to evaluate the
      relationship between changes in body weight and changes in knee joint contact
      forces for an individual's gait pattern using musculoskeletal modeling that is
      validated against known internal compressive forces. Optimal weighting constants
      were determined for three subjects to generate valid predictions of knee contact
      forces (KCFs) using in vivo data collection with instrumented total knee
      arthroplasty. A total of five simulations per walking trial were generated for
      each subject, from 80% to 120% body weight in 10% increments, resulting in 50
      total simulations. The change in peak KCF with respect to body weight was found
      to be constant and subject-specific, predominantly determined by the peak force
      during the baseline condition at 100% body weight. This relationship may be
      further altered by any change in kinematics or body mass distribution that may
      occur as a result of a change in body weight or exercise program.

PMID- 25760518
TI  - Evaluation of a vaccination strategy by serosurveillance data: The case of
      varicella.
AB  - Serological studies have many important epidemiologic applications. They can be
      used to investigate acquisition of various infections in different populations,
      measure the induction of an immune response in the host, evaluate the persistence
      of antibody, identify appropriate target groups and the age for vaccination.
      Serological studies can also be used to determine the vaccine efficacy. Since
      1995 a varicella vaccine is available and it has been recommended in several
      countries (e.g. USA, Australia, Canada, Costa Rica, Ecuador, etc.). Nevertheless
      few varicella seroprevalence studies in countries that adopted an URV are
      available. It is related to the relatively recent introduction of the vaccination
      and to the lack of structured and collaborative surveillance systems based on
      serosurvey at national or regional level. Varicella seroprevalence data collected
      before the introduction of vaccination strategies allowed to establish the age of
      vaccination (e.g., indicated the opportunity to offer the vaccine to Italian
      susceptible adolescents). In the post-vaccination era, seroprevalence data
      demonstrated vaccine as immunogenic and excluded an increase of the age of
      infection linked to the vaccination strategy. New seroprevalence studies should
      be performed to answer to open questions, such as the long-term immunity and the
      change of the herpes zoster epidemiological pattern related to the vaccine. 

PMID- 25760519
TI  - Five Reasons to Consider Phytophthora infestans a Reemerging Pathogen.
AB  - Phytophthora infestans has been a named pathogen for well over 150 years and yet
      it continues to "emerge", with thousands of articles published each year on it
      and the late blight disease that it causes. This review explores five attributes
      of this oomycete pathogen that maintain this constant attention. First, the
      historical tragedy associated with this disease (Irish potato famine) causes many
      people to be fascinated with the pathogen. Current technology now enables
      investigators to answer some questions of historical significance. Second, the
      devastation caused by the pathogen continues to appear in surprising new
      locations or with surprising new intensity. Third, populations of P. infestans
      worldwide are in flux, with changes that have major implications to disease
      management. Fourth, the genomics revolution has enabled investigators to make
      tremendous progress in terms of understanding the molecular biology (especially
      the pathogenicity) of P. infestans. Fifth, there remain many compelling
      unanswered questions.

PMID- 25760520
TI  - Complete Nucleotide Sequence of Artichoke latent virus Shows it to be a Member of
      the Genus Macluravirus in the Family Potyviridae.
AB  - Complete genomic sequences of Artichoke latent virus (ArLV) have been obtained by
      classical or high-throughput sequencing for an ArLV isolate from Italy (ITBr05)
      and for two isolates from France (FR37 and FR50). The genome is 8,278 to 8,291
      nucleotides long and has a genomic organization comparable with that of Chinese
      yam necrotic mosaic virus (CYNMV), the only macluravirus fully sequenced to date.
      The cleavage sites of the viral polyprotein have been tentatively identified by
      comparison with CYNMV, confirming that macluraviruses are characterized by the
      absence of a P1 protein, a shorter and N-terminally truncated coat protein (CP).
      Sequence comparisons firmly place ArLV within the genus Macluravirus, and confirm
      previous results suggesting that Ranunculus latent virus (RALV), a previously
      described Macluravirus sp., is very closely related to ArLV. Serological
      relationships and comparisons of the CP gene and of the partial RaLV sequence
      available all indicate that RaLV should not be considered as a distinct species
      but as a strain of ArLV. The results obtained also suggest that the spectrum of
      currently used ArLV-specific molecular hybridization or polymerase chain reaction
      detection assays should be improved to cover all isolates and strains in the ArLV
      species. 

PMID- 25760521
TI  - Higher Potassium Concentration in Shoots Reduces Gray Mold in Sweet Basil.
AB  - Nutritional elements can affect plant susceptibility to plant pathogens,
      including Botrytis cinerea. We tested the effect of potassium (K) fertilization
      on gray mold in sweet basil grown in pots, containers, and soil. Increased K in
      the irrigation water and in the sweet basil tissue resulted in an exponential
      decrease in gray mold severity. Potassium supplied to plants by foliar
      application resulted in a significant decrease in gray mold in plants grown with
      a low rate of K fertigation. Lower K fertigation resulted in a significant
      increase in B. cinerea infection under semi-commercial conditions. Gray mold
      severity in harvested shoots was significantly negatively correlated with K
      concentration in the irrigation solution, revealing resistance to B. cinerea
      infection as a result of high K concentration in sweet basil tissue. Gray mold
      was reduced following K foliar application of the plants. In general, there was
      no synergy between the fertigation and foliar spray treatments. Proper K
      fertilization can replace some of the required chemical fungicide treatments and
      it may be integrated into gray mold management for improved disease suppression. 

PMID- 25760522
TI  - Genetic Diversity of the Indian Populations of 'Candidatus Liberibacter
      asiaticus' Based on the Tandem Repeat Variability in a Genomic Locus.
AB  - Citrus huanglongbing (HLB, citrus greening disease) is an extremely destructive
      disease affecting citrus and causes severe economic loss to the crop yield
      worldwide. The disease is caused by a phloem-limited, noncultured, gram-negative
      bacteria Candidatus Liberibacter spp., the widely present and most destructive
      species being 'Candidatus Liberibacter asiaticus'. Although the disease has been
      reported from almost all citrus growing regions of India, knowledge on the
      molecular variability of the pathogen 'Ca. L. asiaticus' populations from
      different geographical regions and cultivars is limited. In the present study,
      variability of the Indian 'Ca. L. asiaticus' based on the tandem repeats at the
      genomic locus CLIBASIA_01645 was characterized and categorized into four classes
      based on the tandem repeat number (TRN); Class I (TRN<=5), Class II (TRN>5<=10),
      Class III (TRN>10<=15), and Class IV (TRN>15). The study revealed that the Indian
      population of 'Ca. L. asiaticus' is more diverse than reported for Florida and
      Guangdong populations, which showed less diversity. While Florida and Guangdong
      populations were dominated by a TRN5 and TRN7 genotype, respectively, the Indian
      'Ca. L. asiaticus' populations with TRN copy numbers 9, 10, 11, 12, and 13 were
      widely distributed throughout the country. Additionally, TRN2 and TRN17 genotypes
      were also observed among the Indian 'Ca. L. asiaticus' populations. The
      predominant 'Ca. L. asiaticus' genotypes from the northeastern region of India
      were TRN6 and TRN7 (53.12%) and surprisingly similar to neighboring South China
      populations. Preliminary results showed absence of preference of citrus cultivars
      to any specific 'Ca. L. asiaticus' genotype.

PMID- 25760523
TI  - Effect of Maize Hybrid and Foliar Fungicides on Yield Under Low Foliar Disease
      Severity Conditions.
AB  - Foliar fungicide use in the U.S. Corn Belt increased in the last decade; however,
      questions persist pertaining to its value and sustainability. Multistate field
      trials were established from 2010 to 2012 in Illinois, Iowa, Ohio, and Wisconsin
      to examine how hybrid and foliar fungicide influenced disease intensity and
      yield. The experimental design was in a split-split plot with main plots
      consisting of hybrids varying in resistance to gray leaf spot (caused by
      Cercospora zeae-maydis) and northern corn leaf blight (caused by Setosphaera
      turcica), subplots corresponding to four application timings of the fungicide
      pyraclostrobin, and sub-subplots represented by inoculations with either C. zeae
      maydis, S. turcica, or both at two vegetative growth stages. Fungicide
      application (VT/R1) significantly reduced total disease severity relative to the
      control in five of eight site-years (P<0.05). Disease was reduced by
      approximately 30% at Wisconsin in 2011, 20% at Illinois in 2010, 29% at Iowa in
      2010, and 32 and 30% at Ohio in 2010 and 2012, respectively. These disease
      severities ranged from 0.2 to 0.3% in Wisconsin in 2011 to 16.7 to 22.1% in
      Illinois in 2010. The untreated control had significantly lower yield (P<0.05)
      than the fungicide-treated in three site-years. Fungicide application increased
      the yield by approximately 6% at Ohio in 2010, 5% at Wisconsin in 2010 and 6% in
      2011. Yield differences ranged from 8,403 to 8,890 kg/ha in Wisconsin 2011 to
      11,362 to 11,919 kg/ha in Wisconsin 2010. Results suggest susceptibility to
      disease and prevailing environment are important drivers of observed differences.
      Yield increases as a result of the physiological benefits of plant health
      benefits under low disease were not consistent.

PMID- 25760525
TI  - Antibacterial Biphenanthrenes from the Fibrous Roots of Bletilla striata.
AB  - Four new 9',10'-dihydro-biphenanthrenes, including an unprecedented 1,2'-linked
      biphenanthrene, 4,7,3',5'-tetramethoxy-9',10'-dihydro(1,2'-biphenanthrene)-2,7'
      diol (1), a new 1,3'-linked biphenanthrene, 4,7,7'-trimethoxy-9',10'-dihydro(1,3'
      biphenanthrene)-2,2',5'-triol (2), and two new 1,1'-linked biphenanthrenes,
      4,7,4'-trimethoxy-9',10'-dihydro(1,1'-biphenanthrene)-2,2',7'-triol (3) and
      4,7,3',5'-tetramethoxy-9',10'-dihydro(1,1'-biphenanthrene)-2,2',7'-triol (4), as
      well as two known biphenanthrenes (5, 6), were isolated from a 95% ethanol
      extract of the fibrous roots of Bletilla striata. Their structures were
      determined by spectroscopic and spectrometric methods. Atropisomerism of these
      compounds was considered based on their chiral optical properties and potential
      energy surface scans at the ab initio HF/3-21G level, which revealed their
      racemic mixture form. Compounds 2-6 showed potent antibacterial activities
      against six Gram-positive bacterial strains. 

PMID- 25760526
TI  - Significance of non-cytochrome P450 (non-P450) enzymes in basic science, clinical
      field and drug development.

PMID- 25760527
TI  - Structural plasticity in the human cytosolic sulfotransferase dimer and its role
      in substrate selectivity and catalysis.
AB  - The cytosolic sulfotransferases (SULTs) are dimeric enzymes that help maintain
      homeostasis through the modulation of hormone and drug activity by catalyzing
      their transformation into hydrophilic sulfate esters and increasing their
      excretion. Each of the thirteen active human SULT isoforms displays a unique
      substrate specificity pattern that underlies its individual role in our bodies.
      These specificities have proven to be complex, in some cases masking the
      biological role of specific isoforms. The first part of this review offers a
      short summary of historical underpinnings of human SULTs, primarily centered on
      the characterization of each isoform's kinetic and structural properties. Recent
      structural investigations have revealed each SULT has an active site "lid" that
      undergoes restructuring once the cofactor/sulfonate donor, 3'-phosphoadenosine-5'
      phosphosulfate (PAPS), binds to the enzyme. This structural rearrangement can
      alter substrate-binding profiles, therefore complicating enzyme/substrate
      interactions and making substrate/cosubstrate concentrations and binding order
      important considerations in enzyme functionality. Molecular dynamic simulations
      have recently been employed to describe this restructuring in an attempt to offer
      insight to its effects on substrate selectivity. In addition to reviewing new
      data on SULT molecular dynamics, we will discuss the contribution of PAPS
      concentrations and SULT dimerization in the regulation of SULT activity within
      the human body. 

PMID- 25760528
TI  - Prediction of hepatic and intestinal glucuronidation using in vitro-in vivo
      extrapolation.
AB  - The accurate prediction of hepatic (Fh) and intestinal availability (Fg) is vital
      for determining human pharmacokinetics. To predict these PK parameters for
      cytochrome P450 (P450) metabolism, in vitro-in vivo extrapolation (IVIVE) using
      hepatic microsomes, hepatocytes, and intestinal microsomes has been actively
      investigated. However, IVIVE has not been sufficiently evaluated for non-P450
      enzymes. UDP-glucuronosyltransferase (UGT) is a non-P450 enzyme that catalyzes
      glucuronidation, a major pathway for drugs possessing carboxylic acid, hydroxyl,
      and amine moieties. In drug metabolism, UGT is the most important enzyme after
      P450, and prediction of Fh for UGT substrates has mainly been attempted using
      hepatic models based on the clearance concepts. While various approaches for
      achieving improved prediction of clearance have been investigated--such as the
      addition of bovine serum albumin to microsomal incubation mixtures--optimized in
      vitro methods that utilize both hepatic microsomes and hepatocytes for more
      accurate prediction are still required. Although application of the simplified
      intestinal availability (SIA) model is effective in predicting the Fg of UGT
      substrates, this model is limited to compounds with high oral absorption. In this
      review, we discuss the current state, issues, and future directions of predicting
      Fh and Fg for glucuronidation.

PMID- 25760529
TI  - A comprehensive review of UDP-glucuronosyltransferase and esterases for drug
      development.
AB  - UDP-glucuronosyltransferase (UGT) and esterases are recognized as the most
      important non-P450 enzymes because of their high contribution to drug metabolism.
      UGTs catalyze the transfer of glucuronic acid to hydroxyl, carboxyl, or amine
      groups of compounds, whereas esterases hydrolyze compounds that contain ester,
      amide, and thioester bonds. These enzymes, in most cases, convert hydrophobic
      compounds to water-soluble metabolites to facilitate the elimination of compounds
      from the body. Information about these enzymes is steadily increasing, although
      our knowledge is still behind our understanding of P450. This review gives an
      overview of recent findings in UGT and esterases studies focusing on tissue
      distribution, gene regulation, substrate and inhibitor specificity, and species
      differences. In particular, the absolute protein content of UGT isoforms and
      esterases in human tissues could be available. In the field of esterases, it is
      becoming clear that enzymes other than carboxylesterase are involved in drug
      hydrolysis. In addition, there is an interesting interplay between UGTs and
      esterases in the formation and hydrolytic deglucuronidation of acyl-glucuronide,
      which is considered to be a reactive metabolite. With the growing awareness of
      the importance of non-P450 enzymes in drug development, issues that should be
      resolved are discussed. 

PMID- 25760530
TI  - Significance of aldehyde oxidase during drug development: Effects on drug
      metabolism, pharmacokinetics, toxicity, and efficacy.
AB  - Aldehyde oxidase contributes to drug metabolism and pharmacokinetics (PK), and a
      few clinical studies were discontinued because of aldehyde oxidase metabolism.
      Its AOX1, AOX3, AOX3L1, and AOX4 isoforms are expressed in mammals, and species
      differences in expression profiles reflect differences in drug metabolism and PK
      between animals and humans. Individual differences in aldehyde oxidase activity
      also influence drug metabolism in humans. Moreover, the reduced solubility of the
      aldehyde oxidase metabolites may induce drug toxicity. Because various drugs
      inhibit aldehyde oxidase, assessments of ensuing drug-drug interactions (DDI) are
      critical for drug optimization. Although drug metabolism, PK, safety, and DDI are
      important, drugs such as famciclovir and O6-benzylguanine that affect aldehyde
      oxidase activity in humans have been reported. Recently, various in vitro
      approaches have been developed to predict PK in humans. However, in vitro studies
      on aldehyde oxidase may be hampered because of its instability. In contrast, in
      vivo studies on chimeric mice with humanized livers have also been focused on to
      predict aldehyde oxidase-mediated metabolism. Additionally, the ratios of N1
      methylnicotinamide to metabolites in urinary excretions may represent useful
      biomarkers of aldehyde oxidase activity in humans. Thus, assessing the
      contributions of aldehyde oxidase to drug metabolism in humans is necessary.

PMID- 25760531
TI  - Benzydamine N-oxygenation as an index for flavin-containing monooxygenase
      activity and benzydamine N-demethylation by cytochrome P450 enzymes in liver
      microsomes from rats, dogs, monkeys, and humans.
AB  - Benzydamine is an anti-inflammatory drug that undergoes flavin-containing
      monooxygenase (FMO)-dependent metabolism to benzydamine N-oxide; however,
      benzydamine N-demethylation is also catalyzed by liver microsomes. In this study,
      benzydamine N-oxygenation and N-demethylation mediated by liver microsomes from
      rats, dogs, monkeys, and humans were characterized comprehensively. Values of the
      maximum velocity/Michaelis constant ratio for benzydamine N-oxygenation by liver
      microsomes from dogs and rats were higher than those from monkeys and humans,
      despite roughly similar rates of N-demethylation in the four species. Benzydamine
      N-oxygenation by liver microsomes was extensively suppressed by preheating liver
      microsomes at 45  degrees C for 5 min or at 37  degrees C for 5-10 min without
      NADPH, and benzydamine N-demethylation was strongly inhibited by 1
      aminbobenztriazole. Liver microsomal benzydamine N-oxygenation was inhibited by
      dimethyl sulfoxide and methimazole, whereas N-demethylation was inhibited by
      quinidine. High benzydamine N-oxygenation activities of recombinant human FMO1
      and FMO3 and human kidney microsomes were observed at pH 8.4, whereas N
      demethylation by cytochrome P450 2D6 was faster at pH 7.4. These results suggest
      that benzydamine N-oxygenation and N-demethylation are mediated by FMO1/3 and
      P450s, respectively, and that the contribution of FMO to metabolic eliminations
      of new drug candidates might be underestimated under certain experimental
      conditions suitable for P450 enzymes.

PMID- 25760532
TI  - Potential for drug interactions mediated by polymorphic flavin-containing
      monooxygenase 3 in human livers.
AB  - Human flavin-containing monooxygenase 3 (FMO3) in the liver catalyzes a variety
      of oxygenations of nitrogen- and sulfur-containing medicines and xenobiotic
      substances. Because of growing interest in drug interactions mediated by
      polymorphic FMO3, benzydamine N-oxygenation by human FMO3 was investigated as a
      model reaction. Among the 41 compounds tested, trimethylamine, methimazole,
      itopride, and tozasertib (50 MUM) suppressed benzydamine N-oxygenation at a
      substrate concentration of 50 MUM by approximately 50% after co-incubation.
      Suppression of N-oxygenation of benzydamine, trimethylamine, itopride, and
      tozasertib and S-oxygenation of methimazole and sulindac sulfide after co
      incubation with the other five of these six substrates was compared using FMO3
      proteins recombinantly expressed in bacterial membranes. Apparent competitive
      inhibition by methimazole (0-50 MUM) of sulindac sulfide S-oxygenation was
      observed with FMO3 proteins. Sulindac sulfide S-oxygenation activity of Arg205Cys
      variant FMO3 protein was likely to be suppressed more by methimazole than wild
      type or Val257Met variant FMO3 protein was. These results suggest that genetic
      polymorphism in the human FMO3 gene may lead to changes of drug interactions for
      N- or S-oxygenations of xenobiotics and endogenous substances and that a probe
      battery system of benzydamine N-oxygenation and sulindac sulfide S-oxygenation
      activities is recommended to clarify the drug interactions mediated by FMO3.

PMID- 25760533
TI  - The metabolism of lysophosphatidic acids by allelic variants of human soluble
      epoxide hydrolase.
AB  - Lysophosphatidic acids (LPAs) are phospholipids which have many physiological and
      pathophysiological functions. The human soluble epoxide hydrolase (sEH) plays a
      role in the metabolism of xenobiotics through its metabolism of aromatic
      hydrocarbon epoxides such as styrene oxide. sEH also has a phosphatase activity,
      and metabolizes LPAs. In this study, we investigated a purified wild-type (WT)
      and six allelic variants of sEH to evaluate differences in their activities
      toward LPAs. We found that the R103C and R287Q showed significantly lower
      activity than the WT sEH. We also found that the R103C and R287Q had
      significantly lower activity even when applied to only the N-terminal or C
      terminal domain. The kinetic study determined that the R103C and R287Q had a
      lower Vmax/Km ratio toward stearoyl-LPA than the other variants. In a previous
      study, we found that WT sEH suppressed vascular endothelial growth factor (VEGF)
      mRNA in Hep3B cells; in the present experiments, all sEH variants except V442A
      suppressed VEGF mRNA levels in Hep3B cells. These results suggest that the R103C
      and R287Q have lower phosphatase activity, but that all the allelic variants have
      similar effects on VEGF suppression. 

PMID- 25760534
TI  - UDP-glucuronosyltransferase (UGT) 1A1 mainly contributes to the glucuronidation
      of trovafloxacin.
AB  - Identification of drug-metabolizing enzyme(s) responsible for the metabolism of
      drugs is an important step to understand not only interindividual variability in
      pharmacokinetics but also molecular mechanisms of metabolite-related toxicity.
      While it was reported that the major metabolic pathway of trovafloxacin, which is
      an antibiotic, was glucuronidation, the UDP-glucuronosyltransferase (UGT)
      isoform(s) responsible for the trovafloxacin glucuronidation has not been
      identified yet. In the present study, among the functional human UGT members,
      UGT1A1, UGT1A3, and UGT1A9 exhibited higher trovafloxacin acyl-glucuronidation
      activities. While other UGT members such as UGT1A8, UGT2B7, and UGT2B15 showed
      glucuronidation activity toward trovafloxacin, the metabolic velocity was
      extremely low. In human liver microsomes, trovafloxacin acyl-glucuronidation
      followed the Hill equation with S50 value of 95 MUM, Vmax value of 243 pmol/min
      per mg, and a Hill coefficient of 2.0, while the UGT1A1-expressing system
      displayed Michaelis-Menten kinetics with a substrate inhibition, with Km value of
      759 MUM and Vmax value of 1160 pmol/min per mg. In human liver microsomes
      prepared from poor metabolizers (UGT1A1*28/*28), significantly reduced
      trovafloxacin acyl-glucuronide formation activity was observed, indicating that
      UGT1A1 mainly, while other UGT members such as UGT1A3 and UGT1A9 partially,
      contributes to the glucuronidation of trovafloxacin.

PMID- 25760535
TI  - In vitro glucuronidation of the primary metabolite of 10-chloromethyl-11-demethyl
      12-oxo-calanolide A by human liver microsomes and its interactions with UDP
      glucuronosyltransferase substrates.
AB  - F18 (10-chloromethyl-11-demethyl-12-oxo-calanolide), an analog of (+)-Calanolide
      A, is a novel small-molecule nonnucleoside reverse transcriptase inhibitor for
      the therapy of human immunodeficiency virus (HIV) infection. M3, the most
      abundant primary metabolite of F18 in human liver microsomes (HLMs) and rat liver
      microsomes (RLMs), is mainly excreted in bile as a glucuronide conjugate in rats
      after oral administration. The aim of this study was to identify the UDP
      glucuronosyltransferase (UGT) isoforms involved in the glucuronidation of M3 by
      HLMs and recombinant human UGTs and investigate the metabolic interactions of M3
      with the substrates of UGTs in HLMs. As a result, UGT1A1 was the major isozyme
      responsible for the glucuronidation of M3, followed by UGT1A4, UGT1A9 and UGT2B7.
      M3 exhibited significant inhibition against UGT1A9 and UGT2B7 in both HLMs and
      recombinant human UGTs. In addition, M3 inhibited UGT1A9 catalyzed mycophenolic
      acid (MPA) glucuronidation with Ki of 0.39 MUM, and M3 also inhibited the
      glucuronidation of 3'-azido-3'-deoxythymidine (AZT) by a "mixed-type" mechanism
      with Ki of 16.8 MUM. The results suggest that UGT1A1 provides the major
      contribution to M3 glucuronidation in vitro and M3 has the potential to interact
      with xenobiotics and endogenous chemicals that are UGT1A9 and UGT 2B7 substrates.

PMID- 25760536
TI  - Exogenous dopamine induces dehydroepiandrosterone sulfotransferase (rSULT2A1) in
      rat liver and changes the pharmacokinetic profile of moxifloxacin in rats.
AB  - Dehydroepiandrosterone sulfotransferase (SULT2A1) plays an important role in the
      detoxification of hydroxyl-containing xenobitotics and in the regulation of the
      biological activities of hydroxysteroids. Although dopamine (DA) is a vital
      neurotransmitter, DA also has some special functions in outer peripheral system
      and takes effect by binding with dopamine receptors including five subtypes (D1
      D5). The objective of this study was to investigate the effect of exogenous DA on
      both the regulation of rSULT2A1 (rat SULT2A1) and the pharmacokinetics of
      moxifloxacin which is a specific substrate of rSULT2A1. After different doses of
      DA (0, 2, 10 and 100 mg/kg/d) were administrated to both male and female rats for
      7 days, the activity, protein level and mRNA expression of rSULT2A1 increased
      significantly. Moreover, both Cmax and AUC of moxifloxacin decreased and AUC of
      moxifloxacin sulfate conjugate metabolite increased significantly when
      moxifloxacin was administered to rats with DA pretreatment. Additionally, D1
      expression in liver and cAMP concentration also increased after the treatment
      with DA. Overall these results suggest that exogenous DA may induce rSULT2A1 in
      rat liver and may further change the pharmacokinetic characteristics of some
      substrates of SULT2A1, and the activation of D1-like receptor is probably
      involved in rSULT2A1 induction by DA.

PMID- 25760537
TI  - Effects of cytokines on CYP3A4 expression and reversal of the effects by anti
      cytokine agents in the three-dimensionally cultured human hepatoma cell line FLC
      4.
AB  - The expression of hepatic cytochrome P450 (CYP) enzymes is altered under
      pathological conditions with increased levels of cytokines. In this study, we
      analyzed the effects of cytokines (interleukin [IL]-1beta, IL-6 and tumor
      necrosis factor alpha) on the expression of CYP3A4 using newly introduced three
      dimensionally cultured human hepatocarcinoma FLC-4 cells. The mRNA level of
      CYP3A4 was significantly decreased by IL-1beta, IL-6 and tumor necrosis factor
      alpha. Formation of alpha-hydroxytriazolam catalyzed by CYP3A was decreased by IL
      1beta and IL-6. Pre-treatment with IL-6 enhanced the cytotoxic effects of
      gefitinib and paclitaxel. In addition, tocilizumab and IL-1 receptor antagonist
      restored the decreased expression of CYP3A4 mRNA by IL-6 and IL-1beta,
      respectively. These results obtained by using three-dimensionally cultured FLC-4
      cells are consistent with results obtained by using primary human hepatocytes and
      results of clinical studies. Therefore, three-dimensionally cultured FLC-4 cell
      system may be a promising cellular tool to assess the effects of cytokines on
      CYP3A4 expression. 

PMID- 25760538
TI  - Analysis of TGF-beta1- and drug-induced epithelial-mesenchymal transition in
      cultured alveolar epithelial cell line RLE/Abca3.
AB  - In this study, we examined the induction of epithelial-mesenchymal transition
      (EMT) by transforming growth factor (TGF)-beta1 and drugs in genetically
      engineered type II alveolar epithelial cell line RLE/Abca3. Treatment of
      RLE/Abca3 cells with TGF-beta1 induced marked changes in cell morphology from
      epithelial-like to elongated fibroblast-like morphology. With these morphological
      changes, mRNA expression of epithelial markers such as cytokeratin 19 (CK19)
      decreased, while that of mesenchymal markers such as alpha-smooth muscle actin
      (alpha-SMA) increased. TGF-beta1 treatment also decreased the mRNA expression of
      Abca3, a type II cell marker, and formation of lamellar body structures.
      Interestingly, the effect of TGF-beta1 on Abca3 mRNA expression was observed in
      RLE/Abca3 cells, but not in wild-type RLE-6TN, A549, and H441 cells. Treatment of
      RLE/Abca3 cells with bleomycin (BLM) and methotrexate (MTX) induced similar
      morphological and mRNA expression changes. In addition, the increase in alpha-SMA
      and the decrease in Abca3 mRNA expression by these drugs were observed only in
      RLE/Abca3 cells. These findings suggest that, like TGF-beta1, BLM and MTX induce
      EMT in RLE/Abca3 cells, and RLE/Abca3 cells would be a good model to study drug
      induced EMT. The effect of pirfenidone, an antifibrotic and anti-inflammatory
      drug, on EMT induced by TGF-beta1 was also discussed. 

PMID- 25760539
TI  - Functional characterization of 10 CYP4A11 allelic variants to evaluate the effect
      of genotype on arachidonic acid omega-hydroxylation.
AB  - Genetic variations in cytochrome P450 4A11 (CYP4A11) contributes to inter
      individual variability in the metabolism of fatty acids such as arachidonic acid.
      CYP4A11 metabolizes arachidonic acid to 20-hydroxyeicosatetraenoic acid (20
      HETE), which is important for the regulation of blood pressure. Polymorphisms in
      CYP4A11 are associated with susceptibility to hypertension. In this study, we
      evaluated the in vitro omega-hydroxylation of arachidonic acid by 10 CYP4A11
      allelic variants, which cause amino acid substitutions in the encoded proteins.
      CYP4A11 variants were heterologously expressed in COS-7 cells and the kinetic
      parameters of arachidonic acid omega-hydroxylation were estimated. Among 10
      CYP4A11 variants, 5 (CYP4A11-v1, CYP4A11-v2, CYP4A11-v3, CYP4A11-v4, and CYP4A11
      v7) showed no or markedly lower activity compared to wild-type CYP4A11. This
      functional analysis of CYP4A11 variants could provide useful information for the
      effective prevention and treatment of hypertension.

PMID- 25760540
TI  - Effect of CAR polymorphism on the pharmacokinetics of artemisinin in healthy
      Chinese subjects.
AB  - Repeated pretreatment with the antimalarial drug artemisinin (QHS) could lead to
      reduced exposure to the parent drug, which is mainly mediated by auto-induction
      of CYP2B6 activity. CYP2B6 is most sensitive to the inductive effect of
      constitutive androstane receptor (CAR), which can be activated by QHS. CYP2B6
      polymorphism has no influence on pharmacokinetics of QHS derivatives. This study
      aimed to investigate the effect of CAR (C540T) polymorphism on the auto-induction
      metabolism-mediated pharmacokinetics of QHS. Healthy Chinese subjects (six in
      each group with the genotypes of CAR 540C/C, 540C/T and 540T/T; all carrying the
      CYP2B6*1*1 genotype) received a recommended two-day oral doses of QHS-piperaquine
      (PQ) to assess the pharmacokinetics of QHS and its metabolite deoxyartemisinin
      (DQHS). The exposures to QHS and DQHS were significantly lower (p < 0.05) in
      subjects homozygous for the CAR 540T/T genotype than those with the 540C/C
      genotype after the repeated dose. QHS did not show different induction clearance
      in subjects homozygous for the 540C/C genotype (1.3-fold), compared with those
      carrying the heterozygous 540C/T (2.1-fold) or homozygous 540T/T (1.7-fold)
      genotype. In conclusion, the CAR (C540T) genotype contributed to the
      interindividual variability of QHS pharmacokinetics, and the dose regimen for QHS
      deserves further evaluation especially in specific populations.

PMID- 25760541
TI  - Novel single nucleotide polymorphisms of the dihydropyrimidinase gene (DPYS) in
      Japanese individuals.
AB  - Genetic polymorphisms of the dihydropyrimidinase gene (DPYS) may be associated
      with the development of severe toxicity to 5-fluorouracil, a drug used to treat
      solid tumors. In this study, we analyzed the nine coding exons and exon-intron
      junctions of DPYS in 183 Japanese individuals. We detected two novel single
      nucleotide polymorphisms (SNPs)-285C > T (Thr95Thr) and 349T > C (Trp117Arg)-in
      exon 2. The nonsynonymous SNP 349T > C was analyzed in 208 Japanese individuals.
      Although the allele frequency of the SNP in the Japanese population was found to
      be extremely low (0.13%), the enzymatic activity of the variant protein might be
      reduced compared with that of the wild-type protein.

PMID- 25760542
TI  - Genetic polymorphism of cynomolgus and rhesus macaque CYP2C9.
AB  - Cynomolgus and rhesus macaques are non-human primate species widely used in drug
      metabolism studies. Cynomolgus CYP2C9 (formerly known as CYP2C43) is
      predominantly expressed in liver and encodes a drug-metabolizing enzyme that
      metabolizes human CYP2C substrates such as S-mephenytoin and progesterone. In
      addition, cynomolgus CYP2C9 also metabolizes caffeine, resulting in the formation
      of the metabolite that is not generated efficiently in humans. Genetic variants
      of human CYP2C genes account for the inter-individual variability in drug
      metabolism: however, CYP2C9 variants have not been found in macaques. To see if
      CYP2C9 is polymorphic in macaques, in this study, CYP2C9 was re-sequenced in 78
      cynomolgus and 36 rhesus macaques. A total of 27 non-synonymous variants were
      found, among which 4 were located in substrate recognition sites, the domain
      important for protein function. Thirteen and seven variants were unique to
      cynomolgus and rhesus macaques, respectively. This study revealed the polymorphic
      nature of cynomolgus and rhesus CYP2C9, similar to human CYP2C genes, by
      identification of numerous genetic variants including non-synonymous variants. 

PMID- 25760543
TI  - Direct synthesis of N-H carbazoles via iridium(III)-catalyzed intramolecular C-H
      amination.
AB  - The iridium-catalyzed dehydrogenative cyclization of 2-aminobiphenyls proceeds
      smoothly in the presence of a copper cocatalyst under air as a terminal oxidant
      through intramolecular direct C-H amination to produce N-H carbazoles. A similar
      iridium/copper system can also catalyze the unprecedented dimerization reaction
      of 2-aminobiphenyl involving 2-fold C-H/N-H couplings. 

PMID- 25760544
TI  - Nazarov cyclization of divinyl and arylvinyl epoxides: application in the
      synthesis of resveratrol-based natural products.
AB  - New variation in the Nazarov cyclization has been developed by preparing divinyl
      and arylvinyl epoxides as pentadienyl cation precursors for the first time.
      Highly substituted cyclopentadienes, hydrindienes, and indenes were synthesized
      to demonstrate the compatibility of this reaction with substrates bearing a
      variety of substitutions and having different types of epoxides. Application of
      this method in the synthesis of resveratrol-based natural products was also
      demonstrated. 

PMID- 25760545
TI  - Adding 5 h delayed xenon to delayed hypothermia treatment improves long-term
      function in neonatal rats surviving to adulthood.
AB  - BACKGROUND: We previously reported that combining immediate hypothermia with
      immediate or 2 h delayed inhalation of an inert gas, xenon, gave additive
      neuroprotection in rats after a hypoxic-ischemic insult, compared to hypothermia
      alone. Defining the therapeutic time window for this new combined intervention is
      crucial in clinical practice when immediate treatment is not always feasible. The
      aim of this study is to investigate whether combined hypothermia and xenon still
      provide neuroprotection in rats after a 5 h delay for both hypothermia and xenon.
      METHODS: Seven-day-old Wistar rat pups underwent a unilateral hypoxic-ischemic
      insult. Pups received 5 h of treatment starting 5 h after the insult randomized
      between normothermia, hypothermia, or hypothermia with 50% xenon. Surviving pups
      were tested for fine motor function through weeks 8-10 before being euthanized at
      week 11. Their hemispheric and hippocampal areas were assessed. RESULTS: Both
      delayed hypothermia-xenon and hypothermia-only treated groups had significantly
      less brain tissue loss than those which underwent normothermia. The functional
      performance after 1 wk and adulthood was significantly better after hypothermia
      xenon treatment as compared to the hypothermia-only or normothermia groups.
      CONCLUSION: Adding 50% xenon to 5 h delayed hypothermia significantly improved
      functional outcome as compared to delayed hypothermia alone despite similar
      reductions in brain area.

PMID- 25760546
TI  - Spatial and temporal patterns in preterm birth in the United States.
AB  - BACKGROUND: Despite years of research, the etiologies of preterm birth remain
      unclear. In order to help generate new research hypotheses, this study explored
      spatial and temporal patterns of preterm birth in a large, total-population
      dataset. METHODS: Data on 145 million US births in 3,000 counties from the
      Natality Files of the National Center for Health Statistics for 1971-2011 were
      examined. State trends in early (<34 wk) and late (34-36 wk) preterm birth rates
      were compared. K-means cluster analyses were conducted to identify gestational
      age distribution patterns for all US counties over time. RESULTS: A weak
      association was observed between state trends in <34 wk birth rates and the
      initial absolute <34 wk birth rate. Significant associations were observed
      between trends in <34 wk and 34-36 wk birth rates and between white and African
      American <34 wk births. Periodicity was observed in county-level trends in <34 wk
      birth rates. Cluster analyses identified periods of significant heterogeneity and
      homogeneity in gestational age distributional trends for US counties. CONCLUSION:
      The observed geographic and temporal patterns suggest periodicity and complex,
      shared influences among preterm birth rates in the United States. These patterns
      could provide insight into promising hypotheses for further research.

PMID- 25760547
TI  - Lead exposure in preterm infants receiving red blood cell transfusions.
AB  - BACKGROUND: Preterm infants may inadvertently be exposed to lead from the packed
      red blood cell (pRBC) transfusions with almost no or very limited data available.
      The aim of the study was to quantify this exposure in preterm infants <=30 wk
      gestational age (GA). METHODS: Prospective cohort study, infants <=30 wk GA were
      eligible, infants < 23 wk GA and known chromosomal diseases were excluded. Blood
      lead levels (BLLs) were obtained at birth, before and after each transfusion, and
      at discharge. BLLs were also obtained from the donor pRBC aliquot transfused. A
      linear mixed model analysis was done. RESULTS: Of 75 infants, 34 received a total
      of 126 pRBC transfusions. Each infant had an average of 3.7 transfusions. 92% of
      lead levels in the transfused aliquot were <= 5 mcg/dl, 6.8% were between 6-8
      mcg/dl and 1 had a level of 56 mcg/dl. Average total lead load was 1.3 mcg/dl.
      For each 1 mcg/dl increase in transfused pRBC lead level, infant's post
      transfusion BLL increased by 0.20 mcg/dl (95% CI: 0.07 mcg/dl, 0.33 mcg/dl; P =
      0.002), adjusting for GA and birth weight. There was no significant increase in
      discharge BLLs, which were similar for both transfused and nontransfused infants.
      CONCLUSION: Post-transfusion infant BLLs correlate significantly with the
      transfused pRBCs lead level.

PMID- 25760548
TI  - Adiponectin oligomers are similarly distributed in adequate-for-gestational-age
      obese children irrespective of feeding in their first year.
AB  - BACKGROUND: Nutrition and growth in early postnatal life have a role in future
      diseases. Our aim was to investigate adiponectin oligomers in adequate-for
      gestational-age obese children with respect to type and duration of feeding in
      the first year of life. METHODS: Adiponectin oligomers and cardiometabolic risk
      factors were measured in 113 adequate-for-gestational-age obese children, divided
      into group A (prolonged breast feeding, >6 mo), group B (short breast feeding, 1
      6 mo), and group C (formula feeding from birth). RESULTS: All the parameters were
      similar among the groups. Adiponectin oligomers did not correlate with
      gestational age, months of breast feeding, and time of weaning. Total and high
      molecular weight adiponectin were differently distributed across gender and
      pubertal stages (P < 0.02), being lower in males from the start of puberty.
      Prepregnancy BMI and at the end of the pregnancy were negatively associated (P <
      0.04) with total and medium-molecular weight adiponectin in female and male
      offspring, respectively. CONCLUSIONS: Adiponectin oligomers and metabolic
      characteristics are similarly distributed in adequate-for-gestational-age obese
      children, irrespective of the type and duration of the feeding in the first year
      of life. Gender and mother's BMI in pregnancy are contributors to adiponectin
      regulation. Further studies will explain whether breastfeeding protects against
      metabolic impairment later in life.

PMID- 25760549
TI  - Activin A contributes to the development of hyperoxia-induced lung injury in
      neonatal mice.
AB  - BACKGROUND: Bronchopulmonary dysplasia (BPD) is one of the leading causes of
      morbidity and mortality in babies born prematurely, yet there is no curative
      treatment. In recent years, a number of inhibitors against TGFbeta signaling have
      been tested for their potential to prevent neonatal injury associated with
      hyperoxia, which is a contributing factor of BPD. In this study, we assessed the
      contribution of activin A-a member of the TGFbeta superfamily-to the development
      of hyperoxia-induced lung injury in neonatal mice. METHODS: We placed newborn
      C57Bl6 mouse pups in continuous hyperoxia (85% O2) to mimic many aspects of BPD
      including alveolar simplification and pulmonary inflammation. The pups were
      administered activin A receptor type IIB-Fc antagonist (ActRIIB-Fc) at 5 mg/kg or
      follistatin at 0.1 mg/kg on postnatal days 4, 7, 10, and 13. RESULTS: Treatment
      with ActRIIB-Fc and follistatin protected against hyperoxia-induced growth
      retardation. ActRIIB-Fc also reduced pulmonary leukocyte infiltration, normalized
      tissue: airspace ratio and increased septal crest density. These findings were
      associated with reduced phosphorylation of Smad3 and decreased matrix
      metalloproteinase (MMP)-9 activity. CONCLUSION: This study suggests that activin
      A signaling may contribute to the pathology of bronchopulmonary dysplasia.

PMID- 25760550
TI  - Factors influencing gastrointestinal tract and microbiota immune interaction in
      preterm infants.
AB  - The role of microbial colonization is indispensable for keeping a balanced immune
      response in life. However, the events that regulate the establishment of the
      microbiota, their timing, and the way in which they interact with the host are
      not yet fully understood. Factors such as gestational age, mode of delivery,
      environment, hygienic measures, and diet influence the establishment of
      microbiota in the perinatal period. Environmental microbes constitute the most
      important group of exogenous stimuli in this critical time frame. However, the
      settlement of a stable gut microbiota in preterm infants is delayed compared to
      term infants. Preterm infants have an immature gastrointestinal tract and immune
      system which predisposes to infectious morbidity. Neonatal microbial dynamics and
      alterations in early gut microbiota may precede and/or predispose to diseases
      such as necrotizing enterocolitis (NEC), late-onset sepsis or others. During this
      critical period, nutrition is the principal contributor for immunological and
      metabolic development, and microbiological programming. Breast milk is a known
      source of molecules that act synergistically to protect the gut barrier and
      enhance the maturation of the gut-related immune response. Host-microbe
      interactions in preterm infants and the protective role of diet focused on breast
      milk impact are beginning to be unveiled. 

PMID- 25760551
TI  - The association between linoleic acid levels in colostrum and child cognition at
      2 and 3 y in the EDEN cohort.
AB  - BACKGROUND: Breastfeeding has been associated with improved cognitive
      development. This may be explained by polyunsaturated fatty acid (PUFA) content
      of breast milk, especially long-chain (LC) PUFA that are needed for postnatal
      brain growth. METHODS: Using data from the French EDEN cohort, we aimed to study
      whether the PUFA content of colostrum may explain observed associations between
      breastfeeding duration and cognitive scores at 2 and 3 y. A total of 709
      breastfed children with available data on PUFA composition of milk were assessed
      using parent-reported questionnaires for motor and language at 2 y of age, or
      global cognition at 3 y. Multiple linear regressions were used to examine
      associations between PUFA levels and child cognitive scores, after controlling
      for many confounders. RESULTS: We found no association between LCPUFA levels in
      colostrum and child development. However, levels of linoleic acid (LA) were
      negatively associated with motor and cognitive scores, independently of
      breastfeeding duration. Children breastfed with the highest levels of LA tended
      to score closer to the never breastfed children than children breastfed with the
      lowest levels of LA. CONCLUSION: Our findings suggest that too high levels of LA
      in colostrum are associated with poorer child development at 2 and 3 y.

PMID- 25760552
TI  - Fluconazole treatment of intrauterine Candida albicans infection in fetal sheep.
AB  - BACKGROUND: Intrauterine Candida albicans infection causes severe fetal
      inflammatory responses and fetal injury in an ovine model. We hypothesized that
      intra-amniotic antifungal therapy with fluconazole would decrease the adverse
      fetal effects of intra-amniotic C. albicans in sheep. METHODS: Sheep received an
      intra-amniotic injection of 10(7) colony-forming units C. albicans. After 2 d,
      animals were then randomized to: (i) intra-amniotic and fetal intraperitoneal
      saline with delivery after 24 h (3 d C. albicans group); (ii) intra-amniotic and
      fetal intraperitoneal injections of fluconazole with delivery after either 24 h
      (3 d C. albicans plus 1 d fluconazole group) or 72 h (5 d C. albicans plus 3 d
      fluconazole group). Controls received intra-amniotic injections of saline
      followed by intra-amniotic and fetal intraperitoneal fluconazole injections.
      RESULTS: Intra-amniotic C. albicans caused severe fetal inflammatory responses
      characterized by decreases in lymphocytes and platelets, an increase in posterior
      mediastinal lymph node weight and proinflammatory mRNA responses in the fetal
      lung, liver, and spleen. Fluconazole treatment temporarily decreased the
      pulmonary and chorioamnion inflammatory responses. CONCLUSION: The severe fetal
      inflammatory responses caused by intra-amniotic C. albicans infection were
      transiently decreased with fluconazole. A timely fetal delivery of antimicrobial
      agents may prevent fetal injury associated with intrauterine infection.

PMID- 25760553
TI  - A possible link between early probiotic intervention and the risk of
      neuropsychiatric disorders later in childhood: a randomized trial.
AB  - BACKGROUND: Recent experimental evidence suggests that gut microbiota may alter
      function within the nervous system providing new insight on the mechanism of
      neuropsychiatric disorders. METHODS: Seventy-five infants who were randomized to
      receive Lactobacillus rhamnosus GG (ATCC 53103) or placebo during the first 6 mo
      of life were followed-up for 13 y. Gut microbiota was assessed at the age of 3
      wk, 3, 6, 12, 18, 24 mo, and 13 y using fluorescein in situ hybridization (FISH)
      and qPCR, and indirectly by determining the blood group secretor type at the age
      of 13 y. The diagnoses of attention deficit hyperactivity disorder (ADHD) and
      Asperger syndrome (AS) by a child neurologist or psychiatrist were based on ICD
      10 diagnostic criteria. RESULTS: At the age of 13 y, ADHD or AS was diagnosed in
      6/35 (17.1%) children in the placebo and none in the probiotic group (P = 0.008).
      The mean (SD) numbers of Bifidobacterium species bacteria in feces during the
      first 6 mo of life was lower in affected children 8.26 (1.24) log cells/g than in
      healthy children 9.12 (0.64) log cells/g; P = 0.03. CONCLUSION: Probiotic
      supplementation early in life may reduce the risk of neuropsychiatric disorder
      development later in childhood possible by mechanisms not limited to gut
      microbiota composition.

PMID- 25760554
TI  - Treatment of melasma in men with low-fluence Q-switched neodymium-doped yttrium
      aluminum-garnet laser versus combined laser and glycolic acid peeling.
AB  - BACKGROUND: Low-fluence Q-switched neodymium-doped yttrium-aluminum-garnet 1,064
      nm laser (LFQS) and glycolic acid (GA) peeling have been reported as a treatment
      option for melasma. However, there are limited data on their efficacy in men.
      OBJECTIVE: To compare the efficacy and safety of LFQS monotherapy with combined
      LFQS and 30% GA peeling in male patients with melasma. MATERIALS AND METHODS:
      Fifteen males with mixed type melasma were randomized to receive 5 weekly
      sessions of LFQS on one side of the face and LFQS plus 30% GA peeling on the
      contralateral side and were followed for 12 weeks. Twelve patients completed the
      protocol. RESULTS: Mean relative lightness index (RL*I) of the combined treatment
      side was lowered throughout the study period, with the maximal improvement of
      52.3% reduction at the fourth week follow-up (p = .023). Patient self-assessment
      was favorable in the combined treatment. However, the mean RL*I increased at 8
      and 12 weeks of follow-up. One subject (8.3%) developed guttate hypopigmentation,
      which did not resolve by the 12-week follow-up. CONCLUSION: Low-fluence Q
      switched neodymium-doped yttrium-aluminum-garnet 1,064-nm laser combined with GA
      peeling temporarily reduced melasma in men, but the incidence of side effects
      does not justify the short-lived benefits of this procedure. This technique
      requires further study.

PMID- 25760555
TI  - Effect of 27-MHz radiofrequency on hair follicles: histological evaluation of
      skin treated ex vivo.
AB  - BACKGROUND: A multitude of methods and treatments exist for cosmetic hair
      removal. Electroepilation is a commonly performed method of hair removal that is
      so-called "permanent"; however, there is a paucity of histological studies of the
      effects of radiofrequency (RF) on hair follicles. OBJECTIVE: This study aimed to
      observe the destruction of human hair follicles and surrounding tissue after the
      treatment with 27.12-MHz RF, with more attention paid to the thermal destruction
      of bulge and bulb/dermal papilla. METHODS: Human scalp specimens obtained during
      face-lift surgery were treated with 27.12-MHz RF. The probe tip was inserted into
      hair follicle, RF current was applied, and treated specimens were processed for
      histological analysis. RESULTS: Significant damages were observed on treated hair
      follicles. Thermal damage was lance-shaped and extended over several hundred
      micrometers (100-400 MUm). The location of destruction areas varied, likely
      depending on the point of insertion of the probe. The epidermis remained intact.
      CONCLUSION: This study shows that the general mechanism of thermolysis is to
      generate damage to cells and tissues surrounding the insertion point of the
      filament. The results suggest that if the insertion point is close to the bulge
      region, there is a risk to destroy hair follicle epithelial stem cells.

PMID- 25760556
TI  - Treatment of acquired and small congenital melanocytic nevi with combined Er: YAG
      laser and long-pulsed alexandrite laser in Asian skin.
AB  - BACKGROUND: There is no gold standard for the treatment of benign melanocytic
      nevi for cosmetic purposes. OBJECTIVE: To investigate the efficacy and safety of
      combined treatment with the short-pulsed erbium:yttrium-aluminum-garnet (Er:YAG)
      and long-pulsed alexandrite laser for acquired melanocytic nevi (AMN) and small
      congenital melanocytic nevi (CMN). METHODS: Fifty-eight AMN and 7 small CMN in 24
      Korean patients were treated with Er:YAG laser followed by long-pulsed
      alexandrite laser at 1-month intervals. RESULTS: At 8 weeks after the final
      treatment, all treated nevi showed complete removal of pigmentation, and the mean
      overall improvement score assessed by physicians, with a quartile grading scale,
      was 3.6 +/- 0.7. The mean number of treatment sessions required to treat CMN (1.5
      +/- 0.3) was significantly greater than that for junctional (1.1 +/- 0.2) or
      compound (1.2 +/- 0.5) AMN. Postinflammatory hyperpigmentation (4.6%), erythema
      (9.2%), hypertrophic scars (1.5%), and mild atrophic scars (10.8%) were observed,
      but all resolved within 6 months, except for hypertrophic scars and 1 atrophic
      scar. Recurrence of pigmentation was observed in 1 CMN (1.5%) during 6 months of
      follow-up. CONCLUSION: Combined treatment with Er:YAG laser and long-pulsed
      alexandrite laser is effective for the removal of small benign melanocytic nevi
      with minimal adverse effects and low recurrence rates.

PMID- 25760557
TI  - Family history of skin cancer is associated with increased risk of cutaneous
      squamous cell carcinoma.
AB  - BACKGROUND: The contribution of family history to cutaneous squamous cell
      carcinoma (SCC) risk has not been systematically quantified. OBJECTIVE: To
      examine the association between self-reported family history of skin cancer and
      SCC risk. METHODS AND MATERIALS: Cases (n = 415) with a pathology-verified SCC
      and 415 age-, gender-, and race-matched controls were identified within a large
      integrated health care delivery system. Family history and skin cancer risk
      factors were ascertained by survey. Odds ratios (ORs) for associations of SCC
      with family history of skin cancer were estimated using conditional logistic
      regression adjusted for environmental and innate SCC risk factors. RESULTS: Any
      known family history of skin cancer was associated with a four-fold higher risk
      of SCC, adjusting for known environmental and innate SCC risk factors (OR, 4.0;
      confidence interval [CI]: 2.5-6.5). An unknown family history of skin cancer
      showed similar risk for SCC (OR, 3.9; CI: 2.4-6.5). In models including skin
      cancer type, the strongest association was for family history of basal cell
      carcinoma (OR, 9.8; CI: 2.6-36.8) and for multiple skin cancer types (OR, 10.5;
      CI: 3.7-29.6). CONCLUSION: Family history of skin cancer is an important
      independent risk factor for cutaneous SCCs.

PMID- 25760558
TI  - Treatment of nevus of ota with a picosecond 755-nm alexandrite laser.

PMID- 25760559
TI  - Biopsy site selfies--a quality improvement pilot study to assist with correct
      surgical site identification.
AB  - BACKGROUND: Determining the biopsy site location of a skin cancer before
      treatment is often challenging. OBJECTIVE: To study the implementation and
      effectiveness of biopsy site selfies as a quality improvement measure for correct
      surgical site identification. MATERIALS AND METHODS: In the first phase, the
      ability of dermatologic surgeon and patient to definitively identify the biopsy
      site and whether photography was needed to ensure site agreement were recorded.
      In the second phase, patients were requested to take biopsy site selfies, and
      after implementation, similar data were collected including whether a biopsy site
      selfie was helpful for definitive site identification. RESULTS: In the first
      phase, the physician and patient were unable to identify the biopsy site 17.6%
      (49/278) and 25.5% (71/278) of cases, respectively. A photograph was needed in
      22.7% of cases (63/278). After implementation of biopsy site selfies, the
      physician and patient were unable to identify the biopsy site 17.4% (23/132) and
      15.2% (20/132) of cases, respectively. Biopsy site selfies were available for
      64.1% of cases for which no internal image was available and critical for site
      identification in 21.4% of these cases. CONCLUSION: Biopsy site selfies has
      proven to be helpful for correct surgical site identification by both the
      physician and the patient and may also provide further reassurance and confidence
      for patients.

PMID- 25760562
TI  - Thermodynamic and spectroscopic properties of oxygen on silver under an oxygen
      atmosphere.
AB  - We report on a combined density functional theory and the experimental study of
      the O1s binding energies and X-ray Absorption Near Edge Structure (XANES) of a
      variety of oxygen species on Ag(111) and Ag(110) surfaces. Our theoretical
      spectra agree with our measured results for known structures, including the p(N*
      1) reconstruction of the Ag(110) surface and the p(4 * 4) reconstruction of the
      Ag(111) surface. Combining the O1s binding energy and XANES spectra yields unique
      spectroscopic fingerprints, allowing us to show that unreconstructed atomic
      oxygen is likely not present on either surface under equilibrium conditions at
      oxygen chemical potentials typical for ethylene epoxidation. Furthermore, we find
      no adsorbed or dissolved atomic species whose calculated spectroscopic features
      agree with those measured for the oxygen species believed to catalyze the partial
      oxidation of ethylene. 

PMID- 25760560
TI  - Intravenous AAV8 Encoding Urocortin-2 Increases Function of the Failing Heart in
      Mice.
AB  - Urocortin-2 (UCn2) peptide infusion increases cardiac function in patients with
      heart failure, but chronic peptide infusion is cumbersome, is costly, and
      provides only short-term benefits. Gene transfer would circumvent these
      shortcomings. We previously showed that a single intravenous (IV) injection of
      AAV8.UCn2 increases plasma UCn2 and left ventricular (LV) systolic and diastolic
      function for at least 7 months in normal mice. Here we test the hypothesis that
      IV delivery of AAV8.UCn2 increases function of the failing heart. Myocardial
      infarction (MI, by coronary ligation) was used to induce heart failure, which was
      assessed by echocardiography 3 weeks after MI. Mice with LV ejection fraction
      (EF) <25% received IV delivery of AAV8.UCn2 (5*10(11) gc) or saline, and 5 weeks
      later echocardiography showed increased LV EF in mice that received UCn2 gene
      transfer (p=0.01). In vivo physiological studies showed a 2-fold increase in peak
      rate of LV pressure development (LV +dP/dt; p<0.0001) and a 1.6-fold increase in
      peak rate of LV pressure decay (LV -dP/dt; p=0.0007), indicating increased LV
      systolic and diastolic function in treated mice. UCn2 gene transfer was
      associated with increased peak systolic Ca(2+) transient amplitude and rate of
      Ca(2+) decline and increased SERCA2a expression. In addition, UCn2 gene transfer
      reduced Thr286 phosphorylation of Cam kinase II, and increased expression of
      cardiac myosin light chain kinase, findings that would be anticipated to increase
      function of the failing heart. We conclude that a single IV injection of
      AAV8.UCn2 increases function of the failing heart. The simplicity of IV injection
      of a vector encoding a gene with beneficial paracrine effects to increase cardiac
      function is an attractive potential clinical strategy. 

PMID- 25760561
TI  - Long-Term Follow-up Results of the DANTE Trial, a Randomized Study of Lung Cancer
      Screening with Spiral Computed Tomography.
AB  - RATIONALE: Screening for lung cancer with low-dose spiral computed tomography
      (LDCT) has been shown to reduce lung cancer mortality by 20% compared with
      screening with chest X-ray (CXR) in the National Lung Screening Trial, but
      uncertainty remains concerning the efficacy of LDCT screening in a community
      setting. OBJECTIVES: To explore the effect of LDCT screening on lung cancer
      mortality compared with no screening. Secondary endpoints included incidence,
      stage, and resectability rates. METHODS: Male smokers of 20+ pack-years, aged 60
      to 74 years, underwent a baseline CXR and sputum cytology examination and
      received five screening rounds with LDCT or a yearly clinical review only in a
      randomized fashion. MEASUREMENTS AND MAIN RESULTS: A total of 1,264 subjects were
      enrolled in the LDCT arm and 1,186 in the control arm. Their median age was 64.0
      years (interquartile range, 5), and median smoking exposure was 45.0 pack-years.
      The median follow-up was 8.35 years. One hundred four patients (8.23%) were
      diagnosed with lung cancer in the screening arm (66 by CT), 47 of whom (3.71%)
      had stage I disease; 72 control patients (6.07%) were diagnosed with lung cancer,
      with 16 (1.35%) being stage I cases. Lung cancer mortality was 543 per 100,000
      person-years (95% confidence interval, 413-700) in the LDCT arm versus 544 per
      100,000 person-years (95% CI, 410-709) in the control arm (hazard ratio, 0.993;
      95% confidence interval, 0.688-1.433). CONCLUSIONS: Because of its limited
      statistical power, the results of the DANTE (Detection And screening of early
      lung cancer with Novel imaging TEchnology) trial do not allow us to make a
      definitive statement about the efficacy of LDCT screening. However, they
      underline the importance of obtaining additional data from randomized trials with
      intervention-free reference arms before the implementation of population
      screening.

PMID- 25760563
TI  - Non-linear imaging and characterization of atherosclerotic arterial tissue using
      combined SHG and FLIM microscopy.
AB  - Atherosclerosis is one of the leading causes of death in the Western World and
      its characterization is extremely interesting from the diagnostic point of view.
      Here, we employed combined SHG-FLIM microscopy to characterize arterial tissue
      with atherosclerosis. The shorter mean fluorescence lifetime measured within
      plaque depositions (1260 +/- 80 ps) with respect to normal arterial wall (1480 +/
      100 ps) allowed discriminating collagen from lipids. SHG measurements and image
      analysis demonstrated that the normal arterial wall has a more anisotropic Aspect
      Ratio (0.37 +/- 0.02) with respect to plaque depositions (0.61 +/- 0.02) and that
      the correlation length can be used for discriminating collagen fibre bundles (2.0
      +/- 0.6 um) from cholesterol depositions (4.1 +/- 0.6 um). The presented method
      has the potential to find place in a clinical setting as well as to be applied in
      vivo in the near future. Graphic composition of SHG and FLIM images representing
      normal arterial wall and plaque depositions. 

PMID- 25760564
TI  - No survival benefit with empirical vancomycin therapy for coagulase-negative
      staphylococcal bloodstream infections in infants.
AB  - BACKGROUND: Coagulase-negative Staphylococcus (CoNS) is the most common cause of
      bloodstream infections (BSI) in hospitalized infants. CoNS BSI is most reliably
      treated with vancomycin; however, concerns about side effects and promoting
      resistance often delay empirical vancomycin therapy until culture results become
      available. METHODS: All infants with CoNS BSI discharged from 348 neonatal
      intensive care units managed by the Pediatrix Medical Group from 1997 to 2012
      were identified. Empirical vancomycin therapy was defined as vancomycin exposure
      on the day of the first positive blood culture. Delayed vancomycin therapy was
      defined as vancomycin exposure 1-3 days after the first positive blood culture.
      We used multivariable logistic regression with random effects for site to
      evaluate the association between the use of empirical vancomycin therapy versus
      delayed vancomycin therapy and 30-day mortality, controlling for gestational age,
      small-for-gestational age status, postnatal age on the day of the first positive
      culture, oxygen requirement, ventilator support and inotropic support on the day
      the first positive culture was obtained. RESULTS: A total of 4364 infants with
      CoNS BSI were identified; 2848 (65%) were treated with empirical vancomycin. The
      median postnatal age at first positive culture was 14 days (interquartile range:
      9, 21). Unadjusted 30-day mortality was similar for infants treated with
      empirical vancomycin and infants treated with delayed vancomycin therapy
      [166/2848 (6%) vs. 69/1516 (4%); P = 0.08]. There was no significant difference
      in 30-day mortality on multivariable analysis [odds ratio: 1.14 (0.84, 1.56)].
      The median duration of bacteremia was 1 day longer for infants with delayed
      vancomycin therapy [4 days (interquartile range: 2, 6) vs. 3 days (2, 5); P <
      0.0001]. CONCLUSIONS: The median duration of bacteremia was 1 day longer in
      infants with CoNS BSI who received delayed vancomycin therapy. Despite this
      finding, empirical vancomycin therapy for CoNS BSI was not associated with
      improved mortality.

PMID- 25760565
TI  - A randomized, open-label study of the safety and efficacy of switching stavudine
      or zidovudine to tenofovir disoproxil fumarate in HIV-1-infected children with
      virologic suppression.
AB  - BACKGROUND: The safety and efficacy of tenofovir disoproxil fumarate (TDF) in HIV
      1-infected children have not been evaluated in a randomized controlled trial.
      METHODS: Subjects (2 to <16 years) on a stavudine (d4T) or zidovudine (ZDV)
      containing regimen with HIV-1 RNA <400 copies/mL were randomized to either switch
      d4T or ZDV to TDF or continue d4T or ZDV. The primary endpoint was the proportion
      of subjects with HIV-1 RNA < 400 copies/mL at Week 48 with a prespecified
      noninferiority margin of 15%. After the 48-week randomized phase, eligible
      subjects were rolled over to an extension phase. RESULTS: Ninety-seven children
      (48 TDF vs. 49 d4T or ZDV) were randomized and treated. The percent of subjects
      who maintained virologic suppression in the TDF versus d4T or ZDV group at Week
      24 were 93.8% versus 89.8% (difference 4.0%; 95% confidence interval:: -6.9% to
      14.9%) and at Week 48 were 83.3% versus 91.8% (difference: -8.5%; 95% confidence
      interval: -21.5% to 4.5%; missing = failure, intent-to-treat analysis). No
      subjects discontinued study drug because of an adverse event in the 48 weeks of
      randomized phase. Four subjects discontinued TDF because of proximal renal
      tubulopathy in the extension phase. CONCLUSIONS: Our study did not demonstrate
      noninferiority of TDF versus d4T or ZDV at Week 48. Overall safety and
      tolerability of TDF in children were consistent with adults. TDF may be
      considered as an alternative to d4T or ZDV in HIV-infected children.

PMID- 25760566
TI  - Efficacy, safety and pharmacokinetics of tenofovir disoproxil fumarate in
      virologic-suppressed HIV-infected children using weight-band dosing.
AB  - BACKGROUND: Tenofovir disoproxil fumarate (TDF) is approved for children but
      concerns remain about long-term renal and bone toxicity. We evaluated the
      efficacy, safety and pharmacokinetics of TDF in treatment-experienced children
      during 96 weeks. METHODS: This was a prospective, open-label study in HIV
      infected children 3-18 years of age (>=15 kg), with viral suppression on their
      first-line regimen without tenofovir. Children were given
      TDF/lamivudine/efavirenz once daily at entry; TDF was prescribed according to
      weight bands. Age-, gender- and CD4-matched controls receiving TDF-sparing
      regimens were concomitantly enrolled. Tenofovir pharmacokinetic assessment was
      performed at week 4. CD4 counts, HIV-1 RNA viral load and safety assessments were
      determined at baseline, 24, 48 and 96 weeks. RESULTS: Eighty children were
      enrolled (40 per group); 35 (44%) were male. Median age was 12.2 (range 3.1-17.7)
      years. The median administered dose was 214 mg/m. Tenofovir geometric mean AUC0
      24 hours, Cmax and C24 hours were 2.66 [90% confidence interval (CI) 2.49-2.84]
      MUg hours/mL, 0.26 (0.24-0.29) MUg/mL and 0.057 (0.052-0.062) MUg/mL,
      respectively. Estimated glomerular filtration rate did not significantly change
      overtime. The fractional excretion of calcium slightly increased but fractional
      excretion of phosphate was unchanged among children in TDF group. The bone
      mineral density Z score decreased in the first 24 weeks of TDF treatment and was
      stable afterward. The TDF group had lower cholesterol levels (P = 0.001). Thirty
      nine of 40 children remained virologically suppressed. No serious adverse event
      related to tenofovir. CONCLUSION: TDF substitution in children and adolescents
      who were otherwise stable while receiving a first-line nonnucleoside reverse
      transcriptase inhibitor-based regimen achieved adequate exposure without
      clinically significant renal or bone adverse events over 96 weeks. While
      reassuring, these preliminary safety findings may not exclude delayed effects on
      renal function and bone density.

PMID- 25760568
TI  - Staphylococcus aureus retropharyngeal abscess in children.
AB  - A retrospective review of 33 patients comparing community-associated methicillin
      resistant Staphylococcus aureus retropharyngeal abscess (RPA) with community
      associated methicillin-susceptible S. aureus RPA from 2002-2013 at Texas
      Children's Hospital revealed most cases of S. aureus RPA have been due to
      community-associated methicillin-resistant S. aureus, which appears to be
      associated with a more complicated clinical course than RPA caused by community
      associated methicillin-susceptible S. aureus. 

PMID- 25760567
TI  - Pharyngeal colonization by Streptococcus pneumoniae in older children and
      adolescents in a geographical area characterized by relatively limited
      pneumococcal vaccination coverage.
AB  - BACKGROUND: The aim of this study was to evaluate the relation between
      colonization and vaccination status with pneumococcal conjugate vaccine (PCV) in
      older children and adolescents living in an area characterized by relatively
      limited vaccination coverage. METHODS: Oropharyngeal swabs were obtained from
      2076 randomly selected healthy school-age children and adolescents, and the
      extracted genomic DNA was tested for Streptococcus pneumoniae by means of real
      time polymerase chain reaction. All of the positive cases were subsequently
      serotyped, and the association between vaccination status with the heptavalent
      PCV (PCV7) and pneumococcal colonization was determined. RESULTS: S. pneumoniae
      was identified in the oropharyngeal swabs of 1201 subjects (57.9%), and its
      prevalence declined with age (74.9% in subjects aged <10 years, 51.8% in those
      aged 10-14 years and 32.7% in those aged >=15 years; P < 0.001). There were more
      carriers of any pneumococcal serotype, any of the serotypes in PCV7, or any of
      the 6 additional serotypes in 13-valent PCV (PCV13) among the vaccinated than the
      unvaccinated subjects, but no association emerged after adjustment for age and
      other selected covariates. Sub-analyses by serotype and age groups revealed
      significant differences in the case of serotypes 3 and 19A among children aged
      <10 years (odds ratios of 2.03 and 2.18, respectively). CONCLUSIONS: These
      results show the absence of any long-term effect of PCV7 on colonization, and
      raise doubts concerning the recent suggestion to use carriage to evaluate the
      efficacy of PCVs. The high prevalence of carriers in all of the age groups
      independent of previous pneumococcal vaccination indicates that further studies
      are needed to evaluate whether the extensive use of PCVs in healthy older
      children and adolescents might reduce pharyngeal colonization of these subjects
      thereby increasing herd immunity.

PMID- 25760569
TI  - Bordetella petrii sinusitis in an immunocompromised adolescent.

PMID- 25760570
TI  - Epstein-Barr virus-associated pericarditis and pleural effusions in a 4-year-old
      girl.

PMID- 25760571
TI  - Eastern equine encephalitis incubation time periods of 5 and 8 days.

PMID- 25760572
TI  - A cautionary tale about treatment of neonatal enteroviral disease.

PMID- 25760573
TI  - Bradycardia with ribavirin therapy in Crimean-Congo hemorrhagic fever.

PMID- 25760574
TI  - Reply: Bradycardia with ribavirin therapy in Crimean-Congo hemorrhagic fever.

PMID- 25760575
TI  - Distributed Atomic Polarizabilities of Amino Acids and their Hydrogen-Bonded
      Aggregates.
AB  - With the purpose of rational design of optical materials, distributed atomic
      polarizabilities of amino acid molecules and their hydrogen-bonded aggregates are
      calculated in order to identify the most efficient functional groups, able to
      buildup larger electric susceptibilities in crystals. Moreover, we carefully
      analyze how the atomic polarizabilities depend on the one-electron basis set or
      the many-electron Hamiltonian, including both wave function and density
      functional theory methods. This is useful for selecting the level of theory that
      best combines high accuracy and low computational costs, very important in
      particular when using the cluster method to estimate susceptibilities of
      molecular-based materials. 

PMID- 25760576
TI  - Acceleration of vascularized bone tissue-engineered constructs in a large animal
      model combining intrinsic and extrinsic vascularization.
AB  - During the last decades, a range of excellent and promising strategies in Bone
      Tissue Engineering have been developed. However, the remaining major problem is
      the lack of vascularization. In this study, extrinsic and intrinsic
      vascularization strategies were combined for acceleration of vascularization. For
      optimal biomechanical stability of the defect site and simplifying future
      transition into clinical application, a primary stable and approved
      nanostructured bone substitute in clinically relevant size was used. An
      arteriovenous (AV) loop was microsurgically created in sheep and implanted,
      together with the bone substitute, in either perforated titanium chambers
      (intrinsic/extrinsic) for different time intervals of up to 18 weeks or isolated
      Teflon((r)) chambers (intrinsic) for 18 weeks. Over time, magnetic resonance
      imaging and micro-computed tomography (CT) analyses illustrate the dense
      vascularization arising from the AV loop. The bone substitute was completely
      interspersed with newly formed tissue after 12 weeks of intrinsic/extrinsic
      vascularization and after 18 weeks of intrinsic/extrinsic and intrinsic
      vascularization. Successful matrix change from an inorganic to an organic
      scaffold could be demonstrated in vascularized areas with scanning electron
      microscopy and energy dispersive X-ray spectroscopy. Using the intrinsic
      vascularization method only, the degradation of the scaffold and osteoclastic
      activity was significantly lower after 18 weeks, compared with 12 and 18 weeks in
      the combined intrinsic-extrinsic model. Immunohistochemical staining revealed an
      increase in bone tissue formation over time, without a difference between
      intrinsic/extrinsic and intrinsic vascularization after 18 weeks. This study
      presents the combination of extrinsic and intrinsic vascularization strategies
      for the generation of an axially vascularized bone substitute in clinically
      relevant size using a large animal model. The additional extrinsic
      vascularization promotes tissue ingrowth and remodeling processes of the bone
      substitute. Extrinsic vessels contribute to faster vascularization and finally
      anastomose with intrinsic vasculature, allowing microvascular transplantation of
      the bone substitute after a shorter prevascularization time than using the
      intrinsic method only. It can be reasonably assumed that the usage of perforated
      chambers can significantly reduce the time until transplantation of bone
      constructs. Finally, this study paves the way for further preclinical testing for
      proof of the concept as a basis for early clinical applicability. 

PMID- 25760578
TI  - Transitioning between 'the old' and 'the new' long-term care systems.

PMID- 25760579
TI  - The causal effects of home care use on institutional long-term care utilization
      and expenditures.
AB  - Limited evidence exists on whether expanding home care saves money overall or how
      much institutional long-term care can be reduced. This paper estimates the causal
      effect of Medicaid-financed home care services on the costs and utilization of
      institutional long-term care using Medicaid claims data. A unique instrumental
      variable was applied to address the potential bias caused by omitted variables or
      reverse effect of institutional care use. We find that the use of Medicaid
      financed home care services significantly reduced but only partially offset
      utilization and Medicaid expenditures on nursing facility services. A $1000
      increase in Medicaid home care expenditures avoided 2.75 days in nursing
      facilities and reduced annual Medicaid nursing facility costs by $351 among
      people over age 65 when selection bias is addressed. Failure to address selection
      biases would misestimate the substitution and offset effects.

PMID- 25760577
TI  - Lipid metabolism disorders and bone dysfunction--interrelated and mutually
      regulated (review).
AB  - The association between lipid and bone metabolism has become an increasing focus
      of interest in recent years, and accumulating evidence has shown that
      atherosclerosis (AS) and osteoporosis (OP), a disorder of bone metabolism,
      frequently co-exist. Fat and bone are known to share a common progenitor cell:
      Multipotent mesenchymal stem cells (MSC) in the bone marrow (BM), which are able
      to differentiate into various cell phenotypes, including osteoblasts, adipocytes
      and chondrocytes. Laboratory-based and clinical trials have shown that increasing
      adipocytes are accompanied by a decrease in bone mineral density (BMD) and bone
      mass. Statins, lipid-lowering drugs used to treat hyperlipidemia, also provide
      benefit in the treatment of OP. There is thus evidence that the metabolism of
      lipids is correlated with that of bone, and that the two are mutually regulated.
      The present review primarily focuses on the potential association between lipid
      metabolism disturbance and OP, based on biological metabolism, pathophysiological
      processes, results from clinical and experimental animal studies, processes
      involved in the differentiation of adipocytes and osteoblasts, as well as
      pharmacological treatments of these diseases.

PMID- 25760580
TI  - Explaining declining rates of institutional LTC use in the Netherlands: a
      decomposition approach.
AB  - The use of long-term care (LTC) is changing rapidly. In the Netherlands, rates of
      institutional LTC use are falling, whereas homecare use is growing. Are these
      changes attributable to declining disability rates, or has LTC use given
      disability changed? And have institutionalization rates fallen regardless of
      disability level, or has LTC use become better tailored to needs? We answer these
      questions by explaining trends in LTC use for the Dutch 65+ population in the
      period 2000-2008 using a nonlinear variant of the Oaxaca-Blinder decomposition.
      We find that changes in LTC use are not due to shifts in the disability
      distribution but can almost entirely be traced back to changes in the way the
      system treats disability. Elderly with mild disability are more likely to be
      treated at home than before, whereas severely disabled individuals continue to
      receive institutional LTC. As a result, LTC use has become better tailored to the
      needs for such care. This finding suggests that policies that promote LTC in the
      community rather than in institutions can effectively mitigate the consequences
      of population aging on LTC spending.

PMID- 25760581
TI  - Testing the bed-blocking hypothesis: does nursing and care home supply reduce
      delayed hospital discharges?
AB  - Hospital bed-blocking occurs when hospital patients are ready to be discharged to
      a nursing home, but no place is available, so that hospital care acts as a more
      costly substitute for long-term care. We investigate the extent to which greater
      supply of nursing home beds or lower prices can reduce hospital bed-blocking
      using a new Local Authority (LA) level administrative data from England on
      hospital delayed discharges in 2009-2013. The results suggest that delayed
      discharges respond to the availability of care home beds, but the effect is
      modest: an increase in care home beds by 10% (250 additional beds per LA) would
      reduce social care delayed discharges by about 6-9%. We also find strong evidence
      of spillover effects across LAs: more care home beds or fewer patients aged over
      65 years in nearby LAs are associated with fewer delayed discharges.

PMID- 25760582
TI  - Financing long-term care: ex ante, ex post or both?
AB  - This paper attempts to examine the heterogeneity in the public financing of long
      term care (LTC) and the wide-ranging instruments in place to finance LTC
      services. We distinguish and classify the institutional responses to the need for
      LTC financing as ex ante (occurring prior to when the need arises, such as
      insurance) and ex post (occurring after the need arises, such as public sector
      and family financing). Then, we examine country-specific data to ascertain
      whether the two types of financing are complements or substitutes. Finally, we
      examine exploratory cross-national data on public expenditure determinants,
      specifically economic, demographic and social determinants. We show that although
      both ex ante and ex post mechanisms exist in all countries with advanced
      industrial economies and despite the fact that instruments are different across
      countries, ex ante and ex post instruments are largely substitutes for each
      other. Expenditure estimates to date indicate that the public financing of LTC is
      highly sensitive to a country's income, ageing of the population and the
      availability of informal caregiving.

PMID- 25760583
TI  - Family structure and long-term care insurance purchase.
AB  - While it has long been assumed that family structure and potential sources of
      informal care play a large role in the purchase decisions for long-term care
      insurance (LTCI), current empirical evidence is inconclusive. Our study examines
      the relationship between family structure and LTCI purchase and addresses several
      major limitations of the prior literature by using a long panel of data and
      considering modern family relationships, such as the presence of stepchildren. We
      find that family structure characteristics from one's own generation,
      particularly about one's spouse, are associated with purchase, but that few
      family structure attributes from the younger generation have an influence. Family
      factors that may indicate future caregiver supply are negatively associated with
      purchase: having a coresidential child, signaling close proximity, and having a
      currently working spouse, signaling a healthy and able spouse, that long-term
      care planning has not occurred yet or that there is less need for asset
      protection afforded by LTCI. Dynamic factors, such as increasing wealth or
      turning 65, are associated with higher likelihood of LTCI purchase.

PMID- 25760584
TI  - Crowding out of long-term care insurance: evidence from European expectations
      data.
AB  - Long-term care (LTC) is the largest insurable risk that old-age individuals face
      in most western societies. However, the demand for LTC insurance is still
      ostensibly small in comparison with the financial risk. One explanation that has
      received limited support is that expectations of either 'public sector funding'
      and 'family support' crowd out individual incentives to seek insurance. This
      paper aims to investigate further the aforementioned motivational crowding-out
      hypothesis by developing a theoretical model and by drawing on an innovative
      empirical analysis of representative European survey data containing records on
      individual expectations of LTC funding sources (including private insurance,
      social insurance, and the family). The theoretical model predicts that, when
      informal care is treated as exogenously determined, expectations of both state
      support and informal care can potentially crowd out LTC insurance expectations,
      while this is not necessarily the case when informal care is endogenous to
      insurance, as happens when intra-family moral hazard is integrated in the
      insurance decision. We find evidence consistent with the presence of family
      crowding out but no robust evidence of public sector crowding out.

PMID- 25760585
TI  - Informal care motivations and intergenerational transfers in European countries.
AB  - This work sets out to analyze the motivations adult children may have to provide
      informal care, considering the monetary transfers they receive from their
      parents. Traditional motivations, such as altruism and exchange, are matched
      against more recent social bond theories. Our findings indicate that informal
      caregivers receive less frequent and less generous transfers than non-caregivers;
      that is, caregivers are more prone to suppress their self-interested motivations
      in order to prioritize the well being of another person. Additionally, long-term
      public care benefits increase both the probability of receiving a transfer and
      its amount, with this effect being more intense for both the poorest and richest
      households. Our findings suggest that if long-term care benefits are intended to
      increase the recipients' welfare and represent a higher fraction of total income
      for the poorest households, the effectiveness of these long-term care policies
      may be diluted.

PMID- 25760586
TI  - The effect of free personal care for the elderly on informal caregiving.
AB  - Population forecasters have predicted that the proportion of people in the UK
      aged 65 years and older will rise significantly in coming decades. This shift in
      demographics will put increasing pressure on the National Health Service and
      providers of social care. However, older people do not rely only on care provided
      by the state; informal care of the elderly is often supplied by family and
      friends. Therefore, the relationship between formal and informal care and the
      reaction of informal carers to institutional changes is an important policy
      issue. This study uses individual level data from the British Household Panel
      Survey to estimate the effects of the introduction of free personal care for the
      elderly in Scotland on informal care behaviour. As the change in policy applied
      only to Scotland, a natural experiment is formed allowing a difference-in
      differences approach to be used. This paper finds that the introduction of the
      policy increased the probability of women supplying informal care by around six
      percentage points. In addition, for both sexes, it reports evidence of a shift
      away from the upper and lower tails towards the middle of the hours of care
      distribution as a result of the change in policy.

PMID- 25760587
TI  - Practice patterns among entrants and incumbents in the home health market after
      the prospective payment system was implemented.
AB  - Home health care expenditures were the fastest growing part of Medicare from 2001
      2009, despite the implementation of prospective payment. Prior research has shown
      that home health agencies adopted two specific strategies to take advantage of
      Medicare policies: provide at least 10 therapy visits to get an enormous marginal
      payment and recertify patients for additional episodes. We study whether there is
      heterogeneity in the adoption of those strategic behaviors between home health
      agency entrants and incumbents and find that entrants were more likely to adopt
      strategic practice patterns than were incumbents. We also find that for-profit
      incumbents mimicked one of the practice patterns following entrants in the same
      market. Our findings suggest that it is important to understand the heterogeneity
      in providers' behavior and how firms interact with each other in the same market.
      These findings help explain the rapid rise in expenditures in the home health
      care market.

PMID- 25760588
TI  - The determinants of care home closure.
AB  - This study investigates the causes of full closure of care homes in the English
      care home/nursing home market. We develop theoretical arguments about two causes
      for closure that are triggered by errors or external shocks: poor economic
      sustainability and regulatory action. Homes aiming to operate with lower quality
      in the market are argued for a number of reasons to be more susceptible to
      errors/shocks in setting quality, especially negative errors, leading to an
      empirical hypothesis that observed quality should negatively affect closure
      chance. In addition, given quality, homes facing relatively high levels of local
      competition should also have an increased chance of closure. We use a panel of
      care homes from 2008 and 2010 to examine factors affecting their closure status
      in subsequent years. We allow for the potential endogeneity of home quality and
      use multiple imputation to replace missing data. Results suggest that homes with
      comparatively higher quality and/or lower levels of competition have less chance
      of closure than other homes. We discuss that the results provide some support for
      the policy of regulators providing quality information to potential purchasers in
      the market.

PMID- 25760589
TI  - Local variability in long-term care services: local autonomy, exogenous
      influences and policy spillovers.
AB  - In many countries, public responsibility over the funding and provision of long
      term care services is held at the local level. In such systems, long-term care
      provision is often characterised by significant local variability. Using a panel
      dataset of local authorities over the period 2002-2012, the paper investigates
      the underlying causes of variation in gross social care expenditure for older
      people in England. The analysis distinguishes between factors outside the direct
      control of policy makers, local preferences and local policy spillovers. The
      results indicate that local demand and supply factors, and to a much lesser
      extent local political preferences and spatial policy spillovers, explain a large
      majority of the observed variation in expenditure.

PMID- 25760590
TI  - Oncotropic H-1 parvovirus infection degrades HIF-1alpha protein in human
      pancreatic cancer cells independently of VHL and RACK1.
AB  - Overexpression of HIF-1alpha, a transcription factor responsive to hypoxia, is
      frequently observed in malignant tumors, which sometimes show resistance to
      chemotherapy and radiation therapy. Consequently, decrease of HIF-1alpha through
      virotherapy offers a logical strategy for the treatment of aggressive tumors. In
      this study, we found that infection with the oncolytic H-1 parvovirus decreased
      HIF-1alpha protein levels in pancreatic cancer cells under CoCl2 or hypoxia. The
      H-1 virus-induced decrease of HIF-1alpha was regulated by a proteasome-mediated
      pathway. Suppression of VHL, an E3 ligase and a critical regulator of HIF-1alpha,
      or enforced expression of UCP, an E2 ubiquitin-conjugating enzyme, failed to
      inhibit the H-1 virus-induced decrease of HIF-1alpha. Furthermore, siRNA-mediated
      suppression of RACK1, another regulator of HIF-1alpha, did not prevent H-1 viral
      infection from lowering HIF-1alpha protein levels. Although decrease of HIF
      1alpha was observed after H-1 viral infection, constitutive expression of HIF
      1alpha limited H-1 viral replication. After combined treatment with H-1
      parvovirus and YC-1, an inhibitor of HIF-1alpha, the apoptosis of pancreatic
      cancer cells was greater than after treatment with H-1 virus alone or YC-1 alone.
      Accordingly, we propose that H-1 parvovirus could be used with YC-1 as a
      potential therapeutic agent against aggressive tumors exhibiting hypoxia and
      increased levels of HIF-1alpha.

PMID- 25760591
TI  - Mycobacteriophages: an important tool for the diagnosis of Mycobacterium
      tuberculosis (review).
AB  - The prevention and control of tuberculosis (TB) on a global scale has become
      increasingly important with the emergence of multidrug-resistant TB.
      Mycobacterium tuberculosis phages have been identified as an important
      investigative tool. Phage genomes exhibit a significant level of diversity and
      mosaic genome architecture, however, they are simple structures, which are
      amenable to genetic manipulation. Based on these characteristics, the phages may
      be used to construct a shuttle plasmid, which is an indispensable tool in the
      investigation of TB. Furthermore, they may be used for rapid diagnosis and
      assessing drug susceptibility of TB, including phage amplified assessment and
      reporter phage technology. With an improved understanding of mycobacteriophages,
      further clarification of the pathogenesis of TB, and of the implications for its
      diagnosis and therapy, may be elucidated.

PMID- 25760592
TI  - The structure of bradyzoite-specific enolase from Toxoplasma gondii reveals
      insights into its dual cytoplasmic and nuclear functions.
AB  - In addition to catalyzing a central step in glycolysis, enolase assumes a
      remarkably diverse set of secondary functions in different organisms, including
      transcription regulation as documented for the oncogene c-Myc promoter-binding
      protein 1. The apicomplexan parasite Toxoplasma gondii differentially expresses
      two nuclear-localized, plant-like enolases: enolase 1 (TgENO1) in the latent
      bradyzoite cyst stage and enolase 2 (TgENO2) in the rapidly replicative
      tachyzoite stage. A 2.75 A resolution crystal structure of bradyzoite enolase 1,
      the second structure to be reported of a bradyzoite-specific protein in
      Toxoplasma, captures an open conformational state and reveals that distinctive
      plant-like insertions are located on surface loops. The enolase 1 structure
      reveals that a unique residue, Glu164, in catalytic loop 2 may account for the
      lower activity of this cyst-stage isozyme. Recombinant TgENO1 specifically binds
      to a TTTTCT DNA motif present in the cyst matrix antigen 1 (TgMAG1) gene promoter
      as demonstrated by gel retardation. Furthermore, direct physical interactions of
      both nuclear TgENO1 and TgENO2 with the TgMAG1 gene promoter are demonstrated in
      vivo using chromatin immunoprecipitation (ChIP) assays. Structural and
      biochemical studies reveal that T. gondii enolase functions are multifaceted,
      including the coordination of gene regulation in parasitic stage development.
      Enolase 1 provides a potential lead in the design of drugs against Toxoplasma
      brain cysts.

PMID- 25760593
TI  - Crystallization of lysozyme with (R)-, (S)- and (RS)-2-methyl-2,4-pentanediol.
AB  - Chiral control of crystallization has ample precedent in the small-molecule
      world, but relatively little is known about the role of chirality in protein
      crystallization. In this study, lysozyme was crystallized in the presence of the
      chiral additive 2-methyl-2,4-pentanediol (MPD) separately using the R and S
      enantiomers as well as with a racemic RS mixture. Crystals grown with (R)-MPD had
      the most order and produced the highest resolution protein structures. This
      result is consistent with the observation that in the crystals grown with (R)-MPD
      and (RS)-MPD the crystal contacts are made by (R)-MPD, demonstrating that there
      is preferential interaction between lysozyme and this enantiomer. These findings
      suggest that chiral interactions are important in protein crystallization. 

PMID- 25760594
TI  - Structural insights into Aspergillus fumigatus lectin specificity: AFL binding
      sites are functionally non-equivalent.
AB  - The Aspergillus fumigatus lectin AFL was recently described as a new member of
      the AAL lectin family. As a lectin from an opportunistic pathogen, it might play
      an important role in the interaction of the pathogen with the human host. A
      detailed study of structures of AFL complexed with several monosaccharides and
      oligosaccharides, including blood-group epitopes, was combined with affinity data
      from SPR and discussed in the context of previous findings. Its six binding sites
      are non-equivalent, and owing to minor differences in amino-acid composition they
      exhibit a marked difference in specific ligand recognition. AFL displays a high
      affinity in the micromolar range towards oligosaccharides which were detected in
      plants and also those bound on the human epithelia. All of these results indicate
      AFL to be a complex member of the lectin family and a challenging target for
      future medical research and, owing to its binding properties, a potentially
      useful tool in specific biotechnological applications. 

PMID- 25760595
TI  - Genuine open form of the pentameric ligand-gated ion channel GLIC.
AB  - Pentameric ligand-gated ion channels (pLGICs) mediate fast chemical
      neurotransmission of nerve signalling in the central and peripheral nervous
      systems. GLIC is a bacterial homologue of eukaryotic pLGIC, the X-ray structure
      of which has been determined in three different conformations. GLIC is thus
      widely used as a model to study the activation and the allosteric transition of
      this family of receptors. The recently solved high-resolution structure of GLIC
      (2.4 A resolution) in the active state revealed two bound acetate molecules in
      the extracellular domain (ECD). Here, it is shown that these two acetates exactly
      overlap with known sites of pharmacological importance in pLGICs, and their
      potential influence on the structure of the open state is studied in detail.
      Firstly, experimental evidence is presented for the correct assignment of these
      acetate molecules by using the anomalous dispersion signal of bromoacetate.
      Secondly, the crystal structure of GLIC in the absence of acetate was solved and
      it is shown that acetate binding induces local conformational changes that occur
      in strategic sites of the ECD. It is expected that this acetate-free structure
      will be useful in future computational studies of the gating transition in GLIC
      and other pLGICs. 

PMID- 25760596
TI  - Catalytically distinct states captured in a crystal lattice: the substrate-bound
      and scavenger states of acylaminoacyl peptidase and their implications for
      functionality.
AB  - Acylaminoacyl peptidase (AAP) is an oligopeptidase that only cleaves short
      peptides or protein segments. In the case of AAP from Aeropyrum pernix (ApAAP),
      previous studies have led to a model in which the clamshell-like opening and
      closing of the enzyme provides the means of substrate-size selection. The closed
      form of the enzyme is catalytically active, while opening deactivates the
      catalytic triad. The crystallographic results presented here show that the open
      form of ApAAP is indeed functionally disabled. The obtained crystal structures
      also reveal that the closed form is penetrable to small ligands: inhibitor added
      to the pre-formed crystal was able to reach the active site of the rigidified
      protein, which is only possible through the narrow channel of the propeller
      domain. Molecular-dynamics simulations investigating the structure of the
      complexes formed with longer peptide substrates showed that their binding within
      the large crevice of the closed form of ApAAP leaves the enzyme structure
      unperturbed; however, their accessing the binding site seems more probable when
      assisted by opening of the enzyme. Thus, the open form of ApAAP corresponds to a
      scavenger of possible substrates, the actual cleavage of which only takes place
      if the enzyme is able to re-close. 

PMID- 25760597
TI  - Structural and functional analysis of Hikeshi, a new nuclear transport receptor
      of Hsp70s.
AB  - Hikeshi is a nuclear transport receptor required for cell survival after stress.
      It mediates heat-shock-induced nuclear import of 70 kDa heat-shock proteins
      (Hsp70s) through interactions with FG-nucleoporins (FG-Nups), which are proteins
      in nuclear pore complexes (NPCs). Here, the crystal structure of human Hikeshi is
      presented at 1.8 A resolution. Hikeshi forms an asymmetric homodimer that is
      responsible for the interaction with Hsp70s. The asymmetry of Hikeshi arises from
      the distinct conformation of the C-terminal domain (CTD) and the flexibility of
      the linker regions of each monomer. Structure-guided mutational analyses showed
      that both the flexible linker region and the CTD are important for nuclear import
      of Hsp70. Pull-down assays revealed that only full-length Hsp70s can interact
      with Hikeshi. The N-terminal domain (NTD) consists of a jelly-roll/beta-sandwich
      fold structure which contains hydrophobic pockets involved in FG-Nup recognition.
      A unique extended loop (E-loop) in the NTD is likely to regulate the interactions
      of Hikeshi with FG-Nups. The crystal structure of Hikeshi explains how Hikeshi
      participates in the regulation of nuclear import through the recognition of FG
      Nups and which part of Hikeshi affects its binding to Hsp70. This study is the
      first to yield structural insight into this highly unique import receptor. 

PMID- 25760598
TI  - Three-dimensional structures of Plasmodium falciparum spermidine synthase with
      bound inhibitors suggest new strategies for drug design.
AB  - The enzymes of the polyamine-biosynthesis pathway have been proposed to be
      promising drug targets in the treatment of malaria. Spermidine synthase (SpdS;
      putrescine aminopropyltransferase) catalyzes the transfer of the aminopropyl
      moiety from decarboxylated S-adenosylmethionine to putrescine, leading to the
      formation of spermidine and 5'-methylthioadenosine (MTA). In this work, X-ray
      crystallography was used to examine ligand complexes of SpdS from the malaria
      parasite Plasmodium falciparum (PfSpdS). Five crystal structures were determined
      of PfSpdS in complex with MTA and the substrate putrescine, with MTA and
      spermidine, which was obtained as a result of the enzymatic reaction taking place
      within the crystals, with dcAdoMet and the inhibitor 4-methylaniline, with MTA
      and 4-aminomethylaniline, and with a compound predicted in earlier in silico
      screening to bind to the active site of the enzyme, benzimidazol-(2-yl)pentan-1
      amine (BIPA). In contrast to the other inhibitors tested, the complex with BIPA
      was obtained without any ligand bound to the dcAdoMet-binding site of the enzyme.
      The complexes with the aniline compounds and BIPA revealed a new mode of ligand
      binding to PfSpdS. The observed binding mode of the ligands, and the interplay
      between the two substrate-binding sites and the flexible gatekeeper loop, can be
      used in the design of new approaches in the search for new inhibitors of SpdS. 

PMID- 25760599
TI  - Interaction of the amyloid precursor protein-like protein 1 (APLP1) E2 domain
      with heparan sulfate involves two distinct binding modes.
AB  - Beyond the pathology of Alzheimer's disease, the members of the amyloid precursor
      protein (APP) family are essential for neuronal development and cell homeostasis
      in mammals. APP and its paralogues APP-like protein 1 (APLP1) and APP-like
      protein 2 (APLP2) contain the highly conserved heparan sulfate (HS) binding
      domain E2, which effects various (patho)physiological functions. Here, two
      crystal structures of the E2 domain of APLP1 are presented in the apo form and in
      complex with a heparin dodecasaccharide at 2.5 A resolution. The apo structure of
      APLP1 E2 revealed an unfolded and hence flexible N-terminal helix alphaA. The
      (APLP1 E2)2-(heparin)2 complex structure revealed two distinct binding modes,
      with APLP1 E2 explicitly recognizing the heparin terminus but also interacting
      with a continuous heparin chain. The latter only requires a certain register of
      the sugar moieties that fits to a positively charged surface patch and
      contributes to the general heparin-binding capability of APP-family proteins.
      Terminal binding of APLP1 E2 to heparin specifically involves a structure of the
      nonreducing end that is very similar to heparanase-processed HS chains. These
      data reveal a conserved mechanism for the binding of APP-family proteins to HS
      and imply a specific regulatory role of HS modifications in the biology of APP
      and APP-like proteins. 

PMID- 25760601
TI  - The mechanism of substrate-controlled allosteric regulation of SAMHD1 activated
      by GTP.
AB  - SAMHD1 is the only known eukaryotic deoxynucleoside triphosphate
      triphosphohydrolase (dNTPase) and is a major regulator of intracellular dNTP
      pools. It has been reported to be a potent inhibitor of retroviruses such as HIV
      1 and endogenous retrotransposons. Previous crystal structures have revealed that
      SAMHD1 is activated by dGTP-dependent tetramer formation. However, recent data
      have indicated that the primary activator of SAMHD1 is GTP, not dGTP. Therefore,
      how its dNTPase activity is regulated needs to be further clarified. Here, five
      crystal structures of the catalytic core of SAMHD1 in complex with different
      combinations of GTP and dNTPs are reported, including a GTP-bound dimer and four
      GTP/dNTP-bound tetramers. The data show that human SAMHD1 contains two unique
      activator-binding sites in the allosteric pocket. The primary activator GTP binds
      to one site and the substrate dNTP (dATP, dCTP, dUTP or dTTP) occupies the other.
      Consequently, both GTP and dNTP are required for tetramer activation of the
      enzyme. In the absence of substrate binding, SAMHD1 adopts an inactive dimer
      conformation even when complexed with GTP. Furthermore, SAMHD1 activation is
      regulated by the concentration of dNTP. Thus, the level of dNTP pools is
      elegantly regulated by the self-sensing ability of SAMHD1 through a novel
      activation mechanism. 

PMID- 25760602
TI  - The 1.65 A resolution structure of the complex of AZD4547 with the kinase domain
      of FGFR1 displays exquisite molecular recognition.
AB  - The fibroblast growth factor receptor (FGFR) family are expressed widely in
      normal tissues and play a role in tissue repair, inflammation, angiogenesis and
      development. However, aberrant signalling through this family can lead to
      cellular proliferation, evasion of apoptosis and induction of angiogenesis, which
      is implicated in the development of many cancers and also in drug resistance. The
      high frequency of FGFR amplification or mutation in multiple cancer types is such
      that this family has been targeted for the discovery of novel, selective drug
      compounds, with one of the most recently discovered being AZD4547, a subnanomolar
      (IC50) FGFR1 inhibitor developed by AstraZeneca and currently in clinical trials.
      The 1.65 A resolution crystal structure of AZD4547 bound to the kinase domain of
      FGFR1 has been determined and reveals extensive drug-protein interactions, an
      integral network of water molecules and the tight closure of the FGFR1 P-loop to
      form a long, narrow crevice in which the AZD4547 molecule binds. 

PMID- 25760600
TI  - A disulfide-bond cascade mechanism for arsenic(III) S-adenosylmethionine
      methyltransferase.
AB  - Methylation of the toxic metalloid arsenic is widespread in nature. Members of
      every kingdom have arsenic(III) S-adenosylmethionine (SAM) methyltransferase
      enzymes, which are termed ArsM in microbes and AS3MT in animals, including
      humans. Trivalent arsenic(III) is methylated up to three times to form
      methylarsenite [MAs(III)], dimethylarsenite [DMAs(III)] and the volatile
      trimethylarsine [TMAs(III)]. In microbes, arsenic methylation is a detoxification
      process. In humans, MAs(III) and DMAs(III) are more toxic and carcinogenic than
      either inorganic arsenate or arsenite. Here, new crystal structures are reported
      of ArsM from the thermophilic eukaryotic alga Cyanidioschyzon sp. 5508 (CmArsM)
      with the bound aromatic arsenicals phenylarsenite [PhAs(III)] at 1.80 A
      resolution and reduced roxarsone [Rox(III)] at 2.25 A resolution. These
      organoarsenicals are bound to two of four conserved cysteine residues: Cys174 and
      Cys224. The electron density extends the structure to include a newly identified
      conserved cysteine residue, Cys44, which is disulfide-bonded to the fourth
      conserved cysteine residue, Cys72. A second disulfide bond between Cys72 and
      Cys174 had been observed previously in a structure with bound SAM. The loop
      containing Cys44 and Cys72 shifts by nearly 6.5 A in the arsenic(III)-bound
      structures compared with the SAM-bound structure, which suggests that this
      movement leads to formation of the Cys72-Cys174 disulfide bond. A model is
      proposed for the catalytic mechanism of arsenic(III) SAM methyltransferases in
      which a disulfide-bond cascade maintains the products in the trivalent state. 

PMID- 25760603
TI  - Automating the application of smart materials for protein crystallization.
AB  - The fabrication and validation of the first semi-liquid nonprotein nucleating
      agent to be administered automatically to crystallization trials is reported.
      This research builds upon prior demonstration of the suitability of molecularly
      imprinted polymers (MIPs; known as 'smart materials') for inducing protein
      crystal growth. Modified MIPs of altered texture suitable for high-throughput
      trials are demonstrated to improve crystal quality and to increase the
      probability of success when screening for suitable crystallization conditions.
      The application of these materials is simple, time-efficient and will provide a
      potent tool for structural biologists embarking on crystallization trials. 

PMID- 25760604
TI  - Structure of a highly acidic beta-lactamase from the moderate halophile
      Chromohalobacter sp. 560 and the discovery of a Cs(+)-selective binding site.
AB  - Environmentally friendly absorbents are needed for Sr(2+) and Cs(+), as the
      removal of the radioactive Sr(2+) and Cs(+) that has leaked from the Fukushima
      Nuclear Power Plant is one of the most important problems in Japan. Halophilic
      proteins are known to have many acidic residues on their surface that can provide
      specific binding sites for metal ions such as Cs(+) or Sr(2+). The crystal
      structure of a halophilic beta-lactamase from Chromohalobacter sp. 560 (HaBLA)
      was determined to resolutions of between 1.8 and 2.9 A in space group P31 using X
      ray crystallography. Moreover, the locations of bound Sr(2+) and Cs(+) ions were
      identified by anomalous X-ray diffraction. The location of one Cs(+)-specific
      binding site was identified in HaBLA even in the presence of a ninefold molar
      excess of Na(+) (90 mM Na(+)/10 mM Cs(+)). From an activity assay using
      isothermal titration calorimetry, the bound Sr(2+) and Cs(+) ions do not
      significantly affect the enzymatic function of HaBLA. The observation of a
      selective and high-affinity Cs(+)-binding site provides important information
      that is useful for the design of artificial Cs(+)-binding sites that may be
      useful in the bioremediation of radioactive isotopes. 

PMID- 25760605
TI  - Structures of the human Pals1 PDZ domain with and without ligand suggest gated
      access of Crb to the PDZ peptide-binding groove.
AB  - Many components of epithelial polarity protein complexes possess PDZ domains that
      are required for protein interaction and recruitment to the apical plasma
      membrane. Apical localization of the Crumbs (Crb) transmembrane protein requires
      a PDZ-mediated interaction with Pals1 (protein-associated with Lin7, Stardust,
      MPP5), a member of the p55 family of membrane-associated guanylate kinases
      (MAGUKs). This study describes the molecular interaction between the Crb carboxy
      terminal motif (ERLI), which is required for Drosophila cell polarity, and the
      Pals1 PDZ domain using crystallography and fluorescence polarization. Only the
      last four Crb residues contribute to Pals1 PDZ-domain binding affinity, with
      specificity contributed by conserved charged interactions. Comparison of the Crb
      bound Pals1 PDZ structure with an apo Pals1 structure reveals a key Phe side
      chain that gates access to the PDZ peptide-binding groove. Removal of this side
      chain enhances the binding affinity by more than fivefold, suggesting that access
      of Crb to Pals1 may be regulated by intradomain contacts or by protein-protein
      interaction. 

PMID- 25760606
TI  - Structures of three polycystic kidney disease-like domains from Clostridium
      histolyticum collagenases ColG and ColH.
AB  - Clostridium histolyticum collagenases ColG and ColH are segmental enzymes that
      are thought to be activated by Ca(2+)-triggered domain reorientation to cause
      extensive tissue destruction. The collagenases consist of a collagenase module
      (s1), a variable number of polycystic kidney disease-like (PKD-like) domains (s2a
      and s2b in ColH and s2 in ColG) and a variable number of collagen-binding domains
      (s3 in ColH and s3a and s3b in ColG). The X-ray crystal structures of Ca(2+)
      bound holo s2b (1.4 A resolution, R = 15.0%, Rfree = 19.1%) and holo s2a (1.9 A
      resolution, R = 16.3%, Rfree = 20.7%), as well as of Ca(2+)-free apo s2a (1.8 A
      resolution, R = 20.7%, Rfree = 27.2%) and two new forms of N-terminally truncated
      apo s2 (1.4 A resolution, R = 16.9%, Rfree = 21.2%; 1.6 A resolution, R = 16.2%,
      Rfree = 19.2%), are reported. The structurally similar PKD-like domains resemble
      the V-set Ig fold. In addition to a conserved beta-bulge, the PKD-like domains
      feature a second bulge that also changes the allegiance of the subsequent beta
      strand. This beta-bulge and the genesis of a Ca(2+) pocket in the archaeal PKD
      like domain suggest a close kinship between bacterial and archaeal PKD-like
      domains. Different surface properties and indications of different dynamics
      suggest unique roles for the PKD-like domains in ColG and in ColH. Surface
      aromatic residues found on ColH s2a-s2b, but not on ColG s2, may provide the weak
      interaction in the biphasic collagen-binding mode previously found in s2b-s3. B
      factor analyses suggest that in the presence of Ca(2+) the midsection of s2
      becomes more flexible but the midsections of s2a and s2b stay rigid. The
      different surface properties and dynamics of the domains suggest that the PKD
      like domains of M9B bacterial collagenase can be grouped into either a ColG
      subset or a ColH subset. The conserved properties of PKD-like domains in ColG and
      in ColH include Ca(2+) binding. Conserved residues not only interact with Ca(2+),
      but also position the Ca(2+)-interacting water molecule. Ca(2+) aligns the N
      terminal linker approximately parallel to the major axis of the domain. Ca(2+)
      binding also increases stability against heat and guanidine hydrochloride, and
      may improve the longevity in the extracellular matrix. The results of this study
      will further assist in developing collagen-targeting vehicles for various signal
      molecules. 

PMID- 25760607
TI  - Four crystal structures of human LLT1, a ligand of human NKR-P1, in varied
      glycosylation and oligomerization states.
AB  - Human LLT1 is a C-type lectin-like ligand of NKR-P1 (CD161, gene KLRB1), a C-type
      lectin-like receptor of natural killer cells. Using X-ray diffraction, the first
      experimental structures of human LLT1 were determined. Four structures of LLT1
      under various conditions were determined: monomeric, dimeric deglycosylated after
      the first N-acetylglucosamine unit in two forms and hexameric with homogeneous
      GlcNAc2Man5 glycosylation. The dimeric form follows the classical dimerization
      mode of human CD69. The monomeric form keeps the same fold with the exception of
      the position of an outer part of the long loop region. The hexamer of
      glycosylated LLT1 consists of three classical dimers. The hexameric packing may
      indicate a possible mode of interaction of C-type lectin-like proteins in the
      glycosylated form. 

PMID- 25760608
TI  - An intermolecular binding mechanism involving multiple LysM domains mediates
      carbohydrate recognition by an endopeptidase.
AB  - LysM domains, which are frequently present as repetitive entities in both
      bacterial and plant proteins, are known to interact with carbohydrates containing
      N-acetylglucosamine (GlcNAc) moieties, such as chitin and peptidoglycan. In
      bacteria, the functional significance of the involvement of multiple LysM domains
      in substrate binding has so far lacked support from high-resolution structures of
      ligand-bound complexes. Here, a structural study of the Thermus thermophilus
      NlpC/P60 endopeptidase containing two LysM domains is presented. The crystal
      structure and small-angle X-ray scattering solution studies of this endopeptidase
      revealed the presence of a homodimer. The structure of the two LysM domains co
      crystallized with N-acetyl-chitohexaose revealed a new intermolecular binding
      mode that may explain the differential interaction between LysM domains and short
      or long chitin oligomers. By combining the structural information with the three
      dimensional model of peptidoglycan, a model suggesting how protein dimerization
      enhances the recognition of peptidoglycan is proposed. 

PMID- 25760609
TI  - Automated de novo phasing and model building of coiled-coil proteins.
AB  - Models generated by de novo structure prediction can be very useful starting
      points for molecular replacement for systems where suitable structural homologues
      cannot be readily identified. Protein-protein complexes and de novo-designed
      proteins are examples of systems that can be challenging to phase. In this study,
      the potential of de novo models of protein complexes for use as starting points
      for molecular replacement is investigated. The approach is demonstrated using
      homomeric coiled-coil proteins, which are excellent model systems for oligomeric
      systems. Despite the stereotypical fold of coiled coils, initial phase estimation
      can be difficult and many structures have to be solved with experimental phasing.
      A method was developed for automatic structure determination of homomeric coiled
      coils from X-ray diffraction data. In a benchmark set of 24 coiled coils, ranging
      from dimers to pentamers with resolutions down to 2.5 A, 22 systems were
      automatically solved, 11 of which had previously been solved by experimental
      phasing. The generated models contained 71-103% of the residues present in the
      deposited structures, had the correct sequence and had free R values that
      deviated on average by 0.01 from those of the respective reference structures.
      The electron-density maps were of sufficient quality that only minor manual
      editing was necessary to produce final structures. The method, named CCsolve,
      combines methods for de novo structure prediction, initial phase estimation and
      automated model building into one pipeline. CCsolve is robust against errors in
      the initial models and can readily be modified to make use of alternative
      crystallographic software. The results demonstrate the feasibility of de novo
      phasing of protein-protein complexes, an approach that could also be employed for
      other small systems beyond coiled coils. 

PMID- 25760610
TI  - X-ray, spectroscopic and normal-mode dynamics of calexcitin: structure-function
      studies of a neuronal calcium-signalling protein.
AB  - The protein calexcitin was originally identified in molluscan photoreceptor
      neurons as a 20 kDa molecule which was up-regulated and phosphorylated following
      a Pavlovian conditioning protocol. Subsequent studies showed that calexcitin
      regulates the voltage-dependent potassium channel and the calcium-dependent
      potassium channel as well as causing the release of calcium ions from the
      endoplasmic reticulum (ER) by binding to the ryanodine receptor. A crystal
      structure of calexcitin from the squid Loligo pealei showed that the fold is
      similar to that of another signalling protein, calmodulin, the N- and C-terminal
      domains of which are known to separate upon calcium binding, allowing
      interactions with the target protein. Phosphorylation of calexcitin causes it to
      translocate to the cell membrane, where its effects on membrane excitability are
      exerted and, accordingly, L. pealei calexcitin contains two protein kinase C
      phosphorylation sites (Thr61 and Thr188). Thr-to-Asp mutations which mimic
      phosphorylation of the protein were introduced and crystal structures of the
      corresponding single and double mutants were determined, which suggest that the C
      terminal phosphorylation site (Thr188) exerts the greatest effects on the protein
      structure. Extensive NMR studies were also conducted, which demonstrate that the
      wild-type protein predominantly adopts a more open conformation in solution than
      the crystallographic studies have indicated and, accordingly, normal-mode dynamic
      simulations suggest that it has considerably greater capacity for flexible motion
      than the X-ray studies had suggested. Like calmodulin, calexcitin consists of
      four EF-hand motifs, although only the first three EF-hands of calexcitin are
      involved in binding calcium ions; the C-terminal EF-hand lacks the appropriate
      amino acids. Hence, calexcitin possesses two functional EF-hands in close
      proximity in its N-terminal domain and one functional calcium site in its C
      terminal domain. There is evidence that the protein has two markedly different
      affinities for calcium ions, the weaker of which is most likely to be associated
      with binding of calcium ions to the protein during neuronal excitation. In the
      current study, site-directed mutagenesis has been used to abolish each of the
      three calcium-binding sites of calexcitin, and these experiments suggest that it
      is the single calcium-binding site in the C-terminal domain of the protein which
      is likely to have a sensory role in the neuron. 

PMID- 25760611
TI  - Crystal structure and enzymatic properties of a broad substrate-specificity
      psychrophilic aminotransferase from the Antarctic soil bacterium Psychrobacter
      sp. B6.
AB  - Aminotransferases (ATs) are enzymes that are commonly used in the chemical and
      pharmaceutical industries for the synthesis of natural and non-natural amino
      acids by transamination reactions. Currently, the easily accessible enzymes from
      mesophilic organisms are most commonly used; however, for economical and
      ecological reasons the utilization of aminotransferases from psychrophiles would
      be more advantageous, as their optimum reaction temperature is usually
      significantly lower than for the mesophilic ATs. Here, gene isolation, protein
      expression, purification, enzymatic properties and structural studies are
      reported for the cold-active aromatic amino-acid aminotransferase (PsyArAT) from
      Psychrobacter sp. B6, a psychrotrophic, Gram-negative strain from Antarctic soil.
      Preliminary computational analysis indicated dual functionality of the enzyme
      through the ability to utilize both aromatic amino acids and aspartate as
      substrates. This postulation was confirmed by enzymatic activity tests, which
      showed that it belonged to the class EC 2.6.1.57. The first crystal structures of
      a psychrophilic aromatic amino-acid aminotransferase have been determined at
      resolutions of 2.19 A for the native enzyme (PsyArAT) and 2.76 A for its complex
      with aspartic acid (PsyArAT/D). Both types of crystals grew in the monoclinic
      space group P21 under slightly different crystallization conditions. The PsyArAT
      crystals contained a dimer (90 kDa) in the asymmetric unit, which corresponds to
      the active form of this enzyme, whereas the crystals of the PsyArAT/D complex
      included four dimers showing different stages of the transamination reaction.

PMID- 25760612
TI  - FEM: feature-enhanced map.
AB  - A method is presented that modifies a 2mFobs - DFmodel sigmaA-weighted map such
      that the resulting map can strengthen a weak signal, if present, and can reduce
      model bias and noise. The method consists of first randomizing the starting map
      and filling in missing reflections using multiple methods. This is followed by
      restricting the map to regions with convincing density and the application of
      sharpening. The final map is then created by combining a series of histogram
      equalized intermediate maps. In the test cases shown, the maps produced in this
      way are found to have increased interpretability and decreased model bias
      compared with the starting 2mFobs - DFmodel sigmaA-weighted map. 

PMID- 25760613
TI  - NuProPlot: nucleic acid and protein interaction analysis and plotting program.
AB  - Growing numbers of protein and nucleic acid complex structures are being
      determined and deposited in the Protein Data Bank and the Nucleic Acid Database.
      With the increasing complexity of these structures, it is challenging to analyse
      and visualize the three-dimensional interactions. The currently available
      programs for such analysis and visualization are limited in their applications.
      They can only analyse a subset of protein-nucleic acid complexes and require
      multiple iterations before obtaining plots that are suitable for presentation. An
      interactive web-based program, NuProPlot (http://www.nuproplot.com), has been
      developed which can automatically identify hydrogen, electrostatic and van der
      Waals interactions between proteins and nucleic acids and generate a plot showing
      all of the interactions. Protein-DNA and protein-RNA interactions can be
      visualized in simple two-dimensional schematics. Interactive schematic drawing
      options allow selection of the plotted area and repositioning of the individual
      interactions for better legibility. NuProPlot is a fully automated and user
      friendly program providing various custom options. NuProPlot represents a greatly
      improved option for analysis and presentation of protein-nucleic acid
      interactions. 

PMID- 25760615
TI  - The structure of apo ArnA features an unexpected central binding pocket and
      provides an explanation for enzymatic cooperativity.
AB  - The bacterial protein ArnA is an essential enzyme in the pathway leading to the
      modification of lipid A with the pentose sugar 4-amino-4-deoxy-L-arabinose. This
      modification confers resistance to polymyxins, which are antibiotics that are
      used as a last resort to treat infections with multiple drug-resistant Gram
      negative bacteria. ArnA contains two domains with distinct catalytic functions: a
      dehydrogenase domain and a transformylase domain. The protein forms homohexamers
      organized as a dimer of trimers. Here, the crystal structure of apo ArnA is
      presented and compared with its ATP- and UDP-glucuronic acid-bound counterparts.
      The comparison reveals major structural rearrangements in the dehydrogenase
      domain that lead to the formation of a previously unobserved binding pocket at
      the centre of each ArnA trimer in its apo state. In the crystal structure, this
      pocket is occupied by a DTT molecule. It is shown that formation of the pocket is
      linked to a cascade of structural rearrangements that emerge from the NAD(+)
      binding site. Based on these findings, a small effector molecule is postulated
      that binds to the central pocket and modulates the catalytic properties of ArnA.
      Furthermore, the discovered conformational changes provide a mechanistic
      explanation for the strong cooperative effect recently reported for the ArnA
      dehydrogenase function. 

PMID- 25760616
TI  - Brickworx builds recurrent RNA and DNA structural motifs into medium- and low
      resolution electron-density maps.
AB  - Brickworx is a computer program that builds crystal structure models of nucleic
      acid molecules using recurrent motifs including double-stranded helices. In a
      first step, the program searches for electron-density peaks that may correspond
      to phosphate groups; it may also take into account phosphate-group positions
      provided by the user. Subsequently, comparing the three-dimensional patterns of
      the P atoms with a database of nucleic acid fragments, it finds the matching
      positions of the double-stranded helical motifs (A-RNA or B-DNA) in the unit
      cell. If the target structure is RNA, the helical fragments are further extended
      with recurrent RNA motifs from a fragment library that contains single-stranded
      segments. Finally, the matched motifs are merged and refined in real space to
      find the most likely conformations, including a fit of the sequence to the
      electron-density map. The Brickworx program is available for download and as a
      web server at http://iimcb.genesilico.pl/brickworx. 

PMID- 25760617
TI  - The rate of cis-trans conformation errors is increasing in low-resolution crystal
      structures.
AB  - Cis-peptide bonds (with the exception of X-Pro) are exceedingly rare in native
      protein structures, yet a check for these is not currently included in the
      standard workflow for some common crystallography packages nor in the automated
      quality checks that are applied during submission to the Protein Data Bank. This
      appears to be leading to a growing rate of inclusion of spurious cis-peptide
      bonds in low-resolution structures both in absolute terms and as a fraction of
      solved residues. Most concerningly, it is possible for structures to contain very
      large numbers (>1%) of spurious cis-peptide bonds while still achieving excellent
      quality reports from MolProbity, leading to concerns that ignoring such errors is
      allowing software to overfit maps without producing telltale errors in, for
      example, the Ramachandran plot. 

PMID- 25760614
TI  - Structure of Csd3 from Helicobacter pylori, a cell shape-determining
      metallopeptidase.
AB  - Helicobacter pylori is associated with various gastrointestinal diseases such as
      gastritis, ulcers and gastric cancer. Its colonization of the human gastric
      mucosa requires high motility, which depends on its helical cell shape. Seven
      cell shape-determining genes (csd1, csd2, csd3/hdpA, ccmA, csd4, csd5 and csd6)
      have been identified in H. pylori. Their proteins play key roles in determining
      the cell shape through modifications of the cell-wall peptidoglycan by the
      alteration of cross-linking or by the trimming of peptidoglycan muropeptides.
      Among them, Csd3 (also known as HdpA) is a bifunctional enzyme. Its D,D
      endopeptidase activity cleaves the D-Ala(4)-mDAP(3) peptide bond between cross
      linked muramyl tetrapeptides and pentapeptides. It is also a D,D-carboxypeptidase
      that cleaves off the terminal D-Ala(5) from the muramyl pentapeptide. Here, the
      crystal structure of this protein has been determined, revealing the organization
      of its three domains in a latent and inactive state. The N-terminal domain 1 and
      the core of domain 2 share the same fold despite a very low level of sequence
      identity, and their surface-charge distributions are different. The C-terminal
      LytM domain contains the catalytic site with a Zn(2+) ion, like the similar
      domains of other M23 metallopeptidases. Domain 1 occludes the active site of the
      LytM domain. The core of domain 2 is held against the LytM domain by the C
      terminal tail region that protrudes from the LytM domain. 

PMID- 25760618
TI  - The structure of the hexameric atrazine chlorohydrolase AtzA.
AB  - Atrazine chlorohydrolase (AtzA) was discovered and purified in the early 1990s
      from soil that had been exposed to the widely used herbicide atrazine. It was
      subsequently found that this enzyme catalyzes the first and necessary step in the
      breakdown of atrazine by the soil organism Pseudomonas sp. strain ADP. Although
      it has taken 20 years, a crystal structure of the full hexameric form of AtzA has
      now been obtained. AtzA is less well adapted to its physiological role (i.e.
      atrazine dechlorination) than the alternative metal-dependent atrazine
      chlorohydrolase (TrzN), with a substrate-binding pocket that is under
      considerable strain and for which the substrate is a poor fit. 

PMID- 25760620
TI  - Snapshots of ligand entry, malleable binding and induced helical movement in P
      glycoprotein.
AB  - P-glycoprotein (P-gp) is a transporter of great clinical and pharmacological
      significance. Several structural studies of P-gp and its homologs have provided
      insights into its transport cycle, but questions remain regarding how P-gp
      recognizes diverse substrates and how substrate binding is coupled to ATP
      hydrolysis. Here, four new P-gp co-crystal structures with a series of rationally
      designed ligands are presented. It is observed that the binding of certain
      ligands, including an ATP-hydrolysis stimulator, produces a large conformational
      change in the fourth transmembrane helix, which is positioned to potentially
      transmit a signal to the nucleotide-binding domains. A new ligand-binding site on
      the surface of P-gp facing the inner leaflet of the membrane is also described,
      providing vital insights regarding the entry mechanism of hydrophobic drugs and
      lipids into P-gp. These results represent significant advances in the
      understanding of how P-gp and related transporters bind and export a plethora of
      metabolites, antibiotics and clinically approved and pipeline drugs. 

PMID- 25760621
TI  - Effects of aging and idiopathic Parkinson's disease on tactile temporal order
      judgment.
AB  - It is generally accepted that the basal ganglia play an important role in
      interval timing that requires the measurement of temporal durations. By contrast,
      it remains controversial whether the basal ganglia play an essential role in
      temporal order judgment (TOJ) of successive stimuli, a behavior that does not
      necessarily require the measurement of durations in time. To address this issue,
      we compared the effects of idiopathic Parkinson's disease (PD) on the TOJ of two
      successive taps delivered to each hand, with the arms uncrossed in one condition
      and crossed in another. In addition to age-matched elderly participants without
      PD (non-PD), we examined young healthy participants so that the effect of aging
      could serve as a control for evaluating the effects of PD. There was no
      significant difference between PD and non-PD participants in any parameter of TOJ
      under either arm posture, although reaction time was significantly longer in PD
      compared with non-PD participants. By contrast, the effect of aging was apparent
      in both conditions. With their arms uncrossed, the temporal resolution (the
      interstimulus interval that yielded 84% correct responses) in elderly
      participants was significantly worse compared with young participants. With their
      arms crossed, elderly participants made more errors at longer intervals (~1 s)
      than young participants, although both age groups showed similar judgment
      reversal at moderately short intervals (~200 ms). These results indicate that the
      basal ganglia and dopaminergic systems do not play essential roles in tactile TOJ
      involving both hands and that the effect of aging on TOJ is mostly independent of
      the dopaminergic systems.

PMID- 25760619
TI  - Structural characterization of substrate and inhibitor binding to farnesyl
      pyrophosphate synthase from Pseudomonas aeruginosa.
AB  - Locus PA4043 in the genome of Pseudomonas aeruginosa PAO1 has been annotated as
      coding for a farnesyl pyrophosphate synthase (FPPS). This open reading frame was
      cloned and expressed recombinantly in Escherichia coli. The dimeric enzyme shows
      farnesyl pyrophosphate synthase activity and is strongly inhibited by ibandronate
      and zoledronate, drugs that are presently in clinical use. The structures of the
      unliganded enzyme and complexes with the substrate geranyl diphosphate (GPP), the
      inhibitor ibandronate and two compounds obtained from a differential scanning
      fluorimetry-based screen of a fragment library were determined by X-ray
      crystallography to resolutions of better than 2.0 A. The enzyme shows the typical
      alpha-helical fold of farnesyl pyrophosphate synthases. The substrate GPP binds
      in the S1 substrate site in an open conformation of the enzyme. In the enzyme
      ibandronate complex three inhibitor molecules are bound in the active site of the
      enzyme. One inhibitor molecule occupies the allylic substrate site (S1) of each
      subunit, as observed in complexes of nitrogen-containing bisphosphonate
      inhibitors of farnesyl synthases from other species. Two (in subunit A) and one
      (in subunit B) additional ibandronate molecules are bound in the active site. The
      structures of the fragment complexes show two molecules bound in a hydrophobic
      pocket adjacent to the active site. This allosteric pocket, which has previously
      only been described for FPPS from eukaryotic organisms, is thus also present in
      enzymes from pathogenic prokaryotes and might be utilized for the design of
      inhibitors of bacterial FPPS with a different chemical scaffold to the highly
      charged bisphosphonates, which are less likely to pass bacterial membranes. 

PMID- 25760622
TI  - Engineering more stable, selectable marker-free autoluminescent mycobacteria by
      one step.
AB  - In our previous study, we demonstrated that the use of the autoluminescent
      Mycobacterium tuberculosis as a reporter strain had the potential to drastically
      reduce the time, effort, animals and costs consumed in evaluation of the
      activities of drugs and vaccines in live mice. However, the strains were
      relatively unstable and lost reporter with time without selection. The kanamycin
      selection marker used wasn't the best choice as it provides resistance to amino
      glycosides which are an important class of second line drugs used in tuberculosis
      treatment. In addition, the marker could limit utility of the strains for
      screening of new potential drugs or evaluating drug combinations for tuberculosis
      treatment. Limited selection marker genes for mycobacterial genetic manipulation
      is a major drawback for such a marker-containing strain in many research fields.
      Therefore, selectable marker-free, more stable autoluminescent mycobacteria are
      highly needed. After trying several strategies, we created such mycobacterial
      strains successfully by using an integrative vector and removing both the
      resistance maker and integrase genes by Xer site-specific recombination in one
      step. The corresponding plasmid vectors developed in this study could be very
      convenient in constructing other selectable marker-free, more stable reporter
      mycobacteria with diverse applications. 

PMID- 25760623
TI  - Pre-implantation genetic screening and diagnosis: what doctors should know.

PMID- 25760624
TI  - [Prevalence of toxoplasmosis in pregnant women in two reference centers in a city
      in Northeast Brazil].
AB  - PURPOSE: To determine the prevalence of toxoplasmosis and to identify the main
      factors associated with seroreactivity in pregnant women cared for at two
      reference centers in a city in Northeast Brazil. METHODS: A cross-sectional study
      was conducted on 561 pregnant women at two high-risk prenatal reference centers
      in a city in Northeast Brazil. All women were interviewed using an
      epidemiological questionnaire and had their blood samples collected for the
      following serological tests: anti-Toxoplasma gondii IgG and IgM (ELISA), IgG
      avidity test, and polymerase chain reaction (PCR). Statistical analysis was
      carried out using SPSS version 18.0 for Windows, calculating odds ratio,
      confidence interval of 95% and with the level of significance set at 5%. RESULTS:
      Seroreactivity for toxoplasmosis was detected in 437 women (77.0%),
      susceptibility in 124 (22.1%) and active infection in 5 (0.9%). There was no
      significant association between seroreactivity for toxoplasmosis and age,
      location, income, education, availability of sewage, number of pregnancies or
      gestational age. The variables significantly associated (p<=0.05) with
      seroreactivity were multiparity (p=0.03) and living with stray dogs (p=0.01).
      CONCLUSIONS: This study identified high seroreactivity for toxoplasmosis among
      patients seen during prenatal care, as well as factors associated with
      seroreactivity. Appropriate guidelines about primary preventive measures should
      be emphasized and quarterly serological monitoring is recommended for pregnant
      women in this city and elsewhere in the Northeast of Brazil.

PMID- 25760625
TI  - Metabolism and gene polymorphisms of the folate pathway in Brazilian women with
      history of recurrent abortion.
AB  - PURPOSE: To investigate the association between polymorphisms in genes that
      encode enzymes involved in folate- and vitamin B12-dependent homocysteine
      metabolism and recurrent spontaneous abortion (RSA). METHODS: We investigated the
      C677T and A1298C polymorphisms of the methylenetetrahydrofalate reductase gene
      (MTHFR), the A2756G polymorphism of the methionine synthase gene (MS) and the
      844ins68 insertion of the cystathionine beta synthetase gene (CBS). The PCR
      technique followed by RFLP was used to assess the polymorphisms; the serum levels
      of homocysteine, vitamin B12 and folate were investigated by chemiluminescence.
      The EPI Info Software version 6.04 was used for statistical analysis. Parametric
      variables were compared by Student's t-test and nonparametric variables by the
      Wilcoxon rank sum test. RESULTS: The frequencies of gene polymorphisms in 89
      women with a history of idiopathic recurrent miscarriage and 150 controls were
      19.1 and 19.6% for the C677T, insertion, 20.8 and 26% for the A1298C insertion,
      14.2 and 21.9% for the A2756G insertion, and 16.4 and 18% for the 844ins68
      insertion, respectively. There were no significant differences between case and
      control groups in any of the gene polymorphisms investigated. However, the
      frequency of the 844ins68 insertion in the CBS gene was higher among women with a
      history of loss during the third trimester of pregnancy (p=0.003). Serum
      homocysteine, vitamin B12 and folate levels id not differ between the
      polymorphisms studied in the case and control groups. However, linear regression
      analysis showed a dependence of serum folate levels on the maintenance of tHcy
      levels. CONCLUSION: The investigated gene polymorphisms and serum homocysteine,
      vitamin B12 and folate levels were not associated with idiopathic recurrent
      miscarriage in the present study. Further investigations are needed in order to
      confirm the role of the CBS 844ins68 insertion in recurrent miscarriage.

PMID- 25760626
TI  - [Predictive factors for recurrence of ovarian endometrioma after laparoscopic
      excision].
AB  - PURPOSE: To analyze the factors that might influence the recurrence of ovarian
      endometriomas after laparoscopic excision. METHODS: A retrospective cohort study.
      We evaluated 129 patients who underwent laparoscopic excision of ovarian
      endometriomas from 2003 to 2012 and who were followed up for at least two years
      after surgery. Vaginal ultrasound was repeated to exclude persistent lesion and
      to identify recurrence. The Student's t-test was used to compare continuous
      variables and the chi2 or Fischer exact test (for values of less than five) was
      used to test homogeneity between proportions. A logistic regression model for
      multivariate proportional hazards was used to analyze predictors of long-term
      outcome. The level of significance was set at 5% in all analyses. RESULTS: The
      overall rate of ovarian endometrioma recurrence was 18.6%. Endometrioma diameter,
      surgical procedure techniques and demographic data such as age, presenting
      symptoms, body mass index, smoking and physical exercise habits were not
      associated with recurrence, whereas interruption of postoperative medical
      treatment was significantly correlated with a higher recurrence rate (OR 23.7;
      95%CI 5.26-107.05; p=0.001). CONCLUSION: Current oral contraceptive use appears
      to be associated with a dramatic reduction in the risk of recurrence of ovarian
      endometriotic cysts. Treatment interruption was associated with a higher
      recurrence rate of ovarian endometrioma after laparoscopic treatment.

PMID- 25760627
TI  - [Risk factors for urinary incontinence in elderly women practicing physical
      exercises].
AB  - PURPOSE: To analyze the risk factors for urinary incontinence (UI) in older women
      practicing physical exercises (PE). METHODS: A total of 152 older women with a
      mean age of 68.6+/-5.8 years who regularly practiced PE participated in the
      study. The presence of UI and gynecological, obstetric, clinical, behavioral,
      hereditary and anthropometric risk factors was determined identified. It was also
      applied the Domain 4 of the International Physical Activity Questionnaire (IPAQ)
      to determine the level of physical activity and body mass index and waist
      circumference were measured. Data were analyzed using descriptive and inferential
      statistics, with the level of significance set at 5%. RESULTS: The prevalence of
      UI in the sample was 32.2%. Among the factors evaluated, only the use of
      diuretics (OR=2.7; 95%CI 1.0-7.0) and a positive family history of urinary
      incontinence (OR=2.3; 95%CI 1.1-4.8) were associated with UI symptoms.
      CONCLUSION: The use of diuretics is considered to be a modifiable risk factor for
      UI, whereas a family history is not considered to be a modifiable risk factor.

PMID- 25760628
TI  - [Histological classification and quality of life in women with endometriosis].
AB  - PURPOSE: To assess the relationship between the histological classification and
      the quality of life of patients operated for endometriosis. METHODS: A cross
      sectional observational study, with assessment of 32 biopsies of the intestine,
      peritoneum and uterosacral ligament from 40 women with deep endometriosis. The
      quality of life (QOL) was determined by applying the SF-36 questionnaire pre
      operatively and at 6 and 12 months postoperatively. Biopsies were histologically
      classified into pure stromal (EP), glandular differentiated (GD), glandular
      undifferentiated (GI) and mixed (GM), remaining in the sample only GI and GM,
      which are related to eight domains of the SF-36. RESULTS: According to the
      histologic type, the following distribution was observed: peritoneum 63% GI and
      35% GM; intestine 19% GI and 24% GM; uterosacral ligament with 41% GI and 35% GM.
      Regarding the QOL and the histological classification, in the intestine only GM
      was associated with improvement of social and emotional aspects from 0 to 6
      months; the domains general health status (p=0.01) and social aspect (p=0.04)
      were significantly related to improvement of the QOL from 0 to 6 months, and the
      general health status tended to improve from 0 to 12 months. Regarding pain
      (p=0.06) and the emotional aspect (p=0.05), the QOL tended to improve from 0 to 6
      months and the vital capacity (p=0.1) improved from 0 to 6 months and from 0 to
      12 months. Regarding the emotional aspect, evolution of the two histological
      types was not favorable for improvement in MG from 0 to 6 months. No significant
      relationships between histologic type and QOL were evident in the uterosacral
      ligament samples. CONCLUSION: Improvement in the QOL of women undergoing
      laparoscopic surgery for deep endometriosis is associated with the histologic
      grade. The peritoneal biopsy of GI revealed improved QOL after surgery.

PMID- 25760629
TI  - [Comparison of two techniques for HPV genotyping in women with high-grade
      squamous intraepithelial lesion].
AB  - PURPOSE: The aim of this study was to compare the performance of two human
      papillomavirus (HPV) genotyping techniques, Linear Array and PapilloCheck, in
      women with high-grade squamous intraepithelial lesion (HSIL). METHODS: A total of
      88 women with cytological diagnosis of HSIL were recruited at 2 reference centers
      in cervical pathology in Salvador, Bahia, Brazil, from July 2006 to January 2009.
      After the cytological diagnosis of HSIL, cervix cells were collected to determine
      the HPV genotype and a biopsy was obtained under colposcopic vision for
      histopathological analysis. After the confirmation of CIN2+ by histopathology,
      HPV genotyping was performed on 41 women by the Linear Array and PapilloCheck
      methods. RESULTS: Both tests showed an overall concordance rate for HPV detection
      of 97.2% (35/36). Of the 36 valid samples, 35 (97.2%) were positive in both tests
      and 1 (2.8%) was discordant, with the Linear Array indicating the presence of
      multiple types. The most prevalent HPV genotypes detected by the Linear Array
      technique were HPV 16, HPV 56, HPV 35, HPV 45, and HPV 70; and those detected by
      the PapilloCheck technique were HPV 16, HPV 56, HPV 11, HPV 35, and HPV 42. A
      similar rate of infection with multiple HPV types was observed with the two tests
      (72.5% with the Linear Array and 75.0% with the PapilloCheck). CONCLUSIONS:
      Linear Array genotyping assay and PapilloCheck showed equivalent performance for
      the detection of oncogenic HPV types in women with HSIL, with PapilloCheck having
      the advantage of being a method that avoids subjectivity when reading the HPV
      genotypes.

PMID- 25760630
TI  - Muscle-specific E3 ubiquitin ligases are involved in muscle atrophy of cancer
      cachexia: an in vitro and in vivo study.
AB  - Muscle atrophy F-Box (MAFbx)/atrogin-1 and muscle ring-finger-1 (MuRF-1) have
      been identified as two muscle-specific E3 ubiquitin ligases that are highly
      expressed in skeletal muscle during muscle atrophy. However, the role of muscle
      specific E3 ubiquitin ligases during the process of muscle atrophy of cancer
      cachexia remains largely unknown. In the present study, we analyzed the
      expression of atrogin-1 and MuRF-1 in the skeletal muscle of patients with
      malignant and benign disease. The possible mechanisms were studied both in a
      colon 26-induced cancer cachexia mouse model and in tumor necrosis factor-alpha
      (TNF-alpha) induced atrophy C2C12 cells. Our results demonstrated that atrogin-1
      and MuRF-1 tended to be increased in the skeletal muscle of patients with
      malignant disease even before weight loss. Non-tumor body weights and
      gastrocnemius weights were significantly decreased while expression levels of
      ubiquitin proteasome pathway associated genes (atrogin-1, MuRF-1, ubiquitin and
      E2-14K) were upregulated in cancer cachexia mice. Significant myotube atrophy
      with atrogin-1 overexpression was observed in the C2C12 cells treated with TNF
      alpha. Meanwhile, knockdown of atrogin-1 by small interfering RNA (siRNA)
      protected C2C12 cells from the adverse effect of TNF-alpha. In conclusion, muscle
      specific E3 ubiquitin ligases were upregulated during cancer cachexia, and
      atrogin-1 may be a potential molecular target for treating muscle atrophy induced
      by cancer cachexia. 

PMID- 25760631
TI  - CD169-mediated trafficking of HIV to plasma membrane invaginations in dendritic
      cells attenuates efficacy of anti-gp120 broadly neutralizing antibodies.
AB  - Myeloid dendritic cells (DCs) can capture HIV-1 via the receptor CD169/Siglec-1
      that binds to the ganglioside, GM3, in the virus particle membrane. In turn, HIV
      1 particles captured by CD169, an I-type lectin, whose expression on DCs is
      enhanced upon maturation with LPS, are protected from degradation in CD169+ virus
      containing compartments (VCCs) and disseminated to CD4+ T cells, a mechanism of
      DC-mediated HIV-1 trans-infection. In this study, we describe the mechanism of
      VCC formation and its role in immune evasion mechanisms of HIV-1. We find HIV-1
      induced formation of VCCs is restricted to myeloid cells, and that the
      cytoplasmic tail of CD169 is dispensable for HIV-1 trafficking and retention
      within VCCs and subsequent trans-infection to CD4+ T cells. Interestingly,
      introduction of a di-aromatic endocytic motif in the cytoplasmic tail of CD169
      that results in endocytosis of HIV-1 particles, suppressed CD169-mediated HIV-1
      trans-infection. Furthermore, super-resolution microscopy revealed close
      association of CD169 and HIV-1 particles in surface-accessible but deep plasma
      membrane invaginations. Intriguingly, HIV-1 particles in deep VCCs were
      inefficiently accessed by anti-gp120 broadly neutralizing antibodies, VRC01 and
      NIH45-46 G54W, and thus were less susceptible to neutralization. Our study
      suggests that HIV-1 capture by CD169 can provide virus evasion from both innate
      (phagocytosis) and adaptive immune responses.

PMID- 25760633
TI  - Prospects and challenges of iron pyroelectrolysis in magnesium aluminosilicate
      melts near minimum liquidus temperature.
AB  - Although steel production by molten oxide electrolysis offers potential economic
      and environmental advantages over classic extractive metallurgy, its feasibility
      is far from being convincingly demonstrated, mainly due to inherent experimental
      difficulties exerted by harsh conditions and lack of knowledge regarding relevant
      mechanisms and physico-chemical processes in the melts. The present work was
      intended to demonstrate the concept of pyroelectrolysis at very high temperature
      near the minimum liquidus point of magnesium aluminosilicate, being conducted
      under electron-blocking conditions using yttria-stabilized zirconia cells, and to
      provide a new insight into electrochemistry behind this process. Significant
      current yields are possible for pyroelectrolysis performed in electron-blocking
      mode using a solid electrolyte membrane to separate the anode and the molten
      electrolyte. Parasitic electrochemical processes rise gradually as the
      concentration of iron oxide dissolved in the molten electrolytes is depleted,
      impairing faradaic efficiency. Reduction of silica to metallic silicon was
      identified as a significant contribution to those parasitic currents, among other
      plausible processes. Direct pyroelectrolysis without electron blocking was found
      much less plausible, due to major limitations on faradaic efficiency imposed by
      electronic leakage and insufficient ionic conductivity of the aluminosilicate
      melt. Ohmic losses may consume an excessive fraction of the applied voltage, thus
      failing to sustain the Nernst potential required for reduction to metallic iron.
      The results suggest the need for further optimization of the molten electrolyte
      composition to promote ionic conductivity and to suppress electronic transport
      contribution, possibly, by tuning the Al/Si ratio and altering the network
      forming/modifying behaviour of the iron cations. 

PMID- 25760632
TI  - Specific management of post-chikungunya rheumatic disorders: a retrospective
      study of 159 cases in Reunion Island from 2006-2012.
AB  - BACKGROUND: Since 2003, the tropical arthritogenic chikungunya (CHIK) virus has
      become an increasingly medical and economic burden in affected areas as it can
      often result in long-term disabilities. The clinical spectrum of post-CHIK
      (pCHIK) rheumatic disorders is wide. Evidence-based recommendations are needed to
      help physicians manage the treatment of afflicted patients. PATIENTS AND METHODS:
      We conducted a 6-year case series retrospective study in Reunion Island of
      patients referred to a rheumatologist due to continuous rheumatic or
      musculoskeletal pains that persisted following CHIK infection. These various
      disorders were documented in terms of their clinical and therapeutic courses.
      Post-CHIK de novo chronic inflammatory rheumatisms (CIRs) were identified
      according to validated criteria. RESULTS: We reviewed 159 patient medical files.
      Ninety-four patients (59%) who were free of any articular disorder prior to CHIK
      met the CIR criteria: rheumatoid arthritis (n=40), spondyloarthritis (n=33),
      undifferentiated polyarthritis (n=21). Bone lesions detectable by radiography
      occurred in half of the patients (median time: 3.5 years pCHIK). A positive
      therapeutic response was achieved in 54 out of the 72 patients (75%) who were
      treated with methotrexate (MTX). Twelve out of the 92 patients (13%) received
      immunomodulatory biologic agents due to failure of contra-indication of MTX
      treatment. Other patients mainly presented with mechanical shoulder or knee
      disorders, bilateral distal polyarthralgia that was frequently associated with
      oedema at the extremities and tunnel syndromes. These pCHIK musculoskeletal
      disorders (MSDs) were managed with pain-killers, local and/or general anti
      inflammatory drugs, and physiotherapy. CONCLUSION: Rheumatologists in Reunion
      Island managed CHIK rheumatic disorders in a pragmatic manner following the
      outbreak in 2006. This retrospective study describes the common mechanical and
      inflammatory pCHIK disorders. We provide a diagnostic and therapeutic algorithm
      to help physicians deal with chronic patients, and to limit both functional and
      economic impacts. The therapeutic indication of MTX in pCHIK CIR could be
      approved in future efficacy trials.

PMID- 25760634
TI  - Trust matters: A narrative literature review of the role of trust in health care
      systems in sub-Saharan Africa.
AB  - This article makes a contribution to the debate about health service utilisation
      and the role of trust in fostering demand for health services in sub-Saharan
      Africa. It is framed as a narrative literature review based on a thematic
      analysis of nine empirical, qualitative studies. For the purposes of this article
      trust is defined as a voluntary course of action, which involves the optimistic
      expectation that the trustee will do no harm to the trustor and is increasingly
      perceived as an important influence on health system functioning. The article
      looks at trust issues in interpersonal, intergroup and institutional situations.
      The findings of the review point to four elements that are important for trust to
      develop in health sector relationships: the sensitive use of discretionary power
      by health workers, perceived empathy by patients of the health workers, the
      quality of medical care and workplace collegiality. When trust works in health
      sector encounters, it reduces the social complexity and inherent uneven
      distribution of power between clients and providers. The article concludes that
      understanding and supporting trust processes between patients and providers, as
      well as between co-workers and managers, will improve health sector collaboration
      and stimulate demand for health care services. 

PMID- 25760635
TI  - Simulating irrational human behavior to prevent resource depletion.
AB  - In a situation with a limited common resource, cooperation between individuals
      sharing the resource is essential. However, people often act upon self-interest
      in irrational ways that threaten the long-term survival of the whole group. A
      lack of sustainable or environmentally responsible behavior is often observed. In
      this study, we examine how the maximization of benefits principle works in a
      wider social interactive context of personality preferences in order to gain a
      more realistic insight into the evolution of cooperation. We used time
      perspective (TP), a concept reflecting individual differences in orientation
      towards past, present, or future, and relevant for making sustainable choices. We
      developed a personality-driven agent-based model that explores the role of
      personality in the outcomes of social dilemmas and includes multiple facets of
      diversity: (1) The agents have different behavior strategies: individual
      differences derived by applying cluster analysis to survey data from 22 countries
      (N = 10,940) and resulting in 7 cross-cultural profiles of TP; (2) The non
      uniform distribution of the types of agents across countries; (3) The diverse
      interactions between the agents; and (4) diverse responses to those interactions
      in a well-mixed population. As one of the results, we introduced an index of
      overall cooperation for each of the 22 countries, which was validated against
      cultural, economic, and sustainability indicators (HDI, dimensions of national
      culture, and Environment Performance Index). It was associated with higher human
      development, higher individualism, lower power distance, and better environmental
      performance. The findings illustrate how individual differences in TP can be
      simulated to predict the ways people in different countries solve the personal
      vs. common gain dilemma in the global limited-resource situation. This
      interdisciplinary approach to social simulation can be adopted to explain the
      possible causes of global environmental issues and to predict their possible
      outcomes. 

PMID- 25760636
TI  - Sustained CD4 and CD8 lymphopenia after rituximab maintenance therapy following
      bendamustine and rituximab combination therapy for lymphoma.

PMID- 25760638
TI  - Utility of the immunoglobulin free light chain assay for plasma cell disorders
      2015.

PMID- 25760637
TI  - Carmustine, etoposide, cytarabine and melphalan versus a newly designed
      intravenous busulfan-based Busulfex, etoposide and melphalan conditioning regimen
      for autologous hematopoietic cell transplant: a retrospective matched-pair
      analysis in advanced Hodgkin and non-Hodgkin lymphomas.
AB  - Optimal conditioning remains a challenge in lymphomas. We designed a regimen
      consisting of Busulfex, etoposide and melphalan (BuEM). We retrospectively
      analyzed the outcome of patients conditioned with carmustine, etoposide,
      cytarabine and melphalan (BEAM) or BuEM in matched-pair analysis on a planned 2:1
      ratio. Eighty-seven patients treated with BEAM who fulfilled the matching
      criteria were randomly selected. Two-year progression-free survival/overall
      survival (PFS/OS) were 63.2%/76.7% for BEAM vs. 65.6%/79.8% for BuEM after 64.7
      and 42.7 months, respectively. Furthermore, marginally better PFS and OS were
      noted in Hodgkin lymphoma (HL) after BuEM. In multivariate analysis, PFS was
      superior in HL, chemosensitive disease and complete remission post-transplant.
      BEAM correlated with faster engraftment, reduced infections, less mucositis and
      liver toxicity, and BuEM with less need for blood cell and platelet transfusions
      and granulocyte colony-stimulating factor administration. In conclusion, BuEM was
      well tolerated and equally highly efficacious as BEAM for non-Hodgkin lymphoma
      and offered marginally significantly improved PFS and OS in HL with acceptable
      toxicity and zero mortality. 

PMID- 25760639
TI  - Advances in patents related to intrapocket technology for the management of
      periodontitis.
AB  - Increased prevalence of oral diseases such as gingivitis, periodontitis and
      dental caries has become major health issue worldwide. Such growing incidence of
      periodontitis has directly affected the development of drug delivery systems and
      growth of the market. Since the infections are limited to periodontal pockets or
      oral cavity, localized intrapocket drug delivery will be more beneficial than
      conventional systemic administration. Advances in intrapocket technology and
      innovations in the field of periodontal drug delivery led to increased patent
      applications. Newer trends like use of mucoadhesive polymers, in situ forming
      gels, viscosity modifiers, plasticizers etc which can enhance intrapocket
      retention of drugs have gained considerable attention among researchers and
      industrialists. Current market is flooded with products such as Periostat,
      Periochip((r)), Atridox((r)), Arestin((r)), Actisite((r)), Dentomycin((r)), and
      Elyzol((r)) and generics such as metronidazole, levofloxacin, tetracycline,
      doxycyline and minocycline for intrapocket delivery. There is a need of novel
      drugs and delivery systems with better efficacy profiles than the existing
      compounds. Inclusion of novel technologies like films, fibers, in situ forming
      implants, microparticles, nanoparticles, and liposomes as intrapocket drug
      delivery has great potential. Development of antibiotic free drug delivery such
      as antiseptics, host modulators, biofilms inhibitors and antibodies has promising
      role in the improvement of pathogenesis of periodontitis. Further, this review
      deals with various innovations in drug delivery and patents related to localized
      intrapocket administration of medicaments in the implications of periodontitis. 

PMID- 25760640
TI  - Immunologic Overlap of Helper T-Cell Subtypes 17 and 22 in Erythrodermic
      Psoriasis and Atopic Dermatitis.
AB  - IMPORTANCE: Psoriasis and atopic dermatitis (AD) are inflammatory diseases
      thought to be mediated by helper T-cell subtypes 1 and 2 (TH1 and TH2),
      respectively. Although psoriasis and AD show histopathologic differences during
      chronic disease, they are difficult to distinguish histologically during
      erythrodermic exacerbations. OBJECTIVE: To determine whether the immune phenotype
      of helper T cells can differentiate erythrodermic psoriasis and erythrodermic AD
      by studying skin biopsy specimens of patients with psoriasis and AD during
      erythrodermic and chronic disease phases. DESIGN, SETTING, AND PARTICIPANTS: We
      conducted a retrospective study using biopsy samples of psoriasis, AD, and
      erythroderma belonging to the surgical pathology files of the James Homer Wright
      Pathology Laboratories, Massachusetts General Hospital, and collected from
      January 1, 2004, through December 31, 2011. Samples were obtained from patients
      with chronic psoriasis (n = 20), chronic AD (n = 20), erythroderma subsequently
      diagnosed as psoriasis (n = 7), and erythroderma subsequently diagnosed as AD (n
      = 5). We evaluated immunohistochemical stains for CD3 and dual stains for CD4 and
      T-bet, GATA binding protein 3 (GATA3), signal transducer and activator of
      transcription 3 (STAT3), or basonuclin 2 (BNC2), which are transcription factors
      reported to be specific and mutually exclusive for TH1, TH2, TH17, and TH22
      cells, respectively. Two investigators independently counted CD3+ cells and dual
      labeled CD4+/T-bet+, CD4+/GATA3+, CD4+/STAT3+, and CD4+/BNC2+ cells in 5
      consecutive high-power fields. MAIN OUTCOMES AND MEASURES: We evaluated the
      percentage of TH1, TH2, TH17, and TH22 cells in CD3+ T cells and the TH1:TH2
      ratio in chronic psoriasis, chronic AD, erythrodermic psoriasis, and
      erythrodermic AD. RESULTS: We found a significant difference in the TH1:TH2 ratio
      between chronic psoriasis and chronic AD (0.26 and 0.09, respectively; P = .005).
      However, we detected no significant difference in the percentage of TH1 (6.5% and
      4.8%), TH2 (55.2% and 64.6%), TH17 (14.7% and 30.4%), and TH22 (3.8% and 3.3%)
      cells of CD3+ T cells or in the TH1:TH2 ratio (0.16 and 0.07) within biopsy
      specimens from patients with erythrodermic psoriasis and AD, respectively.
      CONCLUSIONS AND RELEVANCE: This study confirms the TH1- and TH2-skewed phenotype
      of chronic psoriasis and chronic AD, respectively. However, the immune phenotype,
      as determined by immunohistochemical analysis, cannot discriminate between these
      inflammatory diseases in the erythrodermic phase. These findings advance our
      understanding of the pathophysiological characteristics of erythroderma,
      psoriasis, and AD and may influence therapeutic decisions.

PMID- 25760641
TI  - Novel features of neurodegeneration in the inner retina of early diabetic rats.
AB  - The literature indicates that in diabetes retinal dysfunctions related to neural
      retinal alterations exist prior to clinically detectable vasculopathy. In a
      previous report, a detailed description about the alteration of the outer retina
      was given, where diabetic degeneration preceded apoptotic loss of cells (Enzsoly
      et al., 2014). Here, we investigated the histopathology of the inner retina in
      early diabetes using the same specimens. We examined rat retinas with
      immunohistochemistry and Western blotting, 12 weeks after streptozotocin
      induction of diabetes. Glial reactivity was observed in all diabetic retinal
      specimens; however, it was not detectable all over the retina, but appeared in
      randomly arranged patches, with little or no glia activation in between.
      Similarly, immunoreactivity of parvalbumin (staining mostly AII amacrine cells)
      was also decreased only in some regions. We propose that these focal changes
      appear prior to affecting the whole retina and overt loss of cells. In contrast
      to these, most other markers used (calretinin, recoverin, tyrosin hydroxylase
      anti-Brn-3a and also calbindin in the optic part of the retina) did not show any
      major alterations in the intensity of immunoreactivity or in the number of
      stained elements. Interestingly, under diabetic conditions, the labeling pattern
      of PKC-alpha and calbindin in the ciliary retina showed a clear resemblance to
      the pattern described during development. This observation is in line with our
      previous study, reporting an increase in the number of dual cones, coexpressing
      two photopigments, which is another common feature with developing retinas. These
      data may indicate a previously uninvestigated regenerative capacity in diabetic
      retina. 

PMID- 25760642
TI  - Copper and nickel partitioning with nanoscale goethite under variable aquatic
      conditions.
AB  - Metal contaminated sediments can be toxic to aquatic organisms and are common in
      human-dominated ecosystems, which results in metals being a leading cause of
      ecosystem impairment. Bioavailability of metals is influenced by their affinity
      for dissolved and solid-phase ligands, including iron (Fe) oxyhydroxides, which
      have been hypothesized to reduce metal toxicity in sediments. The authors
      examined the adsorption kinetics of copper (Cu) and nickel (Ni) with goethite
      (alpha-FeOOH) and characterized the influences of solute metal concentration, pH,
      ionic strength, and humate concentration on steady-state partitioning of the
      metals with goethite under conditions representative of natural aquatic
      environments. Copper and Ni readily adsorbed to goethite, and steady-state
      partitioning was achieved within 2 h. Although ionic strength had no effect on
      metal partitioning, adsorption of Cu and Ni to goethite was enhanced by alkaline
      pH and reduced by competition with humate. Because distribution coefficient (KD )
      values for Cu and Ni from the present study are comparable to values measured in
      natural systems, the authors hypothesize that goethite may contribute
      significantly to the adsorption of both Ni and Cu to particles in the
      environment. The authors suggest that incorporating binding by Fe oxides in metal
      bioavailability models should be a priority for improving risk assessment of
      metal-contaminated oxic sediments.

PMID- 25760643
TI  - A three-dimensional complex with a one-dimensional cobalt-hydroxyl chain based on
      planar nonanuclear clusters showing spin-canted antiferromagnetism.
AB  - A new three-dimensional magnetic network, [Co9(OH)6(C42H24O18P3N3)2(H2O)8] (1),
      has been successfully prepared by utilizing the flexible hexacarboxylate ligand
      derived from cyclotriphosphazene, which had been characterized by single-crystal
      X-ray diffraction and magnetic measurement. This compound consists of one
      dimensional (1D) cobalt-hydroxyl chains based on planar nonanuclear clusters,
      which are located in the b-c plane to form the nearly two-dimensional cobalt
      layer. Magnetic measurements reveal that 1 shows spin-canted antiferromagnetism
      with spin-glass behavior. These results suggest that reasonable design and choice
      of large carboxylate ligand based on a specific scaffold could be effective for
      the construction of magnetic materials based on a novel 1D magnetic chain. 

PMID- 25760644
TI  - Favorable survival time provided with radioembolization in hepatocellular
      carcinoma patients with and without portal vein thrombosis.
AB  - PURPOSE: Although some algorithms are defined for the treatment of advanced
      hepatocellular carcinoma (HCC), the expected survival cannot be prolonged as it
      is intended. Treatment options for this group of patients are limited.
      Radioembolization with yttrium-90 (Y-90) microspheres is a new treatment
      modality, which has also been used in advanced HCC patients. In this study, the
      authors aimed to assess the efficiency of radioembolization with Y-90
      microspheres and evaluate prognostic factors that influence the survival in HCC
      patients. PATIENTS AND METHODS: The authors retrospectively evaluated data of 29
      HCC patients who had radioembolization with Y-90 resin or glass microspheres
      between May 2009 and January 2014. Patient survival was evaluated by using the
      Kaplan-Meier method. Subgroup comparisons in terms of age, sex, prior treatment
      status before radioembolization, tumor burden, time between HCC diagnosis and
      radioembolization, alpha fetoprotein (AFP) level before radioembolization,
      presence of portal vein thrombosis (PVT), hepatopulmonary shunt ratio,
      extrahepatic disease burden, multifocality, bilaterality, Eastern Cooperative
      Oncology Group (ECOG), Child-Pugh, and Barcelona Clinic Liver Cancer (BCLC)
      status were performed to evaluate prognostic factors that affected survival.
      RESULTS: There were 29 HCC patients (mean age: 59.9+/-12 years) in the patient
      group. Grade <=1 and 2 ECOG performance status was present in 19 and 10 patients,
      respectively. Twenty-six patients were classified as Child A and 3 patients as
      Child B. According to the BCLC staging system, 18 patients were in stage B and 11
      patients were in stage C. PVT was diagnosed in 12 patients. The median follow-up
      was 15 months. The median overall survival was 17+/-2.5 months. BCLC disease
      stage was a significant prognostic variable associated with survival, but other
      parameters, even the presence of PVT, were found to be not significantly
      affecting survival. CONCLUSION: Radioembolization provides favorable survival
      time in advanced HCC patients. Even patients who are not eligible for
      transarterial chemoembolization due to PVT can have radioembolization without a
      decrease in the median survival time.

PMID- 25760645
TI  - Physicians' attitudes toward medical screening in a dental setting.
AB  - OBJECTIVES: We assessed primary care physicians' attitudes toward medical
      screening in a dental setting. METHODS: A 5-point Likert scale (1 = very
      important/willing, 5 = very unimportant/unwilling) survey was mailed to a
      nationwide sample of primary care physicians in the United States. Descriptive
      statistics were used for all questions, and the Friedman nonparametric analysis
      of variance was used for multipart questions. RESULTS: Of 1,508 respondents, the
      majority felt it was valuable for dentists to conduct screening for
      cardiovascular disease (61 percent), hypertension (77 percent), diabetes mellitus
      (71 percent), and HIV infection (64 percent). Respondents were willing to discuss
      results with the dentist (76 percent), accept patient referrals (89 percent), and
      felt it was unimportant that the medical referral came from a dentist rather than
      a physician (52 percent). The most important consideration was patient
      willingness (mean rank 2.55), and the least important was duplication of roles
      (mean rank 3.52). Level of dentist's training was significantly (P < 0.05) more
      important than duplication of roles and reimbursement (mean ranks 2.84, 3.52, and
      3.14, respectively), and significantly less important than patient willingness
      (mean rank 2.55). CONCLUSIONS: Primary care physicians considered chairside
      medical screening in a dental setting to be valuable and worthwhile.

PMID- 25760647
TI  - The International Heart Transplant Survival Algorithm (IHTSA): a new model to
      improve organ sharing and survival.
AB  - BACKGROUND: Heart transplantation is life saving for patients with end-stage
      heart disease. However, a number of factors influence how well recipients and
      donor organs tolerate this procedure. The main objective of this study was to
      develop and validate a flexible risk model for prediction of survival after heart
      transplantation using the largest transplant registry in the world. METHODS AND
      FINDINGS: We developed a flexible, non-linear artificial neural networks model
      (IHTSA) and classification and regression tree to comprehensively evaluate the
      impact of recipient-donor variables on survival over time. We analyzed 56,625
      heart-transplanted adult patients, corresponding to 294,719 patient-years. We
      compared the discrimination power with three existing scoring models, donor risk
      index (DRI), risk-stratification score (RSS) and index for mortality prediction
      after cardiac transplantation (IMPACT). The accuracy of the model was excellent
      (C-index 0.600 [95% CI: 0.595-0.604]) with predicted versus actual 1-year, 5-year
      and 10-year survival rates of 83.7% versus 82.6%, 71.4%-70.8%, and 54.8%-54.3% in
      the derivation cohort; 83.7% versus 82.8%, 71.5%-71.1%, and 54.9%-53.8% in the
      internal validation cohort; and 84.5% versus 84.4%, 72.9%-75.6%, and 57.5%-57.5%
      in the external validation cohort. The IHTSA model showed superior or similar
      discrimination in all of the cohorts. The receiver operating characteristic area
      under the curve to predict one-year mortality was for the IHTSA: 0.650 (95% CI:
      0.640-0.655), DRI 0.56 (95% CI: 0.56-0.57), RSS 0.61 (95% CI: 0.60-0.61), and
      IMPACT 0.61 (0.61-0.62), respectively. The decision-tree showed that recipients
      matched to a donor younger than 38 years had additional expected median survival
      time of 2.8 years. Furthermore, the number of suitable donors could be increased
      by up to 22%. CONCLUSIONS: We show that the IHTSA model can be used to predict
      both short-term and long-term mortality with high accuracy globally. The model
      also estimates the expected benefit to the individual patient.

PMID- 25760648
TI  - Evidence for Neandertal jewelry: modified white-tailed eagle claws at Krapina.
AB  - We describe eight, mostly complete white-tailed eagle (Haliaetus [Haliaeetus]
      albicilla) talons from the Krapina Neandertal site in present-day Croatia, dating
      to approximately 130 kyrs ago. Four talons bear multiple, edge-smoothed cut
      marks; eight show polishing facets and/or abrasion. Three of the largest talons
      have small notches at roughly the same place along the plantar surface,
      interrupting the proximal margin of the talon blade. These features suggest they
      were part of a jewelry assemblage, --- the manipulations a consequence of
      mounting the talons in a necklace or bracelet. An associated phalanx articulates
      with one of the talons and has numerous cut marks, some of which are smoothed.
      These white-tailed eagle bones, discovered more than 100 years ago, all derive
      from a single level at Krapina and represent more talons than found in the entire
      European Mousterian period. Presence of eight talons indicates that the Krapina
      Neandertals acquired and curated eagle talons for some kind of symbolic purpose.
      Some have argued that Neandertals lacked symbolic ability or copied this behavior
      from modern humans. These remains clearly show that the Krapina Neandertals made
      jewelry well before the appearance of modern humans in Europe, extending ornament
      production and symbolic activity early into the European Mousterian. 

PMID- 25760650
TI  - Serum pentraxin 3 is a novel marker in Crohn's disease.
AB  - In Crohn's disease (CD), clinical symptoms correspond poorly to inflammatory
      disease activity. Biomarkers, which reflect the level of intestinal inflammation
      are considered to enable effective monitoring of disease activity. The present
      study evaluated the role of serum pentraxin 3 (PTX3) as a marker of disease
      activity in patients with CD. Serum PTX3 levels were determined using an enzyme
      linked immunosorbent assay in patients with CD (n=240), ulcerative colitis (UC;
      n=240) and healthy controls (HC; n=80). The expression levels of PTX3 were also
      evaluated in 35 fresh colonic tissue samples by western blot analysis. The
      association between levels of serum PTX3 with disease activity and its diagnostic
      role were analyzed. The levels of serum PTX3 were significantly increased in
      patients with active CD compared with patients in remission (UC and HC; P<0.01).
      A significant increase in the expression levels of PTX3 was identified at a
      protein level in inflamed colonic tissues compared with uninflamed colonic
      tissues. The levels of serum PTX3 were also positively correlated with disease
      activity in CD. These results indicated that serum and colonic expression of PTX3
      were upregulated in patients with active CD, suggesting serum PTX3 is superior to
      CRP in predicting CD activity.

PMID- 25760651
TI  - Active and passive problem solving: moderating role in the relation between
      depressive symptoms and future suicidal ideation varies by suicide attempt
      history.
AB  - OBJECTIVE: Research suggests that being unable to generate solutions to problems
      in times of distress may contribute to suicidal thoughts and behavior, and that
      depression is associated with problem-solving deficits. This study examined
      active and passive problem solving as moderators of the association between
      depressive symptoms and future suicidal ideation among suicide attempters and
      nonattempters. METHOD: Young adults (n = 324, 73% female, mean age = 19, standard
      deviation = 2.22) with (n = 78) and without (n = 246) a suicide attempt history
      completed a problem-solving task, self-report measures of hopelessness,
      depression, and suicidal ideation at baseline, and a self-report measure of
      suicidal ideation at 6-month follow-up. RESULTS: Passive problem solving was
      higher among suicide attempters but did not moderate the association between
      depressive symptoms and future suicidal ideation. Among attempters, active
      problem solving buffered against depressive symptoms in predicting future
      suicidal ideation. CONCLUSIONS: Suicide prevention should foster active problem
      solving, especially among suicide attempters.

PMID- 25760649
TI  - A millifluidic study of cell-to-cell heterogeneity in growth-rate and cell
      division capability in populations of isogenic cells of Chlamydomonas
      reinhardtii.
AB  - To address possible cell-to-cell heterogeneity in growth dynamics of isogenic
      cell populations of Chlamydomonas reinhardtii, we developed a millifluidic drop
      based device that not only allows the analysis of populations grown from single
      cells over periods of a week, but is also able to sort and collect drops of
      interest, containing viable and healthy cells, which can be used for further
      experimentation. In this study, we used isogenic algal cells that were first
      synchronized in mixotrophic growth conditions. We show that these synchronized
      cells, when placed in droplets and kept in mixotrophic growth conditions, exhibit
      mostly homogeneous growth statistics, but with two distinct subpopulations: a
      major population with a short doubling-time (fast-growers) and a significant
      subpopulation of slowly dividing cells (slow-growers). These observations suggest
      that algal cells from an isogenic population may be present in either of two
      states, a state of restricted division and a state of active division. When
      isogenic cells were allowed to propagate for about 1000 generations on solid agar
      plates, they displayed an increased heterogeneity in their growth dynamics.
      Although we could still identify the original populations of slow- and fast
      growers, drops inoculated with a single progenitor cell now displayed a wider
      diversity of doubling-times. Moreover, populations dividing with the same growth
      rate often reached different cell numbers in stationary phase, suggesting that
      the progenitor cells differed in the number of cell divisions they could
      undertake. We discuss possible explanations for these cell-to-cell
      heterogeneities in growth dynamics, such as mutations, differential aging or
      stochastic variations in metabolites and macromolecules yielding molecular
      switches, in the light of single-cell heterogeneities that have been reported
      among isogenic populations of other eu- and prokaryotes. 

PMID- 25760652
TI  - Label Design Affects Medication Safety in an Operating Room Crisis: A Controlled
      Simulation Study.
AB  - OBJECTIVE: Several factors contribute to medication errors in clinical practice
      settings, including the design of medication labels. The objective of this study
      was to quantify the impact of label design on medication safety in a realistic,
      high-stress clinical situation. METHODS: Ninety-six anesthesia trainee
      participants were randomly assigned to either the redesigned or the current label
      condition. Participants were blinded to the study's focus on medication label
      design and their assigned label condition. Each participant was the sole
      anesthesia provider in a simulated operating room scenario involving an
      unexpected vascular injury. The surgeon asked the participant to administer
      hetastarch to the simulated patient because of hemodynamic instability. The fluid
      drawer of the anesthesia cart contained three 500-ml intravenous bags of
      hetastarch and one 500-ml intravenous bag of lidocaine. We hypothesized that
      redesigned labels would help participants correctly select hetastarch from the
      cart. If the participants incorrectly selected lidocaine from the cart, we
      hypothesized that the redesigned labels would help participants detect the
      lidocaine before administration. RESULTS: The percentage of participants who
      correctly selected hetastarch from the cart was significantly higher for the
      redesigned labels than the current labels (63% versus 40%; odds ratio, 2.61 [95%
      confidence interval, 1.1-6.1]; P = 0.03). Of the participants who incorrectly
      selected lidocaine from the cart, the percentage who detected the lidocaine
      before administration did not differ by label condition. CONCLUSIONS: The
      redesigned labels helped participants correctly select hetastarch from the cart,
      thus preventing some potentially catastrophic medication errors from reaching the
      simulated patient.

PMID- 25760653
TI  - A reusable microRNA sensor based on the electrocatalytic property of heteroduplex
      templated copper nanoclusters.
AB  - DNA-RNA heteroduplexes have been used as templates for copper nanocluster (CuNC)
      formation for the first time. Taking advantage of the electrocatalysis of CuNCs,
      quantitation of miRNA can thus be accomplished. More importantly, by simply
      operating several rounds of CuNC formation, repeated detection of miRNA has
      further been realized, which is rare in miRNA biosensors. 

PMID- 25760654
TI  - EPSPS Gene Amplification in Glyphosate-Resistant Italian Ryegrass (Lolium perenne
      ssp. multiflorum) Populations from Arkansas (United States).
AB  - Glyphosate-resistant Italian ryegrass was detected in Arkansas (United States) in
      2007. In 2014, 45 populations were confirmed resistant in eight counties across
      the state. The level of resistance and resistance mechanisms in six populations
      were studied to assess the severity of the problem and identify alternative
      management approaches. Dose-response bioassays, glyphosate absorption and
      translocation experiments, herbicide target (EPSPS) gene sequence analysis, and
      gene amplification assays were conducted. The dose causing 50% growth reduction
      (GR50) was 7-19 times higher for the resistant population than for the
      susceptible standard. Uptake and translocation of (14)C-glyphosate were similar
      in resistant and susceptible plants, and no mutation in the EPSPS gene known to
      be associated with resistance to glyphosate was detected. Resistant plants
      contained from 11- to >100-fold more copies of the EPSPS gene than the
      susceptible plants, whereas the susceptible plants had only one copy of EPSPS.
      Plants surviving the recommended dose of glyphosate contained at least 10 copies.
      The EPSPS copy number was positively related to glyphosate resistance level (r =
      80). Therefore, resistance to glyphosate in these populations is due to
      multiplication of the target site. Resistance mechanisms could be location
      specific. Suppressing the mechanism for gene amplification may overcome
      resistance. 

PMID- 25760655
TI  - Noninvasive photoacoustic microscopy of methemoglobin in vivo.
AB  - Due to the various causes of methemoglobinemia and its potential to be confused
      with other diseases, in vivo measurements of methemoglobin have significant
      applications in the clinic. Using photoacoustic microscopy (PAM), we quantified
      the average and the distributed percentage of methemoglobin both in vitro and in
      vivo. Based on the absorption spectra of methemoglobin, oxyhemoglobin, and
      deoxyhemoglobin, three wavelengths were chosen to differentiate methemoglobin
      from the others. The methemoglobin concentrations calculated from the
      photoacoustic signals agreed well with the preset concentrations. Then we imaged
      the methemoglobin percentage in microtubes that mimicked blood vessels. Average
      percentages calculated for five samples with different methemoglobin
      concentrations also agreed well with the preset values. Finally, we demonstrated
      the ability of PAM to detect methemoglobin in vivo in a mouse ear. Our results
      show that PAM can quantitatively image methemoglobin distribution in vivo.

PMID- 25760656
TI  - Experimental infection of pregnant rabbits with hepatitis E virus demonstrating
      high mortality and vertical transmission.
AB  - A high mortality rate of approximately 20% in pregnant women with hepatitis E has
      been reported in previous studies. However, other studies showed no difference
      between pregnant and nonpregnant women in the severity of hepatitis E. To
      determine the effects of HEV infection on pregnancy, we successfully established
      HEV infection in six pregnant rabbits (PR) and six nonpregnant rabbits (NPR) with
      a rabbit HEV isolate, taking three PR and one NPR without HEV infection as
      controls. Tests for HEV RNA by RT-PCR, anti-HEV antibodies by ELISA and HEV
      antigen via immunohistochemistry and histopathology were carried out. Two of six
      infected PR miscarried and three of the remaining four PR died which may be
      attributed to severe liver necrosis caused by HEV infection. Moreover, vertical
      transmission was found to be associated with the replication of HEV in placenta,
      indicated by the presence of HEV RNA and antigen in placenta from the infected
      PR. Our findings strongly suggest that HEV infection could lead to adverse
      outcomes in pregnancy and vertical transmission, suggesting the necessity for
      pregnant women at risk of HEV infection to be vaccinated. 

PMID- 25760657
TI  - Investigating polymorphisms in membrane-associated transporter protein SLC45A2,
      using sucrose transporters as a model.
AB  - Solute carrier family 45 member 2 encodes the melanosomal membrane protein,
      membrane-associated transporter protein (MATP), of unknown function, that is
      required for normal melanin synthesis. The present study analyzed the effects of
      two human MATP mutations, D93N, which causes oculocutaneous albinism 4 (OCA4),
      and L374F, which is correlated with light pigmentation in European populations.
      Corresponding mutations were produced in the related and well-characterized
      sucrose transporter from rice, OsSUT1, and transport activity was measured by
      heterologous expression in Xenopus laevis oocytes, in addition to 14C-sucrose
      uptake in yeast. The mutation corresponding to D93N resulted in a complete loss
      of transport activity. The mutation corresponding to L374F resulted in a 90%
      decrease in transport activity, although the substrate affinity was unaffected.
      The results indicated that the D93N mutation causes OCA4 as a result of loss of
      MATP transport activity, and that the F374 allele confers significantly lower
      transport activity than L374.

PMID- 25760658
TI  - Selective oxidation of veratryl alcohol with composites of Au nanoparticles and
      graphene quantum dots as catalysts.
AB  - Veratryl alcohol can be oxidized to veratryl aldehyde or veratric acid with
      excellent selectivity and efficient conversion under acidic and alkaline
      conditions using Au nanoparticles and graphene quantum dot composites (Au/GQDs)
      as catalysts. 

PMID- 25760659
TI  - Stress disorders following prolonged critical illness in survivors of severe
      sepsis.
AB  - OBJECTIVES: To examine the frequency of acute stress disorder and posttraumatic
      stress disorder in chronically critically ill patients with a specific focus on
      severe sepsis, to classify different courses of stress disorders from 4 weeks to
      6 months after transfer from acute care hospital to postacute rehabilitation, and
      to identify patients at risk by examining the relationship between clinical,
      demographic, and psychological variables and stress disorder symptoms. DESIGN:
      Prospective longitudinal cohort study, three assessment times within 4 weeks, 3
      months, and 6 months after transfer to postacute rehabilitation. SETTING:
      Patients were consecutively enrolled in a large rehabilitation hospital (Clinic
      Bavaria, Kreischa, Germany) admitted for ventilator weaning from acute care
      hospitals. PATIENTS: We included 90 patients with admission diagnosis critical
      illness polyneuropathy or critical illness myopathy with or without severe
      sepsis, age between 18 and 70 years with a length of ICU stay greater than 5
      days. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Acute stress disorder
      and posttraumatic stress disorder were diagnosed according to the Diagnostic and
      Statistical Manual of Mental Disorders, 4th Edition, criteria by a trained and
      experienced clinical psychologist using a semistructured clinical interview for
      Diagnostic and Statistical Manual of Mental Disorders. We further administered
      the Acute Stress Disorder Scale and the Posttraumatic Symptom Scale-10 to assess
      symptoms of acute stress disorder and posttraumatic stress disorder. Three
      percent of the patients had an acute stress disorder diagnosis 4 weeks after
      transfer to postacute rehabilitation. Posttraumatic stress disorder was found in
      7% of the patients at 3-month follow-up and in 12% after 6 months, respectively.
      Eighteen percent of the patients showed a delayed onset of posttraumatic stress
      disorder. Sepsis turned out to be a significant predictor of posttraumatic stress
      disorder symptoms at 3-month follow-up. CONCLUSIONS: A regular screening of post
      ICU patients after discharge from hospital should be an integral part of
      aftercare management. The underlying mechanisms of severe sepsis in the
      development of posttraumatic stress disorder need further examination.

PMID- 25760660
TI  - Hospitals with the highest intensive care utilization provide lower quality
      pneumonia care to the elderly.
AB  - OBJECTIVE: Quality of care for patients admitted with pneumonia varies across
      hospitals, but causes of this variation are poorly understood. Whether hospitals
      with high ICU utilization for patients with pneumonia provide better quality care
      is unknown. We sought to investigate the relationship between a hospital's ICU
      admission rate for elderly patients with pneumonia and the quality of care it
      provided to patients with pneumonia. DESIGN: Retrospective cohort study. SETTING:
      Two thousand eight hundred twelve U.S. hospitals. PATIENTS: Elderly (age>=65
      years) fee-for-service Medicare beneficiaries with either a (1) principal
      diagnosis of pneumonia or (2) principal diagnosis of sepsis or respiratory
      failure and secondary diagnosis of pneumonia in 2008. INTERVENTIONS: None.
      MEASUREMENTS AND MAIN RESULTS: We grouped hospitals into quintiles based on ICU
      admission rates for pneumonia. We compared rates of failure to deliver pneumonia
      processes of care (calculated as 100-adherence rate), 30-day mortality, hospital
      readmissions, and Medicare spending across hospital quintile. After controlling
      for other hospital characteristics, hospitals in the highest quintile more often
      failed to deliver pneumonia process measures, including appropriate initial
      antibiotics (13.0% vs 10.7%; p<0.001), and pneumococcal vaccination (15.0% vs
      13.3%; p=0.03) compared with hospitals in quintiles 1-4. Hospitals in the highest
      quintile of ICU admission rate for pneumonia also had higher 30-day mortality, 30
      day hospital readmission rates, and hospital spending per patient than other
      hospitals. CONCLUSIONS: Quality of care was lower among hospitals with the
      highest rates of ICU admission for elderly patients with pneumonia; such
      hospitals were less likely to deliver pneumonia processes of care and had worse
      outcomes for patients with pneumonia. High pneumonia-specific ICU admission rates
      for elderly patients identify a group of hospitals that may deliver inefficient
      and poor-quality pneumonia care and may benefit from interventions to improve
      care delivery.

PMID- 25760661
TI  - Putting the puzzle pieces together.

PMID- 25760662
TI  - Medication review and transitions of care: a case report of a decade-old
      medication error.
AB  - A 69-year-old Caucasian male with a 25-year history of paranoid schizophrenia was
      brought to the emergency department because of violence toward the staff in his
      nursing facility. He was diagnosed with a urinary tract infection and was
      admitted to the behavioral health unit for medication stabilization. History
      included a five-year state psychiatric hospital admission and nursing facility
      placement. Because of poor cognitive function, the patient was unable to
      corroborate medication history, so the pharmacy student on rotation performed an
      in-depth chart review. The review revealed a transcription error in 2003 deleting
      amantadine 100 mg twice daily and adding amiodarone 100 mg twice daily.
      Subsequent hospitalization resulted in another transcription error increasing the
      amiodarone to 200 mg twice daily. All electrocardiograms conducted were negative
      for atrial fibrillation. Once detected, the consulted cardiologist discontinued
      the amiodarone, and the primary care provider was notified via letter and
      discharge papers. An admission four months later revealed that the nursing
      facility restarted the amiodarone. Amiodarone was discontinued and the facility
      was again notified. This case reviews how a 10-year-old medication error went
      undetected in the electronic medical records through numerous medication
      reconciliations, but was uncovered when a single comprehensive medication review
      was conducted. 

PMID- 25760663
TI  - The link between non-ergot-derived dopamine agonists and heart failure: how
      strong is it?
AB  - Dopamine agonists are commonly used as initial monotherapy and adjunct treatment
      for Parkinson's disease. However, the Food and Drug Administration recently
      linked pramipexole use with an increased risk of heart failure (HF). Several case
      control studies demonstrate a possible increased risk of the development of HF in
      patients taking non-ergot-derived dopamine agonists compared with patients not
      taking dopamine agonists. In patients taking non-ergot-derived dopamine agonists,
      the studies associated the risk of increased HF with pramipexole. These studies
      did not find a possible increased risk with ropinirole, but to date no
      randomized, controlled trials have been conducted to directly compare ropinirole
      with pramipexole and the risk of HF. The mechanism by which HF occurs is unknown,
      but the development of edema after dopamine agonist use could increase the risk
      of HF. If patients with a history of cardiovascular disease or edema are
      prescribed pramipexole, additional monitoring for HF signs and symptoms is
      recommended. 

PMID- 25760664
TI  - Pharmacist consultations: simplifying daily drug regimens and providing education
      on fall risk for older adults.
AB  - OBJECTIVE: To evaluate whether a medication review by a pharmacist in the
      community can simplify an older adult's daily drug regimen and improve awareness
      of medication-related fall risk. DESIGN: Pre- and posttest with follow-up design.
      SETTING: Senior centers, senior housing facilities, and community centers in
      Massachusetts. PARTICIPANTS: Older adults who attended a pharmacy outreach
      program at a community center. INTERVENTIONS: Participants engaged in a one-time,
      face-to-face, medication therapy management (MTM) session. The pharmacists made
      recommendations to simplify daily drug regimens for best therapeutic results. The
      participants were educated regarding the influence that medications may have on
      fall risk. RESULTS: For the 75 participants, daily dose regimens were
      significantly reduced. From the presurvey to the follow-up surveys, there was a
      significant increase of participants taking medication three times or fewer per
      day (73% to 85%) versus those participants taking medications more than three
      times per day (P = 0.041). Through MTM consultations, participants' awareness
      that medications may be a contributing factor to fall risk was increased from 28%
      in the presurvey to 56% in the postsurvey (P = 0.0018). CONCLUSION: A pharmacist
      consultation can simplify the daily drug regimen. Furthermore, consultant
      pharmacists can educate patients regarding the risk that medications may have on
      falls.

PMID- 25760665
TI  - Perceptions of care among high-risk geriatric patients, families, and caregivers
      in a patient-centered medical home.
AB  - OBJECTIVE: A survey was conducted by the pharmacy team to identify improvement
      areas in the delivery of care in high-risk patients at a patient-centered medical
      home (PCMH) at the University of Pittsburgh Medical Center (UPMC). DESIGN: This
      survey was a quality improvement project. SETTING: The survey was conducted at
      UPMC Senior Care, a level-three accredited PCMH. PATIENTS: The survey was
      conducted in a sample of preidentified high-risk patients. INTERVENTIONS:
      Pharmacy performed a survey, analyzed responses for common themes, and conducted
      follow-up phone calls to determine the degree of goal-achievement and efficacy of
      educational materials provided during the initial survey. MAIN OUTCOME MEASURE:
      The primary goal for conducting the survey was to identify needed areas for
      improvement in three specific domains, namely, medication decisions,
      communication with providers, and goals of care. RESULTS: Medication reviews were
      provided for 23 of 24 surveyed, leading to medication discrepancy resolution in
      58%. Almost 80% of the respondents were satisfied with the team's communication.
      More than 85% of respondents verbalized the goals they wanted to achieve in three
      months. The follow-up phone calls were conducted in 20 of those initially
      surveyed. Only 5 patients did not meet their goals. The following improvement
      areas were identified: need to provide medication lists and correct medication
      inaccuracies, need for medication review, patient goals documentation, and
      patient education and the appropriate medium of education. CONCLUSION: Future
      appointments for high-risk patients at the PCMH should include the pharmacist.
      The team should focus education on families/caregivers and utilize alternate
      patient education methods.

PMID- 25760666
TI  - Pharmacists' experiences with a telephonic medication therapy management program
      for home health care patients.
AB  - OBJECTIVE: This study was designed to better understand perceived barriers and
      facilitators to providing medication therapy management (MTM) services by
      pharmacists who recently provided telephonic MTM services to home health care
      patients. These services were provided as part of a randomized, controlled trial
      (RCT) to develop suggested quality improvement strategies for future service
      design. DESIGN: This was a qualitative study. A semi-structured individual
      interview format was used to elicit responses. SETTING: Interviews were conducted
      by phone with participants. PARTICIPANTS: All pharmacists who recently provided
      telephonic MTM services as a part of an RCT participated in this study.
      INTERVENTIONS: Pharmacists were asked questions regarding their perceptions of
      the services, training opportunities, patient perceptions of the services,
      interactions with physicians, and suggestions for improvement. General
      demographic information was collected for each pharmacist and summarized using
      descriptive statistics. Interview data were analyzed using inductive qualitative
      methods to reveal key themes related to facilitators and barriers of MTM services
      in home health care patients. MAIN OUTCOME MEASURES: The main outcome measures
      were major themes identified from pharmacist interviews pertaining to barriers,
      facilitators, and quality improvement strategies for telephonic MTM delivery.
      RESULTS: A total of four pharmacists (i.e., 100% of those who participated in the
      prior RCT) were interviewed. Several themes emerged from the analysis, including:
      communication and relationships, coordinating care and patient self-management,
      logistics, professional fulfillment, service delivery and content, and training
      opportunities. CONCLUSIONS: This study provides possible strategies to overcome
      barriers and facilitate service provision for future telephonic MTM services.

PMID- 25760667
TI  - Governors recommend expanding role for pharmacists.

PMID- 25760668
TI  - Fluorescent in situ hybridization shows DIPLOSPOROUS located on one of the NOR
      chromosomes in apomictic dandelions (Taraxacum) in the absence of a large
      hemizygous chromosomal region.
AB  - Apomixis in dandelions (Taraxacum: Asteraceae) is encoded by two unlinked
      dominant loci and a third yet undefined genetic factor: diplosporous omission of
      meiosis (DIPLOSPOROUS, DIP), parthenogenetic embryo development (PARTHENOGENESIS,
      PAR), and autonomous endosperm formation, respectively. In this study, we
      determined the chromosomal position of the DIP locus in Taraxacum by using
      fluorescent in situ hybridization (FISH) with bacterial artificial chromosomes
      (BACs) that genetically map within 1.2-0.2 cM of DIP. The BACs showed dispersed
      fluorescent signals, except for S4-BAC 83 that displayed strong unique signals as
      well. Under stringent blocking of repeats by C0t-DNA fragments, only a few
      fluorescent foci restricted to defined chromosome regions remained, including one
      on the nucleolus organizer region (NOR) chromosomes that contains the 45S rDNAs.
      FISH with S4-BAC 83 alone and optimal blocking showed discrete foci in the middle
      of the long arm of one of the NOR chromosomes only in triploid and tetraploid
      diplosporous dandelions, while signals in sexual diploids were lacking. This
      agrees with the genetic model of a single dose, dominant DIP allele, absent in
      sexuals. The length of the DIP region is estimated to cover a region of 1-10 Mb.
      FISH in various accessions of Taraxacum and the apomictic sister species
      Chondrilla juncea, confirmed the chromosomal position of DIP within Taraxacum but
      not outside the genus. Our results endorse that, compared to other model
      apomictic species, expressing either diplospory or apospory, the genome of
      Taraxacum shows a more similar and less diverged chromosome structure at the DIP
      locus. The different levels of allele sequence divergence at apomeiosis loci may
      reflect different terms of asexual reproduction. The association of apomeiosis
      loci with repetitiveness, dispersed repeats, and retrotransposons commonly
      observed in apomictic species may imply a functional role of these shared
      features in apomictic reproduction, as is discussed. 

PMID- 25760669
TI  - Homo- and heteronuclear compounds with a symmetrical bis-hydrazone ligand:
      synthesis, structural studies, and luminescent properties.
AB  - Nine new coordination compounds have been synthesized by the reaction of salts of
      bivalent metal ions (a=Zn(II) , b=Cu(II) , c=Ni(II) , d=Co(II) ) with the
      bis(benzoylhydrazone) derivative of 4,6-diacetylresorcinol (H4 L). Three kinds of
      complexes have been obtained: homodinuclear compounds [M2 (H2 L)2 ]?nH2 O (1 a, 1
      b, 1 c, and 1 d), homotetranuclear compounds [M4 (L)2 ]?n(solv) (2 a and 2 c),
      and heterotetranuclear compounds [Zn2 M2 (L)2 ]?n(solv) (2 ab, 2 ac, and 2 ad).
      The structures of the free ligand H4 L?2 DMSO and its complexes [Zn2 (H2 L)2
      (DMSO)2 ] (1 a*), [Zn4 (L)2 (DMSO)6 ] (2 a*), and [Zn0.45 Cu3.55 (L)2 (DMSO)6 ]?2
      DMSO (2 ab*) were elucidated by single-crystal X-ray diffraction. The ligand
      shows luminescence properties and its fluorimetric behavior towards M(II) metals
      (M=Zn, Cu, Ni and Co) has been studied. Furthermore, the solid-state luminescence
      properties of the ligand and compounds have been determined at room temperature.
      (1) H NMR spectroscopic monitoring of the reaction of H4 L with Zn(II) showed the
      deprotonation sequence of the OH/NH groups upon metal coordination. Heteronuclear
      reactions have also been monitored by using ESI-MS and spectrofluorimetric
      techniques.

PMID- 25760670
TI  - Comparative assessment of immunization coverage of migrant children between
      national immunization program vaccines and non-national immunization program
      vaccines in East China.
AB  - This study aimed to describe the disparities in immunization coverage between
      National Immunization Program (NIP) vaccines and non-NIP vaccines in Yiwu and to
      identify potential determinants. A face-to-face interview-based questionnaire
      survey among 423 migrant children born from 1 June 2010 to 31 May 2013 was
      conducted. Immunization coverage was estimated according to the vaccines
      scheduled at different age, the birth cohorts, and socio- demographic
      characteristics. Single-level logistic regression analysis was applied to
      identify the determinants of coverage of non-NIP vaccines. We found that NIP
      vaccines recorded higher immunization coverage compared with non-NIP vaccines
      (87.9100%- vs 0%-74.8%). Among the non-NIP vaccines, varicella vaccine (VarV)
      recorded the highest coverage of 85.4%, which was introduced in 1998; while 7
      valent pneumococcal conjugate vaccine(PCV7) recorded the lowest coverage of 0%
      for primary series, which was introduced recently. Lower coverage rate of non-NIP
      vaccines was significantly associated with more siblings in household, shorter
      duration of living in the surveyed areas, lower family income, mother with a job,
      mother with poor awareness of vaccination, and mother with lower education level.
      We found the immunization coverage rate of non-NIP vaccines was significant lower
      than that of NIP vaccines. Expansion of NIP to include non-NIP vaccines can
      provide better protection against the vaccine preventable diseases through
      increased immunization coverage.

PMID- 25760671
TI  - Clinical drug interaction profile of idelalisib in healthy subjects.
AB  - Idelalisib, a potent phosphatidylinositol-3-kinase delta (PI3Kdelta) inhibitor,
      is metabolized primarily by aldehyde oxidase to form GS-563117 and to a lesser
      extent by cytochrome P450 (CYP) 3A and uridine 5'-diphospho
      glucuronosyltransferase 1A4. In vitro, idelalisib inhibits P-glycoprotein (P-gp)
      and organic anion transporting polypeptides 1B1 and 1B3, and GS-563117 is a time
      dependent CYP3A inhibitor. This study enrolled 24 healthy subjects and evaluated
      (1) the effect of idelalisib on the pharmacokinetics (PK) of digoxin, a P-gp
      probe substrate, rosuvastatin, a breast cancer resistance protein, and
      OATP1B1/OATP1B3 substrate, and midazolam, a CYP3A substrate; and (2) the effect
      of a strong inducer, rifampin, on idelalisib PK. On treatment, the most common
      clinical adverse events (AEs) were headache and pyrexia. Grade 3 transaminase
      increases were observed in 5 of 24 subjects and were reversible. Two subjects had
      serious AEs after treatment completion (grade 3 pyrexia and/or drug-induced liver
      injury). Idelalisib coadministration did not affect digoxin and rosuvastatin PK.
      Coadministration with idelalisib increased plasma exposures of midazolam (138%
      and 437% for maximum observed plasma concentration [Cmax ] and area under the
      plasma concentration-time curve from time 0 extrapolated to infinity [AUCinf ],
      respectively), consistent with the in vitro finding of CYP3A inhibition by GS
      563117. Rifampin caused a substantial decrease in idelalisib (58% and 75%, Cmax
      and AUCinf , respectively) and GS-563117 exposures, indicating an enhanced
      contribution of CYP3A to idelalisib metabolism under a strongly induced state. 

PMID- 25760673
TI  - Access to coumarins by rhodium-catalyzed oxidative annulation of aryl
      thiocarbamates with internal alkynes.
AB  - A Rh-catalyzed annulation of aryl thiocarbamates with internal alkynes via C-H
      bond activation has been developed. This protocol provides a new route to 3,4
      disubstituted coumarins. 

PMID- 25760672
TI  - Air Pollution and Mortality in Seven Million Adults: The Dutch Environmental
      Longitudinal Study (DUELS).
AB  - BACKGROUND: Long-term exposure to air pollution has been associated with
      mortality in urban cohort studies. Few studies have investigated this association
      in large-scale population registries, including non-urban populations.
      OBJECTIVES: The aim of the study was to evaluate the associations between long
      term exposure to air pollution and nonaccidental and cause-specific mortality in
      the Netherlands based on existing national databases. METHODS: We used existing
      Dutch national databases on mortality, individual characteristics, residence
      history, neighborhood characteristics, and national air pollution maps based on
      land use regression (LUR) techniques for particulates with an aerodynamic
      diameter <= 10 MUm (PM10) and nitrogen dioxide (NO2). Using these databases, we
      established a cohort of 7.1 million individuals >= 30 years of age. We followed
      the cohort for 7 years (2004-2011). We applied Cox proportional hazard models
      adjusting for potential individual and area-specific confounders. RESULTS: After
      adjustment for individual and area-specific confounders, for each 10-MUg/m3
      increase, PM10 and NO2 were associated with nonaccidental mortality [hazard ratio
      (HR) = 1.08; 95% CI: 1.07, 1.09 and HR = 1.03; 95% CI: 1.02, 1.03, respectively],
      respiratory mortality (HR = 1.13; 95% CI: 1.10, 1.17 and HR = 1.02; 95% CI: 1.01,
      1.03, respectively), and lung cancer mortality (HR = 1.26; 95% CI: 1.21, 1.30 and
      HR = 1.10 95% CI: 1.09, 1.11, respectively). Furthermore, PM10 was associated
      with circulatory disease mortality (HR = 1.06; 95% CI: 1.04, 1.08), but NO2 was
      not (HR = 1.00; 95% CI: 0.99, 1.01). PM10 associations were robust to adjustment
      for NO2; NO2 associations remained for nonaccidental mortality and lung cancer
      mortality after adjustment for PM10. CONCLUSIONS: Long-term exposure to PM10 and
      NO2 was associated with nonaccidental and cause-specific mortality in the Dutch
      population of >= 30 years of age.

PMID- 25760674
TI  - Bisabolane Sesquiterpenoids from the Plant Endophytic Fungus Paraconiothyrium
      brasiliense.
AB  - Brasilamides E-J (1-6), the bisabolane sesquiterpenoids with the 3
      cyclohexylfuran (1 and 2) and 3-cyclohexylfuranone (3-6) skeletons, were isolated
      from the scale-up fermentation cultures of the plant endophytic fungus
      Paraconiothynium brasiliense Verkley. Although brasilamide E (1) is a known
      metabolite, its structure elucidation has yet to be described. The structures of
      1-6 were elucidated primarily by NMR experiments. Compounds 3-6 were found to be
      racemic, and 3 was further separated into enantiomers 3a and 3b on a chiral HPLC
      column. The absolute configurations of 3a and 3b were assigned by electronic
      circular dichroism calculations. Compound 1 selectively inhibited the
      proliferation of the breast (MCF-7) and gastric (MGC) cancer cell lines, with
      IC50 values of 8.4 and 14.7 MUM, respectively. Initial mechanistic investigation
      revealed that compound 1 inhibited the expression of a key energy metabolic
      enzyme, hexokinase II (HK2), in MCF-7 cells, which resulted in dysfunction of
      glucose metabolism and ATP depletion and eventually inhibited the proliferation
      of the breast cancer cells. 

PMID- 25760675
TI  - A model for aging under deformation field, residual stresses and strains in soft
      glassy materials.
AB  - A model is proposed that considers aging and rejuvenation in a soft glassy
      material as, respectively, a decrease and an increase in free energy. The aging
      term is weighted by an inverse of characteristic relaxation time suggesting that
      greater mobility of the constituents induces faster aging in a material. A
      dependence of relaxation time on free energy is proposed, which under quiescent
      conditions leads to a power law dependence of relaxation time on waiting time as
      observed experimentally. The model considers two cases, namely, a constant
      modulus when aging is entropy controlled and a time dependent modulus. In the
      former and the latter cases the model has, respectively, two and three
      experimentally measurable parameters that are physically meaningful. Overall, the
      model predicts how the material undergoes aging and approaches a rejuvenated
      state under the application of a deformation field. In particular, the model
      proposes distinctions between various kinds of rheological effects for different
      combinations of parameters. Interestingly, when the relaxation time evolution is
      stronger than linear, the model predicts various features observed in soft glassy
      materials such as thixotropic and constant yield stress, thixotropic shear
      banding, and the presence of residual stress and strain. 

PMID- 25760677
TI  - PGTools: A Software Suite for Proteogenomic Data Analysis and Visualization.
AB  - We describe PGTools, an open source software suite for analysis and visualization
      of proteogenomic data. PGTools comprises applications, libraries, customized
      databases, and visualization tools for analysis of mass-spectrometry data using
      combined proteomic and genomic backgrounds. A single command is sufficient to
      search databases, calculate false discovery rates, group and annotate proteins,
      generate peptide databases from RNA-Seq transcripts, identify altered proteins
      associated with cancer, and visualize genome scale peptide data sets using
      sophisticated visualization tools. We experimentally confirm a subset of
      proteogenomic peptides in human PANC-1 cells and demonstrate the utility of
      PGTools using a colorectal cancer data set that led to the identification of 203
      novel protein coding regions missed by conventional proteomic approaches. PGTools
      should be equally useful for individual proteogenomic investigations as well as
      international initiatives such as chromosome-centric Human Proteome Project (C
      HPP). PGTools is available at http://qcmg.org/bioinformatics/PGTools.

PMID- 25760678
TI  - Highly active, chemo- and regioselective Yb(II) and Sm(II) catalysts for the
      hydrophosphination of styrene with phenylphosphine.
AB  - Stable heteroleptic amido Yb(II) and Sm(II) complexes bearing aminoether
      phenolate ligands and devoid of coordinated solvent have been structurally
      characterized. They afford highly active, chemoselective and, in the case of
      monoadditions, 100 % anti-Markovnikov regiospecific catalysts (down to 0.04 mol %
      loading) for the hydrophosphination of styrene with PhPH2 under mild conditions. 

PMID- 25760679
TI  - Differential effects of phenylephrine and norepinephrine on peripheral tissue
      oxygenation during general anaesthesia: A randomised controlled trial.
AB  - BACKGROUND: Phenylephrine and norepinephrine are two vasopressors commonly used
      to counteract anaesthesia-induced hypotension. Their dissimilar working
      mechanisms may differentially affect the macro and microcirculation, and
      ultimately tissue oxygenation. OBJECTIVES: We investigated the differential
      effect of phenylephrine and norepinephrine on the heart rate (HR), stroke volume
      (SV), cardiac index (CI), cerebral tissue oxygenation (SctO2) and peripheral
      tissue oxygenation (SptO2), and rate-pressure product (RPP). DESIGN: A randomised
      controlled study. SETTING: Single-centre, University Medical Center Groningen,
      The Netherlands. PATIENTS: Sixty normovolaemic patients under balanced
      propofol/remifentanil anaesthesia. INTERVENTIONS: If the mean arterial pressure
      (MAP) dropped below 80% of the awake state value, phenylephrine (100 MUg + 0.5
      MUg kg(-1) min(-1)) or norepinephrine (10 MUg + 0.05 MUg kg(-1) min(-1)) was
      administered in a randomised fashion. MAIN OUTCOME MEASURES: MAP, HR, SV, CI,
      SctO2, SptO2 and rate-pressure product (RPP) analysed from 30 s before drug
      administration until 240 s thereafter. RESULTS: Phenylephrine and norepinephrine
      caused an equivalent increase in MAP [Delta = 13 (8 to 22) and Delta = 13 (9 to
      19) mmHg, respectively] and SV [Delta = 6 +/- 6 and Delta = 5 +/- 7 ml,
      respectively], combined with a significant equivalent decrease in HR (both Delta
      = -8 +/- 6 bpm), CI (both Delta = -0.2 +/- 0.3 l min(-1) m(-2)) and SctO2 and an
      unchanged RPP (Delta = 345 +/- 876 and Delta = 537 +/- 1076 mmHg min(-1)).
      However, SptO2 was slightly but statistically significantly (P < 0.05) decreased
      after norepinephrine [Delta  = -3 (-6 to 0)%] but not after phenylephrine
      administration [Delta = 0 (-1 to 1)%]. In both groups, SptO2 after vasopressor
      was still higher than the awake value. CONCLUSION: In normovolaemic patients
      under balanced propofol/remifentanil anaesthesia, phenylephrine and
      norepinephrine produced similar clinical effects when used to counteract
      anaesthesia-induced hypotension. After norepinephrine, a fall in peripheral
      tissue oxygenation was statistically significant, but its magnitude was not
      clinically relevant.

PMID- 25760680
TI  - Effect of glucose-insulin-potassium on hyperlactataemia in patients undergoing
      valvular heart surgery: A randomised controlled study.
AB  - BACKGROUND: Hyperlactataemia represents oxygen imbalance in the tissues and its
      occurrence during cardiac surgery is associated with adverse outcomes. Glucose
      insulin-potassium (GIK) infusion confers myocardial protection against ischaemia
      reperfusion injury and has the potential to reduce lactate release while
      improving its clearance. OBJECTIVES: The objective of this study is to compare
      the effect of GIK on the incidence of hyperlactataemia in patients undergoing
      valvular heart surgery. DESIGN: A randomised controlled study. SETTING: Single
      university teaching hospital. PATIENTS: One hundred and six patients scheduled
      for elective valvular heart surgery with at least two of the known risk factors
      for hyperlactataemia. INTERVENTION: Patients were randomly allocated to receive
      either GIK solution (insulin 0.1 IU kg(-1) h(-1) and an infusion of 30% dextrose
      and 80 mmol l(-1) potassium at 0.5 ml kg(-1) h(-1)) or 0.9% saline (control)
      throughout surgery. MAIN OUTCOME MEASURES: The primary outcome was the incidence
      of hyperlactataemia (lactate >= 4 mmol l(-1)) during the operation and until 24 h
      after the operation. Secondary outcomes included haemodynamic parameters, use of
      vasopressor or inotropic drugs, and fluid balance until 24 h postoperatively.
      Postoperative morbidity endpoints were also assessed. RESULTS: The incidences of
      hyperlactataemia were similar in the groups (32/53 patients in each of the
      control and GIK groups, P > 0.999). There were no intergroup differences in
      haemodynamic parameters, use of vasopressor and inotropic drugs, or fluid
      balance. The incidences of postoperative morbidity endpoints were similar in both
      groups. CONCLUSION: Despite its theoretical advantage, GIK did not provide
      beneficial effects in terms of the incidence of hyperlactataemia or outcome in
      patients undergoing valvular heart surgery. TRIAL REGISTRATION:
      Clinicaltrials.gov identifier: NCT01825720.

PMID- 25760681
TI  - Fluid replacement and respiratory function: comparison of whole blood with
      colloid and crystalloid: A randomised animal study.
AB  - BACKGROUND: Fluid replacement with blood products, colloids and crystalloids is
      associated with morbidity and mortality. Despite this, the consequences of fluid
      administration on airway and respiratory tissue properties are not fully
      understood. OBJECTIVE: Comparison of respiratory effects of fluid replacement
      with autologous blood (Group B), colloid (HES 6% 130/0.4, Group CO) or
      crystalloid solution (NaCl 0.9%, Group CR) after haemorrhage with separate
      assessments of airway resistance and respiratory tissue mechanics. DESIGN: A
      randomised study. SETTING: An experimental model of surgical haemorrhage and
      fluid replacement in rats. PARTICIPANTS: Anaesthetised, ventilated rats randomly
      allocated into three groups (Group B: n = 8, Group CO: n = 8, Group CR: n = 9).
      INTERVENTION: Animals were bled in six sequential steps, each manoeuvre targeting
      a loss of 5% of total blood volume. The blood loss was then replaced stepwise in
      a 1 : 1 ratio with one of the three fluids. MAIN OUTCOME MEASURE: After each
      step, airway resistance (Raw), tissue damping and elastance (H) were determined
      by forced oscillations. Oedema indices from lung weights and histology were also
      measured. RESULTS: Raw (mean +/- SD) decreased in all groups following blood loss
      (-20.3 +/- 9.5% vs. baseline, P < 0.05), and remained low following blood
      replacement (-21.7 +/- 14.5% vs. baseline, P < 0.05), but was normalised by
      colloid (5.5 +/- 10.7%, NS). Crystalloid administration exhibited an intermediate
      reversal effect (-8.4 +/- 14.7%, NS). Tissue viscoelasticity increased following
      both blood loss and replacement, with no evidence of a significant difference in
      H between Groups CO and CR. More severe oedema was observed in Groups CR and CO
      than in Group B (P < 0.05), with no difference between the colloid and
      crystalloid solutions. CONCLUSION: This model, which mimics surgical haemorrhage,
      yields no evidence of a difference between colloids and crystalloids with regard
      to the pulmonary consequences of blood volume restoration. Functional changes in
      the lung should not be a key concern when choosing fluid replacement therapy with
      these solutions.

PMID- 25760683
TI  - Satellite-based estimates of groundwater depletion in the Badain Jaran Desert,
      China.
AB  - Despite prevailing dry conditions, groundwater-fed lakes are found among the
      earth's tallest sand dunes in the Badain Jaran Desert, China. Indirect evidence
      suggests that some lakes are shrinking. However, relatively few studies have been
      carried out to assess the regional groundwater conditions and the fate of the
      lakes due to the remoteness and severity of the desert environment. Here we use
      satellite information to demonstrate an ongoing slow decrease in both lake level
      and groundwater storage. Specifically, we use Ice, Cloud, and land Elevation
      Satellite altimetry data to quantify water levels of the lakes and show overall
      decreases from 2003 to 2009. We also use water storage changes from the Gravity
      Recovery and Climate Experiment and simulated soil and water changes from the
      Global Land Data Assimilation System to demonstrate long-term groundwater
      depletion in the desert. Rainfall increase driven by climate change has increased
      soil water and groundwater storage to a certain degree but not enough to
      compensate for the long-term decline. If countermeasures are not taken to control
      the pumping, many lakes will continue to shrink, causing an ecological and
      environmental disaster in the fragile desert oases. 

PMID- 25760682
TI  - Efficient transduction of primary vascular cells by the rare adenovirus serotype
      49 vector.
AB  - Neointima formation and vascular remodeling through vascular smooth muscle cell
      migration and proliferation can limit the long-term success of coronary
      interventions, for example, in coronary artery bypass grafting (CABG). Ex vivo
      gene therapy has the potential to reduce unnecessary cell proliferation and limit
      neointima formation in vascular pathologies. To date, the species C adenovirus
      serotype 5 has been commonly used for preclinical gene therapy; however, its
      suitability is potentially limited by relatively poor tropism for vascular cells
      and high levels of preexisting immunity in the population. To avoid these
      limitations, novel species of adenovirus are being tested; here we investigate
      the potential of adenovirus 49 (Ad49) for use in gene therapy. Transduction of
      primary human vascular cells by a range of adenovirus serotypes was assessed;
      Ad49 demonstrated highest transduction of both vascular smooth muscle and
      endothelial cells. Gene transfer with Ad49 in vascular smooth muscle and
      endothelial cells was possible following short exposure times (<1 hr) and with
      low MOI, which is clinically relevant. Ex vivo delivery to surplus CABG tissue
      showed efficient gene transfer with Ad49, consistent with the in vitro findings.
      Luminal infusion of Ad49GFP into intact CABG samples ex vivo resulted in
      efficient vessel transduction. In addition, no seroprevalence rates to Ad49 were
      observed in a Scottish cohort of patients from cardiovascular clinics, thus
      circumventing issues with preexisting immunity. Our results show that Ad49 has
      tropism for vascular cells in vitro and ex vivo and demonstrate that Ad49 may be
      an improved vector for local vascular gene therapy compared with current
      alternatives.

PMID- 25760685
TI  - Boosting properties of 3D binder-free manganese oxide anodes by preformation of a
      solid electrolyte interphase.
AB  - Huge irreversible capacity loss prevents the successful use of metal oxide anodes
      in Li-ion full cells. Here, we focus on the critical prelithiation step and
      demonstrate the challenge of electrolyte decomposition on a pristine anode in a
      full cell. Both an electrochemical activation process (54 h) with Li metal and a
      new electrolytic process (75 min) without Li metal were used to preform complete
      solid electrolyte interphase (SEI) layers on 3 D binder-free MnOy -based anodes.
      The preformed SEI layers mitigated the electrolyte decomposition effectively and
      widened the working voltage for the MnOy /LiMn2 O4 full cell, which resulted in a
      big boost of the specific energy to 300 and 200 W h kgcathode (-1) , largely
      improved cycling stability, and much higher specific power (4200 W h kgtotal (-1)
      ) compared to conventional Li-ion batteries. Detailed characterization, such as
      cyclic voltammetry, scanning transmission electron microscopy, and FTIR
      spectroscopy, gives mechanistic insight into SEI preformation. This work provides
      guidance for the design of anode SEI layers and enables the application of oxides
      for Li-ion battery full cells. 

PMID- 25760684
TI  - Diaphragm muscle fiber weakness and ubiquitin-proteasome activation in critically
      ill patients.
AB  - RATIONALE: The clinical significance of diaphragm weakness in critically ill
      patients is evident: it prolongs ventilator dependency, and increases morbidity
      and duration of hospital stay. To date, the nature of diaphragm weakness and its
      underlying pathophysiologic mechanisms are poorly understood. OBJECTIVES: We
      hypothesized that diaphragm muscle fibers of mechanically ventilated critically
      ill patients display atrophy and contractile weakness, and that the ubiquitin
      proteasome pathway is activated in the diaphragm. METHODS: We obtained diaphragm
      muscle biopsies from 22 critically ill patients who received mechanical
      ventilation before surgery and compared these with biopsies obtained from
      patients during thoracic surgery for resection of a suspected early lung
      malignancy (control subjects). In a proof-of-concept study in a muscle-specific
      ring finger protein-1 (MuRF-1) knockout mouse model, we evaluated the role of the
      ubiquitin-proteasome pathway in the development of contractile weakness during
      mechanical ventilation. MEASUREMENTS AND MAIN RESULTS: Both slow- and fast-twitch
      diaphragm muscle fibers of critically ill patients had approximately 25% smaller
      cross-sectional area, and had contractile force reduced by half or more. Markers
      of the ubiquitin-proteasome pathway were significantly up-regulated in the
      diaphragm of critically ill patients. Finally, MuRF-1 knockout mice were
      protected against the development of diaphragm contractile weakness during
      mechanical ventilation. CONCLUSIONS: These findings show that diaphragm muscle
      fibers of critically ill patients display atrophy and severe contractile
      weakness, and in the diaphragm of critically ill patients the ubiquitin
      proteasome pathway is activated. This study provides rationale for the
      development of treatment strategies that target the contractility of diaphragm
      fibers to facilitate weaning.

PMID- 25760686
TI  - Kinetics of the Self Reaction of Cyclopentadienyl Radicals.
AB  - The kinetics of the self-reaction of cyclopentadienyl radicals (c-C5H5) was
      studied by laser photolysis/photoionization mass spectroscopy. Overall rate
      constants were obtained in direct real-time experiments in the temperature region
      304-600 K and at bath gas densities of (3.00-12.0) * 10(16) molecules cm(-3). The
      room-temperature value of the rate constant, (3.98 +/- 0.41) * 10(-10) cm(3)
      molecule(-1) s(-1), is significantly higher than the rate constants for most
      hydrocarbon radical-radical reactions and coincides with the estimated collision
      rate. The observed overall c-C5H5 + c-C5H5 rate constant demonstrates an
      unprecedented strong negative temperature dependence: k1 = 2.9 * 10(-12)
      exp(+1489 K/T) cm(3) molecule(-1) s(-1), with estimated uncertainty increasing
      with temperature, from 13% at 304 to 32% at 600 K. Formation of C10H10 as the
      primary product of cyclopentadienyl self-reaction was observed. In additional
      experiments performed at the temperature of 800 K, formation of C10H10, C10H9,
      and C10H8 was observed. Final product analysis by gas chromatography/mass
      spectrometry detected two isomers of C10H8 at 800 K: naphthalene (major) and
      azulene (minor). 

PMID- 25760688
TI  - Inhibition of microRNA-17/20a suppresses cell proliferation in gastric cancer by
      modulating UBE2C expression.
AB  - microRNAs (miRNAs) are small non-coding RNAs that potentially play a critical
      role in carcinogenesis. Increasing evidence indicates that the miR-17/20 cluster
      is upregulated in numerous types of human cancers including gastric cancer which
      suggests that the miR-17/20 cluster may play an important role in tumorigenesis.
      However, its role in gastric cancer carcinogenesis remains poorly defined due to
      the lack of target gene information. The aim of the present study was to
      investigate the target genes of the miR-17/20 cluster and their role in the tumor
      growth of gastric cancer. We found that both miR-17 and miR-20a (miR-17/20a)
      target the UBE2C gene in gastric cancer cells. Luciferase assay, qRT-PCR and
      western blot analysis confirmed that UBE2C is a direct target of miR-17/20a in
      gastric cancer cells. Our results showed that the expression of UBE2C was
      positively regulated by miR-17/20a at both the mRNA and protein levels. Moreover,
      miR-17/20a was upregulated and positively associated with UBE2C in the gastric
      cancer tissues when compared to the adjacent nontumor tissues. Inhibition of miR
      17/20a in gastric cancer cells was statistically correlated with a decrease in
      cell growth. These results demonstrate that upregulation of miR-17/20a promotes
      gastric cancer cell growth by targeting UBE2C and inhibition of their levels is a
      potentially promising therapeutic strategy for gastric cancer. 

PMID- 25760689
TI  - Task-sensitive reconfiguration of corticocortical 6-20 Hz oscillatory coherence
      in naturalistic human performance.
AB  - Electrophysiological oscillatory coherence between brain regions has been
      proposed to facilitate functional long-range connectivity within neurocognitive
      networks. This notion is supported by intracortical recordings of coherence in
      singled-out corticocortical connections in the primate cortex. However, the
      manner in which this operational principle manifests in the task-sensitive
      connectivity that supports human naturalistic performance remains
      undercharacterized. Here, we demonstrate task-sensitive reconfiguration of global
      patterns of coherent connectivity in association with a set of easier and more
      demanding naturalistic tasks, ranging from picture comparison to speech
      comprehension and object manipulation. Based on whole-cortex neuromagnetic
      recording in healthy behaving individuals, the task-sensitive component of long
      range corticocortical coherence was mapped at spectrally narrow-band oscillatory
      frequencies between 6 and 20 Hz (theta to alpha and low-beta bands). This data
      driven cortical mapping unveiled markedly distinct and topologically task
      relevant spatiospectral connectivity patterns for the different tasks. The
      results demonstrate semistable oscillatory states relevant for neurocognitive
      processing. The present findings decisively link human behavior to
      corticocortical coherence at oscillatory frequencies that are widely thought to
      convey long-range, feedback-type neural interaction in cortical functional
      networks.

PMID- 25760687
TI  - Inhibition of connexin 43 hemichannel-mediated ATP release attenuates early
      inflammation during the foreign body response.
AB  - BACKGROUND: In the last 50 years, the use of medical implants has increased
      dramatically. Failure of implanted devices and biomaterials is a significant
      source of morbidity and increasing healthcare expenditures. An important cause of
      implant failure is the host inflammatory response. Recent evidence implicates
      extracellular ATP as an important inflammatory signaling molecule. A major
      pathway for release of cytoplasmic ATP into the extracellular space is through
      connexin hemichannels, which are the unpaired constituents of gap junction
      intercellular channels. Blockade of hemichannels of the connexin 43 (Cx43)
      isoform has been shown to reduce inflammation and improve healing. We have
      developed a Cx43 mimetic peptide (JM2) that targets the microtubule-binding
      domain of Cx43. The following report investigates the role of the Cx43
      microtubule-binding domain in extracellular ATP release by Cx43 hemichannels and
      how this impacts early inflammatory events of the foreign body reaction. METHODS:
      In vitro Cx43 hemichannel-mediated ATP release by cultured human microvascular
      endothelial cells subjected to hypocalcemic and normocalcemic conditions was
      measured after application of JM2 and the known hemichannel blocker, flufenamic
      acid. A submuscular silicone implant model was used to investigate in vivo ATP
      signaling during the early foreign body response. Implants were coated with
      control pluronic vehicle or pluronic carrying JM2, ATP, JM2+ATP, or known
      hemichannel blockers and harvested at 24 h for analysis. RESULTS: JM2
      significantly inhibited connexin hemichannel-mediated ATP release from cultured
      endothelial cells. Importantly, the early inflammatory response to submuscular
      silicone implants was inhibited by JM2. The reduction in inflammation by JM2 was
      reversed by the addition of exogenous ATP to the pluronic vehicle. CONCLUSIONS:
      These data indicate that ATP released through Cx43 hemichannels into the
      vasculature is an important signal driving the early inflammatory response to
      implanted devices. A vital aspect of this work is that it demonstrates that
      targeted molecular therapeutics, such as JM2, provide the capacity to regulate
      inflammation in a clinically relevant system.

PMID- 25760690
TI  - Molecular characterization of LASP-1 expression reveals vimentin as its new
      partner in human hepatocellular carcinoma cells.
AB  - Hepatocellular carcinoma (HCC) is the third most common cause of cancer-related
      mortality worldwide. We have previously reported that LASP-1 is a downstream
      protein of the urokinase type plasminogen activator (uPA). Here we investigated
      the role of LASP-1 in HCC by a molecular and biological characterization of LASP
      1 expression in human HCC specimens and in cultured HCC cells. We determined the
      LASP-1 mRNA expression levels in 55 HCC cases with different hepatic background
      disease. We identified 3 groups of patients with high, equal or low LASP-1 mRNA
      levels in HCC tissues compared to the peritumoral (PT) tissues. In particular we
      found that i) the HCCs displayed a higher LASP-1 mRNA level in HCC compared to PT
      tissues; ii) the expression levels of LASP-1 mRNA in female HCCs were
      significantly higher compared to male HCCs; iii) the cirrhotic HCCs displayed a
      higher LASP-1 mRNA. Further, the biological characterization of the ectopic LASP
      1 overexpression in HCC cells, using MALDI-TOF mass spectrometer on the LASP-1 co
      immunoprecipitated fractions, displayed vimentin as a novel putative partner of
      LASP-1. Our results suggest that LASP-1 mRNA overexpression may be mainly
      implicated in female HCCs and cirrhotic HCCs; and that LASP1 may play its role
      with vimentin in HCC cells.

PMID- 25760692
TI  - Abuse-Deterrent Formulations and the Prescription Opioid Abuse Epidemic in the
      United States: Lessons Learned From OxyContin.
AB  - IMPORTANCE: In an effort to reduce wide-scale abuse of the proprietary oxycodone
      hydrochloride formulation OxyContin, an abuse-deterrent formulation (ADF) was
      introduced in 2010. Although the reformulation produced an immediate drop in
      abuse rates, a definite ceiling effect appeared over time, beyond which no
      further decrease was seen. OBJECTIVE: To examine the factors that led to the
      initial steep decline in OxyContin abuse and the substantial levels of residual
      abuse that have remained relatively stable since 2012. DESIGN, SETTING, AND
      PARTICIPANTS: We used data from the ongoing Survey of Key Informants' Patients
      program, part of the Researched Abuse, Diversion and Addiction-Related
      Surveillance system that collects and analyzes postmarketing data on misuse and
      diversion of prescription opioid analgesics and heroin. For our survey study,
      patients with a DSM-V diagnosis of opioid use disorder and primary drug of abuse
      consisting of a prescription opioid or heroin (N = 10,784) at entry to 1 of 150
      drug treatment programs in 48 states completed an anonymous structured survey of
      opioid abuse patterns (surveys completed from January 1, 2009, through June 30,
      2014). A subset of these patients (n = 244) was interviewed to add context and
      expand on the structured survey. MAIN OUTCOMES AND MEASURES: In addition to key
      demographic measures, past-month abuse of opioids was the primary measure in the
      structured surveys. In the interviews, the effect of the introduction of the ADF
      on drug-seeking behavior was examined. RESULTS: Reformulated OxyContin was
      associated with a significant reduction of past-month abuse after its
      introduction (45.1% [95% CI, 41.2%-49.1%] in January to June 2009 to 26.0% [95%
      CI, 23.6%-28.4%] in July to December 2012; P < .001; chi(2) = 230.83), apparently
      owing to a migration to other opioids, particularly heroin. However, this
      reduction leveled off, such that 25% to 30% of the sample persisted in endorsing
      past-month abuse from 2012 to 2014 (at study end [January to June 2014], 26.7%
      [95% CI, 23.7%-29.6%]). Among the 88 participants who indicated experience using
      pre-ADF and ADF OxyContin, this residual level of abuse reflects the following 3
      phenomena: (1) a transition from nonoral routes of administration to oral use (38
      participants [43%]); (2) successful efforts to defeat the ADF mechanism leading
      to a continuation of inhaled or injected use (30 participants [34%]); and (3)
      exclusive use of the oral route independent of formulation type (20 participants
      [23%]). CONCLUSIONS AND RELEVANCE: Abuse-deterrent formulations can have the
      intended purpose of curtailing abuse, but the extent of their effectiveness has
      clear limits, resulting in a significant level of residual abuse. Consequently,
      although drug abuse policy should focus on limiting supplies of prescription
      analgesics for abuse, including ADF technology, efforts to reduce supply alone
      will not mitigate the opioid abuse problem in this country.

PMID- 25760691
TI  - Fully human HER2/cluster of differentiation 3 bispecific antibody triggers potent
      and specific cytotoxicity of T lymphocytes against breast cancer.
AB  - The use of a bispecific antibody (BsAb) is a promising and highly specific
      approach to cancer therapy. In the present study, a fully human recombinant
      single chain variable fragment BsAb against human epidermal growth factor
      receptor (HER)2 and cluster of differentiation (CD)3 was constructed with the aim
      of developing an effective treatment for breast cancer. HER2/CD3 BsAb was
      expressed in Chinese hamster ovary cells and purified via nickel column
      chromatography. Flow cytometry revealed that the HER2/CD3 BsAb was able to
      specifically bind to HER2 and CD3-positive cells. HER2/CD3 BsAb was able to
      stimulate T-cell activation and induce the lysis of cultured SKBR-3 and BT474
      cells in the presence of unstimulated T lymphocytes. HER2/CD3 BsAb efficiently
      inhibited the growth of breast cancer tissue by activating and inducing the
      proliferation of tumor tissue infiltrating lymphocytes. Therefore, HER2/CD3 BsAb
      is a potent tool which may be a suitable candidate for the treatment of breast
      cancer. 

PMID- 25760693
TI  - Gene therapy strategies using engineered stem cells for treating gynecologic and
      breast cancer patients (Review).
AB  - There are three types of stem cells: embryonic stem (ES) cells, adult stem (AS)
      cells and induced pluripotent stem (iPS) cells. These stem cells have many
      benefits including the potential ability to differentiate into various organs. In
      addition, engineered stem cells (GESTECs) designed for delivering therapeutic
      genes may be capable of treating human diseases including malignant cancers. Stem
      cells have been found to possess the potential for serving as novel delivery
      vehicles for therapeutic or suicide genes to primary or metastatic cancer
      formation sites as a part of gene-directed enzyme/prodrug combination therapy
      (GEPT). Given the advantageous properties of stem cells, tissue-derived stem
      cells are emerging as a new tool for anticancer therapy combined with prodrugs.
      In this review, the effects of GESTECs with different origins, i.e., neural,
      amniotic membrane and amniotic fluid, introduced to treat patients with diverse
      types of gynecologic and breast cancers are discussed. Data from the literature
      indicate the therapeutic potential of these cells as a part of gene therapy
      strategies to selectively target malignancies in women at clinically terminal
      stages. 

PMID- 25760694
TI  - Severely obese adolescent girls rely earlier on carbohydrates during walking than
      normal-weight matched girls.
AB  - The purpose of this study was to determine the substrate oxidation rate and the
      exercise intensity at which maximal lipid oxidation and ventilatory threshold
      (VT) occur in obese (BMI: 36.6 +/- 6.3 kg . m(-2)) and normal-weight adolescent
      girls (BMI: 18.7 +/- 1.6 kg . m(-2)) aged 14-18 years. Substrate oxidation rate
      was determined by gas exchange using an incremental field test involving walking.
      Body composition was assessed by bioelectrical impedance. Carbohydrate oxidation
      rates were significantly higher in obese than in normal-weight girls at speeds
      ranging from 4 to 6 km . h(-1) (P < 0.05), whereas no significant differences
      were observed between groups regarding lipid oxidation rates. The crossover point
      of substrate utilisation and the VT were significantly lower in obese than in
      normal-weight adolescents (P < 0.05). Maximal lipid oxidation rate was observed
      at 46 +/- 15 and 53 +/- 15 %EVO2max in obese and normal-weight adolescents,
      respectively. At these intensities, the Lipox(max) was significantly lower in
      obese than in normal-weight girls (6.7 +/- 2.3 versus 8.9 +/- 3.5 mg . min(-1) .
      kg(-1) FFM, P < 0.05, 95% CI: -3.7 to -0.7, d = -0.74). The present results have
      implications in designing interventions to promote lipid oxidation and energy
      expenditure during walking in severely obese adolescent girls.

PMID- 25760695
TI  - The role of terahertz polariton absorption in the characterization of crystalline
      iron sulfate hydrates.
AB  - Iron sulfate compounds have been used extensively to produce iron gall ink, a
      widely used writing ink in the western world from the 12th-20th centuries. Iron
      gall ink is well known to corrode writing supports, so detection of iron species
      is important for the preservation of historical artwork and documents. Iron(ii)
      sulfate readily changes hydration states and oxidizes in ambient conditions,
      forming compounds that contribute to this deterioration. In this study, five
      forms of iron sulfate are characterized by terahertz spectroscopy and solid-state
      density functional theory (DFT). The results have revealed that the room
      temperature spectra of FeSO4.7H2O and FeSO4.4H2O are remarkably similar,
      differing by only a single absorption feature. The identifying terahertz spectra
      provide an unambiguous metric to determine the relative concentrations of the
      most common hydrates FeSO4.7H2O and FeSO4.4H2O in a mixed sample. Complete
      spectral assignments of these species were accomplished by quantum mechanical
      simulations, with the exception being a single anomalous feature at approximately
      40 cm(-1) in the heptahydrate. This peak is believed to be due to polariton
      absorption, brought about by the particular coordination structure of FeSO4.7H2O
      that results in a greater charge separation relative to the other iron sulfate
      crystals. 

PMID- 25760696
TI  - Competing risks and burn outcomes: more questions than answers.

PMID- 25760697
TI  - Origin and use of crystallization phase diagrams.
AB  - Crystallization phase diagrams are frequently used to conceptualize the phase
      relations and also the processes taking place during the crystallization of
      macromolecules. While a great deal of freedom is given in crystallization phase
      diagrams owing to a lack of specific knowledge about the actual phase boundaries
      and phase equilibria, crucial fundamental features of phase diagrams can be
      derived from thermodynamic first principles. Consequently, there are limits to
      what can be reasonably displayed in a phase diagram, and imagination may start to
      conflict with thermodynamic realities. Here, the commonly used 'crystallization
      phase diagrams' are derived from thermodynamic excess properties and their
      limitations and appropriate use is discussed. 

PMID- 25760698
TI  - Crystallization and preliminary X-ray crystallographic analysis of human
      myotubularin-related protein 1.
AB  - Myotubularin-related protein 1 is a phosphatase that dephosphorylates
      phospholipids such as phosphatidylinositol 3-phosphate or phosphatidylinositol
      3,5-bisphosphate. In this study, human MTMR1 was overexpressed in Escherichia
      coli, purified and crystallized at 277 K using polyethylene glycol 20,000 as a
      precipitant. Diffraction data were collected to 2.0 A resolution using
      synchrotron radiation. The crystals belonged to space group P1, with unit-cell
      parameters a = 67.219, b = 96.587, c = 97.581 A, alpha = 87.597, beta = 86.072,
      gamma = 77.327 degrees . Assuming the presence of four molecules in the
      asymmetric unit, the calculated Matthews coefficient value was 2.61 A(3) Da(-1)
      and the corresponding solvent content was 52.9%.

PMID- 25760699
TI  - Production, crystallization and X-ray diffraction analysis of a complex between a
      fragment of the TssM T6SS protein and a camelid nanobody.
AB  - The type VI secretion system (T6SS) is a machine evolved by Gram-negative
      bacteria to deliver toxin effectors into target bacterial or eukaryotic cells.
      The T6SS is functionally and structurally similar to the contractile tail of the
      Myoviridae family of bacteriophages and can be viewed as a syringe anchored to
      the bacterial membrane by a transenvelope complex. The membrane complex is
      composed of three proteins: the TssM and TssL inner membrane components and the
      TssJ outer membrane lipoprotein. The TssM protein is central as it interacts with
      both TssL and TssJ, therefore linking the membranes. Using controlled
      trypsinolysis, a 32.4 kDa C-terminal fragment of enteroaggregative Escherichia
      coli TssM (TssM32Ct) was purified. A nanobody obtained from llama immunization,
      nb25, exhibited subnanomolar affinity for TssM32Ct. Crystals of the TssM32Ct-nb25
      complex were obtained and diffracted to 1.9 A resolution. The crystals belonged
      to space group P64, with unit-cell parameters a = b = 95.23, c = 172.95 A.
      Molecular replacement with a model nanobody indicated the presence of a dimer of
      TssM32Ct-nb25 in the asymmetric unit.

PMID- 25760700
TI  - Purification, crystallization and preliminary X-ray diffraction studies of the
      beta-catenin homolog HMP-2 from Caenorhabditis elegans.
AB  - beta-Catenin is a multifunctional protein involved in both cell adhesion and Wnt
      signaling in metazoans. The nematode Caenorhabditis elegans is unusual in that it
      expresses four beta-catenin paralogs with separate functions. C. elegans HMP-2
      participates in cell adhesion but not in Wnt signaling, so structural and
      biochemical studies of this protein will help in understanding its unusual
      specialization and the evolution of beta-catenin. HMP-2 was expressed, purified
      and crystallized in two different salt conditions. Crystals grown from a sodium
      formate condition diffracted to a resolution of 2 A and belonged to space group
      C2, with unit-cell parameters a = 165.2, b = 39.0, c = 101.1 A, beta = 116.7
      degrees . Crystals obtained from a lithium sulfate condition diffracted to 3 A
      resolution and belonged to space group P43, with unit-cell parameters a = b =
      85.3, c = 138.7 A. Diffraction data were collected and processed from both
      crystal forms and the structure was solved by molecular replacement. Model
      refinement is in progress. 

PMID- 25760701
TI  - Structure of the dodecamer of the aminopeptidase APDkam598 from the archaeon
      Desulfurococcus kamchatkensis.
AB  - The crystal structure of the aminopeptidase APDkam589 from the thermophilic
      crenarchaeon Desulfurococcus kamchatkensis was determined at a resolution of 3.0
      A. In the crystal, the monomer of APDkam589 and its symmetry-related monomers are
      densely packed to form a 12-subunit complex. Single-particle electron-microscopy
      analysis confirms that APDkam589 is present as a compact dodecamer in solution.
      The APDkam589 molecule is built similarly to the molecules of the PhTET
      peptidases, which have the highest sequence identity to APDkam589 among known
      structures and were isolated from the more thermostable archaeon Pyrococcus
      horikoshii. A comparison of the interactions of the subunits in APDkam589 with
      those in PhTET1, PhTET2 and PhTET3 reveals that APDkam589 has a much lower total
      number of salt bridges, which correlates with the lower thermostability of
      APDkam589. The monomer of APDkam589 has six Trp residues, five of which are on
      the external surface of the dodecamer. A superposition of the structure of
      APDkam589 with those having a high sequence similarity to APDkam589 reveals that,
      although the positions of Trp45, Trp252 and Trp358 are not conserved in the
      sequences, the spatial locations of the Trp residues in these models are similar.

PMID- 25760702
TI  - Structures of Escherichia coli tryptophanase in holo and 'semi-holo' forms.
AB  - Two crystal forms of Escherichia coli tryptophanase (tryptophan indole-lyase,
      Trpase) were obtained under the same crystallization conditions. Both forms
      belonged to the same space group P43212 but had slightly different unit-cell
      parameters. The holo crystal form, with pyridoxal phosphate (PLP) bound to Lys270
      of both polypeptide chains in the asymmetric unit, diffracted to 2.9 A
      resolution. The second crystal form diffracted to 3.2 A resolution. Of the two
      subunits in the asymmetric unit, one was found in the holo form, while the other
      appeared to be in the apo form in a wide-open conformation with two sulfate ions
      bound in the vicinity of the active site. The conformation of all holo subunits
      is the same in both crystal forms. The structures suggest that Trpase is flexible
      in the apo form. Its conformation partially closes upon binding of PLP. The
      closed conformation might correspond to the enzyme in its active state with both
      cofactor and substrate bound in a similar way as in tyrosine phenol-lyase. 

PMID- 25760703
TI  - Crystallization and preliminary X-ray diffraction analysis of the arginine
      repressor ArgR from Bacillus halodurans.
AB  - The arginine repressor (ArgR) is a transcriptional regulator which regulates
      genes encoding proteins involved in arginine biosynthesis and the arginine
      catabolic pathway. ArgR from the alkaliphilic bacterium Bacillus halodurans was
      cloned and overexpressed in Escherichia coli. ArgR (Bh2777) from B. halodurans is
      composed of 149 amino-acid residues with a molecular mass of 16 836 Da. ArgR was
      crystallized at 296 K using 1,2-propanediol as a precipitant. Crystals of N
      terminally His-tagged ArgR were obtained by the sitting-drop vapour-diffusion
      method. Dehydrated crystals showed a dramatic improvement in diffraction quality
      and diffracted to 2.35 A resolution. The crystals belonged to the cubic space
      group I23, with unit-cell parameters a = b = c = 104.68 A. The asymmetric unit
      contained one monomer of ArgR, which generates a trimer by the threefold axis of
      the space group, giving a crystal volume per mass (VM) of 2.98 A(3) Da(-1) and a
      solvent content of 56.8%. 

PMID- 25760704
TI  - Cwp84, a Clostridium difficile cysteine protease, exhibits conformational
      flexibility in the absence of its propeptide.
AB  - In recent decades, the global healthcare problems caused by Clostridium difficile
      have increased at an alarming rate. A greater understanding of this antibiotic
      resistant bacterium, particularly with respect to how it interacts with the host,
      is required for the development of novel strategies for fighting C. difficile
      infections. The surface layer (S-layer) of C. difficile is likely to be of
      significant importance to host-pathogen interactions. The mature S-layer is
      formed by a proteinaceous array consisting of multiple copies of a high-molecular
      weight and a low-molecular-weight S-layer protein. These components result from
      the cleavage of SlpA by Cwp84, a cysteine protease. The structure of a truncated
      Cwp84 active-site mutant has recently been reported and the key features have
      been identified, providing the first structural insights into the role of Cwp84
      in the formation of the S-layer. Here, two structures of Cwp84 after propeptide
      cleavage are presented and the three conformational changes that are observed are
      discussed. These changes result in a reconfiguration of the active site and
      exposure of the hydrophobic pocket. 

PMID- 25760705
TI  - Mode of binding of the antithyroid drug propylthiouracil to mammalian haem
      peroxidases.
AB  - The mammalian haem peroxidase superfamily consists of myeloperoxidase (MPO),
      lactoperoxidase (LPO), eosinophil peroxidase (EPO) and thyroid peroxidase (TPO).
      These enzymes catalyze a number of oxidative reactions of inorganic substrates
      such as Cl(-), Br(-), I(-) and SCN(-) as well as of various organic aromatic
      compounds. To date, only structures of MPO and LPO are known. The substrate
      binding sites in these enzymes are located on the distal haem side.
      Propylthiouracil (PTU) is a potent antithyroid drug that acts by inhibiting the
      function of TPO. It has also been shown to inhibit the action of LPO. However,
      its mode of binding to mammalian haem peroxidases is not yet known. In order to
      determine the mode of its binding to peroxidases, the structure of the complex of
      LPO with PTU has been determined. It showed that PTU binds to LPO in the
      substrate-binding site on the distal haem side. The IC50 values for the
      inhibition of LPO and TPO by PTU are 47 and 30 uM, respectively. A comparision of
      the residues surrounding the substrate-binding site on the distal haem side in
      LPO with those in TPO showed that all of the residues were identical except for
      Ala114 (LPO numbering scheme), which is replaced by Thr205 (TPO numbering scheme)
      in TPO. A threonine residue in place of alanine in the substrate-binding site may
      affect the affinity of PTU for peroxidases. 

PMID- 25760706
TI  - Cloning, purification, crystallization and preliminary X-ray studies of a
      carbohydrate-binding module from family 64 (StX).
AB  - In recent years, biofuels have attracted great interest as a source of renewable
      energy owing to the growing global demand for energy, the dependence on fossil
      fuels, limited natural resources and environmental pollution. However, the cost
      effective production of biofuels from plant biomass is still a challenge. In this
      context, the study of carbohydrate-binding modules (CBMs), which are involved in
      guiding the catalytic domains of glycoside hydrolases to polysaccharides, is
      crucial for enzyme development. Aiming at the structural and functional
      characterization of novel CBMs involved in plant polysaccharide deconstruction,
      an analysis of the CAZy database was performed and CBM family 64 was chosen owing
      to its capacity to bind with high specificity to microcrystalline cellulose and
      to the fact that is found in thermophilic microorganisms. In this communication,
      the CBM-encoding module named StX was expressed, purified and crystallized, and X
      ray diffraction data were collected from native and derivatized crystals to 1.8
      and 2.0 A resolution, respectively. The crystals, which were obtained by the
      hanging-drop vapour-diffusion method, belonged to space group P3121, with unit
      cell parameters a = b = 43.42, c = 100.96 A for the native form. The phases were
      found using the single-wavelength anomalous diffraction method. 

PMID- 25760707
TI  - The structure of C290A:C393A Aurora A provides structural insights into kinase
      regulation.
AB  - Aurora A is a Ser/Thr protein kinase that functions in cell-cycle regulation and
      is implicated in cancer development. During mitosis, Aurora A is activated by
      autophosphorylation on its activation loop at Thr288. The Aurora A catalytic
      domain (amino acids 122-403) expressed in Escherichia coli autophosphorylates on
      two activation-loop threonine residues (Thr288 and Thr287), whereas a C290A,C393A
      double point mutant of the Aurora A catalytic domain autophosphorylates only on
      Thr288. The structure of the complex of this mutant with ADP and magnesium was
      determined to 2.1 A resolution using molecular replacement. This is an
      improvement on the existing 2.75 A resolution structure of the equivalent wild
      type complex. The structure confirms that single phosphorylation of the
      activation loop on Thr288 is insufficient to stabilize a 'fully active'
      conformation of the activation loop in the absence of binding to TPX2. 

PMID- 25760708
TI  - Crystallization and preliminary crystallographic analysis of acetophenone
      reductase from Geotrichum candidum NBRC 4597.
AB  - Acetophenone reductase (APRD) from Geotrichum candidium NBRC 4597 was
      crystallized by the hanging-drop vapour-diffusion method using PEG 3350 as a
      precipitant. The crystal belonged to space group P6522, with unit-cell parameters
      a = b = 104.5, c = 273.7 A, and diffracted to 2.6 A resolution. Phasing using the
      single-wavelength anomalous diffraction method was successful. Model building and
      crystallographic refinement are in progress. 

PMID- 25760709
TI  - Bacterial expression and preliminary crystallographic studies of a 149-residue
      fragment of human Caprin-1.
AB  - Caprin-1 is an RNA-binding protein which plays critical roles in several
      important biological processes, including cellular proliferation, the interferon
      mediated antiviral innate immune response, the maintenance of synaptic plasticity
      and the formation of RNA stress granules. Caprin-1 has been implicated in the
      pathogenesis of several human diseases, including osteosarcoma, breast cancer,
      viral infections, hearing loss and neurodegenerative disorders. Despite the
      emerging biological and physiopathological significance of Caprin-1, no
      structural information is available for this protein. Moreover, Caprin-1 does not
      have sequence similarity to any other protein with a known structure. It is
      therefore expected that structural studies will play a particularly crucial role
      in revealing the functional mechanisms of Caprin-1. Here, a protein fragment of
      human Caprin-1 consisting of residues 112-260 was expressed, purified and
      crystallized. Native and Se-SAD data sets were collected to resolutions to 2.05
      and 2.65 A, respectively, in different space groups. 

PMID- 25760710
TI  - Protein production, crystallization and preliminary X-ray analysis of two
      isoforms of the Dscam1 Ig7 domain.
AB  - Drosophila Down syndrome cell adhesion molecule 1 (Dscam1) plays a critical role
      in neural development. It can potentially form 38 016 isoforms through
      alternative RNA splicing, and exhibits isoform-specific homophilic interaction
      through three variable Ig domains (Ig2, Ig3 and Ig7). The diversity and
      homophilic interaction are essential for its functions. Ig7 has 33 isoforms and
      is the most variable among the three variable Ig domains. However, only one
      isoform of Ig7 (isoform 30) has been structurally determined to date. Here, two
      isoforms of Dscam1 Ig7 (isoforms 5 and 9; Ig75 and Ig79) were produced and
      crystallized. Diffraction data from Ig75 and Ig79 crystals were processed to
      resolutions of 1.95 and 2.37 A, respectively. Comparison of different Dscam1 Ig7
      isoforms will provide insight into the mechanism of its binding specificity. 

PMID- 25760711
TI  - Crystallization and preliminary X-ray analysis of the Plasmodium falciparum
      apicoplast DNA polymerase.
AB  - Infection by the parasite Plasmodium falciparum is the leading cause of malaria
      in humans. The parasite has a unique and essential plastid-like organelle called
      the apicoplast. The apicoplast contains a genome that undergoes replication and
      repair through the action of a replicative polymerase (apPOL). apPOL has no
      direct orthologs in mammalian polymerases and is therefore an attractive
      antimalarial drug target. No structural information exists for apPOL, and the
      Klenow fragment of Escherichia coli DNA polymerase I, which is its closest
      structural homolog, shares only 28% sequence identity. Here, conditions for the
      crystallization of and preliminary X-ray diffraction data from crystals of P.
      falciparum apPOL are reported. Data complete to 3.5 A resolution were collected
      from a single crystal (2 * 2 * 5 um) using a 5 um beam. The space group P6522
      (unit-cell parameters a = b = 141.8, c = 149.7 A, alpha = beta = 90, gamma = 120
      degrees ) was confirmed by molecular replacement. Refinement is in progress. 

PMID- 25760712
TI  - High-resolution crystal structure of a polyextreme GH43 glycosidase from
      Halothermothrix orenii with alpha-L-arabinofuranosidase activity.
AB  - A gene from the heterotrophic, halothermophilic marine bacterium Halothermothrix
      orenii has been cloned and overexpressed in Escherichia coli. This gene encodes
      the only glycoside hydrolase of family 43 (GH43) produced by H. orenii. The
      crystal structure of the H. orenii glycosidase was determined by molecular
      replacement and refined at 1.10 A resolution. As for other GH43 members, the
      enzyme folds as a five-bladed beta-propeller. The structure features a metal
      binding site on the propeller axis, near the active site. Based on thermal
      denaturation data, the H. orenii glycosidase depends on divalent cations in
      combination with high salt for optimal thermal stability against unfolding. A
      maximum melting temperature of 76 degrees C was observed in the presence of 4 M
      NaCl and Mn(2+) at pH 6.5. The gene encoding the H. orenii GH43 enzyme has
      previously been annotated as a putative alpha-L-arabinofuranosidase. Activity was
      detected with p-nitrophenyl-alpha-L-arabinofuranoside as a substrate, and
      therefore the name HoAraf43 was suggested for the enzyme. In agreement with the
      conditions for optimal thermal stability against unfolding, the highest
      arabinofuranosidase activity was obtained in the presence of 4 M NaCl and Mn(2+)
      at pH 6.5, giving a specific activity of 20-36 umol min(-1) mg(-1). The active
      site is structurally distinct from those of other GH43 members, including
      arabinanases, arabinofuranosidases and xylanases. This probably reflects the
      special requirements for degrading the unique biomass available in highly saline
      aqueous ecosystems, such as halophilic algae and halophytes. The amino-acid
      distribution of HoAraf43 has similarities to those of mesophiles, thermophiles
      and halophiles, but also has unique features, for example more hydrophobic amino
      acids on the surface and fewer buried charged residues. 

PMID- 25760713
TI  - Improved crystallization and diffraction of caffeine-induced death suppressor
      protein 1 (Cid1).
AB  - The post-transcriptional addition of uridines to the 3'-end of RNAs is an
      important regulatory process that is critical for coding and noncoding RNA
      stability. In fission yeast and metazoans this untemplated 3'-uridylylation is
      catalysed by a single family of terminal uridylyltransferases (TUTs) whose
      members are adapted to specific RNA targets. In Schizosaccharomyces pombe the TUT
      Cid1 is responsible for the uridylylation of polyadenylated mRNAs, targeting them
      for destruction. In metazoans, the Cid1 orthologues ZCCHC6 and ZCCHC11 uridylate
      histone mRNAs, targeting them for degradation, but also uridylate microRNAs,
      altering their maturation. Cid1 has been studied as a model TUT that has provided
      insights into the larger and more complex metazoan enzyme system. In this paper,
      two strategies are described that led to improvements both in the
      crystallogenesis of Cid1 and in the resolution of diffraction by ~1.5 A. These
      advances have allowed high-resolution crystallographic studies of this TUT system
      to be initiated. 

PMID- 25760714
TI  - Crystallization and preliminary X-ray analysis of Rv1674c from Mycobacterium
      tuberculosis.
AB  - Adaptations to hypoxia play an important role in Mycobacterium tuberculosis
      pathogenesis. Rv0324, which contains an HTH DNA-binding domain and a rhodanese
      domain, is one of the key transcription regulators in response to hypoxia. M.
      tuberculosis Rv1674c is a homologue of Rv0324. To understand the interdomain
      interaction and regulation of the HTH domain and the rhodanese domain,
      recombinant Rv1674c protein was purified and crystallized by the vapour-diffusion
      method. The crystals diffracted to 2.25 A resolution. Preliminary diffraction
      analysis suggests that the crystals belonged to space group P3121 or P3221, with
      unit-cell parameters a = b = 67.8, c = 174.5 A, alpha = beta = 90, gamma = 120
      degrees . The Matthews coefficient was calculated to be 2.44 A(3) Da(-1),
      assuming that the crystallographic asymmetric unit contains two protein
      molecules. 

PMID- 25760716
TI  - Incorporating variability in point estimates in risk assessment: Bridging the gap
      between LC50 and population endpoints.
AB  - Historically, point estimates such as the median lethal concentration (LC50) have
      been instrumental in assessing risks associated with toxicants to rare or
      economically important species. In recent years, growing awareness of the
      shortcomings of this approach has led to an increased focus on analyses using
      population endpoints. However, risk assessment of pesticides still relies heavily
      on large amounts of LC50 data amassed over decades in the laboratory. Despite the
      fact that these data are generally well replicated, little or no attention has
      been given to the sometime high levels of variability associated with the
      generation of point estimates. This is especially important in agroecosystems
      where arthropod predator-prey interactions are often disrupted by the use of
      pesticides. Using laboratory derived data of 4 economically important species (2
      fruit fly pest species and 2 braconid parasitoid species) and matrix based
      population models, the authors demonstrate in the present study a method for
      bridging traditional point estimate risk assessments with population outcomes.
      The results illustrate that even closely related species can show strikingly
      divergent responses to the same exposures to pesticides. Furthermore, the authors
      show that using different values within the 95% confidence intervals of LC50
      values can result in very different population outcomes, ranging from quick
      recovery to extinction for both pest and parasitoid species. The authors discuss
      the implications of these results and emphasize the need to incorporate
      variability and uncertainty in point estimates for use in risk assessment.

PMID- 25760715
TI  - Salinity stiffens the epidermal cell walls of salt-stressed maize leaves: is the
      epidermis growth-restricting?
AB  - As a result of salt (NaCl)-stress, sensitive varieties of maize (Zea mays L.)
      respond with a strong inhibition of organ growth. The reduction of leaf
      elongation investigated here has several causes, including a modification of the
      mechanical properties of the cell wall. Among the various tissues that form the
      leaf, the epidermis plays a special role in controlling organ growth, because it
      is thought to form a rigid outer leaf coat that can restrict elongation by
      interacting with the inner cell layers. This study was designed to determine
      whether growth-related changes in the leaf epidermis and its cell wall correspond
      to the overall reduction in cell expansion of maize leaves during an osmotic
      stress-phase induced by salt treatment. Two different maize varieties contrasting
      in their degree of salt resistance (i.e., the hybrids Lector vs. SR03) were
      compared in order to identify physiological features contributing to resistance
      towards salinity. Wall loosening-related parameters, such as the capacity of the
      epidermal cell wall to expand, beta-expansin abundance and apoplastic pH values,
      were analysed. Our data demonstrate that, in the salt-tolerant maize hybrid which
      maintained leaf growth under salinity, the epidermal cell wall was more
      extensible under salt stress. This was associated with a shift of the epidermal
      apoplastic pH into a range more favourable for acid growth. The more sensitive
      hybrid that displayed a pronounced leaf growth-reduction was shown to have
      stiffer epidermal cell walls under stress. This may be attributable to the
      reduced abundance of cell wall-loosening beta-expansin proteins following a high
      salinity-treatment in the nutrient solution (100 mM NaCl, 8 days). This study
      clearly documents that salt stress impairs epidermal wall-loosening in growth
      reduced maize leaves. 

PMID- 25760717
TI  - Decreasing birth weight is associated with adverse metabolic profile and lower
      stature in childhood and adolescence.
AB  - OBJECTIVE: We aimed to evaluate the association of birth weight SDS with insulin
      resistance, blood pressure, and auxology in children and adolescents born 23-42
      weeks of gestation. METHODS: We studied 143 singleton children and adolescents
      aged 9.3 +/- 3.3 years (range 2.0-17.9 years). Clinical assessments included
      insulin resistance measured by HOMA2-IR, auxology, and blood pressure from
      sphygmomanometer measurements. Continuous associations were examined, and
      stratified analyses carried out. For the latter, participants were divided into
      those of below-average birth weight (BABW, <0 SDS) and above-average birth weight
      (AABW, >=0 SDS). RESULTS: Irrespective of gestational age, lower birth weight SDS
      was associated with progressively greater HOMA2-IR (p<0.0001) and higher fasting
      insulin concentrations (p<0.0001). Decreasing birth weight SDS was associated
      with higher systolic (p = 0.011) and diastolic (p = 0.006) blood pressure. Lower
      birth weight SDS was also associated with decreasing stature (p<0.010). The BABW
      group was ~40% more insulin resistant than AABW participants (p = 0.004), with
      the former also displaying fasting insulin concentrations 37% higher (p = 0.004).
      BABW participants were 0.54 SDS shorter than those of higher birth weight (p =
      0.002). On average, BABW participants had not met their genetic potential,
      tending to be shorter than their parents (p = 0.065). As a result, when corrected
      for parents' heights, BABW participants were 0.62 SDS shorter than those born of
      higher birth weight (p = 0.001). Sub-group analyses on participants born
      appropriate-for-gestational-age (n = 128) showed that associations of birth
      weight SDS with both insulin resistance and stature remained (although
      attenuated). CONCLUSION: Decreasing birth weight SDS (even within the normal
      range) is associated with adverse metabolic profile and lower stature in children
      and adolescents.

PMID- 25760718
TI  - [Association between the frequency and duration, but not the intensity, of
      headache with mechanical hypersensitivity and the health of patients with tension
      type headache].
AB  - INTRODUCTION: The association between headache clinical parameters and other
      health-related and neuro-physiological outcomes is controversial. AIM: To
      investigate the association between headache frequency, duration and intensity
      with cranio-cervical pressure sensitivity considering the interaction of health
      related and physical outcomes. PATIENTS AND METHODS: Seventy-two individuals with
      tension type headache were included. A 1-month diary was used to assess headache
      frequency, duration and intensity. Pressure pain thresholds (PPT) and peri
      cranial tenderness to palpation, health-related quality of life (Short Form-36),
      disability, depression, and cervical range of motion were the outcomes. All
      outcomes were introduced into hierarchic logistic regression models to assess
      potential associations. RESULTS: Several associations between headache frequency
      and duration, but not intensity, with the remaining variables were found.
      Regression analysis showed that PPT over the temporalis muscle, bodily pain, age
      and physical role explained the 22.3% of the headache frequency, whereas general
      health, PPT over the upper trapezius and headache frequency explained 20% of
      headache duration (p < 0.001). CONCLUSIONS: This study found that headache
      frequency and duration, but not headache intensity, were associated with
      neurophysiological outcomes, e.g., cranio-cervical pressure sensitivity, and
      bodily pain in tension type headache. Other variables including age, physical
      role and general health were also associated with headache frequency and
      duration.

PMID- 25760719
TI  - [Care for patients with altered states of consciousness in a hospital for chronic
      and long-stay patients].
AB  - INTRODUCTION: Between 30% and 40% of patients with brain damage present
      alterations in their level of consciousness and, in some cases, altered states of
      consciousness: unresponsive wakefulness syndrome (UWS) or minimally conscious
      state (MCS). Recovery varies and survival is threatened by a number of
      complications. AIMS: The purpose of this study is to present the working
      methodology used at the Hospital La Pedrera (HLP) for patients in UWS or MCS and
      to analyse the clinical characteristics of the patients attended to, their
      progress, and the functional and cognitive situation at the time of their
      discharge from hospital. PATIENTS AND METHODS: The work consisted in a
      prospective descriptive study of patients seen at the HLP over the period 2009
      2013, who had been diagnosed with UWS or MCS. RESULTS: The HLP uses the case
      management method, offering integrated care dispensed by a multidisciplinary
      team. Patients are classified according to healthcare goals. Patients with UWS or
      MCS are included in the integrated care and adaptation programme. A total of 23
      patients (86.9% males) were attended to, the mean age being 54.9 years.
      Aetiology: brain haemorrhage, 30.4%; anoxic encephalopathy, 26.6%; metabolic
      encephalopathy, 17.3%; and other causes, 17.3%. Altogether 73.9% were admitted in
      UWS and the rest in MCS. COURSE: 43.4% improved their initial cognitive situation
      and 88.8% presented a situation of total dependence at the time of discharge. The
      most frequent complications were respiratory and urinary infections (53.6%).
      Death occurred in 65.2% of cases. CONCLUSIONS: Medical attention in UWS or MCS is
      complex and requires multidisciplinary care. Almost half of the patients improved
      their cognitive situation, which justifies a proactive attitude that attempts to
      improve the quality of life of both patients and their families.

PMID- 25760721
TI  - [Hemorrhagic colloid cyst of the third ventricle: fulminant deterioration].
AB  - INTRODUCTION: Colloid cysts are benign tumors of the third ventricle. Most of
      them remain asymptomatic. However, some patients can develop since intermittent
      headaches to an acute deterioration and even sudden death. Several theories exist
      for which there would be a sudden death in these patients, among which include
      the rapid increase in size of the cyst, its rupture, the disturbance of
      hypothalamus-mediated cardiovascular reflex control and the unusual bleeding of
      the cyst, with only 15 cases described in the literature. CASE REPORT: A 45 year
      old male with hypertension with acute hydrocephalus due to a hemorrhagic colloid
      cyst in the third ventricle. An external ventricular drain on each side was
      introduced and he was admitted to the ICU, where brain death was certified. After
      removal of the cyst through transcortical frontal approach, the diagnosis of
      colloid cyst with remains of hemolyzed blood was confirmed. CONCLUSION: Bleeding
      in colloid cysts is exceptional, and can occur in both symptomatic and
      asymptomatic patients, making it difficult to recognize this complication.

PMID- 25760720
TI  - [Visual epileptic seizures. Signs and symptoms, and clinical implications].
AB  - INTRODUCTION: Visual phenomena can be symptoms of epileptic seizures, although
      with an uncertain clinical meaning and relationship with the epileptogenic focus.
      AIMS: To describe the clinical implications of visual epileptic seizures
      according to their signs and symptoms in adults. PATIENTS AND METHODS: Data were
      collected consecutively over a period of one year from patients who reported
      visual signs and symptoms as the main manifestation of their seizures, and the
      visual symptoms are classified according to the characteristics of the
      description. RESULTS: The sample consisted of 78 patients, with a mean age of
      43.5 years. Focal epilepsy accounted for 97% of the cases. Of the 63% that were
      symptomatic epilepsies, 57% were vascular. The visual seizures were, in 81.9% of
      cases, the aura prior to the seizure, and 17.9% were isolated visual seizures.
      The coexistence of visual seizures and other types of seizure was associated to
      pharmacoresistance (p = 0.021). The visual symptoms reported were as follows:
      simple hallucinations (55.1%), illusions (23.1%), complex hallucinations (15.4%)
      and loss of vision (6.4%). The lobar localisation of the lesions was occipital
      (24.4%), temporoparietooccipital (21.8%), temporal (9%), parietal (3.8%) and
      frontal (1.3%). Occipital lesions were associated with simple visual
      hallucinations (p < 0.001), and visual illusions and complex visual
      hallucinations, with lesions affecting the temporoparietooccipital junction (p <
      0.05). Of the 55.1% of patients with a unilateral lesion in the magnetic
      resonance scan, 33% reported symptoms in the contralateral visual hemifield.
      CONCLUSIONS: Visual seizures mainly present as epileptic auras. Simple
      hallucinations are related with an occipital origin, whereas complex
      hallucinations are associated with more anterior regions of the brain. The
      appearance of lateralised visual phenomena suggests an origin located in the
      contralateral hemisphere.

PMID- 25760722
TI  - [Illness due the Ebola virus: epidemiology and clinical manifestations within the
      context of an international public health emergency].
AB  - INTRODUCTION: The epidemic caused by the Ebola virus in western Africa affects
      Guinea, Liberia, Sierra Leone, Nigeria, Mali and Senegal, and is the most serious
      to occur since the existence of this filovirus, which causes haemorrhagic fever,
      was first reported. This article reviews the epidemiological characteristics and
      clinical manifestations associated with the disease due to the Ebola virus.
      DEVELOPMENT: Until February 23, 2015 there have been 23,729 cases of Ebola, with
      a mortality rate of 40.1%. In the current epidemic, there are three ways the
      virus can be transmitted to human beings: contact with fluids and secretions from
      subjects already diagnosed with the disease, contact with dead bodies during
      burial ceremonies, and infection of relatives and healthcare personnel from as
      yet undiagnosed patients. Ebola is the cause of a serious disease in humans.
      Following a period of incubation that can vary in length (2-21 days), a syndrome
      involving fever, headache, aching muscles, sore joints, vomiting and diarrhoea
      begins. The advanced phase is accompanied by haemorrhages, multiple organ
      failure, hypotension and shock. The incidence of neurological manifestations is
      unknown, but brain haemorrhages and post-infectious syndromes have been reported
      in other viral haemorrhagic fevers. Support care is vital. No proven effective
      treatment exists, although several patients have been treated with a cocktail of
      monoclonal antibodies (ZMapp). CONCLUSIONS: Early identification and diagnosis of
      suspected cases, isolation of sick patients and protective measures among
      healthcare staff are fundamental in the control of this epidemic.

PMID- 25760724
TI  - [Epidural abscess due to Aspergillus fumigatus with compression of the optic
      nerve].

PMID- 25760725
TI  - [Tractography in Kernohan's phenomenon: report of a case of acute subdural
      haematoma].

PMID- 25760726
TI  - [In memoriam. Vernon B. Mountcastle (1918-2015)].

PMID- 25760727
TI  - FTIR study of thermally induced magnetostructural transitions in breathing
      crystals.
AB  - "Breathing crystals" based on copper(II) hexafluoroacetylacetonates and pyrazolyl
      substituted nitronyl nitroxides comprise the exchange-coupled clusters within the
      polymeric chains. Owing to an interplay of exchange interaction between
      copper(II) and nitroxide spins and Jahn-Teller nature of copper(II) complex, the
      breathing crystals demonstrate thermally and light-induced magnetostructural
      transitions in many aspects similar to the classical spin crossover. Herewith, we
      report the first application of variable temperature (VT) far/mid Fourier
      transform infrared (FTIR) spectroscopy and mid FTIR microscopy to breathing
      crystals. This VT-FTIR study was aimed toward clarification of the transitions
      mechanism previously debated on the basis of superconducting quantum interference
      device, X-ray diffraction, and electron paramagnetic resonance data. VT-FTIR
      showed the onset of new vibrational bands during phase transitions occurring at
      the expense of several existing ones, whose intensity was significantly reduced.
      The most pronounced spectral changes were assigned to corresponding vibrational
      modes using quantum chemical calculations. A clear-cut correlation was found
      between temperature-dependent effective magnetic moment of studied compounds and
      the observed VT-FTIR spectra. Importantly, VT-FTIR confirmed coexistence of two
      types of copper(II)-nitroxide clusters during gradual magnetostructural
      transition. Such clusters correspond to weakly coupled and strongly coupled spin
      states, whose relative contribution depends on temperature. The pronounced
      difference in the VT-FTIR spectra of two states in breathing crystals is a
      fingerprint of magnetostructural transition, and understanding of these
      characteristics achieved by us will be useful for future studies of breathing
      crystals as well as their diamagnetic analogues. 

PMID- 25760728
TI  - TRPM2 mediates histone deacetylase inhibition-induced apoptosis in bladder cancer
      cells.
AB  - PURPOSE: Inhibition of histone deacetylase (HDAC) activity results in growth
      arrest and apoptosis in multiple types of cancer cells. It has been well
      established that p21 is responsible for HDAC inhibitor (HDACi)-induced growth
      inhibition, while the mechanism underlying HDACi-elicited apoptosis in bladder
      cancer cells remains largely unknown. METHODS: In this study, the apoptotic
      response to HDACi (trichostatin A and sodium butyrate) with different
      concentrations was determined by flow cytometry analysis and real-time polymerase
      chain reaction was conducted to examine the TRPM2 (Transient receptor potential
      cation channel, subfamily M, member 2) expression change on HDACi treatment.
      TRPM2 knockdown and overexpression were performed to investigate the role of
      TRPM2 in HDACi-induced apoptosis. The mechanism of HDACi-elicited upregulation of
      TRPM2 was studied by chromatin-immunoprecipitation. RESULTS: HDACi efficiently
      induced cell apoptosis and TRPM2 upregulation in a time- and dose-dependent
      manner in T24 bladder cancer cells. Functional analysis revealed that TRPM2
      overexpression promotes apoptosis of T24 cells. Conversely, TRPM2 depletion
      remarkably antagonized HDACi-induced apoptosis. Furthermore, HDAC inhibition
      elicited TRPM2 upregulation is caused by the increase of acetylated H3K9 (H3K9Ac)
      enrichment in TRPM2 promoter. CONCLUSIONS: These data suggest that the HDACi
      elicited upregulation of TRPM2 expression is required for HDACi-induced apoptosis
      in bladder cancer cells and that HDACi activated the enrichment of H3K9Ac
      represented permissive chromatin in TRPM2 promoter.

PMID- 25760729
TI  - DNA methylation of DKK3 modulates docetaxel chemoresistance in human nonsmall
      cell lung cancer cell.
AB  - Dickkopf-related protein 3 (DKK3) gene, as a tumor suppressor gene, has been
      discovered in various cancers, but its relationship with tumor chemoresistance is
      still unclear. In this study, this laboratory detected that DNA methylation
      contributes to the downregulation of DKK3 in docetaxel resistance of human lung
      cancer cells and its possible biochemical mechanism. DKK3 has been proved to be
      downregulated by hypermethylation in docetaxel-resistant lung cancer cells.
      Upregulation of DKK3 can reverse the chemoresistance of docetaxel-resistant cell
      lines in vitro by growth inhibition and enhancement of apoptosis. Conversely,
      downregulation of DKK3 could induce parental human lung cancer cells
      insensitivity to docetaxel by promoting proliferative capacity and inhibiting
      apoptosis of cancer cells. In addition, the authors observed that overexpression
      of DKK3 might decrease the expression of P-glycoprotein. All results suggested
      that epigenetic downregulation of DKK3 leads to docetaxel resistance in human
      nonsmall cell lung cancer (NSCLC) cells by increased expression of P
      glycoprotein. DKK3 may reveal a novel molecular target for docetaxel resistance
      for NSCLC patients in the future. 

PMID- 25760730
TI  - Sol-gel synthesis and in vitro bioactivity of copper and zinc-doped silicate
      bioactive glasses and glass-ceramics.
AB  - Metal doping of bioactive glasses based on ternary 60SiO2-36CaO-4P2O5 (58S) and
      quaternary 60SiO2-25CaO-11Na2O-4P2O5 (NaBG) mol% compositions synthesized using a
      sol-gel process was analyzed. In particular, the effect of incorporating 1, 5 and
      10 mol% of CuO and ZnO (replacing equivalent quantities of CaO) on the texture,
      in vitro bioactivity, and cytocompatibility of these materials was evaluated. Our
      results showed that the addition of metal ions can modulate the textural property
      of the matrix and its crystal structure. Regarding the bioactivity, after soaking
      in simulated body fluid (SBF) undoped 58S and NaBG glasses developed an apatite
      surface layer that was reduced in the doped glasses depending on the type of
      metal and its concentration with Zn displaying the largest inhibitions. Both the
      ion release from samples and the ion adsorption from the medium depended on the
      type of matrix with 58S glasses showing the highest values. Pure NaBG glass was
      more cytocompatible to osteoblast-like cells (SaOS-2) than pure 58S glass as
      tested by 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT)
      assay. The incorporation of metal ions decreased the cytocompatibility of the
      glasses depending on their concentration and on the glass matrix doped. Our
      results show that by changing the glass composition and by adding Cu or Zn,
      bioactive materials with different textures, bioactivity and cytocompatibility
      can be synthesized. 

PMID- 25760731
TI  - Immune activation mediated by the late blight resistance protein R1 requires
      nuclear localization of R1 and the effector AVR1.
AB  - Resistance against oomycete pathogens is mainly governed by intracellular
      nucleotide-binding leucine-rich repeat (NLR) receptors that recognize matching
      avirulence (AVR) proteins from the pathogen, RXLR effectors that are delivered
      inside host cells. Detailed molecular understanding of how and where NLR proteins
      and RXLR effectors interact is essential to inform the deployment of durable
      resistance (R) genes. Fluorescent tags, nuclear localization signals (NLSs) and
      nuclear export signals (NESs) were exploited to determine the subcellular
      localization of the potato late blight protein R1 and the Phytophthora infestans
      RXLR effector AVR1, and to target these proteins to the nucleus or cytoplasm.
      Microscopic imaging revealed that both R1 and AVR1 occurred in the nucleus and
      cytoplasm, and were in close proximity. Transient expression of NLS- or NES
      tagged R1 and AVR1 in Nicotiana benthamiana showed that activation of the R1
      mediated hypersensitive response and resistance required localization of the
      R1/AVR1 pair in the nucleus. However, AVR1-mediated suppression of cell death in
      the absence of R1 was dependent on localization of AVR1 in the cytoplasm.
      Balanced nucleocytoplasmic partitioning of AVR1 seems to be a prerequisite. Our
      results show that R1-mediated immunity is activated inside the nucleus with AVR1
      in close proximity and suggest that nucleocytoplasmic transport of R1 and AVR1 is
      tightly regulated. 

PMID- 25760732
TI  - The evolution of your success lies at the centre of your co-authorship network.
AB  - Collaboration among scholars and institutions is progressively becoming essential
      to the success of research grant procurement and to allow the emergence and
      evolution of scientific disciplines. Our work focuses on analysing if the volume
      of collaborations of one author together with the relevance of his collaborators
      is somewhat related to his research performance over time. In order to prove this
      relation we collected the temporal distributions of scholars' publications and
      citations from the Google Scholar platform and the co-authorship network (of
      Computer Scientists) underlying the well-known DBLP bibliographic database. By
      the application of time series clustering, social network analysis and non
      parametric statistics, we observe that scholars with similar publications
      (citations) patterns also tend to have a similar centrality in the co-authorship
      network. To our knowledge, this is the first work that considers success
      evolution with respect to co-authorship. 

PMID- 25760733
TI  - The magnetohydrodynamic stagnation point flow of a nanofluid over a
      stretching/shrinking sheet with suction.
AB  - The magnetohydrodynamic (MHD) stagnation point flow of a nanofluid over a
      permeable stretching/shrinking sheet is studied. Numerical results are obtained
      using boundary value problem solver bvp4c in MATLAB for several values of
      parameters. The numerical results show that dual solutions exist for the
      shrinking case, while for the stretching case, the solution is unique. A
      stability analysis is performed to determine the stability of the dual solutions.
      For the stable solution, the skin friction is higher in the presence of magnetic
      field and increases when the suction effect is increased. It is also found that
      increasing the Brownian motion parameter and the thermophoresis parameter reduces
      the heat transfer rate at the surface. 

PMID- 25760734
TI  - Peptide-based allergen specific immunotherapy for the treatment of allergic
      disorders.
AB  - Allergen specific immunotherapy (ASIT) and environmental control are the only
      etiologic treatments of allergic rhino-conjunctivitis, asthma and atopic
      dermatitis. The clinical benefit of ASIT relies on the selection of the patients
      and the identification and administration of the allergen, or allergens.
      Different routes of administration have been investigated, including
      subcutaneous, intradermal, epicutaneous, sublingual, inhaled, or intra-lymphatic.
      While subcutaneous and sublingual allergen specific immunotherapy may require
      from 3 to 5 years of treatment, clinical efficacy with intra-lymphatic treatment
      can be achieved after 3 injections. The most severe side effect of ASIT is
      anaphylaxis. Novel approaches are being investigated to reduce the allergenicity
      of immunotherapy vaccines, maintaining immunogenicity. Peptide immunotherapy has
      been directed mostly against autoimmune diseases, but the use of synthetic
      peptides for ASIT is a promising field in basic science, applied immunology and
      in clinical development. Short synthetic peptides bear allergen-specific CD4 T
      cell epitopes which induce tolerance by stimulating regulatory (Treg) and Th1
      cells. In the present patent review, we describe new trends in allergen
      immunotherapy using peptides, which, from a clinical point of view, are
      promising. 

PMID- 25760735
TI  - Robotic total parathyroidectomy by the axillo-bilateral-breast approach for
      secondary hyperparathyroidism: a feasibility study.
AB  - BACKGROUND: The aim of this study was to evaluate the clinical application and
      superiority of the da Vinci((r)) Si Surgical System (Intuitive Surgical Inc.,
      Sunnyvale, CA) in total parathyroidectomy for secondary hyperparathyroidism.
      MATERIALS AND METHODS: Total parathyroidectomy was performed with the da Vinci Si
      Surgical System by the four-trocar axillo-bilateral-breast approach. The patients
      were placed in the supine position, and the operation procedure included creating
      the workspace, docking, and consoling stages. The camera arm is centered in the
      working space. Three working arms are then placed adjacent to the camera. The
      Harmonic((r)) scalpel (Ethicon Endo-surgery, Inc., Cincinnati, OH) was used for
      hemostasis and gland resection, and dissected parathyroid was taken out by a
      specimen pouch. RESULTS: Total parathyroidectomy with trace amounts of
      parathyroid tissue autotransplantation in 6 patients was successfully performed
      with the da Vinci Si Surgical System. There were no operation-related
      complications and no conversions to open or endoscopic surgery. Mean operation
      time was 156 minutes. Patients were discharged from the hospital 6 days after
      surgery. The postoperative cosmetic result was satisfactory, with minimal
      numbness and tingling on the anterior chest. CONCLUSIONS: This initial study
      shows that robotic total parathyroidectomy via the axillo-bilateral-breast
      approach is a safe and feasible alternative to selected patients, especially
      those with esthetic concerns.

PMID- 25760736
TI  - Bioinformatics analysis of abnormal DNA methylation in muscle samples from
      monozygotic twins discordant for type 2 diabetes.
AB  - The present study aimed to examine the changes in DNA methylation of gene
      promoters associated with type 2 diabetes (T2D). The DNA methylation profile
      dataset GSE38291 was downloaded from the Gene Expression Omnibus database. A
      paired t-test was used to analyze differences in the DNA methylation of gene
      promoters between T2D and normal muscle samples. Gene Ontology (GO) enrichment
      analysis was performed using online tool, The Database for Annotation,
      Visualization and Integrated Discovery. Whole-Genome rVISTA was used to analyze
      the enriched transcription factor (TF) binding sites upstream of the
      transcription start site in the differentially methylated genes. A total of 38
      genes, including Sirtuin 1, N-acetyltransferase 6, phospholipase A2 group XIIB
      and nuclear factor of activated T cells calcineurin-dependent 1, were identified
      to be differentially methylated between these two groups. One GO term, DNA
      geometric change (GO:0032392), was significantly enriched (P<0.05) by the hyper
      methylated genes. In addition, the binding sites of one gene, zinc finger E-box
      binding homeobox 1, and three TFs, methyl CpG binding protein 2, TFEB and TFAP4,
      were significantly enriched in the hyper- and hypo-methylated genes,
      respectively. The resulting T2D-associated genes and potential TFs provided a
      novel insight into the molecular mechanisms underlying the pathology of T2D.
      These genes may become promising target genes for the development of treatments
      for T2D.

PMID- 25760737
TI  - Rh-Catalysed direct cyclisation of 1,4-naphthoquinone and 9,10-phenanthraquinone
      with alkyne: facile access to 1,8-dioxapyrenes and 1,12-dioxaperylenes as orange
      and red-emitting luminophores.
AB  - Rh-catalysed direct cyclisation of 1,4-naphthoquinones and 9,10
      phenanthraquinones with alkynes has been accomplished for the first time through
      the C-H activation strategy to forge 1,8-dioxapyrenes and 1,12-dioxaperylenes.
      Starting from readily available substrates, a variety of dipyran-containing PAHs
      are obtained in one step and exhibit orange/red-emitting performance, large
      Stokes shifts and high thermal stability. 

PMID- 25760738
TI  - The Relationship Between Approach to Activity Engagement, Specific Aspects of
      Physical Function, and Pain Duration in Chronic Pain.
AB  - OBJECTIVES: To examine: (1) the relationships between habitual approach to
      activity engagement and specific aspects of physical functioning in chronic pain;
      and (2) whether or not these relationships differ according to pain duration.
      MATERIALS AND METHODS: Outpatients (N=169) with generalized chronic pain
      completed a set of written questionnaires. Categories of "approach to activity
      engagement" were created using the confronting and avoidance subscales of the
      Pain and Activity Relations Questionnaire. An interaction term between "approach
      to activity engagement" categories and pain duration was entered into analysis
      with age, sex, pain intensity, the categorical "approach to activity engagement"
      variable, and pain duration, in 9 ordinal regression models investigating
      functioning in a variety of daily activities. RESULTS: The "approach to activity
      engagement" category predicted the personal care, lifting, sleeping, social life,
      and traveling aspects of physical functioning but, interestingly, not the
      performance skills used during these activities, that is, walking, sitting, and
      standing. The interaction term was significant in 2 models; however, the effect
      of pain duration on associations was the inverse of that theorized, with the
      relationship between variables becoming less pronounced with increasing duration
      of pain. DISCUSSION: The results of this study do not support the commonly held
      notion that avoidance and/or overactivity behavior leads to deconditioning and
      reduced physical capacity over time. Findings do, however, suggest that a
      relationship exists between avoidance and/or overactivity behavior and reduced
      participation in activities. Implications for the clinical management of chronic
      pain and directions for further research are discussed.

PMID- 25760739
TI  - Is Spinal Cord Stimulation Useful and Safe for the Treatment of Chronic Pain of
      Ischemic Origin? A Review.
AB  - OBJECTIVES: The scope of this literature review was to assess the safety and the
      efficacy of spinal cord stimulation (SCS) for the treatment of chronic pain
      syndromes originating from refractory angina pectoris and peripheral vascular
      disease compared with conservative management. MATERIALS AND METHODS: A
      literature review was performed, which included randomized controlled trials and
      prospective controlled trials. PubMed searches were performed using terms such as
      SCS, RCT, vascular, VAS, heart, legs, limbs, and angina pectoris. Conservative
      management consisted of antihypertensive, vasodilator, or anticoagulant
      medications, analgesics, and local wound care. Seven trials met the inclusion and
      exclusion criteria. Each trial was analyzed during different follow-up periods to
      determine whether the mean reduction in the visual analog scale score associated
      with SCS treatment reached the minimal clinically important difference and/or the
      minimal significant difference associated with adequate pain management. The
      number and the rate of complications during different follow-up periods were also
      evaluated for each trial. RESULTS: The review demonstrated that SCS treatment
      provides in part long-term pain relief in otherwise intractable chronic pain of
      ischemic origin with a relatively low complication rate. DISCUSSION: SCS is a
      minimally invasive and reversible pain intervention. On the basis of the current
      literature, SCS may be an alternative treatment strategy in refractory angina
      pectoris and peripheral vascular disease patients, presenting a low surgical risk
      profile. However, further clinical trials with larger sample sizes and extended
      follow-up are required to confirm this finding.

PMID- 25760740
TI  - [Immediate response team. 59 cases with obstetric hemorrhage].
AB  - BACKGROUND: The lack of diagnosis as well as an appropriate medical and/or
      surgical treatment, due to an inefficient work team, contributes to the mortality
      associated to obstetric hemorrhage. The aim of this article is to analyze 59
      cases in which the immediate response team (ERI) was implemented in patient with
      obstetric hemorrhage. METHODS: Retrospective/prospective, observational, traverse
      and descriptive study in which 59 cases with obstetric hemorrhage and their
      attention by means of ERI. RESULTS: 59 patients with the diagnosis of obstetric
      hemorrhage were studied. The mean age of patients was 30.2 +/- 6.8 years. The
      main reason that originated the obstetric hemorrhage, was abruption placenta
      followed by uterine atony. The place in which where the ERI was more frequently
      implemented was the expulsion room and in 93.2 % of the cases the doctor was who
      begin it. In 71.2 % it was not necessary to transfuse globular package. Only one
      surgery was carried out in 52.5 % of the cases and two in 28.8 %. The 90.1 % of
      women didn't pass to intensive care unit, 8.5 % went in, and 1.7 % was
      transferred. CONCLUSIONS: According to the results obtained in this study the
      application of ERI was in a correct, integrated and standardized way.

PMID- 25760741
TI  - [Echocardiographic screening vs. symptomatic diagnosis for patent ductus
      arteriosus in preterms].
AB  - BACKGROUND: The persistence of ductus arteriosus, the aim of this study is to
      evaluate the possible benefit in the treatment for ductus closure when an early
      (less than 72 hours of life) echocardiographic screening is done versus when the
      echocardiographic diagnosis is realized only in present of associated symptoms.
      METHODS: Preterm without malformation followed by two strategies: patent ductus
      arteriosus (PDA) screening or echocardiographic study on suspected PDA for
      symptoms (control group). We analyzed the ductus characteristics, the presence of
      pulmonary hypertension and the treatments for their closure. We analyze the
      result in relation of the premature age as late preterm (34 to 36 gestational age
      weeks), moderate (30 to 33) and extreme (< 30). RESULTS: There was no difference
      in the proportion of newborns diagnosed with PDA among the strategies (screening
      18.6 % [101/543] vs 18.1 % [55/304], p = 0.92). In the control group, 53 % were
      diagnosed after 72 hours of life. There were no differences in relation of the
      ductus characteristic among the groups. The closure treatment were similar in the
      two strategies among the moderate and late preterm, but was more aggressive in
      the control group in the extreme preterms. CONCLUSIONS: The echocardiographic
      screening for PDA in extreme preterm newborns reduces the time to detect it, and
      allow to give less aggressive treatment. We do not recommend their use in
      moderate o late preterm newborn.

PMID- 25760742
TI  - [Efficacy and safety of initial treatment with glimpeiride versus sitagliptin in
      type 2 diabetes].
AB  - BACKGROUND: Diabetes mellitus type 2 (DM2) is a multifactorial disease that can
      be treated with oral antiglycemic medication or with insulin. The antiglycemic
      drugs glimepiride and sitagliptin have different mechanisms of action, and have
      not been directly compared in a Latin-American population with recent DM2
      diagnostic. METHODS: The primary objective in this randomized (1:1),
      multicentric, two arms, open study with adult patients, was to compare the
      efficacy of glimepiride with sitagliptin in a DM2 population naive to treatment.
      Secondary objectives had been the effect on fasting and postprandial glycemia,
      hypoglycemia, weight modification, safety, percentage of patients quiting the
      trial, vital signs and laboratory results. RESULTS: Glimepiride and sitagliptin
      were equally effective in glycemic control and all other parameters, and the only
      difference found has been the frequency of hypoglycemic events reports, wich has
      been reported as higher and statistically significant in the in the glimepiride
      group. No fatalities where reported in either group. CONCLUSIONS: Glimepiride or
      sitagliptin monotherapy are equally effective in control of HbA1c.

PMID- 25760743
TI  - [Adequate antimicrobial drug use in a third level pediatric hospital].
AB  - BACKGROUND: The inadequate use of antimicrobials contributes to the development
      of bacterial resistance, reduces the effectiveness of established treatments and
      increases costs and mortality due to infectious diseases. The aim of this article
      was to evaluate if the use of antimicrobials was carried out properly in
      hospitalized pediatric patients. METHODS: An epidemiological observational, cross
      sectional study was carried out in UMAE-48 in Leon, Guanajuato. Sample was non
      probabilistic by convenience with 60 % of expected adequate treatments, 4
      standard deviation. Analysis of statistical distribution frequency technique was
      used by type of final grade of each treatment that was administered: adequate,
      justified, therapeutic, restricted and prophylactic. The test chi-square test for
      comparing of percentages. RESULTS: Antimicrobial therapy were evaluated 283
      prescriptions in 217 patients, 53 % were men and 47 % women. The general
      treatment was adequate in 51.2 %, justified 66 %, therapeutic 53.4 %, 40.8 %
      restricted and 48% prophylactic. Comparison of percentages with statistical test
      of chi-square test, we found association with adequate treatment in neonates
      service (chi-square test 8.287; p 0.004) and inadequate treatment in preterm
      infants service (chi-square test 4.853; p 0.028) p < 0, 05. The most commonly
      used antimicrobials, 43.7 % penicillins and 37.1 % aminoglycoside. CONCLUSION:
      Only half of the treatments was antimicrobials are prescribed properly.

PMID- 25760744
TI  - [Detection of antileptospira antibodies in a vulnerable population of
      Ixhuatlancillo, Veracruz].
AB  - OBJECTIVE: To determine the seroprevalence of Leptospira sp. in Ixhuatlancillo
      residents and their canine pets. METHODS: We detected the presence of anti
      leptospira antibodies in a population of 29 dogs and 36 canine owners, the study
      consisted in two phases: 1) Management, invitation and application of surveys; 2)
      sampling to canines and positive canine owners. The samples were analyzed on the
      Veracruz State Laboratory, employing the microagglutination technique (MAT).
      Statistical analysis was performed using a 2 x 2 contingency table in order to
      know the relationship between two variables to test the possible independence of
      the two variables using the chi-square test. RESULTS: Prevalence of anti
      leptospira antibodies in dogs was 66 %, predominantly tarassovi serovar (47 %);
      and the owners analyzed prevalence was 61 %, which also tarassovi serovar was
      most prevalent (78 %). CONCLUSIONS: Anti-leptospira antibodies were found in dogs
      (66 %) and its owners; the tarassovi serovar was the most prevalent, so that
      living with pets is a potent risk factor for infection by this bacterium.

PMID- 25760745
TI  - [Pertussis in Mexico, an epidemiological overview. A study of 19 years at the
      Instituto Mexicano del Seguro Social].
AB  - BACKGROUND: Bordetella pertussis infection remains a public health problem in
      several developed and developing we describe the epidemiological syndrome cases
      subsystem special surveillance of whooping cough from 1992 to 2011 at a
      population with social security. METHODS: We obtained special cases subsystem
      Pertussis surveillance of 1992-2011. Univariate analysis was made of rates,
      ratios and proportions. Wilson was determined test for proportions to an alpha of
      0.05, t-test for mean difference. RESULTS: We appreciate epidemic cycles every
      three to five years, the average baseline incidence, excluding epidemic years,
      0.1 is considered confirmed cases per 100 000 beneficiaries assigned to family
      medicine, the highest incidence was recorded in 1997 and 2009. The most affected
      were children under 1 year of age and in outbreaks, the disease occurred at older
      ages. CONCLUSIONS: During the period observed intermediate epidemic cycles 5 and
      3 years of age presentation is consistent in other countries.

PMID- 25760746
TI  - [Safety nonsteroidal antiinflammatory drugs].
AB  - The choice of a specific medication belonging to a drug class is under the
      criteria of efficacy, safety, cost and suitability. NSAIDs currently constitute
      one of the most consumed drug in the world, so it is very important review of the
      safety aspects of this drug class. This review has the objective of analyze the
      safety of NSAIDs on 3 main criteria: gastrolesivity, cardiotoxicity and
      nephrotoxicity. 

PMID- 25760747
TI  - [Skin diseases and obesity].
AB  - Obesity is a public health problem worldwide. It predominates in industrialized
      countries; however, it is prevalent in all nations. It is defined as a condition
      of excess adipose tissue and is the result of changes in lifestyle, excessive
      consumption of energy-dense foods with poor nutritional value, physical
      inactivity and the reduction of open space where one can practice a sport.
      Although obesity is associated with multiple diseases, it is important to stress
      that the metabolic changes caused by it affect skin physiology and play a
      predisposing factor for the development of skin diseases. Very little has been
      studied on the impact of obesity on the skin. The purpose of this article is to
      review the most frequently skin diseases in obesity. Some skin pathologies in
      obesity are caused by changes in skin physiology, others are related to insulin
      resistance or constitute an exacerbating factor for dermatitis. This article
      covers the clinical features of obesity related skin disease and its management. 

PMID- 25760748
TI  - [Management of hyperglycemia in hospitalized patients].
AB  - Diabetes is a global health problem and Mexico rank sixth in prevalence of this
      entity. In our country, is the leading cause of death and is a major cause of
      hospital care being responsible for about 1 in 5 discharges. In the hospital
      setting, it has been observed that hyperglycemia, both diabetic and non-diabetic
      patients, is associated with an increased risk of complications, disability and
      death, and that adequate control in the blood glucose level produces a reduction
      in these complications. With these bases, several associations have recommended
      the treatment of hospital hyperglycemia through insulin administration, with the
      therapeutic goal of maintaining a fasting blood glucose level between 100-140
      mg/dL and glucose at any time of day less than 180 mg/dL. The insulin application
      method most recommended consisting in a basal-bolus regimen which has shown
      efficacy with a low risk of hypoglycemia. The usual practice of the application
      of insulin through a correction scheme should be abandoned because it is
      inefficient and involves risks. 

PMID- 25760749
TI  - [Situational panorama of Mexico against the chikungunya virus pandemic].
AB  - Recent outbreaks of emerging diseases emphasize the vulnerability of health
      systems, as is the case of chikungunya fever. The wide geographical incidence of
      the virus in the last years requires alerting systems for the prevention,
      diagnosis, control and eradication of the disease. Given the ecological,
      epidemiological and socio-economic characteristic of Mexico, this disease affects
      directly or indirectly the health of the population and development of
      agricultural, livestock, industrial, fishing, oil and tourism activities in the
      country. Due to this situation it is essential to make a brief analysis on the
      main clinical data, epidemiological and preventive measures with which our
      country counts with to confront the situation. 

PMID- 25760750
TI  - [Perception of health and safety risks among workers pathology laboratories].
AB  - BACKGROUND: Health care workers are experiencing increasing numbers of
      occupational illnesses. Safety practices in anatomical pathology laboratories
      (APL) are crucial to prevent unnecessary exposures to both chemical and
      biological agents. METHODS: The main goal of this study was to determine if
      pathologists perceptions and actual practice mirror regulatory guidelines.
      Current available recommendations for APL were reviewed and used to construct an
      online survey distributed to pathologists. The survey was completed by 121
      participants. RESULTS: Eighty-seven (72 %) of respondents reported receiving
      inadequate safety training. Most pathologists (82 %) were not well-informed about
      biosafety practices. Sixty-three (52 %) participants felt that the risks of
      chemical and infectious disease exposures in the APL were low. Most respondents
      reported having a needle stick or cut (71 %). Eighty-six (71 %) of participants
      reported musculo skeletal problems. CONCLUSIONS: This study indicated that there
      is a need for improving training in anatomical pathology safety practices in
      Mexican laboratories as daily practices do not reflected current guidelines.

PMID- 25760751
TI  - [Clinical practice guideline. Diagnosis and treatment of postmenopausal and
      perinemopausia].
AB  - Post-menopause is the period of life where a deep decline occurs in circulating
      estrogen levels, inducing the appearance of psycho and somatic symptoms. The
      classification to understand the chronology of reproductive aging in women (known
      as STRAW) determines the clinical and endocrine changes contemplating menstrual
      cycles, symptoms, measurements of FSH, LH, inhibin B, anti-Mullerian hormone ,
      and follicular account. The diagnosis of menopause is established by the absence
      of menstruation for 12 months or more. The most frequent clinical manifestations
      of the climacteric syndrome transition to menopause are menstrual disorders,
      vasomotor symptoms (flushes and/or sweats) and genitourinary manifestations. The
      assessment of women in the peri- or postmenopause aims to develop: cervicovaginal
      cytology , lipid profile , serum glucose, basal Mammography at least a year
      before, pelvic ultrasound, urinalysis, serum TSH, Densitometry in patients older
      than 60 years if there is no recourse can be applied and FRAX. Drug therapy for
      the treatment of disorders of the transition to menopause or menopause is divided
      into: hormone therapy (HT) based estrogens and progestin hormone not being the
      most recommended the serotonin reuptake inhibitors and norepinephrine, clonidine,
      gabapentin or veralipride. 

PMID- 25760752
TI  - [Anomalous origin of the left coronary artery from the opposite breast.
      Pathological case].
AB  - BACKGROUND: Anomalous origin of the left coronary artery from right coronary
      sinus ACAOS is characterized because the left main coronary artery anomalously
      originates from the right sinus of valsalva aortic coronary and whose journey can
      follow four different paths to the left side of the heart. CASE REPORT: A 73
      years old men, who was admitted at the hospital for chest pain of oppressive
      type, intensity 10/10 with irradiation to left arm and neck, accompanied by
      diaphoresis and nausea. The diagnosis was an ischemic syndrome acute coronary
      undergo therapy thrombolytic, the evolution was not satisfactory due to different
      complications that led to the death. CONCLUSIONS: The diagnosis of anomalous
      coronary artery left the opposite breast origin (ACAOS), is established basically
      through methods of diagnostics as computed cardiac angiography or cardiac
      catheterization as part of the approach of an acute coronary ischemic syndrome
      that allow to establish the morphological characteristics of coronary as the
      different anatomic variants and their characteristics with respect to adjacent
      structures.

PMID- 25760753
TI  - [Atypical presentation of diffuse large B-cell non-Hodgkin lymphoma].
AB  - The non-Hodgkin lymphoma is a neoplastic entity that presents in extranodal form
      in 20 % of cases, usually occurs as solitary or generalized lymphadenopathy.
      There may be misdiagnosis if it manifests as primary extranodal disease because
      the primary infiltration may occur with different organs, despite the difficulty
      of diagnosis of primary extranodal location of non-Hodgkin lymphoma, histological
      and immunohistochemical studies are effective in preventing misdiagnosis. The
      presentation of this case is to describe this condition in its extranodal variety
      with cardiac infiltration in a 23 year-old woman with progressive dyspnea. Tumor
      mass was detected in right-atrial, venous catheterization biopsy was performed,
      this enabled the histopathological diagnosis and establish treatment. We present
      experiences from the attention of the case and review of the literature with
      special reference to diagnosis and treatment. 

PMID- 25760755
TI  - [Underestimation of dermatology based on ignorance and its impact on patient's
      health].
AB  - With the emergence of medical specialties in different areas of medicine,
      assessment of patients became narrow and specialized. There is also the
      perception that some specialties are more difficult than others. Dermatology has
      long been seen by most physicians non dermatologists as a relaxed area, without
      real emergencies or requirement of great intellectual effort. Some specialists,
      erroneously think that everything can be cured with topical steroids and/or
      antifungal creams. Although several skin diseases are common complains seen by
      the general practitioner, very few time and credits are granted to cover these
      diseases during the years of undergraduate training. Thus, the primary care
      physicians and others medical specialists believe that skin diseases are not life
      threatening and hence irrelevant. Nonetheless, they feel competent enough to
      prescribe a variety of treatments for skin diseases that may lead to
      iatrogenesis. 

PMID- 25760754
TI  - [Obesity in Mexico].
AB  - Excess body weight (overweight and obesity) is currently recognized as one of the
      most important challenges of public health in the world, given its size, speed of
      growth and the negative effect it has on the health of the population that
      suffers. Overweight and obesity significantly increases the risk of chronic no
      communicable diseases, premature mortality and the social cost of health. An
      estimated 90 % of cases of type 2 diabetes mellitus attributable to overweight
      and obesity. Today, Mexico is second global prevalence of obesity in the adult
      population, which is ten times higher than that of countries like Japan and
      Korea. With regard to children, Mexico ranks fourth worldwide obesity prevalence,
      behind Greece, USA and Italy. In our country, over 70 % of the adult population,
      between 30 and 60 years are overweight. The prevalence of overweight is higher in
      men than females, while the prevalence of obesity is higher in women than men.
      Until 2012, 26 million Mexican adults are overweight and 22 million obese, which
      represents a major challenge for the health sector in terms of promoting healthy
      lifestyles in the population and development of public policies to reverse this
      scenario epidemiology. Mexico needs to plan and implement strategies and action
      cost effective for the prevention and control of obesity of children, adolescents
      and adults. Global experience shows that proper care of obesity and overweight,
      required to formulate and coordinate multisectoral strategies and efficient for
      enhancing protective factors to health, particularly to modify individual
      behavior, family and community. 

PMID- 25760756
TI  - Overview of single-cell elastic light scattering techniques.
AB  - We present and discuss several modern optical methods based on elastic light
      scattering (ELS), along with their technical features and applications in
      biomedicine and life sciences. In particular, we review some ELS experiments at
      the single-cell level and explore new directions of applications. Due to recent
      developments in experimental systems (as shown in the literature), ELS lends
      itself to useful applications in the life sciences. Of the developed methods, we
      cover elastic scattering spectroscopy, optical tweezer-assisted measurement,
      goniometers, Fourier transform light scattering (FTLS), and microscopic methods.
      FTLS significantly extends the potential analysis of single cells by allowing
      monitoring of dynamical changes at the single-cell level. The main aim of our
      review is to demonstrate developments in the experimental investigation of ELS in
      single cells including issues related to theoretical "representations" and
      modeling of biological systems (cells, cellular systems, tissues, and so on).
      Goniometric measurements of ELS from optically trapped single cells are shown and
      the importance of the experimental verification of theoretical models of ELS in
      the context of biomedical applications is discussed.

PMID- 25760757
TI  - An Initial Investigation of the Relationship Between Insomnia and Hoarding.
AB  - OBJECTIVE: Insomnia has been shown to have profound negative consequences on
      multiple aspects of daily functioning. Despite increased interest in the
      association between insomnia and psychopathology, no research has examined the
      relationships between insomnia and hoarding. The aim of the current investigation
      was to examine the associations between insomnia and hoarding severity. METHODS:
      Participants consisted of patients with hoarding disorder (n = 24). RESULTS:
      Results revealed that insomnia was a significant predictor of increased hoarding
      severity. In addition, when examining the relationships among insomnia and
      specific hoarding symptoms, sleep difficulties were associated with increased
      acquiring and difficulty discarding behaviors. CONCLUSIONS: These findings add to
      a growing body of literature on insomnia and various forms of psychopathology, as
      well as research on symptoms related to hoarding. Reducing insomnia symptoms
      among hoarders may help to reduce hoarding-related behaviors and increase
      treatment efficacy.

PMID- 25760758
TI  - Zanthoxylum schinifolium leaf ethanol extract inhibits adipocyte differentiation
      through inactivation of the extracellular signal regulated kinase and
      phosphoinositide 3-kinase/Akt signaling pathways in 3T3-L1 pre-adipocytes.
AB  - Zanthoxylum schinifolium is widely used as a food flavoring in east Asia.
      Although this plant has also been used in traditional oriental medicine for the
      treatment of the common cold, toothache, stomach ache, diarrhea and jaundice, its
      anti-obesity activity remains to be elucidated. The present study investigated
      the effects of ethanol extract from the leaves of Z. schinifolium (EEZS) on
      adipocyte differentiation, and its underlying mechanism, in 3T3-L1 pre
      adipocytes. The results demonstrated that EEZS effectively suppressed
      intracellular lipid accumulation at non-toxic concentrations, and was associated
      with the downregulation of several adipocyte-specific transcription factors,
      including peroxisome proliferation-activity receptor gamma (PPARgamma),
      CCAAT/enhancer binding protein (C/EBP)alpha and C/EBPbeta, in a concentration
      dependent manner. Furthermore, it was observed that EEZS markedly inactivated the
      extracellular signal-regulated protein kinase (ERK) and phosphatidylinositide 3
      kinase (PI3K)/Akt pathways, which act upstream of PPARgamma and C/EBPs in
      adipogenesis. These results suggested that EEZS inhibited lipid accumulation by
      downregulating the major transcription factors involved in the pathway of
      adipogenesis, including PPARgamma, C/EBPalpha and C/EBPbeta, via regulation of
      the ERK and PI3K/Akt signaling pathways in 3T3-L1 adipocyte differentiation. This
      indicated the potential use of EEZS as an anti-obesity agent.

PMID- 25760759
TI  - Processing method and corn cultivar affected anthocyanin concentration from dried
      distillers grains with solubles.
AB  - Anthocyanins are water-soluble pigments with health benefits and potential use as
      food colorants. The objectives of this work were to (1) determine optimum
      parameters for the extraction of anthocyanins from dried distillers grain with
      solubles (DDGS), (2) develop a method of anthocyanin extraction from DDGS, (3)
      quantify and identify the extracted anthocyanins, and (4) determine the effect of
      processing methods and corn cultivars on anthocyanin concentration. DDGS samples
      were prepared from purple (PC) and dark (DC) corn and processed using
      conventional enzymes (C) and granular starch hydrolyzing enzymes (GC). Three
      independent variables (ethanol concentration (0, 12.5, and 25%); liquid-to-solid
      ratio (30:1, 40:1, 50:1 mL/g); and extraction temperature (4, 22, and 40  degrees
      C)) and two dependent variables (anthocyanin concentration and a-value (redness))
      were used. Results showed that dark corn DDGS gave anthocyanin concentration
      higher than that of purple corn. The GC process showed total anthocyanin
      concentration higher than that of the conventional method of DDGS production. The
      maximum anthocyanin concentration was obtained at 12.5% ethanol, 40:1 liquid-to
      solid ratio, and 22  degrees C for C-PC [321.0 +/- 37.3 MUg cyanidin-3 glucoside
      (C3G) equivalent/g DDGS]. For GC-PC, 25% ethanol, 30:1 liquid-to-solid ratio, and
      22  degrees C gave 741.4 +/- 12.8 MUg C3G equivalent/g DDGS. For GC-DC, 12.5%
      ethanol, 40:1 liquid-to-solid ratio, and 40  degrees C extraction gave 1573.4 +/-
      84.0 MUg C3G equivalent/g DDGS. LC/MS-MS analysis showed that the major
      anthocyanins were cyanidin-3-glucoside, cyanidin-3-(6"-malonyl) glucoside, and
      peonidin-3-(6"malonyl) glucoside. In conclusion, anthocyanin extraction from
      colored corn DDGS can be optimized using 12.5% ethanol, 40:1 mL/g ratio, and 22 
      degrees C.

PMID- 25760760
TI  - Characterization of sleep breathing pattern in patients with type 2 diabetes:
      sweet sleep study.
AB  - BACKGROUND: Although sleep apnea-hypopnea syndrome (SAHS) is highly prevalent in
      patients with type 2 diabetes (T2D), it is unknown whether or not subjects with
      and without T2D share the same sleep breathing pattern. METHODOLOGY/PRINCIPAL
      FINDINGS: A cross-sectional study in patients with SAHS according to the presence
      (n = 132) or not (n = 264) of T2D. Both groups were matched by age, gender, BMI,
      and waist and neck circumferences. A subgroup of 125 subjects was also matched by
      AHI. The exclusion criteria included chronic respiratory disease, alcohol abuse,
      use of sedatives, and heart failure. A higher apnea hypopnea index (AHI) was
      observed in T2D patients [32.2 (10.2-114.0) vs. 25.6 (10.2-123.4) events/hours; p
      = 0.002). When sleep events were evaluated separately, patients with T2D showed a
      significant increase in apnea events [8.4 (0.1-87.7) vs. 6.3 (0.0-105.6) e/h; p =
      0.044), as well as a two-fold increase in the percentage of time spent with
      oxygen saturation <90% [15.7 (0.0-97.0) vs. 7.9 (0.0-95.6) %; <0.001)], higher
      rates of oxygen desaturation events, and also higher daily sleepiness [7.0 (0.0
      21.0) vs. 5.0 (0.0-21.0); p = 0.006)] than subjects without T2D. Significant
      positive correlations between fasting plasma glucose and AHI, the apnea events,
      and CT90 were observed. Finally, multiple linear regression analyses showed that
      T2D was independently associated with AHI (R2 = 0.217), the apnea index (R2 =
      0.194), CT90 (R2 = 0.222), and desaturation events. CONCLUSIONS/SIGNIFICANCE: T2D
      patients present a different pattern of sleep breathing than subject without
      diabetes. The most important differences are the severity of hypoxemia and the
      number of apneas whereas the incidence of hypopnea episodes is similar.

PMID- 25760761
TI  - Semimechanistic model to characterize nonlinear pharmacokinetics of nimotuzumab
      in patients with advanced breast cancer.
AB  - This study aimed (1) to develop a semimechanistic pharmacokinetic (PK) model for
      nimotuzumab in patients with advanced breast cancer and (2) to identify
      demographic, biochemical, and clinical predictive factors of the PK variability.
      Data from a phase 1 study were analyzed using the nonlinear mixed-effects
      approach (NONMEM). A target-mediated disposition model that included 2 open PK
      compartments, the monoclonal antibody (mAb)-target binding, and target and mAb
      target complex turnovers best described the linear and nonlinear PK. Covariates
      had no influence on the PK parameters. The final parameter estimates were 19.93 L
      (steady-state volume), 0.0045-0.0172 L/h (range of total clearance values), 6.96
      MUg/mL (steady-state binding constant), 5.50 h(-1) (target degradation rate
      constant), 1.43 (MUg/mL) . h(-1) (complex formation rate), and 0.148 h(-1)
      (complex internalization rate constant). The model described the effect of the
      mAb-target binding, and target and mAb-target complex turnovers on nimotuzumab
      PK. Simulations showed that doses above 200 mg maintained the 50% target
      occupancy during all of the treatment. This model can be very useful for knowing
      the dosing schedules required for efficacy and supports further investigation of
      the pharmacokinetic/pharmacodynamic relationships of nimotuzumab to improve its
      therapeutic use.

PMID- 25760762
TI  - Review on triggered liposomal drug delivery with a focus on ultrasound.
AB  - Chemotherapy is widely used for cancer treatment; however, it causes unwanted
      side effects in patients. To avoid these adverse effects, nanocarriers have been
      developed, which can be loaded with the chemotherapeutic agents, directed to the
      cancer site and, once there, are exposed to stimuli that will trigger the drug
      release. Liposomes can be chemically modified to increase their circulation time,
      their stability, and their sensitivity to specific stimulus. Additionally,
      ligands can be conjugated to their surface, allowing for their specific binding
      to receptors overexpressed on the surface of cancer cells and the subsequent
      internalization via endocytosis. Using a triggering mechanism, including
      temperature, ultrasound, enzymes or a change in pH, the release of the drug is
      controlled and induced inside the cells, hence avoiding drug release in systemic
      circulation, which in turn reduces the undesired side effects of conventional
      chemotherapy. Ultrasound has been widely studied as a drug release trigger from
      liposomes, due to its well-known physics and previous uses in medicine. This
      review focuses on liposome-based drug delivery systems, using different trigger
      mechanisms, with a focus on ultrasound. The physical mechanisms of ultrasound
      release are also investigated and the results of in vitro and in vivo studies are
      summarized. 

PMID- 25760763
TI  - A survey of UK healthcare workers' attitudes on volunteering to help with the
      Ebola outbreak in West Africa.
AB  - OBJECTIVE: To understand the barriers and enablers for UK healthcare workers who
      are considering going to work in the current Ebola outbreak in West Africa, but
      have not yet volunteered. DESIGN: After focus group discussions, and a pilot
      questionnaire, an anonymous survey was conducted using SurveyMonkey to determine
      whether people had considered going to West Africa, what factors might make them
      more or less likely to volunteer, and whether any of these were modifiable
      factors. PARTICIPANTS: The survey was publicised among doctors, nurses,
      laboratory staff and allied health professionals. 3109 people answered the
      survey, of whom 472 (15%) were considering going to work in the epidemic but had
      not yet volunteered. 1791 (57.6%) had not considered going, 704 (22.6%) had
      considered going but decided not to, 53 (1.7%) had volunteered to go and 14
      (0.45%) had already been and worked in the epidemic. RESULTS: For those
      considering going to West Africa, the most important factor preventing them from
      volunteering was a lack of information to help them decide; fear of getting Ebola
      and partners' concerns came next. Uncertainty about their potential role, current
      work commitments and inability to get agreement from their employer were also
      important barriers, whereas clarity over training would be an important enabler.
      In contrast, for those who were not considering going, or who had decided against
      going, family considerations and partner concerns were the most important
      factors. CONCLUSIONS: More UK healthcare workers would volunteer to help tackle
      Ebola in West Africa if there was better information available, including clarity
      about roles, cover arrangements, and training. This could be achieved with a well
      publicised high quality portal of reliable information.

PMID- 25760764
TI  - Scheduling scaffolding: the extent and arrangement of assistance during training
      impacts test performance.
AB  - Various kinds of assistance, including prompts, worked examples, direct
      instruction, and modeling, are widely provided to learners across educational and
      training programs. Yet, the effectiveness of assistance during training on long
      term learning is widely debated. The authors examined how the extent and schedule
      of assistance during training on a novel mouse movement task impacted unassisted
      test performance. Learners received different schedules of assistance during
      training, including constant assistance, no assistance, probabilistic assistance,
      alternating assistance, and faded assistance. Constant assistance led to better
      performance during training than no assistance. However, constant assistance
      during training resulted in the worst unassisted test performance. Faded
      assistance during training resulted in the best test performance. This suggests
      that fading may allow learners to create an internal model of the assistance
      without depending on the assistance in a manner that impedes successful transfer
      to unassisted circumstances. 

PMID- 25760765
TI  - Development of a conceptual framework of health-related quality of life in
      locally recurrent rectal cancer.
AB  - AIM: The surgical management of locally recurrent rectal cancer (LRRC) has become
      widely accepted to afford cure and improve quality of life in this subset of
      patients. Thus far, traditional surgical and oncological markers have been used
      to highlight the success of surgical intervention. The use of patient-reported
      outcomes, specifically health-related quality of life (HRQoL), is sparse in these
      patients. This may be in part due to the lack of well-designed, validated
      instruments. This study identifies HRQoL issues relevant to patients undergoing
      surgery for LRRC, with the aim of developing a conceptual framework of HRQoL
      specific to LRRC to enable measurement of patient-reported outcomes in this
      cohort of patients. METHOD: Qualitative focus groups were undertaken at two
      institutions to identify relevant HRQoL themes. The principles of thematic
      content analysis were used to analysis data. NViVo10 was used to analyse data.
      RESULTS: Twenty-one patients participated in six consecutive focus groups. Two
      patterns of themes emerged related to HRQoL and healthcare service delivery and
      utilization. Identified themes related to HRQoL included symptoms, sexual
      function, psychological impact, role and social functioning and future
      perspective. Under healthcare service and delivery and utilization the subdomain
      of disease management, treatment expectations and healthcare professionals were
      identified. CONCLUSION: This is the first qualitative study undertaken
      exclusively in patients with LRRC to ascertain relevant HRQoL outcomes. The
      impact of LRRC on patients is wide-ranging and extends beyond traditional HRQoL
      outcomes. The study operationalizes the identified outcomes into a conceptual
      framework, which will provide the basis for the development of a LRRC-specific
      patient-reported outcome measure.

PMID- 25760768
TI  - C-type lectin-like molecule-1 (CLL1)-targeted TRAIL augments the tumoricidal
      activity of granulocytes and potentiates therapeutic antibody-dependent cell
      mediated cytotoxicity.
AB  - The therapeutic effect of anti-cancer monoclonal antibodies stems from their
      capacity to opsonize targeted cancer cells with subsequent phagocytic removal,
      induction of antibody-dependent cell-mediated cytotoxicity (ADCC) or induction of
      complement-mediated cytotoxicity (CDC). The major immune effector cells involved
      in these processes are natural killer (NK) cells and granulocytes. The latter and
      most prevalent blood cell population contributes to phagocytosis, but is not
      effective in inducing ADCC. Here, we report that targeted delivery of the
      tumoricidal protein tumor necrosis factor-related apoptosis-inducing ligand
      (TRAIL) to granulocyte marker C-type lectin-like molecule-1 (CLL1), using fusion
      protein CLL1:TRAIL, equips granulocytes with high levels of TRAIL. Upon CLL1
      selective binding of this fusion protein, granulocytes acquire additional TRAIL
      mediated cytotoxic activity that, importantly, potentiates antibody-mediated
      cytotoxicity of clinically used therapeutic antibodies (e.g., rituximab,
      cetuximab). Thus, CLL1:TRAIL could be used as an adjuvant to optimize the
      clinical potential of anticancer antibody therapy by augmenting tumoricidal
      activity of granulocytes. 

PMID- 25760769
TI  - Aggregation risk prediction for antibodies and its application to biotherapeutic
      development.
AB  - Aggregation is a common problem affecting biopharmaceutical development that can
      have a significant effect on the quality of the product, as well as the safety to
      patients, particularly because of the increased risk of immune reactions. Here,
      we describe a new high-throughput screening algorithm developed to classify
      antibody molecules based on their propensity to aggregate. The tool, constructed
      and validated on experimental aggregation data for over 500 antibodies, is able
      to discern molecules with a high aggregation propensity as defined by
      experimental criteria relevant to bioprocessing and manufacturing of these
      molecules. Furthermore, we show how this tool can be combined with other
      computational approaches during early drug development to select molecules with
      reduced risk of aggregation and optimal developability properties. 

PMID- 25760767
TI  - Antibody-mediated phagocytosis contributes to the anti-tumor activity of the
      therapeutic antibody daratumumab in lymphoma and multiple myeloma.
AB  - Daratumumab (DARA) is a human CD38-specific IgG1 antibody that is in clinical
      development for the treatment of multiple myeloma (MM). The potential for IgG1
      antibodies to induce macrophage-mediated phagocytosis, in combination with the
      known presence of macrophages in the tumor microenvironment in MM and other
      hematological tumors, led us to investigate the contribution of antibody
      dependent, macrophage-mediated phagocytosis to DARA's mechanism of action. Live
      cell imaging revealed that DARA efficiently induced macrophage-mediated
      phagocytosis, in which individual macrophages rapidly and sequentially engulfed
      multiple tumor cells. DARA-dependent phagocytosis by mouse and human macrophages
      was also observed in an in vitro flow cytometry assay, using a range of MM and
      Burkitt's lymphoma cell lines. Phagocytosis contributed to DARA's anti-tumor
      activity in vivo, in both a subcutaneous and an intravenous leukemic xenograft
      mouse model. Finally, DARA was shown to induce macrophage-mediated phagocytosis
      of MM cells isolated from 11 of 12 MM patients that showed variable levels of
      CD38 expression. In summary, we demonstrate that phagocytosis is a fast, potent
      and clinically relevant mechanism of action that may contribute to the
      therapeutic activity of DARA in multiple myeloma and potentially other
      hematological tumors. 

PMID- 25760771
TI  - Effect of support on metathesis of n-decane: drastic improvement in alkane
      metathesis with WMe5 linked to silica-alumina.
AB  - [WMe6 ] (1) supported on the surface of SiO2 -Al2 O3(500) (2) has been
      extensively characterized by solid-state NMR spectroscopy, elemental analysis,
      and gas quantification, which clearly reveal the formation of a mixture of
      monopodal and bipodal species with the migration of methyl from W to Al. The
      supported species SiO2 -Al2 O3(500) (2) transformed at 120  degrees C into two
      types of carbynic centers, one of which is cationic and the other neutral. These
      species are very efficient for the metathesis of n-decane. Comparison with
      already-synthesized neutral bipodal tungsten indicates that the high increase in
      activity is due to the cationic character of the grafted tungsten. 

PMID- 25760770
TI  - Phage display-based generation of novel internalizing antibody fragments for
      immunotoxin-based treatment of acute myeloid leukemia.
AB  - The current standard treatment for acute myeloid leukemia (AML) is chemotherapy
      based on cytarabine and daunorubicine (7 + 3), but it discriminates poorly
      between malignant and benign cells. Dose-limiting off-target effects and
      intrinsic drug resistance result in the inefficient eradication of leukemic blast
      cells and their survival beyond remission. This minimal residual disease is the
      major cause of relapse and is responsible for a 5-year survival rate of only 24%.
      More specific and efficient approaches are therefore required to eradicate
      malignant cells while leaving healthy cells unaffected. In this study, we
      generated scFv antibodies that bind specifically to the surface of AML blast
      cells and AML bone marrow biopsy specimens. We isolated the antibodies by phage
      display, using subtractive whole-cell panning with AML M2-derived Kasumi-1 cells.
      By selecting for internalizing scFv antibody fragments, we focused on potentially
      novel agents for intracellular drug delivery and tumor modulation. Two
      independent methods showed that 4 binders were internalized by Kasumi-1 cells.
      Furthermore, we observed the AML-selective inhibition of cell proliferation and
      the induction of apoptosis by a recombinant immunotoxin comprising one scFv fused
      to a truncated form of Pseudomonas exotoxin A (ETA'). This method may therefore
      be useful for the selection of novel disease-specific internalizing antibody
      fragments, providing a novel immunotherapeutic strategy for the treatment of AML
      patients. 

PMID- 25760773
TI  - Mobile app rating scale: a new tool for assessing the quality of health mobile
      apps.
AB  - BACKGROUND: The use of mobile apps for health and well being promotion has grown
      exponentially in recent years. Yet, there is currently no app-quality assessment
      tool beyond "star"-ratings. OBJECTIVE: The objective of this study was to develop
      a reliable, multidimensional measure for trialling, classifying, and rating the
      quality of mobile health apps. METHODS: A literature search was conducted to
      identify articles containing explicit Web or app quality rating criteria
      published between January 2000 and January 2013. Existing criteria for the
      assessment of app quality were categorized by an expert panel to develop the new
      Mobile App Rating Scale (MARS) subscales, items, descriptors, and anchors. There
      were sixty well being apps that were randomly selected using an iTunes search for
      MARS rating. There were ten that were used to pilot the rating procedure, and the
      remaining 50 provided data on interrater reliability. RESULTS: There were 372
      explicit criteria for assessing Web or app quality that were extracted from 25
      published papers, conference proceedings, and Internet resources. There were five
      broad categories of criteria that were identified including four objective
      quality scales: engagement, functionality, aesthetics, and information quality;
      and one subjective quality scale; which were refined into the 23-item MARS. The
      MARS demonstrated excellent internal consistency (alpha = .90) and interrater
      reliability intraclass correlation coefficient (ICC = .79). CONCLUSIONS: The MARS
      is a simple, objective, and reliable tool for classifying and assessing the
      quality of mobile health apps. It can also be used to provide a checklist for the
      design and development of new high quality health apps.

PMID- 25760772
TI  - A highly accurate inclusive cancer screening test using Caenorhabditis elegans
      scent detection.
AB  - Early detection and treatment are of vital importance to the successful
      eradication of various cancers, and development of economical and non-invasive
      novel cancer screening systems is critical. Previous reports using canine scent
      detection demonstrated the existence of cancer-specific odours. However, it is
      difficult to introduce canine scent recognition into clinical practice because of
      the need to maintain accuracy. In this study, we developed a Nematode Scent
      Detection Test (NSDT) using Caenorhabditis elegans to provide a novel highly
      accurate cancer detection system that is economical, painless, rapid and
      convenient. We demonstrated wild-type C. elegans displayed attractive chemotaxis
      towards human cancer cell secretions, cancer tissues and urine from cancer
      patients but avoided control urine; in parallel, the response of the olfactory
      neurons of C. elegans to the urine from cancer patients was significantly
      stronger than to control urine. In contrast, G protein alpha mutants and
      olfactory neurons-ablated animals were not attracted to cancer patient urine,
      suggesting that C. elegans senses odours in urine. We tested 242 samples to
      measure the performance of the NSDT, and found the sensitivity was 95.8%; this is
      markedly higher than that of other existing tumour markers. Furthermore, the
      specificity was 95.0%. Importantly, this test was able to diagnose various cancer
      types tested at the early stage (stage 0 or 1). To conclude, C. elegans scent
      based analyses might provide a new strategy to detect and study disease
      associated scents. 

PMID- 25760774
TI  - Demethoxycurcumin-carrying chitosan-antibody core-shell nanoparticles with
      multitherapeutic efficacy toward malignant A549 lung tumor: from in vitro
      characterization to in vivo evaluation.
AB  - Targeting controlled release core-shell nanocarriers with the potential to
      overcome multidrug resistant (MDR) lung cancer were prepared based on
      demethoxycurcumin (DMC) loaded amphiphilic chitosan nanoparticles coated with an
      anti-EGFR antibody layer. The nanocarriers were characterized with regard to size
      with dynamic light scattering, SEM, and TEM. The characterization confirmed the
      nanocarriers to have a surface coating of the anti-EGFR antibody and a final size
      excellently suited for circulating targeting nanocarriers, i.e., <200 nm in
      diameter. In vitro drug release revealed extended quasi-Fickian release from the
      nanocarriers, with the anti-EGFR layer further reducing the release rate. Cell
      culture experiments using normoxic and MDR hypoxic cells overexpressing EGFR
      confirmed improved DMC delivery for anti-EGFR coated particles and revealed that
      the DMC was delivered to the cytoplasmic region of the cells, forming
      nanoprecipitates in lysosomes and endosomes. The effective endocytosis and
      targeting of the core-shell nanoparticles resulted in the nanocarriers achieving
      high cytotoxicity also against MDR cells. The therapeutic potential was further
      confirmed in an A549 xenograft lung tumor mouse model, where DMC loaded core
      shell nanocarriers achieved about 8-fold reduction in tumor volume compared with
      control group over the 8 weeks of the investigation. Both in vitro and in vivo
      data suggest the anti-EGFR coated core-shell nanocarriers as highly promising for
      treatment of hypoxic MDR cancers, especially for non-small cell lung cancer. 

PMID- 25760775
TI  - Chromosome constitution and origin analysis in three derivatives of Triticum
      aestivum--Leymus mollis by molecular cytogenetic identification.
AB  - Leymus mollis (2n = 4x = 28, NsNsXmXm) is an important tetraploid species in
      Leymus (Poaceae: Triticeae) and a useful genetic resource for wheat breeding
      because of the stress tolerance and disease resistance of this species. The
      development of Triticum aestivum (common wheat) - L. mollis derivatives with
      desirable genes will provide valuable bridge materials for wheat improvement,
      especially regarding powdery mildew resistance genes, which are rarely documented
      in L. mollis. In the present study, three derivatives of common wheat cultivar
      7182 and L. mollis, namely M47, M51, and M42, were subjected to chromosomal
      characterization via cytogenetic identification, the analysis of molecular
      markers, and genomic in situ hybridization. These derivatives were all
      morphologically and cytogenetically stable. M47 was highly resistant to powdery
      mildew and nearly immune to stripe rust at the adult stage, and the chromosome
      constitution of this derivative can be expressed as 2n = 56 = 42T.a + 14L.m
      (where T.a = T. aestivum chromosomes; L.m = L. mollis chromosomes). Compared to
      M47, M42 was also resistant to stripe rust but was susceptible to powdery mildew;
      the chromosome constitution of M42 was 2n = 54 = 42T.a + 12L.m, in which a pair
      of homoeologous group 7 L.m chromosomes was eliminated. Finally, M51 was
      susceptible to powdery mildew and stripe rust and had a chromosome constitution
      of 2n = 48 = 42T.a + 6L.m, in which four pairs of L.m chromosomes from
      homoeologous groups 2, 4, 5, and 7 were eliminated. The differing disease
      resistances of the three derivatives are discussed in this report in the context
      of their chromosomal variations; this information can thus contribute to breeding
      disease resistant wheat with the potential for applying these derivatives as
      useful bridge materials. 

PMID- 25760776
TI  - Click-chemistry strategy for labeling antibodies with copper-64 via a cross
      bridged tetraazamacrocyclic chelator scaffold.
AB  - We report a click-chemistry based modular strategy for antibody labeling with
      (64)Cu (t1/2 = 12.7 h; beta(+) 0.656 MeV, 17.4%; beta(-) 0.573 MeV, 39%; EC 43%)
      under ambient condition utilizing a cross-bridged tetraazamacrocyclic (CB-TE2A)
      analogue, which otherwise requires harsh conditions that make the CB-TE2A
      analogues under-utilized for protein labeling despite the fact that they form
      kinetically inert copper complexes with high in vivo stability. Our strategy
      involves prelabeling a CB-TE2A based scaffold (CB-TE2A-1C) with (64)Cu and its
      subsequent reaction with an antibody via the tetrazine-norbornene mediated click
      chemistry. The effectiveness of this strategy was demonstrated by labeling two
      monoclonal antibodies, an anti-PSMA antibody (YPSMA-1) and a chimeric anti
      phosphatidylserine antibody (Bavituximab). The immunoreactivity of the antibodies
      remained unchanged after the tetrazine modification and click-chemistry (64)Cu
      labeling. To further demonstrate the practicality of the modular (64)Cu labeling
      strategy, we tested positron emission tomography (PET) imaging of tumor with the
      (64)Cu-labeled bavituximab in a mouse xenograft model. The tumor visualization
      and uptake of the labeled antibody exhibited the versatility of the click
      chemistry strategy. 

PMID- 25760777
TI  - Reversal of the importance of steric and electronic effects in the base-promoted
      alpha-silylation of sulfides.
AB  - Lithiation of alpha-C-H groups in organic substrates by RLi or R2NLi followed by
      silylation with R'3SiCl generally provides analogous products regardless of the
      R' group of R'3SiCl. A striking exception using 3,4-benzothiophane as substrate
      depending on whether R' is methyl, phenyl, or isopropyl is demonstrated. With R'
      = Me or Ph, the geminal alpha,alpha-bis-silylated products result whereas with i
      Pr3SiCl the trans-alpha,alpha'-bis-silylated sulfide is formed. The latter
      pathway provides ready access to the C2-symmetric enantiomers of trans-2,5
      bis(triisopropylsilyl)-3,4-benzothiophane. 

PMID- 25760781
TI  - Intermolecular asymmetric carboesterification of alkenes by using chiral amine
      auxiliaries under O2: synthesis of enantioenriched alpha-methylene-gamma-lactones
      through chloropalladation of alkynes.
AB  - Herein, the first example of chloropalladation-initiated asymmetric
      intermolecular carboesterification of alkenes with alkynes by using chiral amine
      auxiliaries is reported. The use of (1S,2S)-N(1),N(1)-dimethylcyclohexane-1,2
      diamine auxiliaries is essential for providing alpha-methylene-gamma-lactones
      products in moderate to high yields and excellent enantioselectivities at room
      temperature. Moreover, the chiral amine auxiliaries can be readily removed by
      hydrolysis during the reaction process to keep the absolute configuration. This
      oxygen- and water-promoted asymmetric reaction opens a new window to study
      asymmetric processes in halopalladation reactions.

PMID- 25760778
TI  - Myeloperoxidase evokes substantial vasomotor responses in isolated skeletal
      muscle arterioles of the rat.
AB  - AIMS: Myeloperoxidase (MPO) catalyses the formation of a wide variety of
      oxidants, including hypochlorous acid (HOCl), and contributes to cardiovascular
      disease progression. We hypothesized that during its action MPO evokes
      substantial vasomotor responses. METHODS: Following exposure to MPO (1.92 mU mL(
      1)) in the presence of increasing concentrations of hydrogen peroxide (H2O2),
      changes in arteriolar diameter of isolated gracilis skeletal muscle arterioles
      (SMAs) and coronary arterioles (CAs) and in the isometric force in basilar
      arteries (BAs) of the rat were monitored. RESULTS: Myeloperoxidase increased
      vascular tone to different degrees in CAs, SMAs and BAs. The mechanism of
      increased vasoconstriction was studied in detail in SMAs. MPO-evoked
      vasoconstrictions were prevented by the MPO inhibitor 4-aminobenzhydrazide (50
      MUM), by endothelium removal in the SMAs. Surprisingly, the HOCl scavenger L
      methionine (100 MUM), the thromboxane A2 (TXA2) antagonist SQ-29548 (1 MUM) or
      the non-specific cyclooxygenase (COX) antagonist indomethacin (1 MUM) converted
      the MPO-evoked vasoconstrictions to pronounced vasodilations in SMAs, not seen in
      the presence of H2O2. In contrast to noradrenaline-induced vasoconstrictions, the
      MPO-evoked vasoconstrictions were not accompanied by significant increases in
      arteriolar [Ca(2+)] levels in SMAs. CONCLUSION: These data showed that H2O2 
      derived HOCl to be a potent vasoconstrictor upon MPO application. HOCl activated
      the COX pathway, causing the synthesis and release of a TXA2-like substance to
      increase the Ca(2+) sensitivity of the contractile apparatus in vascular smooth
      muscle cells and thereby to augment H2 O2 -evoked vasoconstrictions.
      Nevertheless, inhibition of the HOCl-COX-TXA2 pathway unmasked the effects of
      additional MPO-derived radicals with a marked vasodilatory potential in SMAs.

PMID- 25760783
TI  - Toward understanding and treating violence in America: some contributions from
      group dynamic and group therapy perspectives: introduction to part II.
AB  - The co-editors of the journal's two special issues on "Violence in America" from
      group psychotherapy and mental health standpoints review the articles in Part I
      and introduce the articles in Part II. The latter includes articles on anger
      management in groups, group psychotherapy for domestic violence, domestic
      "homegrown" terrorism, and two general commentaries. The co-editors provide broad
      reference points for the focus on clinical concerns, levels of treatment,
      variations in types of perpetrators, screening for groups, and the group-as-a
      whole, relational, and social contexts of violence. Whether in small therapy
      groups, social interventions, or society's management of violence, empathy,
      boundaries, holding, and containment must be provided in such a way that they
      prevent violent acts while healing the hurts and shame that underlie violence in
      all its forms. Therapists' familiarity with these issues in their work can
      contribute fruitfully to treatment efforts and addressing a pressing social
      problem. 

PMID- 25760782
TI  - Residential exposure to estrogen disrupting hazardous air pollutants and breast
      cancer risk: the California Teachers Study.
AB  - BACKGROUND: Some studies show increased breast cancer risk from exposure to
      xenoestrogens, but few have explored exposures via ambient air, which could
      impact large populations. OBJECTIVES: This study explored the association between
      breast cancer risk and residential exposures to ambient estrogen disruptors among
      participants in a large cohort study, the California Teachers Study. METHODS:
      Participants consisted of 112,379 women free of breast cancer and living at a
      California address in 1995/1996. Eleven hazardous air pollutants from the US
      Environmental Protection Agency 2002 list were identified as estrogen disruptors
      based on published endocrine disrupting chemical lists and literature review.
      Census-tract estrogen disruptor air concentrations modeled by the US
      Environmental Protection Agency in 2002 were assigned to participants' baseline
      addresses. Cox proportional hazards models were used to estimate hazard ratios
      associated with exposure to each estrogen disruptor and a summary measure of nine
      estrogenic hazardous air pollutants among all participants and selected
      subgroups, adjusting for age, race/birthplace, socioeconomic status, and known
      breast cancer risk factors. RESULTS: Five thousand three hundred sixty-one
      invasive breast cancer cases were identified between 1995 and 2010. No
      associations were found between residential exposure to ambient estrogen
      disruptors and overall breast cancer risk or hormone receptor-positive breast
      cancer risk, nor among targeted subgroups of participants (pre-/peri-menopausal
      women, post-menopausal women, never-smokers, non-movers, and never-smoking non
      movers). However, elevated risks for hormone receptor-negative tumors were
      observed for higher exposure to cadmium compounds and possibly inorganic arsenic
      among never-smoking non-movers. CONCLUSION: Long-term, low-dose exposure to
      ambient cadmium compounds or possibly inorganic arsenic may be a risk factor for
      breast cancer.

PMID- 25760784
TI  - Group process as a mechanism of change in the group treatment of anger and
      aggression.
AB  - Angry reactions can present unique challenges to the process of conducting group
      therapy, especially when providing group treatment to participants who have
      histories of angry or aggressive behavior. This article briefly reviews relevant
      literature and describes a group-based violence reduction training program
      (VRTP). The VRTP conceptualizes anger and aggression from a frustration
      aggression framework and employs treatment derived from research in the area of
      social problem-solving. An emphasis is placed on how fostering group experiences
      consistent with Irving Yalom's classic work on the theory and practice of group
      therapy can reinforce skill acquisition and general treatment responsiveness.
      Management of the group process is a plausible mechanism of change in group
      treatment of anger. We highlight the challenges and benefits of dealing with
      anger-infused communication while ensuring the integrity of the overall group
      process. Case examples are provided for illustration of VRTP. Future research can
      answer important questions about group process and mechanisms of change in group
      based treatments for anger and aggression. 

PMID- 25760785
TI  - Multi-tiered group therapy model to identify and treat the root causes of
      domestic violence: a proposal integrating current social neuroscience findings.
AB  - Domestic violence (DV) is a national public health crisis. The leading treatment
      model, the Duluth Model, has failed to reduce or prevent DV. New models of
      treatment for DV are needed. In this paper, an emphasis is placed on an
      integrated multimodal approach to treating DV, integrating the current
      psychological science on the neurobiology and brain science of human violence
      with recent findings in the neurobiology of group relationships to present a
      treatment program for DV employing a group therapy model. This group therapy
      treatment approach moves away from the treatment of symptoms to the treatment of
      the root causes of violence. The two-tier Duluth model (a community teaching
      model of psychoeducation and court-mandated behavioral therapies for male
      perpetrators) is expanded to include a third tier. This is a psychological
      science-driven model that identifies and treats the root causes of DV using a
      group process and group systems-oriented approach. 

PMID- 25760786
TI  - Terrorism and right-wing extremism: the changing face of terrorism and political
      violence in the 21st century: the virtual community of hatred.
AB  - There are no psychological characteristics or psychopathology that separates
      terrorists from the general population. Rather it is group dynamics, with a
      particular emphasis on collective identity that helps explain terrorist
      psychology. Just as there is a diverse spectrum of terrorisms, so too is there a
      spectrum of terrorist psychologies. Four waves of terrorism can be distinguished:
      the Anarchist wave, associated with labor violence in the United States in the
      late 19th century; the Anti-Colonial wave (nationalist-separatist), with minority
      groups seeking to be liberated from their colonial masters or from the majority
      in their country; the New Left wave (social revolutionary); and now the Religious
      wave. With the communications revolution, a new phenomenon is emerging which may
      presage a fifth wave: lone wolf terrorists who through the Internet are
      radicalized and feel they belong to the virtual community of hatred. A typology
      of lone wolf terrorism is proposed. 

PMID- 25760787
TI  - Commentary on "Toward understanding and treating violence in America: some
      contributions from group dynamic and group therapy perspectives".

PMID- 25760788
TI  - Commentary on "Toward understanding and treating violence in America: some
      contributions from group dynamic and group therapy perspectives".

PMID- 25760789
TI  - A healing herd: benefits of a psychodynamic group approach in treating body
      focused repetitive behaviors.
AB  - Body-focused repetitive behaviors, such as trichotillomania and skin-picking, are
      not well understood in clinical communities. Research and practice with a
      population exhibiting these behaviors have focused almost exclusively on the
      usefulness of cognitive-behavioral therapy in symptom reduction. The author
      specializes in treating patients with body-focused repetitive behaviors and
      suggests that a holistic, psychodynamic model of treatment for this population
      creates possibilities for deeper change. Group therapy can be an important
      component of this work, helping clients to overcome resistance to change,
      ameliorate shame, work through dissociation, and regulate emotions. This process
      is explored in an examination of a psychodynamic therapy group with pickers and
      pullers. 

PMID- 25760790
TI  - A service dog in group.
AB  - Service dogs are sanctioned by the Americans with Disabilities Act as having
      protected rights allowing them to assist owners with disabilities. These dogs are
      appearing with increasing frequency in healthcare settings, and it is important
      for healthcare providers to understand the rules and regulations given to service
      animals and owners. We discuss processes that transpired when a service dog was
      brought into a psychodynamic psychotherapy group. The purpose of this paper is to
      highlight the unintended consequences of the Americans with Disabilities Act of
      2010 as it concerns service dogs and the impact on the group process. Problems
      resulting from the introduction of service dogs into therapy groups should be
      anticipated and explicitly discussed in the course of the group's transactions. 

PMID- 25760791
TI  - The insufficiency of theory: gaining one's voice as a group therapist.

PMID- 25760795
TI  - Activation of C-H and B-H bonds through agostic bonding: an ELF/QTAIM insight.
AB  - Agostic bonding is of paramount importance in C-H bond activation processes. The
      reactivity of the sigma C-H bond thus activated will depend on the nature of the
      metallic center, the nature of the ligand involved in the interaction and co
      ligands, as well as on geometric parameters. Because of their importance in
      organometallic chemistry, a qualitative classification of agostic bonding could
      be very much helpful. Herein we propose descriptors of the agostic character of
      bonding based on the electron localization function (ELF) and Quantum Theory of
      Atoms in Molecules (QTAIM) topological analysis. A set of 31 metallic complexes
      taken, or derived, from the literature was chosen to illustrate our methodology.
      First, some criteria should prove that an interaction between a metallic center
      and a sigma X-H bond can indeed be described as "agostic" bonding. Then, the
      contribution of the metallic center in the protonated agostic basin, in the ELF
      topological description, may be used to evaluate the agostic character of
      bonding. A sigma X-H bond is in agostic interaction with a metal center when the
      protonated X-H basin is a trisynaptic basin with a metal contribution strictly
      larger than the numerical uncertainty, i.e. 0.01 e. In addition, it was shown
      that the weakening of the electron density at the X-Hagostic bond critical point
      with respect to that of X-Hfree well correlates with the lengthening of the
      agostic X-H bond distance as well as with the shift of the vibrational frequency
      associated with the nuX-H stretching mode. Furthermore, the use of a normalized
      parameter that takes into account the total population of the protonated basin,
      allows the comparison of the agostic character of bonding involved in different
      complexes. 

PMID- 25760794
TI  - Influence of drug transporters and stereoselectivity on the brain penetration of
      pioglitazone as a potential medicine against Alzheimer's disease.
AB  - Pioglitazone is currently undergoing clinical trials for treatment of Alzheimer's
      disease (AD). However, poor brain penetration remains an obstacle to development
      of the drug for such intended clinical uses. In this study, we demonstrate that
      the inhibition of P-glycoprotein (P-gp) significantly increases brain penetration
      of pioglitazone, whereas inhibition of breast cancer resistance protein (BCRP)
      has little effect. We also investigate the stereoselectivity of pioglitazone
      uptake in the brain. When mice were dosed with racemic pioglitazone, the
      concentration of (+)-pioglitazone was 46.6% higher than that of (-)-pioglitazone
      in brain tissue and 67.7% lower than that of (-)-pioglitazone in plasma. Dosing
      mice with pure (+)-pioglitazone led to a 76% increase in brain exposure levels
      compared to those from an equivalent dose of racemic pioglitazone. Pure (+)
      pioglitazone was also shown to have comparable amyloid-lowering capabilities to
      the racemic pioglitazone in an in vitro AD model. These results suggest that P-gp
      may act as a stereoselective barrier to prevent pioglitazone entry into the
      brain. Dosing with (+)-pioglitazone instead of the racemic mixture may result in
      higher levels of brain exposure to pioglitazone, thus potentially improving the
      development of pioglitazone treatment of AD. 

PMID- 25760796
TI  - A dry platform for separation of proteins from biomass-containing
      polysaccharides, lignin, and polyphenols.
AB  - License to mill: Proteins were continuously extracted from polysaccharides,
      lignin, and polyphenol by combining ultrafine milling with electrostatic
      separation. Such a fractionation process does not involve any solvent, catalyst,
      or external source of heating. In addition, this dry process is compatible with
      downstream enzymatic reactions, thus opening an attractive route for producing
      valuable chemicals from biomass. 

PMID- 25760797
TI  - Effects of environmental enrichment on blood vessels in the optic tract of
      malnourished rats: A morphological and morphometric analysis.
AB  - OBJECTIVES: This study aimed to compare the effects of environmental enrichment
      in nourished (on a diet containing 16% protein) and malnourished (on a diet
      containing 6% protein) rats during the critical period of brain development,
      specifically focusing on the optic nerve. METHODS: By means of morphologic and
      morphometric assessment of the optic nerve, we analyzed the changes caused by
      diet and stimulation (environmental enrichment) on postnatal day 35, a time point
      ideal for such morphological analysis since developmental processes are
      considered complete at this age. RESULTS: Malnourished animals presented low body
      and brain weights and high body-to-brain weight ratio compared to well-nourished
      rats. Furthermore, malnourished animals showed morphological changes in the optic
      nerve such as edema and vacuolization characterized by increased interstitial
      space. The malnourished-stimulated group presented lesions characteristic of
      early protein malnutrition but were milder than lesions exhibited by malnourished
      non-stimulated group. The morphometric analysis revealed no difference in glial
      cell density between groups, but there was significantly higher blood vessel
      density in the stimulated rats, independent of their nutritional condition.
      DISCUSSION: Our data indicate that protein malnutrition imposed during the
      critical period of brain development alters the cytoarchitecture of the optic
      nerve. In addition, we affirm that a 1-hour exposure to an enriched environment
      everyday was sufficient for tissue preservation in rats maintained on a low
      protein diet. This protective effect might be related to angiogenesis, as
      confirmed by the increased vascular density observed in morphometric analyses.

PMID- 25760798
TI  - Correction: A novel Prins cascade process for the stereoselective synthesis of
      oxa-bicycles.

PMID- 25760799
TI  - Active Thermochemical Tables: Sequential Bond Dissociation Enthalpies of Methane,
      Ethane, and Methanol and the Related Thermochemistry.
AB  - Active Thermochemical Tables (ATcT) thermochemistry for the sequential bond
      dissociations of methane, ethane, and methanol systems were obtained by analyzing
      and solving a very large thermochemical network (TN). Values for all possible C
      H, C-C, C-O, and O-H bond dissociation enthalpies at 298.15 K (BDE298) and bond
      dissociation energies at 0 K (D0) are presented. The corresponding ATcT standard
      gas-phase enthalpies of formation of the resulting CHn, n = 4-0 species (methane,
      methyl, methylene, methylidyne, and carbon atom), C2Hn, n = 6-0 species (ethane,
      ethyl, ethylene, ethylidene, vinyl, ethylidyne, acetylene, vinylidene, ethynyl,
      and ethynylene), and COHn, n = 4-0 species (methanol, hydroxymethyl, methoxy,
      formaldehyde, hydroxymethylene, formyl, isoformyl, and carbon monoxide) are also
      presented. The ATcT thermochemistry of carbon dioxide, water, hydroxyl, and
      carbon, oxygen, and hydrogen atoms is also included, together with the sequential
      BDEs of CO2 and H2O. The provenances of the ATcT enthalpies of formation, which
      are quite distributed and involve a large number of relevant determinations, are
      analyzed by variance decomposition and discussed in terms of principal
      contributions. The underlying reasons for periodic appearances of remarkably low
      and/or unusually high BDEs, alternating along the dissociation sequences, are
      analyzed and quantitatively rationalized. The present ATcT results are the most
      accurate thermochemical values currently available for these species. 

PMID- 25760800
TI  - Paris saponin II inhibits human ovarian cancer cell-induced angiogenesis by
      modulating NF-kappaB signaling.
AB  - The clinical applications of Rhizoma paridis in traditional Chinese medicine are
      well known. However, the therapeutic potential of Rhizoma paridis and its active
      component such as Paris saponin I (polyphyllin D) and Paris saponin II (PSII)
      (formosanin C) in cancer treatments have not yet been fully explored. Recent
      studies have demonstrated that PSII and chemoagents exhibit comparable inhibitory
      affects against human ovarian cancer cell growth. Since NF-kappaB, a ubiquitous
      transcription factor that plays an important role in cancer biology, is often
      associated with gynecological cancers, in the present study, we evaluated the
      possibility that PSII modulates NF-kappaB activity and VEGF-mediated angiogenesis
      and elucidated the molecular mechanisms underlying such effects. We assessed the
      effects of PSII on NF-kappaB activity in SKOV3 tumor cells and on tumor cell
      induced-angiogenesis using standardized angiogenesis in vitro, ex vivo and in
      vivo assays, western blot analysis and kinase assay. We also assessed the effect
      of the super-engineered repressor of IKBalpha and its effect, in combination with
      PSII treatment on tumor growth and angiogenesis in xenograft athymic mouse models
      of ovarian cancer (SKOV3 and SKOV3/mutant IKBalpha cells) using color Doppler
      ultrasound and traditional immunohistochemistry. We showed that PSII suppressed
      NF-kappaB activation as a result of the reduction in IKKbeta kinase activity on
      its substrate IkappaBalpha and the expression of IKKbeta. Compromising NF-kappaB
      activation reduced the expression of NF-kappaB-downstream targets such as VEGF,
      Bcl-2 and Bcl-xL. Such inhibitory effects at molecular levels appear to
      compromise tumor growth and angiogenesis. Most importantly, the combination of
      PSII treatment and constitutive repression of IKBalpha activity exhibited marked
      inhibitory effects against human ovarian cancer cell growth in a xenograft mouse
      model of ovarian cancer. For the first time, we provide evidence showing that
      PSII potently inhibits angiogenesis and the growth of human ovarian cancer by
      suppressing NF-kappaB signaling. 

PMID- 25760801
TI  - A facile and universal top-down method for preparation of monodisperse transition
      metal dichalcogenide nanodots.
AB  - Despite unique properties of layered transition-metal dichalcogenide (TMD)
      nanosheets, there is still lack of a facile and general strategy for the
      preparation of TMD nanodots (NDs). Reported herein is the preparation of a series
      of TMD NDs, including TMD quantum dots (e.g. MoS2 , WS2 , ReS2 , TaS2 , MoSe2 and
      WSe2 ) and NbSe2 NDs, from their bulk crystals by using a combination of grinding
      and sonication techniques. These NDs could be easily separated from the N-methyl
      2-pyrrolidone when post-treated with n-hexane and then chloroform. All the TMD
      NDs with sizes of less than 10 nm show a narrow size distribution with high
      dispersity in solution. As a proof-of-concept application, memory devices using
      TMD NDs, for example, MoSe2 , WS2 , or NbSe2 , mixed with polyvinylpyrrolidone as
      active layers, have been fabricated, which exhibit a nonvolatile write-once-read
      many behavior. These high-quality TMD NDs should have various applications in
      optoelectronics, solar cells, catalysis, and biomedicine. 

PMID- 25760802
TI  - Fabrication of Large Size Ex Vivo-Produced Oral Mucosal Equivalents for Clinical
      Application.
AB  - The soft tissue reconstruction of significant avulsed and/or surgically created
      tissue defects requires the ability to manufacture substantial soft tissue
      constructs for repair of the resulting wounds. In this study, we detail the
      issues that need to be addressed in upsizing the manufacture of larger tissue
      engineered devices (ex vivo-produced oral mucosa equivalent [EVPOME]) in vitro
      from a methodology previously used for smaller constructs. The larger-sized
      EVPOME, consisting of autologous human oral keratinocytes and a dermal
      substitute, AlloDerm((r)), was fabricated for the purpose of reconstructing large
      clinical defects. Regulated as an autologous somatic cell therapy product, the
      fabrication process abided by current Good Manufacturing Practices and current
      Good Tissue Practices as required by the Center for Biologics Evaluation and
      Research (CBER) of the United States Food and Drug Administration (FDA).
      Successful fabrication of large EVPOMEs utilized a higher cell seeding density
      (5.3*10(5) cells/cm(2)) with a relatively thinner AlloDerm, ranging from 356.6 to
      508.0 MUm in thickness. During the air-liquid interface culture, the thickness of
      the scaffold affected the medium diffusion rate, which, in turn, resulted in
      changes of epithelial stratification. Histologically, keratinocyte progenitor
      (p63), proliferation (Ki-67), and late differentiation marker (filaggrin)
      expression showed differences correlating with the expression of glucose
      transporter-1 (GLUT1) in the EVPOMEs from the thickest (550-1020 MUm) to the
      thinnest (228.6-330.2 MUm) AlloDerm scaffold. Glucose consumption and 2
      deoxyglucose (2DG) uptake showed direct correlation with scaffold thickness. The
      scaffold size and thickness have an impact on the cellular phenotype and
      epithelial maturation in the manufacturing process of the EVPOME due to the
      glucose accessibility influenced by the diffusion rate. These outcomes provide
      basic strategies to manufacture a large-sized, healthy EVPOME graft for
      reconstructing large mucosa defects.

PMID- 25760803
TI  - A novel endoglin mutation in hereditary hemorrhagic telangiectasia type 1: a case
      report.
AB  - Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant disorder
      characterized by aberrant vascular development. Mutations in two genes, endoglin
      (ENG) and activin receptor-like kinase 1 (ACVRL1) are associated with HHT. The
      present case study revealed the molecular diagnosis in a family exhibiting the
      clinical features of HHT disease. The coding exon and flanking intronic regions
      of the ENG and ACVRL1 genes were sequenced and a novel mutation in exon 10 of ENG
      was observed in the family. The mutation (c.1426C>T) in exon 10 of the ENG gene
      caused a G476X mutation, which results in a premature stop codon and a truncated
      ENG protein. This finding demonstrated a novel mutation in the ENG gene in a
      Chinese family, which suggested that a truncated ENG protein may cause HHT. The
      present study established a genetic test to confirm the clinical diagnosis in
      individuals and provide an opportunity for early detection and management of the
      disease.

PMID- 25760804
TI  - Naltrexone vs Placebo for the Treatment of Alcohol Dependence: A Randomized
      Clinical Trial.
AB  - IMPORTANCE: Alcohol use disorder is one of the leading causes of disability
      worldwide. While effective pharmacological treatments exist, they are efficacious
      only in certain individuals, contributing to their limited use. Secondary
      analysis of clinical trial data suggests that a functional polymorphism
      (rs1799971, Asn40Asp) of the u-opioid receptor gene (OPRM1) is associated with
      the risk of relapse to heavy drinking following treatment with the opioid
      antagonist naltrexone. OBJECTIVE: To prospectively examine whether rs1799971 is
      predictive of naltrexone treatment response. DESIGN, SETTING, AND PARTICIPANTS:
      We conducted a 12-week, double-blind, randomized clinical trial of naltrexone vs
      placebo in individuals with alcohol dependence (intent-to-treat analysis).
      Participants were randomly assigned to study treatment based on the presence of 1
      or 2 copies of the Asp40 allele compared with those homozygous for the Asn40
      allele (2 * 2 cell design). Recruitment occurred between January 2009 and
      September 2013. All participants were seen in an outpatient clinical setting. A
      convenience sample of participants (n = 221) was recruited from 5 sites. All
      participants met DSM-IV criteria for alcohol dependence, with no concurrent
      psychotic or manic symptoms, no use of concurrent psychotropic medications, and
      no current dependence on illicit substances. INTERVENTIONS: The study drug was
      naltrexone (50 mg) given once daily or corresponding placebo. MAIN OUTCOMES AND
      MEASURES: The primary study outcome measure was relapse to heavy drinking
      measured using the timeline follow-back method. RESULTS: There was no evidence of
      a genotype * treatment interaction on the primary outcome of heavy drinking (P =
      .32). In the Asn40 group, the observed effect of naltrexone was similar to that
      in previous trials (odds ratio, 0.69; 95% CI, 0.41-1.18; P = .17), with a very
      small naltrexone effect in the Asp40 group (odds ratio, 1.10; 95% CI, 0.52-2.31;
      P = .80), contrary to the pattern expected a priori. A significant reduction in
      heavy drinking occurred across all groups (P = .001). Other drinking outcomes,
      and all secondary outcomes, demonstrated similar time effects, with no genotype *
      treatment interaction. CONCLUSIONS AND RELEVANCE: The results of this study do
      not support the hypothesis that the Asp40 allele moderates the response to
      naltrexone treatment. It is premature to use the Asn40Asp polymorphism as a
      biomarker to predict the response to naltrexone treatment of alcohol dependence.
      TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00831272.

PMID- 25760805
TI  - The role of isomerization in the kinetics of self-assembly: p-terphenyl-m
      dicarbonitrile on the Ag(111) surface.
AB  - Using a toolkit of theoretical techniques comprising ab initio density functional
      theory calculations, the nudged elastic band method and kinetic Monte Carlo (KMC)
      modeling, we investigate in great detail how para-terphenyl-meta-dicarbonitrile
      (pTmDC) molecules diffuse and isomerize to self-assemble on the Ag(111) surface.
      We show that molecules "walk" on the surface via a pivoting mechanism moving each
      of its two "legs" one at a time. We then identify a peculiar "under-side"
      isomerization mechanism capable of changing the molecules chirality, and
      demonstrate that it is fundamental in understanding the growth of hydrogen
      bonding assembles of ribbons, linkers, clusters and brickwall islands on the
      Ag(111) surface, as observed in recent scanning tunneling microscopy experiments
      (ChemPhysChem, 2010, 11, 1446). The discovered underlying atomistic mechanism of
      self-assembly may be behind the growth of other hydrogen bonding structures of
      chiral molecules on metal surfaces. 

PMID- 25760806
TI  - MoS2 nanosheets as an effective fluorescence quencher for DNA methyltransferase
      activity detection.
AB  - As one of the inorganic graphene analogues, two dimensional MoS2 nanosheets have
      been drawing extensive attention in the past few years due to their remarkable
      structural and electronic properties. Herein, a simple signal-on fluorescence DNA
      methyltransferase (MTase) activity assay using a MoS2 nanosheet mediated
      fluorescence quenching strategy is described. Briefly, substrate DNA is designed
      to possess a double-stranded DNA (ds-DNA) segment containing the recognition
      sequence of DNA adenosine methyltransferase (Dam) and a single-stranded DNA (ss
      DNA) segment for anchoring the substrate DNA to MoS2 nanosheets via van der Waals
      interactions. Once the substrate DNA is absorbed onto MoS2 nanosheets, the
      fluorescence of the fluorophores labeled to the end of the ds-DNA region is
      quenched. When the substrate DNA is methylated by Dam, fluorescence is recovered
      resulting from the release of the fluorophore labeled segment cleaved by the
      methylation sensitive restriction endonuclease DpnI. Since the fluorescence
      recovery directly reflects the methylation level, the Dam MTase activity can be
      quantified accordingly. Based on this assay, a linear range of 0.2-20 U mL(-1) is
      achieved with high sensitivity and selectivity. Furthermore, the inhibitor
      screening ability is well demonstrated. 

PMID- 25760809
TI  - LMP-1 induces survivin expression to inhibit cell apoptosis through the NF-kappaB
      and PI3K/Akt signaling pathways in nasal NK/T-cell lymphoma.
AB  - The latent membrane protein-1 (LMP-1) is essential for Epstein-Barr virus (EBV)
      induced nasal natural killer/T-cell lymphoma (NKTL). The aim of the present study
      was to evaluate the role of LMP-1 in NKTL. Two human EBV-positive NKTL cell lines
      (SNK-6 and SNT-8) were transfected with pcDNA3.1-LMP-1 or LMP-1 siRNA. Compared
      with the blank control, the cell apoptosis rates were decreased by 10.31 and
      12.05% after pcDNA3.1-LMP-1 transfection and increased by 41.48 and 35.63% after
      lentiviral LMP-1 siRNA infection in the SNK-6 and SNT-8 cells. Survivin
      expression was induced by LMP-1, and the effect was attenuated by inhibitors of
      survivin, NF-kappaB and PI3K/Akt. Reduction in cell apoptosis by LMP-1 was also
      inhibited by inhibitors of survivin, NF-kappaB and PI3K/Akt. For the in vivo
      assay, tumor-bearing mice were established by subcutaneous injection with
      differentially treated SNT-8 cells into the back of the nude mice, and the tumor
      growth in the different groups was recorded. The results revealed that tumor
      formation and growth were also inhibited by treatment with survivin, NF-kappaB
      and PI3K/Akt inhibitors. Collectively, LMP-1-induced survivin expression
      inhibited cell apoptosis through the NF-kappaB and PI3K/Akt pathways, and
      survivin may be a new target for the treatment of NKTL induced by EBV. 

PMID- 25760810
TI  - Challenges of minimally invasive pancreas surgery growth with such a high
      learning curve.

PMID- 25760811
TI  - Estimation of the environmental effect of natural volatile organic compounds from
      Chamaecyparis obtusa and their effect on atopic dermatitis-like skin lesions in
      mice.
AB  - Aromatherapy has been suggested as an alternative therapeutic method for the
      treatment of atopic dermatitis (AD), eczema and other skin diseases. In the
      current study, the anti-atopic properties of the volatile organic compounds of
      Chamaecyparis obtusa (VOCCo) were examined to determine whether they are amenable
      for use as a pharmaceutical candidate. The alterations in histological features,
      serum IgE levels and mast cell infiltration following exposure to VOCCo were
      determined in a 2,4-dinitrochlorobenzene (DNCB)-induced AD-like mouse model. The
      results of these experiments demonstrated that VOCCo inhibited the development of
      AD-like skin lesions by reducing the serum IgE level and mast cell infiltration
      into the dermal and subcutaneous layers. This was supported by screening of
      immune cytokine mRNAs, including interleukin (IL)-1beta and IL-6 from the skin of
      DNCB-treated mice. The expression of IL-1beta and IL-6 in the skin lesions of
      mice was dose-dependently inhibited by treatment with VOCCo. Furthermore,
      treatment with VOCCo resulted in the recovery of histopathological features in AD
      like skin lesions. These results suggest that VOCCo may have therapeutic and
      preventive effects for the development of AD.

PMID- 25760812
TI  - Effectiveness of posterior decompression techniques compared with conventional
      laminectomy for lumbar stenosis.
AB  - BACKGROUND: The gold standard treatment for symptomatic lumbar stenosis
      refractory to conservative management is a facet-preserving laminectomy. New
      techniques of posterior decompression have been developed to preserve spinal
      integrity and to minimise tissue damage by limiting bony decompression and
      avoiding removal of the midline structures (i.e. spinous process, vertebral arch
      and interspinous and supraspinous ligaments). OBJECTIVES: To compare the
      effectiveness of techniques of posterior decompression that limit the extent of
      bony decompression or avoid removal of posterior midline structures of the lumbar
      spine versus conventional facet-preserving laminectomy for the treatment of
      patients with degenerative lumbar stenosis. SEARCH METHODS: An experienced
      librarian conducted a comprehensive electronic search of the Cochrane Central
      Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, Web of Science, and the
      clinical trials registries ClinicalTrials.gov and World Health Organization
      International Clinical Trials Registry Platform (WHO ICTRP) for relevant
      literature up to June 2014. SELECTION CRITERIA: We included prospective
      controlled studies comparing conventional facet-preserving laminectomy versus a
      posterior decompressive technique that avoids removal of posterior midline
      structures or a technique involving only partial resection of the vertebral arch.
      We excluded studies describing techniques of decompression by means of
      interspinous process devices or concomitant (instrumented) fusion procedures.
      Participants included individuals with symptomatic degenerative lumbar stenosis
      only. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed
      risk of bias using the Cochrane Back Review Group criteria for randomised
      controlled trials (RCTs) and the Newcastle-Ottawa Scale for non-randomised
      studies. We extracted data regarding demographics, intervention details and
      outcome measures. MAIN RESULTS: A total of four high-quality RCTs and six low
      quality RCTs met the search criteria of this review. These studies included a
      total of 733 participants. Investigators compared three different posterior
      decompression techniques versus conventional laminectomy. Three studies (173
      participants) compared unilateral laminotomy for bilateral decompression versus
      conventional laminectomy. Four studies (382 participants) compared bilateral
      laminotomy versus conventional laminectomy (one study included three treatment
      groups and compared unilateral and bilateral laminotomy vs conventional
      laminectomy). Finally, four studies (218 participants) compared a split-spinous
      process laminotomy versus conventional laminectomy.Evidence of low or very low
      quality suggests that different techniques of posterior decompression and
      conventional laminectomy have similar effects on functional disability and leg
      pain. Only perceived recovery at final follow-up was better in people who
      underwent bilateral laminotomy compared with conventional laminectomy (two RCTs,
      223 participants, odds ratio 5.69, 95% confidence interval (CI) 2.55 to
      12.71).Among the secondary outcome measures, unilateral laminotomy for bilateral
      decompression and bilateral laminotomy resulted in numerically fewer cases of
      iatrogenic instability, although in both cases, the incidence of instability was
      low (three RCTs, 166 participants, odds ratio 0.28, 95% CI 0.07 to 1.15; three
      RCTs, 294 participants, odds ratio 0.10, 95% CI 0.02 to 0.55, respectively). The
      difference in severity of postoperative low back pain following bilateral
      laminotomy (two RCTs, 223 participants, mean difference -0.51, 95% CI -0.80 to 
      0.23) and split-spinous process laminotomy compared with conventional laminectomy
      (two RCTs, 97 participants, mean difference -1.07, 95% CI -2.15 to -0.00) was
      significantly less, but was too small to be clinically important. A quantitative
      comparison between unilateral laminotomy and conventional laminectomy was not
      possible because of different reporting of outcome measures. We found no evidence
      to show that the incidence of complications, length of the procedure, length of
      hospital stay and postoperative walking distance differed between techniques of
      posterior decompression. AUTHORS' CONCLUSIONS: The evidence provided by this
      systematic review for the effects of unilateral laminotomy for bilateral
      decompression, bilateral laminotomy and split-spinous process laminotomy compared
      with conventional laminectomy on functional disability, perceived recovery and
      leg pain is of low or very low quality. Therefore, further research is necessary
      to establish whether these techniques provide a safe and effective alternative
      for conventional laminectomy. Proposed advantages of these techniques regarding
      the incidence of iatrogenic instability and postoperative back pain are
      plausible, but definitive conclusions are limited by poor methodology and poor
      reporting of outcome measures among included studies. Future research is
      necessary to establish the incidence of iatrogenic instability using standardised
      definitions of radiological and clinical instability at comparable follow-up
      intervals. Long-term results with these techniques are currently lacking.

PMID- 25760813
TI  - Treatment of child/adolescent obesity using the addiction model: a smartphone app
      pilot study.
AB  - BACKGROUND: The aim of this study was to test a weight loss program for young
      people based on an addiction treatment approach. METHODS: A pilot study (n=43)
      was conducted of a 20-week child/adolescent obesity intervention based on an
      addiction treatment model (staged, incremental withdrawal from problem foods,
      snacking/grazing, and excessive amounts at meals) and implemented by a server
      integrated smartphone app with health professional support. The primary outcome
      was standardized %overBMI measured at four time points. Secondary outcomes were
      participants' self-ratings of self-esteem, control over food, and the degree they
      turned to food when stressed. User satisfaction data were collected with an
      online questionnaire. Latent growth modeling techniques were used to identify
      independent variables and possible mediating treatment process variables
      associated with weight change. RESULTS: Mean age of participants was 16 years
      (range, 10-21), 65% girls, and 84% Caucasian. Twenty-seven (63%) completed the
      program. There was a significant decrease in %overBMI over time of 7.1. There
      were significant improvements in participant ratings of self-esteem, control over
      food, and a reduction in turning to food when stressed. Males, younger
      participants, and participants with higher levels of program compliance achieved
      better weight loss. Participants who reported that calling obesity an addiction
      made their guilt worse experienced poorer weight loss. Females were more likely
      than males to report "addiction guilt," and this partly mediated the overall
      gender effect. CONCLUSIONS: The staged, incremental food withdrawal approach was
      feasible to implement and was useful in helping reduce excessive weight,
      particularly among boys.

PMID- 25760814
TI  - Exploration of Daphnia behavioral effect profiles induced by a broad range of
      toxicants with different modes of action.
AB  - Behavior is increasingly reported as a sensitive and early indicator of toxicant
      stress in aquatic organisms. However, the systematic understanding of behavioral
      effects and comparisons between effect profiles is hampered because the available
      studies are limited to few chemicals and differ in the exposure conditions and
      effect parameters examined. The aims of the present study were 1) to explore
      behavioral responses of Daphnia magna exposed to different toxicants, 2) to
      compare behavioral effect profiles with regard to chemical modes of action, and
      3) to determine the sensitivity and response time of behavioral parameters in a
      new multi-cell exposure system named Multi-DaphTrack compared with currently
      utilized tests. Twelve compounds covering different modes of toxic action were
      selected to sample a wide range of potential effect profiles. Acute standard
      immobilization tests and 48 h of behavioral tracking were performed in the
      customized Multi-DaphTrack system and a single-cell commercialized biological
      early warning system. Contrasting behavioral profiles were observed for average
      speed (i.e., intensity, time of effect onset, effect duration), but no distinct
      behavioral profiles could be drawn from the chemical mode of action. Most
      compounds tested in the Multi-DaphTrack system induced an early and significant
      average speed increase at concentrations near or below the 10% effective
      concentration (48 h) of the acute immobilization test, demonstrating that the
      Multi-DaphTrack system is fast and sensitive. To conclude, behavior endpoints
      could be used as an alternative or complement to the current acute standard test
      or chemical analysis for the predictive evaluation of ecotoxic effects of
      effluents or water bodies.

PMID- 25760815
TI  - Arabidopsis EF-Tu receptor enhances bacterial disease resistance in transgenic
      wheat.
AB  - Perception of pathogen (or microbe)-associated molecular patterns (PAMPs/MAMPs)
      by pattern recognition receptors (PRRs) is a key component of plant innate
      immunity. The Arabidopsis PRR EF-Tu receptor (EFR) recognizes the bacterial PAMP
      elongation factor Tu (EF-Tu) and its derived peptide elf18. Previous work
      revealed that transgenic expression of AtEFR in Solanaceae confers elf18
      responsiveness and broad-spectrum bacterial disease resistance. In this study, we
      developed a set of bioassays to study the activation of PAMP-triggered immunity
      (PTI) in wheat. We generated transgenic wheat (Triticum aestivum) plants
      expressing AtEFR driven by the constitutive rice actin promoter and tested their
      response to elf18. We show that transgenic expression of AtEFR in wheat confers
      recognition of elf18, as measured by the induction of immune marker genes and
      callose deposition. When challenged with the cereal bacterial pathogen
      Pseudomonas syringae pv. oryzae, transgenic EFR wheat lines had reduced lesion
      size and bacterial multiplication. These results demonstrate that AtEFR can be
      transferred successfully from dicot to monocot species, further revealing that
      immune signalling pathways are conserved across these distant phyla. As novel
      PRRs are identified, their transfer between plant families represents a useful
      strategy for enhancing resistance to pathogens in crops. 

PMID- 25760816
TI  - Vinyl ruthenium-modified biphenyl and 2,2'-bipyridines.
AB  - We report here on ruthenium alkenyl complexes 2 and 3 derived from 2,2'
      bipyridine and their Re(CO)3X adducts 4a,b and 5. Detailed electrochemical
      studies on these complexes and spectroscopic characterization of their oxidized
      forms by IR, UV/vis/NIR, and electron paramagnetic resonance spectroscopies as
      well as quantum chemical studies reveal sizable (bridging) ligand contributions
      to the redox orbitals. Engagement of the free bipy functions of complexes 2 and 3
      in binding to the electron-withdrawing fac-Re(CO)3X (X = Br, Cl) moiety enhances
      the metal-to-ligand charge-transfer character of the optical excitations, causes
      sizable anodic shifts of the redox potentials, and decreases the number of
      observable anodic redox waves by one when compared to complexes 2 and 3. Despite
      the decreasing electron density at the terminal or bridging alkenyl bipyridine
      ligand, the anodic redox processes still maintain appreciable ligand character as
      is seen by the shifts of the Ru(CO) and Re(CO)3 stretching frequencies on
      oxidation. Binding of the fac-Re(CO)3X moiety also attenuates the degree of
      ground-state delocalization in the mixed-valent states. 

PMID- 25760817
TI  - Diaphragmatic eventration in children: laparoscopy versus thoracoscopic
      plication.
AB  - AIM: To determine the best way to perform diaphragmatic plication for
      diaphragmatic eventration (DE) using minimally invasive surgery. MATERIALS AND
      METHODS: We conducted a retrospective review of pediatric cases of DE treated
      between 2007 and 2012. Thoracoscopic plication (TP) is performed using single
      lung ventilation with three 5-mm ports; laparoscopic plication (LP) is performed
      using three or four 5-mm ports. The choice of technique was determined
      preferentially by the treating surgeon. RESULTS: There were 20 subjects (13
      treated by LP and 7 treated by TP). Etiology of DE was phrenic nerve injury (LP,
      n=11; TP, n=1) and muscular deficiency (LP, n=2; TP, n=6). Mean age (LP, 18
      months; TP, 25 months) and weight (LP, 8.0 kg; TP, 9.7 kg) at surgery were not
      significantly different. Mean operating time was 155.6 minutes in LP and 167.0
      minutes in TP (P=not significant). Mean intraoperative end-tidal CO2 was 41.9 mm
      Hg (range, 35-52 mm Hg) in LP and 36.9 mm Hg (range, 33-41 mm Hg) in TP (P=.01).
      Mean duration of postoperative ventilation was 1.2 days in LP and 1.3 days in TP
      (P=not significant). Mean time taken to recommence feeding postoperatively was
      1.6 days in both groups (P=not significant). Complications were one conversion to
      thoracotomy in TP, 1 case of atelectasis in each group (P=not significant), and 6
      cases of recurrence in LP versus none in TP (P=.04). CONCLUSIONS: Both TP and LP
      are beneficial for treating small children with DE. However, there is a higher
      incidence of recurrence after LP, and the role of TP in cardiac patients
      requiring subsequent surgery is debatable.

PMID- 25760818
TI  - Comparison of three different methods for effective introduction of platelet-rich
      plasma on PLGA woven mesh.
AB  - For successful tissue regeneration, effective cell delivery to defect site is
      very important. Various types of polymer biomaterials have been developed and
      applied for effective cell delivery. PLGA (poly lactic-co-glycolic acid), a
      synthetic polymer, is a commercially available and FDA approved material.
      Platelet-rich plasma (PRP) is an autologous growth factor cocktail containing
      various growth factors including PDGF, TGFbeta-1 and BMPs, and has shown positive
      effects on cell behaviors. We hypothesized that PRP pretreatment on PLGA mesh
      using different methods would cause different patterns of platelet adhesion and
      stages which would modulate cell adhesion and proliferation on the PLGA mesh. In
      this study, we pretreated PRP on PLGA using three different methods including
      simple dripping (SD), dynamic oscillation (DO) and centrifugation (CE), then
      observed the amount of adhered platelets and their activation stage distribution.
      The highest amount of platelets was observed on CE mesh and calcium treated CE
      mesh. Moreover, calcium addition after PRP coating triggered dramatic activation
      of platelets which showed large and flat morphologies of platelets with rich
      fibrin networks. Human chondrocytes (hCs) and human bone marrow stromal cells
      (hBMSCs) were next cultured on PRP-pretreated PLGA meshes using different
      preparation methods. CE mesh showed a significant increase in the initial cell
      adhesion of hCs and proliferation of hBMSCs compared with SD and DO meshes. The
      results demonstrated that the centrifugation method can be considered as a
      promising coating method to introduce PRP on PLGA polymeric material which could
      improve cell-material interaction using a simple method. 

PMID- 25760819
TI  - Enoyl-coenzyme A hydratase short chain 1 silencing attenuates the proliferation
      of hepatocellular carcinoma by inhibiting epidermal growth factor signaling in
      vitro and in vivo.
AB  - Enoyl-coenzyme A hydratase short chain 1 (ECHS1) regulates fatty acid metabolism
      and is an essential factor in tumor development. The present study aimed to
      investigate the molecular mechanisms of ECHS1 in hepatocellular carcinogenesis by
      studying proliferation and survival in ECHS1 knocked-down hepatocellular
      carcinoma (HCC) cell lines, HepG2 and HuH7. The effect of ECHS1 on tumor
      development was investigated by tumor transplantation in nude mice, and the
      signaling pathways involved in the ECHS1-mediated regulation of HCC cell
      proliferation were identified by western blot analysis. The silencing of ECHS1
      suppressed HCC cell proliferation in vitro and suppressed the growth of
      transplanted tumors in vivo. In addition, the phosphorylation of EGFR and its
      downstream effectors ERK1/2 and AKT was downregulated in ECHS1 knocked-down cells
      and tumor tissues. Furthermore, knockdown of ECHS1 in HCC suppressed cyclin D3
      and cyclin dependent kinase 6 expression, whilst enhancing p16 and p21
      expression. Therefore, ECHS1 may also be involved in cell cycle progression in
      HCC cells. These results suggested that ECHS1 may promote cell proliferation in
      HCC in an EGFR-dependent manner.

PMID- 25760824
TI  - The portrayal of albinism in pop culture: a 360 degrees  change from previous
      ideology.

PMID- 25760821
TI  - Rejuvenating the senescent heart.
AB  - PURPOSE OF REVIEW: The purpose of this review is to provide an update on the
      cardiac stem cell field with an emphasis on aging and to suggest some relevant
      strategies directed toward rejuvenation of the senescent heart. RECENT FINDINGS:
      Stem cells were long considered as a fountain of youth and were assumed to be
      equipped against any form of aging effect. However, it is now clear that stem
      cells suffer the consequences of aging as well. With the discovery that cardiac
      stem cells reside in the heart comes the question whether these cells are also
      impaired upon aging. As cardiac stem cell properties are also altered with age,
      autologous stem cell-based therapy to treat heart failure will benefit from new
      improved strategies. SUMMARY: With the goal to improve stem cell properties that
      are impaired upon aging, some strategies are highlighted. Genetic modification of
      adult human cardiac progenitor cells prior to autologous stem cell-based therapy,
      delivery of the next generation of stem cells such as CardioChimeras and
      CardioClusters, and improvement of the myocardial environment with rejuvenating
      factors constitute some of the possibilities and are discussed in more detail in
      this review.

PMID- 25760825
TI  - Jonathan Hutchinson: the greatest syphilographer of all time.

PMID- 25760826
TI  - The evolution of dermatology grand rounds: from Alibert to Osler.

PMID- 25760827
TI  - To tell the truth.

PMID- 25760828
TI  - Lichen planus.

PMID- 25760830
TI  - Stereoselective assembly of amino acid-based metal-biomolecule nanofibers.
AB  - A series of amino acid-based metal-biomolecule nanofibers are fabricated through
      a coordination-directed assembly process. The chirality and carbon chain length
      of the amino acids exert a pronounced influence on the assembly process. This
      study may be extended to design diverse kinds of 1-D metal-biomolecule frameworks
      (MBioFs). 

PMID- 25760829
TI  - Strong nonadditivity as a key structure-activity relationship feature:
      distinguishing structural changes from assay artifacts.
AB  - Nonadditivity in protein-ligand affinity data represents highly instructive
      structure-activity relationship (SAR) features that indicate structural changes
      and have the potential to guide rational drug design. At the same time,
      nonadditivity is a challenge for both basic SAR analysis as well as many ligand
      based data analysis techniques such as Free-Wilson Analysis and Matched Molecular
      Pair analysis, since linear substituent contribution models inherently assume
      additivity and thus do not work in such cases. While structural causes for
      nonadditivity have been analyzed anecdotally, no systematic approaches to
      interpret and use nonadditivity prospectively have been developed yet. In this
      contribution, we lay the statistical framework for systematic analysis of
      nonadditivity in a SAR series. First, we develop a general metric to quantify
      nonadditivity. Then, we demonstrate the non-negligible impact of experimental
      uncertainty that creates apparent nonadditivity, and we introduce techniques to
      handle experimental uncertainty. Finally, we analyze public SAR data sets for
      strong nonadditivity and use recourse to the original publications and available
      X-ray structures to find structural explanations for the nonadditivity observed.
      We find that all cases of strong nonadditivity (DeltaDeltapKi and DeltaDeltapIC50
      > 2.0 log units) with sufficient structural information to generate reasonable
      hypothesis involve changes in binding mode. With the appropriate statistical
      basis, nonadditivity analysis offers a variety of new attempts for various areas
      in computer-aided drug design, including the validation of scoring functions and
      free energy perturbation approaches, binding pocket classification, and novel
      features in SAR analysis tools. 

PMID- 25760832
TI  - [Clinical analysis of 101 cases of neonatal intestinal perforation].
AB  - OBJECTIVE: To analyze the clinical characteristics of neonatal intestinal
      perforation and to provide a theoretical basis for improving the prognosis of
      this disease. METHODS: The clinical data of 101 patients with neonatal intestinal
      perforation who were hospitalized in the Neonatal Intensive Care Unit between
      January 2000 and June 2014 were retrospectively reviewed. RESULTS: The main
      causes of neonatal intestinal perforation were neonatal necrotizing enterocolitis
      (NEC, 41 cases, 40.6%), idiopathic intestinal perforation (17 cases, 16.8%), and
      congenital megacolon (10 cases, 9.9%). The average birth weight and average
      gestational age of the idiopathic intestinal perforation group were significantly
      higher than those of the NEC group (P<0.05). The main pathogen of the NEC group
      was enterococci, which accounted for 57% (13/23), while in the idiopathic
      intestinal perforation group Gram-negative bacteria became the major pathogen;
      the distribution of pathogens were significantly different between the two groups
      (P<0.05). Multiple logistic regression analysis found that acidosis, multi-site
      intestinal perforation, and prolonged perforation-operation interval were
      independent risk factors for death due to neonatal intestinal perforation.
      CONCLUSIONS: Multiple causes contribute to neonatal intestinal perforation, and
      NEC is the major one. Neonatal intestinal perforation caused by NEC has different
      pathogens compared with idiopathic intestinal perforation, and the two diseases
      may be mutually independent. Early diagnosis and timely operation is the main
      measure to rescue the lives of patients with neonatal intestinal perforation.

PMID- 25760831
TI  - High-mobility group nucleosome-binding domain 2 protein inhibits the invasion of
      Klebsiella pneumoniae into mouse lungs in vivo.
AB  - Since bacterial invasion into host cells is a critical step in the infection
      process and the predominance of multiple-antibiotic-resistant Klebsiella (K.)
      pneumoniae strains, using molecular agents to interfere with K. pneumoniae
      invasion is an attractive approach for the prevention of infection and suppress
      the immune inflammatory response. In previous studies by our group, high-mobility
      group nucleosome-binding domain 2 (HMGN2) protein was shown to exhibit anti
      bacterial activity in vitro. The objective of the present study was to
      investigate the effects of HMGN2 protein on the invasion of K. pneumoniae 03183
      in vivo. The results showed that pre-treatment with 128 ug/ml HMGN2 significantly
      reduced K. pneumoniae 03183 invasion into mouse lungs and increased the mRNA
      expression of CXCL1 and LCN2 within 2 h. Immunohistochemical staining showed that
      F-actin expression was significantly decreased, and fluorescence microscopy and
      western blot analysis further demonstrated that HMGN2 significantly blocked K.
      pneumoniae 03183-induced actin polymerization. These changes implied that HMGN2
      may provide protection against K. pneumoniae 03183 infection in vivo.

PMID- 25760833
TI  - [Changes of plasma cardiotrophin-1 levels in neonates with myocardial ischemic
      injury].
AB  - OBJECTIVE: To study the changes and significance of plasma cardiotrophin-1 (CT-1)
      in neonates with hypoxic-ischemic encephalopathy (HIE) complicated by myocardial
      ischemic injury. METHODS: Forty-five neonates with HIE (15 mild cases, 24
      moderate cases and 6 severe cases) were enrolled and divided into two subgroups
      based on the presence of myocardial injury (n=19) and not (n=26). Twenty healthy
      neonates were used as the control group. Plasma CT-1 levels were measured using
      double-antibody sandwich enzyme immunoassay method. Serum creatinine kinase MB
      (CK-MB) and cardiac troponin I (CTnI ) levels were also measured. RESULTS: Plasma
      CT-1 levels in the mild HIE (169+/-20 pg/mL) and moderate/severe HIE subgroups
      (287+/-44 pg/mL) were significantly higher than those in the control group (30+/
      8 pg/mL), and plasma CT-1 levels were associated with the severity of HIE
      (P<0.01). Plasma CT-1 levels were positively correlated with serum CK-MB and CTnI
      levels in neonates with HIE in the acute phase (r=0.565 and 0.621 respectively;
      P<0.01). Plasma CT-1 levels in neonates with myocardial injury were significantly
      higher than those without myocardial injury (249 +/-35 pg/mL vs 177+/-26 pg/mL;
      P<0.01). Plasma CT-1 levels were significantly reduced in neonates with
      myocardial injury in the convalescent phase (157+/-19 pg/mL) compared with those
      in the acute phase (249+/-35 pg/mL; P<0.01). CONCLUSIONS: Detection of plasma CT
      1 levels may be useful in the diagnosis of myocardial ischemic injury and the
      severity evaluation of HIE.

PMID- 25760834
TI  - [Long-term clinical efficacy of mild hypothermia therapy in neonates with hypoxic
      ischemic encephalopathy: a Meta analysis].
AB  - OBJECTIVE: To systematically evaluate the long-term clinical efficacy and safety
      of mild hypothermia therapy in neonates with hypoxic-ischemic encephalopathy
      (HIE). METHODS: All randomized controlled trials (RCTs) of mild hypothermia
      therapy for neonatal HIE from inception to March 2014 were retrieved from
      databases including Cochrane Library, PubMed, Embase, CBMdisc, and Wanfang Data.
      Meta analysis was performed using RevMan 5.1 Software. RESULTS: Eight RCTs met
      the search criteria. The results of Meta analysis showed that, compared with the
      control group, systemic hypothermia significantly reduced the mortality rate and
      the incidence of growth delay (RR=0.73, 95% CI: 0.61-0.89; RR=0.70, 95%CI: 0.54
      0.93); selective head or systemic hypothermia therapy significantly reduced the
      incidence of cerebral palsy (RR=0.65, 95%CI: 0.46-0.94; RR=0.67, 95%CI: 0.52
      0.86) up to 12-24 months of age. One study reported that hypothermia reduced the
      mortality rate and the rate of a composite end point of death or severe
      disability compared with the control group at 6 to 7 years of age. The incidence
      of adverse events including sinus bradyarrhythmia, thrombocytopenia and
      hypoglycemia was significantly higher in the hypothermia group than in the
      control group, whereas the incidence of cardiac arrhythmia, hypotension,
      thrombosis or bleeding, hypokalemia, sepsis, and liver dysfunction showed no
      significant differences between the two groups. CONCLUSIONS: Mild hypothermia
      therapy demonstrates a significant efficacy in children with HIE up to 12-24
      months of age, but there is still a need for further research on childhood
      outcomes after mild hypothermia for neonatal HIE. This therapy has few adverse
      effects and a high clinical tolerability.

PMID- 25760835
TI  - [What is the optimal oxygen saturation for extremely premature infants? A Meta
      analysis].
AB  - OBJECTIVE: To explore an optimal oxygen saturation for extremely preterm infants
      based on a systemic review of the published studies. METHODS: A Meta analysis of
      the published studies by the NeOProM Group which compared the outcomes of
      extremely preterm infants (gestational age <28 weeks) maintained in either a low
      (85%-89%) or high (91%-95%) oxygen saturation (SpO2) by using the STATA 12.0. The
      outcomes measured included the mortality and the incidences of retinopathy of
      prematurity (ROP), necrotizing enterocolitis of newborn (NEC), broncho-pulmonary
      dysplasia (BPD), intraventricular hemorrhage (IVH) and patent ductus arteriosus
      (PDA). RESULTS: Three studies were included, in which 2 460 infants were assigned
      into the low SpO2 group and 2 459 infants in the high SpO2 group. The Meta
      analysis demonstrated that the risk of mortality before discharge or at the age
      of 18 months increased in the low SpO2 group compared with the high SpO2 group
      (RR: 1.19; 95%CI: 1.05-1.35); the risk of ROP decreased in the low SpO2 group
      (RR: 0.73; 95%CI: 0.53-1.00); the risk of NEC increased in the low SpO2 group
      (RR: 1.26; 95%CI: 1.06-1.49). There was no significance in the incidences of BPD,
      IVH and PDA between the two groups. CONCLUSIONS: Maintaining SpO2 at 85%-89% may
      decrease the incidence of ROP, but increase the mortality rate and the incidence
      of NEC in extremely premature infants.

PMID- 25760836
TI  - [Utility of fractional exhaled nitric oxide in children with asthma].
AB  - OBJECTIVE: To study the utility of fractional exhaled nitric oxide (FeNO) in
      young children at different stages of asthma. METHODS: Fifty-eight children with
      newly diagnosed asthma (aged 1-3 years) at the acute exacerbation stage between
      April and June, 2014 were recruited. After 3 months' treatment, the children
      switched into the chronic persistent stage (n=34) or remission stage (n=24).
      Thirty aged-matched healthy children served as controls. FeNO levels and lung
      function were measured for all subjects. The best cut-off value of FeNO for the
      diagnosis of asthma was evaluated by receiver operating characteristic (ROC)
      curve. RESULTS: The FeNO levels in children with asthma at various stages were
      higher than controls (P<0.05). The FeNO levels in the acute exacerbation stage
      were highest, followed by the chronic persistent stage (P<0.05). FeNO level was
      correlated to the stages of asthma (r=-0.382, P<0.001). The cut-off value of FeNO
      for the diagnosis of asthma was 22.75 ppb by ROC curve, with the sensitivity of
      0.933 and the specificity of 0.388. CONCLUSIONS: The children with asthma at
      different stages have different FeNO levels. Measurement of FeNO is useful in the
      diagnosis of asthma in young children.

PMID- 25760837
TI  - [The comparison of clinical features in children with different control levels of
      asthma].
AB  - OBJECTIVE: To compare the clinical features in children with different control
      levels of asthma and to explore the factors influencing asthma control. METHODS:
      A cross-sectional study was performed on 115 children diagnosed with asthma
      between October 2013 and February 2014. All the patients were classified into two
      groups: fully controlled group (n=65) and non-fully controlled group (n=55),
      according to the Children Bronchial Asthma Prevention and Treatment Guideline
      (2008 version) and the asthma control test results. The differences of clinical
      features between the two groups were compared. The quality of life was evaluated
      by an asthma-related quality of life questionnaire. The main factors influencing
      asthma control were analyzed by the logistic regression method. RESULTS: There
      were significant differences in the frequencies of respiratory tract infection
      and acute asthma attacks within the 3 months, and unplanned hospital visits due
      to acute asthma attacks between the fully controlled and non-fully controlled
      groups (P<0.05). The scores of asthma-related quality of life in the fully
      controlled group were significantly lower than in the non-fully controlled group
      in children under 7 years old. In contrast, the scores of asthma-related quality
      of life in the fully controlled group were significantly higher than in the non
      fully controlled group in children at the age of 7-16 years (P<0.05). The
      logistic regression analysis showed that the patients without experiencing
      regular hospital visits (OR=7.715) and with allergic rhinitis (OR=5.531) had
      increased risks for poor asthma control and that the patients with other allergic
      diseases (eg. eczema, food allergy) had decreased risks for poor asthma control
      (OR=0.299). CONCLUSIONS: The appearance of some clinical features suggests that
      the asthmatic children may be in the status of poor asthma control and need an
      active intervention. A poor asthma control status can result in a decreased
      quality of life. To improve the asthma control level, the incidence of allergic
      rhinitis should be reduced and a regular hospital visit should be performed in
      the children.

PMID- 25760838
TI  - [Association between CHI3L1 SNPs and susceptibility to childhood asthma].
AB  - OBJECTIVE: To investigate the association between CHI3L1 single nucleotide
      polymorphisms (SNPs) and the susceptibility to childhood asthma. METHODS: A total
      of 316 children diagnosed with asthma between January 2011 and October 2013 and
      297 healthy children were selected as asthma group and control group
      respectively. Peripheral blood samples were collected from all subjects.
      Chemiluminescence and flow cytometry were applied to measure total IgE level and
      the percentage of eosinophils. ELISA was used to measure YKL-40 level. Genomic
      DNA was extracted from peripheral blood hemocytes, and the genotype and allele
      frequencies at CHI3L1 SNPs rs4950928, rs10399805, and rs883125 were determined by
      MALDI-TOP mass spectrometry. RESULTS: The total IgE and YKL-40 levels were
      significantly higher in the asthma group than in the control group (P<0.05),
      while the percentage of eosinophils showed no significant difference between the
      two groups (P>0.05). The frequency of GG genotype at rs883125 in the asthma group
      was significantly higher than that in the control group (P<0.05). For rs4950928,
      the asthma group had a significantly lower frequency of CC genotype (P<0.05) but
      a significantly higher frequency of CG genotype (P<0.05) compared with the
      control group. In the asthma group, the patients with GG and CG genotypes at
      rs4950928 had significantly increased total IgE and YKL-40 levels compared with
      those with CC genotype at this locus (P<0.05). CONCLUSIONS: YKL-40 is a potential
      molecular biomarker for the primary diagnosis of childhood asthma. CHI3L1 SNPs
      rs4950928 and rs883125 may be associated with childhood asthma. G allele at
      rs4950928 may increase the risk of childhood asthma.

PMID- 25760839
TI  - [Epidemiological survey of asthma among children aged 0-14 years in 2010 in urban
      Zhongshan, China].
AB  - OBJECTIVE: To investigate the prevalence, current treatment, and clinical
      characteristics of asthma, as well as the risk factors for this disease, among
      children aged 0-14 years in 2010 in urban Zhongshan, China. METHODS: A total of
      10 336 children aged 0-14 years were selected from urban Zhongshan by cluster
      random sampling. The Third National Childhood Asthma Epidemiological
      Questionnaire 2010 was used to analyze the prevalence, current treatment, and
      clinical characteristics of childhood asthma, as well as the risk factors for
      this disease. RESULTS: Asthma was diagnosed in 179 cases (1.73%). The prevalence
      of asthma in male children was significantly higher than that in female children
      (2.25% vs 1.16%; P<0.01). Of the 179 patients, severe attacks were common in 104
      cases (58.1%), 110 cases (61.5%) had slow onset, 102 cases (57.0%) had gradually
      relieved conditions, 61 cases (34.1%) suffered from asthma during seasonal
      transition, and 150 cases (83.8%) developed asthma due to respiratory tract
      infection. Among all asthmatic children, 71.5% had been treated with inhaled
      corticosteroids, and 71.5% had been treated with bronchodilator. The multivariate
      logistic regression analysis showed that a history of penicillin allergy, a
      family history of allergy, food allergy, eczema, allergic rhinitis, cesarean
      delivery, family mould, and perinatal passive smoking were independent risk
      factors for childhood asthma. CONCLUSIONS: The prevalence of childhood asthma in
      urban Zhongshan is on a high level, and is associated with gender. The treatment
      of asthma has been standardized, but still needs further improvement. The onset
      of asthma attack is influenced by various factors.

PMID- 25760840
TI  - [Roles of CXCR3 on lymphocytes and IP-10 of peripheral blood in infants with
      bronchiolitis].
AB  - OBJECTIVE: To study the roles of chemokine receptor 3 (CXCR3) on lymphocytes and
      interferon-gamma-inducible protein-10 (IP-10) of peripheral blood in childhood
      bronchiolitis. METHODS: Fifty-five children with bronchiolitis were classified
      into Group I (with allergic factors) and Group II (without allergic factors).
      Twenty-eight children with noninfectious diseases were enrolled randomly as the
      control group. The expression of CXCR3 (CD183 as its molecular marker) on
      lymphocytes of peripheral blood was detected by flow cytometry. Serum IP-10 level
      was measured using ELISA. RESULTS: The expression of CD183(+) cells on CD4(+) and
      CD8(+) lymphocytes in peripheral blood in children with bronchiolitis from both
      Group I and Group II was significantly higher than that in the control group
      (P<0.05), and Group I had higher expression of CD183(+) cells on CD4(+) and
      CD8(+) lymphocytes than Group II (P<0.05).Serum IP-10 levels in Group I and Group
      II were significantly higher than those in the control group (P<0.05). However,
      there was no significant difference in serum IP-10 levels between Group I and
      Group II. CONCLUSIONS: CXCR3 and IP-10 are involved in the pathogenesis of
      bronchiolitis, and CXCR3 is associated with allergic factors.

PMID- 25760841
TI  - [Expression of CysLTR-1 and CysLTR-2 in adenoid tissues from children with
      adenoid hypertrophy].
AB  - OBJECTIVE: To examine the expression of cysteinyl leukotriene receptor-1 (CysLTR
      1) and cysteinyl leukotriene receptor-2 (CysLTR-2) in the adenoid tissues from
      children with adenoid hypertrophy (AH) and to explore the role of leukotrienes in
      the pathogenesis of AH. METHODS: Sixty children with AH who were treated by
      adenoidectomy and/or tonsillectomy were classified into two groups: simple AH and
      AH plus allergic rhinitis (n=30 each). Twenty children who underwent
      tonsillectomy due to recurrent purulent tonsillitis were selected as the control
      group. The expression of CysLTR-1 and CysLTR-2 in the excised tonsil and/or
      adenoid tissues was determined by immunofluorescence histochemical labeling and
      integrated optical density measurement. RESULTS: The expression of CysLTR-1 and
      CysLTR-2 in the adenoid and tonsil tissues increased significantly in both the
      simple AH group and AH plus allergic rhinitis group compared with the control
      group (P<0.01). The expression of CysLTR-1 and CysLTR-2 in the AH plus allergic
      rhinitis group increased more significantly compared with the simple AH group
      (P<0.01). CONCLUSIONS: CysLTR-1 and CysLTR-2 are highly expressed in the adenoid
      tissues from children with AH, suggesting that leukotrienes are involved in the
      pathogenesis of AH.

PMID- 25760842
TI  - [Association of CCR2 gene rs1799864 polymorphism with hemophagocytic
      lymphohistiocytosis in children].
AB  - OBJECTIVE: To investigate the association between rs1799864 single nucleotide
      polymorphism (SNP) of the C-C chemokine receptor 2 (CCR2) gene and susceptibility
      of hemophagocytic lymphohistiocytosis (HLH) in children. METHODS: The clinical
      and laboratory data of 86 children diagnosed with HLH between January 2007 and
      December 2013 were retrospectively reviewed. The CCR2 gene rs1799864 was
      genotyped by SNaPshot technique in 86 HLH children and 128 healthy controls. The
      genotypic and allelic frequencies in the two groups were comparatively analyzed.
      RESULTS: No significant difference either in genotypic or allelic frequencies of
      rs1799864 polymorphism of the CCR2 gene was observed between HLH patients and
      controls (P>0.05), but there were significant differences in the age of onset and
      the periods of temperature and platelet returning to normal after treatment
      (P<0.05). CONCLUSIONS: There is no association between CCR2 gene rs1799864
      polymorphism and the risk for HLH in children. However, the genotypic differences
      of this polymorphism might be associated with clinical characteristics and
      prognosis of HLH.

PMID- 25760843
TI  - [Prognostic impact of loss of sex chromosomes in children with acute myeloid
      leukemia subtype M2].
AB  - OBJECTIVE: To study the relationship between loss of sex chromosomes and
      prognosis in children with acute myeloid leukemia (AML) M2 subtype. METHODS:
      According to cytogenetic characteristics, 106 children with AML were divided into
      three groups: patients with normal karyotype (Group A, n=26), patients with
      abnormal karyotype who had no loss of sex chromosomes (Group B, n=52), and
      patients with abnormal karyotype who had loss of sex chromosomes (Group C, n=28).
      Prognosis was compared between the three groups. RESULTS: The 5-year event-free
      survival (EFS) rates of Groups A, B, and C were (38.9+/-11.2)%, (59.3+/-7.3)%,
      and (66.5+/-10.5)%, respectively; the EFS of Group C was significantly higher
      than that of Group A (P=0.035). The 5-year overall survival (OS) rates of Groups
      A, B, and C were (54.3+/-13.5)%, (68.1+/-7.7)%, and (77.9+/-9.8)%, respectively
      (P>0.05). The 5-year EFS of 58 patients with t(8;21) was (63.3+/-7.3)%,
      significantly higher than that of patients with normal karyotype (P=0.015). All
      the 28 cases in Group C had t(8;21), and their 5-year EFS was not significantly
      different from that of patients with t(8;21) in Group B (P>0.05). CONCLUSIONS:
      Loss of sex chromosomes is a favorable karyotype in children with AML M2 subtype
      and the patients in this group mostly have t(8;21). Why loss of sex chromosomes
      indicates a favorable prognosis is probably because it is accompanied by t(8;21)
      in the patients.

PMID- 25760844
TI  - [A Chinese boy with methylmalonic aciduria cblB type and a novel mutation in the
      MMAB gene].
AB  - cblB defect is a rare type of methylmalonic aciduria. In this study, a Chinese
      boy was diagnosed with methylmalonic aciduria cblB type and a novel mutation in
      the MMAB gene. The clinical presentations, blood acylcarnitines profiles, urine
      organic acids and genetic features of the patient were reported. The boy
      presented with fever, feeding difficulty and lethargy at the age of 2 months.
      Seven days later, he had coma, cold limb, thrombocytopenia, metabolic acidosis
      and liver damage. His blood propionylcarnitine and urinary methylmalonic acid
      levels increased significantly, but the plasma total homocysteine level was in
      the normal range, which supported the diagnosis of isolated methylmalonic
      aciduria. Gene analysis was performed by direct sequencing. No mutation in the
      MUT gene was found. However, a reported mutation c.577G>A (p.E193K) and a novel
      mutation c.562G>A (p.V188M) in the MMAB gene were identified, which confirmed the
      diagnosis of methylmalonic aciduria cblB type. Progressive clinical and
      biochemical improvement has been observed after hydroxylcobalamin injection,
      protein-restricted diet with the supplements of special formula and L-carnitine.
      He is currently 3 years and 11 months old and has a normal development condition.
      The phenotypes of the patients with cblB defect are nonspecific. Metabolic
      analysis and MMAB gene analysis are keys for the diagnosis of the disorder. 

PMID- 25760845
TI  - [Changing trends and clinical characteristics of febrile seizures in children].
AB  - OBJECTIVE: To investigate the clinical characteristics and changing trends of
      febrile seizures (FS) in children. METHODS: The clinical data of 1 922 children
      with FS admitted from 2004 to 2013 were analyzed retrospectively. The clinical
      characteristics and changing trends of FS in the two five-year periods were
      analyzed. RESULTS: In 1 922 children with FS, the male/female ratio was 2.27:1.
      The mean age at onset was 3.0+/-1.8 years, while the peak age at onset was 1-3
      years. There were 1 556 children (80.96%) with simple FS and 366 (19.04%) with
      complex FS. The number of children with FS in the second five-year period (1 202
      cases) increased by 66.9% compared with that in the first five-year period (720
      cases). The proportion of children with complex FS was significantly higher in
      the second five-year period than in the first five-year period (21.13% vs 15.56%;
      P<0.05). In children with simple FS, there were no significant differences in the
      age and body temperature at onset, convulsion duration, and the incidence of
      complications between the two five-year periods (P>0.05). However, children with
      complex FS had a significantly lower age at onset, a significantly lower body
      temperature at onset, a significantly longer convulsion duration, and a
      significantly higher incidence of complications including myocardial injury and
      hyponatremia in the second five-year period than in the first five-year period
      (P<0.05). CONCLUSIONS: In the last decade, the number of children with FS and
      incidence of complex FS increased, and the outcome became worse according to
      clinical characteristics, suggesting that more attention should be paid to timely
      diagnosis and treatment of complex FS.

PMID- 25760846
TI  - [Diagnostic value of the propranolol-exercise provocative test for growth hormone
      deficiency in children].
AB  - OBJECTIVE: To assess the diagnostic value of the propranolol-exercise provocative
      test for growth hormone deficiency (GHD) in children. METHODS: This study
      included 120 children who received both the insulin provocative test and the
      propranolol-exercise provocative test due to short stature between January 2009
      and March 2013. Growth hormone (GH) levels in venous blood were measured before
      and after the provocative test. Peak GH <10 ng/mL was defined as negative
      stimulation, while peak GH >=10 ng/mL was defined as positive stimulation. The
      children whose peak GH levels were <10 ng/ mL after both tests were diagnosed
      with GHD. RESULTS: Twenty-nine (24.2%) of the 120 children with short stature
      were diagnosed with GHD. The positive rate in the insulin provocative test was
      48.3%, versus 65.8% in the propranolol-exercise provocative test. The overall
      coincidence rate and positive coincidence rate of the two tests were 62.5% and
      79.3%, respectively. The peak GH after the propranolol-exercise provocative test
      was significantly higher than that after the insulin provocative test (P<0.01).
      Peak GH occurred mostly at 30-60 minutes after the insulin provocative test,
      while that occurred mostly at 120 minutes after the propranolol-exercise
      provocative test. No adverse effects were observed in the propranolol-exercise
      provocative test. CONCLUSIONS: Coincidence rates in stimulating the secretion of
      GH are high between the propranolol-exercise provocative test and the insulin
      provocative test. Compared with the insulin provocative test, the propranolol
      exercise provocative test is more likely to stimulate the secretion of GH. GHD
      can be clinically diagnosed by the insulin provocative test combined with the
      propranolol-exercise provocative test.

PMID- 25760847
TI  - [Effect of NF-kappaB on proliferation of rat pulmonary artery smooth muscle cells
      inhibited by simvastatin].
AB  - OBJECTIVE: To explore the effects of NF-kappaB on proliferation of rat pulmonary
      artery smooth muscle cells (PASMC) inhibited by simvastatin. METHODS: PASMC
      isolated from rats and cultured in vitro were randomly divided into four groups
      (n=6 each): control, platelet-derived growth factor (PDGF) treatment,
      PDGF+simvastatin treatment, and PDGF+simvastatin+parthenolide (NF-kappaB
      inhibitor) treatment. MTT colorimetric assay and flow cytometry were performed to
      detect cell proliferation and cell cycle distribution. Immunohistochemistry was
      performed to detect the expression of NF-kappaB protein. Real-Time PCR was
      performed to detect NF-kappaB mRNA expression. RESULTS: Compared with the control
      group, MTT values of PASMC at all time points, cell proportion at the S phase and
      G2+M phase, NF-kappaB protein and mRNA expression increased significantly in the
      PDGF group (P<0.05). With the intervention of simvastatin, the levels of above
      indexes decreased compared with the PDGF group (P<0.05). With the intervention of
      simvastatin and parthenolide, the levels of above indexes decreased more
      obviously, but were not significantly different from those in the simvastatin
      intervention group. CONCLUSIONS: Simvastatin can inhibit proliferation of PASMC
      and cell cycle process. NF-kappaB may play an important role in the inhibitory
      effect of simvastatin on the proliferation of PASMC.

PMID- 25760848
TI  - [Effects of different doses of 1,25-(OH)2D3 on expression of HMGB1 and IL-17 in
      the lungs of asthmatic mice].
AB  - OBJECTIVE: To study the effects of 1,25-(OH)(2)D(3) on airway remodeling and
      expression of high mobility group box 1 (HMGB1) and IL-17 in asthmatic mice.
      METHODS: Fifty female mice were randomly divided into 5 groups: control, asthma,
      low-dose, middle-dose, and high-dose intervention groups (n=10 each). Asthma was
      induced by intraperitoneal injections of ovalbumin (OVA) and aerosol inhalation
      of OVA solution. The low-dose, middle-dose, and high-dose intervention groups
      were administered with 1,25-(OH)(2)D(3) solution at the dosage of 1, 4 and 10
      MUg/kg respectively by intraperitoneal injections before asthma challenge. The
      airway structural changes were assessed by hematoxylin and eosin staining. mRNA
      expression levels of HMGB1 and IL-17 in the lung tissues were evaluated by RT
      PCR. The protein levels of HMGB1 and IL-17 in the lung tissues were observed by
      immunohistochemistry. RESULTS: The airway wall thickness, protein and mRNA
      expression levels of HMGB1 and IL-17 were higher in the untreated asthma group
      than in the control group (P<0.05). The airway wall thickness, protein and mRNA
      expression levels of HMGB1 and IL-17 were lower in the middle-dose and low-dose
      intervention groups than in the untreated asthma group, and the middle-dose
      intervention group demonstrated lower airway wall thickness, protein and mRNA
      expression levels of HMGB1 and IL-17 than in the low-dose intervention group
      (P<0.05). However, the airway wall thickness, protein and mRNA expression levels
      of HMGB1 and IL-17 in the high-dose intervention group were higher than in the
      untreated asthma group (P<0.05). CONCLUSIONS: HMGB1 and IL-17 may be involved in
      the airway remodeling process in asthmatic mice. A moderate amount of HMGB1 and
      IL-17 may be involved in the airway remodeling process in asthmatic mice. A
      moderate amount of 1,25-(OH)(2)D(3) can improve the airway remodeling, but a
      higher dose of 1,25-(OH)(2)D(3) may affect adversely the airway remodeling
      process.

PMID- 25760849
TI  - [Clinical analysis of 94 cases of infantile ulcerated hemangioma].

PMID- 25760850
TI  - [Calcifying aponeurotic fibroma of the right shoulder in an infant].

PMID- 25760851
TI  - [Roles of microRNAs in epilepsy].
AB  - MicroRNAs (miRNAs) are short, noncoding RNAs that function as posttranscriptional
      regulators of gene expression by controlling the translation of messenger RNAs.
      Epilepsy is a chronic and debilitating brain disorder and occurs frequently in
      childhood. The brain expresses several unique miRNAs which are associated with
      epileptogenesis. As a new layer of gene expression in the pathogenesis of
      epilepsy, miRNAs have shed a new light on the potential to transform an
      understanding of the underlying mechanisms promising novel therapeutic targets
      and effective antiepileptogenic medications. This article reviews the roles and
      mechanisms of miRNAs in the pathogenesis of seizure-damage and pathophysiology of
      epileptogenesis. 

PMID- 25760852
TI  - Probing the reactivity of microhydrated alpha-nucleophile in the anionic gas
      phase S(N)2 reaction.
AB  - To probe the kinetic performance of microsolvated alpha-nucleophile, the G2(+)M
      calculations were carried out for the gas-phase S(N)2 reactions of monohydrated
      and dihydrated alpha-oxy-nucleophiles XO(-)(H2O)(n = 1,2) (X = HO, CH3O, F, Cl,
      Br), and alpha-sulfur-nucleophile, HSS(-)(H2O)(n = 1,2), toward CH3Cl. We
      compared the reactivities of hydrated alpha-nucleophiles to those of hydrated
      normal nucleophiles. Our calculations show that the alpha-effect of monohydrated
      and dihydrated alpha-oxy-nucleophiles will become weaker than those of unhydrated
      ones if we apply a plot of activation barrier as a function of anion basicity.
      Whereas the enhanced reactivity of monohydrated and dihydrated ROO(-) (R = H, Me)
      could be observed if compared them with the specific normal nucleophiles, RO(-)
      (R = H, Me). This phenomena can not be seen in the comparisons of XO(-)(H2O)(n =
      1,2) (X = F, Cl, Br) with ClC2H4O(-)(H2O)(n = 1,2), a normal nucleophile with
      similar gas basicity to XO(-)(H2O)(n = 1,2). These results have been carefully
      analyzed by natural bond orbital theory and activation strain model. Meanwhile,
      the relationships between activation barriers with reaction energies and the
      ionization energies of alpha-nucleophile are also discussed.

PMID- 25760853
TI  - Still Trapped in the U.S. Media's Closet: Representations of Gender-Variant, Pre
      Adolescent Children.
AB  - Many studies have examined representations of gay, lesbian, bisexual, and
      transgender (LGBT) people in the U.S. media. Yet they have centered on portrayals
      of adults or teenagers. This investigation considered a potential LGBT population
      that has been neglected in media research, namely gender-variant, preadolescent
      children. Surveying the U.S. media at large but with an emphasis on television,
      the article reveals that gender-creative youth are nearly invisible. When
      depictions of gender-variant kids do appear, they often focus on either children
      who express extreme gender dysphoria or in some way signify the "tragic queer"
      motif (or both). The implications of these findings are discussed. 

PMID- 25760854
TI  - Behavior and Fate of Halloysite Nanotubes (HNTs) When Incinerating PA6/HNTs
      Nanocomposite.
AB  - Nanoclay-based nanocomposites have been widely studied and produced since the
      late 1990s, and frequently end up in waste disposal plants. This work
      investigates the behavior of PA6/HNTs nanocomposites (nylon-6 incorporating
      halloysite nanotubes) during incineration. Incineration tests were performed at
      lab-scale using a specific tubular furnace modified in order to control the key
      incineration parameters within both the combustion and postcombustion zones. The
      combustion residues and combustion aerosol (particulate matter and gas phase)
      collected downstream of the incinerator furnace were characterized using various
      aerosol analysis techniques. Time tracking of the gas and particle-number
      concentrations revealed two-step char formation during combustion. HNTs
      transformed into other mineral structures which were found in both the aerosol
      and the residues. During combustion of the polymer, it appears that HNTs
      contribute to the formation of a cohesive char layer that protects the residual
      material. 

PMID- 25760855
TI  - A novel human mutation in the SLC9A1 gene results in abolition of Na+/H+
      exchanger activity.
AB  - The SLC9A1 gene, the Na+/H+ exchanger isoform 1 is the principal plasma membrane
      Na+/H+ exchanger of mammalian cells and functions by exchanging one intracellular
      proton for one extracellular sodium. The human protein is 815 amino acids in
      length. Five hundred N-terminal amino acids make up the transport domain of the
      protein and are believed to form 12 transmembrane segments. Recently, a genetic
      mutation of the Na+/H+ exchanger isoform 1, N266H, was discovered in a human
      patient through exome sequencing. We examined the effect of this mutation on
      expression, targeting and activity of the Na+/H+ exchanger. Mutant N266H protein
      was expressed in AP-1 cells, which lack their endogenous Na+/H+ exchanger
      protein. Targeting of the mutant protein to the cell surface was normal and
      expression levels were only slightly reduced relative to the wild type protein.
      However, the N266H mutant protein had no detectable Na+/H+ exchanger activity. A
      histidine residue at this location may disrupt the cation binding site or the
      pore of the Na+/H+ exchanger protein. 

PMID- 25760856
TI  - Variation in responses of fishes across multiple reserves within a network of
      marine protected areas in temperate waters.
AB  - Meta-analyses of field studies have shown that biomass, density, species
      richness, and size of organisms protected by no-take marine reserves generally
      increase over time. The magnitude and timing of changes in these response
      variables, however, vary greatly and depend upon the taxonomic groups protected,
      size and type of reserve, oceanographic regime, and time since the reserve was
      implemented. We conducted collaborative, fishery-independent surveys of fishes
      for seven years in and near newly created marine protected areas (MPAs) in
      central California, USA. Results showed that initially most MPAs contained more
      and larger fishes than associated reference sites, likely due to differences in
      habitat quality. The differences between MPAs and reference sites did not greatly
      change over the seven years of our study, indicating that reserve benefits will
      be slow to accumulate in California's temperate eastern boundary current. Fishes
      in an older reserve that has been closed to fishing since 1973, however, were
      significantly more abundant and larger than those in associated reference sites.
      This indicates that reserve benefits are likely to accrue in the California
      Current ecosystem, but that 20 years or more may be needed to detect significant
      changes in response variables that are due to MPA implementation. Because of the
      high spatial and temporal variability of fish recruitment patterns, long-term
      monitoring is needed to identify positive responses of fishes to protection in
      the diverse set of habitats in a dynamic eastern boundary current. Qualitative
      estimates of response variables, such as would be obtained from an expert opinion
      process, are unlikely to provide an accurate description of MPA performance.
      Similarly, using one species or one MPA as an indicator is unlikely to provide
      sufficient resolution to accurately describe the performance of multiple MPAs.

PMID- 25760857
TI  - Examining the feasibility of clinical grade CD271+ enrichment of mesenchymal
      stromal cells for bone regeneration.
AB  - INTRODUCTION: Current clinical trials utilize mesenchymal stromal cells (MSCs)
      expanded in culture, however these interventions carry considerable costs and
      concerns pertaining to culture-induced losses of potency. This study assessed the
      feasibility of new clinical-grade technology to obtain uncultured MSC isolates
      from three human intra-osseous tissue sources based on immunomagnetic selection
      for CD271-positive cells. MATERIALS AND METHODS: MSCs were isolated from bone
      marrow (BM) aspirates or surgical waste materials; enzymatically digested femoral
      heads (FHs) and reamer irrigator aspirator (RIA) waste fluids. Flow cytometry for
      the CD45-/lowCD73+CD271+ phenotype was used to evaluate uncultured MSCs before
      and after selection, and to measure MSC enrichment in parallel to colony forming
      unit fibroblast assay. Trilineage differentiation assays and quantitative
      polymerase chain-reaction for key transcripts involved in bone regeneration was
      used to assess the functional utility of isolated cells for bone repair. RESULTS:
      Uncultured CD45-/lowCD271+ MSCs uniformly expressed CD73, CD90 and CD105 but
      showed variable expression of MSCA-1 and SUSD2 (BM>RIA>FH). MSCs were enriched
      over 150-fold from BM aspirates and RIA fluids, whereas the highest MSC purities
      were obtained from FH digests. Enriched fractions expressed increased levels of
      BMP-2, COL1A2, VEGFC, SPARC and CXCL12 transcripts (BM>RIA>FH), with the highest
      up-regulation detected for CXCL12 in BM (>1300-fold). Following culture
      expansion, CD271-selected MSCS were tri-potential and phenotypically identical to
      plastic adherence-selected MSCs. DISCUSSION: A CD271-based GMP-compliant
      immunomagnetic selection resulted in a substantial increase in MSC purity and
      elevated expression of transcripts involved in bone formation, vascularisation
      and chemo-attraction. Although this technology, particularly from RIA fluids, can
      be immediately applied by orthopaedic surgeons as autologous therapy, further
      improvements in MSC purities and pre-clinical testing of product safety would be
      required to develop this process for allogeneic applications.

PMID- 25760858
TI  - Assessment of habitat representation across a network of marine protected areas
      with implications for the spatial design of monitoring.
AB  - Networks of marine protected areas (MPAs) are being adopted globally to protect
      ecosystems and supplement fisheries management. The state of California recently
      implemented a coast-wide network of MPAs, a statewide seafloor mapping program,
      and ecological characterizations of species and ecosystems targeted for
      protection by the network. The main goals of this study were to use these data to
      evaluate how well seafloor features, as proxies for habitats, are represented and
      replicated across an MPA network and how well ecological surveys representatively
      sampled fish habitats inside MPAs and adjacent reference sites. Seafloor data
      were classified into broad substrate categories (rock and sediment) and finer
      scale geomorphic classifications standard to marine classification schemes using
      surface analyses (slope, ruggedness, etc.) done on the digital elevation model
      derived from multibeam bathymetry data. These classifications were then used to
      evaluate the representation and replication of seafloor structure within the MPAs
      and across the ecological surveys. Both the broad substrate categories and the
      finer scale geomorphic features were proportionately represented for many of the
      classes with deviations of 1-6% and 0-7%, respectively. Within MPAs, however,
      representation of seafloor features differed markedly from original estimates,
      with differences ranging up to 28%. Seafloor structure in the biological
      monitoring design had mismatches between sampling in the MPAs and their
      corresponding reference sites and some seafloor structure classes were missed
      entirely. The geomorphic variables derived from multibeam bathymetry data for
      these analyses are known determinants of the distribution and abundance of marine
      species and for coastal marine biodiversity. Thus, analyses like those performed
      in this study can be a valuable initial method of evaluating and predicting the
      conservation value of MPAs across a regional network. 

PMID- 25760866
TI  - Evaluation of urinary interleukin-8 levels in patients with spinal cord injury.
AB  - BACKGROUND: Interleukins are a group of cytokines responsible for regulating
      inflammatory and infectious responses. Interleukin-8 plays an important role in
      chemotaxis and functioning of leukocytes and is locally produced in infected
      tissues; it is seen in abundance in the urine of individuals with Urinary Tract
      Infection. MATERIAL & METHODS: Midstream sterile urine sampling was performed in
      different patients admitted to the Spinal Cord Injury (SCI) research center. The
      samples were tested to determine the level of IL-8 through the ELISA method. The
      commercial kit used for this study was an R & D kit built in Germany. RESULTS:
      The mean level of IL-8 was 369.59 pg/ml and 75.42 pg/ml in male and female
      patients respectively. Among the 97 patients under study, 87 (89.7%) were IL-8
      positive (>10 pg/ml) and 10 patients were IL-8 negative (<10 pg/ml). Among the 87
      IL-8 positive subjects, 64 patients had no UTI symptoms, while 23 did.
      CONCLUSION: SCI patients should have their urinary IL-8 levels measured on a
      routine and periodic basis, irrespective of their SCI severity or the presence or
      absence of UTI symptoms. The timely and effective diagnosis & treatment of UTI
      can prevent the irreversible complications caused by frequent UTI and resistance
      to treatment in this group of patients.

PMID- 25760867
TI  - Saltmarsh boundary modulates dispersal of mangrove propagules: implications for
      mangrove migration with sea-level rise.
AB  - Few studies have empirically examined the suite of mechanisms that underlie the
      distributional shifts displayed by organisms in response to changing climatic
      condition. Mangrove forests are expected to move inland as sea-level rises,
      encroaching on saltmarsh plants inhabiting higher elevations. Mangrove propagules
      are transported by tidal waters and propagule dispersal is likely modified upon
      encountering the mangrove-saltmarsh ecotone, the implications of which are poorly
      known. Here, using an experimental approach, we record landward and seaward
      dispersal and subsequent establishment of mangrove propagules that encounter
      biotic boundaries composed of two types of saltmarsh taxa: succulents and
      grasses. Our findings revealed that propagules emplaced within saltmarsh
      vegetation immediately landward of the extant mangrove fringe boundary frequently
      dispersed in the seaward direction. However, propagules moved seaward less
      frequently and over shorter distances upon encountering boundaries composed of
      saltmarsh grasses versus succulents. We uniquely confirmed that the small subset
      of propagules dispersing landward displayed proportionately higher establishment
      success than those transported seaward. Although impacts of ecotones on plant
      dispersal have rarely been investigated in situ, our experimental results
      indicate that the interplay between tidal transport and physical attributes of
      saltmarsh vegetation influence boundary permeability to propagules, thereby
      directing the initial phase of shifting mangrove distributions. The incorporation
      of tidal inundation information and detailed data on landscape features, such as
      the structure of saltmarsh vegetation at mangrove boundaries, should improve the
      accuracy of models that are being developed to forecast mangrove distributional
      shifts in response to sea-level rise. 

PMID- 25760868
TI  - Dealing with trade-offs in destructive sampling designs for occupancy surveys.
AB  - Occupancy surveys should be designed to minimise false absences. This is commonly
      achieved by increasing replication or increasing the efficiency of surveys. In
      the case of destructive sampling designs, in which searches of individual
      microhabitats represent the repeat surveys, minimising false absences leads to an
      inherent trade-off. Surveyors can sample more low quality microhabitats, bearing
      the resultant financial costs and producing wider-spread impacts, or they can
      target high quality microhabitats were the focal species is more likely to be
      found and risk more severe impacts on local habitat quality. We show how this
      trade-off can be solved with a decision-theoretic approach, using the Millewa
      Skink Hemiergis millewae from southern Australia as a case study. Hemiergis
      millewae is an endangered reptile that is best detected using destructive
      sampling of grass hummocks. Within sites that were known to be occupied by H.
      millewae, logistic regression modelling revealed that lizards were more
      frequently detected in large hummocks. If this model is an accurate
      representation of the detection process, searching large hummocks is more
      efficient and requires less replication, but this strategy also entails
      destruction of the best microhabitats for the species. We developed an
      optimisation tool to calculate the minimum combination of the number and size of
      hummocks to search to achieve a given cumulative probability of detecting the
      species at a site, incorporating weights to reflect the sensitivity of the
      results to a surveyor's priorities. The optimisation showed that placing high
      weight on minimising volume necessitates impractical replication, whereas placing
      high weight on minimising replication requires searching very large hummocks
      which are less common and may be vital for H. millewae. While destructive
      sampling methods are sometimes necessary, surveyors must be conscious of the
      ecological impacts of these methods. This study provides a simple tool for
      identifying sampling strategies that minimise those impacts. 

PMID- 25760869
TI  - Ionotropic Cross-linked Carbo-protein Micro Matrix System: An Approach for
      Improvement of Drug Release, Compaction and Tableting behavior of Losartan
      Potassium.
AB  - The aim of the present research work is to develop carbo-protein polymeric
      complex based sustain release microspheres of losartan potassium and investigate
      the ability of this dosage form to improve the flowability, compressibility and
      tableting properties of losartan potassium. The influence of silk sericin,
      alginate and its blend on various physicochemical parameters and in vitro drug
      release pattern were studied to optimize the concentration of polymeric blend
      required for 12 h. sustain release. Optimized batch was subjected to different
      flowability, compressibility and tableting properties studies to observe the
      effects of carbo-protein microspheres on flow properties. Results indicated that
      the concentration of sericin was found to be the main influential factor for
      prolonged drug release. Different micromeritic studies revealed that the poor
      flowability and compressibility properties of pure losartan potassium were
      significantly improved by this algino-sericin microspheric dosage form. Research
      findings also revealed that plasticity, die filling behavior and tableting
      properties of the pure drug were significantly improved by this microsphere
      formulation. So these prospective results concluded that carbo-protein polymeric
      microspheres helps to sustain the drug release for prolong hours as well as
      improve the flowability, compressibility and tableting properties of losartan
      potassium.

PMID- 25760870
TI  - Oxidized carbon nitrides: water-dispersible, atomically thin carbon nitride-based
      nanodots and their performances as bioimaging probes.
AB  - Three-dimensional (3D) carbon nitride (C3 N4 )-based materials show excellent
      performance in a wide range of applications because of their suitable band
      structures. To realize the great promise of two-dimensional (2D) allotropes of
      various 3D materials, it is highly important to develop routes for the production
      of 2D C3 N4 materials, which are one-atom thick, in order to understand their
      intrinsic properties and identify their possible applications. In this work,
      water-dispersible, atomically thin, and small carbon nitride nanodots were
      produced using the chemical oxidation of graphitic C3 N4 . Various analyses,
      including X-ray diffraction, X-ray photoelectron, Fourier-transform infrared
      spectroscopy, and combustion-based elemental analysis, and thermogravimetric
      analysis, confirmed the production of 3D oxidized C3 N4 materials. The 2D C3 N4
      nanodots were successfully exfoliated as individual single layers; their lateral
      dimension was several tens of nanometers. They showed strong photoluminescence in
      the visible region as well as excellent performances as cell-imaging probes in an
      in vitro study using confocal fluorescence microscopy. 

PMID- 25760872
TI  - Ever-expanding clinical implications of QT interval prolongation.

PMID- 25760871
TI  - Programmed cell death in plants: A chloroplastic connection.
AB  - Programmed cell death (PCD) is an integral cellular program by which targeted
      cells culminate to demise under certain developmental and pathological
      conditions. It is essential for controlling cell number, removing unwanted
      diseased or damaged cells and maintaining the cellular homeostasis. The details
      of PCD process has been very well elucidated and characterized in animals but
      similar understanding of the process in plants has not been achieved rather the
      field is still in its infancy that sees some sporadic reports every now and then.
      The plants have 2 energy generating sub-cellular organelles- mitochondria and
      chloroplasts unlike animals that just have mitochondria. The presence of
      chloroplast as an additional energy transducing and ROS generating compartment in
      a plant cell inclines to advocate the involvement of chloroplasts in PCD
      execution process. As chloroplasts are supposed to be progenies of unicellular
      photosynthetic organisms that evolved as a result of endosymbiosis, the
      possibility of retaining some of the components involved in bacterial PCD by
      chloroplasts cannot be ruled out. Despite several excellent reviews on PCD in
      plants, there is a void on an update of information at a place on the regulation
      of PCD by chloroplast. This review has been written to provide an update on the
      information supporting the involvement of chloroplast in PCD process and the
      possible future course of the field. 

PMID- 25760873
TI  - Risk scores do not adjust for aggressive, evidence-based changes in percutaneous
      coronary intervention practice patterns.
AB  - AIM: Public reporting of procedural outcomes leads to risk averse behavior
      because physicians do not believe the scores account for patient risk. We
      investigated the effects of more aggressive percutaneous coronary intervention
      (PCI) practice on risk-adjusted mortality. METHODS & RESULTS: 8935 PCI were
      performed. Risk adjustment was performed with the New York State PCI risk score.
      The cohort was divided into two eras based on programs implemented to promote
      more aggressive care. Between eras, overall adjusted mortality ratios rose from
      0.66 to 0.90 (observed/predicted, p = 0.02), despite evidence supporting
      consistent procedural quality. CONCLUSION: Evidence-based changes in PCI practice
      were associated with worsening risk-adjusted procedural mortality. These data are
      consistent with physician beliefs regarding risk-adjusted outcome measures.

PMID- 25760874
TI  - Rivaroxaban in atrial fibrillation cardioversion: insights from the X-VeRT trial.
AB  - ABSTRACT  Vitamin K antagonists (VKAs) have traditionally been the standard of
      care for the thromboprophylactic anticoagulation of patients with nonvalvular
      atrial fibrillation (NVAF) undergoing cardioversion. X-VeRT was the first
      prospective trial to explore the safety and efficacy of one of the non-VKA oral
      anticoagulants, rivaroxaban, compared with dose-adjusted VKA as
      thromboprophylaxis in patients with NVAF scheduled to undergo cardioversion. The
      protocol allowed either early (1-5 days) or delayed (3-8 weeks) cardioversion to
      be performed. Rivaroxaban use (20 mg once daily or 15 mg if creatinine clearance
      was 30-49 ml/min) was associated with a similar incidence of adverse
      cardiovascular events and bleeding as VKA use; however, rivaroxaban significantly
      reduced the time to cardioversion in those undergoing delayed cardioversion.
      Thus, rivaroxaban is a safe alternative to VKAs for thromboprophylaxis in
      patients with NVAF undergoing elective cardioversion. 

PMID- 25760875
TI  - Transcatheter mitral valve repair therapies for primary and secondary mitral
      regurgitation.
AB  - Mitral regurgitation is one of the most prevalent valvular heart diseases and its
      prevalence is related to population aging. Elderly patients with age-associated
      co-morbidities have an increased risk for conventional mitral valve surgery.
      Transcatheter mitral valve repair has emerged as a feasible and safe alternative
      in patients with contraindications for surgery or high operative risk. Several
      transcatheter mitral repair technologies have been developed during the last
      decade. While the development of some devices was abandoned due to suboptimal
      results, others demonstrated to be safe and effective and have been included in
      current practice guidelines. Not all technologies are suitable for all mitral
      anatomies and regurgitation mechanisms. Therefore, accurate evaluation of mitral
      valve anatomy and function are pivotal to the success of these therapies. Cardiac
      imaging plays a central role in selecting patients, guiding the procedure and
      evaluating the durability of the repair at follow-up.

PMID- 25760876
TI  - Cardiothoracic ratio for prediction of left ventricular dilation: a systematic
      review and pooled analysis.
AB  - Increased cardiothoracic ratio noted on chest radiographs often prompts concern
      and further evaluation with additional imaging. This study pools available data
      assessing the utility of cardiothoracic ratio in predicting left ventricular
      dilation. A systematic review of the literature was conducted to identify studies
      comparing cardiothoracic ratio by chest x-ray to left ventricular dilation by
      echocardiography. Electronic databases were used to identify studies which were
      then assessed for quality and bias, with those with adequate quality and minimal
      bias ultimately being included in the pooled analysis. The pooled data were used
      to determine the sensitivity, specificity, positive predictive value and negative
      predictive value of cardiomegaly in predicting left ventricular dilation. A total
      of six studies consisting of 466 patients were included in this analysis.
      Cardiothoracic ratio had 83.3% sensitivity, 45.4% specificity, 43.5% positive
      predictive value and 82.7% negative predictive value. When a secondary analysis
      was conducted with a pediatric study excluded, a total of five studies consisting
      of 371 patients were included. Cardiothoracic ratio had 86.2% sensitivity, 25.2%
      specificity, 42.5% positive predictive value and 74.0% negative predictive value.
      Cardiothoracic ratio as determined by chest radiograph is sensitive but not
      specific for identifying left ventricular dilation. Cardiothoracic ratio also has
      a strong negative predictive value for identifying left ventricular dilation.

PMID- 25760878
TI  - Drug therapy for the patient with resistant hypertension.
AB  - Resistant hypertension is associated with high morbidity and mortality. Resistant
      hypertension is defined as blood pressure above targets despite treatment with at
      least three antihypertensive drugs in adequate dose and combination. Nonadherence
      is a frequent cause of uncontrolled hypertension and can be improved by providing
      fixed dose (of two or three agents) single pill combination. Triple combination
      of the most widely used antihypertensive agents (renin-angiotensin-aldosterone
      system antagonists, calcium channel blockers and diuretics) is a safe and
      effective therapy. Fourth line therapy is the use of an aldosterone antagonist.
      Renal denervation and baroreceptor stimulation can be considered in patients who
      remained uncontrolled despite optimal medical therapy.

PMID- 25760879
TI  - Evidence-based diuretics: focus on chlorthalidone and indapamide.
AB  - Thiazide and thiazide-like diuretics are cornerstone treatments for hypertension.
      However, unlike chlorthalidone (CTD) and indapamide (IDP), hydrochlorothiazide
      (HCTZ) lacks evidence for reducing morbidity and mortality as monotherapy
      compared with placebo or control. Despite this fact, HCTZ is prescribed much more
      frequently than CTD or IDP. We believe that all hypertension guidelines should
      follow the National Institute for Health and Excellence (NICE) and make IDP and
      CTD first choice 'thiazide-like diuretics.' This article will focus on the
      available evidence pertaining to HCTZ versus CTD and IDP. We will review the
      pharmacological differences between these three diuretics, as well as the
      clinical trial data and important side effects.

PMID- 25760877
TI  - Priming the proteasome by protein kinase G: a novel cardioprotective mechanism of
      sildenafil.
AB  - The proteasome mediates the degradation of most cellular proteins including
      misfolded proteins, pivotal to intracellular protein hemostasis. Proteasome
      functional insufficiency is implicated in a large subset of human failing hearts.
      Experimental studies have established proteasome functional insufficiency as a
      major pathogenic factor, rationalizing proteasome enhancement as a potentially
      new therapeutic strategy for congestive heart failure. Protein kinase G
      activation known to be cardioprotective was recently found to facilitate
      proteasomal degradation of misfolded proteins in cardiomyocytes; sildenafil was
      shown to activate myocardial protein kinase G, improve cardiac protein quality
      control and slow down the progression of cardiac proteinopathy in mice. This
      identifies the first clinically used drug that is capable of benign proteasome
      enhancement and unveils a potentially novel cardioprotective mechanism for
      sildenafil.

PMID- 25760880
TI  - Continued expansion of the Heart Team concept.
AB  - The concept of a multidisciplinary Heart Team approach to treating cardiovascular
      disease has garnered increasing interest in recent years. This team-based
      approach has been a cornerstone of practice in other medical fields, such as
      oncology and solid organ transplantation. Advances in technology and new
      therapeutic strategies now offer multiple treatment options to patients with
      complex coronary artery or valvular heart disease, making therapeutic decision
      making more challenging. There is a growing literature that use of a Heart Team
      for management of these complex cardiovascular diseases has demonstrated great
      merit. While the composition and implementation of Heart Team will vary, this
      multidisciplinary team-based approach will become the standard of care in
      cardiovascular medicine in the future.

PMID- 25760882
TI  - Erratum.

PMID- 25760881
TI  - Microvascular angina: an update on diagnosis and treatment.
AB  - Many patients with chest pain who are relieved to learn that they have no
      obstructive stenoses at diagnostic angiography are misclassified as having
      noncardiac chest pain. Only recently have we developed the conceptual framework
      and diagnostic tools to understand that ischemic heart disease is not exclusively
      caused by obstructive coronary artery disease, but often has its origin in the
      microcirculation. This article will focus on the diagnosis and treatment of
      microvascular angina as a cause of myocardial ischemia in patients with abnormal
      but 'normal appearing' coronary arteries.

PMID- 25760883
TI  - Corrigendum.

PMID- 25760884
TI  - Serum osteopontin predicts degree of hepatic fibrosis and serves as a biomarker
      in patients with hepatitis C virus infection.
AB  - BACKGROUND & AIMS: Osteopontin (OPN) is a matricellular protein that upregulates
      during pathogenesis of hepatic fibrosis. The present study was aimed to evaluate
      whether serum OPN could be used as a biomarker to assess the degree of hepatic
      fibrosis in patients with hepatitis C virus (HCV) infection. METHODS: Needle
      biopsy was performed on HCV patients and scored as zero fibrosis (F0), mild
      fibrosis (F1), moderate fibrosis (F2), severe fibrosis (F3) and liver cirrhosis
      (F4) based on Masson's trichrome and alpha-smooth muscle actin (alpha-SMA)
      staining. Serum OPN levels were measured using ELISA and correlated with the
      degree of fibrosis. Furthermore, the OPN values were correlated and evaluated
      with platelets count, serum hyaluronic acid (HA), and collagen type IV and
      subjected to receiver operating characteristic (ROC) curve analysis. RESULTS:
      Serum OPN levels were remarkably increased from F0 through F4 in a progressive
      manner and the differences were significant (P < 0.001) between each group. The
      data were highly correlated with the degree of hepatic fibrosis. The ROC curve
      analysis depicted that serum OPN is an independent risk factor and an excellent
      biomarker and a prognostic index in HCV patients. CONCLUSIONS: The results of the
      present study indicate that serum OPN levels reflect the degree of hepatic
      fibrosis and could be used as a biomarker to assess the stage of fibrosis in HCV
      patients which would help to reduce the number of liver biopsies. Furthermore,
      serum OPN serves as a prognostic index towards the progression of hepatic
      fibrosis to cirrhosis and hepatocellular carcinoma.

PMID- 25760885
TI  - A CBCT atlas of buccal cortical bone thickness in interradicular spaces.
AB  - OBJECTIVE: To provide a road map of buccal cortical bone thickness in
      interradicular locations where miniscrew implants are commonly placed. MATERIALS
      AND METHODS: Cone-beam computed tomography images from 100 study quadrants (50
      maxillary and 50 mandibular) were studied. Cortical bone thickness was measured
      at the most mesial point, the midpoint, and the most distal point in
      interradicular areas from the canine to the first molar in both arches at 4 mm
      and 6 mm from the alveolar ridge. Indicator variables of whether the cortical
      bone thickness was thinner than 1 mm and thicker than 1.5 mm were constructed and
      analyzed in a general linear mixed model. RESULTS: Buccal cortical bone was
      significantly thinner at a point bisecting two teeth than the bone adjacent to
      the teeth (P < .0001). The site with the greatest percentage of measurements <1
      mm (20%) was at the midpoint bisecting the mandibular canine and the first
      premolar. The site with the highest percentage of measurements >1.5 mm (50%) was
      in the mandible adjacent to the first molar (distal to the midpoint of the second
      premolar and first molar) at 6 mm from the alveolar crest. CONCLUSION: Cortical
      bone thickness is significantly thinner centrally between two teeth than in the
      areas adjacent to the roots.

PMID- 25760886
TI  - The effect of changes in primary attending doctor coverage frequency on
      orthodontic treatment time and results.
AB  - OBJECTIVE: To determine whether changes in primary attending (PA) doctor coverage
      frequency caused an increase in orthodontic treatment time or a decrease in the
      quality of treatment results in a postgraduate orthodontic clinic. The effect of
      T1 Peer Assessment Rating (PAR) scores on PA doctor coverage frequency, treatment
      times, and results was also evaluated. MATERIALS AND METHODS: A sample of 191
      postorthodontic subjects was divided into three groups based on PA doctor
      coverage (high, medium, or low). Treatment times, treatment results, and other
      variables were compared between the three PA coverage groups. Additionally, the
      sample was divided into three groups based on T1 PAR scores. Attending coverage
      frequency, treatment times, and results were compared between the T1 PAR groups.
      RESULTS: No statistically significant differences were found in treatment time (P
      =  .128) or results (P  =  .052). There were no statistically significant
      differences in the mean scores for T1 PAR (P  =  .056), T2 PAR (P  =  .602),
      patient age at T1 (P  =  .747), total appointments (P  =  .128), missed
      appointments (P  =  .177), or cancelled appointments (P  =  .183). Statistically
      significant differences were found between the low T1 PAR group and the medium
      and high T1 PAR groups (attending coverage, P  =  .008; results, P < .001;
      treatment time, P  =  .001). CONCLUSIONS: Under the conditions of this study,
      variations in PA doctor coverage frequency did not lengthen orthodontic treatment
      or reduce the quality of treatment results. Low T1 PAR scores were associated
      with less PA coverage, less change in PAR, and shorter treatment times.

PMID- 25760887
TI  - Clinical effect of reducing curing times with high-intensity LED lights.
AB  - OBJECTIVE: To evaluate the clinical performance of brackets cured with a high
      intensity, light-emitting diode (LED) with a shorter curing time. MATERIALS AND
      METHODS: Thirty-four patients and a total of 680 brackets were examined using a
      randomized split-mouth design. The maxillary right and mandibular left quadrants
      were cured for 6 seconds with a high-intensity LED light (3200 mW/cm(2)) and the
      maxillary left and mandibular right quadrants were cured for 20 seconds with a
      standard-intensity LED light (1200 mW/cm(2)). Alternating patients had the
      quadrants inverted for the curing protocol. The number and date of each first
      time bracket failure was recorded from 199 to 585 days posttreatment. RESULTS:
      The bracket failure rate was 1.18% for both curing methods. The proportion of
      bracket failure was not significantly different between curing methods (P  = 
      1.000), genders (P  =  1.000), jaws (P  =  .725), sides (P  =  .725), or
      quadrants (P  =  .547). Posterior teeth exhibited a greater proportion of
      failures (2.21%) relative to anterior teeth (0.49%), although the difference was
      not statistically significant (P  =  .065). CONCLUSIONS: No difference was found
      in bond failure rates between the two curing methods. Both methods showed bond
      failure rates low enough to be considered clinically sufficient. The high
      intensity LED light used with a shorter curing time may be considered an
      advantage due to the reduced chair time.

PMID- 25760888
TI  - Protonated rhodosemiquinone at the Q(B) binding site of the M265IT mutant
      reaction center of photosynthetic bacterium Rhodobacter sphaeroides.
AB  - The second electron transfer from primary ubiquinone Q(A) to secondary ubiquinone
      Q(B) in the reaction center (RC) from Rhodobacter sphaeroides involves a
      protonated Q(B)(-) intermediate state whose low pK(a) makes direct observation
      impossible. Here, we replaced the native ubiquinone with low-potential
      rhodoquinone at the Q(B) binding site of the M265IT mutant RC. Because the in
      situ midpoint redox potential of Q(A) of this mutant was lowered approximately
      the same extent (~100 mV) as that of Q(B) upon exchange of ubiquinone with low
      potential rhodoquinone, the inter-quinone (Q(A) -> Q(B)) electron transfer became
      energetically favorable. After subsequent saturating flash excitations, a period
      of two damped oscillations of the protonated rhodosemiquinone was observed. The
      Q(B)H(*) was identified by (1) the characteristic band at 420 nm of the
      absorption spectrum after the second flash and (2) weaker damping of the
      oscillation at 420 nm (due to the neutral form) than at 460 nm (attributed to the
      anionic form). The appearance of the neutral semiquinone was restricted to the
      acidic pH range, indicating a functional pK(a) of <5.5, slightly higher than that
      of the native ubisemiquinone (pK(a) < 4.5) at pH 7. The analysis of the pH and
      temperature dependencies of the rates of the second electron transfer supports
      the concept of the pH-dependent pK(a) of the semiquinone at the Q(B) binding
      site. The local electrostatic potential is severely modified by the strongly
      interacting neighboring acidic cluster, and the pK(a) of the semiquinone is in
      the middle of the pH range of the complex titration. The kinetic and
      thermodynamic data are discussed according to the proton-activated electron
      transfer mechanism combined with the pH-dependent functional pK(a) of the
      semiquinone at the Q(B) site of the RC.

PMID- 25760889
TI  - Energetics and structural evolution of Na-Ca exchanged zeolite A during heating.
AB  - The properties of zeolite A change significantly upon sodium-calcium exchange.
      The impact of cation composition on the temperature-induced phase transformations
      and energetics of Na-Ca exchanged zeolite A was studied systematically using
      powder X-ray diffraction (XRD), thermogravimetric analysis (TGA), differential
      scanning calorimetry (DSC) and high-temperature oxide melt solution calorimetry.
      As the temperature increases, the structural evolution of each Na-Ca exchanged
      zeolite A sample undergoes three distinct stages - dehydration, amorphization,
      and densification/recrystallization. Initially complete dehydration does not
      result in framework degradation, but further heating leads to zeolite phase
      degradation into other aluminosilicate phases. Both amorphization and
      recrystallization shift to higher temperatures as the calcium content increases.
      On the other hand, the enthalpies of formation for the high temperature
      aluminosilicate phases, the amorphous phase (AP) and the dense phase (DP), appear
      to be a linear function of calcium content (average ionic potential) with
      diminishing of energetic stability upon increasing the Ca content. 100% Na-A
      heated at 1200  degrees C has the most exothermic enthalpy of formation from
      oxides (-65.87 +/- 0.87 kJ mol(-1)- TO2), while 97.9% CaNa-A heated at 945 
      degrees C has the least exothermic value (-5.26 +/- 0.62 kJ mol(-1)- TO2). For
      different aluminosilicates with the same chemical composition, the dense phase
      (DP) assemblage is more stable than the amorphous phase (AP). 

PMID- 25760890
TI  - Synthesis, guest binding, and metal coordination of functionalized self-folding
      deep cavitands.
AB  - A simple method to introduce donor functions to the upper rim of self-folding
      benzimidazole-based deep cavitands is described. The upper rim donors allow
      controlled noncovalent binding of suitably sized guest species via both self
      complementary hydrogen bonding and space-filling interactions, and metal-mediated
      self-folding is possible if bidentate coordinators are incorporated. 

PMID- 25760891
TI  - Tracing formation and durability of calcite in a Punic-Roman cistern mortar
      (Pantelleria Island, Italy).
AB  - Ancient hydraulic lime mortar preserves chemical and isotopic signatures that
      provide important information about historical processing and its durability. The
      distribution and isotopic composition of calcite in a mortar of a well-preserved
      Punic-Roman cistern at Pantelleria Island (Italy) was used to trace the formation
      conditions, durability, and individual processing periods of the cistern mortar.
      The analyses of stable carbon and oxygen isotopes of calcite revealed four
      individual horizons, D, E, B-1 and B-2, of mortar from the top to the bottom of
      the cistern floor. Volcanic and ceramic aggregates were used for the production
      of the mortar of horizons E/D and B-1/B-2, respectively. All horizons comprise
      hydraulic lime mortar characterized by a mean cementation index of 1.5 +/- 1, and
      a constant binder to aggregate ratio of 0.31 +/- 0.01. This suggests standardized
      and highly effective processing of the cistern. The high durability of calcite
      formed during carbonation of slaked lime within the matrix of the ancient mortar,
      and thus the excellent resistance of the hydraulic lime mortar against water, was
      documented by (i) a distinct positive correlation of delta(18)Ocalcite and
      delta(13)Ccalcite; typical for carbonation through a mortar horizon, (ii) a
      characteristic evolution of delta(18)Ocalcite and delta(13)Ccalcite through each
      of the four mortar horizons; lighter follow heavier isotopic values from upper to
      lower part of the cistern floor, and (iii) delta(18)Ocalcite varying from -10 to 
      5 0/00 Vienna Pee Dee belemnite (VPDB). The range of delta(18)Ocalcite values
      rule out recrystallization and/or neoformation of calcite through chemical attack
      of water stored in cistern. The combined studies of the chemical composition of
      the binder and the isotopic composition of the calcite in an ancient mortar
      provide powerful tools for elucidating the ancient techniques and processing
      periods. This approach helps to evaluate the durability of primary calcite and
      demonstrates the importance of calcite as a proxy for chemical attack and quality
      of the ancient inorganic binder.

PMID- 25760894
TI  - Site preference of NH3-adsorption on Co, Pt and CoPt surfaces: the role of charge
      transfer, magnetism and strain.
AB  - Oxidation of Co at the surface poses a major problem in the cyclable use of CoPt,
      a cost-effective catalyst for proton exchange membrane fuel cells. This can be
      alleviated by attaching a ligand selectively to Co-sites to stop its oxidation
      without compromising the catalytic activity. Here, we present a comparative
      analysis of adsorption of NH3 on the (0001) surface of Co in the HCP structure
      and (111) surfaces of Pt and CoPt alloy in the FCC structure, using first
      principles density functional theoretical calculations. While NH3 binds more
      strongly with the Pt surface than with the Co surface, we find that its binding
      with the Co atom is stronger than that with the Pt atom on the surface of the
      CoPt alloy. Our analysis of the charge density and electronic structure shows how
      this originates from (a) the electron transfer from the minority spin d-band of
      Co to Pt, and (b) shift in the energy of d-bands and the magnetic moments of Co
      atoms on the surface of the CoPt alloy relative to those on the (0001) surface of
      Co. Hybridization of the d-states of Co in CoPt with pz states of N in NH3 used
      to stop Co oxidation also results in improving the charge transfer from Co to Pt
      that is relevant to the catalytic activity of CoPt. We finally present the
      analysis of how the interaction of NH3 with the CoPt surface can be tuned with
      strain. 

PMID- 25760892
TI  - Tumour necrosis factor-alpha contributes to improved cardiac ischaemic tolerance
      in rats adapted to chronic continuous hypoxia.
AB  - AIM: It has been demonstrated that tumour necrosis factor-alpha (TNF-alpha) via
      its receptor 2 (TNFR2) plays a role in the cardioprotective effects of
      preconditioning. It is also well known that chronic hypoxia is associated with
      activation of inflammatory response. With this background, we hypothesized that
      TNF-alpha signalling may contribute to the improved ischaemic tolerance of
      chronically hypoxic hearts. METHODS: Adult male Wistar rats were kept either at
      room air (normoxic controls) or at continuous normobaric hypoxia (CNH; inspired
      O2 fraction 0.1) for 3 weeks; subgroups of animals were treated with infliximab
      (monoclonal antibody against TNF-alpha; 5 mg kg(-1), i.p., once a week).
      Myocardial levels of oxidative stress markers and the expression of selected
      signalling molecules were analysed. Infarct size (tetrazolium staining) was
      assessed in open-chest rats subjected to acute coronary artery
      occlusion/reperfusion. RESULTS: CNH increased myocardial TNF-alpha level and
      expression of TNFR2; this response was abolished by infliximab treatment. CNH
      reduced myocardial infarct size from 50.8 +/- 4.3% of the area at risk in
      normoxic animals to 35.5 +/- 2.4%. Infliximab abolished the protective effect of
      CNH (44.9 +/- 2.0%). CNH increased the levels of oxidative stress markers (3
      nitrotyrosine and malondialdehyde), the expression of nuclear factor kappaB and
      manganese superoxide dismutase, while these effects were absent in infliximab
      treated animals. CNH-elevated levels of inducible nitric oxide synthase and
      cyclooxygenase 2 were not affected by infliximab. CONCLUSION: TNF-alpha plays a
      role in the induction of ischaemia-resistant cardiac phenotype of CNH rats,
      possibly via the activation of protective redox signalling.

PMID- 25760895
TI  - Diastereoselectively switchable asymmetric haloaminocyclization for the synthesis
      of cyclic sulfamates.
AB  - An asymmetric synthesis of cyclic sulfamates by catalytic haloaminocyclization of
      primary sulfamate ester derivatives is described. The remarkable reversal of
      diastereoselectivity was found to be dependent on the halogen source and the
      chiral catalyst. By using privileged complexes of N,N'-dioxides with Sc(OTf)3 or
      Lu(OTf)3 as the catalyst, a variety of enantioenriched syn- and anti-cyclic
      sulfamates or related trans-aziridines could be obtained in 92-99 % ee and up to
      97 % yield.

PMID- 25760896
TI  - The future of psychiatry as clinical neuroscience: why not now?

PMID- 25760897
TI  - Perception of safety, importance, and effectiveness of vaccinations among urban
      school employees in Utah.
AB  - PURPOSE: School employees are in direct contact with children in confined areas,
      a setting in which communicable infection can quickly spread. Therefore, it is
      important for school employees to be fully vaccinated. The purpose of this study
      is to ascertain the current vaccination status and perceptions of school
      employees in an urban school district. DATA SOURCES: The study employed a
      nonexperimental mixed-method design. School employee participants (N = 1400)
      completed a questionnaire to evaluate vaccination status, availability of
      vaccination records, and vaccination awareness. Participants were randomly
      selected from 85 schools within one urban school district. CONCLUSIONS: Two
      common perceptions about vaccines emerged from the questionnaire: (a) vaccines
      are only for children and (b) vaccinations received during childhood are still
      effective. School employees are unaware of their own vaccination status and the
      recommended vaccination schedule for adults. Additionally, accessibility to
      immunization records for adults is frequently inadequate. IMPLICATIONS FOR
      PRACTICE: Healthcare providers (HCPs), including nurse practitioners (NPs), are
      the first line of defense to ensure adults are adequately vaccinated. When
      vaccinations are tracked and recommended by HCPs, vaccination uptake is improved.
      NPs who discuss recommended vaccinations with adult patients are instrumental in
      improving vaccination rates among school employees.

PMID- 25760900
TI  - Concurrent primary peritoneal low-grade serous carcinoma and endometrial high
      grade serous carcinoma.
AB  - A 64-yr-old postmenopausal woman with high-grade squamous intraepithelial lesion
      and atypical glandular cell of undetermined significance on her Pap test was
      found to have endometrial serous carcinoma (high grade) involving a polyp in a
      subsequent endometrial biopsy. She underwent hysterectomy and bilateral salpingo
      oophorectomy with multiple biopsies of the peritoneum. Microscopic examination of
      the entirely submitted uterus showed no residual serous carcinoma. Multiple foci
      of low-grade serous tumor with extensive calcifications and psammoma bodies were
      identified on the surfaces of the left fallopian tube, ovaries, and biopsies of
      the peritoneum, consistent with peritoneal primary low-grade serous carcinoma. To
      our knowledge, this is the first reported case of low-grade serous carcinoma of
      the peritoneum with a concurrent (high-grade) serous carcinoma of the endometrium
      arising from an endometrial polyp. 

PMID- 25760901
TI  - Primary myxoid liposarcoma of the ovary in a postpartum female: a case report and
      review of literature.
AB  - A 36-year-old gravida 4, para 2 African-American woman, presented at three months
      postpartum with a right ovarian mass identified on a lumbar spine MRI as part of
      a neurology workup for persistent lower back pain. A follow-up pelvic ultrasound
      noted a 7.0 * 6.1 * 3.8 cm septated mixed cystic and solid mass. Exploratory
      laparoscopy and right ovarian cystectomy yielded a final pathologic diagnosis of
      intermediate grade myxoid liposarcoma, confirmed with DDIT3 gene rearrangement
      studies.

PMID- 25760898
TI  - STAT3-Activating Cytokines: A Therapeutic Opportunity for Inflammatory Bowel
      Disease?
AB  - The gastrointestinal tract is lined by a single layer of epithelial cells that
      secrete mucus toward the lumen, which collectively separates the immune sentinels
      in the underlying lamina propria from the intestinal microflora to prevent
      aberrant immune responses. Inflammatory bowel disease (IBD) describes a group of
      autoimmune diseases that arise from defects in epithelial barrier function and,
      as a consequence, aberrant production of inflammatory cytokines. Among these,
      interleukin (IL)-6, IL-11, and IL-22 are elevated in human IBD patients and
      corresponding mouse models and, through activation of the JAK/STAT3 pathway, can
      both propagate and ameliorate disease. In particular, cytokine-mediated
      activation of STAT3 in the epithelial lining cells affords cellular protection,
      survival, and proliferation, thereby affording therapeutic opportunities for the
      prevention and treatment of colitis. In this review, we focus on recent insights
      gained from therapeutic modulation of the activities of IL-6, IL-11, and IL-22 in
      models of IBD and advocate a cautionary approach with these cytokines to minimize
      their tumor-promoting activities on neoplastic epithelium. 

PMID- 25760902
TI  - Pathology of endometrial ablation failures: a clinicopathologic study of 164
      cases.
AB  - Endometrial ablation is a minimally invasive alternative to hysterectomy for
      abnormal uterine bleeding. Although the failure rate is low, continued bleeding
      or development of pelvic pain after ablation does occur. We analyzed the
      clinicopathologic features of 164 hysterectomy specimens after endometrial
      ablation, 19 of which were performed for indications other than failed ablation
      (control cases). Pathologic findings included: dense fibrosis and hyalinization
      of the endometrial surface ablative necrosis within the uterine cavity and
      adherent to the endometrial surface, persistent months after ablation; uterine
      cavity lined by superficial, large, congested, patent blood vessels with
      atherosis; ablation changes present only in the lower uterine segment; and
      residual endometrium present in the cornual regions. Patients with ablative
      necrosis underwent subsequent hysterectomy sooner than those without such debris
      (median of 5 vs. 23 mo, respectively). Patients with superficial abnormal vessels
      were also more likely to have a shorter ablation-hysterectomy interval than those
      without (median of 2 vs. 18 mo, respectively). Patients with associated
      adenomyosis or prior tubal ligation were significantly more likely to have
      continued bleeding. Possible sources of continued abnormal bleeding or pelvic
      pain include: the presence of ablative necrosis or superficial abnormal blood
      vessels, although the association did not reach statistical significance in this
      study; incomplete ablation, affecting only the lower uterine segment or sparing
      the cornual region; tubal endometriosis after ligation; and endometrial
      regeneration via adenomyosis. 

PMID- 25760903
TI  - A Unique Case of Extraovarian Sex-Cord Stromal Fibrosarcoma, With Subsequent
      Relapse of Differentiated Sex-Cord Tumor.
AB  - Primary fibrosarcoma arising from ovarian sex-cord stroma is a very rare
      neoplasm, with only a few reports in the literature. These tumors have been
      reported to express inhibin which allows their distinction from fibrosarcomas of
      soft tissue. Here, we report a case of a fibrosarcoma arising in the broad
      ligament. Despite being totally separate from the ovary, the tumor was diagnosed
      as sex-cord stromal type on the basis of inhibin expression. Furthermore, this
      patient suffered a recurrence of her tumor in the pelvis, which showed both the
      fibrosarcomatous, as well as other sex-cord elements, confirming the sex-cord
      stromal differentiation of the sarcoma. To our knowledge, this is the first case
      of a sex-cord stromal fibrosarcoma arising from an extraovarian site.
      Furthermore, this is also the first case of a recurrent fibrosarcoma, which
      showed redifferentiation of the tumor into other sex-cord components. 

PMID- 25760904
TI  - Ovarian strumal carcinoid containing appendiceal-type mucinous tumor patterns
      presenting as pseudomyxoma peritonei.
AB  - We report for the first time a case of ovarian strumal carcinoid containing both
      trabecular carcinoid and mucinous glands lined by both goblet and neuroendocrine
      cells and a low-grade mucinous neoplasm that presented clinically as pseudomyxoma
      peritonei in the absence of appendiceal lesion in a 58-yr-old woman.
      Histologically, there were both a tall columnar cell epithelial component lacking
      neuroendocrine cells, showing the scalloped contours and subepithelial clefts of
      low-grade appendiceal-type neoplasms and a mixed goblet cell neuroendocrine
      element. Characteristically, both reproduced appendiceal neoplastic phenotypes in
      a teratoid fashion. In addition, we present previously unreported oncocytic and
      mucinous changes in the thyroideal components of strumal carcinoid. This case
      represents a rare instance of pseudomyxoma peritonei of primary ovarian origin
      and is an example of multiple somatic teratoid endodermal differentiations of the
      different sections of the embryonal gut: foregut represented by thyroid, midgut
      by both mucinous appendiceal components, and hindgut by trabecular carcinoid. 

PMID- 25760905
TI  - Pseudoxanthomatous salpingitis as an ex vivo model of fallopian tube serous
      carcinogenesis: a clinicopathologic study of 49 cases.
AB  - Iron is a well-documented carcinogen based on both animal models and
      observational studies in humans. There are limited published data on
      pseudoxanthomatous salpingitis, an uncommon condition characterized by the
      accumulation of histiocytes containing iron and iron-related compounds-lipofuscin
      and hemosiderin-in the lamina propria of the fallopian tube. The clinical and
      pathologic features of 49 consecutive cases were evaluated. The mean patient age
      was 53. A history of endometriosis was found in 20%, infertility in 17%, and
      tubal ligation in 7%. Thirteen (27%) had endometrial cancer and 2 patients had
      prior radiation therapy for cervical carcinoma. Histologic evidence of
      endometriosis other than tubal pigment deposition was identified in 65%, and in
      the fallopian tubes in 35%. Pigment deposition was unilateral in 65% and
      multifocal or diffuse in 80%. Plasma cells, eosinophils, and neutrophils were
      present in the tubal lamina propria in 57%, 18%, and 24%, respectively.
      Hydrosalpinx was present in 51%. An iron stain was positive in pseudoxanthoma
      cells lacking hemosiderin in 14 of 18 cases (78%). By immunohistochemistry, 2 of
      22 cases displayed p53 signatures. The Ki67 proliferation index was elevated
      (>10%) in 11 of 22 cases, with a mean index of 32% in those cases. An elevated
      proliferation index did not correlate with inflammation. In summary, these
      findings characterize the clinical and pathologic features of pseudoxanthomatous
      salpingitis and confirm its close association with endometriosis, occasional
      association with radiation therapy, and the presence of iron in the histiocytes.
      In view of the evolving paradigm shift implicating the fallopian tubal epithelium
      as the site of origin of high-grade extrauterine serous carcinoma, the presence
      of iron and iron-related compounds in the fallopian tube provides an opportunity
      to study the early events in high-grade serous carcinogenesis in a setting
      characterized by a well-documented carcinogen in close anatomic proximity to the
      putative epithelium of origin. 

PMID- 25760906
TI  - Endometrial involvement in pseudomyxoma peritonei secondary to low-grade
      appendiceal mucinous neoplasm: report of 2 cases.
AB  - Pseudomyxoma peritonei is a clinical condition characterized by the presence of
      mucinous ascites, usually with variable amounts of neoplastic enteric-type
      mucinous epithelium, and most commonly secondary to spread from a low-grade
      appendiceal mucinous neoplasm. We report 2 cases of pseudomyxoma peritonei
      associated with low-grade appendiceal mucinous neoplasms where there was
      colonization of the endometrium (both cases) and cervical mucosa (1 case) by low
      grade atypical enteric-type mucinous epithelium (CK20 positive and CK7 negative).
      The patients had symptoms of mucoid vaginal discharge and endometrial biopsies in
      both (1 patient had multiple endometrial biopsies over a period of 11 mo) and
      were initially interpreted as representing mucinous metaplasia. Pseudomyxoma
      peritonei may rarely result in endometrial and cervical mucosal involvement,
      presumably secondary to transtubal spread. 

PMID- 25760907
TI  - Optimal sampling of grossly normal omentum in staging of gynecologic
      malignancies.
AB  - The pathologic detection of microscopic omental metastases is important for the
      staging and treatment of ovarian and endometrial cancer. The question of how to
      sample grossly negative omentectomy specimens has not been adequately answered.
      We reviewed our institutional experience by retrieving a series of gynecologic
      cancer cases from 1998 to 2013 in which the omentum was grossly negative, but
      microscopically positive. There were 21 patients with ovarian carcinoma, 7 with
      ovarian borderline tumors, and 16 with endometrial carcinoma (44 patients in
      total). Cases in which the omentum was grossly abnormal or suspicious were
      excluded. A mean of 5.2 blocks were submitted per case (range, 4-15), of which a
      mean of 2.7 were positive for metastatic disease (range, 1-5). The distribution
      of cases by percentage of blocks positive was bimodal: some cases showed only 1
      or 2 foci of disease in the entire sampled omentum, whereas in other cases nearly
      every block was positive. Only 3 cases had been sampled with >5 blocks. We used a
      series of simulated cases, bootstrapped on the retrospective series, to determine
      the additional sensitivity conferred by submitting >5 blocks. This model
      indicated that 5 blocks will, in fact, be insufficient to capture microscopic
      metastases in some cases. Examination of 5 blocks has an estimated sensitivity of
      82%, whereas submission of 10 blocks raises the sensitivity to 95%. These results
      suggest that submission of 10 blocks should be considered for grossly negative
      omentectomy specimens when other staging is negative. 

PMID- 25760908
TI  - Discrepancies between biopsy-based and excision-based grading of cervical
      intraepithelial neoplasia: the important role of time between excision and
      biopsy.
AB  - We sought to evaluate the rate of cervical intraepithelial neoplasia (CIN) <= 1
      in loop electrosurgical excision procedure (LEEP) specimens after the treatment
      of biopsy-proven CIN 2-3, and to identify factors that are associated with the
      rate of CIN <= 1, especially focusing on the time interval between biopsy and
      LEEP. The goal of this research is to reduce the overtreatment of women with CIN
      2-3. This was a retrospective study performed on women undergoing LEEP for biopsy
      proven CIN 2-3 in Qilu hospital in Shandong, China. Patients were separated
      according to LEEP pathology (CIN <= 1 vs. CIN 2-3), and compared using the chi2
      test and Student t test. The main outcome measures were pathologic discrepancy
      (defined as CIN 2-3 at biopsy, but CIN <= 1 at excision). Of the 391 women with
      biopsy-proven CIN 2-3, 26.9% had LEEP specimens with CIN <= 1 histologies. The
      likelihood of a CIN <= 1 LEEP specimen increases for greater biopsy-LEEP
      intervals (odds ratio, 1.374; 95% confidence interval, 1.089-1.735; P = 0.008).
      Cases in younger women and biopsy-assessed CIN 2 cases were both more likely to
      have CIN 1 or negative LEEP specimens. The rate of spontaneous histologic
      regression (defined as CIN <= 1 at resection) was 26.9%. These low-grade lesions
      were more common in LEEP specimens from young women with CIN 2 at biopsy, and who
      underwent LEEP later after the initial biopsy.

PMID- 25760909
TI  - Osteosarcoma as Malignant Mural Nodule in Ovarian Mucinous Neoplasms of
      Intestinal Type: Report of 2 Cases.
AB  - Mural nodules, which may be benign or malignant, are well recognized in ovarian
      mucinous neoplasms, especially of borderline type. Malignant mural nodules most
      commonly comprise anaplastic carcinoma but sarcomas of various types have been
      reported. We report 2 cases of osteosarcoma occurring in young women (aged 18 and
      34) as malignant mural nodules in a Grade 1 ovarian mucinous carcinoma of
      intestinal type and a borderline mucinous tumor of intestinal type. Primary
      osteosarcomas of the ovary have been described either arising within a teratoma
      or as a pure neoplasm but, to the best of our knowledge, osteosarcoma occurring
      as a mural nodule in an ovarian mucinous neoplasm has not been reported. In both
      our cases, the tumor was Stage 1 at presentation and the patients were treated
      with surgery without adjuvant chemotherapy. Both patients are free of disease
      with follow-up of 12 and 18 mo. 

PMID- 25760910
TI  - Association of annexin A2 with cancer development (Review).
AB  - Annexin A2 (ANXA2) is a well-known calcium-dependent phospholipid binding protein
      widely distributed in the nucleus, cytoplasm and extracellular surface of various
      eukaryotic cells. It has been recognized as a pleiotropic protein affecting a
      wide range of molecular and cellular processes. Dysregulation and abnormal
      expression of ANXA2 are linked to a large number of prevalent diseases, including
      autoimmune and neurodegenerative disease, antiphospholipid syndrome,
      inflammation, diabetes mellitus and a series of cancers. Accumulating data
      suggest that ANXA2 is aberrantly expressed in a wide spectrum of cancers, and
      exerts profound effects on tumor cell adhesion, proliferation, apoptosis,
      invasion and metastasis as well as tumor neovascularization via different modes
      of action. However, despite significant research, our knowledge of the mechanism
      by which ANXA2 participates in cancer development remains fragmented. The present
      review systematically summarizes the effects of ANXA2 on tumor progression, in an
      attempt to gain an improved understanding of the underlying mechanisms and to
      provide a potential effective target for cancer therapy. 

PMID- 25760911
TI  - Rituximab and Acute Retinal Necrosis in a Patient with Scleromalacia and
      Rheumatoid Arthritis.
AB  - BACKGROUND: Rituximab is a widely used biologic agent, which has shown favourable
      results in the treatment of vasculitis. But immunosuppressive treatment also
      bears the risk of severe complications. METHODS: A patient with rheumatoid
      arthritis, progressive scleromalacia, and acute retinal necrosis on therapy with
      rituximab is reported. RESULTS: For the first time, a correlation between
      rituximab and acute retinal necrosis in a patient with progressive rheumatoid
      scleromalacia is shown. CONCLUSIONS: Although rituximab is a promising biologic
      agent for the treatment of autoimmune diseases, it bears the risk of reactivation
      of viral infections, including the onset of acute retinal necrosis.

PMID- 25760912
TI  - Response to the Letter of Dr. Mehmet Agilli et al.: Elevated Plasma Pentraxin3
      Levels and Its Association with Neovascular Age-related Macular Degeneration.

PMID- 25760913
TI  - Microbiologic Examination of Bandage Contact Lenses Used after Corneal Collagen
      Cross-linking Treatment.
AB  - PURPOSE: To investigate the agents of bacterial contamination of contact lenses
      after corneal collagen cross-linking (CCL), and to present the possible changes
      of ocular flora after riboflavin/ultraviolet A. METHODS: Seventy-two contact
      lenses of patients who underwent CCL and 41 contact lenses of patients who
      underwent photorefractive keratectomy (PRK) as control group were enrolled to the
      study. After 48 h of incubation, broth culture media was transferred to plates.
      Samples were accepted as positive if one or more colony-forming units were shown.
      RESULTS: There were positive cultures in 12 (16.7%) contact lenses in the CCL
      group and 5 (12.2%) had positive cultures in PRK group. Coagulase-negative
      staphlycocci (CNS) were the most frequent microorganism. Alpha hemolytic
      streptococci and Diphteroid spp. were the other isolated microorganisms.
      CONCLUSIONS: Bacterial colonization can occur during and early after the CCL
      procedure in epithelial healing. To prevent corneal infections after the
      treatment, prophylactic antibiotics should be prescribed.

PMID- 25760914
TI  - Cytomegalovirus Retinitis in a Human Immunodeficiency Virus-negative Cohort: Long
      term Management and Complications.
AB  - PURPOSE: To examine the clinical outcomes achieved by using intravitreal
      ganciclovir injections combined with systemic anti-viral therapy in treating
      cytomegalovirus (CMV) retinitis in patients without human immunodeficiency virus
      (HIV) infection. METHODS: Twenty-three eyes of 15 HIV-negative patients diagnosed
      with CMV retinitis were included in this retrospective study. RESULTS: The median
      follow-up was 68 weeks (range, 12-156), and median number of injections was 10
      (range, 2-22). The retinal lesions stopped progressing within 1-2 weeks following
      treatment. All of the eyes showed either unchanged or >=2 line improvements of
      BCVA at last visit. There was no development of CMV retinitis in a fellow eye, or
      recurrence in a studied eye. Systemic complications such as neutropenia were not
      detected. CONCLUSIONS: Intravitreal ganciclovir injections combined with systemic
      anti-viral treatment is a good therapeutic option for treating CMV retinitis
      without HIV infection. Such treatment provided favorable visual outcomes, with
      minimal ocular and systemic complications.

PMID- 25760915
TI  - Potential of Pegylated Interferon Alpha-2a in Behcet Uveitis: A Report of Five
      Cases.

PMID- 25760917
TI  - Spectrum of Uveitis in A German Tertiary Center: Review of 474 Consecutive
      Patients.
AB  - PURPOSE: To analyze the spectrum of uveitis at a German tertiary center. PATIENTS
      AND METHODS: A total of 474 consecutive patients with uveitis were classified
      according to the primary anatomic site of inflammation, examined for laterality
      of disease, and screened for etiologies. RESULTS: Out of the total, 253 patients
      (53%) had anterior uveitis, 90 patients (19%) had intermediate uveitis, 100
      patients (21%) had posterior uveitis, and 31 patients (7%) had panuveitis. Fifty
      six percent of the patients had bilateral involvement, predominantly in
      intermediate uveitis (ratio 4:1) and panuveitis (ratio 3.4:1). Regarding the
      etiology of all uveitis cases we found 17% infectious, 23% specific clinical
      entities, 20% associated with systemic disease (most commonly sarcoidosis with
      11%), and 41% idiopathic uveitis. CONCLUSIONS: Anterior uveitis was the most
      common anatomic site of intraocular inflammation. Using a tailored approach,
      screening for systemic etiologies is recommended, since 20% of all patients had
      associated systemic diseases.

PMID- 25760916
TI  - Spectral-domain Optical Coherence Tomography Patterns in Intraocular Lymphoma.
AB  - PURPOSE: To examine spectral-domain optical coherence tomography (SD-OCT)
      patterns in intraocular lymphoma (IOL). METHODS: Records of 13 patients (21 eyes)
      with IOL were retrospectively reviewed. SD-OCT was evaluated at initial visit and
      during follow-up. RESULTS: SD-OCT images at initial visit demonstrated disruption
      of the ellipsoid zone (8 eyes, 38.1%) and hyperreflective nodules at the retinal
      pigment epithelium (RPE) level (5 eyes, 23.8%). During follow-up, disruption of
      the ellipsoid zone (10 eyes, 47.6%) and hyperreflective nodules at the RPE level
      (7 eyes, 33.3%) were noted. In 5 eyes showing hyperreflective nodules at the RPE
      level, the hyperreflective nodules were reduced after treatment with intravitreal
      methotrexate. CONCLUSIONS: Hyperreflective nodules in the outer retina and
      disruption of the ellipsoid zone were observed in nearly one-half of patients
      with IOL over time. SD-OCT may allow for early detection of small macular
      abnormalities and aid in monitoring of treatment efficacy in this disease.

PMID- 25760918
TI  - Clinical Review: Familial Mediterranean Fever-An Overview of Pathogenesis,
      Symptoms, Ocular Manifestations, and Treatment.
AB  - Familial Mediterranean fever is an autoinflammatory multisystem disease, which
      most commonly affects patients from the Mediterranean basin. This review
      discusses the common polymorphisms in the MEFV gene as well as the role of pyrin
      in disease pathogenesis. Patients with familial Mediterranean fever typically
      develop peritonitis, pleuritis, arthritis, and fever. In addition, a number of
      authors have reported ophthalmic features. These case reports and series are
      further explored in this review. Colchicine has transformed the prognosis for
      patients with familial Mediterranean fever. The rationale for the use of
      colchicine, as well as the evidence for newer biologic agents is also covered. 

PMID- 25760919
TI  - Regarding Comments by Yolcu et al. on "Evaluation of Choroidal Thickness in
      Ankylosing Spondylitis Using Optical Coherence Tomography".

PMID- 25760921
TI  - Connecting a sociology of childhood perspective with the study of child health,
      illness and wellbeing: introduction.
AB  - In the last decades we have seen a growing interest in research into children's
      own experiences and understandings of health and illness. This development, we
      would argue, is much stimulated by the sociology of childhood which has drawn our
      attention to how children as a social group are placed and perceived within the
      structure of society, and within inter-generational relations, as well as how
      children are social agents and co-constructors of their social world. Drawing on
      this tradition, we here address some cross-cutting themes that we think are
      important to further the study of child health: situating children within health
      policy, drawing attention to practices around children's health and well-being
      and a focus on children as health actors. The paper contributes to a critical
      analysis of child health policy and notions of child health and normality,
      pointing to theoretical and empirical research potential for the sociology of
      children's health and illness. 

PMID- 25760920
TI  - Ipilimumab-induced Ocular and Orbital Inflammation--A Case Series and Review of
      the Literature.
AB  - PURPOSE: Ipilimumab, a monoclonal antibody directed against the immune protein
      cytotoxic T-lymphocyte antigen-4 (CTLA-4), characteristically induces side
      effects called "immune-related adverse events" (IRAE). Although ophthalmic
      involvement is rare, we report 7 cases of eye and orbit complications related to
      ipilimumab therapy. METHODS: We performed a retrospective review of patients with
      metastatic melanoma who developed ipilimumab-related ocular or orbital
      inflammation who were seen at our institutions. RESULTS: Seven patients were
      identified: 4 patients had orbital inflammation, 2 had uveitis, and 1 had
      peripheral ulcerative keratitis. Four patients developed inflammation after the
      second ipilimumab infusion, 2 after the third infusion and 1 after the first
      infusion. All 4 patients with orbital inflammation were treated with systemic
      corticosteroids. Two patients with uveitis were treated with topical steroids,
      but were also treated with systemic corticosteroids for other IRAE, including
      colitis and hypophysitis. The patient with keratitis was treated with topical
      corticosteroids alone with resolution of inflammation. All 7 patients
      discontinued ipilimumab therapy, 5 due to systemic IRAE and 2 due to tumor
      progression. Five of 7 patients had tumor progression on ipilimumab therapy.
      CONCLUSIONS: Ocular and orbital inflammation may occur in patients with
      metastatic melanoma receiving ipilimumab, is frequently accompanied by other
      IRAEs, and resolves with corticosteroid treatment, often leaving no long-term
      sequelae.

PMID- 25760922
TI  - Where is the child? A discursive exploration of the positioning of children in
      research on mental-health-promoting interventions.
AB  - The present study explores the discursive positioning of children in research
      articles on mental-health-promoting interventions. The questions under
      investigation are: are children positioned as active or passive agents, are
      children's health and wellbeing contextualised, and if so how? How is the child
      perceived; that is, how are age, gender, socioeconomic status, family structure,
      dis/ability, and so on accounted for? We found that the positioning of the child
      as passive and formed by adults prevails; health is largely individualised and
      decontextualised in that it is depicted as being contingent on the person's own
      capabilities. However, there are instances in which children are positioned as
      active subjects, their opinions are in focus, and their health and wellbeing are
      connected to social relations and context. We propose a more active discussion
      about how children and wellbeing are conceptualised in the outlining,
      implementation and research of public health interventions. Moreover, children-
      just like adults--should be increasingly regarded as service users who are
      entitled to have a say in matters that concern them.

PMID- 25760923
TI  - Negotiating pain: the joint construction of a child's bodily sensation.
AB  - Traditional theories of socialisation, in which the child was viewed as a passive
      subject of external influences, are increasingly being rejected in favour of a
      new sociology of childhood which frames the child as a social actor. This article
      demonstrates the way in which conversation analysis can reveal children's agency
      in the micro-detail of naturally occurring episodes in which children express
      bodily sensations and pain in everyday life. Based on 71 video-recordings of
      mealtimes with five families, each with two children under 10 years old, the
      analysis focuses on the components of children's expressions of bodily sensation
      (including pain), the character of parents' responses and the nature of the
      subsequent talk. The findings provide further evidence that children are social
      actors, active in constructing, accepting and resisting the nature of their
      physical experience and pain. A conversation analysis of ordinary family talk
      facilitates a description of how a child's agency is built, maintained or
      resisted through the interactional practices participants employ to display
      knowledge.

PMID- 25760925
TI  - Quantum Chemical Study of Autoignition of Methyl Butanoate.
AB  - Methyl butanoate is a widely studied surrogate for fatty acid esters used in
      biodiesel fuel. Here we report a detailed analysis of the thermodynamics and
      kinetics of the autoignition chemistry of methyl butanoate. We employ composite
      CBS-QB3 calculations to construct the potential energy profiles of radicals
      derived from methyl butanoate. We compare our results with recently published
      G3MP2B3 results for reactions of peroxy (ROO(*)) and hydroperoxy alkyl ((*)QOOH)
      radicals and comment on differences in barrier heights and reaction enthalpies.
      Our emphasis, however, is on hydroperoxy alkylperoxy ((*)OOQOOH) radicals that
      are critical for autoignition of diesel fuel. We examined four classes of
      reactions: peroxy radical interconversion of (*)OOQOOH ((*)OOQOOH-> HOOQOO(*)), H
      migration reactions (from carbon to oxygen), HO2 elimination, and cyclic ether
      formation with elimination of OH radical. We evaluate the significance of
      reaction pathways by comparing rate coefficients in the high-pressure limit.
      Unexpectedly, we find a low activation barriers for 1,8 H-migration of
      RC(?O)OCH2OO(*). We also find peroxy radical interconversion of (*)OOQOOH
      radicals from methyl butanoate commonly possess the lowest barriers of any
      unimolecular reaction of these radicals, despite that they proceed via 8-, 10-
      and 11-member ring transition states. At temperatures relevant to autoignition,
      these peroxy radical interconversions are dominant or significant reaction
      pathways. This means that some (*)OOQOOH radicals that were expected to be
      produced in negligible yields are, instead, major products in the autoignition of
      methylbutanoate (MB). These reactions have not previously been considered for MB,
      and will require revision of models of autoignition of methyl butanoate and other
      esters. 

PMID- 25760924
TI  - STAT3 controls IL6-dependent regulation of serotonin transporter function and
      depression-like behavior.
AB  - Experimental evidence suggests a role for the immune system in the
      pathophysiology of depression. A specific involvement of the proinflammatory
      cytokine interleukin 6 (IL6) in both, patients suffering from the disease and
      pertinent animal models, has been proposed. However, it is not clear how IL6
      impinges on neurotransmission and thus contributes to depression. Here we tested
      the hypothesis that IL6-induced modulation of serotonergic neurotransmission
      through the STAT3 signaling pathway contributes to the role of IL6 in depression.
      Addition of IL6 to JAR cells, endogenously expressing SERT, reduced SERT activity
      and downregulated SERT mRNA and protein levels. Similarly, SERT expression was
      reduced upon IL6 treatment in the mouse hippocampus. Conversely, hippocampal
      tissue of IL6-KO mice contained elevated levels of SERT and IL6-KO mice displayed
      a reduction in depression-like behavior and blunted response to acute
      antidepressant treatment. STAT3 IL6-dependently associated with the SERT promoter
      and inhibition of STAT3 blocked the effect of IL6 in-vitro and modulated
      depression-like behavior in-vivo. These observations demonstrate that IL6
      directly controls SERT levels and consequently serotonin reuptake and identify
      STAT3-dependent regulation of SERT as conceivable neurobiological substrate for
      the involvement of IL6 in depression. 

PMID- 25760926
TI  - miR-218 inhibits the invasion and migration of colon cancer cells by targeting
      the PI3K/Akt/mTOR signaling pathway.
AB  - Colon cancer is one of the most common and lethal malignancies worldwide. Despite
      major advances in the treatment of colon cancer, the prognosis remains very poor.
      Thus, novel and effective therapies for colon cancer are urgently needed. In the
      present study, the expression status of miR-218 and the role of the
      phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt)/mammalian target of
      rapamycin (mTOR) pathway were investigated in colon cancer samples. Firstly, we
      observed that miR-218 expression was significantly reduced, while PI3K/Akt/mTOR
      pathway activity was enhanced. The overexpression of miR-218 suppressed the
      proliferation, migration and invasion of LoVo colon cancer cells, whereas the
      inhibition of miR-218 promoted these processes. Furthermore, the PI3K/Akt/mTOR
      signaling pathway was identified as a direct target of miR-218. The upregulation
      of miR-218 inhibited the activation of the PI3K/Akt/mTOR signaling pathway, as
      well as the expression of matrix metalloproteinase (MMP)9. The downregulation of
      miR-218 activated the PI3K/Akt/mTOR signaling pathway and promoted MMP9
      expression. Taken together, our results demonstrate that miR-218 suppresses the
      proliferation, migration and invasion of LoVo colon cancer cells by targeting the
      PI3K/Akt/mTOR signaling pathway and MMP9. Our data indicate that miR-218 is a
      potential target in the treatment of colon cancer.

PMID- 25760927
TI  - Persistence of levator ani sonographic defect detected by three-dimensional
      transperineal sonography in primiparous women.
AB  - OBJECTIVES: Correlation of the sonographic appearance of levator ani muscle (LAM)
      injury soon after delivery with that at long-term follow-up has not been
      described fully. We aimed to compare results of three-dimensional (3D)
      transperineal sonographic (TPS) evaluation of the LAM from the period immediately
      postpartum with long-term follow-up, to determine whether sonographic findings
      persist over time. METHODS: Primiparous women (n = 210) who had been examined by
      3D-TPS in a previous study to determine LAM trauma 24-72 hours after delivery
      were invited to participate in a follow-up examination 3-21 months postpartum. We
      included in this study only women who were not pregnant when approached and who
      had not given birth in the interim. LAM trauma was diagnosed with 3D-TPS when we
      observed discontinuity and distortion of the most anteromedial part of the
      pubovisceral muscle in the coronal C-plane or rendered image. Initial and follow
      up 3D-TPS results were compared using Cohen's kappa test for inter-rater
      agreement. RESULTS: Among the 87 women included in this study we found strong
      correlation between earlier and later sonographic appearance of LAM: 17/21 women
      with a sonographic finding of LAM injury in the period immediately postpartum
      were positive in the follow-up examination, and only 2/66 women negative for LAM
      damage at the first examination were found to have sonographic evidence of LAM
      defect at follow-up (Cohen's kappa, 0.805 (95% CI, 0.656-0.954), P < 0.001).
      CONCLUSIONS: Our findings suggest that 3D-TPS of the LAM is a reliable
      examination. A sonographic finding of LAM defect identified in the period
      immediately postpartum persists months or years after delivery; therefore, this
      test may be performed following delivery, or may be delayed without impacting the
      result. It is likely that this sonographic defect represents real anatomical
      disruption and is not an imaging artifact.

PMID- 25760928
TI  - CholMine: Determinants and Prediction of Cholesterol and Cholate Binding Across
      Nonhomologous Protein Structures.
AB  - Identifying physiological ligands is necessary for annotating new protein
      structures, yet this presents a significant challenge to biologists and
      pharmaceutical chemists. Here we develop a predictor of cholesterol and cholate
      binding that works across diverse protein families, extending beyond sequence
      motif-based prediction. This approach combines SimSite3D site comparison with the
      detection of conserved interactions in cholesterol/cholate bound crystal
      structures to define three-dimensional interaction motifs. The resulting
      predictor identifies cholesterol sites with an ~82% unbiased true positive rate
      in both membrane and soluble proteins, with a very low false positive rate
      relative to other predictors. The CholMine Web server can analyze users'
      structures, detect those likely to bind cholesterol/cholate, and predict the
      binding mode and key interactions. By deciphering the determinants of binding for
      these important steroids, CholMine may also aid in the design of selective
      inhibitors and detergents for targets such as G protein coupled receptors and
      bile acid receptors. 

PMID- 25760929
TI  - An Experimental Examination of the Interaction between Mood Induction Task and
      Personality Psychopathology on State Emotion Dysregulation.
AB  - While emotion dysregulation has been investigated as a key variable in the
      development and persistence of personality psychopathology, few studies have
      explored state emotion dysregulation among individuals with personality disorders
      (PDs). The current study addresses this void in the literature through a
      laboratory investigation of state emotion dysregulation among participants with
      and without PDs. To facilitate this goal, participants were matched to pairs
      based on similar personality features and were randomized to one of two
      behavioral analogues; either the Paced Auditory Serial Addition Task-Computerized
      (PASAT-C) or an interpersonally based mood induction. As hypothesized, PD
      participants in the PASAT-C reported significantly more difficulty with
      impulsivity and emotion regulation strategies. Contrary to expectations, the PD
      group in the interpersonal task demonstrated significantly less difficulty with
      non-acceptance of emotion and emotional clarity and significantly greater
      positive affect compared to non-PD participants. Implications for these findings
      and directions for future research are discussed. 

PMID- 25760930
TI  - Is black always the opposite of white? An investigation on the comprehension of
      antonyms in people with schizophrenia and in healthy participants.
AB  - The present investigation sought to expand our understanding of the cognitive
      processes underlying the recognition of antonyms and to evaluate whether these
      processes differed in patients with schizophrenia and in healthy controls.
      Antonymy is the most robust of the lexico-semantic relations and is relevant to
      both the mental organization of the lexicon and the organization of coherent
      discourse, as attested by the resurgence of interest in antonymy in the
      linguistic and psychological domains. In contrast, the vast literature on
      semantic processing in schizophrenia almost ignored antonymy. In this study, we
      tested the online comprehension of antonyms in 39 Italian patients with paranoid
      schizophrenia and in an equal number of pairwise-matched healthy controls.
      Participants read a definitional sentence fragment (e.g., the opposite of black
      is), followed by the correct antonym (white) or by a semantically unrelated word
      (nice), and judged whether or not the target word was correct. Patients were
      rather accurate in identifying antonyms, but compared to controls, they showed
      longer response times and higher priming scores, suggesting an exaggerated
      contextual facilitation. Presumably, this reflects a deficient controlled
      semantic processing and an overreliance on stored semantic representations. 

PMID- 25760931
TI  - Antibody engineering for increased potency, breadth and half-life.
AB  - PURPOSE OF REVIEW: This review highlights recent developments in HIV-1 antibody
      engineering and discusses the effects of increased polyreactivity on serum half
      lives of engineered antibodies. RECENT FINDINGS: Recent studies have uncovered a
      wealth of information about the relationship between the sequences and efficacies
      of anti-HIV-1 antibodies through a combination of bioinformatics, structural
      characterization and in vivo studies. This knowledge has stimulated efforts to
      enhance antibody breadth and potency for therapeutic use. Although some
      engineered antibodies have shown increased polyreactivity and short half-lives,
      promising efforts are circumventing these problems. SUMMARY: Antibodies are
      desirable as therapeutics due to their ability to recognize targets with both
      specificity and high affinity. Furthermore, the ability of antibodies to
      stimulate Fc-mediated effector functions can increase their utility. Thus, mAbs
      have become central to strategies for the treatment of various diseases. Using
      both targeted and library-based approaches, antibodies can be engineered to
      improve their therapeutic properties. This article will discuss recent antibody
      engineering efforts to improve the breadth and potency of anti-HIV-1 antibodies.
      The polyreactivity of engineered HIV-1 bNAbs and the effect on serum half-life
      will be explored along with strategies to overcome problems introduced by
      engineering antibodies. Finally, advances in creating bispecific anti-HIV-1
      reagents are discussed.

PMID- 25760932
TI  - HIV broadly neutralizing antibody targets.
AB  - PURPOSE OF REVIEW: To provide an update on neutralizing antibody targets in the
      context of the recent HIV-1 envelope trimer structure, describe new antibody
      isolation technologies, and discuss the implications of these data for HIV-1
      prevention and therapy. RECENT FINDINGS: Recent advances in B-cell technologies
      have dramatically expanded the number of antibodies isolated from HIV-infected
      donors with broadly neutralizing plasma activity. These, together with the first
      high-resolution crystal and cryo-electron microscopy (cryo-EM) structures of a
      cleaved, prefusion HIV-1 trimer, have defined new regions susceptible to
      neutralization. This year, three epitopes in the gp120-gp41 interface were
      structurally characterized, highlighting the importance of prefusion gp41 as a
      target. Similar to many other broadly neutralizing antibody epitopes, these new
      antibodies define a target that is also highly glycan dependent. Collectively,
      the epitopes for broadly neutralizing antibodies now reveal a continuum of
      vulnerability spanning the length of the HIV-1 envelope trimer. SUMMARY: Progress
      in the last year has provided support for the use of rationally stabilized whole
      HIV-1 trimers as immunogens for eliciting antibodies to multiple epitopes.
      Furthermore, the increasing number of broad and potent antibodies with the
      potential for synergistic/complementary combinations opens up new avenues for
      preventing and treating HIV-1 infection.

PMID- 25760933
TI  - History of passive antibody administration for prevention and treatment of
      infectious diseases.
AB  - PURPOSE OF REVIEW: We describe the history of passive immunization to provide
      context for the series of articles to follow. The history of passive immunization
      with antibodies to prevent or treat infectious diseases is a story of different
      eras. There was an extraordinary era of discovery and clinical implementation
      before the chemical nature of antibodies was even known. This empirical process
      provided the resources and reagents used to describe and characterize humoral
      immunity, better define the chemical properties and structure of antibodies, and
      extend the clinical use of immunoglobulin products to treat or prevent multiple
      viral and bacterial diseases over the ensuing several decades. The next distinct
      era came with the discovery of processes to produce monoclonal antibodies (mAbs),
      and development of more specific therapies. Interestingly, mAb technology
      resulted in many products to treat autoimmune and allergic diseases, but only one
      common infectious disease, respiratory syncytial virus, and only in a restricted
      population of high-risk infants. RECENT FINDINGS: The current era began in 2003
      with a series of publications demonstrating processes for rapidly producing human
      mAbs. SUMMARY: This technology combined with new sequencing technology, advances
      in structural biology, atomic-level molecular design, and increased capacity for
      synthetic biology, promises new opportunities to apply passive immunization to
      the prevention and treatment of infectious diseases.

PMID- 25760934
TI  - Protomers of benzocaine: solvent and permittivity dependence.
AB  - The immediate environment of a molecule can have a profound influence on its
      properties. Benzocaine, the ethyl ester of para-aminobenzoic acid that finds an
      application as a local anesthetic, is found to adopt in its protonated form at
      least two populations of distinct structures in the gas phase, and their relative
      intensities strongly depend on the properties of the solvent used in the
      electrospray ionization process. Here, we combine IR-vibrational spectroscopy
      with ion mobility-mass spectrometry to yield gas-phase IR spectra of
      simultaneously m/z and drift-time-resolved species of benzocaine. The results
      allow for an unambiguous identification of two protomeric species: the N- and O
      protonated forms. Density functional theory calculations link these structures to
      the most stable solution and gas-phase structures, respectively, with the
      electric properties of the surrounding medium being the main determinant for the
      preferred protonation site. The fact that the N-protonated form of benzocaine can
      be found in the gas phase is owed to kinetic trapping of the solution-phase
      structure during transfer into the experimental setup. These observations confirm
      earlier studies on similar molecules where N- and O-protonation have been
      suggested. 

PMID- 25760935
TI  - The role of vitamin D in the control of Leishmania infection.
AB  - Vitamin D has been described as an essential element for maintaining the
      homeostasis of mineral content in the body and bone architecture. However, our
      view of the physiological functions of this micronutrient has radically changed,
      owing to the vast number of properties, not calcium-related, mediated by its
      nuclear receptor. This receptor has been found in a variety of cells, including
      the immune cells, where many of the functions performed by vitamin D are related
      to inflammation. Although the effect of vitamin D has been widely studied in many
      diseases caused by viruses or bacteria, very little is known about its role in
      parasitic diseases, such as leishmaniasis, which is a vector-borne disease caused
      by different species of the intracellular parasite Leishmania spp. This disease
      occurs as a spectrum of different clinical syndromes, all of them characterized
      by a large amount of tissue damage, sometimes leading to necrosis. Owing to the
      involvement of vitamin D in inflammation and wound healing, its role in
      leishmaniasis must be relevant, and could be used as an adjuvant for the control
      of this parasitic disease, opening a possibility for a therapeutic application.

PMID- 25760936
TI  - Screening of variable importance for optimizing electrodialytic remediation of
      heavy metals from polluted harbour sediments.
AB  - Using multivariate design and modelling, the optimal conditions for
      electrodialytic remediation (EDR) of heavy metals were determined for polluted
      harbour sediments from Hammerfest harbour located in the geographic Arctic region
      of Norway. The comparative importance of the variables, current density,
      remediation time, light/no light, the liquid-solid ratio and stirring rate of the
      sediment suspension, was determined in 15 laboratory-scale EDR experiments by
      projection to latent structures (PLS). The relation between the X matrix
      (experimental variables) and the Y matrix (removal efficiencies) was computed and
      variable importance in the projection was used to assess the influence of the
      experimental variables. Current density and remediation time proved to have the
      highest influence on the remediation of the heavy metals Cr, Cu, Ni, Pb and Zn in
      the studied experimental domain. In addition, it was shown that excluding the
      acidification time improved the PLS model, indicating the importance of applying
      a limited experimental domain that covers the removal phases of each heavy metal
      in the specific sediment. Based on PLS modelling, the optimal conditions for
      remediating the Hammerfest sediment were determined; operating in the
      experimental domain of 0.5-0.8 mA/cm(2) and a remediation time after
      acidification of 450-570 h met acceptable levels according to Norwegian sediment
      quality guidelines.

PMID- 25760937
TI  - Proteomics analysis of Xenopus laevis gonad tissue following chronic exposure to
      atrazine.
AB  - Atrazine is the most commonly detected pesticide contaminant in ground and
      surface water. Previous studies have shown that atrazine is an endocrine
      disruptor owing to its adverse effects on the male reproductive system in several
      vertebrates, but very few molecular mechanisms for these effects have been
      revealed. In the present study, Xenopus laevis were exposed to 100 ppb of
      atrazine for 120 d, and then the isobaric tags for relative and absolute
      quantitation (iTRAQ) technique was used to detect global changes in protein
      profiles of the testes and ovaries. The results showed that 100 ppb of atrazine
      exposure adversely affected the growth of X. laevis and did not induce
      hermaphroditism but delayed or prevented the development of male seminiferous
      tubules. Proteomic analysis showed that atrazine altered expression of 143 and
      121 proteins in the testes and ovaries, respectively, and most of them are
      involved in cellular and metabolic processes and biological regulation based on
      their biological processes. In addition, apoptosis, tight junctions, and
      metabolic pathways were significantly altered in the atrazine-treated gonads.
      Based on the above results, it is postulated that the reproductive toxicity of
      atrazine may be the result of disruption of tight junctions and metabolic
      signaling pathways and/or induction of apoptosis in germ cells.

PMID- 25760939
TI  - Water-soluble Py-BIPS spiropyrans as photoswitches for biological applications.
AB  - The ultrafast photochemistry of a new spiropyran photoswitch (Py-BIPS) has been
      investigated, revealing many advantages in the application in water over the
      previously studied spiropyrans. Functionalized Py-BIPS derivatives are presented
      for the study of pH dependence, stability, toxicity, and the thermal and
      photochemical behavior on longer time scales in aqueous media using several
      spectroscopic methods. These investigations pave the way for the practical use of
      Py-BIPS derivatives as photoswitchable ligands of biomolecules. 

PMID- 25760940
TI  - Fluorescent sensing of monofunctional platinum species.
AB  - We report here FDCPt1, a novel selective fluorescent sensor for monofunctional
      platinum species. In the presence of such species, FDCPt1 exhibits a 70-fold
      increase in fluorescence emission, and can be used to monitor the metabolism of
      Pt(II)-based complexes in colorectal cancer cells. This probe is therefore
      expected to be valuable in studying changes in Pt coordination and distribution
      during chemotherapy.

PMID- 25760938
TI  - Roles of lipoxin A4 receptor activation and anti-interleukin-1beta antibody on
      the toll-like receptor 2/mycloid differentiation factor 88/nuclear factor-kappaB
      pathway in airway inflammation induced by ovalbumin.
AB  - Previous studies investigating the role of toll-like receptors (TLRs) in asthma
      have been inconclusive. It has remained elusive whether the toll-like receptors
      (TLR2)/mycloid differentiation factor 88 (MyD88)/nuclear factor (NF)-kappaB
      signaling pathway is involved in lipoxin A4 (LXA4)-induced protection against
      asthma. Therefore, the present study investigated whether ovalbumin (OVA)-induced
      airway inflammation is mediated by upregulation of the TLR2/MyD88/NF-kappaB
      signaling pathway, and whether it proceeds via the inhibition of the activation
      of the LXA4 receptor and anti-interleukin (IL)-1beta antibodies. Mice with airway
      inflammation induced by OVA administration were treated with or without a LXA4
      receptor agonist, BML-111 and anti-IL-1beta antibody. Serum levels of IL-1beta,
      IL-4, IL-8 and interferon-gamma (IFN-gamma) were assessed, and levels of IL
      1beta, IL-4, IL-8 and OVA-immunoglobulin (Ig)E, as well as leukocyte counts in
      the bronchoalveolar lavage fluid (BALF) were measured. Pathological features and
      expression of TLR2, MyD88 and NF-kappaB in the lungs were analyzed. Expression of
      TLR2 and MyD88, and activation of NF-kappaB in leukocytes as well as levels of IL
      4, IL-6 and IL-8 released from leukocytes exposed to IL-1beta were assessed. OVA
      treatment increased the levels of IL-1beta, IL-4 and IL-8 in the serum and BLAF,
      the number of leukocytes and the levels of OVA-IgE in the BALF, the expression of
      TLR2 and MyD88, and the activation of NF-kappaB in the lung. These increments
      induced by OVA were inhibited by treatment with BML-111 and anti-IL-1beta
      antibodies. Treatment of the leukocytes with BML-111 or TLR2 antibody, or MyD88
      or NF-kappaB inhibitor, all blocked the IL-1beta-triggered production of IL-4, IL
      6 and IL-8 and activation of NF-kappaB. Treatment of the leukocytes with BML-111
      or TLR2 antibody suppressed IL-1beta-induced TLR2 and MyD88 expression. The
      present study therefore suggested that OVA-induced airway inflammation is
      mediated by the TLR2/MyD88/NF-kappaB pathway. IL-1beta has a pivotal role in the
      airway inflammation and upregulation of the TLR2/MyD88/NF-kappaB pathway induced
      by OVA. BML-111 and anti-IL-1beta antibody restrains the OVA-induced airway
      inflammation via downregulation of the TLR2/MyD88/NF-kappaB pathway.

PMID- 25760941
TI  - The role of peroxyl radicals in polyester degradation--a mass spectrometric
      product and kinetic study using the distonic radical ion approach.
AB  - Mass spectrometric techniques were used to obtain detailed insight into the
      reactions of peroxyl radicals with model systems of (damaged) polyesters. Using a
      distonic radical ion approach, it was shown that N-methylpyridinium peroxyl
      radical cations, Pyr(+)OO, do not react with non-activated C-H bonds typically
      present in polyesters that resist degradation. Structural damage in the polymer,
      for example small amounts of alkene moieties formed during the manufacturing
      process, is required to enable reaction with Pyr(+)OO, which proceeds with high
      preference through addition to the pi system rather than via allylic hydrogen
      atom abstraction (kadd/kHAT > 20 for internal alkenes). This is due to the very
      fast and strongly exothermic subsequent fragmentation of the peroxyl-alkene
      radical adduct to epoxides and highly reactive Pyr(+)O, which both could promote
      further degradation of the polymer through non-radical and radical pathways. This
      work provides essential experimental support that the basic autoxidation
      mechanism is a too simplistic model to rationalize radical mediated degradation
      of polymers under ambient conditions. 

PMID- 25760942
TI  - Masked suffix priming and morpheme positional constraints.
AB  - Although masked stem priming (e.g., dealer-DEAL) is one of the most established
      effects in visual word identification, it is less clear whether primes and
      targets sharing a suffix (e.g., kindness-WILDNESS) also yield facilitation. In a
      new take on this issue, we show that prime nonwords facilitate lexical decisions
      to target words ending with the same suffix (sheeter-TEACHER) compared to a
      condition where the critical suffix was substituted by another one (sheetal
      TEACHER) or by an unrelated nonmorphological ending (sheetub- TEACHER). We also
      show that this effect is genuinely morphological, as no priming emerged in
      noncomplex items with the same orthographic characteristics (sportel-BROTHEL vs.
      sportic-BROTHEL vs. sportur-BROTHEL). In a further experiment, we took advantage
      of these results to assess whether suffixes are recognized in a position-specific
      fashion. Masked suffix priming did not emerge when the relative order of stems
      and suffixes was reversed in the prime nonwords-ersheet did not yield any time
      saving in the identification of teacher as compared to either alsheet or obsheet.
      We take these results to show that -er was not identified as a morpheme in
      ersheet, thus indicating that suffix identification is position specific. This
      conclusion is in line with data on interference effects in nonword rejection and
      strongly constrains theoretical proposals on how complex words are identified. In
      particular, because these findings were reported in a masked priming paradigm,
      they suggest that positional constraints operate early, most likely at a
      prelexical level of morpho-orthographic analysis. 

PMID- 25760943
TI  - Alcoholic fermentation of Saccharomyces cerevisiae, Pichia stipitis and Zymomonas
      mobilis in the presence of inhibitory compounds and seawater.
AB  - Production of cellulosic ethanol and holocellulosic ethanol from vegetable or
      microbial biomass starts with a hydrolysate containing compounds which may
      produce negative effects in the enzymatic hydrolysis and fermentation stages due
      to the need of pretreatment of the materials. In this way, the simultaneous
      presence of hydroxymethylfurfural (HMF), furfural, acetic acid, levulinic acid,
      and formic acid in different concentrations was tested in the fermentation using
      Saccharomyces cerevisiae, Pichia stipitis, and Zymomonas mobilis. The
      substitution of freshwater by seawater in the culture medium was also analyzed.
      Thus, inhibitory effects were stronger in the fermentation using P. stipitis,
      followed by Z. mobilis and S. cerevisiae. Formic acid and acetic acid presented
      more significant effects among the inhibitory compounds, followed by HMF,
      furfural and levulinic acid. Fermentation performed in culture medium with
      seawater showed promising results, especially in the ethanol yield using S.
      cerevisiae (0.50 g ethanol/g glucose) and Z. mobilis (0.49 g ethanol/g glucose).
      Whereas the production of cellulosic ethanol and holocellulosic ethanol are in
      early stages of development on an industrial scale, and that the availability and
      use of freshwater may cause socio-environmental problems for expansion of ethanol
      production, the use of seawater appears as an alternative to mitigate this
      problem.

PMID- 25760944
TI  - Molecular characterization of Echinococcus granulosus sensu lato from farm
      animals in Egypt.
AB  - Little is known on the diversity and public health significance of Echinococcus
      species in livestock in Egypt. In this study, 37 individual hydatid cysts were
      collected from dromedary camels (n=28), sheep (n=7) and buffalos (n=2). DNA was
      extracted from protoscoleces/germinal layer of individual cysts and amplified by
      PCR targeting nuclear (actin II) and mitochondrial (COX1 and NAD1) genes. Direct
      sequencing of amplicons indicated the presence of Echinococcus canadenesis (G6
      genotype) in 26 of 28 camel cysts, 3 of 7 sheep cysts and the 2 buffalo derived
      cysts. In contrast, Echinococcus granulosus sensu stricto (G1 genotype) was
      detected in one cyst from a camel and 4 of 7 cysts from sheep, whereas
      Echinococcus ortleppi (G5 genotype) was detected in one cyst from a camel. This
      is the first identification of E. ortleppi in Egypt. 

PMID- 25760945
TI  - Regulation of neuronal cav3.1 channels by cyclin-dependent kinase 5 (Cdk5).
AB  - Low voltage-activated (LVA) T-type Ca2+ channels activate in response to
      subthreshold membrane depolarizations and therefore represent an important source
      of Ca2+ influx near the resting membrane potential. In neurons, these proteins
      significantly contribute to control relevant physiological processes including
      neuronal excitability, pacemaking and post-inhibitory rebound burst firing. Three
      subtypes of T-type channels (Cav3.1 to Cav3.3) have been identified, and using
      functional expression of recombinant channels diverse studies have validated the
      notion that T-type Ca2+ channels can be modulated by various endogenous ligands
      as well as by second messenger pathways. In this context, the present study
      reveals a previously unrecognized role for cyclin-dependent kinase 5 (Cdk5) in
      the regulation of native T-type channels in N1E-115 neuroblastoma cells, as well
      as recombinant Cav3.1channels heterologously expressed in HEK-293 cells. Cdk5 and
      its co-activators play critical roles in the regulation of neuronal
      differentiation, cortical lamination, neuronal cell migration and axon outgrowth.
      Our results show that overexpression of Cdk5 causes a significant increase in
      whole cell patch clamp currents through T-type channels in N1E-115 cells, while
      siRNA knockdown of Cdk5 greatly reduced these currents. Consistent with this,
      overexpression of Cdk5 in HEK-293 cells stably expressing Cav3.1channels
      upregulates macroscopic currents. Furthermore, using site-directed mutagenesis we
      identified a major phosphorylation site at serine 2234 within the C-terminal
      region of the Cav3.1subunit. These results highlight a novel role for Cdk5 in the
      regulation of T-type Ca2+ channels. 

PMID- 25760946
TI  - T396I mutation of mouse Sufu reduces the stability and activity of Gli3
      repressor.
AB  - Hedgehog signaling is primarily transduced by two transcription factors: Gli2,
      which mainly acts as a full-length activator, and Gli3, which tends to be
      proteolytically processed from a full-length form (Gli3FL) to an N-terminal
      repressor (Gli3REP). Recent studies using a Sufu knockout mouse have indicated
      that Sufu is involved in regulating Gli2 and Gli3 activator and repressor
      activity at multiple steps of the signaling cascade; however, the mechanism of
      specific Gli2 and Gli3 regulation remains to be elucidated. In this study, we
      established an allelic series of ENU-induced mouse strains. Analysis of one of
      the missense alleles, SufuT396I, showed that Thr396 residue of Sufu played a key
      role in regulation of Gli3 activity. SufuT396I/T396I embryos exhibited severe
      polydactyly, which is indicative of compromised Gli3 activity. Concomitantly,
      significant quantitative reductions of unprocessed Gli3 (Gli3FL) and processed
      Gli3 (Gli3REP) were observed in vivo as well as in vitro. Genetic experiments
      showed that patterning defects in the limb buds of SufuT396I/T396I were rescued
      by a constitutive Gli3REP allele (Gli3?699), strongly suggesting that SufuT396I
      reduced the truncated Gli3 repressor. In contrast, SufuT396I qualitatively
      exhibited no mutational effects on Gli2 regulation. Taken together, the results
      of this study show that the Thr396 residue of Sufu is specifically required for
      regulation of Gli3 but not Gli2. This implies a novel Sufu-mediated mechanism in
      which Gli2 activator and Gli3 repressor are differentially regulated. 

PMID- 25760947
TI  - A novel therapy for melanoma developed in mice: transformation of melanoma into
      dendritic cells with Listeria monocytogenes.
AB  - Listeria monocytogenes is a gram-positive bacteria and human pathogen widely used
      in cancer immunotherapy because of its capacity to induce a specific cytotoxic T
      cell response in tumours. This bacterial pathogen strongly induces innate and
      specific immunity with the potential to overcome tumour induced tolerance and
      weak immunogenicity. Here, we propose a Listeria based vaccination for melanoma
      based in its tropism for these tumour cells and its ability to transform in vitro
      and in vivo melanoma cells into matured and activated dendritic cells with
      competent microbicidal and antigen processing abilities. This Listeria based
      vaccination using low doses of the pathogen caused melanoma regression by
      apoptosis as well as bacterial clearance. Vaccination efficacy is LLO dependent
      and implies the reduction of LLO-specific CD4+ T cell responses, strong
      stimulation of innate pro-inflammatory immune cells and a prevalence of LLO
      specific CD8+ T cells involved in tumour regression and Listeria elimination.
      These results support the use of low doses of pathogenic Listeria as safe
      melanoma therapeutic vaccines that do not require antibiotics for bacterial
      removal. 

PMID- 25760948
TI  - Wild gazelles of the southern Levant: genetic profiling defines new conservation
      priorities.
AB  - The mountain gazelle (Gazella gazelle), Dorcas gazelle (Gazella Dorcas) and
      acacia gazelle (Gazella arabica acacia) were historically abundant in the
      southern Levant, and more specifically in Israel. Anthropogenic and natural
      changes have caused a rapid decline in gazelle populations, raising concerns
      about their conservation status and future survival. The genetic profile of 111
      wild gazelles from Israel was determined based on three regions of mitochondrial
      DNA (control region, Cytochrome b and 12S ribosomal RNA) and nine nuclear
      microsatellite markers. Genetic analysis of the mountain gazelle population, the
      largest known population of this rare species, revealed adequate diversity levels
      and gene flow between subpopulations. Nevertheless, ongoing habitat degradation
      and other human effects, such as poaching, suggest the need for drastic measures
      to prevent species extinction. Dorcas gazelles in Israel displayed inbreeding
      within subpopulations while still maintaining considerable genetic diversity
      overall. This stable population, represented by a distinctive genetic profile, is
      fragmented and isolated from its relatives in neighboring localities. Based on
      the genetic profile of a newly sampled subpopulation in Israel, we provide an
      alternative hypothesis for the historic dispersal of Dorcas gazelle, from the
      Southern Levant to northern Africa. The small acacia gazelle population was
      closest to gazelles from the Farasan Islands of Saudi Arabia, based on
      mitochondrial markers. The two populations did not share haplotypes, suggesting
      that these two populations may be the last remnant wild gazelles of this species
      worldwide. Only a dozen acacia gazelles survive in Israel, and urgent steps are
      needed to ensure the survival of this genetically distinctive lineage. The
      genetic assessments of our study recognize new conservation priorities for each
      gazelle species in the Southern Levant. 

PMID- 25760951
TI  - New Generation of Orally Disintegrating Tablets for Sustained Drug Release: A
      Propitious Outlook.
AB  - Orally disintegrating tablets (ODTs) or orodispersible tablets are solid dosage
      forms that disintegrate within 3 minutes in the mouth into a paste that can be
      easily swallowed. ODTs have improved over the past years, in an attempt to
      produce a safe and efficient substitute to the conventional oral dosage forms,
      particularly for dysphagia patients. Since its introduction in the market in the
      1980s, ODTs expanded rapidly and achieved revenues over $3 billion in 2006 and
      sustaining 20% annual growth. It is therefore evident that ODTs carry good
      commercial value, however there is potential for improvement. Current sustained
      release technologies may be exploited and incorporated into an ODT to provide
      greater therapeutic value by reducing the need for multiple daily dosing regimens
      and improving patient adherence. A number of technologies such as polymer coated
      nanoparticles, stimuli-responsive polymers and ion-exchange resins have emerged
      to produce robust, sustained release orally disintegrating tablets (SR-ODT). The
      purpose of this review is to highlight these various approaches and techniques
      and how they have been utilised in an ODT formulation to extend differentiated
      line, market exclusivity and patent life. The review also explores future
      perspective and the potential challenges that SR-ODTs will face. 

PMID- 25760949
TI  - The interaction between circulating complement proteins and cutaneous
      microvascular endothelial cells in the development of childhood Henoch-Schonlein
      Purpura.
AB  - OBJECTIVE: In addition to IgA, the deposition of complement (C)3 in dermal
      vessels is commonly found in Henoch-Schonlein purpura (HSP). The aim of this
      study is to elucidate the role of circulating complement proteins in the
      pathogenesis of childhood HSP. METHODS: Plasma levels of C3a, C4a, C5a, and Bb in
      30 HSP patients and 30 healthy controls were detected by enzyme-linked
      immunosorbent assay (ELISA). The expression of C3a receptor (C3aR), C5a receptor
      (CD88), E-selectin, intercellular adhesion molecule 1 (ICAM-1), C3, C5,
      interleukin (IL)-8, monocyte chemotactic protein (MCP)-1, and RANTES by human
      dermal microvascular endothelial cells (HMVEC-d) was evaluated either by flow
      cytometry or by ELISA. RESULTS: At the acute stage, HSP patients had higher
      plasma levels of C3a (359.5 +/- 115.3 vs. 183.3 +/- 94.1 ng/ml, p < 0.0001), C5a
      (181.4 +/- 86.1 vs. 33.7 +/- 26.3 ng/ml, p < 0.0001), and Bb (3.7 +/- 2.6 vs. 1.0
      +/- 0.6 MUg/ml, p < 0.0001), but not C4a than healthy controls. Although HSP
      patient-derived acute phase plasma did not alter the presentation of C3aR and
      CD88 on HMVEC-d, it enhanced the production of endothelial C3 and C5. Moreover,
      C5a was shown in vitro to up-regulate the expression of IL-8, MCP-1, E-selectin,
      and ICAM-1 by HMVEC-d with a dose-dependent manner. CONCLUSION: In HSP, the
      activation of the complement system in part through the alternative pathway may
      have resulted in increased plasma levels of C3a and C5a, which, especially C5a,
      may play a role in the disease pathogenesis by activating endothelium of
      cutaneous small vessels.

PMID- 25760952
TI  - Evaluation of air photoactivation at linear accelerators for radiotherapy.
AB  - High-energy x-rays produced by radiotherapy accelerators operating at potentials
      above 10 MV may activate the air via (gamma, n) reactions with both oxygen and
      nitrogen. While the activation products are relatively short-lived, personnel
      entering the accelerator room may inhale some radioactive air, which warrants
      internal dosimetry assessments. This work illustrates a method based on the use
      of ammonium nitrate solutions for the evaluation of photon-induced air activation
      and for the estimate of internal doses to radiotherapy personnel. Air activation
      and internal dosimetry assessments based on our method are presented for some
      widespread radiotherapy linear accelerator models. Our results indicate that the
      equivalent dose to the lungs of radiotherapy personnel is negligible for beam
      energies below 18 MeV.

PMID- 25760953
TI  - Regulation of the C/EBPalpha signaling pathway in acute myeloid leukemia
      (Review).
AB  - The transcription factor CCAAT/enhancer binding protein alpha (C/EBPalpha), as a
      critical regulator of myeloid development, directs granulocyte and monocyte
      differentiation. Various mechanisms have been identified to explain how
      C/EBPalpha functions in patients with acute myeloid leukemia (AML). C/EBPalpha
      expression is suppressed as a result of common leukemia-associated genetic and
      epigenetic alterations such as AML1-ETO, RARalpha-PLZF or gene promoter
      methylation. Recent data have shown that ubiquitination modification also
      contributes to its downregulation. In addition, 10-15% of patients with AML in an
      intermediate cytogenetic risk subgroup were characterized by mutations of the
      C/EBPalpha gene. As a transcription factor, C/EBPalpha can translocate into the
      nucleus and further regulate a variety of genes directly or indirectly, which are
      all key factors for cell differentiation. This review summarizes recent reports
      concerning the dysregulation of C/EBPalpha expression at various levels in human
      AML. The currently available data are persuasive evidence suggesting that
      impaired abnormal C/EBPalpha expression contributes to the development of AML,
      and restoration of C/EBPalpha expression as well as its function represents a
      promising target for novel therapeutic strategies in AML. 

PMID- 25760954
TI  - Lipid-lowering efficacy of atorvastatin.
AB  - BACKGROUND: This represents the first update of this review, which was published
      in 2012. Atorvastatin is one of the most widely prescribed drugs and the most
      widely prescribed statin in the world. It is therefore important to know the dose
      related magnitude of effect of atorvastatin on blood lipids. OBJECTIVES: Primary
      objective To quantify the effects of various doses of atorvastatin on serum total
      cholesterol, low-density lipoprotein (LDL)-cholesterol, high-density lipoprotein
      (HDL)-cholesterol and triglycerides in individuals with and without evidence of
      cardiovascular disease. The primary focus of this review was determination of the
      mean per cent change from baseline of LDL-cholesterol. Secondary objectives * To
      quantify the variability of effects of various doses of atorvastatin.* To
      quantify withdrawals due to adverse effects (WDAEs) in placebo-controlled
      randomised controlled trials (RCTs). SEARCH METHODS: We searched the Cochrane
      Central Register of Controlled Trials (CENTRAL) (Issue 11, 2013), MEDLINE (1966
      to December Week 2 2013), EMBASE (1980 to December Week 2 2013), Web of Science
      (1899 to December Week 2 2013) and BIOSIS Previews (1969 to December Week 2
      2013). We applied no language restrictions. SELECTION CRITERIA: Randomised
      controlled and uncontrolled before-and-after trials evaluating the dose response
      of different fixed doses of atorvastatin on blood lipids over a duration of three
      to 12 weeks. DATA COLLECTION AND ANALYSIS: Two review authors independently
      assessed eligibility criteria for studies to be included and extracted data. We
      collected information on withdrawals due to adverse effects from placebo
      controlled trials. MAIN RESULTS: In this update, we found an additional 42 trials
      and added them to the original 254 studies. The update consists of 296 trials
      that evaluated dose-related efficacy of atorvastatin in 38,817 participants.
      Included are 242 before-and-after trials and 54 placebo-controlled RCTs. Log dose
      response data from both trial designs revealed linear dose-related effects on
      blood total cholesterol, LDL-cholesterol, HDL-cholesterol and triglycerides. The
      Summary of findings table 1 documents the effect of atorvastatin on LDL
      cholesterol over the dose range of 10 to 80 mg/d, which is the range for which
      this systematic review acquired the greatest quantity of data. Over this range,
      blood LDL-cholesterol is decreased by 37.1% to 51.7% (Summary of findings table
      1). The slope of dose-related effects on cholesterol and LDL-cholesterol was
      similar for atorvastatin and rosuvastatin, but rosuvastatin is about three-fold
      more potent. Subgroup analyses suggested that the atorvastatin effect was greater
      in females than in males and was greater in non-familial than in familial
      hypercholesterolaemia. Risk of bias for the outcome of withdrawals due to adverse
      effects (WDAEs) was high, but the mostly unclear risk of bias was judged unlikely
      to affect lipid measurements. Withdrawals due to adverse effects were not
      statistically significantly different between atorvastatin and placebo groups in
      these short-term trials (risk ratio 0.98, 95% confidence interval 0.68 to 1.40).
      AUTHORS' CONCLUSIONS: This update resulted in no change to the main conclusions
      of the review but significantly increases the strength of the evidence. Studies
      show that atorvastatin decreases blood total cholesterol and LDL-cholesterol in a
      linear dose-related manner over the commonly prescribed dose range. New findings
      include that atorvastatin is more than three-fold less potent than rosuvastatin,
      and that the cholesterol-lowering effects of atorvastatin are greater in females
      than in males and greater in non-familial than in familial hypercholesterolaemia.
      This review update does not provide a good estimate of the incidence of harms
      associated with atorvastatin because included trials were of short duration and
      adverse effects were not reported in 37% of placebo-controlled trials.

PMID- 25760955
TI  - Varying goals and approaches of innovation centers in academic health systems: a
      semistructured qualitative study.
AB  - PURPOSE: The medical community has seen a high level of interest in innovation
      over recent years. In response, health systems and medical centers have
      established innovation offices or centers, but their processes and practices for
      fostering innovation are not well understood. This information could help leaders
      in the medical community discern and develop criteria for assessing the tools and
      approaches most effective in fostering innovation. METHOD: The authors outlined a
      framework for examining factors involved when health systems attempt to foster
      innovation, and used the framework to design a semistructured qualitative
      interview study to collect information in 2012 and 2013 about how a purposive
      sample of three health systems have implemented strategies for fostering and
      supporting innovation. RESULTS: All interview sites carried out some form of in
      house innovation strategy, and experienced institution-level barriers to
      innovation. A common barrier was having the right resources and infrastructure to
      support the transition from prototype and pilot to operations. All sites had
      funding support from senior leadership, but success metrics took different forms.
      CONCLUSIONS: This study demonstrated the usefulness of the framework for
      conceptualizing innovation in medicine and suggests the potential of collecting
      data to support the assessment of innovation programs. In the three centers
      studied, the authors found a range of strategies employed to foster innovation
      and a range of criteria used to assess success of the program. Further study
      should examine a larger sample of institutions and be carried out over a longer
      time frame to allow for assessment of success.

PMID- 25760956
TI  - The impact of intramural grants on educators' careers and on medical education
      innovation.
AB  - PURPOSE: The University of California, San Francisco (UCSF), Haile T. Debas
      Academy of Medical Educators Innovations Funding program awards competitive
      grants to create novel curricula and faculty development programs, compare
      pedagogical approaches, and design learner assessment methods. The authors
      examined the principal investigators' (PIs') perceptions of the impact of these
      intramural grants on their careers and on medical education innovation. METHOD:
      At 12 months (project completion) and 24 months (follow-up), PIs submit a
      progress report describing the impact of their grant on their careers, work with
      collaborators, subsequent funding, project dissemination, and the UCSF
      curriculum. The authors analyzed these reports using qualitative thematic
      analysis and achieved consensus in coding and interpretation through discussion.
      RESULTS: From 2001 to 2012, the program funded 77 PIs to lead 103 projects,
      awarding over $2.2 million. The authors analyzed reports from 88 grants (85.4%)
      awarded to 68 PIs (88.3%). PIs noted that the funding led to accelerated
      promotion, expanded networking opportunities, enhanced knowledge and skills, more
      scholarly publications and presentations, extramural funding, and local and
      national recognition. They also reported that the funding improved their status
      in their departments, enhanced their careers as medical educators, laid the
      foundation for subsequent projects, and engaged an array of stakeholders,
      including trainees and junior faculty. CONCLUSIONS: These modest intramural
      education grants not only created innovative, enduring programs but also promoted
      educators' professional identity formation, fostered collaborations, supported
      junior faculty in finding their desired career paths, provided advancement
      opportunities, and raised the local and national profiles of recipients.

PMID- 25760957
TI  - The Projected Responses of Residency-Sponsoring Institutions to a Reduction in
      Medicare Support for Graduate Medical Education: A National Survey.
AB  - PURPOSE: To assess the projected responses of residency-sponsoring institutions
      to the proposed reduction in Medicare's indirect medical education (IME)
      payments. METHOD: In 2012, the authors surveyed directors of graduate medical
      education (GME) programs, examining (1) overall responses to a reduction in IME
      reimbursement and (2) the value of individual residencies to the institution from
      the economic/operational and educational/public service points of view, to
      determine which programs may be at risk for downsizing. RESULTS: Responses from
      192 of 555 institutions (35% response rate) varied by the size of the
      institution's GME program. Of large programs (six or more residencies), 33 (33%)
      would downsize at a 10% reduction in IME reimbursement, focusing cuts on specific
      programs. Small programs (five or fewer residencies) were more likely to retain
      their existing residencies with modest IME payment reductions and to make across
      the-board cuts. The economic/operational value of specialties varied widely, with
      hospital-intensive residencies valued highest. Family medicine was valued highly
      from an economic/operational point of view only by small programs.
      Educational/public service value scores varied less and were higher for all
      specialties. Preventive medicine was not highly valued in either category.
      CONCLUSIONS: Even a modest decrease in IME reimbursement could trigger
      institutions to downsize their GME programs. Programs at the greatest risk for
      cuts may be those with modest economic/operational value but high societal value,
      like family medicine. The retention or expansion of training in family medicine
      may be most easily accomplished then at smaller institutions.

PMID- 25760958
TI  - Introduction of lewis acidic and redox-active sites into a porous framework for
      ammonia capture with visual color response.
AB  - Based on the Lewis acidic site and redox ability of bipyridinium ligand, a porous
      framework with an adsorption advantage for ammonia over water and color response
      ability has been constructed. The compound is highly stable and flexible to
      external stimuli, exhibiting reversible single-crystal-to-single-crystal
      transformations, in response to temperature change and NH3 capture. More
      attractively, the title compound shows obvious color change from yellow to dark
      blue when exposed to ammonia vapor within just a few seconds, indicating a strong
      ability to function as a visual colorimetric absorbent for ammonia. 

PMID- 25760959
TI  - Ball milling synthesized MnOx as highly active catalyst for gaseous POPs removal:
      significance of mechanochemically induced oxygen vacancies.
AB  - A rapid (1.5 h) one-step ball milling (BM) method was developed not only to
      modify commercial MnO2 via top-down approaches (BM0), but also to bottom-up
      synthesize MnO(x) by cogrinding of KMnO4 and MnC4H6O4 (BM1) or KMnO4 and MnSO4
      (BM2). Catalysts activity on gaseous POPs removal was tested using
      hexachlorobenzene (HCBz) as surrogate. Catalytic performance decreases in the
      order of BM2 ~ BM1 (T90% = 180-200  degrees C) > BM0 (260  degrees C) > CMO ~
      cryptomelane MnO2 (>300  degrees C). Both adsorption and destruction contribute
      to HCBz removal at 180  degrees C while destruction prevails at 200-300  degrees
      C. Mechanism studies show that destruction activity is lineally correlated with
      the amount of surface reactive oxygen species (Oads); stability is determined by
      the removal of surface chloride, which is associated with the mobility of bulk
      lattice oxygen (Olat); adsorption capacities are linearly correlated with surface
      area and pore structure. With the aid of extensive characterizations the
      excellent performance of BM prepared samples can be explained as (1) abundant
      surface vacancies enhance the generation of Oads; (2) massive bulk vacancies
      promote the mobility of bulk Olat; (3) large surface area and uniform pore size
      distribution facilitate the physisorption of HCBz.

PMID- 25760960
TI  - Fabrication of a high-performance dye-sensitized solar cell with 12.8% conversion
      efficiency using organic silyl-anchor dyes.
AB  - The co-sensitization of organic silyl-anchor dyes in dye-sensitized solar cells
      (DSSCs) using carbazole and coumarin dyes with organosilicon tethers for binding
      to titanium dioxide has been examined. We have succeeded in fabricating a high
      performance DSSC with a light-to-electric energy conversion efficiency of 12.8%
      under one sun simulated solar irradiation. 

PMID- 25760961
TI  - Non-small-cell lung cancer and miRNAs: novel biomarkers and promising tools for
      treatment.
AB  - Lung cancer is the leading cause of cancer-related death worldwide, with
      approximately 80-85% of cases being non-small-cell lung cancer (NSCLC). The
      miRNAs are small non-coding RNAs that regulate gene expression at a post
      transcriptional level by either degradation or inhibition of the translation of
      target genes. Evidence is mounting that miRNAs exert pivotal effects in the
      development and progression of human malignancies, including NSCLC. A better
      understanding of the role that miRNAs play in the disease will contribute to the
      development of new diagnostic biomarkers and individualized therapeutic tools. In
      the present review, we briefly describe the role of miRNAs in NSCLC as well as
      the possible future of these discoveries in clinical applications. 

PMID- 25760962
TI  - Phagocyte NADPH oxidase and specific immunity.
AB  - The phagocyte NADPH oxidase NOX2 produces reactive oxygen species (ROS) and is a
      well-known player in host defence. However, there is also increasing evidence for
      a regulatory role of NOX2 in adaptive immunity. Deficiency in phagocyte NADPH
      oxidase causes chronic granulomatous disease (CGD) in humans, a condition that
      can also be studied in CGD mice. Clinical observations in CGD patients suggest a
      higher susceptibility to autoimmune diseases, in particular lupus, idiopathic
      thrombocytopenic purpura and rheumatoid arthritis. In mice, a strong correlation
      exists between a polymorphism in a NOX2 subunit and the development of autoimmune
      arthritis. NOX2 deficiency in mice also favours lupus development. Both CGD
      patients and CGD mice exhibit increased levels of immunoglobulins, including
      autoantibodies. Despite these phenotypes suggesting a role for NOX2 in specific
      immunity, mechanistic explanations for the typical increase of CGD in autoimmune
      disease and antibody levels are still preliminary. NOX2-dependent ROS generation
      is well documented for dendritic cells and B-lymphocytes. It is unclear whether T
      lymphocytes produce ROS themselves or whether they are exposed to ROS derived
      from dendritic cells during the process of antigen presentation. ROS are
      signalling molecules in virtually any cell type, including T- and B-lymphocytes.
      However, knowledge about the impact of ROS-dependent signalling on T- and B
      lymphocyte phenotype and response is still limited. ROS might contribute to
      Th1/Th2/Th17 cell fate decisions during T-lymphocyte activation and might enhance
      immunoglobulin production by B-lymphocytes. In dendritic cells, NOX2-derived ROS
      might be important for antigen processing and cell activation. 

PMID- 25760963
TI  - NUCKS: a potential biomarker in cancer and metabolic disease.
AB  - Nuclear, casein kinase and cyclin-dependent kinase substrate (NUCKS), a protein
      similar to the HMG (high-mobility group) protein family, is one of the most
      modified proteins in the mammalian proteome. Although very little is known about
      the biological roles of NUCKS, emerging clinical evidence suggests that this
      protein can be a biomarker and therapeutic target in various human ailments,
      including several types of cancer. An inverse correlation between NUCKS protein
      levels and body mass index in humans has also been observed. Depletion of NUCKS
      in mice has been reported to lead to obesity and impaired glucose homoeostasis.
      Genome-wide genomic and proteomic approaches have revealed that NUCKS is a
      chromatin regulator that affects transcription. The time is now ripe for further
      understanding of the role of this novel biomarker of cancer and the metabolic
      syndrome, and how its sundry modifications can affect its function. Such studies
      could reveal how NUCKS could be a link between physiological cues and human
      ailments. 

PMID- 25760965
TI  - The Effects of a Multimodal Rehabilitation Program on Symptoms and Ground
      Reaction Forces in Runners With Patellofemoral Pain Syndrome.
AB  - CONTEXT: Patellofemoral pain (PFP) is one of the most frequent running-related
      injuries. However, few interventions taking into consideration the specificity of
      running have been shown to be effective in runners with PFP. OBJECTIVE: To
      evaluate the effects of a multimodal rehabilitation program including lower-limb
      strengthening/ motor-control exercises, advice on running biomechanics, and
      symptoms management on symptoms, strength, and ground-reaction forces in runners
      with PFP. DESIGN: Pre- to post- quasi-experimental. SETTING: Gait-analysis
      laboratory and private physical therapy clinic. PARTICIPANTS: 21 runners with PFP
      (34.1 +/- 6.0 y old, symptoms duration 38.1 +/- 45.5 mo). INTERVENTION: An 8-wk
      multimodal rehabilitation program including lower-limb- and core-strengthening
      and motor-control exercises, as well as advice on running gait and symptoms
      management. MAIN OUTCOME MEASURES: The Activities of Daily Living Scale of the
      Knee Outcome Survey (KOS-ADLS) questionnaire and visual analog scales for usual
      pain (VAS-U), worst pain (VAS-W), and pain during running (VAS-R) were used to
      assess changes in symptoms and function. Vertical ground-reaction forces (VGRF)
      during running and lower-limb isometric strength were also measured. RESULTS:
      Statistically and clinically significant improvements (P < .001) were reported on
      KOS-ADLS (+17.8 pts), VAS-U (-19.2 pts), VAS-W (-28.7 pts), and VAS-R (-32.2 pts)
      after the intervention. No significant changes in isometric strength were
      observed. The instantaneous vertical loading rate was decreased after the
      intervention (P = .002), and this reduction was correlated with changes in KOS
      ADLS scores (P = .028). CONCLUSION: This multimodal intervention was successful
      in reducing pain and improving function of runners with PFP. However, no
      significant changes in lower-limb strength were observed. It appears that changes
      in VGRF combined with appropriate training advice could explain the clinical
      outcomes.

PMID- 25760966
TI  - Evolutionary game theory in cancer: first steps in prediction of metastatic
      cancer progression?

PMID- 25760967
TI  - Tumor chemosensitization by physical exercise? Insights from an anidmal model.

PMID- 25760964
TI  - A novel miRNA-based predictive model for biochemical failure following post
      prostatectomy salvage radiation therapy.
AB  - PURPOSE: To develop a microRNA (miRNA)-based predictive model for prostate cancer
      patients of 1) time to biochemical recurrence after radical prostatectomy and 2)
      biochemical recurrence after salvage radiation therapy following documented
      biochemical disease progression post-radical prostatectomy. METHODS: Forty three
      patients who had undergone salvage radiation therapy following biochemical
      failure after radical prostatectomy with greater than 4 years of follow-up data
      were identified. Formalin-fixed, paraffin-embedded tissue blocks were collected
      for all patients and total RNA was isolated from 1mm cores enriched for tumor
      (>70%). Eight hundred miRNAs were analyzed simultaneously using the nCounter
      human miRNA v2 assay (NanoString Technologies; Seattle, WA). Univariate and
      multivariate Cox proportion hazards regression models as well as receiver
      operating characteristics were used to identify statistically significant miRNAs
      that were predictive of biochemical recurrence. RESULTS: Eighty eight miRNAs were
      identified to be significantly (p<0.05) associated with biochemical failure post
      prostatectomy by multivariate analysis and clustered into two groups that
      correlated with early (<= 36 months) versus late recurrence (>36 months). Nine
      miRNAs were identified to be significantly (p<0.05) associated by multivariate
      analysis with biochemical failure after salvage radiation therapy. A new
      predictive model for biochemical recurrence after salvage radiation therapy was
      developed; this model consisted of miR-4516 and miR-601 together with, Gleason
      score, and lymph node status. The area under the ROC curve (AUC) was improved to
      0.83 compared to that of 0.66 for Gleason score and lymph node status alone.
      CONCLUSION: miRNA signatures can distinguish patients who fail soon after radical
      prostatectomy versus late failures, giving insight into which patients may need
      adjuvant therapy. Notably, two novel miRNAs (miR-4516 and miR-601) were
      identified that significantly improve prediction of biochemical failure post
      salvage radiation therapy compared to clinico-histopathological factors,
      supporting the use of miRNAs within clinically used predictive models. Both
      findings warrant further validation studies.

PMID- 25760968
TI  - Head and neck squamous cell carcinoma and human papillomavirus: epidemiology,
      treatment and future trends.

PMID- 25760969
TI  - Report on the 14th Conference of the International Society of Geriatric Oncology.
AB  - 14th Conference of the International Society of Geriatric Oncology, Lisbon,
      Portugal, 23-25 October 2014 The annual international conference of the
      International Society of Geriatric Oncology gathered about 400 scientists in
      Lisbon in October 2014. Arti Hurria, President of the Society, opened the meeting
      and presented recent Globocan data on the development of the number of people
      newly diagnosed with cancer. From 2012 to the expected figures of 2035 the number
      of people aged 65 years and older diagnosed with cancer will increase by 108%.
      All areas of the world are concerned, not only the so called western Countries.
      Five major tracts covered important areas in the field of Geriatric Oncology:
      solid tumors; hematological malignancies; new therapies and basic science;
      nursing, supportive care and geriatric assessment; advocacy and social-economical
      issues. 

PMID- 25760970
TI  - Insights into E3805: the CHAARTED trial.

PMID- 25760971
TI  - Is there a role for nutritional supplements in cancer care? Challenges and
      solutions.
AB  - NS are commonly used by patients affected by cancer. Patients are using these
      supplements mainly to improve their quality of life in their cancer trajectory.
      An open and empathic approach to this use is essential for successful patient
      doctor communication. An informed approach that takes into consideration NS that
      are safe, with clues of possible effectiveness can lead to a better decision
      making and trust in this communication process.

PMID- 25760972
TI  - Role of obesity on the efficacy of exemestane plus ovarian suppression in hormone
      receptor-positive premenopausal breast cancer.

PMID- 25760974
TI  - Pertuzumab: a new anti-HER2 drug in the management of women with breast cancer.
AB  - Pertuzumab is a humanized monoclonal antibody targeting HER2 that is different
      from trastuzumab in that it binds to a different domain of HER2; hence, combining
      the two drugs leads to a more comprehensive blockade of the receptor. This is the
      first drug to receive fast-track approval from US FDA based on the pathologic
      complete response (as the primary end point) attained in patients treated with
      neoadjuvant chemotherapy for breast cancer. Pertuzumab is approved in first-line
      treatment in metastatic setting both by FDA and EMA in combination with
      trastuzumab and docetaxel. Combining two targeted therapies ('dual blockade')
      will certainly escalate treatment costs and it remains to be seen if this
      strategy will find its way in to the clinic for all patients.

PMID- 25760973
TI  - Development of bevacizumab in advanced cervical cancer: pharmacodynamic modeling,
      survival impact and toxicology.
AB  - Historically, patients with metastatic, persistent or recurrent cervical cancer
      had limited therapeutic options. Despite several Phase II/III clinical trials,
      the combination of cisplatin and paclitaxel remained the most effective
      chemotherapeutic regimen. In 2014, publication of Gynecologic Oncology Group 240
      represented the emergence of an alternate and effective therapeutic option. This
      prospective, randomized, Phase III clinical trial explored the impact of adding
      the antiangiogenic agent bevacizumab to two separate cytotoxic chemotherapy
      backbones. Importantly, the study met its primary end point, showing a survival
      advantage of approximately 4 months without detriment in quality of life. As
      such, a review of bevacizumab and its application in patients with advanced-stage
      cervical cancer is warranted.

PMID- 25760975
TI  - Sorafenib off-target effects predict outcomes in patients treated for
      hepatocellular carcinoma.
AB  - AIM: Sorafenib is the standard of care in advanced hepatocellular carcinoma. This
      study was aimed to identify clinical parameters that may predict survival in
      these patients. MATERIALS & METHODS: In this observational study, a training (226
      patients) and validation cohorts (54 patients) were analyzed for evaluating
      pretreatment and on-treatment parameters. RESULTS: At multivariate analysis, only
      on-treatment variables (skin toxicity, diarrhea and arterial hypertension -
      sorafenib off-target effects), alphafetoprotein and radiological responses
      predicted survival. Using the occurrence of off-target effects, a prognostic
      index able to distinguish three groups of patients with different survival was
      constructed and externally validated. CONCLUSION: In hepatocellular carcinoma
      patients, on-treatment variables are the best predictors of survival. Among
      these, sorafenib off-target effects may be the most useful indicators for
      prognostication in field practice.

PMID- 25760976
TI  - Assessment of early response to imatinib 800 mg after 400 mg progression by 18F
      fluorodeoxyglucose PET in patients with metastatic gastrointestinal stromal
      tumors.
AB  - INTRODUCTION: Imatinib is the standard first-line therapy for advanced
      gastrointestinal stromal tumor. (18)F-fluorodeoxyglucose PET computed tomography
      (FDG PET/CT) shows a faster response than computed tomography in nonpretreated
      patients. PATIENTS & METHODS: After disease progression on imatinib 400 mg, 16
      patients were exposed to 800 mg. Tumor response was evaluated by FDG PET/CT on
      days 7 and 37. Primary objective was to correlate early metabolic response (EMR)
      with progression-free survival (PFS). RESULTS: EMR by FDG PET/CT scan was not
      predictive of PFS. Median PFS in these patients was 3 months. Overall survival
      was influenced by gastric primary site (p = 0.05). CONCLUSION: The assessment of
      EMR by FDG PET/CT in patients with advanced gastrointestinal stromal tumor
      exposed to imatinib 800 mg was not predictive of PFS or overall survival.

PMID- 25760977
TI  - Intermittent docetaxel chemotherapy as first-line treatment for metastatic
      castration-resistant prostate cancer patients.
AB  - AIMS: The intermittent administration of chemotherapy is a means of preserving
      patients' quality of life (QL). The aim of this study was to verify whether the
      intermittent administration of docetaxel (DOC) improves the patients' QL.
      PATIENTS & METHODS: All patients received DOC 70 mg/m(2) every 3 weeks for eight
      cycles. The patients were randomized to receive DOC continuously or with a fixed
      3-month interval after the first four DOC courses. RESULTS: The study involved
      148 patients. There was no difference in QL between the groups receiving
      intermittent or continuous treatment. Intermittence had no detrimental effects on
      disease control. CONCLUSION: Although feasible and not detrimental, our results
      showed that true intermittent chemotherapy in metastatic castration-resistant
      prostate cancer patients failed to improve the patients' QL.

PMID- 25760978
TI  - Recurrence and metastasis of breast cancer is influenced by ovarian hormone's
      effect on breast cancer stem cells.
AB  - Cancer stem cells (CSCs) have recently attracted great interest because of their
      emerging role in initiation, progression and metastasis, combined with their
      intrinsic resistance to chemotherapy and radiation therapy. CSCs and its
      interaction with hormones in breast cancer are currently being investigated with
      the aim of uncovering the molecular mechanisms by which they evade conventional
      treatment regimens. In this review, we discuss recent experimental data and new
      perspectives in the area of steroid hormones and their cross-talk with breast
      CSCs. We have covered literature associated with biomarkers, hormone receptors
      and hormone responsive signaling pathways in breast CSC. In addition, we also
      discuss the role of miRNAs in hormone mediated regulation of breast CSCs.

PMID- 25760979
TI  - Beyond CTLA-4: novel immunotherapy strategies for metastatic melanoma.
AB  - The treatment of metastatic melanoma is rapidly evolving. The discovery of BRAF
      and MEK inhibitors was an important milestone. Unfortunately, although response
      rates are high, disease progression is universal. Despite the success of IL-2 and
      adjuvant IFL-alpha2b, these two agents remained the only approved immunotherapy
      approaches. In recent years, the use of immunotherapy has drawn attention with
      the recognition of the mechanisms of tumor immune evasion. Blockade of these
      mechanisms may improve outcomes. However, the potential adverse events, the
      optimal use of these modalities, the high cost and the absence of predictive
      markers remain unmet challenges. Herein, we review the immunotherapy strategies
      in melanoma, either approved or under evaluation, and present the relevant data
      concerning their efficacy and safety.

PMID- 25760980
TI  - Modern radiotherapeutic strategies in the management of lymphoma.
AB  - The history of radiation therapy in the treatment of malignancies is closely
      linked to its use in Hodgkin lymphoma. It was less than a decade after the first
      publication on x-rays that radiotherapy was used in the treatment of a Hodgkin
      lymphoma. Over time, radiotherapy has evolved with newer technology and better
      understanding of radiobiology. During this same time frame, the treatment of
      Hodgkin and non-Hodgkin lymphomas has also seen great progress. This review will
      provide detail on modern radiotherapy techniques, indications for utilization,
      and modern radiation field sizes and doses.

PMID- 25760981
TI  - Pulse radiolysis and ultra-high-performance liquid chromatography/high-resolution
      mass spectrometry studies on the reactions of the carbonate radical with vitamin
      B12 derivatives.
AB  - The reactions of the carbonate radical anion (CO3 (.) (-) ) with vitamin B12
      derivatives were studied by pulse radiolysis. The carbonate radical anion
      directly oxidizes the metal center of cob(II)alamin quantitively to give
      hydroxycobalamin, with a bimolecular rate constant of 2.0*10(9) M(-1) s(-1) . The
      reaction of CO3 (.) (-) with hydroxycobalamin proceeds in two steps. The second
      order rate constant for the first reaction is 4.3*10(8) M(-1) s(-1) . The rate of
      the second reaction is independent of the hydroxycobalamin concentration and is
      approximately 3.0*10(3) s(-1) . Evidence for formation of corrinoid complexes
      differing from cobalamin by the abstraction of two or four hydrogen atoms from
      the corrin macrocycle and lactone ring formation has been obtained by ultra-high
      performance liquid chromatography/high-resolution mass spectrometry (UHPLC/HRMS).
      A mechanism is proposed in which abstraction of a hydrogen atom by CO3 (.) (-)
      from a carbon atom not involved in the pi conjugation system of the corrin occurs
      in the first step, resulting in formation of a Co(III) C-centered radical that
      undergoes rapid intramolecular electron transfer to form the corresponding Co(II)
      carbocation complex for about 50 % of these complexes. Subsequent competing
      pathways lead to formation of corrinoid complexes with two fewer hydrogen atoms
      and lactone derivatives of B12 . Our results demonstrate the potential of UHPLC
      combined with HRMS in the separation and identification of tetrapyrrole
      macrocycles with minor modifications from their parent molecule.

PMID- 25760982
TI  - Protein identification from dried nipple aspirate fluid on Guthrie cards using
      mass spectrometry.
AB  - Nipple aspirate fluid (NAF) requires investigation as a potential source of
      biomarkers for early diagnosis or risk assessment in breast cancer and other
      breast disorders. The present study demonstrated that proteins were easily
      extracted from dried NAF spots on Guthrie cards and were suitable for mass
      spectrometry analysis. NAF was obtained from 80 women, collected on Guthrie
      cards, between 2007 and 2010. The NAF-proteins were extracted from the card by
      incubating the card in water. These proteins were then quantified and separated
      using one-dimensional, 12% SDS-PAGE, gel electrophoresis and on high-resolution
      gradient gels at different concentrations (4-12, 8-16 and 4-20%). The bands with
      the most abundant proteins were excised from the gradient gels and the proteins
      were identified by liquid chromatography quadrupole time of flight.
      Immunoglobulins, Zn-alpha2-glicoprotein, apoliprotein D and prolactin inducible
      protein were among those identified. The NAF-Guthrie card collection method has
      not been applied previously, however, NAF proteins have been identified using
      other collecting techniques, confirming the feasibility of the NAF Guthrie card
      collection method for analyzing the proteins within NAF. The NAF-Guthrie card
      collecting method has multiple advantages, including being inexpensive, non
      invasive, reliable and painless, and the cards can be stored at room temperature.
      Examining NAF may assist in identifying individuals at a higher risk of breast
      cancer and in improving patient prognosis.

PMID- 25760984
TI  - Impact of endometriomas and their removal on ovarian reserve.
AB  - PURPOSE OF REVIEW: The effect of endometrioma on ovulatory function and ovarian
      reserve was unclear. Conflicting opinions exist regarding effect of endometrioma
      excision on ovarian reserve. RECENT FINDINGS: Endometriomas do not seem to affect
      ovulatory function. Women with endometrioma have lower antral follicle count and
      serum anti-Mullerian hormone levels than age-matched healthy controls. There is
      high-quality evidence suggesting a significant decline in serum anti-Mullerian
      hormone levels following endometrioma excision. However, a similarly significant
      decline in antral follicle count is not demonstrated. Cauterization seems to be a
      contributing factor to ovarian damage and suturing the cyst bed could perhaps be
      a better alternative. SUMMARY: It seems prudent to warn patients regarding loss
      of ovarian reserve following endometrioma excision. Surgeons should cautiously
      limit the use of cauterization following stripping of endometrioma. Well designed
      studies comparing effect of various haemostatic measures on ovarian reserve are
      needed.

PMID- 25760983
TI  - Pulmonologist involvement, stage-specific treatment, and survival in adults with
      non-small cell lung cancer and chronic obstructive pulmonary disease.
AB  - RATIONALE: Up to 80% of patients with lung cancer have comorbid chronic
      obstructive pulmonary disease (COPD). Many of them are poor candidates for stage
      specific lung cancer treatment due to diminished lung function and poor
      functional status, and many forego treatment. The negative effect of COPD may be
      moderated by pulmonologist-guided management. OBJECTIVES: This study examined the
      association between pulmonologist management and the probability of receiving the
      recommended stage-specific treatment modality and overall survival among patients
      with non-small cell lung cancer (NSCLC) with preexisting COPD. METHODS: Early-
      and advanced-stage NSCLC cases diagnosed between 2002 and 2005 with a prior COPD
      diagnosis (3-24 months before NSCLC diagnosis) were identified in Surveillance,
      Epidemiology, and End Results tumor registry data linked to Medicare claims.
      Study outcomes included receipt of recommended stage-specific treatment (surgical
      resection for early-stage NSCLC and chemotherapy for advanced-stage NSCLC
      [advNSCLC]) and overall survival. Pulmonologist management was considered present
      if one or more Evaluation and Management visit claims with pulmonologist
      specialty were observed within 6 months after NSCLC diagnosis. Stage-specific
      multivariate logistic regression tested association between pulmonologist
      management and treatment received. Cox proportional hazard models examined the
      independent association between pulmonologist care and mortality. Two-stage
      residual inclusion instrumental variable (2SRI-IV) analyses tested and adjusted
      for potential confounding based on unobserved factors or measurement error.
      MEASUREMENTS AND MAIN RESULTS: The cohorts included 5,488 patients with early
      stage NSCLC and 6,426 patients with advNSCLC disease with preexisting COPD.
      Pulmonologist management was recorded for 54.9% of patients with early stage
      NSCLC and 35.7% of patients with advNSCLC. Of those patients with pulmonologist
      involvement, 58.5% of patients with early NSCLC received surgical resection, and
      43.6% of patients with advNSCLC received chemotherapy. Pulmonologist management
      post NSCLC diagnosis was associated with increased surgical resection rates (odds
      ratio, 1.26; 95% confidence interval, 1.11-1.45) for early NSCLC and increased
      chemotherapy rates (odds ratio, 1.88; 95% confidence interval, 1.67-2.10) for
      advNSCLC. Pulmonologist management was also associated with reduced mortality
      risk for patients with early-stage NSCLC but not AdvNSCLC. CONCLUSIONS:
      Pulmonologist management had a positive association with rates of stage-specific
      treatment in both groups and overall survival in early-stage NSCLC. These results
      provide preliminary support for the recently published guidelines emphasizing the
      role of pulmonologists in lung cancer management.

PMID- 25760985
TI  - Chitosan oligosaccharides in combination with Agaricus blazei Murill extract
      reduces hepatoma formation in mice with severe combined immunodeficiency.
AB  - Chitosan and Agaricus blazei Murill (ABM) extracts possess antitumor activities.
      The aim of the present study was to investigate whether chitosan, ABM extract or
      the two in combination were effective against tumors in tumor-bearing mice. The
      mice were subcutaneously injected with SK-Hep 1 cells and were then were divided
      into the following six groups: Group 1, control group; group 2, chitosan 5
      mg/kg/day; group 3, chitosan 20 mg/kg/day; group 4, ABM (246 mg/kg/day) and
      chitosan (5 mg/kg/day) combined; group 5, ABM (984 mg/kg/day) and chitosan (20
      mg/kg/day) combined; and group 6, ABM (984 mg/kg/day). The mice were treated with
      the different concentrations of chitosan, ABM or combinations of the two for 6
      weeks. The levels of glutamic oxaloacetic transaminase (GOT), glutamic pyruvic
      transaminase (GPT) and vascular endothelial growth factor (VEGF), and tissue
      histopathological features were examined in the surviving animals. Based on the
      results of the investigation, the treatments performed in groups 2, 3 and 4 were
      identified as being capable of reducing the weights of the tumors, however, group
      4, which was treated with chitosan (5 mg/kg/day) in combination with ABM (246
      mg/kg/day) was able to reduce the levels of GOT and VEGF. As a result, treatment
      with chitosan in combination with ABM may offer potential in cancer therapy and
      requires further investigation.

PMID- 25760986
TI  - Effects of pinacidil on changes to the microenvironment around the incision site,
      of a skin/muscle incision and retraction, in a rat model of postoperative pain.
AB  - The aim of the present study was to evaluate the influence of the
      microenvironment around an incision site, on peripheral and central
      sensitization. The effects of pinacidil activation of ATP-sensitive potassium
      (KATP) channels prior to skin/muscle incision and retraction (SMIR) surgery were
      assessed. A total of 24 male Sprague Dawley rats were randomly assigned to four
      groups: Control, sham (incision operation), SMIR (incision plus retraction 1 h
      after the skin/muscle incision) and pinacidil (SMIR plus pinacidil). The rats in
      the pinacidil group were intraperitoneally injected with pinacidil prior to the
      SMIR procedure. The mechanical withdrawal threshold (MWT) was determined at each
      time point. The microvessel density (MVD) value was determined by
      immunohistochemistry, and western blotting was performed to analyze the relative
      protein expression levels of nerve growth factor (NGF), glucose transporter
      protein-1 (GLUT1) and C-jun N-terminal kinases. There was a significant reduction
      in the levels of MVD, GLUT1 and MWT following SMIR surgery as compared with the
      incision alone, and a significant increase in the NGF protein expression levels.
      In the SMIR group, the MVD value was significantly increased seven days after
      surgery, as compared with three days after surgery. Additionally, intraperitoneal
      administration of pinacidil prior to the SMIR surgery inhibited the SMIR-induced
      reduction in MWT and MVD and attenuated the SMIR-induced GLUT1 reduction. The
      results of the present study suggest that the microenvironment around an incision
      site may affect the development of peripheral and central sensitization. In
      addition, pinacidil had an inhibitory effect on the formation of the inflammatory
      microenvironment around the incision site through activation of KATP channels,
      thereby inhibiting peripheral and central sensitization.

PMID- 25760987
TI  - Preventive effects of a fermented dairy product against Alzheimer's disease and
      identification of a novel oleamide with enhanced microglial phagocytosis and anti
      inflammatory activity.
AB  - Despite the ever-increasing number of patients with dementia worldwide,
      fundamental therapeutic approaches to this condition have not been established.
      Epidemiological studies suggest that intake of fermented dairy products prevents
      cognitive decline in the elderly. However, the active compounds responsible for
      the effect remain to be elucidated. The present study aims to elucidate the
      preventive effects of dairy products on Alzheimer's disease and to identify the
      responsible component. Here, in a mouse model of Alzheimer's disease (5xFAD),
      intake of a dairy product fermented with Penicillium candidum had preventive
      effects on the disease by reducing the accumulation of amyloid beta (Abeta) and
      hippocampal inflammation (TNF-alpha and MIP-1alpha production), and enhancing
      hippocampal neurotrophic factors (BDNF and GDNF). A search for preventive
      substances in the fermented dairy product identified oleamide as a novel dual
      active component that enhanced microglial Abeta phagocytosis and anti
      inflammatory activity towards LPS stimulation in vitro and in vivo. During the
      fermentation, oleamide was synthesized from oleic acid, which is an abundant
      component of general dairy products owing to lipase enzymatic amidation. The
      present study has demonstrated the preventive effect of dairy products on
      Alzheimer's disease, which was previously reported only epidemiologically.
      Moreover, oleamide has been identified as an active component of dairy products
      that is considered to reduce Abeta accumulation via enhanced microglial
      phagocytosis, and to suppress microglial inflammation after Abeta deposition.
      Because fermented dairy products such as camembert cheese are easy to ingest
      safely as a daily meal, their consumption might represent a preventive strategy
      for dementia. 

PMID- 25760988
TI  - Myocardial infarct size and mortality depend on the time of day-a large
      multicenter study.
AB  - BACKGROUND: Different studies have shown circadian variation of ischemic burden
      among patients with ST-Elevation Myocardial Infarction (STEMI), but with
      controversial results. The aim of this study was to analyze circadian variation
      of myocardial infarction size and in-hospital mortality in a large multicenter
      registry. METHODS: This retrospective, registry-based study was based on data
      from AMIS Plus, a large multicenter Swiss registry of patients who suffered
      myocardial infarction between 1999 and 2013. Peak creatine kinase (CK) was used
      as a proxy measure for myocardial infarction size. Associations between peak CK,
      in-hospital mortality, and the time of day at symptom onset were modelled using
      polynomial-harmonic regression methods. RESULTS: 6,223 STEMI patients were
      admitted to 82 acute-care hospitals in Switzerland and treated with primary
      angioplasty within six hours of symptom onset. Only the 24-hour harmonic was
      significantly associated with peak CK (p = 0.0001). The maximum average peak CK
      value (2,315 U/L) was for patients with symptom onset at 23:00, whereas the
      minimum average (2,017 U/L) was for onset at 11:00. The amplitude of variation
      was 298 U/L. In addition, no correlation was observed between ischemic time and
      circadian peak CK variation. Of the 6,223 patients, 223 (3.58%) died during index
      hospitalization. Remarkably, only the 24-hour harmonic was significantly
      associated with in-hospital mortality. The risk of death from STEMI was highest
      for patients with symptom onset at 00:00 and lowest for those with onset at
      12:00. DISCUSSION: As a part of this first large study of STEMI patients treated
      with primary angioplasty in Swiss hospitals, investigations confirmed a circadian
      pattern to both peak CK and in-hospital mortality which were independent of total
      ischemic time. Accordingly, this study proposes that symptom onset time be
      incorporated as a prognosis factor in patients with myocardial infarction.

PMID- 25760990
TI  - Universal Efficiency Improvement in Organic Solar Cells Based on a Poly(3
      hexylthiophene) Donor and an Indene-C60 Bisadduct Acceptor with Additional Donor
      Nanowires.
AB  - With poly(3-hexylthiophene) (P3HT) nanowire (NW) inclusion in active layers
      (ALs), organic solar cells (OSCs) based on P3HT donor and indene-C60 bisadduct
      (ICBA) acceptor showed power conversion efficiency (PCE) improvements for both
      bulk heterojunction (BHJ)- and bilayer (BL)-structure AL devices. The PCE
      increase was approximately 14 % for both types of P3HT:ICBA OSCs. However,
      improvements in short-circuit current density (Jsc ) were about 4.4 and 6.4 % for
      BHJ- and BL-type AL devices, respectively. A systematic study showed that the
      addition of P3HT NWs did not result in enhanced internal quantum efficiencies for
      either type of device. However, the difference in light-harvesting efficiency was
      important in accounting for Jsc variations. Interestingly, there was no
      correlation between Jsc and PCE variations, whereas the open-circuit voltage (Voc
      ) and fill factor (FF) showed correlations with the PCE. The variation in FF is
      discussed in terms of Voc and equivalent-circuit parameters based on a nonideal
      diode model. 

PMID- 25760989
TI  - Developmental block and programmed cell death in Bos indicus embryos: effects of
      protein supplementation source and developmental kinetics.
AB  - The aims of this study were to determine if the protein source of the medium
      influences zebu embryo development and if developmental kinetics, developmental
      block and programmed cell death are related. The culture medium was supplemented
      with either fetal calf serum or bovine serum albumin. The embryos were classified
      as Fast (n = 1,235) or Slow (n = 485) based on the time required to reach the
      fourth cell cycle (48 h and 90 h post insemination - hpi -, respectively). The
      Slow group was further separated into two groups: those presenting exactly 4
      cells at 48 hpi (Slow/4 cells) and those that reached the fourth cell cycle at 90
      hpi (Slow). Blastocyst quality, DNA fragmentation, mitochondrial membrane
      potential and signs of apoptosis or necrosis were evaluated. The Slow group had
      higher incidence of developmental block than the Fast group. The embryos
      supplemented with fetal calf serum had lower quality. DNA fragmentation and
      mitochondrial membrane potential were absent in embryos at 48 hpi but present at
      90 hpi. Early signs of apoptosis were more frequent in the Slow and Slow/4 cell
      groups than in the Fast group. We concluded that fetal calf serum reduces
      blastocyst development and quality, but the mechanism appears to be independent
      of DNA fragmentation. The apoptotic cells detected at 48 hpi reveal a possible
      mechanism of programmed cell death activation prior to genome activation. The
      apoptotic cells observed in the slow-developing embryos suggested a relationship
      between programmed cell death and embryonic developmental kinetics in zebu in
      vitro-produced embryos. 

PMID- 25760991
TI  - The clinical effectiveness and cost-effectiveness of treatments for idiopathic
      pulmonary fibrosis: a systematic review and economic evaluation.
AB  - BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a life-limiting lung disease
      that generally affects people over 60 years old. The main symptoms are shortness
      of breath and cough, and as the disease progresses there is a considerable impact
      on day-to-day life. Few treatments are currently available. OBJECTIVES: To
      conduct a systematic review of clinical effectiveness and an analysis of cost
      effectiveness of treatments for IPF based on an economic model informed by
      systematic reviews of cost-effectiveness and quality of life. DATA SOURCES:
      Eleven electronic bibliographic databases, including MEDLINE, EMBASE, Web of
      Science, and The Cochrane Library and the Centre for Reviews and Dissemination
      databases, were searched from database inception to July 2013. Reference lists of
      relevant publications were also checked and experts consulted. METHODS: Two
      reviewers independently screened references for the systematic reviews, extracted
      and checked data from the included studies and appraised their risk of bias. An
      advisory group was consulted about the choice of interventions until consensus
      was reached about eligibility. A narrative review with meta-analysis was
      undertaken, and a network meta-analysis (NMA) was performed. A decision-analytic
      Markov model was developed to estimate cost-effectiveness of pharmacological
      treatments for IPF. Parameter values were obtained from NMA and systematic
      reviews. Univariate and probabilistic sensitivity analyses were undertaken. The
      model perspective is NHS and Personal Social Services, and discount rate is 3.5%
      for costs and health benefits. RESULTS: Fourteen studies were included in the
      review of clinical effectiveness, of which one evaluated azathioprine, three N
      acetylcysteine (NAC) (alone or in combination), four pirfenidone, one BIBF 1120,
      one sildenafil, one thalidomide, two pulmonary rehabilitation, and one a disease
      management programme. Study quality was generally good, with a low risk of bias.
      The current evidence suggests that some treatments appear to be clinically
      effective. The model base-case results show increased survival for five
      pharmacological treatments, compared with best supportive care, at increased
      cost. General recommendations cannot be made of their cost-effectiveness owing to
      limitations in the evidence base. LIMITATIONS: Few direct comparisons of
      treatments were identified. An indirect comparison through a NMA was performed;
      however, caution is recommended in the interpretation of these results. In
      relation to the economic model, there is an assumption that pharmacological
      treatments have a constant effect on the relative rate of per cent predicted
      forced vital capacity decline. CONCLUSIONS: Few interventions have any
      statistically significant effect on IPF and a lack of studies on palliative care
      approaches was identified. Research is required into the effects of symptom
      control interventions, in particular pulmonary rehabilitation and thalidomide.
      Other research priorities include a well-conducted randomised controlled trial on
      inhaled NAC therapy and an updated evidence synthesis once the results of ongoing
      studies are reported. STUDY REGISTRATION: This study is registered as PROSPERO
      CRD42012002116. FUNDING: The National Institute for Health Research Health
      Technology Assessment programme.

PMID- 25760992
TI  - Foreword: lesbian studies in Canada.

PMID- 25760993
TI  - Everyday decolonization: living a decolonizing queer politics.
AB  - This article is a joint exploration of what decolonization looks like in everyday
      interactions within our partnerships, families, and friendships on unceded Coast
      Salish territories. Stories from the authors--two cisgender queer women, one of
      whom is Indigenous and one of whom is a White settler--highlight intimate
      practices of allyship and decolonization that are often made invisible when
      activism is seen as only taking place in "public" spaces such as community
      coalitions. The tensions and possibilities within these intimate geographies of
      allyship comprise a decolonial queer praxis that is materialized in the spatial
      relations of our homes and families.

PMID- 25760994
TI  - Lesbians in the city: mobilities and relational geographies.
AB  - This article examines contemporary lesbians' (and queer women's) urban
      geographies, drawing from empirical research on Toronto, Canada and Sydney,
      Australia. Our argument is grounded in research highlighting lesbians'
      distinctive urban experiences: lesbians have both participated in gay villages
      and gay male spaces and, importantly, carved out their own urban places,
      including commercial and residential concentrations. In this article we use new
      mobilities scholarship to delineate historical and contemporary relational
      geographies materializing since World War II, which continue to rewrite lesbians'
      and queer women's inhabitation and experiences of urban landscapes in Toronto and
      Sydney. 

PMID- 25760995
TI  - Entering the urban frame: early lesbian activism and public space in Montreal.
AB  - This article examines the spatial strategies used by Montreal lesbian activists
      in the 1970s and 1980s to fight for the lesbian "right to the city." After
      situating lesbian public activism within Henri Lefebvre's ideal of spatial
      justice, this article provides case studies of four moments during which Montreal
      lesbian activists joined or initiated public demonstrations as lesbians. The
      focus is on the multiple ways in which lesbian activists performed politicized
      lesbian identities in urban public spaces. Their spatial strategies in this first
      era of the lesbian and gay rights movement provide an alternative account of
      claiming lesbian, gay, bisexual, transgender, and queer rights to the
      heterosexual city. 

PMID- 25760996
TI  - Lesbian mommy blogging in Canada: documenting subtle homophobia in Canadian
      society and building community online.
AB  - This article analyzes how lesbian mommy bloggers in Canada are using their blogs
      as forums for self-expression and a means to form community, as they record their
      unique experiences as queer parents. Further, it argues that lesbian mommy
      blogging is documenting a subtle form of homophobia that exists in Canada in
      terms of social acceptance. Although there is legal acceptance of queer families,
      society has not necessarily caught up with the law. These blogs show that lesbian
      parents in Canada still struggle with issues of equality, including difficulties
      being "out," invisibility, and having to advocate for the non-birth parent. 

PMID- 25760997
TI  - The demand to progress: critical nostalgia in LGBTQ cultural memory.
AB  - This article argues that, while representations of tragic lesbian, gay, bisexual,
      transgender, and queer (LGBTQ) histories are disseminated widely, positive
      aspects of the past must be largely pushed out of the cultural imaginary to
      support a vision of the present in which sexual rights and freedoms have been
      achieved. It proposes that this view relies on a linear progress narrative
      wherein the experiences of LGBTQ people are held as consistently improving over
      time. In considering the construction of cultural memory through popular media
      and art, it claims a nostalgic turn to the past as a useful political tool for
      dismantling the pacifying aspects of the present. 

PMID- 25760998
TI  - Pride and prejudice: factors affecting school attachment among lesbian, bisexual,
      and heterosexual girls.
AB  - School attachment is often regarded as a key measure in gauging the integration
      and wellbeing of students. Previous research suggests that levels of school
      attachment are generally lower among sexual minority students, but most studies
      focus on between-gender comparisons and do not conduct within-gender analyses.
      Using data from the First National Climate Survey on Homophobia and Transphobia
      in Canadian schools, this study set out to empirically analyze what, if any,
      differences exist among lesbian, bisexual, and heterosexual female students when
      assessing the relationship between homophobic and gender-negative language,
      feelings of safety, harassment/direct victimization, and school climate on school
      attachment. Bivariate and multivariate findings suggest that there are key
      differences among female students in terms of school attachment. 

PMID- 25760999
TI  - Lithic landscapes: early human impact from stone tool production on the central
      Saharan environment.
AB  - Humans have had a major impact on the environment. This has been particularly
      intense in the last millennium but has been noticeable since the development of
      food production and the associated higher population densities in the last 10,000
      years. The use of fire and over-exploitation of large mammals has also been
      recognized as having an effect on the world's ecology, going back perhaps 100,000
      years or more. Here we report on an earlier anthropogenic environmental change.
      The use of stone tools, which dates back over 2.5 million years, and the
      subsequent evolution of a technologically-dependent lineage required the
      exploitation of very large quantities of rock. However, measures of the impact of
      hominin stone exploitation are rare and inherently difficult. The Messak
      Settafet, a sandstone massif in the Central Sahara (Libya), is littered with
      Pleistocene stone tools on an unprecedented scale and is, in effect, a man-made
      landscape. Surveys showed that parts of the Messak Settafet have as much as 75
      lithics per square metre and that this fractured debris is a dominant element of
      the environment. The type of stone tools--Acheulean and Middle Stone Age-
      indicates that extensive stone tool manufacture occurred over the last half
      million years or more. The lithic-strewn pavement created by this ancient stone
      tool manufacture possibly represents the earliest human environmental impact at a
      landscape scale and is an example of anthropogenic change. The nature of the
      lithics and inferred age may suggest that hominins other than modern humans were
      capable of unintentionally modifying their environment. The scale of debris also
      indicates the significance of stone as a critical resource for hominins and so
      provides insights into a novel evolutionary ecology.

PMID- 25761000
TI  - Simulating activities of daily living with finite element analysis improves
      fracture prediction for patients with metastatic femoral lesions.
AB  - Predicting fracture risk for patients with metastatic femoral lesions remains an
      important clinical problem. Mirels' criterion remains the most formalized
      radiographic scoring system with good sensitivity (correctly identifying clinical
      fractures) but relatively poor specificity (correctly identify cases that do not
      fracture). A series of patients with metastatic femoral lesions had Computed
      Tomography (CT) scans, were followed prospectively for 4 months, and categorized
      into fracture (n = 5), non-fracture (n = 28), or stabilized (n = 11) groups. CT
      based-Finite Element (FE) modeling was used to predict fracture for these cases
      using axial compression (AC), level walking (LW), and aggressive stair ascent
      (ASA) loading conditions. The FE predicted fracture force was greater for the non
      fracture compared to the fracture group for all loading cases. The ability of the
      FE models to predict fracture cases (sensitivity) was similar for the groups
      (Mirels, AC, LW: 80%, ASA: 100%). The ability of the models to correctly predict
      the non-fracture cases (specificity) was improved for AC (71%) and LW (86%)
      loading conditions, when compared to Mirels specificity (43%), but poorer for the
      ASA (21%) conditions. The results suggest that FE models that assess fracture
      risk using LW conditions can improve fracture prediction over Mirels scoring in a
      clinical population.

PMID- 25761001
TI  - Preconscious prediction of a driver's decision using intracranial recordings.
AB  - While driving, we make numerous conscious decisions such as route and turn
      direction selection. Although drivers are held responsible, the neural processes
      that govern such decisions are not clear. We recorded intracranial EEG signals
      from six patients engaged in a computer-based driving simulator. Patients decided
      which way to turn (left/right) and subsequently reported the time of the
      decision. We show that power modulations of gamma band oscillations (30-100 Hz)
      preceding the reported time of decision (up to 5.5 sec) allow prediction of
      decision content with high accuracy (up to 82.4%) on a trial-by-trial basis,
      irrespective of subsequent motor output. Moreover, these modulations exhibited a
      spatiotemporal gradient, differentiating left/right decisions earliest in
      premotor cortices and later in more anterior and lateral regions. Our results
      suggest a preconscious role for the premotor cortices in early stages of decision
      making, which permits foreseeing and perhaps modifying the content of real-life
      human choices before they are consciously made. 

PMID- 25761002
TI  - Feel between the lines: implied emotion in sentence comprehension.
AB  - This study investigated the brain regions for the comprehension of implied
      emotion in sentences. Participants read negative sentences without negative
      words, for example, "The boy fell asleep and never woke up again," and their
      neutral counterparts "The boy stood up and grabbed his bag." This kind of
      negative sentence allows us to examine implied emotion derived at the sentence
      level, without associative emotion coming from word retrieval. We found that
      implied emotion in sentences, relative to neutral sentences, led to activation in
      some emotion-related areas, including the medial prefrontal cortex, the amygdala,
      and the insula, as well as certain language-related areas, including the inferior
      frontal gyrus, which has been implicated in combinatorial processing. These
      results suggest that the emotional network involved in implied emotion is
      intricately related to the network for combinatorial processing in language,
      supporting the view that sentence meaning is more than simply concatenating the
      meanings of its lexical building blocks. 

PMID- 25761003
TI  - Seeing the same words differently: the time course of automaticity and top-down
      intention in reading.
AB  - We investigated how linguistic intention affects the time course of visual word
      recognition by comparing the brain's electrophysiological response to a word's
      lexical frequency, a well-established psycholinguistic marker of lexical access,
      when participants actively retrieve the meaning of the written input (semantic
      categorization) versus a situation where no language processing is necessary (ink
      color categorization). In the semantic task, the ERPs elicited by high-frequency
      words started to diverge from those elicited by low-frequency words as early as
      120 msec after stimulus onset. On the other hand, when categorizing the colored
      font of the very same words in the color task, word frequency did not modulate
      ERPs until some 100 msec later (220 msec poststimulus onset) and did so for a
      shorter period and with a smaller scalp distribution. The results demonstrate
      that, although written words indeed elicit automatic recognition processes in the
      brain, the speed and quality of lexical processing critically depends on the top
      down intention to engage in a linguistic task. 

PMID- 25761004
TI  - Practice structure improves unconscious transitional memories by increasing
      synchrony in a premotor network.
AB  - Sequence learning relies on formation of unconscious transitional and conscious
      ordinal memories. The influence of practice type on formation of these memories
      that compose skill and systems level neural substrates is not known. Here, we
      studied learning of transitional and ordinal memories in participants trained on
      motor sequences while scanned using fMRI. Practice structure was varied or
      grouped (mixing or grouping sequences during training, respectively). Memory was
      assessed 30 min and 1 week later. Varied practice improved transitional memory
      and enhanced coupling of the dorsal premotor cortex with thalamus, cerebellum,
      and lingual and cingulate regions and greater transitional memory correlated with
      this coupling. Thus, varied practice improves unconscious transitional memories
      in proportion to coupling within a cortico-subcortical network linked to premotor
      cortex. This result indicates that practice structure influences unconscious
      transitional memory formation and identifies underlying systems level mechanisms.

PMID- 25761005
TI  - The devil is in the detail: brain dynamics in preparation for a global-local
      task.
AB  - When analyzing visual scenes, it is sometimes important to determine the relevant
      "grain" size. Attention control mechanisms may help direct our processing to the
      intended grain size. Here we used the event-related optical signal, a method
      possessing high temporal and spatial resolution, to examine the involvement of
      brain structures within the dorsal attention network (DAN) and the visual
      processing network (VPN) in preparation for the appropriate level of analysis.
      Behavioral data indicate that the small features of a hierarchical stimulus
      (local condition) are more difficult to process than the large features (global
      condition). Consistent with this finding, cues predicting a local trial were
      associated with greater DAN activation. This activity was bilateral but more
      pronounced in the left hemisphere, where it showed a frontal-to-parietal
      progression over time. Furthermore, the amount of DAN activation, especially in
      the left hemisphere and in parietal regions, was predictive of subsequent
      performance. Although local cues elicited left-lateralized DAN activity, no
      preponderantly right activity was observed for global cues; however, the data
      indicated an interaction between level of analysis (local vs. global) and
      hemisphere in VPN. They further showed that local processing involves structures
      in the ventral VPN, whereas global processing involves structures in the dorsal
      VPN. These results indicate that in our study preparation for analyzing different
      size features is an asymmetric process, in which greater preparation is required
      to focus on small rather than large features, perhaps because of their lesser
      salience. This preparation involves the same DAN used for other attention control
      operations. 

PMID- 25761006
TI  - The inclusion of functional connectivity information into fMRI-based
      neurofeedback improves its efficacy in the reduction of cigarette cravings.
AB  - Real-time fMRI (rtfMRI) neurofeedback (NF) facilitates volitional control over
      brain activity and the modulation of associated mental functions. The NF signals
      of traditional rtfMRI-NF studies predominantly reflect neuronal activity within
      ROIs. In this study, we describe a novel rtfMRI-NF approach that includes a
      functional connectivity (FC) component in the NF signal (FC-added rtfMRI-NF). We
      estimated the efficacy of the FC-added rtfMRI-NF method by applying it to
      nicotine-dependent heavy smokers in an effort to reduce cigarette craving. ACC
      and medial pFC as well as the posterior cingulate cortex and precuneus are
      associated with cigarette craving and were chosen as ROIs. Fourteen heavy smokers
      were randomly assigned to receive one of two types of NF: traditional activity
      based rtfMRI-NF or FC-added rtfMRI-NF. Participants received rtfMRI-NF training
      during two separate visits after overnight smoking cessation, and cigarette
      craving score was assessed. The FC-added rtfMRI-NF resulted in greater neuronal
      activity and increased FC between the targeted ROIs than the traditional activity
      based rtfMRI-NF and resulted in lower craving score. In the FC-added rtfMRI-NF
      condition, the average of neuronal activity and FC was tightly associated with
      craving score (Bonferroni-corrected p = .028). However, in the activity-based
      rtfMRI-NF condition, no association was detected (uncorrected p > .081). Non
      rtfMRI data analysis also showed enhanced neuronal activity and FC with FC-added
      NF than with activity-based NF. These results demonstrate that FC-added rtfMRI-NF
      facilitates greater volitional control over brain activity and connectivity and
      greater modulation of mental function than activity-based rtfMRI-NF. 

PMID- 25761007
TI  - Changes in theta and beta oscillations as signatures of novel word consolidation.
AB  - The complementary learning systems account of word learning states that novel
      words, like other types of memories, undergo an offline consolidation process
      during which they are gradually integrated into the neocortical memory network. A
      fundamental change in the neural representation of a novel word should therefore
      occur in the hours after learning. The present EEG study tested this hypothesis
      by investigating whether novel words learned before a 24-hr consolidation period
      elicited more word-like oscillatory responses than novel words learned
      immediately before testing. In line with previous studies indicating that theta
      synchronization reflects lexical access, unfamiliar novel words elicited lower
      power in the theta band (4-8 Hz) than existing words. Recently learned words
      still showed a marginally lower theta increase than existing words, but theta
      responses to novel words that had been acquired 24 hr earlier were
      indistinguishable from responses to existing words. Consistent with evidence that
      beta desynchronization (16-21 Hz) is related to lexical-semantic processing, we
      found that both unfamiliar and recently learned novel words elicited less beta
      desynchronization than existing words. In contrast, no difference was found
      between novel words learned 24 hr earlier and existing words. These data
      therefore suggest that an offline consolidation period enables novel words to
      acquire lexically integrated, word-like neural representations.

PMID- 25761008
TI  - Bioinspired organocatalytic aerobic C-H oxidation of amines with an ortho-quinone
      catalyst.
AB  - A simple bioinspired ortho-quinone catalyst for the aerobic oxidative
      dehydrogenation of amines to imines is reported. Without any metal cocatalysts,
      the identified optimal ortho-quinone catalyst enables the oxidations of alpha
      branched primary amines and cyclic secondary amines. Mechanistic studies have
      disclosed the origins of different performances of ortho-quinone vs para-quinone
      in biomimetic amine oxidations. 

PMID- 25761009
TI  - Conformational preferences of DNA following damage by aristolochic acids:
      Structural and energetic insights into the different mutagenic potential of the
      ALI and ALII-N(6)-dA adducts.
AB  - Aristolochic acids (AAI and AAII), produced by the Aristolochiaceae family of
      plants, are classified as group I (human) carcinogens by the International Agency
      for Research on Cancer. These acids are metabolized in cells to yield
      aristolactams (ALI and ALII, respectively), which further form bulky adducts with
      the purine nucleobases. Specifically, the adenine lesions are more persistent in
      cells and have been associated with chronic renal diseases and related
      carcinogenesis. To understand the structural basis of the nephrotoxicity induced
      by AAs, the ALI-N(6)-dA and ALII-N(6)-dA lesions are systematically studied using
      computational methods. Density functional theory calculations indicate that the
      aristolactam moiety intrinsically prefers a planar conformation with respect to
      adenine. Nucleoside and nucleotide models suggest that the anti and syn
      orientations about the glycosidic bond are isoenergetic for both adducts.
      Molecular dynamics simulations and free energy calculations reveal that the anti
      base-displaced intercalated conformation is the most stable conformer for both
      types of AL-N(6)-dA adducted DNA, which agrees with previous experimental work on
      the ALII-N(6)-dA adduct and thereby validates our approach. Interestingly, this
      conformer differs from the dominant conformations adopted by other N6-linked
      adenine lesions, including those derived from polycyclic aromatic hydrocarbons.
      Furthermore, the second most stable syn base-displaced intercalated conformation
      lies closer in energy to the anti base-displaced intercalated conformation for
      ALI-N(6)-dA compared to ALII-N(6)-dA. This indicates that a mixture of
      conformations may be detectable for ALI-N(6)-dA in DNA. If this enhanced
      conformational flexibility of double-stranded DNA persists when bound to a lesion
      bypass polymerase, this provides a possible structural explanation for the
      previously observed greater nephrotoxic potential for the ALI versus ALII-N(6)-dA
      adduct. In addition, the structural characteristics of the preferred
      conformations of adducted DNA explain the resistance of these adducts to repair
      and thereby add to our current understanding of the toxicity of AAs within living
      cells.

PMID- 25761010
TI  - Chitosan: a propitious biopolymer for drug delivery.
AB  - Scientists have always been interested in the use of natural polymers for drug
      delivery. Chitosan, being a natural cationic polysaccharide has received a great
      deal of attention in the past few years. It is obtained by deacetylation of
      chitin and is regarded as the second most ubiquitous polymer subsequent to
      cellulose on earth. Unlike other natural polymers, the cationic charge possessed
      by chitosan is accountable for imparting interesting physical and chemical
      properties. Chitosan has been widely exploited for its mucoadhesive character,
      permeation enhancing properties and controlled release of drugs. Moreover it's
      non-toxic, biocompatible and biodegradable properties make it a good candidate
      for novel drug delivery system. This review provides an insight on various
      chitosan based formulations for drug delivery. Some of the current applications
      of chitosan in areas like ophthalmic, nasal, buccal, sublingual, gastro
      retentive, pulmonary, transdermal, colon-specific and vaginal drug delivery have
      been discussed. In addition, active targeting of drugs to tumor cells using
      chitosan has been described. Lastly a brief section covering the safety aspects
      of chitosan has also been reviewed. 

PMID- 25761011
TI  - Genetic interaction between GROWTH-REGULATING FACTOR and CUP-SHAPED COTYLEDON in
      organ separation.
AB  - The Arabidopsis thaliana GROWTH-REGULATING FACTOR (GRF) gene family comprises 9
      members and encodes a class of transcription factors. We previously demonstrated
      that GRF genes played an essential role in formation of the boundary region
      between cotyledons, since their loss-of-function mutants developed fused
      cotyledons. Our present study shows that the grf mutants display fused floral
      organs as well. Such fusion phenotypes of embryonic and post-embryonic floral
      organs are highly reminiscent of the cup-shaped cotyledon (cuc) mutants. In order
      to test a genetic interaction between GRFs and CUCs, we constructed cuc1
      grf1/2/3, cuc2 grf1/2/3, and cuc3 grf1/2/3 quadruple mutants, and found that the
      mutants showed dramatic increases in cotyledon fusion as well as floral organ
      fusion. The results suggest that the signaling pathway of GRFs may be genetically
      associated with that of CUCs in the organ separation process. 

PMID- 25761012
TI  - The quest for the diagnosis.

PMID- 25761013
TI  - [Cured, but not quite well].

PMID- 25761014
TI  - [From child to adult].

PMID- 25761015
TI  - Health and mortality - two sides of the same coin?

PMID- 25761016
TI  - [Re: Occupational lung cancer in Sor-Trondelag county].

PMID- 25761017
TI  - [S. Slastad and colleagues reply].

PMID- 25761018
TI  - [Re: In momentous development?].

PMID- 25761021
TI  - [Re: Seclusion in emergency psychiatry].

PMID- 25761022
TI  - [Cancer--not just bad luck!].

PMID- 25761023
TI  - [Help us with high chairs].

PMID- 25761024
TI  - [Special outpatient clinic for skeletal dysplasias].

PMID- 25761027
TI  - [Adolescents with cerebral palsy and their contact with the GP and the
      habilitative services].
AB  - BACKGROUND: Cerebral palsy (CP) often entails a need for health and social
      services throughout life. Upon scrutiny, it has been found that the transition
      from services for children and adolescents to services for adults is particularly
      challenging. The study investigates contact between adolescents with CP and their
      GPs/habilitative services up to and after the age of 18 years, and the percentage
      who have an individual habilitation plan (IHP). MATERIAL AND METHOD: An attempt
      was made to identify all those with CP born in 1992 and 1993 and resident in
      southeast Norway. Seventy-four patients were included (time point I, interview
      and clinical examination). Forty-two (57%) responded at the follow-up examination
      (time point II, questionnaire). RESULTS: At time point I, 35 (47%) of the
      adolescents had consulted their GP in the past year, 49 (66%) had been in contact
      with the habilitative services, and 42 (57%) had an IHP. Twenty-eight (38%) used
      mobility aids. Use of mobility aids gave lower odds of consultation with the GP.
      Longer distances from home to the habilitative services gave lower odds of
      contact with both the GP and the habilitative services. Five adolescents with
      mobility aids did not have an IHP. At time point II, the percentage who had
      consulted their GP had increased somewhat, the percentage who had been in contact
      with the habilitative services had reduced, and the percentage who had an IHP was
      unchanged. INTERPRETATION: The findings reinforce the assumption that the health
      services provided to disabled adolescents are less locally based and less well
      coordinated than is supposed, and that there may be geographical differences in
      the service offered.

PMID- 25761028
TI  - Self-rated health and mortality in different occupational classes and income
      groups in Nord-Trondelag County, Norway.
AB  - BACKGROUND: People with a lower socioeconomic position have a higher the
      prevalence of most self-rated health problems. In this article we ask whether
      this may be attributed to self-rated health not reflecting actual health,
      understood as mortality, in different socioeconomic groups. MATERIAL AND METHOD:
      For the study we used data from the Nord-Trondelag Health Study 1984-86 (HUNT1),
      in which the county's entire adult population aged 20 years and above were
      invited to participate. The association between self-rated health and mortality
      in different occupational classes and income groups was analysed. The analysis
      corrected for age, chronic disease, functional impairment and lifestyle factors.
      RESULTS: The association between self-rated health and mortality was of the same
      order of magnitude for the occupational classes and income groups, but persons
      without work/income and with poor self-rated health stood out. Compared with
      persons in the highest socioeconomic class, unemployed men had a hazard ratio for
      death that was three times higher in the follow-up period. For women with no
      income, the ratio was twice as high. INTERPRETATION Self-rated health and
      mortality largely conform to the different socioeconomic strata. This supports
      the perception that socioeconomic differences in health are a reality and
      represent a significant challenge nationally. Our results also increase the
      credibility of findings from other studies that use self-reported health in
      surveys to measure differences and identify the mechanisms that create them.

PMID- 25761029
TI  - [Cerebral edema after status epilepticus].

PMID- 25761030
TI  - [Hereditary zinc deficiency].

PMID- 25761031
TI  - [A child with cramps and sudden vision loss during chemotherapy].

PMID- 25761032
TI  - [A boy with a wound on his finger that would not heal].

PMID- 25761033
TI  - Melanoma incidence on the rise again.

PMID- 25761034
TI  - [Academia and the academy].

PMID- 25761045
TI  - A competing risk analysis for hospital length of stay in patients with burns.
AB  - IMPORTANCE: Current outcome predictors for illness and injury are measured at a
      single time point-admission. However, patient prognosis often changes during
      hospitalization, limiting the usefulness of those predictions. Accurate depiction
      of the dynamic interaction between competing events during hospitalization may
      enable real-time outcome assessment. OBJECTIVE: To determine how the effects of
      burn outcome predictors (ie, age, total body surface area burn, and inhalation
      injury) and the outcomes of interest (ie, mortality and length of stay) vary as a
      function of time throughout hospitalization. DESIGN, SETTING, AND PARTICIPANTS:
      In this retrospective study, we used the American Burn Association's National
      Burn Repository, containing outcomes and patient and injury characteristics, to
      identify 95 579 patients admitted with an acute burn injury to 80 tertiary
      American Burn Association burn centers from 2000 through 2009. We applied
      competing risk statistical methods to analyze patient outcomes. MAIN OUTCOMES AND
      MEASURES: We estimated the cause-specific hazard rates for death and discharge to
      assess how the instantaneous risk of these events changed across time. We further
      evaluated the varying effects of patient age, total body surface area burn, and
      inhalation injury on the probability of discharge and death across time. RESULTS:
      Maximum length of stay among patients who died was 270 days and 731 days among
      those discharged. Total body surface area, age, and inhalation injury had
      significant effects on the subdistribution hazard for discharge (P < .001); these
      effects varied across time (P < .002). Burn size (coefficient -0.046) determined
      early outcomes, while age (coefficient -0.034) determined outcomes later in the
      hospitalization. Inhalation injury (coefficient -0.622) played a variable role in
      survival and hospital length of stay. CONCLUSIONS AND RELEVANCE: Real-time
      measurement of dynamic interrelationships among burn outcome predictors using
      competing risk analysis demonstrated that the key factors influencing outcomes
      differed throughout hospitalization. Further application of this analytic
      technique to other injury or illness types may improve assessment of outcomes.

PMID- 25761046
TI  - Neutron reflection study of the adsorption of the phosphate surfactant NaDEHP
      onto alumina from water.
AB  - The adsorption of a phosphorus analogue of the surfactant AOT, sodium bis(2
      ethylhexyl) phosphate (NaDEHP), at the water/alumina interface is described. The
      material is found to adsorb as an essentially water-free bilayer from neutron
      reflection measurements. This is similar to the behavior of AOT under comparable
      conditions, although AOT forms a thicker, more hydrated layer. The NaDEHP shows
      rather little variation with added salt, but a small thickening of the layer on
      increasing the pH, in contrast to the behavior of AOT. 

PMID- 25761048
TI  - Effect of body mass index and albumin on mortality rates for adult African
      American hemodialysis patients.
AB  - PURPOSE: The purpose of this retrospective descriptive study was to investigate
      if body mass index (BMI) and serum albumin (SA) impacted mortality rates in adult
      African-American patients on hemodialysis (HD). DATA SOURCES: Records of 204
      patients on HD (N = 204) from a clinic in the metropolitan Detroit area were
      examined for the period January 1, 2007-December 31, 2012 to determine the
      relationship of BMI and SA on mortality rates in this population. Logistics
      regression was utilized to analyze the association of several risk factors (BMI
      and SA) on survival (mortality rates). CONCLUSION: Research findings from this
      study demonstrated that both undernourishment (being underweight; BMI < 23
      kg/m(2) ) and hypoalbuminemia (<3.2g/dL) were strong predictors of death in
      patients on HD. However, obesity provided a survival advantage for adult African
      American patients on HD (p = .030). Patients with higher SA levels also survived
      longer (p < .001). IMPLICATIONS FOR PRACTICE: Advanced practice nurses (APNs)
      working with adult African-American patients on HD could work on developing
      targeted nutritional interventions to maintain higher SAs and BMIs while awaiting
      the results of further research in this area.

PMID- 25761049
TI  - Postoperative pancreatic fistula successfully treated with "PEG-Like" endoscopic
      vacuum therapy.
AB  - INTRODUCTION: One of the latest methods for management of pancreaticogastrostomy
      (PG) leakage after pancreaticoduodenectomy (PD) is endoscopic vacuum therapy.
      SUBJECTS AND METHODS: PD was performed on a 72-year-old man suffering from a
      nonfunctioning pancreatic neuroendocrine tumor of the head of the pancreas. On
      postoperative Day 6 after the primary surgery, postoperative pancreatic fistula
      (POPF) of the PG was revealed. Based on the International Study Group of
      Pancreatic Fistula recommendations, total parenteral nutrition, a regimen of
      somatostatin analogs, and intravenous antibiotics were implemented. The patient
      was qualified for a re-exploration because of the doubtful safety of percutaneous
      drainage of fluid collection detected in the ultrasonography scan. However, this
      management was not efficient. Endoscopic vacuum treatment (E-VAC) was initiated.
      The E-VAC was placed directly into the POPF site using a modified "percutaneous
      endoscopic gastrostomy (PEG)-like" technique. RESULTS: Over the next few days,
      the E-VAC was started. The volume of fluid collection from percutaneous drainage
      rapidly decreased, whereas the volume of E-VAC the following day after vacuum
      therapy was approximately 1000 mL. There were no signs of leakage of PG confirmed
      with endoscopy, and there was no fluid collection from peripancreatic drainage.
      The E-VAC therapy was stopped after 6 days. The patient's general condition
      improved significantly. There were no abnormalities observable in both clinical
      and imaging examinations. CONCLUSIONS: In selected patients, the "PEG-like"
      modification can be used successfully in the management of POPF. This technique
      allows the E-VAC to be placed directly in the POPF site under the endoscopic
      camera, which is what makes this method safe and efficient.

PMID- 25761050
TI  - Enantioselective fluorescent recognition in the fluorous phase: enhanced
      reactivity and expanded chiral recognition.
AB  - A novel perfluoroalkyl-BINOL-based chiral diketone is found to be the first
      highly enantioselective fluorescent sensor in the fluorous phase. One enantiomer
      of a chiral amino alcohol or diamine at a concentration greater than 1 mM can
      cause an up to 1200-2000-fold fluorescent enhancement of the sensor (0.08 mM),
      while the other enantiomer gives only a 10-50-fold enhancement. The fluorous
      phase-based sensor is found to enhance the reactivity of the previously reported
      fluorous insoluble sensor with amino alcohols and expand its chiral recognition
      ability. Dynamic light scattering studies show the formation of aggregates of
      very different particle sizes when two enantiomers of a substrate interact with
      the sensor in perfluorohexane (FC-12). This substantial difference enables easy
      discrimination of the enantiomers with UV-lamps or even the naked eye. NMR, IR,
      and mass spectroscopic studies indicate that the fluorescent enhancement and
      enantioselectivity should originate from the fluorous solvent-promoted
      nucleophilic addition of the amino alcohols to the carbonyl groups of the sensor.

PMID- 25761051
TI  - Confinement in thickness-controlled GaAs polytype nanodots.
AB  - Polytype nanodots are arguably the simplest nanodots than can be made, but their
      technological control was, up to now, challenging. We have developed a technique
      to produce nanowires containing exactly one polytype nanodot in GaAs with
      thickness control. These nanodots have been investigated by photoluminescence,
      which has been cross-correlated with transmission electron microscopy. We find
      that short (4-20 nm) zincblende GaAs segments/dots in wurtzite GaAs confine
      electrons and that the inverse system confines holes. By varying the thickness of
      the nanodots we find strong quantum confinement effects which allows us to
      extract the effective mass of the carriers. The holes at the top of the valence
      band have an effective mass of approximately 0.45 m0 in wurtzite GaAs. The
      thinnest wurtzite nanodot corresponds to a twin plane in zincblende GaAs and
      gives efficient photoluminescence. It binds an exciton with a binding energy of
      roughly 50 meV, including central cell corrections. 

PMID- 25761052
TI  - Fifteen novel EIF2B1-5 mutations identified in Chinese children with
      leukoencephalopathy with vanishing white matter and a long term follow-up.
AB  - Leukoencephalopathy with vanishing white matter (VWM) is one of the most
      prevalent inherited childhood white matter disorders, which caused by mutations
      in each of the five subunits of eukaryotic translation initiation factor 2B
      (EIF2B1-5). In our study, 34 out of the 36 clinically diagnosed children (94%)
      were identified to have EIF2B1-5 mutations by sequencing. 15 novel mutations were
      identified. CNVs were not detected in patients with only one mutant allele and
      mutation-negative determined by gene sequencing. There is a significantly higher
      incidence of patients with EIF2B3 mutations compared with Caucasian patients (32%
      vs. 4%). c.1037T>C (p.Ile346Thr) in EIF2B3 was confirmed to be a founder mutation
      in Chinese, which probably one of the causes of the genotypic differences between
      ethnicities. Our average 4.4 years-follow-up on infantile, early childhood and
      juvenile VWM children suggested a rapid deterioration in motor function. Episodic
      aggravation was presented in 90% of infantile cases and 71.4% of childhood cases.
      10 patients died during the follow-up. The Kaplan-Meier curve showed that the
      median survival time is 8.83 +/- 1.51 years. This is the largest sample of
      children in a VWM follow-up study, which is helpful for a more depth
      understanding about the natural course. 

PMID- 25761054
TI  - Culicoides monitoring in Belgium in 2011: analysis of spatiotemporal abundance,
      species diversity and Schmallenberg virus detection.
AB  - In 2011, Culicoides (Diptera: Ceratopogonidae) were collected at 16 locations
      covering four regions of Belgium with Onderstepoort Veterinary Institute (OVI)
      traps and at two locations with Rothamsted suction traps (RSTs). Quantification
      of the collections and morphological identification showed important variations
      in abundance and species diversity between individual collection sites, even for
      sites located in the same region. However, consistently higher numbers of
      Culicoides midges were collected at some sites compared with others. When species
      abundance and diversity were analysed at regional level, between-site variation
      disappeared. Overall, species belonging to the subgenus Avaritia together with
      Culicoides pulicaris (subgenus Culicoides) were the most abundant, accounting for
      80% and 96% of all midges collected with RSTs and OVI traps, respectively.
      Culicoides were present during most of the year, with Culicoides obsoletus
      complex midges found from 9 February until 27 December. Real-time reverse
      transcription polymerase chain reaction screening for Schmallenberg virus in the
      heads of collected midges resulted in the first detection of the virus in August
      2011 and identified C. obsoletus complex, Culicoides chiopterus and Culicoides
      dewulfi midges as putative vector species. At Libramont in the south of Belgium,
      no positive pools were identified. 

PMID- 25761053
TI  - Protective effects of astaxanthin on ConA-induced autoimmune hepatitis by the
      JNK/p-JNK pathway-mediated inhibition of autophagy and apoptosis.
AB  - OBJECTIVE: Astaxanthin, a potent antioxidant, exhibits a wide range of biological
      activities, including antioxidant, atherosclerosis and antitumor activities.
      However, its effect on concanavalin A (ConA)-induced autoimmune hepatitis remains
      unclear. The aim of this study was to investigate the protective effects of
      astaxanthin on ConA-induced hepatitis in mice, and to elucidate the mechanisms of
      regulation. MATERIALS AND METHODS: Autoimmune hepatitis was induced in in Balb/C
      mice using ConA (25 mg/kg), and astaxanthin was orally administered daily at two
      doses (20 mg/kg and 40 mg/kg) for 14 days before ConA injection. Levels of serum
      liver enzymes and the histopathology of inflammatory cytokines and other maker
      proteins were determined at three time points (2, 8 and 24 h). Primary
      hepatocytes were pretreated with astaxanthin (80 MUM) in vitro 24 h before
      stimulation with TNF-alpha (10 ng/ml). The apoptosis rate and related protein
      expression were determined 24 h after the administration of TNF-alpha. RESULTS:
      Astaxanthin attenuated serum liver enzymes and pathological damage by reducing
      the release of inflammatory factors. It performed anti-apoptotic effects via the
      descending phosphorylation of Bcl-2 through the down-regulation of the JNK/p-JNK
      pathway. CONCLUSION: This research firstly expounded that astaxanthin reduced
      immune liver injury in ConA-induced autoimmune hepatitis. The mode of action
      appears to be downregulation of JNK/p-JNK-mediated apoptosis and autophagy.

PMID- 25761056
TI  - Stable isotope signatures of seasonal precipitation on the Pacific coast of
      central Panama.
AB  - As calculated from data archived in the IAEA-WMO Global Network of Isotopes in
      Precipitation programme, the amount-weighted local meteoric water line for the
      Pacific coast of central Panama is: delta(2)H = 7.63(+/-0.08) * delta(18)O +
      6.51(+/-0.49). Amount-weighted mean isotopic values were regressed against the
      sea surface temperature (SST) fields of the adjacent tropical oceans. A negative
      correlation of precipitation isotope composition with Caribbean SSTs is observed
      only for the early wet season (May-June), whilst the mid-summer dry period is
      characterized by positive correlation with eastern Pacific SSTs, similar to the
      late wet season (October-November). The negative response of May-June rainfall
      isotopic composition to Caribbean SSTs is explained by a SST-mediated change in
      stratiform rain fraction from organized convective systems proximal to the Inter
      Tropical Convergence Zone (ITCZ). The positive correlation for the rest of the
      wet season, when the organized convective zone of ITCZ and its attached
      stratiform belt are distant from the Pacific coast of Panama, is interpreted as
      simple evaporative temperature effect on isotopic fractionation.

PMID- 25761055
TI  - Increased expression of interleukin-6 predicts poor response to chemoradiotherapy
      and unfavorable prognosis in oral squamous cell carcinoma.
AB  - Recent studies have revealed that cancer cells are exacerbated by chronic
      inflammation. The present study examined the immunohistochemical expression for
      interleukin-6 (IL-6), a pleiotropic inflammatory cytokine, in oral squamous cell
      carcinoma (OSCC) to elucidate the association of IL-6 expression with tumor
      progression, chemoresistance and prognosis. Seventy-eight patients with primary
      OSCC were analyzed by immunohistochemical staining for IL-6. These labeling
      indexes (LIs) were calculated and evaluated in association with the
      clinicopathologic characteristics and prognosis in the OSCC patients. The
      patients were divided into three groups as follows: negative group = LI <5%; low
      IL-6 group = 5% <= LI <30%; high IL-6 group = LI >=30%. The patient numbers of
      the negative, low and high expression groups were 24, 22 and 32, respectively. In
      the high IL-6 expression group, IL-6 receptor (IL-6R), phosphor-signal tranducer
      and activator of transcription 3 (p-STAT3) were also detected in almost all the
      cancer cells. The prevalence of the cervical lymph node or the distant metastasis
      in the high expression group was significantly higher than those in the negative
      and low expression groups. Furthermore, the high expression group had a
      significantly poorer tumor response to the preoperative chemoradiotherapy and a
      more unfavourable prognosis than the negative and the low expression groups.
      Interestingly, IL-6, IL-6R and p-STAT3 were expressed in the residual cancer
      cells of all the patients in the high expression group with poor response to
      chemoradiotherapy. These results suggested that IL-6 signaling possibly is
      involved in the progression and treatment-resistance of OSCC and IL-6 expression
      in cancer cells could be a useful predictive factor of poor response to
      chemoradiotherapy and unfavorable prognosis.

PMID- 25761057
TI  - Maternal obesity affects fetal myocardial function as early as in the first
      trimester.
AB  - OBJECTIVE: To investigate cardiac function from 14 weeks' gestation in fetuses of
      obese pregnant women (FOW). Animal studies have shown that maternal obesity
      induces fibrosis in fetal myocardium. We hypothesized that fetal cardiac function
      would be impaired among FOW. METHODS: A case-control study with longitudinal
      follow-up was performed at Trondheim University Hospital, Norway. In total, 80
      pregnant women were included and the final population comprised 52 obese and 24
      of normal weight (mean body mass index before pregnancy, 34.8 +/- 4.1 vs 21.0 +/-
      2.2 kg/m(2) ; P < 0.001). The main outcome measures were global strain rate (GSR)
      and strain by tissue Doppler imaging, tissue Doppler velocities (TDVs) and
      interventricular septal thickness assessed by fetal echocardiography at
      gestational ages of 14, 20 and 32 weeks. RESULTS: In FOW, fetal left ventricle
      (LV) and right ventricle (RV) GSR and strain were significantly lower than in
      fetuses of normal-weight pregnant women: LV GSR was 33.3% lower at 14 weeks,
      22.4% lower at 20 weeks and 22.8% lower at 32 weeks of gestation (P < 0.001) with
      no difference in fetal heart rate. Systolic and late diastolic TDVs for LV were
      significantly lower from 20 weeks' gestation and remained lower throughout
      pregnancy. Fetal interventricular septum was 26.6% (P < 0.001) thicker in late
      pregnancy in FOW compared with normal-weight pregnancies. CONCLUSIONS: At 14
      weeks of gestation, we detected fetal myocardial dysfunction with reduced LV and
      RV GSR and strain in FOW compared with fetuses of women with normal weight. Our
      finding is alarming considering the high prevalence of obesity and may partly
      explain the predisposition of offspring to cardiovascular disease later in life.

PMID- 25761058
TI  - Stereoselective Peterson olefinations from bench-stable reagents and N-phenyl
      imines.
AB  - The synthesis of bench-stable alpha,alpha-bis(trimethylsilyl)toluenes and
      tris(trimethylsilyl)methane is described and their use in stereoselective
      Peterson olefinations has been achieved with a wide substrate scope. Product
      stereoselectivity was poor with carbonyl electrophiles (E/Z ~1:1 to 4:1) though
      this was significantly improved by employing the corresponding substituted N
      benzylideneaniline (up to 99:1) as an alternative electrophile. The olefination
      byproduct was identified as N,N-bis(trimethylsilyl)aniline and could be easily
      separated from product by aqueous acid extraction. Evidence for an autocatalytic
      cycle has been obtained. 

PMID- 25761060
TI  - Isolation of phages for phage therapy: a comparison of spot tests and efficiency
      of plating analyses for determination of host range and efficacy.
AB  - Phage therapy, treating bacterial infections with bacteriophages, could be a
      future alternative to antibiotic treatment of bacterial infections. There are,
      however, several problems to be solved, mainly associated to the biology of
      phages, the interaction between phages and their bacterial hosts, but also to the
      vast variation of pathogenic bacteria which implies that large numbers of
      different phages are going to be needed. All of these phages must under present
      regulation of medical products undergo extensive clinical testing before they can
      be applied. It will consequently be of great economic importance that effective
      and versatile phages are selected and collected into phage libraries, i.e., the
      selection must be carried out in a way that it results in highly virulent phages
      with broad host ranges. We have isolated phages using the Escherichia coli
      reference (ECOR) collection and compared two methods, spot testing and efficiency
      of plating (EOP), which are frequently used to identify phages suitable for phage
      therapy. The analyses of the differences between the two methods show that spot
      tests often overestimate both the overall virulence and the host range and that
      the results are not correlated to the results of EOP assays. The conclusion is
      that single dilution spot tests cannot be used for identification and selection
      of phages to a phage library and should be replaced by EOP assays. The difference
      between the two methods can be caused by many factors. We have analysed if the
      differences and lack of correlation could be caused by lysis from without,
      bacteriocins in the phage lysate, or by the presence of prophages harbouring
      genes coding for phage resistance systems in the genomes of the bacteria in the
      ECOR collection. 

PMID- 25761059
TI  - Combined EEG/MEG can outperform single modality EEG or MEG source reconstruction
      in presurgical epilepsy diagnosis.
AB  - We investigated two important means for improving source reconstruction in
      presurgical epilepsy diagnosis. The first investigation is about the optimal
      choice of the number of epileptic spikes in averaging to (1) sufficiently reduce
      the noise bias for an accurate determination of the center of gravity of the
      epileptic activity and (2) still get an estimation of the extent of the
      irritative zone. The second study focuses on the differences in single modality
      EEG (80-electrodes) or MEG (275-gradiometers) and especially on the benefits of
      combined EEG/MEG (EMEG) source analysis. Both investigations were validated with
      simultaneous stereo-EEG (sEEG) (167-contacts) and low-density EEG (ldEEG) (21
      electrodes). To account for the different sensitivity profiles of EEG and MEG, we
      constructed a six-compartment finite element head model with anisotropic white
      matter conductivity, and calibrated the skull conductivity via somatosensory
      evoked responses. Our results show that, unlike single modality EEG or MEG,
      combined EMEG uses the complementary information of both modalities and thereby
      allows accurate source reconstructions also at early instants in time (epileptic
      spike onset), i.e., time points with low SNR, which are not yet subject to
      propagation and thus supposed to be closer to the origin of the epileptic
      activity. EMEG is furthermore able to reveal the propagation pathway at later
      time points in agreement with sEEG, while EEG or MEG alone reconstructed only
      parts of it. Subaveraging provides important and accurate information about both
      the center of gravity and the extent of the epileptogenic tissue that neither
      single nor grand-averaged spike localizations can supply. 

PMID- 25761061
TI  - NLRP3 mediates NF-kappaB activation and cytokine induction in microbially induced
      and sterile inflammation.
AB  - Nucleotide-binding domain and leucine-rich repeat-containing family, pyrin domain
      containing 3 (NLRP3) has recently emerged as a central regulator of innate
      immunity and inflammation in response to both sterile inflammatory and microbial
      invasion signals. Although its ability to drive proteolytic procaspase-1
      processing has drawn more attention, NLPR3 can also activate NF-kappaB. To
      clarify the physiological relevance of this latter function, we examined the
      effect of NLRP3 on NF-kappaB activation and cytokine induction in RNA
      interference-based NLRP3-knockdown cell lines generated from the human monocytic
      cell line THP-1. Knocking down NLRP3 reduced NF-kappaB activation and cytokine
      induction in the early stages of Staphylococcus aureus infection. Expression of
      cytokine genes induced by Staphylococcus aureus was not inhibited by a caspase-1
      inhibitor, and did not occur through an autocrine mechanism in response to newly
      synthesized cytokines. We also demonstrated that NLRP3 could activate NF-kappaB
      and induce cytokines in response to sterile signals, monosodium urate crystals
      and aluminum adjuvant. Thus, NLRP3 mediates NF-kappaB activation in both sterile
      and microbially induced inflammation. Our findings show that not only does NLRP3
      activate caspase-1 post-translationally, but it also induces multiple cytokine
      genes in the innate immune system. 

PMID- 25761063
TI  - Structural, magnetic, and redox diversity of first-row transition metal complexes
      of a pyridine-based macrocycle: well-marked trends supported by theoretical DFT
      calculations.
AB  - A series of first-row transition metal complexes with 15-membered pyridine-based
      macrocycle (3,12,18-triaza-6,9-dioxabicyclo[12.3.1]octadeca-1(18),14,16-triene =
      L) was prepared ([M(II)(L)Cl2], where M = Mn, Co, Ni, Zn (1, 3, 4, 6);
      [Fe(III)(L)Cl2]Cl (2), [Cu(II)(L)Cl]Cl (5)) and thoroughly characterized.
      Depending on the complexated metal atom, the coordination number varies from 7
      (Mn, Fe, Co), through 5 + 2 for Ni and 4 + 1 for Cu, to 5 for Zn accompanied by
      changes in the coordination geometry from the pentagonal bipyramid (1-4) to the
      square pyramid (5 and 6). Along the series, the metal-oxygen distances were
      prolonged in such manner that their bonding character was investigated, apart
      from X-ray structural analysis, also by ab initio calculations (Mayer's bond
      order, electron localization function), which confirmed that, in 4 and 5, two and
      one oxygen donor atoms are semicoordinated, respectively, and one and two oxygen
      atoms are uncoordinated in 5, and 6, respectively. On the basis of the
      temperature variable magnetic susceptibility measurements, 1 and 2 behave as
      expected for 3d(5) high-spin configuration with negligible zero-field splitting
      (ZFS). On the other hand, a large axial ZFS (D(Co) ~ 40 cm(-1), D(Ni) ~ -6.0 cm(
      1)) was found for 3 and 4, and rhombic ZFS (E/D ~ 0.15) for 4. Antiferromagnetic
      exchange coupling was observed for 4 and 5 (J(Ni) = -0.48 cm(-1), and J(Cu) = 
      2.43 cm(-1), respectively). The obtained results correlate well with ab initio
      calculations of ZFS parameters as well as J-values, which indicate that the
      antiferromagnetic exchange is mediated by hydrogen bonds. The complexes were also
      investigated by cyclic voltammetry in water or acetonitrile. A quasi-reversible
      couple Mn(II)/Mn(III) at 1.13/0.97 V, an almost reversible couple Fe(II)/Fe(III)
      at 0.51/0.25 V, and a one-step/multistep reduction/oxidation of Cu(II) complex 5
      at -0.33 V/0.06-0.61 V were detected. 

PMID- 25761064
TI  - Reactive and unreactive pathways in a photochemical ring opening reaction from 2D
      femtosecond stimulated Raman.
AB  - Two-dimensional femtosecond stimulated Raman spectroscopy (2D-FSRS) is used to
      probe the structural evolution of a modified cyclohexadiene as it undergoes a
      photoinduced ring opening reaction. Analysis of the excited state stimulated
      Raman vibrational data reveals oscillations of the center frequencies and
      amplitudes of 21 high frequency modes. These oscillations in vibrational
      properties are due to anharmonic couplings between the high frequency finger
      print modes and the impulsively driven low frequency molecular distortions in the
      excited state. The largest anharmonic couplings, with intrinsic oscillation
      magnitudes of up to 40 cm(-1), are observed between the 467 cm(-1) C-C bend and
      the 1333 cm(-1) C-C stretch with the 191 cm(-1) methyl wag, all of which are
      centered on the reactive cyclohexadiene moiety. Conversely, motions located on
      the periphery - the 993 cm(-1) phenyl bend, the 1389 cm(-1) methyl bend and 1580
      cm(-1) phenyl C-C stretch - are coupled with the 104 cm(-1) asymmetric bend.
      These couplings reveal two key energetic pathways: one leading to formation of
      the ring-opened product and the other reversion back to the ground state. This
      work is also important because it presents a new powerful method for measuring
      anharmonicities of potential energy surfaces and determining their role in
      chemical reactivity. 

PMID- 25761062
TI  - Angiopoietin-1 requires oxidant signaling through p47phox to promote endothelial
      barrier defense.
AB  - BACKGROUND: Reactive oxygen species (ROS) are largely considered to be pathogenic
      to normal endothelial function in disease states such as sepsis. We hypothesized
      that Angiopoietin-1 (Angpt-1), an endogenous agonist of the endothelial-specific
      receptor, Tie-2, promotes barrier defense by activating NADPH oxidase (NOX)
      signaling. METHODS AND FINDINGS: Using primary human microvascular endothelial
      cells (HMVECs), we found that Angpt-1 stimulation induces phosphorylation of
      p47phox and a brief oxidative burst that is lost when chemical inhibitors of NOX
      activity or siRNA against the NOX component p47phox were applied. As a result,
      there was attenuated ROS activity, disrupted junctional contacts, enhanced actin
      stress fiber accumulation, and induced gap formation between confluent HMVECs.
      All of these changes were associated with weakened barrier function. The ability
      of Angpt-1 to prevent identical changes induced by inflammatory permeability
      mediators, thrombin and lipopolysaccharides (LPS), was abrogated by p47phox
      knockdown. P47phox was required for Angpt-1 to activate Rac1 and inhibit mediator
      induced activation of the small GTPase RhoA. Finally, Angpt-1 gene transfer
      prevented vascular leakage in wildtype mice exposed to systemically administered
      LPS, but not in p47phox knock out (p47-/-) littermates. CONCLUSIONS: These
      results suggest an essential role for NOX signaling in Angpt-1-mediated
      endothelial barrier defense against mediators of systemic inflammation. More
      broadly, oxidants generated for signal transduction may have a barrier-promoting
      role in vascular endothelium.

PMID- 25761066
TI  - Peptide derived from desalinated boiled tuna extract inhibits adipogenesis
      through the downregulation of C/EBP-alpha and PPAR-gamma in 3T3-L1 adipocytes.
AB  - Recently, obesity has increased due to a variety of reasons, including the
      availability of 'fast food' and high-fat diets. Developing anti-obesity
      functional drugs and foods from natural sources may offer solutions to this
      global concern. Generally, tuna is a high-protein, low-fat and low-calorie food
      with various bioactive effects. It may improve memory, reduce cholesterol levels
      and positively affect the development of brain cells. In this study, we screened
      the anti-obesity potential of peptides derived from tuna protein. We then
      observed protein bands by the Coomassie blue staining of a sodium dodecyl sulfate
      polyacrylamide gel electrophoresis (SDS-PAGE) gel. The protein mixture was
      concentrated and desalted using in-gel trypsin digestion and a C18 nano column
      and Poros R2 reversed-phase preparation, prior to quadrupole time-of-flight mass
      spectrometry (Q-TOF MS/MS). We screened the peptides for their ability to affect
      adipogenesis in 3T3-L1 adipocytes. We also measured glucose uptake, triglyceride
      levels and lipid droplets using Oil Red O staining. As a result, we confirmed
      that one peptide inhibited adipocyte differentiation. We also observed the
      expression of obesity-related genes by western blot analysis and reverse
      transcription-polymerase chain reaction. The peptide from the tuna extract
      significantly reduced the expression levels of CCAAT/enhancer-binding protein
      alpha (C/EBP-alpha) and peroxisome proliferator-activated receptor-gamma (PPAR
      gamma) adipocyte marker genes. Thus, our data suggest that this peptide from
      boiled tuna extract reduces lipid components and adipogenesis in 3T3-L1 cells,
      and these characteristics may be of value in the development of anti-obesity
      foods.

PMID- 25761069
TI  - The next generation of cancer research and prevention.

PMID- 25761067
TI  - Early co-expression of cyclooxygenase-2 and renin in the rat kidney cortex
      contributes to the development of N(G)-nitro-L-arginine methyl ester induced
      hypertension.
AB  - We investigated the involvement of cyclooxygenase-2 (COX-2) and the renin
      angiotensin system in N(G)-nitro-L-arginine methyl ester (L-NAME)-induced
      hypertension. Male Wistar rats were treated with L-NAME (75.0 mg.(kg body mass)(
      1).day(-1), in their drinking water) for different durations (1-33 days). COX-2
      and renin mRNA were measured using real-time PCR in the renal cortex, and
      prostanoids were assessed in the renal perfusate, whereas angiotensin II (Ang II)
      and Ang (1-7) were quantified in plasma. In some rats, nitric oxide synthase
      inhibition was carried out in conjunction with oral administration of captopril
      (30.0 mg.kg(-1).day(-1)) or celecoxib (1.0 mg.kg(-1).day(-1)) for 2 or 19 days.
      We found a parallel increase in renocortical COX-2 and renin mRNA starting at day
      2 of treatment with L-NAME, and both peaked at 19-25 days. In addition, L-NAME
      increased renal 6-Keto-PGF(1alpha) (prostacyclin (PGI2) metabolite) and plasma
      Ang II from day 2, but reduced plasma Ang (1-7) at day 19. Captopril prevented
      the increase in blood pressure, which was associated with lower plasma Ang II and
      increased COX-2-derived 6-Keto-PGF(1alpha) at day 2 and plasma Ang (1-7) at day
      19. Celecoxib partially prevented the increase in blood pressure; this effect was
      associated with a reduction in plasma Ang II. These findings indicate that renal
      COX-2 expression increased in parallel with renin expression, renal PGI2
      synthesis, and plasma Ang II in L-NAME-induced hypertension.

PMID- 25761070
TI  - Good form.
AB  - New standardized prior authorization forms for health care services and
      prescription drugs released by the Texas Department of Insurance promise to
      alleviate administrative busy work and its related costs. 

PMID- 25761071
TI  - Making Over PAT.

PMID- 25761072
TI  - Caring across state lines.

PMID- 25761073
TI  - Professionalism in action.

PMID- 25761074
TI  - Grappling with small-business insurance.

PMID- 25761075
TI  - Necrotizing pancreatitis: new definitions and a new era in surgical management.
AB  - BACKGROUND: Necrotizing pancreatitis is a challenging condition that requires
      surgical treatment commonly and is associated with substantial morbidity and
      mortality. Over the past decade, new definitions have been developed for
      standardization of severity of acute and necrotizing pancreatitis, and new
      management techniques have emerged based on prospective, randomized clinical
      trials. METHODS: Review of English-language literature. RESULTS: A new
      international classification of acute pancreatitis has been developed by PANCREA
      (Pancreatitis Across Nations Clinical Research and Education Alliance) to replace
      the Atlanta Classification. It is based on the actual local (whether pancreatic
      necrosis is present or not, whether it is sterile or infected) and systemic
      determinants (whether organ failure is present or not, whether it is transient or
      persistent) of severity. Early management requires goal-directed fluid
      resuscitation (with avoidance of over-resuscitation and abdominal compartment
      syndrome), assessment of severity of pancreatitis, diagnostic computed tomography
      (CT) imaging to assess for necrotizing pancreatitis, consideration of endoscopic
      retrograde cholangiopancreatography (ERCP) for biliary pancreatitis and early
      enteral nutrition support. Antibiotic prophylaxis is not recommended. Therapeutic
      antibiotics are required for treatment of documented infected pancreatic
      necrosis. The initial treatment of infected pancreatic necrosis is percutaneous
      catheter or endoscopic (transgastric/transduodenal) drainage with a second drain
      placement as required. Lack of clinical improvement after these initial
      procedures warrants consideration of minimally invasive techniques for pancreatic
      necrosectomy including video-assisted retroperitoneal debridement (VARD),
      minimally invasive retroperitoneal pancreatectomy (MIRP), or transluminal direct
      endoscopic necrosectomy (DEN). Open necrosectomy is associated with substantial
      morbidity, but to date no randomized trial has documented superiority of either
      minimally invasive or open surgical technique. Additional trials are underway to
      address this. CONCLUSIONS: Severe acute and necrotizing pancreatitis requires a
      multi-disciplinary treatment strategy that must be individualized for each
      patient. Optimal treatment of necrotizing pancreatitis now requires a staged,
      multi-disciplinary, minimally invasive "step-up" approach that includes a team of
      interventional radiologists, therapeutic endoscopists, and surgeons.

PMID- 25761076
TI  - Skin preparation before surgery: options and evidence.
AB  - BACKGROUND: Despite many advances in surgical asepsis, surgical site infection
      (SSI) remains a challenging and costly problem. Decontamination of the skin with
      an antiseptic agent is standard practice before any trans-cutaneous invasive
      procedure, but the antiseptic agent of choice to best reduce the risk of SSI
      remains controversial. METHODS: Review of relevant literature. RESULTS: Many
      randomized controlled trials (RCTs) have evaluated chlorhexidine-based and iodine
      based preparation solutions, with and without an alcohol component. Most of these
      trials are underpowered to detect differences in SSI rates. The largest modern
      RCT showed that a chlorhexidine-isopropyl alcohol preparation reduced the risk of
      SSI substantially compared with a povidone-iodine preparation without alcohol in
      clean-contaminated surgery. Many smaller RCTs have shown that chlorhexidine
      isopropyl alcohol is superior to povidone-iodine plus isopropyl alcohol or iodine
      povacrylex plus isopropyl alcohol in pre-operative skin decontamination; whether
      or not this translates into lower SSI rates is unknown. A mixed treatment
      comparison of 10 RCTs concluded that alcohol-based preparations have a 98%
      probability of reducing the risk of SSI more effectively than aqueous-based
      preparations. Non-randomized observational studies have generally found no
      difference in SSI rates among various skin antiseptic preparations. CONCLUSIONS:
      Alcohol-based agents are likely superior to aqueous agents. Chlorhexidine may
      decrease SSI rates compared with povidone-iodine, and chlorhexidine-isopropyl
      alcohol likely offers better skin decontamination before clean surgery than
      povidone-iodine plus isopropyl alcohol or iodine povacrylex plus isopropyl
      alcohol. The quality of the available data is moderate. Rigorous, well-powered
      RCTs with appropriate treatment comparisons are needed to establish the optimal
      and most cost-effective pre-operative skin preparation in various operations and
      wound classifications.

PMID- 25761077
TI  - Divergent invariant natural killer T-cell response to sepsis of abdominal vs. non
      abdominal origin in human beings.
AB  - BACKGROUND: The etiology of sepsis is broad. The peritoneal cavity displays
      compartmentalization with respect to inflammatory responses, so peripheral blood
      responses to sepsis of abdominal vs. non-abdominal origin are expected to be
      divergent. Lymphocytes and invariant natural killer T (iNKT) cells play important
      roles in survival from sepsis, as they dampen the neutrophil and macrophage
      responses. We assessed whether circulating iNKT cells display distinct phenotypic
      profiles depending on the presence of abdominal vs. non-abdominal infection with
      sepsis. METHODS: Patients with sepsis, defined as infection confirmed
      microbiologically with a systemic inflammatory response syndrome (SIRS), were
      enrolled prospectively. They were categorized as having either exclusively sepsis
      of abdominal or exclusively non-abdominal origin. The white blood cell (WBC)
      count was recorded. Whole-blood staining with monoclonal antibodies to CD3, V
      alpha-24 (to identify iNKT cells), and CD69 (marker of early activation) was
      applied. RESULTS: Of the 53 enrolled patients, 18 had abdominal infection.
      Pneumonia was the most common non-abdominal type. There was no difference in
      gender, age, Acute Physiology and Chronic Health Evaluation (APACHE) II score,
      WBC count, or CD3(+) T cells (7.1%+/-1.6% vs. 6.5%+/-0.9%; p=0.75) in the two
      groups. Patients with abdominal infection had a higher proportion of iNKT cells
      (2.7%+/-1.1% vs. 0.89%+/-0.14%; p=0.032). Correcting for WBC count, this
      translated into a higher absolute number of iNKT cells (3.4+/-1.8*10(7)/L vs.
      0.74+/-0.15*10(7)/L; p=0.03). Patients with sepsis of abdominal origin had a
      lower percentage of CD69(+) iNKT cells (9.1%+/-3.1% vs. 27.2%+/-5.8%; p=0.028).
      In patients in shock vs. those who were not, patients with non-abdominal
      infection exhibited a greater number of iNKT cells (1.47+/-0.3 v. 0.62+/
      0.1*10(7)/L; p=0.022) and percentage of activated iNKT cells (53+/-14.5% vs.
      17.9+/-4.8%; p=0.04). Patients with non-abdominal infection who died had a lower
      absolute number of activated iNKT cells (0.8+/-1.2*10(7)/L vs. 0.34+/
      0.1*10(7)/L; p=0.023); however, no such shock or death correlation was noted in
      patients with sepsis of abdominal origin. CONCLUSIONS: Divergent sepsis
      etiologies display distinct blood iNKT cell population changes. In non-abdominal
      infection, this difference was associated with septic shock and death.
      Elucidating the importance and basis for these changes relative to the response
      to sources of infection will help clarify appropriate diagnosis and management of
      the patient with sepsis.

PMID- 25761078
TI  - External validation of the ventral hernia risk score for prediction of surgical
      site infections.
AB  - BACKGROUND: Previously, we reported that the Ventral Hernia Risk Score (VHRS) was
      more accurate in a Veterans Affairs (VA) population in predicting surgical site
      infection (SSI) after open ventral hernia repair (VHR) compared with other models
      such as the Ventral Hernia Working Group (VHWG) model. The VHRS was developed
      using single-center data and stratifies SSI risk into five groups based on
      concomitant hernia repair, skin flaps created, American Society of
      Anesthesiologists (ASA) score >=3, body mass index >=40 kg/m(2), and incision
      class 4. The purpose of this study was to validate the VHRS for other hospitals.
      METHODS: A prospective database of all open VHRs performed at three institutions
      from 2009-2011 was utilized. All 436 patients with a follow-up of at least 1 mo
      were included. The U.S. Centers for Disease Control and Prevention (CDC)
      definition of SSI was utilized. Each patient was assigned a VHRS, VHWG, and CDC
      incision classification. Receiver-operating characteristic curves were used to
      assess predictive accuracy, and the areas under the curve (AUCs) were compared
      for the three risk-stratification systems. RESULTS: The median follow-up was 20
      mos (range 1-49 mos). During this time, 111 patients (25.5%) developed a SSI. The
      AUC of the VHRS (0.73; 95% confidence interval [CI] 0.67-0.78) was greater than
      that of the VHWG (0.66; 95% CI 0.60-0.72; p<0.01) and the CDC incision class
      (0.68; 95% CI 0.61-0.74; p<0.05). CONCLUSIONS: The VHRS provides a novel,
      internally and externally validated score for a patient's likelihood of
      developing a SSI after open VHR. Elevating skin flaps, ASA score >=3, concomitant
      procedures, morbid obesity, and incision class all independently predicted SSI.
      It remains to be determined if pre-operative patient selection and risk
      reduction, surgical techniques, and post-operative management can improve
      outcomes in the highest-risk patients. The VHRS provides a starting point for key
      stakeholders to discuss the management of ventral hernias.

PMID- 25761079
TI  - Correlation between intraoperative surgical diagnosis of complicated acute
      appendicitis and the pathology report: clinical implications.
AB  - BACKGROUND: The post-operative management of appendectomy for acute appendicitis
      is based primarily on the operative findings. The surgeon describes the severity
      of the disease, and antibiotic therapy is administered accordingly. The
      histologic findings are not always considered in the decision about the
      management and may not be correlated with the clinical outcome. The aim of this
      study was to investigate the agreement between the surgeon's intra-operative
      visual description of the appendix and the pathologist's report in a consecutive
      series of patients with acute appendicitis. Complications were analyzed in
      relation to the classification. METHODS: A comparative observational study was
      performed in 69 patients who underwent surgery for acute appendicitis at the same
      hospital during a one-year period (the entire year of 2011). The surgeon's
      classification of the severity of appendicitis was compared with the
      pathologist's report using the kappa coefficient. Patient demographics, surgical
      techniques, and post-operative complications also were analyzed. RESULTS:
      Complicated appendicitis (gangrenous or perforated) was considered to be present
      in 36.2% of patients in the surgeon's classification and 43% of the patients in
      the histopathologic reports (p=0.033). The kappa coefficient showed only a weak
      correlation between the surgeons' and pathologists' descriptions (kappa=0.25).
      Significant differences in post-operative complications were found only in the
      surgeon's classification. CONCLUSION: We found a weak correlation between the
      surgeon's macroscopic diagnosis and the pathologic findings. However, the
      differences did not have meaningful clinical implications. Further studies are
      required to evaluate the clinical meaning of these results.

PMID- 25761080
TI  - Direct demonstration of bacterial biofilms on prosthetic mesh after ventral
      herniorrhaphy.
AB  - BACKGROUND: Prosthetic mesh is employed routinely in the treatment of ventral and
      parastomal hernias, but its use can lead to major complications, including
      infection, extrusion, and fistula. Bacterial biofilms have been posited to play a
      role in mesh-related infection, but although bacteria have been noted to form
      biofilms on mesh surfaces in vitro, they have never been visualized directly in
      biofilms on mesh recovered from patients experiencing infectious complications.
      METHODS: Five patients who developed complications after ventral hernia repair
      with prosthetic mesh were operated on again. Explanted mesh was examined for
      biofilm with confocal laser scanning microscopy (CLSM) and fluorescence in situ
      hybridization (FISH). In two cases, a novel molecular assay (the Ibis T5000) was
      used to characterize the biofilm-forming bacteria. RESULTS: The CLSM examination
      demonstrated adherent biofilms on mesh surfaces in all five patients. Biofilms
      also were noted on investing fibrous tissue. The FISH study was able to
      discriminate between bacterial species in polymicrobial biofilms. In two patients
      the Ibis T5000 detected more species of constituent biofilm bacteria than did
      standard culture. Removal of the mesh and reconstruction with autologous tissues
      or biologic materials resolved the presenting complaints in all cases.
      CONCLUSION: Bacterial biofilms should be considered an important contributor to
      the pathology and complications associated with prosthetic mesh implanted in the
      abdominal wall. If biofilms are present, complete removal of the mesh and repair
      of the resulting defect without alloplastic materials is an effective
      intervention.

PMID- 25761082
TI  - Molecular characterization of Staphylococcus aureus from surgical site infections
      in orthopedic patients in an orthopedic trauma clinical medical center in
      Shanghai.
AB  - BACKGROUND: Staphylococcus aureus or methicillin-resistant Staphylococcus aureus
      (MRSA) is a leading cause of surgical site infections (SSIs). The aim of our
      study was to characterize molecularly S. aureus isolates from SSIs in orthopedic
      patients in Shanghai, China. METHODS: Eighty-two S. aureus isolates (46
      methicillin-susceptible Staphylococcus aureus [MSSA] and 36 MRSA) were collected
      from SSIs in orthopedic patients. Antimicrobial susceptibility testing was
      performed according to the Clinical and Laboratory Standards Institute (CLSI)
      guidelines and a variety of clinically important toxin genes were detected. The
      sequence type, spa type, and agr group were determined to analyze the genotypes
      of all the isolates collected. In addition, MRSA isolates were characterized by
      staphylococcal cassette chromosome mec (SCCmec) type as well. RESULTS: The
      strains showed susceptibility to antibiotics such as teicoplanin, minocycline,
      quinupristin-dalfopristin, linezolid, mupirocin, and vancomycin. Ten pvl-positive
      isolates (three MRSA and seven MSSA) were found among all isolates. Eight
      community-associated MRSA (CA-MRSA) isolates were found, six of which belonged to
      ST59-MRSA-IV but most MRSA isolates (20/36, 55.6%) belonged to ST239-MRSA-III
      t030/t037 with a wide range of antibiotic resistance. By contrast, MSSA isolates
      were more diverse in both molecular characterizations and virulence factors, with
      eight MSSA isolates harboring more than six toxin genes detected. CONCLUSIONS:
      ST239-MRSA-III-t030/t037 was the epidemic clone, and healthcare-associated MRSA
      (HA-MRSA) strains might be the major pathogen causing S. aureus SSIs in
      orthopedic patients.

PMID- 25761081
TI  - Antimicrobial susceptibilities of respiratory pathogens in the surgical/trauma
      intensive care unit compared with the hospital-wide respiratory antibiogram in a
      level I trauma center.
AB  - BACKGROUND: Unit-specific antibiograms have developed to guide clinicians to
      appropriate antibiotic choices for subsets of patients. The additional level of a
      unit- and respiratory-specific antibiogram for surgical and trauma patients
      defines key differences in susceptibility information for treating hospital
      acquired pneumonia. METHODS: This was a three-year, retrospective single-center
      study. A total of 729 positive respiratory specimens from 612 patients were
      analyzed using Quality Compass Pathfinder((r)), the antibiotic-reporting
      software. Culture and susceptibility reports were compared for the
      surgical/trauma intensive care unit (S/TICU) and the general hospital (excluding
      the S/TICU but including the medical ICU [MICU]). Data were filtered to include
      those genera and organisms with a high association with hospital-acquired
      pneumonia: Acinetobacter, Citrobacter, Enterobacter, Escherichia coli,
      Haemophilus, Klebsiella, Neisseria, Pseudomonas, Staphylococcus,
      Stenotrophomonas, Streptococcus, and Serratia. RESULTS: For gram-negative
      organisms, susceptibility differences were noted for Acinetobacter and
      Pseudomonas between the S/TICU and the rest of the hospital. In particular,
      Acinetobacter was significantly more susceptible to ciprofloxacin (86% vs. 43%;
      p<0.001), gentamicin (86% vs. 54%; p=0.001), imipenem-cilastatin (93% vs. 55%;
      p<0.001), trimethoprim-sulfamethoxazole (88% vs. 54%; p=0.001), and tobramycin
      (50% vs. 0; p=0.012). Pseudomonas isolates from the S/TICU were significantly
      more susceptible to aztreonam (83% vs. 68%; p=0.037), ciprofloxacin (86% vs. 69%;
      p=0.019), and imipenem-cilastatin (94% vs. 79%; p=0.01). For gram-positive
      organisms, Staphylococcus isolates from the S/TICU were significantly more
      susceptible to erythromycin (81% vs. 57%; p=0.007) and trimethoprim
      sulfamethoxazole (98% vs. 91%; p=0.034) than were the hospital isolates.
      CONCLUSIONS: For key respiratory pathogens, such as Pseudomonas, Acinetobacter,
      and Staphylococcus, surgical and trauma patients present greater susceptibility
      to several antibiotics. Although this information cannot be extrapolated to other
      institutions, it does provide a basis for comparable institutions to consider
      developing unit- and collection-site-specific antibiograms for infections that
      affect surgical/trauma patients commonly.

PMID- 25761083
TI  - Dirofilaria (dog heartworm): a rare cause of pulmonary nodules in the United
      States.

PMID- 25761084
TI  - Peritonitis as presentation of aorto-caval fistula with Salmonella choleraesuis
      associated abdominal aortic aneurysm.
AB  - BACKGROUND: The majority of aorto-caval fistulae occur spontaneously, either as a
      result of rupture of an existing atherosclerotic abdominal aortic aneurysm into
      the vena cava or secondary to iatrogenic injuries during peripheral angiography
      or surgery. Aorto-caval fistula from an infected aortic aneurysm is a rare
      scenario, but potentially lethal. METHODS: Case report and review of the
      literature. CASE REPORT: A 63-year-old female with diabetes mellitus and liver
      cirrhosis was admitted for intractable abdominal pain with rebound tenderness. A
      computed tomography scan demonstrated an abdominal aortic aneurysm and ill
      defined peri-aortic fluid with air density and evidence of a fistula between the
      aorta and the inferior vena cava. Salmonella cholerasuis had been isolated from a
      blood culture at a previous admission. Urgent endovascular exclusion of the aorto
      caval fistula was carried out, and the infra-renal abdominal aneurysm was
      repaired using a Cook Zenith TX2 aortic stent graft. She received parenteral
      ceftriaxone for four weeks. CONCLUSIONS: This case shows acceptable short-term
      results after endovascular repair of a Salmonella-infected aorto-caval fistula.

PMID- 25761085
TI  - Aortic graft infection caused by invasive pulmonary aspergillosis.

PMID- 25761086
TI  - Trajectories of distress, anxiety, and depression among women with breast cancer:
      Looking beyond the mean.
AB  - OBJECTIVE: Little is known about the development of psychological wellbeing over
      time among women who have been treated for breast cancer. The aim of this study
      was to identify distinct patterns of distress, anxiety, and depression in such
      women. METHODS: We invited 426 consecutive women with newly diagnosed primary
      breast cancer to participate in this study, and 323 (76%) provided information on
      distress ('distress thermometer') and on symptoms of anxiety and depression
      ('hospital anxiety and depression scale'). Semiparametric group-based mixture
      modeling was used to identify distinct trajectories of distress, anxiety, and
      depressive symptoms assessed the week before surgery and four and eight months
      later. Logistic regression analysis was used to evaluate the characteristics of
      women in the distinct groups. RESULTS: Although no sub-group of women with
      chronic severe anxiety or depressive symptoms was found, we did identify a sub
      group of 8% of the women who experienced continuously severe distress. Young age,
      having a partner, shorter education, and receiving chemotherapy but not
      radiotherapy might characterize women whose psychological symptoms remain strong
      eight months after diagnosis. CONCLUSION: By looking beyond the mean, we found
      that 8% of the women experienced chronic severe distress; no sub-groups with
      chronic severe anxiety or depression were identified. Several socio-demographic
      and treatment factors characterized the women whose distress level remained
      severe eight months after diagnosis. The results suggest that support could be
      focused on relatively small groups of patients most in need.

PMID- 25761087
TI  - Influence of metabolic indicators, smoking, alcohol and socioeconomic position on
      mortality after breast cancer.
AB  - BACKGROUND: Factors differently distributed among social groups like obesity,
      metabolic syndrome, diabetes, smoking, and alcohol intake predict survival after
      breast cancer diagnosis and therefore might mediate part of the observed social
      inequality in survival. MATERIAL AND METHODS: We conducted a cohort study among
      1250 postmenopausal breast cancer patients identified among 29 875 women in the
      Danish Diet, Cancer and Health Study. Participants completed questionnaires and
      anthropometric measurements were made at enrollment. Information on survival,
      socioeconomic position, and comorbidity was obtained by linkage to national
      Danish registries. Clinical information was obtained from the nationwide Danish
      Breast Cancer Database. Selected information was obtained from hospital records
      at time of diagnosis. All analyses were based on Cox proportional hazard models,
      using death from all causes as outcome. RESULTS: Median follow-up was 9.6 years
      [interquartile range (IQR), 2.2-17.0 years]. The hazard ratio (HR) for death from
      all causes increased with lower education (p for trend, 0.01). Adjustment for
      disease-related prognostic factors, comorbidity and metabolic indicators measured
      as BMI, waist circumference and diabetes, and smoking and alcohol affected but
      did not explain the social gradient. CONCLUSION: The findings indicate that these
      factors explain some but not all the social inequality in survival after breast
      cancer and that improvement of lifestyle to some extent would improve survival
      among women with low socioeconomic position.

PMID- 25761088
TI  - The impact of co-morbidity on health-related quality of life in breast cancer
      survivors and controls.
AB  - BACKGROUND: The objective of this study was: 1) to compare health-related quality
      of life (HRQoL) scores of breast cancer survivors to matched controls; and 2) to
      examine the relative impact (explained variance) of the type and number of co
      morbidities on HRQoL. MATERIAL AND METHODS: Data from the KARMA project was used
      in this cross-sectional study. For each woman diagnosed with breast cancer (n =
      2552) there were two healthy age- and geographically matched females (n = 5104).
      Breast cancer survivors were categorized according to time since diagnosis:
      recently diagnosed (0-1 year), short- (2-5 years), mid- (6-10 years), and long
      term survivors (> 10 years). Women completed a questionnaire addressing
      demographics (age, educational level, and geographical location), lifestyle
      factors (body mass index (BMI) and smoking), co-morbidities, and HRQoL. The
      difference in explained variance in six HRQoL-domains between demographics,
      lifestyle factors, and co-morbidity in women with breast cancer and matched
      controls was examined by hierarchical regression analyses. RESULTS AND
      CONCLUSION: Women recently diagnosed (n = 63), reported the worst HRQoL followed
      by short-term survivors (2-5 years, n = 863). Thereafter, HRQoL scores further
      improved (6-10 years, n = 726), and were comparable to healthy females after 10
      years (n = 893). Co-morbidity has a negative impact on HRQoL, which increased
      with time after diagnosis. Cardiovascular disease and depression were the
      strongest associates. Breast cancer survivors report clinically significant
      improvement in HRQoL scores six years after diagnosis. Co-morbidity has a
      negative impact on HRQoL, which increases with time after diagnosis, even though
      the number of co-morbidities remains stable. In long-term survivors there should
      be increasing awareness of co-morbidity and its impact on HRQoL.

PMID- 25761089
TI  - The role of social position in anxiety and depressive symptoms among Danish
      cancer survivors.
AB  - BACKGROUND: Anxiety and depressive symptoms are common among cancer survivors.
      Studies of a possible association with social position have had divergent
      results. We examined these associations, social position being measured by
      education, in Danish cancer survivors approximately two years after diagnosis.
      MATERIAL AND METHODS: People aged over 18, living in Denmark and registered for a
      first cancer in the Danish National Patient Registry between 1 May and 31 August
      2010 were contacted; 4346 returned a questionnaire shortly after diagnosis, and
      2568 were followed up in 2012. Age, sex and cancer site were derived from the
      registry; all other information was self-reported, with that on education from
      the 2010 questionnaire and responses to the Hospital Anxiety and Depression Scale
      from the 2012 questionnaire. General linear models were used, with adjustment for
      demographic factors, cancer-specific factors, and comorbidity. RESULTS: The study
      population consisted of 1667 people (response rate, 51%). The mean symptom scores
      were 4.34 (SD 3.77) for anxiety and 2.94 (SD 3.25) for depression. People with
      medium and higher education had slightly higher anxiety symptom scores (mean
      differencemedium = 0.41, 95% CI 20.07; 0.88, mean differencehigher = 0.19, 95% CI
      20.27; 0.65). Depressive symptom scores were slightly elevated for people with
      medium education and reduced for those with higher education (mean
      differencemedium = 0.34, 95% CI 20.07; 0.75, mean differencehigher = 20,11, 95%
      CI 20.50; 0.29). Female sex, smoking-related cancers and chemotherapy were
      significantly associated with higher scores for both anxiety and depressive
      symptoms, but somatic comorbidity and mental disorders at the time of treatment
      were most strongly, significantly associated with elevated anxiety and depressive
      symptom scores. CONCLUSION: No overall significant differences in anxiety or
      depressive symptom scores were found with length of education. Previous mental
      disorders and somatic comorbidity are the strongest indicators of higher levels
      of anxiety and depressive symptoms.

PMID- 25761090
TI  - Reduced vaginal elasticity, reduced lubrication, and deep and superficial
      dyspareunia in irradiated gynecological cancer survivors.
AB  - PURPOSE: The purpose of this study was to examine whether or not vaginal
      elasticity or lack of lubrication is associated with deep or superficial
      dyspareunia. We investigated gynecological cancer survivors treated with
      radiation therapy. METHODS: In a population-based study with 616 women answering
      a questionnaire (participation rate 78%) and who were treated with radiotherapy
      for gynecological cancer, we analyzed information from 243 women (39%) who
      reported that they had had intercourse during the previous six months. Analyses
      included log-binomial regression (relative risks) and multiple imputations by
      chained equations in combination with Bayesian Model Averaging, yielding a
      posterior probability value. Age range of this cancer recurrent-free group of
      women was 29-80. RESULTS: Dyspareunia affected 164 of 243 of the women (67%). One
      hundred thirty-four women (55%) reported superficial pain, 97 women (40%)
      reported deep pain, and 87 women (36%) reported both types of dyspareunia. The
      relative risk (RR) of deep dyspareunia was 1.87 (CI 1.41-2.49) with impaired
      vaginal elasticity compared to normal vaginal elasticity. Age and lower abdominal
      swelling were separate risk factors for deep dyspareunia. However, effects remain
      after adjusting for these factors. CONCLUSION: The relative risk of deep
      dyspareunia was almost twice as high with impaired vaginal elasticity compared to
      normal vaginal elasticity. If we wish to treat or even prevent deep dyspareunia
      in women with gynecological cancer, we may use our knowledge of the
      pathophysiology of deep dyspareunia and increasingly provide dilators together
      with instructions on how to use them for stretching exercises in order to retain
      vaginal elasticity. Results highlight the need for studies with more precise
      questions distinguishing superficial from deep dyspareunia so that in the future
      we may be able to primarily try to avoid reduced vaginal elasticity and
      secondarily reduce the symptoms.

PMID- 25761091
TI  - Social position and referral to rehabilitation among cancer patients.
AB  - OBJECTIVES: In Denmark, most healthcare services, including cancer treatment and
      rehabilitation, are offered free of charge by referral from a treating physician;
      thus, social equality should be expected. In a population-based cohort study of
      registry-based data, we examined the association between socioeconomic position,
      measured as educational level, and referral to rehabilitation services among
      cancer patients. MATERIAL AND METHODS: Through the Danish Cancer Registry, we
      identified all people resident in the Municipality of Copenhagen with cancer
      diagnosed in 2007-2012. Information on all rehabilitation referrals was retrieved
      from the Municipal Centre for Cancer Rehabilitation for 2009-2012. Information on
      demographic and socioeconomic characteristics was obtained from national Danish
      registers. The Cox proportional hazards model was used to investigate
      associations between educational level and referral to rehabilitation with
      adjustment for sex, age, diagnosis, disposable income, cohabitation status and
      number of children living at home at the time of diagnosis. RESULTS: A primary
      cancer was diagnosed in 13 840 people, of whom 2148 (16%) were referred to
      rehabilitation services during follow-up. In the fully adjusted model, we found
      education to be a predictor of referral, with a hazard ratio of 1.33 (95% CI 1.19
      1.49) for patients with long education and a hazard ratio of 1.15 (95% CI 1.03
      1.29) for patients with medium education as compared with patients with short
      education. CONCLUSIONS: Our findings suggest that, even after differences in
      demographics and cancer characteristics are accounted for, referral to
      rehabilitation services is not equally distributed by social group. Higher
      educational level is associated with a higher probability of referral to
      rehabilitation services.

PMID- 25761092
TI  - Constant pattern of relapse in primary central nervous lymphoma patients treated
      with high-dose methotrexate combinations. A Finnish retrospective study.
AB  - BACKGROUND: Primary central nervous system lymphoma (PCNSL) is a rare brain
      tumour with a dismal prognosis. Several phase II studies with high-dose
      methotrexate-based regimens have shown promising early results, but in all
      hospital-based data published so far, the disease outcome is poor. MATERIAL AND
      METHODS: We performed a hospital-based retrospective analysis to evaluate the
      long-term results of the Nordic type of Bonn chemotherapy regimen in PCNSL
      patients. The study included 54 patients with newly diagnosed PCNSL who received
      chemotherapy with curative intent as their first-line treatment. RESULTS: We
      found promising response rates, 76% of the patients achieving CR and 22% patients
      achieving PR, with corresponding two-year EFS 53% and OS 76%. However, with
      longer follow-up a constant pattern of relapses was observed with only one
      patient remaining in primary remission after 60 months. DISCUSSION: The finding
      suggests that basic biological differences exist between PCNSL and systemic
      diffuse large B-cell lymphoma and there is a need for consolidation or
      maintenance therapy after achieving a remission in patients with PCNSL.

PMID- 25761093
TI  - Optimized patient-trajectory for patients undergoing treatment with high-dose
      chemotherapy and autologous stem cell transplantation.
AB  - PURPOSE: Before, during and after autologous hematopoietic stem cell
      transplantation (HD-ASCT) patients suffer from significant loss of physical
      function, and experience multiple complications during and after hospitalization.
      Studies regarding safety and feasibility of physical exercise interventions for
      patients undergoing treatment with HD-ASCT are missing. METHODS: Forty patients
      referred to HD-ASCT treatment, suffering from multiple myeloma, lymphoma or
      amyloidosis aged 23-70 years were enrolled in a prospective longitudinal study.
      The study consisted of a home-based exercise program for use in the ambulatory
      setting and supervised exercise sessions Monday to Friday for 30-40 minutes
      during admission. Safety of the exercise program and physical tests were assessed
      by using a weekly questionnaire and report of inadvertent incidences. Adherence
      to the home-based exercise program was reported by using a patient diary, weekly
      questionnaire and count of daily attendance in supervised sessions during
      hospital stay. Data collection was scheduled shortly after diagnosis, admission,
      discharge and eight weeks after discharge. Success criteria were: no severe
      adverse events in relation to exercise program and assessments; performance of
      three days of physical exercises during ambulatory period and hospital stay and
      150 minutes of weekly physical activity. RESULTS: Of the 25 patients who
      completed the exercise program during the ambulatory period prior to HD-ASCT a
      mean weekly attendance to home exercises of 5.3 (+/- 2.8) days and a median
      weekly physical activity of 240 (+/- 153.8) minutes was found. During hospital
      stay the median attendance was 9 (+/- 3.9) days of 10 (+/- 6.9) possible. Two
      months after discharge the patients reported a median weekly physical activity of
      360 (2745.5) minutes. No severe adverse events in relation to the exercise
      program or assessments were reported. CONCLUSION: Based on the enrolled number of
      patients the physical exercise intervention for patients undergoing HD-ASCT seems
      promising regarding feasibility and safety.

PMID- 25761094
TI  - Synthesis of polysaccharide-block-polypeptide copolymer for potential co-delivery
      of drug and plasmid DNA.
AB  - A pH-sensitive, biodegradable, and biocompatible polysaccharide-block-polypeptide
      Copolymer derivative {Ac-Dex-b-PAsp(DET)} is synthetized from acetal-modified
      dextran (Ac-Dex) and diethylenetriamine (DET) grafted poly(L-aspartic acid)
      {PAsp(DET)} by using click and aminolysis reaction. The copolymer can self
      assemble into cationic nanopaticles for potential co-delivery of plasmid DNA
      (pEGFP-N3) and anticancer drug (doxorubicin, DOX), by using water/oil/water
      (w/o/w) emulsion method. Gel retardation assay reveals that pDNA can be
      effectively complexed into cationic nanoparticles at N/P ratio = 12. In vitro
      drug release behavior of DOX-NPs and DOX/pDNA-NPs is achieved by using
      fluorescence spectra and UV-Vis spectra and confocal laser scanning microscopy
      (CLSM). And, pEGFP-N3-NPs at N/P ratio = 42 presents the considerable potential
      in cell transfection. Cell viability assay shows that nanoparticles exhibit low
      cell cytotoxicity. These results suggest that the copolymer has excellent
      performance and potential for the co-delivery of gene and drugs.

PMID- 25761095
TI  - In Vivo Dark-Field Radiography for Early Diagnosis and Staging of Pulmonary
      Emphysema.
AB  - OBJECTIVES: The aim of this study was to evaluate the suitability of in vivo x
      ray dark-field radiography for early-stage diagnosis of pulmonary emphysema in
      mice. Furthermore, we aimed to analyze how the dark-field signal correlates with
      morphological changes of lung architecture at distinct stages of emphysema.
      MATERIALS AND METHODS: Female 8- to 10-week-old C57Bl/6N mice were used
      throughout all experiments. Pulmonary emphysema was induced by orotracheal
      injection of porcine pancreatic elastase (80-U/kg body weight) (n = 30). Control
      mice (n = 11) received orotracheal injection of phosphate-buffered saline. To
      monitor the temporal patterns of emphysema development over time, the mice were
      imaged 7, 14, or 21 days after the application of elastase or phosphate-buffered
      saline. X-ray transmission and dark-field images were acquired with a prototype
      grating-based small-animal scanner. In vivo pulmonary function tests were
      performed before killing the animals. In addition, lungs were obtained for
      detailed histopathological analysis, including mean cord length (MCL)
      quantification as a parameter for the assessment of emphysema. Three blinded
      readers, all of them experienced radiologists and familiar with dark-field
      imaging, were asked to grade the severity of emphysema for both dark-field and
      transmission images. RESULTS: Histopathology and MCL quantification confirmed the
      introduction of different stages of emphysema, which could be clearly visualized
      and differentiated on the dark-field radiograms, whereas early stages were not
      detected on transmission images. The correlation between MCL and dark-field
      signal intensities (r = 0.85) was significantly higher than the correlation
      between MCL and transmission signal intensities (r = 0.37). The readers' visual
      ratings for dark-field images correlated significantly better with MCL (r = 0.85)
      than visual ratings for transmission images (r = 0.36). Interreader agreement and
      the diagnostic accuracy of both quantitative and visual assessment were
      significantly higher for dark-field imaging than those for conventional
      transmission images. CONCLUSIONS: X-ray dark-field radiography can reliably
      visualize different stages of emphysema in vivo and demonstrates significantly
      higher diagnostic accuracy for early stages of emphysema than conventional
      attenuation-based radiography.

PMID- 25761096
TI  - Niraparib: A Poly(ADP-ribose) Polymerase (PARP) Inhibitor for the Treatment of
      Tumors with Defective Homologous Recombination.
AB  - Poly(ADP-ribose) polymerases (PARPs) are involved in DNA repair following damage
      by endogenous or exogenous processes. It has become clear over the past decade
      that inhibition of PARP in the context of defects in other DNA repair mechanisms
      provide a tumor specific way to kill cancer cells. We describe the rationale for
      this approach and the design and discovery of niraparib, a potent PARP-1/2
      inhibitor with good cell based activity, selectivity for cancer over normal
      cells, and oral bioavailability. Niraparib was characterized in a number of
      preclinical models before moving to phase I clinical trials, where it showed
      excellent human pharmacokinetics suitable for once a day oral dosing, achieved
      its pharmacodynamic target for PARP inhibition, and had promising activity in
      cancer patients. It is currently being tested in phase 3 clinical trials as
      maintenance therapy in ovarian cancer and as a treatment for breast cancer. 

PMID- 25761097
TI  - A neural mechanism for time-window separation resolves ambiguity of adaptive
      coding.
AB  - The senses of animals are confronted with changing environments and different
      contexts. Neural adaptation is one important tool to adjust sensitivity to
      varying intensity ranges. For instance, in a quiet night outdoors, our hearing is
      more sensitive than when we are confronted with the plurality of sounds in a
      large city during the day. However, adaptation also removes available information
      on absolute sound levels and may thus cause ambiguity. Experimental data on the
      trade-off between benefits and loss through adaptation is scarce and very few
      mechanisms have been proposed to resolve it. We present an example where
      adaptation is beneficial for one task--namely, the reliable encoding of the
      pattern of an acoustic signal-but detrimental for another--the localization of
      the same acoustic stimulus. With a combination of neurophysiological data,
      modeling, and behavioral tests, we show that adaptation in the periphery of the
      auditory pathway of grasshoppers enables intensity-invariant coding of amplitude
      modulations, but at the same time, degrades information available for sound
      localization. We demonstrate how focusing the response of localization neurons to
      the onset of relevant signals separates processing of localization and pattern
      information temporally. In this way, the ambiguity of adaptive coding can be
      circumvented and both absolute and relative levels can be processed using the
      same set of peripheral neurons.

PMID- 25761098
TI  - Structure-guided insights on the role of NS1 in flavivirus infection.
AB  - We highlight the various domains of the flavivirus virulence factor NS1 and
      speculate on potential implications of the NS1 3D structure in understanding its
      role in flavivirus pathogenesis. Flavivirus non-structural protein 1 (NS1) is a
      virulence factor with dual functions in genome replication and immune evasion.
      Crystal structures of NS1, combined with reconstructions from electron microscopy
      (EM), provide insight into the architecture of dimeric NS1 on cell membranes and
      the assembly of a secreted hexameric NS1-lipid complex found in patient sera.
      Three structural domains of NS1 likely have distinct roles in membrane
      association, replication complex assembly, and immune system avoidance. A
      conserved hydrophobic inner face is sequestered either on the membrane or in the
      interior of the secreted hexamer and contains regions implicated in viral
      replication. The exposed variable outer face is presented to cellular and
      secreted components of the immune system in infected patients and contains
      candidate regions for immune system modulation. We anticipate that knowledge of
      the distinct NS1 domains and assembly will lead to advances in elucidating virus
      host interactions mediated through NS1 and in dissecting the role of NS1 in viral
      genome replication. 

PMID- 25761099
TI  - An efficient polymeric micromotor doped with Pt nanoparticle@carbon nanotubes for
      complex bio-media.
AB  - A highly efficient polymeric tubular micromotor doped with Pt nanoparticle@carbon
      nanotubes is fabricated by template-assisted electrochemical growth. The
      micromotors preserve good navigation in multi-media and surface modification,
      along with simple synthesis, easy functionalization and good biocompatibility,
      displaying great promise in biological applications. 

PMID- 25761100
TI  - Beta-blockers use for hypertension in the elderly.
AB  - Beta-blockers are considered as suitable drugs to treat essential hypertension
      also in elderly patients and they are currently recommended for treatment of
      hypertension, even in older patients, by the ESH/ESC Guidelines. Different meta
      analyses and results of some large clinical trials have shown that here is no
      clinically difference between beta-blockers and other drug classes in decreasing
      high blood pressure in elderly hypertensive patients. The new vasodilating beta
      blockers, as nebivolol, carvedilol and celiprolol, offer additional important
      advantages, compared with traditional beta-blockers. The cardio-protective effect
      of beta-blockers (except atenolol) is not inferior to that obtained with other
      drug classes which is independent of age and gender of the patients. 

PMID- 25761101
TI  - Hypertension in the elderly.
AB  - Data collected over a 30-year period have demonstrated the increasing prevalence
      of hypertension with age. Aging is an inevitable part of life and brings along
      two inconvenient events: physiologic decline and disease state. High blood
      pressure (HBP) is an important risk factor for cardiovascular morbidity and
      mortality, particularly in the elderly. It is a significant and often
      asymptomatic chronic disease, which requires optimal control and persistent
      adherence to prescribed medication to reduce the risks of cardiovascular,
      cerebrovascular and renal disease. Hypertension in the elderly patients
      represents a management dilemma to geriatric and cardiovascular specialists and
      other practitioners. Furthermore, with the wide adoption of multiple drug
      strategies targeting subgroups of hypertensive patients with specific risk
      conditions to lower blood pressure (BP), difficult questions arise about how
      aggressive treatment of elderly patients should be. The purpose of the following
      chapter article is to review the pathophysiology of aging as well as the
      epidemiology and the clinical assessment of high blood pressure (HBP) in older
      people. 

PMID- 25761102
TI  - Calcium channel blockers in the management of hypertension in the elderly.
AB  - The aging population is rapidly increasing, and is mainly due to medical advances
      and the control of chronic diseases, with a real worldwide increase in the
      elderly population. Special emphasis has been placed on the management of
      hypertension in the geriatric patient, since its long-term benefits have been
      shown to prevent both cerebral and cardiac infarctions. Calcium channel blockers
      have been shown to be effective in this condition in the elderly. Their success
      depends on their mechanism of action, as well as on the physiological changes
      observed, and on the aging process itself, which include cardiac hypertrophy,
      calcification of cardiac valves, and a decrease in the excitation-conduction
      system. There is thickening of the tunica intima of the arteries, and the
      production of nitric oxide at cellular level decreases with age, along with an
      increase in endothelin 1, which leads to vascular endothelium dysfunction. In the
      kidneys, there is a decrease in prostacyclin, endothelial hyperpolarization
      factor, as well as the Klotho anti-aging protein, which leads to an increase in
      blood pressure. Calcium channel blocker drugs have been shown to be effective in
      any age group for the management of hypertension, and are safe in the elderly
      patients. These drugs block L-type calcium channels, with the long-acting or
      latest generation dihydropyridines being the most effective of this group.
      Several studies, including SYST-EUR2, NORDIL, and STOP-2, have demonstrated the
      effectiveness of these drugs in the geriatric patient. The prescribing of long
      acting calcium channel blocker drugs in a single dose is the most recommended.
      The safety in the use of this drug group has been demonstrated in the treatment
      of hypertension in the elderly patient, with a level of effectiveness similar to
      other widely used drugs. 

PMID- 25761103
TI  - Diuretics in the treatment of elderly hypertensive patients.
AB  - Systolic arterial hypertension is the most common variable of the hypertensive
      disease and it is mainly concentrated in individuals who are 60 years old and
      older. At a global level, such population is rapidly growing in every society. In
      senior persons, losing weight and lowering sodium consumption helps decreasing
      Blood pressure (BP). Using antihypertensive medications reduces cardiovascular
      mortality. In this chapter the management of BP with diuretics is discussed. 

PMID- 25761104
TI  - Resistant hypertension in the elderly-second line treatments: aldosterone
      antagonists, central alpha-agonist agents, alpha-adrenergic receptor blockers,
      direct vasodilators, and exogenous nitric oxide donors.
AB  - Resistant hypertension (RH) is a prevalent medical problem across all ages but is
      more frequent in elderly patients. This entity has to be distinguished from
      clinical settings which may simulate it such as apparent hypertension
      (pseudohypertension) or apparently resistant hypertension (pseudoresistant
      hypertension) [1]. An appropriate therapy for RH can be achieved by the addition
      of second line antihypertensive drugs: antialdosteronic diuretics, central
      agents, alpha blockers, direct vasodilating agents, and exogenous nitric oxide
      donors. These antihypertensive drugs are considered as second line drugs since
      they are less effective as monotherapy to reduce blood pressure (they induce
      counte regulatory responses that limit their antihypertensive effect such as
      volume expansion or reflex tachycardia) and prevent cardiovascular events, or due
      to significant adverse effects (postural hypotension, sedation, hyperkalemia).
      Second line drugs are also used when there is allergy or intolerance to the first
      line ones [2, 3]. 

PMID- 25761105
TI  - Lifestyle changes and surgical treatment for hypertension in the elderly.
AB  - Hypertension is a major cardiovascular risk factor that increases morbidity and
      mortality in the elderly because, numerous factors contribute to development and
      progression of hypertension in elderly patients, including excessive salt
      intakes, obesity, physical inactivity and stress. Hypertension treatment usually
      results in a combination of both, pharmacologic and non-pharmacologic measures.
      These latter are an essential part of treatment and cannot be replaced by the
      medication. Non pharmacologic management known as lifestyle modifications has a
      pivotal role in non-hypertensive and hypertensive individuals. In case of non
      hypertensive or pre-hypertensive patients it can prevent hypertension development
      and in hypertensive people it has the capacity to lower blood pressure levels as
      well as modify cardiovascular complications. Older people tend more often to
      treatment resistance so it is increasingly necessary to have other therapeutic
      resources for patients with difficult control of disease. Minimally invasive
      techniques are developing that might improve the course of the disease and
      prevent its complications by a more extended time.In this chapter, we will review
      components of nonpharmacological treatment of hypertension focusing on the
      geriatric patient. 

PMID- 25761106
TI  - Recommendations for the treatment of hypertension in elderly people.
AB  - High blood pressure is a major cardiovascular risk factor. The prevalence of
      hypertension increases with aging. As a consequence of changes in arterial wall
      that leads to arterial stiffness, the majority of elderly patients suffer
      isolated systolic hypertension. The evidence strongly supports that hypertension
      in the elderly is associated with an increase in stroke risk and cardiovascular
      mortality and morbidity. Several trials have shown the benefits of treating
      hypertension in elderly patients. Even in the very old patients, the use of
      antihypertensive agents such as calcium channel blockers, thiazide and thiazide
      like diuretics, and inhibitors of the renin-angiotensin system reduce the risk of
      complications in those patients. However, most patients will need two or more
      drugs to reach the recommended goals. Hypertension in the elderly has special
      conditions that must be assessed in the evaluation of the patient (as
      pseudohypertension and white coat hypertension), and issues that may affect the
      therapeutic choice and the response to treatment, as comorbidities and
      polypharmacy. 

PMID- 25761107
TI  - Evaluating the consent preferences of UK research volunteers for genetic and
      clinical studies.
AB  - OBJECTIVES: To establish the views of research volunteers on the consent process;
      to explore their views on the consent process in different research scenarios; to
      inform debate on emerging models of consent for participation in research.
      DESIGN, SETTING AND PARTICIPANTS: 2,308 adult volunteers from the TwinsUK
      Registry (www.twinsuk.ac.uk) completed an online survey about their views on the
      consent process for use of their DNA and medical information in research. Their
      views on the re-consenting process in different scenarios were assessed. RESULTS:
      The majority of volunteers preferred to be informed of the identity of the main
      researcher of a study in which they are participating, which is contrary to
      current practice. Over 80% were willing to complete the consent process online
      instead of face to face. On the whole, respondents did not view their DNA
      differently from their medical information with regard to the consent process.
      Research participants were more willing to give broad consent to cover future
      research if their DNA was to be used by the original researcher than by another
      researcher, even if the disease under investigation varied, in contrast to the
      traditional 'gold standard' whereby specific consent is required for all new
      research projects. DISCUSSION: In some scenarios, research participants reported
      that they would be comfortable with not signing a new consent form for future
      research uses of their data and DNA, and are comfortable with secure, online
      consent processes rather than traditional face-to-face consent processes. Our
      findings indicate that the perceived relationship between research participants
      and researchers plays an important role in shaping preferences regarding the
      consent process and suggest that this relationship is not captured by traditional
      consent processes. We argue that the development of new formats of consent should
      be informed by empirical research on volunteers' perceptions and preferences
      regarding the consent process.

PMID- 25761108
TI  - Application of a combined three-stage system for reclamation of tunnel
      construction wastewater.
AB  - A combined three-stage system, (1) coagulation (2) zeocarbon filtration and (3)
      membrane filtration, a combination of microfiltration (MF) and reverse osmosis
      (RO), was investigated for reclamation of tunnel construction wastewater having a
      salinity of 10.8-12.90/00 and a concentration of suspended solids (SS) in the
      range of 264-1084 mg/L. The initial stages - coagulation, zeocarbon filtration
      and MF - served as a precursor to RO membrane filtration to successfully reduce
      water contaminants to less than 0.2 nephelometric turbidity units (NTU) of
      turbidity, thereby minimizing the potential for fouling. The RO system
      subsequently removed over 99% of remaining pollutants including ionic substances,
      resulting in less than 0.02 NTU turbidity, less than 0.04 mg/L total nitrogen
      (TN) and less than 0.01 mg/L total phosphorus (TP). Also, addition of an RO
      system markedly reduced high salt concentrations (high chloride (Cl(-))
      concentrations) in the wastewater, exceeding 99% salt elimination. Thus,
      reclaimed water from our combined system met and exceeded currently regulatory
      quality standards for wastewater reuse (turbidity <= 2.0 NTU; TN <= 10 mg/L; TP
      <= 0.5 mg/L; Cl(-) <= 250 mg/L).

PMID- 25761109
TI  - Phase II DeCOG-study of ipilimumab in pretreated and treatment-naive patients
      with metastatic uveal melanoma.
AB  - PURPOSE: Up to 50% of patients with uveal melanoma (UM) develop metastatic
      disease with limited treatment options. The immunomodulating agent ipilimumab has
      shown an overall survival (OS) benefit in patients with cutaneous metastatic
      melanoma in two phase III trials. As patients with UM were excluded in these
      studies, the Dermatologic Cooperative Oncology Group (DeCOG) conducted a phase II
      to assess the efficacy and safety of ipilimumab in patients with metastatic UM.
      PATIENTS AND METHODS: We undertook a multicenter phase II study in patients with
      different subtypes of metastatic melanoma. Here we present data on patients with
      metastatic UM (pretreated and treatment-naive) who received up to four cycles of
      ipilimumab administered at a dose of 3 mg/kg in 3 week intervals. Tumor
      assessments were conducted at baseline, weeks 12, 24, 36 and 48 according to
      RECIST 1.1 criteria. Adverse events (AEs), including immune-related AEs were
      graded according to National Cancer Institute Common Toxicity Criteria (CTC)
      v.4.0. Primary endpoint was the OS rate at 12 months. RESULTS: Forty five
      pretreated (85%) and eight treatment-naive (15%) patients received at least one
      dose of ipilimumab. 1-year and 2-year OS rates were 22% and 7%, respectively.
      Median OS was 6.8 months (95% CI 3.7-8.1), median progression-free survival 2.8
      months (95% CI 2.5-2.9). The disease control rate at weeks 12 and 24 was 47% and
      21%, respectively. Sixteen patients had stable disease (47%), none experienced
      partial or complete response. Treatment-related AEs were observed in 35 patients
      (66%), including 19 grade 3-4 events (36%). One drug-related death due to
      pancytopenia was observed. CONCLUSIONS: Ipilimumab has very limited clinical
      activity in patients with metastatic UM. Toxicity was manageable when treated as
      per protocol-specific guidelines. TRIAL REGISTRATION: ClinicalTrials.gov
      NCT01355120.

PMID- 25761111
TI  - Is it Oscar-worthy? Children's metarepresentational understanding of acting.
AB  - Although it is an essential aspect of one of the most common forms of
      entertainment, psychologists know almost nothing about how children understand
      the act of portraying a character in a realistic manner-realistic acting. Do
      children possess the sort of meta-theory of acting that adults possess? In two
      studies we find that, unlike adults, children between the ages of 3-5 do not
      think that a realistic actor is better at portraying a characteristic than a
      nonrealistic actor, nor do they prefer one to the other. As they develop, they
      come to understand that realistic acting is different from nonrealistic acting,
      but unlike adults, children think that a nonrealistic, pretense-like portrayal is
      more difficult to achieve than a realistic representation of an emotional or
      physical state. These findings show that children's metarepresentational
      understanding of acting is relatively immature at age 5, and that their
      understanding of this specific domain of pretense lags behind their understanding
      of pretense in general. 

PMID- 25761110
TI  - Enhanced neuronal glucose transporter expression reveals metabolic choice in a HD
      Drosophila model.
AB  - Huntington's disease is a neurodegenerative disorder caused by toxic insertions
      of polyglutamine residues in the Huntingtin protein and characterized by
      progressive deterioration of cognitive and motor functions. Altered brain glucose
      metabolism has long been suggested and a possible link has been proposed in HD.
      However, the precise function of glucose transporters was not yet determined.
      Here, we report the effects of the specifically-neuronal human glucose
      transporter expression in neurons of a Drosophila model carrying the exon 1 of
      the human huntingtin gene with 93 glutamine repeats (HQ93). We demonstrated that
      overexpression of the human glucose transporter in neurons ameliorated
      significantly the status of HD flies by increasing their lifespan, reducing their
      locomotor deficits and rescuing eye neurodegeneration. Then, we investigated
      whether increasing the major pathways of glucose catabolism, glycolysis and
      pentose-phosphate pathway (PPP) impacts HD. To mimic increased glycolytic flux,
      we overexpressed phosphofructokinase (PFK) which catalyzes an irreversible step
      in glycolysis. Overexpression of PFK did not affect HQ93 fly survival, but
      protected from photoreceptor loss. Overexpression of glucose-6-phosphate
      dehydrogenase (G6PD), the key enzyme of the PPP, extended significantly the
      lifespan of HD flies and rescued eye neurodegeneration. Since G6PD is able to
      synthesize NADPH involved in cell survival by maintenance of the redox state, we
      showed that tolerance to experimental oxidative stress was enhanced in flies co
      expressing HQ93 and G6PD. Additionally overexpressions of hGluT3, G6PD or PFK
      were able to circumvent mitochondrial deficits induced by specific silencing of
      genes necessary for mitochondrial homeostasis. Our study confirms the involvement
      of bioenergetic deficits in HD course; they can be rescued by specific expression
      of a glucose transporter in neurons. Finally, the PPP and, to a lesser extent,
      the glycolysis seem to mediate the hGluT3 protective effects, whereas, in
      addition, the PPP provides increased protection to oxidative stress. 

PMID- 25761113
TI  - Solubility of polyethers in hydrocarbons at low temperatures. A model for
      potential genetic backbones on warm titans.
AB  - Ethers are proposed here as the repeating backbone linking units in linear
      genetic biopolymers that might support Darwinian evolution in hydrocarbon oceans.
      Hydrocarbon oceans are found in our own solar system as methane mixtures on
      Titan. They may be found as mixtures of higher alkanes (propane, for example) on
      warmer hydrocarbon-rich planets in exosolar systems ("warm Titans"). We report
      studies on the solubility of several short polyethers in propane over its liquid
      range (from 85 to 231 K, or -188  degrees C to -42  degrees C). These show that
      polyethers are reasonably soluble in propane at temperatures down to ca. 200 K.
      However, their solubilities drop dramatically at still lower temperatures and
      become immeasurably low below 170 K, still well above the ~ 95 K in Titan's
      oceans. Assuming that a liquid phase is essential for any living system, and
      genetic biopolymers must dissolve in that biosolvent to support Darwinism, these
      data suggest that we must look elsewhere to identify linear biopolymers that
      might support genetics in Titan's surface oceans. However, genetic molecules with
      polyether backbones may be suitable to support life in hydrocarbon oceans on warm
      Titans, where abundant organics and environments lacking corrosive water might
      make it easier for life to originate.

PMID- 25761112
TI  - Detection of a novel, integrative aging process suggests complex physiological
      integration.
AB  - Many studies of aging examine biomarkers one at a time, but complex systems
      theory and network theory suggest that interpretations of individual markers may
      be context-dependent. Here, we attempted to detect underlying processes governing
      the levels of many biomarkers simultaneously by applying principal components
      analysis to 43 common clinical biomarkers measured longitudinally in 3694 humans
      from three longitudinal cohort studies on two continents (Women's Health and
      Aging I & II, InCHIANTI, and the Baltimore Longitudinal Study on Aging). The
      first axis was associated with anemia, inflammation, and low levels of calcium
      and albumin. The axis structure was precisely reproduced in all three populations
      and in all demographic sub-populations (by sex, race, etc.); we call the process
      represented by the axis "integrated albunemia." Integrated albunemia increases
      and accelerates with age in all populations, and predicts mortality and frailty-
      but not chronic disease--even after controlling for age. This suggests a role in
      the aging process, though causality is not yet clear. Integrated albunemia
      behaves more stably across populations than its component biomarkers, and thus
      appears to represent a higher-order physiological process emerging from the
      structure of underlying regulatory networks. If this is correct, detection of
      this process has substantial implications for physiological organization more
      generally.

PMID- 25761115
TI  - Expression of freezing and fear-potentiated startle during sustained fear in
      mice.
AB  - Fear-potentiated acoustic startle paradigms have been used to investigate phasic
      and sustained components of conditioned fear in rats and humans. This study
      describes a novel training protocol to assess phasic and sustained fear in freely
      behaving C57BL/6J mice, using freezing and/or fear-potentiated startle as
      measures of fear, thereby, if needed, allowing in vivo application of various
      techniques, such as optogenetics, electrophysiology and pharmacological
      intervention, in freely behaving animals. An auditory Pavlovian fear conditioning
      paradigm, with pseudo-randomized conditioned-unconditioned stimulus presentations
      at various durations, is combined with repetitive brief auditory white noise
      burst presentations during fear memory retrieval 24 h after fear conditioning.
      Major findings are that (1) a motion sensitive platform built on mechano
      electrical transducers enables measurement of startle responses in freely
      behaving mice, (2) absence or presence of startle stimuli during retrieval as
      well as unpredictability of a given threat determine phasic and sustained fear
      response profiles and (3) both freezing and startle responses indicate phasic and
      sustained components of behavioral fear, with sustained freezing reflecting
      unpredictability of conditioned stimulus (CS)/unconditioned stimulus (US)
      pairings. This paradigm and available genetically modified mouse lines will pave
      the way for investigation of the molecular and neural mechanisms relating to the
      transition from phasic to sustained fear. 

PMID- 25761114
TI  - Shift work and the relationship with metabolic syndrome in Chinese aged workers.
AB  - BACKGROUND: Shift work is indicated to be associated with adverse metabolic
      disorders. However, potential effects of shift work on metabolic syndrome (MetS)
      and its components have not been well established. METHODS: In total, 26,382
      workers from Dongfeng-Tongji Cohort were included in this study. Information on
      shift work history was gathered through questionnaires and metabolic traits were
      measured. Logistic regression models were used to calculate the odds ratio (OR)
      and 95% confidence interval (CI) for long-term shift work related with MetS and
      each component, respectively. Further stratification analysis was performed to
      detect the differences on MetS between female and male shift workers. RESULTS:
      Long-term shift work was associated with MetS without adjusting for any
      confounders. Compared with the group of non-shift work, the multivariate-adjusted
      ORs (95%CI) of MetS associated with 1-10, 11-20, and >=20y of shift work were
      1.05 (0.95-1.16), 1.14 (1.03-1.26), 1.16 (1.01-1.31), respectively. In female
      workers, we found a dose-response relationship that every 10 years increase in
      shift work was associated with a 10% (95% CI: 1%-20%) elevated OR of MetS, while
      no significant dose-response trend was found among male workers. Furthermore,
      shift work duration was significantly associated with ORs of high blood pressure
      (1.07, 1.01-1.13), long waist circumference (1.10, 1.01-1.20) and high glucose
      levels (1.09, 1.04-1.15). No significant association was observed between shift
      work and low HDL cholesterol) and raised triglyceride levels. CONCLUSIONS: Long
      term shift work was associated with metabolic syndrome and the association might
      differ by gender in retired workers. Applicable intervention strategies are
      needed for prevention of metabolic disorders for shift workers.

PMID- 25761116
TI  - alpha-Synuclein-induced synapse damage in cultured neurons is mediated by
      cholesterol-sensitive activation of cytoplasmic phospholipase A2.
AB  - The accumulation of aggregated forms of the alpha-synuclein (alphaSN) is
      associated with the pathogenesis of Parkinson's disease (PD) and Dementia with
      Lewy Bodies. The loss of synapses is an important event in the pathogenesis of
      these diseases. Here we show that aggregated recombinant human alphaSN, but not
      betaSN, triggered synapse damage in cultured neurons as measured by the loss of
      synaptic proteins. Pre-treatment with the selective cytoplasmic phospholipase A2
      (cPLA2) inhibitors AACOCF3 and MAFP protected neurons against alphaSN-induced
      synapse damage. Synapse damage was associated with the alphaSN-induced activation
      of synaptic cPLA2 and the production of prostaglandin E2. The activation of cPLA2
      is the first step in the generation of platelet-activating factor (PAF) and PAF
      receptor antagonists (ginkgolide B or Hexa-PAF) also protect neurons against
      alphaSN-induced synapse damage. alphaSN-induced synapse damage was also reduced
      in neurons pre-treated with the cholesterol synthesis inhibitor (squalestatin).
      These results are consistent with the hypothesis that alphaSN triggered synapse
      damage via hyperactivation of cPLA2. They also indicate that alphaSN-induced
      activation of cPLA2 is influenced by the cholesterol content of membranes.
      Inhibitors of this pathway that can cross the blood brain barrier may protect
      against the synapse damage seen during PD. 

PMID- 25761118
TI  - Thermodynamics calculation of protein-ligand interactions by QM/MM polarizable
      charge parameters.
AB  - The calculation of protein-ligand binding free energy (DeltaG) is of great
      importance for virtual screening and drug design. Molecular dynamics (MD)
      simulation has been an attractive tool to investigate this scientific problem.
      However, the reliability of such approach is affected by many factors including
      electrostatic interaction calculation. Here, we present a practical protocol
      using quantum mechanics/molecular mechanics (QM/MM) calculations to generate
      polarizable QM protein charge (QMPC). The calculated QMPC of some atoms in
      binding pockets was obviously different from that calculated by AMBER ff03, which
      might significantly affect the calculated DeltaG. To evaluate the effect, the MD
      simulations and MM/GBSA calculation with QMPC for 10 protein-ligand complexes,
      and the simulation results were then compared to those with the AMBER ff03 force
      field and experimental results. The correlation coefficient between the
      calculated DeltaDeltaG using MM/GBSA under QMPC and the experimental data is .92,
      while that with AMBER ff03 force field is .47 for the complexes formed by
      streptavidin or its mutants and biotin. Moreover, the calculated DeltaDeltaG with
      QMPC for the complexes formed by ERbeta and five ligands is positively related to
      experimental result with correlation coefficient of .61, while that with AMBER
      ff03 charge is negatively related to experimental data with correlation
      coefficient of .42. The detailed analysis shows that the electrostatic
      polarization introduced by QMPC affects the electrostatic contribution to the
      binding affinity and thus, leads to better correlation with experimental data.
      Therefore, this approach should be useful to virtual screening and drug design. 

PMID- 25761119
TI  - Identical assemblage of Giardia duodenalis in humans, animals and vegetables in
      an urban area in southern Brazil indicates a relationship among them.
AB  - BACKGROUND: Giardia duodenalis infects humans and other mammals by ingestion of
      cysts in contaminated water or food, or directly in environments with poor
      hygiene. Eight assemblages, designated A-H, are described for this species.
      METHODOLOGY/PRINCIPAL FINDINGS: We investigated by microscopy or by direct
      immunofluorescence technique the occurrence of G. duodenalis in 380 humans, 34
      animals, 44 samples of water and 11 of vegetables. G. duodenalis cysts present in
      samples were genotyped through PCR-RFLP of beta giardin and glutamate
      dehydrogenase (gdh) genes and sequencing of gdh. The gdh gene was amplified in
      76.5% (26/34) of the human faeces samples with positive microscopy and in 2.9%
      (1/34) of negative samples. In 70.4% (19/27) of the positive samples were found
      BIV assemblage. In two samples from dogs with positive microscopy and one
      negative sample, assemblages BIV, C, and D were found. Cysts of Giardia were not
      detected in water samples, but three samples used for vegetable irrigation showed
      total coliforms above the allowed limit, and Escherichia coli was observed in one
      sample. G. duodenalis BIV was detected in two samples of Lactuca sativa irrigated
      with this sample of water. BIV was a common genotype, with 100% similarity,
      between different sources or hosts (humans, animals and vegetables), and the one
      most often found in humans. CONCLUSIONS/SIGNIFICANCE: This is the first study in
      Brazil that reports the connection among humans, dogs and vegetables in the
      transmission dynamics of G. duodenalis in the same geographic area finding
      identical assemblage. BIV assemblage was the most frequently observed among these
      different links in the epidemiological chain.

PMID- 25761120
TI  - A genetic predisposition score associates with reduced aerobic capacity in
      response to acute normobaric hypoxia in lowlanders.
AB  - Given the high inter-individual variability in the sensitivity to high altitude,
      we hypothesize the presence of underlying genetic factors. The aim of this study
      was to construct a genetic predisposition score based on previously identified
      high-altitude gene variants to explain the inter-individual variation in the
      reduced maximal O2 uptake (DeltaVo2max) in response to acute hypoxia. Ninety-six
      healthy young male Belgian lowlanders were included. In both normobaric normoxia
      (Fio2=20.9%) and acute normobaric hypoxia (Fio2=10.7%-12.5%) Vo2max was measured.
      Forty-one SNPs in 21 genes were genotyped. A stepwise regression analysis was
      applied to detect a subset of SNPs to be associated with DeltaVo2max. This subset
      of SNPs was included in the genetic predisposition score. A general linear model
      and regression analysis with age, weight, height, hypoxic protocol group, and
      Vo2max in normoxia as covariates were used to test the explained variance of the
      genetic predisposition score. A ROC analysis was performed to discriminate
      between the low- and high DeltaVo2max subgroups. A stepwise regression analysis
      revealed a subset of SNPs [rs833070 (VEGFA), rs4253778 (PPARA), rs6735530
      (EPAS1), rs4341 (ACE), rs1042713 (ADRB2), and rs1042714 (ADRB2)] to be associated
      with DeltaVo2max. The genetic predisposition score was found to be an independent
      predictive variable with a partial explained variance of 23% (p<0.0001). A ROC
      analysis showed significant discriminating accuracy (AUC=0.78, 95% confidence
      interval=0.64-0.91) between the low- and high DeltaVo2max subgroups. This six-SNP
      based genetic predisposition score showed a significantly predictive value for
      DeltaVo2max.

PMID- 25761122
TI  - Adsorption and desorption of U(VI) on functionalized graphene oxides: a combined
      experimental and theoretical study.
AB  - The adsorption and desorption of U(VI) on graphene oxides (GOs), carboxylated GOs
      (HOOC-GOs), and reduced GOs (rGOs) were investigated by batch experiments, EXAFS
      technique, and computational theoretical calculations. Isothermal adsorptions
      showed that the adsorption capacities of U(VI) were GOs > HOOC-GOs > rGOs,
      whereas the desorbed amounts of U(VI) were rGOs > GOs > HOOC-GOs by desorption
      kinetics. According to EXAFS analysis, inner-sphere surface complexation
      dominated the adsorption of U(VI) on GOs and HOOC-GOs at pH 4.0, whereas outer
      sphere surface complexation of U(VI) on rGO was observed at pH 4.0, which was
      consistent with surface complexation modeling. Based on the theoretical
      calculations, the binding energy of [G(...)UO2](2+) (8.1 kcal/mol) was
      significantly lower than those of [HOOC-GOs(...)UO2](2+) (12.1 kcal/mol) and [GOs
      O(...)UO2](2+) (10.2 kcal/mol), suggesting the physisorption of UO2(2+) on rGOs.
      Such high binding energy of [GOs-COO(...)UO2](+) (50.5 kcal/mol) revealed that
      the desorption of U(VI) from the -COOH groups was much more difficult. This paper
      highlights the effect of the hydroxyl, epoxy, and carboxyl groups on the
      adsorption and desorption of U(VI), which plays an important role in designing
      GOs for the preconcentration and removal of radionuclides in environmental
      pollution cleanup applications.

PMID- 25761123
TI  - Effects of biceps tension on the torn superior glenoid labrum.
AB  - The purpose of this study was to evaluate the role of the tension on the long
      head of the biceps tendon in the propagation of SLAP tears by studying the
      mechanical behavior of the torn superior glenoid labrum. A previously validated
      finite element model was extended to include a glenoid labrum with type II SLAP
      tears of three different sizes. The strain distribution within the torn labral
      tissue with loading applied to the biceps tendon was investigated and compared to
      the inact and unloaded conditions. The anterior and posterior edges of each SLAP
      tear experienced the highest strain in the labrum. Labral strain increased with
      increasing biceps tension. This effect was stronger in the labrum when the size
      of the tear exceeded the width of the biceps anchor on the superior labrum. Thus,
      this study indicates that biceps tension influences the propagation of a SLAP
      tear more than it does the initiation of a tear. Additionally, it also suggests
      that the tear size greater than the biceps anchor site as a criterion in
      determining optimal treatment of a type II SLAP tear.

PMID- 25761124
TI  - Physiological and molecular responses in brain of juvenile common carp (Cyprinus
      carpio) following exposure to tributyltin.
AB  - Tributyltin (TBT), as antifouling paints, is widely present in aquatic
      environment, but little is known regarding the toxicity of TBT on fish brain. In
      this study, the effects of exposure to TBT on the antioxidant defense system,
      Na(+) -K(+) -ATPase activity, neurological enzymes activity and Hsp 70 protein
      level in brain of juvenile common carp (Cyprinus carpio) were studied. Fish were
      exposed to sublethal concentrations of TBT (5, 10 and 20 MUg/L) for 7 days. Based
      on the results, with increasing concentrations of TBT, oxidative stress was
      apparent as reflected by the significant higher levels of oxidative indices, as
      well as the significant inhibition of all antioxidant enzymes activities.
      Besides, the activities of Acetylcholinesterase (AChE), Monoamine oxidases (MAO)
      and Na(+) -K(+) -ATPase were significantly inhibited after exposure to TBT with
      higher concentrations. In addition, the levels of Hsp 70 protein were evaluated
      under TBT stress with dose-depended manner. These results suggest that selected
      physiological responses in fish brain could be used as potential biomarkers for
      monitoring residual organotin compounds present in aquatic environment.

PMID- 25761125
TI  - The evidence for a changing real world of real world evidence.

PMID- 25761127
TI  - Energy and charge transfer in nanoscale hybrid materials.
AB  - Hybrid materials composed of colloidal semiconductor quantum dots and pi
      conjugated organic molecules and polymers have attracted continuous interest in
      recent years, because they may find applications in bio-sensing, photodetection,
      and photovoltaics. Fundamental processes occurring in these nanohybrids are light
      absorption and emission as well as energy and/or charge transfer between the
      components. For future applications it is mandatory to understand, control, and
      optimize the wide parameter space with respect to chemical assembly and the
      desired photophysical properties. Accordingly, different approaches to tackle
      this issue are described here. Simple organic dye molecules (Dye)/quantum dot
      (QD) conjugates are studied with stationary and time-resolved spectroscopy to
      address the dynamics of energy and ultra-fast charge transfer. Micellar as well
      as lamellar nanostructures derived from diblock copolymers are employed to fine
      tune the energy transfer efficiency of QD donor/dye acceptor couples. Finally,
      the transport of charges through organic components coupled to the quantum dot
      surface is discussed with an emphasis on functional devices. 

PMID- 25761128
TI  - Two new cucurbitane-type triterpenoid saponins isolated from ethyl acetate
      extract of Citrullus colocynthis fruit.
AB  - Two new cucurbitacins I (1 and 2), together with eight known compounds (3-10),
      were isolated from the ethyl acetate extract of the fruit of Citrullus
      colocynthis. Compounds 3, 5-9 were isolated from C. colocynthis for the first
      time. The structures of new compounds were determined primarily from IR, HR-MS,
      1D-, and 2D-NMR analysis. 

PMID- 25761126
TI  - Computational analysis of an autophagy/translation switch based on mutual
      inhibition of MTORC1 and ULK1.
AB  - We constructed a mechanistic, computational model for regulation of
      (macro)autophagy and protein synthesis (at the level of translation). The model
      was formulated to study the system-level consequences of interactions among the
      following proteins: two key components of MTOR complex 1 (MTORC1), namely the
      protein kinase MTOR (mechanistic target of rapamycin) and the scaffold protein
      RPTOR; the autophagy-initiating protein kinase ULK1; and the multimeric energy
      sensing AMP-activated protein kinase (AMPK). Inputs of the model include
      intrinsic AMPK kinase activity, which is taken as an adjustable surrogate
      parameter for cellular energy level or AMP:ATP ratio, and rapamycin dose, which
      controls MTORC1 activity. Outputs of the model include the phosphorylation level
      of the translational repressor EIF4EBP1, a substrate of MTORC1, and the
      phosphorylation level of AMBRA1 (activating molecule in BECN1-regulated
      autophagy), a substrate of ULK1 critical for autophagosome formation. The model
      incorporates reciprocal regulation of mTORC1 and ULK1 by AMPK, mutual inhibition
      of MTORC1 and ULK1, and ULK1-mediated negative feedback regulation of AMPK.
      Through analysis of the model, we find that these processes may be responsible,
      depending on conditions, for graded responses to stress inputs, for bistable
      switching between autophagy and protein synthesis, or relaxation oscillations,
      comprising alternating periods of autophagy and protein synthesis. A sensitivity
      analysis indicates that the prediction of oscillatory behavior is robust to
      changes of the parameter values of the model. The model provides testable
      predictions about the behavior of the AMPK-MTORC1-ULK1 network, which plays a
      central role in maintaining cellular energy and nutrient homeostasis. 

PMID- 25761129
TI  - Treatment of idiopathic oligozoospermia with recombinant human follicle
      stimulating hormone: a prospective, randomized, double-blind, placebo-controlled
      clinical study in Chinese population.
AB  - OBJECTIVE: Follicle-stimulating hormone plays a crucial role in spermatogenesis.
      The aim of this study was to evaluate the efficacy of treatment with FSH in
      Chinese infertility population. DESIGN: Prospective, randomized, double-blind,
      placebo-controlled clinical study. PATIENTS: A total of 354 men affected by
      idiopathic oligozoospermia from three medical centres. MEASUREMENTS: This study
      contained three parts: (i) treatment with different doses of rhFSH (50 IU, 100
      IU, 200 IU and 300 IU); (ii) the efficacy of rhFSH at different periods (2, 3, 4,
      5 months); (iii) FSH treatment in patients with different levels of inhibin B
      (normal-level group, low-level group and high-level group). Semen parameters were
      evaluated in all subjects. The patients who had not reached spontaneous pregnancy
      underwent assisted reproductive techniques. RESULTS: Sperm number was
      significantly increased after treatment with FSH at doses of at least 200 IU, and
      the improvement was observed beginning at the third month. The significant
      improvement in both morphology and forward motility was observed beginning at the
      fifth month. Moreover, 300 IU rhFSH administration for 5 months could
      significantly improve the spontaneous pregnancy rate (12/40) and ART pregnancy
      rate (14/28), while the rates for placebo group were two of twenty-nine and five
      of twenty-seven, respectively. The seminal parameters (total sperm count, sperm
      concentration, forward motility and morphology) were significantly improved in
      the normal- and low-level inhibin B groups, but no significant variation was
      observed in the high-level group at the end of the study. CONCLUSIONS: The
      efficacy of FSH treatment was associated with the dose of FSH and duration of
      treatment, and FSH therapy was more effective in patients with normal level and
      low level of inhibin B.

PMID- 25761130
TI  - New class of bioluminogenic probe based on bioluminescent enzyme-induced electron
      transfer: BioLeT.
AB  - Bioluminescence imaging (BLI) has advantages for investigating biological
      phenomena in deep tissues of living animals, but few design strategies are
      available for functional bioluminescent substrates. We propose a new design
      strategy (designated as bioluminescent enzyme-induced electron transfer: BioLeT)
      for luciferin-based bioluminescence probes. Luminescence measurements of a series
      of aminoluciferin derivatives confirmed that bioluminescence can be controlled by
      means of BioLeT. Based on this concept, we developed bioluminescence probes for
      nitric oxide that enabled quantitative and sensitive detection even in vivo. Our
      design strategy should be applicable to develop a wide range of practically
      useful bioluminogenic probes. 

PMID- 25761131
TI  - A Method for Making a Lymphatic Specimen of the Dorsum of the Hand.
AB  - PURPOSE: To make a lymphatic specimen of the dorsum of the hand for educational
      and clinical purposes. METHODS: A total of four hands from two unembalmed human
      cadavers were used. Under a surgical microscope, 6% hydrogen peroxide was
      employed to detect the lymphatic vessels commencing from fingers. A 30-gauge
      needle was inserted into vessels and injected with a barium sulphate mixture.
      Each specimen was radiographed, photographed, and dissected to demonstrate the
      lymphatic vessels on the dorsum of the hand. After being embalmed in 4% formalin
      for 3 months, specimen was then sealed in a plexiglass container for display.
      RESULTS: An average of sixteen lymph collecting vessels were found in the
      subcutaneous tissue of the dorsum of the hand. The diameter of the vessels varied
      from 0.2 mm to 0.6 mm. Vessels were the continuation of lymph vessels arising
      from fingers. They travelled meanderingly in the subcutaneous tissue and
      traversed over or under the veins when they met. CONCLUSION: Actual and accurate
      lymphatic distributions of the dorsum of the hand have been described and
      displayed. The information upgrades our anatomical knowledge and the results will
      be of benefit for the lymphatic education and clinical application.

PMID- 25761132
TI  - The professional socialization of the graduate assistant athletic trainer.
AB  - CONTEXT: The graduate assistant athletic trainer (AT) position often serves as
      one's first experience working independently as an AT and is also an important
      aspect of the professional socialization process. The socialization experiences
      of graduate assistant ATs have yet to be fully explored. OBJECTIVE: To understand
      the socialization process for graduate assistant ATs during their graduate
      experience. DESIGN: Qualitative study. SETTING: We conducted phone interviews
      with all participants. PATIENTS OR OTHER PARTICIPANTS: A total of 25 graduate
      assistant ATs (20 women, 5 men) studying in 1 of 3 academic tracks: (1)
      accredited postprofessional athletic training program (n = 8), (2)
      postprofessional athletic training program (n = 11), or (3) a nonathletic
      training degree program (n = 6). The average age was 25 +/- 5 years, and the
      median age was 24 years. Participants were certified by the Board of
      Certification for an average of 2 +/- 0.4 years. DATA COLLECTION AND ANALYSIS: We
      analyzed the data using a general inductive approach. Peer review, field notes,
      and intercoder reliability established trustworthiness. Data saturation guided
      participant recruitment. RESULTS: The ability to gain clinical independence as a
      practitioner was an important socialization process. Having the chance to develop
      a relationship with a mentor, who provided support, guidance, and more of a
      hierarchical relationship, was an important socializing agent for the graduate
      assistant AT. Participants used the orientation session as a means to understand
      the expectations and role of the graduate-assistant position. Academic coursework
      was a way to achieve better inductance into the role via the opportunity to apply
      classroom skills during their clinical practice. CONCLUSIONS: Socializing the
      graduate assistant blends formal and informal processes. Transition to practice
      is a critical aspect of the profession; thus, supporting autonomous practice with
      directed mentoring can promote professional maturity.

PMID- 25761133
TI  - Athletic trainers' barriers to maintaining professional commitment in the
      collegiate setting.
AB  - CONTEXT: Professional commitment simply describes one's obligation to his or her
      work. For athletic trainers (ATs), the demanding work environment and job
      expectations may affect their characterization of professional commitment. Our
      breadth of knowledge regarding professional commitment within athletic training
      is narrow. OBJECTIVE: To evaluate the professional commitment of ATs in the
      collegiate setting. DESIGN: Qualitative study. SETTING: Collegiate. PATIENTS OR
      OTHER PARTICIPANTS: Thirty-three Board of Certification-certified ATs employed in
      the collegiate setting (National Collegiate Athletic Association Division I = 11,
      Division II = 9, Division III = 13) with an average of 10 +/- 8 years of clinical
      experience volunteered. Data saturation guided the total number of participants.
      DATA COLLECTION AND ANALYSIS: Online journaling via QuestionPro was completed by
      all participants. Multiple-analyst triangulation and peer review were conducted
      for data credibility. Analysis followed a general inductive method. RESULTS: Four
      themes speak to the factors that negatively affect ATs' professional enthusiasm
      and commitment: (1) life stage, (2) work overload, (3) organizational climate,
      and (4) human resources. The latter 3 speak to the effect the workplace can have
      on ATs' professional commitment, and the first speaks to the effect outside
      responsibilities can have. CONCLUSIONS: Our results suggest that several of the
      factors that negatively influence the professional commitment of collegiate ATs
      are modifiable organizational components. Developing resiliency strategies at the
      individual and organizational levels may help to facilitate improved professional
      commitment for the AT.

PMID- 25761134
TI  - Injury history, sex, and performance on the functional movement screen and Y
      balance test.
AB  - CONTEXT: Research is limited regarding the effects of injury or surgery history
      and sex on the Functional Movement Screen (FMS) and Y Balance Test (YBT).
      OBJECTIVE: To determine if injury or surgery history or sex affected results on
      the FMS and YBT. DESIGN: Cross-sectional study. SETTING: Athletic training
      facilities. PATIENTS OR OTHER PARTICIPANTS: A total of 200 National Collegiate
      Athletic Association Division I female (n = 92; age = 20.0 +/- 1.4 years, body
      mass index = 22.8 +/- 3.1 kg/m(2)) and male (n = 108; age = 20.0 +/- 1.5 years,
      body mass index = 27.0 +/- 4.6 kg/m(2)) athletes were screened; 170 completed the
      FMS, and 190 completed the YBT. INTERVENTION(S): A self-reported questionnaire
      identified injury or surgery history and sex. The FMS assessed movement during
      the patterns of deep squat, hurdle step, in-line lunge, shoulder mobility,
      impingement-clearing test, straight-leg raise, trunk stability push-up, press-up
      clearing test, rotary stability, and posterior-rocking clearing test. The YBT
      assessed balance while participants reached in anterior, posteromedial, and
      posterolateral directions. MAIN OUTCOME MEASURE(S): The FMS composite score (CS;
      range, 0-21) and movement pattern score (range, 0-3), the YBT CS (% lower
      extremity length), and YBT anterior, posteromedial, and posterolateral asymmetry
      (difference between limbs in centimeters). Independent-samples t tests
      established differences in mean FMS CS, YBT CS, and YBT asymmetry. The Mann
      Whitney U test identified differences in FMS movement patterns. RESULTS: We found
      lower overall FMS CSs for the following injuries or surgeries: hip (injured =
      12.7 +/- 3.1, uninjured = 14.4 +/- 2.3; P = .005), elbow (injured = 12.1 +/- 2.8,
      uninjured = 14.3 +/- 2.4; P = .02), and hand (injured = 12.3 +/- 2.9, uninjured =
      14.3 +/- 2.3; P = .006) injuries and shoulder surgery (surgery = 12.0 +/- 1.0, no
      surgery = 14.3 +/- 2.4; P < .001). We observed worse FMS movement pattern
      performance for knee surgery (rotary stability: P = .03), hip injury (deep squat
      and hurdle: P < .042 for both), hip surgery (hurdle and lunge: P < .01 for both),
      shoulder injury (shoulder and hand injury: P < .02 for both), and shoulder
      surgery (shoulder: P < .02). We found better FMS movement pattern performance for
      trunk/back injury (deep squat: P = .02) and ankle injury (lunge: P = .01). Female
      athletes performed worse in FMS movement patterns for trunk (P < .001) and rotary
      (P = .01) stability but better in the lunge (P = .008), shoulder mobility (P <
      .001), and straight-leg raise (P < .001). Anterior asymmetry was greater for male
      athletes (P = .02). CONCLUSIONS: Injury history and sex affected FMS and YBT
      performance. Researchers should consider adjusting for confounders.

PMID- 25761135
TI  - Athletic trainers' facilitators of professional commitment in the collegiate
      setting.
AB  - CONTEXT: Professional responsibility, rewards and respect, and time for
      rejuvenation are factors supporting professional commitment for athletic trainers
      (ATs) in the high school setting. The inherent complexities of an occupational
      setting can mitigate perceptions of professional commitment. Thus far, evidence
      is lacking regarding professional commitment for ATs in other occupational
      settings. OBJECTIVE: To extend the literature on professional commitment of the
      AT to the collegiate setting. DESIGN: Qualitative study. SETTING: Collegiate.
      PATIENTS OR OTHER PARTICIPANTS: Thirty-three Board of Certification-certified ATs
      employed in the collegiate setting (National Collegiate Athletic Association
      Division I = 11, Division II = 9, Division III = 13) with an average of 10 +/- 8
      years of clinical experience volunteered. Data saturation guided the total number
      of participants. DATA COLLECTION AND ANALYSIS: Online journaling via QuestionPro
      was used to collect data from all participants. Two strategies, multiple-analyst
      triangulation and peer review, were completed to satisfy data credibility. Data
      were evaluated using a general inductive approach. RESULTS: Likert-scale data
      revealed no differences regarding levels of professional commitment across
      divisions. Two themes emerged from the inductive-content analysis: (1)
      professional responsibility and (2) coworker support. The emergent theme of
      professional responsibility contained 4 subthemes: (1) dedication to advancing
      the athletic training profession, (2) ardor for job responsibilities, (3)
      dedication to the student-athlete, and (4) commitment to education. Our
      participants were able to better maintain their own professional commitment when
      they felt their coworkers were also committed to the profession. CONCLUSIONS: The
      collegiate ATs investigated in this study, regardless of division, demonstrated
      professional commitment propelled by their aspiration to advance the profession,
      as well as their dedication to student-athletes and athletic training students.
      Maintaining commitment was influenced by a strong sense of coworker support.

PMID- 25761137
TI  - Correction: Dynamic grouping of hippocampal neural activity during cognitive
      control of two spatial frames.

PMID- 25761136
TI  - Skin Cooling and Force Replication at the Ankle in Healthy Individuals: A
      Crossover Randomized Controlled Trial.
AB  - CONTEXT: Proprioception of the ankle is determined by the ability to perceive the
      sense of position of the ankle structures, as well as the speed and direction of
      movement. Few researchers have investigated proprioception by force-replication
      ability and particularly after skin cooling. OBJECTIVE: To analyze the ability of
      the ankle-dorsiflexor muscles to replicate isometric force after a period of skin
      cooling. DESIGN: Randomized controlled clinical trial. SETTING: Laboratory.
      PATIENTS OR OTHER PARTICIPANTS: Twenty healthy individuals (10 men, 10 women; age
      = 26.8 +/- 5.2 years, height = 171 +/- 7 cm, mass = 66.8 +/- 10.5 kg).
      INTERVENTION(S): Skin cooling was carried out using 2 ice applications: (1) after
      maximal voluntary isometric contraction (MVIC) performance and before data
      collection for the first target force, maintained for 20 minutes; and (2) before
      data collection for the second target force, maintained for 10 minutes. We
      measured skin temperature before and after ice applications to ensure skin
      cooling. MAIN OUTCOME MEASURE(S): A load cell was placed under an inclined board
      for data collection, and 10 attempts of force replication were carried out for 2
      values of MVIC (20%, 50%) in each condition (ice, no ice). We assessed force
      sense with absolute and root mean square errors (the difference between the force
      developed by the dorsiflexors and the target force measured with the raw data and
      after root mean square analysis, respectively) and variable error (the variance
      around the mean absolute error score). A repeated-measures multivariate analysis
      of variance was used for statistical analysis. RESULTS: The absolute error was
      greater for the ice than for the no-ice condition (F1,19 = 9.05, P = .007) and
      for the target force at 50% of MVIC than at 20% of MVIC (F1,19 = 26.01, P <
      .001). CONCLUSIONS: The error was greater in the ice condition and at 50% of
      MVIC. Skin cooling reduced the proprioceptive ability of the ankle-dorsiflexor
      muscles to replicate isometric force.

PMID- 25761139
TI  - "Onset of Depression Inventory"--comparison between the data of depressed
      patients and their relatives.
AB  - BACKGROUND: The "Onset of Depression Inventory" (ODI) represents a patient
      interview which aims to register the speed of onset of depression systematically.
      The purpose of this study was to evaluate the patient-relative agreement
      regarding the speed of onset of depression in the patients. METHODS: The ODI was
      investigated in 31 patients with a depressive episode. Moreover, 31 patients'
      relatives participated in an interview for which a modified version of the ODI
      (for relatives of depressed patients; ODI-A) was applied. RESULTS: There was a
      significant association between patients' estimation of the speed of onset of the
      depressive episode and relatives' estimation of this parameter in the case of
      patients and relatives living in a common household (rho = 0.68; p = 0.006).
      CONCLUSIONS: There was an agreement between patients and their relatives
      regarding the speed of onset of the current depressive episodes, however only if
      they lived in a common household.

PMID- 25761138
TI  - Should the WHO growth charts be used in France?
AB  - BACKGROUND: Growth charts are an essential clinical tool for evaluating a child's
      health and development. The current French reference curves, published in 1979,
      have recently been challenged by the 2006 World Health Organization (WHO) growth
      charts. OBJECTIVE: To evaluate and compare the growth of French children who were
      born between 1981 and 2007, with the WHO growth charts and the French reference
      curves currently used. DESIGN: Anthropometric measurements from French children,
      who participated in 12 studies, were analyzed: 82,151 measurements were available
      for 27,257 children in different age groups, from birth to 18 years. We
      calculated and graphically compared mean z-scores based on the WHO and French
      curves, for height, weight and Body Mass Index (BMI) according to age and sex.
      The prevalence of overweight using the WHO, the French and International Obesity
      Task Force definitions were compared. RESULTS: Our population of children was on
      average 0.5 standard deviations taller than the French reference population, from
      the first month of life until puberty age. Mean z-scores for height, weight and
      BMI were closer to zero based on the WHO growth charts than on the French
      references from infancy until late adolescence, except during the first six
      months. These differences not related to breastfeeding rates. As expected, the
      prevalence of overweight depended on the reference used, and differences varied
      according to age. CONCLUSION: The WHO growth charts may be appropriate for
      monitoring growth of French children, as the growth patterns in our large
      population of French children were closer to the WHO growth charts than to the
      French reference curves, from 6 months onwards. However, there were some
      limitations in the use of these WHO growth charts, and further investigation is
      needed.

PMID- 25761141
TI  - Revealing energy level structure of individual quantum dots by tunneling rate
      measured by single-electron sensitive electrostatic force spectroscopy.
AB  - We present theoretical and experimental studies of the effect of the density of
      states of a quantum dot (QD) on the rate of single-electron tunneling that can be
      directly measured by electrostatic force microscopy (e-EFM) experiments. In e
      EFM, the motion of a biased atomic force microscope cantilever tip modulates the
      charge state of a QD in the Coulomb blockade regime. The charge dynamics of the
      dot, which is detected through its back-action on the capacitavely coupled
      cantilever, depends on the tunneling rate of the QD to a back-electrode. The
      density of states of the QD can therefore be measured through its effect on the
      energy dependence of tunneling rate. We present experimental data on individual 5
      nm colloidal gold nanoparticles that exhibit a near continuous density of state
      at 77 K. In contrast, our analysis of already published data on self-assembled
      InAs QDs at 4 K clearly reveals discrete degenerate energy levels. 

PMID- 25761143
TI  - Assessment of quality outcomes for robotic pancreaticoduodenectomy:
      identification of the learning curve.
AB  - IMPORTANCE: Quality assessment is an important instrument to ensure optimal
      surgical outcomes, particularly during the adoption of new surgical technology.
      The use of the robotic platform for complex pancreatic resections, such as the
      pancreaticoduodenectomy, requires close monitoring of outcomes during its
      implementation phase to ensure patient safety is maintained and the learning
      curve identified. OBJECTIVE: To report the results of a quality analysis and
      learning curve during the implementation of robotic pancreaticoduodenectomy
      (RPD). DESIGN, SETTING, AND PARTICIPANTS: A retrospective review of a
      prospectively maintained database of 200 consecutive patients who underwent RPD
      in a large academic center from October 3, 2008, through March 1, 2014, was
      evaluated for important metrics of quality. Patients were analyzed in groups of
      20 to minimize demographic differences and optimize the ability to detect
      statistically meaningful changes in performance. EXPOSURES: Robotic
      pancreaticoduodenectomy. MAIN OUTCOMES AND MEASURES: Optimization of
      perioperative outcome parameters. RESULTS: No statistical differences in
      mortality rates or major morbidity were noted during the study. Statistical
      improvements in estimated blood loss and conversions to open surgery occurred
      after 20 cases (600 mL vs 250 mL [P = .002] and 35.0% vs 3.3% [P < .001],
      respectively), incidence of pancreatic fistula after 40 cases (27.5% vs 14.4%; P
      = .04), and operative time after 80 cases (581 minutes vs 417 minutes [P <
      .001]). Complication rates, lengths of stay, and readmission rates showed
      continuous improvement that did not reach statistical significance. Outcomes for
      the last 120 cases (representing optimized metrics beyond the learning curve)
      included a mean operative time of 417 minutes, median estimated blood loss of 250
      mL, a conversion rate of 3.3%, 90-day mortality of 3.3%, a clinically significant
      (grade B/C) pancreatic fistula rate of 6.9%, and a median length of stay of 9
      days. CONCLUSIONS AND RELEVANCE: Continuous assessment of quality metrics allows
      for safe implementation of RPD. We identified several inflexion points
      corresponding to optimization of performance metrics for RPD that can be used as
      benchmarks for surgeons who are adopting this technology.

PMID- 25761144
TI  - An N-ethylated barbituric acid end-capped bithiophene as an electron-acceptor
      material in fullerene-free organic photovoltaics.
AB  - A new evaporable electron acceptor material for organic photovoltaics based on N
      ethyl barbituric acid bithiophene (EBB) has been demonstrated. Bilayer devices
      fabricated with this non-fullerene acceptor and boron subphthalocyanine chloride
      (SubPc) donor produce power conversion efficiencies as high as 2.6% with an
      extremely large open-circuit voltage approaching 1.4 V. 

PMID- 25761142
TI  - A glycine insertion in the estrogen-related receptor (ERR) is associated with
      enhanced expression of three cytochrome P450 genes in transgenic Drosophila
      melanogaster.
AB  - Insecticide-resistant Drosophila melanogaster strains represent a resource for
      the discovery of the underlying molecular mechanisms of cytochrome P450
      constitutive over-expression, even if some of these P450s are not directly
      involved in the resistance phenotype. For example, in select 4,4'
      dichlorodiphenyltrichloroethane (DDT) resistant strains the glucocorticoid
      receptor-like (GR-like) potential transcription factor binding motifs (TFBMs)
      have previously been shown to be associated with constitutively differentially
      expressed cytochrome P450s, Cyp12d1, Cyp6g2 and Cyp9c1. However, insects are not
      known to have glucocorticoids. The only ortholog to the mammalian glucocorticoid
      receptor (GR) in D. melanogaster is an estrogen-related receptor (ERR) gene,
      which has two predicted alternative splice isoforms (ERRa and ERRb). Sequencing
      of ERRa and ERRb in select DDT susceptible and resistant D. melanogaster strains
      has revealed a glycine (G) codon insertion which was only observed in the ligand
      binding domain of ERR from the resistant strains tested (ERR-G). Transgenic
      flies, expressing the ERRa-G allele, constitutively over-expressed Cyp12d1,
      Cyp6g2 and Cyp9c1. Only Cyp12d1 and Cyp6g2 were over-expressed in the ERRb-G
      transgenic flies. Phylogenetic studies show that the G-insertion appeared to be
      located in a less conserved domain in ERR and this insertion is found in multiple
      species across the Sophophora subgenera. 

PMID- 25761145
TI  - A functional Small Ubiquitin-like Modifier (SUMO) interacting motif (SIM) in the
      gibberellin hormone receptor GID1 is conserved in cereal crops and disrupting
      this motif does not abolish hormone dependency of the DELLA-GID1 interaction.
AB  - Plants survive adversity by modulating their growth in response to changing
      environmental signals. The phytohormone Gibberellic acid (GA) plays a central
      role in regulating these adaptive responses by stimulating the degradation of
      growth repressing DELLA proteins which accumulate during stress. The current
      model for GA signaling describes how this hormone binds to its receptor GID1 so
      promoting association of GID1 with DELLA, which then undergoes ubiquitin-mediated
      proteasomal degradation. Recent data revealed that conjugation of DELLAs to the
      Small Ubiquitin-like Modifier (SUMO) protein enables plants to modulate its
      abundance during environmental stress. This is achieved by SUMOylated DELLAs
      sequestering GID1 via its SUMO interacting motif (SIM) allowing non-SUMOylated
      DELLAs to accumulate leading to growth restraint under stress and potential yield
      loss. We demonstrate that GID1 proteins across the major cereal crops contain a
      functional SIM able to bind SUMO1. Site directed mutagenesis and yeast 2 hybrid
      experiments reveal that it is possible to disrupt the SIM-SUMO interaction motif
      without affecting the GA dependent DELLA-GID1 interaction and thereby uncoupling
      SUMO-mediated inhibition from DELLA degradation. Arabidopsis plants
      overexpressing a SIM mutant allele of GID1 perform better at relieving DELLA
      restraint than wild-type GID1. This evidence suggests that manipulating the SIM
      motif in the GA receptor may provide a possible route to developing stress
      tolerant crops plants. 

PMID- 25761146
TI  - Complex patients and interprofessional relationships: Perceptions of primary care
      nurse practitioners and primary care physicians.
AB  - PURPOSE: The literature describing primary care nurse practitioners (PCNPs) and
      primary care physicians (PCPs) suggests that PCNPs provide care to patients with
      less complicated diagnoses than their PCP colleagues. However, other literature
      suggests the contrary. Therefore, the purpose of this qualitative study was to
      understand how patients are assigned and cared for by primary care clinicians and
      how these clinicians relate to one another. Additionally we explore how PCNPs
      relate to physicians outside the practice. DATA SOURCES: Two nurse investigators
      conducted in-depth qualitative interviews with a nurse practitioner and a family
      medicine physician leader in each of 10 primary care practices. A content
      analysis was used to identify major themes. CONCLUSIONS: The participating PCNPs
      and PCPs have highly collaborative relationships. PCNPs often function
      independently, engage in reciprocal consultations with PCPs, and provide care to
      highly complex patients. In contrast to their relationships with practice
      colleagues, PCNP relationships with physicians outside the practice are
      disruptive. IMPLICATIONS FOR PRACTICE: These findings indicate that PCNPs are
      well positioned to assume responsibility for a diversity of primary care
      patients, including those with complex diagnoses. To promote the more effective
      integration of PCNPs, interprofessional barriers must be addressed by healthcare
      organizations and policy experts.

PMID- 25761147
TI  - Ibuprofen causes photocleavage through ROS generation and intercalates with DNA:
      a combined biophysical and molecular docking approach.
AB  - Ibuprofen is an important nonsteroidal anti-inflammatory drug endowed with
      various pharmacological and biological activities. In the present study, the
      photochemical properties of ibuprofen were evaluated by assaying the generation
      of various reactive oxygen species (ROS) such as superoxide, singlet oxygen and
      the hydroxyl radical. ROS generated by ibuprofen in the presence of white light
      causes DNA strand scission as observed by plasmid nicking assay. Ibuprofen
      induced ROS generation is also capable of causing DNA degradation in lymphocytes
      as observed by photocomet assay. ROS generation properties of ibuprofen were
      further strengthened by the formation of carbonyl groups in BSA and TBARS in
      linoleic acid as observed by carbonyl assay and lipid peroxidation assay
      respectively. We have also investigated the mode of interaction of ibuprofen with
      calf thymus DNA through a series of in vitro experiments. UV-visible spectroscopy
      established the formation of a complex between ibuprofen and Ct DNA. The steady
      state fluorescence experiments at different temperatures revealed a binding
      constant of ~10(4) L mol(-1), which is indicative of intercalative binding
      between ibuprofen and the DNA helix. Analysis of the various thermodynamic
      parameters DeltaG, DeltaH and DeltaS calculated at different temperatures
      indicated that the hydrogen bonds played a major role in the interaction. The
      intercalative binding mode is further confirmed by competitive displacement
      assays, urea denaturation, iodide quenching, viscosity measurements and CD
      analysis. In silico molecular docking revealed the binding of ibuprofen within
      the GC base pairs of DNA, confirming the intercalative binding mode. 

PMID- 25761148
TI  - Catalytic cyclization reactions of Huisgen zwitterion with alpha-ketoesters by in
      situ chemoselective phosphine oxide reduction.
AB  - The first examples of catalytic cyclization reactions between the Huisgen
      zwitterion and alpha-ketoester derivatives are reported. The use of phenylsilane
      with a substoichiometric amount of bis(p
      nitrophenyl)phosphate/diisopropylethylamine proved to be crucial for the in situ
      reduction of the phosphine oxide formed during the reaction. The optimized
      protocol is applied to alkyl or aryl ketoesters, furnishing either the
      corresponding cycloadducts or the hydrazone derivatives, depending on the
      substitution patterns of the substrates, in moderate to good yields (up to 80%
      yield, 18 examples). 

PMID- 25761149
TI  - Use of an employment advisory service by cancer survivors.
AB  - Employment issues for cancer survivors (CS) were investigated from the
      perspective of Northern Ireland government general employment advisors. An e
      survey was designed and developed based on the results of a scoping search of
      journal articles, previously validated questionnaires and relevant related
      surveys; discussions of draft versions of the e-survey and method with lead
      representatives of stakeholder organizations; and a pilot study with seven
      prospective respondents. The e-survey and subsequent reminder to employment
      advisors were distributed internally by the government employment advisory
      agency. The e-survey was completed by 78/156 (50%) advisors, the majority of whom
      (74%) received a request for advice in the last year from at least one CS. Most
      CS used the employment service less than 1 year (52%) or 1 year or more after
      treatment (32%). Fatigue was the most commonly reported barrier to returning to
      work (10%) and staying in work (14%), and a supportive employer was the top
      facilitating factor in returning to (21%) and continuing in (27%), employment.
      Although most advisors had a positive attitude about a CS's capacity to return to
      work, half were uncertain about how best to advise cancer survivors. 

PMID- 25761151
TI  - Unknown primary: diagnostic issues in the biological endoscopy and positron
      emission tomography scan era.
AB  - PURPOSE OF REVIEW: There is no general agreement on which diagnostic procedures
      are required and optimal in searching for primary tumors among patients with
      cervical metastasis of unknown primary (CUP). Because of the rising incidence of
      human papillomavirus (HPV)-associated oropharyngeal carcinoma, it is reasonable
      to assume that the number of small oropharyngeal tumors with neck metastasis will
      increase. The purpose of this review is to highlight the diagnostic approaches
      more useful in detecting such lesions. RECENT FINDINGS: After the introduction of
      the narrow band imaging technique, positron emission tomography-computed
      tomography, and transoral diagnostic procedures, the accuracy in discovering the
      primary lesion is up to 80-90%. By far, most primaries arise in the oropharynx,
      especially among patients with p16/HPV-positive CUP. SUMMARY: The oropharynx is
      the most likely primary site in patients with CUP, especially in p16/HPV-positive
      cases. By utilizing recent techniques, a high diagnostic accuracy in detecting
      the primary tumor is achievable; this may offer better survival rates with cost
      effective efforts. We recommend some approaches for the diagnostic protocol used
      in searching for primary tumors in patients with CUP.

PMID- 25761152
TI  - Oropharyngeal cancer treatment: the role of transoral surgery.
AB  - PURPOSE OF REVIEW: This article reviews literature pertaining to squamous cell
      carcinoma (SCC) of the oropharynx and the evolution of transoral surgical (TOS)
      techniques for its management. Oncologists are recognizing a changing pattern in
      the cause of oropharyngeal cancer, namely the increasing incidence of HPV
      associated tumors. An effort is underway to reduce the morbidity of treatment
      without jeopardizing survival. This is a timely discussion for reassessment of
      current standards of care and opening dialogue on treatment de-escalation.
      Transoral approaches including transoral laser microsurgery (TLM) and transoral
      robotic surgery (TORS) have revolutionized the surgical approach to SCC. RECENT
      FINDINGS: The incidence of HPV-related oropharyngeal SCC is increasing at
      epidemic rates. Although there are no studies comparing nonsurgical treatment to
      TOS in a randomized controlled fashion, there is an abundance of retrospective
      and prospective reports of TORS and TLM. Both early and advanced-stage
      oropharyngeal tumors can be managed successfully with surgery, with or without
      adjuvant therapy. SUMMARY: Although there are no hard scientific differences in
      oncologic outcomes between primary chemoradiation protocols and primary TOS-based
      approaches, retrospective comparisons support an advantage of primary surgery. In
      addition, functional outcomes may be superior following TOS treatment. Management
      of oropharyngeal SCC will most likely continue to be multidisciplinary with an
      ongoing effort to de-escalate treatment to reduce morbidity.

PMID- 25761150
TI  - Synthesis of 3,8-dichloro-6-ethyl-1,2,5,7-tetramethyl-BODIPY from an asymmetric
      dipyrroketone and reactivity studies at the 3,5,8-positions.
AB  - The asymmetric BODIPY 1 a (BODIPY=4,4-difluoro-4-bora-3a,4a-diaza-s-indacene),
      containing two chloro substituents at the 3,8-positions and a reactive 5-methyl
      group, was synthesized from the asymmetric dipyrroketone 3, which was readily
      obtained from available pyrrole 2 a. The reactivity of 3,8-dichloro-6-ethyl
      1,2,5,7-tetramethyl-BODIPY 1 a was investigated by using four types of reactions.
      This versatile BODIPY undergoes regioselective Pd(0) -catalyzed Stille coupling
      reactions and/or regioselective nucleophilic addition/elimination reactions,
      first at the 8-chloro and then at the 3-chloro group, using a variety of
      organostannanes and N-, O-, and S-centered nucleophiles. On the other hand, the
      more reactive 5-methyl group undergoes regioselective Knoevenagel condensation
      with an aryl aldehyde to produce a monostyryl-BODIPY, and oxidation with 2,3
      dichloro-5,6-dicyano-1,4-benzoquinone (DDQ) gives the corresponding 5-formyl
      BODIPY. Investigation of the reactivity of asymmetric BODIPY 1 a led to the
      preparation of a variety of functionalized BODIPYs with lambdamax of absorption
      and emission in the ranges 487-587 and 521-617 nm, respectively. The longest
      absorbing/emitting compound was the monostyryl-BODIPY 16, and the largest Stokes
      shift (49 nm) and fluorescence quantum yield (0.94) were measured for 5-thienyl-8
      phenoxy-BODIPY 15. The structural properties (including 16 X-ray structures) of
      the new series of BODIPYs were investigated. 

PMID- 25761153
TI  - Pathological changes of the inner ear cochlea in different time windows of murine
      cytomegalovirus-induced hearing loss in a mouse model.
AB  - CONCLUSIONS: Murine congenital cytomegalovirus (CMV) (MCMV) infection of the
      inner ear cochlea, which caused continuous pathological change, occurred on the
      third day after intracerebral injection and persisted for a very long time.
      OBJECTIVE: Our study used the MCMV-induced hearing loss neonatal mouse model to
      investigate the pathological changes of the cochlea in different time windows.
      METHODS: Sixty newborn BALB/c mice were randomly and equally divided into the
      experimental group (MCMV intracerebral injection) and control group (normal
      saline intracerebral injection). At 1, 3, 5, 7, and 21 days after intracerebral
      injection, cochleas were extracted and evaluated by MCMV-DNA PCR analysis and
      histopathological examination. RESULTS: Two mice died before the end of the
      experiment in the experimental group, while there were no deaths in the control
      group. In the experimental group, the MCMV-DNA PCR samples did not show positive
      results in the gel electrophoresis until the 3-21 days after intracerebral
      injection, while no positive result was found in the control group. Pathological
      changes including hemorrhage and inflammatory cell infiltration of the scala
      vestibule and scala tympani began on the third day, spiral ganglion cell gap
      widening and cell thinning began on the seventh day, and scala tympani fibrosis
      began on the 14th day.

PMID- 25761154
TI  - Mechanical responses of cancer cells on nanoscaffolds for adhesion size control.
AB  - A mechano-reciprocal interaction plays a critical role for cancer cells searching
      for favorable metastasis sites. For this study, we utilized nanoscaffolds that
      can control the maturation of focal adhesions in order to investigate how cancer
      cells mechanically respond to their nanoenvironments. We found that prostate
      cancer cells showed linearly decreasing proliferation rate and mechanical
      stiffness as the size of nanoislands on nanoscaffolds where the cells were grown
      decreases. This mechanical signature was exacerbated for less metastatic prostate
      cancer cells. However, there was no dependence of mechanical responses on the
      geometric properties of nanoscaffolds for breast cancer cells, despite the acute
      inhibition of adhesion and the abrupt mechanical changes. We believe that our
      holistic approach that utilizes atomic force microscopy (AFM) and nanoscaffolds
      can reveal which mechano-reciprocal interactions are crucial for metastasis and,
      thus, provide useful information for anti-cancer drug development targeting
      integrin-associated signaling. 

PMID- 25761155
TI  - Striving for safety: communicating and deciding in sociotechnical systems.
AB  - How do communications and decisions impact the safety of sociotechnical systems?
      This paper frames this question in the context of a dynamic system of nested sub
      systems. Communications are related to the construct of observability (i.e. how
      components integrate information to assess the state with respect to local and
      global constraints). Decisions are related to the construct of controllability
      (i.e. how component sub-systems act to meet local and global safety goals). The
      safety dynamics of sociotechnical systems are evaluated as a function of the
      coupling between observability and controllability across multiple closed-loop
      components. Two very different domains (nuclear power and the limited service
      food industry) provide examples to illustrate how this framework might be
      applied. While the dynamical systems framework does not offer simple
      prescriptions for achieving safety, it does provide guides for exploring specific
      systems to consider the potential fit between organisational structures and work
      demands, and for generalising across different systems regarding how safety can
      be managed. PRACTITIONER SUMMARY: While offering no simple prescriptions about
      how to achieve safety in sociotechnical systems, this paper develops a
      theoretical framework based on dynamical systems theory as a practical guide for
      generalising from basic research to work domains and for generalising across
      alternative work domains to better understand how patterns of communication and
      decision-making impact system safety.

PMID- 25761156
TI  - Two steps forward...

PMID- 25761157
TI  - Parental contributions and separation anxiety on adolescents' cannabis use: a
      preliminary study based on French high school students.
AB  - BACKGROUND: Separation anxiety (SA) among adolescents remains a very rare
      diagnosis. According to some authors, behavioral disorders may arise from SA
      disorders. This study evaluated the relationship between cannabis use and family
      functioning among adolescent cannabis users. METHOD: Adolescents (n = 336)
      completed questionnaires about the frequency of their cannabis use, SA symptoms
      in adult populations, dysfunctional separation-individuation processes in early
      adolescence, parental types as perceived by the children, and depression
      symptoms. RESULTS: Adolescent users of cannabis obtained significantly higher
      scores than adolescent nonusers of cannabis on the Anxiety Separation Adulthood
      scale (p < .005) and lower scores on the "care" subscale about parents'
      representations ("mother," p < .01; "father," p < .001). The logistic regression
      analysis indicated that SA disorders and care significantly encouraged cannabis
      use. DISCUSSION: Among adolescents, cannabis use is perceived as a solution that
      reduces the intolerable feelings of SA disorder. If successful separation
      individuation allows autonomy, the results indicate that cannabis use hides
      individuation problems. The use of this substance allows adolescents to express
      their personality and differentiate themselves from others through marginal
      behavior.

PMID- 25761158
TI  - Ketamine users have high rates of psychosis and/or depression.
AB  - Ketamine has been linked to psychosis and used in the treatment of depression.
      However, no study has examined the prevalence of psychotic and depressive
      disorders in dependent ketamine users. This study aimed to examine the frequency
      of various psychopathologies among a series of patients seeking treatment for
      ketamine use in Hong Kong, China. The case records of 129 patients with a history
      of ketamine use receiving treatment at three substance use clinics between
      January 2008 and August 2012 were retrieved for data collection. Patients'
      demographic data, patterns of substance misuse, and comorbid psychiatric
      diagnoses were recorded and entered into analyses. The mean age of onset and
      length of ketamine use were 17.7 +/- 4.4 and 8.7 +/- 5.7 years, respectively. All
      patients were dependent on ketamine at the time of data collection. Multiple
      substance misuse was common. Eighty-four of the 129 (65.1%) patients were found
      to have comorbid psychiatric disorders, most commonly substance-induced psychotic
      disorder (31.8%) followed by depressive disorder (27.9%). Psychosis and/or
      depression were common in ketamine-dependent patients referred to a psychiatric
      substance use clinic. The findings provide evidence of an association between
      chronic ketamine use and the presence of psychosis and/or depression. The results
      raise the issue of safety when using ketamine in the long-term treatment of
      depression. 

PMID- 25761160
TI  - Energy drink consumption patterns and associated factors among nursing students:
      a descriptive survey study.
AB  - BACKGROUND: This study was conducted to examine energy drink consumption patterns
      among nursing students and to identify related factors that may influence those
      students' intake levels. METHODS: The subjects were nursing students from seven
      universities located in the Chungcheong Province of Korea. A total of 1,620
      questionnaires were used for analysis. RESULTS: Of the 1,620 nursing students,
      1,265 students (78.1%) reported having consumed energy drinks. The average amount
      of energy drink consumption among the nursing students when studying for their
      most recent midterm examination was 1.63 +/- 2.64 cans per week, and the number
      of energy drink cans drunk during that time spanned 1-30 per week. The major
      reason given for energy drink intake was combating fatigue. Eleven percent of the
      participants always checked ingredient levels. Mixing energy drinks with alcohol
      was not a popular choice. The side effect most reported by nursing students was
      that of palpitations (27.8%). Factors affecting energy drink intake included
      gender and monthly allowance amounts. CONCLUSIONS: Many nursing students in this
      study had tried energy drinks, with some of them reporting the use of excessive
      amounts. Gender and monthly allowance amounts were affecting factors of energy
      drink intake. Precise labeling that includes all ingredients and their amounts is
      necessary to prevent future health problems. Nursing students' education should
      include an overview of energy drinks and their drawbacks as part of their
      nutrition or health education coursework.

PMID- 25761159
TI  - A review of treatment options for co-occurring methamphetamine use disorders and
      depression.
AB  - Co-occurring methamphetamine use and depression interferes with treatment
      outcomes. Female methamphetamine users are known to have higher rates of
      depression than male methamphetamine users, although this is also true for the
      general population. There are limited treatment options for the management of
      depression among methamphetamine users. In this integrative review, we summarize
      data on treatment strategies for co-occurring depression and methamphetamine use
      disorders. English-language articles were identified from PsychINFO, CINAHL,
      PubMed, and Medline as well as from reference lists of key articles. Search terms
      included "methamphetamine," "depression," and "treatment." Research articles
      describing psychological (n = 3), pharmacological (n = 6), nutritional supplement
      (n = 1), and psychological combined with pharmacological (n = 3) approaches for
      the treatment of methamphetamine use or withdrawal and/or depression are included
      in this review. Psychological and combination of psychological with
      pharmacological approaches have not been shown to be effective in treating these
      co-occurring conditions. Antidepressants have been determined to be ineffective
      and/or to introduce side effects. Gender differences with response to treatment
      were examined in only one of the published studies. There is a large gap in
      knowledge regarding treatment of co-occurring methamphetamine use disorders and
      depression. Considering that female methamphetamine users experience higher rates
      of depression than men, a focus on gender-specific treatment approaches is
      warranted. 

PMID- 25761161
TI  - The youth alternative solutions program: evaluating a hospital-based intervention
      for adolescent substance use.
AB  - Issues of alcohol and drug use are more pronounced during adolescence than at any
      other period of the lifespan and represent a significant public health concern in
      the United States. As a result, there is currently a need for research on
      developmentally appropriate interventions for adolescent substance use (SU).
      Nurses and other mental health professionals working with adolescents need
      effective evidenced-based programs to refer clients having issues with SU. The
      current pilot study evaluated the effectiveness of the Youth Alternative
      Solutions Program, a hospital-based intervention program at a Level I trauma
      center in Southern California that partners with community stakeholders to
      accomplish its goals. A sample of 27 adolescents was recruited from August 2010
      until October 2011. Twenty-seven total participants completed both pretest and
      posttest questionnaires; 14 of these participants also completed follow-up data
      collection. Results indicated a significant increase in negative alcohol outcome
      expectancies between the three study time points. More comprehensive studies of
      the Youth Alternative Solutions Program should be conducted in the future to
      determine the utility of hospital-based SU interventions and to provide evidence
      of the program's long-term effects. 

PMID- 25761162
TI  - Smoking and desire to quit smoking behavior in a sample of Turkish adolescents.
AB  - INTRODUCTION: The age of starting the habit of smoking, one of the top causes of
      many illnesses, is usually in the period of adolescence. This study was conducted
      to determine students' smoking status and to explore their desire to quit and
      their experiences during the cessation process. METHODS: This descriptive study
      was performed with 934 adolescents between the ages of 14 and 20 years at a
      vocational high school located in Istanbul, Turkey. The data were collected by
      using a survey form. RESULTS: The mean age of the adolescents was 16.38 +/- 1.12
      years. Among the adolescents, 90.3% were male. Of the group, 29.9% reported that
      they had smoked at least once, and 12.1% of the participants smoked regularly.
      Among the students who smoked, 80% reported that they wanted to quit smoking.
      Among the smokers, 55.2% reported that they tried to quit smoking but could only
      stop smoking for a period of between 1 day and 1 month at maximum (71.4%). A
      group of 68.9% reported that they wanted to quit because they were afraid of
      getting sick in the future, 28.8% indicated economic reasons to quit smoking, and
      24.2% reported that they wanted to stop smoking because they did not want to
      damage the environment. CONCLUSION: More than half of the smokers among the
      students had tried to stop smoking, but most of them had failed to quit. These
      results indicate that schools need programs for the cessation and the prevention
      of smoking.

PMID- 25761163
TI  - A comparative review of guides for implementing alcohol screening and brief
      interventions into trauma and primary care settings.
AB  - The likelihood that a patient is currently using alcohol is high across all
      health care settings with almost one in four persons in the United States aged 12
      years or over reporting excessive drinking on at least one occasion in the past
      30 days. Screening and brief intervention (SBI) is an evidence-based approach to
      help decrease alcohol-related harm among persons seeking health care. The Centers
      for Disease Control and Prevention and the Committee on Trauma, American College
      of Surgeons, have provided guidelines for implementation of an SBI program within
      a health care organization. This column provides a comparative overview of three
      of these guides. These guides provide practical information to help nurses and
      other health care providers with the planning and implementation of alcohol SBI
      into routine practice. 

PMID- 25761164
TI  - The Comprehensive Addiction and Recovery Act of 2014.

PMID- 25761165
TI  - Over 30 years of support to nurses with impaired practice: the Massachusetts
      Nurses Association Peer Assistance Program.

PMID- 25761168
TI  - The Effects of Portulaca oleracea on Hypoxia-Induced Pulmonary Edema in Mice.
AB  - Portulaca oleracea L. (PO) is known as "a vegetable for long life" due to its
      antioxidant, anti-inflammatory, and other pharmacological activities. However,
      the protective activity of the ethanol extract of PO (EEPO) against hypoxia
      induced pulmonary edema has not been fully investigated. In this study, we
      exposed mice to a simulated altitude of 7000 meters for 0, 3, 6, 9, and 12 h to
      observe changes in the water content and transvascular leakage of the mouse lung.
      It was found that transvascular leakage increased to the maximum in the mouse
      lung after 6 h exposure to hypobaric hypoxia. Prophylactic administration of EEPO
      before hypoxic exposure markedly reduced the transvascular leakage and oxidative
      stress, and inhibited the upregulation of NF-kB in the mouse lung, as compared
      with the control group. In addition, EEPO significantly reduced the levels of
      proinflammatory cytokines and cell adhesion molecules in the lungs of mice, as
      compared with the hypoxia group. Our results show that EEPO can reduce initial
      transvascular leakage and pulmonary edema under hypobaric hypoxia conditions.

PMID- 25761169
TI  - Centile curves and reference values for height, body mass, body mass index and
      waist circumference of Peruvian children and adolescents.
AB  - This study aimed to provide height, body mass, BMI and waist circumference (WC)
      growth centile charts for school-children, aged 4-17 years, from central Peru,
      and to compare Peruvian data with North-American and Argentinean references. The
      sample consisted of 8753 children and adolescents (4130 boys and 4623 girls) aged
      4 to 17 years, from four Peruvian cities: Barranco, La Merced, San Ramon and
      Junin. Height, body mass and WC were measured according to standardized
      techniques. Centile curves for height, body mass, BMI and WC were obtained
      separately for boys and girls using the LMS method. Student t-tests were used to
      compare mean values. Overall boys have higher median heights than girls, and the
      50th percentile for body mass increases curvilinearly from 4 years of age
      onwards. In boys, the BMI and WC 50th percentiles increase linearly and in girls,
      the increase presents a curvilinear pattern. Peruvian children are shorter,
      lighter and have higher BMI than their counterparts in the U.S. and Argentina; in
      contrast, age and sex-specific WC values are lower. Height, body mass and WC of
      Peruvian children increased with age and variability was higher at older ages.
      The growth patterns for height, body mass, BMI and WC among Peruvian children
      were similar to those observed in North-American and Argentinean peers. 

PMID- 25761170
TI  - School bonds and the onset of substance use among Korean youth: an examination of
      social control theory.
AB  - This study examined the association between school bonds and the onset of
      substance use among adolescents in South Korea. Based on Hirschi's social control
      theory, this study tested the roles of teacher attachment, educational
      aspiration, extracurricular activities, and rule internalization--four elements
      of social bonds within the school setting--in delayed initiation of alcohol
      drinking and cigarette smoking. Discrete-time logistic regression was used to
      analyze five waves of the Korea Youth Panel Survey (N=3449 at baseline), a
      nationally representative sample of Korean youth. Stronger teacher attachment,
      higher educational aspiration, and higher rule internalization were correlated
      with delayed onset of alcohol drinking and cigarette smoking. On the other hand,
      participation in school extracurricular activities was positively associated with
      the onset of alcohol drinking, but not statistically significantly linked with
      the onset of cigarette smoking. These findings suggest that early prevention
      strategies for youth substance use should specifically target school-related
      factors that represent social bonds developed among youth.

PMID- 25761171
TI  - Decoding the jargon of bottom-up metabolic systems biology.

PMID- 25761172
TI  - Theoretical insight into the mechanism of gold(I)-catalyzed rearrangement of 2
      propargyl 2H-azirines to pyridines.
AB  - The title reaction is investigated in detail theoretically using density
      functional theory. After 5-endo-dig cyclization by nucleophilic attack, five
      possible pathways are taken into account in this work: direct ring expansion
      followed or accompanied by proton-transfer (paths A and B, respectively), 1,3
      cationic migration (path C), proton-transfer before ring expansion (path D), and
      processing via a gold-nitrene (path E). Results indicate that the reaction would
      undergo the favored sequential pathway (path A) rather than other pathways.
      Moreover, the concerted mechanism (path B), which is designed to account for the
      selectivity of product in the experiment, would be unlikely in the reaction. The
      selectivity of product could be explained by the hindrance of ligand (t-BuXPhos)
      and the stability of the carbocation. Moreover, the binding energy of product
      complexes could account for the observed reaction rate. 

PMID- 25761173
TI  - Treatments for shoulder impingement syndrome: a PRISMA systematic review and
      network meta-analysis.
AB  - Many treatments for shoulder impingement syndrome (SIS) are available in clinical
      practice; some of which have already been compared with other treatments by
      various investigators. However, a comprehensive treatment comparison is lacking.
      Several widely used electronic databases were searched for eligible studies. The
      outcome measurements were the pain score and the Constant-Murley score (CMS).
      Direct comparisons were performed using the conventional pair-wise meta-analysis
      method, while a network meta-analysis based on the Bayesian model was used to
      calculate the results of all potentially possible comparisons and rank
      probabilities. Included in the meta-analysis procedure were 33 randomized
      controlled trials involving 2300 patients. Good agreement was demonstrated
      between the results of the pair-wise meta-analyses and the network meta-analyses.
      Regarding nonoperative treatments, with respect to the pain score, combined
      treatments composed of exercise and other therapies tended to yield better
      effects than single-intervention therapies. Localized drug injections that were
      combined with exercise showed better treatment effects than any other treatments,
      whereas worse effects were observed when such injections were used alone.
      Regarding the CMS, most combined treatments based on exercise also demonstrated
      better effects than exercise alone. Regarding surgical treatments, according to
      the pain score and the CMS, arthroscopic subacromial decompression (ASD) together
      with treatments derived from it, such as ASD combined with radiofrequency and
      arthroscopic bursectomy, showed better effects than open subacromial
      decompression (OSD) and OSD combined with the injection of platelet-leukocyte
      gel. Exercise therapy also demonstrated good performance. Results for
      inconsistency, sensitivity analysis, and meta-regression all supported the
      robustness and reliability of these network meta-analyses. Exercise and other
      exercise-based therapies, such as kinesio taping, specific exercises, and
      acupuncture, are ideal treatments for patients at an early stage of SIS. However,
      low-level laser therapy and the localized injection of nonsteroidal anti
      inflammatory drugs are not recommended. For patients who have a long-term disease
      course, operative treatments may be considered, with standard ASD surgery
      preferred over arthroscopic bursectomy and the open surgical technique for
      subacromial decompression. Notwithstanding, the choice of surgery should be made
      cautiously because similar outcomes may also be achieved by the implementation of
      exercise therapy.

PMID- 25761174
TI  - Efficacy and safety of antiintegrin antibody for inflammatory bowel disease: a
      systematic review and meta-analysis.
AB  - We sought to evaluate the safety and efficacy of available biologics that inhibit
      T-cell migration by blocking alpha4beta7 integrins in inflammatory bowel
      diseases. The aim of this study is to evaluate whether Crohn disease (CD)
      patients receiving either vedolizumab or natalizumab have any different effect in
      CD Activity Index (CDAI). Using Medline, Excerpta Medica dataBASE, Cochrane
      Central Register of Controlled Trials (CENTRAL), and Google Scholar until October
      31, 2013, we identified 10 studies examining the safety and efficacy of specific
      integrin inhibitors-vedolizumab, which targets an epitope comprising the
      alpha4beta7 heterodimer; natalizumab, which recognizes the alpha4 integrin
      subunit; etrolizumab, which is specific for the beta7 subunit-in the treatment of
      CD and ulcerative colitis (UC). CD patients receiving either vedolizumab or
      natalizumab demonstrated a modest increase in remission rate, when compared with
      that of the placebo group. Further, although both treatments reduced the CDAI
      slightly, the observed clinical response was less robust than that of the
      remission rate. UC patients treated with vedolizumab and natalizumab were found
      to show more prominent increases in both remission and clinical response,
      compared with placebo, than patients with CD. Etrolizumab, however, was not found
      to significantly affect either response or remission rates in UC patients.
      Biologics targeting integrins show promise as therapeutics in the treatment of
      inflammatory bowel disease in patients who are either nonresponsive or intolerant
      to traditional approaches, though further research is necessary to optimize
      treatment efficacies.

PMID- 25761175
TI  - A case report on the diagnosis of a rare pleural tumor with endobronchial
      ultrasound: breaking new boundaries.
AB  - Convex endobronchial ultrasound (C-EBUS)-guided transbronchial needle aspiration
      (TBNA) is an effective tool for the diagnosis of hilar, mediastinal, and central
      parenchymal lung lesions. However, it has a limited utility for pleural-based
      masses. We report a unique case of a pleural synovial sarcoma recurrence that was
      diagnosed by C-EBUS. The patient had a history of inguinal synovial sarcoma. He
      presented with cough and chest pain. Imaging of chest revealed large right
      pleural mass. Bronchoscopy with EBUS-TBNA diagnosed pleural recurrence of
      synovial sarcoma. He underwent radical resection and pathological examination
      confirmed the diagnosis of pleural synovial sarcoma. He experienced complete
      recovery and resolution of symptoms. Synovial sarcoma should be included in the
      differential diagnosis of pleural masses. Convex EBUS-guided biopsies can provide
      adequate diagnosis of large pleural tumors adjacent to the central airways
      without need for more invasive diagnostic procedures.

PMID- 25761176
TI  - Demographics and characterization of 10,282 Randall plaque-related kidney stones:
      a new epidemic?
AB  - Renal stone incidence has progressively increased in industrialized countries,
      but the implication of Randall plaque in this epidemic remains unknown. Our
      objectives were to determine whether the prevalence of Randall plaque-related
      stones increased during the past decades after having analyzed 30,149 intact
      stones containing mainly calcium oxalate since 1989 (cross-sectional study), and
      to identify determinants associated with Randall plaque-related stones in
      patients (case-control study). The proportion of Randall plaque-related stones
      was assessed over 3 time periods: 1989-1991, 1999-2001, and 2009-2011. Moreover,
      we analyzed clinical and biochemical parameters of 105 patients affected by
      calcium oxalate stones, with or without plaque. Of 30,149 calcium oxalate stones,
      10,282 harbored Randall plaque residues (34.1%). The prevalence of Randall plaque
      related stones increased dramatically during the past years. In young women, 17%
      of calcium oxalate stones were associated with Randall plaque during the 1989
      1991 period, but the proportion rose to 59% 20 years later (P < 0.001). Patients
      with plaques experienced their first stone-related event earlier in life as
      compared with those without plaque (median age 26 vs 34 years, P = 0.02), had
      increased ionized serum calcium levels (P = 0.04), and increased serum
      osteocalcin (P = 0.001) but similar 25-hydroxyvitamin D levels. The logistic
      regression analysis showed that age (odds ratio [OR] 0.96, confidence interval
      [CI] 0.926-0.994, P = 0.02), weight (OR 0.97, CI 0.934-0.997, P = 0.03), and
      osteocalcin serum levels (OR 1.12, CI 1.020-1.234, P = 0.02) were independently
      associated with Randall plaque. The prevalence of the FokI f vitamin D receptor
      polymorphism was higher in patients with plaque (P = 0.047). In conclusion, these
      findings point to an epidemic of Randall plaque-associated renal stones in young
      patients, and suggest a possible implication of altered vitamin D response.

PMID- 25761177
TI  - Coping strategies for health and daily-life stressors in patients with rheumatoid
      arthritis, ankylosing spondylitis, and gout: STROBE-compliant article.
AB  - This article aims to identify the strategies for coping with health and daily
      life stressors of Mexican patients with chronic rheumatic disease. We analyzed
      the baseline data of a cohort of patients with rheumatoid arthritis (RA),
      ankylosing spondylitis (AS), and gout. Their strategies for coping were
      identified with a validated questionnaire. Comparisons between health and daily
      life stressors and between the 3 clinical conditions were made. With regression
      analyses, we determined the contribution of individual, socioeconomic,
      educational, and health-related quality-of-life variables to health status and
      coping strategy. We identified several predominant coping strategies in response
      to daily-life and health stressors in 261 patients with RA, 226 with AS, and 206
      with gout. Evasive and reappraisal strategies were predominant when patients cope
      with health stressors; emotional/negative and evasive strategies predominated
      when coping with daily-life stressors. There was a significant association
      between the evasive pattern and the low short-form health survey (SF-36) scores
      and health stressors across the 3 diseases. Besides some differences between
      diagnoses, the most important finding was the predominance of the evasive
      strategy and its association with low SF-36 score and high level of pain in
      patients with gout. Patients with rheumatic diseases cope in different ways when
      confronted with health and daily-life stressors. The strategy of coping differs
      across diagnoses; emotional/negative and evasive strategies are associated with
      poor health-related quality of life. The identification of the coping strategies
      could result in the design of psychosocial interventions to improve self
      management.

PMID- 25761178
TI  - Circadian rhythm disruption was observed in hand, foot, and mouth disease
      patients.
AB  - Hand, foot, and mouth disease (HFMD) with central nerve system complications may
      rapidly progress to fulminated cardiorespiratory failure, with higher mortality
      and worse prognosis. It has been reported that circadian rhythms of heart rate
      (HR) and respiratory rate are useful in predicting prognosis of severe
      cardiovascular and neurological diseases. The present study aims to investigate
      the characteristics of the circadian rhythms of HR, respiratory rate, and
      temperature in HFMD patients with neurological complications. Hospitalized HFMD
      patients including 33 common cases (common group), 61 severe cases (severe
      group), and 9 critical cases (critical group) were contrasted retrospectively.
      Their HR, respiratory rate, and temperatures were measured every 4 hours during
      the first 48-hour in the hospital. Data were analyzed with the least-squares fit
      of a 24-hour cosine function by the single cosinor and population-mean cosinor
      method. Results of population-mean cosinor analysis demonstrated that the
      circadian rhythm of HR, respiratory rate, and temperature was present in the
      common and severe group, but absent in the critical group. The midline-estimating
      statistic of rhythm (MESOR) (P = 0.016) and acrophase (P < 0.01) of temperature
      and respiratory rate were significantly different among 3 groups. But no
      statistical difference of amplitude in temperature and respiratory rate was
      observed among the 3 groups (P = 0.14). MESOR value of HR (P < 0.001) was
      significantly different in 3 groups. However, amplitude and acrophase revealed no
      statistical difference in circadian characteristics of HR among 3 groups.
      Compared with the common group, the MESOR of temperature and respiratory rate was
      significantly higher, and acrophase of temperature and respiratory rate was 2
      hours ahead in the severe group, critical HFMD patients lost their population
      circadian rhythm of temperature, HR, and respiratory rate. The high values of
      temperature and respiratory rate for the common group were concentrated between 3
      and 9 PM, whereas those for the severe group were more dispersive. And the high
      values for the critical group were equally distributed in 24 hours of the day.
      Circadian rhythm of patients' temperature in the common group was the same as the
      normal rhythm of human body temperature. Circadian rhythm of patients'
      temperature, HR and respiratory rate in 3 groups were significantly different.

PMID- 25761179
TI  - Circulating microRNAs as biomarkers in hepatocellular carcinoma screening: a
      validation set from China.
AB  - Hepatocellular carcinoma (HCC) is a global public health concern. Current
      diagnostic methods show poor performance in early-stage HCC detection.
      Accumulating evidences revealed the great potential of microRNAs (miRNAs) as
      noninvasive biomarkers in HCC detection. In this study, we examined the
      diagnostic performance of serum miR-10b, miR-106b, and miR-181a for HCC screening
      in China. Furthermore, a systematic review of previous related studies was
      conducted to confirm our results. One hundred eight participants including 27 HCC
      patients, 31 chronic liver disease (CLD) patients, and 50 healthy people were
      recruited in this study. Blood specimen was drawn from each participant to
      extract serum miRNAs. Statistical analyses were performed to assess the 3 miRNAs
      levels in HCC, CLD patients, and normal controls. A meta-analysis was conducted
      to further assess the diagnostic value of miRNAs in HCC detection based on
      previous studies. All these miRNAs (miR-10b, miR-181a, miR-106b) could well
      discriminate HCC patients from normal controls, with area under the receiver
      operating characteristic curve (AUC) values of 0.85 (95% confidence interval
      [CI]: 0.76-0.94), 0.82 (95% CI: 0.72-0.91), and 0.89 (95% CI: 0.81-0.97),
      respectively. In addition, these miRNAs could distinguish HCC cases from CLD
      controls with a medium accuracy. However, the ability of these miRNAs in
      differentiating CLD patients from normal controls was not satisfactory. Panel of
      these miRNAs displayed a better performance compared with single miRNA assay,
      with AUC values of 0.94 (95% CI: 0.89-0.99) in discriminating HCC patients from
      normal controls and 0.91 (95% CI: 0.80-0.97) in discriminating HCC patients from
      CLD controls. Results of meta-analysis of previous studies combined with the
      current study suggested that circulating miRNAs could well differentiate HCC from
      normal controls, with AUC values of 0.86 (95% CI: 0.82-0.89) for single miRNA
      assay and 0.94 (95% CI: 0.91-0.96) for miRNA panel assay. Serum miR-10b, miR
      106b, and miR-181a have great potential to serve as accurate and noninvasive
      biomarkers for HCC preliminary screening. Meta-analysis of previous studies
      combined with current study further confirmed that circulating miRNAs could play
      an important role in HCC detection. Further large-scale studies are needed to
      confirm the clinical significance of circulating miRNAs in HCC screening.

PMID- 25761180
TI  - Blood pressure reverse-dipping is associated with early formation of carotid
      plaque in senior hypertensive patients.
AB  - Nocturnal variations in blood pressure (BP) were associated with carotid intima
      media thickness. However, the precise relationship between circadian variations
      of BP and carotid plaques remains unknown. Therefore, the prognostic value of
      reverse-dipper pattern of BP for carotid plaque was investigated. In this cross
      sectional study, a total of 524 hypertensive patients were recruited and
      evaluated with ambulatory BP monitoring between April 2012 and June 2013. Carotid
      plaque was classified into Grade 0 (normal or no observable plaque), Grade 1
      (mild stenosis, 1%-24% narrowing), and Grade 2 (moderate stenosis, >=25%
      narrowing). Multinomial logistic regression was applied to analyze the
      relationship between different degrees of carotid plaque and ambulatory BP
      monitoring results. Reverse-dipper pattern of BP was more common in older
      patients, smokers, and those with elevated fasting glucose. The incidences of
      coronary artery disease, lacunar infarction, and diabetes were also higher among
      hypertensive with reverse-dipper pattern. Multinomial logistic regression
      analysis showed that reverse dipper (odds ratio [OR] 2.500; 95% confidence
      interval [CI] 1.320-4.736; P = 0.005), age (OR 1.089; 95% CI 1.067-1.111; P <
      0.001), smoke (OR 1.625; 95% CI 1.009-2.617; P = 0.046), and diabetes (OR 1.759;
      95% CI 1.093-2.830; P = 0.020) were significantly different between mild carotid
      plaque and normal. Our results also suggested that mild carotid plaque was
      closely related to reverse-dipper pattern of BP (2.308; 95% CI 1.223-4.355; P =
      0.010). Reverse-dipper pattern of BP may be a risk factor for carotid
      atherosclerosis and play a crucial role in the early formation of carotid plaque.

PMID- 25761181
TI  - Tracking nonpalpable breast cancer for breast-conserving surgery with carbon
      nanoparticles: implication in tumor location and lymph node dissection.
AB  - To examine the feasibility of using carbon nanoparticles to track nonpalpable
      breast cancer for breast-conserving surgery. During breast-conserving surgery, it
      is often very challenging to determine the boundary of tumor and identify
      involved lymph nodes. Currently used methods are useful in identifying tumor
      location, but do not provide direct visual guidance for resection margin during
      surgery. The study was approved by the Institutional Review Board of the Fuzhou
      General Hospital (Fuzhou, China). The current retrospective analysis included 16
      patients with nonpalpable breast cancer receiving breast-conserving surgery under
      the guidance of preoperative marking using a carbon nanoparticle, as well as 3
      patients receiving carbon nanoparticle marking followed by neoadjuvant treatment
      and then breast-conserving surgery. The Tumor Node Metastasis stage in the 16
      cases included: T1N0M0 in 7, T1N1M0 in 2, T2N0M0 in 4, and T2N1M0 in the
      remaining 3 cases. The nanoparticle was injected at 12 sites at 0.5 cm away from
      the apparent edge under colored ultrasonography along 6 tracks separated by 60
      degrees (2 sites every track). Lymph node status was also examined. The resection
      edge was free from cancer cells in all 16 cases (and the 3 cases with neoadjuvant
      treatment). Cancer cells were identified in majority of stained lymph nodes, but
      not in any of the unstained lymph nodes. No recurrence or metastasis was noticed
      after the surgery (2 to 22-month follow-up; median: 6 months). Tracking
      nonpalpable breast cancer with carbon nanoparticle could guide breast-conserving
      surgery.

PMID- 25761182
TI  - Markers of inflammation and mortality in a cohort of patients with alcohol
      dependence.
AB  - Inflammation and intestinal permeability are believed to be paramount features in
      the development of alcohol-related liver damage. We aimed to assess the impact of
      3 surrogate markers of inflammation (anemia, fibrinogen, and ferritin levels) on
      mid-term mortality of patients with alcohol dependence. This longitudinal study
      included patients with alcohol dependence admitted for hospital detoxification
      between 2000 and 2010. Mortality was ascertained from clinical charts and the
      mortality register. Associations between markers of inflammation and all-cause
      mortality were analyzed with mortality rates and Cox proportional hazards
      regression models. We also performed a subgroup analysis of mortality rates in
      patients with anemia, based on their mean corpuscular volume (MCV). We included
      909 consecutive patients with alcohol dependence. Patients were mostly male
      (80.3%), had a median age of 44 years (interquartile range [IQR]: 38-50), and
      upon admission, their median alcohol consumption was 192 g/day (IQR: 120-265). At
      admission, 182 (20.5%) patients had anemia; 210 (25.9%) had fibrinogen levels
      >4.5 mg/dL; and 365 (49.5%) had ferritin levels >200 ng/mL. At the end of follow
      up (median 3.8 years [IQR: 1.8-6.5], and a total of 3861.07 person-years), 118
      patients had died (12.9% of the study population). Cox regression models showed
      that the presence of anemia at baseline was associated with mortality (hazard
      ratio [HR]: 1.67, 95% confidence interval [CI]: 1.11-2.52, P < 0.01); no
      associations were found between mortality and high fibrinogen or high ferritin
      levels. A subgroup of patients with anemia was analyzed and compared to a control
      group of patients without anemia and a normal MCV. The mortality ratios of
      patients with normocytic and macrocytic anemia were 3.25 (95% CI: 1.41-7.26; P <
      0.01) and 3.39 (95% CI: 1.86-6.43; P < 0.01), respectively. Patients with alcohol
      dependence admitted for detoxification had an increased risk of death when anemia
      was present at admission. More accurate markers of systemic inflammation are
      needed to serve as prognostic factors for poor outcomes in this subset of
      patients.

PMID- 25761183
TI  - The prevalence and factors associated with hearing impairment in the Korean
      adults: the 2010-2012 Korea National Health and Nutrition Examination Survey
      (observational study).
AB  - There are few studies that have used audiometric testing to gauge the demographic
      characteristics and associated risk factors for hearing loss at the national
      level. Here, we investigated the weighted prevalence and associated factors of
      hearing impairment in 16,040 Korean adult population. Subjects completed
      audiometric test and laboratory examination as part of the data from The 2010
      2012 Korea National Health and Nutrition Examination Survey (KNHANES). In our
      respective study, the overall weighted (n = 33,762,584) prevalence of mild
      hearing impairment among the Korean adult population was 20.5% (95% clearance
      [CI], 19.6-21.6), whereas moderate-to-profound hearing impairment was 9.2% (95%
      CI, 8.6-9.9). The weighted prevalence of mild hearing impairment in younger
      adults (19-39 years' old) was 4.4% (3.5-5.5), in middle-age adults (40-64 years),
      it was 21.1% (19.8-22.5), and in older adults (>=65 years' old), it was 69.7%
      (67.8-71.6). Logistic regression analyses were performed for low/mid frequency or
      high-frequency mild hearing impairment with age, sex, tobacco use, heavy alcohol
      use, educational background, occupational noise exposure, obesity, hypertension,
      diabetes, total serum cholesterol, and estimated glomerular filtration rate
      (eGFR) <60 mL/min/1.73m2 as covariates. The analyses revealed independent
      correlations between increased age, tobacco use, education, hypertension, and
      eGFR <60 mL/min/1.73m2, and low/mid frequency and high frequency mild hearing
      impairment. High frequency mild hearing impairment was positively correlated with
      male sex, diabetes, and an increase in total serum cholesterol. Taken together,
      hearing impairment in Korea is highly prevalent with approximately one-fifth of
      Korean adult reporting mild hearing impairment. This study suggests that
      individuals with cardiovascular risk factors such as hypertension, diabetes,
      smoking, increased serum cholesterol, or decreased eGFR are at particular risk of
      developing hearing impairment. As such, these groups may benefit from hearing
      loss screening in addition to those groups typically considered to be of elevated
      risk including geriatrics, those of low socioeconomic status, and those with
      considerable occupational noise exposure.

PMID- 25761184
TI  - Red blood cell distribution width levels correlate with liver fibrosis and
      inflammation: a noninvasive serum marker panel to predict the severity of
      fibrosis and inflammation in patients with hepatitis B.
AB  - We aimed to study whether red blood cell distribution width (RDW) could be one of
      the variables determining the extent of liver fibrosis and inflammation in
      patients with biopsy-proven hepatitis B. A total of 446 hepatitis B virus
      infected patients who underwent liver biopsy were divided into 2 groups: absent
      or mild and moderate-severe according to the severity of liver fibrosis and
      inflammation. The independent variables that determine the severity of liver
      fibrosis and inflammation were explored. RDW values increased with progressive
      liver fibrosis and inflammation. After adjustments for other potent predictors,
      liver fibrosis (moderate-severe) was independently associated with RDW, platelet,
      and albumin (odds ratio = 1.121, 0.987, and 0.941, respectively), whereas
      increased odds ratios of significant inflammation were found for RDW, alanine
      aminotransferase, albumin, and PLT (odds ratio = 1.146, 1.003, 0.927, and 0.990,
      respectively). The sensitivity and specificity of model A were 70.0% and 62.9%
      for detection of significant liver fibrosis [area under the receiver-operating
      characteristic curve (AUC) = 0.713, P < 0.001]. The sensitivity and specificity
      of model B were 66.1% and 79.4% for predicting advanced liver inflammation (AUC =
      0.765, P < 0.001). Compared with preexisting indicators, model A achieved the
      highest AUC, whereas model B showed a higher AUC than RDW to platelet ratio
      (0.670, P < 0.001) and FIB-4 (0.740, P = 0.32). RDW may provide a useful clinical
      value for predicting liver fibrosis and necroinflammation in hepatitis B-infected
      patients with other markers.

PMID- 25761185
TI  - IL12p40 regulates functional development of human CD4+ T cells: enlightenment by
      the elevated expressions of IL12p40 in patients with inflammatory bowel diseases.
AB  - The proinflammatory effects of IL12p40 had been documented in the literature, and
      anti-IL12p40 treatment had been proved to be effective in therapy of Crohn
      disease (CD) in a phase 2b clinical trial. However, the precise role of IL12p40
      in the pathogenesis of inflammatory bowel disease (IBD) was still poorly
      understood. In this study, we investigated the expressions of IL12p40 and its
      receptor interleukin-12 receptor beta 1 both locally and systemically in IBD
      cases and healthy controls, and the contribution of IL12p40 in IBD pathogenesis.
      We found that the expression of IL12p40 was elevated both at messenger RNA and
      protein levels systematically and locally in IBD patients but more significantly
      in CD patients. Our genetic association study revealed that the polymorphisms of
      IL12B rs6887695 were associated with both CD and ulcerative colitis (UC)
      susceptibility in Chinese population, but did not affect the serum IL12p40 level
      in either CD patients or UC patients. In addition, CD4+ T cells isolated from
      peripheral blood of CD patients secreted the most abundant IL12p40 production,
      compared with the UC patients and healthy controls. We also found for the first
      time that neutralizing IL12p40 secretion could inhibit proliferation, enhance
      apoptosis, induce a G0/G1 arrest, restrain T helper 1 type immune responses, and
      promote chemokine C-C motif ligand 20-mediated migration of human CD4+ T cells,
      which might be the mechanisms why anti-IL12p40 treatment presented efficacy in
      CD.

PMID- 25761187
TI  - Risk for irritable bowel syndrome in fibromyalgia patients: a national database
      study.
AB  - Various studies have shown that irritable bowel syndrome (IBS) is highly
      associated with other pathologies, including fibromyalgia (FM). The objective of
      this study was to analyze the differences among risk factors associated with IBS
      following FM in a nationwide prospective cohort study. We propose that a
      relationship exists between FM and IBS. This article presents evidence obtained
      from a cohort study in which we used data from the Taiwan National Health
      Insurance Research Database to clarify the relationship between FM and IBS. The
      follow-up period ran from the start of FM diagnosis to the date of the IBS event,
      censoring, or December 31, 2011. We analyzed the risk of IBS using Cox
      proportional hazard regression models, including sex, age, and comorbidities.
      During the follow-up period, from 2000 to 2011, the overall incidence of IBS was
      higher in FM patients than in non-FM patients (7.47 vs 4.42 per 1000 person
      years), with a crude hazard ratio = 1.69 (95% confidence interval [CI] 1.45
      1.63). After adjustment for age, sex, and comorbidities, FM was associated with a
      1.54-fold increased risk for IBS. Mutually risk factors may influence the
      relationship between FM and IBS. We recommend that physiologists conduct annual
      examinations of FM patients to reduce the incidence of IBS progression.

PMID- 25761186
TI  - Plasma aldosterone concentration is positively associated with pulse pressure in
      patients with primary hypertension.
AB  - Increasing evidence showed a link between arterial elasticity and stiffness and
      pulse pressure (PP), in which plasma aldosterone may play a role. The
      observational study aimed to explore the potential relations between plasma
      aldosterone concentration (PAC) and PP in patients with hypertension. We
      evaluated the relation between PP and PAC in supine, seated, and upright
      positions in 195 patients with primary hypertension who underwent postural
      stimulation test. They were divided into 3 groups by tertiles of PP: PP <= 44 mm
      Hg (n = 70), 44 mm Hg < PP <= 51 mm Hg (n = 63), and PP >= 51 mm Hg (n = 62). The
      PAC in different postures was compared, respectively. The results showed the
      following. First, segregated by tertiles of PP, serum K+, 24-hour systolic blood
      pressure, 24-hour diastolic blood pressure, sex, upright PAC, and seated PAC
      showed statistically significant differences in groups. Second, the PAC were
      significantly different in 3 levels of PP regardless of postures, the individuals
      with PP >= 51 mm Hg had the highest PAC. On contrast, the patients with PAC > 12
      ng/dL showed greater PP than those with PAC <= 12 ng/dL. Third, weak associations
      between PP and upright (r = 0.288, P < 0.001), seated (r = 0.265, P < 0.001), and
      supine postures (r = 0.191, P = 0.008) were detected by simple correlation
      analysis. After corrected serum K+, age, and sex, the partial correlation
      coefficients did not change greatly. Fourth, the logistic regression model was
      constructed with PP >= 40 mm Hg or PP < 40 mm Hg as the dependent variable; the
      serum K+[OR = 0.043, 95% CI: 1.09(1.00-1.12)] and PAC [OR = 0.025, 95%CI:
      0.35(0.13-0.88)] were included as significant contributing factors. The results
      showed that higher PAC was weakly, but significantly, correlated to greater PP
      regardless of different postures, suggesting that higher PAC may be a risk factor
      of reduced arterial elasticity in patients with hypertension.

PMID- 25761188
TI  - Cervical spondylosis and hypertension: a clinical study of 2 cases.
AB  - Cervical spondylosis and hypertension are all common diseases, but the
      relationship between them has never been studied. Patients with cervical
      spondylosis are often accompanied with vertigo. Anterior cervical discectomy and
      fusion is an effective method of treatment for cervical spondylosis with cervical
      vertigo that is unresponsive to conservative therapy. We report 2 patients of
      cervical spondylosis with concomitant cervical vertigo and hypertension who were
      treated successfully with anterior cervical discectomy and fusion. Stimulation of
      sympathetic nerve fibers in pathologically degenerative disc could produce
      sympathetic excitation, and induce a sympathetic reflex to cause cervical vertigo
      and hypertension. In addition, chronic neck pain could contribute to hypertension
      development through sympathetic arousal and failure of normal homeostatic pain
      regulatory mechanisms. Cervical spondylosis may be one of the causes of secondary
      hypertension. Early treatment for resolution of symptoms of cervical spondylosis
      may have a beneficial impact on cardiovascular disease risk in patients with
      cervical spondylosis.

PMID- 25761189
TI  - Triglyceride to high-density lipoprotein cholesterol ratio predicts
      cardiovascular outcomes in prevalent dialysis patients.
AB  - Triglyceride to high-density lipoprotein cholesterol (TG/HDL-C) ratio, an
      indicator of atherogenic dyslipidemia, is a predictor of cardiovascular (CV)
      outcomes in the general population and has been correlated with atherosclerotic
      events. Whether the TG/HDL-C ratio can predict CV outcomes and survival in
      dialysis patients is unknown. We performed this prospective, observational cohort
      study and enrolled 602 dialysis patients (539 hemodialysis and 63 peritoneal
      dialysis) from a single center in Taiwan followed up for a median of 3.9 years.
      The outcomes were the occurrence of CV events, CV death, and all-cause mortality
      during follow-up. The association of baseline TG/HDL-C ratio with outcomes was
      explored with Cox regression models, which were adjusted for demographic
      parameters and inflammatory/nutritional markers. Overall, 203 of the patients
      experienced CV events and 169 patients died, of whom 104 died due to CV events.
      Two hundred fifty-four patients reached the composite CV outcome. Patients with
      higher TG/HDL-C levels (quintile 5) had a higher incidence of CV events (adjusted
      hazard ratio [HR] 2.03, 95% confidence interval [CI] 1.19-3.47), CV mortality
      (adjusted HR 1.91, 95% CI 1.07-3.99), composite CV outcome (adjusted HR 2.2, 95%
      CI 1.37-3.55), and all-cause mortality (adjusted HR 1.94, 95% CI 1.1-3.39)
      compared with the patients in quintile 1. However, in diabetic dialysis patients,
      the TG/HDL-C ratio did not predict the outcomes. The TG/HDL-C ratio is a reliable
      and easily accessible predictor to evaluate CV outcomes and survival in prevalent
      nondiabetic dialysis patients. ClinicalTrials.gov: NCT01457625.

PMID- 25761190
TI  - Necessity of harvesting at least 25 lymph nodes in patients with stage N2-N3
      resectable gastric cancer: a 10-year, single-institution cohort study.
AB  - A minimum of 15 lymph nodes (LNs) has been recommended as an adequate number for
      radical gastrectomy for gastric cancer (GC). This study aimed to investigate
      whether the harvesting of at least 25 LNs was a better criterion for stage N2-3
      GC based on the 10-year experience of a high-volume hospital. A total of 1363
      patients who underwent radical gastrectomy for gastric cancer between 2000 and
      2010 were included in this study. The relationship between the number of lymph
      nodes examined during gastrectomy and overall survival (OS) was analyzed. In
      multivariate analysis, the numbers of LNs examined (P = 0.001) and N stage were
      confirmed as 2 of the independent prognostic factors. A larger proportion of
      N2/N3a/N3b patients was observed in the group with >=20 LNs examined. The cutoff
      of >=25 LNs examined exhibited a significantly lower hazard ratio (HR) than other
      LN cutoffs among N2-N3 diseases, but the cutoff was not significantly superior to
      other cutoffs in patients with N0 and N1 disease (HR, 0.64, 0.62, and 0.53 for
      N2, N3a, and N3b, respectively). The 5-year OS rates were 58.59% and 32.77% for
      N2 and N3 diseases, respectively, with >=25 LNs examined, which represents a
      significant improvement over 15-24 LNs examined (52.48% and 21.67% for N2 and N3
      stages, respectively). Among patients with stage N2-N3 GC, harvesting at least 25
      LNs may represent a superior cutoff for radical gastrectomy and could yield
      better survival outcomes.

PMID- 25761191
TI  - Carbon monoxide poisoning and subsequent cardiovascular disease risk: a
      nationwide population-based cohort study.
AB  - Carbon monoxide (CO) poisoning is considered one of the most crucial health
      concerns. Few studies have investigated the correlation between CO poisoning and
      the risk of developing cardiovascular diseases (CVDs). Therefore, we conducted a
      population-based, longitudinal cohort study in Taiwan to determine whether
      patients with CO poisoning are associated with higher risk of developing
      subsequent CVDs, including arrhythmia, coronary artery disease (CAD) and
      congestive heart failure (CHF). This retrospective study used the National Health
      Insurance Research Database. The study cohort comprised all patients aged >=20
      years with a diagnosis of CO poisoning and hospitalized during 2000 to 2011 (N =
      8381), and the comparison cohort comprised randomly selected non-CO-poisoned
      patients (N = 33,524) frequency-matched with the study cohort by age, sex, and
      the year of index date. Each patient was individually tracked to identify those
      who develop CVD events during the follow-up period. Cox proportional hazards
      regression model was performed to calculate the hazard ratios of CVDs after
      adjusting for possible confounders. The overall incidences of arrhythmia, CAD,
      and CHF were higher in the patients with CO poisoning than in the controls (2.57
      vs 1.25/1000 person-years, 3.28 vs 2.25/1000 person-years, and 1.32 vs 1.05/1000
      person-years, respectively). After adjusting for age, sex, and comorbidities, the
      patients with CO poisoning were associated with a 1.83-fold higher risk of
      arrhythmia compared with the comparison cohort, and nonsignificantly associated
      with risk of CAD and CHF. CO-poisoned patients with coexisting comorbidity or in
      high severity were associated with significantly and substantially increased risk
      of all 3 CVDs. CO poisoning is associated with increased risk of subsequent
      development of arrhythmia. Future studies are required to explore the long-term
      effects of CO poisoning on the cardiovascular system.

PMID- 25761192
TI  - Type D personality parents of children with leukemia tend to experience anxiety:
      the mediating effects of social support and coping style.
AB  - The aims were to access anxiety and type D personality (TDP) in parents of
      children with leukemia, and to determine the mediating effect of social support
      and coping style on the relationship between TDP and anxiety. A cross-sectional
      study was conducted among 231 parents of children with leukemia and 261 parents
      of children with acute diseases in hospitals. Parents completed questionnaires on
      anxiety, TDP, social support, coping styles, children's clinical characteristics,
      and demographic characteristics. Parents of children with leukemia showed higher
      prevalence of anxiety (64.5% vs 40.2%, P < 0.01) and TDP (44.2% vs 24.1%, P <
      0.01) compared with controls. TDP (odds ratio [OR] = 4.34, P < 0.01), lower
      social support (OR = 1.92, P = 0.02), and less positive coping (OR = 1.87, P =
      0.02) were independently associated with anxiety. Parents with TDP showed lower
      social support and less positive coping, but more negative coping compared with
      those without. Moreover, multiple mediation analyses revealed that the
      significant effect of TDP on anxiety was partially mediated by social support and
      positive coping. In conclusion, anxiety and TDP were highly prevalent in parents
      of children with leukemia. The predictive factors could be used to identify those
      parents who are at high risk of anxiety and may also be targets for prevention
      and intervention.

PMID- 25761193
TI  - The risk of depression in patients with cholelithiasis before and after
      cholecystectomy: a population-based cohort study.
AB  - The association between cholelithiasis and depression remains unclear. We
      examined the risk of depression in patients with cholelithiasis. From the
      National Health Insurance population claims data of Taiwan, we identified 14071
      newly diagnosed cholelithiasis patients (4969 symptomatic and 9102 asymptomatic)
      from 2000 to 2010. For each cholelithiasis patient, 4 persons without
      cholelithiasis were randomly selected in the control cohort from the general
      population frequency matched by age, sex, and diagnosis year. Both cohorts were
      followed up until the end of 2011 to monitor the occurrence of depression.
      Adjusted hazard ratios (aHRs) of depression were estimated using the Cox
      proportional hazards model after controlling for age, sex and comorbidities. The
      overall incidence rates of depression were 1.87- and 1.83-fold greater in the
      symptomatic and asymptomatic cholelithiasis subcohorts than in the control cohort
      (incidence, 10.1 and 9.96 vs 5.43 per 1000 person-years, respectively). The
      multivariable Cox proportional hazards regression analysis revealed higher
      variable-specific aHRs in women than in men, in younger patients than in older
      patients, and in those without comorbidities than in those with any comorbidity.
      Cholecystectomy reduced the hazard of developing depression with aHRs of 0.79
      (95% confidence interval [CI] 0.62-0.99) for symptomatic cholelithiasis patients
      and 0.76 (95% CI 0.60-0.96) for asymptomatic patients. Patients with
      cholelithiasis are at a higher risk of developing depression than the general
      population. Patients could be benefited from cholecystectomy and have the hazard
      of developing depression significantly reduced.

PMID- 25761194
TI  - Delayed sudden radial artery rupture after left transradial coronary
      catheterization: a case report.
AB  - Local complications at the radial access site are not frequent, hence its large
      diffusion as the preferred access route for endovascular procedures. However, in
      a time of fast widespreading, better comprehension of all potential complications
      becomes critical to facilitate their early recognition and the most appropriate
      treatment. In this case report, we present for the first time a case of sudden
      massive bleeding at the left wrist, due to spontaneous gross rupture of the left
      radial artery bleeding 15 days after an endovascular procedure through a left
      radial arterial access. The patient had been readmitted to the hospital after
      evidence of local infection at the left wrist with loss of substance. The radial
      artery was patent with no evidence of pseudoaneurysm. After sudden radial artery
      rupture, with massive bleeding and suspicion that the local infection could have
      reached the arterial wall, surgical hemostasis with artery ligation was obtained.
      Healing of the large wound was then efficiently speeded up using a negative
      pressure wound therapy. This is the first case of macroscopic radial artery
      rupture associated with local wrist infection after arterial catheterization.
      After prompt surgical hemostasis, negative pressure wound therapy was very
      helpful in favoring healing of the large and deep wound.

PMID- 25761196
TI  - ERPA-APSG: a computationally efficient geminal-based method for accurate
      description of chemical systems.
AB  - Most computational chemistry methods cannot provide a uniformly accurate
      description of dynamic and static electron correlation. In this paper we present
      the performance of the ERPA-APSG method based on the antisymmetrized product of
      strongly orthogonal geminal theory (APSG) and the recently proposed extended
      random phase approximation (ERPA) intergeminal correlation correction. We show
      that the ERPA-APSG approach is capable of accounting for both dynamic and static
      correlation, yielding excellent results when applied to describing conformational
      changes in molecules, twisting of the ethylene molecule, and deprotonation
      reactions. 

PMID- 25761197
TI  - Unraveling ultrafast photoinduced proton transfer dynamics in a fluorescent
      protein biosensor for Ca(2+) imaging.
AB  - Imaging Ca(2+) dynamics in living systems holds great potential to advance
      neuroscience and cellular biology. G-GECO1.1 is an intensiometric fluorescent
      protein Ca(2+) biosensor with a Thr-Tyr-Gly chromophore. The protonated
      chromophore emits green upon photoexcitation via excited-state proton transfer
      (ESPT). Upon Ca(2+) binding, a significant population of the chromophores becomes
      deprotonated. It remains elusive how the chromophore structurally evolves prior
      to and during ESPT, and how it is affected by Ca(2+) . We use femtosecond
      stimulated Raman spectroscopy to dissect ESPT in both the Ca(2+) -free and bound
      states. The protein chromophores exhibit a sub-200 fs vibrational frequency shift
      due to coherent small-scale proton motions. After wavepackets move out of the
      Franck-Condon region, ESPT gets faster in the Ca(2+) -bound protein, indicative
      of the formation of a more hydrophilic environment. These results reveal the
      governing structure-function relationship of Ca(2+) -sensing protein biosensors.

PMID- 25761198
TI  - The inhibitory effects of Geranium thunbergii on interferon-gamma- and LPS
      induced inflammatory responses are mediated by Nrf2 activation.
AB  - Geranium thunbergii Sieb. et Zucc. (GT; which belongs to the Geraniaceae family)
      has been used as a traditional medicine in East Asia for the treatment of
      inflammatory diseases, including arthritis and diarrhea. However, the underlying
      mechanisms of the anti-inflammatory effects of GT remain poorly understood. In
      the present study, we examined the mechanisms responsible for the anti
      inflammatory activity of GT in macrophages. The results revealed that GT
      significantly inhibited the lipopolysaccharide (LPS)- and interferon-gamma (IFN
      gamma)-induced expression of pro-inflammatory genes, such as inducible nitric
      oxide synthase, tumor necrosis factor-alpha and interleukin-1beta, as shown by RT
      PCR. However, the inhibitory effects of GT on LPS- and IFN-gamma-induced
      inflammation were associated with an enhanced nuclear factor erythroid 2-related
      factor 2 (Nrf2) activity, but not with the suppression of nuclear factor (NF)
      kappaB activity, as shown by western blot analysis. In addition, in bone marrow
      derived macrophages (BMDM) isolated from Nrf2 knockout mice, GT did not exert any
      inhibitory effect on the LPS- and IFN-gamma-induced inflammation. Taken together,
      our findings indicate that the anti-inflammatory effects of GT may be associated
      with the activation of Nrf2, an anti-inflammatory transcription factor.

PMID- 25761200
TI  - Differences in activation of aryl hydrocarbon receptors of white sturgeon
      relative to lake sturgeon are predicted by identities of key amino acids in the
      ligand binding domain.
AB  - Dioxin-like compounds (DLCs) are pollutants of global environmental concern. DLCs
      elicit their adverse outcomes through activation of the aryl hydrocarbon receptor
      (AhR). However, there is limited understanding of the mechanisms that result in
      differences in sensitivity to DLCs among different species of fishes.
      Understanding these mechanisms is critical for protection of the diversity of
      fishes exposed to DLCs, including endangered species. This study investigated
      specific mechanisms that drive responses of two endangered fishes, white sturgeon
      (Acipenser transmontanus) and lake sturgeon (Acipenser fulvescens) to DLCs. It
      determined whether differences in sensitivity to activation of AhRs (AhR1 and
      AhR2) can be predicted based on identities of key amino acids in the ligand
      binding domain (LBD). White sturgeon were 3- to 30-fold more sensitive than lake
      sturgeon to exposure to 5 different DLCs based on activation of AhR2. There were
      no differences in sensitivity between white sturgeon and lake sturgeon based on
      activation of AhR1. Adverse outcomes as a result of exposure to DLCs have been
      shown to be mediated through activation of AhR2, but not AhR1, in all fishes
      studied to date. This indicates that white sturgeon are likely to have greater
      sensitivity in vivo relative to lake sturgeon. Homology modeling and in silico
      mutagenesis suggests that differences in sensitivity to activation of AhR2 result
      from differences in key amino acids at position 388 in the LBD of AhR2 of white
      sturgeon (Ala-388) and lake sturgeon (Thr-388). This indicates that identities of
      key amino acids in the LBD of AhR2 could be predictive of both in vitro
      activation by DLCs and in vivo sensitivity to DLCs in these, and potentially
      other, fishes. 

PMID- 25761201
TI  - Using satellite multispectral imagery for damage mapping of armyworm (Spodoptera
      frugiperda) in maize at a regional scale.
AB  - BACKGROUND: Armyworm, a destructive insect for maize, has caused a wide range of
      damage in both China and the United States in recent years. To obtain the spatial
      distribution of the damage area, and to assess the damage severity, a fast and
      accurate loss assessment method is of great importance for effective
      administration. The objectives of this study were to determine suitable spectral
      features for armyworm detection and to develop a mapping method at a regional
      scale on the basis of satellite remote sensing image data. RESULTS: Armyworm
      infestation can cause a significant change in the plant's leaf area index, which
      serves as a basis for infestation monitoring. Among the number of vegetation
      indices that were examined for their sensitivity to insect damage, the modified
      soil-adjusted vegetation index was identified as the optimal vegetation index for
      detecting armyworm. A univariate model relying on two-date satellite images
      significantly outperformed a multivariate model, with the overall accuracy
      increased from 0.50 to 0.79. CONCLUSION: A mapping method for monitoring armyworm
      infestation at a regional scale has been developed, based on a univariate model
      and two-date multispectral satellite images. The successful application of this
      method in a typical armyworm outbreak event in Tangshan, Hebei Province, China,
      demonstrated the feasibility of the method and its promising potential for
      implementation in practice.

PMID- 25761203
TI  - Biomechanical study of ACL reconstruction grafts.
AB  - There are no published studies describing the strength quadrupled gracilis tendon
      alone and quadrupled semitendinosus tendon alone in the configuration used for
      anterior cruciate ligament (ACL) reconstruction. The primary objective was to
      compare the mechanical properties of grafts used for ACL reconstruction during a
      tensile failure test. The secondary objective was to evaluate the effect of
      uniform suturing on graft strength. Fifteen pairs of knees were used. The
      mechanical properties of five types of ACL grafts were evaluated: patellar tendon
      (PT), sutured patellar tendon (sPT), both hamstring tendons (GST4), quadrupled
      semitendinosus (ST4), and quadrupled gracilis (G4). Validated methods were used
      to perform the tensile tests to failure and to record the results. Student's t
      test was used to compare the various samples. The maximum load to failure was
      630.8N (+/- 239.1) for the ST4, 473.5N (+/- 176.9) for the GST4, 413.3N (+/-
      120.4) for the sPT, and 416.4N (+/- 187.7) for the G4 construct. Only the ST4 had
      a significantly higher failure load than the other grafts. The sPT had a higher
      failure load than the PT. The ST4 construct had the highest maximum load to
      failure of all the ACL graft types in the testing performed here. Uniform
      suturing of the grafts improved their ability to withstand tensile loading.

PMID- 25761202
TI  - Factors associated with nocturnal hypoglycemia in at-risk adolescents and young
      adults with type 1 diabetes.
AB  - BACKGROUND: Hypoglycemia remains an impediment to good glycemic control, with
      nocturnal hypoglycemia being particularly dangerous. Information on major
      contributors to nocturnal hypoglycemia remains critical for understanding and
      mitigating risk. MATERIALS AND METHODS: Continuous glucose monitoring (CGM) data
      for 855 nights were studied, generated by 45 subjects 15-45 years of age with
      hemoglobin A1c (HbA1c) levels of <=8.0% who participated in a larger randomized
      study. Factors assessed for potential association with nocturnal hypoglycemia
      (CGM measurement of <60 mg/dL for >=30 min) included bedtime blood glucose (BG),
      exercise intensity, bedtime snack, insulin on board, day of the week, previous
      daytime hypoglycemia, age, gender, HbA1c level, diabetes duration, daily basal
      insulin, and daily insulin dose. RESULTS: Hypoglycemia occurred during 221 of 885
      (25%) nights and was more frequent with younger age (P<0.001), lower HbA1c levels
      (P=0.006), medium/high-intensity exercise during the preceding day (P=0.003), and
      the occurrence of antecedent daytime hypoglycemia (P=0.001). There was a trend
      for lower bedtime BG levels to be associated with more frequent nocturnal
      hypoglycemia (P=0.10). Bedtime snack, before bedtime insulin bolus, weekend
      versus weekday, gender, and daily basal and bolus insulin were not associated
      with nocturnal hypoglycemia. CONCLUSIONS: Awareness that HbA1c level, exercise,
      bedtime BG level, and daytime hypoglycemia are all modifiable factors associated
      with nocturnal hypoglycemia may help patients and providers decrease the risk of
      hypoglycemia at night. Risk for nocturnal hypoglycemia increased in a linear
      fashion across the range of variables, with no clear-cut thresholds to guide
      clinicians or patients for any particular night.

PMID- 25761204
TI  - Facile synthesis of fluorescent polymer nanoparticles by covalent modification
      nanoprecipitation of amine-reactive ester polymers.
AB  - Emission wavelength control in fluorescent nanoparticles (NPs) is crucial for
      their applications. In the case of inorganic quantum dots or dye-impregnated
      silica NPs, such a control is readily achieved by changing the size of the
      particles or choosing appropriate fluorescent dyes, respectively. A similar
      modular approach for controlling the emission wavelength of fluo-rescent polymer
      NPs, however, is difficult. This article reports on fluorescent polymer NPs, the
      synthesis of which provides a platform for a modular approach towards the
      preparation of fluorescent NPs of desired emission wavelength. Atom-transfer
      radical polymerization (ATRP) is employed to synthesize reactive ester polymers,
      which are then easily modified with a commercially available dye and subsequently
      subjected to nanoprecipitation. The resulting NPs, with low size polydispersity,
      show an enhanced emission quantum yield when compared with the same dye molecules
      in solution.

PMID- 25761205
TI  - 'Hyperaldosteronaemic or normocalcaemic' hyperparathyroidism?

PMID- 25761206
TI  - A new cytotoxic benzophenanthridine isoquinoline alkaloid from the fruits of
      Macleaya cordata.
AB  - A new cytotoxic benzophenanthridine isoquinoline alkaloid, named cordatine (1),
      together with one known alkaloid 8-methoxydihydrochelerythrine (2), was isolated
      from the fruits of Macleaya cordata. The structure of the new compound was
      elucidated by spectroscopic methods including 1D and 2D NMR, HR-ESI-MS. Both
      compounds indicated significant cytotoxicity against MCF-7 and SF-268 cell lines.

PMID- 25761207
TI  - A Lotus japonicus Cochaperone Protein Interacts With the Ubiquitin-Like Domain
      Protein CIP73 and Plays a Negative Regulatory Role in Nodulation.
AB  - The calcium/calmodulin-dependent protein kinase CCaMK forms a complex with its
      phosphorylation target CIP73 (CCaMK-interacting protein of 73 kDa). In this work,
      a homolog of the animal HSC/HSP70 interacting protein (HIP) was identified as an
      interacting partner of CIP73 in Lotus japonicus. L. japonicus HIP contains all
      functional domains characteristic of animal HIP proteins. The C-terminal STI1
      like domain of L. japonicus HIP was found to be necessary and sufficient for
      interaction with CIP73. The interaction between CIP73 and HIP occurred in both
      the nuclei and cytoplasm in Nicotiana benthamiana leaf cells. The interactions
      between CIP73 and HIP and between CIP73 and CCaMK could take place simultaneously
      in the same nuclei. HIP transcripts were detected in all plant tissues tested. As
      nodule primordia developed into young nodules, the expression of HIP was down
      regulated and the HIP transcript level became very low in mature nodules. More
      nodules were formed in transgenic hairy roots of L. japonicus expressing HIP RNA
      interference at 16 days postinoculation as compared with the control hairy roots
      expressing the empty vector. It appears that HIP may play a role as a negative
      regulator for nodulation. 

PMID- 25761208
TI  - The Novel Lipopeptide Poaeamide of the Endophyte Pseudomonas poae RE*1-1-14 Is
      Involved in Pathogen Suppression and Root Colonization.
AB  - Endophytic Pseudomonas poae strain RE*1-1-14 was originally isolated from
      internal root tissue of sugar beet plants and shown to suppress growth of the
      fungal pathogen Rhizoctonia solani both in vitro and in the field. To identify
      genes involved in its biocontrol activity, RE*1-1-14 random mutagenesis and
      sequencing led to the identification of a nonribosomal peptide synthetase (NRPS)
      gene cluster predicted to encode a lipopeptide (LP) with a 10-amino-acid peptide
      moiety. The two unlinked gene clusters consisted of three NRPS genes, designated
      poaA (cluster 1) and poaB and poaC (cluster 2), spanning approximately 33.7 kb.
      In silico analysis followed by chemical analyses revealed that the encoded LP,
      designated poaeamide, is a structurally new member of the orfamide family.
      Poaeamide inhibited mycelial growth of R. solani and different oomycetes,
      including Phytophthora capsici, P. infestans, and Pythium ultimum. The novel LP
      was shown to be essential for swarming motility of strain RE*1-1-14 and had an
      impact on root colonization of sugar beet seedlings The poaeamide-deficient
      mutant colonized the rhizosphere and upper plant cortex at higher densities and
      with more scattered colonization patterns than the wild type. Collectively, these
      results indicate that Pseudomonas poae RE*1-1-14 produces a structurally new LP
      that is relevant for its antagonistic activity against soilborne plant pathogens
      and for colonization of sugar beet roots. 

PMID- 25761209
TI  - Fluorescently Tagged Potato virus Y: A Versatile Tool for Functional Analysis of
      Plant-Virus Interactions.
AB  - Potato virus Y (PVY) is an economically important plant virus that infects
      Solanaceous crops such as tobacco and potato. To date, studies into the
      localization and movement of PVY in plants have been limited to detection of
      viral RNA or proteins ex vivo. Here, a PVY N605 isolate was tagged with green
      fluorescent protein (GFP), characterized and used for in vivo tracking. In
      Nicotiana tabacum cv. Xanthi, PVY N605-GFP was biologically comparable to
      nontagged PVY N605, stable through three plant-to-plant passages and persisted
      for four months in infected plants. GFP was detected before symptoms and
      fluorescence intensity correlated with PVY RNA concentrations. PVY N605-GFP
      provided in vivo tracking of long-distance movement, allowing estimation of the
      cell-to-cell movement rate of PVY in N. tabacum cv. Xanthi (7.1 +/- 1.5 cells per
      hour). PVY N605-GFP was adequately stable in Solanum tuberosum cvs. Desiree and
      NahG-Desiree and able to infect S. tuberosum cvs. Bintje and Bea, Nicotiana
      benthamiana, and wild potato relatives. PVY N605-GFP is therefore a powerful tool
      for future studies of PVY-host interactions, such as functional analysis of viral
      and plant genes involved in viral movement. 

PMID- 25761210
TI  - QTL Analysis for Resistance to Blast Disease in U.S. Weedy Rice.
AB  - Understanding the genetic architecture of adaptation is of great importance in
      evolutionary biology. U.S. weedy rice is well adapted to the local conditions in
      U.S. rice fields. Rice blast disease is one of the most destructive diseases of
      cultivated rice worldwide. However, information about resistance to blast in
      weedy rice is limited. Here, we evaluated the disease reactions of 60 U.S. weedy
      rice accessions with 14 blast races, and investigated the quantitative trait loci
      (QTL) associated with blast resistance in two major ecotypes of U.S. weedy rice.
      Our results revealed that U.S. weedy rice exhibited a broad resistance spectrum.
      Using genotyping by sequencing, we identified 28 resistance QTL in two U.S. weedy
      rice ecotypes. The resistance QTL with relatively large and small effects suggest
      that U.S. weedy rice groups have adapted to blast disease using two methods, both
      major resistance (R) genes and QTL. Three genomic loci shared by some of the
      resistance QTL indicated that these loci may contribute to no-race-specific
      resistance in weedy rice. Comparing with known blast disease R genes, we found
      that the R genes at these resistance QTL are novel, suggesting that U.S. weedy
      rice is a potential source of novel blast R genes for resistant breeding. 

PMID- 25761211
TI  - Occupational radiation dose to eyes from interventional radiology procedures in
      light of the new eye lens dose limit from the International Commission on
      Radiological Protection.
AB  - OBJECTIVE: In 2011, the International Commission on Radiological Protection
      (ICRP) recommended a substantial reduction in the equivalent dose limit for the
      lens of the eye, in line with a reduced threshold of absorbed dose for radiation
      induced cataracts. This is of particular relevance in interventional radiology
      (IR) where it is well established that staff doses can be significant, however,
      there is a lack of data on IR eye doses in terms of Hp(3). Hp(3) is the personal
      dose equivalent at a depth of 3 mm in soft tissue and is used for measuring lens
      dose. We aimed to obtain a reliable estimate of eye dose to IR operators.
      METHODS: Lens doses were measured for four interventional radiologists over a 3
      month period using dosemeters specifically designed to measure Hp(3). RESULTS:
      Based on their typical workloads, two of the four interventional radiologists
      would exceed the new ICRP dose limit with annual estimated doses of 31 and 45 mSv
      to their left eye. These results are for an "unprotected" eye, and for IR staff
      who routinely wear lead glasses, the dose beneath the glasses is likely to be
      significantly lower. Staff eye dose normalized to patient kerma-area product and
      eye dose per procedure have been included in the analysis. CONCLUSION: Eye doses
      to IR operators have been established using a dedicated Hp(3) dosemeter.
      Estimated annual doses have the potential to exceed the new ICRP limit. ADVANCES
      IN KNOWLEDGE: We have estimated lens dose to interventional radiologists in terms
      of Hp(3) for the first time in an Irish hospital setting.

PMID- 25761212
TI  - A review of recent advances in optical fibre sensors for in vivo dosimetry during
      radiotherapy.
AB  - This article presents an overview of the recent developments and requirements in
      radiotherapy dosimetry, with particular emphasis on the development of optical
      fibre dosemeters for radiotherapy applications, focusing particularly on in vivo
      applications. Optical fibres offer considerable advantages over conventional
      techniques for radiotherapy dosimetry, owing to their small size, immunity to
      electromagnetic interferences, and suitability for remote monitoring and
      multiplexing. The small dimensions of optical fibre-based dosemeters, together
      with being lightweight and flexible, mean that they are minimally invasive and
      thus particularly suited to in vivo dosimetry. This means that the sensor can be
      placed directly inside a patient, for example, for brachytherapy treatments, the
      optical fibres could be placed in the tumour itself or into nearby critical
      tissues requiring monitoring, via the same applicators or needles used for the
      treatment delivery thereby providing real-time dosimetric information. The
      article outlines the principal sensor design systems along with some of the main
      strengths and weaknesses associated with the development of these techniques. The
      successful demonstration of these sensors in a range of different clinical
      environments is also presented. 

PMID- 25761213
TI  - Comparative dosimetry study of three UK centres implementing total skin electron
      treatment through external audit.
AB  - OBJECTIVE: This article describes the external audit measurements conducted in
      two UK centres implementing total skin electron beam therapy (TSEBT) and the
      results obtained. METHODS: Measurements of output, energy, beam flatness and
      symmetry at a standard distance (95 or 100 cm SSD) were performed using a
      parallel plate chamber in solid water. Similarly, output and energy measurements
      were also performed at the treatment plane for single and dual fields. Clinical
      simulations were carried out using thermoluminescent dosemeters (TLDs) and
      Gafchromic(r) film (International Specialty Products, Wayne, NJ) on an
      anthropomorphic phantom. RESULTS: Extended distance measurements confirmed that
      local values for the beam dosimetry at Centres A and B were within 2% for outputs
      and 1-mm agreement of the expected depth at which the dose is 50% of the maximum
      for the depth-dose curve in water (R50,D) value. Clinical simulation using TLDs)
      showed an agreement of -1.6% and -6.7% compared with the expected mean trunk dose
      for each centre, respectively, and a variation within 10% (+/-1 standard
      deviation) across the trunk. The film results confirmed that the delivery of the
      treatment technique at each audited centre complies with the European
      Organisation for Research and Treatment of Cancer recommendations. CONCLUSION:
      This audit methodology has proven to be a successful way to confirm the agreement
      of dosimetric parameters for TSEBT treatments at both audited centres and could
      serve as the basis for an audit template to be used by other audit groups.
      ADVANCES IN KNOWLEDGE: TSEBT audits are not established in the UK owing to a
      limited number of centres carrying out the treatment technique. This article
      describes the audits performed at two UK centres prior to their clinical
      implementation.

PMID- 25761214
TI  - Impact of utilizing a women-based formula for determining adequacy of the
      chronotropic response during exercise treadmill testing.
AB  - BACKGROUND: A women-based formula for calculation of age-predicted maximum heart
      rate [age-predicted maximum heart rate=206-(0.88*age)] was established in
      asymptomatic volunteer women undergoing treadmill exercise tolerance testing
      (ETT). We sought to perform a comparison of the performance of this women-based
      formula for prediction of peak heart rate to the traditional formula [220-age]
      and our own database-generated prediction formula in a large database of women
      undergoing ETT. METHODS: We performed a retrospective analysis of all consecutive
      women who underwent symptom-limited Bruce protocol ETT at the Mayo Clinic from
      1994 to 2010. Women with known cardiovascular disease or those using beta
      blockers, calcium channel blockers, or digitalis were excluded. Separate analyses
      were performed according to symptomatic status. RESULTS: The study included
      11,029 women (89.4% Caucasian) with a mean age 52+/-12 years; 3,632 (33%) were
      referred specifically for evaluation of symptoms. Age-predicted maximum heart
      rate calculated by the traditional formula was achieved by 49.7% of women versus
      69.9% by the women-based formula with most of the underestimation observed in
      older women. Average absolute deviation between achieved and predicted peak heart
      rate (HR) was 10.85+/-9.18 bpm for traditional versus 11.98+/-9.00 for women
      based formulas (dependent t=-16.64, p<0.0001). The linear regression line
      calculated from our population [HR=201-(0.67*age)] was closer to the women-based
      formula, both in terms of intercept and slope than the traditional formula. Peak
      HR was shown to be slightly affected (-2.5 bpm) by symptom status at referral,
      whereas smoking and diabetes more significantly reduced achieved peak HR.
      CONCLUSIONS: The women-based formula underestimated peak HR, especially in older
      women, but was observed to be closer in both intercept and slope to the
      regression line determined from our study in this large population of female
      patients. These sex-unique observations should be taken into account when
      determining adequacy and targets for ETT in women.

PMID- 25761215
TI  - Author's response to Nicolau et al.

PMID- 25761217
TI  - Novelties in secretory structures and anatomy of Rhynchosia (Fabaceae).
AB  - A comparative anatomical study was carried out on the secretory structures of
      leaflets from taxa belonging to the genus Rhynchosia - taxa difficult to delimit
      because of uncertain interspecific relations - in order to evaluate the potential
      diagnostic value of these anatomical traits for taxonomic assignment. A further
      objective was to establish consensual denomination for these secretory
      structures. The new anatomical features found in these taxa were sufficiently
      consistent to separate the species evaluated. The presence and localization of
      glandular-punctate structures bulbous-based trichomes, the number of layers in
      the palisade parenchyma and the arrangement of vascular units distinguish the
      taxa investigated and these characteristics can be extended to other species of
      Papilionoideae. The trichomes analyzed were described and classified into five
      types. Depicted in diagrams, photomicrographs, and by scanning electron
      microscopy, and listed for the first time at the genus and species levels. The
      information obtained served to effectively distinguish the taxa investigated
      among species of Papilonoideae. 

PMID- 25761216
TI  - The contribution of alu elements to mutagenic DNA double-strand break repair.
AB  - Alu elements make up the largest family of human mobile elements, numbering 1.1
      million copies and comprising 11% of the human genome. As a consequence of
      evolution and genetic drift, Alu elements of various sequence divergence exist
      throughout the human genome. Alu/Alu recombination has been shown to cause
      approximately 0.5% of new human genetic diseases and contribute to extensive
      genomic structural variation. To begin understanding the molecular mechanisms
      leading to these rearrangements in mammalian cells, we constructed Alu/Alu
      recombination reporter cell lines containing Alu elements ranging in sequence
      divergence from 0%-30% that allow detection of both Alu/Alu recombination and
      large non-homologous end joining (NHEJ) deletions that range from 1.0 to 1.9 kb
      in size. Introduction of as little as 0.7% sequence divergence between Alu
      elements resulted in a significant reduction in recombination, which indicates
      even small degrees of sequence divergence reduce the efficiency of homology
      directed DNA double-strand break (DSB) repair. Further reduction in recombination
      was observed in a sequence divergence-dependent manner for diverged Alu/Alu
      recombination constructs with up to 10% sequence divergence. With greater levels
      of sequence divergence (15%-30%), we observed a significant increase in DSB
      repair due to a shift from Alu/Alu recombination to variable-length NHEJ which
      removes sequence between the two Alu elements. This increase in NHEJ deletions
      depends on the presence of Alu sequence homeology (similar but not identical
      sequences). Analysis of recombination products revealed that Alu/Alu
      recombination junctions occur more frequently in the first 100 bp of the Alu
      element within our reporter assay, just as they do in genomic Alu/Alu
      recombination events. This is the first extensive study characterizing the
      influence of Alu element sequence divergence on DNA repair, which will inform
      predictions regarding the effect of Alu element sequence divergence on both the
      rate and nature of DNA repair events. 

PMID- 25761218
TI  - Biological associations of color variation in the Indo-Pacific swimming crab
      Charybdis hellerii.
AB  - A marine biological invasion is a natural process accelerated by human
      activities, and the crab Charybdis hellerii is an example of a globally
      widespread invasive species. This study evaluated color variation in C. hellerii
      and its relationship to the sex, size and sexual maturity of these crabs, and
      compared the efficiency of a freeware digital image-editing program with a
      commercially available program. The color of the individuals was analyzed using
      standardized digital images. The color pattern varied significantly with size;
      smaller and immature individuals were darker than larger and mature ones. The
      female abdomen changed in morphology and color with sexual maturity, becoming
      wider and orange-colored. There was no statistical difference in the color values
      between males and females and immature males did not show morphological or color
      differences in their abdomen. This study highlights the possible relationships of
      the color and physiological state of the reproductive system, which could help in
      future studies of behavior, avoiding the need to dissect and/or remove
      individuals from nature for assessment of sexual maturity. The freeware program
      showed the same efficiency in digital image analysis as a widely known commercial
      program.

PMID- 25761219
TI  - Functional properties of a Brazilian derived mouse embryonic stem cell line.
AB  - Pluripotent mouse embryonic stem cells (mESC) are cell lines derived from the
      inner cell mass of blastocyst-stage early mammalian embryos. Since ion channel
      modulation has been reported to interfere with both growth and differentiation
      process in mouse and human ESC it is important to characterize the
      electrophysiological properties of newly generated mESC and compare them to other
      lines. In this work, we studied the intercellular communication by way of gap
      junctions in a Brazilian derived mESC (USP-1, generated by Dr. Lygia Pereira's
      group) and characterized its electrophysiological properties. We used
      immunofluorescence and RT-PCR to reveal the presence of connexin 43 (Cx43),
      pluripotency markers and ion channels. Using a co-culture of neonatal mouse
      cardiomyocytes with mESC, where the heart cells expressed the enhanced Green
      Fluorescent Protein, we performed dye injections to assess functional coupling
      between the two cell types observing dye diffusion. The patch-clamp study showed
      outward currents identified as two types of potassium currents, transient outward
      potassium current (Ito) and delayed rectifier outward potassium current (Iks), by
      use of specific drug blockage. Calcium or sodium currents in undifferentiated
      mESC were not identified. We conclude that USP-1 mESC has functional Cx43
      channels establishing intercellular communication among themselves and with
      cardiomyocytes and has a similar electrophysiological profile compared to other
      mESC cell lines.

PMID- 25761220
TI  - The overexpression of SOX2 affects the migration of human teratocarcinoma cell
      line NT2/D1.
AB  - The altered expression of the SOX2 transcription factor is associated with
      oncogenic or tumor suppressor functions in human cancers. This factor regulates
      the migration and invasion of different cancer cells. In this study we
      investigated the effect of constitutive SOX2 overexpression on the migration and
      adhesion capacity of embryonal teratocarcinoma NT2/D1 cells derived from a
      metastasis of a human testicular germ cell tumor. We detected that increased SOX2
      expression changed the speed, mode and path of cell migration, but not the
      adhesion ability of NT2/D1 cells. Additionally, we demonstrated that SOX2
      overexpression increased the expression of the tumor suppressor protein p53 and
      the HDM2 oncogene. Our results contribute to the better understanding of the
      effect of SOX2 on the behavior of tumor cells originating from a human testicular
      germ cell tumor. Considering that NT2/D1 cells resemble cancer stem cells in many
      features, our results could contribute to the elucidation of the role of SOX2 in
      cancer stem cells behavior and the process of metastasis.

PMID- 25761222
TI  - Dissociation as a mediator of the relationship between childhood trauma and
      nonsuicidal self-injury in females: a path analytic approach.
AB  - New theoretical models of nonsuicidal self-injury (NSSI) postulate that symptoms
      subsequent to childhood maltreatment rather than childhood maltreatment itself
      may lead to engagement in NSSI. However, little is known concerning which
      specific syndromes serve as underlying mechanisms. In this study we sought to
      examine the mediating effects of dissociative, posttraumatic, and depressive
      symptoms, 3 often comorbid syndromes following childhood trauma. In addition, we
      aimed to assess differences between women with and without NSSI. A sample of 87
      female inpatients with a history of childhood abuse and neglect was divided into
      2 subgroups (NSSI: n = 42, no NSSI: n = 45). The assessment included measures of
      NSSI characteristics; adverse childhood experiences; and posttraumatic,
      dissociative, and depressive symptoms. The NSSI group reported significantly more
      cases of childhood maltreatment and higher levels of current dissociative,
      posttraumatic, and depressive symptoms than patients without NSSI. The results of
      a path analysis showed that only dissociation mediated the relationship between a
      history of child maltreatment and NSSI when all 3 psychopathological variables
      were included in the model. The findings point toward a strong and rather
      specific association between dissociative experiences and NSSI and therefore have
      important implications for clinical practice. 

PMID- 25761221
TI  - General aspects of muscle glucose uptake.
AB  - Glucose uptake in peripheral tissues is dependent on the translocation of GLUT4
      glucose transporters to the plasma membrane. Studies have shown the existence of
      two major signaling pathways that lead to the translocation of GLUT4. The first,
      and widely investigated, is the insulin activated signaling pathway through
      insulin receptor substrate-1 and phosphatidylinositol 3-kinase. The second is the
      insulin-independent signaling pathway, which is activated by contractions.
      Individuals with type 2 diabetes mellitus have reduced insulin-stimulated glucose
      uptake in skeletal muscle due to the phenomenon of insulin resistance. However,
      those individuals have normal glucose uptake during exercise. In this context,
      physical exercise is one of the most important interventions that stimulates
      glucose uptake by insulin-independent pathways, and the main molecules involved
      are adenosine monophosphate-activated protein kinase, nitric oxide, bradykinin,
      AKT, reactive oxygen species and calcium. In this review, our main aims were to
      highlight the different glucose uptake pathways and to report the effects of
      physical exercise, diet and drugs on their functioning. Lastly, with the better
      understanding of these pathways, it would be possible to assess, exactly and
      molecularly, the importance of physical exercise and diet on glucose homeostasis.
      Furthermore, it would be possible to assess the action of drugs that might
      optimize glucose uptake and consequently be an important step in controlling the
      blood glucose levels in diabetic patients, in addition to being important to
      clarify some pathways that justify the development of drugs capable of mimicking
      the contraction pathway. 

PMID- 25761223
TI  - Cancer genomics: the challenge of drug accessibility.
AB  - PURPOSE OF REVIEW: Although significant strides have been made in genome
      sequencing technology, target-drug matching remains challenging. This article
      highlights the difficulties associated with patients accessing targeted drugs
      based on genomic information, and some proposed solutions. RECENT FINDINGS:
      Although cancers are increasingly stratified according to molecular subgroups,
      challenges remain in improving patient outcome based on drug-target matching.
      Before a drug-target match is even proposed, significant expertise is required of
      the clinician to interpret genomic information. Once a potential match is made,
      barriers remain for patients to access treatment via clinical trials, as approved
      agents on-label or off-label, or through expanded access programs. Solutions to
      improve drug accessibility are actively being investigated. Several prospective
      trials using molecular characterization as an entry to access target-drug
      matching are underway. For those unable to access target-drug matching on trial,
      proposals for a facilitated access program and registry have been suggested.
      SUMMARY: Although improvements have been made in the drug development and
      approval timelines, drug accessibility based on molecular characterization
      remains problematic. However, with the emergence of novel trial designs, and
      efforts to enhance drug access outside of clinical trial settings, opportunities
      for drug-target matching are improving.

PMID- 25761225
TI  - Disrupting disruptive physicians.

PMID- 25761224
TI  - Cooperative lignification of xylem tracheary elements.
AB  - The development of xylem tracheary elements (TEs)--the hydro-mineral sap
      conducting cells--has been an evolutionary breakthrough to enable long distance
      nutrition and upright growth of vascular land plants. To allow sap conduction,
      TEs form hollow laterally reinforced cylinders by combining programmed cell death
      and secondary cell wall formation. To ensure their structural resistance for sap
      conduction, TE cell walls are reinforced with the phenolic polymer lignin, which
      is deposited after TE cell death by the cooperative supply of monomers and other
      substrates from the surrounding living cells.

PMID- 25761226
TI  - Direct observation of interfacial Au atoms on TiO2 in three dimensions.
AB  - Interfacial atoms, which result from interactions between the metal nanoparticles
      and support, have a large impact on the physical and chemical properties of
      nanoparticles. However, they are difficult to observe; the lack of knowledge has
      been a major obstacle toward unraveling their role in chemical transformations.
      Here we report conclusive evidence of interfacial Au atoms formed on the rutile
      (TiO2) (110) surfaces by activation using high-temperature (~500  degrees C)
      annealing in air. Three-dimensional imaging was performed using depth-sectioning
      enabled by aberration-corrected scanning transmission electron microscopy.
      Results show that the interface between Au nanocrystals and TiO2 (110) surfaces
      consists of a single atomic layer with Au atoms embedded inside Ti-O. The number
      of interfacial Au atoms is estimated from ~1-8 in an interfacial atomic column.
      Direct impact of interfacial Au atoms is observed on an enhanced Au-TiO2
      interaction and the reduction of surface TiO2; both are critical to Au catalysis.

PMID- 25761227
TI  - Modelling and simulation of complex sociotechnical systems: envisioning and
      analysing work environments.
AB  - Accurate comprehension and analysis of complex sociotechnical systems is a
      daunting task. Empirically examining, or simply envisioning the structure and
      behaviour of such systems challenges traditional analytic and experimental
      approaches as well as our everyday cognitive capabilities. Computer-based models
      and simulations afford potentially useful means of accomplishing sociotechnical
      system design and analysis objectives. From a design perspective, they can
      provide a basis for a common mental model among stakeholders, thereby
      facilitating accurate comprehension of factors impacting system performance and
      potential effects of system modifications. From a research perspective, models
      and simulations afford the means to study aspects of sociotechnical system design
      and operation, including the potential impact of modifications to structural and
      dynamic system properties, in ways not feasible with traditional experimental
      approaches. This paper describes issues involved in the design and use of such
      models and simulations and describes a proposed path forward to their development
      and implementation. PRACTITIONER SUMMARY: The size and complexity of real-world
      sociotechnical systems can present significant barriers to their design,
      comprehension and empirical analysis. This article describes the potential
      advantages of computer-based models and simulations for understanding factors
      that impact sociotechnical system design and operation, particularly with respect
      to process and occupational safety.

PMID- 25761228
TI  - Fast and living ring-opening polymerization of alpha-amino acid N
      carboxyanhydrides triggered by an "alliance" of primary and secondary amines at
      room temperature.
AB  - A novel highly efficient strategy, based on an "alliance" of primary and
      secondary amine initiators, was successfully developed allowing the fast and
      living ring-opening polymerization (ROP) of alpha-amino acid N-carboxyanhydrides
      (NCAs) at room temperature. 

PMID- 25761229
TI  - Infant and child deaths: Parent concerns about subsequent pregnancies.
AB  - PURPOSE: Examine parents' concerns about subsequent pregnancies after
      experiencing an infant or child death (newborn to 18 years). DATA SOURCES: Thirty
      nine semistructured parent (white, black, Hispanic) interviews 7 and 13 months
      post infant/child death conducted in English and/or Spanish, audio-recorded,
      transcribed, and content analyzed. Mothers' mean age was 31.8 years, fathers' was
      39 years; 11 parents were white, 16 black, and 12 Hispanic. CONCLUSIONS: Themes
      common at 7 and 13 months: wanting more children; fear, anxiety, scared; praying
      to God/God's will; thinking about/keeping the infant's/child's memory and at 7
      months importance of becoming pregnant for family members; and at 13 months happy
      about a new baby. Parents who lost a child in neonatal intensive care unit (NICU)
      commented more than those who lost a child in pediatric intensive care unit
      (PICU). Black and Hispanic parents commented more on praying to God and
      subsequent pregnancies being God's will than white parents. IMPLICATIONS FOR
      PRACTICE: Loss of an infant/child is a significant stressor on parents with
      documented negative physical and mental health outcomes. Assessing parents'
      subsequent pregnancy plans, recognizing the legitimacy of their fears about
      another pregnancy, discussing a plan should they encounter problems, and
      carefully monitoring the health of all parents who lost an infant/child is an
      essential practitioner role.

PMID- 25761230
TI  - Cyclic isoDGR and RGD peptidomimetics containing bifunctional diketopiperazine
      scaffolds are integrin antagonists.
AB  - The cyclo[DKP-isoDGR] peptidomimetics 2-5, containing bifunctional
      diketopiperazine (DKP) scaffolds that differ in the configuration of the two DKP
      stereocenters and in the substitution at the DKP nitrogen atoms, were prepared
      and examined in vitro in competitive binding assays with purified alphav beta3
      and alphav beta5 integrin receptors. IC50 values ranged from low nanomolar
      (ligand 3) to submicromolar with alphav beta3 integrin. The biological activities
      of ligands cyclo[DKP3-RGD] 1 and cyclo[DKP3-isoDGR] 3, bearing the same
      bifunctional DKP scaffold and showing similar alphaV beta3 integrin binding
      values, were compared in terms of their cellular effects in human U373
      glioblastoma cells. Compounds 1 and 3 displayed overlapping inhibitory effects on
      the FAK/Akt integrin activated transduction pathway and on integrin-mediated cell
      infiltration processes, and qualify therefore, despite the different RGD and
      isoDGR sequences, as integrin antagonists. Both compounds induced apoptosis in
      glioma cells after 72 hour treatment. 

PMID- 25761232
TI  - Anatomy of screw dislocations in nanoporous SAPO-18 as revealed by atomic force
      microscopy.
AB  - Defects in solids are often the source of functional activity, the trigger for
      crystal growth and the seat of instability. Screw dislocations are notoriously
      difficult to study by electron microscopy. Here we decipher the complex anatomy
      of one such defect in the industrially important nanoporous catalyst SAPO-18 by
      atomic force microscopy. 

PMID- 25761231
TI  - The effect of sterilization on silk fibroin biomaterial properties.
AB  - The effects of common sterilization techniques on the physical and biological
      properties of lyophilized silk fibroin sponges are described. Sterile silk
      fibroin sponges were cast using a pre-sterilized silk fibroin solution under
      aseptic conditions or post-sterilized via autoclaving, gamma radiation, dry heat,
      exposure to ethylene oxide, or hydrogen peroxide gas plasma. Low average
      molecular weight and low concentration silk fibroin solutions could be sterilized
      via autoclaving or filtration without significant loses of protein. However,
      autoclaving reduced the molecular weight distribution of the silk fibroin protein
      solution, and silk fibroin sponges cast from autoclaved silk fibroin were
      significantly stiffer compared to sponges cast from unsterilized or filtered silk
      fibroin. When silk fibroin sponges were sterilized post-casting, autoclaving
      increased scaffold stiffness, while decreasing scaffold degradation rate in
      vitro. In contrast, gamma irradiation accelerated scaffold degradation rate.
      Exposure to ethylene oxide significantly decreased cell proliferation rate on
      silk fibroin sponges, which was rescued by leaching ethylene oxide into PBS prior
      to cell seeding. 

PMID- 25761233
TI  - The science of being a study participant: FEM-PrEP participants' explanations for
      overreporting adherence to the study pills and for the whereabouts of unused
      pills.
AB  - BACKGROUND: FEM-PrEP was unable to determine whether once-daily, oral
      emtricitabine/tenofovir disoproxil fumarate reduces the risk of HIV acquisition
      among women because of low adherence. Self-reported adherence was high, and pill
      count data suggested good adherence. Yet, drug concentrations revealed limited
      pill use. We conducted a follow-up study with former participants in Bondo,
      Kenya, and Pretoria, South Africa, to understand factors that had influenced
      overreporting of adherence and to learn the whereabouts of unused pills. METHODS:
      Qualitative, semistructured interviews were conducted with 88 participants, and
      quantitative, audio computer-assisted self-interviews were conducted with 224
      participants. We used thematic analysis and descriptive statistics to analyze the
      qualitative and quantitative data, respectively. RESULTS: In audio computer
      assisted self-interviews, 31% (n = 70) said they had overreported adherence; the
      main reason was the belief that nonadherence would result in trial termination
      (69%, n = 48). A considerable percentage (35%, n = 78) acknowledged discarding
      unused pills. Few acknowledged giving their pills to someone else (4%, n = 10),
      and even fewer acknowledged giving them to someone with HIV (2%, n = 5). Many
      participants in the semistructured interviews said other participants had counted
      and removed pills from their bottles to appear adherent. CONCLUSIONS: Despite
      repeated messages that nonadherence would not upset staff, participants
      acknowledged several perceived negative consequences of reporting nonadherence,
      which made it difficult to report accurately. Uneasiness continued in the follow
      up study, as many said they had not overreported during the trial. Efforts to
      improve self-reported measures should include identifying alternative methods for
      creating supportive environments that allow participants to feel comfortable
      reporting actual adherence.

PMID- 25761235
TI  - Towards the development and characterization of an easy handling sheet-like
      biohybrid bone substitute.
AB  - We designed a sheet-like bone substitute capable of adapting to different
      geometries and becoming a standard tissue-engineered process for bone surgery.
      Preosteoblastic cells were seeded on to a monolayer of calcium phosphate granules
      and cultured in a flat parallelepipedic cell culture chamber for 1 month. From
      the various diameters of the granules examined, the 80-200 MUm group exhibited
      the most homogeneous performances regarding both biological (cell morphology,
      viability, differentiation, and simple metabolic activity) and mechanical
      (cohesion and stress-strain behavior) properties. This sheet was easy to handle
      after extraction from the culture chamber and showed versatile geometry and
      flexibility, making it easy to use for surgeons, especially for small defects of
      the maxillofacial area. 

PMID- 25761234
TI  - Implementation and operational research: Integrated pre-antiretroviral therapy
      screening and treatment for tuberculosis and cryptococcal antigenemia.
AB  - OBJECTIVE: To demonstrate the feasibility of integrated screening for
      cryptococcal antigenemia and tuberculosis (TB) before antiretroviral therapy
      (ART) initiation and to assess disease specific and all-cause mortality in the
      first 6 months of follow-up. METHODS: We enrolled a cohort of HIV-infected, ART
      naive adults with CD4 counts <=250 cells per microliter in rural Uganda who were
      followed for 6 months after ART initiation. All subjects underwent screening for
      TB; those with CD4 <=100 cells per microliter also had cryptococcal antigen
      (CrAg) screening. For those who screened positive, standard treatment for TB or
      preemptive treatment for cryptococcal infection was initiated, followed by ART 2
      weeks later. RESULTS: Of 540 participants enrolled, pre-ART screening detected
      10.6% (57/540) with prevalent TB and 6.8% (12/177 with CD4 count <=100 cells/MUL)
      with positive serum CrAg. After ART initiation, 13 (2.4%) patients were diagnosed
      with TB and 1 patient developed cryptococcal meningitis. Overall 7.2% of
      participants died (incidence rate 15.6 per 100 person-years at risk). Death rates
      were significantly higher among subjects with TB and cryptococcal antigenemia
      compared with subjects without these diagnoses. In multivariate analysis,
      significant risk factors for mortality were male sex, baseline anemia of
      hemoglobin <=10 mg/dL, wasting defined as body mass index <=15.5 kg/m, and
      opportunistic infections (TB, positive serum CrAg). CONCLUSIONS: Pre-ART
      screening for opportunistic infections detects many prevalent cases of TB and
      cryptococcal infection. However, severely immunosuppressed and symptomatic HIV
      patients continue to experience high mortality after ART initiation.

PMID- 25761236
TI  - Cerebral water and ion balance remains stable when humans are exposed to acute
      hypoxic exercise.
AB  - BACKGROUND: Intense physical activity increases the prevalence of acute mountain
      sickness (AMS) that can occur within 10 h after ascent to altitudes above 1500 m
      and is likely related to development of cerebral edema. This study evaluated
      whether disturbed cerebral water and ion homeostasis can be detected when intense
      exercise is carried out in hypoxia and monitored the influence of muscle
      metabolism for changes in arterial variables. METHODS: On two separate days, in
      random order, 30 min cycling exercise was performed in either hypoxia (10% O2) or
      normoxia at an intensity that was exhaustive in the hypoxic trial (~120 W; n=9).
      RESULTS: Exercise in hypoxia affected muscle metabolism, as evidenced by higher
      (p<0.05) leg lactate release at 7.5 min and a continuous decline in arterial pH
      (p<0.001) that was not observed in normoxia. Middle cerebral artery flow velocity
      increased (p<0.01) with exercise under both circumstances. No cerebral net
      exchange of Na(+) or K(+) was evident. Likewise, no significant net-exchange of
      water over the brain was demonstrated and the arterial and jugular venous
      hemoglobin concentrations were similar. CONCLUSION: Challenging exercise in
      hypoxia for 30 min affected muscle metabolism and increased an index of cerebral
      blood flow, but cerebral net water and ion homeostasis remained stable. Thus,
      although AMS develops within hours and may be related to exercise-induced
      disturbance of cerebral ion and water balance, such changes are not detectable
      when subjects are exposed to acute 30 min maximal exercise in hypoxia.

PMID- 25761237
TI  - Species-dependent splice recognition of a cryptic exon resulting from a recurrent
      intronic CEP290 mutation that causes congenital blindness.
AB  - A mutation in intron 26 of CEP290 (c.2991+1655A>G) is the most common genetic
      cause of Leber congenital amaurosis (LCA), a severe type of inherited retinal
      degeneration. This mutation creates a cryptic splice donor site, resulting in the
      insertion of an aberrant exon (exon X) into ~50% of all CEP290 transcripts. A
      humanized mouse model with this mutation did not recapitulate the aberrant CEP290
      splicing observed in LCA patients, suggesting differential recognition of cryptic
      splice sites between species. To further assess this phenomenon, we generated two
      CEP290 minigene constructs, with and without the intronic mutation, and
      transfected these in cell lines of various species. RT-PCR analysis revealed that
      exon X is well recognized by the splicing machinery in human and non-human
      primate cell lines. Intriguingly, this recognition decreases in cell lines
      derived from species such as dog and rodents, and it is completely absent in
      Drosophila. In addition, other cryptic splicing events corresponding to sequences
      in intron 26 of CEP290 were observed to varying degrees in the different cell
      lines. Together, these results highlight the complexity of splice site
      recognition among different species, and show that care is warranted when
      generating animal models to mimic splice site mutations in vivo. 

PMID- 25761238
TI  - Trans-membrane area asymmetry controls the shape of cellular organelles.
AB  - Membrane organelles often have complicated shapes and differ in their volume,
      surface area and membrane curvature. The ratio between the surface area of the
      cytosolic and luminal leaflets (trans-membrane area asymmetry (TAA)) determines
      the membrane curvature within different sites of the organelle. Thus, the shape
      of the organelle could be critically dependent on TAA. Here, using mathematical
      modeling and stereological measurements of TAA during fast transformation of
      organelle shapes, we present evidence that suggests that when organelle volume
      and surface area are constant, TAA can regulate transformation of the shape of
      the Golgi apparatus, endosomal multivesicular bodies, and microvilli of brush
      borders of kidney epithelial cells. Extraction of membrane curvature by small
      spheres, such as COPI-dependent vesicles within the Golgi (extraction of positive
      curvature), or by intraluminal vesicles within endosomes (extraction of negative
      curvature) controls the shape of these organelles. For instance, Golgi tubulation
      is critically dependent on the fusion of COPI vesicles with Golgi cisternae, and
      vice versa, for the extraction of membrane curvature into 50-60 nm vesicles, to
      induce transformation of Golgi tubules into cisternae. Also, formation of
      intraluminal ultra-small vesicles after fusion of endosomes allows equilibration
      of their TAA, volume and surface area. Finally, when microvilli of the brush
      border are broken into vesicles and microvilli fragments, TAA of these membranes
      remains the same as TAA of the microvilli. Thus, TAA has a significant role in
      transformation of organelle shape when other factors remain constant. 

PMID- 25761239
TI  - Comparison of mutation profiles in the Duchenne muscular dystrophy gene among
      populations: implications for potential molecular therapies.
AB  - Novel therapeutic approaches are emerging to restore dystrophin function in
      Duchenne Muscular Dystrophy (DMD), a severe neuromuscular disease characterized
      by progressive muscle wasting and weakness. Some of the molecular therapies, such
      as exon skipping, stop codon read-through and internal ribosome entry site
      mediated translation rely on the type and location of mutations. Hence, their
      potential applicability worldwide depends on mutation frequencies within
      populations. In view of this, we compared the mutation profiles of the
      populations represented in the DMD Leiden Open-source Variation Database with
      original data from Mexican patients (n = 162) with clinical diagnosis of the
      disease. Our data confirm that applicability of exon 51 is high in most
      populations, but also show that differences in theoretical applicability of exon
      skipping may exist among populations; Mexico has the highest frequency of
      potential candidates for the skipping of exons 44 and 46, which is different from
      other populations (p < 0.001). To our knowledge, this is the first comprehensive
      comparison of theoretical applicability of exon skipping targets among specific
      populations. 

PMID- 25761240
TI  - A perilipin gene from Clonostachys rosea f. Catenulata HL-1-1 is related to
      sclerotial parasitism.
AB  - Clonostachys rosea f. catenulata is a promising biocontrol agent against many
      fungal plant pathogens. To identify mycoparasitism-related genes from C. rosea f.
      catenulata, a suppression subtractive hybridization (SSH) cDNA library of C.
      rosea f. catenulata HL-1-1 that parasitizes the sclerotia of S. sclerotiorum was
      constructed. 502 clones were sequenced randomly, and thereby 472 expressed
      sequence tags (ESTs) were identified. Forty-three unigenes were annotated and
      exhibited similarity to a wide diversity of genes. Quantitative real-time PCR
      showed that a perilipin-like protein encoding gene, Per3, was up-regulated by 6.6
      fold over the control at 96 h under the induction of sclerotia. The full-length
      sequence of Per3 was obtained via 5' and 3' rapid identification of cDNA ends.
      Overexpression of Per3 in HL-1-1 significantly enhanced the parasitic ability on
      sclerotia. The results indicated that Per3 might be involved in the
      mycoparasitism of C. rosea f. catenulata HL-1-1. This is the first report of a
      perilipin as a potential biocontrol gene in mycoparasites. The study provides
      usefu l insights into the interaction between C. rosea f. catenulata and fungal
      plant pathogens.

PMID- 25761241
TI  - Tetraspanin 8-rictor-integrin alpha3 complex is required for glioma cell
      migration.
AB  - The malignant glioma remains one of the most aggressive human malignancies with
      extremely poor prognosis. Glioma cell invasion and migration are the main causes
      of death. In the current study, we studied the expression and the potential
      functions of tetraspanin 8 (Tspan8) in malignant gliomas. We found that Tspan8
      expression level is high in both malignant glioma tissues and in several human
      glioma cell lines, where it formed a complex integrin alpha3 and rictor, the
      latter is a key component of mammalian target of rapamycin (mTOR) complex 2
      (mTORC2). Disruption of this complex, through siRNA-mediated knockdown of anyone
      of these three proteins, inhibited U251MG glioma cell migration in vitro. We
      further showed that Tspan8-rictor association appeared required for mTORC2
      activation. Knockdown of Tspan8 by the targeted siRNAs prevented mTOR-rictor
      (mTORC2) assembly as well as phosphorylation of AKT (Ser-473) and protein kinase
      C alpha (PKCalpha) in U251MG cells. Together, these results demonstrate that over
      expressed Tspan8 in malignant glioma forms a complex with rictor and integrin
      alpha3 to mediate mTORC2 activation and glioma cell migration. Therefore,
      targeting Tspan8-rictor-integrin alpha3 complex may provide a potential
      therapeutic intervention for malignant glioma. 

PMID- 25761242
TI  - Monitoring of apoptosis in 3D cell cultures by FRET and light sheet fluorescence
      microscopy.
AB  - Non-radiative cell membrane associated Forster Resonance Energy Transfer (FRET)
      from an enhanced cyan fluorescent protein (ECFP) to an enhanced yellow
      fluorescent protein (EYFP) is used for detection of apoptosis in 3-dimensional
      cell cultures. FRET is visualized in multi-cellular tumor spheroids by light
      sheet based fluorescence microscopy in combination with microspectral analysis
      and fluorescence lifetime imaging (FLIM). Upon application of staurosporine and
      to some extent after treatment with phorbol-12-myristate-13-acetate (PMA), a
      specific activator of protein kinase c, the caspase-3 sensitive peptide linker
      DEVD is cleaved. This results in a reduction of acceptor (EYFP) fluorescence as
      well as a prolongation of the fluorescence lifetime of the donor (ECFP).
      Fluorescence spectra and lifetimes may, therefore, be used for monitoring of
      apoptosis in a realistic 3-dimensional system, while light sheet based microscopy
      appears appropriate for 3D imaging at low light exposure. 

PMID- 25761243
TI  - Different apoptotic pathways activated by oxaliplatin in primary astrocytes vs.
      colo-rectal cancer cells.
AB  - Oxaliplatin-based chemotherapy improves the outcomes of metastatic colorectal
      cancer patients. Its most significant and dose-limiting side effect is the
      development of a neuropathic syndrome. The mechanism of the neurotoxicity is
      unclear. The limited knowledge about differences existing between neurotoxic and
      antitumor effects hinders the discovery of effective and safe adjuvant therapies.
      In vitro, we suggested cell-specific activation apoptotic pathways in normal
      nervous cells (astrocytes) vs. colon-cancer cells (HT-29). In the present
      research we compared the apoptotic signals evoked by oxaliplatin in astrocytes
      and HT-29 analyzing the intrinsic and extrinsic apoptotic pathways. In
      astrocytes, oxaliplatin induced a mitochondrial derangement measured as cytosolic
      release of cytochrome C, increase in superoxide anion levels and decreased
      expression of the antiapoptotic protein Bcl-2. Caspase-8, a main initiator of the
      extrinsic process remained unaltered. On the contrary, in HT-29 oxaliplatin
      increased caspase-8 activity and Bid expression, thus activating the extrinsic
      apoptosis, while the Bcl-2 increased expression blocked the mitochondrial damage.
      Data suggest the preferred activation of the intrinsic apoptosis as oxaliplatin
      damage signaling in normal nervous cells. The extrinsic pathway prevails in tumor
      cells indicating a possible strategy for planning new molecules to treat
      oxaliplatin-dependent neurotoxicity without negatively influence chemotherapy. 

PMID- 25761244
TI  - A heme oxygenase-1 transducer model of degenerative and developmental brain
      disorders.
AB  - Heme oxygenase-1 (HO-1) is a 32 kDa protein which catalyzes the breakdown of heme
      to free iron, carbon monoxide and biliverdin. The Hmox1 promoter contains
      numerous consensus sequences that render the gene exquisitely sensitive to
      induction by diverse pro-oxidant and inflammatory stimuli. In "stressed"
      astroglia, HO-1 hyperactivity promotes mitochondrial iron sequestration and
      macroautophagy and may thereby contribute to the pathological iron deposition and
      bioenergetic failure documented in Alzheimer disease, Parkinson disease and
      certain neurodevelopmental conditions. Glial HO-1 expression may also impact
      neuroplasticity and cell survival by modulating brain sterol metabolism and the
      proteasomal degradation of neurotoxic proteins. The glial HO-1 response may
      represent a pivotal transducer of noxious environmental and endogenous stressors
      into patterns of neural damage and repair characteristic of many human
      degenerative and developmental CNS disorders. 

PMID- 25761245
TI  - Adult neural stem cells: Long-term self-renewal, replenishment by the immune
      system, or both?
AB  - The current model of adult neurogenesis in mammals suggests that adult-born
      neurons are generated by stem cells that undergo long-term self-renewal, and that
      a lifetime supply of stem cells resides in the brain. In contrast, it has
      recently been demonstrated that adult-born neurons in crayfish are generated by
      precursors originating in the immune system. This is particularly interesting
      because studies done many years ago suggest that a similar mechanism might exist
      in rodents and humans, with bone marrow providing stem cells that can generate
      neurons. However, the relevance of these findings for natural mechanisms
      underlying adult neurogenesis in mammals is not clear, because of uncertainties
      at many levels. We argue here that the recent findings in crayfish send a strong
      signal to re-examine existing data from rodents and humans, and to design new
      experiments that will directly test the contributions of the immune system to
      adult neurogenesis in mammals. 

PMID- 25761246
TI  - Generation of bis-acyl ketals from esters and benzyl amines under oxidative
      conditions.
AB  - Treatment of benzylamines with esters at an elevated temperature are expected to
      give amides. However, in the presence of TBAI/TBHP, esters possessing a methylene
      carbon alpha-to oxygen with benzylamines provide bis-esters rather than the
      expected amides. Benzylamines under oxidative conditions generate less
      nucleophilic carboxylates, which couples at the sp(3) C-H bonds of esters and
      cyclic ethers to give bis-acyl ketals and alpha-acyloxy ethers, respectively. 

PMID- 25761248
TI  - The effect of sex-biased dispersal on opposite-sexed spatial genetic structure
      and inbreeding risk.
AB  - Natal sex-biased dispersal has long been thought to reduce the risk of inbreeding
      by spatially separating opposite-sexed kin. Yet, comprehensive and quantitative
      evaluations of this hypothesis are lacking. In this study, we quantified the
      effectiveness of sex-biased dispersal as an inbreeding avoidance strategy by
      combining spatially explicit simulations and empirical data. We quantified the
      extent of kin clustering by measuring the degree of spatial autocorrelation among
      opposite-sexed individuals (FM structure). This allowed us to systematically
      explore how the extent of sex-biased dispersal, generational overlap, and mate
      searching distance, influenced both kin clustering, and the resulting inbreeding
      in the absence of complementary inbreeding avoidance strategies. Simulations
      revealed that when sex-biased dispersal was limited, positive FM genetic
      structure developed quickly and increased as the mate searching distance
      decreased or as generational overlap increased. Interestingly, complete long
      range sex-biased dispersal did not prevent the development of FM genetic
      structure when generations overlapped. We found a very strong correlation between
      FM genetic structure and both FIS under random mating, and pedigree-based
      measures of inbreeding. Thus, we show that the detection of FM genetic structure
      can be a strong indicator of inbreeding risk. Empirical data for two species with
      different life history strategies yielded patterns congruent with our
      simulations. Our study illustrates a new application of spatial genetic
      autocorrelation analysis that offers a framework for quantifying the risk of
      inbreeding that is easily extendable to other species. Furthermore, our findings
      provide other researchers with a context for interpreting observed patterns of
      opposite-sexed spatial genetic structure. 

PMID- 25761249
TI  - The influence of surface passivation on electronic energy relaxation dynamics of
      CdSe and CdSe/CdS nanocrystals studied using visible and near infrared transient
      absorption spectroscopy.
AB  - Charge carrier relaxation dynamics of electronically excited CdSe and CdSe/CdS
      core/shell nanocrystals (NCs) were studied using femtosecond time-resolved
      transient absorption spectroscopy, employing both visible and near-infrared (NIR)
      probe laser pulses. Following 400 nm excitation, the combination of visible and
      NIR laser probe pulses were used to determine the influence of surface
      passivation on electronic relaxation dynamics for nanocrystals overcoated with
      either organic ligands or inorganic semiconductors. In particular, low-energy NIR
      photons were used to isolate transient absorption signals due to either electron
      and hole intraband transitions. Four relaxation components were detected for CdSe
      NCs passivated by organic molecules: (1) picosecond hole relaxation; (2) electron
      deep trapping; (3) electron surface trapping; and (4) exciton radiative
      recombination. Based on TA data collected over a broad energy range, electron
      deep trapping at Se(2-) sites was suppressed for CdSe NCs passivated by inorganic
      (CdS) semiconducting materials. By comparing the time-dependent transient
      absorption data of a series of CdSe/CdS NCs with different shell thicknesses,
      evidence for the transition from Type-I to quasi Type-II NCs was obtained. These
      data illustrate the sensitivity of femtosecond time-resolved transient absorption
      measurements carried out over visible and near infrared probe energies for
      determining the influence of nanocrystal structure on electronic relaxation
      dynamics. 

PMID- 25761250
TI  - Straightforward synthesis of 5-bromopenta-2,4-diynenitrile and its reactivity
      towards terminal alkynes: a direct access to diene and benzofulvene scaffolds.
AB  - The high-yielding synthesis of 5-bromopenta-2,4-diynenitrile (BrC5 N) was
      achieved for the first time. Its reactivity with triisopropylsilylacetylene and
      triisopropylsilylbutadiyne in the presence of copper and palladium as co
      catalysts and diisopropylamine was evaluated. It revealed an unprecedented
      cascade reaction leading to a diene in one case and to a benzofulvene in the
      other case, with a unique structure. Both of them were characterized by X-ray
      crystallography, among other techniques. The mechanism of the reaction leading to
      the diene was investigated experimentally. Theoretical calculations at the DFT
      level suggest that the mechanism leading to the benzofulvene relies on a hexa
      dehydro Diels-Alder (HDDA)-type of mechanism. This work constitutes an example of
      an unanticipated reactivity leading to an important increase of chemical
      complexity. 

PMID- 25761251
TI  - Crystal structure of A-site deficient La0.2Sr0.7-xCaxTiO3 perovskite at ambient
      conditions and high temperatures: a neutron powder diffraction study.
AB  - The crystal structures of several members of the solid solution perovskite
      La(0.2)Sr(0.7-x)CaxTiO(3) were investigated using the Rietveld analysis of
      neutron powder diffraction patterns collected in ambient conditions and high
      temperatures. At room temperature, samples showed a tetragonal I4/mcm symmetry
      for compositions with 0.1 <=x<= 0.35 followed by a phase transition to the
      orthorhombic Pbnm symmetry for compositions with 0.4 <=x<= 0.7. Samples with the
      orthorhombic symmetry showed two reversible phase transitions in the temperature
      range 20  degrees C-900  degrees C. The first phase transition was a
      discontinuous Pbnm-I4/mcm around 300  degrees C and the second was a continuous
      I4/mcm-Pm3[combining macron]m transition around 900  degrees C. The lower
      symmetries resulted from very small distortions and changes in tilts of the BO(6)
      octahedra of this perovskite material; which was a direct result from the A-site
      ionic radius mismatch.

PMID- 25761253
TI  - First approximation to congenital malformation rates in embryos and hatchlings of
      sea turtles.
AB  - BACKGROUND: Congenital malformations in sea turtles have been considered
      sporadical. Research carried out in the Mexican Pacific revealed high levels of
      congenital malformations in the olive ridley, but little or no information is
      available for other species. We present results from analyses of external
      congenital malformations in olive ridley, green, and hawskbill sea turtles from
      Mexican rookeries on the Pacific coast and Gulf of Mexico. METHODS: We examined
      150 green and hawksbill nests and 209 olive ridley nests during the 2010 and 2012
      nesting seasons, respectively. Olive ridley eggs were transferred to a hatchery
      and incubated in styrofoam boxes. Nests from the other two species were left in
      situ. Number of eggs, live and dead hatchlings, and eggs with or without
      embryonic development were registered. Malformation frequency was evaluated with
      indices of prevalence and severity. RESULTS: Mortality levels, prevalence and
      severity were higher in olive ridley than in hawksbill and green sea turtles.
      Sixty-three types of congenital malformations were observed in embryos, and dead
      or live hatchlings. Of these, 38 are new reports; 35 for wild sea turtles, three
      for vertebrates. Thirty-one types were found in hawksbill, 23 in green, and 59 in
      olive ridley. The head region showed a higher number of malformation types.
      Malformation levels in the olive ridley were higher than previously reported.
      CONCLUSION: Olive ridleys seem more prone to the occurrence of congenital
      malformations than the other two species. Whether the observed malformation
      levels are normal or represent a health problem cannot be currently ascertained
      without long-term assessments.

PMID- 25761252
TI  - P2X7R is involved in the progression of atherosclerosis by promoting NLRP3
      inflammasome activation.
AB  - Purinergic 2X7 receptor (P2X7R) and nucleotide-binding oligomerization domain
      like receptor protein 3 (NLRP3) are expressed in macrophages in atherosclerotic
      lesions. However, the mechanisms through which P2X7R participates in the
      inflammatory response in atherosclerosis remain largely unknown. The aim of the
      present study was to investigate the role of P2X7R in atherosclerosis and the
      mechanisms of action of the NLRP3 inflammasome following stimulation with
      oxidized low-density lipoprotein (oxLDL). We observed the expression and
      distribution of P2X7R in the atherosclerotic plaque in the coronary arteries from
      an autopsy specimen and in that of the aortic sinuses of apoE(-/-) mice by
      immunohistochemistry and immunofluorescence staining. The specificity of short
      interfering RNA (siRNA) was used to suppress P2X7R and NLRP3 mRNA expression. RT
      qPCR and western blot analysis were used to analyze mRNA and protein expression,
      respectively. Co-immunoprecipitation was used to examine the interaction between
      protein kinase R (PKR) phosphorylation and NLRP3. P2X7R and NLRP3 were expressed
      at high levels in the atherosclerotic plaque in the coronary arteries.
      Stimulation with oxLDL upregulated P2X7R, NLRP3 and interleukin (IL)-1beta
      expression. P2X7R knockdown by siRNA suppressed NLRP3 inflammasome activation by
      inhibiting the PKR phosphorylation mediated by oxLDL. In the atherosclerotic
      lesions in the aortic sinuses of apoE(-/-) mice, P2X7R expression was found at
      high levels. Moreover, P2X7R siRNA attenuated the development of atherosclerosis
      in the apoE(-/-) mice. In conclusion, our results demonstrate that P2X7R plays a
      significant role in the development of atherosclerosis and regulates NLRP3
      inflammasome activation by promoting PKR phosphorylation.

PMID- 25761254
TI  - Development of antisense oligonucleotide (ASO) technology against Tgf-beta
      signaling to prevent scarring during flexor tendon repair.
AB  - Flexor tendons (FT) in the hand provide near frictionless gliding to facilitate
      hand function. Upon injury and surgical repair, satisfactory healing is hampered
      by fibrous adhesions between the tendon and synovial sheath. In the present study
      we used antisense oligonucleotides (ASOs), specifically targeted to components of
      Tgf-beta signaling, including Tgf-beta1, Smad3 and Ctgf, to test the hypothesis
      that local delivery of ASOs and suppression of Tgf-beta1 signaling would enhance
      murine FT healing by suppressing adhesion formation while maintaining strength.
      ASOs were injected in to the FT repair site at 2, 6 and 12 days post-surgery. ASO
      treatment suppressed target gene expression through 21 days. Treatment with Tgf
      beta1, Smad3 or Ctgf ASOs resulted in significant improvement in tendon gliding
      function at 14 and 21 days, relative to control. Consistent with a decrease in
      adhesions, Col3a1 expression was significantly decreased in Tgf-beta1, Smad3 and
      Ctgf ASO treated tendons relative to control. Smad3 ASO treatment enhanced the
      maximum load at failure of healing tendons at 14 days, relative to control. Taken
      together, these data support the use of ASO treatment to improve FT repair, and
      suggest that modulation of the Tgf-beta1 signaling pathway can reduce adhesions
      while maintaining the strength of the repair.

PMID- 25761255
TI  - Brief report: Response inhibition and processing speed in children with motor
      difficulties and developmental coordination disorder.
AB  - A previous study reported that children with poor motor skills, classified as
      having motor difficulties (MD) or Developmental Coordination Disorder (DCD),
      produced more errors in a motor response inhibition task compared to typically
      developing (TD) children but did not differ in verbal inhibition errors. The
      present study investigated whether these groups differed in the length of time
      they took to respond in order to achieve these levels of accuracy, and whether
      any differences in response speed could be explained by generally slow
      information processing in children with poor motor skills. Timing data from the
      Verbal Inhibition Motor Inhibition test were analyzed to identify differences in
      performance between the groups on verbal and motor inhibition, as well as on
      processing speed measures from standardized batteries. Although children with MD
      and DCD produced more errors in the motor inhibition task than TD children, the
      current analyses found that they did not take longer to complete the task.
      Children with DCD were slower at inhibiting verbal responses than TD children,
      while the MD group seemed to perform at an intermediate level between the other
      groups in terms of verbal inhibition speed. Slow processing speed did not account
      for these group differences. Results extended previous research into response
      inhibition in children with poor motor skills by explicitly comparing motor and
      verbal responses, and suggesting that slow performance, even when accurate, may
      be attributable to an inefficient way of inhibiting responses, rather than slow
      information processing speed per se. 

PMID- 25761257
TI  - Stability of carotid artery under steady-state and pulsatile blood flow: a fluid
      structure interaction study.
AB  - It has been shown that arteries may buckle into tortuous shapes under lumen
      pressure, which in turn could alter blood flow. However, the mechanisms of artery
      instability under pulsatile flow have not been fully understood. The objective of
      this study was to simulate the buckling and post-buckling behaviors of the
      carotid artery under pulsatile flow using a fully coupled fluid-structure
      interaction (FSI) method. The artery wall was modeled as a nonlinear material
      with a two-fiber strain-energy function. FSI simulations were performed under
      steady-state flow and pulsatile flow conditions with a prescribed flow velocity
      profile at the inlet and different pressures at the outlet to determine the
      critical buckling pressure. Simulations were performed for normal (160 ml/min)
      and high (350 ml/min) flow rates and normal (1.5) and reduced (1.3) axial stretch
      ratios to determine the effects of flow rate and axial tension on stability. The
      results showed that an artery buckled when the lumen pressure exceeded a critical
      value. The critical mean buckling pressure at pulsatile flow was 17-23% smaller
      than at steady-state flow. For both steady-state and pulsatile flow, the high
      flow rate had very little effect (<5%) on the critical buckling pressure. The
      fluid and wall stresses were drastically altered at the location with maximum
      deflection. The maximum lumen shear stress occurred at the inner side of the bend
      and maximum tensile wall stresses occurred at the outer side. These findings
      improve our understanding of artery instability in vivo. 

PMID- 25761258
TI  - A study of optical absorption of cysteine-capped CdSe nanoclusters using first
      principles calculations.
AB  - Understanding the size-dependent structures and properties of ligand-capped
      nanoclusters in solvent is of particular interest for the design, synthesis and
      application of II-VI colloidal QDs. Using DFT and TDDFT calculations, we studied
      the structure and optical property evolution of the cysteine-capped (CdSe)N
      clusters of N = 1-10, 13, 16 and 19 in gas, toluene, water and alkaline aqueous
      solution, and made a comparison with their corresponding bare clusters. The
      cysteine binds with (CdSe)Nvia several patterns depending on the medium they
      exist in, affecting the cluster structures and in consequence their optical
      absorption. In general, the absorption bands of (CdSe)N blueshift when cysteine
      is added, and the shift varies with the interaction strength between the cluster
      and the ligand, and the dielectric constant of the solvent. However, bare
      clusters retain their size sensitivity, in particular the redshift trend with
      increasing cluster size, and some similarity was noted for the optical absorption
      of the bare and ligated clusters regardless of the gas or solvent media.
      Population analysis reveals that the excitations are mainly from orbitals
      distributing on the (CdSe)N part, while the ligand is negligibly involved in the
      excitations. This is an important feature for the II-VI QDs as biosensors with
      which the information of biomolecules is detected from the size dependent optical
      absorption or emission of the QDs other than the biomolecules. 

PMID- 25761259
TI  - Vinylation of aldehydes using Mn/Cr alloy and a N4 -ligand/Ni(II) -catalyst.
AB  - We report an efficient and practical protocol for the Cr/Ni-catalyzed vinylation
      of aldehydes, based on the use of Mn/Cr alloy (ca. 10 % Cr) and TMSCl. No
      additional Cr salts need to be added. In the presence of NiCl2 (0.3 mol %) and a
      bis(ketimino)-2,2'-bipyridine as N4 -chelating ligand (1 mol %), the vinylations
      proceed smoothly at room temperature. The presence of catalytic amounts of MeOH
      and LiOAc as additives was found to further promote the efficiency of the
      catalytic system, even in the absence of the ligand. Detailed reaction monitoring
      revealed that LiOAc accelerates the product alcohol silylation, thus increasing
      the turnover rate.

PMID- 25761260
TI  - CortiQ-based Real-Time Functional Mapping for Epilepsy Surgery.
AB  - PURPOSE: To evaluate the use of the cortiQ-based mapping system (g.tec medication
      engineering GmbH, Austria) for real-time functional mapping (RTFM) and to compare
      it to results from electrical cortical stimulation mapping (ESM) and functional
      magnetic resonance imaging (fMRI). METHODS: Electrocorticographic activity was
      recorded in 3 male patients with intractable epilepsy by using cortiQ mapping
      system and analyzed in real time. Activation related to motor, sensory, and
      receptive language tasks was determined by evaluating the power of the high gamma
      frequency band (60-170 Hz). The sensitivity and specificity of RTFM were tested
      against ESM and fMRI results. RESULTS: "Next-neighbor" approach demonstrated
      [sensitivity/specificity %] (1) RTFM against ESM: 100.00/79.70 for hand motor;
      100.00/73.87 for hand sensory; -/87 for language (it was not identified by the
      ESM); (2) RTFM against fMRI: 100.00/84.4 for hand motor; 66.70/85.35 for hand
      sensory; and 87.85/77.70 for language. CONCLUSIONS: The results of the
      quantitative "next-neighbor" RTFM evaluation were concordant to those from ESM
      and fMRI. The RTFM correlates well with localization of hand motor function
      provided by ESM and fMRI, which may offer added localization in the operating
      room and guidance for extraoperative ESM mapping. Real-time functional mapping
      correlates with fMRI language activation when ESM findings are negative. It has
      fewer limitations than ESM and greater flexibility in activation paradigms and
      measuring responses.

PMID- 25761261
TI  - A novel sensory nerve conduction study technique to evaluate the sural nerve from
      the forefoot to the knee.
AB  - PURPOSE: Length-dependent polyneuropathy is common. Current electrophysiological
      methods cannot assess sensory nerve function proximal to the distal calf,
      limiting their utility in the quantification of severity of length-dependent
      polyneuropathy. METHODS: The authors developed a novel electrophysiological
      approach for distal to proximal assessment of the sural nerve between the
      forefoot and the knee and tested it on 63 healthy young, middle-aged, and old
      adults. RESULTS: It was feasible to elicit sensory nerve action potentials in the
      forefoot, ankle, and knee segments of the sural nerve in all subjects.
      Intraobserver (r = 0.87) and interobserver (r = 0.87) reliability were high.
      Sensory nerve action potential amplitudes were greatest at the ankle, followed by
      the knee and forefoot. Sensory nerve action potential amplitudes in the forefoot
      and ankle were significantly smaller in the old age group (>60 years) compared
      with the young age group (20-39 years) (P < 0.05). In contrast, neither age nor
      gender had a significant impact on sensory nerve action potential conduction
      velocities. CONCLUSIONS: The authors demonstrated that reliable
      electrophysiological recordings of the sural nerve as proximal as the knee are
      feasible. This novel technique may be useful in patients with length-dependent
      polyneuropathy to monitor progression and to evaluate treatment response.

PMID- 25761262
TI  - Cyanobacterial Oxygenic Photosynthesis is Protected by Flavodiiron Proteins.
AB  - Flavodiiron proteins (FDPs, also called flavoproteins, Flvs) are modular enzymes
      widely present in Bacteria and Archaea. The evolution of cyanobacteria and
      oxygenic photosynthesis occurred in concert with the modulation of typical
      bacterial FDPs. Present cyanobacterial FDPs are composed of three domains, the
      beta-lactamase-like, flavodoxin-like and flavin-reductase like domains.
      Cyanobacterial FDPs function as hetero- and homodimers and are involved in the
      regulation of photosynthetic electron transport. Whilst Flv2 and Flv4 proteins
      are limited to specific cyanobacterial species (beta-cyanobacteria) and function
      in photoprotection of Photosystem II, Flv1 and Flv3 proteins, functioning in the
      "Mehler-like" reaction and safeguarding Photosystem I under fluctuating light
      conditions, occur in nearly all cyanobacteria and additionally in green algae,
      mosses and lycophytes. Filamentous cyanobacteria have additional FDPs in
      heterocyst cells, ensuring a microaerobic environment for the function of the
      nitrogenase enzyme under the light. Here, the evolution, occurrence and
      functional mechanisms of various FDPs in oxygenic photosynthetic organisms are
      discussed. 

PMID- 25761263
TI  - CaCO3 precipitation in multilayered cyanobacterial mats: clues to explain the
      alternation of micrite and sparite layers in calcareous stromatolites.
AB  - Marine cyanobacterial mats were cultured on coastal sediments (Niva Bay, Oresund,
      Denmark) for over three years in a closed system. Carbonate particles formed in
      two different modes in the mat: (i) through precipitation of submicrometer-sized
      grains of Mg calcite within the mucilage near the base of living cyanobacterial
      layers, and (ii) through precipitation of a variety of mixed Mg calcite/aragonite
      morphs in layers of degraded cyanobacteria dominated by purple sulfur bacteria.
      The d13C values were about 20/00 heavier in carbonates from the living
      cyanobacterial zones as compared to those generated in the purple bacterial
      zones. Saturation indices calculated with respect to calcite, aragonite, and
      dolomite inside the mats showed extremely high values across the mat profile.
      Such high values were caused by high pH and high carbonate alkalinity generated
      within the mats in conjunction with increased concentrations of calcium and
      magnesium that were presumably stored in sheaths and extracellular polymer
      substances (EPS) of the living cyanobacteria and liberated during their post
      mortem degradation. The generated CaCO3 morphs were highly similar to morphs
      reported from heterotrophic bacterial cultures, and from bacterially decomposed
      cyanobacterial biomass emplaced in Ca-rich media. They are also similar to CaCO3
      morphs precipitated from purely inorganic solutions. No metabolically
      (enzymatically) controlled formation of particular CaCO3 morphs by heterotrophic
      bacteria was observed in the studied mats. The apparent alternation of in vivo
      and post-mortem generated calcareous layers in the studied cyanobacterial mats
      may explain the alternation of fine-grained (micritic) and coarse-grained
      (sparitic) laminae observed in modern and fossil calcareous cyanobacterial
      microbialites as the result of a probably similar multilayered mat organization. 

PMID- 25761265
TI  - The art of being joyful.

PMID- 25761256
TI  - Brazilian consensus on photoprotection.
AB  - Brazil is a country of continental dimensions with a large heterogeneity of
      climates and massive mixing of the population. Almost the entire national
      territory is located between the Equator and the Tropic of Capricorn, and the
      Earth axial tilt to the south certainly makes Brazil one of the countries of the
      world with greater extent of land in proximity to the sun. The Brazilian
      coastline, where most of its population lives, is more than 8,500 km long. Due to
      geographic characteristics and cultural trends, Brazilians are among the peoples
      with the highest annual exposure to the sun. Epidemiological data show a
      continuing increase in the incidence of non-melanoma and melanoma skin cancers.
      Photoprotection can be understood as a set of measures aimed at reducing sun
      exposure and at preventing the development of acute and chronic actinic damage.
      Due to the peculiarities of Brazilian territory and culture, it would not be
      advisable to replicate the concepts of photoprotection from other developed
      countries, places with completely different climates and populations. Thus the
      Brazilian Society of Dermatology has developed the Brazilian Consensus on
      Photoprotection, the first official document on photoprotection developed in
      Brazil for Brazilians, with recommendations on matters involving photoprotection.

PMID- 25761266
TI  - Big data and the future of nursing knowledge.

PMID- 25761264
TI  - Haloferax volcanii, as a Novel Tool for Producing Mammalian Olfactory Receptors
      Embedded in Archaeal Lipid Bilayer.
AB  - The aim of this study was to explore the possibility of using an archaeal
      microorganism as a host system for expressing mammalian olfactory receptors
      (ORs). We have selected the archaeon Haloferax volcanii as a cell host system and
      one of the most extensively investigated OR, namely I7-OR, whose preferred
      ligands are short-chain aldehydes, such as octanal, heptanal, nonanal. A novel
      plasmid has been constructed to express the rat I7-OR, fused with a hexahistidine
      tag for protein immunodetection. The presence of the recombinant receptor at a
      membrane level was demonstrated by immunoblot of the membranes isolated from the
      transgenic archaeal strain. In addition, the lipid composition of
      archaeonanosomes containing ORs has been characterized in detail by High
      Performance Thin-Layer Chromatography (HPTLC) in combination with Matrix-Assisted
      Laser Desorption Ionization-Time-Of-Flight/Mass Spectrometry (MALDI-TOF/MS)
      analysis. 

PMID- 25761272
TI  - A photoinduced cyclization cascade-total synthesis of (-)-leuconoxine.
AB  - A protecting-group-free and enantioselective total synthesis of the monoterpenoid
      indole alkaloid (-)-leuconoxine was accomplished. The key step comprises a novel
      photoinduced domino macrocyclization/transannular cyclization involving the
      Witkop cyclization, for which additional mechanistic evidence is provided. This
      process furnishes a diaza[5.5.6.6]fenestrane skeleton, which is a hitherto
      unprecedented structure element. 

PMID- 25761274
TI  - Excited state dynamics and isomerization in ruthenium sulfoxide complexes.
AB  - Molecular photochromic compounds are those that interconvert between two isomeric
      forms with light. The two isomeric forms display distinct electronic and
      molecular structures and must not be in equilibrium with one another. These light
      activated molecular switch compounds have found wide application in areas of
      study ranging from chemical biology to materials science, where conversion from
      one isomeric form to another by light prompts a response in the environment
      (e.g., protein or polymeric material). Certain ruthenium and osmium polypyridine
      sulfoxide complexes are photochromic. The mode of action is a phototriggered
      isomerization of the sulfoxide from S- to O-bonded. The change in ligation
      drastically alters both the spectroscopic and electrochemical properties of the
      metal complex. Our laboratory has pioneered the preparation and study of these
      complexes. In particular, we have applied femtosecond pump-probe spectroscopy to
      reveal excited state details of the isomerization mechanism. The data from
      numerous complexes allowed us to predict that the isomerization was nonadiabatic
      in nature, defined as occurring from a S-bonded triplet excited state (primarily
      metal-to-ligand charge transfer in character) to an O-bonded singlet ground state
      potential energy surface. This prediction was corroborated by high-level density
      functional theory calculations. An intriguing aspect of this reactivity is the
      coupling of nuclear motion to the electronic wave function and how this coupling
      affects motions productive for isomerization. In an effort to learn more about
      this coupling, we designed a project to examine phototriggered isomerization in
      bis-sulfoxide complexes. The goal of these studies was to determine whether
      certain complexes could be designed in which a single photon excitation event
      would prompt two sulfoxide isomerizations. We employed chelating sulfoxides in
      this study and found that both the nature of the chelate ring and the R group on
      the sulfoxide affect the photochemical reactivity. For example, this reactivity
      may be tuned such that two sulfoxide ligands isomerize sequentially following two
      successive excitations or that two sulfoxide ligands isomerize following a single
      excitation. This Account explains our understanding to date of this
      photochemistry. 

PMID- 25761273
TI  - Ion specific effects: decoupling ion-ion and ion-water interactions.
AB  - Ion-specific effects in aqueous solution, known as the Hofmeister effect, are
      prevalent in diverse systems ranging from pure ionic to complex protein
      solutions. The objective of this paper is to explicitly demonstrate how complex
      ion-ion and ion-water interactions manifest themselves in the Hofmeister effect
      based on a series of recent experimental observations. These effects are not
      considered in the classical descriptions of ion effects, such as the Derjaguin
      Landau-Verwey-Overbeek (DLVO) theory, and therefore they fail to describe the
      origin of the phenomenological Hofmeister effect. However, given that models
      considering the basic forces of electrostatic and van der Waals interactions can
      offer rationalization for the core experimental observations, a universal
      interaction model stands a chance of being developed. In this perspective, we
      separately derive the contribution from ion-ion electrostatic interactions and
      ion-water interactions from second harmonic generation (SHG) data at the air-ion
      solution interface, which yields an estimate of the ion-water interactions in
      solution. The Hofmeister ion effect observed for biological solutes in solution
      should be similarly influenced by contributions from ion-ion and ion-water
      interactions, where the same ion-water interaction parameters derived from SHG
      data at the air-ion solution interface could be applicable. A key experimental
      data set available from solution systems to probe ion-water interactions is the
      modulation of water diffusion dynamics near ions in a bulk ion solution, as well
      as near biological liposome surfaces. This is obtained from Overhauser dynamic
      nuclear polarization (ODNP), a nuclear magnetic resonance (NMR) relaxometry
      technique. The surface water diffusivity is influenced by the contribution from
      ion-water interactions, both from localized surface charges and adsorbed ions,
      although the relative contribution of the former is larger on liposome surfaces.
      In this perspective, ion-water interaction energy values derived from
      experimental data for various ions are compared with theoretical values in the
      literature. Ultimately, quantifying ion-induced changes in the surface energy for
      the purpose of developing valid theoretical models for ion-water interactions
      will be critical to rationalizing the Hofmeister effect. 

PMID- 25761278
TI  - What causes the facing-the-viewer bias in biological motion?
AB  - Orthographically projected biological motion point-light displays are generally
      ambiguous with respect to their orientation in depth, yet observers consistently
      prefer the facing-the-viewer interpretation. There has been discussion as to
      whether this bias can be attributed to the social relevance of biological motion
      stimuli or relates to local, low-level stimulus properties. In the present study
      we address this question. In Experiment 1, we compared the facing-the-viewer bias
      produced by a series of four stick figures and three human silhouettes that
      differed in posture, gender, and the presence versus absence of walking motion.
      Using a paradigm in which we asked observers to indicate the spinning direction
      of these figures, we found no bias when participants observed silhouettes,
      whereas a pronounced degree of bias was elicited by most stick figures. We
      hypothesized that the ambiguous surface normals on the lines and dots that
      comprise stick figures are prone to a visual bias that assumes surfaces to be
      convex. The local surface orientations of the occluding contours of silhouettes
      are unambiguous, and as such the convexity bias does not apply. In Experiment 2,
      we tested the role of local features in ambiguous surface perception by adding
      dots to the elbows and knees of silhouettes. We found biases consistent with the
      facing directions implied by a convex body surface. The results unify a number of
      findings regarding the facing-the-viewer bias. We conclude that the facing-the
      viewer bias is established at the level of surface reconstruction from local
      image features rather than on a semantic level. 

PMID- 25761279
TI  - Volume perception: Disparity extraction and depth representation in complex three
      dimensional environments.
AB  - Our sensitivity to binocular disparity is exquisite under the best conditions,
      typically in uncluttered scenes with few small objects. Yet binocular vision can
      deliver a very strong impression of depth for complex, cluttered scenes with lots
      of objects and overlaps. How good is disparity processing under these conditions?
      Here we explored a novel task: depth volume perception, to study how a global
      representation of depth is obtained using binocular disparity information. We
      found that the human visual system is sensitive to depth volume but that the
      volume perceived is dependent on the local and global arrangement of scene
      content. We also show how a model of early disparity extraction and combination
      can account for some of the biases found. Our work shows that the visual system
      is not able to correctly represent and interpret disparity for all locations in a
      complex three-dimensional scene. 

PMID- 25761280
TI  - Future path and tangent point models in the visual control of locomotion in curve
      driving.
AB  - Studying human behavior in the natural context of everyday visual tasks-
      including locomotor tasks such as driving--can reveal visual strategies or even
      suggest underlying visual mechanisms. This paper reviews empirical and
      theoretical work in the past 20 years (1994-2014) on the visual control of
      steering a vehicle along a winding path-one of the most comprehensively studied
      forms of visually guided locomotion in humans. The focus is on on-road studies of
      visual behavior and what they can reveal about the visual strategies in curve
      driving. Theoretical models and results from simulator studies are discussed
      where they have direct relevance to the interpretation of on-road data. For the
      past 20 years, the point of departure in studies of curve driving has been
      tangent point orientation, and tangent point models (models based on tracking the
      tangent point) have become established as the default account of how vision is
      used in curve negotiation. More recent studies have questioned the generality of
      the tangent point hypothesis, however, arguing that in addition to (or instead
      of) the tangent point, drivers target visual reference points on their future
      path. Ecological validity of real-world studies often comes at the cost of
      methodological challenges that make the data difficult to interpret in terms of
      underlying mechanisms, and the limitations of existing data and the complementary
      roles of real-world and laboratory studies are discussed.

PMID- 25761281
TI  - Using functional magnetic resonance imaging to explore the flashed face
      distortion effect.
AB  - The flashed face distortion (FFD) effect was coined by Tangen, Murphy, and
      Thompson (2011) in their second-place winner of the 2012 Best Illusion of the
      Year Contest. The FFD arises when people view various eye-aligned faces that are
      sequentially flashed in the visual periphery, and gradually the faces appear to
      be deformed and grotesque. In this functional magnetic resonance imaging (fMRI)
      study, participants were presented with four conditions: (a) one face pair
      changing only its illumination; (b) two and (c) three alternating face pairs; and
      (d) nonrepeated face pairs. Participants rated the magnitude of each illusion
      immediately after each block. Results showed that the receptive region of the
      early visual cortex (V1-V4), and category-selective areas such as the fusiform
      face area (FFA) and occipital face area (OFA), responded proportionally to the
      participants' rated FFD strength. A random-effects voxelwise analysis further
      revealed positively correlated areas (including the medial and superolateral
      frontal areas) and negatively correlated areas (including the precuneus,
      postcentral gyrus, right insula, and bilateral middle frontal gyri) with respect
      to participants' ratings. Time series correlations among these nine ROIs (four
      positive and five negative) indicated that most participants showed a clustering
      of the two separate ROI types. Exploratory factor analysis (EFA) also
      demonstrated the segregation of the positive and negative ROIs; additionally, two
      subsystems were identified within the negative ROIs. These results suggest that
      the FFD is mediated by at least two networks: one that is likely responsible for
      perception and another that is likely responsible for subjective feelings and
      engagement. 

PMID- 25761282
TI  - Binocular contributions to linear vertical vection.
AB  - Compelling illusions of self-motion, known as vection, can be produced in a
      stationary observer by visual stimulation alone. The role of binocular vision and
      stereopsis in these illusions was explored in a series of three experiments.
      Previous research had provided evidence of stereoscopic enhancements for linear
      vection in depth (e.g., Palmisano, 1996, 2002). Here we examined for the first
      time the effects of binocular vision and stereopsis on linear vertical vection.
      Vertical vection was induced by the upward or downward translation of large
      stereoscopic surfaces. These surfaces were horizontally oriented depth
      corrugations produced by disparity modulation of patterns of persistent or short
      lifetime dot elements. We found that binocular viewing of such surfaces
      significantly increased the magnitudes and decreased the onset delays of vertical
      vection. Experiments utilizing short lifetime dot stereograms demonstrated that
      these particular binocular enhancements of vection were due to the motion of
      stereoscopically defined features. 

PMID- 25761283
TI  - Adaptive model of the aging emmetropic eye and its changes with accommodation.
AB  - A general schematic model of the optical system of the emmetropic human eye is
      proposed, capable of adapting to changes with age and accommodation through
      adjustment of the optical surfaces and the internal gradient index structure of
      the lens. The specific models of the cornea and lens consist of minor
      generalizations of previous work by assuming them to be the sum of a biconic plus
      three higher order Zernike modes. The internal gradient index distribution adapts
      to the external shape so that the analytical expression is invariant with the
      changes with age and accommodation. The model also includes tips, tilts, and
      decentrations of the surfaces according to experimental findings. The specific
      parameters of these models are either constants or functions of age and/or
      accommodation. The model is polychromatic, and its optical performance was
      evaluated along the keratometric axis. Chromatic aberrations (longitudinal and
      transverse), astigmatism, coma, trefoil, and spherical aberration show good
      agreement with experimental averages. The change of these aberrations as a
      function of age or accommodation is also consistent with experimental findings
      (except for trefoil in eyes older than 50 years). This means that the average
      structure seems to predict the average performance. Nevertheless, the present
      model is too schematic to account for other higher order aberrations, such as
      tetrafoil, also present in real eyes. 

PMID- 25761284
TI  - The pupillary light response reflects exogenous attention and inhibition of
      return.
AB  - Here we show that the pupillary light response reflects exogenous (involuntary)
      shifts of attention and inhibition of return. Participants fixated in the center
      of a display that was divided into a bright and a dark half. An exogenous cue
      attracted attention to the bright or dark side of the display. Initially, the
      pupil constricted when the bright, as compared to the dark, side of the display
      was cued, reflecting a shift of attention toward the exogenous cue. Crucially,
      this pattern reversed about 1 s after cue presentation. This later-occurring,
      relative dilation (when the bright side was cued) reflected disengagement from
      the previously attended location, analogous to the behavioral phenomenon of
      inhibition of return. Indeed, we observed a reliable correlation between
      "pupillary inhibition" and behavioral inhibition of return. Our results support
      the view that inhibition of return results from habituation to (or short-term
      depression of) visual input. We conclude that the pupillary light response is a
      complex eye movement that reflects how we selectively parse and interpret visual
      input. 

PMID- 25761285
TI  - Long-term stable, low-temperature remote silicate phosphor thick films printed on
      a glass substrate.
AB  - A critical step in providing better phosphor solution for white light emitting
      diode (LED) is to utilize inexpensive silicate phosphors with strong thermal
      stability. Here, we demonstrate yellow silicate phosphor-embedded glass thick
      films with a high luminous efficacy of ~32 lm/W at 200 mA as a nonconventional
      remote-phosphor approach. The simple screen-printing process of a paste
      consisting of (Ba,Sr,Ca)2SiO4:Eu2+ phosphor and a low softening point glass
      creates a planar remote structure on a regular soda lime silicate glass with
      controllable film thickness and location (top vs bottom) of the phosphor layer.
      The glass matrix provides promising densification and adhesion with the substrate
      at the optimal low temperature of 410  degrees C, with the long-term stability in
      luminous efficacy over 500 h of operation. The proposed phosphor structure has
      important implications to overcome current limitations as phosphors.

PMID- 25761288
TI  - [Fighting mosquitoes in the Netherlands: risks and control of exotic mosquitoes].
AB  - Mosquitoes play a significant role globally in the transmission of so-called
      vector-borne diseases. In the Netherlands, native mosquitoes are capable of
      transmitting infectious disease. This has not resulted in outbreaks of disease
      over the last 50 years. The establishment of exotic mosquito species could pose
      risks to public health, especially in the case of the Asian tiger mosquito (Aedes
      albopictus). Several organisations are working together to prevent the
      establishment of exotic mosquitoes in the Netherlands. A plan for controlling
      native mosquito species is also currently being developed.

PMID- 25761289
TI  - [Increased risk of type II diabetes mellitus and cardiovascular disease after
      gestational diabetes mellitus: a systematic review].
AB  - OBJECTIVE: To determine the long-term risk of developing type II diabetes (T2D)
      and cardiovascular disease (CVD) for women with a history of gestational diabetes
      mellitus. DESIGN: Systematic review and meta-analysis. METHOD: Two search
      strategies were used in PubMed and Embase to determine the long-term risks of
      developing T2D and CVD after a pregnancy complicated by gestational diabetes
      mellitus. After critical appraisal of the papers found, 11 papers were included,
      involving a total of 328,423 patients. Absolute and relative risks (RRs) were
      calculated. RESULTS: Eight studies (n=276,829) reported on the long-term risk of
      T2D and 4 (n=141,048) on the long-term risk of CVD. Follow-up ranged from 3.5 to
      11.5 years for T2D and from 1.2 to 74.0 years for CVD. Women with gestational
      diabetes had a risk of T2D varying between 9.5% and 37.0% and a risk of CVD of
      between 0.28% and 15.5%. Women with gestational diabetes were at increased risk
      of T2D (weighted RR: 13.2; 95% CI: 8.5-20.7) and CVD (weighted RR: 2.0; 95% CI:
      1.1-3.7) compared to women without gestational diabetes. CONCLUSION: Women with
      prior gestational diabetes mellitus have a significantly increased risk of
      developing T2D and CVD. It is very important that gestational diabetes is
      recognised as a cardiovascular risk factor in daily practice. It would be
      desirable to screen this group of women for the presence of hyperglycaemia and
      other cardiovascular risk factors. Further research is required to be able to
      specify the long-term risk of T2D and CVD and to demonstrate whether such
      screening is cost-effective.

PMID- 25761290
TI  - [Breast-conserving surgery and radiotherapy as a one-day procedure].
AB  - A single dose of irradiation to the lumpectomy cavity alone after breast
      conserving surgery in breast cancer patients has been available in the
      Netherlands since 2011. This new treatment modality is used in the Haaglanden
      Medical Centre in The Hague and in the Catharina Hospital in Eindhoven. The goal
      of intraoperative radiation therapy is to limit the patient burden caused by
      whole breast irradiation, while maintaining excellent local tumour control. The
      technique is used only in patients with a low probability of recurrent disease in
      the breast. Approximately 150 patients receive intraoperative radiation therapy
      each year In the Netherlands, an estimated 4,000 breast cancer patients were
      eligible in 2013 for this new treatment technique or another method of partial
      breast irradiation. In both hospitals the results are closely monitored. Only 15
      of the first 200 patients experienced a side effect within a period of 3 months
      after intraoperative radiation therapy. These side effects were successfully
      treated either with antibiotics or with surgery. 

PMID- 25761291
TI  - [Crohn's disease: a controversy].
AB  - In 1932, the New York City-based gastroenterologist, Burril B. Crohn, published
      the manuscript 'Regional Ileitis' in The Journal of the American Medical
      Association (JAMA). This publication is responsible for the current designation
      of Crohn's disease. Despite the fact that this ground-breaking article lead to
      the improved description and recognition of this gastrointestinal disease, the
      choice for the name Crohn's disease was not always straightforward. This article
      discusses the controversy between Crohn and his colleagues Ginzburg and
      Oppenheimer, about the naming of the disease. In addition, it touches on the
      recognition of phenotypes that vary from Crohn's original depiction. 

PMID- 25761292
TI  - [A neonate with a sacrococcygeal mass].
AB  - A neonate was born with a sacrococcygeal mass. Initially, spina bifida was
      suspected. However, neurological examination was unremarkable. An MRI of the
      neuraxis showed a large cystic presacral lesion without signs of spina bifida.
      Surgical resection of the lesion was performed. Pathologic evaluation confirmed
      the diagnosis of a sacrococcygeal teratoma. 

PMID- 25761293
TI  - [Progressive cognitive disturbances in a 17-year-old boy].
AB  - BACKGROUND: Subacute sclerosing panencephalitis (SSPE) is a fatal encephalitis
      manifesting a number of years after a primary measles infection. This disease has
      become very rare since the introduction of immunisation against measles in 1976.
      CASE DESCRIPTION: A 17-year-old boy presented with progressive cognitive
      disturbances and extrapyramidal symptoms that had developed over a few weeks. He
      had not been immunised because of his parents' religious beliefs, and had
      contracted measles at 4 years of age. An EEG was performed on the basis of
      clinical suspicion of SSPE, and showed the SSPE-specific, characteristic pattern
      of periodic complexes as described by Radermecker. The diagnosis of SSPE was
      confirmed by cerebrospinal fluid examination. Our patient died 4 months after
      initial diagnosis. CONCLUSION: SSPE is still occurring in the Netherlands. The
      absence of effective treatment underlines the importance of prevention by means
      of immunization against measles.

PMID- 25761294
TI  - [Predictive value of the VMS theme 'Frail elderly': delirium, falling and
      mortality in elderly hospital patients].
AB  - OBJECTIVE: To determine the predictive value of safety management system (VMS)
      screening questions for falling, delirium, and mortality, as punt down in the VMS
      theme 'Frail elderly'. DESIGN: Retrospective observational study. METHOD: We
      selected all patients >= 70 years who were admitted to non-ICU wards at the
      Deventer Hospital, the Netherlands, for at least 24 hours between 28 March 2011
      and 10 June 2011. On admission, patients were screened with the VMS instrument by
      a researcher. Delirium and falls were recorded during hospitalisation. Six months
      after hospitalisation, data on mortality were collected. RESULTS: We included 688
      patients with a median age of 78.7 (range: 70.0-97.1); 50.7% was male. The
      sensitivity of the screening for delirium risk was 82%, the specificity 62%. The
      sensitivity of the screening for risk of falling was 63%, the specificity 65%.
      Independent predictors for mortality within 6 months were delirium risk (odds
      ratio (OR): 2.3; 95% CI 1.1-3.2), malnutrition (OR: 2.1; 95% CI 1.3-3.5),
      admission to a non-surgical ward (OR: 3.0; 95% CI 1.8-5.1), and older age (OR:
      1.1; 95%CI 1.0-1.1). Patients classified by the VMS theme 'Frail elderly' as
      having more risk factors had a higher risk of dying (p < 0.001). CONCLUSIONS: The
      VMS screening for delirium is a reasonably reliable instrument for identifying
      those elderly people with a high risk of developing this condition; the VMS
      sensitivity for fall risk is moderate. The number of positive VMS risk factors
      correlates with mortality and may therefore be regarded as a measure of frailty.

PMID- 25761295
TI  - [Regulatory burden of clinical research].
AB  - A few recent reports in both daily newspapers and interviews indicate that
      investigators working on trials in the Netherlands are experiencing too much red
      tape, that regulations are getting too strict, and that they are being asked to
      do things which, in their view, are not really important. This impairs their
      efforts in delivering good research. Analysis shows that no new legislation has
      been introduced since the implementation of the EU Clinical Trial Directive in
      2004. Over this 8-year period, the number of clinical research projects submitted
      nationwide has remained almost steady at approximately 1,800 per year. Of these a
      steady 42% are investigator-initiated studies. Recent new guidance from the FDA
      and MHRA indicates that over-interpretation of rules has indeed occurred. The
      newly promoted risk-based methodologies allow things to change. A potentially
      'leaner' way forward has also been discussed. 

PMID- 25761296
TI  - [A man with haematochezia and abdominal pain].
AB  - A 83-year-old male was admitted to the Emergency Department with acute
      haematochezia and abdominal pain. At digital rectal examination multiple soft
      distensions were palpable. Sigmoidoscopy revealed ischaemia of the rectum with
      severe gangrene. The patient was discharged after fluid resuscitation. Follow-up
      sigmoidoscopy 4 weeks later showed a fully recovered rectum. 

PMID- 25761297
TI  - [NHG guideline 'Deep-vein thrombosis and pulmonary embolus'].
AB  - The revised Dutch College of General Practitioners (Nederlands Huisartsen
      Genootschap [NHG]) guideline 'Deep-vein thrombosis and pulmonary embolus'
      includes recommendations for the treatment of patients with deep-vein thrombosis
      (DVT) and thrombophlebitis, and for the exclusion of pulmonary embolism (PE). The
      general practitioner (GP) can exclude the presence of DVT or PE in some patients
      by using a decision rule and a D-dimer test. When using D-dimer test as a point
      of-care test, meticulous care is essential during the test procedure and storage
      of blood. The GP can treat many patients with DVT; the NHG guideline does not
      advise use of direct oral anticoagulants. In the case of an isolated DVT in the
      calf, treatment with anticoagulants or ultrasound follow-up can be chosen in
      consultation with the patient or on the basis of regional agreements. In the case
      of patients with superficial thrombophlebitis, a wait-and-see approach is usually
      sufficient.

PMID- 25761299
TI  - [New potassium binders effective: treatment of hyperkalaemia secondary to RAAS
      inhibitors].
AB  - This commentary discusses two recent publications by Weir et al. and Packham et
      al. in The New England Journal of Medicine on the efficacy of two novel potassium
      binders, sodium zirconium cyclosilicate and patiromer. In a similar manner to
      existing potassium binders, these drugs exchange dietary potassium for either
      sodium or calcium in the gut, thereby preventing absorption of potassium. Both
      drugs were tested against placebo in patients with chronic kidney disease who
      developed hyperkalaemia because they were also using renin-angiotensin
      aldosterone system (RAAS) inhibitors. Both drugs lowered serum potassium
      effectively and were tolerated reasonably well. A strong point in the trials is
      that the new potassium binders allow patients to continue using RAAS inhibitors.
      By doing so, these patients with high cardiovascular risk may continue to benefit
      from the protective effects of RAAS inhibitors. Limitations include the
      relatively short treatment period, the lack of a control group using existing
      potassium binders, and the exclusion of patients with severe or symptomatic
      hyperkalaemia. 

PMID- 25761304
TI  - Aftereffect of motion-in-depth based on binocular cues: Effects of adaptation
      duration, interocular correlation, and temporal correlation.
AB  - There are at least two possible binocular cues to motion-in-depth, namely
      disparity change over time and interocular velocity differences. There has been
      significant controversy about their relative contributions to the perception of
      motion-in-depth. In the present study, we used the technique of selective
      adaptation to address this question. In Experiment 1, we found that adaptation to
      motion-in-depth depicted by temporally correlated random-dot stereograms, which
      contained coherent interocular velocity difference, produced motion aftereffect
      in the depth direction irrespective of the adaptors' interocular correlation for
      any adaptation duration tested. This suggests that coherent changing disparity
      does not contribute to motion-in-depth adaptation. Because the aftereffect
      duration did not saturate in the tested range of adaptation duration, it is
      unlikely that the lack of the effect of changing disparity was due to a ceiling
      effect. In Experiment 2, we used a novel adaptor that contained a unidirectional
      coherent interocular velocity difference signal and a bidirectional changing
      disparity signal that should not induce a motion aftereffect in depth. Following
      the adaptation, motion aftereffect in depth occurred in the opposite direction to
      the adaptor's motion-in-depth based on interocular velocity difference.
      Experiment 3 demonstrated that these results generalized in 12 untrained
      subjects. These experiments suggest that the contribution of interocular velocity
      difference to the perception of motion-in-depth is substantial, while that of
      changing disparity is very limited (if any), at least at the stages of direction
      selective mechanisms subject to an aftereffect phenomenon. 

PMID- 25761303
TI  - Doped SnO2 transparent conductive multilayer thin films explored by continuous
      composition spread.
AB  - Mn-doped SnO2 thin films were fabricated by a continuous composition spread (CCS)
      method on a glass substrate at room temperature to find optimized compositions.
      The fabricated materials were found to have a lower resistivity than pure SnO2
      thin films because of oxygen vacancies generated by Mn doping. As Mn content was
      increased, resistivity was found to decrease for limited doping concentrations.
      The minimum thin film resistivity was 0.29 Omega-cm for a composition of 2.59 wt
      % Mn-doped SnO2. The Sn-O vibrational stretching frequency in FT-IR showed a blue
      shift, consistent with oxygen deficiency. Mn-doped SnO2/Ag/Mn-doped SnO2
      multilayer structures were fabricated using this optimized composition deposited
      by an on-axis radio frequency (RF) sputter. The multilayer transparent conducting
      oxide film had a resistivity of 7.35 * 10-5 Omega-cm and an average transmittance
      above 86% in the 550 nm wavelength region.

PMID- 25761305
TI  - On the relation between nontarget object location and avoidance responses.
AB  - The presence of nontarget objects influences kinematic parameters of reaches
      toward target objects. In previous studies, several different nontarget positions
      have been used. Taken together, these studies suggest that when the horizontal or
      vertical distance to nontargets is decreased, avoidance responses are more
      pronounced. Furthermore, responses to nontarget objects are asymmetrical across
      workspace, i.e., responses in the presence of equidistant nontargets on the
      inside and the outside of the reaching arm are different. However, these studies
      have provided a coarse overall picture of the effect of nontarget location.
      Therefore, the aim of this experiment was to systematically map the avoidance
      responses across the workspace in order to determine in detail the relation
      between nontarget position and the avoidance response. Specifically, we were
      interested in the contribution of four parameters to the reaching response: the
      nontarget's horizontal and vertical position, its distance from the starting
      position, and its angle with the vertical midline of the workspace. Participants
      were asked to perform reaches towards physical targets while nontargets were
      present in 1 of 24 different positions. Our results replicate horizontal and
      vertical effects of the nontarget object on reaching behavior. We also replicate
      stronger avoidances of nontargets on the outside of the reaching limb compared to
      nontargets on the inside. Furthermore, our results provide a detailed overview of
      the interaction between these factors and demonstrate that there is a "hot"
      region qua nontarget positions that prompt the strongest responses. Lastly, our
      results provide evidence that support a fine-grained spatial resolution of
      nontarget motor representation. 

PMID- 25761306
TI  - Synthesis of strongly fluorescent graphene quantum dots by cage-opening
      buckminsterfullerene.
AB  - Graphene quantum dots is a class of graphene nanomaterials with exceptional
      luminescence properties. Precise dimension control of graphene quantum dots
      produced by chemical synthesis methods is currently difficult to achieve and
      usually provides a range of sizes from 3 to 25 nm. In this work, fullerene C60 is
      used as starting material, due to its well-defined dimension, to produce very
      small graphene quantum dots (~2-3 nm). Treatment of fullerene C60 with a mixture
      of strong acid and chemical oxidant induced the oxidation, cage-opening, and
      fragmentation processes of fullerene C60. The synthesized quantum dots were
      characterized and supported by LDI-TOF MS, TEM, XRD, XPS, AFM, STM, FTIR, DLS,
      Raman spectroscopy, and luminescence analyses. The quantum dots remained fully
      dispersed in aqueous suspension and exhibited strong luminescence properties,
      with the highest intensity at 460 nm under a 340 nm excitation wavelength.
      Further chemical treatments with hydrazine hydrate and hydroxylamine resulted in
      red- and blue-shift of the luminescence, respectively. 

PMID- 25761307
TI  - Transfusion safety from the viewpoint of a musical quintet.

PMID- 25761308
TI  - Blocking phenomenon occurs with murine monoclonal antibodies (anti-Fy(a)) in a
      neonate with a positive direct antiglobulin test due to maternal anti-Fy(a).

PMID- 25761309
TI  - A good manufacturing practice method to ex vivo expand natural killer cells for
      clinical use.
AB  - BACKGROUND: Great interest has been raised recently by the design of new adoptive
      immunotherapeutic strategies based on the in vivo infusion of ex vivo-expanded
      and activated natural killer (NK) cells. The development of good manufacturing
      practice (GMP) methods for the efficient production of fully functional NK cells
      is mandatory for clinical application. MATERIALS AND METHODS: Peripheral blood
      mononuclear cells were obtained by leukapheresis and processed in the GMP
      facility. For NK-cell enrichment, a two-step immunomagnetic procedure consisting
      of CD3(+) T-cell depletion followed by CD56(+) cell positive selection was used.
      Isolated NK cells were suspended in serum-free medium containing autologous
      plasma, interleukin (IL)-2 and IL-15 in the presence of irradiated autologous
      feeder cells and cultured for 14 days at 37  degrees C. IL-2 and IL-15 were also
      added during the last 24 hours of culture. Expanded cells underwent full quality
      control testing for cytogenetic characteristics, viability, sterility, phenotype
      and endotoxin status; functional tests, such as degranulation assays and
      cytotoxicity, were performed on expanded NK cells before cryopreservation and
      after thawing. RESULTS: NK-cell populations expanded on average 15.7+/-4.7 fold
      by day 14, with a viability of 96% +/-0.5. At the end of the incubation period,
      97% +/-1.1 of the expanded population was CD56(+) NK cells; these effector cells
      showed significant up-regulation of the activating receptors NKG2D and DNAM-1.
      Functional tests demonstrated that expanded NK cells are fully functional with no
      difference whether tested before cryopreservation or after thawing. DISCUSSION:
      These data provide the basis for developing new NK-cell-based immunotherapeutic
      strategies for the treatment of patients with cancer.

PMID- 25761310
TI  - Factors associated with psychological and physiological stress reactions to blood
      donation: a systematic review of the literature.

PMID- 25761311
TI  - Transfusion of ABO non-identical platelets does not influence the clinical
      outcome of patients undergoing autologous haematopoietic stem cell
      transplantation.
AB  - BACKGROUND: There are ABO antigens on the surface of platelets, but whether ABO
      compatible platelets are necessary for transfusions is a matter of ongoing
      debate. We retrospectively reviewed the ABO matching of platelet transfusions in
      a subset of patients undergoing autologous haematopoietic progenitor cell
      transplantation during a 14-year period. Our aim was to analyse the
      characteristics and outcomes of patients who received platelet transfusions that
      were or were not ABO identical. MATERIAL AND METHODS: We analysed 529 consecutive
      patients with various haematological and non-haematological diseases who
      underwent 553 autologous progenitor stem cell transplants at the University
      Hospital la Fe between January 2000 and December 2013. We retrospectively
      analysed and compared transfusion and clinical outcomes of patients according to
      the ABO match of the platelet transfusions received. The period analysed was the
      time from transplantation until discharge. RESULTS: The patients received a total
      of 2,772 platelet concentrates, of which 2,053 (74.0%) were ABO identical and 719
      (26.0%) ABO non-identical; of these latter 309 were compatible and 410
      incompatible with the patients' plasma. Considering all transplants, 36 (6.5%)
      did not require any platelet transfusions, while in 246 (44.5%) cases, the
      patients were exclusively transfused with ABO identical platelets and in 47
      (8.5%) cases they received only ABO non-identical platelet transfusions. The
      group of patients who received both ABO identical and ABO non-identical platelet
      transfusions had higher transfusion needs and worse clinical outcomes compared to
      patients who received only ABO identical or ABO non-identical platelets.
      DISCUSSION: In our hospital, patients undergoing autologous haematopoietic stem
      cell transplantation who received ABO identical or ABO non-identical platelet
      transfusions had similar transfusion and clinical outcomes. The isolated fact of
      receiving ABO non-identical platelets did not influence morbidity or survival.

PMID- 25761312
TI  - Genomic analysis of para-Bombay individuals in south-eastern China: the
      possibility of linkage and disequilibrium between FUT1 and FUT2.
AB  - BACKGROUND: The para-Bombay phenotype results from a variety of mutations in the
      alpha-(1,2)-fucosyltransferase gene (FUT1). We investigated samples from seven
      Chinese probands serologically typed as having the para-Bombay phenotype.
      MATERIALS AND METHODS: The para-Bombay phenotype was identified by standard
      serological methods. Genetic mutations of FUT1 and FUT2 genes were analysed by
      DNA sequencing. Heterozygous mutations of FUT1 were identified by TOPO cloning
      sequencing. Blood samples from 331 randomly-selected Chinese donors were analysed
      with the SNaPshot system to distinguish five known mutations (Se C357T, A385T,
      G428A, G716A and FUT1 880delTT) in the FUT1 and FUT2 genes. The genetic
      characteristics of all para-Bombay probands identified in the Fujian Blood
      Centre, including those in the present study, were also summarised. RESULTS:
      Three FUT1 genotypes, h1/h1 (5 individuals), h1/h6 (1 individual) and h3/h2 (1
      individual), and three FUT2 genotypes, Se(357)/Se(357) (5 individuals),
      Se(357)/Se(357, 385) (1 individual) and Se(357)/Se(357, 716) (1 individual) were
      observed in seven para-Bombay probands. Among 331 donors, only one individual
      carried the G716A and 880delTT mutations in heterozygosity; this subjects FUT1
      and FUT2 genotypes were H/h2 and Se(357)/Se(357, 716), respectively. CONCLUSION:
      The review of all para-Bombay probands identified in the Fujian Blood Centre
      showed that h1 and h2 are the predominant non-functional FUT1 alleles in Fujian
      para-Bombay individuals. Our data confirm the hypothesis that the h2 allele is
      linked to Se(357, 716), and the concurrence of unique FUT1 and FUT2 mutations is
      geographically specific.

PMID- 25761313
TI  - Complement-mediated haemolysis and the role of blood transfusion in paroxysmal
      nocturnal haemoglobinuria.

PMID- 25761314
TI  - Knowledge about umbilical cord blood donation: a survey-based study performed in
      Tuscany.

PMID- 25761315
TI  - Serological and molecular analyses of a patient with anti-G and anti-D due to
      alloimmunisation during her pregnancy.

PMID- 25761316
TI  - Transient transforming growth factor beta1 modulation in monocytes and natural
      killer cells following plasma or plasma-platelet apheresis donation procedures.

PMID- 25761317
TI  - Quantitation of Lan antigen in Lan+, Lan+(w) and Lan- phenotypes.

PMID- 25761318
TI  - The effect of dabigatran and rivarovaban on a prothrombinase-based assay for
      activated protein C resistance: a preliminary study in subjects heterozygous for
      factor V Leiden.

PMID- 25761319
TI  - Learn more to do better... even for participants in haemophilia clinical trials.

PMID- 25761320
TI  - Variability in splanchnic tissue oxygenation during preterm red blood cell
      transfusion given for symptomatic anaemia may reveal a potential mechanism of
      transfusion-related acute gut injury.
AB  - BACKGROUND: There is increasing evidence indicating an association between red
      blood cell (RBC) transfusions and necrotising enterocolitis (NEC) in preterm
      infants, especially late-onset NEC. This phenomenon is referred to as transfusion
      related acute gut injury (TRAGI). One theory as to a pathophysiological mechanism
      is that transfusion may result in an ischemia-reperfusion injury to intestinal
      tissue. We tested the hypothesis that there is significantly greater variability
      during transfusion in splanchnic tissue oxygen saturation (SrSO2) than in
      cerebral tissue oxygen saturation (CrSO2). MATERIALS AND METHODS: This was a
      prospective, observational study using near-infrared spectroscopy to monitor
      SrSO2 and CrSO2 in preterm neonates undergoing RBC transfusion for symptomatic
      anaemia. Mean, standard deviation, highest and lowest SrSO2 and CrSO2 values
      during each transfusion were determined. The greatest difference in SrSO2 and
      CrSO2 during each transfusion was calculated, along with the coefficient of
      variation. RESULTS: We studied 37 subjects. Throughout all transfusions, the mean
      SrSO2 was 45.6% +/-13.8 and the mean CrSO2 was 65.4% +/-6.9 (p<0.001). The
      variability of SrSO2 was significantly greater than that of CrSO2. Averaging data
      from all subjects, the greatest difference in SrSO2 was 43.8% +/-13.4 compared
      with 23.3% +/-7.6 for CrSO2 (p<0.001). The mean coefficient of variation in all
      transfusions was 20.5% for SrSO2 and 6.0% for CrSO2 (p<0.001). Increasing post
      conceptional age did not affect SrSO2 variability (R(2) =0.022; p=0.379), whereas
      CrSO2 variability during transfusion decreased with increasing post-conceptional
      age (R(2)=0.209; p=0.004). DISCUSSION: In preterm infants, there is a large
      degree of tissue oxygenation variability in splanchnic tissue during RBC
      transfusion and this does not change with increasing maturity. We speculate that
      these findings, combined with lower average tissue oxygenation, may demonstrate
      susceptibility of the preterm gut to TRAGI.

PMID- 25761321
TI  - Safety and efficacy of granulocyte colony-stimulating factor biosimilars in
      engraftment after autologous stem cell transplantation for haematological
      malignancies: a 4-year, single institute experience with different conditioning
      regimens.
AB  - BACKGROUND: Filgrastim biosimilars have recently been introduced into clinical
      practice. To date biosimilars have demonstrated comparable efficacy and safety as
      the originator in chemotherapy-induced neutropenia. Published experience in
      engraftment after autologous stem cell transplantation (ASCT) is limited and
      concerns relatively few patients. MATERIALS AND METHODS: With the aim of
      assessing the efficacy and the safety of filgrastim biosimilars in post-ASCT bone
      marrow recovery, we conducted a single institution, retrospective study in 56
      lymphoma and myeloma patients who received filgrastim biosimilars
      (Tevagrastim((r)) and Zarzio((r))) at standard doses from day 5. We compared our
      results with recently published data on the originator. A cost analysis of each
      biosimilar was performed. RESULTS: Neutrophil counts recovered in 55 patients.
      The median number of filgrastim biosimilar vials injected was seven per patient.
      The median time to neutrophil and platelet recovery was 10 and 12 days,
      respectively. Twenty-six patients had febrile neutropenia, in half of whom the
      agent involved was identified. In the cost analysis, the use of Tevagrastim((r))
      and Zarzio((r)) was associated with cost reductions of 56% and of 86%,
      respectively. DISCUSSION: Despite differences in CD34+ cell counts and time of
      starting filgrastim, our results in terms of time to engraftment and median
      number of vials injected are similar to published data. Comparing our results by
      single conditioning regimen to recent literature data, the time to engraftment
      and duration of hospitalisation were equivalent. Significant differences were
      observed in the incidence of febrile neutropenia, perhaps due to different
      preventive and prophylactic protocols for infections. Although prospective
      studies should be performed to confirm our results, filgrastim biosimilars were
      found to be effective and safe in engraftment after ASCT.

PMID- 25761322
TI  - Evaluation of nucleated red blood cell count by Sysmex XE-2100 in patients with
      thalassaemia or sickle cell anaemia and in neonates.
AB  - BACKGROUND: Current haematology analysers have variable sensitivity and accuracy
      for counting nucleated red blood cells in samples with low values and in all
      those conditions characterised by altered sensitivity of red blood cells to the
      lysing process, such as in beta-thalassaemia or sickle-cell diseases and in
      neonates. The aim of our study was to evaluate the performance of the automated
      analyser XE-2100 at counting nucleated red blood cells in the above-mentioned
      three categories of subjects with potentially altered red blood cell lysis
      sensitivity and yet a need for accurate nucleated red blood cell counts.
      MATERIALS AND METHODS: We measured nucleated red blood cell count by XE-2100 in
      peripheral blood samples of 187 subjects comprising 55 patients with beta
      thalassaemia (40 major and 15 traits), 26 sickle-cell patients, 56 neonates and
      50 normal subject. Results were compared with those obtained by optical
      microscopy. Agreement between average values of the two methods was estimated by
      means of Pearson's correlation and bias analysis, whereas diagnostic accuracy was
      estimated by analysis of receiver operating characteristic curves. RESULTS: The
      comparison between the two methods showed a Pearson's correlation of 0.99 (95%
      CI; 0.98-0.99; p<0.001) and bias of -0.61 (95% CI, -1.5-0.3). The area under the
      curve of the nucleated red blood cell count in all samples was 0.98 (95% CI, 0.96
      1.00; p<0.001). Sub-analysis revealed an area under curve of 0.99 (95% CI, 0.98
      1.00; p<0.001) for patients with thalassaemia, 0.94 (95% CI, 0.85-1.00; p<0.001)
      for patients with sickle cell anaemia, and 1.00 (95% CI, 1.0-1.0) for neonates.
      DISCUSSION: XE-2100 has excellent performance for nucleated red blood cell
      counting, especially in critical populations such as patients with
      haemoglobinopathies and neonates.

PMID- 25761323
TI  - Erroneous HLA typing as a result of acquired uniparental disomy in a patient with
      acute lymphoblastic leukaemia in peripheral blood complete remission.

PMID- 25761324
TI  - Use of a haemostatic matrix does not reduce blood loss in minimally invasive
      total knee arthroplasty.
AB  - BACKGROUND: Blood loss can increase morbidity and the risk of transfusion after
      total knee arthroplasty (TKA). This study evaluated the difference in blood loss
      between minimally invasive TKA performed with and without intra-articular use of
      a haemostatic matrix (Floseal(r)). MATERIALS AND METHODS: We retrospectively
      compared matched pairs in two groups (76 patients in each group): one group
      received conventional haemostasis (with bovie electrocoagulation), the other
      group was treated with an intra-articular haemostatic matrix (HM) as an adjunct
      to electrocoagulation. The outcomes compared were haemoglobin (Hb) and
      haematocrit levels at days 2 and 4 after surgery as a surrogate for blood loss,
      transfusion rate, surgical time, preoperative and postoperative range of motion
      (ROM) at days 21 and 42 and length of stay (LOS) in hospital. RESULTS: No
      differences were observed for Hb levels at day 2 or day 4 between men in the two
      groups. In women, however, the mean Hb at day 2 was 11.1 g/dL (SD 1.3) for TKA
      with HM and 12.0 g/dL (SD 0.9) for TKA without HM (p<0.001), while that at day 4
      was 10.6 g/dL (SD 1.3) for TKA with HM and 11.4 g/dL (SD 1.2) for TKA without HM
      (p<0.001). The haematocrit was higher for TKA without HM at day 2 (p=0.001) and
      day 4 (p=0.008). The transfusion rate for TKA with HM was 2.6% and for TKA
      without HM 0% (p=0.497), while the mean surgical time was 93 minutes (SD 12) vs
      87 minutes (SD 14), respectively (p=0.0055). There were no differences in
      preoperative or postoperative ROM at days 21 and 42 between the two groups. The
      LOS was longer for TKA with HM than for TKA without HM (4.5 days and 4 days,
      respectively, p=0.011) influenced by the longer stay for the transfused patients.
      DISCUSSION: The present study showed that the use of Floseal had no effect on
      reducing either visible or hidden blood loss after TKA, as assessed by a drop in
      Hb or haematocrit and that hidden blood loss was more important in women treated
      with the HM.

PMID- 25761325
TI  - ABO matching of platelet transfusions - "Start Making Sense". "As we get older,
      and stop making sense..." - The Talking Heads (1984).

PMID- 25761326
TI  - A fatal case of post-transfusion sepsis caused by Yersinia enterocolitica after
      delivery.

PMID- 25761327
TI  - The "Blood Apple Tree". A simple and straightforward metaphor for teaching blood
      and bone marrow physiology.

PMID- 25761329
TI  - Separable effects of inversion and contrast-reversal on face detection thresholds
      and response functions: a sweep VEP study.
AB  - The human brain rapidly detects faces in the visual environment. We recently
      presented a sweep visual evoked potential approach to objectively define face
      detection thresholds as well as suprathreshold response functions (Ales, Farzin,
      Rossion, & Norcia, 2012). Here we determined these parameters are affected by
      orientation (upright vs. inverted) and contrast polarity (positive vs. negative),
      two manipulations that disproportionately disrupt the perception of faces
      relative to other object categories. Face stimuli parametrically increased in
      visibility through phase-descrambling while alternating with scrambled images at
      a fixed presentation rate of 3 Hz (6 images/s). The power spectrum and mean
      luminance of all stimuli were equalized. As a face gradually emerged during a
      stimulation sequence, EEG responses at 3 Hz appeared at ~35% phase coherence over
      right occipito-temporal channels, replicating previous observations. With
      inversion and contrast-reversal, the 3-Hz amplitude decreased by ~20%-50% and the
      face detection threshold increased by ~30%-60% coherence. Furthermore, while the
      3-Hz response emerged abruptly and saturated quickly for normal faces, suggesting
      a categorical neural response, the response profile for inverted and negative
      polarity faces was shallower and more linear, indicating gradual and continuously
      increasing activation of the underlying neural population. These findings
      demonstrate that inversion and contrast-reversal increase the threshold and
      modulate the suprathreshold response function of face detection.

PMID- 25761328
TI  - Salience of unique hues and implications for color theory.
AB  - The unique hues--blue, green, yellow, red--form the fundamental dimensions of
      opponent-color theories, are considered universal across languages, and provide
      useful mental representations for structuring color percepts. However, there is
      no neural evidence for them from neurophysiology or low-level psychophysics.
      Tapping a higher prelinguistic perceptual level, we tested whether unique hues
      are particularly salient in search tasks. We found no advantage for unique hues
      over their nonunique complementary colors. However, yellowish targets were
      detected faster, more accurately, and with fewer saccades than their
      complementary bluish targets (including unique blue), while reddish-greenish
      pairs were not significantly different in salience. Similarly, local field
      potentials in primate V1 exhibited larger amplitudes and shorter latencies for
      yellowish versus bluish stimuli, whereas this effect was weaker for reddish
      versus greenish stimuli. Consequently, color salience is affected more by early
      neural response asymmetries than by any possible mental or neural representation
      of unique hues.

PMID- 25761330
TI  - Disentangling the effects of spatial inconsistency of targets and distractors
      when searching in realistic scenes.
AB  - Previous research has suggested that correctly placed objects facilitate eye
      guidance, but also that objects violating spatial associations within scenes may
      be prioritized for selection and subsequent inspection. We analyzed the
      respective eye guidance of spatial expectations and target template (precise
      picture or verbal label) in visual search, while taking into account any impact
      of object spatial inconsistency on extrafoveal or foveal processing. Moreover, we
      isolated search disruption due to misleading spatial expectations about the
      target from the influence of spatial inconsistency within the scene upon search
      behavior. Reliable spatial expectations and precise target template improved
      oculomotor efficiency across all search phases. Spatial inconsistency resulted in
      preferential saccadic selection when guidance by template was insufficient to
      ensure effective search from the outset and the misplaced object was bigger than
      the objects consistently placed in the same scene region. This prioritization
      emerged principally during early inspection of the region, but the inconsistent
      object also tended to be preferentially fixated overall across region viewing.
      These results suggest that objects are first selected covertly on the basis of
      their relative size and that subsequent overt selection is made considering
      object-context associations processed in extrafoveal vision. Once the object was
      fixated, inconsistency resulted in longer first fixation duration and longer
      total dwell time. As a whole, our findings indicate that observed impairment of
      oculomotor behavior when searching for an implausibly placed target is the
      combined product of disruption due to unreliable spatial expectations and
      prioritization of inconsistent objects before and during object fixation. 

PMID- 25761331
TI  - Perception of physical stability and center of mass of 3-D objects.
AB  - Humans can judge from vision alone whether an object is physically stable or not.
      Such judgments allow observers to predict the physical behavior of objects, and
      hence to guide their motor actions. We investigated the visual estimation of
      physical stability of 3-D objects (shown in stereoscopically viewed rendered
      scenes) and how it relates to visual estimates of their center of mass (COM). In
      Experiment 1, observers viewed an object near the edge of a table and adjusted
      its tilt to the perceived critical angle, i.e., the tilt angle at which the
      object was seen as equally likely to fall or return to its upright stable
      position. In Experiment 2, observers visually localized the COM of the same set
      of objects. In both experiments, observers' settings were compared to physical
      predictions based on the objects' geometry. In both tasks, deviations from
      physical predictions were, on average, relatively small. More detailed analyses
      of individual observers' settings in the two tasks, however, revealed mutual
      inconsistencies between observers' critical-angle and COM settings. The results
      suggest that observers did not use their COM estimates in a physically correct
      manner when making visual judgments of physical stability. 

PMID- 25761332
TI  - Perceptual biases and cue weighting in perception of 3D slant from texture and
      stereo information.
AB  - Multiple cues are typically available for perceiving the 3D slant of surfaces,
      and slant perception has been used as a test case for investigating cue
      integration. Previous evidence suggests that texture and stereo slant cues
      contribute in an optimal Bayesian manner. We tested whether a Bayesian model
      could also account for perceptual underestimation of slant from texture. One
      explanation proposed by Todd, Christensen, and Guckes (2010) is that slant from
      texture is based on an inaccurate optical variable. An alternative Bayesian
      explanation is that perceptual underestimation is due to the influence of frontal
      cues and/or a frontal prior, which is weighted according to the reliability of
      slant cues. We measured slant perception using a hand-alignment task for
      conditions that provided only texture, only stereo, or combined texture and
      stereo cues. Slant estimates from monocular texture showed large biases toward
      frontal, with proportionally more underestimation at low slants than high slants.
      Slant estimates from stereo alone were more accurate, and adding texture
      information did not reduce accuracy. These results are consistent with a frontal
      influence that is decreasingly weighted as slant information becomes more
      reliable. We also included conditions with small cue conflicts to measure the
      relative weighting of texture and stereo cues. Consistent with previous studies,
      texture had a significant effect on slant estimates in binocular conditions, and
      the relative weighting of texture increased with slant. In some cases, perceived
      slant from combined stereo and texture cues was higher than from either cue in
      isolation. Both the perceptual biases and the cue weights were generally
      consistent with a Bayesian model that optimally integrates texture and stereo
      slant cues with frontal cues and/or a frontal prior. 

PMID- 25761333
TI  - Letter identification and the neural image classifier.
AB  - Letter identification is an important visual task for both practical and
      theoretical reasons. To extend and test existing models, we have reviewed
      published data for contrast sensitivity for letter identification as a function
      of size and have also collected new data. Contrast sensitivity increases rapidly
      from the acuity limit but slows and asymptotes at a symbol size of about 1
      degree. We recast these data in terms of contrast difference energy: the average
      of the squared distances between the letter images and the average letter image.
      In terms of sensitivity to contrast difference energy, and thus visual
      efficiency, there is a peak around 1/4 degree, followed by a marked decline at
      larger sizes. These results are explained by a Neural Image Classifier model that
      includes optical filtering and retinal neural filtering, sampling, and noise,
      followed by an optimal classifier. As letters are enlarged, sensitivity declines
      because of the increasing size and spacing of the midget retinal ganglion cell
      receptive fields in the periphery. 

PMID- 25761335
TI  - Evidence for parallel consolidation of motion direction and orientation into
      visual short-term memory.
AB  - Recent findings have indicated the capacity to consolidate multiple items into
      visual short-term memory in parallel varies as a function of the type of
      information. That is, while color can be consolidated in parallel, evidence
      suggests that orientation cannot. Here we investigated the capacity to
      consolidate multiple motion directions in parallel and reexamined this capacity
      using orientation. This was achieved by determining the shortest exposure
      duration necessary to consolidate a single item, then examining whether two
      items, presented simultaneously, could be consolidated in that time. The results
      show that parallel consolidation of direction and orientation information is
      possible, and that parallel consolidation of direction appears to be limited to
      two. Additionally, we demonstrate the importance of adequate separation between
      feature intervals used to define items when attempting to consolidate in
      parallel, suggesting that when multiple items are consolidated in parallel, as
      opposed to serially, the resolution of representations suffer. Finally, we used
      facilitation of spatial attention to show that the deterioration of item
      resolution occurs during parallel consolidation, as opposed to storage. 

PMID- 25761334
TI  - Different time scales of motion integration for anticipatory smooth pursuit and
      perceptual adaptation.
AB  - When repeatedly exposed to moving stimuli, the oculomotor system elicits
      anticipatory smooth pursuit (ASP) eye movements, even before the stimulus moves.
      ASP is affected oppositely to perceptual speed judgments of repetitive moving
      stimuli: After a sequence of fast stimuli, ASP velocity increases, whereas
      perceived speed decreases. These two effects--perceptual adaptation and
      oculomotor priming--could result from adapting a single common internal speed
      representation that is used for perceptual comparisons and for generating ASP.
      Here we test this hypothesis by assessing the temporal dependence of both effects
      on stimulus history. Observers performed speed discriminations on moving random
      dot stimuli, either while pursuing the movement or maintaining steady fixation.
      In both cases, responses showed perceptual adaptation: Stimuli preceded by fast
      speeds were perceived as slower, and vice versa. To evaluate oculomotor priming,
      we analyzed ASP velocity as a function of average stimulus speed in preceding
      trials and found strong positive dependencies. Interestingly, maximal priming
      occurred over short stimulus histories (~two trials), whereas adaptation was
      maximal over longer histories (~15 trials). The temporal dissociation of
      adaptation and priming suggests different underlying mechanisms. It may be that
      perceptual adaptation integrates over a relatively long period to robustly
      calibrate the operating range of the motion system, thereby avoiding interference
      from transient changes in stimulus speed. On the other hand, the oculomotor
      system may rapidly prime anticipatory velocity to efficiently match it to that of
      the pursuit target.

PMID- 25761336
TI  - Numerosity and density judgments: biases for area but not for volume.
AB  - Human observers can rapidly judge the number of items in a scene. This ability is
      underpinned by specific mechanisms encoding number or density. We investigated
      whether judgments of number and density are biased by a change in volume, as they
      are by a change in area. Stimuli were constructed using nonoverlapping black and
      white luminance-defined dots. An eight-mirror Wheatstone stereoscope was used to
      present the dots as though in a volume. Using a temporal two-alternative forced
      choice (2AFC) task and the Method of Constant Stimuli (MOCS), we measured the
      precision and bias (PSE shift) of numerosity and density judgments, separately,
      for stimuli differing in area or volume. For two-dimensional (2-D) stimuli,
      consistent with previous literature, perceived density was biased as area
      increased. However, perceived number was not. For three-dimensional (3-D)
      stimuli, despite a vivid impression of the dots filling a cylindrical volume,
      there was no bias in perceived density or number as volume increased. A control
      experiment showed that all of our observers could easily perceive disparity in
      our stimuli. Our findings reveal that number and density judgments that are
      biased by area are not similarly biased by volume changes. 

PMID- 25761338
TI  - Gaze direction affects the magnitude of face identity aftereffects.
AB  - The face perception system partly owes its efficiency to adaptive mechanisms that
      constantly recalibrate face coding to our current diet of faces. Moreover, faces
      that are better attended produce more adaptation. Here, we investigated whether
      the social cues conveyed by a face can influence the amount of adaptation that
      face induces. We compared the magnitude of face identity aftereffects induced by
      adaptors with direct and averted gazes. We reasoned that faces conveying direct
      gaze may be more engaging and better attended and thus produce larger
      aftereffects than those with averted gaze. Using an adaptation duration of 5 s,
      we found that aftereffects for adaptors with direct and averted gazes did not
      differ (Experiment 1). However, when processing demands were increased by
      reducing adaptation duration to 1 s, we found that gaze direction did affect the
      magnitude of the aftereffect, but in an unexpected direction: Aftereffects were
      larger for adaptors with averted rather than direct gaze (Experiment 2). Eye
      tracking revealed that differences in looking time to the faces between the two
      gaze directions could not account for these findings. Subsequent ratings of the
      stimuli (Experiment 3) showed that adaptors with averted gaze were actually
      perceived as more expressive and interesting than adaptors with direct gaze.
      Therefore it appears that the averted-gaze faces were more engaging and better
      attended, leading to larger aftereffects. Overall, our results suggest that
      naturally occurring facial signals can modulate the adaptive impact a face exerts
      on our perceptual system. Specifically, the faces that we perceive as most
      interesting also appear to calibrate the organization of our perceptual system
      most strongly. 

PMID- 25761337
TI  - Individual differences in visual field shape modulate the effects of attention on
      the lower visual field advantage in crowding.
AB  - It has previously been reported that visual crowding of a target by flankers is
      stronger in the upper visual field than in the lower, and this finding has been
      attributed to greater attentional resolution in the lower hemifield (He,
      Cavanagh, & Intriligator, 1996). Here we show that the upper/lower asymmetry in
      visual crowding can be explained by natural variations in the borders of each
      individual's visual field. Specifically, asymmetry in crowding along the vertical
      meridian can be almost entirely accounted for by replacing the conventional
      definition of visual field location, in units of degrees of visual angle, with a
      definition based on the ratio of the extents of an individual's upper and lower
      visual field. We also show that the upper/lower crowding asymmetry is eliminated
      when stimulus eccentricity is expressed in units of percentage of visual field
      extent but is present when the conventional measure of visual angle is used. We
      further demonstrate that the relationship between visual field extent and
      perceptual asymmetry is most evident when participants are able to focus their
      attention on the target location. These results reveal important influences of
      visual field boundaries on visual perception, even for visual field locations far
      from those boundaries. 

PMID- 25761339
TI  - Contextual factors modulate concurrent planning of sequential saccades.
AB  - Natural vision typically involves making multiple eye movements to interpret
      complex visual scenes. Although previous work has shown that individual saccadic
      end points are modulated by cognitive context, whether and how contextual factors
      quantitatively influence the planning of sequential saccades is still unclear. We
      compared performance of subjects in a modified double-step task under different
      task instructions (FOLLOW vs. REDIRECT; Ray, Schall, & Murthy, 2004) as well as
      task structure (40% and 100% FOLLOW). The results support the idea of restricted
      concurrent preparation when the second saccade was part of the sequence as per
      task demands as opposed to being inadvertently made following an error. Also,
      increasing the probability of double-target trials in the task (100% vs. 40%
      FOLLOW) tended to enhance concurrent planning even when the serial order of
      saccades continued to remain important. Taken together, these data reveal how the
      concurrent planning of sequential saccades can be contextually regulated by means
      of task instruction and trial statistics. 

PMID- 25761340
TI  - The effects of smooth occlusions and directions of illumination on the visual
      perception of 3-D shape from shading.
AB  - Human observers made local orientation judgments of smoothly shaded surfaces
      illuminated from different directions by large area lights, both with and without
      visible smooth occlusion contours. Test-retest correlations between the first and
      second halves of the experiment revealed that observers' judgments were highly
      reliable, with a residual error of only 2%. Over 88% of the variance between
      observers' judgments and the simulated objects could be accounted for by an
      affine correlation, but there was also a systematic nonaffine component that
      accounted for approximately 10% of the perceptual error. The presence or absence
      of visible smooth occlusion contours had a negligible effect on performance, but
      there was a small effect of the illumination direction, such that the response
      surfaces were sheared slightly toward the light source. These shearing effects
      were much smaller, however, than the effects produced by changes in illumination
      on the overall pattern of luminance or luminance gradients. Implications of these
      results for current models of estimating 3-D shape from shading are considered. 

PMID- 25761342
TI  - Can walking motions improve visually induced rotational self-motion illusions in
      virtual reality?
AB  - Illusions of self-motion (vection) can provide compelling sensations of moving
      through virtual environments without the need for complex motion simulators or
      large tracked physical walking spaces. Here we explore the interaction between
      biomechanical cues (stepping along a rotating circular treadmill) and visual cues
      (viewing simulated self-rotation) for providing stationary users a compelling
      sensation of rotational self-motion (circular vection). When tested individually,
      biomechanical and visual cues were similarly effective in eliciting self-motion
      illusions. However, in combination they yielded significantly more intense self
      motion illusions. These findings provide the first compelling evidence that
      walking motions can be used to significantly enhance visually induced rotational
      self-motion perception in virtual environments (and vice versa) without having to
      provide for physical self-motion or motion platforms. This is noteworthy, as
      linear treadmills have been found to actually impair visually induced
      translational self-motion perception (Ash, Palmisano, Apthorp, & Allison, 2013).
      Given the predominant focus on linear walking interfaces for virtual-reality
      locomotion, our findings suggest that investigating circular and curvilinear
      walking interfaces offers a promising direction for future research and
      development and can help to enhance self-motion illusions, presence and immersion
      in virtual-reality systems. 

PMID- 25761343
TI  - The use of higher-order statistics in rapid object categorization in natural
      scenes.
AB  - We can rapidly and efficiently recognize many types of objects embedded in
      complex scenes. What information supports this object recognition is a
      fundamental question for understanding our visual processing. We investigated the
      eccentricity-dependent role of shape and statistical information for ultrarapid
      object categorization, using the higher-order statistics proposed by Portilla and
      Simoncelli (2000). Synthesized textures computed by their algorithms have the
      same higher-order statistics as the originals, while the global shapes were
      destroyed. We used the synthesized textures to manipulate the availability of
      shape information separately from the statistics. We hypothesized that shape
      makes a greater contribution to central vision than to peripheral vision and that
      statistics show the opposite pattern. Results did not show contributions clearly
      biased by eccentricity. Statistical information demonstrated a robust
      contribution not only in peripheral but also in central vision. For shape, the
      results supported the contribution in both central and peripheral vision. Further
      experiments revealed some interesting properties of the statistics. They are
      available for a limited time, attributable to the presence or absence of animals
      without shape, and predict how easily humans detect animals in original images.
      Our data suggest that when facing the time constraint of categorical processing,
      higher-order statistics underlie our significant performance for rapid
      categorization, irrespective of eccentricity. 

PMID- 25761341
TI  - Estimation of cortical magnification from positional error in normally sighted
      and amblyopic subjects.
AB  - We describe a method for deriving the linear cortical magnification factor from
      positional error across the visual field. We compared magnification obtained from
      this method between normally sighted individuals and amblyopic individuals, who
      receive atypical visual input during development. The cortical magnification
      factor was derived for each subject from positional error at 32 locations in the
      visual field, using an established model of conformal mapping between retinal and
      cortical coordinates. Magnification of the normally sighted group matched
      estimates from previous physiological and neuroimaging studies in humans,
      confirming the validity of the approach. The estimate of magnification for the
      amblyopic group was significantly lower than the normal group: by 4.4 mm deg(-1)
      at 1 degrees  eccentricity, assuming a constant scaling factor for both groups.
      These estimates, if correct, suggest a role for early visual experience in
      establishing retinotopic mapping in cortex. We discuss the implications of
      altered cortical magnification for cortical size, and consider other neural
      changes that may account for the amblyopic results. 

PMID- 25761344
TI  - Aging effects in cueing tasks as assessed by the ideal observer: peripheral cues.
AB  - Previous aging and cueing studies suggest that automatic orienting driven by
      peripheral cues is preserved with aging; however, inconsistencies can be found.
      One issue might be the use of response times (RT) to assess cueing effects
      (invalid RT--valid RT), which, in many cases, may not have clear quantitative
      predictions. We propose an ideal observer (IO) analysis of accuracy estimating
      participants' internal value of cue validity, or weight, which should equal the
      actual cue validity. The weight measures the use of information provided by the
      cue and is insensitive to variations in set size and difficulty, thus potentially
      providing advantages to RT. Older (n = 54) and younger (n = 58) participants
      performed a yes/no detection task of a two-dimensional (2-D) Gaussian (60 ms).
      Square peripheral precues (150 ms) indicated likely target locations (70% valid)
      across two or six locations (set sizes). For cueing effects, (valid--invalid hit
      rates), younger participants had set-size effects (larger cueing effects for set
      size 6), while older participants did not. The opposite pattern was found for
      weights (younger: no set-size effects, older: set-size effects) due to the IO
      predicting larger cueing effects for larger set sizes. Comparisons to the ideal
      weight (cue validity) suggested that older participants used the cue information
      effectively with set size 2 (as or more so than younger participants), but not
      with set size 6. These results suggest that attentional deficits from aging in
      peripheral cueing tasks may only arise as difficulty increases, such as larger
      set sizes.

PMID- 25761345
TI  - Saccadic distractor effects: the remote distractor effect (RDE) and saccadic
      inhibition (SI): A response to McIntosh and Buonocore (2014).
AB  - We (Walker & Benson, 2013) reported studies in which the spatial effects of
      distractors on the remote distractor effect (RDE) and saccadic inhibition (SI)
      were examined. Distractors remote from the target increased mean latency and the
      skew of the distractor-related distributions, without the presence of dips that
      are regarded as the hallmark of SI. We further showed that early onset
      distractors had similar effects although these would not be consistent with
      existing estimates of the duration of SI (of around 60-70 ms). McIntosh and
      Buonocore (2014) report a simulation showing that skewed latency distributions
      can arise from the putative SI mechanism and they also highlighted a number of
      methodological considerations regarding the RDE and SI as measures of saccadic
      distractor effects (SDEs). Here we evaluate these claims and note that the
      measures of SI obtained by subtracting latency distributions (specifically the
      decrease in saccade frequency--or dip duration) are no more diagnostic of a
      single inhibitory process, or more sensitive indicators of it, than is median
      latency. Furthermore the evidence of inhibitory influences of small distractors
      presented close to the target is incompatible with the explanations of both the
      RDE and SI. We conclude that saccadic distractor effects may be a more inclusive
      term to encompass the different characteristics of behavioral effects of
      underlying saccade target selection.

PMID- 25761346
TI  - Left visual field attentional advantage in judging simultaneity and temporal
      order.
AB  - Dynamic environments often contain features that vary simultaneously as well as
      features that vary sequentially. In principle, the correspondingly distinct
      sensations of simultaneity and temporal order could arise from a single shared
      neural computation that involves differencing two arrival times. On the other
      hand, simultaneity judgments (SJs) and temporal order judgments (TOJs) have
      distinct informational requirements that could be optimized by distinct neural
      events. To explore overlap in the neural events mediating SJs and TOJs, the
      present experiments built on recent reports that SJ precision in the left visual
      field (LVF) exceeds that in the right visual field (RVF). Participants completed
      divided attention tasks requiring either SJs or TOJs to LVF or RVF targets. SJs
      exhibited a significant LVF advantage, as expected. TOJs also exhibited a
      significant LVF advantage. Specifically, simply repositioning targets from the
      LVF to the RVF generated mean TOJ threshold increases (temporal precision
      reductions) between 39% and 57%, an effect size equivalent to approximately two
      LVF detectors for each RVF detector. Control experiments indicated that this LVF
      advantage reflected the temporal resolution of visual attention, rather than
      lower-level flicker discrimination or masking. These findings constitute
      additional evidence for an LVF advantage in time-sensitive attentional tasks and
      further contradict our subjective experience of homogenous temporal precision
      across the visual field. 

PMID- 25761347
TI  - Evolving the stimulus to fit the brain: a genetic algorithm reveals the brain's
      feature priorities in visual search.
AB  - How does the brain find objects in cluttered visual environments? For decades
      researchers have employed the classic visual search paradigm to answer this
      question using factorial designs. Although such approaches have yielded important
      information, they represent only a tiny fraction of the possible parametric
      space. Here we use a novel approach, by using a genetic algorithm (GA) to
      discover the way the brain solves visual search in complex environments, free
      from experimenter bias. Participants searched a series of complex displays, and
      those supporting fastest search were selected to reproduce (survival of the
      fittest). Their display properties (genes) were crossed and combined to create a
      new generation of "evolved" displays. Displays evolved quickly over generations
      towards a stable, efficiently searched array. Color properties evolved first,
      followed by orientation. The evolved displays also contained spatial patterns
      suggesting a coarse-to-fine search strategy. We argue that this behavioral
      performance-driven GA reveals the way the brain selects information during visual
      search in complex environments. We anticipate that our approach can be adapted to
      a variety of sensory and cognitive questions that have proven too intractable for
      factorial designs. 

PMID- 25761348
TI  - Perceptual biases are inconsistent with Bayesian encoding of speed in the human
      visual system.
AB  - The notion that Bayesian processes are fundamental to brain function and sensory
      processing has recently received much support, and a number of Bayesian accounts
      of how the brain encodes the speed of moving objects have been proposed that
      challenge earlier mechanistic models. We measured the perceived speed of low
      contrast patterns at both low (2.5 cd m(-2)) and high (25 cd m(-2)) luminance in
      order to assess these competing models of how the human visual system encodes
      speed. At both luminance levels low contrast stimuli are perceptually biased such
      that they appear slower at slow (< 8 Hz) speeds but faster at higher (16 Hz)
      speeds. However, we find that the reversal of the perceptual bias from under- to
      overestimation occurred at slower speeds at low luminance. We also found that the
      bias was greater at slow speeds at high luminance but greater at fast speeds at
      low luminance. Moreover, discrimination thresholds were found to be similar at
      high and low luminance. These findings can be predicted by models in which speed
      is encoded by the relative activity within two broadly tuned temporal channels
      but are inconsistent with Bayesian models of speed encoding. We conclude that
      Bayesian processes cannot adequately account for speed encoding in the human
      visual system. 

PMID- 25761349
TI  - Saccade kinematics modulate perisaccadic perception.
AB  - Around the time of execution of an eye movement, participants systematically
      misperceive the spatial location of briefly flashed visual stimuli. This
      phenomenon, known as perisaccadic mislocalization, is thought to involve an
      active process that takes into account the motor plan (efference copy) of the
      upcoming saccade. While it has been proposed that the motor system anticipates
      and informs the visual system about the upcoming eye movements, at present the
      type and detail of information carried by this motor signal remains unclear. Some
      authors have argued that the efference copy conveys only coarse information about
      the direction of the eye movement, while a second theoretical view proposes that
      it provides specific details about the direction, amplitude, and velocity of the
      saccade to come. To test between these alternatives, we investigated the
      influence of saccade parameters on a perisaccadic unmasking task in which
      performance in discriminating the identity of a target (face or house) followed
      by a trailing mask is dramatically improved around the time of saccade onset. We
      found that the amplitude and peak velocity of the upcoming saccade modulated
      target perception, even for stimuli presented well before saccadic onset. We
      developed a predictive model for the generation of the efference copy that
      incorporates both saccade amplitude and saccade velocity planning prior to
      saccade execution. Overall, these results suggest that the efference copy stores
      specific information about the parameters of upcoming eye movement and that these
      parameters influence perception even prior to saccade onset. 

PMID- 25761350
TI  - [One airway, one disease].

PMID- 25761351
TI  - [Current topics of treatment for mental disease and suicide prevention in Japan].

PMID- 25761352
TI  - [Substance related disorders and addictive disorders].

PMID- 25761353
TI  - [Metabolic syndrome and depression].

PMID- 25761354
TI  - In memoriam: Skipper Poehlman.

PMID- 25761355
TI  - [Sexual dysfunction, gender identity disorders, paraphilic disorders].

PMID- 25761357
TI  - Evidence appraisal of Kadry B, Press CD, Alosh H, et al. Obesity increases
      operating room times in patients undergoing primary hip arthroplasty: a
      retrospective cohort analysis.: PeerJ. 2014;2:e530.

PMID- 25761356
TI  - Reply to the letter to the editor concerning the article: Figueiredo J, Santos A,
      Clemente H, Lourenco A, Costa S, Gracio MA, Belo S. Schistosomiasis and acute
      appendicitis. Acta Med Port. 2014;27:396-9.

PMID- 25761358
TI  - Using medical interpreters to provide  culturally competent care.

PMID- 25761359
TI  - Standardizing the OR to PACU patient  hand over.

PMID- 25761360
TI  - The importance of correct compounding  practices.

PMID- 25761362
TI  - Biophysical methods in cell biology. Preface.

PMID- 25761361
TI  - Amphiaraos of Attica: the "Second Asclepius".
AB  - Amphiaraos is one of the most prominent Greek heroes. He was the son of god
      Apollo and student of Centaur Chiron from whom he learned the art of medicine. He
      was thought to be the "Second Asclepius" and he had many sanctuaries around
      Greece of which the most well known is the Amphiaraeion of Oropos, near Athens.
      The aim of this study is to present the genealogical tree and life of Amphiaraos,
      as well as the methods used in his sanctuaries in order to offer cure in the ill
      pilgrims.

PMID- 25761363
TI  - High-performance hybrid buffer layer using 1,4,5,8,9,11
      hexaazatriphenylenehexacarbonitrile/molybdenum oxide in inverted top-emitting
      organic light-emitting diodes.
AB  - A high-performance 1,4,5,8,9,11-hexaazatriphenylenehexacarbonitrile
      (HATCN)/molybdenum oxide (MoO3) hybrid buffer layer with high hole-injection
      efficiency and superior plasma resistance under the sputtering process was
      developed. The HATCN enhances the hole-injection efficiency, and the MoO3
      effectively protects the underlying organic layers from plasma damage during
      deposition by sputtering. This improves the characteristics of inverted top
      emitting organic light-emitting diodes using a top transparent conductive oxide
      electrode. The device using the hybrid buffer layer showed the highest
      electroluminescence characteristics among devices with other buffer layers. The
      high hole-injection efficiency of HATCN was shown by the J-F curve of hole-only
      devices, and the plasma protection performance of MoO3 was shown by atomic force
      microscope surface morphology images of the buffer layer film after O2 plasma
      treatment. 

PMID- 25761364
TI  - Taiwanese farm workers' pesticide knowledge, attitudes, behaviors and clothing
      practices.
AB  - The purpose of this study was to assess Taiwanese fruit farm workers' knowledge,
      attitudes, behaviours, and clothing practices regarding pesticide activities.
      Seventy-seven fruit farm workers from four districts of Tainan City, Taiwan
      completed the questionnaire. Results indicated that farmer workers had a good
      overall level of knowledge of the adverse effects of pesticides on human health
      and most had experienced symptoms of pesticide poisoning. Farm workers' attitudes
      toward pesticide use and handling indicated that they saw pesticides useful in
      controlling pests. Farm workers indicated the limited availability of comfortable
      clothing designed for a hot and humid climate while still providing sufficient
      protection was the main reason for not wearing personal protective clothing (PPC)
      and personal protective equipment (PPE). Emphasis on safety precautions is needed
      when using pesticides, and the importance of PPC and PPE is essential for the
      health of farm workers. 

PMID- 25761365
TI  - Integration of computational modeling with membrane transport studies reveals new
      insights into amino acid exchange transport mechanisms.
AB  - Uptake of system L amino acid substrates into isolated placental plasma membrane
      vesicles in the absence of opposing side amino acid (zero-trans uptake) is
      incompatible with the concept of obligatory exchange, where influx of amino acid
      is coupled to efflux. We therefore hypothesized that system L amino acid exchange
      transporters are not fully obligatory and/or that amino acids are initially
      present inside the vesicles. To address this, we combined computational modeling
      with vesicle transport assays and transporter localization studies to investigate
      the mechanisms mediating [(14)C]L-serine (a system L substrate) transport into
      human placental microvillous plasma membrane (MVM) vesicles. The carrier model
      provided a quantitative framework to test the 2 hypotheses that l-serine
      transport occurs by either obligate exchange or nonobligate exchange coupled with
      facilitated transport (mixed transport model). The computational model could only
      account for experimental [(14)C]L-serine uptake data when the transporter was not
      exclusively in exchange mode, best described by the mixed transport model. MVM
      vesicle isolates contained endogenous amino acids allowing for potential
      contribution to zero-trans uptake. Both L-type amino acid transporter (LAT)1 and
      LAT2 subtypes of system L were distributed to MVM, with L-serine transport
      attributed to LAT2. These findings suggest that exchange transporters do not
      function exclusively as obligate exchangers.

PMID- 25761366
TI  - Selective biochemical labeling of Campylobacter jejuni cell-surface
      glycoconjugates.
AB  - The display of cell-surface glycolipids and glycoproteins is essential for the
      motility, adhesion and colonization of pathogenic bacteria such as Campylobacter
      jejuni. Recently, the cell-surface display of C. jejuni glycoconjugates has been
      the focus of considerable attention; however, our understanding of the roles that
      glycosylation plays in bacteria still pales in comparison with our understanding
      of mammalian glycosylation. One of the reasons for this is that carbohydrate
      metabolic labeling, a powerful tool for studying mammalian glycans, is difficult
      to establish in bacterial systems and has a significantly more limited scope.
      Herein, we report the development of an alternative strategy that can be used to
      study bacterial cell-surface glycoconjugates. Galactose oxidase (GalO) is used to
      generate an aldehyde at C-6 of terminal GalNAc residues of C. jejuni glycans.
      This newly generated aldehyde can be conjugated with aminooxy-functionalized
      purification tags or fluorophores. The label can be targeted towards specific
      glycoconjugates using C. jejuni mutant strains with N-glycan or lipo
      oligosaccharides (LOS) assembly defects. GalO-catalyzed labeling of cell-surface
      glycoproteins with biotin, allowed for the purification and identification of
      known extracellular N-linked glycoproteins as well as a recently identified O
      linked glycan modifying PorA. To expand the scope of the GalO reaction, live-cell
      fluorescent labeling of C. jejuni was used to compare the levels of surface
      exposed LOS to the levels of N-glycosylated, cell-surface proteins. While this
      study focuses on the GalO-catalyzed labeling of C. jejuni, it can in principle be
      used to evaluate glycosylation patterns and identify glycoproteins of interest in
      any bacteria. 

PMID- 25761367
TI  - Mannitol versus hypertonic saline: Safety and efficacy of mannitol and hypertonic
      saline in sputum induction and bronchial hyperreactivity assessment.
AB  - Eosinophilic asthma phenotype predicts good response to corticosteroids and
      associates to asthmatic exacerbations. Sputum induction by hypertonic saline (HS)
      inhalation is technically demanding. Bronchial hyperresponsiveness (BHR) to
      osmotic agents indirectly mirrors active airway inflammation. We compared the
      safety and ability of HS and mannitol to induce sputum and measure BHR. We
      evaluated the stability of inflammatory phenotypes. We studied 35 non-smoking
      asthmatics randomized to undergo HS and mannitol challenges on 2 days 1 week
      apart. Sputum was sampled for cell analysis and phenotyped as eosinophilic (>=3%
      eosinophils) and non-eosinophilic (<3%) asthma. Nineteen subjects had BHR to
      mannitol and nine of them also had BHR to HS. Drops in forced expiratory volume
      in 1 s were higher from HS challenge than from mannitol challenge. Adequate
      sputum samples were obtained from 80% subjects (68% mannitol and 71% HS).
      Eosinophils and macrophages from both challenges correlated. Neutrophils were
      higher in sputum from HS. Ninety percent samples were equally phenotyped with HS
      and mannitol. Fractional exhaled nitric oxide, sputum eosinophils and BHR
      correlated in both challenges. HS and mannitol showed similar capacity to produce
      valuable sputum samples. BHR to both osmotic stimuli partially resembled airway
      eosinophilic inflammation but mannitol was more sensitive than HS to assess BHR.
      Eosinophilic phenotype remained stable in most patients with both stimuli. 

PMID- 25761369
TI  - Postfracture pain in children can be adequately managed with ibuprofen.

PMID- 25761370
TI  - Inhibition of ABCA1 protein degradation promotes HDL cholesterol efflux capacity
      and RCT and reduces atherosclerosis in mice.
AB  - ABCA1 plays a key role in the initial lipidation of apoA-I, which generates
      circulating HDL cholesterol. Whereas it is known that the transcriptional
      upregulation of ABCA1 promotes HDL formation and reverse cholesterol transport
      (RCT), it is not known how the inhibition of ABCA1 protein degradation impacts
      HDL function. Employing the small molecule triacetyl-3-hydroxyphenyladenosine
      (IMM-H007), we determined how the attenuation of ABCA1 protein degradation
      affects HDL cholesterol efflux capacity, RCT, and atherosclerotic lesion
      formation. Pulse-chase analysis revealed that IMM-H007 inhibits ABCA1 degradation
      and facilitates its cell-surface localization in macrophages, and additional
      studies in macrophages showed that IMM-H007 thereby promotes cholesterol efflux.
      IMM-H007 treatment of Paigen diet-fed mice caused an increase in circulating HDL
      level, it increased the cholesterol efflux capacity of HDL, and it enhanced in
      vivo RCT from macrophages to the plasma, liver, and feces. Furthermore, ABCA1
      degradation suppression by IMM-H007 reduced atherosclerotic plaque formation in
      apoE(-/-) mice. Thus, via effects on both ABCA1-expressing cells and circulating
      HDL function, the inhibition of ABCA1 protein degradation by IMM-H007 promotes
      HDL cholesterol efflux capacity and RCT and attenuates atherogenesis. IMM-H007
      potentially represents a lead compound for the development of agents to augment
      HDL function. 

PMID- 25761371
TI  - Noninvasive assessment of macrovesicular liver steatosis in cadaveric donors
      based on computed tomography liver-to-spleen attenuation ratio.
AB  - Fatty liver disease, including liver steatosis, is a major health problem
      worldwide. In liver transplantation, macrovesicular steatosis in donor livers is
      a major cause of graft failure and remains difficult to assess. On one hand,
      several imaging modalities can be used for the assessment of liver fat, but liver
      biopsy, which is still considered the gold standard, may be difficult to perform
      in this context. On the other hand, computed tomography (CT) is commonly used by
      teams managing cadaveric donors to assess donors and to minimize the risk of
      complications in recipients. The purpose of our study was to validate the use of
      CT as a semiquantitative method for assessing macrovesicular steatosis in
      cadaveric donors with liver biopsy as a reference standard. A total of 109
      consecutive cadaveric donors were included between October 2009 and May 2011.
      Brain death was diagnosed according to French legislation. Liver biopsy and then
      CT were performed on the same day to determine the degree of macrovesicular
      steatosis. All liver biopsies and CT scans were analyzed in a double-blinded
      fashion by a senior pathologist and a senior radiologist, respectively. For CT,
      we used the liver-to-spleen (L/S) attenuation ratio, which is a validated method
      for determining 30% or greater steatosis in living liver donors. Fourteen of 109
      biopsies exhibited macrovesicular steatosis > 30% upon histologic analysis. A
      receiver operating characteristic curve was generated for the L/S ratio to
      identify its ability to predict significant steatosis, which was defined as >30%.
      A cutoff value of 0.9 for the CT L/S ratio provided a sensitivity of 79% and a
      specificity of 97% to detect significant steatosis.

PMID- 25761368
TI  - Cellular responses to a prolonged delay in mitosis are determined by a DNA damage
      response controlled by Bcl-2 family proteins.
AB  - Anti-cancer drugs that disrupt mitosis inhibit cell proliferation and induce
      apoptosis, although the mechanisms of these responses are poorly understood.
      Here, we characterize a mitotic stress response that determines cell fate in
      response to microtubule poisons. We show that mitotic arrest induced by these
      drugs produces a temporally controlled DNA damage response (DDR) characterized by
      the caspase-dependent formation of gammaH2AX foci in non-apoptotic cells.
      Following exit from a delayed mitosis, this initial response results in
      activation of DDR protein kinases, phosphorylation of the tumour suppressor p53
      and a delay in subsequent cell cycle progression. We show that this response is
      controlled by Mcl-1, a regulator of caspase activation that becomes degraded
      during mitotic arrest. Chemical inhibition of Mcl-1 and the related proteins Bcl
      2 and Bcl-xL by a BH3 mimetic enhances the mitotic DDR, promotes p53 activation
      and inhibits subsequent cell cycle progression. We also show that inhibitors of
      DDR protein kinases as well as BH3 mimetics promote apoptosis synergistically
      with taxol (paclitaxel) in a variety of cancer cell lines. Our work demonstrates
      the role of mitotic DNA damage responses in determining cell fate in response to
      microtubule poisons and BH3 mimetics, providing a rationale for anti-cancer
      combination chemotherapies. 

PMID- 25761372
TI  - Efficacy and tolerability of 16% subcutaneous immunoglobulin compared with 20%
      subcutaneous immunoglobulin in primary antibody deficiency.
AB  - Multiple subcutaneous immunoglobulin (SCIG) products are available to treat
      primary antibody deficiency (PAD). The efficacy and tolerability of 16% SCIG
      (Vivaglobin((r)) ) was compared with 20% SCIG (Hizentra((r)) ) in PAD subjects.
      The study was a prospective, single-centre, open-label study of PAD subjects
      transitioning Vivaglobin to equivalent Hizentra doses, rounded to the nearest
      vial size. Comparisons included immunoglobulin (Ig)G levels; tetanus, varicella
      and Streptococcus pneumoniae titres; adverse events (AEs), annual infection rate
      and quality of life during 8 weeks of Vivaglobin and 24 weeks of Hizentra. Thirty
      two subjects (aged 2-75 years) participated. Rounding to the nearest Hizentra
      vial size resulted in a 12.8% (+/- 2.9%) increase in SCIG dose. Median
      immunoglobulin (Ig)G level following 8 weeks of Vivaglobin was similar to 24
      weeks of Hizentra (1050 versus 1035 mg/dl, respectively; P = 0.77). Both products
      had similar protective titres to tetanus, varicella and serotypes of S.
      pneumoniae, which were variable but well above protective levels. After 12 weeks
      of Hizentra, subjects reported fewer local site reactions compared with
      Vivaglobin. Switching products resulted in increased systemic AEs in some
      subjects but, overall, not significantly higher than during Vivaglobin treatment.
      Average infusion time decreased from 104.7 min (3.3 sites) with Vivaglobin to
      70.7 min (2.2 sites) with Hizentra (P = 0.0005). Acute serious bacterial
      infections were similar. Treatment satisfaction was superior with Hizentra.
      Hizentra and Vivaglobin have similar pharmacokinetics and efficacy. Although
      transition to a different SCIG product initially increased AEs, Hizentra is well
      tolerated and can be infused more rapidly and with fewer sites compared to
      Vivaglobin. 

PMID- 25761373
TI  - Medicine-taking experiences and associated factors: comparison between Arabic
      speaking and Caucasian English-speaking patients with Type 2 diabetes.
AB  - AIM: The aim of this study was to explore and compare medication-taking
      experiences and associated issues in Arabic-speaking and Caucasian English
      speaking patients with Type 2 diabetes in Australia. METHODS: Various healthcare
      settings in metropolitan Melbourne, Australia, were purposefully selected to
      obtain a diverse group of participants with Type 2 diabetes. Recruitment occurred
      at diabetes outpatient clinics in two tertiary referral hospitals, six primary
      care practices and ten community centres. Face-to-face semi-structured individual
      interviews and group interviews were employed. All interviews were audiotaped,
      transcribed and coded thematically. Data collection continued until saturation
      was reached. RESULTS: In total, 100 participants were recruited into two groups:
      60 were Arabic-speaking and 40 were Caucasian English-speaking. Both groups had
      similar demographic and clinical characteristics. Only 5% of the Arabic-speaking
      participants had well-controlled diabetes compared with 17.5% of the participants
      in the English-speaking group. Arabic-speaking participants actively changed
      medication regimens on their own without informing their healthcare
      professionals. Arabic-speaking patients had more knowledge gaps about their
      prescribed treatments, compared with the English-speaking group. Their use of
      diabetes medicines was heavily influenced by peers with diabetes and family
      members; conversely, they feared revealing their diagnosis within the wider
      Arabic community due to stigma and collective negative social labelling of
      diabetes. Confidence in non-Arabic-speaking healthcare providers was lacking.
      CONCLUSIONS: Findings yielded new insights into medication-taking practices and
      associated factors in Arabic-speaking patients with diabetes. It is vital that
      healthcare professionals working with Arabic-speaking patients adapt their
      treatment approaches to accommodate different beliefs and views about medicines.

PMID- 25761374
TI  - Respiratory dysfunction in Charcot-Marie-Tooth disease type 1A.
AB  - We aimed to investigate the relationship between neurological compromise,
      respiratory parameters in wakefulness and in sleep, physiology, and morphology of
      phrenic nerves in patients with Charcot-Marie-Tooth disease type 1A (CMT1A).
      Sixteen patients with CMT1A were evaluated by spirometry, maximal expiratory and
      maximal inspiratory pressures (MEP, MIP), polysomnography, phrenic nerve compound
      muscle action potential (CMAP), and ultrasonography (roots C3,C4,C5 and phrenic
      nerves). Clinical disability was measured with Charcot-Marie-Tooth neuropathy
      score (CMT-NS; range 0-36). Two control groups, comprising 30 individuals matched
      for age, sex, and body mass index, were used for comparison. Ten patients were
      female (62%), mean age was 37.88 years (range 24-76); and CMT-NS range was 7-34.
      MIP was reduced in five (31%) and MEP in 12 patients (75%), although only one had
      restrictive respiratory dysfunction in spirometry. Apnoea-hypopnea index (AHI)
      was significantly higher in patients (12.01 +/- 11.57/h * 5.89 +/- 8.36/h; p
      value = 0.05) and increased in REM sleep compared with NREM (9.94 +/- 10.96/h *
      19.13 +/- 19.93/h; p value = 0.01). There were significant correlations between
      CMT-NS and AHI (Pearson = 0.69; p value = 0.03); CMT-NS and MIP (Pearson = 
      0.691, p value = 0.003); and CMT-NS and MEP (Pearson = -0.603, p value = 0.013).
      Also, AHI showed negative correlation with MIP (Pearson = -0.52, p value = 0.036)
      and MEP (Pearson = -0.55, p value = 0.026). Phrenic nerves were enlarged in
      ultrasonography in all patients and presented significant correlations with CMAPs
      (right: Pearson = -0.554, p value = 0.026; left: Pearson = -0.558, p value =
      0.025). We suggest that axonal degeneration of nerves directed to muscles of
      respiration might explain the high prevalence of respiratory weakness in patients
      with CMT1A. Clinical manifestations are frequent during sleep, where the
      diaphragm alone can only partially surpass the overload in breathing apparatus.

PMID- 25761375
TI  - On visual hallucinations and cortical networks: a trans-diagnostic review.
AB  - Our current clinical approach to visual hallucinations is largely derived from
      work carried out by Georges de Morsier in the 1930s. Now, almost a century after
      his influential papers, we have the research tools to further explore the ideas
      he put forward. In this review, we address de Morsier's proposal that visual
      hallucinations in all clinical conditions have a similar neurological mechanism
      by comparing structural imaging studies of susceptibility to visual
      hallucinations in Parkinson's disease, Alzheimer's disease, Dementia with Lewy
      bodies and schizophrenia. Systematic review of the literature was undertaken
      using PubMed searches. A total of 18 studies across conditions were identified
      reporting grey matter differences between patients with and without visual
      hallucinations. Grey matter changes were categorised into brain regions relevant
      to current theories of visual hallucinations. The distribution of cortical
      atrophy supports de Morsier's premise that visual hallucinations are invariably
      linked to aberrant activity within visual thalamo-cortical networks. Further work
      is required to determine by what mechanism these networks become predisposed to
      spontaneous activation, and whether the frontal lobe and hippocampal changes
      identified are present in all conditions. The findings have implications for the
      development of effective treatments for visual hallucinations. 

PMID- 25761376
TI  - Can MS lesion stages be distinguished with MRI? A postmortem MRI and
      histopathology study.
AB  - In multiple sclerosis (MS), a histopathological distinction is made between
      different stages of white matter (WM) lesions. These lesions are characterized as
      preactive, active, chronic active or chronic inactive, depending on the degree of
      microglia activation and degree of demyelination. The different lesions are not
      distinguishable on conventional magnetic resonance imaging (MRI) scans at
      standard clinical field strengths, but might be distinguished using more
      advanced, quantitative MRI methods, such as T1 relaxation time (T1-RT) mapping.
      To investigate this, postmortem brain material from 20 MS patients was
      investigated, using both T1-RT MRI at 1.5 T and histopathology. The brain
      material contained a total of 9 preactive, 18 active, 30 chronic active and 14
      chronic inactive lesions, as well as 38 areas of normal appearing WM (NAWM). Our
      results show that, at 1.5 T, T1-RT qMRI can only distinguish between categories
      NAWM/preactive, active and chronic WM lesions. Advanced imaging at standard field
      strengths, such as conventional imaging measures, is therefore insufficient to
      differentiate the WM lesions in MS, and higher field strengths may be required to
      achieve better pathological differentiation of these lesions.

PMID- 25761377
TI  - Acute disseminated encephalomyelitis: current controversies in diagnosis and
      outcome.
AB  - Acute disseminated encephalomyelitis (ADEM) is a rare inflammatory, demyelinating
      disorder of the CNS. Only in the past 15 years have larger groups of patients
      from several geographical areas been reported for comparisons across studies. In
      spite of the increased recognition of ADEM, the diagnosis of ADEM remains
      clinical, aided by neuroimaging confirmation, because of the lack of a biological
      marker. The diagnosis may be difficult, given that several diseases may present
      similar to ADEM. The controversial existence of multiphasic forms necessitates a
      continuous evaluation of the diagnosis by tracking subsequent events. Despite
      proposed consensus criteria, the diagnostic criteria employed to characterize
      ADEM range widely among the largest reported cohorts to date. This review
      comprehensively evaluates the current knowledge and controversies that surround
      ADEM, with special consideration of the distinction between ADEM and other
      demyelinating diseases such as multiple sclerosis. In addition, we present
      implications of the current knowledge of ADEM for both research and clinical
      practice. 

PMID- 25761378
TI  - Jan Piltz (1870-1930).

PMID- 25761379
TI  - Guidelines, polypharmacy, and drug-drug interactions in patients with
      multimorbidity.

PMID- 25761381
TI  - Strong magnetic field-assisted growth of carbon nanofibers and its
      microstructural transformation mechanism.
AB  - It is well-known that electric and magnetic fields can control the growth
      direction, morphology and microstructure of one-dimensional carbon nanomaterials
      (1-DCNMs), which plays a key role for its potential applications in micro-nano
      electrics and devices. In this paper, we introduce a novel process for
      controlling growth of carbon nanofibers (CNFs) with assistance of a strong
      magnetic field (up to 0.5 T in the center) in a chemical vapor deposition (CVD)
      system. The results reveal that: 1) The CNFs get bundled when grown in the
      presence of a strong magnetic field and slightly get aligned parallel to the
      direction of the magnetic field; 2) The CNFs diameter become narrowed and
      homogenized with increase of the magnetic field; 3) With the increase of the
      magnetic field, the microstructure of CNFs is gradually changed, i.e., the strong
      magnetic field makes the disordered "solid-cored" CNFs transform into a kind of
      bamboo-liked carbon nanotubes; 4) We propose a mechanism that the reason for
      these variations and transformation is due to diamagnetic property of carbon
      atoms, so that it has direction selectivity in the precipitation process. 

PMID- 25761380
TI  - Health surveillance under adverse ergonomics conditions--validity of a screening
      method adapted for the occupational health service.
AB  - A new health surveillance protocol for work-related upper-extremity
      musculoskeletal disorders has been validated by comparing the results with a
      reference protocol. The studied protocol, Health Surveillance in Adverse
      Ergonomics Conditions (HECO), is a new version of the reference protocol modified
      for application in the Occupational Health Service (OHS). The HECO protocol
      contains both a screening part and a diagnosing part. Sixty-three employees were
      examined. The screening in HECO did not miss any diagnosis found when using the
      reference protocol, but in comparison to the reference protocol considerable time
      savings could be achieved. Fair to good agreement between the protocols was
      obtained for one or more diagnoses in neck/shoulders (86%, k = 0.62) and
      elbow/hands (84%, k = 0.49). Therefore, the results obtained using the HECO
      protocol can be compared with a reference material collected with the reference
      protocol, and thus provide information of the magnitude of disorders in an
      examined work group. Practitioner Summary: The HECO protocol is a relatively
      simple physical examination protocol for identification of musculoskeletal
      disorders in the neck and upper extremities. The protocol is a reliable and cost
      effective tool for the OHS to use for occupational health surveillance in order
      to detect workplaces at high risk for developing musculoskeletal disorders. 

PMID- 25761382
TI  - Abstracts of the Fifth Biennial Congress of the Asian-Pacific Hepato-Pancreato
      Biliary Association, 18-21 March, 2015, Singapore.

PMID- 25761383
TI  - Uphill diffusion in multicomponent mixtures.
AB  - Molecular diffusion is an omnipresent phenomena that is important in a wide
      variety of contexts in chemical, physical, and biological processes. In the
      majority of cases, the diffusion process can be adequately described by Fick's
      law that postulates a linear relationship between the flux of any species and its
      own concentration gradient. Most commonly, a component diffuses down the
      concentration gradient. The major objective of this review is to highlight a very
      wide variety of situations that cause the uphill transport of one constituent in
      the mixture. Uphill diffusion may occur in multicomponent mixtures in which the
      diffusion flux of any species is strongly coupled to that of its partner species.
      Such coupling effects often arise from strong thermodynamic non-idealities. For a
      quantitative description we need to use chemical potential gradients as driving
      forces. The transport of ionic species in aqueous solutions is coupled with its
      partner ions because of the electro-neutrality constraints; such constraints may
      accelerate or decelerate a specific ion. When uphill diffusion occurs, we observe
      transient overshoots during equilibration; the equilibration process follows
      serpentine trajectories in composition space. For mixtures of liquids, alloys,
      ceramics and glasses the serpentine trajectories could cause entry into meta
      stable composition zones; such entry could result in phenomena such as spinodal
      decomposition, spontaneous emulsification, and the Ouzo effect. For distillation
      of multicomponent mixtures that form azeotropes, uphill diffusion may allow
      crossing of distillation boundaries that are normally forbidden. For mixture
      separations with microporous adsorbents, uphill diffusion can cause supra
      equilibrium loadings to be achieved during transient uptake within crystals; this
      allows the possibility of over-riding adsorption equilibrium for achieving
      difficult separations. 

PMID- 25761385
TI  - Active link selection for efficient semi-supervised community detection.
AB  - Several semi-supervised community detection algorithms have been proposed
      recently to improve the performance of traditional topology-based methods.
      However, most of them focus on how to integrate supervised information with
      topology information; few of them pay attention to which information is critical
      for performance improvement. This leads to large amounts of demand for supervised
      information, which is expensive or difficult to obtain in most fields. For this
      problem we propose an active link selection framework, that is we actively select
      the most uncertain and informative links for human labeling for the efficient
      utilization of the supervised information. We also disconnect the most likely
      inter-community edges to further improve the efficiency. Our main idea is that,
      by connecting uncertain nodes to their community hubs and disconnecting the inter
      community edges, one can sharpen the block structure of adjacency matrix more
      efficiently than randomly labeling links as the existing methods did. Experiments
      on both synthetic and real networks demonstrate that our new approach
      significantly outperforms the existing methods in terms of the efficiency of
      using supervised information. It needs ~13% of the supervised information to
      achieve a performance similar to that of the original semi-supervised approaches.

PMID- 25761386
TI  - Synthesis of Mono-PEGylated Growth Hormone Releasing Peptide-2 and Investigation
      of its Biological Activity.
AB  - The purpose of this study was to investigate an efficient synthetic route to the
      mono-PEGylated growth hormone releasing peptide-2 (GHRP-2) and its biological
      activity in vivo. The commercially available key PEGylating reagent, mPEG-NHS
      ester, was successfully utilized to the synthesis of mono-PEGylated GHRP-2,
      during which the PEGylation profiles of GHRP-2 were monitored by high-performance
      liquid chromatography (HPLC). The product was purified by cation exchange
      chromatography, and its biological activity was conducted in rats. The desired
      mono-PEGylated GHRP-2 as the major product was readily obtained in anhydrous
      aprotic solvent, such as dimethyl formamide (DMF) and dimethylsulfoxide (DMSO),
      when the molar ratio of mPEG-NHS ester to GHRP-2 was fixed to be 0.8:1. The
      products were characterized by matrix-assisted laser desorption ionization time
      of-flight (MALDI-TOF) mass spectrometry. The evaluation of the biological
      activity for the products showed that the mono-PEGylated GHRP-2 gave a more
      stable activity than GHRP-2, suggesting that PEGylation led to the increase in
      the half-life of GHRP-2 in plasma without greatly impairing the biological
      activity. PEGylation of the GHRP-2 is a good choice for the development of the
      GHRP-2 applications.

PMID- 25761387
TI  - Drying Using Supercritical Fluid Technology as a Potential Method for Preparation
      of Chitosan Aerogel Microparticles.
AB  - Supercritical fluid technology offers several advantages in preparation of
      microparticles. These include uniformity in particle size, morphology, and drug
      distribution without degradation of the product. One of the recent advantages is
      preparation of porous aerogel carrier with proper aerodynamic properties. In this
      study, we aimed to prepare chitosan aerogel microparticles using supercritical
      fluid (SCF) technology and compare that with microparticles produced by freeze
      drying (FD). Loading the prepared carriers with a model drug (salbutamol) was
      also performed. Comparisons of the particle properties and physicochemical
      characterizations were undertaken by evaluating particle size, density, specific
      surface area, and porosity. In vitro drug release studies were also investigated.
      The effect of many variables, such as molecular weight of chitosan oligomers,
      concentrations of chitosan, and concentrations of tripolyphosphate on the
      release, were also investigated. Chitosan aerogels were efficiently produced by
      SCF technology with an average particle size of 10 MUm with a tapped density
      values around 0.12 g/mL, specific surface area (73-103) m(2)/g, and porosity
      (0.20-0.29) cc/g. Whereas, microparticles produced by FD method were
      characterized as cryogels with larger particle size (64 microns) with clear
      cracking at the surface. Sustained release profile was achieved for all prepared
      microparticles of salbutamol produced by the aforementioned methods as compared
      with pure drug. The results also demonstrates that chitosan molecular weight,
      polymer concentration, and tripolyphosphate concentration affected the release
      profile of salbutamol from the prepared microparticles. In conclusion, SCF
      technology was able to produce chitosan aerogel microparticles loaded with
      salbutamol that could be suitable for pulmonary drug delivery system.

PMID- 25761388
TI  - A mesoporous metal-organic framework based on a shape-persistent macrocycle.
AB  - A mesoporous Zn-based metal-organic framework (MOF) was prepared from a shape
      persistent phenylene ethynylene macrocycle functionalized with three -COOH
      groups. The rigid ligand has a ~9 A wide central cavity which serves as a
      predesigned pore. The macrocycles [pi...pi] stack into pairs, with their
      carboxylate groups connected via three Zn3O14C6H2 clusters. The resulting MOF has
      a void volume of 86%.

PMID- 25761389
TI  - Meta-T: TetrisR as an experimental paradigm for cognitive skills research.
AB  - Studies of human performance in complex tasks using video games are an attractive
      prospect, but many existing games lack a comprehensive way to modify the game and
      track performance beyond basic levels of analysis. Meta-T provides experimenters
      a tool to study behavior in a dynamic task environment with time-stressed
      decision-making and strong perceptual-motor elements, offering a host of
      experimental manipulations with a robust and detailed logging system for all user
      events, system events, and screen objects. Its experimenter-friendly interface
      provides control over detailed parameters of the task environment without need
      for programming expertise. Support for eye-tracking and computational cognitive
      modeling extend the paradigm's scope. 

PMID- 25761390
TI  - Psychophysics in a Web browser? Comparing response times collected with
      JavaScript and Psychophysics Toolbox in a visual search task.
AB  - Behavioral researchers are increasingly using Web-based software such as
      JavaScript to conduct response time experiments. Although there has been some
      research on the accuracy and reliability of response time measurements collected
      using JavaScript, it remains unclear how well this method performs relative to
      standard laboratory software in psychologically relevant experimental
      manipulations. Here we present results from a visual search experiment in which
      we measured response time distributions with both Psychophysics Toolbox (PTB) and
      JavaScript. We developed a methodology that allowed us to simultaneously run the
      visual search experiment with both systems, interleaving trials between two
      independent computers, thus minimizing the effects of factors other than the
      experimental software. The response times measured by JavaScript were
      approximately 25 ms longer than those measured by PTB. However, we found no
      reliable difference in the variability of the distributions related to the
      software, and both software packages were equally sensitive to changes in the
      response times as a result of the experimental manipulations. We concluded that
      JavaScript is a suitable tool for measuring response times in behavioral
      research. 

PMID- 25761391
TI  - Efficient simulation of diffusion-based choice RT models on CPU and GPU.
AB  - In this paper, we present software for the efficient simulation of a broad class
      of linear and nonlinear diffusion models for choice RT, using either CPU or
      graphical processing unit (GPU) technology. The software is readily accessible
      from the popular scripting languages MATLAB and R (both 64-bit). The speed
      obtained on a single high-end GPU is comparable to that of a small CPU cluster,
      bringing standard statistical inference of complex diffusion models to the
      desktop platform. 

PMID- 25761393
TI  - Algorithmic complexity for psychology: a user-friendly implementation of the
      coding theorem method.
AB  - Kolmogorov-Chaitin complexity has long been believed to be impossible to
      approximate when it comes to short sequences (e.g. of length 5-50). However, with
      the newly developed coding theorem method the complexity of strings of length 2
      11 can now be numerically estimated. We present the theoretical basis of
      algorithmic complexity for short strings (ACSS) and describe an R-package
      providing functions based on ACSS that will cover psychologists' needs and
      improve upon previous methods in three ways: (1) ACSS is now available not only
      for binary strings, but for strings based on up to 9 different symbols, (2) ACSS
      no longer requires time-consuming computing, and (3) a new approach based on ACSS
      gives access to an estimation of the complexity of strings of any length.
      Finally, three illustrative examples show how these tools can be applied to
      psychology. 

PMID- 25761392
TI  - The Oriented Difference of Gaussians (ODOG) model of brightness perception:
      Overview and executable Mathematica notebooks.
AB  - The Oriented Difference of Gaussians (ODOG) model of brightness (perceived
      intensity) by Blakeslee and McCourt (Vision Research 39:4361-4377, 1999), which
      is based on linear spatial filtering by oriented receptive fields followed by
      contrast normalization, has proven highly successful in parsimoniously predicting
      the perceived intensity (brightness) of regions in complex visual stimuli such as
      White's effect, which had been believed to defy filter-based explanations. Unlike
      competing explanations such as anchoring theory, filling-in, edge-integration, or
      layer decomposition, the spatial filtering approach embodied by the ODOG model
      readily accounts for the often overlooked but ubiquitous gradient structure of
      induction which, while most striking in grating induction, also occurs within the
      test fields of classical simultaneous brightness contrast and the White stimulus.
      Also, because the ODOG model does not require defined regions of interest, it is
      generalizable to any stimulus, including natural images. The ODOG model has
      motivated other researchers to develop modified versions (LODOG and FLODOG), and
      has served as an important counterweight and proof of concept to constrain high
      level theories which rely on less well understood or justified mechanisms such as
      unconscious inference, transparency, perceptual grouping, and layer
      decomposition. Here we provide a brief but comprehensive description of the ODOG
      model as it has been implemented since 1999, as well as working Mathematica
      (Wolfram, Inc.) notebooks which users can employ to generate ODOG model
      predictions for their own stimuli. 

PMID- 25761394
TI  - A reminder on millisecond timing accuracy and potential replication failure in
      computer-based psychology experiments: An open letter.
AB  - There is an ongoing 'replication crisis' across the field of psychology in which
      researchers, funders, and members of the public are questioning the results of
      some scientific studies and the validity of the data they are based upon.
      However, few have considered that a growing proportion of research in modern
      psychology is conducted using a computer. Could it simply be that the hardware
      and software, or experiment generator, being used to run the experiment itself be
      a cause of millisecond timing error and subsequent replication failure? This
      article serves as a reminder that millisecond timing accuracy in psychology
      studies remains an important issue and that care needs to be taken to ensure that
      studies can be replicated on current computer hardware and software. 

PMID- 25761395
TI  - Attentive Turkers: MTurk participants perform better on online attention checks
      than do subject pool participants.
AB  - Participant attentiveness is a concern for many researchers using Amazon's
      Mechanical Turk (MTurk). Although studies comparing the attentiveness of
      participants on MTurk versus traditional subject pool samples have provided mixed
      support for this concern, attention check questions and other methods of ensuring
      participant attention have become prolific in MTurk studies. Because MTurk is a
      population that learns, we hypothesized that MTurkers would be more attentive to
      instructions than are traditional subject pool samples. In three online studies,
      participants from MTurk and collegiate populations participated in a task that
      included a measure of attentiveness to instructions (an instructional
      manipulation check: IMC). In all studies, MTurkers were more attentive to the
      instructions than were college students, even on novel IMCs (Studies 2 and 3),
      and MTurkers showed larger effects in response to a minute text manipulation.
      These results have implications for the sustainable use of MTurk samples for
      social science research and for the conclusions drawn from research with MTurk
      and college subject pool samples. 

PMID- 25761396
TI  - Effects of 2-amino-8-hydroxyquinoline interaction on the conformation of
      physiological isomers of human serum albumin.
AB  - The methods of synthetic chemistry create small molecules rapidly for screening,
      and ligand-protein interaction studies provide information on how a potential
      drug interacts with target or carrier proteins such as serum albumin. In this
      work, we investigate the interaction of amino derivative of 8-hydroxyquinoline, 2
      amino-8-hydroxyquinoline (A8HQ), and the effects of its binding on the
      conformation of different isomers of human serum albumin (HSA) using
      multispectroscopic techniques and molecular modeling. We found that B isomer,
      which exists at pH 9, bound A8HQ (K a = 1.92 +/- 0.07 * 10(5) M(-1) at 298 K)
      more strongly as compared with N isomer (K a = 1.19 +/- 0.04 * 10(5) M(-1) at 298
      K) of HSA, which is known to exist around pH 6. The binding constant at
      physiological pH (7.4) was also determined, and the value (K a = 1.38 +/- 0.05 *
      10(5) M(-1) at 298 K) was found to fall between those for N and B isomers,
      suggesting that both the N and B isomers exist in an equilibrium in plasma. We
      also determined the thermodynamic parameters such as changes in enthalpy, entropy
      , and free energy of binding by measuring the binding at four different
      temperatures. Based on molecular modeling and thermodynamic studies, we propound
      that the A8HQ-HSA binding involves mainly hydrophobic interactions and hydrogen
      bonding. Site-specific marker displacement experiments and molecular modeling
      showed that the molecule preferably binds in subdomain IIA close to Trp214. A8HQ
      binding to HSA isomers was found to cause both secondary and tertiary structural
      alterations in the protein.

PMID- 25761397
TI  - Therapeutic role of curcumin in oxidative DNA damage caused by formaldehyde.
AB  - PURPOSE: Formaldehyde is a common environmental contaminant that causes oxidative
      DNA damage in cells by increasing the production of reactive oxygen species. The
      aim of this study was to investigate the amount of 8-hydroxy-deoxyguanosine (8
      OhdG), tumor protein 53(TP53), beta-amyloid[Abeta(1-42), Abeta (1-40)], total
      antioxidant capacity (TAC) and malondialdehyde (MDA) and the therapeutic role of
      curcumin in rat cells with oxidative DNA damage caused by formaldehyde. METHOD:
      The control group was given physiological saline for 15 days (i.p.) and the
      second group was given 37% formaldehyde (i.p.) at a dose of 9 mg/kg group every
      other day. The third group was given 9 mg/kg formaldehyde (i.p.) every other day
      and treated therapeutically with 100 mg/kg curcumin every day by gavage. At the
      end of the trial period, urine, blood, and brain tissue was collected from the
      rats. RESULTS: The levels of MDA in sera were increased and the TAC, TP53, and
      Abeta (1-40) levels were reduced in the formaldehyde-treated group with respect
      to the control group (p<0.005). After treatment with curcumin, the levels of sera
      MDA were significantly reduced, the TAC, TP53, and Abeta (1-40) levels were
      significantly increased (P < 0.05). The levels of whole brain Abeta (1-42) and 8
      OhdG were increased in the formaldehyde-treated group and reduced after treatment
      with curcumin (P < 0.05). Urinary 8-OhdG excretion increased in the formaldehyde
      treated group (P < 0.05) and decreased after treatment with curcumin (P > 0.05).
      CONCLUSIONS: In conclusion, the oxidative stress caused by formaldehyde exposure
      was reduced with the application of curcumin.

PMID- 25761398
TI  - Waste Separation Press (WSP): a mechanical pretreatment option for organic waste
      from source separation.
AB  - An efficient biological treatment of source separated organic waste from
      household kitchens and gardens (biowaste) requires an adequate upfront mechanical
      preparation which possibly includes a hand sorting for the separation of
      contaminants. In this work untreated biowaste from households and gardens and the
      screen overflow >60mm of the same waste were mechanically treated by a Waste
      Separation Press (WSP). The WSP separates the waste into a wet fraction for
      biological treatment and a fraction of dry contaminants for incineration. The
      results show that it is possible to replace a hand sorting of contaminants, the
      milling and a screening of organic waste before the biological treatment by using
      the WSP. A special focus was put on the contaminants separation. The separation
      of plastic film from the untreated biowaste was 67% and the separation rate of
      glass was about 92%. About 90% of the organics were transferred to the fraction
      for further biological treatment. When treating the screen overflow >60mm with
      the WSP 86% of the plastic film and 88% of the glass were transferred to the
      contaminants fraction. 32% of the organic was transferred to the contaminants
      fraction and thereby lost for a further biological treatment. Additionally it was
      calculated that national standards for glass contaminants in compost can be met
      when using the WSP to mechanically treat the total biowaste. The loss of biogas
      by transferring biodegradable organics to the contaminants fraction was about 11%
      when preparing the untreated biowaste with the WSP. 

PMID- 25761399
TI  - Vibrationally Resolved B 1s Photoionization Cross Section of BF3.
AB  - Photoelectron diffraction is a well-established technique for structural
      characterization of solids, based on the interference of the native photoelectron
      wave with those scattered from the neighboring atoms. For isolated systems in the
      gas phase similar studies suffer from orders of magnitude lower signals due to
      the very small sample density. Here we present a detailed study of the
      vibrationally resolved B 1s photoionization cross section of BF3 molecule. A
      combination of high-resolution photoelectron spectroscopy measurements and of
      state-of-the-art static-exchange and time-dependent DFT calculations shows the
      evolution of the photon energy dependence of the cross section from a complete
      trapping of the photoelectron wave (low energies) to oscillations due to
      photoelectron diffraction phenomena. The diffraction pattern allows one to access
      structural information both for the ground neutral state of the molecule and for
      the core-ionized cation. Due to a significant change in geometry between the
      ground and the B 1s(-1) core-ionized state in the BF3 molecule, several
      vibrational final states of the cation are populated, allowing investigation of
      eight different relative vibrationally resolved photoionization cross sections.
      Effects due to recoil induced by the photoelectron emission are also discussed. 

PMID- 25761400
TI  - [Sarcoma of the hand and wrist].
AB  - Sarcomas of the hand and wrist are rare malignancies, which should be referred to
      high-volume comprehensive cancer centres providing multidisciplinary treatment
      options. The tumour board should propose patient-oriented oncological pathways as
      well as sophisticated hand and plastic reconstructive procedures. In Addition,
      isolated limb perfusion with TNF-alpha and melphalan is likely to lead to
      preoperative tumour shrinkage allowing for R0 resection in sano. Our clinical
      results in long-term survivors demonstrate reduced amputation rates and salvage
      of basic hand function when a risk-adapted treatment rationale is applied. 

PMID- 25761401
TI  - Do water quality criteria based on nonnative species provide appropriate
      protection for native species?
AB  - The potential use of toxicity data for nonnative species to derive water quality
      criteria is controversial because it is sometimes questioned whether criteria
      based on species from one geographical region provide appropriate protection for
      species in a different region. However, this is an important concept for the
      development of Chinese water quality criteria or standards. Data were assembled
      on 38 chemicals for which values were available for both native and nonnative
      species. Sensitivities of these organisms were compared based on the 5% hazardous
      concentration values and the species sensitivity distribution from a literature
      review. Results of the present study's analysis showed that there is
      approximately 74% certainty that use of nonnative species to generate water
      quality criteria would be sufficiently protective of aquatic ecosystems in China.
      Without applying any assessment factor to the water quality criteria generated
      from nonnative species, the uncertainty would be 26% when the native Chinese
      species might be under protection. Applying an assessment factor of 10 would
      offer adequate protection to native Chinese species for approximately 90% of
      tested chemicals and thus reduce the uncertainty from 26% to 10%.

PMID- 25761402
TI  - Information of prostate biopsy positive core: does it affect MR detection of
      prostate cancer on using 3T-MRI?
AB  - OBJECTIVE: We assessed which information from a prostate biopsy had the strongest
      relationship with prostate cancer detection by 3T-MRI. MATERIALS AND METHODS:
      Sixty-one consecutive patients with biopsy-proven prostate cancer who underwent
      3T-MRI before biopsy were enrolled in this retrospective study. Two radiologists
      independently reviewed T2-weighted and diffusion-weighted images. When the cancer
      lesions were revealed by biopsy and MRI depicted them at corresponding sites, we
      classified these lesions as MRI-detectable cancer. If the cancer lesions were
      revealed by biopsy, but any cancers had not been detected, we classified these
      lesions as MRI-undetectable cancer. We compared the Gleason score (GS), cancer
      ratio (CaR) and cancer length (CaL) from core biopsies between the two groups.
      THE RESULTS: GS, CaR and CaL differed significantly between the MRI-detectable
      group (N = 70), and the MRI-undetectable group (N = 73). 3T-MRI could detect
      cancer cores with a sensitivity of 90.5% in cores with CaR >= 60%, and with a
      sensitivity of 81.8% in those with CaL >= 5 mm. Receiver operating characteristic
      analysis showed that CaR (P = 0.006) and CaL (P = 0.010) significantly associated
      with the prostate cancer detection using MRI rather than GS. CONCLUSION: CaR and
      CaL from the core biopsies showed a stronger relationship to detection of the
      prostate cancer on 3T-MRI than the GS did.

PMID- 25761403
TI  - Serological comparison of antibodies to avian influenza viruses, subtypes H5N2,
      H6N1, H7N3 and H7N9 between poultry workers and non-poultry workers in Taiwan in
      2012.
AB  - In Taiwan, avian influenza virus (AIV) subtypes H5N2, H6N1 and H7N3 have been
      identified in domestic poultry, and several strains of these subtypes have become
      endemic in poultry. To evaluate the potential of avian-to-human transmission due
      to occupational exposure, an exploratory analysis of AIV antibody status in
      poultry workers was conducted. We enrolled 670 poultry workers, including 335
      live poultry vendors (LPVs), 335 poultry farmers (PFs), and 577 non-poultry
      workers (NPWs). Serum antibody titres against various subtypes of viruses were
      analysed and compared. The overall seropositivity rates in LPVs and PFs were
      2.99% (10/335) and 1.79% (6/335), respectively, against H5N2; and 0.6% (2/335)
      and 1.19% (4/335), respectively, for H7N3 virus. Of NPWs, 0.35% (2/577) and 0.17%
      (1/577) were seropositive for H5N2 and H7N3, respectively. Geographical analysis
      revealed that poultry workers whose workplaces were near locations where H5N2
      outbreaks in poultry have been reported face greater risks of being exposed to
      viruses that result in elevated H5N2 antibody titres. H6N1 antibodies were
      detected in only one PF, and no H7N9 antibodies were found in the study subjects.
      Subclinical infections caused by H5N2, H6N1 and H7N3 viruses were thus identified
      in poultry workers in Taiwan. Occupational exposure is associated with a high
      risk of AIV infection, and the seroprevalence of particular avian influenza
      strains in humans reflects the endemic strains in poultry in this region. 

PMID- 25761404
TI  - Improved hole-transporting property via HAT-CN for perovskite solar cells without
      lithium salts.
AB  - A nonadditive hole-transporting material (HTM) of a triphenylamine derivative of
      N,N'-di(3-methylphenyl)-N,N'-diphenyl-4,4'-diaminobiphenyl (TPD) is used for the
      organic-inorganic hybrid perovskite solar cells. The power conversion efficiency
      (PCE) can be significantly enhanced by inserting a thin layer of 1,4,5,8,9,11
      hexaazatriphenylenehexacarbonitrile (HAT-CN) without adding an ion additive
      because the hole-transporting properties improve. The short-circuit current
      density (J(sc)) increases from 8.5 to 13.1 mA/cm(2), the open-circuit voltage
      (V(oc)) increases from 0.84 to 0.92 V, and the fill-factor (FF) increases from
      0.45 to 0.59, which corresponds to the increase in PCE from 3.2% to 7.1%.
      Moreover, the PCE decreases by only 10% after approximately 1000 h without
      encapsulation, which suggests an alternative method to improve the stability of
      perovskite solar cells.

PMID- 25761405
TI  - Intrauterine Growth Restricted Rats Exercised at Pregnancy: Maternal-Fetal
      Repercussions.
AB  - To evaluate the effect of swimming in pregnant rats born with intrauterine growth
      restriction (IUGR) and their offspring, IUGR rats were obtained using the
      streptozotocin-induced severe diabetic (SD) rats. In this study, the nondiabetic
      parental generation presented 10 rats and diabetic parental generation presented
      116 rats. Of these, the mated nondiabetic female rats were 10 and the number of
      diabetic rats was 45. In relation to term pregnancy, there were 10 animals in the
      nondiabetic group and 15 rats in the diabetic group. In the offspring of SD rats
      (IUGR group), 43 females were classified as small for pregnancy age, 19 rats were
      classified as appropriate for pregnancy age, and 0 female was classified as large
      for pregnancy age. The nondiabetic and SD pregnant rats generated offspring with
      appropriate (control [C]) and small (IUGR) weight for pregnancy age,
      respectively. At adult life, the C group was maintained as nonexercised C group
      and IUGR rats were distributed into 2 subgroups, namely, nonexercised (IUGR) and
      exercised (IUGRex). The rate of mated rats in the IUGR group was reduced compared
      to the C group. During pregnancy, the IUGR rats presented hyperinsulinemia,
      impaired reproductive outcomes, decreased body weight, hypertriglyceridemia, and
      hyperlactacidemia. The IUGRex presented reduced insulin and triglyceride levels.
      Thus, swimming improved lipid metabolism and increased insulin sensitivity.
      However, the offspring showed retarded growth, reinforcing the need to stimulate
      the exercise practice in women under supervision with different professional
      expertise to promote appropriate gestational conditions and improve perinatal
      outcomes. 

PMID- 25761406
TI  - A comparative analysis of breast cancer stage between women enrolled in the
      National Breast and Cervical Cancer Early Detection Program and women not
      participating in the program.
AB  - PURPOSE: To determine the proportional distribution of early- and late-stage
      breast cancers diagnosed in years 2004-2009 among women enrolled in the National
      Breast and Cervical Cancer Early Detection Program (NBCCEDP) and to compare this
      distribution to that of geographically comparable non-enrolled women diagnosed
      with breast cancer. METHODS: Using data from the National Program of Cancer
      Registries, we compared the demographic characteristics and cancer stage
      distribution of women enrollees and non-enrollees by use of conditional logistic
      regression using the odds ratio as a measure of association. RESULTS: NBCCEDP
      enrollees were slightly younger and more likely to identify as African-American,
      API and AIAN than were non-enrollees. The proportion of late-stage breast cancer
      (regional and distant) decreased slightly over the study period. NBCCEDP
      enrollees generally were diagnosed at a later stage of breast cancer than were
      those not enrolled in the NBCCEDP. CONCLUSIONS: The NBCCEDP has been effective in
      achieving its goal of enrolling racial and ethnic populations; however, enrollees
      had a poorer stage distribution of breast cancer than did non-enrollees
      underscoring the need to expand breast cancer control efforts among low-income,
      underserved populations.

PMID- 25761407
TI  - Association of genetic variation in IKZF1, ARID5B, and CEBPE and surrogates for
      early-life infections with the risk of acute lymphoblastic leukemia in Hispanic
      children.
AB  - BACKGROUND: Genome-wide association studies focusing on European-ancestry
      populations have identified ALL risk loci on IKZF1, ARID5B, and CEBPE. To capture
      the impacts of these genes on ALL risk in the California Hispanic population, we
      comprehensively assessed the variation within the genes and further assessed the
      joint effects between the genetic variation and surrogates for early-life
      infections (the presence of older siblings, daycare attendance, and ear
      infections). METHODS: Genotypic data for 323 Hispanic ALL cases and 454 controls
      from the California Childhood Leukemia Study were generated using Illumina
      OmniExpress v1 platform. Logistic regression assuming a log-additive model
      estimated odds ratios (OR) associated with each SNP, adjusted for age, sex, and
      the first five principal components. In addition, we examined potential
      interactions between six ALL risk alleles and surrogates for early-life
      infections using logistic regression models that included an interaction term.
      RESULTS: Significant associations between genotypes at IKZF1, ARID5B, and CEBPE
      and ALL risk were identified: rs7780012, OR 0.50, 95% confidence interval (CI)
      0.35-0.71 (p = 0.004); rs7089424, OR 2.12, 95% CI 1.70-2.65 (p = 1.16 * 10(-9));
      rs4982731, OR 1.69, 95% CI 1.37-2.08 (p = 2.35 * 10(-6)), respectively. Evidence
      for multiplicative interactions between genetic variants and surrogates for early
      life infections with ALL risk was not observed. CONCLUSIONS: Consistent with
      findings in non-Hispanic White population, our study showed that variants within
      IKZF1, ARID5B, and CEBPE were associated with increased ALL risk, and the effects
      for ARID5B and CEBPE were most prominent in the high-hyperdiploid ALL subtype in
      the California Hispanic population. Results implicate the ARID5B, CEBPE, and
      IKZF1 genes in the pathogenesis of childhood ALL.

PMID- 25761408
TI  - Mammographic density and breast cancer risk by family history in women of white
      and Asian ancestry.
AB  - PURPOSE: Mammographic density, i.e., the radiographic appearance of the breast,
      is a strong predictor of breast cancer risk. To determine whether the association
      of breast density with breast cancer is modified by a first-degree family history
      of breast cancer (FHBC) in women of white and Asian ancestry, we analyzed data
      from four case-control studies conducted in the USA and Japan. METHODS: The study
      population included 1,699 breast cancer cases and 2,422 controls, of whom 45%
      reported white (N = 1,849) and 40% Asian (N = 1,633) ancestry. To standardize
      mammographic density assessment, a single observer re-read all mammograms using
      one type of interactive thresholding software. Logistic regression was applied to
      estimate odds ratios (OR) while adjusting for confounders. RESULTS: Overall, 496
      (12%) of participants reported a FHBC, which was significantly associated with
      breast cancer risk in the adjusted model (OR 1.51; 95% CI 1.23-1.84). There was a
      statistically significant interaction on a multiplicative scale between FHBC and
      continuous percent density (per 10 % density: p = 0.03). The OR per 10% increase
      in percent density was higher among women with a FHBC (OR 1.30; 95% CI 1.13-1.49)
      than among those without a FHBC (OR 1.14; 1.09-1.20). This pattern was apparent
      in whites and Asians. The respective ORs were 1.45 (95% CI 1.17-1.80) versus 1.22
      (95% CI 1.14-1.32) in whites, whereas the values in Asians were only 1.24 (95% CI
      0.97-1.58) versus 1.09 (95% CI 1.00-1.19). CONCLUSIONS: These findings support
      the hypothesis that women with a FHBC appear to have a higher risk of breast
      cancer associated with percent mammographic density than women without a FHBC.

PMID- 25761409
TI  - Dietary patterns and endometrial cancer risk in the California Teachers Study
      cohort.
AB  - PURPOSE: Information on the role of dietary patterns and endometrial cancer risk
      is limited. We investigated whether dietary patterns are associated with
      endometrial cancer risk among women in the California Teachers Study cohort.
      METHODS: Among 75,093 eligible women, 937 developed invasive endometrial cancer
      between 1995 and 2011. Multivariate Cox regression was performed to estimate
      relative risks (RR) and 95% confidence intervals (CI) associated with five
      dietary patterns identified by principal components factor analysis: "plant
      based," "high protein/high fat," "high carbohydrates," "ethnic," and "salad and
      wine." RESULTS: These dietary patterns were not associated with endometrial
      cancer risk overall (RR = 0.91, 95% CI: 0.72, 1.15 for the highest vs. lowest
      quintile of the "plant-based" dietary pattern) or by menopausal status and
      hormone therapy use. CONCLUSIONS: Dietary patterns do not seem to be associated
      with endometrial cancer risk.

PMID- 25761410
TI  - Plasma lipid levels and colorectal adenoma risk.
AB  - PURPOSE: Abnormalities in lipid levels have been associated with colorectal
      neoplasm risk; however, few studies have adjusted for use of cholesterol-lowering
      medications. The objective of this study was to determine the association of
      plasma lipid levels with adenoma risk while accounting for statin medication use.
      METHODS: We included 254 subjects with advanced adenoma, 246 with single small
      adenoma, 179 with multiple small adenoma cases, and 403 control participants in
      the Tennessee Colorectal Polyp Study who also had plasma lipid measurements
      performed. Data on the use of statin medications were available for 83.4% of
      these participants. The association between plasma lipids and adenoma risk was
      evaluated using logistic regression models. RESULTS: Participants in the highest
      quartile of HDL cholesterol (range 52-106 mg/dl) had an adjusted odds ratio of
      0.49 (95% CI 0.23, 1.07), 0.35 (95% CI 0.13, 0.91), and 0.22 (95% CI 0.09, 0.54)
      for single small, multiple small, and advanced adenomas compared to the lowest
      quartile (range 12-34 mg/dl), respectively. Participants with the highest
      quartile of triglyceride levels (range 178-721 mg/dl) had an adjusted odds ratio
      of 2.40 (95% CI 1.26, 4.55), 1.67 (95% CI 0.66, 4.23), and 2.79 (95% CI 1.25,
      6.23) for single small, multiple small, and advanced adenoma, respectively,
      compared to the lowest quartile (range 40-84 mg/dl). When restricted to
      individuals with known statin medication use, adjusting for statin use did not
      appreciably affect these results. CONCLUSION: We found a direct association
      between triglyceride plasma levels and an inverse association between plasma HDL
      cholesterol levels and adenoma risk. Both effects were not appreciably changed
      when accounting for the regular use of statin medication.

PMID- 25761411
TI  - Rhipicephalus rossicus, a neglected tick at the margin of Europe: a review of its
      distribution, ecology and medical importance.
AB  - Rhipicephalus rossicus (Ixodida: Ixodidae) is a three-host tick with a broad host
      spectrum that includes wild animals, pets, livestock and humans. Despite its
      local abundance in certain areas, most of the available information on R.
      rossicus was published decades ago, mainly by former soviet authors. Its
      distribution largely overlaps the Eurasian steppe. However, its range may be more
      extensive than is currently known because this species may have been
      misidentified as Rhipicephalus sanguineus, principally in areas where the latter
      species is present. Although R. rossicus has been occasionally reported to feed
      on people, little attention has been given to its medical importance. It has been
      shown to have a vectorial role in the transmission of Francisella tularensis,
      Crimean-Congo haemorrhagic fever virus and West Nile virus. However, the
      vectorial importance of R. rossicus may be significantly greater, mainly as the
      closely related species R. sanguineus s.l. is known to transmit a very wide
      spectrum of pathogens. The probably underestimated vectorial role of R. rossicus
      may represent a hidden public health threat. 

PMID- 25761412
TI  - Changes in mitochondrial morphology induced by calcium or rotenone in primary
      astrocytes occur predominantly through ros-mediated remodeling.
AB  - Morphological changes in mitochondria have been primarily attributed to fission
      and fusion, while the more pliable transformations of mitochondria (remodeling,
      rounding, or stretching) have been largely overlooked. In this study, we quantify
      the contributions of fission and remodeling to changes in mitochondrial
      morphology induced by the Ca(2+) ionophore 4Br-A23187 and the metabolic toxin
      rotenone. We also examine the role of reactive oxygen species (ROS) in the
      regulation of mitochondrial remodeling. In agreement with our previous studies,
      mitochondrial remodeling, not fission, is the primary contributor to Ca(2+) 
      mediated changes in mitochondrial morphology induced by 4Br-A23187 in rat
      cortical astrocytes. Treatment with rotenone produced similar results. In both
      paradigms, remodeling was selectively blocked by antioxidants whereas fission was
      not, suggesting a ROS-mediated mechanism for mitochondrial remodeling. In support
      of this hypothesis, inhibition of endogenous ROS by overnight incubation in
      antioxidants resulted in elongated reticular networks of mitochondria.
      Examination of inner and outer mitochondrial membranes revealed that they largely
      acted in concert during the remodeling process. While mitochondrial morphology is
      traditionally ascribed to a net output of fission and fusion processes, in this
      study we provide evidence that the acute pliability of mitochondria can be a
      dominant factor in determining their morphology. More importantly, our results
      suggest that the remodeling process is independently regulated through a ROS
      signaling mechanism. Mitochondrial morphology is traditionally ascribed to a
      balance of fission and fusion processes. We have shown that mitochondria can
      undergo more pliable transformations; remodeling, rounding, or stretching. We
      demonstrate that remodeling, not fission, is the primary contributor to calcium
      mediated changes in mitochondrial morphology in primary astrocytes. Others have
      shown fission is mediated by calcineurin. Our results suggest the remodeling
      process distinct from fission and is independently regulated through a ROS
      signaling mechanism (CsA: Cyclosporine A; NAC: N-acetyl-l-cysteine; GSH: Reduced
      L-Glutathione). 

PMID- 25761413
TI  - Resveratrol induces brown-like adipocyte formation in white fat through
      activation of AMP-activated protein kinase (AMPK) alpha1.
AB  - OBJECTIVE: Development of brown-like/beige adipocytes in white adipose tissue
      (WAT) helps to reduce obesity. Thus we investigated the effects of resveratrol, a
      dietary polyphenol capable of preventing obesity and related complications in
      humans and animal models, on brown-like adipocyte formation in inguinal WAT
      (iWAT). METHODS: CD1 female mice (5-month old) were fed a high-fat diet
      with/without 0.1% resveratrol. In addition, primary stromal vascular cells
      separated from iWAT were subjected to resveratrol treatment. Markers of brown
      like (beige) adipogenesis were measured and the involvement of AMP-activated
      protein kinase (AMPK) alpha1 was assessed using conditional knockout. RESULTS:
      Resveratrol significantly increased mRNA and/or protein expression of brown
      adipocyte markers, including uncoupling protein 1 (UCP1), PR domain-containing
      16, cell death-inducing DFFA-like effector A, elongation of very long-chain fatty
      acids protein 3, peroxisome proliferator-activated receptor-gamma coactivator
      1alpha, cytochrome c and pyruvate dehydrogenase, in differentiated iWAT stromal
      vascular cells (SVCs), suggesting that resveratrol induced brown-like adipocyte
      formation in vitro. Concomitantly, resveratrol markedly enhanced AMPKalpha1
      phosphorylation and differentiated SVC oxygen consumption. Such changes were
      absent in cells lacking AMPKalpha1, showing that AMPKalpha1 is a critical
      mediator of resveratrol action. Resveratrol also induced beige adipogenesis in
      vivo along with the appearance of multiocular adipocytes, increased UCP1
      expression and enhanced fatty acid oxidation. CONCLUSIONS: Resveratrol induces
      brown-like adipocyte formation in iWAT via AMPKalpha1 activation and suggest that
      its beneficial antiobesity effects may be partly due to the browning of WAT and,
      as a consequence, increased oxygen consumption.

PMID- 25761415
TI  - Bayesian inference for low-rank Ising networks.
AB  - Estimating the structure of Ising networks is a notoriously difficult problem. We
      demonstrate that using a latent variable representation of the Ising network, we
      can employ a full-data-information approach to uncover the network structure.
      Thereby, only ignoring information encoded in the prior distribution (of the
      latent variables). The full-data-information approach avoids having to compute
      the partition function and is thus computationally feasible, even for networks
      with many nodes. We illustrate the full-data-information approach with the
      estimation of dense networks. 

PMID- 25761414
TI  - Paediatric arterial ischaemic stroke and cerebral sinovenous thrombosis. First
      report from the Italian Registry of Pediatric Thrombosis (R. I. T. I., Registro
      Italiano Trombosi Infantili).
AB  - Data from large case series of children with cerebral thrombotic events are
      pivotal to improve prevention, early recognition and treatment of these
      conditions. The Italian Registry of Pediatric Thrombosis (R. I. T. I.) was
      established in 2007 by a multidisciplinary team, aiming for a better
      understanding of neonatal and paediatric thrombotic events in Italy and providing
      a preliminary source of data for the future development of specific clinical
      trials and diagnostic-therapeutic protocols. We analysed data relative to the
      paediatric cerebral thrombotic events of the R. I. T. I. which occurred between
      January 2007 and June 2012. In the study period, 79 arterial ischaemic stroke
      (AIS) events (49 in males) and 91 cerebral sinovenous thrombosis (CSVT) events
      (65 in males) were enrolled in the R. I. T. I. Mean age at onset was 4.5 years in
      AIS, and 7.1 years in CSVT. Most common modes of presentation were hemiparesis,
      seizures and speech disturbances in AIS, and headache, seizures and lethargy in
      CSVT. Most common etiologies were underlying chronic diseases, vasculopathy and
      cardiopathy in AIS, and underlying chronic diseases and infection in CSVT. Time
      to diagnosis exceeded 24 hours in 46 % AIS and 59 % CSVT. Overall data from the
      Italian Registry are in substantial agreement with those from the literature,
      despite small differences. Among these, a longer time to diagnosis compared to
      other registries and case series poses the accent to the need of an earlier
      recognition of paediatric cerebrovascular events in Italy, in order to enable
      prompt and effective treatment strategies. 

PMID- 25761417
TI  - Spindle cell squamous cell carcinoma arising from verrucous hyperplasia during
      BRAF inhibitor therapy for melanoma.

PMID- 25761416
TI  - Correlating high-resolution magic angle spinning NMR spectroscopy and gene
      analysis in osteoarthritic cartilage.
AB  - Osteoarthritis (OA) is a common multifactorial and heterogeneous degenerative
      joint disease, and biochemical changes in cartilage matrix occur during the early
      stages of OA before morphological changes occur. Thus, it is desired to measure
      regional biochemical changes in the joint. High-resolution magic angle spinning
      (HRMAS) NMR spectroscopy is a powerful method of observing cartilaginous
      biochemical changes ex vivo, including the concentrations of alanine and N
      acetyl, which are markers of collagen and total proteoglycan content,
      respectively. Previous studies have observed significant changes in chondrocyte
      metabolism of OA cartilage via the altered gene expression profiles of ACAN,
      COL2A1 and MMP13, which encode aggrecan, type II collagen and matrix
      metalloproteinase 13 (a protein crucial in the degradation of type II collagen),
      respectively. Employing HRMAS, this study aimed to elucidate potential
      relationships between N-acetyl and/or alanine and ACAN, COL2A1 and/or MMP13
      expression profiles in OA cartilage. Thirty samples from the condyles of five
      subjects undergoing total knee arthroplasty to treat OA were collected. HRMAS
      spectra were obtained at 11.7 T for each sample. RNA was subsequently extracted
      to determine gene expression profiles. A significant negative correlation between
      N-acetyl metabolite and ACAN gene expression levels was observed; this provides
      further evidence of N-acetyl as a biomarker of cartilage degeneration. The
      alanine doublet was distinguished in the spectra of 15 of the 30 specimens of
      this study. Alanine can only be detected with HRMAS NMR spectroscopy when the
      collagen framework has been degraded such that alanine is sufficiently mobile to
      form a distinguished peak in the spectrum. Thus, HRMAS NMR spectroscopy may
      provide unique localized measurements of collagenous degeneration in OA
      cartilage. The identification of imaging markers that could provide a link
      between OA pathology and chondrocyte metabolism will facilitate the development
      of more sensitive diagnostic techniques and will improve methods of monitoring
      treatment for patients suffering from OA.

PMID- 25761418
TI  - Shish-kebab-structured poly(epsilon-caprolactone) nanofibers hierarchically
      decorated with chitosan-poly(epsilon-caprolactone) copolymers for bone tissue
      engineering.
AB  - In this work, scaffolds with a shish-kebab (SK) structure formed by poly(epsilon
      caprolactone) (PCL) nanofibers and chitosan-PCL (CS-PCL) copolymers were prepared
      via electrospinning and subsequent crystallization for bone tissue engineering
      applications. The aim of this study was to introduce nanosized topography and the
      high biocompatibility of chitosan onto PCL nanofibers to enhance cell affinity to
      PCL scaffolds. CS-PCL copolymers with various ratios were synthesized, and then
      spontaneously crystallized as kebabs onto the electrospun PCL fibers, which acted
      as shishes. Scanning electron microscopy (SEM) results demonstrated that the
      copolymer with PCL to chitosan ratio of 8.8 could hierarchically decorate the PCL
      nanofibers and formed well-shaped kebabs on the PCL nanofiber surface. Water
      contact angle tests and biomimetic activity experiments revealed that the shish
      kebab scaffolds with CS-PCL kebabs (PCL-SK(CS-PCL(8.8))) showed enhanced
      hydrophilicity and mineralization ability compared with smooth PCL and PCL
      SK(PCL) shish-kebab scaffolds. Osteoblast-like MG63 cells cultured on the PCL
      SK(CS-PCL(8.8)) scaffolds showed optimizing cell attachment, cell viability, and
      metabolic activity, demonstrating that this kind of scaffold has potential
      applications in bone tissue engineering.

PMID- 25761419
TI  - The complete mitochondrial genome of the Onychostoma gerlachi (Cypriniformes,
      Cyprinidae).
AB  - Onychostoma gerlachi, which belongs to the genus Onychostoma (Cypriniformes,
      Cyprinidae), is an economic fish that inhabits the flowing freshwater in south of
      China. The complete mitochondrial genome of O. gerlachi was determined to be
      16,601 bp long circular molecule with a typical gene arrangement of vertebrate
      mitochondrial DNA. It includes 13 protein-coding genes, 22 transfer RNA genes, 2
      ribosomal RNA genes and a non-coding control region (D-loop). The overall base
      composition of O. gerlachi is 31.38% for A, 24.24% for T, 28.29% for C and 16.09%
      for G, with a slight AT bias of 55.62%. The complete mtDNA genome sequence of O.
      gerlachi obtained in this study provides fundamental data for studying genetic
      diversity and phylogenetics on this species.

PMID- 25761420
TI  - Fukushima radionuclides in the NW Pacific, and assessment of doses for Japanese
      and world population from ingestion of seafood.
AB  - Variations of Fukushima-derived radionuclides ((90)Sr, (134)Cs and (137)Cs) in
      seawater and biota offshore Fukushima and in the NW Pacific Ocean were
      investigated and radiation doses to the Japanese and world population from
      ingestion of seafood contaminated by Fukushima radionuclides were estimated and
      compared with those from other sources of anthropogenic and natural
      radionuclides. The total effective dose commitment from ingestion of
      radionuclides in fish, shellfish and seaweed caught in coastal waters off
      Fukushima was estimated to be 0.6 +/- 0.4 mSv/y. The individual effective dose
      commitment from consumption of radioactive-contaminated fish caught in the open
      Pacific Ocean was estimated to be 0.07 +/- 0.05 mSv/y. These doses are comparable
      or much lower than doses delivered from the consumption of natural (210)Po in
      fish and in shellfish (0.7 mSv/y). The estimated individual doses have been below
      the levels when any health damage of the Japanese and world population could be
      expected.

PMID- 25761421
TI  - Reactivity indices for natural bond orbitals: a new methodology.
AB  - A new reactivity index has been defined; this parameter is focused on a
      molecule's natural bond orbitals (NBOs) and derives in a natural way from Fukui
      functions. NBOs have the advantage of being very localized, allowing the reaction
      site of an electrophile or nucleophile to be determined within a very precise
      molecular region. Finally, the indices for a representative set of organic
      molecules were calculated and their usefulness tested on some protonation
      reactions. 

PMID- 25761422
TI  - Comparative theoretical investigation of the structures, energetics, and
      stabilities of C7N5H11cages.
AB  - Carbon-nitrogen cages are the focus of much research due to their potential use
      as high energy density materials (HEDMs). Several such cage isomers of C7N5H11,
      created by modifying the most stable N12 cage, were examined by performing
      theoretical calculations to evaluate their suitability as potential HEDMs.
      Calculations were carried out with density functional theory and Moller-Plesset
      perturbation theory (MP2) using the basis sets 6-31+G(d,p) and cc-pvdz. The
      relative thermodynamic stabilities of the isomers were explored in two ways: (1)
      the thermodynamic stability of one isomer was compared to that of another isomer
      based on their relative energies; (2) the kinetic stabilities of the isomers were
      determined by calculating the corresponding bond-breaking energies.

PMID- 25761424
TI  - Cranial Accelerometry Can Detect Cerebral Vasospasm Caused by Subarachnoid
      Hemorrhage.
AB  - BACKGROUND: We previously reported the presence of a cranial "bruit" in patients
      with cerebral vasospasm by signal processing cranial accelerometry signals time
      locked to the cardiac cycle. This shift to higher frequencies is likely related
      to the turbulence of blood flow produced by vascular narrowing. We sought to
      build a more quantitative model to predict cerebral vasospasm then test the
      accuracy of this technique to detect cerebral vasospasm in a prospective blinded
      study. METHODS: Skull accelerometry was performed using an array of 6 highly
      sensitive accelerometers placed in contact with the scalp. Paired transcranial
      Doppler (TCD) recordings and accelerometry epochs were obtained in consecutive
      patients with subarachnoid hemorrhage undergoing TCD recordings for surveillance
      of cerebral vasospasm. The energy of rectified acceleration measurements within
      systolic and diastolic bands of the cardiac cycle were measured and correlated
      with TCD-defined spasm. This model was then tested prospectively in a blinded
      consecutive sample of subarachnoid hemorrhage patients to determine accuracy of
      the technique. RESULTS: We developed a model predicting cerebral vasospasm from
      analysis of 14 unblinded subjects with varying degrees of cerebral vasospasm as
      detected by TCD. We then recorded from 58 subjects obtaining 125-paired
      recordings of accelerometry and TCD to test this model in a blinded analysis.
      Accelerometry detection of any spasm versus non-spasm correlated with TCD-defined
      vasospasm (P < 0.001). The model was 81 % sensitive for detecting any cerebral
      vasospasm in patients, while the negative predictive value was 61 %. CONCLUSION:
      Highly sensitive skull accelerometry can detect cerebral vasospasm with
      clinically meaningful accuracy. This tool holds promise in the ICU environment to
      detect as well as reject cerebral vasospasm as the cause of neurological deficits
      in subarachnoid hemorrhage.

PMID- 25761423
TI  - Molecular mechanisms of the formation and progression of intracranial aneurysms.
AB  - Until recently, only a little was understood about molecular mechanisms of the
      development of an intracranial aneurysm (IA). Recent advancements over the last
      decade in the field of genetics and molecular biology have provided us a wide
      variety of evidences supporting the notion that chronic inflammation is closely
      associated with the pathogenesis of IA development. In the field of genetics,
      large-scale Genome-wide association studies (GWAS) has identified some IA
      susceptible loci and genes related to cell cycle and endothelial function.
      Researches in molecular biology using human samples and animal models have
      revealed the common pathway of the initiation, progression, and rupture of IAs.
      IA formation begins with endothelial dysfunction followed by pathological
      remodeling with degenerative changes of vascular walls. Medical treatments
      inhibiting inflammatory cascades in IA development are likely to prevent IA
      progression and rupture. Statins and aspirin are expected to suppress IA
      progression by their anti-inflammatory effects. Decoy oligodeoxynucleotides
      (ODNs) inhibiting inflammatory transcription factors such as nuclear factor kappa
      B (NF-kappaB) and Ets-1 are the other promising choice of the prevention of IA
      development. Further clarification of molecular mechanisms of the formation and
      progression of IAs will shed light to the pathogenesis of IA development and
      provide insight into novel diagnostic and therapeutic strategies for IAs. 

PMID- 25761425
TI  - Augmented Renal Clearance in Patients with Subarachnoid Hemorrhage.
AB  - BACKGROUND: Patients with subarachnoid hemorrhage (SAH) typically exhibit
      hyperdynamic cardiovascular hemodynamics, which may lead to increased medication
      clearance. The aims of this study were to evaluate the actual creatinine
      clearance (CrClA) in an aneurysmal SAH population and the effect of the
      development of cerebral vasospasm (CV) along with its treatment to better
      understand if this population exhibits augmented renal clearance (ARC). METHODS:
      This was a prospective, single-center study in a neurosciences ICU at a
      university hospital. A total of 20 patients were consented and provided a 24-h
      urine sample to measure the CrClA. If patients experienced CV, a 24-h urine
      collection was repeated during vasospasm treatment. CrClA was measured using a
      modified Jaffe assay. RESULTS: Among the 20 patients enrolled, the mean SAH CrClA
      was 325.93 +/- 135.20 ml/min 1.73 m(2) and this differed significantly from the
      SAH estimated creatinine clearance (CrClE) 144.93 +/- 42.82 ml/min 1.73 m(2) (p <
      0.001). Four patients developed CV; the mean CV CrClA was 558.43 +/- 356.12
      ml/min 1.73 m(2) and there was no significant difference when compared to those
      patients' mean SAH CrClA (246.91 +/- 84.14 ml/min 1.73 m(2), p = 0.16).
      CONCLUSIONS: ARC was present in 100 % of the patients with recent SAH enrolled.
      Although ARC remained present in the patients who experienced CV, their
      creatinine clearance was not significantly further augmented. Further work is
      needed to clarify the impact of such clearances on renally excreted medications
      and how the development and treatment of CV further augment these findings.

PMID- 25761426
TI  - Admission Leukocytosis in Intracerebral Hemorrhage: Associated Factors and
      Prognostic Implications.
AB  - BACKGROUND AND PURPOSE: Leukocytosis is a reaction that is usually, but not
      always, associated with an infectious process. There is very little data on the
      significance of admission leukocytosis (AL) in patients with intracerebral
      hemorrhage (ICH). The purpose of this study was to investigate the associated
      clinical and radiologic findings and prognostic significance of AL in patients
      with ICH. METHODS: We retrospectively reviewed the records of consecutive ICH
      patients admitted over a 2-year period. Key data we collected included ICH size,
      location, intraventricular hemorrhage (IVH), age, admission Glasgow Coma Scale
      (GCS0) score, peak leukocyte count and temperature in the first 24 h of
      hospitalization, and outcomes on discharge. Severity of IVH was calculated using
      the Graeb Scale. Logistic regression was performed to determine association of
      variables. RESULTS: In 128 consecutive ICH patients, AL was present in 41.4 %. AL
      was significantly associated with presence (OR 2.28, 95 % CI 1.11-4.68; p =
      0.024), but not severity of IVH and with admission GCS0. Leukocyte count showed a
      strong association with IVH (p = 0.01) and with decreasing GCS0 (p = 0.007).
      There was no correlation between AL and poor outcome at discharge. There was also
      no evidence of infection in any patient with AL. CONCLUSION: AL in ICH patients
      is often non-infectious, strongly associated with the presence of IVH, but not
      specifically an ominous indicator for outcome. Leukocyte count has an inverse
      relationship with GCS0. Prospective studies are needed to confirm these findings.

PMID- 25761427
TI  - The Activation of NF-kappaB in Infiltrated Mononuclear Cells Negatively
      Correlates with Treg Cell Frequency in Oral Lichen Planus.
AB  - Oral lichen planus (OLP) is a T cell-mediated chronic inflammatory mucosal
      disease with persistent accumulation of T cells in the lamina propria. Nuclear
      factor-kappa B (NF-kappaB) is a major regulator of immune responses, and NF
      kappaB-dependent cytokines and pro-inflammatory mediators can be detected in
      higher levels in the saliva and serum from patients with OLP.
      CD4(+)CD25(+)Foxp3(+) regulatory T (Treg) cells play an important role in the
      prevention of autoimmune pathology by regulating the immune response. To explore
      the correlation between NF-kappaB p65 activation and accumulation of Treg cells
      in patients with OLP, 40 ethnic Chinese patients with OLP and 10 healthy
      volunteers were recruited. The nuclear expression of NF-kappaB p65 in infiltrated
      mononuclear cells and Treg cells in the OLP lesion and the normal oral mucosa
      (NOM) was analyzed by immunohistochemistry assay. Our results showed that both
      the nuclear expression of NF-kappaB p65 and the number of Foxp3(+) Treg were
      higher in the OLP lesions. Furthermore, the frequency of Treg cells was
      negatively correlated with NF-kappaB nuclear expression in subepithelial
      lymphocytic infiltrate of the OLP lesion. This finding provides a new insight
      into the pathogenesis of OLP and may contribute to novel therapeutic strategies
      for the treatment of OLP by modulating the immune system. 

PMID- 25761428
TI  - No Strong Relationship Between Components of the Lectin Pathway of Complement and
      Susceptibility to Pulmonary Tuberculosis.
AB  - Mycobacterium tuberculosis (TB) may utilise the lectin complement pathway to
      facilitate entry into its niche within macrophages. Previous studies examining
      mannose-binding lectin (MBL) in patients with TB have been limited by failure to
      correlate genotype/phenotype relationships. This study investigated serum levels
      and genotypes of MBL, Ficolin-2, Ficolin-3 and MASP-2 in 168 patients with
      pulmonary tuberculosis and 168 age/sex-matched controls. Low serum levels of MBL
      and Ficolin-2 were defined using cut-offs previously identified in the
      literature. Median MBL serum levels were higher in TB patients than controls-1400
      ng/ml (IQR 435-2520) vs 1030 ng/ml (350-2050), p = 0.02-but this was not mirrored
      by a difference in MBL haplotype frequencies (MBL deficient haplotypes were
      observed in 11.9 % of TB patients and 11.3 % of controls). Severe Ficolin-2
      deficiency (<1200 ng/ml) was more frequent in TB than controls (7.1 vs 3.0 %,
      odds ratio 2.51 95 % CI 0.86-7.28, p = 0.1) but the difference was not
      statistically significant. No relationship between Ficolin-2, Ficolin-3 or MASP-2
      genotypes or serum levels and TB were observed. No strong relationship between
      the lectin complement pathway and pulmonary tuberculosis was observed. Previous
      data linking high MBL serum levels with TB were likely due to an acute phase
      response rather than a true effect on disease susceptibility. 

PMID- 25761429
TI  - Pentraxin-3 Attenuates Renal Damage in Diabetic Nephropathy by Promoting M2
      Macrophage Differentiation.
AB  - As one of the most important long-term complications of diabetes, diabetic
      nephropathy (DN) is the major cause of end-stage renal disease and high mortality
      in diabetic patients. The long pentraxin 3 (Ptx3) is a member of a superfamily of
      conserved proteins characterized by a cyclic multimeric structure and a conserved
      C-terminal domain. Several clinical investigations have demonstrated that
      elevated plasma Ptx3 levels are associated with cardiovascular and chronic kidney
      diseases (CKD). However, the therapeutic effect of Ptx3 on DN has never been
      investigated. In our current study, we showed a crucial role for Ptx3 in
      attenuating renal damage in DN. In our mouse hyperglycemia-induced nephropathy
      model, Ptx3 treatment showed significantly increased expression of nephrin,
      acetylated nephrin, and Wilm's tumor-1 protein (WT-1) when compared with control.
      The number of CD4(+) T cells, CD8(+) T cells, Ly6G(+) neutrophils, and CD11b(+)
      macrophages were all significantly lower in the Ptx3-treated group than that in
      the control group in DN. The IL-4 and IL-13 levels in the Ptx3-treated group were
      markedly higher than that in the control group in DN. Correspondingly, the Ptx3
      treated group showed increased numbers of Arg1- or CD206-expressing macrophages
      compared with the control group. Furthermore, inhibition of Ptx3-treated
      macrophages abrogated the alleviated renal damage induced by Ptx3 treatment. In
      conclusion, Ptx3 attenuates renal damage in DN by promoting M2 macrophage
      differentiation. 

PMID- 25761430
TI  - Comparison of the pharmacodynamic effects of ranolazine versus amlodipine on
      platelet reactivity in stable patients with coronary artery disease treated with
      dual antiplatelet therapy : The ROMAN (RanOlazine vs. aMlodipine on platelet
      reactivity in stable patients with CAD treated with dual ANtiplatelet therapy)
      study.
AB  - Amlodipine, commonly used for relief of ischemic symptoms in coronary artery
      disease (CAD), may affect clopidogrel-induced antiplatelet effects. It remains
      unknown if ranolazine, an antianginal drug that constitutes a pharmacologic
      alternative to calcium channel blockade, interferes with clopidogrel-induced
      antiplatelet effects. The aim of the ROMAN study was to compare the
      pharmacodynamic effects of ranolazine versus amlodipine on platelet reactivity in
      clopidogrel treated patients with CAD. A prospective, randomized, cross-over,
      open-label study conducted in a total of 210 CAD patients on aspirin (100
      mg/q.d.) and clopidogrel (75 mg/q.d.) 1 month following percutaneous coronary
      intervention. Patients were randomly assigned to amlodipine (10 mg p.d., n = 105)
      or ranolazine (750 mg b.i.d., n = 105) for 15 days, and after a 1-week wash-out
      period, crossed-over treatment for 15 days. P2Y12 reaction units (PRU) were
      assessed at baseline and after each treatment sequence. High on-treatment
      platelet reactivity (HPR) was defined as a PRU > 208. Amlodipine was associated
      with higher PRU than ranolazine (182 +/- 75 vs. 167 +/- 64, p = 0.028). As
      compared with baseline, PRU increased significantly after treatment with
      amlodipine (p = 0.018), but was not different after ranolazine therapy (p =
      0.871). Changes in platelet reactivity following amlodipine therapy appeared to
      depend on baseline HPR status, as PRU levels significantly increased only among
      HPR subjects. In stable CAD patients treated with dual antiplatelet therapy after
      PCI, concomitant treatment with amlodipine, but not ranolazine, interferes with
      clopidogrel-induced antiplatelet effects.

PMID- 25761431
TI  - Dyspepsia in the community: value of a community-based mailed survey to identify
      potential participants for a randomized clinical trial.
AB  - OBJECTIVE: To assess the usefulness of a community-based mailed survey to
      identify participants with functional dyspepsia (FD) for a clinical trial.
      MATERIAL AND METHODS: In 2008, a valid self-report questionnaire of
      gastrointestinal symptoms required for diagnosis of FD was mailed to randomly
      selected cohorts of Olmsted County, Minnesota, residents. From survey responses
      (54%), FD cases and controls were identified. Phone calls were completed in 2010
      and 2011 to 54% of respondents offering participation to those meeting criteria.
      RESULTS: Of 937 people identified from the survey, 189 cases and 265 controls
      were contacted by phone using four questions similar to the written survey
      resulting in a moderate level of agreement (Kappa 0.43, 95% CI: 0.35- 0.51; p =
      0.11). The proportion reporting FD symptoms by survey was 42%, while the
      proportion by phone was 38%. Comparing classification of cases and controls, 118
      (62%) survey cases had dyspepsia symptoms on phone screening while 53 (20%) of
      the survey controls reported FD symptoms. Of 171 who had symptoms, 60 (35%)
      declined, 33 (19%) were over study age limit, 24 (14%) had inadequate symptom
      levels and 36 (21%) had comorbidities. Of survey respondents contacted, six (3%)
      people were enrolled with two screen fails resulting in four (1%) randomized.
      CONCLUSION: Agreement between survey and phone questions was modest.
      Classifications between case and control changed. People eligible and willing to
      participate were a fraction of people reporting symptoms. People participating in
      clinical trials do not broadly represent those in the population.

PMID- 25761433
TI  - An efficient multiple healing conductive composite via host-guest inclusion.
AB  - A self-healable conductive composite is developed by combining the small
      molecules and nanotubes through host-guest interactions. This material shows
      uniform conductivity, microwave absorption and humidity sensing properties, and
      can be rapidly healed to over 90% electrical and mechanical properties with the
      aid of water multiple times. In addition, the produced material is also
      remouldable and recyclable. 

PMID- 25761432
TI  - Enhancing our understanding of current therapies for hepatitis C virus (HCV).
AB  - Great progress has been made in understanding the HCV genome and its molecular
      virology. This understanding has culminated in the development of direct-acting
      antiviral (DAA) agents targeting HCV viral proteins. Telaprevir (TVR) and
      boceprevir (BOC) were the first DAAs introduced for treatment of genotype 1 HCV
      in 2011; when used in combination with pegylated interferon (pegIFN) and
      ribavirin (RBV), these protease inhibitors improved efficacy in patients with
      chronic HCV infection compared to the traditional dual therapy. However, this
      combination was associated with adverse events that often led to early
      termination of therapy. In late 2013, the FDA approved a second wave of DAAs,
      sofosbuvir (SOF) and simeprevir (SMV). The use of SOF with SMV opened the door
      for IFN-free combination regimens. This combination was highly efficacious and
      well tolerated in patients with HCV genotype 1. Sofosbuvir and ledipasvir (LDV)
      fixed-dose oral combination (FDC) therapy, and paritaprevir/ritonavir, ombitasvir
      and dasabuvir +/- RBV were recently approved, elevating sustained virologic
      response (SVR) rates to over 95 %. We are anticipating the approval of additional
      IFN-free regimens with comparable efficacy and tolerability but with the addition
      of pangenotypic coverage, fewer drug-drug interactions, and a high barrier to
      resistance. This review will summarize current management for chronic HCV
      infection. 

PMID- 25761434
TI  - Switching of oral bisphosphonates to denosumab in chronic glucocorticoid users: a
      12-month randomized controlled trial.
AB  - OBJECTIVES: To evaluate the effect of switching from oral bisphosphonates to
      denosumab on bone mineral density (BMD) in long-term glucocorticoid users.
      METHODS: Adult patients who were receiving long-term prednisolone (>=2.5 mg/day
      for >=1 year) and oral bisphosphonates (>=2 years) were recruited. Participants
      were randomized to either continue oral bisphosphonates or switch to denosumab
      (60 mg subcutaneously every 6 months) for 12 months. Serial BMD (lumbar spine,
      hip) and bone turnover markers (serum osteocalcin, P1NP, beta-CTX) were measured.
      RESULTS: 42 women were recruited (age 54.7+/-12.9 years; 21 shifted to denosumab
      and 21 continued on bisphosphonates). The duration of prednisolone therapy was
      101+/-66.3 months and the daily dose was 4.4+/-2.1 mg. Baseline demographic data,
      osteoporosis risk factors, and BMD at various sites were similar between the two
      groups of patients. At month 12, BMD of the spine and hip increased by +3.4+/
      0.9% (p=0.002) and +1.4+/-0.6% (p=0.03), respectively, in the denosumab group;
      whereas the corresponding change was +1.5+/-0.4% (p=0.001) and +0.80+/-0.5%
      (p=0.12) in the bisphosphonate group. The spinal BMD at month 12 was
      significantly higher in the denosumab than bisphosphonate group after adjustment
      for baseline BMD and beta-CTX values, and other confounding factors (p=0.01).
      Bone turnover markers (beta-CTX and P1NP) were more strongly suppressed by
      denosumab than the bisphosphonates. Minor infections were more common in
      denosumab-treated patients while other adverse events occurred at similar
      frequencies between the two groups. CONCLUSIONS: In patients receiving long-term
      glucocorticoids, switching from oral bisphosphonates to denosumab resulted in
      greater gain of the spinal BMD and suppression of bone turnover markers after 12
      months of therapy. The results have to be confirmed by a larger clinical trial
      with fracture as endpoint.

PMID- 25761435
TI  - Highly PEGylated DNA Nanoparticles Provide Uniform and Widespread Gene Transfer
      in the Brain.
AB  - Gene delivery to the central nervous system (CNS) has potential as a means for
      treating numerous debilitating neurological diseases. Nonviral gene vector
      platforms are tailorable and can overcome key limitations intrinsic to virus
      mediated delivery; however, lack of clinical efficacy with nonviral systems to
      date may be attributed to limited gene vector dispersion and transfection in
      vivo. It is shown that the brain extracellular matrix (ECM) strongly limits
      penetration of polymer-based gene vector nanoparticles (NP) through the brain
      parenchyma, even when they are very small (<60 nm) and coated with a polyethylene
      glycol (PEG) corona of typical density. Following convection enhanced delivery
      (CED), conventional gene vectors are confined to the injection site, presumably
      by adhesive interactions with the brain ECM and do not provide gene expression
      beyond the point of administration. In contrast, it is found that incorporating
      highly PEGylated polymers allows the production of compacted (~43 nm) and
      colloidally stable DNA NP that avoid adhesive trapping within the brain
      parenchyma. When administered by CED into the rat striatum, highly PEGylated DNA
      NP distribute throughout and provide broad transgene expression without vector
      induced toxicity. The use of these brain-penetrating gene vectors, in conjunction
      with CED, offers an avenue to improve gene therapy for CNS diseases. 

PMID- 25761437
TI  - Quality of first trimester risk prediction models for pre-eclampsia: a systematic
      review.
AB  - BACKGROUND: There is an increasing interest in first trimester risk prediction
      models for pre-eclampsia. OBJECTIVES: To systematically review and critically
      assess the building and reporting of methods used to develop first trimester risk
      prediction models for pre-eclampsia. SEARCH STRATEGY: Search of PubMed and EMBASE
      databases from inception to July 2013. SELECTION CRITERIA: Logistic regression
      model for predicting the risk of pre-eclampsia in the first trimester, including
      uterine artery Doppler among independent variables. DATA COLLECTION AND ANALYSIS:
      We extracted information on study design, outcome definition, participant
      recruitment, sample size and number of events, risk predictors and their
      selection and treatment, model-building strategies, missing data, overfitting and
      validation. MAIN RESULTS: The initial search identified 80 articles. A total of
      24 studies were eligible for review, from which 38 predictive models were
      identified. The median number of study participants was 697 [interquartile range
      (IQR) 377- 5126]. The median number of cases of pre-eclampsia per model was 37
      (IQR 19-97). The median number of risk predictors was 5 (IQR 3.75-7). In 22% of
      the models, the number of events per variable was fewer than the commonly
      recommended value of 10 events per predictor; this proportion increased to 94% in
      models for early pre-eclampsia. Treatment and handling of missing data were not
      reported in 37 models. Only three models reported model validation. CONCLUSIONS:
      We found frequent methodological deficiencies in studies reporting risk
      prediction models for pre-eclampsia. This may limit their reliability and
      validity.

PMID- 25761436
TI  - Ultrasound observations of subtle movements: a pilot study comparing foetuses of
      smoking and nonsmoking mothers.
AB  - AIM: One way to assess foetal health of smokers is to ask mothers to count
      perceived movements, an unreliable method hiding differences in prenatal
      development. The aim of this pilot study was to assess subtle foetal movements in
      ultrasound scans and establish whether they differ in foetuses of mothers who
      smoked and nonsmoking mothers. METHODS: This longitudinal pilot study recruited
      twenty mothers (16 nonsmoking; 4 smoking) scanned four times from 24 to 36 weeks
      gestation (80 ultrasound scans). Two types of fine-grained movements were coded
      offline and analysed using a Poisson log-linear mixed model. RESULTS: Foetuses of
      smoking mothers showed a significantly higher rate of mouth movements compared to
      foetuses of nonsmoking mothers (p = 0.02), after controlling for maternal stress
      and depression. As pregnancy progressed, these differences between the smoking
      and nonsmoking groups widened. Differences between the two groups in the rate of
      foetal facial self-touch remained constant as pregnancy progressed and were
      borderline significant (p = 0.07). CONCLUSION: Rates of foetal mouth movement and
      facial self-touch differ significantly between smokers and nonsmokers. A larger
      study is needed to confirm these results and to investigate specific effects,
      including the interaction of maternal stress and smoking. Additionally, the
      feasibility of this technique for clinical practice should be assessed.

PMID- 25761438
TI  - The effect of vegetarian diet on skin autofluorescence measurements in
      haemodialysis patients.
AB  - CVD remains the major cause of death for dialysis patients. Dialysis patients
      have both traditional and nontraditional risk factors, including the retention of
      advanced glycation end products (AGE). Tissue AGE can be measured by skin
      autofluorescence (SAF) and are a reliable measurement of chronic exposure.
      Dietary intake of AGE may be lower in vegetarian patients than in non-vegetarian
      patients, so we determined whether vegetarian patients had lower SAF than non
      vegetarian patients. We measured SAF in 332 adult haemodialysis patients using a
      UV technique in a standardised manner. Information about patients' demographic
      data, laboratory results and current medicinal prescriptions was collected
      retrospectively from the hospital's computerised database. The mean patient age
      was 65.2 (SD 15.1) years, 64 % were men, 42 % were diabetic, and 66 % were
      Caucasian. The mean SAF was 3.26 (SD 0.95) arbitrary units (AU), and SAF was
      lower in vegetarians as compared to non-vegetarians (2.71 (SD 0.6) v. 3.31 (SD
      0.97) AU, P= 0.002). SAF was negatively correlated on both univariate (r -0.17,
      P= 0.002) and multiple linear regression (beta coefficient -0.39, 95 % CI -0.7, 
      0.07, P= 0.019). SAF, a marker of tissue AGE deposition, was reduced in
      vegetarian haemodialysis patients after correction for known confounders, which
      suggests that a vegetarian diet may reduce exposure to preformed dietary AGE.
      Dietary manipulation could potentially reduce tissue AGE and SAF as well as CVD
      risk, but further prospective studies are warranted to confirm the present
      findings.

PMID- 25761439
TI  - Sediment toxicity and ecological risk of trace metals from streams surrounding a
      municipal solid waste landfill.
AB  - The present study is an attempt to assess the pollution intensity and
      corresponding ecological risk of heavy metals such as Cd, Ni, Pb, Cu, Zn and Cr
      using various indices like geo-accumulation index, concentration factor,
      pollution loading and ecological risk index. In all 21 surface sediments samples
      were collected from the stream flowing around the solid waste disposal landfill
      of Qayen city in southeastern Iran. Although Igeo values for Cd varied greatly,
      sites 18-21 with class 5 show heavy loads of Cd (values between 4.13 and 4.45).
      PLI values (3.37-12.89) clearly suggest strong contamination with respect to the
      measured metals. This study clearly indicates that the contamination risk in the
      downstream reservoir is much higher than upstream sites due to transfer and
      accumulation of leached metals from upstream to downstream. 

PMID- 25761440
TI  - Surface transfer doping induced effective modulation on ambipolar characteristics
      of few-layer black phosphorus.
AB  - Black phosphorus, a fast emerging two-dimensional material, has been configured
      as field effect transistors, showing a hole-transport-dominated ambipolar
      characteristic. Here we report an effective modulation on ambipolar
      characteristics of few-layer black phosphorus transistors through in situ surface
      functionalization with caesium carbonate (Cs2CO3) and molybdenum trioxide (MoO3),
      respectively. Cs2CO3 is found to strongly electron dope black phosphorus. The
      electron mobility of black phosphorus is significantly enhanced to ~27 cm(2) V(
      1) s(-1) after 10 nm Cs2CO3 modification, indicating a greatly improved electron
      transport behaviour. In contrast, MoO3 decoration demonstrates a giant hole
      doping effect. In situ photoelectron spectroscopy characterization reveals
      significant surface charge transfer occurring at the dopants/black phosphorus
      interfaces. Moreover, the surface-doped black phosphorus devices exhibit a
      largely enhanced photodetection behaviour. Our findings coupled with the tunable
      nature of the surface transfer doping scheme ensure black phosphorus as a
      promising candidate for further complementary logic electronics. 

PMID- 25761441
TI  - A snapshot of cancer in Chile: analytical frameworks for developing a cancer
      policy.
AB  - INTRODUCTION: The South American country Chile now boasts a life expectancy of
      over 80 years. As a consequence, Chile now faces the increasing social and
      economic burden of cancer and must implement political policy to deliver
      equitable cancer care. Hindering the development of a national cancer policy is
      the lack of comprehensive analysis of cancer infrastructure and economic impact.
      OBJECTIVES: Evaluate existing cancer policy, the extent of national investigation
      and the socio-economic impact of cancer to deliver guidelines for the framing of
      an equitable national cancer policy. METHODS: Burden, research and care-policy
      systems were assessed by triangulating objective system metrics--epidemiological,
      economic, etc.--with political and policy analysis. Analysis of the literature
      and governmental databases was performed. The oncology community was interviewed
      and surveyed. RESULTS: Chile utilizes 1% of its gross domestic product on cancer
      care and treatment. We estimate that the economic impact as measured in
      Disability Adjusted Life Years to be US$ 3.5 billion. Persistent inequalities
      still occur in cancer distribution and treatment. A high quality cancer research
      community is expanding, however, insufficient funding is directed towards
      disproportionally prevalent stomach, lung and gallbladder cancers. CONCLUSIONS:
      Chile has a rapidly ageing population wherein 40% smoke, 67% are overweight and
      18% abuse alcohol, and thus the corresponding burden of cancer will have a
      negative impact on an affordable health care system. We conclude that the Chilean
      government must develop a national cancer strategy, which the authors outline
      herein and believe is essential to permit equitable cancer care for the country.

PMID- 25761442
TI  - Pragmatism, dynamism and flexibility in research and clinical practice.

PMID- 25761443
TI  - Concentrations and delta2H values of cuticular n-alkanes vary significantly among
      plant organs, species and habitats in grasses from an alpine and a temperate
      European grassland.
AB  - n-Alkanes are long-chained hydrocarbons contained in the cuticle of terrestrial
      plants. Their hydrogen isotope ratios (delta(2)H) have been used as a proxy for
      environmental and plant ecophysiological processes. Calibration studies designed
      to resolve the mechanisms that determine the delta(2)H values of n-alkanes have
      exclusively focused on n-alkanes derived from leaves. It is, however, unclear in
      which quantities n-alkanes are also produced by other plant organs such as roots
      or inflorescences, or whether different plant organs produce distinct n-alkane
      delta(2)H values. To resolve these open questions, we sampled leaves, sheaths,
      stems, inflorescences and roots from a total of 15 species of European C3 grasses
      in an alpine and a temperate grassland in Switzerland. Our data show slightly
      increased n-alkane concentrations and n-alkane delta(2)H values in the alpine
      compared to the temperate grassland. More importantly, inflorescences had
      typically much higher n-alkane concentrations than other organs while roots had
      very low n-alkane concentrations. Most interestingly, the delta(2)H values of the
      carbon autonomous plant organs leaves, sheaths and stems were in general depleted
      compared to the overall mean delta(2)H value of a species, while non-carbon
      autonomous organs such as roots and inflorescences show delta(2)H values that are
      higher compared to the overall mean delta(2)H value of a species. We attribute
      organ-specific delta(2)H values to differences in the H-NADPH biosynthetic origin
      in different plant organs as a function of their carbon relationships. Finally,
      we employed simple mass balance calculations to show that leaves are in fact the
      main source of n-alkanes in the sediment. As such, studies assessing the
      environmental and physiological drivers of n-alkanes that focus on leaves produce
      relationships that can be employed to interpret the delta(2)H values of n-alkanes
      derived from sediments. This is despite the significant differences that we found
      among the delta(2)H values in the different plant organs. Our study brings new
      insights into the natural variability of n-alkane delta(2)H values and has
      implications for the interpretation of n-alkane delta(2)H values in ecological
      and paleohydrological research. 

PMID- 25761444
TI  - Autumn leaf subsidies influence spring dynamics of freshwater plankton
      communities.
AB  - While ecologists primarily focus on the immediate impact of ecological subsidies,
      understanding the importance of ecological subsidies requires quantifying the
      long-term temporal dynamics of subsidies on recipient ecosystems. Deciduous leaf
      litter transferred from terrestrial to aquatic ecosystems exerts both immediate
      and lasting effects on stream food webs. Recently, deciduous leaf additions have
      also been shown to be important subsidies for planktonic food webs in ponds
      during autumn; however, the inter-seasonal effects of autumn leaf subsidies on
      planktonic food webs have not been studied. We hypothesized that autumn leaf drop
      will affect the spring dynamics of freshwater pond food webs by altering the
      availability of resources, water transparency, and the metabolic state of ponds.
      We created leaf-added and no-leaf-added field mesocosms in autumn 2012, allowed
      mesocosms to ice-over for the winter, and began sampling the physical, chemical,
      and biological properties of mesocosms immediately following ice-off in spring
      2013. At ice-off, leaf additions reduced dissolved oxygen, elevated total
      phosphorus concentrations and dissolved materials, and did not alter temperature
      or total nitrogen. These initial abiotic effects contributed to higher bacterial
      densities and lower chlorophyll concentrations, but by the end of spring, the
      abiotic environment, chlorophyll and bacterial densities converged. By contrast,
      zooplankton densities diverged between treatments during the spring, with leaf
      additions stimulating copepods but inhibiting cladocerans. We hypothesized that
      these differences between zooplankton orders resulted from resource shifts
      following leaf additions. These results suggest that leaf subsidies can alter
      both the short- and long-term dynamics of planktonic food webs, and highlight the
      importance of fully understanding how ecological subsidies are integrated into
      recipient food webs. 

PMID- 25761445
TI  - Phase shift facilitation following cyclone disturbance on coral reefs.
AB  - While positive interactions have been observed to influence patterns of
      recruitment and succession in marine and terrestrial plant communities, the role
      of facilitation in macroalgal phase shifts is relatively unknown. In December
      2012, typhoon Bopha caused catastrophic losses of corals on the eastern reefs of
      Palau. Within weeks of the typhoon, an ephemeral bloom of monospecific macroalgae
      (Liagora sp.) was observed, reaching a peak of 38.6% cover in February 2013. At
      this peak, we observed a proliferation of a second macroalgal species, Lobophora
      variegata. Lobophora was distributed non-randomly, with higher abundances
      occurring within the shelter of Liagora canopies than on exposed substrates. Bite
      rates of two common herbivorous fish (Chlorurus sordidus and Ctenochaetus
      striatus) were significantly higher outside canopies (2.5- and sixfold,
      respectively), and cage exclusion resulted in a significant increase in Lobophora
      cover. Experimental removal of Liagora canopies resulted in a 53.1% decline in
      the surface area of Lobophora after 12 days, compared to a 51.7% increase within
      canopies. Collectively, these results indicate that Liagora canopies act as
      ecological facilitators, providing a 'nursery' exclusion zone from the impact of
      herbivorous fish, allowing for the establishment of understory Lobophora. While
      the ephemeral Liagora bloom had disappeared entirely 9 months post-typhoon, the
      facilitated shift to Lobophora has persisted for over 18 months, dominating ~40%
      of the reef substrate. While acute disturbance events such as typhoons have been
      suggested as a mechanism to reverse algal phase shifts, our results suggest that
      typhoons may also trigger, rather than just reverse, phase shifts.

PMID- 25761446
TI  - Does extreme environmental severity promote plant facilitation? An experimental
      field test in a subtropical coastal dune.
AB  - The stress gradient hypothesis (SGH) postulates how the balance between plant
      competition and facilitation shifts along environmental gradients. Early
      formulations of the SGH predicted that facilitation should increase monotonically
      with stress. However, a recent theoretical refinement of the SGH postulates
      stronger facilitation under moderate stress, followed by a decreasing role of
      facilitation in the most severe environments. We conducted field experiments
      along the most severe part of a coastal dune gradient in southeast Brazil to test
      the effect of stress on the intensity and importance of the net interactions
      between two tree species. First, we compared the performance of distinct life
      stages of Ternstroemia brasiliensis in the presence and absence of Guapira
      opposita adults along a beach-to-inland gradient, a gradient of environmental
      severity. To test the effect of one stress factor in particular, we also
      manipulated water availability, a limiting resource due to the sandy soils. At
      the most severe part of the coastal gradient (i.e. closest to the seashore), both
      intensity and importance of the interaction between G. opposita and T.
      brasiliensis were negatively related to stress, with a pattern consistent across
      distinct life stages of the target species. However, the sign of the net
      interaction depended on the life stage of the target species. Our results provide
      empirical evidence that the role of facilitation tends to wane, leading to
      neutral or even negative net interactions between species as stress reaches its
      maximum, as predicted by the recent refinements of the SGH. 

PMID- 25761447
TI  - Is the positive relationship between species richness and shoot morphological
      plasticity mediated by ramet density or is there a direct link?
AB  - Little is known about the consequences of phenotypic plasticity in co-existing
      species for plant community structure. However, it has been proposed that the
      potential of plants to exhibit plastic responses to light availability could be a
      key factor determining the capability of individuals to co-exist at small scales.
      Our previous research demonstrated that morphological plasticity to light was
      positively related to small-scale species richness in a temperate grassland.
      However, it remained unclear whether this relationship was solely due to a higher
      shoot density in plastic assemblages, or whether diversity was directly related
      to the morphological plasticity of the co-inhabitants. We used two data sets to
      clarify this relationship: experimentally acquired estimates of plasticity to
      light availability for 45 herbaceous plant species, and species richness and
      ramet density data from a 2-year permanent plot study in a semi-natural
      calcareous grassland. There was little ramet mortality observed in the permanent
      plot study indicating that the link between plasticity and richness does not
      operate through reduced mortality in more morphologically plastic assemblages.
      The local density of ramets explained most of variation in small-scale richness,
      but there was also a significant direct density-independent effect of mean shoot
      plasticity on richness, showing that plasticity to light directly enhances the
      small-scale co-existence of species. 

PMID- 25761448
TI  - Super adsorption capability from amorphousization of metal oxide nanoparticles
      for dye removal.
AB  - Transitional metal oxide nanoparticles as advanced environment and energy
      materials require very well absorption performance to apply in practice. Although
      most metal oxides are based on crystalline, high activities can also be achieved
      with amorphous phases. Here, we reported the adsorption behavior and mechanism of
      methyl blue (MB) on the amorphous transitional metal oxide (Fe, Co and Ni oxides)
      nanoparticles, and we demonstrated that the amorphousization of transitional
      metal oxide (Fe, Co and Ni oxides) nanoparticles driven by a novel process
      involving laser irradiation in liquid can create a super adsorption capability
      for MB, and the maximum adsorption capacity of the fabricated NiO amorphous
      nanostructure reaches up to 10584.6 mgg(-1), the largest value reported to date
      for all MB adsorbents. The proof-of-principle investigation of NiO amorphous
      nanophase demonstrated the broad applicability of this methodology for obtaining
      new super dyes adsorbents. 

PMID- 25761449
TI  - A novel procedure combining transoral resection and set-back tongue flap for
      oropharyngeal cancer.
AB  - Seven patients with advanced lateral oropharyngeal cancer (T3N2bM0, or T4N2bM0)
      underwent transoral lateral oropharyngectomy (TLO) with reconstruction performed
      through set-back tongue flap and polyglycolic acid (PGA) sheet. TLO was performed
      following en bloc resection of tumors using endoscopy. To cover the resulting
      defect in the lateral oropharyngeal wall, the set-back tongue flap was moved
      posteriorly and laterally to the area of the tongue base and lateral pharyngeal
      wall. The tip of the set-back tongue flap was sutured to the lateral pharynx to
      reconstruct the elevated tongue base and altered anterior pillar. The defect on
      the floor of the mouth was reconstructed using a PGA sheet. Following surgery,
      the mean observation period was 24 months. The mean operating time was 4 h and 2
      min, with an average blood loss of 68.1 ml. All oral intake resumed on the first
      postoperative day via gastric tube. The mean gastric tube removal time was 1.6
      postoperative days as a result of sufficient oral intake. None of the patients
      received postoperative radiotherapy or displayed evidence of tumor recurrence. We
      conclude that this novel procedure is highly effective for treating advanced
      oropharyngeal cancer as it demonstrates good prognostic and functional outcomes.

PMID- 25761450
TI  - Hematopoietic Stem Cell Gene Therapy Corrects Neuropathic Phenotype in Murine
      Model of Mucopolysaccharidosis Type II.
AB  - Mucopolysaccharidosis type II (MPS II) is a neuropathic lysosomal storage
      disorder caused by a deficiency of iduronate-2-sulfatase (IDS), which leads to
      the accumulation of glycosaminoglycans (GAGs). We demonstrated that biochemical
      alterations in the brains of MPS II mice are not corrected by bone marrow
      transplantation (BMT) or enzyme replacement therapy, although BMT has been shown
      to be effective for other neurodegenerative MPSs, such as Hurler syndrome. In
      this study, we demonstrated that lentiviral isogeneic hematopoietic stem cell
      (HSC) gene therapy corrected neuronal manifestations by ameliorating lysosomal
      storage and autophagic dysfunction in the brains of MPS II mice. IDS-transduced
      HSCs increased enzyme activity both in various visceral organs and the CNS.
      Decreased levels of GAGs were observed in many organs, including cerebra, after
      transplantation of IDS-transduced HSCs. In addition, lentiviral HSC gene therapy
      normalized the secondary accumulation of autophagic substrates, such as p62 and
      ubiquitin-protein conjugates, in cerebra. Furthermore, in contrast to naive MPS
      II mice, there was no deterioration of neuronal function observed in transplant
      recipients. These results indicated that lentiviral HSC gene therapy is a
      promising approach for the treatment of CNS lesions in MPS II. 

PMID- 25761451
TI  - The Lay Health Educator Program: Evaluating the Impact of this Community Health
      Initiative on the Medical Education of Resident Physicians.
AB  - Resident physicians receive little training designed to help them develop an
      understanding of the health literacy and health concerns of laypersons. The
      purpose of this study was to assess whether residents improve their understanding
      of health concerns of community members after participating in the Lay Health
      Educator Program, a health education program provided through a medical-religious
      community partnership. The impact was evaluated via pre-post surveys and open
      ended responses. There was a statistically significant change in the residents'
      (n = 15) understanding of what the public values as important with respect to
      specific healthcare topics. Findings suggest participation in a brief, formal
      community engagement activity improved medical residents' confidence with
      community health education. 

PMID- 25761452
TI  - Metallic nickel nitride nanosheets realizing enhanced electrochemical water
      oxidation.
AB  - Exploring efficient and inexpensive oxygen evolution reaction (OER)
      electrocatalysts is of great importance for various electrochemical energy
      storage and conversion technologies. Ni-based electrocatalysts have been actively
      pursued because of their promising activity and earth abundance. However, the OER
      efficiency for most of the developed Ni-based electrocatalysts has been
      intrinsically limited due to their low electrical conductivity and poor active
      site exposure yield. Herein, we report metallic Ni3N nanosheets as an efficient
      OER electrocatalyst for the first time. The first-principles calculations and
      electrical transport property measurements unravel that the Ni3N is intrinsically
      metallic, and the carrier concentration can be remarkably improved with
      dimensional confinement. The EXAFS spectra provide solid evidence that the Ni3N
      nanosheets have disordered structure resultant of dimensional reduction, which
      then could provide more active sites for OER. Benefiting from enhanced electrical
      conductivity with metallic behavior and atomically disordered structure, the Ni3N
      nanosheets realize intrinsically improved OER activity compared with bulk Ni3N
      and NiO nanosheets. Our finding suggests that metallic nitride nanosheets could
      serve as a new group of OER electrocatalysts with excellent property. 

PMID- 25761453
TI  - "Dual role" guiding catheter: a new technique for patients requiring coronary
      protection during transcatheter aortic valve implantation.
AB  - Coronary occlusion is a life-threatening complication during transcatheter aortic
      valve implantation (TAVI) that requires immediate revascularization.
      Conventionally, a total of 3 catheters are required to protect the coronary ostia
      during TAVI: a pigtail catheter for the angiographic evaluation of valve
      positioning, a guiding catheter, and a TAVI delivery system. In this case series,
      we present a new, simplified technique for patients who require coronary
      protection during TAVI using a total of only 2 catheters: a guiding catheter and
      TAVI delivery system. This simplified technique results in a simpler procedure
      and reduces vascular complications in this high-risk cohort. 

PMID- 25761454
TI  - Measuring cognitive load during simulation-based psychomotor skills training:
      sensitivity of secondary-task performance and subjective ratings.
AB  - As interest in applying cognitive load theory (CLT) to the study and design of
      pedagogic and technological approaches in healthcare simulation grows, suitable
      measures of cognitive load (CL) are needed. Here, we report a two-phased study
      investigating the sensitivity of subjective ratings of mental effort (SRME) and
      secondary-task performance (signal detection rate, SDR and recognition reaction
      time, RRT) as measures of CL. In phase 1 of the study, novice learners and expert
      surgeons attempted a visual-monitoring task under two conditions: single-task
      (monitoring a virtual patient's heart-rate) and dual-task (tying surgical knots
      on a bench-top simulator while monitoring the virtual patient's heart-rate).
      Novices demonstrated higher mental effort and inferior secondary-task performance
      on the dual-task compared to experts (RRT 1.76 vs. 0.73, p = 0.012; SDR 0.27 vs.
      0.97, p < 0.001; SRME 7.75 vs. 2.80, p < 0.001). Similarly, secondary task
      performance deteriorated from baseline to dual-task among novices (RRT 0.63 vs.
      1.76 s, p < 0.006 and SDR 1.00 vs. 0.27, p < 0.001), but not experts (RRT 0.63
      vs. 0.73 s, p = 0.124 and SDR 1.00 vs. 0.97, p = 0.178). In phase 2, novices
      practiced surgical knot-tying on the bench top simulator during consecutive dual
      task trials. A significant increase in SDR (F(9,63) = 6.63, p < 0.001, f = 0.97)
      and decrease in SRME (F(9,63) = 9.39, p < 0.001, f = 1.04) was observed during
      simulation training, while RRT did not change significantly (F(9,63) = 1.18, p <
      0.32, f = 0.41). The results suggest subjective ratings and dual-task performance
      can be used to track changes in CL among novices, particularly in early phases of
      simulation-based skills training. The implications for measuring CL in simulation
      instructional design research are discussed. 

PMID- 25761455
TI  - Three-layered radio frequency coil arrangement for sodium MRI of the human brain
      at 9.4 Tesla.
AB  - PURPOSE: A multinuclei imaging setup with the capability to acquire both sodium
      ((23) Na) and proton ((1) H) signals at 9.4 Tesla is presented. The main
      objective was to optimize coil performance at the (23) Na frequency while still
      having the ability to acquire satisfactory (1) H images. METHODS: The setup
      consisted of a combination of three radio frequency (RF) coils arranged in three
      layers: the innermost layer was a 27-channel (23) Na receive helmet which was
      surrounded by a four-channel (23) Na transceiver array. The outer layer consisted
      of a four-channel (1) H dipole array for B0 shimming and anatomical localization.
      Transmit and receive performance of the (23) Na arrays was compared to a single
      tuned (23) Na birdcage resonator. RESULTS: While the transmit efficiency of the
      (23) Na transceiver array was comparable to the birdcage, the (23) Na receive
      array provided substantial signal-to-noise ratio (SNR) gain near the surface and
      comparable SNR in the center. The utility of this customized setup was
      demonstrated by (23) Na images of excellent quality. CONCLUSION: High SNR,
      efficient transmit excitation and B0 shimming capability can be achieved for (23)
      Na MRI at 9.4T using novel coil combination. This RF configuration is easily
      adaptable to other multinuclei applications at ultra high field (>= 7T).

PMID- 25761456
TI  - Pharmacokinetically based dosing of weekly paclitaxel to reduce drug-related
      neurotoxicity based on a single sample strategy.
AB  - PURPOSE: The present simulation study was initiated to develop a limited sampling
      strategy and pharmacokinetically based dosing algorithm of weekly paclitaxel
      based on pharmacokinetic (PK) and chemotherapy-induced peripheral neuropathy
      (CIPN) data from a large database. METHODS: We used paclitaxel plasma
      concentrations from 200 patients with solid tumors receiving weekly paclitaxel
      infusions to build a population PK model and a proportional odds model on CIPN.
      Different limited sampling strategies were tested on their accuracy to estimate
      the individual paclitaxel time-above-threshold-concentration of 0.05 umol/L (T
      c>0.05uM), which is a common threshold for paclitaxel. A dosing algorithm was
      developed based on the population distribution of paclitaxel T c>0.05uM and the
      correlation between paclitaxel T c>0.05uM and CIPN. A trial simulation based on
      paclitaxel PK and CIPN was performed using empirical Bayes estimations, applying
      the proposed dosing algorithm and a single 24-h paclitaxel PK sample. RESULTS: A
      single paclitaxel plasma concentration taken 18-30 h after the start of
      chemotherapy infusion adequately predicted T c>0.05uM. By using an empirical
      dosing algorithm to target an average paclitaxel T c>0.05uM between 10 and 14 h,
      Bayesian simulations of repetitive (adapted) dosing suggested a potential
      reduction of grade 2 CIPN from 9.6 to 4.4 %. CONCLUSIONS: This simulation study
      proposes a pharmacokinetically based dosing algorithm for weekly paclitaxel and
      shows potential improvement of the benefit/risk ratio by using empirical Bayesian
      models.

PMID- 25761457
TI  - Tropical cyclone rainfall area controlled by relative sea surface temperature.
AB  - Tropical cyclone rainfall rates have been projected to increase in a warmer
      climate. The area coverage of tropical cyclones influences their impact on human
      lives, yet little is known about how tropical cyclone rainfall area will change
      in the future. Here, using satellite data and global atmospheric model
      simulations, we show that tropical cyclone rainfall area is controlled primarily
      by its environmental sea surface temperature (SST) relative to the tropical mean
      SST (that is, the relative SST), while rainfall rate increases with increasing
      absolute SST. Our result is consistent with previous numerical simulations that
      indicated tight relationships between tropical cyclone size and mid-tropospheric
      relative humidity. Global statistics of tropical cyclone rainfall area are not
      expected to change markedly under a warmer climate provided that SST change is
      relatively uniform, implying that increases in total rainfall will be confined to
      similar size domains with higher rainfall rates. 

PMID- 25761458
TI  - Recent Developments in Pharmacotherapy of Alcoholism.
AB  - INTRODUCTION: Alcohol use disorders are common, but only a small minority of
      patients receive adequate treatment. Cognitive-behavioural therapies,
      motivational enhancement interviewing and brief interventions are established
      treatments, but few pharmacotherapies are available. AREAS COVERED: This
      narrative focuses on the neurobiological basis of alcohol use disorders and on
      emerging drugs that either have recently been approved or look likely to find
      their way into clinical practice. To date, acamprosate and the opioid antagonist
      naltrexone have been approved for treatment of alcohol dependence. Recently, the
      mu-opioid antagonist and partial kappa agonist nalmefene was approved by the
      European Medicines Agency for reduction of alcohol consumption. Novel clinical
      approaches include drugs established for other indications such as the GABA-B
      receptor agonist baclofen, anticonvulsants such as topiramate and gabapentin, the
      partial nicotine receptor agonist varenicline, and other drugs. Developments in
      pharmacogenetics are discussed. CONCLUSIONS: The development of pharmaceutical
      agents to treat alcohol use disorders has lagged behind that of depression and
      schizophrenic psychosis and is hampered by an incomplete understanding of the
      neurobiological background. Pharmacogenetics may improve treatment in the future.

PMID- 25761459
TI  - Immunogenicity and efficacy of flagellin-envelope fusion dengue vaccines in mice
      and monkeys.
AB  - The envelope (E) protein of flaviviruses includes three domains, EI, EII, and
      EIII, and is the major protective antigen. Because EIII is rich in type-specific
      and subcomplex-specific neutralizing epitopes and is easy to express, it is
      particularly attractive as a recombinant vaccine antigen. VaxInnate has developed
      a vaccine platform that genetically links vaccine antigens to bacterial
      flagellin, a Toll-like receptor 5 ligand. Here we report that tetravalent dengue
      vaccines (TDVs) consisting of four constructs, each containing two copies of EIII
      fused to flagellin (R3.2x format), elicited robust and long-lived neutralizing
      antibodies (geometric mean titers of 200 to 3,000), as measured with a 50% focus
      reduction neutralization test (FRNT50). In an immunogenicity study, rhesus
      macaques (n = 2) immunized subcutaneously with 10 MUg or 90 MUg of TDV three or
      four times, at 4- to 6-week intervals, developed neutralizing antibodies to four
      dengue virus (DENV) serotypes (mean post-dose 3 FRNT50 titers of 102 to 601). In
      an efficacy study, rhesus macaques (n = 4) were immunized intramuscularly with 16
      MUg or 48 MUg of TDV or a placebo control three times, at 1-month intervals. The
      animals that received 48-MUg doses of TDV developed neutralizing antibodies
      against the four serotypes (geometric mean titers of 49 to 258) and exhibited
      reduced viremia after DENV-2 challenge, with a group mean viremia duration of
      1.25 days and 2 of 4 animals being completely protected, compared to the placebo
      treated animals, which all developed viremia, with a mean duration of 4 days. In
      conclusion, flagellin-EIII fusion vaccines are immunogenic and partially
      protective in a nonhuman primate model. 

PMID- 25761460
TI  - Cross-Sectional Analysis of Selected Genital Tract Immunological Markers and
      Molecular Vaginal Microbiota in Sub-Saharan African Women, with Relevance to HIV
      Risk and Prevention.
AB  - Data on immune mediators in the genital tract and the factors that modulate them
      in sub-Saharan women are limited. Cervicovaginal lavage (CVL) samples from 430
      sexually active women from Kenya, South Africa, and Rwanda were analyzed for 12
      soluble immune mediators using Bio-Plex and Meso Scale Discovery multiplex
      platforms, as well as single enzyme-linked immunosorbent assays. Ten bacterial
      species were quantified in vaginal swab samples. Bacterial vaginosis (BV) was
      defined by Nugent scoring. CVL samples from HIV-infected women showed a clear-cut
      proinflammatory profile. Pregnant women, adolescents, and women engaging in
      traditional vaginal practices differed in specific soluble markers compared to
      reference groups of adult HIV-negative women. Cervical mucus, cervical ectopy,
      abnormal vaginal discharge, and having multiple sex partners were each associated
      with an increase in inflammatory mediators. The levels of interleukin-1alpha (IL
      1alpha), IL-1beta, IL-6, IL-12(p70), and IL-8 were elevated, whereas the IL
      1RA/IL-1(alpha+beta) ratio decreased in women with BV. The level of gamma
      interferon-induced protein 10 was lower in BV-positive than in BV-negative women,
      suggesting its suppression as a potential immune evasion mechanism by BV
      associated bacteria. Lactobacillus crispatus and Lactobacillus vaginalis were
      associated with decreased proinflammatory cytokines and each BV-associated
      species with increased proinflammatory cytokines. Remarkably, the in vitro anti
      HIV activity of CVL samples from BV-positive women was stronger than that of BV
      negative women. In conclusion, we found significant associations of factors,
      including vaginal microbiota, which can influence immune mediators in the vaginal
      environment in sexually active women. These factors need to be considered when
      establishing normative levels or pathogenic cutoffs of biomarkers of inflammation
      and associated risks in African women. 

PMID- 25761462
TI  - Mean platelet volume needs standardisation. Comment on Asher et al. Thromb
      Haemost 2014; 112: 137-141.

PMID- 25761463
TI  - Anomalously augmented charge transport capabilities of biomimetically transformed
      collagen intercalated nanographene-based biocolloids.
AB  - Collagen microfibrils biomimetically intercalate graphitic structures in aqueous
      media to form graphene nanoplatelet-collagen complexes (G-Cl). Synthesized G-Cl
      based stable, aqueous bionanocolloids exhibit anomalously augmented charge
      transportation capabilities oversimple collagen or graphene based colloids. The
      concentration tunable electrical transport properties of synthesized aqueous G-Cl
      bionanocolloids has been experimentally observed, theoretically analyzed, and
      mathematically modeled. A comprehensive approach to mathematically predict the
      electrical transport properties of simple graphene and collagen based colloids
      has been presented. A theoretical formulation to explain the augmented transport
      characteristics of the G-Cl bionanocolloids based on the physicochemical
      interactions among the two entities, as revealed from extensive characterizations
      of the G-Cl biocomplex, has also been proposed. Physical interactions between the
      zwitterionic amino acid molecules within the collagen triple helix with the polar
      water molecules and the delocalized pi electrons of graphene and subsequent
      formation of partially charged entities has been found to be the crux mechanism
      behind the augmented transport phenomena. The analysis has been observed to
      accurately predict the degree of enhancement in transport of the concentration
      tunable composite colloids over the base colloids. The electrically active G-Cl
      bionanocolloids with concentration tunability promises find dual utility in novel
      gel bioelectrophoresis-based protein separation techniques and advanced surface
      charge modulated drug delivery using biocolloids. 

PMID- 25761461
TI  - Defining species-specific immunodominant B cell epitopes for molecular serology
      of Chlamydia species.
AB  - Urgently needed species-specific enzyme-linked immunosorbent assays (ELISAs) for
      the detection of antibodies against Chlamydia spp. have been elusive due to high
      cross-reactivity of chlamydial antigens. To identify Chlamydia species-specific B
      cell epitopes for such assays, we ranked the potential epitopes of immunodominant
      chlamydial proteins that are polymorphic among all Chlamydia species. High
      scoring peptides were synthesized with N-terminal biotin, followed by a serine
      glycine-serine-glycine spacer, immobilized onto streptavidin-coated microtiter
      plates, and tested with mono-specific mouse hyperimmune sera against each
      Chlamydia species in chemiluminescent ELISAs. For each of nine Chlamydia species,
      three to nine dominant polymorphic B cell epitope regions were identified on
      OmpA, CT618, PmpD, IncA, CT529, CT442, IncG, Omp2, TarP, and IncE proteins.
      Peptides corresponding to 16- to 40-amino-acid species-specific sequences of
      these epitopes reacted highly and with absolute specificity with homologous, but
      not heterologous, Chlamydia monospecies-specific sera. Host-independent
      reactivity of such epitopes was confirmed by testing of six C. pecorum-specific
      peptides from five proteins with C. pecorum-reactive sera from cattle, the
      natural host of C. pecorum. The probability of cross-reactivity of peptide
      antigens from closely related chlamydial species or strains correlated with
      percent sequence identity and declined to zero at <50% sequence identity. Thus,
      phylograms of B cell epitope regions predict the specificity of peptide antigens
      for rational use in the genus-, species-, or serovar-specific molecular serology
      of Chlamydia spp. We anticipate that these peptide antigens will improve
      chlamydial serology by providing easily accessible assays to nonspecialist
      laboratories. Our approach also lends itself to the identification of relevant
      epitopes of other microbial pathogens. 

PMID- 25761464
TI  - Alginate/nanohydroxyapatite scaffolds with designed core/shell structures
      fabricated by 3D plotting and in situ mineralization for bone tissue engineering.
AB  - Composite scaffolds, especially polymer/hydroxyapatite (HAP) composite scaffolds
      with predesigned structures, are promising materials for bone tissue engineering.
      Various methods including direct mixing of HAP powder with polymers or incubating
      polymer scaffolds in simulated body fluid for preparing polymer/HAP composite
      scaffolds are either uncontrolled or require long times of incubation. In this
      work, alginate/nano-HAP composite scaffolds with designed pore parameters and
      core/shell structures were fabricated using 3D plotting technique and in situ
      mineralization under mild conditions (at room temperature and without the use of
      any organic solvents). Light microscopy, scanning electron microscopy,
      microcomputer tomography, X-ray diffraction, and Fourier transform infrared
      spectroscopy were applied to characterize the fabricated scaffolds. Mechanical
      properties and protein delivery of the scaffolds were evaluated, as well as the
      cell response to the scaffolds by culturing human bone-marrow-derived mesenchymal
      stem cells (hBMSC). The obtained data indicate that this method is suitable to
      fabricate alginate/nano-HAP composite scaffolds with a layer of nano-HAP, coating
      the surface of the alginate strands homogeneously and completely. The surface
      mineralization enhanced the mechanical properties and improved the cell
      attachment and spreading, as well as supported sustaining protein release,
      compared to pure alginate scaffolds without nano-HAP shell layer. The results
      demonstrated that the method provides an interesting option for bone tissue
      engineering application. 

PMID- 25761465
TI  - Selective (bio)functionalization of solid-state nanopores.
AB  - We present a method to selectively (bio)functionalize nanoscale features with the
      same materials chemistry. It was successfully combined with nanosphere
      lithography to fabricate and functionalize solid-state nanopores with PEG
      brushes, supported lipid membranes, and functional proteins over large areas. The
      method is inexpensive, can be performed without specialized equipment, and can be
      applied to both topographic and planar surface modification. 

PMID- 25761466
TI  - Concomitant leptospirosis-hantavirus co-infection in acute patients hospitalized
      in Sri Lanka: implications for a potentially worldwide underestimated problem -
      ERRATUM.

PMID- 25761467
TI  - A cost-effectiveness analysis of teledietetics in short-, intermediate-, and long
      term weight reduction.
AB  - INTRODUCTION: To evaluate the effectiveness of teledietetics in weight loss for
      24 weeks and the cost-effectiveness of weight loss between face-to-face and
      teledietetics services. METHODS: The study was conducted at a community health
      center and a community dietetics clinic. The study was a quasiexperimental
      design. Fifty adults aged 20-50 with a BMI >=23 participated in the study. The
      face-to-face (FD) group received 12 dietary counselling sessions and recorded
      their diet in a log book. The teledietetics (TD) group attended three group
      nutrition seminars and recorded their diet on a Web-based platform. Changes in
      variables were compared using an independent t-test. Direct and indirect costs
      were applied to compute cost-effectiveness ratios. RESULTS: At week 6, the FD
      group showed greater reductions in all variables than did the TD group. At week
      12, the effects reversed. At week 24, the accumulated reductions in weight and
      fat in the TD group were significantly higher than those in the FD group (all at
      p < 0.0001). The observed direct costs for 1% weight loss and 1% fat loss were
      USD 28.24 and USD17.09, respectively. DISCUSSION: A dietetic service delivered as
      a teledietetics model is more cost-effective than the face-to-face dietetics
      model in weight reduction.

PMID- 25761468
TI  - Safety of clinical and non-clinical decision makers in telephone triage: a
      narrative review.
AB  - Patient safety is a persistent problem in telephone triage research; however,
      studies have not differentiated between clinicians' and non-clinicians'
      respective safety. Currently, four groups of decision makers perform aspects of
      telephone triage: clinicians (physicians, nurses), and non-clinicians (emergency
      medical dispatchers (EMD) and clerical staff). Using studies published between
      2002-2012, we applied Donabedian's structure-process-outcome model to examine
      groups' systems for evidence of system completeness (a minimum measure of
      structure and quality). We defined system completeness as the presence of a
      decision maker and four additional components: guidelines, documentation,
      training, and standards. Defining safety as appropriate referrals (AR) - (right
      time, right place with the right person), we measured each groups' corresponding
      AR rate percentages (outcomes). We analyzed each group's respective decision
      making process as a safe match to the telephone triage task, based on each
      group's system structure completeness, process and AR rates (outcome). Studies
      uniformly noted system component presence: nurses (2-4), physicians (1), EMDs
      (2), clerical staff (1). Nurses had the highest average appropriate referral (AR)
      rates (91%), physicians' AR (82% average). Clerical staff had no system and did
      not perform telephone triage by standard definitions; EMDs may represent the use
      of the wrong system. Telephone triage appears least safe after hours when
      decision makers with the least complete systems (physicians, clerical staff)
      typically manage calls. At minimum, telephone triage decision makers should be
      clinicians; however, clinicians' safety calls for improvement. With improved
      training, standards and CDSS quality, the 24/7 clinical call center has potential
      to represent the national standard. 

PMID- 25761470
TI  - Internet-based questionnaire to self-assess autonomy and obtain a life-at-home
      services enforcement plan: a retrospective validation study.
AB  - BACKGROUND: In France, a specially-designed care plan for the elderly is
      generally based on an interdisciplinary, complex and time-consuming process. The
      health system assigns care throughout the social and health care services using
      multiple providers and sites. OBJECTIVE: The free website www.jesuisautonome.fr
      offers senior citizens and their families an opportunity to assess their own
      independence at home using a questionnaire in order to obtain a personal, life-at
      home, enforcement plan. We aim to examine the correlation between the specially
      designed care plan obtained by the usual assessment method and through self
      evaluation via the website. METHODS: Community-dwelling subjects, consulting for
      the first time from December 2012 to July 2014, were under consideration.
      Patients were assessed using the Comprehensive Geriatric Assessment (CGA) and
      also independently during the first consultation; patients and their caregivers
      were then asked to fill out the questionnaire on the website. The two methods
      were compared using the Bland-Altman analysis for quantitative values and Kappa
      values for qualitative values. RESULTS: 73 patients completed the study.
      Correlation was excellent between parameters that did not include error due to
      risk to the patient (assistance with bathing and dressing, a nurse for drug
      distribution, measure of legal protection). Correlation was good with housekeeper
      hours that involved a financial cost to state social services and families. The
      GIR (Iso Ressource Groupe), which in France serves as a reference to determine
      social disability of the elderly, was similar. CONCLUSION: Our study confirms the
      potential of the website www.jesuisautonome.fr. to improve the delivery of health
      and social care services.

PMID- 25761469
TI  - A cohort study following up on a randomised controlled trial of a telemedicine
      application in COPD patients.
AB  - INTRODUCTION: The studies that constitute the knowledge base of evidence based
      medicine represent only 5%-50% of patients seen in routine clinical practice.
      Therefore, whether the available evidence applies to the implementation of a
      particular service often remains unclear. Chronic obstructive pulmonary disease
      (COPD) is no exception. METHODS: In this article, the effects of implementing a
      telemedicine intervention for COPD patients were analysed using data collected
      before, during, and after a randomised controlled trial (RCT).More specifically,
      regression techniques using robust variance estimators were used to analyse
      whether the use of telemedicine, patient age, and gender could explain the risk
      of readmission, length of hospital admission, and death during a five-year
      observation period. RESULTS: Increased risk of readmission was significantly
      related to both use of telemedicine and increased age in three sub-periods of the
      study, whereas women showed a more pronounced risk of readmission than men only
      during and after the RCT period. The number of days admitted to hospital was
      higher for patients using telemedicine and being of older age. Risk of death
      during the observation period was decreased for patients using telemedicine and
      for female patients and increased for elderly patients. No interaction between
      intervention and time period was observed.Statistically significant relationships
      were identified between use of telemedicine and risk of readmission, days
      admitted to hospital, and death. DISCUSSION: Research on effect modification in
      telemedicine is essential in designing future implementation of interventions as
      it cannot be taken for granted that effectiveness follows from efficacy.

PMID- 25761471
TI  - Dietary calcium concentration and cereals differentially affect mineral balance
      and tight junction proteins expression in jejunum of weaned pigs.
AB  - Ca plays an essential role in bone development; however, little is known about
      its effect on intestinal gene expression in juvenile animals. In the present
      study, thirty-two weaned pigs (9.5 (SEM 0.11) kg) were assigned to four diets
      that differed in Ca concentration (adequate v. high) and cereal composition
      (wheat-barley v. maize) to assess the jejunal and colonic gene expression of
      nutrient transporters, tight junction proteins, cytokines and pathogen-associated
      molecular patterns, nutrient digestibility, Ca balance and serum acute-phase
      response. To estimate the impact of mucosal bacteria on colonic gene expression,
      Spearman's correlations between colonic gene expression and bacterial abundance
      were computed. Faecal Ca excretion indicated that more Ca was available along the
      intestinal tract of the pigs fed high Ca diets as compared to the pigs fed
      adequate Ca diets (P> 0.05). High Ca diets decreased jejunal zonula occludens 1
      (ZO1) and occludin (OCLN) expression, up-regulated jejunal expression of toll
      like receptor 2 (TLR2) and down-regulated colonic GLUT2 expression as compared to
      the adequate Ca diets (P< 0.05). Dietary cereal composition up-regulated jejunal
      TLR2 expression and interacted (P= 0.021) with dietary Ca on colonic IL1B
      expression; high Ca concentration up-regulated IL1B expression with wheat-barley
      diets and down-regulated it with maize diets. Spearman's correlations (r> 0.35;
      P< 0.05) indicated an association between operational taxonomic units assigned to
      the phyla Bacteroidetes, Firmicutes and Proteobacteria and bacterial metabolites
      and mucosal gene expression in the colon. The present results indicate that high
      Ca diets have the potential to modify the jejunal and colonic mucosal gene
      expression response which, in turn, interacts with the composition of the basal
      diet and mucosa-associated bacteria in weaned pigs.

PMID- 25761472
TI  - Medical Costs and Healthcare Utilization among Cancer Decedents in the Last Year
      of Life in 2009.
AB  - PURPOSE: The purpose of this study was to evaluate the cancer care cost during
      the last year of life of patients in Korea. MATERIALS AND METHODS: We studied the
      breakdown of spending on the components of cancer care. Cancer decedents in 2009
      were identified from the Korean Central Cancer Registry and linked with the
      Korean National Health Insurance Claims Database. The final number of patients
      included in the study was 70,558. RESULTS: In 2009, the average cancer care cost
      during the last year of life was US $15,720. Patients under age 20 spent US
      $53,890 while those 70 or over spent US $11,801. Those with leukemia incurred the
      highest costs (US $43,219) while bladder cancer patients spent the least (US
      $13,155). General costs, drugs other than analgesics, and test fees were
      relatively high (29.7%, 23.8%, and 20.7% of total medical costs, respectively).
      Analgesic drugs, rehabilitation, and psychotherapy were still relatively low
      (4.3%, 0.7%, and 0.1%, respectively). Among the results of multiple regression
      analysis, few were notable. Age was found to be negatively related to cancer care
      costs while income level was positively associated. Those classified under
      distant Surveillance, Epidemiology, and End Results stages of cancer and higher
      comorbidity level also incurred higher cancer care costs. CONCLUSION: Average
      cancer care costs varied significantly by patient characteristics. However, the
      study results suggest an underutilization of support services likely due to lack
      of alternative accommodations for terminal cancer patients. Further examination
      of utilization patterns of healthcare resources will help provide tailored
      evidence for policymakers in efforts to reduce the burdens of cancer care.

PMID- 25761473
TI  - Interactome Analysis Reveals that Heterochromatin Protein 1gamma (HP1gamma) Is
      Associated with the DNA Damage Response Pathway.
AB  - PURPOSE: Heterochromatin protein 1gamma (HP1gamma) interacts with chromosomes by
      binding to lysine 9-methylated histone H3 or DNA/RNA. HP1gamma is involved in
      various biological processes. The purpose of this study is to gain an
      understanding of how HP1gamma functions in these processes by identifying
      HP1gamma-binding proteins using mass spectrometry. MATERIALS AND METHODS: We
      performed affinity purification of HP1gamma-binding proteins using G1/S phase or
      prometaphase HEK293T cell lysates that transiently express mock or FLAG-HP1gamma.
      Coomassie staining was performed for HP1gamma-binding complexes, using cell
      lysates prepared by affinity chromatography FLAG-agarose beads, and the bands
      were digested and then analyzed using a mass spectrometry. RESULTS: We identified
      99 HP1gamma-binding proteins with diverse cellular functions, including
      spliceosome, regulation of the actin cytoskeleton, tight junction, pathogenic
      Escherichia coli infection, mammalian target of rapamycin signaling pathway,
      nucleotide excision repair, DNA replication, homologous recombination, and
      mismatch repair. CONCLUSION: Our results suggested that HP1gamma is functionally
      active in DNA damage response via protein-protein interaction.

PMID- 25761474
TI  - Preliminary Suggestion about Staging of Anorectal Malignant Melanoma May Be Used
      to Predict Prognosis.
AB  - PURPOSE: Anorectal malignant melanomas (AMM) are rare and have poor survival. The
      study aims to evaluate the clinicopathologic characteristics and outcomes of
      patients with AMM, and to devise a staging system predictive of survival outcome.
      MATERIALS AND METHODS: This was a retrospective study of 28 patients diagnosed
      with, and treated for AMM. Patients classified by clinical staging of mucosal
      melanoma (MM) were reclassified via rectal and anal TNM staging. Survival
      outcomes were compared among patients grouped by the three different staging
      systems. RESULTS: The three staging systems were equated with similar figures for
      5-year overall survival (OS) and 5-year disease-free survival (DFS) of patients
      diagnosed with stage I disease. Patients (n=19) diagnosed with MM stage II
      disease were reclassified by rectal TNM staging into three subgroups: IIIA, IIIB,
      and IIIC. For these patients, both 5-year OS and 5-year DFS differed
      significantly between the subgroups IIIA and IIIC (OS: IIIA vs. IIIC, 66.7% vs.
      0%, p=0.002; DFS: IIIA vs. IIIC, 51.4% vs. 0%, p < 0.001). CONCLUSION: The
      accuracy of prognosis in patients diagnosed with AMM and lymph node metastasis
      has improved by using rectal TNM staging, which includes information regarding
      the number of lymph node metastases.

PMID- 25761475
TI  - Prediction of Lymph Node Metastasis by Tumor Dimension Versus Tumor Biological
      Properties in Head and Neck Squamous Cell Carcinomas.
AB  - PURPOSE: Lymph node metastasis (LNM) is a strong prognostic factor in many solid
      cancers, including head and neck squamous cell carcinomas (HNSCC), and LNM can be
      dependent upon primary tumor biology, as well as tumor dimension. Here, we
      investigate the relative risk of LNM in accordance to tumor dimension and biology
      in HNSCC subsites. MATERIALS AND METHODS: Medical data of 295 HNSCC patients who
      had undergone the initial curative surgery (oral tongue 174, oropharynx 75,
      hypopharynx 46) were analyzed to identify the significant predictive factor for
      LNM. Tumor volume and thickness were set as tumor dimensional variables, and
      biological variables included lymphovascular, perineural invasion, and tumor
      differentiation. Statistical analyses were conducted to assess the predictability
      of LNM from variables, and subgroup analyses according to the tumor subsites. In
      addition, we evaluated the impacts of tumor dimension and biological variables on
      the treatment outcomes and survival in HNSCC subsites. RESULTS: The overall tumor
      dimension and biological variables had a similar impact on the prediction of LNM
      in HNSCC (area under the curve, 0.7682 and 0.7717). The prediction sensitivity of
      LNM in oral tongue cancer was mainly dependent on tumor dimension, while LNM in
      oro- and hypo-pharynx cancers was more influenced by biological factors. Survival
      analyses also confirmed that biological factor was more powerful in estimating
      disease-free survival of hypopharyngeal cancer patients, while tumor dimension
      was more significant in that of oral cancer patients. CONCLUSION: Tumor dimension
      and biology have a significant, tumor subsite-dependent impact on the occurrence
      of LNM and disease-free survival in HNSCC.

PMID- 25761476
TI  - Systemic Inflammatory Response Markers and CA-125 Levels in Ovarian Clear Cell
      Carcinoma: A Two Center Cohort Study.
AB  - PURPOSE: We compared the predictive and prognostic values of leukocyte
      differential counts, systemic inflammatory (SIR) markers and cancer antigen 125
      (CA-125) levels, and identified the most useful marker in patients with ovarian
      clear cell carcinoma (OCCC). MATERIALS AND METHODS: The study included 109
      patients with OCCC who did not have any inflammatory conditions except
      endometriosis, and underwent primary debulking surgery between 1997 and 2012.
      Leukocyte differential counts (neutrophil, lymphocyte, monocyte, eosinophil,
      basophil, and platelet), SIR markers including neutrophil to lymphocyte ratio
      (NLR), monocyte to lymphocyte ratio (MLR), and platelet to lymphocyte ratio
      (PLR), and CA-125 levels were estimated to select potential markers for clinical
      outcomes. RESULTS: Among potential markers (neutrophil, monocyte, platelet, NLR,
      MLR, PLR, and CA-125 levels) selected by stepwise comparison, CA-125 levels were
      best at predicting advanced stage disease, suboptimal debulking and platinum
      resistance (cut-off values, >= 46.5, >= 11.45, and >= 66.4 U/mL; accuracies,
      69.4%, 78.7%, and 68.5%) while PLR >= 205.4 predicted non-complete response (CR;
      accuracy, 71.6%) most accurately. Moreover, PLR < 205.4 was an independent factor
      for the reduced risk of non-CR (adjusted odds ratio, 0.17; 95% confidence
      interval [CI], 0.04 to 0.69), and NLR < 2.8 was a favorable factor for improved
      progression-free survival (PFS; adjusted hazard ratio, 0.49; 95% CI, 0.25 to
      0.99) despite lack of a marker for overall survival among the potential markers.
      CONCLUSION: CA-125 levels may be the most useful marker for predicting advanced
      stage disease. Suboptimal debulking and platinum-resistance, and PLR and NLR may
      be most effective to predict non-CR and PFS in patients with OCCC.

PMID- 25761477
TI  - Carotid-Sparing TomoHelical 3-Dimensional Conformal Radiotherapy for Early
      Glottic Cancer.
AB  - PURPOSE: The purpose of this study was to investigate the dosimetric benefits and
      treatment efficiency of carotid-sparing TomoHelical 3-dimensional conformal
      radiotherapy (TH-3DCRT) for early glottic cancer. MATERIALS AND METHODS: Ten
      early-stage (T1N0M0) glottic squamous cell carcinoma patients were simulated,
      based on computed tomography scans. Two-field 3DCRT (2F-3DCRT), 3-field intensity
      modulated radiation therapy (3F-IMRT), TomoHelical-IMRT (TH-IMRT), and TH-3DCRT
      plans were generated with a 67.5-Gy total prescription dose to the planning
      target volume (PTV) for each patient. In order to evaluate the plan quality,
      dosimetric characteristics were compared in terms of conformity index (CI) and
      homogeneity index (HI) for PTV, dose to the carotid arteries, and maximum dose to
      the spinal cord. Treatment planning and delivery times were compared to evaluate
      treatment efficiency. RESULTS: The median CI was substantially better for the 3F
      IMRT (0.65), TH-IMRT (0.64), and TH-3DCRT (0.63) plans, compared to the 2F-3DCRT
      plan (0.32). PTV HI was slightly better for TH-3DCRT and TH-IMRT (1.05) compared
      to 2F-3DCRT (1.06) and 3F-IMRT (1.09). TH-3DCRT, 3F-IMRT, and TH-IMRT showed an
      excellent carotid sparing capability compared to 2F-3DCRT (p < 0.05). For all
      plans, the maximum dose to the spinal cord was < 45 Gy. The median treatment
      planning times for 2F-3DCRT (5.85 minutes) and TH-3DCRT (7.10 minutes) were much
      lower than those for 3F-IMRT (45.48 minutes) and TH-IMRT (35.30 minutes). The
      delivery times for 2F-3DCRT (2.06 minutes) and 3F-IMRT (2.48 minutes) were
      slightly lower than those for TH-IMRT (2.90 minutes) and TH-3DCRT (2.86 minutes).
      CONCLUSION: TH-3DCRT showed excellent carotid-sparing capability, while offering
      high efficiency and maintaining good PTV coverage.

PMID- 25761478
TI  - Is there a "Trial Effect" on Outcome of Patients with Metastatic Renal Cell
      Carcinoma Treated with Sunitinib?
AB  - PURPOSE: Studies suggested the existence of a 'trial effect', in which for a
      given treatment, participation in a clinical trial is associated with a better
      outcome. Sunitinib is a standard treatment for metastatic renal cell carcinoma
      (mRCC). We aimed to study the effect of clinical trial participation on the
      outcome of mRCC patients treated with sunitinib, which at present, is poorly
      defined. MATERIALS AND METHODS: The records of mRCC patients treated with
      sunitinib between 2004-2013 in 7 centers across 2 countries were reviewed. We
      compared the response rate (RR), progression free survival (PFS), and overall
      survival (OS), between clinical trial participants (n=49) and a matched cohort of
      non-participants (n=49) who received standard therapy. Each clinical trial
      participant was individually matched with a non-participant by clinicopathologic
      factors. PFS and OS were determined by Cox regression. RESULTS: The groups were
      matched by age (median 64), gender (male 67%), Heng risk (favorable 25%,
      intermediate 59%, poor 16%), prior nephrectomy (92%), RCC histology (clear cell
      86%), pre-treatment NLR (>3 in 55%, n=27), sunitinib induced hypertension (45%),
      and sunitinib dose reduction/treatment interruption (41%). In clinical trial
      participants versus non-participants, RR was partial response/stable disease 80%
      (n=39) versus 74% (n=36), and progressive disease 20% (n=10) versus 26% (n=13)
      (p=0.63, OR 1.2). The median PFS was 10 versus 11 months (HR=0.96, p=0.84), and
      the median OS 23 versus 24 months (HR=0.97, p=0.89). CONCLUSIONS: In mRCC
      patients treated with sunitinib, the outcome of clinical trial participants was
      similar to that of non-participants who received standard therapy.

PMID- 25761479
TI  - Antitumor Activity of HM781-36B, alone or in Combination with Chemotherapeutic
      Agents, in Colorectal Cancer Cells.
AB  - PURPOSE: HM781-36B is a novel and irreversible pan-human epidermal growth factor
      receptor (HER) inhibitor with TEC cytoplasmic kinase inhibition. The aim of this
      study is to evaluate the antitumor activity and mechanism of action for HM781-36B
      in CRC cell lines. MATERIALS AND METHODS: The CRC cell lines were exposed to
      HM781-36B and/or oxaliplatin (L-OHP), 5-fluorouracil (5-FU), SN-38. The cell
      viability was examined by Cell Titer-Glo luminescent cell viability assay kit.
      Change in the cell cycle and protein expression was determined by flow cytometry
      and immunoblot analysis, respectively. Synergism between 2 drugs was evaluated by
      the combination index. RESULTS: The addition of HM781-36B induced potent growth
      inhibition in both DiFi cells with EGFR overexpression and SNU-175 cells (IC50,
      0.003 uM and 0.005 uM, respectively). Furthermore, HM781-36B induced G1 arrest of
      the cell cycle and apoptosis, and reduced the levels of HER family and downstream
      signaling molecules, pERK and pAKT, as well as nonreceptor/cytoplasmic tyrosine
      kinase, BMX. The combination of HM781-36B with 5-FU, L-OHP, or SN-38 showed an
      additive or synergistic effect in most CRC cells. CONCLUSION: These findings
      suggest the potential roles of HM781-36B as the treatment for EGFR-overexpressing
      colon cancer, singly or in combination with chemotherapeutic agents. The role of
      BMX expression as a marker of response to HM781-36B should be further explored.

PMID- 25761480
TI  - Clinical Benefit of Hepatic Arterial Infusion Concurrent Chemoradiotherapy in
      Locally Advanced Hepatocellular Carcinoma: A Propensity Score Matching Analysis.
AB  - PURPOSE: The aim of this study was to evaluate whether hepatic arterial infusion
      concurrent chemoradiotherapy (CCRT) could improve overall survival (OS) in
      patients with locally advanced hepatocellular carcinoma (LAHCC). MATERIALS AND
      METHODS: Two databases were reviewed from Yonsei Cancer Center (YCC) and Korean
      Liver Cancer Study Group (KLCSG) nationwide multi-center hepatocellular carcinoma
      (HCC) cohort. The CCRT group included 106 patients, with stage III-IV, Child-Pugh
      classification A, Eastern Cooperative Oncology Group performance status 0 or 1,
      who underwent definitive CCRT as the initial treatment at YCC. We used propensity
      score matching to adjust for seven clinical factors, including age, tumor size,
      TNM stage by the Liver Cancer Study Group of Japan, T stage, Barcelona Clinic
      Liver Cancer (BCLC) staging system, etiology of HCC, and portal vein invasion,
      which all differed significantly in the two databases. From the KLCSG cohort
      enrolled at 32 institutions, 106 patients for the non-CCRT group were defined.
      RESULTS: After propensity score matching, all patient characteristics were
      balanced between the two groups. The CCRT group had better OS (median, 11.4) than
      the non-CCRT group (6.6 months, p=0.02). In multivariate analyses for all
      patients, CCRT (hazard ratio [HR], 1.48; 95% confidence interval [CI], 1.11 to
      1.97; p=0.007), tumor size (HR, 1.08; 95% CI, 1.04 to 1.12; p < 0.001), and BCLC
      stage (HR, 0.54; 95% CI, 0.36 to 0.8; p=0.003) were independent prognostic
      factors for OS. CONCLUSION: CCRT showed better OS for LAHCC patients. In LAHCC
      patients with a good performance and normal liver function, CCRT could be a
      feasible treatment option. All of these findings need to be validated in
      prospective clinical trials.

PMID- 25761481
TI  - The Expression of Carbonic Anhydrase (CA) IX/XII and Lymph Node Metastasis in
      Early Breast Cancer.
AB  - PURPOSE: The aim of study was to test by immunohistochemical (IHC) staining
      whether carbonic anhydrase (CA) 9 and 12 have an effect on sentinel lymph node
      (SLN) metastasis in early breast cancer and to find clinicopathologic factors
      associated with SLN metastasis. MATERIALS AND METHODS: Between June 2003 and June
      2011, medical records of 470 patients diagnosed with breast cancer with pT1-2,
      pN0-2, and M0 were reviewed. Of these 470, 314 patients who underwent SLN
      biopsy+/-axillary dissection were subjects of this study. Using tissue
      microarray, IHC staining for CA9 and CA12 was performed. Clinicopathologic
      factors such as patient age, tumour size, lymphatic invasion, hormone receptor
      status, and the Ki-67 labeling index were analysed together. RESULTS: The mean
      age of all patients was 51.7 years. The mean number of harvested SLN was 3.62,
      and 212 patients (67.5%) had negative SLN. Lymphatic invasion, the Ki-67
      labelling index of primary tumours, and CA9 staining of stromal cells, were
      independent risk factors for SLN metastasis in the multivariate analysis. In 33
      patients (10.5%) without the three risk factors, no patient had SLN metastasis.
      In 80 patients without lymphatic invasion of primary tumours or CA9 staining of
      stromal cells, only four patients (5%) had positive SLN. CONCLUSION: CA9 staining
      of stromal cells is an independent risk factor for SLN metastasis as well as
      lymphatic invasion and a low Ki-67 labelling index of primary tumours in patients
      with early breast cancer. IHC staining of primary tumours for CA12was not
      associated with SLN metastasis.

PMID- 25761482
TI  - Gefitinib-Induced Interstitial Lung Disease in Korean Lung Cancer Patients.
AB  - PURPOSE: Interstitial lung disease (ILD) is a serious adverse effect of
      gefitinib. We examined the incidence and clinical characteristics of drug-induced
      ILD in Korean non-small cell lung carcinoma patients treated with gefitinib.
      MATERIALS AND METHODS: A retrospective cohort study was performed in non-small
      cell lung cancer (NSCLC) patients who started gefitinib treatment at Seoul
      National University Hospital from January 2002 through December 2011. Patients
      who developed new abnormal radiologic findings with respiratory symptoms after
      gefitinib treatment were defined as having possible adverse pulmonary reactions.
      The patients' medical records were reviewed independently by investigators to
      identify the causes of pulmonary toxicities. RESULTS: Among the 1,114 patients
      evaluated, 128 patients (11.5%) developed pulmonary adverse reactions after
      taking gefitinib. An infectious complication occurred in 98 patients (8.8%) and
      15 patients (1.3%) developed ILD. Nine of the 15 patients (60.0%) with gefitinib
      induced ILD experienced a fatal clinical course that met either the Common
      Terminology Criteria for Adverse Events grade 4 (n=3) or grade 5 (n=6). In the
      multivariate analysis, a lower serum albumin level (<= 3.0 g/dL) at baseline was
      significantly associated with the development of gefitinib-induced ILD (odds
      ratio, 3.91; 95% confidence interval, 1.20 to 12.71). CONCLUSION: The incidence
      of gefitinib-induced ILD in Korean NSCLC patients was similar to that reported
      worldwide, but lower than values reported for Japanese population. ILD was
      usually a life-threatening adverse effect of gefitinib, and the development of
      ILD was significantly associated with a lower baseline serum albumin level.

PMID- 25761484
TI  - Cancer statistics in Korea: incidence, mortality, survival, and prevalence in
      2012.
AB  - PURPOSE: The aim of this study was to report nationwide cancer statistics in
      Korea, including incidence, mortality, survival, and prevalence, and their
      trends. MATERIALS AND METHODS: Incidence data from 1993 to 2012 were obtained
      from the Korea National Cancer Incidence Database, and vital status was followed
      through December 31, 2013. Mortality data from 1983 to 2012 were obtained from
      Statistics Korea. Crude and age-standardized rates for incidence, mortality, and
      prevalence, and relative survival were calculated. RESULTS: A total of 224,177
      cancer cases and 73,759 cancer deaths were reported in 2012, and there were
      1,234,879 prevalent cases identified in Korea as of January 1, 2013. Over the
      past 14 years (1999-2012), overall incidence rates have increased by 3.3% per
      year. The incidence rates of liver and cervical cancers have decreased, while
      those of thyroid, breast, prostate, and colorectal cancers have increased.
      Notably, incidence of thyroid cancer increased by 22.3% per year in both sexes
      and has been the most common cancer since 2009. The mortality for all cancers
      combined decreased by 2.7% per year from 2002 to 2012. Five-year relative
      survival rates of patients diagnosed in the last 5 years (2008-2012) have
      improved by 26.9% compared with those from 1993 to1995. CONCLUSION: Overall
      cancer mortality rates have declined since 2002 in Korea, while incidence has
      increased and survival has improved.

PMID- 25761483
TI  - Forkhead Transcription Factor FOXO1 Inhibits Angiogenesis in Gastric Cancer in
      Relation to SIRT1.
AB  - PURPOSE: We previously reported that forkhead transcription factors of the O
      class 1 (FOXO1) expression in gastric cancer (GC) was associated with
      angiogenesis-related molecules. However, there is little experimental evidence
      for the direct role of FOXO1 in GC. In the present study, we investigated the
      effect of FOXO1 on the tumorigenesis and angiogenesis in GC and its relationship
      with SIRT1. MATERIALS AND METHODS: Stable GC cell lines (SNU-638 and SNU-601)
      infected with a lentivirus containing FOXO1 shRNA were established for animal
      studies as well as cell culture experiments. We used xenograft tumors in nude
      mice to evaluate the effect of FOXO1 silencing on tumor growth and angiogenesis.
      In addition, we examined the association between FOXO1 and SIRT1 by
      immunohistochemical tissue array analysis of 471 human GC specimens and Western
      blot analysis of xenografted tumor tissues. RESULTS: In cell culture, FOXO1
      silencing enhanced hypoxia inducible factor-1alpha (HIF-1alpha) expression and GC
      cell growth under hypoxic conditions, but not under normoxic conditions. The
      xenograft study showed that FOXO1 downregulation enhanced tumor growth,
      microvessel areas, HIF-1alpha activation and vascular endothelial growth factor
      (VEGF) expression. In addition, inactivated FOXO1 expression was associated with
      SIRT1 expression in human GC tissues and xenograft tumor tissues. CONCLUSION: Our
      results indicate that FOXO1 inhibits GC growth and angiogenesis under hypoxic
      conditions via inactivation of the HIF-1alpha-VEGF pathway, possibly in
      association with SIRT1. Thus, development of treatment modalities aiming at this
      pathway might be useful for treating GC.

PMID- 25761485
TI  - Cross-sectional Study of Patients with Diffuse Large B-Cell Lymphoma: Assessing
      the Effect of Host Status, Tumor Burden, and Inflammatory Activity on Venous
      Thromboembolism.
AB  - PURPOSE: The risk factors for venous thromboembolism (VTE) in diffuse large B
      cell lymphoma (DLBCL) are not clear although thrombosis can be associated with
      host status, tumor burden, and inflammatory activity. We assessed the effect of
      those factors on VTE in a cross-sectional study of patients enrolled in a
      prospective cohort study. MATERIALS AND METHODS: We analyzed the occurrence of
      VTE in 322 patients with newly diagnosed DLBCL who received rituximab with
      cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) between 2008
      and 2011. Serum levels of inflammatory cytokines were measured from serum samples
      archived at diagnosis. RESULTS: With a median follow-up duration of 41.9 months,
      VTE was documented in 34 patients (10.6%). A comparison of baseline
      characteristics indicated the group with VTE had higher percentage of old age,
      stage III/IV and extranodal involvements than the group without VTE (p < 0.05).
      Thus, the International Prognostic Index was significantly associated with VTE,
      but the Khorana score was not. A univariate competing risk factor analysis for
      VTE revealed that increased levels of inflammatory cytokines such as interleukin
      (IL)-6 and IL-10 were also associated with VTE (p < 0.05) in addition to host and
      tumor burden. However, a multivariate analysis showed that two host factors
      including age (>= 60 years) and poor performance were independent risk factors
      for VTE. CONCLUSION: Among potential risk factors for VTE including tumor burden
      and inflammatory activity, age and performance status had a strong impact on the
      occurrence of VTE in patients with DLBCL who received R-CHOP.

PMID- 25761486
TI  - Current Status and Challenges of Cancer Clinical Trials in Korea.
AB  - PURPOSE: Cancer clinical trials in Korea have rapidly progressed in terms of
      quantity and quality during the last decade. This study evaluates the current
      status of cancer clinical trials in Korea and their associated problems.
      MATERIALS AND METHODS: We analyzed the clinical trials approved by the Korea Food
      and Drug Administration (KFDA) between 2007 and 2013. A nationwide on-line survey
      containing 22 questions was also performed with several cooperative study groups
      and individual researchers in 56 academic hospitals. RESULTS: The number of
      cancer clinical trials approved by the KFDA increased almost twofold from 2007 to
      2013. The number of sponsor-initiated clinical trials (SITs) increased by 50% and
      investigator-initiated clinical trials (IITs) increased by almost 640%. Three
      hundred and forty-four clinical trials were approved by the KFDA between 2012 and
      2013. At the time of the on-line survey (August 2013), 646 SITs and 519 IITs were
      ongoing in all hospitals. Six high volume hospitals were each conducting more
      than 50 clinical trials, including both SITs and IITs. Fifty-six investigators
      (31%) complained of the difficulties in raising funds to conduct clinical trials.
      CONCLUSION: The number of cancer clinical trials in Korea rapidly increased from
      2007 to 2013, as has the number of multicenter clinical trials and IITs run by
      cooperative study groups. Limited funding for IIT is a serious problem, and more
      financial support is needed both from government agencies and public donations
      from non-profit organizations.

PMID- 25761487
TI  - Intrathecal Trastuzumab Treatment in Patients with Breast Cancer and
      Leptomeningeal Carcinomatosis.
AB  - Leptomeningeal carcinomatosis is a fatal manifestation of metastatic breast
      cancer. Investigation of intrathecal (IT) trastuzumab for leptomeningeal
      carcinomatosis is currently underway; however, there has been no consensus. We
      report on two cases of human epidermal growth factor receptor 2 positive (HER2+)
      breast cancer following IT trastuzumab for leptomeningeal carcinomatosis. The
      first patient was treated with weekly IT 15 mg methotrexate plus IT 50 mg
      trastuzumab for 7 months, followed by IT trastuzumab (50 mg > 25 mg) for 18
      months. The other patient received IT trastuzumab with systemic chemotherapy
      (trastuzumab and/or paclitaxel) for 13 months. Good control of leptomeningeal
      disease was achieved with IT trastuzumab in both patients, with survival
      durations of 20 and 29 months, respectively. We suggest that IT trastuzumab is a
      promising treatment for patients with HER2+ breast cancer and leptomeningeal
      carcinomatosis. 

PMID- 25761488
TI  - Randomized Phase II Study of Pemetrexed Versus Gefitinib in Previously Treated
      Patients with Advanced Non-small Cell Lung Cancer.
AB  - PURPOSE: This study aimed to evaluate the efficacy and safety of pemetrexed
      versus gefitinib in patients with advanced non-small cell lung cancer (NSCLC)
      previously treated with chemotherapy. MATERIALS AND METHODS: Patients with
      advanced (stage IIIB or IV) or recurrent NSCLC were randomly assigned to receive
      either 500 mg/m2 of pemetrexed intravenously every 3 weeks or gefitinib 250
      mg/day orally. The primary end point was progression-free survival (PFS) at 6
      months. RESULTS: A total of 95 patients were enrolled (47 for pemetrexed and 48
      for gefitinib). Most patients were male (72%) and current/ex-smokers (69%), and
      80% had non-squamous cell carcinoma. The epidermal growth factor receptor (EGFR)
      mutation status was determined in 38 patients (40%); one patient per each arm was
      positive for EGFR mutation. The 6-month PFS rates were 22% and 15% for pemetrexed
      and gefitinib, respectively (p=0.35). Both arms showed an identical median PFS of
      2.0 months and a median overall survival (OS) of 8.5 months. In EGFR wild-type
      patients, higher response rate (RR) and longer PFS as well as OS were achieved
      via pemetrexed compared with gefitinib, although there were no significant
      differences (RR: 39% vs. 9%, p=0.07; median PFS: 6.6 months vs. 3.1 months,
      p=0.45; median OS: 29.6 months vs. 12.9 months, p=0.62). Toxicities were mild in
      both treatment arms. Frequently reported toxicities were anemia and fatigue for
      pemetrexed, and skin rash and anorexia for gefitinib. CONCLUSION: Both pemetrexed
      and gefitinib had similar efficacy with good tolerability as second-line
      treatment in unselected patients with advanced NSCLC. However, pemetrexed is
      considered more effective than gefitinib for EGFR wild-type patients.

PMID- 25761489
TI  - Decision Based on Narrow Band Imaging Cystoscopy without a Referential Normal
      Standard Rather Increases Unnecessary Biopsy in Detection of Recurrent Bladder
      Urothelial Carcinoma Early after Intravesical Instillation.
AB  - PURPOSE: The purpose of this study was to calculate the operating characteristics
      of narrowband imaging (NBI) cystoscopy versus traditional white light cystoscopy
      (WLC) in common clinical scenarios involving suspicion of bladder urothelial
      carcinoma (UC). MATERIALS AND METHODS: Sixty-three consecutive patients initially
      underwent WLC and then NBI in a single session for evaluation of microscopic
      hematuria (group I, n=20), gross hematuria (group II, n=19), and follow-up for
      prior UC (group III, n=24), by an experienced urologist. All lesions that were
      abnormal in contrast with adjacent normal mucosa were diagnosed as positive and
      biopsied. RESULTS: Sixty-six biopsies from 47 patients were performed. Pathologic
      examination showed 17 cases of UC from 21 sites. While the overall sensitivity of
      NBI was similar to that of WLC (100% vs. 94.1%), the specificity of NBI was
      significantly lower than that of WLC (50% vs. 86.9%, p < 0.001), particularly in
      group III (38.9% vs. 88.9%, p=0.004). Based on identification by NBI only, 23
      additional biopsies from 18 cases were performed for identification of one
      patient with UC, who belonged to group III. In this group, to identify this
      specific patient, 15 additional biopsies were performed from 10 patients. All
      seven cases with positive findings from NBI within 2 months after the last
      intravesical therapy were histologically proven as negative. CONCLUSION: In
      evaluation for recurrence early after intravesical instillation, the decision
      based on NBI increased unnecessary biopsy in the absence of an established
      standard for judging NBI.

PMID- 25761490
TI  - The Efficacy and Safety of Platinum/Vinorelbine as More Than Second-Line
      Chemotherapy for Advanced Non-small Cell Lung Cancer.
AB  - PURPOSE: There is no regimen that is strongly recommended for more than second
      line treatment. We investigated the efficacy and safety of platinum/vinorelbine
      as more than second-line treatment. MATERIALS AND METHODS: We selected patients
      with advanced non-small cell lung cancer (NSCLC) who received treatment with
      platinum/vinorelbine at Chungnam National University Hospital from August 2001 to
      December 2013. The primary end point was the response rate, and secondary end
      points were progression-free survival (PFS), overall survival (OS), and toxicity.
      RESULTS: Thirty-five patients were enrolled. Response rate was 22.9% (complete
      response, 0 patients [0%]; partial response, eight patients [22.9%]; stable
      disease, 10 patients [28.6%]; progressive disease, 14 patients [40.0%]). A
      significantly higher response rate was observed for patients who had responded to
      previous chemotherapy than for those who did not (34.8% [8/23] vs. 0% [0/12],
      p=0.020). The median PFS was 4 months (range, 1 to 21 months). Patients with
      adenocarcinoma and non-smokers had a significantly longer PFS than patients with
      non-adenocarcinoma and smokers (5 months vs. 2 months, p=0.007; 4.5 months vs. 2
      months, p=0.046, respectively). The median OS was 10 months (range, 1 to 41
      months). Patients with good performance status and non-smokers had a
      significantly longer OS than patients with poor performance status and smokers
      (14 months vs. 4 months, p=0.02; 18.5 months vs. 6 months, p=0.049,
      respectively). The main serious adverse event (grade 3 or 4) was neutropenia (15
      events, 13.3%) in a total of 113 cycles. CONCLUSION: Platinum/vinorelbine was
      effective as more than second-line chemotherapy, and the toxicity was tolerable,
      in patients with advanced NSCLC.

PMID- 25761491
TI  - Hypofractionated Stereotactic Radiation Therapy in Recurrent High-Grade Glioma: A
      New Challenge.
AB  - PURPOSE: The aim of this study was to evaluate outcomes of hypofractionated
      stereotactic radiation therapy (HSRT) in patients re-treated for recurrent high
      grade glioma. MATERIALS AND METHODS: From January 2006 to September 2013, 25
      patients were treated. Six patients underwent radiation therapy alone, while 19
      underwent combined treatment with surgery and/or chemotherapy. Only patients with
      Karnofsky Performance Status (KPS) > 70 and time from previous radiotherapy
      greater than 6 months were re-irradiated. The mean recurrent tumor volume was 35
      cm(3) (range, 2.46 to 116.7 cm(3)), and most of the patients (84%) were treated
      with a total dose of 25 Gy in five fractions (range, 20 to 50 Gy in 5-10
      fractions). RESULTS: The median follow-up was 18 months (range, 4 to 36 months).
      The progression-free survival (PFS) at 1 and 2 years was 72% and 34% and the
      overall survival (OS) 76% and 50%, respectively. No severe toxicity was recorded.
      In univariate and multivariate analysis extent of resection at diagnosis
      significantly influenced PFS and OS (p < 0.01). Patients with smaller recurren
      tumor volume treated had better local control and survival. Indeed, the 2-year
      PFS was 40% (<= 50 cm(3)) versus 11% (p=0.1) and the 2-year OS 56% versus 33% (>
      50 cm(3)), respectively (p=0.26). CONCLUSION: In our experience, HSRT could be a
      safe and feasible therapeutic option for recurrent high grade glioma even in
      patients with larger tumors. We believe that a multidisciplinary evaluation is
      mandatory to assure the best treatment for selected patients. Local treatment
      should also be considered as part of an integrated approach.

PMID- 25761492
TI  - Effects of er-miao-san extracts on TNF-alpha-induced MMP-1 expression in human
      dermal fibroblasts.
AB  - BACKGROUND: Various health benefits have been attributed to Er-Miao-San (EMS), a
      traditional Chinese herbal formulation that contains equal amounts of cortex
      phellodendri (Phellodendron amurense Ruprecht) and rhizoma atractylodis
      (Atractylodes lancea D.C). However, its effect on the anti-inflammatory activity
      in human dermal fibroblasts (HDFs) and the mechanism underlying this effect are
      unknown. RESULTS: This study investigated the effects of EMS on TNF-alpha-induced
      MMP-1 expression in HDFs. Our data show that EMS inhibited TNF-alpha-induced MMP
      1 expression in a concentration-dependent manner. Interestingly, EMS maintained
      IkappaB content without inhibiting the phosphorylation of MAPKs, which are well
      established upstream kinases of NF-kappaB. Moreover, EMS reduced the level of
      nuclear p65 protein in HDFs. Luciferase assay revealed that EMS inhibits the
      transcriptional activity of NF-kappaB by stabilizing IkappaB. Our results show
      that EMS exerts its anti-inflammatory effect by inhibiting NF-kappaB-regulated
      genes such as IL-1beta and IL-8. Moreover, EMS effectively inhibited TNF-alpha
      induced expression of MMP-1 via the NF-kappaB pathway. CONCLUSIONS: Taken
      together, our data suggest that EMS could potentially be used as an anti
      inflammatory and anti-aging treatment.

PMID- 25761493
TI  - Impact of atrial fibrillation on levels of high-sensitivity troponin I in a 75
      year-old population.
AB  - PURPOSE: Atrial fibrillation (AF) has been associated with elevated levels of
      cardiac troponins; however, it is not clear if this association is independent of
      underlying cardiovascular disease. The aim of this study was to investigate the
      impact of AF on cardiac troponin I levels in a 75-year-old cohort from the
      general population, using a recently introduced, highly sensitive assay. METHODS:
      All 75-year-old citizens in Asker and Baerum counties were invited to participate
      in a prevalence study of AF. High-sensitive troponin I (hs-TnI) levels were
      measured (Abbott Diagnostics) in serum samples collected from 62 subjects with AF
      and a gender-matched control group of 126 subjects in sinus rhythm. RESULTS: Hs
      TnI was detectable in all subjects (median 7.3 ng/L [range 3.0-88.7]). Patients
      with AF had higher levels than subjects in sinus rhythm (8.3 ng/L [3.7-88.7] vs.
      6.8 ng/L [3.0-77.5]; p = 0.011). Male gender (p = 0.002), hypertension (p =
      0.001), coronary heart disease (p < 0.001), heart failure (p < 0.001), prior
      stroke or transient ischemic attack (p = 0.013) and serum creatinine (p < 0.001)
      were all associated with higher levels of hs-TnI in univariate analysis. Heart
      failure and coronary heart disease remained significantly associated with hs-TnI
      in multivariate analysis, whereas the relation between AF and hs-TnI was no
      longer statistically significant. CONCLUSION: All subjects had detectable levels
      of hs-TnI. AF patients had higher hs-TnI levels than subjects in sinus rhythm;
      however, this difference was not statistically significant after adjustment for
      heart failure and coronary heart disease.

PMID- 25761494
TI  - Association between older age and outcome after cardiac surgery: a population
      based cohort study.
AB  - OBJECTIVE: Octogenarians (aged >= 80 years) are increasingly being referred for
      cardiac surgery. We aimed to describe the morbidity, mortality, and health
      services utilization of octogenarians undergoing elective cardiac surgery.
      METHODS: Retrospective population-based cohort study of adult patients receiving
      elective cardiac surgery between January 1 2004 and December 31 2009. Primary
      exposure was age >=80 years. Outcomes were 30-day, 1- and 5-year mortality, post
      operative complications, and ICU/hospital lengths of stay. Multi-variable
      logistic and Cox regression analyses were used to explore the association between
      older age and outcome. RESULTS: Of 6,843 patients receiving cardiac surgery, 544
      (7.9%) were octogenarians. There was an increasing trend in the proportion of
      octogenarians undergoing surgery during the study period (0.3% per year, P =
      0.073). Octogenarians were more likely to have combined procedures (valve plus
      coronary artery bypass or multiple valves) compared with younger strata (p <
      0.001). Crude 30-day, 1-year and 5-year mortality for octogenarians were 3.7%,
      10.8% and 29.0%, respectively. Compared to younger strata, octogenarians had
      higher adjusted 30-day (OR 4.83, 95%CI 1.30-17.92; P = 0.018) and 1-year
      mortality (OR 4.92; 95% CI, 2.32-10.46. P<0.001). Post-operative complications
      were more likely among octogenarians. Octogenarians had longer post-operative
      stays in ICU and hospital, and higher rates of ICU readmission (P < 0.001 for
      all). After multi-variable adjustment, age ? 80 years was an independent
      predictor of death at 30-days and 1 year. CONCLUSIONS: Octogenarians are
      increasingly referred for elective cardiac surgery with more combined procedures.
      Compared to younger patients, octogenarians have a higher risk of post-operative
      complications, consume greater resources, and have worse but acceptable short and
      long-term survival.

PMID- 25761495
TI  - Who should undergo a colonoscopy among patients with incidental colon uptake on
      PET-CT?
AB  - OBJECTIVES: To investigate the optimal cut-off of the maximum standard uptake
      value (SUVmax) for the detection of colorectal neoplasms and to suggest those for
      whom further colonoscopy is recommended among patients with incidental colonic
      uptake on positron emission tomography-computed tomography (PET-CT). MATERIALS
      AND METHODS: In 306 patients who underwent colonoscopy within 3 months of
      receiving PET-CT between January and December 2009, measurements of the per
      patient and per-lesion diagnostic performance of PET-CT for the detection of
      colonic neoplasms were obtained. Receiver operating characteristic (ROC) analysis
      was used to identify the SUVmax that provided a high probability of diagnosing
      malignancy and high-grade dysplasia. RESULTS: The per-patient and per-lesion PET
      CT detection sensitivities for malignancies were 93.3% (28/30; 95% confidence
      interval (CI) 76.5% to 98.9%) and 93.5% (29/31, 95% CI 77.2% to 98.9%),
      respectively; the sensitivities for high-grade dysplasia were both 90.0% (9/10;
      95% CI 54.1% to 99.5%). As a criterion to specifically detect both malignancy and
      high-grade dysplasia on focal uptake, a SUVmax greater than 2.5 yielded a 92.3%
      per-lesion sensitivity and a 42.9% per-lesion positive predictive value (PPV). In
      the ROC curve analysis, a cut-off value of SUVmax = 5.8 was established, at which
      the sensitivity, PPV and positive likelihood ratio for diagnosing malignancy and
      high-grade dysplasia were 71.8% (28/39; 95% CI 54.9% to 84.5%), 84.8% (28/33; 95%
      CI 67.3% to 94.3%) and 6.9, respectively. CONCLUSION: The optimal cut-off value
      to identify a malignancy or high-grade dysplasia was SUVmax = 5.8. However, to
      avoid missing a malignancy or high-grade dysplasia, a colonoscopy should be
      performed above a SUVmax = 2.5.

PMID- 25761496
TI  - A hybrid method to improve target registration accuracy in surgical navigation.
AB  - BACKGROUND: The accuracy of surgical navigation depends greatly on that of
      registration between the patient and the medical image. Point-based registration
      has been the most common and reliable method, which typically uses skin markers.
      Unfortunately, high registration accuracy around the markers is not sustained at
      targets deeply seated within the body. To address such increase in target
      registration error (TRE), we proposed a hybrid point-based registration method
      that incorporates anatomical landmarks near the target. MATERIAL AND METHODS:
      Ultrasound calibration is performed with an optical tracker for coordinate frame
      conversion of image coordinates into the real world. With the calibrated
      ultrasound probe, we could non-invasively obtain landmark positions near the
      target, being used together with skin markers for registration. RESULTS: In the
      experiment, we examined registration accuracies achieved with and without use of
      an anatomical landmark. We confirmed that using an additional anatomical landmark
      in registration resulted in an increase in fiducial regsitration error (FRE), but
      a significant decrease in TRE (p < 0.001). CONCLUSION: We proposed and
      demonstrated the effectiveness of a hybrid method that uses both artificial and
      anatomical landmarks for patient-to-image registration. The experimental results
      confirmed that an improvement in TRE was evident by the proposed method,
      suggesting its feasibility in various spinal surgeries.

PMID- 25761497
TI  - Sentinel lymph node biopsy using computed tomographic lymphography in patients
      with early tongue cancer.
AB  - CONCLUSIONS: Because computed tomography (CT) lymphography provides preoperative
      images of anatomic relationships between a tumor, its associated lymph vessels,
      and the sentinel lymph node (SLN), it may aid in directing the SLN biopsy for
      management of early tongue cancer. OBJECTIVES: SLN biopsy using a radioisotope
      (RI) generally has been performed in head and neck cancer. However, this method
      can be performed only at institutions that are licenced for its use. In this
      study, we evaluated the utility of performing SLN biopsy in patients with early
      tongue cancer using the newly developed technique of CT lymphography. METHODS:
      Enrolled in this study were 31 patients with T1N0 or T2N0 tongue cancer. CT
      images were obtained before and after injection of iopamidol into the peritumoral
      region and the SLN was identified as the first enhanced lymph node. SLN biopsy
      was performed using CT lymphographic guidance combined with blue dye injection.
      RESULTS: The SLN was detected by CT lymphography in 28 cases (90.3%). By
      intraoperative frozen section examination, metastases to SLNs were found in 4
      (14.3%) (T1N0, 1 patient; T2N0, 3 patients) of the 28 patients. Of these four,
      SLN micrometastases were found in one patient.

PMID- 25761498
TI  - Exploring the influence of culture on hearing help-seeking and hearing-aid
      uptake.
AB  - OBJECTIVE: The purpose of this paper was to highlight the importance of cultural
      influence in understanding hearing-help seeking and hearing-aid uptake. DESIGN:
      Information on audiological services in different countries and 'theories related
      to cross-culture' is presented, followed by a general discussion. STUDY SAMPLE:
      Twenty-seven relevant literature reviews on hearing impairment, cross-cultural
      studies, and the health psychology model and others as secondary resources.
      RESULTS: Despite the adverse consequences of hearing impairment and the
      significant potential benefits of audiological rehabilitation, only a small
      number of those with hearing impairment seek professional help and take up
      appropriate rehabilitation. Therefore, hearing help-seeking and hearing-aid
      uptake has recently become the hot topic for clinicians and researchers. Previous
      research has identified many contributing factors for hearing help-seeking with
      self-reported hearing disability being one of the main factors. Although
      significant differences in help-seeking and hearing-aid adoption rates have been
      reported across countries in population studies, limited literature on the
      influence of cross-cultural factors in this area calls for an immediate need for
      research. CONCLUSIONS: This paper highlights the importance of psychological
      models and cross-cultural research in the area of hearing help-seeking and
      hearing-aid uptake, and consequently some directions for future research are
      proposed.

PMID- 25761499
TI  - Compared with feeding infants breast milk or cow-milk formula, soy formula
      feeding does not affect subsequent reproductive organ size at 5 years of age.
AB  - BACKGROUND: Literature reports suggest that phytochemicals, such as isoflavones
      found in soybeans, impair reproductive function in animals and raise the
      possibility that consuming soy infant formula could alter hormonally sensitive
      organ development in children. OBJECTIVE: This study compared reproductive organs
      volumes and structural characteristics in children at age 5 y who were enrolled
      in the Beginnings study long-term cohort. METHODS: Breast bud, uterus, ovaries,
      prostate, and testes volumes and characteristics were assessed by ultrasonography
      in 101 children (50 boys and 51 girls) aged 5 y who were breastfed (n = 35) or
      fed cow-milk formula (n = 32) or soy formula (n = 34) as infants. Analyses were
      adjusted for race, gestational age, and birth weight. RESULTS: Among girls, no
      significant differences were found in breast bud, ovarian, or uterine volumes;
      counts of ovaries with cysts; ovarian cysts numbers; ovarian cyst size; and
      uterine shape between the diet groups. Among boys, no significant differences
      were found in breast bud, testes, or prostate volumes or structural
      characteristics between the diet groups. CONCLUSIONS: In this cohort, no early
      infant feeding effects were found on reproductive organs volumes and structural
      characteristics in children age 5 y. The follow-up of these children through
      puberty is planned and should help delineate potential early infant feeding
      effect on reproductive function later in life.

PMID- 25761500
TI  - Small Increments in Vitamin D Intake by Irish Adults over a Decade Show That
      Strategic Initiatives to Fortify the Food Supply Are Needed.
AB  - BACKGROUND: Food fortification could be an effective method of increasing vitamin
      D intakes and preventing deficiency with minimal risk of excessive dosing.
      OBJECTIVE: Secular trends in vitamin D intakes were examined over a 10-y period.
      METHODS: We compared vitamin D intakes among 18- to 64-y-old adults from the base
      diet, fortified foods, and supplements in 2 nationally representative dietary
      surveys in 1999 and 2009 implemented using the same methodology. RESULTS: There
      was a slight increase in the median (IQR) intake of vitamin D from 2.9 (3.2) to
      3.5 (3.7) MUg/d (mean +/- SD, 4.3 +/- 4.0 to 5.0 +/- 6.4 MUg). The median (IQR)
      intake from the base diet was 2.3 (1.6) MUg/d in 1999 and 2.1 (1.8) MUg/d in
      2009. In vitamin D supplement users, median (IQR) intakes were 7.6 (6.7) and 8.7
      (7.2) MUg/d and the prevalence of inadequacy decreased from 67% to 57% in 2009.
      Although the consumption of vitamin D-containing supplements was similar in the 2
      surveys (17% and 16%), the use of calcium-vitamin D supplements increased from 3%
      to 10% among women aged 50-64 y. The prevalence of fortified food consumption was
      also similar at 60%, and median (IQR) vitamin D intakes in consumers were 2.9
      (2.2) and 3.7 (2.9) MUg/d in 1999 and 2009, respectively. Mathematical modeling
      of food fortification using modified vitamin D composition data showed that there
      is potential to increase vitamin D intakes at the lower end of the distribution,
      without increasing the risk of exceeding the Tolerable Upper Intake Level.
      CONCLUSIONS: We report small increases in vitamin D intakes among Irish adults
      over a decade of focus on vitamin D and in the context of a voluntary
      fortification policy. Strategic management of vitamin D in the food supply is
      required to yield measurable benefits.

PMID- 25761501
TI  - Lysine requirements of moderately undernourished school-aged Indian children are
      reduced by treatment for intestinal parasites as measured by the indicator amino
      acid oxidation technique.
AB  - BACKGROUND: Lysine requirements of well-nourished children from developing
      regions have been found to be similar to those of children from developed regions
      (33.5 mg . kg-1 . d-1). However, intestinal parasites have been shown to increase
      lysine requirements in undernourished adults, and it is not known if a similar
      phenomenon occurs in undernourished children from poor and unsanitary
      environments. OBJECTIVE: Our objective was to measure the lysine requirement of
      moderately undernourished school-aged Indian children by the indicator amino acid
      oxidation technique before and after successful treatment for intestinal
      parasites. METHODS: Twenty-one undernourished school-aged children (~8 y of age)
      with z scores between -2 SD and -3 SD for height-for-age or weight-for-age, who
      tested positive for intestinal parasites, were studied before and after
      successful antiparasite treatment. Children were fed any 2 of 7 levels of lysine
      intakes (5, 15, 25, 35, 50, 65, and 80 mg . kg-1 . d-1) in random order. The
      lysine requirement was determined by applying a 2-phase linear regression
      crossover analysis on the fractional oxidation rate of the tracer L-[1-13C]
      phenylalanine in response to the graded lysine intakes. RESULTS: The lysine
      requirement of undernourished children with intestinal parasite infestations was
      determined to be 42.8 mg . kg-1 . d-1 (95% CI: 32.6, 53.1 mg . kg-1 . d-1), and
      after successful antiparasitic treatment it was determined to be 35.5 mg . kg-1 .
      d-1 (95% CI: 25.5, 45.5 mg . kg-1 . d-1). The results were significantly
      different (P < 0.05), although the 95% CIs overlapped. CONCLUSIONS: The lysine
      requirement in undernourished children is similar to that of well-nourished
      children, and intestinal parasitic infestation increased the lysine requirement
      by ~20%.

PMID- 25761502
TI  - Role of precursor mRNA splicing in nutrient-induced alterations in gene
      expression and metabolism.
AB  - Precursor mRNA (pre-mRNA) splicing is a critical step in gene expression that
      results in the removal of intronic sequences from immature mRNA, leading to the
      production of mature mRNA that can be translated into protein. Alternative pre
      mRNA splicing is the process whereby alternative exons and/or introns are
      selectively included or excluded, generating mature mRNAs that encode proteins
      that may differ in function. The resulting alterations in the pattern of protein
      isoform expression can result in changes in protein-protein interaction,
      subcellular localization, and flux through metabolic pathways. Although basic
      mechanisms of pre-mRNA splicing of introns and exons are reasonably well
      characterized, how these mechanisms are regulated remains poorly understood. The
      goal of this review is to highlight selected recent advances in our understanding
      of the regulation of pre-mRNA splicing by nutrients and modulation of nutrient
      metabolism that result from changes in pre-mRNA splicing. 

PMID- 25761504
TI  - Exploring the quantitative relationship between metabolism and enzymatic
      phenotype by physiological modeling of glucose metabolism and lactate oxidation
      in solid tumors.
AB  - Molecular imaging using PET or hyperpolarized MRI can characterize tumor
      phenotypes by assessing the related metabolism of certain substrates. However,
      the interpretation of the substrate turnover in terms of a pathophysiological
      understanding is not straightforward and only semiquantitative. The metabolism of
      imaging probes is influenced by a number of factors, such as the microvascular
      structure or the expression of key enzymes. This study aims to use computational
      simulation to investigate the relationship between the metabolism behind
      molecular imaging and the underlying tumor phenotype. The study focused on the
      pathways of glucose metabolism and lactate oxidation in order to establish the
      quantitative relationship between the expression of several transporters (GLUT,
      MCT1 and MCT4), expression of the enzyme hexokinase (HK), microvasculature and
      the metabolism of glucose or lactate and the extracellular pH distribution. A
      computational model for a 2D tumor tissue phantom was constructed and the spatio
      temporal evolution of related species (e.g. oxygen, glucose, lactate, protons,
      bicarbonate ions) was estimated by solving reaction-diffusion equations. The
      proposed model was tested by the verification of the simulation results using in
      vivo and in vitro literature data. The influences of different expression levels
      of GLUT, MCT1, MCT4, HK and microvessel distribution on substrate concentrations
      were analyzed. The major results are consistent with experimental data (e.g. GLUT
      is more influential to glycolytic flux than HK; extracellular pH is not
      correlated with MCT expressions) and provide theoretical interpretation of the co
      influence of multiple factors of the tumor microenvironment. This computational
      simulation may assist the generation of hypotheses to bridge the discrepancy
      between tumor metabolism and the functions of transporters and enzymes. It has
      the potential to accelerate the development of multi-modal imaging strategies for
      assessment of tumor phenotypes. 

PMID- 25761503
TI  - Dietary Fat Modifies the Effects of FTO Genotype on Changes in Insulin
      Sensitivity.
AB  - BACKGROUND: The common variants in the fat mass and obesity-associated (FTO) gene
      have been associated with obesity and insulin resistance. Recently, studies also
      linked FTO variants with macronutrient intakes. OBJECTIVE: We aimed to
      investigate whether diet interventions varying in macronutrients modified the
      effects of FTO genotypes on changes in insulin resistance. METHODS: We genotyped
      FTO variants rs1558902 and rs9939609 and measured insulin resistance in fasting
      plasma samples at baseline and at 6-mo and 2-y visits in 743 overweight or obese
      adults (aged 30-70 y, 60% women) from a randomized weight-loss dietary
      interventional trial, the Preventing Overweight Using Novel Dietary Strategies
      (POUNDS LOST) trial. We assessed interactions between FTO variants and intakes of
      dietary fat and protein in relation to change in body weight and insulin
      resistance using generalized estimating equation models. RESULTS: We found
      significant interactions between rs1558902 and dietary fat on changes in
      homeostasis model assessment of insulin resistance (HOMA-IR) and insulin (P =
      0.003 and 0.004, respectively). Each risk allele (A) of rs1558902 showed a trend
      to be related to a 0.05-unit less reduction in both log(insulin) and log(HOMA-IR)
      among the participants assigned to low-fat diets (both P = 0.06), but this was
      not significantly related to reduction in those assigned to high-fat diets (both
      P > 0.1) during the 2-y period of intervention. Our data showed that the
      association between rs9939609 and changes in insulin resistance was not modified
      by diet macronutrient intakes. CONCLUSIONS: Our results show that carriers of the
      risk alleles of rs1558902 benefit differently in improving insulin sensitivity by
      consuming high-fat weight-loss diets rather than low-fat diets. Still, given our
      data, we acknowledge it is difficult to determine whether fat or carbohydrate
      contributed to the observed associations.

PMID- 25761505
TI  - Association rate constants rationalise the pharmacodynamics of apixaban and
      rivaroxaban.
AB  - Rivaroxaban and apixaban are selective direct inhibitors of free and
      prothrombinase-bound factor Xa (FXa). Surprisingly prothrombin time (PT) is
      little sensitive to clinically relevant changes in drug concentration, especially
      with apixaban. To investigate this pharmacodynamic discrepancy we have compared
      the kinetics of FXa inhibition in strictly identical conditions (pH 7.48, 37 
      degrees C, 0.15 M). KI values of 0.74 +/- 0.03 and 0.47 +/- 0.02 nM and kon
      values of 7.3 +/- 1.6 10(6) and 2.9 +/- 0.6 10(7) M(-1) s(-1) were obtained for
      apixaban and rivaroxaban, respectively. To investigate if these constants
      rationalise the inhibitor pharmacodynamics, we used numerical integration to
      evaluate impact of FXa inhibition on thrombin generation assay (TGA) and PT.
      Simulation predicted that in TGA triggered with 20 pM tissue factor, 100 ng/ml
      apixaban or rivaroxaban increased 1.8- or 3.0-fold the lag time and 1.4- or 2.0
      fold the time to peak, whilst decreasing 1.2- or 3.1-fold the maximum thrombin
      and 1.7- or 3.5-fold the endogenous thrombin potential. These numbers were
      consistent with those obtained through the corresponding TGA triggered in plasma
      spiked with apixaban or rivaroxaban. Simulated PT ratios were also consistent
      with the corresponding plasma PT: markedly less sensitive to apixaban than to
      rivaroxaban. Analogous differences in TGA and PT were obtained irrespective of
      the drug amount added. We concluded that kon values for FXa of apixaban and
      rivaroxaban rationalise the unexpected lower sensitivity of PT and TGA to the
      former. 

PMID- 25761506
TI  - Surface vibrational structure of colloidal silica and its direct correlation with
      surface charge density.
AB  - We show that attenuated total reflection Fourier-transform infrared (ATR-FTIR)
      spectroscopy can be used to determine the surface charge density (SCD) of
      colloidal silica nanoparticles (NPs) in aqueous solution. We identify the Si-O
      stretch vibrations of neutral surface bound silanol, =Si-OH, and of the
      deprotonated group, =Si-O(-). The position of the Si-(OH) stretch vibration is
      shown to directly correlate with the NPs SCD as determined by traditional
      potentiometric titrations, shifting to lower wavenumber (cm(-1)) with increasing
      density of =Si-O(-). The origin of this shift is discussed in terms of inductive
      effects that reduce the ionic character of the Si-(OH) bond after delocalization
      of the negative charge left on a terminal =Si-O(-) group across the atoms within
      ~1 nm of the charged site. Using this new methodology, we quantitatively
      determine the SCD of 9, 14, and 25 nm diameter colloidal silica in varying
      concentrations of NaCl electrolyte at different bulk pH. This novel spectroscopic
      approach to investigate SCDs provides several opportunities for in situ coupling,
      for example, in microfluidic channels or with liquid microjets, and requires only
      very little sample-all potential advantages over a traditional potentiometric
      titration.

PMID- 25761507
TI  - Splitting a droplet for femtoliter liquid patterns and single cell isolation.
AB  - Well-defined microdroplet generation has attracted great interest, which is
      important for the high-resolution patterning and matrix distribution for chemical
      reactions and biological assays. By sliding a droplet on a patterned
      superhydrophilic/superhydrophobic substrate, tiny microdroplet arrays low to
      femtoliter were achieved with uniform volume and composition. Using this method,
      cells were successfully isolated, resulting in a single cell array. The droplet
      splitting method is facile, sample-effective, and low-cost, which will be of
      great potential for the development of microdroplet arrays for biological
      analysis as well as patterning system and devices. 

PMID- 25761509
TI  - Placental abruption and subsequent risk of pre-eclampsia: a population-based case
      control study.
AB  - BACKGROUND: Pre-eclampsia and placental abruption may share a common
      pathophysiologic mechanism, namely, uteroplacental ischaemia. The aim of this
      study was to investigate the association between placental abruption and risk of
      pre-eclampsia in a subsequent pregnancy, and to determine whether the association
      differs by the gestational age at the time of abruption. METHODS: A nested case
      control study among multiparous women in the Medical Birth Register of Finland
      from 1996-2010 was conducted. Cases of pre-eclampsia (n = 6487) and frequency
      matched controls (n = 25,948) were linked to the Hospital Discharge Registry to
      ascertain data on prior abruption. Abruption was categorised as preterm (<37
      weeks) or term (>=37 weeks) based on the gestational age at delivery. We fit
      logistic regression models to evaluate the associations between abruption and the
      odds of pre-eclampsia in the subsequent pregnancy before and after adjusting for
      potential confounders. RESULTS: Preterm abruption was associated with over a
      twofold increase in risk of pre-eclampsia [odds ratio (OR) 2.2, 95% confidence
      interval (CI) 1.5, 3.3] in a subsequent pregnancy. In contrast, term abruption
      was not associated with pre-eclampsia (OR 1.1, 95% CI 0.7, 1.7). The association
      between preterm abruption and pre-eclampsia was further elevated among women with
      a history of pre-eclampsia. Associations with preterm abruption were also
      strengthened when the outcome was pre-eclampsia with early delivery (<34 weeks).
      CONCLUSIONS: These findings suggest that placental abruption in a prior pregnancy
      is associated with a different risk profile of pre-eclampsia based on the
      gestational age of the abruption-affected pregnancy.

PMID- 25761508
TI  - Type 2 diabetes and cardiac autonomic neuropathy screening using dynamic
      pupillometry.
AB  - AIM: To determine if changes in pupillary response are useful as a screening tool
      for diabetes and to assess whether pupillometry is associated with cardiac
      autonomic neuropathy. METHODS: We conducted a cross-sectional study with
      participants drawn from two settings: a hospital and a community site. At the
      community site, individuals with newly diagnosed diabetes as well as a random
      sample of control individuals without diabetes, confirmed by oral glucose
      tolerance test, were selected. Participants underwent an LED light stimulus test
      and eight pupillometry variables were measured. Outcomes were diabetes, defined
      by oral glucose tolerance test, and cardiac autonomic dysfunction, determined by
      a positive readout on two of four diagnostic tests: heart rate response to the
      Valsalva manoeuvre; orthostatic hypotension; 30:15 ratio; and expiration-to
      inspiration ratio. The area under the curve, best threshold, sensitivity and
      specificity of each pupillometry variable was calculated. RESULTS: Data from 384
      people, 213 with diabetes, were analysed. The mean (+/-sd) age of the people with
      diabetes was 58.6 (+/-8.2) years and in the control subjects it was 56.1 (+/-8.6)
      years. When comparing individuals with and without diabetes, the amplitude of the
      pupil reaction had the highest area under the curve [0.69 (sensitivity: 78%;
      specificity: 55%)]. Cardiac autonomic neuropathy was present in 51 of the 138
      people evaluated (37.0%; 95% CI 28.8-45.1). To diagnose cardiac autonomic
      neuropathy, two pupillometry variables had the highest area under the curve:
      baseline pupil radius [area under the curve: 0.71 (sensitivity: 51%; specificity:
      84%)], and amplitude of the pupil reaction [area under the curve: 0.70
      (sensitivity: 82%; specificity: 55%)]. CONCLUSIONS: Pupillometry is an
      inexpensive technique to screen for diabetes and cardiac autonomic neuropathy,
      but it does not have sufficient accuracy for clinical use as a screening tool.

PMID- 25761511
TI  - A dynamic surface enhanced Raman spectroscopy method for ultra-sensitive
      detection: from the wet state to the dry state.
AB  - Surface-enhanced Raman spectroscopy (SERS) has been demonstrated to be an
      excellent analytical tool for a wide range of research and practical applications
      owing to its ability to achieve highly sensitive detection and provide
      fingerprint information for analytes. Improving the sensitivity of SERS is
      beneficial for the rapid analysis of target molecules in various systems, where
      the ultimate goal is to obtain quantitative analysis and detection. Considerable
      efforts have been made to develop new methods for SERS detection that improve
      upon its high sensitivity and reproducibility. In this tutorial review, we first
      introduce the traditional methods for SERS detection and then report in detail on
      the features of a new strategy for implementing SERS. This new method, namely, a
      dynamic surface-enhanced Raman spectroscopy method proposed by our group, is
      based on state translation nanoparticle-enhanced Raman spectroscopy (STNERS) from
      the wet state to the dry state. Notably, during this process, a three-dimensional
      (3D) hotspot matrix that can hold hotspots between every two adjacent particles
      in 3D space, with minimal polydispersity of the particle size and maximal
      uniformity of the interparticle distance, can be simply achieved. Experiments and
      applications using STNERS are reviewed starting with an investigation of STNERS
      mechanisms and a discussion of sample preparation. Next, evidence of the
      advantages of STNERS and practical applications are discussed. Finally, the
      future outlook for STNERS and the development of STNERS as an ultra-sensitive
      detection method are also discussed. 

PMID- 25761510
TI  - Dietary and anthropometric indicators of nutritional status in relation to
      Helicobacter pylori infection in a paediatric population.
AB  - It has been postulated that Helicobacter pylori infection could affect growth and
      appetite, consequently influencing body weight. Therefore, the association
      between H. pylori infection and the dietary and anthropometric indicators of
      nutritional status of a paediatric population were investigated. A total of 525
      children (aged 4-16 years) who were referred to the gastroenterology unit of the
      Sor Maria Ludovica Children's Hospital from Buenos Aires, Argentina, were
      enrolled and completed an epidemiological questionnaire. H. pylori infection was
      diagnosed using the 13C-urea breath test (13C-UBT). Height and weight were
      assessed for calculation of anthropometric indicators. Energy and macronutrient
      intakes were estimated by 24 h dietary recall. Data analysis was performed using
      a chi2 test, a Student's t test, a Mann-Whitney U test and linear and logistic
      regressions. The prevalence of H. pylori infection was 25.1 % (with a mean age of
      10.1 (SD 3.1) years). A tendency towards lower energy, carbohydrate, protein and
      fat intakes was observed in infected patients; however, it was not associated
      with H. pylori infection in any of the evaluated age groups (4-8, 9-13 and 14-16
      years). Underweight, stunting, overweight and obesity were also not associated
      with the infection. Although height-for-age and BMI-for-age Z scores tended to be
      lower in infected patients, the differences between H. pylori-positive and H.
      pylori-negative children were not statistically significant. In conclusion, H.
      pylori infection was not associated with dietary intake or with anthropometric
      indicators in the present population of children with gastrointestinal symptoms;
      however, an increased sample size would be needed to confirm the observed
      tendency towards lower dietary intake and lower anthropometric indicators of
      nutritional status in H. pylori-infected children.

PMID- 25761512
TI  - Disseminated superficial porokeratosis with dermal amyloid deposits in an elderly
      man: a rare entity.

PMID- 25761513
TI  - Inferior and right-sided juxtaposition of the left atrial appendage with an
      unexpected type of inter-atrial communication.
AB  - We have re-investigated an unusual cardiac specimen with juxtaposition of the
      atrial appendages. The original description dates to 1962, when the autopsy was
      performed at the Children's Memorial Hospital in Chicago, now Ann & Robert H.
      Lurie Children's Hospital of Chicago. The heart was subsequently stored in the
      Farouk S. Idriss Cardiac Registry at the same institution. The specimen shows
      usual atrial arrangement, but with the morphologically left appendage juxtaposed
      in a rightward manner, passing behind the heart rather than through the
      transverse sinus so as to reach its location inferior to the morphologically
      right appendage. The heart also demonstrated an inter-atrial communication
      between the cavities of the juxtaposed left appendage and the morphologically
      right atrium. We provide a detailed description of the morphology, and provide
      images of this lesion, which to the best of our knowledge has not previously been
      described. 

PMID- 25761514
TI  - On the importance - and unimportance - of gestational age.

PMID- 25761515
TI  - Fatty acid composition, antioxidant and antibacterial properties of the microwave
      aqueous extract of three varieties of Labisia pumila Benth.
AB  - BACKGROUND: The present study was conducted in order to evaluate the fatty acid
      profile, anti-oxidant and anti-bacterial activities from the microwave aqueous
      extract of the leaves of three different varieties of Labisia pumila Benth.
      RESULTS: The chemical analysis of the extract showed that fatty acids (palmitic,
      palmitoleic, stearic, oleic, linoleic and alpha-linolenic) acid as the main
      components in three varieties of L. pumila leaves. Furthermore, the obtained
      results of the anti-oxidant revealed that L. pumila var. alata contained higher
      anti-oxidative activities compared to var. pumila and var. lanceolata. However,
      these values were lower than the tested anti-oxidant standards. On the other
      hand, the aqueous leaf extracts in all three varieties of L. pumila were also
      found to inhibit a variable degree of antibacterial activities against eight
      bacteria (four Gram-positive and four Gram-negative bacteria). CONCLUSIONS: In
      this study, it was observed the leaves of three varieties of L. pumila exhibited
      variable patterns of fatty acids and the microwave aqueous extraction possess
      anti-oxidant and anti-bacterial activities.

PMID- 25761516
TI  - Pregnancy and perinatal outcomes in women with polycystic ovary syndrome and twin
      births: a population-based cohort study.
AB  - OBJECTIVE: To investigate pregnancy and perinatal outcomes in twin births among
      women with and without polycystic ovary syndrome (PCOS) diagnosis. DESIGN:
      Population-based cohort study. SETTING: Sweden. POPULATION: We identified 20,965
      women with twin births between 1995 and 2009 of whom 226 had a PCOS diagnosis
      through linkage between the Swedish Medical Birth Register and the Swedish
      National Patient Register. METHODS: Calculating risk ratios (RR) with 95%
      confidence intervals (CI) using a log-binomial regression model and hazard ratios
      (HR) with 95% CI for preterm birth. MAIN OUTCOME MEASURES: Preterm birth, low
      birthweight, caesarean section, pre-eclampsia, Apgar score <7 at 5 minutes and
      perinatal mortality. RESULTS: PCOS diagnosis in twin pregnancy was associated
      with increased risk of preterm delivery (51% versus 43%, RR 1.18 [95% CI 1.03
      1.37]), particularly spontaneous preterm delivery (37% versus 28%; RR 1.30 [95%
      CI 1.09-1.55]) and very preterm birth (<32 weeks) (14% versus 8%, RR 1.62 [95% CI
      1.10-2.37]). Twins of PCOS mothers had more often low birthweight (48% versus
      39%, adjusted RR 1.40 [95% CI 1.09-1.80]). This difference disappeared when
      adjusting for gestational age. No risk difference was found for caesarean
      section, pre-eclampsia, low 5-minute Apgar score or perinatal mortality.
      CONCLUSIONS: The risk of preterm delivery in twin pregnancies is increased by
      having a PCOS diagnosis. This should be considered in risk estimation and
      antenatal follow-up of twin pregnancies.

PMID- 25761517
TI  - Management of prolonged pregnancy by induction with a Foley catheter.
AB  - OBJECTIVES: To describe labor outcomes in women with prolonged pregnancy and
      induction of labor with a Foley catheter, as compared with women with spontaneous
      onset of labor. DESIGN: Retrospective study. SETTING: Helsinki University
      Hospital. SAMPLE: 553 women with uncomplicated prolonged pregnancies between
      January 2011 and January 2012, divided into 303 women (54.8%) with Foley catheter
      induction and 250 (45.2%) with spontaneous labor. METHODS: Maternal and neonatal
      characteristics of women with uncomplicated singleton pregnancy of >=41(+5) weeks
      of gestation were analyzed. MAIN OUTCOME MEASURES: Cesarean delivery rates,
      maternal and neonatal morbidity. RESULTS: The cesarean delivery rate was 30.7% (n
      = 93/303) in women with labor induction and 4.8% (12/250) in women with
      spontaneous onset of labor (p < 0.001). The cesarean delivery rate was 37.3%
      (91/244) among nulliparous women with labor induction and 8.7% (11/126) among
      women with spontaneous labor, a sixfold increased risk (odds ratio 6.2). Among
      parous women, cesarean section rates were low and not significantly different
      (3.4% vs. 0.8%, p = 0.2). There were no differences in maternal intrapartum or
      postpartum infection rates or adverse neonatal outcomes between the groups.
      CONCLUSIONS: Foley catheter induction of labor in prolonged pregnancy did not
      increase maternal or perinatal morbidity compared with spontaneous onset of labor
      but was associated with a considerably increased cesarean section rate,
      particularly among nulliparous women.

PMID- 25761519
TI  - Use of silane-functionalized graphene oxide in organic photovoltaic cells and
      organic light-emitting diodes.
AB  - Graphene oxide (GO) and silane-functionalized GO (sGO) sheets obtained through a
      simple sonication exfoliation method are employed as hole transport layers to
      improve the efficiency of organic photovoltaic (OPV) cells and organic light
      emitting diodes (OLED). GO was functionalized using (3-glycidyl
      oxypropyl)trimethoxysilane (GPTMS) and triethoxymethylsilane (MTES). The
      appearance of new peaks in the Fourier-transform infrared spectra of the sGOs
      indicates the formation of Si-O-C, Si-O-Si, Si-H, and Si-O-C moieties, which
      provide evidence of the addition of silane to the GO surface. Furthermore, the
      appearance of Si-O-Si bonds in the synchrotron radiation photoelectron spectra
      (SRPES) of the MTES-sGO and GPTMS-sGO samples suggests that silane groups were
      effectively functionalized onto the GO sheets. An OPV cell with GO layers showed
      a lower performance with a power conversion efficiency (PCE) of 2.06%; in
      contrast, OPV cells based on GPTMS-sGO and MTES-sGO have PCE values of 3.00 and
      3.08%, respectively. The OLED devices based on GPTMS-sGO and MTES-sGO showed a
      higher maximum luminance efficiency of 13.91 and 12.77 cd A(-1), respectively,
      than PEDOT:PSS-based devices (12.34 cd A(-1)). The SRPES results revealed that
      the work functions of GO, GPTMS-sGO, and MTES-sGO were 4.8, 4.9, and 5.0 eV,
      respectively. Therefore, the increase in the PCE value is attributed to improved
      band-gap alignment. It is thought that sGO could be used as an interfacial layer
      in OPV and OLED devices. 

PMID- 25761518
TI  - Tau regulates the localization and function of End-binding proteins 1 and 3 in
      developing neuronal cells.
AB  - The axonal microtubule-associated protein tau is a well-known regulator of
      microtubule stability in neurons. However, the putative interplay between tau and
      End-binding proteins 1 and 3 (EB1/3), the core microtubule plus-end tracking
      proteins, has not been elucidated yet. Here, we show that a cross-talk between
      tau and EB1/3 exists in developing neuronal cells. Tau and EBs partially
      colocalize at extending neurites of N1E-115 neuroblastoma cells and axons of
      primary hippocampal neurons, as shown by confocal immunofluorescence analyses.
      Tau down-regulation leads to a reduction of EB1/3 comet length, as observed in
      shRNA-stably depleted neuroblastoma cells and TAU-/- neurons. EB1/3 localization
      depends on the expression levels and localization of tau protein. Over-expression
      of tau at high levels induces EBs relocalization to microtubule bundles at
      extending neurites of N1E-115 cells. In differentiating primary neurons, tau is
      required for the proper accumulation of EBs at stretches of microtubule bundles
      at the medial and distal regions of the axon. Tau interacts with EB proteins, as
      shown by immunoprecipitation in different non-neuronal and neuronal cells and in
      whole brain lysates. A tau/EB1 direct interaction was corroborated by in vitro
      pull-down assays. Fluorescence recovery after photobleaching assays performed in
      neuroblastoma cells confirmed that tau modulates EB3 cellular mobility. In
      summary, we provide evidence of a new function of tau as a direct regulator of EB
      proteins in developing neuronal cells. This cross-talk between a classical
      microtubule-associated protein and a core microtubule plus-end tracking protein
      may contribute to the fine-tuned regulation of microtubule dynamics and stability
      during neuronal differentiation. We describe here a novel function for tau as a
      direct regulator of End binding (EB) proteins in differentiating neuronal cells.
      EB1/3 cellular mobility and localization in extending neurites and axons is
      modulated by tau levels and localization. We provide new evidence of the
      interplay between classical microtubule-associated proteins (MAPs) and "core"
      microtubule plus-end tracking proteins (+TIPs) during neuronal development.

PMID- 25761520
TI  - Microencapsulation of Clostridium acetobutylicum ATCC 824 spores in gellan gum
      microspheres for the production of biobutanol.
AB  - The purpose of the present study was to provide further insights on the
      applicability of microencapsulation using emulsification method, to immobilise
      Clostridium acetobutylicum ATCC 824 spores, for biobutanol production. The
      encapsulated spores were revived using heat shock treatment and the fermentation
      efficiency of the resultant encapsulated cells was compared with that of the free
      (non-encapsulated) cells. The microspheres were easily recovered from the
      fermentation medium by filtration and reused up to five cycles of fermentation.
      In contrast, the free (non-encapsulated) cells could be reused for two cycles
      only. The microspheres remained intact throughout repeated use. Although
      significant cell leakage was observed during the course of fermentation, the
      microspheres could be reused with relatively high butanol yield, demonstrating
      their role as microbial cell nurseries. Both encapsulated and liberated cells
      contributed to butanol production. 

PMID- 25761521
TI  - Development of cyclosporine A microemulsion for parenteral delivery.
AB  - The goal of this study was to develop a parenteral microemulsion formulation of
      cyclosporine A (CyA). The CyA solubility in caprylic capric triglyceride (GTCC),
      ethyl oleate and soybean oil were determined. The pseudo-ternary diagrams of oil
      (GTCC), surfactant (Solutol(r) HS-15), cosurfactants (ethanol/polyethylene glycol
      400 [PEG 400] mixture) and water were constructed to identify boundaries for
      microemulsion existence. The CyA was added at 3, 6 and 9% w/w to the optimal
      microemulsion composition. Microemulsion particle size, solution viscosity and
      conductivity were examined. The microemulsion stability and haemolytic potential
      were examined after dilution in 5% dextrose solution for injection to 1 mg/mL
      CyA. Microemulsion stability was examined after a three-month storage at 4 and 25
      degrees C. The GTCC was selected as an oil phase for CyA microemulsion based on
      solubility results. The optimum CyA microemulsion formulation consisted of 2.5%
      CyA, 9% GTCC, 24% Solutol(r) HS 15, 8% PEG 400, 4% ethanol and 52.5% water based
      on weight percent. The average particle sizes of the optimized blank and drug
      loaded microemulsions were 68.7 nm and 71.6 nm, respectively and remained
      unchanged upon 25-fold dextrose dilution. The results of microemulsion physical
      and CyA chemical were confirmed by a three-month stability study at 4 and 25 
      degrees C. In vitro haemolysis studies indicated that CyA microemulsions were
      well tolerated by erythrocytes. The novel microemulsion formulation of CyA was
      developed that is suitable for parenteral administration. This new formulation
      could potentially have less vehicle-associated side effects that current
      commercial formulation of CyA based on Cremophor(r) EL and ethanol solution. 

PMID- 25761523
TI  - Impact of limited hamstring flexibility on vertical jump, kicking speed, sprint,
      and agility in young football players.
AB  - This study aims to analyse the impact of limited hamstring flexibility (HF) on
      specific football skills, such as sprinting and jumping ability, agility, and
      kicking speed in young football players. Forty-three male football players (aged
      14-18) from a semi-professional football academy participated voluntarily in this
      study. Data about anthropometric measurements, HF (unilateral passive straight
      leg raise test: PSLR), vertical jumping ability (countermovement jump: CMJ),
      sprinting ability (5, 10, 20 m: S5 m, S10 m, S20 m), agility (Balsom agility
      test: BAT), and kicking speed in terms of ball speed (dominant and non-dominant
      leg: KSdom and KSnon-dom) were collected. Cluster analysis grouped according to
      HF, dividing participants into a flexible group (FG, n = 24) and a non-flexible
      group (NFG, n = 19) in relation to performances on the PSLR test. Despite finding
      no significant differences between groups in body composition and age, the FG
      performed better in terms of sprint scores (S5 m: 6.12%, S10 m: 4.09%, S20 m:
      3.29%), BAT score (4.11%), CMJ score (10.49%), and scores for KSdom (6.86%) and
      KSnon-dom (8%) than the NFG. The results suggest that HF is a key factor for
      performing football-specific skills, such as sprinting, jumping, agility, and
      kicking in young football players. These results support the rationale that
      muscle flexibility must be specifically trained in football players beginning at
      early ages. 

PMID- 25761524
TI  - Facebook as a medium for promoting statement of intent for organ donation: 5
      years of experience.
AB  - The number of potential registered organ donors does not cover the actual demand
      in most developed countries. Therefore, methods increasing awareness and interest
      in organ donation, including modern tools of social marketing, are being
      researched worldwide. The aim of this paper is to present our 5-year experiences
      with a Facebook networking campaign - the Dawca.pl Club. The mission of the
      campaign is to raise awareness and educate Polish society on tissue, cell, and
      organ transplants, to increase public acceptance for transplants as a treatment
      method, and to increase the number of voluntary donors signing consents for organ
      donation. The project is based on the idea of creating a community promoting
      transplantation, focused around the Dawca.pl Club. At present the club has over
      48,000 registered members - people who declared willingness to donate their
      organs after death. We present a description of members of this social networking
      service, the possibilities of using it to promote transplants and organ donation,
      and the efficacy of selected schemes for creating and publishing content on
      Facebook. The example of Dawca.pl shows that 2-way relations, spread over time,
      are required for social media to effectively engage and exert influence in a
      chosen sphere of public health and medicine. Unfortunately, at this time it is
      difficult to assess how such campaigns, apart from raising social awareness and
      acceptance, will affect the number of transplantations of organs from living and
      deceased donors.

PMID- 25761525
TI  - Centre of resistance and centre of rotation of a tooth: experimental
      determination, computer simulation and the effect of tissue nonlinearity.
AB  - The centre of resistance and centre of rotation of a tooth are key concepts in
      orthodontics. Determining the coordinates of these points is essential for
      planning orthodontic tooth movement. The paper proposes a procedure for
      experimental determination of the two centres, verifies a previously developed
      mathematical theory through computer simulations and evaluates the effect of
      nonlinearity of the periodontal ligament on the parameters related to the
      centres. The paper relies on the mathematical theory of a rigid body embedded in
      an elastic medium, physical experiment, finite element method and a simple
      nonlinear theory of the tooth. The concept of the centre of resistance requires a
      revision if nonlinearity is taken into account.

PMID- 25761522
TI  - The novel protein kinase C epsilon isoform at the adult neuromuscular synapse:
      location, regulation by synaptic activity-dependent muscle contraction through
      TrkB signaling and coupling to ACh release.
AB  - BACKGROUND: Protein kinase C (PKC) regulates a variety of neural functions,
      including neurotransmitter release. Although various PKC isoforms can be
      expressed at the synaptic sites and specific cell distribution may contribute to
      their functional diversity, little is known about the isoform-specific functions
      of PKCs in neuromuscular synapse. The present study is designed to examine the
      location of the novel isoform nPKCepsilon at the neuromuscular junction (NMJ),
      their synaptic activity-related expression changes, its regulation by muscle
      contraction, and their possible involvement in acetylcholine release. RESULTS: We
      use immunohistochemistry and confocal microscopy to demonstrate that the novel
      isoform nPKCepsilon is exclusively located in the motor nerve terminals of the
      adult rat NMJ. We also report that electrical stimulation of synaptic inputs to
      the skeletal muscle significantly increased the amount of nPKCepsilon isoform as
      well as its phosphorylated form in the synaptic membrane, and muscle contraction
      is necessary for these nPKCepsilon expression changes. The results also
      demonstrate that synaptic activity-induced muscle contraction promotes changes in
      presynaptic nPKCepsilon through the brain-derived neurotrophic factor (BDNF)
      mediated tyrosine kinase receptor B (TrkB) signaling. Moreover, nPKCepsilon
      activity results in phosphorylation of the substrate MARCKS involved in actin
      cytoskeleton remodeling and related with neurotransmission. Finally, blocking
      nPKCepsilon with a nPKCepsilon-specific translocation inhibitor peptide
      (epsilonV1-2) strongly reduces phorbol ester-induced ACh release potentiation,
      which further indicates that nPKCepsilon is involved in neurotransmission.
      CONCLUSIONS: Together, these results provide a mechanistic insight into how
      synaptic activity-induced muscle contraction could regulate the presynaptic
      action of the nPKCepsilon isoform and suggest that muscle contraction is an
      important regulatory step in TrkB signaling at the NMJ.

PMID- 25761526
TI  - Transparent free-standing film of 1-D rutile/anatase TiO2 nanorod arrays by a one
      step hydrothermal process.
AB  - Through the addition of a solid-state precursor, a large-scale, transparent, and
      free-standing film of 1-D rutile/anatase TiO2 nanorod arrays can be fabricated by
      dynamically changing the acidity and concentrations of titanium and chloride
      ions, and creating anatase growth-friendly conditions. 

PMID- 25761527
TI  - Direct Causal Networks for the Study of Transcranial Magnetic Stimulation Effects
      on Focal Epileptiform Discharges.
AB  - BACKGROUND: Transcranial magnetic stimulation (TMS) can have inhibitory effects
      on epileptiform discharges (EDs) of patients with focal seizures. However, the
      brain connectivity before, during and after EDs, with or without the
      administration of TMS, has not been extensively explored. OBJECTIVE: To
      investigate the brain network of effective connectivity during ED with and
      without TMS in patients with focal seizures. METHODS: For the effective
      connectivity a direct causality measure is applied termed partial mutual
      information from mixed embedding (PMIME). TMS-EEG data from two patients with
      focal seizures were analyzed. Each EEG record contained a number of EDs in the
      majority of which TMS was administered over the epileptic focus. As a control
      condition, sham stimulation over the epileptogenic zone or real TMS at a distance
      from the epileptic focus was also performed. The change in brain connectivity
      structure was investigated from the causal networks formed at each sliding
      window. CONCLUSION: The PMIME could detect distinct changes in the network
      structure before, within, and after ED. The administration of real TMS over the
      epileptic focus, in contrast to sham stimulation, terminated the ED prematurely
      in a node-specific manner and regained the network structure as if it would have
      terminated spontaneously.

PMID- 25761528
TI  - The relationship between benign paroxysmal positional vertigo and thyroid
      autoimmunity.
AB  - CONCLUSION: Although there have been few studies concerning BPPV and thyroid
      autoimmunity and a positive relation was found between them, this study didn't
      find any relation between BPPV and thyroid autoimmunity. IT is thought that
      further large-scale studies must be done to clarify the relation. OBJECTIVES:
      Benign paroxysmal positional vertigo (BPPV) consists of ~ 20% of vestibular
      disorders. Self-limited rotatory nystagmus with positional vertigo are the main
      findings of BPPV. Although canalolithiasis theory was confirmed by demonstrating
      freely floating debris in the endolymph of the posterior semicircular channel in
      following studies, currently, the etiology hasn't been explained totally. This
      study investigated the relation of BPPV and thyroid autoimmunity evaluated via
      measurement of serum thyroid autoantibodies. METHOD: Fifty patients (37 female,
      13 male) with BPPV (BPPV group), 52 patients (40 female, 12 male) with non-BPPV
      vertigo (non-BPPV group) and 60 otherwise normal control (38 female, 22 male)
      samples were enrolled in the study. All samples of BPPV, non-BPPV groups and
      controls had undergone a cochleovestibular test following thorough ENT
      examination. After blood samples were drawn from each subject, thyroid
      stimulating hormone (TSH), anti-thyroid peroxidase antibody (TPO-Ab) and anti
      thyroglobulin antibody (TG-Ab) levels were measured accordingly. RESULTS: In the
      study, eight patients of the BPPV group (16%) had a high thyroid antibody level.
      In the non-BPPV group, six patients (11.5%) had elevated thyroid antibodies. In
      the control group, 15 patients (25%) had elevated thyroid antibodies. TSH values
      of all subjects were detected to be within normal range. No statistical
      difference was found between the groups with respect to TG-Ab and TPO-Ab values
      (p-values = 0.729 and 0.812, respectively).

PMID- 25761529
TI  - Source geometry factors for HDR 192Ir brachytherapy secondary standard well-type
      ionization chamber calibrations.
AB  - Well-type ionization chambers are used for measuring the source strength of
      radioactive brachytherapy sources before clinical use. Initially, the well
      chambers are calibrated against a suitable national standard. For high dose rate
      (HDR) (192)Ir, this calibration is usually a two-step process. Firstly, the
      calibration source is traceably calibrated against an air kerma primary standard
      in terms of either reference air kerma rate or air kerma strength. The calibrated
      (192)Ir source is then used to calibrate the secondary standard well-type
      ionization chamber. Calibration laboratories are usually only equipped with one
      type of HDR (192)Ir source. If the clinical source type is different from that
      used for the calibration of the well chamber at the standards laboratory, a
      source geometry factor, k(sg), is required to correct the calibration coefficient
      for any change of the well chamber response due to geometric differences between
      the sources. In this work we present source geometry factors for six different
      HDR (192)Ir brachytherapy sources which have been determined using Monte Carlo
      techniques for a specific ionization chamber, the Standard Imaging HDR 1000 Plus
      well chamber with a type 70010 HDR iridium source holder. The calculated
      correction factors were normalized to the old and new type of calibration source
      used at the National Physical Laboratory. With the old Nucletron microSelectron
      v1 (classic) HDR (192)Ir calibration source, ksg was found to be in the range
      0.983 to 0.999 and with the new Isodose Control HDR (192)Ir Flexisource k(sg) was
      found to be in the range 0.987 to 1.004 with a relative uncertainty of 0.4% (k =
      2). Source geometry factors for different combinations of calibration sources,
      clinical sources, well chambers and associated source holders, can be calculated
      with the formalism discussed in this paper.

PMID- 25761530
TI  - Thrombopoietin receptor agonists significantly increase the risk of portal vein
      thrombosis in liver diseases: Meta-analysis of RCTs.

PMID- 25761532
TI  - Rotational angiography of left ventricle to guide ventricular tachycardia
      ablation.
AB  - Three-dimensional rotational angiography (3 DRA) is a novel imaging method
      introduced to guide complex catheter ablations of the left atrium. Our aim was to
      investigate the feasibility of the method in visualization of left ventricular
      anatomy and to develop a corresponding protocol for guidance of ventricular
      tachycardia ablation. We performed 3D rotational angiography in 13 patients using
      a direct left atrial protocol for data acquisition and the 3D reconstruction of
      the left ventricle was achieved in all patients. Clinical data comparison has
      proved lower use of radiation and contrast medium during 3 DRA-guided ablations
      as compared to CT-guided procedures.

PMID- 25761531
TI  - Immunomics of the koala (Phascolarctos cinereus).
AB  - The study of the koala transcriptome has the potential to advance our
      understanding of its immunome--immunological reaction of a given host to foreign
      antigens--and to help combat infectious diseases (e.g., chlamydiosis) that impede
      ongoing conservation efforts. We used Illumina sequencing of cDNA to characterize
      genes expressed in two different koala tissues of immunological importance, blood
      and spleen. We generated nearly 600 million raw sequence reads, and about 285
      million of these were subsequently assembled and condensed into ~70,000
      subcomponents that represent putative transcripts. We annotated ~16% of these
      subcomponents and identified those related to infection and the immune response,
      including Toll-like receptors (TLRs), RIG-I-like receptors (RLRs), major
      histocompatibility complex (MHC) genes, and koala retrovirus (KoRV). Using
      phylogenetic analyses, we identified 29 koala genes in these target categories
      and report their concordance with currently accepted gene groups. By mapping
      multiple sequencing reads to transcripts, we identified 56 putative SNPs in genes
      of interest. The distribution of these SNPs indicates that MHC genes (34 SNPs)
      are more diverse than KoRV (12 SNPs), TLRs (8 SNPs), or RLRs (2 SNPs). Our
      sequence data also indicate that KoRV sequences are highly expressed in the
      transcriptome. Our efforts have produced full-length sequences for potentially
      important immune genes in koala, which should serve as targets for future
      investigations that aim to conserve koala populations.

PMID- 25761533
TI  - Left atrial volume assessment in atrial fibrillation using multimodality imaging:
      a comparison of echocardiography, invasive three-dimensional CARTO and cardiac
      magnetic resonance imaging.
AB  - Left atrial size in atrial fibrillation is a strong predictor of successful
      ablation and cardiovascular events. Cardiac magnetic resonance multislice method
      (CMR-MSM) is the current gold standard for left atrial volume (LAV) assessment
      but is time consuming. We investigated whether LAV with more rapid area-length
      method by echocardiography (Echo-AL) or cardiac magnetic resonance (CMR-AL) and
      invasive measurement by 3D-CARTO mapping during ablation correlate with the CMR
      MSM. We studied 250 consecutive patients prior to atrial fibrillation ablation.
      CMR images were acquired on 3T scanner to measure LAV by MSM and biplane area
      length method. Standard echocardiography views were used to calculate LAV by
      biplane area-length method. LAV during ablation was measured by 3D-CARTO mapping.
      LAV was compared using intra-class correlation (ICC), Pearson's correlation and
      Bland-Altman plots. CMR-MSM was used as the reference standard. Mean LAV using
      CMR-MSM was 112.7 +/- 36.7 ml. CMR-AL method overestimated LAV by 13.3 +/- 21.8
      ml (11.2%, p < 0.005) whereas 3D-CARTO and Echo-AL underestimated LAV by 8.3 +/-
      22.6 and 24.0 +/- 27.6 ml respectively (8.7% and 20.0% respectively, p < 0.005).
      There was no significant difference between paroxysmal and persistent atrial
      fibrillation. CMR-AL and 3D-CARTO correlated and agreed well with CMR-MSM (r =
      0.87 and 0.74, ICC = 0.80 and 0.77 respectively). However, Echo-AL had poor
      correlation and agreement with CMR-MSM (r = 0.66 and ICC = 0.48). Bland-Altman
      plots confirmed these findings. CMR-AL method may be used as an alternative to
      CMR-MSM, as it is non-invasive, rapid, and correlates well with CMR-MSM. LAV by
      different modalities should not be used interchangeably.

PMID- 25761534
TI  - Erratum to: Binding of HIV-1 virions to alpha4beta 7 expressing cells and impact
      of antagonizing alpha4beta 7 on HIV-1 infection of primary CD4 (+) T cells.

PMID- 25761535
TI  - Suprahepatic Gallbladder.
AB  - INTRODUCTION: Suprahepatic gallbladders have been reported in the literature
      dating back to 1965. However, their etiology and consequences remain unclear.
      METHODS: A case of a patient being treated for biliary dyskinesia with an
      incidental finding of suprahepatic gallbladder is presented along with a
      literature review on the causes, effects, and management of a suprahepatic
      gallbladder. DISCUSSION: Patient underwent a robotic-assisted laparoscopic
      cholecystectomy without complications and had an uneventful recovery. Vigilance
      must be used to rule out ectopic gallbladder location in a patient with atypical
      biliary symptoms.

PMID- 25761536
TI  - Evaluation of human cord blood CD34+ hematopoietic stem cell differentiation to
      megakaryocyte on aminated PES nanofiber scaffold compare to 2-D culture system.
AB  - CONTEXT: Recently, umbilical cord blood (UCB) has been recognized as a suitable
      potential source of hematopoietic stem/progenitor cells (HSPCs) for
      transplantation. Lengthy thrombocytopenia after UCB transplantation is a major
      problem because of insufficient megakaryocyte (Mk) progenitors, which results in
      delayed platelet recovery. Frequent allogenic platelet transfusion leads to
      resistance to platelet units and higher risk of transmission of pathogenic agent.
      OBJECTIVE: Ex vivo expansion of HSPCs and their differentiation to Mk progenitors
      on aminated PES nanofiber could lead to faster platelet recovery after UCB
      transplantation. MATERIALS AND METHODS: CD34 cells were positively enriched using
      the MidiMACS system. CD34(+) cells were seeded onto conventional culture and
      aminated PES scaffold. The proliferation of CD34(+) cells, and also their
      differentiation into Mk progenitors, were evaluated. We used the flow cytometric
      method for analyzing CD41 and CD61 markers and real-time PCR for the expression
      level of transcription factors, as NF-E2 and GATA-1. RESULTS: This study
      indicated increased CD34(+) cell population in aminated PES compared to the
      conventional system. After differentiation, the amount of CD41/CD61-expressing
      cells and the quantity of NF-E2 expression level increased in the aminated PES
      versus the 2-D system. The quantity of GATA-1 expression level was reduced on
      CD41/CD61(+) cells compared to CD34(+) cells, with no difference between the
      aminated PES and the conventional system. DISCUSSION: Aminated PES nanofiber
      could have more effect on the proliferation of CD34(+) cells and Mk
      differentiation than the conventional culture. CONCLUSION: Injection of the
      expanded cells and differentiated Mk progenitors, along with the transplantation
      of UCB stem cells might accelerate recovery of platelets and decrease the period
      of thrombocytopenia after transplantation.

PMID- 25761537
TI  - Integrated logic gate for fluorescence turn-on detection of histidine and
      cysteine based on Ag/Au bimetallic nanoclusters-Cu2+ ensemble.
AB  - By means of employing 11-mercaptoundecanoic acid (11-MUA) as a reducing agent and
      protecting ligand, we present straightforward one-pot preparation of fluorescent
      Ag/Au bimetallic nanoclusters (namely AgAuNCs@11-MUA) from AgNO3 and HAuCl4 in
      alkaline aqueous solution at room temperature. It is found that the fluorescence
      of AgAuNCs@11-MUA has been selectively quenched by Cu(2+) ions, and the
      nonfluorescence off-state of the as-prepared AgAuNCs@11-MUA-Cu(2+) ensemble can
      be effectively switched on upon the addition of histidine and cysteine. By
      incorporating Ni(2+) ions and N-ethylmaleimide, this phenomenon is further
      exploited as an integrated logic gate and a specific fluorescence turn-on assay
      for selectively and sensitively sensing histidine and cysteine has been designed
      and established based on the original noncovalent AgAuNCs@11-MUA-Cu(2+) ensemble.
      Under the optimal conditions, histidine and cysteine can be detected in the
      concentration ranges of 0.25-9 and 0.25-7 MUM; besides, the detection limits are
      found to be 87 and 111 nM (S/N = 3), respectively. Furthermore, we demonstrate
      that the proposed AgAuNCs@11-MUA-based fluorescent assay can be successfully
      utilized for biological fluids sample analysis. 

PMID- 25761538
TI  - A study of the dynamics of multi-player games on small networks using territorial
      interactions.
AB  - Recently, the study of structured populations using models of evolutionary
      processes on graphs has begun to incorporate a more general type of interaction
      between individuals, allowing multi-player games to be played among the
      population. In this paper, we develop a birth-death dynamics for use in such
      models and consider the evolution of populations for special cases of very small
      graphs where we can easily identify all of the population states and carry out
      exact analyses. To do so, we study two multi-player games, a Hawk-Dove game and a
      public goods game. Our focus is on finding the fixation probability of an
      individual from one type, cooperator or defector in the case of the public goods
      game, within a population of the other type. We compare this value for both games
      on several graphs under different parameter values and assumptions, and identify
      some interesting general features of our model. In particular there is a very
      close relationship between the fixation probability and the mean temperature,
      with high temperatures helping fitter individuals and punishing unfit ones and so
      enhancing selection, whereas low temperatures give a levelling effect which
      suppresses selection. 

PMID- 25761539
TI  - Ocular adnexal (orbital) solitary fibrous tumor: nuclear STAT6 expression and
      literature review.
AB  - PURPOSE: To report the clinico-pathological features of solitary fibrous tumor
      occurring in the ocular adnexa (OA) in a single center. To assess the presence of
      NAB2-STAT6 genes fusion in OA solitary fibrous tumor detected by nuclear
      overexpression of STAT6. METHODS: Retrospective study including orbital and OA
      solitary fibrous tumors treated between 2006 and 2014 in our center. The
      clinical, radiological, and histopathological findings were evaluated. STAT6
      expression was assessed by immunohistochemistry. RESULTS: Five patients were
      identified and presented with a chronic OA mass. The tumors were radiologically
      well delimited, highly vascularized and without bone erosion. All the patients
      underwent complete surgical excision. Pathological examination confirmed solitary
      fibrous tumor in all cases. All tumors demonstrated a nuclear expression of
      STAT6. There were no recurrences, with a mean follow-up of 5 years after surgery.
      Our review demonstrated that proptosis was the most common presentation occurring
      in 60 % of the cases. In the ocular adnexa, adverse histological criteria were
      found in 19.7 % of the tumors, and recurrences were observed in 48 % of these
      cases. Thirty-six percent of patients presented at least one local recurrence,
      and metastastic spread was found in 2.4 % of the cases. Tumor-related death was
      described in two cases. CONCLUSION: Ocular adnexal SFT are rare and usually
      present as a chronic orbital mass with proptosis. In the OA, solitary fibrous
      tumor demonstrates STAT6 nuclear expression, as documented in other locations.
      Recurrences are unusual and metastasis exceptional. Initial surgical resection
      should be complete in order to avoid recurrence.

PMID- 25761540
TI  - Safety and feasibility of a strategy of early central venous catheter insertion
      in a deployed UK military Ebola virus disease treatment unit.
AB  - PURPOSE: Early central venous catheter (CVC) insertion in Ebola virus disease
      (EVD) is a novel approach and has not previously been described. This report
      delineates the safety, feasibility and clinical implications of early CVC
      insertion as the optimum means of vascular access in patients with EVD, in the
      setting of a deployed military Ebola virus disease treatment unit in Sierra
      Leone. METHODS: In the gastrointestinal phase of EVD, a 7-French 20-cm triple
      lumen CVC was inserted using aseptic technique. Data were collected prospectively
      on all cases to include baseline and subsequent blood test variables, insertion
      site and technique, and complications associated with CVC placement. RESULTS:
      Twenty-three patients underwent CVC insertion as follows: subclavian, 21 (88 %);
      internal jugular, 2 (8 %); axillary, 1 (4 %). The mean duration of CVC placement
      was 5 days. There were no significant procedure-related adverse events. Despite
      coagulopathy being present in 75 % of cases, CVC insertion was safe, and there
      was only 1 case of significant catheter site bleeding. A total of 152 needle
      venepunctures were avoided owing to the presence of a CVC, a mean of 7 (+/-3.8)
      per case over the average stay. CONCLUSION: The early use of CVCs in Ebola virus
      disease is safe, effective and facilitates patient care. It should be considered
      a feasible additional route of venous access, where physician expertise and
      resources allow.

PMID- 25761541
TI  - Erratum to: Outcome of acute mesenteric ischemia in the intensive care unit: a
      retrospective, multicenter study of 780 cases.

PMID- 25761542
TI  - The role of serum methylglyoxal on diabetic peripheral and cardiovascular
      autonomic neuropathy: the ADDITION Denmark study.
AB  - AIMS: Cardiovascular autonomic neuropathy and diabetic peripheral neuropathy are
      common diabetic complications and independent predictors of cardiovascular
      disease. The glucose metabolite methylglyoxal has been suggested to play a causal
      role in the pathogeneses of diabetic peripheral neuropathy and possibly diabetic
      cardiovascular autonomic neuropathy. The aim of this study was to investigate the
      cross-sectional association between serum methylglyoxal and diabetic peripheral
      neuropathy and cardiovascular autonomic neuropathy in a subset of patients in the
      ADDITION-Denmark study with short-term screen-detected Type 2 diabetes (duration
      ~ 5.8 years). METHODS: The patients were well controlled with regard to HbA(1c),
      lipids and blood pressure. Cardiovascular autonomic neuropathy was assessed by
      measures of resting heart rate variability and cardiovascular autonomic reflex
      tests. Diabetic peripheral neuropathy was assessed by vibration detection
      threshold (n = 319), 10 g monofilament (n = 543) and the Michigan Neuropathy
      Screening Instrument questionnaire (n = 966). Painful diabetic neuropathy was
      assessed using the Brief Pain Inventory short form (n = 882). RESULTS: No
      associations between methylglyoxal and cardiovascular autonomic reflex tests or
      any measures of diabetic peripheral neuropathy or painful diabetic neuropathy
      were observed. However, a positive association between methylglyoxal and several
      heart rate variability indices was observed, although these associations were not
      statistically significant when corrected for multiple testing. CONCLUSION: Serum
      methylglyoxal is not associated with cardiovascular autonomic neuropathy,
      diabetic peripheral neuropathy or painful diabetic neuropathy in this cohort of
      well-treated patients with short-term diabetes.

PMID- 25761543
TI  - Hierarchical composite polyaniline-(electrospun polystyrene) fibers applied to
      heavy metal remediation.
AB  - We describe the in situ preparation of a multipurpose hierarchical polyaniline
      polystyrene (PANI-PS) composite based in the chemical polymerization of PANI on
      nonwoven (NW) electrospun PS mats. We performed a detailed study of the
      properties of these materials to select the best strategies to incorporate PANI
      chains into pristine NW PS mats without compromising the original porosity and
      mechanical flexibility of the matrices. The resulting composites presented
      nanostructured PANI chains highly dispersed in the interior of the NW PS mat and
      showed good electrical properties and surface-wetting characteristics that could
      be easily controlled. In particular, we show that these NW PANI-PS mats exhibit
      interesting properties in their interaction with heavy metal ions. For instance,
      their high adsorption capacities toward dispersed Hg(II), Cd(II), Pb(II), Cr(VI),
      and Cu(II) ions make them promising materials for water remediation, by providing
      a simple manner of collecting and removing these metals from aqueous systems. In
      fact, the NW electrospun mats here presented do not suffer from the usual
      limitations found in materials commonly employed as adsorbents, such as a
      tendency to agglomerate or accumulate in the environment because of difficulties
      of properly recovering them after use. To better understand the nature of each
      pairwise metal-PANI interaction, we performed a thorough investigation of the
      optical and electrical changes induced by the metal adsorption in the NW PANI-PS
      mats. As a consequence of their interaction with the metal ions, the visual
      aspect of the mats change, a fact more evident in the case of Cr(VI) removal,
      when the matrices vary their color from green to purple. These changes are
      related to the variation of the oxidation state of the PANI chains: as the ion
      metals are progressively adsorbed into the mat, they promote the conversion in
      varying degrees of the PANI chains from salt emeraldine to the pernigraniline
      form, and the mats become more resistive. We implemented an electrical impedance
      investigation of the charge transport characteristics of NW PANI-PS mat, and the
      results indicate that they are sensitive to the type of metal ion adsorbed and
      that the amount of ions adsorbed in each case is mostly related to the standard
      electrode potential of the metal considered. 

PMID- 25761544
TI  - An estimation of the value of informal care provided to dependent people in
      Spain.
AB  - BACKGROUND AND OBJECTIVE: The aim of this paper was to arrive at an approximation
      of the value of non-professional (informal) care provided to disabled people
      living within a household in Spain. METHODS: We used the Survey on Disabilities,
      Autonomy and Dependency carried out in 2008 to obtain information about disabled
      individuals and their informal caregivers. We computed the total number of
      informal caregiving hours provided by main caregivers in Spain in 2008. The
      monetary value of informal care time was obtained using three different
      approaches: the proxy good method, the opportunity cost method and the contingent
      valuation method. RESULTS: Total hours of informal care provided in 2008 were
      estimated at 4193 million and the monetary value ranged from EUR23,064 to
      EUR50,158 million depending on the method used. The value of informal care was
      estimated at figures equivalent to 1.73-4.90 % of the gross domestic product for
      that year. CONCLUSION: Informal care represents a very high social cost
      regardless of the estimation method considered. A holistic approach to care of
      dependent people should take into account the role and needs of informal
      caregivers, promote their social recognition and lead to policies that enhance
      efficient use of formal and informal resources.

PMID- 25761546
TI  - The case of penny wise but access and quality of care foolish.

PMID- 25761545
TI  - Impact of a Dynamic Microbiological Environment on the Clinical Efficacy of
      Ertapenem and Piperacillin/Tazobactam in the Treatment of Complicated Community
      Acquired Intra-Abdominal Infection in Spain: A Cost-Consequence Analysis.
AB  - BACKGROUND AND OBJECTIVE: The microbial susceptibility of many antibiotics has
      been affected by prescribing patterns and their extensive use. The purpose of
      this evaluation was to assess how these changes could affect the initial efficacy
      of ertapenem and piperacillin/tazobactam in the treatment of complicated intra
      abdominal infections (IAIs) acquired in the community and the potential
      consequences this may have in healthcare costs in Spain. METHODS: The Initial
      efficacy of ertapenem and piperacillin/tazobactam for patients with APACHE (Acute
      Physiology and Chronic Health Evaluation) II scores <10 was extracted from a
      multicenter randomized study and were combined with the current microbial
      susceptibilities obtained from the SMART study, a multinational surveillance
      program. Country-specific pathogens distribution was extracted from a national
      study in patients with community-acquired IAI. The estimated effectiveness was
      used in a decision-analytic model to compare total costs between ertapenem and
      piperacillin/tazobactam in the treatment of complicated IAI. The model performs
      extensive one-way and probabilistic sensitivity analyses. RESULTS: The model
      suggested a savings of ?209 (year 2012 values) per patient when complicated IAIs
      acquired in the community (APACHE II <10) were treated with ertapenem instead of
      piperacillin/tazobactam. One-way sensitivity analyses showed length of stay as
      the key driver parameter. Further analysis of this parameter and probabilistic
      sensitivity analysis confirmed the robustness of our evaluation, with a 58%
      likelihood of ertapenem being dominant. CONCLUSIONS: Ertapenem appears to be a
      cost-saving strategy over piperacillin/tazobactam for the treatment of patients
      with complicated IAIs acquired in the community in Spain.

PMID- 25761547
TI  - Rescue therapy with intravitreal aflibercept for choroidal neovascularization
      secondary to choroidal osteoma non-responder to intravitreal bevacizumab and
      ranibizumab.
AB  - To investigate the effect of aflibercept in a rare case of choroidal
      neovascularization (CNV) secondary to choroidal osteoma (CO) and refractory to
      ranibizumab and bevacizumab. A 45-year-old male with CO-related CNV in his left
      eye received prior two intravitreal 1.25 mg bevacizumab injections and three
      intravitreal 0.5 mg ranibizumab injections without visual and anatomic
      improvement. Best-corrected visual acuity assessment, ophthalmic examination,
      fundus photography, and optical coherence tomography (OCT) were performed.
      Switching to intravitreal injection of 2.0 mg aflibercept was performed. After
      three loading doses of intravitreal aflibercept, visual acuity of the left eye
      improved from 20/50 to 20/32. Resolution of the persistent subfoveal fluid and
      reduction of retinal hemorrhage were confirmed according to ophthalmoscopy and
      OCT findings. No serious adverse events were observed. The treatment effect
      persisted during a 10-month follow-up period. In choroidal osteoma, switching to
      intravitreal aflibercept injection may be an effective therapeutic option for
      treatment of CNV refractory to ranibizumab and bevacizumab.

PMID- 25761548
TI  - Spectroscopy of metal-ion complexes with peptide-related ligands.
AB  - With new experimental tools and techniques developing rapidly, spectroscopic
      approaches to characterizing gas-phase metal ion complexes have emerged as a
      lively area of current research, with particular emphasis on structural and
      conformational information. The present review gives detailed attention to the
      metal-ion complexes of amino acids (and simple derivatives), much of whose study
      has focused on the question of charge-solvation vs salt-bridge modes of
      complexation. Alkali metal ions have been most frequently examined, but work with
      other metal ions is discussed to the extent to which they have been studied. The
      majority of work has been with simple cationic metal ion complexes, while recent
      excursions into deprotonated complexes, anionic complexes, and dimer complexes
      are also of interest. Interest is growing in complexes of small peptides, which
      are discussed both in the context of possible zwitterion formation as a charge
      solvation alternative, and of the alternative metal-ion bond formation to amide
      nitrogens in structures involving iminol tautomerization. The small amount of
      work on complexes of large peptides and proteins is considered, as are the
      structural consequences of solvation of the gas-phase complexes. Spectroscopy in
      the visible/UV wavelength region has seen less attention than the IR region for
      structure determination of gas-phase metal-ion complexes; the state of this field
      is briefly reviewed. 

PMID- 25761549
TI  - Chemical Protein Synthesis with the KAHA Ligation.
AB  - Since the first report of the chemoselective amide bond forming reaction between
      alpha-ketoacids and hydroxylamines in 2006, the KAHA (alpha-ketoacid
      hydroxylamine) ligation has advanced to a useful tool for the routine synthesis
      of small to medium sized proteins and cyclic peptides. In this chapter we
      introduce the concept of KAHA ligation starting with the synthesis and properties
      of hydroxylamines and alpha-ketoacids, methods for their incorporation into
      peptides, and give an insight into the mechanism of the KAHA ligation. We cover
      important improvements including sequential ligations with 5-oxaproline,
      traceless synthesis of peptide alpha-ketoacids and show their application in
      chemical protein synthesis and cyclic peptide synthesis. Recent developments of
      the KAT (potassium acyl trifluoroborate) ligation and its application as fast and
      chemoselective bioconjugation method are described and an outlook on ongoing work
      and possible future developments is given at the end of the chapter. 

PMID- 25761550
TI  - Quantitative framework for prospective motion correction evaluation.
AB  - PURPOSE: Establishing a framework to evaluate performances of prospective motion
      correction (PMC) MRI considering motion variability between MRI scans. METHODS: A
      framework was developed to obtain quantitative comparisons between different
      motion correction setups, considering that varying intrinsic motion patterns
      between acquisitions can induce bias. Intrinsic motion was considered by
      replaying in a phantom experiment the recorded motion trajectories from subjects.
      T1-weighted MRI on five volunteers and two different marker fixations (mouth
      guard and nose bridge fixations) were used to test the framework. Two metrics
      were investigated to quantify the improvement of the image quality with PMC.
      RESULTS: Motion patterns vary between subjects as well as between repeated scans
      within a subject. This variability can be approximated by replaying the motion in
      a distinct phantom experiment and used as a covariate in models comparing motion
      corrections. We show that considering the intrinsic motion alters the statistical
      significance in comparing marker fixations. As an example, two marker fixations,
      a mouth guard and a nose bridge, were evaluated in terms of their effectiveness
      for PMC. A mouth guard achieved better PMC performance. CONCLUSION: Intrinsic
      motion patterns can bias comparisons between PMC configurations and must be
      considered for robust evaluations. A framework for evaluating intrinsic motion
      patterns in PMC is presented.

PMID- 25761551
TI  - Application of a UPLC-MS/MS method for the analysis of alosetron in human plasma
      to support a bioequivalence study in healthy males and females.
AB  - A simple, rapid and sensitive ultra-performance liquid chromatography-tandem mass
      spectrometry (UPLC-MS/MS) method has been developed and validated for the
      determination of alosetron (ALO) in human plasma. The assay method involved solid
      phase extraction of ALO and ALO 13C-d3 as internal standard (IS) on a LichroSep
      DVB-HL (30 mg, 1 cm(3) ) cartridge. The chromatography was performed on an
      Acquity UPLC BEH C18 (50 * 2.1 mm, 1.7 um) column using acetonitrile and 2.0 mm
      ammonium formate, pH 3.0 adjusted with 0.1% formic acid (80:20, v/v) as the
      mobile phase in an isocratic mode. For quantitative analysis, the multiple
      reaction monitoring transitions studied were m/z 295.1/201.0 for ALO and m/z
      299.1/205.1 for IS in the positive ionization mode. The method was validated over
      a concentration range of 0.01-10.0 ng/mL for ALO. Post-column infusion experiment
      showed no positive or negative peaks in the elution range of the analyte and IS
      after injection of extracted blank plasma. The extent of ion
      suppression/enhancement, expressed as IS-normalized matrix factor, varied from
      0.96 to 1.04. The assay recovery was within 97-103% for ALO and IS. The method
      was successfully applied to support a bioequivalence study of 1.0 mg alosetron
      tablets in 28 healthy Indian male and female subjects.

PMID- 25761552
TI  - The role of carbon nanoparticles in identifying lymph nodes and preserving
      parathyroid in total endoscopic surgery of thyroid carcinoma.
AB  - AIM: To evaluate the efficacy of carbon nanoparticles (CNs) in identifying lymph
      nodes and preserving parathyroids in endoscopic total thyroidectomy (ETT) with
      central neck dissection (CND), and to further explore the role of CNs in
      recovering postoperative parathyroid function. METHOD: Fifty-five patients with
      papillary thyroid carcinoma were randomized to either CN group (n = 28) or
      control group (n = 27). The primary outcome measures were pathological results
      (e.g., amount of incidental removed parathyroids and lymph nodes dissected) and
      follow-up results [e.g., recovery of serum calcium and parathyroid hormone (PTH)
      levels]. The secondary end-points were the rates of neuromuscular symptoms, in
      hospital postoperative hormonal assay, and lymph node metastases. RESULTS: A
      total of 193 lymph nodes in the CN group and 123 lymph nodes in the control group
      were detected. The mean number of detected lymph nodes was significantly higher
      in the CN group than in the control group (P = 0.009). Parathyroids were present
      in the thyroid or central nodal specimens of five patients, which were all in the
      control group. The control group had a relatively higher incidence of incidental
      parathyroidectomy compared to the CN group (P = 0.023). Compared to the CN group,
      the incidence of paresthesia was higher in the control group even if not
      statistically significant. During follow-up, the serum calcium levels were higher
      in the CN group than in the control group; however, there was no statistically
      significant difference. For the serum PTH levels, the CN group recovered rapidly
      to the preoperative levels, whereas the control group climbed steadily to the
      normal range. The serum PTH levels in the CN group were apparently higher than in
      the control group at 1 week and 1 month postoperatively. CONCLUSION: CNs play an
      important role in protecting parathyroid glands, dissecting lymph nodes
      thoroughly, and promoting rapid recovery of parathyroid in ETT with CND (ChiCTR
      TRC-14005042).

PMID- 25761554
TI  - 2015 Scientific Session of the Society of American Gastrointestinal and
      Endoscopic Surgeons (SAGES) Nashville, Tennessee, USA, 15-18 April 2015 : Oral
      Presentations.

PMID- 25761555
TI  - 2015 Scientific Session of the Society of American Gastrointestinal and
      Endoscopic Surgeons (SAGES), Nashville, Tennessee, USA, 15-18 April 2015 : Poster
      Presentations.

PMID- 25761553
TI  - Reduced perioperative death following laparoscopic colorectal resection: results
      of an international observational study.
AB  - BACKGROUND: Laparoscopic approaches to colorectal surgery are known to accelerate
      recovery but the effect on postoperative mortality is uncertain. The purpose of
      this study was to determine whether differences exist in postoperative mortality
      between patients undergoing laparoscopic and open colorectal surgery in a group
      of international healthcare institutions. METHODS: Administrative data from 30
      worldwide institutions were searched for patients who underwent elective
      colorectal surgical resection between January 2007 and December 2011. The primary
      outcome measure was 30-day-in-hospital mortality rate. Secondary outcome measures
      were 30-day readmission rate, length of stay, and 30-day reoperation rate.
      RESULTS: There were 30,369 (20,641 colonic and 9728 rectal) resections recorded
      over the 5 years. Eight thousand eighty-six were laparoscopic (26.6%) and 22,283
      (73.4%) were open. Following propensity-score matching of the laparoscopic and
      open cohorts, mortality was 0.5% following laparoscopic colectomy and 1.2% after
      conventional surgery (P < 0.001). After adjusting for differences in preoperative
      risk factors including gender, age, comorbidity, type of surgery and diagnosis,
      by matching on propensity score, laparoscopic surgery was a strong determinant of
      reduced 30-day mortality (odds ratio 0.44; 95% confidence interval 0.31-0.62; P <
      0.001), reduced hospital stay (odds ratio 0.42, 95% confidence interval 0.39
      0.45; P < 0.001), reduced readmission (odds ratio 0.78, 95% confidence interval
      0.71-0.86; P < 0.001) and reduced re-operation (odds ratio 0.75, 95% confidence
      interval 0.65-0.76; P < 0.001). CONCLUSIONS: Minimally invasive colorectal
      surgery is associated with reduced in-hospital mortality when compared with
      conventional techniques. This finding is consistent across international
      healthcare institutions and supports efforts to disseminate laparoscopic skills.

PMID- 25761556
TI  - 14th World Congress of Endoscopic Surgery and 22nd International Congress of the
      European Association for Endoscopic Surgery (EAES) Paris, France, 25-28 June 2014
      : Oral Presentations.

PMID- 25761557
TI  - 14th World Congress of Endoscopic Surgery and 22(nd) International Congress of
      the European Association for Endoscopic Surgery (EAES) Paris, France, 25-28 June
      2014 : Poster Presentations.

PMID- 25761558
TI  - 14th World Congress of Endoscopic Surgery and 22nd International Congress of the
      European Association for Endoscopic Surgery (EAES), Paris, France, 25-28 June
      2014 : Video Presentations.

PMID- 25761559
TI  - Robot-assisted laparoscopic versus open pancreaticoduodenectomy: a prospective,
      matched, mid-term follow-up study.
AB  - BACKGROUND: Robot-assisted laparoscopic pancreaticoduodenectomy is a novel
      minimally invasive surgery technique, and its effectiveness and safety remain
      unknown in patients with borderline malignant or malignant diseases. This study
      aimed to prospectively evaluate the effectiveness and safety of RLPD versus open
      PD (OPD). METHODS: Between January 2010 and December 2013, 180 eligible patients
      were prospectively hospitalized for elective RLPD (n = 60) or OPD (n = 120). They
      were matched for tumor location, tumor type, tumor size, ASA classification, age,
      and sex. The main outcome measures included demographics, intraoperative
      variables, morbidity, postoperative recovery, and mid-term evaluation. RESULTS:
      Over the study period, the RLPD group had a significantly longer but decreasing
      operative time (median 410 vs. 323 min; P < 0.001), less blood loss (median 400
      vs. 500 mL; P = 0.005), better nutritional status recovery, expedited off-bed
      return to activity (3.2 vs. 4.8 d; P < 0.001), faster resumption of bowel
      movement (3.6 vs. 5.2 d; P < 0.001), and shorter hospital stay (20 vs. 25 d; P =
      0.002) compared to the OPD group. The two groups had similar surgical morbidities
      and mortality as well as R0 resection rate and number of lymph nodes resected.
      Among patients with pancreatic adenocarcinoma, the two groups had similar overall
      and disease-free survival (ACTRN12614000299606). CONCLUSIONS: This first largest,
      prospective matched study demonstrated that for treating selected borderline and
      malignant pathologies, RLPD was associated with a significant learning curve
      effect and expedited postoperative recovery, but had a surgical and oncological
      safety profile similar to OPD.

PMID- 25761560
TI  - Hybrid NOTES transvaginal intraperitoneal onlay mesh in abdominal wall hernias:
      an alternative to traditional laparoscopic procedures.
AB  - INTRODUCTION: Abdominal wall hernias are increasingly treated by laparoscopic
      placement of an intraperitoneal onlay mesh (IPOM). We present an alternative
      technique for women: the laparoscopic-assisted transvaginal IPOM. METHODS: Before
      surgery, all patients underwent a gynecological examination. The patients agreed
      to IPOM repair via a transvaginal approach, and written informed consent for
      surgery was obtained. Pneumoperitoneum was established with a Veress needle at
      the umbilicus. This access was subsequently dilated to 5 mm (VersaStep), and a 5
      mm laparoscope was inserted. Under laparoscopic view, the transvaginal trocars
      (12-mm VersaStep and 5-mm flexible accesses) were safely inserted after lifting
      the uterus with a uterus manipulator. After preparation of the falciform
      ligament, the ligamentum teres and the preperitoneal fat, a lightweight composite
      mesh was introduced through the transvaginal access and fixed with absorbable
      tacks using the double-crown technique. RESULTS: From September 2011 to December
      2012, we performed six laparoscopic-assisted transvaginal IPOM procedures (one
      epigastric, three umbilical, two combined epigastric and umbilical hernias; all
      were primary hernias). In the initial phase, only patients with small or medium
      primary abdominal wall hernia were selected (max. 3 cm diameter). Median hospital
      stay was 3 days (range 2-6 days). One minor complication occurred perioperatively
      (second-degree skin burn to the labia majora). At 1-year follow-up, we identified
      one recurrence in a high-risk patient with a body mass index higher than 35
      kg/m(2). No infection and no mortality were observed. CONCLUSION: Although no
      final conclusion can be made regarding the presumed non-inferiority of this
      technique in terms of recurrence and mesh infection compared with traditional
      laparoscopic IPOM, laparoscopic-assisted transvaginal IPOM is a feasible
      alternative to treat abdominal wall hernias.

PMID- 25761561
TI  - Nucleation ability of thermally reduced graphene oxide for polylactide: role of
      size and structural integrity.
AB  - Following our previous work on graphene oxide-induced polylactide (PLA)
      crystallization [Macromolecules 2010, 43, 5000-5008], in the current work, we
      further revealed the role of size and structural integrity of thermally reduced
      graphene oxide (RGO) in PLA crystallization. RGO nanoplatelets with different
      architectures were obtained via bath and probe ultrasound (RGOw and RGOp). The
      average size of RGO decreased substantially with ultrasound intensity and time,
      where the generation of RGO edges constituted the translocation of functional
      group sites from in-plane to edges. The formation of sp(3)-configuration
      dominated in RGOw, whereas the partial recovery of sp(2)-configuration occurred
      in RGOp, giving rise to either the escalation of sp(3)/sp(2) ratio for RGOw or
      retrogradation of that for RGOp. Isothermal crystallization kinetics of PLA
      nanocomposites containing RGOw and RGOp was determined by in situ synchrotron
      wide-angle X-ray diffraction. The induction period and overall crystallization
      rate of PLA/RGOw nanocomposites were strengthened with diminishing platelet size
      because of more nucleation sites encouraged by redistribution of functional
      groups. However, the adverse situation was found in PLA/RGOp nanocomposites. The
      observed phenomenon was ascribed to the disruption of the internal structure,
      i.e., the C?C sp(2) pi-bond network, which deteriorated the CH-pi interaction
      between PLA and RGO. These results conclusively suggested that the size and
      structural integrity of RGO had a concerted effort to determine the final
      nucleation ability of RGO dispersed by ultrasound.

PMID- 25761562
TI  - STAPLE: Stable Alginate Gel Prepared by Linkage Exchange from Ionic to Covalent
      Bonds.

PMID- 25761563
TI  - Unrelated donor hematopoietic stem cell transplantation for infantile enteropathy
      due to IL-10/IL-10 receptor defect.
AB  - Recent advances in genetic diagnosis have identified mutations in gene encoding
      interleukin-10 (IL-10) and IL-10 receptor (IL-10R) proteins as a cause for early
      onset enterocolitis leading to hyperinflammatory immune response. Allogeneic HSCT
      offers a potential cure; however, it was only performed in a few infants and
      mainly from family-related donors. We report a case of a girl who presented very
      early in life with severe infantile enterocolitis. Gene sequencing confirmed IL
      10R defect. Her older sister died at 13 months of age from severe undiagnosed
      enterocolitis. There was no family donor. An unrelated search identified a
      potential 10/10 high-resolution HLA-matched donor. There was some delay in donor
      activation because IL-10R defect was not on the standard list of indications for
      unrelated HSCT. Our patient received the unrelated HSCT at seven months of age,
      and she is currently nine months after transplant and doing very well. Because
      HSCT is the curative option of choice for this disorder, we encourage adding IL
      10 and IL-10R protein defects to the list of HSCT indications for unrelated donor
      procurement.

PMID- 25761564
TI  - Therapy of pyoderma gangrenosum in Germany: results of a survey among wound
      experts.
AB  - BACKGROUND: There are currently no therapeutic guidelines with respect to
      pyoderma gangrenosum (PG). MATERIAL AND METHODS: In order to systematically
      record currently practiced therapeutic options for PG, a questionnaire was
      developed and sent to experts at various German dermatology departments. RESULTS:
      Overall, 50 fully completed questionnaires were returned to us. On average, the
      diagnosis of PG is made 15 times per year. Of these patients, 11.1 % receive only
      topical therapy; 22.7 %, exclusively systemic therapy; and 66.2 %, both topical
      and systemic immunomodulatory therapy. Topically, the experts most commonly use
      class III (78 %) and class IV corticosteroids (88 %). All experts (100 %)
      reported the frequent use of systemic corticosteroids in the therapy of PG
      patients. Cyclosporine is used in 74 %, TNF-alpha inhibitors in 24 %, and
      azathioprine or mycophenolate mofetil each in 20 % of patients. Systemic agents
      such as dapsone (16 %), intravenous immunoglobulins (14 %), methotrexate (6 %),
      cyclophosphamide (4 %), tacrolimus (4 %), and rituximab (2 %), however, are given
      less frequently. CONCLUSIONS: Worldwide, no uniformly accepted standard is
      available for the treatment of patients with PG. In our survey among experts,
      treatment regimens currently used in Germany, and based on expert clinical
      experience, have now been recorded, analyzed, and benchmarked for the first time.

PMID- 25761565
TI  - HMGB1 expression and muscle regeneration in idiopathic inflammatory myopathies
      and degenerative joint diseases.
AB  - The High-Mobility Group Box 1 protein (HMGB1) is a known nuclear protein which
      may be released from the nucleus into the cytoplasm and the extracellular space.
      It is believed that the mobilized HMGB1 plays role in the autoimmune processes as
      an alarmin, stimulating the immune response. In addition, muscle regeneration and
      differentiation may also be altered in the inflammatory surroundings. Biopsy
      specimens derived from patients with idiopathic inflammatory myopathies (IIM)
      such as polymyositis or dermatomyositis were compared to muscle samples from
      patients undergoing surgical interventions for coxarthrosis. The biopsy and
      surgery specimens were used for Western blot analysis, for immunohistochemical
      detection of HMGB1 in histological preparations and for cell culturing to examine
      cell proliferation and differentiation. Our data show lower HMGB1 expression,
      impaired proliferation and slightly altered fusion capacity in the primary cell
      cultures started from IIM specimens than in cultures of coxarthrotic muscles. The
      ratio of regenerating muscle fibres with centralised nuclei (myotubes) is lower
      in the IIM samples than in the coxarthrotic ones but corticosteroid treatment
      shifts the ratio towards the coxarthrotic value. Our data suggest that the
      impaired regeneration capacity should also be considered to be behind the muscle
      weakness in IIM patients. The role of HMGB1 as a pathogenic signal requires
      further investigation. 

PMID- 25761567
TI  - Risky sexual behaviour among adolescents may be related to ADHD.

PMID- 25761566
TI  - The location and translocation of ndh genes of chloroplast origin in the
      Orchidaceae family.
AB  - The NAD(P)H dehydrogenase complex is encoded by 11 ndh genes in plant chloroplast
      (cp) genomes. However, ndh genes are truncated or deleted in some autotrophic
      Epidendroideae orchid cp genomes. To determine the evolutionary timing of the
      gene deletions and the genomic locations of the various ndh genes in orchids, the
      cp genomes of Vanilla planifolia, Paphiopedilum armeniacum, Paphiopedilum niveum,
      Cypripedium formosanum, Habenaria longidenticulata, Goodyera fumata and
      Masdevallia picturata were sequenced; these genomes represent Vanilloideae,
      Cypripedioideae, Orchidoideae and Epidendroideae subfamilies. Four orchid cp
      genome sequences were found to contain a complete set of ndh genes. In other
      genomes, ndh deletions did not correlate to known taxonomic or evolutionary
      relationships and deletions occurred independently after the orchid family split
      into different subfamilies. In orchids lacking cp encoded ndh genes, non cp
      localized ndh sequences were identified. In Erycina pusilla, at least 10
      truncated ndh gene fragments were found transferred to the mitochondrial (mt)
      genome. The phenomenon of orchid ndh transfer to the mt genome existed in ndh
      deleted orchids and also in ndh containing species. 

PMID- 25761569
TI  - The temporal distribution, source and potential toxicity of polycyclic aromatic
      hydrocarbons in a sediment core from an urban lake in Wuhan, China.
AB  - The urban lakes in China, especially those with relatively small areas and closed
      watersheds, have suffered from serious pollution and are at a high risk of
      eutrophication due to the small amount of concern given to them. The temporal
      distribution profile, source apportionment and potential toxicity of parent
      polycyclic aromatic hydrocarbons (PAHs) and alkylated PAHs (APAHs) in a sediment
      core from an urban shallow lake with the above specifications, in the middle and
      lower reaches of the Yangtze River, China, were investigated in the present
      study. Parent PAHs, especially 4-6 ring ones, were dominant in the sediment core.
      The vertical profiles of 16 anthropogenic US Environmental Protection Agency
      (EPA) priority PAHs increased from a depth of 50 cm to 30 cm, then slightly
      decreased to the surface. However, biogenic perylene content decreased from
      bottom to surface. Most of the APAHs increased in concentration from bottom to
      surface. Source apportionment of EPA PAHs indicated the pyrogenic source was
      dominant in the sediment core. The domestic combustion of bituminous coal, coal
      tar and biomass can be identified as the main factors responsible for this.
      Toxicity assessment of selected parent PAHs demonstrated that benzo(a)pyrene
      accounted for the largest part of the toxic equivalent quantity (TEQ), and PAHs
      in the studied area possibly imposed adverse biological effects, especially for
      benthic organisms. Therefore, action should be taken to prevent an increase in
      the contamination from PAHs in the studied area, as well as in similar urban
      lakes in China, based on the specificity of individual watersheds. 

PMID- 25761568
TI  - The anthelmintic efficacy of natural plant cysteine proteinases against the rat
      tapeworm Hymenolepis diminuta in vivo.
AB  - Hymenolepis diminuta is a natural parasite of the common brown rat Rattus
      norvegicus, and provides a convenient model system for the assessment of the
      anthelmintic activity of novel drugs against cestodes. The experiments described
      in this paper indicate that treatment of rats infected with H. diminuta with a
      supernatant extract of papaya latex, containing a mixture of four cysteine
      proteinases, was moderately efficacious, resulting in a significant, but
      relatively small, reduction in worm burden and biomass. However, faecal egg
      output was not affected by treatment. In our experiments these effects were only
      partially dose-dependent, although specific inhibition by E-64 confirmed the role
      of cysteine proteinases as the active principles in papaya latex affecting worm
      growth but not statistically reducing worm burden. Data collected for a further 7
      days after treatment indicated that the effects of papaya latex supernatant on
      worm loss and on worm growth were not enhanced. Our findings provide a starting
      point for further refinement in formulation and delivery, or assessment of
      alternative natural plant-derived cysteine proteinases in efforts to develop
      these naturally occurring enzymes into broad-spectrum anthelmintics, with
      efficacy against cestodes as well as nematodes. 

PMID- 25761570
TI  - Asthma and height in twins: a cohort and within-pair analyses study.
AB  - In singletons, asthma may be associated with shorter height and delayed growth
      during adolescence. Yet, these studies do not account for heritability of asthma,
      puberty/menarche, and height. We aimed to study the association between asthma
      and puberty in boys and menarche in girls, and height, in a cohort of twins and
      subsequently in same-sex twin pairs discordant for asthma. From a Swedish twin
      cohort, parent- and self-reported data on asthma, puberty/menarche, and height
      were collected. Pubertal staging was established via the Petersen index. Logistic
      and linear regression was used to estimate associations between asthma and
      puberty/menarche and height, respectively. For within-pair analyses in twins
      discordant for asthma, conditional logistic and linear regression were used. Data
      on 2,658 (49.1% boys) twins were included. Among boys, asthma prevalence was 8.2%
      at 8-9 years and 10.2% at 13-14 years. Corresponding numbers for girls were 4.2%
      and 4.9%, respectively. In the entire cohort, no statistically significant
      associations were found between current asthma and puberty/menarche. Boys with
      asthma were shorter than boys without asthma at 8-9 years (on average, 1.86 [0.17
      3.56] cm, p = .03) and at 13-14 years (on average, 2.94 [0.98-4.91] cm, p = .003)
      but not at 19-20 years. No such associations were found for girls. Within same
      sex twin pairs discordant for asthma, no statistically significant associations
      were found for either sex. Twin boys, but not girls, with asthma were shorter
      than those without asthma. Non-statistically significant estimates from within
      pair analyses suggest the association is partly confounded by genetic or familial
      environmental factors. 

PMID- 25761572
TI  - Methods for surveillance of fetal alcohol syndrome: The Fetal Alcohol Syndrome
      Surveillance Network II (FASSNetII) - Arizona, Colorado, New York, 2009 - 2014.
AB  - Surveillance of fetal alcohol syndrome (FAS) is important for monitoring the
      effects of prenatal alcohol exposure and describing the public health burden of
      this preventable disorder. Building on the infrastructure of the Fetal Alcohol
      Syndrome Surveillance Network (FASSNet, 1997-2002), in 2009 the Centers for
      Disease Control and Prevention awarded 5-year cooperative agreements to three
      states, Arizona, Colorado, and New York, to conduct population-based surveillance
      of FAS. The Fetal Alcohol Syndrome Surveillance Network II (FASSNetII, 2009-2014)
      developed a surveillance case definition based on three clinical criteria:
      characteristic facial features, central nervous system abnormalities, and growth
      deficiency. FASSNetII modified the FASSNet methods in three important ways: (1)
      estimation of a period prevalence rather than birth prevalence; (2) surveillance
      of FAS among school-age children (ages 7-9 years) to better document the central
      nervous system abnormalities that are not apparent at birth or during infancy;
      and (3) implementation of an expert clinical review of abstracted data for
      probable and confirmed cases classified through a computerized algorithm.
      FASSNetII abstracted data from multiple sources including birth records, medical
      records from child development centers or other specialty clinics, and
      administrative databases such as hospital discharge and Medicaid. One challenge
      of FASSNetII was its limited access to non-medical records. The FAS prevalence
      that could be estimated was that of the population identified through an
      encounter with the healthcare system. Clinical and public health programs that
      identify children affected by FAS provide critical information for targeting
      preventive, medical and educational services in this vulnerable population.

PMID- 25761571
TI  - Individual Differences in Cue-Induced Motivation and Striatal Systems in Rats
      Susceptible to Diet-Induced Obesity.
AB  - Pavlovian cues associated with junk-foods (caloric, highly sweet, and/or fatty
      foods), like the smell of brownies, can elicit craving to eat and increase the
      amount of food consumed. People who are more susceptible to these motivational
      effects of food cues may have a higher risk for becoming obese. Further,
      overconsumption of junk-foods leading to the development of obesity may itself
      heighten attraction to food cues. Here, we used a model of individual
      susceptibility to junk-foods diet-induced obesity to determine whether there are
      pre-existing and/or diet-induced increases in attraction to and motivation for
      sucrose-paired cues (ie, incentive salience or 'wanting'). We also assessed diet-
      vs obesity-associated alterations in mesolimbic function and receptor expression.
      We found that rats susceptible to diet-induced obesity displayed heightened
      conditioned approach prior to the development of obesity. In addition, after junk
      food diet exposure, those rats that developed obesity also showed increased
      willingness to gain access to a sucrose cue. Heightened 'wanting' was not due to
      individual differences in the hedonic impact ('liking') of sucrose.
      Neurobiologically, Mu opioid receptor mRNA expression was lower in striatal 'hot
      spots' that generate eating or hedonic impact only in those rats that became
      obese. In contrast, prolonged exposure to junk-food resulted in cross
      sensitization to amphetamine-induced locomotion and downregulation of striatal
      D2R mRNA regardless of the development of obesity. Together these data shed light
      on individual differences in behavioral and neurobiological consequences of
      exposure to junk-food diets and the potential contribution of incentive
      sensitization in susceptible individuals to greater food cue-triggered
      motivation. 

PMID- 25761573
TI  - Lrrk2 R1628P variant is a risk factor for essential tremor.
AB  - Essential tremor (ET) and Parkinson's disease (PD) are two of the most common
      adult onset movement disorders with overlapping clinical features. PD patients
      with leucine-rich repeat kinase-2 (LRRK2) mutations may present initially with an
      ET phenotype. To address the possibility of a common genetic link between ET and
      PD, we examined the association between a common LRRK2 R1628P gene variant and
      ET. The LRRK2 R1628P was genotyped in ET cases and matched healthy controls. A
      total of 1277 subjects comprising of 450 ET cases and 827 controls were included.
      There were 40 heterozygote (GG to CG) variant out of 450 ET cases (genotypic
      frequency 8.9%) and 36 heterozygote variant (GG to CG, genotypic frequency 4.3%)
      and one homozygote variant (GG to CC) out of 827 controls. Subjects carrying the
      R1628P variant had a twofold increased risk of ET (p = 0.0035, OR = 2.20 and 95%
      confidence interval is 1.30-3.73). Using a case control methodology, we
      demonstrated an association between a known PD risk variant, LRRK2 R1628P, with
      ET. Subjects carrying the R1628P variant had twice the risk of developing ET. The
      sharing of a similar gene risk variant suggests a possible pathophysiologic link
      between PD and ET. 

PMID- 25761574
TI  - A novel de novo 20q13.32-q13.33 deletion in a 2-year-old child with poor growth,
      feeding difficulties and low bone mass.
AB  - Interstitial deletions of the long arm of chromosome 20 are rarely reported in
      the literature. We report a 2-year-old child with a 2.6 Mb deletion of 20q13.32
      q13.33, detected by microarray-based comparative genomic hybridization, who
      presented with poor growth, feeding difficulties, abnormal subcutaneous fat
      distribution with the lack of adipose tissue on clinical examination, facial
      dysmorphism and low bone mass. This report adds to rare publications describing
      constitutional aberrations of chromosome 20q, and adds further evidence to the
      fact that deletion of the GNAS complex may not always be associated with an
      Albright's hereditary osteodystrophy phenotype as described previously.

PMID- 25761575
TI  - Older individuals heterozygous for a growth hormone-releasing hormone receptor
      gene mutation are shorter than normal subjects.
AB  - Growth hormone (GH)-releasing hormone (GHRH) is the most important stimulus for
      GH secretion by the pituitary gland. Subjects homozygous for GHRH receptor
      (GHRHR) gene (GHRHR) inactivating mutations have severe GH deficiency, resulting
      in severe short stature if not treated. We previously reported that young adults
      heterozygous for the c.57+1G>A null GHRHR mutation (MUT/N) have reduced weight
      and body mass index (BMI) but normal stature. Here we have studied whether older
      MUT/N have an additional phenotype. In a cross-sectional study, we measured
      height, weight and blood pressure, and calculated BMI in two groups (young, 20-40
      years of age) and old (60-80 years) of individuals heterozygous for the same
      GHRHR mutation, and compared with a large number of individuals of normal
      genotype residing in the same geographical area. Standard deviation score (SDS)
      of weight was lower, and BMI had a trend toward reduction in young heterozygous
      compared with young normals, without significant difference in stature.
      Conversely, SDS of height was lower in older heterozygous individuals than in
      controls, corresponding to a reduction of 4.2 cm. These data show a reduced
      stature in older subjects heterozygous for the c.57+1G>A GHRHR mutation,
      indicating different effects of heterozygosis through lifespan.

PMID- 25761576
TI  - Self-gated tissue phase mapping using golden angle radial sparse SENSE.
AB  - PURPOSE: To investigate the combination of Golden Angle Radial Sparse SENSE
      reconstruction with image-based self-gating (SG) for deriving high-quality TPM
      data from radial golden angle (GA) k-space data. METHODS: In 10 healthy
      volunteers, a self-gated radial GA TPM sequence (TPMSG ) was compared with a
      prospectively triggered radial TPM acquisition with conventional respiratory
      (RNAV) compensation (TPMref ). Image quality and velocities were compared for
      different regularization strengths lambda in the CS reconstruction. RESULTS:
      Acquisitions and retrospective self-gating was successful in all cases. Contrast
      in TPMSG was superior to TPMref , because the blood saturation bands could be
      applied with full thickness without interference with the RNAV. Velocities from
      both acquisitions visually showed the same motion patterns and were
      quantitatively highly similar (correlation 0.81-0.97 and RMSE 0.08-0.21 cm/s).
      Strong temporal regularization ( lambda?0.3,0.4) led to reduced velocity peaks in
      TPMSG . For lambda=0.2, image sharpness as well as velocity peaks of TPMSG were
      comparable to TPMRef . CONCLUSION: The combination of Golden Angle Radial Sparse
      SENSE with image-based self-gating allows measurement of velocities of the
      myocardium with superior black-blood contrast and full coverage of the cardiac
      cycle.

PMID- 25761578
TI  - Glaucoma: basic science and clinical translation.

PMID- 25761577
TI  - Rightward-biased hemodynamic response of the parahippocampal system during
      virtual navigation.
AB  - Phase reset of parahippocampal electrophysiological oscillations in the theta
      frequency range is said to contribute to item encoding and retrieval during
      spatial navigation. Although well-studied in non-human animals, this mechanism is
      poorly understood in humans. Previously we found that feedback stimuli presented
      in a virtual maze environment elicited a burst of theta power over right
      posterior areas of the human scalp, and that the power and phase angle of these
      oscillations were greater following right turns compared to left turns in the
      maze. Here we investigated the source of this effect with functional magnetic
      resonance imaging. Consistent with our predictions, we found that 1) feedback
      encountered in the maze task activated right parahippocampal cortex (PHC), 2)
      right PHC was more activated by rewards following right turns compared to left
      turns in the maze, and 3) the rightward-biased activation was more pronounced in
      individuals who displayed good spatial abilities. These findings support our
      previous electrophysiological findings and highlight, in humans, a role for PHC
      theta oscillations in encoding salient information for the purpose of spatial
      navigation. 

PMID- 25761579
TI  - Glutathione attenuates nitric oxide-induced retinal lipid and protein changes.
AB  - BACKGROUND: Elevated levels of nitric oxide (NO(*) ), a pro-oxidant that has been
      associated with numerous retinal diseases, have been implicated in experimental
      glaucoma models. This study investigated the oxidative effects of sodium
      nitroprusside (SNP), a nitric oxide donor, on the retinal lipids and proteins and
      evaluated the potential protective effects of glutathione (GSH). METHODS: Porcine
      retinal homogenates were incubated with 0, 1, 2, 3, 4 and 5 MUm SNP.
      Malondialdehyde (MDA) levels were assayed spectrophotometrically to quantify
      lipid peroxidation. Differential protein expressions of 3 MUm SNP-treated retinal
      homogenates were compared with controls after the conduction of two-dimensional
      gel electrophoresis. Mass spectrometric data was used to identify proteins in
      NCBInr database. Furthermore, GSH was co-incubated with 3 MUm SNP-treated retinal
      homogenates. MDA levels and protein expressions were compared with SNP-treated
      controls. RESULTS: SNP significantly increased retinal-MDA levels (p = 0.0002). 2
      D gel electrophoresis images displayed a significant change in 13 protein spot
      expressions (p < 0.05). GSH suppressed SNP-induced MDA elevation (p < 0.0001) and
      selected protein changes (p < 0.05). SNP down-regulated paraoxonase/arylesterase
      2 precursor (PON2), beta-actin and beta-tubulin; however, these effects were
      prevented by a co-incubation with GSH, as confirmed by Western blots.
      CONCLUSIONS: Nitric oxide induced lipid and protein changes in retinal tissues.
      The effects were partially reversed by co-incubation with GSH. Data from this
      study suggests that nitric oxide-induced retinal oxidative stress induces
      specific molecular changes. This may enable us to better understand the
      pathogenesis of glaucoma. Further studies are indicated to explore potential
      pharmacological applications of GSH in nitric oxide-related retinal diseases.

PMID- 25761580
TI  - Repeatability and comparison of clinical techniques for anterior chamber angle
      assessment.
AB  - PURPOSE: To assess the repeatability of gonioscopy, van Herick method and
      anterior segment Optical Coherence Tomography (AS-OCT) and determine the
      agreement between these techniques within a community optometry setting. METHODS:
      Gonioscopy, van Herick method and AS-OCT imaging were performed by an optometrist
      on two occasions, 1 month apart, on 80 subjects aged over 40 years recruited from
      community optometry practices. Anterior segment images were captured with a
      spectral domain OCT (Topcon 3D OCT-2000; wavelength 840 nm) set to the Anterior
      Segment (AS) mode. Eyes were graded as open or occludable for each method. AS-OCT
      images from both visits were graded by a second optometrist masked to the
      gonioscopy and van Herick method results, and the visit on which the images were
      acquired. Cohen's kappa (kappa) was used to describe the intra-observer
      repeatability. Likelihood ratios, sensitivity and specificity of van Herick
      method and AS-OCT were calculated, using gonioscopy as the reference standard.
      RESULTS: Measurements were obtained from 80 eyes of 80 subjects. In four cases,
      AS-OCT images were un-gradable due to difficulty in locating the scleral spur.
      The repeatability of gonioscopy was fair kappa = 0.29, while that of the van
      Herick method (kappa = 0.54) and AS-OCT (kappa = 0.47) were somewhat better. The
      van Herick method showed good sensitivity (visit 1: 75%, visit 2: 69%) and high
      specificity (visit 1: 88%, visit 2: 96%). The sensitivity of AS-OCT was fair
      (visit 1: 46%, visit 2: 25%), but specificity was high (visit 1: 87%. visit 2:
      89%). CONCLUSION: Intra-observer repeatability was better for van Herick method
      and for AS-OCT than for gonioscopy, despite the latter being considered the gold
      standard method. The van Herick method appeared to be more sensitive than AS-OCT
      when identifying eyes at risk of angle closure. A standalone anterior segment OCT
      with a longer wavelength laser could afford better visualisation of the angle,
      and might therefore be expected to enable the examiner to make more precise
      classifications. These instruments are not widely used by optometrists in
      clinical practice in the UK at present.

PMID- 25761581
TI  - Modern disposable hydrogel contact lens removal has a minimal effect on
      intraocular pressure.
AB  - PURPOSE: To determine whether the removal of modern disposable hydrogel contact
      lenses may influence intraocular pressure (IOP) measurement, and if so, how long
      the effect may last. METHODS: Twenty-five healthy experienced contact lens
      wearers aged 19-25 inserted their lenses at least 30 min prior to the study. Each
      participant was asked to remove a contact lens from one eye (control eye,
      selected at random) upon commencement of the study, and then to remove the lens
      in the other eye (lens-wearing eye) after a 30 min washout period. IOP was
      measured immediately in both eyes using non-contact tonometry, then repeated
      every 3 min for 12 min. To determine the change in IOP due to lens removal, the
      IOP in the lens-wearing eye was compared to the control eye using paired t-tests
      at each time point. RESULTS: The IOP was significantly higher in the lens-wearing
      eye immediately following lens removal (0.7 +/- 1.0 mmHg, t(24) = 3.46, p <
      0.01), but was within baseline values at 3 min (0.2 +/- 1.0 mmHg, t(24) = 0.84, p
      = 0.41), 6 min (0.3 +/- 1.1 mmHg, t(24) = 1.39, p = 0.18), 9 min (0.3 +/- 1.2
      mmHg, t(24) = 1.14, p = 0.27) and 12 min (-0.1 +/- 0.9 mmHg, t(24) = -0.49, p =
      0.63, paired t-test). CONCLUSIONS: There was a slight statistically significant
      increase in IOP following contact lens removal, with a maximum duration of 3 min.
      Given the small magnitude of the change in IOP, and its transient nature, there
      appears to be no clinical reason to delay IOP measurements following the removal
      of modern disposable hydrogel contact lenses.

PMID- 25761582
TI  - Impact of supply problems of preservative-free glaucoma medications on patients
      and hospital staff.
AB  - PURPOSE: Glaucoma is a chronic ocular disease, which is usually managed with long
      term daily medical therapy, in the form of eye drops. Patients who are intolerant
      to preservatives in topical medicines require preservative-free versions. From
      early 2011 patients attending Moorfields Eye Hospital, London, UK, started to
      report recurring problems with the supply of the following preservative-free
      glaucoma medications: Timolol 0.25% (Timoptol 0.25%, MSD UK); Dorzolamide
      (Trusopt, MSD UK); Dorzolamide and Timolol 0.5% (Cosopt, MSD UK). This study
      investigates the impact of the supply problems of these medications at Moorfields
      Eye Hospital from a patient, administrative and clinical perspective. METHODS:
      Information was sought by interviewing both patients and hospital staff, and by a
      retrospective case note review between April 2010 and May 2013. RESULTS: Many
      hospital roles, both administrative and clinical, were involved in attempting to
      resolve the impact of the supply problems. All staff reported a considerable
      increase in their workload. At the peak of the problem, the glaucoma secretaries
      received about 150 enquiries per week. A review of 83 sets of patient notes,
      retrieved from a random sample of 125 patients, showed that 22% encountered a
      supply problem. Of these, more than one-third attended Moorfields Eye Hospital
      Accident & Emergency (A&E) for repeat supplies and 89% eventually had their
      medication changed. In telephone interviews with 39 of a random sample of 50
      patients (a subset of the 83 notes retrieved), 59% of the interviewees reported a
      supply problem. Of these, one-third attended Moorfields Eye Hospital A&E for
      repeat supplies and half eventually required an alternative medication. Some
      patients reported going to considerable lengths to obtain ongoing supplies in the
      community. CONCLUSIONS: This study shows that medication supply problems can have
      a major impact on patients and hospital services. Supply problems occur across
      many fields of medicine and with increasing frequency. The findings of this study
      highlight the importance of early communication of impending shortages between
      manufacturers and the Department of Health, as recommended in the best practice
      guidelines. In order to minimise the impact of medicine shortages on patients,
      clinicians and administrative staff, hospitals need immediate notification of
      potential supply problems and clear updates on supply resolution. In addition,
      hospitals should consider nominating an individual as a contact point for patient
      enquiries regarding medicine supply problems.

PMID- 25761583
TI  - Identification of post-gonioscopy hypotony: a simple clinical test to help
      diagnose occult cyclodialysis clefts.

PMID- 25761584
TI  - The equity profile of an enhanced optometry scheme.

PMID- 25761585
TI  - Repair of spinal cord injury by implantation of bFGF-incorporated HEMA-MOETACL
      hydrogel in rats.
AB  - There is no effective strategy for the treatment of spinal cord injury (SCI). An
      appropriate combination of hydrogel materials and neurotrophic factor therapy is
      currently thought to be a promising approach. In this study, we performed
      experiments to evaluate the synergic effect of implanting hydroxyl ethyl
      methacrylate [2-(methacryloyloxy)ethyl] trimethylammonium chloride (HEMA-MOETACL)
      hydrogel incorporated with basic fibroblast growth factor (bFGF) into the site of
      surgically induced SCI. Prior to implantation, the combined hydrogel was
      surrounded by an acellular vascular matrix. Sprague-Dawley rats underwent
      complete spinal cord transection at the T-9 level, followed by implantation of
      bFGF/HEMA-MOETACL 5 days after transection surgery. Our results showed that the
      bFGF/HEMA-MOETACL transplant provided a scaffold for the ingrowth of regenerating
      tissue eight weeks after implantation. Furthermore, this newly designed implant
      promoted both nerve tissue regeneration and functional recovery following SCI.
      These results indicate that HEMA-MOETACL hydrogel is a promising scaffold for
      intrathecal, localized and sustained delivery of bFGF to the injured spinal cord
      and provide evidence for the possibility that this approach may have clinical
      applications in the treatment of SCI. 

PMID- 25761586
TI  - Local endocytosis triggers dendritic thinning and pruning in Drosophila sensory
      neurons.
AB  - The refinement of neural circuits involves dendrite pruning, a process that
      removes inappropriate projections that are formed during development. In
      Drosophila sensory neurons, compartmentalized calcium (Ca(2+)) transients in
      dendrites act as spatiotemporal cues to trigger pruning, yet how neurons define
      the dendrites with Ca(2+) transients remains elusive. Here we report that local
      elevation of endocytic activity contributes to defining dendrites that generate
      Ca(2+) transients, triggering pruning. In vivo imaging of single dendrites
      reveals an increase of endocytosis in proximal dendrites that spatially and
      temporally correlates with dendrite thinning, an early step in pruning tightly
      coupled with compartmentalized Ca(2+) transients. Two GTPases, Rab5 and dynamin,
      are required for both the increased endocytic activity and compartmentalized
      Ca(2+) transients. Further genetic analyses suggest that local endocytosis in
      proximal dendrites functions cooperatively with global endocytosis-mediated
      protein degradation pathways to promote dendrite pruning. 

PMID- 25761587
TI  - Gonadotrophin-releasing hormone analogue or dienogest plus estradiol valerate to
      prevent pain recurrence after laparoscopic surgery for endometriosis: a multi
      center randomized trial.
AB  - OBJECTIVES: To evaluate the efficacy of dienogest + estradiol valerate (E2V) and
      gonadotrophin-releasing hormone analogue (GnRH-a) in reducing recurrence of pain
      in patients with chronic pelvic pain due to laparoscopically diagnosed and
      treated endometriosis. DESIGN: Multi-center, prospective, randomized study.
      SETTING: Three university departments of obstetrics and gynecology in Italy.
      POPULATION: Seventy-eight women who underwent laparoscopic surgery for
      endometriosis combined with chronic pelvic pain. METHODS: Post-operative
      administration of dienogest + E2V for 9 months (group 1) or GnRH-a monthly for 6
      months (group 2). MAIN OUTCOME MEASURES: A visual analogue scale was used to test
      intensity of pain before laparoscopic surgery at 3, 6 and 9 months of follow up.
      A questionnaire to investigate quality of life was administered before surgery
      and at 9 months of follow up. RESULTS: The visual analogue scale score did not
      show any significant differences between the two groups (p = 0.417). The
      questionnaire showed an increase of scores for all women compared with pre
      surgery values, demonstrating a marked improvement in quality of life and health
      related satisfaction with both treatments. No significant differences were found
      between the groups. The rate of apparent endometriosis recurrence was 10.8% in
      group 1 and 13.7% in group 2 (p = 0.962). CONCLUSION: Both therapies seemed
      equally efficacious in preventing endometriosis-related chronic pelvic pain
      recurrence in the first 9 months of follow-up.

PMID- 25761588
TI  - Coffee consumption and bladder cancer: a meta-analysis of observational studies.
AB  - Controversial results of the association between coffee consumption and bladder
      cancer (BC) risk were reported among epidemiological studies. Therefore, we
      conducted this meta-analysis to clarify the association. Relevant studies were
      identified according to the inclusion criteria. Totally, 34 case-control studies
      and 6 cohort studies were included in our meta-analysis. The overall odds ratio
      (OR) with 95% confidence interval (CI) between coffee consumption and BC risk was
      1.33 (95% CI 1.19 to 1.48). The summary ORs of BC for an increase of 1 cup of
      coffee per day were 1.05 (95% CI 1.03 to 1.06) for case-control studies and 1.03
      (95% CI 0.99 to 1.06) for cohort studies. The overall ORs for male coffee
      drinkers, female coffee drinkers and coffee drinkers of both gender were 1.31
      (95% CI: 1.08 to 1.59), 1.30 (95% CI: 0.87 to 1.96) and 1.35 (95% CI: 1.20 to
      1.51). Compared with smokers (OR = 1.24, 95% CI: 0.91 to 1.70), non-smokers had a
      higher risk (OR = 1.72, 95% CI: 1.25 to 2.35) for BC. Results of this meta
      analysis suggested that there was an increased risk between coffee consumption
      and BC. Male coffee drinkers and non-smoking coffee drinkers were more likely to
      develop BC. 

PMID- 25761589
TI  - Levator hiatal area as a risk factor for cystocele recurrence after surgery: a
      prospective study.
AB  - OBJECTIVE: To investigate whether increased levator hiatal area, measured
      preoperatively, was independently associated with anatom-ical cystocele
      recurrence 12 months after anterior colporrhaphy. DESIGN: Multicentre prospective
      cohort study. SETTING: Nine teaching hospitals in the Netherlands. POPULATION:
      Women planned for conventional anterior colporrhaphy without mesh. METHODS: Women
      underwent physical examination, translabial three-dimensional (3D) ultrasound and
      magnetic resonance imaging (MRI) prior to surgery. At 12 months after surgery the
      physical examination was repeated. MAIN OUTCOME MEASURES: Women with and without
      anatomical cystocele recurrence were compared to assess the association with
      levator hiatal area on 3D ultrasound, levator hiatal area on MRI, and potential
      confounding factors. The receiver operating characteristic (ROC) curve was
      created to quantify the discriminative ability of using levator hiatal area to
      predict anatomical cystocele recurrence. RESULTS: Of 139 included women, 76
      (54.7%) had anatomical cystocele recurrence. Preoperative stage 3 or 4 and
      increased levator hiatal area during Valsalva on ultrasound were significantly
      associated with cystocele recurrence, with odds ratios of 3.47 (95% confidence
      interval, 95% CI 1.66-7.28) and 1.06 (95% CI 1.01-1.11) respectively. The area
      under the ROC curve was 0.60 (95% CI 0.51-0.70) for levator hiatal area during
      Valsalva on ultrasound, and 0.65 (95% CI 0.55-0.71) for preoperative Pelvic Organ
      Prolapse Quantification (POP-Q) stage. CONCLUSIONS: Increased levator hiatal area
      during Valsalva on ultrasound prior to surgery and preoperative stage 3 or 4 are
      independent risk factors for anatomical cystocele recurrence after anterior
      colporrhaphy; however, increased levator hiatal area as the sole factor for
      predicting anatomical cystocele recurrence after surgery shows poor test
      characteristics.

PMID- 25761590
TI  - Transport of trans-tiliroside (kaempferol-3-beta-D-(6"-p-coumaroyl
      glucopyranoside) and related flavonoids across Caco-2 cells, as a model of
      absorption and metabolism in the small intestine.
AB  - 1. Absorption and metabolism of tiliroside (kaempferol 3-beta-D-(6"-p-coumaroyl)
      glucopyranoside) and its related compounds kaempferol, kaempferol-3-glucoside and
      p-coumaric acid were investigated in the small intestinal Caco-2 cell model.
      Apparent permeation (Papp) was determined as 0.62 * 10(-6) cm/s, 3.1 * 10(-6)
      cm/s, 0 and 22.8 * 10(-6) cm/s, respectively. 2. Mechanistic study showed that
      the transportation of tiliroside, kaempferol-3-glucoside and p-coumaric acid in
      Caco-2 model were transporter(s) involved, while transportation of kaempferol was
      solely by passive diffusion mechanism. 3. Efflux transporters, multi-drug
      resistance-associated protein-2 (MRP2), were shown to play a role in limiting the
      uptake of tiliroside. Inhibitors of MRP2, (MK571 and rifampicin) and co
      incubation with kaempferol (10 MUM), increased transfer from the apical to the
      basolateral side by three to five fold. 4. Metabolites of kaempferol-3-glucoside
      and p-coumaric acid were not detected in the current Caco-2 model, while
      tiliroside was metabolised to a limited extent, with two tiliroside mono
      glucuronides identified; and kaempferol was metabolised to a higher extent, with
      three mono-glucuronides and two mono-sulfates identified. 5. In conclusion,
      tiliroside was metabolised and transported across Caco-2 cell membrane to a
      limited extent. Transportation could be increased by applying MRP2 inhibitors or
      co-incubation with kaempferol. It is proposed that tiliroside can be absorbed by
      human; future pharmacokinetics studies are warranted in order to determine the
      usefulness of tiliroside as a bioactive agent.

PMID- 25761591
TI  - Claudin 11 inter-sertoli tight junctions in the testis of the korean soft-shelled
      turtle (Pelodiscus maackii).
AB  - Expression of claudin 11 (CLDN11), a tight junction (TJ) protein, was examined in
      the Korean soft-shelled turtle (Pelodiscus maackii) testis. Spermatogenesis began
      during the breeding season and peaked at the end of the breeding season.
      Spermiation started in summer and peaked in autumn. The deduced amino acid
      sequence of P. maackii CLDN11 was similar to those of avian and mammalian
      species. During the nonbreeding season when spermatogenesis and testosterone
      production were active, testicular Cldn11 levels were high. In the seminiferous
      epithelium, strong, wavy CLDN11 strands parallel to the basement membrane
      delaminate the spermatogonia, and early spermatocytes are in the open
      compartment. Otherwise, CLDN11 was found beneath the early spermatocytes and in
      the Sertoli cell cytoplasm. Punctate zonula occludens 1 (ZO-1) immunoreactivity
      was found within the CLDN11 strands parallel to the basement membrane or at the
      outermost periphery of the seminiferous epithelium close to the basal lamina.
      During the breeding season, when circulating testosterone levels and
      spermatogenic activity was low, testicular CLDN11 level was lower than those
      during the nonbreeding season. CLDN11 was found at apicolateral contact sites
      between adjacent Sertoli cells devoid of the postmeiotic germ cells. At this
      time, lanthanum tracer diffused to the adluminal compartment of seminiferous
      epithelium. In cultured testis tissues, testosterone propionate significantly
      increased the level of Cldn11 mRNA. In P. maackii testis, CLDN11 participates in
      the development of the blood-testis barrier (BTB), where the CLDN11 expression
      was coupled with spermatogenic activity and circulating androgen levels,
      indicating the conserved nature of TJs expressing CLDN11 at the BTB in amniotes. 

PMID- 25761592
TI  - Comparative analysis of testis transcriptomes from triploid and fertile diploid
      cyprinid fish.
AB  - The fertility of fish is a key factor in fish breeding. RNA-seq is widely used in
      high-throughput sequencing and provides a rapid method to examine the molecular
      mechanisms underlying a biological process. To probe fertility-related molecular
      mechanisms, we obtained testis transcriptomes from diploid and triploid cyprinid
      fish and tested for differentially expressed genes (DEGs) in the testis. A total
      of 6730 transcripts were differentially expressed between the triploid and
      diploid fish. In these transcripts, 2428 transcripts showed reduced expression
      and 4302 transcripts were overexpressed in triploid fish compared to the diploid
      fish. Functional analyses revealed that partial genes related to reproductive,
      developmental, and locomotion processes, and the axoneme, were differentially
      expressed in triploid fish relative to diploid fish. Pathway analysis indicated
      that variations in the gene expression levels of the "ubiquinone and other
      terpenoid-quinone biosynthesis pathway" and the "apoptotic pathway" played a
      central role in the sterility of triploid male fish. A series of genes (DNAHs,
      DNAL1, IFTs, and DNAAF1) associated with sperm flagellar assembly and motility,
      and testis-specific candidate markers (Tcte1, Tekt1, Tekt4, Spag17, Spag5,
      Spag9a, Spag1b, and Spef2), had low expression levels in the testis of triploid
      fish. We validated these DEGs in triploid fish using quantitative PCR to quantify
      expression of eight representative genes. Furthermore, 276 putative transcription
      factors, 6 chromatin remodeling factors, and 35 transcription cofactors exhibited
      differential expression in triploid compared to diploid fish. This study provides
      insight into the regulatory mechanisms causing sterility in male triploid fish. 

PMID- 25761593
TI  - Activation of the transcription factor nuclear factor-kappa B in uterine luminal
      epithelial cells by interleukin 1 Beta 2: a novel interleukin 1 expressed by the
      elongating pig conceptus.
AB  - Conceptus mortality is greatest in mammals during the peri-implantation period, a
      time when conceptuses appose and attach to the uterine surface epithelium while
      releasing proinflammatory molecules. Interleukin 1 beta (IL1B), a master
      proinflammatory cytokine, is released by the primate, rodent, and pig blastocyst
      during the peri-implantation period and is believed to be essential for
      establishment of pregnancy. The gene encoding IL1B has duplicated in the pig,
      resulting in a novel gene. Preliminary observations indicate that the novel IL1B
      is specifically expressed by pig conceptuses during the peri-implantation period.
      To verify this, IL1B was cloned from mRNA isolated from Day 12 pig conceptuses
      and compared with IL1B cloned from mRNA isolated from pig peripheral blood
      leukocytes (PBLs). The pig conceptuses, but not the PBLs, expressed a novel IL1B,
      referred to here as interleukin 1 beta 2 (IL1B2). Porcine endometrium was treated
      with recombinant porcine interleukin 1 beta 1 (IL1B1), the prototypical cytokine,
      and IL1B2 proteins. Immunohistochemistry and real-time RT-PCR were used to
      measure activation of nuclear factor-kappa B (NFKB) and NFKB-regulated
      transcripts, respectively, within the endometrium. Both IL1B1 and IL1B2 activated
      NFKB in the uterine luminal epithelium within 4 h. The NFKB activation and
      related gene expression, however, were lower in endometrium treated with IL1B2,
      suggesting that the conceptus-derived cytokine may have reduced activity within
      the uterus. In conclusion, the peri-implantation pig conceptus expresses a novel
      IL1B that can activate NFKB within the uterine surface epithelium, likely
      creating a proinflammatory microenvironment during establishment of pregnancy in
      the pig. 

PMID- 25761595
TI  - Deletion of Mylk1 in oocytes causes delayed morula-to-blastocyst transition and
      reduced fertility without affecting folliculogenesis and oocyte maturation in
      mice.
AB  - The mammalian oocyte undergoes two rounds of asymmetric cell divisions during
      meiotic maturation and fertilization. Acentric spindle positioning and cortical
      polarity are two major factors involved in asymmetric cell division, both of
      which are thought to depend on the dynamic interaction between myosin II and
      actin filaments. Myosin light chain kinase (MLCK), encoded by the Mylk1 gene,
      could directly phosphorylate and activate myosin II. To determine whether MLCK
      was required for oocyte asymmetric division, we specifically disrupted the Mylk1
      gene in oocytes by Cre-loxP conditional knockout system. We found that Mylk1
      mutant female mice showed severe subfertility. Unexpectedly, contrary to
      previously reported in vitro findings, our data showed that oocyte meiotic
      maturation including spindle organization, polarity establishment, homologous
      chromosomes separation, and polar body extrusion were not affected in
      Mylk1(fl/fl);GCre(+) females. Follicular development, ovulation, and early
      embryonic development up to compact morula occurred normally in
      Mylk1(fl/fl);GCre(+) females, but deletion of MLCK caused delayed morula-to
      blastocyst transition. More than a third of embryos were at morula stage at 3.5
      Days Postcoitum in vivo. The delayed embryos could develop further to early
      blastocyst stage in vitro on Day 4 when most control embryos reached expanded
      blastocysts. Our findings provide evidence that MLCK is linked to timely
      blastocyst formation, though it is dispensable for oocyte meiotic maturation. 

PMID- 25761594
TI  - Single-molecule analyses of fully functional fluorescent protein-tagged
      follitropin receptor reveal homodimerization and specific heterodimerization with
      lutropin receptor.
AB  - We have previously shown that the carboxyl terminus (cT) of human follicle
      stimulating hormone (FSH, follitropin) receptor (FSHR) is clipped before
      insertion into the plasma membrane. Surprisingly, several different constructs of
      FSHR fluorescent fusion proteins (FSHR-FPs) failed to traffic to the plasma
      membrane. Subsequently, we discovered that substituting the extreme cT of
      luteinizing hormone (LH) receptor (LHR) to create an FSHR-LHRcT chimera has no
      effect on FSHR functionality. Therefore, we used this approach to create an FSHR
      LHRcT-FP fusion. We found this chimeric FSHR-LHRcT-FP was expressed in HEK293
      cells at levels similar to reported values for FSHR in human granulosa cells,
      bound FSH with high affinity, and transduced FSH binding to produce cAMP.
      Quantitative fluorescence resonance energy transfer (FRET) analysis of FSHR-LHRcT
      YFP/FSHR-LHRcT-mCherry pairs revealed an average FRET efficiency of 12.9 +/- 5.7.
      Advanced methods in single-molecule analyses were applied in order to ascertain
      the oligomerization state of the FSHR-LHRcT. Fluorescence correlation
      spectroscopy coupled with photon-counting histogram analyses demonstrated that
      the FSHR-LHRcT-FP fusion protein exists as a freely diffusing homodimer in the
      plasma membrane. A central question is whether LHR could oligomerize with FSHR,
      because both receptors are coexpressed in differentiated granulosa cells. Indeed,
      FRET analysis revealed an average FRET efficiency of 14.4 +/- 7.5 when the FSHR
      LHR cT-mCherry was coexpressed with LHR-YFP. In contrast, coexpression of a 5
      HT2cVSV-YFP with FSHR-LHR cT-mCherry showed only 5.6 +/- 3.2 average FRET
      efficiency, a value indistinguishable from the detection limit using intensity
      based FRET methods. These data demonstrate that coexpression of FSHR and LHR can
      lead to heterodimerization, and we hypothesize that it is possible for this to
      occur during granulosa cell differentiation. 

PMID- 25761596
TI  - Gonadotropin-releasing hormone type II (GnRH-II) agonist regulates the motility
      of human decidual endometrial stromal cells: possible effect on embryo
      implantation and pregnancy.
AB  - Invasion of the maternal decidua by extravillous trophoblast is an important
      process for embryo implantation and placentation in humans. Motile behavior of
      decidual endometrial stromal cells has been considered of critical importance for
      embryo implantation and programming of human pregnancy. The gonadotropin
      releasing hormone (GnRH) effects in endometrium have raised concerns in
      reproduction. In the present study, we examined the action of GnRH-II agonist
      promoted motility of human decidual endometrial stromal cells and the mechanisms
      of the action, indicating the role of GnRH-II agonist in embryo implantation and
      early pregnancy. Human decidual endometrial stromal cells were isolated from the
      decidual tissue from healthy women undergoing elective pregnancy termination of a
      normal pregnancy at 6- to 12-wk gestation, after informed consent. Cell motility
      was estimated by invasion and migration assay. Zymography and immunoblot analysis
      were performed to investigate the mechanisms of the GnRH-II action. The GnRH-I
      receptor (GnRH-IR) was expressed in human decidual tissue and endometrial stromal
      cells. The GnRH-II agonist promoted cell motility. Mitogen-activated protein
      kinase inhibitors abolished GnRH-II agonist-induced cell motility and activation
      of MMP-2 and MMP-9. GnRH-II agonist-mediated cell motility was suppressed by
      knockdown of endogenous GnRH-IR, MMP (matrix metalloproteinase)-2, and MMP-9 with
      small interfering RNA and MMP inhibitors. Our study demonstrates that the GnRH-II
      agonist promoted the cell motility of human decidual endometrial stromal cells
      through the GnRH-IR and the phosphorylation of extracellular signal-regulated
      protein kinase 1/2 and JNK-dependent activation of MMP-2 and MMP-9. Our findings
      represent a new concept regarding the mechanisms of GnRH-II-promoted cell
      motility, suggesting that GnRH-II agonist has strong effects on embryo
      implantation and decidual programming of human pregnancy. 

PMID- 25761597
TI  - Dynamic Changes in Equatorial Segment Protein 1 (SPESP1) Glycosylation During
      Mouse Spermiogenesis.
AB  - ESP1/SPESP1 is a testis-specific, postmeiotic gene expressed in round spermatids
      that encodes equatorial segment protein 1, an intra-acrosomal protein found in
      the acrosomal matrix and on the luminal surface of the inner and outer acrosomal
      membranes within the equatorial segment domain of mature spermatozoa. A
      comparison of testicular protein extracts with caput, corpus, and caudal
      epididymal sperm proteins revealed striking differences in the apparent masses of
      SPESP1 isoforms. The predominant isoforms of SPESP1 in the testis were 77 and 67
      kDa, with 47-kDa forms present to a minor degree. In contrast, SPESP1 isoforms of
      47 and 43 kDa were found in caput, corpus, and caudal sperm, indicating that
      SPESP1 undergoes noticeable mass changes during spermiogenesis and/or subsequent
      transport to the epididymis. On two-dimensional (2D) SDS-PAGE, testicular SPESP1
      isoforms resolved as a train of pI values from 4.9 to 5.2. Immunoprecipitated 77
      kDa SPESP1 from testis reacted with the glycoprofile stain after one-dimensional
      and 2D gel electrophoresis, indicating that the 77-kDa testicular isoform was
      highly glycosylated. One charge variant of the 67-kDa isoform was also
      glycoprofile positive after 2D gel resolution. The 47- and 43-kDa isoforms of
      SPESP1 from epididymal sperm did not stain with glycoprofile, suggesting an
      absence of, or few, glycoprofile-sensitive glycoconjugates in epididymal SPESP1.
      Treatment of testicular extracts with a variety of glycosidases resulted in mass
      shifts in immunoreactive SPESP1, indicating that testicular SPESP1 was
      glycosylated and that terminal sialic acid, N- and O-glycans were present. A
      mixture of deglycosidase enzymes (including PNGase-F, neuraminidase, beta1-4
      galactosidase, endo-alpha-N-acetylgalactosaminidase, and beta N-acetyl
      glucosaminidase) completely eliminated the 77- and 67-kDa SPESP1 bands and
      resulted in the appearance of 75-, 60-, 55-, 50-, 47-, and 43-kDa forms,
      confirming that both the 77- and 67-kDa testicular forms of SPESP1 contain
      complex carbohydrate residues. Treatment of caudal epididymal sperm with PNGase-F
      enzymes showed a faint deglycosylated band at 30 kDa, but neuraminidase did not
      result in any molecular shift, indicating that epididymal sperm SPESP1 did not
      contain sialic acid/N-acetylglucosamine residues. These findings are consistent
      with the hypothesis that SPSPESP1 undergoes significant glycosylation in the
      testis and that the majority of these glycoconjugates are removed by the time
      sperm reach the caput epididymis. Studies of the fate of SPESP1 after the
      acrosome reaction localized SPESP1 to the equatorial segment region in both
      noncapacitated and capacitated, acrosome-reacted sperm. During capacitation,
      SPESP1 underwent proteolysis, resulting in a 27-kDa fragment. Zona-free oocytes
      incubated with recSPESP1 protein showed complementary binding sites on the
      microvillar oolemmal domain. Both recSPESP1 and anti-recSPESP1 antibody inhibited
      in vitro fertilization. 

PMID- 25761598
TI  - Age-related changes in deterministic learning from positive versus negative
      performance feedback.
AB  - Feedback-based learning declines with age. Because older adults are generally
      biased toward positive information ("positivity effect"), learning from positive
      feedback may be less impaired than learning from negative outcomes. The
      literature documents mixed results, due possibly to variability between studies
      in task design. In the current series of studies, we investigated the influence
      of feedback valence on reinforcement learning in young and older adults. We used
      nonprobabilistic learning tasks, to more systematically study the effects of
      feedback magnitude, learning of stimulus-response (S-R) versus stimulus-outcome
      (S-O) associations, and working-memory capacity. In most experiments, older
      adults benefitted more from positive than negative feedback, but only with large
      feedback magnitudes. Positivity effects were pronounced for S-O learning, whereas
      S-R learning correlated with working-memory capacity in both age groups. These
      results underline the context dependence of positivity effects in learning and
      suggest that older adults focus on high gains when these are informative for
      behavior. 

PMID- 25761599
TI  - Ethylene polymerization by the thermally unique 1-[2-(bis(4-fluoro phenyl)methyl)
      4,6-dimethylphenylimino]-2-aryliminoacenaphthylnickel precursors.
AB  - A series of 1-[2-(bis(4-fluorophenyl)methyl)-4,6-dimethylphenylimino]-2
      aryliminoacenaphthylene derivatives together with the corresponding nickel
      bromide complexes was synthesized and characterized. Representative complexes C2
      and C5 were characterized by the single-crystal X-ray diffraction, revealing a
      distorted tetrahedral geometry. Upon activation with either methylaluminoxane
      (MAO) or ethylaluminum sesquichloride (EASC), all nickel complexes exhibited high
      activities towards ethylene polymerization, producing polyethylene with a
      relatively low degree of branching and narrow polydispersity. Complex C1
      maintained good activity at elevated reaction temperatures, which indicates
      significant thermal stability of the active species.

PMID- 25761601
TI  - Brain networks governing the golf swing in professional golfers.
AB  - Golf, as with most complex motor skills, requires multiple different brain
      functions, including attention, motor planning, coordination, calculation of
      timing, and emotional control. In this study we assessed the correlation between
      swing components and brain connectivity from the cerebellum to the cerebrum. Ten
      female golf players and 10 age-matched female controls were recruited. In order
      to determine swing consistency among participants, the standard deviation (SD) of
      the mean swing speed time and the SD of the mean swing angle were assessed over
      30 swings. Functional brain connectivity was assessed by resting state functional
      MRI. Pro-golfers showed greater positive left cerebellum connectivity to the
      occipital lobe, temporal lobe, parietal lobe and both frontal lobes compared to
      controls. The SD of play scores was positively correlated with the SD of the
      impact angle. Constant swing speed and back swing angle in professional golfers
      were associated with functional connectivity (FC) between the cerebellum and
      parietal and frontal lobes. In addition, the constant impact angle in
      professional golfers was associated with improved golf scores and additional FC
      of the thalamus. 

PMID- 25761600
TI  - Alpha-lipoic acid treatment is neurorestorative and promotes functional recovery
      after stroke in rats.
AB  - The antioxidant properties of alpha-lipoic acid (aLA) correlate with its ability
      to promote neuroproliferation. However, there have been no comprehensive studies
      examining the neurorestorative effects of aLA administration after the onset of
      ischemia. The middle cerebral artery (MCA) of adult rats was occluded for 2 hours
      and then reperfused. aLA (20 mg/kg) was administered in 71 animals (aLA group)
      through the left external jugular vein immediately after reperfusion. An
      equivalent volume of vehicle was administered to 71 animals (control group).
      Functional outcome, levels of endogenous neural precursors with neurogenesis,
      glial cell activation, and brain metabolism were evaluated. Immediate aLA
      administration after reperfusion resulted in significantly reduced mortality,
      infarct size, and neurological deficit score (NDS) in the test group compared to
      the control group. Long-term functional outcomes, measured by the rotarod test,
      were markedly improved by aLA treatment. There was a significant increase in the
      number of cells expressing nestin and GFAP in the boundary zone and infarct core
      regions after aLA treatment. Furthermore, significantly more BrdU/GFAP, BrdU/DCX,
      and BrdU/NeuN double-labeled cells were observed along the boundary zone of the
      aLA group on days 7, 14, and 28 days, respectively. And brain metabolism using
      (18)F-FDG microPET imaging was markedly improved in aLA group. The effects of aLA
      was blocked by insulin receptor inhibitor, HNMPA (AM)3. These results indicate
      that immediate treatment with aLA after ischemic injury may have significant
      neurorestorative effects mediated at least partially via insulin receptor
      activation. Thus, aLA may be useful for the treatment of acute ischemic stroke. 

PMID- 25761603
TI  - Kartik Modha: Digital health pioneer.

PMID- 25761602
TI  - TLR-independent anti-inflammatory function of intestinal epithelial TRAF6
      signalling prevents DSS-induced colitis in mice.
AB  - OBJECTIVE: The gut microbiota modulates host susceptibility to intestinal
      inflammation, but the cell types and the signalling pathways orchestrating this
      bacterial regulation of intestinal homeostasis remain poorly understood. Here, we
      investigated the function of intestinal epithelial toll-like receptor (TLR)
      responses in the dextran sodium sulfate (DSS)-induced mouse model of colitis.
      DESIGN: We applied an in vivo genetic approach allowing intestinal epithelial
      cell (IEC)-specific deletion of the critical TLR signalling adaptors, MyD88
      and/or TIR-domain-containing adapter-inducing interferon-beta (TRIF), as well as
      the downstream ubiquitin ligase TRAF6 in order to reveal the IEC-intrinsic
      function of these TLR signalling molecules during DSS colitis. RESULTS: Mice
      lacking TRAF6 in IECs showed exacerbated DSS-induced inflammatory responses that
      ensued in the development of chronic colon inflammation. Antibiotic pretreatment
      abolished the increased DSS susceptibility of these mice, showing that epithelial
      TRAF6 signalling pathways prevent the gut microbiota from driving excessive
      colitis. However, in contrast to epithelial TRAF6 deletion, blocking epithelial
      TLR signalling by simultaneous deletion of MyD88 and TRIF specifically in IECs
      did not affect DSS-induced colitis severity. This in vivo functional comparison
      between TRAF6 and MyD88/TRIF deletion in IECs shows that the colitis-protecting
      effects of epithelial TRAF6 signalling are not triggered by TLRs. CONCLUSIONS:
      Intestinal epithelial TRAF6-dependent but MyD88/TRIF-independent and, thus, TLR
      independent signalling pathways are critical for preventing propagation of DSS
      induced colon inflammation by the gut microbiota. Moreover, our experiments using
      mice with dual MyD88/TRIF deletion in IECs unequivocally show that the gut
      microbiota trigger non-epithelial TLRs rather than epithelial TLRs to restrict
      DSS colitis severity.

PMID- 25761604
TI  - An FDG-PET/CT-positive lesion mimicking local recurrence of colon cancer 5 years
      after radical colectomy.
AB  - BACKGROUND: Radical resection of colorectal cancer yields satisfactory results.
      Even if the cancer recurs, long-term survival is expected through further
      surgical resection of the recurrent disease. For early detection of recurrent
      lesions, we routinely perform periodic blood tests and imaging studies, in which
      18F-fluorodeoxyglucose-glucose positron emission tomography (FDG-PET) plays an
      important role, for lesion differentiation. We encountered a case of a benign
      lesion, which had been clinically diagnosed as recurrence of resected colon
      cancer by FDG-PET/computed tomography (CT). CASE REPORT: A 69-year-old woman
      underwent radical resection of stage II sigmoid colon cancer. Five years after
      the operation, local recurrence was suspected on the basis of follow-up CT
      examination findings. Since the standardized uptake value (SUV) on FDG-PET/CT was
      13.3, we diagnosed the lesion as a postoperative local recurrence and performed
      surgical resection of the lesion. The lesion was conclusively diagnosed as benign
      fatty tissue, including a fibrovascular component, by histopathological
      examination. CONCLUSIONS: FDG-PET is a very useful technique for differentiating
      benign from malignant disease. In colorectal cancer, FDG-PET not only enables the
      differentiation of malignancy in the primary tumor, but also the confirmation of
      metastasis and postoperative recurrence. However, even if the SUV is high, as in
      the presented case, the lesion may eventually be diagnosed as benign. Therefore,
      further advances in the PET technique are expected along with the development of
      more useful modalities.

PMID- 25761605
TI  - Assessment of multidrug resistance, clonality and virulence in non-PCV-13
      Streptococcus pneumoniae serotypes in Canada, 2011-13.
AB  - OBJECTIVES: Serotype replacement in Streptococcus pneumoniae following the
      implementation of a new vaccine has been associated with the emergence of non
      vaccine serotypes as prominent causes of invasive pneumococcal disease (IPD). The
      aim of this study was to characterize specific non-PCV-13 serotypes 15A, 22F, 33F
      and 35B from IPD, isolated in Canada post-PCV-13 introduction in 2010. METHODS:
      Of 3802 IPD isolates collected from across Canada in 2011-13, 18.4% were found to
      be serotypes 15A, 22F, 33F and 35B. These 699 isolates were subjected to
      antimicrobial susceptibility testing, PFGE, MLST, molecular detection of
      pneumococcal pili and comparison with Pneumococcal Molecular Epidemiology Network
      (PMEN) clones. RESULTS: This study demonstrated clonal spread of specific STs,
      including MDR ST63 and its Sweden(15A)-25-related variants, the increasingly
      common ST433 and a variant of piliated, penicillin-non-susceptible ST558, related
      to PMEN clone Utah(35B)-24 (ST377). New STs of serotype 33F were identified.
      Several potential capsular switching events were identified within these
      serotypes. CONCLUSIONS: Non-PCV-13 serotype 22F is increasing in Canada through
      the rapid clonal expansion of ST433. Numerous new STs associated with serotype
      33F indicate the potential divergence of the serotype. Serotypes 15A and 35B in
      Canada are related to international clones of S. pneumoniae.

PMID- 25761606
TI  - Cuban embargo restrictions lifted: impact on health care?

PMID- 25761607
TI  - A general-purpose framework to simulate musculoskeletal system of human body:
      using a motion tracking approach.
AB  - Computation of muscle force patterns that produce specified movements of muscle
      actuated dynamic models is an important and challenging problem. This problem is
      an undetermined one, and then a proper optimization is required to calculate
      muscle forces. The purpose of this paper is to develop a general model for
      calculating all muscle activation and force patterns in an arbitrary human body
      movement. For this aim, the equations of a multibody system forward dynamics,
      which is considered for skeletal system of the human body model, is derived using
      Lagrange-Euler formulation. Next, muscle contraction dynamics is added to this
      model and forward dynamics of an arbitrary musculoskeletal system is obtained.
      For optimization purpose, the obtained model is used in computed muscle control
      algorithm, and a closed-loop system for tracking desired motions is derived.
      Finally, a popular sport exercise, biceps curl, is simulated by using this
      algorithm and the validity of the obtained results is evaluated via EMG signals.

PMID- 25761608
TI  - The illusion of client-centred practice.
AB  - AIM: A critical analysis of occupational therapy practice in the corporate health
      care culture in a free market economy was undertaken to demonstrate incongruence
      with the profession's philosophical basis and espoused commitment to client
      centred practice. FINDINGS: The current practice of occupational therapy in the
      reimbursement-driven practice arena in the United States is incongruent with the
      profession's espoused philosophy and values of client-centred practice.
      Occupational therapy differentiates itself from medicine's expert model aimed at
      curing disease and remediating impairment, by its claim to client-centred
      practice focused on restoring health through occupational enablement. Practice
      focused on impairment and function is at odds with the profession's core tenet,
      occupation, and minimizes the lasting impact of interventions on health and well
      being. The profession cannot unleash the therapeutic power of human occupation in
      settings where body systems and body functions are not occupation-ready at the
      requisite levels for occupational participation. CONCLUSION: Client-centred
      practice is best embodied by occupation-focused interventions in the natural
      environment of everyday living. Providing services that are impairment-focused in
      unfamiliar settings is not a good fit for client-centred practice, which is the
      unique, authentic, and sustainable orientation for the profession.

PMID- 25761611
TI  - Linifanib--a multi-targeted receptor tyrosine kinase inhibitor and a low
      molecular weight gelator.
AB  - In this study we demonstrate that linifanib, a multi-targeted receptor tyrosine
      kinase inhibitor, with a key urea containing pharmacophore, self-assembles into a
      hydrogel in the presence of low amounts of solvent. We demonstrate the role of
      the urea functional group and that of fluorine substitution on the adjacent
      aromatic ring in promoting self-assembly. We have also shown that linifanib has
      superior mechanical strength to two structurally related analogues and hence
      increased potential for localisation at an injection site for drug delivery
      applications. 

PMID- 25761610
TI  - MicroRNA-155 may be involved in the pathogenesis of atopic dermatitis by
      modulating the differentiation and function of T helper type 17 (Th17) cells.
AB  - Our aims were to identify the differential expression of microRNA (miR)-155, as
      well as to explore the possible regulatory effects of miR-155 on the
      differentiation and function of T helper type 17 (Th17) cells in atopic
      dermatitis (AD). The Th17 cell percentage and expression levels of miR-155,
      retinoic acid-related orphan receptor (ROR)gammat, interleukin (IL)-17 and
      suppressor of cytokine signalling-1 (SOCS1) in peripheral CD4(+) T cells, plasma
      and skin specimens were detected and compared in AD patients and healthy
      subjects. A miR-155 mimic and an inhibitor were transfected separately into AD
      CD4(+) T cells to confirm the in-vivo data. The Th17 cell percentage, miR-155
      expression, RORgammat mRNA expression, IL-17 mRNA expression and plasma
      concentration were increased significantly in AD patients compared with healthy
      subjects. Conversely, SOCS1 mRNA expression and plasma concentration were
      decreased significantly. Similar results were detected in cultured CD4(+) T cells
      transfected with the miR-155 mimic compared with a miR-155 inhibitor or a
      negative control. Additionally, there was a sequential decrease in miR-155
      expression, as well as RORgammat and IL-17 mRNA expression, but an increase in
      SOCS1 mRNA expression, from AD lesional skin and perilesional skin to normal
      skin. Positive correlations were found between miR-155 expression and AD
      severity, Th17 cell percentage, RORgammat mRNA expression and IL-17 mRNA
      expression and plasma concentration, while negative correlations were observed
      between miR-155 expression and SOCS1 mRNA expression and plasma concentration in
      AD peripheral circulation and skin lesions. In conclusion, miR-155 is over
      expressed and may be involved in AD pathogenesis by modulating the
      differentiation and function of Th17 cells. 

PMID- 25761612
TI  - An outbreak of human metapneumovirus in a rehabilitation center for alcoholics in
      Tampere, Finland.
AB  - Reports of respiratory tract infections in a rehabilitation center for alcoholics
      triggered the epidemiological investigations in Tampere, Finland. Twenty-nine out
      of 40 residents (attack rate 73%) and four members of staff fulfilled the case
      criteria: cough; worsening of dyspnea; or rhinitis with or without fever. Ten
      cases were hospitalized, one needed treatment in the intensive care unit. All
      cases recovered. Serum hMPV antibody titer was high (10 240 or more) in 20 (69%)
      of the 29 tested cases and the difference was significant when compared with the
      titer measured from the voluntary laboratory personnel (n = 14, p < 0.001). The
      titers were rising in three out of the five cases from whom coupled samples could
      be obtained. Rt-PCR for hMPV was positive in three out of the eight tested cases.
      No other causative agent for the outbreak was detected. The outcome of hMPV
      infection among institutionalized smoking alcoholics was good with no mortality. 

PMID- 25761613
TI  - Predictors of positive or negative legionella urinary antigen test in community
      acquired pneumonia.
AB  - BACKGROUND: Legionella pneumonia remains a diagnostic challenge. The legionella
      urinary antigen test (LUT) primarily detects Legionella pneumophila serogroup 1,
      accounting for 64% of Danish cases, and is often the only legionella test
      performed. We aimed to identify variables predictive of a positive or negative
      test result and to explore how the LUT was used in clinical practice. METHODS:
      The study was an audit-based cohort study. LUT-positive patients were compared
      with three randomly selected age- and gender-matched LUT-negative referent
      patients admitted at a Danish university hospital during 2003-2013. Data were
      extracted from charts and databases. Positive and negative likelihood ratios (LR+
      and LR-) were calculated. For CURB-65 and sepsis, sensitivity analyses were made
      due to incomplete data. RESULTS: In all, 25 cases were compared with 75
      referents. Factors associated with LUT positivity included recent travel outside
      Scandinavia (LR + 5.3), Na(+) < 130 mEq/L (LR + 4.3), confusion (LR + 4.2), C
      reactive protein (CRP) > 200 mg/L (LR + 3.5), temperature > 39  degrees C (LR +
      3.5), and CURB-65 score >= 3 (LR + 3.0-15.0, depending on the model). Decreasing
      the likelihood of LUT positivity were CRP < 200 mg/L (LR- 0.1), absence of sepsis
      (LR- 0.1-0.2, depending on the model), absence of tachycardia (heart rate < 90)
      (LR- 0.2) and normal pulmonary auscultation (LR- 0.3). Additional legionella
      tests were performed in 60% of the cases and 13% of the referents. CONCLUSION:
      Classical features of severe pneumonia are associated with a positive LUT. The
      LUT is often used inappropriately and should be accompanied by PCR analysis.

PMID- 25761615
TI  - Amicitiae Sacrum - voices from the past.

PMID- 25761614
TI  - Structure-guided design and optimization of dipeptidyl inhibitors of norovirus
      3CL protease. Structure-activity relationships and biochemical, X-ray
      crystallographic, cell-based, and in vivo studies.
AB  - Norovirus infection constitutes the primary cause of acute viral gastroenteritis.
      There are currently no vaccines or norovirus-specific antiviral therapeutics
      available for the management of norovirus infection. Norovirus 3C-like protease
      is essential for viral replication, consequently, inhibition of this enzyme is a
      fruitful avenue of investigation that may lead to the emergence of antinorovirus
      therapeutics. We describe herein the optimization of dipeptidyl inhibitors of
      norovirus 3C-like protease using iterative SAR, X-ray crystallographic, and
      enzyme and cell-based studies. We also demonstrate herein in vivo efficacy of an
      inhibitor using the murine model of norovirus infection. 

PMID- 25761616
TI  - Examination of the properties of IMRT and VMAT beams and evaluation against pre
      treatment quality assurance results.
AB  - This study aimed to provide a detailed evaluation and comparison of a range of
      modulated beam evaluation metrics, in terms of their correlation with QA testing
      results and their variation between treatment sites, for a large number of
      treatments. Ten metrics including the modulation index (MI), fluence map
      complexity, modulation complexity score (MCS), mean aperture displacement (MAD)
      and small aperture score (SAS) were evaluated for 546 beams from 122 intensity
      modulated radiotherapy (IMRT) and volumetric modulated arc therapy (VMAT)
      treatment plans targeting the anus, rectum, endometrium, brain, head and neck and
      prostate. The calculated sets of metrics were evaluated in terms of their
      relationships to each other and their correlation with the results of electronic
      portal imaging based quality assurance (QA) evaluations of the treatment beams.
      Evaluation of the MI, MAD and SAS suggested that beams used in treatments of the
      anus, rectum, head and neck were more complex than the prostate and brain
      treatment beams. Seven of the ten beam complexity metrics were found to be
      strongly correlated with the results from QA testing of the IMRT beams (p <
      0.00008). For example, values of SAS (with multileaf collimator apertures
      narrower than 10 mm defined as 'small') less than 0.2 also identified QA passing
      IMRT beams with 100% specificity. However, few of the metrics are correlated with
      the results from QA testing of the VMAT beams, whether they were evaluated as
      whole 360 degrees  arcs or as 60 degrees  sub-arcs. Select evaluation of beam
      complexity metrics (at least MI, MCS and SAS) is therefore recommended, as an
      intermediate step in the IMRT QA chain. Such evaluation may also be useful as a
      means of periodically reviewing VMAT planning or optimiser performance.

PMID- 25761617
TI  - Clinical utility of screening for CALR gene exon 9 mutations in patients with
      splanchnic venous thrombosis.

PMID- 25761618
TI  - Tumor necrosis factor alpha stimulates p62 accumulation and enhances proteasome
      activity independently of ROS.
AB  - Circulating TNF-alpha levels are elevated in a wide variety of cardiovascular
      pathologies including congestive heart failure (CHF). This cytokine is one of the
      leading mediators of the immune inflammatory response with widespread biological
      functions regulated by membrane receptors. The pathophysiological implication of
      the downstream effects of activating the TNF-alpha system in CHF appears to
      depend on its direct effects on the heart and endothelium. Evidence supporting
      the notion that circulating TNF-alpha promotes protein breakdown was initially
      obtained from studies utilizing transgenic animals overexpressing TNF-alpha,
      animals with experimental diseases that augment TNF-alpha and in animals treated
      with exogenous TNF-alpha. It was then demonstrated that TNF-alpha acts directly
      on cultured myotubes to stimulate catabolism; however, whether the effects are
      the same in the heart remains poorly understood. The present study shows that TNF
      alpha treatment induces autophagy, but clearance through this pathway appears
      obstructed and, consequently, results in increased protein ubiquitination.
      Furthermore, prolonged TNF-alpha treatment enhanced E3 ubiquitin ligase
      expression but reduced activity of the proteasome. These results suggest that TNF
      alpha induces sarcomeric dysfunction and remodeling by disrupting autophagy and
      elevating the degradation of myofibrillar proteins. Therefore, myocardial
      remodeling, as a consequence to reduced contractile proteins, contributes to
      contractile dysfunction, a symptom often observed in the end stages of CHF. 

PMID- 25761619
TI  - Missed opportunities: young adults with hypertension and lifestyle counseling in
      clinical practice.

PMID- 25761620
TI  - Capsule Commentary on Kobayashi et al., Cognitive Function and Health Literacy
      Decline in a Cohort of Aging English Adults.

PMID- 25761621
TI  - Effects of feedstock carbon to nitrogen ratio and organic loading on foaming
      potential in mesophilic food waste anaerobic digestion.
AB  - Foaming problem which occurred occasionally during food waste (FW) anaerobic
      digestion (AD) was investigated with the Malaysian FW by stepwise increase in
      organic loading (OL) from 0.5 to 7.5 g VS/L. The FW feedstock with carbon to
      nitrogen (C/N) ratio of 17 was upgraded to C/N ratio of 26 and 30 by mixing with
      other wastes. The digestion which was carried out at 37  degrees C in 1-L batch
      reactors showed that foam formation initiated at OL of 1.5 g VS/L and was further
      enhanced as OL of feedstock was increased. The digestion foaming reached its
      maximum at OL of 5.5 g VS/L and did not increase further even when OL was
      increased to 7.5 g VS/Ld. Increase in the C/N ratio of feedstock significantly
      enhanced the microbial degradation activity, leading to better removal of foam
      causing intermediates and reduced foaming in the reactor by up to 60%.

PMID- 25761609
TI  - International Union of Basic and Clinical Pharmacology. XCV. Recent advances in
      the understanding of the pharmacology and biological roles of relaxin family
      peptide receptors 1-4, the receptors for relaxin family peptides.
AB  - Relaxin, insulin-like peptide 3 (INSL3), relaxin-3, and INSL5 are the cognate
      ligands for the relaxin family peptide (RXFP) receptors 1-4, respectively. RXFP1
      activates pleiotropic signaling pathways including the signalosome protein
      complex that facilitates high-sensitivity signaling; coupling to Galpha(s),
      Galpha(i), and Galpha(o) proteins; interaction with glucocorticoid receptors; and
      the formation of hetero-oligomers with distinctive pharmacological properties. In
      addition to relaxin-related ligands, RXFP1 is activated by Clq-tumor necrosis
      factor-related protein 8 and by small-molecular-weight agonists, such as ML290 [2
      isopropoxy-N-(2-(3-(trifluoromethylsulfonyl)phenylcarbamoyl)phenyl)benzamide],
      that act allosterically. RXFP2 activates only the Galpha(s)- and Galpha(o)
      coupled pathways. Relaxin-3 is primarily a neuropeptide, and its cognate receptor
      RXFP3 is a target for the treatment of depression, anxiety, and autism. A variety
      of peptide agonists, antagonists, biased agonists, and an allosteric modulator
      target RXFP3. Both RXFP3 and the related RXFP4 couple to Galpha(i)/Galpha(o)
      proteins. INSL5 has the properties of an incretin; it is secreted from the gut
      and is orexigenic. The expression of RXFP4 in gut, adipose tissue, and beta
      islets together with compromised glucose tolerance in INSL5 or RXFP4 knockout
      mice suggests a metabolic role. This review focuses on the many advances in our
      understanding of RXFP receptors in the last 5 years, their signal transduction
      mechanisms, the development of novel compounds that target RXFP1-4, the
      challenges facing the field, and current prospects for new therapeutics.

PMID- 25761622
TI  - In-vitro nanodiagnostic platform through nanoparticles and DNA-RNA
      nanotechnology.
AB  - Nanocomposites containing nanoparticles or nanostructured domains exhibit an even
      higher degree of material complexity that leads to an extremely high variability
      of nanostructured materials. This review introduces analytical concepts and
      techniques for nanomaterials and derives recommendations for a qualified
      selection of characterization techniques for specific types of samples, and
      focuses the characterization of nanoparticles and their agglomerates or
      aggregates. In addition, DNA nanotechnology and the more recent newcomer RNA
      nanotechnology have achieved almost an advanced status among nanotechnology
      researchers  therefore, the core features, potential, and significant challenges
      of DNA nanotechnology are also highlighted as a new discipline. Moreover,
      nanobiochips made by nanomaterials are rapidly emerging as a new paradigm in the
      area of large-scale biochemical analysis. The use of nanoscale components enables
      higher precision in diagnostics while considerably reducing the cost of the
      platform that leads this review to explore the use of nanoparticles,
      nanomaterials, and other bionanotechnologies for its application to
      nanodiagnostics in-vitro.

PMID- 25761623
TI  - A giant market and a powerful metabolism: L-lysine provided by Corynebacterium
      glutamicum.
AB  - L-lysine is made in an exceptional large quantity of currently 2,200,000
      tons/year and belongs therefore to one of the leading biotechnological products.
      Production is done almost exclusively with mutants of Corynebacterium glutamicum.
      The increasing L-lysine market forces companies to improve the production process
      fostering also a deeper understanding of the microbial physiology of C.
      glutamicum. Current major challenges are the identification of ancillary
      mutations not intuitively related with product increase. This review gives
      insights on how cellular characteristics enable to push the carbon flux in
      metabolism towards its theoretical maximum, and this example may also serve as a
      guide to achieve and increase the formation of other products of interest in
      microbial biotechnology.

PMID- 25761624
TI  - Antimicrobial lubricant formulations containing poly(hydroxybenzene)-trimethoprim
      conjugates synthesized by tyrosinase.
AB  - Poly(hydroxybenzene)-trimethoprim conjugates were prepared using methylparaben as
      substrate of the oxidative enzyme tyrosinase. MALDI-TOF MS analysis showed that
      the enzymatic oxidation of methylparaben alone leads to the poly(hydroxybenzene)
      formation. In the presence of trimethoprim, the methylparaben tyrosinase
      oxidation leads poly(hydroxybenzene)-trimethoprim conjugates. All of these
      compounds were incorporated into lubricant hydroxyethyl cellulose/glycerol
      mixtures. Poly(hydroxybenzene)-trimethoprim conjugates were the most effective
      phenolic structures against the bacterial growth reducing by 96 and 97% of
      Escherichia coli and Staphylococcus epidermidis suspensions, respectively (after
      24 h). A novel enzymatic strategy to produce antimicrobial poly(hydroxybenzene)
      antibiotic conjugates is proposed here for a wide range of applications on the
      biomedical field.

PMID- 25761625
TI  - Essential oils and distilled straws of lavender and lavandin: a review of current
      use and potential application in white biotechnology.
AB  - The Lavandula genus, which includes lavender (Lavandula angustifolia) and
      lavandin (L. angustifolia * Lavandula latifolia), is cultivated worldwide for its
      essential oils, which find applications in perfumes, cosmetics, food processing
      and, more recently, in aromatherapy products. The chemical composition of
      lavender and lavandin essential oils, usually produced by steam distillation from
      the flowering stems, is characterized by the presence of terpenes (e.g. linalool
      and linalyl acetate) and terpenoids (e.g. 1,8-cineole), which are mainly
      responsible for their characteristic flavour and their biological and therapeutic
      properties. Lavender and lavandin distilled straws, the by-products of oil
      extraction, were traditionally used for soil replenishment or converted to a fuel
      source. They are mineral- and carbon-rich plant residues and, therefore, a cheap,
      readily available source of valuable substances of industrial interest,
      especially aroma and antioxidants (e.g. terpenoids, lactones and phenolic
      compounds including coumarin, herniarin, alpha-bisabolol, rosmarinic and
      chlorogenic acids). Accordingly, recent studies have emphasized the possible uses
      of lavender and lavandin straws in fermentative or enzymatic processes involving
      various microorganisms, especially filamentous fungi, for the production of
      antimicrobials, antioxidants and other bioproducts with pharmaceutical and
      cosmetic activities, opening up new challenging perspectives in white
      biotechnology applications.

PMID- 25761626
TI  - Catalases as biocatalysts in technical applications: current state and
      perspectives.
AB  - Catalases represent a class of enzymes which has found its place among
      industrially relevant biocatalysts due to their exceptional catalytic rate and
      high stability. Textile bleaching prior to the dyeing process is the main
      application and has been performed on a large scale for the past few decades.
      Their limited substrate scope has not prevented the development of various other
      catalase-based applications. Newly developed approaches continue to exploit their
      excellent catalytic potential to degrade hydrogen peroxide while (per)oxidase
      activity of catalases is opening a new range of possibilities as well. This
      review provides an overview of applications that involve heme-containing
      catalases that have been demonstrated in recent years. 

PMID- 25761627
TI  - Synthesis and swelling peculiarities of new hydrogels based on the macromolecular
      reaction of anhydride copolymers with gamma-aminopropyltriethoxysilane.
AB  - This work describes the synthesis and macromolecular reactions of maleic
      anhydride (MA)-acrylamide (AAm) binary and MA-vinyl acetate (VA)- AAm ternary
      reactive copolymers with gamma-aminopropyltriethoxysilane (APTS) as a
      polyfunctional crosslinker. Swelling parameters such as the start-time of the
      hydrogel-formation, initial rate of swelling, swelling rate constant, equilibrium
      swelling, and equilibrium water content (EWC) are determined for
      polymers/APTS/water systems with certain copolymer/crosslinker ratios (1.4/1 and
      9/1). The formation of a hyperbranched network structure by the fragmentation of
      the side-chain reactive groups in the systems studied has also been confirmed by
      the Fourier Transform Infrared (FTIR) method. 

PMID- 25761628
TI  - Physicochemical properties of polymers: An important system to overcome the cell
      barriers in gene transfection.
AB  - Delivery of the macromolecules including DNA, miRNA, and antisense
      oligonucleotides is typically mediated by carriers due to the large size and
      negative charge. Different physical (e.g., gene gun or electroporation), and
      chemical (e.g., cationic polymer or lipid) vectors have been already used to
      improve the efficiency of gene transfer. Polymer-based DNA delivery systems have
      attracted special interest, in particular via intravenous injection with many
      intra- and extracellular barriers. The recent progress has shown that stimuli
      responsive polymers entitled as multifunctional nucleic acid vehicles can act to
      target specific cells. These nonviral carriers are classified by the type of
      stimulus including reduction potential, pH, and temperature. Generally, the
      physicochemical characterization of DNA-polymer complexes is critical to enhance
      the transfection potency via protection of DNA from nuclease digestion, endosomal
      escape, and nuclear localization. The successful clinical applications will
      depend on an exact insight of barriers in gene delivery and development of
      carriers overcoming these barriers. Consequently, improvement of novel cationic
      polymers with low toxicity and effective for biomedical use has attracted a great
      attention in gene therapy. This article summarizes the main physicochemical and
      biological properties of polyplexes describing their gene transfection behavior,
      in vitro and in vivo. In this line, the relative efficiencies of various cationic
      polymers are compared.

PMID- 25761629
TI  - Origin of effects of additive solvent on film-morphology in solution-processed
      nonfullerene solar cells.
AB  - In this paper, we report an efficient nonfullerene solar cell based on small
      molecules of p-DTS(FBTTh2)2 and bis-PDI-T. Characterization data indicate that
      the nature of the acceptor aggregate is a key factor that affects the
      photocurrent. There is a good relationship between the short-circuit current
      density (J(SC)) and the phase size of the acceptor-rich domains. The phase size
      of the acceptor-rich domains is tuned by both the additive types and additive
      content. As the kind of additive goes from 1-chloronaphthalene (CN) to 1,8
      octanedithiol (ODT) and 1,8-diiodooctane (DIO), by this order the solubility of
      the acceptor in the additive is down, the phase size significantly decreases from
      over 400 nm down to 30 nm. Also, the acceptor's domain size decreases from 80 to
      30 nm as the DIO content ([DIO]) is down from 1% to 0.15%. Following this trend,
      less DIO remains in the wet film as residue after the host chloroform evaporates,
      and thus less acceptor can be dissolved in the residue DIO. This decreasing of
      DIO content acts on the film-morphology similarly as the additive changes down to
      the one having a lower solubility. Accordingly, our results indicate that it is
      the dissolved amount of the organic component in the residue additive solvent of
      the wet film that plays a role in turning the phase size. The efficiency from
      this small molecule system is significantly raised from 0.02% up to 3.7% by
      selecting the additive type and fine-tuning the additive content.

PMID- 25761630
TI  - The adductor tubercle: an important landmark to determine the joint line level in
      revision total knee arthroplasty.
AB  - PURPOSE: The restoration of the physiological femoro-tibial joint line (JL) is
      important to obtain a good outcome in revision total knee arthroplasty (RTKA).
      However, its assessment is challenging. The ratio of the distance between the
      adductor tubercle (AT) JL (ATJL) and the trans-epicondylar femoral width (FW) was
      proposed as a reliable method. The purpose of this study was to check whether
      this ratio is a reliable tool to restore the prosthetic JL height in challenging
      prosthetic revision cases. METHODS: Twenty-one patients (mean age 65.8 years)
      were recruited. During surgery, FW was measured and ATJL distance was calculated
      using 0.53 (SD 0.03) as the ratio. After implant positioning, the obtained ATJL
      line was measured to verify the accuracy of the surgical procedure. Thirteen
      patients presented a healthy contralateral knee: a comparative radiograph
      examination was performed to verify the appropriateness of the restored JL
      height. RESULTS: The intra-operatively calculated ATJL was not significantly
      different with respect to the measured ATJL obtained after prosthetic component
      implantation. The comparative analysis between the restored JL and the JL of the
      contralateral not operated knee was also not statistically significant, thus
      confirming the appropriateness of the restored JL height. CONCLUSIONS: This study
      shows that the method which uses an AT to JL distance/FW ratio to determine the
      JL level, previously applied in primary TKA, is valid when using intra
      operatively acquired measurements in RTKA. This is clinically relevant since it
      represents a reliable tool which helps surgeons to restore the JL level in
      challenging prosthetic revision cases. LEVEL OF EVIDENCE: Case series, Level IV.

PMID- 25761631
TI  - Psychosocial work factors in new or recurrent injuries among hospital workers: a
      prospective study.
AB  - PURPOSE: Accumulating evidence suggests an important role for psychosocial work
      factors in injury, but little is known about the interaction between psychosocial
      factors and previous injury experience on subsequent injury risk. We examined the
      relationships between psychosocial work factors and new or recurrent injury among
      hospital workers. METHODS: We studied 492 hospital workers including 116 cases
      with baseline injury and 376 injury-free referents at baseline over follow-up.
      Job strain, total support, effort-reward imbalance, overcommitment, and
      musculoskeletal injury at baseline were examined in logistic regression models as
      predictors of new or recurrent injury experienced during a 2-year follow-up
      period. RESULTS: The overall cumulative incidence of injury over follow-up was
      35.6 % (51.7 % for re-injury among baseline injury cases; 30.6 % for new injury
      among referents). Significantly increased risks with baseline job strain (OR
      1.26; 95 % CI 1.02-1.55) and effort-reward imbalance (OR 1.42; 95 % CI 1.12-1.81)
      were observed for injury only among the referents. Overcommitment was associated
      with increased risk of injury only among the cases (OR 1.58; 95 % CI 1.05-2.39).
      CONCLUSIONS: The effects of psychosocial work factors on new or recurrent injury
      risk appear to differ by previous injury experience, suggesting the need for
      differing preventive strategies in hospital workers.

PMID- 25761632
TI  - Gender differences in psychosocial work factors, work-personal life interface,
      and well-being among Swedish managers and non-managers.
AB  - PURPOSE: To explore differences in psychosocial work factors, work-personal life
      interface, and well-being between managers and non-managers, female and male
      managers, and managers in the public and private sectors. METHODS: Data were
      drawn from the Swedish Longitudinal Occupational Survey of Health (SLOSH) 2010,
      including 602 female managers, 4174 female non-managers, 906 male managers, and
      2832 male non-managers. Psychosocial work factors, work-personal life interface,
      satisfaction, and well-being were investigated among non-managers and managers
      and male and female managers, using logistic regression analyses adjusted for
      age, educational level, staff category, and labour market sector. RESULTS: Both
      female and male managers reported high job demands and interference between work
      and personal life, but also high influence, high satisfaction with work and life,
      and low amount of sickness absence more often than non-managers of the same sex.
      However, female managers reported high quantitative and emotional demands, low
      influence, and work-personal life interference more frequently than male
      managers. More psychosocial work stressors were also reported in the public
      sector, where many women work. Male managers more often reported conflicts with
      superiors, lack of support, and personal life-work interference. Female managers
      reported poor well-being to a greater extent than male managers, but were more
      satisfied with their lives. CONCLUSION: Lack of motivation due to limited
      increase in satisfaction and organisational benefits is not likely to hinder
      women from taking on managerial roles. Managerial women's higher overall demands,
      lower influence at work, and poorer well-being relative to men's could hinder
      female managers from reaching higher organisational levels.

PMID- 25761633
TI  - Prolonged starvation drives reversible sequestration of lipid biosynthetic
      enzymes and organelle reorganization in Saccharomyces cerevisiae.
AB  - Cells adapt to changing nutrient availability by modulating a variety of
      processes, including the spatial sequestration of enzymes, the physiological
      significance of which remains controversial. These enzyme deposits are claimed to
      represent aggregates of misfolded proteins, protein storage, or complexes with
      superior enzymatic activity. We monitored spatial distribution of lipid
      biosynthetic enzymes upon glucose depletion in Saccharomyces cerevisiae. Several
      different cytosolic-, endoplasmic reticulum-, and mitochondria-localized lipid
      biosynthetic enzymes sequester into distinct foci. Using the key enzyme fatty
      acid synthetase (FAS) as a model, we show that FAS foci represent active enzyme
      assemblies. Upon starvation, phospholipid synthesis remains active, although with
      some alterations, implying that other foci-forming lipid biosynthetic enzymes
      might retain activity as well. Thus sequestration may restrict enzymes' access to
      one another and their substrates, modulating metabolic flux. Enzyme
      sequestrations coincide with reversible drastic mitochondrial reorganization and
      concomitant loss of endoplasmic reticulum-mitochondria encounter structures and
      vacuole and mitochondria patch organelle contact sites that are reflected in
      qualitative and quantitative changes in phospholipid profiles. This highlights a
      novel mechanism that regulates lipid homeostasis without profoundly affecting the
      activity status of involved enzymes such that, upon entry into favorable growth
      conditions, cells can quickly alter lipid flux by relocalizing their enzymes. 

PMID- 25761634
TI  - ER network formation and membrane fusion by atlastin1/SPG3A disease variants.
AB  - At least 38 distinct missense mutations in the neuronal atlastin1/SPG3A GTPase
      are implicated in an autosomal dominant form of hereditary spastic paraplegia
      (HSP), a motor-neurological disorder manifested by lower limb weakness and
      spasticity and length-dependent axonopathy of corticospinal motor neurons.
      Because the atlastin GTPase is sufficient to catalyze membrane fusion and
      required to form the ER network, at least in nonneuronal cells, it is logically
      assumed that defects in ER membrane morphogenesis due to impaired fusion activity
      are the primary drivers of SPG3A-associated HSP. Here we analyzed a subset of
      established atlastin1/SPG3A disease variants using cell-based assays for atlastin
      mediated ER network formation and biochemical assays for atlastin-catalyzed GTP
      hydrolysis, dimer formation, and membrane fusion. As anticipated, some variants
      exhibited clear deficits. Surprisingly however, at least two disease variants,
      one of which represents that most frequently identified in SPG3A HSP patients,
      displayed wild-type levels of activity in all assays. The same variants were also
      capable of co-redistributing ER-localized REEP1, a recently identified function
      of atlastins that requires its catalytic activity. Taken together, these findings
      indicate that a deficit in the membrane fusion activity of atlastin1 may be a key
      contributor, but is not required, for HSP causation. 

PMID- 25761635
TI  - Lower-limb exoskeletons for individuals with chronic spinal cord injury: findings
      from a feasibility study.
AB  - OBJECTIVE: To assess the feasibility of conducting a well-powered trial
      evaluating the neurological and functional effects of using an exoskeleton in
      individuals with chronic spinal cord injury. DESIGN: A longitudinal, prospective,
      self-controlled feasibility study. SETTING: Specialist Spinal Cord Injuries
      Centre, UK; 8 months during 2013-2014. SUBJECTS: Individuals with chronic motor
      complete or incomplete spinal cord injury. INTERVENTIONS: Enrolled subjects were
      assigned to 20 exoskeleton (ReWalkTM, Argo Medical Technologies Ltd, Yokneam
      Ilit, Israel) training sessions over a 10-week training period. MAIN MEASURES:
      Feasibility measures, clinical and mobility outcome measures and measures
      appraising subjects' disability and attitude towards assistive technology were
      assessed before, during and after the study. Descriptive statistics were applied.
      RESULTS: Out of 60 candidates, ten (17%) were enrolled and five (8%) completed
      the training programme. Primary reasons for not enrolling were ineligibility (n =
      24, 40%) and limited interest to engage in a 10-week training programme (n = 16,
      27%). Five out of ten enrolled subjects experienced grade I/II skin aberrations.
      While walking speeds were higher and walking distances were longer in all
      exoskeleton users when compared with non-use, the exoskeleton did generally not
      meet subjects' high expectations in terms of perceived benefits. CONCLUSIONS: The
      conduct of a controlled trial evaluating the benefits of using exoskeletons that
      require a lengthy user-commitment to training of individuals with chronic motor
      complete or incomplete spinal cord injury comes with considerable feasibility
      challenges. Vigilance is required for preventing and detecting medical
      complications in spinal cord injury exoskeleton users.

PMID- 25761636
TI  - One-step synthesis of Si@C nanoparticles by laser pyrolysis: high-capacity anode
      material for lithium-ion batteries.
AB  - Carbon-covered silicon nanoparticles (Si@C) were synthesized for the first time
      by a one-step continuous process in a novel two stages laser pyrolysis reactor.
      Crystallized silicon cores formed in a first stage were covered in the second
      stage by a continuous shell mainly consisting in low organized sp(2) carbon. At
      the Si/C interface silicon carbide is absent. Moreover, the presence of silicon
      oxide is reduced compared to materials synthesized in several steps, allowing the
      use of such material as promising anode material in lithium-ion batteries (LIB).
      Auger Electron Spectroscopy (AES) analysis of the samples at both SiKLL and SiLVV
      edges proved the uniformity of the carbon coating. Cyclic voltammetry was used to
      compare the stability of Si and Si@C active materials. In half-cell
      configuration, Si@C exhibits a high and stable capacity of 2400 mAh g(-1) at C/10
      and up to 500 mAh g(-1) over 500 cycles at 2C. The retention of the capacity is
      attributed to the protective effect of the carbon shell, which avoids direct
      contact between the silicon surface and the electrolyte. 

PMID- 25761637
TI  - Frequency-Dependent Gating of Hippocampal-Neocortical Interactions.
AB  - How and where hippocampal-neocortical interactions required for memory formation
      take place is a major issue of current research. Using a combined in vivo
      functional magnetic resonance imaging/electrophysiology approach, we have
      investigated whether specific frequencies of CA3 neuronal activation, inducing
      different forms of short-term plasticity at CA1 synapses, contribute to
      differential activity propagation in brain-wide networks connected to the
      hippocampus. We report that localized activation of CA3 neurons in dorsal
      hippocampus produced activity propagation within the hippocampal formation,
      including the subiculum and entorhinal cortex, which increased monotonically with
      frequency to a maximum at 20-40 Hz. However, robust extrahippocampal propagation
      was seen specifically at theta-beta frequencies (10-20 Hz), reaching a network of
      midline neocortical and mesolimbic structures. Activation in those regions
      correlated with a frequency-dependent facilitation of spiking activity recorded
      in CA1. These results provide a mechanistic link between the dynamic properties
      of short-term plasticity in the efferent synapses of CA3 neurons in CA1 and
      activity propagation in brain-wide networks, and identify polysynaptic
      information channels segregated in the frequency domain. 

PMID- 25761638
TI  - Synaptic Conductance Estimates of the Connection Between Local Inhibitor
      Interneurons and Pyramidal Neurons in Layer 2/3 of a Cortical Column.
AB  - Stimulation of a principal whisker yields sparse action potential (AP) spiking in
      layer 2/3 (L2/3) pyramidal neurons in a cortical column of rat barrel cortex. The
      low AP rates in pyramidal neurons could be explained by activation of
      interneurons in L2/3 providing inhibition onto L2/3 pyramidal neurons. L2/3
      interneurons classified as local inhibitors based on their axonal projection in
      the same column were reported to receive strong excitatory input from spiny
      neurons in L4, which are also the main source of the excitatory input to L2/3
      pyramidal neurons. Here, we investigated the remaining synaptic connection in
      this intracolumnar microcircuit. We found strong and reliable inhibitory synaptic
      transmission between intracolumnar L2/3 local-inhibitor-to-L2/3 pyramidal neuron
      pairs [inhibitory postsynaptic potential (IPSP) amplitude -0.88 +/- 0.67 mV]. On
      average, 6.2 +/- 2 synaptic contacts were made by L2/3 local inhibitors onto L2/3
      pyramidal neurons at 107 +/- 64 um path distance from the pyramidal neuron soma,
      thus overlapping with the distribution of synaptic contacts from L4 spiny neurons
      onto L2/3 pyramidal neurons (67 +/- 34 um). Finally, using compartmental
      simulations, we determined the synaptic conductance per synaptic contact to be
      0.77 +/- 0.4 nS. We conclude that the synaptic circuit from L4 to L2/3 can
      provide efficient shunting inhibition that is temporally and spatially aligned
      with the excitatory input from L4 to L2/3. 

PMID- 25761639
TI  - Population Pharmacokinetics of ABT-806, an Investigational Anti-Epidermal Growth
      Factor Receptor (EGFR) Monoclonal Antibody, in Advanced Solid Tumor Types Likely
      to Either Over-Express Wild-Type EGFR or Express Variant III Mutant EGFR.
AB  - BACKGROUND AND OBJECTIVES: ABT-806 is a veneered 'humanized' recombinant
      IgG1kappa antibody that is specific for a unique epitope of human epidermal
      growth factor receptor (EGFR) expressed only on tumor cells with the EGFRde2-7
      (EGFRvIII) deletion mutant as well as tumors with wild-type amplified receptors.
      We aimed to develop a population pharmacokinetic model of ABT-806 in cancer
      patients, and to evaluate fixed versus body weight-based dosing regimens.
      METHODS: The pharmacokinetics of ABT-806 were evaluated in a phase I, open-label
      study in cancer patients following intravenous infusion of ABT-806 every other
      week. A total of 587 serum concentrations of ABT-806 from 61 patients were
      analyzed using non-linear mixed-effects modeling. The impact of body weight-based
      and fixed dosing of ABT-806 was evaluated using a simulation approach. RESULTS: A
      two-compartment model with linear elimination was used to describe the serum
      concentration-time data of ABT-806. The population estimates of the apparent
      clearance from the central (CLc) and peripheral (CLp) compartments were 0.011 and
      0.025 L/h, respectively. The apparent volume of distribution estimates of the
      central (V 1) and peripheral (V 2) compartments were 3.5 and 3.3 L, respectively.
      The estimates of inter-subject variability (percentage coefficient of variation)
      in CLc, CLp, V 1, and V 2 were 38, 37, 20, and 48 %, respectively. Albumin on CLc
      and body weight on V 1 were statistically significant covariates; however, they
      explained 18 and 30 % of the inter-individual variability of clearance and V 1,
      respectively. Simulation results indicated that fixed and body weight-based
      dosing regimens yield similar steady-state concentrations and overall
      variability. CONCLUSIONS: ABT-806 demonstrated a unique pharmacokinetic profile
      compared to the marketed monoclonal antibodies against EGFR. The analysis
      indicates it is feasible to switch to fixed doses in subsequent clinical trials
      of ABT-806.

PMID- 25761641
TI  - Sugarcane and mulberry silage supplementation of sheep during the peripartum
      period.
AB  - The aim of this study was to evaluate the effects of supplementation with silage
      made from sugarcane alone or mulberry and sugarcane on the gastrointestinal
      nematodes and hematological parameters in peripartum Santa Ines ewes. Three
      groups, each of 15 ewes, were supplemented with either 100 % sugarcane silage or
      sugarcane silage and mulberry at ratios of either 75:25 or 50:50. The variables
      analyzed were weight, body condition, packed cell volume, total plasma protein,
      hemoglobin, total leukocytes, eosinophils, and number of parasite eggs per gram
      of feces. All variables were measured individually every 14 days, making ten
      samples per ewe. Diets with sugarcane added to different proportions of mulberry
      branches did not influence the blood and parasitological parameters of Santa Ines
      sheep naturally infected in the peripartum period. 

PMID- 25761640
TI  - Non-canonical manifestations of familial Mediterranean fever: a changing
      paradigm.
AB  - Paroxysmal crises of fever and systemic inflammation herald familial
      Mediterranean fever (FMF), considered as the archetype of all inherited systemic
      autoinflammatory diseases. Inflammatory bouts are characterized by short-term and
      self-limited abdominal, thoracic, and/or articular symptoms which subside
      spontaneously. Erysipelas-like findings, orchitis, and different patterns of
      myalgia may appear in a minority of patients. In recent years, many non-classical
      manifestations have been reported in the clinical context of FMF, such as
      vasculitides and thrombotic manifestations, neurologic and sensory organ
      abnormalities, gastrointestinal diseases, and even macrophage activation
      syndrome. As FMF left unrecognized and untreated is ominously complicated by the
      occurrence of AA-amyloidosis, it is highly desirable that diagnosis of this
      autoinflammatory disorder with its multiple clinical faces can be contemplated at
      whatever age and brought forward.

PMID- 25761642
TI  - Status of colorectal cancer devices: present scenario.
AB  - PURPOSE: The purpose of this study was the colonoscopic detection and removal of
      neoplasia from the colorectum to prevent the development of colorectal cancer.
      METHOD: Various online medical databases were searched such as PubMed, ACS, NCI,
      NIH, WHO, etc. for relevant publications and clinical trials for new developments
      in colonoscopic devices that are intended for diagnostic visualization and
      therapeutic interventions of the digestive tract. RESULT: HD colon and I-Scan
      both has shown to increase the detection of sporadic adenomas with high quality.
      Third Eye Retroscope confers the backward view of colon, but aeroscope screens
      the entire colon in 30-60 min. Narrow-band imaging enhances mucosal and vascular
      details through the color differentiation of precancerous or cancerous polyp,
      compared to white light colonoscopy. The PillCam Colon Capsule is another new
      technique which is easily inserted and painless. In case of chemotherapy,
      Therasphere with Yttrium-90 has good results in the treatment of colorectal
      adenocarcinoma metastasis. Radiofrequency ablation is a good technique for tumors
      ablation and Staple Line Reinforcement prevents the leak during and post-surgery
      of colon. FOBT is much more sensitive and cheaper test for colorectal cancer
      screening. CONCLUSION: Registered clinical trials have shown promising results
      for neoplasia detection by I-Scan, TER, and NBI imaging techniques will change
      current colonoscopic practice in colorectal cancer screening. However, more
      studies and inventions are required for improving the patient safety and
      efficacy.

PMID- 25761643
TI  - Determination of urinary 5-hydroxyindoleacetic acid as a metabolomics in gastric
      cancer.
AB  - PURPOSE: The aim of this paper is to study urinary5-hydroxyindoleacetic acid (5
      HIAA) in gastric cancer patients with a biochemical method and compare this
      metabolite with normal control and individuals with chronic gastritis. MATERIALS
      AND METHODS: The subjects were 48 histologically proven gastric adenocarcinoma
      patients. They were 10 women and 38 men with mean age of 63.73 years. For
      determination of urinary excretion of 5-HIAA, a biochemical method was applied.
      According to kit protocol, the patients' fresh urine was added to the reagent
      material, and the color of the sediment that was the result of interaction
      between 5-HIAA and the mercury salt was compared with the standard colorimetric
      plate of the kit. The same method was also performed for a group of 47 patients
      with chronic gastritis and also a group of 50 normal individuals (age and sex
      matched). RESULTS: Urinary 5-HIAA was significantly higher in gastric cancer
      patients compared to individuals with chronic gastritis and normal controls (P
      value <0.001), but no association was detected in urinary 5-HIAA based on age,
      sex, or site of tumor and tumor grade in gastric cancer patients group. Also, no
      significant difference was noted in 5-HIAA excretion between chronic gastritis
      and normal control groups. CONCLUSION: Urinary excretion of 5-HIAA is
      significantly higher in the gastric cancer patients in comparison with that of
      chronic gastritis patients or normal individuals. So, this test could be regarded
      as a tumor marker in conjunction with other modalities in diagnosis of gastric
      cancer.

PMID- 25761644
TI  - Feasibility of using an iPod touch device and acceptability of a stigma reduction
      intervention with HIV-infected women in the Deep South.
AB  - As with many infectious diseases throughout history, stigma is a part of the
      trajectory of the HIV disease process. HIV-related stigma impedes women from
      being tested for HIV. Once infected, HIV-related stigma hinders women from
      disclosing their HIV status to sexual partners and health care providers,
      engaging in medical care, effectively self-managing the disease after infection,
      and adhering to anti-retroviral therapy. After three decades of the HIV epidemic,
      no evidenced-based, culturally relevant, gender-specific interventions exist to
      help women infected with HIV manage the stigma associated with HIV infection.
      This manuscript reports the feasibility of using an iPod touch device and
      acceptability of a stigma reduction intervention with HIV-infected women in the
      Deep South in a mixed-method, randomized clinical trial. Results from the study
      demonstrate that it is feasible to utilize an iPod touch device to deliver an HIV
      related stigma intervention to women. Further, women report that the HIV-related
      stigma intervention is acceptable and meaningful. 

PMID- 25761646
TI  - Fast 3D isotropic imaging of the aortic vessel wall by application of 2D
      spatially selective excitation and a new way of inversion recovery for black
      blood imaging.
AB  - PURPOSE: Aortic vessel wall imaging requires large coverage and a high spatial
      resolution, which makes it prohibitively time-consuming for clinical use. This
      work explores the feasibility of imaging the descending aorta in acceptable scan
      time, using two-dimensional (2D) spatially selective excitation and a new way of
      inversion recovery for black blood imaging. METHODS: The excitation pattern and
      field of view in a 3D gradient echo sequence are reduced in two dimensions,
      following the aorta's anisotropic geometry. Black blood contrast is obtained by
      partially inverting the blood's magnetization in the heart at the start of the
      cardiac cycle. Imaging is delayed until the inverted blood has filled the desired
      part of the aorta. The flip angle and delay are determined such that the blood
      signal is nulled upon arrival in the aorta. RESULTS: Experiments on eight
      volunteers showed that the descending aortic vessel wall could be imaged over
      more than 15 cm at a maximal resolution of 1.5 * 1.5 * 1.5 mm(3) in less than 5
      min minimal scan time. CONCLUSION: This feasibility study demonstrates that time
      efficient isotropic imaging of the descending aorta is possible by using 2D
      spatially selective excitation for motion artifact reduction and a new way of
      inversion recovery for black blood imaging.

PMID- 25761647
TI  - Iron regulation of hepcidin through Hfe and Hjv: Common or distinct pathways?

PMID- 25761645
TI  - A decade of pollen transcriptomics.
AB  - KEY MESSAGE: Overview of pollen transcriptome studies. Pollen development is
      driven by gene expression, and knowledge of the molecular events underlying this
      process has undergone a quantum leap in the last decade through studies of the
      transcriptome. Here, we outline historical evidence for male haploid gene
      expression and review the wealth of pollen transcriptome data now available.
      Knowledge of the transcriptional capacity of pollen has progressed from genetic
      studies to the direct analysis of RNA and from gene-by-gene studies to analyses
      on a genomic scale. Microarray and/or RNA-seq data can now be accessed for all
      phases and cell types of developing pollen encompassing 10 different angiosperms.
      These growing resources have accelerated research and will undoubtedly inspire
      new directions and the application of system-based research into the mechanisms
      that govern the development, function and evolution of angiosperm pollen.

PMID- 25761649
TI  - Energy Dependence of the Ruthenium(II)-Bipyridine Metal-to-Ligand-Charge-Transfer
      Excited State Radiative Lifetimes: Effects of pipi*(bipyridine) Mixing.
AB  - The variations in band shape with excited state energy found for the triplet
      metal to ligand charge transfer ((3)MLCT) emission spectra of ruthenium
      bipyridine (Ru-bpy) chromophores at 77 K have been postulated to arise from
      excited state/excited state configurational mixing. This issue is more critically
      examined through the determination of the excited state energy dependence of the
      radiative rate constants (kRAD) for these emissions. Experimental values for kRAD
      were determined relative to known literature references for Ru-bpy complexes.
      When the lowest energy excited states are metal centered, kRAD can be anomalously
      small and such complexes have been identified using density functional theory
      (DFT) modeling. When such complexes are removed from the energy correlation,
      there is a strong (3)MLCT energy-dependent contribution to kRAD in addition to
      the expected classical energy cubed factor for complexes with excited state
      energies greater than 10 000 cm(-1). This correlates with the DFT calculations
      which show significant excited state electronic delocalization between a pi(bpy
      orbital) and a half-filled dpi*-(Ru(III)-orbital) for Ru-bpy complexes with
      (3)MLCT excited state energies greater than about 16 000 cm(-1). Overall, this
      work implicates the "stealing" of emission bandshapes as well as intensity from
      the higher energy, strongly allowed bpy-centered singlet pipi* excited state. 

PMID- 25761648
TI  - Stable and efficient Paclitaxel nanoparticles for targeted glioblastoma therapy.
AB  - Development of efficient nanoparticles (NPs) for cancer therapy remains a
      challenge. NPs are required to have high stability, uniform size, sufficient drug
      loading, targeting capability, and ability to overcome drug resistance. In this
      study, the development of a NP formulation that can meet all these challenging
      requirements for targeted glioblastoma multiform (GBM) therapy is reported. This
      multifunctional NP is composed of a polyethylene glycol-coated magnetic iron
      oxide NP conjugated with cyclodextrin and chlorotoxin (CTX) and loaded with
      fluorescein and paclitaxel (PTX) (IONP-PTX-CTX-FL). The physicochemical
      properties of the IONP-PTX-CTX-FL are characterized by transmission electron
      microscope, dynamic light scattering, and high-performance liquid chromatography.
      The cellular uptake of NPs is studied using flow cytometry and confocal
      microscopy. Cell viability and apoptosis are assessed with the Alamar Blue
      viability assay and flow cytometry, respectively. The IONP-PTX-CTX-FL had a
      uniform size of ~44 nm and high stability in cell culture medium. Importantly,
      the presence of CTX on NPs enhanced the uptake of the NPs by GBM cells and
      improved the efficacy of PTX in killing both GBM and GBM drug-resistant cells.
      The IONP-PTX-CTX-FL demonstrated its great potential for brain cancer therapy and
      may also be used to deliver PTX to treat other cancers. 

PMID- 25761650
TI  - The impact of donor age and sex on the nucleated cell count and CD34 count in
      healthy bone marrow donors.
AB  - BM remains an important source of stem cells. The BM characteristics change with
      age but the estimation of CD34 calculation of one CD34+ cell per 100 nucleated
      cells is used for all donors including pediatric donors in the operating room
      before getting the actual CD34 count. In order to see whether this formula is
      applicable for pediatric donors, we designed a retrospective study to see the
      affect of the age and sex on the BM NCC, CD34 count, and CD34/NCC ratios. Ninety
      eight BM collections from 91 related donors were evaluated retrospectively
      (median age: nine yr [1.5-54 yr]; M/F: 41/50). A significant negative correlation
      was found between the donor age and NCC (r = -0.229, p < 0.05), CD34 count (r = 
      0.563, p < 0.01), and CD34/NCC (r = -0.664, p < 0.01). The negative correlation
      for CD34 count and CD34/NCC persisted in female and male donor groups. When
      donors younger than 16 yr of age were compared with the older donor group, the
      median NCC, median CD34 count, and CD34/NCC were significantly lower in the older
      group (p < 0.01). Age and sex have to be taken into consideration to avoid
      unnecessary high-volume collections and increased operating room time in the
      younger donors.

PMID- 25761651
TI  - Response to: The Literature Supports Policies Promoting Neonatal Male
      Circumcision in N. America.

PMID- 25761652
TI  - 28-Day hindlimb unweighting reduces expression of Rho kinase and inhibits its
      effects in femoral artery of rat.
AB  - Previous studies have demonstrated inconsistent roles of Rho kinase (ROCK) in the
      decreased vasoconstriction of rat hindquarter vessels induced by hindlimb
      unweighting (HU). The present study was designed to determine the unclear role of
      ROCK in the mediation of HU-induced decreased femoral arterial vasoconstriction.
      28-day HU rat was adopted as the animal model. With or without Y-27632, a ROCK
      inhibitor, isometric force of femoral artery was measured. The expression of ROCK
      and its effects on downstream targets were also examined. Results showed that (1)
      HU caused a significant decrease of the phenylephrine (PE)-evoked and potassium
      chloride (KCl)-evoked femoral arterial vasoconstriction (P < 0.05), confirming
      the functional findings by previous studies. (2) Inhibition of ROCK with Y-27632
      produced an equal reduction of the vasoconstriction in CON and HU. (3) HU
      significantly decreased ROCK II expression and the effects of ROCK on myosin
      light-chain phosphatase (MLCP) and MLC (P < 0.05), but increased p65 nuclear
      translocation (P < 0.05) and inducible nitric oxide synthase (iNOS) expression (P
      < 0.05). (4) HU significantly (P < 0.05) increased NO production in femoral
      arteries, with Y-27632 significantly (P < 0.01) amplifying this effect. These
      findings have revealed that 28-day HU reduced the expression and effects of ROCK
      on downstream targets both directly (MLCP and MLC) and possibly indirectly (NF
      kappaB/iNOS/NO pathway) related to vasoconstriction in femoral arteries. 

PMID- 25761653
TI  - Clopidogrel reduces apoptosis and promotes proliferation of human vascular
      endothelial cells induced by palmitic acid via suppression of the long non-coding
      RNA HIF1A-AS1 in vitro.
AB  - Cardiovascular disease (CVD) is recognized as a major and increasing health
      problem affected older subjects in China, and clopidogrel has been widely used
      for treatment of CVD patients such as atherosclerosis, myocardial infarction, and
      myocardial ischaemia-reperfusion damage. However, the molecular mechanisms of
      clopidogrel for treatment of CVD are only partially understood. This study
      investigated the effects of clopidogrel on palmitic acid-induced damage of human
      vascular endothelial cells (HUVECs), and the molecular mechanisms of LncRNA HIF1A
      AS1 in regulating the proliferation and apoptosis of HUVECs in vitro. We firstly
      established a damage model of HUVECs through palmitic acid (PA) treatment. And
      the effect of clopidogrel reducing PA-induced apoptosis of HUVECs was observed by
      the flow cytometric measurement. To further understand the molecular mechanism of
      clopidogrel rescues PA-induced apoptosis, we used human LncRNA PCR array to
      compare the LncRNA expression profile difference between clopidogrel-treated
      cells and control cells. The expression of LncRNA HIF 1 alpha-antisense RNA 1
      (HIF1A-AS1) was significantly altered in clopidogrel-treated cells. We further
      proved that suppression of HIF1A-AS1 by siRNA reduce PA-induced apoptosis and
      promote proliferation of HUVECs. Furthermore, we also demonstrated inhibition
      apoptosis effect by HIF1A-AS1 is related to mitochondrial apoptosis pathway.
      Hence, our results suggest that clopidogrel rescues apoptosis and promotes
      proliferation of PA-induced damage model of HUVECs through inhibiting the
      mediator LncRNA HIF1A-AS1. These findings indicate that LncRNA HIF1A-AS1 may play
      an important role in the pathogenesis of CVD, and provide a novel molecular
      mechanism of clopidogrel for treatment of CVD.

PMID- 25761655
TI  - Induction of protection in murine experimental models against Trichinella
      spiralis: an up-to-date review.
AB  - The parasitic nematode Trichinella spiralis, an aetiological agent of the disease
      known as trichinellosis, infects wild and domestic animals through contaminated
      pig meat, which is the major source for Trichinella transmission. Prevention of
      this disease by interrupting parasite transmission includes vaccine development
      for livestock; however, major challenges to this strategy are the complexity of
      the T. spiralis life cycle, diversity of stage-specific antigens, immune-evasion
      strategies and the modulatory effect of host responses. Different approaches have
      been taken to induce protective immune responses by T. spiralis immunogens. These
      include the use of whole extracts or excretory-secretory antigens, as well as
      recombinant proteins or synthesized epitopes, using murine experimental models
      for trichinellosis. Here these schemes are reviewed and discussed, and new
      proposals envisioned to block the zoonotic transmission of this parasite. 

PMID- 25761654
TI  - Learning-related brain hemispheric dominance in sleeping songbirds.
AB  - There are striking behavioural and neural parallels between the acquisition of
      speech in humans and song learning in songbirds. In humans, language-related
      brain activation is mostly lateralised to the left hemisphere. During language
      acquisition in humans, brain hemispheric lateralisation develops as language
      proficiency increases. Sleep is important for the formation of long-term memory,
      in humans as well as in other animals, including songbirds. Here, we measured
      neuronal activation (as the expression pattern of the immediate early gene ZENK)
      during sleep in juvenile zebra finch males that were still learning their songs
      from a tutor. We found that during sleep, there was learning-dependent
      lateralisation of spontaneous neuronal activation in the caudomedial nidopallium
      (NCM), a secondary auditory brain region that is involved in tutor song memory,
      while there was right hemisphere dominance of neuronal activation in HVC (used as
      a proper name), a premotor nucleus that is involved in song production and
      sensorimotor learning. Specifically, in the NCM, birds that imitated their tutors
      well were left dominant, while poor imitators were right dominant, similar to
      language-proficiency related lateralisation in humans. Given the avian-human
      parallels, lateralised neural activation during sleep may also be important for
      speech and language acquisition in human infants. 

PMID- 25761656
TI  - Achilles tendinitis in systemic lupus erythematosus: search for an associated
      inflammatory disease.
AB  - OBJECTIVES: Except for traumatic and iatrogenic causes, Achilles tendinitis (AT)
      is mostly encountered in the context of inflammatory rheumatic diseases. This
      study aimed to describe AT in systemic lupus erythematosus (SLE). PATIENTS AND
      METHODS: Among 158 SLE patients who fulfilled the SLE criteria of the ACR
      classification followed between 1980 and 2013, we selected those who experienced
      at least one episode of AT not caused by traumatic or toxicity factors. RESULTS:
      Eight patients (one male, seven females), median age 52 years (range: 35-68),
      presented with 11 episodes of AT within an average of 10.5 (0-21) years after SLE
      diagnosis. Clinical presentation of SLE was mainly cutaneous (eight of eight),
      and articular (seven of eight). Axial symptoms were reported in six patients, two
      of whom had HLA-B27-positive status, and fulfilled the Amor and European
      Spondylarthropathy Study Group criteria. Resolution of AT was good with
      nonsteroidal anti-inflammatory topical or systemic drug therapies, which kept SLE
      quiescent and avoided any increase of specific treatment. CONCLUSION: Although
      the association is rare, when AT occurs in SLE patients, physicians should look
      for associated spondylarthritis.

PMID- 25761657
TI  - Multibacillary leprosy mimicking systemic lupus erythematosus: case report and
      literature review.
AB  - Leprosy is an infectious chronic disease with a wide range of clinical and
      serological manifestations. We report a case of a woman presenting with a malar
      rash, painless oral ulcers, photosensitivity, arthritis, positive antinuclear
      antibodies test and leuko-lymphopenia. Our case illustrates an unusual
      presentation of leprosy initially diagnosed as systemic lupus erythematosus
      (SLE). After the confirmation of multibacillary leprosy and multidrug therapy
      recommended by the World Health Organization, a good clinical response was
      observed. Recognition of rheumatic manifestations in leprosy is important as they
      may be confused with SLE. A literature review is presented to encourage
      clinicians to consider leprosy as a differential diagnosis. Specifically in
      patients with unusual rheumatic manifestations and persistent skin lesions, and
      when neurological symptoms are present. Leprosy has not been eradicated, so
      misdiagnosis can be frequent. It is necessary to increase medical practitioner
      awareness in order start proper treatment. 

PMID- 25761658
TI  - Metabolic fingerprint after acute and under sustained consumption of a functional
      beverage based on grape skin extract in healthy human subjects.
AB  - Grape-derived polyphenols are considered to be one of the most promising
      ingredients for functional foods due to their health-promoting activities. We
      applied a HPLC-MS-based untargeted metabolomic approach in order to evaluate the
      impact of a functional food based on grape skin polyphenols on the urinary
      metabolome of healthy subjects. Thirty-one volunteers participated in two dietary
      crossover randomized intervention studies: with a single-dose intake (187 mL) and
      with a 15-day sustained consumption (twice per day, 187 mL per day in total) of a
      functional beverage (FB). Postprandial (4-hour) and 24-hour urine samples
      collected after acute consumption and on the last day of sustained FB
      consumption, respectively, were analysed using an untargeted HPLC-qTOF-MS
      approach. Multivariate modelling with subsequent application of an S-plot
      revealed differential mass features related to acute and prolonged consumption of
      FB. More than half of the mass features were shared between the two types of
      samples, among which several phase II metabolites of grape-derived polyphenols
      were identified at confidence level II. Prolonged consumption of FB was
      specifically reflected in urine metabolome by the presence of first-stage
      microbial metabolites of flavanols: hydroxyvaleric acid and hydroxyvalerolactone
      derivatives. Overall, several epicatechin and phenolic acid metabolites both of
      tissular and microbiota origin were the most representative markers of FB
      consumption. To our knowledge, this is one of the first studies where an
      untargeted LC-MS metabolomic approach has been applied in nutrition research on a
      grape-derived FB. 

PMID- 25761659
TI  - Prehospital decision system supports appropriate transfer of older adults direct
      to a community-based hospital.

PMID- 25761660
TI  - A checklist-based tool for postoperative complications may improve and
      standardise patient care.

PMID- 25761661
TI  - Abused women report different levels of care and support from general psychiatric
      services.

PMID- 25761663
TI  - Abstracts of the 2nd International Conference on Behavioral Addictions, March 16
      18, 2015, Budapest, Hungary.

PMID- 25761662
TI  - Physical activity, alcohol consumption, BMI and smoking status before and after
      prostate cancer diagnosis in the ProtecT trial: opportunities for lifestyle
      modification.
AB  - Associations between certain lifestyle characteristics and prostate cancer risk
      have been reported, and continuation post-diagnosis can adversely affect
      prognosis. We explored whether men make spontaneous changes to their physical
      activity and alcohol intake, body mass index (BMI) and smoking status, following
      a diagnosis of localised prostate cancer. A detailed diet, health and lifestyle
      questionnaire was completed by 511 participants within the Prostate Testing for
      Cancer and Treatment (ProtecT) randomised controlled trial, both before and 9
      months after a diagnosis of prostate cancer. Of 177 men who were insufficiently
      active before their diagnosis (median 0 activity units/week; IQR 0-9), 40.7% had
      increased their activity by a median of 22 U week(-1) (IQR 15-35) 9 months later,
      and there was weak evidence that men were more active after diagnosis than before
      (p = 0.07). Men categorised as "working" occupational social class and who were
      insufficiently active before diagnosis were 2.03 (95%, CI = 1.03-3.99, p = 0.04)
      times more likely to have increased their physical activity levels compared to
      men classified as "managerial or professional." Similarly, men who were
      insufficiently active pre-diagnosis and with T-stage 2 compared with T-stage 1
      prostate cancer were 2.47 (95%, CI = 1.29-4.71, p = 0.006) times more likely to
      be sufficiently active post-diagnosis. Following diagnosis, there was an overall
      reduction in alcohol intake (p = 0.03) and the proportion of current smokers (p =
      0.09), but no overall change in BMI. We conclude that some men spontaneously
      change certain lifestyle behaviours on receiving a diagnosis of prostate cancer.
      For many men, however, additional support through lifestyle interventions is
      probably required to facilitate and maintain these changes. 

PMID- 25761665
TI  - Cross-cultural and comparative epidemiology of insomnia: the Diagnostic and
      statistical manual (DSM), International classification of diseases (ICD) and
      International classification of sleep disorders (ICSD).
AB  - OBJECTIVE: To compare the prevalence of insomnia according to symptoms,
      quantitative criteria, and Diagnostic and Statistical Manual of Mental Disorders,
      4th and 5th Edition (DSM-IV and DSM-5), International Classification of Diseases,
      10th Revision (ICD-10), and International Classification of Sleep Disorders, 2nd
      Edition (ICSD-2), and to compare the prevalence of insomnia disorder between Hong
      Kong and the United States by adopting a similar methodology used by the America
      Insomnia Survey (AIS). METHODS: Population-based epidemiological survey
      respondents (n = 2011) completed the Brief Insomnia Questionnaire (BIQ), a
      validated scale generating DSM-IV, DSM-5, ICD-10, and ICSD-2 insomnia disorder.
      RESULTS: The weighted prevalence of difficulty falling asleep, difficulty staying
      asleep, waking up too early, and non-restorative sleep that occurred >=3 days per
      week was 14.0%, 28.3%, 32.1%, and 39.9%, respectively. When quantitative criteria
      were included, the prevalence dropped the most from 39.9% to 8.4% for non
      restorative sleep, and the least from 14.0% to 12.9% for difficulty falling
      asleep. The weighted prevalence of DSM-IV, ICD-10, ICSD-2, and any of the three
      insomnia disorders was 22.1%, 4.7%, 15.1%, and 22.1%, respectively; for DSM-5
      insomnia disorder, it was 10.8%. CONCLUSION: Compared with 22.1%, 3.9%, and 14.7%
      for DSM-IV, ICD-10, and ICSD-2 in the AIS, cross-cultural difference in the
      prevalence of insomnia disorder is less than what is expected. The prevalence is
      reduced by half from DSM-IV to DSM-5. ICD-10 insomnia disorder has the lowest
      prevalence, perhaps because excessive concern and preoccupation, one of its
      diagnostic criteria, is not always present in people with insomnia.

PMID- 25761664
TI  - Immobilized surfactant-nanotube complexes support selectin-mediated capture of
      viable circulating tumor cells in the absence of capture antibodies.
AB  - The metastatic spread of tumor cells from the primary site to anatomically
      distant organs leads to a poor patient prognosis. Increasing evidence has linked
      adhesive interactions between circulating tumor cells (CTCs) and endothelial
      cells to metastatic dissemination. Microscale biomimetic flow devices hold
      promise as a diagnostic tool to isolate CTCs and develop metastatic therapies,
      utilizing E-selectin (ES) to trigger the initial rolling adhesion of tumor cells
      under flow. To trigger firm adhesion and capture under flow, such devices also
      typically require antibodies against biomarkers thought to be expressed on CTCs.
      This approach is challenged by the fact that CTCs are now known to exhibit
      heterogeneous expression of conventional biomarkers. Here, we describe surfactant
      nanotube complexes to enhance ES-mediated capture and isolation of tumor cells
      without the use of capture antibodies. While the majority of tumor cells
      exhibited weaker rolling adhesion on halloysite nanotubes (HNT) coated with ES,
      HNT functionalization with the sodium dodecanoate (NaL) surfactant induced a
      switch to firm cellular adhesion under flow. Conversely, surfactant-nanotube
      complexes significantly reduced the number of primary human leukocytes captured
      via ES-mediated adhesion under flow. The switch in tumor cell adhesion was
      exploited to capture and isolate tumor cells in the absence of EpCAM antibodies,
      commonly utilized as the gold standard for CTC isolation. Additionally, HNT-NaL
      complexes were shown to capture tumor cells with low to negligible EpCAM
      expression, that are not efficiently captured using conventional approaches.

PMID- 25761666
TI  - The relationship between heart-carotid pulse transit time and carotid intima
      media thickness in hypertensive patients.
AB  - The study aimed to investigate the relationship between heart-carotid pulse
      transit time and carotid intima-media thickness (CIMT) in hypertensive patients,
      and whether including the pre-ejection period (PEP) in heart-carotid pulse
      transit time would affect this correlation. A total of 62 hypertensive patients
      were included in this study. They were divided into the normal CIMT group (n=33,
      CIMT?0.8 mm) and the thickened CIMT group (n=29, CIMT>0.8 mm). The noninvasive
      ultrasound method was used to measure CIMT, electrocardiogram R-wave-based heart
      carotid pulse transit time (rcPTT) and PEP. Aortic valve-carotid artery pulse
      transit time (acPTT) was calculated by subtracting PEP from rcPTT. Simple linear
      analysis showed that CIMT was negatively associated with rcPTT and acPTT (r=
      0.57, P<0.0001; r=-0.41, P=0.016) in the normal CIMT group as well as in the
      thickened CIMT group (r=-0.50, P=0.0053; r=-0.59, P=0.001). These relationships
      were eliminated in the normal CIMT group after adjusting for age, gender, smoking
      behaviour, systolic blood pressure, diastolic blood pressure and cholesterol
      levels. However, rcPTT and acPTT still showed significant correlations with CIMT
      in the thickened CIMT group. In conclusion, rcPTT and acPTT were associated with
      CIMT, independent of well-known clinical confounders in thickened CIMT
      hypertensive patients. Therefore, rcPTT and acPTT might be useful markers for
      atherosclerosis evaluation. 

PMID- 25761667
TI  - Obstructive sleep apnea, hypertension and cardiovascular diseases.
AB  - Obstructive sleep apnea (OSA) is characterized by recurrent episodes of partial
      (hypopnea) or complete interruption (apnea) in breathing during sleep due to
      airway collapse in the pharyngeal region. OSA and its cardiovascular consequences
      have been widely explored in observational and prospective studies. Most evidence
      verifies the positive relationship between OSA and hypertension, coronary artery
      disease, atrial fibrillation, stroke and heart failure. However, more studies are
      needed to better assess the impact of OSA, and possible benefit of treatment with
      continuous positive airway pressure (CPAP) on dyslipidemia, type 2 diabetes,
      insulin resistance and cardiovascular mortality. The leading pathophysiological
      mechanisms involved in the changes triggered by OSA, include intermittent
      hypoxemia and re-oxygenation, arousals and changes in intrathoracic pressure.
      Hypertension is strongly related with activation of the sympathetic nervous
      system, stimulation of the renin-angiotensin-aldosterone system and impairment of
      endothelial function. The high prevalence of OSA in the general population,
      hypertensive patients and especially obese individuals and patients resistant to
      antihypertensive therapy, highlights the need for effective screening, diagnosis
      and treatment of OSA to decrease cardiovascular risk. 

PMID- 25761668
TI  - Ubiquitous distribution of salts and proteins in spider glue enhances spider silk
      adhesion.
AB  - Modern orb-weaving spiders use micron-sized glue droplets on their viscid silk to
      retain prey in webs. A combination of low molecular weight salts and proteins
      makes the glue viscoelastic and humidity responsive in a way not easily achieved
      by synthetic adhesives. Optically, the glue droplet shows a heterogeneous
      structure, but the spatial arrangement of its chemical components is poorly
      understood. Here, we use optical and confocal Raman microscopy to show that salts
      and proteins are present ubiquitously throughout the droplet. The distribution of
      adhesive proteins in the peripheral region explains the superior prey capture
      performance of orb webs as it enables the entire surface area of the glue droplet
      to act as a site for prey capture. The presence of salts throughout the droplet
      explains the recent Solid-State NMR results that show salts directly facilitate
      protein mobility. Understanding the function of individual glue components and
      the role of the droplet's macro-structure can help in designing better synthetic
      adhesives for humid environments. 

PMID- 25761669
TI  - Structure, function and inhibition of the phosphoethanolamine methyltransferases
      of the human malaria parasites Plasmodium vivax and Plasmodium knowlesi.
AB  - Phosphoethanolamine methyltransferases (PMTs) catalyze the three-step methylation
      of phosphoethanolamine to form phosphocholine, a critical step in the synthesis
      of phosphatidylcholine in a select number of eukaryotes including human malaria
      parasites, nematodes and plants. Genetic studies in the malaria parasite
      Plasmodium falciparum have shown that the methyltransferase PfPMT plays a
      critical function in parasite development and differentiation. The presence of
      PMT orthologs in other malaria parasites that infect humans and their absence in
      mammals make them ideal targets for the development of selective antimalarials
      with broad specificity against different Plasmodium species. Here we describe the
      X-ray structures and biochemical properties of PMT orthologs from Plasmodium
      vivax and Plasmodium knowlesi and show that both enzymes are inhibited by
      amodiaquine and NSC158011, two drugs with potent antimalarial activity. Metabolic
      studies in a yeast mutant that relies on PkPMT or PvPMT for survival demonstrated
      that these compounds inhibit phosphatidylcholine biosynthesis from ethanolamine.
      Our structural and functional data provide insights into the mechanism of
      catalysis and inhibition of PMT enzymes and set the stage for a better design of
      more specific and selective antimalarial drugs. 

PMID- 25761670
TI  - Mst2 Controls Bone Homeostasis by Regulating Osteoclast and Osteoblast
      Differentiation.
AB  - Mammalian sterile 20-like kinase 2 (Mst2) plays a central role in the Hippo
      pathway, controlling cell proliferation, differentiation, and apoptosis during
      development. However, the roles of Mst2 in osteoclast and osteoblast development
      are largely unknown. Here, we demonstrate that mice deficient in Mst2 exhibit
      osteoporotic phenotypes with increased numbers of osteoclasts and decreased
      numbers of osteoblasts as shown by micro-computed tomography (uCT) and
      histomorphometric analyses. Osteoclast precursors lacking Mst2 exhibit increased
      osteoclastogenesis and Nfatc1, Acp5, and Oscar expression in response to receptor
      activator of NF-kappaB ligand (RANKL) exposure. Conversely, Mst2 overexpression
      in osteoclast precursors leads to the inhibition of RANKL-induced osteoclast
      differentiation. Osteoblast precursors deficient in Mst2 exhibit attenuated
      osteoblast differentiation and function by downregulating the expression of
      Runx2, Alpl, Ibsp, and Bglap. Conversely, ectopic expression of Mst2 in
      osteoblast precursors increases osteoblastogenesis. Finally, we demonstrate that
      the NF-kappaB pathway is activated by Mst2 deficiency during osteoclast and
      osteoblast development. Our findings suggest that Mst2 is involved in bone
      homeostasis, functioning as a reciprocal regulator of osteoclast and osteoblast
      differentiation through the NF-kappaB pathway.

PMID- 25761671
TI  - Cryo-EM structure of fatty acid synthase (FAS) from Rhodosporidium toruloides
      provides insights into the evolutionary development of fungal FAS.
AB  - Fungal fatty acid synthases Type I (FAS I) are up to 2.7 MDa large molecular
      machines composed of large multifunctional polypeptides. Half of the amino acids
      in fungal FAS I are involved in structural elements that are responsible for
      scaffolding the elaborate barrel-shaped architecture and turning fungal FAS I
      into highly efficient de novo producers of fatty acids. Rhodosporidium toruloides
      is an oleaginous fungal species and renowned for its robust conversion of
      carbohydrates into lipids to over 70% of its dry cell weight. Here, we use cryo
      EM to determine a 7.8-A reconstruction of its FAS I that reveals unexpected
      features; its novel form of splitting the multifunctional polypeptide chain into
      the two subunits alpha and beta, and its duplicated ACP domains. We show that the
      specific distribution into alpha and beta occurs by splitting at one of many
      possible sites that can be accepted by fungal FAS I. While, therefore, the
      specific distribution in alpha and beta chains in R. toruloides FAS I is not
      correlated to increased protein activities, we also show that the duplication of
      ACP is an evolutionary late event and argue that duplication is beneficial for
      the lipid overproduction phenotype.

PMID- 25761672
TI  - Trichoblastoma, syringocystadenoma papilliferum, desmoplastic trichilemmoma and
      tumor of the follicular infundibulum with signet-ring cells, all arising in nevus
      sebaceus.
AB  - Herein, we describe a 63-year-old male with multiple tumors arising within a
      nevus sebaceus on the posterior scalp. On histopathologic examination, four
      distinct tumors were identified: trichoblastoma, syringocystadenoma papilliferum,
      desmoplastic trichilemmoma and tumor of the follicular infundibulum (TFI). Within
      the TFI component of the nevus sebaceus, there was intracytoplasmic accumulation
      of eosinophilic keratin, as shown on pancytokeratin-stained sections, imparting a
      signet-ring appearance to the cells. To our knowledge, this is the first report
      of signet-ring cells arising within a TFI occurring in a nevus sebaceus. We
      discuss this case as well as review the literature on multiple tumors arising
      within nevus sebaceus and signet-ring cell changes in primary cutaneous tumors. 

PMID- 25761673
TI  - IL-23-mediated mononuclear phagocyte crosstalk protects mice from Citrobacter
      rodentium-induced colon immunopathology.
AB  - Gut homeostasis and mucosal immune defense rely on the differential contributions
      of dendritic cells (DC) and macrophages. Here we show that colonic CX3CR1(+)
      mononuclear phagocytes are critical inducers of the innate response to
      Citrobacter rodentium infection. Specifically, the absence of IL-23 expression in
      macrophages or CD11b(+) DC results in the impairment of IL-22 production and in
      acute lethality. Highlighting immunopathology as a death cause, infected animals
      are rescued by the neutralization of IL-12 or IFNgamma. Moreover, mice are also
      protected when the CD103(+) CD11b(-) DC compartment is rendered deficient for IL
      12 production. We show that IL-12 production by colonic CD103(+) CD11b(-) DC is
      repressed by IL-23. Collectively, in addition to its role in inducing IL-22
      production, macrophage-derived or CD103(-) CD11b(+) DC-derived IL-23 is required
      to negatively control the otherwise deleterious production of IL-12 by CD103(+)
      CD11b(-) DC. Impairment of this critical mononuclear phagocyte crosstalk results
      in the generation of IFNgamma-producing former TH17 cells and fatal
      immunopathology. 

PMID- 25761674
TI  - Brassinosteroids play a critical role in the regulation of pesticide metabolism
      in crop plants.
AB  - Pesticide residues in agricultural produce pose a threat to human health
      worldwide. Although the detoxification mechanisms for xenobiotics have been
      extensively studied in mammalian cells, information about the regulation network
      in plants remains elusive. Here we show that brassinosteroids (BRs), a class of
      natural plant hormones, decreased residues of common organophosphorus,
      organochlorine and carbamate pesticides by 30-70% on tomato, rice, tea, broccoli,
      cucumber, strawberry, and other plants when treated externally. Genome-wide
      microarray analysis showed that fungicide chlorothalonil (CHT) and BR co
      upregulated 301 genes, including a set of detoxifying genes encoding cytochrome
      P450, oxidoreductase, hydrolase and transferase in tomato plants. The level of
      BRs was closely related to the respiratory burst oxidase 1 (RBOH1)-encoded NADPH
      oxides-dependent H2O2 production, glutathione biosynthesis and the redox
      homeostasis, and the activity of glutathione S-transferase (GST). Gene silencing
      treatments showed that BRs decreased pesticide residues in plants likely by
      promoting their metabolism through a signaling pathway involving BRs-induced H2O2
      production and cellular redox change. Our study provided a novel approach for
      minimizing pesticide residues in crops by exploiting plants' own detoxification
      mechanisms. 

PMID- 25761675
TI  - A Filifactor alocis-centered co-occurrence group associates with periodontitis
      across different oral habitats.
AB  - Periodontitis is a highly prevalent polymicrobial disease worldwide, yet the
      synergistic pattern of the multiple oral pathogens involved is still poorly
      characterized. Here, saliva, supragingival and subgingival plaque samples from
      periodontitis patients and periodontally healthy volunteers were collected and
      profiled with 16S rRNA gene pyrosequencing. Different oral habitats harbored
      significantly different microbiota, and segregation of microbiota composition
      between periodontitis and health was observed as well. Two-step redundancy
      analysis identified twenty-one OTUs, including Porphyromonas gingivalis,
      Tannerella forsythia and Filifactor alocis, as potential pathogens that were
      significantly associated with periodontitis and with two periodontitis diagnostic
      parameters (pocket depth and attachment loss) in both saliva and supragingival
      plaque habitats. Interestingly, pairwise correlation analysis among the 21 OTUs
      revealed that Filifactor alocis was positively correlated with seven other
      putative pathogens (R > 0.6, P < 0.05), forming a co-occurrence group that was
      remarkably enriched in all three habitats of periodontitis patients. This
      bacterial cluster showed a higher diagnostic value for periodontitis than did any
      individual potential pathogens, especially in saliva. Thus, our study identified
      a potential synergistic ecological pattern involving eight co-infecting pathogens
      across various oral habitats, providing a new framework for understanding the
      etiology of periodontitis and developing new diagnoses and therapies. 

PMID- 25761677
TI  - Expanding client-centred thinking to include social determinants: a practical
      scenario based on the occupation of breastfeeding.
AB  - BACKGROUND: Client-centred thinking in occupational therapy underemphasizes the
      influence of social determinants and societal-level factors on occupation across
      the life course. When client-centred thinking focuses solely on the local or
      immediate contexts of individuals, therapists may not fully recognize or
      understand how social determinants can create barriers to occupational
      participation and performance. AIM/OBJECTIVES: This article critically examines
      gaps in traditional thinking concerning client-centredness and demonstrates how
      the complex interplay between social determinants and societal-level factors may
      lead to occupational injustices. MATERIAL AND METHODS: A practical example from a
      recent study on breastfeeding and accompanying scenario is used to examine
      limitations in current client-centred reasoning. The Life Course Health
      Development framework, a theoretical framework examining contexts of health
      disparities, is applied to illustrate the opportunity to expand thinking about
      client-centredness. RESULTS: The Life Course Health Development framework may be
      a useful addition to client-centred thinking about social determinants of
      occupation. CONCLUSION AND SIGNIFICANCE: Expanding client-centred thinking to
      include awareness, understanding, and respect for social determinants of
      occupation may enhance therapist-client interactions and outcomes of the
      occupational therapy process, and address gaps in current thinking that may
      contribute to occupational injustices.

PMID- 25761676
TI  - Severe adverse effects of bromocriptine in lactation inhibition: a
      pharmacovigilance survey.
AB  - OBJECTIVE: To assess the nature and conditions of the occurrence of adverse drug
      reactions (ADRs) of bromocriptine, which is used to inhibit lactation. DESIGN:
      Observational study. SETTING: Cases from the French pharmacovigilance database
      and the marketing authorisation holders. SAMPLE: Serious ADRs reported between
      1994 and 2010 in association with bromocriptine used for lactation inhibition in
      France. METHODS: Each case was checked to confirm the bromocriptine indication,
      the seriousness of the ADR, the modalities of bromocriptine use, and to identify
      possible associated predisposing factors. MAIN OUTCOME MEASURES: Number and
      description of serious ADRs, with a particular focus on misuse and associated
      predisposing factors. RESULTS: Among 105 serious ADRs, including two fatal cases,
      the most frequent were cardiovascular (70.5%), neurological (14.3%), and
      psychiatric (8.6%) disorders. Cardiovascular disorders primarily consisted of
      ischaemic manifestations (n = 47): acute ischaemic stroke (n = 18, one death),
      myocardial infarction (n = 11, one death), and reversible postpartum cerebral
      angiopathy (n = 10). Misuse was identified in 52 cases (70.3%) of cardiovascular
      disorders, and mostly consisted of bromocriptine continuation despite the
      occurrence of first symptoms suggesting an ADR or the absence of a progressive
      titration of bromocriptine. About half of these women had cardiovascular
      predisposing factors, mainly tobacco smoking, overweight or obesity, or a history
      of hypertension or pre-eclampsia. CONCLUSIONS: This survey, together with
      published data, provides further evidence that serious ADRs still occur after
      bromocriptine use in lactation inhibition, and that most of these ADRs could have
      been avoided. The use of bromocriptine should therefore be limited to cases where
      no other options are available to inhibit lactation.

PMID- 25761678
TI  - Multilevel quantile function modeling with application to birth outcomes.
AB  - Infants born preterm or small for gestational age have elevated rates of
      morbidity and mortality. Using birth certificate records in Texas from 2002 to
      2004 and Environmental Protection Agency air pollution estimates, we relate the
      quantile functions of birth weight and gestational age to ozone exposure and
      multiple predictors, including parental age, race, and education level. We
      introduce a semi-parametric Bayesian quantile approach that models the full
      quantile function rather than just a few quantile levels. Our multilevel quantile
      function model establishes relationships between birth weight and the predictors
      separately for each week of gestational age and between gestational age and the
      predictors separately across Texas Public Health Regions. We permit these
      relationships to vary nonlinearly across gestational age, spatial domain and
      quantile level and we unite them in a hierarchical model via a basis expansion on
      the regression coefficients that preserves interpretability. Very low birth
      weight is a primary concern, so we leverage extreme value theory to supplement
      our model in the tail of the distribution. Gestational ages are recorded in
      completed weeks of gestation (integer-valued), so we present methodology for
      modeling quantile functions of discrete response data. In a simulation study we
      show that pooling information across gestational age and quantile level
      substantially reduces MSE of predictor effects. We find that ozone is negatively
      associated with the lower tail of gestational age in south Texas and across the
      distribution of birth weight for high gestational ages. Our methods are available
      in the R package BSquare. 

PMID- 25761679
TI  - Online social networking and US poison control centers: Facebook as a means of
      information distribution.
AB  - BACKGROUND: Online social networking services such as Facebook provide a novel
      medium for the dissemination of public health information by poison control
      centers in the United States. We performed a cross-sectional study of poison
      control center Facebook pages to describe and assess the use of this medium.
      METHODS: Facebook pages associated with poison control centers were identified
      during a continuous two-week period from December 24, 2012 to January 7, 2013.
      Data were extracted from each page, including affiliated poison control center;
      page duration, measured in years since registration; number of subscribers;
      number of postings by general toxicological category; and measures of user
      generated activity including "likes", "shares", and comments per posting.
      RESULTS: Among the 56 US poison control centers, 39 Facebook pages were
      identified, of which 29 were currently active. The total number of active pages
      has increased by 140% from 2009 to 2013 (average of 25% per year). The total
      number of all subscribers to active pages was 11,211, ranging from 40 to 2,456
      (mean 387, SD 523), equal to 0.006% of all Facebook users in the United States.
      The number of subscribers per page was associated with page duration, number of
      postings, and type of postings. The types of toxicological postings were public
      education (45%), self-promotion (28%), childhood safety (12%), drugs of abuse
      (8%), environmental poisonings (6%), and general overdoses (1%). CONCLUSION:
      Slightly over half of all poison control centers in the United States are
      supplementing their outreach and education efforts through Facebook. In general,
      the more active the poison control center on Facebook, the more page followers
      and follower engagement gained.

PMID- 25761680
TI  - Oligonucleotide inhibitors of telomerase: prospects for anticancer therapy and
      diagnostics.
AB  - The activity of telomerase allows eukaryotic cells to have unlimited division
      potential. On its functioning, telomerase synthesizes short DNA repeats at the 3'
      end of DNA within chromosomes that ensures genome stability during cell division.
      Telomerase is active in the majority of cancer cell types and is virtually absent
      in somatic cells with rare exceptions. This difference allows us to consider
      inhibition of telomerase activity as a possible approach to antitumor therapy.
      Telomerase is a nucleoprotein composed of two main components: the reverse
      transcriptase (hTERT), which is a catalytic subunit, and telomerase RNA (hTR),
      which encodes a template for synthesis of repeats. The biogenesis and features of
      telomerase seem very promising for its inhibition due to complementary
      interactions. In this review, we analyze putative pathways of oligonucleotide
      influence on telomerase and consider the known native and modified
      oligonucleotide inhibitors of telomerase, as well as possible mechanisms of their
      action. We also discuss the application of telomerase-targeted oligonucleotide
      conjugates for in vivo imaging of tumor cells. 

PMID- 25761681
TI  - Rat liver sinusoidal surface N-linked glycoproteomic analysis by affinity
      enrichment and mass spectrometric identification.
AB  - Glycosylation in liver is one of the most biologically important protein
      modifications. It plays critical roles in many physiological and pathological
      processes by virtue of its unique location at the blood-tissue interface,
      including angiogenesis, liver cancer, cirrhosis, and fibrosis. To analyze
      glycosylation of plasma membrane proteins in liver sinusoidal endothelial cells
      (LSEC), N-glycopeptides of the LSEC surface were enriched using a filter-assisted
      sample preparation-based lectin affinity capture method and subsequently
      identified with mass spectrometry. In total, 225 unique N-glycosylation sites on
      152 glycoproteins were identified, of which 119 (53%) sites had not previously
      been determined experimentally. Among the glycoproteins, 53% were classified as
      plasma membrane proteins and 47 (31%) as signaling proteins and receptors.
      Moreover, 23 cluster of differentiation antigens with 49 glycopeptides were
      detected within the membrane glycoproteins of the liver sinusoidal surface.
      Furthermore, bioinformatics analysis revealed that the majority of identified
      glycoproteins have an impact on processes of LSEC. Therefore, N-glycoproteomic
      analysis of the liver sinusoidal surface may provide useful information on liver
      regeneration and facilitate liver disease diagnosis. 

PMID- 25761682
TI  - Downregulation of miR-221, -30d, and -15a contributes to pathogenesis of prostate
      cancer by targeting Bmi-1.
AB  - Prostate cancer is the second leading cause of cancer-related deaths of men. Bmi
      1, a member of PcG family of proteins, has been implicated in the pathogenesis of
      prostate cancer, and disturbed profile of microRNAs (miRNAs) has been found in
      prostate cancer tissues. How Bmi-1 is regulated by miRNAs is unclear. In this
      study, we screened 18 miRNAs that potentially repress the expression of Bmi-1
      using a dual luciferase system and found that 12 miRNAs could bind with the 3'
      untranslated region of Bmi-1 mRNA. Using qRT-PCR, we found that expression of miR
      221, -15a, and -30d was significantly reduced in prostate cancer tissues.
      Subsequent functional study indicated that miR-221 and miR-30d can repress
      prostate cancer cell proliferation, and this effect can be partially rescued by
      Bmi-1 overexpression. Our study constructs the relation between downregulated miR
      221 and miR-30d and prostate cancer pathogenesis. These results indicate that miR
      221 and miR-30d are candidate tumor suppressor miRNAs in prostate cancer and
      therefore serve as potential clinical classification markers and therapeutic
      targets for human prostate cancer. 

PMID- 25761683
TI  - Stratification of chondroitin sulfate binding sites in 3D-model of bovine
      testicular hyaluronidase and effective size of glycosaminoglycan coat of the
      modified protein.
AB  - A 3D-model of bovine testicular hyaluronidase (BTH) was constructed based on
      established tertiary structure of human hyaluronidase Hyal1 using a molecular
      homological modeling method in silico. The analysis of the BTH 3D-model
      demonstrated lysine residue stratification during enzyme modification. The 3D
      model of chondroitin sulfate (CHS)-modified hyaluronidase (BTH-CHS) was obtained
      by modeling covalent binding of lysine residues with benzoquinone-activated CHS.
      The degree of enzyme modification and the length of CHS chains were varied during
      3D modeling. The importance of deep BTH modification degree for the formation of
      active and stable enzyme derivatives was shown, as determined earlier
      experimentally. The effective size of the CHS coat for productive BTH
      modification was confirmed. It is theoretically achieved at the increase in
      molecular mass of BTH-CHS derivative to approximately 140-180 kDa and can be
      practically obtained, according to experimental data, using CHS of different
      molecular mass (30-50 as well as 120-140 kDa). 

PMID- 25761684
TI  - FoF1-ATP synthase of Streptomyces fradiae ATCC 19609: structural, biochemical,
      and functional characterization.
AB  - The patterns of protein phosphorylation in inverted membrane vesicles from the
      strain Streptomyces fradiae ATCC 19609 were investigated to elucidate the
      mechanisms of regulation of bacterial membrane bound FoF1-ATP synthase. We found
      for the first time by two-dimensional gel electrophoresis and mass spectrometry
      that the beta- and b-subunits of the FoF1-ATP synthase complex undergo
      phosphorylation; 20 proteins with known functions were identified. All eight
      subunits of FoF1-ATP synthase, i.e. alpha, beta, gamma, delta, epsilon, a, b, and
      c, were cloned into Escherichia coli and expressed as recombinant proteins. Using
      a crude preparation of serine/threonine protein kinases, we demonstrated the
      phosphorylation of recombinant gamma-, beta-, alpha- and epsilon-subunits. The
      beta-subunit was phosphorylated both as a recombinant protein and in vesicles.
      Differential phosphorylation of membrane-bound and recombinant proteins can be
      attributed to different pools of protein kinases in each preparation; in
      addition, certain steps of FoF1-ATP synthase assembly and function might be
      accompanied by individual phosphorylation patterns. The structure of the operon
      containing all subunits and regulatory protein I was identified. The phylogenetic
      similarity of FoF1-ATP synthase from Streptomyces fradiae ATCC 19609 with the
      respective proteins in saprophytic and pathogenic (including Mycobacterium
      tuberculosis) bacteria was investigated. Thus, bacterial serine/threonine protein
      kinases are important for the regulation of FoF1-ATP synthase. From the practical
      standpoint, our results provide a basis for designing targeted antibacterial
      drugs. 

PMID- 25761685
TI  - Epigenetic mechanisms of peptidergic regulation of gene expression during aging
      of human cells.
AB  - Expression levels of genes encoding specific transcription factors and other
      functionally important proteins vary upon aging of pancreatic and bronchial
      epithelium cell cultures. The peptides KEDW and AEDL tissue-specifically affect
      gene expression in pancreatic and bronchial cell cultures, respectively. It is
      established in this work that the DNA methylation patterns of the PDX1, PAX6,
      NGN3, NKX2-1, and SCGB1A1 gene promoter regions change upon aging in pancreatic
      and bronchial cell cultures in correlation with variations in their expression
      levels. Thus, stable changes in gene expression upon aging of cell cultures could
      be caused by changes in their promoter methylation patterns. The methylation
      patterns of the PAX4 gene in pancreatic cells as well as those of the FOXA1,
      SCGB3A2, and SFTPA1 genes in bronchial cells do not change upon aging and are
      unaffected by peptides, whereas their expression levels change in both cases. The
      promoter region of the FOXA2 gene in pancreatic cells contains a small number of
      methylated CpG sites, their methylation levels being affected by cell culture
      aging and KEDW, though without any correlation with gene expression levels. The
      promoter region of the FOXA2 gene is completely unmethylated in bronchial cells
      irrespective of cell culture age and AEDL action. Changes in promoter methylation
      might be the cause of age- and peptide-induced variations in expression levels of
      the PDX1, PAX6, and NGN3 genes in pancreatic cells and NKX2-1 and SCGB1A1 genes
      in bronchial cells. Expression levels of the PAX4 and FOXA2 genes in pancreatic
      cells and FOXA1, FOXA2, SCGB3A2, and SFTPA1 genes in bronchial cells seem to be
      controlled by some other mechanisms. 

PMID- 25761686
TI  - Hybrid structures of polycationic aluminum phthalocyanines and quantum dots.
AB  - Semiconductor nanocrystals (CdSe/ZnS quantum dots, QDs) were used as inorganic
      focusing antenna, allowing for the enhancement of fluorescence and
      photosensitizing activity of polycationic aluminum phthalocyanines (PCs). It was
      found that QDs form stable complexes with PCs in aqueous solutions due to
      electrostatic interactions. In such hybrid complexes, we observed highly
      efficient nonradiative energy transfer from QD to PC, leading to a sharp increase
      in the effective absorption cross section of PC in the absorption bands of the
      CdSe/ZnS quantum dots. When hybrid complexes are excited within these bands, the
      intensity of PC fluorescence and the rate of photosensitized singlet oxygen
      generation increases significantly (up to 500 and 350%, correspondingly) compared
      to free PC at the same concentration. The observed effect is of interest for
      modeling primary stages of photosynthesis and increasing photosensitizing
      activity of dyes used in photodynamic therapy. 

PMID- 25761687
TI  - Isolation, purification, and characterization of a stable defensin-like
      antifungal peptide from Trigonella foenum-graecum (fenugreek) seeds.
AB  - A novel defensin-like antifungal peptide (Tf-AFP) with molecular mass of 10.3 kDa
      was isolated from seeds of Trigonella foenum-graecum (fenugreek) by ammonium
      sulfate precipitation, cation-exchange, gel-filtration, hydrophobic
      chromatography, and RP-HPLC. Mass spectroscopic analysis revealed the intact mass
      of the purified antifungal peptide as 10321.5 Da and high similarity to plant
      defensins and other antifungal proteins in database search. 2D-PAGE showed pI
      value to be 8.8 and absence of isoforms. Isolated Tf-AFP inhibited growth of
      fungal species such as Fusarium oxysporum, Fusarium solani, and Rhizoctonia
      solani. The antifungal activity was inhibited in the presence of 50 mM NaCl.
      Circular dichroism analysis demonstrated that the protein is rich in beta-sheet
      structure and highly stable over a wide range of temperatures. Surprisingly,
      reduction of disulfide bridges and chemical denaturation did not produce large
      changes in secondary structure as judged by circular dichroism as well as by
      fluorescence spectroscopy. 

PMID- 25761688
TI  - Seasonal changes in isoform composition of giant proteins of thick and thin
      filaments and titin (connectin) phosphorylation level in striated muscles of
      bears (Ursidae, Mammalia).
AB  - Seasonal changes in the isoform composition of thick and thin filament proteins
      (titin, myosin heavy chains (MyHCs), nebulin), as well as in the phosphorylation
      level of titin in striated muscles of brown bear (Ursus arctos) and hibernating
      Himalayan black bear (Ursus thibetanus ussuricus) were studied. We found that the
      changes that lead to skeletal muscle atrophy in bears during hibernation are not
      accompanied by a decrease in the content of nebulin and intact titin-1 (T1)
      isoforms. However, a decrease (2.1-3.4-fold) in the content of T2 fragments of
      titin was observed in bear skeletal muscles (m. gastrocnemius, m. longissimus
      dorsi, m. biceps) during hibernation. The content of the stiffer N2B titin
      isoform was observed to increase relative to the content of its more compliant
      N2BA isoform in the left ventricles of hibernating bears. At the same time, in
      spite of the absence of decrease in the total content of T1 in the myocardium of
      hibernating brown bear, the content of T2 fragments decreased ~1.6-fold. The
      level of titin phosphorylation only slightly increased in the cardiac muscle of
      hibernating brown bear. In the skeletal muscles of brown bear, the level of titin
      phosphorylation did not vary between seasons. However, changes in the composition
      of MyHCs aimed at increasing the content of slow (I) and decreasing the content
      of fast (IIa) isoforms of this protein during hibernation of brown bear were
      detected. Content of MyHCs I and IIa in the skeletal muscles of hibernating
      Himalayan black bear corresponded to that in the skeletal muscles of hibernating
      brown bear. 

PMID- 25761689
TI  - Extraction of histone H1 and decondensation of nuclear chromatin with various Mg
      dependent organization levels under treatment with polyglutamic acid and
      distamycin.
AB  - Chromatin in rat liver nuclei under conditions of low ionic strength (20-25 mM)
      and [Mg2+] from 2 to 5 mM has a condensed structure (100-200 nm globules) and
      gives the same CD signal (320-340 nm) at interaction with the antibiotic
      distamycin A (DM). Reducing [Mg2+] to 1 mM leads to chromatin decondensation to
      30 nm structures and increases the CD signal. Poly-L-glutamic acid (PG) at weight
      ratio PG/DNA = 6 and in the presence of 5 mM Mg2+ extracts only about 1/8 of
      nuclear histone H1, preserving a condensed chromatin structure. Removal of about
      1/4 of H1 at 3 mM Mg2+ leads to chromatin decondensation to 30 nm fibrils.
      Extraction of about half of histone H1 at [Mg2+] <= 2 mM results in chromatin
      refolding to nucleosome fibrils. PG-decondensation leads to a significant
      increase in the CD signal. The main H1 extraction occurs in 1-2 min, but at all
      Mg2+ concentrations the more slowly PG extracted fraction is found comprising 5
      7% of nuclear H1. About 25% of leaving nuclear H1 can be extracted by PG in the
      presence of saturating DM concentration (molar DM/DNA = 0.1). H1 release depends
      significantly on the PG concentration. However, even at high weight ratio PG/DNA
      = 30 and DM/DNA = 0.1, about 5-10% of histone H1 remained in the nuclei.
      Decondensation of chromatin in the nucleus is not always proportional to the
      yield of extracted histone H1 and is weakened in the presence of positively
      charged DM or high concentrations of PG. Our results show that the interaction of
      DM with chromatin depends primarily on chromatin packaging, while PG extraction
      depends on [Mg2+] supporting this packaging. 

PMID- 25761690
TI  - Taurine modulates catalytic activity of cytochrome P450 3A4.
AB  - The influence of the biologically active compound taurine on the stability and
      catalytic properties of the hemoprotein cytochrome P450 3A4 has been
      investigated. The catalytic properties were analyzed by electrochemical methods
      (cyclic and square-wave voltammetry) using cytochrome P450 3A4 immobilized on the
      electrode. Taurine at concentrations in the range 10-70 uM stimulated the
      electrochemical reduction of cytochrome P450 3A4, and the reduction was the
      highest (115 +/- 3%) in the presence of 50 uM taurine. Taurine pronouncedly
      attenuated the itraconazol-caused inhibition of the P450 isoenzyme P450 3A4.
      Taurine protected cytochrome P450 3A4 due to stabilizing it during electrolysis
      at controlled voltage in the presence of erythromycin as a substrate. This
      protection was manifested by an increase in the amount of the "residual" reduced
      form of the hemoprotein (52 +/- 5 and 71 +/- 8%, respectively). 

PMID- 25761691
TI  - Normal level of sepsis-associated phenylcarboxylic acids in human serum.
AB  - Previous studies showed that large amounts of phenylcarboxylic acids (PhCAs) are
      accumulated in a septic patient's blood due to increased endogenous and microbial
      phenylalanine and tyrosine biotransformation. Frequently, biochemical aromatic
      amino acid transformation into PhCAs is considered functionally insignificant for
      people without monogenetic hereditary diseases. The blood of healthy people
      contains the same PhCAs that are typical for septic patients as shown in this
      paper. The overall serum PhCAs level was 6 uM on average as measured by gas
      chromatography with flame ionization detection. This level is a stable
      biochemical parameter indicating the normal metabolism of aromatic amino acids.
      The concentrations of PhCAs in the metabolic profile of healthy people are
      distributed as follows: phenylacetic ~ p-hydroxyphenyllactic > p
      hydroxyphenylacetic > phenyllactic ~ phenylpropionic > benzoic. We conclude that
      maintaining of stable PhCAs level in the serum is provided as the result of
      integration of human endogenous metabolic pathways and microbiota. 

PMID- 25761692
TI  - Heparan sulfate 6-O-sulfotransferase 3 is involved in bone marrow mesenchymal
      stromal cell osteogenic differentiation?.
AB  - The roles of sugar chains such as heparan sulfate (HS) in stem cell self-renewal
      and differentiation are poorly understood. HS is a sugar chain with linear
      sulfated polyanionic disaccharide repeating structures that interact with many
      proteins, including structural proteins in the extracellular matrix and growth
      factors and their receptors. Thus, unraveling the role of HS in stem cell self
      renewal and differentiation could provide new insights and technical routes in
      clinical stem cell applications. Here, we purified rat bone marrow mesenchymal
      stromal cells (BMMSCs) by density gradient centrifugation, analyzed mesenchymal
      stromal cell surface stemness marker expression by flow cytometry, and identified
      the sulfotransferases responsible for sulfation ester modification of HS. An
      osteogenic differentiation model was established by chemical induction reagents
      and confirmed via alkaline phosphatase (ALP) activity detection and the
      expression of the osteogenic differentiation markers Runx2 and Ocn. The
      expression profiles of HS sulfotransferases in rat BMMSCs before and after
      osteogenic induction were detected by RT-PCR and Western blot. Cell spheroids
      were formed in both control and osteogenic culture systems when BMMSCs were grown
      to high confluence. We determined that this type of cell spheroid was a highly
      calcified nodule by histochemical staining. Among all the sulfotransferases
      examined, heparan sulfate 6-O-sulfotransferase 3 (HS6ST3) mRNA and protein were
      upregulated in these calcified cell spheroids. HS6ST3 knockdown BMMSCs were
      established with RNA interference, and they had significantly lower ALP activity
      and decreased expression of the osteogenic differentiation markers Runx2 and Ocn.
      These findings suggest that HS6ST3 is involved in BMMSC differentiation, and new
      glycotherapeutic-based technologies could be developed in the future. 

PMID- 25761693
TI  - Solving the Sustainable Growth Rate formula conundrum continues steps toward cost
      savings and care improvements.
AB  - Congress is again attempting to repeal the Sustainable Growth Rate (SGR) formula.
      The formula is a failed mechanism intended to constrain Medicare Part B physician
      spending by adjusting annual physician fee updates. Congress has averted formula
      driven physician fee cuts each year beginning in 2003 by overriding the SGR,
      usually accompanied with last-minute disputes about how these overrides should be
      paid for. Last year Congress achieved bipartisan and bicameral agreement on
      legislation to replace the SGR-the SGR Repeal and Medicare Provider Payment
      Modernization Act of 2014, which we refer to as the "2014 SGR fix"-but was unable
      to find a way to pay for the legislation under current budget rules. Current
      congressional deliberations appear focused on how to pay for the fix, with wide
      consensus that the 2014 legislation should remain the basic model for reform. We
      describe key features of the 2014 SGR fix, place it in the context of both past
      and ongoing Medicare health policy, assess its strengths and weaknesses as a
      mechanism to foster improved care and lower costs in Medicare, and suggest
      further actions to ensure success in meeting these goals.

PMID- 25761694
TI  - Music therapists' research activity and utilization barriers: a survey of the
      membership.
AB  - BACKGROUND: Music therapists have access to a rapidly expanding body of research
      supporting the use of music-based interventions. What is not known is the extent
      to which music therapists access these resources and what factors may prevent
      them from incorporating research findings into clinical work. OBJECTIVE: After
      constructing the Music Therapists' Research Activity and Utilization Barrier
      (MTRAUB) database, the purposes of this study involved: assessing the extent to
      which American Music Therapy Association (AMTA) members engage in certain
      research-related activities; and identifying respondents' perceived barriers to
      integrating research into clinical practice. METHODS: This study employed a
      quantitative, non-experimental approach using an online survey. Respondents
      included professional, associate, student/graduate student, retired, inactive,
      and honorary life members of AMTA. Instrumentation involved a researcher-designed
      Background Questionnaire as well as the Barriers to Research Utilization Scale
      (BARRIERS; Funk, Champagne, Wiese, & Tornquist, 1991), a tool designed to assess
      perceived barriers to incorporating research into practice. RESULTS: Of the 3,194
      survey invitations distributed, 974 AMTA members replied (a response rate of
      30%). Regarding research-related activities, descriptive findings indicate that
      journal reading is the most frequently reported research-related activity while
      conducting research is the least frequently reported activity. Results from the
      BARRIERS Scale indicated that Organizational and Communication factors are
      perceived as interfering most prominently with the ability to utilize research in
      clinical practice. CONCLUSIONS: Findings suggest that research-related activity
      and perceived barriers vary as a function of educational attainment, work
      setting, and occupational role. The author discusses these differential findings
      in detail, suggests supportive mechanisms to encourage increased research
      activity and utilization, and offers recommendations for further analysis of the
      MTRAUB data.

PMID- 25761695
TI  - Immunohistochemical changes and atrophy after chronic ethanol intoxication in rat
      salivary glands.
AB  - Alcoholism in humans is a chronic and progressive disease, characterized by loss
      of ethanol consumption control. Previous studies have reported that prolonged
      exposure to ethanol was responsible for alterations in glandular tissues of human
      and rodents. However, the interrelationship between ethanol and the glandular
      system is still the subject of numerous investigations, including the possible
      resistance of the submandibular gland (SG). In the present study, we investigated
      whether chronic ethanol exposure during adolescence may affect the parotid gland
      (PG) and SG in female rats. Female rats (n=16) were treated with distilled water
      or ethanol (dose of 6.5 g/kg/day, 22.5% w/v) through gavage for 55 days. Glands
      were collected, weighed and submitted to histological processing. Morphometric
      analysis was assessed by parenchymal and stromal area measurements. Smooth muscle
      actin (alpha-SMA), cytokeratin-19 (CK19) and apoptotic caspase-3 (CAS) were
      measured using ImageJ(r) software. Chronic ethanol administration did not alter
      the body weight of rats after treatment, although it increased glandular weight
      (p<0.001), reduced the parenchyma area (p<0.001) and decreased CK19 and alpha-SMA
      immunostainning in the PG. Besides, ethanol induced CK19 and CAS overexpression,
      and the occurrence of duct-like structures in SG. These results suggest that
      ethanol induces histological and morphometric changes in salivary glands of
      female rats intoxicated with ethanol during adolescence. Furthermore, the
      mechanism underlying these alterations needs to be investigated but may be not
      related to the inflammatory process.

PMID- 25761696
TI  - Management of soft tissue defects of the foot.

PMID- 25761699
TI  - Blockade of the dorsomedial hypothalamus and the perifornical area inhibits
      respiratory responses to arousing and stressful stimuli.
AB  - The dorsomedial hypothalamus (DMH) and the perifornical area (DMH/PeF) is one of
      the key regions of central autonomic processing. Previous studies have
      established that this region contains neurons that may be involved in respiratory
      processing; however, this has never been tested in conscious animals. The aim of
      our study was to investigate the involvement of the DMH/PeF area in mediating
      respiratory responses to stressors of various intensities and duration. Adult
      male Wistar rats (n = 8) received microinjections of GABAA agonist muscimol or
      saline into the DMH/PeF bilaterally and were subjected to a respiratory recording
      using whole body plethysmography. Presentation of acoustic stimuli (500-ms white
      noise) evoked transient responses in respiratory rate, proportional to the
      stimulus intensity, ranging from +44 +/- 27 to +329 +/- 31 cycles/min (cpm).
      Blockade of the DMH/PeF almost completely abolished respiratory rate and tidal
      volume responses to the 40- to 70-dB stimuli and also significantly attenuated
      responses to the 80- to 90-dB stimuli. Also, it significantly attenuated
      respiratory rate during the acclimatization period (novel environment stress).
      The light stimulus (30-s 2,000 lux) as well as 15-min restraint stress
      significantly elevated respiratory rate from 95 +/- 4.0 to 236 +/- 29 cpm and
      from 117 +/- 5.2 to 189 +/- 13 cpm, respectively; this response was abolished
      after the DMH/PeF blockade. We conclude that integrity of the DMH/PeF area is
      essential for generation of respiratory responses to both stressful and alerting
      stimuli. 

PMID- 25761698
TI  - Resveratrol restored Nrf2 function, reduced renal inflammation, and mitigated
      hypertension in spontaneously hypertensive rats.
AB  - Compelling evidence supports the role of oxidative stress and renal interstitial
      inflammation in the pathogenesis of hypertension. Resveratrol is a polyphenolic
      stilbene, which can lower oxidative stress by activating the transcription factor
      nuclear factor-E2-related factor-2 (Nrf2), the master regulator of numerous genes
      encoding antioxidant and phase II-detoxifying enzymes and molecules. Given the
      role of oxidative stress and inflammation in the pathogenesis of hypertension, we
      conducted this study to test the hypothesis that long-term administration of
      resveratrol will attenuate renal inflammation and oxidative stress and, hence,
      progression of hypertension in the young spontaneously hypertensive rats (SHR).
      SHR and control [Wistar-Kyoto (WKY)] rats were treated for 9 wk with resveratrol
      or vehicle in their drinking water. Vehicle-treated SHR exhibited renal
      inflammatory injury and oxidative stress, as evidenced by glomerulosclerosis,
      tubulointerstitial injury, infiltration of inflammatory cells, and increased
      levels of renal 8-isoprostane and protein carbonylation. This was associated with
      reduced antioxidant capacity and downregulations of Nrf2 and phase II antioxidant
      enzyme glutathione-S-transferase (GST). Resveratrol treatment mitigated renal
      inflammation and injury, reduced oxidative stress, normalized antioxidant
      capacity, restored Nrf2 and GST activity, and attenuated the progression of
      hypertension in SHR. However, resveratrol had no effect on these parameters in
      WKY rats. In conclusion, development and progression of hypertension in the SHR
      are associated with inflammation, oxidative stress, and impaired Nrf2-GST
      activity in the kidney. Long-term administration of resveratrol restores Nrf2
      expression, ameliorates inflammation, and attenuates development of hypertension
      in SHR. Clinical studies are needed to explore efficacy of resveratrol in human
      hypertension. 

PMID- 25761700
TI  - Sodium distribution predicts the chill tolerance of Drosophila melanogaster
      raised in different thermal conditions.
AB  - Many insects, including the model holometabolous insect Drosophila melanogaster,
      display remarkable plasticity in chill tolerance in response to the thermal
      environment experienced during development or as adults. At low temperatures,
      many insects lose the ability to regulate Na(+) balance, which is suggested to
      cause a secondary loss of hemolymph water to the tissues and gut lumen that
      concentrates the K(+) remaining in the hemolymph. The resultant increase in
      extracellular [K(+)] inhibits neuromuscular excitability and is proposed to cause
      cellular apoptosis and injury. The present study investigates whether and how
      variation in chill tolerance induced through developmental and adult cold
      acclimation is associated with changes in Na(+), water, and K(+) balance.
      Developmental and adult cold acclimation improved the chilling tolerance of D.
      melanogaster in an additive manner. In agreement with the proposed model, these
      effects were intimately related to differences in Na(+) distribution prior to
      cold exposure, such that chill-tolerant flies had low hemolymph [Na(+)], while
      intracellular [Na(+)] was similar among treatment groups. The low hemolymph Na(+)
      of cold-acclimated flies allowed them to maintain hemolymph volume, prevent
      hyperkalemia, and avoid injury following chronic cold exposure. These findings
      extend earlier observations of hemolymph volume disruption during cold exposure
      to the most ubiquitous model insect (D. melanogaster), highlight shared
      mechanisms of developmental and adult thermal plasticity and provide strong
      support for ionoregulatory failure as a central mechanism of insect chill
      susceptibility.

PMID- 25761697
TI  - Chronic hyperleptinemia results in the development of hypertension in pregnant
      rats.
AB  - Despite the fact that obesity is a major risk factor for preeclampsia (PE), the
      pathophysiological mechanisms whereby obesity and metabolic factors such as
      leptin increase this risk are unclear. While human data have shown that
      hyperleptinemia is associated with PE, the long-term effect of hyperleptinemia on
      blood pressure during pregnancy is unknown. Thus we tested the hypothesis whether
      chronic circulating leptin elevations in pregnant rats increase blood pressure
      and placental factors known to play a role in PE. On gestational day (GD)14, rats
      were assigned to the normal pregnant group with food intake ad libitum (control),
      leptin-treated (0.5 MUg.kg(-1).min(-1) ip) pregnant group with food intake ad
      libitum (pregnant+LEP), and normal pregnant group with food intake adjusted to
      the food intake of pregnant+LEP rats (pregnant-FR). On GD19, mean arterial
      pressure (MAP) was assessed and tissues were collected. Serum leptin
      concentration was elevated in pregnant+LEP compared with control and pregnant-FR
      (18.0 +/- 2.8 vs. 0.8 +/- 0.1 vs. 0.3 +/- 0.1 ng/ml; P < 0.05), which was
      associated with increased MAP (121.3 +/- 8.1 vs. 102.4 +/- 2.4 vs. 101.3 +/- 1.8
      mmHg; P < 0.05). Food intake and body weight were reduced in pregnant+LEP and
      pregnant-FR by the end of gestation. Additionally, placentas and fetuses of these
      groups were lighter than those of control. However, placental expression of tumor
      necrosis factor-alpha was significantly greater in pregnant+LEP compared with
      controls (1.6 +/- 0.1 vs. 1.1 +/- 0.1 pg/mg; P < 0.05). In conclusion, leptin
      increases blood pressure and placental tumor necrosis factor-alpha during
      pregnancy despite its effect of reducing food intake and body weight, and
      represents a mechanism whereby obesity can promote the development of
      hypertension in PE.

PMID- 25761701
TI  - Long-term measurement of renal cortical and medullary tissue oxygenation and
      perfusion in unanesthetized sheep.
AB  - The role of renal cortical and medullary hypoxia in the development of acute
      kidney injury is controversial, partly due to a lack of techniques for the long
      term measurement of intrarenal oxygenation and perfusion in conscious animals. We
      have, therefore, developed a methodology to chronically implant combination
      probes to chronically measure renal cortical and medullary tissue perfusion and
      oxygen tension (tPO2) in conscious sheep and evaluated their responsiveness and
      reliability. A transit-time flow probe and a vascular occluder were surgically
      implanted on the left renal artery. At the same operation, dual fiber-optic
      probes, comprising a fluorescence optode to measure tPO2 and a laser-Doppler
      probe to assess tissue perfusion, were inserted into the renal cortex and
      medulla. In recovered conscious sheep (n = 8) breathing room air, mean 24-h
      cortical and medullary tPO2 were similar (31.4 +/- 0.6 and 29.7 +/- 0.7 mmHg,
      respectively). In the renal cortex and medulla, a 20% reduction in renal blood
      flow (RBF) decreased perfusion (14.6 +/- 8.6 and 41.2 +/- 8.5%, respectively) and
      oxygenation (48.1 +/- 8.5 and 72.4 +/- 8.5%, respectively), with greater
      decreases during a 50% reduction in RBF. At autopsy, minimal fibrosis was
      observed around the probes. In summary, we have developed a technique to
      chronically implant fiber-optic probes in the renal cortex and medulla for
      recording tissue perfusion and oxygenation over many days. In normal resting
      conscious sheep, cortical and medullary tPO2 were similar. The responses to and
      recovery from renal artery occlusion, together with the consistent measurements
      over a 24-h period, demonstrate the responsiveness and stability of the probes.

PMID- 25761702
TI  - Socioeconomic position and survival after lung cancer: Influence of stage,
      treatment and comorbidity among Danish patients with lung cancer diagnosed in
      2004-2010.
AB  - BACKGROUND: To address social inequality in survival after lung cancer, it is
      important to consider how socioeconomic position (SEP) influences prognosis. We
      investigated whether SEP influenced receipt of first-line treatment and whether
      socioeconomic differences in survival could be explained by differences in stage,
      treatment and comorbidity. MATERIAL AND METHODS: In the Danish Lung Cancer
      Register, we identified 13 045 patients with lung cancer diagnosed in 2004-2010,
      with information on stage, histology, performance status and first-line
      treatment. We obtained age, gender, vital status, comorbid conditions and
      socioeconomic information (education, income and cohabitation status) from
      nationwide population-based registers. Associations between SEP and receipt of
      first-line treatment were analysed in multivariate logistic regression models and
      those with overall mortality in Cox regression models with stepwise inclusion of
      possible mediators. RESULTS: For both low- and high-stage lung cancer, adjusted
      ORs for first-line treatment were reduced in patients with short education and
      low income, although the OR for education did not reach statistical significance
      in men with high-stage disease. Patients with high-stage disease who lived alone
      were less likely to receive first-line treatment. The socioeconomic difference in
      overall survival was partly explained by differences in stage, treatment and
      comorbidity, although some differences remained after adjustment. Among patients
      with high-stage disease, the hazard ratio (HR) for death of those with low income
      was 1.12 (95% CI 1.05-1.19) in comparison with those with high income. Among
      patients with low-stage disease, those who lived alone had a 14% higher risk for
      dying (95% CI 1.05-1.25) than those who lived with a partner. The differences in
      risk for death by SEP were greatest in the first six months after diagnosis.
      CONCLUSION: Socioeconomic differences in survival after lung cancer are partly
      explained by social inequality in stage, first-line treatment and comorbidity.
      Efforts should be made to improve early diagnosis and adherence to first-line
      treatment recommendations among disadvantaged lung cancer patients.

PMID- 25761703
TI  - In memoriam - Joachim Mark, MD, PhD (1935-2014).

PMID- 25761705
TI  - Application of Eshelby's Solution to Elastography for Diagnosis of Breast Cancer.
AB  - Eshelby's solution is the analytical method that can derive the elastic field
      within and around an ellipsoidal inclusion embedded in a matrix. Since breast
      tumor can be regarded as an elastic inclusion with different elastic properties
      from those of surrounding matrix when the deformation is small, we applied
      Eshelby's solution to predict the stress and strain fields in the breast
      containing a suspicious lesion. The results were used to investigate the
      effectiveness of strain ratio (SR) from elastography in representing modulus
      ratio (MR) that may be the meaningful indicator of the malignancy of the lesion.
      This study showed that SR significantly underestimates MR and is varied with the
      shape and the modulus of the lesion. Based on the results from Eshelby's solution
      and finite element analysis (FEA), we proposed a surface regression model as a
      polynomial function that can predict the MR of the lesion to the matrix. The
      model has been applied to gelatin-based phantoms and clinical ultrasound images
      of human breasts containing different types of lesions. The results suggest the
      potential of the proposed method to improve the diagnostic performance of breast
      cancer using elastography. 

PMID- 25761706
TI  - Highly bright multicolour emission through energy migration in core/shell
      nanotubes.
AB  - This paper describes a simple and environmentally-friendly approach that allowed
      for the facile synthesis of a gadolinium-based core/shell/shell nanotube
      structure with a set of lanthanide ions incorporated into separated layers. In
      addition, by the rational design of a core/shell structure we systematically
      investigated the luminescence properties of different lanthanide ions in NaGdF4
      host, and efficient down-conversion emission can be realized through gadolinium
      sublattice-mediated energy migration. The Gd(3+) ions play an intermediate role
      in this process. By changing the doped lanthanide ions, we generated multicolour
      emissions from the luminescent Ln(3+) centers via energy transfer of Ce(3+)
      >Gd(3+)->Ln(3+) and Ce(3+)->Ln(3+) (Ln = Eu, Tb, Dy and Sm) in separated layers.
      Due to the strong absorption of ultraviolet (UV) irradiation by Ce(3+) ions, the
      luminescence efficiency could be enhanced after doping Ce(3+) ions in the shell.
      In NaGdF4:5% Eu(3+)@NaGdF4@NaGdF4:5% Ce(3+) core/shell/shell nanotubes, with
      increasing the NaGdF4 interlayer thickness, a gradual decrease in emission
      intensity was observed for the Eu(3+) activator. 

PMID- 25761704
TI  - TRPM7 inhibitor carvacrol protects brain from neonatal hypoxic-ischemic injury.
AB  - BACKGROUND: Our previous study found that suppression of TRPM7 reduced neuronal
      death in adult rat ischemic brain injury. It was reported that carvacrol blocked
      TRPM7 and attenuated brain injury in an adult rat MCAO model. The effects of
      carvacrol on neonatal stroke remain unknown. This study investigated the effects
      of carvacrol on neuronal injury and behavioral impairment after hypoxia-ischemia
      in neonatal mice and the potential signaling pathway underlying these effects.
      RESULTS: Carvacrol inhibited TRPM7 current in HEK293 cells over-expressing TRPM7
      and TRPM7-like current in hippocampal neurons in a dose-dependent manner.
      Carvacrol (>200 MUM) reduced OGD-induced neuronal injury in cortical neurons. 24
      hours after HI, TRPM7 protein level in the ipsilateral hemisphere was
      significantly higher than in the contralateral hemisphere. Carvacrol (30 and 50
      mg/kg) pre-treatment reduced brain infarct volume 24 hours after HI in a dose
      dependent manner. Carvacrol pre-treatment also improved neurobehavioral outcomes.
      Furthermore, animals pre-treated with carvacrol had fewer TUNEL-positive cells in
      the brain compared to vehicle-treated animals 3 days after HI. Carvacrol pre
      treatment also increased Bcl-2/Bax and p-Akt/t-Akt protein ratios and decreased
      cleaved caspase-3 protein expression 24 hours after HI. CONCLUSIONS: Carvacrol
      pre-treatment protects against neonatal hypoxic-ischemic brain injury by reducing
      brain infarct volume, promoting pro-survival signaling and inhibiting pro
      apoptotic signaling, as well as improving behavioral outcomes. The
      neuroprotective effect may be mediated by the inhibition of TRPM7 channel
      function. Carvacrol is a potential drug development target for the treatment of
      neonatal stroke.

PMID- 25761707
TI  - Identification of nuclear low-copy genes and their phylogenetic utility in
      rosids.
AB  - By far, the interordinal relationships in rosids remain poorly resolved. Previous
      studies based on chloroplast, mitochondrial, and nuclear DNA has produced
      conflicting phylogenetic resolutions that has become a widely concerned problem
      in recent phylogenetic studies. Here, a total of 96 single-copy nuclear gene loci
      were identified from the KOG (eukaryotic orthologous groups) database, most of
      which were first used for phylogenetic analysis of angiosperms. The orthologous
      sequence datasets from completely sequenced genomes of rosids were assembled for
      the resolution of the position of the COM (Celastrales-Oxalidales-Malpighiales)
      clade in rosids. Our analysis revealed strong and consistent support for CM
      topology (the COM clade as sister to the malvids). Our results will contribute to
      further exploring the underlying cause of conflict between chloroplast,
      mitochondrial, and nuclear data. In addition, our study identified a few novel
      nuclear molecular markers with potential to investigate the deep phylogenetic
      relationship of plants or other eukaryotic taxonomical groups. 

PMID- 25761708
TI  - Utilization of the organ care system - a game-changer in combating donor organ
      shortage.
AB  - For patients with end-stage heart failure, cardiac transplantation persists to be
      the gold standard. Nevertheless, the availability of organs remains a main
      constraint to the treatment. Through mounting usage of ex vivo heart perfusion an
      increase in organ availability was achieved by reconditioning of organs formerly
      not regarded as appropriate for transplantation. We propose the future standard
      application of this state-of-the-art technology to improve the pool of donor
      organs by evaluating hearts outside standard acceptability criteria. 

PMID- 25761709
TI  - The impact of demographic changes on the epidemiology of herpes zoster: Spain as
      a case study.
AB  - Varicella zoster virus (VZV) causes varicella upon first exposure and may
      reactivate later in life into herpes zoster (HZ), with a risk that is thought to
      be reduced by re-exposures to VZV. Given the decades-long time scales of
      reactivation and its dependence on the accumulation of re-exposure episodes,
      adopting a long-term perspective may be useful to correctly interpret current
      epidemiological trends of VZV. In this study, we investigate the possible impact
      of demographic changes on varicella and HZ in Spain, using an age-structured
      mathematical model informed with historical demographic data and calibrated
      against age-specific profiles of varicella seroprevalence and HZ incidence data.
      The model qualitatively reproduces the remarkable growth of HZ incidence observed
      in Spain between 1997 and 2004, before the introduction of varicella vaccination
      programmes. We demonstrate that this growth may be partially ascribed to the
      reduction of varicella circulation that followed the overall decline of the birth
      rate in the twentieth century. Model predictions further suggest that, even under
      the most optimistic projections, HZ incidence will continue its rise until at
      least 2040. Considering the effect of demographic changes can help interpreting
      variations in epidemiological trends of HZ, contributing to a more accurate
      evaluation of vaccination programmes against VZV. 

PMID- 25761710
TI  - Expression of parasite genetic variation changes over the course of infection:
      implications of within-host dynamics for the evolution of virulence.
AB  - How infectious disease agents interact with their host changes during the course
      of infection and can alter the expression of disease-related traits. Yet by
      measuring parasite life-history traits at one or few moments during infection,
      studies have overlooked the impact of variable parasite growth trajectories on
      disease evolution. Here we show that infection-age-specific estimates of host and
      parasite fitness components can reveal new insight into the evolution of
      parasites. We do so by characterizing the within-host dynamics over an entire
      infection period for five genotypes of the castrating bacterial parasite
      Pasteuria ramosa infecting the crustacean Daphnia magna. Our results reveal that
      genetic variation for parasite-induced gigantism, host castration and parasite
      spore loads increases with the age of infection. Driving these patterns appears
      to be variation in how well the parasite maintains control of host reproduction
      late in the infection process. We discuss the evolutionary consequences of this
      finding with regard to natural selection acting on different ages of infection
      and the mechanism underlying the maintenance of castration efficiency. Our
      results highlight how elucidating within-host dynamics can shed light on the
      selective forces that shape infection strategies and the evolution of virulence. 

PMID- 25761711
TI  - Glacial refugia and modern genetic diversity of 22 western North American tree
      species.
AB  - North American tree species, subspecies and genetic varieties have primarily
      evolved in a landscape of extensive continental ice and restricted temperate
      climate environments. Here, we reconstruct the refugial history of western North
      American trees since the last glacial maximum using species distribution models,
      validated against 3571 palaeoecological records. We investigate how modern
      subspecies structure and genetic diversity corresponds to modelled glacial
      refugia, based on a meta-analysis of allelic richness and expected heterozygosity
      for 473 populations of 22 tree species. We find that species with strong genetic
      differentiation into subspecies had widespread and large glacial refugia, whereas
      species with restricted refugia show no differentiation among populations and
      little genetic diversity, despite being common over a wide range of environments
      today. In addition, a strong relationship between allelic richness and the size
      of modelled glacial refugia (r(2) = 0.55) suggest that population bottlenecks
      during glacial periods had a pronounced effect on the presence of rare alleles. 

PMID- 25761712
TI  - Evaluating the metapopulation consequences of ecological traps.
AB  - Ecological traps occur when environmental changes cause maladaptive habitat
      selection. Despite their relevance to metapopulations, ecological traps have been
      studied predominantly at local scales. How these local impacts scale up to affect
      the dynamics of spatially structured metapopulations in heterogeneous landscapes
      remains unexplored. We propose that assessing the metapopulation consequences of
      traps depends on a variety of factors that can be grouped into four categories:
      the probability of encounter, the likelihood of selection, the fitness costs of
      selection and species-specific vulnerability to these costs. We evaluate six
      hypotheses using a network-based metapopulation model to explore the relative
      importance of factors across these categories within a spatial context. Our model
      suggests (i) traps are most severe when they represent a large proportion of
      habitats, severely reduce fitness and are highly attractive, and (ii) species
      with high intrinsic fitness will be most susceptible. We provide the first
      evidence that (iii) traps may be beneficial for metapopulations in rare
      instances, and (iv) preferences for natal-like habitats can magnify the effects
      of traps. Our study provides important insight into the effects of traps at
      landscape scales, and highlights the need to explicitly consider spatial context
      to better understand and manage traps within metapopulations. 

PMID- 25761713
TI  - The direct cost of traumatic secretion transfer in hermaphroditic land snails:
      individuals stabbed with a love dart decrease lifetime fecundity.
AB  - Several taxa of simultaneously hermaphroditic land snails exhibit a conspicuous
      mating behaviour, the so-called shooting of love darts. During mating, such land
      snail species transfer a specific secretion by stabbing a mating partner's body
      with the love dart. It has been shown that sperm donors benefit from this
      traumatic secretion transfer, because the secretions manipulate the physiology of
      a sperm recipient and increase the donors' fertilization success. However, it is
      unclear whether reception of dart shooting is costly to the recipients.
      Therefore, the effect of sexual conflict and antagonistic arms races on the
      evolution of traumatic secretion transfer in land snails is still controversial.
      To examine this effect, we compared lifetime fecundity and longevity between the
      individuals that received and did not receive dart shooting from mating partners
      in Bradybaena pellucida. Our experiments showed that the dart-receiving snails
      suffered reduction in lifetime fecundity and longevity. These results suggest
      that the costly mating behaviour, dart shooting, generates conflict between sperm
      donors and recipients and that sexually antagonistic arms races have contributed
      to the diversification of the morphological and behavioural traits relevant to
      dart shooting. Our findings also support theories suggesting a violent escalation
      of sexual conflict in hermaphroditic animals.

PMID- 25761714
TI  - Orientation behaviour of leatherback sea turtles within the North Atlantic
      subtropical gyre.
AB  - Leatherback sea turtles (Dermochelys coriacea) travel thousands of kilometres
      between temperate feeding and tropical breeding/over-wintering grounds, with
      adult turtles able to pinpoint specific nesting beaches after multi-year
      absences. Their extensive migrations often occur in oceanic habitat where limited
      known sensory information is available to aid in orientation. Here, we examined
      the migratory orientation of adult male, adult female and subadult leatherbacks
      during their open-ocean movements within the North Atlantic subtropical gyre by
      analysing satellite-derived tracks from fifteen individuals over a 2-year period.
      To determine the turtles' true headings, we corrected the reconstructed tracks
      for current drift and found negligible differences between current-corrected and
      observed tracks within the gyre. Individual leatherback headings were remarkably
      consistent throughout the subtropical gyre, with turtles significantly oriented
      to the south-southeast. Adult leatherbacks of both sexes maintained similar mean
      headings and showed greater orientation precision overall. The consistent
      headings maintained by adult and subadult leatherbacks within the gyre suggest
      use of a common compass sense. 

PMID- 25761716
TI  - Mechanisms of programmed cell death signaling in hair cells and support cells
      post-electrode insertion trauma.
AB  - CONCLUSION: Programmed cell death (PCD) initially starts in the support cells
      (SCs) after electrode insertion trauma (EIT), followed by PCD in hair cells
      (HCs). Activation of caspase-3 was observed only in SCs. Protecting both SCs and
      HCs with selective otoprotective drugs at an early stage post implantation may
      help to preserve residual hearing. OBJECTIVES: Cochlear implant EIT can initiate
      sensory cell losses via necrosis and PCD within the organ of Corti, which can
      lead to a loss of residual hearing. PCD appears to be a major factor in HC loss
      post-EIT. The current study aimed to: (1) determine the onset of PCD in both SCs
      and HCs within the traumatized organ of Corti; and (2) identify the molecular
      mechanisms active within the HCs and SCs that are undergoing PCD. METHODS: Adult
      guinea pigs were assigned to one of two groups: (1) EIT and (2) unoperated
      contralateral ears as controls. Immunostaining of dissected organ of Corti
      surface preparations for phosphorylated-Jun, cleaved caspase-3, and 4-hydroxy-2,3
      nonenal (HNE) were performed at 6, 12, and 24 h post-EIT and for contralateral
      control ears. RESULTS: At 6 h post-EIT the SCs immunolabeled for the presence of
      phosphorylated-Jun and activated caspase-3. Phosphorylated p-Jun labeling was
      observed at 12 h in both the HCs and SCs of middle and basal cochlear turns.
      Cleaved caspase-3 was not observed in HCs of any cochlear turn at up to 24 h post
      EIT. Lipid peroxidation (HNE immunostaining) was first observed at 12 h post-EIT
      in both the HCs and SCs of the basal turn, and reached the apical turn by 24 h
      post-EIT.

PMID- 25761717
TI  - Establishing cancer risks associated with PMS2 germline mutations in Lynch
      syndrome.

PMID- 25761715
TI  - Multiomics in grape berry skin revealed specific induction of the stilbene
      synthetic pathway by ultraviolet-C irradiation.
AB  - Grape (Vitis vinifera) accumulates various polyphenolic compounds, which protect
      against environmental stresses, including ultraviolet-C (UV-C) light and
      pathogens. In this study, we looked at the transcriptome and metabolome in grape
      berry skin after UV-C irradiation, which demonstrated the effectiveness of omics
      approaches to clarify important traits of grape. We performed transcriptome
      analysis using a genome-wide microarray, which revealed 238 genes up-regulated
      more than 5-fold by UV-C light. Enrichment analysis of Gene Ontology terms showed
      that genes encoding stilbene synthase, a key enzyme for resveratrol synthesis,
      were enriched in the up-regulated genes. We performed metabolome analysis using
      liquid chromatography-quadrupole time-of-flight mass spectrometry, and 2,012
      metabolite peaks, including unidentified peaks, were detected. Principal
      component analysis using the peaks showed that only one metabolite peak,
      identified as resveratrol, was highly induced by UV-C light. We updated the
      metabolic pathway map of grape in the Kyoto Encyclopedia of Genes and Genomes
      (KEGG) database and in the KaPPA-View 4 KEGG system, then projected the
      transcriptome and metabolome data on a metabolic pathway map. The map showed
      specific induction of the resveratrol synthetic pathway by UV-C light. Our
      results showed that multiomics is a powerful tool to elucidate the accumulation
      mechanisms of secondary metabolites, and updated systems, such as KEGG and KaPPA
      View 4 KEGG for grape, can support such studies.

PMID- 25761718
TI  - Epidemiology of pneumococcal carriage in children under five years of age in
      Accra, Ghana.
AB  - BACKGROUND: Although the majority of pneumococcal infections occur in the
      developing world, pneumococcal epidemiology is poorly understood in these
      settings. The aim of the study was to investigate the epidemiology of
      pneumococcal carriage among children younger than 5 years at a paediatric
      healthcare centre in Ghana. METHOD: Four-hundred and twenty-three children were
      randomly sampled and nasopharyngeal specimens were collected from them. The
      specimens were cultured for Streptococcus pneumoniae, and the isolates were
      subjected to antibiotic susceptibility testing and serotyping by latex
      agglutination. Epidemiological data on demographic and clinical features of the
      study subjects were collected. RESULTS: The prevalence of pneumococcal carriage
      was 48.9% (207/422), with age groups 43-48 months having the highest carriage
      prevalence. In the multivariate analysis, pneumococcal carriage was significantly
      associated with runny nose (odds ratio = 1.9, p = 0.003) and day-care attendance
      (odds ratio = 1.5, p = 0.04). No pneumococcal resistance was observed for
      ceftriaxone, while the prevalence of resistance to the other antibiotics tested
      was: cotrimoxazole 100%, ampicillin 88%, tetracycline 78%, penicillin 63% and
      erythromycin 24%. Fourteen different pneumococcal serogroups/serotypes were
      identified and serogroup 6 was the most prevalent (30%), followed by serotype 19
      (20%). CONCLUSIONS: We conclude that pneumococcal carriage among the study
      children is high and the carried strains have a high level of resistance (> 50%)
      to several antibiotics. Ceftriaxone is a suitable antibiotic for treating
      pneumococcal infections in Ghana, and the use of this antibiotic coupled with the
      pneumococcal vaccination is expected to significantly reduce the burden of
      pneumococcal disease in the country.

PMID- 25761719
TI  - Reply to Lance: "Mean platelet volume needs standardisation. Comment on Asher et
      al. Thromb Haemost 2014; 112: 137-141".

PMID- 25761721
TI  - Integration of bacteriorhodopsin with upconversion nanoparticles for NIR
      triggered photoelectrical response.
AB  - Transient spikes from the bacteriorhodopsin (bR) photocycle are triggered with
      NIR irradiation for the first time by integrating bR with upconversion
      nanoparticles. This work may open new horizons for the bR applications in the IR
      wavelength range. 

PMID- 25761720
TI  - Neighborhood Social Environment and Patterns of Depressive Symptoms Among
      Patients with Type 2 Diabetes Mellitus.
AB  - This study sought to examine whether neighborhood social environment was related
      to patterns of depressive symptoms among primary care patients with type 2
      diabetes mellitus (DM). Neighborhood social environment was assessed in 179
      patients with type 2 DM. Individual patient residential data at baseline was geo
      coded at the tract level and was merged with measures of neighborhood social
      environment. Depressive symptoms at baseline and at 12-week follow up were
      assessed using the nine-item Patient Health Questionnaire (PHQ-9). Patients in
      neighborhoods with high social affluence, high residential stability, and high
      neighborhood advantage were much less likely to have a persistent pattern of
      depressive symptoms compared to a pattern of few or no depressive symptoms
      (adjusted odds ratio (OR) = 0.06, 95 % confidence interval (CI) [0.01, 0.36]).
      Detrimental neighborhood influences may amplify risk for persistent depressive
      symptoms.

PMID- 25761722
TI  - Transcriptome analysis reveals the potential mechanism of the albino skin
      development in pufferfish Takifugu obscurus.
AB  - Our aim was to explore the potential mechanism underlying albino in Takifugu
      obscurus. The transcriptome sequencing of the skin samples from normal T.
      obscurus and albino ones was conducted in this paper. The differentially
      expressed genes (DEGs) in albino fish compared with controls were assayed. The
      gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) pathway
      analysis were performed to explore the differentially expressed gene (DEG)
      related functions and pathways. A total of 32 genes were found to be
      differentially expressed, including eight upregulated ones and 24 downregulated
      ones. Five GO terms were significantly enriched such as hemoglobin complex and
      oxygen transporter activity. The significantly enriched pathways contained
      linoleic acid metabolism and arachidonic acid metabolism. Hemoglobin complex,
      linoleic, and arachidonic acid metabolism may dysregulated in albino fugu.
      Dietary control of the linoleic acid and arachidonic acid may be an effective
      management for mediating albino in T. obscurus. 

PMID- 25761723
TI  - A fetal human heart cardiac-inducing RNA (CIR) promotes the differentiation of
      stem cells into cardiomyocytes.
AB  - A specific human fetal heart RNA has been discovered, which has the ability to
      induce myocardial cell formation from mouse embryonic and human-induced
      pluripotent stem cells in culture. In this study, commercially obtained RNA from
      human fetal heart was cloned, sequenced, and synthesized using standard
      laboratory approaches. Molecular analyses of the specific fetal cardiac-inducing
      RNA (CIR), revealed that it is a fragment of N-sulfoglucosaminesulfohydrolase and
      the caspase recruitment domain family member 14 precursor. Stem cells transfected
      with CIRs often form into spindle-shaped cells characteristic of
      cardiomyocytes,and express the cardiac-specific contractile protein marker,
      troponin-T, in addition to tropomyosin and alpha-actinin as detected by
      immunohistochemical staining. Expression of these contractile proteins showed
      organization into sarcomeric myofibrils characteristic of striated cardiac muscle
      cells. Computer analyses of the RNA secondary structures of the active CIR show
      significant similarities to a RNA from salamander or myofibril-inducing RNA
      (MIR), which also promotes non-muscle cells to differentiate into cardiac muscle.
      Thus, these two RNAs, salamander MIR and the newly discovered human-cloned CIR
      reported here, appear to have evolutionarily conserved secondary structures
      suggesting that both play major roles in vertebrate heart development and,
      particularly, in the differentiation of cardiomyocytes from non-muscle cells
      during development. 

PMID- 25761724
TI  - Establishment and characterization of two new cell lines from the mosquito
      Armigeres subalbatus (Coquillett) (Diptera: Culicidae).
AB  - Armigeres subalbatus (Coquillett) is a medically important mosquito and a model
      species for immunology research. We successfully established two cell lines from
      the neonate larvae of A. subalbatus using two different media. To our knowledge,
      this is the first report of an established Armigeres mosquito cell line. The cell
      lines, designated as Ar-3 and Ar-13, consist of adherent and diploid cells with
      compact colonies. Both these cell lines grow slowly after passage at a split
      ratio of 1:5 and a population doubling time of 2.7 and 3.0 d, respectively.
      Random amplified polymorphic DNA polymerase chain reaction (RAPD-PCR) was used to
      confirm that these lines correspond to the species of origin and are clearly
      distinct from seven other insect cell lines. Furthermore, reverse-transcription
      PCR was used to demonstrate that the Ar-3 cell line is susceptible to the
      Japanese encephalitis virus and two insect flaviviruses associated with Culex and
      Aedes mosquitoes but relatively insensitive to dengue virus. These data indicate
      that the newly established cell lines are cellular models of A. subalbatus as
      well as beneficial tools for the propagation of viruses associated with the
      Armigeres mosquito.

PMID- 25761726
TI  - Cine MRI: a new approach to the diagnosis of scapholunate dissociation.
AB  - OBJECTIVE: To evaluate the feasibility of cine MRI for the detection of
      scapholunate dissociation (SLD) and to compare the sensitivity and specificity of
      cine MRI with those of cineradiography and arthroscopy. MATERIALS AND METHODS: To
      evaluate feasibility, healthy subjects underwent cine MRI of the wrist. To
      evaluate sensitivity and specificity, patients with clinically suspected
      scapholunate ligament (SLL) injury after trauma to the wrist were prospectively
      included and underwent radiographic examination, cineradiography, and cine MRI.
      In 25 out of 38 patients, subsequent arthroscopy was performed. Results of
      cineradiography and cine MRI correlated with those of arthroscopy. RESULTS: Cine
      MRI was of diagnostic quality in all healthy subjects and patients with good
      interrater agreement. There was excellent correlation between cineradiography and
      cine MRI. Scapholunate distance differed significantly between healthy subjects
      and patients with scapholunate dissociation (p < 0.001), but not between imaging
      modalities in the patient group. Cine MRI had 85% sensitivity and 90% specificity
      for the detection of SLD. CONCLUSION: Cine MRI of the wrist is a fast and
      reliable technique for the detection of SLD with diagnostic accuracy comparable
      to cineradiography. It can be easily implemented as a routine clinical MRI
      examination, facilitating diagnostic workup of patients with suspected SLD while
      avoiding radiation exposure.

PMID- 25761727
TI  - Direct comparison of conventional radiography and cone-beam CT in small bone and
      joint trauma.
AB  - OBJECTIVE: To compare the diagnostic value of cone-beam computed tomography
      (CBCT) and conventional radiography (CR) after acute small bone or joint trauma.
      MATERIALS AND METHODS: Between March 2013 and January 2014, 231 patients with
      recent small bone or joint trauma underwent CR and subsequent CBCT. CR and CBCT
      examinations were independently assessed by two readers, blinded to the result of
      the other modality. The total number of fractures as well as the number of
      complex fractures were compared, and inter- and intraobserver agreement for CBCT
      was calculated. In addition, radiation doses and evaluation times for both
      modalities were noted and statistically compared. RESULTS: Fracture detection on
      CBCT increased by 35% and 37% for reader 1 and reader 2, respectively, and
      identification of complex fractures increased by 236% and 185%. Interobserver
      agreement for CBCT was almost perfect, as was intraobserver agreement for reader
      1. The intraobserver agreement for reader 2 was substantial. Radiation doses and
      evaluation time were significantly higher for CBCT. CONCLUSION: CBCT detects
      significantly more small bone and joint fractures, in particular complex
      fractures, than CR. In the majority of cases, the clinical implication of the
      additionally detected fractures is limited, but in some patients (e.g., fracture
      dislocations), the management is significantly influenced by these findings. As
      the radiation dose for CBCT substantially exceeds that of CR, we suggest adhering
      to CR as the first-line examination after small bone and joint trauma and keeping
      CBCT for patients with clinical-radiographic discordance or suspected complex
      fractures in need of further (preoperative) assessment.

PMID- 25761728
TI  - Correlation between the dielectric properties and biological activities of human
      ex vivo hepatic tissue.
AB  - Dielectric properties are vital biophysical features of biological tissues, and
      biological activity is an index to ascertain the active state of tissues. This
      study investigated the potential correlation between the dielectric properties
      and biological activities of human hepatic tissue with prolonged ex vivo time
      through correlation and regression analyses. The dielectric properties of 26
      cases of normal human hepatic tissue at 10 Hz to 100 MHz were measured from 15
      min after isolation to 24 h at 37  degrees C with 90% humidity. Cell
      morphologies, including nucleus area (NA) and alteration rate of intercellular
      area (ICAR), were analyzed as indicators of biological activities. Conductivity,
      complex resistivity, and NA exhibited opposing changes 1 h after isolation.
      Relative permittivity and ex vivo time were not closely correlated (p > 0.05).
      The dielectric properties measured at low frequencies (i.e. <1 MHz) were more
      sensitive than those measured at high frequencies in reflecting the biological
      activity of ex vivo tissue. Highly significant correlations were found between
      conductivity, resistivity and the ex vivo time (p < 0.05) as well as conductivity
      and the cell morphology (p < 0.05). The findings indicated that establishing the
      correlation between the dielectric properties and biological activities of human
      hepatic tissue is of great significance for promoting the role of dielectric
      properties in biological science, particularly in human biology.

PMID- 25761729
TI  - Projection of osteoporosis-related fractures and costs in China: 2010-2050.
AB  - A state-transition microsimulation model was used to project the substantial
      economic burden to the Chinese healthcare system of osteoporosis-related
      fractures. Annual number and costs of osteoporosis-related fractures were
      estimated to double by 2035 and will increase to 5.99 (95 % CI 5.44, 6.55)
      million fractures costing $25.43 (95 % CI 23.92, 26.95) billion by 2050.
      Consequently, cost-effective intervention policies must urgently be identified in
      an attempt to minimize the impact of fractures. INTRODUCTION: The aim of the
      study was to project the osteoporosis-related fractures and costs for the Chinese
      population aged >=50 years from 2010 to 2050. METHODS: A state-transition
      microsimulation model was used to simulate the annual incident fractures and
      costs. The simulation was performed with a 1-year cycle length and from the
      Chinese healthcare system perspective. Incident fractures and annual costs were
      estimated from 100 unique patient populations for year 2010, by multiplying the
      age- and sex-specific annual fracture risks and costs of fracture by the
      corresponding population totals in each of the 100 categories. Projections for
      2011-2050 were performed by multiplying the 2010 risks and costs of fracture by
      the respective annual population estimates. Costs were presented in 2013 US
      dollars. RESULTS: Approximately 2.33 (95 % CI 2.08, 2.58) million osteoporotic
      fractures were estimated to occur in 2010, costing $9.45 (95 % CI 8.78, 10.11)
      billion. Females sustained approximately three times more fractures than males,
      accounting for 76 % of the total costs from 1.85 (95 % CI 1.68, 2.01) million
      fractures. The annual number and costs of osteoporosis-related fractures were
      estimated to double by 2035 and will increase to 5.99 (95 % CI 5.44, 6.55)
      million fractures costing $25.43 (95 % CI 23.92, 26.95) billion by 2050.
      CONCLUSIONS: Our study demonstrated that osteoporosis-related fractures cause a
      substantial economic burden which will markedly increase over the coming decades.
      Consequently, healthcare resource planning must consider these increasing costs,
      and cost-effective screening and intervention policies must urgently be
      identified in an attempt to minimize the impact of fractures on the health of the
      burgeoning population as well as the healthcare budget.

PMID- 25761730
TI  - History-dependent force, angular velocity and muscular endurance in ACTN3
      genotypes.
AB  - PURPOSE: This study aimed at determining the influence of the ACTN3 R577X
      polymorphism on muscle strength and muscle endurance in non-athletic young men.
      METHODS: 266 healthy young men were included in this study. Each subject
      performed maximal isometric, concentric and eccentric contractions of the knee
      extensor muscles on an isokinetic dynamometer. Force depression, force
      enhancement and the fatigue index were derived from these data. In addition,
      handgrip strength, squat jump (SJ) and counter movement jump (CMJ) height were
      obtained. RESULTS: Our group included 83 RR (31 %), 131 RX (49 %) and 52 XX (20
      %) individuals. The muscle bone cross-sectional area of the thigh was 5 % higher
      in RR compared to XX individuals (P = 0.033). RR genotypes showed 6 % higher
      handgrip strength compared to the XX group (P = 0.047). They also jumped 5 %
      higher in both the SJ and CMJ tests (P = 0.029; P = 0.031). No differences were
      found in force depression, force enhancement, isometric or eccentric strength.
      The relative concentric knee torque at 200 degrees /s and at 300 degrees /s was 7
      and 8 % higher in RR compared to XX genotypes, respectively (P = 0.049; P =
      0.048). Also, the fatigue index was found to be 4 % lower in XX genotypes (P =
      0.037). CONCLUSIONS: Our findings are in agreement with the higher prevalence of
      the RR genotype in power-oriented activities. The better fatigue index of XX
      genotypes may be beneficial in endurance-type activities.

PMID- 25761731
TI  - Endurance exercise performance in acute hypoxia is influenced by expiratory flow
      limitation.
AB  - PURPOSE: We sought to determine if expiratory flow limitation influences
      intensive aerobic exercise performance in mild hypoxia. METHODS: Fourteen trained
      male cyclists were separated into flow-limited (FL, n = 7) and non-FL (n = 7)
      groups based on the extent of expiratory flow limitation exhibited during maximal
      exercise in normoxia. Participants performed two self-paced 5-km cycling time
      trials, one in normoxic (F IO2 = 0.21) and one in mild hypoxic (F IO2 = 0.17)
      conditions in a randomized, balanced order with the subjects blinded to
      composition of the inspirate. Percent change from normoxia to hypoxia in average
      power output (%DeltaP TT) and time to completion (%DeltaT TT) were used to assess
      performance. RESULTS: Hypoxia resulted in a significant decline in estimated
      arterial O2 saturation and decrements in performance in both groups, although FL
      had a significantly smaller %DeltaP TT (-4.0 +/- 0.5 vs. -9.0 +/- 1.8 %) and
      %DeltaT TT (1.3 +/- 0.3 vs. 3.7 +/- 0.9 %) compared to non-FL. At the 5th km of
      the time trial, minute ventilation did not change from normoxia to hypoxia in FL
      (3.4 +/- 3.1 %) or non-FL (2.3 +/- 3.7 %), but only the non-FL reported a
      significantly increased dyspnea rating in hypoxia compared to normoxia (~9 %).
      Non-FL athletes did not utilize their ventilatory reserve to defend arterial
      oxygen saturation in hypoxia, which may have been due to an increased measure of
      dyspnea in the hypoxic trial. CONCLUSION: FL athletes experience less hypoxia
      related aerobic exercise performance impairment as compared to non-FL athletes,
      despite having less ventilatory reserve.

PMID- 25761732
TI  - Lung volume and expiratory flow rates from pre- to post-puberty.
AB  - PURPOSE: The purpose was to determine if the airways and lungs grow
      disproportionately from pre- to post-puberty in boys and girls. We hypothesized
      that the airways grow at a slower rate than lung volume (i.e. dysanapsis growth)
      during puberty and boys would exhibit more dysanaptic growth compared to girls.
      METHODS: Twenty-one pre-pubescent children [11 boys (pre 10.1 +/- 0.5 years, post
      15.3 +/- 0.5 years); 10 girls (pre 9.4 +/- 1.0 years, post 14.1 +/- 1.0 years)]
      performed pulmonary function tests (PFTs) ~5 years ago from an original cohort of
      40 children. These 21 children performed PFTs, which included forced vital
      capacity (FVC) and forced expiratory flow at 50 % FVC (FEF50). Static pressure at
      50 % of FVC [Pst(L)50 %] was estimated based on age. Dysanapsis ratio (DR) was
      calculated [FEF50 * FVC(-1) * Pst(L) 50 % (-1) ]. Maturation status was
      determined via Tanner stages. RESULTS: Stage of maturation was not different (p >
      0.05) between boys and girls (4.2 +/- 0.6 stage vs. 3.7 +/- 0.7 stage,
      respectively). FVC and FEF50 increased (p < 0.05), DR significantly decreased,
      and FEF50/FVC was similar (p > 0.05) from pre- to post-puberty. FEF50 and FVC
      significantly increased and DR decreased (p < 0.05) post-puberty for both sexes.
      Post-puberty, boys had a significantly larger FVC, but FEF50, DR, and FEF50/FVC
      were not different (p > 0.05) compared to girls. CONCLUSIONS: These data suggest
      that dysanaptic growth occurs during puberty and that it is not different between
      boys and girls.

PMID- 25761733
TI  - Cardiorespiratory alterations induced by low-intensity exercise performed in
      water or on land.
AB  - The aim of this study was to compare the cardiorespiratory alterations induced by
      a low-intensity exercise performed on land or in water. Sixteen healthy subjects
      were investigated. The exercise consisted of a 1-h period of ergocycling at 35%
      40% of peak oxygen uptake. Investigations were performed at rest and 45 min after
      the beginning of the exercises. Hemodynamic changes were studied by Doppler
      echocardiography. Gas exchanges were continuously monitored by an oxygen gas
      analyzer. Blood samples were taken successively at baseline, within the last
      minutes of the exercise bout, and during recovery to measure total protein
      concentration and natriuretic peptides. Cardiovascular parameters were not
      significantly different during exercise performed on land or in water. As a
      result of an accelerated breathing frequency, ventilation output was
      significantly greater in water. Biological changes included a decrease in total
      protein concentration and an increase in natriuretic peptides in water. During
      low-intensity exercise, ventilatory alterations favoured increasing the work of
      breathing while in the water when compared with the same exercise performed on
      land. Hemodynamic changes were similar in the 2 conditions. Furthermore,
      biological findings suggest that the fluid transfer from intravascular sector
      toward interstitial sector could be facilitated in water. 

PMID- 25761735
TI  - The ACTN3 R577X genotype is associated with muscle function in a Japanese
      population.
AB  - Homozygosity for the common nonsense polymorphism R577X in the alpha-actinin-3
      gene (ACTN3) causes complete alpha-actinin-3 deficiency in fast-twitch skeletal
      muscle fibers. This study investigated whether the ACTN3 R577X polymorphism
      affects fitness status using a battery of tests in a large Japanese cohort. In
      the present study, 1227 subjects (age: 25-85 years) were genotyped for the ACTN3
      R577X polymorphism (rs1815739) using a TaqMan SNP genotyping assay (Applied
      Biosystems). All subjects were divided into 2 groups based on their age (<55
      years and >=55 years). All subjects completed a questionnaire about exercise
      habits and were subjected to a battery of tests to assess their fitness status
      (including grip strength test, chair stand test, and 8-foot walking test). A
      significant association between the ACTN3 R577X genotype and chair stand test
      performance was observed in the group of men >=55 using ANCOVA adjusted for age
      and exercise habits (p = 0.036). The ACTN3 R577X genotype accounted for 2.5% of
      the variability in the results of the chair stand test among men in the >=55 age
      group. Moreover, for the >=55 age group, performance in the chair stand test was
      lower among those with the XX genotype than among those with the RR genotype (p =
      0.024) or RX genotype (p = 0.005), unlike results for the <55 age group. No
      significant difference was noted for hand grip strength or 8-foot walking time.
      Thus, our results suggest that the ACTN3 R577X genotype is associated with lower
      extremity muscle function in the Japanese population. 

PMID- 25761734
TI  - Vitamin E and vitamin C do not reduce insulin sensitivity but inhibit
      mitochondrial protein expression in exercising obese rats.
AB  - Controversy exists as to whether supplementation with the antioxidants vitamin E
      and vitamin C blocks adaptation to exercise. Exercise is a first-line means to
      treat obesity and its complications. While diet-induced obesity alters
      mitochondrial function and induces insulin resistance (IR), no data exist as to
      whether supplementation with vitamin E and vitamin C modify responses to exercise
      in pre-existing obesity. We tested the hypothesis that dietary supplementation
      with vitamin E (0.4 g alpha-tocopherol acetate/kg) and vitamin C (0.5 g/kg)
      blocks exercise-induced improvements on IR and mitochondrial content in obese
      rats maintained on a high-fat (45% fat energy (en)) diet. Diet-induced obese,
      sedentary rats had a 2-fold higher homeostasis model assessment of insulin
      resistance and larger insulin area under the curve following glucose tolerances
      test than rats fed a low-fat (10% fat en) diet. Exercising (12 weeks at 5 times
      per week in a motorized wheel) of obese rats normalized IR indices, an effect not
      modified by vitamin E and vitamin C. Vitamin E and vitamin C supplementation with
      exercise elevated mtDNA content in adipose and skeletal muscle to a greater
      extent (20%) than exercise alone in a depot-specific manner. On the other hand,
      vitamin C and vitamin E decreased exercise-induced increases in mitochondrial
      protein content for complex I (40%) and nicotinamide nucleotide transhydrogenase
      (35%) in a muscle-dependent manner. These data indicate that vitamin E and
      vitamin C supplementation in obese rodents does not modify exercise-induced
      improvements in insulin sensitivity but that changes in mitochondrial biogenesis
      and mitochondrial protein expression may be modified by antioxidant
      supplementation. 

PMID- 25761736
TI  - Multiparametric ultrasound in the detection of prostate cancer: a systematic
      review.
AB  - PURPOSE: To investigate the advances and clinical results of the different
      ultrasound modalities and the progress in combining them into multiparametric
      UltraSound (mpUS). METHODS: A systematic literature search on mpUS and the
      different ultrasound modalities included: greyscale ultrasound, computerized
      transrectal ultrasound, Doppler and power Doppler techniques, dynamic contrast
      enhanced ultrasound and (shear wave) elastography. RESULTS: Limited research
      available on combining ultrasound modalities has presented improvement in
      diagnostic performance. The data of two studies suggest that even adding a lower
      performing ultrasound modality to a better performing modality using crude
      methods can already improve the sensitivity by 13-51 %. The different modalities
      detect different tumours. No study has tried to combine ultrasound modalities
      employing a system similar to the PIRADS system used for mpMRI or more advanced
      classifying algorithms. CONCLUSION: Available evidence confirms that combining
      different ultrasound modalities significantly improves diagnostic performance.

PMID- 25761737
TI  - The effect of urologist experience on choosing active surveillance for prostate
      cancer.
AB  - PURPOSE: To evaluate the impact of the urologist's experience in selecting active
      surveillance (AS) versus immediate treatment (IT) for low-risk prostate cancer.
      METHODS: Men with low-risk prostate cancer were enrolled from March 2011 to
      August 2013 at 13 medical centers in Kaiser Permanente Southern California. The
      AS cohort was defined as men who had cT1-T2a stage prostate cancer, prostate
      specific antigen <10 ng/ml, a biopsy revealing Gleason grade <=6, fewer than
      three biopsy cores positive, <=50 % cancer in any core, and not undergone
      immediate therapy (surgery, radiation, other) within 6 months following
      diagnosis. The urologist's experience (age, number of years in practice, number
      of robotic surgeries performed, and fellowship experience in oncology and/or
      robotics) was then compared between AS and IT cohorts. RESULTS: A total of 4754
      men were diagnosed with prostate cancer, and 713 men satisfied with inclusion
      criteria; 433 (60.7 %) and 280 (39.3 %) chose AS and IT, respectively. A total of
      87 urologists were included. Univariate and multivariate adjusted analyses
      revealed no differences in urologist's age or years in practice. Patients who saw
      urologists who had performed >=50 robotic surgeries were less likely to choose AS
      (OR 0.40, 95 % CI 0.25-0.66). Patients who saw urologists with a fellowship in
      oncology and/or robotics were more than twice as likely to choose AS (OR 2.27, 95
      % CI 1.38-3.75). CONCLUSION: These data suggest that the decision to pursue AS
      may be influenced by the urologist's experience.

PMID- 25761738
TI  - Patterning of magnetic thin films and multilayers using nanostructured tantalum
      gettering templates.
AB  - This work demonstrates that a nonmagnetic thin film of cobalt oxide (CoO)
      sandwiched between Ta seed and capping layers can be effectively reduced to a
      magnetic cobalt thin film by annealing at 200  degrees C, whereas CoO does not
      exhibit ferromagnetic properties at room temperature and is stable at up to ~400 
      degrees C. The CoO reduction is attributed to the thermodynamically driven
      gettering of oxygen by tantalum, similar to the exothermic reduction-oxidation
      reaction observed in thermite systems. Similarly, annealing at 200  degrees C of
      a nonmagnetic [CoO/Pd]N multilayer thin film sandwiched between Ta seed and Ta
      capping layers results in the conversion into a magnetic [Co/Pd]N multilayer, a
      material with perpendicular magnetic anisotropy that is of interest for magnetic
      data storage applications. A nanopatterning approach is introduced where
      [CoO/Pd]N multilayers is locally reduced into [Co/Pd]N multilayers to achieve
      perpendicular magnetic anisotropy nanostructured array. This technique can
      potentially be adapted to nanoscale patterning of other systems for which
      thermodynamically favorable combination of oxide and gettering layers can be
      identified. 

PMID- 25761740
TI  - Preparation and evaluation of monoclonal antibodies against chlamydial protease
      like activity factor to detect Chlamydia pneumoniae antigen in early pediatric
      pneumonia.
AB  - Chlamydia pneumoniae causes diseases in humans, including community-acquired
      pneumonia, bronchitis, and sinusitis. It is also associated with atherosclerosis,
      coronary heart disease, and hyperlipidemia. In this study, we investigated novel
      materials with which to develop a sensitive and specific method to identify early
      C. pneumoniae infection, to allow more effective clinical treatment and
      prevention. We prepared novel monoclonal antibodies (mAbs) against a recombinant
      protein equivalent to the immunodominant region of chlamydial protease-like
      activity factor (CPAF) from C. pneumoniae. The mAbs specifically reacted with the
      endogenous CPAF antigen of the C. pneumoniae type strain in immunoblotting and
      indirect immunofluorescence (IIF) assays, but did not react with C. trachomatis
      type strains or genital secretions from patients with acute C. trachomatis
      infection. The mAb with the highest titer was used to develop a new IIF assay and
      enzyme-linked immunosorbent assay (ELISA) to detect the C. pneumoniae antigen in
      clinical specimens from child patients suspected of pneumonia. The sensitivity,
      specificity, and concordance rate of the mAb-based IIF and ELISA tests were
      compared with those of polymerase chain reaction (PCR). Our results show that
      these mAbs have excellent specificity and may be used to develop new screening
      tools for the diagnosis of early pediatric pneumonia. 

PMID- 25761739
TI  - Infection risk in patients on multiple sclerosis therapeutics.
AB  - The interface of multiple sclerosis (MS) and infection occurs on several levels.
      First, infectious disease has been postulated as a potential trigger, if not
      cause, of MS. Second, exacerbation of MS has been well-documented as a
      consequence of infection, and, lastly, infectious diseases have been recognized
      as a complication of the therapies currently employed in the treatment of MS. MS
      is a disease in which immune dysregulation is a key component. Examination of
      central nervous system (CNS) tissue of people affected by MS demonstrates immune
      cell infiltration, activation and inflammation. Therapies that alter the immune
      response have demonstrated efficacy in reducing relapse rates and evidence of
      brain inflammation on magnetic resonance imaging (MRI). Despite the altered
      immune response in MS, there is a lack of evidence that these patients are at
      increased risk of infectious disease in the absence of treatment or debility.
      Links between infections and disease-modifying therapies (DMTs) used in MS will
      be discussed in this review, as well as estimates of occurrence and ways to
      potentially minimize these risks. We address infection in MS in a comprehensive
      fashion, including (1) the impact of infections on relapse rates in patients with
      MS; (2) a review of available infection data from pivotal trials and
      postmarketing studies for the approved and experimental DMTs, including
      frequency, types and severity of infections; and (3) relevant risk minimization
      strategies, particularly as they pertain to progressive multifocal
      leukoencephalopathy (PML). 

PMID- 25761741
TI  - Study of the diversity and short-chain fatty acids production by the bacterial
      community in overweight and obese Mexican children.
AB  - Obesity and overweight are health problems of multifactorial etiology, which may
      include changes in the microbiome. In Mexico, more than 30 % of the child
      population between 5 and 11 years of age suffer from being overweight or are
      obese, which makes it a public health issue in progress. The purpose of this work
      was to measure the short-chain fatty acid concentration by high-performance
      liquid chromatography (HPLC), and to characterize the bacterial diversity by ion
      torrent semiconductor sequencing, of 16S rDNA libraries prepared from stools
      collected from a sample of well-characterized Mexican children for normal weight,
      overweight, and obese conditions by anthropometric and biochemical criteria. We
      found that triglyceride levels are increased in overweight and obese children,
      who presented altered propionic and butyric acid concentrations in feces. In
      addition, although the colon microbiota did not show a clear bacterial dysbiosis
      among the three conditions, the abundance of some particular bacteria was changed
      with respect to normal controls. We conclude from our results that the imbalance
      in the abundance of at least nine different bacteria as well as altered short
      chain fatty acid concentration in feces is associated to the overweight and obese
      conditions of Mexican children. 

PMID- 25761742
TI  - Hyperuricemia is associated with progression of IgA nephropathy.
AB  - BACKGROUND AND AIM: IgA nephropathy (IgAN) is one of the world's most common
      glomerular diseases. Hyperuricemia was recently defined as risk factor for
      chronic kidney disease. We aimed to investigate the impact of baseline serum uric
      acid levels on progression of IgAN. MATERIALS AND METHODS: A total of 93 patients
      with IgAN were screened. Demographic information and biochemical data were
      recorded. eGFR (using the CKD-EPI = Chronic Kidney Disease Epidemiology
      Collaboration formula) was used as renal function marker. Baseline and sixth
      month eGFR values were calculated. Progression of renal disease was defined as
      the difference between baseline eGFR and sixth month eGFR (delta eGFR). RESULTS:
      Mean age of the patients was 40 +/- 11 years (60% were males). Baseline mean eGFR
      was 77.9 +/- 30.2 mL/min, and baseline mean serum uric acid was 5.65 +/- 1.68
      mg/dL. Importantly, baseline serum uric acid levels were found to be associated
      with the change in eGFR (r = 0.252, p = 0.01). In multivariate analysis (adjusted
      R(2) = 0.171, p = 0.031), adjusting for age, gender, baseline eGFR, blood
      pressure, baseline albumin concentration and ACEI and/or ARB use revealed that
      the baseline serum uric acid levels significantly predicted the change in eGFR.
      CONCLUSION: Baseline serum uric acid concentration is directly proportional to
      the rate of decline in renal functions in patients with IgAN. Uric acid-lowering
      treatments may be beneficial for the prevention of progression of IgAN. However,
      randomized controlled studies are needed for this purpose.

PMID- 25761743
TI  - Efficacy and safety of pirarubicin combined with hyaluronic acid for non-muscle
      invasive bladder cancer after transurethral resection: a prospective, randomized
      study.
AB  - OBJECTIVE: To verify the efficacy and safety of intravesical instillation of
      pirarubicin combined with hyaluronic acid after TURBT in non-muscle invasive
      bladder cancer patients. METHODS: We conducted a prospective study recruiting 127
      eligible patients from 2008 to 2010. Patients were randomly assigned to Group A
      (pirarubicin combined with hyaluronic acid) and Group B (pirarubicin alone).
      Patients' demographics, treatment efficacy on recurrence, visual analog scale
      score, and postoperative complications were evaluated and analyzed during
      observation. RESULTS: After the first month of intravesical chemotherapy, a
      perceptible relief of pelvic pain and urinary symptoms was detectable in Group A
      when compared with Group B (Fig. 2; P = 0.04). From objective analysis, the
      clinicians observed a consistent better improvement in Group A than in Group B on
      clinical conditions (P = 0.02). Frequency, urgency, and odynuria are relieved
      effectively in Group A (21/64 32.9%) and in Group B (41/63 65.1%), with
      significant difference observed (P = 0.001). No statistical evidence of benefit
      was observed in terms of recurrence. No obvious hyaluronic acid-related adverse
      event was observed. CONCLUSIONS: As compared to intravesical instillation of
      pirarubicin alone, the administration of pirarubicin combined with HA for
      prevention from postoperative recurrence was satisfactory and safe. The relief of
      pelvic pain and urinary symptoms is more rapid and more durable.

PMID- 25761744
TI  - Granger causality-based synaptic weights estimation for analyzing neuronal
      networks.
AB  - Granger causality (GC) analysis has emerged as a powerful analytical method for
      estimating the causal relationship among various types of neural activity data.
      However, two problems remain not very clear and further researches are needed:
      (1) The GC measure is designed to be nonnegative in its original form, lacking of
      the trait for differentiating the effects of excitations and inhibitions between
      neurons. (2) How is the estimated causality related to the underlying synaptic
      weights? Based on the GC, we propose a computational algorithm under a best
      linear predictor assumption for analyzing neuronal networks by estimating the
      synaptic weights among them. Under this assumption, the GC analysis can be
      extended to measure both excitatory and inhibitory effects between neurons. The
      method was examined by three sorts of simulated networks: those with linear,
      almost linear, and nonlinear network structures. The method was also illustrated
      to analyze real spike train data from the anterior cingulate cortex (ACC) and the
      striatum (STR). The results showed, under the quinpirole administration, the
      significant existence of excitatory effects inside the ACC, excitatory effects
      from the ACC to the STR, and inhibitory effects inside the STR. 

PMID- 25761745
TI  - Usability of prostaglandin monotherapy eye droppers.
AB  - AIM: To determine the force needed to extract a drop from a range of current
      prostaglandin monotherapy eye droppers and how this related to the comfortable
      and maximum pressure subjects could exert. METHODS: The comfortable and maximum
      pressure subjects could apply to an eye dropper constructed around a set of
      cantilevered pressure sensors and mounted above their eye was assessed in 102
      subjects (mean 51.2+/-18.7 years), repeated three times. A load cell amplifier,
      mounted on a stepper motor controlled linear slide, was constructed and
      calibrated to test the force required to extract the first three drops from 13
      multidose or unidose latanoprost medication eye droppers. RESULTS: The pressure
      that could be exerted on a dropper comfortably (25.9+/-17.7 Newtons, range 1.2
      87.4) could be exceeded with effort (to 64.8+/-27.1 Newtons, range 19.9-157.8;
      F=19.045, p<0.001), and did not differ between repeats (F=0.609, p=0.545).
      Comfortable and maximum pressures exerted were correlated (r=0.618, p<0.001),
      neither were influenced strongly by age (r=0.138, p=0.168; r=-0.118, p=0237,
      respectively), but were lower in women than in men (F=12.757, p=0.001). The force
      required to expel a drop differed between dropper designs (F=22.528, p<0.001),
      ranging from 6.4 Newtons to 23.4 Newtons. The force needed to exert successive
      drops increased (F=36.373, p<0.001) and storing droppers in the fridge further
      increased the force required (F=7.987, p=0.009). CONCLUSIONS: Prostaglandin
      monotherapy droppers for glaucoma treatment vary in their resistance to extract a
      drop and with some a drop could not be comfortably achieved by half the
      population, which may affect compliance and efficacy.

PMID- 25761746
TI  - Late in-the-bag intraocular lens dislocation in patients with uveitis.
AB  - BACKGROUND: Late in-the-bag intraocular lens (IOL) dislocation is an unusual
      complication of cataract surgery, being strongly associated with
      pseudoexfoliation, less so with previous vitreoretinal surgery, myopia and
      uveitis. We present the clinical features, management and outcomes of late
      spontaneous IOL dislocation in a series of patients with uveitis. METHODS: A
      retrospective case series of IOL dislocation affecting patients in the Manchester
      Uveitis Clinic, UK. The uveitis diagnosis, IOL type, presentation and management
      are discussed. RESULTS: Six patients from out of 1056 undergoing cataract surgery
      (0.57%) were affected. Uveitis was the only identified risk factor for IOL
      dislocation, which occurred a mean 10.3 years following uncomplicated cataract
      surgery by phakoemulsification with endocapsular IOL implantation. The
      dislocation was in-the-bag in all six cases. Two patients presented with the IOL
      in the anterior chamber, and required removal of the IOL-bag complex, and are
      using aphakic refractive correction. Two patients with inferior IOL subluxation
      have been managed conservatively. Two patients underwent pars plana vitrectomy
      with sutureless scleral fixation of the existing IOL in one case, and IOL
      exchange with a scleral sutured IOL in the other. CONCLUSIONS: IOL dislocation is
      an uncommon late complication in patients with uveitis. Conservative management
      is appropriate in patients with tolerable symptoms, or in those with difficult
      uveitis. Otherwise, fixation of the existing IOL, or removal and implantation of
      a secondary IOL, may be necessary. Angle-supported, or iris-enclaved IOLs, are
      not of proven safety in this patient group; scleral-fixated posterior chamber
      IOLs are the favoured approach in our service.

PMID- 25761748
TI  - Contributions of community psychology to rural advisory services: an analysis of
      Latin American rural extensionists' point of view.
AB  - During the last decade, rural extension has received interest as being a key tool
      for rural development. Despite rural extension being affected by many
      psychosocial processes, psychology has made scarce contributions to it. An
      investigation was conducted with the aim of gaining knowledge of rural
      extensionists' expectations of psychology, as well as to contribute to shaping
      community psychologists' role in the context of rural extension . 652
      extensionists from 12 Latin American countries were surveyed. The survey included
      closed socio-demographic questions as well as open ones addressing extension
      practice and psychologists' potential contributions. 90.6 % of surveyed
      extensionists considered psychology could help them improve their practice. Most
      mentioned areas of contribution go in line with community psychology, including
      managing farmers groups, facilitating participatory processes and training
      extensionists; while others, such as the expectation of changing farmers' mindset
      and increasing the adoption of external technologies, go against its principles.
      Thus, in some cases, extensionists' expectations could help generate an
      interesting interaction between community psychology and rural extension, while
      in others, they need to be put up for discussion. In brief, community psychology
      has the potential to contribute to rural extension, but it needs to acknowledge
      extension practice as an interesting area for intervention.

PMID- 25761747
TI  - CI-988 Inhibits EGFR Transactivation and Proliferation Caused by Addition of
      CCK/Gastrin to Lung Cancer Cells.
AB  - Cholecystokinin (CCK) receptors are G-protein coupled receptors (GPCR) which are
      present on lung cancer cells. CCK-8 stimulates the proliferation of lung cancer
      cells, whereas the CCK2R receptor antagonist CI-988 inhibits proliferation. GPCR
      for some gastrointestinal hormones/neurotransmitters mediate lung cancer growth
      by causing epidermal growth factor receptor (EGFR) transactivation. Here, the
      role of CCK/gastrin and CI-988 on EGFR transactivation and lung cancer
      proliferation was investigated. Addition of CCK-8 or gastrin-17 (100 nM) to NCI
      H727 human lung cancer cells increased EGFR Tyr(1068) phosphorylation after 2
      min. The ability of CCK-8 to cause EGFR tyrosine phosphorylation was blocked by
      CI-988, gefitinib (EGFR tyrosine kinase inhibitor), PP2 (Src inhibitor), GM6001
      (matrix metalloprotease inhibitor), and tiron (superoxide scavenger). CCK-8
      nonsulfated and gastrin-17 caused EGFR transactivation and bound with high
      affinity to NCI-H727 cells, suggesting that the CCK2R is present. CI-988
      inhibited the ability of CCK-8 to cause ERK phosphorylation and elevate cytosolic
      Ca(2+). CI-988 or gefitinib inhibited the basal growth of NCI-H727 cells or that
      stimulated by CCK-8. The results indicate that CCK/gastrin may increase lung
      cancer proliferation in an EGFR-dependent manner.

PMID- 25761749
TI  - Genome sequence of Trichoderma virens FT-333 from tropical marine climate.
AB  - Environmental factors can cause changes in the content of the fungal genome
      during evolution. In this study, a fungus used as a biocontrol agent, Trichoderma
      virens FT-333 (from a tropical marine climate) has been isolated. The genome
      (38.6 Mbp; GC content, 49.43%) has a total of 12,751 proteins. Gene ontology
      terms (cellular component and molecular function) and KEGG analyses demonstrated
      the importance of the secretion function in FT-333. Compared to the other
      Trichoderma species, copy number of genes related to defense and nutrient
      utilization was variable.

PMID- 25761750
TI  - Synthesis of poly(3-hydroxybutyrate-co-3-hydroxyvalerate) from unrelated carbon
      sources in engineered Rhodospirillum rubrum.
AB  - Different genes encoding pyridine nucleotide transhydrogenases (pntAB, udhA) and
      acetoacetyl-CoA reductases (phaB) were heterologously overexpressed in
      Rhodospirillum rubrum S1. A recombinant strain, which harbored the gene encoding
      the membrane-bound transhydrogenase PntAB from Escherichia coli MG1655 and the
      phaB1 gene coding for an NADPH-dependent acetoacetyl-CoA reductase from Ralstonia
      eutropha H16, accumulated poly(3-hydroxybutyrate-co-3-hydroxyvalerate) [Poly(3HB
      co-3HV)] with a 3HV fraction of up to 13 mol% from fructose. This was a 13-fold
      increase of the 3HV content when compared to the wild-type strain. Higher
      contents of 3HV are known to reduce the brittleness of this polymer, which is
      advantageous for most applications. The engineered R. rubrum strain was also able
      to synthesize this industrially relevant copolymer from CO2 and CO from
      artificial synthesis gas (syngas) with a 3HV content of 56 mol%. The increased
      incorporation of 3HV was attributed to an excess of propionyl-CoA, which was
      generated from threonine and related amino acids to compensate for the
      intracellular redox imbalance resulting from the transhydrogenase reaction.
      Thereby, our study presents a novel, molecular approach to alter the composition
      of bacterial PHAs independently from external precursor supply. Moreover, this
      study also provides a promising production strain for syngas-derived second
      generation biopolymers. 

PMID- 25761751
TI  - Genome sequence of a clinical isolate of dermatophyte, Trichophyton rubrum from
      India.
AB  - Trichophyton rubrum is one of the major causative agents of dermatophytosis in
      humans worldwide. We report the draft genome sequence of T. rubrum var.
      raubitschekii from Delhi, India, isolated from a patient presenting symptoms of
      onychomycosis. The total estimated genome size of the clinical isolate is 25.2 MB
      containing 8265 predicted protein-coding sequences, 91 tRNA and 15 rRNA genes.
      Sequence analysis of the secreted subtilases, one of the major virulence factors
      in dermatophytes, clusters them into three subfamilies with distinct sequence
      features. The genome sequence is a step in understanding diversity of
      dermatophytes worldwide and will aid in identification of virulence factors and
      dissecting mechanisms of pathogenesis among them. 

PMID- 25761752
TI  - Cloning and identification of a novel tyrosinase and its overexpression in
      Streptomyces kathirae SC-1 for enhancing melanin production.
AB  - A 30-kDa novel tyrosinase was purified to homogeneity. The Km for L-Dopa and L
      tyrosine were determined as 0.42 and 0.25 mM. The 1231 bp (base pair) melC gene
      and its 167 bp promoter Pskmel were obtained by thermal asymmetric interlaced
      polymerase chain reaction based on the amino acids fragment obtained from MS
      results of the purified enzyme. The protein sequence of tyrosinase shows maximum
      identity (84%) to tyrosinase from Streptomyces galbus. The melC was introduced
      into S. kathirae. The melanin production and the transcriptional level of melC in
      recombinant S. kathirae [pIJPskmelmelC] were about 2.1-fold and 2-fold higher
      than the wild-type strain, respectively. The melanin concentration was maximized
      at 28.8 g L(-1). 

PMID- 25761753
TI  - Draft genomic DNA sequence of the multi-resistant Sphingomonas sp. strain AntH11
      isolated from an Antarctic hypolith.
AB  - Hypoliths are microbial communities that live underneath translucent rocks in
      desert ecosystems and represent a key refuge niche in the Antarctic Dry Valleys.
      These cryptic microbial assemblages are crucial as they mediate numerous
      ecosystem processes. Here, we present the first draft genome of a hypolith
      isolate belonging to the alpha-proteobacterial class and the genus Sphingomonas.
      The draft genome of Sphingomonas sp. strain AntH11 shows the capacity of this
      organism to adapt to the extreme cold and arid conditions encountered in
      Antarctic desert soils. Our result also suggests that its metabolic versatility
      and multidrug resistance constitutes an opportunistic advantage in competition
      with other hypolith-colonizing microorganisms. 

PMID- 25761754
TI  - Exogenous glycine and serine promote growth and antifungal activity of
      Penicillium citrinum W1 from the south-west Indian Ocean.
AB  - PcPAF is a novel antifungal protein identified by our recent study, which is
      produced by a fungal strain Penicillium citrinum W1 isolated from a south-west
      Indian Ocean sediment sample. The present study identified glycine as a potential
      metabolite which increased the fungal growth and promoted antifungal activity.
      Then, GC/MS based metabolomics was used to disclose the metabolic mechanism
      manipulated by glycine. With the aid of unsupervised hierarchical clustering
      analysis and supervised orthogonal partial least-squares-discriminant analysis,
      the intracellular metabolite profiles were distinguished among two glycine
      treated groups and control. 43 and 47 significantly varied metabolites were
      detected in 2.5 mM or 5 mM glycine-treated groups and involved in seven and eight
      pathways, respectively. Furthermore, exogenous serine, which is converted from
      glycine, showed the same potential as glycine did. Our findings not only identify
      glycine and serine as nutrients which promoted P. citrinum W1 growth and
      increased antifungal activity, but also highlight the way to utilize metabolomics
      for an understanding of metabolic mechanism manipulated by an exogenous compound.

PMID- 25761755
TI  - Biochemical characterization of a novel iron-dependent GH16 beta-agarase, AgaH92,
      from an agarolytic bacterium Pseudoalteromonas sp. H9.
AB  - A putative agarase gene (agaH92) encoding a primary translation product (50.1
      kDa) of 445 amino acids with a 19-amino-acid signal peptide and glycoside
      hydrolase 16 and RICIN superfamily domains was identified in an agarolytic marine
      bacterium, Pseudoalteromonas sp. H9 ( = KCTC23887). The heterologously expressed
      protein rAgaH92 in Escherichia coli had an apparent molecular weight of 51 kDa on
      SDS-PAGE, consistent with the calculated molecular weight. Agarase activity of
      rAgaH92 was confirmed by a zymogram assay. rAgaH92 hydrolyzed p-nitrophenyl-beta
      D-galactopyranoside, but not p-nitrophenyl-alpha-D-galactopyranoside. The optimum
      pH and temperature for rAgaH92 were 6.0 and 45 degrees C, respectively. It was
      thermostable and retained more than 85% of its initial activity after heat
      treatment at 50 degrees C for 1 h. rAgaH92 required Fe(2+) for agarase activity
      and inhibition by EDTA was compensated by Fe(2+). TLC analysis, mass spectrometry
      and NMR spectrometry of the GST-AgaH71 hydrolysis products revealed that rAgaH92
      is an endo-type beta-agarase, hydrolyzing agarose into neoagarotetraose and
      neoagarohexaose. 

PMID- 25761756
TI  - Novel role for carbohydrate responsive element binding protein in the control of
      ethanol metabolism and susceptibility to binge drinking.
AB  - Carbohydrate responsive element binding protein (ChREBP) is central for de novo
      fatty acid synthesis under physiological conditions and in the context of
      nonalcoholic fatty liver disease. We explored its contribution to alcohol-induced
      steatosis in a mouse model of binge drinking as acute ethanol (EtOH) intoxication
      has become an alarming health problem. Within 6 hours, ChREBP acetylation and its
      recruitment onto target gene promoters were increased in liver of EtOH-fed mice.
      Acetylation of ChREBP was dependent on alcohol metabolism because inhibition of
      alcohol dehydrogenase (ADH) activity blunted ChREBP EtOH-induced acetylation in
      mouse hepatocytes. Transfection of an acetylation-defective mutant of ChREBP
      (ChREBP(K672A) ) in HepG2 cells impaired the stimulatory effect of EtOH on ChREBP
      activity. Importantly, ChREBP silencing in the liver of EtOH-fed mice prevented
      alcohol-induced triglyceride accumulation through an inhibition of the lipogenic
      pathway but also led, unexpectedly, to hypothermia, increased blood acetaldehyde
      concentrations, and enhanced lethality. This phenotype was associated with
      impaired hepatic EtOH metabolism as a consequence of reduced ADH activity. While
      the expression and activity of the NAD(+) dependent deacetylase sirtuin 1, a
      ChREBP-negative target, were down-regulated in the liver of alcohol-fed mice,
      they were restored to control levels upon ChREBP silencing. In turn, ADH
      acetylation was reduced, suggesting that ChREBP regulates EtOH metabolism and ADH
      activity through its direct control of sirtuin 1 expression. Indeed, when sirtuin
      1 activity was rescued by resveratrol pretreatment in EtOH-treated hepatocytes, a
      significant decrease in ADH protein content and/or acetylation was observed.
      CONCLUSION: our study describes a novel role for ChREBP in EtOH metabolism and
      unravels its protective effect against severe intoxication in response to binge
      drinking.

PMID- 25761757
TI  - Cognitive strategies and quality of life of patients with high-grade glioma.
AB  - The purpose of this study was to analyze the psychological well-being, quality of
      life, and cognitive strategies activated by patients with high-grade glioma. We
      hypothesized that the self-perceived quality of life is modulated by physical and
      psychological factors and that in order to understand this modulation more
      psychometric approaches are necessary. Data were collected from a sample of 73
      consecutive patients with a histological diagnosis of primary malignant brain
      cancer (grade IV glioblastoma and grade III anaplastic astrocytoma) hospitalized
      in a specialized Italian center. The Functional Assessment of Cancer Therapy
      (FACT) scale and the Schedule of Evaluation of Individual Quality of Life-Direct
      Weighting (SEIQoL-DW) scale were used to assess quality of life. The mean FACT
      Brain (Br) score was 122.37. Similarly, the median SEIQoL-DW score was 72.9 out
      of a maximum value of 100. No gender effect was found in relation to overall
      quality of life. Patients with high depression and/or anxiety scores reported
      lower quality of life (QoL) scores in all the instruments considered. We did not
      find any gender effect concerning depression and anxiety levels. However, we
      found that men and women, though having similar physical and functional well
      being, reported different QoL determinants, since men seem to rely more on
      physical adjustment, while women activate more introspective strategies. Positive
      actions, family issues, negative thoughts, health, and positive thoughts were
      found to be the most reported themes. In conclusion, the present study strongly
      suggests that a positive psychological adjustment is possible also in the event
      of a severe diagnosis and during aggressive treatments, but QoL determinants
      might be considered too in order to help health professionals to understand
      patients' experience and to meet their needs. 

PMID- 25761758
TI  - Intraductal tubulopapillary neoplasm of the pancreatic branch duct showing
      atypical images.

PMID- 25761759
TI  - Investigating the dependence of the calibration parameter M on echo time.
AB  - PURPOSE: The calculation of the calibration parameter M, which represents the
      maximum theoretically possible blood oxygen level dependent (BOLD) signal
      increase, is an essential intermediate step in any calibrated fMRI experiment. To
      better compare M values obtained across different studies, it is common to scale
      M values from their original BOLD echo time (TE) to a different echo time
      according to the theory that M is directly proportional to TE. To the best of our
      knowledge, this relationship has never been directly tested. THEORY AND METHODS:
      A pseudocontinuous arterial spin labeling sequence with five readouts (TE ranging
      from 20 to 78 ms) was implemented to test the relationship between M and TE, both
      with and without the application of flow crushing gradients. RESULTS: Both M and
      the BOLD signal were found to be linear functions of TE, but with a nonzero
      intercept. This intercept was reduced when crusher gradients were added,
      suggesting that the deviation from theory is a result of nonnegligible
      intravascular signal. CONCLUSION: The linear scaling method introduces some error
      when comparing M values acquired with different BOLD echo times. However, this
      error is small compared with other considerations, and would generally not
      preclude the continued use of this scaling method.

PMID- 25761761
TI  - Growing and evolving: remarks for the 35(th) anniversary of the founding of
      Zoological Research.

PMID- 25761760
TI  - Topology of Endoplasmic Reticulum-Associated Cellular and Viral Proteins
      Determined with Split-GFP.
AB  - The split green fluorescent protein (GFP) system was adapted for investigation of
      the topology of ER-associated proteins. A 215-amino acid fragment of GFP (S1-10)
      was expressed in the cytoplasm as a free protein or fused to the N-terminus of
      calnexin and in the ER as an intraluminal protein or fused to the C-terminus of
      calnexin. A 16-amino acid fragment of GFP (S11) was fused to the N- or C-terminus
      of the target protein. Fluorescence occurred when both GFP fragments were in the
      same intracellular compartment. After validation with the cellular proteins PDI
      and tapasin, we investigated two vaccinia virus proteins (L2 and A30.5) of
      unknown topology that localize to the ER and are required for assembly of the
      viral membrane. Our results indicated that the N- and C-termini of L2 faced the
      cytoplasmic and luminal sides of the ER, respectively. In contrast both the N-
      and C-termini of A30.5 faced the cytoplasm. The system offers advantages for
      quickly determining the topology of intracellular proteins: the S11 tag is
      similar in length to commonly used epitope tags; multiple options are available
      for detecting fluorescence in live or fixed cells; transfection protocols are
      adaptable to numerous expression systems and can enable high throughput
      applications. 

PMID- 25761762
TI  - The dependence of efficiency of transmembrane molecular transfer using
      electroporation on medium viscosity.
AB  - BACKGROUND: In the present study, we aimed to evaluate the efficiency of drug and
      gene electrotransfer into cells in vitro depending on medium viscosity. METHODS:
      Experiments were performed using Chinese hamster ovary cells. Efficiency of
      molecular electrotransfer depending of medium viscosity was evaluated using two
      different electroporation conditions: a high-voltage (HV) pulse and a combination
      of a high-voltage pulse and a low-voltage pulse (HV + LV). To evaluate the
      efficiency of molecular electrotransfer, anticancer drug bleomycin and two
      different plasmids coding for green fluorescent protein and luciferase were used.
      RESULTS: We found that a slight increase in medium viscosity from 1.3-1.4 mPa.s
      significantly decreased the transfection efficiency, both in terms of transfected
      cells and total protein production, which was abolished completely with an
      increase in medium viscosity to 6.1 mPa.s. Notably, at this medium viscosity,
      electrotransfer of the small anticancer drug was still efficient. Using HV and HV
      + LV pulse combinations, we showed that a decrease of DNA electrotransfer,
      especially at lower medium viscosities, can be compensated for by the LV pulse to
      some extent. On the other hand, the addition of the LV pulse after the HV pulse
      did not have any positive effect on the efficiency of bleomycin electrotransfer.
      CONCLUSIONS: These findings demonstrate that transfection is very susceptible to
      medium viscosity and highlights the importance of the electrophoretic component
      in experiments when a considerable transfection level is needed.

PMID- 25761763
TI  - Coverage of Skin Cancer Risk Factors and UV Behaviors in Popular U.S. Magazines
      from 2000 to 2012.
AB  - Mass media is an influential source of skin cancer and tanning information for
      the public, but we know little about its content or emphasis. The objective of
      this research was to describe the volume and nature of skin cancer and tanning
      messages in 20 popular U.S. men's and women's magazines (2000-2012). We used a
      directed content analysis to determine frequency information about risk factors
      and ultraviolet (UV) behaviors in 608 articles and 930 images. Chi-square and
      Fisher's exact tests determined coverage differences based on content type (text
      vs. image) and target audience (women vs. men). UV exposure was the most common
      risk factor mentioned (37.7 %) and sunscreen use the most common behavior
      encouraged (60.0 %); information about other risk factors and protective
      behaviors was uncommon. Both articles (25.2 %) and images (36.9 %) promoted the
      tanned look as attractive. In most cases, images infrequently contained helpful
      information on skin cancer risk factors and prevention, except for high-SPF
      sunscreens. Women's magazines published more articles on skin cancer and tanning
      than men's magazines (456 vs. 159, chi(2) = 143.43, P < .01), and the nature of
      the messages differed between them. Magazine skin cancer and tanning content may
      contribute to inaccurate public understanding of risks and prevention. These
      findings are relevant to cancer educators, who may wish to counter potentially
      harmful messages and enhance positive ones through cancer education efforts. 

PMID- 25761764
TI  - Loss of muscleblind-like 1 results in cardiac pathology and persistence of
      embryonic splice isoforms.
AB  - Cardiac dysfunction is a prominent cause of mortality in myotonic dystrophy I
      (DM1), a disease where expanded CUG repeats bind and disable the muscleblind-like
      family of splice regulators. Deletion of muscleblind-like 1
      (Mbnl1(DeltaE2/DeltaE2)) in 129 sv mice results in QRS, QTc widening, bundle
      block and STc narrowing at 2-4 months of age. With time, cardiac function
      deteriorates further and at 6 months, decreased R wave amplitudes, sinus node
      dysfunction, cardiac hypertrophy, interstitial fibrosis, multi-focal myocardial
      fiber death and calcification manifest. Sudden death, where no end point illness
      is overt, is observed at a median age of 6.5 and 4.8 months in ~67% and ~86% of
      male and female Mbnl1(DeltaE2/DeltaE2) mice, respectively. Mbnl1 depletion
      results in the persistence of embryonic splice isoforms in a network of cardiac
      RNAs, some of which have been previously implicated in DM1, regulating sodium and
      calcium currents, Scn5a, Junctin, Junctate, Atp2a1, Atp11a, Cacna1s, Ryr2, intra
      and inter cellular transport, Clta, Stx2, Tjp1, cell survival, Capn3, Sirt2,
      Csda, sarcomere and cytoskeleton organization and function, Trim55, Mapt, Pdlim3,
      Pdlim5, Sorbs1, Sorbs2, Fhod1, Spag9 and structural components of the sarcomere,
      Myom1, Tnnt2, Zasp. Thus this study supports a key role for Mbnl1 loss in the
      initiation of DM1 cardiac disease. 

PMID- 25761765
TI  - The effect of selection environment on the probability of parallel evolution.
AB  - Across the great diversity of life, there are many compelling examples of
      parallel and convergent evolution-similar evolutionary changes arising in
      independently evolving populations. Parallel evolution is often taken to be
      strong evidence of adaptation occurring in populations that are highly
      constrained in their genetic variation. Theoretical models suggest a few
      potential factors driving the probability of parallel evolution, but experimental
      tests are needed. In this study, we quantify the degree of parallel evolution in
      15 replicate populations of Pseudomonas fluorescens evolved in five different
      environments that varied in resource type and arrangement. We identified repeat
      changes across multiple levels of biological organization from phenotype, to
      gene, to nucleotide, and tested the impact of 1) selection environment, 2) the
      degree of adaptation, and 3) the degree of heterogeneity in the environment on
      the degree of parallel evolution at the gene-level. We saw, as expected, that
      parallel evolution occurred more often between populations evolved in the same
      environment; however, the extent of parallel evolution varied widely. The degree
      of adaptation did not significantly explain variation in the extent of
      parallelism in our system but number of available beneficial mutations correlated
      negatively with parallel evolution. In addition, degree of parallel evolution was
      significantly higher in populations evolved in a spatially structured,
      multiresource environment, suggesting that environmental heterogeneity may be an
      important factor constraining adaptation. Overall, our results stress the
      importance of environment in driving parallel evolutionary changes and point to a
      number of avenues for future work for understanding when evolution is
      predictable. 

PMID- 25761766
TI  - U6 snRNA Pseudogenes: Markers of Retrotransposition Dynamics in Mammals.
AB  - Transposable elements comprise more than 45% of the human genome and long
      interspersed nuclear element 1 (LINE-1 or L1) is the only autonomous mobile
      element remaining active. Since its identification, it has been proposed that L1
      contributes to the mobilization and amplification of other cellular RNAs and more
      recently, experimental demonstrations of this function has been described for
      many transcripts such as Alu, a nonautonomous mobile element, cellular mRNAs, or
      small noncoding RNAs. Detailed examination of the mobilization of various
      cellular RNAs revealed distinct pathways by which they could be recruited during
      retrotransposition; template choice or template switching. Here, by analyzing
      genomic structures and retrotransposition signatures associated with small
      nuclear RNA (snRNA) sequences, we identified distinct recruiting steps during the
      L1 retrotransposition cycle for the formation of snRNA-processed pseudogenes.
      Interestingly, some of the identified recruiting steps take place in the nucleus.
      Moreover, after comparison to other vertebrate genomes, we established that snRNA
      amplification by template switching is common to many LINE families from several
      LINE clades. Finally, we suggest that U6 snRNA copies can serve as markers of L1
      retrotransposition dynamics in mammalian genomes. 

PMID- 25761768
TI  - Air displacement plethysmography: cradle to grave.
AB  - Differences in body composition are associated with increased disease risk in
      various stages of life. Despite numerous available methods in assessing body
      composition (air displacement plethysmography, dual-energy X-ray absorptiometry,
      bioelectrical impedance, hydrometry, and magnetic resonance imaging), due to
      innate technical limitations, the ability for one singular method to track body
      composition over the life span (ie, infancy to adulthood) is challenging and
      imperfect. The primary goal of this review is to determine if there are body
      composition methods that can accurately track body composition from infancy into
      adulthood. After careful consideration and taking into account the best available
      scientific evidence, we feel air displacement plethysmography is the best
      instrument at this time for tracking body composition, starting in infancy and
      forward into adulthood, partly because it is the only "practical" clinical tool
      currently available for use during infancy. 

PMID- 25761767
TI  - Protective effects of vascular endothelial growth factor in cultured brain
      endothelial cells against hypoglycemia.
AB  - Hypoglycemia is a common and serious problem among patients with type 1 diabetes
      receiving treatment with insulin. Clinical studies have demonstrated that
      hypoglycemic edema is involved in the initiation of hypoglycemic brain damage.
      However, the mechanisms of this edema are poorly understood. Vascular endothelial
      growth factor (VEGF), a potent regulator of blood vessel function, has been
      observed an important candidate hormone induced by hypoglycemia to protect
      neurons by restoring plasma glucose. Whether VEGF has a protective effect against
      hypoglycemia-induced damage in brain endothelial cells is still unknown. To
      investigate the effects of hypoglycemia on cerebral microvascular endothelial
      cells and assess the protective effect of exogenous VEGF on endothelial cells
      during hypoglycemia, confluent monolayers of the brain endothelial cell line
      bEnd.3 were treated with normal (5.5 mM glucose), hypoglycemic (0, 0.5, 1 mM
      glucose) medium or hypoglycemic medium in the presence of VEGF. The results
      clearly showed that hypoglycemia significantly downregulated the expression of
      claudin-5 in bEnd.3 cells, without affecting ZO-1 and occludin expression and
      distribution. Besides, transendothelial permeability significantly increased
      under hypoglycemic conditions compared to that under control conditions.
      Moreover, the hypoglycemic medium in presence of VEGF decreased endothelial
      permeability via the inhibition of claudin-5 degradation and improved
      hypoglycemia-induced cell toxicity. Furthermore, Glucose transporter-1 (Glut-1)
      and apoptosis regulator Bcl-2 expression were significantly upregulated. Taken
      together, hypoglycemia can significantly increase paraendocellular permeability
      by downregulating claudin-5 expression. We further showed that VEGF protected
      brain endothelial cells against hypoglycemia by enhancing glucose passage,
      reducing endothelial cell death, and ameliorating paraendocellular permeability. 

PMID- 25761769
TI  - Food supplementation among HIV-infected adults in Sub-Saharan Africa: impact on
      treatment adherence and weight gain.
AB  - Sub-Saharan Africa has the highest proportion of undernourished people in the
      world, along with the highest number of people living with HIV and AIDS. Thus, as
      a result of high levels of food insecurity many HIV patients are also
      undernourished. The synergism between HIV and undernutrition leads to poor
      treatment adherence and high mortality rates. Undernutrition has a debilitating
      effect on the immune system due to key nutrient deficiencies and the
      overproduction of reactive species (oxidative stress), which causes rapid HIV
      progression and the onset of AIDS. Therapeutic food supplementation used in the
      treatment of severe acute malnutrition is being applied to HIV palliative care;
      however, little biochemical data exist to highlight its impact on oxidative
      stress and immune recovery. In addition, as most food supplements are imported by
      donor agencies, efforts are being put into local therapeutic food production such
      as the Food Multi-Mix concept to ensure sustainability. The purpose of this
      review is to highlight studies that examine the effectiveness of food
      supplementation in undernourished HIV patients in Sub-Saharan Africa; noting the
      parameters used to measure efficacy, as well as the long-term feasibility of
      supplementation. 

PMID- 25761770
TI  - Response to Villanacci et. al.

PMID- 25761771
TI  - Quercetin and related polyphenols: new insights and implications for their
      bioactivity and bioavailability.
AB  - The physiological functions and bioavailability of flavonoids have been widely
      investigated since their bioactivities were identified about 80 years ago.
      Quercetin is a typical flavonoid ubiquitously contained in vegetables and fruits
      with several biological effects demonstrated in vitro and in vivo including
      antioxidative, anti-inflammatory, anticancer, and antidiabetic activities. After
      the ingestion of vegetables and fruits, quercetin glycosides are metabolized,
      absorbed, and circulated as types of conjugates in the blood. Thereafter,
      quercetin-3-O-beta-D-glucuronide (Q3GA), a major metabolite of quercetin, is
      distributed throughout the body where it may exert beneficial functions in target
      tissues. Hydrophilic Q3GA has been found to be deconjugated into hydrophobic
      quercetin aglycone at injured sites which, in turn, may improve the pathological
      conditions. This review presents updated information on the biological aspects
      and mechanisms of action of quercetin and its related polyphenols. In particular,
      new insights into their beneficial health effects on the brain, blood vessels,
      muscle, and intestine will be discussed.

PMID- 25761773
TI  - Structure-properties relationships in triarylamine-based donor-acceptor molecules
      containing naphtyl groups as donor material for organic solar cells.
AB  - The effects of replacing the phenyl rings of triphenylamine (TPA) by naphtyl
      groups are analysed on a series of push-pull molecules containing a 2-thienyl
      dicyanovinyl acceptor group. UV-Vis absorption spectroscopy and cyclic
      voltammetry show that the introduction of one or two naphtyl groups in the
      structure has limited effects on the optical properties and energy levels of the
      molecule. On the other hand, the evaluation of the compounds as donor material in
      bi-layer solar cells with C60 as acceptor shows that the number and mode of
      linkage of the naphtyl groups exert a marked influence on the power conversion
      efficiency (PCE) of the cell. Two naphtyl groups lead to a decrease of PCE with
      respect to TPA, while a single naphtyl group produces opposite effects depending
      on the linking mode. Compared to TPA, an alpha-naphtyl group leads to a small
      decrease of PCE while in contrast a beta-naphtyl leads to a ~35% increase of PCE
      due to improved short-circuit current density (Jsc) and fill-factor. The
      determination of the hole-mobility of these two donors by the space-charge
      limited current method shows that these effects are correlated with the higher
      hole-mobility of the beta-naphtyl compound. 

PMID- 25761774
TI  - Parasitology, volume 142, issue 1--erratum.

PMID- 25761772
TI  - SOXC Transcription Factors Induce Cartilage Growth Plate Formation in Mouse
      Embryos by Promoting Noncanonical WNT Signaling.
AB  - Growth plates are specialized cartilage structures that ensure the elongation of
      most skeletal primordia during vertebrate development. They are made by
      chondrocytes that proliferate in longitudinal columns and then progress in a
      staggered manner towards prehypertrophic, hypertrophic and terminal maturation.
      Complex molecular networks control the formation and activity of growth plates,
      but remain incompletely understood. We investigated here the importance of the
      SoxC genes, which encode the SOX4, SOX11 and SOX12 transcription factors, in
      growth plates. We show that the three genes are expressed robustly in
      perichondrocytes and weakly in growth plate chondrocytes. SoxC(Prx1Cre) mice,
      which deleted SoxC genes in limb bud skeletogenic mesenchyme, were born with tiny
      appendicular cartilage primordia because of failure to form growth plates. In
      contrast, SoxC(Col2Cre) and SoxC(ATC) mice, which deleted SoxC genes primarily in
      chondrocytes, were born with mild dwarfism and fair growth plates. Chondrocytes
      in the latter mutants matured normally, but formed irregular columns,
      proliferated slowly and died ectopically. Asymmetric distribution of VANGL2 was
      defective in both SoxC(Prx1Cre) and SoxC(ATC) chondrocytes, indicating impairment
      of planar cell polarity, a noncanonical WNT signaling pathway that controls
      growth plate chondrocyte alignment, proliferation and survival. Accordingly, SoxC
      genes were necessary in perichondrocytes for expression of Wnt5a, which encodes a
      noncanonical WNT ligand required for growth plate formation, and in chondrocytes
      and perichondrocytes for expression of Fzd3 and Csnk1e, which encode a WNT
      receptor and casein kinase-1 subunit mediating planar cell polarity,
      respectively. Reflecting the differential strengths of the SOXC protein
      transactivation domains, SOX11 was more powerful than SOX4, and SOX12 interfered
      with the activity of SOX4 and SOX11. Altogether, these findings provide novel
      insights into the molecular regulation of skeletal growth by proposing that SOXC
      proteins act cell- and non-cell-autonomously in perichondrocytes and chondrocytes
      to establish noncanonical WNT signaling crosstalk essential for growth plate
      induction and control.

PMID- 25761775
TI  - Improving self-help e-therapy for depression and anxiety among sexual minorities:
      an analysis of focus groups with lesbians and gay men.
AB  - BACKGROUND: E-therapies for depression and anxiety rarely account for lesbian and
      gay users. This is despite lesbians and gay men being at heightened risk of mood
      disorders and likely to benefit from having access to tailored self-help
      resources. OBJECTIVE: We sought to determine how e-therapies for depression and
      anxiety could be improved to address the therapeutic needs of lesbians and gay
      men. METHODS: We conducted eight focus groups with lesbians and gay men aged 18
      years and older. Focus groups were presented with key modules from the popular e
      therapy "MoodGYM". They were asked to evaluate the inclusiveness and relevance of
      these modules for lesbians and gay men and to think about ways that e-therapies
      in general could be modified. The focus groups were analyzed qualitatively using
      a thematic analysis approach to identify major themes. RESULTS: The focus groups
      indicated that some but not all aspects of MoodGYM were suitable, and suggested
      ways of improving e-therapies for lesbian and gay users. Suggestions included
      avoiding language or examples that assumed or implied users were heterosexual,
      improving inclusiveness by representing non-heterosexual relationships, providing
      referrals to specialized support services and addressing stigma-related stress,
      such as "coming out" and experiences of discrimination and harassment. Focus
      group participants suggested that dedicated e-therapies for lesbians and gay men
      should be developed or general e-therapies be made more inclusive by using
      adaptive logic to deliver content appropriate for a user's sexual identity.
      CONCLUSIONS: Findings from this study offer in-depth guidance for developing e
      therapies that more effectively address mental health problems among lesbians and
      gay men.

PMID- 25761776
TI  - Melt-blown and electrospun drug-loaded polymer fiber mats for dissolution
      enhancement: a comparative study.
AB  - Melt blowing (MB) was investigated to prepare a fast dissolving fibrous drug
      loaded solid dispersion and compared with solvent-based electrospinning (SES) and
      melt electrospinning (MES). As a conventional solvent-free technique coupled with
      melt extrusion and using a high-speed gas stream, MB can provide high-quality
      micro- and nanofibers at industrial throughput levels. Carvedilol, a weak-base
      model drug with poor water solubility, was processed using a common composition
      optimized for the fiber spinning and blowing methods based on a hydrophilic
      vinylpyrrolidone-vinyl acetate copolymer (PVPVA64) and PEG 3000 plasticizer.
      Scanning electron microscopy combined with fiber diameter analysis showed
      diameter distributions characteristic to each prepared fibrous fabrics (the mean
      value increased toward SES<MB<MES). Differential scanning calorimetry and X-ray
      diffraction studies revealed that the incorporated drug was in amorphous form
      regardless the preparation method. The HPLC studies demonstrated that all of the
      materials produced by the different techniques passed the regulatory purity
      requirements. The fibers exhibited ultrafast drug release tested under neutral pH
      conditions; the melt-blown sample dissolved within 2 min owing to its large
      specific surface area. The presented results confirm the applicability of MB as a
      novel formulation technique for polymer-based drug delivery systems.

PMID- 25761777
TI  - PERK silence inhibits glioma cell growth under low glucose stress by blockage of
      p-AKT and subsequent HK2's mitochondria translocation.
AB  - Glioma relies on glycolysis to obtain energy and sustain its survival under low
      glucose microenvironment in vivo. The mechanisms on glioma cell glycolysis
      regulation are still unclear. Signaling mediated by Double-stranded RNA-activated
      protein kinase (PKR) - like ER kinase (PERK) is one of the important pathways of
      unfolded protein response (UPR) which is comprehensively activated in cancer
      cells upon the hypoxic and low glucose stress. Here we show that PERK is
      significantly activated in human glioma tissues. PERK silencing results in
      decreased glioma cell viability and ATP/lactate production upon low glucose
      stress, which is mediated by partially blocked AKT activation and subsequent
      inhibition of Hexokinase II (HK2)'s mitochondria translocation. More importantly,
      PERK silenced glioma cells show decreased tumor formation capacity. Our results
      reveal that PERK activation is involved in glioma glycolysis regulation and may
      be a potential molecular target for glioma treatment. 

PMID- 25761778
TI  - Amphiphilic p-sulfonatocalix[4]arene as "drug chaperone" for escorting anticancer
      drugs.
AB  - Supramolecularly constructing multifunctional platform for drug delivery is a
      challenging task. In this work, we propose a novel supramolecular strategy "drug
      chaperone", in which macrocyclic amphiphiles directly coassemble with cationic
      drugs into a multifunctional platform and its surface is further decorated with
      targeting ligands through host-guest recognition. The coassembling and
      hierarchical decoration processes were monitored by optical transmittance
      measurements, and the size and morphology of amphiphilic coassemblies were
      identified by dynamic light scattering and high-resolution transmission electron
      microscopy. In cell experiments to validate the drug chaperone strategy, the
      anticancer activities of free drugs were pronouncedly improved by coassembling
      with amphiphilic chaperone and further functionalization with targeting ligand. 

PMID- 25761779
TI  - Long-term results of radical cystectomy and role of adjuvant chemotherapy for
      small cell carcinoma of the bladder.
AB  - OBJECTIVE: To review our experience with radical cystectomy for small cell
      carcinoma of the bladder, to compare outcomes with a cohort of patients with
      urothelial carcinoma, and to determine the effect of adjuvant chemotherapy and
      pathology re-review in this setting. METHODS: Among 2427 patients who underwent
      radical cystectomy, 68 patients had small cell carcinoma of the bladder. Patients
      with small cell carcinoma of the bladder were compared with an unmatched cohort
      of 1146 patients with urothelial carcinoma, and were then matched (1:2) based on
      TNM stage. Survival was estimated using the Kaplan-Meier method, and Cox models
      were used to evaluate association of clinicopathological features with outcome.
      RESULTS: Among the 68 small cell carcinoma of the bladder patients, 37 (54%) were
      found to have small cell carcinoma of the bladder only after pathology re-review.
      Patients with small cell carcinoma of the bladder had a higher rate of advanced
      (pT3/4) tumor stage (84% vs 46%; P < 0.0001) and pN+ disease (37% vs 20%; P =
      0.001) compared with patients with urothelial carcinoma. When matched for stage
      and lymph node status, no significant difference in 5-year cancer-specific
      survival was observed between the two groups (27% vs 29%; P = 0.64). Among small
      cell carcinoma of the bladder patients, those receiving adjuvant chemotherapy had
      improved 5-year overall survival compared with patients who did not receive
      adjuvant chemotherapy (43% vs 20%; P = 0.03), and a trend toward superior cancer
      specific survival (40% vs 23%; P = 0.07). CONCLUSIONS: Small cell carcinoma of
      the bladder is often an unrecognized pathological entity, which is associated
      with a higher rate of locally advanced and N+ disease. However, although when
      matched for pathological features, survival outcomes appear similar to urothelial
      carcinoma. Small cell carcinoma of the bladder patients receiving adjuvant
      chemotherapy had improved overall survival and cancer-specific survival, and
      these results require further investigation.

PMID- 25761780
TI  - Topological proximity effect in a topological insulator hybrid.
AB  - It is well known that a topologically protected gapless state appears at an
      interface between a topological insulator and an ordinary insulator; however, the
      physics of the interface between a topological insulator and a metal has largely
      been left unexplored. Here we report a novel phenomenon termed topological
      proximity effect, which occurs between a metallic ultrathin film and a three
      dimensional topological insulator. We study one bilayer of bismuth metal grown on
      the three-dimensional topological insulator material TlBiSe2, and by using spin-
      and angle-resolved photoemission spectroscopy, we found evidence that the
      topological Dirac-cone state migrates from the surface of TlBiSe2 to the attached
      one-bilayer Bi. We show that such a migration of the topological state occurs as
      a result of strong spin-dependent hybridization of the wave functions at the
      interface, which is also supported by our first-principles calculations. This
      discovery points to a new route to manipulating the topological properties of
      materials. 

PMID- 25761781
TI  - The cholesterol biosynthesis enzyme oxidosqualene cyclase is a new target to
      impair tumour angiogenesis and metastasis dissemination.
AB  - Aberrant cholesterol homeostasis and biosynthesis has been observed in different
      tumour types. This paper investigates the role of the post-squalenic enzyme of
      cholesterol biosynthesis, oxidosqualene cyclase (OSC), in regulating tumour
      angiogenesis and metastasis dissemination in mouse models of cancer. We showed
      that Ro 48-8071, a selective inhibitor of OSC, reduced vascular density and
      increased pericyte coverage, with a consequent inhibition of tumour growth in a
      spontaneous mouse model of pancreatic tumour (RIP-Tag2) and two metastatic mouse
      models of human colon carcinoma (HCT116) and pancreatic adenocarcinoma (HPAF-II).
      Remarkably, the inhibition of OSC hampered metastasis formation in HCT116 and
      HPAF-II models. Ro 48-8071 induced tumour vessel normalization and enhanced the
      anti-tumoral and anti-metastatic effects of 5-fluorouracil (5-FU) in HCT116 mice.
      Ro 48-8071 exerted a strong anti-angiogenic activity by impairing endothelial
      cell adhesion and migration, and by blocking vessel formation in angiogenesis
      assays. OSC inhibition specifically interfered with the PI3K pathway. According
      to in vitro results, Ro 48-8071 specifically inhibited Akt phosphorylation in
      both cancer cells and tumour vasculature in all treated models. Thus, our results
      unveil a crucial role of OSC in the regulation of cancer progression and tumour
      angiogenesis, and indicate Ro 48-8071 as a potential novel anti-angiogenic and
      anti-metastatic drug. 

PMID- 25761782
TI  - Protein structural dynamics at the gas/water interface examined by hydrogen
      exchange mass spectrometry.
AB  - Gas/water interfaces (such as air bubbles or foam) are detrimental to the
      stability of proteins, often causing aggregation. This represents a potential
      problem for industrial processes, for example, the production and handling of
      protein drugs. Proteins possess surfactant-like properties, resulting in a high
      affinity for gas/water interfaces. The tendency of previously buried nonpolar
      residues to maximize contact with the gas phase can cause significant structural
      distortion. Most earlier studies in this area employed spectroscopic tools that
      could only provide limited information. Here we use hydrogen/deuterium exchange
      (HDX) mass spectrometry (MS) for probing the conformational dynamics of the model
      protein myoglobin (Mb) in the presence of N(2) bubbles. HDX/MS relies on the
      principle that unfolded and/or highly dynamic regions undergo faster deuteration
      than tightly folded segments. In bubble-free solution Mb displays EX2 behavior,
      reflecting the occurrence of short-lived excursions to partially unfolded
      conformers. A dramatically different behavior is seen in the presence of N(2)
      bubbles; EX2 dynamics still take place, but in addition the protein shows EX1
      behavior. The latter results from interconversion of the native state with
      conformers that are globally unfolded and long-lived. These unfolded species
      likely correspond to Mb that is adsorbed to the surface of gas bubbles. N(2)
      sparging also induces aggregation. To explain the observed behavior we propose a
      simple model, that is, "semi-unfolded" <-> "native" <-> "globally unfolded" ->
      "aggregated". This model quantitatively reproduces the experimentally observed
      kinetics. To the best of our knowledge, the current study marks the first
      exploration of surface denaturation phenomena by HDX/MS.

PMID- 25761784
TI  - Togetherness in another way: Internet as a tool for togetherness in everyday
      occupations among older adults.
AB  - OBJECTIVE: This article explores and describes how the Internet was experienced
      as a tool for togetherness in everyday occupations among older adults. METHODS:
      Discussions with 12 older adults, divided into three focus groups, generated data
      that were analysed using a grounded theory approach. Six women and six men
      between 67 and 79 years of age were purposively selected and recruited from a
      retirement organization in northern Sweden. RESULTS: Findings reflect how online
      contexts generated new possibilities for togetherness in everyday occupations and
      created a sense of belonging with others and to society at large. However,
      togetherness through the Internet was also associated with ambiguity and
      uncertainty among older adults. The Internet provided opportunities for
      togetherness that were somehow different from togetherness derived from face-to
      face contact, but it was also connected with a fear and a resistance.
      CONCLUSIONS: Findings from this research can extend our understanding of how
      online contexts have the possibility to promote togetherness in everyday
      occupations and what it means to be part of such a context among older adults. In
      light of these findings, the need is highlighted to consider the Internet as a
      tool for older adults to be socially engaged with the potential to reduce
      loneliness and isolation.

PMID- 25761783
TI  - A high-fat plus fructose diet produces a vascular prostanoid alterations in the
      rat.
AB  - In the rat, a high-fat (HF) plus fructose (F) diet produces cardiovascular and
      metabolic alterations that resemble human metabolic syndrome. Prostanoids (PR),
      cyclo-oxygenase-derived arachidonic acid metabolites, have vasoactive properties
      and mediate inflammation. The aim of this study was to analyse the effect of a
      HF+F diet on blood pressure (BP), metabolic parameters and mesenteric vascular
      bed PR production in male Sprague-Dawley rats. Four groups were studied over 9
      weeks (n = 6 each): control (C), standard diet (SD) and tap water to drink; F+SD
      and 10% w/v F solution to drink; HF 50% (w/w) bovine fat added to SD and tap
      water; and HFF, both treatments. PR were determined by HPLC. Blood pressure was
      elevated in all experimental groups. Triglyceridaemia, insulinaemia and HOMA-IR
      were increased in the F and HF groups. HF+F animals showed elevated glycaemia,
      insulinaemia, HOMA-IR and triglyceridaemia. F decreased the vasodilator
      prostanoids PGI2 and PGE2 in the mesenteric vascular bed. Body weight was not
      significantly altered. In HFF, production of PGE2 , PGF2 alpha and TXB2 was
      elevated. The increased BP in HF and HFF could be partly attributed to the
      imbalance in vascular PR production towards vasoconstrictors. On the other hand,
      this dietary modification could induce inflammation, which would explain the
      elevation of PGE2 . In the F group, hypertension could be related to decreased
      vasodilator PRs. The simultaneous administration of HF and F in the rat produces
      deleterious effects greater than observed when treatments are applied separately.

PMID- 25761785
TI  - Direct likelihood inference and sensitivity analysis for competing risks
      regression with missing causes of failure.
AB  - Competing risks arise in the analysis of failure times when there is a
      distinction between different causes of failure. In many studies, it is difficult
      to obtain complete cause of failure information for all individuals. Thus,
      several authors have proposed strategies for semi-parametric modeling of
      competing risks when some causes of failure are missing under the missing at
      random (MAR) assumption. As many authors have stressed, while semi-parametric
      models are convenient, fully-parametric regression modeling of the cause-specific
      hazards (CSH) and cumulative incidence functions (CIF) may be of interest for
      prediction and is likely to contribute towards a fuller understanding of the time
      dynamics of the competing risks mechanism. We propose a so-called "direct
      likelihood" approach for fitting fully-parametric regression models for these two
      functionals under MAR. The MAR assumption not being verifiable from the observed
      data, we propose an approach for performing sensitivity analyses to assess the
      robustness of inferences to departures from this assumption. The method relies on
      so-called "pattern-mixture models" from the missing data literature and was
      evaluated in a simulation study. This sensitivity analysis approach is applicable
      to various competing risks regression models (fully-parametric or semi
      parametric, for the CSH or the CIF). We illustrate the proposed methods with the
      analysis of a breast cancer clinical trial, including suggestions for ad hoc
      graphical goodness-of-fit assessments under MAR. 

PMID- 25761786
TI  - A Randomised trial to investigate the erosive effect of hot drinks.
AB  - Research on dental erosion has largely been undertaken at room temperature
      despite fruit juice drinks often being consumed at elevated temperatures in the
      United Kingdom, notably during periods of convalesce. The aim of the study was to
      evaluate the erosive potential of two fruit juices containing acidic non
      alcoholic drinks at elevated temperatures in situ on human enamel after 5, 10 and
      15 days. A commercially available conventional apple and blackcurrant fruit juice
      drink was compared to a blackcurrant juice drink modified to have low erosive
      potential, and mineral water consumed at approximately 59  degrees C. Twenty-one
      healthy volunteers aged 18 or over participated in a single-centre, single-blind
      (blinded to the investigator), three-treatment crossover study. Subjects were
      randomised to a treatment sequence using a Latin square design. Subjects wore
      upper removable appliances containing one human enamel specimen from 9 am to 5 pm
      for 15 days for each beverage. Measurements of enamel loss were recorded after 5,
      10 and 15 days by contact surface profilometry. The low erosive blackcurrant
      drink caused significantly less enamel loss (P < 0.05) than the commercially
      available conventional apple and blackcurrant fruit juice drink and was not
      statistically significantly different to mineral water at any of the time points
      in the study. Consuming the modified low erosive blackcurrant drink at an
      elevated temperature resulted in negligible enamel loss in situ, consistent with
      room temperature findings. 

PMID- 25761787
TI  - Evaluation of serum amyloid-A as mortality predictor in continuous ambulatory
      peritoneal dialysis patients.

PMID- 25761788
TI  - [Rola ukladu wazopresynergicznego w zespole metabolicznym].
AB  - Zespol metaboliczny (ZM) stanowi polaczenie zaburzen metabolicznych, bedacych
      czynnikami ryzyka chorob ukladu sercowo-naczyniowego. Powyzsza patologie, zgodnie
      z ostatnimi danymi epidemiologicznymi, mozna obecnie rozpoznac u co czwartego
      doroslego czlowieka. Patogeneza zespolu metabolicznego stanowi nadal przedmiot
      intensywnych badan. Wazopresyna (AVP), znana z regulacji cisnienia tetniczego,
      odgrywa takze istotna role w zmianie aktywnosci glikogenolizy watrobowej, jak
      rowniez w wydzielaniu insuliny i glukagonu oraz w osrodkowej regulacji
      przyjmowania pokarmu. W osoczu osob z ZM opisano wzrost stezenia kopeptyny (CPT;
      C-koncowego fragmentu prowazopresyny). Dlatego tez, wydaje sie, ze lepsze
      zrozumienie roli ukladu wazopresynergicznego w patogenezie zespolu metabolicznego
      byc moze pozwoli na rozwoj profilaktyki i nowych metod terapeutycznych.

PMID- 25761789
TI  - Metabolic risk in men with ischaemic heart disease   and their participation in
      ambulatory   comprehensive cardiac rehabilitation.
AB  - BACKGROUND: With a growing population of patients with ischaemic heart disease
      (IHD), the number of interventional cardiology and cardiac surgery procedures is
      also increasing. This is particularly the case for patients with multivessel
      coronary disease who are treated with percutaneous coronary interventions (PCI)
      and coronary artery bypass grafting (CABG). A considerable part of the IHD
      population are subjects with metabolic syndrome (MetS) who participate in
      comprehensive cardiac rehabilitation (CCR) programs as a part of secondary
      prevention of cardiovascular disease. AIM: To evaluate prospectively conventional
      risk factors within MetS, including uric acid (UA) level, in men with IHD after
      PCI or CABG who participated in ambulatory CCR. METHODS: The study included 90
      adult men (mean age 59.1 +/- 7.31 years) with IHD after PCI (n = 63, 70%) or CABG
      (n = 27, 30%) referred for ambulatory CCR on average 30-60 days after an acute
      coronary syndrome. All subjects were examined twice 2 months apart - at the
      referral for CCR and after completion of CCR. MetS was diagnosed based on the
      measurement of systolic and diastolic blood pressure, waist circumference (WC),
      and high-density lipoprotein cholesterol, triglyceride (TG), and fasting blood
      glucose levels. In all subjects, UA level was also measured and the waist-to-hip
      ratio (WHR) and body mass index (BMI) were calculated. Following clinical
      evaluation and exercise test, each patient underwent 24 interval training
      sessions on a cycle ergometer. The patients received drug therapy including beta
      blockers, angiotensin-converting enzyme inhibitors, statins, and acetylsalicylic
      acid. As a part of CCR, the patients also received education regarding healthy
      lifestyle changes including physical activity, healthy diet, stress coping
      techniques, effects of nicotine and alcohol, and effective methods to eliminate
      these habits. RESULTS: In most subjects, WC, BMI and WHR did not change
      significantly after the period of 2 months of CCR, and WC and BMI increased in
      the CABG subgroup (p = 0.00003 and p = 0.0178, respectively). Irrespective of the
      type of cardiac intervention, significant increases in exercise capacity and
      physical effort tolerance were observed after 2 months of CCR (p < 0.00001). TG
      level increased in all participants (p = 0.0514) and in the PCI subgroup (p =
      0.0489). Systolic blood pressure decreased in all participants (p = 0.0216) and
      in the PCI subgroup (p = 0.0043). Mean UA level also decreased in all patients
      regardless of the type of cardiac intervention. Overall, the proportion of
      patients with the diagnosis of MetS did not change significantly after 2 months
      of CCR (36% vs. 31%, p > 0.05). However, the rate of MetS decreased in the PCI
      subgroup (from 46% to 29%, p = 0.043) and increased in the CABG subgroup (from
      11% do 37%, p = 0.0562). CONCLUSIONS: The effect of participation in CCR on the
      metabolic risk in men with IHD varies depending on the type of earlier cardiac
      intervention. The metabolic risk decreased in patients treated with PCI, while it
      increased in those treated with CABG. In order to reduce the metabolic risk,
      particularly in CABG patients, a CCR program requires intensification of the
      patient support including educational activities regarding diet and weight
      reduction as well as individually prescribed physical activity.

PMID- 25761790
TI  - Platelet count and volume indices in patients with contrast-induced acute kidney
      injury and acute myocardial infarction treated invasively.
AB  - BACKGROUND: The aetiology of contrast-induced acute kidney injury (CI-AKI) is not
      well understood. We hypothesised that the pathophysiology of CI-AKI and impaired
      coronary reperfusion (IR), observed after invasive treatment of acute myocardial
      infarction (AMI), could be similar and might be related to platelet count (PC)
      and platelet volume indices (PVI). AIM: To evaluate the relation between PC, PVI,
      IR, and CI-AKI in patients with AMI treated invasively. METHODS: A single-centre
      study evaluated 607 consecutive AMI-patients treated invasively. Comparative
      analyses were performed between patients with CI-AKI and without CI-AKI for the
      total study population (CI-AKI, n = 156; 25.7% vs. nCI-AKI, n = 451; 74.3%), for
      patients with diabetes mellitus (CI-AKI-DM, n = 56; 9.2% vs. nCI-AKI-DM, n = 123;
      20.3%), and for patients with baseline kidney dysfunction (CI-AKI-BKD, n = 31;
      5.1% vs. nCI-AKI-BKD, n = 67; 11.0%). Subjects with IR, who developed CI-AKI,
      were compared to the remaining patients with respect to platelet parameters (CI
      AKI-IR, n = 47; 7.7% vs. controls, n = 560; 92.3%). For total population, as well
      as studied subgroups, multivariate logistic regression analyses were performed to
      reveal independent factors associated with CI-AKI. The results of the models were
      reported as odds ratios (OR) and 95% confidence intervals (95% CI). RESULTS: PC
      was higher in CI-AKI-DM-patients (224.8 +/- 62.8 * 10(9)/L vs. 197.9 +/- 63.3 *
      10(9)/L; p = 0.014) and in CI-AKI-BKD-patients (248.9 +/- 86.5 * 10(9)/L vs.
      202.5 +/- 59.3 * 10(9)/L; p = 0.004) than in appropriate controls. Within the
      studied groups, there were no differences between CI-AKI and nCI-AKI patients
      with respect to PVI. Comparing CI-AKI-IR-patients with controls, no differences
      in PC or PVI were found. IR was observed more often in CI-AKI-patients than in
      nCI-AKI-patients only among diabetics (48.2% vs. 27.6%; p = 0.008). Increase in
      admission PC was independently associated with CI-AKI in patients with diabetes
      (per one unit increase OR 1.006; CI 1.0-1.01; p = 0.04) as well as with baseline
      kidney dysfunction (per one unit increase OR 1.01; CI 1,0-1,02; p = 0.02).
      CONCLUSIONS: Any similarities in the pathophysiology of CI-AKI and IR were not
      reflected in platelet parameters. CI-AKI development was not related to PVI;
      however, higher PC was an independent risk factor for CI-AKI in patients with
      diabetes or baseline kidney dysfunction.

PMID- 25761791
TI  - Change in the clinical profile of patients referred for coronary artery bypass
      grafting from 2004 to 2008. Trends in a single-centre study.
AB  - BACKGROUND AND AIMS: The aim of this study is to describe the changes that
      occurred between 2004 and 2008 in the profile of patients referred for off-pump
      surgical treatment of coronary artery disease, by determining changes in their
      clinical characteristics, surgical procedures, and their results. METHODS AND
      RESULTS: This study is a retrospective evaluation of 2827 consecutive patients
      treated in the units of the 1st Chair of Cardiology of the Medical University of
      Warsaw from 2004 to 2008. We identified and retrieved 133 preoperative,
      intraoperative, and postoperative parameters. The statistical analysis was
      performed on measurable data in the analysed subgroups, but the relationship
      between immeasurable data was also examined. Significant declines in duration of
      hospitalisation, systolic and diastolic blood pressure on admission, left
      ventricular ejection fraction, stable coronary disease on admission, relationship
      between venous and arterial conduits used as graft, and in-hospital infections
      were observed. Meanwhile, the prevalence of arterial hypertension, of chronic
      pulmonary diseases, smoke, neurological dysfunction, heart rate on admission,
      diagnosis of two- and three-vessel disease and acute coronary syndrome/unstable
      angina, additive and logistic EuroScore, and average number of postoperative days
      in intensive care unit increased. More operations were performed as
      urgent/emergency cases, with higher numbers of grafts - which were more often
      arterial - per patient. An increase of length of the operation, blood loss and
      need for transfusion were observed as well as increased need for reoperation for
      bleeding. CONCLUSIONS: Patients referred for coronary artery surgery are becoming
      higher-risk patients with a greater number of comorbidities, and surgical
      techniques are becoming progressively more sophisticated.

PMID- 25761792
TI  - Differential expression of hyperpolarization-activated cyclic nucleotide-gated
      channel subunits during hippocampal development in the mouse.
AB  - BACKGROUND: Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels
      help control the rhythmic activation of pacemaker neurons during brain
      development. However, little is known about the timing and cell type specificity
      of the expression of HCN isoforms during development of the hippocampus. RESULTS:
      Here we examined the developmental expression of the brain-enriched HCN1, HCN2,
      and HCN4 isoforms of HCN channels in mouse hippocampus from embryonic to
      postnatal stages. All these isoforms were expressed abundantly in the hippocampus
      at embryonic day 14.5 and postnatal day 0. Each HCN channel isoform showed
      subfield-specific expression within the hippocampus from postnatal day 7, and
      only HCN4 was found in glial cells in the stratum lacunosum moleculare at this
      developmental stage. At postnatal days 21 and 56, all HCN isoforms were strongly
      expressed in the stratum lacunosum moleculare and the stratum pyramidale of the
      Cornu Ammonis (CA), as well as in the hilus of the dentate gyrus, but not in the
      subgranular zone. Furthermore, the immunolabeling for all these isoforms was
      colocalized with parvalbumin immunolabeling in interneurons of the CA field and
      in the dentate gyrus. CONCLUSIONS: Our mapping data showing the temporal and
      spatial changes in the expression of HCN channels suggest that HCN1, HCN2, and
      HCN4 subunits may have distinct physiological roles in the developing
      hippocampus.

PMID- 25761794
TI  - Akt-mediated regulation of antidepressant-sensitive serotonin transporter
      function, cell-surface expression and phosphorylation.
AB  - The serotonin [5-HT (5-hydroxytryptamine)] transporter (SERT) controls
      serotonergic neurotransmission in the brain by rapid clearance of 5-HT from the
      synaptic cleft into presynaptic neurons. SERTs are primary targets for
      antidepressants for therapeutic intervention of mood disorders. Our previous
      studies have identified the involvement of several signalling pathways and
      protein kinases in regulating SERT function, trafficking and phosphorylation.
      However, whether Akt/PKB (protein kinase) regulates SERT function is not known.
      In the present study, we made the novel observation that inhibition of Akt
      resulted in the down-regulation of SERT function through the regulation of SERT
      trafficking and phosphorylation. Akt inhibitor Akt X {10-(4'-[N
      diethylamino)butyl]-2-chlorophenoxazine} reduced the endogenously phosphorylated
      Akt and significantly decreased 5-HT uptake and 5-HT-uptake capacity.
      Furthermore, SERT activity is also reduced by siRNA down-regulation of total and
      phospho-Akt levels. The reduction in SERT activity is paralleled by lower levels
      of cell-surface SERT protein, reduced SERT exocytosis with no effect on SERT
      endocytosis and accumulation of SERT in intracellular endocytic compartments with
      the most prominent localization to late endosomes and lysosomes. Akt2 inhibitor
      was more effective than Akt1 inhibitor in inhibiting SERT activity. Inhibition of
      downstream Akt kinase GSK3alpha/beta (glycogen synthase kinase alpha/beta)
      stimulates SERT function. Akt inhibition leads to a decrease in SERT basal
      phosphorylation. Our results provide evidence that Akt regulates SERT function
      and cell-surface expression by regulating the intracellular SERT distribution and
      plasma membrane availability, which perhaps may be linked to SERT phosphorylation
      state. Thus any changes in the activation of Akt and/or GSK3alpha/beta could
      alter SERT-mediated 5-HT clearance and subsequently serotonergic
      neurotransmission. 

PMID- 25761793
TI  - Trends of non-union and prescriptions for non-steroidal anti-inflammatory drugs
      in the United States, 1993-2012.
AB  - BACKGROUND AND PURPOSE: Surgical care and pain management for patients with
      fractures have evolved over the years. We wanted to ascertain if there were any
      changes in the incidence of non-unions and, if so, whether the use of non
      steroidal anti-inflammatory drugs (NSAIDs), including COX-2 selective inhibitors,
      might have an effect. PATIENTS AND METHODS: We used the National Inpatient Sample
      (NIS) to estimate the annual number of patients hospitalized for surgical
      treatment of a non-union between 1993 and 2012, and calculated age-adjusted rates
      of non-union. We estimated the prevalence of prescriptions for NSAIDs from 1996
      through 2012 using the Medical Expenditure Panel Survey (MEPS). The interrupted
      time-series analysis was used to relate quarterly rates of non-union to changes
      in prescriptions for NSAIDs between 1996 and 2009. RESULTS: The annual estimate
      of non-unions in the USA declined 30% from 25,634 in 1993 to 17,815 in 2012 (p <
      0.001). Specifically, the age-adjusted rate of non-unions decreased by 44% from
      8.6 per 10(5) persons in 1996 to 4.8 per 10(5) persons in 2012 (p < 0.001).
      However, there was an 8% increase in the incidence rate of non-unions (p = 0.003)
      between 2000 and 2004, when certain COX-2 selective inhibitors were on the market
      and their prescriptions were prevalent at around 6% among those with fractures. A
      drop in non-union estimates from 22,321 in 2010 to 18,789 in 2011 (p = 0.04) also
      coincided with a marked decrease in prescriptions for NSAIDs in patients with
      fractures, from 22% to 14% (p = 0.02). INTERPRETATION: Non-unions in the USA
      declined substantially between 1993 and 2012, but this was interrupted by changes
      in prescriptions for NSAIDs, with sustained increases between 2000 and 2004
      followed by transient decreases in 2005 and 2011.

PMID- 25761796
TI  - Relationship between crystal structure and thermo-mechanical properties of
      kaolinite clay: beyond standard density functional theory.
AB  - The structural, mechanical and thermodynamic properties of 1 : 1 layered
      dioctahedral kaolinite clay, with ideal Al2Si2O5(OH)4 stoichiometry, were
      investigated using density functional theory corrected for dispersion
      interactions (DFT-D2). The bulk moduli of 56.2 and 56.0 GPa predicted at 298 K
      using the Vinet and Birch-Murnaghan equations of state, respectively, are in good
      agreement with the recent experimental value of 59.7 GPa reported for well
      crystallized samples. The isobaric heat capacity computed for uniaxial
      deformation of kaolinite along the stacking direction reproduces calorimetric
      data within 0.7-3.0% from room temperature up to its thermal stability limit. 

PMID- 25761795
TI  - Thrombocytosis of Liver Metastasis from Colorectal Cancer as Predictive Factor.
AB  - There is increasing evidence that thrombocytosis is associated with tumor
      invasion and metastasis formation. It was shown in several solid tumor types that
      thrombocytosis prognosticates cancer progression. The aim of this study was to
      evaluate preoperative thrombocytosis as a potential prognostic biomarker in
      isolated metastases, in patients with liver metastasis of colorectal cancer
      (mCRC). Clinicopathological data of 166 patients with mCRC who had surgical
      resection between 2001 and 2011 were collected retrospectively. All primary
      tumors have been already resected. The platelet count was evaluated based on the
      standard preoperative blood profile. The patients were followed-up on average for
      28 months. Overall survival (OS) of patients with thrombocytosis was
      significantly worse both in univariate (HR = 3.00, p = 0.03) and in multivariate
      analysis (HR = 4.68, p = 0.056) when adjusted for gender, age, tumor size and
      surgical margin. Thrombocytosis was also a good prognosticator of disease-free
      survival (DFS) with HR = 2.7, p = 0.018 and nearly significant in multivariate
      setting (HR = 2.26, p = 0.073). The platelet count is a valuable prognostic
      marker for the survival in patients with mCRC.

PMID- 25761798
TI  - Is there a threat to academic medicine? A forward look to 2048.

PMID- 25761799
TI  - NCEPOD: benchmarking and shaping practice in surgical care and beyond.

PMID- 25761801
TI  - Management of colonic polyps and the NHS Bowel Cancer Screening Programme.
AB  - This article describes the NHS Bowel Cancer Screening Programme and the
      management of large colonic polyps, many of which are diagnosed and managed
      successfully during bowel cancer screening, in addition to non-endoscopic
      management options. 

PMID- 25761797
TI  - Association between MTHFR C677T polymorphism and risk of acute lymphoblastic
      leukemia: a meta-analysis based on 51 case-control studies.
AB  - BACKGROUND: Studies and systematic reviews have reached inconsistent conclusions
      on the role of 5, 10-methylenetetrahydrofolate reductase (MTHFR) polymorphism
      C677T in acute lymphoblastic leukemia (ALL) risk. MATERIAL AND METHODS: The
      present meta-analysis comprising of 51 case-control studies, including 7892 cases
      and 14 280 controls was performed to reevaluate the association between MTHFR
      C677T polymorphism and ALL risk. RESULTS: Statistical differences were found in
      the dominant model (TT+CT vs. CC, odd ratio (OR)=0.89, 95% CI, 0.79-1.00, P=0.04)
      and the CT vs. CC (OR=0.89, 95% CI, 0.80-1.00, P=0.05), but not in the allele
      contrast model (T vs. C, OR=0.92, 95% CI, 0.84-1.01, P=0.08), additive model (TT
      vs. CC, OR=0.87, 95% CI, 0.73-1.05, P=0.15), or recessive model (TT vs. CT+CC,
      OR=0.94, 95% CI, 0.81-1.10, P=0.44) in overall populations. In the subgroup
      analyses stratified by age (children and adults) and ethnicity (Asian and
      Caucasian), no significant associations between MTHFR C677T polymorphism and ALL
      risk were observed. CONCLUSIONS: The current study found no sufficient evidence
      of a protective role of MTHFR C677T polymorphism in ALL susceptibility.

PMID- 25761802
TI  - Epidemiology and risk factors for Barrett's oesophagus.
AB  - The highest incidence and prevalence of Barrett's oesophagus is in western
      countries. Risk factors include smoking, obesity, gastro-oesophageal reflux
      disease and hiatus hernia, increasing age and use of oral bisphosphonates. This
      article discusses the significance of these findings. 

PMID- 25761803
TI  - Current management of fistula-in-ano.
AB  - Anal fistulae management is a balance of effective healing and the risk of
      incontinence from sphincter division. This review examines the heterogeneity in
      the literature of treatment options and the difficulties this presents for
      surgical training and decision making. 

PMID- 25761804
TI  - Power tool injuries to the hand and wrist.
AB  - Power tool injuries to the hand and wrist are complex injuries which can have a
      profound impact on the function of the patient. This article gives an overview of
      the principles, and provides a systematic approach, to the management and
      rehabilitation of the injured limb and patient required to minimize future
      disability. 

PMID- 25761805
TI  - Acute sarcoidosis: Lofgren's syndrome.
AB  - Sarcoidosis is a chronic multisystem granulomatous inflammatory disorder. It can
      present acutely which is known as Lofgren's syndrome. The diagnosis may be missed
      if clinicians are not aware of its classic presenting features and the
      appropriate diagnostic investigations. 

PMID- 25761806
TI  - Carbon monoxide poisoning: an ancient and frequent cause of accidental death.
AB  - Carbon monoxide poisoning is both an ancient and current cause of inadvertent
      (accidental) death and more recently has emerged as a cause of suicide worldwide.
      This article describes the pathophysiology and epidemiology of this most toxic
      and frequently occult poison. 

PMID- 25761807
TI  - 'On the Right Trach?' A review of the care received by patients who undergo
      tracheostomy.
AB  - An National Confidential Enquiry into Patient Outcome and Death (NCEPOD) study
      published in June 2014 reviewed the care of more than 2000 patients who had a new
      tracheostomy formed during an 11-week period in 2013 in the UK, two thirds of
      which were inserted at the bedside in a critical care unit. Many more patients in
      hospitals now have a tracheostomy, and this article summarizes the lessons from
      the report which are particularly important for secondary care clinicians. 

PMID- 25761808
TI  - Supporting the engagement of doctors in training in quality improvement and
      patient safety.
AB  - This article discusses how doctors in training and medical students' routine,
      formal and meaningful engagement in quality improvement initiatives is a vital
      component of establishing a 'culture of care'. 

PMID- 25761809
TI  - Franz Mesmer: pioneer in the treatment of functional disease or charlatan?

PMID- 25761810
TI  - Imperial college school of medicine surgical society annual international trauma
      conference.

PMID- 25761811
TI  - Spontaneous tumour lysis syndrome with follicular lymphoma.

PMID- 25761812
TI  - An unusual cause of a marked leukocytosis and an abnormal blood film.

PMID- 25761813
TI  - Could the growing number of physician associates affect the procedural competence
      of our trainees?

PMID- 25761814
TI  - Malignant hypertension in lgA nephropathy.

PMID- 25761815
TI  - Nitrous oxide use during general anaesthesia for general surgical cases.

PMID- 25761816
TI  - Overview of pancreatic resections: indications and procedures.

PMID- 25761817
TI  - Assessing the sense of smell.

PMID- 25761818
TI  - Hyposmia.

PMID- 25761819
TI  - How to choose a suture.

PMID- 25761820
TI  - Histologic comparison between the internal mammary artery and the deep inferior
      epigastric artery and clinical implications for microsurgical breast
      reconstruction.
AB  - BACKGROUND: The internal mammary artery (IMA) is one of the most popular
      recipients for microsurgical breast reconstruction. However, it is often
      separated into sleeve-like layers when it is handled. This study tried to explain
      this unique behaviour of the IMA through histologic observation. METHODS: Nine
      pairs of IMAs and DIEAs were harvested and subject for haematoxylin-eosin and
      Verhoeff's elastic staining. Thickness of the tunica media and the number of
      elastic lamellae were compared. Samples of the IMA, the DIEA, and the
      thoracodorsal artery from another patient were observed through the transmission
      electron microscope to further show the structural differences. RESULTS: The most
      notable difference was presence of multiple elastic lamellae in tunica media in
      the IMAs, which was barely present in the DIEAs. The mean number of elastic
      lamellae was 9.2 in the IMA group and 1.0 in the DIEA group (p < 10(-9)). A
      transmission electron microscope showed that the tunica media of the DIEA and the
      TDA was densely packed with smooth muscle cells, while the muscle cells
      distributed sparsely in the IMA. CONCLUSIONS: The IMA is an elastic artery which
      is characterised by multiple layers of elastic lamellae while relatively lacking
      in smooth muscle cells. The wall of the IMA is easily dissected between the
      tunica media and the adventitia, or at the outer 1/3 of the tunica media. The
      inner structure is easily torn if microsutures do not engage the tunica
      adventitia.

PMID- 25761821
TI  - Persian Diabetes Self-Management Education (PDSME) program: evaluation of
      effectiveness in Iran.
AB  - Despite increasing rate of diabetes, no standard self-management education
      protocol has been developed in Iran. We designed Persian Diabetes Self-Management
      Education (PDSME) program using intervention mapping. Effectiveness of program
      was assessed in newly diagnosed people with type 2 diabetes and those who had
      received little self-management education. Individuals aged 18 and older (n =
      350) were recruited in this prospective controlled trial during 2009-2011 in
      Tehran, Iran. Patients were excluded if they were pregnant, were housebound or
      had reduced cognitive ability. Participants were randomly allocated in
      intervention and control groups. PDSME patients attended eight workshops over 4
      week period following two follow-up sessions. Validated questionnaires assessed
      cognitive outcomes at baseline, 2 and 8 weeks. HbA1c was assessed before and 18
      21 months after intervention in both groups. The CONSORT statement was adhered to
      where possible. A total of 280 individuals (80%) attended the program. By 18-21
      months, the PDSME group showed significant improvements in mean HbA1c (-1.1
      versus +0.2%, p =0.008, repeated measure ANOVA (RMA)). Diabetes knowledge
      improved more in PDSME patients treated with oral antidiabetic agents than in
      those receiving usual care over time (RMA, F = 67.08, p < 0.001). Statistically
      significant improvements were seen in PDSME patients for self-care behaviors,
      health beliefs, attitudes toward diabetes, stigma, self-efficacy and patient
      satisfaction. PDSME program was effective in improving self-management cognitive
      and clinical outcomes. Results support use of intervention mapping for planning
      effective interventions. Given the large number of people with diabetes and lack
      of affordable diabetes education, PDSME deserves consideration for
      implementation. 

PMID- 25761822
TI  - Origin of MLH1, MSH2, MSH6 and PMS2 mutations can help inform long-term care
      strategies for patients with colorectal and endometrial cancer.

PMID- 25761824
TI  - US health reform law will cost less than projected, says budget office.

PMID- 25761823
TI  - PCR for enteric pathogens in high-prevalence settings. What does a positive
      signal tell us?
AB  - BACKGROUND: Molecular methods, in particular PCR, are increasingly used for the
      diagnosis of enteric pathogens in stool samples. In high-endemicity settings,
      however, asymptomatic carriage or residual DNA from previous infections will
      hamper the interpretation of positive test results. We assessed the quantitative
      dimension of this problem in schoolchildren in the rural highlands of Madagascar.
      METHODS: Stool samples were collected from 410 apparently healthy Madagascan
      schoolchildren and analysed by multiplex real-time PCR for enteroinvasive
      bacteria (Salmonella spp., Shigella spp./enteroinvasive Escherichia coli (EIEC),
      Campylobacter jejuni, Yersinia spp.), enteric protozoa (Entamoebea histolytica,
      Giardia duodenalis, Cryptosporidium spp., Cyclospora spp.), and helminths
      (Ascaris lumbricoides, Ancylostoma spp., Necator americanus, Strongyloides
      stercoralis). Symptoms of gastrointestinal disease were assessed. RESULTS: Among
      the 410 samples, we detected Giardia duodenalis in 195, Campylobacter jejuni in
      91, Ascaris lumbricoides in 72, Cyclospora cayetanenesis in 68, Shigella
      spp./EIEC in 56, and Strongyloides stercoralis and Cryptosporum spp. in 1 case
      each. Salmonella spp., Yersinia spp. and hookworms were not observed. Relative
      risk assessment suggested few and incoherent associations with pathogen
      detections, indicating asymptomatic carriage or DNA residuals. Only 26.1% of the
      schoolchildren were tested negative for all analysed pathogens. CONCLUSIONS: The
      very high risk of detecting traces of asymptomatic carriage or residual DNA from
      previous infections limits the value of highly sensitive PCR for the causal
      attribution of detected enteric pathogens from stool samples to an infectious
      gastrointestinal disease in the high-endemicity setting. Evaluated standards for
      the interpretation of such results are needed both for the diagnostic routine and
      for epidemiological assessments.

PMID- 25761825
TI  - Utilizing the Cross-Reactivity of MIPs.
AB  - The crossreactivity of molecularly imprinted polymers (MIPs) and its practical
      implications are discussed. Screening of MIP libraries is presented as a
      fasttrack route to discovery of resins selective towards new targets, exploiting
      the fact that MIPs imprinted with one type of template molecule also show
      recognition to related and sometimes also to apparently unrelated molecules.
      Several examples from our own and others' studies are presented that illustrate
      this crossreactivity and the pattern of recognition is discussed for selected
      examples.

PMID- 25761826
TI  - Primary Gastric Hodgkin's Lymphoma: An Extremely Rare Entity and A Diagnostic
      Challenge.

PMID- 25761827
TI  - A Br-substituted phenanthroimidazole derivative with aggregation induced emission
      from intermolecular halogen-hydrogen interactions.
AB  - A unique aggregation induced emission (AIE) active emitter based on a Br
      substituted phenanthroimidazole derivative was reported. The yellowish green
      emission with high quantum yield and a large Stokes shift (~150 nm) in the
      aggregated state is proposed to be obtained from weak interactions especially C
      H...Br interactions.

PMID- 25761828
TI  - Multi-task feature selection via supervised canonical graph matching for
      diagnosis of autism spectrum disorder.
AB  - In this paper, we propose a novel framework for ASD diagnosis using structural
      magnetic resonance imaging (MRI). Our method deals explicitly with the
      distributional differences of gray matter (GM) and white matter (WM) features
      extracted from MR images. We project linearly the GM and WM features onto a
      canonical space where their correlations are mutually maximized. In this
      canonical space, features that are highly correlated with the class labels are
      selected for ASD diagnosis. In addition, graph matching is employed to preserve
      the geometrical relationships between samples when projected onto the canonical
      space. Our evaluations based on a public ASD dataset show that the proposed
      method outperforms all competing methods on all clinically important measures in
      differentiating ASD patients from healthy individuals. 

PMID- 25761830
TI  - Breast cancer: a new imaging approach as an addition to existing guidelines.

PMID- 25761831
TI  - Improving operating efficiency with emphasis on prosthetic surgery.

PMID- 25761832
TI  - Surgical management of hypogonadic patients with hypotrophic testicles and small
      penis: a novel, combined technique with an infrapubic approach.

PMID- 25761834
TI  - Combined tests of prostate specific antigen and testosterone will improve
      diagnosis and monitoring the progression of prostate cancer.
AB  - Prostate-specific antigen (PSA) testing has been widely used to screen men for
      prostate cancer (PCa) and to monitor PCa progression. However, more studies have
      shown that around 15% of men with low or normal PSA levels have PCa. In this
      study, we aimed to investigate the relationship of androgen and PSA levels and to
      better understand the reason that some PCa patients have low serum PSA values.
      The in vitro data demonstrated that cultured LNCaP cells ceased to produce PSA
      after androgen withdrawal and resumed PSA production after androgen was re-added.
      The in vivo experiment results showed that 48% of PCa xenografts carrying mice
      have serum PSA level lower than 4 ng ml-1 . The serum PSA levels increased
      significantly with rises in testosterone (T) levels 1 week after T pellet
      implantation. These data indicated that the androgen is a key factor controlling
      the production of PSA. Low serum PSA levels in mice with PCa xenografts are
      associated with low serum T levels. Raising serum T levels in tumor caring mice
      will also significantly increase serum PSA level. This may have clinical
      implications when screening PSA in men, who have occult PCa. 

PMID- 25761835
TI  - The feasibility and experience of using seminal vesiculoscopy in the diagnosis of
      primary seminal vesicle tumors.

PMID- 25761833
TI  - Effects of long-term androgen replacement therapy on the physical and mental
      statuses of aging males with late-onset hypogonadism: a multicenter randomized
      controlled trial in Japan (EARTH Study).
AB  - Androgen replacement therapy (ART) efficacy on late-onset hypogonadism (LOH) has
      been widely investigated in Western countries; however, it remains controversial
      whether ART can improve health and prolong active lifestyles. We prospectively
      assessed long-term ART effects on the physical and mental statuses of aging men
      with LOH in Japan. The primary endpoint was health-related quality of life
      assessed by questionnaires. Secondary endpoints included glycemic control, lipid
      parameters, blood pressure, waist circumference, body composition, muscular
      strength, International Prostate Symptom Scores (IPSS), International Index of
      Erectile Function-5 (IIEF-5) scores, and serum prostate-specific antigen levels.
      Of the 1637 eligible volunteers, 334 patients > 40 years with LOH were randomly
      assigned to either the ART (n = 169) or control groups (n = 165). Fifty-two weeks
      after the initial treatment, ART significantly affected the role physical
      subdomain of the short form-36 health survey (SF-36) scale (P = 0.0318). ART was
      also associated with significant decreases in waist circumstance (P = 0.002) and
      serum triglyceride (TG) (P = 0.013) and with significant increases in whole-body
      and leg muscle mass volumes (P = 0.071 and 0.0108, respectively), serum
      hemoglobin (P < 0.001), IPSS voiding subscore (P = 0.0418), and the second
      question on IIEF-5 (P = 0.0049). There was no significant difference between the
      groups in terms of severe adverse events. In conclusion, in patients with LOH,
      long-term ART exerted beneficial effects on Role Physical subdomain of the SF-36
      scale, serum TG, waist circumstance, muscle mass volume, voiding subscore of
      IPSS, and the second question of IIEF-5. We hope our study will contribute to the
      future development of this area. 

PMID- 25761836
TI  - Implicit attitudes towards smoking predict long-term relapse in abstinent
      smokers.
AB  - RATIONALE: It has previously been argued that implicit attitudes toward substance
      related cues drive addictive behavior. Nevertheless, it remains an open question
      whether behavioral markers of implicit attitude activation can be used to predict
      long-term relapse. OBJECTIVES: The main objective of this study was to examine
      the relationship between implicit attitudes toward smoking-related cues and long
      term relapse in abstaining smokers. METHODS: Implicit attitudes toward smoking
      related cues were assessed by means of the Implicit Association Test (IAT) and
      the evaluative priming task (EPT). Both measures were completed by a group of
      smokers who volunteered to quit smoking (patient group) and a group of nonsmokers
      (control group). Participants in the patient group completed these measures
      twice: once prior to smoking cessation and once after smoking cessation. Relapse
      was assessed by means of short telephone survey, 6 months after completion of the
      second test session. RESULTS: EPT scores obtained prior to smoking cessation were
      related to long-term relapse and correlated with self-reported nicotine
      dependence as well as daily cigarette consumption. In contrast, none of the
      behavioral outcome measures were found to correlate with the IAT scores.
      CONCLUSIONS: These findings corroborate the idea that implicit attitudes toward
      substance-related cues are critically involved in long-term relapse. A potential
      explanation for the divergent findings obtained with the IAT and EPT is provided.

PMID- 25761837
TI  - A double-blind, placebo-controlled study evaluating the effects of caffeine and L
      theanine both alone and in combination on cerebral blood flow, cognition and
      mood.
AB  - RATIONALE: Evidence suggests interactive effects of the tea components caffeine
      and L-theanine on behaviour, yet no data exists exploring the impact of the two
      on cerebral blood flow (CBF). OBJECTIVES: The current placebo-controlled, double
      blind, counterbalanced, crossover study examined the effects of caffeine and L
      theanine on CBF and extended previous cognitive and mood findings by using lower
      doses than previous studies of a similar methodology, which more closely reflect
      the ratios present in tea. METHODS: Twelve habitual consumers and 12 non-habitual
      consumers of caffeine each received 75 mg caffeine, 50 mg L-theanine, 75 mg
      caffeine plus 50 mg L-theanine, and placebo in a counterbalanced order across
      four separate visits. CBF was measured via near-infrared spectroscopy with
      cognition and mood assessed at baseline and 30 min post-dose. Salivary caffeine
      and peripheral haemodynamics were co-monitored. RESULTS: Caffeine reduced
      oxygenated haemoglobin (oxy-Hb), increased deoxygenated haemoglobin (deoxy-Hb),
      improved performance on attention tasks and increased overall mood ratings.
      Increases in deoxy-Hb following caffeine were more pronounced in non-consumers.
      Some evidence for increased deoxy-Hb remained when caffeine was combined with L
      theanine, but this effect was attenuated and the effects of caffeine on oxy-Hb,
      cognition and mood were eradicated. CONCLUSIONS: Combining L-theanine with
      caffeine, at levels and ratios equivalent to one to two cups of tea, eliminated
      the vasoconstrictive effect and behavioural effects of caffeine. This supports
      previous findings of an interaction between these substances, despite a lack of
      effects of L-theanine in isolation. However, at the levels tested here, this did
      not lead to a positive impact on behaviour.

PMID- 25761838
TI  - Exploring the role of drug-metabolising enzymes in antidepressant side effects.
AB  - RATIONALE: Cytochrome P450 enzymes are important in the metabolism of
      antidepressants. The highly polymorphic nature of these enzymes has been linked
      to variability in antidepressant metabolism rates, leading to hope regarding the
      use of P450 genotyping to guide treatment. However, evidence that P450 genotypic
      differences underlie the variation in treatment outcomes is inconclusive.
      OBJECTIVES: We explored the links between both P450 genotype and serum
      concentrations of antidepressant with antidepressant side effects, using data
      from the Genome-Based Therapeutic Drugs for Depression Project (GENDEP), which is
      a large (n = 868), pharmacogenetic study of depressed individuals treated with
      escitalopram or nortriptyline. METHODS: Patients were genotyped for the enzymes
      CYP2C19 and CYP2D6, and serum concentrations of both antidepressant and primary
      metabolite were measured after 8 weeks of treatment. Side effects were assessed
      weekly. We investigated associations between P450 genotypes, serum concentrations
      of antidepressants and side effects, as well as the relationship between P450
      genotype and study discontinuation. RESULTS: P450 genotype did not predict total
      side effect burden (nortriptyline: n = 251, p = 0.5638, beta = -0.133, standard
      error (SE) = 0.229; escitalopram: n = 340, p = 0.9627, beta = -0.004, SE =
      0.085), study discontinuation (nortriptyline n = 284, hazard ratio (HR) = 1.300,
      p = 0.174; escitalopram n = 376, HR = 0.870, p = 0.118) or specific side effects.
      Serum concentrations of antidepressant were only related to a minority of the
      specific side effects measured: dry mouth, dizziness and diarrhoea. CONCLUSIONS:
      In this sample where antidepressant dosage is titrated using clinical judgement,
      P450 genotypes do not explain differences between patients in side effects with
      antidepressants. Serum drug concentrations appear to only explain variability in
      the occurrence of a minority of specific side effects.

PMID- 25761839
TI  - WAY 267,464, a non-peptide oxytocin receptor agonist, impairs social recognition
      memory in rats through a vasopressin 1A receptor antagonist action.
AB  - RATIONALE: Recent in vitro studies suggest that the oxytocin receptor (OTR)
      agonist WAY 267,464 has vasopressin 1A receptor (V1AR) antagonist effects. This
      might limit its therapeutic potential due to the positive involvement of the V1AR
      in social behavior. OBJECTIVES: The objective of this study was to assess
      functional V1AR antagonist-like effects of WAY 267,464 in vivo using a test of
      social recognition memory. METHODS: Adult experimental rats were tested for their
      recognition of a juvenile conspecific rat that they had briefly met 30 or 120 min
      previously. The modulatory effects of vasopressin (AVP), the selective V1AR
      antagonist SR49059, and WAY 267,464 were examined together with those of the
      selective OTR antagonist Compound 25 (C25). Drugs were administered immediately
      after the first meeting. RESULTS: Control rats showed recognition of juveniles at
      a 30 min, but not a 120 min retention interval. AVP (0.005, but not 0.001 mg/kg
      intraperitoneal (i.p.)) improved memory such that recognition was evident after
      120 min. This was prevented by pretreatment with SR49059 (1 mg/kg) and WAY
      267,464 (10, 30, and 100 mg/kg). Given alone, SR49059 (1 mg/kg) and WAY 267,464
      (30 and 100 mg/kg) impaired memory at a 30 min retention interval. The impairment
      with WAY 267,464 was not prevented by C25 (5 mg/kg), suggesting V1AR rather than
      OTR mediation of the effect. Given alone, C25 also impaired memory. CONCLUSIONS:
      These results highlight a tonic role for endogenous AVP (and oxytocin) in social
      recognition memory and indicate that WAY 267,464 functions in vivo as a V1AR
      antagonist to prevent the memory-enhancing effects of AVP.

PMID- 25761841
TI  - Examination of the metabolite hydroxybupropion in the reinforcing and aversive
      stimulus effects of nicotine in rats.
AB  - BACKGROUND: Preclinical studies with bupropion in rodent models of nicotine
      dependence have generated equivocal findings with regard to translating the
      clinical efficacy of the antidepressant as a smoking cessation agent. OBJECTIVE:
      Given that rats are poor metabolizers of bupropion, the present experiments
      examined (2S,3S)-hydroxybupropion, the major active metabolite, on the positive
      reinforcing and aversive stimulus properties of nicotine in rats. METHODS: In
      male hooded Lister rats, (2S,3S)-hydroxybupropion (1.0-10.0 mg/kg IP) was tested
      on intravenous nicotine (0.03 mg/kg/inf) self-administration behaviour for three
      sessions (n = 8), and in another experiment, the same doses of (2S,3S)
      hydroxybupropion were tested in a conditioned taste aversion procedure to assess
      the aversive stimulus properties of nicotine, a function implicated in the
      regulation of nicotine intake. RESULTS: (2S,3S)-hydroxybupropion attenuated
      nicotine intake in a manner similar to that produced by mecamylamine pretreatment
      (1.0 mg/kg SC). This effect on nicotine-taking was specific since these doses had
      no effect on responding maintained by sucrose presented orally (200 MUl of 5 %
      w/v). (2S,3S)-hydroxybupropion (1, 3 and 10 mg/kg IP) pretreatment failed to
      modify the aversive effects produced by a small dose of nicotine (0.1 mg/kg SC).
      CONCLUSIONS: These results demonstrate this metabolite to specifically modify the
      positive reinforcing effects of nicotine without affecting its aversive
      motivational effects. We propose that the clinical efficacy of bupropion may be
      due to a combination of effects produced by bupropion and/or its active
      metabolite (2S,3S)-hydroxybupropion involving the inhibition of reuptake of
      dopamine and noradrenaline in reward centres of the brain and the noncompetitive
      antagonism of neuronal nicotinic receptors.

PMID- 25761840
TI  - Noradrenergic modulation of risk/reward decision making.
AB  - RATIONALE: Catecholamine transmission modulates numerous cognitive and reward
      related processes that can subserve more complex functions such as cost/benefit
      decision making. Dopamine has been shown to play an integral role in decisions
      involving reward uncertainty, yet there is a paucity of research investigating
      the contributions of noradrenaline (NA) transmission to these functions.
      OBJECTIVES: The present study was designed to elucidate the contribution of NA to
      risk/reward decision making in rats, assessed with a probabilistic discounting
      task. METHODS: We examined the effects of reducing noradrenergic transmission
      with the alpha2 agonist clonidine (10-100 MUg/kg), and increasing activity at
      alpha2A receptor sites with the agonist guanfacine (0.1-1 mg/kg), the alpha2
      antagonist yohimbine (1-3 mg/kg), and the noradrenaline transporter (NET)
      inhibitor atomoxetine (0.3-3 mg/kg) on probabilistic discounting. Rats chose
      between a small/certain reward and a larger/risky reward, wherein the probability
      of obtaining the larger reward either decreased (100-12.5 %) or increased (12.5
      100 %) over a session. RESULTS: In well-trained rats, clonidine reduced risky
      choice by decreasing reward sensitivity, whereas guanfacine did not affect choice
      behavior. Yohimbine impaired adjustments in decision biases as reward probability
      changed within a session by altering negative feedback sensitivity. In a subset
      of rats that displayed prominent discounting of probabilistic rewards, the lowest
      dose of atomoxetine increased preference for the large/risky reward when this
      option had greater long-term utility. CONCLUSIONS: These data highlight an
      important and previously uncharacterized role for noradrenergic transmission in
      mediating different aspects of risk/reward decision making and mediating reward
      and negative feedback sensitivity.

PMID- 25761842
TI  - Differential involvement of anxiety and novelty preference levels on oral ethanol
      consumption in rats.
AB  - RATIONALE: Drug addiction is defined as a recurring cycle of intoxication,
      abstinence and relapse. The behavioural trait of novelty seeking is frequently
      observed in alcohol abusers. Moreover, converging evidence indicates that anxious
      individuals are also predisposed to alcohol abuse. OBJECTIVES: We have analyzed
      the respective implication of those two behavioural factors on vulnerability to
      ethanol intake on rats in situations designed to reflect drug intoxication and
      relapse phases in humans. METHODS: In a general population of Wistar rats,
      animals were tested in both the light/dark box and the novelty preference tests.
      Ethanol consumption was measured in a two-bottle free-choice procedure across
      three successive procedures. Animals were first exposed to increasing
      concentrations of ethanol (2, 4, 6, 8, 10, 12 % for 8 days at each
      concentration). Then, the concentration of the solution was diminished from 12 to
      6 %. Finally, all rats were re-exposed to 6 % ethanol after 12 days of ethanol
      deprivation. RESULTS: Novelty preference predicted the amount of ethanol consumed
      across all phases. In contrast, anxiety was associated with a quicker recovery of
      ethanol consumption after the concentration drop and a greater increase in
      ethanol consumption after deprivation. CONCLUSIONS: Novelty seeking and anxiety
      are both but differentially implicated in predisposition to ethanol abuse.
      Whereas novelty seeking is related to the amount of ethanol consumed, anxiety is
      associated to higher ethanol consumption when ethanol concentration is decreased
      or after ethanol deprivation.

PMID- 25761844
TI  - Organisational structure of liver transplantation in the UK.
AB  - AIM: This review aims to outline the delivery of liver transplant services in the
      UK. BACKGROUND: Liver transplantation in the UK is based on seven designated
      transplant units serving a population of just over 60 million people. Nearly 900
      liver transplants were done in 2013/2014. PROCESS: Potential deceased donors are
      identified and referred to centrally employed specialist nurses for obtaining
      family consent and for donor characterisation. Organs are retrieved by a National
      Organ Retrieval Service, based on seven abdominal and six cardiothoracic
      retrieval teams providing a 24/7 service which has shown to be capable of
      retrieving organs from up to ten donors a day. Donated organs are allocated first
      nationally to those who qualify for super-urgent listing. The next priority is
      for splitting livers, and if there is no suitable recipient or the liver is not
      suitable for splitting, then livers are offered first to the local centre; each
      centre has a designated donor zone, adjusted annually to ensure equity between
      the number of patients listed and the number of donors. The allocation scheme is
      being reviewed, and national schemes based on need, utility and benefit are being
      assessed. GOVERNANCE: Outcomes are monitored by National Health Service Blood and
      Transplant (NHSBT), and if there is a possibility of adverse deviation, then
      further inquiries are made. Outcomes, both from listing and from transplantation,
      are published by the centre on the NHSBT website ( www.odt.nhs.uk ). NHSBT works
      closely with stakeholders primarily through the advisory groups with clinicians,
      patients, lay members and professional societies and aims to provide openness and
      transparency. CONCLUSIONS: The system for organ donation and delivery of liver
      transplant in the UK has developed and is now providing an effective and
      efficient service, but there remains room for improvement.

PMID- 25761845
TI  - Medical cannabis vs. synthetic cannabinoids: What does the future hold?
AB  - The medical use of cannabis has an intricate therapeutic history that finds its
      roots in ancient China (~2700 BC). The main psychoactive component of cannabis,
      Delta(9) -tetrahydrocannabinol (Delta(9) -THC), was discovered in 1964. This was
      a significant breakthrough, as it allowed the generation of synthetic analogs of
      Delta(9) -THC, the discovery of cannabinoid receptors, and the generation of
      synthetic small molecules. Despite this, today there is still a paucity of drugs
      that target the cannabinoid system. 

PMID- 25761843
TI  - The mitochondria in diabetic heart failure: from pathogenesis to therapeutic
      promise.
AB  - SIGNIFICANCE: Diabetes is an important risk factor for the development of heart
      failure (HF). Given the increasing prevalence of diabetes in the population,
      strategies are needed to reduce the burden of HF in these patients. RECENT
      ADVANCES: Diabetes is associated with several pathologic findings in the heart
      including dysregulated metabolism, lipid accumulation, oxidative stress, and
      inflammation. Emerging evidence suggests that mitochondrial dysfunction may be a
      central mediator of these pathologic responses. The development of therapeutic
      approaches targeting mitochondrial biology holds promise for the management of HF
      in diabetic patients. CRITICAL ISSUES: Despite significant data implicating
      mitochondrial pathology in diabetic cardiomyopathy, the optimal pharmacologic
      approach to improve mitochondrial function remains undefined. FUTURE DIRECTIONS:
      Detailed mechanistic studies coupled with more robust clinical phenotyping will
      be necessary to develop novel approaches to improve cardiac function in diabetes.
      Moreover, understanding the interplay between diabetes and other cardiac
      stressors (hypertension, ischemia, and valvular disease) will be of the utmost
      importance for clinical translation of scientific discoveries made in this field.

PMID- 25761846
TI  - Has hypofractionated radiotherapy become the standard of care in pediatric DIPG?

PMID- 25761847
TI  - Competing Forces in the Self-Assembly of Coupled ZnO Nanopyramids.
AB  - Self-assembly (SA) of nanostructures has recently gained increasing interest. A
      clear understanding of the process is not straightforward since SA of
      nanoparticles is a complex multiscale phenomenon including different driving
      forces. Here, we study the SA between aluminum doped ZnO nanopyramids into
      couples by combining inorganic chemistry and advanced electron microscopy
      techniques with atomistic simulations. Our results show that the SA of the
      coupled nanopyramids is controlled first by morphology, as coupling only occurs
      in the case of pyramids with well-developed facets of the basal planes. The
      combination of electron microscopy and atomistic modeling reveals that the
      coupling is further driven by strong ligand-ligand interaction between the bases
      of the pyramids as dominant force, while screening effects due to Al doping or
      solvent as well as core-core interaction are only minor contributions. Our
      combined approach provides a deeper understanding of the complex interplay
      between the interactions at work in the coupled SA of ZnO nanopyramids. 

PMID- 25761848
TI  - Value-Based Health Care.

PMID- 25761849
TI  - Costs Versus Benefits of Routine Histopathological Examination in Total Ankle
      Replacement.
AB  - BACKGROUND: Routine histopathological examination has previously been scrutinized
      as a source of extraneous cost in orthopedic foot and ankle care. As an
      increasingly prevalent joint replacement operation, total ankle replacement poses
      a notable cost to the health care market in an era of cost containment. The
      purpose of this study was to compare the costs and benefits of routine
      histopathological examination of specimens removed during total ankle
      replacement. We hypothesized that a new diagnosis would rarely be found and such
      examination would seldom alter patient care. METHODS: A retrospective review was
      conducted of all total ankle replacement operations between 2006 and July 2014 at
      the investigators' institution. Medical records for 90 patients, undergoing a
      total of 95 total ankle replacement operations, were reviewed to determine the
      clinical and pathological diagnoses for each operation and, subsequently, the
      rates of discrepancy and discordance. Professional charges were determined using
      estimated reimbursement rates for the Current Procedural Terminology (CPT) codes
      billed: 88304 (level III microscopic examination), 88305 (level IV microscopic
      examination), and 88311 (decalcification). RESULTS: Degenerative joint disease
      was diagnosed by the pathologist in 93.7% of cases (89/95), pseudogout in 4.2%
      (4/95), and rheumatoid arthritis in 2.1% (2/95). The 4 diagnoses of pseudogout
      were the only cases of new diagnoses based on pathological review. A total of
      $16,536.81 was spent for examination of all specimens, for an estimated $4,134.20
      spent per discrepant diagnosis. Patient care was unaffected by pathological
      examination. CONCLUSION: A new diagnosis was rarely found by histopathological
      examination, and patient care remained unaltered in all cases. The costs of
      routine histopathological examination of tissue specimens removed during total
      ankle replacement, therefore, outweigh clinical benefits, and such examination
      should be left to the discretion of the operating surgeon. LEVEL OF EVIDENCE:
      Level IV, retrospective case series.

PMID- 25761850
TI  - Ankle Arthroscopy Simulation Improves Basic Skills, Anatomic Recognition, and
      Proficiency During Diagnostic Examination of Residents in Training.
AB  - BACKGROUND: The purpose of this study was to determine whether low-fidelity
      arthroscopic simulation training improves basic ankle arthroscopy performance and
      efficiency among orthopedic trainees. METHODS: Twenty-nine orthopedic surgery
      trainees with varying levels of experience in ankle arthroscopy were randomized
      into either simulation or standard practice groups. At baseline testing, all
      participants performed simulator-based testing and a cadaveric diagnostic ankle
      arthroscopy with video recording. The simulation group subsequently received 4
      one-on-one, 15-minute simulation training sessions over a 4-month period, while
      the standard practice group received no additional simulation training or
      exposure. After intervention, both groups were reevaluated with simulator testing
      and a second recorded cadaveric diagnostic ankle arthroscopy. Two blinded,
      independent experts evaluated each randomized arthroscopic performance using the
      15-point checklist, Arthroscopic Surgery Skill Evaluation Tool (ASSET), and total
      elapsed time, and all outcome measures were compared within and between groups.
      RESULTS: Baseline arthroscopic experience, simulator task performance measures,
      and ASSET scores were equivalent between the simulation and standard practice
      groups. After completion of training, the simulation group outscored the control
      group in total ASSET score (34.9 vs 19.6; P < .001) and checklist score (14.5 vs
      8.4; P < .001) and achieved nearly expert ASSET Safety scores (4.7 vs 2.9; P <
      .001) on the simulator model. Cadaver testing also demonstrated significant
      improvements in total ASSET score (28.8 vs 16.8; P < .001), checklist score (12.6
      vs 7.1; P < .001), and ASSET Safety score (3.9 vs 2.6; P < .001). CONCLUSION:
      These results demonstrate that low-fidelity ankle arthroscopy simulation training
      can improve basic surgical skills, efficiency of movement, and anatomic
      recognition. The results suggest greater patient safety during ankle arthroscopy
      following simulation training. LEVEL OF EVIDENCE: Level I, prospective
      comparative study.

PMID- 25761851
TI  - Forklift-Related Crush Injuries of the Foot and Ankle.
AB  - BACKGROUND: Forklift-related crush injuries of the foot and ankle are relatively
      common in cities with shipping and construction industries. There is a paucity of
      literature on the incidence and sequelae of such injuries. We aimed to describe
      the incidence, patterns of injuries, sequelae, and morbidity associated with this
      type of injury. METHODS: A retrospective review of all patients with forklift
      related crush injuries of the foot and ankle for 4 years was conducted. Patients'
      demographics, mechanisms and patterns of injury, fracture type, compartment
      syndrome, number of reconstructive operations, operative details, length of
      hospital stay, medical leave, repeat evaluation in emergency room, and
      complications were recorded and analyzed. RESULTS: There were 113 (2.17%)
      patients with forklift-related crush injuries out of 5209 patients seen in our
      institution for injuries of the foot and ankle. Crush injury from the wheels of
      the forklift truck was the most common mechanism at 71 (62.8%) patients. The
      forefoot was the most commonly injured region, followed by the midfoot, hindfoot,
      and ankle, with almost one-third (28.3%) of the patients having multiple injuries
      to the foot. Nine (8%) had open fractures, while 5 (4.4%) had compartment
      syndromes. Forty (35.4%) patients required hospitalization, and 35 (87.5%) of
      those hospitalized required operative intervention. Those who had surgery were
      more likely to have complications compared with those who did not require
      operative intervention (16 [45.7%] of 35 patients vs 7 [9%] of 78 patients; P <
      .05) and more likely to require longer medical leave (mean, 183 vs 30 days, P <
      .05). CONCLUSION: Forklift-related crush injuries of the foot and ankle are
      increasingly common in industrialized cities. The forefoot is commonly affected
      with involvement of multiple regions. Up to one-third of affected patients
      required hospitalization and multiple operative interventions resulting in loss
      of productivity, income, and significant morbidity. The possibility of residual
      disabilities must be clearly defined to the patients and their employers to
      manage potential workplace limitations and long-term expectations. LEVEL OF
      EVIDENCE: Level IV retrospective case series.

PMID- 25761852
TI  - Jump Landing Biomechanics During a Laboratory Recorded Recurrent Ankle Sprain.

PMID- 25761853
TI  - Effect of Intraoperative Three-Dimensional Imaging During the Reduction and
      Fixation of Displaced Calcaneal Fractures on Articular Congruence and Implant
      Fixation.
AB  - BACKGROUND: Operative treatment of displaced calcaneal fractures should restore
      joint congruence, but conventional fluoroscopy is unable to fully visualize the
      subtalar joint. We questioned whether intraoperative 3-dimensional (3D) imaging
      would aid in the reduction of calcaneal fractures, resulting in improved
      articular congruence and implant positioning. METHOD: Sixty-two displaced
      calcaneal fractures were operated on using standard fluoroscopic views. When the
      surgeon had achieved a satisfactory reduction, an intraoperative 3D scan was
      conducted, malreductions or implant imperfections were revised, the calcaneus was
      rescanned, and this sequence was repeated until the optimal operative result was
      achieved. RESULTS: Five fractures underwent 1 intraoperative scan, 39 fractures
      underwent 2 scans, 13 fractures underwent 3 scans, and 5 fractures underwent 4
      scans. The average number of scans was 2.3. Intraoperative scanning led to re
      reduction and improvement of reduction in 13 fractures, change of plate position
      in 1 patient, optimizing of the screw directions in 5 fractures, and shortening
      of screws that were intra-articular or protruding medially in 6 fractures. The
      postoperative articular displacement was 0 mm in 69% of the Sanders type 2
      fractures and 57% of the Sanders type 3 fractures. Operation duration averaged
      118 minutes, and there were no reoperations due to misplaced screws or plates.
      The average absorbed radiation dose per patient was 288 mGy.cm. CONCLUSION:
      Intraoperative 3D imaging improved the articular reduction of the posterior facet
      and secured optimal implant position in displaced calcaneal fractures. Radiation
      dose to the patient was less than that of a normal foot computed tomography scan.
      LEVEL OF EVIDENCE: Level IV, case series.

PMID- 25761854
TI  - Mortality of acute mesenteric ischemia remains unchanged despite significant
      increase in utilization of endovascular techniques.
AB  - INTRODUCTION: In this study, we evaluated if increase in utilization of
      endovascular surgery has affected in-hospital mortality rates among patients with
      acute mesenteric ischemia. METHODS: The National Inpatient Sample (2003-2011) was
      queried for acute mesenteric ischemia using ICD-9 code for acute mesenteric
      ischemia (557.1). This cohort was divided into patients treated with open
      vascular surgery (open vascular group) and by endovascular therapies
      (endovascular group) based on the ICD-9CM procedure codes. Multivariable logistic
      regression was used to determine temporal trend for mortality while adjusting for
      confounding variables. RESULTS: There was 1.45-fold increase in utilization of
      endovascular techniques in this study. In-hospital mortality rate, total median
      charges and length of stay were significantly lower among the endovascular group
      than the open vascular group despite having significantly higher Elixhauser
      comorbidities index (3 +/- 0.1 vs. 2.7 +/- 0.1, p = .003). Over the course of the
      study period, there was no change in the overall mortality rate despite higher
      endovascular utilization. Factors associated with increased mortality included
      age, open surgical repair (Odds ratio: 1.45, 95% Confidence Interval: 1.10-1.91,
      p = .016) and bowel resection Odds ratio: 2.88, 95% Confidence Interval: 2.01
      4.12). CONCLUSION: The mortality rate for acute mesenteric ischemia remains
      unchanged throughout this contemporary study. Open surgical intervention, bowel
      resection and age were associated with increased mortality. Endovascular group
      patients had better survival despite higher morbidity indices.

PMID- 25761855
TI  - Impairment of erectile function after elective repair of abdominal aortic
      aneurysm.
AB  - The purpose of the present study was to compare the functional change of erectile
      dysfunction after endovascular repair (EVAR) and open repair (OR) of abdominal
      aortic aneurysm.Between April 2009 and December 2011, male patients admitted for
      elective treatment of an asymptomatic infrarenal abdominal aortic aneurysm were
      included. The erectile function was evaluated by using a validated KEED
      questionnaire. All patients filled out the questionnaire preoperatively and
      postoperatively after one year.The number of patients with an increase of
      erectile dysfunction was 8 (26.6%) to 16 (53.3%) in open repair group vs. 30
      (42.6%) to 40 (58.8%) in endovascular aneurysm repair. There was no statistically
      significant difference between open repair and endovascular aneurysm repair
      groups in order of new incidence of erectile dysfunction (p = 0.412). The study
      showed an increase in the mean value of Erectile Dysfunction -Score
      postoperatively in both the groups as well.The present study showed an increase
      of erectile dysfunction postoperatively, but the difference between the two
      groups was not statistically significant. 

PMID- 25761857
TI  - Green synthesis of copper nanoparticles by Citrus medica Linn. (Idilimbu) juice
      and its antimicrobial activity.
AB  - We report an eco-friendly method for the synthesis of copper nanoparticles
      (CuNPs) using Citron juice (Citrus medica Linn.), which is nontoxic and cheap.
      The biogenic copper nanoparticles were characterized by UV-Vis spectrophotometer
      showing a typical resonance (SPR) at about 631 nm which is specific for CuNPs.
      Nanoparticles tracking analysis by NanoSight-LM20 showed the particles in the
      range of 10-60 nm with the concentration of 2.18 * 10(8) particles per ml. X-ray
      diffraction revealed the FCC nature of nanoparticles with an average size of 20
      nm. The antimicrobial activity of CuNPs was determined by Kirby-Bauer disk
      diffusion method against some selected species of bacteria and plant pathogenic
      fungi. It was reported that the synthesized CuNPs demonstrated a significant
      inhibitory activity against Escherichia coli followed by Klebsiella pneumoniae,
      Pseudomonas aeruginosa, Propionibacterium acnes and Salmonella typhi. Among the
      plant pathogenic fungi tested, Fusarium culmorum was found to be most sensitive
      followed by F. oxysporum and F. graminearum. The novelty of this work is that for
      the first time citron juice was used for the synthesis of CuNPs.

PMID- 25761856
TI  - Addressing limitations in observational studies of the association between
      glucose-lowering medications and all-cause mortality: a review.
AB  - A growing body of observational literature on the association between glucose
      lowering treatments and all-cause mortality has been accumulating in recent
      years. However, many investigations present designs or analyses that inadequately
      address the methodological challenges involved. We conducted a systematic search
      with a non-systematic extension to identify observational studies published
      between 2000 and 2012 that evaluated the effects of glucose-lowering medications
      on all-cause mortality. We reviewed these studies and assessed the design and
      analysis methods used, with a focus on their ability to address specific
      methodological challenges. We described these methodological issues and their
      potential impact on observed associations, providing examples from the reviewed
      literature, and suggested possible approaches to manage these methodological
      challenges. We evaluated 67 publications of observational studies evaluating the
      association between glucose-lowering treatments and all-cause mortality. The
      identified methodological challenges included trade-offs associated with the
      outcome of all-cause mortality, incorrect temporal sequencing in administrative
      databases, inadequate treatment of time-varying hazards and treatment duration
      effects, unclear definition of the exposure risk window, improper handling of
      time-varying exposures, and incomplete accounting for confounding by indication.
      Most of these methodological challenges may be adequately addressed through the
      application of appropriate methods. Observational research plays an increasingly
      important role in assessing the clinical effects of diabetes therapy. The
      implementation of suitable research methods can reduce the potential for spurious
      findings, and thus the risk of misleading the medical community about benefits
      and harms of diabetes therapy. 

PMID- 25761858
TI  - Serine protease HtrA1 as an inhibitor on proliferation invasion and migration of
      gastric cancer.
AB  - HtrA1, as serine protease lower expressed in various human solid tumors, can down
      regulate cell growth and proliferation. In this study, we focus on whether
      overexpressed HtrA1 can inhibit the growth of gastric cancer in vitro. This study
      found the HtrA1 is lower expressed in gastric cancer tissue than in normal
      gastric tissue. When HtrA1 is highly expressing with recombinant plasmid in
      gastric cancer cell lines SGC-7901 and AGS, it weakened cell proliferation,
      invasion, and migration in vitro. These data suggested that HtrA1 as an inhibitor
      in gastric cancer cells resulted in anti-proliferation, reduced invasion,
      decreased migration, and suppressed growth and may be an effective molecular
      targets on gastric cancer treatment. 

PMID- 25761859
TI  - Fluid dynamics of liquid egg products.
AB  - The rheological behavior of liquid egg products (egg yolk, egg white, and whole
      liquid egg) was studied using a concentric cylinder viscometer. Eggs of three
      poultry specimens were used: hen (Isa Brown), Japanese quail (Coturnix japonica),
      and goose (Anser anser f. domestica). Rheological behavior was pseudoplastic and
      flow curves fitted by the power law model (Herschel-Bulkley and Ostwald-De
      Waele). The meaning of rheological parameters on friction factors and velocity
      profiles during flow of liquid egg products in tube has been shown. 

PMID- 25761861
TI  - Tropicihabitans flavus gen. nov., sp. nov., a new member of the family
      Cellulomonadaceae.
AB  - Two novel Gram-stain positive actinobacteria, designated PS-14-16(T) and RS-7-1,
      were isolated from the rhizosphere of a mangrove and sea sediment, respectively,
      and their taxonomic positions were investigated by a polyphasic approach. Both
      strains were observed to form vegetative hyphae in the early phase of growth but
      the hyphae eventually fragment into short rods to coccoid cells. The
      peptidoglycan type of both strains was found to be A4alpha. Their predominant
      menaquinone was identified as MK-9(H4) and the major fatty acid as anteiso
      C(15:0). The DNA G+C content was determined to be 68.4-68.5 mol%. 16S rRNA gene
      sequencing revealed that strains PS-14-16(T) and RS-7-1 were related to members
      of the family Cellulomonadaceae. Their nearest phylogenetic neighbour was found
      to be Sediminihabitans luteus, which is currently the only species of the genus
      Sediminihabitans, with a similarity of 97.94%. However, strains PS-14-16(T) and
      RS-7-1 were distinguishable from the members of the genus Sediminihabitans and
      the other genera within the family Cellulomonadaceae in terms of chemotaxonomic
      characteristics and phylogenetic relationship. The results of DNA-DNA
      hybridization experiments indicated that strains PS-14-16(T) and RS-7-1 belong to
      the same species. Strains PS-14-16(T) and RS-7-1 are concluded to represent a
      novel genus and species of the family Cellulomonadaceae, for which the name
      Tropicihabitans flavus gen. nov., sp. nov. is proposed. The type strain of T.
      flavus is PS-14-16(T) (=NBRC 110109(T) = IanCC A 516(T)). [corrected].

PMID- 25761860
TI  - Streptomyces alkaliphilus sp. nov., isolated from sediments of Lake Elmenteita in
      the Kenyan Rift Valley.
AB  - A novel strain, designated No. 7(T), was isolated from a sediment sample
      collected from the alkaline, saline Lake Elmenteita located in the Kenyan Rift
      Valley. The optimal growth for the strain was found to be at temperature 30-35 
      degrees C, at pH 8.0-12.0 in the presence of 7.0-10.0 % (w/v) NaCl. The strain
      was observed to form a light green beige abundant aerial mycelium on Horikoshi 1
      agar and to have morphological and chemotaxonomic characteristics typical of
      members of the genus Streptomyces. The peptidoglycan was found to contain LL
      diaminopimelic acid as the diamino acid, with no diagnostic sugars identified.
      The predominant menaquinone was identified as MK-9(H6). The main polar lipids
      were identified as diphosphatidylglycerol, phosphatidylethanolamine,
      phosphatidylinositol and an unknown phospholipid. Cellular fatty acids were found
      to consist of saturated branched-chain acids with iso-C(15:0), anteiso-C(15:0),
      iso-C(16:0) and anteiso-C(17:0) acids predominating. The type strain had a
      genomic DNA G+C content of 72.8 mol% and formed a distinct phyletic line within
      the genus Streptomyces. Based on the chemotaxonomic results, 16S rRNA gene
      sequence analysis and the low DNA-DNA hybridization value with the type strain of
      Streptomyces calidiresistens, it is proposed that strain No. 7(T) (= DSM 42118 =
      CECT 8549) represents a novel species, Streptomyces alkaliphilus. The INSDC
      accession number for the 16S rRNA gene sequence of strain No. 7(T) is KF976730.

PMID- 25761862
TI  - Occultifur kilbournensis f.a. sp. nov., a new member of the Cystobasidiales
      associated with maize (Zea mays) cultivation.
AB  - During a study of microorganisms associated with maize (Zea mays) cultivation,
      yeasts were isolated from overwintered stalks, cobs and surrounding soil, which
      were collected from an agricultural field in south-central Illinois, USA.
      Predominant among isolates were two species of Cryptococcus (Cr. flavescens, Cr.
      magnus) and a red yeast that D1/D2 LSU rRNA gene sequences revealed to be a new
      species of the basidiomycete yeast genus Occultifur. The species, which was not
      detected in the same field during the growing season, is described here as
      Occultifur kilbournensis (MycoBank number MB 811259; type strain NRRL Y-63695,
      CBS 13982, GenBank numbers, D1/D2 LSU rRNA gene, KP413160, ITS, KP413162;
      allotype strain NRRL Y-63699, CBS 13983). Mixture of the type and allotype
      strains resulted in formation of hyphae with clamp connections and a small number
      of apparent basidia following incubation on 5% malt extract agar at 15  degrees C
      for 2 months. In view of the uncertainty of the life cycle, the new species is
      being designated as forma asexualis. From analysis of D1/D2 and ITS nucleotide
      sequences, the new species is most closely related to Occultifur externus.

PMID- 25761864
TI  - Endoscope-assisted resection of calcified thoracic disc herniations.
AB  - PURPOSE: Resection of calcified thoracic disc herniations carries significant
      risks of neurological worsening, particularly in case of concomitant central
      location. Transthoracic approaches are a first-choice option to avoid spinal cord
      manipulation but entail drawbacks such as postoperative pain and the risk of
      bronchopulmonary complications. The purpose of this report is to describe a novel
      approach to resect calcified herniations, even centrally located, from a
      posterior perspective. METHODS: Unilateral lamino-arthrectomy is performed,
      uncovering few millimeters of the disc space beside the dura. Following
      discectomy and drilling of the vertebral endplates, an angled endoscope is
      introduced allowing resection of the calcified herniation through an anterior
      perspective. The spinal cord can now be decompressed with a no-touch technique.
      Each maneuver aimed at resecting the calcified mass up to the contralateral side
      can be done under visual control. RESULTS: The technique was used in two
      patients. The first was a 38-year-old man with a calcified mediolateral T9-T10
      disc herniation and mild myelopathic symptoms. The second patient was a 73-year
      old obese woman, with a T6-T7 central, calcified disc herniation and severe
      compression myelopathy. In both cases, complete decompression of the spinal cord
      could be achieved and rapid neurological recovery was observed postoperatively.
      No surgery-related complications were observed. CONCLUSIONS: The endoscope
      assisted posterior approach afforded safe and complete resection of calcified
      discs. The technique is particularly useful for central disc herniations, where
      transthoracic approaches are normally deemed mandatory.

PMID- 25761863
TI  - Systemic inflammatory response and serum lipopolysaccharide levels predict
      multiple organ failure and death in alcoholic hepatitis.
AB  - Alcoholic hepatitis (AH) frequently progresses to multiple organ failure (MOF)
      and death. However, the driving factors are largely unknown. At admission,
      patients with AH often show criteria of systemic inflammatory response syndrome
      (SIRS) even in the absence of an infection. We hypothesize that the presence of
      SIRS may predispose to MOF and death. To test this hypothesis, we studied a
      cohort including 162 patients with biopsy-proven AH. The presence of SIRS and
      infections was assessed in all patients, and multivariate analyses identified
      variables independently associated with MOF and 90-day mortality. At admission,
      32 (19.8%) patients were diagnosed with a bacterial infection, while 75 (46.3%)
      fulfilled SIRS criteria; 58 patients (35.8%) developed MOF during
      hospitalization. Short-term mortality was significantly higher among patients who
      developed MOF (62.1% versus 3.8%, P < 0.001). The presence of SIRS was a major
      predictor of MOF (odds ratio = 2.69, P = 0.025) and strongly correlated with
      mortality. Importantly, the course of patients with SIRS with and without
      infection was similar in terms of MOF development and short-term mortality.
      Finally, we sought to identify serum markers that differentiate SIRS with and
      without infection. We studied serum levels of high-sensitivity C-reactive
      protein, procalcitonin, and lipopolysaccharide at admission. All of them
      predicted mortality. Procalcitonin, but not high-sensitivity C-reactive protein,
      serum levels identified those patients with SIRS and infection.
      Lipopolysaccharide serum levels predicted MOF and the response to prednisolone.
      CONCLUSION: In the presence or absence of infections, SIRS is a major determinant
      of MOF and mortality in AH, and the mechanisms involved in the development of
      SIRS should be investigated; procalcitonin serum levels can help to identify
      patients with infection, and lipopolysaccharide levels may help to predict
      mortality and the response to steroids.

PMID- 25761865
TI  - Skewed Fc glycosylation profiles of anti-proteinase 3 immunoglobulin G1
      autoantibodies from granulomatosis with polyangiitis patients show low levels of
      bisection, galactosylation, and sialylation.
AB  - Granulomatosis with polyangiitis (GPA) is associated with circulating
      immunoglobulin (Ig) G anti-proteinase 3 specific (anti-PR3) anti-neutrophil
      cytoplasm antibodies (ANCA), which activate cytokine primed neutrophils via
      Fcgamma receptors. ANCA are class switched IgG antibodies implying T cell help in
      their production. Glycosylation of IgG Fc, under the control of T cell cytokines,
      determines the interaction between IgG and its receptors. Previous studies have
      reported aberrant glycosylation of Ig Fc in GPA patients. We investigated whether
      aberrant Fc glycosylation was present on anti-PR3 ANCA as well as whole IgG
      subclass preparations compared to healthy controls and whether this correlated
      with Birmingham vasculitis activity scores (BVAS), serum cytokines, and time to
      remission. Here, IgG Fc glycosylation of GPA patients and controls and anti-PR3
      ANCA Fc glycosylation were determined by mass spectrometry of glycopeptides. IgG1
      and IgG2 subclasses from GPA patients showed reduced galactosylation,
      sialylation, and bisection compared to healthy controls. Anti-PR3 IgG1 ANCA Fc
      galactosylation, sialylation, and bisection were reduced compared to total IgG1
      in GPA. Galactosylation of anti-PR3 ANCA Fc correlated with inflammatory
      cytokines and time to remission but not BVAS. Bisection of anti-PR3 ANCA Fc
      correlated with BVAS. Total IgG1 and anti-PR3 IgG1 Fc galactosylation were weakly
      correlated, while bisection of IgG1 and anti-PR3 showed no correlation. Our data
      indicate that aberrant ANCA galactosylation may be driven in an antigen-specific
      manner. 

PMID- 25761866
TI  - Prolonged Outbreak of Mycobacterium chimaera Infection After Open-Chest Heart
      Surgery.
AB  - BACKGROUND: Invasive Mycobacterium chimaera infections were diagnosed in 2012 in
      2 heart surgery patients on extracorporeal circulation. We launched an outbreak
      investigation to identify the source and extent of the potential outbreak and to
      implement preventive measures. METHODS: We collected water samples from operating
      theaters, intensive care units, and wards, including air samples from operating
      theaters. Mycobacterium chimaera strains were characterized by randomly amplified
      polymorphic DNA polymerase chain reaction (RAPD-PCR). Case detection was
      performed based on archived histopathology samples and M. chimaera isolates since
      2006, and the patient population at risk was prospectively surveyed. RESULTS: We
      identified 6 male patients aged between 49 and 64 years with prosthetic valve
      endocarditis or vascular graft infection due to M. chimaera, which became
      clinically manifest with a latency of between 1.5 and 3.6 years after surgery.
      Mycobacterium chimaera was isolated from cardiac tissue specimens, blood
      cultures, or other biopsy specimens. We were able also to culture M. chimaera
      from water circuits of heater-cooler units connected to the cardiopulmonary
      bypass, and air samples collected when the units were in use. RAPD-PCR
      demonstrated identical patterns among M. chimaera strains from heater-cooler unit
      water circuits and air samples, and strains in 2 patient clusters. CONCLUSIONS:
      The epidemiological and microbiological features of this prolonged outbreak
      provided evidence for the airborne transmission of M. chimaera from contaminated
      heater-cooler unit water tanks to patients during open-heart surgery.

PMID- 25761867
TI  - Hepatitis C virus therapeutic development: in pursuit of "perfectovir".
AB  - The next decade will be a crucial period in the public health response to
      hepatitis C virus (HCV) infection. The rapid development of direct-acting
      antiviral (DAA) therapy for HCV infection has brought considerable optimism to
      the HCV sector, with the realistic hope that therapeutic intervention will soon
      provide near-optimal efficacy with well-tolerated short-duration, all-oral
      regimens. As the zenith in HCV therapeutic development approaches, there remain
      several key obstacles to the broad implementation of interferon-free DAA
      regimens. The extent of HCV screening and disease assessment, global and national
      public health prioritization, and drug pricing will determine the potential
      impact on disease burden derived from introduction of these exciting new HCV
      therapies. Public health partnerships and advocacy will be crucial to remove
      barriers to enhanced HCV treatment access. 

PMID- 25761870
TI  - Prevalence of colorectal neoplasm in Chinese patients with high-risk coronary
      artery disease classified by the Asia-Pacific Colorectal Screening score.
AB  - OBJECTIVE: The aim of this study was to investigate the prevalence of colorectal
      neoplasms in patients coronary artery disease (CAD) with or without a family
      history of colorectal cancer (CRC). METHODS: In this cross-sectional study,
      individuals with suspected CAD in the absence of cancer-related symptoms
      underwent coronary angiography for the first time, and were divided into CAD and
      non-CAD groups. Colonoscopy was performed in individuals at high-risk tier based
      on their Asia-Pacific colorectal screening (APCS) score. Their waist
      circumference (WC), height and body weight were measured. RESULTS: There were 634
      of 1157 individuals at a high risk of developing advanced colorectal neoplasms,
      91.0% (577/634) of whom were male smokers. The proportion of CAD patients in the
      high-risk tier was 81.5% (517/634), while the prevalences of adenomas (32.1% vs
      22.2%, P < 0.05) and advanced adenomas (14.7% vs 8.5%, P < 0.05) were
      significantly higher in the CAD group than in the non-CAD group. After 83
      individuals with a family history of CRC were excluded, only the prevalence of
      adenomas was still significantly higher in the CAD group than in the non-CAD
      group (25.5% vs 16.0%, P < 0.01). Body mass index (BMI) >= 25 kg/m(2) was
      correlated with the occurrence of adenomas (OR 2.133, 95% CI 1.219-3.730, P =
      0.008) in CAD patients. CONCLUSIONS: Even in the absence of family history of
      CRC, CAD patients at a high risk of developing advanced colorectal neoplasms
      classified by the APCS score still showed a remarkably high prevalence of
      colorectal adenomas. Moreover, the association between the occurrence of adenomas
      and CAD was stronger in overweight (BMI >= 25 kg/m(2)) individuals.

PMID- 25761868
TI  - Weight change after antiretroviral therapy and mortality.
AB  - BACKGROUND: Weight gain after antiretroviral therapy (ART) initiation is common,
      but its implication for mortality is unknown. We evaluated weight change in the
      first year after ART initiation and its association with subsequent mortality.
      METHODS: Human immunodeficiency virus-infected patients from the Veterans Aging
      Cohort Study (VACS) who initiated ART between 2000 and 2008, with weight recorded
      at baseline and 1 year later, were followed another 5 years for mortality.
      Baseline body mass index (BMI) was classified as underweight (<18.5 kg/m(2)),
      normal (18.5-24.9 kg/m(2)), overweight (25-29.9 kg/m(2)), and obese (>=30
      kg/m(2)). We used multivariable Cox models to assess mortality risk with
      adjustment for disease severity using the VACS Index. RESULTS: The sample
      consisted of 4184 men and 127 women with a mean age of 47.9 +/- 10.0 years. After
      1 year of ART, median weight change was 5.9 pounds (2.7 kg) (interquartile range,
      -2.9 to 17.0 pounds, -1.3 to 7.7 kg). Weight gain after ART initiation was
      associated with lower mortality among underweight and normal-weight patients. A
      minimum threshold of 10- to 19.9-pound (4.5 to 9.0 kg) weight gain was beneficial
      for normal-weight patients (hazard ratio, 0.56; 95% confidence interval, .41
      .78), but there was no clear benefit to weight gain for overweight/obese
      patients. Baseline weight, CD4 cell count status, and hemoglobin level were
      strongly associated with weight gain. Risk for weight gain was higher among those
      with greater disease severity, regardless of weight at initiation. CONCLUSIONS:
      The survival benefits of weight gain after ART initiation are dependent on
      starting BMI. Weight gain after ART is associated with lower mortality for those
      who are not initially overweight.

PMID- 25761869
TI  - Development of a metabolic biosignature for detection of early Lyme disease.
AB  - BACKGROUND: Early Lyme disease patients often present to the clinic prior to
      developing a detectable antibody response to Borrelia burgdorferi, the etiologic
      agent. Thus, existing 2-tier serology-based assays yield low sensitivities (29%
      40%) for early infection. The lack of an accurate laboratory test for early Lyme
      disease contributes to misconceptions about diagnosis and treatment, and
      underscores the need for new diagnostic approaches. METHODS: Retrospective serum
      samples from patients with early Lyme disease, other diseases, and healthy
      controls were analyzed for small molecule metabolites by liquid chromatography
      mass spectrometry (LC-MS). A metabolomics data workflow was applied to select a
      biosignature for classifying early Lyme disease and non-Lyme disease patients. A
      statistical model of the biosignature was trained using the patients' LC-MS data,
      and subsequently applied as an experimental diagnostic tool with LC-MS data from
      additional patient sera. The accuracy of this method was compared with standard 2
      tier serology. RESULTS: Metabolic biosignature development selected 95 molecular
      features that distinguished early Lyme disease patients from healthy controls.
      Statistical modeling reduced the biosignature to 44 molecular features, and
      correctly classified early Lyme disease patients and healthy controls with a
      sensitivity of 88% (84%-95%), and a specificity of 95% (90%-100%). Importantly,
      the metabolic biosignature correctly classified 77%-95% of the of serology
      negative Lyme disease patients. CONCLUSIONS: The data provide proof-of-concept
      that metabolic profiling for early Lyme disease can achieve significantly greater
      (P < .0001) diagnostic sensitivity than current 2-tier serology, while retaining
      high specificity.

PMID- 25761871
TI  - 3D high-resolution diffusion-weighted MRI at 3T: Preliminary application in
      prostate cancer patients undergoing active surveillance protocol for low-risk
      prostate cancer.
AB  - PURPOSE: To improve spatial resolution and image quality of diffusion-weighted
      (DW) MRI in detecting low-risk prostate cancer (lrPC) in patients undergoing
      active surveillance protocol (AS-PC), we propose the application of a diffusion
      prepared balanced steady-state free precession (bSSFP) technique capable of
      multishot acquisition. METHODS: Diffusion-prepared bSSFP was compared with single
      shot DW echo planar imaging (SS-DW-EPI) at two prescribed resolutions (2.1 * 2.1
      * 3.5mm(3) , 0.9 * 0.9 * 3.5 mm(3) ) in nine healthy subjects and nine AS-PC
      patients. Geometric distortion and susceptibility artifacts were quantitatively
      assessed in all subjects. In AS-PC patients, lesion detection via blinded
      multiparametric MRI including T1-weighted, T2-weighted, dynamic contrast-enhanced
      imaging, and along with either of two DW methods were evaluated against 12-point
      biopsy. RESULTS: Geometric distortion and susceptibility artifacts were
      significantly less for diffusion-prepared bSSFP at both prescribed spatial
      resolutions than SS-DW-EPI. Apparent diffusion coefficients of healthy prostate
      tissue were concordant between the two DW methods at both spatial resolutions. In
      AS-PC patients, multiparametric MRI with diffusion-prepared bSSFP had greater
      sensitivity (94%, 63%), accuracy (76%, 67%), positive-predictive value (54%,
      48%), negative-predictive value (97%, 82%), and area under the curve (0.80, 0.67)
      than with SS-DW-EPI. CONCLUSIONS: The proposed diffusion-prepared technique with
      higher spatial resolution and improved image quality over SS-DW-EPI resulted in
      better multiparametric MRI detection of lrPC in AS-PC patients.

PMID- 25761872
TI  - Surgical menopause initiates molecular changes that do not result in mechanical
      changes in normal and healing ligaments.
AB  - OBJECTIVES: Ligaments which heal spontaneously have a healing process that is
      similar to skin wound healing. Menopause impairs skin wound healing and may
      likewise impair ligament healing. Our purpose in this study was to investigate
      the effect of surgical menopause on ligament healing in a rabbit medial
      collateral ligament model. METHODS: Surgical menopause was induced with
      ovariohysterectomy surgery in adult female rabbits. Ligament injury was created
      by making a surgical gap in the midsubstance of the medial collateral ligament.
      Ligaments were allowed to heal for six or 14 weeks in the presence or absence of
      oestrogen before being compared with uninjured ligaments. Molecular assessment
      examined the messenger ribonucleic acid levels for collagens, proteoglycans,
      proteinases, hormone receptors, growth factors and inflammatory mediators.
      Mechanical assessments examined ligament laxity, total creep strain and failure
      stress. RESULTS: Surgical menopause in normal medial collateral ligaments
      initiated molecular changes in all the categories evaluated. In early healing
      medial collateral ligaments, surgical menopause resulted in downregulation of
      specific collagens, proteinases and inflammatory mediators at 6 weeks of healing,
      and proteoglycans, growth factors and hormone receptors at 14 weeks of healing.
      Surgical menopause did not produce mechanical changes in normal or early healing
      medial collateral ligaments. With or without surgical menopause, healing
      ligaments exhibited increased total creep strain and decreased failure stress
      compared with uninjured ligaments. CONCLUSIONS: Surgical menopause did not affect
      the mechanical properties of normal or early healing medial collateral ligaments
      in a rabbit model. The results in this preclinical model suggest that menopause
      may result in no further impairment to the ligament healing process. Cite this
      article: Bone Joint Res 2015;4:38-44.

PMID- 25761873
TI  - Chlamydia caviae infection alters abundance but not composition of the guinea pig
      vaginal microbiota.
AB  - In humans, the vaginal microbiota is thought to be the first line of defense
      again pathogens including Chlamydia trachomatis. The guinea pig has been
      extensively used as a model to study chlamydial infection because it shares
      anatomical and physiological similarities with humans, such as a squamous vaginal
      epithelium as well as some of the long-term outcomes caused by chlamydial
      infection. In this study, we aimed to evaluate the guinea pig-C. caviae model of
      genital infection as a surrogate for studying the role of the vaginal microbiota
      in the early steps of C. trachomatis infection in humans. We used culture
      independent molecular methods to characterize the relative and absolute abundance
      of bacterial phylotypes in the guinea pig vaginal microbiota in animals non
      infected, mock-infected or infected by C. caviae. We showed that the guinea pig
      and human vaginal microbiotas are of different bacterial composition and
      abundance. Chlamydia caviae infection had a profound effect on the absolute
      abundance of bacterial phylotypes but not on the composition of the guinea pig
      vaginal microbiota. Our findings compromise the validity of the guinea pig-C.
      caviae model to study the role of the vaginal microbiota during the early steps
      of sexually transmitted infection. 

PMID- 25761874
TI  - Fisetin exerts antihyperalgesic effect in a mouse model of neuropathic pain:
      engagement of spinal serotonergic system.
AB  - Fisetin, a natural flavonoid, has been shown in our previous studies to exert
      antidepressant-like effect. As antidepressant drugs are clinically used to treat
      chronic neuropathic pain, this work aimed to investigate the potential
      antinociceptive efficacies of fisetin against neuropathic pain and explore
      mechanism(s). We subjected mice to chronic constriction injury (CCI) by loosely
      ligating the sciatic nerves, and Hargreaves test or von Frey test was used to
      assess thermal hyperalgesia or mechanical allodynia, respectively. Chronic
      fisetin treatment (5, 15 or 45 mg/kg, p.o.) ameliorated thermal hyperalgesia (but
      not mechanical allodynia) in CCI mice, concomitant with escalated levels of
      spinal monoamines and suppressed monoamine oxidase (MAO)-A activity. The
      antihyperalgesic action of fisetin was abolished by chemical depletion of spinal
      serotonin (5-HT) but potentiated by co-treatment with 5-HTP, a precursor of 5-HT.
      Moreover, intraperitoneal (i.p.) or intrathecal (i.t.) co-treatment with 5-HT7
      receptor antagonist SB-258719 completely abrogated fisetin's antihyperalgesia.
      These findings confirm that chronic fisetin treatment exerts antinociceptive
      effect on thermal hyperalgesia in neuropathic mice, with spinal serotonergic
      system (coupled with 5-HT7) being critically involved. Of special benefit,
      fisetin attenuated co-morbidly behavioral symptoms of depression and anxiety
      (evaluated in forced swim test, novelty suppressed feeding test and light-dark
      test) evoked by neuropathic pain. 

PMID- 25761875
TI  - Macrophages are needed in the progression of tuberculosis into lung cancer.
AB  - Although the association of tuberculosis (TB) and the development of lung
      carcinoma (LC) has been acknowledged, the underlying mechanism remains not
      clarified. Since sustained and repeated local inflammation and tissue remodeling
      have been suggested to be responsible for the high incidence of developing CL
      from TB, we hypothesize that macrophages may play a critical role in the process.
      To prove it, we induced TB in mice by injection of virulent Mycobacterium
      tuberculosis (MTB). Then the mice were allotted into two groups. One group
      received weekly tail vein injection of 20 MUg saporin-conjugated antibody against
      the pan-macrophage surface marker CD11b to eliminate macrophages, while the other
      group received injection of control IgG in the same frequency. Six months later,
      the development of LC was determined by histology. We found that the occurrence
      of LC in TB mice that received macrophage depletion was significantly lower than
      those in control TB mice without macrophage intervention. These data suggest that
      macrophages may promote the progression of TB into LC.

PMID- 25761877
TI  - Prognostic significance of the recurrence pattern and risk factors for recurrence
      in patients with proximal gastric cancer who underwent curative gastrectomy.
AB  - Proximal gastric cancer has a high propensity of early recurrence after curative
      resection due to high incidence of lymph node involvement. In the present study,
      we aimed to investigate the pattern and time of recurrence and to evaluate the
      risk factors for recurrence of patients with proximal gastric cancer. Between
      2005 and 2013, 99 patients with recurrent proximal gastric cancer who underwent
      radical gastrectomy were retrospectively analyzed. The prognostic significance of
      the pattern and the time of recurrence and the relationship between the pattern
      of recurrence and the other clinicopathological factors were evaluated. The
      median time to recurrence was 24 months; 45.5 % of patients relapsed within 2
      years. Forty-three (43.4 %) patients indicated hematogenous recurrence and 41
      (41.4 %) patients revealed peritoneal recurrence with the most predominant
      patterns. The median progression-free survival (PFS) time for patients with
      locoregional recurrence was significantly better than that of patients with
      peritoneal recurrences, hematogenous recurrences, and distant lymph nodes (32.2
      vs. 18.9 vs. 18.2 vs. 9.7 months, p = 0.005, respectively). Moreover, the median
      overall survival (OS) interval for patients with distant lymph nodes recurrence
      was significantly worse than that of patients with locoregional, peritoneal, and
      hematogenous recurrences (13.5 vs. 48.5 vs. 31.4 vs. 29.9 months, p = 0.006,
      respectively). The presence of lymph node metastasis (p = 0.004) and surgery type
      (p = 0.04) for PFS and the time of recurrence (p = 0.033), lymph node metastasis
      (p = 0.03), and surgery type (p = 0.04) for OS were found to be independent
      prognostic factors by multivariate analysis. Logistic regression analysis
      indicated that the presence of lymph node metastasis and surgery type were
      independent risk factors for predicting the occurrence of early recurrence (p =
      0.001, OR 0.48 and p = 0.028, OR 0.41, respectively). The median OS time of early
      recurrence patients was significantly shorter than that of patients with late
      recurrence (16.6 vs. 55.2 months, p < 0.001). Furthermore, proximal gastrectomy,
      poorly differentiated histology, advanced pT stage, and lymph node metastasis
      were significantly associated with early recurrence. Our results showed that
      lymph node metastasis and surgery type were independent risk factors for
      prediction of early recurrence in proximal gastric cancer. Thus, total
      gastrectomy with regional lymph node dissection may be a suitable treatment
      option for proximal gastric cancer patients with tumors that have high risk
      features for recurrence.

PMID- 25761876
TI  - COL11A1/(pro)collagen 11A1 expression is a remarkable biomarker of human invasive
      carcinoma-associated stromal cells and carcinoma progression.
AB  - The COL11A1 human gene codes for the alpha1 chain of procollagen 11A1 and mature
      collagen 11A1, an extracellular minor fibrillar collagen. Under regular
      conditions, this gene and its derived products are mainly expressed by
      chondrocytes and mesenchymal stem cells as well as osteoblasts. Normal epithelial
      cells and quiescent fibroblasts from diverse locations do not express them.
      Mesenchyme-derived tumors and related conditions, such as scleroderma and
      keloids, are positive for COL11A1/(pro)collagen 11A1 expression, as well as high
      grade human gliomas/glioblastomas. This expression is almost absent in benign
      pathological processes such as breast hyperplasia, sclerosing adenosis,
      idiopathic pulmonary fibrosis, cirrhosis, pancreatitis, diverticulitis, and
      inflammatory bowel disease. By contrast, COL11A1/(pro)collagen 11A1 is highly
      expressed by activated stromal cells of the desmoplastic reaction of different
      human invasive carcinomas, and this expression is correlated with carcinoma
      aggressiveness and progression, and lymph node metastasis. COL11A1 upregulation
      has been shown to be associated to TGF-beta1, Wnt, and Hh signaling pathways,
      which are especially active in cancer-associated stromal cells. At the front of
      invasive carcinomas, neoplastic epithelial cells, putatively undergoing
      epithelial-to-mesenchymal transition, and carcinoma-derived cells with highly
      metastatic capabilities, can express COL11A1. Thus, in established metastases,
      the expression of COL11A1/(pro)collagen 11A1 could rely on both the metastatic
      epithelial cells and/or the accompanying activated stromal cells.
      COL11A1/(pro)collagen 11A1 expression is a remarkable biomarker of human
      carcinoma-associated stromal cells and carcinoma progression. 

PMID- 25761878
TI  - MicroRNA-26b inhibits metastasis of osteosarcoma via targeting CTGF and Smad1.
AB  - Downregulation of miR-26b has been found in various cancers, but it has never
      been investigated in osteosarcoma. In this study, we demonstrated downregulation
      of miR-26b in osteosarcoma tissues, negatively correlated with the expression of
      connective tissue growth factor (CTGF) and Smad1. Luciferase reporter assay
      confirmed the interaction of miR-26b with the 3' untranslated regions (UTRs) of
      CTGF and Smad1. Transfection of miR-26b in osteosarcoma cells suppressed the
      expression of CTGF and Smad1, suggesting CTGF and Smad1 as direct targets of miR
      26b. Overexpression of miR-26b inhibited the migration of osteosarcoma cells,
      which was reversed by overexpression of CTGF or Smad1. Knockdown of CTGF by small
      interfering RNA (siRNA) interference blocked the activation of Smad1, ERK1/2, and
      MMP2, which was opposite to the overexpression of CTGF. Differently, Smad1 did
      not significantly affect CTGF level, but mediated ERK1/2 phosphorylation and MMP2
      activation. Furthermore, miR-26b inhibited lung metastasis of osteosarcoma in
      vivo. Our data indicated that downregulation of miR-26b in osteosarcoma elevated
      the levels of CTGF and Smad1, facilitating osteosarcoma metastasis.

PMID- 25761879
TI  - Functional roles of TRPV1 and TRPV4 in control of lower urinary tract activity:
      dual analysis of behavior and reflex during the micturition cycle.
AB  - The present study used a dual analysis of voiding behavior and reflex micturition
      to examine lower urinary tract function in transient receptor potential vanilloid
      (TRPV)1 knockout (KO) mice and TRPV4 KO mice. In metabolic cage experiments
      conducted under conscious conditions (i.e., voluntary voiding behavior), TRPV4 KO
      mice showed a markedly higher voiding frequency (VF; 19.3 +/- 1.2 times/day) and
      a smaller urine volume/voiding (UVV; 114 +/- 9 MUl) compared with wild-type (WT)
      littermates (VF: 5.2 +/- 0.5 times/day and UVV: 380 +/- 34 MUl). Meanwhile, TRPV1
      KO mice showed a similar VF to WT littermates (6.8 +/- 0.5 times/day) with a
      significantly smaller UVV (276 +/- 20 MUl). Water intake among these genotypes
      was the same, but TRPV4 KO mice had a larger urine output than the other two
      groups. In cystometrogram experiments conducted in decerebrate unanesthetized
      mice (i.e., reflex micturition response), no differences between the three groups
      were found in any cystometrogram variables, including voided volume, volume
      threshold for inducing micturition contraction, maximal voiding pressure, and
      bladder compliance. However, both TRPV1 KO and TRPV4 KO mice showed a significant
      number of nonvoiding bladder contractions (NVCs; 3.5 +/- 0.9 and 2.8 +/- 0.7
      contractions, respectively) before each voiding, whereas WT mice showed virtually
      no NVCs. These results suggest that in the reflex micturition circuit, a lack of
      either channel is involved in NVCs during bladder filling, whereas in the
      forebrain, it is involved in the early timing of urine release, possibly in the
      conscious response to the bladder instability. 

PMID- 25761880
TI  - Effects of moderate global maternal nutrient reduction on fetal baboon renal
      mitochondrial gene expression at 0.9 gestation.
AB  - Early life malnutrition results in structural alterations in the kidney,
      predisposing offspring to later life renal dysfunction. Kidneys of adults who
      were growth restricted at birth have substantial variations in nephron endowment.
      Animal models have indicated renal structural and functional consequences in
      offspring exposed to suboptimal intrauterine nutrition. Mitochondrial
      bioenergetics play a key role in renal energy metabolism, growth, and function.
      We hypothesized that moderate maternal nutrient reduction (MNR) would adversely
      impact fetal renal mitochondrial expression in a well-established nonhuman
      primate model that produces intrauterine growth reduction at term. Female baboons
      were fed normal chow diet or 70% of control diet (MNR). Fetal kidneys were
      harvested at cesarean section at 0.9 gestation (165 days gestation). Human
      Mitochondrial Energy Metabolism and Human Mitochondria Pathway PCR Arrays were
      used to analyze mitochondrially relevant mRNA expression. In situ protein content
      was detected by immunohistochemistry. Despite the smaller overall size, the fetal
      kidney weight-to-body weight ratio was not affected. We demonstrated fetal sex
      specific differential mRNA expression encoding mitochondrial metabolite transport
      and dynamics proteins. MNR-related differential gene expression was more evident
      in female fetuses, with 16 transcripts significantly altered, including 14
      downregulated and 2 upregulated transcripts. MNR impacted 10 transcripts in male
      fetuses, with 7 downregulated and 3 upregulated transcripts. The alteration in
      mRNA levels was accompanied by a decrease in mitochondrial protein cytochrome c
      oxidase subunit VIc. In conclusion, transcripts encoding fetal renal
      mitochondrial energy metabolism proteins are nutrition sensitive in a sex
      dependent manner. We speculate that these differences lead to decreased
      mitochondrial fitness that contributes to renal dysfunction in later life. 

PMID- 25761881
TI  - Aldosterone modulates thiazide-sensitive sodium chloride cotransporter abundance
      via DUSP6-mediated ERK1/2 signaling pathway.
AB  - Thiazide-sensitive sodium chloride cotransporter (NCC) plays an important role in
      maintaining blood pressure. Aldosterone is known to modulate NCC abundance.
      Previous studies reported that dietary salts modulated NCC abundance through
      either WNK4 [with no lysine (k) kinase 4]-SPAK (Ste20-related proline alanine
      rich kinase) or WNK4-extracellular signal-regulated kinase-1 and -2 (ERK1/2)
      signaling pathways. To exclude the influence of SPAK signaling pathway on the
      role of the aldosterone-mediated ERK1/2 pathway in NCC regulation, we
      investigated the effects of dietary salt changes and aldosterone on NCC abundance
      in SPAK knockout (KO) mice. We found that in SPAK KO mice low-salt diet
      significantly increased total NCC abundance while reducing ERK1/2
      phosphorylation, whereas high-salt diet decreased total NCC while increasing
      ERK1/2 phosphorylation. Importantly, exogenous aldosterone administration
      increased total NCC abundance in SPAK KO mice while increasing DUSP6 expression,
      an ERK1/2-specific phosphatase, and led to decreasing ERK1/2 phosphorylation
      without changing the ratio of phospho-T53-NCC/total NCC. In mouse distal
      convoluted tubule (mDCT) cells, aldosterone increased DUSP6 expression while
      reducing ERK1/2 phosphorylation. DUSP6 Knockdown increased ERK1/2 phosphorylation
      while reducing total NCC expression. Inhibition of DUSP6 by (E)-2-benzylidene-3
      (cyclohexylamino)-2,3-dihydro-1H-inden-1-one increased ERK1/2 phosphorylation and
      reversed the aldosterone-mediated increments of NCC partly by increasing NCC
      ubiquitination. Therefore, these data suggest that aldosterone modulates NCC
      abundance via altering NCC ubiquitination through a DUSP6-dependent ERK1/2 signal
      pathway in SPAK KO mice and part of the effects of dietary salt changes may be
      mediated by aldosterone in the DCTs. 

PMID- 25761882
TI  - Cholesterol affects flow-stimulated cyclooxygenase-2 expression and prostanoid
      secretion in the cortical collecting duct.
AB  - Essential hypertension (eHTN) is associated with hypercholesterolemia, but how
      cholesterol contributes to eHTN is unknown. Recent evidence demonstrates that
      short-term dietary cholesterol ingestion induces epithelial Na channel (ENaC)
      dependent Na absorption with a subsequent rise in blood pressure (BP),
      implicating cholesterol in salt-sensitive HTN. Prostaglandin E2 (PGE2), an
      autocrine/paracrine molecule, is induced by flow in endothelia to vasodilate the
      vasculature and inhibit ENaC-dependent Na absorption in the renal collecting duct
      (CD), which reduce BP. We hypothesize that cholesterol suppresses flow-mediated
      cyclooxygenase-2 (COX-2) expression and PGE2 release in the CD, which, in turn,
      affects Na absorption. Cortical CDs (CCDs) were microperfused at 0, 1, and 5
      nl.min(-1).mm(-1), and PGE2 release was measured. Secreted PGE2 was similar
      between no- and low-flow (151 +/- 28 vs. 121 +/- 48 pg.ml(-1).mm(-1)) CCDs, but
      PGE2 was greatest from high-flow (578 +/- 146 pg.ml(-1).mm(-1); P < 0.05) CCDs.
      Next, mice were fed either a 0 or 1% cholesterol diet, injected with saline to
      generate high urine flow rates, and CCDs were microdissected for PGE2 secretion.
      CCDs isolated from cholesterol-fed mice secreted less PGE2 and had a lower PGE2
      generating capacity than CCDs isolated from control mice, implying cholesterol
      repressed flow-induced PGE2 synthesis. Next, cholesterol extraction in a CD cell
      line induced COX-2 expression and PGE2 release while cholesterol incorporation,
      conversely, suppressed their expression. Moreover, fluid shear stress (FSS) and
      cholesterol extraction induced COX-2 protein abundance via p38-dependent
      activation. Thus cellular cholesterol composition affects biomechanical
      signaling, which, in turn, affects FSS-mediated COX-2 expression and PGE2 release
      via a p38-dependent mechanism. 

PMID- 25761883
TI  - Comparative assessment of genetic diversity among Indian bamboo genotypes using
      RAPD and ISSR markers.
AB  - Bamboo is one of the important plant for pulp, paper and charcoal industries.
      After China, India is the second largest bamboo reserve in Asia. Around the
      globe, wide genetic diversity of bamboo is present which serves as the base for
      selection and improvement. DNA based molecular markers appears to be a striking
      substitute for systematic assessment of the genetic diversity in conservation and
      genetic improvement of plants. DNA based molecular markers such as RAPD and ISSR
      were used to assess the genetic diversity in 13 bamboo genotypes. Total 120 RAPD
      and 63 ISSR primers were tested, of which only 42 polymorphic primers (30 RAPD
      and 12 ISSR), gave reproducible amplification profile and were used in this
      study. 30 RAPD primers yielded total 645 amplified fragments, of which 623 were
      polymorphic, and 20.76 polymorphic bands per primer were observed across 13
      genotypes. 12 ISSR primers produced 246 amplified fragments, of which 241 were
      polymorphic, and 20.08 polymorphic bands per primer was observed across 13
      different genotypes. The Jaccard's coefficient of RAPD, ISSR and pooled RAPD and
      ISSR dendrograms ranged from 0.26 to 0.83, 0.23 to 0.86 and 0.26 to 0.84
      respectively. The present study found the large genetic diversity present between
      different elite genotypes of bamboo. Such investigation can deliver a well
      understanding of the available genotypes, which might be further exploited for
      the paper industry. 

PMID- 25761885
TI  - Bilateral popliteal artery entrapment syndrome secondary to anomalous lateral
      heads of gastrocnemius.

PMID- 25761886
TI  - Cancer in global health: how do prevention and early detection strategies relate?
AB  - National cancer control plans are needed to stem the rapidly rising global cancer
      burden. Prevention and early detection are complementary but distinct strategies
      for cancer control. Some cancers are prevented through behavior and/or
      environmental modifications that reduce cancer risk, whereas other cancers are
      more amenable to treatment when they are successfully diagnosed at early stages.
      Prevention and early detection strategies should be prioritized on the basis of
      country-specific cancer demographics, modifiable risk factor distribution, and
      existing treatment resource availability. Following an individualized plan
      integrating prevention and early detection strategies, deficits can be targeted
      to strengthen national health systems for cancer control. 

PMID- 25761884
TI  - Combining Multiple Types of Motor Rehabilitation Enhances Skilled Forelimb Use
      Following Experimental Traumatic Brain Injury in Rats.
AB  - BACKGROUND: Neuroplasticity and neurorehabilitation have been extensively studied
      in animal models of stroke to guide clinical rehabilitation of stroke patients.
      Similar studies focused on traumatic brain injury (TBI) are lacking. OBJECTIVE:
      The current study was designed to examine the effects of individual and combined
      rehabilitative approaches, previously shown to be beneficial following stroke, in
      an animal model of moderate/severe TBI, the controlled cortical impact (CCI).
      METHODS: Rats received a unilateral CCI, followed by reach training, voluntary
      exercise, or unimpaired forelimb constraint, alone or in combination. Forelimb
      function was assessed at different time points post-CCI by tests of skilled
      reaching, motor coordination, and asymmetrical limb use. RESULTS: Following CCI,
      skilled reaching and motor coordination were significantly enhanced by
      combinations of rehabilitation strategies, not by individual approaches. The
      return of symmetrical limb use benefited from forelimb constraint alone. None of
      the rehabilitation strategies affected the size of injury, suggesting that
      enhanced behavioral function was not a result of neuroprotection. CONCLUSIONS:
      The current study has provided evidence that individual rehabilitation strategies
      shown to be beneficial in animal models of stroke are not similarly sufficient to
      enhance behavioral outcome in a model of TBI. Motor rehabilitation strategies for
      TBI patients may need to be more intense and varied. Future basic science studies
      exploring the underlying mechanisms of combined rehabilitation approaches in TBI
      as well as clinical studies comparing rehabilitation approaches for stroke versus
      TBI would prove fruitful.

PMID- 25761887
TI  - Stem cell hype: media portrayal of therapy translation.
AB  - In this Perspective, we examine the portrayal of translational stem cell research
      in major daily newspapers in Canada, the United States, and the United Kingdom
      between 2010 and 2013, focusing on how timelines for stem cell therapies were
      represented before and after Geron terminated its pioneering stem cell program.
      Our content analysis reveals that press coverage has shifted from ethical, legal,
      and social issues to clinical translation issues, and highly optimistic timelines
      were provided with no substantial change in representation over time. Scientists
      were the dominant voice with respect to translation timelines. The findings raise
      questions about the degree to which the media's overly optimistic slant fosters
      unrealistic expectations regarding the speed of clinical translation and
      highlight the ethical responsibility of stem cell researchers as public
      communicators. 

PMID- 25761889
TI  - Scanning ultrasound removes amyloid-beta and restores memory in an Alzheimer's
      disease mouse model.
AB  - Amyloid-beta (Abeta) peptide has been implicated in the pathogenesis of
      Alzheimer's disease (AD). We present a nonpharmacological approach for removing
      Abeta and restoring memory function in a mouse model of AD in which Abeta is
      deposited in the brain. We used repeated scanning ultrasound (SUS) treatments of
      the mouse brain to remove Abeta, without the need for any additional therapeutic
      agent such as anti-Abeta antibody. Spinning disk confocal microscopy and high
      resolution three-dimensional reconstruction revealed extensive internalization of
      Abeta into the lysosomes of activated microglia in mouse brains subjected to SUS,
      with no concomitant increase observed in the number of microglia. Plaque burden
      was reduced in SUS-treated AD mice compared to sham-treated animals, and cleared
      plaques were observed in 75% of SUS-treated mice. Treated AD mice also displayed
      improved performance on three memory tasks: the Y-maze, the novel object
      recognition test, and the active place avoidance task. Our findings suggest that
      repeated SUS is useful for removing Abeta in the mouse brain without causing
      overt damage, and should be explored further as a noninvasive method with
      therapeutic potential in AD. 

PMID- 25761888
TI  - Therapeutic exercise attenuates neutrophilic lung injury and skeletal muscle
      wasting.
AB  - Early mobilization of critically ill patients with the acute respiratory distress
      syndrome (ARDS) has emerged as a therapeutic strategy that improves patient
      outcomes, such as the duration of mechanical ventilation and muscle strength.
      Despite the apparent efficacy of early mobility programs, their use in clinical
      practice is limited outside of specialized centers and clinical trials. To
      evaluate the mechanisms underlying mobility therapy, we exercised acute lung
      injury (ALI) mice for 2 days after the instillation of lipopolysaccharides into
      their lungs. We found that a short duration of moderate intensity exercise in ALI
      mice attenuated muscle ring finger 1 (MuRF1)-mediated atrophy of the limb and
      respiratory muscles and improved limb muscle force generation. Exercise also
      limited the influx of neutrophils into the alveolar space through modulation of a
      coordinated systemic neutrophil chemokine response. Granulocyte colony
      stimulating factor (G-CSF) concentrations were systemically reduced by exercise
      in ALI mice, and in vivo blockade of the G-CSF receptor recapitulated the lung
      exercise phenotype in ALI mice. Additionally, plasma G-CSF concentrations in
      humans with acute respiratory failure (ARF) undergoing early mobility therapy
      showed greater decrements over time compared to control ARF patients. Together,
      these data provide a mechanism whereby early mobility therapy attenuates muscle
      wasting and limits ongoing alveolar neutrophilia through modulation of systemic
      neutrophil chemokines in lung-injured mice and humans. 

PMID- 25761890
TI  - Tumor cells, but not endothelial cells, mediate eradication of primary sarcomas
      by stereotactic body radiation therapy.
AB  - Cancer clinics currently use high-dose stereotactic body radiation therapy as a
      curative treatment for several kinds of cancers. However, the contribution of
      vascular endothelial cells to tumor response to radiation remains controversial.
      Using dual recombinase technology, we generated primary sarcomas in mice with
      targeted genetic mutations specifically in tumor cells or endothelial cells. We
      selectively mutated the proapoptotic gene Bax or the DNA damage response gene Atm
      to genetically manipulate the radiosensitivity of endothelial cells in primary
      soft tissue sarcomas. Bax deletion from endothelial cells did not affect
      radiation-induced cell death in tumor endothelial cells or sarcoma response to
      radiation therapy. Although Atm deletion increased endothelial cell death after
      radiation therapy, deletion of Atm from endothelial cells failed to enhance
      sarcoma eradication. In contrast, deletion of Atm from tumor cells increased
      sarcoma eradication by radiation therapy. These results demonstrate that tumor
      cells, rather than endothelial cells, are critical targets that regulate sarcoma
      eradication by radiation therapy. Treatment with BEZ235, a small-molecule protein
      kinase inhibitor, radiosensitized primary sarcomas more than the heart. These
      results suggest that inhibiting ATM kinase during radiation therapy is a viable
      strategy for radiosensitization of some tumors. 

PMID- 25761891
TI  - Virus-specific T lymphocytes home to the skin during natural dengue infection.
AB  - Dengue, which is the most prevalent mosquito-borne viral disease afflicting human
      populations, causes a spectrum of clinical symptoms that include fever, muscle
      and joint pain, maculopapular skin rash, and hemorrhagic manifestations. Patients
      infected with dengue develop a broad antigen-specific T lymphocyte response, but
      the phenotype and functional properties of these cells are only partially
      understood. We show that natural infection induces dengue-specific CD8(+) T
      lymphocytes that are highly activated and proliferating, exhibit antiviral
      effector functions, and express CXCR3, CCR5, and the skin-homing marker cutaneous
      lymphocyte-associated antigen (CLA). In the same patients, bystander human
      cytomegalovirus -specific CD8(+) T cells are also activated during acute dengue
      infection but do not express the same tissue-homing phenotype. We show that CLA
      expression by circulating dengue-specific CD4(+) and CD8(+) T cells correlates
      with their in vivo ability to traffic to the skin during dengue infection. The
      juxtaposition of dengue-specific T cells with virus-permissive cell types at
      sites of possible dengue exposure represents a previously uncharacterized form of
      immune surveillance for this virus. These findings suggest that vaccination
      strategies may need to induce dengue-specific T cells with similar homing
      properties to provide durable protection against dengue viruses. 

PMID- 25761892
TI  - The coronary substrate determines prognosis in acute coronary syndromes: the
      kaleidoscope has been shaken ... again!

PMID- 25761893
TI  - Duration of dual antiplatelet therapy after drug-eluting stent implantation: will
      we ever reach a consensus?

PMID- 25761894
TI  - The tyrosine kinase inhibitors imatinib and dasatinib reduce myeloid suppressor
      cells and release effector lymphocyte responses.
AB  - Immune escape mechanisms promote tumor progression and are hurdles of cancer
      immunotherapy. Removing immunosuppressive cells before treatment can enhance
      efficacy. Tyrosine kinase inhibitors (TKI) may be of interest to combine with
      immunotherapy, as it has been shown that the inhibitor sunitinib reduces myeloid
      suppressor cells in patients with renal cell carcinoma and dasatinib promotes
      expansion of natural killer-like lymphocytes in chronic myeloid leukemia (CML).
      In this study, the capacity of dasatinib and imatinib to reduce myeloid
      suppressor cells and to induce immunomodulation in vivo was investigated ex vivo.
      Samples from CML patients treated with imatinib (n = 18) or dasatinib (n = 14)
      within a Nordic clinical trial (clinicalTrials.gov identifier: NCT00852566) were
      investigated for the presence of CD11b(+)CD14(-)CD33(+) myeloid cells and
      inhibitory molecules (arginase I, myeloperoxidase, IL10) as well as the presence
      of natural killer cells, T cells (naive/memory), and stimulatory cytokines (IL12,
      IFNgamma, MIG, IP10). Both imatinib and dasatinib decreased the presence of
      CD11b(+)CD14(-)CD33(+) myeloid cells as well as the inhibitory molecules and the
      remaining myeloid suppressor cells had an increased CD40 expression. Monocytes
      also increased CD40 after therapy. Moreover, increased levels of CD40, IL12,
      natural killer cells, and experienced T cells were noted after TKI initiation.
      The presence of experienced T cells was correlated to a higher IFNgamma and MIG
      plasma concentration. Taken together, the results demonstrate that both imatinib
      and dasatinib tilted the immunosuppressive CML tumor milieu towards promoting
      immune stimulation. Hence, imatinib and dasatinib may be of interest to combine
      with cancer immunotherapy.

PMID- 25761896
TI  - An aqueous fluorescent probe for Hg(2+) detection with high selectivity and
      sensitivity.
AB  - An aqueous fluorescent probe, 1, was developed for the rapid detection of Hg(2+)
      with high sensitivity and excellent selectivity. Upon the addition of Hg(2+) in
      pure aqueous media, the Hg(2+)-mediated hydrolysis of vinyl ether and subsequent
      cyclization reactions converted probe 1 into the corresponding iminocoumarin dye,
      which is strongly fluorescent when excited. The application of this probe for the
      detection of intracellular Hg(2+) was successfully demonstrated in living cells.

PMID- 25761895
TI  - Enhancement of the proapoptotic properties of newcastle disease virus promotes
      tumor remission in syngeneic murine cancer models.
AB  - Newcastle disease virus (NDV) is considered a promising agent for cancer therapy
      due to its oncolytic properties. These include preferential replication in
      transformed cells, induction of innate and adaptive immune responses within
      tumors, and cytopathic effects in infected tumor cells due to the activation of
      apoptosis. To enhance the latter and thus possibly enhance the overall oncolytic
      activity of NDV, we generated a recombinant NDV encoding the human TNF receptor
      Fas (rNDV-B1/Fas). rNDV-B1/Fas replicates to similar titers as its wild-type
      (rNDV-B1) counterpart; however, overexpression of Fas in infected cells leads to
      higher levels of cytotoxicity correlated with faster and increased apoptosis
      responses, in which both the intrinsic and extrinsic pathways are activated
      earlier. Furthermore, in vivo studies in syngeneic murine melanoma models show an
      enhancement of the oncolytic properties of rNDV-B1/Fas, with major improvements
      in survival and tumor remission. Altogether, our data suggest that upregulation
      of the proapoptotic function of NDV is a viable approach to enhance its antitumor
      properties and adds to the currently known, rationally based strategies to design
      optimized therapeutic viral vectors for the treatment of cancer.

PMID- 25761897
TI  - In memoriam: B E Christopher Nordin.

PMID- 25761898
TI  - Youth suicide rate in rural US is nearly double that of urban areas, study finds.

PMID- 25761899
TI  - The transmembrane transporter domain of glutamate transporters is a process tip
      localizer.
AB  - Glutamate transporters in the central nervous system remove glutamate released
      from neurons to terminate the signal. These transporters localize to astrocyte
      process tips approaching neuronal synapses. The mechanisms underlying the
      localization of glutamate transporters to these processes, however, are not
      known. In this study, we demonstrate that the trimeric transmembrane transporter
      domain fragment of glutamate transporters, lacking both N- and C-terminal
      cytoplasmic regions, localized to filopodia tips. This is a common property of
      trimeric transporters including a neutral amino acid transporter ASCT1. Astrocyte
      specific proteins are not required for the filopodia tip localization. An
      extracellular loop at the centre of the 4(th) transmembrane helices, unique for
      metazoans, is required for the localization. Moreover, a C186S mutation at the
      4(th) transmembrane region of EAAT1, found in episodic ataxia patients,
      significantly decreased its process tip localization. The transmembrane
      transporter domain fragments of glutamate transporters also localized to
      astrocyte process tips in cultured hippocampal slice. These results indicate that
      the transmembrane transporter domain of glutamate transporters have an additional
      function as a sorting signal to process tips. 

PMID- 25761900
TI  - Single stream inertial focusing in a straight microchannel.
AB  - In the past two decades, microfluidics has become of great value in precisely
      aligning cells or microparticles within fluids. Microfluidic techniques use
      either external forces or sheath flow to focus particulate samples, and face the
      challenges of complex instrumentation design and limited throughput. The
      burgeoning field of inertial microfluidics brings single-position focusing
      functionality at throughput orders of magnitude higher than previously available.
      However, most inertial microfluidic focusers rely on cross-sectional flow-induced
      drag force to achieve single-position focusing, which inevitably complicates the
      device design and operation. In this work, we present an inertial microfluidic
      focuser that uses inertial lift force as the only driving force to focus
      microparticles into a single position. We demonstrate single-position focusing of
      different sized microbeads and cells with 95-100% efficiency, without the need
      for secondary flow, sheath flow or external forces. We further integrate this
      device with a laser counting system to form a sheathless flow cytometer, and
      demonstrated counting of microbeads with 2200 beads s(-1) throughput and 7%
      coefficient of variation. Cells can be completely recovered and remain viable
      after passing our integrated cytometry system. Our approach offers a number of
      benefits, including simplicity in fundamental principle and geometry, convenience
      in design, modification and integration, flexibility in focusing of different
      samples, high compatibility with real-world cellular samples as well as high
      precision and high-throughput single-position focusing. 

PMID- 25761902
TI  - Chemical modification of carbon nanomaterials (SWCNTs, DWCNTs, MWCNTs and SWCNHs)
      with diphenyl dichalcogenides.
AB  - Control over chemical functionalization is a crucial point in the field of
      nanotechnology. Herein, we present the covalent functionalization of several
      carbon nanoforms (single-walled carbon nanotubes, double-walled carbon nanotubes,
      multi-walled carbon nanotubes and carbon nanohorns) by means of diphenyl
      dichalcogenides. These ones show different reactivity to the nanomaterials and
      are able to modify their electronic properties depending on the electronegativity
      of the functionalizing heteroatom. Theoretical calculations were also performed
      to support the experimental results. All the modified structured nanocarbons were
      thoroughly characterized by TGA Raman, XPS, UV/Vis/nIR, IR and TEM techniques.
      Our findings propose a simple approach to functionalize carbon nanomaterials and,
      in the meantime, to tune their electronic properties. 

PMID- 25761901
TI  - Investigation of the conformational dynamics of the apo A2A adenosine receptor.
AB  - The activation/deactivation processes for G-protein coupled receptors (GPCRs)
      have been computationally studied for several different classes, including
      rhodopsin, the beta2 adrenergic receptor, and the M2 muscarinic receptor. Despite
      determined cocrystal structures of the adenosine A2A receptor (A2A AR) in complex
      with antagonists, agonists and an antibody, the deactivation process of this GPCR
      is not completely understood. In this study, we investigate the convergence of
      two apo simulations, one starting with an agonist-bound conformation (PDB:
      3QAK)(14) and the other starting with an antagonist-bound conformation (PDB:
      3EML)(11) . Despite the two simulations not completely converging, we were able
      to identify distinct intermediate steps of the deactivation process characterized
      by the movement of Y288(7.53) in the NPxxY motif. We find that Y288(7.53)
      contributes to the process by forming hydrogen bonds to residues in transmembrane
      helices 2 and 7 and losing these interactions upon full deactivation. Y197(5.58)
      also plays a role in the process by forming a hydrogen bond only once the side
      chain moves from the lipid interface to the middle of the helical bundle.

PMID- 25761903
TI  - Evidence for a common biological pathway linking three Parkinson's disease
      causing genes: parkin, PINK1 and DJ-1.
AB  - Parkinson's disease (PD) is characterised by the loss of dopaminergic neurons in
      the midbrain. Autosomal recessive, early-onset cases of PD are predominantly
      caused by mutations in the parkin, PINK1 and DJ-1 genes. Animal and cellular
      models have verified a direct link between parkin and PINK1, whereby PINK1
      phosphorylates and activates parkin at the outer mitochondrial membrane,
      resulting in removal of dysfunctional mitochondria via mitophagy. Despite the
      overwhelming evidence for this interaction, few studies have been able to
      identify a link for DJ-1 with parkin or PINK1. The aim of this review is to
      summarise the functions of these three proteins, and to analyse the existing
      evidence for direct and indirect interactions between them. DJ-1 is able to
      rescue the phenotype of PINK1-knockout Drosophila models, but not of parkin
      knockouts, suggesting that DJ-1 may act in a parallel pathway to that of the
      PINK1/parkin pathway. To further elucidate a commonality between these three
      proteins, bioinformatics analysis established that Miro (RHOT1) interacts with
      parkin and PINK1, and HSPA4 interacts with all three proteins. Furthermore, 30
      transcription factors were found to be common amongst all three proteins, with
      many of them being involved in transcriptional regulation. Interestingly,
      expression of these proteins and their associated transcription factors are found
      to be significantly down-regulated in PD patients compared to healthy controls.
      In summary, this review provides insight into common pathways linking three PD
      causing genes and highlights some key questions, the answers to which may provide
      critical insight into the disease process. 

PMID- 25761904
TI  - When an Intramolecular Disulfide Bridge Governs the Interaction of DUOX2 with Its
      Partner DUOXA2.
AB  - AIMS: The dual oxidase 2 (DUOX2) protein belongs to the NADPH oxidase (NOX)
      family. As H2O2 generator, it plays a key role in both thyroid hormone
      biosynthesis and innate immunity. DUOX2 forms with its maturation factor, DUOX
      activator 2 (DUOXA2), a stable complex at the cell surface that is crucial for
      the H2O2-generating activity, but the nature of their interaction is unknown. The
      contribution of some cysteine residues located in the N-terminal ectodomain of
      DUOX2 in a surface protein-protein interaction is suggested. We have investigated
      the involvement of different cysteine residues in the formation of covalent bonds
      that could be of critical importance for the function of the complex. RESULTS: We
      report the identification and the characterization of an intramolecular disulfide
      bond between cys-124 of the N-terminal ectodomain and cys-1162 of an
      extracellular loop of DUOX2, which has important functional implications in both
      export and activity of DUOX2. This intramolecular bridge provides structural
      support for the formation of interdisulfide bridges between the N-terminal domain
      of DUOX2 and the two extracellular loops of its partner, DUOXA2. INNOVATION: Both
      stability and function of the maturation factor, DUOXA2, are dependent on the
      oxidative folding of DUOX2, indicating that DUOX2 displays a chaperone-like
      function with respect to its partner. CONCLUSIONS: The oxidative folding of DUOX2
      that takes place in the endoplasmic reticulum (ER) appears to be a key event in
      the trafficking of the DUOX2/DUOXA2 complex as it promotes an appropriate
      conformation of the N-terminal region, which is propitious to subsequent covalent
      interactions with the maturation factor, DUOXA2.

PMID- 25761905
TI  - The endovascular approach for in-stent restenosis in femoropopliteal disease.
AB  - In-stent restenosis remains one of the main drawbacks of stenting the
      femoropopliteal segment, and leads to stent failure and repeated interventions. A
      variety of endovascular techniques have been investigated so far to reduce this
      phenomenon, including plain angioplasty, atherectomy, new stent deployment,
      cutting balloons and cryoplasty but without satisfactory mid- and long-term
      results. More recently drug-eluting devices have been applied in femoropopliteal
      in-stent restenosis with promising results. The aim of this review is to analyse
      the indication and effectiveness of those endovascular techniques for the
      treatment of in-stent restenosis.

PMID- 25761908
TI  - Synergy between polyaniline and OMt clay mineral in Langmuir-Blodgett films for
      the simultaneous detection of traces of metal ions.
AB  - We report on Langmuir-Blodgett (LB) films made with emeraldine salt polyaniline
      (PAni-ES) and organophilic montmorillonite clay mineral (OMt), where synergy
      between the components was reached to yield an enhanced performance in detecting
      trace levels of cadmium (Cd(2+)), lead (Pb(2+)) and copper (Cu(2+)). Detection
      was carried out using square wave anodic stripping (SWAS) voltammetry with indium
      tin oxide (ITO) electrodes modified with LB films of PAni-ES/OMt nanocomposite,
      whose data were compared to those obtained with electrodes coated with neat PAni
      ES and neat OMt LB films. The enhanced performance in the nanocomposite may be
      attributed to the stabilizing and ordering effect promoted by OMt in PAni-ES
      Langmuir films, which then led to more homogeneous LB films. According to X-ray
      diffraction data, the stacking of OMt layers was preserved in the LB films and
      therefore the PAni-ES chains did not cause clay mineral exfoliation. Instead, OMt
      affected the polaronic state of PAni-ES as indicated in UV-vis, Raman and FTIR
      spectra, also consistent with the changes observed for the Langmuir films. Taken
      together these results do indicate that semiconducting polymers and clay minerals
      may be combined for enhancing the electrical properties of nanostructures for
      sensing and related applications. 

PMID- 25761907
TI  - Mucolytic Agents Can Enhance HER2 Receptor Accessibility for [(89)Zr]Trastuzumab,
      Improving HER2 Imaging in a Mucin-Overexpressing Breast Cancer Xenograft Mouse
      Model.
AB  - PURPOSE: Binding of trastuzumab to HER2 receptors can be impaired by steric
      hindrance caused by mucin MUC4. As mucolytic drugs can breakdown disulfide bonds
      of mucoproteins, we checked if this approach could positively affect zirconium-89
      labeled trastuzumab ([(89)Zr]T) binding/uptake. PROCEDURES: The effect of N
      acetylcysteine (NAC) and MUC4 knockdown/stimulation on [(89)Zr]T binding/uptake
      were evaluated in MCF7(HER2-), BT474 and SKBr3(HER2+/MUC4-), and
      JIMT1(HER2+/MUC4+) cell lines. The results were then validated in SKBR3 and JIMT1
      tumor-bearing nude mice with a microPET-CT and ex vivo analysis. RESULTS:
      Significant increases in [(89)Zr]T binding/uptake were observed in JIMT1 cells
      following MUC4 knockdown (62.4 +/- 6.5%) and exposure to NAC (62.8 +/- 19.4%).
      Compared to controls, mice treated with NAC showed a significant increase in
      [(89)Zr]T uptake in MUC4 tumors on microPET-CT (SUVmean (18.3 +/- 4.7%), SUVmax
      (41.7 +/- 8.4%)) and individual organ counting (37.3 +/- 18.3%). In contrast, no
      significant differences were observed in SKBr3. CONCLUSION: NAC can enhance
      [(89)Zr]T accumulation and improve the HER2 imaging of MUC4-overexpressing
      tumors. The potential positive impact on trastuzumab-based treatment deserves
      further investigation.

PMID- 25761909
TI  - meso-Methylhydroxy BODIPY: a scaffold for photo-labile protecting groups.
AB  - Here, we show that by installing a meso-methylhydroxy moiety, the boron
      dipyrromethene (BODIPY) scaffold can be converted into an efficient caging group,
      removable by green light. We describe caging and uncaging of important chemical
      functionalities and demonstrate green light mediated control over biological
      processes in cultured cell lines and neurons. 

PMID- 25761906
TI  - The Therapeutic Effects of Human Mesenchymal Stem Cells Primed with Sphingosine-1
      Phosphate on Pulmonary Artery Hypertension.
AB  - Stem cell (SC) therapy has become a potential treatment modality for pulmonary
      artery hypertension (PAH), but the efficacy of human SC and priming effects have
      not yet been established. The mobilization and homing of hematopoietic stem cells
      (HSCs) are modulated by priming factors that include a bioactive lipid,
      sphingosine-1-phosphate (S1P), which stimulates CXCR4 receptor kinase signaling.
      Here, we show that priming human mesenchymal stem cells (MSCs) with S1P enhances
      their therapeutic efficacy in PAH. Human MSCs, similar to HSCs, showed stronger
      chemoattraction to S1P in transwell assays. Concomitantly, MSCs treated with 0.2
      MUM S1P showed increased phosphorylation of both MAPKp42/44 and AKT protein
      compared with nonprimed MSCs. Furthermore, S1P-primed MSCs potentiated colony
      forming unit-fibroblast, anti-inflammatory, and angiogenic activities of MSCs in
      culture. In a PAH animal model induced by subcutaneously injected monocrotaline,
      administration of human cord blood-derived MSCs (hCB-MSCs) or S1P-primed cells
      significantly attenuated the elevated right ventricular systolic pressure.
      Notably, S1P-primed CB-MSCs, but not unprimed hCB-MSCs, also elicited a
      significant reduction in the right ventricular weight ratio and pulmonary
      vascular wall thickness. S1P-primed MSCs enhanced the expression of several genes
      responsible for stem cell trafficking and angiogenesis, increasing the density of
      blood vessels in the damaged lungs. Thus, this study demonstrates that human MSCs
      have potential utility for the treatment of PAH, and that S1P priming increases
      the effects of SC therapy by enhancing cardiac and vascular remodeling. By
      optimizing this protocol in future studies, SC therapy might form a basis for
      clinical trials to treat human PAH. 

PMID- 25761910
TI  - Nondestructive tribochemistry-assisted nanofabrication on GaAs surface.
AB  - A tribochemistry-assisted method has been developed for nondestructive surface
      nanofabrication on GaAs. Without any applied electric field and post etching,
      hollow nanostructures can be directly fabricated on GaAs surfaces by sliding a
      SiO2 microsphere under an ultralow contact pressure in humid air. TEM observation
      on the cross-section of the fabricated area shows that there is no appreciable
      plastic deformation under a 4 nm groove, confirming that GaAs can be removed
      without destruction. Further analysis suggests that the fabrication relies on the
      tribochemistry with the participation of vapor in humid air. It is proposed that
      the formation and breakage of GaAs-O-Si bonding bridges are responsible for the
      removal of GaAs material during the sliding process. As a nondestructive and
      conductivity-independent method, it will open up new opportunities to fabricate
      defect-free and well-ordered nucleation positions for quantum dots on GaAs
      surfaces.

PMID- 25761911
TI  - [Benign course of diffuse cutaneous mastocytosis with massive blisters].
AB  - BACKGROUND: Diffuse cutaneous mastocytosis is a rare disease with increased
      numbers of mast cells and development of blisters, which can be easily
      overlooked. CASE REPORT: A 6-month-old girl was presented by her parents with
      acute onset of numerous, disseminated bullae on her body. Histology revealed
      numerous mast cells in a skin sample and highly elevated serum tryptase levels
      were detected. The diagnosis of diffuse cutaneous mastocytosis was made. The
      patient was medically treated with glucocorticoids and antibiotics. Within a few
      years of time a complete remission of developing bullae, a major clinical
      improvement as well as a continuous decrease of basal tryptase was seen. Today,
      the girl is 14 years old and without any apparent limitation due to the disease
      and in fact she is very successful in competitive sports. CONCLUSION: Despite
      often severe symptoms at first manifestation, this clinical development showing a
      benign course is typical in children.

PMID- 25761912
TI  - Selective ingress of a Samoan plume component into the northern Lau backarc
      basin.
AB  - Intra-plate basalt isotopic trends require mixing between enriched mantle
      components (EM1, EM2, HIMU) and a primordial component with high (3)He/(4)He
      termed FOZO. However, proportions of components, geometric distributions within
      individual plumes, relative proportions of melting components and loci of mixing
      of melts and residues remain poorly understood. Here we present new Hf-Nd
      isotopic data of dredged sea floor basalts from the northern Lau backarc basin,
      ~250 km south of the subaerial and submerged Samoan chain, with high (3)He/(4)He,
      (20)Ne/(22)Ne and primordial (129)Xe/(130)Xe, characteristic of the FOZO
      component. Combined Hf-Nd-noble gas isotope systematics require mixing of
      refractory, sub-northwestern Lau backarc mantle only with a spatially restricted
      FOZO component, most plausibly sourced from part of the Samoan plume. Other
      geographically restricted and possibly volumetrically minor enriched Samoan plume
      components are not detectable in northern Lau backarc samples, consistent with
      selective plume ingress of the FOZO component beneath the basin. 

PMID- 25761913
TI  - The use of an automated notification system to identify and address early
      readmissions by a university hospitalist service.
AB  - OBJECTIVES: To examine the association of an automated physician feedback system
      prompting physician review of early readmissions with a change in overall
      readmission rates. METHODS: The University of Utah Internal Medicine Hospitalist
      Service created an automated system to alert discharging providers to any patient
      readmitted within 30 days. For any 7-day readmission, the physician was asked to
      complete a survey to describe the admission and discharge and to identify
      contributing factors to the readmission. Using the University HealthSystem
      Consortium database, readmission rates were compared prior to and following this
      intervention. RESULTS: Following the intervention, 30-day readmission rates
      significantly decreased from 13.93% to 11.99% (p = 0.0298). The 7-day readmission
      rates decreased as well but the findings were not statistically significant. The
      discharging physician deemed 45% of the readmissions preventable or probably
      preventable. CONCLUSION: Readmissions are common, costly and potentially
      preventable. This tool for physician audit and feedback and identification of
      defects contributing to readmissions was associated with a statistically
      significant decrease in 30-day readmissions. Further investigation is needed to
      verify these results and evaluate the best mechanism of application.

PMID- 25761916
TI  - Translation of a Ski School Sun Safety Program to North American Ski and
      Snowboard Schools.
AB  - Health promotion programs that develop and implement strategies to promote sun
      safety practices to children have the potential to reduce skin cancer occurrence
      later in life. Go Sun Smart (GSS), a sun safety program for employees and guests
      of ski areas, was distributed to determine if an enhanced dissemination strategy
      was more effective than a basic dissemination strategy at reaching parents at ski
      and snowboard schools. On-site observations of GSS use and surveys of 909
      parents/caregivers with children enrolled in ski and snowboard schools at 63 ski
      areas were conducted and analyzed using techniques for clustered designs. No
      differences were identified by dissemination strategy. Greater implementation of
      GSS (>5 messages posted) was associated with greater parental recall, 36.6%
      versus 16.7%, of materials, but not greater sun protection practices. Greater
      recall of messages, regardless of level of implementation, resulted in greater
      sun protection practices including applying sunscreen (p < .05), providing
      sunglasses and goggles (p < .01), and more use of all sun protection practices (p
      < .01). Ski areas with more program materials appeared to reach parents with sun
      safety advice and thus convinced them to take more precautions for their
      children. Sun safety need not be at odds with children's outdoor recreation
      activities. 

PMID- 25761917
TI  - Antifungal properties of peptidomimetics with an arginine-[beta-(2,5,7-tri-tert
      butylindol-3-yl)alanine]-arginine motif against Saccharomyces cerevisiae and
      Zygosaccharomyces bailii.
AB  - Due to increased occurrence of infections and food spoilage caused by yeast,
      there is an unmet need for new antifungal agents. The arginine-beta-(2,5,7-tri
      tert-butylindol-3-yl) alanine-arginine (R-Tbt-R) motif was previously proved
      useful in the design of an antifungal tripeptide. Here, an array of
      peptidomimetics based on this motif was investigated for antifungal and hemolytic
      activity. The five most promising modified tetrapeptide analogues ( 6: and 9-12:
      contain an additional C-terminal hydrophobic residue, and these were found to
      exhibit antifungal activity against Saccharomyces cerevisiae (MIC 6 and 12 MUg
      mL(-1)) and Zygosaccharomyces bailii (MIC 6-25 MUg mL(-1)). Four compounds ( 6:
      and 9-11: , had limited hemolytic activity (<10% hemolysis at 8 * MIC).
      Determination of their killing kinetics revealed that compound 9: displayed
      fungicidal effect. Testing against cells from an S. cerevisiae deletion mutant
      library indicated that interaction with yeast-specific fungal sphingolipids, most
      likely constitutes a crucial step in the mode of action. Interestingly, a lack of
      activity of peptidomimetics 6: and 9-11: towards Candida spp. was shown to be due
      to degradation or sequestering by the yeast. Due to their ultrashort nature,
      antifungal activity and low toxicity, the four compounds may have potential as
      leads for novel preservatives.

PMID- 25761914
TI  - Prefrontal cortex and the dysconnectivity hypothesis of schizophrenia.
AB  - Schizophrenia is hypothesized to arise from disrupted brain connectivity. This
      "dysconnectivity hypothesis" has generated interest in discovering whether there
      is anatomical and functional dysconnectivity between the prefrontal cortex (PFC)
      and other brain regions, and how this dysconnectivity is linked to the impaired
      cognitive functions and aberrant behaviors of schizophrenia. Critical advances in
      neuroimaging technologies, including diffusion tensor imaging (DTI) and
      functional magnetic resonance imaging (fMRI), make it possible to explore these
      issues. DTI affords the possibility to explore anatomical connectivity in the
      human brain in vivo and fMRI can be used to make inferences about functional
      connections between brain regions. In this review, we present major advances in
      the understanding of PFC anatomical and functional dysconnectivity and their
      implications in schizophrenia. We then briefly discuss future prospects that need
      to be explored in order to move beyond simple mapping of connectivity changes to
      elucidate the neuronal mechanisms underlying schizophrenia. 

PMID- 25761918
TI  - Chrono-proteomics of human saliva: variations of the salivary proteome during
      human development.
AB  - An important contribution to the variability of any proteome is given by the time
      dimension that should be carefully considered to define physiological
      modifications. To this purpose, whole saliva proteome was investigated in a wide
      age range. Whole saliva was collected from 17 preterm newborns with a
      postconceptional age at birth of 178-217 days. In these subjects sample
      collection was performed serially starting immediately after birth and within
      about 1 year follow-up, gathering a total of 111 specimens. Furthermore, whole
      saliva was collected from 182 subjects aged between 0 and 17 years and from 23
      adults aged between 27 and 57 years. The naturally occurring intact salivary
      proteome of the 316 samples was analyzed by low- and high-resolution HPLC-ESI-MS
      platforms. Proteins peculiar of the adults appeared in saliva with different time
      courses during human development. Acidic proline-rich proteins encoded by PRH2
      locus and glycosylated basic proline-rich proteins encoded by PRB3 locus appeared
      following 180 days of postconceptional age, followed at 7 months (+/-2 weeks) by
      histatin 1, statherin, and P-B peptide. The other histatins and acidic proline
      rich proteins encoded by PRH1 locus appeared in whole saliva of babies from 1 to
      3 weeks after the normal term of delivery, S-type cystatins appeared at 1 year
      (+/-3 months), and basic proline-rich proteins appeared at 4 years (+/-1 year) of
      age. All of the proteinases involved in the maturation of salivary proteins were
      more active in preterm than in at-term newborns, on the basis of the truncated
      forms detected. The activity of the Fam20C kinase, involved in the
      phosphorylation of various proteins, started around 180 days of postconceptional
      age, slowly increased reaching values comparable to adults at about 2 years (+/-6
      months) of age. Instead, MAPK14 involved in the phosphorylation of S100A9 was
      fully active since birth also in preterm newborns. 

PMID- 25761919
TI  - Oribatid mite communities along an elevational gradient in Sairme gorge
      (Caucasus).
AB  - Many aboveground animals and plant communities have been studied along
      elevational gradients whereas studies on soil animals are scarce. Here, we
      studied oribatid mite community distribution along an elevational gradient from
      600 to 2200 m in forest ecosystems of the Western Lesser Caucasus Mountains in
      Georgia. Overall, 86 oribatid mite species were found at the study sites.
      Oribatid mite densities were generally low (~9800 ind./m(2)), and 74% of all
      species reproduced sexually indicating that resource conditions at the study
      sites are generally poor. Oribatids mainly comprised Brachypylina (76%),
      Mixonomata (13%), Desmonomata (6%) and Enarthronota (5%). Oribatid mite community
      structure changed along the elevational gradient and the changes correlated with
      temperature, pH, litter thickness and density of the herb layer. The dominance of
      sexually reproducing taxa and low overall abundance indicate that the studied
      elevational gradient is characterized by poor resource conditions for soil
      microarthropods. Oribatid mite species richness and density declined with
      elevation suggesting that decreasing temperature in concert with resource
      limitation is a main driver of oribatid mite communities whereas stochastic
      factors (such as mid-domain effects) are of minor importance.

PMID- 25761920
TI  - The role of expectation in the therapeutic outcomes of alcohol and drug addiction
      treatments.
AB  - Throughout history, patient-physician relationships have been acknowledged as an
      important component of the therapeutic effects of any pharmacological treatment.
      Here, we discuss the role of physicians' expectations in influencing the
      therapeutic outcomes of alcohol and drug addiction pharmacological treatments. As
      largely demonstrated, such expectations and attitudes may contribute to produce
      placebo and nocebo effects that in turn affect the course of the disease and the
      response to the therapy. This article is aimed at discussing the current insights
      into expectations, placebo and nocebo mechanisms and their impact on the
      therapeutic outcomes of alcohol and drug addiction treatments; with the goal of
      informing physicians and other health care providers about the potentially
      widespread implications for clinical practice and for a successful treatment
      regimen.

PMID- 25761921
TI  - Evaluation of hot-melt extrusion and injection molding for continuous
      manufacturing of immediate-release tablets.
AB  - The exploitation of hot-melt extrusion and injection molding for the
      manufacturing of immediate-release (IR) tablets was preliminarily investigated in
      view of their special suitability for continuous manufacturing, which represents
      a current goal of pharmaceutical production because of its possible advantages in
      terms of improved sustainability. Tablet-forming agents were initially screened
      based on processability by single-screw extruder and micromolding machine as well
      as disintegration/dissolution behavior of extruded/molded prototypes. Various
      polymers, such as low-viscosity hydroxypropylcellulose, polyvinyl alcohol,
      polyvinyl alcohol-polyethylene glycol graft copolymer, various sodium starch
      glycolate grades (e.g., Explotab((r)) CLV) that could be processed with no need
      for technological aids, except for a plasticizer, were identified. Furthermore,
      the feasibility of both extruded and molded IR tablets from low-viscosity
      hydroxypropylcellulose or Explotab((r)) CLV was assessed. Explotab((r)) CLV, in
      particular, showed thermoplastic properties and a very good aptitude as a tablet
      forming agent, starting from which disintegrating tablets were successfully
      obtained by either techniques. Prototypes containing a poorly soluble model drug
      (furosemide), based on both a simple formulation (Explotab((r)) CLV and
      water/glycerol as plasticizers) and formulations including
      dissolution/disintegration adjuvants (soluble and effervescent excipients) were
      shown to fulfill the USP 37 dissolution requirements for furosemide tablets.

PMID- 25761922
TI  - Response to 'the role of macroaggregated albumin lung perfusion scan in
      hepatopulmonary syndrome: are we ready to draw conclusions?'.

PMID- 25761923
TI  - The journey of antiphospholipid antibodies from cellular activation to
      antiphospholipid syndrome.
AB  - Pathogenic antiphospholipid antibodies (aPL) are the driving factors of recurrent
      pregnancy loss and thrombosis that characterize antiphospholipid syndrome (APS).
      Current evidence indicates that aPL induce a procoagulant phenotype in the
      vasculature and abnormal cellular proliferation and differentiation in placental
      tissues to cause the typical clinical features; however, the molecular mechanisms
      underlying these processes remain incompletely understood. Inflammation serves as
      a necessary link between the observed procoagulant phenotype and actual thrombus
      development and is an important mediator of the placental injury in APS patients.
      However, the underlying mechanisms for these events have also not been fully
      elucidated. In this review, we will outline the available data that give us our
      current understanding of the pathophysiology of APS, especially as it relates to
      the development of thromboembolic and obstetric pathological phenomena in these
      patients. We will also describe the intracellular signaling pathways activated by
      aPL in various cellular subtypes and outline the current evidence linking these
      pathways to clinical phenotypes. Finally, we will discuss the implications of
      distinct molecular patterns defining clinical phenotypes of APS patients. 

PMID- 25761925
TI  - Update on juvenile systemic sclerosis.
AB  - Juvenile systemic sclerosis is an orphan disease of the macro- and
      microvasculature with an unknown etiology. Although pediatric and adult
      classification systems have been developed, neither has been validated yet.
      Recent publications have shown a shift in the subset pattern in juvenile-onset
      adult patients, with a better outcome in these patients as compared with young
      adult patients. As a first step in assessing activity, damage, and severity, a
      pediatric severity score--a modification of the adult Medsger scale--was proposed
      but has not been validated. An activity score also has been developed but has not
      yet been published. Currently, treatment approaches are based only on adult data,
      and problems exist in extrapolating these data to a pediatric population.

PMID- 25761924
TI  - Reviewing the recommendations for lupus in children.
AB  - Systemic lupus erythematosus (SLE) is an autoimmune connective tissue disorder
      with severe morbidity and mortality and diverse systemic involvement. Disease
      onset occurs during childhood in approximately 15 % of patients with SLE. It is
      important to treat the attacks adequately and prevent further flares for
      favorable long-term outcomes. The aim of effective disease management with early
      immunosuppression is to achieve symptomatic resolution and improvement in the
      quality of life by maintaining sustained remission and thereby preventing tissue
      damage. Adult literature on SLE management has evolved considerably over the past
      few decades based on observations from clinical studies investigating different
      immunosuppressive agents. We lack well-designed randomized controlled trials in
      children with SLE, thus we mainly depend on adult literature. Here, we review the
      literature for the current management of SLE in children and we present the
      recommendations and suggestions with the level of evidence. 

PMID- 25761927
TI  - Imaging of calcium pyrophosphate deposition disease.
AB  - Calcium pyrophosphate deposition disease (CPPD) is a common and clinically
      heterogeneous form of arthritis caused by the deposition of calcium pyrophosphate
      (CPP) crystals in articular tissues. The diagnosis of CPPD is supported by the
      presence of radiographic chondrocalcinosis; yet, conventional radiography detects
      only about 40 % of clinically important CPPD. Here, we critically review the
      recent literature on imaging in CPPD. New studies inform our use of conventional
      radiographic screening methodologies for CPPD and provide additional evidence for
      the utility of diagnostic ultrasound. Recent work also highlights the
      polyarticular nature of CPPD, its association with tissue damage, and the high
      prevalence of tendon involvement. While dual energy CT and diffraction-enhanced
      synchrotron imaging remain research tools, they present potential avenues for
      improved visualization of CPP deposits. Advances in imaging in CPPD will increase
      diagnostic accuracy and eventually result in better management of this common
      form of arthritis. 

PMID- 25761926
TI  - The gouty tophus: a review.
AB  - The tophus is the cardinal feature of advanced gout. This review summarises
      recent research into the biology, impact and treatment of tophaceous gout.
      Microscopically, tophi are chronic foreign body granuloma-like structures
      containing collections of monosodium urate (MSU) crystals surrounded by
      inflammatory cells and connective tissue. Extracellular trap formation mediated
      by neutrophil interactions with MSU crystals may be a central checkpoint in
      tophus formation. Gouty tophi impact on many aspects of health-related quality of
      life. Tophi are also implicated in the development of structural joint damage and
      increased mortality risk in people with gout. Effective treatment of tophaceous
      gout requires long-term urate-lowering therapy, ideally to achieve a serum urate
      concentration of <5 mg/dL (300 MUmol/L). Recent advances in gout therapeutics
      have expanded urate-lowering therapy options for patients with severe tophaceous
      disease to allow faster regression of tophi, improved health-related quality of
      life and, potentially, improved structural outcomes. 

PMID- 25761929
TI  - Comparison of human expert and computer-automated systems using magnitude-squared
      coherence (MSC) and bootstrap distribution statistics for the interpretation of
      pattern electroretinograms (PERGs) in infants with optic nerve hypoplasia (ONH).
AB  - PURPOSE: Pattern electroretinograms (PERGs) have inherently low signal-to-noise
      ratios and can be difficult to detect when degraded by pathology or noise. We
      compare an objective system for automated PERG analysis with expert human
      interpretation in children with optic nerve hypoplasia (ONH) with PERGs ranging
      from clear to undetectable. METHODS: PERGs were recorded uniocularly with chloral
      hydrate sedation in children with ONH (aged 3.5-35 months). Stimuli were
      reversing checks of four sizes focused using an optical system incorporating the
      cycloplegic refraction. Forty PERG records were analysed; 20 selected at random
      and 20 from eyes with good vision (fellow eyes or eyes with mild ONH) from over
      300 records. Two experts identified P50 and N95 of the PERGs after manually
      deleting trials with movement artefact, slow-wave EEG (4-8 Hz) or other noise
      from raw data for 150 check reversals. The automated system first identified
      present/not-present responses using a magnitude-squared coherence criterion and
      then, for responses confirmed as present, estimated the P50 and N95 cardinal
      positions as the turning points in local third-order polynomials fitted in the -3
      dB bandwidth [0.25 ... 45] Hz. Confidence limits were estimated from bootstrap re
      sampling with replacement. The automated system uses an interactive Internet
      available webpage tool (see http://clinengnhs.liv.ac.uk/esp_perg_1.htm). RESULTS:
      The automated system detected 28 PERG signals above the noise level (p <= 0.05
      for H0). Good subjective quality ratings were indicative of significant PERGs;
      however, poor subjective quality did not necessarily predict non-significant
      signals. P50 and N95 implicit times showed good agreement between the two experts
      and between experts and the automated system. For the N95 amplitude measured to
      P50, the experts differed by an average of 13% consistent with differing
      interpretations of peaks within noise, while the automated amplitude measure was
      highly correlated with the expert measures but was proportionally larger. Trial
      by-trial review of these data required approximately 6.5 h for each human expert,
      while automated data processing required <4 min, excluding overheads relating to
      data transfer. CONCLUSIONS: An automated computer system for PERG analysis, using
      a panel of signal processing and statistical techniques, provides objective
      present/not-present detection and cursor positioning with explicit confidence
      intervals. The system achieves, within an efficient and robust statistical
      framework, estimates of P50 and N95 amplitudes and implicit times similar to
      those of clinical experts.

PMID- 25761928
TI  - Vigabatrin can enhance electroretinographic responses in pigmented and albino
      rats.
AB  - PURPOSE: To evaluate the effects of the antiepileptic medication vigabatrin (VGB)
      on the retina of pigmented rats. METHODS: Scotopic and photopic
      electroretinograms were recorded from dark- and light-adapted Long-Evans
      (pigmented) and Sprague Dawley (albino) rats administered, daily, 52-55
      injections of 250 mg.kg(-1).day(-1) VGB or 25-26 injections of 500 mg.kg(-1).day(
      1) VGB, or a corresponding number of sham injections. Sensitivity and saturated
      amplitude of the rod photoresponse (S, Rm(P3)) and postreceptor response
      (1/sigma, Vm) were derived, as were sensitivity and amplitude of the cone
      mediated postreceptor response (1/sigma(cone), Vm(cone)). The oscillatory
      potentials and responses to a series of flickering lights (6.25, 12.5, 25 and 50
      Hz) were studied in the time and frequency domains. A subset of rats' eyes was
      harvested for Western blotting or histology. RESULTS: Of the parameters derived
      from dark-adapted ERG responses, in both pigmented and albino rats, VGB
      repeatedly and reliably enhanced electroretinographic parameters; no significant
      ERG deficits were noted. No significant alterations were observed in ER/oxidative
      stress or in the Akt cell death/survival pathway. There were migrations of
      photoreceptor nuclei toward the RPE and outgrowths of bipolar cell dendrites into
      the outer nuclear layer in VGB-treated rats; these were never observed in sham
      treated animals. CONCLUSIONS: Although VGB is associated with retinal dysfunction
      in patients and VGB toxicity has been demonstrated by other laboratories in the
      albino rat, in our pigmented and albino rats, VGB did not induce deficits in, but
      rather enhanced, retinal function. Nonetheless, retinal neuronal dysplasia was
      observed.

PMID- 25761930
TI  - The hippocampal to prefrontal cortex circuit in mice: a promising
      electrophysiological signature in models for psychiatric disorders.
AB  - Interaction between the hippocampus and the medial prefrontal cortex (mPFC) has
      been identified as a key target in several neuropsychiatric disorders. However,
      the hippocampus-mPFC (H-PFC) pathway has not been outlined in mice, which are
      increasingly the leading choice for new animal models for neurological disorders.
      Our results, establish the existence of a topographical, monosynaptic pathway
      originating exclusively from the ventral CA1 and subiculum to the mPFC.
      Functional connectivity of the H-PFC pathway, examined in vivo through field
      potential recordings in the prelimbic mPFC after high-frequency stimulation of
      the hippocampal outflow, demonstrates an induction of a significant long lasting
      long-term potentiation, which is stable for at least one hour and strongly
      impaired by exposure to acute stress. Given that stress exposure is known to have
      serious detrimental effects on prefrontal cortical functioning and is considered
      a major risk factor for several neuropsychiatric disorders, the present study
      provides a crucial animal model of neural interaction and response to
      environmental stress which could lend itself to the study of disruption of brain
      circuits and test for potential drug candidates.

PMID- 25761931
TI  - Novel subventricular zone early progenitor cell-specific adenovirus for in vivo
      therapy of central nervous system disorders reinforces brain stem cell
      heterogeneity.
AB  - Neural stem/progenitor cells (NSPCs) have the potential to self-renew and to
      generate all neural lineages as well as to repopulate damaged areas in the brain.
      Our previous targeting strategies have indicated precursor cell heterogeneity
      between different brain regions that warrants the development of NSPC-specific
      delivery vehicles. Here, we demonstrate a target-specific adenoviral vector
      system for the in vivo manipulation of progenitor cells in the subventricular
      zone of the adult mouse brain. For this purpose, we identified a series of
      peptide ligands via phage display. The peptide with the highest affinity,
      SNQLPQQ, was expressed in conjunction with a bispecific adaptor molecule. To
      verify the targeting potential of the specific peptide, green fluorescent protein
      expressing Ad vectors were coupled with the adaptor molecule and injected into
      the subventricular region of adult mice by stereotaxic surgery. An efficient and
      selective transduction of NSPCs in the SVZ was achieved, whereas hippocampal
      NSPCs were negative. Our results offer an expeditious and simple tool to produce
      retargeted viral vectors for a specific and direct in vivo manipulation of these
      progenitor cells. This powerful technique provides an opportunity to develop
      innovative strategies and express therapeutic genes in specific types of neural
      progenitor cells to allow success in treatment of brain disorders.

PMID- 25761932
TI  - Differential Cardiac MicroRNA Expression Predicts the Clinical Course in Human
      Enterovirus Cardiomyopathy.
AB  - BACKGROUND: Investigation of disease pathogenesis confined to protein-coding
      regions of the genome may be incomplete because many noncoding variants are
      associated with disease. We aimed to identify novel predictive markers for the
      course of enterovirus (CVB3) cardiomyopathy by screening for noncoding elements
      influencing the grossly different antiviral capacity of individual patients.
      METHODS AND RESULTS: Transcriptome mapping of CVB3 cardiomyopathy patients
      revealed distinctive cardiac microRNA (miR) patterns associated with spontaneous
      virus clearance and recovery (CVB3-ELIM) versus virus persistence and progressive
      clinical deterioration (CVB3-PERS). Profiling of protein-coding genes and 754
      miRs in endomyocardial biopsies of test cohorts was performed at their initial
      presentation, and those spontaneously eliminating the virus were compared with
      those with virus persistence on follow-up. miR profiling revealed highly
      significant differences in cardiac levels of 16 miRs, but not of protein-coding
      genes. Evaluation of this primary distinctive miR pattern in validation cohorts,
      and multivariate receiver operating characteristic curve analysis, confirmed this
      pattern as highly predictive for disease course (area under the curve, 0.897+/
      0.071; 95% confidence interval, 0.758-1.000). Eight miRs were strongly induced in
      CVB3-PERS (miRs 135b, 155, 190, 422a, 489, 590, 601, 1290), but undetectable in
      CVB3-ELIM or controls. They are predicted to target multiple immune response
      genes, and 2 of these were confirmed by antisense-mediated ablation of miRs 135b,
      190, and 422a in the monocytic THP-1 cell line. CONCLUSIONS: An immediate
      clinical application of the data is cardiac miR profiling to assess the risk of
      virus persistence and progressive clinical deterioration in CVB3 cardiomyopathy.
      Patients at risk are eligible for immediate antiviral therapy to minimize
      irreversible cardiac damage.

PMID- 25761933
TI  - Common molecular etiology of nonsyndromic hearing loss in 484 patients of 3
      ethnicities in northwest China.
AB  - CONCLUSIONS: In the study population in northwest China, a total of 33.06% of
      deaf patients have inherited hearing impairment caused by GJB2, SLC26A4, and
      mtDNA 1555A>G mutations. The mutation frequencies of GJB2, SLC26A4, and mtDNA
      1555A>G genes were 16.12%, 10.54%, and 6.4%, respectively, in our study cohort.
      Thus, screening is conventionally performed for GJB2, SLC26A4, and mtDNA 1555A>G
      in these populations. OBJECTIVE: This study aimed to investigate the mutations of
      GJB2, mitochondrial DNA 12S rRNA1555A>G, and SLC26A4 genes in Han Chinese, Hui
      people, and Tibetan ethnicities in patients with nonsyndromic hearing loss (NSHL)
      in northwest China. METHODS: A total of 484 unrelated subjects with hearing loss
      who attended special education schools in northwest China were enrolled in this
      study. Three prominent deafness-related genes, GJB2, SLC26A4, and mtDNA 1555A>G,
      were screened for mutations in our study cohort. RESULTS: The mutation
      frequencies of GJB2, SLC26A4, and mtDNA 1555A>G genes were 16.12%, 10.54%, and
      6.4%, respectively. The prevalence of GJB2 mutations was 17.52%, 15.35%, and
      11.43% in Han Chinese, Hui people, and Tibetan participants, respectively.
      c.235delC was the most prevalent mutation, accounting for 65.71% of all GJB2
      mutant alleles. The prevalence of SLC26A4 mutations was 12.39%, 8.84%, and 8.57%
      in Han Chinese, Hui people, and Tibetan participants, respectively. The c.919-2
      A>G mutation was the most common form, accounting for 60.47% of all SLC26A4
      mutant alleles. The prevalence of the homoplasmic mtDNA 1555A>G mutation was
      8.97%, 3.72%, and 5.71% in Han Chinese, Hui people, and Tibetan participants,
      respectively, which represents a statistically significant difference between the
      Han Chinese and Hui people (chi(2) = 5.118, p < 0.05).

PMID- 25761934
TI  - F604S exchange in FIP1L1-PDGFRA enhances FIP1L1-PDGFRA protein stability via SHP
      2 and SRC: a novel mode of kinase inhibitor resistance.
AB  - FIP1L1-PDGFRA is a constitutively activated kinase described in chronic
      eosinophilic leukemia (CEL) and hypereosinophilic syndrome (HES). Imatinib is
      clinically active in FIP1L1-PDGFRA-positive diseases. Using in vitro screening to
      identify imatinib-resistant mutations, we frequently detected a Phe to Ser
      exchange at position 604 (F604S) of FIP1L1-PDGFRA alone or in combination with
      other exchanges. Surprisingly, FIP1L1-PDGFRA/F604S did not increase the
      biochemical or cellular IC50 value of imatinib when compared with unmutated
      FIP1L1-PDGFRA. However, FIP1L1-PDGFRA/F604S more efficiently induced growth
      factor independence in cell lines and primary mouse bone marrow cells. Pulse
      chase analysis revealed that the F604S exchange strongly stabilized FIP1L1
      PDGFRA/F604S. The F604S mutation creates a binding site for the phosphatase
      domain of SHP-2, leading to lower autophosphorylation of FIP1L1-PDGFRA/F604S.
      This is associated with a reduced activation of SRC and CBL by FIP1L1
      PDGFRA/F604S compared with the unmutated oncogene. As SRC inhibition and
      knockdown resulted in FIP1L1-PDGFRA stabilization, this explains the extended
      half-life of FIP1L1-PDGFRA/F604S. Interestingly, FIP1L1-PDGFRA/L629P, a recently
      identified mutation in an imatinib-resistant CEL patient, also showed protein
      stabilization similar to that observed with FIP1L1-PDGFRA/F604S. Therefore,
      resistance mutations in FIP1L1-PDGFRA that do not interfere with drug binding but
      rather increase target protein stability seem to be one of the drug-resistance
      mechanisms in FIP1L1-PDGFRA-positive disease. 

PMID- 25761936
TI  - Expression of Multiple Taenia Solium Immunogens in Plant Cells Through a
      Ribosomal Skip Mechanism.
AB  - Taenia solium cysticercosis is a major parasitic disease that affects the human
      health and the economy in underdeveloped countries. Porcine cysticercosis, an
      obligatory stage in the parasite life cycle, is a suitable target for
      vaccination. While several recombinant and synthetic antigens proved to be
      effective as vaccines, the cost and logistic difficulties have prevented their
      massive use. Taking this into account, a novel strategy for developing a multi
      epitope low-cost vaccine is herein explored. The S3Pvac vaccine components
      (KETc1, KETc12, KETc7, and GK1 [KETc7]) and the protective HP6/TSOL18 antigen
      were expressed in a Helios2A polyprotein system, based on the 'ribosomal skip'
      mechanism mediated by the 2A sequence (LLNFDLLKLAGDVESNPG-P) derived from the
      Foot-and-mouth disease virus, which induces self-cleavage events at a
      translational level. This protein arrangement was expressed in transgenic tobacco
      cells. The inserted sequence and its transcript were detected in several Helios2A
      lines, with some lines showing recombinant protein accumulation levels up to 1.3
      ug/g of fresh weight in leaf tissues. The plant-derived Helios2A vaccine was
      recognized by antibodies in the cerebral spinal fluid from neurocysticercosis
      patients and elicited specific antibodies in BALB/c immunized mice. These
      evidences point to the Helios2A polyprotein as a promising system for expressing
      multiple antigens of interest for vaccination and diagnosis in one single
      construction.

PMID- 25761935
TI  - Deregulation of innate immune and inflammatory signaling in myelodysplastic
      syndromes.
AB  - Myelodysplastic syndromes (MDSs) are a group of heterogeneous clonal hematologic
      malignancies that are characterized by defective bone marrow (BM) hematopoiesis
      and by the occurrence of intramedullary apoptosis. During the past decade, the
      identification of key genetic and epigenetic alterations in patients has improved
      our understanding of the pathophysiology of this disease. However, the specific
      molecular mechanisms leading to the pathogenesis of MDS have largely remained
      obscure. Recently, essential evidence supporting the direct role of innate immune
      abnormalities in MDS has been obtained, including the identification of multiple
      key regulators that are overexpressed or constitutively activated in BM
      hematopoietic stem and progenitor cells. Mounting experimental results indicate
      that the dysregulation of these molecules leads to abnormal hematopoiesis,
      unbalanced cell death and proliferation in patients' BM, and has an important
      role in the pathogenesis of MDS. Furthermore, there is compelling evidence that
      the deregulation of innate immune and inflammatory signaling also affects other
      cells from the immune system and the BM microenvironment, which establish
      aberrant associations with hematopoietic precursors and contribute to the MDS
      phenotype. Therefore, the deregulation of innate immune and inflammatory
      signaling should be considered as one of the driving forces in the pathogenesis
      of MDS. In this article, we review and update the advances in this field,
      summarizing the results from the most recent studies and discussing their
      clinical implications. 

PMID- 25761937
TI  - Mechanisms of biofilm inhibition and degradation by antimicrobial peptides.
AB  - Many bacteria live as biofilms to cope with unfavourable surroundings. Biofilms
      start from (i) a planktonic stage, (ii) initial adhesion to surfaces and (iii)
      formation of sessile micro-colonies that secrete extracellular polymeric
      substance (EPS), leading to bacterial resistance to antibiotics. Antimicrobial
      peptides (AMPs) are extensively studied with regard to planktonic bacteria but
      much less so with regard to biofilm formation. In the present study, we
      investigated how the above three steps are affected by the properties of the AMPs
      using a series of peptides composed of six lysines and nine leucines, which
      differ in their sequences and hence their biophysical properties. Treatment with
      bactericidal peptides at non-inhibitory concentrations resulted in reduced
      biofilm growth, for some starting from 25 nM which is 0.2 and 0.4% of their
      minimum inhibitory concentration (MIC 6.3 and 12.5 MUM, respectively), continuing
      in a dose-dependent manner. We suggest that reduced bacterial adhesion to
      surfaces and decreased biofilm growth are due to the peptide's ability to coat
      either the biomaterial surface or the bacterium itself. Degradation of
      established biofilms by bactericidal and non-bactericidal peptides, within 1 h of
      incubation, occurs by either killing of embedded bacteria or detachment of live
      ones. In addition to shedding light on the mechanism of biofilm inhibition and
      degradation, these data may assist in the design of anti-biofilm AMPs. 

PMID- 25761938
TI  - Superior cycle performance and high reversible capacity of SnO2/graphene
      composite as an anode material for lithium-ion batteries.
AB  - SnO2/graphene composite with superior cycle performance and high reversible
      capacity was prepared by a one-step microwave-hydrothermal method using a
      microwave reaction system. The SnO2/graphene composite was characterized by X-ray
      diffraction, thermogravimetric analysis, Fourier-transform infrared spectroscopy,
      Raman spectroscopy, scanning electron microscope, X-ray photoelectron
      spectroscopy, transmission electron microscopy and high resolution transmission
      electron microscopy. The size of SnO2 grains deposited on graphene sheets is less
      than 3.5 nm. The SnO2/graphene composite exhibits high capacity and excellent
      electrochemical performance in lithium-ion batteries. The first discharge and
      charge capacities at a current density of 100 mA g(-1) are 2213 and 1402 mA h g(
      1) with coulomb efficiencies of 63.35%. The discharge specific capacities remains
      1359, 1228, 1090 and 1005 mA h g(-1) after 100 cycles at current densities of
      100, 300, 500 and 700 mA g(-1), respectively. Even at a high current density of
      1000 mA g(-1), the first discharge and charge capacities are 1502 and 876 mA h g(
      1), and the discharge specific capacities remains 1057 and 677 mA h g(-1) after
      420 and 1000 cycles, respectively. The SnO2/graphene composite demonstrates a
      stable cycle performance and high reversible capacity for lithium storage.

PMID- 25761939
TI  - Gut symptoms in diabetics correlate with components of the rectoanal inhibitory
      reflex, but not with pudendal nerve motor latencies or systemic autonomic
      neuropathy.
AB  - OBJECTIVE: Fecal incontinence (FI) occurs in up to 20% of diabetes mellitus (DM)
      patients. Rectoanal inhibitory reflex (RAIR) is an enteric anorectal reflex that
      reflects the integrity of mechanisms in the physiology of FI. We aimed to
      investigate whether diabetic patients with FI, not constipation, had prolongation
      of RAIR and altered gut-specific autonomic tone. METHODS: In this prospective
      case-matched study 31 type I DM (19 FI and 12 constipation) and 42 type II DM (26
      FI and 16 constipation). Another 21 participants were included as controls.
      Patients underwent the following assessments: cardiovagal autonomic tone
      (Modified Mayo Clinic composite autonomic severity score), rectal mucosal blood
      flow (RMBF) (assessment of gut-specific autonomic tone) and RAIR. Three phases of
      RAIR and the amplitude of maximal reflex relaxation were compared between groups.
      All participants completed symptom scores for FI and constipation. RESULTS: RAIR
      recovery time back to resting pressure was slower in diabetic patients with FI
      than controls (8.7 s vs 3.6 s, P < 0.05) and was an independent variable
      correlating with symptoms of FI (P < 0.05). RAIR recovery time was correlated
      with RMBF (r = 0.58, P = 0.04). CONCLUSION: RAIR is correlated with anorectal
      symptoms of FI and was associated with gut-specific autonomic neuropathy.

PMID- 25761940
TI  - Victimization and depression among youth with disabilities in the US child
      welfare system.
AB  - AIM: This study aimed to examine the prevalence of victimization among a United
      States-wide cohort of youth with disabilities (YWD) investigated for maltreatment
      in the child welfare system (CWS) and their correlation with mental health.
      METHODS: Data were drawn from baseline interviews in the second National Survey
      of Child and Adolescent Well-Being, a national representative survey of youth
      involved in the CWS. Interviews took place between 2008 and 2009 and included 675
      youth, 11-17 years old and residing with biological families across 83 counties
      nationwide. The sample consisted of 405 females (60.1%) and 270 males (39.9%),
      mean age = 13.5 years. We identified YWD if they reported one or more physical or
      neurodevelopmental health condition (n = 247). Reported victimization experiences
      and Children's Depression Inventory (CDI) scores were analysed using weighted
      regression analyses. RESULTS: One-quarter of YWD in the CWS reported three or
      more victimizations during the prior year compared with 19% of youth without
      disabilities. The odds of YWD reporting a one-unit increase in level of
      victimization was 75% higher (P < 0.05) than youth without disabilities.
      Prevalence of clinical depression was significantly higher among YWD (14 vs.
      5.5%; P < 0.05). Unlike youth without disabilities, the odds of clinical
      depression were 92% higher for every one-unit increase in victimization among
      YWD, controlling for covariates (P < 0.05). Of CWS-involved youth who reported
      three or more victimizations, 24.4% of YWD and 2.2% of non-disabled youth had CDI
      scores in the clinical range. CONCLUSION: YWDs in the US CWS are at high risk of
      experiencing victimization and clinical depression. Our findings suggest that
      health professionals need to screen CWS-involved YWD for multiple forms of
      victimization, and develop and implement trauma-informed services that target the
      mental health sequelae that may jeopardize their independence in adulthood.

PMID- 25761942
TI  - "Indefinite for Dysplasia" in Barrett's Esophagus: Inflammation and DNA Content
      Abnormality are Significant Predictors of Early Detection of Neoplasia.
AB  - BACKGROUND: Dysplasia arising from Barrett's esophagus precedes esophageal
      adenocarcinoma (EAC). Cases that are difficult to diagnose as dysplastic,
      especially in the setting of inflammation, may be designated "indefinite for
      dysplasia (IND)." Although flow cytometric analysis of DNA content has shown some
      promise in detecting EAC, there are few reports that have specifically evaluated
      the outcome of IND. AIMS AND METHODS: We analyzed a series of 96 IND patients
      seen at the University of Washington between 2005 and 2013 to determine the
      outcome of IND and to identify factors (including histologic features and DNA
      flow cytometric data) associated with subsequent detection of neoplasia. RESULTS:
      Twenty-five percent of IND cases were found to have low-grade dysplasia, high
      grade dysplasia (HGD), or EAC within 1 year, with 37% and 47% detected within 2
      and 3 years, respectively. The 1-, 2-, and 3-year detection rates of HGD or EAC
      were 10%, 13%, and 20%, respectively. Active inflammation (hazard ratio (HR)=3.4,
      P=0.0005) and abnormal DNA content (HR=5.7, P=0.003) were significant risk
      factors of neoplasia. When active inflammation and DNA flow cytometric results
      were considered together, the HR for the combined markers was 18.8 (P<0.0001).
      The sensitivity and specificity of the combined markers for predicting detection
      of subsequent neoplasia within 3 years were 100% and 60%, respectively, with 100%
      negative and 89% positive predictive values. CONCLUSIONS: Histology with the
      support of DNA flow cytometry can identify a subset of IND patients who may have
      a higher risk for subsequent detection of neoplasia.

PMID- 25761941
TI  - Dexmedetomidine inhibits Tetrodotoxin-resistant Nav1.8 sodium channel activity
      through Gi/o-dependent pathway in rat dorsal root ganglion neurons.
AB  - BACKGROUND: Systemically administered dexmedetomidine (DEX), a selective alpha2
      adrenergic receptor (alpha2-AR) agonists, produces analgesia and sedation.
      Peripherally restricted alpha2-AR antagonist could block the analgesic effect of
      systemic DEX on neuropathic pain, with no effect on sedation, indicating
      peripheral analgesic effect of DEX. Tetrodotoxin-resistant (TTX-R) sodium channel
      Nav1.8 play important roles in the conduction of nociceptive sensation. Both
      alpha2-AR and Nav1.8 are found in small nociceptive DRG neurons. We, therefore,
      investigated the effects of DEX on the Nav1.8 currents in acutely dissociated
      small-diameter DRG neurons. RESULTS: Whole-cell patch-clamp recordings
      demonstrated that DEX concentration-dependently suppressed TTX-R Nav1.8 currents
      in small-diameter lumbar DRG neurons. DEX also shifted the steady-state
      inactivation curves of Nav1.8 in a hyperpolarizing direction and increased the
      threshold of action potential and decrease electrical and chemical stimuli-evoked
      firings in small-diameter DRG neurons. The alpha2-AR antagonist yohimbine or
      alpha2A-AR antagonist BRL44408 but not alpha2B-AR antagonist imiloxan blocked the
      inhibition of Nav1.8 currents by DEX. Immunohistochemistry results showed that
      Nav1.8 was predominantly expressed in peripherin-positive small-diameter DRG
      neurons, and some of them were alpha2A-AR-positive ones. Our electrophysiological
      recordings also demonstrated that DEX-induced inhibition of Nav1.8 currents was
      prevented by intracellular application of G-protein inhibitor GDPbeta-s or Gi/o
      proteins inhibitor pertussis toxin (PTX), and bath application of adenylate
      cyclase (AC) activator forskolin or membrane-permeable cAMP analogue 8-Bromo-cAMP
      (8-Br-cAMP). PKA inhibitor Rp-cAMP could mimic DEX-induced inhibition of Nav1.8
      currents. CONCLUSIONS: We established a functional link between alpha2-AR and
      Nav1.8 in primary sensory neurons utilizing the Gi/o/AC/cAMP/PKA pathway, which
      probably mediating peripheral analgesia of DEX.

PMID- 25761943
TI  - Perioperative Outcomes of Proximal and Distal Gastric Bypass in Patients with BMI
      Ranged 50-60 kg/m(2)--A Double-Blind, Randomized Controlled Trial.
AB  - BACKGROUND: Proximal Roux-en-Y gastric bypass may not ensure adequate weight loss
      in superobese patients. Bypassing a longer segment of the small bowel may
      increase weight loss. The objective of the study was to compare the perioperative
      outcomes of laparoscopic proximal and distal gastric bypass in a double-blind
      randomized controlled trial of superobese patients. The study was conducted at
      two public tertiary care obesity centers in Norway. METHODS: Patients with body
      mass index (BMI) 50-60 kg/m(2) were randomly assigned to a proximal (150 cm
      alimentary limb) or a distal (150 cm common channel) gastric bypass. The
      biliopancreatic limb was 50 cm in both operations. Patients and follow-up
      personnel were blinded to the type of procedure. Thirty-day outcomes including
      complications are reported. RESULTS: We operated on 115 patients, of whom two
      were excluded at surgery, leaving 56 and 57 patients in the proximal group and
      distal group, respectively. The median (range) operating time was 72 (36-151) and
      101 (59-227) min, respectively (p < 0.001). Two distal procedures were converted
      to laparotomy during the primary procedure. Median length of hospital stay was 2
      (1-4) days in the proximal group and 2 (1-24) days in the distal group. The
      number of patients with complications and complications categorized according to
      the Contracted Accordion classification did not differ significantly. However,
      all six reoperations were performed in the distal group, of which three were
      completed by laparoscopy (p = 0.01 between groups). There were no deaths.
      CONCLUSIONS: In superobese patients with BMI between 50 and 60 kg/m(2), distal
      gastric bypass was associated with longer operating time and more severe
      complications resulting in reoperation than proximal gastric bypass.

PMID- 25761944
TI  - Long-term Results on Weight Loss and Diabetes Remission after Laparoscopic Sleeve
      Gastrectomy for A Morbidly Obese Chinese Population.
AB  - BACKGROUND: Laparoscopic sleeve gastrectomy (LSG) is an effective stand-alone
      bariatric procedure with favorable short-term results on weight reduction and
      comorbidity resolution. This study aims to evaluate the long-term results of LSG
      to see if weight reduction and diabetic improvement are sustainable. METHODS: We
      conducted a prospective observational study on patients receiving LSG as an index
      stand-alone bariatric operation in our unit. RESULTS: Between 2006 and 2014,
      there were 140 patients (91 females) aged 37.9 +/- 10.5 years with a body mass
      index of 41.0 +/- 7.0 kg/m(2). At 1-year (n = 123), 2-year (n = 99), 3-year (n =
      77), 4-year (n = 52), and 5-year (n = 44) follow-ups, the mean percentages of
      excess weight loss (%EWL) were 70.5, 65.2, 60.2, 53.2, and 57.2%, respectively,
      while the corresponding proportions with failed weight loss (%EWL <30%) were 7.3,
      9.1, 13.0, 25.0, and 22.7%. Weight regain (>25% rebound in %EWL) was evident with
      time as 0, 1.0, 11.6, 19.2, and 29.5% in the first 5-year follow-ups. In 65
      patients with type 2 diabetes mellitus, remission (complete and partial) was
      achieved in 34.5% at 1-year, 52.7% at 3-year, and 70.6% at 5-year follow-ups.
      Proportions of patients having optimal glycemic control (HbA1c <7%) increased
      significantly from 26.2% preoperatively to 80.9% at the first year and maintained
      at 78.6% at the fifth year (P < 0.001). CONCLUSIONS: LSG was effective in
      achieving substantial weight reduction and improved diabetic control for morbidly
      obese patients. Although weight regain was possible with time, majority of
      patients could maintain sustainable weight loss, diabetes remission, and glycemic
      improvement in the long run.

PMID- 25761946
TI  - The Parkinson Disease Mitochondrial Hypothesis: Where Are We at?
AB  - Parkinson's disease is a common, adult-onset neurodegenerative disorder whose
      pathogenesis is still under intense investigation. Substantial evidence from
      postmortem human brain tissue, genetic- and toxin-induced animal and cellular
      models indicates that mitochondrial dysfunction plays a central role in the
      pathophysiology of the disease. This review discusses our current understanding
      of Parkinson's disease-related mitochondrial dysfunction, including bioenergetic
      defects, mitochondrial DNA alterations, altered mitochondrial dynamics,
      activation of mitochondrial-dependent programmed cell death, and perturbations in
      mitochondrial tethering to the endoplasmic reticulum. Whether a primary or
      secondary event, mitochondrial dysfunction holds promise as a potential
      therapeutic target to halt the progression of neurodegeneration in Parkinson's
      disease.

PMID- 25761945
TI  - Recovery of a subtropical rocky shore is not yet complete, four years after a
      moderate sized oil spill.
AB  - Little is known about the recovery trajectory from small to moderate spills
      (<1000 t), particularly in the sub-tropics. On 11 March 2009 the MV Pacific
      Adventurer spilt 270 t of bunker fuel oil 13 km off Moreton Island, Australia,
      impacting wetlands, sandy beaches and rocky shores. This study examines the
      recovery of the rocky shore community four years after the spill. Results
      indicate that recovery on Moreton Island is taking longer than the 3-4 years
      suggested by the literature. The upper shore is recovering faster than the mid
      shore and is nearly recovered while the mid shore is still in the recovery
      process. These results indicate that small to moderate sized spills can have
      environmental impacts on par with much larger spills and emphasizes the need for
      a clear definition of a recovery endpoint. Long term studies are required to gain
      a full understanding of trajectories of recovery after oil spill impacts.

PMID- 25761947
TI  - Quantitative T2* magnetic resonance imaging for renal iron overload assessment:
      normal values by age and sex.
AB  - PURPOSE: Few studies of renal iron content have been performed with multiecho
      gradient-echo (ME-GRE) T2* magnetic resonance imaging (MRI). We assessed the
      feasibility and reproducibility of ME-GRE T2* MRI for measuring regional and
      global renal T2* values, and established the lower limits of normal in healthy
      subjects, also correlating the measured values with age and sex. METHODS: Twenty
      consecutive healthy subjects (13 men and 7 women, mean age 29.1 +/- 7.2 years,
      range 19-42 years) underwent MRI examinations using a 1.5 T magnet and an ME-GRE
      T2* sequence. For each kidney, T2* was measured in anterior, posterolateral, and
      posteromedial renal parenchymal regions. The mean T2* value was calculated as the
      average of the two kidneys T2* values. RESULTS: For the mean kidney T2* value,
      the coefficients of variation for intra- and inter-operator reproducibility were
      1.76% and 6.23%, respectively. The lower limit of normal for the mean kidney T2*
      value was 31 ms (median 51.39 +/- 10.09). There was no significant difference
      between left and right kidney T2* values (p = 0.578). No significant correlation
      was found between T2* values and subjects' age or sex. CONCLUSIONS: Renal ME-GRE
      T2* appears to be a feasible and reproducible technique. The renal T2* values
      showed no dependence on sex or age.

PMID- 25761948
TI  - The Na(+) -taurocholate cotransporting polypeptide knockout mouse: A new tool for
      study of bile acids and hepatitis B virus biology.

PMID- 25761949
TI  - Population susceptibility to a variant swine-origin influenza virus A(H3N2) in
      Vietnam, 2011-2012.
AB  - A reassortant swine-origin A(H3N2) virus (A/swine/BinhDuong/03-9/2010) was
      detected through swine surveillance programmes in southern Vietnam in 2010. This
      virus contains haemagglutinin and neuraminidase genes from a human A(H3N2) virus
      circulating around 2004-2006, and the internal genes from triple-reassortant
      swine influenza A viruses (IAVs). To assess population susceptibility to this
      virus we measured haemagglutination inhibiting (HI) titres to
      A/swine/BinhDuong/03-9/2010 and to seasonal A/Perth/16/2009 for 947 sera
      collected from urban and rural Vietnamese people during 2011-2012. Seroprevalence
      (HI ? 40) was high and similar for both viruses, with 62.6% [95% confidence
      interval (CI) 59.4-65.7] against A/Perth/16/2009 and 54.6% (95% CI 51.4-57.8%)
      against A/swine/BinhDuong/03-9/2010, and no significant differences between urban
      and rural participants. Children aged <5 years lacked antibodies to the swine
      origin H3 virus despite high seroprevalence for A/Perth/16/2009. These results
      reveal vulnerability to infection to this contemporary swine IAV in children aged
      <5 years; however, cross-reactive immunity in adults would likely limit epidemic
      emergence potential. 

PMID- 25761951
TI  - Early planning activity in frontal and parietal cortex in a simplified task.
AB  - Cortical planning activity has traditionally been probed with visual targets.
      However, external sensory signals might obscure early correlates of internally
      generated plans. We devised a nonspatial decision-making task in which the monkey
      is encouraged to decide randomly whether to reach or saccade in the absence of
      sensory stimuli. Neurons in frontal and parietal planning areas (in and around
      the arcuate and intraparietal sulci) showed responses predictive of the monkey's
      upcoming movement at early stages during the planning process. Neurons predicted
      the animal's future movements several seconds beforehand, sometimes before the
      trial even began. These data cast new light on the role of the cerebral cortex in
      the action planning process, when the animal is free to decide on his own actions
      in the absence of extraneous sensory cues. 

PMID- 25761950
TI  - Simultaneous recording of fluorescence and electrical signals by photometric
      patch electrode in deep brain regions in vivo.
AB  - Despite its widespread use, high-resolution imaging with multiphoton microscopy
      to record neuronal signals in vivo is limited to the surface of brain tissue
      because of limited light penetration. Moreover, most imaging studies do not
      simultaneously record electrical neural activity, which is, however, crucial to
      understanding brain function. Accordingly, we developed a photometric patch
      electrode (PME) to overcome the depth limitation of optical measurements and also
      enable the simultaneous recording of neural electrical responses in deep brain
      regions. The PME recoding system uses a patch electrode to excite a fluorescent
      dye and to measure the fluorescence signal as a light guide, to record electrical
      signal, and to apply chemicals to the recorded cells locally. The optical signal
      was analyzed by either a spectrometer of high light sensitivity or a
      photomultiplier tube depending on the kinetics of the responses. We used the PME
      in Oregon Green BAPTA-1 AM-loaded avian auditory nuclei in vivo to monitor
      calcium signals and electrical responses. We demonstrated distinct response
      patterns in three different nuclei of the ascending auditory pathway. On acoustic
      stimulation, a robust calcium fluorescence response occurred in auditory cortex
      (field L) neurons that outlasted the electrical response. In the auditory
      midbrain (inferior colliculus), both responses were transient. In the brain-stem
      cochlear nucleus magnocellularis, calcium response seemed to be effectively
      suppressed by the activity of metabotropic glutamate receptors. In conclusion,
      the PME provides a powerful tool to study brain function in vivo at a tissue
      depth inaccessible to conventional imaging devices. 

PMID- 25761952
TI  - Changes in motor unit behavior following isometric fatigue of the first dorsal
      interosseous muscle.
AB  - The neuromuscular strategies employed to compensate for fatigue-induced muscle
      force deficits are not clearly understood. This study utilizes surface
      electromyography (sEMG) together with recordings of a population of individual
      motor unit action potentials (MUAPs) to investigate potential compensatory
      alterations in motor unit (MU) behavior immediately following a sustained
      fatiguing contraction and after a recovery period. EMG activity was recorded
      during abduction of the first dorsal interosseous in 12 subjects at 20% maximum
      voluntary contraction (MVC), before and directly after a 30% MVC fatiguing
      contraction to task failure, with additional 20% MVC contractions following a 10
      min rest. The amplitude, duration and mean firing rate (MFR) of MUAPs extracted
      with a sEMG decomposition system were analyzed, together with sEMG root-mean
      square (RMS) amplitude and median frequency (MPF). MUAP duration and amplitude
      increased immediately postfatigue and were correlated with changes to sEMG MPF
      and RMS, respectively. After 10 min, MUAP duration and sEMG MPF recovered to
      prefatigue values but MUAP amplitude and sEMG RMS remained elevated. MU MFR and
      recruitment thresholds decreased postfatigue and recovered following rest. The
      increase in MUAP and sEMG amplitude likely reflects recruitment of larger MUs,
      while recruitment compression is an additional compensatory strategy directly
      postfatigue. Recovery of MU MFR in parallel with MUAP duration suggests a
      possible role for metabolically sensitive afferents in MFR depression
      postfatigue. This study provides insight into fatigue-induced neuromuscular
      changes by examining the properties of a large population of concurrently
      recorded single MUs and outlines possible compensatory strategies involving
      alterations in MU recruitment and MFR. 

PMID- 25761953
TI  - Precise visuotopic organization of the blind spot representation in primate V1.
AB  - The optic disk is a region of the retina consisting mainly of ganglion cell axons
      and blood vessels, which generates a visual scotoma known as the blind spot (BS).
      Information present in the surroundings of the BS can be used to complete the
      missing information. However, the neuronal mechanisms underlying these perceptual
      phenomena are poorly understood. We investigate the topography of the BS
      representation (BSR) in cortical area V1 of the capuchin monkey, using single and
      multiple electrodes. Receptive fields (RFs) of neurons inside the BSR were
      investigated using two distinct automatic bias-free mapping methods. The first
      method (local mapping) consisted of randomly flashing small white squares. For
      the second mapping method (global mapping), we used a single long bar that moved
      in one of eight directions. The latter stimulus was capable of eliciting neuronal
      activity inside the BSR, possibly attributable to long-range surround activity
      taking place outside the borders of the BSR. Importantly, we found that the
      neuronal activity inside the BSR is organized topographically in a manner similar
      to that found in other portions of V1. On average, the RFs inside the BS were
      larger than those outside. However, no differences in orientation or direction
      tuning were found between the two regions. We propose that area V1 exhibits a
      continuous functional topographic map, which is not interrupted in the BSR, as
      expected by the distribution of photoreceptors in the retina. Thus V1 topography
      is better described as "visuotopic" rather than as a discontinuous "retinotopic"
      map. 

PMID- 25761954
TI  - Direction of balance and perception of the upright are perceptually dissociable.
AB  - We examined whether the direction of balance rather than an otolith reference
      determines the perceived upright. Participants seated in a device that rotated
      around the roll axis used a joystick to control its motion. The direction of
      balance of the device, the location where it would not be accelerated to either
      side, could be offset from the gravitational vertical, a technique introduced by
      Riccio, Martin, and Stoffregen (J Exp Psychol Hum Percept Perform 18: 624-644,
      1992). Participants used the joystick to align themselves in different trials
      with the gravitational vertical, the direction of balance, the upright, or the
      direction that minimized oscillations. They pressed the joystick trigger whenever
      they thought they were at the instructed orientation. Achieved angles for the
      "align with gravity" and "align with the upright" conditions were not different
      from each other and were significantly displaced past the gravitational vertical
      opposite from the direction of balance. Mean indicated angles for align with
      gravity and align with the upright coincided with the gravitational vertical.
      Both mean achieved and indicated angles for the "minimize oscillations" and
      "align with the direction of balance" conditions were significantly deviated
      toward the gravitational vertical. Three control experiments requiring self
      settings to instructed orientations only, perceptual judgments only, and
      perceptual judgments during passive exposure to dynamic roll profiles confirmed
      that perception of the upright is determined by gravity, not by the direction of
      balance. 

PMID- 25761955
TI  - The effect of saccade metrics on the corollary discharge contribution to
      perceived eye location.
AB  - Corollary discharge (CD) is hypothesized to provide the movement information
      (direction and amplitude) required to compensate for the saccade-induced
      disruptions to visual input. Here, we investigated to what extent these conveyed
      metrics influence perceptual stability in human subjects with a target
      displacement detection task. Subjects made saccades to targets located at
      different amplitudes (4 degrees , 6 degrees , or 8 degrees ) and directions
      (horizontal or vertical). During the saccade, the target disappeared and then
      reappeared at a shifted location either in the same direction or opposite to the
      movement vector. Subjects reported the target displacement direction, and from
      these reports we determined the perceptual threshold for shift detection and
      estimate of target location. Our results indicate that the thresholds for all
      amplitudes and directions generally scaled with saccade amplitude. Additionally,
      subjects on average produced hypometric saccades with an estimated CD gain <1.
      Finally, we examined the contribution of different error signals to perceptual
      performance, the saccade error (movement-to-movement variability in saccade
      amplitude) and visual error (distance between the fovea and the shifted target
      location). Perceptual judgment was not influenced by the fluctuations in movement
      amplitude, and performance was largely the same across movement directions for
      different magnitudes of visual error. Importantly, subjects reported the correct
      direction of target displacement above chance level for very small visual errors
      (<0.75 degrees ), even when these errors were opposite the target-shift
      direction. Collectively, these results suggest that the CD-based compensatory
      mechanisms for visual disruptions are highly accurate and comparable for saccades
      with different metrics. 

PMID- 25761956
TI  - Optogenetically induced spatiotemporal gamma oscillations and neuronal spiking
      activity in primate motor cortex.
AB  - Transient gamma-band (40-80 Hz) spatiotemporal patterns are hypothesized to play
      important roles in cortical function. Here we report the direct observation of
      gamma oscillations as spatiotemporal waves induced by targeted optogenetic
      stimulation, recorded by intracortical multichannel extracellular techniques in
      macaque monkeys during their awake resting states. Microelectrode arrays
      integrating an optical fiber at their center were chronically implanted in
      primary motor (M1) and ventral premotor (PMv) cortices of two subjects. Targeted
      brain tissue was transduced with the red-shifted opsin C1V1(T/T). Constant (1-s
      square pulses) and ramp stimulation induced narrowband gamma oscillations during
      awake resting states. Recordings across 95 microelectrodes (4 * 4-mm array)
      enabled us to track the transient gamma spatiotemporal patterns manifested, e.g.,
      as concentric expanding and spiral waves. Gamma oscillations were induced well
      beyond the light stimulation volume, via network interactions at distal electrode
      sites, depending on optical power. Despite stimulation-related modulation in
      spiking rates, neuronal spiking remained highly asynchronous during induced gamma
      oscillations. In one subject we examined stimulation effects during preparation
      and execution of a motor task and observed that movement execution largely
      attenuated optically induced gamma oscillations. Our findings demonstrate that,
      beyond previously reported induced gamma activity under periodic drive, a
      prolonged constant stimulus above a certain threshold may carry primate motor
      cortex network dynamics into gamma oscillations, likely via a Hopf bifurcation.
      More broadly, the experimental capability in combining microelectrode array
      recordings and optogenetic stimulation provides an important approach for probing
      spatiotemporal dynamics in primate cortical networks during various physiological
      and behavioral conditions. 

PMID- 25761957
TI  - Interlimb communication following unexpected changes in treadmill velocity during
      human walking.
AB  - Interlimb reflexes play an important role in human walking, particularly when
      dynamic stability is threatened by external perturbations or changes in the
      walking surface. Interlimb reflexes have recently been demonstrated in the
      contralateral biceps femoris (cBF) following knee joint rotations applied to the
      ipsilateral leg (iKnee) during the late stance phase of human gait (Stevenson AJ,
      Geertsen SS, Andersen JB, Sinkjaer T, Nielsen JB, Mrachacz-Kersting N. J Physiol
      591: 4921-4935, 2013). This interlimb reflex likely acts to slow the forward
      progression of the body to maintain dynamic stability following the
      perturbations. We examined this hypothesis by unexpectedly increasing or
      decreasing the velocity of the treadmill before (-100 and -50 ms), at the same
      time, or following (+50 ms) the onset of iKnee perturbations in 12 healthy
      volunteers. We quantified the cBF reflex amplitude when the iKnee perturbation
      was delivered alone, the treadmill velocity change was delivered alone, or when
      the two perturbations were combined. When the treadmill velocity was suddenly
      increased (or decreased) 100 or 50 ms before the iKnee perturbations, the
      combined cBF reflex was significantly larger (or smaller) than the algebraic sum
      of the two perturbations delivered separately. Furthermore, unexpected changes in
      treadmill velocity increased the incidence of reflexes in other contralateral leg
      muscles when the iKnee perturbations were elicited alone. These results suggest a
      context dependency for interlimb reflexes. They also show that the cBF reflex
      changed in a predictable manner to slow the forward progression of the body and
      maintaining dynamic stability during walking, thus signifying a functional role
      for interlimb reflexes. 

PMID- 25761958
TI  - Involvement of protein kinase zeta in the maintenance of hippocampal long-term
      potentiation in rats with chronic visceral hypersensitivity.
AB  - The hippocampal long-term potentiation (LTP) was implicated in the formation of
      visceral hypersensitivity in rats with irritable bowel syndrome in our previous
      study. Recent studies have shown that protein kinase M zeta (PKMzeta) may be
      responsible for the maintenance of LTP in memory formation. However, it remains
      unclear whether PKMzeta is involved in the visceral hypersensitivity. In this
      study, a rat model of visceral hypersensitivity was generated by neonatal
      maternal separation (NMS). The visceral hypersensitivity was assessed by
      recording responses of the external oblique abdominal muscle to colorectal
      distension. Our results demonstrated that hippocampal LTP and visceral
      hypersensitivity were enhanced significantly in rats of NMS. zeta-Pseudosubstrate
      inhibitory peptide (ZIP) could dose dependently inhibit the maintenance of Cornu
      Ammonis area 1 LTP in rats of NMS. Furthermore, Western blot data showed that the
      expression of hippocampal phosphorylated PKMzeta (p-PKMzeta) significantly
      increased in rats of NMS. In addition, bilateral intrahippocampal injections of
      ZIP attenuated the visceral hypersensitivity dose dependently in rats of NMS. The
      maximal inhibition was observed at 30 min, and significant inhibition lasted for
      1.5-2 h after ZIP application. Besides, data from the open-field test and Morris
      water maze showed that ZIP did not influence the movement and spatial procedural
      memory in rats of NMS. In conclusion, p-PKMzeta might be a critical protein in
      the maintenance of hippocampal LTP, which could result in visceral
      hypersensitivity. 

PMID- 25761960
TI  - Common and metal-specific proteomic responses to cadmium and zinc in the metal
      tolerant ericoid mycorrhizal fungus Oidiodendron maius Zn.
AB  - Although adaptive metal tolerance may arise in fungal populations in polluted
      soils, the mechanisms underlying metal-specific tolerance are poorly understood.
      Comparative proteomics is a powerful tool to identify variation in protein
      profiles caused by changing environmental conditions, and was used to investigate
      protein accumulation in a metal tolerant isolate of the ericoid mycorrhizal
      fungus Oidiodendron maius exposed to zinc and cadmium. Two-dimensional gel
      electrophoresis and shotgun proteomics followed by mass spectrometry lead to the
      identification of common and metal-specific proteins and pathways. Proteins
      selectively induced by cadmium exposure were molecular chaperons of the Hsp90
      family, cytoskeletal proteins and components of the translation machinery. Zinc
      significantly up-regulated metabolic pathways related to energy production and
      carbohydrates metabolism, likely mirroring zinc adaptation of this fungal
      isolate. Common proteins induced by the two metal ions were the antioxidant
      enzyme Cu/Zn superoxide dismutase and ubiquitin. In mycelia exposed to zinc and
      cadmium, both proteomic techniques also identified agmatinase, an enzyme involved
      in polyamine biosynthesis. This novel finding suggests that, like plants,
      polyamines may have important functions in response to abiotic environmental
      stress in fungi. Genetic evidence also suggests that the biosynthesis of
      polyamines via an alternative metabolic pathway may be widespread in fungi. 

PMID- 25761959
TI  - The C957T polymorphism in the dopamine receptor D2 gene modulates domain-general
      category learning.
AB  - Adaptive learning from reward and punishment is vital for human survival.
      Striatal and frontal dopaminergic activities are associated with adaptive
      learning. For example, the C957T single nucleotide polymorphism of the dopamine
      receptor D2 (DRD2) gene alters striatal D2 receptor availability and affects
      individuals' adaptive learning ability. Specifically, individuals with the T/T
      genotype, which is associated with higher striatal D2 availability, show enhanced
      learning from negative outcomes. Prior work examining DRD2 genetic variability
      has focused primarily on frontally mediated reflective learning that is under
      effortful, conscious control. However, less is known about a more automatic,
      striatally mediated reflexive learning. Here we examined the extent to which this
      polymorphism differentially influences reflective and reflexive learning across
      visual and auditory modalities. We employed rule-based (RB) and information
      integration (II) category learning paradigms that target reflective and reflexive
      learning, respectively. Results revealed an advantage in II category learning but
      poorer RB category learning in T/T homozygotes. The pattern of results was
      consistent across sensory modalities. These findings suggest that this DRD2
      polymorphism exerts opposite influences on domain-general frontally mediated
      reflective learning and striatally mediated reflexive learning. 

PMID- 25761961
TI  - Homopolymers as structure-driving agents in semicrystalline block copolymer
      micelles.
AB  - A simplified hierarchical self-assembly strategy is presented in which
      homopolymer additives are used to manipulate the crystallization-driven self
      assembly of block copolymer micelles in selective media. By first incorporating
      the appropriate homopolymer chains within the micelle core, the system then
      evolves passively to yield crystalline platelets. These lamellae may be
      considered as self-assembled analogues of the traditional polymeric single
      crystal, which can be challenging or laborious to obtain otherwise. Used here as
      the test systems are micelles bearing polycaprolactone as the crystalline
      subphase in water and a mixed hydrophilic corona of poly(ethylene oxide) and
      poly(acrylic acid) the composition of which was varied methodically.
      Comicellization with homo-PCL has no influence at first; instead, the assemblies
      undergo morphological changes hierarchically, which were probed by electron
      microscopy and light scattering measurements. For all materials, the final
      product is consistently lamellar and micrometer-sized; however, lamellar shape
      variations are encountered as the stabilizing corona is altered. Such lamellae
      are unexpected based on the composition of most copolymers used here. The
      phenomenon also depends highly on the nature of the homo-PCL additive. A possible
      source for the activity of the homo-PCL is suggested, which also provides a
      strong basis to adapt the strategy for other crystalline materials. 

PMID- 25761962
TI  - Sucroferric oxyhydroxide: a review in hyperphosphataemia in chronic kidney
      disease patients undergoing dialysis.
AB  - Sucroferric oxyhydroxide (Velphoro(r)), an iron-based oral phosphate binder, is
      available for the control of serum phosphorus levels in patients with chronic
      kidney disease (CKD) on dialysis. In a pivotal phase III trial, sucroferric
      oxyhydroxide 1000-3000 mg/day for 24 weeks was noninferior to sevelamer carbonate
      4800-14,400 mg/day with regard to lowering serum phosphorus levels. Additionally,
      sucroferric oxyhydroxide at maintenance dosages was significantly more effective
      than low dosage sucroferric oxyhydroxide (250 mg/day) with regard to maintaining
      controlled serum phosphorus levels during weeks 24-27 of treatment. Sucroferric
      oxyhydroxide had a numerically lower mean daily pill burden and better treatment
      adherence than sevelamer carbonate. Treatment with sucroferric oxyhydroxide was
      generally well tolerated over 24 weeks' treatment, with the most frequently
      reported treatment-emergent adverse events being mild, transient diarrhoea and
      discoloured faeces. In a 28-week extension study, the efficacy and tolerability
      profile of sucroferric oxyhydroxide remained similar to sevelamer carbonate for
      up to 52 weeks. In conclusion, sucroferric oxyhydroxide is a valuable treatment
      option for hyperphosphataemia in CKD patients on dialysis, providing an effective
      and generally well tolerated noncalcium-based phosphate binder therapy with a
      lower pill burden than sevelamer carbonate and the potential for improved
      treatment adherence.

PMID- 25761963
TI  - Maternal Preeclampsia Is Associated With Reduced Adolescent Offspring Hip BMD in
      a UK Population-Based Birth Cohort.
AB  - A suboptimal intrauterine environment has been postulated to have adverse long
      term health effects, including an increased risk of osteoporosis. Because
      preeclampsia (PE) and to a lesser extent gestational hypertension (GH) are
      associated with impaired placental function, we postulated that these represent
      hitherto unrecognized risk factors for reduced bone mineral density (BMD) of the
      offspring. The objective of this study was to investigate if exposure to PE or GH
      in utero is associated with BMD of the offspring as measured in late adolescence.
      Mother-offspring pairs from the UK population-based cohort study, Avon
      Longitudinal Study of Parents and Children (ALSPAC), were investigated (n = 3088
      with relevant data). Multivariable linear regression was used to examine
      associations between PE/GH and total body, spine, and total hip BMD at age 17
      years. Of the 3088 mother-offspring pairs, 2% (n = 60) of the mothers fulfilled
      criteria for PE and 14% (n = 416) for GH. In confounder-adjusted analyses (ie,
      age of scan, gender, maternal factors, including BMI, offspring height, fat mass,
      and lean mass), PE was negatively associated with BMD at the hip (SD difference 
      0.30; 95%CI, -0.50 to -0.10). This association was not attenuated by further
      adjustment for gestational age and birth weight, which were hypothesized to be on
      the causal pathway. There was also weak evidence for a negative association
      between PE and total body BMD (SD difference -0.17; 95% CI, -0.36 to 0.02),
      whereas no relationship was evident at the spine (SD difference -0.11; 95% CI, 
      0.30 to 0.09). In contrast, a positive association of GH with offspring total
      body, hip, and spine BMD attenuated to the null with adjustment for confounders,
      in particular confounding via the maternal and offspring adiposity/size and the
      link between the two. Modest negative associations from exposure to PE, but not
      GH may represent a hitherto unrecognized risk factor for low BMD. Further
      exploration of the causal relationship of the in utero environment on subsequent
      offspring bone health is required.

PMID- 25761964
TI  - The survival difference between gastric cancer patients from the UK and Japan
      remains after weighted propensity score analysis considering all background
      factors.
AB  - BACKGROUND: Previous studies comparing survival between gastric cancer (GC)
      patients from the West and the East were based on the assumption that background
      factors and prognostic factors were identical. The aim of the current study was
      to compare the survival of GC patients from the UK and Japan using weighted
      propensity score analysis after identifying all different background factors.
      METHODS: Data from 464 patients from the Leeds Teaching Hospital NHS Trust,
      Leeds, UK (LTHT), and 465 patients from the Kanagawa Cancer Center Hospital,
      Yokohama, Japan (KCCH), who had surgery for GC were analyzed. Prognostic factors
      for overall survival (OS) and cancer-specific survival (CSS) were identified by
      univariate and multivariate analyses. Survival was compared by propensity score
      weighting after adjusting for all significantly different background factors.
      RESULTS: Most background factors were different between LTHT and KCCH patients.
      Unadjusted stage-specific OS and CSS were significantly better in KCCH.
      Independent prognostic factors for unadjusted OS and CSS were pT and pN in KCCH
      and in addition tumor location, pancreatectomy, resection margin status and
      number of examined lymph nodes in LTHT. Even after adjusting for all background
      characteristics, survival remained better in KCCH. CONCLUSIONS: These results
      suggest that differences in background factors are unable to fully explain the
      survival difference of GC patients between UK and Japan. Comprehensive studies
      into the biology of GC and/or host factors are needed to fully understand the
      survival difference.

PMID- 25761965
TI  - Multivariate longitudinal data analysis with mixed effects hidden Markov models.
AB  - Multiple longitudinal responses are often collected as a means to capture
      relevant features of the true outcome of interest, which is often hidden and not
      directly measurable. We outline an approach which models these multivariate
      longitudinal responses as generated from a hidden disease process. We propose a
      class of models which uses a hidden Markov model with separate but correlated
      random effects between multiple longitudinal responses. This approach was
      motivated by a smoking cessation clinical trial, where a bivariate longitudinal
      response involving both a continuous and a binomial response was collected for
      each participant to monitor smoking behavior. A Bayesian method using Markov
      chain Monte Carlo is used. Comparison of separate univariate response models to
      the bivariate response models was undertaken. Our methods are demonstrated on the
      smoking cessation clinical trial dataset, and properties of our approach are
      examined through extensive simulation studies. 

PMID- 25761966
TI  - Impact of fatty acid oxidation disorders in child neurology: from Reye syndrome
      to Pandora's box.

PMID- 25761968
TI  - Fast gaze reorientations by combined movements of the eye, head, trunk and lower
      extremities.
AB  - Large reorientations of the line of sight, involving combined rotations of the
      eyes, head, trunk and lower extremities, are executed either as fast single-step
      or as slow multiple-step gaze transfers. In order to obtain more insight into the
      mechanisms of gaze and multisegmental movement control, we have investigated time
      optimal gaze shifts (i.e. with the instruction to move as fast as possible)
      during voluntary whole-body rotations to remembered targets up to 180 degrees 
      eccentricity performed by standing healthy humans in darkness. Fast, accurate,
      single-step movement patterns occurred in approximately 70 % of trials, i.e.
      considerably more frequently than in previous studies with the instruction to
      turn at freely chosen speed (30 %). Head-in-space velocity in these cases was
      significantly higher than during multiple-step transfers and displayed a
      conspicuously regular bell-shaped profile, increasing smoothly to a peak and then
      decreasing slowly until realignment with the target. Head-in-space acceleration
      was on average not different during reorientations to the different target
      eccentricities. In contrast, head-in-space velocity increased with target
      eccentricity due to the longer duration of the acceleration phase implemented
      during trials to more distant targets. Eye saccade amplitude approached the eye
      in-orbit mechanical limit and was unrelated to eye/head velocity, duration or
      target eccentricity. Overall, the combined movement was stereotyped such that the
      first two principal components accounted for data variance almost up to gaze
      shift end, suggesting that the three mechanical degrees of freedom under
      consideration (eye-in-orbit, head-on-trunk and trunk-in-space) are on average
      reduced to two kinematic degrees of freedom (i.e. eye, head-in-space).
      Synchronous EMG activity in the anterior tibial and gastrocnemius muscles
      preceded the onset of eye rotation. Since the magnitude and timing of peak head
      in-space velocity were scaled with target eccentricity and because head-on-trunk
      and trunk-in-space displacements were on average linearly correlated, we propose
      a separate controller for head-in-space movement, whereas the movement of the eye
      in-space may be, in contrast, governed by global, i.e. gaze feedback. The rapid
      progression of the line of sight can be sustained, and the reactivation of the
      vestibulo-ocular reflex would be postponed, until gaze error approaches zero only
      in association with a strong head-in-space neural control signal.

PMID- 25761969
TI  - Probabilistic information on object weight shapes force dynamics in a grip-lift
      task.
AB  - Advance information, such as object weight, size and texture, modifies predictive
      scaling of grip forces in a grip-lift task. Here, we examined the influence of
      probabilistic advance information about object weight. Fifteen healthy volunteers
      repeatedly grasped and lifted an object equipped with a force transducer between
      their thumb and index finger. Three clearly distinguishable object weights were
      used. Prior to each lift, the probabilities for the three object weights were
      given by a visual cue. We examined the effect of probabilistic pre-cues on grip
      and lift force dynamics. We expected predictive scaling of grip force parameters
      to follow predicted values calculated according to probabilistic contingencies of
      the cues. We observed that probabilistic cues systematically influenced peak grip
      and load force rates, as an index of predictive motor scaling. However, the
      effects of probabilistic cues on force rates were nonlinear, and anticipatory
      adaptations of the motor output generally seemed to overestimate high
      probabilities and underestimate low probabilities. These findings support the
      suggestion that anticipatory adaptations and force scaling of the motor system
      can integrate probabilistic information. However, probabilistic information seems
      to influence motor programs in a nonlinear fashion. 

PMID- 25761970
TI  - Regulation of Intracellular Copper by Induction of Endogenous Metallothioneins
      Improves the Disease Course in a Mouse Model of Amyotrophic Lateral Sclerosis.
AB  - Mutations in SOD1 cause amyotrophic lateral sclerosis (ALS), an incurable motor
      neuron disease. The pathogenesis of the disease is poorly understood, but
      intracellular copper dyshomeostasis has been implicated as a key process in the
      disease. We recently observed that metallothioneins (MTs) are an excellent target
      for the modification of copper dyshomeostasis in a mouse model of ALS
      (SOD1(G93A)). Here, we offer a therapeutic strategy designed to increase the
      level of endogenous MTs. The upregulation of endogenous MTs by dexamethasone, a
      synthetic glucocorticoid, significantly improved the disease course and rescued
      motor neurons in SOD1(G93A) mice, even if the induction was initiated when peak
      body weight had decreased by 10%. Neuroprotection was associated with the
      normalization of copper dyshomeostasis, as well as with decreased levels of
      SOD1(G93A) aggregates. Importantly, these benefits were clearly mediated in a MT
      dependent manner, as dexamethasone did not provide any protection when endogenous
      MTs were abolished from SOD1(G93A) mice. In conclusion, the upregulation of
      endogenous MTs represents a promising strategy for the treatment of ALS linked to
      mutant SOD1.

PMID- 25761971
TI  - Erratum to: TDP-43 Proteinopathy and ALS: Insights into Disease Mechanisms and
      Therapeutic Targets.

PMID- 25761973
TI  - Automated patient-specific optimization of three-dimensional double-inversion
      recovery magnetic resonance imaging.
AB  - PURPOSE: To automatically optimize three-dimensional double-inversion recovery
      (3D-DIR) MRI of the brain on a patient-by-patient basis. METHODS: DIR is a
      powerful MRI technique that allows simultaneous suppression of white matter (WM)
      and cerebrospinal fluid (CSF) in brain imaging. Unfortunately, the tissue
      suppression is not always consistent across patients. We propose patient-specific
      optimization of WM suppression for improved gray matter (GM)-WM contrast.
      Relaxation times were measured in the same scan session, and through real time
      processing were used for calculating DIR inversion times for maximum tissue
      contrast. Signal evolution during the variable-flip-angle turbo-spin-echo readout
      was calculated using the extended phase graph algorithm. Patient-specific
      optimization was examined in five healthy volunteers and two multiple sclerosis
      patients. Two volunteers were scanned twice for reproducibility. The contrast
      ratios, GM signal-to-noise ratio (SNR), and image histogram were used to assess
      the performance of this patient-specific approach. RESULTS: Automated
      optimization of 3D-DIR was successfully completed in all experiments with
      processing time of ~1 min. GM-WM contrast ratio tripled with the optimized DIR
      sequence, with only a 19% decrease in GM-CSF contrast and 30% SNR penalty.
      CONCLUSION: Patient-specific optimization is feasible and significantly improves
      GM-WM contrast on 3D-DIR with a moderate decrease in the GM SNR.

PMID- 25761972
TI  - microRNA-200b as a Switch for Inducible Adult Angiogenesis.
AB  - SIGNIFICANCE: Angiogenesis is the process by which new blood vessels develop from
      a pre-existing vascular system. It is required for physiological processes such
      as developmental biology and wound healing. Angiogenesis also plays a crucial
      role in pathological conditions such as tumor progression. The underlying
      importance of angiogenesis necessitates a highly regulated process. RECENT
      ADVANCES: Recent works have demonstrated that the process of angiogenesis is
      regulated by small noncoding RNA molecules called microRNAs (miRs). These miRs,
      collectively referred to as angiomiRs, have been reported to have a profound
      effect on the process of angiogenesis by acting as either pro-angiogenic or anti
      angiogenic regulators. CRITICAL ISSUES: In this review, we will discuss the role
      of miR-200b as a regulator of angiogenesis. Once the process of angiogenesis is
      complete, anti-angiogenic miR-200b has been reported to provide necessary
      braking. Downregulation of miR-200b has been reported across various tumor types,
      as deregulated angiogenesis is necessary for tumor development. Transient
      downregulation of miR-200b in wounds drives wound angiogenesis. FUTURE
      DIRECTIONS: New insights and understanding of the molecular mechanism of
      regulation of angiogenesis by miR-200b has opened new avenues of possible
      therapeutic interventions to treat angiogenesis-related patho-physiological
      conditions. Antioxid. Redox Signal. 22, 1257-1272.

PMID- 25761974
TI  - Assessing Susceptibility to Epilepsy in Three Rat Strains Using Brain Metabolic
      Profiling Based on HRMAS NMR Spectroscopy and Chemometrics.
AB  - The possibility that a metabolomic approach can inform about the pathophysiology
      of a given form of epilepsy was addressed. Using chemometric analyses of HRMAS
      NMR data, we compared several brain structures in three rat strains with
      different susceptibilities to absence epilepsy: Genetic Absence Epilepsy Rats
      from Strasbourg (GAERS), Non Epileptic Control rats (NEC), and Wistar rats. Two
      ages were investigated: 14 days postnatal (P14) before the onset of seizures and
      5 month old adults with fully developed seizures (Adults). The relative
      concentrations of 19 metabolites were assessed using (1)H HRMAS NMR experiments.
      Univariate and multivariate analyses including multiblock models were used to
      identify the most discriminant metabolites. A strain-dependent evolution of
      glutamate, glutamine, scyllo-inositol, alanine, and glutathione was highlighted
      during cerebral maturation. In Adults, data from somatosensory and motor cortices
      allowed discrimination between GAERS and NEC rats with higher levels of scyllo
      inositol, taurine, and phosphoethanolamine in NEC. This epileptic metabolic
      phenotype was in accordance with current pathophysiological hypothesis of absence
      epilepsy (i.e., seizure-generating and control networks) and putative resistance
      of NEC rats and was observed before seizure onset. This methodology could be very
      efficient in a clinical context. 

PMID- 25761975
TI  - Growth of a deep-water, predatory fish is influenced by the productivity of a
      boundary current system.
AB  - The effects of climate change on predatory fishes in deep shelf areas are
      difficult to predict because complex processes may govern food availability and
      temperature at depth. We characterised the net impact of recent environmental
      changes on hapuku (Polyprion oxygeneios), an apex predator found in continental
      slope habitats (>200 m depth) by using dendrochronology techniques to develop a
      multi-decadal record of growth from otoliths. Fish were sampled off temperate
      south-western Australia, a region strongly influenced by the Leeuwin Current, a
      poleward-flowing, eastern boundary current. The common variance among individual
      growth records was relatively low (3.4%), but the otolith chronology was
      positively correlated (r = 0.61, p < 0.02) with sea level at Fremantle, a proxy
      for the strength of the Leeuwin Current. The Leeuwin Current influences the
      primary productivity of shelf ecosystems, with a strong current favouring growth
      in hapuku. Leeuwin Current strength is predicted to decline under climate change
      models and this study provides evidence that associated productivity changes may
      flow through to higher trophic levels even in deep water habitats. 

PMID- 25761976
TI  - Structure based investigation on the binding interaction of transport proteins in
      leishmaniasis: insights from molecular simulation.
AB  - Leishmania major is the causative agent of cutaneous leishmaniasis which affects
      over 1 million people in 88 different countries. The incidence of this disease is
      on the rise due to the current problems associated with the present
      chemotherapeutics. In addition, Leishmania confronts resistance to the
      traditional drugs like sodium stibogluconate and newer repurposed drugs like
      miltefosine. ABC transporters are involved in the development of drug resistance.
      Miltefosine, the drug used for the treatment of leishmaniasis, is effluxed by P4
      ATPase and ABC transporter, which is the prime focus of our study in this paper.
      P4 ATPase (MDR1) along with an unnamed protein (cdc50) translocates miltefosine
      from the outer to the inner leaflet by the process of flipping which is ATP
      driven. In contrast, miltefosine also escapes from the cells by an energy
      dependent mechanism that involves the ABC transporter protein (ABC). It is known
      that certain genes in the parasite amplify the portions of a gene which encodes
      ABC transporter and P4 ATPase involved in translocating phospholipids and hence
      resistance to miltefosine. We observed the ABC and P4 ATPase genes, 39 T-box
      elements were observed in the ABC transporter protein and three elements were
      observed in the P4 ATPase gene suggesting its role in transcription regulation.
      To the best of our knowledge, there are no structural and regulatory reports on
      these two proteins in L. major. Computational structural biology tools may aid in
      understanding the interaction of miltefosine with the P4-ATPase-cdc50 complex and
      the ABC transporter. This can be achieved by modeling the target protein
      structures, studying the dynamics associated with the different domains of the
      protein and later using activators and inhibitors to alter the functioning of the
      protein. Molecular dynamics simulation with a lipid bilayer is performed to
      investigate the conformational changes and structure-activity relationship. As
      transporters are difficult to model, the relevant structural motifs and domains
      may help to understand the allosteric relation with the substrate and the
      cofactors. The dynamics of a protein molecule ultimately defines the functional
      mechanism involving excursions of multiple conformational states. To understand
      these functional mechanisms of transporter proteins, computational modeling and
      simulations will be carried out with the goal of elucidating the atomistic
      details of allosteric conformational transitions and propagations during the
      transport processes. In particular these studies are designed to investigate the
      critical structural and dynamic elements that determine individual and combined
      ligand-binding specificities, the interactions among transporters, their coupled
      proteins and the associations of transporters within the lipid bilayer. The
      nature of results from such studies also makes it possible to rationally optimize
      existing ligands for these proteins and develop some new compounds that can shift
      the conformational equilibrium of transporters which may aid in functional
      studies leading to drug discovery. 

PMID- 25761978
TI  - A paper-based skin patch for the diagnostic screening of cystic fibrosis.
AB  - A thin and flexible paper-based skin patch was developed for the diagnostic
      screening of cystic fibrosis. It utilized a unique combination of both anion
      exchange and pH test papers to enable the quantitative, colorimetric and on-skin
      detection of sweat anions. 

PMID- 25761977
TI  - Efficacy and tolerability of saxagliptin compared with glimepiride in elderly
      patients with type 2 diabetes: a randomized, controlled study (GENERATION).
AB  - AIMS: To assess the efficacy and safety of adjunctive saxagliptin vs glimepiride
      in elderly patients with type 2 diabetes (T2D) and inadequate glycaemic control.
      METHODS: In this multinational, randomized, double-blind, phase IIIb/IV study
      (GENERATION; NCT01006603), patients aged >=65 years were randomized (1 : 1) to
      receive saxagliptin 5 mg/day or glimepiride <=6 mg/day, added to metformin,
      during a 52-week treatment period. The primary endpoint was achievement of
      glycated haemoglobin (HbA1c) <7.0% at week 52 without confirmed/severe
      hypoglycaemia. The key secondary endpoint was incidence of confirmed/severe
      hypoglycaemia. Safety and tolerability were also assessed. RESULTS: Of 720
      patients randomized (360 in each treatment group; mean age 72.6 years; mean T2D
      duration 7.6 years), 574 (79.8%) completed the study (saxagliptin 80.3%;
      glimepiride 79.2%). Similar proportions of patients achieved the primary endpoint
      with saxagliptin and glimepiride (37.9 vs 38.2%; odds ratio 0.99, 95% confidence
      interval 0.73, 1.34; p = 0.9415); however, a significant treatment-by-age
      interaction effect was detected (p = 0.0389): saxagliptin was numerically (but
      not significantly) superior to glimepiride for patients aged <75 years (39.2 vs
      33.3%) and numerically inferior for patients aged >=75 years (35.9 vs 45.5%). The
      incidence of confirmed/severe hypoglycaemia was lower with saxagliptin vs
      glimepiride (1.1 vs 15.3%; nominal p < 0.0001). Saxagliptin was generally well
      tolerated, with similar incidences of adverse events compared with glimepiride.
      CONCLUSION: As avoiding hypoglycaemia is a key clinical objective in elderly
      patients, saxagliptin is a suitable alternative to glimepiride in patients with
      T2D aged >=65 years.

PMID- 25761979
TI  - Doctor Shopping Behavior for Zolpidem Among Insomnia Patients in Taiwan: A
      Nationwide Population-Based Study.
AB  - OBJECTIVES: Although zolpidem is listed as a controlled drug in Taiwan, patients'
      behavior has not been restricted and has led to the problem of doctor shopping
      behavior (DSB), leading to overutilization of medical resources and excess
      spending. The National Health Insurance Administration in Taiwan has instituted a
      new policy to regulate physicians' prescribing behavior and decrease DSB. This
      retrospective study aimed to analyze the DSB for zolpidem by insomnia patients
      and assess related factors. DESIGN AND PARTICIPANTS: Data were extracted from the
      Longitudinal Health Insurance Database in Taiwan. Individuals with a diagnosis of
      insomnia who received more than one prescription of zolpidem in 2008 were
      followed for 24 mo. Doctor shopping was defined as >= 2 prescriptions by
      different doctors within >= 1 day overlapping in the duration of therapy. The
      percentage of zolpidem obtained through doctor shopping was used as an indicator
      of the DSB of each patient. RESULTS: Among the 6,947 insomnia patients who were
      prescribed zolpidem, 1,652 exhibited DSB (23.78%). The average dose of zolpidem
      dispensed for each patient during 24 mo was 244.21 daily defined doses. The
      doctor shopping indicator (DSI) was 0.20 (standard deviation, 0.23) among
      patients with DSB. Younger age, chronic diseases, high number of diseases, higher
      premium status, high socioeconomic status, and fewer people served per practicing
      physicians were all factors significantly related to doctor shopping behavior.
      CONCLUSION: Doctor shopping for zolpidem appears to be an important issue in
      Taiwan. Implementing a proper referral system with efficient data exchange by
      physician or pharmacist-led medication reconciliation process might reduce DSB.

PMID- 25761980
TI  - The Impact of Untreated Obstructive Sleep Apnea on Cardiopulmonary Complications
      in General and Vascular Surgery: A Cohort Study.
AB  - STUDY OBJECTIVE: To determine whether preoperatively untreated obstructive sleep
      apnea (OSA) affects postoperative outcomes. DESIGN: Cohort study of patients
      undergoing surgery between July 2012 and September 2013, utilizing prospectively
      collected data from the Michigan Surgical Quality Collaborative. Multivariable
      regression models were used to compare complication rates between treated and
      untreated OSA, while adjusting for important patient covariates and clustering
      within hospitals. SETTING: Fifty-two community and academic hospitals in
      Michigan. PATIENTS: Adult patients undergoing various general or vascular
      operations were categorized as: (1) no diagnosis or low risk of OSA; (2)
      documented OSA without therapy or suspicion of OSA; and (3) diagnosis of OSA with
      treatment (e.g., positive airway pressure). EXPOSURES: OSA, preoperatively
      treated or untreated, was the exposure variable. Postoperative 30-day
      cardiopulmonary complications including arrhythmias, cardiac arrest, myocardial
      infarction, unplanned reintubation, pulmonary embolism, and pneumonia were the
      outcomes of interest. MEASUREMENTS AND RESULTS: Of 26,842 patients, 2,646 (9.9%)
      had a diagnosis or suspicion of OSA. Of those, 1,465 (55.4%) were untreated.
      Patient and procedural risk factors were evenly balanced between treated and
      untreated groups. Compared with treated OSA, untreated OSA was independently
      associated with more cardiopulmonary complications (risk-adjusted rates 6.7%
      versus 4.0%; adjusted odds ratio [aOR] = 1.8, P = 0.001), particularly unplanned
      reintubations (aOR = 2.5, P = 0.003) and myocardial infarction (aOR = 2.6, P =
      0.031). CONCLUSIONS: Patients with obstructive sleep apnea (OSA) who are not
      treated with positive airway pressure preoperatively are at increased risks for
      cardiopulmonary complications after general and vascular surgery. Improving the
      recognition of OSA and ensuring adequate treatment may be a strategy to reduce
      risk for surgical patients with OSA.

PMID- 25761982
TI  - The Effect of Body Position on Physiological Factors that Contribute to
      Obstructive Sleep Apnea.
AB  - STUDY OBJECTIVES: Obstructive sleep apnea (OSA) resolves in lateral sleep in 20%
      of patients. However, the effect of lateral positioning on factors contributing
      to OSA has not been studied. We aimed to measure the effect of lateral
      positioning on the key pathophysiological contributors to OSA including lung
      volume, passive airway anatomy/collapsibility, the ability of the airway to
      stiffen and dilate, ventilatory control instability (loop gain), and arousal
      threshold. DESIGN: Non-randomized single arm observational study. SETTING: Sleep
      laboratory. PATIENTS/PARTICIPANTS: 20 (15M, 5F) continuous positive airway
      pressure (CPAP)-treated severe OSA patients. INTERVENTIONS: Supine vs. lateral
      position. MEASUREMENTS: CPAP dial-downs performed during sleep to measure: (i)
      Veupnea: asleep ventilatory requirement, (ii) passive V0: ventilation off CPAP
      when airway dilator muscles are quiescent, (iii) Varousal: ventilation at which
      respiratory arousals occur, (iv) active V0: ventilation off CPAP when airway
      dilator muscles are activated during sleep, (v) loop gain: the ratio of the
      ventilatory drive response to a disturbance in ventilation, (vi) arousal
      threshold: level of ventilatory drive which leads to arousal, (vii) upper airway
      gain (UAG): ability of airway muscles to restore ventilation in response to
      increases in ventilatory drive, and (viii) pharyngeal critical closing pressure
      (Pcrit). Awake functional residual capacity (FRC) was also recorded. RESULTS:
      Lateral positioning significantly increased passive V0 (0.33 +/- 0.76L/min vs.
      3.56 +/- 2.94L/min, P < 0.001), active V0 (1.10 +/- 1.97L/min vs. 4.71 +/-
      3.08L/min, P < 0.001), and FRC (1.31 +/- 0.56 L vs. 1.42 +/- 0.62 L, P = 0.046),
      and significantly decreased Pcrit (2.02 +/- 2.55 cm H2O vs. -1.92 +/- 3.87 cm
      H2O, P < 0.001). Loop gain, arousal threshold, Varousal, and UAG were not
      significantly altered. CONCLUSIONS: Lateral positioning significantly improves
      passive airway anatomy/collapsibility (passive V0, pharyngeal critical closing
      pressure), the ability of the airway to stiffen and dilate (active V0), and the
      awake functional residual capacity without improving loop gain or arousal
      threshold.

PMID- 25761981
TI  - Regional Cerebral Blood Flow during Wakeful Rest in Older Subjects with Mild to
      Severe Obstructive Sleep Apnea.
AB  - OBJECTIVES: To evaluate changes in regional cerebral blood flow (rCBF) during
      wakeful rest in older subjects with mild to severe obstructive sleep apnea (OSA)
      and healthy controls, and to identify markers of OSA severity that predict
      altered rCBF. DESIGN: High-resolution (99m)Tc-HMPAO SPECT imaging during wakeful
      rest. SETTING: Research sleep laboratory affiliated with a University hospital.
      PARTICIPANTS: Fifty untreated OSA patients aged between 55 and 85 years, divided
      into mild, moderate, and severe OSA, and 20 age-matched healthy controls.
      INTERVENTIONS: N/A. MEASUREMENTS: Using statistical parametric mapping, rCBF was
      compared between groups and correlated with clinical, respiratory, and sleep
      variables. RESULTS: Whereas no rCBF change was observed in mild and moderate
      groups, participants with severe OSA had reduced rCBF compared to controls in the
      left parietal lobules, left precentral gyrus, bilateral postcentral gyri, and
      right precuneus. Reduced rCBF in these regions and in areas of the bilateral
      frontal and left temporal cortex was associated with more hypopneas, snoring,
      hypoxemia, and sleepiness. Higher apnea, microarousal, and body mass indexes were
      correlated to increased rCBF in the basal ganglia, insula, and limbic system.
      CONCLUSIONS: While older individuals with severe obstructive sleep apnea (OSA)
      had hypoperfusion in the sensorimotor and parietal areas, respiratory variables
      and subjective sleepiness were correlated with extended regions of hypoperfusion
      in the lateral cortex. Interestingly, OSA severity, sleep fragmentation, and
      obesity correlated with increased perfusion in subcortical and medial cortical
      regions. Anomalies with such a distribution could result in cognitive deficits
      and reflect impaired vascular regulation, altered neuronal integrity, and/or
      undergoing neurodegenerative processes.

PMID- 25761984
TI  - Erratum.
AB  - [This corrects the article DOI: 10.1177/2050640614540154.]. 

PMID- 25761983
TI  - A Biphasic Change of Regional Blood Volume in the Frontal Cortex during Non-Rapid
      Eye Movement Sleep: A Near-Infrared Spectroscopy Study.
AB  - STUDY OBJECTIVES: Current knowledge on hemodynamics in sleep is limited because
      available techniques do not allow continuous recordings and mainly focus on
      cerebral blood flow while neglecting other important parameters, such as blood
      volume (BV) and vasomotor activity. DESIGN: Observational study. PARTICIPANTS AND
      SETTINGS: Continuous measures of hemodynamics over the left forehead and biceps
      were performed using near-infrared spectroscopy (NIRS) during nocturnal
      polysomnography in 16 healthy participants in sleep laboratory. MEASUREMENTS AND
      RESULTS: Temporal dynamics and mean values of cerebral and muscular oxygenated
      hemoglobin (HbO2), deoxygenated hemoglobin (HHb), and BV during different sleep
      stages were compared. A biphasic change of cerebral BV was observed which
      contrasted a monotonic increase of muscular BV during non-rapid eye movement
      sleep. A significant decrement in cerebral HbO2 and BV accompanied by an increase
      of HHb was recorded at sleep onset (Phase I). Prior to slow wave sleep (SWS) HbO2
      and BV turned to increase whereas HHb began to decrease in subsequent Phase II
      suggested increased brain perfusion during SWS. The cerebral HbO2 slope
      correlated to BV slope in Phase I and II, but it only correlated to HHb slope in
      Phase II. The occurrence time of inflection points correlated to SWS latencies.
      CONCLUSION: Initial decrease of brain perfusion with decreased blood volume (BV)
      and oxygenated hemoglobin (HbO2) together with increasing muscular BV fit
      thermoregulation process at sleep onset. The uncorrelated and correlated slopes
      of HbO2 and deoxygenated hemoglobin indicate different mechanisms underlying the
      biphasic hemodynamic process in light sleep and slow wave sleep (SWS). In SWS,
      changes in vasomotor activity (i.e., increased vasodilatation) may mediate
      increasing cerebral and muscular BV.

PMID- 25761985
TI  - TA-periodic ("601"-like) centromeric nucleosomes of A. thaliana.
AB  - The bulk of strong nucleosomes (SNs, with visibly periodic DNA sequences) is
      described by consensus pattern of 5 or 6 base runs of purines alternating with
      similar runs of pyrimidines - RR/YY SNs. Yet, the strongest known nucleosome
      positioning sequence, the 601 clone of Lowary and Widom, is rather periodic
      repetition of TA dinucleotides following one another every 10 bases. We located
      "601"-like TA-periodic sequences in the genome of A. thaliana. Several families
      of such sequences are discovered repeating almost exclusively in centromeres.
      Thus, while A. thaliana SNs of RR/YY type have strong affinity to pericentromeric
      regions, as it has been previously found, the SNs of TA periodic type concentrate
      rather in centromeres. 

PMID- 25761986
TI  - Ethnicity, Obesity and Emotional Factors Associated With Gestational
      Hypertension.
AB  - Identifying factors that can be related to the occurrence of gestational arterial
      hypertension. The sample was composed by 105 pregnant women in their third
      trimester of gestation, during the period between September 2013 and August 2014.
      General assessment questionnaires together with a questionnaire to evaluate
      anxiety (STAI-A-STATE) were applied; arterial blood pressure values were
      collected. To classify anxiety, a mean of the final result of all the
      questionnaires gotten was calculated. Pregnant women who showed scores higher
      than the mean were considered anxious. All data were analyzed by a logistic
      regression. The significance level adopted was 0.05. A data analysis allowed us
      to verify that 92.38% of the pregnant women had an anxious personality STAI-A
      STATE and 12.38% of them had a momentary hypertension. The momentary hypertension
      showed a correlation between the hypertension and the state anxiety score (p =
      0.049). The hypertension showed an association with the presence of depression
      (OR 8.69), obesity (OR 6.45), anxiety (OR 7.77), nausea (OR 12.79) and non-white
      race (OR 8.18). According to the study realized, the factors non-white race,
      depression, nausea, obesity and anxiety can be considered risk factors for the
      occurrence of gestational arterial hypertension. Based on these findings, a high
      quality prenatal assistance is considered of prime importance.

PMID- 25761987
TI  - Bone marrow-derived progenitor cells in de novo liver regeneration in liver
      transplant.
AB  - The study was designed (1) to examine the hypothesis that circulating progenitor
      cells play a role in the process of de novo regeneration in human liver
      transplants and that these cells arise from a cell population originating in, or
      associated with, the bone marrow and (2) to investigate whether the transplanted
      liver volume has an effect on the circulating recipient-derived progenitor cells
      that generate hepatocytes during this process. Clinical data and liver tissue
      characteristics were analyzed in male individuals who underwent sex-mismatched
      adult-to-adult living donor liver transplantation using dual left lobe grafts.
      Dual left lobe grafts were examined at the time of transplantation and 19 to 27
      days after transplantation. All recipients showed recovery of normal liver
      function and a significant increase in the volume of the engrafted left lobes
      after transplantation. Double staining for a Y-chromosome probe and the CD31
      antigen showed the presence of hybrid vessels composed of recipient-derived cells
      and donor cells within the transplanted liver tissues. Furthermore, CD34
      expressing cells were observed commingling with Y-chromosome+ cells. The ratio of
      recipient-derived vessels and the number of Y+ CD34+ cells tended to be higher
      when smaller graft volumes underwent transplantation. These findings suggest that
      the recruitment of circulating bone marrow-derived progenitor cells could
      contribute to vessel formation and de novo regeneration in human liver
      transplants. Moreover, graft volume may be an important determinant for the
      active mobilization of circulating recipient-derived progenitor cells and their
      contribution to liver regeneration.

PMID- 25761988
TI  - Less incidence of coronary artery disease in general anesthesia compared to
      spinal-epidural anesthesia after total knee replacement: 90-day follow-up period
      by a population-based dataset.
AB  - Total knee replacement (TKR) is an effective and safe procedure. However, large
      scale study to compare the incidence of coronary artery disease (CAD) after
      spinal or epidural anesthesia (SA-EA) or general anesthesia (GA) for TKR has not
      ever been conducted. To do so, we studied a population-based dataset from the
      Taiwan National Health Research Institute and hypothesized that the incidence of
      CAD might be different with regional than with general anesthesia. The risk of
      CAD-related events during a 90-day follow-up period among patients who received
      TKR under SA-EA or GA was evaluated in the present study. A total of 1500
      patients from the Taiwan National Health Insurance claims database who underwent
      TKR from January 1, 2004, to December 31, 2006, were allocated into two groups.
      Group 1 included 1012 patients who received SA-EA during TKR procedure. Group 2
      included 488 patients who received GA during this procedure. The number of
      patients who developed CAD during the 90-day follow-up period was 31 (3.1 %) in
      group 1 and 6 (1.2 %) in group 2. The Kaplan-Meier survival analysis of IHD-free
      cumulative survival rate during the 90-day follow-up period for patients who
      underwent TKR was significantly lower in group 1 than in group 2. The hazard
      ratio for the occurrence of CAD was 2.80 (95 % CI 1.16-6.78), and the hazard was
      higher for patients who received SA-EA than for patients who received GA after
      adjusted potential confounding factors. After the performance of TKR, patients
      had a potentially increased risk for CAD in SA-EA compared to GA during the 90
      day follow-up period.

PMID- 25761990
TI  - Activity report 2014.

PMID- 25761989
TI  - Production of diacetyl by metabolically engineered Enterobacter cloacae.
AB  - Diacetyl, a high value product that can be extensively used as a food ingredient,
      could be produced from the non-enzymatic oxidative decarboxylation of alpha
      acetolactate during 2,3-butanediol fermentation. In this study, the 2,3
      butanediol biosynthetic pathway in Enterobacter cloacae subsp. dissolvens strain
      SDM, a good candidate for microbial 2,3-butanediol production, was reconstructed
      for diacetyl production. To enhance the accumulation of the precursor of
      diacetyl, the alpha-acetolactate decarboxylase encoding gene (budA) was knocked
      out in strain SDM. Subsequently, the two diacetyl reductases DR-I (gdh) and DR-II
      (budC) encoding genes were inactivated in strain SDM individually or in
      combination to decrease the reduction of diacetyl. Although the engineered strain
      E. cloacae SDM (DeltabudADeltabudC) was found to have a good ability for diacetyl
      production, more alpha-acetolactate than diacetyl was produced simultaneously. In
      order to enhance the nonenzymatic oxidative decarboxylation of alpha-acetolactate
      to diacetyl, 20 mM Fe(3+) was added to the fermentation broth at the optimal
      time. In the end, by using the metabolically engineered strain E. cloacae SDM
      (DeltabudADeltabudC), diacetyl at a concentration of 1.45 g/L was obtained with a
      high productivity (0.13 g/(L.h)). The method developed here may be a promising
      process for biotechnological production of diacetyl. 

PMID- 25761991
TI  - Illumina MiSeq sequencing investigation on the contrasting soil bacterial
      community structures in different iron mining areas.
AB  - Mine activities leaked heavy metals into surrounding soil and may affected
      indigenous microbial communities. In the present study, the diversity and
      composition of the bacterial community in soil collected from three regions which
      have different pollution degree, heavy pollution, moderate pollution, and non
      pollution, within the catchment of Chao River in Beijing City, were compared
      using the Illumina MiSeq sequencing technique. Rarefaction results showed that
      the polluted area had significant higher bacterial alpha diversity than those
      from unpolluted area. Principal component analysis (PCA) showed that microbial
      communities in the polluted areas had significant differences compared with the
      unpolluted area. Moreover, PCA at phylum level and Matastats results demonstrated
      that communities in locations shared similar phyla diversity, indicating that the
      bacterial community changes under metal pollution were not reflected on phyla
      structure. At genus level, the relative abundance of dominant genera changed in
      sites with degrees of pollution. Genera Bradyrhizobium, Rhodanobacter,
      Reyranella, and Rhizomicrobium significantly decreased with increasing pollution
      degree, and their dominance decreased, whereas several genera (e.g.,
      Steroidobacter, Massilia, Arthrobacter, Flavisolibacter, and Roseiflexus)
      increased and became new dominant genera in the heavily metal-polluted area. The
      potential resistant bacteria, found within the genera of Thiobacillus,
      Pseudomonas, Arthrobacter, Microcoleus, Leptolyngbya, and Rhodobacter, are less
      than 2.0 % in the indigenous bacterial communities, which play an important role
      in soil ecosystem. This effort to profile the background diversity may set the
      first stage for better understanding the mechanism underlying the community
      structure changes under in situ mild heavy metal pollution.

PMID- 25761992
TI  - Leaching of copper and nickel in soil-water systems contaminated by bauxite
      residue (red mud) from Ajka, Hungary: the importance of soil organic matter.
AB  - Red mud is a highly alkaline (pH >12) waste product from bauxite ore processing.
      The red mud spill at Ajka, Hungary, in 2010 released 1 million m(3) of caustic
      red mud into the surrounding area with devastating results. Aerobic and anaerobic
      batch experiments and solid phase extraction techniques were used to assess the
      impact of red mud addition on the mobility of Cu and Ni in soils from near the
      Ajka spill site. Red mud addition increases aqueous dissolved organic carbon
      (DOC) concentrations due to soil alkalisation, and this led to increased mobility
      of Cu and Ni complexed to organic matter. With Ajka soils, more Cu was mobilised
      by contact with red mud than Ni, despite a higher overall Ni concentration in the
      solid phase. This is most probably because Cu has a higher affinity to form
      complexes with organic matter than Ni. In aerobic experiments, contact with the
      atmosphere reduced soil pH via carbonation reactions, and this reduced organic
      matter dissolution and thereby lowered Cu/Ni mobility. These data show that the
      mixing of red mud into organic rich soils is an area of concern, as there is a
      potential to mobilise Cu and Ni as organically bound complexes, via soil
      alkalisation. This could be especially problematic in locations where anaerobic
      conditions can prevail, such as wetland areas contaminated by the spill.

PMID- 25761993
TI  - Aortic stenosis begets aortic stenosis: between a rock and a hard place?

PMID- 25761995
TI  - Adult patients with Fabry disease: what does the cardiologist need to know?

PMID- 25761994
TI  - Prognostic impact of blood pressure response plus gadolinium enhancement in
      dilated cardiomyopathy.
AB  - OBJECTIVE: Late gadolinium enhancement (LGE) is not necessarily ideal for
      detecting diffuse myocardial fibrosis in idiopathic dilated cardiomyopathy (DCM).
      Since systolic blood pressure response (SBPR) during exercise has been proposed
      to reflect cardiac pump reserve in patients with heart failure, we wished to
      determine whether LGE plus SBPR is a better prognostic factor in patients with
      DCM. METHODS: LGE and cardiopulmonary exercise testing results in consecutive 207
      patients with DCM were examined. Patients were divided into four groups according
      to the presence or absence of LGE and the SBPR cut-off value of +40 mm Hg
      according to receiver operating characteristic curve analysis: LGE-positive+SBPR
      <40 mm Hg (n=65), LGE-positive+SBPR >=40 mm Hg (n=40), LGE-negative+SBPR <40 mm
      Hg (n=33) and LGE-negative+SBPR >=40 mm Hg (n=69). The composite end point was
      cardiac death, cardiac transplantation, LV assist device implantation, life
      threatening arrhythmia or heart failure. RESULTS: Forty-two (20%) patients
      developed the composite end point, with rates of 35%, 20%, 21% and 6% in patients
      with LGE-positive+SBPR <40 mm Hg, LGE-positive+SBPR >=40 mm Hg, LGE-negative+SBPR
      <40 mm Hg and LGE-negative+SBPR >=40 mm Hg status, respectively. Multivariable
      Cox regression analysis identified LGE-positive and SBPR <40 mm Hg as a
      significant independent predictor of cardiac events (HR 2.08, 95% CI 1.06 to
      4.11, p=0.034). Of note, there was no significant difference in the cardiac event
      free survival rate between the LGE-positive+SBPR >=40 mm Hg and LGE-negative+SBPR
      <40 mm Hg groups (p=0.736). CONCLUSIONS: The combination of LGE and SBPR provides
      more clinically relevant information for assessing the risk of cardiac events in
      patients with DCM than LGE status alone.

PMID- 25761997
TI  - Stereotactic body radiotherapy in operable patients with stage I NSCLC: where is
      the evidence?
AB  - This review summarizes the evidence of stereotactic body radiotherapy (SBRT) as
      an alternative to surgery (lobectomy and sublobar resection) for stage I NSCLC.
      Three randomized trials comparing SBRT and surgery were initiated but all three
      were stopped early due to poor accrual. As the next level of evidence, results
      from matched-pair analyses performed in single-institutional (n = 4), multi
      institutional (n = 3) and population-based (n = 3) settings are available. There
      was close agreement between all studies that SBRT is at least equivalent to
      sublobar resection making it the preferred treatment for a high-risk population.
      SBRT was equivalent to lobectomy in the endpoints of loco-regional control and
      cancer-specific survival. Disease-free survival and overall survival were
      inferior after SBRT compared with lobectomy in one and two studies, respectively,
      and not significantly different in all other studies. Consequently, for patients
      without relevant comorbidities, who are accepting the risk of a surgical
      procedure, lobectomy remains the standard of care. 

PMID- 25761996
TI  - Targeting bacteria via iminoboronate chemistry of amine-presenting lipids.
AB  - Synthetic molecules that target specific lipids serve as powerful tools for
      understanding membrane biology and may also enable new applications in
      biotechnology and medicine. For example, selective recognition of bacterial
      lipids may give rise to novel antibiotics, as well as diagnostic methods for
      bacterial infection. Currently known lipid-binding molecules primarily rely on
      noncovalent interactions to achieve lipid selectivity. Here we show that targeted
      recognition of lipids can be realized by selectively modifying the lipid of
      interest via covalent bond formation. Specifically, we report an unnatural amino
      acid that preferentially labels amine-presenting lipids via iminoboronate
      formation under physiological conditions. By targeting phosphatidylethanolamine
      and lysylphosphatidylglycerol, the two lipids enriched on bacterial cell
      surfaces, the iminoboronate chemistry allows potent labelling of Gram-positive
      bacteria even in the presence of 10% serum, while bypassing mammalian cells and
      Gram-negative bacteria. The covalent strategy for lipid recognition should be
      extendable to other important membrane lipids. 

PMID- 25761999
TI  - Who wants to become a general practitioner? Student and curriculum factors
      associated with choosing a GP career--a multivariable analysis with particular
      consideration of practice-orientated GP courses.
AB  - OBJECTIVE: Because of the increasing shortage of general practitioners (GPs) in
      many countries, this study aimed to explore factors related to GP career choice
      in recent medical graduates. Particular focus was placed on the impact of
      specific practice-orientated GP courses at different stages of the medical
      undergraduate curriculum. DESIGN: Observational study. Multivariable binary
      logistic regression was used to reveal independent associations with career
      choice. SETTING: Leipzig Medical School, Germany. SUBJECTS: 659 graduates
      (response rate = 64.2%). MAIN OUTCOME MEASURE: Choice of general practice as a
      career. RESULTS: Six student-associated variables were found to be independently
      related to choice of general practice as a career: age, having family or friends
      in general practice, consideration of a GP career at matriculation, preference
      for subsequent work in a rural or small-town area, valuing the ability to see a
      broad spectrum of patients, and valuing long-term doctor-patient relationships.
      Regarding the curriculum, after adjustment independent associations were found
      with a specific pre-clinical GP elective (OR = 2.6, 95% CI 1.3-5.3), a four-week
      GP clerkship during the clinical study section (OR = 2.6, 95% CI 1.3-5.0), and a
      four-month GP clinical rotation during the final year (OR = 10.7, 95% CI 4.3
      26.7). It was also found that the work-related values of the female participants
      were more compatible with those of physicians who opt for a GP career than was
      the case for their male colleagues. CONCLUSION: These results support the
      suggestion that a practice-orientated GP curriculum in both the earlier and later
      stages of undergraduate medical education raises medical schools' output of
      future GPs. The findings are of interest for medical schools (curriculum design,
      admission criteria), policy-makers, and GPs involved in undergraduate medical
      education. More research is needed on the effectiveness of specific educational
      interventions in promoting interest in general practice as a career.

PMID- 25761998
TI  - Distinct genetic architecture underlies the emergence of sleep loss and prey
      seeking behavior in the Mexican cavefish.
AB  - BACKGROUND: Sleep is characterized by extended periods of quiescence and reduced
      responsiveness to sensory stimuli. Animals ranging from insects to mammals adapt
      to environments with limited food by suppressing sleep and enhancing their
      response to food cues, yet little is known about the genetic and evolutionary
      relationship between these processes. The blind Mexican cavefish, Astyanax
      mexicanus is a powerful model for elucidating the genetic mechanisms underlying
      behavioral evolution. A. mexicanus comprises an extant ancestral-type surface
      dwelling morph and at least five independently evolved cave populations.
      Evolutionary convergence on sleep loss and vibration attraction behavior, which
      is involved in prey seeking, have been documented in cavefish raising the
      possibility that enhanced sensory responsiveness underlies changes in sleep.
      RESULTS: We established a system to study sleep and vibration attraction behavior
      in adult A. mexicanus and used high coverage quantitative trait loci (QTL)
      mapping to investigate the functional and evolutionary relationship between these
      traits. Analysis of surface-cave F2 hybrid fish and an outbred cave population
      indicates that independent genetic factors underlie changes in sleep/locomotor
      activity and vibration attraction behavior. High-coverage QTL mapping with
      genotyping-by-sequencing technology identify two novel QTL intervals that
      associate with locomotor activity and include the narcolepsy-associated tp53
      regulating kinase. These QTLs represent the first genomic localization of
      locomotor activity in cavefish and are distinct from two QTLs previously
      identified as associating with vibration attraction behavior. CONCLUSIONS: Taken
      together, these results localize genomic regions underlying sleep/locomotor and
      sensory changes in cavefish populations and provide evidence that sleep loss
      evolved independently from enhanced sensory responsiveness.

PMID- 25762000
TI  - A phase I open-labeled, single-arm, dose-escalation, study of dichloroacetate
      (DCA) in patients with advanced solid tumors.
AB  - Purpose Preclinical evidence suggests dichloroacetate (DCA) can reverse the
      Warburg effect and inhibit growth in cancer models. This phase 1 study was
      undertaken to assess the safety, recommended phase 2 dose (RP2D), and
      pharmacokinetic (PK) profile of oral DCA in patients with advanced solid tumors.
      Patients and Methods Twenty-four patients with advanced solid malignancies were
      enrolled using a standard 3 + 3 protocol at a starting dose of 6.25 mg/kg twice
      daily (BID). Treatment on 28 days cycles was continued until progression,
      toxicity, or consent withdrawal. PK samples were collected on days 1 and 15 of
      cycle 1, and day 1 of subsequent cycles. PET imaging ((18) F-FDG uptake) was
      investigated as a potential biomarker of response. Results Twenty-three evaluable
      patients were treated with DCA at two doses: 6.25 mg/kg and 12.5 mg/kg BID
      (median of 2 cycles each). No DLTs occurred in the 6.25 mg/kg BID cohort so the
      dose was escalated. Three of seven patients had DLTs (fatigue, vomiting,
      diarrhea) at 12.5 mg/kg BID. Thirteen additional patients were treated at 6.25
      mg/kg BID. Most toxicities were grade 1-2 with the most common being fatigue,
      neuropathy and nausea. No responses were observed and eight patients had stable
      disease. The DCA PK profile in cancer patients was consistent with previously
      published data. There was high variability in PK values and neuropathy among
      patients. Progressive increase in DCA trough levels and a trend towards decreased
      (18) F-FDG uptake with length of DCA therapy was observed. Conclusions The RP2D
      of oral DCA is 6.25 mg/kg BID. Toxicities will require careful monitoring in
      future trials.

PMID- 25762001
TI  - Expression of coxsackievirus and adenovirus receptor separates hematopoietic and
      cardiac progenitor cells in fetal liver kinase 1-expressing mesoderm.
AB  - In developing embryos or in vitro differentiation cultures using pluripotent stem
      cells (PSCs), such as embryonic stem cells and induced pluripotent stem cells,
      fetal liver kinase 1 (Flk1)-expressing mesodermal cells are thought to be a
      heterogeneous population that includes hematopoietic progenitors, endothelial
      progenitors, and cardiac progenitors. However, information on cell surface
      markers for separating these progenitors in Flk1+ cells is currently limited. In
      the present study, we show that distinct types of progenitor cells in Flk1+ cells
      could be separated according to the expression of coxsackievirus and adenovirus
      receptor (CAR, also known as CXADR), a tight junction component molecule. We
      found that mouse and human PSC- and mouse embryo-derived Flk1+ cells could be
      subdivided into Flk1+CAR+ cells and Flk1+CAR- cells. The progenitor cells with
      cardiac potential were almost entirely restricted to Flk1+CAR+ cells, and
      Flk1+CAR- cells efficiently differentiated into hematopoietic cells. Endothelial
      differentiation potential was observed in both populations. Furthermore, from the
      expression of CAR, Flk1, and platelet-derived growth factor receptor-alpha
      (PDGFRalpha), Flk1+ cells could be separated into three populations
      (Flk1+PDGFRalpha- CAR- cells, Flk1+PDGFRalpha-CAR+ cells, and
      Flk1+PDGFRalpha+CAR+ cells). Flk1+PDGFRalpha+ cells and Flk1+PDGFRalpha- cells
      have been reported as cardiac and hematopoietic progenitor cells, respectively.
      We identified a novel population (Flk1+PDGFRalpha- CAR+ cells) with the potential
      to differentiate into not only hematopoietic cells and endothelial cells but also
      cardiomyocytes. Our findings indicate that CAR would be a novel and prominent
      marker for separating PSC- and embryo-derived Flk1+ mesodermal cells with
      distinct differentiation potentials.

PMID- 25762002
TI  - Pluripotent cell models of fanconi anemia identify the early pathological defect
      in human hemoangiogenic progenitors.
AB  - Fanconi anemia (FA) is a disorder of genomic instability characterized by
      progressive bone marrow failure (BMF), developmental abnormalities, and an
      increased susceptibility to cancer. Although various consequences in
      hematopoietic stem/progenitor cells have been attributed to FA-BMF, the quest to
      identify the initial pathological event is still ongoing. To address this issue,
      we established induced pluripotent stem cells (iPSCs) from fibroblasts of six
      patients with FA and FANCA mutations. An improved reprogramming method yielded
      iPSC-like colonies from all patients, and iPSC clones were propagated from two
      patients. Quantitative evaluation of the differentiation ability demonstrated
      that the differentiation propensity toward the hematopoietic and endothelial
      lineages is already defective in early hemoangiogenic progenitors. The expression
      levels of critical transcription factors were significantly downregulated in
      these progenitors. These data indicate that the hematopoietic consequences in FA
      patients originate from the early hematopoietic stage and highlight the potential
      usefulness of iPSC technology for elucidating the pathogenesis of FA-BMF. 

PMID- 25762003
TI  - Nanofabrication of tailored surface structures in dielectrics using temporally
      shaped femtosecond-laser pulses.
AB  - We have investigated the use of tightly focused, temporally shaped femtosecond
      (fs)-laser pulses for producing nanostructures in two dielectric materials
      (sapphire and phosphate glass) with different characteristics in their response
      to pulsed laser radiation. For this purpose, laser pulses shaped by third-order
      dispersion (TOD) were used to generate temporally asymmetric excitation pulses,
      leading to the single-step production of subwavelength ablative and subablative
      surface structures. When compared to previous works on the interaction of tightly
      focused TOD-shaped pulses with fused silica, we show here that this approach
      leads to very different nanostructure morphologies, namely, clean nanopits
      without debris surrounding the crater in sapphire and well-outlined nanobumps and
      nanovolcanoes in phosphate glass. Although in sapphire the debris-free processing
      is associated with the much lower viscosity of the melt compared to fused silica,
      nanobump formation in phosphate glass is caused by material network expansion
      (swelling) upon resolidification below the ablation threshold. The formation of
      nanovolcanoes is a consequence of the combined effect of material network
      expansion and ablation occurring in the periphery and central part of the
      irradiated region, respectively. It is shown that the induced morphologies can be
      efficiently controlled by modulating the TOD coefficient of the temporally shaped
      pulses. 

PMID- 25762004
TI  - Pathogenesis, clinical course and neuro-radiological signs of Proprionibacterium
      acnes cerebritis: Case report and literature review.
AB  - The clinical and neuroimaging characteristics of brain infections related to
      Propionibacterium acnes are not well-characterized, making early diagnosis and
      treatment a challenge. More recently, life-threatening central nervous system
      infections with P. acnes are being reported with increasing frequency as
      complications of neurointerventional procedures. We present a rare case of P.
      acnes cerebritis that occurred as a sequela of bare platinum aneurysm coiling and
      a contaminant of percutaneous angiographic intervention. We include an extensive
      review of the literature describing the pathogenesis of P. acnes and neuro
      radiological signs of brain infections related to this pathogen. 

PMID- 25762006
TI  - [Molecular causes of leukemia : systematic clinical and preclinical research].

PMID- 25762005
TI  - Construction of stable packaging cell lines for clinical lentiviral vector
      production.
AB  - Lentiviral vectors are useful experimental tools for stable gene delivery and
      have been used to treat human inherited genetic disorders and hematologic
      malignancies with promising results. Because some of the lentiviral vector
      components are cytotoxic, transient plasmid transfection has been used to produce
      the large batches needed for clinical trials. However, this method is costly,
      poorly reproducible and hard to scale up. Here we describe a general method for
      construction of stable packaging cell lines that continuously produce lentiviral
      vectors. This uses Cre recombinase-mediated cassette exchange to insert a codon
      optimised HIV-1 Gag-Pol expression construct in a continuously expressed locus in
      293FT cells. Subsequently Rev, envelope and vector genome expression cassettes
      are serially transfected. Vector titers in excess of 10(6) transducing units/ml
      can be harvested from the final producer clones, which can be increased to 10(8)
      TU/ml by concentration. This method will be of use to all basic and clinical
      investigators who wish to produce large batches of lentiviral vectors. 

PMID- 25762007
TI  - [Diabetic nephropathy: current diagnostics and treatment].
AB  - Diabetic kidney disease is a leading cause of renal failure in Germany.
      Albuminuria is an early diagnostic indicator of renal damage in diabetes and,
      aside from renal failure, a major risk factor of cardiovascular disease. An early
      diagnosis of diabetic kidney disease is of great importance to reduce associated
      cardiovascular mortality; glycemic control should aim for HbA1c levels of < 7 %.
      Guidelines on blood pressure differ, but it should generally be reduced to <
      140/90 mmHg; stricter limits should be applied if albuminuria is present. ACE
      inhibitors (ACE-I) or angiotensin receptor blockers (ARB) should be preferred for
      blood pressure control. A combination of ACE-Is and ARBs or a renin-inhibitor
      therapy does not improve cardiovascular outcome, instead it increases the rate of
      adverse events, e.g., hyperkalemia or renal failure. Lipid control, usually with
      statins, should be started at an early phase of renal failure. Vitamin D receptor
      activation and uric acid reduction might play a future role in the treatment of
      diabetic kidney disease. Pharmacological modification of inflammatory signaling
      appears to be promising but is not yet of clinical relevance. 

PMID- 25762008
TI  - [Treatment of hepatitis C].
AB  - Chronic hepatitis C virus (HCV) infection is the major cause of liver cirrhosis,
      hepatocellular carcinoma and liver transplantation in the western world. The
      development and approval of nine directly acting antiviral drugs in recent years
      has led to a dramatic improvement in therapeutic efficacy accompanied by fewer
      side effects. With current treatment options sustained virologic response in more
      than 90 % of patients can be achieved depending on HCV genotype, liver cirrhosis
      and prior therapies. Modern HCV treatment regimens are interferon-free and should
      be administered for 12-24 weeks. Shorter courses are possible in selected
      patients. For the treatment of HCV genotype 1 infection combinations of either
      the nucleotide polymerase inhibitor sofosbuvir with the protease inhibitor
      simeprevir or with one of the two NS5A inhibitors daclatasvir or ledipasvir on
      the one hand or triple DAA therapy of paritaprevir, ombitasvir and dasabuvir on
      the other hand are applicable. Ribavirin has still a role as an add-on in
      difficult to treat patients. 

PMID- 25762009
TI  - Action of obestatin in skeletal muscle repair: stem cell expansion, muscle
      growth, and microenvironment remodeling.
AB  - The development of therapeutic strategies for skeletal muscle diseases, such as
      physical injuries and myopathies, depends on the knowledge of regulatory signals
      that control the myogenic process. The obestatin/GPR39 system operates as an
      autocrine signal in the regulation of skeletal myogenesis. Using a mouse model of
      skeletal muscle regeneration after injury and several cellular strategies, we
      explored the potential use of obestatin as a therapeutic agent for the treatment
      of trauma-induced muscle injuries. Our results evidenced that the overexpression
      of the preproghrelin, and thus obestatin, and GPR39 in skeletal muscle increased
      regeneration after muscle injury. More importantly, the intramuscular injection
      of obestatin significantly enhanced muscle regeneration by simulating satellite
      stem cell expansion as well as myofiber hypertrophy through a kinase hierarchy.
      Added to the myogenic action, the obestatin administration resulted in an
      increased expression of vascular endothelial growth factor (VEGF)/vascular
      endothelial growth factor receptor 2 (VEGFR2) and the consequent
      microvascularization, with no effect on collagen deposition in skeletal muscle.
      Furthermore, the potential inhibition of myostatin during obestatin treatment
      might contribute to its myogenic action improving muscle growth and regeneration.
      Overall, our data demonstrate successful improvement of muscle regeneration,
      indicating obestatin is a potential therapeutic agent for skeletal muscle injury
      and would benefit other myopathies related to muscle regeneration. 

PMID- 25762010
TI  - Feature integration in the mapping of multi-attribute visual stimuli to
      responses.
AB  - In the human visual system, different attributes of an object, such as shape and
      color, are separately processed in different modules and then integrated to
      elicit a specific response. In this process, different attributes are thought to
      be temporarily "bound" together by focusing attention on the object; however, how
      such binding contributes to stimulus-response mapping remains unclear. Here we
      report that learning and performance of stimulus-response tasks was more
      difficult when three attributes of the stimulus determined the correct response
      than when two attributes did. We also found that spatially separated
      presentations of attributes considerably complicated the task, although they did
      not markedly affect target detection. These results are consistent with a paired
      attribute model in which bound feature pairs, rather than object representations,
      are associated with responses by learning. This suggests that attention does not
      bind three or more attributes into a unitary object representation, and long-term
      learning is required for their integration. 

PMID- 25762011
TI  - Ras Activity Oscillates in the Mouse Suprachiasmatic Nucleus and Modulates
      Circadian Clock Dynamics.
AB  - Circadian rhythms, generated in the mouse suprachiasmatic nucleus (SCN), are
      synchronized to the environmental day-night changes by photic input. The
      activation of the extracellular signal-regulated kinases 1 and 2 (ERK1,2) and
      cAMP response element-binding protein (CREB)-mediated transcription play a
      critical role in this photoentrainment. The small GTPase Ras is one of the major
      upstream regulators of the ERK1,2/CREB pathway. In contrast to the well-described
      role of Ras in structural and functional synaptic plasticity in the adult mouse
      brain, the physiological regulation of Ras by photic sensory input is yet
      unknown. Here, we describe for the first time a circadian rhythm of Ras activity
      in the mouse SCN. Using synRas transgenic mice, expressing constitutively
      activated V12-Ha-Ras selectively in neurons, we demonstrate that enhanced Ras
      activation causes shortening of the circadian period length. We found upregulated
      expression and decreased inhibitory phosphorylation of the circadian period
      length modulator, glycogen synthase kinase-3 beta (GSK3beta), in the SCN of
      synRas mice. Conversely, downregulation of Ras activity by blocking its function
      with an antibody in oscillating cell cultures reduced protein levels and
      increased phosphorylation of GSK3beta and lengthened the period of BMAL1 promoter
      driven luciferase activity. Furthermore, enhanced Ras activity in synRas mice
      resulted in a potentiation of light-induced phase delays at early subjective
      night, and increased photic induction of pERK1,2/pCREB and c-Fos. In contrast, at
      late subjective night, photic activation of Ras/ERK1,2/CREB in synRas mice was
      not sufficient to stimulate c-Fos protein expression and phase advance the clock.
      Taken together, our results demonstrate that Ras activity fine tunes the period
      length and modulates photoentrainment of the circadian clock. 

PMID- 25762013
TI  - Antioxidant vitamin intake and mortality in three Central and Eastern European
      urban populations: the HAPIEE study.
AB  - PURPOSE: The aim of the study was to assess the relationships between individual
      level dietary intakes of antioxidant vitamins C, E and beta-carotene with all
      cause and cause-specific mortality in three Central and Eastern European (CEE)
      populations. METHODS: Data from the Health, Alcohol and Psychosocial factors in
      Eastern Europe cohort study were used. At the baseline survey, between 2002 and
      2005, 28,945 men and women aged 45-69 years were examined in Novosibirsk
      (Russia), Krakow (Poland) and seven Czech towns. Deaths in the cohorts were
      identified through mortality registers. Cox regression was used to estimate the
      association between vitamin consumption and all-cause, cardiovascular (CVD)
      disease and cancer mortality. RESULTS: In multivariable-adjusted analyses, there
      were no clear inverse associations between antioxidant vitamin intakes and
      mortality, although in some groups, several hazard ratios (HRs) were significant.
      For example, in men, compared with the lowest quintile of vitamin C intake, all
      cause mortality in the third and fourth quintiles was lower by 28 % (HR 0.72; 95
      % CI 0.61-0.85) and by 20 % (HR 0.80; 95 % CI 0.68-0.95), respectively. CVD
      mortality was lower by 35 % (HR 0.65; 95 % CI 0.50-0.84) and by 23 % (HR 0.77; 95
      % CI 0.59-0.99) in third and fourth quintile of vitamin C intake, respectively.
      In women, the third and fourth quintiles of dietary intake of vitamin E were
      associated with reduced risk of all-cause death by 33 % (HR 0.67; 95 % CI 0.53
      0.84) and by 23 % (HR 0.77; 95 % CI 0.61-0.97), respectively. Consumption of
      vitamin C, vitamin E and beta-carotene was not related to CVD mortality in women
      and to cancer mortality in either gender. CONCLUSION: This large prospective
      cohort study in CEE populations with low prevalence of vitamin supplementation
      did not find a strong, dose-response evidence for protective effects of
      antioxidant vitamin intake.

PMID- 25762015
TI  - Editorial comment: symposium: biologics and tissue healing in orthopaedics.

PMID- 25762014
TI  - Anterior and Anterolateral Approaches for THA Are Associated With Lower
      Dislocation Risk Without Higher Revision Risk.
AB  - BACKGROUND: Lack of consensus continues regarding the benefit of anteriorly based
      surgical approaches for primary total hip arthroplasty (THA). The purpose of this
      study was to evaluate the risk of aseptic revision, septic revision, and
      dislocations for various approaches used in primary THAs from a community-based
      healthcare organization. QUESTIONS/PURPOSES: (1) What is the incidence of aseptic
      revision, septic revision, and dislocation for primary THA in a large community
      based healthcare organization? (2) Does the risk of aseptic revision, septic
      revision, and dislocation vary by THA surgical approach? METHODS: The Kaiser
      Permanente Total Joint Replacement Registry was used to identify primary THAs
      performed between April 1, 2001 and December 31, 2011. Endpoints were septic
      revisions, aseptic revisions, and dislocations. The exposure of interest was
      surgical approach (posterior, anterolateral, direct lateral, direct anterior).
      Patient, implant, surgeon, and hospital factors were evaluated as possible
      confounders. Survival analysis was performed with marginal multivariate Cox
      models. Hazard ratios (HRs) and 95% confidence intervals (CIs) are reported. A
      total of 42,438 primary THAs were available for analysis of revision outcomes and
      22,237 for dislocation. Median followup was 3 years (interquartile range, 1-5
      years). The registry's voluntary participation is 95%. The most commonly used
      approach was posterior (75%, N = 31,747) followed by anterolateral (10%, N =
      4226), direct anterior (4%, N = 1851), and direct lateral (2%, N = 667). RESULTS:
      During the study period 785 hips (2%) were revised for aseptic reasons, 213
      (0.5%) for septic reasons, and 276 (1%) experienced a dislocation. The revision
      rate per 100 years of observation was 0.54 for aseptic revisions, 0.15 for septic
      revisions, and 0.58 for dislocations. There were no differences in adjusted risk
      of revision (either septic or aseptic) across the different THA approaches.
      However, the anterolateral approach (adjusted HR, 0.29; 95% CI, 0.13-0.63, p =
      0.002) and direct anterior approach (adjusted HR, 0.44; 95% CI, 0.22-0.87, p =
      0.017) had a lower risk of dislocation relative to the posterior approach. There
      were no differences in any of the outcomes when comparing the direct anterior
      approach with the anterolateral approach. CONCLUSIONS: Anterior and anterolateral
      surgical approaches had the advantage of a lower risk of dislocation without
      increasing the risk of early revision. LEVEL OF EVIDENCE: Level III, therapeutic
      study.

PMID- 25762012
TI  - GM1 Ganglioside: Past Studies and Future Potential.
AB  - Gangliosides (sialic acid-containing glycosphingolipids) are abundant in neurons
      of all animal species and play important roles in many cell physiological
      processes, including differentiation, memory control, cell signaling, neuronal
      protection, neuronal recovery, and apoptosis. Gangliosides also function as
      anchors or entry points for various toxins, bacteria, viruses, and
      autoantibodies. GM1, a ganglioside component of mammalian brains, is present
      mainly in neurons. GM1 is one of the best studied gangliosides, and our
      understanding of its properties is extensive. Simple and rapid procedures are
      available for preparation of GM1 as a natural compound on a large scale, or as a
      derivative containing an isotopic radionuclide or a specific probe. Great
      research interest in the properties of GM1 arose from the discovery in the early
      1970s of its role as receptor for the bacterial toxin responsible for cholera
      pathogenesis. 

PMID- 25762016
TI  - Is There a Benefit to Highly Crosslinked Polyethylene in Posterior-stabilized
      Total Knee Arthroplasty? A Randomized Trial.
AB  - BACKGROUND: Polyethylene wear and osteolysis remain a concern with the use of
      modular, fixed-bearing total knee arthroplasty (TKA). A variety of highly
      crosslinked polyethylenes (XLPs) have been introduced to address this problem,
      but there are few data on the results and complications of this polyethylene in
      posterior-stabilized knee prostheses. QUESTIONS/PURPOSES: In a randomized
      prospective study design comparing standard polyethylene (SP) tibial inserts with
      XLP inserts, we asked the following questions: (1) Are there any differences in
      the clinical results (as measured by the classic Knee Society scoring system) and
      radiographic results (as measured by an evaluation for radiolucencies and
      osteolysis) between these groups? (2) What is the frequency of reoperation in
      these two groups? (3) Are there any specific complications related to XLP liners?
      METHODS: These are preliminary data from a single surgeon of a planned interim
      analysis of a prospective randomized study of one modular posterior-stabilized
      TKA. One hundred ninety-two patients (236 knees) were randomized to receive a SP
      compression-molded liner or a XLP (6.5 CGy electron beam-irradiated and remelted)
      polyethylene liner. There was no difference in the number of knees who were lost
      or refused followup (14 knees [13%] with XLP and 21 knees [17%] with SP).
      Patients were evaluated clinically using the original Knee Society scores, Lower
      Extremity Activity Score (LEAS), presence of knee effusion, and by standard
      radiographs for radiolucent lines and osteolytic lesions. This analysis was
      performed at a mean followup of 4.5 years (range, 2-8 years). RESULTS: There were
      no clinical differences between 99 knees with SP and 94 knees with XLP in
      original Knee Society total score (SP mean 95, SD 5; XLP mean 94, SD 7 [p =
      0.16]); change in total score (SP mean 41, 95% confidence interval [CI], 39-41;
      XLP mean 43, 95% CI, 39-48 [p = 0.56]); knee function score (SP mean 64 [SD 25];
      XLP mean 64 [SD 24] p = 0.98; change in function score (SP mean 22, 95% CI, 17
      27; XLP mean 21, 95% CI, 17-27 [p = 0.79]); LEAS score (both SP and XLP 9 [SD 2];
      p = 0.88); and change in LEAS (both SP and XLP mean 1, 95% CI, 1-2 [p = 0.0.38]).
      There were no differences, with the numbers available, in the presence of
      effusion (two of 94 XLP and five of 99 SP) with 2 years minimum followup. There
      were no differences in the frequency of radiolucent lines (13 knees with SP and
      15 with XLP) or of osteolysis (two knees with SP and none with XLP). There was no
      difference in frequency of reoperation between the two groups (three infections
      in 110 knees allocated to the XLP group and five (two infections, one femoral
      loosening, one instability, one fracture plating) in 122 knees allocated to the
      standard group. There were no complications related to the XLP liner.
      CONCLUSIONS: In this interim analysis, with the numbers available, there were no
      complications, but no advantages, related to the use of this XLP tibial liner.
      Additional enrollment has continued, and longer followup of these patients will
      be necessary to determine whether long-term wear characteristics differ between
      the groups. LEVEL OF EVIDENCE: Level I, therapeutic study.

PMID- 25762017
TI  - Do Rerevision Rates Differ After First-time Revision of Primary THA With a
      Cemented and Cementless Femoral Component?
AB  - BACKGROUND: Worldwide use of cementless fixation for total hip arthroplasty (THA)
      is on the rise despite some evidence from the world's registries suggesting
      inferior survivorship compared with cemented techniques. The patterns of bone
      loss associated with failed cementless and cemented THAs may prejudice the
      results of future revision procedures; however, this has not been documented.
      QUESTIONS/PURPOSES: The purpose of this study was to compare (1) the risk for
      rerevision of first revision THA; (2) the patterns of femoral bone loss at the
      time of first revision of primary THA; (3) the reasons for first revision of
      primary THA; and (4) the time to first revision of primary THA between primary
      cementless and cemented femoral components. METHODS: Primary THAs with cemented
      (n = 1791) and uncemented (n = 805) femoral components that subsequently
      sustained first revision of the femoral component were identified from the Danish
      Hip Arthroplasty Registry (DHR). As of 2012, 120,988 primary THAs and 19,282
      revisions were registered in the DHR with completeness of 97% and 90% for primary
      and revision THA, respectively. Median followup for revisions of primary THA with
      cemented and cementless femoral component was 4 years (range, 0-17 years) and 2
      years (range, 0-16 years), respectively. Survival of first revision THA, with
      second revision of the femur as outcome, was evaluated using hazard ratios (HRs)
      with 95% confidence interval (CI) adjusting for potential confounding. All
      patient- and surgery-related data are collected from Danish medical databases.
      Recording of bone defects in the DHR is based on surgeons' intraoperative
      findings. RESULTS: With the numbers studied, we found no differences in the risk
      of second revision between the overall cohort between cementless and cemented
      techniques (HR, 1.32; 95% CI, 0.97-1.80; p = 0.076); however, a second revision
      for any reason was more likely in patients < 70 years old in whom the index
      arthroplasty was performed using a cementless technique (HR, 1.48; 95% CI, 1.01
      2.17; p = 0.046). Increasingly severe femoral bone defects of type II (30% [532
      of 1791] versus 13% [104 of 805]; p < 0.001) type III (11% [200 of 1791] versus
      2% [12 of 805]; p < 0.001) and type IV (1% [26 of 1791] versus 0.4% [three of
      805]; p = 0.016) were more frequent at revisions of cemented femoral components
      compared with cementless femoral components. Indications for first revision
      differed between primary cemented and uncemented femoral components, because a
      larger proportion of cemented femoral components was revised as a result of
      aseptic loosening compared with cementless femoral components (74% [1329 of 1791]
      versus 25% [197 of 805]; p < 0.001), whereas a larger proportion of cementless
      femoral components was revised as a result of a fracture compared with cemented
      femoral components (46% [371 of 805] versus 10% [168 of 1791]; p < 0.001).
      Failure before 5 years was more likely in cementless femoral components than
      cemented femoral components (91% [733 of 805] versus 44% [749 of 1791], p <
      0.001). CONCLUSIONS: We found no differences in the risk of second revision in
      the overall cohort between cementless and cemented techniques; however, we
      observed an increased risk for rerevision THA performed on patients < 70 years
      whose index THAs were performed using cementless components when looking at all
      causes for revision, even after adjusting for the most likely confounding
      factors. Our data suggest that increased use of cementless fixation in primary
      THA may lead to inferior survivorship of first revision THA. LEVEL OF EVIDENCE:
      Level III, therapeutic study.

PMID- 25762018
TI  - Do Sex Differences Exist in Rates of Falls and Fractures in Hutterite, Rural, and
      Nonrural Populations, Aged 20 to 66 Years?
AB  - BACKGROUND: Falls and fractures are a major public health concern with an
      economic impact of more than USD 19 billion per year. Extensive research into the
      risk of falls and fractures in elderly populations has been performed; however,
      little is known about fall or fracture risk in younger populations. Additionally,
      sex- and population-specific (rural versus nonrural) fall and fracture risk may
      be important in identifying groups most at risk in an effort to develop
      preventive measures. QUESTIONS/PURPOSES: The purpose of this study was to
      determine whether sex and population (rural versus nonrural) differences exist in
      fall and fracture rates. METHODS: Data from 1256 (538 men) participants of the
      South Dakota Rural Bone Health Study, a population-based cohort study, including
      those living a rural lifestyle (n=349 non-Hutterites and 572 Hutterites) and a
      nonrural lifestyle (n=335), were used to address our a priori hypotheses. Health
      histories, physical activity recall, anthropometric measurements, and dual-energy
      xray absorptiometry measurements of body composition were obtained longitudinally
      from participants every 18 months for 7.5 years. Falls and fractures were self
      reported and fractures were confirmed through medical record review. Incidence
      rates were calculated as the number of falls or fractures per 1000 person-years
      and generalized estimating equations determined the association of sex and
      population group with fall and fractures rates while accounting for the repeated
      longitudinal measurements on the same person. All models adjusted for age group,
      percent time in moderate and vigorous physical activity, lean and fat mass, grip
      strength, and previous diagnosis of osteoarthritis. RESULTS: Males aged 39 years
      and younger had a 135% greater fall risk than females in the same age category
      (p=0.03), but there was no differences between males and females 40 years of age
      or older (p=0.26; age-by-sex interaction, p=0.05). No sex differences were
      observed for fracture risk. After controlling for covariates, rural and nonrural
      individuals fell at higher rates than Hutterites (84% and 50%, respectively,
      p<0.001). Additionally, rural individuals fractured at a 72% greater rate than
      Hutterites after controlling for covariates (p=0.03). CONCLUSIONS: Sex
      differences in fall risk among younger individuals along with population
      differences in fall and fracture rates suggest that sex and lifestyle factors may
      have an impact on fall and fracture risk. Future studies focusing on sex- and
      population-specific risk factors are necessary to develop prevention strategies
      tailored to specific populations. LEVEL OF EVIDENCE: Level III, prospective
      study.

PMID- 25762019
TI  - Comprehensive analysis of polymorphisms in the HLA-G 5' upstream regulatory and
      3' untranslated regions in Brazilian patients with systemic lupus erythematosus.
AB  - This study aims to comprehensively analyze human leucocyte antigen (HLA)-G
      polymorphisms association with susceptibility to systemic lupus erythematosus
      (SLE) development and clinical manifestations. The HLA-G 5' upstream regulatory
      region (URR), 3' untranslated region (UTR) and a cytosine deletion at exon 3
      (DeltaC, HLA-G*0105N allele) were analyzed in 114 SLE patients and 128 healthy
      controls from North East Brazil. The +3003T>C (rs1707) C allele and the HG010101c
      extended HLA-G allele were significantly more frequent in SLE patients than
      healthy controls (+3003C allele frequency: 12% in SLE patients vs 6% in controls;
      odds ratio (OR), 2.10, 95% confidence interval (CI), 1.06-4.28, P = 0.026;
      HG010101c frequency: 11.8% in SLE patients and 6.3% in controls; OR, 2.14, 95%
      CI, 1.01-4.51, P = 0.046) and were associated with susceptibility for disease
      development. Other polymorphisms were associated with different clinical
      manifestations. Although HLA-G role in SLE disease is far from being elucidated
      yet, our association study results along with a systematic review and meta
      analysis suggest that HLA-G might be able to slightly modulate the complex SLE
      phenotype (pooled OR, 1.14, 95% CI, 1.02-1.27, P = 0.021). 

PMID- 25762020
TI  - MRM as a discovery tool?
AB  - Multiple-reaction monitoring (MRM) of peptides has been recognized as a promising
      technology because it is sensitive and robust. Borrowed from stable-isotope
      dilution (SID) methodologies in the field of small molecules, MRM is now
      routinely used in proteomics laboratories. While its usefulness validating
      candidate targets is widely accepted, it has not been established as a discovery
      tool. Traditional thinking has been that MRM workflows cannot be multiplexed high
      enough to efficiently profile. This is due to slower instrument scan rates and
      the complexities of developing increasingly large scheduling methods. In this
      issue, Colangelo et al. (Proteomics 2015, 15, 1202-1214) describe a pipeline
      (xMRM) for discovery-style MRM using label-free methods (i.e. relative
      quantitation). Label-free comes with cost benefits as does MRM, where data are
      easier to analyze than full-scan. Their paper offers numerous improvements in
      method design and data analysis. The robustness of their pipeline was tested on
      rodent postsynaptic density fractions. There, they were able to accurately
      quantify 112 proteins at a CV% of 11.4, with only 2.5% of the 1697 transitions
      requiring user intervention. Colangelo et al. aim to extend the reach of MRM
      deeper into the realm of discovery proteomics, an area that is currently
      dominated by data-dependent and data-independent workflows. 

PMID- 25762021
TI  - Response to ELF cut-off points: aetiology is also a relevant factor.

PMID- 25762022
TI  - Bioreactor process parameter screening utilizing a Plackett-Burman design for a
      model monoclonal antibody.
AB  - Consistent high-quality antibody yield is a key goal for cell culture
      bioprocessing. This endpoint is typically achieved in commercial settings through
      product and process engineering of bioreactor parameters during development. When
      the process is complex and not optimized, small changes in composition and
      control may yield a finished product of less desirable quality. Therefore,
      changes proposed to currently validated processes usually require justification
      and are reported to the US FDA for approval. Recently, design-of-experiments
      based approaches have been explored to rapidly and efficiently achieve this goal
      of optimized yield with a better understanding of product and process variables
      that affect a product's critical quality attributes. Here, we present a
      laboratory-scale model culture where we apply a Plackett-Burman screening design
      to parallel cultures to study the main effects of 11 process variables. This
      exercise allowed us to determine the relative importance of these variables and
      identify the most important factors to be further optimized in order to control
      both desirable and undesirable glycan profiles. We found engineering changes
      relating to culture temperature and nonessential amino acid supplementation
      significantly impacted glycan profiles associated with fucosylation, beta
      galactosylation, and sialylation. All of these are important for monoclonal
      antibody product quality.

PMID- 25762023
TI  - CINPA1 is an inhibitor of constitutive androstane receptor that does not activate
      pregnane X receptor.
AB  - Constitutive androstane receptor (CAR) and pregnane X receptor (PXR) are
      xenobiotic sensors that enhance the detoxification and elimination of xenobiotics
      and endobiotics by modulating the expression of genes encoding drug-metabolizing
      enzymes and transporters. Elevated levels of drug-metabolizing enzymes and efflux
      transporters, resulting from CAR activation in various cancers, promote the
      elimination of chemotherapeutic agents, leading to reduced therapeutic
      effectiveness and acquired drug resistance. CAR inhibitors, in combination with
      existing chemotherapeutics, could therefore be used to attenuate multidrug
      resistance in cancers. Interestingly, all previously reported CAR inverse
      agonists are also activators of PXR, rendering them mechanistically
      counterproductive in tissues where both these xenobiotic receptors are present
      and active. We used a directed high-throughput screening approach, followed by
      subsequent mechanistic studies, to identify novel, potent, and specific small
      molecule CAR inhibitors that do not activate PXR. We describe here one such
      inhibitor, CINPA1 (CAR inhibitor not PXR activator 1), capable of reducing CAR
      mediated transcription with an IC50 of ~70 nM. CINPA1 1) is a specific xenobiotic
      receptor inhibitor and has no cytotoxic effects up to 30 uM; 2) inhibits CAR
      mediated gene expression in primary human hepatocytes, where CAR is endogenously
      expressed; 3) does not alter the protein levels or subcellular localization of
      CAR; 4) increases corepressor and reduces coactivator interaction with the CAR
      ligand-binding domain in mammalian two-hybrid assays; and 5) disrupts CAR binding
      to the promoter regions of target genes in chromatin immunoprecipitation assays.
      CINPA1 could be used as a novel molecular tool for understanding CAR function. 

PMID- 25762025
TI  - FTY720 Phosphate Activates Sphingosine-1-Phosphate Receptor 2 and Selectively
      Couples to Galpha12/13/Rho/ROCK to Induce Myofibroblast Contraction.
AB  - FTY720 phosphate (FTY720-P; 2-amino-2-[2-(4-octylphenyl)ethyl]-1,3-propanediol,
      monodihydrogen phosphate ester) is a nonselective sphingosine-1-phosphate (S1P)
      receptor agonist thought to be devoid of activity at the S1P2 receptor subtype.
      However, we have recently shown that FTY720-P displays significant S1P2 receptor
      agonist activity in recombinant cells and fibroblasts expressing endogenous S1P2
      receptors. To elucidate the S1P2-dependent signaling pathways that were activated
      by FTY720-P, we employed second messenger assays and impedance-based assays in
      combination with pharmacological and small interfering RNA-based pathway
      inhibition in recombinant Chinese hamster ovary (CHO)-S1P2 cells as well as human
      lung myofibroblasts generated in vitro. In CHO-S1P2 cells, FTY720-P did not
      modulate cAMP or calcium levels. However, reporter-gene assays, impedance-based
      assays with a selective Rho-associated kinase (ROCK) inhibitor, Galpha12/13
      knockdown and activated Rho-pull-down assays demonstrated that FTY720-P potently
      activated Galpha12/13/Rho/ROCK signaling. S1P similarly activated
      Galpha12/13/Rho/ROCK signaling via S1P2 receptors, whereas the two selective S1P1
      receptor agonists (Z,Z)-5-(3-chloro-4-[(2R)-2,3-dihydroxy-propoxy]-benzylidene)-2
      propylimino-3-o-tolyl-thiazolidin-4-one (ponesimond) and 5-[4-phenyl-5
      (trifluoromethyl)thiophen-2-yl]-3-[3-(trifluoromethyl)phenyl]1,2,4-oxadiazole
      (SEW2871) were inactive. In lung myofibroblasts, which mainly expressed the S1P2
      receptor subtype, we showed that FTY720-P selectively activated the
      Galpha12/13/Rho/ROCK pathway via the S1P2 receptor. Moreover, the activation of
      the Galpha12/13/Rho/ROCK pathway in myofibroblasts by FTY720-P caused potent
      myofibroblast contraction similar to that induced by the natural ligand S1P.
      Thus, complementing second messenger assays with unbiased label-free assays or
      phenotypic assays in native expression systems can uncover activation of
      additional pathways, such as Galpha12/13/Rho/ROCK signaling. 

PMID- 25762024
TI  - Molecular Determinants of CGS21680 Binding to the Human Adenosine A2A Receptor.
AB  - The adenosine A2A receptor (A(2A)R) plays a key role in transmembrane signaling
      mediated by the endogenous agonist adenosine. Here, we describe the crystal
      structure of human A2AR thermostabilized in an active-like conformation bound to
      the selective agonist 2-[p-(2-carboxyethyl)phenylethyl-amino]-5'-N
      ethylcarboxamido adenosine (CGS21680) at a resolution of 2.6 A. Comparison of
      A(2A)R structures bound to either CGS21680, 5'-N-ethylcarboxamido adenosine
      (NECA), UK432097 [6-(2,2-diphenylethylamino)-9-[(2R,3R,4S,5S)-5-(ethylcarbamoyl)
      3,4-dihydroxy-tetrahydrofuran-2-yl]-N-[2-[[1-(2-pyridyl)-4
      piperidyl]carbamoylamino]ethyl]purine-2-carboxamide], or adenosine shows that the
      adenosine moiety of the ligands binds to the receptor in an identical fashion.
      However, an extension in CGS21680 compared with adenosine, the (2
      carboxyethyl)phenylethylamino group, binds in an extended vestibule formed from
      transmembrane regions 2 and 7 (TM2 and TM7) and extracellular loops 2 and 3 (EL2
      and EL3). The (2-carboxyethyl)phenylethylamino group makes van der Waals contacts
      with side chains of amino acid residues Glu169(EL2), His264(EL3), Leu267(7.32),
      and Ile274(7.39), and the amine group forms a hydrogen bond with the side chain
      of Ser67(2.65). Of these residues, only Ile274(7.39) is absolutely conserved
      across the human adenosine receptor subfamily. The major difference between the
      structures of A(2A)R bound to either adenosine or CGS21680 is that the binding
      pocket narrows at the extracellular surface when CGS21680 is bound, due to an
      inward tilt of TM2 in that region. This conformation is stabilized by hydrogen
      bonds formed by the side chain of Ser67(2.65) to CGS21680, either directly or via
      an ordered water molecule. Mutation of amino acid residues Ser67(2.65),
      Glu169(EL2), and His264(EL3), and analysis of receptor activation either in the
      presence or absence of ligands implicates this region in modulating the level of
      basal activity of A(2A)R.

PMID- 25762028
TI  - Effects of posterior tympanotomy with steroids at round window on hearing
      recovery after revision surgery for intractable Meniere's disease.
AB  - CONCLUSIONS: At the second postoperative year, there were no significant
      differences between results for vertigo and hearing after endolymphatic sac
      drainage with steroid instillation surgery (EDSS) and EDSS with posterior
      tympanotomy with steroids at the round window (EDRW). In particular, as regards
      hearing recovery to the preoperative level, the periods after EDRW were shorter
      than those after the second EDSS. OBJECTIVES: Patients sometimes faces recurrent
      problems years after EDSS due to endolymphatic sac closure and/or disease
      progression. In the present study, we examined the effects of EDRW on vertigo and
      hearing after revision surgery for intractable relapsed Meniere's disease.
      METHODS: Sixteen patients with Meniere's disease had revision surgery due to
      intractable recurrence of disease, and were followed up regularly at least for 2
      years. As revision surgery, EDSS was performed repeated in eight cases and EDRW
      was performed in the other eight. There were no significant differences between
      the patients' backgrounds in the two groups. RESULTS: Periods of hearing recovery
      to the preoperative level were 11.5 +/- 4.4 months after the first EDSS, although
      it took 16.4 +/- 2.6 months longer after revision surgery with the second EDSS (p
      = 0.038 < 0.05: first EDSS vs second EDSS) and was 10.0 +/- 3.3 months shorter
      after revision surgery with EDRW (p = 0.010 < 0.05: second EDSS vs EDRW).

PMID- 25762026
TI  - Failure of introduction of food allergens after negative oral food challenge
      tests in children.
AB  - One of the purposes to perform an oral food challenge (FC) test is to avoid
      unnecessary elimination of food allergens. In case of a negative FC test result,
      the food can be introduced. It is, however, unknown if patients act according to
      the outcome of the test. This study evaluates the rate of introduction of peanut,
      hazelnut, cow's milk or hen's egg allergens after a negative FC test. We
      investigated the introduction rate of children (0-18 years) with a negative FC
      test visiting the Department of Allergology, Erasmus Medical Centre Rotterdam
      from 2008 till 2013 and the factors that influence the rate of introduction.
      Patients were asked to complete a comprehensive questionnaire about their FC
      test. In total, 157 (38% girls, mean age during challenge 6.9 years) participated
      in the study. Of these FC tests, 104 (56%) were followed by a successful
      introduction, 30 (16%) by a partly introduction (traces or processed foods) and
      52 (28%) by a failed introduction. Peanut and hazelnut showed a statistically
      significant lower successful introduction rate. Age, gender, symptoms during FC
      test, dietary advice and time period to introduction significantly influenced the
      rate of introduction. One fourth of the children with failure of introducing
      foods experienced symptoms during the introduction. CONCLUSION: More than one
      quarter of all children with a negative FC test result did not introduce the
      food. The FC test in its current form does not achieve its objective for this
      group of children.

PMID- 25762030
TI  - European guidance for the molecular diagnosis of pseudohypoparathyroidism not
      caused by point genetic variants at GNAS: an EQA study.

PMID- 25762031
TI  - EMQN Best Practice Guidelines for molecular and haematology methods for carrier
      identification and prenatal diagnosis of the haemoglobinopathies.

PMID- 25762027
TI  - Evaluation of 98 immunocompetent children with cytomegalovirus infection:
      importance of neurodevelopmental follow-up.
AB  - This study aims to analyze and evaluate the clinic and demographic features of
      immunocompetent children that have been diagnosed with cytomegalovirus (CMV)
      infection. The data of children diagnosed with CMV infection between January 2005
      and December 2010 and their follow-ups for 2 years were retrospectively
      evaluated. Ninety-eight patients were included, and the median age at admission
      was 5.6 months (5 days-36 months). 54.1% was male. The diagnosis of CMV infection
      was performed by measurement of serum anti-CMV specific Ig M and IgG titers and
      PCR method in blood and/or urine. In 3.06% of the patients, congenital infection
      was detected, whereas possible congenital infection was observed in 36.7% of the
      patients. Furthermore, 44 patients (44.8%) were detected to have perinatal
      infection while postnatal infection was spotted in 15.3% of the patients. The
      common presenting manifestations were prolonged jaundice, diarrhea, vomiting,
      abdominal distension, skin eruption, and seizure. And the most common physical
      examination findings were hepatosplenomegaly, microcephaly, jaundice, and
      petechia. The mainstream laboratory results were elevated transaminases (50%),
      anemia (30.6%), leukocytosis (27.5%), and thrombocytopenia (18.3%). There were
      intracranial calcification in 5.1% and eye findings in 5.1%. On follow-up of
      patients, complete improvement (59.1%), neuromotor developmental delay (11.2%),
      epilepsy (10.2%), hearing loss (3.06 %), hemolytic anemia (2.04%), and growth
      retardation (1.02%) were detected. CONCLUSION: CMV infection is a significant
      disease both in congenital and perinatal period. It must be considered that
      diagnosed patients need to be monitored for a long time with special attention to
      their neurodevelopmental follow-ups.

PMID- 25762032
TI  - Bilateral substrate effect on the thermal conductivity of two-dimensional
      silicon.
AB  - Silicene, the silicon-based counterpart of graphene, has received exceptional
      attention from a wide community of scientists and engineers in addition to
      graphene, due to its unique and fascinating physical and chemical properties.
      Recently, the thermal transport of the atomic thin Si layer, critical to various
      applications in nanoelectronics, has been studied; however, to date, the
      substrate effect has not been investigated. In this paper, we present our
      nonequilibrium molecular dynamics studies on the phonon transport of silicene
      supported on different substrates. A counter-intuitive phenomenon, in which the
      thermal conductivity of silicene can be either enhanced or suppressed by changing
      the surface crystal plane of the substrate, has been observed. This phenomenon is
      fundamentally different from the general understanding of supported graphene, a
      representative two-dimensional material, in which the substrate always has a
      negative effect on the phonon transport of graphene. By performing phonon
      polarization and spectral energy density analysis, we explain the underlying
      physics of the new phenomenon in terms of the different impacts on the dominant
      phonons in the thermal transport of silicene induced by the substrate: the
      dramatic increase in the thermal conductivity of silicene supported on the 6H-SiC
      substrate is due to the augmented lifetime of the majority of the acoustic
      phonons, while the significant decrease in the thermal conductivity of silicene
      supported on the 3C-SiC substrate results from the reduction in the lifetime of
      almost the entire phonon spectrum. Our results suggest that, by choosing
      different substrates, the thermal conductivity of silicene can be largely tuned,
      which paves the way for manipulating the thermal transport properties of silicene
      for future emerging applications. 

PMID- 25762033
TI  - Attenuation correction in cardiac PET: To raise awareness for a problem which is
      as old as PET/CT.

PMID- 25762034
TI  - Looking at the whole picture.

PMID- 25762035
TI  - False-positive (13)N-ammonia/(18)FDG PET for evaluation of cardiac sarcoidosis in
      a patient on peritoneal dialysis.

PMID- 25762036
TI  - Guest editorial.

PMID- 25762037
TI  - Dental demographics and metrics of oral diseases in the ageing Australian
      population.
AB  - One of the biggest challenges currently facing the dental profession in Australia
      is the provision of quality and timely dental care to the elderly. Adults aged
      65+ years are an exponentially growing section of the community with rapidly
      changing dental needs, thanks in part to improvements in oral health over the
      past 60 years that have resulted in a dramatically decreased rate of edentulism
      and subsequently an increased number of teeth present. This is a challenge not
      only for the public dental services, but also public health policy makers,
      private dental practitioners, professional organizations and dental education
      providers. It is an issue that crosses a range of dental care providers, not only
      dentists but also dental prosthetists and dental hygienists, whose role in the
      provision of dental services has been slowly growing in Australia. Furthermore,
      with evidence of links between oral and systemic health, this issue has
      significant impacts for the broader health system. 

PMID- 25762038
TI  - Periodontal considerations in older individuals.
AB  - In the next few years there will be a great increase in the percentage of the
      population aged over 65. Not only will they have more teeth than previous
      generations, but also a large number of implants. The increase in age is
      accompanied by an increase in the prevalence and incidence of periodontal
      diseases. In addition, there is a decrease in manual dexterity and an increase in
      co-morbidity and medications affecting the oral cavity. Dental care in aged care
      facilities can be poor and access to dental professionals difficult. This article
      discusses these issues. 

PMID- 25762039
TI  - Endodontics and the ageing patient.
AB  - Patients are living longer and the rate of edentulism is decreasing. Endodontic
      treatment is an essential part of maintaining the health and well-being of the
      elderly. Retention of natural teeth improves the quality of life and the overall
      health and longevity of ageing patients. Also, teeth that might be otherwise
      extracted may be strategically valuable to retain a prosthesis, and elderly
      patients are more likely to have medical complications that may prevent dental
      extractions from being safely performed. The technical goals of endodontic
      treatment in the elderly are the same as those for younger patients. However, the
      pulpo-dentinal complex undergoes calcific changes over time, which may pose
      challenges for the clinician. The purposes of this review are to discuss age
      changes in the pulp and the challenges posed by diagnosing, treatment planning
      and treating the elderly endodontic patient. 

PMID- 25762040
TI  - Implants for the ageing population.
AB  - Dental implant treatment has established benefits over traditional alternatives.
      Age-related changes in systemic and oral health in conjunction with social,
      economic and resource considerations often introduce complexities into dental
      implant treatment of ageing patients. When time, opportunity, discomfort and
      maintenance costs are coupled with cost-benefit and quality of life predictions,
      otherwise simple treatment decisions can become more difficult. Implants for
      different types of prostheses in both arches and the different types of
      prostheses themselves present a variety of treatment challenges, risks, benefits
      and maintenance requirements. This narrative review discusses selective
      literature pertinent to the provision of dental implant treatment in the ageing
      population. 

PMID- 25762041
TI  - Oral medicine and the ageing population.
AB  - The oral cavity is subject to age related processes such as cellular ageing and
      immunosenescence. The ageing population bears an increased burden of intraoral
      pathology. In oral medicine, the majority of presenting patients are in their
      fifth to seventh decade of life. In this review, we discuss the ageing
      population's susceptibility to mucosal disorders and the increased prevalence of
      potentially malignant disorders and oral squamous cell carcinoma, as well as
      dermatoses including oral lichen planus and immunobullous conditions. We also
      address the ageing population's susceptibility to oral discomfort and explore
      salivary secretion, ulceration and the symptoms of oral burning. Finally, we will
      describe orofacial pain conditions which are more likely encountered in an older
      population. This update highlights clinical presentations which are more likely
      to be encountered in the ageing population in a general practice setting and the
      importance of screening both new and long-term patients. 

PMID- 25762042
TI  - Dry mouth and older people.
AB  - Dry mouth is more common among older people than in any other age group.
      Appropriate definition and accurate measurement of dry mouth is critical for
      better understanding, monitoring and treatment of the condition. Xerostomia is
      the symptom(s) of dry mouth; it can be measured using methods ranging from single
      questions to multi-item summated rating scales. Low salivary flow (known as
      salivary gland hypofunction, or SGH) must be determined by measuring that flow.
      The relationship between SGH and xerostomia is not straightforward, but both
      conditions are common among older people, and they affect sufferers' day-to-day
      lives in important ways. The major risk factor for dry mouth is the taking of
      particular medications, and older people take more of those than any other age
      group, not only for symptomatic relief of various age-associated chronic
      diseases, but also in order to reduce the likelihood of complications which may
      arise from those conditions. The greater the number taken, the greater the
      associated anticholinergic burden, and the more likely it is that the individual
      will suffer from dry mouth. Since treating dry mouth is such a challenge for
      clinicians, there is a need for dentists, doctors and pharmacists to work
      together to prevent it occurring. 

PMID- 25762043
TI  - Medico-legal aspects of dental treatment of the ageing and aged patient.
AB  - The medico-legal aspects of the dental management of ageing and aged patients
      relate mainly to the assessment of the patient's competence and the role of
      substitute decision makers. Dentists will assess whether or not a patient is
      competent to give informed consent to treatment. Lawyers use the word 'capacity'
      when deciding whether a person can make an important decision about their life.
      Competence and capacity mean the same thing. Assessment of competence and the
      role of substitute decision makers rests firmly on a sound understanding of the
      ethical basis of dental practice. This article will discuss the ethical basis of
      dental practice; the assessment of competence and the gaining of informed
      consent; the role of substitute decision makers and the nature of the decisions
      that are made at the end of life. 

PMID- 25762045
TI  - Ageing, dementia and oral health.
AB  - Neurocognitive decline and delirium, frailty, incontinence, falls, hearing and
      vision impairment, medication compliance and pharmacokinetics, skin breakdown,
      impaired sleep and rest are regarded as geriatric giants by gerontologists,
      geriatricians and nursing home staff. As these are all interrelated in the
      elderly, failure to act on one can impact on the others. However, the
      implications of poor oral health have for too long been ignored and deserve equal
      status. Mouth pain can be devastating for the elderly, compound psychosocial
      problems, frustrate carers and nursing home staff and disrupt family dynamics. As
      appearance, function and comfort suffer, so may a person's self-esteem and
      confidence. The contributing factors for poor oral health such as rapid dental
      decay, acute and chronic periodontal infections and compromised systemic health
      on a background of a dry mouth, coupled with xerostomia-inducing medications,
      reduced fine motor function, declining cognition and motivation will not only
      lead to an increase in both morbidity and mortality but also impact on quality of
      life. 

PMID- 25762044
TI  - Treatment planning concepts for the ageing patient.
AB  - There is an ageing imperative in Australia as in many other industrialized
      nations, and these populations are extremely heterogeneous. In young adults, the
      factors which influence decision making for oral health care are whether the
      patient has the will, the time or the finances to pay for care, while for
      clinicians, the decisions are whether they have the skill and the resources to
      carry out the treatment plan. For older adults, the decision making includes all
      of the previous identified factors, but they are now complicated by the patient's
      medical and medication problems, the side effects of the medications they are
      taking, their cognitive status as well as the cumulative effects of a lifetime of
      physiological, traumatic and iatrogenic effects on the dentition and the oral
      cavity. The decision-making process which has evolved has been called many names,
      from cost-effective care to minimal invasive dentistry to rational dental care.
      Fundamentally, they are similar. Rational dental care has been defined as the
      process of decision making, which develops a treatment plan that is in the best
      interest of the patient after evaluating all of the modifying factors. This
      article will discuss the various concepts, and the strengths and weaknesses of
      some of these systems. It will also illustrate some of the clinical problems as
      there is very little evidence-based data to support any of these concepts.
      However, treatment planning is still an art, which can only be carried out for an
      individual and not a group, and the result must serve the needs of the patient
      and enhance the quality of his or her life. 

PMID- 25762046
TI  - Improving the oral health of frail and functionally dependent elderly.
AB  - The Australian Government endorsed a national evidence based oral health model
      when it introduced the first Nursing Home Oral and Dental Health Plan in 2010.
      Called Better Oral Health in Residential Care, it promotes a multidisciplinary
      approach with doctors, nurses, care workers and dental professionals sharing
      responsibility for the four key processes of oral health screening, oral health
      care planning, daily oral hygiene and access to dental treatment. Frail and
      dependent residents are most conveniently treated on-site, hence an aged
      care/dental partnership is encouraged to facilitate the use of portable dental
      equipment in the delivery of dental care. Currently, few dentists provide
      services to residential aged care facilities (RACFs), with loss of clinical time
      in practice, difficulty in providing clinical care in a non-dental environment
      and lack of referral pathways from the RACFs to the dentists contributing to the
      problem. The need to establish a model of care involving dental hygienists/oral
      health therapists in RACFs has merit. Minimal intervention treatment using glass
      ionomer cement (GIC) and silver fluoride is ideal in aged care. However, GIC has
      limitation in dry mouths with low pH caused by polypharmacy or disease.
      Palliative and definitive treatment techniques need to be individualized with
      consideration of a patient's ability to maintain their own mouths as well as
      their mental and physical competence. The range of products available to address
      the oral diseases common to the frail elderly is growing. The oral health care
      provider is required to establish a preventive regime that is tailored to the
      patient's needs, is realistic and under revision as the patient's needs change. 

PMID- 25762047
TI  - Advanced restorative dentistry - a problem for the elderly? An ethical dilemma.
AB  - The type of dental restorations taken into old age may have an adverse effect on
      the quality of life of the elderly. Root caries and dry mouth increase in
      prevalence with age and may precipitate the breakdown of remaining natural and
      restored teeth. At present the availability of dental personnel and facilities in
      residential aged care facilities (RACFs) is limited, often non-existent, and the
      elderly living at home may be unable to easily gain access to dental care. Thus,
      the provision of appropriate and timely dental treatment may not occur, resulting
      in prolonged pain and suffering. It is important that, as our elderly population
      increasingly retain natural teeth into advanced old age, appropriate funds are
      made available to ensure their dental health is maintained. A lack of early
      intervention to arrest dental disease may result in life-threatening medical
      consequences in the elderly, such as ventilator assisted pneumonia or the need
      for a general anaesthetic and possible associated medical risks. Significant
      local disease, such as osteonecrosis, may also result from a lack of appropriate
      dental intervention. The necessity to remove questionable teeth prior to
      irradiation for neoplastic disease or bisphosphonate prescription for neoplastic
      disease or severe osteoporosis emphasizes the need for regular dental care. In
      contrast, extensive dental restorative treatment for younger people may have
      benefits, such as optimal dental aesthetics and oral function, but in older
      individuals careful consideration should be given to select the most appropriate
      treatment modality so that adverse situations can be avoided or their resolution
      simplified should they occur later when the individual is compromised or in a
      RACF. This may mean the use of conservative dental restorative materials and an
      avoidance of complex restorative options which may be difficult for the
      individual or RACF staff to maintain. Some years after receipt of their complex
      restorations they may be unable to cope with the operative demands and financial
      burden of resolving their deteriorating dental situation and so complex implant
      born structures and precision removable prostheses should probably be avoided for
      those individuals contemplating entering a care situation. Therefore, the timing
      of the provision of complex dentistry poses an ethical dilemma. 

PMID- 25762048
TI  - Social implications and workforce issues in the oral health of an ageing
      population.
AB  - A functional and socially acceptable level of oral health is an integral part of
      healthy ageing! More teeth, more sophisticated dental technology and increasing
      co-morbidities of an ageing Australian society will have significant impacts on
      oral health professionals and their capacities to work within expanded teams of
      health, education and social organizations. Society is adapting its perspective
      on the social role of older citizens; replacing its perception of the elderly as
      an economic social burden, to one of senior citizens as being a respected and
      active source of social and economic benefit. Maintaining general and oral health
      for older Australians will bring into sharp focus the need for recognizing and
      managing not only the biological markers associated with ageing and frailty, but
      also the potential mediators on health outcomes associated with changing health
      and social behaviours. Increasing social capital of older Australians through
      national policy initiatives such as the Living Longer Living Better reforms, and
      greater involvement of allied health and carers' organizations in oral health
      education and health promotion will set a new scene for the roles of dental
      professionals. Issues of equity will drive the service delivery agenda, and a
      socio-cultural shift to 'consumer-directed' health outcomes will shape the range
      of services, quality of care and support required by an older Australian
      population. Formal education and training modules for aged care workers, allied
      health practitioners and geriatricians will develop. The challenge for the dental
      profession is the coordination and integration of these changes into new models
      of dental and general health care. 

PMID- 25762049
TI  - Geriatric dentistry, teaching and future directions.
AB  - BACKGROUND: Many nations are facing a demographic shift in the age profile of
      their population, leading the World Health Organization to a 'Call for Public
      Health Action' on the oral health of older people. METHODS: A search of the
      literature relevant to geriatric dentistry teaching was undertaken using MEDLINE,
      Web of Science, Eric and Psychlit. A search of dental professional school
      websites in Australia and policy and international practice documents was
      undertaken. RESULTS: The international literature describes requirements for
      geriatric dentistry courses and various approaches to teaching, including
      didactic teaching, practical experiences and external placements. Challenges are
      identified in the area of geriatric dental education. Educational institutions
      (with others) have an obligation to lead change, yet there appears to be little
      formal recognition in Australian dental curricula of the need to develop quality
      education and research programmes in geriatric dentistry. CONCLUSIONS:
      Internationally, the inclusion of geriatrics within dental curricula has been the
      subject of consideration since the 1970s. The current evidence indicates that
      geriatrics/gerodontology is not a significant component of dental curricula.
      Given the projected age distribution in many countries, the need for
      implementation of dental curriculum content in the area of
      geriatrics/gerodontology is evident.

PMID- 25762050
TI  - Cultural aspects of ageing and health promotion.
AB  - The emphasis of Australian Government policy is on the promotion of good health
      in later life and positive experiences with ageing. Conceptually, a new
      gerontology framework has replaced the study of disease, decline, loss and
      disability. Within this framework, health promotion offers a mechanism by which
      individuals can be assisted to create environments that offer better
      opportunities for continued participation in society and improved quality of
      health and self-care. Oral health is instrumental to older people's health, life
      satisfaction, quality of life and perception of self. Australia is culturally
      diverse, composed of numerous ethno-cultural groups coexisting within a larger,
      predominant culture, creating a multicultural and multiracial society. However,
      despite this cultural diversity, the well documented ageing profile of the
      Australian population and repeated calls for comprehensive geriatric assessment,
      the oral health of older adults remains a challenge for oral health providers and
      for society. A major challenge will be to translate existing knowledge and
      experience of disease prevention and health promotion into appropriate programmes
      for older adults. Health promotion is the key to improving oral health in later
      life as it encourages older adults to be proactive in regard to their health.
      Therefore, increased efforts should be directed towards identifying opportunities
      for health promotion activities and the development of community based models
      that encourage older people to improve and maintain their oral health. Ignoring
      opportunities for health promotion may increase inequalities in oral health and
      may lead to even greater demands for curative and oral rehabilitative services
      from these groups This article firstly provides a brief rationale for oral health
      promotion. Its second part explores the influence of culture on health beliefs,
      behaviours and outcomes in older adults and how oral health can relate to
      cultural background. The last section presents the results of an oral health
      promotion programme for older adults. 

PMID- 25762052
TI  - Comparison of local reactions to oxaliplatin infusions by peripheral versus
      central venous administration.
AB  - PURPOSE: Oxaliplatin, a platinum-type alkylator, is not classified as a vesicant
      but can cause local reactions when infused by peripheral vein. Providence Cancer
      Center, like other institutions, deferred the venous administration method to
      clinical judgment incorporating patient preference. Patient experience was
      evaluated for oxaliplatin-related local reactions by peripheral or central venous
      administration. METHODS: A retrospective review of the electronic medical record
      was performed of the period of January 2011 to March 2013 to identify patients
      who received oxaliplatin. Included were 59 patients who were given the option of
      either peripheral or central venous drug administration. The two patient groups
      (peripheral vein vs. central vein administration) were compared in terms of
      frequency and type of local reactions (redness/discoloration, swelling,
      numbness/cold, or pain/discomfort). RESULTS: Nineteen (63.3%) of the patients in
      the peripheral vein group experienced some type of local reaction compared to
      none in the central vein group (p < .0001). Pain was the most common local
      reaction, occurring in 17 (56.7%) patients in the peripheral group. Despite the
      occurrence of a local reaction, the majority of patients did not alter their
      initial choice of infusion method. CONCLUSION: This is the first published report
      to characterize and quantify a single institution's experience with oxaliplatin
      related local reactions. A significantly greater number of local reactions,
      particularly pain, occurred with the administration of oxaliplatin peripherally
      vs. centrally. This analysis impacted our institution's best practice for
      oxaliplatin infusions.

PMID- 25762053
TI  - Effects of the strain background and autolysis process on the composition and
      biophysical properties of the cell wall from two different industrial yeasts.
AB  - The Saccharomyces cerevisiae cell surface is endowed with some relevant
      technological properties, notably antimicrobial and biosorption activities. For
      these purposes, yeasts are usually processed and packaged in an 'autolysed/dried'
      formula, which may have some impacts on cell surface properties. In this report,
      we showed using a combination of biochemical, biophysical and molecular methods
      that the composition of the cell wall of two wine yeast strains was not altered
      by the autolysis process. In contrast, this process altered the nanomechanical
      properties as shown by a 2- to 4-fold increased surface roughness and to a higher
      adhesion to the atomic force microscope tips of the autolysed cells as compared
      to live yeast cells. Besides, we found that the two strains harboured differences
      in biomechanical properties that could be due in part to higher levels of mannan
      in one of them, and to the fact that the surface of this mannan-enriched strain
      is decorated with highly adhesive patches forming nanodomains. The presence of
      these nanodomains could be correlated with the upregulation of flocculin encoding
      FLO11 as well as to higher expression of few other genes encoding cell wall
      mannoproteins in this mannan-enriched strain as compared to the other strain. 

PMID- 25762051
TI  - Cadmium toxicity affects chlorophyll a and b content, antioxidant enzyme
      activities and mineral nutrient accumulation in strawberry.
AB  - BACKGROUND: Cadmium (Cd) is well known as one of the most toxic metals affecting
      the environment and can severely restrict plant growth and development. In this
      study, Cd toxicities were studied in strawberry cv. Camarosa using pot
      experiment. Chlorophyll and malondialdehyde (MDA) contents, catalase (CAT),
      superoxide dismutase (SOD), ascorbate peroxidase (APX) activities and mineral
      nutrient concentrations were investigated in both roots and leaves of strawberry
      plant after exposure Cd. RESULTS: Cd content in both roots and leaves was
      increased with the application of increasing concentrations of Cd. We found
      higher Cd concentration in roots rather than in leaves. Chlorophyll a and b was
      decreased in leaves but MDA significantly increased under increased Cd
      concentration treatments in both roots and leaves. SOD and CAT activities was
      also increased with the increase Cd concentrations. K, Mn and Mg concentrations
      were found higher in leaves than roots under Cd stress. In general, increased Cd
      treatments increased K, Mg, Fe, Ca, Cu and Zn concentration in both roots and
      leaves. Excessive Cd treatments reduced chlorophyll contents, increased
      antioxidant enzyme activities and changes in plant nutrition concentrations in
      both roots and leaves. CONCLUSION: The results presented in this work suggested
      that Cd treatments have negative effect on chlorophyll content and nearly
      decreased 30% of plant growth in strawberry. Strawberry roots accumulated higher
      Cd than leaves. We found that MDA and antioxidant enzyme (CAT, SOD and APX)
      contents may have considered a good indicator in determining Cd tolerance in
      strawberry plant.

PMID- 25762054
TI  - Incidence of percutaneous injury in Taiwan healthcare workers.
AB  - Reporting of percutaneous injuries (PIs) to the Chinese Exposure Prevention
      Information Network (EPINet) became mandatory for all public and tertiary
      referral hospitals in Taiwan in 2011. We have estimated the number of microbially
      contaminated PIs and the national PI incidence using a retrospective secondary
      data analysis approach to analyse 2011 data from the Chinese EPINet to determine
      the types of PI, mechanisms of occurrence and associated risks. The results
      revealed a national estimate of PIs between 6710 and 8319 in 2011. The most
      common incidents for physicians were disposable syringes, suture needles, and
      disposable scalpels; while for nurses they were disposable syringes, intravenous
      catheters, and lancets. About 13.0% of the source patients were seropositive for
      hepatitis B virus (HBV) surface antigen, 13.8% were seropositive for hepatitis C
      virus (HCV), and 1.1% seropositive for human immunodeficiency virus (HIV). From
      these results we estimate that annually 970 full-time healthcare workers (HCWs)
      would be exposed to HBV, 1094 to HCV, and 99 to HIV. This study improves our
      understanding of the mechanisms and risks of PIs and informs the development of
      more efficient preventive measures to protect HCWs from such injuries. 

PMID- 25762055
TI  - Closing the divide: the Harvard Global Equity Initiative-Lancet Commission on
      global access to pain control and palliative care.

PMID- 25762056
TI  - Oesophagus perforation mimicking an acute chest pain syndrome.

PMID- 25762057
TI  - Comparison between two types of confocal laser endomicroscopy in gastrointestinal
      tract.
AB  - OBJECTIVES: Confocal laser endomicroscopy (CLE) consists of endoscope-based CLE
      (eCLE) and probe-based CLE (pCLE). This study aimed to compare eCLE and pCLE in
      their diagnostic yield in different parts of the gastrointestinal (GI) tract.
      METHODS: Consecutive patients were scheduled for CLE examination due to GI
      symptoms. All patients were randomly assigned to eCLE or pCLE group and underwent
      a programmed procedure using one type of CLE. Differences in procedure time,
      complication rate, CLE image quality and image acquisition feasibility between
      these two types of CLE for esophagogastroduodenoscopy (EGD) and colonoscopy were
      calculated. RESULTS: Altogether 513 CLE procedures were performed, including 324
      EGD and 189 colonoscopy. The procedure time of pCLE was significantly shorter
      than that of eCLE both in EGD and colonoscopy (16.78 min vs 18.13 min for EGD, P
      = 0.027; 32.48 min vs 39.89 min for colonoscopy, P < 0.001). No significant
      difference was found between these two types of CLE in diagnostic utility,
      including the detection and prediction of histopathological results of the
      lesions. The CLE image quality of both eCLE and pCLE were comparable in the
      stomach and colon, but eCLE seemed to be superior to pCLE in examining the
      esophagus. Colonoscopy using pCLE had a higher complete rate than that of eCLE,
      although the difference was not statistically significant (P = 0.065).
      CONCLUSIONS: pCLE is more flexible in diagnosing GI diseases with a shorter
      procedure time than eCLE regardless of comparable diagnostic yields, except the
      diagnosis of esophageal diseases in which eCLE provides better image quality.

PMID- 25762058
TI  - A case of congenital complete absence of the pericardium.

PMID- 25762059
TI  - Coming of Age--CC Chemokine Ligand 18 in ANCA-Associated Vasculitis.

PMID- 25762060
TI  - CC Chemokine Ligand 18 in ANCA-Associated Crescentic GN.
AB  - ANCA-associated vasculitis is the most frequent cause of crescentic GN. To define
      new molecular and/or cellular biomarkers of this disease in the kidney, we
      performed microarray analyses of renal biopsy samples from patients with ANCA
      associated crescentic GN. Expression profiles were correlated with clinical data
      in a prospective study of patients with renal ANCA disease. CC chemokine ligand
      18 (CCL18), acting through CC chemokine receptor 8 (CCR8) on mononuclear cells,
      was identified as the most upregulated chemotactic cytokine in patients with
      newly diagnosed ANCA-associated crescentic GN. Macrophages and myeloid dendritic
      cells in the kidney were detected as CCL18-producing cells. The density of
      CCL18(+) cells correlated with crescent formation, interstitial inflammation, and
      impairment of renal function. CCL18 protein levels were higher in sera of
      patients with renal ANCA disease compared with those in sera of patients with
      other forms of crescentic GN. CCL18 serum levels were higher in patients who
      suffered from ANCA-associated renal relapses compared with those in patients who
      remained in remission. Using a murine model of crescentic GN, we explored the
      effects of the CCL18 murine functional analog CCL8 and its receptor CCR8 on
      kidney function and morphology. Compared with wild-type mice, Ccr8(-/-) mice had
      significantly less infiltration of pathogenic mononuclear phagocytes.
      Furthermore, Ccr8(-/-) mice maintained renal function better and had reduced
      renal tissue injury. In summary, our data indicate that CCL18 drives renal
      inflammation through CCR8-expressing cells and could serve as a biomarker for
      disease activity and renal relapse in ANCA-associated crescentic GN. 

PMID- 25762061
TI  - Population movement and sudden cardiac arrest location.
AB  - BACKGROUND: Although the benefits of automatic external defibrillators are
      undeniable, their effectiveness could be dramatically improved. One of the key
      issues is the disparity between the locations of automatic external
      defibrillators and sudden cardiac arrests (SCAs). METHODS AND RESULTS: From
      emergency medical services and other Parisian agencies, data on all SCAs
      occurring in public places in Paris, France, were prospectively collected between
      2000 and 2010 and recorded using 2020 grid areas. For each area, population
      density, population movements, and landmarks were analyzed. Of the 4176 SCAs,
      1255 (30%) occurred in public areas, with a highly clustered distribution of
      SCAs, especially in areas containing major train stations (12% of SCAs in 0.75%
      of the Paris area). The association with population density was poor, with a
      nonsignificant increase in SCAs with population density (P=0.4). Occurrence of
      public SCAs was, in contrast, highly associated with population movements
      (P<0.001). In multivariate analysis including other landmarks in each grid cell
      in the model and demographic characteristics, population movement remained
      significantly associated with the occurrence of SCA (odds ratio, 1.48; 95%
      confidence interval, 1.34-1.63; P<0.0001), as well as grid cells containing train
      stations (odds ratio, 3.80; 95% confidence interval, 2.66-5.36; P<0.0001).
      CONCLUSIONS: Using a systematic analysis of determinants of SCA in public places,
      we demonstrated the extent to which population movements influence SCA
      distribution. Our findings also suggested that beyond this key risk factor, some
      areas are dramatically associated with a higher risk of SCA.

PMID- 25762062
TI  - Reduced fetal cerebral oxygen consumption is associated with smaller brain size
      in fetuses with congenital heart disease.
AB  - BACKGROUND: Fetal hypoxia has been implicated in the abnormal brain development
      seen in newborns with congenital heart disease (CHD). New magnetic resonance
      imaging technology now offers the potential to investigate the relationship
      between fetal hemodynamics and brain dysmaturation. METHODS AND RESULTS: We
      measured fetal brain size, oxygen saturation, and blood flow in the major vessels
      of the fetal circulation in 30 late-gestation fetuses with CHD and 30 normal
      controls using phase-contrast magnetic resonance imaging and T2 mapping. Fetal
      hemodynamic parameters were calculated from a combination of magnetic resonance
      imaging flow and oximetry data and fetal hemoglobin concentrations estimated from
      population averages. In fetuses with CHD, reductions in umbilical vein oxygen
      content (P<0.001) and failure of the normal streaming of oxygenated blood from
      the placenta to the ascending aorta were associated with a mean reduction in
      ascending aortic saturation of 10% (P<0.001), whereas cerebral blood flow and
      cerebral oxygen extraction were no different from those in controls. This
      accounted for the mean 15% reduction in cerebral oxygen delivery (P=0.08) and 32%
      reduction cerebral Vo2 in CHD fetuses (P<0.001), which were associated with a 13%
      reduction in fetal brain volume (P<0.001). Fetal brain size correlated with
      ascending aortic oxygen saturation and cerebral Vo2 (r=0.37, P=0.004).
      CONCLUSIONS: This study supports a direct link between reduced cerebral
      oxygenation and impaired brain growth in fetuses with CHD and raises the
      possibility that in utero brain development could be improved with maternal
      oxygen therapy.

PMID- 25762064
TI  - Targeting the cell wall of Mycobacterium tuberculosis: a molecular modeling
      investigation of the interaction of imipenem and meropenem with L,D
      transpeptidase 2.
AB  - The single crystal X-ray structure of the extracellular portion of the L,D
      transpeptidase (ex-LdtMt2 - residues 120-408) enzyme was recently reported. It
      was observed that imipenem and meropenem inhibit activity of this enzyme,
      responsible for generating L,D-transpeptide linkages in the peptidoglycan layer
      of Mycobacterium tuberculosis. Imipenem is more active and isothermal titration
      calorimetry experiments revealed that meropenem is subjected to an entropy
      penalty upon binding to the enzyme. Herein, we report a molecular modeling
      approach to obtain a molecular view of the inhibitor/enzyme interactions. The
      average binding free energies for nine commercially available inhibitors were
      calculated using MM/GBSA and Solvation Interaction Energy (SIE) approaches and
      the calculated energies corresponded well with the available experimentally
      observed results. The method reproduces the same order of binding energies as
      experimentally observed for imipenem and meropenem. We have also demonstrated
      that SIE is a reasonably accurate and cost-effective free energy method, which
      can be used to predict carbapenem affinities for this enzyme. A theoretical
      explanation was offered for the experimental entropy penalty observed for
      meropenem, creating optimism that this computational model can serve as a
      potential computational model for other researchers in the field. 

PMID- 25762063
TI  - The path forward is to look backward in time: fetal physiology: the new frontier
      in managing infants with congenital heart defects.

PMID- 25762065
TI  - Bayesian modeling of the covariance structure for irregular longitudinal data
      using the partial autocorrelation function.
AB  - In long-term follow-up studies, irregular longitudinal data are observed when
      individuals are assessed repeatedly over time but at uncommon and irregularly
      spaced time points. Modeling the covariance structure for this type of data is
      challenging, as it requires specification of a covariance function that is
      positive definite. Moreover, in certain settings, careful modeling of the
      covariance structure for irregular longitudinal data can be crucial in order to
      ensure no bias arises in the mean structure. Two common settings where this
      occurs are studies with 'outcome-dependent follow-up' and studies with 'ignorable
      missing data'. 'Outcome-dependent follow-up' occurs when individuals with a
      history of poor health outcomes had more follow-up measurements, and the
      intervals between the repeated measurements were shorter. When the follow-up time
      process only depends on previous outcomes, likelihood-based methods can still
      provide consistent estimates of the regression parameters, given that both the
      mean and covariance structures of the irregular longitudinal data are correctly
      specified and no model for the follow-up time process is required. For 'ignorable
      missing data', the missing data mechanism does not need to be specified, but
      valid likelihood-based inference requires correct specification of the covariance
      structure. In both cases, flexible modeling approaches for the covariance
      structure are essential. In this paper, we develop a flexible approach to
      modeling the covariance structure for irregular continuous longitudinal data
      using the partial autocorrelation function and the variance function. In
      particular, we propose semiparametric non-stationary partial autocorrelation
      function models, which do not suffer from complex positive definiteness
      restrictions like the autocorrelation function. We describe a Bayesian approach,
      discuss computational issues, and apply the proposed methods to CD4 count data
      from a pediatric AIDS clinical trial.

PMID- 25762066
TI  - Electromagnetic induction heating for single crystal graphene growth: morphology
      control by rapid heating and quenching.
AB  - The direct observation of single crystal graphene growth and its shape evolution
      is of fundamental importance to the understanding of graphene growth
      physicochemical mechanisms and the achievement of wafer-scale single crystalline
      graphene. Here we demonstrate the controlled formation of single crystal graphene
      with varying shapes, and directly observe the shape evolution of single crystal
      graphene by developing a localized-heating and rapid-quenching chemical vapor
      deposition (CVD) system based on electromagnetic induction heating. Importantly,
      rational control of circular, hexagonal, and dendritic single crystalline
      graphene domains can be readily obtained for the first time by changing the
      growth condition. Systematic studies suggest that the graphene nucleation only
      occurs during the initial stage, while the domain density is independent of the
      growth temperatures due to the surface-limiting effect. In addition, the direct
      observation of graphene domain shape evolution is employed for the identification
      of competing growth mechanisms including diffusion-limited, attachment-limited,
      and detachment-limited processes. Our study not only provides a novel method for
      morphology-controlled graphene synthesis, but also offers fundamental insights
      into the kinetics of single crystal graphene growth. 

PMID- 25762067
TI  - Stable solar-driven oxidation of water by semiconducting photoanodes protected by
      transparent catalytic nickel oxide films.
AB  - Reactively sputtered nickel oxide (NiOx) films provide transparent,
      antireflective, electrically conductive, chemically stable coatings that also are
      highly active electrocatalysts for the oxidation of water to O2(g). These NiOx
      coatings provide protective layers on a variety of technologically important
      semiconducting photoanodes, including textured crystalline Si passivated by
      amorphous silicon, crystalline n-type cadmium telluride, and hydrogenated
      amorphous silicon. Under anodic operation in 1.0 M aqueous potassium hydroxide
      (pH 14) in the presence of simulated sunlight, the NiOx films stabilized all of
      these self-passivating, high-efficiency semiconducting photoelectrodes for >100 h
      of sustained, quantitative solar-driven oxidation of water to O2(g). 

PMID- 25762068
TI  - Correction for Feng et al., Constitutive BDNF/TrkB signaling is required for
      normal cardiac contraction and relaxation.

PMID- 25762069
TI  - Emerging picture of the distinct traits and functions of microvesicles and
      exosomes.

PMID- 25762070
TI  - Selection and identification of ligand peptides targeting a model of castrate
      resistant osteogenic prostate cancer and their receptors.
AB  - We performed combinatorial peptide library screening in vivo on a novel human
      prostate cancer xenograft that is androgen-independent and induces a robust
      osteoblastic reaction in bonelike matrix and soft tissue. We found two peptides,
      PKRGFQD and SNTRVAP, which were enriched in the tumors, targeted the cell surface
      of androgen-independent prostate cancer cells in vitro, and homed to androgen
      receptor-null prostate cancer in vivo. Purification of tumor homogenates by
      affinity chromatography on these peptides and subsequent mass spectrometry
      revealed a receptor for the peptide PKRGFQD, alpha-2-macroglobulin, and for
      SNTRVAP, 78-kDa glucose-regulated protein (GRP78). These results indicate that
      GRP78 and alpha-2-macroglobulin are highly active in osteoblastic, androgen
      independent prostate cancer in vivo. These previously unidentified ligand
      receptor systems should be considered for targeted drug development against human
      metastatic androgen-independent prostate cancer. 

PMID- 25762072
TI  - Correction for Zaslaver et al., Hierarchical sparse coding in the sensory system
      of Caenorhabditis elegans.

PMID- 25762071
TI  - Not-so-early bursts and the dynamic nature of morphological diversification.

PMID- 25762073
TI  - Correction.

PMID- 25762075
TI  - Correction.

PMID- 25762076
TI  - Correction for Hess et al., Glycosylation profiles determine extravasation and
      disease-targeting properties of armed antibodies.

PMID- 25762074
TI  - The Fe-S cluster-containing NEET proteins mitoNEET and NAF-1 as chemotherapeutic
      targets in breast cancer.
AB  - Identification of novel drug targets and chemotherapeutic agents is a high
      priority in the fight against cancer. Here, we report that MAD-28, a designed
      cluvenone (CLV) derivative, binds to and destabilizes two members of a unique
      class of mitochondrial and endoplasmic reticulum (ER) 2Fe-2S proteins, mitoNEET
      (mNT) and nutrient-deprivation autophagy factor-1 (NAF-1), recently implicated in
      cancer cell proliferation. Docking analysis of MAD-28 to mNT/NAF-1 revealed that
      in contrast to CLV, which formed a hydrogen bond network that stabilized the 2Fe
      2S clusters of these proteins, MAD-28 broke the coordinative bond between the His
      ligand and the cluster's Fe of mNT/NAF-1. Analysis of MAD-28 performed with
      control (Michigan Cancer Foundation; MCF-10A) and malignant (M.D. Anderson
      metastatic breast; MDA-MB-231 or MCF-7) human epithelial breast cells revealed
      that MAD-28 had a high specificity in the selective killing of cancer cells,
      without any apparent effects on normal breast cells. MAD-28 was found to target
      the mitochondria of cancer cells and displayed a surprising similarity in its
      effects to the effects of mNT/NAF-1 shRNA suppression in cancer cells, causing a
      decrease in respiration and mitochondrial membrane potential, as well as an
      increase in mitochondrial iron content and glycolysis. As expected, if the NEET
      proteins are targets of MAD-28, cancer cells with suppressed levels of NAF-1 or
      mNT were less susceptible to the drug. Taken together, our results suggest that
      NEET proteins are a novel class of drug targets in the chemotherapeutic treatment
      of breast cancer, and that MAD-28 can now be used as a template for rational drug
      design for NEET Fe-S cluster-destabilizing anticancer drugs. 

PMID- 25762077
TI  - Reply to Zeitzer: Good science, in or out of the laboratory, should prevail.

PMID- 25762078
TI  - Real life trumps laboratory in matters of public health.

PMID- 25762079
TI  - Covert tricuspid valve rupture secondary to blunt chest trauma.

PMID- 25762081
TI  - Corrigendum.
AB  - [This corrects the article DOI: 10.1177/2050640614550672.]. 

PMID- 25762080
TI  - Four-dimensional in vivo X-ray microscopy with projection-guided gating.
AB  - Visualizing fast micrometer scale internal movements of small animals is a key
      challenge for functional anatomy, physiology and biomechanics. We combine phase
      contrast tomographic microscopy (down to 3.3 MUm voxel size) with retrospective,
      projection-based gating (in the order of hundreds of microseconds) to improve the
      spatiotemporal resolution by an order of magnitude over previous studies. We
      demonstrate our method by visualizing 20 three-dimensional snapshots through the
      150 Hz oscillations of the blowfly flight motor. 

PMID- 25762082
TI  - The Fourteenth International Conference on Progress in Vaccination Against Cancer
      (PIVAC-14), September 24-26, 2014, Rome, Italy: rethinking anti-tumor vaccines in
      a new era of cancer immunotherapy.

PMID- 25762084
TI  - Evolution of serum atherogenic risk in liver transplant recipients: Role of
      lipoproteins and metabolic and inflammatory markers.
AB  - Although cardiovascular disease (CVD) is the leading cause of long-term mortality
      in liver transplant recipients (LTRs), the role of recently identified biomarkers
      of CVD risk in liver transplantation is unknown. We aimed to evaluate an
      extensive CVD risk profile in LTRs. Markers of CVD risk in 65 LTRs with no known
      history of diabetes mellitus (DM), dyslipidemia, or ischemic heart disease were
      compared to age-, sex-, and body mass index (BMI)-matched controls with no
      chronic medical disease. LTRs on corticosteroids or those with graft cirrhosis
      (GC) were excluded. The effect of calcineurin inhibitors on the CVD risk profile
      was separately analyzed in LTRs receiving either tacrolimus (Tac) or cyclosporine
      A (CsA). To evaluate the impact of GC, a comparison was made between LTRs with
      and without GC. Non-DM LTRs were matched to controls with respect to age, sex,
      and BMI. LTRs had similar serum high-density lipoprotein-cholesterol (HDL-C), low
      density lipoprotein-cholesterol (LDL-C), and total cholesterol in comparison with
      BMI-matched controls. Proatherogenic small-dense (sd) LDL-C (33.6 +/- 14 versus
      25.9 +/- 9.9 mg/dL; P < 0.001) and %sdLDL-C (30% +/- 10% versus 26.4% +/- 9%; P =
      0.02) were significantly higher in LTRs. In comparison with controls, LTRs had
      higher apolipoprotein B (apoB; 98 +/- 37 versus 88 +/- 24 mg/dL; P < 0.01), very
      low density lipoprotein-particle concentration (VLDL-P; 7.7 +/- 6.7 nmol/L versus
      3.2 +/- 9.1 nmol/L; P < 0.001), and VLDL size (51.1 +/- 6.6 versus 46.5 +/- 6.9
      nm; P < 0.001). In LTRs, VLDL size and VLDL-P were directly related to serum CsA
      levels (r = 0.53, P = 0.09, and r = 0.63, P < 0.01, respectively) but not to Tac
      levels. In comparison with controls, LTRs had significantly lower total serum
      high-density lipoprotein-particle concentration. In comparison with those with
      preserved graft function, LTRs with GC had lower levels of serum atherogenic
      markers characterized by low sdLDL-C, apoB, triglycerides, LDL-C, and total
      cholesterol. In conclusion, LTRs have a proatherogenic lipoprotein profile that
      is not captured with a traditional lipid panel, and this suggests that a detailed
      serum atherogenic profile is needed to truly assess CVD risk in LTRs.

PMID- 25762083
TI  - Quantifying the placebo effect in psychological outcomes of exercise training: a
      meta-analysis of randomized trials.
AB  - BACKGROUND: The placebo effect could account for some or all of the psychological
      benefits attributed to exercise training. The magnitude of the placebo effect in
      psychological outcomes of randomized controlled exercise training trials has not
      been quantified. The aim of this investigation was to estimate the magnitude of
      the population placebo effect in psychological outcomes from placebo conditions
      used in exercise training studies and compare it to the observed effect of
      exercise training. METHODS: Articles published before 1 July 2013 were located
      using Google Scholar, MEDLINE, PsycINFO, and The Cochrane Library. To be included
      in the analysis, studies were required to have (1) a design that randomly
      assigned participants to exercise training, placebo, and control conditions and
      (2) an assessment of a subjective (i.e., anxiety, depression, energy, fatigue) or
      an objective (i.e., cognitive) psychological outcome. Meta-analytic and multi
      level modeling techniques were used to analyze effects from nine studies
      involving 661 participants. Hedges' d effect sizes were calculated, and random
      effects models were used to estimate the overall magnitude of the placebo and
      exercise training effects. RESULTS: After adjusting for nesting effects, the
      placebo mean effect size was 0.20 (95% confidence interval [CI] -0.02, 0.41) and
      the observed effect of exercise training was 0.37 (95% CI 0.11, 0.63).
      CONCLUSION: A small body of research suggests both that (1) the placebo effect is
      approximately half of the observed psychological benefits of exercise training
      and (2) there is an urgent need for creative research specifically aimed at
      better understanding the role of the placebo effect in the mental health
      consequences of exercise training.

PMID- 25762085
TI  - Endograft infection after hybrid surgery for chronic Stanford type B aortic
      dissection: endograft infection and treatment.
AB  - While the incidence of endograft infection is very low, the treatment is
      difficult when it occurs. We herein present the case of a 52-year-old male who
      had undergone a graft replacement in the proximal descending thoracic aorta for
      dissected aortic aneurysm (DA) 6 years previously and hybrid surgery 2 years
      previously, which consisted of an abdominal graft replacement, visceral and renal
      debranching surgery and endovascular surgery for a ruptured abdominal DA and
      residual thoracoabdominal DA. Following collapse from septic shock due to an
      endograft infection, we performed an in situ reconstruction of the entire
      thoracoabdominal aorta following intensive antibiotic therapy and 2 preoperative
      CT-guided percutaneous interventions. He was discharged 4 weeks after the surgery
      without any complications. 

PMID- 25762086
TI  - Zinc-Induced Effects on Osteoclastogenesis Involves Activation of
      Hyperpolarization-Activated Cyclic Nucleotide Modulated Channels via Changes in
      Membrane Potential.
AB  - Zinc is a trace element in the mammalian body, and increasing evidence shows its
      critical role in bone development and osteoclastogenesis. The relationships
      between zinc and voltage-gated ion channels have been reported; however, the
      effects of zinc on membrane potential and the related ion channels remain
      unknown. In this study, we found that zinc-induced hyperpolarization in RAW264.7
      cells (RAW) was promoted by inhibition of hyperpolarization-activated cyclic
      nucleotide modulated channels (HCNs). In electrophysiological experiments with
      RAW-derived osteoclasts, HCNs were functional and generated hyperpolarization
      activated inward currents (Ih) with properties similar to the Ih recorded in
      excitable cells such as neurons and cardiomyocytes. Quantitative PCR of HCN
      subunits HCN1 and HCN4 in RAW cells showed detectable levels of HCN1 mRNA and
      HCN4 expression was the highest of all four subunits. HCN4 knockdown decreased
      osteoclastic Ih and promoted osteoclastogenesis in the presence of zinc, but not
      in the absence of zinc. To determine the effect of membrane hyperpolarization on
      osteoclastogenesis, we developed a light-controllable membrane potential system
      in RAW cells by stably expressing the light-driven outward proton pump,
      Archaerhodopsin3 (Arch). Arch activation by yellow-green light hyperpolarizes the
      cell membrane. Light-induced hyperpolarization accelerated osteoclast
      differentiation in the presence of receptor activator of nuclear factor kappa-B
      ligand (RANKL). Thus, HCN activation reduced the hyperpolarization-related
      promotion of osteoclast differentiation in the presence of zinc. This study
      revealed the novel role of HCN and membrane potential in non-excitable
      osteoclasts.

PMID- 25762087
TI  - Nano-Targeted Delivery of Toremifene, an Estrogen Receptor-alpha Blocker in
      Prostate Cancer.
AB  - PURPOSE: Estrogen Receptor-alpha (ERalpha) expression is increased in prostate
      cancer and acts as an oncogene. We propose that blocking of estrogen hormone
      binding to ERalpha using the ERalpha blocker toremifene will reduce the
      tumorigenicity of prostate cancer, and nano-targeted delivery of toremifene will
      improve anticancer efficacy. We report the synthesis and use in an orthotopic
      mouse model of PLGA-PEG nanoparticles encapsulating toremifene and nanoparticles
      encapsulating toremifene that are also conjugated to anti-PSMA for targeted
      prostate tumor delivery. METHODS: Human prostate cancer cell line PC3M and a nude
      mouse model were used to test efficacy of nano-targeted and nano-encapsulated
      toremifene versus free toremifene on the growth and differentiation of tumor
      cells. RESULTS: Treatment with free toremifene resulted in a significant
      reduction in growth of prostate tumor and proliferation, and its nano-targeting
      resulted in greater reduction of prostate tumor growth, greater toremifene tumor
      uptake, and enhanced tumor necrosis. Tumors from animals treated with nano
      encapsulated toremifene conjugated with anti-PSMA showed about a 15-fold increase
      of toremifene compared to free toremifene. CONCLUSIONS: Our data provide evidence
      that blocking ERalpha by toremifene and targeting prostate cancer tissues with
      anti-PSMA antibody on the nanoparticles' surface repressed the tumorigenicity of
      prostate cancer cells in this mouse model.

PMID- 25762088
TI  - Identification of Nitazoxanide as a Group I Metabotropic Glutamate Receptor
      Negative Modulator for the Treatment of Neuropathic Pain: An In Silico Drug
      Repositioning Study.
AB  - PURPOSE: Drug repositioning strategies were employed to explore new therapeutic
      indications for existing drugs that may exhibit dual negative mGluR1/5 modulating
      activities as potential treatments for neuropathic pain. METHOD: A customized in
      silico-in vitro-in vivo drug repositioning scheme was assembled and implemented
      to search available drug libraries for compounds with dual mGluR1/5 antagonistic
      activities, that were then evaluated using in vitro functional assays and, for
      validated hits, in an established animal model for neuropathic pain. RESULTS:
      Tizoxanide, the primary active metabolite of the FDA approved drug nitazoxanide,
      fit in silico pharmacophore models constructed for both mGluR1 and mGluR5.
      Subsequent calcium (Ca++) mobilization functional assays confirmed that
      tizoxanide exhibited appreciable antagonist activity for both mGluR1 and mGluR5
      (IC50 = 1.8 MUM and 1.2 MUM, respectively). The in vivo efficacy of nitazoxanide
      administered by intraperitoneal injection was demonstrated in a rat model for
      neuropathic pain. CONCLUSION: The major aim of the present study was to
      demonstrate the utility of an in silico-in vitro-in vivo drug repositioning
      protocol to facilitate the repurposing of approved drugs for new therapeutic
      indications. As an example, this particular investigation successfully identified
      nitazoxanide and its metabolite tizoxanide as dual mGluR1/5 negative modulators.
      A key finding is the vital importance for drug screening libraries to include the
      structures of drug active metabolites, such as those emanating from prodrugs
      which are estimated to represent 5-7% of marketed drugs.

PMID- 25762089
TI  - Testing for independence in J*K contingency tables with complex sample survey
      data.
AB  - The test of independence of row and column variables in a (J*K) contingency table
      is a widely used statistical test in many areas of application. For complex
      survey samples, use of the standard Pearson chi-squared test is inappropriate due
      to correlation among units within the same cluster. Rao and Scott (1981, Journal
      of the American Statistical Association 76, 221-230) proposed an approach in
      which the standard Pearson chi-squared statistic is multiplied by a design effect
      to adjust for the complex survey design. Unfortunately, this test fails to exist
      when one of the observed cell counts equals zero. Even with the large samples
      typical of many complex surveys, zero cell counts can occur for rare events,
      small domains, or contingency tables with a large number of cells. Here, we
      propose Wald and score test statistics for independence based on weighted least
      squares estimating equations. In contrast to the Rao-Scott test statistic, the
      proposed Wald and score test statistics always exist. In simulations, the score
      test is found to perform best with respect to type I error. The proposed method
      is motivated by, and applied to, post surgical complications data from the United
      States' Nationwide Inpatient Sample (NIS) complex survey of hospitals in 2008. 

PMID- 25762090
TI  - Salting-in effect in organic dispersions of poly(3-hexyl thiophene)-carbon
      nanotubes.
AB  - Addition of small concentrations of different inorganic salts to THF solutions of
      poly(3-hexyl thiophene), which contain non-dispersed powder of Multi-Walled
      Carbon Nanotubes (MWNTs), was found to "salt-in" the precipitated tubes leading
      to the formation of a stable dispersion of the MWNTs. This effect seems to result
      from a salt-induced conformational change of polymer chains adsorbed onto the
      CNTs, resulting in the onset of (entropic) steric repulsion among polymer
      decorated chains. 

PMID- 25762092
TI  - Uric acid may cause of erectile dysfunction in hypertensive patients?

PMID- 25762091
TI  - p53 target gene Rap2B regulates the cytoskeleton and inhibits cell spreading.
AB  - PURPOSE: Cell migration requires spatiotemporal integration of signals that
      target cytoskeletal. Previous studies have indicated that Rho GTPases are crucial
      regulators of actin dynamics. As homologs of Rho proteins, the role of Rap2B in
      the regulation of cytoskeleton and its cell signaling pathway remains unknown.
      METHODS: The cellular functions of Rap2B were monitored by Western blotting and
      immunofluorescence staining in order to characterize the protein level and the
      cell shape. RESULTS: Here, we show that expression of Rap2B was induced by
      nocodazole in a p53-dependent manner. However, Rap2B itself is not necessary for
      p53-dependent cell cycle arrest. We evidenced that over-expression of Rap2B may
      inhibit cell spreading by disrupting actin dynamics upon nocodazole treatment,
      but Rap2B (C180A) mutant does not. In contrast, knockdown of Rap2B promoted cell
      spreading. CONCLUSIONS: Altogether, these results revealed that Rap2B plays a
      pivotal role in cytoskeleton reorganization and subsequently inhibits cell
      spreading, which could be responsible for cancer metastasis.

PMID- 25762093
TI  - Evaluation and analysis of graft hypertrophy by means of arthroscopy, biochemical
      MRI and osteochondral biopsies in a patient following autologous chondrocyte
      implantation for treatment of a full-thickness-cartilage defect of the knee.
AB  - Graft hypertrophy represents a characteristic complication following autologous
      chondrocyte implantation (ACI) for treatment of cartilage defects. Although some
      epidemiological data suggest that incidence is associated with first-generation
      ACI using autologous chondrocyte implantation, it has also been reported in other
      technical modifications of ACI using different biomaterials. Nevertheless, it has
      not been described in autologous, non-periosteum, implant-free associated ACI. In
      addition, little is known about histological and T2-relaxation appearance of
      graft hypertrophy. The present case report provides a rare case of extensive
      graft hypertrophy following ACI using an autologous spheres technique with
      clinical progression over time. Detailed clinical, MR tomographic and
      histological evaluation has been performed, which demonstrates a high quality of
      repair tissue within the hypertrophic as well as non-hypertrophic transplanted
      areas of the repair tissue. No expression of collagen type X (a sign of
      chondrocyte hypertrophy), only slight changes of the subchondral bone and a
      nearly normal cell-matrix ratio suggest that tissue within the hypertrophic area
      does not significantly differ from intact and high-quality repair tissue and
      therefore seems not to cause graft hypertrophy. This is in contrast to the
      assumption that histological hypertrophy might cause or contribute to an
      overwhelming growth of the repair tissue within the transplantation site. Data
      presented in this manuscript might contribute to further explain the etiology of
      graft hypertrophy following ACI. 

PMID- 25762095
TI  - High porosity supermacroporous polystyrene materials with excellent oil-water
      separation and gas permeability properties.
AB  - Two types of monolith high-porosity supermacroporous polystyrene materials had
      been controlled synthesized from water-in-oil Pickering emulsions. The first
      type, closed-cell high-porosity (up to 91%) supermacroporous (ca. 500 MUm)
      polystyrene materials (CPPs) was prepared by employing amphiphilic carbonaceous
      microspheres (CMs) as high internal phase emulsion stabilizer without any
      inorganic salts or further modifying the wettability of the particles. The second
      type, hierarchical porous polystyrene materials with highly interconnected
      macropores (IPPs), was constructed from emulsions stabilized simultaneously by CM
      particles and a little amount of surfactants. Both types of these monolith porous
      polystyrene materials possessed excellent mechanical strength. The CPPs were used
      as absorbents for oil-water separation and high absorption capacity, and
      absorption rate for oils were realized, which was attributed to their porosity
      structure and the swelling property of the polystyrene, while the IPPs were
      highly permeable for gases due to their interconnected macropores. 

PMID- 25762096
TI  - Characterization of the MCM homohexamer from the thermoacidophilic euryarchaeon
      Picrophilus torridus.
AB  - The typical archaeal MCM exhibits helicase activity independently in vitro. This
      study characterizes MCM from the euryarchaeon Picrophilus torridus. While PtMCM
      hydrolyzes ATP in DNA-independent manner, it displays very poor ability to unwind
      DNA independently, and then too only under acidic conditions. The protein exists
      stably in complex with PtGINS in whole cell lysates, interacting directly with
      PtGINS under neutral and acidic conditions. GINS strongly activates MCM helicase
      activity, but only at low pH. In consonance with this, PtGINS activates PtMCM
      mediated ATP hydrolysis only at low pH, with the amount of ATP hydrolyzed during
      the helicase reaction increasing more than fifty-fold in the presence of GINS.
      While the stimulation of MCM-mediated helicase activity by GINS has been reported
      in MCMs from P.furiosus, T.kodakarensis, and very recently, T.acidophilum, to the
      best of our knowledge, this is the first report of an MCM helicase demonstrating
      DNA unwinding activity only at such acidic pH, across all archaea and eukaryotes.
      PtGINS may induce/stabilize a conducive conformation of PtMCM under acidic
      conditions, favouring PtMCM-mediated DNA unwinding coupled to ATP hydrolysis. Our
      findings underscore the existence of divergent modes of replication regulation
      among archaea and the importance of investigating replication events in more
      archaeal organisms. 

PMID- 25762098
TI  - Dietary Inorganic Chromium in Summer-Exposed Buffalo Calves (Bubalus bubalis):
      Effects on Biomarkers of Heat Stress, Immune Status, and Endocrine Variables.
AB  - The aim of this study was to evaluate the effect of different levels of inorganic
      chromium (Cr) on heat stress, immune response, and hormonal variation in Murrah
      buffalo calves during the summer season. Twenty-four growing Murrah buffalo
      calves were randomly allocated into four treatments for a period of 120 days.
      Feeding regimen was same in all the groups, except the buffalo calves in
      treatment groups were additionally supplemented with 0.5, 1.0, and 1.5 mg of
      inorganic Cr/kg dry matter. Buffalo calves were monitored daily for physiological
      variables and dry matter intake (DMI) and fortnightly for body weight change.
      Blood samples were collected at day 0, 15, 30, 45, 60, 75, 90, 105, and 120 and
      analyzed for heat shock protein 70 (Hsp 70), lymphocyte proliferation, neutrophil
      phagocytic activity, immunoglobulin, ferric reducing antioxidant power (FRAP)
      assay, insulin, cortisol and thyroid hormones, and Cr levels. Dietary Cr
      supplementation did not have any effect on DMI, growth performance, and
      physiological variables. However, lymphocyte proliferation, neutrophil phagocytic
      activity, plasma immunoglobulin, FRAP value, and plasma Cr concentration
      increased significantly (P < 0.05) with increase in levels of Cr. Adding Cr to
      the diet of summer-exposed buffalo calves did not show any effect on plasma
      levels of thyroid hormone, while concentration of insulin, cortisol, and Hsp 70
      decreased (P < 0.05). Supplementation of inorganic Cr to the diet of buffalo
      calves reared under high ambient temperature improved heat tolerance, immune
      status without affecting nutrient intake, and growth performance. 

PMID- 25762099
TI  - Reduction of Oxidative Damage and Inflammatory Response in the Diaphragm Muscle
      of mdx Mice Using Iron Chelator Deferoxamine.
AB  - Oxidative stress and inflammatory processes strongly contribute to pathogenesis
      in Duchenne muscular dystrophy (DMD). Based on evidence that excess iron may
      increase oxidative stress and contribute to the inflammatory response, we
      investigated whether deferoxamine (DFX), a potent iron chelating agent, reduces
      oxidative stress and inflammation in the diaphragm (DIA) muscle of mdx mice (an
      experimental model of DMD). Fourteen-day-old mdx mice received daily
      intraperitoneal injections of DFX at a dose of 150 mg/kg body weight, diluted in
      saline, for 14 days. C57BL/10 and control mdx mice received daily intraperitoneal
      injections of saline only, for 14 days. Grip strength was evaluated as a
      functional measure, and blood samples were collected for biochemical assessment
      of muscle fiber degeneration. In addition, the DIA muscle was removed and
      processed for histopathology and Western blotting analysis. In mdx mice, DFX
      reduced muscle damage and loss of muscle strength. DFX treatment also resulted in
      a significant reduction of dystrophic inflammatory processes, as indicated by
      decreases in the inflammatory area and in NF-kappaB levels. DFX significantly
      decreased oxidative damage, as shown by lower levels of 4-hydroxynonenal and a
      reduction in dihydroethidium staining in the DIA muscle of mdx mice. The results
      of the present study suggest that DFX may be useful in therapeutic strategies to
      ameliorate dystrophic muscle pathology, possibly via mechanisms involving
      oxidative and inflammatory pathways. 

PMID- 25762100
TI  - The Protective Roles of Selenium on Hepatic Tissue Ultrastructure and
      Mitochondrial Antioxidant Capacity in Copper-Overloaded Rats.
AB  - The aim of this study was to explore the effects of selenium addition on hepatic
      tissue ultrastructure and mitochondrial antioxidant capacity in copper-overloaded
      rats. Eighteen adult male Sprague-Dawley (SD) rats were randomly divided into
      three groups (n = 6 per group). Each group received 1 mL (intragastrically) of
      water (control, group I) or water containing copper chloride (CuCl2, 1 mol/L)
      (group II) or a mixture of CuCl2 (1 mol/L) with sodium selenite (Na2SeO3, 0.05
      mol/L) (group III) once daily for 30 days. Histological examination revealed
      normal hepatocyte structure and no ultrastructural changes in mitochondria in
      controls. In contrast, group II exhibited severe ultrastructural alterations,
      fuzzy mitochondrial membranes, irregularly shaped and fragmented rough
      endoplasmic reticulum (RER), and the high melanin content; group III also
      exhibited larger amounts of engulfing vesicles (EV) in the cytoplasm. Compared to
      controls, the CuCl2 treatment lowered (P < 0.05) hepatocyte enzymatic activities
      and increased lipid peroxidation as indicated by an increase in malondialdehyde
      (MDA) levels. The effects of CuCl2 were attenuated by simultaneous administration
      with Na2SeO3. These results indicated that the adverse effects of copper toxicity
      can be partially attenuated by providing a source of selenium. 

PMID- 25762101
TI  - Influence of Ti(4+) on the electrochemical performance of Li-rich layered oxides 
      high power and long cycle life of Li2Ru1-xTixO3 cathodes.
AB  - Li-rich layered oxides are the most attractive cathodes for lithium-ion batteries
      due to their high capacity (>250 mAh g(-1)). However, their application in
      electric vehicles is hampered by low power density and poor cycle life. To
      address these, layered Li2Ru0.75Ti0.25O3 (LRTO) was synthesized and the influence
      of electroinactive Ti(4+) on the electrochemical performance of Li2RuO3 was
      investigated. LRTO exhibited a reversible capacity of 240 mAh g(-1) under 14.3 mA
      g(-1) with 0.11 mol of Li loss after 100 cycles compared to 0.22 mol of Li for
      Li2Ru0.75Sn0.25O3. More Li(+) can be extracted from LRTO (0.96 mol of Li) even
      after 250 cycles at 143 mA g(-1) than Li2RuO3 (0.79 mol of Li). High reversible
      Li extraction and long cycle life were attributed to structural stability of the
      LiM2 layer in the presence of Ti(4+), facilitating the lithium diffusion
      kinetics. The versatility of the Li2MO3 structure may initiate exploration of Ti
      based Li-rich layered oxides for vehicular applications. 

PMID- 25762097
TI  - TOPBP1 recruits TOP2A to ultra-fine anaphase bridges to aid in their resolution.
AB  - During mitosis, sister chromatids must be faithfully segregated to ensure that
      daughter cells receive one copy of each chromosome. However, following
      replication they often remain entangled. Topoisomerase IIalpha (TOP2A) has been
      proposed to resolve such entanglements, but the mechanisms governing TOP2A
      recruitment to these structures remain poorly understood. Here, we identify
      TOPBP1 as a novel interactor of TOP2A, and reveal that it is required for TOP2A
      recruitment to ultra-fine anaphase bridges (UFBs) in mitosis. The C-terminal
      region of TOPBP1 interacts with TOP2A, and TOPBP1 recruitment to UFBs requires
      its BRCT domain 5. Depletion of TOPBP1 leads to accumulation of UFBs, the
      majority of which arise from centromeric loci. Accordingly, expression of a
      TOPBP1 mutant that is defective in TOP2A binding phenocopies TOP2A depletion.
      These findings provide new mechanistic insights into how TOP2A promotes
      resolution of UFBs during mitosis, and highlights a pivotal role for TOPBP1 in
      this process. 

PMID- 25762102
TI  - Multidimensional evaluation of soil pollution from railway tracks.
AB  - Railway transport is a source of pollution to soils and living organisms by e.g.
      PAHs, PCBs, oil-derived products, pesticides and heavy metals. Soil toxicity
      evaluation requires chemical analyses, indicating the type and content of
      particular pollutants, as well as biological analyses, which allow assessing the
      reaction of organisms to these pollutants. This paper is focused on a multi
      aspect evaluation of the degree of toxicity and pollution of soil in selected
      railway areas from north-eastern Poland by application of numerous biotests and
      chemical analyses. The soils were sampled on railway tracks from the following
      railway stations: Bialystok Fabryczny, Siemianowka, Hajnowka, Ilawa Glowna and
      Walily. The most toxic soils occur on the railway tracks at Bialystok Fabryczny
      and Siemianowka. They had a significant toxic effect on test organisms from
      various trophic levels. The contents of PAHs, PCBs, heavy metals, oil-derived
      hydrocarbons and pesticide residues were determined in the examined soils. In all
      cases the detected pollutants did not exceed the admissible levels. The highest
      content of oil-derived substances was noted in soils from Bialystok Fabryczny and
      concentrations were moderate in soils from Siemianowka. Although the pollutants
      determined in soils from railway tracks did not exceed the admissible values,
      they had a toxic effect on numerous test organisms from different trophic levels.
      This suggests a synergistic effect of low concentrations (within the admissible
      levels) of several pollutants together, which resulted in a toxic effect on the
      organisms. Thus, there is a strong need of not only chemical, but also
      ecotoxicological analyses during the evaluation of environmental conditions.
      Based on data obtained from biological and chemical analyses, we concluded that
      railway transport may pose a hazard to the natural environment to a larger extent
      that hitherto expected. 

PMID- 25762103
TI  - Establishment of toxicity thresholds in subpopulations of coelomocytes
      (amoebocytes vs. eleocytes) of Eisenia fetida exposed in vitro to a variety of
      metals: implications for biomarker measurements.
AB  - Coelomocytes comprise the immune system of earthworms and due to their
      sensitivity responding to a wide range of pollutants have been widely used as
      target cells in soil ecotoxicology. Recently, in vitro assays with primary
      cultures of coelomocytes based in the neutral red uptake (NRU) assay have been
      developed as promising tools for toxicity assessment chemical in a reproducible
      and cost-effective manner. However, NRU showed a bimodal dose-response curve
      previously described after in vivo and in vitro exposure of earthworm
      coelomocytes to pollutants. This response could be related with alterations in
      the relative proportion of coelomocyte subpopulations, amoebocytes and eleocytes.
      Thus, the aims of the present work were, first, to establish the toxicity
      thresholds that could be governed by different cell-specific sensitivities of
      coelomocytes subpopulations against a series of metals (Cu, Cd, Pb, Ni), and
      second to understand the implication that coelomocyte population dynamics
      (eleocytes vs. amoebocytes) after exposure to pollutants can have on the
      viability of coelomocytes (measured by NRU assay) as biomarker of general stress
      in soil health assessment. Complementarily flow cytometric analyses were applied
      to obtain correlative information about single cells (amoebocytes and eleocytes)
      in terms of size and complexity, changes in their relative proportion and
      mortality rates. The results indicated a clear difference in sensitivity of
      eleocytes and amoebocytes against metal exposure, being eleocytes more sensitive.
      The bimodal dose-response curve of NRU after in vitro exposure of primary
      cultures of coelomocytes to metals revealed an initial mortality of eleocytes
      (decreased NRU), followed by an increased complexity of amoebocytes (enhanced
      phagocytosis) and massive mortality of eleocytes (increased NRU), to give raise
      to a massive mortality of amoebocytes (decrease NRU). A synergistic effect on NRU
      was exerted by the exposure to high Cu concentrations and acidic pH (elicited by
      the metal itself), whereas the effects on NRU produced after exposure to Cd, Ni
      and Pb were due solely to the presence of metals, being the acidification of
      culture medium meaningless. 

PMID- 25762104
TI  - Trace element analysis of three tissues from Eurasian otters (Lutra lutra) in
      South Korea.
AB  - Eurasian otters (Lutra lutra) are endangered worldwide, but the specific cause of
      their decline has not been determined. This study analyzed the concentrations of
      potentially toxic trace elements, including As, Cd, Pb, Hg, Se, Cu, Mn, and Zn,
      in the liver, kidney, and lung tissues of Eurasian otters in South Korea. There
      were high individual variations in the tissue concentrations of all the elements
      analyzed. The kidneys had the highest concentrations of Cd and Se among the three
      tissue groups, and the livers had the highest concentrations of Cu, Mn, Zn, and
      Hg. The Pb and As concentrations in the livers were not significantly different
      from those in the kidneys, and the lungs had the lowest concentrations of all the
      elements analyzed. The age-related bioaccumulation of Cd and Hg was evident in
      the three tissue groups, and of Se in the kidneys. The Pb concentration was
      higher in the livers of juveniles compared with those of adults and the Zn
      concentration was higher in the lungs of juveniles. There were no apparent gender
      differences in the concentrations of the elements analyzed among the tissue
      groups. The Se concentration correlated with the Hg concentration in the livers
      and kidneys, and with the Cd concentration in the kidneys. The Hg and Cd levels
      correlated in the three tissue groups. The Cu and Zn levels also correlated in
      the livers and kidneys. In general, the element concentrations were within the
      ranges reported by previous studies of this species from European countries,
      except for Cd and Hg, the levels of which were mostly lower than those reported
      previously. These findings may provide baseline information to facilitate the
      conservation of the Eurasian otter. To the best of our knowledge, this is the
      first available study of trace element concentrations in the tissues of Eurasian
      otters from South Korea or Asian countries. 

PMID- 25762105
TI  - Non-tuberculous mycobacterial infection in hospitalized children: a case series.
AB  - Non-tuberculous mycobacteria (NTM) illness is an emerging life-threatening
      infection, and paediatric features have not been well studied. The objective of
      our study was to review the NTM isolates of hospitalized paediatric patients
      identified at our institution and to describe the characteristics of these cases.
      Our retrospective chart review from 2010 to 2013 identified 45 patients with 46
      positive NTM cultures. Fifteen (33%) patients had received haematopoietic cell
      transplant, 13 (29%) had cystic fibrosis, and six (13%) were previously healthy.
      Twenty-seven (59%) NTM isolates were Mycobacterium chelonae/abscessus, 14 (30%)
      were M. avium intracellulare, and four (9%) were M. immunogenum. The majority
      (65%) of cases were community-acquired, and 20 (43%) patients were treated as
      infection. This case series identified a predominance of M. chelonae/abscessus,
      and includes a substantial number of haematopoietic cell transplant patients,
      which reflects the changing spectrum of NTM disease as molecular diagnostics
      improve and quaternary care facilities provide for a larger immunocompromised
      population. 

PMID- 25762106
TI  - Validation of 64Cu-DOTA-rituximab injection preparation under good manufacturing
      practices: a PET tracer for imaging of B-cell non-Hodgkin lymphoma.
AB  - Manufacturing of 64Cu-1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetic
      acid (DOTA)-rituximab injection under good manufacturing practices (GMP) was
      validated for imaging of patients with CD20+ B-cell non-Hodgkin lymphoma.
      Rituximab was purified by size exclusion high performance liquid chromatography
      (HPLC) and conjugated to DOTA-mono-(N-hydroxysuccinimidyl) ester. 64CuCl2,
      buffers, reagents, and other raw materials were obtained as high-grade quality.
      Following a semi-automated synthesis of 64Cu-DOTA-rituximab, a series of quality
      control tests was performed. The product was further tested in vivo using micro
      positron emission tomography/computed tomography (PET/CT) to assess targeting
      ability towards human CD20 in transgenic mice. Three batches of 64Cu-DOTA
      rituximab final product were prepared as per GMP specifications. The
      radiolabeling yield from these batches was 93.1 +/- 5.8%; these provided final
      product with radiopharmaceutical yield, purity, and specific activity of 59.2 +/-
      5.1% (0.9 +/- 0.1 GBq of 64Cu), > 95% (by HPLC and radio-thin layer
      chromatography), and 229.4 +/- 43.3 GBq/umol (or 1.5 +/- 0.3 MBq/ug),
      respectively. The doses passed apyrogenicity and human serum stability
      specifications, were sterile up to 14 days, and retained > 60% immunoreactivity.
      In vivo micro-PET/CT mouse images at 24 hours postinjection showed that the
      tracer targeted the intended sites of human CD20 expression. Thus, we have
      validated the manufacturing of GMP grade 64Cu-DOTA-rituximab for injection in the
      clinical setting.

PMID- 25762107
TI  - Kirenol attenuates experimental autoimmune encephalomyelitis by inhibiting
      differentiation of Th1 and th17 cells and inducing apoptosis of effector T cells.
AB  - Experimental autoimmune encephalomyelitis (EAE), a model of multiple sclerosis
      (MS), is characterized by CNS demyelination mediated by autoreactive T cells.
      Kirenol, a biologically active substance isolated from Herba Siegesbeckiae, has
      potent anti-inflammatory activities. Here we investigated effects of kirenol on
      EAE. Kirenol treatment markedly delayed onset of disease and reduced clinical
      scores in EAE mice. Kirenol treatment reduced expression of IFN-gamma and IL-17A
      in the serum and proportion of Th1 and Th17 cells in draining lymph nodes.
      Priming of lymphocytes was reduced and apoptosis of MOG-activated CD4+ T cells
      was increased in kirenol treated EAE mice. Kirenol treatment of healthy animals
      did not affect the lymphocytes in these non-immunized mice. Further in vitro
      studies showed that kirenol inhibited viability of MOG-specific lymphocytes and
      induced apoptosis of MOG-specific CD4+ T cells in a dose- and time-dependent
      manner. Kirenol treatment upregulated Bax,downregulated Bcl-2,and increased
      activation of caspase-3 and release of cytochrome c, indicating that a
      mitochondrial pathway was involved in kirenol induced apoptosis. Moreover,
      pretreatment with either a pan-caspase inhibitor z-VAD-fmk or a more specific
      caspase 3 inhibitor Ac-DEVD-CHO in lymphocytes reduced kirenol induced apoptosis.
      Our findings implicate kirenol as a useful agent for the treatment of MS. 

PMID- 25762109
TI  - Evaluation of adult attention deficit hyperactivity disorder in smokers and Maras
      powder users.
AB  - BACKGROUND: The aim of this study was to evaluate adult attention deficit and
      hyperactivity disorder (ADHD) in smokers, Maras powder users and non-users of
      tobacco products by using the Adult Attention Deficit and Hyperactivity Disorder
      Self-report Scale (ASRS). METHODS: The study was performed on 446 males
      presenting to family health centers in Kahramanmara, Turkey. Of 446 participants,
      104 were Maras powder users, 133 were smokers and 209 were volunteers not using
      any tobacco products. Data were collected with a questionnaire composed of
      questions about socio-demographic features and features of smoking and Maras
      powder use, and the Fagerstrom Nicotine Dependence Scale and the ASRS. P < 0.05
      was considered significant. RESULTS: The mean age of the participants was 33.94
      +/- 10.68 years (min = 18, max = 64). There was no significant difference in age
      between the study groups (P = 0.089). Thirty-one participants (7.0%) received
      scores higher than the cut-off value (>= 14 points) for the short form of the
      ASRS. Twenty-one participants (4.7%) achieverd scores higher than the cut-off
      value (>= 44 points) for the ASRS. The smokers received the highest scores of
      8.42 +/- 3.79 for all the subscales of the short version of the ASRS, 26.87 +/-
      10.46 for the ASRS, 12.57 +/- 6.47 for the attention deficit subscale and 14.30
      +/- 5.35 for the hyperactivity and impulsivity subscale. CONCLUSION: Higher rates
      of the smokers and the Maras powder users had symptoms of ADHD. Considering
      nicotine may decrease symptoms of ADHD, it can be assumed that the rates of the
      smokers and Maras powder users with ADHD are higher.

PMID- 25762108
TI  - Lamellar keratoplasty treatment of fungal corneal ulcers with acellular porcine
      corneal stroma.
AB  - The fundamental problem of corneal transplantation is a severe shortage of donor
      tissues worldwide, resulting in approximately 1.5 million new cases of blindness
      annually. To explore an alternative to donor corneas, we conducted a clinical
      study in which implanted acellular porcine corneal stromas (APCSs) replaced the
      pathologic anterior corneas in 47 patients who had experienced fungal corneal
      infections. Subsequently, we demonstrated the safety and efficacy of APCSs in
      human keratoplasty for a minimum follow-up period of 6 months, during which time
      no recurrence of infection was observed. All corneal ulcers healed with the
      return of neovascularization. In addition, our results indicated that
      epithelialization occurred in all APCS grafts except four grafts; for these four,
      the grafts dissolved to varying degrees. Furthermore, most porcine grafts (n =
      41) gradually became transparent without rejection, and an improvement of more
      than two lines in best corrected visual acuity (BCVA) was achieved in 34 eyes
      (~72%). Finally, no patients showed any severe adverse reaction or any
      significant change in postoperative systemic safety indicators. Thus, we
      concluded that APCS grafts are safe and efficacious during lamellar keratoplasty
      in treating corneal fungal ulcers and potentially for other clinical diseases. 

PMID- 25762110
TI  - Has the Swap Influenced Aid Flows in the Health Sector?
AB  - The sector wide approach (SWAp) emerged during the 1990s as a mechanism for
      managing aid from the multiplicity of development partners that operate in the
      recipient country's health, education or agricultural sectors. Health SWAps aim
      to give increased control to recipient governments, allowing greater domestic
      influence over how health aid is allocated and facilitating allocative efficiency
      gains. This paper assesses whether health SWAps have increased recipient control
      of health aid via increased general sector-support and have facilitated
      (re)allocations of health aid across disease areas. Using a uniquely compiled
      panel data set of countries receiving development assistance for health over the
      period 1990-2010, we employ fixed effects and dynamic panel models to assess the
      impact of introducing a health SWAp on levels of general sector-support for
      health and allocations of health-sector aid across key funding silos (including
      HIV, 'maternal and child health' and 'sector-support'). Our results suggest that
      health SWAps have influenced health-sector aid flows in a manner consistent with
      increased recipient control and improvements in allocative efficiency.

PMID- 25762111
TI  - Keeping the gate closed: functions of the polycomb repressive complex PRC2 in
      development.
AB  - Plant ontogeny relies on the correct timing and sequence of transitions between
      individual developmental phases. These are specified by gene expression patterns
      that are established by the balanced action of activators and repressors.
      Polycomb repressive complexes (PRCs) represent an evolutionarily conserved system
      of epigenetic gene repression that governs the establishment and maintenance of
      cell, tissue and organ identity, contributing to the correct execution of the
      developmental programs. PRC2 is a four-subunit histone methyltransferase complex
      that catalyzes trimethylation of lysine 27 on histone H3 (H3K27me3), which
      contributes to the change of chromatin structure and long-lasting gene
      repression. Here, we review the composition and molecular function of the
      different known PRC2 complexes in plants, and focus on the role of PRC2 in
      mediating the establishment of different developmental phases and transitions
      between them.

PMID- 25762112
TI  - Testing ecological theories with sequence similarity networks: marine ciliates
      exhibit similar geographic dispersal patterns as multicellular organisms.
AB  - BACKGROUND: High-throughput sequencing technologies are lifting major limitations
      to molecular-based ecological studies of eukaryotic microbial diversity, but
      analyses of the resulting millions of short sequences remain a major bottleneck
      for these approaches. Here, we introduce the analytical and statistical framework
      of sequence similarity networks, increasingly used in evolutionary studies and
      graph theory, into the field of ecology to analyze novel pyrosequenced V4 small
      subunit rDNA (SSU-rDNA) sequence data sets in the context of previous studies,
      including SSU-rDNA Sanger sequence data from cultured ciliates and from previous
      environmental diversity inventories. RESULTS: Our broadly applicable protocol
      quantified the progress in the description of genetic diversity of ciliates by
      environmental SSU-rDNA surveys, detected a fundamental historical bias in the
      tendency to recover already known groups in these surveys, and revealed
      substantial amounts of hidden microbial diversity. Moreover, network measures
      demonstrated that ciliates are not globally dispersed, but are structured by
      habitat and geographical location at intermediate geographical scale, as observed
      for bacteria, plants, and animals. CONCLUSIONS: Currently available 'universal'
      primers used for local in-depth sequencing surveys provide little hope to exhaust
      the significantly higher ciliate (and most likely microbial) diversity than
      previously thought. Network analyses such as presented in this study offer a
      promising way to guide the design of novel primers and to further explore this
      vast and structured microbial diversity.

PMID- 25762113
TI  - Paediatric ventilation treatment of acute lung injury in Nordic intensive care
      units.
AB  - BACKGROUND: Treatment of acute respiratory distress syndrome (ARDS) in children
      is largely based on extrapolated knowledge obtained from adults and which varies
      between different hospitals. This study explores ventilation treatment strategies
      for children with ARDS in the Nordic countries, and compares these with
      international practice. METHODS: In October 2012, a questionnaire covering
      ventilation treatment strategies for children aged 1 month to 6 years of age with
      ARDS was sent to 21 large Nordic intensive care units that treat children with
      ARDS. Pre-terms and children with congenital conditions were excluded. RESULTS:
      Eighteen of the 21 (86%) targeted intensive care units responded to the
      questionnaire. Fifty per cent of these facilities were paediatric intensive care
      units. Written guidelines existed in 44% of the units. Fifty per cent of the
      units frequently used cuffed endotracheal tubes. Ventilation was achieved by
      pressure control for 89% vs. volume control for 11% of units. Bronchodilators
      were used by all units, whereas steroids usage was 83% and surfactant 39%.
      Inhaled nitric oxide and high frequency oscillation were available in 94% of the
      units. Neurally adjusted ventilator assist was used by 44% of the units.
      Extracorporeal membrane oxygenation could be started in 44% of the units.
      CONCLUSION: Ventilation treatment strategies for paediatric ARDS in the Nordic
      countries are relatively uniform and largely in accordance with international
      practice. The use of steroids and surfactant is more frequent than shown in other
      studies.

PMID- 25762114
TI  - Revealing the cellular localization of STAT1 during the cell cycle by super
      resolution imaging.
AB  - Signal transducers and activators of transcription (STATs) can transduce cytokine
      signals and regulate gene expression. The cellular localization and nuclear
      trafficking of STAT1, a representative of the STAT family with multiple
      transcriptional functions, is tightly related with transcription process, which
      usually happens in the interphase of the cell cycle. However, these priority
      questions regarding STAT1 distribution and localization at the different cell
      cycle stages remain unclear. By using direct stochastic optical reconstruction
      microscopy (dSTORM), we found that the nuclear expression level of STAT1
      increased gradually as the cell cycle carried out, especially after EGF
      stimulation. Furthermore, STAT1 formed clusters in the whole cell during the cell
      cycle, with the size and the number of clusters also increasing significantly
      from G1 to G2 phase, suggesting that transcription and other cell-cycle related
      activities can promote STAT1 to form more and larger clusters for fast response
      to signals. Our work reveals that the cellular localization and clustering
      distribution of STAT1 are associated with the cell cycle, and further provides an
      insight into the mechanism of cell-cycle regulated STAT1 signal transduction. 

PMID- 25762115
TI  - HIV-Risk Related Attitudes and Behaviors Among Older Impoverished Women Living in
      Puerto Rico.
AB  - HIV has increasingly impacted older adults regarding sero-prevalence and sero
      incidence as long-term survivors of HIV/AIDS are living longer. This study
      examines the relationship between age and HIV-related attitudes and risk
      behaviors among female public housing residents in Puerto Rico. Using a self
      administered survey instrument, 1,138 female public housing residents were
      surveyed between April and August 2006. Bivariate results showed that older women
      (aged 50+ years) were significantly less likely to report HIV testing and to
      discuss safer sex with their most recent "steady" sex partner than women under
      the age of 50 years. Older women were also more likely to express anxiety
      associated with condoms and more barriers to using condoms. The older versus
      younger groups did not significantly differ regarding condom use, which was
      extremely low across the groups. In the past three and 12 months, older women
      were less likely than younger women to report having (a) multiple sex partners
      and; (b) oral and anal sex with their most recent steady sex partner; (c) oral
      sex with their most recent non-steady sex partner and, (d) engaging in sexual
      activity in the previous three and 12 months. Age-specific messages concerning
      their increased risk of HIV among other interventions would likely curtail the
      increase in the number of new HIV cases being reported among members of this sub
      population. 

PMID- 25762116
TI  - Erratum to: Korean American Women and Mammogram Uptake.
AB  - Erratum to: J Immigrant Minority Health, DOI 10.1007/s10903-015-0164-6. The names
      of two of the authors (Eunice E. Lee and Kyeung Mi Oh) were incorrect in the
      original publication. The correct names are shown here.

PMID- 25762117
TI  - Novel therapeutic targets of metformin: metabolic syndrome and cardiovascular
      disease.
AB  - INTRODUCTION: Metformin is a widely used drug in the treatment of type 2 diabetes
      mellitus (T2DM). However, it is becoming an attractive drug to manage patients
      with pre-diabetes and to possibly prevent cardiac remodeling and fibrosis and
      heart failure. AREAS COVERED: In this review, we highlight the novel therapeutic
      targets of metformin with a special emphasis on cardiovascular disease. We
      discuss its key mechanisms of action and new signaling pathways that could
      partially account for its effect. Furthermore, metformin's role in the management
      of patients with metabolic syndrome is debated, emphasizing its potential to
      prevent diabetic heart disease. On the other hand, intense research is ongoing to
      clarify if metformin will be a future drug to target ischemia-reperfusion injury
      in the setting of myocardial ischemia. EXPERT OPINION: In the following years,
      one should look carefully at basic science results to successfully design and
      conduct clinical trials, emphasizing patients without full-blown T2DM, but who
      otherwise might have increased insulin resistance. Topics such as the prevention
      of cardiac fibrosis and heart failure with preserved ejection fraction, the
      attenuation of ischemia-reperfusion injury on an acute coronary syndrome and the
      post-myocardial infarction left ventricle remodeling surely deserve a special
      interest and should be faced as potential therapeutic targets for metformin.

PMID- 25762118
TI  - Analytical three-point Dixon method: With applications for spiral water-fat
      imaging.
AB  - PURPOSE: The goal of this work is to present a new three-point analytical
      approach with flexible even or uneven echo increments for water-fat separation
      and to evaluate its feasibility with spiral imaging. THEORY AND METHODS: Two sets
      of possible solutions of water and fat are first found analytically. Then, two
      field maps of the B0 inhomogeneity are obtained by linear regression. The initial
      identification of the true solution is facilitated by the root-mean-square error
      of the linear regression and the incorporation of a fat spectrum model. The
      resolved field map after a region-growing algorithm is refined iteratively for
      spiral imaging. The final water and fat images are recalculated using a joint
      water-fat separation and deblurring algorithm. RESULTS: Successful
      implementations were demonstrated with three-dimensional gradient-echo head
      imaging and single breathhold abdominal imaging. Spiral, high-resolution T1 
      weighted brain images were shown with comparable sharpness to the reference
      Cartesian images. CONCLUSION: With appropriate choices of uneven echo increments,
      it is feasible to resolve the aliasing of the field map voxel-wise. High-quality
      water-fat spiral imaging can be achieved with the proposed approach.

PMID- 25762119
TI  - Pharyngocutaneous fistula after salvage laryngectomy.
AB  - CONCLUSION: Preoperative chemoradiotherapy (CRT) was associated with a
      significantly higher rate of pharyngocutaneous fistula (PCF). OBJECTIVE: PCF is
      the most frequent complication following total laryngectomy. Although organ
      preserving radiotherapy (RT) or CRT offer good locoregional control, many
      patients still require salvage laryngectomy. The aim of this study was to
      evaluate the factors that predispose patients to PCF, with a focus on
      preoperative RT, induction chemotherapy (ICT), and CRT. METHODS: This was a
      retrospective case series; 151 patients who underwent TL were reviewed.
      Preoperative RT, ICT, CRT, and some surgical parameters were analyzed as
      potential risk factors. RESULTS: The overall PCF rate was 13%. CRT was the only
      preoperative treatment that had a significant effect on PCF (35.3%, p = 0.004,
      odds ratio (OR) = 10.75). Surgery extended to the pharynx (p = 0.005, OR = 8.34)
      and vacuum drain duration (p = 0.012, OR = 5.16) were observed to be associated
      with PCF.

PMID- 25762120
TI  - Laughter's influence on the intimacy of self-disclosure.
AB  - If laughter functions to build relationships between individuals, as current
      theory suggests, laughter should be linked to interpersonal behaviors that have
      been shown to be critical to relationship development. Given the importance of
      disclosing behaviors in facilitating the development of intense social bonds, it
      is possible that the act of laughing may temporarily influence the laugher's
      willingness to disclose personal information. We tested this hypothesis
      experimentally by comparing the characteristics of self-disclosing statements
      produced by those who had previously watched one of three video clips that
      differed in the extent to which they elicited laughter and positive affect. The
      results show that disclosure intimacy is significantly higher after laughter than
      in the control condition, suggesting that this effect may be due, at least in
      part, to laughter itself and not simply to a change in positive affect. However,
      the disclosure intimacy effect was only found for observers' ratings of
      participants' disclosures and was absent in the participants' own ratings. We
      suggest that laughter increases people's willingness to disclose, but that they
      may not necessarily be aware that it is doing so. 

PMID- 25762121
TI  - Corticosteroids in the management of prostate cancer: a critical review.
AB  - Corticosteroids have been used in the management of prostate cancer for over 30
      years. Although daily oral corticosteroids have frequently used in conjunction
      with chemotherapy for metastatic castration-resistant prostate cancer, their
      independent impact on survival is unclear. However, corticosteroids confer
      palliative benefits and are associated with objective responses and circulating
      tumor cell (CTC) and PSA declines in a small minority of patients, although
      toxicities such as osteoporosis and immunosuppression complicate long-term use.
      Following the demonstration of a palliative benefit for mitoxantrone combined
      with corticosteroids compared with corticosteroids alone, subsequent trials that
      demonstrated a benefit for first-line docetaxel over mitoxantrone, and second
      line cabazitaxel over mitoxantrone, administered concurrent daily oral
      corticosteroids with all of these agents to maintain uniformity. Conversely,
      improved outcomes were demonstrated with docetaxel without corticosteroids for
      metastatic castration-sensitive prostate cancer. Daily oral corticosteroids are
      routinely combined with abiraterone to mitigate symptoms of mineralocorticoid
      excess. In contrast daily corticosteroids are not essential when administering
      enzalutamide or radium-223, and there is a concern of deleterious immune effects
      concurrently with sipuleucel-T. Given emerging evidence for promotion of
      resistance mechanisms, routine administration of daily oral corticosteroids in
      settings other than abiraterone administration and palliation of symptoms is
      probably not required.

PMID- 25762122
TI  - Incidence of adult T-cell leukemia/lymphoma in nonendemic areas.
AB  - Adult T-cell leukemia/lymphoma (ATLL) is a mature T-cell neoplasm with extremely
      poor prognosis caused by human T-cell leukemia virus type 1 (HTLV-1). The
      distribution of HTLV-1 and the incidence of ATLL in endemic areas have been well
      described, however, little is known about the incidences and the trends of the
      disease in nonendemic areas. Recently, studies have shown that the HTLV-1
      carriers are increasing in nonendemic areas. Also, the incidence of ATLL seems to
      be significantly increasing in nonendemic areas suggesting that HTLV-1 carriers
      have emigrated from endemic areas. These epidemiologic studies indicate the
      necessity of edification of the disease caused by HTLV-1 and establishing
      appropriate preventive methods against infection in nonendemic areas. 

PMID- 25762123
TI  - Familial leukemias.
AB  - Familial leukemia has been described for more than 50 years but only recently
      have modern genetic techniques allowed for the investigation of the genome.
      Genome-wide association studies have identified a number of genetic sites that
      appear to relate to susceptibility to leukemia in certain families and
      occasionally to susceptibility to a specific leukemia in general. Many questions
      remain, including susceptibility to what? An oncogenic virus? An environmental
      chemical? Mutation of another gene induced by a heritable mutation-promoting
      gene?.Clinically important facts have been learned. Chronic lymphocytic leukemia
      (CLL) is by far the most common familial leukemia. Patients with CLL have
      approximately a 10% chance of a first-degree relative developing CLL, and even a
      greater chance of one developing monoclonal B-cell lymphocytosis which may be an
      asymptomatic forme fruste of the neoplasm. Furthermore, there may be an increased
      incidence of breast cancer in familial CLL pedigrees which raises the question of
      a common etiology for neoplasms in general, or at least a previously unrecognized
      relationship among them.

PMID- 25762124
TI  - The evolving role of cytotoxic chemotherapy in the management of patients with
      metastatic prostate cancer.
AB  - Prostate cancer (PC) is the most common cancer in men in the United States.
      Although outcomes are excellent for early-stage disease, survival for men with
      metastatic PC is limited. While older studies did not supported the use of
      chemotherapy in PC, the efficacy of taxane chemotherapy plus prednisone is now
      well established in men with metastatic castration resistant PC (CRPC). The
      results of CHAARTED trial have further expanded the use of chemotherapy to
      patients with metastatic hormone-sensitive disease. The clinical efficacy of
      taxanes over other chemotherapeutics may be a result of its ability to inhibit
      microtubule-dependent trafficking of proteins such as the androgen-receptor (AR).
      Ongoing research uses chemotherapy earlier in the disease course as well as
      explores the utility of combining cytotoxic chemotherapy with biologic agents.

PMID- 25762125
TI  - Improvements and innovations in endoscopic ultrasound guided fine needle
      aspiration.

PMID- 25762126
TI  - Association between individual response to food taste and gastroesophageal
      symptoms.
AB  - OBJECTIVE: Taste is an important element in food preferences. Gastroesophageal
      reflux disease (GERD) is related to lifestyles including eating habits. We aimed
      to investigate the relationship between responses to specific tastes and GERD.
      METHODS: Altogether 280 patients including 170 men with a mean age of 58.6 years
      were included in the study to determine the relationship between their liking for
      specific tastes and GERD using a new self-administered questionnaire (responses
      to various tastes and participants' sensitivity to taste and hot food and on the
      frequency of stomatitis). Another self-administrated questionnaire was
      administrated for a diagnosis of GERD (the frequency scale for the symptoms of
      GERD cut-off score of 10). Furthermore, 142 of 280 patients who had received
      esophagogastroduodenoscopy (EGD) were investigated on the association between
      endoscopic esophagitis and their favorite tastes. RESULTS: In the association
      analyses between responses to specific tastes and GERD, the group liking salty
      food and the group with a high frequency of stomatitis had a significantly higher
      incidence of GERD (salty food: odds ratio [OR] 2.059, 95% confidence interval
      [CI] 1.215-3.488, P = 0.0073; stomatitis: OR 2.861, 95% CI 1.558-5.253, P =
      0.0007, respectively). In association analyses with endoscopic esophagitis, the
      groups liking salty and sour food had a significantly higher incidence rate of
      endoscopic esophagitis (salty: OR 2.718, 95% CI 1.330-5.555, P = 0.0061; sour: OR
      3.267, 95% CI 1.491-7.160, P = 0.0031, respectively). CONCLUSIONS: Sensitivity
      and response to specific food taste were associated with GERD. The results of a
      preference to hot or salty food and endoscopic esophagitis suggest that physical
      stimuli are important for esophageal injuries.

PMID- 25762127
TI  - Anti-inflammatory components of the Vietnamese starfish Protoreaster nodosus.
AB  - BACKGROUND: In the present study, we examined the inhibitory effects of a
      methanolic extract, dichloromethane fraction, water layer, and polyhydroxylated
      sterols (1-4) isolated from the Vietnamese starfish Protoreaster nodosus on pro
      inflammatory cytokine (IL-12 p40, IL-6, and TNF-alpha) production in LPS
      stimulated bone marrow-derived dendritic cells (BMDCs) using enzyme-linked
      immunosorbent assays (ELISA). RESULTS: The methanolic extract and dichloromethane
      fraction exerted potent inhibitory effects on the production of all three pro
      inflammatory cytokines, with IC50 values ranging from 0.60 +/- 0.01 to 26.19 +/-
      0.64 MUg/mL. Four highly pure steroid derivatives (1-4) were isolated from the
      dichloromethane fraction and water layer of P. nodosus. Potent inhibitory
      activities were also observed for (25S) 5alpha-cholestane
      3beta,4beta,6alpha,7alpha,8beta,15alpha,16beta,26-octol (3) on the production of
      IL-12 p40 and IL-6 (IC50s = 3.11 +/- 0.08 and 1.35 +/- 0.03 MUM), and for (25S)
      5alpha-cholestane-3beta,6alpha,8beta,15alpha,16beta,26-hexol (1) and (25S) 5alpha
      cholestane-3beta,6alpha,7alpha,8beta,15alpha,16beta,26-heptol (2) on the
      production of IL-12 p40 (IC50s = 0.01 +/- 0.00 and 1.02 +/- 0.01 MUM). Moreover,
      nodososide (4) exhibited moderate inhibitory effects on IL-12 p40 and IL-6
      production. CONCLUSION: This is the first report of the anti-inflammatory
      activity from the starfish P. nodosus. The main finding of this study is the
      identification oxygenated steroid derivatives from P. nodosus with potent anti
      inflammatory activities that may be developed as therapeutic agents for
      inflammatory diseases.

PMID- 25762129
TI  - Two-year outcome of an observe-and-plan regimen for neovascular age-related
      macular degeneration: how to alleviate the clinical burden with maintained
      functional results.

PMID- 25762130
TI  - Choroid thickness and ocular pulse amplitude in migraine during attack.

PMID- 25762128
TI  - Regulatory-auxiliary subunits of CLC chloride channel-transport proteins.
AB  - The CLC family of chloride channels and transporters is composed by nine members,
      but only three of them, ClC-Ka/b, ClC-7 and ClC-2, have been found so far
      associated with auxiliary subunits. These CLC regulatory subunits are small
      proteins that present few common characteristics among them, both structurally
      and functionally, and their effects on the corresponding CLC protein are
      different. Barttin, a protein with two transmembrane domains, is essential for
      the membrane localization of ClC-K proteins and their activity in the kidney and
      inner ear. Ostm1 is a protein with a single transmembrane domain and a highly
      glycosylated N-terminus. Unlike the other two CLC auxiliary subunits, Ostm1 shows
      a reciprocal relationship with ClC-7 for their stability. The subcellular
      localization of Ostm1 depends on ClC-7 and not the other way around. ClC-2 is
      active on its own, but GlialCAM, a transmembrane cell adhesion molecule with two
      extracellular immunoglobulin (Ig)-like domains, regulates its subcellular
      localization and activity in glial cells. The common theme for these three
      proteins is their requirement for a proper homeostasis, since their malfunction
      leads to distinct diseases. We will review here their properties and their role
      in normal chloride physiology and the pathological consequences of their improper
      function. 

PMID- 25762131
TI  - qAC2, a novel QTL that interacts with Wx and controls the low amylose content in
      rice (Oryza sativa L.).
AB  - KEY MESSAGE: This manuscript reports the fine mapping of a novel QTL, qAC2
      controlling the low amylose in rice. The action mechanism of the qAC2 is also
      investigated by the analysis of genetic interactions to Wx (a), Wx (b), du1, du2
      and du3. Amylose content of the rice (Oryza sativa L.) endosperm greatly affects
      starch properties and eating quality of cooked rice. Seeds of japonica rice
      cultivar Kuiku162 have low amylose content (AC) and good eating quality. Our
      analysis revealed a novel QTL, designated as qAC2 that contributed to the low AC
      of Kuiku162. qAC2 was fine mapped within a 74.9-kb region between two insertion
      and deletion markers, KID3001 and KID5101, on the long arm of chromosome 2. Seven
      genes are predicted in this region, but none of them is known to be related to
      the regulation of AC. The AC of a near-isogenic line (NIL110) carrying qAC2
      (Kuiku), the Kuiku162 allele of qAC2, in the genetic background of japonica
      cultivar Itadaki was lower by 1.1% points than that of Itadaki. The chain length
      distributions of amylopectin were similar in NIL110 and Itadaki; therefore, the
      low AC of NIL110 was caused by a decrease in the actual AC, but not by a
      difference in the amylopectin structure. The interaction analyses revealed that
      qAC2 (Kuiku) has epistatic interaction with Wx (a). The qAC2 (Kuiku) has
      epistatic interactions with two loci, du1 and du2, on Wx (b), whereas the genetic
      effect of qAC2 (Kuiku) has additive to that of du3 on Wx (b). Thus, similar to
      du1 and du2, qAC2 may have a function related to Wx (b) mRNA splicing.

PMID- 25762132
TI  - Genetic and agronomic assessment of cob traits in corn under low and normal
      nitrogen management conditions.
AB  - KEY MESSAGE: Exploring and understanding the genetic basis of cob biomass in
      relation to grain yield under varying nitrogen management regimes will help
      breeders to develop dual-purpose maize. With rising energy demands and costs for
      fossil fuels, alternative energy from renewable sources such as maize cobs will
      become competitive. Maize cobs have beneficial characteristics for utilization as
      feedstock including compact tissue, high cellulose content, and low ash and
      nitrogen content. Nitrogen is quantitatively the most important nutrient for
      plant growth. However, the influence of nitrogen fertilization on maize cob
      production is unclear. In this study, quantitative trait loci (QTL) have been
      analyzed for cob morphological traits such as cob weight, volume, length,
      diameter and cob tissue density, and grain yield under normal and low nitrogen
      regimes. 213 doubled-haploid lines of the intermated B73 * Mo17 (IBM) Syn10
      population have been resequenced for 8575 bins, based on SNP markers. A total of
      138 QTL were found for six traits across six trials using composite interval
      mapping with ten cofactors and empirical comparison-wise thresholds (P = 0.001).
      Despite moderate to high repeatabilities across trials, few QTL were consistent
      across trials and overall levels of explained phenotypic variance were lower than
      expected some of the cob trait * trial combinations (R (2) = 7.3-43.1 %).
      Variation for cob traits was less affected by nitrogen conditions than by grain
      yield. Thus, the economics of cob usage under low nitrogen regimes is promising.

PMID- 25762134
TI  - Coronary spasm secondary to hypocalcaemia and hypomagnesaemia.

PMID- 25762133
TI  - Issues encountered in recent attempts to develop novel antidepressant agents.
AB  - The development of new antidepressants has had mixed results over the past
      decade, with several notable failures. This paper reviews a number of major
      initiatives in the development of new antidepressant agents. Traditional
      strategies to build on agents that have monoaminergic effects at the synapse
      (e.g., vilazodone and ketamine) have been complemented with efforts that have
      emphasized devices and brain circuits (e.g., deep brain stimulation and
      transcranial magnetic stimulation) or chemical agents that modulate
      neuroendocrine systems (e.g., glucocorticoid antagonists, mixed melatonin
      agonists/serotonin type-2 receptor antagonists). Interestingly, chemical agents,
      such as onabotulinumtoxin A, may affect brain circuits as well. We present data
      from recent studies in drug and device development--reviewing progress made,
      stumbling blocks encountered, and issues that need to be addressed in future
      studies.

PMID- 25762135
TI  - [Syncope in the course of paroxysmal atrioventricular block third degree detected
      by implantable ECG recorder].

PMID- 25762136
TI  - Disruption of DNA-methylation-dependent long gene repression in Rett syndrome.
AB  - Disruption of the MECP2 gene leads to Rett syndrome (RTT), a severe neurological
      disorder with features of autism. MECP2 encodes a methyl-DNA-binding protein that
      has been proposed to function as a transcriptional repressor, but despite
      numerous mouse studies examining neuronal gene expression in Mecp2 mutants, no
      clear model has emerged for how MeCP2 protein regulates transcription. Here we
      identify a genome-wide length-dependent increase in gene expression in MeCP2
      mutant mouse models and human RTT brains. We present evidence that MeCP2
      represses gene expression by binding to methylated CA sites within long genes,
      and that in neurons lacking MeCP2, decreasing the expression of long genes
      attenuates RTT-associated cellular deficits. In addition, we find that long genes
      as a population are enriched for neuronal functions and selectively expressed in
      the brain. These findings suggest that mutations in MeCP2 may cause neurological
      dysfunction by specifically disrupting long gene expression in the brain. 

PMID- 25762137
TI  - Visualizing transient Watson-Crick-like mispairs in DNA and RNA duplexes.
AB  - Rare tautomeric and anionic nucleobases are believed to have fundamental
      biological roles, but their prevalence and functional importance has remained
      elusive because they exist transiently, in low abundance, and involve subtle
      movements of protons that are difficult to visualize. Using NMR relaxation
      dispersion, we show here that wobble dG*dT and rG*rU mispairs in DNA and RNA
      duplexes exist in dynamic equilibrium with short-lived, low-populated Watson
      Crick-like mispairs that are stabilized by rare enolic or anionic bases. These
      mispairs can evade Watson-Crick fidelity checkpoints and form with probabilities
      (10(-3) to 10(-5)) that strongly imply a universal role in replication and
      translation errors. Our results indicate that rare tautomeric and anionic bases
      are widespread in nucleic acids, expanding their structural and functional
      complexity beyond that attainable with canonical bases. 

PMID- 25762138
TI  - Crystal structure of the eukaryotic origin recognition complex.
AB  - Initiation of cellular DNA replication is tightly controlled to sustain genomic
      integrity. In eukaryotes, the heterohexameric origin recognition complex (ORC) is
      essential for coordinating replication onset. Here we describe the crystal
      structure of Drosophila ORC at 3.5 A resolution, showing that the 270 kilodalton
      initiator core complex comprises a two-layered notched ring in which a collar of
      winged-helix domains from the Orc1-5 subunits sits atop a layer of AAA+ (ATPases
      associated with a variety of cellular activities) folds. Although canonical inter
      AAA+ domain interactions exist between four of the six ORC subunits,
      unanticipated features are also evident. These include highly interdigitated
      domain-swapping interactions between the winged-helix folds and AAA+ modules of
      neighbouring protomers, and a quasi-spiral arrangement of DNA binding elements
      that circumnavigate an approximately 20 A wide channel in the centre of the
      complex. Comparative analyses indicate that ORC encircles DNA, using its winged
      helix domain face to engage the mini-chromosome maintenance 2-7 (MCM2-7) complex
      during replicative helicase loading; however, an observed out-of-plane rotation
      of more than 90 degrees  for the Orc1 AAA+ domain disrupts interactions with
      catalytic amino acids in Orc4, narrowing and sealing off entry into the central
      channel. Prima facie, our data indicate that Drosophila ORC can switch between
      active and autoinhibited conformations, suggesting a novel means for cell cycle
      and/or developmental control of ORC functions. 

PMID- 25762139
TI  - Cancer immunotherapy: dendritic-cell vaccines on the move.

PMID- 25762142
TI  - Systems biology: Defiant daughters and coordinated cousins.

PMID- 25762143
TI  - Lineage correlations of single cell division time as a probe of cell-cycle
      dynamics.
AB  - Stochastic processes in cells are associated with fluctuations in mRNA, protein
      production and degradation, noisy partition of cellular components at division,
      and other cell processes. Variability within a clonal population of cells
      originates from such stochastic processes, which may be amplified or reduced by
      deterministic factors. Cell-to-cell variability, such as that seen in the
      heterogeneous response of bacteria to antibiotics, or of cancer cells to
      treatment, is understood as the inevitable consequence of stochasticity.
      Variability in cell-cycle duration was observed long ago; however, its sources
      are still unknown. A central question is whether the variance of the observed
      distribution originates from stochastic processes, or whether it arises mostly
      from a deterministic process that only appears to be random. A surprising feature
      of cell-cycle-duration inheritance is that it seems to be lost within one
      generation but to be still present in the next generation, generating poor
      correlation between mother and daughter cells but high correlation between cousin
      cells. This observation suggests the existence of underlying deterministic
      factors that determine the main part of cell-to-cell variability. We developed an
      experimental system that precisely measures the cell-cycle duration of thousands
      of mammalian cells along several generations and a mathematical framework that
      allows discrimination between stochastic and deterministic processes in lineages
      of cells. We show that the inter- and intra-generation correlations reveal
      complex inheritance of the cell-cycle duration. Finally, we build a deterministic
      nonlinear toy model for cell-cycle inheritance that reproduces the main features
      of our data. Our approach constitutes a general method to identify deterministic
      variability in lineages of cells or organisms, which may help to predict and,
      eventually, reduce cell-to-cell heterogeneity in various systems, such as cancer
      cells under treatment. 

PMID- 25762141
TI  - Tetanus toxoid and CCL3 improve dendritic cell vaccines in mice and glioblastoma
      patients.
AB  - After stimulation, dendritic cells (DCs) mature and migrate to draining lymph
      nodes to induce immune responses. As such, autologous DCs generated ex vivo have
      been pulsed with tumour antigens and injected back into patients as
      immunotherapy. While DC vaccines have shown limited promise in the treatment of
      patients with advanced cancers including glioblastoma, the factors dictating DC
      vaccine efficacy remain poorly understood. Here we show that pre-conditioning the
      vaccine site with a potent recall antigen such as tetanus/diphtheria (Td) toxoid
      can significantly improve the lymph node homing and efficacy of tumour-antigen
      specific DCs. To assess the effect of vaccine site pre-conditioning in humans, we
      randomized patients with glioblastoma to pre-conditioning with either mature DCs
      or Td unilaterally before bilateral vaccination with DCs pulsed with
      Cytomegalovirus phosphoprotein 65 (pp65) RNA. We and other laboratories have
      shown that pp65 is expressed in more than 90% of glioblastoma specimens but not
      in surrounding normal brain, providing an unparalleled opportunity to subvert
      this viral protein as a tumour-specific target. Patients given Td had enhanced DC
      migration bilaterally and significantly improved survival. In mice, Td pre
      conditioning also enhanced bilateral DC migration and suppressed tumour growth in
      a manner dependent on the chemokine CCL3. Our clinical studies and corroborating
      investigations in mice suggest that pre-conditioning with a potent recall antigen
      may represent a viable strategy to improve anti-tumour immunotherapy. 

PMID- 25762144
TI  - Cooperative insertion of CO2 in diamine-appended metal-organic frameworks.
AB  - The process of carbon capture and sequestration has been proposed as a method of
      mitigating the build-up of greenhouse gases in the atmosphere. If implemented,
      the cost of electricity generated by a fossil fuel-burning power plant would rise
      substantially, owing to the expense of removing CO2 from the effluent stream.
      There is therefore an urgent need for more efficient gas separation technologies,
      such as those potentially offered by advanced solid adsorbents. Here we show that
      diamine-appended metal-organic frameworks can behave as 'phase-change'
      adsorbents, with unusual step-shaped CO2 adsorption isotherms that shift markedly
      with temperature. Results from spectroscopic, diffraction and computational
      studies show that the origin of the sharp adsorption step is an unprecedented
      cooperative process in which, above a metal-dependent threshold pressure, CO2
      molecules insert into metal-amine bonds, inducing a reorganization of the amines
      into well-ordered chains of ammonium carbamate. As a consequence, large CO2
      separation capacities can be achieved with small temperature swings, and
      regeneration energies appreciably lower than achievable with state-of-the-art
      aqueous amine solutions become feasible. The results provide a mechanistic
      framework for designing highly efficient adsorbents for removing CO2 from various
      gas mixtures, and yield insights into the conservation of Mg(2+) within the
      ribulose-1,5-bisphosphate carboxylase/oxygenase family of enzymes. 

PMID- 25762145
TI  - Anomalocaridid trunk limb homology revealed by a giant filter-feeder with paired
      flaps.
AB  - Exceptionally preserved fossils from the Palaeozoic era provide crucial insights
      into arthropod evolution, with recent discoveries bringing phylogeny and
      character homology into sharp focus. Integral to such studies are
      anomalocaridids, a clade of stem arthropods whose remarkable morphology
      illuminates early arthropod relationships and Cambrian ecology. Although recent
      work has focused on the anomalocaridid head, the nature of their trunk has been
      debated widely. Here we describe new anomalocaridid specimens from the Early
      Ordovician Fezouata Biota of Morocco, which not only show well-preserved head
      appendages providing key ecological data, but also elucidate the nature of
      anomalocaridid trunk flaps, resolving their homology with arthropod trunk limbs.
      The new material shows that each trunk segment bears a separate dorsal and
      ventral pair of flaps, with a series of setal blades attached at the base of the
      dorsal flaps. Comparisons with other stem lineage arthropods indicate that
      anomalocaridid ventral flaps are homologous with lobopodous walking limbs and the
      endopod of the euarthropod biramous limb, whereas the dorsal flaps and associated
      setal blades are homologous with the flaps of gilled lobopodians (for example,
      Kerygmachela kierkegaardi, Pambdelurion whittingtoni) and exites of the 'Cambrian
      biramous limb'. This evidence shows that anomalocaridids represent a stage before
      the fusion of exite and endopod into the 'Cambrian biramous limb', confirming
      their basal placement in the euarthropod stem, rather than in the arthropod crown
      or with cycloneuralian worms. Unlike other anomalocaridids, the Fezouata taxon
      combines head appendages convergently adapted for filter-feeding with an
      unprecedented body length exceeding 2 m, indicating a new direction in the
      feeding ecology of the clade. The evolution of giant filter-feeding
      anomalocaridids may reflect the establishment of highly developed planktic
      ecosystems during the Great Ordovician Biodiversification Event. 

PMID- 25762146
TI  - Vapour-mediated sensing and motility in two-component droplets.
AB  - Controlling the wetting behaviour of liquids on surfaces is important for a
      variety of industrial applications such as water-repellent coatings and
      lubrication. Liquid behaviour on a surface can range from complete spreading, as
      in the 'tears of wine' effect, to minimal wetting as observed on a
      superhydrophobic lotus leaf. Controlling droplet movement is important in
      microfluidic liquid handling, on self-cleaning surfaces and in heat transfer.
      Droplet motion can be achieved by gradients of surface energy. However, existing
      techniques require either a large gradient or a carefully prepared surface to
      overcome the effects of contact line pinning, which usually limit droplet motion.
      Here we show that two-component droplets of well-chosen miscible liquids such as
      propylene glycol and water deposited on clean glass are not subject to pinning
      and cause the motion of neighbouring droplets over a distance. Unlike the
      canonical predictions for these liquids on a high-energy surface, these droplets
      do not spread completely but exhibit an apparent contact angle. We demonstrate
      experimentally and analytically that these droplets are stabilized by evaporation
      induced surface tension gradients and that they move in response to the vapour
      emitted by neighbouring droplets. Our fundamental understanding of this robust
      system enabled us to construct a wide variety of autonomous fluidic machines out
      of everyday materials. 

PMID- 25762140
TI  - Dissemination, divergence and establishment of H7N9 influenza viruses in China.
AB  - Since 2013 the occurrence of human infections by a novel avian H7N9 influenza
      virus in China has demonstrated the continuing threat posed by zoonotic
      pathogens. Although the first outbreak wave that was centred on eastern China was
      seemingly averted, human infections recurred in October 2013 (refs 3-7). It is
      unclear how the H7N9 virus re-emerged and how it will develop further;
      potentially it may become a long-term threat to public health. Here we show that
      H7N9 viruses have spread from eastern to southern China and become persistent in
      chickens, which has led to the establishment of multiple regionally distinct
      lineages with different reassortant genotypes. Repeated introductions of viruses
      from Zhejiang to other provinces and the presence of H7N9 viruses at live poultry
      markets have fuelled the recurrence of human infections. This rapid expansion of
      the geographical distribution and genetic diversity of the H7N9 viruses poses a
      direct challenge to current disease control systems. Our results also suggest
      that H7N9 viruses have become enzootic in China and may spread beyond the region,
      following the pattern previously observed with H5N1 and H9N2 influenza viruses.

PMID- 25762147
TI  - Materials chemistry: cooperative carbon capture.

PMID- 25762149
TI  - Current UK practices in steroid treatment of chronic lung disease.

PMID- 25762148
TI  - Presynaptic c-Jun N-terminal Kinase 2 regulates NMDA receptor-dependent glutamate
      release.
AB  - Activation of c-Jun N-terminal kinase (JNK) signaling pathway is a critical step
      for neuronal death occurring in several neurological conditions. JNKs can be
      activated via receptor tyrosine kinases, cytokine receptors, G-protein coupled
      receptors and ligand-gated ion channels, including the NMDA glutamate receptors.
      While JNK has been generally associated with postsynaptic NMDA receptors, its
      presynaptic role remains largely unexplored. Here, by means of biochemical,
      morphological and functional approaches, we demonstrate that JNK and its scaffold
      protein JIP1 are also expressed at the presynaptic level and that the NMDA-evoked
      glutamate release is controlled by presynaptic JNK-JIP1 interaction. Moreover,
      using knockout mice for single JNK isoforms, we proved that JNK2 is the essential
      isoform in mediating this presynaptic event. Overall the present findings unveil
      a novel JNK2 localization and function, which is likely to play a role in
      different physiological and pathological conditions. 

PMID- 25762150
TI  - Lateral trunk lean in pitchers affects both ball velocity and upper extremity
      joint moments.
AB  - BACKGROUND: The incidence of upper extremity injuries in baseball pitchers is
      increasing. Over the past decade there has been a great deal of research
      attempting to elucidate the cause of these injuries, focusing mainly on the
      mechanics of the pitching arm with no examination of other key segments, such as
      the trunk. This is surprising, as coaches will often comment on trunk position in
      an effort to improve pitching outcomes. PURPOSE: To determine the association
      between contralateral trunk lean and ball velocity and the moments about the
      elbow and glenohumeral joint. STUDY DESIGN: Descriptive laboratory study.
      METHODS: A total of 99 pitchers were recruited for this study and underwent a
      pitching analysis using 3-dimensional motion analysis techniques. A random
      intercept mixed-effects regression model was used to determine if statistically
      significant associations existed between contralateral trunk lean (away from the
      pitching arm side) and ball velocity, as well as the elbow varus moment and
      glenohumeral internal rotation moment. RESULTS: The results demonstrated that the
      greatest contralateral trunk lean occurs around the time of the peak elbow varus
      moment. Statistically significant associations were found between contralateral
      trunk lean and increased ball velocity (P=.003) indicating that for every 10
      degrees  increase in contralateral lean, ball velocity increased 0.5 m/s. Results
      also indicated that for every 10 degrees  increase in contralateral lean, elbow
      varus moments increased by 3.7 N.m and glenohumeral internal rotation moments
      increased by 2.5 N.m (P<.001 for both). CONCLUSION: Study findings indicate that
      the positioning of the trunk plays a substantial role in pitching performance and
      pitcher injury potential. This work helps to demonstrate the importance of proper
      trunk mechanics in pitching and highlights the need for future research to
      understand the contribution of the trunk to pitching mechanics. CLINICAL
      RELEVANCE: Pitching coaches and trainers can use the results of this study to
      stress the importance of proper trunk mechanics in pitching. Specifically,
      improving core strength and trunk control in an effort to maintain a more upright
      posture through the pitching cycle can reduce upper extremity joint stresses.

PMID- 25762154
TI  - Umbilical reconstruction in children: a simplified operative technique.
AB  - The umbilicus has a paramount aesthetical function for the abdomen and when
      removed due to a surgical procedure, an umbilicoplasty is mandatory: indeed, its
      absence could contribute to the development of psychological disorders,
      especially in childhood. Herein, we describe a straightforward technique to
      obtain a seemingly natural umbilical scar. This technique, easily taught in a
      general pediatric surgery environment, may be amenable for any kind of umbilical
      reconstruction. LEVEL OF EVIDENCE IV: This journal requires that authors assign a
      level of evidence to each article. For a full description of these Evidence-Based
      Medicine ratings, please refer to the Table of Contents or the online
      Instructions to Authors www.springer.com/00266 .

PMID- 25762153
TI  - Mass spectrometry and theoretical studies on N-C bond cleavages in the N
      sulfonylamidino thymine derivatives.
AB  - The reactivity of new biologically active thymine derivatives substituted with 2
      (arylsulfonamidino)ethyl group at N1 and N3 position was investigated in the gas
      phase using CID experiments (ESI-MS/MS) and by density functional theory (DFT)
      calculations. Both derivatives show similar chemistry in the negative mode with a
      retro-Michael addition (Path A(-)) being the most abundant reaction channel,
      which correlate well with the fluoride induced retro-Michael addition observed in
      solution. The difference in the fragmentation of N-3 substituted thymine 5 and N
      1 substituted thymine 1 in the positive mode relates to the preferred cleavage of
      the sulfonyl group (m/z 155, Path B) in N-3 isomer and the formation of the acryl
      sulfonamidine 3 (m/z 309) via Path A in N-1 isomer. Mechanistic studies of the
      cleavage reaction conducted by DFT calculations give the trend of the calculated
      activation energies that agree well with the experimental observations. A
      mechanism of the retro-Michael reaction was interpreted as a McLafferty type of
      fragmentation, which includes Hbeta proton shift to one of the neighboring oxygen
      atoms in a 1,5-fashion inducing N1(N3)-Calpha bond scission. This mechanism was
      found to be kinetically favorable over other tested mechanisms. Significant
      difference in the observed fragmentation pattern of N-1 and N-3 isomers proves
      the ESI-MS/MS technique as an excellent method for tracking the fate of similar
      sulfonamidine drugs. Also, the observed N-1 and/or N-3 thymine alkylation with in
      situ formed reactive acryl sulfonamidine 3 as a Michael acceptor may open
      interesting possibilities for the preparation of other N-3 substituted
      pyrimidines. 

PMID- 25762155
TI  - A cysteine residue affects the conformational state and neuronal toxicity of
      mutant SOD1 in mice: relevance to the pathogenesis of ALS.
AB  - We previously showed by in vitro experiments that the cysteine residue (Cys111)
      near the dimer interface is critical for monomerization and resultant aggregate
      formation of mutant Cu, Zn-superoxide dismutase (SOD1) protein, which is toxic to
      motor neurons in familial amyotrophic lateral sclerosis (ALS). To verify the
      importance of Cys111 in the mutant SOD1-associated ALS pathogenesis in vivo, we
      analyzed the disease phenotype of SOD1 transgenic mice harboring H46R mutation
      alone (H46R mice) or H46R/C111S double mutations (H46R/C111S mice). Behavioral,
      histological and biochemical analyses of the spinal cord showed that the onset
      and progression of the disease phenotype were delayed in H46R/C111S mice compared
      with H46R mice. We found that peroxidized Cys111 of H46R SOD1 plays a role in
      promoting formation of high molecular weight insoluble SOD1 species that is
      correlated with the progression of the motor neuron disease phenotype. These
      results support that Cys111 is a critical residue for the neuronal toxicity of
      mutant SOD1 in vivo, and the blockage of peroxidation of this residue in mutant
      SOD1 may constitute a future target for developing ALS treatment. 

PMID- 25762157
TI  - The prevalence of frailty and related factors in community-dwelling Turkish
      elderly according to modified Fried Frailty Index and FRAIL scales.
AB  - AIM: The purpose of this study is to determine the prevalence of frailty with the
      Fried Frailty Index (FFI) and FRAIL scales (Fatigue, Resistance, Ambulation,
      Illness, Low weight) and also its associated factors in the community-dwelling
      Turkish elderly. METHODS: This is a cross-sectional population-based study in an
      urban area with a population of over 1,200,000. We sampled 1/100 of the elderly
      population. Frailty prevalence was assessed with a modified version of the FFI
      and FRAIL scale. Nutritional status was assessed by Mini Nutritional Assessment.
      Cognitive function was assessed by Mini-Mental State Examination. Depressive mood
      was assessed by GDS. Functional capacity was assessed by the instrumental
      activities of daily living scale. Falls and fear of falling were noted. Uni- and
      multivariate analyses were done to determine associated factors for frailty.
      RESULTS: A total of 906 community-dwelling elderly were included, in whom the
      mean age and standard deviation (SD) of age were 71.5 (5.6) years (50.6 %
      female). We detected frailty (female 30.4 %, male 25.2 %), pre-frailty and non
      frailty prevalence with FFI as 27.8, 34.8, and 37.4 %, respectively. The
      prevalence of frailty (female 14.5 %, male 5.4 %), pre-frailty and non-frailty
      with the FRAIL scale was detected as 10, 45.6, and 44.4 %. Coexisting associated
      factors related with frailty in both models were found as depressive mood,
      cognitive impairment, and malnutrition in multivariate analysis. CONCLUSIONS:
      According to both scales, frailty was strongly associated with cognitive
      impairment, depressive mood, and malnutrition in the community-dwelling Turkish
      elderly population.

PMID- 25762158
TI  - Influence of repeated effort induced by a 6-min walk test on postural response in
      older sedentary women.
AB  - According to the latest recommendations, adults should exercise regularly at
      moderate intensity to improve aerobic fitness and body composition. However, it
      is unknown whether aerobic exercise at submaximal intensity has detrimental
      effects on balance in older sedentary adults. We explored the effects of two 6
      min walk tests (6MWTs) on the postural responses in 49 sedentary women between 60
      and 76 years old. We assumed that an increase in the center of pressure (COP)
      fluctuations or a loss in the complexity of the COP time series would be a sign
      of a deleterious effect on balance. We used kinematic stabilometric parameters,
      recurrence quantification analysis (RQA) and the central tendency measure (CTM).
      We refer to the measures obtained through RQA and CTM methods by dynamical
      measures. Repeated-measures analysis of variance showed no significant
      differences between the three sets of postural kinematic measures (before vs.
      after the first vs. after the second 6MWT). However, we observed significant
      differences between the three sets for the CTM measure in the antero-posterior
      direction (p < 0.002), RQA determinism in the medio-lateral (ML) direction (p <
      0.0001), and RQA entropy in the ML direction (F = 5.93; p < 0.004).Our results
      indicate that the effects of moderate-intensity walking exercise on posture are
      not revealed by classical postural kinematic measures but only by dynamical
      measures. The loss of complexity in the COP time series observed after both the
      first and second 6MWTs may indicate presymptomatic deterioration in the postural
      adaptive capabilities of sedentary older women. 

PMID- 25762156
TI  - Genetics of CD33 in Alzheimer's disease and acute myeloid leukemia.
AB  - The CD33 single-nucleotide polymorphism (SNP) rs3865444 has been associated with
      the risk of Alzheimer's disease (AD). Rs3865444 is in linkage disequilibrium with
      rs12459419 which has been associated with efficacy of an acute myeloid leukemia
      (AML) chemotherapeutic agent based on a CD33 antibody. We seek to evaluate the
      extent to which CD33 genetics in AD and AML can inform one another and advance
      human disease therapy. We have previously shown that these SNPs are associated
      with skipping of CD33 exon 2 in brain mRNA. Here, we report that these CD33 SNPs
      are associated with exon 2 skipping in leukocytes from AML patients and with a
      novel CD33 splice variant that retains CD33 intron 1. Each copy of the minor
      rs12459419T allele decreases prototypic full-length CD33 expression by ~ 25% and
      decreases the AD odds ratio by ~ 0.10. These results suggest that CD33
      antagonists may be useful in reducing AD risk. CD33 inhibitors may include
      humanized CD33 antibodies such as lintuzumab which was safe but ineffective in
      AML clinical trials. Here, we report that lintuzumab downregulates cell-surface
      CD33 by 80% in phorbol-ester differentiated U937 cells, at concentrations as low
      as 10 ng/ml. Overall, we propose a model wherein a modest effect on RNA splicing
      is sufficient to mediate the CD33 association with AD risk and suggest the
      potential for an anti-CD33 antibody as an AD-relevant pharmacologic agent.

PMID- 25762159
TI  - Are andropause symptoms related to depression?
AB  - BACKGROUND: Andropause is a middle-age condition in which men experience changes
      in their physical, spiritual and emotional health. The association between
      andropause and psychological symptoms such as depression are not very clear yet.
      AIMS: The objective of this study was therefore to determine the association
      between the 'Aging Males Symptoms Scale' (AMS) and depression. METHODS: A cross
      sectional study was conducted among 521 old men. To collect data, the AMS and the
      Patient Health Questionnaires 2 and 9 were used to screen depression, in addition
      to questions on background and fertility. Multiple linear regression analysis was
      used to assess the association between andropause symptoms and depression.
      RESULTS: Based on our results and the AMS score, 51.5% of the study population
      had clinical symptoms of androgen disorder, 3.7% of which had severe symptoms.
      There was a strong correlation between the AMS score and depression. Depression,
      diabetes, cigarette smoking and spousal age retained their significant
      associations even after entering the relevant demographic, anthropometric,
      smoking and disease variables in the multivariable model. As a positive
      predictive factor, depression had the strongest association with AMS.
      CONCLUSIONS: Based on our results, there is a direct association between
      andropause symptoms and depression, where the increasing AMS score corresponds
      with the severity of depression. DISCUSSION: Our results show the need of
      screening for depression when evaluating andropause symptoms.

PMID- 25762160
TI  - Lokomat training in vascular dementia: motor improvement and beyond!
AB  - Vascular dementia (VaD) is a general term describing problems with reasoning,
      planning, judgment, memory, and other thought processes caused by brain damage
      from impaired blood flow to the brain. Cognitive rehabilitation and physical
      therapy are the mainstays of dementia treatment, although often ineffective
      because of the scarce collaboration of the patients. However, emerging data
      suggest that physical activity may reduce the risk of cognitive impairment,
      mainly VaD, in older people living independently. Herein, we describe a 72-year
      old male affected by VaD, in which traditional cognitive training in addition to
      intensive gait robotic rehabilitation (by using Lokomat device) led to a
      significant improvement in the motor and cognitive function. This promising
      finding may be related either to the intensive and repetitive aerobic exercises
      or to the task-oriented training with computerized visual feedback, which can be
      considered as a relevant tool to increase patients' motor output, involvement,
      and motivation during robotic training. 

PMID- 25762161
TI  - Analgesic and anti-inflammatory activities of Citrus aurantium L. blossoms
      essential oil (neroli): involvement of the nitric oxide/cyclic-guanosine
      monophosphate pathway.
AB  - The analgesic and anti-inflammatory properties of Citrus aurantium L. blossoms
      essential oil (neroli) were investigated in mice and rats. The analgesic activity
      of neroli was assessed by acetic acid-induced writhing and Eddy's hot plate
      methods, while acute and chronic anti-inflammatory effects were investigated by
      inflammatory paw edema in rat and the cotton pellet-induced granuloma tissue
      model, respectively. Mechanistic studies were conducted using L-nitro arginine
      methyl ester (L-NAME), an inhibitor of NO synthase. Neroli significantly
      decreased the number of acetic acid-induced writhes in mice compared to 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 neroli (especially at 40 mg/kg) was found to be very close
      to the standard drug, diclofenac sodium (50 mg/kg). In cotton pellet-induced
      granuloma, neroli was effective regarding the transudate and granuloma formation
      amount. Neroli was analyzed by gas chromatography (GC) and gas chromatography
      mass spectrometry (GC-MS) and twenty-three constituents, representing 91.0 % of
      the oil, were identified. The major components of neroli were characterized as
      linalool (28.5 %), linalyl acetate (19.6 %), nerolidol (9.1 %), E,E-farnesol (9.1
      %), alpha-terpineol (4.9 %), and limonene (4.6 %), which might be responsible for
      these observed activities. The results suggest that neroli possesses biologically
      active constituent(s) that have significant activity against acute and especially
      chronic inflammation, and have central and peripheral antinociceptive effects
      which support the ethnomedicinal claims of the use of the plant in the management
      of pain and inflammation. 

PMID- 25762162
TI  - Use of yeast cell wall extract as a tool to reduce the impact of necrotic
      enteritis in broilers.
AB  - The use of a yeast cell wall extract derived from Saccharomyces cerevisiae
      (Actigen((r))) has been proposed as an alternative to in-feed antibiotics. This
      experiment was conducted to investigate the efficacy of yeast cell extract as an
      alternative to zinc bacitracin or salinomycin using a necrotic enteritis
      challenge model. A feeding study was conducted using 480-day-old male Ross 308
      chicks assigned to 48 floor pens. A 2 * 4 factorial arrangement of treatments was
      employed. The factors were: challenge (- or +) and feed additive (control, zinc
      bacitracin at 100/50 mg/kg, yeast cell wall extract at 400/800/200 mg/kg, or
      salinomycin at 60 mg/kg in starter, grower, and finisher, respectively). Diets
      based on wheat, sorghum, soybean meal, meat and bone meal, and canola meal were
      formulated according to the Ross 308 nutrient specifications. Birds were
      challenged using a previously established protocol (attenuated Eimeria spp
      oocysts) on d 9 and 10(8) to 10(9) Clostridium perfringens (type A strain EHE
      NE18) on d 14 and 15). Challenged and unchallenged birds were partitioned to
      avoid cross contamination. Challenged birds had lower weight gain, feed intake
      and livability compared to unchallenged birds on d 24 and d 35 (P < 0.05). Birds
      given zinc bacitracin, yeast cell wall extract, or salinomycin had improved
      weight gain and livability when compared to control birds given no additives.
      Challenge * additive interactions were observed for feed intake and weight gain
      on d 24 and d 35 (P < 0.01). The additives all had a greater positive impact on
      feed intake, weight gain, and livability in challenged than unchallenged birds.
      All challenged birds showed higher necrotic enteritis lesion scores in the small
      intestine sections when compared to unchallenged birds (P < 0.01). Birds fed
      yeast cell wall extract exhibited increased villus height, decreased crypt depth,
      and increased villus:crypt ratio when challenged. Yeast cell wall extract, zinc
      bacitracin, and salinomycin were effective in preventing performance decline from
      necrotic enteritis in the current study. This study indicates that yeast cell
      wall extract has promise as a tool for controlling necrotic enteritis. 

PMID- 25762163
TI  - Downregulation of basic fibroblast growth factor is associated with femoral head
      necrosis in broilers.
AB  - Femoral head necrosis (FHN) is a metabolic cartilage disease of rapidly growing
      broilers. The aim of the present study was to investigate the role of basic
      fibroblast growth factor (bFGF) in the apoptotic processes associated with FHN.
      Broilers were selected and categorized based on clinical examination in 3 groups:
      healthy, femoral head separation, or femoral head separation with growth plate
      lacerations. Hematoxylin and eosin staining showed fewer chondrocytes in the
      resting zone of the growth plates when FHN occurred. Moreover, the terminal
      deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay revealed a
      significant increase in chondrocyte apoptosis. Furthermore, immunohistochemical
      assays and real-time quantitative PCR analysis demonstrated a decline in bFGF
      expression. In addition, reduced Bcl-2 mRNA expression was observed along with a
      corresponding increase in Bax and caspase-3 mRNA expression in FHN samples. There
      was a correlation between bFGF protein expression and the proportion of TUNEL
      positive cells and a correlation between bFGF mRNA expression and expression of
      Bax, and caspase-3. The results of the study suggested that the expression of
      bFGF was reduced in the process of chondrocyte apoptosis, which could play an
      important role in the pathogenesis of FHN in chickens. 

PMID- 25762164
TI  - Functions of plastid protein import and the ubiquitin-proteasome system in
      plastid development.
AB  - Plastids, such as chloroplasts, are widely distributed endosymbiotic organelles
      in plants and algae. Apart from their well-known functions in photosynthesis,
      they have roles in processes as diverse as signal sensing, fruit ripening, and
      seed development. As most plastid proteins are produced in the cytosol, plastids
      have developed dedicated translocon machineries for protein import, comprising
      the TOC (translocon at the outer envelope membrane of chloroplasts) and TIC
      (translocon at the inner envelope membrane of chloroplasts) complexes. Multiple
      lines of evidence reveal that protein import via the TOC complex is actively
      regulated, based on the specific interplay between distinct receptor isoforms and
      diverse client proteins. In this review, we summarize recent advances in our
      understanding of protein import regulation, particularly in relation to control
      by the ubiquitin-proteasome system (UPS), and how such regulation changes plastid
      development. The diversity of plastid import receptors (and of corresponding
      preprotein substrates) has a determining role in plastid differentiation and
      interconversion. The controllable turnover of TOC components by the UPS
      influences the developmental fate of plastids, which is fundamentally linked to
      plant development. Understanding the mechanisms by which plastid protein import
      is controlled is critical to the development of breakthrough approaches to
      increase the yield, quality and stress tolerance of important crop plants, which
      are highly dependent on plastid development. This article is part of a Special
      Issue entitled: Chloroplast Biogenesis. 

PMID- 25762165
TI  - Effect of duloxetine in Japanese patients with chemotherapy-induced peripheral
      neuropathy: a pilot randomized trial.
AB  - BACKGROUND: Chemotherapy-induced peripheral neuropathy (CIPN) is difficult to
      manage. A phase III trial conducted in the United States demonstrated that
      duloxetine was effective for CIPN caused by taxane and platinum-based
      chemotherapy. No randomized trial of duloxetine for CIPN has been conducted in
      Japan. METHODS: In this open-label, randomized, crossover study, eligible
      patients were randomized to Group A or Group B. Group A received duloxetine 20
      mg/day orally for the first week and 40 mg/day for the next 3 weeks. Group B
      received vitamin B12 (VB12) 1.5 mg/day orally for 4 weeks. After a 2- to 4-week
      washout period, treatment was crossed over for another 4 weeks. The severity of
      numbness and pain was assessed using a visual analog scale (VAS). RESULTS: Thirty
      four patients were enrolled. Obvious decreases in the mean VAS scores for
      numbness and pain were observed for the periods of duloxetine administration.
      Significant differences were observed between the duloxetine-first (Group A) and
      the VB12-first (Group B) groups with respect to numbness (p = 0.03) and pain (p =
      0.04) at 4 weeks after administration. Fatigue was observed in six of the 34
      participants (17.6 %). CONCLUSIONS: Our data suggests that duloxetine has a
      beneficial effect on CIPN caused by oxaliplatin, paclitaxel, vincristine, or
      bortezomib in Japanese patients.

PMID- 25762166
TI  - Comparison of prognosis between patients with renal cell carcinoma on
      hemodialysis and those with renal cell carcinoma in the general population.
AB  - OBJECTIVE: We compared the clinical features and prognosis of renal cell
      carcinoma (RCC) between patients on hemodialysis (RCC-HD) and those in the
      general population (RCC-general). METHODS: We included a total of 1,794 patients
      who underwent surgery (RCC-HD, 408; RCC-general, 1,386) and analyzed the clinical
      characteristics and oncological outcomes using a stage-for-stage analysis between
      the two groups. RESULTS: In the RCC-HD group, the mean duration of dialysis
      before surgery was 120 months. Compared to the RCC-general group, the RCC-HD
      group tended to be younger (55 vs. 60 years, p < 0.0001) and more predominately
      male (84 % vs. 70 %, p < 0.0001), and the tumor size was smaller in this group
      (39 vs. 49 mm, p < 0.0001). The pathological characteristics of the RCC-HD group
      included a higher frequency of papillary tumors (22 % vs. 5 %, p < 0.0001) and
      stage I tumors (82 % vs. 68 %, p < 0.0001). During the follow-up period, 39 of
      patients (10 %) in the RCC-HD group and 193 patients (14 %) in the RCC-general
      group died of cancer. The patients on hemodialysis had better cancer-specific
      survival (CSS) than their counterparts (p = 0.0292) in the univariable analysis,
      but no significance was found in the multivariable analysis. In the stage-for
      stage analysis, the 5-year CSS was similar between the two groups for each stage.
      CONCLUSIONS: CSS appeared to be better in the RCC-HD group than in the RCC
      general group, which may be associated with the higher incidence of stage I
      disease in the RCC-HD group. The comparable CSS between the groups in the stage
      for-stage analysis supports this finding.

PMID- 25762167
TI  - Erratum to: Prognostic value of regulatory T cells in newly diagnosed chronic
      myeloid leukemia patients.

PMID- 25762168
TI  - Oncological benefit of primary tumor resection with high tie lymph node
      dissection in unresectable colorectal cancer with synchronous peritoneal
      metastasis: a propensity score analysis of data from a multi-institute database.
AB  - BACKGROUND: Peritoneal metastasis is recognized as a predictor of poor prognosis
      in patients with colorectal cancer, and whether surgical intervention for
      peritoneal metastasis has any clinical benefit has remained controversial. The
      purposes of this study were to identify prognostic factors in cases of
      unresectable colorectal cancer with synchronous peritoneal metastasis and to
      clarify the impacts of primary tumor resection with high tie lymph node
      dissection. METHODS: A multi-institutional retrospective analysis was conducted
      of 579 patients who underwent resection of the primary tumor for unresectable
      colorectal cancer with peritoneal metastasis between 1991 and 2007. For these 579
      patients, clinicopathological variables were analyzed for prognostic significance
      using Cox proportional hazards model and propensity score analysis to mitigate
      the selection bias. RESULTS: Multivariate analysis revealed hematogenous
      metastasis (p < 0.001), histology of the tumor (p = 0.006), postoperative
      chemotherapy (p < 0.001), and lymph node dissection (p = 0.001) as independent
      prognostic factors. In the propensity-matched cohort, patients treated with high
      tie lymph node dissection showed a significantly better overall survival than
      those with low tie lymph node dissection (median overall survival 13.0 vs. 11.5
      months; p = 0.041). CONCLUSIONS: It is suggested that primary tumor resection
      with high tie lymph node dissection favorably affects survival, even in
      unresectable colorectal cancer with peritoneal metastasis.

PMID- 25762169
TI  - Conjoined unification venoplasty for graft double portal vein branches as a
      modification of autologous Y-graft interposition.

PMID- 25762170
TI  - Postmenopausal hormone therapy and the risk of rheumatoid arthritis: results from
      the Swedish EIRA population-based case-control study.
AB  - To study the association between postmenopausal hormone therapy (PMH) use and the
      risk of rheumatoid arthritis (RA) stratifying the cases by the presence/absence
      of antibodies against citrullinated peptides (ACPA). A subset of the
      Epidemiological Investigation of RA (EIRA), a population-based case-control
      study, comprising postmenopausal women aged 50-70 living in Sweden, between 2006
      and 2011 was analysed (523 cases and 1057 controls). All participants answered an
      extensive questionnaire, including questions regarding PMH use and potential
      confounders (education, smoking, BMI, oral contraceptives, reproductive factors).
      We calculated odds ratios (OR) of developing ACPA-positive/-negative RA, with 95%
      confidence intervals (CI) and adjusted for age, residential area and smoking.
      Current users of PMH had a decreased risk of ACPA-positive RA compared with never
      users (OR 0.6, 95% CI 0.3-0.9). The decreased risk was observed mainly in the age
      group 50-59 years (OR 0.3, 95% CI 0.1-0.8) but not in the age-group 60-70 years
      (OR 0.8, 95% CI 0.4-1.4). Among current users of a combined therapy (estrogen
      plus progestogens) an OR of 0.3 (95% CI 0.1-0.7) of ACPA-positive RA was
      observed, while no significant association was found among women who used
      estrogen only (OR 0.8, 95% CI 0.5-1.6). No association between PMH use and ACPA
      negative RA was found. PMH use might reduce the risk of ACPA-positive RA in post
      menopausal women over 50 years of age, but not of ACPA-negative RA. The negative
      influence of this treatment on the risk of other chronic conditions cannot be
      overlooked.

PMID- 25762171
TI  - Control selection methods in recent case-control studies conducted as part of
      infectious disease outbreaks.
AB  - Successful investigation of national outbreaks of communicable disease relies on
      rapid identification of the source. Case-control methodologies are commonly used
      to achieve this. We assessed control selection methods used in recently published
      case-control studies for methodological and resource issues to determine if a
      standard approach could be identified. Neighbourhood controls were the most
      frequently used method in 53 studies of a range of different sizes, infections
      and settings. The most commonly used method of data collection was face to face
      interview. Control selection issues were identified in four areas: method of
      identification of controls, appropriateness of controls, ease of recruitment of
      controls, and resource requirements. Potential biases arising from the method of
      control selection were identified in half of the studies assessed. There is a
      need to develop new ways of selecting controls in a rapid, random and
      representative manner to improve the accuracy and timeliness of epidemiological
      investigations and maximise the effectiveness of public health interventions.
      Innovative methods such as prior recruitment of controls could improve timeliness
      and representativeness of control selection. 

PMID- 25762172
TI  - The association between serum 25-hydroxyvitamin D3 concentration and risk of
      disease death in men: modification by magnesium intake.
AB  - Low vitamin D status increases the risk of death. Magnesium plays an essential
      role in vitamin D metabolism and low magnesium intake may predispose to vitamin D
      deficiency and potentiate the health problems. We investigated whether magnesium
      intake modifies the serum 25(OH)D3 concentration and its associations with
      mortality in middle-aged and older men. We included 1892 men aged 42-60 years
      without cardiovascular disease or cancer at baseline in 1984-1989 from the
      prospective, population-based Kuopio Ischaemic Heart Disease Risk Factor Study.
      Serum 25(OH)D3 was measured with the high-performance liquid chromatography using
      coulometric electrode array detection. Magnesium intake was assessed with 4-day
      food recording. Deaths were ascertained by a computer linkage to the national
      cause of death register. Deaths due accidents and suicides were excluded. Cox
      proportional hazards regression models were used to analyze the associations. The
      multivariate-adjusted hazard ratio (HR) for death in the lowest (<32.1 nmol/L)
      versus the highest (>49.4 nmol/L) serum 25(OH)D3 tertile was 1.31 (95 % CI 1.07
      1.60, Ptrend = 0.01). Stratified by the magnesium intake, the higher risk was
      observed only in the lower magnesium intake median (<414 mg/day); HR = 1.60 (95 %
      CI 1.19-2.13, Ptrend = 0.002) in the lowest versus the highest 25(OH)D3 tertile,
      whereas the corresponding HR = 1.07, 95 % CI 0.75-1.36, Ptrend = 0.63) in the
      higher magnesium intake median, P for interaction = 0.08. In this cohort of
      middle-aged and older men low serum 25(OH)D3 concentration was associated with
      increased risk of death mainly in those with lower magnesium intake.

PMID- 25762173
TI  - Challenges in conducting genome-wide association studies in highly admixed multi
      ethnic populations: the Generation R Study.
AB  - Genome-wide association studies (GWAS) have been successful in identifying loci
      associated with a wide range of complex human traits and diseases. Up to now, the
      majority of GWAS have focused on European populations. However, the inclusion of
      other ethnic groups as well as admixed populations in GWAS studies is rapidly
      rising following the pressing need to extrapolate findings to non-European
      populations and to increase statistical power. In this paper, we describe the
      methodological steps surrounding genetic data generation, quality control, study
      design and analytical procedures needed to run GWAS in the multiethnic and highly
      admixed Generation R Study, a large prospective birth cohort in Rotterdam, the
      Netherlands. Furthermore, we highlight a number of practical considerations and
      alternatives pertinent to the quality control and analysis of admixed GWAS data.

PMID- 25762174
TI  - Making sense of hematopoietic stem cell niches.
AB  - The hematopoietic stem cell (HSC) niche commonly refers to the pairing of
      hematopoietic and mesenchymal cell populations that regulate HSC self-renewal,
      differentiation, and proliferation. Anatomic localization of the niche is a
      dynamic unit from the developmental stage that allows proliferating HSCs to
      expand before they reach the bone marrow where they adopt a quiescent phenotype
      that protects their integrity and functions. Recent studies have sought to
      clarify the complexity behind the HSC niche by assessing the contributions of
      specific cell populations to HSC maintenance. In particular, perivascular
      microenvironments in the bone marrow confer distinct vascular niches that
      regulate HSC quiescence and the supply of lineage-committed progenitors. Here, we
      review recent data on the cellular constituents and molecular mechanisms involved
      in the communication between HSCs and putative niches. 

PMID- 25762175
TI  - Hematopoietic stem cells: concepts, definitions, and the new reality.
AB  - Hematopoietic stem cell (HSC) research took hold in the 1950s with the
      demonstration that intravenously injected bone marrow cells can rescue irradiated
      mice from lethality by reestablishing blood cell production. Attempts to quantify
      the cells responsible led to the discovery of serially transplantable, donor
      derived, macroscopic, multilineage colonies detectable on the spleen surface 1 to
      2 weeks posttransplant. The concept of self-renewing multipotent HSCs was born,
      but accompanied by perplexing evidence of great variability in the outcomes of
      HSC self-renewal divisions. The next 60 years saw an explosion in the development
      and use of more refined tools for assessing the behavior of prospectively
      purified subsets of hematopoietic cells with blood cell-producing capacity. These
      developments have led to the formulation of increasingly complex hierarchical
      models of hematopoiesis and a growing list of intrinsic and extrinsic elements
      that regulate HSC cycling status, viability, self-renewal, and lineage outputs.
      More recent examination of these properties in individual, highly purified HSCs
      and analyses of their perpetuation in clonally generated progeny HSCs have now
      provided definitive evidence of linearly transmitted heterogeneity in HSC states.
      These results anticipate the need and use of emerging new technologies to
      establish models that will accommodate such pluralistic features of HSCs and
      their control mechanisms. 

PMID- 25762176
TI  - Xenograft models for normal and malignant stem cells.
AB  - The model systems available for studying human hematopoiesis, malignant
      hematopoiesis, and hematopoietic stem cell (HSC) function in vivo have improved
      dramatically over the last decade, primarily due to improvements in xenograft
      mouse strains. Several recent reviews have focused on the historic development of
      immunodeficient mice over the last 2 decades, as well as their use in
      understanding human HSC and leukemia stem cell (LSC) biology and function in the
      context of a humanized mouse. However, in the intervening time since these
      reviews, a number of new mouse models, technical approaches, and scientific
      advances have been made. In this review, we update the reader on the newest and
      best models and approaches available for studying human malignant and normal HSCs
      in immunodeficient mice, including newly developed mice for use in chemotherapy
      testing and improved techniques for humanizing mice without laborious
      purification of HSC. We also review some relevant scientific findings from
      xenograft studies and highlight the continued limitations that confront
      researchers working with human HSC and LSC in vivo. 

PMID- 25762178
TI  - Introduction to a review series on hematopoietic stem cells.

PMID- 25762179
TI  - Regulatory network control of blood stem cells.
AB  - Hematopoietic stem cells (HSCs) are characterized by their ability to execute a
      wide range of cell fate choices, including self-renewal, quiescence, and
      differentiation into the many different mature blood lineages. Cell fate decision
      making in HSCs, as indeed in other cell types, is driven by the interplay of
      external stimuli and intracellular regulatory programs. Given the pivotal nature
      of HSC decision making for both normal and aberrant hematopoiesis, substantial
      research efforts have been invested over the last few decades into deciphering
      some of the underlying mechanisms. Central to the intracellular decision making
      processes are transcription factor proteins and their interactions within gene
      regulatory networks. More than 50 transcription factors have been shown to affect
      the functionality of HSCs. However, much remains to be learned about the way in
      which individual factors are connected within wider regulatory networks, and how
      the topology of HSC regulatory networks might affect HSC function. Nevertheless,
      important progress has been made in recent years, and new emerging technologies
      suggest that the pace of progress is likely to accelerate. This review will
      introduce key concepts, provide an integrated view of selected recent studies,
      and conclude with an outlook on possible future directions for this field. 

PMID- 25762177
TI  - De novo generation of HSCs from somatic and pluripotent stem cell sources.
AB  - Generating human hematopoietic stem cells (HSCs) from autologous tissues, when
      coupled with genome editing technologies, is a promising approach for cellular
      transplantation therapy and for in vitro disease modeling, drug discovery, and
      toxicology studies. Human pluripotent stem cells (hPSCs) represent a potentially
      inexhaustible supply of autologous tissue; however, to date, directed
      differentiation from hPSCs has yielded hematopoietic cells that lack robust and
      sustained multilineage potential. Cellular reprogramming technologies represent
      an alternative platform for the de novo generation of HSCs via direct conversion
      from heterologous cell types. In this review, we discuss the latest advancements
      in HSC generation by directed differentiation from hPSCs or direct conversion
      from somatic cells, and highlight their applications in research and prospects
      for therapy. 

PMID- 25762180
TI  - Results of a phase 2 study of pacritinib (SB1518), a JAK2/JAK2(V617F) inhibitor,
      in patients with myelofibrosis.
AB  - Pacritinib (SB1518) is a Janus kinase 2 (JAK2), JAK2(V617F), and Fms-like
      tyrosine kinase 3 inhibitor that does not inhibit JAK1. It demonstrated a
      favorable safety profile with promising efficacy in phase 1 studies in patients
      with primary and secondary myelofibrosis (MF). This multicenter phase 2 study
      further characterized the safety and efficacy of pacritinib in the treatment of
      patients with MF. Eligible patients had clinical splenomegaly poorly controlled
      with standard therapies or were newly diagnosed with intermediate- or high-risk
      Lille score. Patients with any degree of cytopenia were eligible. Thirty-five
      patients were enrolled. At entry, 40% had hemoglobin <10 g/dL and 43% had
      platelets <100 000* 10(9)/L. Up to week 24, 8 of 26 evaluable patients (31%)
      achieved a >=35% decrease in spleen volume determined by magnetic resonance
      imaging and 14 of 33 (42%) attained a >=50% reduction in spleen size by physical
      examination. Median MF symptom improvement was >=50% for all symptoms except
      fatigue. Grade 1 or 2 diarrhea (69%) and nausea (49%) were the most common
      treatment-emergent adverse events. The study drug was discontinued in 9 patients
      (26%) due to adverse events (4 severe). Pacritinib is an active agent in patients
      with MF, offering a potential treatment option for patients with preexisting
      anemia and thrombocytopenia. This trial was registered at www.clinicaltrials.gov
      as #NCT00745550. 

PMID- 25762181
TI  - Current challenges in clinical development of "targeted therapies": the case of
      acute myeloid leukemia.
AB  - A fundamental difficulty in testing "targeted therapies" in acute myeloid
      leukemia (AML) is the limitations of preclinical models in capturing inter- and
      intrapatient genomic heterogeneity. Clinical trials typically focus on single
      agents despite the routine emergence of resistant subclones and experience in
      blast-phase chronic myeloid leukemia and acute promyelocytic leukemia arguing
      against this strategy. Inclusion of only relapsed-refractory, or unfit newly
      diagnosed, patients risks falsely negative results. There is uncertainty as to
      whether eligibility should require demonstration of the putative target and
      regarding therapeutic end points. Although use of in vivo preclinical models
      employing primary leukemic cells is first choice, newer preclinical models
      including "organoids" and combinations of pharmacologic and genetic approaches
      may better align models with human AML. We advocate earlier inclusion of
      combinations +/- chemotherapy and of newly diagnosed patients into clinical
      trials. When a drug plausibly targets a pathway uniquely related to a specific
      genetic aberration, eligibility should begin with this subset, including patients
      with other malignancies, with subsequent extension to other patients. In other
      cases, a more open-minded approach to initial eligibility would facilitate
      quicker identification of responsive subsets. Complete remission without minimal
      residual disease seems a particularly useful short-term end point. Genotypic and
      phenotypic studies should be prespecified and performed routinely to distinguish
      responders from nonresponders. 

PMID- 25762183
TI  - The Subjective Well-Being Method of Valuation: An Application to General Health
      Status.
AB  - OBJECTIVE: To introduce the subjective well-being (SWB) method of valuation and
      provide an example by valuing health status. The SWB method allows monetary
      valuations to be performed in the absence of market relationships. DATA SOURCES:
      Data are from the 1975-2010 General Social Survey. STUDY DESIGN: The value of
      health status is determined via the estimation of an implicit derivative based on
      a happiness equation. Two-stage least-squares was used to estimate happiness as a
      function of poor-to-fair health status, annual household income adjusted for
      household size, age, sex, race, marital status, education, year, and season. Poor
      to-fair health status and annual household income are instrumented using a proxy
      for intelligence, a temporal version of the classic distance instrument, and the
      average health status of individuals who are demographically similar but
      geographically separated. Instrument validity is evaluated. PRINCIPAL FINDINGS:
      Moving from good/excellent health to poor/fair health (1 year of lower health
      status) is equivalent to the loss of $41,654 of equivalized household income
      (2010 constant dollars) per annum, which is larger than median equivalized
      household income. CONCLUSION: The SWB method may be useful in making monetary
      valuations where fundamental market relationships are not present.

PMID- 25762182
TI  - Genetics of Bone Mass in Childhood and Adolescence: Effects of Sex and Maturation
      Interactions.
AB  - We aimed to determine if adult bone mineral density (BMD) susceptibility loci
      were associated with pediatric bone mass and density, and if sex and pubertal
      stage influenced any association. We analyzed prospective areal BMD (aBMD) and
      bone mineral content (BMC) data from the Bone Mineral Density in Childhood Study
      (n = 603, European ancestry, 54% female). Linear mixed models were used to assess
      if 77 single-nucleotide polymorphisms (SNPs) near known adult BMD susceptibility
      loci interacted with sex and pubertal stage to influence the aBMD/BMC; adjusting
      for age, BMI, physical activity, and dietary calcium. The strongest main
      association was observed between an SNP near C7orf58 and distal radius aBMD.
      However, this association had a significant sex * SNP interaction, revealing a
      significant association only in females (b = -0.32, p = 1.8 * 10(-6)).
      Furthermore, the C12orf23 locus had significant interactions with both sex and
      pubertal stage, revealing associations in females during Tanner stage I for total
      hip aBMD (b = 0.24, p = 0.001) and femoral neck aBMD (b = 0.27, p = 3.0 * 10(
      5)). In contrast, the sex * SNP interactions for loci near LRP5 and WNT16
      uncovered associations that were only in males for total body less head BMC (b =
      0.22, p = 4.4 * 10(-4)) and distal radius aBMD (b = 0.27, p = 0.001),
      respectively. Furthermore, the LRP5 locus interacted with both sex and pubertal
      stage, demonstrating associations that were exclusively in males during Tanner V
      for total hip aBMD (b = 0.29, p = 0.003). In total, significant sex * SNP
      interactions were found at 15 loci; pubertal stage * SNP interactions at 23 loci
      and 19 loci interacted with both sex and pubertal stage. In conclusion, variants
      originally associated with adult BMD influence bone mass in children of European
      ancestry, highlighting the fact that many of these loci operate early in life.
      However, the direction and magnitude of associations for a large number of SNPs
      only became evident when accounting for sex and maturation.

PMID- 25762185
TI  - Probing the adjustments of macromolecules during their surface adsorption.
AB  - Thiol-terminated polymers poly(2-methacryloyloxyethyl phosphorylcholine) (PMPC
      SH), poly(N,N-isopropylacrylamide) (PNIPAM-SH), and poly(tert-butyl acrylate)
      (PtBA-SH) were synthesized, and the polymers were grafted on the gold surfaces of
      quartz crystal microbalance with dissipation (QCM-D) and surface plasmon
      resonance (SPR) sensor chips to form brushes. The grafting process of the polymer
      brushes as well as protein adsorption onto the brush layers was monitored by in
      situ QCM-D and SPR techniques. By examining the changes in frequency and
      dissipation factor as well as the value of ?D/?f from QCM-D measurements,
      different stages of the polymer grafting and protein adsorption are
      distinguished. The most interesting discovery is the conformation change of BSA
      protein adsorption from a weakly adsorbed native state to a strongly immobilized
      denatured state on the polymer brushes. The corresponding change in BSA
      adsorption from a reversible state to an irreversible state was confirmed by SPR
      measurements. The adsorption of protein on the polymer brushes' surface relies
      largely on interaction between the protein and the polymers, and the stronger
      hydrophilicity of the surfaces is proved to be more effective to suppress the
      protein adsorption. Analysis of the D-f plot of QCM-D measurements helps to
      characterize different binding strength of protein and the underlying polymer
      surface. 

PMID- 25762184
TI  - Association of TNF-alpha with impaired migration capacity of mesenchymal stem
      cells in patients with systemic lupus erythematosus.
AB  - Previous studies indicated that bone marrow mesenchymal stem cells (BMSCs) from
      patients with systemic lupus erythematosus (SLE) exhibited impaired capacities of
      proliferation, differentiation, and immune modulation. Considering that migration
      capacity is important for the exertion of BMSCs functions, the defects in
      migration might contribute to BMSCs dysfunction in SLE patients. In this study,
      we showed that the migration capacity of SLE BMSCs was remarkably impaired in
      comparison with those of healthy controls. Increased tumor necrosis factor alpha
      (TNF-alpha) in SLE serum significantly inhibited the migration capacity and in
      vivo homing capacity of SLE BMSCs via a specific TNF receptor I (TNFRI) manner,
      in which decreased HGF mRNA production caused by the activation of I kappa B
      kinase beta (IKK-beta) pathway is partially involved. To our knowledge, this is
      the first report to discuss the possible mechanisms for impaired migration of
      BMSCs in SLE patients. Our results suggest that inhibition of TNF-alpha pathway
      might be helpful for accelerating BMSCs migration to the inflammatory
      microenvironment in SLE patients, thereby having a potential role in SLE
      treatment. 

PMID- 25762187
TI  - Morphological and molecular characterization of Eurytrema cladorchis parasitizing
      cattle (Bos indicus) in Bangladesh.
AB  - There is always controversy regarding identification of different species in the
      genus Eurytrema. Identification has been based mainly on morphology, which can be
      misleading and subject to differing interpretation among the scientists.
      Therefore, the aim of this study was to identify Eurytrema flukes both by
      morphology and molecular properties on the basis of 18-subunit ribosomal RNA (18S
      rRNA) gene as well as internal transcribed spacer 2 (ITS2) to clarify their
      phylogenetic status. Among six different agroecological areas of Bangladesh, 22
      Eurytrema flukes were recovered from the bile ducts of 22 cattle in Bandarban, a
      hill district. The flukes were identified as Eurytrema cladorchis through
      morphometric and morphological studies. Phylogenetic analyses were conducted by
      neighbor-joining phylogram inferred from both 18S rRNA (1784 bp) gene and ITS2
      (229 bp) sequences. A monophyletic clade was constructed by the E. cladorchis
      from Bangladesh; however, the clade was distinct from those formed by Eurytrema
      pancreaticum and Eurytrema coelomaticum. This study first described the existence
      of E. cladorchis from Bangladesh and may provide useful information for both
      morphological and molecular properties that may further help to clarify
      phylogenetic relationships within the genus Eurytrema and also for other
      digeneans.

PMID- 25762186
TI  - Magnetic resonance imaging with superparamagnetic iron oxide fails to track the
      long-term fate of mesenchymal stem cells transplanted into heart.
AB  - MRI for in vivo stem cell tracking remains controversial. Here we tested the
      hypothesis that MRI can track the long-term fate of the superparamagnetic iron
      oxide (SPIO) nanoparticles labelled mesenchymal stem cells (MSCs) following
      intramyocardially injection in AMI rats. MSCs (1 * 10(6)) from male rats doubly
      labeled with SPIO and DAPI were injected 2 weeks after myocardial infarction. The
      control group received cell-free media injection. In vivo serial MRI was
      performed at 24 hours before cell delivery (baseline), 3 days, 1, 2, and 4 weeks
      after cell delivery, respectively. Serial follow-up MRI demonstrated large
      persistent intramyocardial signal-voids representing SPIO during the follow-up of
      4 weeks, and MSCs did not moderate the left ventricular dysfunction. The TUNEL
      analysis confirmed that MSCs engrafted underwent apoptosis. The histopathological
      studies revealed that the site of cell injection was infiltrated by inflammatory
      cells progressively and the iron-positive cells were macrophages identified by
      CD68 staining, but very few or no DAPI-positive stem cells at 4 weeks after cells
      transplantation. The presence of engrafted cells was confirmed by real-time PCR,
      which showed that the amount of Y-chromosome-specific SRY gene was consistent
      with the results. MRI may not reliably track the long-term fate of SPIO-labeled
      MSCs engraftment in heart. 

PMID- 25762188
TI  - Hymenolepis folkertsi n. sp. (Eucestoda: Hymenolepididae) in the oldfield mouse
      Peromyscus polionotus (Wagner) (Rodentia: Cricetidae: Neotominae) from the
      southeastern Nearctic with comments on tapeworm faunal diversity among deer mice.
AB  - A previously unrecognized species of hymenolepidid cestode attributable to
      Hymenolepis is described based on specimens in Peromyscus polionotus, oldfield
      mouse, from Georgia near the southeastern coast of continental North America.
      Specimens of Hymenolepis folkertsi n. sp. differ from those attributed to most
      other species in the genus by having testes arranged in a triangle and a scolex
      with a prominent rostrum-like protrusion. The newly recognized species is further
      distinguished by the relative position and length of the cirrus sac, shape of
      seminal receptacle, and relative size of external seminal vesicle and seminal
      receptacle. Hymenolepidid cestodes have sporadically been reported among the
      highly diverse assemblage of Peromyscus which includes 56 distinct species in the
      Nearctic. Although the host genus has a great temporal duration and is endemic to
      the Nearctic, current evidence suggests that tapeworm faunal diversity reflects
      relatively recent assembly through bouts of host switching among other cricetid,
      murid, and geomyid rodents in sympatry. 

PMID- 25762189
TI  - Enteric protozoa of cats and their zoonotic potential-a field study from Austria.
AB  - Domestic cats can be infected with a variety of enteric protozoa. Genotyping of
      protozoan species, especially Giardia as the most common, can improve assessment
      of their relevance as zoonotic agents. For an overview on the occurrence of
      feline enteric protozoa, 298 faecal samples of cats from private households,
      catteries and animal shelters in Austria were collected. All samples were
      examined by flotation and using a rapid test for Giardia (FASTest). For the
      detection of Tritrichomonas blagburni, freshly voided faeces (n = 40) were
      processed using a commercial culturing system (InPouch TF-Feline). Genotyping was
      done at the beta-giardin gene loci (each sample) and triosephosphate isomerase
      gene loci (positive samples) for Giardia and at the 18S rRNA gene (positive
      samples) for Cryptosporidium. Thirty-seven samples (12.4%) were positive for
      Giardia by flotation and/or using a rapid test. Cryptosporidium was present in
      1.7%, Cystoisospora in 4.0%, Sarcocystis in 0.3% and T. blagburni in 2.5% of the
      samples. Genotyping revealed Giardia cati, the potentially zoonotic Giardia
      duodenalis and Cryptosporidium felis. Most of the infected cats had no diarrhoea.
      Cats from shelters were significantly more often infected than owned cats (p =
      0.01). When comparing Giardia detection methods, the rapid test had a higher
      sensitivity than flotation. Polymerase chain reaction (PCR) results were mostly
      independent from the other two tests.

PMID- 25762190
TI  - Linear intraoperative ultrasound probes and phased-array probes: two sides of the
      same coin.

PMID- 25762191
TI  - Preparation, characterization, and antibacterial activity of silver nanoparticle
      decorated graphene oxide nanocomposite.
AB  - In this work, we report a facile and green approach to prepare a uniform silver
      nanoparticles (AgNPs) decorated graphene oxide (GO) nanocomposite (GO-Ag). The
      nanocomposite was fully characterized by transmission electron microscopy (TEM),
      Fourier transform infrared (FTIR) spectra, ultraviolet-visible (UV-vis)
      absorption spectra, and X-ray photoelectron spectroscopy (XPS), which
      demonstrated that AgNPs with a diameter of approximately 22 nm were uniformly and
      compactly deposited on GO. To investigate the silver ion release behaviors, HEPES
      buffers with different pH (5.5, 7, and 8.5) were selected and the mechanism of
      release actions was discussed in detail. The cytotoxicity of GO-Ag nanocomposite
      was also studied using HEK 293 cells. GO-Ag nanocomposite displayed good
      cytocompatibility. Furthermore, the antibacterial properties of GO-Ag
      nanocomposite were studied using Gram-negative E. coli ATCC 25922 and Gram
      positive S. aureus ATCC 6538 by both the plate count method and disk diffusion
      method. The nanocomposite showed excellent antibacterial activity. These results
      demonstrated that GO-Ag nanocomposite, as a kind of antibacterial material, had a
      great promise for application in a wide range of biomedical applications. 

PMID- 25762192
TI  - Synthesis and evaluation of optical and PET GLP-1 peptide analogues for GLP-1R
      imaging.
AB  - A fluorescein-GLP-1 (7-37) analog was generated to determine GLP-1R distribution
      in various cell types of the pancreas in both strains of mice and receptor
      specific uptake was confirmed by blocking with exendin-4. Biodistribution studies
      were carried out using 68Ga-labeled GLP-1(7-37) peptides in CD1 and C57BL/6 mice.
      In addition, immunocompromised mice bearing GLP-1R-expressing insulinomas were
      evaluated by positron emission tomography (PET) imaging and ex vivo
      biodistribution studies. The optical GLP-1 probe strongly colocalized with
      immunofluorescence for insulin and glucagon, and more weakly with amylase
      (exocrine pancreas) and cytokeratin 19 (ductal cells), confirming its application
      for in situ GLP-1R imaging in various pancreatic cell types. Insulinomas were
      clearly visualized by in vivo PET. Reducing the peptide positive charge decreased
      renal retention as well as tumor uptake. Results demonstrate the application of
      the developed GLP-1 peptide analogues for in situ (optical) and in vivo (PET)
      imaging of GLP-1R expression.

PMID- 25762193
TI  - Strategies to inhibit alloantibody production in alloprimed murine recipients of
      hematopoietic stem cell grafts.
AB  - Alloantibody, not primed T cells, is the major barrier to bone marrow (BM)
      engraftment in allosensitized mice. We have shown that a single intravenous
      injection of donor splenocytes, to mimic a blood transfusion, results in high,
      sustained levels of serum alloantibody sufficient to eliminate donor BM within 3
      h, resulting in uniform mortality in lethally irradiated allogeneic recipients.
      Current studies focused preventing and treating allopriming. Blockade of B cell
      survival signals with mTACI-Ig pre- and postpriming was ineffective, as was the B
      cell but not plasma cell depleting anti-CD20 mAb. Germinal center formation
      inhibition by lymphotoxin-beta receptor-Ig (LbetaR-Ig) diminished
      allosensitization, although conditional Prmd1 (Blimp-1) deletion in CD19+ cells
      was highly effective. By combining anti-CD20 mAb to reduce B cells and LTbetaR-Ig
      to diminish the frequency of B cells that could form germinal centers pre- and
      postpriming, allosensitization was precluded, permitting long-term survival in T-
      and NK-depleted, irradiated allogeneic recipients, whereas combined therapy
      postpriming alone was ineffective. As evidence of the critical role of B cells,
      the proteosomal inhibitor, bortezomib, given unencapsulated or encapsulated,
      proved ineffective in influencing allosensitization. These data extend our
      understanding of allopriming and provide a potential therapy for patients at risk
      for allosensitization and BM graft rejection. 

PMID- 25762194
TI  - Trends in the epidemiology of invasive Haemophilus influenzae disease in
      Queensland, Australia from 2000 to 2013: what is the impact of an increase in
      invasive non-typable H. influenzae (NTHi)?
AB  - Following the introduction of vaccination against Haemophilus influenzae type b
      (Hib), cases of invasive encapsulated Hib disease have decreased markedly. This
      study aimed to examine subsequent epidemiological trends in invasive H.
      influenzae disease in Queensland, Australia and in particular, assess the
      clinical impact and public health implications of invasive non-typable H.
      influenzae (NTHi) strains. A multicentre retrospective study was conducted from
      July 2000 to June 2013. Databases of major laboratories in Queensland including
      Queensland Forensic and Scientific Services (jurisdictional referral laboratory
      for isolate typing) were examined to identify cases. Demographic, infection site,
      Indigenous status, serotype, and mortality data were collected. In total, 737
      invasive isolates were identified, of which 586 (79.5%) were serotyped. Hib, NTHi
      and encapsulated non-b strains, respectively, constituted 12.1%, 69.1% and 18.8%
      of isolates. The predominant encapsulated non-b strains were f (45.5%) and a
      (27.3%) serotypes. Of isolates causing meningitis, 48.9% were NTHi, 14.9% Hib,
      14.9% Hie, 10.6% Hif, 6.4% Hia and 4.3% were untyped. During the study period,
      there was an increase in the incidence of invasive NTHi disease (P = 0.007) with
      seasonal peaks in winter and spring (P 0.001) and Hib (P = 0.039) than non
      Indigenous patients. In Queensland, invasive H. influenzae disease is now
      predominantly encountered in adults and most commonly caused by NTHi strains with
      demonstrated pathogenicity extending to otherwise young or immunocompetent
      individuals. Routine public health notification of these strains is recommended
      and recent available immunization options should be considered. 

PMID- 25762195
TI  - Laplacian spectra of a class of small-world networks and their applications.
AB  - One of the most crucial domains of interdisciplinary research is the relationship
      between the dynamics and structural characteristics. In this paper, we introduce
      a family of small-world networks, parameterized through a variable d controlling
      the scale of graph completeness or of network clustering. We study the Laplacian
      eigenvalues of these networks, which are determined through analytic recursive
      equations. This allows us to analyze the spectra in depth and to determine the
      corresponding spectral dimension. Based on these results, we consider the
      networks in the framework of generalized Gaussian structures, whose physical
      behavior is exemplified on the relaxation dynamics and on the fluorescence
      depolarization under quasiresonant energy transfer. Although the networks have
      the same number of nodes (beads) and edges (springs) as the dual Sierpinski
      gaskets, they display rather different dynamic behavior. 

PMID- 25762196
TI  - Increased levels of irisin in people with long-standing Type 1 diabetes.
AB  - BACKGROUND: Irisin stimulates browning of white adipose tissue and improves
      metabolic control in mice. Betatrophin, another recently described hormone,
      improves metabolic control in mice by inducing beta-cell proliferation. In vitro,
      irisin stimulates the expression of betatrophin in rat adipocytes. There is a
      great interest in developing drugs that target or use these hormones for the
      treatment of obesity and diabetes. We have previously reported on increased
      levels of betatrophin in people with Type 1 diabetes, but the levels of irisin
      are currently unknown. AIM: To characterize the levels of irisin in Type 1
      diabetes and investigate a potential correlation with betatrophin. METHODS:
      Irisin and betatrophin were measured by enzyme-linked immunosorbant assay (ELISA)
      in 45 individuals with Type 1 diabetes and in 25 healthy controls. RESULTS:
      Irisin levels were increased in people with Type 1 diabetes, and especially in
      women. Negative correlations between irisin levels and age at onset of Type 1
      diabetes and plasma triacylglycerol levels were observed. Interestingly, in women
      with Type 1 diabetes a negative correlation between irisin and insulin doses was
      also observed. When computing correlations for all study participants, a positive
      correlation between irisin and total betatrophin was observed, but not between
      irisin and full-length betatrophin. CONCLUSION: We report on increased
      circulating levels of irisin in people with Type 1 diabetes, especially in women.
      For women with Type 1 diabetes, the levels of irisin correlated with lower
      insulin requirements. Further studies are clearly needed to determine the role of
      irisin in Type 1 diabetes.

PMID- 25762197
TI  - Effect of Exercise Training and L-arginine on Oxidative Stress and Left
      Ventricular Function in the Post-ischemic Failing Rat Heart.
AB  - The aim of the present study was to evaluate the effect of exercise training (ET)
      and L-arginine on oxidative stress and ventricular function in rat with
      myocardial infarction (MI). Four weeks after the surgical procedures, 40 Wistar
      male rats were randomized to the following groups: MI-sedentary (Sed); MI
      exercise (Ex); MI-sedentary + L-arginine (Sed + LA); and MI-exercise + L-arginine
      (Ex + LA); the rats were subjected to aerobic training in the form of treadmill
      running. Rats in the L-arginine-treated groups drank water containing 4 % L
      arginine. Before and after the training program, all subjects underwent resting
      echocardiography. Catalase (CAT) glutathione peroxidase (GPx), malondialdehyde
      (MDA) and myeloperoxidase (MPO) were measured. Cardiac output, stroke volume and
      fractional shortening in Ex and Ex + LA groups significantly increased in
      comparison with the Sed group. Cardiac systolic function indices in Ex + LA group
      were significantly greater than Ex group. Also, GPx activity and MDA,
      respectively, increased and decreased in response to ET, but no change was
      observed in MPO and CAT. These results suggest that ET increased LV function by
      decreasing oxidative stress and increasing antioxidant defense system in rats
      with MI. In addition in response to training, L-arginine appears to have additive
      effect on cardiac function, but have no effect on oxidative stress indices. 

PMID- 25762198
TI  - Bayesian path specific frailty models for multi-state survival data with
      applications.
AB  - Multi-state models can be viewed as generalizations of both the standard and
      competing risks models for survival data. Models for multi-state data have been
      the theme of many recent published works. Motivated by bone marrow transplant
      data, we propose a Bayesian model using the gap times between two successive
      events in a path of events experienced by a subject. Path specific frailties are
      introduced to capture the dependence structure of the gap times in the paths with
      two or more states. Under improper prior distributions for the parameters, we
      establish propriety of the posterior distribution. An efficient Gibbs sampling
      algorithm is developed for drawing samples from the posterior distribution. An
      extensive simulation study is carried out to examine the empirical performance of
      the proposed approach. A bone marrow transplant data set is analyzed in detail to
      further demonstrate the proposed methodology. 

PMID- 25762199
TI  - A new low-voltage plateau of Na3V2(PO4)3 as an anode for Na-ion batteries.
AB  - A low-voltage plateau at ~0.3 V is discovered for the deep sodiation of
      Na3V2(PO4)3 by combined computational and experimental studies. This new low
      voltage plateau doubles the sodiation capacity of Na3V2(PO4)3, thus turning it
      into a promising anode for Na-ion batteries. 

PMID- 25762201
TI  - Non-invasive prediction of intra-amniotic infection and/or inflammation in
      patients with cervical insufficiency or an asymptomatic short cervix (<=15 mm).
AB  - PURPOSE: To identify non-invasive parameters to predict intra-amniotic infection
      and/or inflammation (IAI) in patients with cervical insufficiency or an
      asymptomatic short cervix (<=15 mm). METHODS: This retrospective cohort study
      included 72 asymptomatic women with cervical insufficiency (n = 54) or an
      asymptomatic short cervix (n = 18) at 17-28 weeks. Maternal blood was collected
      for the determination of the C-reactive protein (CRP) level and white blood cell
      (WBC) count, and sonography was performed to measure the cervical length shortly
      after amniocentesis. Amniotic fluid (AF) was cultured and interleukin-6 (IL-6)
      level and WBC count were determined. RESULTS: The prevalence of intra-amniotic
      inflammation and a positive AF culture was 22.2 % (16/72) and 8.3 % (6/72),
      respectively. The best cut-off value for AF IL-6 in predicting the presence of
      intra-amniotic infection was >=7.6 ng/mL and was used to diagnose the presence of
      intra-amniotic inflammation. Women with intra-amniotic inflammation, regardless
      of culture results, were at increased risk for preterm delivery and adverse
      outcomes compared to women without intra-amniotic inflammation. In multivariable
      regression, CRP was the only non-invasive variable statistically significantly
      associated with IAI. Moreover, the area under the curves for the CRP and AF WBC
      were not significantly different. CONCLUSIONS: In women with cervical
      insufficiency or a short cervix, the risk for IAI can be predicted fairly and non
      invasively by measurements of serum CRP. Overall, this non-invasive parameter
      appears to have similar accuracy to the AF WBC counts for predicting IAI.

PMID- 25762202
TI  - The criteria to suspect chronic myeloid leukemia using absolute basophil counts
      in peripheral blood.

PMID- 25762203
TI  - Dual-modality probe intended for prostate cancer detection combining Raman
      spectroscopy and tactile resonance technology--discrimination of normal human
      prostate tissues ex vivo.
AB  - Prostate cancer is the most common cancer for men in the western world. For the
      first time, a dual-modality probe, combining Raman spectroscopy and tactile
      resonance technology, has been used for assessment of fresh human prostate
      tissue. The study investigates the potential of the dual-modality probe by
      testing its ability to differentiate prostate tissue types ex vivo. Measurements
      on four prostates show that the tactile resonance modality was able to
      discriminate soft epithelial tissue and stiff stroma (p < 0.05). The Raman
      spectra exhibited a strong fluorescent background at the current experimental
      settings. However, stroma could be discerned from epithelia by integrating the
      value of the spectral background. Combining both parameters by a stepwise
      analysis resulted in 100% sensitivity and 91% specificity. Although no cancer
      tissue was analysed, the results are promising for further development of the
      instrument and method for discriminating prostate tissues and cancer. 

PMID- 25762200
TI  - Vimentin regulates activation of the NLRP3 inflammasome.
AB  - Activation of the NLRP3 inflammasome and subsequent maturation of IL-1beta have
      been implicated in acute lung injury (ALI), resulting in inflammation and
      fibrosis. We investigated the role of vimentin, a type III intermediate filament,
      in this process using three well-characterized murine models of ALI known to
      require NLRP3 inflammasome activation. We demonstrate that central
      pathophysiologic events in ALI (inflammation, IL-1beta levels, endothelial and
      alveolar epithelial barrier permeability, remodelling and fibrosis) are
      attenuated in the lungs of Vim(-/-) mice challenged with LPS, bleomycin and
      asbestos. Bone marrow chimeric mice lacking vimentin have reduced IL-1beta levels
      and attenuated lung injury and fibrosis following bleomycin exposure.
      Furthermore, decreased active caspase-1 and IL-1beta levels are observed in vitro
      in Vim(-/-) and vimentin-knockdown macrophages. Importantly, we show direct
      protein-protein interaction between NLRP3 and vimentin. This study provides
      insights into lung inflammation and fibrosis and suggests that vimentin may be a
      key regulator of the NLRP3 inflammasome. 

PMID- 25762204
TI  - Syntaxin-4 mediates exocytosis of pre-docked and newcomer insulin granules
      underlying biphasic glucose-stimulated insulin secretion in human pancreatic beta
      cells.
AB  - AIMS/HYPOTHESIS: Of the four exocytotic syntaxins (Syns), much is now known about
      the role of Syn-1A (pre-docked secretory granules [SGs]) and Syn-3 (newcomer SGs)
      in insulin exocytosis. Some work was reported on Syn-4's role in biphasic glucose
      stimulated insulin secretion (GSIS), but its precise role in insulin SG
      exocytosis remains unclear. In this paper we examine this role in human beta
      cells. METHODS: Endogenous function of Syn-4 in human islets was assessed by
      knocking down its expression with lentiviral single hairpin RNA (lenti-shRNA)
      RFP. Biphasic GSIS was determined by islet perifusion assay. Single-cell analysis
      of exocytosis of red fluorescent protein (RFP)-positive beta cells (exhibiting
      near-total depletion of Syn-4) was by patch clamp capacitance measurements (Cm)
      and total internal reflection fluorescence microscopy (TIRFM), the latter to
      further assess single SG behaviour. Co-immunoprecipitations were conducted on INS
      1 cells to assess exocytotic complexes. RESULTS: Syn-4 knockdown (KD) of 77% in
      human islets caused a concomitant reduction in cognate Munc18c expression (46%)
      without affecting expression of other exocytotic proteins; this resulted in
      reduction of GSIS in the first phase (by 42%) and the second phase (by 40%). Cm
      of RFP-tagged Syn-4-KD beta cells showed severe inhibition in the readily
      releasable pool (by 71%) and mobilisation from reserve pools (by 63%). TIRFM
      showed that Syn-4-KD-induced inhibition of first-phase GSIS was attributed to
      reduction in exocytosis of both pre-docked and newcomer SGs (which undergo
      minimal residence or docking time at the plasma membrane before fusion). Second
      phase inhibition was attributed to reduction in newcomer SGs. Stx-4 co
      immunoprecipitated Munc18c, VAMP2 and VAMP8, suggesting that these exocytotic
      complexes may be involved in exocytosis of pre-docked and newcomer SGs.
      CONCLUSIONS/INTERPRETATION: Syn-4 is involved in distinct molecular machineries
      that influence exocytosis of both pre-docked and newcomer SGs in a manner
      functionally redundant to Syn-1A and Syn-3, respectively; this underlies Syn-4's
      role in mediating portions of first-phase and second-phase GSIS.

PMID- 25762206
TI  - Parent and family factors associated with service use by young people with mental
      health problems: a systematic review.
AB  - AIM: To conduct a systematic review of parent and family factors associated with
      service use for young people with mental health problems, to inform early
      intervention efforts aimed at increasing service use by young people. METHODS: A
      systematic search of academic databases was performed. Articles were included in
      the review if they had: a sample of young people aged between 5 and 18 years;
      service use as the outcome measure; one or more parental or family variables as a
      predictor; and a comparison group of non-service using young people with mental
      health problems. In order to focus on factors additional to need, the mental
      health symptoms of the young person also had to be controlled for. Stouffer's
      method of combining P-values was used to draw conclusions as to whether or not
      associations between variables were reliable. RESULTS: Twenty-eight articles were
      identified investigating 15 parental or family factors, 7 of which were found to
      be associated with service use for a young person with mental health needs:
      parental burden, parent problem perception, parent perception of need, parent
      psychopathology, single-parent household, change in family structure and being
      from the dominant ethnic group for the United States specifically. Factors not
      found to be related to service use were: family history of service use, parent
      child relationship quality, family functioning, number of children, parent
      education level, parent employment status, household income and non-urban
      location of residence. CONCLUSIONS: A number of family-related factors were
      identified that can inform effective interventions aimed at early intervention
      for mental health problems. Areas requiring further research were also
      identified.

PMID- 25762205
TI  - Delayed timing of post-challenge peak blood glucose predicts declining beta cell
      function and worsening glucose tolerance over time: insight from the first year
      postpartum.
AB  - AIMS/HYPOTHESIS: On cross-sectional assessment, a delayed timing of the peak
      blood glucose level at >=60 min post-challenge on an OGTT is associated with beta
      cell dysfunction. In this context, we hypothesised that longitudinal changes in
      the timing of this peak might predict changes in glucose metabolism. We thus
      sought to evaluate the longitudinal associations of changes in the timing of the
      peak glucose level with changes over time in insulin sensitivity, beta cell
      function and glucose tolerance. METHODS: A total of 532 women underwent an OGTT
      at both 3 months and 12 months postpartum. The participants were stratified into
      four groups according to the change in timing of their glucose peak between the
      two visits: women with no change in timing of the glucose peak at 30 min (n =
      217), those whose glucose peak shifted to an earlier time point (n = 120), those
      whose peak shifted to a later time point (n = 87) and women with an unchanged
      glucose peak at >=60 min (n = 108). Beta cell function was measured using the
      Insulin Secretion-Sensitivity Index-2 (ISSI-2). RESULTS: Compared with an
      unchanged glucose peak at 30 min, both the shift of the glucose peak to a later
      time point and a peak that was unchanged at >=60 min were independently
      associated with declining ISSI-2 scores (beta = -127.5, p < 0.001 and beta = 
      98.8, p = 0.006, respectively) and increased 2 h post-challenge glucose levels
      (beta = 1.28, p < 0.001 and beta = 0.91, p < 0.001, respectively) between the two
      visits. Furthermore, both these patterns of change in peak were independently
      associated with worsening glucose tolerance (from normal to prediabetes [defined
      as impaired fasting glucose or impaired glucose tolerance]/diabetes or from
      prediabetes to diabetes) (OR 8.1, 95% CI 3.0, 22.1 and OR 3.7, 95% CI 1.2, 11.7,
      respectively). CONCLUSIONS/INTERPRETATION: A delayed timing of the post-challenge
      peak glucose level is associated with declining beta cell function and worsening
      glucose tolerance over time.

PMID- 25762207
TI  - The Effect of Medicare Eligibility on Spousal Insurance Coverage.
AB  - A majority of married couples in the USA take advantage of the fact that
      employers often provide health insurance coverage to spouses. When older spouses
      become eligible for Medicare, however, many of them can no longer provide their
      younger spouses with coverage. In this paper, we study how spousal eligibility
      for Medicare affects the health insurance and health care access of younger
      spouses. We find that spousal eligibility for Medicare results in younger spouses
      no longer having employers pay for their insurance and being less likely to have
      employer-sponsored coverage. Instead, younger spouses switch to privately
      purchased coverage, which tends to be worse than what they had before their
      spouses became eligible for Medicare. We also find suggestive evidence that
      younger spouses are less likely to use health care services after their older
      spouses become eligible for Medicare.

PMID- 25762208
TI  - A benzotriazole-mediated route to protected marine-derived hetero-2,5
      diketopiperazines containing proline.
AB  - A procedure for the cyclization of dipeptidoyl benzotriazolides containing
      proline derivatives promoted by triethylamine under MW activation is introduced.
      The reaction is general for a variety of dipeptidoyl benzotriazolides and
      represents a very practical and convenient method for the preparation of Pro- or
      Hyp-derived 2,5-diketopiperazines (2,5-DKPs) and bis-DKPs with a disulfide
      linker. This method can be used for the construction of 2,5-DKP compound
      libraries and for the synthesis of natural products with diketopiperazine cores. 

PMID- 25762210
TI  - Genetics of anxiety disorders: Genetic epidemiological and molecular studies in
      humans.
AB  - This review provides a broad overview of the state of research in the genetics of
      anxiety disorders (AD). Genetic epidemiological studies report a moderate level
      of familial aggregation (odds ratio: 4-6) and heritability estimates are about 30
      50%. Twin studies suggest that the genetic architecture of AD is not isomorphic
      with their classifications, sharing risk factors with each other. So far, linkage
      and association studies of AD have produced inconclusive results. Genome-wide
      association studies of AD can provide an unbiased survey of common genetic
      variations across the entire genome. Given the shared causes of AD that transcend
      our current diagnostic classifications, clustering anxiety phenotypes into
      broader groups may be a powerful approach to identifying susceptibility locus for
      AD. Using such a shared genetic risk factor, meta-analyses of genome-wide
      association studies of AD conducted by large consortia are needed. Environmental
      factors also make a substantial contribution to the cause of AD. Although
      candidate gene studies of gene by environmental (G * E) interaction have appeared
      recently, no genome-wide search for G * E interactions have been performed.
      Epigenetic modification of DNA appears to have important effects on gene
      expression mediating environmental influences on disease risk. Given that G * E
      can be linked to an epigenetic modification, a combination analysis of genome
      wide G * E interaction and methylation could be an alternative method to find
      risk variants for AD. This genetic research will enable us to utilize more
      effective strategies for the prevention and treatment of AD in the near future.

PMID- 25762209
TI  - Gene therapy of inherited retinal degenerations: prospects and challenges.
AB  - Because of its favorable anatomical and immunological characteristics, the eye
      has been at the forefront of translational gene therapy. Dozens of promising
      proofs of concept have been obtained in animal models of inherited retinal
      degenerations (IRDs), and some of them have been relayed to the clinic. The
      results from the first clinical trials for a congenital form of blindness have
      generated great interest and have demonstrated the safety and efficacy of
      intraocular administrations of viral vectors in humans. However, this progress
      has also generated new questions and posed challenges that need to be addressed
      to further expand the applicability of gene therapy in the eye, including safe
      delivery of viral vectors to the outer retina, treatment of dominant IRDs as well
      as of IRDs caused by mutations in large genes, and, finally, selection of the
      appropriate IRDs and patients to maximize the efficacy of gene transfer. This
      review summarizes the strategies that are currently being exploited to overcome
      these challenges and drive the clinical development of retinal gene therapy. 

PMID- 25762212
TI  - High-sensitivity cardiac troponin I in the clinical setting: a rapidly developing
      field.

PMID- 25762211
TI  - Kidney injury molecule-1 and neutrophil gelatinase-associated lipocalin as
      prognostic markers in idiopathic membranous nephropathy.
AB  - BACKGROUND: Urinary excretion of alpha-1-microglobulin and beta-2-microglobulin
      reflects tubular damage and predicts outcome in patients with idiopathic
      membranous nephropathy with reasonable accuracy. Urinary kidney injury molecule-1
      and neutrophil gelatinase-associated lipocalin are novel biomarkers of tubular
      damage. We investigated if these markers could improve prediction of outcome in
      idiopathic membranous nephropathy. METHODS: We measured kidney injury molecule-1
      and neutrophil gelatinase-associated lipocalin in urine samples from patients
      with idiopathic membranous nephropathy, who had nephrotic proteinuria and normal
      renal function. Excretion of alpha-1-microglobulin and beta-2-microglobulin had
      been measured previously. Progression was defined as a serum creatinine rise
      >30%, a rise in serum creatinine to an absolute value of >=135 umol/L, or a
      clinical decision to start immunosuppressive therapy. Remission was defined as
      proteinuria <3.5 g/day and >50% reduction from baseline. RESULTS: Sixty-nine
      patients were included. Median follow-up was 35 months (interquartile range 18-63
      months). Progression occurred in 30 patients (44%), and spontaneous remission in
      36 (52%). Kidney injury molecule-1 and neutrophil gelatinase-associated lipocalin
      excretion rates were significantly correlated with each other, and with alpha-1
      microglobulin and beta-2-microglobulin. The areas under the receiver operating
      characteristic curves for progression were 0.75 (0.62-0.87) for kidney injury
      molecule-1 and 0.74 (0.62-0.87) for neutrophil gelatinase-associated lipocalin.
      In multivariate analysis with either alpha-1-microglobulin and beta-2
      microglobulin, kidney injury molecule-1 and neutrophil gelatinase-associated
      lipocalin did not independently predict outcome. CONCLUSION: Kidney injury
      molecule-1 and neutrophil gelatinase-associated lipocalin excretion rates
      correlated with excretion rates of other tubular damage markers and predicted
      outcome in patients with idiopathic membranous nephropathy. They did not add
      prognostic value compared to measurement of either alpha-1-microglobulin or beta
      2-microglobulin.

PMID- 25762213
TI  - Coronary artery spasm in the early phase of tako-tsubo cardiomyopathy: is this a
      primary cause of the disease?

PMID- 25762215
TI  - Interaction between visual and motor cortex: a transcranial magnetic stimulation
      study.
AB  - The major link between the visual and motor systems is via the dorsal stream
      pathways from visual to parietal and frontal areas of the cortex. Although the
      pathway appears to be indirect, there is evidence that visual input can reach the
      motor cortex at relatively short latency. To shed some light on its neural basis,
      we studied the visuomotor interaction using paired transcranial magnetic
      stimulation (TMS). Motor-evoked potentials (MEPs) were recorded from the right
      first dorsal interosseous in sixteen healthy volunteers. A conditioning stimulus
      (CS) was applied over the phosphene hotspot of the visual cortex, followed by a
      test stimulus over the left primary motor cortex (M1) with a random interstimulus
      interval (ISI) in range 12-40 ms. The effects of paired stimulation were retested
      during visual and auditory reaction-time tasks (RT). Finally, we measured the
      effects of a CS on short-interval intracortical inhibition (SICI). At rest, a CS
      over the occiput significantly (P < 0.001) suppressed test MEPs with an ISI in
      the range 18-40 ms. In the visual RT, inhibition with an ISI of 40 ms (but not 18
      ms) was replaced by a time-specific facilitation (P < 0.001), whereas, in the
      auditory RT, the CS no longer had any effect on MEPs. Finally, an occipital CS
      facilitated SICI with an ISI of 40 ms (P < 0.01). We conclude that it is possible
      to study separate functional connections from visual to motor cortices using
      paired-TMS with an ISI in the range 18-40 ms. The connections are inhibitory at
      rest and possibly mediated by inhibitory interneurones in the motor cortex. The
      effect with an ISI of 40 ms reverses into facilitation during a visuomotor RT but
      not an audiomotor RT. This suggests that it plays a role in visuomotor
      integration.

PMID- 25762214
TI  - Development of poly(ethylene glycol) hydrogels for salivary gland tissue
      engineering applications.
AB  - More than 40,000 patients are diagnosed with head and neck cancers annually in
      the United States with the vast majority receiving radiation therapy. Salivary
      glands are irreparably damaged by radiation therapy resulting in xerostomia,
      which severely affects patient quality of life. Cell-based therapies have shown
      some promise in mouse models of radiation-induced xerostomia, but they suffer
      from insufficient and inconsistent gland regeneration and accompanying secretory
      function. To aid in the development of regenerative therapies, poly(ethylene
      glycol) hydrogels were investigated for the encapsulation of primary
      submandibular gland (SMG) cells for tissue engineering applications. Different
      methods of hydrogel formation and cell preparation were examined to identify
      cytocompatible encapsulation conditions for SMG cells. Cell viability was much
      higher after thiol-ene polymerizations compared with conventional methacrylate
      polymerizations due to reduced membrane peroxidation and intracellular reactive
      oxygen species formation. In addition, the formation of multicellular
      microspheres before encapsulation maximized cell-cell contacts and increased
      viability of SMG cells over 14-day culture periods. Thiol-ene hydrogel
      encapsulated microspheres also promoted SMG proliferation. Lineage tracing was
      employed to determine the cellular composition of hydrogel-encapsulated
      microspheres using markers for acinar (Mist1) and duct (Keratin5) cells. Our
      findings indicate that both acinar and duct cell phenotypes are present
      throughout the 14 day culture period. However, the acinar:duct cell ratios are
      reduced over time, likely due to duct cell proliferation. Altogether, permissive
      encapsulation methods for primary SMG cells have been identified that promote
      cell viability, proliferation, and maintenance of differentiated salivary gland
      cell phenotypes, which allows for translation of this approach for salivary gland
      tissue engineering applications. 

PMID- 25762216
TI  - Motion immune diffusion imaging using augmented MUSE for high-resolution multi
      shot EPI.
AB  - PURPOSE: To develop new techniques for reducing the effects of microscopic and
      macroscopic patient motion in diffusion imaging acquired with high-resolution
      multishot echo-planar imaging. THEORY: The previously reported multiplexed
      sensitivity encoding (MUSE) algorithm is extended to account for macroscopic
      pixel misregistrations, as well as motion-induced phase errors in a technique
      called augmented MUSE (AMUSE). Furthermore, to obtain more accurate quantitative
      diffusion-tensor imaging measures in the presence of subject motion, we also
      account for the altered diffusion encoding among shots arising from macroscopic
      motion. METHODS: MUSE and AMUSE were evaluated on simulated and in vivo motion
      corrupted multishot diffusion data. Evaluations were made both on the resulting
      imaging quality and estimated diffusion tensor metrics. RESULTS: AMUSE was found
      to reduce image blurring resulting from macroscopic subject motion compared to
      MUSE but yielded inaccurate tensor estimations when neglecting the altered
      diffusion encoding. Including the altered diffusion encoding in AMUSE produced
      better estimations of diffusion tensors. CONCLUSION: The use of AMUSE allows for
      improved image quality and diffusion tensor accuracy in the presence of
      macroscopic subject motion during multishot diffusion imaging. These techniques
      should facilitate future high-resolution diffusion imaging.

PMID- 25762217
TI  - Natural yeast promoter variants reveal epistasis in the generation of
      transcriptional-mediated noise and its potential benefit in stressful conditions.
AB  - The increase in phenotypic variability through gene expression noise is proposed
      to be an evolutionary strategy in selective environments. Differences in promoter
      mediated noise between Saccharomyces cerevisiae strains could have been selected
      for thanks to the benefit conferred by gene expression heterogeneity in the
      stressful conditions, for instance, those experienced by industrial strains.
      Here, we used a genome-wide approach to identify promoters conferring high noise
      levels in the industrial wine strain EC1118. Many promoters of genes related to
      environmental factors were identified, some of them containing genetic variations
      compared with their counterpart in the laboratory strain S288c. Each variant of
      eight promoters has been fused to yeast-Enhanced Green Fluorescent Protein and
      integrated in the genome of both strains. Some industrial variants conferred
      higher expression associated, as expected, with lower noise, but other variants
      either increased or decreased expression without modifying variability, so that
      they might exhibit different levels of transcriptional-mediated noise at equal
      mean. At different induction conditions giving similar expression for both
      variants of the CUP1 promoter, we indeed observed higher noise with the
      industrial variant. Nevertheless, this difference was only observed in the
      industrial strain, revealing epistasis in the generation of promoter-mediated
      noise. Moreover, the increased expression variability conferred by this natural
      yeast promoter variant provided a clear benefit in the face of an environmental
      stress. Thus, modulation of gene expression noise by a combination of promoter
      modifications and trans-influences might be a possible adaptation mechanism in
      yeast. 

PMID- 25762218
TI  - Early history of high-altitude physiology.
AB  - High-altitude physiology can be said to have begun in 1644 when Torricelli
      described the first mercury barometer and wrote the immortal words "We live
      submerged at the bottom of an ocean of the element air." Interestingly, the
      notion of atmospheric pressure had eluded his teacher, the great Galileo. Blaise
      Pascal was responsible for describing the fall in pressure with increasing
      altitude, and Otto von Guericke gave a dramatic demonstration of the enormous
      force that could be developed by atmospheric pressure. Robert Boyle learned of
      Guericke's experiment and, with Robert Hooke, constructed the first air pump that
      allowed small animals to be exposed to a low pressure. Hooke also constructed a
      small low-pressure chamber and exposed himself to a simulated altitude of about
      2400 meters. With the advent of ballooning, humans were rapidly exposed to very
      low pressures, sometimes with tragic results. For example, the French balloon,
      Zenith, rose to over 8000 m, and two of the three aeronauts succumbed to the
      hypoxia. Paul Bert was the first person to clearly state that the deleterious
      effects of high altitude were caused by the low partial pressure of oxygen (PO2),
      and later research was accelerated by high-altitude stations and expeditions to
      high altitude. 

PMID- 25762219
TI  - Genetic variation influences the risk of bleeding after cardiac surgery: novel
      associations and validation of previous findings.
AB  - BACKGROUND: Severe post-operative bleeding in cardiac surgery is associated with
      increased morbidity and mortality. We hypothesized that variation in genetic
      susceptibility contributes to post-operative bleeding in addition to clinical
      factors. METHODS: We included 1036 adults undergoing cardiac surgery with
      cardiopulmonary bypass. Two different endpoints for excessive post-operative
      bleeding were used, either defined as blood loss exceeding 2 ml/kg/h the first 4
      h post-operatively or a composite including bleeding, transfusions, and
      reoperations. Twenty-two single nucleotide polymorphisms (SNPs) central in the
      coagulation and fibrinolysis systems or in platelet membrane receptors were
      genotyped, focusing on replication of earlier non-replicated findings and
      exploration of potential novel associations. Using logistic regression,
      significant SNPs were added to a model with only clinical variables to evaluate
      whether the genetic variables provided additional information. RESULTS:
      Univariate tests identified rs1799809 (located in the promoter region of the PROC
      gene), rs27646 and rs1062535 (in the ITGA2 gene), rs630014 (in the ABO gene), and
      rs6048 (in the F9 gene) as significantly associated with excessive post-operative
      bleeding (P < 0.05, P-values confirmed by permutation). The SNPs were significant
      also after adjustment with clinical variables, showing almost unchanged odds
      ratios except for rs1799809 (P = 0.06). Addition of the genetic covariates to a
      logistic regression model with clinical variables significantly improved the
      model (P < 0.01). CONCLUSION: We identified five SNPs associated with post
      operative bleeding after cardiac surgery, of which two validated previously
      published associations. Addition of genetic information to models with only
      clinical variables improved the models. Our results indicate that common genetic
      variations significantly influence post-operative bleeding after cardiac surgery.

PMID- 25762220
TI  - Expression of aquaporin 2 following facial nerve crush in rats.
AB  - CONCLUSION: We demonstrated an early increase in aquaporin 2 (AQP2) expression in
      a motor nerve (extratemporal facial nerve, FN) following acute peripheral
      compression (crush), concomitant to effective development of motor dysfunction
      (facial palsy). The early increase in AQP2 expression that occurred concomitantly
      with the appearance of a deficit in a peripheral motor nerve suggests that this
      protein is involved in the physiological events associated with post-injury
      edema, similar to the already demonstrated behavior of AQP4 in the central
      nervous system (CNS). OBJECTIVE: The aim of this study was to assess the
      expression of AQP2 in the FN of rats up to 7 days after crush. METHODS: The
      extratemporal trunk of the right FN of rats was subjected to mechanical crush,
      and the expression of AQP2 in the affected (right) and non-affected (left) FN was
      measured by means of western blotting at days 1, 3, and 7 after injury.
      Behavioral analysis of the development of facial palsy was also performed over
      the same time period. RESULTS: Increased expression of AQP2 was shown in the
      affected FN compared with its corresponding control at day 1 after compression,
      simultaneously with the appearance of facial palsy.

PMID- 25762221
TI  - Ebf2 is required for development of dopamine neurons in the midbrain
      periaqueductal gray matter of mouse.
AB  - Dopaminergic (DA) neurons in the midbrain ventral periaqueductal gray matter
      (PAG) play critical roles in various physiological and pathophysiological
      processes including sleep-wake rhyme, antinociception, and drug addiction.
      However, the molecular mechanisms underlying their development are poorly
      understood. Here, we showed that PAG DA neurons arose as early as E15.5 in mouse
      embryos. During the prenatal period, the majority of PAG DA neurons was
      distributed in the intermediate and caudal regions of the PAG. In the postnatal
      brain, ~50% of PAG DA neurons were preferentially located in the caudal portion
      of the PAG. Moreover, transcription factor early B-cell factor 2 (Ebf2) was
      transiently expressed in a subset of DA neurons in embryonic ventral
      mesencephalon. Functional analysis revealed that loss of Ebf2 in vivo caused a
      marked reduction in the number of DA neurons in the midbrain PAG but not in the
      substantia nigra and ventral tegmental area. Thus, Ebf2 is identified as a novel
      and important regulator selectively required for midbrain PAG DA neuron
      development.

PMID- 25762223
TI  - Interaction of ceruloplasmin with eosinophil peroxidase as compared to its
      interplay with myeloperoxidase: Reciprocal effect on enzymatic properties.
AB  - Myeloperoxidase (MPO) and eosinophil peroxidase (EPO) are involved in the
      development of halogenative stress during inflammation. We previously described a
      complex between MPO and ceruloplasmin (CP). Considering the high structural
      homology between MPO and EPO, we studied the latter's interaction with CP and
      checked whether EPO becomes inhibited in a complex with CP. Disc-electrophoresis
      and gel filtration showed that CP and EPO form a complex with the stoichiometry
      1:1. Affinity chromatography of EPO on CP-agarose (150 mM NaCl, 10 mM Na
      phosphate buffer, of pH 7.4) resulted in retention of EPO. EPO protects
      ceruloplasmin from limited proteolysis by plasmin. Only intact CP shifted the
      Soret band typical of EPO from 413 to 408 nm. The contact with CP likely causes
      changes in the heme pocket of EPO. Peroxidase activity of EPO with substrates
      such as guaiacol, orcinol, o-dianisidine, 4-chloro-1-naphtol, 3,3',5,5'
      tetramethylbenzidine, and 2,2'-azino-bis(3-ethylbenzthiazoline-6-sulfonate) is
      inhibited by CP in a dose-dependent manner. Similar to the interaction with MPO,
      the larger a substrate molecule, the stronger the inhibitory effect of CP upon
      EPO. The limited proteolysis of CP abrogates its capacity to inhibit the
      peroxidase activity of EPO. The peptide RPYLKVFNPR (corresponding to amino acids
      883-892 in CP) inhibits the peroxidase and chlorinating activity of EPO. Only the
      chlorinating activity of EPO is efficiently inhibited by CP, while the capacity
      of EPO to oxidize bromide and thiocyanate practically does not depend on the
      presence of CP. EPO enhances the p-phenylenediamine-oxidase activity of CP. The
      structural homology between the sites in the MPO and EPO molecules enabling them
      to contact CP is discussed. 

PMID- 25762222
TI  - Dawn- and dusk-phased circadian transcription rhythms coordinate anabolic and
      catabolic functions in Neurospora.
AB  - BACKGROUND: Circadian clocks control rhythmic expression of a large number of
      genes in coordination with the 24 hour day-night cycle. The mechanisms generating
      circadian rhythms, their amplitude and circadian phase are dependent on a
      transcriptional network of immense complexity. Moreover, the contribution of post
      transcriptional mechanisms in generating rhythms in RNA abundance is not known.
      RESULTS: Here, we analyzed the clock-controlled transcriptome of Neurospora
      crassa together with temporal profiles of elongating RNA polymerase II. Our data
      indicate that transcription contributes to the rhythmic expression of the vast
      majority of clock-controlled genes (ccgs) in Neurospora. The ccgs accumulate in
      two main clusters with peak transcription and expression levels either at dawn or
      dusk. Dawn-phased genes are predominantly involved in catabolic and dusk-phased
      genes in anabolic processes, indicating a clock-controlled temporal separation of
      the physiology of Neurospora. Genes whose expression is strongly dependent on the
      core circadian activator WCC fall mainly into the dawn-phased cluster while
      rhythmic genes regulated by the glucose-dependent repressor CSP1 fall
      predominantly into the dusk-phased cluster. Surprisingly, the number of rhythmic
      transcripts increases about twofold in the absence of CSP1, indicating that
      rhythmic expression of many genes is attenuated by the activity of CSP1.
      CONCLUSIONS: The data indicate that the vast majority of transcript rhythms in
      Neurospora are generated by dawn and dusk specific transcription. Our
      observations suggest a substantial plasticity of the circadian transcriptome with
      respect to the number of rhythmic genes as well as amplitude and phase of the
      expression rhythms and emphasize a major role of the circadian clock in the
      temporal organization of metabolism and physiology.

PMID- 25762224
TI  - Thyroid ultrasound findings in a follow-up survey of children from three Japanese
      prefectures: Aomori, Yamanashi, and Nagasaki.
AB  - We conducted ultrasound thyroid screening in cohort of 4,365 children aged
      between 3 to 18 years in three Japanese prefectures (Aomori, Yamanashi, and
      Nagasaki) using the same procedures as used in the Fukushima Health Survey. Forty
      four children had nodules >= 5.1 mm in diameter or cysts >= 20.1 mm in diameter
      detected at the first screening, and 31 of these children underwent the second
      follow-up survey. We collected information from thyroid ultrasound examinations
      and final clinical diagnoses and re-categorized the thyroid findings after the
      second examination. Twenty children had nodules >= 5.1 mm in diameter or cysts >=
      20.1 mm in diameter at the second examination; of these, one child was diagnosed
      with a thyroid papillary carcinoma and the remaining 19 children were diagnosed
      with possibly benign nodules such as adenomas, adenomatous nodules, and
      adenomatous goiters. A further 11 children were re-categorized as "no further
      examinations were required." Our results suggest that ultrasound thyroid findings
      in children may change with a relatively short-term passing period, and that
      thyroid cancer may exist at a very low but certain frequency in the general
      childhood population. 

PMID- 25762225
TI  - Effect of menstrual cycle on thermal perception and autonomic thermoregulatory
      responses during mild cold exposure.
AB  - We investigated the effects of menstrual cycle phase on thermal sensation,
      thermal pleasantness, and autonomic thermoregulatory responses during mild cold
      exposure. Eight healthy young women participated. Experiments were conducted in
      the follicular and luteal phases: 120 min exposure at 23.5  degrees C after 40
      min at a baseline temperature of 29  degrees C. Body core temperature was higher
      (P = 0.01) in the luteal phase than in the follicular phase. Thermal sensation of
      the whole body (P = 0.59), hands (P = 0.46), and toes (P = 0.94), and thermal
      pleasantness of the whole body (P = 0.79) were no different between phases. In
      both phases, mean skin temperature decreased (P = 0.00) in the same manner
      without any change in metabolic rate (P = 0.90). These results suggest the change
      of body core temperature in the menstrual cycle phases has no effect on thermal
      perception of cold or on autonomic cold-defense response.

PMID- 25762226
TI  - The effects of maintenance schedules following pulmonary rehabilitation in
      patients with chronic obstructive pulmonary disease: a randomised controlled
      trial.
AB  - OBJECTIVES: Pulmonary rehabilitation (PR) provides benefit for patients with
      chronic obstructive pulmonary disease (COPD) in terms of quality of life (QoL)
      and exercise capacity; however, the effects diminish over time. Our aim was to
      evaluate a maintenance programme for patients who had completed PR. SETTING:
      Primary and secondary care PR programmes in Norfolk. PARTICIPANTS: 148 patients
      with COPD who had completed at least 60% of a standard PR programme were
      randomised and data are available for 110 patients. Patients had greater than 20
      pack year smoking history and less than 80% predicted forced expiratory volume in
      1 s but no other significant disease or recent respiratory tract infection.
      INTERVENTIONS: Patients were randomised to receive a maintenance programme or
      standard care. The maintenance programme consisted of 2 h (1 h individually
      tailored exercise training and 1 h education programme) every 3 months for 1
      year. PRIMARY AND SECONDARY OUTCOME MEASURES: The Chronic Respiratory
      Questionnaire (CRQ) (primary outcome), endurance shuttle walk test (ESWT),
      EuroQol (EQ5D), hospital anxiety and depression score (HADS), body mass index
      (BMI), body fat, activity levels (overall score and activity diary) and
      exacerbations were assessed before and after 12 months. RESULTS: There was no
      statistically significant difference between the groups for the change in CRQ
      dyspnoea score (primary end point) at 12 months which amounted to 0.19 (-0.26 to
      0.64) units or other domains of the CRQ. There was no difference in the ESWT
      duration (-10.06 (-191.16 to 171.03) seconds), BMI, body fat, EQ5D, MET-minutes,
      activity rating, HADS, exacerbations or admissions. CONCLUSIONS: A maintenance
      programme of three monthly 2 h sessions does not improve outcomes in patients
      with COPD after 12 months. We do not recommend that our maintenance programme is
      adopted. Other methods of sustaining the benefits of PR are required. TRIAL
      REGISTRATION NUMBER: NCT00925171.

PMID- 25762227
TI  - Evidence-based development of a post-surgical lumbar discectomy leaflet
      intervention: a Delphi consensus study.
AB  - OBJECTIVE: To produce free, expert-informed postoperative information for lumbar
      discectomy patients, satisfying UK National Health Service Information Standards.
      DESIGN: A mixed methods approach utilising the Delphi technique and focus groups.
      SETTING: Five spinal centres across the UK. PARTICIPANTS: Panel members included
      23 physiotherapists, 11 patients and 17 spinal surgeons. INTERVENTION: Three
      rounds of questionnaires including open and closed questions and attendance at a
      clinician/patient focus group. RESULTS: Response rates of 85%, 26% and 35% were
      achieved for the Delphi rounds. Ten clinicians and six patients participated in
      the focus groups. Consensus for leaflet sections was achieved in round 1 and
      content in round 3. The focus groups informed further revisions. CONCLUSIONS: A
      consensually agreed, Information Standard compliant, patient lumbar discectomy
      leaflet was produced containing: (1) normal spine anatomy; (2) anatomy disc
      herniation and surgery; (3) back protection strategies and (4) frequently asked
      questions. Illustrations of exercises enable tailoring to the individual patient.

PMID- 25762228
TI  - Glycaemic control efficacy of oral antidiabetic drugs in treating type 2
      diabetes: a protocol for network meta-analysis.
AB  - INTRODUCTION: Past studies of network meta-analysis focused on evaluating drug
      combinations in treating type 2 diabetes but not on evaluating antidiabetic drugs
      in monotherapy. Clinical guidelines (eg, NICE (National Institute of Health and
      Care Excellence) clinical guidelines 66 and 87) were based only on the findings
      of individual clinical trials and pairwise meta-analysis in evaluating
      monotherapy. This study aims to fill this gap of research by conducting a
      Bayesian network meta-analysis to compare major antidiabetic drugs, including
      metformin, glimepiride, glyburide, glipizide, repaglinide, nateglinide,
      sitagliptin, vildagliptin, saxagliptin and SGLT-2 (sodium-glucose transporter-2)
      inhibitors. METHODS AND ANALYSES: Randomised controlled trials (RCTs) on the drug
      therapy of type 2 diabetes with outcome measures including glycosylated
      haemoglobin or fasting blood glucose will be included. The quality of included
      RTCs will be evaluated according to the Cochrane Collaboration's risk of bias
      tool. Traditional pairwise meta-analysis and Bayesian network meta-analysis will
      be conducted to compare the efficacies of antidiabetic drugs. Sensitivity
      analysis on the sample size of RCTs, meta-regression analysis on the follow-up
      periods, dosages and baselines of outcome measure, contradiction analysis between
      pairwise and network meta-analyses, and publication bias analysis, will be
      performed. ETHICS AND DISSEMINATION: Ethical approval is not required because
      this study includes no confidential personal data and interventions on the
      patients. Pairwise and network meta-analyses are based on the published RCT
      reports of eligible drugs in treating type 2 diabetes. The results of this study
      will be disseminated by a peer-reviewed publication. PROTOCOL REGISTRATION
      NUMBER: PROSPERO CRD42014010567.

PMID- 25762229
TI  - Comparative cardiovascular morbidity and mortality in patients taking different
      insulin regimens for type 2 diabetes: a systematic review.
AB  - OBJECTIVES: To summarise the literature evaluating the association between
      different insulin regimens and the incidence of cardiovascular morbidity and
      mortality in adults with type 2 diabetes. DESIGN: Systematic review. METHODS:
      Multiple biomedical databases (The Cochrane Library, PubMed, EMBASE, and
      International Pharmaceutical Abstracts) were searched from their inception to
      February 2014. References of included studies were hand searched. Randomised
      controlled trials (RCTs), cohort studies or case-control studies examining adults
      (>=18 years) with type 2 diabetes taking any type, dose and/or regimen of insulin
      were eligible for inclusion in this review. OUTCOME MEASURES: Primary outcomes
      were cardiovascular morbidity and mortality including fatal and/or non-fatal
      myocardial infarction, fatal and/or non-fatal stroke, major adverse cardiac
      events and cardiovascular death. All-cause mortality was assessed as a secondary
      outcome. RESULTS: Of the 3122 studies identified, 2 RCTs and 6 cohort studies
      were selected. No case-control studies met the inclusion criteria. The studies
      examined a total of 109,910 patients. Quantitative synthesis of the results from
      included studies was not possible due to a large amount of clinical
      heterogeneity. Each study evaluated cardiovascular outcomes across different
      insulin-exposure contrasts. RCTs did not identify any difference in
      cardiovascular risks among a fixed versus variable insulin regimen, or a prandial
      versus basal regimen, albeit clinically important risks and benefits cannot be
      ruled out due to wide CIs. Findings from cohort studies were variable with an
      increased and decreased risk of cardiovascular events and all-cause mortality
      being reported. CONCLUSIONS: This systematic review of randomised and non
      randomised studies identifies a substantive gap in the literature surrounding the
      cardiovascular morbidity and mortality of patients using different regimens of
      insulin. There is a need for more consistent high-quality evidence investigating
      the impact of insulin use on cardiovascular outcomes in patients with type 2
      diabetes. TRIAL REGISTRATION NUMBER:  PROSPERO: CRD42014007631.

PMID- 25762230
TI  - Disease history and risk of comorbidity in women's life course: a comprehensive
      analysis of the Japan Nurses' Health Study baseline survey.
AB  - OBJECTIVE: To classify diseases based on age at peak incidence to identify risk
      factors for later disease in women's life course. DESIGN: A cross-sectional
      baseline survey of participants in the Japan Nurses' Health Study. SETTING: A
      nationwide prospective cohort study on the health of Japanese nurses. The
      baseline survey was conducted between 2001 and 2007 (n=49,927). MAIN OUTCOME
      MEASURES: Age at peak incidence for 20 diseases from a survey of Japanese women
      was estimated using the Kaplan-Meier method with the Kernel smoothing technique.
      The incidence rate and peak incidence for diseases whose peak incidence occurred
      before the age of 45 years or before the perimenopausal period were selected as
      early-onset diseases. The OR and 95% CI were estimated to examine the risk of
      comorbidity between early-onset and other diseases. RESULTS: Four early-onset
      diseases (endometriosis, anaemia, migraine headache and uterine myoma) were
      significantly correlated with one another. Late-onset diseases significantly
      associated (OR>2) with early-onset diseases included comorbid endometriosis with
      ovarian cancer (3.65 (2.16 to 6.19)), endometrial cancer (2.40 (1.14 to 5.04))
      and cerebral infarction (2.10 (1.15 to 3.85)); comorbid anaemia with gastric
      cancer (3.69 (2.68 to 5.08)); comorbid migraine with transient ischaemic attack
      (3.06 (2.29 to 4.09)), osteoporosis (2.11 (1.71 to 2.62)), cerebral infarction
      (2.04 (1.26 to 3.30)) and angina pectoris (2.00 (1.49 to 2.67)); and comorbid
      uterine myoma with colorectal cancer (2.31 (1.48 to 3.61)). CONCLUSIONS: While
      there were significant associations between four early-onset diseases, women with
      a history of one or more of the early-onset diseases had a higher risk of other
      diseases later in their life course. Understanding the history of early-onset
      diseases in women may help reduce the subsequent risk of chronic diseases in
      later life.

PMID- 25762231
TI  - Using a mass media campaign to raise women's awareness of the link between
      alcohol and cancer: cross-sectional pre-intervention and post-intervention
      evaluation surveys.
AB  - OBJECTIVES: To evaluate the effectiveness of a population-based, statewide public
      health intervention designed to improve women's awareness and knowledge of the
      link between alcohol and cancer. DESIGN: Cross-sectional tracking surveys
      conducted pre-intervention and post-intervention (waves I and III of campaign).
      SETTING: Western Australia. PARTICIPANTS: Cross-sectional samples of Western
      Australian women aged 25-54 years before the campaign (n=136) and immediately
      after wave I (n=206) and wave III (n=155) of the campaign. INTERVENTION: The
      'Alcohol and Cancer' mass media campaign ran from May 2010 to May 2011 and
      consisted of three waves of paid television advertising with supporting print
      advertisements. MAIN OUTCOME MEASURES: Campaign awareness; knowledge of drinking
      guidelines and the link between alcohol and cancer; intentions towards drinking.
      RESULTS: Prompted recognition of the campaign increased from 67% following wave I
      to 81% following wave III (adjusted OR (adj OR)=2.31, 95% CI 1.33 to 4.00,
      p=0.003). Improvements in women's knowledge that drinking alcohol on a regular
      basis increases cancer risk were found following wave I (adj OR=2.60, 95% CI 1.57
      to 4.30, p<0.001) and wave III (adj OR=4.88, 95% CI 2.55 to 9.36, p<0.001)
      compared with baseline. Knowledge of the recommended number of standard drinks
      for low risk in the long term increased between baseline and wave I (adj OR=1.68,
      95% CI 1.02 to 2.76, p=0.041), but not baseline and wave III (adj OR=1.42, 95% CI
      0.84 to 2.39, p=0.191). Among women who drink alcohol, the proportion expressing
      intentions to reduce alcohol consumption increased significantly between baseline
      and wave III (adj OR=2.38, 95% CI 1.11 to 5.12, p=0.026). However, no significant
      reductions in recent drinking behaviour were found following the campaign.
      CONCLUSIONS: Results indicate a population-based mass media campaign can reach
      the target audience and raise awareness of links between alcohol and cancer, and
      knowledge of drinking guidelines. However, a single campaign may be insufficient
      to measurably curb drinking behaviour in a culture where pro-alcohol social norms
      and product marketing are pervasive.

PMID- 25762233
TI  - Out-of-hours and weekend admissions to Danish medical departments: admission
      rates and 30-day mortality for 20 common medical conditions.
AB  - OBJECTIVES: Knowledge on timing of admissions and mortality for acute medical
      patients is limited. The aim of the study was to examine hospital admission rates
      and mortality rates for patients with common medical conditions according to time
      of admission. DESIGN: Nationwide population-based cohort study. SETTING:
      Population of Denmark. PARTICIPANTS: Using the Danish National Registry of
      Patients covering all Danish hospitals, we identified all adults with the first
      acute admission to a medical department in Denmark during 2010. PRIMARY AND
      SECONDARY OUTCOME MEASURES: Hourly admission rates and age-standardised and sex
      standardised 30-day mortality rates comparing weekday office hours, weekday out
      of hours, weekend daytime hours and weekend night-time hours. RESULTS: In total,
      174,192 acute medical patients were included in the study. The admission rates
      (patients per hour) were 38.7 (95% CI 38.4 to 38.9) during weekday office hours,
      13.3 (95% CI 13.2 to 13.5) during weekday out of hours, 19.8 (95% CI 19.6 to
      20.1) during weekend daytime hours and 7.9 (95% CI 7.8 to 8.0) during weekend
      night-time hours. Admission rates varied between medical conditions. The
      proportion of patients admitted to an intensive care unit (ICU) increased outside
      of office hours. The age-standardised and sex-standardised 30-day mortality rate
      was 5.1% (95% CI 5.0% to 5.3%) after admission during weekday office hours, 5.7%
      (95% CI 5.5% to 6.0%) after admission during weekday out of hours, 6.4% (95% CI
      6.1% to 6.7%) after admission during weekend daytime hours and 6.3% (95% CI 5.9%
      to 6.8%) after admission during weekend night-time hours. For the majority of the
      medical conditions examined, weekend admission was associated with highest
      mortality. CONCLUSIONS: While admission rates decreased from office hours to
      weekend hours there was an observed increase in mortality. This may reflect
      differences in severity of illness as the proportion admitted to an ICU increased
      during the weekend.

PMID- 25762232
TI  - Daptomycin plus fosfomycin versus daptomycin monotherapy in treating MRSA:
      protocol of a multicentre, randomised, phase III trial.
AB  - INTRODUCTION: Despite the availability of new antibiotics such as daptomycin,
      methicillin-resistant Staphylococcus aureus (MRSA) bacteraemia continues to be
      associated with high clinical failure rates. Combination therapy has been
      proposed as an alternative to improve outcomes but there is a lack of clinical
      studies. The study aims to demonstrate that combination of daptomycin plus
      fosfomycin achieves higher clinical success rates in the treatment of MRSA
      bacteraemia than daptomycin alone. METHODS AND ANALYSIS: A multicentre open
      label, randomised phase III study. Adult patients hospitalised with MRSA
      bacteraemia will be randomly assigned (1:1) to group 1: daptomycin 10 mg/kg/24 h
      intravenous; or group 2: daptomycin 10 mg/kg/24 h intravenous plus fosfomycin 2
      gr/6 g intravenous. The main outcome will be treatment response at week 6 after
      stopping therapy (test-of-cure (TOC) visit). This is a composite variable with
      two values: Treatment success: resolution of clinical signs and symptoms
      (clinical success) and negative blood cultures (microbiological success) at the
      TOC visit. Treatment failure: if any of the following conditions apply: (1) lack
      of clinical improvement at 72 h or more after starting therapy; (2) persistent
      bacteraemia (positive blood cultures on day 7); (3) therapy is discontinued early
      due to adverse effects or for some other reason based on clinical judgement; (4)
      relapse of MRSA bacteraemia before the TOC visit; (5) death for any reason before
      the TOC visit. Assuming a 60% cure rate with daptomycin and a 20% difference in
      cure rates between the two groups, 103 patients will be needed for each group
      (alpha:0.05, beta: 0.2). Statistical analysis will be based on intention to
      treat, as well as per protocol and safety analysis. ETHICS AND DISSEMINATION: The
      protocol was approved by the Spanish Medicines and Healthcare Products Regulatory
      Agency (AEMPS). The sponsor commits itself to publishing the data in first
      quartile peer-review journals within 12 months of the completion of the study.
      TRIAL REGISTRATION NUMBER: NCT01898338.

PMID- 25762234
TI  - Effects of electroconvulsive therapy on cognitive functioning in patients with
      depression: protocol for a systematic review and meta-analysis.
AB  - INTRODUCTION: Depression is the leading cause of disability worldwide, affecting
      approximately 350 million people. Evidence indicates that only 60-70% of persons
      with major depressive disorder who tolerate antidepressants respond to first-line
      drug treatment; the remainder become treatment resistant. Electroconvulsive
      therapy (ECT) is considered an effective therapy in persons with treatment
      resistant depression. The use of ECT is controversial due to concerns about
      temporary cognitive impairment in the acute post-treatment period. We will
      conduct a meta-analysis to examine the effects of ECT on cognition in persons
      with depression. METHODS: This systematic review and meta-analysis has been
      registered with PROSPERO (registration number: CRD42014009100). We developed our
      methods following the Preferred Reporting Items for Systematic Reviews and Meta
      Analysis (PRISMA) statement. We are searching MEDLINE, PsychINFO, EMBASE, CINAHL
      and Cochrane from the date of database inception to the end of October 2014. We
      are also searching the reference lists of published reviews and evidence reports
      for additional citations. Comparative studies (randomised controlled trials,
      cohort and case-control) published in English will be included in the meta
      analysis. Three clinical neuropsychologists will group the cognitive tests in
      each included article into a set of mutually exclusive cognitive subdomains. The
      risk of bias of randomised controlled trials will be assessed using the Jadad
      scale. We will supplement the Jadad scale with additional questions based on the
      Cochrane risk of bias tool. The risk of bias of cohort and case-control studies
      will be assessed using the Newcastle-Ottawa Scale. We will employ the Grading of
      Recommendations Assessment, Development, and Evaluation (GRADE) to assess the
      strength of evidence. STATISTICAL ANALYSIS: Separate meta-analyses will be
      conducted for each ECT treatment modality and cognitive subdomain using
      Comprehensive Meta-Analysis V.2.0.

PMID- 25762235
TI  - Large discrepancies in linezolid use between French teaching hospitals: A comment
      on "Antimicrobial stewardship and linezolid".

PMID- 25762236
TI  - Sphingosine-1-phosphate receptor subtype 2 signaling in endothelial senescence
      associated functional impairments and inflammation.
AB  - Endothelial inflammation is an important risk factor in the initiation and
      development of vascular disease. Therefore, signaling cascades and patho
      physiological outcomes of endothelial inflammation are important questions in
      vascular biology. Recent studies suggest that sphingosine-1-phosphate receptor
      subtype 2 (S1PR2) signaling in endothelial cells (ECs) play a critical role in
      endothelial inflammation. For example, ECs present in atherosclerotic plaques
      exhibit senescence phenotype. Levels of S1PR2 are markedly increased in cultured
      senescent ECs and in lesion regions of atherosclerotic endothelium. Also,
      inflammatory cytokines and mechanical flow stress profoundly increase S1PR2
      levels in ECs. Inhibition of endothelial S1PR2 signaling diminishes endothelial
      senescence-associated functional impairments and atherogenic stimuli-induced
      endothelial activation. In contrast, activation of endothelial S1PR2 stimulates
      the production of pro-inflammatory chemokines/cytokines and lipid mediators in
      ECs. In this article, we will review signaling and functions of sphingosine-1
      phosphate (S1P) receptors in endothelial biology, with particular focus on
      endothelial S1PR2 signaling-mediated endothelial inflammation. 

PMID- 25762237
TI  - Genetic and Environmental Influences on Obesity-Related Phenotypes in Chinese
      Twins Reared Apart and Together.
AB  - The relative importance of genetic and environmental influences on obesity
      related phenotypes remains unclear, and few studies have targeted the Chinese
      population. Here, we used Chinese twins reared apart and together to explore
      genetic and environmental influences on body mass index (BMI), waist
      circumference (WC) and waist-height ratio (WHtR), further to differentiate
      phenotype heritability between different age groups and genders separately and to
      differentiate influences of rearing environment and correlated environment.
      Phenotype heritability was calculated using the structural equation model in
      11,401 twin pairs aged 25-85 years. BMI (0.70, 95 % confidence interval (CI) 0.66
      0.74) of the total population was highly heritable, while WC (0.53, 95 %CI 0.50
      0.57) and WHtR (0.48, 95 %CI 0.45-0.51) were moderately heritable. Age and gender
      stratified analyses found higher heritability in the younger group and males than
      the older group and females. The correlated environment had a greater influence
      on the phenotypes than the rearing environment, especially on WC and WHtR,
      indicating that more correlated environment actions should be taken to prevent
      the rising trend of abdominal obesity.

PMID- 25762238
TI  - Fatty acid composition indicating diverse habitat use in coral reef fishes in the
      Malaysian South China Sea.
AB  - BACKGROUND: In order to understand feeding ecology and habitat use of coral reef
      fish, fatty acid composition was examined in five coral reef fishes, Thalassoma
      lunare, Lutjanus lutjanus, Abudefduf bengalensis, Scarus rivulatus and Scolopsis
      affinis collected in the Bidong Island of Malaysian South China Sea. RESULTS:
      Proportions of saturated fatty acids (SAFA) ranged 57.2% 74.2%, with the highest
      proportions in fatty acids, the second highest was monounsaturated fatty acids
      (MUFA) ranged from 21.4% to 39.0% and the proportion of polyunsaturated fatty
      acids (PUFA) was the lowest ranged from 2.8% to 14.1%. Each fatty acid
      composition differed among fishes, suggesting diverse feeding ecology, habitat
      use and migration during the fishes' life history in the coral reef habitats.
      CONCLUSIONS: Diets of the coral fish species might vary among species in spite of
      that each species are living sympatrically. Differences in fatty acid profiles
      might not just be considered with respect to the diets, but might be based on the
      habitat and migration.

PMID- 25762241
TI  - Abstracts of the 21st Annual Scientific Conference of the Society on NeuroImmune
      Pharmacology, April 22-25, 2015, Miami, Florida.

PMID- 25762239
TI  - Physicochemical evolution and molecular adaptation of the cetacean osmoregulation
      related gene UT-A2 and implications for functional studies.
AB  - Cetaceans have an enigmatic evolutionary history of re-invading aquatic habitats.
      One of their essential adaptabilities that has enabled this process is their
      homeostatic strategy adjustment. Here, we investigated the physicochemical
      evolution and molecular adaptation of the cetacean urea transporter UT-A2, which
      plays an important role in urine concentration and water homeostasis. First, we
      cloned UT-A2 from the freshwater Yangtze finless porpoise, after which
      bioinformatics analyses were conducted based on available datasets (including
      freshwater baiji and marine toothed and baleen whales) using MEGA, PAML,
      DataMonkey, TreeSAAP and Consurf. Our findings suggest that the UT-A2 protein
      shows folding similar to that of dvUT and UT-B, whereas some variations occurred
      in the functional So and Si regions of the selectivity filter. Additionally,
      several regions of the cetacean UT-A2 protein have experienced molecular
      adaptations. We suggest that positive-destabilizing selection could contribute to
      adaptations by influencing its biochemical and conformational character. The
      conservation of amino acid residues within the selectivity filter of the urea
      conduction pore is likely to be necessary for urea conduction, whereas the non
      conserved amino acid replacements around the entrance and exit of the conduction
      pore could potentially affect the activity, which could be interesting target
      sites for future mutagenesis studies. 

PMID- 25762240
TI  - Open Mesh Repair for Inguinal Hernia is Safer than Laparoscopic Repair or Open
      Non-mesh Repair: A Nationwide Registry Study of Complications.
AB  - BACKGROUND: Inguinal hernia repair is the most common elective procedure in
      general surgery. Therefore, the number of patients having complications related
      to inguinal hernia surgery is relatively large. The aim of this study was to
      compare complication profiles of inguinal open mesh (OM) hernioplasties with open
      non-mesh (OS) repairs and laparoscopic (LAP) repairs using retrospective
      nationwide registry data. METHODS: The database of the Finnish Patient Insurance
      Centre (FPIC) was searched for complications of inguinal and femoral hernia
      repairs during 2002-2010. Complications of OM repairs were compared to
      complications of OS repairs and LAP repairs. RESULTS: Over 75 % of all inguinal
      hernia procedures during the study period in Finland were OM hernioplasties. FPIC
      received 245 complication reports after OM repairs, 40 after OS repairs, and 50
      after LAP repairs. Reported complications were significantly more severe after
      LAP and OS repairs than OM surgery (p<0.001). Visceral complications (p<0.001),
      deep infections (p<0.001), and deep hemorrhagic complications (p<0.001) were
      overrepresented in the LAP group. In the OS group, visceral complications
      (p<0.001), recurrences (p<0.001), and severe neuropathic pain (p<0.001)
      predominated. CONCLUSION: LAP and OS repairs of inguinal hernia were associated
      with more severe complications than open surgery with mesh in this study.

PMID- 25762242
TI  - Surgical stress response after colorectal resection: a comparison of robotic,
      laparoscopic, and open surgery.
AB  - BACKGROUND: The perioperative immune status of colorectal robotic surgery (RS),
      laparoscopic surgery (LS), and open surgery (OS) patients has not been compared.
      Our aim was to evaluate perioperative stress and immune response after RS, LS and
      OS. METHODS: This prospective study included 46 colorectal surgery patients from
      the Department of Surgical Oncology of the University of Tokyo Hospital.
      Peripheral venous blood samples were obtained preoperatively and on postoperative
      days 1, 3, and 6. We evaluated expression of HLA-DR (marker of immune
      competence), C-reactive protein (CRP) levels, and lymphocyte subset counts
      (natural killers, cytotoxic T cells and helper T cells). RESULTS: Fifteen, 23,
      and 8 patients underwent RS, LS and OS, respectively. HLA-DR expression was the
      lowest on day 1 and gradually increased on days 3 and 6 in all the groups. There
      was no significant difference in postoperative HLA-DR expression between the RS
      and LS group. However, on day 3, HLA-DR expression in the RS group was
      significantly higher than in the OS group (p = 0.04). On day 1, CRP levels in the
      LS group were significantly lower than in the RS group (p = 0.038). There were no
      significant perioperative changes in the lymphocyte subset cell count between the
      three groups. CONCLUSIONS: Perioperative surgical stress, as evaluated by
      immunological parameters, was comparable between robotic and laparoscopic surgery
      and higher with open surgery. Robotic surgery may be an alternative to
      laparoscopic surgery, as a minimally invasive surgery option for colorectal
      cancer.

PMID- 25762244
TI  - All in good time.

PMID- 25762245
TI  - An array of problems.

PMID- 25762243
TI  - Self-induced parametric amplification arising from nonlinear elastic coupling in
      a micromechanical resonating disk gyroscope.
AB  - Parametric amplification, resulting from intentionally varying a parameter in a
      resonator at twice its resonant frequency, has been successfully employed to
      increase the sensitivity of many micro- and nano-scale sensors. Here, we
      introduce the concept of self-induced parametric amplification, which arises
      naturally from nonlinear elastic coupling between the degenerate vibration modes
      in a micromechanical disk-resonator, and is not externally applied. The device
      functions as a gyroscope wherein angular rotation is detected from Coriolis
      coupling of elastic vibration energy from a driven vibration mode into a second
      degenerate sensing mode. While nonlinear elasticity in silicon resonators is
      extremely weak, in this high quality-factor device, ppm-level nonlinear elastic
      effects result in an order-of-magnitude increase in the observed sensitivity to
      Coriolis force relative to linear theory. Perfect degeneracy of the primary and
      secondary vibration modes is achieved through electrostatic frequency tuning,
      which also enables the phase and frequency of the parametric coupling to be
      varied, and we show that the resulting phase and frequency dependence of the
      amplification follow the theory of parametric resonance. We expect that this
      phenomenon will be useful for both fundamental studies of dynamic systems with
      low dissipation and for increasing signal-to-noise ratio in practical
      applications such as gyroscopes. 

PMID- 25762246
TI  - In the beginning.

PMID- 25762247
TI  - Help to fight the battle for Earth in US schools.

PMID- 25762259
TI  - Flu genomes trace H7N9 evolution.

PMID- 25762260
TI  - Mistrust and meddling unsettles US science agency.

PMID- 25762261
TI  - DNA clock proves tough to set.

PMID- 25762263
TI  - LHC 2.0: A new view of the Universe.

PMID- 25762262
TI  - World's whaling slaughter tallied.

PMID- 25762264
TI  - Anthropocene: The human age.

PMID- 25762265
TI  - Conflict resolution: Wars without end.

PMID- 25762266
TI  - Global change: Put people at the centre of global risk management.

PMID- 25762270
TI  - Reproducibility: Stamp out shabby research conduct.

PMID- 25762271
TI  - Lab training: Undergraduate research in action.

PMID- 25762272
TI  - Financial markets: Tax transactions to stabilize trading.

PMID- 25762273
TI  - Denmark: Women's grants lost in inequality ocean.

PMID- 25762274
TI  - Bacteria: Assessing resistance to new antibiotics.

PMID- 25762275
TI  - Yves Chauvin (1930-2015).

PMID- 25762276
TI  - Planetary science: Enceladus' hot springs.

PMID- 25762278
TI  - Climate change: Black carbon and atmospheric feedbacks.

PMID- 25762279
TI  - Evolutionary biology: The origin of terrestrial hearing.

PMID- 25762280
TI  - Defining the anthropocene.
AB  - Time is divided by geologists according to marked shifts in Earth's state. Recent
      global environmental changes suggest that Earth may have entered a new human
      dominated geological epoch, the Anthropocene. Here we review the historical
      genesis of the idea and assess anthropogenic signatures in the geological record
      against the formal requirements for the recognition of a new epoch. The evidence
      suggests that of the various proposed dates two do appear to conform to the
      criteria to mark the beginning of the Anthropocene: 1610 and 1964. The formal
      establishment of an Anthropocene Epoch would mark a fundamental change in the
      relationship between humans and the Earth system. 

PMID- 25762281
TI  - Ongoing hydrothermal activities within Enceladus.
AB  - Detection of sodium-salt-rich ice grains emitted from the plume of the Saturnian
      moon Enceladus suggests that the grains formed as frozen droplets from a liquid
      water reservoir that is, or has been, in contact with rock. Gravitational field
      measurements suggest a regional south polar subsurface ocean of about 10
      kilometres thickness located beneath an ice crust 30 to 40 kilometres thick.
      These findings imply rock-water interactions in regions surrounding the core of
      Enceladus. The resulting chemical 'footprints' are expected to be preserved in
      the liquid and subsequently transported upwards to the near-surface plume
      sources, where they eventually would be ejected and could be measured by a
      spacecraft. Here we report an analysis of silicon-rich, nanometre-sized dust
      particles (so-called stream particles) that stand out from the water-ice
      dominated objects characteristic of Saturn. We interpret these grains as
      nanometre-sized SiO2 (silica) particles, initially embedded in icy grains emitted
      from Enceladus' subsurface waters and released by sputter erosion in Saturn's E
      ring. The composition and the limited size range (2 to 8 nanometres in radius) of
      stream particles indicate ongoing high-temperature (>90  degrees C) hydrothermal
      reactions associated with global-scale geothermal activity that quickly
      transports hydrothermal products from the ocean floor at a depth of at least 40
      kilometres up to the plume of Enceladus. 

PMID- 25762283
TI  - Shedding of clinical-grade lentiviral vectors is not detected in a gene therapy
      setting.
AB  - Gene therapy using viral vectors that stably integrate into ex vivo cultured
      cells holds great promises for the treatment of monogenic diseases as well as
      cancer. However, carry-over of infectious vector particles has been described to
      occur upon ex vivo transduction of target cells. This, in turn, may lead to
      inadvertent spreading of viral particles to off-target cells in vivo, raising
      concerns for potential adverse effects, such as toxicity of ectopic transgene
      expression, immunogenicity from in vivo transduced antigen-presenting cells and,
      possibly, gene transfer to germline cells. Here, we have investigated factors
      influencing the extent of lentiviral vector (LV) shedding upon ex vivo
      transduction of human hematopoietic stem and progenitor cells. Our results
      indicate that, although vector carry-over is detectable when using laboratory
      grade vector stocks, the use of clinical-grade vector stocks strongly decreases
      the extent of inadvertent transduction of secondary targets, likely because of
      the higher degree of purification. These data provide supportive evidence for the
      safe use of the LV platform in clinical settings. 

PMID- 25762285
TI  - Electronic structural basis for the atomic partial charges of planar molecular
      systems derived from out-of-plane dipole derivatives.
AB  - The method of deriving atomic partial charges from out-of-plane dipole
      derivatives has gained renewed interest as a useful method for identifying the
      changes in charge distribution upon molecular motion. To understand the nature of
      those atomic partial charges and to explore possible wide applicability of this
      method, the modulations in the electron density induced by out-of-plane atomic
      displacements are analyzed by calculating two-dimensional electronic polarization
      derivatives. It is shown that their amplitudes are substantially delocalized to
      the spatial regions of the adjacent atoms, suggesting the size of the planar
      region required for applying this method to locally planar systems, such as the
      peptide group capped by alkyl groups. It is also shown that, in molecular
      complexes, the amplitudes of electronic polarization derivatives are affected
      rather strongly by the polarization effect, indicating the way to use this method
      to estimate the extent of intermolecular charge transfer in hydrogen-bonded
      systems. 

PMID- 25762284
TI  - Site promiscuity of coliphage HK022 integrase as a tool for gene therapy.
AB  - The integrase (Int) encoded by the lambdoid coliphage HK022 targets in its host
      chromosome a 21 base pair (bp) recombination site termed attB or BOB'. attB
      comprises two 7 bp partially inverted (palindromic) Int-binding sites of 7 bp
      each termed B and B'. B and B' flank a central 7 bp crossover site or 'overlap'
      (O). We show that replacing O with a random 7 bp sequence supports Int-mediated
      site-specific recombination as long as the cognate and larger phage recombination
      site attP features an identical O sequence. This promiscuity allowed us to
      identify on the human genome several native active secondary attB sites ('attB')
      with random overlaps that flank human deleterious mutations, raising the prospect
      of using such sites to cure the 'attB'-flanked mutations by Int-catalyzed RMCE
      (recombinase-mediated cassette exchange) reactions. An analysis of such active
      and inactive 'attB's suggested a minimal 14-15 bp attB consensus sequence
      (instead of the 21 bp) with a reduced 3 bp palindrome.

PMID- 25762287
TI  - Higher Mortality in registrants with sudden model for end-stage liver disease
      increase: Disadvantaged by the current allocation policy.
AB  - Liver allocation is based on current Model for End-Stage Liver Disease (MELD)
      scores, with priority in the case of a tie being given to those waiting the
      longest with a given MELD score. We hypothesized that this priority might not
      reflect risk: registrants whose MELD score has recently increased receive lower
      priority but might have higher wait-list mortality. We studied wait-list and
      posttransplant mortality in 69,643 adult registrants from 2002 to 2013. By
      likelihood maximization, we empirically defined a MELD spike as a MELD increase
      >= 30% over the previous 7 days. At any given time, only 0.6% of wait-list
      patients experienced a spike; however, these patients accounted for 25% of all
      wait-list deaths. Registrants who reached a given MELD score after a spike had
      higher wait-list mortality in the ensuing 7 days than those with the same
      resulting MELD score who did not spike, but they had no difference in
      posttransplant mortality. The spike-associated wait-list mortality increase was
      highest for registrants with medium MELD scores: specifically, 2.3-fold higher
      (spike versus no spike) for a MELD score of 10, 4.0-fold higher for a MELD score
      of 20, and 2.5-fold higher for a MELD score of 30. A model incorporating the MELD
      score and spikes predicted wait-list mortality risk much better than a model
      incorporating only the MELD score. Registrants with a sudden MELD increase have a
      higher risk of short-term wait-list mortality than is indicated by their current
      MELD score but have no increased risk of posttransplant mortality; allocation
      policy should be adjusted accordingly.

PMID- 25762286
TI  - Cerebellar output controls generalized spike-and-wave discharge occurrence.
AB  - OBJECTIVE: Disrupting thalamocortical activity patterns has proven to be a
      promising approach to stop generalized spike-and-wave discharges (GSWDs)
      characteristic of absence seizures. Here, we investigated to what extent
      modulation of neuronal firing in cerebellar nuclei (CN), which are anatomically
      in an advantageous position to disrupt cortical oscillations through their
      innervation of a wide variety of thalamic nuclei, is effective in controlling
      absence seizures. METHODS: Two unrelated mouse models of generalized absence
      seizures were used: the natural mutant tottering, which is characterized by a
      missense mutation in Cacna1a, and inbred C3H/HeOuJ. While simultaneously
      recording single CN neuron activity and electrocorticogram in awake animals, we
      investigated to what extent pharmacologically increased or decreased CN neuron
      activity could modulate GSWD occurrence as well as short-lasting, on-demand CN
      stimulation could disrupt epileptic seizures. RESULTS: We found that a subset of
      CN neurons show phase-locked oscillatory firing during GSWDs and that
      manipulating this activity modulates GSWD occurrence. Inhibiting CN neuron action
      potential firing by local application of the gamma-aminobutyric acid type A (GABA
      A) agonist muscimol increased GSWD occurrence up to 37-fold, whereas increasing
      the frequency and regularity of CN neuron firing with the use of GABA-A
      antagonist gabazine decimated its occurrence. A single short-lasting (30-300
      milliseconds) optogenetic stimulation of CN neuron activity abruptly stopped
      GSWDs, even when applied unilaterally. Using a closed-loop system, GSWDs were
      detected and stopped within 500 milliseconds. INTERPRETATION: CN neurons are
      potent modulators of pathological oscillations in thalamocortical network
      activity during absence seizures, and their potential therapeutic benefit for
      controlling other types of generalized epilepsies should be evaluated.

PMID- 25762288
TI  - Neurocognitive effects of estrogens across the adult lifespan in nonhuman
      primates: State of knowledge and new perspectives.
AB  - This article is part of a Special Issue "Estradiol and cognition". This review
      discusses the unique contribution of nonhuman primate research to our
      understanding of the neurocognitive effects of estrogens throughout the adult
      lifespan in females. Mounting evidence indicates that estrogens affect many
      aspects of hippocampal, prefrontal and cholinergic function in the primate brain
      and the underlying mechanisms are beginning to be elucidated. In addition,
      estrogens may also influence cognitive function indirectly, via the modulation of
      other systems that impact cognition. We will focus on the effects of estrogens on
      sleep and emphasize the need for primate models to better understand these
      complex interactions. Continued research with nonhuman primates is essential for
      the development of therapies that are optimal for the maintenance of women's
      cognitive health throughout the lifespan. 

PMID- 25762290
TI  - A human colonic crypt culture system to study regulation of stem cell-driven
      tissue renewal and physiological function.
AB  - The intestinal epithelium is one of the most rapidly renewing tissues in the
      human body and fulfils vital physiological roles such as barrier function and
      transport of nutrients and fluid. Investigation of gut epithelial physiology in
      health and disease has been hampered by the lack of ex vivo models of the native
      human intestinal epithelium. Recently, remarkable progress has been made in
      defining intestinal stem cells and in generating intestinal organoid cultures. In
      parallel, we have developed a 3D culture system of the native human colonic
      epithelium that recapitulates the topological hierarchy of stem cell-driven
      tissue renewal and permits the physiological study of native polarized epithelial
      cells. Here we describe methods to establish 3D cultures of intact human colonic
      crypts and conduct real-time imaging of intestinal tissue renewal, cellular
      signalling, and physiological function, in conjunction with manipulation of gene
      expression by lentiviral or adenoviral transduction. Visualization of mRNA- and
      protein-expression patterns in cultured human colonic crypts, and cross
      validation with crypts derived from fixed mucosal biopsies, is also described.
      Alongside studies using intestinal organoids, the near-native human colonic crypt
      culture model will help to bridge the gap that exists between investigation of
      colon cancer cell lines and/or animal (tissue) studies, and progression to
      clinical trials. To this end, the near native human colonic crypt model provides
      a platform to aid the development of novel strategies for the prevention of
      inflammatory bowel disease and cancer. 

PMID- 25762289
TI  - Low birthweight, gestational age, need for surgical intervention and gram
      negative bacteraemia predict intestinal failure following necrotising
      enterocolitis.
AB  - AIM: Necrotising enterocolitis (NEC) is associated with high morbidity and
      mortality. The aim of this study was to identify predictors of intestinal failure
      (IF), morbidity and mortality following NEC. METHODS: We performed a
      retrospective study of all neonates treated for NEC stage II or greater at a
      tertiary referral NICU between 2000 and 2009. Demographic data, need for surgery,
      residual bowel length and rates of bacteraemia, cholestasis, IF and mortality
      were analysed. RESULTS: During the 10-year period, 301 patients were referred
      with NEC and 152 had surgical intervention. Overall mortality was 32%. Of the 230
      infants who survived >42 days, 97 (42%) had IF at 42 days, decreasing to 15% at
      >90 days. The rate of IF was significantly higher in the surgical group than the
      medical group (OR 2.04, 95% CI, 1.25-3.35, p < 0.004), but 23% of the medically
      treated infants with NEC also developed IF. There was a significant relationship
      between IF and gram-negative bacteraemia, the need for surgery, cholestasis,
      liver failure and mortality. CONCLUSION: Intestinal failure occurred in a
      significant proportion of infants with NEC. Predictors for IF among infants with
      NEC were low birthweight, low gestational age, need for surgical intervention and
      gram-negative bacteraemia.

PMID- 25762291
TI  - Generation of Embryonic Stem Cells in Rabbits.
AB  - Here we have described a procedure to generate embryonic stem cell (ESC) lines
      from rabbit preimplantation blastocysts. We have also provided detailed
      procedures to characterize the resulting ESC lines, such as the analysis of
      pluripotency marker expression by reverse transcription quantitative polymerase
      chain reaction, immunolabeling, and fluorescence-associated cell sorting;
      evaluation of pluripotency by teratoma production; and assessment of genetic
      stability by karyotyping. 

PMID- 25762292
TI  - Applying Shear Stress to Pluripotent Stem Cells.
AB  - Thorough understanding of the effects of shear stress on stem cells is critical
      for the rationale design of large-scale production of cell-based therapies. This
      is of growing importance as emerging tissue engineering and regenerative medicine
      applications drive the need for clinically relevant numbers of both pluripotent
      stem cells (PSCs) and cells derived from PSCs. Here, we describe the use of a
      custom parallel plate bioreactor system to impose fluid shear stress on a layer
      of PSCs adhered to protein-coated glass slides. This system can be useful both
      for basic science studies in mechanotransduction and as a surrogate model for
      bioreactors used in large-scale production.

PMID- 25762293
TI  - Generation of a Knockout Mouse Embryonic Stem Cell Line Using a Paired
      CRISPR/Cas9 Genome Engineering Tool.
AB  - CRISPR/Cas9, originally discovered as a bacterial immune system, has recently
      been engineered into the latest tool to successfully introduce site-specific
      mutations in a variety of different organisms. Composed only of the Cas9 protein
      as well as one engineered guide RNA for its functionality, this system is much
      less complex in its setup and easier to handle than other guided nucleases such
      as Zinc-finger nucleases or TALENs.Here, we describe the simultaneous
      transfection of two paired CRISPR sgRNAs-Cas9 plasmids, in mouse embryonic stem
      cells (mESCs), resulting in the knockout of the selected target gene. Together
      with a four primer-evaluation system, it poses an efficient way to generate new
      independent knockout mouse embryonic stem cell lines.

PMID- 25762294
TI  - 26S and PA28-20S Proteasome Activity in Cytosolic Extracts from Embryonic Stem
      Cells.
AB  - The proteasome is a complex multisubunit protease that plays a major role in the
      degradation of proteins in eukaryotic cells. Proteasome function is one of the
      key players regulating the proteome and it is vital for many cellular processes.
      The method described here makes it possible to assay the proteolytic capacities
      of proteasome complexes separately in crude cytosolic extracts from ES cells. The
      method is based on hydrolysis of a fluorogenic peptide substrate in lysates
      prepared under conditions that favor the interactions of the 20S proteasomal
      catalytical core with either the 19S or the PA28alphabeta proteasome regulator. 

PMID- 25762295
TI  - Pancreatic Differentiation from Murine Embryonic Stem Cells.
AB  - Pluripotent stem cells are considered as a cell source for replacement therapies
      for pancreatic beta cells and other organs.We identified tetrabenazine (TBZ),
      vesicular monoamine transporter 2 (VMAT2) inhibitor as a promoter of late-stage
      differentiation of Pdx1-positive pancreatic progenitor cells into Ngn3-positive
      endocrine progenitor cells. A cell-permeable cAMP analog, dBu-cAMP promotes beta
      cell maturation in late stage of differentiation. The induced beta cells can
      secrete insulin in a glucose-dependent manner.Our protocol consists of a three 
      step differentiation process. ES cell recapitulate embryonic developmental
      processes in vitro. Therefore, the ES cell differentiation system is a useful
      model for the understanding of molecular mechanism of beta-cell differentiation
      and are useful for application for future regenerative medicine.

PMID- 25762296
TI  - Differentiation of Adipocytes in Monolayer from Mouse Embryonic Stem Cells.
AB  - Obesity and its comorbidity incidence have increased worldwide during the past 10
      years. In consequence, researchers have drawn their attention to the
      understanding of adipocyte differentiation. Several cellular model systems have
      been established; however no efficient protocol could be developed so far to
      differentiate the pluripotent embryonic stem cells to adipocytes. In this
      chapter, we describe a detailed protocol that is optimized for mouse embryonic
      stem cells. The result of this differentiation is a homogenous adipocyte
      monolayer culture that can be used for several applications including
      developmental and pharmacological research. 

PMID- 25762297
TI  - Generation and Purification of Definitive Endoderm Cells Generated from
      Pluripotent Stem Cells.
AB  - Differentiation of pluripotent stem cells into cells of the definitive endoderm
      requires an in vitro gastrulation event. Differentiated somatic cells derived
      from this germ layer may then be used for cell replacement therapies of
      degenerative diseases of the liver, lung, and pancreas. Here we describe an
      endoderm differentiation protocol, which initiates the differentiation from a
      defined cell number of dispersed single cells and reliably yields in >70-80 %
      endoderm-committed cells in a short 5-day treatment regimen.

PMID- 25762298
TI  - Gene Transfer into Pluripotent Stem Cells via Lentiviral Transduction.
AB  - Recombinant lentiviral vectors are powerful tools to stably manipulate human
      pluripotent stem cells. They can be used to deliver ectopic genes, shRNAs,
      miRNAs, or any possible genetic DNA sequence into diving and nondividing cells.
      Here we describe a general protocol for the production of self-inactivating
      lentiviral vector particles and their purification to high titers by either
      ultracentrifugation or ultrafiltration. Next we provide a basic procedure to
      transduce human pluripotent stem cells and propagate clonal cell lines. 

PMID- 25762299
TI  - Limbal Stromal Tissue Specific Stem Cells and Their Differentiation Potential to
      Corneal Epithelial Cells.
AB  - From the derivation of the first human embryonic stem (hES) cell line to the
      development of induced pluripotent stem (iPS) cells; it has become evident that
      tissue specific stem cells are able to differentiate into a specific somatic cell
      types. The understanding of key processes such as the signaling pathways and the
      role of the microenvironment in epidermal/epithelial development has provided
      important clues for the derivation of specific epithelial cell types.Various
      differentiation protocols/methods were used to attain specific epithelial cell
      types. Here, we describe in detail the procedure to follow for isolation of
      tissue specific stem cells, mimicking their microenvironment to attain stem cell
      characteristics, and their potential differentiation to corneal epithelial cells.

PMID- 25762300
TI  - Classification and Clustering on Microarray Data for Gene Functional Prediction
      Using R.
AB  - Gene expression data (microarrays and RNA-sequencing data) as well as other kinds
      of genomic data can be extracted from publicly available genomic data. Here, we
      explain how to apply multivariate cluster and classification methods on gene
      expression data. These methods have become very popular and are implemented in
      freely available software in order to predict the participation of gene products
      in a specific functional category of interest. Taking into account the
      availability of data and of these methods, every biological study should apply
      them in order to obtain knowledge on the organism studied and functional category
      of interest. A special emphasis is made on the nonlinear kernel classification
      methods. 

PMID- 25762301
TI  - Integrated Analysis of Transcriptomic and Proteomic Datasets Reveals Information
      on Protein Expressivity and Factors Affecting Translational Efficiency.
AB  - Integrated analysis of large-scale transcriptomic and proteomic data can provide
      important insights into the metabolic mechanisms underlying complex biological
      systems. In this chapter, we present methods to address two aspects of issues
      related to integrated transcriptomic and proteomic analysis. First, due to the
      fact that proteomic datasets are often incomplete, and integrated analysis of
      partial proteomic data may introduce significant bias. To address these issues,
      we describe a zero-inflated Poisson (ZIP)-based model to uncover the complicated
      relationships between protein abundances and mRNA expression levels, and then
      apply them to predict protein abundance for the proteins not experimentally
      detected. The ZIP model takes into consideration the undetected proteins by
      assuming that there is a probability mass at zero representing expressed proteins
      that were undetected owing to technical limitations. The model validity is
      demonstrated using biological information of operons, regulons, and pathways.
      Second, weak correlation between transcriptomic and proteomic datasets is often
      due to biological factors affecting translational processes. To quantify the
      effects of these factors, we describe a multiple regression-based statistical
      framework to quantitatively examine the effects of various translational
      efficiency-related sequence features on mRNA-protein correlation. Using the
      datasets from sulfate-reducing bacteria Desulfovibrio vulgaris, the analysis
      shows that translation-related sequence features can contribute up to 15.2-26.2%
      of the total variation of the correlation between transcriptomic and proteomic
      datasets, and also reveals the relative importance of various features in
      translation process.

PMID- 25762302
TI  - Bayesian accounts of covert selective attention: A tutorial review.
AB  - Decision making and optimal observer models offer an important theoretical
      approach to the study of covert selective attention. While their probabilistic
      formulation allows quantitative comparison to human performance, the models can
      be complex and their insights are not always immediately apparent. Part 1
      establishes the theoretical appeal of the Bayesian approach, and introduces the
      way in which probabilistic approaches can be applied to covert search paradigms.
      Part 2 presents novel formulations of Bayesian models of 4 important covert
      attention paradigms, illustrating optimal observer predictions over a range of
      experimental manipulations. Graphical model notation is used to present models in
      an accessible way and Supplementary Code is provided to help bridge the gap
      between model theory and practical implementation. Part 3 reviews a large body of
      empirical and modelling evidence showing that many experimental phenomena in the
      domain of covert selective attention are a set of by-products. These effects
      emerge as the result of observers conducting Bayesian inference with noisy
      sensory observations, prior expectations, and knowledge of the generative
      structure of the stimulus environment. 

PMID- 25762303
TI  - The complexities of keeping the beat: dynamical structure in the nested behaviors
      of finger tapping.
AB  - Recent research on fractal scaling in simple human behaviors (e.g., reaction time
      tasks) has demonstrated that different aspects of the performance (e.g., key
      presses and key releases) all reveal pink noise signals but yet are uncorrelated
      with one another in time. These studies have suggested that the independence of
      these signals might be due to the functional independence of these different sub
      actions, given the task constraints. The current experiments investigated whether
      under a different set of constraints (e.g., finger tapping with and without a
      metronome) nested sub-actions might show interrelated dynamics, and whether
      manipulations affecting the fractal scaling of one also might have consequences
      for the scaling of others. Experiment 1 revealed that the inter-tap intervals and
      key-press durations of participants' tapping behavior were dynamically related to
      one another and that the fractal scaling of both changed in the switch from self
      paced to metronome-paced tapping. Consistent with past research, the inter-tap
      intervals changed toward an antipersistent, blue noise pattern of variation, but
      the key-press durations became even more persistent. Experiment 2 revealed that
      this pattern of results could be altered by asking participants to attempt to
      hold the key down for the entire length of the metronome tone. Specifically, the
      key-press duration of participants in the "hold" group became less persistent in
      the switch across task conditions. Collectively, the results of these experiments
      suggest that fractal scaling reliably reflects the functional relationships of
      the processes underlying task performance. 

PMID- 25762304
TI  - Inferring the depth of 3-D objects from tactile spatial information.
AB  - Four psychophysical experiments were conducted to examine the relation between
      tactile spatial information and the estimated depth of partially touched 3-D
      objects. Human participants touched unseen, tactile grating patterns with their
      hand while keeping the hand shape flat. Experiment 1, by means of a production
      task, showed that the estimated depth of the concave part below the touched
      grating was well correlated with the separation between the elements of the
      grating, but not with the overall size of the grating, nor with the local
      structure of the touched parts. Experiments 2 and 3, by means of a haptic working
      memory task, showed that the remembered depth of a target surface was biased
      toward the estimated bottom position of a tactile grating distractor. Experiment
      4, by means of a discrimination task, revealed that tactile grating patterns
      influenced speeded judgments about visual 3-D shapes. These results suggest that
      the haptic system uses heuristics based on spatial information to infer the depth
      of an untouched part of a 3-D object. 

PMID- 25762307
TI  - Erratum to: The emerging framework of mammalian auditory hindbrain development.

PMID- 25762305
TI  - Systemic and mucosal immunity in mice elicited by a single immunization with
      human adenovirus type 5 or 41 vector-based vaccines carrying the spike protein of
      Middle East respiratory syndrome coronavirus.
AB  - An ideal vaccine against mucosal pathogens such as Middle East respiratory
      syndrome coronavirus (MERS-CoV) should confer sustained, protective immunity at
      both systemic and mucosal levels. Here, we evaluated the in vivo systemic and
      mucosal antigen-specific immune responses induced by a single intramuscular or
      intragastric administration of recombinant adenoviral type 5 (Ad5) or type 41
      (Ad41) -based vaccines expressing the MERS-CoV spike (S) protein. Intragastric
      administration of either Ad5-S or Ad41-S induced antigen-specific IgG and
      neutralizing antibody in serum; however, antigen-specific T-cell responses were
      not detected. In contrast, after a single intramuscular dose of Ad5-S or Ad41-S,
      functional antigen-specific T-cell responses were elicited in the spleen and
      pulmonary lymphocytes of the mice, which persisted for several months. Both rAd
      based vaccines administered intramuscularly induced systemic humoral immune
      responses (neutralizing IgG antibodies). Our results show that a single dose of
      Ad5-S- or Ad41-S-based vaccines represents an appealing strategy for the control
      of MERS-CoV infection and transmission. 

PMID- 25762306
TI  - The nuclear receptor nr4a1 controls CD8 T cell development through
      transcriptional suppression of runx3.
AB  - The NR4A nuclear receptor family member Nr4a1 is strongly induced in thymocytes
      undergoing selection, and has been shown to control the development of Treg
      cells; however the role of Nr4a1 in CD8(+) T cells remains undefined. Here we
      report a novel role for Nr4a1 in regulating the development and frequency of
      CD8(+) T cells through direct transcriptional control of Runx3. We discovered
      that Nr4a1 recruits the corepressor, CoREST to suppress Runx3 expression in
      CD8(+) T cells. Loss of Nr4a1 results in increased Runx3 expression in thymocytes
      which consequently causes a 2-fold increase in the frequency and total number of
      intrathymic and peripheral CD8(+) T cells. Our findings establish Nr4a1 as a
      novel and critical player in the regulation of CD8 T cell development through the
      direct suppression of Runx3. 

PMID- 25762308
TI  - Enhanced thermoelectric performance of bar-coated SWCNT/P3HT thin films.
AB  - The influence of processing conditions, such as ink concentration and coating
      method, on the thermoelectric properties of SWCNT/P3HT nanocomposite films was
      investigated systematically. Using simple wire-bar-coating, SWCNT/P3HT
      nanocomposite films with high thermoelectric performance could be obtained
      without additional P3HT doping. The wire-bar-coated SWCNT/P3HT nanocomposite
      films exhibited power factors of up to 105 MUW m(-1) K(-2) at room temperature.
      The SWCNT bundles with diameters in the range of 6-23 nm formed an interconnected
      network in the wire-bar-coated nanocomposite films. Network formation in these
      nanocomposite films was expected to be strongly related to the development of
      electrical pathways due to inter-SWCNT bundle connections. This study suggests
      that the thermoelectric performance of SWCNT/P3HT nanocomposite films could be
      optimized by controlling their processing conditions and morphology. 

PMID- 25762309
TI  - Changing epidemiology of hepatitis C virus genotypes in the central region of
      Argentina.
AB  - The aim of this study was to analyze the prevalence of hepatitis C virus (HCV)
      genotypes in Cordoba province, Argentina, over a 12-year period and to study the
      changes at the molecular level. The HCV genotype was determined in 357 HCV
      infected patients, and the phylogeny and demographic reconstruction for HCV-1 was
      assessed. A significant reduction in HCV-2 prevalence with respect to HCV-1 in
      Cordoba after 2003 was observed. These findings are consistent with the
      epidemiological changes observed in South America. Nevertheless, the consequences
      of these changes remain to be elucidated. 

PMID- 25762310
TI  - Inhibition of neutrophil collagenase/MMP-8 and gelatinase B/MMP-9 and protection
      against endotoxin shock.
AB  - Endotoxin shock is a life-threatening disorder, associated with the rapid release
      of neutrophil enzymes, including neutrophil collagenase/matrix metalloproteinase
      8 (MMP-8) and gelatinase B/matrix metalloproteinase-9 (MMP-9). After activation,
      these enzymes cleave extracellular matrix components and cytokines and thus may
      contribute to shock syndrome development. MMP inhibitors have been suggested as
      immunotherapy of endotoxin shock. However, little is known about the therapeutic
      time window of MMP inhibition. Here, a sublethal endotoxin shock mouse model was
      used to evaluate the effect of an MMP inhibiting peptide (P2) after intravenous
      or intraperitoneal injection and to study the time window between LPS and
      inhibitor injections. With the use of a specific ELISA the plasma P2
      concentrations were monitored. Whereas we corroborated the treatment strategy of
      MMP targeting in endotoxin shock with a new inhibitor, we also demonstrated that
      the time window, within which effective MMP inhibition increased the survival
      rates, is rather limited. 

PMID- 25762311
TI  - Starting from the ground state up: factors influencing synaptic plasticity.

PMID- 25762312
TI  - A method to quantify FRET stoichiometry with phasor plot analysis and acceptor
      lifetime ingrowth.
AB  - FRET is widely used for the study of protein-protein interactions in biological
      samples. However, it is difficult to quantify both the FRET efficiency (E) and
      the affinity (Kd) of the molecular interaction from intermolecular FRET signals
      in samples of unknown stoichiometry. Here, we present a method for the
      simultaneous quantification of the complete set of interaction parameters,
      including fractions of bound donors and acceptors, local protein concentrations,
      and dissociation constants, in each image pixel. The method makes use of
      fluorescence lifetime information from both donor and acceptor molecules and
      takes advantage of the linear properties of the phasor plot approach. We
      demonstrate the capability of our method in vitro in a microfluidic device and
      also in cells, via the determination of the binding affinity between tagged
      versions of glutathione and glutathione S-transferase, and via the determination
      of competitor concentration. The potential of the method is explored with
      simulations. 

PMID- 25762313
TI  - Calcium-Induced calcium release during action potential firing in developing
      inner hair cells.
AB  - In the mature auditory system, inner hair cells (IHCs) convert sound-induced
      vibrations into electrical signals that are relayed to the central nervous system
      via auditory afferents. Before the cochlea can respond to normal sound levels,
      developing IHCs fire calcium-based action potentials that disappear close to the
      onset of hearing. Action potential firing triggers transmitter release from the
      immature IHC that in turn generates experience-independent firing in auditory
      neurons. These early signaling events are thought to be essential for the
      organization and development of the auditory system and hair cells. A critical
      component of the action potential is the rise in intracellular calcium that
      activates both small conductance potassium channels essential during membrane
      repolarization, and triggers transmitter release from the cell. Whether this
      calcium signal is generated by calcium influx or requires calcium-induced calcium
      release (CICR) is not yet known. IHCs can generate CICR, but to date its
      physiological role has remained unclear. Here, we used high and low
      concentrations of ryanodine to block or enhance CICR to determine whether calcium
      release from intracellular stores affected action potential waveform, interspike
      interval, or changes in membrane capacitance during development of mouse IHCs.
      Blocking CICR resulted in mixed action potential waveforms with both brief and
      prolonged oscillations in membrane potential and intracellular calcium. This
      mixed behavior is captured well by our mathematical model of IHC electrical
      activity. We perform two-parameter bifurcation analysis of the model that
      predicts the dependence of IHCs firing patterns on the level of activation of two
      parameters, the SK2 channels activation and CICR rate. Our data show that CICR
      forms an important component of the calcium signal that shapes action potentials
      and regulates firing patterns, but is not involved directly in triggering
      exocytosis. These data provide important insights into the calcium signaling
      mechanisms involved in early developmental processes. 

PMID- 25762314
TI  - Effect of phosphorylation on EGFR dimer stability probed by single-molecule
      dynamics and FRET/FLIM.
AB  - Deregulation of epidermal growth factor receptor (EGFR) signaling has been
      correlated with the development of a variety of human carcinomas. EGF-induced
      receptor dimerization and consequent trans- auto-phosphorylation are among the
      earliest events in signal transduction. Binding of EGF is thought to induce a
      conformational change that consequently unfolds an ectodomain loop required for
      dimerization indirectly. It may also induce important allosteric changes in the
      cytoplasmic domain. Despite extensive knowledge on the physiological activation
      of EGFR, the effect of targeted therapies on receptor conformation is not known
      and this particular aspect of receptor function, which can potentially be
      influenced by drug treatment, may in part explain the heterogeneous clinical
      response among cancer patients. Here, we used Forster resonance energy
      transfer/fluorescence lifetime imaging microscopy (FRET/FLIM) combined with two
      color single-molecule tracking to study the effect of ATP-competitive small
      molecule tyrosine kinase inhibitors (TKIs) and phosphatase-based manipulation of
      EGFR phosphorylation on live cells. The distribution of dimer on-times was fitted
      to a monoexponential to extract dimer off-rates (koff). Our data show that
      pretreatment with gefitinib (active conformation binder) stabilizes the EGFR
      ligand-bound homodimer. Overexpression of EGFR-specific DEP-1 phosphatase was
      also found to have a stabilizing effect on the homodimer. No significant
      difference in the koff of the dimer could be detected when an anti-EGFR antibody
      (425 Snap single-chain variable fragment) that allows for dimerization of ligand
      bound receptors, but not phosphorylation, was used. These results suggest that
      both the conformation of the extracellular domain and phosphorylation status of
      the receptor are involved in modulating the stability of the dimer. The relative
      fractions of these two EGFR subpopulations (interacting versus free) were
      obtained by a fractional-intensity analysis of ensemble FRET/FLIM images. Our
      combined imaging approach showed that both the fraction and affinity (surrogate
      of conformation at a single-molecule level) increased after gefitinib
      pretreatment or DEP-1 phosphatase overexpression. Using an EGFR mutation (I706Q,
      V948R) that perturbs the ability of EGFR to dimerize intracellularly, we showed
      that a modest drug-induced increase in the fraction/stability of the EGFR
      homodimer may have a significant biological impact on the tumor cell's
      proliferation potential. 

PMID- 25762315
TI  - Measurement of subcellular force generation in neurons.
AB  - Forces are important for neuronal outgrowth during the initial wiring of the
      nervous system and after trauma, yet subcellular force generation over the
      microtubule-rich region at the rear of the growth cone and along the axon has
      never, to our knowledge, been directly measured. Because previous studies have
      indicated microtubule polymerization and the microtubule-associated proteins
      Kinesin-1 and dynein all generate forces that push microtubules forward, a major
      question is whether the net forces in these regions are contractile or expansive.
      A challenge in addressing this is that measuring local subcellular force
      generation is difficult. Here we develop an analytical mathematical model that
      describes the relationship between unequal subcellular forces arranged in series
      within the neuron and the net overall tension measured externally. Using force
      calibrated towing needles to measure and apply forces, in combination with docked
      mitochondria to monitor subcellular strain, we then directly measure force
      generation over the rear of the growth cone and along the axon of chick sensory
      neurons. We find the rear of the growth cone generates 2.0 nN of contractile
      force, the axon generates 0.6 nN of contractile force, and that the net overall
      tension generated by the neuron is 1.3 nN. This work suggests that the forward
      bulk flow of the cytoskeletal framework that occurs during axonal elongation and
      growth-cone pauses arises because strong contractile forces in the rear of the
      growth cone pull material forward. 

PMID- 25762316
TI  - Effect of the initial synaptic state on the probability to induce long-term
      potentiation and depression.
AB  - Long-term potentiation (LTP) and long-term depression (LTD) are the two major
      forms of long-lasting synaptic plasticity in the mammalian neurons, and are
      directly related to higher brain functions such as learning and memory.
      Experimentally, they are characterized by a change in the strength of a synaptic
      connection induced by repetitive and properly patterned stimulation protocols.
      Although many important details of the molecular events leading to LTP and LTD
      are known, experimenters often report problems in using standard induction
      protocols to obtain consistent results, especially for LTD in vivo. We
      hypothesize that a possible source of confusion in interpreting the results, from
      any given experiment on synaptic plasticity, can be the intrinsic limitation of
      the experimental techniques, which cannot take into account the actual state and
      peak conductance of the synapses before the conditioning protocol. In this
      article, we investigate the possibility that the same experimental protocol may
      result in different consequences (e.g., LTD instead of LTP), according to the
      initial conditions of the stimulated synapses, and can generate confusing
      results. Using biophysical models of synaptic plasticity and hippocampal CA1
      pyramidal neurons, we study how, why, and to what extent the phenomena observed
      at the soma after induction of LTP/LTD reflects the actual (local) synaptic
      state. The model and the results suggest a physiologically plausible explanation
      for why LTD induction is experimentally difficult to obtain. They also suggest
      experimentally testable predictions on the stimulation protocols that may be more
      effective.

PMID- 25762317
TI  - The role of exciton delocalization in the major photosynthetic light-harvesting
      antenna of plants.
AB  - In the major peripheral plant light-harvesting complex LHCII, excitation energy
      is transferred between chlorophylls along an energetic cascade before it is
      transmitted further into the photosynthetic assembly to be converted into
      chemical energy. The efficiency of these energy transfer processes involves a
      complicated interplay of pigment-protein structural reorganization and protein
      dynamic disorder, and the system must stay robust within the fluctuating protein
      environment. The final, lowest energy site has been proposed to exist within a
      trimeric excitonically coupled chlorophyll (Chl) cluster, comprising Chls a610
      a611-a612. We studied an LHCII monomer with a site-specific mutation resulting in
      the loss of Chls a611and a612, and find that this mutant exhibits two predominant
      overlapping fluorescence bands. From a combination of bulk measurements, single
      molecule fluorescence characterization, and modeling, we propose the two
      fluorescence bands originate from differing conditions of exciton delocalization
      and localization realized in the mutant. Disruption of the excitonically coupled
      terminal emitter Chl trimer results in an increased sensitivity of the excited
      state energy landscape to the disorder induced by the protein conformations.
      Consequently, the mutant demonstrates a loss of energy transfer efficiency. On
      the contrary, in the wild-type complex, the strong resonance coupling and
      correspondingly high degree of excitation delocalization within the Chls a610
      a611-a612 cluster dampens the influence of the environment and ensures optimal
      communication with neighboring pigments. These results indicate that the terminal
      emitter trimer is thus an essential design principle for maintaining the
      efficient light-harvesting function of LHCII in the presence of protein disorder.

PMID- 25762318
TI  - C-fiber recovery cycle supernormality depends on ion concentration and ion
      channel permeability.
AB  - Following each action potential, C-fiber nociceptors undergo cyclical changes in
      excitability, including a period of superexcitability, before recovering their
      basal excitability state. The increase in superexcitability during this recovery
      cycle depends upon their immediate firing history of the axon, but also
      determines the instantaneous firing frequency that encodes pain intensity. To
      explore the mechanistic underpinnings of the recovery cycle phenomenon a
      biophysical model of a C-fiber has been developed. The model represents the
      spatial extent of the axon including its passive properties as well as ion
      channels and the Na/K-ATPase ion pump. Ionic concentrations were represented
      inside and outside the membrane. The model was able to replicate the typical
      transitions in excitability from subnormal to supernormal observed empirically
      following a conducted action potential. In the model, supernormality depended on
      the degree of conduction slowing which in turn depends upon the frequency of
      stimulation, in accordance with experimental findings. In particular, we show
      that activity-dependent conduction slowing is produced by the accumulation of
      intraaxonal sodium. We further show that the supernormal phase results from a
      reduced potassium current Kdr as a result of accumulation of periaxonal potassium
      in concert with a reduced influx of sodium through Nav1.7 relative to Nav1.8
      current. This theoretical prediction was supported by data from an in vitro
      preparation of small rat dorsal root ganglion somata showing a reduction in the
      magnitude of tetrodotoxin-sensitive relative to tetrodotoxin -resistant whole
      cell current. Furthermore, our studies provide support for the role of
      depolarization in supernormality, as previously suggested, but we suggest that
      the basic mechanism depends on changes in ionic concentrations inside and outside
      the axon. The understanding of the mechanisms underlying repetitive discharges in
      recovery cycles may provide insight into mechanisms of spontaneous activity,
      which recently has been shown to correlate to a perceived level of pain. 

PMID- 25762319
TI  - Physiological and pharmacological modulation of the embryonic skeletal muscle
      calcium channel splice variant CaV1.1e.
AB  - CaV1.1e is the voltage-gated calcium channel splice variant of embryonic skeletal
      muscle. It differs from the adult CaV1.1a splice variant by the exclusion of exon
      29 coding for 19 amino acids in the extracellular loop connecting transmembrane
      domains IVS3 and IVS4. Like the adult splice variant CaV1.1a, the embryonic
      CaV1.1e variant functions as voltage sensor in excitation-contraction coupling,
      but unlike CaV1.1a it also conducts sizable calcium currents. Consequently,
      physiological or pharmacological modulation of calcium currents may have a
      greater impact in CaV1.1e expressing muscle cells. Here, we analyzed the effects
      of L-type current modulators on whole-cell current properties in dysgenic (CaV1.1
      null) myotubes reconstituted with either CaV1.1a or CaV1.1e. Furthermore, we
      examined the physiological current modulation by interactions with the ryanodine
      receptor using a chimeric CaV1.1e construct in which the cytoplasmic II-III loop,
      essential for skeletal muscle excitation-contraction coupling, has been replaced
      with the corresponding but nonfunctional loop from the Musca channel. Whereas the
      equivalent substitution in CaV1.1a had abolished the calcium currents,
      substitution of the II-III loop in CaV1.1e did not significantly reduce current
      amplitudes. This indicates that CaV1.1e is not subject to retrograde coupling
      with the ryanodine receptor and that the retrograde coupling mechanism in CaV1.1a
      operates by counteracting the limiting effects of exon 29 inclusion on the
      current amplitude. Pharmacologically, CaV1.1e behaves like other L-type calcium
      channels. Its currents are substantially increased by the calcium channel agonist
      Bay K 8644 and inhibited by the calcium channel blocker nifedipine in a dose
      dependent manner. With an IC50 of 0.37 MUM for current inhibition by nifedipine,
      CaV1.1e is a potential drug target for the treatment of myotonic dystrophy. It
      might block the excessive calcium influx resulting from the aberrant expression
      of the embryonic splice variant CaV1.1e in the skeletal muscles of myotonic
      dystrophy patients. 

PMID- 25762320
TI  - Exploring the mechanism of general anesthesia: kinetic analysis of GABAA receptor
      electrophysiology.
AB  - A kinetic model of the effect of agonist and anesthetics on ligand-gated ion
      channels, developed in earlier work, is further refined and used to predict
      traces observed in fast-perfusion electrophysiological studies on recombinant
      GABAA receptors under a wide range of agonist and/or anesthetic concentrations.
      The model incorporates only three conformational states (resting, open, and
      desensitized) but allows for the modulation of the conformational free energy
      landscape connecting these states resulting from adsorption of agonist and/or
      anesthetic to the bilayer in which the protein is embedded. The model is shown to
      reproduce the diverse and complex features of experimental traces remarkably
      well, including both anesthetic-induced and agonist-induced traces, as well as
      the modulation of agonist-induced traces by anesthetic, either coapplied or
      continuously present. The solutions to the kinetic equations, which give the time
      dependence of each of the nine protein states (three ligation states for each of
      the three conformations), describe the flow of probability among these states and
      thus reveal the kinetic underpinnings of the traces. Many of the parameters in
      the model, such as the desorption rate constants of anesthetic and agonist, are
      directly related to model-independent experimental measurements and thus can
      serve as a definitive test of its validity. 

PMID- 25762321
TI  - Computational and functional analyses of a small-molecule binding site in ROMK.
AB  - The renal outer medullary potassium channel (ROMK, or Kir1.1, encoded by KCNJ1)
      critically regulates renal tubule electrolyte and water transport and hence blood
      volume and pressure. The discovery of loss-of-function mutations in KCNJ1
      underlying renal salt and water wasting and lower blood pressure has sparked
      interest in developing new classes of antihypertensive diuretics targeting ROMK.
      The recent development of nanomolar-affinity small-molecule inhibitors of ROMK
      creates opportunities for exploring the chemical and physical basis of ligand
      channel interactions required for selective ROMK inhibition. We previously
      reported that the bis-nitro-phenyl ROMK inhibitor VU591 exhibits voltage
      dependent knock-off at hyperpolarizing potentials, suggesting that the binding
      site is located within the ion-conduction pore. In this study, comparative
      molecular modeling and in silico ligand docking were used to interrogate the full
      length ROMK pore for energetically favorable VU591 binding sites. Cluster
      analysis of 2498 low-energy poses resulting from 9900 Monte Carlo docking
      trajectories on each of 10 conformationally distinct ROMK comparative homology
      models identified two putative binding sites in the transmembrane pore that were
      subsequently tested for a role in VU591-dependent inhibition using site-directed
      mutagenesis and patch-clamp electrophysiology. Introduction of mutations into the
      lower site had no effect on the sensitivity of the channel to VU591. In contrast,
      mutations of Val(168) or Asn(171) in the upper site, which are unique to ROMK
      within the Kir channel family, led to a dramatic reduction in VU591 sensitivity.
      This study highlights the utility of computational modeling for defining ligand
      ROMK interactions and proposes a mechanism for inhibition of ROMK.

PMID- 25762322
TI  - Cytoskeletal pinning controls phase separation in multicomponent lipid membranes.
AB  - We study the effect of a minimal cytoskeletal network formed on the surface of
      giant unilamellar vesicles by the prokaryotic tubulin homolog, FtsZ, on phase
      separation in freestanding lipid membranes. FtsZ has been modified to interact
      with the membrane through a membrane targeting sequence from the prokaryotic
      protein MinD. FtsZ with the attached membrane targeting sequence efficiently
      forms a highly interconnected network on membranes with a concentration-dependent
      mesh size, much similar to the eukaryotic cytoskeletal network underlying the
      plasma membrane. Using giant unilamellar vesicles formed from a quaternary lipid
      mixture, we demonstrate that the artificial membrane-associated cytoskeleton, on
      the one hand, suppresses large-scale phase separation below the phase transition
      temperature, and, on the other hand, preserves phase separation above the
      transition temperature. Our experimental observations support the ideas put
      forward in our previous simulation study: In particular, the picket fence effect
      on phase separation may explain why micrometer-scale membrane domains are
      observed in isolated, cytoskeleton-free giant plasma membrane vesicles, but not
      in intact cell membranes. The experimentally observed suppression of large-scale
      phase separation much below the transition temperatures also serves as an
      argument in favor of the cryoprotective role of the cytoskeleton. 

PMID- 25762323
TI  - The lantibiotic nisin induces lipid II aggregation, causing membrane instability
      and vesicle budding.
AB  - The antimicrobial peptide nisin exerts its activity by a unique dual mechanism.
      It permeates the cell membranes of Gram-positive bacteria by binding to the cell
      wall precursor Lipid II and inhibits cell wall synthesis. Binding of nisin to
      Lipid II induces the formation of large nisin-Lipid II aggregates in the membrane
      of bacteria as well as in Lipid II-doped model membranes. Mechanistic details of
      the aggregation process and its impact on membrane permeation are still
      unresolved. In our experiments, we found that fluorescently labeled nisin bound
      very inhomogeneously to bacterial membranes as a consequence of the strong
      aggregation due to Lipid II binding. A correlation between cell membrane damage
      and nisin aggregation was observed in vivo. To further investigate the
      aggregation process of Lipid II and nisin, we assessed its dynamics by single
      molecule microscopy of fluorescently labeled Lipid II molecules in giant
      unilamellar vesicles using light-sheet illumination. We observed a continuous
      reduction of Lipid II mobility due to a steady growth of nisin-Lipid II
      aggregates as a function of time and nisin concentration. From the measured
      diffusion constants of Lipid II, we estimated that the largest aggregates
      contained tens of thousands of Lipid II molecules. Furthermore, we observed that
      the formation of large nisin-Lipid II aggregates induced vesicle budding in giant
      unilamellar vesicles. Thus, we propose a membrane permeation mechanism that is
      dependent on the continuous growth of nisin-Lipid II aggregation and probably
      involves curvature effects on the membrane.

PMID- 25762324
TI  - Rhodopsin/lipid hydrophobic matching-rhodopsin oligomerization and function.
AB  - Lipid composition of the membrane and rhodopsin packing density strongly modulate
      the early steps of the visual response of photoreceptor membranes. In this study,
      lipid-order and bovine rhodopsin function in proteoliposomes composed of the sn-1
      chain perdeuterated lipids 14:0d27-14:1-PC, 16:0d31-16:1-PC, 18:0d35-18:1-PC, or
      20:0d39-20:1-PC at rhodopsin/lipid molar ratios from 1:70 to 1:1000 (mol/mol)
      were investigated. Clear evidence for matching of hydrophobic regions on
      rhodopsin transmembrane helices and hydrophobic thickness of lipid bilayers was
      observed from (2)H nuclear magnetic resonance order parameter measurements at low
      rhodopsin concentrations. Thin bilayers stretched to match the length of
      transmembrane helices observed as increase of sn-1 chain order, while thicker
      bilayers were compressed near the protein. A quantitative analysis of lipid-order
      parameter changes suggested that the protein adjusts its conformation to bilayer
      hydrophobic thickness as well, which confirmed our earlier circular-dichroism
      measurements. Changes in lipid order parameters upon rhodopsin incorporation
      vanished for bilayers with a hydrophobic thickness of 27 +/- 1 A, suggesting that
      this is the bilayer thickness at which rhodopsin packs in bilayers at the lowest
      membrane perturbation. The lipid-order parameter studies also indicated that a
      hydrophobic mismatch between rhodopsin and lipids triggers rhodopsin
      oligomerization with increasing rhodopsin concentrations. Both hydrophobic
      mismatch and rhodopsin oligomerization result in substantial shifts of the
      equilibrium between the photointermediates metarhodopsin I and metarhodopsin II;
      increasing bilayer thickness favors formation of metarhodopsin II while
      oligomerization favors metarhodopsin I. The results highlight the importance of
      hydrophobic matching for rhodopsin structure, oligomerization, and function.

PMID- 25762325
TI  - Influence of fluorescent tag on the motility properties of kinesin-1 in single
      molecule assays.
AB  - Molecular motors such as kinesin and dynein use the energy derived from ATP
      hydrolysis to walk processively along microtubule tracks and transport various
      cargoes inside the cell. Recent advancements in fluorescent protein (FP) research
      enable motors to be fluorescently labeled such that single molecules can be
      visualized inside cells in multiple colors. The performance of these fluorescent
      tags can vary depending on their spectral properties and a natural tendency for
      oligomerization. Here we present a survey of different fluorescent tags fused to
      kinesin-1 and studied by single-molecule motility assays of mammalian cell
      lysates. We tested eight different FP tags and found that seven of them display
      sufficient fluorescence intensity and photostability to visualize motility
      events. Although none of the FP tags interfere with the enzymatic properties of
      the motor, four of the tags (EGFP, monomeric EGFP, tagRFPt, and mApple) cause
      aberrantly long motor run lengths. This behavior is unlikely to be due to
      electrostatic interactions and is probably caused by tag-dependent
      oligomerization events that appear to be facilitated by fusion to the dimeric
      kinesin-1. We also compared the single-molecule performance of various
      fluorescent SNAP and HALO ligands. We found that although both green and red SNAP
      ligands provide sufficient fluorescent signal, only the tetramethyl rhodamine
      (TMR) HALO ligand provides sufficient signal for detection in these assays. This
      study will serve as a valuable reference for choosing fluorescent labels for
      single-molecule motility assays. 

PMID- 25762326
TI  - Torque transmission mechanism via DELSEED loop of F1-ATPase.
AB  - F1-ATPase (F1) is an ATP-driven rotary motor in which the three catalytic beta
      subunits in the stator ring sequentially induce the unidirectional rotation of
      the rotary gamma subunit. Many lines of evidence have revealed open-to-closed
      conformational transitions in the beta subunit that swing the C-terminal domain
      inward. This conformational transition causes a C-terminal protruding loop with
      conserved sequence DELSEED to push the gamma subunit. Previous work, where all
      residues of DELSEED were substituted with glycine to disrupt the specific
      interaction with gamma and introduce conformational flexibility, showed that F1
      still rotated, but that the torque was halved, indicating a remarkable impact on
      torque transmission. In this study, we conducted a stall-and-release experiment
      on F1 with a glycine-substituted DELSEED loop to investigate the impact of the
      glycine substitution on torque transmission upon ATP binding and ATP hydrolysis.
      The mutant F1 showed a significantly reduced angle-dependent change in ATP
      affinity, whereas there was no change in the equilibrium for ATP hydrolysis.
      These findings indicate that the DELSEED loop is predominantly responsible for
      torque transmission upon ATP binding but not for that upon ATP hydrolysis. 

PMID- 25762328
TI  - Bayesian inference of initial models in cryo-electron microscopy using pseudo
      atoms.
AB  - Single-particle cryo-electron microscopy is widely used to study the structure of
      macromolecular assemblies. Tens of thousands of noisy two-dimensional images of
      the macromolecular assembly viewed from different directions are used to infer
      its three-dimensional structure. The first step is to estimate a low-resolution
      initial model and initial image orientations. This is a challenging global
      optimization problem with many unknowns, including an unknown orientation for
      each two-dimensional image. Obtaining a good initial model is crucial for the
      success of the subsequent refinement step. We introduce a probabilistic algorithm
      for estimating an initial model. The algorithm is fast, has very few algorithmic
      parameters, and yields information about the precision of estimated model
      parameters in addition to the parameters themselves. Our algorithm uses a pseudo
      atomic model to represent the low-resolution three-dimensional structure, with
      isotropic Gaussian components as moveable pseudo-atoms. This leads to a
      significant reduction in the number of parameters needed to represent the three
      dimensional structure, and a simplified way of computing two-dimensional
      projections. It also contributes to the speed of the algorithm. We combine the
      estimation of the unknown three-dimensional structure and image orientations in a
      Bayesian framework. This ensures that there are very few parameters to set, and
      specifies how to combine different types of prior information about the structure
      with the given data in a systematic way. To estimate the model parameters we use
      Markov chain Monte Carlo sampling. The advantage is that instead of just
      obtaining point estimates of model parameters, we obtain an ensemble of models
      revealing the precision of the estimated parameters. We demonstrate the algorithm
      on both simulated and real data. 

PMID- 25762327
TI  - Speed of conformational change: comparing explicit and implicit solvent molecular
      dynamics simulations.
AB  - Adequate sampling of conformation space remains challenging in atomistic
      simulations, especially if the solvent is treated explicitly. Implicit-solvent
      simulations can speed up conformational sampling significantly. We compare the
      speed of conformational sampling between two commonly used methods of each class:
      the explicit-solvent particle mesh Ewald (PME) with TIP3P water model and a
      popular generalized Born (GB) implicit-solvent model, as implemented in the AMBER
      package. We systematically investigate small (dihedral angle flips in a protein),
      large (nucleosome tail collapse and DNA unwrapping), and mixed (folding of a
      miniprotein) conformational changes, with nominal simulation times ranging from
      nanoseconds to microseconds depending on system size. The speedups in
      conformational sampling for GB relative to PME simulations, are highly system-
      and problem-dependent. Where the simulation temperatures for PME and GB are the
      same, the corresponding speedups are approximately onefold (small conformational
      changes), between ~1- and ~100-fold (large changes), and approximately sevenfold
      (mixed case). The effects of temperature on speedup and free-energy landscapes,
      which may differ substantially between the solvent models, are discussed in
      detail for the case of miniprotein folding. In addition to speeding up
      conformational sampling, due to algorithmic differences, the implicit solvent
      model can be computationally faster for small systems or slower for large
      systems, depending on the number of solute and solvent atoms. For the
      conformational changes considered here, the combined speedups are approximately
      twofold, ~1- to 60-fold, and ~50-fold, respectively, in the low solvent viscosity
      regime afforded by the implicit solvent. For all the systems studied, 1)
      conformational sampling speedup increases as Langevin collision frequency
      (effective viscosity) decreases; and 2) conformational sampling speedup is mainly
      due to reduction in solvent viscosity rather than possible differences in free
      energy landscapes between the solvent models.

PMID- 25762329
TI  - Nucleation of polymorphic amyloid fibrils.
AB  - One and the same protein can self-assemble into amyloid fibrils with different
      morphologies. The phenomenon of fibril polymorphism is relevant biologically
      because different fibril polymorphs can have different toxicity, but there is no
      tool for predicting which polymorph forms and under what conditions. Here, we
      consider the nucleation of polymorphic amyloid fibrils occurring by direct
      polymerization of monomeric proteins into fibrils. We treat this process within
      the framework of our newly developed nonstandard nucleation theory, which allows
      prediction of the concentration dependence of the nucleation rate for different
      fibril polymorphs. The results highlight that the concentration dependence of the
      nucleation rate is closely linked with the protein solubility and a threshold
      monomer concentration below which fibril formation becomes biologically
      irrelevant. The relation between the nucleation rate, the fibril solubility, the
      threshold concentration, and the binding energies of the fibril building blocks
      within fibrils might prove a valuable tool for designing new experiments to
      control the formation of particular fibril polymorphs. 

PMID- 25762330
TI  - Probing the Huntingtin 1-17 membrane anchor on a phospholipid bilayer by using
      all-atom simulations.
AB  - Mislocalization and aggregation of the huntingtin protein are related to
      Huntington's disease. Its first exon-more specifically the first 17 amino acids
      (Htt17)-is crucial for the physiological and pathological functions of
      huntingtin. It regulates huntingtin's activity through posttranslational
      modifications and serves as an anchor to membrane-containing organelles of the
      cell. Recently, structure and orientation of the Htt17 membrane anchor were
      determined using a combined solution and solid-state NMR approach. This prompted
      us to refine this model by investigating the dynamics and thermodynamics of this
      membrane anchor on a POPC bilayer using all-atom, explicit solvent molecular
      dynamics and Hamiltonian replica exchange. Our simulations are combined with
      various experimental measurements to generate a high-resolution atomistic model
      for the huntingtin Htt17 membrane anchor on a POPC bilayer. More precisely, we
      observe that the single alpha-helix structure is more stable in the phospholipid
      membrane than the NMR model obtained in the presence of dodecylphosphocholine
      detergent micelles. The resulting Htt17 monomer has its hydrophobic plane
      oriented parallel to the bilayer surface. Our results further unveil the key
      residues interacting with the membrane in terms of hydrogen bonds, salt-bridges,
      and nonpolar contributions. We also observe that Htt17 equilibrates at a well
      defined insertion depth and that it perturbs the physical properties-order
      parameter, thickness, and area per lipid-of the bilayer in a manner that could
      favor its dimerization. Overall, our observations reinforce and refine the NMR
      measurements on the Htt17 membrane anchor segment of huntingtin that is of
      fundamental importance to its biological functions.

PMID- 25762331
TI  - Arresting amyloid with coulomb's law: acetylation of ALS-linked SOD1 by aspirin
      impedes aggregation.
AB  - Although the magnitude of a protein's net charge (Z) can control its rate of self
      assembly into amyloid, and its interactions with cellular membranes, the net
      charge of a protein is not viewed as a druggable parameter. This article
      demonstrates that aspirin (the quintessential acylating pharmacon) can inhibit
      the amyloidogenesis of superoxide dismutase (SOD1) by increasing the intrinsic
      net negative charge of the polypeptide, i.e., by acetylation (neutralization) of
      multiple lysines. The protective effects of acetylation were diminished (but not
      abolished) in 100 mM NaCl and were statistically significant: a total of 432
      thioflavin-T amyloid assays were performed for all studied proteins. The
      acetylation of as few as three lysines by aspirin in A4V apo-SOD1-a variant that
      causes familial amyotrophic lateral sclerosis (ALS)-delayed amyloid nucleation by
      38% and slowed amyloid propagation by twofold. Lysines in wild-type- and ALS
      variant apo-SOD1 could also be peracetylated with aspirin after fibrillization,
      resulting in supercharged fibrils, with increases in formal net charge of ~2
      million units. Peracetylated SOD1 amyloid defibrillized at temperatures below
      unacetylated fibrils, and below the melting temperature of native Cu2,Zn2-SOD1
      (e.g., fibril Tm = 84.49 degrees C for acetylated D90A apo-SOD1 fibrils).
      Targeting the net charge of native or misfolded proteins with small molecules
      analogous to how an enzyme's Km or Vmax are medicinally targeted-holds promise as
      a strategy in the design of therapies for diseases linked to protein self
      assembly.

PMID- 25762332
TI  - Room-temperature distance measurements of immobilized spin-labeled protein by
      DEER/PELDOR.
AB  - Nitroxide spin labels are used for double electron-electron resonance (DEER)
      measurements of distances between sites in biomolecules. Rotation of gem
      dimethyls in commonly used nitroxides causes spin echo dephasing times (Tm) to be
      too short to perform DEER measurements at temperatures between ~80 and 295 K,
      even in immobilized samples. A spirocyclohexyl spin label has been prepared that
      has longer Tm between 80 and 295 K in immobilized samples than conventional
      labels. Two of the spirocyclohexyl labels were attached to sites on T4 lysozyme
      introduced by site-directed spin labeling. Interspin distances up to ~4 nm were
      measured by DEER at temperatures up to 160 K in water/glycerol glasses. In a
      glassy trehalose matrix the Tm for the doubly labeled T4 lysozyme was long enough
      to measure an interspin distance of 3.2 nm at 295 K, which could not be measured
      for the same protein labeled with the conventional 1-oxyl-2,2,5,5-tetramethyl-3
      pyrroline-3-(methyl)methanethio-sulfonate label.

PMID- 25762333
TI  - Crowding induces complex ergodic diffusion and dynamic elongation of large DNA
      molecules.
AB  - Despite the ubiquity of molecular crowding in living cells, the effects of
      crowding on the dynamics of genome-sized DNA are poorly understood. Here, we
      track single, fluorescent-labeled large DNA molecules (11, 115 kbp) diffusing in
      dextran solutions that mimic intracellular crowding conditions (0-40%), and
      determine the effects of crowding on both DNA mobility and conformation. Both
      DNAs exhibit ergodic Brownian motion and comparable mobility reduction in all
      conditions; however, crowder size (10 vs. 500 kDa) plays a critical role in the
      underlying diffusive mechanisms and dependence on crowder concentration.
      Surprisingly, in 10-kDa dextran, crowder influence saturates at ~20% with an ~5*
      drop in DNA diffusion, in stark contrast to exponentially retarded mobility,
      coupled to weak anomalous subdiffusion, with increasing concentration of 500-kDa
      dextran. Both DNAs elongate into lower-entropy states (compared to random coil
      conformations) when crowded, with elongation states that are gamma distributed
      and fluctuate in time. However, the broadness of the distribution of states and
      the time-dependence and length scale of elongation length fluctuations depend on
      both DNA and crowder size with concentration having surprisingly little impact.
      Results collectively show that mobility reduction and coil elongation of large
      crowded DNAs are due to a complex interplay between entropic effects and crowder
      mobility. Although elongation and initial mobility retardation are driven by
      depletion interactions, subdiffusive dynamics, and the drastic exponential
      slowing of DNA, up to ~300*, arise from the reduced mobility of larger crowders.
      Our results elucidate the highly important and widely debated effects of cellular
      crowding on genome-sized DNA.

PMID- 25762334
TI  - Intramembrane proteolysis of beta-amyloid precursor protein by gamma-secretase is
      an unusually slow process.
AB  - Intramembrane proteolysis has emerged as a key mechanism required for membrane
      proteostasis and cellular signaling. One of the intramembrane-cleaving proteases
      (I-CLiPs), gamma-secretase, is also intimately implicated in Alzheimer's disease,
      a major neurodegenerative disease and leading cause of dementia. High-resolution
      crystal structural analyses have revealed that I-CLiPs harbor their active sites
      buried deeply in the membrane bilayer. Surprisingly, however, the key kinetic
      constants of these proteases, turnover number kcat and catalytic efficiency
      kcat/KM, are largely unknown. By investigating the kinetics of intramembrane
      cleavage of the Alzheimer's disease-associated beta-amyloid precursor protein in
      vitro and in human embryonic kidney cells, we show that gamma-secretase is a very
      slow protease with a kcat value similar to those determined recently for rhomboid
      type I-CLiPs. Our results indicate that low turnover numbers may be a general
      feature of I-CLiPs.

PMID- 25762335
TI  - Modelling toehold-mediated RNA strand displacement.
AB  - We study the thermodynamics and kinetics of an RNA toehold-mediated strand
      displacement reaction with a recently developed coarse-grained model of RNA.
      Strand displacement, during which a single strand displaces a different strand
      previously bound to a complementary substrate strand, is an essential mechanism
      in active nucleic acid nanotechnology and has also been hypothesized to occur in
      vivo. We study the rate of displacement reactions as a function of the length of
      the toehold and temperature and make two experimentally testable predictions:
      that the displacement is faster if the toehold is placed at the 5' end of the
      substrate; and that the displacement slows down with increasing temperature for
      longer toeholds.

PMID- 25762336
TI  - Rapid, high-throughput tracking of bacterial motility in 3D via phase-contrast
      holographic video microscopy.
AB  - Tracking fast-swimming bacteria in three dimensions can be extremely challenging
      with current optical techniques and a microscopic approach that can rapidly
      acquire volumetric information is required. Here, we introduce phase-contrast
      holographic video microscopy as a solution for the simultaneous tracking of
      multiple fast moving cells in three dimensions. This technique uses interference
      patterns formed between the scattered and the incident field to infer the three
      dimensional (3D) position and size of bacteria. Using this optical approach,
      motility dynamics of multiple bacteria in three dimensions, such as speed and
      turn angles, can be obtained within minutes. We demonstrated the feasibility of
      this method by effectively tracking multiple bacteria species, including
      Escherichia coli, Agrobacterium tumefaciens, and Pseudomonas aeruginosa. In
      addition, we combined our fast 3D imaging technique with a microfluidic device to
      present an example of a drug/chemical assay to study effects on bacterial
      motility. 

PMID- 25762337
TI  - Incorporating chromatin accessibility data into sequence-to-expression modeling.
AB  - Prediction of gene expression levels from regulatory sequences is one of the
      major challenges of genomic biology today. A particularly promising approach to
      this problem is that taken by thermodynamics-based models that interpret an
      enhancer sequence in a given cellular context specified by transcription factor
      concentration levels and predict precise expression levels driven by that
      enhancer. Such models have so far not accounted for the effect of chromatin
      accessibility on interactions between transcription factor and DNA and
      consequently on gene-expression levels. Here, we extend a thermodynamics-based
      model of gene expression, called GEMSTAT (Gene Expression Modeling Based on
      Statistical Thermodynamics), to incorporate chromatin accessibility data and
      quantify its effect on accuracy of expression prediction. In the new model,
      called GEMSTAT-A, accessibility at a binding site is assumed to affect the
      transcription factor's binding strength at the site, whereas all other aspects
      are identical to the GEMSTAT model. We show that this modification results in
      significantly better fits in a data set of over 30 enhancers regulating spatial
      expression patterns in the blastoderm-stage Drosophila embryo. It is important to
      note that the improved fits result not from an overall elevated accessibility in
      active enhancers but from the variation of accessibility levels within an
      enhancer. With whole-genome DNA accessibility measurements becoming increasingly
      popular, our work demonstrates how such data may be useful for sequence-to
      expression models. It also calls for future advances in modeling accessibility
      levels from sequence and the transregulatory context, so as to predict accurately
      the effect of cis and trans perturbations on gene expression. 

PMID- 25762338
TI  - Anisotropy of bullet-shaped magnetite nanoparticles in the magnetotactic bacteria
      Desulfovibrio magneticus sp. Strain RS-1.
AB  - Magnetotactic bacteria (MTB) build magnetic nanoparticles in chain configuration
      to generate a permanent dipole in their cells as a tool to sense the Earth's
      magnetic field for navigation toward favorable habitats. The majority of known
      MTB align their nanoparticles along the magnetic easy axes so that the directions
      of the uniaxial symmetry and of the magnetocrystalline anisotropy coincide.
      Desulfovibrio magneticus sp. strain RS-1 forms bullet-shaped magnetite
      nanoparticles aligned along their (100) magnetocrystalline hard axis, a
      configuration energetically unfavorable for formation of strong dipoles. We used
      ferromagnetic resonance spectroscopy to quantitatively determine the
      magnetocrystalline and uniaxial anisotropy fields of the magnetic assemblies as
      indicators for a cellular dipole with stable direction in strain RS-1.
      Experimental and simulated ferromagnetic resonance spectral data indicate that
      the negative effect of the configuration is balanced by the bullet-shaped
      morphology of the nanoparticles, which generates a pronounced uniaxial anisotropy
      field in each magnetosome. The quantitative comparison with anisotropy fields of
      Magnetospirillum gryphiswaldense, a model MTB with equidimensional magnetite
      particles aligned along their (111) magnetic easy axes in well-organized chain
      assemblies, shows that the effectiveness of the dipole is similar to that in RS
      1. From a physical perspective, this could be a reason for the persistency of
      bullet-shaped magnetosomes during the evolutionary development of magnetotaxis in
      MTB. 

PMID- 25762339
TI  - Switching of bacterial flagellar motors [corrected] triggered by mutant FliG.
AB  - Binding of the chemotaxis response regulator CheY-P promotes switching between
      rotational states in flagellar motors of the bacterium Escherichia coli. Here, we
      induced switching in the absence of CheY-P by introducing copies of a mutant FliG
      locked in the clockwise (CW) conformation (FliG(CW)). The composition of the
      mixed FliG ring was estimated via fluorescence imaging, and the probability of CW
      rotation (CWbias) was determined from the rotation of tethered cells. The results
      were interpreted in the framework of a 1D Ising model. The data could be fit by
      assuming that mutant subunits are more stable in the CW conformation than in the
      counterclockwise conformation. We found that CWbias varies depending on the
      spatial arrangement of the assembled subunits in the FliG ring. This offers a
      possible explanation for a previous observation of hysteresis in the switch
      function in analogous mixed FliM motors-in motors containing identical fractions
      of mutant FliM(CW) in otherwise wild-type motors, the CWbias differed depending
      on whether mutant subunits were expressed in strains with native motors or native
      subunits were expressed in strains with mutant motors. 

PMID- 25762340
TI  - Interbeat interval modulation in the sinoatrial node as a result of membrane
      current stochasticity-a theoretical and numerical study.
AB  - A single isolated sinoatrial pacemaker cell presents intrinsic interbeat interval
      (IBI) variability that is believed to result from the stochastic characteristics
      of the opening and closing processes of membrane ion channels. To our knowledge,
      a novel mathematical framework was developed in this work to address the effect
      of current fluctuations on the IBIs of sinoatrial pacemaker cells. Using
      statistical modeling and employing the Fokker-Planck formalism, our mathematical
      analysis suggests that increased stochastic current fluctuation variance linearly
      increases the slope of phase-4 depolarization, hence the rate of activations.
      Single-cell and two-dimensional computerized numerical modeling of the sinoatrial
      node was conducted to validate the theoretical predictions using established
      ionic kinetics of the rabbit pacemaker and atrial cells. Our models also provide,
      to our knowledge, a novel complementary or alternative explanation to recent
      experimental observations showing a strong reduction in the mean IBI of Cx30
      deficient mice in comparison to wild-types, not fully explicable by the effects
      of intercellular decoupling. 

PMID- 25762341
TI  - Fundamental constraints on the abundances of chemotaxis proteins.
AB  - Flagellated bacteria, such as Escherichia coli, perform directed motion in
      gradients of concentration of attractants and repellents in a process called
      chemotaxis. The E. coli chemotaxis signaling pathway is a model for signal
      transduction, but it has unique features. We demonstrate that the need for fast
      signaling necessitates high abundances of the proteins involved in this pathway.
      We show that further constraints on the abundances of chemotaxis proteins arise
      from the requirements of self-assembly both of flagellar motors and of
      chemoreceptor arrays. All these constraints are specific to chemotaxis, and
      published data confirm that chemotaxis proteins tend to be more highly expressed
      than their homologs in other pathways. Employing a chemotaxis pathway model, we
      show that the gain of the pathway at the level of the response regulator CheY
      increases with overall chemotaxis protein abundances. This may explain why, at
      least in one E. coli strain, the abundance of all chemotaxis proteins is higher
      in media with lower nutrient content. We also demonstrate that the E. coli
      chemotaxis pathway is particularly robust to abundance variations of the motor
      protein FliM.

PMID- 25762342
TI  - The end is in sight: targeting sensitization in hematopoietic cell
      transplantation.

PMID- 25762343
TI  - CD44 Isoform Status Predicts Response to Treatment with Anti-CD44 Antibody in
      Cancer Patients.
AB  - PURPOSE: CD44, a cell surface glycoprotein, plays important roles in the
      development, progression, and metastasis of various tumor types. The aim of this
      study was to investigate how the expression of CD44 isoforms influences the
      interaction with hyaluronic acid (HA) and how differential isoform expression
      impacts antitumoral responses in vivo to treatment with RG7356, a humanized anti
      CD44 antibody inhibiting CD44-HA interaction. EXPERIMENTAL DESIGN: CD44 isoform
      expression on various tumor cell lines was analyzed by RNASeq while data on
      patients with different tumor types were obtained from the publicly available
      TCGA RNASeq dataset as well as a phase I clinical study (NCT01358903). We
      analyzed the link between HA production and CD44 isoform expression as well as
      the consequences of blocking the CD44-mediated cell adhesion to HA using RG7356.
      The correlation between CD44 isoform expression and antitumor response to RG7356
      treatment was investigated in the corresponding murine xenograft in vivo models
      as well as in a subset of patients treated with RG7356 from a recently completed
      phase I clinical trial. RESULTS: CD44 isoform expression, in particular
      expression of CD44s, is associated with HA production and predicts response to
      treatment with RG7356 in tumor xenograft models. Furthermore, patient data
      suggest that CD44 isoform status is a potential predictive biomarker for clinical
      response to treatment with RG7356. CONCLUSIONS: We provide new insights into the
      close interplay between CD44 and HA and a potential biomarker to enrich patient
      responses to RG7356 in the clinic.

PMID- 25762344
TI  - BATF2 Deficiency Promotes Progression in Human Colorectal Cancer via Activation
      of HGF/MET Signaling: A Potential Rationale for Combining MET Inhibitors with
      IFNs.
AB  - PURPOSE: BATF2, a novel IFN-stimulated gene, inhibits tumor cell proliferation,
      invasion, and migration. The objectives of this study were to determine how BATF2
      expression is associated with colorectal cancer progression and patient outcome,
      to investigate how BATF2 overexpression inhibits hepatocyte growth factor
      (HGF)/MET signaling, and to elucidate the rationale for combining MET inhibitors
      with IFN. EXPERIMENTAL DESIGN: BATF2 expression in colorectal cancer tissues was
      determined and correlated with colorectal cancer patient prognosis. Cultured
      colorectal cancer cells were used to investigate the effects of BATF2
      overexpression on the malignant phenotype of colorectal cancer cells and HGF/MET
      signaling. Tumor xenograft models were used to validate the effects of BATF2 on
      colorectal cancer xenograft growth and assess the efficacy of the combination of
      MET inhibitors with IFNs in colorectal cancer. RESULTS: In colorectal cancer
      tissues, BATF2 was found to be significantly downregulated, and its expression
      negatively correlated with MET expression. Decreased BATF2 expression was
      associated with progression and shorter patient survival in colorectal cancer.
      BATF2 overexpression promoted apoptosis and inhibited proliferation, migration,
      and invasion in colorectal cancer cells, as well as dramatically blunted tumor
      xenograft growth. In addition, MET inhibitors in combination with IFNbeta
      produced synergistic cytotoxicity both in vitro and in vivo. CONCLUSIONS:
      Together, these novel findings suggest that BATF2, a tumor suppressor gene, is a
      potent negative regulator of HGF/MET signaling in colorectal cancer and may serve
      as a prognostic tumor marker. Furthermore, these results provide a rationale for
      combining MET inhibitors with IFNs in preclinical trials.

PMID- 25762345
TI  - Recent trends in control methods for bacterial wilt diseases caused by Ralstonia
      solanacearum.
AB  - Previous studies have described the development of control methods against
      bacterial wilt diseases caused by Ralstonia solanacearum. This review focused on
      recent advances in control measures, such as biological, physical, chemical,
      cultural, and integral measures, as well as biocontrol efficacy and suppression
      mechanisms. Biological control agents (BCAs) have been dominated by bacteria
      (90%) and fungi (10%). Avirulent strains of R. solanacearum, Pseudomonas spp.,
      Bacillus spp., and Streptomyces spp. are well-known BCAs. New or uncommon BCAs
      have also been identified such as Acinetobacter sp., Burkholderia sp., and
      Paenibacillus sp. Inoculation methods for BCAs affect biocontrol efficacy, such
      as pouring or drenching soil, dipping of roots, and seed coatings. The amendment
      of different organic matter, such as plant residue, animal waste, and simple
      organic compounds, have frequently been reported to suppress bacterial wilt
      diseases. The combined application of BCAs and their substrates was shown to more
      effectively suppress bacterial wilt in the tomato. Suppression mechanisms are
      typically attributed to the antibacterial metabolites produced by BCAs or those
      present in natural products; however, the number of studies related to host
      resistance to the pathogen is increasing. Enhanced/modified soil microbial
      communities are also indirectly involved in disease suppression. New promising
      types of control measures include biological soil disinfection using substrates
      that release volatile compounds. This review described recent advances in
      different control measures. We focused on the importance of integrated pest
      management (IPM) for bacterial wilt diseases. 

PMID- 25762346
TI  - Surgery is no better than a simple sling for displaced fracture of upper arm,
      study finds.

PMID- 25762347
TI  - The effect of direct and indirect monitoring on generosity among preschoolers.
AB  - The purpose of this study is to examine the effect of direct and indirect
      monitoring on generosity among five-year-old preschoolers and to reveal the
      primary motivation for their generosity. Forty-two preschoolers completed one
      shot dictator games in Condition 1 while being monitored by the experimenter (the
      direct monitoring condition). In Condition 2, an image of staring eyes was
      displayed on the computer monitor (the indirect monitoring condition). In
      Condition 3, the computer monitor showed a picture of flowers (the non-monitoring
      condition). The results showed that while there was no difference between the
      mean levels of allocation in the indirect and non-monitoring conditions, the mean
      level of allocation in the direct monitoring condition was significantly higher
      than in the non-monitoring condition. These results showed that five-year-old
      preschoolers concerned with being monitored by, and receiving direct responses
      from, others tend to be more generous. 

PMID- 25762348
TI  - Pathology of Sarcoidosis.
AB  - Pathologists are frequently involved in the diagnosis of sarcoidosis on
      conventional biopsies or examining bronchoalveolar lavage fluid and assisting
      bronchoscopists when performing bronchial or transbronchial biopsies or
      transbronchial needle aspiration (TBNA)/endobronchial ultrasound (EBUS)-guided
      biopsies of enlarged lymph nodes. Histology generally does not pose difficult
      tasks in the correct clinical and imaging scenario, but atypical forms of
      sarcoidosis exist, and in these cases, the diagnosis may become difficult. When
      faced with granulomas in the lung, the evaluation of their qualitative features,
      anatomic distribution, and accompanying findings usually allows the pathologist
      to narrow considerably the differential diagnosis. The final diagnosis always
      requires the careful integration of the histology with the clinical, laboratory,
      and radiologic findings. How robust is the histologic component of the diagnosis
      varies from case to case, and the pathologist should always clearly discuss this
      point with the clinician; in general, the weaker the histology is, the stronger
      should be the clinical-radiologic findings, and vice versa. The differential
      diagnosis of sarcoidosis includes granulomatous infections, hypersensitivity
      pneumonitis, pneumoconiosis, autoimmune diseases (e.g., inflammatory bowel
      disease, primary biliary cirrhosis, several collagen vascular diseases
      (particularly Sjogren), drug reactions, chronic aspiration, and even diffuse
      fibrosing diseases. In this review, conventional and unusual histologic findings
      of pulmonary sarcoidosis are presented, highlighting the role of the pathologist
      and discussing the main differential diagnoses. 

PMID- 25762350
TI  - Visualization of nanocrystal breathing modes at extreme strains.
AB  - Nanoscale dimensions in materials lead to unique electronic and structural
      properties with applications ranging from site-specific drug delivery to anodes
      for lithium-ion batteries. These functional properties often involve large
      amplitude strains and structural modifications, and thus require an understanding
      of the dynamics of these processes. Here we use femtosecond X-ray scattering
      techniques to visualize, in real time and with atomic-scale resolution, light
      induced anisotropic strains in nanocrystal spheres and rods. Strains at the
      percent level are observed in CdS and CdSe samples, associated with a rapid
      expansion followed by contraction along the nanosphere or nanorod radial
      direction driven by a transient carrier-induced stress. These morphological
      changes occur simultaneously with the first steps in the melting transition on
      hundreds of femtosecond timescales. This work represents the first direct real
      time probe of the dynamics of these large-amplitude strains and shape changes in
      few-nanometre-scale particles. 

PMID- 25762349
TI  - Incidence and risk factors for hepatocellular carcinoma in primary biliary
      cirrhosis.
AB  - The incidence, risk factors, and clinical features of hepatocellular carcinoma
      (HCC) in primary biliary cirrhosis (PBC) have been a long-standing subject of
      interest. We took advantage of a large cohort of 1865 well-defined Chinese
      patients with PBC for whom follow-up was conducted for up to 20 years to study
      the incidence of HCC. Our goal was to address the incidence and prevalence of HCC
      in PBC and the risk factors, including hepatitis B virus (HBV) infection, and
      finally to compare the tumor characteristics of PBC-related HCC, including size,
      location, mortality, and long-term outcomes, to that of HBV-related HCC. In this
      cohort, HCC occurred in 70 of 1865 PBC patients with a prevalence of 3.75 % and
      an incidence of 0.66 cases per 100 patient-years. The 5- and 10-year cumulative
      incidences were 2.6 % (95 % confidence interval (CI) 1.8-3.4) and 8.9 % (95 % CI
      5.5-12.3), respectively. Age >54 years (odds ratio [OR] = 5.5, 95 % CI 3.0-10.1,
      p = 0.001), male sex (OR = 2.2, 95 % CI 1.2-4.0, p = 0.001), co-existence of
      diabetes mellitus (DM) (OR = 3.1, 95 % CI 1.6-6.2, p = 0.002), and previous HBV
      infection (OR = 6.6, 95 % CI 3.7-11.9, p = 0.001) were independently associated
      with the development of HCC. The tumor size, number, location, and 5-year
      survival were not significantly different in PBC-related HCC compared to HBV
      related HCC. Alpha-fetoprotein was elevated in only 20 % of the cases with PBC
      related HCC. Although HCC was uncommon, occurring in fewer than 5 % of patients,
      the risk is significantly increased by age, sex, DM, and past HBV infection.

PMID- 25762351
TI  - Supramolecular scaffolds on glass slides as sugar based rewritable sensors for
      bacteria.
AB  - We describe here the sugar functionalized beta-cyclodextrin-ferrocene glass
      slides as fully reversible bacterial biosensors under the influence of external
      adamantane carboxylic acid. The prototype d-mannose - E. coli ORN 178 and l
      fucose - P. aeruginosa interactions serve as a model to illustrate the new
      approach. 

PMID- 25762353
TI  - The positional relationship between facial nerve and round window niche in
      patients with congenital aural atresia and stenosis.
AB  - To investigate whether differences existing in the distance between facial nerve
      (FN) and round window niche opening among congenital aural atresia (CAA),
      congenital aural stenosis (CAS) and a normal control group and to assess its
      effect on the round window implantation of vibrant soundbridge, CT images of 10
      normal subjects (20 ears), 27 CAS patients (30 ears) and 25 CAA patients (30
      ears) were analyzed. The distances from the central point of round window niche
      opening to the terminal point of the horizontal segment, the salient point of
      pyramidal segment, the beginning point of the vertical segment, and the vertical
      segment of the facial nerve (abbreviate as OA, OB, OC, OE, respectively) were
      calculated based on three-dimensional reconstruction using mimics software. The
      results suggested that the pyramidal segment of the FN was positioned more
      closely to round window niche opening in patients with both CAA and CAS groups
      than that in control group, whereas there was no significant difference between
      CAA and CAS group (P < 0.05). The vertical portion of the FN was positioned more
      closely to round window niche opening in the CAA group than those in both the CAS
      and control groups with statistical significance (P < 0.05). Furthermore, the
      vertical portion of the FN was positioned more closely to round window niche
      opening in the CAS group than that in control group (P < 0.05). In conclusion,
      the dislocation between facial nerve and round window niche in patients with
      congenital auditory canal malformations could have significant effects on the
      round window implantation of vibrant soundbridge. Moreover, three-dimensional
      measurements and assessments before surgery might be helpful for a safer surgical
      approach and implantation of vibrant soundbridge.

PMID- 25762352
TI  - Radiosensitization by BRAF inhibitor therapy-mechanism and frequency of toxicity
      in melanoma patients.
AB  - BACKGROUND: Recent evidence suggests that ionizing radiation may be associated
      with unexpected side-effects in melanoma patients treated with concomitant BRAF
      inhibitors. A large multicenter analysis was carried out to generate reliable
      safety data and elucidate the mechanism. METHODS: A total of 161 melanoma
      patients from 11 European skin cancer centers were evaluated for acute and late
      toxicity, of whom 70 consecutive patients received 86 series of radiotherapy with
      concomitant BRAF inhibitor therapy. To further characterize and quantify a
      possible radiosensitization by BRAF inhibitors, blood samples of 35 melanoma
      patients were used for individual radiosensitivity testing by fluorescence in
      situ hybridization of chromosomal breaks after ex vivo irradiation. RESULTS: With
      radiotherapy and concomitant BRAF inhibitor therapy the rate of acute
      radiodermatitis >=2 degrees  was 36% and follicular cystic proliferation was seen
      in 13% of all radiotherapies. Non-skin toxicities included hearing disorders (4%)
      and dysphagia (2%). Following whole-brain radiotherapy, rates of radiodermatitis
      >=2 degrees  were 44% and 8% (P < 0.001) for patients with and without BRAF
      inhibitor therapy, respectively. Concomitant treatment with vemurafenib induced
      acute radiodermatitis >=2 degrees  more frequently than treatment with dabrafenib
      (40% versus 26%, P = 0.07). In line with these findings, analysis of chromosomal
      breaks ex vivo indicated significantly increased radiosensitivity for patients
      under vemurafenib (P = 0.004) and for patients switched from vemurafenib to
      dabrafenib (P = 0.002), but not for patients on dabrafenib only. No toxicities
      were reported after stereotactic treatment. CONCLUSION: Radiotherapy with
      concomitant BRAF inhibitor therapy is feasible with an acceptable increase in
      toxicity. Vemurafenib is a more potent radiosensitizer than dabrafenib.

PMID- 25762354
TI  - Changes in GDPase/UDPase enzymatic activity in response to oxidative stress in
      four Candida species.
AB  - The terminal processing of proteins and lipids occurs in the Golgi apparatus and
      involves the transport of sugar nucleotides into the Golgi lumen by specific
      carriers and the accumulation of nucleoside diphosphates (NDPs) as a result of
      oligosaccharide-protein glycosyltransferase activity. NDPs are converted into the
      corresponding nucleoside monophosphates (NMPs) by nucleoside diphosphatases
      (NDPases), thus relieving inhibition of sugar transferases. In addition, NMPs are
      then exchanged for equimolecular amounts of cytosolic sugar nucleotides by
      antiport transport systems. NDPases, commonly GDPase and UDPase, thus play a
      critical role in glycoprotein maturation and may influence fungal pathogenesis,
      morphogenesis, and cell wall properties. Interest of this laboratory has recently
      focused on the effect of reactive oxygen species (ROS) on enzymes involved in
      detoxification of these oxidants and on the metabolism of biomolecules such as
      lipids, nucleic acids, and proteins in human pathogenic Candida species. We
      therefore consider it important to extend these studies to determine how GDPase
      and UDPase are affected after exposure of cells to oxidants such as menadione, a
      superoxide (O2 (*-))-generator, and H2O2. Results indicate that activity of both
      enzymes decrease in response to these agents suggesting that ROS may also affect
      other critical cell functions such as protein glycosylation.

PMID- 25762355
TI  - Baseline hydration status in incident peritoneal dialysis patients: the
      initiative of patient outcomes in dialysis (IPOD-PD study)?.
AB  - BACKGROUND: Non-euvolaemia in peritoneal dialysis (PD) patients is associated
      with elevated mortality risk. There is an urgent need to collect data to help us
      understand the association between clinical practices and hydration and
      nutritional status, and their effects on patient outcome. METHODS: The aim of
      this prospective international, longitudinal observational cohort study is to
      follow up the hydration and nutritional status, as measured by bioimpedance
      spectroscopy using the body composition monitor (BCM) of incident PD patients for
      up to 5 years. Measures of hydration and nutritional status and of clinical,
      biochemical and therapy-related data are collected directly before start of PD
      treatment, at 1 and 3 months, and then every 3 months. This paper presents the
      protocol and a pre-specified analysis of baseline data of the cohort. RESULTS: A
      total of 1092 patients (58.1% male, 58.0 +/- 15.3 years) from 135 centres in 32
      countries were included. Median fluid overload (FO) was 2.0 L (males) and 0.9 L
      (females). Less than half of the patients were normohydrated (38.7%), whereas FO
      > 1.1 L was seen in 56.5%. Systolic and diastolic blood pressure were 139.5 +/-
      21.8 and 80.0 +/- 12.8 mmHg, respectively, and 25.1% of patients had congestive
      heart failure [New York Heart Association (NYHA) 1 or higher]. A substantial
      number of patients judged to be not overhydrated on clinical judgement appeared
      to be overhydrated by BCM measurement. Overhydration at baseline was
      independently associated with male gender and diabetic status. CONCLUSIONS: The
      majority of patients starting on PD are overhydrated already at start of PD. This
      may have important consequences on clinical outcomes and preservation of residual
      renal function. Substantial reclassification of hydration status by BCM versus on
      a clinical basis was necessary, especially in patients who were not overtly
      overhydrated. Both clinical appreciation and bioimpedance should be combined in
      clinical decision-making on hydration status.

PMID- 25762356
TI  - Immunity in arterial hypertension: associations or causalities?
AB  - Numerous studies describe associations between markers of inflammation and
      arterial hypertension (aHT), but does that imply causality? Interventional
      studies that reduce blood pressure reduced also markers of inflammation, but does
      immunosuppression improve hypertension? Here, we review the available mechanistic
      data. Aberrant immunity can trigger endothelial dysfunction but is hardly ever
      the primary cause of aHT. Innate and adaptive immunity get involved once
      hypertension has caused vascular wall injury as immunity is a modifier of
      endothelial dysfunction and vascular wall remodelling. As vascular remodelling
      progresses, immunity-related mechanisms can become significant cofactors for
      cardiovascular (CV) disease progression; vice versa, suppressing immunity can
      improve hypertension and CV outcomes. Innate and adaptive immunity both
      contribute to vascular wall remodelling. Innate immunity is driven by danger
      signals that activate Toll-like receptors and other pattern-recognition
      receptors. Adaptive immunity is based on loss of tolerance against vascular
      autoantigens and includes autoreactive T-cell immunity as well as non-HLA
      angiotensin II type 1 receptor-activating autoantibodies. Such processes involve
      numerous other modulators such as regulatory T cells. Together, immunity is not
      causal for hypertension but rather an important secondary pathomechanism and a
      potential therapeutic target in hypertension. 

PMID- 25762357
TI  - Platelet-rich fibrin with 1% metformin for the treatment of intrabony defects in
      chronic periodontitis: a randomized controlled clinical trial.
AB  - BACKGROUND: Platelet-rich fibrin (PRF) is a second-generation platelet
      concentrate that releases various growth factors that promote tissue
      regeneration. Metformin (MF), a member of the biguanide group, has been shown to
      facilitate osteoblast differentiation and thus may exhibit a favorable effect on
      alveolar bone. The current study is designed to evaluate the efficacy of open
      flap debridement (OFD) combined with PRF, 1% MF gel, and PRF + 1% MF gel in the
      treatment of intrabony defects (IBDs) in patients with chronic periodontitis
      (CP). METHODS: One hundred twenty patients with single defects were categorized
      into four treatment groups: OFD alone, OFD with PRF, OFD with 1% MF, and OFD with
      PRF plus 1% MF. Clinical parameters such as site-specific plaque index (PI),
      modified sulcus bleeding index (mSBI), probing depth (PD), relative attachment
      level (RAL), and gingival marginal level (GML) were recorded at baseline (before
      surgery) and 9 months postoperatively. Percentage radiographic IBD depth
      reduction was evaluated using computer-aided software at baseline and 9 months.
      RESULTS: PRF, 1% MF, and PRF + 1% MF groups showed significantly more PD
      reduction and RAL gain than the OFD-only group. Mean PD reduction and mean RAL
      gain were found to be greater in the PRF + 1% MF group compared to just PRF or MF
      at 9 months. Furthermore, PRF + 1% MF group sites showed a significantly greater
      percentage of radiographic defect depth reduction (52.65% +/- 0.031%) compared to
      MF (48.69% +/- 0.026%), PRF (48% +/- 0.029%), and OFD alone (9.14% +/- 0.04%) at
      9 months. CONCLUSION: The PRF + 1% MF group showed greater improvements in
      clinical parameters, with greater percentage radiographic defect depth reduction
      compared to MF, PRF, or OFD alone in treatment of IBDs in patients with CP.

PMID- 25762358
TI  - Associations between serum 25-hydroxyvitamin d and periodontal pocketing and
      gingival bleeding: results of a study in a non-smoking population in Finland.
AB  - BACKGROUND: Apart from the effects of vitamin D on bone metabolism, it is also
      known for its immunomodulatory properties. However, so far, it is not clear
      whether serum 25-hydroxyvitamin D [25(OH)D] exerts any beneficial effect on the
      periodontium. The aim of the present study is to investigate whether the serum
      level of 25(OH)D is related to periodontal condition, measured by means of
      pocketing and gingival bleeding. METHODS: This cross-sectional study is based on
      a non-smoking subpopulation without diabetes of the Finnish Health 2000 Survey (N
      = 1,262). Periodontal condition was measured as the number of teeth with deep
      (>=4 mm) periodontal pockets and the number of bleeding sextants per individual.
      Serum 25(OH)D level was determined by means of a standard laboratory measurement.
      Prevalence rate ratios and 95% confidence intervals were estimated using Poisson
      regression models. RESULTS: There were practically no associations between serum
      25(OH)D level and teeth with deep (>=4 mm) periodontal pockets or bleeding
      sextants. A somewhat lower proportion of teeth with deep periodontal pockets was
      found in higher serum 25(OH)D quintiles among individuals with a good oral
      hygiene level. CONCLUSION: Serum 25(OH)D did not seem to be related to
      periodontal condition, measured as periodontal pocketing and gingival bleeding in
      this low-risk, low-25(OH)D status population.

PMID- 25762359
TI  - Microbiologic Observations After Four Treatment Strategies Among Patients With
      Periodontitis Maintaining a High Standard of Oral Hygiene: Secondary Analysis of
      a Randomized Controlled Clinical Trial.
AB  - BACKGROUND: The benefit of full-mouth disinfection (FDIS) over traditional
      scaling and root planing (SRP), with or without adjunctive metronidazole, when
      treating chronic destructive periodontitis remains equivocal, as does the long
      term association between clinical and microbiologic outcomes after such
      strategies. The aim of this study is to examine the relationship between clinical
      and microbiologic outcomes of four different treatment strategies for chronic
      destructive periodontitis among patients who maintain excellent oral hygiene and
      low gingival bleeding scores. METHODS: One hundred eighty-four patients with
      periodontitis and capable of maintaining a high standard of oral hygiene were
      randomly allocated to one of four treatment groups: 1) FDIS + metronidazole; 2)
      FDIS + placebo; 3) SRP + metronidazole; and 4) SRP + placebo. Recordings of
      plaque, bleeding on probing, probing depth (PD), and clinical attachment level
      were carried out in four sites per tooth at baseline, 3 and 12 months after
      treatment. Before treatment, pooled subgingival samples were obtained from the
      five deepest pockets, which were sampled again 3 and 12 months after treatment.
      Microbiologic assessments of eight putative periodontal pathogens were performed
      using the checkerboard DNA-DNA hybridization method. RESULTS: Levels of bacterial
      species were already relatively low at baseline. The only microbial factor
      statistically significantly associated with the clinical outcomes of treatment
      after 12 months was the association between reductions of Tannerella forsythia
      and being free from PD >=5 mm. CONCLUSION: In this clinical trial, the only
      microbial factor associated with the clinical outcomes after 12 months was a
      statistically significant association between the reductions of T. forsythia and
      being free from PD >=5 mm.

PMID- 25762360
TI  - Love it or hate it!

PMID- 25762361
TI  - Electron doping in bottom-up engineered thermoelectric nanomaterials through HCl
      mediated ligand displacement.
AB  - A simple and effective method to introduce precise amounts of doping in
      nanomaterials produced from the bottom-up assembly of colloidal nanoparticles
      (NPs) is described. The procedure takes advantage of a ligand displacement step
      to incorporate controlled concentrations of halide ions while removing carboxylic
      acids from the NP surface. Upon consolidation of the NPs into dense pellets,
      halide ions diffuse within the crystal structure, doping the anion sublattice and
      achieving n-type electrical doping. Through the characterization of the
      thermoelectric properties of nanocrystalline PbS, we demonstrate this strategy to
      be effective to control charge transport properties on thermoelectric
      nanomaterials assembled from NP building blocks. This approach is subsequently
      extended to PbTe(x)Se(1-x)@PbS core-shell NPs, where a significant enhancement of
      the thermoelectric figure of merit is achieved.

PMID- 25762363
TI  - Cost-effectiveness Analysis with Influence Diagrams.
AB  - BACKGROUND: Cost-effectiveness analysis (CEA) is used increasingly in medicine to
      determine whether the health benefit of an intervention is worth the economic
      cost. Decision trees, the standard decision modeling technique for non-temporal
      domains, can only perform CEA for very small problems. OBJECTIVE: To develop a
      method for CEA in problems involving several dozen variables. METHODS: We explain
      how to build influence diagrams (IDs) that explicitly represent cost and
      effectiveness. We propose an algorithm for evaluating cost-effectiveness IDs
      directly, i.e., without expanding an equivalent decision tree. RESULTS: The
      evaluation of an ID returns a set of intervals for the willingness to pay -
      separated by cost-effectiveness thresholds - and, for each interval, the cost,
      the effectiveness, and the optimal intervention. The algorithm that evaluates the
      ID directly is in general much more efficient than the brute-force method, which
      is in turn more efficient than the expansion of an equivalent decision tree.
      Using OpenMarkov, an open-source software tool that implements this algorithm, we
      have been able to perform CEAs on several IDs whose equivalent decision trees
      contain millions of branches. CONCLUSION: IDs can perform CEA on large problems
      that cannot be analyzed with decision trees.

PMID- 25762362
TI  - Lynch syndrome associated with two MLH1 promoter variants and allelic imbalance
      of MLH1 expression.
AB  - Lynch syndrome is a hereditary cancer syndrome caused by a constitutional
      mutation in one of the mismatch repair genes. The implementation of predictive
      testing and targeted preventative surveillance is hindered by the frequent
      finding of sequence variants of uncertain significance in these genes. We aimed
      to determine the pathogenicity of previously reported variants (c.-28A>G and c.
      7C>T) within the MLH1 5'untranslated region (UTR) in two individuals from
      unrelated suspected Lynch syndrome families. We investigated whether these
      variants were associated with other pathogenic alterations using targeted high
      throughput sequencing of the MLH1 locus. We also determined their relationship to
      gene expression and epigenetic alterations at the promoter. Sequencing revealed
      that the c.-28A>G and c.-7C>T variants were the only potentially pathogenic
      alterations within the MLH1 gene. In both individuals, the levels of
      transcription from the variant allele were reduced to 50% compared with the wild
      type allele. Partial loss of expression occurred in the absence of constitutional
      epigenetic alterations within the MLH1 promoter. We propose that these variants
      may be pathogenic due to constitutional partial loss of MLH1 expression, and that
      this may be associated with intermediate penetrance of a Lynch syndrome
      phenotype. Our findings provide further evidence of the potential importance of
      noncoding variants in the MLH1 5'UTR in the pathogenesis of Lynch syndrome.

PMID- 25762364
TI  - Cytokine-Enhanced Vaccine and Interferon-beta plus Suicide Gene Therapy as
      Surgery Adjuvant Treatments for Spontaneous Canine Melanoma.
AB  - We present here a nonviral immunogene therapy trial for canine malignant
      melanoma, an aggressive disease displaying significant clinical and
      histopathological overlapping with human melanoma. As a surgery adjuvant
      approach, it comprised the co-injection of lipoplexes bearing herpes simplex
      virus thymidine kinase and canine interferon-beta genes at the time of surgery,
      combined with the periodic administration of a subcutaneous genetic vaccine
      composed of tumor extracts and lipoplexes carrying the genes of human interleukin
      2 and human granulocyte-macrophage colony-stimulating factor. Following complete
      surgery (CS), the combined treatment (CT) significantly raised the portion of
      local disease-free canine patients from 11% to 83% and distant metastases-free
      (M0) from 44% to 89%, as compared with surgery-only-treated controls (ST). Even
      after partial surgery (PS), CT better controlled the systemic disease (M0: 82%)
      than ST (M0: 48%). Moreover, compared with ST, CT caused a significant 7-fold
      (CS) and 4-fold (PS) rise of overall survival, and >17-fold (CS) and >13-fold
      (PS) rise of metastasis-free survival. The dramatic increase of PS metastasis
      free survival (>1321 days) and CS recurrence- and metastasis-free survival (both
      >2251 days) demonstrated that CT was shifting a rapidly lethal disease into a
      chronic one. In conclusion, this surgery adjuvant CT was able of significantly
      delaying or preventing postsurgical recurrence and distant metastasis, increasing
      disease-free and overall survival, and maintaining the quality of life. The high
      number of canine patients involved in CT (301) and the extensive follow-up (>6
      years) with minimal or absent toxicity warrant the long-term safety and efficacy
      of this treatment. This successful clinical outcome justifies attempting a
      similar scheme for human melanoma. 

PMID- 25762365
TI  - Placental hypoxic overlap lesions: a clinicoplacental correlation.
AB  - AIM: This retrospective analysis is aimed to study clinical and placental
      associations of placental acute, chronic, and acute-on-chronic (overlap) hypoxic
      lesions. MATERIAL AND METHODS: Frequencies of 32 clinical (maternal and fetal)
      and 47 placental (gross and microscopic) phenotypes were compared by the Yates
      chi(2) with the Holm-Bonferroni correction among consecutive placentas from 2831
      >= 16-week gestations: 778 placentas with chronic hypoxic lesion(s) (diffuse
      patterns of hypoxic placental injury, chorangiosis, excessive extravillous
      trophoblasts, microscopic chorionic pseudocysts, clusters of decidual
      multinucleate trophoblasts), 481 placentas with acute hypoxic lesion(s)
      (infarction, intravillous hemorrhage, deep meconium penetration, membrane laminar
      necrosis), 585 placentas with hypoxic overlap lesion(s) (coexisting at least one
      lesion from each of the above groups), and 987 placentas without placental
      hypoxic lesions, adjusted for gestational age. RESULTS: The control group was
      dominated by premature rupture of membranes, inflammatory pattern of placental
      injury, and poor prenatal care. The fetal and placental hypoxic patterns were
      associated not only with increased frequency of clinical hypoxia-associated
      conditions, but also abnormal umbilical cord coiling, intervillous thrombi,
      retroplacental hematomas, and placental features of fetal thrombotic
      vasculopathy, particularly in association with hypoxic overlap lesions.
      CONCLUSION: Placental hypoxic overlap lesions are associated with clinical
      complications of pregnancy and predispose to thrombotic lesions, some most likely
      stasis-induced.

PMID- 25762368
TI  - Extensive pericardial fat tissue mimicking paracardiac mass.

PMID- 25762369
TI  - Chemical quality assessment of traditional salt-fermented shrimp paste from
      Northern Mindanao, Philippines.
AB  - BACKGROUND: Shrimp paste is an important fermented commodity in the Philippines,
      but so far its quality parameters have hardly been characterized. In this study,
      paste samples procured in the province of Agusan del Norte, Philippines from
      three different traditional manufacturers and from a commercial supermarket were
      analyzed for their chemical composition. RESULTS: Both traditional and commercial
      shrimp pastes varied in their content of protein (12.9-15.3 g per 100 g), fat
      (0.50-1.94 g per 100 g), saturated fatty acids (32.6-39.1 g per 100 g fatty acid
      methyl esters (FAME)), monounsaturated fatty acids (15.1-18.7 g per 100 g FAME)
      and polyunsaturated fatty acids (30.7-40.8 g per 100 g FAME). Their pH ranged
      between 6.8 and 7.7. The samples were microbiologically stable owing to their low
      water activity (0.70-0.74) and high NaCl content (4.04-5.15 g per 100 g).
      Although all samples were processed in the same country and under similar
      conditions, differences were observed in some parameters: thiobarbituric acid
      reactive substances (2.32-5.03 ug malondialdehyde g(-1)), total non-protein
      nitrogen (3.07-5.15 g N per 100 g), free non-protein nitrogen (1.17-2.39 g N per
      100 g), biogenic amines and mineral content. The biogenic amine index varied
      between 0 and 976 for the different samples; only one sample could be considered
      as class 1 quality. CONCLUSION: The results showed that there is a high variation
      in the quality of the product which could be linked to differences in the
      fermentation process and hygienic quality.

PMID- 25762371
TI  - Transtympanic dilatation of the eustachian tube during chronic ear surgery.
AB  - CONCLUSION: Evaluation of the protympanic segment of the eustachian tube is
      feasible during chronic ear surgery. Balloon dilatation of that segment yields a
      bigger aperture. OBJECTIVE: To evaluate the feasibility of visualization and
      balloon dilatation of the protympanic segment of the eustachian tube during
      chronic ear surgery. METHODS: This study was carried out on a consecutive case
      series. All patients undergoing surgical treatment for cholesteatoma or tympanic
      membrane perforation over a 6-month period of time at a tertiary hospital were
      evaluated intraoperatively for the ability to visualize the protympanic segment
      of the eustachian tube, perform balloon dilatation, and then perform visual
      inspection of the effect of dilatation. RESULTS: A total of 21 chronic ear
      procedures were performed; visualization of the protympanic segment was feasible
      in 12 ears, obstruction was identified in 7 ears, and dilatation was undertaken.
      Immediate assessment showed increased aperture of the tube in all patients when
      compared with predilatation findings.

PMID- 25762370
TI  - Removal of nuisance signals from limited and sparse 1H MRSI data using a union-of
      subspaces model.
AB  - PURPOSE: To remove nuisance signals (e.g., water and lipid signals) for (1) H
      MRSI data collected from the brain with limited and/or sparse (k, t)-space
      coverage. METHODS: A union-of-subspace model is proposed for removing nuisance
      signals. The model exploits the partial separability of both the nuisance signals
      and the metabolite signal, and decomposes an MRSI dataset into several sets of
      generalized voxels that share the same spectral distributions. This model enables
      the estimation of the nuisance signals from an MRSI dataset that has limited
      and/or sparse (k, t)-space coverage. RESULTS: The proposed method has been
      evaluated using in vivo MRSI data. For conventional chemical shift imaging data
      with limited k-space coverage, the proposed method produced "lipid-free" spectra
      without lipid suppression during data acquisition at 130 ms echo time. For sparse
      (k, t)-space data acquired with conventional pulses for water and lipid
      suppression, the proposed method was also able to remove the remaining water and
      lipid signals with negligible residuals. CONCLUSION: Nuisance signals in (1) H
      MRSI data reside in low-dimensional subspaces. This property can be utilized for
      estimation and removal of nuisance signals from (1) H MRSI data even when they
      have limited and/or sparse coverage of (k, t)-space. The proposed method should
      prove useful especially for accelerated high-resolution (1) H MRSI of the brain.

PMID- 25762372
TI  - Distribution and impact of yeast thermal tolerance permissive for mammalian
      infection.
AB  - BACKGROUND: From the viewpoint of fungal virulence in mammals, thermal tolerance
      can be defined as the ability to grow in the 35 degrees C to 40 degrees C range,
      which is essential for inhabiting these hosts. RESULTS: We used archival
      information in a fungal collection to analyze the relationship between thermal
      tolerance and genetic background for over 4,289 yeast strains belonging to 1,054
      species. Fungal genetic relationships were inferred from hierarchical trees based
      on pairwise alignments using the rRNA internal transcribed spacer and large
      subunit rDNA (LSU) sequences. In addition, we searched for correlations between
      thermal tolerance and other archival information including antifungal
      susceptibility, carbon sources, and fermentative capacity. Thermal tolerance for
      growth at mammalian temperatures was not monophyletic, with thermally tolerant
      species being interspersed among families that include closely related species
      that are not thermal tolerant. Thermal tolerance and resistance to antifungal
      drugs were not correlated, suggesting that these two properties evolved
      independently. Nevertheless, the ability to grow at higher temperatures did
      correlate with origin from lower geographic latitudes, capacity for fermentation
      and assimilation of certain carbon sources. CONCLUSIONS: Thermal tolerance was
      significantly more common among ascomycetous than basidiomycetous yeasts,
      suggesting an explanation for the preponderance of ascomycetous yeasts among
      human pathogenic fungi. Analysis of strain maximum tolerable temperature as a
      function of collection time suggested that basidiomycetous yeasts are rapidly
      adapting to global warming. The analysis identified genera with a high prevalence
      of the thermal-tolerant species that could serve as sources of emerging
      pathogenic fungi.

PMID- 25762373
TI  - Contribution of the Runx1 transcription factor to axonal pathfinding and muscle
      innervation by hypoglossal motoneurons.
AB  - The runt-related transcription factor Runx1 contributes to cell type
      specification and axonal targeting projections of the nociceptive dorsal root
      ganglion neurons. Runx1 is also expressed in the central nervous system, but
      little is known of its functions in brain development. At mouse embryonic day (E)
      17.5, Runx1-positive neurons were detected in the ventrocaudal subdivision of the
      hypoglossal nucleus. Runx1-positive neurons lacked calcitonin gene-related
      peptide (CGRP) expression, whereas Runx1-negative neurons expressed CGRP.
      Expression of CGRP was not changed in Runx1-deficient mice at E17.5, suggesting
      that Runx1 alone does not suppress CGRP expression. Hypoglossal axon projections
      to the intrinsic vertical (V) and transverse (T) tongue muscles were sparser in
      Runx1-deficient mice at E17.5 compared to age-matched wild-type littermates.
      Concomitantly, vesicular acetylcholine transporter-positive axon terminals and
      acetylcholine receptor clusters were less dense in the V and T tongue muscles of
      Runx1-deficient mice. These abnormalities in axonal projection were not caused by
      a reduction in the total number hypoglossal neurons, failed synaptogenesis, or
      tongue muscles deficits. Our results implicate Runx1 in the targeting of
      ventrocaudal hypoglossal axons to specific tongue muscles. However, Runx1
      deficiency did not alter neuronal survival or the expression of multiple
      motoneuron markers as in other neuronal populations. Thus, Runx1 appears to have
      distinct developmental functions in different brain regions.

PMID- 25762374
TI  - Colonoscopy findings in high-risk individuals compared to an average-risk control
      population.
AB  - BACKGROUND AND AIMS: There is clear evidence of reduced morbidity and mortality
      from regular colonoscopy programs in patients with Lynch syndrome (LS). Today,
      also individuals with empirically increased risks of colorectal cancer (CRC) are
      offered colonoscopic surveillance. The aim was to compare the findings at the
      first screening colonoscopy in LS carriers, and individuals with an increased
      risk of bowel cancer due to family history of CRC with a control population.
      METHODS: Altogether 1397 individuals with an increased risk for CRC were divided
      in four risk groups: one with LS carriers and three groups with individuals with
      different family history of CRC. The findings were compared between the different
      risk groups and a control group consisting of 745 individuals from a control
      population who took part in a population-based colonoscopy study. RESULTS: In LS,
      30% of the individuals had adenomas and 10% advanced adenomas. The corresponding
      figures in the other risk groups were 14-24% and 4-7%, compared with 10% and 3%
      in the control group. The relative risk of having adenomas and advanced adenomas
      was, compared to controls, significantly higher for all risk groups except the
      group with the lowest risk. Age was a strong predictor for adenomas and advanced
      adenomas in both risk individuals and controls. CONCLUSIONS: Individuals with a
      family history of CRC have a high prevalence and cumulative risk of adenomas and
      advanced adenomas, and screening is motivated also in this risk group.

PMID- 25762375
TI  - An adenosine A3 receptor agonist inhibits DSS-induced colitis in mice through
      modulation of the NF-kappaB signaling pathway.
AB  - The role of the adenosine A3 receptor (A3AR) in experimental colitis is
      controversial. The A3AR agonist N(6)-(3-iodobenzyl)adenosine-5'-N-methyluronamide
      (IB-MECA) has been shown to have a clinical benefit, although studies in A3AR
      deficient mice suggest a pro-inflammatory role. However, there are no studies on
      the effect of 2-Cl-IB-MECA and the molecular mechanism of action of A3AR in
      murine colitis models in vivo. Is it the same as that observed in vitro? The
      interaction between 2-CL-IB-MECA and A3AR in a murine colitis model and the
      signaling pathways associated with this interaction remain unclear. Here we
      demonstrate a role for the NF-kappaB signaling pathway and its effect on
      modifying the activity of proinflammatory factors in A3AR-mediated biological
      processes. Our results demonstrated that A3AR activation possessed marked effects
      on experimental colitis through the NF-kappaB signaling pathway. 

PMID- 25762377
TI  - In reply: Confirmation of endotracheal tube depth using ultrasound in adults.

PMID- 25762376
TI  - Confirmation of endotracheal tube depth using ultrasound in adults.

PMID- 25762378
TI  - Characterizing non-photochemical quenching in leaves through fluorescence
      lifetime snapshots.
AB  - We describe a technique to measure the fluorescence decay profiles of intact
      leaves during adaptation to high light and subsequent relaxation to dark
      conditions. We show how to ensure that photosystem II reaction centers are closed
      and compare data for wild type Arabidopsis thaliana with conventional pulse
      amplitude modulated (PAM) fluorescence measurements. Unlike PAM measurements, the
      lifetime measurements are not sensitive to photobleaching or chloroplast
      shielding, and the form of the fluorescence decay provides additional information
      to test quantitative models of excitation dynamics in intact leaves. 

PMID- 25762379
TI  - Determination of Rare Earth Elements in Human Sperm and Association with Semen
      Quality.
AB  - The aim of the present study was to measure lanthanum (La), cerium (Ce), europium
      (Eu), and gadolinium (Gd) concentrations in human semen and correlate the results
      with sperm quality. The median semen content of La was 19.5 ug kg(-1) dry weight
      (dw) (range 2.27-269), of Ce was 41.9 ug kg(-1) dw (range 4.52 to 167), of Eu was
      0.68 ug kg(-1) dw (range 0.06-1.95), of Gd was 3.19 ug kg(-1) dw (range 0.38
      12.0), and of calcium (Ca) was 4063 mg kg(-1) dw (range 484-17,191).
      Concentrations of La, Ce, Eu, Gd, and Ca were significantly lower in nondrinkers'
      semen than in semen from drinkers. Significant differences were detected between
      La, Ce, Eu, Gd, and Ca concentrations in semen from nondrinkers and moderate
      drinkers. Concentrations of La, Ce, and Gd in semen of short-term smokers were
      significantly lower than those in extremely long-term smokers. Significant
      differences were also detected between La concentration in semen from a group of
      short-term smokers and that of a group of long-term smokers. Positive
      correlations were found between La, Ce, Eu, Gd, and Ca concentrations in semen.
      La, Ce, Gd, and Ca concentrations in semen were positively associated with
      progressive motility and percentage of normal spermatozoa. Positive correlations
      were found between Ca and sperm concentration. Concentrations of La, Ce, and Gd
      were negatively associated with sperm concentration, whilst Ca concentration was
      negatively associated with volume of ejaculate. At the examined level, La, Ce,
      Eu, and Gd did not affect sperm quality, whereas alcohol consumption and smoking
      might have increased the level of rare earth elements in semen. 

PMID- 25762380
TI  - Narrative health psychology: once more unto the breach. Introduction.
AB  - In this editorial, we position narrative health psychology as a variety of
      narrative psychology, a form of qualitative research in health psychology, and a
      psychological perspective that falls under the interdisciplinary term narrative
      health research. The aim of this positioning is to explore what are the most
      important features of the proposed approach and how they are relevant. We
      illustrate each positioning with the scope and diversity of narrative health
      psychology brought together in this special issue. Finally, we reflect on where
      narrative health psychology is now and how it could develop in the future. 

PMID- 25762381
TI  - A breath of fresh air: images of respiratory illness in novels, poems, films,
      music, and paintings.
AB  - The nature and severity of respiratory disease are typically expressed with
      biomedical measures such as pulmonary function, X-rays, blood tests, and other
      physiological characteristics. The impact of respiratory illness on the sufferer,
      however, is reflected in the stories patients tell: to themselves, their social
      environment, and their health care providers. Behavioral research often applies
      standardized questionnaires to assess this subjective impact. Additional
      approaches to sampling patients' experience of respiratory illness may, however,
      provide important and clinically useful information that is not captured by other
      methods. Herein, we assert that novels, poems, movies, music, and paintings may
      represent a rich, experiential understanding of the patient's point of view of
      asthma, cystic fibrosis, lung cancer, and tuberculosis. Examination of these
      works illustrates the broad range and major impact of respiratory illness on
      patients' quality of life. We suggest that examining how illness is represented
      in various art forms may help patients, their social environment, and their
      health care providers in coping with the illness and in humanizing medical care.
      Medical students' clinical skills may benefit when illness experiences as
      expressed in art are incorporated in the medical curriculum. More generally,
      Narrative Health Psychology, Narrative Medicine, and Medical Humanities deserve
      more attention in education, training, and clinical care of (respiratory)
      physicians, medical students, and other health care professionals. 

PMID- 25762382
TI  - Definitional ceremonies: narrative practices for psychologists to inform
      interdisciplinary teams' understanding of children's spirituality in pediatric
      settings.
AB  - In pediatric settings, parents and children often seek spiritual and religious
      support from their healthcare provider, as they try to find meaning in their
      illness. Narrative practices, such as definitional ceremonies, can provide a
      unique framework for psychologists to explore children's spirituality and its
      role in the midst of illness. In addition, definitional ceremonies can be used as
      a means for psychologists to inform interdisciplinary teams' understanding of
      children's spirituality and its relevance in pediatric treatment settings. In
      this article, our objectives are to (a) provide a brief overview of the
      literature on children's spirituality, (b) review some of the literature on
      childhood cancer patients' spirituality, (c) highlight the importance of whole
      person care for diverse pediatric patients, and (d) introduce definitional
      ceremonies as appropriate narrative practices that psychologists can use to both
      guide their therapy and inform interdisciplinary teams' understanding of
      children's spirituality. 

PMID- 25762383
TI  - A narrative analysis of spiritual distress in geriatric physical rehabilitation.
AB  - Drawing upon narrative data generated in a semi-structured interview with an 82
      year-old female patient in geriatric physical rehabilitation, this clinical case
      study provides a detailed example of recognizing, assessing, and addressing
      spiritual distress as a symptom of physical pain. Data analysis focused on
      narrative content as well as on the interactive and performative aspects of
      narrating spiritual health issues in a close reading of two "attachment
      narratives." Results support the "narrative turn" in healthcare, including the
      therapeutic benefits of empathic listening as "narrative care" in geriatric
      rehabilitation and in healthcare in general. 

PMID- 25762384
TI  - Collective stories and well-being: using a dialogical narrative approach to
      understand peer relationships among combat veterans experiencing post-traumatic
      stress disorder.
AB  - Using a dialogical narrative approach, this original research explored how combat
      veterans experiencing post-traumatic stress disorder made sense of peer
      relationships with other veterans and what effects these relationships had on
      their well-being. Interviews and participant observations were conducted with 15
      male combat veterans (aged 27-60 years) and one member of the civilian emergency
      services, the majority of whom were diagnosed with post-traumatic stress disorder
      following traumatic exposure in a range of armed conflicts. All participants were
      part of a surfing charity for veterans experiencing post-traumatic stress
      disorder. Data were rigorously analysed using a dialogical narrative analysis
      (DNA). Findings revealed the collective story that veterans used to make sense of
      peer relationships within the group. This collective story worked for the
      veterans to shape their experiences of well-being by fostering camaraderie,
      stimulating deeper connections and countering the negative effects of post
      traumatic stress disorder. Potential therapeutic effects of the collective story
      were also identified. This article extends previous knowledge on combat veterans
      and social relationships and advances the field of narrative health psychology
      through the empirical application of a sophisticated dialogical narrative
      approach. 

PMID- 25762385
TI  - Problem gambling and help seeking among Chinese international students:
      narratives of place identity transformation.
AB  - This article uses examples of problem gambling and help seeking among Chinese
      international students in New Zealand to demonstrate place identity
      transformation. Two-wave narrative interviews were conducted with 15 Chinese
      international students. Place identity among participants is shown to be a
      process that features the transformation of participants' identity. While the
      casinos in which the Chinese international students gambled gave rise to negative
      place identities, positive place identities facilitated the participants to
      change their problematic gambling. Through the investigation of place identity
      transformation, this article promotes a strength-based, non-labelling approach to
      intervention for people who are concerned about their gambling behaviours. 

PMID- 25762386
TI  - Family experiences of living with an eating disorder: a narrative analysis.
AB  - Families are considered important in the management and treatment of eating
      disorders. Yet, rarely has research focused on family experiences of living with
      an eating disorder. Addressing this gap, this study explores the experiences of
      an elite 21-year-old triathlete with an eating disorder in conjunction with the
      experiences of her parents. Family members attended interviews individually on
      three separate occasions over the course of a year. In line with the narrative
      approach adopted, whereby stories are considered the primary means to construct
      experience, interviews encouraged storytelling through an open-ended, participant
      led structure. Narrative analysis involved repeated readings of the transcripts,
      sensitising towards issues of narrative content (key themes) and structure
      (overarching plot). Family difficulties arose when personal experiences strayed
      from culturally dominant narrative forms and when family members held contrasting
      narrative preferences. Suggestions are forwarded as to how an appreciation of
      eating disorder illness narratives might inform treatment and support. 

PMID- 25762387
TI  - Identity as "knowing your place": the narrative construction of space in a
      healthcare profession.
AB  - The construction of space in which a story takes place can have important
      consequences for the evaluation of health interventions. In this article, we
      explore the ways professionals narratively position themselves in a situation,
      treating identity literally as "knowing one's place." More specifically, we
      explore the spatial language health professionals use to describe their work.
      Using descriptions of professionals in a drug habilitation organization, we
      illustrate how they use route (i.e., an active tour through the space), survey
      (i.e., a stationary viewpoint from above), and gaze perspectives (i.e. a stable
      viewpoint onto a place) to explain the work situations they encounter. Each of
      these perspectives facilitates a different mode of evaluation in terms of
      distance, emotion, and identity. We propose opportunities for research and
      implications of the ways in which spaces and spatial perspectives set the scene
      in the narratives of healthcare professionals.

PMID- 25762388
TI  - The narrative psychology of community health workers.
AB  - Community health psychology is an approach which promotes community mobilisation
      as a means of enhancing community capacity and well-being and challenging health
      inequalities. Much of the research on this approach has been at the more
      strategic and policy level with less reference to the everyday experiences of
      community workers who are actively involved in promoting various forms of
      community change. This article considers the narrative accounts of a sample of 12
      community workers who were interviewed about their lives. Their accounts were
      analysed in terms of narrative content. This revealed the tensions in their
      everyday practice as they attempted to overcome community divisions and
      management demands for evidence. Common to all accounts was a commitment to
      social justice. These findings are discussed with reference to opportunities and
      challenges in the practice of community work. 

PMID- 25762389
TI  - Mapping letters from the future: exploring narrative processes of imagining the
      future.
AB  - This article uses Letters from the Future (a health promotion instrument) to
      explore the human capacity of imagining the future. From a narrative perspective,
      letters from the future are considered to be indicative of a variety of forms
      through which human beings construct and understand their future selves and
      worlds. This is consistent with an interpretive approach to understanding the
      human mind, which offers an alternative for the current dominant causal
      explanatory approach in psychology. On the basis of qualitative analysis of 480
      letters from the future, collected online from a diverse group of Dutch and
      German persons, we first identified five narrative processes operating in the
      letters: imagining, evaluating, orienting, expressing emotions and engaging in
      dialogue. Second, using comparative analysis, we identified six types of how
      these processes are organized in the letters as a whole. These types differ
      regarding functionality (which of the five processes was dominant); temporality
      (prospective, retrospective and present-oriented); the extent to which a path
      between present and future was described; and the vividness of the imagination.
      We suggest that these types can be used in narrative health practice as
      'pathways' to locate where letter writers are on their path to imagine the
      future, rather than as a normative taxonomy. Future research should focus on how
      these pathways can be used to navigate to health and well-being. 

PMID- 25762391
TI  - Video-assisted mediastinoscopic lymphadenectomy combined with minimally invasive
      pulmonary resection for left-sided lung cancer: feasibility and clinical impacts
      on surgical outcomes?.
AB  - OBJECTIVES: Although video-assisted mediastinoscopic lymphadenectomy (VAMLA) has
      greatly increased the accuracy of mediastinal staging, its clinical value as a
      therapeutic tool for complete mediastinal lymph node dissection in the treatment
      of left-sided lung cancer is not well elucidated. METHODS: We identified the
      consecutive 649 patients with left-sided lung cancer undergoing minimally
      invasive pulmonary resection between July 2002 and June 2013. Among them, 225
      patients underwent VAMLA combined with pulmonary resection (VAMLA + VATS group),
      while the remaining 424 patients underwent VATS procedure only (VATS group).
      Operative outcomes including procedural time, removed lymph nodes and node
      stations, complications and the final pathological mediastinal staging in the
      both groups were evaluated and compared. RESULTS: There was no significant
      difference in the baseline profiles between the two groups. The patients in the
      VATS + VAMLA group showed significantly shorter operative time (116.8 +/- 39.8 vs
      159.8 +/- 44 .0 min; P < 0.001), more extensive lymph node dissection (total
      number of removed lymph nodes, 29.7 +/- 10.8 vs 23.0 +/- 8.6; P < 0.001) and the
      higher rates of patients with mediastinal lymph nodes removed: Station 2 on the
      right (12.4 vs 0.2%), Station 2 on the left (15.1 vs 0.2%), Station 4 on the
      right (42.7 vs 0.9%), Station 4 on the left (87.6 vs 57.3%) and Station 7 (100 vs
      99.3%), while maintaining comparable surgical morbidities compared with the VATS
      group. Also, the patients in the VATS + VAMLA group tended to have higher rates
      of being upstaged with mediastinal involvement (8.0 vs 5.7%; P = 0.31).
      CONCLUSIONS: VAMLA is a clinically feasible procedure safely performed as a
      therapeutic tool for complete mediastinal lymph node dissection (MLND), and can
      be a good complement to minimally invasive pulmonary resection in left-sided lung
      cancer, where optimal MLND is not always feasible with VATS approach. Further
      studies are required to investigate the long-term clinical impacts of VAMLA with
      regard to survival and tumour recurrence.

PMID- 25762392
TI  - Contemporary long-term outcomes of an aggressive approach to mitral valve repair
      in children: is it effective and durable for both congenital and acquired mitral
      valve lesions?
AB  - OBJECTIVES: We analysed the long-term outcomes of mitral valve (MV) repair in
      children and compared the repairs for both congenital and acquired lesions.
      METHODS: A review of 634 children (<=18 years) who underwent MV repair from 1992
      to 2011 was conducted [excluding patients with complete atrioventricular septal
      defect (AVSD), single ventricle and atrioventricular (AV) discordance].
      Associated cardiac anomalies were present in 473 patients (75%). Congenital
      mitral lesions were found in 270 (43%) patients compared with an acquired
      aetiology in 364 (57%) [mainly rheumatic: 329 patients (90%)]. Mitral
      regurgitation (MR) was predominant in 606 (96%) patients, and 544 (86%) of these
      showed >=3+ MR. Modified techniques of MV reconstructions were used. RESULTS: The
      early mortality rate was 2% (14 patients). The mean follow-up was 55 months (1
      240 months; 85% complete). The late mortality rate was 4% (23 patients) and
      survival rates at 10 and 15 years were 91 and 86%, respectively. There was no
      significant difference in 10-year survival between repairing the congenital (98%)
      and acquired lesions (87%) (P = 0.17). The rate of freedom from reoperation after
      MV repair for the entire population was 79% at 10 years, with no significant
      difference between congenital (80%) and acquired lesions (79%) (P = 0.20). Fifty
      six patients (9%) required reoperation. Mixed MV lesions, commissural fusions and
      residual MR (>=2+) were the predictors of valve failure and reoperation. All
      survivors remain in New York Heart Association class I and none had
      thromboembolism or pacemaker insertion. CONCLUSIONS: MV repair can be
      successfully applied to both congenital and acquired MV disease in children.
      Aggressive repair techniques and avoidance of residual MR have improved
      durability and survival.

PMID- 25762393
TI  - Repair of acute type A aortic dissection in comatose patients.

PMID- 25762394
TI  - Structure and functioning of a multidisciplinary 'Heart Team' for patients with
      coronary artery disease: rationale and recommendations from a joint BCS/BCIS/SCTS
      working group.
AB  - The decision-making process in the management of patients with ischaemic heart
      disease has historically been the responsibility of the cardiologist and
      encompasses medical management, percutaneous coronary intervention (PCI) or
      coronary artery bypass surgery (CABG). Currently, there is significant
      geographical variability in the PCI:CABG ratio. There are now emerging
      recommendations that this decision-making process should be carried out through a
      multidisciplinary approach, namely the Heart Team. This work was carried out on
      behalf of The British Cardiovascular Society (BCS), Society for Cardiothoracic
      Surgery in Great Britain and Ireland (SCTS) and British Cardiovascular
      Intervention Society (BCIS). This manuscript sets out the principles for the
      functioning of the Heart Team. This work has been approved by the Executive
      Committees of BCS/BCIS/SCTS. 

PMID- 25762395
TI  - Defining the enigmatic annulus of the aortic valve.

PMID- 25762396
TI  - Equipoise between radial artery and right internal thoracic artery as the second
      arterial conduit in left internal thoracic artery-based coronary artery bypass
      graft surgery: a multi-institutional study?.
AB  - OBJECTIVES: Multiple arterial coronary artery grafting (MABG) improves long-term
      survival compared with single arterial CABG (SABG), yet the best second arterial
      conduit to be used with the left internal thoracic artery (LITA) remains
      undefined. Outcomes in patients grafted with radial artery (RA-MABG) versus right
      internal thoracic artery (RITA-MABG) as the second arterial graft were compared
      with SABG. METHODS: Multi-institutional, retrospective analysis of non-emergent
      isolated LITA to left anterior descending coronary artery CABG patients was
      performed using institutional Society of Thoracic Surgeon National Adult Cardiac
      Surgery Databases. 4484 (54.5%) SABG [LITA +/- saphenous vein grafts (SVG)], 3095
      (37.6%) RA-MABG (RA +/- SVG) and 641 (7.9%) RITA-MABG (RITA +/- SVG) patients
      were included. The RITA was used as a free (68%) or in situ (32%) graft. RA
      grafts were principally anastomosed to the ascending aorta. Long-term survival
      was ascertained from US Social Security Death Index and institutional follow-up.
      Triplet propensity matching and covariate-adjusted multivariate logistic
      regression were used to adjust for baseline differences between study cohorts.
      RESULTS: Compared with the SABG cohort, the RITA-MABG cohort was younger (58.6 +/
      10.2vs65.9 +/- 10.4, P < 0.001), had a higher prevalence of males (87% vs 65%, P
      < 0.001) and was generally healthier (MI: 36.7% vs 56.7%, P < 0.001, smoking:
      56.8% vs 61.1%, IDDM: 3.0% vs 14.4%, CVA: 2.6% vs 10.0%). The RA-MABG cohort was
      generally characterized by a risk profile intermediate to that of SABG and RlTA
      MABG. Unadjusted 5-, 10- and 15-year survival rates were best in RITA-MABG
      (95.2%, 89% and 82%), intermediate in RA-MABG (89%, 74%, 57%) and worst in SABG
      (82%, 61% and 44%) cohorts (all P < 0.001). Propensity matching yielded 551 RA
      MABG, RITA-MABG and SABG triplets, which showed similar 30-day mortality. Late
      survival (16 years) was equivalent in the RA-MABG and RITA-MABG cohorts [68.2% vs
      66.7%, P = 0.127, hazard ratio (HR) = 1.28 (0.96-1.71)] and both significantly
      better than SABG (61.1%). The corresponding SABG versus RITA-MABG and SABG versus
      RA-MABG HRs (95% confidence interval) were 1.52 (1.18-1.96) and 1.31 (1.01-1.69)
      with P < 0.002 and P = 0.038, respectively. CONCLUSIONS: RA-MABG or RITA-MABG
      equally improve long-term survival compared with SABG and thus should be embraced
      by the Heart Team as the therapy of choice in LITA-based coronary artery bypass
      surgery.

PMID- 25762397
TI  - Validation and quality measurements for EuroSCORE and EuroSCORE II in the Spanish
      cardiac surgical population: a prospective, multicentre study.
AB  - OBJECTIVES: Since its development in the late 1990s, the European System for
      Cardiac Operative Risk Evaluation (EuroSCORE) has been the predictive model of
      choice for estimating mortality after cardiac surgery. As outcomes from cardiac
      surgery improved, the EuroSCORE showed a loss of calibration, and a revised
      version of the model was developed, EuroSCORE II. The objectives of this study
      were to examine the validity of both scores in the Spanish population, and to
      depict the performance of both models on a funnel plot. METHODS: A prospective
      multicentre study was performed, with requests to participate sent to all centres
      in Spain. Participating centres reported the EuroSCORE, EuroSCORE II and the
      actual mortality of each patient. Incomplete data were requested to get a zero
      incidence of lost data. Calibration of models was evaluated with the Hosmer
      Lemeshow goodness-of-fit test, and discrimination with the areas under the
      receiver operating characteristic (ROC) curve. A funnel plot was constructed
      using mortality data from the 2010 European Registry, to represent risk-adjusted
      mortality. RESULTS: Twenty Spanish centres participated in the study; 4034
      patients undergoing cardiac surgery between 1 October 2012 and 31 March 2013 were
      collected. Prevalence of risk factors was analysed. The observed mortality rate
      was 6.5%. The mean additive EuroSCORE was 6.5. The mean expected mortality rate
      was 9.8% for the logistic EuroSCORE, and 5.7% for EuroSCORE II. Areas under the
      ROC curves were EuroSCORE: 0.77 [95% confidence interval (CI): 0.75-0.80],
      EuroSCORE II: 0.79 (95% CI: 0.76-0.82). Results for the goodness-of-fit test were
      EuroSCORE: 33.02 (P < 0.001), EuroSCORE II: 38.98 (P < 0.001). Risk-adjusted
      mortality is far beyond the lower bound of the CI if EuroSCORE is used as the
      reference model, and is between the confidence limits, but near to the upper
      bound when EuroSCORE II is used. CONCLUSIONS: Spanish cardiac surgical patients
      have a high-risk profile. Areas under the ROC curve show good discrimination for
      both models. Predicted mortality using EuroSCORE II more closely matches actual
      mortality than that predicted by the original EuroSCORE. Both models show
      statistically significant differences from the actual mortality rate, with
      EuroSCORE overpredicting and EuroSCORE II underpredicting mortality. The funnel
      plot illustrates risk-adjusted mortality clearly out of boundaries when EuroSCORE
      is used, and near underprediction when the reference is EuroSCORE II.

PMID- 25762398
TI  - An adolescent in acute respiratory distress with giant pulmonary arterio-venous
      malformation.

PMID- 25762399
TI  - Is Ross operation in neonates and infants justified? Aortic valve repair may
      postpone Ross operation.

PMID- 25762400
TI  - Negative prognostic influence of micropapillary pattern in stage IA lung
      adenocarcinoma.
AB  - OBJECTIVES: There is uncertainty as to which factors determine the aggressiveness
      of lung adenocarcinoma with a micropapillary pattern (MPP). The present study
      aimed to clarify the influence of a MPP on the malignant aggressiveness of
      clinical stage IA lung adenocarcinoma. METHODS: We retrospectively examined 347
      consecutive patients with clinical stage IA lung adenocarcinoma who underwent
      complete resection. We defined MPP-positive as accounting for >=5% of the entire
      tumour. RESULTS: Forty-eight (14%) and 299 (86%) patients were MPP-positive and
      negative, respectively. Lymphatic (P = 0.003) and vessel (P = 0.029) invasion as
      well as lymph node metastasis (P = 0.002) were more frequent in the MPP-positive
      than negative group. Five-year disease-free survival (DFS) rates were
      significantly lower in the MPP-positive than negative group (69.7 vs 89.3%, P <
      0.001). Multivariate analysis for DFS showed that MPP (P = 0.048), lymphatic
      invasion (P = 0.003) and vessel invasion (P = 0.002) were independent poor
      prognostic factors. In addition, higher proportions (<5%, 5-30% and >=30%) of MPP
      were associated with a poorer prognosis (89.3, 76.0, and 48.1%, respectively; P <
      0.001). The prognosis of patients with MPP-positive tumours and negative tumours
      harbouring lepidic and solid predominant growth patents did not differ (100 vs
      96.8%, P = 0.564; 66.7 vs 62.5%, P = 0.791, respectively). On the other hand, the
      prognosis tended to be poorer for patients with papillary predominant MPP
      positive tumours than for those with negative tumours (62.5 vs 82.5%, P = 0.075).
      CONCLUSIONS: MPP has an effect on tumour malignancy and patients with tumours
      harbouring a higher ratio of MPP or papillary predominant subtypes have worse
      survival.

PMID- 25762402
TI  - Surgical atrial fibrillation ablation and follow-up strategies: minimally
      invasive or maximally effective?

PMID- 25762401
TI  - Efficacy of wound analgesia for controlling post-thoracotomy pain: a randomized
      double-blind study?.
AB  - OBJECTIVES: Continuous wound infusion of local anaesthetics has been successfully
      applied for postoperative pain control in several procedures but, surprisingly,
      it is underused in thoracic surgery. We aimed to investigate the effects of wound
      analgesia associated with systemic patient-controlled analgesia in patients
      undergoing lung cancer resection with muscle-sparing thoracotomy. METHODS: Sixty
      consecutive patients undergoing lung cancer resection via standard muscle-sparing
      thoracotomy were randomized into two groups (wound analgesia and placebo groups).
      Bupivacaine in the wound group and free-saline solution in the placebo group were
      injected using a multiholed catheter connected to an elastomeric pump inserted at
      the end of operation between the pericostal sutures and the serratus muscle and
      removed 48 h after. The inter-group differences were assessed by the following
      criteria: (i) level of cytokines [IL-6, IL-10 and tumour necrosis factor-alpha
      (TNF-alpha)]; (ii) pain on a visual analogue scale at rest and after coughing;
      (iii) recovery of respiratory functions (flow expiratory volume in 1 s % and
      forced vital capacity %) and (iv) narcotic medication consumption at different
      time points of the postoperative course. RESULTS: Five out of a total of 60
      patients were excluded from the final analysis. Thus, the wound and placebo
      groups comprised 27 and 28 patients, respectively. The wound group compared with
      the placebo group had a significant decrease of IL-6 (P < 0.001), IL-10 (P <
      0.001) and TNF-alpha (P < 0.001) blood concentration levels, pain scores at rest
      (P < 0.001) and after coughing (P = 0.01), and a reduction of additional morphine
      intake (P = 0.03) and Ketorolac (P = 0.01) during the entire postoperative
      course. The recovery of the flow expiratory volume in one second % (P = 0.01) and
      the forced vital capacity % (P = 0.02) was also better in the wound than in the
      placebo group. CONCLUSIONS: Our data prove that wound analgesia is an effective,
      easy and safe procedure. It significantly reduces systemic inflammatory markers,
      pain scores and opioid intake; and accelerates the recovery of respiratory
      function. Catheter placement does not require particular manoeuvres by the
      surgeon nor does the elastomeric pump need any adjustment or care by physicians
      or nurses.

PMID- 25762403
TI  - Butterfly pollination in Pteroglossa (Orchidaceae, Orchidoideae): a comparative
      study on the reproductive biology of two species of a Neotropical genus of
      Spiranthinae.
AB  - Spiranthinae orchids are known for being self-compatible and offering nectar as a
      reward. Although data on their pollinators are scarce, members of this tribe are
      mostly pollinated by bees, hummingbirds and moths. Some of them even reproduce
      through facultative self-pollination. Nothing is known about the pollinators and
      reproduction system in Pteroglossa. Based on records on flowering phenology,
      floral morphology, reward production, pollinators and breeding system, this paper
      aims to study the reproductive biology of two Pteroglossa spp. Both species offer
      nectar as a resource and are pollinated exclusively by diurnal Lepidoptera at the
      studied areas. Nectar is produced by two glandular nectaries, and is stored in a
      spur. Pollinaria possess a ventrally adhesive viscidium that is deposited on the
      basal portion of butterfly proboscides. Both species are self-compatible but
      pollinator-dependent. The reproductive success is low when compared to other
      Spiranthinae. Although no evident mechanical barrier to avoid self-pollination or
      geitonogamy was identified, the erratic behavior of the butterflies, with their
      infrequent visits to only one flower per inflorescence, contributes to an
      increased fruit set produced through cross-pollination. The presence of ventrally
      adhesive viscidia in Spiranthinae is responsible for greater pollinator diversity
      when compared to bee-pollinated Goodyerinae with dorsally adhesive viscidia,
      adapted to attach to bee mouthparts. 

PMID- 25762404
TI  - Measurement of psychosine in dried blood spots--a possible improvement to newborn
      screening programs for Krabbe disease.
AB  - BACKGROUND: Newborn screening (NBS) for Krabbe disease (KD) in New York and
      Missouri is conducted by measuring galactocerebrosidase (GALC) activity using
      tandem mass spectrometry (MS/MS). These NBS efforts have shown that the incidence
      of KD is unexpectedly low (1:400,000) while many individuals (ca. 1:6000) with
      reduced GALC activity and genotypes of uncertain significance are detected and
      subjected to follow up testing. Psychosine (PSY) is a putative marker of KD
      progression and can be measured in dried blood spots (DBS). We sought to
      determine the role that PSY levels play in NBS for KD, follow up, and treatment
      monitoring. METHODS: PSY was eluted from DBS with methanol containing N,N
      dimethyl-D-erythro-sphingosine as internal standard (IS). Liquid chromatography
      MS/MS was conducted over 17 minutes in the multiple reaction monitoring positive
      mode to follow the precursor to product species transitions for PSY and IS.
      Separation of the structural isomers PSY and glucosylsphingosine was accomplished
      by hydrophilic interaction liquid chromatography. RESULTS: Pre-analytical and
      analytical factors were studied and revealed satisfactory results. PSY was also
      measured in DBS collected from controls (range: <8 nmol/L, N = 220), KD patients
      at various disease stages (range: 8-112, N = 26), and GALC mutation carriers
      (range: <15 nmol/L, N = 18). CONCLUSIONS: PSY measurement in DBS could serve as a
      2nd tier assay in NBS for KD, simplify and reduce the cost of follow up
      protocols, help determine disease progression, and be used to monitor KD patients
      following hematopoietic stem cell transplantation. However, additional
      chronological measurements of PSY in KD patients are required to confirm these
      possibilities.

PMID- 25762405
TI  - Homogentisate 1,2 dioxygenase is expressed in brain: implications in
      alkaptonuria.
AB  - Alkaptonuria is an ultra-rare autosomal recessive disease developed from the lack
      of homogentisate 1,2-dioxygenase (HGD) activity, causing an accumulation in
      connective tissues of homogentisic acid (HGA) and its oxidized derivatives in
      polymerized form. The deposition of ochronotic pigment has been so far attributed
      to homogentisic acid produced by the liver, circulating in the blood, and
      accumulating locally. In the present paper, we report the expression of HGD in
      the brain. Mouse and human brain tissues were positively tested for HGD gene
      expression by western blotting. Furthermore, HGD expression was confirmed in
      human neuronal cells that also revealed the presence of six HGD molecular
      species. Moreover, once cultured in HGA excess, human neuronal cells produced
      ochronotic pigment and amyloid. Our findings indicate that alkaptonuric brain
      cells produce the ochronotic pigment in loco and this may contribute to induction
      of neurological complications. 

PMID- 25762406
TI  - Newborn screening for homocystinurias and methylation disorders: systematic
      review and proposed guidelines.
AB  - Newborn screening (NBS) is justified if early intervention is effective in a
      disorder generally not detected early in life on a clinical basis, and if
      sensitive and specific biochemical markers exist. Experience with NBS for
      homocystinurias and methylation disorders is limited. However, there is robust
      evidence for the success of early treatment with diet, betaine and/or pyridoxine
      for CBS deficiency and good evidence for the success of early betaine treatment
      in severe MTHFR deficiency. These conditions can be screened in dried blood spots
      by determining methionine (Met), methionine-to-phenylanine (Met/Phe) ratio, and
      total homocysteine (tHcy) as a second tier marker. Therefore, we recommend NBS
      for cystathionine beta-synthase and severe MTHFR deficiency. Weaker evidence is
      available for the disorders of intracellular cobalamin metabolism. Early
      treatment is clearly of advantage for patients with the late-onset cblC defect.
      In the early-onset type, survival and non-neurological symptoms improve but the
      effect on neurocognitive development is uncertain. The cblC defect can be
      screened by measuring propionylcarnitine, propionylcarnitine-to-acetylcarnitine
      ratio combined with the second tier markers methylmalonic acid and tHcy. For the
      cblE and cblG defects, evidence for the benefit of early treatment is weaker; and
      data on performance of Met, Met/Phe and tHcy even more limited. Individuals
      homozygous or compound heterozygous for MAT1A mutations may benefit from
      detection by NBS using Met, which on the other hand also detects asymptomatic
      heterozygotes. Clinical and laboratory data is insufficient to develop any
      recommendation on NBS for the cblD, cblF, cblJ defects, glycineN
      methyltransferase-, S-adenosylhomocysteinehydrolase- and adenosine kinase
      deficiency. 

PMID- 25762407
TI  - Primate immune responses to HIV-1 Env formulated in the saponin-based adjuvant
      AbISCO-100 in the presence or absence of TLR9 co-stimulation.
AB  - Protein-based vaccines require adjuvants to achieve optimal responses. Toll-like
      receptor (TLR) 9 agonists were previously shown to improve responses to protein
      based vaccines, such as the Hepatitis B virus vaccine formulated in alum. Here,
      we used CpG-C together with the clinically relevant saponin-based adjuvant AbISCO
      100/Matrix-M (AbISCO), to assess if TLR9 co-stimulation would quantitatively or
      qualitatively modulate HIV-1 envelope glycoprotein (Env)-specific B and T cell
      responses in rhesus macaques. The macaques were inoculated with soluble Env
      trimers in AbISCO, with or without the addition of CpG-C, using an interval
      similar to the Hepatitis B virus vaccine. Following a comprehensive evaluation of
      antigen-specific responses in multiple immune compartments, we show that the Env
      specific circulating IgG, memory B cells and plasma cells displayed similar
      kinetics and magnitude in the presence or absence of CpG-C and that there was no
      apparent difference between the two groups in the elicited HIV-1 neutralizing
      antibody titers or antigen-specific CD4+ T cell responses. Importantly, the
      control of SHIV viremia was significantly improved in animals from both Env
      immunized groups relative to adjuvant alone controls, demonstrating the potential
      of AbISCO to act as a stand-alone adjuvant for Env-based vaccines. 

PMID- 25762408
TI  - High- and low-grade glioma differentiation: the role of percentage signal
      recovery evaluation in MR dynamic susceptibility contrast imaging.
AB  - PURPOSE: Evaluation of cerebral blood volume (CBV) with magnetic resonance (MR)
      imaging can differentiate low-grade from high-grade gliomas. The percentage of
      signal recovery (PSR) in the venous phase of perfusion curves is inversely
      proportional to blood-brain barrier (BBB) permeability. Since even BBB
      permeability relates to glioma malignancy grade, we carried out a comparative
      evaluation between CBV and PSR to characterise cerebral gliomas. MATERIALS AND
      METHODS: Forty-nine patients with cerebral gliomas were studied with MR perfusion
      imaging. In all tumours, both maximum CBV and minimum PSR were calculated. The
      difference between the CBV and PSR mean values among the low-grade and high-grade
      gliomas was assessed using statistical methods. We also examined whether there
      was an additional difference between low-grade and grade III gliomas. Finally,
      CBV and PSR diagnostic sensitivity and specificity in identifying low-grade
      gliomas compared to all gliomas and low-grade gliomas compared to all gliomas
      excluding glioblastomas was assessed. RESULTS: A significant difference between
      low-grade and high-grade gliomas with both CBV and PSR was demonstrated.
      Conversely, there was a significant difference between low-grade and grade III
      gliomas only with PSR, while CBV did not show significant difference. Finally,
      superior sensitivity and specificity of PSR compared to CBV in identifying low
      grade gliomas was demonstrated both compared to all gliomas and all gliomas
      excluding glioblastomas. CONCLUSION: The PSR evaluation proved better than CBV
      for determining the grade of brain and is therefore a useful tool to be
      considered in the MR evaluation of gliomas.

PMID- 25762409
TI  - Allostery through protein-induced DNA bubbles.
AB  - Allostery through DNA is increasingly recognized as an important modulator of DNA
      functions. Here, we show that the coalescence of protein-induced DNA bubbles can
      mediate allosteric interactions that drive protein aggregation. We propose that
      such allostery may regulate DNA's flexibility and the assembly of the
      transcription machinery. Mitochondrial transcription factor A (TFAM), a dual
      function protein involved in mitochondrial DNA (mtDNA) packaging and
      transcription initiation, is an ideal candidate to test such a hypothesis owing
      to its ability to locally unwind the double helix. Numerical simulations
      demonstrate that the coalescence of TFAM-induced bubbles can explain
      experimentally observed TFAM oligomerization. The resulting melted DNA segment,
      approximately 10 base pairs long, around the joints of the oligomers act as
      flexible hinges, which explains the efficiency of TFAM in compacting DNA. Since
      mitochondrial polymerase (mitoRNAP) is involved in melting the transcription
      bubble, TFAM may use the same allosteric interaction to both recruit mitoRNAP and
      initiate transcription. 

PMID- 25762410
TI  - Spin-dependent charge transfer state design rules in organic photovoltaics.
AB  - Charge transfer states play a crucial role in organic photovoltaics, mediating
      both photocurrent generation and recombination losses. In this work, we examine
      recombination losses as a function of the electron-hole spacing in fluorescent
      charge transfer states, including direct monitoring of both singlet and triplet
      charge transfer state dynamics. Here we demonstrate that large donor-acceptor
      separations minimize back transfer from the charge transfer state to a low-lying
      triplet exciton 'drain' or the ground state by utilizing external pressure to
      modulate molecular spacing. The triplet drain quenches triplet charge transfer
      states that would otherwise be spin protected against recombination, and switches
      the most efficient origin of the photocurrent from triplet to singlet charge
      transfer states. Future organic solar cell designs should focus on raising the
      energy of triplet excitons to better utilize triplet charge transfer mediated
      photocurrent generation or increasing the donor-acceptor spacing to minimize
      recombination losses. 

PMID- 25762411
TI  - Vitamin E intake, alpha-tocopherol levels and pulmonary function in children and
      adolescents with cystic fibrosis.
AB  - Pancreatic insufficiency cystic fibrosis (CF) patients receive vitamin E
      supplementation according to CF-specific recommendations in order to prevent
      deficiencies. It has been suggested that higher serum alpha-tocopherol levels
      could have protective effects on pulmonary function (PF) in patients with CF.
      Whether current recommendations are indeed optimal for preventing deficiency and
      whether vitamin E has therapeutic benefits are subjects of debate. Therefore, we
      studied vitamin E intake as well as the long-term effects of vitamin E intake,
      the coefficient of fat absorption (CFA) and IgG on alpha-tocopherol levels. We
      also examined the long-term effects of serum alpha-tocopherol and serum IgG on
      forced expiratory volume in 1 s expressed as percentage of predicted (FEV1%
      pred.) in paediatric CF patients during a 7-year follow-up period. We found that
      CF patients failed to meet the CF-specific vitamin E recommendations, but serum
      alpha-tocopherol below the 2.5th percentile was found in only twenty-three of the
      1022 measurements (2 %). Furthermore, no clear effect of vitamin E intake or the
      CFA on serum alpha-tocopherol was found (both P>= 0.103). FEV1% pred. was
      longitudinally inversely associated with age (P< 0.001) and serum IgG (P= 0.003),
      but it was not related to serum alpha-tocopherol levels. We concluded that in the
      present large sample of children and adolescents with CF, vitamin E intake was
      lower than recommended, but serum alpha-tocopherol deficiency was rare. We found
      no evidence that higher serum alpha-tocopherol levels had protective effects on
      PF. Adjustment of the recommendations to the real-life intake of these patients
      may be considered.

PMID- 25762412
TI  - Investigating the role of CH2 radicals in the HACA mechanism.
AB  - Detailed mechanisms of PAH growth involving methylene (CH2) were studied using
      accurate ab initio density functional theory B3LYP/6-311+G(d,p) calculations, as
      well as approximate QCISD(T,full)/6-311++G(3df,2pd) calculations. The PAH growth
      can be divided into five essential reaction steps, namely, addition C2H2 ->
      intramolecular hydrogen migration -> addition CH2 -> cyclization -> H
      elimination. The aliphatic species of indene and 1H-phenalene are found in the
      pathways of PAH growth, which is in accord with the experimental results that
      reveal the formation of aliphatic species in flames. It was found that the
      simultaneous removal of two H atoms in one reaction step is feasible in PAH
      evolution, and this can reasonably interpret the absence of a H atom in the post
      flame region. The corresponding rate coefficients at 1 atm were evaluated by
      using TST and RRKM theory by solving the master equations in the temperature
      range of 500-2500 K. The calculated branching ratios suggest that the pathways
      involving CH2 are competitive in PAH growth.

PMID- 25762413
TI  - The emerging roles of long noncoding RNAs in common cardiovascular diseases.
AB  - Long noncoding RNAs (lncRNAs) are defined as noncoding RNAs that are longer than
      ~200 nucleotides and lack protein-encoding capacity. It has been shown that
      lncRNAs are involved in multiple human diseases by regulating gene expression at
      various levels. However, studies of lncRNAs in the cardiovascular system are
      still in their infancy. A growing body of evidence suggests that lncRNAs are also
      involved in common cardiovascular diseases, including cardiac development,
      atherosclerosis, myocardial infarction, heart failure, hypertension and
      aneurysms. In this review, we summarize the current understanding of lncRNAs in
      common cardiovascular diseases in an effort to better elucidate the molecular
      mechanism of cardiovascular diseases and provide a basis for exploring new
      therapeutic targets in those diseases. 

PMID- 25762414
TI  - Association between the markers of metabolic acid load and higher all-cause and
      cardiovascular mortality in a general population with preserved renal function.
AB  - Although metabolic acid load has been associated with many well-known risk
      factors for mortality, its clinical implications are not yet clear. To evaluate
      the association between biomarkers of metabolic acid load, such as serum
      bicarbonate, serum anion gap and urine pH and mortality, we analyzed the health
      records of 31,590 adults who underwent a health screening between January 2001
      and December 2010 and had an estimated glomerular filtration rate ?60 ml min(-1)
      per 1.73 m2. Urine pH was measured by a dipstick test performed on fast morning
      urine sample and categorized as acidic (urine pH ?5.5), neutral and alkaline
      (urine pH ?8.0). Using the Cox proportional hazard model, the adjusted hazard
      ratio (aHR) of all-cause mortality of the lowest quartile of serum bicarbonate
      was 1.460 (95% confidence interval (CI) 1.068-1.995) compared with the highest
      quartile, after a median follow-up of 93 months. The aHRs of cardiovascular and
      cancer mortality of the lowest quartile of serum bicarbonate were 2.647 (95% CI
      1.148-6.103) and 1.604 (95% CI 1.024-2.513), respectively, compared with the
      highest quartile. Acidic and neutral urine pH were significantly associated with
      a higher all-cause mortality (aHR 2.550, 95% CI 1.316-4.935; aHR 2.376 95% CI
      1.254-4.501, respectively), compared with an alkaline urine pH. In conclusion,
      higher metabolic acid load was associated with an increased all-cause and
      cardiovascular mortality in a healthy population. The association between
      metabolic acid load and mortality and the causality of the relationship need to
      be confirmed.

PMID- 25762416
TI  - Short and sweet.

PMID- 25762415
TI  - The necessity and effectiveness of mineralocorticoid receptor antagonist in the
      treatment of diabetic nephropathy.
AB  - Diabetes mellitus is a major cause of chronic kidney disease (CKD), and diabetic
      nephropathy is the most common primary disease necessitating dialysis treatment
      in the world including Japan. Major guidelines for treatment of hypertension in
      Japan, the United States and Europe recommend the use of angiotensin-converting
      enzyme inhibitors and angiotensin-receptor blockers, which suppress the renin
      angiotensin system (RAS), as the antihypertensive drugs of first choice in
      patients with coexisting diabetes. However, even with the administration of RAS
      inhibitors, failure to achieve adequate anti-albuminuric, renoprotective effects
      and a reduction in cardiovascular events has also been reported. Inadequate
      blockade of aldosterone may be one of the reasons why long-term administration of
      RAS inhibitors may not be sufficiently effective in patients with diabetic
      nephropathy. This review focuses on treatment in diabetic nephropathy and
      discusses the significance of aldosterone blockade. In pre-nephropathy without
      overt nephropathy, a mineralocorticoid receptor antagonist can be used to enhance
      the blood pressure-lowering effects of RAS inhibitors, improve insulin resistance
      and prevent clinical progression of nephropathy. In CKD categories A2 and A3, the
      addition of a mineralocorticoid receptor antagonist to an RAS inhibitor can help
      to maintain 'long-term' antiproteinuric and anti-albuminuric effects. However, in
      category G3a and higher, sufficient attention must be paid to hyperkalemia.
      Mineralocorticoid receptor antagonists are not currently recommended as standard
      treatment in diabetic nephropathy. However, many studies have shown promise of
      better renoprotective effects if mineralocorticoid receptor antagonists are
      appropriately used. 

PMID- 25762417
TI  - Whole-Exome Enrichment with the Agilent SureSelect Human All Exon Platform.
AB  - There are multiple platforms available for whole-exome enrichment and sequencing
      (WES). This protocol is based on the Agilent SureSelect Human All Exon platform,
      which targets ~50 Mb of the human exonic regions. The SureSelect system uses ~120
      base RNA probes to capture known coding DNA sequences (CDS) from the NCBI
      Consensus CDS Database as well as other major RNA coding sequence databases, such
      as Sanger miRBase. The protocol can be performed at the benchside without the
      need for automation, and the resulting library can be used for targeted next
      generation sequencing on an Illumina HiSeq 2000 sequencer. 

PMID- 25762418
TI  - Whole-Exome Enrichment with the Illumina TruSeq Exome Enrichment Platform.
AB  - Multiple platforms are available for whole-exome enrichment and sequencing (WES).
      This protocol is based on the Illumina TruSeq Exome Enrichment platform, which
      captures ~62 Mb of the human exonic regions using 95-base DNA probes. In addition
      to covering the RefSeq and Ensembl coding sequences, the enriched sequences also
      include ~28 Mb of RefSeq untranslated regions (UTR). The protocol can be
      performed at the benchside without the need for automation, and the resulting
      library can be used for targeted next-generation sequencing on an Illumina HiSeq
      2000 sequencer. 

PMID- 25762419
TI  - Whole-Exome Enrichment with the Roche NimbleGen SeqCap EZ Exome Library SR
      Platform.
AB  - Multiple platforms are available for whole-exome enrichment and sequencing (WES).
      This protocol is based on the Roche NimbleGen SeqCap EZ Exome Library SR
      platform, which enriches for ~44 Mb of the human exonic regions. The SeqCap
      system uses 55- to 105-base DNA probes to capture known coding DNA sequences
      (CDS) from the NCBI Consensus CDS Database, RefSeq, and Sanger miRBase. The
      protocol can be performed at the benchside without the need for automation, and
      the resulting library can be used for targeted next-generation sequencing on an
      Illumina HiSeq 2000 sequencer. 

PMID- 25762420
TI  - Using the ENCODE Resource for Functional Annotation of Genetic Variants.
AB  - This article illustrates the use of the Encyclopedia of DNA Elements (ENCODE)
      resource to generate or refine hypotheses from genomic data on disease and other
      phenotypic traits. First, the goals and history of ENCODE and related epigenomics
      projects are reviewed. Second, the rationale for ENCODE and the major data types
      used by ENCODE are briefly described, as are some standard heuristics for their
      interpretation. Third, the use of the ENCODE resource is examined. Standard use
      cases for ENCODE, accessing the ENCODE resource, and accessing data from related
      projects are discussed. Although the focus of this article is the use of ENCODE
      data, some of the same approaches can be used with data from other projects. 

PMID- 25762421
TI  - Macrophage migration inhibitory factor as a potential predictor for requirement
      of renal replacement therapy after orthotopic liver transplantation.
AB  - Acute kidney injury (AKI) after orthotopic liver transplantation (OLT) is
      associated with a poor clinical outcome. Because there is no specific treatment
      for postoperative AKI, early recognition and prevention are fundamental
      therapeutic approaches. Concentrations of the proinflammatory cytokine macrophage
      migration inhibitory factor (MIF) are elevated in patients with kidney disease.
      We hypothesized that plasma MIF concentrations would be greater in patients
      developing AKI after OLT compared with patients with normal kidney function.
      Twenty-eight patients undergoing OLT were included in the study. Kidney injury
      was classified according to AKI network criteria. Fifteen patients (54%)
      developed severe AKI after OLT, 11 (39%) requiring renal replacement therapy
      (RRT). On the first postoperative day, patients with severe AKI had greater
      plasma MIF concentrations (237 +/- 123 ng/mL) than patients without AKI (95 +/-
      63 ng/mL; P < 0.001). The area under the receiver operating characteristic (ROC)
      curve for predicting severe AKI was 0.87 [95% confidence interval (CI), 0.69
      0.97] for plasma MIF, 0.61 (95% CI, 0.40-0.79) for serum creatinine (sCr), and
      0.90 (95% CI, 0.72-0.98) for delta serum creatinine (DeltasCr). Plasma MIF (P =
      0.02) and DeltasCr (P = 0.01) yielded a better predictive value than sCr for the
      development of severe AKI. Furthermore, the area under the ROC curve to predict
      the requirement of RRT was 0.87 (95% CI, 0.68-0.96) for plasma MIF, 0.65 (95% CI,
      0.44-0.82) for sCr, and 0.72 (95% CI, 0.52-0.88) for DeltasCr. Plasma MIF had a
      better predictive value than sCr for the requirement of RRT (P = 0.02). In
      conclusion, postoperative plasma MIF concentrations were elevated in patients who
      developed severe AKI after OLT. Furthermore, plasma MIF concentrations showed a
      good prognostic value for identifying patients developing severe AKI or requiring
      postoperative RRT after OLT.

PMID- 25762423
TI  - A classification system for large reservoirs of the contiguous United States.
AB  - Degradation of reservoir fish habitat has become a serious concern. Habitat
      issues-such as sedimentation, excessive nutrient loadings, and lack of submerged
      structure-may emerge and worsen over time and are accompanied by undesirable
      shifts in the fish community and fisheries. To prioritize habitat rehabilitation
      efforts in reservoirs, we developed a classification system for large reservoirs
      in the contiguous U.S. We used a four-step classification approach based on over
      50 variables descriptive of habitat impairment in a sample of almost 1300
      reservoirs. To account for the broad geographic heterogeneity in climate and
      landscape, reservoirs were assigned to a spatial framework relevant to aquatic
      resources, selected based on how well it recognized regional differences in fish
      habitat. To account for differences among reservoirs within geographical regions,
      we used cluster analysis to identify classes of reservoirs with similar
      characteristics. Classes were compared regarding habitat impairment, the fish
      community, the recreational fishery, and other variables from an external dataset
      to seek support for the classification system. A method for classifying new
      reservoirs not included in the original sample was also developed. The resulting
      classification system identified nine geographical regions distributed throughout
      the contiguous U.S. and 24 reservoir classes within the nine regions. The system
      can serve as the framework for a reservoir assessment mechanism. Our approach may
      be applicable elsewhere a broad-scale dataset is not available and needs to be
      obtained quickly and inexpensively, whether in regards to fish habitat or other
      environmental information needs. 

PMID- 25762422
TI  - Mouse forepaw lumbrical muscles are resistant to age-related declines in force
      production.
AB  - A progressive loss of skeletal muscle mass and force generating capacity occurs
      with aging. Mice are commonly used in the study of aging-associated changes in
      muscle size and strength, with most models of aging demonstrating 15-35%
      reductions in muscle mass, cross-sectional area (CSA), maximum isometric force
      production (Po) and specific force (sPo), which is Po/CSA. The lumbrical muscle
      of the mouse forepaw is exceptionally small, with corresponding short diffusion
      distances that make it ideal for in vitro pharmacological studies and
      measurements of contractile properties. However, the aging-associated changes in
      lumbrical function have not previously been reported. To address this, we tested
      the hypothesis that compared to adult (12month old) mice, the forepaw lumbrical
      muscles of old (30month old) mice exhibit aging-related declines in size and
      force production similar to those observed in larger limb muscles. We found that
      the forepaw lumbricals were composed exclusively of fibers with type II myosin
      heavy chain isoforms, and that the muscles accumulated connective tissue with
      aging. There were no differences in the number of fibers per whole-muscle cross
      section or in muscle fiber CSA. The whole muscle CSA in old mice was increased by
      17%, but the total CSA of all muscle fibers in a whole-muscle cross-section was
      not different. No difference in Po was observed, and while sPo normalized to
      total muscle CSA was decreased in old mice by 22%, normalizing Po by the total
      muscle fiber CSA resulted in no difference in sPo. Combined, these results
      indicate that forepaw lumbrical muscles from 30month old mice are largely
      protected from the aging-associated declines in size and force production that
      are typically observed in larger limb muscles. 

PMID- 25762424
TI  - Seasonal nitrate algorithms for nitrate retrieval using OCEANSAT-2 and MODIS-AQUA
      satellite data.
AB  - In situ datasets of nitrate, sea surface temperature (SST), and chlorophyll a
      (chl a) collected during the monthly coastal samplings and organized cruises
      along the Tamilnadu and Andhra Pradesh coast between 2009 and 2013 were used to
      develop seasonal nitrate algorithms. The nitrate algorithms have been built up
      based on the three-dimensional regressions between SST, chl a, and nitrate in
      situ data using linear, Gaussian, Lorentzian, and paraboloid function fittings.
      Among these four functions, paraboloid was found to be better with the highest co
      efficient of determination (postmonsoon: R2=0.711, n=357; summer: R2=0.635,
      n=302; premonsoon: R2=0.829, n=249; and monsoon: R2=0.692, n=272) for all
      seasons. Based on these fittings, seasonal nitrate images were generated using
      the concurrent satellite data of SST from Moderate Resolution Imaging
      Spectroradiometer (MODIS) and chlorophyll (chl) from Ocean Color Monitor (OCM-2)
      and MODIS. The best retrieval of modeled nitrate (R2=0.527, root mean square
      error (RMSE)=3.72, and mean normalized bias (MNB)=0.821) was observed for the
      postmonsoon season due to the better retrieval of both SST MODIS (28 February
      2012, R2=0.651, RMSE=2.037, and MNB=0.068) and chl OCM-2 (R2=0.534, RMSE=0.317,
      and MNB=0.27). Present results confirm that the chl OCM-2 and SST MODIS retrieve
      nitrate well than the MODIS-derived chl and SST largely due to the better
      retrieval of chl by OCM-2 than MODIS.

PMID- 25762425
TI  - Distribution and accumulation of polycyclic aromatic hydrocarbons (PAHs) in the
      food web of Nansi Lake, China.
AB  - The concentrations of polycyclic aromatic hydrocarbons (PAHs) were analyzed in
      water, sediment, and biota (aquatic plant, shrimp, and fish) of Nansi Lake by gas
      chromatography-mass spectrometry (GC-MS). The concentrations of total PAHs were
      27.54-55.04 ng L(-1) in water, 80.31-639.23 ng g(-1) dry weight (dw) in
      sediments, 20.92-192.78 ng g(-1) dw in aquatic plants, and 67.3-533.9 ng g(-1) dw
      in fish and shrimp muscles. The ratios of phenanthrene to anthracene (Ph/An),
      fluoranthene to pyrene (Flu/Pyr), and low molecular weight to high molecular
      weight (LMW/HMW) in sediment indicated that the sources of the PAHs were a
      mixture of pyrolytic and petrogenic contamination at most sampling sites in Nansi
      Lake. The composition profile of PAHs in plants was similar to that in water and
      animals with 2-3 ring PAHs being dominant. The 4-6 ring PAHs were the dominant
      PAH compounds in sediment. There is a positive correlation between sediment and
      aquatic plants, but their PAH composition profiles were different, implying that
      aquatic plant absorption of PAHs from sediment is selective and the accumulation
      of PAHs in aquatic plants is different. The concentration of PAHs in fish showed
      a positive correlation with plants, reflecting that the PAHs in fish are mainly
      absorbed from aquatic plants rather than directly from the water. Bioaccumulation
      of LMW PAHs in aquatic biota was higher than HMW PAHs. The biota-sediment
      accumulation factor (BSAF) values of total PAHs in the plants Potamogeton lucens
      Linn and Ceratophyllum demersum Linn were higher than that in most animals. The
      BSAF values of total PAHs in animals were in the following order: Cyprinus
      carpio>Macrobrachium nipponense>Carassius auratus>Channa argus. There was no
      significant relationship between PAH bioaccumulation and trophic levels in Nansi
      Lake. Risk assessment of PAHs in water, sediment, and animals indicated that the
      water environment of Nansi Lake is safe at present. It is worthwhile to note that
      benzo [a] anthracene (BaA), benzo [a] pyrene (BaP), indeno [1,2,3-cd] pyrene
      (InP), dibenz [a, h] anthracene (DBA), and benzo [ghi] perylene (BghiP) were
      detected in sediment, plants, and animals at all sampling sites, and they have
      potential carcinogenicity to the organisms of Nansi Lake.

PMID- 25762426
TI  - Relaxation and guided imagery do not reduce stress, pain and unpleasantness for
      11- to 12-year-old girls during vaccinations.
AB  - AIM: Relaxation and guided imagery is a distraction technique known to reduce
      discomfort during paediatric medical procedures. We examined whether its use
      decreased the stress experienced by 11- to 12-year-old girls receiving the human
      papilloma virus vaccination, as well as the intensity and unpleasantness of any
      pain. METHODS: A randomised crossover trial was conducted with 37 girls. During
      the first vaccination, each girl was randomised to receive either relaxation and
      guided imagery or standard care. They then received the other form of care during
      the second vaccination. Salivary cortisol was measured before each vaccination,
      and 30 minutes after it was administered. The girls reported pain intensity and
      pain unpleasantness before and directly after each vaccination and stress after
      each vaccination. RESULTS: On a group level, relaxation and guided imagery did
      not decrease cortisol levels, self-reported stress, pain intensity and pain
      unpleasantness. Salivary cortisol levels decreased significantly in both groups
      during the second vaccination. CONCLUSION: Relaxation and guided imagery did not
      prove beneficial during the vaccination of 11- to 12-year-old girls and is not
      recommended as a regular nursing intervention. However, further research is
      needed into effective techniques to help children who experience pain
      unpleasantness in connection with needle procedures.

PMID- 25762427
TI  - Configural integration of temporal and contextual information in rats: Automated
      measurement in appetitive and aversive preparations.
AB  - Two experiments investigated the capacity of rats to learn configural
      discriminations requiring integration of contextual (where) with temporal (when)
      information. In Experiment 1, during morning training sessions, food was
      delivered in context A and not in context B, whereas during afternoon sessions
      food was delivered in context B and not in context A. Rats acquired this
      discrimination over the course of 20 days. Experiment 2 employed a directly
      analogous aversive conditioning procedure in which footshock served in place of
      food. This procedure allowed the acquisition of the discrimination to be assessed
      through changes in activity to the contextual + temporal configurations (i.e.,
      inactivity or freezing) and modulation of the immediate impact of footshock
      presentations (i.e., post-shock activity bursts). Both measures provided evidence
      of configural learning over the course of 12 days, with a final test showing that
      the presentation of footshock resulted in more post-shock activity in the
      nonreinforced than reinforced configurations. These behavioral effects reveal
      important parallels between (i) configural discrimination learning involving
      components allied to episodic memory and (ii) simple conditioning.

PMID- 25762428
TI  - Using the reassignment procedure to test object representation in pigeons and
      people.
AB  - In four experiments, we evaluated Lea's (1984) reassignment procedure for
      studying object representation in pigeons (Experiments 1-3) and humans
      (Experiment 4). In the initial phase of Experiment 1, pigeons were taught to make
      discriminative button responses to five views of each of four objects. Using the
      same set of buttons in the second phase, one view of each object was trained to a
      different button. In the final phase, the four views that had been withheld in
      the second stage were shown. In Experiment 2, pigeons were initially trained just
      like the birds in Experiment 1. Then, one view of each object was reassigned to a
      different button, now using a new set of four response buttons. In Experiment 3,
      the reassignment paradigm was again tested using the number of pecks to bind
      together different views of the same object. Across all three experiments,
      pigeons showed statistically significant generalization of the new response to
      the non-reassigned views, but such responding was well below that to the
      reassigned view. In Experiment 4, human participants were studied using the same
      stimuli and task as the pigeons in Experiment 1. People did strongly generalize
      the new response to the non-reassigned views. These results indicate that humans,
      but not pigeons, can employ a unified object representation that they can
      flexibly map to different responses under the reassignment procedure. 

PMID- 25762429
TI  - Motivation and Contingency Management Treatments for Substance Use Disorders.
AB  - Contingency management (CM) is a highly efficacious psychosocial treatment for
      substance use disorders based on the principles of behavioral analysis. CM
      involves delivering a tangible positive reinforcer following objective evidence
      of submission of a drug-negative urine sample. Although CM interventions
      primarily involve applying extrinsic rewards, a patient's intrinsic motivation to
      change substance use behavior may also be impacted by CM. This chapter provides
      an introduction to CM interventions for substance use disorders and examines the
      impact of CM on intrinsic motivation . It also addresses applications of this
      intervention to other conditions and patient populations. 

PMID- 25762430
TI  - Effects of increasing nurse staffing on missed nursing care.
AB  - BACKGROUND: Inadequate nurse staffing has been reported to lead nurses to omit
      required nursing care. In South Korea, to reduce informal caregiving by patient
      families and sitters and to improve the quality of nursing care, a public
      hospital operated by the Seoul Metropolitan Government has implemented a policy
      of increasing nurse staffing from 17 patients per registered nurse to 7 patients
      per registered nurse in 4 out of 13 general nursing units since January 2013.
      AIM: The study aims to compare missed nursing care (omission of required care) in
      high-staffing (7 patients per nurse) units vs. low-staffing (17 patients per
      nurse) units to examine the effects of nurse staffing on missed care. METHODS: A
      nurse survey conducted in July 2013 targeted all staff nurses in all four high
      staffing and all nine low-staffing units; 115 nurses in the high-staffing units
      (response rate = 94.3%) and 117 nurses in the low-staffing units (response rate =
      88.6%) participated. Missed nursing care was measured using the MISSCARE survey
      that included 24 nursing care elements. Nurses were asked how frequently they had
      missed each element on a 4-point scale from 'rarely' to 'always'. RESULTS:
      Overall, nurses working in high-staffing units had a significantly lower mean
      score of missed care than those in low-staffing units. Seven out of 24 nursing
      care elements were missed significantly less often in high-staffing (vs. low
      staffing) units: turning, mouth care, bathing/skin care, patient assessments in
      each shift, assistance with toileting, feeding and setting up meals. CONCLUSION:
      The findings suggest that increasing nurse staffing is associated with a decrease
      in missed care. Less omission of required nursing care is expected to improve
      nursing surveillance and patient outcomes, such as patient falls, pressure ulcers
      and pneumonia. IMPLICATIONS FOR NURSING AND HEALTH POLICY: Adequate nurse
      staffing should be ensured to reduce unmet nursing needs and improve patient
      outcomes.

PMID- 25762431
TI  - Efficacious redox-responsive gene delivery in serum by ferrocenylated monomeric
      and dimeric cationic cholesterols.
AB  - Herein, we present the design and synthesis of new redox-active monomeric and
      dimeric (gemini) cationic lipids based on ferrocenylated cholesterol derivatives
      for gene delivery. The cationic cholesterols are shown to be transfection
      efficient after being formulated with the neutral helper lipid DOPE in the
      presence of serum (FBS). The redox activity of the resulting co-liposomes and
      their lipoplexes could be regulated using the alkanyl ferrocene moiety attached
      to the ammonium head groups of the cationic cholesterols. Atomic force microscopy
      (AFM), dynamic light scattering (DLS) and zeta potential measurements were
      performed to characterize the co-liposomal aggregates and their complexes with
      pDNA. The transfection efficiency of lipoplexes could be tuned by changing the
      oxidation state of the ferrocene moiety. The gene transfection capability was
      assayed in terms of green fluorescence protein (GFP) expression using pEGFP-C3
      plasmid DNA in three cell lines of different origins, namely Caco-2, HEK293T and
      HeLa, in the presence of serum. The vesicles possessing ferrocene in the reduced
      state induced an efficient transfection, even better than a commercial reagent
      Lipofectamine 2000 (Lipo 2000) as evidenced by flow cytometry and fluorescence
      microscopy. All the co-liposomes containing the oxidized ferrocene displayed
      diminished levels of gene expression. Gene transfection events from the oxidized
      co-liposomes were further potentiated by introducing ascorbic acid (AA) as a
      reducing agent during lipoplex incubation with cells, leading to the resumption
      of transfection activity. Assessment of transfection capability of both reduced
      and oxidized co-liposomes was also undertaken following cellular internalization
      of labelled pDNA using confocal microscopy and flow cytometry. Overall, we
      demonstrate here controlled gene transfection activities using redox-driven,
      transfection efficient cationic monomeric and dimeric cholesterol lipids. Such
      systems could be used in gene delivery applications where transfection needs to
      be performed spatially or temporally. 

PMID- 25762432
TI  - Clinical applications at ultrahigh field (7  T). Where does it make the
      difference?
AB  - Presently, three major MR vendors provide commercial 7-T units for clinical
      research under ethical permission, with the number of operating 7-T systems
      having increased to over 50. This rapid increase indicates the growing interest
      in ultrahigh-field MRI because of improved clinical results with regard to
      morphological as well as functional and metabolic capabilities. As the signal-to
      noise ratio scales linearly with the field strength (B0 ) of the scanner, the
      most obvious application at 7 T is to obtain higher spatial resolution in the
      brain, musculoskeletal system and breast. Of specific clinical interest for neuro
      applications is the cerebral cortex at 7 T, for the detection of changes in
      cortical structure as a sign of early dementia, as well as for the visualization
      of cortical microinfarcts and cortical plaques in multiple sclerosis. In the
      imaging of the hippocampus, even subfields of the internal hippocampal anatomy
      and pathology can be visualized with excellent resolution. The dynamic and static
      blood oxygenation level-dependent contrast increases linearly with the field
      strength, which significantly improves the pre-surgical evaluation of eloquent
      areas before tumor removal. Using susceptibility-weighted imaging, the plaque
      vessel relationship and iron accumulation in multiple sclerosis can be visualized
      for the first time. Multi-nuclear clinical applications, such as sodium imaging
      for the evaluation of repair tissue quality after cartilage transplantation and
      (31) P spectroscopy for the differentiation between non-alcoholic benign liver
      disease and potentially progressive steatohepatitis, are only possible at
      ultrahigh fields. Although neuro- and musculoskeletal imaging have already
      demonstrated the clinical superiority of ultrahigh fields, whole-body clinical
      applications at 7 T are still limited, mainly because of the lack of suitable
      coils. The purpose of this article was therefore to review the clinical studies
      that have been performed thus far at 7 T, compared with 3 T, as well as those
      studies performed at 7 T that cannot be routinely performed at 3 T. Copyright (c)
      2015 John Wiley & Sons, Ltd.

PMID- 25762433
TI  - Now you see it, now you don't: flushing hosts prior to experimentation can
      predict their responses to brood parasitism.
AB  - Brood parasitic birds lay their eggs in other birds' nests, leaving hosts to
      raise their offspring. To understand parasite-host coevolutionary arms races,
      many studies have examined host responses to experimentally introduced eggs.
      However, attending parents often need to be flushed from their nests to add
      experimental eggs. If these birds witness parasitism events, they may recognize
      and reject foreign eggs more readily than parents who did not. We found that,
      after being flushed, female blackbirds, Turdus merula, remained close to their
      nests. Flushed females were more likely to eject foreign eggs and did so more
      quickly than females that were not flushed during experimentation. In contrast,
      flushing did not predict responses and latency to responses to parasitism by song
      thrush, Turdus philomelos, which flew farther from their nests and likely did not
      witness experimental parasitism. When statistically considering flushing,
      previously published conclusions regarding both species' response to experimental
      parasitism did not change. Nevertheless, we recommend that researchers record and
      statistically control for whether hosts were flushed prior to experimental
      parasitism. Our results have broad implications because more vigilant and/or
      bolder parents can gain more information about parasitism events and therefore
      have better chances of successfully defending against brood parasitism. 

PMID- 25762434
TI  - Clinical and genomic analysis of metastatic prostate cancer progression with a
      background of postoperative biochemical recurrence.
AB  - OBJECTIVE: To better characterize the genomics of patients with biochemical
      recurrence (BCR) who have metastatic disease progression in order to improve
      treatment decisions for prostate cancer. METHODS: The expression profiles of
      three clinical outcome groups after radical prostatectomy (RP) were compared:
      those with no evidence of disease (NED; n = 108); those with BCR (rise in
      prostate-specific antigen [PSA] level without metastasis; n = 163); and those
      with metastasis (n = 192). The patients were profiled using Human Exon 1.0 ST
      microarrays, and outcomes were supported by a median 18 years of follow-up. A
      metastasis signature was defined and verified in an independent RP cohort to
      ensure the robustness of the signature. Furthermore, bioinformatics
      characterization of the signature was conducted to decipher its biology. RESULTS:
      Minimal gene expression differences were observed between adjuvant treatment
      naive patients in the NED group and patients without metastasis in the BCR group.
      More than 95% of the differentially expressed genes (metastasis signature) were
      found in comparisons between primary tumours of metastasis patients and the two
      other outcome groups. The metastasis signature was validated in an independent
      cohort and was significantly associated with cell cycle genes, ubiquitin-mediated
      proteolysis, DNA repair, androgen, G-protein coupled and NOTCH signal
      transduction pathways. CONCLUSION: This study shows that metastasis development
      after BCR is associated with a distinct transcriptional programme that can be
      detected in the primary tumour. Patients with NED and BCR have highly similar
      transcriptional profiles, suggesting that measurement of PSA on its own is a poor
      surrogate for lethal disease. Use of genomic testing in patients undergoing RP
      with an initial rise in PSA level may be useful to improve secondary therapy
      decision-making.

PMID- 25762435
TI  - Combination therapy with ONO-KK1-300-01, a cathepsin K inhibitor, and parathyroid
      hormone results in additive beneficial effect on bone mineral density in
      ovariectomized rats.
AB  - This study examined the effects of a novel cathepsin K inhibitor, ONO-KK1-300-01
      (KK1-300), used concurrently with parathyroid hormone (PTH) in ovariectomized
      (OVX) rats. KK1-300 (3 mg/kg, twice daily), alendronate (1 mg/kg, once daily) or
      vehicle were orally administered to OVX rats for 56 days, starting the day after
      ovariectomy, followed by combination treatment with or without PTH (3 MUg/kg,
      subcutaneously three times a week) for another 28 days. OVX control animals
      exhibited a significant increase in both bone resorption (urinary
      deoxypyridinoline; DPD) and formation markers (serum osteocalcin) as well as
      microstructural changes associated with decreased bone mineral density (BMD).
      Combination treatment with KK1-300 and PTH significantly decreased urinary DPD
      and increased serum osteocalcin, indicating a sustained beneficial effect
      compared to the effect of each mono-therapy. On the other hand, combination
      therapy with alendronate and PTH weakened the PTH-induced increase in
      osteocalcin. In proximal tibia, combination treatment with KK1-300 and PTH
      increased BMD to a level significantly higher than that achieved following single
      treatment with KK1-300 or PTH alone. On the other hand, combination treatment
      with alendronate and PTH failed to produce any significant additive effect on BMD
      following single treatment with alendronate or PTH alone. Microstructural
      analysis revealed that the PTH-induced increase in bone formation (MS/BS and
      BFR/BS) was fully maintained following combination treatment with KK1-300 and
      PTH, but not following combination treatment with alendronate and PTH. These
      findings indicate that KK1-300, unlike alendronate, has an additive effect on the
      preventive action of PTH on bone loss in OVX rats.

PMID- 25762436
TI  - Histology of a Harris line in a human distal tibia.
AB  - Identification and diagnosis of Harris lines (HLs) is usually achieved using
      radiography. To date, histological methods have been mainly implemented in
      research exploring the underlying processes of HL deposition using longitudinal
      sections taken from animal bone. Here, a new insight into HL formation is
      provided following transverse histological sectioning in a human specimen. A
      distinct HL was identified macroscopically, and from a radiograph, in a left
      distal tibia taken from an adult human male. Transverse sections were taken
      through the HL, and also from trabeculae immediately superior and inferior to the
      HL. Thin sections were produced following standard histological procedures.
      Micrographs were captured using a digital microscope camera. Trabeculae
      immediately superior and inferior to the HL displayed no indication of abnormal
      growth, exhibiting abundant osteocyte lacunae and a lamellar structure. However,
      the micro-anatomy of the HL was characterised by the following three main
      features: (1) non-lamellar appearance, (2) a complete lack of osteocyte lacunae,
      and (3) presence of irregularly distributed tubular structures. These three
      histological features indicate a specific process of bone deposition, implying
      that trapping of osteoblasts may not take place during HL formation. Pictorial
      and descriptive records of HL histology are provided, aiding current
      understanding about the nature of HL, its identification from histology, and
      serving as a reference point for future comparative research. 

PMID- 25762437
TI  - Strong effect of SNP rs4988300 of the LRP5 gene on bone phenotype of Caucasian
      postmenopausal women.
AB  - The purpose of this study was to identify relationships between single nucleotide
      polymorphisms (SNPs) in the genes of the Wnt pathway and bone mineral density
      (BMD) of postmenopausal women. We chose this pathway due to its importance in
      bone metabolism that was underlined in several studies. DNA samples of 932
      Hungarian postmenopausal women were studied. First, their BMD values at different
      sites (spine, total hip) were measured, using a Lunar Prodigy DXA scanner.
      Thereafter, T-score values and the patients' body mass indices (BMIs) were
      calculated, while information about the fracture history of the sample population
      was also collected. We genotyped nine SNPs of the following three genes: LRP5,
      GPR177, and SP7, using a Sequenom MassARRAY Analyzer 4 instrument. The genomic
      DNA samples used for genotyping were extracted from the buccal mucosa of the
      subjects. Statistical analyses were carried out using the SPSS 21 and R package.
      The results of this analysis showed a significant association between SNP
      rs4988300 of the LRP5 gene and total hip BMD values. We could not reveal any
      associations between the markers of GPR177, SP7, and bone phenotypes. We found no
      effect of these genotypes on fracture risk. We could demonstrate a significant
      gene-gene interaction between two SNPs of LRP5 (rs4988300 and rs634008, p =
      0.009) which was lost after Bonferroni correction. We could firmly demonstrate a
      significant association between rs4988300 of the LRP5 gene and bone density of
      the hip on the largest homogeneous postmenopausal study group analyzed to date.
      Our finding corroborates the relationship between LRP5 genotype and bone
      phenotype in postmenopausal women, however, the complete mechanism of this
      relationship requires further investigations.

PMID- 25762438
TI  - Intracranial hypotension-like syndrome after a spinal tap test performed for
      idiopathic normal pressure hydrocephalus.
AB  - It is somewhat unexpected to have headaches in patients with idiopathic normal
      pressure hydrocephalus (INPH) for which the treatment is drainage of
      cerebrospinal fluid (CSF) using shunt. Moreover, intracranial hypotension
      syndrome (IHS) can be a challenging diagnosis, as CSF leak may be difficult to
      confirm as imaging findings can be normal. This report describes a woman with
      INPH who developed symptoms of IHS after a spinal tap test. There might be cases
      with IHS, like our case, who do not completely fulfill the current diagnostic
      criteria in terms of not having any objective evidence of intracranial
      hypotension but who also could not be explained by other conditions and recovered
      totally after classical IHS treatment. Current diagnostic criteria for IHS might
      be revised for those having normal neuroimaging and not accepting lumbar
      puncture. Nevertheless, when the history, signs, and symptoms strongly suggest
      IHS even with normal imaging, treatment should be started immediately. 

PMID- 25762439
TI  - An evolutionarily conserved DNA architecture determines target specificity of the
      TWIST family bHLH transcription factors.
AB  - Basic helix-loop-helix (bHLH) transcription factors recognize the canonical E-box
      (CANNTG) to regulate gene transcription; however, given the prevalence of E-boxes
      in a genome, it has been puzzling how individual bHLH proteins selectively
      recognize E-box sequences on their targets. TWIST is a bHLH transcription factor
      that promotes epithelial-mesenchymal transition (EMT) during development and
      tumor metastasis. High-resolution mapping of TWIST occupancy in human and
      Drosophila genomes reveals that TWIST, but not other bHLH proteins, recognizes a
      unique double E-box motif with two E-boxes spaced preferentially by 5
      nucleotides. Using molecular modeling and binding kinetic analyses, we found that
      the strict spatial configuration in the double E-box motif aligns two TWIST-E47
      dimers on the same face of DNA, thus providing a high-affinity site for a highly
      stable intramolecular tetramer. Biochemical analyses showed that the WR domain of
      TWIST dimerizes to mediate tetramer formation, which is functionally required for
      TWIST-induced EMT. These results uncover a novel mechanism for a bHLH
      transcription factor to recognize a unique spatial configuration of E-boxes to
      achieve target specificity. The WR-WR domain interaction uncovered here sets an
      example of target gene specificity of a bHLH protein being controlled
      allosterically by a domain outside of the bHLH region. 

PMID- 25762440
TI  - The RNA helicase MOV10L1 binds piRNA precursors to initiate piRNA processing.
AB  - Piwi-piRNA (Piwi-interacting RNA) ribonucleoproteins (piRNPs) enforce
      retrotransposon silencing, a function critical for preserving the genome
      integrity of germ cells. The molecular functions of most of the factors that have
      been genetically implicated in primary piRNA biogenesis are still elusive. Here
      we show that MOV10L1 exhibits 5'-to-3' directional RNA-unwinding activity in
      vitro and that a point mutation that abolishes this activity causes a failure in
      primary piRNA biogenesis in vivo. We demonstrate that MOV10L1 selectively binds
      piRNA precursor transcripts and is essential for the generation of intermediate
      piRNA processing fragments that are subsequently loaded to Piwi proteins.
      Multiple analyses suggest an intimate coupling of piRNA precursor processing with
      elements of local secondary structures such as G quadruplexes. Our results
      support a model in which MOV10L1 RNA helicase activity promotes unwinding and
      funneling of the single-stranded piRNA precursor transcripts to the endonuclease
      that catalyzes the first cleavage step of piRNA processing. 

PMID- 25762441
TI  - Autoantibodies targeting AT1 receptor from patients with acute coronary syndrome
      upregulate proinflammatory cytokines expression in endothelial cells involving NF
      kappaB pathway.
AB  - Our study intended to prove whether agonistic autoantibodies to angiotensin II
      type 1 receptor (AT1-AAs) exist in patients with coronary heart disease (CHD) and
      affect the human endothelial cell (HEC) by upregulating proinflammatory cytokines
      expression involved in NF-kappaB pathway. Antibodies were determined by
      chronotropic responses of cultured neonatal rat cardiomyocytes coupled with
      receptor-specific antagonists (valsartan and AT1-EC2) as described previously.
      Interleukin-6 (IL-6), vascular cell adhesion molecule-1 (VCAM-1), and monocyte
      chemotactic protein-1 (MCP-1) expression were improved at both mRNA and protein
      levels in HEC, while NF-kappaB in the DNA level was improved detected by
      electrophoretic mobility shift assays (EMSA). These improvements could be
      inhibited by specific AT1 receptor blocker valsartan, NF-kappaB blocker
      pyrrolidine dithiocarbamate (PDTC), and specific short peptides from the second
      extracellular loop of AT1 receptor. These results suggested that AT1-AAs, via the
      AT1 receptor, induce expression of proinflammatory cytokines involved in the
      activation of NF-kappaB. AT1-AAs may play a great role in the pathogenesis of the
      acute coronary syndrome by mediating vascular inflammatory effects involved in
      the NF-kappaB pathway. 

PMID- 25762443
TI  - New anti-angiogenic leading structure discovered in the fruit of Cimicifuga
      yunnanensis.
AB  - Cimyunnins A-C (1-3), characterized with an unusual fused cyclopentenone ring G,
      together with cimyunnin D (4), possessing a highly rearranged gamma-lactone ring
      F, were characterized from the fruit of Cimicifuga yunnanensis. Their structures
      were elucidated by spectroscopic analysis, X-ray diffraction, and density
      functional theory calculations. In addition, cimyunnin A exhibited comparable
      anti-angiogenic activities to those of sunitinib, a clinically-used first-line
      angiogenesis inhibitor, in the in vitro and ex vivo studies. 

PMID- 25762442
TI  - Associations of deceased donor kidney injury with kidney discard and function
      after transplantation.
AB  - Deceased donor kidneys with acute kidney injury (AKI) are often discarded due to
      fear of poor outcomes. We performed a multicenter study to determine associations
      of AKI (increasing admission-to-terminal serum creatinine by AKI Network stages)
      with kidney discard, delayed graft function (DGF) and 6-month estimated
      glomerular filtration rate (eGFR). In 1632 donors, kidney discard risk increased
      for AKI stages 1, 2 and 3 (compared to no AKI) with adjusted relative risks of
      1.28 (1.08-1.52), 1.82 (1.45-2.30) and 2.74 (2.0-3.75), respectively. Adjusted
      relative risk for DGF also increased by donor AKI stage: 1.27 (1.09-1.49), 1.70
      (1.37-2.12) and 2.25 (1.74-2.91), respectively. Six-month eGFR, however, was
      similar across AKI categories but was lower for recipients with DGF (48
      [interquartile range: 31-61] vs. 58 [45-75] ml/min/1.73m(2) for no DGF, p <
      0.001). There was significant favorable interaction between donor AKI and DGF
      such that 6-month eGFR was progressively better for DGF kidneys with increasing
      donor AKI (46 [29-60], 49 [32-64], 52 [36-59] and 58 [39-71] ml/min/1.73m(2) for
      no AKI, stage 1, 2 and 3, respectively; interaction p = 0.05). Donor AKI is
      associated with kidney discard and DGF, but given acceptable 6-month allograft
      function, clinicians should consider cautious expansion into this donor pool. 

PMID- 25762444
TI  - Levothyroxine requirement in congenital hypothyroidism: a 12-year longitudinal
      study.
AB  - The aim of the replacement therapy with levothyroxine in congenital
      hypothyroidism (CH) is to correct hypothyroidism and ensure normal growth and
      neuropsychological development. Few data are available about the appropriate dose
      during childhood and early adolescence; therefore, we performed a multicenter
      observational study in a large population of patients with CH to assess the
      required levothyroxine dose to obtain euthyroidism. We recruited 216 patients
      with permanent CH classified into three groups (agenesia, ectopia, and in situ
      gland) on the basis of the thyroid imaging. The levothyroxine dose was recorded
      at 6 and 12 months and then yearly until 12 years of age. The daily levothyroxine
      requirement progressively decreased during the follow-up, irrespective of
      etiology. It was significantly lower in patients with in situ gland than in
      patients with athyreosis during the entire study period and with ectopic gland
      from the age of 1 year. The levothyroxine requirement at 6 months of age was
      correlated with the requirement at each later time-point. The daily dose was
      modified less frequently in patients with in situ thyroid (36 %) than in patients
      with ectopic gland (41.4 %) or with athyreosis (43.6 %). Patients with in situ
      gland required a lower dose than the other two subgroups. The dose at 6 months
      seems predictive of the requirement until 12 years of age. Euthyroidism may be
      achieved in pre-school and in-school patients by 3-4 and 2-3 ug/kg/day (70-90 and
      60-80 ug/m(2)/day) of levothyroxine, respectively.

PMID- 25762446
TI  - A sustainable and simple catalytic system for direct alkynylation of C(sp(2))-H
      bonds with low nickel loadings.
AB  - A sustainable and simple catalytic system for the atom-economical alkynylation of
      benzamides with low nickel loadings is described. No organic or metallic oxidants
      and expensive ligands are required. A broad range of benzamides and bromoalkynes
      bearing various synthetically useful functional groups are compatible with this
      reaction. The versatility of this operationally simple protocol has been further
      demonstrated by the controllable mono- and di-alkynylation. Importantly,
      substrate/catalyst ratios of up to 200, and a turnover number of 196 were
      achieved, highlighting the potential of this protocol for synthetic applications.

PMID- 25762445
TI  - Mitochondrial SSBP1 protects cells from proteotoxic stresses by potentiating
      stress-induced HSF1 transcriptional activity.
AB  - Heat-shock response is an adaptive response to proteotoxic stresses including
      heat shock, and is regulated by heat-shock factor 1 (HSF1) in mammals.
      Proteotoxic stresses challenge all subcellular compartments including the
      mitochondria. Therefore, there must be close connections between mitochondrial
      signals and the activity of HSF1. Here, we show that heat shock triggers nuclear
      translocation of mitochondrial SSBP1, which is involved in replication of
      mitochondrial DNA, in a manner dependent on the mitochondrial permeability
      transition pore ANT-VDAC1 complex and direct interaction with HSF1. HSF1 recruits
      SSBP1 to the promoters of genes encoding cytoplasmic/nuclear and mitochondrial
      chaperones. HSF1-SSBP1 complex then enhances their induction by facilitating the
      recruitment of a chromatin-remodelling factor BRG1, and supports cell survival
      and the maintenance of mitochondrial membrane potential against proteotoxic
      stresses. These results suggest that the nuclear translocation of mitochondrial
      SSBP1 is required for the regulation of cytoplasmic/nuclear and mitochondrial
      proteostasis against proteotoxic stresses. 

PMID- 25762447
TI  - Lipidomics revealed idiopathic pulmonary fibrosis-induced hepatic lipid disorders
      corrected with treatment of baicalin in a murine model.
AB  - Idiopathic pulmonary fibrosis (IPF) is a fatal lung disease. The current standard
      treatment with glucocorticoids (GCs) leads to many adverse effects, and its
      effectiveness is questionable. Thus, it is critical and urgent to find new
      drug(s) for treatment of IPF. Baicalin (BAI) is an attractive candidate for this
      purpose. Herein, utilizing shotgun lipidomics, we revealed that IPF could lead to
      a lipid disorder of the liver in an animal model induced by bleomycin and
      confirmed through histopathological studies of the lung. Lipidomics further
      demonstrated that this disorder could virtually be corrected after treatment with
      BAI, but not with dexamethasone (DEX) (a commonly used GC for treatment of IPF).
      In contrast, the treatment with DEX did not improve IPF but led to tremendous
      alterations in hepatic lipidomes and accumulation of fat in the liver, which was
      very different from the lipid disorder induced by IPF. The underpinning
      mechanisms of the IPF-resultant lipid disorder and DEX-induced lipotoxicity as
      revealed by shotgun lipidomics were extensively discussed. Taken together, the
      current study showed that IPF could lead to hepatic lipid disorder, which can be
      treated with BAI, and demonstrated that lipidomics could be a powerful tool for
      drug screening. 

PMID- 25762449
TI  - Pharmacokinetics of Orally Inhaled Drug Products.
AB  - The presentations at the Orlando Inhalation Conference on pharmacokinetic (PK)
      studies indicated that PK is the most sensitive methodology for detecting
      formulation differences of oral inhaled drug products (OIDPs) that have
      negligible gastrointestinal bioavailability or for which oral absorption can be
      prevented (e.g., ingestion of charcoal). PK studies, therefore, may represent the
      most appropriate methodology for assessing local and systemic bioequivalence
      (BE). It was believed by many (but not all participants) that potential
      differences between formulations are more likely to be detected in healthy adult
      volunteers, as variability is reduced while deposition to peripheral areas is not
      restricted. A study design allowing assessment and statistical consideration of
      intra-subject and inter-batch variability within the evaluation of BE studies was
      suggested, while optimal inhalation technique during PK studies should be
      enforced to decrease variability. Depending on the drug and in vitro method, in
      vitro tests may not detect differences in PK parameters. Harmonization of BE
      testing requirements among different countries should be encouraged to improve
      global availability of low cost OIDPs and decrease industry burden. 

PMID- 25762448
TI  - Triple Recycling Processes Impact Systemic and Local Bioavailability of Orally
      Administered Flavonoids.
AB  - Triple recycling (i.e., enterohepatic, enteric and local recycling) plays a
      central role in governing the disposition of phenolics such as flavonoids,
      resulting in low systemic bioavailability but higher gut bioavailability and
      longer than expected apparent half-life. The present study aims to investigate
      the coexistence of these recycling schemes using model bioactive flavonoid
      tilianin and a four-site perfused rat intestinal model in the presence or absence
      of a lactase phlorizin hydrolase (LPH) inhibitor gluconolactone and/or a
      glucuronidase inhibitor saccharolactone. The result showed that tilianin could be
      metabolized into tilianin glucuronide, acacetin, and acacetin glucuronide, which
      are excreted into the bile and luminal perfusate (highest in the duodenum and
      lowest in the colon). Gluconolactone (20 mM) significantly reduced the absorption
      of tilianin and the enteric and biliary excretion of acacetin glucuronide.
      Saccharolactone (0.1 mM) alone or in combination of gluconolactone also
      remarkably reduced the biliary and intestinal excretion of acacetin glucuronide.
      Acacetin glucuronides from bile or perfusate were rapidly hydrolyzed by bacterial
      beta-glucuronidases to acacetin, enabling enterohepatic and enteric recycling.
      Moreover, saccharolactone-sensitive tilianin disposition and glucuronide
      deconjugation, which was more active in the small intestine than the colon,
      points to the small intestinal origin of the deconjugation enzyme and supports
      the presence of local recycling scheme. In conclusion, our studies have
      demonstrated triple recycling of a bioactive phenolic (i.e., a model flavonoid),
      and this recycling may have an impact on the site and duration of polyphenols
      pharmacokinetics in vivo. 

PMID- 25762450
TI  - Allosteric Binding Site and Activation Mechanism of Class C G-Protein Coupled
      Receptors: Metabotropic Glutamate Receptor Family.
AB  - Metabotropic glutamate receptors (mGluR) are mainly expressed in the central
      nervous system (CNS) and contain eight receptor subtypes, named mGluR1 to mGluR8.
      The crystal structures of mGluR1 and mGluR5 that are bound with the negative
      allosteric modulator (NAM) were reported recently. These structures provide a
      basic model for all class C of G-protein coupled receptors (GPCRs) and may aid in
      the design of new allosteric modulators for the treatment of CNS disorders.
      However, these structures are only combined with NAMs in the previous reports.
      The conformations that are bound with positive allosteric modulator (PAM) or
      agonist of mGluR1/5 remain unknown. Moreover, the structural information of the
      other six mGluRs and the comparisons of the mGluRs family have not been explored
      in terms of their binding pockets, the binding modes of different compounds, and
      important binding residues. With these crystal structures as the starting point,
      we built 3D structural models for six mGluRs by using homology modeling and
      molecular dynamics (MD) simulations. We systematically compared their allosteric
      binding sites/pockets, the important residues, and the selective residues by
      using a series of comparable dockings with both the NAM and the PAM. Our results
      show that several residues played important roles for the receptors' selectivity.
      The observations of detailed interactions between compounds and their
      correspondent receptors are congruent with the specificity and potency of
      derivatives or compounds bioassayed in vitro. We then carried out 100 ns MD
      simulations of mGluR5 (residue 26-832, formed by Venus Flytrap domain, a so
      called cysteine-rich domain, and 7 trans-membrane domains) bound with
      antagonist/NAM and with agonist/PAM. Our results show that both the NAM and the
      PAM seemed stable in class C GPCRs during the MD. However, the movements of
      "ionic lock," of trans-membrane domains, and of some activation-related residues
      in 7 trans-membrane domains of mGluR5 were congruent with the findings in class A
      GPCRs. Finally, we selected nine representative bound structures to perform 30 ns
      MD simulations for validating the stabilities of interactions, respectively. All
      these bound structures kept stable during the MD simulations, indicating that the
      binding poses in this present work are reasonable. We provided new insight into
      better understanding of the structural and functional roles of the mGluRs family
      and facilitated the future structure-based design of novel ligands of mGluRs
      family with therapeutic potential. 

PMID- 25762451
TI  - Changes in Pulmonary Function and Controlled Ventilation-High Resolution CT of
      Chest After Antibiotic Therapy in Infants and Young Children with Cystic
      Fibrosis.
AB  - BACKGROUND: Infants with cystic fibrosis (CF) develop early progressive lung
      disease which may be asymptomatic. Infant pulmonary function tests (IPFT) and
      controlled ventilation-high resolution computed tomography (CV-HRCT) of chest can
      detect early asymptomatic lung disease. It is not well established that these
      objective measures can detect changes in lung disease after clinical
      interventions. OBJECTIVE: The purpose of this study was to evaluate usefulness of
      IPFT and CV-HRCT to detect changes in lung disease after intravenous (IV)
      antibiotic therapy in infants with early CF-related lung disease. STUDY DESIGN:
      IPFTs and CV-HRCT done before and after 2 weeks of IV antibiotics in infants at
      our institution over the last 12 years were compared. CV-HRCTs were compared
      using the modified Brody scoring system. RESULTS: The sample included 21 infants,
      mean age 85.2 +/- 47.6 weeks. Mean change in weight was 0.4 +/- 0.38 kg (p =
      0.001). Significant changes in IPFT included mean % predicted FEV(0.5) (+13.5 %,
      p = 0.043), mean %FEF(25-75) (+30.2 %, p = 0.008), mean %RV/TLC (-11.2 %, p =
      0.008), and mean %FRC/TLC (-4.5 %, p = 0.001). Total Brody scores improved from a
      median of 10 to 5 (p < 0.001) as did mean scores for airway wall thickening (p =
      0.050), air trapping (p < 0.001), and parenchymal opacities (p = 0.003).
      CONCLUSION: IPFT and CV-HRCT can be used as objective measures of improvement in
      lung disease for infants with CF treated with antibiotics.

PMID- 25762452
TI  - Sclerosing hemangioma of the lung mimicking pulmonary metastasis.
AB  - Sclerosing hemangioma (SH) of the lung is a rare, benign neoplasm, initially
      thought to be of vascular origin, but immunohistochemical results suggest an
      origin from primitive respiratory epithelium. We report a case of SH initially
      misdiagnosed as malignant due to the strong FDG-PET uptake. 

PMID- 25762453
TI  - The Ratio of Free to Bound Desmosine and Isodesmosine May Reflect Emphysematous
      Changes in COPD.
AB  - BACKGROUND: The unique elastin crosslinks, desmosine and isodesmosine (DID) are
      significantly elevated in blood, urine, and sputum from patients with COPD, and
      may decline following treatment of the disease. However, the large degree of
      variance in this biomarker among COPD patients with similar levels of disease
      suggests that it has limited prognostic value with regard to the degree of lung
      disease in a given individual. As an alternative to measuring the total amount of
      DID, we propose using the ratio of free to peptide-bound DID, which may provide a
      better indication of overall lung disease. METHODS: To test this hypothesis, the
      free/bound DID ratio was measured in bronchoalveolar lavage fluid (BALF) from
      both hamsters with elastase-induced emphysema and controls not given the enzyme,
      using a combination of liquid chromatography and tandem mass spectroscopy. This
      ratio was then correlated with airspace enlargement, as measured by the mean
      percentage of lung surface area at *100 microscopic magnification. RESULTS: There
      was a significant negative correlation between the free/bound DID ratio in BALF
      and lung surface area. However, there was no correlation between this ratio and
      total BALF DID, suggesting that free/bound DID is unrelated to the immediate rate
      of breakdown of elastic fibers, and may instead measure the cumulative effect of
      elastase injury in the lung. CONCLUSIONS: The free/bound DID ratio may be a
      useful measure of emphysematous changes in the lung and might also serve as a
      screening procedure for healthy smokers and other individuals at risk for
      developing COPD.

PMID- 25762454
TI  - Evaluating the Precision of Preoperative Planning in Patient Specific
      Instrumentation: Can a Single MRI Yield Different Preoperative Plans?
AB  - If PSI preoperative planning were perfectly precise, a single MRI would give rise
      to one preoperative plan. Our purpose was to determine whether a single MRI
      inputted into two different PSI software yielded differences in preoperative
      alignment determination, component sizing, and bone resection within the
      preoperative plan. This prospective comparative study evaluated 40 preoperative
      plans generated by two PSI software given identical MRI. Femoral and tibial
      component sizes differed between software in 37.5% and 30.0% of cases,
      respectively. The maximum difference in bone resection between software ranged
      from 2.2mm to 5.1mm. Surgeons should be prepared to intraoperatively deviate from
      PSI selected size by 1 size. It may be necessary to fine tune soft tissue
      balancing when using a PSI system. 

PMID- 25762455
TI  - amamutdb.no: A relational database for MAN2B1 allelic variants that compiles
      genotypes, clinical phenotypes, and biochemical and structural data of mutant
      MAN2B1 in alpha-mannosidosis.
AB  - alpha-Mannosidosis is an autosomal recessive lysosomal storage disorder caused by
      mutations in the MAN2B1 gene, encoding lysosomal alpha-mannosidase. The disorder
      is characterized by a range of clinical phenotypes of which the major
      manifestations are mental impairment, hearing impairment, skeletal changes, and
      immunodeficiency. Here, we report an alpha-mannosidosis mutation database,
      amamutdb.no, which has been constructed as a publicly accessible online resource
      for recording and analyzing MAN2B1 variants (http://amamutdb.no). Our aim has
      been to offer structured and relational information on MAN2B1 mutations and
      genotypes along with associated clinical phenotypes. Classifying missense
      mutations, as pathogenic or benign, is a challenge. Therefore, they have been
      given special attention as we have compiled all available data that relate to
      their biochemical, functional, and structural properties. The alpha-mannosidosis
      mutation database is comprehensive and relational in the sense that information
      can be retrieved and compiled across datasets; hence, it will facilitate
      diagnostics and increase our understanding of the clinical and molecular aspects
      of alpha-mannosidosis. We believe that the amamutdb.no structure and architecture
      will be applicable for the development of databases for any monogenic disorder.

PMID- 25762457
TI  - NHS England announces 29 sites to spearhead integrated care models.

PMID- 25762456
TI  - Methods for transition toward computer assisted cognitive examination.
AB  - INTRODUCTION: We present a software framework which enables the extension of
      current methods for the assessment of cognitive fitness using recent
      technological advances. BACKGROUND: Screening for cognitive impairment is
      becoming more important as the world's population grows older. Current methods
      could be enhanced by use of computers. Introduction of new methods to clinics
      requires basic tools for collection and communication of collected data.
      OBJECTIVES: To develop tools that, with minimal interference, offer new
      opportunities for the enhancement of the current interview based cognitive
      examinations. METHODS: We suggest methods and discuss process by which
      established cognitive tests can be adapted for data collection through
      digitization by pen enabled tablets. We discuss a number of methods for
      evaluation of collected data, which promise to increase the resolution and
      objectivity of the common scoring strategy based on visual inspection. By
      involving computers in the roles of both instructing and scoring, we aim to
      increase the precision and reproducibility of cognitive examination. RESULTS: The
      tools provided in Python framework CogExTools available at http://bsp.
      brain.riken.jp/cogextools/ enable the design, application and evaluation of
      screening tests for assessment of cognitive impairment. The toolbox is a research
      platform; it represents a foundation for further collaborative development by the
      wider research community and enthusiasts. It is free to download and use, and
      open-source. CONCLUSION: We introduce a set of open-source tools that facilitate
      the design and development of new cognitive tests for modern technology. We
      provide these tools in order to enable the adaptation of technology for cognitive
      examination in clinical settings. The tools provide the first step in a possible
      transition toward standardized mental state examination using computers.

PMID- 25762458
TI  - An electronic medical record system with treatment recommendations based on
      patient similarity.
AB  - As the core of health information technology (HIT), electronic medical record
      (EMR) systems have been changing to meet health care demands. To construct a new
      generation EMR system framework with the capability of self-learning and real
      time feedback, thus adding intelligence to the EMR system itself, this paper
      proposed a novel EMR system framework by constructing a direct pathway between
      the EMR workflow and EMR data. A prototype of this framework was implemented
      based on patient similarity learning. Patient diagnoses, demographic data, vital
      signs and structured lab test results were considered for similarity
      calculations. Real hospitalization data from 12,818 patients were substituted,
      and Precision @ Position measurements were used to validate self-learning
      performance. Our EMR system changed the way in which orders are placed by
      establishing recommendation order menu and shortcut applications. Two learning
      modes (EASY MODE and COMPLEX MODE) were provided, and the precision values @
      position 5 of both modes were 0.7458 and 0.8792, respectively. The precision
      performance of COMPLEX MODE was better than that of EASY MODE (tested using a
      paired Wilcoxon-Mann-Whitney test, p < 0.001). Applying the proposed framework,
      the EMR data value was directly demonstrated in the clinical workflow, and
      intelligence was added to the EMR system, which could improve system usability,
      reliability and the physician's work efficiency. This self-learning mechanism is
      based on dynamic learning models and is not limited to a specific disease or
      clinical scenario, thus decreasing maintenance costs in real world applications
      and increasing its adaptability.

PMID- 25762459
TI  - Where we are with point-of-care testing.
AB  - Viral hepatitis claims one million lives each year. Scaling up treatment for
      hepatitis B and C in resource-limited settings is not possible without access to
      reliable diagnostic tools. This article gives an overview of current technologies
      and the pipeline for easy-to-use assays for serological and virological analyses,
      which can be performed at the site of patient care ('point-of-care assays').
      Furthermore, the utility of dried blood spots for hepatitis B and C viral load
      testing is discussed. In addition to simple and reliable diagnostics, there is a
      need for a sustainable funding scheme and generic production of antiviral drugs
      to reduce the burden of viral hepatitis worldwide. 

PMID- 25762460
TI  - Rainwater in cupulate bracts repels seed herbivores in a bumblebee-pollinated
      subalpine flower.
AB  - Floral herbivory may have deleterious effects on the reproductive success of
      flowering plants. However, plants may evolve floral traits that allow them to
      defend against herbivory in particular conditions. A bumblebee-pollinated
      subalpine herb, Pedicularis rex (Orobanchaceae), endemic to southwest China, has
      cup-like bracts that fill with rainwater, which submerges its corolla tubes. We
      hypothesized that these water-filled cupulate bracts function to deter nectar
      robbers and/or seed herbivores. To test these hypotheses, we experimentally
      drained bracts and measured both the response of mutualistic floral visitors and
      antagonistic nectar robbers and seed predators and their effects on seed
      production. Our observations revealed that neither nectar robbers nor legitimate
      pollinators discriminated between water-drained flowers and intact controls.
      However, seed predation significantly increased in drained flowers, suggesting
      that water-filled bracts help protect the flowers from seed herbivores. The water
      filled bracts in P. rex may represent an adaptation to reduce floral herbivory in
      a high-rainfall environment. 

PMID- 25762461
TI  - Two cilengitide regimens in combination with standard treatment for patients with
      newly diagnosed glioblastoma and unmethylated MGMT gene promoter: results of the
      open-label, controlled, randomized phase II CORE study.
AB  - BACKGROUND: Survival outcomes for patients with glioblastoma remain poor,
      particularly for patients with unmethylated O(6)-methylguanine-DNA
      methyltransferase (MGMT) gene promoter. This phase II, randomized, open-label,
      multicenter trial investigated the efficacy and safety of 2 dose regimens of the
      selective integrin inhibitor cilengitide combined with standard chemoradiotherapy
      in patients with newly diagnosed glioblastoma and an unmethylated MGMT promoter.
      METHODS: Overall, 265 patients were randomized (1:1:1) to standard cilengitide
      (2000 mg 2*/wk; n = 88), intensive cilengitide (2000 mg 5*/wk during wk 1-6,
      thereafter 2*/wk; n = 88), or a control arm (chemoradiotherapy alone; n = 89).
      Cilengitide was administered intravenously in combination with daily temozolomide
      (TMZ) and concomitant radiotherapy (RT; wk 1-6), followed by TMZ maintenance
      therapy (TMZ/RT->TMZ). The primary endpoint was overall survival; secondary
      endpoints included progression-free survival, pharmacokinetics, and safety and
      tolerability. RESULTS: Median overall survival was 16.3 months in the standard
      cilengitide arm (hazard ratio [HR], 0.686; 95% CI: 0.484, 0.972; P = .032) and
      14.5 months in the intensive cilengitide arm (HR, 0.858; 95% CI: 0.612, 1.204; P
      = .3771) versus 13.4 months in the control arm. Median progression-free survival
      assessed per independent review committee was 5.6 months (HR, 0.822; 95% CI:
      0.595, 1.134) and 5.9 months (HR, 0.794; 95% CI: 0.575, 1.096) in the standard
      and intensive cilengitide arms, respectively, versus 4.1 months in the control
      arm. Cilengitide was well tolerated. CONCLUSIONS: Standard and intensive
      cilengitide dose regimens were well tolerated in combination with TMZ/RT->TMZ.
      Inconsistent overall survival and progression-free survival outcomes and a
      limited sample size did not allow firm conclusions regarding clinical efficacy in
      this exploratory phase II study.

PMID- 25762462
TI  - Reproducibility of phase rotation stimulated echo acquisition mode at 3T in
      schizophrenia: Emphasis on glutamine.
AB  - PURPOSE: To determine the reproducibility and reliability of glutamine (Gln),
      measured with a very short echo time phase rotation stimulated echo acquisition
      mode (VTE-PR STEAM) sequence at 3T, in subjects with schizophrenia. METHODS:
      Seven subjects with schizophrenia were scanned twice with VTE-PR STEAM in a
      Siemens 3T TIM Trio scanner with a 32-channel head coil. Spectroscopic data were
      collected from two voxels in gray matter, one in the dorsal anterior cingulate
      and the other in the medial occipital cortex. Reproducibility was assessed using
      coefficients of variation (CVs) and reliability with standard error of
      measurement and intraclass correlations (ICCs). Phantoms containing increasing
      concentrations of Gln in a physiologic solution of other neurometabolites with
      overlapping resonances were scanned to assess the validity of spectral Gln
      measurement. RESULTS: Very good reliability and reproducibility for Gln in both
      regions of interest were supported by CVs of <=10.0% and ICCs of >=0.6,
      respectively. Phantom studies documented a robust correspondence between known
      Gln concentrations and VTE-PR STEAM measurements of this metabolite (R(2)  =
      0.988). CONCLUSION: The VTE-PR STEAM approach at 3T permits the longitudinal
      assessment of Gln and other (1) H MR spectroscopy neurometabolites in a
      clinically plausible setting.

PMID- 25762463
TI  - Between-day reliability of the trapezius muscle H-reflex and M-wave.
AB  - INTRODUCTION: The aim of this study was to investigate the between-day
      reliability of the trapezius muscle H-reflex and M-wave. METHODS: Sixteen healthy
      subjects were studied on 2 consecutive days. Trapezius muscle H-reflexes were
      evoked by electrical stimulation of the C3/4 cervical nerves; M-waves were evoked
      by electrical stimulation of the accessory nerve. Relative reliability was
      estimated by intraclass correlation coefficients (ICC2,1 ). Absolute reliability
      was estimated by computing the standard error of measurement (SEM) and the
      smallest real difference (SRD). Bland-Altman plots were constructed to detect any
      systematic bias. RESULTS: Variables showed substantial to excellent relative
      reliability (ICC = 0.70-0.99). The relative SEM ranged from 1.4% to 34.8%;
      relative SRD ranged from 3.8% to 96.5%. No systematic bias was present in the
      data. CONCLUSIONS: The amplitude and latency of the trapezius muscle H-reflex and
      M-wave in healthy young subjects can be measured reliably across days.

PMID- 25762464
TI  - Reply: Does imitation act as an oxytocin nebulizer in autism spectrum disorder?

PMID- 25762466
TI  - Study skills in anatomy and physiology: Is there a difference?
AB  - Many factors influence the way individual students study, including but not
      limited to: previous coursework, attitudes toward the class (motivation,
      intimidation, risk, etc.), metacognition, and work schedules. However, little of
      this research has involved medical students. The present article asks the
      question, "Do individual medical students study differently for different
      classes?" Study skills surveys were given to United States medical students at an
      allopathic medical school and an osteopathic medical school. Students were
      surveyed near the end of their first year gross anatomy course and again near the
      end of their first year physiology course. Survey items included Likert scale and
      open-ended questions about study habits and basic demographic information. The
      survey responses were correlated with each student's final grade percentages in
      the courses. Analysis revealed that the four most common study habits were
      reviewing lecture notes, taking practice examinations, completing learning
      exercises, and making drawings and diagrams. The two surveys (anatomy and
      physiology) from each individual were also compared to see if students reported
      different study habits in anatomy versus physiology. A negative correlation was
      found between changing study habits between courses and final anatomy grade
      percentages. Additional analyses suggest that those students who do change their
      study habits between courses are increasing the number of study strategies that
      they attempt. This increase in the number of study strategies attempted may not
      allow the student to reach the same depth of understanding as their colleagues
      who utilize fewer strategies.

PMID- 25762465
TI  - Memory binding and white matter integrity in familial Alzheimer's disease.
AB  - Binding information in short-term and long-term memory are functions sensitive to
      Alzheimer's disease. They have been found to be affected in patients who meet
      criteria for familial Alzheimer's disease due to the mutation E280A of the PSEN1
      gene. However, only short-term memory binding has been found to be affected in
      asymptomatic carriers of this mutation. The neural correlates of this
      dissociation are poorly understood. The present study used diffusion tensor
      magnetic resonance imaging to investigate whether the integrity of white matter
      structures could offer an account. A sample of 19 patients with familial
      Alzheimer's disease, 18 asymptomatic carriers and 21 non-carrier controls
      underwent diffusion tensor magnetic resonance imaging, neuropsychological and
      memory binding assessment. The short-term memory binding task required
      participants to detect changes across two consecutive screens displaying arrays
      of shapes, colours, or shape-colour bindings. The long-term memory binding task
      was a Paired Associates Learning Test. Performance on these tasks were entered
      into regression models. Relative to controls, patients with familial Alzheimer's
      disease performed poorly on both memory binding tasks. Asymptomatic carriers
      differed from controls only in the short-term memory binding task. White matter
      integrity explained poor memory binding performance only in patients with
      familial Alzheimer's disease. White matter water diffusion metrics from the
      frontal lobe accounted for poor performance on both memory binding tasks.
      Dissociations were found in the genu of corpus callosum which accounted for short
      term memory binding impairments and in the hippocampal part of cingulum bundle
      which accounted for long-term memory binding deficits. The results indicate that
      white matter structures in the frontal and temporal lobes are vulnerable to the
      early stages of familial Alzheimer's disease and their damage is associated with
      impairments in two memory binding functions known to be markers for Alzheimer's
      disease. 

PMID- 25762467
TI  - TALEN mediated targeted editing of GM2/GD2-synthase gene modulates anchorage
      independent growth by reducing anoikis resistance in mouse tumor cells.
AB  - Complex ganglioside expression is highly deregulated in several tumors which is
      further dependent on specific ganglioside synthase genes. Here, we designed and
      constructed a pair of highly specific transcription-activator like effector
      endonuclease (TALENs) to disrupt a particular genomic locus of mouse GM2
      synthase, a region conserved in coding sequence of all four transcript variants
      of mouse GM2-synthase. Our designed TALENs effectively work in different mouse
      cell lines and TALEN induced mutation rate is over 45%. Clonal selection strategy
      is undertaken to generate stable GM2-synthase knockout cell line. We have also
      demonstrated non-homologous end joining (NHEJ) mediated integration of neomycin
      cassette into the TALEN targeted GM2-synthase locus. Functionally, clonally
      selected GM2-synthase knockout clones show reduced anchorage-independent growth
      (AIG), reduction in tumor growth and higher cellular adhesion as compared to wild
      type Renca-v cells. Insight into the mechanism shows that, reduced AIG is due to
      loss in anoikis resistance, as both knockout clones show increased sensitivity to
      detachment induced apoptosis. Therefore, TALEN mediated precise genome editing at
      GM2-synthase locus not only helps us in understanding the function of GM2
      synthase gene and complex gangliosides in tumorigenicity but also holds
      tremendous potential to use TALENs in translational cancer research and
      therapeutics. 

PMID- 25762468
TI  - Three-dimensional rotational angiography in the assessment of vascular and airway
      compression in children after a cavopulmonary anastomosis.
AB  - The aim of the study was to examine the role of three-dimensional rotational
      angiography (3DRA) in assessing vascular and airway narrowing in children with a
      bidirectional cavopulmonary anastomosis (BCPA). The course of children with
      single ventricle physiology is often complicated by left pulmonary artery (LPA)
      and/or bronchial stenosis and may be related to aortic compression. 3DRA may be
      useful in evaluating this complex anatomy and possible mechanisms for the
      observed obstruction. Clinical data and imaging (2D angiography and 3DRA) of
      children with a BCPA were reviewed retrospectively. Measurements were taken at
      similar locations along the pulmonary arteries in both modalities and in the
      airways on 3DRA. Twenty-five children with a previous BCPA were assessed at mean
      age of 3.1 +/- 2.0 years and weight of 13.6 +/- 3.6 kg. Excellent correlation was
      found between 3DRA and 2D angiographic LPA measurements (r = 0.89, p < 0.0001).
      Twelve children had qualitative LPA stenosis on 3DRA, with a stenotic dimension
      of 6.6 +/- 2.2 mm on 2D angiography and 6.8 +/- 1.9 mm on 3DRA (r = 0.94, p <
      0.0001). Ten cases with LPA stenosis also had bronchial stenosis (83 %).
      Qualitative airway assessment correlated with quantitative bronchial dimensions
      from 3DRA-derived tomographic images: Bronchial stenosis measured 4.4 +/- 1.6
      versus 5.9 +/- 1.1 mm in those with a normal appearing bronchus (p = 0.009).
      Hybrid patients (initial palliation with bilateral pulmonary artery banding and
      arterial ductal stenting, n = 5) and all patients with a Damus-Kaye-Stansel (DKS)
      anastomosis (n = 9) were more likely to have LPA and left bronchial stenosis (OR
      7.7, p = 0.04). 3DRA is a useful and accurate tool in assessment of LPA and
      airway narrowing after BCPA. Hybrid and DKS patients are more prone to LPA and
      bronchial stenosis, and 3DRA can provide insight into the mechanism.

PMID- 25762469
TI  - Tetralogy of Fallot with left superior vena cava and coronary sinus atrial septal
      defect: a rare association.
AB  - This report describes a rare case of Tetralogy of Fallot with associated left
      superior vena cava and coronary sinus atrial septal defect. The initial diagnosis
      was made by echocardiography. The patient underwent complete repair at 2 months
      of age. Her postoperative course was complicated by low cardiac output requiring
      ECMO. She was subsequently weaned off of ECMO and discharged home. She continues
      to do well on serial follow-up.

PMID- 25762470
TI  - Magnesium Lowers the Incidence of Postoperative Junctional Ectopic Tachycardia in
      Congenital Heart Surgical Patients: Is There a Relationship to Surgical Procedure
      Complexity?
AB  - Magnesium sulfate was given to pediatric cardiac surgical patients during
      cardiopulmonary bypass period in an attempt to reduce the occurrence of
      postoperative junctional ectopic tachycardia (PO JET). We reviewed our data to
      evaluate the effect of magnesium on the occurrence of JET and assess a possible
      relationship between PO JET and procedure complexity. A total of 1088 congenital
      heart surgeries (CHS), performed from 2005 to 2010, were reviewed. A total of 750
      cases did not receive magnesium, and 338 cases received magnesium (25 mg/kg). All
      procedures were classified according to Aristotle score from 1 to 4. Overall,
      there was a statistically significant decrease in PO JET occurrence between the
      two groups regardless of the Aristotle score, 15.3 % (115/750) in non-magnesium
      group versus 7.1 % (24/338) in magnesium group, P < 0.001. In the absence of
      magnesium, the risk of JET increased with increasing Aristotle score, P = 0.01.
      Following magnesium administration and controlling for body weight, surgical and
      aortic cross-clamp times in the analyses, reduction in adjusted risk of JET was
      significantly greater with increasing Aristotle level of complexity (JET in non
      magnesium vs. magnesium group, Aristotle level 1: 9.8 vs. 14.3 %, level 4: 11.5
      vs. 3.2 %; odds ratio 0.54, 95 % CI 0.31-0.94, P = 0.028). Our data confirmed
      that intra-operative usage of magnesium reduced the occurrence of PO JET in a
      larger number and more diverse group of CHS patients than has previously been
      reported. Further, our data suggest that magnesium's effect on PO JET occurrence
      seemed more effective in CHS with higher levels of Aristotle complexity.

PMID- 25762471
TI  - Incomplete Kawasaki disease with coronary artery aneurysm and coronary sinus
      thrombus.
AB  - We describe herein a rare case of coronary artery aneurysm and coronary sinus
      thrombus due to incomplete Kawasaki disease. To the best of our knowledge,
      coronary sinus thrombosis has not previously been reported as a complication of
      this disease. Our patient underwent thrombolytic therapy with a good response. 

PMID- 25762472
TI  - Anthocyanins and Phenolic Acids of Hybrid and Native Blue Maize (Zea mays L.)
      Extracts and Their Antiproliferative Activity in Mammary (MCF7), Liver (HepG2),
      Colon (Caco2 and HT29) and Prostate (PC3) Cancer Cells.
AB  - Blue maize is an excellent source of bioactive components such as phenolic acids
      and anthocyanins but when it is processed for human consumption, these compounds
      decrease considerably. Therefore, blue maize could be directed to produce
      nutraceutical extracts. The aim of this study was to evaluate the relation
      between anthocyanins composition of acidified and non-acidified extracts from
      native and hybrid blue maize genotypes and their antiproliferative effect in
      mammary (MCF7), liver (HepG2), colon (Caco2 and HT29) and prostate (PC3) cancer
      cells. The most abundant phenolic acid was ferulic acid. Nine anthocyanins were
      quantified in the extracts, being Cy3-Glu the most abundant. Acylated forms were
      also obtained in high abundance depending of the extraction method. An extract
      concentration range of 4.31 to 7.23 mg/mL inhibited by 50% the growth of
      untransformed cells NIH3T3. Antiproliferative effect on PC3, Caco2, HepG2 and
      MCF7 cancer cells of acidified extracts from hybrid blue maize was larger than
      the observed using non-acidified extracts. Among the nine compounds that were
      quantified in the extracts tested, CyMalGlu I showed the strongest correlation
      with the reduction of cell viability in Caco2 (-0.876), HepG2 (-0.813), MCF7 (
      0.765) and PC3 (-0.894). No significant correlation or differences in
      antiproliferative effect on HT29 was found among the extracts. The method of
      extraction of maize anthocyanins must be selected to obtain a high yield of
      CyMalGlu I more than only Cy3-Glu since acylation affects the inhibition of
      cancer cell growth.

PMID- 25762473
TI  - Implementing quality measures for inflammatory bowel disease.
AB  - Variation in care for inflammatory bowel disease (IBD) is present across multiple
      aspects of IBD management, suggesting overall poor quality of care. Quality
      indicators are intended to provide clear, measurable processes and outcomes of
      quality care. Initial sets of process and outcome measures have been developed to
      address areas of inconsistent care and to allow for standardized measurement of
      outcomes. Measures developed by the Crohn's and Colitis Foundation of America
      (CCFA) are intended to provide measurable standards for improvement in care.
      These measure sets will warrant updates overtime to best represent gaps in IBD
      management. Practically, implementation of quality measures may depend on the
      care setting and whether quality measurement and improvement can be incorporated
      into workflows and electronic medical records. Collaborative networks,
      utilization of care pathways, and standardized treatment algorithms may represent
      avenues for wide-scale implementation of quality improvement. Implementation
      efforts should assess the impact on outcomes in order to identify successful
      models for improvement in IBD care. 

PMID- 25762476
TI  - The association between glucose-lowering drug use and mortality among breast
      cancer patients with type 2 diabetes.
AB  - This study assessed the association between glucose-lowering drug (GLD) use,
      including metformin, sulphonylurea derivatives and insulin, after breast cancer
      diagnosis and breast cancer-specific and all-cause mortality. 1763 breast cancer
      patients, diagnosed between 1998 and 2010, with type 2 diabetes were included.
      Cancer information was retrieved from English cancer registries, prescription
      data from the UK Clinical Practice Research Datalink and mortality data from the
      Office of National Statistics (up to January 2012). Time-varying Cox regression
      models were used to calculate HRs and 95 % CIs for the association between GLD
      use and breast cancer-specific and all-cause mortality. In 1057 patients with
      diabetes before breast cancer, there was some evidence that breast cancer
      specific mortality decreased with each year of metformin use (adjusted HR 0.88;
      95 % CI 0.75-1.04), with a strong association seen with over 2 years of use
      (adjusted HR 0.47; 95 % CI 0.26-0.82). Sulphonylurea derivative use for less than
      2 years was associated with increased breast cancer-specific mortality (adjusted
      HR 1.70; 95 % CI 1.18-2.46), but longer use was not (adjusted HR 0.94; 95 % CI
      0.54-1.66). In 706 patients who developed diabetes after breast cancer, similar
      patterns were seen for metformin, but sulphonylurea derivative use was strongly
      associated with cancer-specific mortality (adjusted HR 3.64; 95 % CI 2.16-6.16),
      with similar estimates for short- and long-term users. This study provides some
      support for an inverse association between, mainly long-term, metformin use and
      (breast cancer-specific) mortality. In addition, sulphonylurea derivative use was
      associated with increased breast cancer-specific mortality, but this should be
      interpreted cautiously, as it could reflect selective prescribing in advanced
      cancer patients.

PMID- 25762474
TI  - IBD and the gut microbiota--from bench to personalized medicine.
AB  - Inflammatory bowel diseases (IBD) are chronic relapsing inflammatory disorders
      involving the gastrointestinal (GI) tract, which arise from the confluence of
      genetic, immunological, microbial, and environmental factors. Clinical, genetic,
      and experimental data support the role of gut microbiota in contributing to the
      etiopathogenesis of these diseases. In IBD, the development of gut dysbiosis and
      imbalances in host-microbe relationships contribute to the extent, severity, and
      chronicity of intestinal inflammation. With continued advances in knowledge,
      technology, bioinformatics tools, and capabilities to define disease subsets, we
      will be able to lower risk and improve clinical outcomes in IBD through
      individualized interventions that restore host-microbial balance. This article
      provides a critical review of the field, based on the latest clinical and
      experimental information. 

PMID- 25762475
TI  - Revisiting the estrogen receptor pathway and its role in endocrine therapy for
      postmenopausal women with estrogen receptor-positive metastatic breast cancer.
AB  - Endocrine therapy (ET) is the most commonly administered first-line systemic
      therapy for estrogen receptor-positive (ER+) metastatic breast cancer (MBC).
      Manipulation of hormone levels was one of the earliest ET approaches. However,
      treatment modalities have since evolved with the growing understanding of
      estrogen biosynthesis and ER biology. The current armamentarium of ET includes
      selective estrogen receptor modulation, aromatase inhibition, and selective
      estrogen receptor downregulation. However, intrinsic or acquired resistance to ET
      is frequently observed. Significant strides have been made in recent years in our
      understanding of the mechanisms of resistance to ET, and several targeted
      approaches including inhibitors against the phosphatidylinositol 3
      kinase/mammalian target of rapamycin (PI3K/mTOR) pathway and cyclin-dependent
      kinase 4/6 (CDK4/6) have shown great promise. The mTOR inhibitor, everolimus, is
      already in clinical use for the treatment of resistant ER+MBC. However, multiple
      levels of evidence indicate that ER signaling remains as an important therapeutic
      target even in the resistance setting, providing the rationale for sequencing
      multiple lines and combinations of ET. In addition, recurrent mutations in
      estrogen receptor 1 (ESR1), the gene that encodes the ER, have been identified in
      the genomic studies of metastatic ER+ breast cancer. ESR1 mutations are an
      important mechanism for acquired resistance, and effective ER targeting in this
      setting is particularly important. 

PMID- 25762477
TI  - BI-RADS update for breast cancer caregivers.
AB  - This review will discuss changes relevant to breast cancer caregivers in the
      fifth edition of the Breast Imaging Reporting and Data System. 

PMID- 25762478
TI  - Quantitative assessment of HER2 amplification in HER2-positive breast cancer: its
      association with clinical outcomes.
AB  - Human epidermal growth factor receptor 2 (HER2) is an effective therapeutic
      target in breast cancer. However, not all patients benefit from trastuzumab-based
      therapy. We aimed to investigate whether patients with different levels of HER2
      amplification would experience different clinical outcomes with trastuzumab-based
      chemotherapy. We quantified the HER2 gene copy number (GCN) and HER2/centromere
      chromosome probe 17 (CEP17) ratio in 291 breast cancer patients with HER2
      amplification confirmed by immunohistochemistry and fluorescence in situ
      hybridization. The optimal cutoff points for HER2 GCN and the HER2/CEP17 ratios
      for distinguishing positive results were determined by receiver operating
      characteristic (ROC) curve analyses. ROC analysis identified optimal cutoff
      points for HER2 GCN and HER2/CEP17 ratios as 11.5 and 6.5 (P = 0.039 and P =
      0.012), respectively. The DFS in patients with HER2 GCN <11.5 was significantly
      longer than in HER2 GCN >=11.5 patients (P = 0.015) according to Kaplan-Meier
      survival curves analysis. Similarly, patients with HER2/CEP17 ratios <6.5 had a
      significantly longer DFS than those with HER2/CEP17 ratios >=6.5 (P = 0.013).
      Moreover, patients with HER2 cluster amplification showed a worse survival than
      those with HER2 non-cluster amplification (P = 0.041). This study demonstrated a
      significant association between the level of HER2 amplification and survival time
      in a relatively large cohort of HER2-positive breast cancer patients undergoing
      trastuzumab-based chemotherapy. Further investigations of more precise
      quantitative measurements and larger cohorts are required to define this
      threshold.

PMID- 25762479
TI  - Clinical and biological significance of glucocorticoid receptor (GR) expression
      in breast cancer.
AB  - The glucocorticoid receptor (GR) is a member of the nuclear receptor superfamily
      of transcription factors, which exerts anti-proliferative and anti-apoptotic
      activities. The GR is expressed in a large proportion of breast cancer (BC)
      although levels generally decrease during cancer progression. This study aimed to
      determine the clinical and biological significance of GR expression using a large
      series of early-stage BC with long-term follow-up and BC cell lines.
      Immunohistochemistry was used to assess the expression of GR in 999 cases of
      primary invasive BC prepared as tissue microarrays. Reverse phase protein
      microarray was used to assess the expression of GR in MCF7 and MDA-MB-231 cell
      lines. Nuclear expression of GR was observed in 61.6 % of breast tumours and was
      associated with features of good prognosis including smaller tumour size and
      lower grade with less pleomorphism and low mitotic count. GR expression was
      positively correlated with expression of oestrogen (ER) and progesterone
      receptors. In ER-positive tumours, GR was associated with other features of
      favourable outcome including FOXA1, GATA3 and BEX1 expression, while low GR
      expression was associated with high Ki67, p53 and CD71 expression. GR expression
      is associated with features of good outcome but does not provide prognostic
      information independent of size, stage and grade. Understanding the receptor and
      its effects on BC behaviour is essential for avoiding any unwanted effects from
      the use of glucocorticoids in routine oncology practice.

PMID- 25762480
TI  - Perceptions of Contralateral Breast Cancer Risk: A Prospective, Longitudinal
      Study.
AB  - PURPOSE: An increasing proportion of breast cancer patients undergo contralateral
      prophylactic mastectomy (CPM) to reduce their risk of contralateral breast cancer
      (CBC). Our goal was to evaluate CBC risk perception changes over time among
      breast cancer patients. METHODS: We conducted a prospective, longitudinal study
      of women with newly diagnosed unilateral breast cancer. Patients completed a
      survey before and approximately 2 years after treatment. Survey questions used
      open-ended responses or 5-point Likert scale scoring (e.g., 5 = very likely, 1 =
      not at all likely). RESULTS: A total of 74 women completed the presurgical
      treatment survey, and 43 completed the postsurgical treatment survey. Baseline
      characteristics were not significantly different between responders and
      nonresponders of the follow-up survey. The mean estimated 10-year risk of CBC was
      35.7 % on the presurgical treatment survey and 13.8 % on the postsurgical
      treatment survey (p < 0.001). The perceived risks of developing cancer in the
      same breast and elsewhere in the body significantly decreased between surveys.
      Both CPM and non-CPM (breast-conserving surgery or unilateral mastectomy)
      patients' perceived risk of CBC significantly decreased from pre- to postsurgical
      treatment surveys. Compared with non-CPM patients, CPM patients had a
      significantly lower perceived 10-year risk of CBC (5.8 vs. 17.3 %, p = 0.046) on
      postsurgical treatment surveys. CONCLUSIONS: The perceived risk of CBC
      significantly attenuated over time for both CPM and non-CPM patients. These data
      emphasize the importance of early physician counseling and improvement in patient
      education to provide women with accurate risk information before they make
      surgical treatment decisions.

PMID- 25762481
TI  - The Impact of Surgical Margin Status on Long-Term Outcome After Resection for
      Intrahepatic Cholangiocarcinoma.
AB  - BACKGROUND: The influence of margin status on long-term outcome of patients
      undergoing liver resection for intrahepatic cholangiocarcinoma (ICC) remains
      controversial. We sought to study the impact of surgical tumor margin status on
      recurrence-free survival (RFS) and overall survival (OS) of patients undergoing
      resection for ICC. METHODS: From a multi-institutional database, 583 patients who
      underwent hepatic resection for ICC were identified. Demographics data, operative
      details, pathologic margin status, and long-term outcomes were collected and
      analyzed. RESULTS: Margin status was positive (R1) in 95 (17.8 %) patients; among
      patients who underwent an R0 resection (80.9 %), margin width was negative by 1-4
      mm in 166 (31.0 %) patients, 5-9 mm in 100 (18.7 %) patients, and >=1 cm in 174
      (32.5 %) patients. Overall, 379 (65.0 %) patients had a recurrence: 61.5 %
      intrahepatic, 13.5 % extrahepatic, and 25.0 % both intra- and extrahepatic.
      Median and 5-year RFS and OS was 10.0 months and 9.2 %, and 26.4 months and 23.0
      %, respectively. Patients who had an R1 resection had a higher risk of recurrence
      (hazard ratio [HR] 1.61, 95 % CI 1.15-2.27; p = 0.01) and shorter OS (HR 1.54, 95
      % CI 1.12-2.11). Among patients with an R0 resection, margin width was also
      associated with RFS (1-4 mm: HR 1.32, 95 % CI 0.98-1.78 vs. 5-9 mm: HR 1.21, 95 %
      CI 0.89-1.66) and OS (1-4 mm: HR 1.95, 95 % CI 0.45-2.63 vs. 5-9 mm: HR 1.21, 95
      % CI 0.88-1.68) (referent >=1 cm; both p <= 0.002). Margin status and width
      remain independently associated with RFS and OS on multivariable analyses.
      CONCLUSIONS: For patients undergoing resection of ICC, R1 margin status was
      associated with an inferior long-term outcome. Moreover, there was an incremental
      worsening RFS and OS as margin width decreased.

PMID- 25762482
TI  - Prospective Evaluation of Zoledronic Acid in the Treatment of Bone Metastases
      from Differentiated Thyroid Carcinoma.
AB  - PURPOSE: The objectives of this study were to prospectively delineate the
      efficacy and safety of zoledronic acid for treating bone metastases (BM) from
      differentiated thyroid carcinoma (DTC), and to evaluate the relationships between
      levels of bone metabolic markers and occurrence of skeletal-related events
      (SREs). METHODS: This was a prospective, single-arm, single-center study.
      Nineteen patients with BM from DTC were assigned to receive zoledronic acid
      therapy every 4-5 weeks. Imaging studies for sites of BM were conducted every 6
      months, and levels of bone metabolic markers, including serum bone-specific
      alkaline phosphatase (BAP) and urinary N-telopeptide of type I collagen (NTx),
      were assessed every 3 months. To evaluate the efficacy of zoledronic acid use,
      data of SREs were compared with those of 16 historical controls. RESULTS: SREs
      developed in eight patients (42 %), but metastatic spinal cord compression (MSCC)
      appeared in only one patient. Pain scores were ameliorated in five patients, but
      aggravated in six patients. Ten patients had stable disease, six showed
      progressive disease, and none showed partial or complete response during the
      observation period. Decreases in levels of bone metabolic markers were observed
      in ten patients for BAP and 15 for NTx. However, no significant correlations were
      identified between changes in bone metabolic marker levels and development of
      SREs. CONCLUSIONS: Zoledronic acid may offer a mainstay of multidisciplinary
      treatment for patients with BM for the purpose of reducing SREs. Levels of serum
      BAP and urinary NTx do not appear reliable as indicators of amelioration of BM
      symptoms.

PMID- 25762483
TI  - Corrigendum: recrystallization and grain growth induced by ELMs-like transient
      heat loads in deformed tungsten samples.

PMID- 25762485
TI  - A high-mobility electronic system at an electrolyte-gated oxide surface.
AB  - Electrolyte gating is a powerful technique for accumulating large carrier
      densities at a surface. Yet this approach suffers from significant sources of
      disorder: electrochemical reactions can damage or alter the sample, and the ions
      of the electrolyte and various dissolved contaminants sit Angstroms from the
      electron system. Accordingly, electrolyte gating is well suited to studies of
      superconductivity and other phenomena robust to disorder, but of limited use when
      reactions or disorder must be avoided. Here we demonstrate that these limitations
      can be overcome by protecting the sample with a chemically inert, atomically
      smooth sheet of hexagonal boron nitride. We illustrate our technique with
      electrolyte-gated strontium titanate, whose mobility when protected with boron
      nitride improves more than 10-fold while achieving carrier densities nearing
      10(14) cm(-2). Our technique is portable to other materials, and should enable
      future studies where high carrier density modulation is required but
      electrochemical reactions and surface disorder must be minimized. 

PMID- 25762484
TI  - Protein traffic disorders: an effective high-throughput fluorescence microscopy
      pipeline for drug discovery.
AB  - Plasma membrane proteins are essential molecules in the cell which mediate
      interactions with the exterior milieu, thus representing key drug targets for
      present pharma. Not surprisingly, protein traffic disorders include a large range
      of diseases sharing the common mechanism of failure in the respective protein to
      reach the plasma membrane. However, specific therapies for these diseases are
      remarkably lacking. Herein, we report a robust platform for drug discovery
      applied to a paradigmatic genetic disorder affecting intracellular trafficking -
      Cystic Fibrosis. This platform includes (i) two original respiratory epithelial
      cellular models incorporating an inducible double-tagged traffic reporter; (ii) a
      plasma membrane protein traffic assay for high-throughput microscopy screening;
      and (iii) open-source image analysis software to quantify plasma membrane protein
      traffic. By allowing direct scoring of compounds rescuing the basic traffic
      defect, this platform enables an effective drug development pipeline, which can
      be promptly adapted to any traffic disorder-associated protein and leverage
      therapy development efforts. 

PMID- 25762486
TI  - Single-Session CT-Guided Percutaneous Microwave Ablation of Bilateral Adrenal
      Gland Hyperplasia Due to Ectopic ACTH Syndrome.
AB  - Bilateral adrenalectomy is currently the only available treatment for
      adrenocorticotropic hormone (ACTH)-dependent Cushing's syndrome (ectopic ACTH
      syndrome) that is refractory to pharmacologic therapy. We describe two patients
      with refractory ectopic ACTH syndrome who were treated with CT-guided
      percutaneous microwave ablation of both hyperplastic adrenal glands in a single
      session: O ne was not a surgical candidate, and the other had undergone
      unsuccessful surgery. Following the procedure, both patients achieved substantial
      decreases in serum cortisol, symptomatic improvement, and decreased anti
      hypertensive medication requirements. 

PMID- 25762487
TI  - Hepatic Tract Plug-Embolisation After Biliary Stenting. Is It Worthwhile?
AB  - PURPOSE: PTC and stenting procedures are associated with significant risks
      including life-threatening haemorrhage, sepsis, renal failure and high mortality
      rates. PTC tract closure methods are utilised to reduce haemorrhagic
      complications despite little evidence to support their use. The current study
      assesses the incidence of haemorrhagic complications following PTC and stenting
      procedures, both prior to and following the introduction of a dedicated expanding
      gelatin foam-targeted embolisation liver tract closure technique. MATERIALS AND
      METHODS: Haemorrhagic complications were retrospectively identified in patients
      undergoing PTC procedures both prior to (subgroup 1) and following (subgroup 2)
      the introduction of a dedicated targeted liver tract closure method between
      9/11/2010 and 10/08/2012 in a single tertiary referral centre. Mean blood Hb
      decrease following PTC was established in subgroups 1 and 2. Kaplan-Meier life
      table analysis was performed to compare survival outcomes between subgroups using
      the log-rank test. RESULTS: Haemorrhagic complications were significantly reduced
      following the introduction of the targeted PTC tract closure method [(12 vs. 3 %
      of subgroups 1 (n = 101) and 2 (n = 92), respectively (p = 0.027)]. Mean blood Hb
      decrease following PTC was 1.40 versus 0.68 g/dL in subgroups 1 and 2,
      respectively (p = 0.069). 30-day mortality was 14 and 12 % in subgroups 1 and 2,
      respectively. 50 % of the entire cohort had died by 174 days post-PTC.
      CONCLUSION: Introduction of liver tract embolisation significantly reduced
      haemorrhagic complications in our patient cohort. Utilisation of this method has
      the potential to reduce the morbidity and mortality burden associated with post
      PTC haemorrhage by preventing bleeding from the liver access tract.

PMID- 25762488
TI  - The retrograde transvenous push-through method: a novel treatment of peripheral
      arteriovenous malformations with dominant venous outflow.
AB  - PURPOSE: To evaluate the efficacy and safety of a novel retrograde transvenous
      embolization technique of peripheral arteriovenous malformations (AVMs) using
      Onyx. MATERIALS AND METHODS: We conducted a retrospective analysis of all
      patients who underwent transvenous retrograde Onyx embolization of peripheral
      AVMs with dominant venous outflow over a 29-month period. The embolization is
      aimed at retrograde filling of the nidus after building a solid plug in the
      dominant venous outflow (push-through). Classification, clinical signs, technical
      aspects, clinical and technical success rates, and complications were recorded.
      Short-term outcome was assessed. RESULTS: 11 Symptomatic patients (8 female; mean
      age 31.4 years) were treated at our Vascular Anomalies Center with this method
      between January 2012 and May 2014. The AVMs were located on the upper extremity
      (n = 3), pelvis (n = 2), buttock (n = 2), and lower extremity (n = 4). Retrograde
      embolization was successfully carried out after preparatory transarterial-flow
      reduction in eight cases (73 %) and venous-flow reduction with Amplatzer Vascular
      Plugs in four cases (36 %). Complete devascularization (n = 10; 91 %) or 95 %
      devascularization (n = 1; 9 %) led to complete resolution (n = 8; 73 %) or
      improvement of clinical symptoms (n = 3; 27 %). One minor complication occurred
      (pain and swelling). During a mean follow-up time of 8 months, one clinically
      asymptomatic recurrence of AVM was detected. CONCLUSION: Initial results suggest
      that retrograde transvenous Onyx embolization of peripheral AVMs with dominant
      venous outflow is a safe and effective novel technique with a low complication
      rate.

PMID- 25762489
TI  - Serostatus following live attenuated vaccination administered before pediatric
      liver transplantation.
AB  - After liver transplantation (LT), live attenuated vaccines (LAVs) are generally
      contraindicated. LAVs are recommended before LT for patients >= 6 months of age.
      However, the evidence supporting this practice is limited. Patients were enrolled
      before and after LT. Clinical data for patients were obtained from medical
      records. Serum antibody titers were evaluated at the time of enrollment and
      prospectively. Serum antibody titers were measured with a hemagglutination
      inhibition test for measles and rubella and with an enzyme-linked immunosorbent
      assay for varicella and mumps. Univariate and multivariate analyses were
      performed to investigate the factors that affect the serostatus. Serological
      analyses of 49 patients immunized before LT (median age, 45 months; male, 35%)
      were performed. Underlying diseases were biliary atresia (n = 27; 55%), metabolic
      diseases (n = 13; 27%), fulminant hepatic failure (n = 5; 10%), and others (n =
      4; 8%). The seropositivity rate after each vaccine was 46.9% (measles), 89.4%
      (rubella), 67.5% (varicella), and 48.8% (mumps). Factors independently associated
      with seronegativity were a vaccination age < 12 months for measles (P = .002), a
      lower body weight for varicella (P = 0.01), and underlying diseases other than
      biliary atresia for mumps (P = .004). No serious adverse event was observed
      during the study period. The immunogenicity of LAVs before LT was high for
      rubella but low for the others. Before LT, further vaccination strategies are
      needed for patients. In addition, serological follow-up may be indicated for
      patients with factors associated with seronegativity.

PMID- 25762491
TI  - Metaphor creates intimacy and temporarily enhances theory of mind.
AB  - In 3 experiments we show that, relative to reading literal sentences, reading
      metaphor enhances performance on the Reading the Mind in the Eyes Test (RMET), an
      instrument meant to measure first-order theory of mind. In each experiment
      participants read metaphorical or literal sentences in different contexts and
      afterwards completed an ostensibly unrelated task, the RMET. In Experiment 1,
      participants were presented metaphorical or literal sentences in short discourse
      contexts and were asked questions about the characters in the stories. We found
      that when one of the characters used metaphor, they were rated as having a closer
      relationship. A novel finding is that the degree to which the characters are
      perceived as being more intimate in the metaphor condition, the higher their
      scores on the RMET. In Experiment 2, participants created fictive contexts to
      prompting literal or metaphorical sentences. This writing task was followed by
      the RMET. Participants who created contexts for the metaphors scored
      significantly higher on the RMET. In Experiment 3, participants read metaphors or
      literal counterparts without any discourse contexts. Once again, participants
      scored higher on the RMET after reading metaphorical as opposed to literal
      sentences. Additional analyses across the 3 experiments revealed that metaphors
      but not literal counterparts were associated with fictive contexts that contained
      reference to mental states and idioms with emotional content (Experiment 2), were
      associated with a sense of intimacy between interlocutors (Experiment 1), the
      presence of affective words in the created context (Experiment 2), and
      association with a human agent when context was not presented (Experiment 3). 

PMID- 25762490
TI  - SUMO2 overexpression enhances the generation and function of interleukin-17
      producing CD8+ T cells in mice.
AB  - Small ubiquitin-like modifier (SUMO) 2 is a small protein that controls the
      activity and stability of other proteins by SUMOylation. In this study, T cell
      specific SUMO2 overexpressing transgenic mice were generated to study the effect
      of SUMO2 on T lymphocytes. SUMO2 overexpression promoted differentiation of
      interleukin (IL)-17-producing CD8(+) T cells, and significantly suppressed the
      growth of EL4 tumor cells in vivo. Moreover, the tumor tissue from SUMO2
      overexpressing mice had higher interferon (IFN)-gamma and granzyme B mRNA levels.
      Although SUMO2 overexpression did not increase IFN-gamma or granzyme B production
      in cytotoxic T lymphocytes, IL-12 treatment restored and increased IFN-gamma
      secretion in IL-17-producing CD8(+) T cells. SUMO2 overexpression also increased
      gene expression of chemokines, CCL4, and CXCL10, which attract cytotoxic T
      lymphocytes to tumor tissues. Additionally, SUMO2-overexpressing T cells
      exhibited increased STAT3 phosphorylation, implying a SUMO2 target which up
      regulates STAT3 activity governing IL-17A-producing CD8(+) T cell differentiation
      and antitumor immune responses. 

PMID- 25762492
TI  - Glutaric Acidemia Type 1-Clinico-Molecular Profile and Novel Mutations in GCDH
      Gene in Indian Patients.
AB  - Glutaric acidemia I (GA I, #231670) is one of the treatable, autosomal
      recessively inherited metabolic disorders. Macrocephaly, acute encephalitis-like
      crises, dystonia and characteristic frontotemporal atrophy are the hallmarks of
      this disease. In this communication, we present the clinical, biochemical and
      molecular profile of seventeen GA I patients from 15 unrelated families from
      India and report seven novel mutations in GCDH gene (c.281G>A (p.Arg94Gln),
      c.401A>G (p.Asp134Gly), c.662T>C (p.Leu221Pro), c.881G>C (p.Arg294Pro),
      c.1173dupG (p.Asn392Glufs*5), c.1238A>G (p.Tyr413Cys) and c.1241A>C
      (p.Glu414Ala)). Out of these, c.662T>C (p.Leu221Pro) in exon 8 and c.281G>A
      (p.Arg94Gln) allele in exon 4 were low excretor alleles, whereas c.1241A>C
      (p.Glu414Ala), c.1173dupG and c.1207C>T (p.His403Tyr) in exon 11 were high
      excretor alleles. We conclude that c.1204C>T (p.Arg402Trp) is probably the most
      common mutant allele. Exons 11 and 8 are the hot spot regions of GCDH gene in
      Indian patients with GA I. An early diagnosis and timely intervention can improve
      the underlying prognosis. Molecular confirmation is helpful in providing genetic
      counselling and prenatal diagnosis in subsequent pregnancy. 

PMID- 25762493
TI  - Audit of the Use of Regular Haem Arginate Infusions in Patients with Acute
      Porphyria to Prevent Recurrent Symptoms.
AB  - The National Acute Porphyria Service (NAPS) provides acute care support and
      clinical advice for patients in England with active acute porphyria requiring
      haem arginate treatment and patients with recurrent acute attacks.This audit
      examined the benefits and complications of regular haem arginate treatment
      started with prophylactic intent to reduce the frequency of recurrent acute
      attacks in a group of patients managed through NAPS. We included 22 patients (21
      female and 1 male) and returned information on diagnosis, indications for
      prophylactic infusions, frequency and dose, analgesia, activity and employment
      and complications including thromboembolic disease and iron overload.The median
      age at presentation with porphyria was 21 years (range 9-44), with acute
      abdominal pain as the predominant symptom. Patients had a median of 12 (1-400)
      attacks before starting prophylaxis and had received a median of 52 (0-1,350)
      doses of haem arginate. The median age at starting prophylaxis was 28 years (13
      58) with a median delay of 4 years (0.5-37) between presentation and prophylaxis.
      The frequency of prophylactic haem arginate varied from 1 to 8 per month, and 67%
      patients were documented as having a reduction in pain frequency on prophylaxis.
      Only one patient developed clinically significant iron overload and required iron
      chelation, but the number of venous access devices required varied from 1 to 15,
      with each device lasting a median of 1.2 years before requiring replacement. Six
      patients stopped haem arginate and in three this was because their symptoms had
      improved. Prophylactic haem arginate appears to be beneficial in patients with
      recurrent acute porphyria symptoms, but maintaining central venous access may
      prove challenging. 

PMID- 25762494
TI  - Normal Cerebrospinal Fluid Pyridoxal 5'-Phosphate Level in a PNPO-Deficient
      Patient with Neonatal-Onset Epileptic Encephalopathy.
AB  - Deficiency of pyridox(am)ine 5'-phosphate oxidase (PNPO, OMIM 610090) is a
      treatable autosomal recessive inborn error of metabolism. Neonatal epileptic
      encephalopathy and a low cerebrospinal fluid (CSF) pyridoxal 5'-phosphate level
      are the reported hallmarks of PNPO deficiency, but its clinical and biochemical
      spectra are not fully known. CASE PRESENTATION: A girl born at 33 3/7 weeks of
      gestation developed seizures in the first hours of life. Her seizures initially
      responded to GABAergic agonists, but she subsequently developed a severe
      epileptic encephalopathy. Brain MRI and infectious and metabolic evaluations at
      birth, including urinary alpha-aminoadipic semialdehyde (AASA), were normal.
      Lumbar puncture at age 3 months showed: pyridoxal 5'-phosphate, 52 nmol/L
      (normal, 23-64); homovanillic acid, 392 nmol/L (normal, 450-1,132); 5
      hydroxyindoleacetic acid, 341 nmol/L (normal, 179-711); and 3-ortho-methyldopa,
      30 nmol/L (normal, below 300). The patient was not being treated with pyridoxine
      nor with pyridoxal 5'-phosphate at the time of the lumbar puncture. She died at
      age 14 months. A sequencing panel targeting 53 epilepsy-related genes revealed a
      homozygous missense mutation in PNPO (c.674G>A, p.R225H). Homozygosity was
      confirmed by parental testing. Expression studies of mutant p.R225H PNPO revealed
      greatly reduced activity. In conclusion, a normal CSF level of pyridoxal 5'
      phosphate does not rule out PNPO deficiency.

PMID- 25762495
TI  - Age at First Cardiac Symptoms in Fabry Disease: Association with a Chinese
      Hotspot Fabry Mutation (IVS4+919G>A), Classical Fabry Mutations, and Sex in a
      Taiwanese Population from the Fabry Outcome Survey (FOS).
AB  - This is a descriptive analysis of a cohort of 59 Taiwanese patients with Fabry
      disease and either classical Fabry or cardiac variant IVS4+919G>A (IVS4)
      mutations from a disease registry, the Fabry Outcome Survey (FOS; sponsored by
      Shire). Most of our classical Fabry patients were symptomatic and were identified
      upon seeking medical advice at our clinics, whereas most of our IVS4 patients
      attended our clinics after newborn screening identified this mutation in their
      grandsons. The objective was to determine differences in cardiac manifestations
      between patients with classical Fabry or IVS4 mutations by comparing age at onset
      of selected cardiac symptoms. Data were extracted in August 2013 and analyzed
      retrospectively. Fifty-nine Taiwanese patients (median age at extract 60.7 years
      [range 15.0-86.9]; n = 36 [61%] male) with proven IVS4 (n = 41 [69%]) or
      classical Fabry mutations (n = 18 [31%]) had available data on cardiac symptoms.
      Of 55 (93%) patients with reported left ventricular hypertrophy (LVH), mean [SD]
      age (years) at first symptom was lower in classical Fabry males (30.0 [15.1]; n =
      4) than classical Fabry females (49.6 [8.9]; n = 11; p < 0.05), but not in IVS4
      females (57.4 [13.7]; n = 10) compared with IVS4 males (55.9 [11.3]; n = 30).
      Mean age at first LVH diagnosis was significantly lower in classical Fabry males
      versus IVS4 males (p < 0.05). No significant difference in age at onset of
      arrhythmia or conductive abnormality, chest pain, or palpitations or cardiac
      syncope was found between the groups. The most noteworthy finding of this study
      is the lack of a significant gender sex difference in age at onset of cardiac
      symptoms in IVS4 patients. 

PMID- 25762496
TI  - Elemental Analysis of Variably Contaminated Cremains Using X-ray Fluorescence
      Spectrometry.
AB  - Analyzing and identifying skeletal remains becomes increasingly difficult when
      remains have been cremated, especially in cases where the cremated material may
      have been intentionally contaminated with nonskeletal material. This study
      examined the potential of X-ray fluorescence spectrometry (XRF) to detect the
      presence of nonskeletal contaminants in samples of cremains. Eleven samples of
      cremains were variably combined with concrete mix and analyzed using XRF. Photon
      counts of elements in each sample were analyzed, and the coefficient of
      determination (R(2)) using unweighted linear regression as a function of percent
      cremains was calculated. Results showed that with changes in the proportion of
      skeletal material and contaminant, there were significant (R(2) > 0.90) changes
      in detected levels of phosphorus, potassium, zinc, aluminum, and sulfur. The use
      of XRF is concluded to be a valid approach in the identification of the presence
      of nonskeletal material in potentially contaminated cremains.

PMID- 25762497
TI  - Recent applications of UHF-MRI in the study of human brain function and
      structure: a review.
AB  - The increased availability of ultra-high-field (UHF) MRI has led to its
      application in a wide range of neuroimaging studies, which are showing promise in
      transforming fundamental approaches to human neuroscience. This review presents
      recent work on structural and functional brain imaging, at 7 T and higher field
      strengths. After a short outline of the effects of high field strength on MR
      images, the rapidly expanding literature on UHF applications of blood-oxygenation
      level-dependent-based functional MRI is reviewed. Structural imaging is then
      discussed, divided into sections on imaging weighted by relaxation time,
      including quantitative relaxation time mapping, phase imaging and quantitative
      susceptibility mapping, angiography, diffusion-weighted imaging, and finally
      magnetization-transfer imaging. The final section discusses studies using the
      high spatial resolution available at UHF to identify explicit links between
      structure and function. Copyright (c) 2015 John Wiley & Sons, Ltd.

PMID- 25762498
TI  - Multiple strategies of oxygen supply in Drosophila malignancies identify
      tracheogenesis as a novel cancer hallmark.
AB  - Angiogenesis is the term used to describe all the alterations in blood vessel
      growth induced by a tumour mass following hypoxic stress. The occurrence of
      multiple strategies of vessel recruitment favours drug resistance, greatly
      complicating the treatment of certain tumours. In Drosophila, oxygen is conveyed
      to the internal organs by the tracheal system, a closed tubular network whose
      role in cancer growth is so far unexplored. We found that, as observed in human
      cancers, Drosophila malignant cells suffer from oxygen shortage, release pro
      tracheogenic factors, co-opt nearby vessels and get incorporated into the
      tracheal walls. We also found that the parallelisms observed in cellular
      behaviours are supported by genetic and molecular conservation. Finally, we
      identified a molecular circuitry associated with the differentiation of cancer
      cells into tracheal cells. In summary, our findings identify tracheogenesis as a
      novel cancer hallmark in Drosophila, further expanding the power of the fly model
      in cancer research. 

PMID- 25762500
TI  - Classical eye signs in bacterial endocarditis.

PMID- 25762499
TI  - Efficacy of pastes containing CPP-ACP and CPP-ACFP in patients with Sjogren's
      syndrome.
AB  - OBJECTIVES: The purpose of this study was to evaluate efficacy of casein
      phosphopeptide-amorphous calcium phosphate (CPP-ACP) and casein phosphopeptide
      amorphous calcium fluoride phosphate (CPP-ACFP) containing pastes among
      individuals with Sjogren's syndrome (SS). MATERIALS AND METHODS: Thirty patients
      were randomised into three groups: CPP-ACP, CPP-ACFP, and 0.05 % NaF to be used
      two times a day during a 28-day experimental period. Saliva was analysed for flow
      rate, pH, buffering capacity and mineral concentrations. Dental plaque was
      examined for pH. Following the formation of artificial carious lesion,
      participants wore enamel slabs for an in situ remineralisation study.
      Remineralisation potential was examined using scanning electron microscope (SEM)
      and energy dispersive spectroscopic (EDS) technique. SE microphotographs were
      subsequently analysed for area, diameter, perimeter, roundness and the number of
      enamel defects and percentage of tooth surface affected by defects. RESULTS: At
      the end of the experimental period, a slight increase of salivary pH could have
      been observed. No differences in mineral composition of saliva were noted. The
      use of CPP-ACP and CPP-ACFP contributed to a significant rise of plaque pH. Image
      analysis revealed excessive reduction of defects' dimensions in the three
      experimental groups, and a decrease of the number of enamel defects in the CPP
      ACP and CPP-ACFP groups. The EDS analysis did not show differences in Ca/P, Ca/O
      and P/O ratios in any of the treatment groups. CONCLUSION: CPP-ACP and CPP-ACFP
      hold promise as remineralising agents for patients with SS. CLINICAL RELEVANCE:
      Pastes containing CPP-ACP/CPP-ACFP show enhanced remineralisation potential
      compared with NaF mouthrinse in patients with SS.

PMID- 25762501
TI  - Inflammation and ER stress downregulate BDH2 expression and dysregulate
      intracellular iron in macrophages.
AB  - Macrophages play a very important role in host defense and in iron homeostasis by
      engulfing senescent red blood cells and recycling iron. Hepcidin is the master
      iron regulating hormone that limits dietary iron absorption from the gut and
      limits iron egress from macrophages. Upon infection macrophages retain iron to
      limit its bioavailability which limits bacterial growth. Recently, a short chain
      butyrate dehydrogenase type 2 (BDH2) protein was reported to contain an iron
      responsive element and to mediate cellular iron trafficking by catalyzing the
      synthesis of the mammalian siderophore that binds labile iron; therefore, BDH2
      plays a crucial role in intracellular iron homeostasis. However, BDH2 expression
      and regulation in macrophages have not yet been described. Here we show that LPS
      induced inflammation combined with ER stress led to massive BDH2 downregulation,
      increased the expression of ER stress markers, upregulated hepcidin expression,
      downregulated ferroportin expression, caused iron retention in macrophages, and
      dysregulated cytokine release from macrophages. We also show that ER stress
      combined with inflammation synergistically upregulated the expression of the iron
      carrier protein NGAL and the stress-inducible heme degrading enzyme heme
      oxygenase-1 (HO-1) leading to iron liberation. This is the first report to show
      that inflammation and ER stress downregulate the expression of BDH2 in human THP
      1 macrophages. 

PMID- 25762502
TI  - Genome wide expression profiling of p53 regulated miRNAs in neuroblastoma.
AB  - Restoration of the antitumor activity of p53 could offer a promising approach for
      the treatment of neuroblastoma. MicroRNAs (miRNAs) are important mediators of p53
      activity, but their role in the p53 response has not yet been comprehensively
      addressed in neuroblastoma. Therefore, we set out to characterize alterations in
      miRNA expression that are induced by p53 activation in neuroblastoma cells.
      Genome-wide miRNA expression analysis showed that miR-34a-5p, miR-182-5p, miR
      203a, miR-222-3p, and miR-432-5p are upregulated following nutlin-3 treatment in
      a p53 dependent manner. The function of miR-182-5p, miR-203a, miR-222-3p, and miR
      432-5p was analyzed by ectopic overexpression of miRNA mimics. We observed that
      these p53-regulated miRNAs inhibit the proliferation of neuroblastoma cells to
      varying degrees, with the most profound growth inhibition recorded for miR-182
      5p. Overexpression of miR-182-5p promoted apoptosis in some neuroblastoma cell
      lines and induced neuronal differentiation of NGP cells. Using Chromatin
      Immunoprecipitation-qPCR (ChIP-qPCR), we did not observe direct binding of p53 to
      MIR182, MIR203, MIR222, and MIR432 in neuroblastoma cells. Taken together, our
      findings yield new insights in the network of p53-regulated miRNAs in
      neuroblastoma. 

PMID- 25762504
TI  - Micro-trace fossils reveal pervasive reworking of Pliocene sapropels by low
      oxygen-adapted benthic meiofauna.
AB  - Animal burrowers leave an indelible signature on the sedimentary record in most
      marine environments, with the seeming exception of low-oxygen environments. In
      modern sedimentary settings, however, sub-millimetre-sized benthic animals
      (meiofauna) are adapted to low oxygen and even sulfidic conditions. Almost
      nothing is known about their impact on ancient marine sediments because they
      leave few recognizable traces. Here we show, in classic Pliocene-aged anoxic
      facies from the Mediterranean, the first reported trace fossil evidence of
      meiofaunal activity and its relation to changing oxygenation. A novel approach
      utilizing electron imaging of ion-polished samples shows that meiofauna
      pervasively reworked sediment under oxygen-depleted conditions that excluded
      macrofauna, fragmenting organic laminae and emplacing 15- to 70-MUm-diameter
      faecal pellets without macroscopically influencing the fabric. The extent of
      reworking raises the question: how pervasively altered are other sediments
      presently assumed to lack animal influence and how far into the geological record
      does this influence extend? 

PMID- 25762505
TI  - Ultrasound-guided supraclavicular block in a patient with no first rib.

PMID- 25762503
TI  - Mesenchymal stem cells in the treatment of type 1 diabetes mellitus.
AB  - Diabetes mellitus type 1 is a form of diabetes mellitus that results from the
      autoimmune destruction of insulin-producing beta cells in the pancreas. The
      current gold standard therapy for pancreas transplantation has limitations
      because of the long list of waiting patients and the limited supply of donor
      pancreas. Mesenchymal stem cells (MSCs), a relatively new potential therapy in
      various fields, have already made their mark in the young field of regenerative
      medicine. Recent studies have shown that the implantation of MSCs decreases
      glucose levels through paracrine influences rather than through direct
      transdifferentiation into insulin-producing cells. Therefore, these cells may use
      pro-angiogenic and immunomodulatory effects to control diabetes following the
      cotransplantation with pancreatic islets. In this review, we present and discuss
      new approaches of using MSCs in the treatment of diabetes mellitus type 1. 

PMID- 25762506
TI  - STAQ: A route toward low power, multicolor nanoscopy.
AB  - Nanoscopy has now become a real procedure in fluorescence microscopy of living
      cells. The STED/RESOLFT family of nanoscopy approaches has the best prospects for
      delivering high speed imaging, but the history of STED includes a continuing
      struggle to reduce the deactivation power applied, along with difficulties in
      achieving simultaneous multicolor images. In this manuscript, we present a
      concept for a similar real-time nanoscopy, using a new class of bipartite probes
      that separate the luminescent and quenching functions into two coupled molecules.
      In particular, the STAQ (Superresolution via Transiently Activated Quencher)
      example we show herein employs the excited state absorbance (not ground state) of
      the partner to accept energy from and quench the luminescent dye. The result is
      that much less deactivation power is needed for superresolved (~50 nm) imaging.
      Moreover, the TAQ partner excited by the "donut" beam is shown to quench several
      different visible dyes via the same mechanism, opening the door to easier
      multicolor imaging. We demonstrate three dyes sharing the same deactivation and
      show examples of superresolved multicolor images. We suggest STAQ will facilitate
      the growth of real-time nanoscopy by reducing confounding photodamage within
      living cells while expanding the nanoscopist's palette.

PMID- 25762507
TI  - Failure to look beyond blocks is a mistake.
AB  - Tamm and Hilgers are to be congratulated for bringing more attention to a rather
      important issue in trial design, namely chronological bias. Far too many
      researchers use permuted blocks without even recognizing that chronological bias
      is the reason they do it. Only armed with the rationale can we hope to enter an
      informed discussion regarding the merits, or lack thereof, for using permuted
      block randomization in actual trials. But chronological bias is only part of the
      story. If it were the entire story, then there would be a rather easy solution.
      We could just use blocks of size two, or even alternate treatment groups. But we
      can't, and the reason we can't is selection bias. The two are at odds, as the
      solution to chronological bias is a small block size, and the solution to
      selection bias is a large block size. At least this would be the case if we were
      limited to using permuted blocks. Fortunately, we are not.

PMID- 25762509
TI  - STEP: Self-supporting tailored k-space estimation for parallel imaging
      reconstruction.
AB  - PURPOSE: A new subspace-based iterative reconstruction method, termed Self
      supporting Tailored k-space Estimation for Parallel imaging reconstruction
      (STEP), is presented and evaluated in comparison to the existing autocalibrating
      method SPIRiT and calibrationless method SAKE. THEORY AND METHODS: In STEP, two
      tailored schemes including k-space partition and basis selection are proposed to
      promote spatially variant signal subspace and incorporated into a self-supporting
      structured low rank model to enforce properties of locality, sparsity, and rank
      deficiency, which can be formulated into a constrained optimization problem and
      solved by an iterative algorithm. Simulated and in vivo datasets were used to
      investigate the performance of STEP in terms of overall image quality and detail
      structure preservation. RESULTS: The advantage of STEP on image quality is
      demonstrated by retrospectively undersampled multichannel Cartesian data with
      various patterns. Compared with SPIRiT and SAKE, STEP can provide more accurate
      reconstruction images with less residual aliasing artifacts and reduced noise
      amplification in simulation and in vivo experiments. In addition, STEP has the
      capability of combining compressed sensing with arbitrary sampling trajectory.
      CONCLUSION: Using k-space partition and basis selection can further improve the
      performance of parallel imaging reconstruction with or without calibration
      signals.

PMID- 25762508
TI  - A quasi-experimental design to assess the effectiveness of the federal healthy
      start in reducing preterm birth among obese mothers.
AB  - We assessed the impact of Central Hillsborough Healthy Start (CHHS), a federally
      funded program dedicated to improving maternal and infant outcomes in a
      population of high-risk obese mothers in the socio-economically challenged
      community of East Tampa in Florida on preterm birth and very preterm birth
      (VPTB). We utilized hospital discharge records linked to vital statistics data in
      Florida (2004-2007) to study obese women with a singleton birth, matching mothers
      in the CHHS catchment area with those from the rest of Florida. We conducted
      conditional logistic regression with the matched data. Obese mothers in the CHHS
      service area had a 61% lower likelihood of having a VPTB infant than obese
      mothers in the rest of the state (AOR = 0.39, 95% CI 0.21-0.70). Obese women of
      reproductive age may benefit from services from federal Healthy Start programs.
      Study findings underscore the need for further research to explore the impact of
      such programs.

PMID- 25762510
TI  - RC/BTB2 is essential for formation of primary cilia in mammalian cells.
AB  - RC/BTB2 is a binding partner of sperm associated antigen 16S (SPAG16S), which is
      a regulator of spermiogenesis in mice, a process during which sperm flagella are
      formed. The expression of Rc/btb2 is also regulated by multicilin, a protein that
      controls ciliogenesis. Given that mouse Rc/btb2 mRNA is not only expressed in
      tissues bearing motile cilia, but also in tissues without motile cilia, we
      investigated whether RC/BTB2 plays a role in the general process of ciliogenesis
      by studying two cell lines that have primary cilia, NIH3T3, and IMCD3. We
      discovered that the subcellular localization of RC/BTB2 in the NIH3T3 and IMCD3
      cells encompasses the pathway for ciliogenesis. RC/BTB2 was found in the Golgi
      bodies and centrosomes, two key structures essential for normal ciliogenesis.
      Knockdown of Rc/btb2 gene expression in these cell lines disrupted ciliogenesis.
      The percentage of cells with primary cilia was significantly reduced in stable
      cell lines transduced with specific Rc/btb2 shRNA viruses as compared to the
      control cells. When cilia were formed in the knockdown cells, they were
      significantly shorter than those in the control cells. Knockdown of Rc/btb2
      expression did not affect cell proliferation and the cell cycle. Exogenous
      expression of RC/BTB2 in these stable knockdown cells restored ciliogenesis.
      These findings suggest that RC/BTB2 is a necessary component of the process of
      formation of primary cilia in somatic cells, perhaps through the transportation
      of cargos from Golgi bodies to centrosomes for cilia assembling.

PMID- 25762511
TI  - In vivo X-ray elemental imaging of single cell model organisms manipulated by
      laser-based optical tweezers.
AB  - We report on a radically new elemental imaging approach for the analysis of
      biological model organisms and single cells in their natural, in vivo state. The
      methodology combines optical tweezers (OT) technology for non-contact, laser
      based sample manipulation with synchrotron radiation confocal X-ray fluorescence
      (XRF) microimaging for the first time. The main objective of this work is to
      establish a new method for in vivo elemental imaging in a two-dimensional (2D)
      projection mode in free-standing biological microorganisms or single cells,
      present in their aqueous environment. Using the model organism Scrippsiella
      trochoidea, a first proof of principle experiment at beamline ID13 of the
      European Synchrotron Radiation Facility (ESRF) demonstrates the feasibility of
      the OT XRF methodology, which is applied to study mixture toxicity of Cu-Ni and
      Cu-Zn as a result of elevated exposure. We expect that the new OT XRF methodology
      will significantly contribute to the new trend of investigating microorganisms at
      the cellular level with added in vivo capability. 

PMID- 25762512
TI  - Industry influence moved focus of US dental research away from sugar, documents
      indicate.

PMID- 25762513
TI  - ERRATUM: Tet1-mediated DNA demethylation regulates neuronal cell death induced by
      oxidative stress.

PMID- 25762514
TI  - Structure of p15(PAF)-PCNA complex and implications for clamp sliding during DNA
      replication and repair.
AB  - The intrinsically disordered protein p15(PAF) regulates DNA replication and
      repair by binding to the proliferating cell nuclear antigen (PCNA) sliding clamp.
      We present the structure of the human p15(PAF)-PCNA complex. Crystallography and
      NMR show the central PCNA-interacting protein motif (PIP-box) of p15(PAF) tightly
      bound to the front-face of PCNA. In contrast to other PCNA-interacting proteins,
      p15(PAF) also contacts the inside of, and passes through, the PCNA ring. The
      disordered p15(PAF) termini emerge at opposite faces of the ring, but remain
      protected from 20S proteasomal degradation. Both free and PCNA-bound p15(PAF)
      binds DNA mainly through its histone-like N-terminal tail, while PCNA does not,
      and a model of the ternary complex with DNA inside the PCNA ring is consistent
      with electron micrographs. We propose that p15(PAF) acts as a flexible drag that
      regulates PCNA sliding along the DNA and facilitates the switch from replicative
      to translesion synthesis polymerase binding. 

PMID- 25762515
TI  - The value of serum mean platelet volume in testicular torsion.
AB  - OBJECTIVE: To compare the serum mean platelet volume (MPV) in patients with
      testicular torsion and healthy control subjects. METHODS: This retrospective
      study compared clinical and demographic data from patients who underwent surgery
      for testicular torsion and healthy controls. Testicular torsion was diagnosed
      with a physical examination and Doppler ultrasonography. Age, leukocyte count,
      platelet count and MPV were recorded for all participants. RESULTS: A total of 50
      patients with testicular torsion and 51 healthy control subjects were enrolled.
      There was no significant difference in age and platelet count between the two
      groups. Patients with testicular torsion had a significantly higher leukocyte
      count and MPV, compared with controls. According to receiver operating
      characteristic curve analysis performed for the prediction of testicular torsion,
      the best cut-off point for MPV was 7.7 fl (sensitivity 62%, specificity 96%), and
      the best cut-off point for leukocyte count was 9.5 * 10(9)/l (sensitivity 58%,
      specificity 80%). CONCLUSIONS: The MPV may be useful as an ancillary test for the
      diagnosis of testicular torsion. Further studies are needed in order to confirm
      these preliminary results.

PMID- 25762516
TI  - Characteristics of airborne micro-organisms in a neurological intensive care
      unit: Results from China.
AB  - OBJECTIVE: To describe the characteristics of airborne micro-organisms in the
      environment in a Chinese neurological intensive care unit (NICU). METHODS: This
      prospective study monitored the air environment in two wards (large and small) of
      an NICU in a tertiary hospital in China for 12 months, using an LWC-1 centrifugal
      air sampler. Airborne micro-organisms were identified using standard microbiology
      techniques. RESULTS: The mean +/- SD number of airborne bacteria was
      significantly higher in the large ward than in the small ward (200 +/- 51 colony
      forming units [CFU]/m(3) versus 110 +/- 40 CFU/m(3), respectively). In the large
      ward only, the mean number of airborne bacteria in the autumn was significantly
      higher than in any of the other three seasons. A total of 279 airborne micro
      organisms were identified (large ward: 195; small ward: 84). There was no
      significant difference in the type and distribution of airborne micro-organisms
      between the large and small wards. The majority of airborne micro-organisms were
      Gram-positive cocci in both wards. CONCLUSION: These findings suggest that the
      number of airborne micro-organisms was related to the number of patients on the
      NICU ward.

PMID- 25762517
TI  - Leptin levels and lipoprotein profiles in patients with cholelithiasis.
AB  - OBJECTIVE: To determine the relationships between serum leptin and levels of
      lipoprotein(a) [Lp(a)], apolipoprotein A-1 (ApoA-1) and apolipoprotein B (ApoB)
      in patients with cholelithiasis. METHODS: Patients with ultrasound-confirmed
      cholelithiasis and controls frequency-matched for age, sex, body mass index,
      fasting blood glucose and haemoglobin A1c levels were recruited. Fasting blood
      samples from all study participants were assayed for glucose, haemoglobin A1c,
      total cholesterol, high density lipoprotein-cholesterol (HDL-C) and triglyceride.
      Serum Lp(a), ApoA-1 and ApoB levels were measured using nephelometric assays;
      serum leptin was measured using an enzyme-linked immunosorbent assay. RESULTS: A
      total of 90 patients with cholelithiasis and 50 controls were included in the
      study. Serum levels of leptin, Lp(a), total cholesterol, triglyceride and ApoB
      were significantly increased, and levels of ApoA-1 and HDL-C were significantly
      decreased, in patients with cholelithiasis compared with controls. Serum leptin
      in patients with cholelithiasis were significantly positively correlated with
      Lp(a) and ApoB and negatively correlated with ApoA-1. CONCLUSIONS: Patients with
      cholelithiasis have higher leptin levels and an altered lipoprotein profile
      compared with controls, with increased leptin levels being associated with
      increased Lp(a) and ApoB levels, and decreased ApoA-1 levels, in those with
      cholelithiasis.

PMID- 25762518
TI  - Comparison of multislice computed tomography and clinical scores for diagnosing
      acute appendicitis.
AB  - OBJECTIVE: To compare Raja Isteri Pengiran Anak Saleha Appendicitis (RIPASA) and
      Alvarado scores with multislice computed tomography (MSCT) for diagnosing acute
      appendicitis (AA). METHODS: This retrospective study included patients with
      abdominal pain who had undergone MSCT, and whose medical notes included RIPASA
      and Alvarado score parameters. MSCT was compared with RIPASA and Alvarado scores
      for diagnosing AA. RESULTS: Of 297 patients included, sensitivity, specificity
      and accuracy for diagnosing AA were 95.2%, 73.6% and 87.2% for RIPASA score
      (cutoff value 7.5) and 63.1%, 80.9% and 69.7% for Alvarado score (cutoff value
      7). Sensitivity, specificity and accuracy of MSCT for diagnosing AA were 98.9%,
      96.4% and 98.0%, respectively. In terms of accuracy, statistically significant
      differences were observed between RIPASA and Alvarado scores, and between MSCT
      and RIPASA scores. The mean RIPASA score was significantly different in the
      simple AA group (9.7 +/- 2.2) compared with other AA groups (10.5 +/- 1.7). No
      statistically significant difference was observed in RIPASA score between
      nonperforated and perforated AA. MSCT sensitivity, specificity and accuracy for
      diagnosing simple AA were 94.1%, 96.4% and 95.8%, respectively; for
      differentiating perforated and nonperforated AA, scores were 90.2%, 95.2% and
      94.1%, respectively. CONCLUSION: MSCT is the optimum diagnostic tool for AA,
      followed by RIPASA score and Alvarado score, particularly in diagnosing simple
      and perforated AA.

PMID- 25762519
TI  - Improved pruritus correlates with lower levels of IL-31 in CTCL patients under
      different therapeutic modalities.
AB  - Pruritus is one of the cardinal symptoms found in patients with leukemic
      cutaneous T cell lymphoma (CTCL). The nature of the pruritus experienced by CTCL
      patients is complex, involving different pathways and cell mediators, thus making
      it poorly responsive to conventional anti-itch therapies. Recent reports
      highlight the role of interleukin 31 (IL-31) as a novel cytokine involved in the
      pathogenesis of pruritus in atopic dermatitis and CTCL. Here we provide both in
      vivo and in vitro evidence suggesting that histone deacetylase (HDAC) inhibitors
      may mitigate itch through lowering of levels of IL-31-expressing T cells.
      Furthermore, we demonstrate that chemokine receptor type-4 (CCR4)-bearing T cells
      are a main source of IL-31 in CTCL, and that neutralizing the IL-31 pathway
      through targeting of the CCR4-expressing T cells may represent a promising
      therapeutic strategy for symptomatic relief in CTCL. 

PMID- 25762521
TI  - Mutation order affects cancer behavior.

PMID- 25762520
TI  - Successful newborn screening for SCID in the Navajo Nation.
AB  - Newborn screening (NBS) for severe combined immunodeficiency (SCID) identifies
      affected infants before the onset of life-threatening infections, permitting
      optimal treatment. Navajo Native Americans have a founder mutation in the DNA
      repair enzyme Artemis, resulting in frequent Artemis SCID (SCID-A). A pilot study
      at 2 Navajo hospitals assessed the feasibility of SCID NBS in this population.
      Dried blood spots from 1800 infants were assayed by PCR for T-cell receptor
      excision circles (TRECs), a biomarker for naive T cells. Starting in February
      2012, TREC testing transitioned to standard care throughout the Navajo Area
      Indian Health Service, and a total of 7900 infants were screened through July
      2014. One infant had low TRECs and was diagnosed with non-SCID T lymphopenia,
      while 4 had undetectable TRECs due to SCID-A, all of whom were referred for
      hematopoietic cell transplantation. This report establishes the incidence of SCID
      A and demonstrates effectiveness of TREC NBS in the Navajo.

PMID- 25762522
TI  - Quantifying the cellular uptake of semiconductor quantum dot nanoparticles by
      analytical electron microscopy.
AB  - Semiconductor quantum dot nanoparticles are in demand as optical biomarkers yet
      the cellular uptake process is not fully understood; quantification of numbers
      and the fate of internalized particles are still to be achieved. We have focussed
      on the characterization of cellular uptake of quantum dots using a combination of
      analytical electron microscopies because of the spatial resolution available to
      examine uptake at the nanoparticle level, using both imaging to locate particles
      and spectroscopy to confirm identity. In this study, commercially available
      quantum dots, CdSe/ZnS core/shell particles coated in peptides to target cellular
      uptake by endocytosis, have been investigated in terms of the agglomeration state
      in typical cell culture media, the traverse of particle agglomerates across U-2
      OS cell membranes during endocytosis, the merging of endosomal vesicles during
      incubation of cells and in the correlation of imaging flow cytometry and
      transmission electron microscopy to measure the final nanoparticle dose
      internalized by the U-2 OS cells. We show that a combination of analytical
      transmission electron microscopy and serial block face scanning electron
      microscopy can provide a comprehensive description of the internalization of an
      initial exposure dose of nanoparticles by an endocytically active cell population
      and how the internalized, membrane bound nanoparticle load is processed by the
      cells. We present a stochastic model of an endosome merging process and show that
      this provides a data-driven modelling framework for the prediction of cellular
      uptake of engineered nanoparticles in general. 

PMID- 25762523
TI  - Timing of Initiation of RRT and Modality Selection.
AB  - There is no shortage of studies and registry data examining outcomes of patients
      on dialysis and those with a renal transplant. However, recently, there has been
      a greater focus on the events leading up to the institution of kidney replacement
      therapy. Associative data suggest that early and consistent predialysis care
      leads to better outcomes, including greater take-on to home-based therapy,
      diminished use of tunneled venous hemodialysis catheters, and improved early and
      even late survival. What transpires during predialysis visits is also important.
      Simple dissemination of facts to the unprepared patient is unlikely to be
      effective in moving the patient and family along in the process of the series of
      choices that have to be made around therapy. A more flexible and circumspect
      approach is needed, including recognizing when the patient is or is not ready for
      change. There seems to be no optimal timing of dialysis start that can be applied
      to the ESRD population as a whole, although the pendulum seems to be swinging
      back toward symptom-based rather than eGFR-based starts. 

PMID- 25762524
TI  - Lactic Acidosis in a Patient with Type 2 Diabetes Mellitus.
AB  - Lactic acidosis occurs when lactate production exceeds its metabolism. There are
      many possible causes of lactic acidosis, and in any given patient, several causes
      may coexist. This Attending Rounds presents a case in point. Metformin's role in
      the pathogenesis of lactic acidosis in patients with diabetes mellitus is
      complex, as the present case illustrates. The treatment of lactic acidosis is
      controversial, except for the imperative to remedy its underlying cause. The use
      of sodium bicarbonate to treat the often alarming metabolic derangements may be
      quite efficacious in that regard but is of questionable benefit to patients.
      Renal replacement therapies (RRTs) have particular appeal in this setting for a
      variety of reasons, but their effect on clinical outcomes is untested. 

PMID- 25762525
TI  - The evolutionarily stable distribution of fitness effects.
AB  - The distribution of fitness effects (DFE) of new mutations is a key parameter in
      determining the course of evolution. This fact has motivated extensive efforts to
      measure the DFE or to predict it from first principles. However, just as the DFE
      determines the course of evolution, the evolutionary process itself constrains
      the DFE. Here, we analyze a simple model of genome evolution in a constant
      environment in which natural selection drives the population toward a dynamic
      steady state where beneficial and deleterious substitutions balance. The
      distribution of fitness effects at this steady state is stable under further
      evolution and provides a natural null expectation for the DFE in a population
      that has evolved in a constant environment for a long time. We calculate how the
      shape of the evolutionarily stable DFE depends on the underlying population
      genetic parameters. We show that, in the absence of epistasis, the ratio of
      beneficial to deleterious mutations of a given fitness effect obeys a simple
      relationship independent of population genetic details. Finally, we analyze how
      the stable DFE changes in the presence of a simple form of diminishing-returns
      epistasis.

PMID- 25762527
TI  - Reshaping faecal gut microbiota composition by the intake of trans-resveratrol
      and quercetin in high-fat sucrose diet-fed rats.
AB  - Diet-induced obesity is associated to an imbalance in the normal gut microbiota
      composition. Resveratrol and quercetin, widely known for their health beneficial
      properties, have low bioavailability, and when they reach the colon, they are
      targets of the gut microbial ecosystem. Hence, the use of these molecules in
      obesity might be considered as a potential strategy to modulate intestinal
      bacterial composition. The purpose of this study was to determine whether trans
      resveratrol and quercetin administration could counteract gut microbiota
      dysbiosis produced by high-fat sucrose diet (HFS) and, in turn, improve gut
      health. Wistar rats were randomised into four groups fed an HFS diet supplemented
      or not with trans-resveratrol [15 mg/kg body weight (BW)/day], quercetin (30
      mg/kg BW/day) or a combination of both polyphenols at those doses. Administration
      of both polyphenols together prevented body weight gain and reduced serum insulin
      levels. Moreover, individual supplementation of trans-resveratrol and quercetin
      effectively reduced serum insulin levels and insulin resistance. Quercetin
      supplementation generated a great impact on gut microbiota composition at
      different taxonomic levels, attenuating Firmicutes/Bacteroidetes ratio and
      inhibiting the growth of bacterial species previously associated to diet-induced
      obesity (Erysipelotrichaceae, Bacillus, Eubacterium cylindroides). Overall, the
      administration of quercetin was found to be effective in lessening HFS-diet
      induced gut microbiota dysbiosis. In contrast, trans-resveratrol supplementation
      alone or in combination with quercetin scarcely modified the profile of gut
      bacteria but acted at the intestinal level, altering the mRNA expression of tight
      junction proteins and inflammation-associated genes. 

PMID- 25762528
TI  - Performance of the new ACR/EULAR classification criteria for systemic sclerosis
      in clinical practice.
AB  - OBJECTIVE: The preliminary classification criteria for SSc lack sensitivity for
      mild/early SSc patients, therefore, the new ACR/EULAR classification criteria for
      SSc were developed. The objective of this study was to evaluate the performance
      of the new classification criteria for SSc in clinical practice in a cohort of
      mild/early patients. METHODS: Consecutive patients with a clinical diagnosis of
      SSc, based on expert opinion, were prospectively recruited and assessed according
      to the EULAR Scleroderma Trials and Research group (EUSTAR) and very early
      diagnosis of SSc (VEDOSS) recommendations. In some patients, missing values were
      retrieved retrospectively from the patient's records. Patients were grouped into
      established SSc (fulfilling the old ACR criteria) and mild/early SSc (not
      fulfilling the old ACR criteria). The new ACR/EULAR criteria were applied to all
      patients. RESULTS: Of the 304 patients available for the final analysis, 162/304
      (53.3%) had established SSc and 142/304 (46.7%) had mild/early SSc. All 162
      established SSc patients fulfilled the new ACR/EULAR classification criteria. The
      remaining 142 patients had mild/early SSc. Eighty of these 142 patients (56.3%)
      fulfilled the new ACR/EULAR classification criteria. Patients with mild/early SSc
      not fulfilling the new classification criteria were most often suffering from RP,
      had SSc-characteristic autoantibodies and had an SSc pattern on nailfold
      capillaroscopy. Taken together, the sensitivity of the new ACR/EULAR
      classification criteria for the overall cohort was 242/304 (79.6%) compared with
      162/304 (53.3%) for the ACR criteria. CONCLUSION: In this cohort with a focus on
      mild/early SSc, the new ACR/EULAR classification criteria showed higher
      sensitivity and classified more patients as definite SSc patients than the ACR
      criteria.

PMID- 25762529
TI  - US Supreme Court v Obamacare: round 2.

PMID- 25762526
TI  - Glucose induces sensitivity to oxygen deprivation and modulates insulin/IGF-1
      signaling and lipid biosynthesis in Caenorhabditis elegans.
AB  - Diet is a central environmental factor that contributes to the phenotype and
      physiology of individuals. At the root of many human health issues is the excess
      of calorie intake relative to calorie expenditure. For example, the increasing
      amount of dietary sugars in the human diet is contributing to the rise of obesity
      and type 2 diabetes. Individuals with obesity and type 2 diabetes have
      compromised oxygen delivery, and thus it is of interest to investigate the impact
      a high-sugar diet has on oxygen deprivation responses. By utilizing the
      Caenorhabditis elegans genetic model system, which is anoxia tolerant, we
      determined that a glucose-supplemented diet negatively impacts responses to
      anoxia and that the insulin-like signaling pathway, through fatty acid and
      ceramide synthesis, modulates anoxia survival. Additionally, a glucose
      supplemented diet alters lipid localization and initiates a positive chemotaxis
      response. Use of RNA-sequencing analysis to compare gene expression responses in
      animals fed either a standard or glucose-supplemented diet revealed that glucose
      impacts the expression of genes involved with multiple cellular processes
      including lipid and carbohydrate metabolism, stress responses, cell division, and
      extracellular functions. Several of the genes we identified show homology to
      human genes that are differentially regulated in response to obesity or type 2
      diabetes, suggesting that there may be conserved gene expression responses
      between C. elegans fed a glucose-supplemented diet and a diabetic and/or obesity
      state observed in humans. These findings support the utility of the C. elegans
      model for understanding the molecular mechanisms regulating dietary-induced
      metabolic diseases.

PMID- 25762530
TI  - Prevention of chemically induced urinary bladder cancers by naproxen: protocols
      to reduce gastric toxicity in humans do not alter preventive efficacy.
AB  - The COX inhibitors (NSAID/Coxibs) are a major focus for the chemoprevention of
      cancer. The COX-2-specific inhibitors have progressed to clinical trials and have
      shown preventive efficacy in colon and skin cancers. However, they have
      significant adverse cardiovascular effects. Certain NSAIDs (e.g., naproxen) have
      a good cardiac profile, but can cause gastric toxicity. The present study
      examined protocols to reduce this toxicity of naproxen. Female Fischer-344 rats
      were treated weekly with the urinary bladder-specific carcinogen
      hydroxybutyl(butyl)nitrosamine (OH-BBN) for 8 weeks. Rats were dosed daily with
      NPX (40 mg/kg body weight/day, gavage) or with the proton pump inhibitor
      omeprazole (4.0 mg/kg body weight/day) either singly or in combination beginning
      2 weeks after the final OH-BBN. OH-BBN-treated rats, 96% developed urinary
      bladder cancers. While omeprazole alone was ineffective (97% cancers), naproxen
      alone or combined with omeprazole-prevented cancers, yielding 27 and 35% cancers,
      respectively. In a separate study, OH-BBN -: treated rats were administered
      naproxen: (A) daily, (B) 1 week daily naproxen/1week vehicle, (C) 3 weeks daily
      naproxen/3 week vehicle, or (D) daily vehicle beginning 2 weeks after last OH-BBN
      treatment. In the intermittent dosing study, protocol A, B, C, and D resulted in
      palpable cancers in 27%, 22%, 19%, and 96% of rats (P < 0.01). Short-term
      naproxen treatment increased apoptosis, but did not alter proliferation in the
      urinary bladder cancers. Two different protocols that should decrease the gastric
      toxicity of NSAIDs in humans did not alter chemopreventive efficacy. This should
      encourage the use of NSAIDs (e.g., naproxen) in clinical prevention trials.

PMID- 25762532
TI  - Stress in parents of children born very preterm is predicted by child
      externalising behaviour and parent coping at age 7 years.
AB  - OBJECTIVE: To examine factors which predict parenting stress in a longitudinal
      cohort of children born very preterm, and seen at age 7 years. METHODS: We
      recruited 100 very preterm (<=32 weeks gestational age) child-parent dyads and a
      control group of 50 term-born dyads born between 2001 and 2004 with follow-up at
      7 years. Parents completed the Parenting Stress Index, Ways of Coping
      Questionnaire, Child Behavior Check List, Beck Depression Inventory and the State
      Trait Anxiety Inventory questionnaires. Child IQ was assessed using the Wechsler
      Intelligence Scale-IV. RESULTS: After controlling for maternal education, parents
      of preterm children (95% CI 111.1 to 121.4) scored higher (p=0.027) on the
      Parenting Stress Index than term-born controls (95% CI 97.8 to 113.2). Regression
      analyses showed that child externalising behaviour, sex and parent
      escape/avoidance coping style, predicted higher parenting stress in the preterm
      group. Parents of preterm girls expressed higher levels of stress than those of
      boys. CONCLUSIONS: Maladaptive coping strategies contribute to greater stress in
      parents of very preterm children. Our findings suggest that these parents need
      support for many years after birth of a very preterm infant.

PMID- 25762533
TI  - Do small doses of atropine (<0.1 mg) cause bradycardia in young children?
AB  - OBJECTIVE: To determine the heart rate response to atropine (<0.1 mg) in
      anaesthetised young infants. DESIGN: Prospective, observational and controlled.
      SETTING: Elective surgery. PATIENTS: Sixty unpremedicated healthy infants less
      than 15 kg were enrolled. Standard monitoring was applied. Anaesthesia was
      induced by mask with nitrous oxide (66%) and oxygen (33%) followed by sevoflurane
      (8%). INTERVENTIONS: Intravenous (IV) atropine (5 ug/kg) was flushed into a fast
      flowing IV. The ECG was recorded continuously from 30 s before the atropine until
      5 min afterwards. MAIN OUTCOME MEASURES: The incidence of bradycardia and
      arrhythmias was determined from the ECGs by a blinded observer. RESULTS: The
      median (IQR) age was 6.5 (4-12) months and the mean (95% CI) weight was 8.6 (8.1
      to 9.1) kg. The mean (95% CI) dose of atropine was 40.9 (37.3 to 44) ug.
      Bradycardia did not occur. Two infants developed premature atrial contractions
      and one developed a premature ventricular contraction. When compared with
      baseline values, heart rate increased by 7% 30 s after atropine, 14% 1 min after
      atropine and 25% 5 min after atropine. Twenty-nine infants (48%) experienced
      tachycardia (>20% above baseline rate) after atropine lasting 222.7 s (range 27.9
      286). The change in heart rate 5 min after atropine was inversely related to the
      baseline heart rate. CONCLUSIONS: The upper 95% CI for the occurrence of
      bradycardia in the entire population of infants based on a zero incidence in this
      study is 5%. These results rebut the notion that atropine <0.1 mg IV causes
      bradycardia in young infants. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov
      #NCT01819064.

PMID- 25762534
TI  - Bilateral dislocation of the ocular lens in an African child.

PMID- 25762531
TI  - Laboratory and clinical aspects of human herpesvirus 6 infections.
AB  - Human herpesvirus 6 (HHV-6) is a widespread betaherpesvirus which is genetically
      related to human cytomegalovirus (HCMV) and now encompasses two different
      species: HHV-6A and HHV-6B. HHV-6 exhibits a wide cell tropism in vivo and, like
      other herpesviruses, induces a lifelong latent infection in humans. As a
      noticeable difference with respect to other human herpesviruses, genomic HHV-6
      DNA is covalently integrated into the subtelomeric region of cell chromosomes
      (ciHHV-6) in about 1% of the general population. Although it is infrequent, this
      may be a confounding factor for the diagnosis of active viral infection. The
      diagnosis of HHV-6 infection is performed by both serologic and direct methods.
      The most prominent technique is the quantification of viral DNA in blood, other
      body fluids, and organs by means of real-time PCR. Many active HHV-6 infections,
      corresponding to primary infections, reactivations, or exogenous reinfections,
      are asymptomatic. However, the virus may be the cause of serious diseases,
      particularly in immunocompromised individuals. As emblematic examples of HHV-6
      pathogenicity, exanthema subitum, a benign disease of infancy, is associated with
      primary infection, whereas further virus reactivations can induce severe
      encephalitis cases, particularly in hematopoietic stem cell transplant
      recipients. Generally speaking, the formal demonstration of the causative role of
      HHV-6 in many acute and chronic human diseases is difficult due to the ubiquitous
      nature of the virus, chronicity of infection, existence of two distinct species,
      and limitations of current investigational tools. The antiviral compounds
      ganciclovir, foscarnet, and cidofovir are effective against active HHV-6
      infections, but the indications for treatment, as well as the conditions of drug
      administration, are not formally approved to date. There are still numerous
      pending questions about HHV-6 which should stimulate future research works on the
      pathophysiology, diagnosis, and therapy of this remarkable human virus. 

PMID- 25762537
TI  - Sleep and Attention in Children With ADHD and Typically Developing Peers.
AB  - OBJECTIVE: The objective of this study was to examine the relationships between
      sleep and attention in both typically developing (TD) children and children with
      ADHD. METHOD: The current study examined sleep and attention in 50 children, from
      6 to 12 years of age (25 ADHD, 25 TD). Attention was measured using the Conners'
      Parent Rating Scale-Revised: Long Version and the Attention Network Test
      Interaction (ANT-I), which provided an objective measure of alerting, orienting,
      and executive attention. Sleep was objectively measured using actigraphy.
      RESULTS: Children with ADHD had poorer alerting and executive attention on the
      ANT-I, as well as poorer parent-reported attention. In addition, poor sleep
      predicted performance on alerting attention for children with ADHD and TD
      children, whereas the interaction between poor sleep and ADHD diagnosis predicted
      executive attention scores. CONCLUSION: The findings of the current study
      highlight the importance of ensuring children are getting good quality sleep to
      optimize attention, particularly for children with ADHD.

PMID- 25762538
TI  - Use of Polynomial Regression to Investigate Biased Self-Perceptions and ADHD
      Symptoms in Young Adolescents.
AB  - OBJECTIVE: This study investigated biased self-perceptions of academic and social
      competence among young adolescents with a range of ADHD symptoms. The goal was to
      better understand how to measure agreement and disagreement between competence
      ratings from multiple informants. METHOD: The commonly used discrepancy
      methodology was used along with polynomial regression/response surface analyses
      to explore the relationship between biased self-perceptions and ADHD symptoms.
      Participants were 164 middle school students and their homeroom teachers.
      Students and teachers completed measures about academic and social competence,
      and teachers rated ADHD symptoms. RESULTS: Discrepancy score and polynomial
      regression/response surface analyses both supported the relationship between
      student overestimation of competence and ADHD symptoms. Response surface analyses
      also suggest that some students with ADHD symptoms accurately perceive their
      impairments, particularly in the academic domain. CONCLUSION: Findings
      demonstrate the importance of using more advanced methods to understand the
      relationship between both accurate and discrepant perceptions of competence and
      ADHD symptoms.

PMID- 25762536
TI  - Spliceosome assembly in the absence of stable U4/U6 RNA pairing.
AB  - The cycle of spliceosome assembly, intron excision, and spliceosome disassembly
      involves large-scale structural rearrangements of U6 snRNA that are functionally
      important. U6 enters the splicing pathway bound to the Prp24 protein, which
      chaperones annealing of U6 to U4 RNA to form a U4/U6 di-snRNP. During catalytic
      activation of the assembled spliceosome, U4 snRNP is released and U6 is paired to
      U2 snRNA. Here we show that point mutations in U4 and U6 that decrease U4/U6 base
      pairing in vivo are lethal in combination. However, this synthetic phenotype is
      rescued by a mutation in U6 that alters a U6-Prp24 contact and stabilizes U2/U6.
      Remarkably, the resulting viable triple mutant strain lacks detectable U4/U6 base
      pairing and U4/U6 di-snRNP. Instead, this strain accumulates free U4 snRNP,
      protein-free U6 RNA, and a novel complex containing U2/U6 di-snRNP. Further
      mutational analysis indicates that disruption of the U6-Prp24 interaction rather
      than stabilization of U2/U6 renders stable U4/U6 di-snRNP assembly nonessential.
      We propose that an essential function of U4/U6 pairing is to displace Prp24 from
      U6 RNA, and thus a destabilized U6-Prp24 complex renders stable U4/U6 pairing
      nonessential. 

PMID- 25762539
TI  - European Commission's proposals on trade secrets.

PMID- 25762540
TI  - Antitumor immunity triggered by melphalan is potentiated by melanoma cell surface
      associated calreticulin.
AB  - Systemic chemotherapy generally has been considered immunosuppressive, but it has
      become evident that certain chemotherapeutic drugs elicit immunogenic danger
      signals in dying cancer cells that can incite protective antitumor immunity. In
      this study, we investigated whether locoregionally applied therapies, such as
      melphalan, used in limb perfusion for melanoma (Mel-ILP) produce related
      immunogenic effects. In human melanoma biopsies, Mel-ILP treatment upregulated
      IL1B, IL8, and IL6 associated with their release in patients' locoregional sera.
      Although induction of apoptosis in melanoma cells by melphalan in vitro did not
      elicit threshold levels of endoplasmic reticulum and reactive oxygen species
      stress associated with danger signals, such as induction of cell-surface
      calreticulin, prophylactic immunization and T-cell depletion experiments showed
      that melphalan administration in vivo could stimulate a CD8(+) T cell-dependent
      protective antitumor response. Interestingly, the vaccination effect was
      potentiated in combination with exogenous calreticulin, but not tumor necrosis
      factor, a cytokine often combined with Mel-ILP. Our results illustrate how
      melphalan triggers inflammatory cell death that can be leveraged by
      immunomodulators such as the danger signal calreticulin.

PMID- 25762542
TI  - Promoting health and equity: a theme that is more relevant than ever.

PMID- 25762541
TI  - The 2014 Bernard B. Brodie award lecture-epoxide hydrolases: drug metabolism to
      therapeutics for chronic pain.
AB  - Dr. Bernard Brodie's legacy is built on fundamental discoveries in pharmacology
      and drug metabolism that were then translated to the clinic to improve patient
      care. Similarly, the development of a novel class of therapeutics termed the
      soluble epoxide hydrolase (sEH) inhibitors was originally spurred by fundamental
      research exploring the biochemistry and physiology of the sEH. Here, we present
      an overview of the history and current state of research on epoxide hydrolases,
      specifically focusing on sEHs. In doing so, we start with the translational
      project studying the metabolism of the insect juvenile hormone mimic R-20458 [(E)
      6,7-epoxy-1-(4-ethylphenoxy)-3,7-dimethyl-2-octene], which led to the
      identification of the mammalian sEH. Further investigation of this enzyme and its
      substrates, including the epoxyeicosatrienoic acids, led to insight into
      mechanisms of inflammation, chronic and neuropathic pain, angiogenesis, and other
      physiologic processes. This basic knowledge in turn led to the development of
      potent inhibitors of the sEH that are promising therapeutics for pain,
      hypertension, chronic obstructive pulmonary disorder, arthritis, and other
      disorders. 

PMID- 25762543
TI  - Marrying research evidence and policies in Latin America and the Caribbean: the
      case of violence.

PMID- 25762551
TI  - Origin and domestication of papaya Yh chromosome.
AB  - Sex in papaya is controlled by a pair of nascent sex chromosomes. Females are XX,
      and two slightly different Y chromosomes distinguish males (XY) and
      hermaphrodites (XY(h)). The hermaphrodite-specific region of the Y(h) chromosome
      (HSY) and its X chromosome counterpart were sequenced and analyzed previously. We
      now report the sequence of the entire male-specific region of the Y (MSY). We
      used a BAC-by-BAC approach to sequence the MSY and resequence the Y regions of 24
      wild males and the Y(h) regions of 12 cultivated hermaphrodites. The MSY and HSY
      regions have highly similar gene content and structure, and only 0.4% sequence
      divergence. The MSY sequences from wild males include three distinct haplotypes,
      associated with the populations' geographic locations, but gene flow is detected
      for other genomic regions. The Y(h) sequence is highly similar to one Y haplotype
      (MSY3) found only in wild dioecious populations from the north Pacific region of
      Costa Rica. The low MSY3-Y(h) divergence supports the hypothesis that
      hermaphrodite papaya is a product of human domestication. We estimate that Y(h)
      arose only ~ 4000 yr ago, well after crop plant domestication in Mesoamerica
      >6200 yr ago but coinciding with the rise of the Maya civilization. The Y(h)
      chromosome has lower nucleotide diversity than the Y, or the genome regions that
      are not fully sex-linked, consistent with a domestication bottleneck. The
      identification of the ancestral MSY3 haplotype will expedite investigation of the
      mutation leading to the domestication of the hermaphrodite Y(h) chromosome. In
      turn, this mutation should identify the gene that was affected by the carpel
      suppressing mutation that was involved in the evolution of males.

PMID- 25762552
TI  - Effect of minichromosome maintenance protein 2 deficiency on the locations of DNA
      replication origins.
AB  - Minichromosome maintenance (MCM) proteins are loaded onto chromatin during G1
      phase and define potential locations of DNA replication initiation. MCM protein
      deficiency results in genome instability and high rates of cancer in mouse
      models. Here we develop a method of nascent strand capture and release and show
      that MCM2 deficiency reduces DNA replication initiation in gene-rich regions of
      the genome. DNA structural properties are shown to correlate with sequence motifs
      associated with replication origins and with locations that are preferentially
      affected by MCM2 deficiency. Reduced nascent strand density correlates with sites
      of recurrent focal CNVs in tumors arising in MCM2-deficient mice, consistent with
      a direct relationship between sites of reduced DNA replication initiation and
      genetic damage. Between 10% and 90% of human tumors, depending on type, carry
      heterozygous loss or mutation of one or more MCM2-7 genes, which is expected to
      compromise DNA replication origin licensing and result in elevated rates of
      genome damage at a subset of gene-rich locations. 

PMID- 25762554
TI  - Letter from the Editorial Board: Aims of Briefings in Bioinformatics further
      defined.

PMID- 25762553
TI  - Unraveling determinants of transcription factor binding outside the core binding
      site.
AB  - Binding of transcription factors (TFs) to regulatory sequences is a pivotal step
      in the control of gene expression. Despite many advances in the characterization
      of sequence motifs recognized by TFs, our ability to quantitatively predict TF
      binding to different regulatory sequences is still limited. Here, we present a
      novel experimental assay termed BunDLE-seq that provides quantitative
      measurements of TF binding to thousands of fully designed sequences of 200 bp in
      length within a single experiment. Applying this binding assay to two yeast TFs,
      we demonstrate that sequences outside the core TF binding site profoundly affect
      TF binding. We show that TF-specific models based on the sequence or DNA shape of
      the regions flanking the core binding site are highly predictive of the measured
      differential TF binding. We further characterize the dependence of TF binding,
      accounting for measurements of single and co-occurring binding events, on the
      number and location of binding sites and on the TF concentration. Finally, by
      coupling our in vitro TF binding measurements, and another application of our
      method probing nucleosome formation, to in vivo expression measurements carried
      out with the same template sequences serving as promoters, we offer insights into
      mechanisms that may determine the different expression outcomes observed. Our
      assay thus paves the way to a more comprehensive understanding of TF binding to
      regulatory sequences and allows the characterization of TF binding determinants
      within and outside of core binding sites. 

PMID- 25762555
TI  - Letter to the editor: On reviews and papers on new methods.

PMID- 25762556
TI  - An isolated left ventricular septal aneurysm in Behcet's disease.

PMID- 25762557
TI  - Superior vena cava syndrome associated with a right-to-left extracardiac shunt.

PMID- 25762558
TI  - Myocardial mechanical and QTc dispersion for the detection of significant
      coronary artery disease.
AB  - AIMS: Ischaemic but viable myocardium may exhibit prolongation of contraction and
      QT interval duration, but it is largely unknown whether non-invasive assessment
      of regional heterogeneities of myocardial deformation and QT interval duration
      could identify patients with significant coronary artery disease (CAD). METHODS
      AND RESULTS: We retrospectively studied 205 patients with suspected CAD who
      underwent coronary angiography. QTc dispersion was assessed from a 12-lead
      electrocardiogram (ECG) as the difference between the longest and shortest QTc
      intervals. Contraction duration was assessed as time from the ECG R-(Q-)wave to
      peak longitudinal strain in each of 18 left ventricular segments. Mechanical
      dispersion was defined as either the standard deviation of 18 time intervals
      (dispersionSD18) or as the difference between the longest and shortest time
      intervals (dispersiondelta). Longitudinal strain was measured by speckle tracking
      echocardiography. Mean contraction duration was longer in patients with
      significant CAD compared with control subjects (428 +/- 51 vs. 410 +/- 40 ms; P =
      0.032), and it was correlated to QTc interval duration (r = 0.47; P < 0.001). In
      contrast to QTc interval duration and dispersion, both parameters of mechanical
      dispersion were independently associated with CAD (P < 0.001) and had incremental
      value over traditional risk factors, wall motion abnormalities, and global
      longitudinal strain (GLS) for the detection of significant CAD. CONCLUSION: The
      QTc interval and myocardial contraction duration are related to the presence of
      significant CAD in patients without a history of previous myocardial infarction.
      Myocardial mechanical dispersion has an incremental value to GLS for identifying
      patients with significant CAD.

PMID- 25762559
TI  - Association between tissue characteristics assessed with optical coherence
      tomography and mid-term results after percutaneous coronary intervention for in
      stent restenosis lesions: a comparison between balloon angioplasty, paclitaxel
      coated balloon dilatation, and drug-eluting stent implantation.
AB  - AIMS: Morphological assessment of neointimal tissue using optical coherence
      tomography (OCT) is important for clarifying the pathophysiology of in-stent
      restenosis (ISR) lesions. The aim of this study was to determine the impact of
      OCT findings on recurrence of ISR after various types of percutaneous coronary
      intervention (PCI) including plain old balloon angioplasty (POBA), paclitaxel
      coated balloon (PCB) dilatation, and drug-eluting stent (DES) implantation.
      METHODS AND RESULTS: Between June 2008 and August 2013, we performed PCI for 428
      ISR lesions in 379 patients using POBA (78 lesions, POBA group), PCB dilatation
      (202 lesions, PCB group), and DES implantation (148 lesions, DES group).
      Morphological assessment of neointimal tissue at the minimum lumen area site to
      determine restenotic tissue structure (homogeneous, heterogeneous, or layered
      type) using OCT was performed. We examined the association between tissue
      structure and midterm results including ISR and target lesion revascularization
      (TLR) rates. The patients were 308 men and 71 women with a mean age of 68.9 +/-
      9.4 years. The mean follow-up period was 211 +/- 40 days. ISR and TLR rates of
      lesions with a homogeneous structure were significantly higher in the POBA group
      than in the PCB group (ISR: 54.8 vs. 19.1%, P < 0.001; TLR: 38.7 vs. 10.6%, P <
      0.001) and DES group (ISR: 54.8 vs. 19.6%, P = 0.002; TLR: 38.7 vs. 10.7%, P =
      0.005), whereas there were no differences in ISR and TLR rates between the three
      groups in lesions with a heterogeneous structure. CONCLUSION: Morphological
      assessment of ISR tissue using OCT might suggest favourable types of PCI for ISR
      lesions.

PMID- 25762560
TI  - The influence of frame rate on two-dimensional speckle-tracking strain
      measurements: a study on silico-simulated models and images recorded in patients.
AB  - AIMS: Ultrasound-derived myocardial strain can render valuable diagnostic and
      prognostic information. However, acquisition settings can have an important
      impact on the measurements. Frame rate (i.e. temporal resolution) seems to be of
      particular importance. The aim of this study was to find the optimal range of
      frame rates needed for most accurate and reproducible 2D strain measurements
      using a 2D speckle-tracking software package. METHODS AND RESULTS: Synthetic two
      dimensional (2D) ultrasound grey-scale images of the left ventricle (LV) were
      generated in which the strain in longitudinal, circumferential, and radial
      direction were precisely known from the underlying kinematic LV model. Four
      different models were generated at frame rates between 20 and 110 Hz. The
      resulting images were repeatedly analysed. Results of the synthetic data were
      validated in 66 patients, where long- and short-axis recordings at different
      frame rates were analysed. In simulated data, accurate strain estimates could be
      achieved at >30 frames per cycle (FpC) for longitudinal and circumferential
      strains. Lower FpC underestimated strain systematically. Radial strain estimates
      were less accurate and less reproducible. Patient strain displayed the same
      plateaus as in the synthetic models. Higher noise and the presence of artefacts
      in patient data were followed by higher measurement variability. CONCLUSION:
      Standard machine settings with a FR of 50-60 Hz allow correct assessment of peak
      global longitudinal and circumferential strain. Correct definition of the region
      of interest within the myocardium as well as the reduction of noise and artefacts
      seem to be of highest importance for accurate 2D strain estimation.

PMID- 25762561
TI  - Value of anatomical aortic valve area using real-time three-dimensional
      transoesophageal echocardiography in patients with aortic stenosis: a comparison
      between tricuspid and bicuspid aortic valves.
AB  - AIMS: Accurate assessment of disease severity is critical for appropriate
      treatment of patients with aortic stenosis (AS). This study investigated the
      influence of aortic-valve morphology on the determination of anatomical aortic
      valve area (AVA) in patients with AS. METHODS AND RESULTS: This prospective study
      included 126 patients with AS who underwent transoesophageal echocardiography
      (TEE). Aortic-valve area was measured using (i) planimetric two-dimensional (2D)
      TEE, (ii) volumetric three-dimensional (3D) TEE, and (iii) the continuity
      equation (CE) obtained with transthoracic echocardiography. Of these, 20 patients
      also underwent contrast-enhanced multidetector computed tomography (MDCT). Aortic
      valve area was measured from multiplanar reconstruction of the MDCT images. Of
      the 126 patients, 20 (15.9%) were diagnosed with bicuspid AS and 106 were
      diagnosed with tricuspid AS. There was an excellent correlation between AVAADCT
      and AVA3DTEE (r = 0.83, P < 0.001) and a somewhat lower correlation between
      AVAADCT and AVA2DTEE (r = 0.63, P = 0.006). In the tricuspid AS group, both
      AVA2DTEE and AVA3DTEE significantly correlated with AVACE (r = 0.63, mean
      difference 0.13 +/- 0.24 cm(2), and r = 0.83, mean difference 0.03 +/- 0.12
      cm(2), respectively, both P < 0.001). In contrast, in the bicuspid AS group,
      AVA3DTEE significantly correlated with AVACE (r = 0.83, mean difference 0.10 +/-
      0.18 cm(2), P < 0.001), whereas AVA2DTEE did not (r = 0.42, mean difference 0.48
      +/- 0.32 cm(2), P = 0.066). CONCLUSION: Aortic-valve morphology influenced the
      assessment of anatomical AVA in patients with AS, and 3D TEE is useful for
      assessing anatomical AVA regardless of aortic-valve morphology.

PMID- 25762562
TI  - Energy loss in the left ventricle obtained by vector flow mapping as a new
      quantitative measure of severity of aortic regurgitation: a combined experimental
      and clinical study.
AB  - AIMS: In aortic regurgitation (AR), energy loss (EL) produced by inefficient
      turbulent flow may be a burden to the heart predicting decompensation. We
      attempted to quantify EL in AR induced in an acute dog model and in patients with
      chronic AR using novel echocardiographic method vector flow mapping (VFM).
      METHODS AND RESULTS: In 11 anaesthetized open-chest dogs, AR was induced by
      distorting the aortic valve with a pigtail catheter, in totally 20 cases.
      Regurgitant fraction was determined using pulsed Doppler echocardiography, <30%
      considered mild to moderate (Group 1, n = 11) and >=30% moderate to severe (Group
      2, n = 9). The clinical study consisted of 22 patients with various degrees of
      AR; 11 mild to moderate (Group 1) and 11 moderate to severe (Group 2), and
      compared with 12 normals. VFM is based on continuity equation applied to colour
      Doppler and speckle tracking velocities, acquired from apical long-axis image. EL
      was calculated frame by frame, averaged from three beats. In the dog study,
      diastolic EL increased significantly with severity of AR (baseline vs. Group 1
      vs. Group 2: 3.8 +/- 1.6 vs. 13.0 +/- 5.0 vs. 22.4 +/- 14.0 [J/(m s)], ANOVA P =
      0.0001). Similar to dogs, diastolic EL also increased in humans by the severity
      of AR (control vs. Group 1 vs. Group 2: 2.8 +/- 1.5 vs. 14.3 +/- 11.5 vs. 18.6 +/
      2.3 [J/(m s)], ANOVA P = 0.001). CONCLUSION: VFM provides a promising method to
      quantify diastolic EL in AR. Diastolic EL increases in AR proportional to its
      severity. EL may be useful to determine the severity of disease from the aspect
      of cardiac load.

PMID- 25762563
TI  - Combining FDG-PET and 99mTc-SPECT to predict functional outcome after coronary
      artery bypass surgery.
AB  - AIMS: Single-photon emission computed tomography (SPECT) and positron emission
      tomography (PET) are suggested to improve clinical decision-making in ischaemic
      cardiomyopathy. Here, we present a unique cohort of patients who underwent
      nuclear medicine studies and cardiac magnetic resonance imaging (MRI) both before
      and 1 year after coronary artery bypass (CABG) surgery to assess benefit from
      surgery. METHODS AND RESULTS: Before CABG, we applied three quantitative
      techniques using (18)F-fluorodeoxyglucose-PET and (99m)technetium-tetrofosmin
      SPECT with a software tool to measure defects with hypoperfused but viable and
      non-viable myocardium in 15 patients. One method used solely PET, two others
      combined PET and SPECT at different thresholds. As a reference, we used change in
      left-ventricular (LV) function and volume by MRI. Preoperatively, ischaemic but
      viable areas detected by the method with a 10% threshold combining PET-SPECT and
      the PET-only method correlated significantly with preoperative regional wall
      thickening (WT; P = 0.03 and P = 0.005, respectively). When compared with global
      functional outcome (change in LV ejection fraction) and LV remodelling (change in
      end-diastolic volume) 1 year postoperatively, no correlation appeared with
      preoperative PET- or PET-SPECT-derived viable or non-viable tissue. Neither was
      any correlation observable between local change in WT and local preoperative
      defect size evaluated by any of these three methods. CONCLUSION: Preoperatively,
      PET and PET-SPECT with 10% threshold detected dysfunctional myocardium, but all
      analysis methods failed to predict 1-year functional outcome assessed by MRI. In
      patients with three-vessel disease and heart failure, SPECT perfusion and PET
      viability study results show substantial heterogeneity; this should be considered
      when selecting patients for revascularization.

PMID- 25762564
TI  - Low-dose CT coronary angiography with a novel IntraCycle motion-correction
      algorithm in patients with high heart rate or heart rate variability.
AB  - AIMS: Motion artefacts due to high or irregular heart rate (HR) are common
      limitations of coronary computed tomography (CT) angiography (CCTA). The aim of
      the study was to evaluate the impact of a new motion-correction (MC) algorithm
      used in conjunction with low-dose prospective ECG-triggering CCTA on motion
      artefacts, image quality, and coronary assessability. METHODS AND RESULTS: Among
      380 patients undergoing CCTA for suspected CAD, we selected 120 patients with pre
      scanning HR >70 bpm or HR variability (HRv) >10 bpm during scanning irrespective
      of pre-scanning HR or both conditions. In patients with pre-scanning HR <65 or
      >=65 bpm, prospective ECG triggering with padding of 80 ms (58 cases) or padding
      of 200 ms (62 cases) was used, respectively. Mean pre-scanning HR and HRv were 70
      +/- 7 and 10.9 +/- 4 bpm, respectively. Overall, the mean effective dose was 3.4
      +/- 1.3 mSv, while a lower dose (2.4 +/- 0.9 mSv) was measured for padding of 80
      ms. In a segment-based analysis, coronary assessability was significantly higher
      (P < 0.0001) with MC (97%) when compared with standard (STD) reconstruction (81%)
      due to a significant reduction (P < 0.0001) in severe artefacts (54 vs. 356
      cases, respectively). An artefact sub-analysis showed significantly lower number
      of motion artefacts and artefacts related to chest movement with MC (16 and 4
      cases) than with STD reconstruction (286 and 24 cases, P < 0.0001 and P < 0.05,
      respectively). The number of coronary segments ranked among those of excellent
      image quality was significantly higher with MC (P < 0.001). CONCLUSIONS: The MC
      algorithm improves CCTA image quality and coronary assessability in patients with
      high HR and HRv, despite low radiation dose.

PMID- 25762565
TI  - Solid waste management scenarios for Cetinje in Montenegro.
AB  - This study presents the options for source-segregation and selective collection
      of recyclable waste fractions for Cetinje, Montenegro, with the aim of meeting
      the European Union 50% waste recycling target in 2023, and extending collection
      and disposal system that builds on the existing strengths of the city. To this
      end, three options were considered: (1) source separation and separate collection
      of dry recyclable materials and central sorting of residual waste; (2) source
      separation and collection of co-mingled dry recyclable materials, and central
      sorting in a clean material recovery facility of comingled recyclables and
      central sorting of residual waste; (3) collection of mixed waste (current
      situation) and subsequent central sorting. Scenarios 1 and 2 were found to meet
      the European Union 50% recycling target in 2023, provided that a fast
      implementation of the new separate collection schemes to fine sort the co-mingled
      collected recyclable materials is available. Finally, a financial evaluation was
      made for the options and the investment and operational costs over a 20-year
      period were estimated. Unit costs for Scenario 3 were found to be lower than for
      Scenario 1 and 2. As Scenario 3 will not meet the future European Union recycling
      targets, Scenario 2 has been pointed as the most feasible scenario for Cetinje,
      with reference to the expected lower total costs compared with Scenario 1. 

PMID- 25762566
TI  - Sustainability and shared smart and mutual--green growth (SSaM-GG) in Korean
      medical waste management.
AB  - Since medical insurance was introduced in the Republic of Korea, there have been
      several increases concerning medical waste. In order to solve these problems, we
      have applied life cycle assessment and life cycle cost. But these methods cannot
      be a perfect decision-making tool because they can only evaluate environmental
      and economic burdens. Thus, as one of many practical methods the shared smart and
      mutual - green growth considers economic growth, environmental protection, social
      justice, science technology and art, and mutual voluntarism when applied to
      medical waste management in the Republic of Korea. Four systems were considered:
      incineration, incineration with heat recovery, steam sterilisation, and microwave
      disinfection. This research study aimed to assess pollutant emissions from
      treatment, transport, and disposal. Global warming potential, photochemical
      oxidant creation potential, acidifications potential, and human toxicity are
      considered to be environmental impacts. Total investment cost, transport cost,
      operation, and maintenance cost for the medical waste are considered in the
      economy evaluations though life cycle cost. The social development, science
      technology and art, and mutual voluntarism are analysed through the Delphi-method
      conducted by expert groups related to medical waste. The result is that
      incineration with heat recovery is the best solution. However, when heat recovery
      is impossible, incineration without heat recovery becomes the next best choice.
      That is why 95% of medical waste is currently treated by both incineration and
      incineration with heat recovery within the Republic of Korea. 

PMID- 25762567
TI  - Drug-disease and drug-drug interactions: systematic examination of
      recommendations in 12 UK national clinical guidelines.
AB  - OBJECTIVE: To identify the number of drug-disease and drug-drug interactions for
      exemplar index conditions within National Institute of Health and Care Excellence
      (NICE) clinical guidelines. DESIGN: Systematic identification, quantification,
      and classification of potentially serious drug-disease and drug-drug interactions
      for drugs recommended by NICE clinical guidelines for type 2 diabetes, heart
      failure, and depression in relation to 11 other common conditions and drugs
      recommended by NICE guidelines for those conditions. SETTING: NICE clinical
      guidelines for type 2 diabetes, heart failure, and depression MAIN OUTCOME
      MEASURES: Potentially serious drug-disease and drug-drug interactions. RESULTS:
      Following recommendations for prescription in 12 national clinical guidelines
      would result in several potentially serious drug interactions. There were 32
      potentially serious drug-disease interactions between drugs recommended in the
      guideline for type 2 diabetes and the 11 other conditions compared with six for
      drugs recommended in the guideline for depression and 10 for drugs recommended in
      the guideline for heart failure. Of these drug-disease interactions, 27 (84%) in
      the type 2 diabetes guideline and all of those in the two other guidelines were
      between the recommended drug and chronic kidney disease. More potentially serious
      drug-drug interactions were identified between drugs recommended by guidelines
      for each of the three index conditions and drugs recommended by the guidelines
      for the 11 other conditions: 133 drug-drug interactions for drugs recommended in
      the type 2 diabetes guideline, 89 for depression, and 111 for heart failure. Few
      of these drug-disease or drug-drug interactions were highlighted in the
      guidelines for the three index conditions. CONCLUSIONS: Drug-disease interactions
      were relatively uncommon with the exception of interactions when a patient also
      has chronic kidney disease. Guideline developers could consider a more systematic
      approach regarding the potential for drug-disease interactions, based on
      epidemiological knowledge of the comorbidities of people with the disease the
      guideline is focused on, and should particularly consider whether chronic kidney
      disease is common in the target population. In contrast, potentially serious drug
      drug interactions between recommended drugs for different conditions were common.
      The extensive number of potentially serious interactions requires innovative
      interactive approaches to the production and dissemination of guidelines to allow
      clinicians and patients with multimorbidity to make informed decisions about drug
      selection.

PMID- 25762568
TI  - Multiple Phosphatases Regulate Carbon Source-Dependent Germination and Primary
      Metabolism in Aspergillus nidulans.
AB  - Aspergillus nidulans is an important mold and a model system for the study of
      fungal cell biology. In addition, invasive A. nidulans pulmonary infections are
      common in humans with chronic granulomatous disease. The morphological and
      biochemical transition from dormant conidia into active, growing, filamentous
      hyphae requires the coordination of numerous biosynthetic, developmental, and
      metabolic processes. The present study exhibited the diversity of roles performed
      by seven phosphatases in regulating cell cycle, development, and metabolism in
      response to glucose and alternative carbon sources. The identified phosphatases
      highlighted the importance of several signaling pathways regulating filamentous
      growth, the action of the pyruvate dehydrogenase complex as a metabolic switch
      controlling carbon usage, and the identification of the key function performed by
      the alpha-ketoglutarate dehydrogenase during germination. These novel insights
      into the fundamental roles of numerous phosphatases in germination and carbon
      sensing have provided new avenues of research into the identification of
      inhibitors of fungal germination, with implications for the food, feed, and
      pharmaceutical industries. 

PMID- 25762569
TI  - Sodium valproate increases the brain isoform of glycogen phosphorylase: looking
      for a compensation mechanism in McArdle disease using a mouse primary skeletal
      muscle culture in vitro.
AB  - McArdle disease, also termed 'glycogen storage disease type V', is a disorder of
      skeletal muscle carbohydrate metabolism caused by inherited deficiency of the
      muscle-specific isoform of glycogen phosphorylase (GP-MM). It is an autosomic
      recessive disorder that is caused by mutations in the PYGM gene and typically
      presents with exercise intolerance, i.e. episodes of early exertional fatigue
      frequently accompanied by rhabdomyolysis and myoglobinuria. Muscle biopsies from
      affected individuals contain subsarcolemmal deposits of glycogen. Besides GP-MM,
      two other GP isoforms have been described: the liver (GP-LL) and brain (GP-BB)
      isoforms, which are encoded by the PYGL and PYGB genes, respectively; GP-BB is
      the main GP isoform found in human and rat foetal tissues, including the muscle,
      although its postnatal expression is dramatically reduced in the vast majority of
      differentiated tissues with the exception of brain and heart, where it remains as
      the major isoform. We developed a cell culture model from knock-in McArdle mice
      that mimics the glycogen accumulation and GP-MM deficiency observed in skeletal
      muscle from individuals with McArdle disease. We treated mouse primary skeletal
      muscle cultures in vitro with sodium valproate (VPA), a histone deacetylase
      inhibitor. After VPA treatment, myotubes expressed GP-BB and a dose-dependent
      decrease in glycogen accumulation was also observed. Thus, this in vitro model
      could be useful for high-throughput screening of new drugs to treat this disease.
      The immortalization of these primary skeletal muscle cultures could provide a
      never-ending source of cells for this experimental model. Furthermore, VPA could
      be considered as a gene-expression modulator, allowing compensatory expression of
      GP-BB and decreased glycogen accumulation in skeletal muscle of individuals with
      McArdle disease. 

PMID- 25762571
TI  - Transgenerational effect of infection in Plasmodium-infected mosquitoes.
AB  - Transgenerational effects of infection have a huge potential to influence the
      prevalence and intensity of infections in vectors and, by extension, disease
      epidemiology. These transgenerational effects may increase the fitness of
      offspring through the transfer of protective immune factors. Alternatively,
      however, infected mothers may transfer the costs of infection to their offspring.
      Although transgenerational immune protection has been described in a dozen
      invertebrate species, we still lack a complete picture of the incidence and
      importance of transgenerational effects of infection in most invertebrate groups.
      The existence of transgenerational infection effects in mosquito vectors is of
      particular interest because of their potential for influencing parasite
      prevalence and intensity and, by extension, disease transmission. Here we present
      what we believe to be the first study on transgenerational infection effects in a
      mosquito vector infected with malaria parasites. The aim of this experiment was
      to quantify both the benefits and the costs of having an infected mother. We find
      no evidence of transgenerational protection in response to a Plasmodium
      infection. Having an infected mother does, however, entail considerable fecundity
      costs for the offspring: fecundity loss is three times higher in infected
      offspring issued from infected mothers than in infected offspring issued from
      uninfected mothers. We discuss the implications of our results and we call for
      more studies looking at transgenerational effects of infection in disease
      vectors.

PMID- 25762570
TI  - Adamtsl2 deletion results in bronchial fibrillin microfibril accumulation and
      bronchial epithelial dysplasia--a novel mouse model providing insights into
      geleophysic dysplasia.
AB  - Mutations in the secreted glycoprotein ADAMTSL2 cause recessive geleophysic
      dysplasia (GD) in humans and Musladin-Lueke syndrome (MLS) in dogs. GD is a
      severe, often lethal, condition presenting with short stature, brachydactyly,
      stiff skin, joint contractures, tracheal-bronchial stenosis and cardiac valve
      anomalies, whereas MLS is non-lethal and characterized by short stature and
      severe skin fibrosis. Although most mutations in fibrillin-1 (FBN1) cause Marfan
      syndrome (MFS), a microfibril disorder leading to transforming growth factor-beta
      (TGFbeta) dysregulation, domain-specific FBN1 mutations result in dominant GD.
      ADAMTSL2 has been previously shown to bind FBN1 and latent TGFbeta-binding
      protein-1 (LTBP1). Here, we investigated mice with targeted Adamtsl2 inactivation
      as a new model for GD (Adamtsl2(-/-) mice). An intragenic lacZ reporter in these
      mice showed that ADAMTSL2 was produced exclusively by bronchial smooth muscle
      cells during embryonic lung development. Adamtsl2(-/-) mice, which died at birth,
      had severe bronchial epithelial dysplasia with abnormal glycogen-rich inclusions
      in bronchial epithelium resembling the cellular anomalies described previously in
      GD. An increase in microfibrils in the bronchial wall was associated with
      increased FBN2 and microfibril-associated glycoprotein-1 (MAGP1) staining,
      whereas LTBP1 staining was increased in bronchial epithelium. ADAMTSL2 was shown
      to bind directly to FBN2 with an affinity comparable to FBN1. The observed
      extracellular matrix (ECM) alterations were associated with increased bronchial
      epithelial TGFbeta signaling at 17.5 days of gestation; however, treatment with
      TGFbeta-neutralizing antibody did not correct the epithelial dysplasia. These
      investigations reveal a new function of ADAMTSL2 in modulating microfibril
      formation, and a previously unsuspected association with FBN2. Our studies
      suggest that the bronchial epithelial dysplasia accompanying microfibril
      dysregulation in Adamtsl2(-/-) mice cannot be reversed by TGFbeta neutralization,
      and thus might be mediated by other mechanisms.

PMID- 25762572
TI  - Historical species losses in bumblebee evolution.
AB  - Investigating how species coped with past environmental changes informs how
      modern species might face human-induced global changes, notably via the study of
      historical extinction, a dominant feature that has shaped current biodiversity
      patterns. The genus Bombus, which comprises 250 mostly cold-adapted species, is
      an iconic insect group sensitive to current global changes. Through a combination
      of habitat loss, pathogens and climate change, bumblebees have experienced major
      population declines, and several species are threatened with extinction. Using a
      time-calibrated tree of Bombus, we analyse their diversification dynamics and
      test hypotheses about the role of extinction during major environmental changes
      in their evolutionary history. These analyses support a history of fluctuating
      species dynamics with two periods of historical species loss in bumblebees.
      Dating estimates gauge that one of these events started after the middle Miocene
      climatic optimum and one during the early Pliocene. Both periods are coincident
      with global climate change that may have extirpated Bombus species.
      Interestingly, bumblebees experienced high diversification rates during the Plio
      Pleistocene glaciations. We also found evidence for a major species loss in the
      past one million years that may be continuing today. 

PMID- 25762573
TI  - Mitochondrial genomes reveal the extinct Hippidion as an outgroup to all living
      equids.
AB  - Hippidions were equids with very distinctive anatomical features. They lived in
      South America 2.5 million years ago (Ma) until their extinction approximately 10
      000 years ago. The evolutionary origin of the three known Hippidion morphospecies
      is still disputed. Based on palaeontological data, Hippidion could have diverged
      from the lineage leading to modern equids before 10 Ma. In contrast, a much later
      divergence date, with Hippidion nesting within modern equids, was indicated by
      partial ancient mitochondrial DNA sequences. Here, we characterized eight
      Hippidion complete mitochondrial genomes at 3.4-386.3-fold coverage using target
      enrichment capture and next-generation sequencing. Our dataset reveals that the
      two morphospecies sequenced (H. saldiasi and H. principale) formed a monophyletic
      clade, basal to extant and extinct Equus lineages. This contrasts with previous
      genetic analyses and supports Hippidion as a distinct genus, in agreement with
      palaeontological models. We date the Hippidion split from Equus at 5.6-6.5 Ma,
      suggesting an early divergence in North America prior to the colonization of
      South America, after the formation of the Panamanian Isthmus 3.5 Ma and the Great
      American Biotic Interchange. 

PMID- 25762574
TI  - FDG positron emission tomography of giant cell arteritis with polymyalgia
      rheumatica.

PMID- 25762575
TI  - Malignant peripheral nerve sheath tumour (MPNST) of mandible: solving the
      perplexity.
AB  - We present an extremely rare case of malignant peripheral nerve sheath tumour
      (MPNST) in a 30-year-old woman without associated neurofibromatosis 1. The
      patient presented with an 8 cm*4 cm lesion extending from 46 to the retro molar
      region involving the ramus of the right mandible associated with regional
      paraesthesia. Incisional biopsy revealed spindle cells with vesicular nuclei
      arranged in fascicles leading to a diagnosis of spindle cell lesion. Posterior
      segmental mandibulectomy was performed under general anaesthesia. On excisional
      biopsy, a definitive diagnosis of low-grade MPNST was established on the basis of
      immunohistochemistry. The patient was then lost to follow-up.

PMID- 25762576
TI  - A case of endometriosis presenting as an inguinal hernia.
AB  - Endometriosis is a common clinical presentation for gynaecologists. Occasionally
      it can present to general surgeons as a swelling in the groin or abdominal wall.
      This condition should be included in the differential diagnosis in female
      patients. A 32-year-old woman with a 2-year history of a painful persistent lump
      in her right groin was referred to the general surgeons by her general
      practitioner. She was referred with a diagnosis of a suspected inguinal hernia.
      MRI excluded a hernia and exploration of the groin and subsequent histology
      confirmed the lesion to be an endometrial deposit. 

PMID- 25762577
TI  - Not a tragedy but a tool.

PMID- 25762578
TI  - Experiences of burden, needs, rewards and resilience in family caregivers of
      people living with Motor Neurone Disease/Amyotrophic Lateral Sclerosis: A
      secondary thematic analysis of qualitative interviews.
AB  - BACKGROUND: Family caregivers of people with Motor Neurone Disease/Amyotrophic
      Lateral Sclerosis, an incurable, mostly rapidly fatal neurodegenerative disease,
      face many challenges. Although there is considerable research on caregiver burden
      in Motor Neurone Disease/Amyotrophic Lateral Sclerosis, there is less knowledge
      of the positive aspects of caring. OBJECTIVE: To explore the experiences of
      family caregivers of people with Motor Neurone Disease/Amyotrophic Lateral
      Sclerosis, specifically the relationship between positive and negative
      experiences of caring, and to identify possible ways to better support these
      caregivers. METHODS: Secondary thematic analysis of 24 semi-structured
      qualitative interviews conducted longitudinally with 10 family caregivers.
      Interviews explored rewarding and unrewarding aspects of caring. RESULTS: Themes
      emerged around burden, needs, rewards and resilience. Resilience included getting
      active, retaining perspective and living for the moment. Burden was multifaceted,
      including social burden, responsibility, advocacy, ambivalence, guilt and
      struggling with acceptance. Rewards included being helped and 'ticking along'.
      Needs were multifaceted, including social, practical and psychological needs. The
      four main themes were interrelated. A model of coping was developed, integrating
      resilience (active/positive), burden (active/negative), needs (passive/negative)
      and reward (passive/positive). CONCLUSION: Burden, resilience, needs and rewards
      are interrelated. Caregivers' ability to cope with caring for a person with Motor
      Neurone Disease/Amyotrophic Lateral Sclerosis oscillates between positive and
      negative aspects of caring, being at times active, at times passive. CLINICAL
      IMPLICATIONS: Coping is a non-linear process, oscillating between different
      states of mind. The proposed model could enable clinicians to better understand
      the caregiver experience, help family caregivers foster resilience and identify
      rewards, and develop appropriate individualised caregiver support plans.

PMID- 25762579
TI  - Use of nasal fentanyl for cancer pain: A pharmacoepidemiological study.
AB  - BACKGROUND: Breakthrough pain affects 40%-90% of patients with cancer pain. Nasal
      fentanyl is one of the recommended treatments, particularly if the breakthrough
      pain is of rapid onset. AIM: To investigate the prevalence of use of nasal
      fentanyl, to study which strong opioids have been used prior to nasal fentanyl
      and to examine which opioids are used concomitantly with nasal fentanyl. DESIGN:
      Longitudinal cohort study based on death cohorts defined according to year of
      death. SETTING/PARTICIPANTS: The study is based on data from the complete
      national Norwegian Prescription Database. The study population included all
      persons in Norway who died in the years 2010, 2011 and 2012 and who had received
      nasal fentanyl with reimbursement for palliative treatment. RESULTS: Of those who
      died from cancer in 2010, 2011 and 2012, 611 persons (2%) received dispensed
      prescriptions of nasal fentanyl. Two-thirds had received other short-acting
      strong opioids before nasal fentanyl. One quarter did not receive a long-acting
      opioid concomitantly with nasal fentanyl, but 68% of these received only one
      dispensed prescription of nasal fentanyl. Of those who received a long-acting
      opioid together with nasal fentanyl, transdermal fentanyl was the most common
      drug (65%). One-third received another short-acting opioid concomitantly with
      nasal fentanyl. CONCLUSION: The use of nasal fentanyl was surprisingly low. There
      is a need for clinical research addressing the use of nasal fentanyl without a
      long-acting opioid for background pain and the use of nasal fentanyl together
      with another short-acting opioid.

PMID- 25762581
TI  - Perspectives on the role of the speech and language therapist in palliative care:
      An international survey.
AB  - BACKGROUND: Speech and language therapists can improve the quality of life of
      people receiving palliative care through the management of communication and
      swallowing difficulties (dysphagia). However, their role in this domain is poorly
      defined and little is understood about the current international professional
      practice in this field. AIMS: To examine how speech and language therapists
      perceive their role in the delivery of palliative care to clients, to discover
      current international speech and language therapist practices and to explore the
      similarities and differences in speech and language therapists' practice in
      palliative care internationally. This will inform professional clinical
      guidelines and practice in this area. DESIGN: Anonymous, non-experimental, cross
      sectional survey design. PARTICIPANTS: Speech and language therapists working
      with adult and paediatric palliative care populations in Republic of Ireland,
      United Kingdom, United States, Canada, Australia and New Zealand where the speech
      and language therapist profession is well established. METHOD: Purposive and
      snowball sampling were used to recruit participants internationally using
      gatekeepers. An online survey was disseminated using Survey Monkey
      (http://www.surveymonkey.com). RESULTS: A total of 322 speech and language
      therapists responded to the survey. Speech and language therapist practices in
      palliative care were similar across continents. Current speech and language
      therapist practices along with barriers and facilitators to practice were
      identified. The need for a speech and language therapist professional position
      paper on this topic was emphasised by respondents. CONCLUSION: Internationally,
      speech and language therapists believe they have a role in palliative care. The
      speech and language therapist respondents highlighted that this area of practice
      is under-resourced, under-acknowledged and poorly developed. They highlighted the
      need for additional research as well as specialist training and education for
      speech and language therapists and other multidisciplinary team members in the
      area of palliative care.

PMID- 25762580
TI  - Chronically homeless persons' participation in an advance directive intervention:
      A cohort study.
AB  - BACKGROUND: Chronically homeless individuals have high rates of hospitalization
      and death, and they may benefit from the completion of advance directives. AIM:
      To determine the rate of advance directive completion using a counselor-guided
      intervention, identify characteristics associated with advance directive
      completion, and describe end-of-life care preferences in a group of chronically
      homeless individuals. DESIGN: Participants completed a survey and were offered an
      opportunity to complete an advance directive with a trained counselor.
      PARTICIPANTS: A total of 205 residents of a shelter in Canada for homeless men
      (89.1% of those approached) participated from April to June 2013. RESULTS:
      Duration of homelessness was ?12 months in 72.8% of participants, and 103
      participants (50.2%) chose to complete an advance directive. Socio-demographic
      characteristics, health status, and health care use were not associated with
      completion of an advance directive. Participants were more likely to complete an
      advance directive if they reported thinking about death on a daily basis,
      believed that thinking about their friends and family was important, or reported
      knowing their wishes for end-of-life care but not having told anyone about these
      wishes. Among individuals who completed an advance directive, 61.2% named a
      substitute decision maker, and 94.1% expressed a preference to receive
      cardiopulmonary resuscitation in the event of a cardiorespiratory arrest if there
      was a chance of returning to their current state of health. CONCLUSION: A
      counselor-guided intervention can achieve a high rate of advance directive
      completion among chronically homeless persons. Most participants expressed a
      preference to receive cardiopulmonary resuscitation in the event of a
      cardiorespiratory arrest.

PMID- 25762584
TI  - Brain State Before Error Making in Young Patients With Mild Spastic Cerebral
      Palsy.
AB  - In the present experiment, children with mild spastic cerebral palsy and a
      control group carried out a memory recognition task. The key question was if
      errors of the patient group are foreshadowed by attention lapses, by weak motor
      preparation, or by both. Reaction times together with event-related potentials
      associated with motor preparation (frontal late contingent negative variation),
      attention (parietal P300), and response evaluation (parietal error-preceding
      positivity) were investigated in instances where 3 subsequent correct trials
      preceded an error. The findings indicated that error responses of the patient
      group are foreshadowed by weak motor preparation in correct trials directly
      preceding an error. 

PMID- 25762582
TI  - Genome-wide SNP identification for the construction of a high-resolution genetic
      map of Japanese flounder (Paralichthys olivaceus): applications to QTL mapping of
      Vibrio anguillarum disease resistance and comparative genomic analysis.
AB  - High-resolution genetic maps are essential for fine mapping of complex traits,
      genome assembly, and comparative genomic analysis. Single-nucleotide
      polymorphisms (SNPs) are the primary molecular markers used for genetic map
      construction. In this study, we identified 13,362 SNPs evenly distributed across
      the Japanese flounder (Paralichthys olivaceus) genome. Of these SNPs, 12,712 high
      confidence SNPs were subjected to high-throughput genotyping and assigned to 24
      consensus linkage groups (LGs). The total length of the genetic linkage map was
      3,497.29 cM with an average distance of 0.47 cM between loci, thereby
      representing the densest genetic map currently reported for Japanese flounder.
      Nine positive quantitative trait loci (QTLs) forming two main clusters for Vibrio
      anguillarum disease resistance were detected. All QTLs could explain 5.1-8.38% of
      the total phenotypic variation. Synteny analysis of the QTL regions on the genome
      assembly revealed 12 immune-related genes, among them 4 genes strongly associated
      with V. anguillarum disease resistance. In addition, 246 genome assembly
      scaffolds with an average size of 21.79 Mb were anchored onto the LGs; these
      scaffolds, comprising 522.99 Mb, represented 95.78% of assembled genomic
      sequences. The mapped assembly scaffolds in Japanese flounder were used for
      genome synteny analyses against zebrafish (Danio rerio) and medaka (Oryzias
      latipes). Flounder and medaka were found to possess almost one-to-one synteny,
      whereas flounder and zebrafish exhibited a multi-syntenic correspondence. The
      newly developed high-resolution genetic map, which will facilitate QTL mapping,
      scaffold assembly, and genome synteny analysis of Japanese flounder, marks a
      milestone in the ongoing genome project for this species. 

PMID- 25762583
TI  - Widespread anthelmintic resistance in European farmed ruminants: a systematic
      review.

PMID- 25762585
TI  - Outcome After Therapeutic Hypothermia in Term Neonates With Encephalopathy and a
      Syndromic Diagnosis.
AB  - The large randomized, controlled trials of therapeutic hypothermia for hypoxic
      ischemic encephalopathy excluded neonates with congenital disorders. The
      objective of this study was to report our experience using hypothermia in
      neonates with signs of hypoxic-ischemic encephalopathy and a syndromic disorder
      or brain anomaly. Subjects were identified from a database of neonates admitted
      to the Neuro-Intensive Care Nursery at University of California, San Francisco.
      Of 169 patients fulfilling criteria for hypothermia, 8 (5%) had a syndromic
      disorder and were cooled per guidelines for nonsyndromic neonates. Perinatal
      characteristics of infants with and without syndromic disorder were not
      significantly different. Overall outcome was poor: 38% had evidence of acute
      hypoxic-ischemic injury, 3 subjects died, and 2 survivors had low developmental
      quotient (ie, 25). The risk versus benefit of therapeutic hypothermia for hypoxic
      ischemic encephalopathy among neonates with congenital brain malformations or
      syndromic diagnoses is uncertain. 

PMID- 25762586
TI  - Intracranial Hypertension in Children: Etiologies, Clinical Features, and
      Outcome.
AB  - This retrospective study aimed to describe the clinical presentations, possible
      causes, and outcomes of children with idiopathic intracranial hypertension who
      presented to the authors' clinic. The mean age at onset of symptoms in the
      authors' cohort of 19 children was 6 years (range: 7 months to 12 years). Most
      patients (90%) were under 11 years old and (84.2%) symptomatic. The probable
      cause was identified in 7/19 (37.0%) patients. The most common cause was vitamin
      D deficiency (26.3%). Other associated probably coincidental comorbidities
      included sinusitis (5/19, 26.3%), hypophosphatasia (1/19), Pyle disease (1/19),
      and measles vaccine (1/19). Apart from 2 patients who required lumboperitoneal
      shunt, the cerebrospinal fluid pressure returned to normal in all patients within
      a period of 6 weeks to 1 year (average, 5 months). Of those who followed up with
      the authors' ophthalmologist, 30.7% developed optic atrophy or pallor; 75% of
      these patients had previous ocular comorbidities. 

PMID- 25762587
TI  - Resting State and Diffusion Neuroimaging Predictors of Clinical Improvements
      Following Constraint-Induced Movement Therapy in Children With Hemiplegic
      Cerebral Palsy.
AB  - The aim was to identify neuroimaging predictors of clinical improvements
      following constraint-induced movement therapy. Resting state functional magnetic
      resonance and diffusion tensor imaging data was acquired in 7 children with
      hemiplegic cerebral palsy. Clinical and magnetic resonance imaging (MRI) data
      were acquired at baseline and 1 month later following a 3-week constraint therapy
      regimen. A more negative baseline laterality index characterizing an atypical
      unilateral sensorimotor resting state network significantly correlated with an
      improvement in the Canadian Occupational Performance Measure score (r = -0.81, P
      = .03). A more unilateral network with decreased activity in the affected
      hemisphere was associated with greater improvements in clinical scores. Higher
      mean diffusivity in the posterior limb of the internal capsule of the affect
      tract correlated significantly with improvements in the Jebsen-Taylor score (r = 
      0.83, P = .02). Children with more compromised networks and tracts improved the
      most following constraint therapy. 

PMID- 25762588
TI  - Two Siblings With a CDKL5 Mutation: Genotype and Phenotype Evaluation.
AB  - This is the second report of a family with a recurrence of a CDKL5 mutation (c.
      283-3_290del) in 2 sisters. Both parents tested negative for the mutation in all
      tissues, but germline mosaicism is likely. Clinically CDKL5 patients resemble
      those with Rett syndrome, caused by a MECP2 mutation, who experience a
      regression, after an initial normal development. Even though both siblings showed
      a typical CDKL5 phenotype, their presentation is different. From birth, the
      oldest daughter had a severe developmental delay, feeding problems, and hypotonia
      and experienced daily refractory seizures. The youngest daughter appeared to be
      normal until age 3 months. At that age seizures started, deterioration and
      regression became evident, and an epileptic encephalopathy developed. This report
      of familial recurrence, with suspected germline mosaicism in a healthy parent,
      has important consequences for genetic counseling. Although it is not possible to
      predict an exact recurrence risk, it is likely to be increased. 

PMID- 25762589
TI  - Unsaturated fatty acid-induced non-canonical autophagy: unusual? Or
      unappreciated?
AB  - The breakdown of cellular components via autophagy is crucial for cellular
      homeostasis.In this issue of The EMBO Journal,Niso-Santano et al (2015) report
      the important observation that feeding cells with saturated or unsaturated fatty
      acids triggers mechanistically distinct autophagic responses. Feeding cells
      saturated fatty acid induced the canonical, BECN1/PI3K dependent autophagy
      pathway. Conversely,the unsaturated fatty acid oleate triggered autophagic
      responses that were independent of the BECN1/PI3K complex, but that required a
      functional Golgi system.

PMID- 25762590
TI  - Structural basis for a novel mechanism of DNA bridging and alignment in
      eukaryotic DSB DNA repair.
AB  - Eukaryotic DNA polymerase mu of the PolX family can promote the association of
      the two 3'-protruding ends of a DNA double-strand break (DSB) being repaired (DNA
      synapsis) even in the absence of the core non-homologous end-joining (NHEJ)
      machinery. Here, we show that terminal deoxynucleotidyltransferase (TdT), a
      closely related PolX involved in V(D)J recombination, has the same property. We
      solved its crystal structure with an annealed DNA synapsis containing one micro
      homology (MH) base pair and one nascent base pair. This structure reveals how the
      N-terminal domain and Loop 1 of Tdt cooperate for bridging the two DNA ends,
      providing a templating base in trans and limiting the MH search region to only
      two base pairs. A network of ordered water molecules is proposed to assist the
      incorporation of any nucleotide independently of the in trans templating base.
      These data are consistent with a recent model that explains the statistics of
      sequences synthesized in vivo by Tdt based solely on this dinucleotide step. Site
      directed mutagenesis and functional tests suggest that this structural model is
      also valid for Pol mu during NHEJ. 

PMID- 25762591
TI  - Presynapses go nuclear!
AB  - Decades of research has shown that long-term changes in synaptic function
      ultimately require changes in gene expression.Recent work has focused on nuclear
      signaling by calcium and protein messengers initiated at postsynaptic sites. In
      this issue of The EMBO Journal, Ivanova and colleagues show that shuttling of
      CtBP-1 between presynaptic areas and nuclei regulates gene expression, which
      reminds us that presynaptic zones should not be ignored when considering synapse
      to nucleus signaling.

PMID- 25762593
TI  - CD4 binding site broadly neutralizing antibody selection of HIV-1 escape mutants.
AB  - All human immunodeficiency virus type-1 (HIV-1) viruses use CD4 to enter cells.
      Consequently, the viral envelope CD4-binding site (CD4bs) is relatively
      conserved, making it a logical neutralizing antibody target. It is important to
      understand how CD4-binding site variation allows for escape from neutralizing
      antibodies. Alanine scanning mutagenesis identifies residues in antigenic sites,
      whereas escape mutant selection identifies viable mutants. We selected HIV-1 to
      escape CD4bs neutralizing mAbs b12, A12 and HJ16. Viruses that escape from A12
      and b12 remained susceptible to HJ16, VRC01 and J3, whilst six different viruses
      that escape HJ16 remained sensitive to A12, b12 and J3. In contrast, their
      sensitivity to VRC01 was variable. Triple HJ16/A12/b12-resistant virus proved
      that HIV-1 could escape multiple broadly neutralizing monoclonal antibodies, but
      still retain sensitivity to VRC01 and the llama-derived J3 nanobody. This
      antigenic variability may reflect that occurring in circulating viruses, so
      studies like this can predict immunologically relevant antigenic forms of the
      CD4bs for inclusion in HIV-1 vaccines. 

PMID- 25762595
TI  - [Mass spectrometry analysis of blood plasma lipidome as method of disease
      diagnostics, evuation of effectiveness and optimization of drug therapy].
AB  - A new method for the analysis of blood lipid based on direct mass spectrometry of
      lipophilic low molecular weight fraction of blood plasma has been considered.
      Such technique allows quantification of hundreds of various types of lipids and
      this changes existing concepts on diagnostics of lipid disorders and related
      diseases. The versatility and quickness of the method significantly simplify its
      wide use. This method is applicable for diagnostics of atherosclerosis, diabetes,
      cancer and other diseases. Detalization of plasma lipid composition at the
      molecular level by means of mass spectrometry allows to assess the effectiveness
      of therapy and to optimize the drug treatment of cardiovascular diseases by
      phospholipid preparations. 

PMID- 25762594
TI  - Mesenchymal dental pulp cells attenuate dentin resorption in homeostasis.
AB  - Dentin in permanent teeth rarely undergoes resorption in development,
      homeostasis, or aging, in contrast to bone that undergoes periodic
      resorption/remodeling. The authors hypothesized that cells in the mesenchymal
      compartment of dental pulp attenuate osteoclastogenesis. Mononucleated and
      adherent cells from donor-matched rat dental pulp (dental pulp cells [DPCs]) and
      alveolar bone (alveolar bone cells [ABCs]) were isolated and separately
      cocultured with primary rat splenocytes. Primary splenocytes readily aggregated
      and formed osteoclast-like cells in chemically defined osteoclastogenesis medium
      with 20 ng/mL of macrophage colony-stimulating factor (M-CSF) and 50 ng/mL of
      receptor activator of nuclear factor kappaB ligand (RANKL). Strikingly, DPCs
      attenuated osteoclastogenesis when cocultured with primary splenocytes, whereas
      ABCs slightly but significantly promoted osteoclastogenesis. DPCs yielded ~20
      fold lower RANKL expression but >2-fold higher osteoprotegerin (OPG) expression
      than donor-matched ABCs, yielding a RANKL/OPG ratio of 41:1 (ABCs:DPCs). Vitamin
      D3 significantly promoted RANKL expression in ABCs and OPG in DPCs. In vivo, rat
      maxillary incisors were atraumatically extracted (without any tooth fractures),
      followed by retrograde pulpectomy to remove DPCs and immediate replantation into
      the extraction sockets to allow repopulation of the surgically treated root canal
      with periodontal and alveolar bone-derived cells. After 8 wk, multiple
      dentin/root resorption lacunae were present in root dentin with robust RANKL and
      OPG expression. There were areas of dentin resoprtion alternating with areas of
      osteodentin formation in root dentin surface in the observed 8 wk. These findings
      suggest that DPCs of the mesenchymal compartment have an innate ability to
      attenuate osteoclastogenesis and that this innate ability may be responsible for
      the absence of dentin resorption in homeostasis. Mesenchymal attenuation of
      dentin resorption may have implications in internal resorption in the root canal,
      pulp/dentin regeneration, and root resorption in orthodontic tooth movement. 

PMID- 25762596
TI  - [Prospects for use of peptides and their derivatives, structurally corresponding
      to the G protein-coupled receptors, in medicine].
AB  - The regulation of signaling pathways involved in the control of many
      physiological functions is carried out via the heterotrimeric G protein-coupled
      receptors (GPCR). The search of effective and selective regulators of GPCR and
      intracellular signaling cascades coupled with them is one of the important
      problems of modern fundamental and clinical medicine. Recently data suggest that
      synthetic peptides and their derivatives, structurally corresponding to the
      intracellular and transmembrane regions of GPCR, can interact with high
      efficiency and selectivity with homologous receptors and influence, thus, the
      functional activity of intracellular signaling cascades and fundamental cellular
      processes controlled by them. GPCR-peptides are active in both in vitro and in
      vivo. They regulate hematopoiesis, angiogenesis and cell proliferation, inhibit
      tumor growth and metastasis, and prevent the inflammatory diseases and septic
      shock. These data show greatest prospects in the development of the new
      generations of drugs based on GPCR-derived peptides, capable of regulating the
      important functions of the organism. 

PMID- 25762592
TI  - Chemokine-guided cell migration and motility in zebrafish development.
AB  - Chemokines are vertebrate-specific, structurally related proteins that function
      primarily in controlling cell movements by activating specific 7-transmembrane
      receptors. Chemokines play critical roles in a large number of biological
      processes and are also involved in a range of pathological conditions. For these
      reasons, chemokines are at the focus of studies in developmental biology and of
      clinically oriented research aimed at controlling cancer, inflammation, and
      immunological diseases. The small size of the zebrafish embryos, their rapid
      external development, and optical properties as well as the large number of eggs
      and the fast expansion in genetic tools available make this model an extremely
      useful one for studying the function of chemokines and chemokine receptors in an
      in vivo setting. Here, we review the findings relevant to the role that
      chemokines play in the context of directed single-cell migration, primarily in
      neutrophils and germ cells, and compare it to the collective cell migration of
      the zebrafish lateral line. We present the current knowledge concerning the
      formation of the chemokine gradient, its interpretation within the cell, and the
      molecular mechanisms underlying the cellular response to chemokine signals during
      directed migration.

PMID- 25762597
TI  - [Preparation of dendritic cells for cancer immunotherapy].
AB  - Development of new effective method for cancer therapy is one of the most
      important trends in the modern medicine. Along with surgery, chemotherapy and
      radiotherapy, induction of an immune response against the tumor cells is a
      promising approach for therapy of cancer, particularly metastatic, slowly
      dividing tumors and cancer stem cells. Induction of the antitumor T-cell immune
      response involves activation of antigen-presenting cells, which can efficiently
      present the cancer antigens and activate T-lymphocytes. The immune response may
      be activated by dendritic cells (DC) loaded with tumor antigens, such as tumor
      specific proteins, tumor cell lysates, apoptotic or necrotic tumor cells, as well
      as nucleic acids encoding tumor antigens. Regardless of the selected source of
      the tumor antigen, preparation of mature DC is a principal step in the
      development of anticancer vaccines aimed at the induction of the cytotoxic T-cell
      immune response. Recently, various research groups have proposed several
      strategies for producing mature DC, differed by the set of agents used. It has
      been shown that the maturation strategy influences both their phenotype and the
      ability to induce the immune response. In this review we have analyzed the
      results of studies on the various strategies of preparation of mature DCs. 

PMID- 25762598
TI  - [Role of angiostatins in diabetic complications].
AB  - Angiogenesis is a process through which new blood vessels form from pre-existing
      vessels. Angiogenesis is regulated by a number of factors of peptide nature.
      Disbalance of angiogenic system appears to be the major causative factor
      contributing vascular abnormalities in diabetes mellitus, resulting in various
      complications. Angiostatins, which are kringle-containing fragments of
      plasminogen/plasmin, are known to be powerful physiological inhibitors of
      neovascularization. In the present review, current literature data on
      peculiarities of production of angiostatins and their functioning at diabetes
      mellitus are summarized and analyzed for the first time. Also, role of
      angiostatins in the pathogenesis of typical diabetic complications, including
      retinopathies, nephropathies and cardiovascular diseases, is discussed. Data
      presented in this review may be useful for elaboration of novel effective
      approaches for diagnostics and therapy of vascular abnormalities in diabetes
      mellitus. 

PMID- 25762599
TI  - [Oxidative stress and its effect on cells functional activity of alzheimer's
      disease].
AB  - The paper summarizes literature data on the importance of oxidative stress as one
      of the pathogenetic mechanisms in Alzheimer's disease. The paper describes the
      main specific and nonspecific ways of reactive oxygen species generation in the
      course of the disease development. The effect of reactive oxygen species
      generated by the functional activity of cells, i.e. apoptosis and mitotic cycle,
      is shown. The role of the regulatory system of nodal cells is performed by
      phosphorylation/dephosphorylation process which is associated with intense
      phosphorylation of tau protein and mitosis-specific proteins. In Alzheimer's
      disease, the regulating function of peptidyl-prolyl isomerases in particular of
      Pin1 associated with maintaining a balanced state of
      phosphorylation/dephosphorylation processes is disturbed. Taking into
      consideration the multifactorial impairment of the cell cycle control, this
      process should be considered from the standpoint of the general state of
      metabolic processes, and oxidative stress has one of the key positions in aging. 

PMID- 25762600
TI  - [Insulin resistance pathogenesis in metabolic obesity].
AB  - In this review we discuss the molecular mechanisms of insulin resistance
      concomitant with metabolic inflammation. We also analyze the world results of
      experimental and clinical studies which aimed at identifying the molecular
      targets for the development of new prevention and treatment of insulin
      resistance. 

PMID- 25762601
TI  - [pIPredict: a computer tool for predicting isoelectric points of peptides and
      proteins].
AB  - The data on approximate values of isoelectric point (pI) of peptides obtained
      during their fractionation by isoelectric focusing can be successfully used for
      the calculation of the pKa's scale for amino acid residues. This scale can be
      used for pI prediction. The data of peptide fractionation also provides
      information about various posttranslational modifications (PTM), so that the
      prediction of pI may be performed for a wide range of protein forms. In this
      study, pKa values were calculated using a set of 13448 peptides (including 300
      peptides with PTMs significant for pI calculation). The pKa constants were
      calculated for N-terminal, internal and C-terminal amino acid residues
      separately. The comparative analysis has shown that our scale increases the
      accuracy of pI prediction for peptides and proteins and successfully competes
      with traditional scales and such methods as support vector machines and
      artificial neural networks. The prediction performed by this scale, can be made
      in our program pIPredict with GUI written in JAVA as executable jar-archive. The
      program is freely available for academic users at
      http://www.ibmc.msk.ru/LPCIT/pIPredict. The software has also the possibility of
      pI predicting by some other scales; it recognizes some PTM and has the ability to
      use a custom scale. 

PMID- 25762602
TI  - [Changes in proteome profiles of rat liver microsomes induced by silicon dioxide
      nanoparticles].
AB  - The effect of daily intragastric administration of an aqueous dispersion of
      silicon nanoparticles (NPs) (the dose range from 1.0 mg/kg to 100 mg/kg body
      weight for 28 days) to rats on the proteomic profile of liver microsomes has been
      investigated by 2D-electrophoresis followed by subsequent mass spectrometry
      identification. The liver microsomal fraction was isolated by differential
      centrifugation and its protein composition was analyzed by 2D-polyacrylamide gel
      electrophoresis. Identification of protein spots was carried out using MALDI-TOF
      mass spectrometric analysis. The mass spectrometry analysis revealed the protein
      GRP78 (78 kD glucose-regulated protein precursor), belonging to the family of
      heat shock proteins. This protein present in animals of the control group was not
      detected in NP-treated rats of group 2 (1 mg/kg body weight/day) and group 3 (10
      mg/kg body weight/day). This protein predominantly localized in the liver cell
      endoplasmic reticulum and plasma membrane has the chaperone biological activity.
      Possible mechanisms of the effects of engineered nanoparticles on biosynthetic
      processes in the body are discussed. 

PMID- 25762603
TI  - [Effect of L-lysine alpha-oxidase from Trichoderma cf. aureoviride Rifai VKMF
      4268D on pheochromocytoma PC12 cell line].
AB  - L-Amino acid oxidases (L-AAO, EC 1.4.3.2) comprise a group of flavoproteins,
      catalyzing oxidative deamination of L-alpha amino acids to the corresponding
      alpha-keto acids, NH3 and N2O2. In most cases these enzymes present homodimeric
      molecules with a molecular mass of 100-150 kDa, which were shown to possess
      antiviral, antifungal and antitumor activity. L-lysine alpha-oxidase (LO) holds
      an outstanding place among this group of enzymes and its biological role may
      differ significantly from the other L-AAO, because it cleaves an essential amino
      acid - L-lysine without significant action on the other amino acids. Although
      much research has examined LO effects in the organism, the molecular basis of
      these effects is yet to be identified. To fill this gap, the present work
      addressed one of hypothetical mechanisms of LO biological action using the enzyme
      from Trichoderma cf. aureoviride Rifai VKMF-4268D and rat pheochromocytoma PC-12
      as a model cell line. Using flow cytometry a dose-dependent cytotoxicity of LO
      was shown. The significant growth of intracellular reactive oxygen species
      levels, detected by 2,7-dichlorodihydrofluorescein assay, implies generation of
      peroxide as one of the molecular mechanisms of LO cytotoxic action, although this
      does not rule out other probable ways of LO action in the organizm. 

PMID- 25762604
TI  - [The metabolism of the innate immunity cells in bacterial infections].
AB  - Metabolic activity of innate immunity cells infected by various doses of Gram
      negative (Yersinia pseudotuberculosis, Salmonella enteritidis) and Gram-positive
      (Staphylococcus aureus, Listeria monocytogenes) bacteria has been investigated.
      Using various animal models we found that during the initial period (up to 2
      days) changes of infection in cellular responses depend on the type of the
      pathogen. In response to infection caused by Gram-negative bacteria predominant
      neutrophil accumulation in the foci of inflammation was observed, while Gram
      positive bacteria induced preferential accumulation of macrophages. The study of
      metabolism of these cells showed that the response of terminally differentiated
      primed phagocytes to pathogen appearance was higher than in cells circulating in
      blood. In addition to the priming state the phagocyte reactivity is influenced by
      the bacterial load. At a low phagocyte/microbe ratio the cells reaction is almost
      undetectable, while an excess of microorganisms causes (despite of the increase
      of the phagocytic parameters) the hyperactivation of cell metabolism and
      production of maximal amounts of bactericide agents, which exhibit a damaging
      effect on the cell itself. 

PMID- 25762605
TI  - [Involvement of carbonate/bicarbonate ions in the superoxide-generating reaction
      of adrenaline autoxidation].
AB  - An important role of carbonate/bicarbonate ions has been recognized in the
      superoxide generating reaction of adrenaline autooxidation in an alkaline buffer
      (a model of quinoid adrenaline oxidation in the body). It is suggested that these
      ions are directly involved not only in formation of superoxide anion radical
      (O(2)(-)) but also other radicals derived from the carbonate/bicarbonate buffer.
      Using various buffers it was shown that the rate of accumulation of adrenochrome,
      the end product of adrenaline oxidation, and the rate of O(2)(-). formation
      depend on concentration of carbonate/bicarbonate ions in the buffer and that
      these ions significantly accelerate adrenaline autooxidation thus demonstrating
      prooxidant properties. The detectable amount of diformazan, the product of nitro
      blue tetrazolium (NBT) reduction, was significantly higher than the amount of
      adrenochrome formed; taking into consideration the literature data on O(2)(-).
      detection by NBT it is suggested that adrenaline autooxidation is accompanied by
      one-electron reduction not only of oxygen dissolved in the buffer and responsible
      for superoxide formation but possible carbon dioxide also dissolved in the buffer
      as well as carbonate/bicarbonate buffer components leading to formation of
      corresponding radicals. The plots of the dependence of the inhibition of
      adrenochrome and diformazan formation on the superoxide dismutase concentration
      have shown that not only superoxide radicals are formed during adrenaline
      autooxidation. Since carbonate/bicarbonate ions are known to be universally
      present in the living nature, their involvement in free radical processes
      proceeding in the organism is discussed.

PMID- 25762606
TI  - [Hplc estimation of coenzyme Q(10) redox status in plasma after intravenous
      coenzyme Q(10) administration].
AB  - The pharmacokinetics of the total pool of coenzyme Q(10) (Co(10)), its oxidized
      (ubiquinone) and reduced (ubiquinol, CoQ(10)H2) forms have been investigated in
      rats plasma during 48 h after a single intravenous injection of a solution of
      solubilized CoQ(10) (10 mg/kg) to rats. Plasma levels of CoQ(10) were determined
      by HPLC with spectrophotometric and coulometric detection. In plasma samples
      taken during the first minutes after the CoQ(10) intravenous injection, the total
      pool of coenzyme Q(10) and proportion of CoQ(10)H2 remained unchanged during two
      weeks of storage at -20 degrees C. The kinetic curve of the total pool of
      coenzyme Q(10) corresponds to a one-part model (R2 = 0.9932), while the
      corresponding curve of its oxidized form fits to the two-part model. During the
      first minutes after the injection a significant portion of plasma ubiquinone
      undergoes reduction, and after 7 h the concentration of ubiquinol predominates.
      The decrease in the total plasma coenzyme Q(10) content was accompanied by the
      gradual increase in plasma ubiquinol, which represented about 90% of total plasma
      CoQ(10) by the end of the first day. The results of this study demonstrate the
      ability of the organism to transform high concentrations of the oxidized form of
      CoQ(10) into the effective antioxidant (reduced) form and justify prospects of
      the development of parenteral dosage forms of CoQ(10) for the use in the
      treatment of acute pathological conditions.

PMID- 25762607
TI  - [Modeling role of pyruvate in the processes of protein-protein interaction].
AB  - Using the ABO antibody-antigen model the influence of natural metabolite pyruvate
      on the antibody interaction with of erythrocyte antigens, defining their group
      specificity has been investigated. Before agglutination reaction erythrocytes of
      A(II)-AB(IV) blood groups, monoclonal anti-A and anti-B antibodies were incubated
      with sodium pyruvate. Visualization of agglutinates was performed by means of
      flow cytometry and laser scanning confocal microscopy. Computer-aided prediction
      of the spectrum of biological activity of pyruvate by a PASS program proposed
      major regulatory pathways, in which pyruvate may be involved. It has been
      demonstrated that pyruvate can regulate the intensity of antigen-antibody
      interaction. These results suggest the possibility of using small molecules, for
      example pyruvate, as molecular probes and prospects of the use of erythrocytes
      with antigenic determinants of the ABO system expressed on their membranes for
      studies of protein-protein interactions due to convenient visualization and
      possibility of quantitative evaluation of this process. 

PMID- 25762608
TI  - [NMR study of human biological fluids for detection of pathologies].
AB  - The paper deals with the NMR spectra obtained using preparations of five
      different human biological body fluids. Characteristic metabolite signals of
      blood, urine, tears, saliva, and sweat spectra have been determined and
      classified. The biological body fluid samples were used for search and
      identification of biomarkers of cardiovascular disease. Absolute functional
      biomarkers for diseases such as coronary heart disease (CHD) have not been
      recognized even in the case acute myocardial infarction. A hypothesis explaining
      reasons of lack of such markers has been formulated. The results of comparative
      analysis of blood and urine samples from humans and some laboratory animals are
      given. Identify and analyze signals of metabolites of pathogenic microflora and
      their dynamics in the urine from patients with urogenital diseases have been
      determined and analyzed and characteristic biomarkers have been recognized. 

PMID- 25762609
TI  - [Development of noninvasive bladder cancer diagnosis on basis of telomerase and
      it's subunits hTERT and hTR detection].
AB  - Telomerase activity (TA) and expression of genes coding it's subunits (hTERT and
      hTR) have been examined in tumor tissue and urine sediment samples taken from
      patients with bladder cancer (BC) using the modified TRAP assay (in the case of
      telomerase detection) and RT-PCR (in the case of hTERT and hTR expression).
      Results obtained in this study demonstrate possibility of noninvasive diagnosis
      of BC with sensitivity of 96% and specificity of 100% in the case of telomerase
      detection and with sensitivity of 80% and specificity of 100% in the case of
      hTERT detection in urine sediment samples. 

PMID- 25762610
TI  - Mild Cognitive Impairment Subtypes in Older People With Depressive Symptoms:
      Relationship With Clinical Variables and Hippocampal Change.
AB  - AIMS: To examine the rates and clinical characteristics of mild cognitive
      impairment (MCI) in older people with depressive symptoms and to determine the
      relative contribution of hippocampal volume and MCI to memory change. METHOD: One
      hundred and fifty-two participants with lifetime Major Depression and remitted or
      mild symptoms and 28 healthy controls underwent psychiatric and
      neuropsychological assessments. Magnetic resonance imaging was also conducted in
      a subset of the patients (n = 81) and healthy controls (n = 18). RESULTS: MCI was
      diagnosed in 75.7% of the patients and was associated with increasing age,
      medical burden, vascular risk factors, later age of depression onset and smaller
      hippocampi. Multiple regression showed that both hippocampal volume and MCI
      diagnosis mediate memory performance in depression. CONCLUSIONS: MCI occurs in
      older adults with a history of depression and is not simply due to symptom
      severity. Memory change is linked to underlying hippocampal atrophy in this
      patient group.

PMID- 25762611
TI  - Evaluation of an instrument-assisted dynamic prosthetic alignment technique for
      individuals with transtibial amputation.
AB  - BACKGROUND: A prosthesis that is not optimally aligned can adversely influence
      the rehabilitation and health of the amputee. Very few studies to date evaluate
      the effectiveness and utility of instrument-assisted alignment techniques in
      clinical practice. OBJECTIVES: To compare an instrument-assisted dynamic
      alignment technique (Compas(TM)) to conventional methods. STUDY DESIGN: In a
      crossover study design, dynamic prosthetic alignments were provided to nine
      individuals with unilateral transtibial amputations to compare conventional and
      instrument-assisted alignment techniques. METHODS: The instrument-assisted
      technique involved a commercially available force and torque sensing dynamic
      alignment system (Compas). Cadence, pelvic accelerations, and socket moments were
      assessed. A custom questionnaire was used to gather user perceptions. RESULTS: No
      differences between alignment techniques were found in global gait measures
      including cadence and pelvic accelerations. No significant alignment differences
      were achieved by examination of angular changes between the socket and foot;
      however, significantly higher below-the-socket moments were found with the
      instrument-assisted technique. From the questionnaire, six amputees had no
      preference, while three preferred the conventional alignment. CONCLUSION: The use
      of Compas appears to produce similar alignment results as conventional
      techniques, although with slightly higher moments at the socket. CLINICAL
      RELEVANCE: This study provides new information about the clinical utilization of
      instrument-assisted prosthetic alignment techniques for individuals with
      transtibial amputation.

PMID- 25762612
TI  - Dilatancy-based impression and fabrication technique for custom foot orthoses.
AB  - BACKGROUND AND AIM: Current methods used to take impressions for custom foot
      orthoses include plaster bandage, foam box, fiberglass, and laser-optical
      scanner. Impressions are converted to positive plaster or foam models. These
      methods create waste and may not be feasible in resource-limited areas. This
      technical note presents an alternative, greener impression and fabrication
      technique for foot orthoses that utilizes the dilatancy principle. TECHNIQUE:
      Steps of the dilatancy (vacuum-based) procedure include taking an impression of
      the foot, converting the negative mold to a positive sand model, modifying the
      positive sand model, and thermoforming the foot orthosis. DISCUSSION: This
      plaster-less system is inexpensive to set up and maintain, is reusable thereby
      minimizing cost and waste, and is clean to use. It enables a practitioner to
      quickly take an impression for fabricating a foot orthosis in a short period of
      time during a single clinic visit by the patient. CLINICAL RELEVANCE: The
      dilatancy casting system could potentially be a cheaper, faster, and greener
      alternative procedure for fabricating custom foot orthoses in both developing and
      developed countries.

PMID- 25762613
TI  - Pneumatic-type dynamic traction and flexion splint for treating patients with
      extension contracture of the metacarpophalangeal joint.
AB  - BACKGROUND: Collateral ligament shortening causes extension contractures of the
      metacarpophalangeal joint, and dynamic flexion splinting has been widely used to
      treat these contractures; however, there are various problems with these
      approaches. We developed a novel, pneumatic-type dynamic traction and flexion
      splint to solve these problems. CASE DESCRIPTION AND METHODS: A total of 25
      fingers were treated with the dynamic traction and flexion splint for 8 weeks.
      Every 2 weeks, the average metacarpophalangeal joint flexion angle, total active
      motion, grasp strength, and pain scores were assessed. FINDINGS AND OUTCOMES: The
      finger flexion angle was significantly greater at the final evaluation, starting
      after 6 weeks of treatment (p < 0.05), than prior to treatment. Similarly, the
      total active motion results improved significantly over 8 weeks. CONCLUSIONS: Our
      results show that use of the dynamic traction and flexion splint improves patient
      finger functioning and flexural angle. CLINICAL RELEVANCE: The dynamic traction
      and flexion (DTF) splint appears to be effective for treating patients.

PMID- 25762614
TI  - Practical guidelines for fabricating mandibular guide flange prostheses: A new
      technique for measuring the flange angulation.
AB  - BACKGROUND AND AIM: When a mandibulectomy causes discontinuity, the patient will
      need a rehabilitative prosthesis to achieve a proper occlusal relationship.
      TECHNIQUE: This article describes step-by-step guidelines for measuring the
      patient-specific mandibular guide flange angulation. In the presented technique,
      the flange angulation is determined by dividing the horizontal overlap of the
      maxillary posterior teeth plus the maxillary buccal clasp thickness by the
      vertical distance of the mandibular continuous clasp up to the maxillary buccal
      clasp. DISCUSSION: The mandibular guiding flange prosthesis must achieve an
      angulation that is appropriate for the particular circumstances of each patient
      to minimize the complications with mandibular deviation. CLINICAL RELEVANCE: The
      introduced method for measuring the patient-specific mandibular guide flange
      angulation can help prosthodontists to prepare the mandibular guiding flange
      prosthesis with higher accuracy and predictability.

PMID- 25762615
TI  - Anti-BDCA2 monoclonal antibody inhibits plasmacytoid dendritic cell activation
      through Fc-dependent and Fc-independent mechanisms.
AB  - Type I interferons (IFN-I) are implicated in the pathogenesis of systemic lupus
      erythematosus (SLE). In SLE, immune complexes bind to the CD32a (FcgammaRIIa)
      receptor on the surface of plasmacytoid dendritic cells (pDCs) and stimulate the
      secretion of IFN-I from pDCs. BDCA2 is a pDC-specific receptor that, when
      engaged, inhibits the production of IFN-I in human pDCs. BDCA2 engagement,
      therefore, represents an attractive therapeutic target for inhibiting pDC-derived
      IFN-I and may be an effective therapy for the treatment of SLE. In this study, we
      show that 24F4A, a humanized monoclonal antibody (mAb) against BDCA2, engages
      BDCA2 and leads to its internalization and the consequent inhibition of TLR
      induced IFN-I by pDCs in vitro using blood from both healthy and SLE donors.
      These effects were confirmed in vivo using a single injection of 24F4A in
      cynomolgus monkeys. 24F4A also inhibited pDC activation by SLE-associated immune
      complexes (IC). In addition to the inhibitory effect of 24F4A through engagement
      of BDCA2, the Fc region of 24F4A was critical for potent inhibition of IC-induced
      IFN-I production through internalization of CD32a. This study highlights the
      novel therapeutic potential of an effector-competent anti-BDCA2 mAb that
      demonstrates a dual mechanism to dampen pDC responses for enhanced clinical
      efficacy in SLE.

PMID- 25762617
TI  - Inhibition of DNA methyltransferase as a novel therapeutic strategy to overcome
      acquired resistance to dual PI3K/mTOR inhibitors.
AB  - Dual PI3K/mTOR(phosphatidylinositol 3-kinase/mammalian target of rapamycin)
      inhibitors are being evaluated clinically for the treatment of tumors with a
      hyperactivated PI3K/mTOR pathway. However, unexpected outcomes were obtained in
      clinical studies of cancer patients with an aberrant PI3K pathway. In clinical
      trials, applicable combination regimens are not yet available. In this study,
      using an integrated analysis of acquired BEZ235-resistant nasopharyngeal
      carcinoma cells, we demonstrate that DNA methyltransferase is a key modulator and
      a common node upstream of the AKT/mTOR and PDK1/MYC pathways, which are activated
      in cancer cells with acquired BEZ235 resistance. DNA methyltransferases were
      upregulated and induced PTEN and PPP2R2B gene hypermethylation, which
      downregulated their expression in BEZ235-resistant cancer cells. Reduced PTEN and
      PPP2R2B expression correlated with activated AKT/mTOR and PDK1/MYC pathways and
      conferred considerable BEZ235 resistance in nasopharyngeal carcinoma. Targeting
      methyltransferases in combination with BEZ235 sensitized BEZ235-resistant cells
      to BEZ235 in vitro and in vivo, suggesting the potential clinical application of
      this strategy to overcome BEZ235 resistance. 

PMID- 25762618
TI  - SRC family kinase (SFK) inhibition reduces rhabdomyosarcoma cell growth in vitro
      and in vivo and triggers p38 MAP kinase-mediated differentiation.
AB  - Recent data suggest that SRC family kinases (SFKs) could represent potential
      therapeutic targets for rhabdomyosarcoma (RMS), the most common soft-tissue
      sarcoma in children. Here, we assessed the effect of a recently developed
      selective SFK inhibitor (a pyrazolo[3,4-d]pyrimidine derivative, called SI221) on
      RMS cell lines. SI221, which showed to be mainly effective against the SFK member
      YES, significantly reduced cell viability and induced apoptosis, without
      affecting non-tumor cells, such as primary human skin fibroblasts and
      differentiated C2C12 cells. Moreover, SI221 decreased in vitro cell migration and
      invasion and reduced tumor growth in a RMS xenograft model. SFK inhibition also
      induced muscle differentiation in RMS cells by affecting the NOTCH3 receptor-p38
      mitogen-activated protein kinase (MAPK) axis, which regulates the balance between
      proliferation and differentiation. Overall, our findings suggest that SFK
      inhibition, besides reducing RMS cell growth and invasive potential, could also
      represent a differentiation therapeutic strategy for RMS. 

PMID- 25762616
TI  - Garcinol sensitizes human head and neck carcinoma to cisplatin in a xenograft
      mouse model despite downregulation of proliferative biomarkers.
AB  - Platinum compounds such as cisplatin and carboplatin are frequently used as the
      first-line chemotherapy for the treatment of the head and neck squamous cell
      carcinoma (HNSCC). In the present study, we investigated whether garcinol, a
      polyisoprenylated benzophenone can chemosensitize HNSCC to cisplatin. We found
      that garcinol inhibited the viability of a panel of diverse HNSCC cell lines,
      enhanced the apoptotic effect of cisplatin, suppressed constitutive as well as
      cisplatin-induced NF-kappaB activation, and downregulated the expression of
      various oncogenic gene products (cyclin D1, Bcl-2, survivin and VEGF). In vivo
      study showed that administration of garcinol alone (0.5 mg/kg body weight, i.p.
      five times/week) significantly suppressed the growth of the tumor, and this
      effect was further increased by cisplatin. Both the markers of proliferation
      index (Ki-67) and microvessel density (CD31) were downregulated in tumor tissues
      by the combination of cisplatin and garcinol. The pharmacokinetic results of
      garcinol indicated that good systemic exposure was achievable after i.p.
      administration of garcinol at 0.5 mg/kg and 2 mg/kg with mean peak concentration
      (Cmax) of 1825.4 and 6635.7 nM in the mouse serum, respectively. Overall, our
      results suggest that garcinol can indeed potentiate the effects of cisplatin by
      negative regulation of various inflammatory and proliferative biomarkers. 

PMID- 25762620
TI  - Up-regulation of C1GALT1 promotes breast cancer cell growth through MUC1-C
      signaling pathway.
AB  - Aberrant glycosylation is frequently observed in cancers. Core 1 beta1,3
      galactosyltransferase (C1GALT1) is an exclusive enzyme in humans that catalyzes
      the biosynthesis of core 1 O-glycan structure, Gal-GalNAc-O-Ser/Thr, whose
      expression is commonly up-regulated during tumorigenesis. Little is known about
      the function of C1GALT1 in breast cancer. This study aims to determine the
      correlation between C1GALT1 expression and breast cancer clinicopathological
      features and roles of C1GALT1 in breast cancer malignant phenotypes. Public
      databases and our data showed that C1GALT1 mRNA and C1GALT1 protein are
      frequently up-regulated in breast cancer; and increased C1GALT1 expression
      correlates with higher histological grade and advanced tumor stage.
      Overexpression of C1GALT1 enhanced breast cancer cell growth, migration, and
      invasion in vitro as well as tumor growth in vivo. Conversely, C1GALT1 knockdown
      suppressed these malignant phenotypes. Furthermore, C1GALT1 modulates O-glycan
      structures on Mucin (MUC) 1 and promotes MUC1-C/beta-catenin signaling in breast
      cancer cells. These findings suggest that C1GALT1 enhances breast cancer
      malignant progression through promoting MUC1-C/beta-catenin signaling pathway.
      Unveiling the function of C1GALT1 in breast cancer opens new insights to the
      roles of C1GALT1 and O-glycosylation in tumorigenesis and renders the potential
      of C1GALT1 as a target of novel therapeutic agent development. 

PMID- 25762619
TI  - Both mTORC1 and mTORC2 are involved in the regulation of cell adhesion.
AB  - mTOR is a central controller for cell growth/proliferation and survival. Recent
      studies have shown that mTOR also regulates cell adhesion, yet the underlying
      mechanism is not known. Here we found that inhibition of mTOR by rapamycin
      reduced the basal or type I insulin-like growth factor (IGF-1)-stimulated
      adhesion of cancer cells. Further research revealed that both mTORC1 and mTORC2
      were involved in the regulation of cell adhesion, as silencing expression of
      raptor or rictor inhibited cell adhesion. Also, PP242, an mTORC1/2 kinase
      inhibitor, inhibited cell adhesion more potently than rapamycin (mTORC1
      inhibitor). Of interest, ectopic expression of constitutively active and
      rapamycin-resistant mutant of p70 kinase 1 (S6K1) or downregulation of eukaryotic
      initiation factor 4E (eIF4E)-binding protein 1 (4E-BP1) conferred resistance to
      rapamycin inhibition of cell adhesion, whereas expression of constitutively
      hypophosphorylated 4E-BP1 (4EBP1-5A) or downregulation of S6K1 suppressed cell
      adhesion. In contrast, neither genetic manipulation of Akt activity nor
      pharmacological inhibition of Akt affected cell adhesion. The results suggest
      that both mTORC1 and mTORC2 are involved in the regulation of cell adhesion; and
      mTORC1 regulates cell adhesion through S6K1 and 4E-BP1 pathways, but mTORC2
      regulates cell adhesion via Akt-independent mechanism. 

PMID- 25762621
TI  - miR-145 mediates the antiproliferative and gene regulatory effects of vitamin D3
      by directly targeting E2F3 in gastric cancer cells.
AB  - VitaminD3 signaling is involved in inhibiting the development and progression of
      gastric cancer (GC), while the active vitamin D metabolite 1-alpha,25
      dihydroxyvitamin D3 (1,25(OH)2D3)-mediated gene regulatory mechanisms in GC
      remain unclear. We found that miR-145 is induced by 1,25(OH)2D3 in a dose- and
      vitamin D receptor (VDR)-dependent manner in GC cells. Inhibition of miR-145
      reverses the antiproliferative effect of 1,25(OH)2D3. Furthermore, miR-145
      expression was lower in tumors compared with matched normal samples and
      correlated with increased the E2F3 transcription factor protein staining.
      Overexpression of miR-145 inhibited colony formation, cell viability and induced
      cell arrest in S-phase in GC cells by targeting E2F3 and CDK6. miR-145 inhibition
      consistently abrogates the 1,25(OH)2D3-mediated suppression of E2F3, CDK6, CDK2
      and CCNA2 genes. Altogether, our results indicate that miR-145 mediates the
      antiproliferative and gene regulatory effects of vitamin D3 in GC cells and might
      hold promise for prognosis and therapeutic strategies for GC treatment.

PMID- 25762622
TI  - The histidine-rich calcium binding protein (HRC) promotes tumor metastasis in
      hepatocellular carcinoma and is upregulated by SATB1.
AB  - The histidine-rich calcium binding protein (HRC) is a regulator of Ca2+
      homeostasis. Herein, we found that HRC was frequently upregulated in human
      hepatocellular carcinoma (HCC) tissues, and its expression was correlated with
      tumor size and metastasis. Moreover, HRC expression was positively related to the
      metastatic potential of HCC cell lines. Knockdown of HRC suppressed cell invasion
      and migration in vitro, whereas ectopic expression of HRC resulted in increased
      cell invasion and migration in vitro and intrahepatic and lung metastasis in
      vivo. Interestingly, the pro-invasion and pro-migration effects of HRC were
      associated with focal adhesion turnover, which was a consequence of FAK
      phosphorylation. Further experiments showed that HRC induced phospho-FAK, focal
      adhesion turnover and cell migration through Ca2+/CaM singaling. We found that
      HRC increased [Ca2+]i by inhibiting the expression of SERCA2. In addition,
      upregulation of HRC in HCC was attributed to SATB1, which is known to promote HCC
      metastasis. Ectopic expression of SATB1 enhanced HRC gene transcription by
      activating AP-1 in mainly a JNK-dependent manner. Our findings highlight HRC as a
      potential therapeutic target for HCC treatment. 

PMID- 25762623
TI  - Gluconeogenesis, lipogenesis, and HBV replication are commonly regulated by PGC
      1alpha-dependent pathway.
AB  - PGC-1alpha, a major metabolic regulator of gluconeogenesis and lipogenesis, is
      strongly induced to coactivate Hepatitis B virus (HBV) gene expression in the
      liver of fasting mice. We found that 8-Br-cAMP and glucocorticoids
      synergistically induce PGC-1alpha and its downstream targets, including PEPCK and
      G6Pase. Also, HBV core promoter activity was synergistically enhanced by 8-Br
      cAMP and glucocorticoids. Graptopetalum paraguayense (GP), a herbal medicine, is
      commonly used in Taiwan to treat liver disorders. Partially purified fraction of
      GP (named HH-F3) suppressed 8-Br-cAMP/glucocorticoid-induced G6Pase, PEPCK and
      PGC-1alpha expression and suppressed HBV core promoter activity. HH-F3 blocked
      HBV core promoter activity via inhibition of PGC-1alpha expression. Ectopically
      expressed PGC-1alpha rescued HH-F3-inhibited HBV surface antigen expression, HBV
      mRNA production, core protein levels, and HBV replication. HH-F3 also inhibited
      fatty acid synthase (FASN) expression and decreased lipid accumulation by down
      regulating PGC-1alpha. Thus, HH-F3 can inhibit HBV replication, gluconeogenesis
      and lipogenesis by down-regulating PGC-1alpha. Our study indicates that targeting
      PGC-1alpha may be a therapeutic strategy for treatment of HBV infections. HH-F3
      may have potential use for the treatment of chronic hepatitis B patients with
      associated metabolic syndrome.

PMID- 25762625
TI  - 11C-Methionine-PET: a novel and sensitive tool for monitoring of early response
      to treatment in multiple myeloma.
AB  - Multiple myeloma (MM) remains an essentially incurable hematologic malignancy.
      However, new treatment modalities and novel drugs have been introduced and thus
      additional tools for therapy monitoring are increasingly needed. Therefore, we
      evaluated the radiotracers 11C-Methionine (paraprotein-biosynthesis) and 18F-FDG
      (glucose-utilization) for monitoring response to anti-myeloma-therapy and outcome
      prediction. Influence of proteasome-inhibition on radiotracer-uptake of different
      MM cell-lines and patient-derived CD138+ plasma cells was analyzed and related to
      tumor-biology. Mice xenotransplanted with MM.1S tumors underwent MET- and FDG
      MUPET. Tumor-to-background ratios before and after 24 h, 8 and 15 days treatment
      with bortezomib were correlated to survival. Treatment reduced both MET and FDG
      uptake; changes in tracer-retention correlated with a switch from high to low
      CD138-expression. In xenotransplanted mice, MET-uptake significantly decreased by
      30-79% as early as 24 h after bortezomib injection. No significant differences
      were detected thus early with FDG. This finding was confirmed in patient-derived
      MM cells. Importantly, early reduction of MET- but not FDG-uptake correlated with
      improved survival and reduced tumor burden in mice. Our results suggest that MET
      is superior to FDG in very early assessment of response to anti-myeloma-therapy.
      Early changes in MET-uptake have predictive potential regarding response and
      survival. MET-PET holds promise to individualize therapies in MM in future. 

PMID- 25762624
TI  - The microRNA-200 family: small molecules with novel roles in cancer development,
      progression and therapy.
AB  - MicroRNAs (miRNAs) are a large family of small non-coding RNAs that negatively
      regulate protein-coding gene expression post-transcriptionally via base pairing
      between the 5' seed region of a miRNA and the 3' untranslated region (3'UTR) of a
      messenger RNA (mRNA). Recent evidence has supported the critical role that miRNAs
      play in many diseases including cancer. The miR-200 family consisting of 5
      members (miR-200a, -200b, -200c, -141, -429) is an emerging miRNA family that has
      been shown to play crucial roles in cancer initiation and metastasis, and
      potentially be important for the diagnosis and treatment of cancer. While miR
      200s were found to be critically involved in the metastatic colonization to the
      lungs in mouse mammary xenograft tumor models, a large number of studies
      demonstrated their strong suppressive effects on cell transformation, cancer cell
      proliferation, migration, invasion, tumor growth and metastasis. This review aims
      to discuss research findings about the role of the miR-200 family in cancer
      initiation, each step of cancer metastatic cascade, cancer diagnosis and
      treatment. A comprehensive summary of currently validated miR-200 targets is also
      presented. It is concluded that miR-200 family may serve as novel targets for the
      therapy of multiple types of cancer. 

PMID- 25762627
TI  - Overexpression of thymidylate synthase (TYMS) is associated with aggressive tumor
      features and early PSA recurrence in prostate cancer.
AB  - Thymidylate synthase (TYMS) plays a role in DNA synthesis and is a target for 5
      fluorouracil. In this study TYMS was analyzed by immunohistochemistry on a tissue
      microarray containing 11,152 prostate cancers. TYMS expression was higher in
      neoplastic than in normal prostate epithelium and was detectable in 72.9% of
      10,223 interpretable cancers. It was considered strong in 21.9%, moderate in
      33.4% and weak in 17.6% of tumors. TYMS overexpression was associated with
      deletions at 5q21 (p < 0.0001), 6q15 (p < 0.0001) and 3p13 (p = 0.0083) and
      gradually increased with the total number of these deletions present in the
      respective cancer sample (p < 0.0001). TYMS expression was unrelated to PTEN
      deletions (p = 0.9535) but tightly linked to high Gleason grade, advanced
      pathological tumor stage and early PSA recurrence (p < 0.0001). The prognostic
      value of TYMS was independent from the ERG status and deletions at 3p13, 5q21,
      and 6q15. In multivariate analyses the prognostic role of TYMS expression was
      independent of Gleason grade, pT stage, preoperative PSA, pN stage, or resection
      margins. TYMS expression analysis might result in clinically useful information
      in prostate cancer. The striking link to some but not all chromosomal aberrations
      might suggest a mechanistical link with specific types of DNA damage. 

PMID- 25762626
TI  - Autophagy-based survival prognosis in human colorectal carcinoma.
AB  - The role of autophagy in cancers is controversial. Here we aim to determine the
      prognostic significance of autophagy in colorectal carcinoma patients, thereby
      allowing more rational development of therapeutic strategies. Through
      transmission electron microscopy, our data first demonstrated high frequency of
      defective mitochondria was strongly associated with poor overall survival in
      colorectal carcinoma. Next immunohistochemical study showed the expressions of
      Beclin 1, LC3B and Bcl-xL in both the center of tumor and adjacent noncancerous
      mucosal region were also correlated with overall survivals. We developed an
      autophagy signature for prognosis based on these three major autophagic proteins,
      further analysis suggested it was an independent prognostic biomarker and had its
      value even within single clinical stage. Combined TNM stage and this signature
      could significantly improve the accuracy of survival prognosis. To validate these
      immunohistochemical results, an internal testing cohort and an independent
      population were also included. Our findings suggest that autophagy plays an
      important role in the clinical cancer progression. Therefore autophagic proteins
      may be valuable prognostic biomarkers in the therapy of colorectal carcinoma and
      possibly other types of cancers. 

PMID- 25762629
TI  - Extension of the in vivo half-life of endostatin and its improved anti-tumor
      activities upon fusion to a humanized antibody against tumor-associated
      glycoprotein 72 in a mouse model of human colorectal carcinoma.
AB  - Endostatin is an endogenous angiogenesis inhibitor that exhibits potential anti
      tumor efficacy in various preclinical animal models. However, its relatively
      short in vivo half-life and the long-term, frequent administration of high doses
      limit its widespread clinical use. In this study, we evaluated whether a fusion
      protein of murine endostatin (mEndo) to a humanized antibody against tumor
      associated glycoprotein 72 (TAG-72), which is highly expressed in several human
      tumor tissues including colon cancer, can extend the serum half-life and improve
      the anti-tumor efficacy of endostatin by targeted delivery to the tumor mass. The
      fusion protein (3E8-mEndo) and mEndo showed improved anti-angiogenic activity in
      vitro and in vivo, predominantly by interfering with pro-angiogenic signaling
      triggered by vascular endothelial growth factor (VEGF). Moreover, in mice treated
      with 3E8-mEndo, we observed a markedly prolonged serum half-life and
      significantly inhibited tumor growth. The improved anti-tumor activity of 3E8
      mEndo can be partially explained by increased local concentration in the tumor
      mass due to targeted delivery of 3E8-mEndo to implanted colon tumors.
      Collectively, our data clearly indicate that tumor-targeting antibody fusions to
      endostatin are a powerful strategy that improves the poor pharmacokinetic profile
      and anti-tumor efficacy of endostatin. 

PMID- 25762628
TI  - TP53 intron 1 hotspot rearrangements are specific to sporadic osteosarcoma and
      can cause Li-Fraumeni syndrome.
AB  - Somatic mutations of TP53 are among the most common in cancer and germline
      mutations of TP53 (usually missense) can cause Li-Fraumeni syndrome (LFS).
      Recently, recurrent genomic rearrangements in intron 1 of TP53 have been
      described in osteosarcoma (OS), a highly malignant neoplasm of bone belonging to
      the spectrum of LFS tumors. Using whole-genome sequencing of OS, we found
      features of TP53 intron 1 rearrangements suggesting a unique mechanism correlated
      with transcription. Screening of 288 OS and 1,090 tumors of other types revealed
      evidence for TP53 rearrangements in 46 (16%) OS, while none were detected in
      other tumor types, indicating this rearrangement to be highly specific to OS. We
      revisited a four-generation LFS family where no TP53 mutation had been identified
      and found a 445 kb inversion spanning from the TP53 intron 1 towards the
      centromere. The inversion segregated with tumors in the LFS family. Cancers in
      this family had loss of heterozygosity, retaining the rearranged allele and
      resulting in TP53 expression loss. In conclusion, intron 1 rearrangements cause
      p53-driven malignancies by both germline and somatic mechanisms and provide an
      important mechanism of TP53 inactivation in LFS, which might in part explain the
      diagnostic gap of formerly classified "TP53 wild-type" LFS.

PMID- 25762630
TI  - H89 enhances the sensitivity of cancer cells to glyceryl trinitrate through a
      purinergic receptor-dependent pathway.
AB  - High doses of the organic nitrate glyceryl trinitrate (GTN), a nitric oxide (NO)
      donor, are known to trigger apoptosis in human cancer cells. Here, we show that
      such a cytotoxic effect can be obtained with subtoxic concentrations of GTN when
      combined with H89, N-[2-(p-bromocinnamylamino)ethyl]-5
      isoquinolinesulphonamide.2HCl. This synergistic effect requires the generation of
      reactive oxygen species (ROS) from H89 and NO from GTN treatment that causes cGMP
      production and PKG activation. Furthermore, the GTN/H89 synergy was attenuated by
      inhibition of P2-purinergic receptors with suramin and competition with ATP/UDP.
      By down-regulating genes with antisense oligonucleotides, P2-purinergic receptors
      P2X3, P2Y1, and P2Y6 were found to have a role in creating this cytotoxic effect.
      Thus, H89 likely acts as an ATP mimetic synergizing with GTN to trigger apoptosis
      in aggressive cancer cells. 

PMID- 25762631
TI  - Depletion of eIF2.GTP.Met-tRNAi translation initiation complex up-regulates BRCA1
      expression in vitro and in vivo.
AB  - Most sporadic breast and ovarian cancers express low levels of the breast cancer
      susceptibility gene, BRCA1. The BRCA1 gene produces two transcripts, mRNAa and
      mRNAb. mRNAb, present in breast cancer but not in normal mammary epithelial
      cells, contains three upstream open reading frames (uORFs) in its 5'UTR and is
      translationally repressed. Comparable tandem uORFs are characteristically seen in
      mRNAs whose translational efficiency paradoxically increases when the overall
      translation rate is decreased due to phosphorylation of eukaryotic translation
      initiation factor 2 alpha (eIF2alpha). Here we show fish oil derived
      eicosopanthenoic acid (EPA) that induces eIF2alpha phosphorylation
      translationally up-regulates the expression of BRCA1 in human breast cancer
      cells. We demonstrate further that a diet rich in EPA strongly induces expression
      of BRCA1 in human breast cancer xenografts. 

PMID- 25762632
TI  - JQ1 suppresses tumor growth through downregulating LDHA in ovarian cancer.
AB  - Amplification and overexpression of c-Myc is commonly seen in human ovarian
      cancers, and this could be a potentially novel therapeutic target for this
      disease. JQ1, a selective small-molecule BET bromodomain (BRDs) inhibitor, has
      been found to suppress tumor progression in several cancer cell types. Using
      ovarian cancer cell lines, a transgenic mouse model, and primary cell cultures
      from human ovarian cancer tissues, we demonstrated that JQ1 significantly
      suppressed cellular proliferation and induced cell cycle arrest and apoptosis in
      ovarian cancer cells and mouse model via targeting c-Myc. In addition, JQ1 had
      multiple influences on cancer metabolism, particularly in the aerobic glycolysis
      pathway. JQ1 reduced both the activity and phosphorylation of LDHA, inhibited
      lactate production, and decreased the energy supply to ovarian cancer cell lines
      and tumors. Taken together, our findings suggest that JQ1 is an efficacious anti
      tumor agent in ovarian cancer that is associated with cell cycle arrest,
      induction of apoptosis and alterations of metabolism. 

PMID- 25762633
TI  - Macrophage depletion reduces postsurgical tumor recurrence and metastatic growth
      in a spontaneous murine model of melanoma.
AB  - Surgical resection of tumors is often followed by regrowth at the primary site
      and metastases may emerge rapidly following removal of the primary tumor.
      Macrophages are important drivers of tumor growth, and here we investigated their
      involvement in postoperative relapse as well as explore macrophage depletion as
      an adjuvant to surgical resection. RETAAD mice develop spontaneous metastatic
      melanoma that begins in the eye. Removal of the eyes as early as 1 week of age
      did not prevent the development of metastases; rather, surgery led to increased
      proliferation of tumor cells locally and in distant metastases. Surgery-induced
      increase in tumor cell proliferation correlated with increased macrophage density
      within the tumor. Moreover, macrophages stimulate tumor sphere formation from
      tumor cells of post-surgical but not control mice. Macrophage depletion with a
      diet containing the CSF-1R specific kinase inhibitor Ki20227 following surgery
      significantly reduced postoperative tumor recurrence and abrogated enhanced
      metastatic outgrowth. Our results confirm that tumor cells disseminate early, and
      show that macrophages contribute both to post-surgical tumor relapse and growth
      of metastases, likely through stimulating a population of tumor-initiating cells.
      Thus macrophage depletion warrants exploration as an adjuvant to surgical
      resection. 

PMID- 25762634
TI  - MiR-34a suppresses amphiregulin and tumor metastatic potential of head and neck
      squamous cell carcinoma (HNSCC).
AB  - MiR-34a is a well-known tumor metastasis inhibitor, but only a few target genes
      involved in metastasis have been identified. In HNSCC, the role of miR-34a in
      metastasis has not been fully elaborated, and the target gene of miR-34a is still
      blind. Here we addressed that, the relative lower expression of miR-34a is
      associated with HNSCC lymphatic metastasis. HNSCC metastasis was found to be
      strongly suppressed in vitro and in vivo by over-expressing miR-34a. In order to
      screen the possible target genes of miR-34a in HNSCC, a microarray-based
      differential mRNA profiling mediated by miR-34a over-expression was performed,
      and AREG was identified as a pivotal target. We demonstrated that the mRNA and
      protein levels of AREG were greatly reduced when forcing miR-34a expression. The
      correlation between AREG mRNA levels and HNSCC metastatic phenotype was also
      significant in HNSCC tissues (p < 0.01). Moreover, the results of luciferase
      assay provided the further evidence that miR-34a degraded AREG mRNA through
      targeting the 3'-UTR site. Restoration of AREG expression partially rescued miR
      34a-mediated cell invasion defects in vivo and in vitro. Additionally, Over
      expressing miR-34a greatly reduced EGFR and uPA, which were reversed by re
      expression of AREG. Taken together, these findings indicate that miR-34a targets
      AREG, and is essential in inhibition of HNSCC metastasis.

PMID- 25762635
TI  - Dual targeting of retinoid X receptor and histone deacetylase with DW22 as a
      novel antitumor approach.
AB  - Retinoid X receptor (RXR) and Histone deacetylase (HDAC) are considered important
      targets for cancer therapy due to their crucial roles in genetic or epigenetic
      regulations of cancer development and progression. Here, we evaluated the
      potential of dual targeting of RXR and HDAC using DW22 as a novel therapeutic
      approach to cancer treatment. We found that the co-expression of RXR-alpha and
      HDAC1 was frequently appeared in lung cancer and breast cancer tissues and cell
      lines. RXR was activated by DW22 in RXRalpha and HDAC1 overexpressed A549 and MDA
      MB-435 cell lines. Meanwhile, DW22 inhibited the activity of HDAC by decreasing
      its expression in A549 and MDA-MB-435 cell lines, but not in RXRalpha and HDAC1
      deficient cell lines. Moreover, DW22 suppressed cell growth, induced cell
      differentiation, prompted cell apoptosis and arrested cell cycle in A549, MDA-MB
      435 or HL60 cell lines. Treatment human umbilical vascular endothelial cells
      (HUVECs) with DW22 suppressed migration, invasion and tube formation through
      decreasing VEGF expression. The up-regulation of Ac-H3 and p21, and down
      regulation of VEGF caused by DW22 was markedly attenuated by silencing of HDAC1.
      Furthermore, knockdown of RXRalpha by siRNA completely blocked DW22-induced cell
      differentiation, but partially attenuated DW22-caused inhibition of cell
      proliferation, induction of cell apoptosis, and suppression of cell migration,
      invasion and tube formation. Moreover, intravenous administration of DW22
      significantly retarded tumor growth of A549 and MDA-MB-435 xenograft mice models,
      and induced no substantial weight loss and gross toxicity. In addition, DW22 also
      reduced cell proliferation, angiogenesis, and induced cell apoptosis in vivo.
      Collectively, our data demonstrates that dual targeting of RXR and HDAC using
      DW22 possesses pleiotropic antitumor activities both in vitro and in vivo,
      providing a novel therapeutic approach for cancer treatment. 

PMID- 25762636
TI  - A transcriptomic signature mediated by HOXA9 promotes human glioblastoma
      initiation, aggressiveness and resistance to temozolomide.
AB  - Glioblastoma is the most malignant brain tumor, exhibiting remarkable resistance
      to treatment. Here we investigated the oncogenic potential of HOXA9 in
      gliomagenesis, the molecular and cellular mechanisms by which HOXA9 renders
      glioblastoma more aggressive, and how HOXA9 affects response to chemotherapy and
      survival. The prognostic value of HOXA9 in glioblastoma patients was validated in
      two large datasets from TCGA and Rembrandt, where high HOXA9 levels were
      associated with shorter survival. Transcriptomic analyses identified novel HOXA9
      target genes with key roles in cancer-related processes, including cell
      proliferation, DNA repair, and stem cell maintenance. Functional studies with
      HOXA9-overexpressing and HOXA9-silenced glioblastoma cell models revealed that
      HOXA9 promotes cell viability, stemness and invasion, and inhibits apoptosis.
      Additionally, HOXA9 promoted the malignant transformation of human immortalized
      astrocytes in an orthotopic in vivo model, and caused tumor-associated death.
      HOXA9 also mediated resistance to temozolomide treatment in vitro and in vivo via
      upregulation of BCL2. Importantly, the pharmacological inhibition of BCL2 with
      the BH3 mimetic ABT-737 reverted temozolomide resistance in HOXA9-positive cells.
      These data establish HOXA9 as a driver of glioma initiation, aggressiveness and
      resistance to therapy. In the future, the combination of BH3 mimetics with
      temozolomide should be further explored as an alternative treatment for
      glioblastoma.

PMID- 25762637
TI  - Immunohistochemical and genomic profiles of diffuse large B-cell lymphomas:
      implications for targeted EZH2 inhibitor therapy?
AB  - Enhancer of Zeste Homolog 2 (EZH2) plays an essential epigenetic role in Diffuse
      Large B Cell Lymphoma (DLBCL) development. Recurrent somatic heterozygous gain-of
      function mutations of EZH2 have been identified in DLBCL, most notably affecting
      tyrosine 641 (Y641), inducing hyper-trimethylation of H3K27 (H3K27me3). Novel
      EZH2 inhibitors are being tested in phase 1 and 2 clinical trials but no study
      has examined which patients would most benefit from this treatment. We evaluated
      the immunohistochemical (IHC) methylation profiles of 82 patients with DLBCL, as
      well as the mutational profiles of 32 patients with DLBCL using NGS analysis of a
      panel of 34 genes involved in lymphomagenesis. A novel IHC score based on
      H3K27me2 and H3K27me3 expression was developed, capable of distinguishing
      patients with wild-type (WT) EZH2 and patients with EZH2 Y641 mutations (p = 10
      5). NGS analysis revealed a subclonal EZH2 mutation pattern in EZH2 mutant
      patients with WT-like IHC methylation profiles, while associated mutations
      capable of upregulating EZH2 were detected in WT EZH2 patients with mutant-like
      IHC methylation profiles. IHC and mutational profiles highlight in vivo hyper
      H3K27me3 and hypo-H3K27me2 status, pinpoint associated activating mutations and
      determine EZH2 mutation clonality, maximizing EZH2 inhibitor potential by
      identifying patients most likely to benefit from treatment.

PMID- 25762638
TI  - Efficacy of a Mer and Flt3 tyrosine kinase small molecule inhibitor, UNC1666, in
      acute myeloid leukemia.
AB  - Mer and Flt3 receptor tyrosine kinases have been implicated as therapeutic
      targets in acute myeloid leukemia (AML). In this manuscript we describe UNC1666,
      a novel ATP-competitive small molecule tyrosine kinase inhibitor, which potently
      diminishes Mer and Flt3 phosphorylation in AML. Treatment with UNC1666 mediated
      biochemical and functional effects in AML cell lines expressing Mer or Flt3
      internal tandem duplication (ITD), including decreased phosphorylation of Mer,
      Flt3 and downstream effectors Stat, Akt and Erk, induction of apoptosis in up to
      98% of cells, and reduction of colony formation by greater than 90%, compared to
      treatment with vehicle. These effects were dose-dependent, with inhibition of
      downstream signaling and functional effects correlating with the degree of Mer or
      Flt3 kinase inhibition. Treatment of primary AML patient samples expressing Mer
      and/or Flt3-ITD with UNC1666 also inhibited Mer and Flt3 intracellular signaling,
      induced apoptosis, and inhibited colony formation. In summary, UNC1666 is a novel
      potent small molecule tyrosine kinase inhibitor that decreases oncogenic
      signaling and myeloblast survival, thereby validating dual Mer/Flt3 inhibition as
      an attractive treatment strategy for AML. 

PMID- 25762639
TI  - AP-1-mediated chromatin looping regulates ZEB2 transcription: new insights into
      TNFalpha-induced epithelial-mesenchymal transition in triple-negative breast
      cancer.
AB  - The molecular determinants of malignant cell behaviour in triple-negative breast
      cancer (TNBC) are poorly understood. Recent studies have shown that regulators of
      epithelial-mesenchymal transition (EMT) are potential therapeutic targets for
      TNBC. In this study, we demonstrate that the inflammatory cytokine TNFalpha
      induces EMT in TNBC cells via activation of AP-1 signaling and subsequently
      induces expression of the EMT regulator ZEB2. We also show that TNFalpha
      activates both the PI3K/Akt and MAPK/ERK pathways, which act upstream of AP-1. We
      further investigated in detail AP-1 regulation of ZEB2 expression. We show that
      two ZEB2 transcripts derived from distinct promoters are both expressed in breast
      cancer cell lines and breast tumor samples. Using the chromosome conformation
      capture assay, we demonstrate that AP-1, when activated by TNFalpha, binds to a
      site in promoter 1b of the ZEB2 gene where it regulates the expression of both
      promoter 1b and 1a, the latter via mediating long range chromatin interactions.
      Overall, this work provides a plausible mechanism for inflammation-induced
      metastatic potential in TNBC, involving a novel regulatory mechanism governing
      ZEB2 isoform expression.

PMID- 25762640
TI  - Genome-wide 5-hydroxymethylcytosine modification pattern is a novel epigenetic
      feature of globozoospermia.
AB  - Discovery of 5-hydroxymethylcytosine (5hmC) in mammalian genomes has excited the
      field of epigenetics, but information on the genome-wide distribution of 5hmC is
      limited. Globozoospermia is a rare but severe cause of male infertility. To date,
      the epigenetic mechanism, especially 5hmC profiles involved in globozoospermia
      progression, remains largely unknown. Here, utilizing the chemical labeling and
      biotin-enrichment approach followed by Illumina HiSeq sequencing, we showed that
      (i) 6664, 9029 and 6318 genes contain 5hmC in normal, abnormal, and
      globozoospermia sperm, respectively; (ii) some 5hmC-containing genes
      significantly involves in spermatogenesis, sperm motility and morphology, and
      gamete generation; (iii) 5hmC is exclusively localized in sperm intron; (iv)
      approximately 40% imprinted genes have 5hmC modification in sperm genomes, but
      globozoospermia sperm exhibiting a large portion of imprinted genes lose the 5hmC
      modification; (v) six imprinted genes showed different 5hmC patterns in abnormal
      sperm (GDAP1L1, GNAS, KCNK9, LIN28B, RB1, RTL1), and five imprinted genes showed
      different 5hmC patterns in globozoospermia sperm (KCNK9, LIN28B, RB1, SLC22A18,
      ZDBF2). These results suggested that differences in genome-wide 5hmC patterns may
      in part be responsible for the sperm phenotype. All of this may improve our
      understanding of the basic molecular mechanism underlying sperm biology and the
      etiology of male infertility.

PMID- 25762641
TI  - P-selectin-mediated platelet adhesion promotes tumor growth.
AB  - Blood platelets foster carcinogenesis. We found that platelets are accumulated in
      human tumors. P-selectin deficiency and soluble P-selectin abolish platelet
      deposition within tumors, decreasing secretion of vascular endothelial growth
      factor and angiogenesis, thereby suppressing tumor growth. Binding of the P
      selectin cytoplasmic tail to talin1 triggers the talin1 N-terminal head to
      interact with the beta3 cytoplasmic tail. This activates alphaIIbbeta3 and
      recruits platelets into tumors. Platelet infiltration into solid tumors occurs
      through a P-selectin-dependent mechanism. 

PMID- 25762642
TI  - Distinct anti-oncogenic effect of various microRNAs in different mouse models of
      liver cancer.
AB  - Deregulation of microRNAs (miRNAs) is a typical feature of human hepatocellular
      carcinoma (HCC). However, the in vivo relevance of miRNAs along
      hepatocarcinogenesis remains largely unknown. Here, we show that liver tumors
      induced in mice by c-Myc overexpression or AKT/Ras co-expression exhibit distinct
      miRNA expression profiles. Among the downregulated miRNAs, eight (miR-101, miR
      107, miR-122, miR-29, miR-365, miR-375, miR-378, and miR-802) were selected and
      their tumor suppressor activity was determined by overexpressing each of them
      together with c-Myc or AKT/Ras oncogenes in mouse livers via hydrodynamic
      transfection. The tumor suppressor activity of these microRNAs was extremely
      heterogeneous in c-Myc and AKT/Ras mice: while miR-378 had no tumor suppressor
      activity, miR-107, mir-122, miR-29, miR-365 and miR-802 exhibited weak to
      moderate tumor suppressor potential. Noticeably, miR-375 showed limited
      antineoplastic activity against c-Myc driven tumorigenesis, whereas it strongly
      inhibited AKT/Ras induced hepatocarcinogenesis. Furthermore, miR-101
      significantly suppressed both c-Myc and AKT/Ras liver tumor development.
      Altogether, the present data demonstrate that different oncogenes induce distinct
      miRNA patterns, whose modulation differently affects hepatocarcinogenesis
      depending on the driving oncogenes. Finally, our findings support a strong tumor
      suppressor activity of miR-101 in liver cancer models regardless of the driver
      oncogenes involved, thus representing a promising therapeutic target in human
      HCC. 

PMID- 25762643
TI  - Snail and Slug collaborate on EMT and tumor metastasis through miR-101-mediated
      EZH2 axis in oral tongue squamous cell carcinoma.
AB  - microRNAs(miRNAs) can regulate epithelial-mesenchymal transition (EMT) through
      transcription factors, however, little is known whether EMT transcription factors
      can modulate miRNAs and further induce EMT and cancer metastasis. Here we show
      that overexpression of Snail and Slug leads to a mesenchymal phenotype and
      morphology and enhances cell invasion along with stem cell properties in squamous
      cell carcinoma of oral tongue (OTSCC) cells. Repression of miR-101 expression by
      Snail and Slug is essential for Snail/Slug-induced malignant phenotypes. The
      suppression of miR-101 subsequently activates EZH2, the sole histone
      methyltransferase, inducing EMT, migration and invasion of OTSCC cells.
      Importantly, co-overexpression of Slug and Snail correlates with poor survival
      and elevated EZH2 expression in two independent patient cohorts of OTSCC
      specimens. These findings defined a Snail and Slug/miR-101/EZH2 pathway as a
      novel regulatory axis of EMT-mediated-microRNA signaling. 

PMID- 25762644
TI  - TCGA data and patient-derived orthotopic xenografts highlight pancreatic cancer
      associated angiogenesis.
AB  - Pancreatic ductal adenocarcinomas (PDACs) overexpress pro-angiogenic factors but
      are not viewed as vascular. Using data from The Cancer Genome Atlas we
      demonstrate that a subset of PDACs exhibits a strong pro-angiogenic signature
      that includes 37 genes, such as HDAC9, that are overexpressed in PDAC arising in
      KRC mice, which express mutated Kras and lack RB. Moreover, patient-derived
      orthotopic xenografts can exhibit tumor angiogenesis, whereas conditioned media
      (CM) from KRC-derived pancreatic cancer cells (PCCs) enhance endothelial cell
      (EC) growth and migration, and activate canonical TGF-beta signaling and STAT3.
      Inhibition of the type I TGF-beta receptor with SB505124 does not alter
      endothelial activation in vitro, but decreases pro-angiogenic gene expression and
      suppresses angiogenesis in vivo. Conversely, STAT3 silencing or JAK1-2 inhibition
      with ruxolitinib blocks CM-enhanced EC proliferation. STAT3 disruption also
      suppresses endothelial HDAC9 and blocks CM-induced HDAC9 expression, whereas
      HDAC9 re-expression restores CM-enhanced endothelial proliferation. Moreover,
      ruxolitinib blocks mitogenic EC/PCC cross-talk, and suppresses endothelial p
      STAT3 and HDAC9, and PDAC progression and angiogenesis in vivo, while markedly
      prolonging survival of KRC mice. Thus, targeting JAK1-2 with ruxolitinib blocks a
      final pathway that is common to multiple pro-angiogenic factors, suppresses EC
      mediated PCC proliferation, and may be useful in PDACs with a strong pro
      angiogenic signature. 

PMID- 25762645
TI  - Tetraspanin CD9 determines invasiveness and tumorigenicity of human breast cancer
      cells.
AB  - Interaction of breast cancer cells (BCCs) with stromal components is critical for
      tumor growth and metastasis. Here, we assessed the role of CD9 in adhesion,
      migration and invasiveness of BCCs. We used co-cultures of BCCs and bone marrow
      derived multipotent mesenchymal stromal cells (MSCs), and analyzed their behavior
      and morphology by dynamic total internal reflection fluorescence, confocal and
      scanning electron microscopy. 83, 16 and 10% of contacts between MDA-MB-231
      (MDA), MA-11 or MCF-7 cells and MSCs, respectively, resulted in MSC invasion. MDA
      cells developed long magnupodia, lamellipodia and dorsal microvilli, whereas long
      microvilli emerged from MA-11 cells. MCF-7 cells displayed large dorsal ruffles.
      CD9 knockdown and antibody blockage in MDA cells inhibited MSC invasion by 95 and
      70%, respectively, suggesting that CD9 is required for this process. Remarkably,
      CD9-deficient MDA cells displayed significant alteration of their plasma
      membrane, harboring numerous peripheral and dorsal membrane ruffles instead of
      intact magnupodium/lamellipodium and microvillus, respectively. Such modification
      might explain the delayed adhesion, and hence MSC invasion. In agreement with
      this hypothesis, CD9-knockdown suppressed the metastatic capacity of MDA cells in
      mouse xenografts. Our data indicate that CD9 is implicated in BCC invasiveness
      and metastases by cellular mechanisms that involve specific CD9+ plasma membrane
      protrusions of BCCs.

PMID- 25762646
TI  - Plexin-B2 promotes invasive growth of malignant glioma.
AB  - Invasive growth is a major determinant of the high lethality of malignant
      gliomas. Plexin-B2, an axon guidance receptor important for mediating neural
      progenitor cell migration during development, is upregulated in gliomas, but its
      function therein remains poorly understood. Combining bioinformatic analyses,
      immunoblotting and immunohistochemistry of patient samples, we demonstrate that
      Plexin-B2 is consistently upregulated in all types of human gliomas and that its
      expression levels correlate with glioma grade and poor survival. Activation of
      Plexin-B2 by Sema4C ligand in glioblastoma cells induced actin-based cytoskeletal
      dynamics and invasive migration in vitro. This proinvasive effect was associated
      with activation of the cell motility mediators RhoA and Rac1. Furthermore,
      costimulation of Plexin-B2 and the receptor tyrosine kinase Met led to
      synergistic Met phosphorylation. In intracranial glioblastoma transplants, Plexin
      B2 knockdown hindered invasive growth and perivascular spreading, and resulted in
      decreased tumor vascularity. Our results demonstrate that Plexin-B2 promotes
      glioma invasion and vascularization, and they identify Plexin-B2 as a potential
      novel prognostic marker for glioma malignancy. Targeting the Plexin-B2 pathway
      may represent a novel therapeutic approach to curtail invasive growth of
      glioblastoma. 

PMID- 25762647
TI  - Removal mechanisms of dew via self-propulsion off the gecko skin.
AB  - Condensation resulting in the formation of water films or droplets is an
      unavoidable process on the cuticle or skin of many organisms. This process
      generally occurs under humid conditions when the temperature drops below the dew
      point. In this study, we have investigated dew conditions on the skin of the
      gecko Lucasium steindachneri. When condensation occurs, we show that small dew
      drops, as opposed to a thin film, form on the lizard's scales. As the droplets
      grow in size and merge, they can undergo self-propulsion off the skin and in the
      process can be carried away a sufficient distance to freely engage with external
      forces. We show that factors such as gravity, wind and fog provide mechanisms to
      remove these small droplets off the gecko skin surface. The formation of small
      droplets and subsequent removal from the skin may aid in reducing microbial
      contact (e.g. bacteria, fungi) and limit conducive growth conditions under humid
      environments. As well as providing an inhospitable microclimate for
      microorganisms, the formation and removal of small droplets may also potentially
      aid in other areas such as reduction and cleaning of some surface contaminants
      consisting of single or multiple aggregates of particles.

PMID- 25762648
TI  - Simulation of the cytoskeletal response of cells on grooved or patterned
      substrates.
AB  - We analyse the response of osteoblasts on grooved substrates via a model that
      accounts for the cooperative feedback between intracellular signalling, focal
      adhesion development and stress fibre contractility. The grooved substrate is
      modelled as a pattern of alternating strips on which the cell can adhere and
      strips on which adhesion is inhibited. The coupled modelling scheme is shown to
      capture some key experimental observations including (i) the observation that
      osteoblasts orient themselves randomly on substrates with groove pitches less
      than about 150 nm but they align themselves with the direction of the grooves on
      substrates with larger pitches and (ii) actin fibres bridge over the grooves on
      substrates with groove pitches less than about 150 nm but form a network of
      fibres aligned with the ridges, with nearly no fibres across the grooves, for
      substrates with groove pitches greater than about 300 nm. Using the model, we
      demonstrate that the degree of bridging of the stress fibres across the grooves,
      and consequently the cell orientation, is governed by the diffusion of signalling
      proteins activated at the focal adhesion sites on the ridges. For large groove
      pitches, the signalling proteins are dephosphorylated before they can reach the
      regions of the cell above the grooves and hence stress fibres cannot form in
      those parts of the cell. On the other hand, the stress fibre activation signal
      diffuses to a reasonably spatially homogeneous level on substrates with small
      groove pitches and hence stable stress fibres develop across the grooves in these
      cases. The model thus rationalizes the responsiveness of osteoblasts to the
      topography of substrates based on the complex feedback involving focal adhesion
      formation on the ridges, the triggering of signalling pathways by these adhesions
      and the activation of stress fibre networks by these signals.

PMID- 25762649
TI  - The network motif architecture of dominance hierarchies.
AB  - The widespread existence of dominance hierarchies has been a central puzzle in
      social evolution, yet we lack a framework for synthesizing the vast empirical
      data on hierarchy structure in animal groups. We applied network motif analysis
      to compare the structures of dominance networks from data published over the past
      80 years. Overall patterns of dominance relations, including some aspects of non
      interactions, were strikingly similar across disparate group types. For example,
      nearly all groups exhibited high frequencies of transitive triads, whereas cycles
      were very rare. Moreover, pass-along triads were rare, and double-dominant triads
      were common in most groups. These patterns did not vary in any systematic way
      across taxa, study settings (captive or wild) or group size. Two factors
      significantly affected network motif structure: the proportion of dyads that were
      observed to interact and the interaction rates of the top-ranked individuals.
      Thus, study design (i.e. how many interactions were observed) and the behaviour
      of key individuals in the group could explain much of the variations we see in
      social hierarchies across animals. Our findings confirm the ubiquity of dominance
      hierarchies across all animal systems, and demonstrate that network analysis
      provides new avenues for comparative analyses of social hierarchies.

PMID- 25762651
TI  - The role of distress intolerance for panic and nicotine withdrawal symptoms
      during a biological challenge.
AB  - BACKGROUND: Distress intolerance is linked to the maintenance of panic disorder
      and cigarette smoking, and may underlie both problems. METHOD: Smokers (n = 54;
      40.7% panic disorder) were recruited for an experimental study; half were
      randomly assigned to 12-hour nicotine deprivation and half smoked as usual. The
      current investigation consisted of secondary, exploratory analyses from this
      larger experimental study. Four distress intolerance indices were examined as
      predictors of anxious responding to an emotional elicitation task (10% carbon
      dioxide (CO2)-enriched air challenge); anxious responding was in turn examined as
      a predictor of post-challenge panic and nicotine withdrawal symptoms. RESULTS:
      The Distress Tolerance Scale (DTS) was significantly negatively associated with
      anxious responding to the challenge (beta = -0.41, p = 0.017). The DTS was
      negatively associated with post-challenge increases nicotine withdrawal symptoms
      indirectly through the effect of anxious responding to the challenge (b = -0.485,
      CI95% (-1.095, -0.033)). This same indirect effect was found for post-challenge
      severity of panic symptoms (b = -0.515, CI95% (-0.888, -0.208)). The DTS was
      directly predictive of post-challenge increases nicotine withdrawal symptoms, in
      the opposite direction (beta = 0.37, p = 0.009), but not panic symptom severity.
      CONCLUSIONS: Anxious responding in response to stressful experiences may explain
      the impact of perceived distress intolerance on panic and nicotine withdrawal
      symptom expression.

PMID- 25762652
TI  - Time to initial antibiotic administration, and short-term mortality among
      patients admitted with community-acquired severe infections with and without the
      presence of systemic inflammatory response syndrome: a follow-up study.
AB  - BACKGROUND: The prognosis for patients with severe infection is related to early
      treatment, including early administration of antibiotics. The study aim was to
      compare the short-term mortality among patients admitted with severe infection
      with and without systemic inflammatory response syndrome (SIRS) at arrival, and
      to ascertain whether the presence of SIRS might affect the timing of antibiotic
      administration. METHODS: In this retrospective follow-up study, we included all
      adult patients (>=15 years) presenting to a medical emergency department in the
      period between September 2010 and August 2011 with a first-time admission of
      community-acquired severe infection (infection with evidence of organ
      dysfunction), with and without SIRS at arrival. The presence of SIRS was defined
      as two or more of the criteria according to the American College of Chest
      Physicians/Society of Critical Care Medicine (ACCP/SCCM) definitions. Cases were
      identified by manual chart review using predefined criteria of infection. Data on
      vital signs, laboratory values and antibiotic treatment were obtained
      electronically. RESULTS: We included 1169 patients with infection and organ
      dysfunction, treated with antibiotics within 24 h after arrival (median age 76.1
      years (IQR 63.1-83.5), 567 (48.5%) men). In all, 886 (75.8%) presented with SIRS,
      and 283 (24.2%) presented without SIRS. Median time to antibiotics was 4.6 h (IQR
      2.9-7.0) in patients with SIRS and 6.7 h (IQR 4.5-10.3) in patients without SIRS
      (p<0.0001). Thirty-day mortality in patients with and without SIRS was 18.4% (95%
      CI 15.9% to 21.1%) and 16.6% (95% CI 12.5% to 21.5%), respectively. CONCLUSIONS:
      SIRS was absent in one-quarter of patients admitted with severe infection. The
      'door-to-antibiotics' time was significantly shorter for patients with SIRS
      compared with patients without SIRS, but no difference was found in 30-day
      mortality.

PMID- 25762650
TI  - Controlling roll perturbations in fruit flies.
AB  - Owing to aerodynamic instabilities, stable flapping flight requires ever-present
      fast corrective actions. Here, we investigate how flies control perturbations
      along their body roll angle, which is unstable and their most sensitive degree of
      freedom. We glue a magnet to each fly and apply a short magnetic pulse that rolls
      it in mid-air. Fast video shows flies correct perturbations up to 100 degrees 
      within 30 +/- 7 ms by applying a stroke-amplitude asymmetry that is well
      described by a linear proportional-integral controller. For more aggressive
      perturbations, we show evidence for nonlinear and hierarchical control
      mechanisms. Flies respond to roll perturbations within 5 ms, making this
      correction reflex one of the fastest in the animal kingdom.

PMID- 25762653
TI  - miR2GO: comparative functional analysis for microRNAs.
AB  - miR2GO is a web-based platform for comparative analyses of human miRNA functions.
      It includes two programs: miRmut2GO and miRpair2GO. miRmut2GO implements a
      knowledge-based method to assess the functional effects of genetic and somatic
      mutations in microRNA seed regions. The functional effects of a mutation are
      analysed by semantic comparison of enriched gene ontology (GO) annotations of the
      target gene sets for the wild-type and mutated alleles. miRpair2GO compares the
      functions of two different miRNAs based on the enriched functional annotations of
      their target gene sets. AVAILABILITY AND IMPLEMENTATION: The miR2GO web server is
      available at http://compbio.uthsc.edu/miR2GO.

PMID- 25762654
TI  - MIRA: mutual information-based reporter algorithm for metabolic networks.

PMID- 25762655
TI  - Comment: severe anaphylactic reaction following crotalidae polyvalent immune fab
      (ovine) administration for copperhead snakebite.

PMID- 25762656
TI  - Reply: severe anaphylactic reaction following crotalidae polyvalent immune fab
      (ovine) administration for copperhead snakebite.

PMID- 25762657
TI  - Comment: efficacy and safety of argatroban and bivalirudin in patients with
      suspected heparin-induced thrombocytopenia.

PMID- 25762658
TI  - Reply: efficacy and safety of argatroban and bivalirudin in patients with
      suspected heparin-induced thrombocytopenia.

PMID- 25762659
TI  - PKA-dependent phosphorylation of ribosomal protein S6 does not correlate with
      translation efficiency in striatonigral and striatopallidal medium-sized spiny
      neurons.
AB  - Ribosomal protein S6 (rpS6), a component of the 40S ribosomal subunit, is
      phosphorylated on several residues in response to numerous stimuli. Although
      commonly used as a marker for neuronal activity, its upstream mechanisms of
      regulation are poorly studied and its role in protein synthesis remains largely
      debated. Here, we demonstrate that the psychostimulant d-amphetamine (d-amph)
      markedly increases rpS6 phosphorylation at Ser235/236 sites in both crude and
      synaptoneurosomal preparations of the mouse striatum. This effect occurs
      selectively in D1R-expressing medium-sized spiny neurons (MSNs) and requires the
      cAMP/PKA/DARPP-32/PP-1 cascade, whereas it is independent of mTORC1/p70S6K, PKC,
      and ERK signaling. By developing a novel assay to label nascent peptidic chains,
      we show that the rpS6 phosphorylation induced in striatonigral MSNs by d-amph, as
      well as in striatopallidal MSNs by the antipsychotic haloperidol or in both
      subtypes by papaverine, is not correlated with the translation of global or 5'
      terminal oligopyrimidine tract mRNAs. Together, these results provide novel
      mechanistic insights into the in vivo regulation of the post-translational
      modification of rpS6 in the striatum and point out the lack of a relationship
      between PKA-dependent rpS6 phosphorylation and translation efficiency. 

PMID- 25762660
TI  - Persistent discharges in dentate gyrus perisoma-inhibiting interneurons require
      hyperpolarization-activated cyclic nucleotide-gated channel activation.
AB  - Parvalbumin (PV)-expressing perisoma-inhibiting interneurons (PIIs) of the
      dentate gyrus integrate rapidly correlated synaptic inputs and generate short
      duration action potentials that propagate along the axon to their output
      synapses, supporting fast inhibitory signaling onto their target cells. Here we
      show that PV-PIIs in rat and mouse dentate gyrus (DG) integrate their intrinsic
      activity over time and can turn into a persistent firing mode characterized by
      the ability to generate long-lasting trains of action potentials at ~50 Hz in the
      absence of additional inputs. Persistent firing emerges in the axons remote from
      the axon initial segment and markedly depends on hyperpolarization-activated
      cyclic nucleotide-gated channel (HCNC) activation. Persistent firing properties
      are modulated by intracellular Ca(2+) levels and somatic membrane potential.
      Detailed computational single-cell PIIs models reveal that HCNC-mediated
      conductances can contribute to persistent firing during conditions of a shift in
      their voltage activation curve to more depolarized potentials. Paired recordings
      from PIIs and their target granule cells show that persistent firing supports
      strong inhibitory output signaling. Thus, persistent firing may emerge during
      conditions of intense activation of the network, thereby providing silencing to
      the circuitry and the maintenance of sparse activity in the dentate gyrus. 

PMID- 25762662
TI  - Distribution of monocarboxylate transporters in the peripheral nervous system
      suggests putative roles in lactate shuttling and myelination.
AB  - Lactate, a product of glycolysis, has been shown to play a key role in the
      metabolic support of neurons/axons in the CNS by both astrocytes and
      oligodendrocytes through monocarboxylate transporters (MCTs). Despite such
      importance in the CNS, little is known about MCT expression and lactate function
      in the PNS. Here we show that mouse MCT1, MCT2, and MCT4 are expressed in the
      PNS. While DRG neurons express MCT1, myelinating Schwann cells (SCs) coexpress
      MCT1 and MCT4 in a domain-specific fashion, mainly in regions of noncompact
      myelin. Interestingly, SC-specific downregulation of MCT1 expression in rat
      neuron/SC cocultures led to increased myelination, while its downregulation in
      neurons resulted in a decreased amount of neurofilament. Finally, pure rat SCs
      grown in the presence of lactate exhibited an increase in the level of expression
      of the main myelin regulator gene Krox20/Egr2 and the myelin gene P0. These data
      indicate that lactate homeostasis participates in the regulation of the SC
      myelination program and reveal that similar to CNS, PNS axon-glial metabolic
      interactions are most likely mediated by MCTs. 

PMID- 25762663
TI  - Differential combinatorial coding of pheromones in two olfactory subsystems of
      the honey bee brain.
AB  - Neural coding of pheromones has been intensively studied in insects with a
      particular focus on sex pheromones. These studies favored the view that pheromone
      compounds are processed within specific antennal lobe glomeruli following a
      specialized labeled-line system. However, pheromones play crucial roles in an
      insect's life beyond sexual attraction, and some species use many different
      pheromones making such a labeled-line organization unrealistic. A combinatorial
      coding scheme, in which each component activates a set of broadly tuned units,
      appears more adapted in this case. However, this idea has not been tested
      thoroughly. We focused here on the honey bee Apis mellifera, a social insect that
      relies on a wide range of pheromones to ensure colony cohesion. Interestingly,
      the honey bee olfactory system harbors two central parallel pathways, whose
      functions remain largely unknown. Using optophysiological recordings of
      projection neurons, we compared the responses of these two pathways to 27 known
      honey bee pheromonal compounds emitted by the brood, the workers, and the queen.
      We show that while queen mandibular pheromone is processed by l-ALT (lateral
      antennal lobe tract) neurons and brood pheromone is mainly processed by m-ALT
      (median antennal lobe tract) neurons, worker pheromones induce redundant activity
      in both pathways. Moreover, all tested pheromonal compounds induce combinatorial
      activity from several AL glomeruli. These findings support the combinatorial
      coding scheme and suggest that higher-order brain centers reading out these
      combinatorial activity patterns may eventually classify olfactory signals
      according to their biological meaning. 

PMID- 25762661
TI  - Auditory properties in the parabelt regions of the superior temporal gyrus in the
      awake macaque monkey: an initial survey.
AB  - The superior temporal gyrus (STG) is on the inferior-lateral brain surface near
      the external ear. In macaques, 2/3 of the STG is occupied by an auditory cortical
      region, the "parabelt," which is part of a network of inferior temporal areas
      subserving communication and social cognition as well as object recognition and
      other functions. However, due to its location beneath the squamous temporal bone
      and temporalis muscle, the STG, like other inferior temporal regions, has been a
      challenging target for physiological studies in awake-behaving macaques. We
      designed a new procedure for implanting recording chambers to provide direct
      access to the STG, allowing us to evaluate neuronal properties and their
      topography across the full extent of the STG in awake-behaving macaques. Initial
      surveys of the STG have yielded several new findings. Unexpectedly, STG sites in
      monkeys that were listening passively responded to tones with magnitudes
      comparable to those of responses to 1/3 octave band-pass noise. Mapping results
      showed longer response latencies in more rostral sites and possible tonotopic
      patterns parallel to core and belt areas, suggesting the reversal of gradients
      between caudal and rostral parabelt areas. These results will help further
      exploration of parabelt areas. 

PMID- 25762664
TI  - Channel-mediated lactate release by K+-stimulated astrocytes.
AB  - Excitatory synaptic transmission is accompanied by a local surge in interstitial
      lactate that occurs despite adequate oxygen availability, a puzzling phenomenon
      termed aerobic glycolysis. In addition to its role as an energy substrate, recent
      studies have shown that lactate modulates neuronal excitability acting through
      various targets, including NMDA receptors and G-protein-coupled receptors
      specific for lactate, but little is known about the cellular and molecular
      mechanisms responsible for the increase in interstitial lactate. Using a panel of
      genetically encoded fluorescence nanosensors for energy metabolites, we show here
      that mouse astrocytes in culture, in cortical slices, and in vivo maintain a
      steady-state reservoir of lactate. The reservoir was released to the
      extracellular space immediately after exposure of astrocytes to a physiological
      rise in extracellular K(+) or cell depolarization. Cell-attached patch-clamp
      analysis of cultured astrocytes revealed a 37 pS lactate-permeable ion channel
      activated by cell depolarization. The channel was modulated by lactate itself,
      resulting in a positive feedback loop for lactate release. A rapid fall in
      intracellular lactate levels was also observed in cortical astrocytes of
      anesthetized mice in response to local field stimulation. The existence of an
      astrocytic lactate reservoir and its quick mobilization via an ion channel in
      response to a neuronal cue provides fresh support to lactate roles in neuronal
      fueling and in gliotransmission. 

PMID- 25762665
TI  - Impact prediction by looming visual stimuli enhances tactile detection.
AB  - From an ecological point of view, approaching objects are potentially more
      harmful than receding objects. A predator, a dominant conspecific, or a mere
      branch coming up at high speed can all be dangerous if one does not detect them
      and produce the appropriate escape behavior fast enough. And indeed, looming
      stimuli trigger stereotyped defensive responses in both monkeys and human
      infants. However, while the heteromodal somatosensory consequences of visual
      looming stimuli can be fully predicted by their spatiotemporal dynamics, few
      studies if any have explored whether visual stimuli looming toward the face
      predictively enhance heteromodal tactile sensitivity around the expected time of
      impact and at its expected location on the body. In the present study, we report
      that, in addition to triggering a defensive motor repertoire, looming stimuli
      toward the face provide the nervous system with predictive cues that enhance
      tactile sensitivity on the face. Specifically, we describe an enhancement of
      tactile processes at the expected time and location of impact of the stimulus on
      the face. We additionally show that a looming stimulus that brushes past the face
      also enhances tactile sensitivity on the nearby cheek, suggesting that the space
      close to the face is incorporated into the subjects' body schema. We propose that
      this cross-modal predictive facilitation involves multisensory convergence areas
      subserving the representation of a peripersonal space and a safety boundary of
      self. 

PMID- 25762666
TI  - Removal of perineuronal nets in the medial prefrontal cortex impairs the
      acquisition and reconsolidation of a cocaine-induced conditioned place preference
      memory.
AB  - Pyramidal neurons in the medial prefrontal cortex (mPFC) critically contribute to
      cocaine-seeking behavior in humans and rodents. Activity of these neurons is
      significantly modulated by GABAergic, parvalbumin-containing, fast-spiking
      interneurons, the majority of which are enveloped by specialized structures of
      extracellular matrix called perineuronal nets (PNNs), which are integral to the
      maintenance of many types of plasticity. Using a conditioned place preference
      (CPP) procedure, we found that removal of PNNs primarily from the prelimbic
      region of the mPFC of adult, male, Sprague Dawley rats impaired the acquisition
      and reconsolidation of a cocaine-induced CPP memory. This impairment was
      accompanied by a decrease in the number of c-Fos-positive cells surrounded by
      PNNs. Following removal of PNNs, the frequency of inhibitory currents in mPFC
      pyramidal neurons was decreased; but following cocaine-induced CPP, both
      frequency and amplitude of inhibitory currents were decreased. Our findings
      suggest that cocaine-induced plasticity is impaired by removal of prelimbic mPFC
      PNNs and that PNNs may be a therapeutic target for disruption of cocaine CPP
      memories. 

PMID- 25762668
TI  - VGluT3-expressing CCK-positive basket cells construct invaginating synapses
      enriched with endocannabinoid signaling proteins in particular cortical and
      cortex-like amygdaloid regions of mouse brains.
AB  - Invaginating synapses in the basal amygdala are a unique type of GABAergic
      synapses equipped with molecular-anatomical organization specialized for 2
      arachidonoylglycerol (2-AG)-mediated endocannabinoid signaling. Cholecystokinin
      (CCK)-positive basket cell terminals protrude into pyramidal cell somata and form
      invaginating synapses, where apposing presynaptic and postsynaptic elements are
      highly loaded with cannabinoid receptor CB1 or 2-AG synthetic enzyme
      diacylglycerol lipase-alpha (DGLalpha), respectively. The present study
      scrutinized their neurochemical and neuroanatomical phenotypes in adult mouse
      telencephalon. In the basal amygdala, vesicular glutamate transporter-3 (VGluT3)
      was transcribed in one-fourth of CB1-expressing GABAergic interneurons. The
      majority of VGluT3-positive CB1-expressing basket cell terminals apposed DGLalpha
      clusters, whereas the majority of VGluT3-negative ones did not. Importantly,
      VGluT3-positive basket cell terminals selectively constructed invaginating
      synapses. GABAA receptors accumulated on the postsynaptic membrane of
      invaginating synapses, whereas metabotropic glutamate receptor-5 (mGluR5) was
      widely distributed on the somatodendritic surface of pyramidal cells. Moreover,
      CCK2 receptor (CCK2R) was highly transcribed in pyramidal cells. In cortical
      regions, pyramidal cells equipped with such VGluT3/CB1/DGLalpha-accumulated
      invaginating synapses were found at variable frequencies depending on the
      subregions. Therefore, in addition to extreme proximity of CB1- and DGLalpha
      loaded presynaptic and postsynaptic elements, tripartite transmitter phenotype of
      GABA/glutamate/CCK is the common neurochemical feature of invaginating synapses,
      suggesting that glutamate, CCK, or both can promote 2-AG synthesis through
      activating Galphaq/11 protein-coupled mGluR5 and CCK2R. These molecular
      configurations led us to hypothesize that invaginating synapses might be evolved
      to provide some specific mechanisms of induction, regulation, and cooperativity
      for 2-AG-mediated retrograde signaling in particular cortical and cortex-like
      amygdaloid regions.

PMID- 25762667
TI  - Transmembrane AMPAR regulatory protein gamma-2 is required for the modulation of
      GABA release by presynaptic AMPARs.
AB  - Presynaptic ionotropic glutamate receptors (iGluRs) play important roles in the
      control of synaptogenesis and neurotransmitter release, yet their regulation is
      poorly understood. In particular, the contribution of transmembrane auxiliary
      proteins, which profoundly shape the trafficking and gating of somatodendritic
      iGluRs, is unknown. Here we examined the influence of transmembrane AMPAR
      regulatory proteins (TARPs) on presynaptic AMPARs in cerebellar molecular layer
      interneurons (MLIs). 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), a partial
      agonist at TARP-associated AMPARs, enhanced spontaneous GABA release in wild-type
      mice but not in stargazer mice that lack the prototypical TARP stargazin (gamma
      2). These findings were replicated in mechanically dissociated Purkinje cells
      with functional adherent synaptic boutons, demonstrating the presynaptic locus of
      modulation. In dissociated Purkinje cells from stargazer mice, AMPA was able to
      enhance mIPSC frequency, but only in the presence of the positive allosteric
      modulator cyclothiazide. Thus, ordinarily, presynaptic AMPARs are unable to
      enhance spontaneous release without gamma-2, which is required predominantly for
      its effects on channel gating. Presynaptic AMPARs are known to reduce action
      potential-driven GABA release from MLIs. Although a G-protein-dependent non
      ionotropic mechanism has been suggested to underlie this inhibition,
      paradoxically we found that gamma-2, and thus AMPAR gating, was required.
      Following glutamate spillover from climbing fibers or application of CNQX, evoked
      GABA release was reduced; in stargazer mice such effects were markedly attenuated
      in acute slices and abolished in the dissociated Purkinje cell-nerve bouton
      preparation. We suggest that gamma-2 association, by increasing charge transfer,
      allows presynaptic AMPARs to depolarize the bouton membrane sufficiently to
      modulate both phasic and spontaneous release. 

PMID- 25762669
TI  - Excitation of tuberoinfundibular dopamine neurons by oxytocin: crosstalk in the
      control of lactation.
AB  - Milk production in the nursing mother is induced by the hormone prolactin. Its
      release from the anterior pituitary is generally under tonic inhibition by
      neuroendocrine tuberoinfundibular dopamine (TIDA) neurons of the arcuate nucleus.
      Successful nursing, however, requires not only production but also ejection of
      breast milk. This function is supported by the hormone oxytocin. Here we explored
      the possibility that interaction between these functionally complementary
      hormones is mediated by TIDA neurons. First, whole-cell patch-clamp recordings
      were performed on prepubertal male rat hypothalamic slices, where TIDA neurons
      can be identified by a robust and rhythmic membrane potential oscillation.
      Oxytocin induced a switch of this rhythmic activity to tonic discharge through a
      depolarization involving direct actions on TIDA neurons. The depolarization is
      sensitive to blockade of the oxytocin receptor and is mediated by a voltage
      dependent inward current. This inward current has two components: a canonical
      transient receptor potential-like conductance in the low-voltage range, and in
      the high-voltage range, a Ca(2+)-dependent component. Finally, whole-cell and
      loose-patch recordings were also performed on slices from virgin and lactating
      female rats to evaluate the relevance of these findings for nursing. In these
      preparations, oxytocin was found to excite TIDA neurons, identified by their
      expression of tyrosine hydroxylase. These findings suggest that oxytocin can
      modulate prolactin secretion by exciting TIDA neurons, and that this may serve as
      a feedforward inhibition of prolactin release. 

PMID- 25762670
TI  - Developmental changes in hippocampal associative coding.
AB  - Behavioral analyses of the ontogeny of memory have shown that hippocampus
      dependent learning emerges relatively late in postnatal development compared with
      simple associative learning. Maturation of hippocampal mnemonic mechanisms has
      been hypothesized to underlie the development of the later emerging learning
      processes. However, the role of hippocampal maturation in learning has not been
      examined directly. The goal of the present study was to examine developmental
      changes in hippocampal neuronal coding during acquisition of a hippocampus
      dependent learning task. We recorded activity from CA1 pyramidal cells in rat
      pups while they were trained on trace eyeblink conditioning. Trace eyeblink
      conditioning is a Pavlovian conditioning task that involves the association of a
      conditioned stimulus (CS) with an unconditioned stimulus over a stimulus-free
      trace interval. The inclusion of the trace interval is what makes the task
      hippocampus dependent. In the present study, rats were trained at 21-23, 24-26,
      and 31-33 d of age. Previous research from our laboratory and others shows that
      trace conditioning begins to emerge during the third postnatal week. The results
      indicate that hippocampal neurons show a substantial increase in responsiveness
      to task-relevant events during development. Moreover, there is an age-related
      increase in the proportion of neurons that respond to a combination of trial
      events (e.g., CS and trace). Our findings indicate that the developmental
      emergence of hippocampally mediated learning is related to increases in the
      strength and complexity of CA1 associative coding. 

PMID- 25762671
TI  - Spinal cord-midbrain functional connectivity is related to perceived pain
      intensity: a combined spino-cortical FMRI study.
AB  - The dynamic interaction between ascending spinocortical nociceptive signaling and
      the descending control of the dorsal horn (DH) by brain regions such as the
      periaqueductal gray matter (PAG) plays a critical role in acute and chronic pain.
      To noninvasively investigate the processing of nociceptive stimuli in humans,
      previous fMRI studies either focused exclusively on the brain or, more recently,
      on the spinal cord. However, to relate neuronal responses in the brain to
      responses in the spinal cord and to assess the functional interplay between both
      sites in normal and aberrant conditions, fMRI of both regions within one
      experiment is necessary. Employing a new MRI acquisition protocol with two
      separate slice stacks, individually adapted resolutions and parameter settings
      that are dynamically updated to the optimized settings for the respective region
      we assessed neuronal activity in the spinal cord and in the brain within one
      measurement at 3 T. Using a parametric pain paradigm with thermal stimulation to
      the left radial forearm, we observed BOLD responses in the ipsilateral DH of the
      spinal segment C6 and corresponding neuronal responses in typical pain-processing
      brain regions. Based on correlations of adjusted time series, we are able to
      reveal functional connectivity between the spinal C6-DH and the thalamus, primary
      somatosensory cortex, bilateral insula, bilateral striatum, and key structures of
      the descending pain-modulatory system such as the PAG, the hypothalamus, and the
      amygdala. Importantly, the individual strength of the spinal-PAG coupling
      predicted individual pain ratings highlighting the functional relevance of this
      system during physiological pain signaling. 

PMID- 25762672
TI  - Neural substrates underlying the passive observation and active control of
      translational egomotion.
AB  - Moving or static obstacles often get in the way while walking in daily life.
      Avoiding obstacles involves both perceptual processing of motion information and
      controlling appropriate defensive movements. Several higher-level motion areas,
      including the ventral intraparietal area (VIP), medial superior temporal area,
      parieto-insular vestibular cortex (PIVC), areas V6 and V6A, and cingulate sulcus
      visual area, have been identified in humans by passive viewing of optic flow
      patterns that simulate egomotion and object motion. However, the roles of these
      areas in the active control of egomotion in the real world remain unclear. Here,
      we used functional magnetic resonance imaging (fMRI) to map the neural substrates
      underlying the passive observation and active control of translational egomotion
      in humans. A wide-field virtual reality environment simulated a daily scenario
      where doors randomly swing outward while walking in a hallway. The stimuli of
      door-dodging events were essentially the same in two event-related fMRI
      experiments, which compared passive and active dodges in response to swinging
      doors. Passive dodges were controlled by a computer program, while active dodges
      were controlled by the subject. Passive dodges activated several higher-level
      areas distributed across three dorsal motion streams in the temporal, parietal,
      and cingulate cortex. Active dodges most strongly activated the temporal
      vestibular stream, with peak activation located in the right PIVC. Other higher
      level motion areas including VIP showed weaker to no activation in active dodges.
      These results suggest that PIVC plays an active role in sensing and guiding
      translational egomotion that moves an observer aside from impending obstacles. 

PMID- 25762673
TI  - Dissociable cortical pathways for qualitative and quantitative mechanisms in the
      face inversion effect.
AB  - Humans' ability to recognize objects is remarkably robust across a variety of
      views unless faces are presented upside-down. Whether this face inversion effect
      (FIE) results from qualitative (distinct mechanisms) or quantitative processing
      differences (a matter of degree within common mechanisms) between upright and
      inverted faces has been intensely debated. Studies have focused on preferential
      responses to faces in face-specific brain areas, although face recognition also
      involves nonpreferential responses in non-face-specific brain areas. By using
      dynamic causal modeling with Bayesian model selection, here we show that
      dissociable cortical pathways are responsible for qualitative and quantitative
      mechanisms in the FIE in the distributed network for face recognition. When faces
      were upright, the early visual cortex (VC) and occipital and fusiform face areas
      (OFA, FFA) suppressed couplings to the lateral occipital cortex (LO), a primary
      locus of object processing. In contrast, they did not inhibit the LO when faces
      were inverted but increased couplings to the intraparietal sulcus, which has been
      associated with visual working memory. Furthermore, we found that upright and
      inverted face processing together involved the face network consisting of the VC,
      OFA, FFA, and inferior frontal gyrus. Specifically, modulatory connectivity
      within the common pathways (VC-OFA), implicated in the parts-based processing of
      faces, strongly correlated with behavioral FIE performance. The orientation
      dependent dynamic reorganization of effective connectivity indicates that the FIE
      is mediated by both qualitative and quantitative differences in upright and
      inverted face processing, helping to resolve a central debate over the mechanisms
      of the FIE. 

PMID- 25762674
TI  - Cockayne syndrome group B (Csb) and group a (Csa) deficiencies predispose to
      hearing loss and cochlear hair cell degeneration in mice.
AB  - Sensory hair cells in the cochlea, like most neuronal populations that are
      postmitotic, terminally differentiated, and non-regenerating, depend on robust
      mechanisms of self-renewal for lifelong survival. We report that hair cell
      homeostasis requires a specific sub-branch of the DNA damage nucleotide excision
      repair pathway, termed transcription-coupled repair (TCR). Cockayne syndrome
      (CS), caused by defects in TCR, is a rare DNA repair disorder with a broad
      clinical spectrum that includes sensorineural hearing loss. We tested hearing and
      analyzed the cellular integrity of the organ of Corti in two mouse models of this
      disease with mutations in the Csb gene (CSB(m/m) mice) and Csa gene (Csa(-/-)
      mice), respectively. Csb(m/m) and Csa(-/-) mice manifested progressive hearing
      loss, as measured by an increase in auditory brainstem response thresholds. In
      contrast to wild-type mice, mutant mice showed reduced or absent otoacoustic
      emissions, suggesting cochlear outer hair cell impairment. Hearing loss in
      Csb(m/m) and Csa(-/-) mice correlated with progressive hair cell loss in the base
      of the organ of Corti, starting between 6 and 13 weeks of age, which increased by
      16 weeks of age in a basal-to-apical gradient, with outer hair cells more
      severely affected than inner hair cells. Our data indicate that the hearing loss
      observed in CS patients is reproduced in mouse models of this disease. We
      hypothesize that accumulating DNA damage, secondary to the loss of TCR,
      contributes to susceptibility to hearing loss. 

PMID- 25762675
TI  - Local population synchrony and the encoding of eye position in the primate neural
      integrator.
AB  - Encoding horizontal eye position in the oculomotor system occurs through temporal
      integration of eye velocity inputs to produce tonic outputs. The nucleus
      prepositus is commonly believed to be the "neural integrator" that accomplishes
      this function through the activity of its ensemble of predominantly burst-tonic
      neurons. Single-unit characterizations and labeling studies of these neurons have
      suggested that their collective output is achieved through local feedback loops
      produced by direct connections between them. If this is the case, then the
      ensemble of burst-tonic neurons should exhibit correlated activity. To obtain
      electrophysiological evidence of local interactions between neurons, we
      simultaneously recorded pairs (n = 29) of burst-tonic neurons in the nucleus
      prepositus of rhesus macaque monkeys using eight-channel linear microelectrode
      arrays. We computed the magnitude of synchrony between their spike trains as a
      function of eye position during ocular fixations and as a function of distance
      between neurons. Importantly, we found that neurons exhibit unexpected levels of
      positive synchrony, which is maximal during contralateral fixations and weakest
      when neurons are located far apart from one another (>300 MUm). Together, our
      results support a role for shared inputs to ipsilateral pairs of burst-tonic
      neurons in the encoding of eye position in the primate nucleus prepositus. 

PMID- 25762676
TI  - kappa Opioid receptors in the nucleus accumbens shell mediate escalation of
      methamphetamine intake.
AB  - Given that the kappa opioid receptor (KOR) system has been implicated in
      psychostimulant abuse, we evaluated whether the selective KOR antagonist
      norbinaltorphimine dihydrochloride (nor-BNI) would attenuate the escalation of
      methamphetamine (METH) intake in an extended-access self-administration model.
      Systemic nor-BNI decreased the escalation of intake of long-access (LgA) but not
      short-access (ShA) self-administration. nor-BNI also decreased elevated
      progressive-ratio (PR) breakpoints in rats in the LgA condition and continued to
      decrease intake after 17 d of abstinence, demonstrating that the effects of a nor
      BNI injection are long lasting. Rats with an ShA history showed an increase in
      prodynorphin immunoreactivity in both the nucleus accumbens (NAc) core and shell,
      but LgA animals showed a selective increase in the NAc shell. Other cohorts of
      rats received nor-BNI directly into the NAc shell or core and entered into ShA or
      LgA. nor-BNI infusion in the NAc shell, but not NAc core, attenuated escalation
      of intake and PR responding for METH in LgA rats. These data indicate that the
      development and/or expression of compulsive-like responding for METH under LgA
      conditions depends on activation of the KOR system in the NAc shell and suggest
      that the dynorphin-KOR system is a central component of the neuroplasticity
      associated with negative reinforcement systems that drive the dark side of
      addiction. 

PMID- 25762677
TI  - Representation of accumulating evidence for a decision in two parietal areas.
AB  - Decisions are often made by accumulating evidence for and against the
      alternatives. The momentary evidence represented by sensory neurons is
      accumulated by downstream structures to form a decision variable, linking the
      evolving decision to the formation of a motor plan. When decisions are
      communicated by eye movements, neurons in the lateral intraparietal area (LIP)
      represent the accumulation of evidence bearing on the potential targets for
      saccades. We now show that reach-related neurons from the medial intraparietal
      area (MIP) exhibit a gradual modulation of their firing rates consistent with the
      representation of an evolving decision variable. When decisions were communicated
      by saccades instead of reaches, decision-related activity was attenuated in MIP,
      whereas LIP neurons were active while monkeys communicated decisions by saccades
      or reaches. Thus, for decisions communicated by a hand movement, a parallel flow
      of sensory information is directed to parietal areas MIP and LIP during decision
      formation. 

PMID- 25762678
TI  - Intraglomerular lateral inhibition promotes spike timing variability in principal
      neurons of the olfactory bulb.
AB  - The activity of mitral and tufted cells, the principal neurons of the olfactory
      bulb, is modulated by several classes of interneurons. Among them, diverse
      periglomerular (PG) cell types interact with the apical dendrites of mitral and
      tufted cells inside glomeruli at the first stage of olfactory processing. We used
      paired recording in olfactory bulb slices and two-photon targeted patch-clamp
      recording in vivo to characterize the properties and connections of a genetically
      identified population of PG cells expressing enhanced yellow fluorescent protein
      (EYFP) under the control of the Kv3.1 potassium channel promoter. Kv3.1-EYFP(+)
      PG cells are axonless and monoglomerular neurons that constitute ~30% of all PG
      cells and include calbindin-expressing neurons. They respond to an olfactory
      nerve stimulation with a short barrage of excitatory inputs mediated by mitral,
      tufted, and external tufted cells, and, in turn, they indiscriminately release
      GABA onto principal neurons. They are activated by even the weakest olfactory
      nerve input or by the discharge of a single principal neuron in slices and at
      each respiration cycle in anesthetized mice. They participate in a fast-onset
      intraglomerular lateral inhibition between principal neurons from the same
      glomerulus, a circuit that reduces the firing rate and promotes spike timing
      variability in mitral cells. Recordings in other PG cell subtypes suggest that
      this pathway predominates in generating glomerular inhibition. Intraglomerular
      lateral inhibition may play a key role in olfactory processing by reducing the
      similarity of principal cells discharge in response to the same incoming input. 

PMID- 25762679
TI  - Complement protein C1q modulates neurite outgrowth in vitro and spinal cord axon
      regeneration in vivo.
AB  - Traumatic injury to CNS fiber tracts is accompanied by failure of severed axons
      to regenerate and results in lifelong functional deficits. The inflammatory
      response to CNS trauma is mediated by a diverse set of cells and proteins with
      varied, overlapping, and opposing effects on histological and behavioral
      recovery. Importantly, the contribution of individual inflammatory complement
      proteins to spinal cord injury (SCI) pathology is not well understood. Although
      the presence of complement components increases after SCI in association with
      axons and myelin, it is unknown whether complement proteins affect axon growth or
      regeneration. We report a novel role for complement C1q in neurite outgrowth in
      vitro and axon regrowth after SCI. In culture, C1q increased neurite length on
      myelin. Protein and molecular assays revealed that C1q interacts directly with
      myelin associated glycoprotein (MAG) in myelin, resulting in reduced activation
      of growth inhibitory signaling in neurons. In agreement with a C1q-outgrowth
      enhancing mechanism in which C1q binding to MAG reduces MAG signaling to neurons,
      complement C1q blocked both the growth inhibitory and repulsive turning effects
      of MAG in vitro. Furthermore, C1q KO mice demonstrated increased sensory axon
      turning within the spinal cord lesion after SCI with peripheral conditioning
      injury, consistent with C1q-mediated neutralization of MAG. Finally, we present
      data that extend the role for C1q in axon growth and guidance to include the
      sprouting patterns of descending corticospinal tract axons into spinal gray
      matter after dorsal column transection SCI. 

PMID- 25762680
TI  - Time context of cue-outcome associations represented by neurons in perirhinal
      cortex.
AB  - The perirhinal cortex (PRh), which has extensive connections with diverse brain
      sites, may contribute to semantic memory by associating various types of
      information about objects. However, the extent of the types of associations in
      which PRh participates is unknown. In the present study, we let monkeys
      experience a consistent contingency between visual cues and different types of
      outcomes (water reward and sound-only acknowledgment) in a particular time
      context for many days and then recorded neuronal activities from PRh and area TE,
      which is the major source of visual inputs to PRh. We found that PRh cells
      represented the outcome type in their responses to the visual cues only in the
      time context in which the monkeys had experienced the cue-outcome contingency. In
      contrast, TE cells represented the outcome information whenever the cue appeared
      (i.e., independently from the related time context). These results showed that
      PRh cells represented not only the cue-outcome contingency but also the time
      context in which the monkeys had experienced the contingency. We conclude that
      PRh is not specific to the representation of sensory and associative properties
      of objects themselves but may represent broader information about objects,
      including the time context in which the objects are associated with particular
      outcomes. 

PMID- 25762682
TI  - Olig1 function is required for oligodendrocyte differentiation in the mouse
      brain.
AB  - Oligodendrocyte differentiation and myelination are tightly regulated processes
      orchestrated by a complex transcriptional network. Two bHLH transcription factors
      in this network, Olig1 and Olig2, are expressed exclusively by oligodendrocytes
      after late embryonic development. Although the role of Olig2 in the lineage is
      well established, the role of Olig1 is still unclear. The current studies
      analyzed the function of Olig1 in oligodendrocyte differentiation and
      developmental myelination in brain. Both oligodendrocyte progenitor cell
      commitment and oligodendrocyte differentiation were impaired in the corpus
      callosum of Olig1-null mice, resulting in hypomyelination throughout adulthood in
      the brain. As seen in previous studies with this mouse line, although there was
      an early myelination deficit in the spinal cord, essentially full recovery with
      normal spinal cord myelination was seen. Intriguingly, this regional difference
      may be partially attributed to compensatory upregulation of Olig2 protein
      expression in the spinal cord after Olig1 deletion, which is not seen in brain.
      The current study demonstrates a unique role for Olig1 in promoting
      oligodendrocyte progenitor cell commitment, differentiation, and subsequent
      myelination primarily in brain, but not spinal cord. 

PMID- 25762681
TI  - Endogenous gradients of resting potential instructively pattern embryonic neural
      tissue via Notch signaling and regulation of proliferation.
AB  - Biophysical forces play important roles throughout embryogenesis, but the roles
      of spatial differences in cellular resting potentials during large-scale brain
      morphogenesis remain unknown. Here, we implicate endogenous bioelectricity as an
      instructive factor during brain patterning in Xenopus laevis. Early frog embryos
      exhibit a characteristic hyperpolarization of cells lining the neural tube;
      disruption of this spatial gradient of the transmembrane potential (Vmem)
      diminishes or eliminates the expression of early brain markers, and causes
      anatomical mispatterning of the brain, including absent or malformed regions.
      This effect is mediated by voltage-gated calcium signaling and gap-junctional
      communication. In addition to cell-autonomous effects, we show that
      hyperpolarization of transmembrane potential (Vmem) in ventral cells outside the
      brain induces upregulation of neural cell proliferation at long range.
      Misexpression of the constitutively active form of Notch, a suppressor of neural
      induction, impairs the normal hyperpolarization pattern and neural patterning;
      forced hyperpolarization by misexpression of specific ion channels rescues brain
      defects induced by activated Notch signaling. Strikingly, hyperpolarizing
      posterior or ventral cells induces the production of ectopic neural tissue
      considerably outside the neural field. The hyperpolarization signal also
      synergizes with canonical reprogramming factors (POU and HB4), directing
      undifferentiated cells toward neural fate in vivo. These data identify a new
      functional role for bioelectric signaling in brain patterning, reveal
      interactions between Vmem and key biochemical pathways (Notch and Ca(2+)
      signaling) as the molecular mechanism by which spatial differences of Vmem
      regulate organogenesis of the vertebrate brain, and suggest voltage modulation as
      a tractable strategy for intervention in certain classes of birth defects. 

PMID- 25762683
TI  - Bidirectional regulation of eEF2 phosphorylation controls synaptic plasticity by
      decoding neuronal activity patterns.
AB  - At the sensory-motor neuron synapse of Aplysia, either spaced or continuous
      (massed) exposure to serotonin (5-HT) induces a form of intermediate-term
      facilitation (ITF) that requires new protein synthesis but not gene
      transcription. However, spaced and massed ITF use distinct molecular mechanisms
      to maintain increased synaptic strength. Synapses activated by spaced
      applications of 5-HT generate an ITF that depends on persistent protein kinase A
      (PKA) activity, whereas an ITF produced by massed 5-HT depends on persistent
      protein kinase C (PKC) activity. In this study, we demonstrate that eukaryotic
      elongation factor 2 (eEF2), which catalyzes the GTP-dependent translocation of
      the ribosome during protein synthesis, acts as a biochemical sensor that is tuned
      to the pattern of neuronal stimulation. Specifically, we find that massed
      training leads to a PKC-dependent increase in phosphorylation of eEF2, whereas
      spaced training results in a PKA-dependent decrease in phosphorylation of eEF2.
      Importantly, by using either pharmacological or dominant-negative strategies to
      inhibit eEF2 kinase (eEF2K), we were able to block massed 5-HT-dependent
      increases in eEF2 phosphorylation and subsequent PKC-dependent ITF. In contrast,
      pharmacological inhibition of eEF2K during the longer period of time required for
      spaced training was sufficient to reduce eEF2 phosphorylation and induce ITF.
      Finally, we find that the massed 5-HT-dependent increase in synaptic strength
      requires translation elongation, but not translation initiation, whereas the
      spaced 5-HT-dependent increase in synaptic strength is partially dependent on
      translation initiation. Thus, bidirectional regulation of eEF2 is critical for
      decoding distinct activity patterns at synapses by activating distinct modes of
      translation regulation. 

PMID- 25762684
TI  - Dual-channel circuit mapping reveals sensorimotor convergence in the primary
      motor cortex.
AB  - Cortical cells integrate synaptic input from multiple sources, but how these
      different inputs are distributed across individual neurons is largely unknown.
      Differences in input might account for diverse responses in neighboring neurons
      during behavior. We present a strategy for comparing the strengths of multiple
      types of input onto the same neuron. We developed methods for independent dual
      channel photostimulation of synaptic inputs using ChR2 together with ReaChR, a
      red-shifted channelrhodopsin. We used dual-channel photostimulation to probe
      convergence of sensory information in the mouse primary motor cortex. Input from
      somatosensory cortex and thalamus converges in individual neurons. Similarly,
      inputs from distinct somatotopic regions of the somatosensory cortex are
      integrated at the level of single motor cortex neurons. We next developed a
      ReaChR transgenic mouse under the control of both Flp- and Cre-recombinases that
      is an effective tool for circuit mapping. Our approach to dual-channel
      photostimulation enables quantitative comparison of the strengths of multiple
      pathways across all length scales of the brain. 

PMID- 25762685
TI  - Immune quiescence of the brain is set by astroglial connexin 43.
AB  - In the normal brain, immune cell trafficking and immune responses are strictly
      controlled and limited. This unique homeostatic equilibrium, also called brain
      immune quiescence, is crucial to maintaining proper brain functions and is
      altered in various pathological processes, from chronic immunopathological
      disorders to cognitive and psychiatric impairments. To date, the precise nature
      of factors regulating the brain/immune system interrelationship is poorly
      understood. In the present study, we demonstrate that one of these regulating
      factors is Connexin 43 (Cx43), a gap junction protein highly expressed by
      astrocytes at the blood-brain barrier (BBB) interface. We show that, by setting
      the activated state of cerebral endothelium, astroglial Cx43 controls immune
      recruitment as well as antigen presentation mechanisms in the mouse brain.
      Consequently, in the absence of astroglial Cx43, recruited immune cells elaborate
      a specific humoral autoimmune response against the von Willebrand factor A domain
      containing protein 5a, an extracellular matrix protein of the brain. Altogether,
      our results demonstrate that Cx43 is a new astroglial factor promoting the immune
      quiescence of the brain. 

PMID- 25762686
TI  - Cortical efferents lacking mutant huntingtin improve striatal neuronal activity
      and behavior in a conditional mouse model of Huntington's disease.
AB  - Abnormal electrophysiological activity in the striatum, which receives dense
      innervation from the cerebral cortex, is believed to set the stage for the
      behavioral phenotype observed in Huntington's disease (HD), a neurodegenerative
      condition caused by mutation of the huntingtin (mhtt) protein. However, cortical
      involvement is far from clear. To determine whether abnormal striatal processing
      can be explained by mhtt alone (cell-autonomous model) or by mhtt in the
      corticostriatal projection cell-cell interaction model, we used BACHD/Emx1-Cre
      (BE) mice, a conditional HD model in which full-length mhtt is genetically
      reduced in cortical output neurons, including those that project to the striatum.
      Animals were assessed beginning at 20 weeks of age for at least the next 40
      weeks, a range over which presymptomatic BACHD mice become symptomatic. Both open
      field and nest-building behavior deteriorated progressively in BACHD mice
      relative to both BE and wild-type (WT) mice. Neuronal activity patterns in the
      dorsal striatum, which receives input from the primary motor cortex (M1),
      followed a similar age progression because BACHD activity changed more rapidly
      than either BE or WT mice. However, in the M1, BE neuronal activity differed
      significantly from both WT and BACHD. Although abnormal cortical activity in BE
      mice likely reflects input from mhtt-expressing afferents, including cortical
      interneurons, improvements in BE striatal activity and behavior suggest a
      critical role for mhtt in cortical output neurons in shaping the onset and
      progression of striatal dysfunction. 

PMID- 25762687
TI  - Neural coding of sound envelope in reverberant environments.
AB  - Speech reception depends critically on temporal modulations in the amplitude
      envelope of the speech signal. Reverberation encountered in everyday environments
      can substantially attenuate these modulations. To assess the effect of
      reverberation on the neural coding of amplitude envelope, we recorded from single
      units in the inferior colliculus (IC) of unanesthetized rabbit using sinusoidally
      amplitude modulated (AM) broadband noise stimuli presented in simulated anechoic
      and reverberant environments. Although reverberation degraded both rate and
      temporal coding of AM in IC neurons, in most neurons, the degradation in temporal
      coding was smaller than the AM attenuation in the stimulus. This compensation
      could largely be accounted for by the compressive shape of the modulation input
      output function (MIOF), which describes the nonlinear transformation of
      modulation depth from acoustic stimuli into neural responses. Additionally, in a
      subset of neurons, the temporal coding of AM was better for reverberant stimuli
      than for anechoic stimuli having the same modulation depth at the ear. Using
      hybrid anechoic stimuli that selectively possess certain properties of
      reverberant sounds, we show that this reverberant advantage is not caused by
      envelope distortion, static interaural decorrelation, or spectral coloration.
      Overall, our results suggest that the auditory system may possess dual mechanisms
      that make the coding of amplitude envelope relatively robust in reverberation:
      one general mechanism operating for all stimuli with small modulation depths, and
      another mechanism dependent on very specific properties of reverberant stimuli,
      possibly the periodic fluctuations in interaural correlation at the modulation
      frequency. 

PMID- 25762689
TI  - Endoscopic Resection of Sinonasal Tract Schwannoma: Presentation, Treatment, and
      Outcome in 10 Cases.
AB  - BACKGROUND: Sinonasal schwannoma (SNS) is a rare sinonasal tract tumor whose
      presentation is similar to that of other benign nasal tumors. Very few case
      series appear in the literature. This study aims to describe the presentation,
      treatment, and outcome of 10 SNS cases from 3 referral centers. METHODS: All SNS
      cases were analyzed retrospectively. Patient demographics, tumor data, surgical
      procedures, and outcome were recorded. RESULTS: Five males and 5 females (mean
      age, 49.1 +/- 21.4 years) were included in the study. The tumor was on the left
      side in 9 patients and on the right side in 1. It originated in the middle
      turbinate in 4 cases, the ethmoid and sphenoid sinuses in 2 cases, and the nasal
      septum and infratemporal fossa in 1 case each. Tumor resection was done
      endoscopically in all cases, and there was no need for an external procedure, and
      5 patients did not require a sinusotomy. All 10 patients remained disease-free
      after a mean follow-up of 65.3 months (range, 2-120 months). CONCLUSION: Safe and
      effective endoscopic resection of SNS is feasible. If the tumor is contained
      within the nasal cavity, simple tumor excision without sinusotomy can be enough
      to resect the tumor. In more extensive disease, a wider endoscopic approach may
      be needed, but an external approach was not necessary in this series.

PMID- 25762690
TI  - Media use, cancer knowledge and lifestyle choices: a cross-sectional analysis.
AB  - BACKGROUND: Both media use and cancer knowledge have been identified as important
      predictors of a healthy lifestyle. However, little is known about the interplay
      between these two variables, and about differences between cancer diagnosed and
      non-diagnosed consumers of media and knowledge. This study investigated the
      relationship between media use (television and internet exposure) and lifestyle
      choices of cancer diagnosed and non-diagnosed individuals, and looked at the
      influence of cancer knowledge on this relationship. METHODS: A cross-sectional,
      quantitative survey (the Leuven Cancer Information Survey) was administered to
      621 cancer diagnosed and 1387 non-diagnosed individuals, aged 16-88 years old in
      Flanders (Belgium). Bivariate analyses, hierarchical linear regression analyses
      and advanced moderation and mediation analyses were conducted. RESULTS: Internet
      exposure was not a predictor of lifestyle choices. Television exposure, however,
      was a negative predictor of healthy lifestyle choices. Moreover, television
      exposure was a direct negative predictor of cancer knowledge, which in turn
      positively predicted lifestyle choices. However, no differences were found in the
      investigated relationships between the two subsamples. CONCLUSION: These results
      indicate that higher levels of television exposure coincide with less cancer
      knowledge and with less healthy lifestyle choices. It offers a pathway for
      intervention by suggesting that improving cancer knowledge through television
      might positively affect lifestyle choices.

PMID- 25762688
TI  - BDNF interacts with endocannabinoids to regulate cocaine-induced synaptic
      plasticity in mouse midbrain dopamine neurons.
AB  - Brain-derived neurotrophic factor (BDNF) and endocannabinoids (eCBs) have been
      individually implicated in behavioral effects of cocaine. The present study
      examined how BDNF-eCB interaction regulates cocaine-induced synaptic plasticity
      in the ventral tegmental area and behavioral effects. We report that BDNF and
      selective tyrosine kinase receptor B (TrkB) agonist 7,8-dihydroxyflavone (DHF)
      activated the TrkB receptor to facilitate two forms of eCB-mediated synaptic
      depression, depolarization-induced suppression of inhibition (DSI), and long-term
      depression (I-LTD) of IPSCs in ventral tegmental area dopamine neurons in mouse
      midbrain slices. The facilitation appears to be mediated by an increase in eCB
      production via phospholipase Cgamma pathway, but not by an increase in CB1
      receptor responsiveness or a decrease in eCB hydrolysis. Using Cre-loxP
      technology to specifically delete BDNF in dopamine neurons, we showed that eCB
      mediated I-LTD, cocaine-induced reduction of GABAergic inhibition, and
      potentiation of glutamatergic excitation remained intact in wild-type control
      mice, but were impaired in BDNF conditional knock-out mice. We also showed that
      cocaine-induced conditioned place preference was attenuated in BDNF conditional
      knock-out mice, in vivo pretreatments with DHF before place conditioning restored
      cocaine conditioned place preference in these mice, and the behavioral effect of
      DHF was blocked by a CB1 receptor antagonist. Together, these results suggest
      that BDNF in dopamine neurons regulates eCB responses, cocaine-induced synaptic
      plasticity, and associative learning.

PMID- 25762692
TI  - Unconscious fantasy as a special class of mental representation: a contribution
      to a model of mind.
AB  - Philosophers of mind and cognitive psychologists have proposed that "mind"
      consists of myriad mental representations, namely, conscious and unconscious
      representations of belief/desire intentions. It is argued here that unconscious
      fantasies constitute a subset of the domain of mental representations, those
      concerned with conflicting wishes, affects, and defensive maneuvers. This
      proposal anchors the unconscious fantasy construct in a model of mind that
      accords with contemporary academic views in cognitive and developmental
      psychology and philosophy of mind, thus allowing psychoanalysts to enter into
      dialogue with those disciplines. Given this formulation, unconscious fantasy
      might well serve as a theoretical construct that applies to a large group of
      theories that share certain criteria regarding mentation. An analyst would then
      be at liberty to commingle insights from a menu of different theories without
      committing metatheoretical malpractice, resulting in a principled version of
      theoretical pluralism. Published case material from Kleinian, close process
      monitoring, and self psychological perspectives demonstrates how this redefined
      unconscious fantasy construct can encompass two major types of interventions that
      analysts make: content and process interpretations. 

PMID- 25762691
TI  - Effect of stressful life events on changes in smoking among the French:
      longitudinal findings from GAZEL.
AB  - BACKGROUND: Changes in life events may play a contributing role in changes in
      smoking behaviors. The objective was to examine the impact of stressful life
      events (SLEs) on smoking among French adults. METHODS: We examined smoking
      prevalence in 20 625 employees of the French GAZEL cohort for up to 5 years
      before and after a SLE during three time periods (years -1 vs. -5; years +1 vs. 
      1; years +5 vs. +1). Repeated measures analysis of time series data indexed to
      events were used, employing generalized estimating equations. RESULTS: For women,
      comparing 1 year after vs. 1 year before SLEs, decreased odds of smoking were
      found for employment promotion (OR: 0.80; 95% CI = 0.67-0.95), marriage (OR:
      0.57; 95% CI = 0.48-0.68) and divorce (OR: 0.78; 95% CI = 0.68-0.90). Comparing 5
      years after to 1 year after SLEs, women had decreased odds of smoking for
      important purchase (OR: 0.87; 95% CI = 0.79-0.96), children leaving home (OR:
      0.83; 95% CI = 0.74-0.93), retirement (OR: 0.73; 95% CI = 0.64-0.83) and death of
      loved one (OR: 0.86; 95% CI = 0.79-0.93). For men, decreased odds of smoking were
      observed in all three time periods for all SLEs except when comparing 1 year
      before to 5 years before marriage (OR: 1.66; 95% CI = 1.09-2.52) and divorce (OR:
      1.49; 95% CI = 1.25-1.77). CONCLUSION: Time surrounding SLEs during which
      individuals are susceptible to changing smoking behaviors may be an important
      consideration.

PMID- 25762693
TI  - VX-509 (decernotinib) is a potent and selective janus kinase 3 inhibitor that
      attenuates inflammation in animal models of autoimmune disease.
AB  - Cytokines, growth factors, and other chemical messengers rely on a class of
      intracellular nonreceptor tyrosine kinases known as Janus kinases (JAKs) to
      rapidly transduce intracellular signals. A number of these cytokines are critical
      for lymphocyte development and mediating immune responses. JAK3 is of particular
      interest due to its importance in immune function and its expression, which is
      largely confined to lymphocytes, thus limiting the potential impact of JAK3
      inhibition on nonimmune physiology. The aim of this study was to evaluate the
      potency and selectivity of the investigational JAK3 inhibitor VX-509
      (decernotinib) [(R)-2-((2-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyrimidin-4-yl)amino)-2
      methyl-N-(2,2,2-trifluoroethyl)butanamide] against JAK3 kinase activity and
      inhibition of JAK3-mediated signaling in vitro and JAK3-dependent physiologic
      processes in vivo. These results demonstrate that VX-509 potently inhibits JAK3
      in enzyme assays (Ki = 2.5 nM + 0.7 nM) and cellular assays dependent on JAK3
      activity (IC50 range, 50-170 nM), with limited or no measurable potency against
      other JAK isotypes or non-JAK kinases. VX-509 also showed activity in two animal
      models of aberrant immune function. VX-509 treatment resulted in dose-dependent
      reduction in ankle swelling and paw weight and improved paw histopathology scores
      in the rat collagen-induced arthritis model. In a mouse model of oxazolone
      induced delayed-type hypersensitivity, VX-509 reduced the T cell-mediated
      inflammatory response in skin. These findings demonstrate that VX-509 is a
      selective and potent inhibitor of JAK3 in vitro and modulates proinflammatory
      response in models of immune-mediated diseases, such as collagen-induced
      arthritis and delayed-type hypersensitivity. The data support evaluation of VX
      509 for treatment of patients with autoimmune and inflammatory diseases such as
      rheumatoid arthritis. 

PMID- 25762695
TI  - Sexual dysfunction and brain tumors: why address it?

PMID- 25762694
TI  - Selective monoacylglycerol lipase inhibitors: antinociceptive versus
      cannabimimetic effects in mice.
AB  - The endogenous cannabinoid 2-arachidonoylglycerol (2-AG) plays an important role
      in a variety of physiologic processes, but its rapid breakdown by
      monoacylglycerol lipase (MAGL) results in short-lived actions. Initial MAGL
      inhibitors were limited by poor selectivity and low potency. In this study, we
      tested JZL184 [4-nitrophenyl 4-[bis(2H-1,3-benzodioxol-5
      yl)(hydroxy)methyl]piperidine-1-carboxylate] and MJN110 [2,5-dioxopyrrolidin-1-yl
      4-(bis(4-chlorophenyl)methyl)piperazine-1-carboxylate], MAGL inhibitors that
      possess increased selectivity and potency, in mouse behavioral assays of
      neuropathic pain [chronic constriction injury (CCI) of the sciatic nerve],
      interoceptive cannabimimetic effects (drug-discrimination paradigm), and
      locomotor activity in an open field test. MJN110 (1.25 and 2.5 mg/kg) and JZL184
      (16 and 40 mg/kg) significantly elevated 2-AG and decreased arachidonic acid but
      did not affect anandamide in whole brains. Both MAGL inhibitors significantly
      reduced CCI-induced mechanical allodynia with the following potencies [ED50 (95%
      confidence limit [CL]) values in mg/kg: MJN110 (0.43 [0.30-0.63]) > JZL184 (17.8
      [11.6-27.4])] and also substituted for the potent cannabinoid receptor agonist
      CP55,940 [2-[(1R,2R,5R)-5-hydroxy-2-(3-hydroxypropyl)cyclohexyl]-5-(2-methyloctan
      2-yl)phenol] in the drug-discrimination paradigm [ED50 (95% CL) values in mg/kg:
      MJN110 (0.84 [0.69-1.02]) > JZL184 (24.9 [14.6-42.5])]; however, these compounds
      elicited differential effects on locomotor behavior. Similar to cannabinoid 1
      (CB1) receptor agonists, JZL184 produced hypomotility, whereas MJN110 increased
      locomotor behavior and did not produce catalepsy or hypothermia. Although both
      drugs substituted for CP55,940 in the drug discrimination assay, MJN110 was more
      potent in reversing allodynia in the CCI model than in producing CP55,940-like
      effects. Overall, these results suggest that MAGL inhibition may alleviate
      neuropathic pain, while displaying limited cannabimimetic effects compared with
      direct CB1 receptor agonists.

PMID- 25762697
TI  - Response to "the epidemiology of glioma in adults: a 'state of the science'
      review".

PMID- 25762699
TI  - Overcoming the gender gap: increasing gender diversity, scientific scholarship
      and social legitimacy of our profession.
AB  - OBJECTIVES: This article examines a recent college review of the gender
      distribution on Royal Australian and New Zealand College of Psychiatry (RANZCP)
      committees. It includes an analysis of the key reasons we should seek to address
      the gender disparity in our committees and conference speakers and strategies by
      which to achieve this. CONCLUSIONS: The gender gap in Royal Australian and New
      Zealand College of Psychiatry leadership influences the perception, social
      legitimacy, problem-solving capacity and scientific direction of our field. We
      could improve equality in our college committees and conference speakers by
      adopting strategies used by governments and other professional associations.

PMID- 25762700
TI  - The Board evaluation: method, findings and recommendations.
AB  - OBJECTIVES: To describe the background, method, findings and recommendations of
      the Royal Australian and New Zealand College of Psychiatrists Board evaluation.
      CONCLUSIONS: An evaluation of the Board in the first half of its initial term
      indicates that the Board and the new governance processes are developing well.
      There appears to be a healthy group dynamic and effective working relationships
      with the Chief Executive Officer and management. A number of priority areas
      emerged for the Board's attention. The nature and low level of response from the
      wider membership indicate a low level of engagement in governance matters. It
      also seems that there are low levels of 'governance literacy' and that a
      different approach, perhaps facilitated focus groups, may be a more effective
      method for eliciting effective feedback on Board performance from the membership.

PMID- 25762701
TI  - Clustering of lifestyle risk behaviours among residents of forty deprived
      neighbourhoods in London: lessons for targeting public health interventions.
AB  - BACKGROUND: Clustering of lifestyle risk behaviours is very important in
      predicting premature mortality. Understanding the extent to which risk behaviours
      are clustered in deprived communities is vital to most effectively target public
      health interventions. METHODS: We examined co-occurrence and associations between
      risk behaviours (smoking, alcohol consumption, poor diet, low physical activity
      and high sedentary time) reported by adults living in deprived London
      neighbourhoods. Associations between sociodemographic characteristics and
      clustered risk behaviours were examined. Latent class analysis was used to
      identify underlying clustering of behaviours. RESULTS: Over 90% of respondents
      reported at least one risk behaviour. Reporting specific risk behaviours
      predicted reporting of further risk behaviours. Latent class analyses revealed
      four underlying classes. Membership of a maximal risk behaviour class was more
      likely for young, white males who were unable to work. CONCLUSIONS: Compared with
      recent national level analysis, there was a weaker relationship between education
      and clustering of behaviours and a very high prevalence of clustering of risk
      behaviours in those unable to work. Young, white men who report difficulty
      managing on income were at high risk of reporting multiple risk behaviours. These
      groups may be an important target for interventions to reduce premature mortality
      caused by multiple risk behaviours.

PMID- 25762705
TI  - Correction.

PMID- 25762702
TI  - 'I'm not trusted in the kitchen': food environments and food behaviours of young
      people attending school and college.
AB  - BACKGROUND: Food behaviours are important in the context of health and obesity.
      The aim was to explore the environments and food behaviours of a sample of young
      people in the North East of England to further understanding of the relationship
      between eating behaviours and environmental context. METHODS: Focus groups were
      conducted with four groups of young people aged 16-20 years (n = 40; 28 male, 12
      female) between November 2006 and June 2007. Analysis was informed by grounded
      theory methods and was an iterative process of identifying themes across the
      transcripts. RESULTS: Topics explored included: their main environment, home food
      responsibility and cooking, food outside of the home, where food was
      purchased/obtained and where food was eaten and with whom. Emergent themes
      included: the value for money in food purchases, time convenience, the car as a
      means of accessing food and health perceptions. CONCLUSIONS: The complexities of
      the food environment were illustrated. This work has highlighted the importance
      of the home food environment and parents, and indicated the importance of factors
      such as time and cost in this age group's food choices. The behavioural norms
      around food behaviours merit further exploration for this population in
      transition between adolescence and adulthood.

PMID- 25762706
TI  - Parents' Experiences of Two Different Approaches to Diabetes Care in Children
      Newly Diagnosed With Type 1 Diabetes.
AB  - Various care approaches are provided to support families with newly diagnosed
      children in their task of diabetes management. We conducted qualitative
      interviews with 36 parents of 23 children, newly diagnosed with type 1 diabetes.
      The parents were recruited from participants in a Randomized Controlled Trial
      (RCT) evaluating hospital-based care (HBC) and hospital-based home care (HBHC),
      to explore their experiences of two different approaches to diabetes care. The
      HBC was considered as being safe but not family- or diabetes-oriented. The HBHC
      was described as a relaxed environment, providing individualized accessibility
      and possibilities for situational learning and was considered as more flexible,
      promoting normality and involvement. The transition to home was followed by a
      gradual discharge, which included contradictory feelings, ambivalence, and
      hesitation and also being prepared and ready for facing daily life. The core
      category depicts differences regarding the degree of family participation, from
      passive to more active participants in initial diabetes management.

PMID- 25762707
TI  - Prognosis of non-small-cell lung cancer patients with positive pleural lavage
      cytology.
AB  - OBJECTIVES: Positive pleural lavage cytology (PLC) is considered as a precursor
      condition of pleural dissemination (PD) or malignant pleural effusion (PE), and
      one of the poor prognostic factors in surgically resected non-small-cell lung
      cancer (NSCLC) patients. Although PD and PE are classified as M1a, PLC does not
      contribute to the tumour, node and metastasis (TNM) classification of the Union
      Internationale Contre le Cancer. This study aimed to evaluate the prognostic
      effect of positive PLC status in surgically resected NSCLC patients compared with
      PD and/or PE. We also aimed to consider the contribution of positive PLC status
      to the TNM classification. METHODS: We reviewed 1572 consecutive patients with
      completely resected NSCLC, and analysed the relationship between PLC status,
      other clinicopathological factors and prognosis. The survival rates of 45
      patients with PD and/or PE were also investigated. RESULTS: Positive preresection
      PLC (pre-PLC) status was observed in 56 patients. Pre-PLC status was
      significantly associated with other clinicopathological factors. Positive pre-PLC
      patients exhibited a worse 5-year overall survival (50.6%) compared with negative
      pre-PLC patients (78.0%), but better survival than PD and/or PE patients (21.0%).
      Prognosis of positive pre-PLC patients was equal to that of pT3, negative pre-PLC
      patients; survival equality was observed when patients were stratified according
      to pN0, pN1 and pN2. CONCLUSIONS: Positive pre-PLC had the significant prognostic
      effect in surgically resected NSCLC patients. However, it is not a
      contraindication for surgical resection, unlike PD and/or PE. Our data suggest
      that positive pre-PLC should be classified as pT3 in next TNM classification.

PMID- 25762708
TI  - Tissue-engineered mitral valve: morphology and biomechanics ?.
AB  - OBJECTIVES: The present study aimed at developing tissue-engineered mitral valves
      based on cell-free ovine mitral allografts. METHODS: The ovine mitral valves
      (OMVs) (n = 46) were harvested in the local slaughter house. They were
      decellularized using detergent solutions and DNase. The effectiveness of
      decellularization was assessed by histological (haematoxylin-eosin, Movat's
      pentachrome) and immunofluorescent staining (for DNA and alpha-Gal), and DNA
      quantification. To reveal the receptiveness of decellularized tissue to
      endothelial cells (ECs), the valve leaflets were reseeded with ovine ECs, derived
      from endothelial progenitor cells in vitro. For assessment of biomechanical
      properties, uniaxial tensile tests were carried out. RESULTS: Histology and
      immunofluorescent staining revealed absence of cell nuclei in decellularized
      leaflets, chordae and papillary muscles. According to the software for
      immunofluorescence analysis, reduction in DNA and alpha-Gal was 99.9 and 99.6%,
      respectively. DNA-quantification showed 71.2% reduction in DNA content without
      DNase and 96.4% reduction after DNase treatment. Decellularized leaflets were
      comparable with native in ultimate tensile strain (native, 0.34 +/- 0.09 mm/mm,
      vs decellularized, 0.44 +/- 0.1 mm/mm; P = 0.09), and elastin modulus (native,
      0.39 +/- 0.27, vs decellularized, 0.57 +/- 0.55, P = 0.46), had increased
      ultimate tensile stress (native, 1.23 +/- 0.35 MPa, vs decellularized 2.12 +/-
      0.43 MPa; P = 0.001) and collagen modulus (native, 5.5 +/- 1.26, vs
      decellularized, 8.29 +/- 2.9; P = 0.04). After EC seeding, immunofluorescent
      staining revealed a monolayer of CD31-, eNOS- and vWF-positive cells on the
      surface of the leaflet, as well as a typical cobble-stone morphology of those
      cells. CONCLUSIONS: Decellularization of ovine mitral valve results in a mitral
      valves scaffold with mechanical properties comparable with native tissue, and a
      graft surface, which can be repopulated by endothelial cells.

PMID- 25762709
TI  - Clinical prodromes of neurodegeneration in Anderson-Fabry disease.
AB  - OBJECTIVE: To estimate the prevalence of prodromal clinical features of
      neurodegeneration in patients with Anderson-Fabry disease (AFD) in comparison to
      age-matched controls. METHODS: This is a single-center, prospective, cross
      sectional study in 167 participants (60 heterozygous females and 50 hemizygous
      males with genetically confirmed AFD, 57 age-matched controls) using a clinical
      screening program consisting of structured interview, quantitative tests of motor
      function, and assessments of cognition, depression, olfaction, orthostatic
      intolerance, pain, REM sleep behavior disorder, and daytime sleepiness. RESULTS:
      In comparison to age-matched controls (mean age 48.3 years), patients with AFD
      (mean age 49.0 years) showed slower gait and transfer speed, poorer fine manual
      dexterity, and lower hand speed, which was independent of focal symptoms due to
      cerebrovascular disease. Patients with AFD were more severely affected by
      depression, pain, and daytime sleepiness and had a lower quality of life. These
      motor and nonmotor manifestations significantly correlated with clinical disease
      severity. However, patients with AFD did not reveal extrapyramidal motor features
      or signs of significant cognitive impairment, hyposmia, orthostatic intolerance,
      or REM sleep behavior disorder, which commonly precede later neurodegenerative
      disease. In our cohort, there were no differences in neurologic manifestations of
      AFD between heterozygous females and hemizygous males. CONCLUSIONS: Aside from
      cerebrovascular manifestations and small fiber neuropathy, AFD results in a
      distinct neurologic phenotype comprising poorer motor performance and specific
      nonmotor features. In contrast to functional loss of glucocerebrosidase in
      Gaucher disease, alpha-galactosidase deficiency in AFD is not associated with a
      typical cluster of clinical features prodromal for neurodegenerative diseases,
      such as Parkinson disease.

PMID- 25762711
TI  - Physical activity, white matter hyperintensities, and motor function: bringing
      out the reserves.

PMID- 25762710
TI  - Physical activity, motor function, and white matter hyperintensity burden in
      healthy older adults.
AB  - OBJECTIVE: To test the hypothesis that physical activity modifies the association
      between white matter hyperintensity (WMH) burden and motor function in healthy
      older persons without dementia. METHODS: Total daily activity (exercise and
      nonexercise physical activity) was measured for up to 11 days with actigraphy
      (Actical; Philips Respironics, Bend, OR) in 167 older adults without dementia
      participating in the Rush Memory and Aging Project. Eleven motor performances
      were summarized into a previously described global motor score. WMH volume was
      expressed as percent of intracranial volume. Linear regression models, adjusted
      for age, education, and sex, were performed with total WMH volume as the
      predictor and global motor score as the outcome. Terms for total daily physical
      activity and its interaction with WMH volume were then added to the model.
      RESULTS: Higher WMH burden was associated with lower motor function (p = 0.006),
      and total daily activity was positively associated with motor function (p =
      0.002). Total daily activity modified the association between WMH and motor
      function (p = 0.007). WMH burden was not associated with motor function in
      persons with high activity (90th percentile). By contrast, higher WMH burden
      remained associated with lower motor function in persons with average (50th
      percentile; estimate = -0.304, slope = -0.133) and low (10th percentile; estimate
      = -1.793, slope = -0.241) activity. CONCLUSIONS: Higher levels of physical
      activity may reduce the effect of WMH burden on motor function in healthy older
      adults.

PMID- 25762712
TI  - Hematopoietic mobilization: Potential biomarker of response to natalizumab in
      multiple sclerosis.
AB  - OBJECTIVE: To ascertain the mobilization from the bone marrow and the functional
      relevance of the increased number of circulating hematopoietic stem and
      progenitor cells (HSPC) induced by the anti-alpha-4 integrin antibody natalizumab
      in patients with multiple sclerosis (MS). METHODS: We evaluated CD45(low)CD34+
      HSPC frequency by flow cytometry in blood from 45 natalizumab-treated patients
      (12 of whom were prospectively followed during the first year of treatment as
      part of a pilot cohort and 16 prospectively followed for validation), 10
      untreated patients with MS, and 24 healthy donors. In the natalizumab-treated
      group, we also assessed sorted HSPC cell cycle status, T- and B-lymphocyte
      subpopulation frequencies (n = 29), and HSPC differentiation potential (n = 10).
      RESULTS: Natalizumab-induced circulating HSPC were predominantly quiescent,
      suggesting recent mobilization from the bone marrow, and were capable of
      differentiating ex vivo. Circulating HSPC numbers were significantly increased
      during natalizumab, but heterogeneously, allowing the stratification of mobilizer
      and nonmobilizer subgroups. Nonmobilizer status was associated with persistence
      of disease activity during treatment. The frequency of B cells and CD103+CD8+
      regulatory T cells persistently increased, more significantly in mobilizer
      patients, who also showed a specific naive/memory B-cell profile. CONCLUSIONS:
      The data suggest that natalizumab-induced circulating HSPC increase is the result
      of true mobilization from the bone marrow and has clinical and immunologic
      relevance. HSPC mobilization, associated with clinical remission and increased
      proportion of circulating B and regulatory T cells, may contribute to the
      treatment's mode of action; thus, HSPC blood counts could represent an early
      biomarker of responsiveness to natalizumab.

PMID- 25762713
TI  - Ethics of genetic and biomarker test disclosures in neurodegenerative disease
      prevention trials.
AB  - OBJECTIVE: Prevention trials for neurodegenerative diseases use genetic or other
      risk marker tests to select participants but there is concern that this could
      involve coercive disclosure of unwanted information. This has led some trials to
      use blinded enrollment (participants are tested but not told of their risk marker
      status). We examined the ethics of blinded vs transparent enrollment using well
      established criteria for assessing the ethics of clinical research. METHODS:
      Normative analysis applying 4 key ethical criteria-favorable risk-benefit ratio,
      informed consent, fair subject selection, and scientific validity-to blinded vs
      transparent enrollment, using current evidence and state of Alzheimer disease
      (AD) and other prevention trials. RESULTS: Current evidence on the psychosocial
      impact of risk marker disclosure and considerations of scientific benefit do not
      support an obligation to use blinded enrollment in prevention trials. Nor does
      transparent enrollment coerce or involve undue influence of potential
      participants. Transparent enrollment does not unfairly exploit vulnerable
      participants or limit generalizability of scientific findings of prevention
      trials. However, if the preferences of a community of potential participants
      would affect the rigor or feasibility of a prevention trial using transparent
      enrollment, then investigators are required by considerations of scientific
      validity to use blinded enrollment. CONCLUSIONS: Considerations of risks and
      benefits, informed consent, and fair subject selection do not require the use of
      blinded enrollment for AD prevention trials. Blinded enrollment in AD prevention
      trials may sometimes be necessary because of the need for scientific validity,
      not because it prevents coercion or undue influence.

PMID- 25762714
TI  - Differential patterns of spinal cord and brain atrophy in NMO and MS.
AB  - OBJECTIVE: To investigate spinal cord and brain atrophy in neuromyelitis optica
      (NMO), and its relationship with other MRI measurements and clinical disability,
      compared with patients with multiple sclerosis (MS) and healthy controls (HC).
      METHODS: We recruited 35 patients with NMO, 35 patients with MS, and 35 HC, who
      underwent both spinal cord and brain MRI. Mean upper cervical cord area (MUCCA),
      brain parenchymal fraction (BPF), gray matter fraction (GMF), white matter
      fraction (WMF), and spinal cord and brain lesion loads were measured and compared
      among groups. Multivariate associations between MUCCA and brain volume
      measurement and clinical variables were assessed by partial correlations and
      multiple linear regression. RESULTS: Patients with NMO showed smaller MUCCA than
      HC (p = 0.004), and patients with MS had a trend of smaller MUCCA compared to HC
      (p = 0.07), with no significant difference between the patient groups. Patients
      with NMO showed lower BPF than HC, and patients with MS had lower BPF and GMF
      than patients with NMO. In NMO, MUCCA was correlated with Expanded Disability
      Status Scale score (EDSS), number of relapses, and total spinal cord lesion
      length, while in MS, MUCCA was correlated with WMF and EDSS. MUCCA was the only
      independent variable for predicting clinical disability measured by EDSS in NMO
      (R(2) = 0.55, p < 0.001) and MS (R(2) = 0.17, p = 0.013). CONCLUSION: NMO showed
      predominately spinal cord atrophy with mild brain atrophy, while MS demonstrated
      more brain atrophy, especially in the gray matter. MUCCA is the main MRI-derived
      parameter for explaining clinical disability in NMO and MS, and may serve as a
      potential biomarker for further clinical trials, especially in NMO.

PMID- 25762716
TI  - Transapical implantation of a new second-generation transcatheter heart valve in
      patients with pure aortic regurgitation: a preliminary report.
AB  - Transcatheter aortic valve implantation (TAVI) has become an effective treatment
      option for high-risk or inoperable patients with aortic stenosis. However,
      experience with TAVI for non-calcified aortic regurgitation is still limited. The
      new J-Valve(TM) system is a new second-generation TAVI device that is designed
      for transapical implantation. It is characterized by three U-shaped, anatomically
      oriented devices-'graspers' that could facilitate intuitive 'self-positioning'
      valve implantation and provide extra-radial fixation by embracing the native
      valve leaflets. Here, we reported the initial experience of TAVI in high-risk
      patients with pure aortic regurgitation using the J-Valve(TM) system.

PMID- 25762715
TI  - Association of hospitalization with long-term cognitive and brain MRI changes in
      the ARIC cohort.
AB  - OBJECTIVE: To determine whether hospitalization is associated with subsequent
      cognitive decline or changes on brain MRI in a community-based cohort. METHODS:
      Baseline and follow-up cognitive testing (n = 2,386) and MRI scans with
      standardized assessments (n = 885) were available from a subset of white and
      black participants in the Atherosclerosis Risk in Communities study. Cognitive
      tests included the Delayed Word Recall Test (DWRT), Digit Symbol Substitution
      Test (DSST), and Word Fluency Test (WFT). Hospitalization characteristics were
      determined using ICD-9 codes. Regression models adjusted for demographics,
      education, comorbidities, and APOE epsilon4 were used to estimate the independent
      association of hospitalization with changes in cognition or neuroimaging.
      RESULTS: Over a mean 14.1 years between visits, 1,266 participants (53.1%) were
      hospitalized. Hospitalization compared with no hospitalization was associated
      with greater decline in DSST scores (1.25 points greater decline, p < 0.001) but
      no difference in DWRT or WFT score change. Each additional hospitalization, as
      well as a critical illness vs noncritical illness hospitalization, was associated
      with greater decline in DSST scores. A subset of participants (n = 885) underwent
      MRI scans separated by 10.5 years. Hospitalization (n = 392) compared with no
      hospitalization was associated with a 57% higher odds of increasing ventricular
      size at follow-up. Each additional hospitalization, as well as having a critical
      illness vs noncritical illness hospitalization, and having a hospitalization with
      major surgery vs no surgery was associated with greater odds of increased
      ventricular size. CONCLUSIONS: Cognitive decline and neuroimaging changes may
      occur after hospitalization, independent of baseline demographics and
      comorbidities.

PMID- 25762717
TI  - The Class I-Specific HDAC Inhibitor MS-275 Decreases Motivation to Consume
      Alcohol and Relapse in Heavy Drinking Rats.
AB  - BACKGROUND: New strategies for the treatment of alcohol dependence are a pressing
      need, and recent evidence suggests that targeting enzymes involved in epigenetic
      mechanisms seems to have great potential. Among these mechanisms, alteration of
      histone acetylation by histone deacetylases is of great importance for gene
      expression and has also been implicated in addiction. Here, we examined whether
      intra-cerebroventricular administration of MS-275, a class I-specific histone
      deacetylase inhibitor, could alter ethanol self-administration, motivation to
      consume ethanol, and relapse in heavy drinking rats. METHODS: Male Long Evans
      rats trained to self-administer high levels of ethanol received intra
      cerebroventricular micro-infusions of MS-275 (250 uM, 500 uM, and 1000 uM) 3
      hours prior to the self-administration sessions. RESULTS: First, we demonstrated
      that intra-cerebroventricular infusion of MS-275 increases acetylation of Histone
      4 within the nucleus accumbens nucleus accumbens and the dorsolateral striatum.
      Second, we observed that MS-275 decreases ethanol self-administration by about
      75%. We found that 2 consecutive daily injections are necessary to decrease
      ethanol self-administration. Additionally, the dose-response curve test indicated
      that MS-275 has a U-shape effect on ethanol self-administration with the dose of
      500 uM as the most efficient dose. Furthermore, we showed that MS-275 also
      diminished the motivation to consume ethanol (25% decrease), and finally, we
      demonstrated that MS-275 reduced relapse (by about 50%) and postponed
      reacquisition even when the treatment was stopped. CONCLUSIONS: Our study
      confirms the potential therapeutic interest of targeting epigenetic mechanisms in
      excessive alcohol drinking and strengthens the interest of focusing on specific
      isoforms of histone deacetylases.

PMID- 25762718
TI  - Hippocampal-Dependent Antidepressant Action of the H3 Receptor Antagonist
      Clobenpropit in a Rat Model of Depression.
AB  - BACKGROUND: Histamine is a modulatory neurotransmitter regulating neuronal
      activity. Antidepressant drugs target modulatory neurotransmitters, thus
      ultimately regulating glutamatergic transmission and plasticity. Histamine H3
      receptor (H3R) antagonists have both pro-cognitive and antidepressant effects;
      however, the mechanism by which they modulate glutamate transmission is not
      clear. We measured the effects of the H3R antagonist clobenpropit in the Flinders
      Sensitive Line (FSL), a rat model of depression with impaired memory and altered
      glutamatergic transmission. METHODS: Behavioral tests included the forced swim
      test, memory tasks (passive avoidance, novel object recognition tests), and
      anxiety-related paradigms (novelty suppressed feeding, social interaction,
      light/dark box tests). Hippocampal protein levels were detected by Western blot.
      Hippocampal plasticity was studied by in slice field recording of CA3-CA1 long
      term synaptic potentiation (LTP), and glutamatergic transmission by whole-cell
      patch clamp recording of excitatory postsynaptic currents (EPSCs) in CA1
      pyramidal neurons. RESULTS: Clobenpropit, administered systemically or directly
      into the hippocampus, decreased immobility during the forced swim test; systemic
      injections reversed memory deficits and increased hippocampal GluN2A protein
      levels. FSL rats displayed anxiety-related behaviors not affected by clobenpropit
      treatment. Clobenpropit enhanced hippocampal plasticity, but did not affect
      EPSCs. H1R and H2R antagonists prevented the clobenpropit-induced increase in LTP
      and, injected locally into the hippocampus, blocked clobenpropit's effect in the
      forced swim test. CONCLUSIONS: Clobenpropit's antidepressant effects and the
      enhanced synaptic plasticity require hippocampal H1R and H2R activation,
      suggesting that clobenpropit acts through disinhibition of histamine release.
      Clobenpropit reverses memory deficits and increases hippocampal GluN2A expression
      without modifying anxiety-related phenotypes or EPSCs in CA1 pyramidal neurons.

PMID- 25762719
TI  - Tyrosine Kinase 2-mediated Signal Transduction in T Lymphocytes Is Blocked by
      Pharmacological Stabilization of Its Pseudokinase Domain.
AB  - Inhibition of signal transduction downstream of the IL-23 receptor represents an
      intriguing approach to the treatment of autoimmunity. Using a chemogenomics
      approach marrying kinome-wide inhibitory profiles of a compound library with the
      cellular activity against an IL-23-stimulated transcriptional response in T
      lymphocytes, a class of inhibitors was identified that bind to and stabilize the
      pseudokinase domain of the Janus kinase tyrosine kinase 2 (Tyk2), resulting in
      blockade of receptor-mediated activation of the adjacent catalytic domain. These
      Tyk2 pseudokinase domain stabilizers were also shown to inhibit Tyk2-dependent
      signaling through the Type I interferon receptor but not Tyk2-independent
      signaling and transcriptional cellular assays, including stimulation through the
      receptors for IL-2 (JAK1- and JAK3-dependent) and thrombopoietin (JAK2
      dependent), demonstrating the high functional selectivity of this approach. A
      crystal structure of the pseudokinase domain liganded with a representative
      example showed the compound bound to a site analogous to the ATP-binding site in
      catalytic kinases with features consistent with high ligand selectivity. The
      results support a model where the pseudokinase domain regulates activation of the
      catalytic domain by forming receptor-regulated inhibitory interactions. Tyk2
      pseudokinase stabilizers, therefore, represent a novel approach to the design of
      potent and selective agents for the treatment of autoimmunity. 

PMID- 25762720
TI  - Phosphorylation of Sae2 Mediates Forkhead-associated (FHA) Domain-specific
      Interaction and Regulates Its DNA Repair Function.
AB  - Saccharomyces cerevisiae Sae2 and its ortholog CtIP in higher eukaryotes have a
      conserved role in the initial processing of DNA lesions and influencing their
      subsequent repair pathways. Sae2 is phosphorylated by the ATR/ATM family kinases
      Mec1 and Tel1 in response to DNA damage. Among the Mec1/Tel1 consensus
      phosphorylation sites of Sae2, we found that mutations of Thr-90 and Thr-279 of
      Sae2 into alanine caused a persistent Rad53 activation in response to a transient
      DNA damage, similar to the loss of Sae2. To gain insight into the function of
      this phosphorylation of Sae2, we performed a quantitative proteomics analysis to
      identify its associated proteins. We found that phosphorylation of Thr-90 of Sae2
      mediates its interaction with Rad53, Dun1, Xrs2, Dma1, and Dma2, whereas Rad53
      and Dun1 additionally interact with phosphorylated Thr-279 of Sae2. Mutations of
      the ligand-binding residues of Forkhead-associated (FHA) domains of Rad53, Dun1,
      Xrs2, Dma1, and Dma2 abolished their interactions with Sae2, revealing the
      involvement of FHA-specific interactions. Mutations of Thr-90 and Thr-279 of Sae2
      caused a synergistic defect when combined with sgs1Delta and exo1Delta and
      elevated gross chromosomal rearrangements. Likewise, mutations of RAD53 and DUN1
      caused a synthetic growth defect with sgs1Delta and elevated gross chromosomal
      rearrangements. These findings suggest that threonine-specific phosphorylation of
      Sae2 by Mec1 and Tel1 contributes to DNA repair and genome maintenance via its
      interactions with Rad53 and Dun1. 

PMID- 25762721
TI  - Phosphodiesterase 10A Is Tethered to a Synaptic Signaling Complex in Striatum.
AB  - Phosphodiesterase 10A (PDE10A) is a dual substrate PDE that can hydrolyze both
      cGMP and cAMP. In brain, PDE10A is almost exclusively expressed in the striatum.
      In several studies, PDE10A has been implicated in regulation of striatal output
      using either specific inhibitors or PDE10A knock-out mice and has been suggested
      as a promising target for novel antipsychotic drugs. In striatal medium spiny
      neurons, PDE10A is localized at the plasma membrane and in dendritic spines close
      to postsynaptic densities. In the present study, we identify PDE10A as the major
      cAMP PDE in mouse striatum and monitor PKA-dependent PDE10A phosphorylation. With
      recombinantly expressed PDE10A we demonstrate that phosphorylation does not alter
      PDE10A activity. In striatum, PDE10A was found to be associated with the A kinase
      anchoring protein AKAP150 suggesting the existence of a multiprotein signaling
      complex localizing PDE10A to a specific functional context at synaptic membranes.
      Furthermore, the cAMP effector PKA, the NMDA receptor subunits NR2A and -B, as
      well as PSD95, were tethered to the complex. In agreement, PDE10A was almost
      exclusively found in multiprotein complexes as indicated by migration in high
      molecular weight fractions in size exclusion chromatography. Finally, affinity of
      PDE10A to the signaling complexes formed around AKAP150 was reduced by PDE10A
      phosphorylation. The data indicate that phosphorylation of PDE10 has an impact on
      the interaction with other signaling proteins and adds an additional line of
      complexity to the role of PDE10 in regulation of synaptic transmission. 

PMID- 25762722
TI  - Group VIA Phospholipase A2 (iPLA2beta) Modulates Bcl-x 5'-Splice Site Selection
      and Suppresses Anti-apoptotic Bcl-x(L) in beta-Cells.
AB  - Diabetes is a consequence of reduced beta-cell function and mass, due to beta
      cell apoptosis. Endoplasmic reticulum (ER) stress is induced during beta-cell
      apoptosis due to various stimuli, and our work indicates that group VIA
      phospholipase A2beta (iPLA2beta) participates in this process. Delineation of
      underlying mechanism(s) reveals that ER stress reduces the anti-apoptotic Bcl
      x(L) protein in INS-1 cells. The Bcl-x pre-mRNA undergoes alternative pre-mRNA
      splicing to generate Bcl-x(L) or Bcl-x(S) mature mRNA. We show that both
      thapsigargin-induced and spontaneous ER stress are associated with reductions in
      the ratio of Bcl-x(L)/Bcl-x(S) mRNA in INS-1 and islet beta-cells. However,
      chemical inactivation or knockdown of iPLA2beta augments the Bcl-x(L)/Bcl-x(S)
      ratio. Furthermore, the ratio is lower in islets from islet-specific RIP
      iPLA2beta transgenic mice, whereas islets from global iPLA2beta(-/-) mice exhibit
      the opposite phenotype. In view of our earlier reports that iPLA2beta induces
      ceramide accumulation through neutral sphingomyelinase 2 and that ceramides shift
      the Bcl-x 5'-splice site (5'SS) selection in favor of Bcl-x(S), we investigated
      the potential link between Bcl-x splicing and the iPLA2beta/ceramide axis.
      Exogenous C6-ceramide did not alter Bcl-x 5'SS selection in INS-1 cells, and
      neutral sphingomyelinase 2 inactivation only partially prevented the ER stress
      induced shift in Bcl-x splicing. In contrast, 5(S)-hydroxytetraenoic acid
      augmented the ratio of Bcl-x(L)/Bcl-x(S) by 15.5-fold. Taken together, these data
      indicate that beta-cell apoptosis is, in part, attributable to the modulation of
      5'SS selection in the Bcl-x pre-mRNA by bioactive lipids modulated by iPLA2beta. 

PMID- 25762723
TI  - Compartmentalized accumulation of cAMP near complexes of multidrug resistance
      protein 4 (MRP4) and cystic fibrosis transmembrane conductance regulator (CFTR)
      contributes to drug-induced diarrhea.
AB  - Diarrhea is one of the most common adverse side effects observed in ~7% of
      individuals consuming Food and Drug Administration (FDA)-approved drugs. The
      mechanism of how these drugs alter fluid secretion in the gut and induce diarrhea
      is not clearly understood. Several drugs are either substrates or inhibitors of
      multidrug resistance protein 4 (MRP4), such as the anti-colon cancer drug
      irinotecan and an anti-retroviral used to treat HIV infection, 3'-azido-3'
      deoxythymidine (AZT). These drugs activate cystic fibrosis transmembrane
      conductance regulator (CFTR)-mediated fluid secretion by inhibiting MRP4-mediated
      cAMP efflux. Binding of drugs to MRP4 augments the formation of MRP4-CFTR
      containing macromolecular complexes that is mediated via scaffolding protein
      PDZK1. Importantly, HIV patients on AZT treatment demonstrate augmented MRP4-CFTR
      complex formation in the colon, which defines a novel paradigm of drug-induced
      diarrhea. 

PMID- 25762724
TI  - Characterization of phospholipids in insulin secretory granules and mitochondria
      in pancreatic beta cells and their changes with glucose stimulation.
AB  - The lipid composition of insulin secretory granules (ISG) has never previously
      been thoroughly characterized. We characterized the phospholipid composition of
      ISG and mitochondria in pancreatic beta cells without and with glucose
      stimulation. The phospholipid/protein ratios of most phospholipids containing
      unsaturated fatty acids were higher in ISG than in whole cells and in
      mitochondria. The concentrations of negatively charged phospholipids,
      phosphatidylserine, and phosphatidylinositol in ISG were 5-fold higher than in
      the whole cell. In ISG phosphatidylserine, phosphatidylinositol,
      phosphatidylethanolamine, and sphingomyelin, fatty acids 12:0 and 14:0 were high,
      as were phosphatidylserine and phosphatidylinositol containing 18-carbon
      unsaturated FA. With glucose stimulation, the concentration of many ISG
      phosphatidylserines and phosphatidylinositols increased; unsaturated fatty acids
      in phosphatidylserine increased; and most phosphatidylethanolamines,
      phosphatidylcholines, sphingomyelins, and lysophosphatidylcholines were
      unchanged. Unsaturation and shorter fatty acid length in phospholipids facilitate
      curvature and fluidity of membranes, which favors fusion of membranes. Recent
      evidence suggests that negatively charged phospholipids, such as
      phosphatidylserine, act as coupling factors enhancing the interaction of
      positively charged regions in SNARE proteins in synaptic or secretory vesicle
      membrane lipid bilayers with positively charged regions in SNARE proteins in the
      plasma membrane lipid bilayer to facilitate docking of vesicles to the plasma
      membrane during exocytosis. The results indicate that ISG phospholipids are in a
      dynamic state and are consistent with the idea that changes in ISG phospholipids
      facilitate fusion of ISG with the plasma membrane-enhancing glucose-stimulated
      insulin exocytosis. 

PMID- 25762725
TI  - Chryseobacterium shandongense sp. nov., isolated from soil.
AB  - YF-3T is a Gram-stain-negative, non-motile, non-spore-forming, yellow-orange, rod
      shaped bacterium. Optimal growth conditions were at 30  degrees C, pH 7.0 and 1 %
      (w/v) NaCl. Phylogenetic analysis, on the basis of the 16S rRNA gene sequence,
      showed that strain YF-3T was closely related to the strains Chryseobacterium
      hispalense AG13T and Chryseobacterium taiwanense Soil-3-27T with 98.71 % and
      96.93 % sequence similarity, respectively. Strain YF-3T contained MK-6 as the
      main menaquinone and had a polyamine pattern with sym-homospermidine as the major
      component. Its major polar lipid was phosphatidylethanolamine. The dominant fatty
      acids of strain YF-3T were iso-C15 : 0, iso-C17 : 0 3-OH, summed feature 9
      (comprising iso-C17 : 1omega9c and/or C16 : 0 10-methyl) and summed feature 3
      (comprising C16 : 1omega7c and/or C16 : 1omega6c). The DNA G+C content of strain
      YF-3T was 37 mol%. The DNA-DNA relatedness levels between strain YF-3T and the
      most closely related strains, C. hispalense AG13T and C. taiwanense Soil-3-27T,
      were 31.7 +/- 2.1 % and 28.4 +/- 5.4 %, respectively. Based on these results, a
      novel species named Chryseobacterium shandongense sp. nov. is proposed. The type
      strain is YF-3T ( = CCTCC AB 2014060T = JCM 30154T).

PMID- 25762726
TI  - Nrf2 up-regulates the induction of acidic sphingomyelinase by electrophiles.
AB  - Acidic sphingomyelinase (ASMase) catalyses the generation of ceramide from
      sphingomyelin. Ceramide is a lipid mediator and is implicated in mediating and
      regulating various cellular processes including cell proliferation,
      differentiation, stress response and inflammation. We have previously reported
      that electrophiles including diethyl maleate (DEM), heavy metals and cigarette
      smoke extracts induced ASMase expression in human bladder carcinoma ECV-304
      cells, but the mechanism of ASMase mRNA induction by electrophiles remains
      unknown. In this study, we clarified the involvement of NF-E2-related factor 2
      (Nrf2) in the induction of ASMase mRNA by DEM. Promoter analysis using a series
      of deletion mutants of the human ASMase gene showed that ARE-like element1
      located in a region between -200 and -160 bp upstream of the transcription start
      point is mainly a DEM-responsive element. Moreover, an electrophoretic mobility
      shift assay using ARE-like element1 revealed that Nrf2 is a candidate
      transcription factor that binds to ARE-like element1 in response to DEM. Finally,
      alteration of Nrf2 expression by overexpression and knockdown could regulate the
      induction of ASMase mRNA by DEM. This is the first evidence that supports the
      possibility that sphingolipid metabolism is affected via the induction of ASMase
      by the Nrf2 pathway. 

PMID- 25762727
TI  - Arkadia enhances BMP signalling through ubiquitylation and degradation of Smad6.
AB  - Arkadia, a positive regulator of Smad-dependent signalling via the transforming
      growth factor-beta (TGF-beta) family, is an E3 ubiquitin ligase that induces
      ubiquitylation and proteasome-dependent degradation of TGF-beta suppressors such
      as Smad7, c-Ski and SnoN. In this study, we examined the effects of Arkadia on
      bone morphogenetic protein (BMP)-induced osteoblast differentiation. Knockdown of
      Arkadia reduced mineralization and expression of osteoblast differentiation
      markers. Furthermore, we showed that Smad6, a BMP-specific inhibitory Smad, is a
      target of Arkadia: wild-type (WT) Arkadia, but not the C937A (CA) mutant lacking
      E3 ubiquitin-ligase activity, induced ubiquitylation and proteasome-dependent
      degradation of Smad6. Accordingly, protein levels of Smad6, Smad7 and c-Ski were
      elevated in MEFs from Arkadia KO mice. Finally, expression of Arkadia attenuated
      blockade of BMP signalling by Smad6 in a transcriptional reporter assay. These
      results demonstrate that Smad6 is a novel target of Arkadia, and that Arkadia
      positively regulates BMP signalling via degradation of Smad6, Smad7 and c
      Ski/SnoN. 

PMID- 25762728
TI  - Engineering of a 3'-sulpho-Galbeta1-4GlcNAc-specific probe by a single amino acid
      substitution of a fungal galectin.
AB  - Among sulphated glycans, little is known about 3'-sulphation because of the lack
      of useful probes. In the course of molecular engineering of a fungal galectin
      from Agrocybe cylindracea, we found that a single substitution of Glu86 with
      alanine resulted in acquisition of specific binding for the 3'-sulpho-Galbeta1
      4GlcNAc structure. Extensive glyco-technological analysis revealed that this
      property was obtained in a 'loss-of-function' manner. Though this mutant (E86A)
      had low total affinity, it showed substantial binding to a naturally occurring N
      glycan, of which the terminal galactose is 3-sulphated. Moreover, E86A
      specifically bound to HeLa cells, in which galactose-3-O-sulfotransferases
      (Gal3ST2 or Gal3ST3) were over-expressed. 

PMID- 25762729
TI  - Prostate biopsy concordance in a large population-based sample: a Surveillance,
      Epidemiology and End Results study.
AB  - AIMS: To use the Surveillance, Epidemiology and End Results database in order to
      evaluate prostate biopsy concordance in a large population-based sample. METHODS:
      We identified 34 195 men who were diagnosed with prostate cancer and underwent a
      radical prostatectomy from 2010 to 2011. All patients also had to have both
      clinical and pathological Gleason scores available for analysis. The concordance
      of the biopsy Gleason score to the pathological Gleason score was analysed using
      the coefficient of agreement (kappa). Univariate and multivariate logistic
      regression analyses were performed to determine potential factors that may impact
      concordance of Gleason score. RESULTS: Overall, the clinical and pathological
      Gleason scores matched in 55.4% of patients. The concordance rates were 55.3% for
      Gleason 6, 66.9% for Gleason 3+4, 42.9% for Gleason 4+3 and 24.8% for Gleason 8,
      with frequent downgrading to Gleason 7. The kappa for Gleason score concordance
      was 0.36 (95% CI 0.35 to 0.37), indicating fair agreement. The weighted kappa for
      Gleason score concordance was 0.51 (95% CI 0.50 to 0.52), indicating moderate
      agreement. Additionally, the Bowker tests of symmetry were highly significant
      (p<0.001), indicating that when discordant findings were present, pathological
      upgrading was more common than downgrading. CONCLUSIONS: This study is, to our
      knowledge, the largest contemporary study of prostate biopsy concordance. We
      found that there continues to be significant Gleason migration both upward from
      biopsy Gleason 6 or 3+4 and downgrading from biopsy Gleason >=8. Further studies
      are needed to better determine other potential genomic or biologic factors that
      may help increase the biopsy Gleason concordance.

PMID- 25762730
TI  - The Road Less Traveled: HIV's Use of Alternative Routes through Cellular
      Pathways.
AB  - Pathogens such as HIV-1, with their minimalist genomes, must navigate cellular
      networks and rely on hijacking and manipulating the host machinery for successful
      replication. Limited overlap of host factors identified as vital for pathogen
      replication may be explained by considering that pathogens target, rather than
      specific cellular factors, crucial cellular pathways by targeting different,
      functionally equivalent, protein-protein interactions within that pathway. The
      ability to utilize alternative routes through cellular pathways may be essential
      for pathogen survival when restricted and provide flexibility depending on the
      viral replication stage and the environment in the infected host. In this
      minireview, we evaluate evidence supporting this notion, discuss specific HIV-1
      examples, and consider the molecular mechanisms which allow pathogens to flexibly
      exploit different routes. 

PMID- 25762731
TI  - Dynamics of Human Cytomegalovirus Infection in CD34+ Hematopoietic Cells and
      Derived Langerhans-Type Dendritic Cells.
AB  - Acquisition of human cytomegalovirus (CMV) usually occurs by contact between
      contaminated bodily fluids, such as urine and saliva, and host mucosal cells.
      Langerhans-type dendritic cells (LC) are the only type of immune cells found in
      the outermost layers of the oral mucosae, where they not only provide a first
      line of defense against CMV but can easily be targeted by orally administered
      vaccines, while their bone marrow resident progenitors are important sites of
      virus latency. In this work, we tracked the progress of infection in CD34(+)
      progenitor cells, immature LC (iLC), and mature LC (mLC) exposed to the clinical
      like strain TB40-BAC4 or to the vaccine strain AD169varATCC, prior to their long
      term maintenance under either immature or mature conditions. We show that the
      genomes of both strains are efficiently maintained in CD34(+) cells during their
      differentiation into iLC, although this requires the presence of larger amounts
      of input AD169varATCC DNA. Lipopolysaccharide- and CD40 ligand-induced maturation
      of iLC derived from latently infected progenitors was not associated with robust
      viral genome replication and progeny production, while maturation of directly
      infected iLC increased and prolonged expression of the viral immediate early
      proteins. While effective replication of viral genomes from both strains occurred
      only in mLC, both iLC and mLC produced viral progeny, suggesting that both types
      of LC may contribute to CMV horizontal transmission in vivo. IMPORTANCE: Human
      CMV is usually acquired via the oral and nasal mucosae. Langerhans-type dendritic
      cells (LC) are the only type of immune cells found in the outermost layers of
      these tissues. Understanding how CMV interacts with LC and their hematopoietic
      progenitors is thus essential to develop innovative means of defense against this
      virus. Here we show that the genomes of a virulent and an attenuated strain of
      CMV are maintained in hematopoietic progenitor cells during their differentiation
      into immature LC and that maturation of these cells by exposure to
      lipopolysaccharide and CD40 ligand is not sufficient to trigger virus
      reactivation. While the extents of viral protein expression and genome
      replication were broadest in directly infected mature LC populations, similar
      amounts of viral progeny were detected in the supernatants of immature and mature
      LC, suggesting that these immune cells of the oral mucosa are likely to be
      important for CMV transmission within the human population.

PMID- 25762732
TI  - Dengue Virus Evolution under a Host-Targeted Antiviral.
AB  - The host-targeted antiviral drug UV-4B reduces viral replication and promotes
      survival in a mouse model of experimental dengue virus (DENV) infection. UV-4B is
      an iminosugar that inhibits the alpha-glucosidase family of enzymes and
      subsequently the folding of glycosylated proteins, both viral and host. Here, we
      utilized next-generation sequencing to investigate evolution of a flavivirus
      under selective pressure by a host-targeted antiviral in vivo. In viral
      populations recovered from UV-4B-treated mice, there was a significant increase
      in the number of single-nucleotide polymorphisms (SNPs) and the ratio of
      nonsynonymous to synonymous SNPs compared to findings in viral populations from
      vehicle-treated mice. The strongest evidence of positive selection was in the
      glycosylated membrane protein, thereby providing in vivo validation of the
      mechanism of action of an iminosugar. In addition, mutations in glycosylated
      proteins were present only in drug-treated mice after a single passage. However,
      the bulk of the other mutations were present in both populations, indicating
      nonspecific selective pressure. Together with the continued control of viremia by
      UV-4B, these findings are consistent with the previously predicted high genetic
      barrier to escape mutations in host-targeted antivirals. IMPORTANCE: Although
      hundreds of millions of people are infected with DENV every year, there is
      currently no approved vaccine or antiviral therapy. UV-4B has demonstrated
      antiviral activity against DENV and is expected to enter clinical trials soon.
      Therefore, it is important to understand the mechanisms of DENV resistance to UV
      4B. Host-targeted antivirals are thought to have a higher genetic barrier to
      escape mutants than directly acting antivirals, yet there are very few published
      studies of viral evolution under host-targeted antivirals. No study to date has
      described flavivirus evolution in vivo under selective pressure by a host-based
      antiviral drug. We present the first in vivo study of the sequential progression
      of viral evolution under selective pressure by a host-targeted antiviral
      compound. This study bolsters support for the clinical development of UV-4B as an
      antiviral drug against DENV, and it provides a framework to compare how treatment
      with other host-targeted antiflaviviral drugs in humans and different animal
      models influence viral genetic diversity.

PMID- 25762734
TI  - Latent herpes simplex virus 1 infection does not induce apoptosis in human
      trigeminal Ganglia.
AB  - Herpes simplex virus 1 (HSV-1) can establish lifelong latency in human trigeminal
      ganglia. Latently infected ganglia contain CD8(+) T cells, which secrete granzyme
      B and are thus capable of inducing neuronal apoptosis. Using immunohistochemistry
      and single-cell reverse transcription-quantitative PCR (RT-qPCR), higher
      frequency and transcript levels of caspase-3 were found in HSV-1-negative
      compared to HSV-1-positive ganglia and neurons, respectively. No terminal
      deoxynucleotidyltransferase-mediated dUTP-biotin nick end labeling (TUNEL) assay
      positive neurons were detected. The infiltrating T cells do not induce apoptosis
      in latently infected neurons. 

PMID- 25762733
TI  - Viral Infection of the Central Nervous System and Neuroinflammation Precede Blood
      Brain Barrier Disruption during Japanese Encephalitis Virus Infection.
AB  - Japanese encephalitis is an acute zoonotic, mosquito-borne disease caused by
      Japanese encephalitis virus (JEV). Japanese encephalitis is characterized by
      extensive inflammation in the central nervous system (CNS) and disruption of the
      blood-brain barrier (BBB). However, the pathogenic mechanisms contributing to the
      BBB disruption are not known. Here, using a mouse model of intravenous JEV
      infection, we show that virus titers increased exponentially in the brain from 2
      to 5 days postinfection. This was accompanied by an early, dramatic increase in
      the level of inflammatory cytokines and chemokines in the brain. Enhancement of
      BBB permeability, however, was not observed until day 4, suggesting that viral
      entry and the onset of inflammation in the CNS occurred prior to BBB damage. In
      vitro studies revealed that direct infection with JEV could not induce changes in
      the permeability of brain microvascular endothelial cell monolayers. However,
      brain extracts derived from symptomatic JEV-infected mice, but not from mock
      infected mice, induced significant permeability of the endothelial monolayer.
      Consistent with a role for inflammatory mediators in BBB disruption, the
      administration of gamma interferon-neutralizing antibody ameliorated the
      enhancement of BBB permeability in JEV-infected mice. Taken together, our data
      suggest that JEV enters the CNS, propagates in neurons, and induces the
      production of inflammatory cytokines and chemokines, which result in the
      disruption of the BBB. IMPORTANCE: Japanese encephalitis (JE) is the leading
      cause of viral encephalitis in Asia, resulting in 70,000 cases each year, in
      which approximately 20 to 30% of cases are fatal, and a high proportion of
      patients survive with serious neurological and psychiatric sequelae.
      Pathologically, JEV infection causes an acute encephalopathy accompanied by BBB
      dysfunction; however, the mechanism is not clear. Thus, understanding the
      mechanisms of BBB disruption in JEV infection is important. Our data demonstrate
      that JEV gains entry into the CNS prior to BBB disruption. Furthermore, it is not
      JEV infection per se, but the inflammatory cytokines/chemokines induced by JEV
      infection that inhibit the expression of TJ proteins and ultimately result in the
      enhancement of BBB permeability. Neutralization of gamma interferon (IFN-gamma)
      ameliorated the enhancement of BBB permeability in JEV-infected mice, suggesting
      that IFN-gamma could be a potential therapeutic target. This study would lead to
      identification of potential therapeutic avenues for the treatment of JEV
      infection.

PMID- 25762735
TI  - The pH Stability of Foot-and-Mouth Disease Virus Particles Is Modulated by
      Residues Located at the Pentameric Interface and in the N Terminus of VP1.
AB  - The picornavirus foot-and-mouth disease virus (FMDV) is the etiological agent of
      a highly contagious disease that affects important livestock species. The FMDV
      capsid is highly acid labile, and viral particles lose infectivity due to their
      disassembly at pH values slightly below neutrality. This acid sensitivity is
      related to the mechanism of viral uncoating and genome penetration from
      endosomes. In this study, we have analyzed the molecular basis of FMDV acid
      induced disassembly by isolating and characterizing a panel of novel FMDV mutants
      differing in acid sensitivity. Amino acid replacements altering virion stability
      were preferentially distributed in two different regions of the capsid: the N
      terminus of VP1 and the pentameric interface. Even more, the acid labile
      phenotype induced by a mutation located at the pentameric interface in VP3 could
      be compensated by introduction of an amino acid substitution in the N terminus of
      VP1. These results indicate that the acid sensitivity of FMDV can be considered a
      multifactorial trait and that virion stability is the fine-tuned product of the
      interaction between residues from different capsid proteins, in particular those
      located within the N terminus of VP1 or close to the pentameric interface.
      IMPORTANCE: The viral capsid protects the viral genome from environmental factors
      and contributes to virus dissemination and infection. Thus, understanding of the
      molecular mechanisms that modulate capsid stability is of interest for the basic
      knowledge of the biology of viruses and as a tool to improve the stability of
      conventional vaccines based on inactivated virions or empty capsids. Using foot
      and-mouth disease virus (FMDV), which displays a capsid with extreme acid
      sensitivity, we have performed a genetic study to identify the molecular
      determinants involved in capsid stability. A panel of FMDV mutants with
      differential sensitivity to acidic pH was generated and characterized, and the
      results showed that two different regions of FMDV capsid contribute to modulating
      viral particle stability. These results provide new insights into the molecular
      mechanisms of acid-mediated FMDV uncoating.

PMID- 25762736
TI  - Tristetraprolin Recruits the Herpes Simplex Virion Host Shutoff RNase to AU-Rich
      Elements in Stress Response mRNAs To Enable Their Cleavage.
AB  - Herpes simplex viruses (HSV) package and bring into cells an RNase designated
      virion host shutoff (VHS) RNase. In infected cells, the VHS RNase targets
      primarily stress response mRNAs characterized by the presence of AU-rich elements
      in their 3' untranslated regions (UTRs). In uninfected cells, these RNAs are
      sequestered in exosomes or P bodies by host proteins that bind to the AU-rich
      elements. In infected cells, the AU-rich RNAs are deadenylated and cleaved close
      to the AU-rich elements, leading to long-term persistence of nontranslatable RNAs
      consisting of the 5' portions of the cleavage products. The host proteins that
      bind to the AU-rich elements are either resident in cells (e.g., TIA-1) or
      induced (e.g., tristetraprolin). Earlier, this laboratory reported that
      tristetraprolin binds VHS RNase. To test the hypothesis that tristetraprolin
      directs VHS RNase to the AU-rich elements, we mapped the domains of VHS and
      tristetraprolin required for their interactions. We report that VHS binds to the
      domain of tristetraprolin that enables its interaction with RNA. A single amino
      acid substitution in that domain abolished the interaction with RNA but did not
      block the binding to VHS RNase. In transfected cells, the mutant but not the wild
      type tristetraprolin precluded the degradation of the AU-rich RNAs by VHS RNase.
      We conclude that TTP mediates the cleavage of the 3' UTRs of stress response
      mRNAs by recruiting the VHS RNase to the AU-rich elements. IMPORTANCE: The
      primary host response to HSV infection is the synthesis of stress response mRNAs
      characterized by the presence of AU-rich elements in their 3' UTRs. These mRNAs
      are the targets of the virion host shutoff (VHS) RNase. The VHS RNase binds both
      to mRNA cap structure and to tristetraprolin, an inducible host protein that
      sequesters AU-rich mRNAs in exosomes or P bodies. Here we show that
      tristetraprolin recruits VHS RNase to the AU-rich elements and enables the
      degradation of the stress response mRNAs.

PMID- 25762739
TI  - Structure and Dynamics of the Native HIV-1 Env Trimer.
AB  - HIV-1/AIDS remains one of the worst pandemics in human history. Despite
      tremendous efforts, no effective vaccine has been found. Recent reports give new
      insights into the structure and dynamics of the HIV-1 Env trimer and renew hopes
      that a better understanding of Env will translate into new vaccine candidates and
      more-effective antiretroviral therapies. 

PMID- 25762737
TI  - Swine Influenza Virus PA and Neuraminidase Gene Reassortment into Human H1N1
      Influenza Virus Is Associated with an Altered Pathogenic Phenotype Linked to
      Increased MIP-2 Expression.
AB  - Swine are susceptible to infection by both avian and human influenza viruses, and
      this feature is thought to contribute to novel reassortant influenza viruses. In
      this study, the influenza virus reassortment rate in swine and human cells was
      determined. Coinfection of swine cells with 2009 pandemic H1N1 virus (huH1N1) and
      an endemic swine H1N2 (A/swine/Illinois/02860/09) virus (swH1N2) resulted in a
      23% reassortment rate that was independent of alpha2,3- or alpha2,6-sialic acid
      distribution on the cells. The reassortants had altered pathogenic phenotypes
      linked to introduction of the swine virus PA and neuraminidase (NA) into huH1N1.
      In mice, the huH1N1 PA and NA mediated increased MIP-2 expression early
      postinfection, resulting in substantial pulmonary neutrophilia with enhanced lung
      pathology and disease. The findings support the notion that swine are a mixing
      vessel for influenza virus reassortants independent of sialic acid distribution.
      These results show the potential for continued reassortment of the 2009 pandemic
      H1N1 virus with endemic swine viruses and for reassortants to have increased
      pathogenicity linked to the swine virus NA and PA genes which are associated with
      increased pulmonary neutrophil trafficking that is related to MIP-2 expression.
      IMPORTANCE: Influenza A viruses can change rapidly via reassortment to create a
      novel virus, and reassortment can result in possible pandemics. Reassortments
      among subtypes from avian and human viruses led to the 1957 (H2N2 subtype) and
      1968 (H3N2 subtype) human influenza pandemics. Recent analyses of circulating
      isolates have shown that multiple genes can be recombined from human, avian, and
      swine influenza viruses, leading to triple reassortants. Understanding the
      factors that can affect influenza A virus reassortment is needed for the
      establishment of disease intervention strategies that may reduce or preclude
      pandemics. The findings from this study show that swine cells provide a mixing
      vessel for influenza virus reassortment independent of differential sialic acid
      distribution. The findings also establish that circulating neuraminidase (NA) and
      PA genes could alter the pathogenic phenotype of the pandemic H1N1 virus,
      resulting in enhanced disease. The identification of such factors provides a
      framework for pandemic modeling and surveillance.

PMID- 25762738
TI  - Structure-based mutational analysis of several sites in the E protein:
      implications for understanding the entry mechanism of Japanese encephalitis
      virus.
AB  - Japanese encephalitis virus (JEV), which causes viral encephalitis in humans, is
      a serious risk to global public health. The JEV envelope protein mediates the
      viral entry pathway, including receptor-binding and low-pH-triggered membrane
      fusion. Utilizing mutagenesis of a JEV infectious cDNA clone, mutations were
      introduced into the potential receptor-binding motif or into residues critical
      for membrane fusion in the envelope protein to systematically investigate the JEV
      entry mechanism. We conducted experiments evaluating infectious particle,
      recombinant viral particle, and virus-like particle production and found that
      most mutations impaired virus production. Subcellular fractionation confirmed
      that five mutations--in I0, ij, BC, and FG and the R9A substitution-impaired
      virus assembly, and the assembled virus particles of another five mutations--in
      kl and the E373A, F407A, L221S, and W217A substitutions--were not released into
      the secretory pathway. Next, we examined the entry activity of six mutations
      yielding infectious virus. The results showed N154 and the DE loop are not the
      only or major receptor-binding motifs for JEV entry into BHK-21 cells; four
      residues, H144, H319, T410, and Q258, participating in the domain I (DI)-DIII
      interaction or zippering reaction are important to maintain the efficiency of
      viral membrane fusion. By continuous passaging of mutants, adaptive mutations
      from negatively charged amino acids to positively charged or neutral amino acids,
      such as E138K and D389G, were selected and could restore the viral entry
      activity. IMPORTANCE: Recently, there has been much interest in the entry
      mechanism of flaviviruses into host cells, including the viral entry pathway and
      membrane fusion mechanism. Our study provides strong evidence for the critical
      role of several residues in the envelope protein in the assembly, release, and
      entry of JEV, which also contributes to our understanding of the flaviviral entry
      mechanism. Furthermore, we demonstrate that the H144A, H319A, T410A, and Q258A
      mutants exhibit attenuated fusion competence, which may be used to develop novel
      vaccine candidates for flaviviruses.

PMID- 25762740
TI  - Efficient Interaction between Arenavirus Nucleoprotein (NP) and RNA-Dependent RNA
      Polymerase (L) Is Mediated by the Virus Nucleocapsid (NP-RNA) Template.
AB  - In this study, we document that efficient interaction between arenavirus
      nucleoprotein (NP) and RNA-dependent RNA polymerase (L protein), the two trans
      acting viral factors required for both virus RNA replication and gene
      transcription, requires the presence of virus-specific RNA sequences located
      within the untranslated 5' and 3' termini of the viral genome. 

PMID- 25762741
TI  - Degradation of SAMHD1 by Vpx Is Independent of Uncoating.
AB  - Sterile alpha motif domain and HD domain-containing protein 1 (SAMHD1) restricts
      human immunodeficiency virus type 1 (HIV-1) replication in myeloid and resting T
      cells. Lentiviruses such as HIV-2 and some simian immunodeficiency viruses (SIVs)
      counteract the restriction by encoding Vpx or Vpr, accessory proteins that are
      packaged in virions and which, upon entry of the virus into the cytoplasm, induce
      the proteasomal degradation of SAMHD1. As a tool to study these mechanisms, we
      generated HeLa cell lines that express a fusion protein termed NLS.GFP.SAM595 in
      which the Vpx binding domain of SAMHD1 is fused to the carboxy terminus of green
      fluorescent protein (GFP) and a nuclear localization signal is fused to the amino
      terminus of GFP. Upon incubation of Vpx-containing virions with the cells, the
      NLS.GFP.SAM595 fusion protein was degraded over several hours and the levels
      remained low over 5 days as the result of continued targeting of the CRL4 E3
      ubiquitin ligase. Degradation of the fusion protein required that it contain a
      nuclear localization sequence. Fusion to the cytoplasmic protein muNS rendered
      the protein resistant to Vpx-mediated degradation, confirming that SAMHD1 is
      targeted in the nucleus. Virions treated with protease inhibitors failed to
      release Vpx, indicating that Gag processing was required for Vpx release from the
      virion. Mutations in the capsid protein that altered the kinetics of virus
      uncoating and the Gag binding drug PF74 had no effect on the Vpx-mediated
      degradation. These results suggest that Vpx is released from virions without a
      need for uncoating of the capsid, allowing Vpx to transit to the nucleus rapidly
      upon entry into the cytoplasm. IMPORTANCE: SAMHD1 restricts lentiviral
      replication in myeloid cells and resting T cells. Its importance is highlighted
      by the fact that viruses such as HIV-2 encode an accessory protein that is
      packaged in the virion and is dedicated to inducing SAMHD1 degradation. Vpx needs
      to act rapidly upon infection to allow reverse transcription to proceed. The
      limited number of Vpx molecules in a virion also needs to clear the cell of
      SAMHD1 over a prolonged period of time. Using an engineered HeLa cell line that
      expresses a green fluorescent protein (GFP)-SAMHD1 fusion protein, we showed that
      the Vpx-dependent degradation occurs without a need for viral capsid uncoating.
      In addition, the fusion protein was degraded only when it was localized to the
      nucleus, confirming that SAMHD1 is targeted in the nucleus and thus explaining
      why Vpx also localizes to the nucleus.

PMID- 25762743
TI  - Murine Gammaherpesvirus 68 ORF48 Is an RTA-Responsive Gene Product and Functions
      in both Viral Lytic Replication and Latency during In Vivo Infection.
AB  - Replication and transcription activator (RTA) of gammaherpesvirus is an immediate
      early gene product and regulates the expression of many downstream viral lytic
      genes. ORF48 is also conserved among gammaherpesviruses; however, its expression
      regulation and function remained largely unknown. In this study, we characterized
      the transcription unit of ORF48 from murine gammaherpesvirus 68 (MHV-68) and
      analyzed its transcriptional regulation. We showed that RTA activates the ORF48
      promoter via an RTA-responsive element (48pRRE). RTA binds to 48pRRE directly in
      vitro and also associates with ORF48 promoter in vivo. Mutagenesis of 48pRRE in
      the context of the viral genome demonstrated that the expression of ORF48 is
      activated by RTA through 48pRRE during de novo infection. Through site-specific
      mutagenesis, we generated an ORF48-null virus and examined the function of ORF48
      in vitro and in vivo. The ORF48-null mutation remarkably reduced the viral
      replication efficiency in cell culture. Moreover, through intranasal or
      intraperitoneal infection of laboratory mice, we showed that ORF48 is important
      for viral lytic replication in the lung and establishment of latency in the
      spleen, as well as viral reactivation from latency. Collectively, our study
      identified ORF48 as an RTA-responsive gene and showed that ORF48 is important for
      MHV-68 replication both in vitro and in vivo. IMPORTANCE: The replication and
      transcription activator (RTA), conserved among gammaherpesviruses, serves as a
      molecular switch for the virus life cycle. It works as a transcriptional
      regulator to activate the expression of many viral lytic genes. However, only a
      limited number of such downstream genes have been uncovered for MHV-68. In this
      study, we identified ORF48 as an RTA-responsive gene of MHV-68 and mapped the cis
      element involved. By constructing a mutant virus that is deficient in ORF48
      expression and through infection of laboratory mice, we showed that ORF48 plays
      important roles in different stages of viral infection in vivo. Our study
      provides insights into the transcriptional regulation and protein function of MHV
      68, a desired model for studying gammaherpesviruses.

PMID- 25762742
TI  - Activation of Tomato Bushy Stunt Virus RNA-Dependent RNA Polymerase by Cellular
      Heat Shock Protein 70 Is Enhanced by Phospholipids In Vitro.
AB  - Similar to other positive-strand RNA viruses, tombusviruses are replicated by the
      membrane-bound viral replicase complex (VRC). The VRC consists of the p92 virus
      coded RNA-dependent RNA polymerase (RdRp), the viral p33 RNA chaperone, and
      several co-opted host proteins. In order to become a functional RdRp after its
      translation, the p92 replication protein should be incorporated into the VRC,
      followed by its activation. We have previously shown in a cell-free yeast extract
      based assay that the activation of the Tomato bushy stunt virus (TBSV) RdRp
      requires a soluble host factor(s). In this article, we identify the cellular heat
      shock protein 70 (Hsp70) as the co-opted host factor required for the activation
      of an N-terminally truncated recombinant TBSV RdRp. In addition, small-molecule
      based blocking of Hsp70 function inhibits RNA synthesis by the tombusvirus RdRp
      in vitro. Furthermore, we show that neutral phospholipids, namely,
      phosphatidylethanolamine (PE) and phosphatidylcholine (PC), enhance RdRp
      activation in vitro. In contrast, phosphatidylglycerol (PG) shows a strong and
      dominant inhibitory effect on in vitro RdRp activation. We also demonstrate that
      PE and PC stimulate RdRp-viral plus-strand RNA [(+)RNA] interaction, while PG
      inhibits the binding of the viral RNA to the RdRp. Based on the stimulatory
      versus inhibitory roles of various phospholipids in tombusvirus RdRp activation,
      we propose that the lipid composition of targeted subcellular membranes might be
      utilized by tombusviruses to regulate new VRC assembly during the course of
      infection. IMPORTANCE: The virus-coded RNA-dependent RNA polymerase (RdRp), which
      is responsible for synthesizing the viral RNA progeny in infected cells of
      several positive-strand RNA viruses, is initially inactive. This strategy is
      likely to avoid viral RNA synthesis in the cytosol that would rapidly lead to
      induction of RNA-triggered cellular antiviral responses. During the assembly of
      the membrane-bound replicase complex, the viral RdRp becomes activated through an
      incompletely understood process that makes the RdRp capable of RNA synthesis. By
      using TBSV RdRp, we show that the co-opted cellular Hsp70 chaperone and neutral
      phospholipids facilitate RdRp activation in vitro. In contrast,
      phosphatidylglycerol (PG) has a dominant inhibitory effect on in vitro RdRp
      activation and RdRp-viral RNA interaction, suggesting that the membranous
      microdomain surrounding the RdRp greatly affects its ability for RNA synthesis.
      Thus, the activation of the viral RdRp likely depends on multiple host components
      in infected cells.

PMID- 25762745
TI  - Direct inoculation of positive blood cultures using the Phoenix system for
      antimicrobial susceptibility testing of both Gram-positive and Gram-negative
      bacteria.

PMID- 25762744
TI  - Quantitative Proteomics Analysis Reveals Novel Insights into Mechanisms of Action
      of Long Noncoding RNA Hox Transcript Antisense Intergenic RNA (HOTAIR) in HeLa
      Cells.
AB  - Long noncoding RNAs (lncRNAs), which have emerged in recent years as a new and
      crucial layer of gene regulators, regulate various biological processes such as
      carcinogenesis and metastasis. HOTAIR (Hox transcript antisense intergenic RNA),
      a lncRNA overexpressed in most human cancers, has been shown to be an oncogenic
      lncRNA. Here, we explored the role of HOTAIR in HeLa cells and searched for
      proteins regulated by HOTAIR. To understand the mechanism of action of HOTAIR
      from a systems perspective, we employed a quantitative proteomic strategy to
      systematically identify potential targets of HOTAIR. The expression of 170
      proteins was significantly dys-regulated after inhibition of HOTAIR, implying
      that they could be potential targets of HOTAIR. Analysis of this data at the
      systems level revealed major changes in proteins involved in diverse cellular
      components, including the cytoskeleton and the respiratory chain. Further
      functional studies on vimentin (VIM), a key protein involved in the cytoskeleton,
      revealed that HOTAIR exerts its effects on migration and invasion of HeLa cells,
      at least in part, through the regulation of VIM expression. Inhibition of HOTAIR
      leads to mitochondrial dysfunction and ultrastructural alterations, suggesting a
      novel role of HOTAIR in maintaining mitochondrial function in cancer cells. Our
      results provide novel insights into the mechanisms underlying the function of
      HOTAIR in cancer cells. We expect that the methods used in this study will become
      an integral part of functional studies of lncRNAs. 

PMID- 25762746
TI  - Innovations in translational sex and gender-sensitive tobacco research.

PMID- 25762747
TI  - Sex differences in hormonal responses to stress and smoking relapse: a
      prospective examination.
AB  - INTRODUCTION: Dysregulation in the hypothalamic-pituitary-adrenal axis has been
      shown to be associated with smoking relapse. No study has directly examined the
      role of sex differences in this relationship. METHODS: Nicotine dependent men (n
      = 52) and women (n = 46) interested in cessation completed 2 laboratory stress
      sessions during ad libitum smoking and after 48 hr of abstinence. The laboratory
      session included baseline, stress, and recovery periods. Blood and saliva samples
      were collected at the end of each period for the measurement of cortisol and
      adrenocorticotropic hormone. Self-report measures of craving and withdrawal
      symptoms were also collected. Participants attended 4 weekly follow-up sessions
      for counseling where they provided biological samples and self-report measures
      including smoking status. Relapse was defined by smoking cigarettes for 7
      consecutive days post-cessation. RESULTS: Results showed that 60 participants
      relapsed during the 4-week period. Cox regression models from the abstinence
      session showed that cortisol levels regardless of source were predictive of
      relapse but the direction of prediction was sex dependent (Sex * Hormone, all ps
      < .05). Follow-up analyses further revealed that lower cortisol levels predicted
      relapse in men whereas greater cortisol levels predicted relapse in women (ps <
      .05). Enhanced craving predicted early smoking relapse in men but not in women
      (ps < .05). Data from the ad libitum session showed no differences in predicting
      relapse. CONCLUSION: These findings highlight that sex differences in the
      hormonal response to stress and subjective craving during nicotine withdrawal are
      critical predictors of risk for understanding early relapse.

PMID- 25762748
TI  - Influence of menstrual cycle phase on neural and craving responses to appetitive
      smoking cues in naturally cycling females.
AB  - INTRODUCTION: Functional magnetic resonance imaging (fMRI) has been used
      extensively in an attempt to understand brain vulnerabilities that mediate
      maladaptive responses to drug cues. Using perfusion fMRI, we have consistently
      shown reward-related activation (medial orbitofrontal cortex/ventral striatum) to
      smoking cues (SCs). Because preclinical and clinical studies generally show that
      progesterone may reduce reward and craving, we hypothesized that females in the
      follicular phase of the cycle (FPs; when progesterone levels are low) would have
      greater reward-related neural responses to SCs compared with females in the
      luteal phase (LPs). METHODS: Sated cigarette-dependent premenopausal naturally
      cycling females underwent pseudo-continuous arterial spin-labeled perfusion fMRI
      during exposure to 10-min audio visual clips of appetitive SCs and non-SCs. Brain
      responses to SCs relative to non-SCs were examined among females grouped
      according to menstrual cycle (MC) phase at the time of scanning (22 FPs, 15 LPs).
      Craving scores were acquired pre- and post-SC exposure. RESULTS: FPs showed
      increased neural responses to SCs compared with non-SCs in the medial
      orbitofrontal cortex (p <= .05 corrected), whereas LPs did not. FPs reported SC
      elicited craving (p <= .005), whereas LPs did not. Within FPs, SC-induced craving
      correlated with increased neural responses in the anterior insula (r = 0.73, p <
      .0001). CONCLUSIONS: FPs may be more vulnerable to relapse during appetitive SC
      exposure than LPs. Because the influence of MC phase on drug cue neural activity
      has not been examined, these results contribute to our knowledge of the
      neurobiological underpinnings of responses to drug cues, and they highlight the
      importance of monitoring menstrual cycle phase in all areas of addiction
      research.

PMID- 25762749
TI  - Increasing progesterone levels are associated with smoking abstinence among free
      cycling women smokers who receive brief pharmacotherapy.
AB  - INTRODUCTION: Preclinical and human laboratory research suggests that (a)
      progesterone may decrease drug reward, craving, and smoking behavior, and (b)
      estradiol may enhance drug reward and smoking behavior. A modest majority of
      treatment research examining the relationship between menstrual cycle phase and
      outcomes suggests that the luteal menstrual phase, with its uniquely higher
      progesterone levels, is associated with better cessation outcomes. However, no
      studies to date have examined the effects of naturally occurring variation in
      progesterone and estradiol levels on medication-assisted smoking cessation. The
      present study sought to fill this notable gap in the treatment literature.
      METHODS: Weekly plasma progesterone and estradiol levels were obtained from
      nicotine-dependent female smokers enrolled in a 4-week cessation trial.
      Participants (N = 108) were randomized to receive a 4-week course of either
      varenicline (VAR) tablets and placebo patches or placebo tablets and nicotine
      patches. Plasma samples were obtained 1 week before their cessation attempt and
      weekly during medication administration. Abstinence was assessed weekly. RESULTS:
      Weekly hormone data replicated commonly observed menstrual cycle patterns of
      progesterone and estradiol levels. Importantly, increases in progesterone level
      were associated with a 23% increase in the odds for being abstinent within each
      week of treatment. This effect was driven primarily by nicotine patch-treated
      versus VAR-treated females. CONCLUSIONS: This study was the first to identify an
      association between progesterone level (increasing) and abstinence outcomes in
      free-cycling women smokers who participated in a medication-based treatment.
      Furthermore, the potential benefits of progesterone may vary across different
      pharmacotherapies. Implications of these findings for smoking cessation
      intervention are discussed.

PMID- 25762750
TI  - Systematic and meta-analytic review of research examining the impact of menstrual
      cycle phase and ovarian hormones on smoking and cessation.
AB  - INTRODUCTION: To determine the effect of ovarian hormones on smoking, we
      conducted a systematic review of menstrual cycle effects on smoking (i.e., ad lib
      smoking, smoking topography, and subjective effects) and cessation-related
      behaviors (i.e., cessation, withdrawal, tonic craving, and cue-induced craving).
      METHODS: Thirty-six papers were identified on MEDLINE that included a menstrual
      related search term (e.g., menstrual cycle, ovarian hormones), a smoking-related
      search term (e.g., smoking, nicotine), and met all inclusion criteria. Thirty-two
      studies examined menstrual phase, 1 study measured hormone levels, and 3 studies
      administered progesterone. RESULTS: Sufficient data were available to conduct
      meta-analyses for only 2 of the 7 variables: withdrawal and tonic craving. Women
      reported greater withdrawal during the luteal phase than during the follicular
      phase, and there was a nonsignificant trend for greater tonic craving in the
      luteal phase. Progesterone administration was associated with decreased positive
      and increased negative subjective effects of nicotine. Studies of menstrual phase
      effects on the other outcome variables were either small in number or yielded
      mixed outcomes. CONCLUSIONS: The impact of menstrual cycle phase on smoking
      behavior and cessation is complicated, and insufficient research is available
      upon which to conduct meta-analyses on most smoking outcomes. Future progress
      will require collecting ovarian hormone levels to more precisely quantify the
      impact of dynamic changes in hormone levels through the cycle on smoking
      behavior. Clarifying the relationship between hormones and smoking-particularly
      related to quitting, relapse, and medication response-could determine the best
      type and timing of interventions to improve quit rates for women.

PMID- 25762751
TI  - Nicotine withdrawal increases stress-associated genes in the nucleus accumbens of
      female rats in a hormone-dependent manner.
AB  - INTRODUCTION: Previous work led to our hypothesis that sex differences produced
      by nicotine withdrawal are modulated by stress and dopamine systems in the
      nucleus accumbens (NAcc). We investigated our hypothesis by studying intact
      females to determine whether the mechanisms that promote withdrawal are ovarian
      hormone mediated. METHODS: Female rats were ovariectomized (OVX) or received sham
      surgery (intact) on postnatal day (PND 45-46). On PND 60, they received sham
      surgery (controls) or were prepared with nicotine pumps. Fourteen days later,
      half of the rats had their pumps removed (nicotine withdrawal) and the other half
      received sham surgery (nicotine exposure). Twenty-four hours later, the rats were
      tested for anxiety-like behavior using the elevated plus maze and light/dark
      transfer procedures. The NAcc was then dissected for analysis of several genes
      related to stress (CRF, UCN, CRF-R1, CRF-R2, CRF-BP, and Arrb2) or receptors for
      dopamine (Drd1 and Drd2) and estradiol (Esr2). RESULTS: During withdrawal, intact
      females displayed an increase in anxiety-like behavior in both tests and CRF,
      UCN, and Drd1 gene expression. During nicotine exposure, intact females displayed
      a decrease in CRF-R1, CRF-R2, Drd3, and Esr2 gene expression and an increase in
      CRF-BP. This pattern of results was absent in OVX females. CONCLUSIONS: Nicotine
      withdrawal produced an increase in anxiety-like behavior and stress-associated
      genes in intact females that is distinct from changes produced by nicotine
      exposure. The latter effects were absent in OVX females, suggesting that stress
      produced by withdrawal is ovarian-hormone mediated. These findings have important
      implications towards understanding tobacco use liability among females.

PMID- 25762752
TI  - Gender and stimulus control of smoking behavior.
AB  - INTRODUCTION: Gender differences in smoking behavior have been proposed to
      account for poorer outcomes among women attempting to quit. Specifically, it has
      been suggested that women's smoking behavior is less motivated by nicotine
      seeking and more driven by environmental cues. To date, however, few real-world
      studies have examined the hypothesis that women's smoking is under greater
      stimulus control. METHODS: One hundred and ninety four daily smokers (men = 107;
      women = 87) completed 3 weeks of ecological momentary assessment (EMA) monitoring
      that provided data on real-world smoking behavior by reporting on situational
      contexts shown by previous research to influence smoking behavior (including
      social setting, cigarette availability, alcohol consumption, and mood). RESULTS:
      Analyses of particular cues found few gender differences; however, men's smoking
      increased to a greater extent compared with women's when they were with others
      who were smoking. Idiographic analyses that allow individual subjects to have
      different directions of linkage to situational cues also were conducted to assess
      how predictable subjects' smoking was from a range of contextual characteristics.
      Compared with women, men's smoking was significantly more closely tied to
      food/alcohol consumption and tended to be more closely tied to social context. No
      other gender differences were found. CONCLUSIONS: EMA analyses suggest that men
      and women are similarly influenced by cues, including mood. Where there were
      gender differences, it was men rather than women whose smoking behavior was more
      influenced by cues. The data contradict the hypothesis that women's smoking is
      more influenced by cues.

PMID- 25762753
TI  - Gender differences in responses to cues presented in the natural environment of
      cigarette smokers.
AB  - INTRODUCTION: Although the evidence is mixed, female smokers appear to have more
      difficulty quitting smoking than male smokers. Craving, stress, and negative
      affect have been hypothesized as potential factors underlying gender differences
      in quit rates. METHODS: In the current study, the cue-reactivity paradigm was
      used to assess craving, stress, and negative affect in response to cues presented
      in the natural environment of cigarette smokers using ecological momentary
      assessment. Seventy-six daily smokers (42% female) responded to photographs
      (smoking, stress, and neutral) presented 4 times per day on an iPhone over the
      course of 2 weeks. RESULTS: Both smoking and stress cues elicited stronger
      cigarette craving and stress responses compared to neutral cues. Compared with
      males, females reported higher levels of post-stress cue craving, stress, and
      negative affect, but response to smoking cues did not differ by gender.
      DISCUSSION: Findings from this project were largely consistent with results from
      laboratory-based research and extend previous work by measuring response to cues
      in the natural environment of cigarette smokers. This study extends previous cue
      reactivity ecological momentary assessment research by using a new platform and
      by measuring response to stress cues outside of the laboratory. Findings from
      this project highlight the importance of addressing coping in response to stress
      cues in clinical settings, especially when working with female smokers.

PMID- 25762754
TI  - Sex differences in acute relief of abstinence-induced withdrawal and negative
      affect due to nicotine content in cigarettes.
AB  - INTRODUCTION: Acute cigarette smoking may relieve withdrawal and negative affect
      due to tobacco abstinence to a greater extent in women versus men. Yet, the
      relative contribution of the cigarette's nicotine content to this sex difference
      is not clear. METHODS: Non-quitting dependent adult smokers (N = 44; 21 males, 23
      females) participated in 2 virtually identical sessions, each after abstaining
      overnight (CO < 10 ppm) and differing only in the nicotine content of the
      designated cigarette. While blind to brand markings, they consumed a total of 24
      puffs in controlled fashion for 2 hr in each session, either from a nicotine
      (Quest 1, 0.6 mg) or denicotinized (Quest 3, 0.05 mg) cigarette. Withdrawal
      symptoms were obtained before and after smoking, and negative affect was assessed
      after each period of cigarette exposure consisting of 6 puffs every 25 min.
      RESULTS: Men and women did not differ in baseline withdrawal and negative affect
      due to overnight abstinence, but reductions in each symptom were significantly
      influenced by the interaction of sex * nicotine/denicotinized cigarette (both p <
      .05). In men, but not in women, each symptom was generally decreased more by the
      nicotine versus denicotinized cigarette, and the nicotine cigarette reduced each
      to a greater degree in men versus women. CONCLUSIONS: Sex differences in relief
      of abstinence-induced withdrawal and negative affect due to the nicotine content
      in cigarettes are consistent with prior research indicating that nicotine per se,
      compared to non-nicotine smoke stimuli, is less rewarding in women versus men.

PMID- 25762755
TI  - Sex differences in time perception during smoking abstinence.
AB  - INTRODUCTION: Nicotine withdrawal leads to impulsive decision-making, which
      reflects a preference for smaller, immediate rewards and often prompts a relapse
      to smoking. The mechanism by which nicotine withdrawal leads to impulsive
      decision-making is not well known. An essential dimension of decision-making is
      time perception. Impulsive decisions reflect intolerance of temporal delays and
      the perception that time is passing more slowly. Sex may be an important factor
      in impulsive decision-making and time perception, but no studies have
      investigated whether sex moderates the effects of nicotine withdrawal on
      impulsive decision-making and time perception. METHODS: Thirty-three (12 female)
      adult smokers completed 2 laboratory sessions: following 24-hr abstinence and
      once smoking-as-usual (order counterbalanced, abstinence biochemically verified).
      Participants completed 2 time perception tasks, a decision-making task, and self
      report measures of craving, withdrawal, and mood. RESULTS: During time
      reproduction, males overestimated time during abstinence compared to smoking,
      whereas there was no session effect for females. On the time discrimination task,
      smokers were less accurate during abstinence, and this effect tended to be
      stronger among females. In general, males had higher discounting rates compared
      with females, but there was no effect of abstinence. CONCLUSIONS: The current
      data suggest that the effect of abstinence on time perception may be stronger in
      males and that males generally exhibit steeper delay discounting rates. Time
      perception may be an important mechanism in smoking abstinence. Our future work
      will investigate the role of time perception in smoking relapse and whether this
      is moderated by sex.

PMID- 25762756
TI  - Financial incentives for smoking cessation among depression-prone pregnant and
      newly postpartum women: effects on smoking abstinence and depression ratings.
AB  - INTRODUCTION: We examined whether pregnant and newly postpartum smokers at risk
      for postpartum depression respond to an incentive-based smoking-cessation
      treatment and how the intervention impacts depression ratings. METHODS: This
      study is a secondary data analysis. Participants (N = 289; data collected 2001
      2013) were smokers at the start of prenatal care who participated in 4 controlled
      clinical trials on the efficacy of financial incentives for smoking cessation.
      Women were assigned either to an intervention wherein they earned vouchers
      exchangeable for retail items contingent on abstaining from smoking or to a
      control condition wherein they received vouchers of comparable value independent
      of smoking status. Treatments were provided antepartum through 12-weeks
      postpartum. Depression ratings (Beck Depression Inventory [BDI]-1A) were examined
      across 7 antepartum/postpartum assessments. Women who reported a history of prior
      depression or who had BDI scores >= 17 at the start of prenatal care were
      categorized as depression-prone (Dep+), while those meeting neither criterion
      were categorized as depression-negative (Dep-). RESULTS: The intervention
      increased smoking abstinence independent of depression status (p < .001), and it
      decreased mean postpartum BDI ratings as well as the proportion of women scoring
      in the clinical range (>=17 and >21) compared with the control treatment (ps <=
      .05). Treatment effects on depression ratings were attributable to changes in
      Dep+ women. CONCLUSIONS: These results demonstrate that depression-prone pregnant
      and newly postpartum women respond well to this incentive-based smoking-cessation
      intervention in terms of achieving abstinence, and the intervention also reduces
      the severity of postpartum depression ratings in this at-risk population.

PMID- 25762758
TI  - Nicotine concentrations with electronic cigarette use: effects of sex and flavor.
AB  - INTRODUCTION: This study examined overall changes in nicotine concentrations when
      using a popular e-cigarette and 18 mg/mL nicotine e-Juice, and it further
      explored effects of sex and flavorings on these concentrations. METHODS: We
      recruited nontreatment-seeking smokers who were willing to try e-cigarettes for 2
      weeks and abstain from cigarette smoking. Subjects were randomized to either
      menthol tobacco or non-menthol tobacco-flavored e-cigarette use for 7-10 days,
      and the next week they were crossed over to the other condition. On the last day
      of e-cigarette use of each flavor, subjects completed a laboratory session in
      which they used the e-cigarette for 5 min ad libitum. Nicotine concentrations
      were obtained 5 min before and 5, 10, 15, 20, and 30 min after the onset of e
      cigarette use. RESULTS: Twenty subjects completed at least 1 monitoring session.
      Nicotine concentrations significantly increased from baseline to 5 min by 4 ng/mL
      at the first laboratory session (p < .01) and by 5.1 ng/mL at the second
      laboratory session (p < .01). Combining sessions, there were no main effects of
      sex or preferred flavor (based on smoking history) on changes in nicotine
      concentrations. After adding preferred flavor, sex, and visit order to the model,
      there was a significant preferred flavor by sex interaction (p < .01), such that
      women who received nonpreferred flavors had lower nicotine concentrations and
      rated their e-cigarette as less likeable (p < .01). CONCLUSION: We found nicotine
      concentrations significantly increase after e-cigarette use for 5 min, and flavor
      may impact nicotine concentrations with e-cigarette use in women.

PMID- 25762757
TI  - Gender differences in medication use and cigarette smoking cessation: results
      from the International Tobacco Control Four Country Survey.
AB  - INTRODUCTION: There is conflicting evidence for gender differences in smoking
      cessation, and there has been little research on gender differences in smoking
      cessation medication (SCM) use and effectiveness. Using longitudinal data from
      the International Tobacco Control Four Country Surveys (ITC-4) conducted in the
      United Kingdom, the United States, Canada, and Australia, we examined gender
      differences in the incidence of quit attempts, reasons for quitting, use of SCMs,
      reasons for discontinuing use of SCMs, and rates of smoking cessation. METHODS:
      Data were analyzed from adult smokers participating in the ITC-4, annual waves
      2006-2011 (n = 7,825), as well as a subsample of smokers (n = 1,079) who made
      quit attempts within 2 months of survey. Adjusted modeling utilized generalized
      estimating equations. RESULTS: There were no gender differences in the likelihood
      of desire to quit, plans to quit, or quit attempts between survey waves. Among
      quit attempters, women had 31% lower odds of successfully quitting (OR = 0.69;
      95% CI = 0.51, 0.94). Stratified by medication use, quit success was lower among
      women who did not use any SCMs (OR = 0.59; 95% CI = 0.39, 0.90), and it was no
      different from men when medications were used (OR = 0.73; 95% CI = 0.46, 1.16).
      In particular, self-selected use of nicotine patch and varenicline contributed to
      successful quitting among women. CONCLUSIONS: Women may have more difficulty
      quitting than men, and SCMs use may help attenuate this difference.

PMID- 25762759
TI  - Gender differences in a randomized controlled trial treating tobacco use among
      adolescents and young adults with mental health concerns.
AB  - INTRODUCTION: Treatment of tobacco use in mental health settings is rare despite
      high rates of comorbidity. With a focus on early intervention, we evaluated a
      tobacco treatment intervention among adolescents and young adults recruited from
      outpatient, school-based, and residential mental health settings and tested for
      gender differences. METHODS: Intervention participants received computerized
      motivational feedback at baseline, 3 months, and 6 months and were offered 12
      weeks of cessation counseling and nicotine patches. Usual care participants
      received a self-help guide and brief cessation advice. We examined 7-day point
      prevalence abstinence with biochemical confirmation at 3, 6, and 12 months;
      smoking reduction; and 24-hr quit attempts. RESULTS: At baseline, the sample (N =
      60, 52% female, mean age = 19.5+/-2.9 years, 40% non-Hispanic Caucasian) averaged
      7+/-6 cigarettes/day, 62% smoked daily, 38% smoked <= 30 min of waking, 12%
      intended to quit in the next month, 47% had a parent who smoked, and 3 of 5 of
      participants' closest friends smoked on average. During the 12-month study, 47%
      of the sample reduced their smoking, 80% quit for 24 hr, and 11%, 13%, and 17%
      confirmed 7-day point prevalence abstinence at 3-, 6-, and 12-month follow-up,
      respectively, with no differences by treatment condition (ps > .400). Over time,
      abstinence was greater among girls (adjusted odds ratio [AOR] = 8.9) than among
      boys, and abstinence was greater for lighter smokers than heavier smokers (AOR =
      4.5) (p < .05). No mental health or other measured variables predicted
      abstinence. CONCLUSIONS: Adolescent and young adult smokers with mental health
      concerns are a challenging group to engage and to effectively treat for tobacco
      addiction, particularly heavier smokers and boys. Innovative approaches are
      needed.

PMID- 25762761
TI  - Protecting children from smoke exposure in disadvantaged homes.
AB  - INTRODUCTION: Smoke-free legislation and shifting norms in many countries have
      reduced secondhand smoke (SHS) exposure, but many children, particularly from
      disadvantaged homes, have high levels of exposure in homes and cars. We explored
      the particular challenges mothers who smoke face when attempting to protect their
      children from SHS exposure in disadvantaged homes. METHODS: We conducted semi
      structured interviews with 22 disadvantaged mothers of children aged 1-3 years in
      Scotland, using an innovative floor plan method to prompt accounts. Interviews
      were analyzed thematically. RESULTS: Disadvantaged mothers reported attempting to
      protect their children from both SHS and becoming smokers, motivated by the
      perceived future health and financial burdens these entail. The variable
      strategies used to protect children during early childhood were constrained
      and/or facilitated by limited and changing living circumstances, single
      parenthood, increasing child mobility and awareness of parental smoking, and
      complex social relationships. In the context of several intersecting dimensions
      of disadvantage (unemployment, low income, alcohol/drug abuse, and domestic
      abuse), the imperative to be and to be seen to be a good mother was also key in
      shaping smoking practices in the home. CONCLUSIONS: Challenging and changing
      domestic living circumstances and relationships and the increasing mobility of
      children in their first few years are key barriers to creating smoke-free homes
      for disadvantaged mothers. Key facilitators include mothers' concerns about
      children's increasing awareness of smoking and moving to accommodation with
      accessible outdoor space. Targeted public health initiatives need to acknowledge
      and support disadvantaged parents' existing motivations and attempts to protect
      children from both SHS and becoming smokers.

PMID- 25762760
TI  - Targeting the noradrenergic system for gender-sensitive medication development
      for tobacco dependence.
AB  - INTRODUCTION: Tobacco use remains the leading cause of morbidity and mortality
      for both women and men in the United States, and women often experience poorer
      smoking cessation outcomes than men. Preliminary evidence suggests there are sex
      differences in medication effectiveness for smoking cessation. However, current
      medications do not take into account gender-sensitive treatment development and
      efficacy, underscoring the importance of this underdeveloped area of research.
      METHODS: We reviewed preclinical and clinical evidence for gender differences in
      the inability to quit smoking by examining (a) the effect of increased negative
      affect and stress reactivity on smoking outcomes in women and (b) smoking for
      nicotine reinforcement in men. We also reviewed the current literature targeting
      the noradrenergic system as a novel gender-sensitive treatment strategy for
      tobacco dependence. RESULTS: We hypothesize that noradrenergic agents that
      normalize noradrenergic activity may differentially attenuate stress reactivity
      in women and nicotine-related reinforcement in men, indicating that targeting the
      noradrenergic system for smoking cessation may be effective for both genders,
      with benefits operating through sex-specific mechanisms. CONCLUSIONS: Converging
      lines of preclinical and clinical evidence suggest that gender-sensitive
      approaches to medication development for smoking cessation are a critical next
      step for addressing low quit rates and exacerbated health risks among women.
      Evidence reviewed indicates that smoking activates different brain systems
      modulated by noradrenergic activity in women versus men, and noradrenergic
      compounds may preferentially target these gender-sensitive systems.

PMID- 25762766
TI  - Multicenter evaluation of Candida QuickFISH BC for identification of Candida
      species directly from blood culture bottles.
AB  - Candida species are common causes of bloodstream infections (BSI), with high
      mortality. Four species cause >90% of Candida BSI: C. albicans, C. glabrata, C.
      parapsilosis, and C. tropicalis. Differentiation of Candida spp. is important
      because of differences in virulence and antimicrobial susceptibility. Candida
      QuickFISH BC, a multicolor, qualitative nucleic acid hybridization assay for the
      identification of C. albicans (green fluorescence), C. glabrata (red
      fluorescence), and C. parapsilosis (yellow fluorescence), was tested on Bactec
      and BacT/Alert blood culture bottles which signaled positive on automated blood
      culture devices and were positive for yeast by Gram stain at seven study sites.
      The results were compared to conventional identification. A total of 419 yeast
      positive blood culture bottles were studied, consisting of 258 clinical samples
      (89 C. glabrata, 79 C. albicans, 23 C. parapsilosis, 18 C. tropicalis, and 49
      other species) and 161 contrived samples inoculated with clinical isolates (40 C.
      glabrata, 46 C. albicans, 36 C. parapsilosis, 19 C. tropicalis, and 20 other
      species). A total of 415 samples contained a single fungal species, with C.
      glabrata (n = 129; 30.8%) being the most common isolate, followed by C. albicans
      (n = 125; 29.8%), C. parapsilosis (n = 59; 14.1%), C. tropicalis (n = 37; 8.8%),
      and C. krusei (n = 17; 4.1%). The overall agreement (with range for the three
      major Candida species) between the two methods was 99.3% (98.3 to 100%), with a
      sensitivity of 99.7% (98.3 to 100%) and a specificity of 98.0% (99.4 to 100%).
      This study showed that Candida QuickFISH BC is a rapid and accurate method for
      identifying C. albicans, C. glabrata, and C. parapsilosis, the three most common
      Candida species causing BSI, directly from blood culture bottles. 

PMID- 25762767
TI  - Subtyping novel zoonotic pathogen Cryptosporidium chipmunk genotype I.
AB  - Cryptosporidium chipmunk genotype I is an emerging zoonotic pathogen in humans.
      The lack of subtyping tools makes it impossible to determine the role of zoonotic
      transmission in epidemiology. To identify potential subtyping markers, we
      sequenced the genome of a human chipmunk genotype I isolate. Altogether,
      9,509,783 bp of assembled sequences in 853 contigs were obtained, with an N50 of
      117,886 bp and >200-fold coverage. Based on the whole-genome sequence data, two
      genetic markers encoding the 60-kDa glycoprotein (gp60) and a mucin protein
      (ortholog of cgd1_470) were selected for the development of a subtyping tool. The
      tool was used for characterizing chipmunk genotype I in 25 human specimens from
      four U.S. states and Sweden, one specimen each from an eastern gray squirrel, a
      chipmunk, and a deer mouse, and 4 water samples from New York. At the gp60 locus,
      although different subtypes were seen among the animals, water, and humans, the
      15 subtypes identified differed mostly in the numbers of trinucleotide repeats
      (TCA, TCG, or TCT) in the serine repeat region, with only two single nucleotide
      polymorphisms in the nonrepeat region. Some geographic differences were found in
      the subtype distribution of chipmunk genotype I from humans. In contrast, only
      two subtypes were found at the mucin locus, which differed from each other in the
      numbers of a 30-bp minisatellite repeat. Thus, Cryptosporidium chipmunk genotype
      I isolates from humans and wildlife are genetically similar, and zoonotic
      transmission might play a potential role in human infections. 

PMID- 25762770
TI  - Point-Counterpoint: Large Multiplex PCR Panels Should Be First-Line Tests for
      Detection of Respiratory and Intestinal Pathogens.
AB  - The first FDA-approved multiplex PCR panel for a large number of respiratory
      pathogens was introduced in 2008. Since then, other PCR panels for detection of
      several respiratory and gastrointestinal pathogens have been approved by the FDA
      and are commercially available, and more such panels are likely to become
      available. These assays detect 12 to 20 pathogens, and some include pathogens
      that typically cause different manifestations of infection, although they infect
      the same organ system. Some of these tests are labor-intensive, while others
      require little labor, and all of them are expensive, both for the laboratory and
      for the patient or insurer. They include a bundle of tests with limited or no
      options for selecting which tests will be performed. Laboratories and hospitals
      have adopted different strategies for offering these assays. Some have
      implemented strategies to limit the use of the tests, such as limiting the
      frequency with which patients can be tested, restricting testing to specific
      groups of patients (e.g., immunocompromised patients), or providing education to
      encourage the use of less expensive tests before using large multiplex panels.
      Others have offered these assays without limiting their use, either relying on
      the ordering provider to exercise good judgment or because such assays are
      thought to be appropriate for first-line diagnostic testing. In this Point
      Counterpoint, Paul Schreckenberger of Loyola University Medical Center explains
      why his laboratory offers these assays without restriction. Alex McAdam of
      Boston's Children Hospital explains the concerns about the use of these assays as
      first-line tests and why some limitations on their use might be appropriate. 

PMID- 25762768
TI  - A novel technique for detecting antibiotic-resistant typhoid from rapid
      diagnostic tests.
AB  - Fluoroquinolone-resistant typhoid is increasing. An antigen-detecting rapid
      diagnostic test (RDT) can rapidly diagnose typhoid from blood cultures. A simple,
      inexpensive molecular technique performed with DNA from positive RDTs accurately
      identified gyrA mutations consistent with phenotypic susceptibility testing
      results. Field diagnosis combined with centralized molecular resistance testing
      could improve typhoid management and surveillance in low-resource settings.

PMID- 25762769
TI  - The Resistant-Population Cutoff (RCOFF): a New Concept for Improved
      Characterization of Antimicrobial Susceptibility Patterns of Non-Wild-Type
      Bacterial Populations.
AB  - This study aimed to determine resistant-population cutoffs (RCOFFs) to allow for
      improved characterization of antimicrobial susceptibility patterns in bacterial
      populations. RCOFFs can complement epidemiological cutoff (ECOFF)-based settings
      of clinical breakpoints (CBPs) by systematically describing the correlation
      between non-wild-type and wild-type populations. We illustrate this concept by
      describing three paradigmatic examples of wild-type and non-wild-type Escherichia
      coli populations from our clinical strain database of disk diffusion diameters.
      The statistical determination of RCOFFs and ECOFFs and their standardized
      applications in antimicrobial susceptibility testing (AST) facilitates the
      assignment of isolates to wild-type or non-wild-type populations. This should
      improve the correlation of in vitro AST data and distinct antibiotic resistance
      mechanisms with clinical outcome facilitating the setting and validation of CBPs.

PMID- 25762771
TI  - An in-house assay is superior to Sepsityper for direct matrix-assisted laser
      desorption ionization-time of flight (MALDI-TOF) mass spectrometry identification
      of yeast species in blood cultures.
AB  - We developed an in-house assay for the direct identification, by matrix-assisted
      laser desorption ionization-time of flight (MALDI-TOF) mass spectrometry, of
      yeasts in blood culture. Sixty-one representative strains from 12 species were
      analyzed in spiked blood cultures. Our assay accurately identified 95 of 107
      (88.8%) positive blood cultures and outperformed the commercial Sepsityper kit
      (81.7% identification). 

PMID- 25762772
TI  - A statistical approach for determination of disk diffusion-based cutoff values
      for systematic characterization of wild-type and non-wild-type bacterial
      populations in antimicrobial susceptibility testing.
AB  - In this study, we introduce a new approach for determination of epidemiologic
      cutoffs (ECOFFs) and resistant-population cutoffs (RCOFFs) based on receiver
      operating characteristic (ROC) curves. As an example, the method was applied for
      determination of ECOFFs for seven different beta-lactam antibiotics and wild-type
      populations of Escherichia coli, Klebsiella pneumoniae, and Enterobacter cloacae.
      In addition, RCOFFs were determined for bacterial populations with defined
      resistance mechanisms ("resistotypes"), i.e., extended-spectrum beta-lactamase
      (ESBL)-positive E. coli, ESBL-positive K. pneumoniae, and ESBL-positive E.
      cloacae; AmpC cephalosporinase-positive E. coli and AmpC-positive K. pneumoniae;
      and broad-spectrum beta-lactamase (BSBL)-positive E. coli. RCOFFs and ECOFFs are
      instrumental for a systematic characterization of associations between
      resistotypes and wild-type populations. 

PMID- 25762773
TI  - Candida inconspicua and Candida norvegensis: new insights into identification in
      relation to sexual reproduction and genome organization.
AB  - Candida inconspicua and Candida (Pichia) norvegensis are two emerging pathogenic
      species that exhibit reduced susceptibility to azole derivatives. Conventional
      (biochemical) approaches do not readily differentiate between the two species.
      The first aim of this work was to analyze the performance of biochemical,
      proteomic (matrix-assisted laser desorption ionization-time of flight [MALDI
      TOF]), and molecular approaches in the precise identification of these species.
      These results then led us to sequence 3 genomic loci, i.e., the internal
      transcribed spacer (ITS) region of the ribosomal DNA (rDNA), the D1/D2 domain of
      the 28S rDNA, and the elongation factor 1alpha (EF-1alpha) gene, either directly
      or following cloning, of 13 clinical isolates and 9 reference strains belonging
      to the 5 species included in the Pichia cactophila clade, namely, Pichia
      cactophila, Pichia insulana, C. inconspicua, C. norvegensis, and P.
      pseudocactophila. Finally, isolates of C. inconspicua were challenged for sexual
      reproduction on the appropriate medium. Our results show that EF-1alpha
      sequencing and proteic profiling by MALDI-TOF are the two most efficient
      approaches to distinguish between C. norvegensis and C. inconspicua. As a
      characteristic of the P. cactophila clade, we found multiple alleles of the rDNA
      regions in certain strains belonging to the tested species, making ITS or D1/D2
      sequencing not appropriate for identification. Whatever the method of
      identification, including MALDI-TOF and EF-1alpha sequencing, none could
      differentiate C. inconspicua from P. cactophila. The results of phylogenetic
      analysis and the generation of asci from pure cultures of all C. inconspicua
      strains both support the identification of P. cactophila as the teleomorph of C.
      inconspicua. 

PMID- 25762774
TI  - Molecular diagnosis of toxoplasmosis in immunocompromised patients: a 3-year
      multicenter retrospective study.
AB  - Toxoplasmosis is a life-threatening infection in immunocompromised patients
      (ICPs). The definitive diagnosis relies on parasite DNA detection, but little is
      known about the incidence and burden of disease in HIV-negative patients. A 3
      year retrospective study was conducted in 15 reference laboratories from the
      network of the French National Reference Center for Toxoplasmosis, in order to
      record the frequency of Toxoplasma gondii DNA detection in ICPs and to review the
      molecular methods used for diagnosis and the prevention measures implemented in
      transplant patients. During the study period, of 31,640 PCRs performed on samples
      from ICPs, 610 were positive (323 patients). Blood (n = 337 samples),
      cerebrospinal fluid (n = 101 samples), and aqueous humor (n = 100 samples) were
      more frequently positive. Chemoprophylaxis schemes in transplant patients
      differed between centers. PCR follow-up of allogeneic hematopoietic stem cell
      transplant (allo-HSCT) patients was implemented in 8/15 centers. Data from 180
      patients (13 centers) were further analyzed regarding clinical setting and
      outcome. Only 68/180 (38%) patients were HIV(+); the remaining 62% consisted of
      72 HSCT, 14 solid organ transplant, and 26 miscellaneous immunodeficiency
      patients. Cerebral toxoplasmosis and disseminated toxoplasmosis were most
      frequently observed in HIV and transplant patients, respectively. Of 72 allo-HSCT
      patients with a positive PCR result, 23 were asymptomatic; all were diagnosed in
      centers performing systematic blood PCR follow-up, and they received specific
      treatment. Overall survival of allo-HSCT patients at 2 months was better in
      centers with PCR follow-up than in other centers (P < 0.01). This study provides
      updated data on the frequency of toxoplasmosis in HIV-negative ICPs and suggests
      that regular PCR follow-up of allo-HSCT patients could guide preemptive treatment
      and improve outcome. 

PMID- 25762775
TI  - Fever in a visitor to Canada: a case of mistaken identity.
AB  - We report a case of babesiosis in a traveler from India who was diagnosed with
      malaria on the basis of blood smears. Pan-Plasmodium PCR was positive, though
      species-specific assays were negative. Reexamination of blood smears and Babesia
      specific PCR confirmed babesiosis. We highlight the overlapping clinical and
      diagnostic features of malaria and babesiosis and the potential cross-reactivity
      of Plasmodium primers in cases of babesiosis. 

PMID- 25762776
TI  - Salmonella serotype determination utilizing high-throughput genome sequencing
      data.
AB  - Serotyping forms the basis of national and international surveillance networks
      for Salmonella, one of the most prevalent foodborne pathogens worldwide (1-3).
      Public health microbiology is currently being transformed by whole-genome
      sequencing (WGS), which opens the door to serotype determination using WGS data.
      SeqSero (www.denglab.info/SeqSero) is a novel Web-based tool for determining
      Salmonella serotypes using high-throughput genome sequencing data. SeqSero is
      based on curated databases of Salmonella serotype determinants (rfb gene cluster,
      fliC and fljB alleles) and is predicted to determine serotype rapidly and
      accurately for nearly the full spectrum of Salmonella serotypes (more than 2,300
      serotypes), from both raw sequencing reads and genome assemblies. The performance
      of SeqSero was evaluated by testing (i) raw reads from genomes of 308 Salmonella
      isolates of known serotype; (ii) raw reads from genomes of 3,306 Salmonella
      isolates sequenced and made publicly available by GenomeTrakr, a U.S. national
      monitoring network operated by the Food and Drug Administration; and (iii) 354
      other publicly available draft or complete Salmonella genomes. We also
      demonstrated Salmonella serotype determination from raw sequencing reads of fecal
      metagenomes from mice orally infected with this pathogen. SeqSero can help to
      maintain the well-established utility of Salmonella serotyping when integrated
      into a platform of WGS-based pathogen subtyping and characterization. 

PMID- 25762777
TI  - Genetic Diversity of White Sharks, Carcharodon carcharias, in the Northwest
      Atlantic and Southern Africa.
AB  - The white shark, Carcharodon carcharias, is both one of the largest apex
      predators in the world and among the most heavily protected marine fish.
      Population genetic diversity is in part shaped by recent demographic history and
      can thus provide information complementary to more traditional population
      assessments, which are difficult to obtain for white sharks and have at times
      been controversial. Here, we use the mitochondrial control region and 14 nuclear
      encoded microsatellite loci to assess white shark genetic diversity in 2 regions:
      the Northwest Atlantic (NWA, N = 35) and southern Africa (SA, N = 131). We find
      that these 2 regions harbor genetically distinct white shark populations (Phi ST
      = 0.10, P < 0.00001; microsatellite F ST = 0.1057, P < 0.021). M-ratios were low
      and indicative of a genetic bottleneck in the NWA (M-ratio = 0.71, P < 0.004) but
      not SA (M-ratio = 0.85, P = 0.39). This is consistent with other evidence showing
      a steep population decline occurring in the mid to late 20th century in the NWA,
      whereas the SA population appears to have been relatively stable. Estimates of
      effective population size ranged from 22.6 to 66.3 (NWA) and 188 to 1998.3 (SA)
      and evidence of inbreeding was found (primarily in NWA). Overall, our findings
      indicate that white population dynamics within NWA and SA are determined more by
      intrinsic reproduction than immigration and there is genetic evidence of a
      population decline in the NWA, further justifying the strong domestic protective
      measures that have been taken for this species in this region. Our study also
      highlights how assessment of genetic diversity can complement other sources of
      information to better understand the status of threatened marine fish
      populations. 

PMID- 25762779
TI  - Deletion of receptor for advanced glycation end products exacerbates
      lymphoproliferative syndrome and lupus nephritis in B6-MRL Fas lpr/j mice.
AB  - The receptor for advanced glycation end products (RAGE) is a pattern recognition
      receptor that interacts with advanced glycation end products, but also with C3a,
      CpG DNA oligonucleotides, and alarmin molecules such as HMGB1 to initiate a
      proinflammatory reaction. Systemic lupus erythematosus is an autoimmune disorder
      associated with the accumulation of RAGE ligands. We generated mice invalidated
      for RAGE in the lupus-prone B6-MRL Fas lpr/j background to determine the role of
      RAGE in the pathogenesis of systemic lupus erythematosus. We compared the
      phenotype of these mice with that of their wild-type and B6-MRL Fas lpr/j
      littermates. Lymphoproliferative syndrome, production of anti-dsDNA Abs, lupus
      nephritis, and accumulation of CD3(+)B220(+)CD4(-)CD8(-) autoreactive T cells (in
      the peripheral blood and the spleen) were significantly increased in B6-MRL Fas
      lpr/j RAGE(-/-) mice compared with B6-MRL Fas lpr/j mice (respectively p < 0.005,
      p < 0.05, p < 0.001, and p < 0.001). A large proportion of autoreactive T cells
      from B6-MRL Fas lpr/j mice expressed RAGE at their surface. Time course studies
      of annexin V expression revealed that autoreactive T cells in the spleen of B6
      MRL Fas lpr/j-RAGE(-/-) mice exhibited a delay in apoptosis and expressed
      significantly less activated caspase 3 (39.5 +/- 4.3%) than T cells in B6-MRL Fas
      lpr/j mice (65.5 +/- 5.2%) or wild-type mice (75.3 +/- 2.64%) (p = 0.02). We
      conclude that the deletion of RAGE in B6-MRL Fas lpr/j mice promotes the
      accumulation of autoreactive CD3(+)B220(+)CD4(-)CD8(-) T cells, therefore
      exacerbating lymphoproliferative syndrome, autoimmunity, and organ injury. This
      suggests that RAGE rescues the apoptosis of T lymphocytes when the death receptor
      Fas/CD95 is dysfunctional. 

PMID- 25762778
TI  - K+ efflux agonists induce NLRP3 inflammasome activation independently of Ca2+
      signaling.
AB  - Perturbation of intracellular ion homeostasis is a major cellular stress signal
      for activation of NLRP3 inflammasome signaling that results in caspase-1-mediated
      production of IL-1beta and pyroptosis. However, the relative contributions of
      decreased cytosolic K(+) concentration versus increased cytosolic Ca(2+)
      concentration ([Ca(2+)]) remain disputed and incompletely defined. We
      investigated roles for elevated cytosolic [Ca(2+)] in NLRP3 activation and
      downstream inflammasome signaling responses in primary murine dendritic cells and
      macrophages in response to two canonical NLRP3 agonists (ATP and nigericin) that
      facilitate primary K(+) efflux by mechanistically distinct pathways or the
      lysosome-destabilizing agonist Leu-Leu-O-methyl ester. The study provides three
      major findings relevant to this unresolved area of NLRP3 regulation. First,
      increased cytosolic [Ca(2+)] was neither a necessary nor sufficient signal for
      the NLRP3 inflammasome cascade during activation by endogenous ATP-gated P2X7
      receptor channels, the exogenous bacterial ionophore nigericin, or the
      lysosomotropic agent Leu-Leu-O-methyl ester. Second, agonists for three Ca(2+)
      mobilizing G protein-coupled receptors (formyl peptide receptor, P2Y2 purinergic
      receptor, and calcium-sensing receptor) expressed in murine dendritic cells were
      ineffective as activators of rapidly induced NLRP3 signaling when directly
      compared with the K(+) efflux agonists. Third, the intracellular Ca(2+) buffer,
      BAPTA, and the channel blocker, 2-aminoethoxydiphenyl borate, widely used
      reagents for disruption of Ca(2+)-dependent signaling pathways, strongly
      suppressed nigericin-induced NLRP3 inflammasome signaling via mechanisms
      dissociated from their canonical or expected effects on Ca(2+) homeostasis. The
      results indicate that the ability of K(+) efflux agonists to activate NLRP3
      inflammasome signaling can be dissociated from changes in cytosolic [Ca(2+)] as a
      necessary or sufficient signal. 

PMID- 25762780
TI  - HkRP3 is a microtubule-binding protein regulating lytic granule clustering and NK
      cell killing.
AB  - NK cells provide host defense by killing viral-infected and cancerous cells
      through the secretion of preformed lytic granules. Polarization of the lytic
      granules toward the target cell is dependent on an intact microtubule (MT)
      network as well as MT motors. We have recently shown that DOCK8, a gene mutated
      in a primary immunodeficiency syndrome, is involved in NK cell killing in part
      through its effects on MT organizing center (MTOC) polarization. In this study,
      we identified Hook-related protein 3 (HkRP3) as a novel DOCK8- and MT-binding
      protein. We further show that HkRP3 is present in lytic granule fractions and
      interacts with the dynein motor complex and MTs. Significantly, depletion of
      HkPR3 impaired NK cell cytotoxicity, which could be attributed to a defect in not
      only MTOC polarity, but also impaired clustering of lytic granules around the
      MTOC. Our results demonstrate an important role for HkRP3 in regulating the
      clustering of lytic granules and MTOC repositioning during the development of NK
      cell-mediated killing. 

PMID- 25762781
TI  - IL-12 promotes myeloid-derived suppressor cell recruitment and bacterial
      persistence during Staphylococcus aureus orthopedic implant infection.
AB  - Staphylococcus aureus is a leading cause of human prosthetic joint infections
      (PJIs) typified by biofilm formation. We recently identified a critical role for
      myeloid-derived suppressor cells (MDSCs) in S. aureus biofilm persistence.
      Proinflammatory signals induce MDSC recruitment and activation in tumor models;
      however, the mechanisms responsible for MDSC homing to sites of biofilm infection
      are unknown. In this study, we report that several cytokines (IL-12p40, IL-1beta,
      TNF-alpha, and G-CSF) and chemokines (CXCL2, CCL5) were significantly elevated in
      a mouse model of S. aureus PJI. This coincided with significantly increased MDSC
      infiltrates concomitant with reduced monocyte, macrophage, and T cell influx
      compared with uninfected animals. Of the cytokines detected, IL-12 was of
      particular interest based on its ability to possess either pro- or anti
      inflammatory effects mediated through p35-p40 heterodimers or p40 homodimers,
      respectively. MDSC recruitment was significantly reduced in both p40 and p35
      knockout mice, which resulted in enhanced monocyte and neutrophil influx and
      bacterial clearance. Adoptive transfer of wild-type MDSCs into infected p40
      knockout animals worsened disease outcome, as evidenced by the return of S.
      aureus burdens to levels typical of wild-type mice. Tissues obtained from
      patients undergoing revision surgery for PJI revealed similar patterns of immune
      cell influx, with increased MDSC-like cells and significantly fewer T cells
      compared with aseptic revisions. These findings reveal a critical role for IL-12
      in shaping the anti-inflammatory biofilm milieu by promoting MDSC recruitment. 

PMID- 25762782
TI  - Deficiency of MALT1 paracaspase activity results in unbalanced regulatory and
      effector T and B cell responses leading to multiorgan inflammation.
AB  - The paracaspase MALT1 plays an important role in immune receptor-driven signaling
      pathways leading to NF-kappaB activation. MALT1 promotes signaling by acting as a
      scaffold, recruiting downstream signaling proteins, as well as by proteolytic
      cleavage of multiple substrates. However, the relative contributions of these two
      different activities to T and B cell function are not well understood. To
      investigate how MALT1 proteolytic activity contributes to overall immune cell
      regulation, we generated MALT1 protease-deficient mice (Malt1(PD/PD)) and
      compared their phenotype with that of MALT1 knockout animals (Malt1(-/-)).
      Malt1(PD/PD) mice displayed defects in multiple cell types including marginal
      zone B cells, B1 B cells, IL-10-producing B cells, regulatory T cells, and mature
      T and B cells. In general, immune defects were more pronounced in Malt1(-/-)
      animals. Both mouse lines showed abrogated B cell responses upon immunization
      with T-dependent and T-independent Ags. In vitro, inactivation of MALT1 protease
      activity caused reduced stimulation-induced T cell proliferation, impaired IL-2
      and TNF-alpha production, as well as defective Th17 differentiation.
      Consequently, Malt1(PD/PD) mice were protected in a Th17-dependent experimental
      autoimmune encephalomyelitis model. Surprisingly, Malt1(PD/PD) animals developed
      a multiorgan inflammatory pathology, characterized by Th1 and Th2/0 responses and
      enhanced IgG1 and IgE levels, which was delayed by wild-type regulatory T cell
      reconstitution. We therefore propose that the pathology characterizing
      Malt1(PD/PD) animals arises from an immune imbalance featuring pathogenic Th1-
      and Th2/0-skewed effector responses and reduced immunosuppressive compartments.
      These data uncover a previously unappreciated key function of MALT1 protease
      activity in immune homeostasis and underline its relevance in human health and
      disease. 

PMID- 25762783
TI  - DAP12 expression in lung macrophages mediates ischemia/reperfusion injury by
      promoting neutrophil extravasation.
AB  - Neutrophils are critical mediators of innate immune responses and contribute to
      tissue injury. However, immune pathways that regulate neutrophil recruitment to
      injured tissues during noninfectious inflammation remain poorly understood. DAP12
      is a cell membrane-associated protein that is expressed in myeloid cells and can
      either augment or dampen innate inflammatory responses during infections. To
      elucidate the role of DAP12 in pulmonary ischemia/reperfusion injury (IRI), we
      took advantage of a clinically relevant mouse model of transplant-mediated lung
      IRI. This technique allowed us to dissect the importance of DAP12 in tissue
      resident cells and those that infiltrate injured tissue from the periphery during
      noninfectious inflammation. Macrophages in both mouse and human lungs that have
      been subjected to cold ischemic storage express DAP12. We found that donor, but
      not recipient, deficiency in DAP12 protected against pulmonary IRI. Analysis of
      the immune response showed that DAP12 promotes the survival of tissue-resident
      alveolar macrophages and contributes to local production of neutrophil
      chemoattractants. Intravital imaging demonstrated a transendothelial migration
      defect into DAP12-deficient lungs, which can be rescued by local administration
      of the neutrophil chemokine CXCL2. We have uncovered a previously unrecognized
      role for DAP12 expression in tissue-resident alveolar macrophages in mediating
      acute noninfectious tissue injury through regulation of neutrophil trafficking. 

PMID- 25762784
TI  - NF-kappaB downregulates Cbl-b through binding and suppressing Cbl-b promoter in T
      cell activation.
AB  - T cell activation causes the translocation of NF-kappaB dimers from the cytoplasm
      into the nucleus where NF-kappaB regulates inflammatory and immune response
      genes. Cbl-b is a negative regulator of T cell activation. However, the
      correlation between NF-kappaB activity and Cbl-b expression remains unclear. We
      showed that IkappaBalphaDeltaN-Tg T cells exhibited less NF-kappaB activity but
      higher levels of Cbl-b when compared with wild-type T cells. Furthermore, ursolic
      acid suppressed NF-kappaB activation and inhibited the downregulation of Cbl-b in
      wild-type T cells. NF-kappaBp65 specifically bound to an 11-bp NF-kappaB
      consensus sequence (gcaggaagtcc) in the Cbl-b promoter. Binding of NF-kappaB to
      this sequence suppressed Cbl-b transcription, thereby resulting in the negative
      regulation of Cbl-b expression. In addition, Cbl-b knockout led to the loss of
      cardiac allograft tolerance in IkappaBalphaDeltaN-Tg mice. These results
      indicated that NF-kappaB downregulated Cbl-b by binding and suppressing Cbl-b
      promoter in T cell activation. Our findings provide a novel role for NF-kappaB
      signaling in T cell activation. 

PMID- 25762786
TI  - Increased Thrombopoiesis and Platelet Activation in Hantavirus-Infected Patients.
AB  - BACKGROUND: Thrombocytopenia is a common finding during viral hemorrhagic fever,
      which includes hemorrhagic fever with renal syndrome (HFRS). The 2 main causes
      for thrombocytopenia are impaired thrombopoiesis and/or increased peripheral
      destruction of platelets. In addition, there is an increased intravascular
      coagulation risk during HFRS, which could be due to platelet activation. METHODS:
      Thrombopoiesis was determined by quantification of platelet counts,
      thrombopoietin, immature platelet fraction, and mean platelet volume during HFRS.
      The in vivo platelet activation was determined by quantification of soluble P
      selectin (sP-selectin) and glycoprotein VI (sGPVI). The function of circulating
      platelets was determined by ex vivo stimulation followed by flow cytometry
      analysis of platelet surface-bound fibrinogen and P-selectin exposure.
      Intravascular coagulation during disease was determined by scoring for
      disseminated intravascular coagulation (DIC) and recording thromboembolic
      complications. RESULTS: The levels of thrombopoietin, immature platelet fraction,
      and mean platelet volume all indicate increased thrombopoiesis during HFRS.
      Circulating platelets had reduced ex vivo function during disease compared to
      follow-up. Most interestingly, we observed significantly increased in vivo
      platelet activation in HFRS patients with intravascular coagulation (DIC and
      thromboembolic complications) as shown by sP-selectin and sGPVI levels.
      CONCLUSIONS: HFRS patients have increased thrombopoiesis and platelet activation,
      which contributes to intravascular coagulation.

PMID- 25762785
TI  - Coexpression of TIGIT and FCRL3 identifies Helios+ human memory regulatory T
      cells.
AB  - Two distinct subsets of CD4(+)Foxp3(+) regulatory T (Treg) cells have been
      described based on the differential expression of Helios, a transcription factor
      of the Ikaros family. Efforts to understand the origin and biological roles of
      these Treg populations in regulating immune responses have, however, been
      hindered by the lack of reliable surface markers to distinguish and isolate them
      for subsequent functional studies. Using a single-cell cloning strategy coupled
      with microarray analysis of different Treg functional subsets in humans, we
      identify the mRNA and protein expression of TIGIT and FCRL3 as a novel surface
      marker combination that distinguishes Helios(+)FOXP3(+) from Helios(-)FOXP3(+)
      memory cells. Unlike conventional markers that are modulated on conventional T
      cells upon activation, we show that the TIGIT/FCRL3 combination allows reliable
      identification of Helios(+) Treg cells even in highly activated conditions in
      vitro as well as in PBMCs of autoimmune patients. We also demonstrate that the
      Helios(-)FOXP3(+) Treg subpopulation harbors a larger proportion of
      nonsuppressive clones compared with the Helios(+)FOXP3(+) cell subset, which is
      highly enriched for suppressive clones. Moreover, we find that Helios(-) cells
      are exclusively responsible for the productions of the inflammatory cytokines IFN
      gamma, IL-2, and IL-17 in FOXP3(+) cells ex vivo, highlighting important
      functional differences between Helios(+) and Helios(-) Treg cells. Thus, we
      identify novel surface markers for the consistent identification and isolation of
      Helios(+) and Helios(-) memory Treg cells in health and disease, and we further
      reveal functional differences between these two populations. These new markers
      should facilitate further elucidation of the functional roles of Helios-based
      Treg heterogeneity. 

PMID- 25762787
TI  - Transcriptional Adaptation of Drug-tolerant Mycobacterium tuberculosis During
      Treatment of Human Tuberculosis.
AB  - BACKGROUND: Treatment initiation rapidly kills most drug-susceptible
      Mycobacterium tuberculosis, but a bacterial subpopulation tolerates prolonged
      drug exposure. We evaluated drug-tolerant bacilli in human sputum by comparing
      messenger RNA (mRNA) expression of drug-tolerant bacilli that survive the early
      bactericidal phase with treatment-naive bacilli. METHODS: M. tuberculosis gene
      expression was quantified via reverse-transcription polymerase chain reaction in
      serial sputa from 17 Ugandans treated for drug-susceptible pulmonary
      tuberculosis. RESULTS: Within 4 days, bacterial mRNA abundance declined >98%,
      indicating rapid killing. Thereafter, the rate of decline slowed >94%, indicating
      drug tolerance. After 14 days, 16S ribosomal RNA transcripts/genome declined 96%,
      indicating slow growth. Drug-tolerant bacilli displayed marked downregulation of
      genes associated with growth, metabolism, and lipid synthesis and upregulation in
      stress responses and key regulatory categories-including stress-associated sigma
      factors, transcription factors, and toxin-antitoxin genes. Drug efflux pumps were
      upregulated. The isoniazid stress signature was induced by initial drug exposure,
      then disappeared after 4 days. CONCLUSIONS: Transcriptional patterns suggest that
      drug-tolerant bacilli in sputum are in a slow-growing, metabolically and
      synthetically downregulated state. Absence of the isoniazid stress signature in
      drug-tolerant bacilli indicates that physiological state influences drug
      responsiveness in vivo. These results identify novel drug targets that should aid
      in development of novel shorter tuberculosis treatment regimens.

PMID- 25762788
TI  - Kidney Dysfunction and Markers of Inflammation in the Multicenter AIDS Cohort
      Study.
AB  - BACKGROUND: Human immunodeficiency virus (HIV)-infected individuals are at higher
      risk for chronic kidney disease than HIV-uninfected individuals. We investigated
      whether the inflammation present in treated HIV infection contributes to kidney
      dysfunction among HIV-infected men receiving highly active antiretroviral
      therapy. METHODS: The glomerular filtration rate (GFR) was directly measured
      (using iohexol) along with 12 markers of inflammation in Multicenter AIDS Cohort
      Study participants. Exploratory factor analysis was used to identify inflammatory
      processes related to kidney dysfunction. The estimated levels of these
      inflammatory processes were used in adjusted logistic regression analyses
      evaluating cross-sectional associations with kidney function outcomes. RESULTS:
      There were 434 HIV-infected men receiving highly active antiretroviral therapy
      and 200 HIV-uninfected men. HIV-infected men were younger (median age, 51 vs 53
      years) and had higher urine protein-creatinine ratios (median, 98 vs 66 mg/g) but
      comparable GFRs (median, 109 vs 106 mL/min|1.73 m(2)). We found an inflammatory
      process dominated by markers: soluble tumor necrosis factor receptor 2, soluble
      interleukin 2 receptor alpha, soluble gp130, soluble CD27, and soluble CD14. An
      increase of 1 standard deviation in that inflammatory process was associated with
      significantly greater odds of GFR <=90 mL/min/1.73 m(2) (odds ratio, 2.0) and
      urine protein >200 mg/g (odds ratio, 2.3). CONCLUSIONS: Higher circulating levels
      of immune activation markers among treated HIV-infected men may partially explain
      their higher burden of kidney dysfunction compared with uninfected men.

PMID- 25762789
TI  - Antibody Response is More Likely to Pneumococcal Proteins Than to Polysaccharide
      After HIV-associated Invasive Pneumococcal Disease.
AB  - BACKGROUND: Human immunodeficiency virus (HIV)-infected individuals are at
      increased risk of invasive pneumococcal disease (IPD). In order to assess the
      immunogenicity of pneumococcal proteins and polysaccharide, we investigated
      protein and serotype-specific antibody responses after HIV-associated IPD.
      METHODS: Specific antipneumococcal immunoglobulin G to 27 pneumococcal protein
      antigens and 30 serotype polysaccharides was measured in plasma before and after
      IPD in HIV-infected individuals and compared to HIV-infected individuals without
      IPD. RESULTS: Over time, 81% of IPD cases responded to at least 1 protein
      compared to 51% of non-IPD controls. HIV IPD cases responded to more proteins
      than non-IPD controls (8.6 +/- 8.4 vs 4.2 +/- 7.6 proteins; P = .01), and had a
      significantly higher probability of yielding an antibody response to the proteins
      PiaA, PsaA, and PcpA. Twenty-two percent of HIV-infected individuals with IPD had
      a serotype-specific antibody response. Younger age at the time of IPD was the
      only predictor of a serotype-specific pneumococcal antibody response, whereas we
      did not identify predictors of a protein-specific antibody response. CONCLUSIONS:
      Antibody responses occurred more frequently to pneumococcal proteins than to
      polysaccharide, and protein antibodies persisted for longer than polysaccharide
      specific antibodies. PcpA, PiaA, and PsaA were the most immunogenic proteins.

PMID- 25762790
TI  - Phylogenetic and Geographic Relationships of Severe Fever With Thrombocytopenia
      Syndrome Virus in China, South Korea, and Japan.
AB  - BACKGROUND: Severe fever with thrombocytopenia syndrome (SFTS) is a tick-borne
      acute infectious disease caused by the SFTS virus (SFTSV). SFTS has been reported
      in China, South Korea, and Japan as a novel Bunyavirus. Although several
      molecular epidemiology and phylogenetic studies have been performed, the
      information obtained was limited, because the analyses included no or only a
      small number of SFTSV strains from Japan. METHODS: The nucleotide sequences of 75
      SFTSV samples in Japan were newly determined directly from the patients' serum
      samples. In addition, the sequences of 7 strains isolated in vitro were
      determined and compared with those in the patients' serum samples. More than 90
      strains that were identified in China, 1 strain in South Korea, and 50 strains in
      Japan were phylogenetically analyzed. RESULTS: The viruses were clustered into 2
      clades, which were consistent with the geographic distribution. Three strains
      identified in Japan were clustered in the Chinese clade, and 4 strains identified
      in China and 26 in South Korea were clustered in the Japanese clade. CONCLUSIONS:
      Two clades of SFTSV may have evolved separately over time. On rare occasions, the
      viruses were transmitted overseas to the region in which viruses of the other
      clade were prevalent.

PMID- 25762792
TI  - Adequate design of pharmacokinetic-pharmacodynamic studies will help optimize
      tuberculosis treatment for the future.

PMID- 25762791
TI  - Proteolytic Cleavage of the Plasmodium falciparum Circumsporozoite Protein Is a
      Target of Protective Antibodies.
AB  - Studies in animals and human volunteers demonstrate that antibodies against the
      repeat-region of the Plasmodium circumsporozoite protein (CSP) abrogate
      sporozoite infection. However, the realization that the N- and C- terminal
      regions flanking the repeats play essential roles in parasite infectivity raised
      the possibility that they could be targeted by protective antibodies. We
      characterized a monoclonal antibody (mAb5D5) specific for the N-terminus of the
      P. falciparum CSP, which inhibits the proteolytic cleavage of the CSP, a key
      requirement for parasite infection of hepatocytes. Adoptive transfer of mAb5D5
      strongly inhibits the in vivo infection of sporozoites expressing the N-terminus
      of P. falciparum CSP, and this protection is greatly enhanced when combined with
      antirepeat antibodies. Our results show that antibodies interfering with
      molecular processes required for parasite infectivity can exert a strong in vivo
      protective activity and indicate that pre-erythrocytic vaccines against
      Plasmodium should include the CSP N-terminal region. 

PMID- 25762793
TI  - Reply to "adequate design of pharmacokinetic-pharmacodynamic studies will help
      optimize tuberculosis treatment for the future".

PMID- 25762794
TI  - Nomenclature and functionality of the so-called cfr gene from Clostridium
      difficile.

PMID- 25762795
TI  - Erratum for Kim et al., inappropriate continued empirical vancomycin use in a
      hospital with a high prevalence of methicillin-resistant Staphylococcus aureus.

PMID- 25762797
TI  - Purification and characterization of a salt-tolerant cellulase from the mangrove
      oyster, Crassostrea rivularis.
AB  - A cellulase with wide range of pH resistance and high salt tolerance was isolated
      from the digestive gland of the oyster Crassostrea rivularis living in mangrove
      forests. The 27 kDa cellulase named as CrCel was purified 40.6 folds by anion
      exchange chromatography and extraction from the gel after non-reducing sodium
      dodecylsufate-polyacrylamide gel electrophoresis. The specific activity of the
      purified cellulase was 23.4 U/mg against carboxymethyl cellulose (CMC). The N
      terminal amino acid sequence of CrCel was determined to be NQKCQANSRV. CrCel
      preferably hydrolyzes beta-1,4-glucosidic bonds in the amorphous parts of
      cellulose materials and displays degradation activity toward xylan. The Km and
      Vmax values of CrCel for CMC were determined to be 2.1% +/- 0.4% and 73.5 +/- 3.3
      U mg(-1), respectively. The optimal pH value and temperature of CrCel were 5.5
      and 40 degrees C, respectively. The enzyme was stable in a wide range of pH,
      retaining over 60% activity after incubation for 80 min in the pH range of 3.0
      9.0. In addition, CrCel showed remarkable tolerance to salt and remained active
      at high NaCl concentrations, but also retained over 70% activity after incubation
      in 0.5-2 M NaCl for up to 24 h. On the basis of the N-terminal sequence alignment
      and its similar properties to other animal cellulases, CrCel was regarded as a
      member of glycosyl hydrolase family 45 beta-1,4-glucanases. CrCel is the first
      reported cellulase isolated from mangrove invertebrates, which suggests that it
      may participate in the assimilation of cellulolytic materials derived from the
      food sources of the oyster and contribute to the consumption of mangrove primary
      production. The unique properties of this enzyme make it a potential candidate
      for further industrial application.

PMID- 25762798
TI  - Recent progress and future direction of cancer epidemiological research in Japan.
AB  - In 2006, the Cancer Control Act was approved and a Basic Plan, to Promote the
      Cancer Control Program at the national level, was developed in 2007. Cancer
      research is recognized as a fundamental component to provide evidence in cancer
      control program. Cancer epidemiology plays central role in connecting research
      and policy, since it directly deals with data from humans. Research for cancer
      epidemiology in Japan made substantial progress, in the field of descriptive
      studies, cohort studies, intervention studies and activities for summarizing
      evidences. In future, promoting high-quality large-scale intervention studies,
      individual-level linkage studies, simulation models and studies for elderly
      population will be of great importance, but at the same time research should be
      promoted in well-balanced fashion not placing too much emphasis on one particular
      research field. 

PMID- 25762799
TI  - Personality traits and coping styles explain anxiety in lung cancer patients to a
      greater extent than other factors.
AB  - OBJECTIVE: Although various factors thought to be correlated with anxiety in
      cancer patients, relative importance of each factors were unknown. We tested our
      hypothesis that personality traits and coping styles explain anxiety in lung
      cancer patients to a greater extent than other factors. METHODS: A total of 1334
      consecutively recruited lung cancer patients were selected, and data on cancer
      related variables, demographic characteristics, health behaviors, physical
      symptoms and psychological factors consisting of personality traits and coping
      styles were obtained. The participants were divided into groups with or without a
      significant anxiety using the Hospital Anxiety and Depression Scale-Anxiety, and
      a binary logistic regression analysis was used to identify factors correlated
      with significant anxiety using a multivariate model. RESULTS: Among the recruited
      patients, 440 (33.0%) had significant anxiety. The binary logistic regression
      analysis revealed a coefficient of determination (overall R(2)) of 39.0%, and the
      explanation for psychological factors was much higher (30.7%) than those for
      cancer-related variables (1.1%), demographic characteristics (2.1%), health
      behaviors (0.8%) and physical symptoms (4.3%). Four specific factors remained
      significant in a multivariate model. A neurotic personality trait, a coping style
      of helplessness/hopelessness, and a female sex were positively correlated with
      significant anxiety, while a coping style of fatalism was negatively correlated.
      CONCLUSIONS: Our hypothesis was supported, and anxiety was strongly linked with
      personality trait and coping style. As a clinical implication, the use of
      screening instruments to identify these factors and intervention for
      psychological crisis may be needed.

PMID- 25762800
TI  - Fund of Information is More Strongly Associated with Neuropsychological
      Functioning Than Education in Older Spanish Adults.
AB  - Educational influence on cognitive performance has been extensively agreed in
      Neuropsychology. Nonetheless, recent studies highlighted the need of better
      measurements to assess benefit from the schooling experience in order to further
      understand schooling influence on cognition. The WAIS-III Information subtest is
      proposed here to measure this influence at old age. Ninety-five older adults were
      divided according to their educational attainment and their Information subtest
      score, and completed extensive neuropsychological assessment. Performance on the
      Information subtest had a significant effect on all same cognitive functions as
      educational attainment, but also on additional domains. Moreover, cognitive
      performance on several tasks can be classified in three levels as a function of
      Information score. The WAIS-III Information subtest could be of special interest
      as a measurement of the benefit from educational experience not only to study
      cognition in Spanish older populations but also heterogeneous samples in terms of
      educational experiences and environments. 

PMID- 25762801
TI  - The integration of Korean medicine in South Korea.

PMID- 25762802
TI  - The health of older arrestees in police cells.
AB  - BACKGROUND: detention in the harsh conditions of police cells can be a traumatic
      experience, even for young healthy individuals. It is thus legitimate to question
      the detention of elderly people. OBJECTIVE: we aimed to determine the proportion
      of detainees over age 60, their medical characteristics and history. METHODS: we
      studied all arrestees over age 60 examined in 1 year (1st January-31 December
      2012) by physicians from our Department of Forensic Medicine in the Paris, France
      area. Our analysis included the arrestees' perceived health status and their
      opinion on custody. RESULTS: individuals over 60 accounted for 211 of 13,317
      detainees (2%) and were predominantly males (177 of 211, 84%). The most frequent
      suspected crimes included physical assaults (135 of 345, 40%) and drunk driving
      (50 of 345, 14%). A total of 111 of 211 individuals (53%) reported somatic
      disorders. A history of psychiatric disorders was reported by 23 of 181
      individuals (13%). Arrestees considered their overall health as good in 60% of
      cases (111 of 184). They had a good opinion on custody in 45% of cases (120 of
      270). A proportion of 40% (84 of 211) were examined several times during custody
      and 10% were declared unfit for custody (34 of 347). CONCLUSIONS: elderly
      detainees commonly have chronic health disorders; only a minority of them are
      unconditionally fit for detention. The continuation of detention, which affects
      90% of arrestees, should imply that detention conditions are adjusted so that the
      specific needs of elderly individuals are taken into account.

PMID- 25762804
TI  - QRS fragmentation and sudden cardiac death in the obese and overweight.
AB  - BACKGROUND: Obesity has been associated with significantly greater risk of sudden
      cardiac death (SCD); however, identifying the obese patient at highest risk
      remains a challenge. We evaluated the association between QRS fragmentation on
      the 12-lead electrocardiogram and SCD, in obese/overweight subjects. METHODS AND
      RESULTS: In the ongoing prospective, community-based Oregon Sudden Unexpected
      Death Study (population approximately 1 million), we performed a case-control
      analysis, comparing obese/overweight SCD victims with obese/overweight controls
      from the same geographic region. Archived ECGs prior and unrelated to the SCD
      event were used for cases and all ECG measurements were assessed in blinded
      fashion. Fragmentation was defined as the presence of RSR' patterns and/or
      notching of the R/S wave in at least 2 contiguous leads. Analysis was limited to
      ECGs with QRS duration <120 ms. Overall prevalence of fragmentation was higher in
      cases (n=185; 64.9+/-13.8 years; 67.0% male) compared with controls (n=405;
      64.9+/-11.0 years; 64.7% male) (34.6% versus 26.9%, P=0.06). Lateral
      fragmentation was significantly more frequent in cases (8.1% versus 2.5%; P<0.
      01), with non-significant differences in anterior and inferior territories.
      Fragmentation in multiple territories (>=2) was also more likely to be observed
      in cases (9.7% versus 4.9%, P=0.02). In multivariable analysis with consideration
      of established SCD risk factors, lateral fragmentation was significantly
      associated with SCD (OR 2.84; 95% CI 1.01 to 8.02; P=0.05). CONCLUSION: QRS
      fragmentation, especially in the lateral territory is a potential risk marker for
      SCD independent of the ejection fraction, among obese/overweight subjects in the
      general population.

PMID- 25762805
TI  - Effect of prehospital induction of mild hypothermia on 3-month neurological
      status and 1-year survival among adults with cardiac arrest: long-term follow-up
      of a randomized, clinical trial.
AB  - BACKGROUND: Randomized trials of prehospital cooling after cardiac arrest have
      shown that neither prehospital cooling nor targeted temperature management
      differentially affected short-term survival or neurological function. In this
      follow-up study, we assess the association of prehospital hypothermia with
      neurological function at least 3 months after cardiac arrest and survival 1 year
      after cardiac arrest. METHODS AND RESULTS: There were 508 individuals who were
      discharged alive from hospitals in King County, Washington; 373 (73%) were
      interviewed by telephone 123+/-43 days after the initial event. Overall, 59% of
      the treatment group and 58% of the control group had Cerebral Performance
      Category (CPC) 1 or 2 (P=0.70), and 50% of the treatment group and 49% of the
      control group had slight disability or better by the Modified Rankin Scale (MRS;
      (P=0.35). One-year survival was 87% in the treatment group and 84% in the control
      group (P=0.42). Of those with CPC 1 at hospital discharge, 68% had CPC 1 or 2 at
      follow-up, and 59% had MRS of slight disability or better. Of 41 patients with
      CPC 3 or 4 at discharge, only 12% had CPC 2 at follow-up, and just 5% had MRS of
      slight disability or better. One-year survival was 92% for CPC 1 at discharge,
      but only 40% for CPC 4. CONCLUSION: In addition to excellent survival, patients
      who had good neurological function at discharge continued to have good function
      at least 3 months after the event. CLINICAL TRIAL REGISTRATION: URL:
      Clinicaltrials.gov. Unique identifier: NCT00391469.

PMID- 25762806
TI  - Top sources of dietary sodium from birth to age 24 mo, United States, 2003-2010.
AB  - BACKGROUND: Sodium intake is high in US children. Data are limited on the dietary
      sources of sodium, especially from birth to age 24 mo. OBJECTIVE: We identified
      top sources of dietary sodium in US children from birth to age 24 mo. DESIGN:
      Data from the NHANES 2003-2010 were used to examine food sources of sodium
      (population proportions and mean intakes) in 778 participants aged 0-5.9 mo, 914
      participants aged 6-11.9 mo, and 1219 participants aged 12-23.9 mo by
      sociodemographic characteristics. RESULTS: Overall, mean dietary sodium intake
      was low in 0-5.9-mo-old children, and the top contributors were formula (71.7%),
      human milk (22.9%), and commercial baby foods (2.2%). In infants aged 6-11.9 mo,
      the top 5 contributors were formula (26.7%), commercial baby foods (8.8%), soups
      (6.1%), pasta mixed dishes (4.0%), and human milk (3.9%). In children aged 12
      23.9 mo, the top contributors were milk (12.2%), soups (5.4%), cheese (5.2%),
      pasta mixed dishes (5.1%), and frankfurters and sausages (4.6%). Despite
      significant variation in top food categories across racial/ethnic groups,
      commercial baby foods were a top food contributor in children aged 6-11.9 mo, and
      frankfurters and sausages were a top food contributor in children aged 12-23.9
      mo. The top 5 food categories that contributed to sodium intake also differed by
      sex. Most of the sodium consumed (83-90%) came from store foods (e.g., from the
      supermarket). In children aged 12-23.9 mo, 9% of sodium consumed came from
      restaurant foods, and 4% of sodium came from childcare center foods. CONCLUSIONS:
      The vast majority of sodium consumed comes from foods other than infant formula
      or human milk after the age of 6 mo. Although the majority of sodium intake was
      from store foods, after age 12 mo, restaurant foods contribute significantly to
      intake. Reducing the sodium content in these settings would reduce sodium intake
      in the youngest consumers.

PMID- 25762807
TI  - Association of coffee intake with total and cause-specific mortality in a
      Japanese population: the Japan Public Health Center-based Prospective Study.
AB  - BACKGROUND: Despite the rising consumption of coffee worldwide, few prospective
      cohort studies assessed the association of coffee intake with mortality including
      total and major causes of death. OBJECTIVE: We aimed to investigate the
      association between habitual coffee drinking and mortality from all causes,
      cancer, heart disease, cerebrovascular disease, respiratory disease, injuries,
      and other causes of death in a large-scale, population-based cohort study in
      Japan. DESIGN: We studied 90,914 Japanese persons aged between 40 and 69 y
      without a history of cancer, cerebrovascular disease, or ischemic heart disease
      at the time of the baseline study. Subjects were followed up for an average of
      18.7 y, during which 12,874 total deaths were reported. The association between
      coffee intake and risk of total and cause-specific mortality was assessed by
      using a Cox proportional hazards regression model with adjustment for potential
      confounders. RESULTS: We showed an inverse association between coffee intake and
      total mortality in both men and women. HRs (95% CIs) for total death in subjects
      who consumed coffee compared with those who never drank coffee were 0.91 (0.86
      0.95) for <1 cup/d, 0.85 (0.81-0.90) for 1-2 cups/d, 0.76 (0.70-0.83) for 3-4
      cups/d, and 0.85 (0.75-0.98) for >5 cups/d (P-trend < 0.001). Coffee was
      inversely associated with mortality from heart disease, cerebrovascular disease,
      and respiratory disease. CONCLUSION: With this prospective study, we suggest that
      the habitual intake of coffee is associated with lower risk of total mortality
      and 3 leading causes of death in Japan.

PMID- 25762803
TI  - Circulating brain-derived neurotrophic factor concentrations and the risk of
      cardiovascular disease in the community.
AB  - BACKGROUND: Brain-derived neurotrophic factor (BDNF) is a pleiotropic peptide
      involved in maintaining endothelial integrity. It is unknown if circulating BDNF
      levels are associated with risk of cardiovascular disease (CVD). METHODS AND
      RESULTS: We prospectively investigated the association of circulating BDNF levels
      with cardiovascular events and mortality in 3687 participants (mean age 65 years,
      2068 women) from the Framingham Heart Study (FHS). Using a common nonsynonomous
      single nucleotide polymorphism (SNP) in the BDNF gene (rs6265), we then performed
      a Mendelian randomization experiment in the CARDIoGRAM (Coronary ARtery DIsease
      Genome-Wide Replication And Meta-Analysis) consortium (>22,000 coronary artery
      disease [CAD] cases, >60,000 controls) to investigate whether SNP rs6265 was
      associated with CAD in CARDIoGRAM and, if so, whether the effect estimate
      differed from that predicted based on FHS data. On follow-up (median 8.9 years),
      467 individuals (261 women) in FHS experienced a CVD event, and 835 (430 women)
      died. In multivariable-adjusted Cox regression, serum BDNF was associated
      inversely with CVD risk (hazard ratio [HR] per 1-SD increase 0.88, 95% CI 0.80 to
      0.97, P=0.01) and with mortality (HR 0.87, 95% CI 0.80 to 0.93, P=0.0002). SNP
      rs6265 was associated with BDNF concentrations (0.772 ng/mL increase per minor
      allele copy) in FHS. In CARDIoGRAM, SNP rs6265 was associated with CAD (odds
      ratio 0.957, 95% CI 0.923 to 0.992), a magnitude consistent with the predicted
      effect (HR per minor allele copy 0.99, 95% CI 0.98 to 1.0; P=0.06 for difference
      between predicted and observed effect). CONCLUSION: Higher serum BDNF is
      associated with a decreased risk of CVD and mortality. Mendelian randomization
      suggests a causal protective role of BDNF in the pathogenesis of CVD.

PMID- 25762809
TI  - Active video games and energy balance in male adolescents: a randomized crossover
      trial.
AB  - BACKGROUND: Active video games (AVGs) have been shown to acutely increase energy
      expenditure when compared with seated video games; however, the influence of AVGs
      on compensatory adjustments in energy intake and expenditure is largely unknown.
      OBJECTIVE: The aim was to examine the acute effects of AVGs on energy intake and
      expenditure. DESIGN: With the use of a randomized crossover design, 26 male
      adolescents (mean +/- SD age: 14.5 +/- 1.4 y) completed three 1-h experimental
      conditions: resting control, seated video game play (Xbox 360; Microsoft), and
      AVG play (Kinect Adventures on Xbox 360) followed by an ad libitum lunch. A
      validated food menu was used to assess food intake immediately after the
      conditions and for the remainder of the day, and a dietary record was used for
      the subsequent 3-d period. Energy expenditure was measured by using portable
      indirect calorimetry throughout each experimental condition, and an accelerometer
      was used to assess the subsequent 3-d period. Appetite sensations were assessed
      by using visual analog scales at different time points during the testing day.
      The primary outcomes were acute (immediately after the conditions and 24-h) and
      short-term (3-d) energy intake and expenditure. RESULTS: Energy expenditure was
      significantly higher (~145%; P < 0.001) during the AVG condition than during the
      resting control and seated video game conditions; however, no significant
      differences in energy expenditure were observed 24 h (~6%; P > 0.49) and 3 d
      after the experimental conditions (~3%; P > 0.82). No significant differences
      were observed in absolute energy intake immediately after the conditions (~2%; P
      > 0.94) or in absolute energy intake 24 h (~5%; P > 0.63) and 3 d (~9%; P > 0.53)
      after the experimental conditions. Finally, appetite sensations were similar
      between conditions at all time points (P > 0.05). CONCLUSIONS: The increase in
      energy expenditure promoted by a single session of Kinect AVG play is not
      associated with increased food intake but is compensated for after the
      intervention, resulting in no measurable change in energy balance after 24 h.
      These results suggest that the potential of Kinect to reduce the energy gap
      underlying weight gain is offset within 24 h in male adolescents. This trial was
      registered at clinicaltrials.gov as NCT01655901.

PMID- 25762808
TI  - Serum biomarkers of habitual coffee consumption may provide insight into the
      mechanism underlying the association between coffee consumption and colorectal
      cancer.
AB  - BACKGROUND: Coffee intake may be inversely associated with colorectal cancer;
      however, previous studies have been inconsistent. Serum coffee metabolites are
      integrated exposure measures that may clarify associations with cancer and
      elucidate underlying mechanisms. OBJECTIVES: Our aims were 2-fold as follows: 1)
      to identify serum metabolites associated with coffee intake and 2) to examine
      these metabolites in relation to colorectal cancer. DESIGN: In a nested case
      control study of 251 colorectal cancer cases and 247 matched control subjects
      from the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial, we
      conducted untargeted metabolomics analyses of baseline serum by using ultrahigh
      performance liquid-phase chromatography-tandem mass spectrometry and gas
      chromatography-mass spectrometry. Usual coffee intake was self-reported in a food
      frequency questionnaire. We used partial Pearson correlations and linear
      regression to identify serum metabolites associated with coffee intake and
      conditional logistic regression to evaluate associations between coffee
      metabolites and colorectal cancer. RESULTS: After Bonferroni correction for
      multiple comparisons (P = 0.05 / 657 metabolites), 29 serum metabolites were
      positively correlated with coffee intake (partial correlation coefficients: 0.18
      0.61; P < 7.61 * 10(-5)); serum metabolites most highly correlated with coffee
      intake (partial correlation coefficients >0.40) included trigonelline (N'
      methylnicotinate), quinate, and 7 unknown metabolites. Of 29 serum metabolites, 8
      metabolites were directly related to caffeine metabolism, and 3 of these
      metabolites, theophylline (OR for 90th compared with 10th percentiles: 0.44; 95%
      CI: 0.25, 0.79; P-linear trend = 0.006), caffeine (OR for 90th compared with 10th
      percentiles: 0.56; 95% CI: 0.35, 0.89; P-linear trend = 0.015), and paraxanthine
      (OR for 90th compared with 10th percentiles: 0.58; 95% CI: 0.36, 0.94; P-linear
      trend = 0.027), were inversely associated with colorectal cancer. CONCLUSIONS:
      Serum metabolites can distinguish coffee drinkers from nondrinkers; some caffeine
      related metabolites were inversely associated with colorectal cancer and should
      be studied further to clarify the role of coffee in the cause of colorectal
      cancer. The Prostate, Lung, Colorectal, and Ovarian trial was registered at
      clinicaltrials.gov as NCT00002540.

PMID- 25762812
TI  - Medication reconciliation: more than just a best possible medication history.

PMID- 25762810
TI  - Effects of resistance training with and without caloric restriction on physical
      function and mobility in overweight and obese older adults: a randomized
      controlled trial.
AB  - BACKGROUND: Resistance training (RT) improves muscle strength and overall
      physical function in older adults. RT may be particularly important in the obese
      elderly who have compromised muscle function. Whether caloric restriction (CR)
      acts synergistically with RT to enhance function is unknown. OBJECTIVE: As the
      primary goal of the Improving Muscle for Functional Independence Trial (I'M FIT),
      we determined the effects of adding CR for weight loss on muscle and physical
      function responses to RT in older overweight and obese adults. DESIGN: I'M FIT
      was a 5-mo trial in 126 older (65-79 y) overweight and obese men and women who
      were randomly assigned to a progressive, 3-d/wk, moderate-intensity RT
      intervention with a weight-loss intervention (RT+CR) or without a weight-loss
      intervention (RT). The primary outcome was maximal knee extensor strength;
      secondary outcomes were muscle power and quality, overall physical function, and
      total body and thigh compositions. RESULTS: Body mass decreased in the RT+CR
      group but not in the RT group. Fat mass, percentage of fat, and all thigh fat
      volumes decreased in both groups, but only the RT+CR group lost lean mass.
      Adjusted postintervention body- and thigh-composition measures were all lower
      with RT+CR except intermuscular adipose tissue (IMAT). Knee strength, power, and
      quality and the 4-m gait speed increased similarly in both groups. Adjusted
      postintervention means for a 400-m walk time and self-reported disability were
      better with RT+CR with no group differences in other functional measures,
      including knee strength. Participants with a lower percentage of fat and IMAT at
      baseline exhibited a greater improvement in the 400-m walk and knee strength and
      power. CONCLUSIONS: RT improved body composition (including reducing IMAT) and
      muscle strength and physical function in obese elderly, but those with higher
      initial adiposity experienced less improvement. The addition of CR during RT
      improves mobility and does not compromise other functional adaptations to RT.
      These findings support the incorporation of RT into obesity treatments for this
      population regardless of whether CR is part of the treatment. This trial was
      registered at clinicaltrials.gov as NCT01049698.

PMID- 25762811
TI  - LCZ696, Angiotensin II Receptor-Neprilysin Inhibitor, Ameliorates High-Salt
      Induced Hypertension and Cardiovascular Injury More Than Valsartan Alone.
AB  - BACKGROUND: LCZ696, an angiotensin receptor-neprilysin inhibitor, has recently
      been demonstrated to exert more beneficial effects on hypertensive or heart
      failure patients than conventional renin-angiotensin system blockers. However,
      the mechanism underlying the benefit of LCZ696 remains to be understood. The
      present study was undertaken to examine the effect of LCZ696 compared with
      valsartan on hypertension and cardiovascular injury. METHODS: (i) Using
      telemetry, we compared the hypotensive effect of LCZ696 and valsartan in
      spontaneously hypertensive rats (SHR) that were fed a high-salt diet followed by
      a low-salt diet. (ii) We also examined the comparative effect of LCZ696 and
      valsartan on salt loaded SHRcp, a model of metabolic syndrome. RESULTS: (i)
      LCZ696 exerted a greater blood pressure (BP) lowering effect than valsartan in
      SHR regardless of high-salt or low-salt intake. Additive BP reduction by LCZ696
      was associated with a significant increase in urinary sodium excretion and
      sympathetic activity suppression. (ii) LCZ696 significantly ameliorated cardiac
      hypertrophy and inflammation, coronary arterial remodeling, and vascular
      endothelial dysfunction in high-salt loaded SHRcp compared with valsartan.
      CONCLUSIONS: LCZ696 caused greater BP reduction than valsartan in SHR regardless
      of the degree of salt intake, which was associated with a significant enhancement
      in urinary sodium excretion and sympathetic activity suppression. Furthermore, an
      additive BP lowering effect of LCZ696 led to greater cardiovascular protection in
      hypertensive rats.

PMID- 25762813
TI  - [Not Available].

PMID- 25762814
TI  - Medication reconciliation in pediatric cardiology performed by a pharmacy
      technician: a prospective cohort comparison study.
AB  - BACKGROUND: Medication reconciliation reduces potential medication discrepancies
      and adverse drug events. The role of pharmacy technicians in obtaining best
      possible medication histories (BPMHs) and performing reconciliation at the
      admission and transfer interfaces of care for pediatric patients has not been
      described. OBJECTIVES: To compare the completeness and accuracy of BPMHs and
      reconciliation conducted by a pharmacy technician (pilot study) and by nurses
      and/or pharmacists (baseline). The severity of identified unintentional
      discrepancies was rated to determine their clinical importance. METHODS: This
      prospective cohort comparison study involved patients up to 18 years of age
      admitted to and/or transferred between the Cardiology ward and the Cardiac
      Critical Care Unit of a pediatric tertiary care teaching hospital. A pharmacy
      resident conducted two 3-week audits: the first to assess the completeness and
      accuracy of BPMHs and reconciliation performed by nurses and/or pharmacists and
      the second to assess the completeness and accuracy of BPMHs and reconciliation
      performed by a pharmacy technician. RESULTS: The total number of patients was 38
      in the baseline phase and 46 in the pilot period. There were no statistically
      significant differences between the baseline and pilot audits in terms of
      completion of BPMH (82% [28/34] versus 78% [21/27], p = 0.75) or completion of
      reconciliation (70% [23/33] versus 75% [15/20], p = 0.76) within 24 h of
      admission. Completeness of transfer reconciliation was significantly higher
      during the pilot study than at baseline (91% [31/34] versus 61% [11/18], p =
      0.022). No significant differences between the baseline and pilot audits were
      found in the proportions of patients with at least one BPMH discrepancy (38%
      [13/34] versus 22% [6/27], p = 0.27), at least one unintentional discrepancy upon
      admission (21% [7/33] versus 10% [2/20], p = 0.46), or at least one unintentional
      discrepancy at the transfer interface (6% [1/18] versus 3% [1/34], p = 0.58).
      None of the 16 unintentional discrepancies were rated as causing severe patient
      discomfort or clinical deterioration. CONCLUSIONS: A trained pharmacy technician
      can perform admission and transfer medication reconciliation for pediatric
      patients with completeness and accuracy comparable to those of nurses and
      pharmacists. Future studies should explore the sustainability and cost
      effectiveness of this practice model.

PMID- 25762815
TI  - Stability of Dabigatran Etexilate in Manufacturer's Blister Pack, Unit-Dose
      Packaging, and Community Pharmacy Blister Pack.
AB  - BACKGROUND: Dabigatran, a direct thrombin inhibitor, is indicated for the
      prevention and treatment of venous thromboembolism and for stroke prophylaxis in
      atrial fibrillation. The manufacturer recommends that dabigatran etexilate be
      retained in the original packaging until administration. Currently, no
      information exists about the stability of dabigatran etexilate outside its
      original packaging. OBJECTIVE: To evaluate the stability of dabigatran etexilate
      capsules over 120 days, with storage in the manufacturer's original packaging, in
      unit-dose packaging, and in community pharmacy blister packaging. METHODS:
      Commercially available dabigatran etexilate capsules (110 mg) were stored at room
      temperature (25 degrees C) in the manufacturer's original blister pack, in unit
      dose packaging, or in community pharmacy blister packs. Samples were collected
      from each container daily for the first 3 days, weekly up to 28 days, every other
      week until day 98, and at day 120. Suspensions were prepared, pH was evaluated,
      and samples were stored at -85 degrees C until analysis. Each sample was analyzed
      in duplicate by a validated, stability-indicating high-performance liquid
      chromatography - ultraviolet detection method. The capsules were considered
      stable if they maintained at least 90% of the initial concentration. RESULTS:
      Dabigatran etexilate capsules maintained 100.4% of the original concentration
      with 120 days of storage in the manufacturer's original blister pack, 98.7% with
      storage in unit-dose packaging, and 98.0% with storage in community pharmacy
      blister packs. There were no notable changes in appearance, ease of suspension of
      the capsule content, or pH over the 120-day period. CONCLUSION: Dabigatran
      etexilate 110-mg capsules were stable for 120 days with storage at room
      temperature in 3 types of packaging widely used in hospital and community
      settings.

PMID- 25762816
TI  - Professional use of social media by pharmacists.
AB  - BACKGROUND: A recent trend among health care professionals is the use of social
      media for professional purposes. These rapidly expanding media allow for timely
      and efficient access to health information, but they also carry the potential for
      increased liability. There is a paucity of research detailing how health care
      professionals, specifically pharmacists, use social media. OBJECTIVE: To
      characterize the use of social media by pharmacists in the Canadian province of
      Alberta and to identify independent determinants of and perceived barriers to
      using social media for professional purposes. METHODS: Data for this mixed
      methods study were collected by an online survey in March and April 2014. Alberta
      pharmacists were invited to participate via e-mail distributed by 2 professional
      organizations. RESULTS: The survey had 273 respondents. Of these, 226 (82.8%)
      stated that they had a social media account for either personal or professional
      purposes, and 138 (61.1%) of these reported using social media for professional
      purposes, although most respondents used social media predominantly for personal
      reasons. The most commonly reported social media applications were Facebook and
      Twitter, accessed primarily via smartphones. Of the 273 respondents, 206 (75.5%)
      had a Facebook account, and 101 (49.0%) of these used Facebook to some extent for
      professional purposes. Twitter users (104 [38.1%] of respondents) had a higher
      rate of professional utilization (57/104 [54.8%]). The most commonly identified
      barrier to using social media for professional purposes was concern over
      liability. Positive predictors of use of social media for professional purposes
      included younger age and fewer years of professional experience. Participants
      perceived the most beneficial aspect of social media (in professional terms) as
      connecting with pharmacist colleagues. CONCLUSION: More than 80% of pharmacists
      in Alberta reported that they had a social media account, and over half of them
      reported using their accounts for professional purposes. Although Facebook had a
      higher reported rate of utilization in general, a greater proportion of
      respondents reported using Twitter for professional purposes. Individuals and
      organizations seeking to expand their professional social media presence should
      focus on Twitter.

PMID- 25762817
TI  - An introduction to the fundamentals of randomized controlled trials in pharmacy
      research.

PMID- 25762819
TI  - Best of both worlds: a comparison of canadian and international best practices
      for hospital pharmacy services.

PMID- 25762818
TI  - Measuring anti-factor xa activity to monitor low-molecular-weight heparin in
      obesity: a critical review.
AB  - BACKGROUND: The choice of whether to monitor anti-factor Xa (anti-Xa) activity in
      patients who are obese and who are receiving low-molecular-weight heparin (LMWH)
      therapy is controversial. To the authors' knowledge, no systematic review of
      monitoring of anti-Xa activity in such patients has been published to date.
      OBJECTIVE: To systematically ascertain the utility of monitoring anti-Xa
      concentrations for LMWH therapy in obese patients. DATA SOURCES: MEDLINE (1946 to
      September 2014), the Cochrane Database of Systematic Reviews, Embase (1974 to
      September 2014), PubMed (1947 to September 2014), International Pharmaceutical
      Abstracts (1970 to September 2014), and Scopus were searched using the terms
      obesity, morbid obesity, thrombosis, venous thrombosis, embolism, venous
      thromboembolism, pulmonary embolism, low-molecular weight heparin, enoxaparin,
      dalteparin, tinzaparin, anti-factor Xa, anti-factor Xa monitoring, anti-factor Xa
      activity, and anti-factor Xa assay. The reference lists of retrieved articles
      were also reviewed. STUDY SELECTION AND DATA EXTRACTION: English-language studies
      describing obese patients treated with LMWH or reporting anti-Xa activity were
      reviewed using a 9-step decision-making algorithm to determine whether monitoring
      of LMWH therapy by means of anti-Xa activity in obesity is warranted. Studies
      published in abstract form were excluded. DATA SYNTHESIS: The analysis showed
      that anti-Xa concentrations are not strongly associated with thrombosis or
      hemorrhage. In clinical studies of LMWH for thromboprophylaxis in bariatric
      surgery, orthopedic surgery, general surgery, and medical patients, and for
      treatment of venous thrombo embolism and acute coronary syndrome, anti-Xa
      activity can be predicted from dose of LMWH and total body weight; no difference
      in clinical outcome was found between obese and non-obese participants.
      CONCLUSIONS: Routinely determining anti-Xa concentrations in obese patients to
      monitor the clinical effectiveness of LMWH is not warranted on the basis of the
      current evidence. Circumstances where measurement of anti-Xa concentration may
      help in clinical decision-making in either obese or non-obese patients would be
      cases where elimination of LMWH is impaired or there is an unexpected clinical
      response, as well as to confirm compliance with therapy or to identify deviation
      from predicted pharmacokinetics.

PMID- 25762820
TI  - Encephalopathy induced by combination therapy with valproic Acid and topiramate:
      challenging the utility of serum ammonia measurement.

PMID- 25762821
TI  - Iatrogenic thyrotoxicosis secondary to compounded liothyronine.

PMID- 25762822
TI  - Should influenza immunization be mandatory for all health care providers?

PMID- 25762823
TI  - CSHPmania.

PMID- 25762824
TI  - La SCPHmania.

PMID- 25762825
TI  - Une nouvelle annee : l'heure est au bilan.

PMID- 25762826
TI  - A new year-time for reconciliation.

PMID- 25762827
TI  - A multidimensional examination of the acculturation and psychological functioning
      of a sample of immigrant Chinese mothers in the US.
AB  - The present research used the cluster analysis method to examine the
      acculturation of immigrant Chinese mothers (ICMs), and the demographic
      characteristics and psychological functioning associated with each acculturation
      style. The sample was comprised of 83 first-generation ICMs of preschool children
      residing in Maryland, Unites States (US). Cluster analysis revealed four
      acculturation styles: psychologically-behaviorally integrated; psychologically
      behaviorally assimilated; psychologically-behaviorally undifferentiated; and
      psychologically-behaviorally separated. Assimilated mothers were the youngest at
      immigration and had resided in the US for the longest time. Separated mothers
      were older at immigration, resided in the US for a shorter time, were less
      educated, and had lower psychological functioning than mothers in the other
      clusters. However, there were no differences in demographic characteristics and
      psychological functioning between psychologically-behaviorally integrated and
      psychologically-behaviorally undifferentiated clusters. The importance of
      simultaneously assessing various cultural orientations and components of
      acculturation was highlighted.

PMID- 25762828
TI  - Recurrent respiratory papillomatosis by HPV: review of the literature and update
      on the use of cidofovir.
AB  - Recurrent respiratory papillomatosis is a viral induced disease characterised by
      exophytic epithelial lesions affecting the larynx. The problem with its treatment
      is the high recurrence of papilloma growth after surgical removal. The aim of our
      review is to analyse the actual use of cidofovir, an agent used in adjuvant
      therapy. We have reviewed 6 manuscripts that included a total of 118 patients.
      The parameters taken into account were: concentration of infiltrated cidofovir
      (mg/ml), therapeutic response, relapse-free time (months), side effects,
      genotypes (HPV-6/11/18) and evolution of dysplasia. Cidofovir was injected at
      concentrations from 2.5 to 15 mg/ml, therapeutic response was from 56.25% to
      82.3% and relapse-free time was from 10.05 to 49 months. There were 2 cases of
      dysplasia during therapy. Ten patients had been infected by HPV-6, 4 patients by
      HPV-11 and 10 patients by HPV-6 and HPV-11. The purposes of our review include
      the following: to stress that the juvenile form is more aggressive than other
      forms, to demonstrate than the drug has good adjuvant action although it does not
      significantly change the final response to the disease, to show that side effects
      are modest and, finally, to disprove the hypothesis that cidofovir may promote
      evolution towards dysplasia. In conclusion, combination of surgical removal and
      injection of cidofovir is associated with good response in recurrent respiratory
      papillomatosis. 

PMID- 25762829
TI  - Salvage surgery for locoregional recurrences of advanced pharyngolaryngeal
      squamous cell carcinoma after organ preservation failure.
AB  - Organ preservation treatment for advanced head and neck squamous cell carcinoma
      is associated with poor outcomes due to locoregional recurrences. Salvage surgery
      is the main therapeutic option for some of these patients. The aim of this study
      was to analyse the results of salvage surgery for advanced pharyngolaryngeal
      squamous cell carcinoma previously treated with radiochemotherapy. We performed a
      retrospective study on 38 patients (36 men, 2 women). The median age at diagnosis
      was 60 years with a mean follow-up period of 49.8 months. Recurrences were
      diagnosed at a mean of 395 days after finalising organ preservation treatment.
      Patients went under different salvage surgeries, including 22 total
      laryngectomies, 6 partial laryngectomies (3 transoral laser surgeries and 3
      opened surgeries), 8 functional neck dissections and 2 tongue base surgeries.
      Nineteen patients had no postoperative complications after a mean hospital stay
      of 2 weeks. However, 5 patients died of significant recurrent bleedings. There
      were 4 salivary fistulas that responded to conservative management, while 7
      patients had important pharyngostomas that required reconstruction with either
      regional or free flaps. The mean hospital stay was of 61.60 days for all
      patients. Five-year overall survival from diagnosis, overall survival after
      salvage surgery and survival after salvage surgery were 44.20, 37.90 and 45.70%,
      respectively. In summary, we conclude that salvage surgery is an optimal
      treatment for pharyngolaryngeal and regional recurrences and provides improvement
      in locoregional control and survival, despite the severe complications. 

PMID- 25762830
TI  - Pectoralis major myocutaneous flap for head and neck reconstruction: risk factors
      for fistula formation.
AB  - The pectoralis major myocutaneous flap (PMMF) is a safe and versatile flap used
      widely for head and neck cancer reconstructions, but one of the major and most
      feared complications is oro- or pharyngocutaneous fistula. Herein, we attempt to
      establish risk factors for fistula formation in reconstructions of mucosal
      defects in the head and neck using PMMF through retrospective analysis of PMMF
      performed during 3 years at a single institution, with a total of 84 procedures.
      There were 69 men and 15 women, with a mean age of 59.5 years. There were 15
      cases of partial flap loss, two total flap losses and 31 fistulas. The
      independent risk factors for fistula formation were preoperative serum hemoglobin
      < 13 g/dl, preoperative serum albumin < 3.4 g/dl and hypopharynx reconstruction.
      The PMMF is still a very useful flap and this is the first multivariate analysis
      analysing risk factors for fistula formation. These findings are helpful in
      selecting patients with elevated risk of fistula formation, and therefore
      preventive measures can be undertaken to avoid potentially serious complications.

PMID- 25762831
TI  - Versatility of the supraclavicular pedicle flap in head and neck reconstruction.
AB  - Head and neck surgery has witnessed an increase in microvascular reconstructive
      procedures with free flaps over the last 20 years as they offer efficient
      functional recovery. Nevertheless, under certain circumstances they may be
      contraindicated or cannot be used. We present the use of supraclavicular pedicled
      flap in three patients with different recipient sites. All patients had
      acceptable functional and aesthetic outcomes. Donor-site morbidity was
      satisfactory. Supraclavicular pedicled flap is not only an alternative to free
      flap reconstruction, but also a first-choice option in head and neck
      reconstructive surgery. 

PMID- 25762832
TI  - Calcitonin measurement in fine-needle aspirate washouts vs. cytologic examination
      for diagnosis of primary or metastatic medullary thyroid carcinoma.
AB  - Ultrasound-guided fine-needle aspiration biopsy cytology (FNAB-C) is able to
      detect approximately 63% of medullary thyroid carcinoma (MTC). The measurement of
      calcitonin in the needle washout (FNAB-CT) could improve its accuracy. Sixty-two
      FNAB-C were performed in 38 patients. Serum calcitonin (sCT) was measured before
      performing FNAB-C. After obtaining a FNAB-C specimen, the needle was washed with
      0.5 ml of saline solution to obtain the CT washouts. Receiver operating
      characteristic (RO C) analysis identified the cut-offs of FNAB-CT and FNAB
      CT/sCT. Eighteen MTC were found at final histology. RO C analysis indicated FNAB
      CT > 10.4 pg/ml and FNABCT/ sCT > 1.39 as more accurate cut-off values. Overall
      accuracy, positive (PPV) and negative predictive values (NPV) were 85%, 100 and
      83%, respectively, for FNAB-C, 97%, 100%, 96% for FNAB-CT and 90%, 83% and 93%
      for FNAB-CT/sCT. The integration of FNAB-C and FNAB-CT resulted in 98% overall
      accuracy, 100% PPV and 98% NPV; the integration of FNAB-C and FNAB-CT/sCT in 90%
      overall accuracy, 80% PPV and 95% NPV. One of 2 false negative FNAB-CT and one of
      3 false negative FNAB CT/sCT were correctly diagnosed by FNAB-C. Eight of 9 non
      diagnostic FNAB-C were correctly classified by FNAB-CT and 7 by FNAB CT/sCT. FNAB
      CT should integrate but not replace FNAB-C. FNAB-CT is particularly useful in the
      presence of non-diagnostic FNAB-C. 

PMID- 25762833
TI  - Aesthetic comparison between synthetic glue and subcuticular sutures in thyroid
      and parathyroid surgery: a single-blinded randomised clinical trial.
AB  - The aim of our study was to compare, in terms of aesthetic results, the use of
      synthetic glue to intradermal absorbable sutures in postthyroidectomy and
      parathyroidectomy wound closure in a single blinded, randomised, per protocol
      equivalence study. From September 2008 to May 2010, patients undergoing thyroid
      or parathyroid surgery (with an external approach) at the Otolaryngology
      Department of the University Hospital of Modena were assessed for eligibility. In
      total, 42 patients who had had synthetic glue application on surgical incisions
      (A) and 47 patients who had subcuticular sutures on their surgical incisions (B)
      were enrolled. The mean of the endpoint (based on the Wound Registry Scale) of
      group A at 10 days was 1.4, while that in group B (based on the Stony Brook Scar
      Evaluation Scale) was 2.9. Statistically significant (p = 0.002) and clinically
      significant (difference of the means = 1.5) differences in the aesthetic results
      were found between groups A and B at 10 days, with better results in group B. On
      the other hand, at 3 months, the mean of the endpoint in group A was 3.1 while
      that in group B was 2.8; no statistically significant (p = 0.62) or clinically
      significant (difference in means = 0.3) differences were found between groups A
      and B. In conclusion, synthetic glue differs from subcuticular suture in post
      thyroidectomy or post-parathyroidectomy incision for early aesthetic results,
      with better outcomes for subcuticular sutures. At 3 months, there were no
      differences in aesthetic outcomes between groups. Moreover, sex, incision length,
      age, cold/hot blade and correspondence of the incision with a wrinkle in the skin
      did not seem to influence aesthetic outcomes with this type of incision. 

PMID- 25762834
TI  - Voice disorders in primary school teachers.
AB  - Previous reports focusing on the high prevalence of voice disorders in teachers
      have suggested that vocal loading might be the main causal factor. The aim of our
      study was to assess the prevalence of voice disorders in a sample of primary
      school teachers and evaluate possible cofactors. Our sample was composed of 157
      teachers (155 females, mean age 46 years). Participants were asked to complete
      two selfadministrated questionnaires: one with clinical data, and the second an
      Italian validated translation of VHI (voice handicap index). On the same day they
      also underwent a laryngostroboscopic exam and logopedic evaluation. The results
      were compared with those of a control group composed of accompanying individuals.
      Teachers presented a higher rate of abnormalities at laryngostroboscopic
      examination than the control group (51.6% vs. 16%, respectively). Among these,
      7.1% presented nodules. In our sample, vocal fold disorders were not correlated
      with years of teaching, smoking, coffee consumption, or levels of anxiety. Our
      findings are in agreement with previous reports on the prevalence of pathologic
      disorders among teachers; nonetheless, the prevalence of nodules was lower than
      in previous investigations, and voice loading was not correlated with
      laryngostroboscopic findings. Current Italian law does not include any guidance
      regarding voice education and screening in subjects with high vocal loading. Our
      work stresses the need for such legislation. 

PMID- 25762835
TI  - STANDING, a four-step bedside algorithm for differential diagnosis of acute
      vertigo in the Emergency Department.
AB  - Vertigo is generally due to a benign disorder, but it is the most common symptom
      associated with misdiagnosis of stroke. In this pilot study, we preliminarily
      assessed the diagnostic performance of a structured bedside algorithm to
      differentiate central from non-central acute vertigo (AV). Adult patients
      presenting to a single Emergency Department with vertigo were evaluated with
      STANDING (SponTAneous Nystagmus, Direction, head Impulse test, standiNG) by one
      of five trained emergency physicians or evaluated ordinarily by the rest of the
      medical staff (control group). The gold standard was a complete audiologic
      evaluation by a clinicians who are experts in assessing dizzy patients and
      neuroimaging. Reliability, sensibility and specificity of STANDING were
      calculated. Moreover, to evaluate the potential clinical impact of STANDING,
      neuroimaging and hospitalisation rates were compared with control group. A total
      of 292 patients were included, and 48 (16.4%) had a diagnosis of central AV.
      Ninety-eight (33.4%) patients were evaluated with STANDING. The test had good
      interobserver agreement (k = 0.76), with very high sensitivity (100%, 95%CI 72.3
      100%) and specificity (94.3%, 95%CI 90.7-94.3%). Furthermore, hospitalisation and
      neuroimaging test rates were lower in the STANDING than in the control group
      (27.6% vs. 50.5% and 31.6% vs. 71.1%, respectively). In conclusion, STANDING
      seems to be a promising simple structured bedside algorithm that in this
      preliminary study identified central AV with a very high sensitivity, and was
      associated with significant reduction of neuroimaging and hospitalisation rates. 

PMID- 25762836
TI  - Combined endoscopic-microscopic approach for vestibular schwannoma removal:
      outcomes in a cohort of 81 patients.
AB  - Patients affected by vestibular schwannomas typically report a number of symptoms
      and minor disabilities after surgery. Therefore, surgeons dealing with this
      pathology should also try to achieve a good QoL for patients who have undergone
      tumour removal. The aim of this study was to analyse QoL in subjects undergoing
      surgery for vestibular schwannomas and to try to establish a relationship with
      both the tumour size and post-surgical alterations (e.g. facial motor
      dysfunctions, difficulties in balance, persistence of headache and tinnitus). A
      retrospective analysis was performed on a consecutive series of 81 patients
      affected by vestibular schwannomas and treated by a combined microscopic
      endoscopic approach. Three groups of patients were identified on the basis of
      tumour size. Group 1 (lesions < 25 mm) with 31 patients (38%); Group 2 (lesions >
      26 mm and < 40 mm) with 39 patients (48%); Group 3 (lesions > 41 mm) with 11
      patients (14%). Data obtained with the Short Form Questionnaire showed a
      statistically significant difference in QoL in those undergoing intervention
      compared with a control group of healthy subjects. The Glasgow Benefit Inventory
      Questionnaire showed that 25 (31%) patients felt better, 11 (14%) felt similarly,
      and 45 (55%) felt poorer health conditions in comparison to the pre-surgical
      period. Concerning the relationship between preservation of facial nerve function
      and QoL, using the Glasgow Health Status Inventory, it appeared that only 34% of
      subjects with good facial nerve function (RGS grade I-II) complained of worsening
      of QoL, while 45% of those with serious facial nerve injury (RGS grade IV-V)
      referred poorer QoL. Moreover, the possibility of recovery of facial nerve
      function during the months following surgery was clearly highlighted by our
      analysis. Our study confirmed the close relation between tumour size and post
      surgical QoL, which is worse for patients affected by larger lesions. 

PMID- 25762837
TI  - Barbed anterior pharyngoplasty: an evolution of anterior palatoplasty.
AB  - We present a new surgical technique for the treatment of snoring and mild
      obstructive sleep apnoea syndrome. This is a modification of anterior
      palatoplasty, and its main features are the use of self-locking (barbed) threads
      and the possibility of stabilise the palatal suture by fixing it to anatomical
      bone and fibrous structures. The technique is described in detail and some
      preliminary results are presented. 

PMID- 25762839
TI  - Making mistakes in interventional radiology.

PMID- 25762838
TI  - Late treatment of orbital fractures: a new analysis for surgical planning.
AB  - Surgical treatment of orbital fractures should be performed without delay; in
      some cases acute management is not possible due to general conditions and might
      be delayed for weeks or months. In the latter case, the fractured fragments can
      consolidate improperly, causing secondary deformities of the orbital region with
      aesthetic and functional alteration. Surgical planning of secondary deformities
      is critical for adequate pre-operative planning. In the last decade an increasing
      number of dedicated software applications for surgical planning have been
      developed. Standard computed tomography (CT) or the relatively new cone beam CT
      can be used for diagnostic purposes, pre-surgical visual treatment outcome and
      virtual surgery. In this report, the authors propose their pre-operative planning
      analysis for surgical correction of secondary deformities of orbital fractures.
      The treatment of orbital fracture must, in fact, analyse not only the bone
      structures but the soft tissue and surrounding periorbital region. The position
      of the orbit in the space should be determined in relation to the surrounding
      structures compared to the contralateral side, if this is not affected by the
      trauma or pre-existing malformations. 

PMID- 25762840
TI  - Tumor lysis syndrome and primary hepatic malignancy: case presentation and review
      of the literature.
AB  - Tumor lysis syndrome (TLS) represents a constellation of laboratory and clinical
      derangements that can occur following treatment of malignancies with high
      cellular turnover. Most commonly noted in hematologic malignancies, TLS has been
      reported to occur following liver-directed therapy in the form of both ablative
      therapies and transarterial therapies. Classification schemes exist, as do
      established diagnostic criteria, to aid in the definitive diagnosis of TLS. In
      addition, treatment algorithms are reported for patients with the diagnosis of
      TLS. This manuscript will review the risk factors associated with the development
      of TLS, the diagnostic criteria used, and treatment and preventative strategies
      employed. In addition, an algorithm for the diagnosis and treatment of TLS will
      be provided. 

PMID- 25762841
TI  - Cerebral Embolization of Ethiodized Oil following Intranodal Lymphangiography.
AB  - Intranodal lymphangiography (IL) has supplanted pedal lymphangiography (PL) as an
      easier and more practical approach to opacifying lymphatic vessels for
      interventional radiologists treating refractory chyle leaks. As more
      interventional radiologists-many of who are not trained in or have not performed
      PL-incorporate IL into their practice, it is imperative that they be familiar
      with the risks of lymphangiography, including pulmonary and systemic embolization
      of oily contrast material. Herein, the authors report a devastating case of
      cerebral embolization of ethiodized oil following IL and review the literature
      regarding systemic embolization following lymphangiography. 

PMID- 25762842
TI  - Massive Hemorrhage from Arterial Access during Intracranial Aneurysm Stent
      Assisted Embolization: Endovascular Diagnosis and Therapy.
AB  - Massive hemorrhage from arterial access in patients receiving anticoagulation and
      antiplatelet therapy is a rare but potentially devastating complication. The
      authors present a patient who developed a large retroperitoneal and anterior
      abdominal wall hemorrhage following an unintentional and unrecognized arterial
      injury during an endovascular procedure. Reversal of anticoagulation in patients
      who have undergone stent-assisted coil embolization of intracranial aneurysms is
      an undesirable approach due to the risk of thromboembolism; rather, transcatheter
      embolization of the bleeding source should be considered. 

PMID- 25762843
TI  - Acute pancreatitis after transarterial chemoembolization of hepatocellular
      carcinoma with drug-eluting beads.
AB  - Nontarget embolization is a relatively common cause of post-chemoembolization
      complications. Clinical presentation following nontarget embolization varies from
      minimal to fatal, and oftentimes relates to the vascular distribution embolized
      rather than the amount or type of embolic agent. Post-chemoembolization
      pancreatitis is an uncommon complication, but one that is known to occur. The
      following manuscript presents a case of post-chemoembolization pancreatitis, and
      suggests methods to decrease this complication as well as treatment once the
      complication occurs. 

PMID- 25762844
TI  - Skin Necrosis Resulting from Nontarget Embolization of the Falciform Artery
      during Transarterial Chemoembolization with Drug-Eluting Beads.
AB  - Intra-arterial embolic therapies are a mainstay of liver-directed therapies to
      palliate symptoms, improve survival, and bridge patients to transplantation.
      Vascular anatomy and type of embolic used can lead to complications of nontarget
      embolization with varying clinical consequences. This case report describes a
      rare, nontarget embolization of the falciform artery leading to supraumbilical
      skin necrosis. 

PMID- 25762845
TI  - Major bleeding after percutaneous image-guided biopsies: frequency, predictors,
      and periprocedural management.
AB  - Major bleeding remains an uncommon yet potentially devastating complication
      following percutaneous image-guided biopsy. This article reviews two cases of
      major bleeding after percutaneous biopsy and discusses the frequency, predictors,
      and periprocedural management of major postprocedural bleeding. 

PMID- 25762846
TI  - Procedural and indwelling complications with inferior vena cava filters:
      frequency, etiology, and management.
AB  - Inferior vena cava (IVC) filters are commonly used in select high-risk patients
      for the prevention of pulmonary embolism. Potentially serious complications can
      arise from the use of IVC filters, including thrombosis of the filter itself and
      filter fragment embolization. This article discusses the utility of IVC filters
      and reviews the management of two cases of filter-related complications. 

PMID- 25762847
TI  - Complications of transjugular biopsies.
AB  - Transvenous biopsy was first performed in 1964 by Charles Dotter. Now routinely
      performed in the liver and kidney by interventional radiologists, the
      transjugular approach to biopsy has assumed a central role in coagulopathic
      patients. Major arterial complications from transjugular liver and renal biopsy
      are rare. In this article, the authors describe such complications in both organs
      that necessitated selective endovascular coil embolization. 

PMID- 25762848
TI  - Hepatocellular carcinoma rupture following transarterial chemoembolization.
AB  - As the incidence of primary and metastatic liver cancer increases, minimally
      invasive treatment methods such as transarterial chemoembolization (TACE) have
      gained momentum as their efficacy and safety profile have been validated.
      Complications of TACE are rare and typically well tolerated. A unique
      complication is tumor rupture with hemorrhage. Reports of hepatocellular
      carcinoma (HCC) rupture after TACE are limited. It is critical to recognize this
      complication and understand the treatment options, which range from conservative
      to surgical management. This report describes a case of HCC rupture following
      TACE successfully managed with coil embolization. 

PMID- 25762849
TI  - Percutaneous management of chronic central venous occlusive disease.

PMID- 25762850
TI  - Medical malpractice issues related to interventional radiology complications.

PMID- 25762851
TI  - Copper-Catalyzed Synthesis of N-Aryl and N-Sulfonyl Indoles from 2-Vinylanilines
      with O2 as Terminal Oxidant and TEMPO as Co-Catalyst.
AB  - A copper-catalyzed intramolecular alkene oxidative amination that utilizes TEMPO
      as co-catalyst and O2 as the terminal oxidant has been developed. The method
      furnishes N-aryl and N-sulfonyl indoles from N-aryl and N-sulfonyl 2
      vinylanilines, respectively. Additionally, sequential copper-catalyzed reactions
      where initial Chan-Lam coupling of 2-vinylanilines with arylboronic acids is
      followed by oxidative amination of the alkene can generate N-aryl indoles in one
      pot.

PMID- 25762852
TI  - Reduced serum butyrylcholinesterase activity indicates severe systemic
      inflammation in critically ill patients.
AB  - Systemic inflammation is an immune response to a nonspecific insult of either
      infectious or noninfectious origin and remains a challenge in the intensive care
      units with high mortality rate. Cholinergic neurotransmission plays an important
      role in the regulation of the immune response during inflammation. We
      hypothesized that the activity of butyrylcholinesterase (BChE) might serve as a
      marker to identify and prognose systemic inflammation. By using a point-of-care
      testing (POCT) approach we measured BChE activity in patients with severe
      systemic inflammation and healthy volunteers. We observed a decreased BChE
      activity in patients with systemic inflammation, as compared to that of healthy
      individuals. Furthermore, BChE activity showed an inverse correlation with the
      severity of the disease. Although hepatic function has previously been found
      essential for BChE production, we show here that the reduced BChE activity
      associated with systemic inflammation occurs independently of and is thus not
      caused by any deficit in liver function in these patients. A POCT approach, used
      to assess butyrylcholinesterase activity, might further improve the therapy of
      the critically ill patients by minimizing time delays between the clinical
      assessment and treatment of the inflammatory process. Hence, assessing
      butyrylcholinesterase activity might help in early detection of inflammation. 

PMID- 25762854
TI  - Laparoscopic treatment of 1522 adnexal masses: an 8-year experience.
AB  - Objective. To reevaluate the long-term effectiveness and safety of laparoscopy in
      benign ovarian pathology. Materials and Methods. 1522 women with benign adnexal
      cysts, laparoscopically treated in the 3rd Department of Ob/Gyn, General
      University hospital "Attikon" and "Lito" Maternity Hospital between July 1998 and
      December 2006, were included. Results. The diagnosis in 1222 (80,6%) cases was
      endometriosis of the ovary, 60 (4%) hydrosalpinx, 51 (3,3%) serous cystadenomas,
      44 (2,9%) dermoid ovarian cyst, 38 (2,5%) borderline tumors, 35 (2,3%) unruptured
      follicles, and 33 (2,2%) paraovarian cysts. In 174 cases (11,5%) laparoscopy was
      converted to laparotomy due to technical difficulties or suspicion of cancer. In
      particular, laparotomy was performed in 119 (8%) women due to severe adhesions
      and 18 (1,2%) women due to bleeding that could not be controlled safely by
      laparoscopy. In 36 (2,4%) women frozen section during operation revealed
      malignancy and laparoscopy was converted to laparotomy. A few operative
      complications were recorded like post-op fever, small hematomas at the trocar
      entries. Conclusions. Laparoscopic surgery seems to offer significant advantages
      such as reduced hospital stay, less adverse effects, better quality of life, and
      superior vision especially on surgical treatment of cases like endometriosis. 

PMID- 25762853
TI  - Mechanisms Underlying Sexual Violence Exposure and Psychosocial Sequelae: A
      Theoretical and Empirical Review.
AB  - Sexual violence is associated with a range of negative mental health and
      behavioral sequelae, including posttraumatic stress disorder (PTSD), depression,
      substance abuse/dependence, risky sexual behavior, and interpersonal relationship
      problems. However, mechanisms underlying these associations are not well
      understood. Identifying mechanisms that explain linkages between sexual violence
      and poor outcomes is of paramount importance in determining when and how to
      intervene to prevent or reduce the magnitude of these outcomes. This review
      focuses on theories that have been proposed to explain risk of negative outcomes
      among sexual violence victims, including the development of traumagenic dynamics
      and emotion dysregulation. We also review promising biological mechanisms that
      may explain the risk of negative outcomes among sexual violence victims,
      including studies concerned with epigenetic and neurobiological mechanisms.

PMID- 25762855
TI  - It's All of the Above: Benefits of Working for Individuals with Spinal Cord
      Injury.
AB  - BACKGROUND: The majority of research on employment among persons with spinal cord
      injury (SCI) focuses on the employment rate at a given point in time to the
      exclusion of quality employment outcomes. OBJECTIVE: To identify the employment
      outcomes of greatest importance as defined by those with SCI who have worked
      since injury. METHODS: A qualitative approach was used with 6 focus groups at 2
      sites (Minnesota and Georgia). Participants (N = 44) were a minimum of 10 years
      after injury and had been employed at some point after SCI. We identified
      participants through a 40-year longitudinal study of SCI and a community
      resource. A combination of homogeneous (race/ethnic minority group, female group)
      and heterogeneous groups were convened. A semi-structured interview format
      queried participants about personal, environmental, and policy-related factors
      that impacted obtaining, maintaining, and advancing in employment. RESULTS: Seven
      overlapping themes were identified under the 2 broad categories of compensation
      and subjective well-being: (1) salary and what it can support, (2) health
      insurance and other fringe benefits, (3) promotions and recognition, (4) social
      connection and support, (5) job satisfaction and enjoyment from working, (6)
      making a difference and helping others, and (7) psychological and emotional
      health. CONCLUSION: The results indicate several common themes among persons with
      SCI who have successful employment histories, suggesting that the benefits of
      employment are multifaceted and go beyond monetary compensation.

PMID- 25762856
TI  - Occupational characteristics of adults with pediatric-onset spinal cord injury.
AB  - BACKGROUND: Employment rates among individuals with spinal cord injury (SCI) are
      lower than in the general population and little is known about the specific
      occupations in which they are employed. OBJECTIVES: To describe specific
      occupations of adults with pediatric-onset SCI using the 2010 Standard
      Occupational Classification (SOC) system and to determine associations between
      SOC occupations and demographic factors. METHODS: Cross-sectional data specific
      to education and employment were collected from the last interviews of a larger
      longitudinal study. Occupations were categorized according to the 2010 SOC
      system. SOC groups were compared within gender level of injury and final
      education. RESULTS: Of the 461 total participants 219 (47.5%) were employed and
      specific occupations were available for 179. Among the SOC groups Education Law
      Community Service Arts and Media Occupations were most prevalent (30.2%) followed
      by Management Business and Finance Occupations (21.1%) Computer Engineering and
      Science Occupations (10.6%) Administrative and Office Support Occupations (10.0%)
      Service Occupations (7.3%) Healthcare Practitioners and Technical Occupations
      (3.9%) and Production Occupations (3.4%). Differences were found in the
      distribution of SOC groups between gender levels of injury and final education
      groups. CONCLUSION: A wide variety of occupations were reported in adults with
      pediatric-onset SCI generally in concordance with final education and functional
      ability levels.

PMID- 25762857
TI  - Facilitators and barriers to employment among veterans with spinal cord injury
      receiving 12 months of evidence-based supported employment services.
AB  - BACKGROUND: Return to work is associated with positive rehabilitation outcomes
      for persons with spinal cord injury (SCI); however, more research is needed on
      vocational support for persons with disabilities seeking employment. OBJECTIVE:
      The association between facilitators and barriers of employment and employment
      outcome was examined among Veterans with SCI who participated in an evidence
      based supported employment (EBSE) program. METHODS: Using a mixed-methods, nested
      case-control design, data on facilitators and barriers to employment were
      extracted from qualitative interviews and quantitative measures administered in
      person to 34 Veterans with SCI who completed 12 months of an EBSE program.
      Participants who did (case) and did not (control) obtain competitive employment
      were matched on time since SCI. Facilitators and barriers to employment were
      compared between the groups. RESULTS: Self-report measures administered at
      baseline were examined; there were no statistically significant factors that
      predicted employment outcomes after 12 months of EBSE program participation.
      Qualitative interview data revealed program-specific facilitators and Veteran
      characteristics that were associated with employment outcomes. CONCLUSIONS:
      Qualitative data illustrate how the integration of the vocational rehabilitation
      specialist on the medical team is helpful for addressing identified disability
      specific barriers, including practical matters such as transportation and
      caregiving schedules, to facilitate employment outcomes.

PMID- 25762858
TI  - Vocational rehabilitation in spinal cord injury: what vocational service
      activities are associated with employment program outcome?
AB  - BACKGROUND: Designing effective vocational programs for persons with spinal cord
      injury (SCI) is essential for improving return to work outcome following injury.
      The relationship between specific vocational services and positive employment
      outcome has not been empirically studied. OBJECTIVE: To examine the association
      of specific vocational service activities as predictors of employment. METHOD:
      Secondary analysis of a randomized, controlled trial of evidence-based supported
      employment (EBSE) with 12-month follow-up data among 81 Veteran participants with
      SCI. RESULTS: Primary activities recorded were vocational counseling (23.9%) and
      vocational case management (23.8%). As expected, job development and employment
      supports were the most time-consuming activities per appointment. Though the
      amount of time spent in weekly appointments did not differ by employment outcome,
      participants obtaining competitive employment averaged significantly more
      individual activities per appointment. Further, for these participants, job
      development or placement and employment follow-along or supports were more likely
      to occur and vocational counseling was less likely to occur. Community-based
      employment services, including job development or placement and employment follow
      along or supports as part of a supported employment model, were associated with
      competitive employment outcomes. Office-based vocational counseling services,
      which are common to general models of vocational rehabilitation, were associated
      with a lack of employment. CONCLUSIONS: Vocational services that actively engage
      Veterans with SCI in job seeking and acquisition and that provide on-the-job
      support are more likely to lead to employment than general vocational counseling
      that involves only job preparation.

PMID- 25762859
TI  - Heart rate response during underwater treadmill training in adults with
      incomplete spinal cord injury.
AB  - BACKGROUND: Walking on a submerged treadmill can improve mobility in persons
      displaying lower limb muscle weakness and balance deficits. Little is known,
      however, regarding the effect of water treadmill exercise on cardiac performance
      in persons with incomplete spinal cord injury (iSCI). OBJECTIVE: To assess heart
      rate response during underwater treadmill training (UTT) in adults with iSCI.
      METHODS: Seven males and 4 females with iSCI (age = 48 +/- 13 years; 5 +/- 8
      years after injury) completed 8 weeks of UTT (3 sessions per week; 3 walks per
      session) incorporating individually determined walking speeds, personalized
      levels of body weight unloading, and gradual, alternating increases in speed and
      duration. Heart rate was monitored during the last 15 seconds of the final 2
      minutes of each walk. RESULTS: Over the course of 3 biweekly periods in which
      walking speed remained constant, heart rate fell by 7% (7 +/- 1 b*min(-1); P <
      .001) in weeks 2 and 3, 14% (17 +/- 6 b*min(-1); P < .001) in weeks 4 and 5, and
      17% (21 +/- 11 b*min(-1); P < .001) in weeks 6 and 7. CONCLUSION: In adults with
      iSCI, progressively greater absolute and relative reductions in submaximal
      exercise heart rate occurred after 2 months of UTT featuring a systematic
      increase in training volume.

PMID- 25762860
TI  - A narrative literature review to direct spinal cord injury patient education
      programming.
AB  - PURPOSE: To summarize the evidence on SCI-related education literature, while
      looking at potential barriers, solutions, benefits, and patient preferences
      regarding SCI patient education. METHOD: A literature review was conducted using
      5 electronic databases. Quality appraisal instruments were designed to determine
      the methodological rigor of the quantitative and qualitative studies found.
      Selected articles were read in their entirety and themes were abstracted.
      RESULTS: Fourteen articles met the inclusion criteria for this narrative
      literature review, all of which were based on research studies. Seven of these 14
      were quantitative studies, 3 were qualitative studies, and 4 were mixed-methods
      studies. CONCLUSION: To improve SCI education during rehabilitation, programs
      should maximize the receptiveness of newly injured patients to SCI-related
      information, optimize the delivery of SCI education, increase the number of
      opportunities for learning, promote and support lifelong learning, and include
      patient and program evaluation. How these strategies are specifically implemented
      needs to be determined by program management in consultation with various
      stakeholders, whilst considering the unique characteristics of the rehabilitation
      facility.

PMID- 25762862
TI  - Development, construction, and content validation of a questionnaire to test
      mobile shower commode usability.
AB  - BACKGROUND: Usability is an emerging domain of outcomes measurement in assistive
      technology provision. Currently, no questionnaires exist to test the usability of
      mobile shower commodes (MSCs) used by adults with spinal cord injury (SCI).
      OBJECTIVE: To describe the development, construction, and initial content
      validation of an electronic questionnaire to test mobile shower commode usability
      for this population. METHODS: The questionnaire was constructed using a mixed
      methods approach in 5 phases: determining user preferences for the
      questionnaire's format, developing an item bank of usability indicators from the
      literature and judgement of experts, constructing a preliminary questionnaire,
      assessing content validity with a panel of experts, and constructing the final
      questionnaire. RESULTS: The electronic Mobile Shower Commode Assessment Tool
      Version 1.0 (eMAST 1.0) questionnaire tests MSC features and performance during
      activities identified using a mixed-methods approach and in consultation with
      users. It confirms that usability is complex and multidimensional. The final
      questionnaire contains 25 questions in 3 sections. The eMAST 1.0 demonstrates
      excellent content validity as determined by a small sample of expert clinicians.
      CONCLUSION: The eMAST 1.0 tests usability of MSCs from the perspective of adults
      with SCI and may be used to solicit feedback during MSC design, assessment,
      prescription, and ongoing use. Further studies assessing the eMAST's psychometric
      properties, including studies with users of MSCs, are needed.

PMID- 25762861
TI  - Safety and efficacy of medically performed tongue piercing in people with
      tetraplegia for use with tongue-operated assistive technology.
AB  - BACKGROUND: Individuals with high-level spinal cord injuries need effective ways
      to perform activities. OBJECTIVES: To develop and test a medically supervised
      tongue-piercing protocol and the wearing of a magnet-containing tongue barbell
      for use with the Tongue Drive System (TDS) in persons with tetraplegia. METHODS:
      Volunteers with tetraplegia underwent initial screening sessions using a magnet
      glued on the tongue to activate and use the TDS. This was followed by tongue
      piercing, insertion of a standard barbell, a 4-week healing period, and an
      exchange of the standard barbell for a magnet-containing barbell. This was then
      used twice weekly for 6 to 8 weeks to perform computer tasks, drive a powered
      wheelchair, accomplish in-chair weight shifts, and dial a phone. Symptoms of
      intraoral dysfunction, change in tongue size following piercing, and subjective
      assessment of receiving and wearing a magnet-containing tongue barbell and its
      usability with the TDS were evaluated. RESULTS: Twenty-one volunteers underwent
      initial trial sessions. Thirteen had their tongues pierced. One individual's
      barbell dislodged during healing resulting in tongue-tract closure. Twelve had
      the barbell exchanged for a magnet-containing barbell. One subject withdrew for
      unrelated issues. Eleven completed the TDS testing sessions and were able to
      complete the assigned tasks. No serious adverse events occurred related to
      wearing or using a tongue barbell to operate the TDS. CONCLUSIONS: Using careful
      selection criteria and a medically supervised piercing protocol, no excess risk
      was associated with tongue piercing and wearing a tongue barbell in people with
      tetraplegia. Participants were able to operate the TDS.

PMID- 25762863
TI  - Neuromuscular electrical stimulation training increases intermuscular fascial
      length but not tendon cross-sectional area after spinal cord injury.
AB  - OBJECTIVE: To determine the effects of 12 weeks of neuromuscular electrical
      stimulation (NMES) training with ankle weights on intermuscular fascial length
      and patellar tendon cross-sectional area (CSA) in persons with spinal cord injury
      (SCI). METHODS: This study was a pre-post intervention. Seven men with motor
      complete SCI were randomly assigned to a resistance training plus diet (RT +
      diet) group (n = 4) or a diet control group (n = 3). Participants in the RT +
      diet group were enrolled in a 12-week leg extension weight-lifting program via
      surface NMES of the knee extensor muscle group. The length of mid-thigh
      intermuscular fascia and the patellar tendon CSA were measured using MRI.
      RESULTS: In the RT + diet group, a nonsignificant 8% increase in the CSA of the
      patellar tendon (P = .14) was noted. The length of the mid-thigh intermuscular
      fascia increased by 19% and 23% in the right (P = .029) and left (P = .015) legs,
      respectively, with no changes in the diet control group. Positive relationships
      were noted between skeletal muscle CSAs of the whole thigh (r = 0.77, P = .041)
      and knee extensors (r = 0.76, P = .048) and intermuscular fascial length.
      CONCLUSION: The preliminary results suggest that noncontractile connective tissue
      structures of the knee extensors respond differently to NMES training after SCI.
      Skeletal muscle hypertrophy is associated with an increase in the intermuscular
      fascial length.

PMID- 25762864
TI  - Dexmedetomidine augments the effect of lidocaine: power spectrum and nerve
      conduction velocity distribution study.
AB  - BACKGROUND: In this study, the individual and combined inhibitory effects of
      dexmedetomidine and lidocaine on the conduction group of isolated nerve were
      investigated by determining conduction velocity distribution (CVD) and power
      spectrum. METHODS: Electrophysiological compound action potential (CAP)
      recordings were conducted on isolated rat sciatic nerve before (Con) and 20
      minutes after exposure to 1 mM lidocaine (Lido), 21pM dexmedetomidine (Dex) and
      their combination (Lido + Dex). Then for CVD, mathematical model and for power
      spectrum Fast Fourier analysis were conducted. RESULTS: Dexmedetomidine alone
      made no significant difference in shape and duration of CAPs as compared to Con,
      on the other hand lidocaine depresses amplitude and prolongs the duration of
      CAPs, but not more than combination of dexmedetomidine and lidocaine can do.
      Lidocaine caused a shift in the CVD histogram to relatively slower conducting
      group significantly while dexmedetomidine did not cause any significant change as
      compared to Control. Lidocaine, when combined with dexmedetomidine revealed a
      remarkable effect on the whole CVD histogram by causing almost complete blockage
      of fast conducting nerve fibers. The relative number of fibers in CVD is
      conserved for separate applications of anesthetics, but not for their
      combination. As in CVD, power spectrum shifted from higher to lower frequency
      region by lidocaine and significantly for lidocaine combined with dexmedetomidine
      application. Shifts for dexmedetomidine applied group were seen beggarly.
      CONCLUSIONS: We have concluded that dexmedetomidine alone did not influence nerve
      conduction, but when it is used with lidocaine it augments neural conduction
      blockage effect, especially on fast conducting nerve fibers.

PMID- 25762865
TI  - MicroRNA-181b regulates endotoxin tolerance by targeting IL-6 in macrophage
      RAW264.7 cells.
AB  - Interleukin 6 (IL-6) is a major pro-inflammatory cytokine and dysregulation of IL
      6 is relevant to many inflammatory diseases. Endotoxin induced tolerance of IL-6
      is an important mechanism to avoid the excessive immune reaction. But to date,
      the molecular mechanisms of endotoxin tolerance of IL-6 remain unclear. Here we
      reported that IL-6 secretion and microRNA-181b (miR-181b) expression were
      inversely correlated following LPS stimulation. We also demonstrated that miR
      181b targeting the 3'-UTR of IL-6 transcripts and up-regulation of miR-181b was
      associated with NF-kB. We further demonstrated that up-regulation of miR-181b in
      response to LPS was required for inducing IL-6 tolerance in macrophage. Our
      results suggested that the post-transcriptional control mediated by miR-181b
      could be involved in fine tuning the critical level of IL-6 expression in
      endotoxin tolerance. 

PMID- 25762866
TI  - Towards further defining the proteome of mouse saliva.
AB  - BACKGROUND: Knowledge of the mouse salivary proteome is not well documented and
      as a result, very limited. Currently, several salivary proteins remain
      unidentified and for some others, their function yet to be determined. The goal
      of the present study is to utilize mass spectrometry analysis to widen our
      knowledge of mouse salivary proteins, and through extensive database searches,
      provide further insight into the array of proteins that can be found in saliva. A
      comprehensive mouse salivary proteome will also facilitate the development of
      mouse models to study specific biomarkers of many human diseases. RESULTS:
      Individual saliva samples were collected from male and female mice, and later
      pooled according to sex. Two pools of saliva from female mice (2 samples/pool)
      and 2 pools of saliva from male mice were used for analysis utilizing high
      performance liquid chromatograph mass spectrometry (nano-RPLC-MS/MS). The
      resulting datasets identified 345 proteins: 174 proteins were represented in
      saliva obtained from both sexes, as well as 82 others that were more female
      specific and 89 that were more male specific. Of these sex linked proteins,
      twelve were identified as exclusively sex-limited; 10 unique to males and 2
      unique to females. Functional analysis of the 345 proteins identified 128
      proteins with catalytic activity characteristics; indicative of proteins involved
      in digestion, and 35 proteins associated with stress response, host defense, and
      wound healing functions. Submission of the list of 345 proteins to the BioMart
      data mining tool in the Ensembl database further allowed us to identify a total
      of 283 orthologous human genes, of which, 131 proteins were recently reported to
      be present in the human salivary proteome. CONCLUSIONS: The present study is the
      most comprehensive list to date of the proteins that constitute the mouse
      salivary proteome. The data presented can serve as a useful resource for
      identifying potentially useful biomarkers of human health and disease.

PMID- 25762868
TI  - "Role of the adipocyte hormone leptin in cardiovascular diseases - a study from
      Chennai based Population".
AB  - BACKGROUND: Obesity is currently regarded as a pro-inflammatory condition during
      which leptin (Ob gene product) might act as a risk factor for Cardiovascular
      Diseases (CVD) including Acute Myocardial Infarction (AMI). There is a marked
      increase in circulating leptin concentrations and inflammatory markers such as
      Tumor Necrosis Factor-alpha (TNF-alpha) in AMI patients but still the association
      of leptin with inflammation during AMI is not known. The present study suggest
      that elevated levels of leptin might elicit the risk for CVD by signaling for the
      secretion of inflammatory cytokines especially, TNF-alpha. METHODS: Blood samples
      were collected from 100 CVD subjects diagnosed for AMI immediately after their
      admission to the hospital and serum leptin, insulin, glucose, lipids and
      inflammatory marker such as TNF-alpha were measured. 5 ml random (non-fasting)
      blood was collected from 100 non-CVD (control) subjects and the results obtained
      in case of AMI subjects were compared with that of the control subjects. The
      subjects under study included both men and women belonging to the age group of 35
      - 75 and they were classified based on their BMI as normal weight, overweight and
      obese. RESULTS: Circulating levels of leptin are found to be elevated in obese
      control subjects and in patients with AMI irrespective of their Body Mass Index
      (BMI). In addition, leptin is also found to be positively correlated to serum
      triglycerides, insulin and TNF-alpha in AMI subjects. MANOVA analysis suggests
      that leptin might influence the synthesis of insulin and TNF-alpha. This is the
      first report relating leptin to TNF-alpha in Chennai based population, India.
      CONCLUSIONS: Hyperleptinemia might act as a risk marker for AMI. The present
      study suggests that at elevated levels, leptin may favor atherosclerosis by
      promoting the synthesis of TNF-alpha and insulin. However, our report warrants
      further investigation both in vitro and in vivo to determine the exact mechanism
      behind the pro-atherogenic role of leptin. The observed positive correlation
      between leptin and BMI in both AMI and control subjects suggests that obese
      subjects manifest leptin resistance and hence, they possess a greater risk for
      the incidence of CVD.

PMID- 25762867
TI  - Global assays and the management of oral anticoagulation.
AB  - Coagulation tests range from global or overall tests to assays specific to
      individual clotting factors and their inhibitors. Whether a particular test is
      influenced by an oral anticoagulant depends on the principle of the test and the
      type of oral anticoagulant. Knowledge on coagulation tests applicable in
      monitoring status and reversal of oral anticoagulation is a prerequisite when
      studying potential reversal agents or when managing anticoagulation in a clinical
      setting. Specialty tests based on the measurement of residual activated factor X
      (Xa) or thrombin activity, e.g., are highly effective for determining the
      concentration of the new generation direct factor Xa- and thrombin inhibitors,
      but these tests are unsuitable for the assessment of anticoagulation reversal by
      non-specific prohemostatic agents like prothrombin complex concentrate (PCC) and
      recombinant factor VIIa (FVIIa). Global coagulation assays, in this respect, seem
      more appropriate. This review evaluates the current status on the applicability
      of the global coagulation assays PT, APTT, thrombin generation and
      thromboelastography in the management of oral anticoagulation by vitamin K
      antagonists and the direct factor Xa and thrombin inhibitors. Although all global
      tests are influenced by both types of anticoagulants, not all tests are useful
      for monitoring anticoagulation and reversal thereof. Many (pre)analytical
      conditions are of influence on the assay readout, including the oral
      anticoagulant itself, the concentration of assay reagents and the presence of
      other elements like platelets and blood cells. Assay standardization, therefore,
      remains an issue of importance. 

PMID- 25762869
TI  - Safety of a dose-escalated pre-workout supplement in recreationally active
      females.
AB  - BACKGROUND: Pre-workout supplements (PWS) have increased in popularity among
      athletic populations for their purported ergogenic benefits. Most PWS contain a
      "proprietary blend" of several ingredients, such as caffeine, beta-alanine, and
      nitrate in undisclosed dosages. Currently, little research exists on the safety
      and potential side effects of chronic consumption of PWS, and even less so
      involving female populations. Therefore, the purpose of the present study was to
      examine the safety of consuming a dose-escalated PWS over a 28-day period among
      active adult females. METHODS: 34 recreationally active, adult females (27.1 +/-
      5.4 years, 165.2 +/- 5.7 cm, 68.2 +/- 16.0 kg) participated in this study.
      Participants were randomly assigned to consume either 1 (G1) or 2 (G2) servings
      of a PWS daily or remain unsupplemented (CRL) for a period of 28 days. All were
      instructed to maintain their habitual dietary and exercise routines for the
      duration of the study. Fasting blood samples, as well as resting blood pressure
      and heart rate, were taken prior to and following the supplementation period.
      Samples were analyzed for hematological and clinical chemistry panels, including
      lipids. RESULTS: Significant (p < 0.05) group by time interactions were present
      for absolute monocytes (CRL -0.10 +/- 0.10; G1 + 0.03 +/- 0.13; G2 + 0.01 +/-
      0.12*10E3/uL), MCH (CRL -0.13 +/- 0.46; G1 + 0.36 +/- 0.52; G2 -0.19 +/- 0.39
      pg), creatinine (CRL 0.00 +/- 0.05; G1 -0.06 +/- 0.13; G2 -0.14 +/- 0.08 mg/dL),
      eGFR (CRL -0.69 +/- 5.97; G1 + 6.10 +/- 15.89; G2 + 14.63 +/- 7.11 mL/min/1.73),
      and total cholesterol (CRL -2.44 +/- 13.63; G1 + 14.40 +/- 27.32; G2 -10.38 +/-
      15.39 mg/dL). Each of these variables remained within the accepted physiological
      range. No other variables had significant interactions. CONCLUSION: The present
      study confirms the hypothesis that a PWS containing caffeine, beta-alanine, and
      nitrate will not cause abnormal changes in hematological markers or resting vital
      signs among adult females. Although there were statistically significant (p <
      0.05) group by time interactions for absolute monocytes, MCH, creatinine, eGFR,
      and total cholesterol, all of the results remained well within accepted
      physiological ranges and were not clinically significant. In sum, it appears as
      though daily supplementation with up to 2 servings of the PWS under
      investigation, over an interval of 28 days, did not adversely affect markers of
      clinical safety among active adult females.

PMID- 25762870
TI  - Characterizing the impact of development on the dose-exposure-response
      relationship: challenge or opportunity?

PMID- 25762872
TI  - Propylene glycol toxicity in children.
AB  - Propylene glycol (PG) is a commonly used solvent for oral, intravenous, and
      topical pharmaceutical agents. Although PG is generally considered safe, when
      used in high doses or for prolonged periods, PG toxicity can occur. Reported
      adverse effects from PG include central nervous system (CNS) toxicity,
      hyperosmolarity, hemolysis, cardiac arrhythmia, seizures, agitation, and lactic
      acidosis. Patients at risk for toxicity include infants, those with renal or
      hepatic insuficiency, epilepsy, and burn patients receiving extensive dermal
      applications of PG containing products. Laboratory monitoring of PG levels,
      osmolarity, lactate, pyruvate, bicarbonate, creatinine, and anion gap can assist
      practitioners in making the diagnosis of PG toxicity. Numerous studies and case
      reports have been published on PG toxicity in adults. However, very few have been
      reported in pediatric patient populations. A review of the literature is
      presented. 

PMID- 25762873
TI  - Proton pump inhibitor prescribing patterns in newborns and infants.
AB  - OBJECTIVES: In 2011, the Food and Drug Administration (FDA) approved intravenous
      esomeprazole 0.5 mg/day for children aged >1 month and oral esomeprazole for
      infants aged 1 month to <1 year at doses of 2.5, 5, and 10 mg based on weight.
      Prior to 2011, proton pump inhibitors (PPIs) were not approved for use in infants
      aged <1 year. This study determined PPI usage rates prior to the FDA approval
      among newborns and infants in both the inpatient and outpatient settings and
      compared PPI and histamine-2 receptor antagonist (H2RA) usage in the inpatient
      setting. METHODS: We conducted a retrospective analysis of PPI prescribing
      patterns for newborns and infants from 2003 to 2008 using data from the Premier
      Perspective Inpatient Hospital Database and the PharMetrics Patient-Centric
      Database for inpatient and outpatient data, respectively. PPI use and diagnoses
      were determined from clinical and charge records from more than 500 hospitals.
      Descriptive statistics were used to summarize the findings. RESULTS: Our analysis
      showed that PPIs were prescribed for approximately 5000 newborns (0.13%) and
      15,000 infants (2.65%) each year in the hospital setting and 1.6% of newborns and
      infants, as a group, in the outpatient setting. Newborns and infants receiving
      PPIs most often had diagnoses of gastroesophageal reflux disease (GERD) and were
      generally prescribed an adult PPI dose, although the actual dose administered
      could not be substantiated. CONCLUSIONS: Although no PPI was approved by the FDA
      for patients aged <1 year at the time of this study, results of this analysis
      indicate that PPIs were commonly prescribed for newborns and infants, mostly in
      hospital, but also in outpatient settings. Most PPIs were prescribed for infants
      with a diagnosis of GERD.

PMID- 25762871
TI  - Developmental pharmacokinetics in pediatric populations.
AB  - Information on drug absorption and disposition in infants and children has
      increased considerably over the past 2 decades. However, the impact of specific
      age-related effects on pharmacokinetics, pharmacodynamics, and dose requirements
      remains poorly understood. Absorption can be affected by the differences in
      gastric pH and stomach emptying time that have been observed in the pediatric
      population. Low plasma protein concentrations and a higher body water composition
      can change drug distribution. Metabolic processes are often immature at birth,
      which can lead to a reduced clearance and a prolonged half-life for those drugs
      for which metabolism is a significant mechanism for elimination. Renal excretion
      is also reduced in neonates due to immature glomerular filtration, tubular
      secretion, and reabsorption. Limited data are available on the pharmacodynamic
      behavior of drugs in the pediatric population. Understanding these age effects
      provide a mechanistic way to identify initial doses for the pediatric population.
      The various factors that impact pharmacokinetics and pharmacodynamics mature
      towards adult values at different rates, thus requiring continual modification of
      drug dose regimens in neonates, infants, and children. In this paper, the age
      related changes in drug absorption, distribution, metabolism, and elimination in
      infants and children are reviewed, and the age-related dosing regimens for this
      population are discussed. 

PMID- 25762874
TI  - Medication adsorption into contemporary extracorporeal membrane oxygenator
      circuits.
AB  - OBJECTIVE: This study was conducted to evaluate the amount of medication adsorbed
      into extracorporeal membrane oxygenation (ECMO) circuits with a polymethylpentane
      membrane oxygenator and heparin-coated polyvinyl chloride tubing. METHODS: An
      ECMO circuit with the aforementioned components was set up ex vivo and primed
      with expired blood. Midazolam, lorazepam, morphine, and fentanyl were
      administered to the circuit. Fifteen minutes after medication administration, 60
      mL of blood were removed and stored in a 60-mL syringe to serve as a control.
      Medication levels were drawn from the ECMO circuit (test) and control syringe
      (control) 15 minutes, 24 hours, and 48 hours after the medications were
      administered. ECMO circuit medication levels were compared to their corresponding
      syringe control medication levels. Descriptive statistics were used to determine
      the percentage of medication remaining in the blood and compare it to the control
      value. RESULTS: Except for morphine, there was a large decline in medication
      levels over the 48-hour period. Compared to control values, 17.2% of midazolam,
      41.3% of lorazepam, 32.6% of fentanyl, and 102% of morphine remained in the ECMO
      circuit. CONCLUSION: Despite the use of newer components in ECMO circuits, a
      large quantity of medication is adsorbed into the ECMO circuit. Midazolam,
      lorazepam, and fentanyl all showed reductions in medication levels greater than
      50%. Morphine may have advantages for patients on ECMO, as its concentration does
      not appear to be affected.

PMID- 25762875
TI  - Evaluation of Off-label Prescribing at a Children's Rehabilitation Center.
AB  - OBJECTIVE: This study was developed to evaluate the incidence of off-label
      prescribing at a pediatric rehabilitation center. Secondary objectives were to
      describe the medications, patient age groups, and diagnoses most often associated
      with off-label prescribing. METHODS: This was a prospective observational study
      conducted at an academic, inpatient children's rehabilitation center from
      November 11, 2011, to April 1, 2012. Patients younger than 16 years of age who
      received at least 1 prescription medication were included. Data were collected
      from the patients' electronic medical records. RESULTS: A total of 240
      medications orders were placed during the study, with 57% written off-label.
      Thirty-five patients (88%) received at least 1 off-label medication. Forty-nine
      percent of the orders were for patients younger than the approved range, with 48%
      written for an unapproved indication, 2% for an alternative route of
      administration, and 1% for an unapproved age and indication. Children 2 to 12
      years of age received 40% of the off-label orders, followed by adolescents with
      37%. The therapeutic classes most often prescribed off-label were central nervous
      system agents and anti-infectives. CONCLUSION: Off-label prescribing was found in
      the majority of children receiving rehabilitative services, a rate as high or
      higher than that reported in pediatric acute care or clinic settings. The
      medications prescribed off-label most often were central nervous system agents,
      reflecting the need to study medications in the chronic rehabilitation population
      to optimize function in children with brain or spinal cord injury.

PMID- 25762876
TI  - Optimizing pediatric esmolol dosing using computerized practitioner order entry.
AB  - OBJECTIVES: The aims of this study were to 1) describe the cardiovascular dose
      response of esmolol and dose-limiting adverse effects in pediatric patients; 2)
      assess an institutional guideline for protocol adherence, efficacy, and
      achievement of therapeutic targets for pediatric patients with tachyarrhythmias
      or systemic hypertension; and 3) revise the protocol accordingly. METHODS: In
      this prospective study, pediatric/neonatal subjects were identified using a
      medication utilization report in the electronic medical record and treated with
      esmolol for blood pressure or rhythm control at Rady Children's Hospital San
      Diego between November 1, 2012, and February 28, 2013. Inclusion criteria
      required subjects to be under intensive care and have bedside telemetry
      monitoring. Data collection consisted of patient demographic information,
      administration history of esmolol, concurrent administration of other
      cardiovascular medications, patient cardiovascular goals, and vital signs.
      RESULTS: A total of 8 subjects representing 10 administrations of esmolol were
      included in the study. Whereas esmolol was found to be safe and effective overall
      for control of hypertension and tachyarrhythmia, protocol adherence was poor,
      leading to subtherapeutic dosing schemes, dose changes prior to achievement of
      presumed steady-state pharmacokinetics, and erratic dosing to target effect.
      CONCLUSIONS: After the review, the data were revealed at a program-wide
      conference and consensus was reached on a new, data-driven protocol. As a result
      of this quality improvement initiative, the new protocol provides more precise
      dosing and clearly delineated therapeutic targets and is designed to reflect
      specific esmolol pharmacokinetics. The effort emphasizes the need to construct
      foundations for follow-up quality improvement efforts in intensive care
      pharmacology.

PMID- 25762877
TI  - Hemolytic anemia following rasburicase administration: a review of published
      reports.
AB  - Tumor lysis syndrome (TLS) is a potentially lethal complication of anticancer
      treatment. It is caused by the rapid death of malignant cells after initiation of
      cytotoxic therapy and is typically observed in patients with bulky or highly
      proliferative malignancies. Currently, rasburicase is one of the recommended
      therapies for this oncologic emergency. Although this drug is generally well
      tolerated among patients, there have been several reports of hemolytic anemia
      following rasburicase infusions. With drug-induced hemolytic anemia, the
      condition usually resolves shortly after the offending agent is discontinued.
      However, anemia that is prolonged or severe can lead to problems such as
      splenomegaly and rapid heart rate. This paper will review primary literature
      identified through PubMed, International Pharmaceutical Abstracts, and Embase
      concerning the incidence of hemolytic anemia with rasburicase use. From the
      available data, the occurrence of hemolytic anemia will be discussed. 

PMID- 25762878
TI  - Enteral topiramate in a pediatric patient with refractory status epilepticus: a
      case report and review of the literature.
AB  - We describe the use of topiramate in a healthy 12-year-old (88-kg) male who
      developed refractory generalized convulsive status epilepticus. Seizures
      persisted despite aggressive use of benzodiazepines (intravenous lorazepam; oral
      clorazepate), barbiturates (i.e., phenobarbital, pentobarbital), and hydantoins.
      The child's seizures were controlled with nasogastrically administered topiramate
      in doses up to 500 mg twice daily (11.4 mg/kg/day). The patient did not display
      any clinical or laboratory signs of metabolic acidosis while receiving
      topiramate. Topiramate should be considered as a treatment option in refractory
      status epilepticus. 

PMID- 25762880
TI  - Pediatric news.

PMID- 25762879
TI  - Severe Malaria Complicated by G6PD Deficiency in a Pediatric Tanzanian Immigrant.
AB  - Approximately 1,500 cases of malaria are diagnosed in the United States each
      year. Most cases are travelers and immigrants returning from parts of the world
      where malaria transmission occurs. Malaria is the most frequent cause of systemic
      febrile illness without localizing symptoms in travelers returning from the
      developing world, so vigilance by providers is needed when evaluating patients
      returning from areas in which malaria is endemic. Despite the availability of
      effective treatment, malaria still accounts for more than 1 million deaths per
      year worldwide, with rates being disproportionately high in young children under
      the age of 5. We present the case of a 4-year-old refugee who emigrated from
      Tanzania with severe malaria due to dual infections of Plasmodium falciparum and
      P. ovale, whose treatment course was complicated by quinidine gluconate
      cardiotoxicity and glucose-6-phosphate dehydrogenase deficiency. 

PMID- 25762881
TI  - de Quervain's tenosynovitis: a review of the rehabilitative options.
AB  - de Quervain's tenosynovitis is an overuse disease that involves a thickening of
      the extensor retinaculum, which covers the first dorsal compartment. A case study
      approach was utilized in this article to demonstrate many of the available
      medical and occupational therapy modalities to treat this condition. A 34-year
      old right hand-dominant female who works in a daycare facility presents with
      radial side wrist pain during lifting activity for the past 4-6 weeks. The
      patient was diagnosed with de Quervain's tenosynovitis and conservative care was
      initiated. Conservative care involved anti-inflammatory medication and
      corticosteroid injections as well as occupational therapy to include splinting,
      activity modification, modalities, manual treatment, and therapeutic exercise.
      Although conservative care assisted the patient with her symptoms initially, she
      returned with increased pain and discomfort after 2 months time. At that point,
      surgery was discussed and performed to release the first dorsal compartment as
      well as the sub-compartment. The patient was provided with a splint
      postoperatively and initiated occupational therapy for edema and scar management,
      therapeutic exercise, and desensitization. Ultimately, the patient was able to
      return to work pain free. 

PMID- 25762883
TI  - Tenosynovitis of the wrist and thumb and carpal tunnel syndrome caused by
      Histoplasma capsulatum: case report and review of the literature.
AB  - A patient presenting with acute carpal tunnel syndrome and swelling and pain in
      the wrist and thumb is presented. An open carpal tunnel release and
      tenosynovectomy were performed with biopsy specimen revealing infection with
      Histoplasma capsulatum. The case is discussed in context of the prior scant
      literature of tenosynovitis of the wrist and hand caused by histoplasmosis. 

PMID- 25762882
TI  - Biomechanical comparison of double grasping repair versus cross-locked cruciate
      flexor tendon repair.
AB  - PURPOSE: This study was conducted to compare the in vitro biomechanical
      properties of tensile strength and gap resistance of a double grasping loop (DGL)
      flexor tendon repair with the established four-strand cross-locked cruciate (CLC)
      flexor tendon repair, both with an interlocking horizontal mattress (IHM)
      epitendinous suture. The hypothesis is that the DGL-IHM method which utilizes two
      looped core sutures, grasping and locking loops, and a single intralesional knot
      will have greater strength and increased gap resistance than the CLC-IHM method.
      METHODS: Forty porcine tendons were evenly assigned to either the DGL-IHM or CLC
      IHM group. The tendon repair strength, 2-mm gap force and load to failure, was
      measured under a constant rate of distraction. The stiffness of tendon repair was
      calculated and the method of repair failure was analyzed. RESULTS: The CLC-IHM
      group exhibited a statistically significant greater resistance to gapping, a
      statistically significant higher load to 2-mm gapping (62.0 N), and load to
      failure (99.7 N) than the DGL-IHM group (37.1 N and 75.1 N, respectively). Ninety
      percent of CLC-IHM failures were a result of knot failure whereas 30 % of the DGL
      IHM group exhibited knot failure. CONCLUSIONS: This study demonstrates that the
      CLC-IHM flexor tendon repair method better resists gapping and has a greater
      tensile strength compared to the experimental DGL-IHM method. The authors believe
      that while the DGL-IHM provides double the number of sutures at the repair site
      per needle pass, this configuration does not adequately secure the loop suture to
      the tendon, resulting in a high percentage of suture pullout and inability to
      tolerate loads as high as those of the CLC-IHM group.

PMID- 25762884
TI  - Subclavius posticus: an anomalous muscle in association with suprascapular nerve
      compression in an athlete.
AB  - Subclavius posticus is a rare anomalous muscle that traverses from the costal
      cartilage of the first rib posterolaterally to the superior border of the
      scapula. We present an athlete who presented with incapacitating suprascapular
      nerve compression associated with a subclavius posticus diagnosed by MRI.
      Symptoms were relieved, and function was restored by decompression of the nerve
      and excision of the anomalous muscle. We present this case to bring awareness of
      the subclavius posticus as an anatomic variant and a potential additional source
      for compression in suprascapular neuropathy. We recommend high-resolution
      magnetic resonance imaging to evaluate cases of isolated suprascapular
      neuropathy. LEVEL OF EVIDENCE: V.

PMID- 25762885
TI  - Evaluation of the Patient-Specific Functional Scale in hand fractures and
      dislocations.
AB  - BACKGROUND: Generic upper extremity disability questionnaires utilize
      standardized items. The Patient-Specific Functional Scale (PSFS) allows the
      patient to identify specific self-reported items. This study evaluated the
      validity of the PSFS to assess outcome in patients with hand fractures or
      dislocations. METHODS: Adults with hand fractures or dislocations, who completed
      hand therapy between January 2012 and January 2013, were eligible for inclusion.
      At the initial and final assessment, each patient was asked to complete the PSFS.
      Each patient identified three items that were difficult or they were unable to
      perform, and the degree of difficulty was ranked from 0 to 10 (able to perform at
      pre-injury level). We excluded patients with an incomplete PSFS. Statistical
      analyses evaluated the relationships between the PSFS and the independent
      variables. RESULTS: There were 63 patients (37 men, 26 women); 21 of the 63
      patients underwent surgery for fracture fixation. The mean duration of hand
      therapy treatment was 2.2 +/- 1.4 months. The mean PSFS scores were as follows:
      initial 3.2 +/- 2.2; final 8.1 +/- 2.2. There was a significant improvement in
      PSFS scores from initial to final assessment (p < 0.001) and a moderate
      correlation (r = 0.3, p = 0.02). There was no statistical difference in PSFS
      scores between men and women or surgery and no surgery. CONCLUSIONS: In these
      patients with hand fractures or dislocations, the PSFS indicated significant
      improvement in function. Using items identified by the patient, the PSFS provides
      a valuable perspective of outcome and may be used in conjunction with generic
      disease-specific questionnaire for assessment of the upper extremity.

PMID- 25762886
TI  - Managing parrot bite injuries to the hand: not just another animal bite.
AB  - Bites and scratches are common injuries, frequently sustained from humans, dogs
      and cats. Exotic pet-related harm however is an important and increasingly
      emerging class of injury. Whilst the principles of prompt and thorough medical
      assessment, antibiotics and potential surgical washout and debridement apply,
      exotic pet wounds require further consideration. Standard antibiotic prophylaxis
      with amoxicillin/clavulanic acid (also known as co-amoxiclav) is not sufficient
      for the pathogens transmitted by parrot bites. We illustrate the importance of
      adequate consideration of microbiological pathogens with a case report of an open
      finger fracture resulting from a parrot bite. We intend this to be a valuable
      resource for healthcare professionals in their effective management of such
      injuries. LEVEL OF EVIDENCE: V.

PMID- 25762887
TI  - Isolated bony metastasis to upper limb from carcinoma of the oesophagus: report
      of three cases.
AB  - Carcinoma of the oesophagus metastasizes to distant sites in approximately one
      third of cases and rarely involves the upper limb bones. We describe three such
      rare cases of isolated metastasis to upper limb bone from oesophageal cancer. 

PMID- 25762888
TI  - Giant acquired periungual fibrokeratoma of the thumb: case report and review.
AB  - Fibrokeratoma is a benign fibrous tumor which usually arises in fingers and toes.
      Tumor size is usually small, around 3-5 mm. We report a giant acquired periungual
      fibrokeratoma of the thumb in this study. The size of the tumor is 40 * 25 * 21
      mm(3). Clinical and histopathological characteristics of acquired fibrokeratoma
      are also reviewed. 

PMID- 25762889
TI  - Bilateral congenital absence of the opponens pollicis muscle: a case report.
AB  - BACKGROUND: Thumb hypoplasia and thenar muscle anomalies are complex congenital
      conditions that are associated with other congenital anomalies or syndromes.
      Congenital absence of the opponens pollicis muscle is very rare and is associated
      with the absence of other muscles. METHODS: A 6-year-old male was referred to our
      clinic with a provisional diagnosis of carpal tunnel syndrome because
      electromyography findings at the referring hospital were consistent with this
      diagnosis. He was unable to oppose his thumbs to his other fingers or grasp
      objects. All physical examination, electromyography, and magnetic resonance
      imaging findings were consistent with bilateral absence of the opponens pollicis
      muscle. RESULTS: The patient underwent bilateral transfer of the extensor indicis
      proprius tendon. At 1 year after surgery, he had satisfactory thumb opposition on
      both sides. CONCLUSIONS: Differentiation between congenital muscle anomalies and
      carpal tunnel syndrome is very important in order to avoid performing unnecessary
      surgical procedures. We present a case of bilateral congenital absence of the
      opponens pollicis muscle, which has not previously been reported, and review the
      literature regarding congenital muscle anomalies of the hand.

PMID- 25762890
TI  - Airbag-induced thumb avulsion: two case reports.
AB  - Although airbags are designed to save lives and protect victims from serious
      injuries, airbag deployment can cause unwanted lesions. In this case report, two
      cases are presented of young women who sustained an important fracture
      dislocation of the first carpometacarpal joint (CMC I joint) caused by airbag
      deployment during a car collision. 

PMID- 25762891
TI  - An alternate graft for staged flexor tendon reconstruction.
AB  - We describe the novel use of semitendinosus as a tendon graft for 2-stage flexor
      digitorum profundus (FDP) reconstruction. To our knowledge, this is the first
      reported use of a hamstring tendon graft in this setting. The FDP of two digits
      were reconstructed in a 30 year-old male who presented 18 years after the
      original injury. The semitendinosus was chosen as a graft as the traditional
      grafts were deemed inappropriate. The result of the operation is convincing, and
      we suggest the semitendinosus tendon to be considered an option for FDP
      reconstruction. 

PMID- 25762892
TI  - Carpometacarpal boss: an unusual cause of extensor tendon ruptures.

PMID- 25762893
TI  - Pollicization of the index finger for radial hypoplasia.
AB  - BACKGROUND: Associated with anomalies such as VACTERL and Fanconi anemia,
      congenital hypoplasia of the thumb has a strong association with radial
      hypoplasia. The majority of patients have bilateral thumb underdevelopment, and
      those that have a unilateral deformity tend to have the right hand more commonly
      affected. In order to gain an opposable thumb, patients with a deficient
      carpometacarpal (CMC) joint, a floating thumb, or complete absence of the thumb
      can benefit with a thumb amputation and a translocation of the index finger
      (pollicization) to the thumb position. This video demonstrates the technical
      steps involved in performing a pollicization procedure in a patient with radial
      hypoplasia. The video is available electronically. METHODS: All procedures
      followed were in accordance with the ethical standards of the responsible
      committee on human experimentation (institutional and national) and with the
      Helsinki Declaration of 1975, as revised in 2008 (5). Informed consent was
      obtained from all individual participants included in the video. The authors
      declare that they have no conflict of interest. RESULTS: Pollicization allows for
      improved functional results in patients with radial hypoplasia. CONCLUSIONS: This
      video has reviewed the essential steps in performing a pollicization procedure in
      patients with radial hypoplasia.

PMID- 25762894
TI  - The trace amine-associated receptor 1 modulates methamphetamine's neurochemical
      and behavioral effects.
AB  - The newly discovered trace amine-associated receptor 1 (TAAR1) has the ability to
      regulate both dopamine function and psychostimulant action. Here, we tested in
      rats the ability of RO5203648, a selective TAAR1 partial agonist, to modulate the
      physiological and behavioral effects of methamphetamine (METH). In experiment 1,
      RO5203468 dose- and time-dependently altered METH-induced locomotor activity,
      manifested as an early attenuation followed by a late potentiation of METH's
      stimulating effects. In experiment 2, rats received a 14-day treatment regimen
      during which RO5203648 was co-administered with METH. RO5203648 dose-dependently
      attenuated METH-stimulated hyperactivity, with the effects becoming more apparent
      as the treatments progressed. After chronic exposure and 3-day withdrawal, rats
      were tested for locomotor sensitization. RO5203648 administration during the
      sensitizing phase prevented the development of METH sensitization. However,
      RO5203648, at the high dose, cross-sensitized with METH. In experiment 3,
      RO5203648 dose-dependently blocked METH self-administration without affecting
      operant responding maintained by sucrose, and exhibited lack of reinforcing
      efficacy when tested as a METH's substitute. Neurochemical data showed that
      RO5203648 did not affect METH-mediated DA efflux and uptake inhibition in
      striatal synaptosomes. In vivo, however, RO5203648 was able to transiently
      inhibit METH-induced accumulation of extracellular DA levels in the nucleus
      accumbens. Taken together, these data highlight the significant potential of
      TAAR1 to modulate METH's neurochemical and behavioral effects. 

PMID- 25762895
TI  - Molecular mechanism of Spinocerebellar Ataxia type 6: glutamine repeat disorder,
      channelopathy and transcriptional dysregulation. The multifaceted aspects of a
      single mutation.
AB  - Spinocerebellar Ataxia type 6 (SCA6) is an autosomal dominant neurodegenerative
      disease characterized by late onset, slowly progressive, mostly pure cerebellar
      ataxia. It is one of three allelic disorders associated to CACNA1A gene, coding
      for the Alpha1 A subunit of P/Q type calcium channel Cav2.1 expressed in the
      brain, particularly in the cerebellum. The other two disorders are Episodic
      Ataxia type 2 (EA2), and Familial Hemiplegic Migraine type 1 (FHM1). These
      disorders show distinct phenotypes that often overlap but have different
      pathogenic mechanisms. EA2 and FHM1 are due to mutations causing, respectively, a
      loss and a gain of channel function. SCA6, instead, is associated with short
      expansions of a polyglutamine stretch located in the cytoplasmic C-terminal tail
      of the protein. This domain has a relevant role in channel regulation, as well as
      in transcription regulation of other neuronal genes; thus the SCA6 CAG repeat
      expansion results in complex pathogenic molecular mechanisms reflecting the
      complex Cav2.1 C-terminus activity. We will provide a short review for an update
      on the SCA6 molecular mechanism. 

PMID- 25762896
TI  - Augmentation of Ca(2+) signaling in astrocytic endfeet in the latent phase of
      temporal lobe epilepsy.
AB  - Astrocytic endfeet are specialized cell compartments whose important homeostatic
      roles depend on their enrichment of water and ion channels anchored by the
      dystrophin associated protein complex (DAPC). This protein complex is known to
      disassemble in patients with mesial temporal lobe epilepsy and in the latent
      phase of experimental epilepsies. The mechanistic underpinning of this
      disassembly is an obvious target of future therapies, but remains unresolved.
      Here we show in a kainate model of temporal lobe epilepsy that astrocytic endfeet
      display an enhanced stimulation-evoked Ca(2+) signal that outlast the Ca(2+)
      signal in the cell bodies. While the amplitude of this Ca(2+) signal is reduced
      following group I/II metabotropic receptor (mGluR) blockade, the duration is
      sustained. Based on previous studies it has been hypothesized that the molecular
      disassembly in astrocytic endfeet is caused by dystrophin cleavage mediated by
      Ca(2+) dependent proteases. Using a newly developed genetically encoded Ca(2+)
      sensor, the present study bolsters this hypothesis by demonstrating long-lasting,
      enhanced stimulation-evoked Ca(2+) signals in astrocytic endfeet. 

PMID- 25762897
TI  - IL-10 regulates adult neurogenesis by modulating ERK and STAT3 activity.
AB  - The adult subventricular zone (SVZ) contains Nestin+ progenitors that
      differentiate mainly into neuroblasts. Our previous data showed that interleukin
      10 (IL-10) regulates SVZ adult neurogenesis by up-regulating the expression of
      pro-neural genes and modulating cell cycle exit. Here we addressed the specific
      mechanism through which IL-10 carries out its signaling on SVZ progenitors. We
      found that, in vitro and in vivo, IL-10 targets Nestin+ progenitors and activates
      the phosphorylation of ERK and STAT3. The action of IL-10 on Nestin+ progenitors
      is reversed by treatment with a MEK/ERK inhibitor, thus restoring neurogenesis to
      normal levels. Silencing STAT3 expression by lentiviral vectors also impaired
      neurogenesis by blocking the effects of IL-10. Our findings unveil ERK and STAT3
      as effectors of IL-10 in adult SVZ neurogenesis. 

PMID- 25762898
TI  - Adolescent maturation of inhibitory inputs onto cingulate cortex neurons is cell
      type specific and TrkB dependent.
AB  - The maturation of inhibitory circuits during adolescence may be tied to the onset
      of mental health disorders such as schizophrenia. Neurotrophin signaling likely
      plays a critical role in supporting inhibitory circuit development and is also
      implicated in psychiatric disease. Within the neocortex, subcircuits may mature
      at different times and show differential sensitivity to neurotrophin signaling.
      We measured miniature inhibitory and excitatory postsynaptic currents (mIPSCs and
      mEPSCs) in Layer 5 cell-types in the mouse anterior cingulate (Cg) across the
      periadolescent period. We differentiated cell-types mainly by Thy1 YFP transgene
      expression and also retrobead injection labeling in the contralateral Cg and
      ipsilateral pons. We found that YFP- neurons and commissural projecting neurons
      had lower frequency of mIPSCs than neighboring YFP+ neurons or pons projecting
      neurons in juvenile mice (P21-25). YFP- neurons and to a lesser extent
      commissural projecting neurons also showed a significant increase in mIPSC
      amplitude during the periadolescent period (P21-25 vs. P40-50), which was not
      seen in YFP+ neurons or pons projecting neurons. Systemic disruption of tyrosine
      kinase receptor B (TrkB) signaling during P23-50 in TrkBF616A mice blocked
      developmental changes in mIPSC amplitude, without affecting miniature excitatory
      post synaptic currents (mEPSCs). Our data suggest that the maturation of
      inhibitory inputs onto Layer 5 pyramidal neurons is cell-type specific. These
      data may inform our understanding of adolescent brain development across species
      and aid in identifying candidate subcircuits that may show greater vulnerability
      in mental illness.

PMID- 25762900
TI  - Ontogenesis of NADPH-diaphorase positive neurons in guinea pig neocortex.
AB  - In mammalian cerebrum there exist two distinct types of interneurons expressing
      nitric oxide synthase (NOS). Type I neurons are large in size and exhibit heavy
      nicotinamide adenine dinucleotide phosphate diaphorase (NADPH-d) histochemical
      reaction, while type II cells are small with light NADPH-d reactivity. The time
      of origin of these cortical neurons relative to corticogenesis remains largely
      unclear among mammals. Here we explored this issue in guinea pigs using cell
      birth-dating and double-labeling methods. Bromodeoxyuridine (BrdU) pulse-chasing
      (2 doses at 50 mg/kg, 12 h apart) was given to time-pregnant mothers, followed by
      quantification of NADPH-d/BrdU colocalization in the parietal and temporal
      neocortex in offspring at postnatal day 0 (P0), P30 and P60. Type I neurons were
      partially colabeled with BrdU at P0, P30 and P60 following pulse-chasing at
      embryonic day 21 (E21), E28 and E35, varied from 2-11.3% of total population of
      these neurons for the three time groups. Type II neurons were partially colabeled
      for BrdU following pulse-chasing at E21, E28, E35 and E42 at P0 (8.6%-16.5% of
      total population for individual time groups). At P60, type II neurons were found
      to co-express BrdU (4.8-11.3% of total population for individual time groups)
      following pulse-chasing at E21, E28, E35, E42, E49, E56 and E60/61. These results
      indicate that in guinea pigs type I neurons are generated during early
      corticogenesis, whereas type II cells are produced over a wide prenatal time
      window persisting until birth. The data also suggest that type II nitrinergic
      neurons may undergo a period of development/differentiation, for over 1 month,
      before being NADPH-d reactive. 

PMID- 25762901
TI  - The biological role of the medial olivocochlear efferents in hearing: separating
      evolved function from exaptation.
AB  - Cochlear outer hair cells (OHCs) are remarkable, mechanically-active receptors
      that determine the exquisite sensitivity and frequency selectivity characteristic
      of the mammalian auditory system. While there are three to four times as many
      OHCs compared with inner hair cells, OHCs lack a significant afferent innervation
      and, instead, receive a rich efferent innervation from medial olivocochlear (MOC)
      efferent neurons. Activation of the MOC has been shown to exert a considerable
      suppressive effect over OHC activity. The precise function of these efferent
      tracts in auditory behavior, however, is the matter of considerable debate. The
      most frequent functions assigned to the MOC tracts are to protect the cochlea
      from traumatic damage associated with intense sound and to aid the detection of
      signals in noise. While considerable evidence shows that interruption of MOC
      activity exacerbates damage due to high-level sound exposure, the well
      characterized MOC physiology and evolutionary studies do not support such a role.
      Instead, a MOC protective effect is well explained as being a byproduct of the
      suppressive nature of MOC action on OHC mechanical behavior. A role in the
      enhancement of signals in noise backgrounds, on the other hand, is well supported
      by (1) an extensive physiological literature (2) examination of naturally
      occurring environmental acoustic conditions (3) recent data from multiple
      laboratories showing that the MOC plays a significant role in auditory selective
      attention by suppressing the response to unattended or ignored stimuli. This
      presentation will argue that, based on the extant literature combining the
      suppression of background noise through MOC-mediated rapid adaptation (RA) with
      the suppression of non-attended signals, in concert with the corticofugal
      pathways descending from the auditory cortex, the MOC system has one evolved
      function-to increase the signal-to-noise ratio, aiding in the detection of target
      signals. By contrast, the MOC system role in reducing noise damage and the
      effects of aging in the cochlea may well represent an exaptation, or evolutionary
      "spandrel". 

PMID- 25762899
TI  - GDNF-based therapies, GDNF-producing interneurons, and trophic support of the
      dopaminergic nigrostriatal pathway. Implications for Parkinson's disease.
AB  - The glial cell line-derived neurotrophic factor (GDNF) is a well-established
      trophic agent for dopaminergic (DA) neurons in vitro and in vivo. GDNF is
      necessary for maintenance of neuronal morphological and neurochemical phenotype
      and protects DA neurons from toxic damage. Numerous studies on animal models of
      Parkinson's disease (PD) have reported beneficial effects of GDNF on
      nigrostriatal DA neuron survival. However, translation of these observations to
      the clinical setting has been hampered so far by side effects associated with the
      chronic continuous intra-striatal infusion of recombinant GDNF. In addition,
      double blind and placebo-controlled clinical trials have not reported any
      clinically relevant effect of GDNF on PD patients. In the past few years,
      experiments with conditional Gdnf knockout mice have suggested that GDNF is
      necessary for maintenance of DA neurons in adulthood. In parallel, new
      methodologies for exogenous GDNF delivery have been developed. Recently, it has
      been shown that a small population of scattered, electrically interconnected,
      parvalbumin positive (PV+) GABAergic interneurons is responsible for most of the
      GDNF produced in the rodent striatum. In addition, cholinergic striatal
      interneurons appear to be also involved in the modulation of striatal GDNF. In
      this review, we summarize current knowledge on brain GDNF delivery, homeostasis,
      and its effects on nigrostriatal DA neurons. Special attention is paid to the
      therapeutic potential of endogenous GDNF stimulation in PD. 

PMID- 25762902
TI  - Performance enhancement in the workplace: why and when healthy individuals should
      disclose their reliance on pharmaceutical cognitive enhancers.
AB  - The use of pharmaceuticals cognitive enhancers (PCE) has been stirring growing
      interest, not only in the scientific domain but also in the popular media, and
      has probably had some increase recently in academic, professional and military
      quarters. So this phenomenon is deemed as a normal procedure aimed at improving
      the performance of an individual as well as the overall standards of an
      organization. Although the vast majority of countries have some kind of
      restrictions to reduce the wide non-medical usage of PCE, these can be overcome
      quite easily. In arguing for our explicit claim that, in many contexts, the use
      of cognitive enhancers should be disclosed-as a moral and socially relevant duty
      we maintain that PCE present typical, or at least not rare, properties. The
      features are the following: (a) the enhancer has acute and/or chronic effects. In
      the first case, shortly after taking the drug the performance is significantly
      better than average; in the second case, there is a growing or lasting effect,
      which, however, is poised to diminish when one stops taking the drug; (b) those
      effects are significant (there is a difference in the outcome considered between
      taking and not taking the drug) and sometimes dramatic; and (c) a third feature,
      not directly related to enhancers as such, is their varying safety, availability,
      and legal permissibility, which might either induce people to take them or
      refrain them from doing so. We will consider the issue of fairness due to
      "unenhanced" people as well as the potentially dysfunctional social consequences
      of an undisclosed PCE use. 

PMID- 25762903
TI  - What will this do to me and my brain? Ethical issues in brain-to-brain
      interfacing.
AB  - Recent brain-to-brain interfacing studies provide proof of principle for the
      feasibility of various forms of direct information transfer between two brains,
      and may lead to the development of new approaches involving memory, emotions, or
      senses. What makes brain-to-brain interfaces unique is the transfer of
      information representing specific messages directly from one brain to another,
      without involving any activity of the peripheral nervous system or senses. The
      article discusses ethical issues that arise in neural interfacing. The focus is
      on the implications that brain-to-brain interfaces may have on the individual at
      the recipient side. 

PMID- 25762904
TI  - Criticality as a signature of healthy neural systems.

PMID- 25762905
TI  - Visual-auditory integration for visual search: a behavioral study in barn owls.
AB  - Barn owls are nocturnal predators that rely on both vision and hearing for
      survival. The optic tectum of barn owls, a midbrain structure involved in
      selective attention, has been used as a model for studying visual-auditory
      integration at the neuronal level. However, behavioral data on visual-auditory
      integration in barn owls are lacking. The goal of this study was to examine if
      the integration of visual and auditory signals contributes to the process of
      guiding attention toward salient stimuli. We attached miniature wireless video
      cameras on barn owls' heads (OwlCam) to track their target of gaze. We first
      provide evidence that the area centralis (a retinal area with a maximal density
      of photoreceptors) is used as a functional fovea in barn owls. Thus, by mapping
      the projection of the area centralis on the OwlCam's video frame, it is possible
      to extract the target of gaze. For the experiment, owls were positioned on a high
      perch and four food items were scattered in a large arena on the floor. In
      addition, a hidden loudspeaker was positioned in the arena. The positions of the
      food items and speaker were changed every session. Video sequences from the
      OwlCam were saved for offline analysis while the owls spontaneously scanned the
      room and the food items with abrupt gaze shifts (head saccades). From time to
      time during the experiment, a brief sound was emitted from the speaker. The
      fixation points immediately following the sounds were extracted and the distances
      between the gaze position and the nearest items and loudspeaker were measured.
      The head saccades were rarely toward the location of the sound source but to
      salient visual features in the room, such as the door knob or the food items.
      However, among the food items, the one closest to the loudspeaker had the highest
      probability of attracting a gaze shift. This result supports the notion that
      auditory signals are integrated with visual information for the selection of the
      next visual search target. 

PMID- 25762906
TI  - Preferences and beliefs in ingroup favoritism.
AB  - Ingroup favoritism-the tendency to favor members of one's own group over those in
      other groups-is well documented, but the mechanisms driving this behavior are not
      well understood. In particular, it is unclear to what extent ingroup favoritism
      is driven by preferences concerning the welfare of ingroup over outgroup members,
      vs. beliefs about the behavior of ingroup and outgroup members. In this review we
      analyze research on ingroup favoritism in economic games, identifying key gaps in
      the literature and providing suggestions on how future work can incorporate these
      insights to shed further light on when, why, and how ingroup favoritism occurs.
      In doing so, we demonstrate how social psychological theory and research can be
      integrated with findings from behavioral economics, providing new theoretical and
      methodological directions for future research. 

PMID- 25762908
TI  - Estimating cognitive load during self-regulation of brain activity and
      neurofeedback with therapeutic brain-computer interfaces.
AB  - Neurofeedback (NFB) training with brain-computer interfaces (BCIs) is currently
      being studied in a variety of neurological and neuropsychiatric conditions in an
      aim to reduce disorder-specific symptoms. For this purpose, a range of
      classification algorithms has been explored to identify different brain states.
      These neural states, e.g., self-regulated brain activity vs. rest, are separated
      by setting a threshold parameter. Measures such as the maximum classification
      accuracy (CA) have been introduced to evaluate the performance of these
      algorithms. Interestingly enough, precisely these measures are often used to
      estimate the subject's ability to perform brain self-regulation. This is
      surprising, given that the goal of improving the tool that differentiates between
      brain states is different from the aim of optimizing NFB for the subject
      performing brain self-regulation. For the latter, knowledge about mental
      resources and work load is essential in order to adapt the difficulty of the
      intervention accordingly. In this context, we apply an analytical method and
      provide empirical data to determine the zone of proximal development (ZPD) as a
      measure of a subject's cognitive resources and the instructional efficacy of NFB.
      This approach is based on a reconsideration of item-response theory (IRT) and
      cognitive load theory for instructional design, and combines them with the CA
      curve to provide a measure of BCI performance. 

PMID- 25762907
TI  - Improvement in precision grip force control with self-modulation of primary motor
      cortex during motor imagery.
AB  - Motor imagery (MI) has shown effectiveness in enhancing motor performance. This
      may be due to the common neural mechanisms underlying MI and motor execution
      (ME). The main region of the ME network, the primary motor cortex (M1), has been
      consistently linked to motor performance. However, the activation of M1 during
      motor imagery is controversial, which may account for inconsistent rehabilitation
      therapy outcomes using MI. Here, we examined the relationship between
      contralateral M1 (cM1) activation during MI and changes in sensorimotor
      performance. To aid cM1 activity modulation during MI, we used real-time fMRI
      neurofeedback-guided MI based on cM1 hand area blood oxygen level dependent
      (BOLD) signal in healthy subjects, performing kinesthetic MI of pinching. We used
      multiple regression analysis to examine the correlation between cM1 BOLD signal
      and changes in motor performance during an isometric pinching task of those
      subjects who were able to activate cM1 during motor imagery. Activities in
      premotor and parietal regions were used as covariates. We found that cM1 activity
      was positively correlated to improvements in accuracy as well as overall
      performance improvements, whereas other regions in the sensorimotor network were
      not. The association between cM1 activation during MI with performance changes
      indicates that subjects with stronger cM1 activation during MI may benefit more
      from MI training, with implications toward targeted neurotherapy. 

PMID- 25762909
TI  - Beliefs and social behavior in a multi-period ultimatum game.
AB  - We conduct a multi-period ultimatum game in which we elicit players' beliefs.
      Responders do not predict accurately the amount that will be offered to them, and
      do not get better in their predictions over time. At the individual level we see
      some effect of the mistake in expectations in the previous period on the
      responder's expectation about the offer in the current period, but this effect is
      relatively small. The proposers' beliefs about the minimum amount that responders
      will accept is significantly higher than the minimum amount responders believe
      will be accepted by other responders. The proposer's belief about the minimal
      acceptable offer does not change following a rejection. Nevertheless, the
      proposer's offer in the next period does increase following a rejection. The
      probability of rejection increases when the responder has higher expectations
      about the amount that will be offered to him or higher beliefs about the minimal
      amount that other responders will accept. 

PMID- 25762910
TI  - Effects of optimism on motivation in rats.
AB  - In humans, optimism is a cognitive construct related to motivation; optimists
      exert effort, whereas pessimists disengage from effort. In this study, using a
      recently developed ambiguous-cue interpretation (ACI) paradigm we took the unique
      opportunity to investigate whether "optimism" as a trait is correlated with
      motivation in rodents. In a series of ACI tests (cognitive bias screening, CBS),
      we identified rats displaying "pessimistic" and "optimistic" traits.
      Subsequently, we investigated the trait differences in the motivation of these
      rats to gain reward and to avoid punishment using a progressive ratio (PR)
      schedule of reinforcement paradigm. Although "optimistic" and "pessimistic"
      animals did not differ in their motivation to avoid punishment, the "optimistic"
      rats were significantly more motivated to gain reward than their "pessimistic"
      conspecifics. For the first time, we showed an association between cognitive
      judgment bias and motivation in an animal model. Because both investigated
      processes are closely related to mental health and wellbeing, our results may be
      valuable for preclinical modeling of many psychiatric disorders. 

PMID- 25762912
TI  - Personality cannot be predicted from the power of resting state EEG.
AB  - In the present study we asked whether it is possible to decode personality traits
      from resting state EEG data. EEG was recorded from a large sample of subjects (n
      = 289) who had answered questionnaires measuring personality trait scores of the
      five dimensions as well as the 10 subordinate aspects of the Big Five. Machine
      learning algorithms were used to build a classifier to predict each personality
      trait from power spectra of the resting state EEG data. The results indicate that
      the five dimensions as well as their subordinate aspects could not be predicted
      from the resting state EEG data. Finally, to demonstrate that this result is not
      due to systematic algorithmic or implementation mistakes the same methods were
      used to successfully classify whether the subject had eyes open or closed. These
      results indicate that the extraction of personality traits from the power spectra
      of resting state EEG is extremely noisy, if possible at all. 

PMID- 25762911
TI  - Disrupted thalamic resting-state functional networks in schizophrenia.
AB  - The thalamus plays a key role in filtering or gating information and has
      extensive interconnectivity with other brain regions. Recent studies provide
      evidence of thalamus abnormality in schizophrenia, but the resting functional
      networks of the thalamus in schizophrenia is still unclear. We characterize the
      thalamic resting-state networks (RSNs) in 72 patients with schizophrenia and 73
      healthy controls, using a standard seed-based whole-brain correlation. In
      comparison with controls, patients exhibited enhance thalamic connectivity with
      bilateral precentral gyrus, dorsal medial frontal gyrus, middle occipital gyrus,
      and lingual gyrus. Reduced thalamic connectivity in schizophrenia was found in
      bilateral superior frontal gyrus, anterior cingualte cortex, inferior parietal
      lobe, and cerebellum. Our findings question the "disconnectivity model" of
      schizophrenia by showing the over-connected thalamic network during resting state
      in schizophrenia and highlight the thalamus as a key hub in the schizophrenic
      network abnormality. 

PMID- 25762913
TI  - Bodily synchronization and ecological validity: a relevant concern for nonlinear
      dynamical systems theory.

PMID- 25762914
TI  - Mental fatigue induced by prolonged self-regulation does not exacerbate central
      fatigue during subsequent whole-body endurance exercise.
AB  - It has been shown that the mental fatigue induced by prolonged self-regulation
      increases perception of effort and reduces performance during subsequent
      endurance exercise. However, the physiological mechanisms underlying these
      negative effects of mental fatigue are unclear. The primary aim of this study was
      to test the hypothesis that mental fatigue exacerbates central fatigue induced by
      whole-body endurance exercise. Twelve subjects performed 30 min of either an
      incongruent Stroop task to induce a condition of mental fatigue or a congruent
      Stroop task (control condition) in a random and counterbalanced order. Both
      cognitive tasks (CTs) were followed by a whole-body endurance task (ET)
      consisting of 6 min of cycling exercise at 80% of peak power output measured
      during a preliminary incremental test. Neuromuscular function of the knee
      extensors was assessed before and after CT, and after ET. Rating of perceived
      exertion (RPE) was measured during ET. Both CTs did not induce any decrease in
      maximal voluntary contraction (MVC) torque (p = 0.194). During ET, mentally
      fatigued subjects reported higher RPE (mental fatigue 13.9 +/- 3.0, control 13.3
      +/- 3.2, p = 0.044). ET induced a similar decrease in MVC torque (mental fatigue 
      17 +/- 15%, control -15 +/- 11%, p = 0.001), maximal voluntary activation level
      (mental fatigue -6 +/- 9%, control -6 +/- 7%, p = 0.013) and resting twitch
      (mental fatigue -30 +/- 14%, control -32 +/- 10%, p < 0.001) in both conditions.
      These findings reject our hypothesis and confirm previous findings that mental
      fatigue does not reduce the capacity of the central nervous system to recruit the
      working muscles. The negative effect of mental fatigue on perception of effort
      does not reflect a greater development of either central or peripheral fatigue.
      Consequently, mentally fatigued subjects are still able to perform maximal
      exercise, but they are experiencing an altered performance during submaximal
      exercise due to higher-than-normal perception of effort. 

PMID- 25762916
TI  - Recognition memory of neutral words can be impaired by task-irrelevant emotional
      encoding contexts: behavioral and electrophysiological evidence.
AB  - Previous studies on the effects of emotional context on memory for centrally
      presented neutral items have obtained inconsistent results. And in most of those
      studies subjects were asked to either make a connection between the item and the
      context at study or retrieve both the item and the context. When no response for
      the contexts is required, how emotional contexts influence memory for neutral
      items is still unclear. Thus, the present study attempted to investigate the
      influences of four types of emotional picture contexts on recognition memory of
      neutral words using both behavioral and event-related potential (ERP)
      measurements. During study, words were superimposed centrally onto emotional
      contexts, and subjects were asked to just remember the words. During test, both
      studied and new words were presented without the emotional contexts and subjects
      had to make "old/new" judgments for those words. The results revealed that,
      compared with the neutral context, the negative contexts and positive high
      arousing context impaired recognition of words. ERP results at encoding
      demonstrated that, compared with items presented in the neutral context, items in
      the positive and negative high-arousing contexts elicited more positive ERPs,
      which probably reflects an automatic process of attention capturing of high
      arousing context as well as a conscious and effortful process of overcoming the
      interference of high-arousing context. During retrieval, significant FN400
      old/new effects occurred in conditions of the negative low-arousing, positive,
      and neutral contexts but not in the negative high-arousing condition. Significant
      LPC old/new effects occurred in all conditions of context. However, the LPC
      old/new effect in the negative high-arousing condition was smaller than that in
      the positive high-arousing and low-arousing conditions. These results suggest
      that emotional context might influence both the familiarity and recollection
      processes. 

PMID- 25762915
TI  - Love-related changes in the brain: a resting-state functional magnetic resonance
      imaging study.
AB  - Romantic love is a motivational state associated with a desire to enter or
      maintain a close relationship with a specific other person. Functional magnetic
      resonance imaging (fMRI) studies have found activation increases in brain regions
      involved in the processing of reward, motivation and emotion regulation, when
      romantic lovers view photographs of their partners. However, not much is known
      about whether romantic love affects the brain's functional architecture during
      rest. In the present study, resting state functional magnetic resonance imaging
      (rsfMRI) data was collected to compare the regional homogeneity (ReHo) and
      functional connectivity (FC) across an "in-love" group (LG, N = 34, currently
      intensely in love), an "ended-love" group (ELG, N = 34, ended romantic
      relationship recently), and a "single" group (SG, N = 32, never fallen in love).
      Results show that: (1) ReHo of the left dorsal anterior cingulate cortex (dACC)
      was significantly increased in the LG (in comparison to the ELG and the SG); (2)
      ReHo of the left dACC was positively correlated with length of time in love in
      the LG, and negatively correlated with the lovelorn duration since breakup in the
      ELG; (3) FC within the reward, motivation, and emotion regulation network (dACC,
      insula, caudate, amygdala, and nucleus accumbens) as well as FC in the social
      cognition network [temporo-parietal junction (TPJ), posterior cingulate cortex
      (PCC), medial prefrontal cortex (MPFC), inferior parietal, precuneus, and
      temporal lobe] was significantly increased in the LG (in comparison to the ELG
      and SG); (4) in most regions within both networks FC was positively correlated
      with the duration of love in the LG but negatively correlated with the lovelorn
      duration of time since breakup in the ELG. This study provides first empirical
      evidence of love-related alterations in brain functional architecture.
      Furthermore, the results shed light on the underlying neural mechanisms of
      romantic love, and demonstrate the possibility of applying a resting-state fMRI
      approach for investigating romantic love. 

PMID- 25762917
TI  - A neuroanatomical framework for upper limb synergies after stroke.
AB  - Muscle synergies describe common patterns of co- or reciprocal activation that
      occur during movement. After stroke, these synergies change, often in
      stereotypical ways. The mechanism underlying this change reflects damage to key
      motor pathways as a result of the stroke lesion, and the subsequent
      reorganization along the neuroaxis, which may be further detrimental or
      restorative to motor function. The time course of abnormal synergy formation
      seems to lag spontaneous recovery that occurs in the initial weeks after stroke.
      In healthy individuals, motor cortical activity, descending via the corticospinal
      tract (CST) is the predominant driver of voluntary behavior. When the CST is
      damaged after stroke, other descending pathways may be up-regulated to
      compensate. The contribution of these pathways may emerge as new synergies take
      shape at the chronic stage after stroke, as a result of plasticity along the
      neuroaxis. The location of the stroke lesion and properties of the secondary
      descending pathways and their regulation are then critical for shaping the
      synergies in the remaining motor behavior. A consideration of the integrity of
      remaining descending motor pathways may aid in the design of new rehabilitation
      therapies. 

PMID- 25762918
TI  - First-person experience and yoga research: studying neural correlates of an
      intentional practice.

PMID- 25762920
TI  - The next move in neuromodulation therapy: a question of timing.

PMID- 25762919
TI  - Effect of 30 Hz theta burst transcranial magnetic stimulation on the primary
      motor cortex in children and adolescents.
AB  - Fourteen healthy children (13.8 +/- 2.2 years, range 10-16; M:F = 5:9) received
      30 Hz intermittent theta burst transcranial magnetic stimulation (iTBS) with a
      stimulation intensity of 70% of resting motor threshold (RMT) with a total of 300
      (iTBS300) pulses. All volunteers were free of neurologic, psychiatric and serious
      medical illnesses, not taking any neuropsychiatric medications, and did not have
      any contraindications to transcranial magnetic stimulation. Changes in the mean
      amplitudes of motor-evoked potentials from baseline following iTBS were expressed
      as a ratio and assessed from 1 to 10 min (BLOCK1) and 1-30 min (BLOCK2) using
      repeated-measures analysis of variance. All 14 subjects completed iTBS300 over
      the dominant primary motor cortex (M1) without any clinically reported adverse
      events. ITBS300 produced significant M1 facilitation [F (5, 65) = 3.165, p =
      0.01] at BLOCK1 and trend level M1 facilitation at BLOCK2 [F (10, 129) = 1.69, p
      = 0.089]. Although iTBS300 (stimulation duration of 92 s at 70% RMT) delivered
      over M1 in typically developed children was well-tolerated and produced on
      average significant facilitatory changes in cortical excitability, the post
      iTBS300 neurophysiologic response was variable in our small sample. ITBS300
      induced changes may represent a potential neuroplastic biomarker in healthy
      children and those with neuro-genetic or neuro-psychiatric disorders. However, a
      larger sample size is needed to address safety and concerns of response
      variability. 

PMID- 25762921
TI  - Cross-frequency transfer in a stochastically driven mesoscopic neuronal model.
AB  - The brain is known to operate in multiple coexisting frequency bands. Increasing
      experimental evidence suggests that interactions between those distinct bands
      play a crucial role in brain processes, but the dynamical mechanisms underlying
      this cross-frequency coupling are still under investigation. Two approaches have
      been proposed to address this issue. In the first one distinct nonlinear
      oscillators representing the brain rhythms involved are coupled actively
      (bidirectionally), whereas in the second one the oscillators are coupled
      unidirectionally and thus the driving between them is passive. Here we elaborate
      the latter approach by implementing a stochastically driven network of coupled
      neural mass models that operate in the alpha range. This model exhibits a
      broadband power spectrum with 1/f(b) form, similar to those observed
      experimentally. Our results show that such a model is able to reproduce recent
      experimental observations on the effect of slow rocking on the alpha activity
      associated with sleep. This suggests that passive driving can account for cross
      frequency transfer in the brain, as a result of the complex nonlinear dynamics of
      its underlying oscillators. 

PMID- 25762923
TI  - Semantic framework for mapping object-oriented model to semantic web languages.
AB  - The article deals with and discusses two main approaches in building semantic
      structures for electrophysiological metadata. It is the use of conventional data
      structures, repositories, and programming languages on one hand and the use of
      formal representations of ontologies, known from knowledge representation, such
      as description logics or semantic web languages on the other hand. Although
      knowledge engineering offers languages supporting richer semantic means of
      expression and technological advanced approaches, conventional data structures
      and repositories are still popular among developers, administrators and users
      because of their simplicity, overall intelligibility, and lower demands on
      technical equipment. The choice of conventional data resources and repositories,
      however, raises the question of how and where to add semantics that cannot be
      naturally expressed using them. As one of the possible solutions, this semantics
      can be added into the structures of the programming language that accesses and
      processes the underlying data. To support this idea we introduced a software
      prototype that enables its users to add semantically richer expressions into a
      Java object-oriented code. This approach does not burden users with additional
      demands on programming environment since reflective Java annotations were used as
      an entry for these expressions. Moreover, additional semantics need not to be
      written by the programmer directly to the code, but it can be collected from non
      programmers using a graphic user interface. The mapping that allows the
      transformation of the semantically enriched Java code into the Semantic Web
      language OWL was proposed and implemented in a library named the Semantic
      Framework. This approach was validated by the integration of the Semantic
      Framework in the EEG/ERP Portal and by the subsequent registration of the EEG/ERP
      Portal in the Neuroscience Information Framework. 

PMID- 25762922
TI  - Distributed cerebellar plasticity implements generalized multiple-scale memory
      components in real-robot sensorimotor tasks.
AB  - The cerebellum plays a crucial role in motor learning and it acts as a predictive
      controller. Modeling it and embedding it into sensorimotor tasks allows us to
      create functional links between plasticity mechanisms, neural circuits and
      behavioral learning. Moreover, if applied to real-time control of a neurorobot,
      the cerebellar model has to deal with a real noisy and changing environment, thus
      showing its robustness and effectiveness in learning. A biologically inspired
      cerebellar model with distributed plasticity, both at cortical and nuclear sites,
      has been used. Two cerebellum-mediated paradigms have been designed: an
      associative Pavlovian task and a vestibulo-ocular reflex, with multiple sessions
      of acquisition and extinction and with different stimuli and perturbation
      patterns. The cerebellar controller succeeded to generate conditioned responses
      and finely tuned eye movement compensation, thus reproducing human-like
      behaviors. Through a productive plasticity transfer from cortical to nuclear
      sites, the distributed cerebellar controller showed in both tasks the capability
      to optimize learning on multiple time-scales, to store motor memory and to
      effectively adapt to dynamic ranges of stimuli. 

PMID- 25762924
TI  - Sustained response of a clivus chordoma to erlotinib after imatinib failure.
AB  - Chordoma is a rare malignant axial tumour that develops from embryonic remnants
      of the notochord. Surgery and irradiation are the standard initial treatment.
      However, local recurrence is frequent and cytotoxic chemotherapy is inefficient.
      Transient activity of imatinib, a platelet-derived growth factor receptor
      inhibitor, was described in a phase II study. Activity of epidermal growth factor
      receptor (EGFR) inhibitors (erlotinib, gefitinib) has also been shown in a few
      recent case reports. We describe a 68-year-old female in whom clivus chordoma
      recurred after surgery and radiotherapy. The tumour progressed despite imatinib
      treatment. A partial and sustained response (28+ months) was obtained using
      erlotinib, an EGFR inhibitor. Erlotinib should be evaluated in a prospective
      trial investigating new potential therapies against recurrent chordoma. 

PMID- 25762925
TI  - A case of pancreatic intraepithelial neoplasia that was difficult to diagnose
      preoperatively.
AB  - A 63-year-old female patient presented to a local physician with pain in her back
      and epigastric region. An abdominal computed tomography (CT) scan revealed a
      pancreatic tumor, and the patient was referred to our hospital. Multiple imaging
      studies that included ultrasonography (US), CT, MRI, and endoscopic US revealed a
      cystic lesion 3-4 cm in size with node-like projections in the body of the
      pancreas. The distal main pancreatic duct was also found to be dilated.
      Endoscopic retrograde pancreatography revealed an irregular stenosis of the main
      pancreatic duct proximal to the cystic lesion, and malignancy was suspected. The
      patient was preoperatively diagnosed with pancreatic ductal carcinoma concomitant
      with intraductal papillary mucinous carcinoma, and a distal pancreatectomy was
      performed. Rapid pathological diagnosis during surgery revealed positive surgical
      margins for pancreatic intraepithelial neoplasia (PanIN). Further resection was
      performed twice, her surgical margin was positive and total pancreatectomy was
      ultimately conducted. Histopathological findings revealed diffuse microinvasive
      cancerous lesions corresponding to PanIN-2 (moderate dysplasia) to PanIN-3
      (carcinoma in situ) throughout the pancreas. PanIN involves microlesions of the
      ductal epithelium that may precede pancreatic cancer. Ascertaining changes in
      PanIN using images provided by diagnostic modalities such as CT and US is
      challenging. Ductal stenosis and distal cystic lesions resulting from atrophy and
      fibrosis of pancreatic tissue were noted around PanIN. Considering the
      possibility of PanIN, a precancerous lesion during differential diagnosis will
      help to improve early detection and prognosis for patients with pancreatic
      cancer. 

PMID- 25762926
TI  - An unusually heavy heart.
AB  - A 47-year-old female presented with worsening insidious symptoms of
      breathlessness and leg swelling over the last 12 months. Whilst her ECG and chest
      X-ray were relatively unremarkable on admission, an echocardiogram demonstrated a
      large-sized left atrial myxoma. This tumour was resected by the cardiac surgeons
      the next day, with very good postoperative results. The ensuing discussion
      details the anatomy and physiology of myxomas, their epidemiology, clinical
      features, diagnostic investigations and management. 

PMID- 25762927
TI  - Alkali burn treated with 2% rebamipide ophthalmic suspension: a case report.
AB  - A 47-year-old man presented at the Ophthalmology Department of Saku City Asama
      General Hospital complaining of hyperemia and pain after industrial sodium
      hydroxide (approx. 40% concentration) had entered his left eye. With an
      epithelial defect of the bulbar and palpebral conjunctiva, ischemia of the
      inferior third of the limbal conjunctiva, a total corneal epithelial defect and
      mild corneal stromal opacity, the damage was determined as Roper-Hall grade III.
      2% rebamipide ophthalmic suspension, which is used for dry eye disease, was
      administered 4 times a day followed by conventional treatment for serious alkali
      injury. The corneal epithelial defect was resolved, and there were no side
      effects. The effectiveness of 2% rebamipide ophthalmic suspension in both the
      repair and improvement of the damage in the conjunctival and corneal epithelia,
      and its anti-inflammatory effect suggest that it may be an effective treatment
      not only for dry eye disease but also for alkali ocular damage. 

PMID- 25762928
TI  - Unusual case of angle closure glaucoma in a patient with neurofibromatosis type
      1.
AB  - We report the case of a 29-year-old female patient who presented with an acute
      onset of anisocoria, blurred vision, nausea and severe left-sided headache. There
      was no history of trauma, drug abuse, or instillation of topical mydriatic
      compounds. The ocular history was negative for similar events. On presentation,
      her visual acuity was 0.2 in the left and 1.0 in the right eye with a +2.5 dpt
      sph. correction. Slit-lamp examination demonstrated a shallow anterior chamber as
      well as the presence of iris nodules in both eyes. These nodules were identified
      as Lisch nodules as the patient referred to the previous diagnosis as being
      neurofibromatosis type 1. A third nerve palsy was considered, but a brain MRI
      showed normal results. Her ocular motility was normal, but the left pupil was
      mydriatic and poorly reacting to light, with an associated raised intraocular
      pressure (IOP) of 38 mm Hg. An examination of the fellow eye was normal, with the
      IOP measuring 18 mm Hg. Gonioscopy of the right eye showed a narrow angle. On
      further anamnestic investigation, the patient revealed that the pain and the
      blurred vision begun in the morning while she was helping her mother in the
      garden. Finally, after showing the patient a picture of Datura flowers, which she
      recognized immediately, we made the unusual diagnosis of angle closure glaucoma
      by Datura, a well-known toxic plant with mydriatic properties. The patient was
      successfully treated with systemic acetazolamide and topical pilocarpine. 

PMID- 25762929
TI  - Restricted loss of olivocochlear but not vestibular efferent neurons in the
      senescent gerbil (Meriones unguiculatus).
AB  - Degeneration of hearing and vertigo are symptoms of age-related auditory and
      vestibular disorders reflecting multifactorial changes in the peripheral and
      central nervous system whose interplay remains largely unknown. Originating
      bilaterally in the brain stem, vestibular and auditory efferent cholinergic
      projections exert feedback control on the peripheral sensory organs, and modulate
      sensory processing. We studied age-related changes in the auditory and vestibular
      efferent systems by evaluating number of cholinergic efferent neurons in young
      adult and aged gerbils, and in cholinergic trigeminal neurons serving as a
      control for efferents not related to the inner ear. We observed a significant
      loss of olivocochlear (OC) neurons in aged compared to young adult animals,
      whereas the overall number of lateral superior olive (LSO) cells was not reduced
      in aging. Although the loss of lateral and medial olivocochlear (MOC) neurons was
      uniform and equal on both sides of the brain, there were frequency-related
      differences within the lateral olivocochlear (LOC) neurons, where the decline was
      larger in the medial limb of the superior olivary nucleus (high frequency
      representation) than in the lateral limb (middle-to-low frequency
      representation). In contrast, neither the number of vestibular efferent neurons,
      nor the population of motor trigeminal neurons were significantly reduced in the
      aged animals. These observations suggest differential effects of aging on the
      respective cholinergic efferent brainstem systems. 

PMID- 25762930
TI  - Swept-sine noise-induced damage as a hearing loss model for preclinical assays.
AB  - Mouse models are key tools for studying cochlear alterations in noise-induced
      hearing loss (NIHL) and for evaluating new therapies. Stimuli used to induce
      deafness in mice are usually white and octave band noises that include very low
      frequencies, considering the large mouse auditory range. We designed different
      sound stimuli, enriched in frequencies up to 20 kHz ("violet" noises) to examine
      their impact on hearing thresholds and cochlear cytoarchitecture after short
      exposure. In addition, we developed a cytocochleogram to quantitatively assess
      the ensuing structural degeneration and its functional correlation. Finally, we
      used this mouse model and cochleogram procedure to evaluate the potential
      therapeutic effect of transforming growth factor beta1 (TGF-beta1) inhibitors P17
      and P144 on NIHL. CBA mice were exposed to violet swept-sine noise (VS) with
      different frequency ranges (2-20 or 9-13 kHz) and levels (105 or 120 dB SPL) for
      30 min. Mice were evaluated by auditory brainstem response (ABR) and otoacoustic
      emission tests prior to and 2, 14 and 28 days after noise exposure. Cochlear
      pathology was assessed with gross histology; hair cell number was estimated by a
      stereological counting method. Our results indicate that functional and
      morphological changes induced by VS depend on the sound level and frequency
      composition. Partial hearing recovery followed the exposure to 105 dB SPL,
      whereas permanent cochlear damage resulted from the exposure to 120 dB SPL.
      Exposure to 9-13 kHz noise caused an auditory threshold shift (TS) in those
      frequencies that correlated with hair cell loss in the corresponding areas of the
      cochlea that were spotted on the cytocochleogram. In summary, we present mouse
      models of NIHL, which depending on the sound properties of the noise, cause
      different degrees of cochlear damage, and could therefore be used to study
      molecules which are potential players in hearing loss protection and repair. 

PMID- 25762931
TI  - Visuospatial characteristics of an elderly Chinese population: results from the
      WAIS-R block design test.
AB  - Visuospatial deficits have long been recognized as a potential predictor of
      dementia, with visuospatial ability decline having been found to accelerate in
      later stages of dementia. We, therefore, believe that the visuospatial
      performance of patients with mild cognitive impairment (MCI) and dementia (Dem)
      might change with varying visuospatial task difficulties. This study administered
      the Wechsler Adult Intelligence Scale-Revised (WAIS-R) Block Design Test (BDT) to
      determine whether visuospatial ability can help discriminate between MCI patients
      from Dem patients and normal controls (NC). Results showed that the BDT could
      contribute to the discrimination between MCI and Dem. Specifically, simple BDT
      task scores could best distinguish MCI from Dem patients, while difficult BDT
      task scores could contribute to discriminating between MCI and NC. Given the
      potential clinical value of the BDT in the diagnosis of Dem and MCI, normative
      data stratified by age and education for the Chinese elderly population are
      presented for use in research and clinical settings. 

PMID- 25762932
TI  - Citrus aurantium increases seizure latency to PTZ induced seizures in zebrafish
      thru NMDA and mGluR's I and II.
AB  - Epilepsy is a serious neurological condition and pharmacotherapy is not effective
      for all patients and causes serious adverse effects and pharmacokinetic and
      pharmacodynamic interactions. Natural products and ethnobotanical resources can
      help develop new therapeutic options for conditions like epilepsy. In Puerto
      Rico, ethnobotanical resources highlight the anxiolytic properties of a tea like
      preparation made from the leaves of the Citrus aurantium tree or bitter orange.
      Studies performed with essential oils from the peel of the fruit have shown to
      increase seizure latency to pentylenetetrazole (PTZ) and maximal electroshock
      seizure in mice. We characterized the extract composition, and used a model of
      PTZ induces seizures in the zebrafish and a receptor-ligand binding assay to
      determine if this preparation has anticonvulsant properties and its mechanism of
      action. We determined that the aqueous extract made from the leaves of the C.
      aurantium tree contains hesperidin, neohesperidin, and neohesperidin
      dihydrochalcone. Using our zebrafish model, we determined that exposure to the C.
      aurantium 28 mg/mL extract in aquarium water increases seizure latency by 119%
      compared to controls. We ruled out a mechanism involving GABAA receptors using
      the selective antagonist gabazine. We used two approaches to study the role of
      glutamate in the mechanism of the C. aurantium extract. The ligand binding assay
      revealed C. aurantium extracts at concentrations of 0.42 to 5.6 mg/mL
      significantly reduced [(3)H]Glu binding indicating an interaction with glutamate
      receptors, in particular with NMDA receptors and mGluR II. This interaction was
      confirmed with our animal model using selective receptor antagonists and we
      identified an interaction with mGluR I, not observed in the ligand binding
      experiment. These study provide evidence of the anticonvulsant properties of the
      aqueous extract made from the leaves of the C. aurantium tree and a mechanism
      involving NMDA and mGluR's I and II. 

PMID- 25762934
TI  - HIV drug nucleoside reverse transcriptase inhibitors as promising anti
      inflammation therapeutics by targeting P2X7-dependent large pore formation: one
      stone for two birds?

PMID- 25762933
TI  - Drug therapy for the prevention and treatment of bronchopulmonary dysplasia.
AB  - INTRODUCTION: As more infants are surviving at younger gestational ages,
      bronchopulmonary dysplasia (BPD) remains as a frequent neonatal complication
      occurring after preterm birth. The multifactorial nature of the disease process
      makes BPD a challenging condition to treat. While multiple pharmacologic
      therapies have been investigated over the past two decades, there have been
      limited advances in the field. Often multiple therapies are used concurrently
      without clear evidence of efficacy, with potential for significant side effects
      from drug-drug interactions. METHODS: Systematic literature review. CONCLUSION:
      Although there is physiologic rationale for the use of many of these therapies,
      none of them has single-handedly altered the incidence, severity, or progression
      of BPD. Future research should focus on developing clinically significant end
      points (short and long term respiratory assessments), investigating biomarkers
      that accurately predict risk and progression of disease, and creating appropriate
      stratification models of BPD severity. Applying a multi-modal approach to the
      study of new and existing drugs should be the most effective way of establishing
      the optimal prevention and treatment regimens for BPD.

PMID- 25762935
TI  - Non-apoptotic cell death associated with perturbations of macropinocytosis.
AB  - Although macropinocytosis is widely recognized as a distinct form of fluid-phase
      endocytosis in antigen-presenting dendritic cells, it also occurs constitutively
      in many other normal and transformed cell types. Recent studies have established
      that various genetic or pharmacological manipulations can hyperstimulate
      macropinocytosis or disrupt normal macropinosome trafficking pathways, leading to
      accumulation of greatly enlarged cytoplasmic vacuoles. In some cases, this
      extreme vacuolization is associated with a unique form of non-apoptotic cell
      death termed "methuosis," from the Greek methuo (to drink to intoxication). It
      remains unclear whether cell death related to dysfunctional macropinocytosis
      occurs in normal physiological contexts. However, the finding that some types of
      cancer cells are particularly vulnerable to this unusual form of cell death has
      raised the possibility that small molecules capable of altering macropinosome
      trafficking or function might be useful as therapeutic agents against cancers
      that are resistant to drugs that work by inducing apoptosis. Herein we review
      examples of cell death associated with dysfunctional macropinocytosis and
      summarize what is known about the underlying mechanisms. 

PMID- 25762936
TI  - Acceleration of discrete stochastic biochemical simulation using GPGPU.
AB  - For systems made up of a small number of molecules, such as a biochemical network
      in a single cell, a simulation requires a stochastic approach, instead of a
      deterministic approach. The stochastic simulation algorithm (SSA) simulates the
      stochastic behavior of a spatially homogeneous system. Since stochastic
      approaches produce different results each time they are used, multiple runs are
      required in order to obtain statistical results; this results in a large
      computational cost. We have implemented a parallel method for using SSA to
      simulate a stochastic model; the method uses a graphics processing unit (GPU),
      which enables multiple realizations at the same time, and thus reduces the
      computational time and cost. During the simulation, for the purpose of analysis,
      each time course is recorded at each time step. A straightforward implementation
      of this method on a GPU is about 16 times faster than a sequential simulation on
      a CPU with hybrid parallelization; each of the multiple simulations is run
      simultaneously, and the computational tasks within each simulation are
      parallelized. We also implemented an improvement to the memory access and reduced
      the memory footprint, in order to optimize the computations on the GPU. We also
      implemented an asynchronous data transfer scheme to accelerate the time course
      recording function. To analyze the acceleration of our implementation on various
      sizes of model, we performed SSA simulations on different model sizes and
      compared these computation times to those for sequential simulations with a CPU.
      When used with the improved time course recording function, our method was shown
      to accelerate the SSA simulation by a factor of up to 130. 

PMID- 25762937
TI  - An introduction to heart rate variability: methodological considerations and
      clinical applications.

PMID- 25762940
TI  - Sex differences in psychiatric comorbidity and plasma biomarkers for cocaine
      addiction in abstinent cocaine-addicted subjects in outpatient settings.
AB  - There are sex differences in the progression of drug addiction, relapse, and
      response to therapies. Because biological factors participate in these
      differences, they should be considered when using biomarkers for addiction. In
      the current study, we evaluated the sex differences in psychiatric comorbidity
      and the concentrations of plasma mediators that have been reported to be affected
      by cocaine. Fifty-five abstinent cocaine-addicted subjects diagnosed with
      lifetime cocaine use disorders (40 men and 15 women) and 73 healthy controls (48
      men and 25 women) were clinically assessed with the diagnostic interview
      "Psychiatric Research Interview for Substance and Mental Disorders." Plasma
      concentrations of chemokines, cytokines, N-acyl-ethanolamines, and 2-acyl
      glycerols were analyzed according to history of cocaine addiction and sex,
      controlling for covariates age and body mass index (BMI). Relationships between
      these concentrations and variables related to cocaine addiction were also
      analyzed in addicted subjects. The results showed that the concentrations of
      chemokine (C-C motif) ligand 2/monocyte chemotactic protein-1 (CCL2/MCP-1) and
      chemokine (C-X-C motif) ligand 12/stromal cell-derived factor-1 (CXCL12/SDF-1)
      were only affected by history of cocaine addiction. The plasma concentrations of
      interleukin 1-beta (IL-1beta), IL-6, IL-10, and tumor necrosis factor-alpha
      (TNFalpha) were affected by history of cocaine addiction and sex. In fact,
      whereas cytokine concentrations were higher in control women relative to men,
      these concentrations were reduced in cocaine-addicted women without changes in
      addicted men. Regarding fatty acid derivatives, history of cocaine addiction had
      a main effect on the concentration of each acyl derivative, whereas N-acyl
      ethanolamines were increased overall in the cocaine group, 2-acyl-glycerols were
      decreased. Interestingly, N-palmitoleoyl-ethanolamine (POEA) was only increased
      in cocaine-addicted women. The covariate BMI had a significant effect on POEA and
      N-arachidonoyl-ethanolamine concentrations. Regarding psychiatric comorbidity in
      the cocaine group, women had lower incidence rates of comorbid substance use
      disorders than did men. For example, alcohol use disorders were found in 80% of
      men and 40% of women. In contrast, the addicted women had increased prevalences
      of comorbid psychiatric disorders (i.e., mood, anxiety, and psychosis disorders).
      Additionally, cocaine-addicted subjects showed a relationship between the
      concentrations of N-stearoyl-ethanolamine and 2-linoleoyl-glycerol and diagnosis
      of psychiatric comorbidity. These results demonstrate the existence of a sex
      influence on plasma biomarkers for cocaine addiction and on the presence of
      comorbid psychopathologies for clinical purposes. 

PMID- 25762941
TI  - Support vector machine classification of major depressive disorder using
      diffusion-weighted neuroimaging and graph theory.
AB  - Recently, there has been considerable interest in understanding brain networks in
      major depressive disorder (MDD). Neural pathways can be tracked in the living
      brain using diffusion-weighted imaging (DWI); graph theory can then be used to
      study properties of the resulting fiber networks. To date, global abnormalities
      have not been reported in tractography-based graph metrics in MDD, so we used a
      machine learning approach based on "support vector machines" to differentiate
      depressed from healthy individuals based on multiple brain network properties. We
      also assessed how important specific graph metrics were for this differentiation.
      Finally, we conducted a local graph analysis to identify abnormal connectivity at
      specific nodes of the network. We were able to classify depression using whole
      brain graph metrics. Small-worldness was the most useful graph metric for
      classification. The right pars orbitalis, right inferior parietal cortex, and
      left rostral anterior cingulate all showed abnormal network connectivity in MDD.
      This is the first use of structural global graph metrics to classify depressed
      individuals. These findings highlight the importance of future research to
      understand network properties in depression across imaging modalities, improve
      classification results, and relate network alterations to psychiatric symptoms,
      medication, and comorbidities. 

PMID- 25762942
TI  - Motor imagery in clinical disorders: importance and implications.

PMID- 25762943
TI  - Importance of sex differences in impulse control and addictions.

PMID- 25762938
TI  - Schizophrenia and Depression Co-Morbidity: What We have Learned from Animal
      Models.
AB  - Patients with schizophrenia are at an increased risk for the development of
      depression. Overlap in the symptoms and genetic risk factors between the two
      disorders suggests a common etiological mechanism may underlie the presentation
      of comorbid depression in schizophrenia. Understanding these shared mechanisms
      will be important in informing the development of new treatments. Rodent models
      are powerful tools for understanding gene function as it relates to behavior.
      Examining rodent models relevant to both schizophrenia and depression reveals a
      number of common mechanisms. Current models which demonstrate endophenotypes of
      both schizophrenia and depression are reviewed here, including models of CUB and
      SUSHI multiple domains 1, PDZ and LIM domain 5, glutamate Delta 1 receptor,
      diabetic db/db mice, neuropeptide Y, disrupted in schizophrenia 1, and its
      interacting partners, reelin, maternal immune activation, and social isolation.
      Neurotransmission, brain connectivity, the immune system, the environment, and
      metabolism emerge as potential common mechanisms linking these models and
      potentially explaining comorbid depression in schizophrenia. 

PMID- 25762945
TI  - Preschoolers prefer to learn causal information.
AB  - Young children, in general, appear to have a strong drive to explore the
      environment in ways that reveal its underlying causal structure. But are they
      really attuned specifically to casual information in this quest for
      understanding, or do they show equal interest in other types of non-obvious
      information about the world? To answer this question, we introduced 20 three-year
      old children to two puppets who were anxious to tell the child about a set of
      novel artifacts and animals. One puppet consistently described causal properties
      of the items while the other puppet consistently described carefully matched non
      causal properties of the same items. After a familiarization period in which
      children learned which type of information to expect from each informant,
      children were given the opportunity to choose which they wanted to hear describe
      each of eight pictured test items. On average, children chose to hear from the
      informant that provided causal descriptions on 72% of the trials. This preference
      for causal information has important implications for explaining the role of
      conceptual information in supporting early learning and may suggest means for
      maximizing interest and motivation in young children. 

PMID- 25762944
TI  - Basics for sensorimotor information processing: some implications for learning.
AB  - In sensorimotor activities, learning requires efficient information processing,
      whether in car driving, sport activities or human-machine interactions. Several
      factors may affect the efficiency of such processing: they may be extrinsic
      (i.e., task-related) or intrinsic (i.e., subjects-related). The effects of these
      factors are intimately related to the structure of human information processing.
      In the present article we will focus on some of them, which are poorly taken into
      account, even when minimizing errors or their consequences is an essential issue
      at stake. Among the extrinsic factors, we will discuss, first, the effects of the
      quantity and quality of information, secondly, the effects of instruction and
      thirdly motor program learning. Among the intrinsic factors, we will discuss
      first the influence of prior information, secondly how individual strategies
      affect performance and, thirdly, we will stress the fact that although the human
      brain is not structured to function errorless (which is not new) humans are able
      to detect their errors very quickly and (in most of the cases), fast enough to
      correct them before they result in an overt failure. Extrinsic and intrinsic
      factors are important to take into account for learning because (1) they strongly
      affect performance, either in terms of speed or accuracy, which facilitates or
      impairs learning, (2) the effect of certain extrinsic factors may be strongly
      modified by learning and (3) certain intrinsic factors might be exploited for
      learning strategies. 

PMID- 25762946
TI  - Allocentric spatial learning and memory deficits in Down syndrome.
AB  - Studies have shown that persons with Down syndrome (DS) exhibit relatively poor
      language capacities, and impaired verbal and visuoperceptual memory, whereas
      their visuospatial memory capacities appear comparatively spared. Individuals
      with DS recall better where an object was previously seen than what object was
      previously seen. However, most of the evidence concerning preserved visuospatial
      memory comes from tabletop or computerized experiments which are biased toward
      testing egocentric (viewpoint-dependent) spatial representations. Accordingly,
      allocentric (viewpoint-independent) spatial learning and memory capacities may
      not be necessary to perform these tasks. Thus, in order to more fully
      characterize the spatial capacities of individuals with DS, allocentric processes
      underlying real-world navigation must also be investigated. We tested 20
      participants with DS and 16 mental age-matched, typically developing (TD)
      children in a real-world, allocentric spatial (AS) memory task. During local cue
      (LC) trials, participants had to locate three rewards marked by local color cues,
      among 12 locations distributed in a 4 m * 4 m arena. During AS trials,
      participants had to locate the same three rewards, in absence of LCs, based on
      their relations to distal environmental cues. All TD participants chose rewarded
      locations in LC and AS trials at above chance level. In contrast, although all
      but one of the participants with DS exhibited a preference for the rewarded
      locations in LC trials, only 50% of participants with DS chose the rewarded
      locations at above chance level in AS trials. As a group, participants with DS
      performed worse than TD children on all measures of task performance. These
      findings demonstrate that individuals with DS are impaired at using an AS
      representation to learn and remember discrete locations in a controlled
      environment, suggesting persistent and pervasive deficits in hippocampus
      dependent memory in DS. 

PMID- 25762947
TI  - Serial order learning of subliminal visual stimuli: evidence of multistage
      learning.
AB  - It is widely known that statistical learning of visual symbol sequences occurs
      implicitly (Kim et al., 2009). In this study, we examined whether people can
      learn the serial order of visual symbols when they cannot detect them. During the
      familiarization phase, triplets or quadruplets of novel symbols were presented to
      one eye under continuous flash suppression (CFS). Perception of the symbols was
      completely suppressed by the flash patterns presented to the other eye [binocular
      rivalry (BR)]. During the test phase, the detection latency was faster for
      symbols located later in the triplets or quadruplets. These results indicate that
      serial order learning occurs even when the participants cannot detect the
      stimuli. We also found that detection became slower for the last item of the
      triplets or quadruplets. This phenomenon occurred only when the participants were
      familiarized with the symbols under CFS, suggesting that the subsequent symbols
      interfered with the processing of the target symbol when conscious perception was
      suppressed. We further examined the nature of the interference and found that it
      occurred only when the subsequent symbol was not fixed. This result suggests that
      serial order learning under BR is restricted to fixed order sequences.
      Statistical learning of the symbols' transition probability might not occur when
      the participants cannot detect the symbols. We confirmed this hypothesis by
      conducting another experiment wherein the transition probability of the symbol
      sequence was manipulated. 

PMID- 25762948
TI  - Language by mouth and by hand.

PMID- 25762939
TI  - Stress-induced visceral pain: toward animal models of irritable-bowel syndrome
      and associated comorbidities.
AB  - Visceral pain is a global term used to describe pain originating from the
      internal organs, which is distinct from somatic pain. It is a hallmark of
      functional gastrointestinal disorders such as irritable-bowel syndrome (IBS).
      Currently, the treatment strategies targeting visceral pain are unsatisfactory,
      with development of novel therapeutics hindered by a lack of detailed knowledge
      of the underlying mechanisms. Stress has long been implicated in the
      pathophysiology of visceral pain in both preclinical and clinical studies. Here,
      we discuss the complex etiology of visceral pain reviewing our current
      understanding in the context of the role of stress, gender, gut microbiota
      alterations, and immune functioning. Furthermore, we review the role of
      glutamate, GABA, and epigenetic mechanisms as possible therapeutic strategies for
      the treatment of visceral pain for which there is an unmet medical need.
      Moreover, we discuss the most widely described rodent models used to model
      visceral pain in the preclinical setting. The theory behind, and application of,
      animal models is key for both the understanding of underlying mechanisms and
      design of future therapeutic interventions. Taken together, it is apparent that
      stress-induced visceral pain and its psychiatric comorbidities, as typified by
      IBS, has a multifaceted etiology. Moreover, treatment strategies still lag far
      behind when compared to other pain modalities. The development of novel,
      effective, and specific therapeutics for the treatment of visceral pain has never
      been more pertinent. 

PMID- 25762949
TI  - Evidence for similar early but not late representation of possible and impossible
      objects.
AB  - The perceptual processes that mediate the ability to efficiently represent object
      3D structure are still not fully understood. The current study was aimed to shed
      light on these processes by utilizing spatially possible and impossible objects
      that could not be created in real 3D space. Despite being perceived as
      exceptionally unusual, impossible objects still possess fundamental Gestalt
      attributes and valid local depth cues that may support their initial successful
      representation. Based on this notion and on recent findings from our lab, we
      hypothesized that the initial representation of impossible objects would involve
      common mechanisms to those mediating typical object perception while the
      perceived differences between possible and impossible objects would emerge later
      along the processing hierarchy. In Experiment 1, participants preformed
      same/different classifications of two markers superimposed on a display
      containing two objects (possible or impossible). Faster reaction times were
      observed for displays in which the markers were superimposed on the same object
      ("object-based benefit"). Importantly, this benefit was similar for possible and
      impossible objects, suggesting that the representations of the two object
      categories rely on similar perceptual organization processes. Yet, responses for
      impossible objects were slower compared to possible objects. Experiment 2 was
      designed to examine the origin of this effect. Participants classified the
      location of two markers while exposure duration was manipulated. A similar
      pattern of performance was found for possible and impossible objects for the
      short exposure duration, with differences in accuracy between these two types of
      objects emerging only for longer exposure durations. Overall, these findings
      provide evidence that the representation of object structure relies on a multi
      level process and that object impossibility selectively impairs the rendering of
      fine-detailed description of object structure. 

PMID- 25762950
TI  - The protective and detrimental effects of self-construal on perceived rejection
      from heritage culture members.
AB  - Individuals may perceive themselves as interdependent and similar with close
      others, or as independent and distinct. Do these differences in self-construal
      influence perceptions of rejection from those closest to us? Few studies have
      investigated the antecedents of intragroup marginalization - the perception of
      rejection from family and friends due to not conforming to the prescribed values
      and expectations of one's heritage culture. Furthermore, the implications of
      perceived intragroup marginalization for psychological adjustment and an
      integrated bicultural identity are unclear. To gage the effects of self
      construals on perceived intragroup marginalization and psychological adjustment
      (i.e., subjective well-being and flourishing) and an integrated bicultural
      identity, we increased the cognitive accessibility of independent and
      interdependent self-construals through a priming manipulation. Participants were
      recruited via Amazon MTurk and completed the measures online. Our results showed
      that priming an interdependent self-construal decreased perceived intragroup
      marginalization from family and, in turn, poor psychological adjustment and
      bicultural identity conflict. Conversely, participants primed with an independent
      self-construal reported increased perceptions of intragroup marginalization from
      their family and, in turn, decreased psychological adjustment and increased
      identity conflict. These findings support the benefits of an interdependent self
      and the disadvantages of an independent self for minimizing perceived exclusion
      from heritage culture members. 

PMID- 25762951
TI  - Internally and externally generated emotions in people with acquired brain
      injury: preservation of emotional experience after right hemisphere lesions.
AB  - The study of emotional changes after brain injury has contributed enormously to
      the understanding of the neural basis of emotion. However, little attention has
      been placed on the methods used to elicit emotional responses in people with
      brain damage. Of particular interest are subjects with right hemisphere [RH]
      cortical lesions, who have been described as presenting impairment in emotional
      processing. In this article, an internal and external mood induction procedure
      [MIP] was used to trigger positive and negative emotions, in a sample of 10
      participants with RH damage, and 15 healthy controls. Emotional experience was
      registered by using a self-report questionnaire. As observed in previous studies,
      internal and external MIPs were equally effective in eliciting the target
      emotion, but the internal procedure generated higher levels of intensity.
      Remarkably, participants with RH lesions were equally able to experience both
      positive and negative affect. The results are discussed in relation to the role
      of the RH in the capacity to experience negative emotions. 

PMID- 25762952
TI  - The prosocial personality and its facets: genetic and environmental architecture
      of mother-reported behavior of 7-year-old twins.
AB  - Children vary markedly in their tendency to behave prosocially, and recent
      research has implicated both genetic and environmental factors in this
      variability. Yet, little is known about the extent to which different aspects of
      prosociality constitute a single dimension (the prosocial personality), and to
      the extent they are intercorrelated, whether these aspects share their genetic
      and environmental origins. As part of the Longitudinal Israeli Study of Twins
      (LIST), mothers of 183 monozygotic (MZ) and dizygotic (DZ) 7-year-old twin pairs
      (51.6% male) reported regarding their children's prosociality using
      questionnaires. Five prosociality facets (sharing, social concern, kindness,
      helping, and empathic concern) were identified. All five facets intercorrelated
      positively (r > 0.39) suggesting a single-factor structure to the data,
      consistent with the theoretical idea of a single prosociality trait. Higher MZ
      than DZ twin correlations indicated genetic contributions to each prosociality
      facet. A common-factor-common-pathway multivariate model estimated high (69%)
      heritability for the common prosociality factor, with the non-shared environment
      and error accounting for the remaining variance. For each facet, unique genetic
      and environmental contributions were identified as well. The results point to the
      presence of a broad prosociality phenotype, largely affected by genetics; whereas
      additional genetic and environmental factors contribute to different aspects of
      prosociality, such as helping and sharing. 

PMID- 25762953
TI  - Learned fear to social out-group members are determined by ethnicity and prior
      exposure.
AB  - Humans, like other animals, have a tendency to preferentially learn and retain
      some associations more readily than others. In humans, preferential learning was
      originally demonstrated for certain evolutionary prepared stimuli, such as snakes
      and angry faces and later extended to human social out-groups based on race
      (Olsson et al., 2005). To address the generality of this social learning bias, we
      examined if this learning bias extended to two separate classes of social out
      groups represented by neutral Black and Middle-Eastern faces in 38 White
      (Swedish) participants. We found that other-ethnicity alone was not sufficient to
      induce an out-group learning bias; it was observed for Black, but not Middle
      Eastern, out-group faces. Moreover, an exploratory analysis showed that growing
      up in an ethnically diverse environment was inversely related to the learning
      bias toward Middle-Eastern, but not Black, out-groups faces, suggesting that
      learned fears toward Middle-Eastern faces might be more permeable to
      environmental factors. Future research should address how both the quantity and
      quality of inter-group contact modulate out-group learning. 

PMID- 25762954
TI  - Bridging and bonding interactions in higher education: social capital and
      students' academic and professional identity formation.
AB  - It is increasingly recognized that graduates' achievements depend in important
      ways on their opportunities to develop an academic and a professional identity
      during their studies. Previous research has shown that students' socio-economic
      status (SES) and social capital prior to entering university affects their
      ability to obtain these identities in higher education. However, what is less
      well understood is whether social capital that is built during university studies
      shapes identity development, and if so, whether the social capital gained during
      university years impacts on academic and professional identity differently. In a
      qualitative study, we interviewed 26 Danish and 11 Australian university students
      about their social interaction experiences, their opportunities to develop
      bonding capital as well as bridging capital, and their academic and professional
      identity. Findings show that while bonding social capital with co-students
      facilitated academic identity formation, such social capital does not lead to
      professional identity development. We also found that the development of bridging
      social capital with educators facilitated students' professional identity
      formation. However, bonding social capital among students stood in the way of
      participating in bridging interaction with educators, thereby further hindering
      professional identity formation. Finally, while students' parental background did
      not affect the perceived difficulty of forming professional identity, there was a
      tendency for students from lower SES backgrounds to be more likely to make
      internal attributions while those from higher SES backgrounds were more likely to
      make external attributions for the failure to develop professional identity.
      Results point to the importance of creating opportunities for social interaction
      with educators at university because this facilitates the generation of bridging
      social capital, which, in turn, is essential for students' professional identity
      development. 

PMID- 25762955
TI  - Lexical alignment in triadic communication.
AB  - Lexical alignment refers to the adoption of one's interlocutor's lexical items.
      Accounts of the mechanisms underlying such lexical alignment differ (among other
      aspects) in the role assigned to addressee-centered behavior. In this study, we
      used a triadic communicative situation to test which factors may modulate the
      extent to which participants' lexical alignment reflects addressee-centered
      behavior. Pairs of naive participants played a picture matching game and received
      information about the order in which pictures were to be matched from a voice
      over headphones. On critical trials, participants did or did not hear a name for
      the picture to be matched next over headphones. Importantly, when the voice over
      headphones provided a name, it did not match the name that the interlocutor had
      previously used to describe the object. Participants overwhelmingly used the word
      that the voice over headphones provided. This result points to non-addressee
      centered behavior and is discussed in terms of disrupting alignment with the
      interlocutor as well as in terms of establishing alignment with the voice over
      headphones. In addition, the type of picture (line drawing vs. tangram shape)
      independently modulated lexical alignment, such that participants showed more
      lexical alignment to their interlocutor for (more ambiguous) tangram shapes
      compared to line drawings. Overall, the results point to a rather large role for
      non-addressee-centered behavior during lexical alignment. 

PMID- 25762956
TI  - Corrugator activity confirms immediate negative affect in surprise.
AB  - The emotion of surprise entails a complex of immediate responses, such as
      cognitive interruption, attention allocation to, and more systematic processing
      of the surprising stimulus. All these processes serve the ultimate function to
      increase processing depth and thus cognitively master the surprising stimulus.
      The present account introduces phasic negative affect as the underlying mechanism
      responsible for this switch in operating mode. Surprising stimuli are schema
      discrepant and thus entail cognitive disfluency, which elicits immediate negative
      affect. This affect in turn works like a phasic cognitive tuning switching the
      current processing mode from more automatic and heuristic to more systematic and
      reflective processing. Directly testing the initial elicitation of negative
      affect by surprising events, the present experiment presented high and low
      surprising neutral trivia statements to N = 28 participants while assessing their
      spontaneous facial expressions via facial electromyography. High compared to low
      surprising trivia elicited higher corrugator activity, indicative of negative
      affect and mental effort, while leaving zygomaticus (positive affect) and
      frontalis (cultural surprise expression) activity unaffected. Future research
      shall investigate the mediating role of negative affect in eliciting surprise
      related outcomes. 

PMID- 25762957
TI  - Event-related potentials during word mapping to object shape predict toddlers'
      vocabulary size.
AB  - What role does attention to different object properties play in early vocabulary
      development? This longitudinal study using event-related potentials in
      combination with behavioral measures investigated 20- and 24-month-olds' (n = 38;
      n = 34; overlapping n = 24) ability to use object shape and object part
      information in word-object mapping. The N400 component was used to measure
      semantic priming by images containing shape or detail information. At 20 months,
      the N400 to words primed by object shape varied in topography and amplitude
      depending on vocabulary size, and these differences predicted productive
      vocabulary size at 24 months. At 24 months, when most of the children had
      vocabularies of several hundred words, the relation between vocabulary size and
      the N400 effect in a shape context was weaker. Detached object parts did not
      function as word primes regardless of age or vocabulary size, although the part
      objects were identified behaviorally. The behavioral measure, however, also
      showed relatively poor recognition of the part-objects compared to the shape
      objects. These three findings provide new support for the link between shape
      recognition and early vocabulary development. 

PMID- 25762959
TI  - Awareness shaping or shaped by prediction and postdiction: Editorial.

PMID- 25762958
TI  - The impact of motivation and teachers' autonomy support on children's executive
      functions.
AB  - The present study investigates the interplay of executive functions, motivation,
      and teacher's autonomy support in school context. In a cross-sectional study
      design 208 students from different school types completed a standardized
      motivation questionnaire and processed two executive function tasks. All teachers
      who teach these students were asked about their autonomy supporting behavior by a
      standardized test. Multilevel analyses assessed the effects of the student's
      motivation and their teachers' autonomy support on student's executive functions.
      Our results show considerable relationships between these variables: high
      executive function capacities came along with teacher's autonomy support and
      student's intrinsic motivation styles, whereas low executive function capacities
      were related to external regulation styles. The results indicate the importance
      of autonomy support in school instruction and disclose the need to popularize the
      self-regulation approach. 

PMID- 25762960
TI  - Two perils of binary categorization: why the study of concepts can't afford
      true/false testing.

PMID- 25762961
TI  - The role of school performance in narrowing gender gaps in the formation of STEM
      aspirations: a cross-national study.
AB  - This study uses cross-national evidence to estimate the effect of school peer
      performance on the size of the gender gap in the formation of STEM career
      aspirations. We argue that STEM aspirations are influenced not only by gender
      stereotyping in the national culture but also by the performance of peers in the
      local school environment. Our analyses are based on the Program for International
      Student Assessment (PISA). They investigate whether 15-year-old students from 55
      different countries expect to have STEM jobs at the age of 30. We find
      considerable gender differences in the plans to pursue careers in STEM
      occupations in all countries. Using PISA test scores in math and science
      aggregated at the school level as a measure of school performance, we find that
      stronger performance environments have a negative impact on student career
      aspirations in STEM. Although girls are less likely than boys to aspire to STEM
      occupations, even when they have comparable abilities, boys respond more than
      girls to competitive school performance environments. As a consequence, the
      aspirations gender gap narrows for high-performing students in stronger
      performance environments. We show that those effects are larger in countries that
      do not sort students into different educational tracks. 

PMID- 25762962
TI  - Is conflict adaptation an illusion?

PMID- 25762963
TI  - The association between mood and anxiety disorders, and coronary heart disease in
      Brazil: a cross-sectional analysis on the Brazilian longitudinal study of adult
      health (ELSA-Brasil).
AB  - BACKGROUND: Associations between major depressive disorder (MDD) and coronary
      heart disease (CHD) have been established, and these associations increase risk
      of future morbidity and mortality. Prior research has been carried out in high
      income countries. Here we examine associations between the mood and anxiety
      disorders, and CHD in a large cohort at baseline from Brazil, a country facing a
      variety of challenges that may affect these associations. METHODS: Participants
      included 15,105 civil servants aged 35 to 74 at baseline (2008-2010) from the
      Brazilian Longitudinal Study of Adult Health (ELSA-Brasil). CHD (N = 721)
      included self-reported angina pectoris (n = 305), myocardial infarction (n = 259)
      and coronary revascularization (n = 239). Hierarchical logistic regression
      analyses were conducted to estimate odds ratios and confidence intervals.
      RESULTS: Major findings indicate that comorbid MDD and anxiety disorders (n =
      434) are associated with a threefold increase in CHD, MDD alone (n = 170) with a
      twofold increase in CHD, while generalized anxiety disorder alone (n = 1,394) and
      mixed anxiety and depression disorder (n = 1,844) - symptoms present, but
      diagnostic threshold not reached - are associated with a 1.5-fold increase in
      CHD, after full adjustment for covariates. CONCLUSION: The association with CHD
      is greatest in those with psychiatric comorbidity, while associations were also
      observed in MDD and generalized anxiety disorder without comorbidity. While
      findings are limited by the cross-sectional design of the study, given the known
      risks associated with comorbidity of the mood and anxiety disorders with CHD,
      findings reinforce the importance of comprehensive health assessment in Brazil.

PMID- 25762964
TI  - All STEM fields are not created equal: People and things interests explain gender
      disparities across STEM fields.
AB  - The degree of women's underrepresentation varies by STEM fields. Women are now
      overrepresented in social sciences, yet only constitute a fraction of the
      engineering workforce. In the current study, we investigated the gender
      differences in interests as an explanation for the differential distribution of
      women across sub-disciplines of STEM as well as the overall underrepresentation
      of women in STEM fields. Specifically, we meta-analytically reviewed norm data on
      basic interests from 52 samples in 33 interest inventories published between 1964
      and 2007, with a total of 209,810 male and 223,268 female respondents. We found
      gender differences in interests to vary largely by STEM field, with the largest
      gender differences in interests favoring men observed in engineering disciplines
      (d = 0.83-1.21), and in contrast, gender differences in interests favoring women
      in social sciences and medical services (d = -0.33 and -0.40, respectively).
      Importantly, the gender composition (percentages of women) in STEM fields
      reflects these gender differences in interests. The patterns of gender
      differences in interests and the actual gender composition in STEM fields were
      explained by the people-orientation and things-orientation of work environments,
      and were not associated with the level of quantitative ability required. These
      findings suggest potential interventions targeting interests in STEM education to
      facilitate individuals' ability and career development and strategies to reform
      work environments to better attract and retain women in STEM occupations. 

PMID- 25762965
TI  - Bayesian reasoning with ifs and ands and ors.
AB  - The Bayesian approach to the psychology of reasoning generalizes binary logic,
      extending the binary concept of consistency to that of coherence, and allowing
      the study of deductive reasoning from uncertain premises. Studies in judgment and
      decision making have found that people's probability judgments can fail to be
      coherent. We investigated people's coherence further for judgments about
      conjunctions, disjunctions and conditionals, and asked whether their coherence
      would increase when they were given the explicit task of drawing inferences.
      Participants gave confidence judgments about a list of separate statements (the
      statements group) or the statements grouped as explicit inferences (the
      inferences group). Their responses were generally coherent at above chance levels
      for all the inferences investigated, regardless of the presence of an explicit
      inference task. An exception was that they were incoherent in the context known
      to cause the conjunction fallacy, and remained so even when they were given an
      explicit inference. The participants were coherent under the assumption that they
      interpreted the natural language conditional as it is represented in Bayesian
      accounts of conditional reasoning, but they were incoherent under the assumption
      that they interpreted the natural language conditional as the material
      conditional of elementary binary logic. Our results provide further support for
      the descriptive adequacy of Bayesian reasoning principles in the study of
      deduction under uncertainty. 

PMID- 25762966
TI  - The development of socio-motivational dependency from early to middle
      adolescence.
AB  - Research on students' motivation has shown that motivation can be enhanced or
      undermined by social factors. However, when interpreting such findings,
      interindividual differences, and intraindividual changes underlying students'
      perception of peers and teachers as a source of motivation are often neglected.
      The aim of the present study was to complement our understanding of socio
      motivational dependency by investigating differences in the development of
      students' socio-motivational dependency from early to middle adolescence. Data
      from 1088 students on their perceptions of peers and teachers as positive
      motivators when students were in seventh and eighth grade were compared with data
      of the same sample 2 years later. Latent class analysis supported four different
      motivation types (MT): (1) teacher-dependent MT, (2) peer-dependent MT, (3)
      teacher-and-peer-dependent MT, and (4) teacher-and-peer-independent MT. Latent
      transition analysis revealed substantial changes between the groups. The
      perceived teacher influence on students' academic motivation increased from early
      to middle adolescence. Divergent roles of peers and teachers on students'
      academic motivation are discussed. 

PMID- 25762967
TI  - Walking in the uncanny valley: importance of the attractiveness on the acceptance
      of a robot as a working partner.
AB  - The Uncanny valley hypothesis, which tells us that almost-human characteristics
      in a robot or a device could cause uneasiness in human observers, is an important
      research theme in the Human Robot Interaction (HRI) field. Yet, that phenomenon
      is still not well-understood. Many have investigated the external design of
      humanoid robot faces and bodies but only a few studies have focused on the
      influence of robot movements on our perception and feelings of the Uncanny
      valley. Moreover, no research has investigated the possible relation between our
      uneasiness feeling and whether or not we would accept robots having a job in an
      office, a hospital or elsewhere. To better understand the Uncanny valley, we
      explore several factors which might have an influence on our perception of
      robots, be it related to the subjects, such as culture or attitude toward robots,
      or related to the robot such as emotions and emotional intensity displayed in its
      motion. We asked 69 subjects (N = 69) to rate the motions of a humanoid robot
      (Perceived Humanity, Eeriness, and Attractiveness) and state where they would
      rather see the robot performing a task. Our results suggest that, among the
      factors we chose to test, the attitude toward robots is the main influence on the
      perception of the robot related to the Uncanny valley. Robot occupation
      acceptability was affected only by Attractiveness, mitigating any Uncanny valley
      effect. We discuss the implications of these findings for the Uncanny valley and
      the acceptability of a robotic worker in our society. 

PMID- 25762968
TI  - Progress and current challenges with the quantum similarity model.

PMID- 25762969
TI  - Conspiracy theory and cognitive style: a worldview.
AB  - This paper assessed whether belief in conspiracy theories was associated with a
      particularly cognitive style (worldview). The sample comprised 223 volunteers
      recruited via convenience sampling and included undergraduates, postgraduates,
      university employees, and alumni. Respondents completed measures assessing a
      range of cognitive-perceptual factors (schizotypy, delusional ideation, and
      hallucination proneness) and conspiratorial beliefs (general attitudes toward
      conspiracist thinking and endorsement of individual conspiracies). Positive
      symptoms of schizotypy, particularly the cognitive-perceptual factor, correlated
      positively with conspiracist beliefs. The best predictor of belief in
      conspiracies was delusional ideation. Consistent with the notion of a coherent
      conspiratorial mindset, scores across conspiracy measures correlated strongly.
      Whilst findings supported the view that belief in conspiracies, within the sub
      clinical population, was associated with a delusional thinking style, cognitive
      perceptual factors in combination accounted for only 32% of the variance. 

PMID- 25762970
TI  - "Wesley says": a children's response inhibition playground training game yields
      preliminary evidence of transfer effects.
AB  - Recent studies suggest that the response inhibition ability of children can be
      modified through training. Based on the notion of embodied cognition, we
      investigated transfer effects of a 7-day training program using a game named
      "Wesley says" in 8- to 12-year-old children (n = 15). The game consists of
      providing commands for performing simple body actions, the actual execution of
      which is conditional upon the preceding verbal expression "Wesley says." Training
      effects were assessed with a computer-based visual go/no-go task and the Stroop
      color-word interference task. Relative to a control group playing other games
      mainly involving physical exercise (n = 15), the trained group showed a
      performance improvement on the go/no-go task, but not on the Stroop task. These
      results suggest the potential of an easy-to-use and ecologically valid training
      game to improve the inhibition capacity of children on related response
      inhibition tasks but not on tasks measuring other aspects of inhibition, such as
      interference control. 

PMID- 25762971
TI  - Autoethnography helps analyse emotions.

PMID- 25762972
TI  - Coping with levels of explanation in the behavioral sciences.

PMID- 25762973
TI  - Sequential egocentric navigation and reliance on landmarks in Williams syndrome
      and typical development.
AB  - Visuospatial difficulties in Williams syndrome (WS) are well documented.
      Recently, research has shown that spatial difficulties in WS extend to large
      scale space, particularly in coding space using an allocentric frame of
      reference. Typically developing (TD) children and adults predominantly rely on
      the use of a sequential egocentric strategy to navigate a large-scale route
      (retracing a sequence of left-right body turns). The aim of this study was to
      examine whether individuals with WS are able to employ a sequential egocentric
      strategy to guide learning and the retracing of a route. Forty-eight TD children,
      aged 5, 7, and 9 years and 18 participants with WS were examined on their ability
      to learn and retrace routes in two (6-turn) virtual environment mazes (with and
      without landmarks). The ability to successfully retrace a route following the
      removal of landmarks (use of sequential egocentric coding) was also examined.
      Although in line with TD 5-year-olds when learning a route with landmarks,
      individuals with WS showed significantly greater detriment when these landmarks
      were removed, relative to all TD groups. Moreover, the WS group made
      significantly more errors than all TD groups when learning a route that never
      contained landmarks. On a perceptual view-matching task, results revealed a high
      level of performance across groups, indicative of an ability to use this visual
      information to potentially aid navigation. These findings suggest that
      individuals with WS rely on landmarks to a greater extent than TD children, both
      for learning a route and for retracing a recently learned route. TD children, but
      not individuals with WS, were able to fall back on the use of a sequential
      egocentric strategy to navigate when landmarks were not present. Only TD children
      therefore coded sequential route information simultaneously with landmark
      information. The results are discussed in relation to known atypical cortical
      development and perceptual-matching abilities in WS. 

PMID- 25762974
TI  - Individual differences in attention influence perceptual decision making.
AB  - Sequential sampling decision-making models have been successful in accounting for
      reaction time (RT) and accuracy data in two-alternative forced choice tasks.
      These models have been used to describe the behavior of populations of
      participants, and explanatory structures have been proposed to account for
      between individual variability in model parameters. In this study we show that
      individual differences in behavior from a novel perceptual decision making task
      can be attributed to (1) differences in evidence accumulation rates, (2)
      differences in variability of evidence accumulation within trials, and (3)
      differences in non-decision times across individuals. Using
      electroencephalography (EEG), we demonstrate that these differences in cognitive
      variables, in turn, can be explained by attentional differences as measured by
      phase-locking of steady-state visual evoked potential (SSVEP) responses to the
      signal and noise components of the visual stimulus. Parameters of a cognitive
      model (a diffusion model) were obtained from accuracy and RT distributions and
      related to phase-locking indices (PLIs) of SSVEPs with a single step in a
      hierarchical Bayesian framework. Participants who were able to suppress the SSVEP
      response to visual noise in high frequency bands were able to accumulate correct
      evidence faster and had shorter non-decision times (preprocessing or motor
      response times), leading to more accurate responses and faster response times. We
      show that the combination of cognitive modeling and neural data in a hierarchical
      Bayesian framework relates physiological processes to the cognitive processes of
      participants, and that a model with a new (out-of-sample) participant's neural
      data can predict that participant's behavior more accurately than models without
      physiological data. 

PMID- 25762975
TI  - Influence of inflammatory disorders and infection on iron absorption and efficacy
      of iron-fortified foods.
AB  - The provision of iron- fortified foods is a common strategy to prevent iron
      deficiency; however, ensuring adequate iron absorption is a challenge. Iron
      bioavailability depends on the choice of iron compound, the presence enhancers
      and inhibitors of absorption in the food matrix, and the physiological state of
      the consumer, including iron status, other nutritional deficiencies and
      inflammatory disorders. Inflammation associated with infections and inflammatory
      disorders would be expected to decrease iron absorption and reduce the efficacy
      of iron- fortified foods. The decreased absorption is due to an increase in
      circulating hepcidin in response to inflammatory cytokines. Hepcidin degrades
      ferroportin and blocks the passage of iron from the intestinal cell to the
      plasma. This is the innate immune response to infections and aims to restrict
      pathogen growth by restricting iron supply. Stable isotope studies have reported
      women and children with chronic malaria parasitemia or febrile malaria to have
      increased inflammatory cytokines, increased hepcidin and much decreased iron
      absorption. No studies have specifically investigated the efficacy of iron-
      fortified foods in the absence and presence of infections. In contrast,
      inflammation and increased hepcidin associated with adiposity in overweight have
      been linked to both lower iron absorption and the decreased efficacy of iron-
      fortified foods. 

PMID- 25762976
TI  - Safety of iron fortification and supplementation in malaria-endemic areas.
AB  - This review considers the safety of iron supplementation and fortification for
      the prevention and correction of iron deficiency in malaria-endemic areas, with a
      focus on potential means whereby provision of additional iron might heighten the
      risks of malaria and other infections. Iron deficiency itself may increase the
      risk of morbidity and mortality from malaria and other infections. The available
      evidence indicates that iron interventions are safe in settings without endemic
      malaria, and, with adequate health care, in regions with high transmission of
      malaria and other infections. Without regular surveillance and treatment of
      malaria and other infections, iron supplementation of individuals who are iron
      deficient seems safe, but individuals who are iron replete may have an increased
      risk of adverse outcomes. The mechanisms responsible for harmful effects with
      iron supplementation have not been established. These are likely to include the
      effects of (a) increased amounts of absorbed iron, with the production of plasma
      non-transferrin-bound iron, (b) increased amounts of iron in the gastrointestinal
      tract, with effects on gastrointestinal structural integrity and on gut
      microflora, and (c) the complex immune effects of iron interventions. Iron
      fortification appears to be generally safe, although more data from malaria
      endemic areas are needed. 

PMID- 25762977
TI  - Multimodal imaging of dynamic functional connectivity.
AB  - The study of large-scale functional interactions in the human brain with
      functional magnetic resonance imaging (fMRI) extends almost to the first
      applications of this technology. Due to historical reasons and preconceptions
      about the limitations of this brain imaging method, most studies have focused on
      assessing connectivity over extended periods of time. It is now clear that fMRI
      can resolve the temporal dynamics of functional connectivity, like other faster
      imaging techniques such as electroencephalography and magnetoencephalography
      (albeit on a different temporal scale). However, the indirect nature of fMRI
      measurements can hinder the interpretability of the results. After briefly
      summarizing recent advances in the field, we discuss how the simultaneous
      combination of fMRI with electrophysiological activity measurements can
      contribute to a better understanding of dynamic functional connectivity in humans
      both during rest and task, wakefulness, and other brain states. 

PMID- 25762978
TI  - EEG Spectral Features Discriminate between Alzheimer's and Vascular Dementia.
AB  - Alzheimer's disease (AD) and vascular dementia (VaD) present with similar
      clinical symptoms of cognitive decline, but the underlying pathophysiological
      mechanisms differ. To determine whether clinical electroencephalography (EEG) can
      provide information relevant to discriminate between these diagnoses, we used
      quantitative EEG analysis to compare the spectra between non-medicated patients
      with AD (n = 77) and VaD (n = 77) and healthy elderly normal controls (NC) (n =
      77). We use curve-fitting with a combination of a power loss and Gaussian
      function to model the averaged resting-state spectra of each EEG channel
      extracting six parameters. We assessed the performance of our model and tested
      the extracted parameters for group differentiation. We performed regression
      analysis in a multivariate analysis of covariance with group, age, gender, and
      number of epochs as predictors and further explored the topographical group
      differences with pair-wise contrasts. Significant topographical differences
      between the groups were found in several of the extracted features. Both AD and
      VaD groups showed increased delta power when compared to NC, whereas the AD
      patients showed a decrease in alpha power for occipital and temporal regions when
      compared with NC. The VaD patients had higher alpha power than NC and AD. The AD
      and VaD groups showed slowing of the alpha rhythm. Variability of the alpha
      frequency was wider for both AD and VaD groups. There was a general decrease in
      beta power for both AD and VaD. The proposed model is useful to parameterize
      spectra, which allowed extracting relevant clinical EEG key features that move
      toward simple and interpretable diagnostic criteria. 

PMID- 25762979
TI  - The Ellipsoid Factor for Quantification of Rods, Plates, and Intermediate Forms
      in 3D Geometries.
AB  - The ellipsoid factor (EF) is a method for the local determination of the rod- or
      plate-like nature of porous or spongy continua. EF at a point within a 3D
      structure is defined as the difference in axis ratios of the greatest ellipsoid
      that fits inside the structure and that contains the point of interest, and
      ranges from -1 for strongly oblate (discus-shaped) ellipsoids, to +1 for strongly
      prolate (javelin-shaped) ellipsoids. For an ellipsoid with axes a <= b <= c, EF =
      a/b - b/c. Here, EF is demonstrated in a Java plugin, "Ellipsoid Factor" for
      ImageJ, distributed in the BoneJ plugin collection. Ellipsoid Factor utilizes an
      ellipsoid optimization algorithm, which assumes that maximal ellipsoids are
      centered on the medial axis, then dilates, rotates, and translates slightly each
      ellipsoid until it cannot increase in volume any further. EF successfully
      identifies rods, plates, and intermediate structures within trabecular bone, and
      summarizes the distribution of geometries with an overall EF mean and SD, EF
      histogram, and Flinn diagram displaying a/b versus b/c. EF is released to the
      community for testing, use, and improvement. 

PMID- 25762981
TI  - Partial-Hepatectomized (70%) Model Shows a Correlation between Hepatocyte Growth
      Factor Levels and Beta-Cell Mass.

PMID- 25762982
TI  - Oligotyping reveals stronger relationship of organic soil bacterial community
      structure with N-amendments and soil chemistry in comparison to that of mineral
      soil at Harvard Forest, MA, USA.
AB  - The impact of chronic nitrogen amendments on bacterial communities was evaluated
      at Harvard Forest, Petersham, MA, USA. Thirty soil samples (3 treatments * 2 soil
      horizons * 5 subplots) were collected in 2009 from untreated (control), low
      nitrogen-amended (LN; 50 kg NH4NO3 ha(-1) yr(-1)) and high nitrogen-amended (HN;
      150 kg NH4NO3 ha(-1) yr(-1)) plots. PCR-amplified partial 16S rRNA gene sequences
      made from soil DNA were subjected to pyrosequencing (Turlapati et al., 2013) and
      analyses using oligotyping. The parameters M (the minimum count of the most
      abundant unique sequence in an oligotype) and s (the minimum number of samples in
      which an oligotype is expected to be present) had to be optimized for forest
      soils because of high diversity and the presence of rare organisms. Comparative
      analyses of the pyrosequencing data by oligotyping and operational taxonomic unit
      clustering tools indicated that the former yields more refined units of taxonomy
      with sequence similarity of >=99.5%. Sequences affiliated with four new phyla and
      73 genera were identified in the present study as compared to 27 genera reported
      earlier from the same data (Turlapati et al., 2013). Significant rearrangements
      in the bacterial community structure were observed with N-amendments revealing
      the presence of additional genera in N-amended plots with the absence of some
      that were present in the control plots. Permutational MANOVA analyses indicated
      significant variation associated with soil horizon and N treatment for a majority
      of the phyla. In most cases soil horizon partitioned more variation relative to
      treatment and treatment effects were more evident for the organic (Org) horizon.
      Mantel test results for Org soil showed significant positive correlations between
      bacterial communities and most soil parameters including NH4 and NO3. In mineral
      soil, correlations were seen only with pH, NH4, and NO3. Regardless of the
      pipeline used, a major hindrance for such a study remains to be the lack of
      reference databases for forest soils. 

PMID- 25762980
TI  - Membrane-initiated non-genomic signaling by estrogens in the hypothalamus: cross
      talk with glucocorticoids with implications for behavior.
AB  - The estrogen receptor and glucocorticoid receptor are members of the nuclear
      receptor superfamily that can signal using both non-genomic and genomic
      transcriptional modes. Though genomic modes of signaling have been well
      characterized and several behaviors attributed to this signaling mechanism, the
      physiological significance of non-genomic modes of signaling has not been well
      understood. This has partly been due to the controversy regarding the identity of
      the membrane ER (mER) or membrane GR (mGR) that may mediate rapid, non-genomic
      signaling and the downstream signaling cascades that may result as a consequence
      of steroid ligands binding the mER or the mGR. Both estrogens and glucocorticoids
      exert a number of actions on the hypothalamus, including feedback. This review
      focuses on the various candidates for the mER or mGR in the hypothalamus and the
      contribution of non-genomic signaling to classical hypothalamically driven
      behaviors and changes in neuronal morphology. It also attempts to categorize some
      of the possible functions of non-genomic signaling at both the cellular level and
      at the organismal level that are relevant for behavior, including some behaviors
      that are regulated by both estrogens and glucocorticoids in a potentially
      synergistic manner. Lastly, it attempts to show that steroid signaling via non
      genomic modes may provide the organism with rapid behavioral responses to
      stimuli. 

PMID- 25762983
TI  - Host response during Yersinia pestis infection of human bronchial epithelial
      cells involves negative regulation of autophagy and suggests a modulation of
      survival-related and cellular growth pathways.
AB  - Yersinia pestis (Yp) causes the re-emerging disease plague, and is classified by
      the CDC and NIAID as a highest priority (Category A) pathogen. Currently, there
      is no approved human vaccine available and advances in early diagnostics and
      effective therapeutics are urgently needed. A deep understanding of the
      mechanisms of host response to Yp infection can significantly advance these three
      areas. We employed the Reverse Phase Protein Microarray (RPMA) technology to
      reveal the dynamic states of either protein level changes or phosphorylation
      changes associated with kinase-driven signaling pathways during host cell
      response to Yp infection. RPMA allowed quantitative profiling of changes in the
      intracellular communication network of human lung epithelial cells at different
      times post infection and in response to different treatment conditions, which
      included infection with the virulent Yp strain CO92, infection with a derivative
      avirulent strain CO92 (Pgm-, Pst-), treatment with heat inactivated CO92, and
      treatment with LPS. Responses to a total of 111 validated antibodies were
      profiled, leading to discovery of 12 novel protein hits. The RPMA analysis also
      identified several protein hits previously reported in the context of Yp
      infection. Furthermore, the results validated several proteins previously
      reported in the context of infection with other Yersinia species or implicated
      for potential relevance through recombinant protein and cell transfection
      studies. The RPMA results point to strong modulation of survival/apoptosis and
      cell growth pathways during early host response and also suggest a model of
      negative regulation of the autophagy pathway. We find significant cytoplasmic
      localization of p53 and reduced LC3-I to LC3-II conversion in response to Yp
      infection, consistent with negative regulation of autophagy. These studies allow
      for a deeper understanding of the pathogenesis mechanisms and the discovery of
      innovative approaches for prevention, early diagnosis, and treatment of plague. 

PMID- 25762984
TI  - Helicobacter pylori infection reduces disease severity in an experimental model
      of multiple sclerosis.
AB  - Recent research has demonstrated that infection with the bacterial pathogen
      Helicobacter pylori is less common amongst patients with multiple sclerosis (MS),
      an inflammatory demyelinating disease of the central nervous system (CNS). We
      aimed to compare the prevalence of H. pylori amongst MS patients and healthy
      controls, and also investigated the impact of this infection on an animal model
      for MS, experimental autoimmune encephalomyelitis (EAE). The H. pylori status of
      71 MS patients and 42 healthy controls was determined by serology. Groups of
      C57BL/6 mice were infected with H. pylori, or given diluent alone as a placebo,
      prior to inducing EAE. Clinical scores were assessed for all mice, and spleens
      and spinal cord tissue were harvested. CD4(+) T cell subsets were quantified by
      flow cytometry, and T cell proliferation assays were performed. In MS patients
      the seroprevalence of H. pylori was half that of healthy controls (p = 0.018).
      Over three independent experiments, prior H. pylori infection had a moderate
      effect in reducing the severity of EAE (p = 0.012). In line with this, the
      antigen-specific T cell proliferative responses of infected animals were
      significantly reduced (p = 0.001), and there was a fourfold reduction in the
      number of CD4(+) cells in the CNS. CD4(+) populations in both the CNS and the
      spleens of infected mice also contained greatly reduced proportions of
      IFNgamma(+), IL-17(+), T-bet(+), and RORgammat(+) cells, but the proportions of
      Foxp3(+) cells were equivalent. There were no differences in the frequency of
      splenic CD4(+)cells expressing markers of apoptosis between infected and
      uninfected animals. H. pylori was less prevalent amongst MS patients. In mice,
      the infection exerted some protection against EAE, inhibiting both Th1 and Th17
      responses. This could not be explained by the presence of increased numbers of
      Foxp3(+) regulatory T cells, or T cell apoptosis. This is the first direct
      experimental evidence showing that H. pylori may provide protection against
      inflammatory demyelination in the CNS. 

PMID- 25762986
TI  - Rhamnolipids: solution against Aedes aegypti?
AB  - Aedes aegypti mosquitoes are the primary transmitters of dengue fever, urban
      yellow fever, and chikungunya viruses. This mosquito has developed resistance to
      the insecticides currently used to control their populations. These chemical
      insecticides are harmful to the environment and can have negative effects on
      human health. Rhamnolipids are environmentally compatible biological surfactants,
      but their insecticidal activity has not been extensively studied. The present
      study evaluated the potential larvicidal, insecticidal, and repellent activities
      of rhamnolipids against A. aegypti. At concentrations of 800, 900, and 1000 mg/L,
      rhamnolipids eliminated all mosquito larvae in 18 h and killed 100% of adults at
      1000 mg/L. According to the results it may be conclude that rhamnolipids should
      be applied to control larvae and mosquitos besides present the repellency
      activity against A. aegypti. 

PMID- 25762985
TI  - Association of fungal secondary metabolism and sclerotial biology.
AB  - Fungal secondary metabolism and morphological development have been shown to be
      intimately associated at the genetic level. Much of the literature has focused on
      the co-regulation of secondary metabolite production (e.g., sterigmatocystin and
      aflatoxin in Aspergillus nidulans and Aspergillus flavus, respectively) with
      conidiation or formation of sexual fruiting bodies. However, many of these
      genetic links also control sclerotial production. Sclerotia are resistant
      structures produced by a number of fungal genera. They also represent the
      principal source of primary inoculum for some phytopathogenic fungi. In nature,
      higher plants often concentrate secondary metabolites in reproductive structures
      as a means of defense against herbivores and insects. By analogy, fungi also
      sequester a number of secondary metabolites in sclerotia that act as a chemical
      defense system against fungivorous predators. These include antiinsectant
      compounds such as tetramic acids, indole diterpenoids, pyridones, and
      diketopiperazines. This chapter will focus on the molecular mechanisms governing
      production of secondary metabolites and the role they play in sclerotial
      development and fungal ecology, with particular emphasis on Aspergillus species.
      The global regulatory proteins VeA and LaeA, components of the velvet nuclear
      protein complex, serve as virulence factors and control both development and
      secondary metabolite production in many Aspergillus species. We will discuss a
      number of VeA- and LaeA-regulated secondary metabolic gene clusters in A. flavus
      that are postulated to be involved in sclerotial morphogenesis and chemical
      defense. The presence of multiple regulatory factors that control secondary
      metabolism and sclerotial formation suggests that fungi have evolved these
      complex regulatory mechanisms as a means to rapidly adapt chemical responses to
      protect sclerotia from predators, competitors and other environmental stressors. 

PMID- 25762987
TI  - The lung mycobiome: an emerging field of the human respiratory microbiome.
AB  - The lung microbiome, which is believed to be stable or at least transient in
      healthy people, is now considered as a poly-microorganism component contributing
      to disease pathogenesis. Most research studies on the respiratory microbiome have
      focused on bacteria and their impact on lung health, but there is evidence that
      other non-bacterial organisms, comprising the viruses (virome) and fungi
      (mycobiome), are also likely to play an important role in healthy people as well
      as in patients. In the last few years, the lung mycobiome (previously named the
      fungal microbiota or microbiome) has drawn closer attention. There is growing
      evidence that the lung mycobiome has a significant impact on clinical outcome of
      chronic respiratory diseases (CRD) such as asthma, chronic obstructive pulmonary
      disease, cystic fibrosis, and bronchiectasis. Thanks to advances in culture
      independent methods, especially next generation sequencing, a number of fungi not
      detected by culture methods have been molecularly identified in human lungs. It
      has been shown that the structure and diversity of the lung mycobiome vary in
      different populations (healthy and different diseased individuals) which could
      play a role in CRD. Moreover, the link between lung mycobiome and different
      biomes of other body sites, especially the gut, has also been unraveled. By
      interacting with the bacteriome and/or virome, the respiratory mycobiome appears
      to be a cofactor in inflammation and in the host immune response, and therefore
      may contribute to the decline of the lung function and the disease progression.
      In this review, we report the recent limited explorations of the human
      respiratory mycobiome, and discuss the mycobiome's connections with other local
      microbial communities, as well as the relationships with the different biomes of
      other body sites. These studies suggest several outlooks for this understudied
      emerging field, which will certainly call for a renewal of our understanding of
      pulmonary diseases. 

PMID- 25762988
TI  - Histone deacetylase inhibition as an alternative strategy against invasive
      aspergillosis.
AB  - Invasive aspergillosis (IA) is a life-threatening infection due to Aspergillus
      fumigatus and other Aspergillus spp. Drugs targeting the fungal cell membrane
      (triazoles, amphotericin B) or cell wall (echinocandins) are currently the sole
      therapeutic options against IA. Their limited efficacy and the emergence of
      resistance warrant the identification of new antifungal targets. Histone
      deacetylases (HDACs) are enzymes responsible of the deacetylation of lysine
      residues of core histones, thus controlling chromatin remodeling and
      transcriptional activation. HDACs also control the acetylation and activation
      status of multiple non-histone proteins, including the heat shock protein 90
      (Hsp90), an essential molecular chaperone for fungal virulence and antifungal
      resistance. This review provides an overview of the different HDACs in
      Aspergillus spp. as well as their respective contribution to total HDAC activity,
      fungal growth, stress responses, and virulence. The potential of HDAC inhibitors,
      currently under development for cancer therapy, as novel alternative antifungal
      agents against IA is discussed. 

PMID- 25762989
TI  - Long-term forest soil warming alters microbial communities in temperate forest
      soils.
AB  - Soil microbes are major drivers of soil carbon cycling, yet we lack an
      understanding of how climate warming will affect microbial communities. Three
      ongoing field studies at the Harvard Forest Long-term Ecological Research (LTER)
      site (Petersham, MA) have warmed soils 5 degrees C above ambient temperatures for
      5, 8, and 20 years. We used this chronosequence to test the hypothesis that soil
      microbial communities have changed in response to chronic warming. Bacterial
      community composition was studied using Illumina sequencing of the 16S ribosomal
      RNA gene, and bacterial and fungal abundance were assessed using quantitative
      PCR. Only the 20-year warmed site exhibited significant change in bacterial
      community structure in the organic soil horizon, with no significant changes in
      the mineral soil. The dominant taxa, abundant at 0.1% or greater, represented
      0.3% of the richness but nearly 50% of the observations (sequences). Individual
      members of the Actinobacteria, Alphaproteobacteria and Acidobacteria showed
      strong warming responses, with one Actinomycete decreasing from 4.5 to 1%
      relative abundance with warming. Ribosomal RNA copy number can obfuscate
      community profiles, but is also correlated with maximum growth rate or trophic
      strategy among bacteria. Ribosomal RNA copy number correction did not affect
      community profiles, but rRNA copy number was significantly decreased in warming
      plots compared to controls. Increased bacterial evenness, shifting beta
      diversity, decreased fungal abundance and increased abundance of bacteria with
      low rRNA operon copy number, including Alphaproteobacteria and Acidobacteria,
      together suggest that more or alternative niche space is being created over the
      course of long-term warming. 

PMID- 25762990
TI  - Biocatalytic desulfurization of thiophenic compounds and crude oil by newly
      isolated bacteria.
AB  - Microorganisms possess enormous highly specific metabolic activities, which
      enable them to utilize and transform nearly every known chemical class present in
      crude oil. In this context, one of the most studied biocatalytic processes is the
      biodesulfurization (BDS) of thiophenic sulfur-containing compounds such as
      benzothiophene (BT) and dibenzothiophene (DBT) in crude oils and refinery
      streams. Three newly isolated bacterial strains, which were affiliated as
      Rhodococcus sp. strain SA11, Stenotrophomonas sp. strain SA21, and Rhodococcus
      sp. strain SA31, were enriched from oil contaminated soil in the presence of DBT
      as the sole S source. GC-FID analysis of DBT-grown cultures showed consumption of
      DBT, transient formation of DBT sulfone (DBTO2) and accumulation of 2
      hydroxybiphenyl (2-HBP). Molecular detection of the plasmid-borne dsz operon,
      which codes for the DBT desulfurization activity, revealed the presence of dszA,
      dszB, and dszC genes. These results point to the operation of the known 4S
      pathway in the BDS of DBT. The maximum consumption rate of DBT was 11 MUmol/g dry
      cell weight (DCW)/h and the maximum formation rate of 2-HBP formation was 4
      MUmol/g DCW/h. Inhibition of both cell growth and DBT consumption by 2-HBP was
      observed for all isolates but SA11 isolate was the least affected. The isolated
      biocatalysts desulfurized other model DBT alkylated homologs. SA11 isolate was
      capable of desulfurizing BT as well. Resting cells of SA11 exhibited 10%
      reduction in total sulfur present in heavy crude oil and 18% reduction in total
      sulfur present in the hexane-soluble fraction of the heavy crude oil. The
      capabilities of the isolated bacteria to survive and desulfurize a wide range of
      S compounds present in crude oil are desirable traits for the development of a
      robust BDS biocatalyst to upgrade crude oils and refinery streams. 

PMID- 25762991
TI  - Formate hydrogen lyase mediates stationary-phase deacidification and increases
      survival during sugar fermentation in acetoin-producing enterobacteria.
AB  - Two fermentation types exist in the Enterobacteriaceae family. Mixed-acid
      fermenters produce substantial amounts of lactate, formate, acetate, and
      succinate, resulting in lethal medium acidification. On the other hand, 2,3
      butanediol fermenters switch to the production of the neutral compounds acetoin
      and 2,3-butanediol and even deacidify the environment after an initial
      acidification phase, thereby avoiding cell death. We equipped three mixed-acid
      fermenters (Salmonella Typhimurium, S. Enteritidis and Shigella flexneri) with
      the acetoin pathway from Serratia plymuthica to investigate the mechanisms of
      deacidification. Acetoin production caused attenuated acidification during
      exponential growth in all three bacteria, but stationary-phase deacidification
      was only observed in Escherichia coli and Salmonella, suggesting that it was not
      due to the consumption of protons accompanying acetoin production. To identify
      the mechanism, 34 transposon mutants of acetoin-producing E. coli that no longer
      deacidified the culture medium were isolated. The mutations mapped to 16 genes,
      all involved in formate metabolism. Formate is an end product of mixed-acid
      fermentation that can be converted to H2 and CO2 by the formate hydrogen lyase
      (FHL) complex, a reaction that consumes protons and thus can explain medium
      deacidification. When hycE, encoding the large subunit of hydrogenase 3 that is
      part of the FHL complex, was deleted in acetoin-producing E. coli,
      deacidification capacity was lost. Metabolite analysis in E. coli showed that
      introduction of the acetoin pathway reduced lactate and acetate production, but
      increased glucose consumption and formate and ethanol production. Analysis of a
      hycE mutant in S. plymuthica confirmed that medium deacidification in this
      organism is also mediated by FHL. These findings improve our understanding of the
      physiology and function of fermentation pathways in Enterobacteriaceae. 

PMID- 25762992
TI  - Protection of Antarctic microbial communities - 'out of sight, out of mind'.
AB  - Recent advances in molecular biology techniques have shown the presence of
      diverse microbial communities and endemic species in Antarctica. Endemic microbes
      may be a potential source of novel biotechnologically important compounds,
      including, for example, new antibiotics. Thus, the scientific and
      biotechnological value of Antarctic terrestrial microbial habitats can be
      compromised by human visitation to a greater extent than previously realized. The
      ever-increasing human footprint in Antarctica makes consideration of this topic
      more pressing, as the number of locations known to be pristine habitats, where
      increasingly sophisticated cutting-edge research techniques may be used to their
      full potential, declines. Examination of the Protected Areas system of the
      Antarctic Treaty shows that microbial habitats are generally poorly protected. No
      other continent on Earth is dominated to the same degree by microbial species,
      and real opportunities exist to develop new ways of conceptualizing and
      implementing conservation of microbial biogeography on a continental scale. Here
      we highlight potential threats both to the conservation of terrestrial microbial
      ecosystems, and to future scientific research requiring their study. 

PMID- 25762993
TI  - Culturable associated-bacteria of the sponge Theonella swinhoei show tolerance to
      high arsenic concentrations.
AB  - Sponges are potent filter feeders and as such are exposed to high fluxes of toxic
      trace elements, which can accumulate in their body over time. Such is the case of
      the Red Sea sponge Theonella swinhoei, which has been shown to accumulate up to
      8500 mg/Kg of the highly toxicelement arsenic. T. swinhoei is known to harbor a
      multitude of sponge-associated bacteria, so it is hypothesized that the
      associated-bacteria will be tolerant to high arsenic concentration. This study
      also investigates the fate of the arsenic accumulated in the sponge to test if
      the associated-bacteria have an important role in the arsenic accumulation
      process of their host, since bacteria are key players in the natural arsenic
      cycle. Separation of the sponge to sponge cells and bacteria enriched fractions
      showed that arsenic is accumulated by the bacteria. Sponge-associated, arsenic
      tolerant bacteria were cultured in the presence of 5 mM of either arsenate or
      arsenite (equivalent to 6150 mg/Kg arsenic, dry weight). The 54 isolated bacteria
      were grouped to 15 operational taxonomic units (OTUs) and isolates belonging to
      12 OTUs were assessed for tolerance to arsenate at increased concentrations up to
      100 mM. Eight of the 12 OTUs tolerated an order of magnitude increase in the
      concentration of arsenate, and some exhibited external biomineralization of
      arsenic-magnesium salts. The biomineralization of this unique mineral was
      directly observed in bacteria for the first time. These results may provide an
      explanation for the ability of the sponge to accumulate considerable amounts of
      arsenic. Furthermore arsenic-mineralizing bacteria can potentially be used for
      the study of bioremediation, as arsenic toxicity affects millions of people
      worldwide. 

PMID- 25762995
TI  - Methods for extracellular vesicles isolation in a hospital setting.
AB  - The research in extracellular vesicles (EVs) has been rising during the last
      decade. However, there is no clear consensus on the most accurate protocol to
      isolate and analyze them. Besides, most of the current protocols are difficult to
      implement in a hospital setting due to being very time-consuming or to
      requirements of specific infrastructure. Thus, our aim is to compare five
      different protocols (comprising two different medium-speed differential
      centrifugation protocols; commercially polymeric precipitation - exoquick - acid
      precipitation; and ultracentrifugation) for blood and urine samples to determine
      the most suitable one for the isolation of EVs. Nanoparticle tracking analysis,
      flow cytometry, western blot (WB), electronic microscopy, and spectrophotometry
      were used to characterize basic aspects of EVs such as concentration, size
      distribution, cell-origin and transmembrane markers, and RNA concentration. The
      highest EV concentrations were obtained using the exoquick protocol, followed by
      both differential centrifugation protocols, while the ultracentrifugation and
      acid-precipitation protocols yielded considerably lower EV concentrations. The
      five protocols isolated EVs of similar characteristics regarding markers and RNA
      concentration; however, standard protocol recovered only small EVs. EV isolated
      with exoquick presented difficult to be analyzed with WB. The RNA concentrations
      obtained from urine-derived EVs were similar to those obtained from blood-derived
      ones, despite the urine EV concentration being 10-20 times lower. We consider
      that a medium-speed differential centrifugation could be suitable to be applied
      in a hospital setting as it requires the simplest infrastructure and recovers
      higher concentration of EV than standard protocol. A workflow from sampling to
      characterization of EVs is proposed. 

PMID- 25762996
TI  - Transcriptional Factor PU.1 Regulates Decidual C1q Expression in Early Pregnancy
      in Human.
AB  - C1q is the first recognition subcomponent of the complement classical pathway,
      which in addition to being synthesized in the liver, is also expressed by
      macrophages and dendritic cells (DCs). Trophoblast invasion during early
      placentation results in accumulation of debris that triggers the complement
      system. Hence, both early and late components of the classical pathway are widely
      distributed in the placenta and decidua. In addition, C1q has recently been shown
      to significantly contribute to feto-maternal tolerance, trophoblast migration,
      and spiral artery remodeling, although the exact mechanism remains unknown.
      Pregnancy in mice, genetically deficient in C1q, mirrors symptoms similar to that
      of human preeclampsia. Thus, regulated complement activation has been proposed as
      an essential requirement for normal successful pregnancy. Little is known about
      the molecular pathways that regulate C1q expression in pregnancy. PU.1, an Ets
      family transcription factor, is required for the development of hematopoietic
      myeloid lineage immune cells, and its expression is tissue-specific. Recently,
      PU.1 has been shown to regulate C1q gene expression in DCs and macrophages. Here,
      we have examined if PU.1 transcription factor regulates decidual C1q expression.
      We used immune-histochemical analysis, PCR, and immunostaining to localize and
      study the gene expression of PU.1 transcription factor in early human decidua.
      PU.1 was highly expressed at gene and protein level in early human decidual cells
      including trophoblast and stromal cells. Surprisingly, nuclear as well as
      cytoplasmic PU.1 expression was observed. Decidual cells with predominantly
      nuclear PU.1 expression had higher C1q expression. It is likely that nuclear and
      cytoplasmic PU.1 localization has a role to play in early pregnancy via
      regulating C1q expression in the decidua during implantation. 

PMID- 25762994
TI  - Breaking the mold: transcription factors in the anucleate platelet and platelet
      derived microparticles.
AB  - Platelets are small anucleate blood cells derived from megakaryocytes. In
      addition to their pivotal roles in hemostasis, platelets are the smallest, yet
      most abundant, immune cells and regulate inflammation, immunity, and disease
      progression. Although platelets lack DNA, and thus no functional transcriptional
      activities, they are nonetheless rich sources of RNAs, possess an intact
      spliceosome, and are thus capable of synthesizing proteins. Previously, it was
      thought that platelet RNAs and translational machinery were remnants from the
      megakaryocyte. We now know that the initial description of platelets as "cellular
      fragments" is an antiquated notion, as mounting evidence suggests otherwise.
      Therefore, it is reasonable to hypothesize that platelet transcription factors
      are not vestigial remnants from megakaryocytes, but have important, if only
      partly understood functions. Proteins play multiple cellular roles to minimize
      energy expenditure for maximum cellular function; thus, the same can be expected
      for transcription factors. In fact, numerous transcription factors have non
      genomic roles, both in platelets and in nucleated cells. Our lab and others have
      discovered the presence and non-genomic roles of transcription factors in
      platelets, such as the nuclear factor kappa beta (NFkappaB) family of proteins
      and peroxisome proliferator-activated receptor gamma (PPARgamma). In addition to
      numerous roles in regulating platelet activation, functional transcription
      factors can be transferred to vascular and immune cells through platelet
      microparticles. This method of transcellular delivery of key immune molecules may
      be a vital mechanism by which platelet transcription factors regulate
      inflammation and immunity. At the very least, platelets are an ideal model cell
      to dissect out the non-genomic roles of transcription factors in nucleated cells.
      There is abundant evidence to suggest that transcription factors in platelets
      play key roles in regulating inflammatory and hemostatic functions. 

PMID- 25762997
TI  - Macrophages at the fork in the road to health or disease.

PMID- 25762998
TI  - Applying contemporary immunology to elucidate heterologous effects of infant
      vaccines and to better inform maternal-infant immunization practices.

PMID- 25762999
TI  - Metabolic control of B cells: more questions than answers.

PMID- 25763000
TI  - Invasion of shoot apical meristems by Chrysanthemum stunt viroid differs among
      Argyranthemum cultivars.
AB  - Chrysanthemum stunt viroid (CSVd) is a damaging pathogen attacking Argyranthemum
      plants. Our study attempted to reveal distribution patterns of CSVd in shoot
      apical meristems (SAM) and to explore reasons for differential ability of CSVd to
      invade SAM of selected Argyranthemum cultivars. Symptom development was also
      observed on greenhouse-grown Argyranthemum plants. Viroid localization using in
      situ hybridization revealed that the ability of CSVd to invade SAM differed among
      cultivars. In diseased 'Yellow Empire' and 'Butterfly', CSVd was found in all
      tissues including the uppermost cell layers in the apical dome (AD) and the
      youngest leaf primordia 1 and 2. In diseased 'Border Dark Red' and 'Border Pink',
      CSVd was detected in the lower part of the AD and elder leaf primordia, leaving
      the upper part of the AD, and leaf primordia 1 and 2 free of viroid. Histological
      observations and transmission electron microscopy showed similar developmental
      patterns of vascular tissues and plasmodesmata (PD) in the SAM of 'Yellow Empire'
      and 'Border Dark Red', while immunolocalization studies revealed a major
      difference in the number of callose (beta-1, 3-glucan) particles deposited at PD
      in SAM. A lower number of callose particles were found deposited at PD of SAM of
      'Yellow Empire' than 'Border Dark Red'. This difference is most likely
      responsible for the differences in ability of CSVd to invade SAM among
      Argyranthemum cultivars. 

PMID- 25763001
TI  - Long-chain bases, phosphatidic acid, MAPKs, and reactive oxygen species as nodal
      signal transducers in stress responses in Arabidopsis.
AB  - Due to their sessile condition, plants have developed sensitive, fast, and
      effective ways to contend with environmental changes. These mechanisms operate as
      informational wires conforming extensive and intricate networks that are
      connected in several points. The responses are designed as pathways orchestrated
      by molecules that are transducers of protein and non-protein nature. Their
      chemical nature imposes selective features such as specificity, formation rate,
      and generation site to the informational routes. Enzymes such as mitogen
      activated protein kinases and non-protein, smaller molecules, such as long-chain
      bases, phosphatidic acid, and reactive oxygen species are recurrent transducers
      in the pleiotropic responses to biotic and abiotic stresses in plants. In this
      review, we considered these four components as nodal points of converging
      signaling pathways that start from very diverse stimuli and evoke very different
      responses. These pleiotropic effects may be explained by the potentiality that
      every one of these four mediators can be expressed from different sources,
      cellular location, temporality, or magnitude. Here, we review recent advances in
      our understanding of the interplay of these four specific signaling components in
      Arabidopsis cells, with an emphasis on drought, cold and pathogen stresses. 

PMID- 25763002
TI  - Duration and intensity of shade differentially affects mycorrhizal growth- and
      phosphorus uptake responses of Medicago truncatula.
AB  - Plant and fungal partners in arbuscular mycorrhizal symbiosis trade mineral
      nutrients for carbon, with the outcome of this relationship for plant growth and
      nutrition being highly context-dependent and changing with the availability of
      resources as well as with the specific requirements of the different partners.
      Here we studied how the model legume Medicago truncatula, inoculated or not with
      a mycorrhizal fungus Rhizophagus irregularis, responded to a gradient of light
      intensities applied over different periods of time, in terms of growth,
      phosphorus nutrition and the levels of root colonization by the mycorrhizal
      fungus. Short-term (6 d) shading, depending on its intensity, resulted in a rapid
      decline of phosphorus uptake to the shoots of mycorrhizal plants and simultaneous
      accumulation of phosphorus in the roots (most likely in the fungal tissues), as
      compared to the non-mycorrhizal controls. There was, however, no significant
      change in the levels of mycorrhizal colonization of roots due to short-term
      shading. Long-term (38 d) shading, depending on its intensity, provoked a
      multitude of plant compensatory mechanisms, which were further boosted by the
      mycorrhizal symbiosis. Mycorrhizal growth- and phosphorus uptake benefits,
      however, vanished at 10% of the full light intensity applied over a long-term.
      Levels of root colonization by the mycorrhizal fungus were significantly reduced
      by long-term shading. Our results indicate that even short periods of shade could
      have important consequences for the functioning of mycorrhizal symbiosis in terms
      of phosphorus transfer between the fungus and the plants, without any apparent
      changes in root colonization parameters or mycorrhizal growth response, and call
      for more focused research on temporal dynamics of mycorrhizal functioning under
      changing environmental conditions. 

PMID- 25763003
TI  - Non-specific phospholipase C4 mediates response to aluminum toxicity in
      Arabidopsis thaliana.
AB  - Aluminum ions (Al) have been recognized as a major toxic factor for crop
      production in acidic soils. The first indication of the Al toxicity in plants is
      the cessation of root growth, but the mechanism of root growth inhibition is
      largely unknown. Here we examined the impact of Al on the expression, activity,
      and function of the non-specific phospholipase C4 (NPC4), a plasma membrane-bound
      isoform of NPC, a member of the plant phospholipase family, in Arabidopsis
      thaliana. We observed a lower expression of NPC4 using beta-glucuronidase assay
      and a decreased formation of labeled diacylglycerol, product of NPC activity,
      using fluorescently labeled phosphatidylcholine as a phospholipase substrate in
      Arabidopsis WT seedlings treated with AlCl3 for 2 h. The effect on in situ NPC
      activity persisted for longer Al treatment periods (8, 14 h). Interestingly, in
      seedlings overexpressing NPC4, the Al-mediated NPC-inhibiting effect was
      alleviated at 14 h. However, in vitro activity and localization of NPC4 were not
      affected by Al, thus excluding direct inhibition by Al ions or possible
      translocation of NPC4 as the mechanisms involved in NPC-inhibiting effect.
      Furthermore, the growth of tobacco pollen tubes rapidly arrested by Al was
      partially rescued by the overexpression of AtNPC4 while Arabidopsis npc4 knockout
      lines were found to be more sensitive to Al stress during long-term exposure of
      Al at low phosphate conditions. Our observations suggest that NPC4 plays a role
      in both early and long-term responses to Al stress. 

PMID- 25763004
TI  - PGPRs and nitrogen-fixing legumes: a perfect team for efficient Cd
      phytoremediation?
AB  - Cadmium (Cd) is a toxic, biologically non-essential and highly mobile metal that
      has become an increasingly important environmental hazard to both wildlife and
      humans. In contrast to conventional remediation technologies, phytoremediation
      based on legume-rhizobia symbiosis has emerged as an inexpensive decontamination
      alternative which also revitalize contaminated soils due to the role of legumes
      in nitrogen cycling. In recent years, there is a growing interest in
      understanding symbiotic legume-rhizobia relationship and its interactions with
      Cd. The aim of the present review is to provide a comprehensive picture of the
      main effects of Cd in N2-fixing leguminous plants and the benefits of exploiting
      this symbiosis together with plant growth promoting rhizobacteria to boost an
      efficient reclamation of Cd-contaminated soils. 

PMID- 25763005
TI  - Advantages and limitations of shot-gun proteomic analyses on Arabidopsis plants
      with altered MAPK signaling.

PMID- 25763006
TI  - Physiological and proteomic analyses on artificially aged Brassica napus seed.
AB  - Plant seeds lose their viability when they are exposed to long term storage or
      controlled deterioration treatments, by a process known as seed aging. Based on
      previous studies, artificially aging treatments have been developed to accelerate
      the process of seed aging in order to understand its underlying mechanisms. In
      this study, we used Brassica napus seeds to investigate the mechanisms of aging
      initiation. B. napus seeds were exposed to artificially aging treatment (40
      degrees C and 90% relative humidity) and their physio-biochemical characteristics
      were analyzed. Although the treatment delayed germination, it did not increase
      the concentration of cellular reactive oxygen species (ROS). Comparative
      proteomic analysis was conducted among the control and treated seeds at different
      stages of germination. The proteins responded to the treatment were mainly
      involved in metabolism, protein modification and destination, stress response,
      development, and miscellaneous enzymes. Except for peroxiredoxin, no changes were
      observed in the accumulation of other antioxidant enzymes in the artificially
      aged seeds. Increased content of abscisic acid (ABA) was observed in the
      artificially treated seeds which might be involved in the inhibition of
      germination. Taken together, our results highlight the involvement of ABA in the
      initiation of seed aging in addition to the ROS which was previously reported to
      mediate the seed aging process. 

PMID- 25763007
TI  - Reactive sulfur species (RSS): possible new players in the oxidative metabolism
      of plant peroxisomes.

PMID- 25763008
TI  - Epigenetics and autoimmune diseases: the X chromosome-nucleolus nexus.
AB  - Autoimmune diseases occur more often in females, suggesting a key role for the X
      chromosome. X chromosome inactivation, a major epigenetic feature in female cells
      that provides dosage compensation of X-linked genes to avoid overexpression,
      presents special vulnerabilities that can contribute to the disease process.
      Disruption of X inactivation can result in loss of dosage compensation with
      expression from previously sequestered genes, imbalance of gene products, and
      altered endogenous material out of normal epigenetic context. In addition, the
      human X has significant differences compared to other species and these
      differences can contribute to the frequency and intensity of the autoimmune
      disease in humans as well as the types of autoantigens encountered. Here a link
      is demonstrated between autoimmune diseases, such as systemic lupus
      erythematosus, and the X chromosome by discussing cases in which typically non
      autoimmune disorders complicated with X chromosome abnormalities also present
      lupus-like symptoms. The discussion is then extended to the reported spatial and
      temporal associations of the inactive X chromosome with the nucleolus. When
      frequent episodes of cellular stress occur, the inactive X chromosome may be
      disrupted and inadvertently become involved in the nucleolar stress response.
      Development of autoantigens, many of which are at least transiently components of
      the nucleolus, is then described. Polyamines, which aid in nucleoprotein complex
      assembly in the nucleolus, increase further during cell stress, and appear to
      have an important role in the autoimmune disease process. Autoantigenic
      endogenous material can potentially be stabilized by polyamines. This presents a
      new paradigm for autoimmune diseases: that many are antigen-driven and the
      autoantigens originate from altered endogenous material due to episodes of
      cellular stress that disrupt epigenetic control. This suggests that epigenetics
      and the X chromosome are important aspects of autoimmune diseases. 

PMID- 25763009
TI  - Shared genetic variance between obesity and white matter integrity in Mexican
      Americans.
AB  - Obesity is a chronic metabolic disorder that may also lead to reduced white
      matter integrity, potentially due to shared genetic risk factors. Genetic
      correlation analyses were conducted in a large cohort of Mexican American
      families in San Antonio (N = 761, 58% females, ages 18-81 years; 41.3 +/- 14.5)
      from the Genetics of Brain Structure and Function Study. Shared genetic variance
      was calculated between measures of adiposity [(body mass index (BMI; kg/m(2)) and
      waist circumference (WC; in)] and whole-brain and regional measurements of
      cerebral white matter integrity (fractional anisotropy). Whole-brain average and
      regional fractional anisotropy values for 10 major white matter tracts were
      calculated from high angular resolution diffusion tensor imaging data (DTI; 1.7 *
      1.7 * 3 mm; 55 directions). Additive genetic factors explained intersubject
      variance in BMI (heritability, h (2) = 0.58), WC (h (2) = 0.57), and FA (h (2) =
      0.49). FA shared significant portions of genetic variance with BMI in the genu
      (rhoG = -0.25), body (rhoG = -0.30), and splenium (rhoG = -0.26) of the corpus
      callosum, internal capsule (rhoG = -0.29), and thalamic radiation (rhoG = -0.31)
      (all p's = 0.043). The strongest evidence of shared variance was between BMI/WC
      and FA in the superior fronto-occipital fasciculus (rhoG = -0.39, p = 0.020; rhoG
      = -0.39, p = 0.030), which highlights region-specific variation in neural
      correlates of obesity. This may suggest that increase in obesity and reduced
      white matter integrity share common genetic risk factors. 

PMID- 25763010
TI  - Challenges and opportunities in genetic improvement of local livestock breeds.
AB  - Sufficient genetic variation in livestock populations is necessary both for
      adaptation to future changes in climate and consumer demand, and for continual
      genetic improvement of economically important traits. Unfortunately, the current
      trend is for reduced genetic variation, both within and across breeds. The latter
      occurs primarily through the loss of small, local breeds. Inferior production is
      a key driver for loss of small breeds, as they are replaced by high-output
      international transboundary breeds. Selection to improve productivity of small
      local breeds is therefore critical for their long term survival. The objective of
      this paper is to review the technology options available for the genetic
      improvement of small local breeds and discuss their feasibility. Most
      technologies have been developed for the high-input breeds and consequently are
      more favorably applied in that context. Nevertheless, their application in local
      breeds is not precluded and can yield significant benefits, especially when
      multiple technologies are applied in close collaboration with farmers and
      breeders. Breeding strategies that require cooperation and centralized decision
      making, such as optimal contribution selection, may in fact be more easily
      implemented in small breeds. 

PMID- 25763011
TI  - Contribution of oxidative stress to endothelial dysfunction in hereditary
      hemorrhagic telangiectasia.
AB  - Oxidative stress causes endothelial dysfunction and is implicated in the
      pathogenesis of cardiovascular diseases. Our studies suggested that reactive
      oxygen species (ROS) play a crucial role in hereditary hemorrhagic telangiectasia
      (HHT) disease, a vascular dysplasia affecting 1 in 5,000-8,000 people. Mutations
      in endoglin (ENG) and activin receptor-like kinase 1 (ACVRL1) genes are
      responsible for HHT1 and HHT2 and are associated with arteriovenous
      malformations. ENG and ACVRL1 interact with endothelial nitric oxide synthase
      (eNOS) and regulate its activation. Mice heterozygous for these genes (Eng (+/-)
      and Acvrl1 (+/-)) show reduced ENG or ACVRL1 protein levels in endothelial cells
      causing eNOS uncoupling, generation of ROS rather than nitric oxide (NO*),
      leading to impaired NO* mediated vasodilation. ROS production is increased in
      several organs of Eng (+/-) and Acvrl1 (+/-) mice, including lungs, liver, and
      colon, affected in HHT. The major source of increased oxidative stress in these
      tissues is eNOS-derived ROS and not mitochondrial or NADPH oxidase-dependent ROS.
      Eng (+/-) and Acvrl1 (+/-) mice also develop with age signs of pulmonary arterial
      hypertension attributable to eNOS-derived ROS, which was preventable by
      antioxidant treatment. To date, only one pilot study has been carried out in HHT
      patients, and it showed beneficial effects of antioxidant therapy on epistaxis.
      We suggest that more clinical studies are warranted to investigate whether
      antioxidants would prevent, delay or attenuate manifestations of disease in
      individuals with HHT, based on our experimental data in mouse models. 

PMID- 25763013
TI  - Epigenetic consequences of artificial reproductive technologies to the bovine
      imprinted genes SNRPN, H19/IGF2, and IGF2R.
AB  - Animal breeders have made widespread use of assisted reproductive technologies to
      accelerate genetic improvement programs aimed at obtaining more, better and
      cheaper food products. Selection approaches have traditionally focused on
      Mendel's laws of inheritance using parental phenotypic characteristics and
      quantitative genetics approaches to choose the best parents for the next
      generation, regardless of their gender. However, apart from contributing DNA
      sequence variants, male and female gametes carry parental-specific epigenetic
      marks that play key roles during pre- and post-natal development and growth of
      the offspring. We herein review the epigenetic anomalies that are associated with
      artificial reproductive technologies in current use in animal breeding programs.
      For instance, we demonstrate that bovine embryos and fetuses derived by in vitro
      culture and somatic cell nuclear transfer show epigenetic anomalies in the
      differentially methylated regions controlling the expression of some imprinted
      genes. Although these genomic imprinting errors are undetected in the somatic
      tissues after birth, further research is warranted to examine potential germ cell
      transmission of epimutations and the potential risks of reproducing cattle using
      artificial reproductive technologies. 

PMID- 25763012
TI  - Pericytes as targets in hereditary hemorrhagic telangiectasia.
AB  - Defective paracrine Transforming Growth Factor-beta (TGF-beta) signaling between
      endothelial cells and the neighboring mural cells have been thought to lead to
      the development of vascular lesions that are characteristic of Hereditary
      Hemorrhagic Telangiectasia (HHT). This review highlights recent progress in our
      understanding of TGF-beta signaling in mural cell recruitment and vessel
      stabilization and how perturbed TGF-beta signaling might contribute to defective
      endothelial-mural cell interaction affecting vessel functionalities. Our recent
      findings have provided exciting insights into the role of thalidomide, a drug
      that reduces both the frequency and the duration of epistaxis in individuals with
      HHT by targeting mural cells. These advances provide opportunities for the
      development of new therapies for vascular malformations. 

PMID- 25763014
TI  - Live bacterial vaccine vectors: an overview.
AB  - Genetically attenuated microorganisms, pathogens, and some commensal bacteria can
      be engineered to deliver recombinant heterologous antigens to stimulate the host
      immune system, while still offering good levels of safety. A key feature of these
      live vectors is their capacity to stimulate mucosal as well as humoral and/or
      cellular systemic immunity. This enables the use of different forms of
      vaccination to prevent pathogen colonization of mucosal tissues, the front door
      for many infectious agents. Furthermore, delivery of DNA vaccines and immune
      system stimulatory molecules, such as cytokines, can be achieved using these
      special carriers, whose adjuvant properties and, sometimes, invasive capacities
      enhance the immune response. More recently, the unique features and versatility
      of these vectors have also been exploited to develop anti-cancer vaccines, where
      tumor-associated antigens, cytokines, and DNA or RNA molecules are delivered.
      Different strategies and genetic tools are constantly being developed, increasing
      the antigenic potential of agents delivered by these systems, opening fresh
      perspectives for the deployment of vehicles for new purposes. Here we summarize
      the main characteristics of the different types of live bacterial vectors and
      discuss new applications of these delivery systems in the field of vaccinology. 

PMID- 25763015
TI  - Relationship among Shigella spp. and enteroinvasive Escherichia coli (EIEC) and
      their differentiation.
AB  - Shigellosis produces inflammatory reactions and ulceration on the intestinal
      epithelium followed by bloody or mucoid diarrhea. It is caused by enteroinvasive
      E. coli (EIEC) as well as any species of the genus Shigella, namely, S.
      dysenteriae, S. flexneri, S. boydii, and S. sonnei. This current species
      designation of Shigella does not specify genetic similarity. Shigella spp. could
      be easily differentiated from E. coli, but difficulties observed for the EIEC
      Shigella differentiation as both show similar biochemical traits and can cause
      dysentery using the same mode of invasion. Sequencing of multiple housekeeping
      genes indicates that Shigella has derived on several different occasions via
      acquisition of the transferable forms of ancestral virulence plasmids within
      commensal E. coli and form a Shigella-EIEC pathovar. EIEC showed lower expression
      of virulence genes compared to Shigella, hence EIEC produce less severe disease
      than Shigella spp. Conventional microbiological techniques often lead to
      confusing results concerning the discrimination between EIEC and Shigella spp.
      The lactose permease gene (lacY) is present in all E. coli strains but absent in
      Shigella spp., whereas beta-glucuronidase gene (uidA) is present in both E. coli
      and Shigella spp. Thus uidA gene and lacY gene based duplex real-time PCR assay
      could be used for easy identification and differentiation of Shigella spp. from
      E. coli and in particular EIEC. 

PMID- 25763017
TI  - Eucalyptus grandis Hill ex Maiden inoculated with Pisolithus microcarpus (UFSC
      Pt116) in land subject to the sandy process in Southern Brazil.
AB  - Eucalypts is one of the main species used for commercial reforestation in the Rio
      Grande do Sul State, Brazil. This study aimed to evaluate the survival and early
      growth of eucalyptus trees in an area subject to sandy process after three years
      of growth. The Eucalyptus grandis seedlings were grown in a greenhouse,
      inoculated or not with the isolated ectomycorrhizal Pisolithus microcarpus (UFSC
      Pt116), produced in peat or Entisol. After 120 days, the seedlings were
      transplanted to an area subject to the sandy process, in the Sao Francisco de
      Assis city, RS. The plants have been evaluated regarding survival, height, stem
      diameter, nitrogen, phosphorus and potassium levels and total phosphorus,
      inorganic phosphorus, organic phosphorus and wood production on different days
      after planting. The seedlings grown on the Entisol which was inoculated with the
      isolated UFSC-Pt116 presented higher survival rates, height, stem diameter,
      nitrogen concentration and wood production then non-inoculated seedlings.
      Inoculation with ectomycorrhizal fungi enhanced the production of E. grandis
      seedlings in survival rates, height, stem diameter. 

PMID- 25763016
TI  - Regulation of gene expression: cryptic beta-glucoside (bgl) operon of Escherichia
      coli as a paradigm.
AB  - Bacteria have evolved various mechanisms to extract utilizable substrates from
      available resources and consequently acquire fitness advantage over competitors.
      One of the strategies is the exploitation of cryptic cellular functions encoded
      by genetic systems that are silent under laboratory conditions, such as the bgl
      (beta-glucoside) operon of E. coli. The bgl operon of Escherichia coli, involved
      in the uptake and utilization of aromatic beta-glucosides salicin and arbutin, is
      maintained in a silent state in the wild type organism by the presence of
      structural elements in the regulatory region. This operon can be activated by
      mutations that disrupt these negative elements. The fact that the silent bgl
      operon is retained without accumulating deleterious mutations seems paradoxical
      from an evolutionary view point. Although this operon appears to be silent,
      specific physiological conditions might be able to regulate its expression and/or
      the operon might be carrying out function(s) apart from the utilization of
      aromatic beta-glucosides. This is consistent with the observations that the
      activated operon confers a Growth Advantage in Stationary Phase (GASP) phenotype
      to Bgl(+) cells and exerts its regulation on at least twelve downstream target
      genes. 

PMID- 25763018
TI  - Microbial dynamics during azo dye degradation in a UASB reactor supplied with
      yeast extract.
AB  - The present work aimed to investigate the microbial dynamics during the anaerobic
      treatment of the azo dye blue HRFL in bench scale upflow anaerobic sludge bed
      (UASB) reactor operated at ambient temperature. Sludge samples were collected
      under distinct operational phases, when the reactor were stable (low variation of
      color removal), to assess the effect of glucose and yeast extract as source of
      carbon and redox mediators, respectively. Reactors performance was evaluated
      based on COD (chemical oxygen demand) and color removal. The microbial dynamics
      were investigated by PCR-DGGE (Polimerase Chain Reaction - Denaturing Gradient of
      Gel Electrophoresis) technique by comparing the 16S rDNA profiles among samples.
      The results suggest that the composition of microorganisms changed from the
      beginning to the end of the reactor operation, probably in response to the
      presence of azo dye and/or its degradation byproducts. Despite the highest
      efficiency of color removal was observed in the presence of 500 mg/L of yeast
      extract (up to 93%), there were no differences regarding the microbial profiles
      that could indicate a microbial selection by the yeast extract addition. On the
      other hand Methosarcina barkeri was detected only in the end of operation when
      the best efficiencies on color removal occurred. Nevertheless the biomass
      selection observed in the last stages of UASB operation is probably a result of
      the washout of the sludge in response of accumulation of aromatic amines which
      led to tolerant and very active biomass that contributed to high efficiencies on
      color removal. 

PMID- 25763019
TI  - Bacterial diversity in relatively pristine and anthropogenically-influenced
      mangrove ecosystems (Goa, India).
AB  - To appreciate differences in benthic bacterial community composition at the
      relatively pristine Tuvem and the anthropogenically-influenced Divar mangrove
      ecosystems in Goa, India, parallel tag sequencing of the V6 region of 16S rDNA
      was carried out. We hypothesize that availability of extraneously-derived
      anthropogenic substrates could act as a stimulatant but not a deterrent to
      promote higher bacterial diversity at Divar. Our observations revealed that the
      phylum Proteobacteria was dominant at both locations comprising 43-46% of total
      tags. The Tuvem ecosystem was characterized by an abundance of members belonging
      to the class Deltaproteobacteria (21%), ~ 2100 phylotypes and 1561 operational
      taxonomic units (OTUs) sharing > 97% similarity. At Divar, the
      Gammaproteobacteria were ~ 2* higher (17%) than at Tuvem. A more diverse
      bacterial community with > 3300 phylotypes and > 2000 OTUs mostly belonging to
      Gammaproteobacteria and a significantly higher DNT (n = 9, p < 0.001, df = 1)
      were recorded at Divar. These findings suggest that the quantity and quality of
      pollutants at Divar are perhaps still at a level to maintain high diversity.
      Using this technique we could show higher diversity at Divar with the possibility
      of Gammaproteobacteria contributing to modulating excess nitrate. 

PMID- 25763020
TI  - Optimization of the production of mycorrhizal inoculum on substrate with organic
      fertilizer.
AB  - The system for production of inoculum of arbuscular mycorrhizal fungi (AMF) using
      sand and vermiculite irrigated with nutrient solution is promising. However,
      organic amendments added to the substrate can stimulate sporulation of AMF and
      replace the nutrient solution. The aim of this study was to maximize the
      production of AMF (Acaulospora longula, Claroideoglomus etunicatum, Dentiscutata
      heterogama and Gigaspora albida) using selected organic substrates (vermicompost,
      coir dust and Tropstrato) together with sand and vermiculite. The production of
      spores varied among the tested AMF and according to the organic source added to
      the substrate. The vermicompost promoted higher sporulation of A. longula in
      relation to the other AMF and substrates. The Tropstrato inhibited the
      sporulation of D. heterogama while the reproduction of C. etunicatum was not
      affected by the organic compounds. The inoculum of A. longula also showed a high
      number of infective propagules and promoted biomass accumulation in maize plants.
      The system of inoculum production using sand and vermiculite + 10% vermicompost
      favors the production of infective inoculum of A. longula with the fungus
      benefiting growth of corn plants.

PMID- 25763021
TI  - Poly R decolorization and APPL production by Streptomyces violaceoruber and
      Streptomyces spiroverticillatus.
AB  - Two mesophilic streptomycetes (S. violaceoruber and S. spiroverticillatus) were
      selected to study their Poly R-478 decolorization ability and lignocellulose
      solubilizing activity. Both strains were able to degrade Poly R-478 dye and
      ferulic acid during growth on a minimal salts medium. The Poly R-478 decolorizing
      activities of both strains were induced by adding different carbon sources to the
      culture media. S. violaceoruber could decolorize 63% of Poly R-478 after 24 h.
      Both strains could solubilize straw and produce acid-precipitable polymeric
      lignin (APPL) with different efficiency. From the major extracellular enzymes
      recovery of both strains on rice and wheat straw, we can predicate that the
      biodegradation process was partial indicating a possible utilization in
      biological delignification. 

PMID- 25763022
TI  - Large scale distribution of bacterial communities in the upper Parana River
      floodplain.
AB  - A bacterial community has a central role in nutrient cycle in aquatic habitats.
      Therefore, it is important to analyze how this community is distributed
      throughout different locations. Thirty-six different sites in the upper Parana
      River floodplain were surveyed to determine the influence of environmental
      variable in bacterial community composition. The sites are classified as rivers,
      channels, and floodplain lakes connected or unconnected to the main river
      channel. The bacterial community structure was analyzed by fluorescent in situ
      hybridization (FISH) technique, based on frequency of the main domains Bacteria
      and Archaea, and subdivisions of the phylum Proteobacteria (Alpha-proteobacteria,
      Beta-proteobacteria, Gamma-proteobacteria) and the Cytophaga-Flavobacterium
      cluster. It has been demonstrated that the bacterial community differed in
      density and frequency of the studied groups. And these differences responded to
      distinct characteristics of the three main rivers of the floodplain as well as to
      the classification of the environments found in this floodplain. We conclude that
      dissimilarities in the bacterial community structure are related to environmental
      heterogeneity, and the limnological variables that most predicted bacterial
      communities in the upper Parana River floodplain was total and ammoniacal
      nitrogen, orthophosphate and chlorophyll-a. 

PMID- 25763023
TI  - Role of wild birds as carriers of multi-drug resistant Escherichia coli and
      Escherichia vulneris.
AB  - Emergence and distribution of multi-drug resistant (MDR) bacteria in environments
      pose a risk to human and animal health. A total of 82 isolates of Escherichia
      spp. were recovered from cloacal swabs of migrating and non-migrating wild birds.
      All bacterial isolates were identified and characterized morphologically and
      biochemically. 72% and 50% of isolates recovered from non-migrating and migrating
      birds, respectively, showed positive congo red dye binding (a virulence factor).
      Also, hemolysin production (a virulence factor) was showed in 8% of isolates
      recovered from non-migrating birds and 75% of isolates recovered from migrating
      birds. All isolates recovered from non-migrating birds were found resistant to
      Oxacillin while all isolates recovered from migrating birds demonstrated
      resistance to Oxacillin, Chloramphenicol, Oxytetracycline and Lincomycin. Some
      bacterial isolates recovered from non-migrating birds and migrating birds
      exhibited MDR phenotype. The MDR isolates were further characterized by API 20E
      and 16S rRNA as E. coli and E. vulneris. MDR Escherichia isolates contain ~1-5
      plasmids of high-molecular weights. Accordingly, wild birds could create a
      potential threat to human and animal health by transmitting MDR bacteria to water
      streams and other environmental sources through their faecal residues, and to
      remote regions by migration. 

PMID- 25763024
TI  - Assessment of cellulolytic microorganisms in soils of Nevados Park, Colombia.
AB  - A systematized survey was conducted to find soil-borne microbes that degrade
      cellulose in soils from unique ecosystems, such as the Superparamo, Paramo, and
      the High Andean Forest in the Nevados National Natural Park (NNNP), Colombia.
      These high mountain ecosystems represent extreme environments, such as high
      levels of solar radiation, low atmospheric pressure, and extreme daily changes in
      temperature. Cellulolytic activity of the microorganisms was evaluated using
      qualitative tests, such as growth in selective media followed by staining with
      congo red and iodine, and quantitative tests to determine the activity of
      endoglucanase, beta-glucosidase, exoglucanase, and total cellulase.
      Microorganisms were identified using molecular markers, such as the 16S rRNA gene
      for bacteria and the internal transcribed spacer region (ITS) of ribosomal DNA
      for fungi. Multivariate statistical analysis (MVA) was used to select
      microorganisms with high cellulolytic capacity. A total of 108 microorganisms
      were isolated from the soils and, in general, the enzymatic activities of fungi
      were higher than those of bacteria. Our results also found that none of the
      organisms studied were able to degrade all the components of the cellulose and it
      is therefore suggested that a combination of bacteria and/or fungi with various
      enzymatic activities be used to obtain high total cellulolytic activity. This
      study gives an overview of the potential microorganism that could be used for
      cellulose degradation in various biotechnological applications and for
      sustainable agricultural waste treatment. 

PMID- 25763025
TI  - Antibacterial properties of silver nanoparticles synthesized by marine
      Ochrobactrum sp.
AB  - Metal nanoparticle synthesis is an interesting area in nanotechnology due to
      their remarkable optical, magnetic, electrical, catalytic and biomedical
      properties, but there needs to develop clean, non-toxic and environmental
      friendly methods for the synthesis and assembly of nanoparticles. Biological
      agents in the form of microbes have emerged up as efficient candidates for
      nanoparticle synthesis due to their extreme versatility to synthesize diverse
      nanoparticles with varying size and shape. In the present study, an eco favorable
      method for the biosynthesis of silver nanoparticles using marine bacterial
      isolate has been attempted. Very interestingly, molecular identification proved
      it as a strain of Ochrobactrum anhtropi. In addition, the isolate was found to
      have the potential to form silver nanoparticles intracellularly at room
      temperature within 24 h. The biosynthesized silver nanoparticles were
      characterized by UV-Vis spectroscopy, transmission electron microscope (TEM) and
      scanning electron microscope (SEM). The UV-visible spectrum of the aqueous medium
      containing silver nanoparticles showed a peak at 450 nm corresponding to the
      plasmon absorbance of silver nanoparticles. The SEM and TEM micrographs revealed
      that the synthesized silver nanoparticles were spherical in shape with a size
      range from 38 nm - 85 nm. The silver nanoparticles synthesized by the isolate
      were also used to explore its antibacterial potential against pathogens like
      Salmonella Typhi, Salmonella Paratyphi, Vibrio cholerae and Staphylococcus
      aureus. 

PMID- 25763026
TI  - Screening and optimization of low-cost medium for Pseudomonas putida Rs-198
      culture using RSM.
AB  - The plant growth-promoting rhizobacterial strain Pseudomonas putida Rs-198 was
      isolated from salinized soils from Xinjiang Province. We optimized the
      composition of the low-cost medium of P. putida Rs-198 based on its bacterial
      concentration, as well as its phosphate-dissolving and indole acetic acid (IAA)
      producing capabilities using the response surface methodology (RSM), and a
      mathematical model was developed to show the effect of each medium component and
      its interactions on phosphate dissolution and IAA production. The model predicted
      a maximum phosphate concentration in medium containing 63.23 mg/L inorganic
      phosphate with 49.22 g/L corn flour, 14.63 g/L soybean meal, 2.03 g/L K2HPO4,
      0.19 g/L MnSO4 and 5.00 g/L NaCl. The maximum IAA concentration (18.73 mg/L) was
      predicted in medium containing 52.41 g/L corn flour, 15.82 g/L soybean meal, 2.40
      g/L K2HPO4, 0.17 g/L MnSO4 and 5.00 g/L NaCl. These predicted values were also
      verified through experiments, with a cell density of 10(13) cfu/mL, phosphate
      dissolution of 64.33 mg/L, and IAA concentration of 18.08 mg/L. The excellent
      correlation between predicted and measured values of each model justifies the
      validity of both the response models. The study aims to provide a basis for
      industrialized fermentation using P. putida Rs-198.

PMID- 25763027
TI  - Biotransformation of Tributyltin chloride by Pseudomonas stutzeri strain DN2.
AB  - A bacterial isolate capable of utilizing tributyltin chloride (TBTCl) as sole
      carbon source was isolated from estuarine sediments of west coast of India and
      identified as Pseudomonas stutzeri based on biochemical tests and Fatty acid
      methyl ester (FAME) analysis. This isolate was designated as strain DN2. Although
      this bacterial isolate could resist up to 3 mM TBTCl level, it showed maximum
      growth at 2 mM TBTCl in mineral salt medium (MSM). Pseudomonas stutzeri DN2
      exposed to 2 mM TBTCl revealed significant alteration in cell morphology as
      elongation and shrinkage in cell size along with roughness of cell surface. FTIR
      and NMR analysis of TBTCl degradation product extracted using chloroform and
      purified using column chromatography clearly revealed biotransformation of TBTCl
      into Dibutyltin dichloride (DBTCl2) through debutylation process. Therefore,
      Pseudomonas stutzeri strain DN2 may be used as a potential bacterial strain for
      bioremediation of TBTCl contaminated aquatic environmental sites.

PMID- 25763028
TI  - Occurrence and molecular characterization of Cucumber green mottle mosaic virus
      in cucurbit crops of KPK, Pakistan.
AB  - Field survey of the cucurbit crops revealed a high incidence of Cucumber green
      mottle mosaic virus (CGMMV) in Khyber Pakhtunkhwa Province (KPK), Pakistan. Among
      the seven districts surveyed, average percent incidence of CGMMV was recorded up
      to 58.1% in district Nowshera, followed by 51.1% in district Charsada, 40.5% in
      district Swabi and 37.3% in district Mardan. In Swat and Dir districts average
      incidence CGMMV was recorded upto 31.2% and 29.4%, respectively. Among the
      different crops highest incidence in plain areas of KPK was recorded in bottle
      gourd (59.3%) followed by 56.3% in Squash, 54.5% in Pumpkin, 45.5% in Melon,
      41.7% in Cucumber and 29.9% in Sponge gourd. In Northern hilly areas highest
      incidence of CGMMV (52.9%) was observed in pumpkin, followed by 49.6% in bottle
      gourd, 47.3% in squash, 45.1% in Melon 42.3% in cucumber and 41.6% in sponge
      gourd. Little variability was observed in the coat protein amino acid sequence
      identities of CGMMV Pakistan isolate, when compared with other reported isolates.

PMID- 25763029
TI  - Molecular identification of the occurrence of magnetotactic bacteria in fresh
      water sediments (Czech Republic).
AB  - Magnetotactic bacteria (MTB) are of considerable interest because of their
      importance in the manufacture of various bioinspired materials. In order to find
      out the status of magnetotactic bacteria at three different sediment in Czech
      Republic, samples collected from both standing and running freshwaters were
      subjected to molecular diversity analysis by using 16S rRNA gene approach. Total
      community DNA from sediment sample was isolated and used for PCR, cloning and
      sequence analysis. Of the 24 analyzed sequences, six clones are closely related
      to Magnetobacterium sp. affiliated with the Nitrospira phylum which showed the
      dominance of Magnetobacterium phylotypes in the sample. This study will provide
      useful insight about the community structure of MTB in this particular
      geographical region. However more detailed and specific studies are warranted in
      order to properly assess the community structure of MTB's in fresh water
      sediments. 

PMID- 25763030
TI  - Efficiency of treatments for controlling Trichoderma spp during spawning in
      cultivation of lignicolous mushrooms.
AB  - Trichoderma spp is the cause of the green mold disease in mushroom cultivation
      production. Many disinfection treatments are commonly applied to lignocellulose
      substrates to prevent contamination. Mushroom growers are usually worried about
      the contaminations that may occur after these treatments during handling or
      spawning. The aim of this paper is to estimate the growth of the green mold
      Trichoderma sp on lignocellulose substrates after different disinfection
      treatments to know which of them is more effective to avoid contamination during
      spawning phase. Three different treatments were assayed: sterilization (121 
      degrees C), immersion in hot water (60 and 80  degrees C), and immersion in
      alkalinized water. Wheat straw, wheat seeds and Eucalyptus or Populus sawdust
      were used separately as substrates. After the disinfection treatments, bagged
      substrates were sprayed with 3 mL of suspension of conidia of Trichoderma sp
      (10(5) conidia/mL) and then separately spawned with Pleurotus ostreatus or
      Gymnopilus pampeanus. The growth of Trichoderma sp was evaluated based on a
      qualitative scale. Trichoderma sp could not grow on non-sterilized substrates.
      Immersions in hot water treatments and immersion in alkalinized water were also
      unfavorable treatments for its growth. Co- cultivation with mushrooms favored
      Trichoderma sp growth. Mushroom cultivation disinfection treatments of
      lignocellulose substrates influence on the growth of Trichoderma sp when
      contaminations occur during spawning phase. The immersion in hot water at 60 
      degrees C for 30 min or in alkalinized water for 36 h, are treatments which
      better reduced the contaminations with Trichoderma sp during spawning phase for
      the cultivation of lignicolous species. 

PMID- 25763031
TI  - Plant growth promoting capability and genetic diversity of bacteria isolated from
      mud volcano and lime cave of Andaman and Nicobar Islands.
AB  - Twenty four bacterial strains from four different regions of mud volcano and lime
      cave were isolated to estimate their diversity, plant growth promoting and
      biocontrol activities to use them as inoculant strains in the fields. An
      excellent antagonistic effect against four plant pathogens and plant growth
      promoting properties such as IAA production, HCN production, phosphate
      solubilization, siderophore production, starch hydrolysis and hydrolytic enzymes
      syntheses were identified in OM5 (Pantoea agglomerans) and EM9 (Exiguobacterium
      sp.) of 24 studied isolates. Seeds (Chili and tomato) inoculation with plant
      growth promoting strains resulted in increased percentage of seedling emergence,
      root length and plant weight. Results indicated that co-inoculation gave a more
      pronounced effects on seedling emergence, secondary root numbers, primary root
      length and stem length, while inoculation by alone isolate showed a lower effect.
      Our results suggest that the mixed inocula of OM5 and EM9 strains as
      biofertilizers could significantly increase the production of food crops in
      Andaman archipelago by means of sustainable and organic agricultural system. 

PMID- 25763032
TI  - Gram-negative intestinal indigenous microbiota from two Siluriform fishes in a
      tropical reservoir.
AB  - The Gram-negative intestinal microbiota of Hypostomus auroguttatus and Pimelodus
      maculatus, a detritivorous and an omnivorous fish species, respectively, were
      compared between fishes from the reservoir and the stretch of the river below the
      dam of the Funil hydroelectric plant, Rio de Janeiro, Brazil. Four selective
      culture media were used under aerobic and two under anaerobic conditions. The
      omnivorous species had microbiota with higher population levels compared to the
      detritivorous species. The number of morphotypes and population levels of total
      bacteria, vibrio and Bacteroides tended to be higher in summer and autumn in the
      reservoir, and not different in the river. The number of morphotypes of
      enterobacteria and total bacteria were higher in the lotic environment compared
      with the lentic one. The bacteria Aeromonas hydrophila and Plesiomonas
      shigelloides and the obligate anaerobic Fusobacterium mortiferum were the most
      frequently identified microorganisms in the intestine of both H. auroguttatus and
      P. maculatus. Both season and habitat influenced the Gram-negative intestinal
      microbiota of H. auroguttatus and P. maculatus. Environmental factors influenced
      the Gram-negative intestinal microbiota of both species with possible impact on
      the interrelationship between the fishes and their digestive ecosystem, although
      the gut microbiota composition of fishes may result from host-specific selective
      pressures within the gut. 

PMID- 25763033
TI  - Molecular characterization of a Xylanase-producing fungus isolated from fouled
      soil.
AB  - Xylanase (EC 3. 2. 1. 8), hydrolyzes xylo-oligosaccharides into D-xylose and
      required for complete hydrolysis of native cellulose and biomass conversion. It
      has broad range of applications in the pulp and paper, pharmaceutical and Agri
      food industries. Fifty fungal species were isolated from the fouled soil around
      an oil refinery and screened for the production of xylanase enzyme by enrichment
      culture techniques. The isolated fungal strain was identified as Hypocrea lixii
      SS1 based on the results of biochemical tests and 18s rRNA sequencing. The
      phylogenetic tree was constructed using the MEGA 5 software. Further, Hypocrea
      lixii SS1 was tested for the ability to utilize the sunflower oil sludge (waste
      from the oil industry) as the sole carbon source for xylanase production. The
      growth characteristics of Hypocrea lixii SS1 were also studied and maximum growth
      was found on the 7(th) day of incubation. The fungus showed a remarkable xylanase
      production of 38.9 U/mL. Xylanase was purified using a combination of 0-50%
      NH4SO2 precipitation, DEAE-sepharose and Sephacryl S-200 chromatography. Single
      peak obtained in RP-HPLC confirms the purity of xylanase. Further the enzyme
      produced was affirmed as xylanase with its molecular weight (29 kDa) using SDS
      PAGE.

PMID- 25763034
TI  - Further characterization of o-nitrobenzaldehyde degrading bacterium Pseudomonas
      sp. ONBA-17 and deduction on its metabolic pathway.
AB  - A previously reported o-nitrobenzaldehyde (ONBA) degrading bacterium Pseudomonas
      sp. ONBA-17 was further identified and characterized. Based on results of DNA
      base composition and DNA-DNA hybridization, the strain was identified as P.
      putida. Its degradation effect enhanced with increase of inoculum amount and no
      lag phase was observed. Higher removal rate was achieved under shaking
      conditions. All tested ONBA with different initial concentrations could be
      completely degraded within 5 d. In addition, degradative enzyme(s) involved was
      confirmed as intra-cellular distributed and constitutively expressed. Effects of
      different compounds on relative activity of degradative enzyme(s) within cell
      free extract were also evaluated. Finally, 2-nitrobenzoic acid and 2, 3
      dihydroxybenzoic acid were detected as metabolites of ONBA degradation by P.
      putida ONBA-17, and relevant metabolic pathway was preliminary proposed. This
      study might help with future research in better understanding of nitroaromatics
      biodegradation. 

PMID- 25763035
TI  - Isolation and characterization of arsenic resistant bacteria from wastewater.
AB  - The present study proposed the isolation of arsenic resistant bacteria from
      wastewater. Only three bacterial isolates (MNZ1, MNZ4 and MNZ6) were able to grow
      in high concentrations of arsenic. The minimum inhibitory concentrations of
      arsenic against MNZ1, MNZ4 and MNZ6 were 300 mg/L, 300 mg/L and 370 mg/L
      respectively. The isolated strains showed maximum growth at 37  degrees C and at
      7.0 pH in control but in arsenite stress Luria Bertani broth the bacterial growth
      is lower than control. All strains were arsenite oxidizing. All strains were
      biochemically characterized and ribotyping (16S rRNA) was done for the purpose of
      identification which confirmed that MNZ1 was homologous to Enterobacter sp. while
      MNZ4 and MNZ6 showed their maximum homology with Klebsiella pneumoniae. The
      protein profiling of these strains showed in arsenic stressed and non stressed
      conditions, so no bands of induced proteins appeared in stressed conditions. The
      bacterial isolates can be exploited for bioremediation of arsenic containing
      wastes, since they seem to have the potential to oxidize the arsenite (more
      toxic) into arsenate (less toxic) form. 

PMID- 25763036
TI  - Quick stimulation of Alcanivorax sp. by bioemulsificant EPS2003 on microcosm oil
      spill simulation.
AB  - Oil spill microcosms experiments were carried out to evaluate the effect of
      bioemulsificant exopolysaccharide (EPS2003) on quick stimulation of
      hydrocarbonoclastic bacteria. Early hours of oil spill, were stimulated using an
      experimental seawater microcosm, supplemented with crude oil and EPS2003
      (SW+OIL+EPS2003); this system was monitored for 2 days and compared to control
      microcosm (only oil-polluted seawater, SW+OIL). Determination of bacterial
      abundance, heterotrophic cultivable and hydrocarbon-degrading bacteria were
      carried out. Community composition of marine bacterioplankton was determined by
      16S rRNA gene clone libraries. Data obtained indicated that bioemulsificant
      addition stimulated an increase of total bacterial abundance and, in particular,
      selection of bacteria related to Alcanivorax genus; confirming that EPS2003 could
      be used for the dispersion of oil slicks and could stimulate the selection of
      marine hydrocarbon degraders thus increasing bioremediation process.

PMID- 25763037
TI  - Green Synthesis of AgNPs Stabilized with biowaste and their antimicrobial
      activities.
AB  - In the present study, rapid reduction and stabilization of Ag+ ions with
      different NaOH molar concentration (0.5 mM, 1.0 mM and 1.5 mM) has been carried
      out in the aqueous solution of silver nitrate by the bio waste peel extract of
      P.granatum. Generally, chemical methods used for the synthesis of AgNPs are quite
      toxic, flammable and have adverse effect in medical application but green
      synthesis is a better option due to eco-friendliness, non-toxicity and safe for
      human. Stable AgNPs were synthesized by treating 90 mL aqueous solution of 2 mM
      AgNO3 with the 5 mL plant peels extract (0.4% w/v) at different NaOH
      concentration (5 mL). The synthesized AgNPs were characterized by UV-Vis
      spectroscopy, TEM and SEM. Further, antimicrobial activities of AgNPs were
      performed on Gram positive i.e. Staphylococcus aureus, Bacillus subtilius and
      Gram negative i.e. E. coli, Pseudomonas aeruginosa bacteria. The AgNPs
      synthesized at 1.5 mM NaOH concentration had shown maximum zone of inhibition
      (ZOI) i.e. 49 +/- 0.64 in E. coli, whereas Pseudomonas aeruginosa, Staphylococcus
      aureus and Bacillus subtilius had shown 40 +/- 0.29 mm, 28 +/- 0.13 and 42 +/-
      0.49 mm ZOI respectively. The MIC value of 30 MUg/mL observed for E. coli
      Whereas, Staphylococcus aureus, Bacillus subtilius and Pseudomonas aeruginosa had
      shown 45 MUg/mL, 38 MUg/mL, 35 MUg/mL respectively. The study revealed that AgNPs
      had shown significant antimicrobial activity as compared to Streptomycin.

PMID- 25763038
TI  - Cultivable endophytic bacteria from leaf bases of Agave tequilana and their role
      as plant growth promoters.
AB  - Agave tequilana Weber var. 'Azul' is grown for the production of tequila, inulin
      and syrup. Diverse bacteria inhabit plant tissues and play a crucial role for
      plant health and growth. In this study culturable endophytic bacteria were
      extracted from leaf bases of 100 healthy Agave tequilana plants. In plant tissue
      bacteria occurred at mean population densities of 3 million CFU/g of fresh plant
      tissue. Three hundred endophytic strains were isolated and 16s rDNA sequences
      grouped the bacteria into eight different taxa that shared high homology with
      other known sequences. Bacterial endophytes were identified as Acinectobacter
      sp., A. baumanii, A. bereziniae, Cronobacter sakazakii, Enterobacter hormaechei,
      Bacillus sp. Klebsiella oxytoca, Pseudomonas sp., Enterococcus casseliflavus,
      Leuconostoc mesenteroides subsp. mesenteroides and Gluconobacter oxydans.
      Isolates were confirmed to be plant growth promoting bacteria (PGPB) by their
      capacities for nitrogen fixation, auxin production, phosphate solubilization, or
      antagonism against Fusarium oxysporum AC132. E. casseliflavus JM47 and K. oxytoca
      JM26 secreted the highest concentrations of IAA. The endophyte Acinectobacter sp.
      JM58 exhibited the maximum values for nitrogen fixation and phosphate
      solubilization index (PSI). Inhibition of fungi was found in Pseudomonas sp. JM9p
      and K. oxytoca JM26. Bacterial endophytes show promise for use as bio-inoculants
      for agave cultivation. Use of endophytes to enhance cultivation of agave may be
      particularly important for plants produced by micropropagation techniques, where
      native endophytes may have been lost. 

PMID- 25763039
TI  - Volatile compounds of Lamiaceae exhibit a synergistic antibacterial activity with
      streptomycin.
AB  - Bacterial infections cause thousands of deaths in the world every year. In most
      cases, infections are more serious because the patient is already weakened, and
      often, the bacteria are already resistant to the antibiotics used. Counterparting
      this negative scenario, the interest in medicinal plants as an alternative to the
      synthetic antimicrobial drugs is blossoming worldwide. In the present work, we
      identified the volatile compounds of ethanol extracts of Melissa officinalis,
      Mentha sp., Ocimum basilicum, Plectranthus barbatus, and Rosmarinus officinalis
      by gas chromatography/mass spectrometry (GC/MS). Also was evaluated antimicrobial
      activity of ethanol extracts against 6 bacteria of clinical interest, and was
      tested the interaction of these extracts with a commercial antibiotic
      streptomycin. Phytol was a compound identified in all extracts by GC/MS, being
      majoritary component in Plectranthus barbatus and Rosmarinus officinalis. The
      Gram-positive bacteria were more sensitive to ethanol extracts, and Plectranthus
      barbatus and Rosmarinus officinalis were the most active extracts. Ethanol
      extracts exhibited a synergetic effect with streptomycin. These results encourage
      additional studies, in order to evaluate the possibilities of using ethanol
      extracts of Lamiaceae family as natural source for antibacterial activity. 

PMID- 25763040
TI  - Antifungal activity against Cryptococcus neoformans strains and genotoxicity
      assessment in human leukocyte cells of Euphorbia tirucalli L.
AB  - In the last times, focus on plant research has increased all over the world.
      Euphorbia tirucalli L., a plant known popularly as Aveloz, and originally used in
      Africa, has been drawing attention for its use in the United States and Latin
      America, both for use as an ornamental plant and as a medicinal plant. E.
      tirucalli L. is a member of the family Euphorbiaceae and contains many
      diterpenoids and triterpenoids, in particular phorbol esters, apparently the main
      constituent of this plant, which are assumed to be responsible for their
      activities in vivo and in vitro. The in vitro antifungal activities of Euphorbia
      tirucalli (L.) against opportunistic yeasts were studied using microbroth
      dilution assay. The results showed that aqueous extract and latex preparation
      were effective against ten clinical strains of Cryptococcus neoformans in vitro
      (Latex and extract MIC range of 3.2 - > 411 MUg/mL). Aiming the safe use in
      humans, the genotoxic effects of E. tirucalli were evaluated in human leukocytes
      cells. Our data show that both aqueous extract and latex preparation have no
      genotoxic effect in human leukocytes cells in vitro. Although the results cannot
      be extrapolated by itself for use in vivo, they suggest a good perspective for a
      therapeutic application in future. In conclusion, our results show that the
      aqueous extract and latex preparation from E. tirucalli L. are antifungal agents
      effectives against several strains of C. neoformans and do not provoke DNA damage
      in human leukocyte cells, considering the concentrations tested. 

PMID- 25763041
TI  - Immunological assays employed for the elucidation of an histoplasmosis outbreak
      in Sao Paulo, SP.
AB  - Several reports showed outbreaks of histoplasmosis acquired while bat-inhabited
      caves were visited by tourists, miners or researchers. We evaluated the
      performance of double immunodifusion (DI) and immunoblotting (IB) assays,
      employed for the histoplasmosis outbreak elucidation occurred in Vale do Paraiba,
      Sao Paulo. The existence of epidemiologic link, four patients with clinical signs
      suggestive of histoplasmosis and mycological confirmation has made that all 35
      individuals involved to the cave visit were subjected to serological evaluation.
      By DI, we observed reactivity against H. capsulatum antigen in a single serum
      examined nearly 20 days after exposure to fungal propagules. On the other hand,
      IB showed reactivity against H and M fractions in 50% of samples evaluated. The
      analysis of the second sample batch, collected two months after the exposure
      showed that 96.7% were reactive by DI with antibodies titers ranging from 1 to 16
      and 100% of reactivity against H and M fractions, by IB, suggesting an acute
      infection. The analysis of the overall agreement between the methods showed to be
      reasonable (kappa = 0.37). This study confirms the importance and efficacy of
      more sensitive methodologies, such as IB assay, to early elucidation of disease,
      especially in cases of patients without mycological information. 

PMID- 25763042
TI  - Validation of a real-time PCR assay for the molecular identification of
      Mycobacterium tuberculosis.
AB  - Mycobacterium tuberculosis is the major cause of tuberculosis in humans. This
      bacillus gained prominence with the occurrence of HIV, presenting itself as an
      important opportunistic infection associated with acquired immunodeficiency
      syndrome (AIDS). The current study aimed to develop a real-time PCR using Eva
      Green technology for molecular identification of M. tuberculosis isolates. The
      primers were designed to Rv1510 gene. Ninety nine samples of M. tuberculosis and
      sixty samples of M. bovis were tested and no sample of the bovine bacillus was
      detected by the qPCR. Statistical tests showed no difference between the qPCR and
      biochemical tests used to identify the Mycobacterium tuberculosis. The
      correlation between tests was perfect with Kappa index of 1.0 (p < 0.001, CI =
      0.84 - 1.0). The diagnostic sensitivity and specificity were 100% (CI = 95.94% -
      100%) and 100% (CI = 93.98% - 100%). This qPCR was developed with the goal of
      diagnosing the bacillus M. tuberculosis in samples of bacterial suspension. TB
      reference laboratories (health and agriculture sectors), public health programs
      and epidemiological studies probably may benefit from such method. 

PMID- 25763044
TI  - Treatment with some anti-inflammatory drugs reduces germ tube formation in
      Candida albicans strains.
AB  - Candida albicans is an opportunistic dimorphic fungus that inhabits various host
      mucosal sites. It can cause both superficial and serious systemic disease.
      Conversion from the yeast to the hyphal form has been associated with increased
      virulence and mucosal invasiveness. The aim of this study was to investigate the
      effect of sodium diclofenac and aspirin on germs tube formation of different
      Candida albicans strains. Prostaglandins may play an important role in fungal
      colonization. Nonsteroidal anti-inflammatory drugs are inhibitors of the
      cyclooxygenase isoenzymes. These drugs specifically block the biosynthesis of
      mammalian prostaglandins by inhibiting one or both of cyclooxygenase isoenzymes.
      In tests for germ tube formation sodium diclofenac reduced the filamentation to
      the 12.5%- 5.1%. In the presence of aspirin the filamentation was reduced up to
      85-45% depending on the tested strain. Our results suggest that cyclooxygenase
      depending synthesis of fungal prostaglandins is important for morphogenesis and
      fungal virulence. Inhibitors of cyclooxygenase isoensymes (aspirin and
      diclofenac) are effective in decreasing germ tube formation of Candida albicans. 

PMID- 25763043
TI  - Candida species biofilm and Candida albicans ALS3 polymorphisms in clinical
      isolates.
AB  - Over the last decades, there have been important changes in the epidemiology of
      Candida infections. In recent years, Candida species have emerged as important
      causes of invasive infections mainly among immunocompromised patients. This study
      analyzed Candida spp. isolates and compared the frequency and biofilm production
      of different species among the different sources of isolation: blood, urine,
      vulvovaginal secretions and peritoneal dialysis fluid. Biofilm production was
      quantified in 327 Candida isolates obtained from patients attended at a Brazilian
      tertiary public hospital (Botucatu, Sao Paulo). C. albicans ALS3 gene
      polymorphism was also evaluated by determining the number of repeated motifs in
      the central domain. Of the 198 total biofilm-positive isolates, 72 and 126 were
      considered as low and high biofilm producers, respectively. Biofilm production by
      C. albicans was significantly lower than that by non-albicans isolates and was
      most frequently observed in C. tropicalis. Biofilm production was more frequent
      among bloodstream isolates than other clinical sources, in urine, the isolates
      displayed a peculiar distribution by presenting two distinct peaks, one
      containing biofilm-negative isolates and the other containing isolates with
      intense biofilm production. The numbers of tandem-repeat copies per allele were
      not associated with biofilm production, suggesting the evolvement of other
      genetic determinants. 

PMID- 25763045
TI  - Rapid detection of Salmonella Typhi by loop-mediated isothermal amplification
      (LAMP) method.
AB  - An in-house loop-mediated isothermal amplification (LAMP) reaction was
      established and evaluated for sensitivity and specificity in detecting the
      presence of Salmonella Typhi (S. Typhi) isolates from Kelantan, Malaysia. Three
      sets of primers consisting of two outer and 4 inner were designed based on locus
      STBHUCCB_38510 of chaperone PapD of S. Typhi genes. The reaction was optimised
      using genomic DNA of S. Typhi ATCC7251 as the template. The products were
      visualised directly by colour changes of the reaction. Positive results were
      indicated by green fluorescence and negative by orange colour. The test was
      further evaluated for specificity, sensitivity and application on field samples.
      The results were compared with those obtained by gold standard culture method and
      Polymerase Chain Reaction (PCR). This method was highly specific and -10 times
      more sensitive in detecting S. Typhi compared to the optimised conventional
      polymerase chain reaction (PCR) method. 

PMID- 25763046
TI  - Evaluation of antibacterial properties of Barium Zirconate Titanate (BZT)
      nanoparticle.
AB  - So far, the antibacterial activity of some organic and inorganic compounds has
      been studied. Barium zirconate titanate [Ba(ZrxTi1-x)O3] (x = 0.05) nanoparticle
      is an example of inorganic materials. In vitro studies have provided evidence for
      the antibacterial activity of this nanoparticle. In the current study, the nano
      powder was synthesized by sol-gel method. X-ray diffraction showed that the
      powder was single-phase and had a perovskite structure at the calcination
      temperature of 1000  degrees C. Antibacterial activity of the desired
      nanoparticle was assessed on two gram-positive (Staphylococcus aureus PTCC1431
      and Micrococcus luteus PTCC1625) and two gram-negative (Escherichia coli HP101BA
      7601c and clinically isolated Klebsiella pneumoniae) bacteria according to Radial
      Diffusion Assay (RDA). The results showed that the antibacterial activity of BZT
      nano-powder on both gram-positive and gram-negative bacteria was acceptable. The
      minimum inhibitory concentration of this nano-powder was determined. The results
      showed that MIC values for E. coli, K. pneumoniae, M. luteus and S. aureus were
      about 2.3 MUg/mL, 7.3 MUg/mL, 3 MUg/mL and 12 MUg/mL, respectively. Minimum
      bactericidal concentration (MBC) was also evaluated and showed that the growth of
      E. coli, K. pneumoniae, M. luteus and S. aureus could be decreased at 2.3, 14, 3
      and 18 MUg/mL of BZT. Average log reduction in viable bacteria count in time-kill
      assay ranged between 6 Log10 cfu/mL to zero after 24 h of incubation with BZT
      nanoparticle.

PMID- 25763047
TI  - Community-associated methicillin-resistant Staphylococcus aureus in non-outbreak
      skin infections.
AB  - The aim of this study was to determine the prevalence of Staphylococcus aureus
      and risk factors for the acquisition of MRSA (Methicillin Resistant
      Staphylococcus aureus) as the main cause of skin and soft tissue infections. S.
      aureus were characterized for the presence of PVL, TSST-1 and mecA genes. SCCmec
      typing was carried out in mecA positive strains and PFGE was performed only in
      these strains. During the study period, 127 outpatients attending a dermatology
      clinical the Botucatu Medical School, a regional tertiary hospital in Botucatu,
      Sao Paulo, Brazil, were diagnosed with active skin infections. A total 66 (56.9%)
      S. aureus strains were isolated. The methicillin resistance gene mecA was
      detected in seven (10.6%) S. aureus strains. The SCCmec types detected in the
      seven mecA-positive S. aureus strains were type Ia in one, type II in three, and
      type IV in three. The PVL gene was detected in 10 (15.1%) in sensitive strains.
      Pulsed field gel electrophoresis revealed non-clonal diversity among the
      isolates. The risk factors associated with MRSA acquisition in this study were
      previous ciprofloxacin use and working in a healthcare environment. The risk
      factors indicate plausible routes of CA-MRSA transmission among the subjects
      studied. 

PMID- 25763048
TI  - Antibacterial activity of alpha-terpineol may induce morphostructural alterations
      in Escherichia coli.
AB  - The antibacterial effect of alpha-terpineol from Cinnamomum longepaniculatum
      (Gamble) N. Chao leaf essential oils were studied with special reference to the
      mechanism of inhibiting the standard strain of Escherichia coli (CMCC (B) 44102)
      growth at ultrastructural level. Minimal inhibitory concentration (MIC) and
      minimal bactericidal concentration (MBC) and time-kill curves of alpha-terpineol
      were determined; Escherichia coli was treated with alpha-terpineol and observed
      under a transmission electron microscope. The MIC and MBC values of alpha
      terpineol were all 0.78 MUL/mL, and time-kill curves showed the concentration
      dependent. Under the transmission electron microscopy (TEM), Escherichia coli
      exposed to MIC levels of alpha-terpineol exhibited decreased cell size and
      irregular cell shape, cell wall and cell membrane were ruptured, nucleus
      cytoplasm was reduced and nuclear area gathered aside. Results suggest that alpha
      terpineol has excellent antibacterial activity and could induce morphological
      changes of Escherichia coli. 

PMID- 25763049
TI  - Procalcitonin and C-reactive protein in differantiating to contamination from
      bacteremia.
AB  - Procalcitonin (PCT) and C-reactive protein (CRP) are important biological markers
      used in the diagnosis of severe infections. The aim of this study was to evaluate
      the consistency of blood culture with PCT and CRP in differentiating
      contamination and non-bacteremia from true bacteremia. In this study blood
      samples were obtained from 809 febrile patients and analyzed using BACTEC 9120
      system. All of positive blood cultures were performed Gram staining. The
      microorganisms were identified with conventional methods and automated systems.
      Antibiotic susceptibility tests were made by disc diffusion. PCT levels were
      analyzed by mini VIDAS device and PCT kit. PCT and CRP levels were analyzed with
      blood cultures in same times. Kruskal Wallis test, Mann-Whitney U test,
      Spearman's rho test and ROC curve were used for statistical analyses. The
      bacteremia group was found to be significantly different from non-bacteremia
      group and contamination group in terms of both PCT and CRP (p<0.0001). The p
      values of PCT and CRP in differentiating bacteremia from non-bacteremia were
      p<0.001 for PCT, p=0.002 for CRP and in differentiating bacteremia from
      contamination were p<0.001 for PCT, p<0.001 for CRP. PCT is a more useful marker
      than CRP in the differentiating of true bacteremia from contamination according
      to the results of this study. 

PMID- 25763050
TI  - Proteus mirabilis biofilm - qualitative and quantitative colorimetric methods
      based evaluation.
AB  - Proteus mirabilis strains ability to form biofilm is a current topic of a number
      of research worldwide. In this study the biofilm formation of P. mirabilis
      strains derived from urine of the catheterized and non-catheterized patients has
      been investigated. A total number of 39 P. mirabilis strains isolated from the
      urine samples of the patients of dr Antoni Jurasz University Hospital No. 1 in
      Bydgoszcz clinics between 2011 and 2012 was used. Biofilm formation was evaluated
      using two independent quantitative and qualitative methods with TTC (2,3,5
      triphenyl-tetrazolium chloride) and CV (crystal violet) application. The obtained
      results confirmed biofilm formation by all the examined strains, except
      quantitative method with TTC, in which 7.7% of the strains did not have this
      ability. It was shown that P. mirabilis rods have the ability to form biofilm on
      the surfaces of both biomaterials applied, polystyrene and polyvinyl chloride
      (Nelaton catheters). The differences in ability to form biofilm observed between
      P. mirabilis strains derived from the urine of the catheterized and non
      catheterized patients were not statistically significant. 

PMID- 25763051
TI  - High seroprevalence of Simkania negevensis in Jordan.
AB  - The bacterium Simkania negevensis is a germ associated with respiratory diseases.
      This study aims at estimating the prevalence of Simkania in the Jordanian
      population. Serum samples from 664 Jordanian males and females, aged 2 to 86
      years were collected. IgG and IgM Simkania-specific antibodies were detected
      using an indirect immunofluorescence test. Seropositivity titers for IgG and IgM
      were defined as 1:8 and 1:10, respectively. The overall prevalence of IgG
      antibody in all examined Jordanian nationals was 58.4%. IgG seropositivity was
      low in children under the age of 10 years (34.2%), and increased rapidly with age
      and ranged between 49.4% and 72%. Simkania-specific IgM was detected in 24.8% of
      subjects. IgM prevalence in children under 10 years was lowest (10.5%) and
      increased in older ages and remained above 20%. Overall detection rates of both
      IgG and IgM were significantly higher in females than males (60.7% vs. 54.5% for
      IgG and 26.7% vs. 21.7% for IgM). These data indicate that Simkania infection is
      highly prevalent in Jordan. The high level of seropositivity is most likely
      maintained by re-infections or chronic infections. Our data may serve as a basis
      to elucidate the pathogenesis of Simkania in Jordan. 

PMID- 25763052
TI  - Antimicrobial susceptibility testing for Helicobacter pylori isolates from
      Brazilian children and adolescents: comparing agar dilution, E-test, and disk
      diffusion.
AB  - Antimicrobial susceptibility testing for Helicobacter pylori is increasingly
      important due to resistance to the most used antimicrobials agents. Only agar
      dilution method is approved by CLSI, but it is difficult to perform routinely. We
      evaluated the reliability of E-test and disk diffusion comparing to agar dilution
      method on Helicobacter pylori antimicrobial susceptibility testing.
      Susceptibility testing was performed for amoxicillin, clarithromycin,
      furazolidone, metronidazole and tetracycline using E-test, disk-diffusion and
      agar dilution method in 77 consecutive Helicobacter pylori strains from dyspeptic
      children and adolescents. Resistance rates were: amoxicillin - 10.4%, 9% and
      68.8%; clarithromycin - 19.5%, 20.8%, 36.3%; metronidazole - 40.2%33.7%, 38.9%,
      respectively by agar dilution, E-test and disk diffusion method. Furazolidone and
      tetracycline showed no resistance rates. Metronidazole presented strong
      correlation to E-test (r = 0.7992, p < 0.0001) and disk diffusion method (r=
      0.6962, p < 0.0001). Clarithromycin presented moderate correlation to E-test (r =
      0.6369, p < 0.0001) and disk diffusion method (r=-0.5656, p < 0.0001).
      Amoxicillin presented weak correlation to E-test (r = 0.3565, p = 0.0015) and
      disk diffusion (r=-0.3565, p = 0.0015). Tetracycline presented weak correlation
      with E-test (r = 0.2346, p = 0.04) and furazolidone to disk diffusion (r=-0.0288,
      p = 0.8038). E-test presented better agreement with gold standard. It is an easy
      and reliable method for Helicobacter pylori susceptibility testing. Disk
      diffusion method presented high disagreement and high rates of major errors. 

PMID- 25763053
TI  - Inflammatory response of Haemophilus influenzae biotype aegyptius causing
      Brazilian Purpuric Fever.
AB  - The Brazilian Purpuric Fever (BPF) is a systemic disease with many clinical
      features of meningococcal sepsis and is usually preceded by purulent
      conjunctivitis. The illness is caused by Haemophilus influenza biogroup
      aegyptius, which was associated exclusively with conjunctivitis. In this work
      construction of the las gene, hypothetically responsible for this virulence, were
      fusioned with ermAM cassette in Neisseria meningitidis virulent strains and had
      its DNA transfer to non BPF H. influenzae strains. The effect of the las transfer
      was capable to increase the cytokines TNFalpha and IL10 expression in Hec-1B
      cells line infected with these transformed mutants (in eight log scale of folding
      change RNA expression). This is the first molecular study involving the las
      transfer to search an elucidation of the pathogenic factors by horizontal
      intergeneric transfer from meningococci to H. influenzae. 

PMID- 25763054
TI  - Prevalence of resistance to aminoglycosides and fluoroquinolones among
      Pseudomonas aeruginosa strains in a University Hospital in Northeastern Poland.
AB  - The present study was conducted to investigate the prevalence of genes encoding
      resistance to aminoglycosides and fluoroquinolones among twenty-five Pseudomonas
      aeruginosa isolated between 2002 and 2009. In PCR, following genes were detected:
      ant(2")-Ia in 9 (36.0%), aac(6')-Ib in 7 (28.0%), qnrB in 5 (20.0%), aph(3")-Ib
      in 2 (8.0%) of isolates. 

PMID- 25763055
TI  - Screening of thermotolerant and thermophilic fungi aiming beta-xylosidase and
      arabinanase production.
AB  - Plant cell wall is mainly composed by cellulose, hemicellulose and lignin. The
      heterogeneous structure and composition of the hemicellulose are key impediments
      to its depolymerization and subsequent use in fermentation processes. Thus, this
      study aimed to perform a screening of thermophilic and thermotolerant filamentous
      fungi collected from different regions of the Sao Paulo state, and analyze the
      production of beta-xylosidase and arabinanase at different temperatures. These
      enzymes are important to cell wall degradation and synthesis of end products as
      xylose and arabinose, respectively, which are significant sugars to fermentation
      and ethanol production. A total of 12 fungal species were analyzed and 9 of them
      grew at 45  degrees C, suggesting a thermophilic or thermotolerant character.
      Additionally Aspergillus thermomutatus anamorph of Neosartorya and A. parasiticus
      grew at 50  degrees C. Aspergillus niger and Aspergillus thermomutatus were the
      filamentous fungi with the most expressive production of beta-xylosidase and
      arabinanase, respectively. In general for most of the tested microorganisms, beta
      xylosidase and arabinanase activities from mycelial extract (intracellular form)
      were higher in cultures grown at high temperatures (35-40  degrees C), while the
      correspondent extracellular activities were favorably secreted from cultures at
      30  degrees C. This study contributes to catalogue isolated fungi of the state of
      Sao Paulo, and these findings could be promising sources for thermophilic and
      thermotolerant microorganisms, which are industrially important due to their
      enzymes. 

PMID- 25763056
TI  - New cultive medium for bioconversion of C5 fraction from sugarcane bagasse using
      rice bran extract.
AB  - The use of hemicellulosic hydrolysates in bioprocesses requires supplementation
      as to ensure the best fermentative performance of microorganisms. However, in
      light of conflicting data in the literature, it is necessary to establish an
      inexpensive and applicable medium for the development of bioprocesses. This paper
      evaluates the fermentative performance of Scheffersomyces (Pichia) stipitis and
      Candida guilliermondii growth in sugarcane bagasse hemicellulosic hydrolysate
      supplemented with different nitrogen sources including rice bran extract, an
      important by-product of agroindustry and source of vitamins and amino acids.
      Experiments were carried out with hydrolysate supplemented with rice bran extract
      and (NH4)2SO4; peptone and yeast extract; (NH4)2SO4, peptone and yeast extract
      and non-supplemented hydrolysate as a control. S. stipitis produced only ethanol,
      while C. guilliermondii produced xylitol as the main product and ethanol as by
      product. Maximum ethanol production by S. stipitis was observed when sugarcane
      bagasse hemicellulosic hydrolysate was supplemented with (NH4)2SO4, peptone and
      yeast extract. Differently, the maximum xylitol formation by C. guilliermondii
      was obtained by employing hydrolysate supplemented with (NH4)2SO4 and rice bran
      extract. Together, these findings indicate that: a) for both yeasts (NH4)2SO4 was
      required as an inorganic nitrogen source to supplement sugarcane bagasse
      hydrolysate; b) for S. stipitis, sugarcane hemicellulosic hydrolysate must be
      supplemented with peptone and yeast extract as organic nitrogen source; and: c)
      for C. guilliermondii, it must be supplemented with rice bran extract. The
      present study designed a fermentation medium employing hemicellulosic hydrolysate
      and provides a basis for studies about value-added products as ethanol and
      xylitol from lignocellulosic materials.

PMID- 25763057
TI  - Reducing lactate secretion by ldhA Deletion in L-glutamate- producing strain
      Corynebacterium glutamicum GDK-9.
AB  - L-lactate is one of main byproducts excreted in to the fermentation medium. To
      improve L-glutamate production and reduce L-lactate accumulation, L-lactate
      dehydrogenase-encoding gene ldhA was knocked out from L-glutamate producing
      strain Corynebacterium glutamicum GDK-9, designated GDK-9DeltaldhA. GDK
      9DeltaldhA produced approximately 10.1% more L-glutamate than the GDK-9, and
      yielded lower levels of such by-products as alpha-ketoglutarate, L-lactate and L
      alanine. Since dissolved oxygen (DO) is one of main factors affecting L-lactate
      formation during L-glutamate fermentation, we investigated the effect of ldhA
      deletion from GDK-9 under different DO conditions. Under both oxygen-deficient
      and high oxygen conditions, L-glutamate production by GDK-9DeltaldhA was not
      higher than that of the GDK-9. However, under micro-aerobic conditions, GDK
      9DeltaldhA exhibited 11.61% higher L-glutamate and 58.50% lower L-alanine
      production than GDK-9. Taken together, it is demonstrated that deletion of ldhA
      can enhance L-glutamate production and lower the unwanted by-products
      concentration, especially under micro-aerobic conditions. 

PMID- 25763058
TI  - Production of plant cell wall degrading enzymes by monoculture and co-culture of
      Aspergillus niger and Aspergillus terreus under SSF of banana peels.
AB  - Filamentous fungi are considered to be the most important group of microorganisms
      for the production of plant cell wall degrading enzymes (CWDE), in solid state
      fermentations. In this study, two fungal strains Aspergillus niger MS23 and
      Aspergillus terreus MS105 were screened for plant CWDE such as amylase,
      pectinase, xylanase and cellulases (beta-glucosidase, endoglucanase and
      filterpaperase) using a novel substrate, Banana Peels (BP) for SSF process. This
      is the first study, to the best of our knowledge, to use BP as SSF substrate for
      plant CWDE production by co-culture of fungal strains. The titers of pectinase
      were significantly improved in co-culture compared to mono-culture. Furthermore,
      the enzyme preparations obtained from monoculture and co-culture were used to
      study the hydrolysis of BP along with some crude and purified substrates. It was
      observed that the enzymatic hydrolysis of different crude and purified substrates
      accomplished after 26 h of incubation, where pectin was maximally hydrolyzed by
      the enzyme preparations of mono and co-culture. Along with purified substrates,
      crude materials were also proved to be efficiently degraded by the cocktail of
      the CWDE. These results demonstrated that banana peels may be a potential
      substrate in solid-state fermentation for the production of plant cell wall
      degrading enzymes to be used for improving various biotechnological and
      industrial processes. 

PMID- 25763059
TI  - Microbial mediated preparation, characterization and optimization of gold
      nanoparticles.
AB  - The need for eco-friendly and cost effective methods for nanoparticles synthesis
      is developing interest in biological approaches which are free from the use of
      toxic chemicals as byproducts. This study aimed to biosynthesize and optimize the
      size of gold nanoparticles which produced by biotechnological method using
      Penicillium crustosum isolated from soil. Initially, Penicillium crustosum was
      grown in fluid czapek dox broth on shaker at 28  degrees C and 200 rpm for ten
      days and then the supernatant was separated from the mycelia to convert AuCl4
      solution into gold nanoparticles. The synthesized nanoparticles in the optimum
      conditions were formed with fairly well-defined dimensions and good
      monodispersity. The characterizations were done by using different methods (UV
      Visible Spectroscopy, Fluorescence, FT-IR, AFM (Atomic Force Microscopy) and DLS
      (Dynamic Light Scattering). The bioconversion was optimized by Box-Behnken
      experimental design. The results show that the effective factors in this process
      were concentration of AuCl4, pH of medium and temperature of shaker incubator.
      The R(2) value was calculated to be 0.9999 indicating the accuracy and ability of
      the polynomial model. It can be concluded that the use of multivariate analysis
      facilitated to find out the optimum conditions for the biosynthesis of gold
      nanoparticles induced by Penicillium crustosum in a time and cost effective
      process. The current approach suggested that rapid synthesis of gold
      nanoparticles would be suitable for developing a biological process for mass
      scale production of formulations.

PMID- 25763060
TI  - Production and characterization of an extracellular lipase from Candida
      guilliermondii.
AB  - Extracellular lipases from the endophytic yeast Candida guilliermondii isolated
      from castor leaves (Ricinus communis L.) were produced using low-cost raw
      materials such as agro-industrial residues and applying them in the
      esterification of oleic acid for evaluating their potential use in biodiesel
      production. After partial purification using ammonium sulfate, the enzyme was
      characterized and presented higher activity (26.8 +/- 1.5 U mL(-1)) in the
      presence of 5 mmol L(-1) NaCl at 30  degrees C and pH 6.5. The production through
      submerged fermentation was formerly performed in 150 mL erlenmeyer flasks and,
      once the enzyme production was verified, assays in a 14 L bioreactor were
      conducted, obtaining 18 +/- 1.4 U mL(-1). The produced enzyme was applied in the
      oleic acid esterification under different solvents: hexane, cyclohexane or
      cyclohexanone) and different acid:alcohol molar ratios. Higher ester conversion
      rate (81%) was obtained using hexane and the molar ratio of 1:9 was the best
      conditions using methanol. The results suggest the potential for development of
      endophytic yeast in the production of biocatalyst through submerged fermentation
      using agroindustrial residues as culture medium. 

PMID- 25763061
TI  - Experimental infection of BHK21 and Vero cell lines with different Mycoplasma
      spp.
AB  - Mycoplasma spp, belongs to the class Mollicutes and is capable to produce
      alterations in cellular cultures causing damages to the biotechnological
      industry. Bioproducts generally require two essential inputs, bovine serum and
      cells. The study herein aims to evaluate the mycoplasma concentrations that
      affect the growing of BHK21 and Vero cells. The species used were: Mycoplasma
      orale, M. salivarium, M. arginini and M. hyorhinis, cultivated in a SP4 media.
      Two contamination tests were performed with BHK21 and Vero cells and one of them
      applied different concentrations of mycoplasma. In the first one, mycoplasma was
      applied at the day zero and, in the second one, the contamination was performed
      after the monolayer establishment. The both cellular cultures presented
      cytopathic effects with mycoplasma contamination, but the Vero cells suffered
      more damages than the BHK21 ones. It was also observed that the severity of the
      cytopathic effect depended on the mycoplasma specie, on the concentration and on
      the time of contact with the cellular culture, which evidences the importance of
      controlling the presence of mycoplasma in biotechnological industries. 

PMID- 25763062
TI  - Immune response elicited by the oral administration of an intermediate strain of
      IBDV in chickens.
AB  - The immune response elicited by the oral inoculation of an intermediate strain of
      infectious bursal disease virus was studied in chickens. A strong over expression
      of IL-6, IL-8, IFNalpha and IFNgamma was observed in bursa at 3 days post
      inoculation together with an increase in splenic NO2 release. An influx of T
      lymphocytes was also detected. 

PMID- 25763063
TI  - Molecular characterization of the first leptospires isolated from goats in
      Brazil.
AB  - Two Leptospira sp. isolates were obtained by the first time from goats in Brazil
      and characterized by sequencing rrs, rpoB and secY genes, PFGE and typing with
      monoclonal antibodies. Both isolates are identical and belong to Leptospira
      santarosai. Analysis of the rrs and the rpoB genes sequences revealed 100%
      identity between the goat isolates and the Bananal reference strain. When secY
      sequences of the two isolates were compared to each other, it was observed that
      they had identical sequences. However, when compared to that of the Bananal
      reference strain, there were 15 mismatches along the 549 bp secY sequence. In
      conclusion, molecular methods are increasingly useful for the characterization of
      leptospires and allowed to identify those isolates of caprine origin as closely
      related but not identical to serovar Bananal, and constitute a new type named
      Carioca. 

PMID- 25763064
TI  - Nasal, oral and rectal microbiota of Black lion tamarins (Leontopithecus
      chrysopygus).
AB  - Black lion tamarins (Leontopithecus chrysopygus) are endangered callithrichids.
      Their conservation may require future translocations or reintroductions; however
      these approaches involve risks of pathogen introduction in the environment and
      stress-related opportunistic infections in these animals. In order to screen for
      opportunistic and potential pathogenic bacterial and fungal microbiota, ten free
      ranging and ten captive Black lion tamarins were studied and the results
      compared. Nasal, oral and rectal swabs were collected and cultured for aerobic
      and facultative anaerobic bacteria and fungi, and a total 203 bacterial and 84
      fungal isolates were obtained. Overall, the most frequent organisms were
      Staphylococcus spp., Bacillus spp., Candida spp. and Aspergillus spp. Microbiota
      of free-ranging and captive animals were similar in composition. A number of
      potentially pathogenic organisms were identified, emphasizing the importance of
      microbiological screening in future translocation or reintroduction conservation
      management programs. 

PMID- 25763066
TI  - Detection of thermophilic Campylobacter sp. in raw chicken sausages by methods
      ISO 10272: 2006 in Curitiba - Parana State - Brazil.
AB  - The aim of this study was the detection of Campylobacter sp. in raw chicken
      sausages using the methods ISO 10272-1 and ISO 10272-2. The overall prevalence of
      Campylobacter sp. in the samples tested was 16.67%, representing a serious risk
      to the health of consumers, particularly if measures guaranteeing proper cooking
      of foods and prevention of cross-contamination are not adopted. Furthermore, the
      majority of campylobacteriosis cases in humans are caused by consumption or
      improper handling of contaminated raw or undercooked poultry meat, which
      constitute the main vehicle of this infection. 

PMID- 25763065
TI  - Bacteriocinogenic Lactococcus lactis subsp. lactis DF04Mi isolated from goat
      milk: characterization of the bacteriocin.
AB  - Lactic acid bacteria capable of producing bacteriocins and presenting probiotic
      potential open innovative technological applications in the dairy industry. In
      this study, a bacteriocinogenic strain (Lactococcus lactis subsp. lactis DF4Mi)
      was isolated from goat milk, and studied for its antimicrobial activity. The
      bacteriocin presented a broad spectrum of activity, was sensitive to proteolytic
      enzymes, resistant to heat and pH extremes, and not affected by the presence of
      SDS, Tween 20, Tween 80, EDTA or NaCl. Bacteriocin production was dependent on
      the components of the culture media, especially nitrogen source and salts. When
      tested by PCR, the bacteriocin gene presented 100% homology to nisin Z gene.
      These properties indicate that this L. lactis subsp. lactis DF4Mi can be used for
      enhancement of dairy foods safety and quality. 

PMID- 25763067
TI  - Efficient assembly of full-length infectious clone of Brazilian IBDV isolate by
      homologous recombination in yeast.
AB  - The Infectious Bursal Disease Virus (IBDV) causes immunosuppression in young
      chickens. Advances in molecular virology and vaccines for IBDV have been achieved
      by viral reverse genetics (VRG). VRG for IBDV has undergone changes over time,
      however all strategies used to generate particles of IBDV involves multiple
      rounds of amplification and need of in vitro ligation and restriction sites. The
      aim of this research was to build the world's first VRG for IBDV by yeast-based
      homologous recombination; a more efficient, robust and simple process than
      cloning by in vitro ligation. The wild type IBDV (Wt-IBDV-Br) was isolated in
      Brazil and had its genome cloned in pJG-CMV-HDR vector by yeast-based homologous
      recombination. The clones were transfected into chicken embryo fibroblasts and
      the recovered virus (IC-IBDV-Br) showed genetic stability and similar phenotype
      to Wt-IBDV-Br, which were observed by nucleotide sequence, focus size/morphology
      and replication kinetics, respectively. Thus, IBDV reverse genetics by yeast
      based homologous recombination provides tools to IBDV understanding and
      vaccines/viral vectors development. 

PMID- 25763069
TI  - Corrigendum to "Quality of Life and Sexual Health in the Aging of PCa Survivors".
AB  - [This corrects the article DOI: 10.1155/2014/470592.]. 

PMID- 25763068
TI  - Biodegradation of [D-Leu(1)] microcystin-LR by a bacterium isolated from sediment
      of Patos Lagoon estuary, Brazil.
AB  - BACKGROUND: Toxic cyanobacterial blooms are recurrent in Patos Lagoon, in
      southern Brazil. Among cyanotoxins, [D-Leu(1)] microcystin-LR is the predominant
      variant whose natural cycle involves water and sediment compartments. This study
      aimed to identify and isolate from sediment a bacterial strain capable of growing
      on [D-Leu(1)] microcystin-LR. Sediment and water samples were collected at two
      distinct aquatic spots: close to the Oceanographic Museum (P1), in Rio Grande
      City, and on Sao Lourenco Beach (P2), in Sao Lourenco do Sul City, southern
      Brazil. METHODS: [D-Leu(1)] microcystin-LR was isolated and purified from batch
      cultures of Microcystis aeruginosa strain RST9501. Samples of water and sediment
      from Rio Grande and Sao Lourenco do Sul were collected. Bacteria from the samples
      were allowed to grow in flasks containing solely [D-Leu(1)] microcystin-LR. This
      strain named DMSX was isolated on agar MSM with 8 g L(-1) glucose and further
      purified on a cyanotoxin basis growth. Microcystin concentration was obtained by
      using the ELISA immunoassay for microcystins whereas bacterial count was
      performed by epifluorescence microscopy. The genus Pseudomonas was identified by
      DNA techniques. RESULTS: Although several bacterial strains were isolated from
      the samples, only one, DMXS, was capable of growing on [D-Leu(1)] microcystin-LR.
      The phylogenetic analysis of the 16S rRNA gene from DMXS strain classified the
      organism as Pseudomonas aeruginosa. DMXS strain incubated with [D-Leu(1)]
      microcystin-LR lowered the amount of toxin from 1 MUg.L(-1) to < 0.05 MUg.L(-1).
      Besides, an increase in the bacterial count-from 71 * 10(5) bacteria.mL(-1) to
      117 * 10(5) bacteria.mL(-1)-was observed along the incubation. CONCLUSIONS: The
      use of bacteria isolated from sediment for technological applications to remove
      toxic compounds is viable. Studies have shown that sediment plays an important
      role as a source of bacteria capable of degrading cyanobacterial toxins. This is
      the first Brazilian report on a bacterium-of the genus Pseudomonas-that can
      degrade [D-Leu(1)] microcystin-LR, the most frequent microcystin variant in
      Brazilian freshwaters.

PMID- 25763070
TI  - Vomiting-induced gastric emphysema and hepatoportal venous gas: a case report and
      review of the literature.
AB  - Gastric pneumatosis is the presence of air within the wall of the stomach. It
      represents a spectrum of conditions ranging from benign disease to septic shock
      and death. Etiopathologically, it can be classified into emphysematous gastritis
      or gastric emphysema (GE). Along with hepatoportal venous gas (HPVG), it was
      considered as an ominous radiological sign and warranted an emergent surgical
      exploration; however, with widespread use of computerized tomographic (CT) scan,
      an increasing number of benign causes of GE and HPVG have been reported in the
      literature, where patients can be managed by noninvasive and conservative
      measures. We hereby describe a case where recurrent episodes of vomiting led to
      development of GE and HPVG and the patient was managed successfully by
      conservative measures. 

PMID- 25763071
TI  - Common atrium: a rare cause of acute decompensated heart failure.
AB  - We report a rare case of common atrium and acute decompensated heart failure most
      likely precipitated by acute bacterial pericarditis leading to premature death,
      in a 25-year-old male footballer. The silent course of the disease for decades as
      well as the diagnostic and management pitfalls of this case illustrates the
      importance of early detection by echocardiography and urgent appropriate
      treatment in intensive care settings to limit the poor prognosis of the
      condition. 

PMID- 25763073
TI  - Percutaneous transarterial embolization of spontaneously ruptured ovarian artery
      aneurysm using N-butyl cyanoacrylate.
AB  - A 52-year-old post-menopausal female was admitted to the emergency room due to
      acute onset of abdominal pain in the right lower quadrant. There was no history
      of trauma of the abdomen. Contrast-enhanced multi-detector computed tomography
      (MDCT) of the abdomen and pelvis revealed a massive right retroperitoneal
      hematoma and contrast extravasation from a right ovarian artery aneurysm. Digital
      subtraction angiography showed an active bleeding from a right ovarian artery
      aneurysm, which was embolized successfully, using n-butyl-cyanoacrylate. 

PMID- 25763074
TI  - Does magnetic resonance imaging affect the microleakage of amalgam restorations?
AB  - BACKGROUND: The effect of MRI on microleakage of amalgam restorations is an
      important health issue that should be considered. If MRI application causes
      increase of microleakage, amalgam fillings should be reassessed after MRI and
      replaced if necessary. OBJECTIVES: The aim of this study is to compare the effect
      of magnetic resonance imaging (MRI) on microleakage of class II bonded amalgam
      versus classical amalgam restorations. MATERIALS AND METHODS: Class II cavities
      (3 mm width * 1.5 mm depth) with gingival margins ending 1 mm below the
      cementoenamel junction (CEJ) were prepared in 40 permanent molar teeth. The teeth
      were randomly divided into four groups. Cavities in the first and second groups
      were restored with dentin adhesive and amalgam (bonded amalgam), and those in the
      third and fourth groups with amalgam only. MRI was performed with the teeth
      specimens from the first and third groups. All specimens were then thermocycled
      at 5 degrees  to 55 degrees  C with a 30-second dwell time for 1000 cycles. The
      samples were then immersed in 0.5% methylene blue dye for 24 hours and sectioned
      longitudinally. Dye penetration at the occlusal and gingival margins was
      quantified by 15* stereomicroscopy. IBM SPSS Statistics ver. 21.0 (IBM Corp.,
      Released 2012., IBM SPSS Statistics for Windows, Armonk, NY: IBM Corp.) and MS
      Excel 2007 programs were used for statistical analyses and calculations. "nparLD"
      module was used for F2_LD_F1 design analysis at R program. P<0.05 was considered
      statistically significant. RESULTS: In teeth with amalgam filling, there were no
      significant differences of occlusal and gingival surface microleakage after MRI
      exposure. Occlusal and gingival surface microleakages were also similar with and
      without MRI in teeth with bonded amalgam filling. CONCLUSIONS: The results of
      this study suggest that MRI does not increase microleakage of amalgam
      restorations.

PMID- 25763075
TI  - Primary pulmonary lymphoma and cutaneous metastasis: a case report.
AB  - Diffuse large B cell lymphoma is the most common type of non-Hodgkin's lymphoma,
      representing nearly one-third of all cases. Any organ can be involved, making a
      diagnostic biopsy imperative. When the lungs are the involved organs, it is
      called primary pulmonary lymphoma (PPL). Hereby, we present a case of PPL that
      demonstrated a single large mass on chest CT and had metastatic skin lesions. The
      diagnosis of PPL was performed by histopathology and immunohistochemistry
      staining of the transthoracic lung biopsy and skin lesion specimens. This case
      highlighted an unusual and subtle clinical presentation, and the importance of
      new onset pulmonary symptoms and a large lung mass on chest X-ray. Review of the
      literature on the patient's radiographic presentation revealed various findings,
      the most common of which were single or multiple nodular lesions in one or two
      lungs. It highlighted the fact that this diagnosis should be considered in all
      cases with a lung mass and skin lesions. 

PMID- 25763072
TI  - Satellite cells: regenerative mechanisms and applicability in muscular dystrophy.
AB  - The satellite cells are long regarded as heterogeneous cell population, which is
      intimately linked to the processes of muscular recovery. The heterogeneous cell
      population may be classified by specific markers. In spite of the significant
      amount of variation amongst the satellite cell populations, it seems that their
      activity is tightly bound to the paired box 7 transcription factor expression,
      which is, therefore, used as a canonical marker for these cells. Muscular
      dystrophic diseases, such as Duchenne muscular dystrophy, elicit severe tissue
      injuries leading those patients to display a very specific pattern of muscular
      recovery abnormalities. There have been works on the application of precursors
      cells as a therapeutic alternative for Duchenne muscular dystrophy and initial
      attempts have proven the cells inefficient; however later endeavours have
      proposed solutions for the experiments improving significantly the results. The
      presence of a range of satellite cells populations indicates the existence of
      specific cells with enhanced capability of muscular recovery in afflicted
      muscles. 

PMID- 25763076
TI  - Outcome of retinoblastoma following limited sessions of intra-arterial
      chemotherapy in iran.
AB  - BACKGROUND: The management of retinoblastoma remains a challenge to the
      multidisciplinary team, particularly as treatment affects not only visual
      outcomes, but also ocular retention and morbidity. Management of retinoblastoma
      has evolved over the past two decades. OBJECTIVES: To report the result of intra
      ophthalmic artery chemotherapy (IAC) for the treatment of refractory and advanced
      retinoblastoma tumors. PATIENTS AND METHODS: All patients who had failed to
      respond adequately to previous treatments and six naive patients with advanced
      retinoblastoma, receiving IAC between 2009 and 2012, were included in this
      institutional interventional case series. The patients received 1-2 treatments of
      IAC given 4-8 weeks apart. Complete response was defined as regressed tumor and
      complete disappearance of seeding clinically and partial response was defined as
      partial regression of the tumor with live parts of the tumor and/or lessening of
      seeds, but not complete disappearance of them clinically. RESULTS: A total of 24
      eyes of 24 patients were treated with IAC during the study period. The mean age
      at the time of IAC was 38.9 months (14-120 months), and the mean follow-up was
      16.8 months (3-36 months) after IAC. Tumor control was achieved in 14 eyes
      (58.3%). Type 3 (combined fleshy and calcified remnants) was the most common type
      of regression (37.5%). Complications included vitreous hemorrhage in nine eyes
      (37.5%), arterial occlusion in two (8.3%), cyclitic membrane possibly secondary
      to ischemia and tractional retinal detachment in one patient (4.2%),
      chorioretinal atrophy in three (12.5%) patients, and neovascular glaucoma in one
      eye (4.2%). In eight (33.3%) patients, no complication happened. Globe salvage
      was achieved in 62.5% of the cases. The success rate for naive patients was 84%.
      Sixty-seven percent of the cases received transpupillary thermotherapy and
      cryotherapy before IAC. CONCLUSIONS: Intra-ophthalmic artery melphalan is an
      effective treatment for advanced cases of retinoblastoma, with a reasonable level
      of success. In the short follow up period of this study, it appears that the
      primary cases showed better results in the control of tumor.

PMID- 25763077
TI  - Safety and Efficacy of Percutaneous CT-Guided Drainage in the Management of
      Abdominopelvic Abscess.
AB  - BACKGROUND: Abdominopelvic fluid collection and abscess management and their
      outcomes have improved in the recent years due to innovation of the image-guided
      drainage technique and improvement of surgical procedures. OBJECTIVES: This study
      was undertaken to evaluate the efficacy of CT-guided percutaneous drainage in
      treating abdominopelvic abscesses. PATIENTS AND METHODS: In this study, the data
      of 41 patients who had abdominal abscess or fluid collections, and underwent
      treatment by percutaneous CT-guided drainage were analyzed. Treatment was
      assessed by reduction of collection size, relief of symptoms and signs including
      abdominal pain and fever and imaging findings. Any morbidity such as wound
      infection, sepsis, hematoma formation or peritonitis was followed up to six
      months after the procedure. RESULTS: The average age of the patients was 54 years
      (range 12 to 79), including 21 (51%) men and 20 (49%) women. The common signs and
      symptoms were pain (83%) and fever (80.5%). The most prevalent abdominal abscess
      etiology was previous surgery in 31 cases (75.5%). Abscess diameter ranged
      between 5 and 12 cm (mean, 7.8 cm). The average hospital stay was 8 days (4-15).
      Thirty five cases (86%) were successfully treated. Only one case (2.5%) developed
      complication (peritonitis) after the procedure. CONCLUSIONS: According to our
      findings, CT-guided percutaneous drainage is a safe and effective procedure in
      the treatment of abdominal abscess and fluid collection.

PMID- 25763078
TI  - Reliability of rehabilitative ultrasonography to measure transverse abdominis and
      multifidus muscle dimensions.
AB  - BACKGROUND: Lumbar paraspinal muscles play an important role in providing both
      mobility and stability during dynamic tasks. Among paraspinal muscles, transverse
      abdominis and lumbar multifidus have been of particular interest as active
      stabilizers of the lumbar spine. These muscles may become dysfunctional in
      chronic low back pain (CLBP). Low back injury can result in muscle inhibition and
      control loss that cannot recover spontaneously, and specific exercises are
      required to stimulate their recovery. OBJECTIVES: The purpose of this study was
      to test the reliability of ultrasonography to measure muscle dimensions and to
      present a reliable method for measuring transverse abdominis and lumbar
      multifidus as stabilizing muscles of the lumbar spine. SUBJECTS AND METHODS:
      Fifteen healthy participants (18-55 year olds) were evaluated by a radiologist
      using ultrasonography (ES500) with two probes (50mm linear 7.5 MHZ and 70 mm
      curvilinear 3.5 MHz). The muscle thickness of transverse abdominis and the
      anterior-posterior diameter and cross sectional area of the LMF were measured. To
      determine within and between days reliabilities, second and third measurements
      were repeated with half an hour and one week intervals, respectively. RESULTS:
      Intraclass correlation coefficient for left and right showed good to high
      reliability for the cross sectional area of lumbar multifidi (0.74 and 0.88,
      respectively) as well as the anterior-posterior dimensions of lumbar multifidi
      (0.89 and 0.91, respectively) and transverse abdomini thickness (0.73 and 0.85,
      respectively). CONCLUSIONS: Rehabilitative ultrasonography is a reliable and non
      invasive instrument to measure muscle thickness. The method used in this study is
      a reliable way to measure lumbar stabilizing muscles.

PMID- 25763079
TI  - Diagnostic accuracy of secondary ultrasound exam in blunt abdominal trauma.
AB  - BACKGROUND: In stable patients with blunt abdominal trauma, accurate diagnosis of
      visceral injuries is crucial. OBJECTIVES: To determine whether repeating
      ultrasound exam will increase the sensitivity of focused abdominal sonography for
      trauma (FAST) through revealing additional free intraperitoneal fluid in patients
      with blunt abdominal trauma. PATIENTS AND METHODS: We performed a prospective
      observational study by performing primary and secondary ultrasound exams in blunt
      abdominal trauma patients. All ultrasound exams were performed by four radiology
      residents who had the experience of more than 400 FAST exams. Five routine
      intraperitoneal spaces as well as the interloop space were examined by ultrasound
      in order to find free fluid. All patients who expired or were transferred to the
      operating room before the second exam were excluded from the study. All positive
      ultrasound results were compared with intra-operative and computed tomography
      (CT) findings and/or the clinical status of the patients. RESULTS: Primary
      ultrasound was performed in 372 patients; 61 of them did not undergo secondary
      ultrasound exam; thus, were excluded from the study.Three hundred eleven patients
      underwent both primary and secondary ultrasound exams. One hundred and two of all
      patients were evaluated by contrast enhanced CT scan and 31 underwent laparotomy.
      The sensitivity of ultrasound exam in detecting intraperitoneal fluid
      significantly increased from 70.7% for the primary exam to 92.7% for the
      secondary exam. Examining the interloop space significantly improved the
      sensitivity of ultrasonography in both primary (from 36.6% to 70.7%) and
      secondary (from 65.9% to 92.7%) exams. CONCLUSIONS: Performing a secondary
      ultrasound exam in stable blunt abdominal trauma patients and adding interloop
      space scan to the routine FAST exam significantly increases the sensitivity of
      ultrasound in detecting intraperitoneal free fluid.

PMID- 25763080
TI  - Laryngeal paraganglioma: a case report.
AB  - Paragangliomas in the head and neck are found typically in the region of the
      carotid body, jugular body, and along the 9th and 10th cranial nerves. They can
      occur in multicenteric forms, but generally, laryngeal paragangliomas are not
      found in these patients. Only two cases of laryngeal paraganglioma have been
      reported with a synchronous lesion elsewhere. We report an additional case of a
      34-year-old female with multiple paragangliomas beginning with laryngeal
      involvement. 

PMID- 25763081
TI  - Computed tomography findings of a patient with severe dysplasia of the inner ear
      and recurrent meningitis: a case report of gusher ear in a five-year old boy.
AB  - Communication between subarachnoid and perlymphatic spaces can be due to a
      deficiency of lamina cribrosa (stapes gusher). Recognition of the condition may
      alter the course of treatment that can avoid perilymph gushing. A five-year-old
      boy presented with a history of congenital hearing loss and recurrent meningitis.
      The computed tomography (CT) of the temporal bone showed severe bilateral
      dysplasia in the inner ears in favor of gusher disease. 

PMID- 25763082
TI  - Lipomatosis of terminal ileum and ileocecal valve: multidetector computed
      tomography findings.
AB  - Intestinal lipomatosis also known as lipohyperplasia is a rare disease. Diffuse
      infiltration of the fatty tissue mainly in the submucosal layer is
      characteristic. It is usually asymptomatic and found incidentally. We report a
      case of lipomatosis in the terminal ileum and ileocecal valve. Multidetector
      computed tomography (MDCT) with contrast enhancement showed fatty infiltration of
      the terminal ileum and ileocecal valve. 

PMID- 25763083
TI  - Unsuspected pregnancy during hysterosalpingography.

PMID- 25763084
TI  - Treatment of a Bilateral Sacral Insufficiency Fracture with CT-Guided Balloon
      Sacroplasty.
AB  - Fractures of the os sacrum can be the cause of severe pain and immobility. A
      common cause of insufficiency fractures is osteoporosis. In elderly and
      multimorbid patients, the complications of conservative therapy can sometimes be
      severe. In the meantime, good outcomes with regard to pain reduction and improved
      mobility are achieved with CT-assisted balloon sacroplasty. We report on the
      successful simultaneous treatment of a bilateral osteoporosis-related
      insufficiency fracture of the sacrum. 

PMID- 25763085
TI  - Ultrasound-guided fine needle aspiration cytology in the assessment of cervical
      metastasis in patients undergoing elective neck dissection.
AB  - BACKGROUND: In head and neck cancer patients, diagnosis of metastatic cervical
      adenopathy is essential for treatment planning and prognosis assessment.
      Treatment of patients with head and neck cancer with clinically negative cervical
      lymph node (N0) remains controversial. While routine neck treatment would result
      in overtreatment in many patients, observation may delay the diagnosis and
      decrease the patients' survival. OBJECTIVES: To gain insights into the unclear
      questions regarding the value of diagnostic modalities in patients with N0 neck,
      this study was designed to compare the diagnostic efficacy of palpation,
      ultrasonography (US) and ultrasound-guided fine needle aspiration (USGFNA) in
      detecting cervical lymph node metastasis. PATIENTS AND METHODS: Forty-two
      patients with head and neck cancer who underwent US and USGFNA prior to elective
      neck dissection were studied. Histopathologic findings of the neck specimens were
      compared with each diagnostic technique. RESULTS: Of the 53 neck dissection
      specimens, histopathology showed metastases in 16 cases. The overall accuracy of
      USGFNA, US and palpation was 96%, 68% and 70%, respectively. The specificity of
      USGFNA was superior to palpation and US alone. USGFNA had the highest
      sensitivity, predictive value and accuracy in detecting cervical metastases
      compared with other performed tests. CONCLUSIONS: In our study, USGFNA was
      superior to palpation and US in detecting metastasis in clinically negative
      necks. This method can be recommended as a diagnostic tool in preoperative
      assessment of patients without palpable metastasis, but further investigations
      are needed before this modality could be considered as an alternative to elective
      neck dissection.

PMID- 25763086
TI  - Relationship between carotid artery calcification detected in dental panoramic
      images and hypertension and myocardial infarction.
AB  - BACKGROUND: Carotid artery calcification may be related to cerebrovascular
      accident, which may result in death or physical and mental disabilities in
      survivors. OBJECTIVES: Our purpose is to study the association of carotid artery
      calcification (CAC) on dental panoramic radiographs and two risk factors of
      cerebrovascular accident (CVA) including hypertension and myocardial infarction
      (MI). PATIENTS AND METHODS: Panoramic images of 200 patients that were all women
      above 50 years of age (a population suffering from vascular diseases) were
      investigated. All panoramic images were provided under similar conditions in
      terms of the type of panoramic radiograph equipment, type of applied films and
      the automatic film processor. Then, the patients answered questions about MI
      history and taking antihypertensive drugs. We also measured the blood pressure of
      patients in two separate surveys. Data analysis was performed by SPSS statistical
      program. We used Exact Fisher test and Chi-Square test at a significant level of
      less than 0.05 to study the effect of these variables on the occurrence of
      carotid artery calcification. RESULTS: Among 200 studied samples, 22 of the
      patients (11%) had carotid artery calcification on the dental panoramic
      radiograph. In total, 52 patients (26%) had hypertension and four people (2%) had
      a history of MI. Eleven individuals among patients suffering from hypertension
      (21.2%) and three individuals among patients with a history of MI (75%)
      demonstrated CAC on dental panoramic images . CONCLUSIONS: The relationship
      between CAC found on dental panoramic radiographs and two CVA risk factors-
      hypertension and MI-- was significant. Therefore, it seems that detection of CAC
      on panoramic images of dental patients must be considered by dentists.

PMID- 25763087
TI  - Temporal Bone Measurements; A Comparison Between Rendered Spiral CT and Surgery.
AB  - BACKGROUND: Accurate radiological assessment of the anatomical features of the
      temporal bone is crucial to prevent damage to vital elements in this area during
      surgery. Knowing the approximate location of specific temporal bone related
      landmarks in advance is very important for planning surgery. OBJECTIVES: This
      study compared findings from computed tomography images with those observed
      directly during ear surgery. PATIENTS AND METHODS: Patients with various
      pathologies of the ear who needed surgery were referred to an imaging center for
      a spiral CT scan of the temporal bone. The following parameters were measured by
      a radiologist and also later recorded by the surgeon during surgery: 1) The
      distance between the postero-superior border of the outer ear canal and the
      sigmoid sinus; 2) The distance between the dome of the lateral semicircular canal
      and the mastoid cortex; and 3) The distance between the external surface of the
      incus and the mastoid cortex. RESULTS: Twenty cases were included. In the three
      measurements performed in this study, only the first parameter (distance between
      the canal and the sigmoid sinus) was significantly different between the direct
      measurement made during surgery and that obtained from CT scans. There was no
      significant difference in the measurements of the distance between the dome of
      the lateral semicircular canal and the bone cortex, and the distance between the
      external surface of the incus and the surface of the bone cortex. CONCLUSIONS:
      Our study shows in terms of figures that measurements of features of the temporal
      bone made from spiral CT scan images and those directly obtained during surgery
      are similar to an adequate extent.

PMID- 25763088
TI  - Polyploidy Analysis and Attenuation of Oxidative Stress in Hepatic Tissue of STZ
      Induced Diabetic Rats Treated with an Aqueous Extract of Vochysia rufa.
AB  - Diabetes mellitus (DM) is characterized by hyperglycemia and alterations in the
      metabolism of lipids, carbohydrates, and proteins. Due to its hypoglycemic effect
      Vochysia rufa is frequently used in Uberlandia, Brazil, to treat DM. Despite its
      popularity, there is little information about its effect on hepatic tissue.
      Therefore, we evaluated the histoarchitecture, oxidative stress parameters, and
      polyploidy of liver tissue from streptozotocin- (STZ-) induced diabetic rats
      treated with aqueous extract of Vochysia rufa (AEV). Histology was determined by
      fixing the livers, processing, and staining with HE. Oxidative stress was
      determined by evaluating CAT, GPx, and SOD activity in liver homogenates and
      hepatic mitochondria fraction and by measuring GST, GSH levels and lipid
      peroxidation (MDA). Polyploidy was determined by subjecting isolated hepatocyte
      nuclei to flow cytometry. In the diabetic group, GST activity and GSH rates
      decreased whereas liver homogenate analysis showed that GPx, SOD activity and MDA
      increased. AEV treatment restored all parameters to normal levels. The oxidative
      stress analysis of hepatic mitochondria fraction showed similar results. Lower
      polyploid cell populations were found in the diabetic rat livers, even after
      glibenclamide treatment. Thus, AEV treatment efficiently reduced hepatic
      oxidative stress caused by STZ-induced diabetes and produced no morphological
      changes in the histological analysis. 

PMID- 25763089
TI  - Actigraph evaluation of acupuncture for treating restless legs syndrome.
AB  - We evaluated the effects of acupuncture in patients with restless legs syndrome
      (RLS) by actigraph recordings. Among the 38 patients with RLS enrolled, 31 (M =
      12, F = 19; mean age, 47.2 +/- 9.7 years old) completed the study. Patients were
      treated with either standard acupuncture (n = 15) or randomized acupuncture (n =
      16) in a single-blind manner for 6 weeks. Changes in nocturnal activity (NA) and
      early sleep activity (ESA) between week 0 (baseline), week 2, week 4, and week 6
      were assessed using leg actigraph recordings, the International Restless Legs
      Syndrome Rating Scale (IRLSRS), and Epworth Sleepiness Scale (ESS). Standard but
      not randomized acupuncture reduced the abnormal leg activity of NA and ESA
      significantly in week 2, week 4, and week 6 based on the changes in the clinical
      scores for IRLSRS and ESS in week 4 and week 6 compared with the baseline. No
      side effects were observed. The results indicate that standard acupuncture might
      improve the abnormal leg activity in RLS patients and thus is a potentially
      suitable integrative treatment for long-term use. 

PMID- 25763090
TI  - Differences in the Properties of the Radial Artery between Cun, Guan, Chi, and
      Nearby Segments Using Ultrasonographic Imaging: A Pilot Study on Arterial Depth,
      Diameter, and Blood Flow.
AB  - Aim of the Study. The three conventional pulse-diagnostic palpation locations
      (PLs) on both wrists are Cun, Guan, and Chi, and each location reveals different
      clinical information. To identify anatomical or hemodynamic specificity, we used
      ultrasonographic imaging to determine the arterial diameter, radial artery depth,
      and arterial blood flow velocity at the three PLs and at nearby non-PL segments.
      Methods. We applied an ultrasound scanner to 44 subjects and studied the changes
      in the arterial diameter and depth as well as in the average/maximum blood flow
      velocities along the radial artery at three PLs and three non-PLs located more
      proximally than Chi. Results. All of the measurements at all of the PLs were
      significantly different (P < 0.01). Artery depth was significantly different
      among the non-PLs; however, this difference became insignificant after
      normalization to the arm circumference. Conclusions. Substantial changes in the
      hemodynamic and anatomical properties of the radial artery around the three PLs
      were insignificant at the nearby non-PLs segments. This finding may provide a
      partial explanation for the diagnostic use of "Cun, Guan, and Chi.". 

PMID- 25763091
TI  - Electroacupuncture stimulates remodeling of extracellular matrix by inhibiting
      apoptosis in a rabbit model of disc degeneration.
AB  - The present study was designed to determine whether EA stimulates remodeling of
      extracellular matrix by inhibiting apoptosis in degenerated disc. 40 rabbits were
      randomly assigned to one of the four groups. Animal model was established by a
      loading device. Magnetic resonance imaging and Pfirrmann's classification were
      obtained to evaluate both the model and the EA treatment on disc degeneration.
      The ultrastructure of discs was observed by TEM. Apoptosis involvement was
      determined with TUNEL staining and western blot for the protein expression of Bax
      and Bcl-2. The results indicated that EA intervention decreased the MRI grades.
      TEM analysis showed an apparent remodeling and rearrangement of disc ECM after EA
      intervention for 28 days. The number of TUNEL-positive cells in the EA group was
      significantly lower than that in the compression group. The protein expression
      demonstrated an antiapoptosis effect mediated by EA. Increased expression of Bcl
      2 proteins and reduced Bax protein expression were detected after 28 days
      treatment. It was concluded that antiapoptosis pathway probably participates in
      the mechanism of EA stimulating the remodeling of ECM in disc degeneration. 

PMID- 25763092
TI  - Relaxant action of plumula nelumbinis extract on mouse airway smooth muscle.
AB  - The traditional herb Plumula Nelumbinis is widely used in the world because it
      has many biological activities, such as anti-inflammation, antioxidant,
      antihypertension, and butyrylcholinesterase inhibition. However, the action of
      Plumula Nelumbinis on airway smooth muscle (ASM) relaxation has not been
      investigated. A chloroform extract of Plumula Nelumbinis (CEPN) was prepared,
      which completely inhibited precontraction induced by high K(+) in a concentration
      dependent manner in mouse tracheal rings, but it had no effect on resting
      tension. CEPN also blocked voltage-dependent L-type Ca(2+) channel- (VDCC-)
      mediated currents. In addition, ACh-induced precontraction was also completely
      blocked by CEPN and partially inhibited by nifedipine or pyrazole 3. Besides,
      CEPN partially reduced ACh-activated nonselective cation channel (NSCC) currents.
      Taken together, our data demonstrate that CEPN blocked VDCC and NSCC to inhibit
      Ca(2+) influx, resulting in relaxation of precontracted ASM. This finding
      indicates that CEPN would be a candidate of new potent bronchodilators. 

PMID- 25763093
TI  - Shuangshen Ningxin Capsule, a Traditional Chinese Medicinal Preparation,
      Alleviates Myocardial Ischemia through Autophagy Regulation.
AB  - Shuangshen Ningxin capsule (SSNX), a modern Chinese formula, has been used to
      treat cardiovascular diseases in Eastern Asia. Our study focuses on the autophagy
      regulation of SSNX against coronary artery injuries. Myocardial infarction model
      was established in Chinese miniswines (CMS) by coronary artery balloon injury.
      SSNX was administered to the CMS for 8 weeks with 4 mg/kg or 16 mg/kg. Myocardial
      cells were incubated with 20% SSNX medicated serum for 2 hours. Assays were
      performed to detect the effects of SSNX on (i) coronary artery diameter by
      angiography, (ii) hemodynamics by noninvasive hemodynamic monitoring system,
      (iii) plaque burden and plaque volume by intravenous ultrasound (iv) coronary
      artery histology by H&E staining, (v) autophagosome by transmission electron
      microscopy, (vi) lactate dehydrogenase (LDH) leakage, and (vii) Beclin-1 and LC3
      I/II expressions by Western blot. The results showed that CMS treated with SSNX
      exhibited the correction for the disturbed cardiac hemodynamics, increase of
      coronary artery diameter, reduction of high plaque burden and plaque volume, and
      decrease of LDH. The inhibitory effect of SSNX on CMS autophagy was demonstrated
      by the reduction of autophagosome and the downregulation of beclin-1 and LC3
      I/II. SSNX may protect coronary artery and increase the stability of plaque
      through the suppression of myocardial cellular autophagy, which suggests the
      potentially therapeutic effect of SSNX on ischemic cardiovascular disease. 

PMID- 25763094
TI  - Inhibitory Effects of Chrysanthemum boreale Essential Oil on Biofilm Formation
      and Virulence Factor Expression of Streptococcus mutans.
AB  - The aim of the study was to evaluate the antibacterial activity of essential oil
      extracted from Chrysanthemum boreale (C. boreale) on Streptococcus mutans (S.
      mutans). To investigate anticariogenic properties, and bacterial growth, acid
      production, biofilm formation, bacterial adherence of S. mutans were evaluated.
      Then gene expression of several virulence factors was also evaluated. C. boreale
      essential oil exhibited significant inhibition of bacterial growth, adherence
      capacity, and acid production of S. mutans at concentrations 0.1-0.5 mg/mL and
      0.25-0.5 mg/mL, respectively. The safranin staining and scanning electron
      microscopy results showed that the biofilm formation was also inhibited. The
      result of live/dead staining showed the bactericidal effect. Furthermore, real
      time PCR analysis showed that the gene expression of some virulence factors such
      as gtfB, gtfC, gtfD, gbpB, spaP, brpA, relA, and vicR of S. mutans was
      significantly decreased in a dose dependent manner. In GC and GC-MS analysis,
      seventy-two compounds were identified in the oil, representing 85.42% of the
      total oil. The major components were camphor (20.89%), beta-caryophyllene
      (5.71%), alpha-thujone (5.46%), piperitone (5.27%), epi-sesquiphellandrene
      (5.16%), alpha-pinene (4.97%), 1,8-cineole (4.52%), beta-pinene (4.45%), and
      camphene (4.19%). These results suggest that C. boreale essential oil may inhibit
      growth, adhesion, acid tolerance, and biofilm formation of S. mutans through the
      partial inhibition of several of these virulence factors. 

PMID- 25763095
TI  - Yang/Qi invigoration: an herbal therapy for chronic fatigue syndrome with yang
      deficiency?
AB  - According to traditional Chinese medicine (TCM) theory, Yang and Qi are driving
      forces of biological activities in the human body. Based on the crucial role of
      the mitochondrion in energy metabolism, we propose an extended view of Yang and
      Qi in the context of mitochondrion-driven cellular and body function. It is of
      interest that the clinical manifestations of Yang/Qi deficiencies in TCM resemble
      those of chronic fatigue syndrome in Western medicine, which is pathologically
      associated with mitochondrial dysfunction. By virtue of their ability to enhance
      mitochondrial function and its regulation, Yang- and Qi-invigorating tonic herbs,
      such as Cistanches Herba and Schisandrae Fructus, may therefore prove to be
      beneficial in the treatment of chronic fatigue syndrome with Yang deficiency. 

PMID- 25763096
TI  - Understanding stable bi-female grouping in gibbons: feeding competition and
      reproductive success.
AB  - INTRODUCTION: Species of the order Primates are highly gregarious with most
      species living in permanent heterosexual social groups. According to theory in
      socioecology maximum social group size is limited by rates of intra-group feeding
      competition and associated increases in travel costs. Unlike other hylobatids,
      which are predominantly pair living, cao vit gibbons (Nomascus nasutus), and two
      other species of crested gibbon (Nomascus spp.) living in northern seasonal
      forest, regularly exhibit larger bi-female groups. To better understand the
      ability of northern gibbons to live in stable bi-female groups, we examined food
      distribution, feeding competition and reproductive success over a period of six
      years in a small cao vit gibbon population at Bangliang, Guangxi, China. RESULTS:
      In general, we found weak evidences for within-group contest or scramble
      competition in our two study groups, which we attribute to high spatial and
      temporal heterogeneity in the distribution of their important food species.
      Nevertheless, the larger of the two groups studied increased feeding time and
      group spread during lean periods, factors that may limit cao vit gibbon group
      size to a maximum of two breeding females. Relative to tropical pair-living
      gibbons, there is no evidence that cao vit gibbons travel farther or spend more
      time feeding, but they did consume more leaves and buds and less fruit and figs.
      Despite their highly folivorous diet, the average inter-birth interval is
      comparable to tropical gibbon populations, and the survival rate of infants and
      juveniles in our study groups is high. CONCLUSION: Cao vit gibbons do not suffer
      obvious costs in terms of feeding competition and reproductive success by living
      in bi-female groups, but within-group feeding competition may determine the upper
      the limit of cao vit gibbon group size to a maximum of two breeding females.
      These findings contribute to a growing body of evidence that bi-female grouping
      can be a stable grouping pattern of gibbons in certain habitats and further
      emphasize the flexibility of gibbon social organization.

PMID- 25763097
TI  - Intractable hiccups (singultus) abolished by risperidone, but not by haloperidol.
AB  - Hiccups or singulata are rhythmic involuntary movements of the diaphragm, caused
      by a variety of conditions that interfere with the functions of the nerve nuclei
      in the medulla and supra-spinal hiccup center. Although neurotransmitters and
      receptors involved in the pathophysiology of hiccups are not defined well,
      dopamine has been considered to play an important role. In some cases,
      chlorpromazine or other antipsychotics are used for the treatment of intractable
      hiccups but their efficacy is often limited. This report involves an 18-year-old
      patient who experienced two episodes of intractable hiccups triggered by stress,
      which lasted for weeks or even months. In both episodes, haloperidol was
      initially used, but there was no significant effect. In contrast, risperidone,
      the second-generation antipsychotic that possesses a dopamine-serotonin
      antagonist property, completely abolished the hiccups 6 hours after
      administration. This is one of few case reports in which two antipsychotics were
      challenged for a single patient with hiccups, and the effects of the drugs were
      obviously different. Our finding suggests that, in addition to dopaminergic
      system, the serotonergic systems may be involved in the pathophysiology of some
      hiccup cases and that the serotonin-acting antipsychotics such as risperidone
      should be considered as a choice in the drug treatment of intractable hiccups. 

PMID- 25763098
TI  - Acute phosphine poisoning on board a bulk carrier: analysis of factors leading to
      a fatal case.
AB  - OBJECTIVES: To determine accidental factors, clinical presentation and medical
      care in cases of seafarers presenting phosphine poisoning symptoms on board a
      bulk carrier. To consider primary prevention of this pathology, which can have
      extremely severe consequences. METHODS: To analyse circumstances resulting in
      toxic exposure to phosphine in the sea transport sector. To obtain information
      from medical reports regarding the seafarer's rescue. To identify the causes of
      this accidental poisoning and how to establish an early, appropriate diagnosis
      thus avoiding other cases. RESULTS: In February 2008, on board a bulk carrier
      with a cargo of peas, a 56-year-old seafarer with intense abdominal and chest
      pains, associated with dizziness, was rescued by helicopter 80 miles away from
      the coast. Despite being admitted rapidly to hospital, his heart rate decreased
      associated with respiratory distress. He lost consciousness and convulsed. He
      finally died of pulmonary oedema, major metabolic acidosis and acute multi organ
      failure. The following day, the captain issued a rescue call from the same vessel
      for a 41-year-old man also with abdominal pain, vomiting and dizziness. The ECG
      only revealed type 1 Brugada syndrome. Then 11 other seafarers were evacuated for
      observation. 3 showed clinical abnormalities. Collective poisoning was suspected.
      Medical team found out that aluminium phosphide pellets had been put in the
      ship's hold for pest control before the vessel's departure. Seafarers were
      poisoned by phosphine gas spreading through cabins above the hold. It was found
      that the compartments and ducts were not airtight. CONCLUSION: Unfortunately, a
      seafarer on board a bulk carrier died in 2008 because of acute phosphine
      poisoning. Fumigation performed using this gas needs to be done with extreme
      care. Systematic checks need to be carried out before sailing to ensure that the
      vessel's compartments are airtight.

PMID- 25763099
TI  - Bone-added periodontal plastic surgery: a new approach in esthetic dentistry.
AB  - This article proposes a combined technique including bone grafting, connective
      tissue graft, and coronally advanced flap to create some space for simultaneous
      bone regrowth and root coverage. A 23 year-old female was referred to our private
      clinic with a severe class II Miller recession and lack of attached gingiva. The
      suggested treatment plan comprised of root coverage combined with xenograft bone
      particles. The grafted area healed well and full coverage was achieved at 12
      month follow-up visit. Bone-added periodontal plastic surgery can be considered
      as a practical procedure for management of deep gingival recession without buccal
      bone plate. 

PMID- 25763100
TI  - The impact of different multi-walled carbon nanotubes on the X-band microwave
      absorption of their epoxy nanocomposites.
AB  - BACKGROUND: Carbon nanotube (CNT) characteristics, besides the processing
      conditions, can change significantly the microwave absorption behavior of
      CNT/polymer composites. In this study, we investigated the influence of three
      commercial multi-walled CNT materials with various diameters and length-to
      diameter aspect ratios on the X-band microwave absorption of epoxy nanocomposites
      with CNT contents from 0.125 to 2 wt%, prepared by two dispersion methods, i.e.
      in solution with surfactant-aiding and via ball-milling. RESULTS: The laser
      diffraction particle size and TEM analysis showed that both methods produced good
      dispersions at the microscopic level of CNTs. Both a high aspect ratio resulting
      in nanotube alignment trend and good infiltration of the matrix in the individual
      nanotubes, which was indicated by high Brookfield viscosities at low CNT contents
      of CNT/epoxy dispersions, are important factors to achieve composites with high
      microwave absorption characteristics. The multi-walled carbon nanotube (MWCNT)
      with the largest aspect ratio resulted in composites with the best X-band
      microwave absorption performance, which is considerably better than that of
      reported pristine CNT/polymer composites with similar or lower thicknesses and
      CNT loadings below 4 wt%. CONCLUSIONS: A high aspect ratio of CNTs resulting in
      microscopic alignment trend of nanotubes as well as a good level of micro-scale
      CNT dispersion resulting from good CNT-matrix interactions are crucial to obtain
      effective microwave absorption performance. This study demonstrated that
      effective radar absorbing MWCNT/epoxy nanocomposites having small matching
      thicknesses of 2-3 mm and very low filler contents of 0.25-0.5 wt%, with
      microwave energy absorption in the X-band region above 90% and maximum absorption
      peak values above 97%, could be obtained via simple processing methods, which is
      promising for mass production in industrial applications. Graphical
      AbstractComparison of the X-band microwave reflection loss of epoxy composites of
      various commercial multi-walled carbon nanotube materials.

PMID- 25763101
TI  - Elimination of hydrogenase active site assembly blocks H2 production and
      increases ethanol yield in Clostridium thermocellum.
AB  - BACKGROUND: The native ability of Clostridium thermocellum to rapidly consume
      cellulose and produce ethanol makes it a leading candidate for a consolidated
      bioprocessing (CBP) biofuel production strategy. C. thermocellum also synthesizes
      lactate, formate, acetate, H2, and amino acids that compete with ethanol
      production for carbon and electrons. Elimination of H2 production could redirect
      carbon flux towards ethanol production by making more electrons available for
      acetyl coenzyme A reduction to ethanol. RESULTS: H2 production in C. thermocellum
      is encoded by four hydrogenases. Rather than delete each individually, we
      targeted hydrogenase maturase gene hydG, involved in converting the three [FeFe]
      hydrogenase apoenzymes into holoenzymes. Further deletion of the [NiFe]
      hydrogenase (ech) resulted in a mutant that functionally lacks all four
      hydrogenases. H2 production in ?hydG?ech was undetectable, and the ethanol yield
      nearly doubled to 64% of the maximum theoretical yield. Genomic analysis of ?hydG
      revealed a mutation in adhE, resulting in a strain with both NADH- and NADPH
      dependent alcohol dehydrogenase activities. While this same adhE mutation was
      found in ethanol-tolerant C. thermocellum strain E50C, ?hydG and ?hydG?ech are
      not more ethanol tolerant than the wild type, illustrating the complicated
      interactions between redox balancing and ethanol tolerance in C. thermocellum.
      CONCLUSIONS: The dramatic increase in ethanol production suggests that targeting
      protein post-translational modification is a promising new approach for
      simultaneous inactivation of multiple enzymes.

PMID- 25763102
TI  - Fungal-assisted algal flocculation: application in wastewater treatment and
      biofuel production.
AB  - BACKGROUND: The microalgal-based industries are facing a number of important
      challenges that in turn affect their economic viability. Arguably the most
      important of these are associated with the high costs of harvesting and
      dewatering of the microalgal cells, the costs and sustainability of nutrient
      supplies and costly methods for large scale oil extraction. Existing harvesting
      technologies, which can account for up to 50% of the total cost, are not
      economically feasible because of either requiring too much energy or the addition
      of chemicals. Fungal-assisted flocculation is currently receiving increased
      attention because of its high harvesting efficiency. Moreover, some of fungal and
      microalgal strains are well known for their ability to treat wastewater,
      generating biomass which represents a renewable and sustainable feedstock for
      bioenergy production. RESULTS: We screened 33 fungal strains, isolated from
      compost, straws and soil for their lipid content and flocculation efficiencies
      against representatives of microalgae commercially used for biodiesel production,
      namely the heterotrophic freshwater microalgae Chlorella protothecoides and the
      marine microalgae Tetraselmis suecica. Lipid levels and composition were analyzed
      in fungal-algal pellets grown on media containing alternative carbon, nitrogen
      and phosphorus sources from wheat straw and swine wastewater, respectively. The
      biomass of fungal-algal pellets grown on swine wastewater was used as feedstock
      for the production of value-added chemicals, biogas, bio-solids and liquid
      petrochemicals through pyrolysis. Co-cultivation of microalgae and filamentous
      fungus increased total biomass production, lipid yield and wastewater
      bioremediation efficiency. CONCLUSION: Fungal-assisted microalgal flocculation
      shows significant potential for solving the major challenges facing the
      commercialization of microalgal biotechnology, namely (i) the efficient and cost
      effective harvesting of freshwater and seawater algal strains; (ii) enhancement
      of total oil production and optimization of its composition; (iii) nutrient
      supply through recovering of the primary nutrients, nitrogen and phosphates and
      microelements from wastewater. The biomass generated was thermochemically
      converted into biogas, bio-solids and a range of liquid petrochemicals including
      straight-chain C12 to C21 alkanes which can be directly used as a glycerine-free
      component of biodiesel. Pyrolysis represents an efficient alternative strategy
      for biofuel production from species with tough cell walls such as fungi and
      fungal-algal pellets.

PMID- 25763103
TI  - Untreated Chlorella homosphaera biomass allows for high rates of cell wall glucan
      enzymatic hydrolysis when using exoglucanase-free cellulases.
AB  - BACKGROUND: Chlorophyte microalgae have a cell wall containing a large quantity
      of cellulose Ialpha with a triclinic unit cell hydrogen-bonding pattern that is
      more susceptible to hydrolysis than that of the cellulose Ibeta polymorphic form
      that is predominant in higher plants. This study addressed the enzymatic
      hydrolysis of untreated Chlorella homosphaera biomass using selected enzyme
      preparations, aiming to identify the relevant activity profile for the microalgae
      cellulose hydrolysis. Enzymes from Acremonium cellulolyticus, which secretes a
      complete pool of cellulases plus beta-glucosidase; Trichoderma reesei, which
      secretes a complete pool of cellulases with low beta-glucosidase; Aspergillus
      awamori, which secretes endoglucanases and beta-glucosidase; blends of T. reesei
      A. awamori or A. awamori-A. cellulolyticus enzymes; and a purified A. awamori
      beta-glucosidase were evaluated. RESULTS: The highest initial glucan hydrolysis
      rate of 140.3 mg/g/h was observed for A. awamori enzymes with high beta
      glucosidase, low endoglucanase, and negligible cellobiohydrolase activities. The
      initial hydrolysis rates when using A. cellulolyticus or T. reesei enzymes were
      significantly lower, whereas the results for the T. reesei-A. awamori and A.
      awamori-A. cellulolyticus blends were similar to that for the A. awamori enzymes.
      Thus, the hydrolysis of C. homosphaera cellulose was performed exclusively by the
      endoglucanase and beta-glucosidase activities. X-ray diffraction data showing
      negligible cellulose crystallinity for untreated C. homosphaera biomass
      corroborate these findings. The A. awamori-A. cellulolyticus blend showed the
      highest initial polysaccharide hydrolysis rate of 185.6 mg/g/h, as measured by
      glucose equivalent, in addition to the highest predicted maximum glucan
      hydrolysis yield of 47% of total glucose (w/w). T. reesei enzymes showed the
      lowest predicted maximum glucan hydrolysis yield of 25% (w/w), whereas the
      maximum yields of approximately 31% were observed for the other enzyme
      preparations. The hydrolysis yields were proportional to the enzyme beta
      glucosidase load, indicating that the endoglucanase load was not rate-limiting.
      CONCLUSIONS: High rates of enzymatic hydrolysis were achieved for untreated C.
      homosphaera biomass with enzymes containing endoglucanase and beta-glucosidase
      activities and devoid of cellobiohydrolase activity. These findings simplify the
      complexity of the enzyme pools required for the enzymatic hydrolysis of
      microalgal biomass decreasing the enzyme cost for the production of microalgae
      derived glucose syrups.

PMID- 25763104
TI  - Potential of lipid metabolism in marine diatoms for biofuel production.
AB  - BACKGROUND: Diatoms are an ecologically relevant group of microalgae that are not
      commonly considered for bio-oil production even if they are responsible for
      massive blooms at sea. Seventeen diatom species were screened for their capacity
      to produce biomass and lipids, in relation to their growth rate. Triglyceride
      levels were also assessed as a preferential source of biofuels. RESULTS: Using
      statistical analysis, two centric diatoms, Thalassiosira weissflogii and
      Cyclotella cryptica, were selected as good candidates for oil production. Lipid
      levels significantly increased when the two diatoms were cultivated in a two
      stage process under nitrogen limitation. The effect was less pronounced in
      cultures where silicon was reduced to 20% of the standard supply. Nitrogen
      limitation did not affect growth rates but led to lipid remodeling and de novo
      synthesis of triacylglycerols. CONCLUSIONS: Triacylglycerols in T. weissflogii
      and C. cryptica can account for up to 82% and 88% of total glycerolipids, thereby
      suggesting that the two species are promising candidates for large-scale
      experimentation for biofuel production.

PMID- 25763105
TI  - Improved glycerol utilization by a triacylglycerol-producing Rhodococcus opacus
      strain for renewable fuels.
AB  - BACKGROUND: Glycerol generated during renewable fuel production processes is
      potentially an attractive substrate for the production of value-added materials
      by fermentation. An engineered strain MITXM-61 of the oleaginous bacterium
      Rhodococcus opacus produces large amounts of intracellular triacylglycerols
      (TAGs) for lipid-based biofuels on high concentrations of glucose and xylose.
      However, on glycerol medium, MITXM-61 does not produce TAGs and grows poorly. The
      aim of the present work was to construct a TAG-producing R. opacus strain capable
      of high-cell-density cultivation at high glycerol concentrations. RESULTS: An
      adaptive evolution strategy was applied to improve the conversion of glycerol to
      TAGs in R. opacus MITXM-61. An evolved strain, MITGM-173, grown on a defined
      medium with 16 g L(-1) glycerol, produced 2.3 g L(-1) of TAGs, corresponding to
      40.4% of the cell dry weight (CDW) and 0.144 g g(-1) of TAG yield per glycerol
      consumed. MITGM-173 was able to grow on high concentrations (greater than 150 g
      L(-1)) of glycerol. Cultivated in a medium containing an initial concentration of
      20 g L(-1) glycerol, 40 g L(-1) glucose, and 40 g L(-1) xylose, MITGM-173 was
      capable of simultaneously consuming the mixed substrates and yielding 13.6 g L(
      1) of TAGs, representing 51.2% of the CDM. In addition, when 20 g L(-1) glycerol
      was pulse-loaded into the culture with 40 g L(-1) glucose and 40 g L(-1) xylose
      at the stationary growth phase, MITGM-173 produced 14.3 g L(-1) of TAGs
      corresponding to 51.1% of the CDW although residual glycerol in the culture was
      observed. The addition of 20 g L(-1) glycerol in the glucose/xylose mix resulted
      in a TAG yield per glycerol consumed of 0.170 g g(-1) on the initial addition and
      0.279 g g(-1) on the pulse addition of glycerol. CONCLUSION: We have generated a
      TAG-producing R. opacus MITGM-173 strain that shows significantly improved
      glycerol utilization in comparison to the parental strain. The present study
      demonstrates that the evolved R. opacus strain shows significant promise for
      developing a cost-effective bioprocess to generate advanced renewable fuels from
      mixed sugar feedstocks supplemented with glycerol.

PMID- 25763106
TI  - Assembly of lipase and P450 fatty acid decarboxylase to constitute a novel
      biosynthetic pathway for production of 1-alkenes from renewable triacylglycerols
      and oils.
AB  - BACKGROUND: Biogenic hydrocarbons (biohydrocarbons) are broadly accepted to be
      the ideal 'drop-in' biofuel alternative to petroleum-based fuels due to their
      highly similar chemical composition and physical characteristics. The biological
      production of aliphatic hydrocarbons is largely dependent on engineering of the
      complicated enzymatic network surrounding fatty acid biosynthesis. RESULT: In
      this work, we developed a novel system for bioproduction of terminal fatty
      alkenes (1-alkenes) from renewable and low-cost triacylglycerols (TAGs) based on
      the lipase hydrolysis coupled to the P450 catalyzed decarboxylation. This
      artificial biosynthetic pathway was constituted using both cell-free systems
      including purified enzymes or cell-free extracts, and cell-based systems
      including mixed resting cells or growing cells. The issues of high cost of fatty
      acid feedstock and complicated biosynthesis network were addressed by replacement
      of the de novo biosynthesized fatty acids with the fed cheap TAGs. This
      recombinant tandem enzymatic pathway consisting of the Thermomyces lanuginosus
      lipase (Tll) and the P450 fatty acid decarboxylase OleTJE resulted in the
      production of 1-alkenes from purified TAGs or natural oils with 6.7 to 46.0%
      yields. CONCLUSION: Since this novel hydrocarbon-producing pathway only requires
      two catalytically efficient enzymatic steps, it may hold great potential for
      industrial application by fulfilling the large-scale and cost-effective
      conversion of renewable TAGs into biohydrocarbons. This work highlights the power
      of designing and implementing an artificial pathway for production of advanced
      biofuels.

PMID- 25763107
TI  - A novel arabinose-inducible genetic operation system developed for Clostridium
      cellulolyticum.
AB  - BACKGROUND: Clostridium cellulolyticum and other cellulolytic Clostridium strains
      are natural producers of lignocellulosic biofuels and chemicals via the
      consolidated bioprocessing (CBP) route, and systems metabolic engineering is
      indispensable to meet the cost-efficient demands of industry. Several genetic
      tools have been developed for Clostridium strains, and an efficient and stringent
      inducible genetic operation system is still required for the precise regulation
      of the target gene function. RESULTS: Here, we provide a stringent arabinose
      inducible genetic operation (ARAi) system for C. cellulolyticum, including an
      effective gene expression platform with an oxygen-independent fluorescent
      reporter, a sensitive MazF-based counterselection genetic marker, and a precise
      gene knock-out method based on an inducible ClosTron system. A novel arabinose
      inducible promoter derived from Clostridium acetobutylicum is employed in the
      ARAi system to control the expression of the target gene, and the gene expression
      can be up-regulated over 800-fold with highly induced stringency. The inducible
      ClosTron method of the ARAi system decreases the off-target frequency from 100%
      to 0, which shows the precise gene targeting in C. cellulolyticum. The inducible
      effect of the ARAi system is specific to a universal carbon source L-arabinose,
      implying that the system could be used widely for clostridial strains with
      various natural substrates. CONCLUSIONS: The inducible genetic operation system
      ARAi developed in this study, containing both controllable gene expression and
      disruption tools, has the highest inducing activity and stringency in Clostridium
      by far. Thus, the ARAi system will greatly support the efficient metabolic
      engineering of C. cellulolyticum and other mesophilic Clostridium strains for
      lignocellulose bioconversion.

PMID- 25763108
TI  - Missed signs of autonomic dysreflexia in a tetraplegic patient after incorrect
      placement of urethral Foley catheter: a case report.
AB  - BACKGROUND: Autonomic dysreflexia is poorly recognised outside of spinal cord
      injury centres, and may result in adverse outcomes including mortality from
      delayed diagnosis and treatment. We present a spinal cord injury patient, who
      developed autonomic dysreflexia following incorrect placement of urethral Foley
      catheter. Health professionals failed to recognise signs and symptoms of
      autonomic dysreflexia as well as its significance in this tetraplegic patient.
      CASE PRESENTATION: A tetraplegic patient started sweating profusely following
      insertion of a Foley catheter per urethra. The catheter was draining urine; there
      was no bypassing, no bleeding per urethra, and no haematuria. Patient's wife, who
      had been looking after her tetraplegic husband for more than forty years, told
      the health professionals that the catheter might have been placed incorrectly but
      her concerns were ignored. Ultrasound scan of urinary tract revealed no urinary
      calculi, no hydronephrosis. The balloon of Foley catheter was not seen in urinary
      bladder but this finding was not recognised by radiologist and spinal cord
      physician. Patient continued to sweat profusely; therefore, CT of pelvis was
      performed, but there was a delay of ten days. CT revealed the balloon of Foley
      catheter in the over-stretched prostate-membranous urethra; the tip of catheter
      was not located within the urinary bladder but was lying distal to bladder neck.
      Flexible cystoscopy was performed and Foley catheter was inserted into the
      bladder over a guide wire. The intensity of sweating decreased; noxious stimuli
      arising from traumatised urethra might take a long while to settle. CONCLUSION:
      Inserting a catheter in a tetraplegic patient should be carried out by a senior
      health professional, who is familiar with spasm of bladder neck which occurs
      frequently in tetraplegic patients. Facilities for urgent CT scan should be
      available to check the position of Foley catheter in spinal cord injury patients
      when a patient manifests signs and symptoms of autonomic dysreflexia following
      insertion of a urethral catheter. When an isolated symptom such as flushing or
      sweating is noticed in a tetraplegic patient, doctors should seek out other
      signs/symptoms of autonomic dysreflexia.

PMID- 25763109
TI  - Comparative methylome analysis identifies new tumour subtypes and biomarkers for
      transformation of nephrogenic rests into Wilms tumour.
AB  - BACKGROUND: Wilms tumours (WTs) are characterised by several hallmarks that
      suggest epimutations such as aberrant DNA methylation are involved in tumour
      progression: loss of imprinting at 11p15, lack of recurrent mutations and
      formation of nephrogenic rests (NRs), which are lesions of retained
      undifferentiated embryonic tissue that can give rise to WTs. METHODS: To identify
      such epimutations, we performed a comprehensive methylome analysis on 20 matched
      trios of micro-dissected WTs, NRs and surrounding normal kidneys (NKs) using
      Illumina Infinium HumanMethylation450 Bead Chips and functionally validated
      findings using RNA sequencing. RESULTS: Comparison of NRs with NK revealed
      prominent tissue biomarkers: 629 differentially methylated regions, of which 55%
      were hypermethylated and enriched for domains that are bivalent in embryonic stem
      cells and for genes expressed during development (P = 2.49 * 10(-5)). Comparison
      of WTs with NRs revealed two WT subgroups; group-2 WTs and NRs were
      epigenetically indistinguishable whereas group-1 WTs showed an increase in
      methylation variability, hypomethylation of renal development genes,
      hypermethylation and relative loss of expression of cell adhesion genes and known
      and potential new WT tumour suppressor genes (CASP8, H19, MIR195, RB1 and
      TSPAN32) and was strongly associated with bilateral disease (P = 0.032).
      Comparison of WTs and NRs to embryonic kidney highlighted the significance of
      polycomb target methylation in Wilms tumourigenesis. CONCLUSIONS: Methylation
      levels vary during cancer evolution. We have described biomarkers related to WT
      evolution from its precursor NRs which may be useful to differentiate between
      these tissues for patients with bilateral disease.

PMID- 25763110
TI  - Haploinsufficiency of Hedgehog interacting protein causes increased emphysema
      induced by cigarette smoke through network rewiring.
AB  - BACKGROUND: The HHIP gene, encoding Hedgehog interacting protein, has been
      implicated in chronic obstructive pulmonary disease (COPD) by genome-wide
      association studies (GWAS), and our subsequent studies identified a functional
      upstream genetic variant that decreased HHIP transcription. However, little is
      known about how HHIP contributes to COPD pathogenesis. METHODS: We exposed Hhip
      haploinsufficient mice (Hhip (+/-) ) to cigarette smoke (CS) for 6 months to
      model the biological consequences caused by CS in human COPD risk-allele carriers
      at the HHIP locus. Gene expression profiling in murine lungs was performed
      followed by an integrative network inference analysis, PANDA (Passing Attributes
      between Networks for Data Assimilation) analysis. RESULTS: We detected more
      severe airspace enlargement in Hhip (+/-) mice vs. wild-type littermates (Hhip
      (+/+) ) exposed to CS. Gene expression profiling in murine lungs suggested
      enhanced lymphocyte activation pathways in CS-exposed Hhip (+/-) vs. Hhip (+/+)
      mice, which was supported by increased numbers of lymphoid aggregates and
      enhanced activation of CD8+ T cells after CS-exposure in the lungs of Hhip (+/-)
      mice compared to Hhip (+/+) mice. Mechanistically, results from PANDA network
      analysis suggested a rewired and dampened Klf4 signaling network in Hhip (+/-)
      mice after CS exposure. CONCLUSIONS: In summary, HHIP haploinsufficiency
      exaggerated CS-induced airspace enlargement, which models CS-induced emphysema in
      human smokers carrying COPD risk alleles at the HHIP locus. Network modeling
      suggested rewired lymphocyte activation signaling circuits in the HHIP
      haploinsufficiency state.

PMID- 25763111
TI  - Effects of Roux-en-Y gastric bypass on fasting and postprandial inflammation
      related parameters in obese subjects with normal glucose tolerance and in obese
      subjects with type 2 diabetes.
AB  - BACKGROUND: Obesity is characterized by low grade inflammation and an altered
      secretion of inflammatory cytokines from the adipose tissue. Weight loss has
      shown to reduce inflammation; however, changes in cytokine profiles during
      massive weight loss are not well described. The present study explored the
      hypothesis that Roux-en-Y gastric bypass (RYGB) reduces circulating levels of pro
      inflammatory cytokines, while increasing anti-inflammatory cytokines in obese
      subjects with type 2 diabetes (T2D) and in obese normal glucose tolerant (NGT)
      subjects. METHODS: Thirteen obese subjects with T2D [weight; 129 +/- 14 kg,
      glycated hemoglobin (HbA1c); 7.0 +/- 0.9%, body mass index (BMI); 43.2 +/- 5.3
      kg/m(2), mean +/- SD] and twelve matched obese NGT subjects [weight; 127 +/- 15
      kg, HbA1c; 5.5 +/- 0.4%, BMI; 41.5 +/- 4.8 kg/m(2), mean +/- SD] were examined
      before, one week, three months, and one year after surgery. Interleukin (IL)-6,
      leptin, adiponectin, IL-8, transforming growth factor beta (TGF-beta), and the
      incretin hormone glucagon-like peptide-1 (GLP-1) were measured in the fasting
      state and during a liquid meal. Insulin resistance was evaluated by HOMA-IR.
      RESULTS: Weight loss did not differ between the two groups. Before surgery, HbA1c
      was higher and HOMA-IR lower in T2D patients, however, converged to the values of
      NGT subjects one year after surgery. Circulating cytokine concentrations did not
      differ between the two groups at any time point. One week after surgery,
      circulating IL-6 and IL-8 were increased, while adiponectin and leptin were
      reduced compared with pre-surgical concentrations. Three months after surgery, IL
      8 was increased, leptin was reduced, and no change was observed for IL-6, TGF
      beta, and adiponectin. One year after surgery, concentrations of IL-6, TGF-beta,
      and leptin were significantly reduced compared to before surgery, while
      adiponectin was significantly increased. CONCLUSIONS: One year after RYGB,
      fasting concentrations of IL-6 and leptin were reduced, while no changes were
      observed in IL-8. TGF-beta was decreased and adiponectin increased in both T2D
      and NGT obese subjects. This study is the first to examine IL-8 and TGF-beta in
      obese subject after RYGB. Resolution of inflammation could offer a potential
      explanation for the health improvement associated with major weight loss after
      bariatric surgery. TRIAL REGISTRATION: http://www.clinicaltrials.gov
      (NCT01579981).

PMID- 25763113
TI  - Genome-wide DNA methylation analysis reveals estrogen-mediated epigenetic
      repression of metallothionein-1 gene cluster in breast cancer.
AB  - BACKGROUND: Recent genome-wide analysis has shown that DNA methylation spans long
      stretches of chromosome regions consisting of clusters of contiguous CpG islands
      or gene families. Hypermethylation of various gene clusters has been reported in
      many types of cancer. In this study, we conducted methyl-binding domain capture
      (MBDCap) sequencing (MBD-seq) analysis on a breast cancer cohort consisting of 77
      patients and 10 normal controls, as well as a panel of 38 breast cancer cell
      lines. RESULTS: Bioinformatics analysis determined seven gene clusters with a
      significant difference in overall survival (OS) and further revealed a distinct
      feature that the conservation of a large gene cluster (approximately 70 kb)
      metallothionein-1 (MT1) among 45 species is much lower than the average of all
      RefSeq genes. Furthermore, we found that DNA methylation is an important
      epigenetic regulator contributing to gene repression of MT1 gene cluster in both
      ERalpha positive (ERalpha+) and ERalpha negative (ERalpha-) breast tumors. In
      silico analysis revealed much lower gene expression of this cluster in The Cancer
      Genome Atlas (TCGA) cohort for ERalpha + tumors. To further investigate the role
      of estrogen, we conducted 17beta-estradiol (E2) and demethylating agent 5-aza-2'
      deoxycytidine (DAC) treatment in various breast cancer cell types. Cell
      proliferation and invasion assays suggested MT1F and MT1M may play an anti
      oncogenic role in breast cancer. CONCLUSIONS: Our data suggests that DNA
      methylation in large contiguous gene clusters can be potential prognostic markers
      of breast cancer. Further investigation of these clusters revealed that estrogen
      mediates epigenetic repression of MT1 cluster in ERalpha + breast cancer cell
      lines. In all, our studies identify thousands of breast tumor hypermethylated
      regions for the first time, in particular, discovering seven large contiguous
      hypermethylated gene clusters.

PMID- 25763112
TI  - A cross-sectional assessment of metabolic syndrome in HIV-infected people of low
      socio-economic status receiving antiretroviral therapy.
AB  - BACKGROUND: Metabolic syndrome (MetS) is a constellation of symptoms used as a
      measure to identify patients at increased risk for cardiovascular disease, type 2
      diabetes, and all-cause mortality. The results of prolonged life expectancy and
      cumulative toxic effects of antiretroviral therapy increase the chance that HIV
      can cause clinical abnormalities, including MetS. METHODS: We evaluated 89 people
      living with HIV (PLWH; mean age 48 +/- 7 years; mean duration of HIV infection 17
      +/- 12 years; 47% men; 66% African-American, 22% Hispanic, and 10% non-Hispanic
      white; and 84% unemployed) enrolled in a community-based exercise training and
      nutrition education program targeting individuals of low socio-economic status
      (SES). The prevalence of MetS characteristics and the factors associated with the
      presence of MetS were analyzed. RESULTS: One in three (33%; 12 men and 17 women)
      PLWH met ATPIII criteria for MetS. In our cohort, MetS was driven by high waist
      circumference and elevated blood pressure. In addition, higher use of protease
      inhibitors, elevated hemoglobin A1c (HbA1c), greater self-reported daily caloric
      intake and consumption of carbohydrates, sugar, added sugar, and higher glycemic
      load were found among the individuals with MetS, compared to those without it.
      Elevated HbA1c and high total sugar consumption were the strongest predictors and
      accounted for 30% of the occurrence of MetS. CONCLUSIONS: The overall prevalence
      of MetS in our PLWH cohort receiving antiretroviral therapy is higher than
      previously reported in the general population and in other PLWH cohorts.
      Additional work is needed to determine whether MetS is a more disease dependent
      or lifestyle dependent condition in PLWH.

PMID- 25763114
TI  - Vitamin B12 insufficiency induces cholesterol biosynthesis by limiting s
      adenosylmethionine and modulating the methylation of SREBF1 and LDLR genes.
AB  - BACKGROUND: The dietary supply of methyl donors such as folate, vitamin B12,
      betaine, methionine, and choline is essential for normal growth, development, and
      physiological functions through the life course. Both human and animal studies
      have shown that vitamin B12 deficiency is associated with altered lipid profile
      and play an important role in the prediction of metabolic risk, however, as of
      yet, no direct mechanism has been investigated to confirm this. RESULTS: Three
      independent clinical studies of women (i) non-pregnant at child-bearing age, (ii)
      in early pregnancy, and (iii) at delivery showed that low vitamin B12 status was
      associated with higher total cholesterol, LDL cholesterol, and cholesterol-to-HDL
      ratio. These results guided the investigation into the cellular mechanisms of
      induced cholesterol biosynthesis due to vitamin B12 deficiency, using human
      adipocytes as a model system. Adipocytes cultured in low or no vitamin B12
      conditions had increased cholesterol and homocysteine levels compared to control.
      The induction of cholesterol biosynthesis was associated with reduced s
      adenosylmethionine (AdoMet)-to-s-adenosylhomocysteine (AdoHcy) ratio, also known
      as methylation potential (MP). We therefore studied whether reduced MP could lead
      to hypomethylation of genes involved in the regulation of cholesterol
      biosynthesis. Genome-wide and targeted DNA methylation analysis identified that
      the promoter regions of SREBF1 and LDLR, two key regulators of cholesterol
      biosynthesis, were hypomethylated under vitamin B12-deficient conditions, and as
      a result, their expressions and cholesterol biosynthesis were also significantly
      increased. This finding was further confirmed by the addition of the methylation
      inhibitor, 5-aza-2'-deoxycytidine, which resulted in increased SREBF1 and LDLR
      expressions and cholesterol accumulation in vitamin B12-sufficient conditions.
      Finally, we observed that the expression of SREBF1, LDLR, and cholesterol
      biosynthesis genes were increased in adipose tissue of vitamin B12 deficient
      mothers compared to control group. CONCLUSIONS: Clinical data suggests that
      vitamin B12 deficiency is an important metabolic risk factor. Regulation of
      AdoMet-to-AdoHcy levels by vitamin B12 could be an important mechanism by which
      it can influence cholesterol biosynthesis pathway in human adipocytes.

PMID- 25763116
TI  - The impact of vaccination on influenza-related respiratory failure and mortality
      in hospitalized elderly patients over the 2013-2014 season.
AB  - BACKGROUND: Seasonal Influenza ("the flu") is a respiratory illness caused by
      influenza viruses. Yearly influenza vaccination is considered to be protective
      against illness and/or severity of illness and is recommended by CDC for all
      individuals > 6 months of age. However, the effectiveness of influenza vaccine in
      older individuals has come under question. OBJECTIVES: To describe the clinical
      characteristics and treatment outcomes of patients admitted to an academic
      tertiary care Veterans Administration hospital with influenza during the 2013
      2014 influenza season and determine the impact, if any, of prior influenza
      vaccination upon patient outcomes. METHODS: Medical electronic records were
      searched for all patients admitted to the Little Rock Veterans Administration
      Hospital with proven influenza during the 2013-2014 influenza season. Cohorts of
      vaccinated and non-vaccinated patients were then compared to determine the impact
      of prior influenza vaccination upon respiratory-failure and mortality. RESULTS:
      Seventy patients met selection criteria. Mean age was 66 years. Sixty-four (91%)
      patients had at least one underlying co-morbid condition; these conditions
      included COPD, congestive heart failure, diabetes, and cancer. 60/70 (85%) tested
      positive for Influenza A, and 43 tested positive for H1N1. Oseltamivir was
      initiated in 55 (78%) patients. Forty-four percent of the patients had been
      vaccinated. When separated by vaccination status, those who had been vaccinated
      had higher rates of ICU admission, need for mechanical or non-invasive
      ventilation, and mortality. All but mortality reached statistical significance.
      CONCLUSION: The data suggest that there was no protective effect from prior
      vaccination in preventing hospital admission, respiratory failure, and mortality
      in this population of older men admitted to the hospital with influenza.

PMID- 25763115
TI  - Replicative senescence is associated with nuclear reorganization and with DNA
      methylation at specific transcription factor binding sites.
AB  - BACKGROUND: Primary cells enter replicative senescence after a limited number of
      cell divisions. This process needs to be considered in cell culture experiments,
      and it is particularly important for regenerative medicine. Replicative
      senescence is associated with reproducible changes in DNA methylation (DNAm) at
      specific sites in the genome. The mechanism that drives senescence-associated
      DNAm changes remains unknown - it may involve stochastic DNAm drift due to
      imperfect maintenance of epigenetic marks or it is directly regulated at specific
      sites in the genome. RESULTS: In this study, we analyzed the reorganization of
      nuclear architecture and DNAm changes during long-term culture of human
      fibroblasts and mesenchymal stromal cells (MSCs). We demonstrate that telomeres
      shorten and shift towards the nuclear center at later passages. In addition, DNAm
      profiles, either analyzed by MethylCap-seq or by 450k IlluminaBeadChip
      technology, revealed consistent senescence-associated hypermethylation in regions
      associated with H3K27me3, H3K4me3, and H3K4me1 histone marks, whereas
      hypomethylation was associated with chromatin containing H3K9me3 and lamina
      associated domains (LADs). DNA hypermethylation was significantly enriched in the
      vicinity of genes that are either up- or downregulated at later passages.
      Furthermore, specific transcription factor binding motifs (e.g. EGR1, TFAP2A, and
      ETS1) were significantly enriched in differentially methylated regions and in the
      promoters of differentially expressed genes. CONCLUSIONS: Senescence-associated
      DNA hypermethylation occurs at specific sites in the genome and reflects
      functional changes in the course of replicative senescence. These results
      indicate that tightly regulated epigenetic modifications during long-term culture
      contribute to changes in nuclear organization and gene expression.

PMID- 25763119
TI  - Endourology, the initiative.

PMID- 25763117
TI  - Corneal Collagen Cross-Linking Mushroom Shape Demarcation Line Profile After
      Limited Bowman's Membrane Removal by Phototherapeutic Keratectomy.
AB  - PURPOSE: To report a corneal collagen cross-linking (CXL) mushroom shape
      demarcation line profile after limited Bowman's membrane removal by
      phototherapeutic keratectomy (PTK). METHODS: Case report. RESULTS: A twenty-one
      year-old male with progressive keratoconus underwent mechanical epithelial
      debridement (at an 8.5 mm zone) followed by PTK (at a 5.0 mm zone and in a 10 MUm
      depth) and CXL. No intra- or early postoperative complications were found.
      Evaluation of the corneal stromal demarcation line depth using anterior segment
      optical coherence tomography revealed a mushroom shape profile. CONCLUSION: It
      seems that removal of the Bowman's layer leads to greater depth of the corneal
      stromal demarcation line.

PMID- 25763120
TI  - Current status of robotic surgery in Japan.
AB  - The da Vinci S surgical system (Intuitive Surgical) was approved as a medical
      device in 2009 by the Japanese Ministry of Health, Labour and Welfare. Robotic
      surgery has since been used in gastrointestinal, thoracic, gynecological, and
      urological surgeries. In April 2012, robotic-assisted laparoscopic radical
      prostatectomy (RALP) was first approved for insurance coverage. Since then, RALP
      has been increasingly used, with more than 3,000 RALP procedures performed by
      March 2013. By July 2014, 183 institutions in Japan had installed the da Vinci
      surgical system. Other types of robotic surgeries are not widespread because they
      are not covered by public health insurance. Clinical trials using robotic partial
      nephrectomy and robotic gastrectomy for renal and gastric cancers, respectively,
      have recently begun as advanced medical treatments to evaluate health insurance
      coverage. These procedures must be evaluated for efficacy and safety before being
      covered by public health insurance. Other types of robotic surgery are being
      evaluated in clinical studies. There are several challenges in robotic surgery,
      including accreditation, training, efficacy, and cost. The largest issue is the
      cost-benefit balance. In this review, the current situation and a prospective
      view of robotic surgery in Japan are discussed.

PMID- 25763121
TI  - Evolution of penile prosthetic devices.
AB  - Penile implant usage dates to the 16th century yet penile implants to treat
      erectile dysfunction did not occur until nearly four centuries later. The modern
      era of penile implants has progressed rapidly over the past 50 years as
      physicians' knowledge of effective materials for penile prostheses and surgical
      techniques has improved. Herein, we describe the history of penile prosthetics
      and the constant quest to improve the technology. Elements of the design from the
      first inflatable penile prosthesis by Scott and colleagues and the Small-Carrion
      malleable penile prosthesis are still found in present iterations of these
      devices. While there have been significant improvements in penile prosthesis
      design, the promise of an ideal prosthetic device remains elusive. As other
      erectile dysfunction therapies emerge, penile prostheses will have to continue to
      demonstrate a competitive advantage. A particular strength of penile prostheses
      is their efficacy regardless of etiology, thus allowing treatment of even the
      most refractory cases. 

PMID- 25763122
TI  - Structural modifications of the prostate in hypoxia, oxidative stress, and
      chronic ischemia.
AB  - PURPOSE: Clinical studies have reported a correlation between pelvic ischemia and
      voiding dysfunction in elderly men. The aim of this study was to identify and
      compare prostate structural modifications in cultured cells and in a rabbit model
      after exposure to hypoxia, oxidative stress, and chronic ischemia. MATERIALS AND
      METHODS: Cultured human prostate smooth muscle cells (SMCs), epithelial cells
      (ECs), and stromal cells (SCs) were incubated under normoxia, hypoxia, and
      oxidative stress conditions by use of a computerized oxycycler system. We
      developed a rabbit model of chronic prostate ischemia by creating aorto-iliac
      arterial atherosclerosis. Markers of oxidative stress were examined by using
      fluorometric analysis and enzyme immunoassay. Prostate structure was examined by
      using Masson's trichrome staining and transmission electron microscopy (TEM).
      RESULTS: Lipid peroxidation was found in SMCs exposed to hypoxia and in all cell
      types exposed to oxidative stress. We identified protein oxidation in ECs exposed
      to hypoxia and in all cell types exposed to oxidative stress. Markers indicating
      oxidative damage were present in chronically ischemic rabbit prostate tissue.
      These reactions were associated with DNA damage. Prostate ischemia resulted in
      epithelial atrophy, loss of smooth muscle, and diffuse fibrosis. TEM showed
      swollen mitochondria with degraded cristae, loss of membrane, loss of Golgi
      bodies, degenerated nerves, and disrupted cell-to-cell junctions. CONCLUSIONS:
      Human prostate cells exhibited differential reactions to hypoxia and oxidative
      stress with widespread DNA damage. Structural modifications in ischemic prostate
      tissue were similar to those in cells exposed to oxidative stress. Structural
      changes due to ischemia and oxidative stress may contribute to prostatic
      noncompliance in aging men.

PMID- 25763123
TI  - Optimizing in vivo gene transfer into mouse corpus cavernosum by use of surface
      electroporation.
AB  - PURPOSE: Electroporation is known to enhance the efficiency of gene transfer
      through a transient increase in cell membrane permeability. The aim of this study
      was to determine the optimal conditions for in vivo electroporation-mediated gene
      delivery into mouse corpus cavernosum. MATERIALS AND METHODS: Diabetes was
      induced in C57BL/6 mice by intraperitoneal injections of streptozotocin. After
      intracavernous injection of pCMV-Luc (100 ug/40 uL), different electroporation
      settings (5-50 V, 8-16 pulses with a duration of 40-100 ms) were applied to the
      penis to establish the optimal conditions for electroporation. Gene expression
      was evaluated by luciferase assay. We also assessed the undesired consequences of
      electroporation by visual inspection and hematoxylin-eosin staining of penile
      tissue. RESULTS: Electroporation profoundly induced gene expression in the corpus
      cavernosum tissue of normal mice in a voltage-dependent manner. We observed
      electrical burn scars in the penis of normal mice who received electroporation
      with eight 40-ms pulses at a voltage of 50 V and sixteen 40-ms pulses, eight 100
      ms pulses, and sixteen 100-ms pulses at a voltage of 30 V. No detectable burn
      scars were noted in normal mice stimulated with eight 40-ms pulses at a voltage
      of 30 V. Electroporation also significantly induced gene expression in diabetic
      mice stimulated with 40-ms pulse at a voltage of 30 V without injury to the
      penis. CONCLUSIONS: We have established the optimal electroporation conditions
      for maximizing gene transfer into the corpus cavernosum of mice while avoiding
      damage to the erectile tissue. The electroporation-mediated gene delivery
      technique will be a valuable tool for gene therapy in the field of erectile
      dysfunction.

PMID- 25763124
TI  - Interferon treatment for Japanese patients with favorable-risk metastatic renal
      cell carcinoma in the era of targeted therapy.
AB  - PURPOSE: Single-agent interferon (IFN) is no longer regarded as a standard option
      for first-line systemic treatment of metastatic renal cell carcinoma (RCC) in
      Western countries. However, some patients with favorable-risk RCC may still
      achieve complete and long-lasting remission in response to IFN treatment. The
      present study compared favorable-risk Japanese patients with metastatic RCC
      Japanese patients who had been treated with IFN or tyrosine kinase inhibitor
      (TKI) therapy as a first-line systemic therapy. MATERIALS AND METHODS: From 1995
      to 2014, a total of 48 patients with favorable risk as defined by the Memorial
      Sloan Kettering Cancer Center criteria who did not receive adjuvant systemic
      therapy were retrospectively enrolled in this study. We assessed the tumor
      response rate, progression-free survival (PFS), and overall survival (OS).
      RESULTS: The objective response rate for first-line therapy was 29% in the IFN
      group and 47% in the TKI group, but this difference did not reach the level of
      statistical significance. Median OS for IFN and TKI was 71 and 47 months,
      respectively (p=0.014). Median first-line PFS for IFN and TKI was 20 and 16
      months, respectively (no significant difference). First-line IFN therapy did not
      prove inferior to TKI therapy in terms of OS according to metastatic sites.
      CONCLUSIONS: IFN is associated with a survival benefit in Japanese patients with
      favorable-risk metastatic RCC in the era of targeted therapy. Further prospective
      study is needed.

PMID- 25763125
TI  - Clinicopathological features of Xp11.2 translocation renal cell carcinoma.
AB  - PURPOSE: Xp11.2 translocation renal cell carcinoma (RCC) is characterized by
      various translocations of the TFE3 transcription factor gene. These rare cancers
      occur predominantly in children and young adults. Here, we review the
      clinicopathological features of Xp11.2 translocation RCC. MATERIALS AND METHODS:
      We identified 21 patients with Xp11.2 translocation RCC. We retrospectively
      analyzed patient characteristics, clinical manifestations, and specific
      pathological features to assess definitive diagnosis, surgical and systemic
      treatments, and clinical outcomes. RESULTS: The mean age at diagnosis was 43.4+/
      20.0 years (range, 8-80 years; 8 males and 13 females). Eleven patients were
      incidentally diagnosed, nine patients presented with local symptoms, and one
      patient presented with systemic symptoms. The mean tumor size was 6.2+/-3.8 cm
      (range, 1.9-14 cm). At the time of diagnosis, 11, 1, and 5 patients showed stage
      I, II, and III, respectively. Four patients showed distant metastasis. At
      analysis, 15 patients were disease-free after a median follow-up period of 30.0
      months. Four patients received target therapy but not effectively. CONCLUSIONS:
      Xp11 translocation RCC tends to develop in young patients with lymph node
      metastasis. Targeted therapy did not effectively treat our patients. Surgery is
      the only effective therapy for Xp11 translocation RCC, and further studies are
      needed to assess systemic therapy and long-term prognosis.

PMID- 25763126
TI  - Efficacy and safety of holmium laser enucleation of the prostate for extremely
      large prostatic adenoma in patients with benign prostatic hyperplasia.
AB  - PURPOSE: To evaluate the efficacy and safety of holmium laser enucleation of the
      prostate (HoLEP) for extremely large prostates. MATERIALS AND METHODS: Patients
      undergoing HoLEP between July 2008 and December 2013 from the Seoul National
      University Hospital Benign Prostatic Hyperplasia Database Registry were
      retrospectively analyzed. The patients were divided into three groups according
      to their total prostate volume (TPV): group A (TPV<100 mL), group B (100
      mL<=TPV<200 mL), and group C (TPV>=200 mL); the clinical data of the three groups
      were compared. All patients were followed up 2 weeks, 3 months, and 6 months
      after surgery. RESULTS: A total of 502 patients (group A, 426; group B, 70; group
      C, 6) with a mean age of 69.0 (standard deviation, +/-7.3) years were included in
      our analysis. The mean prostate volume and prostate-specific antigen level were
      68.7+/-36.9 mL and 4.15+/-4.24 ng/mL, respectively. The enucleation and
      morcellation times were longer in group C (p<0.001), and the enucleation efficacy
      was higher in this group (p<0.001, R(2)=0.399). Moreover, the mean postoperative
      catheterization and hospitalization periods were significantly longer in group C
      (p=0.004 and p=0.011, respectively). However, there were no significant
      differences between the groups in any other postoperative events, including
      recatheterization, reoperation, urinary tract infection, clot retention, and
      bladder neck contracture (p range, 0.516-0.913). One patient in group C
      experienced recurrence of the urethral stricture. CONCLUSIONS: HoLEP in patients
      with an extremely large prostate can be performed efficiently and safely.

PMID- 25763127
TI  - A novel transurethral resection technique for superficial flat bladder tumor:
      grasp and bite technique.
AB  - PURPOSE: Transurethral resection of bladder tumor (TURBT) can be a challenging
      procedure for an inexperienced surgeon. We suggest an easy technique for TURBT,
      which we have named the "grasp and bite" technique. We describe this technique
      and compare its effectiveness and safety with that of conventional TURBT.
      MATERIALS AND METHODS: Monopolar TURBT (24-Fr Karl Storz) was performed in 35
      patients who had superficial bladder tumors. After defining the tumor margin, the
      tumor and surrounding mucosa were grasped by use of a loop electrode and
      resectoscope sheath. With tight grasping, linear moving resection was performed.
      The patients' demographic, intraoperative, and postoperative data were analyzed
      between the conventional and grasp and bite TURBT groups. RESULTS: Of 35
      patients, 16 patients underwent conventional TURBT (group 1), and the other 19
      patients underwent grasp and bite TURBT (group 2). Both groups were similar in
      age, tumor multiplicity, size, anesthesia method, and location. Grasp and bite
      TURBT could be performed as safely and effectively as conventional TURBT. There
      were no significant differences in irrigation duration, urethral catheterization,
      postoperative hemoglobin drop, or length of hospital stay. No significant side
      effects such as bladder perforation, severe obturator reflex, or persistent
      bleeding occurred. There were no significant pathological differences between
      specimens according to the type of resection technique. CONCLUSIONS: The grasp
      and bite TURBT technique was feasible for superficial bladder tumors. It may be a
      good tool for inexperienced surgeons owing to its convenient and easy manner.

PMID- 25763128
TI  - Comparative analysis of benign prostatic hyperplasia management by urologists and
      nonurologists: a Korean nationwide health insurance database study.
AB  - PURPOSE: To compare the current management of benign prostatic hyperplasia (BPH)
      by urologists and nonurologists by use of Korean nationwide health insurance
      data. MATERIALS AND METHODS: We obtained patient data from the national health
      insurance system. New patients diagnosed with BPH in 2009 were divided into two
      groups depending on whether they were diagnosed by a urologist (U group) or by a
      nonurologist (NU group). RESULTS: A total of 390,767 individuals were newly
      diagnosed with BPH in 2009. Of these, 240,907 patients (61.7%) were in the U
      group and 149,860 patients (38.3%) were in the NU group. The rate of all initial
      evaluation tests, except serum creatinine, was significantly lower in the NU
      group. The initial prescription rate was higher in the U group, whereas the
      prescription period was longer in the NU group. Regarding the initial drugs
      prescribed, the use of alpha-blockers was common in both groups. However, the U
      group was prescribed combination therapy of an alpha-blocker and 5-alpha
      reductase inhibitor as the second choice, whereas the NU group received
      monotherapy with a 5-alpha-reductase inhibitor. During the 1-year follow-up, the
      incidence of surgery was significantly different between the U group and the NU
      group. CONCLUSIONS: There are distinct differences in the diagnosis and treatment
      of BPH by urologists and nonurologists in Korea. These differences may have
      adverse consequences for BPH patients. Urological societies should take a
      leadership role in the management of BPH and play an educational role for
      nonurologists as well as urologists.

PMID- 25763129
TI  - Effect of weight reduction on the severity of lower urinary tract symptoms in
      obese male patients with benign prostatic hyperplasia: a randomized controlled
      trial.
AB  - PURPOSE: We assessed whether weight reduction is an effective intervention for
      the management of lower urinary tract symptoms (LUTS) and investigated the
      relationship between obesity and LUTS. MATERIALS AND METHODS: This was a
      prospective randomized controlled trial that enrolled obese men older than 50
      years with LUTS. The study period was 52 weeks. All patients received
      standardized alpha-adrenergic blocker therapy for the treatment of benign
      prostatic hyperplasia (BPH) during the run-in period. Patients were randomized to
      receive either a standardized prerecorded video program on the general principle
      of weight reduction or a comprehensive weight reduction program. Patients were
      assessed at different time points with symptom assessment, uroflowmetry,
      transrectal ultrasound, and metabolic assessment. RESULTS: Sixty-five patients
      were allocated to each study arm. After the study period, no significant
      difference in weight reduction was found between the two arms. When the pre- and
      postintervention parameters were compared, none were statistically different
      between the 2 arms, namely nocturia, International Prostate Symptom Score,
      quality of life assessment, and uroflowmetry parameters. When the whole study
      population was taken as a single cohort, these parameters were also not
      significantly different between the group with a body mass index of 25 to <30
      kg/m(2) and the group with a BMI of 30 to 35 kg/m(2). CONCLUSIONS: We found no
      association between obesity and LUTS. This could have been due to the less marked
      weight difference in our cohort. Whereas weight reduction may be an effective
      measure to improve LUTS, the implementation of a successful program remains a
      challenge.

PMID- 25763130
TI  - Penile length, digit length, and anogenital distance according to birth weight in
      newborn male infants.
AB  - PURPOSE: Anogential distance (AGD) and the 2:4 digit length ratio appear to
      provide a reliable guide to fetal androgen exposure. We intended to investigate
      the current status of penile size and the relationship between penile length and
      AGD or digit length according to birth weight in Korean newborn infants.
      MATERIALS AND METHODS: Between May 2013 and February 2014, among a total of 78
      newborn male infants, 55 infants were prospectively included in this study.
      Newborn male infants with a gestational age of 38 to 42 weeks and birth
      weight>2.5 kg were assigned to the NW group (n=24) and those with a gestational
      age<38 weeks and birth weight<2.5 kg were assigned to the LW group (n=31). Penile
      size and other variables were compared between the two groups. RESULTS: Stretched
      penile length of the NW group was 3.3 +/- 0.2 cm, which did not differ
      significantly from that reported in 1987. All parameters including height,
      weight, penile length, testicular size, AGD, and digit length were significantly
      lower in the LW group than in the NW group. However, there were no significant
      differences in AGD ratio or 2:4 digit length ratio between the two groups.
      CONCLUSIONS: The penile length of newborn infants has not changed over the last
      quarter century in Korea. With normal penile appearance, the AGD ratio and 2:4
      digit length ratio are consistent irrespective of birth weight, whereas AGD,
      digit length, and penile length are significantly smaller in newborns with low
      birth weight.

PMID- 25763131
TI  - Contemplating the Importance of Toll-like Receptors I and II Regarding Human
      Viral Pathogenesis.
AB  - BACKGROUND: Toll-like receptors (TLRs) play a major role in innate immunity,
      since they detect conserved pathogen-associated molecular patterns (PAMPs) on a
      range of microbes, including viruses, leading to innate immune activation and
      orchestration of the adaptive immune response. OBJECTIVES: The current study
      aimed to discuss earlier evidence implicating TLRs I and II in the innate immune
      response to viruses, in the light of more recent clinical data demonstrating that
      TLRs are important for anti-viral immunity in humans. MATERIALS AND METHODS: A
      literature search was performed via accessing research articles from PakMediNet,
      Pubmed and Google Scholar with key words of Toll-like receptors I and II
      Regarding human viral pathogenesis. The valued information on the recent
      scientific horizons was subjected to critical analysis. RESULTS: Comprehensive
      literature review illustrates important signaling pathways involved in TLR1/TLR2
      mediated regulation of viral pathogenesis. TLRs mediated activation of apoptosis
      tends to contribute towards defense strategies utilized by innate immune
      response. Activation of antiviral TLR1-dependent signaling cascade would
      ultimately lead to activation of NF-kappa B which promotes antiviral responses
      via induction of specific genes. TLR1/TLR2 dimer generates intracellular
      signaling via IRAK4 mediated activation of IRAK1/2 which results in activation of
      NF-kappa B, p38 and JNK proteins in cytoplasm. NF- kappa B, p38 and JNK enter the
      nucleus thereby causing activation of various pro-inflammatory cytokines such as
      IL-1 beta, TNF-alpha, IL-6, IL-8 and IL-18. Among the chronic HCV infection, the
      HCV core protein induces TNF-alpha and IL-10 from the macrophages thereby causing
      reduction in release of interferon alpha. Abnormal TLR1/TLR2 signaling may
      contribute to the enhancement of infection-related morbidity and mortality.
      CONCLUSIONS: To date, a large number of viruses are proved to trigger innate
      immunity via TLRs, suggesting that these receptors are likely to be important in
      the outcome of viral infection. This suggestion is supported by the observation
      that many viruses have evolved mechanisms not only to evade the innate immune
      system, but also to subvert it for the benefit of the virus.

PMID- 25763132
TI  - Chemical Compositions and Antimicrobial Activities of Ocimum sanctum L. Essential
      Oils at Different Harvest Stages.
AB  - BACKGROUND: Essential Oils (EOs) possess antibacterial properties and represent a
      natural source to treat infections and prevent food spoilage. Their chemical
      composition might be affected by the environmental condition and the
      developmental growth stages of the plant. OBJECTIVES: The current study aimed to
      determine the variations in chemical compositions and antimicrobial activities of
      the EOs of Ocimum sanctum L. at different stages of harvesting. MATERIALS AND
      METHODS: The oils constituents were analyzed by gas chromatography/mass
      spectrometry (GC/MS). The effects of three different harvest stages of O. sanctum
      EOs against most common causes of food-borne were evaluated by broth micro
      dilution method as recommended by the Clinical and Laboratory Standards Institute
      (CLSI). RESULTS: The analysis of the EOs indicated that eugenol was the major
      compound of the EOs at all developmental stages which reached its maximum level
      at the second stage. The results showed that the tested EOs exhibited
      antimicrobial activities against all of the examined pathogens at concentrations
      of 0.125-32 uL/mL, except Pseudomonas aeruginosa which was only inhibited by high
      concentrations of the floral budding and full flowering EOs. EO distilled from
      the second developmental growth stage (floral budding) of O. sanctum exhibited
      the strongest antibacterial activities against the food borne bacteria.
      CONCLUSIONS: Considering the wide range of antimicrobial activities of the
      examined EOs, they might have the potential to be used to manage infectious
      diseases or extend the shelf life of food products.

PMID- 25763133
TI  - Detection of Aspergillus flavus and A. fumigatus in Bronchoalveolar Lavage
      Specimens of Hematopoietic Stem Cell Transplants and Hematological Malignancies
      Patients by Real-Time Polymerase Chain Reaction, Nested PCR and Mycological
      Assays.
AB  - BACKGROUND: Pulmonary aspergillosis (PA) is one of the most serious complications
      in immunocompromised patients, in particular among hematopoietic stem cell
      transplants (HSCT) and patients with hematological malignancies. OBJECTIVES: The
      current study aimed to evaluate the incidence of PA and utility of molecular
      methods in HSCT and patients with hematological malignancies, four methods
      including direct examination, culture, nested polymerase chain reaction (PCR) and
      real-time PCR were performed on bronchoalveolar lavage (BAL) specimens in Tehran,
      Iran. PATIENTS AND METHODS: During 16 months, 46 BAL specimens were obtained from
      individuals with allogeneic HSCT (n = 18) and patients with hematological
      malignancies (n = 28). Direct wet mounts with 20% potassium hydroxide (KOH) and
      culture on mycological media were performed. The molecular detection of
      Aspergillus fumigatus and A. flavus was done by amplifying the conserved
      sequences of internal transcribed spacer 1 (ITS1) ribosomal DNA by nested-PCR and
      the beta-tubulin gene by TaqMan real-time PCR. RESULTS: Seven (15.2%) out of 46
      specimens were positive in direct examination and showed branched septate hyphae;
      11 (23.9%) had positive culture including eight (72.7%) A. flavus and three
      (27.3%) A. fumigatus; 22 (47.8%) had positive nested-PCR and eight (17.4%) had
      positive real-time PCR. The incidence of invasive pulmonary aspergillosis (IPA)
      in these patients included proven IPA in 1 (2.2%), probable IPA in 10 (21.7%),
      possible IPA in 19 (41.3%) and not IPA in 16 cases (34.8%). CONCLUSIONS: The
      incidence of IPA in allogeneic HSCT and patients with hematological malignancies
      was relatively high and A. flavus was the most common cause of PA. As molecular
      methods had higher sensitivity, it may be useful as screening methods in HSCT and
      patients with hematological malignancies, or to determine when empirical
      antifungal therapy can be withheld.

PMID- 25763134
TI  - Oral amoxicillin-clavulanic Acid treatment in urinary tract infections caused by
      extended-spectrum Beta-lactamase-producing organisms.
AB  - BACKGROUND: Extended-spectrum beta-lactamases (ESBLs) are increasing problems.
      The involvement of ESBL-producing organisms is associated with higher rates of
      carbapenem usage in urinary tract infections (UTIs). Though some strains are
      susceptible to amoxicillin-clavulanic acid (AMC) in vitro, there is very less
      data about the consequences of AMC usage for such infections. OBJECTIVES: The
      purpose of this study was to evaluate the clinical and microbiological outcomes
      of AMC treatment in UTIs caused by AMC-susceptible ESBL-producing organisms.
      PATIENTS AND METHODS: A retrospective cohort study was conducted in a tertiary
      care hospital. Forty-six out of 652 patients (F/M ratio: 32/14; mean age: 43.9
      years) with ESBL-positive UTIs were eligible for this study. These patients had
      cystitis (n = 23), vesicoureteral reflux (n = 7), hyperactive bladder (n = 6),
      and prostatitis (n = 10). Data was collected via chart review and was
      statistically analyzed. RESULTS: AMC-susceptible ESBL-producing Escherichia coli,
      Klebsiella pneumoniae and K. oxytoca were identified as the causative agents in
      31, 14, and 1 patients, respectively. Thirty-nine (84.7%) out of 46 patients were
      successfully treated with oral AMC. Additionally, 2 (4.3%) patients' urine
      cultures turned to be negative, though their clinical complaints and leukocyturia
      had continued. In the remaining 5 (10.8%) patients, no positive clinical and
      microbiological response was obtained. Increased minimum inhibitory concentration
      levels of AMC (from 4 to > 256 ug/mL) were detected in these patients and the
      treatment failures were attributed to this developing resistance. We found that
      therapeutic failure was significantly more frequent in Klebsiella spp. than in E.
      coli (33.3% vs 6.5%, P = 0.029). Furthermore, no treatment failure was observed
      in pathogens with minimum inhibitory concentrations (MICs) <= 2 mg/mL, and the
      high AMC MIC (8 mg/mL) was associated with resistance development and therapeutic
      failure (71.4% vs. 5.1%, P = 0.0001). CONCLUSIONS: Our results suggested that
      amoxicillin-clavulanic acid may be a good oral antimicrobial which can be used
      for treatment of ESBL-positive UTIs, if the causative agent is susceptible to
      this antibiotic. However, some strains may develop resistance during therapy,
      especially in those exhibiting high AMC MICs.

PMID- 25763135
TI  - Prevalence, plasmids and antibiotic resistance correlation of enteric bacteria in
      different drinking water resources in sohag, egypt.
AB  - BACKGROUND: One of the major health causing problems is contamination of drinking
      water sources with human pathogenic bacteria. Enteric bacteria such as Shigella,
      Salmonella and Escherichia coli are most enteric bacteria causing serious health
      problems. Occurrence of such bacteria infection, which may resist antibiotics,
      increases the seriousness of problem. OBJECTIVES: The aim of this study was to
      examine the prevalence of some enteric bacteria (Shigella, Salmonella and E.
      coli) in addition to Pseudomonas. The antibiotic susceptibility of these bacteria
      was also tested, in addition to assessing plasmid(s) roles in supposed
      resistance. MRSA genes in non-staphylococci were clarified. MATERIALS AND
      METHODS: Water samples were collected from different drinking sources (Nile,
      ground water) and treated tap water. Selective media were used to isolate enteric
      bacteria and Pseudomonas. These bacteria were identified, counted and examined
      for its susceptibility against 10 antibiotics. The plasmids were screened in
      these strains. MRSA genes were also examined using PCR. RESULTS: Thirty-two
      bacterial strains were isolated from Nile and ground water and identified as S.
      flexneri, S. sonnei, S. serovar Newport, Pseudomonas aeruginosa and E. coli
      strains according to standard methods. According to antibiotic susceptibility
      test, 81% of strains were resistant to Cefepime, whereas 93.75% were sensitive to
      Ciprofloxacin. Correlation analysis between plasmids profiles and antibiotics
      sensitivities showed that 50% of the total strains had plasmids. These strains
      showed resistance to 50% of the used antibiotics (as average value); whereas, the
      plasmids free strains (50%) were resistant to 48.7% of the antibiotics. No
      distinct correlation between plasmids and antibiotic resistance in some strains
      could be concluded in this study. No MRSA gene was detected among these non
      staphylococci strains. No bacteria were isolated from treated tap water.
      CONCLUSIONS: Thirty-three bacterial strains; 10 strains of E. coli, 10 strains of
      S. flexneri, 3 strains S. sonnei, 2 strains of S. serovar Newport, and 7 strains
      of P. aeruginosa, were isolated and identified from Nile water and ground water
      in Sohag governorate. The prevalence of enteric bacteria in water sources in
      studying area was considerable. No clear or distinct correlation could be
      concluded between plasmids and antibiotic resistance. No MRSA gene was detected
      in these non-staphylococci strains, and no pathogenic bacteria were isolated from
      treated tap water. The hygiene procedures in the studying area seem to be
      adequate, despite the failure to maintain water sources form sewage pollution.

PMID- 25763136
TI  - Correlation and variation-based method for identifying reference genes from large
      datasets.
AB  - BACKGROUND: Reference genes are assumed to be stably expressed under most
      circumstances. Previous studies have shown that identification of potential
      reference genes using common algorithms, such as NormFinder, geNorm, and
      BestKeeper, are not suitable for microarray-sized datasets. The aim of this study
      was to evaluate existing methods and develop methods for identifying reference
      genes from microarray datasets. METHODS: We evaluated the correlation between
      outputs from 7 published methods for identifying reference genes, including
      NormFinder, geNorm, and BestKeeper, using subsets of published microarray data.
      From these results, seven novel combinations of published methods for identifying
      reference genes were evaluated. RESULTS: Our results showed that NormFinder's and
      geNorm's indices had high correlations (R(2) = 0.987, P < 0.0001), which is
      consistent with the findings of previous studies. However, NormFinder's and
      BestKeeper's indices (R(2) = 0.489, 0.01 < P < 0.05) and NormFinder's coefficient
      of variance (CV) suggested a lower correlation (R(2) = 0.483, 0.01 < P < 0.05).
      We developed two novel methods with high correlations with NormFinder (R(2)
      values of both methods were 0.796, P < 0.0001). In addition, computational times
      required by the two novel methods were linear with the size of the dataset.
      CONCLUSION: Our findings suggested that both of our novel methods can be used as
      alternatives to NormFinder, geNorm, and BestKeeper for identifying reference
      genes from large datasets. These methods were implemented as a tool,
      OLIgonucleotide Variable Expression Ranker (OLIVER), which can be downloaded from
      http://sourceforge.net/projects/bactome/files/OLIVER/OLIVER_1.zip.

PMID- 25763137
TI  - Bony manifestation of rickets in a sunny city - a case report from Yazd, Iran.
AB  - Rickets is disease that occurs in growing bones in which defective mineralization
      occurs in both the bone and the cartilage of the epiphyseal growth plate,
      resulting in the retardation of growth and skeletal deformities. Rickets is more
      common in areas with less sunlight. However, this case report presents a case of
      the bony manifestation of rickets with the intake of vitamin D supplements in
      Yazd, a city in central Iran that has sunshine almost every day. A patient was
      referred to an out-patient general pediatric clinic for deformities of the legs
      and growth disturbance, with his height far below the normal range. The changes
      that were most evident in his X-rays were the bowing of the long bones of the
      legs and forearms and the cupping of the wrist metaphyseal region. In summary, we
      present a patient with bony manifestation of rickets despite living in a sunny
      area and taking vitamin D supplements. Thus, it is important to remember that
      rickets is still a common disease among children in Iran. More studies of this
      issue should be conducted, including the identification of abnormal cases and
      rescheduling vitamin D supplementation programs. 

PMID- 25763138
TI  - Prevalence of smoking in northwest Iran: a meta-analysis.
AB  - BACKGROUND: Tobacco addiction is a major cause of preventable death worldwide.
      Thus, efforts to eliminate its use have the potential of producing significant
      health benefits. The purpose of this study was to conduct a meta-analysis to
      estimate the prevalence of cigarette smoking among people in the age range of 15
      to 64. The specific objective of this meta-analysis was to provide valid data
      that policy makers can use to make evidence-based decisions. METHODS: To
      determine the prevalence of smoking among the adult population in northwest Iran,
      we used reports published by the surveillance system used to assess the risk
      factors for non-communicable diseases in different provinces in northwest Iran
      for the years 2004 and 2006-2009. Several variables were extracted, including the
      years of study, gender, ages, and smoking prevalence. Based on the heterogeneity
      of the results, we used fixed or random effects models to estimate the overall
      prevalence of cigarette smoking. The analyses were performed using Stata 11
      software. RESULTS: A total of 28,436 subjects (14,248 males and 14,188 females)
      in five age groups, i.e., 15-24, 25-34, 35-44, 45-54, and 55-64, were
      interviewed. Meta-analysis in men showed that, across the age groups, the lowest
      prevalence was 22.9%, the highest prevalence was 26.5%, and the average
      prevalence was 24.7%. Among women, the lowest prevalence was 0.3%, the highest
      prevalence was 0.8%, and the average prevalence was 0.5%. CONCLUSION: We found
      that approximately one-fourth of males in the age range of 15-64 in northwest
      Iran smoked cigarettes daily. Therefore, it is necessary to conduct effective
      interventions to reduce the prevalence of addiction to tobacco in this area.

PMID- 25763139
TI  - A comparative study of the classic and piggyback techniques for orthotopic liver
      transplantation.
AB  - BACKGROUND: The classic technique of hepatectomy with venovenous bypass may cause
      a longer anhepatic phase and increase the rate of some complications, such as
      post-operative renal failure and thromboembolic events. But, in some cases, such
      as tumors and anatomic difficulties, the surgeon is obligated to use the classic
      technique even though there is some controversy about the safety of this
      technique without venovenous bypass in liver transplantation. The aim of this
      study was to compare the results of using the classic technique without
      venovenous bypass and the piggyback technique for liver transplantation. METHODS:
      A retrospective case-series study was conducted on 227 consecutive successful
      liver transplants, including 55 cases in which the classic technique was used and
      172 cases in which the piggyback technique was used. The transplants were
      performed from March 2010 through June 2011 in the Visceral Transplantation Ward
      at Namazi Hospital in Shiraz, Iran. The piggyback method was the preferred
      approach for hepatectomy, but the classic technique without venovenous bypass was
      performed in cirrhotic cases with anatomic difficulties, when there was a tumor,
      or when the surgeon preferred it. RESULTS: There were no significant differences
      in post-operative rise in creatinine, decreases in intraoperative blood pressure,
      transfused packed red blood cells (RBC), or survival rates between the groups.
      Warm ischemic time (duration that donor liver is out of ice until it's blood
      reperfusion in the recipient) was approximately seven minutes longer in the
      classic group (P = 0), but it was less than 52 minutes, which is an acceptable
      time for this phase. Hospital stays were shorter in the classic group than in the
      piggyback group (P = 0.024). CONCLUSION: Although the piggyback technique is the
      preferred technique for hepatectomy in liver transplantation, the classic
      technique without venovenous bypass can be used safely in cirrhotic livers when
      necessary or if the physician prefers it.

PMID- 25763140
TI  - A survey of the quality of nursing services for brain trauma patients in the
      emergency wards of hospitals in Guilan Province, Iran (2012).
AB  - BACKGROUND: Head trauma is the main cause of disabilities and death among young
      people, and the side effects of head trauma pose some of the greatest medical
      challenges. Rapid diagnosis and the use of proper treatments can prevent more
      severe brain damage. The purpose of this research was to determine the quality of
      nursing services provided to brain trauma patients in hospitals in Guilan
      Province, Iran. METHODS: The study was conducted as a descriptive, cross
      sectional study in the emergency wards of selected hospitals in Guilan in 2012.
      The research population was comprised of all the brain trauma patients in these
      hospitals. We developed a two-section questionnaire, ascertained its validity,
      and determined that it had a reliability of 88% (Cronbach's alpha). Subsequently,
      we used the questionnaire for gathering data. The data were analyzed using SPSS
      statistical software, and descriptive analysis tests (frequency rate and average)
      and deductive analyses tests (chi-squared) also were used. RESULTS: The results
      showed that the quality of health services provided to brain-trauma patients in
      the emergency ward was at the moderate level of 58.8% of the cases and at a low
      level in 41.2% of the cases. CONCLUSION: Based on the results that showed that
      the services were of moderate quality, the staff members in the emergency ward
      were required to update their knowledge and use the required measures to minimize
      or prevent side effects in brain-trauma patients; clearly, mastery of such
      measures was a real need among the emergency ward's staff.

PMID- 25763141
TI  - Survey of accidents in suburban Tehran and the prediction of future events based
      on a time-series model.
AB  - BACKGROUND: Car accidents are currently a social issue globally because they
      result in the deaths of many people. The aim of this study was to examine traffic
      accidents in suburban Tehran and forecast the number of future accidents using a
      time-series model. METHODS: The sample population of this cross-sectional study
      was all traffic accidents that caused death and physical injuries in suburban
      Tehran in 2010 and 2011, as registered by the Tehran Emergency Section. In the
      present study, Minitab 15 software was used to provide a description of traffic
      accidents in suburban Tehran for the specified time period as well as those that
      occurred during April 2012. RESULTS: The results indicated that the average
      number of traffic accidents in suburban Tehran per day in 2010 was 7.91 with a
      standard deviation of 7.70. This figure for 2011 was 6 daily traffic accidents
      with a standard deviation of 5.30. A one-way analysis of variance indicated that
      the average of traffic accidents in suburban Tehran was different for different
      months of the year (P = 0.000). The study results showed that different seasons
      in 2010 and 2011 had significantly different numbers of traffic accidents (P <
      0.05). Through an auto-regressive moving average (ARMA), it was predicted that
      there would be 166 traffic accidents in April 2012 with a mean of 5.53 and
      maximum of 6 traffic accidents/day. CONCLUSION: There has been a decreasing trend
      in the average number of traffic accidents per day.

PMID- 25763142
TI  - Life Satisfaction in children and adolescents with beta thalassemia major in
      southwest Iran.
AB  - BACKGROUND: Beta thalassemia major has a considerable impact on quality of life.
      The purpose of this study was to determine the life satisfaction of beta
      thalassemic children and adolescents compared to healthy controls. METHODS: This
      research, conducted in 2009, was a controlled, cross-sectional study in which
      beta-thalassemic patients, who were being followed-up by the Thalassemic Center
      in Bushehr, a city in southern Iran, were compared with a healthy control group.
      The Multi-dimensional Student Life Satisfaction Scale (MSLSS) was used to measure
      the participants' quality of life in five domains. The chi-squared test, t-test,
      Pearson's Product Moment Correlation, and multiple regression analysis were used
      for the statistical analyses. RESULTS: The unadjusted mean scores of three of the
      domains, i.e., school, friends, and living environment, and the total score of
      five domains, i.e., school, friends, living environment, family, and self, were
      significantly higher in thalassemic patients than in the control group (P <
      0.05). These significant differences were persistent after adjusting the mean
      scores of the three domains and the total score of the five domains for age,
      gender, and educational level. CONCLUSION: The thalassemic patients were more
      satisfied with life than the healthy controls in Bushehr. Many factors may be
      responsible for this finding. The results of this study suggest that the attitude
      of parents and society concerning assigning responsibility to patients should be
      assessed. The assessment should include comparing the satisfaction with life of
      thalassemic patients with that of their healthy siblings and conducting national
      studies on the quality of life of thalassemic patients and their satisfaction
      with life.

PMID- 25763143
TI  - Effect of executive programs of infection control committees on the prevalence of
      nosocomial infections in Kermanshah's Hospitals (2010-2011).
AB  - The aim of this study was to investigate the effect of executive programs of
      infection control committees on the incidence of nosocomial infections in
      hospitals affiliated with the Kermanshah University of Medical Sciences
      (Kermanshah, Iran) during 2010 and 2011. The numbers of patients admitted in 2010
      and 2011 were 8084 and 7166, respectively, and the average prevalence of
      nosocomial infections in 2010 and 2011 was 0.8 and 1.9 infections per 100
      patients, respectively. In 2010, the mean scores obtained by hospital for regular
      Infection Control Committee meetings, regular gatherings, registration of program
      information analysis, and regular follow-up meetings were 19, 31, 30.5, and 41.7
      (out of 100), respectively. In 2011, they were 20.2, 36.4, 38.1, and 50,
      respectively. The results of this study indicated that executive programs of
      infection control committees had no effect on the incidence of nosocomial
      infections; therefore, the experts who assess hospitals should pay more attention
      to the systems that are used to conduct surveillance of nosocomial infection
      control programs. 

PMID- 25763144
TI  - Contributing factors of obesity among stressed adolescents.
AB  - BACKGROUND: Many adolescents suffer from common mental disorders such as stress,
      which affects health through the psychosocial process, eating behavior, food
      choices and physical activity. During adolescence, dietary patterns are formed
      and can affect the occurrence of diseases in later life. This is a review of the
      results in the pertinent literature, from 1989 until November 2013, concerning
      stress and the contributing factors that lead to obesity among adolescents. The
      aim of this review is to identify obesity among stressed adolescents as well as
      the contributing factors. METHODS: A descriptive design was used for both
      quantitative and qualitative studies while, in addition, psychological theories
      were used for the qualitative studies. The articles were screened to ensure their
      quality and included in this review accordingly. Ten articles were included in
      the review comprising cross-sectional, cohort, review and meta-analysis.
      Interviews and questionnaires were used for data collection. RESULTS: The
      literature provided obvious information focusing on emotional stress and obesity
      for both boys and girls. This review revealed that stress results in overweight
      and obesity among adolescents through changes in lifestyle including decreased
      physical activity and increased food intake. Gender and economic status are the
      main components that affect obesity in stressed adolescents. CONCLUSION: Obesity
      is a consequence of stress among adolescents and is exacerbated by the wrong
      eating attitude. Developing proper food choices among adolescents can help
      prevent obesity and other complications in adulthood.

PMID- 25763145
TI  - Use of the Finnish method to quantify the ergonomic properties in an office
      environment among the workplaces in an Electricity Distribution Company in West
      Tehran Province.
AB  - BACKGROUND: The workplace plays an important role in workers' performances, but
      most workplaces have not been designed and equipped in keeping with primary
      ergonomic principles. Ignoring these principles can cause ergonomic risk factors,
      difficulties for workers, and damage to workers' health. The aim of this study
      was to identify acceptable ergonomic properties in workplaces in order to
      determine and investigate the aspects of workstations that cause occupational
      discomfort. To accomplish this aim, we used the Finish method to evaluate
      workstations in an electricity distribution company in Tehran. METHODS: This
      cross sectional study was conducted for all of the workstations in an electrical
      power distribution company using the census method. The desired information was
      collected through objective observation using the Finish checklist of ergonomic
      issues in the workplace. Then, we used SPSS version 16 to analyze the
      information. RESULTS: In 11.2% of the workstations, none of the ergonomic
      principles was considered, so workers' bodied were not situated appropriately
      while they were working. In 31% of the cases, lighting ranged between 10% and 50%
      of the recommended amount, and some of the workers appeared to be in a slight
      daze. In 42.3% of the cases, the temperature in the workplace was in the range of
      25 to 27 degrees C. In 42.3 and 52.3% of the cases, ratings of noise were 2 and
      3, respectively, indicating that the noise levels were 60-70 dB and 70-80 dB,
      respectively. CONCLUSION: The findings of this study can be used to determine
      ergonomic deficiencies in workstations so they can be resolved. Based on our
      investigation, it was found that the workstations, first and foremost, had
      significant defects in terms of work components. Furthermore, there were some
      irritating problems concerning noise and concerning comfort levels related to the
      high temperature.

PMID- 25763146
TI  - Why publish a medical case report?

PMID- 25763147
TI  - Unusual presentation of a perforated appendicitis in a four-year-old girl - a
      case report from Yazd, Iran.
AB  - Difficulties in the early diagnosis of appendicitis, particularly in children,
      often lead to complications, such as perforation of the appendix, within 36 hours
      of the onset of symptoms. A four-year-old girl presented to the Emergency
      Department at Shohadaye Kargar Hospital in Yazd (a city in central Iran) in
      February 2013 with a history of chronic abdominal pain that began 20 days before
      admission. Her physical examination revealed a low-grade fever, conjunctivitis,
      dysuria with malodorous urine, and a mass in right, lower quadrant without
      localized tenderness in that area. Intestinal intussusception was suggested as
      the most likely diagnosis, and a laparotomy was performed. The appendix was
      perforated and an appendicular abscess had caused intestinal obstruction. The
      rarity of this case, with its unusual presentation and findings, which included
      unexplained chronic pain, necessitated an immediate operation that revealed the
      acute presentation of a mechanical obstruction of the intestine. Appendicitis
      must be kept in the differential diagnosis of any child who presents with chronic
      abdominal pain. In conclusion, chronic abdominal pain in children is not always
      of functional origin, and discerning the correct diagnosis can be very
      challenging. Therefore, clinicians should think broadly since multi-disciplinary
      input may be inevitable. 

PMID- 25763148
TI  - Hospitals' readiness for clinical governance implementation in educational
      hospitals of yazd, iran.
AB  - BACKGROUND: Clinical governance is a systematic approach to maintaining and
      improving the quality of patient care. This study aimed to assess some Iranian
      educational hospitals' readiness for clinical governance implementation through
      the organizational climate. METHODS: It was a cross-sectional study that used the
      Clinical Governance Climate Questionnaire (CGCQ) in three educational hospitals
      in Yazd, a city in central Iran, in 2012. A total of 186 personnel contributed to
      the study. Data were analyzed using SPSS version 16. Descriptive statistics and
      the Kruskal-Wallis test were used for data analyses. RESULTS: The mean scores of
      the clinical governance climate in Shahid Sadoughi, Shahid Rahnemoon and Afshar
      hospitals were 2.63+/-0.29, 2.58+/-0.32, and 2.68+/-0.29. The mean scores of
      quality improvement planning and change, quality improvement integration and
      motivation, clinical risk management and climate of blame and punishment,
      organizational learning, and training and development (T&D) opportunities for
      learning in the studied hospitals were 2.21+/-0.49, 2.80+/-0.40, 2.76+/-0.40,
      2.91+/-0.54 and 3.06+/-0.72, respectively. CONCLUSION: The results of this study
      showed that the educational hospitals' climate should be more supportive for
      successful implementation of clinical governance.

PMID- 25763149
TI  - Morbidity patterns, nutritional status, and healthcare-seeking behavior of female
      garment workers in Bangladesh.
AB  - BACKGROUND: The ready-made garment (RMG) sector is the main pillar of
      Bangladesh's economy, and female garment workers are the key workers in this
      sector. Unfortunately, they are paid very little; in fact, their pay is among the
      lowest anywhere in the world. This situation makes the workers very vulnerable to
      different kinds of health-related problems, including malnutrition, and it also
      results in their having poor healthcare-seeking behavior. So, the aim of this
      study was to determine their nutritional status, their various kinds of health
      related problems, and their healthcare-seeking behavior. METHODS: This was a
      cross-sectional study in which purposive sampling was done. Data were collected
      through a structured questionnaire, and the participants' heights and weights
      were measured according the guidelines provided by the World Health Organization
      (WHO). All data were computed and analyzed using SPSS version 16.01 software. Chi
      squared values were calculated to analyze the data and the prevalence rate ratio
      (PRR) was measured to determine the association of body mass index (BMI) with
      health problems. RESULTS: More than half of the participants (53.67%) had various
      health problems, and almost half of them (43.33%) were underweight (BMI <= 18.5
      kg/m(2)). Among those who were underweight, about 96% of them had one or more
      health-related problems in the last three months (P-value < 0.001). Their PRR was
      2.59, which comprises low BMI as a risk factor for high morbidity. Among the
      workers who had one or more health-related problems, more than 22% of them did
      not go to see a doctor during their illnesses. Only about 12% of them went to
      qualified practitioners, and, surprisingly, 37% of those completed the prescribed
      treatment. CONCLUSION: The study showed that there is high morbidity among female
      garment workers who have low BMI values and poor healthcare-seeking behavior,
      factors that should be addressed by their employers and policy makers.

PMID- 25763150
TI  - NF-E2-related factor 2 over-expression in mesenchymal stem cells to improve
      cellular cardiomyoplasty.
AB  - Myocardial infarction (MI) is the leading cause of death worldwide. Various
      therapeutic strategies have been introduced for MI treatment. In recent years,
      interest in utilizing mesenchymal stem cells (MSCs) for MI therapy has increased.
      In fact, the use of MSCs for MI treatment, known as cellular cardiomyoplasty, is
      in the clinical trial stage. However, despite promising results, most MSCs die
      after transplantation as a result of exposure to various stresses. Nuclear factor
      (erythroid-derived 2)-like 2 (Nrf2), a well-known cytoprotective transcription
      factor, protects MSCs against some stresses. Over-expression of Nrf2 in MSCs
      decreases their apoptosis in vitro without any adverse effects on their
      differentiation capacity. Therefore, we hypothesized that over-expression of Nrf2
      in MSCs can improve cellular cardiomyoplasty. 

PMID- 25763151
TI  - Citation frequency and ethical issue.

PMID- 25763152
TI  - Optimization of Vertical Double-Diffused Metal-Oxide Semiconductor (VDMOS) Power
      Transistor Structure for Use in High Frequencies and Medical Devices.
AB  - Power transistors, such as the vertical, double-diffused, metal-oxide
      semiconductor (VDMOS), are used extensively in the amplifier circuits of medical
      devices. The aim of this research was to construct a VDMOS power transistor with
      an optimized structure to enhance the operation of medical devices. First, boron
      was implanted in silicon by implanting unclamped inductive switching (UIS) and a
      Faraday shield. The Faraday shield was implanted in order to replace the gate
      field parasitic capacitor on the entry part of the device. Also, implanting the
      UIS was used in order to decrease the effect of parasitic bipolar junction
      transistor (BJT) of the VDMOS power transistor. The research tool used in this
      study was Silvaco software. By decreasing the transistor entry resistance in the
      optimized VDMOS structure, power losses and noise at the entry of the transistor
      were decreased, and, by increasing the breakdown voltage, the lifetime of the
      VDMOS transistor lifetime was increased, which resulted in increasing drain flow
      and decreasing Ron. This consequently resulted in enhancing the operation of high
      frequency medical devices that use transistors, such as Radio Frequency (RF) and
      electrocardiograph machines. 

PMID- 25763153
TI  - Analysis of electrical accidents and the related causes involving citizens who
      are served by the Western of Tehran.
AB  - BACKGROUND: Electrical burns account for a significant percentage of fatal
      accidents. Each year, a number of consumers in Iran suffer from electrical
      injuries due to technical problems, equipment failures, and the unauthorized use
      of electricity. The aim of this study was to examine the root causes of accidents
      that involved electricity in the district served by the Western Tehran Province
      Electricity Distribution Company. METHODS: This was a descriptive study in which
      incidents involving electricity-related injuries were investigated among
      customers served by the Western Tehran Province Electricity Distribution Company.
      Therefore, we collected and analyzed incident reports filed by citizens from 2005
      through the first half of 2009 in the Distribution Company's coverage area,
      including Savejbolagh, Shahriyar, eastern Karaj, Qods City, southern Karaj,
      western Karaj, Malard, and Mehrshahr. The reported events were analyzed using
      SPSS software. RESULTS: Exposure of electricity lines and unauthorized
      construction of residential houses in areas where there were medium- and low
      voltage lines were responsible for 37% of the injuries. The findings showed that
      the highest rate of accidents occurred in 2008 and the first half of 2009. The
      highest rate of accidents occurred among people with a mean age of 35.
      CONCLUSION: The results from investigating the causes of electrical accidents
      emphasized the necessity of developing a culture of safety in communities,
      especially among employees who are engaged in occupations related to electricity,
      construction workers, and school children to reduce the rate of such accidents.

PMID- 25763154
TI  - Examining fatigue and insomnia symptoms among workers of a gas transmission
      industry in 2013.
AB  - BACKGROUND: Fatigue, which interferes with one's physical and mental operation,
      resulting in strength reduction and weakness, is considered one of the most
      important issues in the workplace. In addition, it can cause diseases,
      occupational accidents, and a reduction in an individual's efficiency. The
      aforementioned effects can be aggravated by fatigue in shift workers who
      experience sleep disturbance. The aim of this study was to investigate fatigue
      and the Insomnia Severity Index (ISI) among workers of a gas transmission
      industry in 2013. METHODS: This descriptive analytical study was conducted among
      300 workers of the aforementioned industry and required data was collected via
      the face-to-face survey method and questionnaires. Data analysis was done with
      the following techniques: Mann-Whitney, variance analysis test, independent t
      test, Kruskal-Wallis, Spearman's correlation test, and chi square test. RESULTS:
      The highest fatigue scores among fixed-dayshift and rotating-shift workers were 6
      and 7, respectively, and the fatigue level for both groups was 4. The average of
      all symptoms associated with fatigue and the total score on the Insomnia Severity
      Index in rotating-shift workers were higher than for dayshift workers and there
      was a significant difference between them (P=0.001). Lack of concentration,
      exhaustion, and fatigue during work were the most common symptoms of fatigue
      among the aforementioned shift workers in this evaluation. CONCLUSION: The
      findings indicated that the level of fatigue and severity of insomnia among
      workers of this gas transmission industry is very high. Since this can lead to
      occupational accidents and efficiency reduction, it is necessary to provide
      workers with opportunities such as short breaks during working hours, rest and
      exercise during work, paying adequate attention to the workers' human needs, and
      improving work systems.

PMID- 25763155
TI  - Comparing the Precision of Information Retrieval of MeSH-Controlled Vocabulary
      Search Method and a Visual Method in the Medline Medical Database.
AB  - BACKGROUND: Medline is one of the most important databases in the biomedical
      field. One of the most important hosts for Medline is Elton B. Stephens CO.
      (EBSCO), which has presented different search methods that can be used based on
      the needs of the users. Visual search and MeSH-controlled search methods are
      among the most common methods. The goal of this research was to compare the
      precision of the retrieved sources in the EBSCO Medline base using MeSH
      controlled and visual search methods. METHODS: This research was a semi-empirical
      study. By holding training workshops, 70 students of higher education in
      different educational departments of Kashan University of Medical Sciences were
      taught MeSH-Controlled and visual search methods in 2012. Then, the precision of
      300 searches made by these students was calculated based on Best Precision,
      Useful Precision, and Objective Precision formulas and analyzed in SPSS software
      using the independent sample T Test, and three precisions obtained with the three
      precision formulas were studied for the two search methods. RESULTS: The mean
      precision of the visual method was greater than that of the MeSH-Controlled
      search for all three types of precision, i.e. Best Precision, Useful Precision,
      and Objective Precision, and their mean precisions were significantly different
      (P <0.001). Sixty-five percent of the researchers indicated that, although the
      visual method was better than the controlled method, the control of keywords in
      the controlled method resulted in finding more proper keywords for the searches.
      Fifty-three percent of the participants in the research also mentioned that the
      use of the combination of the two methods produced better results. CONCLUSION:
      For users, it is more appropriate to use a natural, language-based method, such
      as the visual method, in the EBSCO Medline host than to use the controlled
      method, which requires users to use special keywords. The potential reason for
      their preference was that the visual method allowed them more freedom of action.

PMID- 25763156
TI  - Relationship between Organizational Perceived Justice and Organizational
      Citizenship Behavior among an Iranian Hospital's Employees, 2013.
AB  - BACKGROUND: Organizational citizenship behavior just referred to a set of
      discretionary workplace behaviors that exceed one's job requirements. The main
      objective of this study was to determine the relationship between organizational
      perceived justice and organizational citizenship behavior. METHODS: This cross
      sectional study was done in Shahid Sadoughi Hospital in Yazd, Iran in 2013. A
      total of 100 hospital employees contributed in the study. The required data was
      gathered using 2 valid questionnaires, including the Moorman & Niehoff
      organizational perceived justice questionnaire and the McKinsey organizational
      citizenship behavior questionnaire. Data were analyzed using SPSS version 16.
      Descriptive statistics, Chi square, and Pearson's correlation coefficient were
      used for data analysis. RESULTS: There was a significant positive relationship
      between organizational perceived justice and organizational citizenship behavior
      among the studied hospital's employees (P <= 0.05, R = 0.33). CONCLUSION: This
      study confirmed that any policy that leads to better organizational justice
      perception will contribute in better organizational citizenship behavior which
      will increase the hospital's productivity.

PMID- 25763157
TI  - The design and development of a computer game on insulin injection.
AB  - BACKGROUND: Insulin therapy is of high importance in glycemic control and
      prevention of complications in type 1 diabetes in children. However, this
      treatment is unpleasant and stressful for many children, and it is difficult for
      them to accept. The purpose of the study was to design and develop an educational
      computer game for diabetic children to familiarize them with insulin injections.
      METHODS: After a review of the literature and the collection of basic
      information, we discussed the purpose of this research with some diabetic
      children, their parents, and nurses. The findings that we acquired from the
      discussion were considered in designing and developing the game. Then, following
      the principles associated with the development of computer games, we developed
      seven different games that related to insulin injections, and the games were
      evaluated in a pilot study. RESULTS: The games developed through the design and
      programming environment of Adobe Flash Player and stored on a computer disk (CD).
      The seven games were a pairs game, a puzzle game, a question and answer game, an
      insulin kit game, a drawing room game, a story game, and an insulin injection
      room game). The idea was that diabetic children could become acquainted with
      insulin injections and the injection toolkit by playing a variety of entertaining
      and fun games. They also learned about some of the issues associated with insulin
      and experienced insulin injection in a simulated environment. CONCLUSIONS: It
      seems that the use of new technologies, such as computer games, can influence
      diabetic children's acquaintance with the correct method of insulin injection,
      psychological readiness to initiate insulin therapy, reduction in stress,
      anxiety, and fear of insulin injection.

PMID- 25763158
TI  - Evaluation of Glutathione S-transferase T1 (GSTT1) deletion polymorphism on type
      2 diabetes mellitus risk in a sample of Yazdian females in Yazd, Iran.
AB  - BACKGROUND: There has been much interest in the role of free radicals and
      oxidative stress in the pathogenesis of diabetes mellitus (DM). The aim of this
      study was to assess the possible association between genetic polymorphisms of the
      glutathione S-transferase-mu (GSTT1) and the risk of the development of DM in a
      sample of Yazdian females in Yazd, Iran. METHODS: This was a case-control study
      in which GSTT1 polymorphism was genotyped in 51 randomly selected DM patients and
      50 randomly selected healthy controls among Yazdian females whose ages ranged
      from 40 to 70. RESULTS: The frequencies of GSTT1 null genotype and GSTT1 present
      were 8 and 92%, respectively, in the control samples. In patients with type 2
      diabetes (T2DM), the frequencies of GSTT1 null genotype and GSTT1 present were 14
      and 86%, respectively. There were higher levels of triglycerides (TG), fasting
      blood sugar (FBS), total cholesterol (TC), low density lipoprotein (LDL), body
      mass index (BMI), and high density lipoprotein (HDL) in patients with GSTT1 null
      genotype than in patients with the GSTT1 present genotype. CONCLUSIONS: Our
      results indicated that the GSTT1 deletion polymorphism is a risk factor for T2DM.
      We did not determine any significant association between the GSTT1 null genotype
      and T2DM.

PMID- 25763159
TI  - Rhabdomyolysis due to Lamivudine administration in acute viral hepatitis B
      infection: a case report from Malaysia.
AB  - Rhabdomyolysis is a serious but rare side effect of Lamivudine treatment.
      Therefore, appropriate biochemical monitoring should be undertaken when it is
      used in the treatment of hepatitis B. This paper presents a case of Lamivudine
      associated rhabdomyolysis in a 31-year-old man with congenital heart disease and
      hepatitis B. Three days after starting Lamivudine, the patient developed myalgia.
      Significant muscle tenderness and swelling of the upper and lower limbs was
      discovered during a physical examination. Creatine kinase was markedly raised.
      Lamivudine-induced rhabdomyolysis was suspected and the drug was discontinued.
      Symptoms and creatine kinase activity improved within four days of Lamivudine
      cessation and hydration. Early identification of Lamivudine-induced
      rhabdomyolysis is key in preventing this potentially fatal drug reaction;
      withdrawal of Lamivudine may contribute to complete remission of rhabdomyolysis. 

PMID- 25763160
TI  - Cavitary pulmonary lesions in systemic lupus erythematosus: an unusual
      manifestation.
AB  - Systemic lupus erythematosus (SLE) is an autoimmune disease of unknown
      pathogenesis. The frequency of SLE with cavitary lesion manifestation is very
      rare and is thought to be due to infection or pulmonary embolism. A 19-year-old
      female diagnosed with SLE complicated by lupus nephritis and cavitary pulmonary
      lesion is presented in this case report. Other diseases that can lead to such
      lesions were ruled out in the patient. The patient improved briefly after the
      initiation of immunosuppressive therapy, but was unresponsive to supportive
      treatment due to pneumothorax. Pneumothorax is caused by cavitary lesions and
      possibly bronchopleural fistulas - these later caused respiratory distress and
      death. The patient did not show any improvement in the lesions after the
      initiation of immunosuppressive therapy. This case report suggests that the
      differential diagnosis of cavitary lung lesions should include SLE. 

PMID- 25763161
TI  - Comparison of urinary sodium and potassium in children older than two with
      idiopathic hypercalciuria and a healthy control group in Bandar-Abbas, Iran, in
      2013.
AB  - BACKGROUND: Idiopathic hypercalciuria is an important cause of symptoms related
      to the urinary system. The urinary excretion of high sodium and low potassium is
      a risk factor for hypercalciuria and urolithiasis. The aim of this study was to
      compare the urinary excretion of sodium and potassium by children older than two
      with idiopathic hypercalciuria and healthy control children in Bandar-Abbas,
      Iran. METHODS: This case control study was conducted during 2012 and 2013 in
      Bandar-Abbas, a city in southern Iran. The urinary excretion of sodium and
      potassium by 50 children with idiopathic hypercalciuria who were older than two
      was compared with that of 62 healthy children. IBM SPSS Statistics 21 software
      was used to analyze the data, and P < 0.05 was considered to be significant.
      RESULTS: Fifty children with idiopathic hypercalciuria (21 males and 29 females)
      were compared with 62 healthy children (19 males and 43 females). The results of
      the study indicated that there were no significant differences in the mean sodium
      and potassium levels in the urine of the two groups of children (P = 0.401 and P
      = 0.479, respectively.). CONCLUSION: The study showed no significant differences
      in the excretion of sodium and potassium in the urine of children with idiopathic
      hypercalciuria and that of healthy children in Bandar-Abbas. This finding was
      inconsistent with the results of similar studies conducted earlier. Therefore,
      more studies are needed on populations in different areas with various climates
      and difference races.

PMID- 25763162
TI  - A report of three cases of untreated Graves' disease associated with pancytopenia
      in Malaysia.
AB  - Generally, clinical presentations of Graves' disease range from asymptomatic
      disease to overt symptomatic hyperthyroidism with heat intolerance, tremor,
      palpitation, weight loss, and increased appetite. However, atypical presentation
      of Graves' disease with hematological system involvement, notably pancytopenia,
      is distinctly uncommon. Hereby, we present and discuss a series of three
      untreated cases of Graves' disease clinically presented with pancytopenia and the
      hematological abnormalities that responded well to anti-thyroid treatment. With
      resolution of the thyrotoxic state, the hematological parameters improved
      simultaneously. Thus, it is crucial that anti-thyroid treatment be considered in
      patients with Graves' disease and pancytopenia after a thorough hematological
      evaluation. 

PMID- 25763163
TI  - AIDS and hepatitis B and C high risk behaviors among 15 to 45 years old
      individuals in Bandar Abbas (Iran) in 2012.
AB  - BACKGROUND: AIDS and hepatitis are two of the most important health issues in the
      world. Adolescents and individuals in their reproductive years are important
      population for interventions in order to reduce high risk behaviors for
      transmission of sexually transmitted disease. However the prevalence of AIDS and
      hepatitis B and C is high in Bandar Abbas, no study is available about high risk
      behaviors related to these diseases in Bandar Abbas. The aim of the current study
      was to investigate high risk behaviors related to AIDS and hepatitis B and C
      among 15- to 45 year old individuals in Bandar Abbas, Southern Iran. METHOD: In
      this analytical study, 1938 participants between 15- and 45 years of age in
      Bandar Abbas in 2012 were selected to participate in this study. For each
      individual, the following information was sought: shared syringes, phlebotomy,
      tattoos, prisoning, drug abuse, amphetamine, alcohol, smoking, unsafe sexual
      contacts, as well as demographic information including age, sex, marital status,
      and education level. Data were analysed using SPSS version 16 (SPSS Inc. Chicago,
      Illinois, United States) using descriptive statistics and chi-square tests.
      RESULTS: A total of 8.4% reported having had tattoos; 10.3% reported previous
      phlebotomy. Individuals with prison history included 7.3% of our study population
      and their mean age was 31.4 years. Unsafe sexual contact was reported in 10.7% of
      the study sample. High risk behaviors were more common among individuals with a
      low educational level, and in alcohol users and amphetamine users (P<0.05).
      CONCLUSION: High risk behaviors are more common among individuals in their
      reproductive years. Increasing educational level and knowledge translation are
      effective in preventing AIDS and hepatitis high risk behaviors.

PMID- 25763164
TI  - Prevalence of night blindness in Bashagard district in Hormozgan, Iran, in 2011.
AB  - BACKGROUND: Night blindness is a visual disorder associated with unusual vision
      during the night or in darkness. Vitamin A deficiency (VAD), which is easily
      preventable, is the main known etiology of night blindness. Malnutrition is a
      common health issue in Bashagard and some other areas in the Hormozgan province
      of Iran. The aim of the current study was to determine the prevalence of night
      blindness in Bashagard. METHODS: This descriptive cross-sectional study was done
      on 814 Bashagard residences. Data was analyzed using SPSS software and
      descriptive studies. RESULTS: About 60% of the study participants were uneducated
      people or people with low education. Thirty-two out of 814 people that were
      studied had problems with night vision. Therefore, the prevalence of night
      blindness in Bashagard was 3.93%. CONCLUSION: Prevalence of night blindness in
      Bashagard is three times higher than its prevalence in all of Iran. Therefore,
      preventive interventions such as dietary regimes with vitamin A enrichments or
      supplementations are recommended.

PMID- 25763166
TI  - Amblyopia screening in children in Bandar Abbas (Iran) during 2011-2012.
AB  - BACKGROUND: Amblyopia is an acquired defect of vision caused by abnormal visual
      experience that occurs during childhood. Since early diagnosis is important in
      preventing further irreparable effects, the aim of this study was to investigate
      the outcome of amblyopia screening in children. METHODS: Data from the amblyopia
      screening program in the Welfare Department of Bandar Abbas during 2011-2012 were
      used. Suspected cases were referred to specialists in the Optometry clinic for
      screening purposes. Subsequently, patients who suffered from strabismus,
      amblyopia, or refractive errors were referred to ophthalmologists. SPSS version16
      was used to analyze the data. The significance level was set at P < 0.05.
      RESULTS: Of the 16,599 children examined in 2012, 2486 suspected cases of
      amblyopia were diagnosed and 168 being diagnosed with amblyopia after visit with
      ophthalmologist. The prevalence rate of amblyopia was 1.01%. In 2011, of 17,733
      cases, 2013 children were diagnosed as suspected cases and 171 patients were
      diagnosed to be amblyopic finally. CONCLUSIONS: The prevalence of amblyopia in
      this study was 0.96% and 1.01% in years 2011 and 2012 respectively, which was
      consistent with the results of studies in other countries. By considering the
      importance of diagnosing the prevalence of amblyopia on time in preschool and in
      order to prevent children's low vision or blindness in future, it is essential to
      increase the quality of the examinations that are conducted by the trainers.

PMID- 25763165
TI  - Lifestyle changes for prevention of breast cancer.
AB  - Breast cancer is the second most common cause of death from cancer among women.
      Lifestyle changes are shown to be important in the prevention of breast cancer.
      Diet, physical activity, smoking, alcohol use, and vitamin and mineral use are
      key factors influencing the risk of breast cancer among women. Because these
      factors are related to each other, it is difficult to assess their individual
      roles in breast cancer. Some of these factors are alterable, meaning that women
      can decrease their risk for breast cancer by changing their behavior. Breast
      cancer is associated with a high rate of mortality and morbidity among women.
      Therefore, it is logical to try to find ways to decrease the risk of developing
      breast cancer. Lifestyle changes seem to be an easy, effective, and economical
      way to help prevention breast cancer. In women with a confirmed breast cancer
      diagnosis who are under radiotherapy treatment after undergoing a mastectomy,
      lifestyle changes are still very important. Some factors, such as smoking
      cessation and prevention of weight gain, may improve the long-term survival
      chances of these patients. Therefore, ways to increase women's knowledge about
      the role of lifestyle changes in the prevention of breast cancer and in the
      survival of patients with diagnosed breast cancer should be considered and
      studied. 

PMID- 25763167
TI  - Evaluation of the relationship between prior uterine surgery and the incidence of
      adenomyosis in the Shariati Hospital in Bandar-Abbas, Iran, from 2001 to 2011.
AB  - BACKGROUND: Adenomyosis is a common benign disorder in pre-menopausal women that
      presents with uterine enlargement, pelvic pain, heavy menstrual bleeding, and
      dysmenorrhea. However, its risk factors have not been clearly determined. The aim
      of this study was to determine whether prior uterine surgery is a risk factor for
      adenomyosis. METHODS: In this cross-sectional study, we reviewed the medical
      records of all women who had hysterectomies for benign and a non-emergency,
      gynecological condition during 2001-2011 at Shariati Hospital in Bandar-Abbas,
      Iran. The variables in the study included age, gravidity, parity, abortion, prior
      uterine surgery, and the size of the uterus before hysterectomy. The data were
      analyzed by Microsoft Excel and SPSS version 16, by conducting descriptive
      statistics, by the t-test, and by Analysis of Variance (ANOVA). RESULTS: Of the
      191 participants, 72 women (37.7%) had pathologically-confirmed adenomyosis.
      Women with adenomyosis reported a history of prior uterine surgery more
      frequently than women without adenomyosis (P = 0.01), but age, menarche,
      gravidity, parity, and history of abortion were similar between the two groups (P
      > 0.05). CONCLUSION: History of prior uterine surgery is a risk factor for
      adenomyosis.

PMID- 25763168
TI  - In Vitro Activity of Tigecycline and Colistin against clinical isolates of
      Acinetobacter baumannii in Hospitals in Tehran and Bandar-Abbas, Iran.
AB  - BACKGROUND: The Acinetobacter species, particularly A. baumannii, has emerged as
      one of the main causes of nosocomial infections in recent years. The high
      prevalence of drug resistance in A. baumannii limits the therapeutic options for
      treating infections caused by these bacteria. The objective of this study was to
      determine the in vitro activity of Tigecycline and Colistin against clinical
      isolates of A. baumannii in Tehran and Bandar Abbas, Iran. METHODS: This study
      was conducted from March 2009 to November 2010 at three hospitals in Tehran and
      Bandar Abbas, Iran, using 165 Acinetobacter species isolated from clinical
      specimens. All isolates were subjected to PCR to detect bla OXA-51-like genes
      that are unique to Acinetobacter baumannii. Isolates that gave a band for the bla
      OXA-51-like genes were identified as A. baumannii. Anti-microbial susceptibility
      tests were performed for Tigecycline, Colistin, and other antibiotics. RESULTS:
      Sensitivity rates to Colistin and Polymyxin-B were 100%. Resistance rates for
      Tigecycline were 4.2% in Tehran and 8.8% in Bandar-Abbas according to Jones
      criteria, whereas, according to U.S. FDA criteria, the resistance rates were
      20.8% and 17.6%, respectively. CONCLUSIONS: New alternative drugs are needed for
      the treatment of drug resistant A. baumannii. Although Colistin appears to be a
      good choice, adverse reactions have limited its usage. Tigecycline is effective
      against A. baumannii isolates, and it shows promise for solving the problem.

PMID- 25763169
TI  - Hijacked journals are attacking the reliability and validity of medical research.

PMID- 25763170
TI  - Aging parents' caregiving and rehabilitating a brain-injured son: an
      autoethnography of a 10-year journey.
AB  - This autoethnography withdraws from information accumulated through a 10-year
      period of daily-weekly-monthly descriptive observation-recording (triangulated-
      parents & house-helper) of caregiving and rehabilitating of our brain injured son
      (survivor/care-receiver). We present it as an interactive voice of verbal
      conversation, thoughts, insights, and interpretations. It is delivered as a
      series of articulation intra-pulsated with our interrogation of societal-cultural
      religious perspectives, norms and biases, and aligns with the CAP (Creative
      Analytical Practices) method of Ellis. This autoethnography glows from the
      richness of information which encapsulates the challenges confronting us the
      aging parent caregivers, the gradual incremental mind mending achievement of our
      son, and the interactive verbalizations and thoughts, of the caregivers, care
      receiver, and other persons. The overwhelming mental and physical pain and
      struggle of the survivor and the aging caregivers and their sense of celebratory
      satisfaction with rehabilitation progress are highlighted. Interpretation and
      valuation of positive and negative responses of other persons provide a critical
      matrix to this autoethnography. We intend to inform other caregivers and relevant
      healthcare professionals through this autoethnography. 

PMID- 25763171
TI  - Correlation between elite male Iranian gymnast's wrist injuries and their
      anthropometric characteristics.
AB  - BACKGROUND: In gymnastics, wrists are under considerable force that causes
      various injuries. The influences of various risk factors have not been studied
      sufficiently to date to reduce the wrist injuries of gymnasts. The aim of this
      research was to determine the relationship between anthropometric characteristics
      and the wrist injuries of elite male gymnasts who took part in the Iranian
      Premier League and Division One in 2012. METHODS: This was a cross-sectional
      correlation study concerning the injuries of 43 elite male gymnasts. The extent
      of their wrist injuries was determined by a questionnaire and interviews. Also,
      their anthropometric characteristics were collected according to the criteria
      established by the International Society for the Advancement of Kinanthropometry.
      Event tree analysis and the Spearman rho correlation coefficient were used for
      statistical analysis. RESULTS: Among the gymnasts, 53.5% experienced wrist
      injuries over the past year, and the rate of wrist injuries was three per gymnast
      for one year. The incidents of skin and muscular injuries were the most prevalent
      type of injuries followed by Injuries to ligaments and bones respectively. Body
      weight was the only anthromopetric characteristic of the participants that was
      found to have a significant positive relationship with wrist injuries (P < 0.05).
      CONCLUSION: Gymnasts and their coaches should pay special attention to gymnasts'
      weight as an intrinsic risk factor and take the required actions to prevent wrist
      injuries.

PMID- 25763172
TI  - Effect of selenium on neurotoxicity in adult male mice exposed to formaldehyde.
AB  - BACKGROUND: Formaldehyde is used in medicine and industry, and it is known to
      have detrimental effects on various systems including the nervous system, by
      increasing oxidative stress. However, data are scarce related to substances that
      can protect against the neurotoxicity induced by formaldehyde. Therefore, this
      study was designed to assess the protective effects of selenium against the toxic
      effect of this compound. METHODS: A total of 48 adult male mice were divided
      randomly into six groups, i.e., (1) control, (2) treated with formaldehyde, (3)
      treated with formaldehyde plus 0.1 mg/kg selenium, (4) treated with formaldehyde
      plus 0.2 mg/kg selenium, (5) treated with formaldehyde plus 0.4 mg/kg selenium,
      and (6) treated with formaldehyde plus 0.8 mg/kg selenium. At the end of 14 days,
      the cerebellums were removed for histological evaluation. Morphological changes
      were examined using Image J software. The data were analyzed using SPSS software
      version 20.0 and analysis of variance (ANOVA). RESULTS: Formaldehyde caused a
      reduction in the numbers and sizes of Purkinje cells and granular cells; in
      addition, the thickness of the granular layer was thinner than that in the
      control mice (P < 0.05). Treatment with 0.1 mg/kg selenium resulted in an
      increase in the number of Purkinje cells as well as the area of the gray matter
      compared to those of the control mice. CONCLUSION: Formaldehyde-induced neuronal
      damage was prevented by the administration of 0.1 mg/kg selenium, hence this
      treatment shows therapeutic potential for the treatment of neurotoxicity.

PMID- 25763173
TI  - Fever after Cervical Ectopic Pregnancy; a case report from Gorgan, Iran.
AB  - Ectopic pregnancy is a rare condition, and, although its prevalence has decreased
      in recent years, it is still an important cause of mortality and morbidity in
      women. Cervical ectopic pregnancy is less than 1% of all ectopic pregnancies.
      Fever is one of signs of infection, and it is necessary to monitor patients
      closely for other signs of infection. This paper presents and discusses a case of
      cervical ectopic pregnancy with fever after treatment. The patient had a high
      fever that became worse after three hospitalizations. The probable cause of her
      pyelonephritis was a urinary catheter, although it had been removed earlier, and
      she was receiving antibiotic therapy. Even though cervical ectopic pregnancy is a
      rare condition, it has certain complications that must be managed appropriately. 

PMID- 25763174
TI  - Explanation-aware computing of the prognosis for breast cancer supported by IK
      DCBRC: Technical innovation.
AB  - BACKGROUND: Active research is being conducted to determine the prognosis for
      breast cancer. However, the uncertainty is a major obstacle in this domain of
      medical research. In that context, explanation-aware computing has the potential
      for providing meaningful interactions between complex medical applications and
      users, which would ensure a significant reduction of uncertainty and risks. This
      paper presents an explanation-aware agent, supported by Intensive Knowledge
      Distributed Case-Based Reasoning Classifier (IK-DCBRC), to reduce the uncertainty
      and risks associated with the diagnosis of breast cancer. METHODS: A meaningful
      explanation is generated by inferring from a rule-based system according to the
      level of abstraction and the reasoning traces. The computer-aided detection is
      conducted by IK-DCBRC, which is a multi-agent system that applies the case-based
      reasoning paradigm and a fuzzy similarity function for the automatic prognosis by
      the class of breast tumors, i.e. malignant or benign, from a pattern of
      cytological images. RESULTS: A meaningful interaction between the physician and
      the computer-aided diagnosis system, IK-DCBRC, is achieved via an intelligent
      agent. The physician can observe the trace of reasoning, terms, justifications,
      and the strategy to be used to decrease the risks and doubts associated with the
      automatic diagnosis. The capability of the system we have developed was proven by
      an example in which conflicts were clarified and transparency was ensured.
      CONCLUSION: The explanation agent ensures the transparency of the automatic
      diagnosis of breast cancer supported by IK-DCBRC, which decreases uncertainty and
      risks and detects some conflicts.

PMID- 25763175
TI  - Prevalence of obesity and overweight and their related factors among the adults
      of Mazandaran Province, Iran, in 2010.
AB  - BACKGROUND: Obesity is an unpleasant outcome of changes in the behavior and
      lifestyle, and it leads to premature inability and loss of job in most cases.
      This study aimed at determining the prevalence of obesity and overweight
      conditions and some related factors among the adults in Mazandaran Province,
      Iran. METHODS: This cross-sectional study was conducted in 2010. The data
      collection tool was a standard questionnaire provided by the World Health
      organization (WHO).The sample of this study was selected from all people in the
      age range of 15 to 64 who lived in the urban and rural areas of Mazandaran
      Province. The researchers studied 1000 people (500 males and 500 females). The
      data were analyzed using mean, standard deviation, chi-squared, linear
      regression, and Logistic regression in SPSS version 16 software. RESULTS: The
      average and the standard deviation of Body Mass Index (BMI) of the participants
      was 27.36+/-6.04 (25.76+/-4.5 for males and 28.95+/-6.9 for females), and the
      average prevalence of overweight was 34% (males: 35.8%, females: 32.2%); the
      average incidence of obesity was 28.4% (males: 17.8%, females: 39%).It was found
      that age groups of 35-44 (OR: 3.1, CI: 95%: 1.7-5.8), 45-54 (OR: 3.1, CI: 95%:
      1.7-5.8), and 55-64 (OR: 4.02, CI: 95%: 2.1-7.5) and being a housewife (OR: 2.3,
      95% CI: 1.03-5.1) were predictive of BMI values equal to or greater than 30.
      CONCLUSION: The results of this study showed that the prevalence of overweight
      and obesity was significant among people of Mazandaran Province. Therefore, it is
      recommended that educational-research centers and health authorities look for
      appropriate strategies to reduce the prevalence of this problem.

PMID- 25763176
TI  - Safety of nanotechnology in food industries.
AB  - The arrival of nanotechnology in various industries has been so rapid and
      widespread because of its wide-ranging applications in our daily lives. Nutrition
      and food service is one of the biggest industries to be affected by
      nanotechnology in all areas, changing even the nature of food itself. Whether
      it's farming, food packaging, or the prevention of microbial contamination the
      major food industries have seen dramatic changes because of nanotechnology.
      Different nanomaterials such as nanopowders, nanotubes, nano-fibers, quantum
      dots, and metal and metal-oxide nanoparticles are globally produced in large
      quantities due to their broad applicability in food-related industries. Because
      of the unique properties of nanostructures and nanomaterials - such as a large
      surface area, high activity, and small size, there is some concern about the
      potential for harmful adverse effects of used nanomaterials on health or the
      environment. However, because of tremendous advances in different industries,
      this concern may be unnecessary. This paper presents some uses of nanomaterials
      in food and related industries and their possible side-effects. This review
      covers the various aspects of nanomaterials and their impact on human exposure,
      safety, and environmental concerns. 

PMID- 25763177
TI  - Wake-Up. A Health Promotion Project for Sub-Saharan University Students: Results
      of Focus Group Sessions.
AB  - HIV/AIDS is seen as the major killer in developing countries however, non
      communicable diseases (NCDs), also referred to as chronic diseases, are the
      leading causes of death worldwide. University students are an important target
      for health promotion programmes because they are exposed to a new lifestyle where
      they have to determine on their own which diet to follow, whether or not to
      exercise, how much they drink alcohol or smoke, whether to have sex or abstain,
      as well as whether to practice safe sex or not Focus group sessions were held at
      a rural Sub-Saharan African University to assess students' knowledge on how to
      lead a healthy lifestyle. The results suggest a need for a health promotion
      intervention programme which should be culture-sensitive and considerate of the
      needs of university students.

PMID- 25763178
TI  - Similarity-based search of model organism, disease and drug effect phenotypes.
AB  - BACKGROUND: Semantic similarity measures over phenotype ontologies have been
      demonstrated to provide a powerful approach for the analysis of model organism
      phenotypes, the discovery of animal models of human disease, novel pathways, gene
      functions, druggable therapeutic targets, and determination of pathogenicity.
      RESULTS: We have developed PhenomeNET 2, a system that enables similarity-based
      searches over a large repository of phenotypes in real-time. It can be used to
      identify strains of model organisms that are phenotypically similar to human
      patients, diseases that are phenotypically similar to model organism phenotypes,
      or drug effect profiles that are similar to the phenotypes observed in a patient
      or model organism. PhenomeNET 2 is available at http://aber-owl.net/phenomenet.
      CONCLUSIONS: Phenotype-similarity searches can provide a powerful tool for the
      discovery and investigation of molecular mechanisms underlying an observed
      phenotypic manifestation. PhenomeNET 2 facilitates user-defined similarity
      searches and allows researchers to analyze their data within a large repository
      of human, mouse and rat phenotypes.

PMID- 25763179
TI  - Hypersensitivity to non-steroidal anti-inflammatory drugs (NSAIDs):
      classification of a Danish patient cohort according to EAACI/ENDA guidelines.
AB  - BACKGROUND: Non-steroidal anti-inflammatory drugs (NSAIDs) are reported to be the
      second most common cause of drug hypersensitivity. In 2011, experts from the
      EAACI/ENDA group and GA(2)LEN proposed a new classification system for NSAID
      hypersensitivity. The aim of this study was to classify a patient cohort with a
      history of NSAID hypersensitivity according to this system. METHODS: Patients
      with a clinical history of NSAID hypersensitivity referred to the Allergy Centre,
      Odense University Hospital between 2002 and 2011 and evaluated with oral
      provocation tests (OPTs) were included in the study. Medical records were
      retrospectively investigated with respect to the culprit NSAID(s), underlying
      diseases and symptoms at the primary reaction and during oral provocation tests
      (OPTs). Data was supplemented with a questionnaire. Classification according to
      EAACI guideline was based on these findings. RESULTS: In total 149 patients were
      included. Of those, 39 patients (26.2%) had a positive OPT. Twenty-nine patients
      were classified as cross-reactive responders and 9 patients as single NSAID
      responders after positive OPTs with the culprit NSAID, but not to acetylsalicylic
      acid. All single NSAID responders reacted to non-pyrazolone drugs. Only one
      patient could not be classified according to the EAACI/ENDA system. An overlap
      between respiratory and cutaneous symptoms was found in 15/39 (38%) of patients.
      CONCLUSIONS: All but one of our patients could be classified according to the
      EAACI classification system. Overlaps between different classes may occur much
      more commonly than expected.

PMID- 25763180
TI  - Hydrocortisone enhances the barrier properties of HBMEC/cibeta, a brain
      microvascular endothelial cell line, through mesenchymal-to-endothelial
      transition-like effects.
AB  - BACKGROUND: Because in vitro blood-brain barrier (BBB) models are important tools
      for studying brain diseases and drug development, we recently established a new
      line of conditionally immortalized human brain microvascular endothelial cells
      (HBMEC/cibeta) for use in such models. Since one of the most important functional
      features of the BBB is its strong intercellular adhesion, in this study, we aimed
      at improving HBMEC/cibeta barrier properties by means of culture media
      modifications, thus enhancing their use for future BBB studies. In addition, we
      simultaneously attempted to obtain insights on related mechanistic properties.
      METHODS: Several types of culture media were prepared in an effort to identify
      the medium most suitable for culturing HBMEC/cibeta. The barrier properties of
      HBMEC/cibeta were examined by determining Na(+)-fluorescein permeability and
      transendothelial electric resistance (TEER). Endothelial marker mRNA expression
      levels were determined by quantitative real-time polymerase chain reaction.
      Adherens junction (AJ) formation was examined by immunocytochemistry. Cell
      migration ability was analyzed by scratch assay. Furthermore, cellular lipid
      composition was examined by liquid chromatography-time-of-flight mass
      spectrometry. RESULTS: Our initial screening tests showed that addition of
      hydrocortisone (HC) to the basal medium significantly reduced the Na(+)
      fluorescein permeability and increased the TEER of HBMEC/cibeta monolayers. It
      was also found that, while AJ proteins were diffused in the cytoplasm of
      HBMEC/cibeta cultured without HC, those expressed in cells cultured with HC were
      primarily localized at the cell border. Furthermore, this facilitation of AJ
      formation by HC was in concert with increased endothelial marker mRNA levels and
      increased ether-type phosphatidylethanolamine levels, while cell migration was
      retarded in the presence of HC. CONCLUSIONS: Our results show that HC
      supplementation to the basal medium significantly enhances the barrier properties
      of HBMEC/cibeta. This was associated with a marked phenotypic alteration in
      HBMEC/cibeta through orchestration of various signaling pathways. Taken together,
      it appears that overall effects of HC on HBMEC/cibeta could be summarized as
      facilitating endothelial differentiation characteristics while concurrently
      retarding mesenchymal characteristics.

PMID- 25763181
TI  - Topical allogeneic platelet-rich plasma treatment for a massive cutaneous lesion
      induced by disseminated intravascular coagulation in a toy breed dog.
AB  - A 2-year-old intact female miniature Pinscher weighing 1.7 kg with a body
      condition score of 2/5 was presented for acute vomiting, lethargy for 2 days, and
      large petechial skin lesions on the hip region including the tail. Acute
      pancreatitis was diagnosed by clinical signs, strong positive cPLI test,
      laboratory test and ultrasound appearance. While the clinical signs associated
      with acute pancreatitis had improved in 3-5 days, lesion of petechial appeared on
      the left hip region 7 days after the presentation, with a fast progression into a
      necrotic tissue along the left side hip. Allogenic platelet rich plasma (PRP)
      with Weibrich and Kleis method was administered to promote skin healing and
      regeneration. Gradual and complete improvement in the dog's wound lesions was
      noted approximately 1 month after applying allogeneic topical PRP. In this case
      report, allogeneic PRP was applied to a large regional cutaneous defect caused by
      coagulopathy induced by acute pancreatitis. Topical application of PRP in this
      case was unique in that allogeneic PRP was used instead of autologous PRP for the
      first time in cutaneous soft-tissue wound management in the veterinary medical
      field. 

PMID- 25352979
TI  - The Human Release Hypothesis for biological invasions: human activity as a
      determinant of the abundance of invasive plant species.
AB  - Research on biological invasions has increased rapidly over the past 30 years,
      generating numerous explanations of how species become invasive. While the
      mechanisms of invasive species establishment are well studied, the mechanisms
      driving abundance patterns (i.e. patterns of population density and population
      size) remain poorly understood. It is assumed that invasive species typically
      have higher abundances in their new environments than in their native ranges, and
      patterns of invasive species abundance differ between invaded regions. To explain
      differences in invasive species abundance, we propose the Human Release
      Hypothesis. In parallel to the established Enemy Release Hypothesis, this
      hypothesis states that the differences in abundance of invasive species are found
      between regions because population expansion is reduced in some regions through
      continuous land management and associated cutting of the invasive species. The
      Human Release Hypothesis does not negate other important drivers of species
      invasions, but rather should be considered as a potentially important
      complementary mechanism. We illustrate the hypothesis via a case study on an
      invasive rose species, and hypothesize which locations globally may be most
      likely to support high abundances of invasive species. We propose that more
      extensive empirical work on the Human Release Hypothesis could be useful to test
      its general applicability. 

PMID- 25763183
TI  - Cross-border comparison of the Dutch and German guidelines on multidrug-resistant
      Gram-negative microorganisms.
AB  - BACKGROUND: In all European countries, hospital-acquired infections caused by
      Gram-negative multidrug-resistant microorganisms (GN-MDRO) are a major health
      threat, as these pathogens cannot be adequately treated anymore, or the start of
      effective antibiotic treatment is delayed. The efforts to limit the selection and
      spread of GN-MDRO remains a problem in cross-border healthcare, as the national
      guidelines on hygiene standards applicable for patients colonized or infected
      with GN-MDRO in hospitals are not harmonized between European countries. METHODS:
      In order to point out the similarities and differences in the national guidelines
      of Germany and The Netherlands regarding GN-MDRO, guidelines were compared and an
      expert workshop was organized by the INTERREG IVa project EurSafety Health-net.
      RESULTS: Both guidelines divide the Gram-negative organisms into subgroups based
      on bacterial species and antibiotic susceptibility patterns in order to define
      multidrug-resistant variants of these bacteria. However, the Dutch guideline
      defines that GN-MDRO Enterobacteriaceae requires testing for certain mechanisms
      causing antibiotic resistance, whereas the German guideline makes use of a newly
      created classification scheme, based on phenotypic characterization. Besides
      diagnostic issues, the main difference between the Dutch and German guideline is
      the divergent evaluation of ESBL-producing Enterobacteriaceae. Special hygiene
      measures are required for all patients with ESBL-producing Enterobacteriaceae in
      The Netherlands, whereas the German guideline recommends special precautions only
      for those cases in which patients are colonized or infected with strains showing
      co-resistance to ciprofloxacin ("3MRGN"). CONCLUSIONS: The usage of consistent
      terminology and harmonized diagnostic procedures would improve the possibilities
      for infection prevention, treatment and patient safety. Prevention of severe non
      treatable infections and outbreaks due to MDRO, caused by an increased population
      seeking medical treatment abroad together with an increased number of highly
      susceptible individuals demands gathering of regional data, and data comparable
      between the two sides of the Dutch-German border. The necessity to cooperate
      multidisciplinary and across borders is required to prevent a post-antibiotic era
      - in which common infections and minor injuries may lead to death.

PMID- 25763184
TI  - 16S gut community of the Cameron County Hispanic Cohort.
AB  - BACKGROUND: Obesity and type 2 diabetes (T2D) are major public health concerns
      worldwide, and their prevalence has only increased in recent years. Mexican
      Americans are disproportionately afflicted by obesity and T2D, and rates are even
      higher in the United States-Mexico border region. To determine the factors
      associated with the increased risk of T2D, obesity, and other diseases in this
      population, the Cameron County Hispanic Cohort was established in 2004. RESULTS:
      In this study, we characterized the 16S gut community of a subset of 63 subjects
      from this unique cohort. We found that these communities, when compared to Human
      Microbiome Project subjects, exhibit community shifts often observed in obese and
      T2D individuals in published studies. We also examined microbial network
      relationships between operational taxonomic units (OTUs) in the Cameron County
      Hispanic Cohort (CCHC) and three additional datasets. We identified a group of
      seven genera that form a tightly interconnected network present in all four
      tested datasets, dominated by butyrate producers, which are often increased in
      obese individuals while being depleted in T2D patients. CONCLUSIONS: Through a
      combination of increased disease prevalence and relatively high gut microbial
      homogeneity in the subset of CCHC members we examined, we believe that the CCHC
      may represent an ideal community to dissect mechanisms underlying the role of the
      gut microbiome in human health and disease. The lack of CCHC subject gut
      community segregation based on all tested metadata suggests that the community
      structure we observe in the CCHC likely occurs early in life, and endures. This
      persistent 'disease'-related gut microbial community in CCHC subjects may enhance
      existing genetic or lifestyle predispositions to the prevalent diseases of the
      CCHC, leading to increased attack rates of obesity, T2D, non-alcoholic fatty
      liver disease, and others.

PMID- 25763185
TI  - Volume reduction of benign thyroid nodules 3 months after a single treatment with
      high-intensity focused ultrasound (HIFU).
AB  - BACKGROUND: High-intensity focused ultrasound (HIFU) is a promising, non-invasive
      technique in treating benign thyroid nodules (TNs). The aim of this study was to
      evaluate the efficacy of HIFU to induce clinically meaningful shrinkage in benign
      predominantly solid TNs and to identify variables that influence or predict the
      magnitude of TN volume reduction. METHODS: For each of ten subjects, HIFU
      treatment was conducted on a single nodule. Nodular volume was measured
      sonographically at baseline and at 3 months post-procedure. Nodular function and
      early treatment assessment was done scintigraphically. RESULTS: Median nodular
      volume reduction was 0.7 ml absolute and 48.8% relative to pre-interventional
      size (p < 0.05). Absolute shrinkage was negatively correlated with the average
      treatment depth (tau = -0.61, p < 0.05). Absolute nodular volume was positively
      correlated with the scintigraphic nodular uptake reduction (tau = 0.66, p <
      0.05). CONCLUSIONS: HIFU treatment of benign predominantly solid TNs appears to
      be safe and effective for inducing nodular shrinkage. Despite potential for
      improvement, a single treatment session with HIFU is already a viable alternative
      to more standard methods. The feasibility of multiple HIFU treatments requires
      further investigation. Due to the small sample size, the findings of this
      analysis need conformation by larger studies.

PMID- 25763187
TI  - In-situ Pb(2+) remediation using nano iron particles.
AB  - Originally, application of nano zero valent iron (nZVI) particles for the removal
      of lead (Pb(2+)) in porous media was studied. At first, stabilized nZVI (S-nZVI)
      was prepared and characterized, then used in batch and continuous systems. Based
      on the batch experiments, corresponding reaction kinetics well fitted with the
      pseudo-first-order adsorption model, and reaction rate ranged from 0.01 to 0.04
      g/mg/min depend on solution pH and the molar ratio between Fe and Pb. In batch
      tests, optimal condition with more than 90% removal efficiency at 60 min was
      observed at a pH range of 4 to 6 and Fe/Pb ratio more than 2.5. Continuous
      experiments exposed that Pb(2+) remediation was as well influenced by seepage
      velocity, grain size, and type of porous media. The maximum Pb(2+) removal
      efficiency in batch and bench-scale systems were 97% and 81%, correspondingly.
      The results have shown the ability of S-nZVI to use in permeable reactive
      barriers, as an efficient adsorbent for Pb(2+), because of its excellent
      stability, high reducing power, and a large surface area. 

PMID- 25763186
TI  - Predictive factors of successful microdissection testicular sperm extraction.
AB  - Azoospermia in men requires microsurgical reconstruction or a procedure for sperm
      retrieval with assisted reproduction to allow fertility. While the chance of
      successful retrieval of sperm in men with obstructive azoospermia approaches
      >90%, the chances of sperm retrieval in men with non-obstructive azoospermia
      (NOA) are not as high. Conventional procedures such as fine needle aspiration of
      the testis, testicular biopsy and testicular sperm extraction are successful in
      20-45% of men with NOA. With microdissection testicular sperm extraction (micro
      TESE), the chance of successful retrieval can be up to 60%. Despite this
      increased success, the ability to counsel patients preoperatively on their
      probability of successful sperm retrieval has remained challenging. A combination
      of variables such as age, serum FSH and inhibin B levels, testicular size,
      genetic analysis, history of Klinefelter syndrome, history of cryptorchidism or
      varicocele and histopathology on diagnostic biopsy have provided some insight
      into the chance of successful sperm retrieval in men with NOA. The goal of this
      review was to evaluate the preoperative factors that are currently available to
      predict the outcome for success with micro-TESE. 

PMID- 25763189
TI  - The association between long working hours and the metabolic syndrome: evidences
      from the 5th Korean National Health and Nutrition Examination Survey of 2010 and
      2012.
AB  - OBJECTIVES: This study was conducted in order to evaluate the association between
      the working hours of Korean employees and the metabolic syndrome and the effects
      of long working hours on metabolic syndrome based on the 5th Korean National
      Health and Nutrition Examination Survey (2010-2012). METHODS: Based on the 5th
      Korean National Health and Nutrition Examination Survey (2010-2012), 4,456 Korean
      employees without shift work, aged over 15, who work 30 hours or more per week
      were targeted in this study. The association between the general characteristics,
      including age, smoking, alcohol drinking, exercise, and the metabolic syndrome
      criteria defined by International Diabetes Federation (IDF) and weekly working
      hours were analyzed. In addition, the association between weekly working hours
      and the metabolic syndrome of the subjects stratified by gender was analyzed
      through multiple logistic regression analyses and generalized linear mixed model
      after adjusting the general characteristics. RESULTS: In the results of
      stratified analysis by gender, in male subjects, in comparison with the 30-39
      weekly working hours group, there were no significant adjusted odds ratios to the
      other working hours groups. In female subjects, in comparison with the 30-39
      weekly working hours group, there were no significant adjusted odds ratios to the
      other working hours groups. In addition, no trend associations were observed
      among weekly working hour groups in both stratified genders. CONCLUSION: No
      significant differences in prevalence of metabolic syndrome of the subjects
      stratified by gender were found according to weekly increasing working hours.
      However, due to some limitations of this study, further prospective studies may
      be necessary for verification.

PMID- 25763190
TI  - Effects of calci soya balance and vitagnus on menopausal symptoms.
AB  - BACKGROUND: Menopause is a period of women's lives with changes and symptoms that
      affect their work, sleep and quality of life. Therefore, it is important to
      overcome these symptoms. OBJECTIVES: The aim of the present study was to compare
      the effects of Calci soya balance and Vitagnus on menopausal symptoms. PATIENTS
      AND METHODS: This double-blinded controlled trial study was performed in public
      health centers of Tehran University of Medical Sciences (2011-2012). Seventy
      postmenopausal women with menopausal symptoms were randomly divided into two
      groups of treatments with Vitagnus and Calci soya balance. Data were collected
      using interviews, answering Cooperman's index questionnaires before four and
      eight weeks after the treatment. Descriptive and analytic statistics were used
      for analyzing the data. RESULTS: In both groups, Wilcoxon test showed a
      significant decrease in the mean of Cooperman's menopausal index as well as after
      four and eight weeks of treatment (P = 0.000). Mann-Whitney test did not show any
      significant differences between the two groups, before and after four and eight
      weeks of treatment. CONCLUSIONS: The results showed that both Vitagnus and Calci
      soya balance were effective on reduction of menopausal symptoms to a similar
      extent and medical community can administer each of these two drugs based on
      patients' conditions and costs.

PMID- 25763191
TI  - Establishing a framework of influential factors on empowering primary school
      students in peer mediation.
AB  - BACKGROUND: Empowerment of children and adolescents in terms of social skills is
      critical for promoting their social health. OBJECTIVES: This study attempts to
      explore a framework of influential factors on empowering primary school students
      by means of peer mediation from the stakeholders' point of view, as a qualitative
      content analysis design. PATIENTS AND METHODS: This study was a qualitative
      content analysis (conventional method). Seven focused group discussions and six
      in-depth interviews were conducted with schoolchildren, parents and education
      authorities. Following each interview, recordings were entered to an open code
      software and analyzed. Data collection was continued up to data saturation.
      RESULTS: Within the provided framework, the participants' views and comments were
      classified into two major categories "educational empowerment" and "social
      empowerment", and into two themes; "program" and "advocacy". The "program" theme
      included factors such as design and implementation, development, maintenance and
      improvement, and individual and social impact. The "advocacy" theme included
      factors such as social, emotional and physical support. CONCLUSIONS: The
      explained framework components regarding peer mediation are useful to design
      peace education programs and to empower school-age children in peer mediation.

PMID- 25763192
TI  - Superior mesenteric artery syndrome accompanying with nutcracker syndrome: a case
      report.
AB  - INTRODUCTION: Superior mesenteric artery syndrome is an uncommon cause of
      duodenal obstruction, and its manifestations are generally associated with
      compression on the third part of the duodenum between the abdominal aorta and
      superior mesenteric artery. CASE PRESENTATION: In this report, a patient is
      described presenting with epigastric pain and weight loss due to superior
      mesenteric artery syndrome. The patient has also nutcracker syndrome, which is
      the compression of the left renal vein between the aorta and the superior
      mesenteric artery at its origin. CONCLUSIONS: In addition to an appropriate
      clinical history, CT findings indicating decreased aortomesenteric angle and a
      shortened aortomesenteric distance can suggest the diagnosis for both the
      superior mesenteric artery syndrome and accompanying nutcracker syndrome.

PMID- 25763193
TI  - Risk factors and prevalence of vitamin d deficiency among Iranian women attending
      two university hospitals.
AB  - BACKGROUND: Several studies indicated that there is a high prevalence of vitamin
      D deficiency in Middle East countries. OBJECTIVES: The aim of this study was to
      determine the prevalence and assess some risk factors of vitamin D deficiency
      among women attending our clinics in Tehran, the capital of Iran. PATIENTS AND
      METHODS: Five hundred and thirty-eight women aged 20-80 years were entered in
      this cross-sectional study from 2011 to 2012. Serum 25-hydroxy vitamin D levels
      were measured in all participants after recruiting their demographic and
      anthropometric data and past medical histories. Deficiency was defined as levels
      less than 35 nmol/L and classified as mild (>= 25 nmol/L), moderate (12.5-25
      nmol/L) and severe (<= 12.5 nmol/L). RESULTS: The prevalence of vitamin D
      deficiency was 69%; mild, moderate and severe degrees were seen in %10.4, %38.3,
      and %20.3 respectively. Analysis of logistic regression shows that age (OR:0.96,
      CI: 0.93-0.97), menopause (OR: 0.44, CI: 0.21-0.99) and consumption of
      multivitamin supplements (OR: 2.67, CI: 1.4-5) were independent predictive
      factors for Vitamin D deficiency. CONCLUSIONS: This study showed a high
      prevalence of vitamin D deficiency among Iranian women especially in reproductive
      ages.

PMID- 25763194
TI  - Financial Management Reforms in the Health Sector: A Comparative Study Between
      Cash-based and Accrual-based Accounting Systems.
AB  - BACKGROUND: Financial management and accounting reform in the public sectors was
      started in 2000. Moving from cash-based to accrual-based is considered as the key
      component of these reforms and adjustments in the public sector. Performing this
      reform in the health system is a part of a bigger reform under the new public
      management. OBJECTIVES: The current study aimed to analyze the movement from cash
      based to accrual-based accounting in the health sector in Iran. PATIENTS AND
      METHODS: This comparative study was conducted in 2013 to compare financial
      management and movement from cash-based to accrual-based accounting in health
      sector in the countries such as the United States, Britain, Canada, Australia,
      New Zealand, and Iran. Library resources and reputable databases such as Medline,
      Elsevier, Index Copernicus, DOAJ, EBSCO-CINAHL and SID, and Iranmedex were
      searched. Fish cards were used to collect the data. Data were compared and
      analyzed using comparative tables. RESULTS: Developed countries have implemented
      accrual-based accounting and utilized the valid, reliable and practical
      information in accrual-based reporting in different areas such as price and
      tariffs setting, operational budgeting, public accounting, performance evaluation
      and comparison and evidence based decision making. In Iran, however, only a few
      public organizations such as the municipalities and the universities of medical
      sciences use accrual-based accounting, but despite what is required by law, the
      other public organizations do not use accrual-based accounting. CONCLUSIONS:
      There are advantages in applying accrual-based accounting in the public sector
      which certainly depends on how this system is implemented in the sector.

PMID- 25763195
TI  - A model for decision making for intensive care unit admission in source limited
      hospitals.
AB  - BACKGROUND: Demand for ICU beds is exceeding its supply. Since the sources are
      limited in some centers, it is necessary to design a model to identify the
      patients who benefit more from ICU beds. OBJECTIVES: The present study aimed to
      develop a model to prioritize adult patients according to their clinical
      indications by a three rounded Delphi method study. PATIENTS AND METHODS: In this
      study, 22 physicians who practiced in a source limited hospital in southern Iran
      were invited to participate in a three phase Delphi survey. RESULTS: At first,
      the panelists recommended 30 indications. The indications in the first checklist
      plus those obtained by literature review formed the second checklist which
      contained 36 items. The items were scored from 0 to 10 by the panelists.
      According to the scores, the indications were categorized into three priority
      levels, which were confirmed by the panelists in the third round. CONCLUSIONS:
      This simple checklist contains the indications for ICU admission categorized into
      three priority levels. This checklist can be considered as a guide for physicians
      who practice in hospitals with limited number of ICU beds.

PMID- 25763196
TI  - The Impact of Different Permissible Exposure Limits on Hearing Threshold Levels
      Beyond 25 dBA.
AB  - BACKGROUND: Development of noise-induced hearing loss is reliant on a few factors
      such as frequency, intensity, and duration of noise exposure. The occurrence of
      this occupational malady has doubled from 120 million to 250 million in a decade.
      Countries such as Malaysia, India, and the US have adopted 90 dBA as the
      permissible exposure limit. According to the US Occupational Safety and Health
      Administration (OSHA), the exposure limit for noise is 90 dBA, while that of the
      US National Institute of Occupational Safety and Health (NIOSH) is 85 dBA for 8
      hours of noise exposure. OBJECTIVES: This study aimed to assess the development
      of hearing threshold levels beyond 25 dBA on adoption of 85 dBA as the
      permissible exposure limit compared to 90 dBA. PATIENTS AND METHODS: This is an
      intervention study done on two automobile factories. There were 203 employees
      exposed to noise levels beyond the action level. Hearing protection devices were
      distributed to reduce noise levels to a level between the permissible exposure
      limit and action level. The permissible exposure limits were 90 and 85 dBA in
      factories 1 and 2, respectively, while the action levels were 85 and 80 dBA,
      respectively. The hearing threshold levels of participants were measured at
      baseline and at first month of postshift exposure of noise. The outcome was
      measured by a manual audiometer. McNemar and chi-square tests were used in the
      statistical analysis. RESULTS: We found that hearing threshold levels of more
      than 25 dBA has changed significantly from pre-intervention to post-intervention
      among participants from both factories (3000 Hz for the right ear and 2000 Hz for
      the left ear). There was a statistically significant association between
      participants at 3000 Hz on the right ear at 'deteriorated' level ( chi2 (1) =
      4.08, phi = - 0.142, P = 0.043), whereas there was worsening of hearing threshold
      beyond 25 dBA among those embraced 90 dBA. CONCLUSIONS: The adoption of 85 dBA as
      the permissible exposure limit has preserved hearing threshold level among
      participants at 3000 Hz compared to those who embraced 90 dBA.

PMID- 25763197
TI  - Investigating Antithyroid Effects of Propylthiouracil on the Ischemia and
      Reperfusion Injury in Rat' Kidney and Determining the Role of Nitric Oxide in
      Mediating this Effect.
AB  - BACKGROUND: Renal ischemia/reperfusion injury (IRI) is a major problem in renal
      transplantation, which occurs during the process of organ retrieval and storage,
      and is closely associated with acute rejection episodes and late allograft
      failure. Recent studies have revealed a new phenomenon called "chemical
      preconditioning" that can induce tolerance against the ischemic stress via a
      variety of proposed pathways especially nitric oxide (NO) system.
      Propylthiouracil (PTU) is suggested to modulate the intracellular NO signaling.
      OBJECTIVES: In this study, we investigated the preconditioning properties of
      chronic pretreatment with PTU in preventing renal IRI. In addition, we evaluated
      the involvement of NO pathway. MATERIALS AND METHODS: Sixty adult male Wistar
      rats were allocated into six groups. All groups underwent right nephrectomy 15
      days before intervention. In groups 1 (Chronic PTU + L-NG-nitro arginine methyl
      ester [L-NAME]) and 2 (Chronic PTU) oral PTU (500 mg/L in water) treatment was
      started 15 days before right nephrectomy to achieve the therapeutic plasma level
      of PTU. Fourteen days after nephrectomy, animals received either L-NAME (10
      mg/kg) or its vehicle and renal IRI was induced 45 minutes later. Groups 3 and 4
      (Control) received respectively L-NAME (10 mg/kg) and its vehicle 45 minutes
      before IRI. The last two groups were normal sham operated rats and PTU + sham.
      Rats were killed 24 hours after IRI. The blood samples were collected and
      assessed for serum blood urea nitrogen (BUN) and creatinine (Cr) level, and
      tissue samples were fixed in formalin for histopathologic scoring of tubular
      damage (H-score). RESULTS: The mean BUN, Cr, and H-score of control group were
      176.66 +/- 12.24 mmol/L, 4.45 +/- 0.44 MUmol/L, and 83.5% +/- 3.5%, respectively.
      Chronic pretreatment with PTU significantly improved BUN (40.4 +/- 6.1 mmol/L),
      Cr (0.96 +/- 0.068 MUmol/L), and H-score (7.83% +/- 4.02%) in IRI animals in
      comparison to those that were not treated with chronic PTU (P < 0.001) and L
      NAME; however, it did not completely reversed the chronic PTU-induced protection
      (BUN, 93.33 +/- 12.22 mmol/L; Cr, 2.7 +/- 1.15 MUmol/L, and H-score, 24.83% +/-
      3.5%). There was no significant difference between rats that were treated with L
      NAME alone (group 5) and the control group. CONCLUSIONS: Our study demonstrates
      that preconditioning of kidney with chronic PTU administration protects renal
      tissue against IRI and this phenomenon was mediated through NO system. The
      results suggest a potential indication for using PTU to protect the kidney before
      transplantations and to reduce the risk of tissue rejection afterwards.

PMID- 25763198
TI  - The etiologies of low back pain in patients with lumbar disk herniation.
AB  - BACKGROUND: Low back pain (LBP) is a common complaint in population that lowers
      the quality of life. The main etiology of LBP is recognized in about 20% of
      patients while it is attributed to lumbar disk herniation (LDH) in 80% of cases
      and causes some unnecessary lumbar surgeries without realizing the definite
      cause. OBJECTIVES: This study was planned to evaluate the etiologies of LBP in
      patients who had LDH to clarify whether the disc herniation is the main cause of
      patients' pain or other diseases were responsible for this kind of pain.
      MATERIALS AND METHODS: In this cross-sectional study, we analyzed the medical
      profiles of the patients with proven LDH in a private clinic in Mashhad City,
      Iran, between 2005 and 2012, for demographic and the etiologies of LBP with
      clinical and paraclinical studies. We also calculated the incidence of each
      etiology by SPSS 13. RESULTS: In our study, among 1250 patients with proven LDH
      by MRI, 500 patients (40%) had chronic LBP and the most common causes of LBP were
      heavy constant working (40.2%), osteoporosis (35.6%), and sacroiliac joint pain
      (34.6%), consecutively. Interestingly, LDH had the ninth rank among the common
      cause of LBP. CONCLUSIONS: In this study, we found that in spite of previous
      beliefs, discopathies were not common etiologies of LBP. Thus, even in patients
      with proven LDH by imaging studies, the physician should perform a thorough
      evaluation for other causes of LBP to avoid unnecessary lumbar surgeries.

PMID- 25763199
TI  - Virulence Gene Profiles of Multidrug-Resistant Pseudomonas aeruginosa Isolated
      From Iranian Hospital Infections.
AB  - BACKGROUND: The most common hospital-acquired pathogen is Pseudomonas aeruginosa.
      It is a multidrug resistant bacterium causing systemic infections. OBJECTIVES:
      The present study was carried out in order to investigate the distribution of
      virulence factors and antibiotic resistance properties of Pseudomonas aeruginosa
      isolated from various types of hospital infections in Iran. PATIENTS AND METHODS:
      Two-hundred and seventeen human infection specimens were collected from
      Baqiyatallah and Payambaran hospitals in Tehran, Iran. The clinical samples were
      cultured immediately and samples positive for P. aeruginosa were analyzed for the
      presence of antibiotic resistance and bacterial virulence genes using PCR
      (polymerase chain reaction). Antimicrobial susceptibility testing was performed
      using disk diffusion methodology with Mueller-Hinton agar. RESULTS: Fifty-eight
      out of 127 (45.66%) male infection specimens and 44 out of 90 (48.88%) female
      infection specimens harbored P. aeruginosa. Also, 65% (in male specimens) and 21%
      (in female specimens) of respiratory system infections were positive for P.
      aeruginosa, which was a high rate. The genes encoding exoenzyme S (67.64%) and
      phospholipases C (45.09%) were the most common virulence genes found among the
      strains. The incidences of various beta-lactams encoding genes, including bla
      TEM, bla SHV, bla OXA, bla CTX-M, bla DHA, and bla VEB were 94.11%, 16.66%,
      15.68%, 18.62%, 21.56%, and 17.64%, respectively. The most commonly detected
      fluoroquinolones encoding gene was gyrA (15. 68%). High resistance levels to
      penicillin (100%), tetracycline (90.19%), streptomycin (64.70%), and erythromycin
      (43.13%) were observed too. CONCLUSIONS: Our findings should raise awareness
      about antibiotic resistance in hospitalized patients in Iran. Clinicians should
      exercise caution in prescribing antibiotics, especially in cases of human
      infections.

PMID- 25763200
TI  - Corticosteroid in the treatment of moderate to severe thrombocytopenia due to
      leptospirosis.
AB  - BACKGROUND: Thrombocytopenia is associated with a bad prognosis in Leptospirosis.
      OBJECTIVES: We investigated the effect of corticosteroids to improve
      thrombocytopenia due to leptospirosis. PATIENTS AND METHODS: In a clinical trial,
      all patients admitted with leptospirosis in Razi Hospital of Ghaemshahr, north of
      Iran were enrolled in a 2-year study. Totally, 56 patients with moderate to
      severe thrombocytopenia were randomized to control and treatment groups. The
      treatment group received corticosteroid (prednisolone 1 mg/kg/day for maximum one
      week) in addition to the standard antibiotic therapy. RESULTS: There was no
      significant difference regarding age and gender between the two groups (P =
      0.254, P = 0.789, respectively). The mean duration to improve thrombocytopenia
      was 4.41 +/- 0.197 days in the treatment group and 5.72 +/- 0.318 days in the
      control group, which was significantly different (P = 0.003). Duration of
      hospitalization in the treatment group was 5.24 +/- 0.244 days and 6.23 +/- 0.329
      days in the control group, which was significantly different (P = 0.028). The two
      groups had no significant difference regarding mortality, intubation, level of
      platelet, duration of ICU admission and pulmonary, renal or hepatic involvement.
      CONCLUSIONS: Corticosteroid therapy decreased the length of hospitalization only
      in severe subgroup thrombocytopenia, but not in the moderate subgroup.

PMID- 25763201
TI  - Effects of coenzyme q10 supplementation on serum lipoproteins, plasma fibrinogen,
      and blood pressure in patients with hyperlipidemia and myocardial infarction.
AB  - BACKGROUND: Low plasma concentrations of coenzyme Q10 (CoQ10) have been
      associated with concentration of lipoproteins and other factors contributing to
      coronary heart diseases. OBJECTIVES: The present investigation aimed to improve
      the blood pressure and serum lipoproteins concentration in patients with
      myocardial infarction (MI) by CoQ10 supplementation. PATIENTS AND METHODS: In
      this randomized double-blinded controlled clinical trial, 52 Iranian patients
      with hyperlipidemia and MI were recruited to examine the effect of CoQ10 on serum
      total cholesterol (TC), LDL-C, HDL-C, triglyceride (TG), LDL-C/HDL-C ratio,
      TC/HDL-C ratio, fibrinogen, systolic blood pressure (SBP) and diastolic blood
      pressure (DBP). Individuals were randomly allocated to two groups for receiving
      either 200 mg/d of CoQ10 or placebo for 12 weeks. RESULTS: There were not
      significant differences in serum LDL-C (2.70 +/- 0.31 vs. 2.70 +/- 0.35 mmol/L),
      TC (4.47 +/- 0.33 vs. 4.93 +/- 0.57 mmol/L), TG (2.48 +/- 0.12 vs. 2.25 +/- 0.69
      mmol/L), and fibrinogen (2.08 +/- 0.99 vs. 38.7 +/- 0.64 mg/dL) between CoQ10 and
      placebo groups. After 12 weeks, a significant enhancement in serum HDL-C (1.44 +/
      0.18 vs. 1.14 +/- 0.18 mmol/L) level was observed between groups after the
      supplementation (P < 0.001). A significant reduction of TC, LDL-C, and fibrinogen
      and a significant increase in HDL-C concentration was observed in CoQ10 group
      after intervention (P < 0.001). Our assessment demonstrated statistically
      significant differences between the two groups in SBP and DBP after intervention
      (P < 0.001). ANCOVA also revealed significant differences in the ratio of LDL
      C/HDL-C and TC/HDL-C between the two groups (1.89 +/- 0.42 vs. 2.39 +/- 0.38, P =
      0.002; and 3.2 +/- 0.5 vs. 4.24 +/- 0.66, P = 0.01, respectively). A significant
      reduction of LDL-C/HDL-C and TC/HDL-C was observed in CoQ10 group (P < 0.001).
      CONCLUSIONS: Twelve-week supplementation with CoQ10 in patients with
      hyperlipidemia and MI can improve blood pressure, serum HDL-C as well as LDL
      C/HDL-C and TC/HDL-C ratios; therefore, it might decrease the risk of frequent
      MI.

PMID- 25763202
TI  - Medication errors of nurses and factors in refusal to report medication errors
      among nurses in a teaching medical center of iran in 2012.
AB  - BACKGROUND: About one third of unwanted reported medication consequences are due
      to medication errors, resulting in one-fifth of hospital injuries. OBJECTIVES:
      The aim of this study was determined formal and informal medication errors of
      nurses and the level of importance of factors in refusal to report medication
      errors among nurses. PATIENTS AND METHODS: The cross-sectional study was done on
      the nursing staff of Shohada Tajrish Hospital, Tehran, Iran in 2012. The data was
      gathered through a questionnaire, made by the researchers. The questionnaires'
      face and content validity was confirmed by experts and for measuring its
      reliability test-retest was used. The data was analyzed by descriptive
      statistics. We used SPSS for related statistical analyses. RESULTS: The most
      important factors in refusal to report medication errors respectively were: lack
      of medication error recording and reporting system in the hospital (3.3%), non
      significant error reporting to hospital authorities and lack of appropriate
      feedback (3.1%), and lack of a clear definition for a medication error (3%).
      There were both formal and informal reporting of medication errors in this study.
      CONCLUSIONS: Factors pertaining to management in hospitals as well as the fear of
      the consequences of reporting are two broad fields among the factors that make
      nurses not report their medication errors. In this regard, providing enough
      education to nurses, boosting the job security for nurses, management support and
      revising related processes and definitions are some factors that can help
      decreasing medication errors and increasing their report in case of occurrence.

PMID- 25763203
TI  - Epidemiological and cost analysis of self-poisoning cases in ankara, Turkey.
AB  - BACKGROUND: Poisoning is a global public health problem. Self-poisoning has
      potentially serious consequences. Follow-up studies have found that 3-10% of self
      harm patients eventually succeed. OBJECTIVES: This study was designed to
      investigate the epidemiological, clinical and economical aspects of deliberate
      self-poisoning patients admitted to Yenimahalle State Hospital Intensive Care
      Unit. PATIENTS AND METHODS: The study was carried out retrospectively in Ankara
      Yenimahalle State Hospital. It included Seventy-one patients over 16 years of age
      who were admitted to the hospital due to poisoning during 2012. Exposed poisons
      were classified into one of three categories; pharmaceuticals, pesticides, and
      alcohols. Cost account was based on the medical invoices at patient discharge.
      Data were compared using Student's T test and chi-square test. A P value of less
      than 0.05 was considered significant. RESULTS: The female/male ratio was 2.55.
      The mean age of the 71 poisoned patients was 28.92 +/- 11.51 years. Most of the
      poisoning agents were pharmaceuticals (68 cases). Among the pharmaceuticals,
      antidepressants were involved most often, followed by analgesics. There was no
      statistically significant difference between pharmaceutical agents in terms of
      hospital cost (P > 0.05). The mean length of hospital stay was 6.4 +/- 4.3 days.
      There was a statistically significant difference between the lengths of stay of
      patients in terms of hospital cost (P < 0.05). CONCLUSIONS: The patient cost
      increased as the length of stay increased due to the policy of bundle pricing.

PMID- 25763206
TI  - Predictors of anxiety and depression among women with vaginal bleeding referred
      to gynecology clinic during hajj 2011.
AB  - BACKGROUND: One of the most important complications for women during hajj trip is
      menstruation and most commonly spotting, which is the second important problem.
      This complication would cause some problems in performing religious rites as the
      main purpose of the trip and on the other hand, it would lead to psychologic
      complications for women. Controlling psychologic complications of women during
      and after hajj is necessary. OBJECTIVES: The purpose to this study was to
      investigate predictors of anxiety and depression among the women with vaginal
      bleeding who were referred to Iranian clinic in Mecca and Medina in hajj 2011.
      PATIENTS AND METHODS: In this cross-sectional study, 110 women with vaginal
      bleeding who were referred to gynecology clinic were enrolled. The Samples were
      selected by easy way method from all referrals on Tuesdays during hajj (October
      and November 2011). To evaluate the anxiety and depression signs, Hospital
      Anxiety and Depression Scale (HADS) questionnaire was employed. The analyses were
      performed using SPSS 17.0 through parametric methods. RESULTS: Predictors of
      anxiety were observed in 22 women (20%). Moreover, 34 women (30.9%) were
      diagnosed from normal to abnormal, 3 (2.72%) had depression signs, and 22 (20%)
      showed symptoms of borderline symptoms of depression. CONCLUSIONS: Considering
      the high frequency of anxiety disorder among women with vaginal bleeding in hajj,
      gynecological consultation seems essential for women during Hajj.

PMID- 25763204
TI  - The Association of Coagulation Factor V (Leiden) and Factor II (Prothrombin)
      Mutations With Stroke.
AB  - BACKGROUND: Epidemiological studies indicate that over the past forty years, the
      stroke incidence rates has increased. Factors V and II mutations are established
      genetic-variant risk factors for venous thrombosis; however, their contribution
      to stroke is a controversial issue. OBJECTIVES: This study aimed to investigate
      the potential association of FV and FII mutations with stroke in an Iranian
      population. PATIENTS AND METHODS: The study population consisted of 153 patients
      of different stroke subtypes (except cryptogenic strokes), admitted to Ghaem
      Hospital, Mashhad, Iran. The control group included 153 age- and sex-matched
      subjects without a history of cerebrovascular or neurologic diseases. Mutations
      of FV and FII were determined by using a TaqMan SNP Genotyping technique. The chi
      square and Exact Fisher tests were used to analyze the baseline characteristics.
      Results were as follows: The calculated P-value for sex and diabetes mellitus
      were 0.907 and 1.000, respectively. The case and control groups were also matched
      in low density lipoprotein (P = 0.816), high density lipoprotein (P = 0.323),
      triglyceride (P = 0.846), and total cholesterol (P = 0.079). RESULTS: Analysis of
      the FV showed that none of the study subjects were AA homozygous for this
      mutation and only 6 heterozygous subjects were detected in the case and control
      groups. Regarding FII variants, none of the study subjects were AG heterozygous
      and only 1 AA homozygous was detected in the control group. CONCLUSIONS: The
      prevalence of both FV and FII variants are population based. Iran is an
      ethnically diverse country. Therefore, for a comprehensive analysis of a
      potential association of FV and/or FII mutations with stroke among Iranian
      population, epidemiological studies could be conducted among different ethnic
      groups.

PMID- 25763207
TI  - Prevalence of dyspepsia and its associated factors among the adult population in
      southeast of iran in 2010.
AB  - BACKGROUND: Dyspepsia is a common disorder that can present many clinical
      dilemmas in patient management. Although not usually life-threatening, its
      symptoms such as abdominal pain, heartburn, early satiety and postprandial
      fullness can have a significant negative impact on patients' quality of life.
      OBJECTIVES: The aim of this study was to determine the prevalence of dyspepsia
      and its associated factors among the adult population in Kerman in 2010. PATIENTS
      AND METHODS: This cross-sectional study was performed on 2210 patients with the
      mean age of 43.4 years in Kerman, a city in southeast of Iran. Demographic
      factors, lifestyle data and gastrointestinal symptoms were collected for each
      patient. RESULTS: The prevalence of dyspepsia was 16.1% (95% confidence interval:
      14.3-18.1). The prevalence in patients with abdominal obesity (7.3%) was lower in
      comparison with those with low physical activity (13.8%). Out of other psycho
      behavioral risk factors, anxiety after controlling for other variables increased
      the risk of functional dyspepsia more than 65 percent (P = 0. 004) and depressive
      disorders also increased that risk about 2.13 percent (P < 0.0001). Patients with
      dyspepsia symptoms were more likely to restrict their diet, take herbal medicine,
      use over-the-counter drugs and consult with physicians. CONCLUSIONS: Results of
      this study reveal the moderate prevalence of dyspepsia among the adult population
      in Kerman like in other parts of the country and this prevalence is associated
      with several demographic factors, lifestyle and health-seeking behaviors.

PMID- 25763205
TI  - Gorham's Disease With Chest Wall Involvement: A Case Report and a Review of the
      Literature.
AB  - INTRODUCTION: Gorham's disease is a rare disorder characterized by osteolysis and
      abnormal vascular growth within bones. Diagnosis of Gorham's disease is often
      delayed and for accurate and early diagnosis high clinical suspicion is crucial.
      No specific treatment is available. Management options include surgery, radiation
      therapy and medical therapy. We aimed to present the first case of Gorham's
      disease with chest wall involvement in Iran. By review of the literature we
      discussed important issues of this rare disease including clinical findings,
      diagnosis and treatment options. CASE PRESENTATION: We present a 48-year-old man
      with a history of dyspnea following a blunt chest trauma who was admitted to our
      clinic several times due to reaccumulation of pleural fluid and chylothorax.
      Gorham's disease was finally established according to clinical manifestations and
      radiological findings including massive osteolysis in his left ribs and also
      histological examination. DISCUSSION: According to review of the literature and
      considering all treatment modalities the patients was successfully treated with a
      combination of radiotherapy, pamidronate and thalidomide. We suggest that this
      disease should be considered among differential diagnoses of patients with chest
      pain, pleural effusion and/or chylothorax with an unknown reason and more
      importantly history of chest trauma. In suspected cases, it is essential to
      examine biopsy specimens of the bone adjacent to the inflammated tissues in order
      to confirm diagnosis.

PMID- 25763208
TI  - Intravitreal clindamycin in the treatment of unresponsive zone one toxoplasmic
      chorioretinitis: a case report.
AB  - INTRODUCTION: The current study aimed to report a case of toxoplasma
      chorioretinitis resistant to standard treatments that dramatically responded to
      intravitreal clindamycin injection. CASE PRESENTATION: A 23-year-old woman with
      the diagnosis of ocular toxoplasmosis in the left eye was initially treated by
      oral pyrimethamine, sulfadiazine, azithromycin and oral prednisolone. Since the
      treatment was unsuccessful intravitreal clindamycin (1 mg/ 0.1 mL) was injected.
      Responding dramatically, visual acuity improved from hand motion to 20/60 and
      20/20, after seven days and six weeks, respectively. Anterior chamber and
      vitreous reactions were resolved. CONCLUSIONS: Intravitreal injection of
      clindamycin may be an acceptable alternative to the classic treatment in cases
      with refractory ocular toxoplasmosis. It may offer the patient more convenience,
      a safer systemic side effect profile, greater availability, and fewer follow-up
      visits and hematologic evaluations. Moreover, since it responds dramatically, it
      would be helpful in cases with involvement of macula or closeness to the optic
      nerve.

PMID- 25763209
TI  - Overexpression of HER2/neu as a Prognostic Value in Iranian Women With Early
      Stage Breast Cancer; A Single Institute Study.
AB  - BACKGROUND: Patients with early stage breast cancer with same treatment strategy
      can have markedly different outcomes. Human epidermal growth factor receptor 2
      (HER2/nue) gene amplification or the subsequent overexpression of protein has
      been proved to be associated with patient's outcome and response to anthracyclins
      based regimens. OBJECTIVES: This study assessed prognostic value of HER2/nue
      marker in patients with early stage breast cancer who received adjuvant
      chemotherapy with anthracyclins-based regimens. MATERIALS AND METHODS: Fifty
      tissue samples from patients with primary breast cancer of moderate risk
      receiving sequential adjuvant chemotherapy with anthracyclins-based regimens were
      assessed to evaluate HER2/nue gene status (quantified by Immunohistochemistry and
      fluorescence in situ hybridization) retrospectively. Besides, correlation of
      HER2/neu with patients' characteristics and outcome was studied. RESULTS:
      HER2/neu amplification was identified in 19 (38%) of 50 patients. No significant
      difference regarding HER2/neu status was seen in clinic pathological
      characteristics of patients. Although Progression Free Survival (PFS) was shorter
      in HER2 overexpressed group, but uni/multivariate analysis adjusted for HER2
      overexpression, nodal involvement, hormone receptor status, age and tumor size
      revealed no significant predictive and/or prognostic value for HER2 regarding
      PFS. CONCLUSIONS: This study on a limited number of patients treated with
      adjutant anthracyclins-based regimens, revealed that HER2/neu is not a unique
      strong predictor for outcome, thus according to combination of HER2/neu status
      and other clinical factors, it is necessary to distinguish patients at high risk
      of recurrence.

PMID- 25763210
TI  - The diagnostic accuracy of purple line in prediction of labor progress in
      omolbanin hospital, iran.
AB  - BACKGROUND: Currently, vaginal examination is the gold standard for assessment of
      labor progress. The World Health Organization emphasizes that the number of
      vaginal examinations should be limited where it is necessary. OBJECTIVES:
      Therefore, this study aimed to determine the diagnostic accuracy of purple line
      in the prediction of labor progress. PATIENTS AND METHODS: In this cross
      sectional study, 350 women with a single pregnancy in vertex presentation and
      gestational age of 38-42 weeks without any medical disorder, admitted to
      government hospitals of Mashhad, were selected using convenience sampling.
      Vaginal examination and observation of the line each hour in the active phase of
      labor were measured. Abnormal progress of labor was defined as cervical
      dilatation less than 1 centimeter/hour in the active phase for two consecutive
      hours and fetal head descend less than 1cm/h or duration of more than two hours
      for nulliparous and one hour for multiparous In the second stage of labor. Data
      was analyzed by SPSS version 16 using chi -square test. RESULTS: The purple line
      appeared in 75.3% of women during the active phase of labor. Appearance of the
      purple line in the prediction of labor progress had 90.2% sensitivity, 45.3%
      specificity, 88.1% positive predictive value, 51.0% negative predictive value in
      the first stage of labor and had 87.6% sensitivity, 52.4% specificity, 96.5%
      positive predictive value, 22.0% negative predictive value in the second stage of
      labor and has 68.57% sensitivity, 42.66% specificity, 85.32% positive predictive
      value, and 43.85% negative predictive value for the total labor. CONCLUSIONS:
      According to the appearance of the purple line in most of the cases and its high
      sensitivity and specificity, we can use it as a non-invasive complementary method
      for clinical assessment of labor progress.

PMID- 25763211
TI  - Detection of Class I Integrons in Staphyloacoccus aurous Isolated From Clinical
      Samples.
AB  - BACKGROUND: Staphylococcus aurous is a major pathogen, causing variety of
      diseases and death in Iran and in the world. Despite the use of a spectrum of new
      antibiotics, this organism has caused severe infections in burns as well as in
      different parts of the body, due to acquired drug resistance. Widespread
      inappropriate use of antibiotics in treating bacterial infections has led to the
      selection and circulation of resistant strains and the growing risk of
      transferring resistant genes to sensitive bacteria. One of the causes of
      antibiotic resistance in S. aurous strains is the gain of resistance genes
      including integrase and qac/sul1. OBJECTIVES: The purpose of this study was to
      investigate the presence of class 1 integron in S. aurous strains isolated from
      clinical samples for the first time in Iran. MATERIALS AND METHODS: This
      descriptive study was performed on 200 strains of S. aurous isolated from
      patients admitted to Baqiyatallah Hospital in Tehran in 2013. These strains were
      confirmed using biochemical and serological tests and the presence of class 1
      integron was determined by polymerase chain reaction (PCR). RESULTS: Among the
      200 samples, 1% of the strains (two isolates) contained the class 1 integron
      gene. The results of this study showed that the highest frequency of the obtained
      samples belonged to males and the isolates occurred mostly in individuals aged 51
      60 years old. The highest number of strains was found in wound samples. The
      strains were most frequently isolated from the emergency ward and the intensive
      care unit (ICU). CONCLUSIONS: Findings of this study showed that integron can
      have a limited frequency in S. aurous isolated from clinical sample in Tehran.

PMID- 25763212
TI  - Antecedents and consequences of work engagement among nurses.
AB  - BACKGROUND: Engaged nurses have high levels of energy and are enthusiastic about
      their work which impacts quality of health care services. However, in the context
      of Iran, due to observed burnout, work engagement among nurses necessitates
      immediate exploration. OBJECTIVES: This investigation aimed to identify a
      suitable work engagement model in nursing profession in hospitals according to
      the hypothesized model and to determine antecedents and consequences related to
      work engagement among nurses. PATIENTS AND METHODS: In this cross-sectional
      study, a questionnaire was given to 279 randomly-selected nurses working in two
      general teaching hospitals of Shiraz University of Medical Sciences (Shiraz,
      Iran) to measure antecedents and consequences of work engagement using the Saks's
      (2005) model. Structural Equation Modeling was used to examine the model fitness.
      RESULTS: Two paths were added using LISREL software. The resulting model showed
      good fitness indices (chi(2) = 23.62, AGFI = 0.93, CFI = 0.97, RMSEA = 0.07) and
      all the coefficients of the paths were significant (t >= 2, t <= -2). A
      significant correlation was found between work engagement and model variables.
      CONCLUSIONS: Paying adequate attention to the antecedents of work engagement can
      enhance the quality of performance among nurses. Additionally, rewards,
      organizational and supervisory supports, and job characteristics should be taken
      into consideration to establish work engagement among nurses. Further researches
      are required to identify other probable antecedents and consequences of nursing
      work engagement, which might be related to specific cultural settings.

PMID- 25763213
TI  - Empowerment needs of women with breast cancer: a qualitative study.
AB  - BACKGROUND: Due to the increasing number of women suffering from breast cancer
      worldwide, promoting the empowerment of these patients is an important factor
      affecting their survival. OBJECTIVES: Few studies have investigated the
      empowerment needs of the breast cancer women, especially in Iran. Therefore, this
      study was performed to explain the empowerment needs of women with breast cancer
      in Iran. PATIENTS AND METHODS: In this qualitative study, 19 women with breast
      cancer were interviewed regarding their empowerment needs using the individual
      open-ended and, in-depth interviews and then the qualitative data were analyzed
      through content analysis. RESULTS: Three main categories of empowerment needs
      from the participants' perspectives were as follows: 1- information: the initial
      empowerment plans (timely and comprehensive information, coordination and
      continuity of information, easy and full-time access to information), 2- beliefs:
      the approval of the empowerment plans for execution (actuality, trust and hope
      and new beliefs), and 3- skills: efficient execution of the empowerment plans
      (communication skills, expression the needs, emotions, questions and use of the
      internet). CONCLUSIONS: It seems that promoting the empowerment of women with
      breast cancer is essential. Factors found in this study and also in similar
      studies, in which empowerment needs are explained in-depth through the
      experiences of the patients, should be considered and used in the treatment,
      educational and counseling programs to promote the empowerment of women with
      breast cancer.

PMID- 25763214
TI  - Angina self-management plan and quality of life, anxiety and depression in post
      coronary angioplasty patients.
AB  - BACKGROUND: Coronary artery diseases are the most frequent cause of mortality in
      industrialized countries as well as Iran. Coronary artery disease affects
      patient's quality of life (QoL) and produces some degrees of anxiety and
      depression. Although self-management programs have shown significant impact on
      chronic diseases, there is limited evidence in Iran regarding the effectiveness
      of these interventions, particularly in patients with coronary artery disease.
      OBJECTIVES: This study aimed to evaluate the effects of angina plan on QoL,
      anxiety, and depression in post coronary angioplasty patients referred to
      selected hospitals in Shiraz. PATIENTS AND METHODS: This parallel randomized,
      controlled trial was conducted in selected hospitals in Shiraz, Iran. We enrolled
      80 post coronary angioplasty eligible patients in the study. After acquisition of
      the informed consent, eligible patients were randomly divided into two groups:
      control and experimental. Pretest data were obtained by using a demographic data
      form and two valid and reliable questionnaires for QoL, anxiety, and depression.
      Blood pressure, weight, and height (to calculate body mass index) were measured
      too. Patient's history of smoking, diabetes, hypercholesterolemia, hypertension,
      and coronary vascular involvement (with grade and severity) were obtained from
      their medical records. A 12-week angina plan intervention consisted of a 30 to 40
      minutes of counseling interview and telephone follow up at the end of 1, 4, 8,
      and 12 weeks were performed for experimental group. Post-test data were obtained
      three months after the pretest using the same questionnaires as pretest. QoL data
      were analyzed by analysis of co-variance (ANCOVA). The results (before and after
      intervention) regarding anxiety and depression were analyzed by independent t
      tests or their equivalent nonparametric Mann-Whitney test using SPSS v. 11.5.
      RESULTS: There was no statistically significant difference in demographic
      variables between two groups. Baseline mean scores for QoL, anxiety, and
      depression did not differ between the two groups. There was a significant
      difference between the experimental and control groups in terms of changes in
      perception of QoL before and after the intervention. Adjusted mean +/- SD of
      perception of QoL for the control group was 38.48 +/- 13.38 and for the
      experimental one was 56.30 +/- 13.38, with a P value of less than 0.001. The mean
      difference of anxiety scores (before and after intervention) in experimental and
      control groups were 1.15 +/- 1.99 and-.0.07 +/- 2.22, respectively with a P value
      of less than 0.01. The mean difference of depression scores (before and after
      intervention) in experimental and control groups were 0.4 +/- 2.89 and 0.13 +/-
      2.76, respectively (P > 0.05). CONCLUSIONS: Our results show that the self
      management angina plan was effective in improving perception of QoL and reducing
      anxiety. Further studies with a larger sample size and a longer follow-up period
      are recommended to better understand the effectiveness of this plan.

PMID- 25763215
TI  - Cloning of the Recombinant Cytochrome P450 Cyp141 Protein of Mycobacterium
      tuberculosis as a Diagnostic Target and Vaccine Candidate.
AB  - BACKGROUND: Tuberculosis has been announced as a global emergency by World Health
      Organization and the second infectious agent of mortality worldwide. The general
      policy in the development of new vaccines is to develop some vaccines with higher
      efficiency not only for infants but also for adults compared with the Bacillus
      Calmette-Guerin vaccine. Recently, cytochrome P450 cyp141 has been introduced as
      a new target for detecting Mycobacterium tuberculosis from clinical samples.
      OBJECTIVES: The aim of this study was to clone this gene in order to pave the way
      for more evaluation. MATERIALS AND METHODS: M. tuberculosis H37Rv DNA was
      extracted by a standard phenol-chlorophorm protocol. After designing the specific
      primers, P450 cyp141 gene was replicated by PCR. The purified PCR products were
      then subcloned into the pTZ57R/T plasmid vector. After extraction, enzyme
      digestion, and recombinant pTZ57R/T-cyp141 plasmid vector sequencing, the
      aforementioned products were cloned into a pET-26b plasmid vector. Then, the
      recombinant pET26b-cyp141 plasmid molecules were transformed to Escherichia coli
      strain BL21 (DE3) using the transformation method. Next, the recombinant pET26b
      cyp141 plasmids were purified and evaluated by the enzyme digestion analysis.
      RESULTS: The cloning of P450 cyp141 gene was confirmed by the enzyme digestion
      and sequencing of the recombinant pTZ57R/T-cyp141 and pET26b-cyp141 plasmid
      vectors. CONCLUSIONS: The results of this study demonstrated that the P450 cyp141
      gene was successfully cloned into a pET26b plasmid vector as an expression
      vector. In this paper, for the first time in Iran, this gene was cloned for more
      purposes, including the expression and purification of the recombinant cytochrome
      P450 cyp141 protein.

PMID- 25763216
TI  - Evaluation of Helicobacter pylori vacA and cagA Genotypes and Correlation With
      Clinical Outcome in Patients With Dyspepsia in Hamadan Province, Iran.
AB  - BACKGROUND: Helicobacter pylori is known to be a causative agent of chronic
      active gastritis, peptic ulcer and gastric cancer in human. Diverse genotypes of
      H. pylori strains have different virulence potency and geographic distribution.
      OBJECTIVES: The purpose of this study was to investigate the association between
      the cytotoxin-associated gene (cagA), and the various vacuolating cytotoxin
      (vacA) genotypes of H. pylori strains and clinical outcomes in patients referred
      to Shahid-Beheshti Hospital in Hamadan, Iran. PATIENTS AND METHODS: In this cross
      sectional study, biopsy samples were collected consecutively from 153 patients
      with gastric cancer (GC), peptic ulcer dyspepsia (PUD) and non-ulcer dyspepsia
      (NUD) in the gastroenterology department of Shahid-Beheshti Hospital in Hamadan
      province, the west of Iran. H. pylori infection was confirmed in 83 patients (3
      with GC, 27 with PUD, and 53 with NUD) by histology, rapid urease test (RUT) and
      culture. Genomic DNA was extracted from the bacterial isolate and was further
      confirmed with 16S rRNA gene sequencing as H. pylori, and characterized based on
      cagA and vacA genotyping using the polymerase chain reaction (PCR) method.
      RESULTS: In this study, vacA genotypes s1/m2, s1/m1, s2/m2 and s2/m1 were
      determined in 43.4%, 19.3%, 13.2% and 6% of the isolated H. pylori, respectively.
      The vacAs1 genotype was detected in 52 (62.6%) isolates, of which the vacAs1a
      genotype was detected in 45.2, 40.7, and 66.6% of the isolates from patients with
      NUD, PUD, and GC, respectively. The cagA-positive genotype was determined in 73
      (87.9%) isolates and 10 (12.1%) were negative. The frequency rates of cagA gene
      were 84.9, 92.6 and 100% in isolates of patients with NUD, PUD, and GC,
      respectively. The cagA-positive genotype is strongly associated with s1a/m2 and
      s1a/m1 vacA genotypes. CONCLUSIONS: The most predominant VacA genotypes in our
      areas were s1/m2 and s1/m1, which regard as the genotypes with more virulence
      intensity. The H. pylori vacAs1a, cagA genotypes have a significant relationship
      with the presence of PUD and GC in Iranian patients with dyspepsia.

PMID- 25763218
TI  - Functional rudimentary horn as a rare cause of pelvic pain: a case report.
AB  - INTRODUCTION: Pelvic pain results from many causes such as primary dysmenorrhea,
      uterine anomalies, menstrual outflow obstruction, endometriosis, myoma and
      adenomyosis. This study reports on a rare case of non-communicating functional
      rudimentary horn. CASE PRESENTATIONS: A 15-year-old nulligravida young woman with
      a history of severe intermittent pelvic pain presented a 4-5 centimeter mass. A
      surgical procedure for appendicitis was previously performed on this patient. Per
      operative diagnosis was myoma and suspicion of leismus sarcoma. Laparotomy
      revealed left rudimentary horn, non-communication was confirmed by postoperative
      hysterosalpingogram (HSG) and magnetic resonance imaging (MRI). Resection of mass
      and left fallopian tube was done during the second surgery. CONCLUSIONS:
      Rudimentary horn should be considered in differentiation of pelvic pain and mass
      in young females. Early diagnosis and horn resection prevents emergency surgery
      and reliefs pain.

PMID- 25763217
TI  - Cardiopulmonary safety of propofol versus midazolam/meperidine sedation for
      colonoscopy: a prospective, randomized, double-blinded study.
AB  - BACKGROUND: Different levels of pharmacological sedation ranging from minimal to
      general anesthesia are often used to increase patient tolerance for a successful
      colonoscopy. However, sedation increases the risk of respiratory depression and
      cardiovascular complications during colonoscopy. OBJECTIVES: We aimed to compare
      the propofol and midazolam/meperidine sedation methods for colonoscopy procedures
      with respect to cardiopulmonary safety, procedure-related times, and patient
      satisfaction. PATIENTS AND METHODS: This was a prospective, randomized, double
      blinded study, in which 124 consecutive patients undergoing elective outpatient
      diagnostic colonoscopies were divided into propofol and midazolam/meperidine
      sedation groups (n: 62, m/f ratio: 26/36, mean age: 46 +/- 15 for the propofol
      group; n: 62, m/f ratio: 28/34, mean age: 49 +/- 15 for the midazolam/meperidine
      group) by computer-generated randomization. The frequency of cardiopulmonary
      events (hypotension, bradycardia, hypoxemia), procedure-related times (duration
      of colonoscopy, time to cecal intubation, time to ileal intubation, awakening
      time, and time to hospital discharge) and patients' evaluation results (pain
      assessment, quality of sedation, and recollection of procedure) were compared
      between the groups. RESULTS: There were no statistically significant differences
      between the two groups with respect to demographic and clinical characteristics
      of the patients, the frequency of hypotension, hypoxemia or bradycardia, cecal
      and ileal intubation times, and the duration of colonoscopy. The logistic
      regression analysis indicated that the development of cardiopulmonary events was
      not associated with the sedative agent used or the characteristics of the
      patients. The time required for the patient to be fully awake and the time to
      hospital discharge was significantly longer in the propofol group (11 +/- 8 and
      37 +/- 11 minutes, respectively) than the midazolam/meperidine group (8 +/- 6 and
      29 +/- 12 minutes, respectively) (P = 0.009 and P < 0.001, respectively). The
      patient satisfaction rates were not significantly different between the groups;
      however, patients in the propofol group experienced more pain than patients in
      the midazolam/meperidine group (VAS score: 0.31 +/- 0.76 vs. 0 +/- 0; P = 0.002).
      CONCLUSIONS: Midazolam/meperidine and propofol sedation for colonoscopy have
      similar cardiopulmonary safety profiles and patient satisfaction levels.
      Midazolam/meperidine can be preferred to propofol sedation due to a shorter
      hospital length of stay and better analgesic activity.

PMID- 25763219
TI  - Zolpidem dependency and withdrawal seizure: a case report study.
AB  - INTRODUCTION: Zolpidem is a short acting inducer of sleep and thought to lack
      benzodiazepine properties such as anxiolysis, anticonvulsion, muscle relaxation
      and side effects such as dependency. Recently, some cases of Zolpidem abuse and
      dependency have been reported. In review of literature, we found that the lowest
      reported dosage of Zolpidem, which caused dependency, was 160 mg daily. CASE
      PRESENTATION: We reported a 30-year-old unmarried Iranian woman with dysthymic
      disorder and chronic insomnia treated with Zolpidem irregularly. She started to
      use Zolpidem with 5mg per day irregularly since a year ago but augmented its
      daily dosage gradually to 100 to 150 mg per day in divided doses. After a period
      of 16 hours without taking Zolpidem she developed a withdrawal syndrome, with
      generalized tonic-clonic seizures for two times. She was managed with supportive
      care and recovered completely. CONCLUSIONS: Zolpidem dependency and withdrawal
      seizure can occur with a dosage under last reported doses. Therefore, possibility
      of mentioned problems cannot be excluded at any dosage and physicians should pay
      more attention to potential of Zolpidem to create these adverse effects.

PMID- 25763220
TI  - Effects of Educational Intervention on Health-Promoting Lifestyle and Health
      Related Life quality of Methamphetamine Users and Their Families: a Randomized
      Clinical Trial.
AB  - BACKGROUND: Family-centered empowerment of drug and stimulant users is an
      effective program for a better response to treatment, prevention of treatment
      adverse effects, and promotion quality of life (QoL) and lifestyle in the process
      of discontinuing drug abuse. OBJECTIVES: This study aimed to determine the
      effects of educational intervention, based on family-centered empowerment and
      Pender's health promotion models, on health-promoting lifestyle and health
      related QoL among methamphetamine users and their families. PATIENTS AND METHODS:
      In a randomized clinical trial, methamphetamine users, who were admitted to
      Tehran University of Medical Sciences Substance Abuse Treatment Centers, were
      randomly allocated to three groups: a group for training of methamphetamine users
      who were in recovery phase (intervention group 1;95 subjects);a group for
      training of a family member of methamphetamine users who were in recovery phase
      (intervention group 2; 95 subjects); and a control group (95 subjects). A
      demographic checklist and a standard questionnaire covering health-promoting
      lifestyle, health-related QoL, self-efficacy, perceived affect, perceived social
      support, and perceived barriers dimensions were used to gather required data.
      Independent-samples t test, paired-samples t-test, and ANCOVA were used to
      analyze the data. RESULTS: Analysis of covariance showed that after adjusting for
      effects of pretest scores, the difference between mean post-test scores of health
      promoting lifestyle scale, health-related QoL scale, and all constructs of
      Pender's health promotion model (self-efficacy, perceived affect, perceived
      social support, and perceived barriers) in the intervention group 1 and control
      group were significant (P< 0.0001). In addition, changes in mean scores of
      lifestyle scale (42.4 +/- 13.6), QoL scale (29.1 +/- 14.2), self-efficacy (16.1
      +/- 2.6), perceived affect (16.1 +/- 8), social support (35.4 +/- 12.4), and
      barriers (17.2 +/- 15.8) before and after intervention were significant in the
      intervention group 2 (P < 0.0001). CONCLUSIONS: Application of family-centered
      empowerment model among methamphetamine users and their families is practically
      feasible and can result in enhancement and improvement of their QoL, lifestyle,
      and health promotion model constructs.

PMID- 25763221
TI  - Vasopressin and prevention of hypotension during hemodialysis.
AB  - CONTEXT: The occurrence of intradialytic hypotension (IDH) during hemodialysis
      (HD) continues to be a main problem in patients with ESRD (end-stage kidney
      disease). It also negatively affects health-related quality of life. We aimed to
      determine vasopressin effect in decreasing IDH. EVIDENCE ACQUISITION: We reviewed
      clinical and experimental literature in a variety of sources, including PubMed,
      Current Content, Scopus, Embase, and Iranmedex regarding the possible effect of
      vasopressin administration in prevention of hypotension during HD to clarify its
      mechanism, efficacy, and safety. RESULTS: Although arginine vasopressin is widely
      recognized for its anti-diuretic properties, it is also a well-recognized
      vasoconstrictor. It has been shown that the vasopressin release (as it would
      normally be expected) does not increase in the majority of HD patients with
      recurrent dialysis hypotension. In addition, it has also been reported that
      vasopressin secretion (due to the osmotic stimulation) is the most important
      mechanism in blood pressure control in ESRD patients receiving hypertonic
      solution for IDH. Therefore, it is suggested that vasopressin administration may
      improve hemodynamic stability among ESRD patients during HD. There are few
      clinical trials about this issue, suggesting that administration of exogenous
      vasopressin may be significantly associated with a decreased incidence of IDH as
      well as cardiovascular stability in ESRD patients in need of volume removal
      during HD. CONCLUSIONS: Vasopressin insufficiency may have an important role in
      the pathogenesis of hemodynamic instability during HD and administration of
      exogenous vasopressin is significantly associated with a lower incidence of IDH.

PMID- 25763222
TI  - The association of physical access with the interval between attending the
      hospital and receiving service in emergency department.
AB  - BACKGROUND: The relation between physical access in emergency department (ED) and
      the time patients have to wait before being served is unknown. OBJECTIVES: Our
      objective was to discover the associations between the physical access in ED and
      the time patients had to wait before receiving services. MATERIALS AND METHODS:
      In this cross-sectional study, statistical society comprised two portions,
      namely, public hospitals' EDs and referred patients to the ward. Data on waiting
      time for 240 patients in six public and private hospitals were gathered. In
      addition, physical condition of EDs was inspected by visiting these hospitals. A
      designed checklist, based on the introduced physical space, was filled for each
      hospital. Results of the checklist were scored using Likert's five-points scale
      and Spearman and Pearson's correlation coefficient were applied to determine the
      relationship between physical access and waiting time. RESULTS: The correlation
      between the waiting time beginning from the very moment of stepping into the ward
      until first examination and physical condition at the triage wards in private (P
      < 0.001) and public hospitals (P > 0.05) was not significant. The waiting
      interval, beginning from the very moment of stepping into the ward until first
      examination and access to physical space of ED, was significant for private
      hospitals (P < 0.001) and insignificant for public hospitals (P > 0.05).
      CONCLUSIONS: According to the results, there was a direct correlation between
      access to physical space in ED and waiting time. In addition, improving the
      physical access did not necessarily result in shorter waiting time. Therefore, to
      improve triage process, improvement of waiting time indices, and modifying forms
      of work process in ED are recommended.

PMID- 25763223
TI  - Comparison of plasma oxidative biomarkers and conformational modifications of
      hemoglobin in patients with diabetes on hemodialysis.
AB  - BACKGROUND: Diabetes is associated with an increased generation of reactive
      oxygen species (ROS), which plays an important role in the development of
      oxidative stress and anemia. OBJECTIVES: The main purpose of this study was to
      investigate whether patients with diabetes undergoing hemodialysis (HD) were
      susceptible to oxidative stress and whether resulting damages affect the
      structure of hemoglobin (Hb) and plasma proteins. PATIENTS AND METHODS: Twenty
      patients with diabetes undergoing HD, 20 patients with diabetes and normal renal
      function, and 20 age- and sex-matched healthy subjects were included in this
      study. Methaemoglobin (Met-Hb), hemichrome and conformational changes of Hb were
      analyzed as oxidative markers in erythrocytes. Ferric reducing ability of plasma
      (FRAP) and protein carbonyl content (PCO) were determined as plasma oxidative
      biomarkers. Also triglyceride, cholesterol, albumin, blood urea nitrogen (BUN),
      creatinine, glucose and uric acid were assayed as biochemical parameters of
      plasma. RESULTS: Patients with diabetes undergoing hemodialysis had significantly
      lower levels of PCO and albumin (P < 0.05), but significantly higher levels of
      FRAP, BUN, creatinine and uric acid (P < 0.05) as compared to patients with
      diabetes and normal renal function. Linear regression analysis showed significant
      negative correlations between PCO and FRAP (r = -0.53), oxy-Hb (r = -0.88) and Hb
      absorbance at 340 nm (r = -0.79), 420 nm (r = -0.85) and 577 nm (r = -0.68) in
      patients with diabetes undergoing hemodialysis. Also PCO was significantly and
      positively correlated with Hb absorbance at 275 nm (r = 0.63) and 560 nm (r =
      0.61) which confirmed the oxidative damage to erythrocytes in control subjects.
      CONCLUSIONS: Hemodialysis exacerbates oxidative stress and conformational changes
      of Hb in patients with diabetes on hemodialysis. The FRAP value can be used as a
      positive determinant, while PCO and Hb derivatives can be used as negative
      determinants of oxidative stress in patients with diabetes.

PMID- 25763224
TI  - Preventive effect of intrathecal paracetamol on spinal cord injury in rats.
AB  - BACKGROUND: Ischemic injury of the spinal cord during the surgical repair of
      thoracoabdominal aortic aneurysms might lead to paraplegia. Although a number of
      different mechanisms have been proposed, the exact cause of paraplegia has
      remained unknown, hampering the development of effective pharmacologic or other
      strategies for prevention of this condition. A number of studies suggested that
      cyclooxygenases (COX) contribute to neural breakdown; thus, COX inhibitors might
      reduce injury. OBJECTIVES: We aimed to assess the preventive effect of
      intrathecal (IT) pretreatment with paracetamol on spinal cord injury in a rat
      model. MATERIALS AND METHODS: This experimental study was performed in Ataturk
      University Animal Research Laboratory Center, Erzurum, Turkey. Adult male Wistar
      rats were randomly allocated to three experimental groups (n = 6) to receive IT
      physiologic saline (controls), 50 ug of paracetamol, or 100 ug paracetamol one
      hour before induction of spinal cord ischemia. Six other rats were considered as
      the sham group. For the assessment of ischemic injury, motor functions of the
      hind limbs and histopathologic changes of the lumbar spinal cord were evaluated.
      Additional 20 rats were divided into two equal groups for the second part of the
      study where the survival rates were recorded in controls and in animals receiving
      100 ug of paracetamol during the 28-day observation period. RESULTS: Pretreatment
      with 100 ug of paracetamol resulted in a significant improvement in motor
      functions and histopathologic findings (P < 0.05). Despite a higher rate of
      survival in 100 ug of paracetamol group (70%) at day 28, the difference was not
      statistically significant in comparison with controls. CONCLUSIONS: Our results
      suggest a protective effect of pretreatment with IT paracetamol on ischemic
      spinal cord injury during thoracolumbar aortic aneurysm surgery.

PMID- 25763225
TI  - ZAP70 Expression Within del6q21, del11q13 and del17p13 Cytogenetic Subgroups of
      Iranian Patients with Chronic Lymphocytic Leukemia.
AB  - BACKGROUND: B-cell chronic lymphocytic leukemia (B-CLL) is the most common form
      of leukemia in adults. Some reports showed that expression of ZAP70 gene and
      chromosomal abnormality are two prognostic factors in management of B-CLL.
      OBJECTIVES: In this study, we determined ZAP70 mRNA expression level in the
      del17p13, del6q21 and del11q13 subgroups of Iranian B-CLL patients to investigate
      prognostic value of ZAP70 expression. PATIENTS AND METHODS: In this cross
      sectional study, fluorescence in situ hybridization analysis was carried out on
      66 Iranian B-CLL patients. Zap70 mRNA expression was evaluated by using Real Time
      RT-PCR. RESULTS: Molecular analysis showed that ZAP70 expression increased 2.46
      fold in the del11q13 subgroup, 2.87 fold in the del17p13 and 1.87 fold in the
      del6q21, compared to the 15 patients in the control group. Comparison of standard
      deviation and mean of the ZAP70 expression profile within the subgroups showed
      more variability among the cases of the del11q13 and del17p13 versus tight
      clustering for the del6q21. Therefore, there is a relation between del6q21
      aberrations; which has good prognosis with normal levels of ZAP70 expression.
      CONCLUSIONS: The results of ANOVA test showed that ZAP70 expression gene was
      significantly increased in del17p13 and del11q13 subgroups compared to control
      group. Thus, ZAP70 may play an important role in the prognosis of B-CLL patients.

PMID- 25763226
TI  - Interleukin-2 expression in lupoid and usual types of old world cutaneous
      leishmaniasis.
AB  - BACKGROUND: Interleukin (IL)-2 plays a central role in T cell-dependent immune
      responses. OBJECTIVES: We conducted this study to determine and compare IL-2
      expression in lupoid and usual types of Old World Cutaneous Leishmaniasis (OWCL),
      using immunohistochemistry. PATIENTS AND METHODS: Thirteen paraffin-embedded
      specimens of lupoid and 12 specimens of usual types of OWCL were used. A mouse
      monoclonal anti IL-2 antibody was used for staining by the envision technique.
      RESULTS: There were strongly stained discrete foci of staining through
      inflammatory infiltrates of dermis and also in basal layers of epidermis and
      adnexal structures, with a distinctive pattern of hot spot activity foci (mean of
      9.31 +/- 6.4 versus 8.17 +/- 6.9 foci per HPF for lupoid and usual types,
      respectively). The expression of IL-2 had no correlation with the pattern of
      granulomatous inflammation (tuberculoid, sarcoidal or mixed suppurative).
      CONCLUSIONS: Interleukin-2 takes part in the immunological response of the
      granulomatous reaction of OWCL and is not statistically different between lupoid
      and usual types (P = 0.674).

PMID- 25763227
TI  - Initial Presentation of HIV Infection With Two Successive Acute Arterial
      Thromboses: A Case Report.
AB  - INTRODUCTION: One of the complications of HIV infection is greater risk of
      thromboembolic events. A variety of mechanisms has been found to be responsible
      for prothrombotic tendency in patients with HIV infection. CASE PRESENTATION: A
      27-year-old heterosexual smoker man was referred to our center due to a sudden
      onset severe left lower extremity pain and claudication since three days prior to
      admission. In physical examination, end extremity coldness and discoloration as
      well as left lower extremity pulselessness were found. Color-Doppler sonography
      revealed a large thrombus in the left common iliac artery and two thrombi in the
      distal halves of both anterior and posterior tibialis arteries, so the patient
      was transferred to the operating room for proximal thrombectomy where the blood
      flow was reestablished and all pulses were then detectable. Two days later, the
      patient developed another similar episode from knee down and underwent the second
      thrombectomy. In evaluation, HIV Ab had positive result by ELISA. CONCLUSIONS:
      This case inspires consideration of HIV infection as a leading cause of
      thromboembolic event in individuals affected by the first episode of unprovoked
      one in whom diagnosis of HIV infection has not been established yet.

PMID- 25763228
TI  - Chief complaints and diagnosis of patients visited by caravan physicians during
      hajj 2010.
AB  - BACKGROUND: The primary data on the patient's status are articulated by the
      patient and consist of conditions that force the patient to seek treatment. Such
      data helps the physician effectively to make an appropriate list of differential
      diagnoses to establish a treatment protocol. OBJECTIVES: The objective of this
      study was to review the frequency of patients' chief complaints in Hajj to plan
      and develop medical protocols for expected problems in Hajj. PATIENTS AND
      METHODS: In this short-term past-oriented study, all medical files of the Hajj
      pilgrims were reviewed and all data regarding the diagnoses were extracted.
      RESULTS: In general, medical data of 107074 cases had been registered in this
      software. Cough with the frequency of 24083 (22.45%) was the most frequent
      complaints of the patients. Respiratory tract infections diseases with 66197
      persons (61.82%) were the most frequently diagnosed diseases in times of annual
      Hajj of 2010. CONCLUSIONS: Respiratory disease, musculoskeletal pain, headache,
      and digestion problems were among the most important reasons of patients'
      referral to physicians in times of Hajj. The mentioned complications could be
      prevented through correct trainings and conforming to health recommendations in
      times of Hajj.

PMID- 25763229
TI  - Stage at diagnosis and delay in seeking medical care among women with breast
      cancer, delhi, India.
AB  - BACKGROUND: Patients with cancer often delay seeking medical advice in developing
      countries. It can adversely influence the outcome of disease. OBJECTIVES: The
      present study was performed to determine the stage at diagnosis and delay in
      seeking medical care among women with breast cancer in Delhi, India. PATIENTS AND
      METHODS: This was a cross-sectional study based on a census (case series)
      approach to reach all women (172) diagnosed with primary breast cancer "detected
      in surgery Out Patient Department (OPD) from January 2007 to December 2009" at
      Lok Nayak Hospital, Delhi, India. Patients were interviewed using a self
      structure questionnaire. Seeking behavior variables were awareness of problem,
      first consultation, followed physician's advice, detection of problem, system of
      medicine and gap between knowing the problem and consultation (patient delay).
      Statistical Analysis was performed using the Microsoft SPSS-pc version 14.0
      statistical program. The analytic methods were used (mean, standard deviation,
      X(2), Fisher's Exact Test, K-S, Kruskal-Wallis) for variables. All statistical
      tests were performed at a significance level of 5% (P < 0.05). RESULTS: the mean
      age of women was 46.99 years. 38.4% of women were <= 40 years. 61% of women were
      in stage IV of cancer at the time of diagnosis. The mean duration of gap between
      knowing the problem and consulting a physician (patients delay) was 10.90 months.
      There was no significant association between stage of cancer and consultation
      gap. A significant association was found between the stage of breast cancer and
      income; women with lower income had a higher stage of breast cancer (P < 005).
      CONCLUSIONS: A significant association was found between ages of women with their
      delays in consultation. Delay is still prevalent amongst women with breast
      cancer. It seems necessary to design educating programs for women in both
      clinical and community settings, about breast cancer and early detection
      practices.

PMID- 25763230
TI  - The attitude-behavior discrepancy in medical decision making.
AB  - BACKGROUND: In medical practice, the dissatisfaction of patients about medical
      decisions made by doctors is often regarded as the fuse of doctor-patient
      conflict. However, a few studies have looked at why there are such
      dissatisfactions. OBJECTIVES: This experimental study aimed to explore the
      discrepancy between attitude and behavior within medical situations and its
      interaction with framing description. PATIENTS AND METHODS: A total of 450
      clinical undergraduates were randomly assigned to six groups and investigated
      using the classic medical decision making problem, which was described either in
      a positive or a negative frame (2) * decision making behavior?attitude to risky
      plan?attitude to conservative plan (3). RESULTS: A discrepancy between attitude
      and behavior did exist in medical situations. Regarding medical dilemmas, if the
      mortality rate was described, subjects had a significant tendency to choose a
      conservative plan (t = 3.55, P < 0.01) yet if the survival rate was described,
      there was no such preference (t = -1.48, P > 0.05). However, regardless of the
      plan chosen by the doctor, the subjects had a significant opposing attitude (P <
      .05). Framing description had a significant impact on both decision making
      behavior and attitude (t behavior = -3.24, P < 0.01;t attitude to surgery =
      4.08,P < 0.01;t attitude to radiation = -2.15,P < 0.05). CONCLUSIONS: A
      discrepancy of attitude-behavior does exist in medical situations. The framing of
      a description has an impact on medical decision-making.

PMID- 25763231
TI  - An epidemiological study of gastroesophageal reflux disease and related risk
      factors in urban population of mashhad, iran.
AB  - BACKGROUND: Gastroesophageal Reflux Disease (GERD) is a chronic and common
      disease, which is characterized by heartburn and regurgitation. In the last
      couple of decades, GERD has received much attention and studies have shown an
      increase in its prevalence. Although there have been a few studies on the
      prevalence of GERD in Iran, no study has yet been done in the northeastern part
      of the country. The aim of our study was to evaluate the prevalence of GERD and
      its risk factors in a population from Mashhad. OBJECTIVES: To evaluate the
      epidemiology of GERD based on a population study in Mashhad. PATIENTS AND
      METHODS: This was a cross sectional descriptive study conducted in 2010. In
      total, 2500 participants were selected based on cluster sampling. Modified and
      validated Mayo Clinic questionnaire for GERD was used for data collection.
      Overall, 1685 questionnaires were retrieved. Fifty-one participants were excluded
      because of pregnancies, history of abdominal surgery and being less than 18 years
      old. We analyzed data using the SPSS software version 16. Prevalence of GERD and
      significant risk factors (P value < 0.05) were determined. RESULTS: In total, 420
      participants (25.7%) had GERD symptoms. Risk factors with significant effects
      consisted of smoking, consumption of non-steroidal anti-inflammatory drugs
      (NASIDs), overeating, chronic diseases, tea and coffee consumption and GERD in
      spouse. CONCLUSIONS: The prevalence of GERD among people living in Mashhad was
      above the average prevalence in other cities of Iran. However, risk factors
      seemed to be similar to those reported by other studies.

PMID- 25763232
TI  - Double uvula in a fifty-six-year-old woman.
AB  - INTRODUCTION: Deformities of the uvula are considered as the dark area of
      otorhinolaryngology practice. This little and plain part of the human organism
      has various functions and its abnormalities might cause serious disabilities.
      CASE PRESENTATION: In our case report, we present a unique deformity of the uvula
      in a 56-year-old woman. DISCUSSION: The aim of this report was to present a very
      rare condition, unique case "polyuvula", and to review the literature regarding
      other uvula abnormalities.

PMID- 25763233
TI  - Prevalence of motor developmental disorders in children in alborz province, iran
      in 2010.
AB  - BACKGROUND: Unlike developed countries, data from the developing world regarding
      motor developmental disorders is scarce. OBJECTIVES: In the present study, we
      used the Infant Neurological International Battery (Infanib) test to determine
      the prevalence of motor impairment in 4-18 month-old infants in Alborz province,
      Iran, in 2010. PATIENTS AND METHODS: This study was a descriptive-analytic study
      performed on 6150 infants in Iran. The sample was recruited by convenience
      sampling from all 4-18 month-old children attended healthcare centers in
      different districts of Alborz province. Sampling was continued until reaching the
      desired sample size. RESULTS: The sample included 3129 boys and 3021 girls. There
      was no significant difference between the scores of girls and boys (P = 0.403).
      The number of children with motor developmental abnormality varied depending on
      the considered cut-off points. In normative cut-off points, 3.7% had motor
      disorder, whereas based on the Iranian cut-off points, it was 6.5%. CONCLUSIONS:
      Providing an early detection and intervention system is an urgent public health
      problem due to the prevalence of motor developmental delay in infants living in
      Alborz province, because it indicates that most infants had been previously
      undiagnosed and untreated.

PMID- 25763235
TI  - Barberry administration and pro-oxidant-antioxidant balance in patients with
      metabolic syndrome.
AB  - BACKGROUND: Metabolic syndrome is the constellation of several cardiometabolic
      risk factors, and is associated with a heightened risk of coronary heart disease
      (CHD). The pro-oxidant-antioxidant balance (PAB) is a measure of factors that
      promote and control oxidative stress. PAB may also be associated with the risk
      factors of CHD. OBJECTIVES: This study aimed to explore the impact of
      supplementation with barberry, a fruit rich in antioxidants, on PAB in patients
      with metabolic syndrome. PATIENTS AND METHODS: A total of 106 patients diagnosed
      with metabolic syndrome were randomized in two groups: case and control. The case
      group received three capsules of barberry and the control group received three
      capsules of placebo for 6 weeks. Serum PAB was measured in all patients before
      and after the intervention. RESULTS: There was no significant difference between
      the groups regarding their baseline PAB values (P = 0.32). A significant decrease
      in PAB was observed in the barberry group (P = 0.022), whilst there was no
      significant change in the control group (P = 0.18). The magnitude of change in
      PAB during the study was significantly greater in the case group compared to the
      control group (P = 0.01). CONCLUSIONS: Barberry supplementation reduces oxidative
      burden in patients with metabolic syndrome.

PMID- 25763234
TI  - Penile length and anogenital distance in male newborns from different Iranian
      ethnicities in golestan province.
AB  - BACKGROUND: Anogenital distance (AGD) is a feasible and accepted parameter of
      exogenous or endogenous androgens effects on development of reproductive system.
      OBJECTIVES: Since there is no report on penile length (PL) and AGD in our region,
      we investigated these parameters in male newborns in Golestan Province, Iran.
      PATIENTS AND METHODS: In this cross-sectional study, we measured stretched PL and
      AGD in term newborns from different races in Dezyani Gynecologic Hospital of
      Gorgan, Iran. We also recorded the anthropometric parameters and maternal age.
      The data was analyzed using the SPSS 14. RESULTS: Means of PL and AGD of 427
      healthy term newborns were 32.1 +/- 3.5 and 24.5 +/- 2.5 mm, respectively. There
      was a positive correlation between PL and AGD (r = 0.097, P = 0.046). According
      to their ethnicity, there were 166 Fars (38.9%), 129 Turkmen (30.2%), and 132
      Sistani (30.9%) infants with mean PL of respectively 31.8 +/- 3.9, 32.3 +/- 3.3,
      and 32.4 +/- 3.3 mm and mean AGD of respectively 25 +/- 2.5, 24.3 +/- 2.5, and 24
      +/- 2.5 mm. One Fars neonate (0.23%) had micropenis (PL = 21.3 mm). CONCLUSIONS:
      Using -2.5 standard deviations as the cutoff for micropenis, a newborn infant in
      Golestan Province with a PL of < 23.3 mm had micropenis; however, more
      investigations are needed to clarify this issue.

PMID- 25763236
TI  - An unusual mesenteric tumor 'paraganglioma': a case report.
AB  - INTRODUCTION: Paragangliomas are mostly localized in the adrenal medulla and they
      are usually pheochromocytomas, derived from the neural crest, but otherwise
      mesenteric paragangliomas are extremely rare tumors. CASE PRESENTATION: In this
      article we represent a 59-year-old female with an abdominal mass and pain due to
      mesenteric paraganglioma. CONCLUSIONS: Paragangliomas can occur as mesenteric
      tumors; usually, preoperative accurate diagnosis is not possible with imaging
      methods and precise diagnosis is possible after histological evaluation.

PMID- 25763237
TI  - Iatrogenic aspiration of custom-made keel: a case report.
AB  - INTRODUCTION: Laryngeal stenosis has various causes and treatment options.
      Endoscopic resection of the stenotic part with CO2 laser is one of the treatment
      options of laryngotracheal stenosis. Keels are useful for preventing adhesion
      formation, restenosis and web formation, which may happen during the later stage.
      They can be put in place either via the endoscopic approach or through a micro
      thyroidotomy and are held in place with a heavy suture through cricothyroid and
      thyrohyoid membranes. They are left in place for two to four weeks, and then
      removed through the endoscopic approach under general anesthetics. CASE
      PRESENTATION: We report on a case of anterior glottis stenosis with keel
      aspiration for two weeks, after endoscopic CO2 laser resection of the stenotic
      section and keel placement. The patient was admitted to our center, where
      bronchoscopy was performed and the keel was removed. A new custom-made silastic
      keel was properly placed in raw areas and fixed to the skin with suture through
      the cricothyroid and thyrohyoid membranes. The keel was removed three weeks
      later. CONCLUSIONS: Endoscopic keel placement should be done with heavy suture
      through cricothyroid and thyrohyoid membranes. Surgeons should suture the keel to
      the anterior laryngeal wall with specially designed Lichtenberger's needle
      carriers to prevent complications such as keel aspiration, adhesion formation and
      imposing a second trip under general anesthetics, which put the patient at
      increased risk. The false vocal cord microflaps, as biological keels and a
      relatively new method may replace silastic keel placement in the future.

PMID- 25763238
TI  - Exploring correlation between perceived parenting styles, early maladaptive
      schemas, and depression among women with depressive symptoms in iran and India-
      role of early maladaptive schemas as mediators and moderatos.
AB  - BACKGROUND: Many studies have reported that inadequate parental styles can
      contribute to depressive symptoms through dysfunctional cognitive styles.
      OBJECTIVES: This study aimed to investigate the association of dysfunctional
      schemas and parenting style with depression, as well as the role of maladaptive
      schemas such as moderators and mediators in Iran and India. PATIENTS AND METHODS:
      The study sample was selected randomly and consisted of 200 (age group 16-60 y)
      depressed females (mild to moderate); 100 from Tehran (Iran) and another 100 from
      Pune (India). The type of the research was causal-comparative. The data
      collection took place in hospitals and clinics in the targeted cities.
      Descriptive statistic tests and hierarchical multiple regression were executed
      (for the purpose of analyzing data) by SPSS 17. RESULTS: It was demonstrated that
      the association between parenting and depression was not moderated by early
      maladaptive schemas. On the contrary, the results supported meditational models
      in which parenting styles are associated with the cognitive schemas, and these in
      turn are related to depressive symptoms. It was also found that abandonment
      mediates the impacts of maternal style on depression in Iran. On the other hand,
      abandonment and punitiveness schemas mediated the relation between paternal style
      and depression in India. CONCLUSIONS: These findings suggest that the correlation
      between childhood experiences and depression in adulthood are mediated by
      dysfunctional schemas.

PMID- 25763239
TI  - Efficacy of Viola odorata in Treatment of Chronic Insomnia.
AB  - BACKGROUND: Insomnia is the most common sleep disorder that reduces quality of
      life. OBJECTIVES: Due to side effects of hypnotic drug and the increasing demand
      for alternative medicine substitutes, violet oil (VO) was used in this study. VO
      is a known medication in Iranian traditional medicine that induces sleep in
      insomniac patients. PATIENTS AND METHODS: This study was conducted as an
      experimental pretest-posttest evaluation on VO efficacy in 50 patients with
      chronic insomnia in Iranian Traditional Medicine Clinic of Mashhad University of
      Medical Sciences, Mashhad, Iran. Treatment consisted of intranasal drop of VO,
      two drops containing 66 mg of VO in each nostril nightly before sleeping for one
      month. All patients were asked to complete an Insomnia Severity Index (ISI)
      questionnaire before the start of the trial and after one month of treatment.
      RESULTS: Improvements in sleep and ISI scores were significantly greater in
      patients after a month receiving VO drop in comparison with before starting
      treatment (P < 0.05). A few patients reported some complications about VO
      consumption, most of which were mild and no serious adverse event was
      encountered. CONCLUSIONS: VO can be presented as a safe, well-tolerated, and
      effective herbal preparation in patients with chronic insomnia.

PMID- 25763240
TI  - Factors affecting the prevalence of obesity among primary school students in
      Turkey.
AB  - BACKGROUND: Obesity is an energy metabolism disorder which results in the
      excessive storage of fat and may also lead to physical and psychological
      problems. Since the 1980s, obesity has drastically increased across all age and
      socio-economic groups around the world. OBJECTIVES: The purpose of the study was
      to investigate the risk factors affecting obesity in students in the age group of
      6-15 years. PATIENTS AND METHODS: This was a population-based cross-sectional
      study on 868 students in Bahcelievler elementary school in Zonguldak, Turkey from
      March to April in 2010. Data was collected using demographic questionary forms
      and weight-length measurements. RESULTS: The median age was 10.3 +/- 2.1; 47.6%
      of the children were female and 52.4% of them were male. About 70.2% of the
      students consumed fast food. It was identified that 67.1% of the students in the
      6-10-year age group and 32.9% in 11-15-year age group were obese (P = 0.000). The
      obesity prevalence of children with one or two siblings was higher than the ones
      with more than two siblings (P = 0.001). CONCLUSIONS: The study concluded that
      there were certain criteria related to development of obesity during a specific
      period of childhood and taking certain precautions could be effective in
      preventing it.

PMID- 25763241
TI  - Coenzyme q10 administration in community-acquired pneumonia in the elderly.
AB  - BACKGROUND: Community-acquired pneumonia (CAP) is generally considered a major
      cause of morbidity and mortality in the elderly. OBJECTIVES: This study aimed to
      assess the efficacy of adjunctive coenzyme Q10 (CoQ10) in the treatment of
      elderly CAP. PATIENTS AND METHODS: Hospitalized elderly patients with CAP
      (diagnosed by using defined clinical and radiological criteria) were randomized
      to receive oral CoQ10 (200 mg/d) or placebo for 14 days, along with antibiotics.
      Primary and secondary outcomes on days 3, 7, and 14 were measured. Disease
      severity was scored using CURB-65 index. Statistical analysis was performed using
      SPSS and P value < 0.05 was considered significant. RESULTS: We enrolled 150
      patients for this research. Then, 141 patients, including 70 patients in the
      trial group and 71 patients in the control group were analyzed. Mean age of the
      trial and control groups were 67.6 +/- 7.2 years and 68.7 +/- 7.9 years,
      respectively. Clinical cure at days 3 and 7 were 24 (34.3%) and 62 (88.6%) in the
      trial group (P value = 0.6745) and 22 (31%) and 52 (73.2%) in the placebo group
      (P value = 0.0209). Patients on CoQ10 had faster defervescence (P value = 0.0206)
      and shorter hospital stay (P value = 0.0144) compared with the placebo group. The
      subgroup analysis of the patients with severe pneumonia showed differences in
      clinical cure at day 14. Treatment failure was less in CoQ10 group than in the
      placebo group (10% versus 22.5% and P value = 0.0440). Adverse events in two
      groups were few and similar. CONCLUSIONS: CoQ10 administration has no serious
      side effects and can improve outcome in hospitalized elderly CAP; therefore, we
      recommend it as an adjunctive treatment in elderly patients.

PMID- 25763242
TI  - New therapy using omega-3-Acid ethyl esters for decubitus ulcers and stasis
      dermatitis: a case report.
AB  - INTRODUCTION: In daily practice, it is common to experience difficulty in
      treating decubitus ulcers (pressure ulcers, also known as decubitus ulcers) and
      stasis dermatitis of the lower limbs. We hereby report that omega-3-acid ethyl
      esters were remarkably effective when administered to cases of refractory
      pressure ulcers and stasis dermatitis for the purpose of improving the blood flow
      and promoting blood circulation. CASE PRESENTATION: Case 1: A 21-year-old
      Japanese female with lower-body paralysis. Pressure ulcers appeared on the heel
      and first toe of her left lower extremity. Although the patient had been treated
      with various ointments such as dimethyl isopropylazulene and 0.9% iodine
      containing ointment, the course showed no improvement, so omega-3-acid ethyl
      esters was administered orally, completely healing the ulcer of the first toe in
      10 weeks. Case 2: A 76-year-old Japanese male. The patient had been treated on an
      outpatient basis for 15 years due to hypertension, heart failure, type 2 diabetes
      mellitus, and hyperlipidemia. Two years prior to this presentation, stasis
      dermatitis occurred in the lower limbs and at the end of last year, erosive
      ulcers appeared on the front part of the lower-right thigh and shin. Although
      treatment with various topical ointment and dressings was performed, the course
      showed no improvement. Oral administration of omega-3-acid ethyl esters was
      initiated. At 12 weeks, his condition entered the white phase and healed almost
      completely. CONCLUSIONS: This report is the first to document other treatment
      possibilities for pressure ulcer and/or stasis dermatitis in cases where the use
      of topical applied ointments and medications is difficult. This new therapy may
      therefore help physicians to treat pressure ulcers and stasis dermatitis.

PMID- 25763243
TI  - Association between upstream purine complexes of human caveolin-1 gene and
      schizophrenia in qazvin province of iran.
AB  - BACKGROUND: Caveolin is a multifunctional and scaffolding membrane protein, which
      involves cholesterol trafficking to plasma lipid microdomain. It organizes and
      targets synaptic parts of the neurotransmitter and neurotrophic receptor
      signaling pathways. Caveolins are encoded by CAV-1, 2 and 3 genes. Disruption of
      the CAV1 would likely ruin the neuronal signaling, which leads to symptoms of
      schizophrenia in predisposed individuals. OBJECTIVES: The upper area of CAV-1
      gene is highly conserved and can have a regulatory role in neurodegenerative
      diseases. This study was designed to find out the possible association of
      polymorphisms of this area and schizophrenia. PATIENTS AND METHODS: In a case
      control study, 254 blood samples were obtained from 127 patients with
      schizophrenia and 127 well matched controls referred to 22 Bahman Hospital of
      Qazvin University of Medical Sciences (QUMS) in Qazvin province, Iran, using
      simple random sampling method. After extracting DNA, the upper region of the
      human CAV1- gene was amplified by PCR in all collected samples. The products were
      visualized by silver staining in 10% polyacrylamide gel and then sequenced.
      RESULTS: We detected nine homozygotes in patients and 15 in control subjects.
      Homozygosity was 7.08% and 11.8% in cases and control, respectively. Nine types
      homozygote haplotype were detected in upper region of the CAV1 gene in cases and
      controls. Three haplotypes were common in cases and controls; four haplotypes
      were seen in controls only and two in cases. CONCLUSIONS: Our findings implied a
      significant correlation between some haplotypes of upper region of CAV1 gene and
      schizophrenia. Existence of some haplotypes and lack of another in CAV1 upstream
      can suggest a significant correlation between schizophrenia and some haplotypes.

PMID- 25763244
TI  - Longstanding hypoparathyroidism in a fifty-two-year-old woman misdiagnosed as
      spondyloarthropathy.
AB  - INTRODUCTION: Hypoparathyroidism might cause various musculoskeletal findings,
      resembling Spondyloarthropathies. CASE PRESENTATION: We described a 52-year-old
      woman, diagnosed as a case of undifferentiated spondyloarthropathy for ten years,
      who was unresponsive to classic anti-inflammatory therapies. She developed
      anterior ischemic optic neuropathy and had elevated muscle enzymes during the
      course of disease. On a routine checkup, marked hypocalcemia and suppressed
      parathyroid hormone levels were found. Calcium and calcitriol therapy led to
      clinical and laboratory improvement. CONCLUSIONS: This case emphasizes the
      importance of recognizing rheumatic manifestations of hypoparathyroidism to
      preclude unnecessary treatments. Serum calcium should be included in the
      diagnostic workup of these patients.

PMID- 25763245
TI  - Comparison of bypassing agents in bleeding reduction in treatment of bleeding
      episodes in patients with haemophilia and inhibitors.
AB  - CONTEXT: Mild-to-moderate bleeding disorders in haemophilia are primarily treated
      via recombinant activated factor VII a (rFVIIa) or activated prothrombin complex
      concentrate (aPCC). However, the efficacy of each bypassing agents may vary and
      none of them is universally effective. EVIDENCE ACQUISITION: After reviewing the
      databases of PubMed, Scopus, MD Consult, Ovid, Trip database, Google Scholar,
      ProQuest and the Cochrane Library, finally, 17 papers published from 2000 to 2013
      were extracted. We used as a random effect model in meta-analysis. Comprehensive
      meta-analysis (CMA) software was used for calculating and estimating the mean of
      bleeding reduction and performing meta-analysis. RESULTS: The mean of bleeding
      reduction in aPCC and rFVIIa were 71.2% with CI 95% (lower limit 86.8% and upper
      limit 82%) and 72.3% with CI 95% (lower limit 57.6% and upper limit 83.4%),
      respectively. CONCLUSIONS: Although differences between the two products were
      very close to each other, they reported similar effects on joint bleeds. Further
      clinical studies should be performed by incorporating a standardized measurement
      in comparative efficacy of aPCC and rFVIIa.

PMID- 25763246
TI  - Diagnostic efficacy of vessel specific coronary calcium score in detection of
      coronary artery stenosis.
AB  - BACKGROUND: Coronary artery calcification which is determined quantitatively by
      coronary calcium scoring has been known as a sign of coronary stenosis and thus
      future cardiac events; hence it has been noticed on spotlight of researchers in
      recent years. Developing different method for early and optimal detection of
      coronary artery disease (CAD) is really essential as CAD are the first cause of
      death in population. OBJECTIVES: To evaluate predictive value of vessel specific
      coronary artery calcium (CAC) score in predicting obstructive coronary artery
      disease. PATIENTS AND METHODS: In this diagnostic test study we evaluated
      patients with coronary computed tomography angiography (CCTA) and CAC score which
      had been referred to two referral radiology center in Tehran, Iran and finally we
      selected 2525 patients in a single and sequential pattern to create a diagnostic
      study. The whole-heart CAC scores and vessel specific CAC scores were calculated
      individually for the 4 major epicardial coronary arteries in 2 distinct group;
      group A ( patients with previous history of CABG) and group B (patients without
      history of CABG). For evaluation of obstruction tree cut off points were
      described: 0 > ; at least 1 segment with any kind of stenosis, >= 50; at least 1
      segment with stenosis >= 50, >= 70; at least 1 segment with stenosis >= 70.
      RESULTS: Mean of coronary calcium scores in terms of each coronary artery vessel
      increase by increasing coronary stenosis grade in group B; LAD, RCA, LCX
      respectively have mean CAC score 6.06, 6.21 and 5.04 in normal patients and
      221.6, 226.7 and 106.6 in patients with complete stenosis. As expected these
      findings don't work for group A. Also By increasing calcium score cutoff in all
      four vessels sensitivity decreased and specificity increased but steal LAD had
      higher sensitivity than other vessels and LM had higher specificity. Thus using
      calcium score method is useful for ruling out stenosis in LAD while calcium score
      of LM can predict existence of stenosis in LM. However none of the vessel
      specific CAC can reach to 100% sensitivity and specificity of CCTA method.
      CONCLUSIONS: CCTA is highly superior than vessel specific CAC score thus to
      minimize patients radiation does maybe we can eliminate CAC scan as a routinely
      perform procedure at the beginning of the CCTA.

PMID- 25763247
TI  - Gadolinium Enhanced MR-angiography Results in Patients With Peripheral Arterial
      Disease: Positive Predictive Value Compared to Surgery.
AB  - BACKGROUND: Peripheral arterial disease (PAD) represents systematic
      atherosclerosis of great vessels. PAD affects approximately 10-20 % of patients
      older than 60 years and is associated with high mortality and morbidity rate
      debilitating individuals' life. OBJECTIVES: To compare the results of Gadolinium
      enhanced MR-Angiography and surgery in patients suspected to have peripheral
      arterial disease. MATERIALS AND METHODS: In this prospective cohort study, 30
      consecutive patients matching the inclusion criteria were enrolled and MR
      Angiography was performed prior to surgery for each one. RESULTS: 22 patients
      were male (73.3%) and the mean age was 60.3 +/- 10.6 years in our study group.
      The most common artery for cut off and run off was superior femoral artery in
      both assessments. Proximal section of each artery was the most common anatomical
      section for cut off and run off. There was a same report of cut off artery by MR
      Angiography and surgery (kappa coefficient of agreement was 0.96, P value <
      0.001) and positive predictive value was 0.97 (95% CI: 0.83-0.99). CONCLUSIONS:
      According to our findings MR-angiography is an appropriate alternative imaging
      modality for patients suspected to have peripheral arterial disease and it
      facilitates the early diagnosis proposed by the clinical findings. Also
      beneficial characteristics of this method such as low exposure to ionizing
      radiation, repeatability, and low risk of contrast agent-induced nephropathy make
      it a modality of choice in patients with renal impairment.

PMID- 25763248
TI  - Association of Different MRI BIRADS Descriptors With Malignancy in Non Mass-Like
      Breast Lesions.
AB  - BACKGROUND: Several studies on the diagnostic efficacy of MRI has not real
      consensus for the accuracy of MRI characteristics in non mass like breast
      lesions, and the number of malignant lesions in different studies is
      insufficient. OBJECTIVES: In this study we aimed to analyze the diagnostic role
      of MRI BIRADS features for diagnosis of malignancy in non mass like breast
      lesions. PATIENTS AND METHODS: All patients with positive findings (BIRADS 3, 4,
      5), which had either biopsy proved pathology or follow-up MRI data at least for
      12 months were included in the study. Finally, 213 breasts MRI that showed non
      mass like enhancing lesions among our patients were assessed in study. One
      experienced breast radiologist who was unaware of any clinical information or the
      histopathologic diagnosis evaluated all images retrospectively. The morphologic
      parameters evaluated consisted of distribution modifiers and pattern of internal
      enhancement. The kinetic enhancement parameters were assessed as showing washout,
      plateau, or persistent patterns. In the enhancement kinetic analysis, thew most
      worrisome curve type in each lesion was considered for interpretation, if it was
      more than 2% enhancement. We have evaluated the visual findings by comparison of
      the signal intensity on the first and third dynamic series. Data for the study
      were extracted from the breast MRI database and analyzed using SPSS version 16
      statistical software. RESULTS: Totally 188 patients had 213 non mass like
      lesions. Mean age of the patients was 44.9 +/- 8.3 years (24-63). Totally 46 of
      lesions were malignant (21.6%). The most common BIRADS score was 4 (116; 54.5%).
      The most prevalent feature of distribution, internal enhancement and curve type
      were focal (59.2%), clumped (27.2%) and washout (34.3%). Distribution of
      different subgroups of MR BIRADS features was different among benign and
      malignant lesions (All Pvalues < 0.05). Regarding association with malignancy,
      odds ratio of lesions with segmental or ductal linear distribution was 3.4 (95%
      CI = 1.7-6.8), Clumped, Reticular and Dendritic internal enhancement was 2.5 (95%
      CI = 1.3-5) and wash out curve type was 5.4 (95% CI = 2.7-10.9). Sensitivity of
      higher MR BIRADS (4,5) for diagnosis of malignancy was 100%. Specificity of
      segmental or ductal linear distribution in diagnosis of malignancy was 81%.
      Specificity of BIRADS 5 for diagnosis of malignancy was 98%. In a multivariate
      logistic regression analysis for diagnosis of malignancy in which distribution,
      internal enhancement and curve type were considered as independent variables,
      distribution and curve type remained significant in the model while the internal
      enhancement showed a borderline P-value. CONCLUSIONS: Although in our study
      washout pattern was the most powerful indicator for malignant pathology in non
      mass like enhancing lesions, more studies with larger sample size needs in this
      regard.

PMID- 25763249
TI  - The association between hyperlipidemia and periodontal infection.
AB  - BACKGROUND: Periodontitis is a local chronic inflammatory condition of the
      supporting structures of the teeth resulting from a dental plaque biofilm
      attached to teeth surfaces. Recent studies have indicated that this oral disease
      may have effects on systemic health. OBJECTIVES: The aim of the present study was
      to evaluate the association between periodontitis and hyperlipidemia. PATIENTS
      AND METHODS: This case-control study was conducted in Iran during March 2011. In
      this case-control study, levels of serum lipids in 45 subjects with periodontitis
      were measured and compared with 45 age, gender and body mass index (BMI) matched
      controls. Data were analyzed using student t-test and chi-square test with P <
      0.05 as the limit of significance. RESULTS: Mean values of total cholesterol
      (CHL) (periodontitis group = 218.11 +/- 29.77, control group = 162.31 +/- 48.24)
      and triglycerides (TG) (periodontitis group = 209.77 +/- 44.30, control group =
      125.60 +/- 44.16) were significantly higher in the periodontitis group (P <
      0.001). High-density lipoprotein (HDL) and low-density lipoprotein (LDL)
      cholesterol levels were higher in the case group, but this difference was not
      statistically significant. Frequency of pathological values of CHL and TG were
      significantly higher in cases compared with the controls (P = 0.002 and P =
      0.015, respectively). CONCLUSIONS: This study indicates that hyperlipidemia may
      be associated with periodontal disease in healthy individuals; yet whether
      periodontitis causes an increase in levels of plasma lipids or whether
      hyperlipidemia is a risk factor for periodontal infection and cardiovascular
      disease, it needs further investigations.

PMID- 25763250
TI  - Ramadan fast in patients with coronary artery disease.
AB  - BACKGROUND: Fasting during the month of Ramadan is of vital significance amongst
      Muslims; however, little is known about the effects of this kind of fasting on
      patients with coronary artery disease (CAD). OBJECTIVES: This nonrandomized
      prospective observational pilot study was designed to investigate the effects of
      Ramadan fast on the symptoms of CAD. PATIENTS AND METHODS: Patients with
      documented CAD were consecutively (nonrandomized) included in the study, and
      those with heart failure (ejection fraction < 50%), renal failure, gout, and
      insulin-treated diabetes were excluded. Patients had the choice of fasting during
      Ramadan if they so wished and to break their fast as soon as symptoms such as
      dyspnea and chest pain occurred (fasting group) or not fasting (control group).
      RESULTS: A total of 148 patients completed the study. Mean (mean +/- SD) age of
      the patients was 61.5 +/- 11.7 years and 50% were male. Finally, 66 patients
      (44.6%) accomplished Ramadan fast with an average of 22.27 +/- 10.46 days of
      fasting. Occurrence of chest pain was not significantly different between the
      fasting and non-fasting groups (4 out of 66 [6.1%] vs. 8 out of 82 [9.8%]
      respectively; P = 0.42). In addition, patients who fasted during Ramadan did not
      experience a higher frequency of a combined endpoint of chest pain and dyspnea (4
      out of 66 cases in the fasting group [6.1%] vs. 11 out of 82 in non-fasting group
      [13.4%]; P = 0.14). CONCLUSIONS: In the present study, the patients with CAD were
      able to observe Ramadan fast safely and their combined endpoint of chest pain and
      dyspnea was not significantly different from that of the non-fasting ones. We
      would suggest that patients with CAD and normal left ventricular function could
      fast during Ramadan.

PMID- 25763251
TI  - Effective intervention of self-care on glycaemia control in patients with type 2
      diabetes.
AB  - BACKGROUND: Diabetes is one of the most common diseases, which requires lifelong
      self-care to improve the quality of life. OBJECTIVES: The current study aimed to
      determine the impact of self-care education programs on reducing HbA1c in
      patients with type 2 diabetes. PATIENTS AND METHODS: The current experimental
      study was conducted on 138 female patients with type 2 diabetes in Zahedan city,
      Iran. The data were collected by a self-administered questionnaire which included
      items on demographics, awareness, beliefs, Self-care behaviors. Before the
      educational intervention, the (HbA1c) test check list was completed for the
      patients in both groups. Then the training was applied for the intervention group
      in five 60-minute educational sessions within one month. Three months following
      the training, the data collection based on the check list was repeated for both
      groups. Data were analyzed using SPSS software. RESULTS: The mean scores of
      awareness, beliefs, Self-care behaviors of the educational group, were 46.6 +/-
      8.57, 46.5 +/- 0.86 and 29.06 +/- 10.02, respectively; and it was found that
      after the education, knowledge, attitude, and self-care scores increased
      significantly (P < 0.001 Before the training, the scores of self-care, beliefs,
      and awareness were less than average in the intervention and control groups. In
      addition, the levels of HbA1c in the patients were higher than the normal levels.
      Following the intervention, the mean of self-care and HbA1c of the intervention
      group significantly reduced as compared with those of the control group (P <
      0.001). CONCLUSIONS: Self-care training instructions led to improve knowledge,
      attitude, and performance of the subjects under study and also the average HbA1c.
      Therefore, the nurses and health care staff should be educated accordingly.

PMID- 25763252
TI  - Malignant priapism due to renal cancer: a case report of first manifestation of
      systemic spread.
AB  - INTRODUCTION: Malignant priapism due to cancers is a rare condition that only 30
      cases of kidney cancers were reported. CASE PRESENTATION: We report on the first
      case of simultaneous penile, renal vein, vena cava, liver and ipslateral adrenal
      gland metastases from primary renal cancer in a 56-year-old man. The only
      complain of the patient was a history of painful priapism for one month.
      Corporoglanular shunt surgery was useless. Postoperative imaging showed extensive
      regional and distal metastases and tumor embolus in vena cava as well as renal
      and hepatic vein. CONCLUSIONS: Review of literature showed priapism being the
      first presentation in 20% to 50% of cases, almost all cases have shown very poor
      prognosis. This case report underscored the importance of investigation of
      primary tumors for patients with malignant priapism.

PMID- 25763253
TI  - The association of sexual intercourse during pregnancy with labor onset.
AB  - BACKGROUND: Pregnancy is one of the most critical periods in women's lives.
      Sexual relationships change in this period. Monitoring of uterine contractions
      has been shown increase in uterine activity after sexual intercourse in pregnant
      women. OBJECTIVES: This study aimed to determine the association of sexual
      intercourse during pregnancy with labor onset. PATIENTS AND METHODS: This cross
      sectional study included 120 pregnant women with signs of labor onset at referral
      hospitals of Kashan University of Medical Sciences between November and March
      2012. Signs of labor onset included labor pain, bloody show, or rupture of
      membrane. Subjects were investigated in two groups regarding history of coitus in
      the last week of pregnancy. A questionnaire containing demographic questions,
      obstetrical history, and sexual activity was completed by trained midwife through
      face-to-face interview. Chi-square test, Fisher's exact test, and t-test were
      used to check the homogeneity of the two groups for basic and confounding
      variables. Independent-samples t-test was used to compare differences between
      groups in terms of mean gestational age. RESULTS: There was no significant
      difference between groups in age (P = 0.434), body mass index (P = 0.705),
      neonatal weight (P = 0.421), maternal education (P = 0.963), occupation (P =
      0.381), and parity (P = 0.925). Gestational age at the time of delivery was
      significantly lower in intercourse group in comparison with control group based
      on last menstrual period (P = 0.012) and ultrasonography (P = 0.002). There was
      no correlation between intercourse and cause of admission (P = 0.720). Type of
      delivery (cesarean section or vaginal delivery) was not affected by intercourse
      (P = 0.820) or contact with semen (P = 0.841). Results showed no significant
      difference in neonatal weight based on presence of sexual intercourse (P = 0.422)
      or contact with semen (P = 0.583) at the last week of pregnancy. CONCLUSIONS:
      Sexual activity in last week of pregnancy might be associated with the onset of
      labor. Therefore, in the absence of complications in term pregnancy, sexual
      activity can be considered as a natural way to prevent post term pregnancy.

PMID- 25763254
TI  - Cigarette smoking behavior and the related factors among the students of mashhad
      university of medical sciences in iran.
AB  - BACKGROUND: Tobacco consumption is the second major cause of death and the fourth
      most common risk factor for diseases, worldwide. Epidemiologic studies have
      traced the use of alcohol, tobacco, and illicit substances among medical students
      and physicians. OBJECTIVES: The current study aimed to investigate the prevalence
      of cigarette smoking and the related factors among the students of medical
      sciences in Mashhad University of Medical Sciences, Mashhad, Iran. PATIENTS AND
      METHODS: This cross-sectional study was conducted on 946 health professional
      students in Mashhad University of Medical Sciences (MUMS, Iran) in autumn 2008. A
      standard self-administered questionnaire consisting of socio-demographic data,
      participant smoking status, family and peer smoking, attitudes and beliefs about
      smoking, awareness of cigarette negative effects and reasons for smoking
      cessation was used in the current study. RESULTS: Among the students, 18.3%
      reported having ever tried or experienced with cigarette smoking. The overall
      prevalence of cigarette smoking was 9.8% with significant differences in
      prevalence rates by gender, 17.6% among males and 4.2% among females. Starting
      and continuing smoking was significantly correlated with the family cigarette
      consumption habits. The most common reason to start smoking was friends (24.9%)
      and the most important reason to continue smoking was personal life distress
      (17.6%). The majority of participants (92.3%) reported that they were aware of
      the hazards of smoking. A significant difference regarding awareness of smoking
      hazards was observed between smokers and non-smokers. The most important
      preventive factor for cigarette smoking was religious beliefs (69.1%).
      CONCLUSIONS: Although the prevalence of regular smokers among health professions
      students of MUMS was lower than general populations, but this level is still
      alarming and points at the rapid growth of cigarette use, especially among female
      students. Medical schools should work harder to tackle this phenomenon and
      address it more efficiently in their curricula.

PMID- 25763255
TI  - Liver function and anemia pathogenesis in Iranian traditional medicine.
AB  - BACKGROUND: Nutritional deficiency, bleeding, and inflammation are three main
      causes of anemia. On the other hand, erythropoietin (EPO) production, iron
      availability, and a healthy bone marrow are essential for erythropoiesis.
      Recently, recombinant human erythropoietin (rhEPO) has been used to treat the
      patients already taking iron supplements. In Iranian traditional medicine
      literature, much has been written about anemia and its treatment. OBJECTIVES:
      This study aimed to review Iranian traditional medicine theories in the treatment
      of anemia. MATERIALS AND METHODS: In the present study, authors have attempted to
      find the etiology and pathogenesis of anemia in Iranian traditional Medicine
      Literature and the views of ancient physicians in this field. RESULTS: Our
      findings proved that Iranian traditional medicine defined anemia as blood humor
      production dysfunction, which is caused by several reasons mainly hepatic
      dysfunction. Thus, liver is supposed to be the most important organ in this
      regard. This will make considering hepatoprotective medicines in anemia even in
      patients with non-hepatic problems. CONCLUSIONS: The article presents the
      relation between anemia and liver dysfunction viewed by Iranian traditional
      medicine as an important finding in designing a treatment plan. Despite the new
      findings on the evaluation of liver function (i.e. laboratory tests), it seems
      that further studies for earlier evaluation of liver function in anemia are
      highly required.

PMID- 25763256
TI  - Endoscopic marsupialisation of the lateral frontal sinus mucocele with orbital
      extension: a case report.
AB  - INTRODUCTION: Frontal sinus mucoceles are the commonest among all paranasal
      mucoceles. With introduction of functional endoscopic sinus surgery, surgeons
      prefer endoscopic management of sinus mucoceles, but lesions that appear in the
      lateral part of the frontal sinus can be difficult to access and often need
      external approaches. CASE PRESENTATION: We described a lateral frontal sinus
      mucocele with intra-orbital extension, which was successfully managed by
      endoscopic sinus surgery. CONCLUSIONS: Endoscopic sinus surgery is the treatment
      of choice in most frontal sinus mucoceles including lateral frontal mucoceles.

PMID- 25763257
TI  - Structural and contextual dimensions of Iranian primary health care system at
      local level.
AB  - BACKGROUND: In recent years, family physician plan was established as the main
      strategy of health system in Iran, while organizational structure of the primary
      health care system has remained the same as thirty years ago. OBJECTIVES: This
      study was performed to illustrate structural and contextual dimensions of
      organizational structure and relationship between them in Iranian primary health
      care system at local level. MATERIALS AND METHODS: A cross-sectional quantitative
      study was conducted from January to June 2013, during which 121 questionnaires
      were distributed among senior and junior managers of city health centers at
      Medical Sciences universities in Iran. Validity of the questionnaire was
      confirmed by experts (CVI = 0.089 and CVR more than 0.85) and Cronbach alpha was
      utilized for reliability (alpha = 0.904). We used multistage sampling method in
      this study and analysis of the data was performed by SPSS software using
      different tests. RESULTS: Local level of primary health care system in Iran had
      mechanical structure, but in contextual dimensions the results showed different
      types. There was a significant relationship between structural and contextual
      dimensions (r = 0.642, P value < 0.001). Goals and culture dimensions had
      strongest effects on structural dimensions. CONCLUSIONS: Because of the changes
      in goals and strategies of Iranian health system in recent years, it is urgently
      recommended to reform the current structure to increase efficiency and
      effectiveness of the system.

PMID- 25763258
TI  - The Effect of Hospital Service Quality on Patient's Trust.
AB  - BACKGROUND: The trust is meant the belief of the patient to the practitioner or
      the hospital based on the concept that the care provider seeks the best for the
      patient and will provide the suitable care and treatment for him/her. One of the
      main determinants of patient's trust is the service quality. OBJECTIVES: This
      study aimed to examine the effect of quality of services provided in private
      hospitals on the patient's trust. PATIENTS AND METHODS: In this descriptive cross
      sectional study, 969 patients were selected using the consecutive method from
      eight private general hospitals of Tehran, Iran, in 2010. Data were collected
      through a questionnaire containing 20 items (14 items for quality, 6 items for
      trust) and its validity and reliability were confirmed. Data were analyzed using
      descriptive statistics and multivariate regression. RESULTS: The mean score of
      patients' perception of trust was 3.80 and 4.01 for service quality.
      Approximately 38% of the variance in patient trust was explained by service
      quality dimensions. Quality of interaction and process (P < 0.001) were the
      strongest factors in predicting patient's trust, but the quality of the
      environment had no significant effect on the patients' degree of trust.
      CONCLUSIONS: The interaction quality and process quality were the key
      determinants of patient's trust in the private hospitals of Tehran. To enhance
      the patients' trust, quality improvement efforts should focus on service delivery
      aspects such as scheduling, timely and accurate doing of the service, and
      strengthening the interpersonal aspects of care and communication skills of
      doctors, nurses and staff.

PMID- 25763259
TI  - Comparison of the Effects of Eicosapentaenoic Acid With Docosahexaenoic Acid on
      the Level of Serum Lipoproteins in Helicobacter pylori: A Randomized Clinical
      Trial.
AB  - BACKGROUND: Helicobacter pylori infection is the most common chronic bacterial
      infection around the world and an important cause of gastrointestinal disorders,
      which might be involved in the pathogenesis of some extragastrointestinal
      disturbances as well as changes in serum lipid profile. Hypolipemic properties of
      omega-3 fatty acids have been studied in several studies. OBJECTIVES: The present
      study aimed to compare the effects of eicosapentaenoic acid (EPA) and
      docosahexaenoic acid (DHA) supplementation on the level of serum lipoproteins in
      H. pylori. PATIENTS AND METHODS: In a randomized, double-blinded, placebo
      controlled clinical trial in Iran, 105 Helicobacter pylori were randomly
      allocated to receive 2 g of daily EPA (35 patients), DHA (35 patients), or medium
      chain triglyceride (MCT) oil as placebo (33 patients) along with conventional
      tetra-drug H. pylori eradication regimen for 12 weeks. RESULTS: From 105 included
      patients, 97 (31 in EPA, 33 in DHA, and 33 in control groups) completed the study
      and were included in final analysis. The levels of total cholesterol (TC), low
      density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol
      (HDL-C) and the ratios of TG/HDL-C, TC/HDL-C, and LDL-C/HDL-C were not
      significantly different among the three groups, while the level of triglyceride
      (TG) was statistically different. DHA (-16.6 +/- 30.34) and control (+ 15.32 +/-
      56.47) groups were statistically different with regard to changes in TG levels (P
      = 0.000). CONCLUSIONS: There was no difference between the effects of 2 g of EPA
      or DHA supplementation for 12 weeks on the levels of total cholesterol, LDL-C,
      HDL-C, TC/HDL-C, TG/HDL-C, and LDL-C/HDL-C; however, it had a desirable effect on
      the level of TG in a way that the effect of DHA was clearer.

PMID- 25763260
TI  - Women's Awareness and Attitude Toward Breast Self-Examination in Dezful City,
      Iran, 2013.
AB  - BACKGROUND: Over one million new cases of breast cancer (BC) are diagnosed each
      year with a mortality rate of more than 600 thousand women per year. Breast self
      examination (BSE) is a patient-centered, inexpensive, and noninvasive diagnostic
      test. We focused on the role of screening in BC in early diagnosis. OBJECTIVES:
      The purpose of this study was to evaluate awareness and attitude of women toward
      BSE in Dezful City, Iran, in 2013. PATIENTS AND METHODS: This descriptive cross
      sectional study included 1020 women over 15 years of age in Dezful City, in 2013.
      Simple random clustering was used to enroll accessible women. We have applied the
      available pieces of software for statistical analysis. RESULTS: The mean age of
      recruited women was 37.1 +/- 1.3 and 23.6% of participants had a history of BC in
      themselves or in their relatives (mother, sister, aunt, and grandmother). In
      addition, 70.1% of participants benefited from early diagnosis of BC, 83.3% of
      participants considered BSE necessary and useful for early diagnosis of BC, and
      51% of them performed BSE. There was a statistically significant correlation
      between being married and doing BSE (P = 0.034) and between women's level of
      education and awareness to perform BSE (P = 0.009). CONCLUSIONS: With regard to
      high prevalence of BC in Iran, this study showed a positive attitude of women in
      Dezful City toward BSE. Health policymakers in Dezful City can establish training
      programs to increase women's awareness of BSE and to instruct them to perform it
      properly.

PMID- 25763261
TI  - Angle Kappa Measurements: Normal Values in Healthy Iranian Population Obtained
      With the Orbscan II.
AB  - BACKGROUND: The angle kappa is important in proper centration of corneal ablation
      in keratorefractive surgery. Orbscan II device is widely used preoperatively in
      photoablation surgeries and can be used to measure the angle kappa. OBJECTIVES:
      This study aimed to determine the mean angle kappa and its intercepts in healthy
      young Iranian adults. PATIENTS AND METHODS: In this cross-sectional study,
      orthotropic patients (age range, 18-35 years) who were referred to the Khatam Eye
      Hospital (Mashhad, Iran) were included. Exclusion criteria were as follows:
      history of any eye deviation or strabismus with or without orthoptic or surgical
      treatment; any intraocular, corneal, or keratorefractive surgery; contact lens
      use; any corneal anomaly; any ophthalmic or systemic drug consumption; and
      hyperopic spherical refraction > + 3.00 diopters (D), spherical refraction > 
      5.00 D, or cylindrical refraction > 2.00 D. All of the parameters were measured
      by the same operator through an Orbscan II device. RESULTS: A total of 977
      healthy participants who aged 18 to 45 years were included consecutively. The
      study population consisted of 614 females and 363 males. The average angle kappa
      was 5.00o +/- 1.36o at 240.21o +/- 97.17o in males and 4.97o +/- 1.30o at 244.22o
      +/- 94.39o in females (P = 0.63). The average horizontal (x-axis) angle kappa was
      -0.02o +/- 0.49o, with a mean of -0.02o +/- 0.50o in males and -0.02o +/- 0.49o
      in females (P = 0.93). The average vertical (y-axis) angle kappa was -0.09o +/-
      0.32o, with a mean of -0.09o +/- 0.33o in males and -0.09o +/- 0.32o in females
      (P = 0.74). CONCLUSIONS: By using the normal angle kappa determined in this
      study, pseudodeviations can be identified more precisely in those who might
      undergo keratorefractive surgery.

PMID- 25763262
TI  - Characteristics of the patients with colorectal cancer: epidemiologic study or
      pathology report-based study.

PMID- 25763263
TI  - Auditory steady-state response thresholds in adults with conductive and mild to
      moderate sensorineural hearing loss.
AB  - BACKGROUND: The Auditory steady state response (ASSR) provides a frequency
      specific and automatic assessment of hearing sensitivity and is used in infants
      and difficult-to-test adults. OBJECTIVES: The aim of this study was to compare
      the ASSR thresholds among various types (normal, conductive, and sensorineural),
      degree (normal, mild, and moderate), and configuration (flat and sloping) of
      hearing sensitivity, and measuring the cutoff point between normal condition and
      hearing loss for different frequencies. PATIENTS AND METHODS: This clinical trial
      was performed in Iran and included patients who were referred from Ear, Nose, and
      Throat Department. A total of 54 adults (27 with sensorineural hearing loss, 17
      with conductive hearing losses, and 10 with normal hearing) were randomly chosen
      to participate in our study. The type and degree of hearing loss were determined
      through testing by otoscopy, tympanometry, acoustic reflex, and pure tone
      audiometry. Then the ASSR was tested at carrier frequencies of 500, 1000, 2000,
      and 4000 Hz. RESULTS: The ASSR accurately estimates the behavioral thresholds as
      well as flat and sloping configurations. There was no correlation between types
      of hearing loss and difference of behavioral and ASSR thresholds (P = 0.69). The
      difference between ASSR and behavioral thresholds decreased as severity of
      hearing loss increased. The 40, 35, 30, and 35 dB could be considered as cutoffs
      between normal hearing and hearing loss for 500, 1000, 2000, and 4000 Hz,
      respectively. CONCLUSIONS: The ASSR can accurately predict the degree and
      configuration of hearing loss and discriminate the normal hearing from mild or
      moderate hearing loss and mild from moderate hearing loss, except for 500 Hz. The
      Air-conducted ASSR could not define the type of hearing loss.

PMID- 25763264
TI  - Treatment of Alzheimer's disease in Iranian traditional medicine.
AB  - BACKGROUND: Alzheimer's disease (AD) is a progressive neurodegenerative disease
      with a high prevalence in recent years. Dramatic growth in AD prevalence has
      increased the importance of more researches on AD treatment. History has shown
      that traditional medicine can be a source of inspiration to find new therapies.
      OBJECTIVES: This study tried to codify the recommendations of Iranian traditional
      medicine (ITM) by studying the main medical manuscripts. The second purpose was
      to compare these findings with new medical information. MATERIALS AND METHODS:
      Cardinal traditional medical and pharmacological texts from 10th to 18th century
      were searched for traditional terms of dementia (Nesyan, Fisad-uz-Zekr,
      Faramooshkari) focused on treatment methods. The findings were classified into
      three groups: lifestyle recommendations, dietary approaches, and drug therapies.
      These findings were compared with new medical findings. RESULTS: ITM has dietary
      recommendations for dementia such as increasing consumption of nuts, poultry and
      eggs, milk, and grape products (like raisin and currant). These compounds are
      full of unsaturated fatty acids, cholesterol, and polyphenolic compounds. New
      findings suggest that these substances can help in prevention and treatment of
      AD. ITM has some lifestyle considerations like increasing physical and mental
      activities, listening to music, attending musical feasts, and smelling specific
      perfumes. New medical findings confirm nearly all of these recommendations. Along
      with the aforementioned items, treatment with natural medicines is in the first
      line of traditional treatment of dementia. New investigations show that many of
      these herbs have antioxidant, anti-inflammatory factors and acetylcholine
      esterase inhibitory effects. A few of them also have N-methyl-D-aspartate (NMDA)
      blocking activity. When these herbs are put together in traditional formulations,
      they can comprehensively fight against the disease. CONCLUSIONS: More
      ethnopharmacological and ethnomedical studies on ITM antidementia therapy can be
      followed by fruitful results.

PMID- 25763265
TI  - Spatial modeling of colonic lesions with geographic information systems.
AB  - BACKGROUND: Geographic information system (GIS) software has been used in health
      care systems to display and analyze spatial pattern of diseases and health
      services. OBJECTIVES: This study was performed to assess spatial patterns of
      colon's pathologic lesions based on the pathologic reports and assess whether it
      is possible to use GIS software in health services. PATIENTS AND METHODS:
      Archives of pathology of Namazi and Faghihi hospitals, two main referral centers
      of south-west of Iran, were obtained and reviewed between January 2009 and
      September 2011 for biopsy reports of patients who underwent colonoscopy. Abnormal
      biopsies were categorized into five different subgroups according to the type of
      pathologic specimens. By GIS, spatial patterns of colon biopsies were plotted in
      different maps and spatial auto-correlation of colon biopsies was calculated
      using the Moran's Index. RESULTS: A total of 4815 biopsies from 2663 different
      patients were reviewed, 53.8% of which were men. Abnormal biopsies were 2781 of
      all specimens (57.8%). Neoplastic lesions, inflammatory bowel diseases and polyps
      were 9.3%, 19.3% and 29.2% of total biopsies, respectively. Pathologic biopsies
      were more common in the distal colon. Maps of all biopsies and maps of specific
      pathologies were manifested in GIS. CONCLUSIONS: Our study showed that left-sided
      lesions are still more common in the Iranian population. On the other hand,
      surveying the right side of colon is as important as the distal part, which
      necessitates total colonoscopy.

PMID- 25763266
TI  - Trial of tramadol plus gabapentin for opioid detoxification.
AB  - BACKGROUND: Substance abuse or drug addiction is one of the most important health
      issues in every society, which can lead to physical and mental problems.
      OBJECTIVES: This study aimed to compare the efficacy of tramadol plus gabapentin
      versus methadone use in the treatment of opiate withdrawal. PATIENTS AND METHODS:
      Consenting male subjects who fulfilled the DSM-4 criteria for opiate dependence
      syndrome (opium, residue, and heroin) were randomly assigned in two groups to
      receive tramadol plus gabapentin or methadone. Assessment tools were Adjective
      Rating Scale for Withdrawal (ARSW), Clinical Opiate Withdrawal Scale (COWS) and
      Visual Analogue craving Scale (VAS). Fifty-nine subjects were enrolled and
      evaluated on days 1, 2, 3, 4, 6, and 8 during their 10 days of admission. Twenty
      nine participants received methadone and the other 30 received tramadol plus
      gabapentin for their treatment. RESULTS: Mean (SD) age of the patients in
      methadone group and tramadol plus gabapentin group were 33.9 (7.1) and 32.4.
      (8.1), respectively (P = 0.462). The overall ARSW (P value = 0.263) and COWS (P =
      0.862) scores between the two groups were comparable. The differences in the VAS
      score for craving between the two groups was marginally significant (P = 0.057).
      The highest VAS score was at the third day of admission in both groups and it was
      generally higher in methadone group. CONCLUSIONS: The severity of withdrawal
      syndrome in two groups was not significantly different. The craving was higher in
      the group receiving methadone from the second day of admission even though the
      usage amount was higher in the tramadol plus gabapentin group. The findings of
      this study suggest that the combination of tramadol plus gabapentin is an
      efficient method for opioid detoxification.

PMID- 25763267
TI  - Nurse managers' work life quality and their participation in knowledge
      management: a correlational study.
AB  - BACKGROUND: The association between quality of work life and participation in
      knowledge management is unknown. OBJECTIVES: This study aimed to discover the
      association between quality of work life of nurse managers and their
      participation in implementing knowledge management. MATERIALS AND METHODS: This
      was a correlational study. All nurse managers (71 people) from 11 hospitals
      affiliated with the Social Security Organization in Tehran, Iran, were included.
      They were asked to rate their participation in knowledge management and their
      quality of work life. Data was gathered by a researcher-made questionnaire (May
      June 2012). The questionnaire was validated by content and construct validity
      approaches. Cronbach's alpha was used to evaluate reliability. Finally, 50
      questionnaires were analyzed. The answers were scored and analyzed using mean of
      scores, T-test, ANOVA (or nonparametric test, if appropriate), Pearson's
      correlation coefficient and linear regression. RESULTS: Nurse managers'
      performance to implement knowledge management strategies was moderate. A
      significant correlation was found between quality of work life of nurse managers
      and their participation in implementing knowledge management strategies (r =
      0.82; P < 0.001). The strongest correlations were found between implementation of
      knowledge management and participation of nurse managers in decision making (r =
      0.82; P < 0.001). CONCLUSIONS: Improvement of nurse managers' work life quality,
      especially in decision-making, may increase their participation in implementing
      knowledge management.

PMID- 25763268
TI  - Tumor necrosis factor-alpha polymorphism and susceptibility to multiple sclerosis
      in the Iranian population.
AB  - BACKGROUND: Multiple sclerosis (MS) is an immune-mediated disease of polygenic
      etiology. Tumor necrosis factor-alpha (TNF-alpha) microsatellite as a
      proinflammatory cytokine is believed to play an important role in the etiology of
      this disease. OBJECTIVES: The aim of this study was to investigate the
      association of TNF-alpha microsatellite sequence variation in patients with MS
      and its risk factor in the southern Iranian population. PATIENTS AND METHODS:
      This polymorphism was investigated in an Iranian population of 163 native
      southern people [81 patients with MS according to the poser criteria and 82
      healthy controls (HC) with the same age, sex, social, ethnical and geographical
      features (Hormozgan and Fars provinces)]. All the controls were nonimmunological,
      neurological patients. All the cases and controls were chosen randomly and
      genotyped for polymorphism of TNF-alpha microsatellite. RESULTS: The frequencies
      of TNF-alpha*11 (0.25, P < 0.005) and TNF-alpha*10 (P < 0.005) alleles increased
      in patients with MS compared with controls, showing a significant difference
      among the studied population. CONCLUSIONS: The current study adds evidence to the
      association of TNF-alpha gene polymorphism and MS in this southern south Iranian
      population which is consistent with the genetic analysis of MS in Europeans
      (GAMES) project reports and these two alleles reported in this study may be one
      of the genetic risk factor for MS. Furthermore, this data can be used to build
      the Iranian gene bank for future studies.

PMID- 25763269
TI  - The relationship between learning style preferences and gender, educational major
      and status in first year medical students: a survey study from iran.
AB  - BACKGROUND: Identifying and employing appropriate learning styles could play an
      important role in selecting teaching styles in order to improve education.
      OBJECTIVES: This study aimed to determine the relationship between learning
      styles preferences and gender, educational major and status in first year
      students at Isfahan University of Medical Sciences. PATIENTS AND METHODS: A cross
      sectional study employing the visual-aural-read/write-kinesthetic (VARK) learning
      style's questionnaire was done on 184 first year students of medicine, pharmacy,
      dentistry, nursing and health services management at Isfahan University of
      Medical Sciences in 2012. The validity of the questionnaire was assessed through
      experts' views and reliability was calculated using Cronbach's alpha coefficients
      (alpha = 0.86). Data were analyzed using the SPSS ver.18 software and x(2) test.
      RESULTS: Out of 184 participants who responded to and returned the questionnaire,
      122 (66.3%) were female; more than two-thirds (68.5%) of the enrolled students
      were at the professional doctorate level (medicine, pharmacy, dentistry) and
      31.5% at the undergraduate level (nursing and health services management). Eighty
      nine (48.4%) students preferred a single-modal learning style. In contrast, the
      remaining 95 students (51.6%) preferred multi-modal learning styles. A
      significant relationship between gender and single modal learning styles (P =
      0.009) and between status and learning styles (P = 0.04) was observed.
      CONCLUSIONS: According to the results, male students preferred to use the
      kinesthetic learning style more than females, while, female students preferred
      the aural learning style. Knowledge about the learning styles of students at
      educational institutes is valuable and helps solve learning problems among
      students, and allows students to become better learners.

PMID- 25763270
TI  - Stenosis level, plaque morphology and intima-media thickness of internal carotid
      artery in chronic stable angina and acute coronary syndrome; a comparative study.
AB  - BACKGROUND: Ischemic heart disease (IHD) is the most common cause of
      cardiovascular diseases and divided into two main categories as acute coronary
      syndrome (ACS) and chronic stable angina (CSA). These two groups have stenosis
      and atherosclerosis in the coronary artery, but are more severe in patients with
      ACS. OBJECTIVES: We aimed to find the association between coroner and internal
      carotid artery, also comparing prospectively stenosis level, plaque morphology
      and intima-media thickness of internal carotid between patients with acute
      coronary syndrome (ACS) and chronic stable angina. PATIENTS AND METHODS: In this
      study, 60 patients were enrolled as ACS group chosen from those admitted in CCU
      or referred to clinic. Forty-five patients of CSA group were chosen from those
      referred to clinic. All 105 patients underwent color Doppler sonography, and
      stenosis, plaque morphology and intima media thickness (IMT) were measured.
      RESULTS: In 60 patients with ACS, 49 (81.7%) had no stenosis in ultrasonography
      and 11 (18.3%) had some degrees of stenosis; also 28 (46.7%) and 16 (26.7%) of
      patients had plaque and IMT, respectively. In the rest 45 patients of CSA group,
      just 4 (8.9%), 17 (37.8%) and 8 (17.8%) patients had stenosis, plaque and IMT,
      respectively. Therefore, there was no statistically significant difference
      between the two groups regarding stenosis (P = 0.171), plaque morphology (P =
      0.362) and IMT (P = 0.283) (Power = 90%). CONCLUSIONS: According to the results,
      there were no significant and meaningful differences comparing ACS and CSA groups
      of patients by ECDS using three indicators of stenosis, plaque morphology and IMT
      as indicators of atherosclerosis. Results also display that patients with ACS had
      more stenosis, more plaque and thicker intima-media, but these differences were
      not statistically significant (P < 0.05).

PMID- 25763271
TI  - The effect of sleep health behavioral education on the depression of pregnant
      women with sleep disorders: a randomized control trial.
AB  - BACKGROUND: About 79% of the pregnant women experience sleep disorders and 70% of
      pregnant women experience some symptoms of the depression. Physiologic, hormonal,
      and physical changes of pregnancy can predispose mothers to depression these
      disorders before, during, and after childbirth and might be aggravated by
      neglecting health behavior. Health behavior education might be useful for the
      management of depression in pregnant women. OBJECTIVES: This study aimed to
      evaluate the effect of sleep health behavioral education on the improvement of
      depression in pregnant women with sleep disorders. PATIENTS AND METHODS: This
      study was a randomized clinical trial, performed on 96 pregnant women with sleep
      disorder diagnosed according to the Pittsburgh Sleep Quality Index. Tools for
      data collection included demographic questionnaire and Beck's Depression
      Inventory (BDI). Easy and accessible sampling was done. Participants were
      randomly (simple) allocated to intervention and control groups. In intervention
      group, sleep health behavior education was presented during a four-hour session
      held in weeks 22, 23, 24, and 25; then the patients were followed up to fill out
      the BDIQ in follow-up session at weeks 29 and 33 of pregnancy. The control group
      received no intervention and only received routine prenatal care. The results
      were assessed by Chi-square tests, independent-samples t-test, and Fischer's
      exact-test by SPSS 16. RESULTS: A statistically significant change was reported
      in the severity of depression in pregnant women with sleep disorders in the
      intervention group in comparison to the control group at weeks 29 (P < 0.000) and
      33 (P < 0.00). CONCLUSIONS: Sleep health behavioral education improves depression
      in pregnant women who are experiencing insomnia. Findings from this study add
      support to the reported effectiveness of sleep health behavioral education in the
      prenatal care and clinical management of insomnia in pregnancy.

PMID- 25763272
TI  - The efficacy of systemic corticosteroids in treatment of respiratory tract
      infections during hajj 2012.
AB  - BACKGROUND: Diagnosis and treatment of respiratory tract infections (RTI) in a
      mass-gathering situation such as hajj is a medical challenge that requires quick
      decision-making and considerable knowledge about its etiology and treatment
      methods. High prevalence of RTI during Hajj and tendency of caravan physicians to
      treat of patients quickly in such situation lead to prescription of parenteral
      steroids. Nonetheless, no study has focused on the short-term and long-term
      effects of systemic steroids in Hajj pilgrims with RTI. OBJECTIVES: This study
      focuses on efficacy of systemic consumption of corticosteroids in alleviating
      symptoms of RTI. PATIENTS AND METHODS: This clinical trial was included 1671
      pilgrims in Hajj 2012 who had symptoms of RTI based on caravan physician's
      findings. The patients were divided to two groups to receive either parenteral
      corticosteroid or other drugs. Patients who received antibiotics for bacterial
      infections were excluded. This survey concentrated on general symptoms of RTI
      during Hajj such as fever, musculoskeletal pain, coryza, sore throat, cough,
      dyspnea, and hoarseness before, 24 hours after, and five days after drug
      consumption. For classification and analysis of data, SPSS 17 was used.
      Descriptive statistical and Chi square test were used to compare variables.
      RESULTS: In comparison to corticosteroid injection, treatment without systemic
      corticosteroids could reduce the fever more significantly within five days (P <
      0.05), while it had no effect after 48 hours (P > 0.05). Although corticosteroids
      alleviated the symptoms during the first 48 hours (P > 0.05), they had no more
      effect after five days of consumption (P > 0.05). Treatment with medications
      other than corticosteroid had less effect on reducing coryza (P > 0.05) while
      corticosteroids had significant alleviating effect on coryza, cough, and
      musculoskeletal pain (P < 0.05). CONCLUSIONS: There is a need to conduct more
      comprehensive studies on effect of combination therapy with corticosteroids and
      antibiotics as well as their short-term and long-term adverse effects on the
      immune system. While injecting corticosteroids is commonly administered in
      patients with RTI, they are not recommended due to the lack of data on their long
      term therapeutic and adverse effects.

PMID- 25763273
TI  - Antifungal Effect of Zataria multiflora Essence on Experimentally Contaminated
      Acryl Resin Plates With Candida albicans.
AB  - BACKGROUND: Adherence and colonization of Candida species particularly C.
      albicans on denture surfaces, forms a microbial biofilm, which may result denture
      stomatitis in complete denture users. OBJECTIVES: The purpose of the present
      study was to evaluate the antifungal effect Zataria multiflora essence in
      removing of Candida albicans biofilms on experimentally contaminated resin acryl
      plates. MATERIALS AND METHODS: In the present experimental study, 160 resin
      acrylic plates (10 * 10 * 1 mm) were contaminated by immersion in 1 * 10(3) C.
      albicans suspension for 24 hours to prepare experimental Candida biofilms. The
      total number of Candida cells, which adhered to 20 randomly selected acryl resin
      plates was determined as the Candia load before cleaning. The remaining 140
      plates were divided to seven groups of 20 and immersed in five concentrations of
      Zataria multiflora essence from 50 to 3.125 mg/mL as test, 100000 IU nystatin as
      the positive and sterile physiologic serum as the negative control. The remaining
      Candida cells on each acryl plate were also enumerated and data were analyzed
      using the SPSS 16 software with Kruskal-Wallis and Wilcoxon tests. RESULTS:
      Zataria essence at concentrations of 50 and 25 mg/mL removed 100% of attached
      Candida cells similar to nystatine (MFC), while weaker Zataria essence solutions
      cleaned 88%, 60.5% and 44.7% of attached Candida cells. Kruskal-wallis test
      showed a statistically significant difference between all test groups (P =
      0.0001). In this study 12.5 mg/mL concentration of Zataria multiflora was
      considered as the minimum inhibitory concentration (MIC90). CONCLUSIONS: Zataria
      essence, at concentrations of 50 and 25 mg/mL, effectively removed Candida cells
      that had adhered to the denture surface, similar to the level of removal observed
      for 100000 IU nystatin.

PMID- 25763274
TI  - Comparison of radiological findings of chest x-ray with echocardiography in
      determination of the heart size.
AB  - BACKGROUND: Heart size is an important and effective parameter in chest X-ray
      (CXR) interpretation. Studies indicate that, especially in middle-aged men,
      increased cardiothoracic ratio (CTR) is associated with ischemic heart disease
      (IHD) and increased rate of morbidity and mortality. The CXR is the most common
      imaging examination of the heart. OBJECTIVES: A good quality posterior-anterior
      (PA) chest radiograph is an important indicator of the cardiac size. Nowadays,
      CXR has given its place to more advanced approaches such as two-dimensional
      echocardiography. However, CXR is still more accessible and feasible for most of
      the physicians. This study was designed to compare the findings of CXR and
      echocardiography in determination of the heart size. PATIENTS AND METHODS: This
      cross-sectional study was carried out from 2006 to 2007. A total of 197 patients
      entered the study. The cases had been undergone PA CXR and 2-D echocardiography
      maximum within two days. RESULTS: Of participants, 24.9% had cardiomegaly
      according to the findings of CXR and 50.8% based on echocardiography. There was a
      statistically significant difference between the mean size of Right Ventricular
      End Diastolic Diameter in the patients with cardiothoracic ratio < 50% and >= 50%
      (P = 0.002) as well as Left Ventricular End Diastolic Diameter (P = 0.023). Also,
      a statistically significant difference was seen between echocardiography and CXR
      findings with regard to determination of the heart size (P = 0.003). Nonetheless,
      it is noteworthy that sensitivity and specificity of CXR findings in the
      diagnosis of cardiomegaly were 34%, and 84.5%, respectively. CONCLUSIONS: CTR is
      the most common method of describing the heart size. Increased CTR in CXR is
      associated with poor prognosis, which is suggestive of importance and necessity
      of early diagnosis. Although CXR may not have the same diagnostic accuracy as
      echocardiography, its easy accessibility and high specificity in diagnosis of
      cardiomegaly is very helpful, which can play an important and a cost-benefit
      role, particularly in screening the enlarged heart size. Moreover, according to
      the statistics released by Medical Council of Iran, most of Iranian physicians
      are general practitioners and a few of them are cardiologist.

PMID- 25763275
TI  - Screening of von Willebrand disease in Iranian women with menorrhagia.
AB  - BACKGROUND: Menorrhagia is a common health problem in women, particularly those
      with bleeding disorders. Little is known about the course of menorrhagia or other
      bleeding symptoms in women with the most common congenital bleeding disorder, von
      Willebrand disease (vWD). OBJECTIVES: The aim of this study was to estimate the
      prevalence of vWD in women with diagnosed menorrhagia. MATERIALS AND METHODS: In
      this cross-sectional study, a total of 460 consecutive patients, presenting
      menorrhagia, were analyzed. The initial screening and confirmation tests for the
      diagnosis of vWD included determination of prothrombin time (PT), partial
      thromboplastin time (PTT), bleeding time (BT), fibrinogen, factor VIII, vWF
      antigen, and vWF activity. A questionnaire was filled for every patient. The data
      were then analyzed using the SPSS software. RESULTS: Mean age of our patients was
      32.5 +/- 10.6 years. The level of von Willebrand factor in 22.5% and von
      Willebrand activity in 19.6% of patients was abnormal. The prevalence of vWD
      among patients with menorrhagia was 24%. CONCLUSIONS: The high prevalence of vWD
      among our patients was the same as other previous reports, suggesting low
      awareness about this disease and under diagnosis of mild cases.

PMID- 25763276
TI  - Evaluation of the effect of shift work on serum cholesterol and triglyceride
      levels.
AB  - BACKGROUND: Working outside daylight hours (7 am to 7 pm) is called shift work.
      Shift work is a common practice in many industries and factories such as steel
      industries, petroleum industries, power plants, and in some services such as
      medicine and nursing and police forces, in which professionals provide services
      during day and night. OBJECTIVES: Considering the contradictory reports of
      different studies, we decided to evaluate the effect of shift work on cholesterol
      and triglyceride (TG) levels through a historical cohort on steel industry
      workers. PATIENTS AND METHODS: This retrospective cohort study was performed on
      all the staff of Isfahan's Mobarakeh Steel Company between years 2002 and 2011.
      There were 5773 participants in this study. Data were collected from the medical
      records of the staff using the census method. For analysis of data, generalized
      estimating equation (GEE) regression was used. RESULTS: The results showed a
      significant difference in cholesterol levels between shift workers and day
      workers on the first observation (P < 0.001), yet no such difference was observed
      for TG (P = 0.853). Moreover, the results showed that the variables of age, work
      experience and BMI were not similar between shift workers and day workers.
      Therefore, to remove the effect of such variables, we used GEE regression.
      Despite the borderline difference of cholesterol between regular shift workers
      and day workers, this correlation was not statistically significant (P = 0.051).
      The results for TG also showed no correlation with shift work. CONCLUSIONS:
      According to the findings of this study, there is no relationship between shift
      work and changes in serum TG and cholesterol. The lack of relationship can be due
      to shift plans for shift workers, nutrition, or the "Healthy Heart project" at
      Isfahan Mobarakeh Steel Company.

PMID- 25763277
TI  - The effects of two bathing methods on the time of separation of umbilical cord in
      term babies in Turkey.
AB  - BACKGROUND: Umbilical cord infection developing subsequent to bacterial
      colonization is one of the outstanding reasons of newborn mortality and morbidity
      in underdeveloped and developing countries. OBJECTIVES: This study aimed to
      evaluate the influence of sponge and tub bathing methods on umbilical cord
      separation time in full term babies in Turkey. PATIENTS AND METHODS: This quasi
      experimental and randomized controlled study was performed on 100 healthy term
      newborn babies and their mothers. One-hundred full-term babies (51 sponge
      bathing, 49 tub bathing) born at a state hospital between 14.03.2013 and
      18.05.2013 with gestational age of 38-42 weeks, weighing 2500 grams and above and
      met the selection criteria were included as the study sample. Two booklets were
      prepared about sponge bathing and tub bathing. Mothers were instructed about
      sponge bathing and tub bathing, umbilical cord care in prenatal and postnatal
      periods. The first postnatal visit was performed at the hospital. Home visits and
      telephone calls were continued until the day of cord separation. Number, percent,
      mean and standard deviation values, qui-square and Mann-Whitney U tests were used
      for data assessment. RESULTS: The time of separation of umbilical cord in babies
      who were given sponge bathing (6.1 +/- 1.4) was shorter compared to those given
      tub bathing (8.3 +/- 2.5) (P < 0.005). CONCLUSIONS: Since wetting of umbilical
      cord during tub bathing delays the separation of umbilical cord, sponge bathing
      is recommended for newborns until the umbilical cord falls off.

PMID- 25763278
TI  - Association of body weight and female sexual dysfunction: a case control study.
AB  - BACKGROUND: Obesity is rapidly increasing worldwide with negative effects on
      women's health, psychosocial factors and quality of life. Female sexual
      dysfunction (FSD) is a major public health problem that is worrying for many
      women physically, emotionally and socially. OBJECTIVES: The purpose of this study
      was to investigate the association of body weight with FSD and sexual
      satisfaction, in Ilam, western Iran, in 2010 to 2011. PATIENTS AND METHODS: This
      was a case-control study on 120 women aged 18-50 years [64 with FSD (case), 64
      without FSD (control)] married, from Ilam-IR, who were interviewed as per the
      Iranian version of Female Sexual Function Index (FSFI). Body mass index (BMI) and
      waist-to-hip ratio (WHR) were recorded by researchers. The subjects were randomly
      selected from primary health centers. RESULTS: FSFI score was significantly lower
      in overweight women (P < 0.05). FSFI strongly correlated with body mass index
      (BMI) (r = -0.68, P < 0.001) and waist-to-hip ratio (r = -0.29, P < 0.05) in
      women with FSD. Of sexual function parameters, there was a strong and inverse
      correlation between BMI and arousal (r = -0.71, P < 0.001), lubrication (r = 
      0.61, P < 0.001), orgasm (r = -0.52, P < 0.001) and satisfaction (r = -0.54, P <
      0.001), while pain (r = -0.12, P > 0.05) and desire (r = -0.17, P > 0.05) did not
      correlate with BMI. There was an association between BMI and extreme satisfaction
      (r = -0.28, P < 0.05). Extreme physical pleasure (r = -0.19, P > 0.05) and
      extreme emotional satisfaction (r = -0.16, P > 0.05) were not correlated with
      BMI. CONCLUSIONS: Overweight and obesity negative affect sexuality in women with
      sexual dysfunction. A systematic evaluation of sexual function to disclose a
      cause and effect relationship between obesity and FSD is suggested.

PMID- 25763279
TI  - The relationship between self-esteem and sexual self-concept in people with
      physical-motor disabilities.
AB  - BACKGROUND: Self-esteem is the value that the individuals give themselves, and
      sexual self-concept is also a part of individuality or sexual-self. Impairment or
      disability exists not only in the physical body of disabled people but also in
      their attitudes. Negative attitudes affect the mental health of disabled people,
      causing them to have lower self-esteem. OBJECTIVES: This study aimed to examine
      the relationship between self-esteem and sexual self-concept in people with
      physical-motor disabilities. PATIENTS AND METHODS: This cross-sectional study was
      conducted on 200 random samples with physical-motor disabilities covered by
      Isfahan Welfare Organization in 2013. Data collection instruments were the
      Persian Eysenck self-esteem questionnaire, and five domains (sexual anxiety,
      sexual self-efficacy, sexual self-esteem, sexual fear and sexual depression) of
      the Persian multidimensional sexual self-concept questionnaire. Because of
      incomplete filling of the questionnaires, the data of 183 people were analyzed by
      the SPSS 16.0 software. Data were analyzed using the t-test, Man-Whitney and
      Kruskal-Wallis tests and Spearman correlation coefficient. RESULTS: The mean age
      was 36.88 +/- 8.94 years for women and 37.80 +/- 10.13 for men. The mean scores
      of self-esteem among women and men were 15.80 +/- 3.08 and 16.2 +/- 2.90,
      respectively and there was no statistically significance difference. Comparison
      of the mean scores of sexual anxiety, sexual self-efficacy, sexual self-esteem,
      sexual fear and sexual depression among men and women showed that women scored
      higher than men in all domains. This difference was statistically significant in
      other domains except the sexual self-esteem (14.92 +/- 3.61 vs. 13.56 +/- 4.52)
      (P < 0.05). The Kruskal-Wallis test showed that except for sexual anxiety and
      sexual self-esteem, there was a statistical difference between other domains of
      people's sexual self-concept and degree of disability (P < 0.05). Moreover,
      Spearman coefficient showed that there was only a correlation between men's
      sexual anxiety, sexual self-esteem and sexual self-efficacy with their self
      esteem. This correlation was positive in sexual anxiety and negative in two other
      domains. CONCLUSIONS: Lack of difference in self-esteem of disabled people in
      different degrees of disability and in both men and women suggests that disabled
      people should not be presumed to have low self-esteem, and their different
      aspects of life should be attended to, just like others. Furthermore, studies
      should be designed and implemented based on psychological, social and
      environmental factors that can help disabled people to promote their positive
      sexual self-concept through marriage, and reduce their negative self-concept.

PMID- 25763280
TI  - Polycystic ovary syndrome: aggressive or protective factor for the retina?
      Evaluation of macular thickness and retinal nerve fiber layers using high
      definition optical coherence tomography.
AB  - Objective. To compare macular thickness (MT) and retinal nerve fiber layers
      (RNFL) between women with polycystic ovary syndrome (PCOS) and healthy women.
      Materials and Methods. The study included 45 women with PCOS and 47 ovulatory
      women undergoing clinical-gynecological and ophthalmic evaluations, including
      measurement of MT, RNFL, and optic disc parameters using optical coherence
      tomography. Results. The superior RNFL around the optic nerve was significantly
      thicker in PCOS than in healthy volunteers (P = 0.036). After stratification
      according to insulin resistance, the temporal inner macula (TIM), the inferior
      inner macula (IIM), the nasal inner macula (NIM), and the nasal outer macula
      (NOM) were significantly thicker in PCOS group than in control group (P < 0.05).
      Both the presence of obesity associated with insulin resistance (P = 0.037) and
      glucose intolerance (P = 0.001) were associated with significant increase in the
      PC1 mean score, relative to MT. A significant increase in the PC2 mean score
      occurred when considering the presence of metabolic syndrome (P < 0.0001). There
      was a significant interaction between obesity and inflammation in a decreasing
      mean PC2 score relative to macular RNFL thickness (P = 0.034). Conclusion.
      Decreased macular RNFL thickness and increased total MT are associated with
      metabolic abnormalities, while increased RNFL thickness around the optic nerve is
      associated with hormonal changes inherent in PCOS. 

PMID- 25763281
TI  - Maternal fructose intake induces insulin resistance and oxidative stress in male,
      but not female, offspring.
AB  - Objective. Fructose intake from added sugars correlates with the epidemic rise in
      metabolic syndrome and cardiovascular diseases. However, consumption of beverages
      containing fructose is allowed during gestation. Recently, we found that an
      intake of fructose (10% wt/vol) throughout gestation produces an impaired fetal
      leptin signalling. Therefore, we have investigated whether maternal fructose
      intake produces subsequent changes in their progeny. Methods. Blood samples from
      fed and 24 h fasted female and male 90-day-old rats born from fructose-fed,
      glucose-fed, or control mothers were used. Results. After fasting, HOMA-IR and
      ISI (estimates of insulin sensitivity) were worse in male descendents from
      fructose-fed mothers in comparison to the other two groups, and these findings
      were also accompanied by a higher leptinemia. Interestingly, plasma AOPP and
      uricemia (oxidative stress markers) were augmented in male rats from fructose-fed
      mothers compared to the animals from control or glucose-fed mothers. In contrast,
      female rats did not show any differences in leptinemia between the three groups.
      Further, insulin sensitivity was significantly improved in fasted female rats
      from carbohydrate-fed mothers. In addition, plasma AOPP levels tended to be
      diminished in female rats from carbohydrate-fed mothers. Conclusion. Maternal
      fructose intake induces insulin resistance, hyperleptinemia, and plasma oxidative
      stress in male, but not female, progeny. 

PMID- 25763282
TI  - Prevalence of Overweight and Obesity among Students in the Kumasi Metropolis.
AB  - The aim was to determine the prevalence of obesity and overweight among students
      in the Kumasi metropolis. In a descriptive cross-sectional study, 500 students
      aged 10 to 20 years were examined from two junior high schools selected by
      multistage sampling technique and three randomly selected senior high schools.
      Height and weight were measured in all participants and the body mass index (BMI)
      of each individual was calculated. Body mass index classes were calculated
      according to the International Obesity Task Force standards. Out of the 500
      students, 290 (58.00%) were males and 210 (42.00%) were females. The prevalence
      of underweight, normal weight, overweight, and obesity was 7.40%, 79.60%, 12.20%,
      and 0.80%, respectively. Overweight was more prevalent among students than
      obesity. There is therefore the need to establish effective public health
      promotion campaigns among students in order to curtail future implications on
      health. 

PMID- 25763283
TI  - Physiological properties of supragranular cortical inhibitory interneurons
      expressing retrograde persistent firing.
AB  - Neurons are polarized functional units. The somatodendritic compartment receives
      and integrates synaptic inputs while the axon relays relevant synaptic
      information in form of action potentials (APs) across long distance. Despite this
      well accepted notion, recent research has shown that, under certain
      circumstances, the axon can also generate APs independent of synaptic inputs at
      axonal sites distal from the soma. These ectopic APs travel both toward synaptic
      terminals and antidromically toward the soma. This unusual form of neuronal
      communication seems to preferentially occur in cortical inhibitory interneurons
      following a period of intense neuronal activity and might have profound
      implications for neuronal information processing. Here we show that trains of
      ectopically generated APs can be induced in a large portion of neocortical layer
      2/3 GABAergic interneurons following a somatic depolarization inducing hundreds
      of APs. Sparsely occurring ectopic spikes were also observed in a large portion
      of layer 1 interneurons even in absence of prior somatic depolarization.
      Remarkably, we found that interneurons which produce ectopic APs display specific
      membrane and morphological properties significantly different from the remaining
      GABAergic cells and may therefore represent a functionally unique interneuronal
      subpopulation. 

PMID- 25763284
TI  - A case of phosphoglyceride crystal deposition disease in the pelvic soft tissues
      recurring after initial surgery.
AB  - Phosphoglyceride crystal deposition disease (PGDD) is a rare disease entity that
      is characterized by phosphoglyceride crystal deposition that stimulates the
      formation of masses in soft tissue scars or bones. We report a case of PGDD in
      the pelvic soft tissues that recurred after initial surgical treatment. A 50-year
      old woman was referred to our hospital for the evaluation of pelvic masses that
      were observed on an abdominal ultrasound. Magnetic resonance imaging (MRI)
      revealed masses in the pelvic region, with the largest being 10 cm in diameter.
      The masses were diagnosed as ovarian malignant tumors, and an exploratory
      laparotomy was performed. Operative findings revealed them to be foreign body
      granulomas, and the patient was diagnosed with PGDD. The patient had a history of
      cesarean delivery at the age of 24 years. PGDD is extremely rare, but it should
      be considered in the differential diagnosis of abdominal masses in patients with
      a history of abdominal surgery. 

PMID- 25763285
TI  - Nonpigmented metastatic melanoma in a two-year-old girl: a serious diagnostic
      dilemma.
AB  - Although rare, malignant melanoma may occur in children. Childhood melanomas
      account for only 0.3-3% of all melanomas. In particular the presence of
      congenital melanocytic nevi is associated with an increased risk of development
      of melanoma. We herein report a case of malignant melanoma that developed on a
      giant congenital melanocytic nevus and made a metastasis to the subcutaneous
      tissue of neck in a two-year-old girl. The patient was hospitalized for
      differential diagnosis and treatment of cervical mass with a suspicion of
      hematological malignancy, because the malignant transformation of congenital
      nevus was not noticed before. In this case, we found out a nonpigmented malignant
      tumor of pleomorphic cells after the microscopic examination of subcutaneous
      lesion. Nonpigmented metastatic melanoma was diagnosed by several
      immunohistochemical and flow cytometric studies. She was offered palliative
      chemotherapy; however, her parents did not accept treatment. The patient died
      within 9 months of diagnosis. We emphasized here that the possibility of
      malignant melanoma in the differential diagnosis of childhood tumors should be
      kept in mind. 

PMID- 25763287
TI  - Giant pilomatrixoma presenting in the posterior thorax, a rare location and the
      largest described.
AB  - Pilomatrixoma is a common benign soft tissue neoplasm arising from hair follicle
      cells, typically not exceeding 3 cm and located mainly within the head and neck
      regions. Lesions greater than 3 cm or those located elsewhere are rare and are
      often not thought of or high on a differential diagnosis. Moreover, the
      radiographic features of pilomatrixoma are very nonspecific making the diagnosis
      even more difficult and rarely described in the radiology literature. We present
      the largest reported case of pilomatrixoma measuring 24 cm arising from the
      posterior thorax. Our hope is to increase awareness of this diagnosis for slow
      growing soft tissue masses not located in the classically described locations of
      head and neck, explore the radiographic features on various imaging modalities,
      and review the current radiology literature. 

PMID- 25763286
TI  - Maxillary sinus inflammatory myofibroblastic tumors: a review and case report.
AB  - An inflammatory myofibroblastic tumor (IMT) is an immunohistochemically diverse
      entity demonstrating neoplastic and nonneoplastic qualities. Although IMTs can
      arise in any area of the body, lesions arising in certain sites, namely, the
      nasal cavity, paranasal sinuses, and pterygopalatine fossa, demonstrate a
      heightened neoplastic and invasive potential. Despite case specific complete
      tumor regression and disease remission in response to pharmacotherapeutics, a
      subset of IMTs remain resistant to all forms of therapy. We present such a case,
      a 34-year-old female patient, with a highly resistant, maxillary sinus IMT. Her
      refractory, ALK-1 negative IMT has not responded well to novel therapies reported
      in current literature. This case suggests the role of zonal expressivity within a
      single lesion as a probable mechanism for its highly resistant nature and should
      promote determination of each IMT's cytogenetic profile to provide more effective
      targeted therapy. Paper includes a literature review of all maxillary sinus IMTs
      from 1985 to 2014 along with their immunohistochemical staining, treatments, and
      outcomes. 

PMID- 25763288
TI  - Hair coil penile tourniquet syndrome in an unusual age.
AB  - Penile tourniquet syndrome (PTS), a rare urologic emergency, may lead to
      undesirable results including necrosis and amputation of penis, if not diagnosed
      and treated appropriately. Sometimes these injuries may be accepted as a forensic
      case. Miscellaneous objects used for strangulation can be metallic or
      nonmetallic. Of all ages, the most vulnerable period is infancy. Telogen
      effluvium is the most common cause of PTS in infants who are 0-6 years old. In
      the literature, telogen effluvium as a reason of PTS was not found except for
      this age group. Therefore, we aimed to present a boy who is 8 years old diagnosed
      as PTS because of his mother's hair coil. 

PMID- 25763289
TI  - Primary carcinoid tumor of the testis.
AB  - Primary carcinoid tumors of the testis are a rare entity comprising less than 1%
      of all testicular neoplasms. Their presence should be considered particularly
      when evaluating a testicular lesion in an older male patient. Immunohistochemical
      studies may aid in diagnosis and radiographic evaluation is important to rule out
      metastatic origin. Primary carcinoid tumors of the testis are associated with an
      excellent prognosis; however, surveillance is important given rare reports of
      delayed metastases. 

PMID- 25763290
TI  - Kennel Disinfectants for Microsporum canis and Trichophyton sp.
AB  - The antifungal efficacy of commonly used kennel disinfectants for large surfaces
      was tested using naturally infective material from untreated animals (M. canis
      and Trichophyton sp.) soaked and macerated but unfiltered leaving visible
      fluorescing hairs and/or scales in the test inoculum to create a robust
      challenge. Disinfectants included sodium hypochlorite (1 : 32 and 1 : 100),
      enilconazole (1 : 100), accelerated hydrogen peroxide (1 : 16), potassium
      peroxymonosulfate (1% and 2%), and calcium hypochlorite "dry bleach."
      Disinfectants were tested at a 1 : 10, 1 : 5, and 1 : 1 dilution of test inoculum
      to disinfectant with a 10 min contact time. Good efficacy was defined as a
      disinfectant resulting in no growth. Control plates grew >300 colonies of each
      pathogen per plate. Enilconazole, sodium hypochlorite (all dilutions),
      accelerated hydrogen peroxide, and 2% potassium peroxymonosulfate (but not 1%)
      inhibited all growth of both pathogens at 1 : 10, 1 : 5, and 1 : 1 dilutions.
      Calcium hypochlorite showed no antifungal efficacy (>300 colonies per plate).
      Enilconazole (1 : 100), sodium hypochlorite (1 : 32 or 1 : 100), accelerated
      hydrogen peroxide (1 : 16), and 2% potassium peroxymonosulfate are recommended
      for decontamination of kennels exposed to dermatophyte pathogens. 

PMID- 25763291
TI  - 20-Year History of Korean Society of Interventional Neuroradiology (KSIN).

PMID- 25763292
TI  - Recommendations for carotid stenting in Korea.
AB  - Carotid artery angioplasty with stenting (CAS) is being performed in many
      hospitals in Korea. Most of the guidelines which are being used are similar, but
      the practical aspects such as techniques are different between hospitals. For
      example, usage of various protective devices, the oral antiplatelet regimen prior
      to procedure and placing of temporary pacemaker to prevent bradycardia are
      different between hospitals. In this article, we summarize and propose the
      guidelines for CAS which is currently being accepted in Korea. These guidelines
      may be helpful in providing protocol to neurointerventionalist who perform CAS
      and to standardize the process including reporting of CAS in the future
      comparative trials in Korea. 

PMID- 25763293
TI  - Endovascular Treatment of Intracranial Vertebral Artery Dissecting Aneurysms:
      Follow up Angiographic and Clinical Results of Endovascular Treatment in Serial
      Cases.
AB  - PURPOSE: To report angiographic and clinical results of endovascular treatment in
      45 intracranial vertebral artery dissecting aneurysms (VADAs). MATERIALS AND
      METHODS: From July 2002 to September 2013, a total of 42 patients with 45 VADAs
      received endovascular treatment. Endovascular treatment consisted of internal
      trapping with detachable coils, stent-assisted coiling, and stenting only.
      Immediate and follow-up angiographic findings and clinical outcome were
      retrospectively reviewed. RESULTS: There were 17 ruptured VADAs and 28 unruptured
      VADAs. Overall, 26 VADAs were treated with internal trapping, 14 with stent
      assisted coil embolization, and 5 with stenting only. Immediate angiographic
      results revealed complete occlusion in 31 cases and incomplete occlusion in 14
      cases. Follow-up imaging studies were available in 31 cases. On follow-up
      imaging, antegrade recanalization occurred in 2 of 16 cases treated with internal
      trapping. Aneurysmal recurrence occurred in one case treated with stent-assisted
      coiling. Procedural complications occurred in 8 patients. In cases of unruptured
      VADA, favorable outcome (mRS 0 and 1) was achieved in 26 cases and poor outcome
      (mRS 2-5) in 2 cases. There was no mortality in patients with unruptured VADAs.
      CONCLUSION: Endovascular treatment of intracranial VADA appears to be safe and
      effective. Follow-up angiographic study is needed because parent artery
      recanalization or aneurysmal recurrence can occur.

PMID- 25763294
TI  - Adjuvant Tirofiban Injection Through Deployed Solitaire Stent As a Rescue
      Technique After failed Mechanical Thrombectomy in Acute Stroke.
AB  - PURPOSE: We present our experiences of intra-arterial tirofiban injection through
      a deployed Solitaire stent as a rescue therapy after failed mechanical
      thrombectomy in patients with acute ischemic stroke. MATERIALS AND METHODS: Data
      on 18 patients treated with adjunctive tirofiban injection through a temporarily
      deployed Solitaire stent after failed mechanical thrombectomy were
      retrospectively reviewed. Solitaire stent was used as a primary thrombectomy
      device in 16 of 18 patients. Two patients received manual aspiration thrombectomy
      initially. If initial mechanical thrombectomy failed, tirofiban was injected
      intra-arterially through the deployed Solitaire stent and then subsequent
      Solitaire thrombectomy was performed. RESULTS: Fourteen patients had occlusions
      in the middle cerebral artery, 2 in the distal internal carotid artery, and 2 in
      the basilar artery. Successful recanalization was achieved in 14 patients (77.7%)
      after intra-arterial injection of tirofiban and subsequent Solitaire
      thrombectomy. Three patients without successful recanalization after rescue
      method received angioplasty with stenting. Overall, successful recanalization
      (TICI grades 2b and 3) was achieved in 17 (94.4%) of 18 patients. Periprocedural
      complications occurred in 5 patients: distal migration of emboli in 5 patients
      and vessel perforation in 1. Three patients died. Good functional outcome (mRS <=
      2) was achieved in 9 patients (50.0%) at 3 months. CONCLUSION: Rescue intra
      arterial injection of tirofiban through a temporarily deployed Solitaire stent
      may facilitate further recanalization in cases of failed mechanical thrombectomy
      in patients with acute ischemic stroke.

PMID- 25763295
TI  - Persistent aneurysm growth following pipeline embolization device assisted
      coiling of a fusiform vertebral artery aneurysm: a word of caution!
AB  - The complex morphology of vertebrobasilar fusiform aneurysms makes them one of
      the most challenging lesions treated by neurointerventionists. Different
      management strategies in the past included parent vessel occlusion with or
      without extra-intracranial bypass surgery and endovascular reconstruction by
      conventional stents. Use of flow diversion has emerged as a promising alternative
      option with various studies documenting its efficacy and safety. However, there
      are various caveats associated with use of flow diversion in patients with
      fusiform vertibrobasilar aneurysms especially in patients presenting with acute
      subarachnoid hemorrhage (SAH). We report a rare case of persistent aneurysmal
      growth after coiling and placement of the Pipeline Embolization Device (PED; ev3,
      Irvine, California, USA) for SAH from a fusiform vertebral artery aneurysm. As
      consequences of aneurysm rupture can be devastating especially in patients with a
      prior SAH, the clinical relevance of recognizing and understanding such patterns
      of failure cannot be overemphasized as highlighted in the present case. 

PMID- 25763296
TI  - Trans-arterial Onyx Embolization of a Functional Thoracic Paraganglioma.
AB  - Paragangliomas are rare tumors of the endocrine system. They are highly vascular
      and in some cases hormonally active, making their management challenging.
      Although there is strong evidence of the safety and effectiveness of preoperative
      embolization in the management of spinal tumors, only five cases have been
      reported in the setting of thoracic paragangliomas. We present the case of a 19
      year-old man with a large, primary, functional, malignant paraganglioma of the
      thoracic spine causing a vertebral fracture and spinal cord compression. To our
      knowledge this is the first report of preoperative trans-arterial balloon
      augmented Onyx embolization of a thoracic paraganglioma. 

PMID- 25763297
TI  - Transient cortical blindness following vertebral angiography: a case report.
AB  - Transient cortical blindness (TCB) is a rare but well-known complication of
      cerebral angiography. Its pathophysiology remains uncertain. We would like to
      report a case of TCB in a patient during a follow up vertebral angiogram for post
      coil embolization of left posterior inferior cerebellar artery aneurysm.
      Patient's vision was resumed spontaneously within 24 hours after angiography,
      with no residual neurological deficit in subsequent clinical follow up. Multi
      modality imaging evaluation including vertebral angiography, brain CT and MRI
      performed on same day are presented. 

PMID- 25763298
TI  - Should Men Take Prenatal Vitamins?

PMID- 25763300
TI  - An atypical lateral hernia and concomitant inguinal and umbilical hernias in a
      patient with polycystic kidney disease and an intracranial aneurysm - a combined
      approach of clinical and radiological investigation, endoscopic hernia repair,
      and anatomical cadaver model documentation and a systematic review of the
      literature.
AB  - Atypical hernias are difficult to diagnose due to their rarity and often
      unspecific symptoms. In the literature there exist hints to peri-inguinal
      hernias, i.e. direct lateral hernia, but most of them are forms of Spigelian
      hernias. Since the majority were described during the first half of the past
      century or even earlier, only very few cases have been documented using modern
      diagnostic techniques. We report a unique case of a 51 year old patient
      presenting with an atypical inguinal hernia with concomitant inguinal and
      umbilical hernias in combination with cystic kidney disease and intracranial
      aneurysm. The atypical position of the hernia was assumed from clinical
      inspection, ultrasound and CT scan and verified during pre-peritoneoscopy. Using
      an anatomical cadaver dissection approach, we followed the unusual position of
      the hernia through the abdominal wall below the aponeurosis of the external
      oblique muscle. After a thorough literature search, we assume that the present
      hernia containing a hernial sac has not been documented before, especially not in
      such a multidisciplinary approach comprising radiological, surgical and
      anatomical localisation and endoscopic treatment in a patient with a clinical
      situation being aggravated by large cystic kidneys leading to dialysis
      dependency. Rare hernias have been described as being often associated with
      concomitant inguinal or other hernias, a predisposition for the male gender and a
      pathogenic mechanism related to other soft tissue defects such as cystic kidney
      disease or cranial aneurysm. Thus, we consider this a unique case that has not
      been documented in this constellation previously, which may increase the
      awareness for these rare hernias. 

PMID- 25763301
TI  - A new attractant for monitoring western flower thrips, Frankliniella occidentalis
      in protected crops.
AB  - Monitoring of pest populations is an essential component of integrated pest
      management. An early warning system helps growers decide when best to take
      control measures, or when to alter them, should a control method prove
      inadequate. Studies have shown that adding chemical attractants to sticky cards
      can increase trap catch of western flower thrips, Frankliniella occidentalis, a
      global pest of agriculture and horticulture, giving more accurate accounts of
      population size and dynamics, thus leading to more efficient monitoring. We
      identify a novel semiochemical to the species, (S)-(-)-verbenone, showing that
      addition of this compound to sticky traps significantly increased F. occidentalis
      catch in two geographically distinct populations, infesting two unrelated crops
      of global economic importance. We validate through field trials that (S)-(-)
      verbenone is highly attractive to F.occidentalis and can be used with blue sticky
      traps to enhance trap catch, leading to better estimations of pest population
      densities. The compound may be used in other control methods against
      F.occidentalis such as lure and kill, mass trapping and push-pull. 

PMID- 25763302
TI  - Phosphate fertilizer is a main source of arsenic in areas affected with chronic
      kidney disease of unknown etiology in Sri Lanka.
AB  - Chronic Kidney Disease of unknown etiology (CKDu) has escalated into an epidemic
      in North Central Province (NCP) and adjacent farming areas in the dry zone of Sri
      Lanka. Studies have shown that this special type of CKD is a toxic nephropathy
      and arsenic may play a causative role along with a number of other heavy metals.
      We investigated the hypothesis that chemical fertilizers and pesticide could be a
      source of arsenic. 226 samples of Fertilizers and 273 samples of pesticides were
      collected and analyzed using atomic absorption spectrometry and inductively
      coupled plasma mass spectrometry for arsenic and other heavy metals in two
      university laboratories. Almost all the agrochemicals available to the farmers in
      the study area are contaminated with arsenic. The highest amount was in triple
      super phosphate (TSP) with a mean value of 31 mg/kg. Also TSP is a rich source of
      other nephrotoxic metals including Cr, Co, Ni, Pb and V. Annually more than 0.1
      million tons of TSP is imported to Sri Lanka containing approximately 2100 kg of
      arsenic. The next highest concentration was seen in the rock phosphate obtained
      from an open pit mine in NCP (8.56 mg/kg). Organic fertilizer contained very low
      amounts of arsenic. Arsenic contamination in pesticides varied from 0.18 mg/kg to
      2.53 mg/kg although arsenic containing pesticides are banned in Sri Lanka.
      Glyphosate the most widely used pesticide in Sri Lanka contains average of 1.9
      mg/kg arsenic. Findings suggest that agrochemicals especially phosphate
      fertilizers are a major source of inorganic arsenic in CKDu endemic areas.
      Organic fertilizer available in Sri Lanka is comparatively very low in arsenic
      and hence the farmers in CKDu endemic areas in Sri Lanka should be encouraged to
      minimize the use of imported chemical fertilizer and use organic fertilizers
      instead. 

PMID- 25763303
TI  - Lactic acid bacteria: promising supplements for enhancing the biological
      activities of kombucha.
AB  - Kombucha is sweetened black tea that is fermented by a symbiosis of bacteria and
      yeast embedded within a cellulose membrane. It is considered a health drink in
      many countries because it is a rich source of vitamins and may have other health
      benefits. It has previously been reported that adding lactic acid bacteria
      (Lactobacillus) strains to kombucha can enhance its biological functions, but in
      that study only lactic acid bacteria isolated from kefir grains were tested.
      There are many other natural sources of lactic acid bacteria. In this study, we
      examined the effects of lactic acid bacteria from various fermented Vietnamese
      food sources (pickled cabbage, kefir and kombucha) on kombucha's three main
      biological functions: glucuronic acid production, antibacterial activity and
      antioxidant ability. Glucuronic acid production was determined by high
      performance liquid chromatography-mass spectrometry, antibacterial activity was
      assessed by the agar-well diffusion method and antioxidant ability was evaluated
      by determining the 2,2-diphenyl-1-picrylhydrazyl radical scavenging capacity.
      Four strains of food-borne pathogenic bacteria were used in our antibacterial
      experiments: Listeria monocytogenes ATCC 19111, Escherichia coli ATCC 8739,
      Salmonella typhimurium ATCC 14028 and Bacillus cereus ATCC 11778. Our findings
      showed that lactic acid bacteria strains isolated from kefir are superior to
      those from other sources for improving glucuronic acid production and enhancing
      the antibacterial and antioxidant activities of kombucha. This study illustrates
      the potential of Lactobacillus casei and Lactobacillus plantarum isolated from
      kefir as biosupplements for enhancing the bioactivities of kombucha. 

PMID- 25763304
TI  - Scientific impact of studies published in temporarily available radiation
      oncology journals: a citation analysis.
AB  - The purpose of this study was to review all articles published in two temporarily
      available radiation oncology journals (Radiation Oncology Investigations, Journal
      of Radiosurgery) in order to evaluate their scientific impact. From several
      potential measures of impact and relevance of research, we selected article
      citation rate because landmark or practice-changing research is likely to be
      cited frequently. The citation database Scopus was used to analyse number of
      citations. During the time period 1996-1999 the journal Radiation Oncology
      Investigations published 205 articles, which achieved a median number of 6
      citations (range 0-116). However, the most frequently cited article in the first
      4 volumes achieved only 23 citations. The Journal of Radiosurgery published only
      31 articles, all in the year 1999, which achieved a median number of 1 citation
      (range 0-11). No prospective randomized studies or phase I-II collaborative group
      trials were published in these journals. Apparently, the Journal of Radiosurgery
      acquired relatively few manuscripts that were interesting and important enough to
      impact clinical practice. Radiation Oncology Investigations' citation pattern was
      better and closer related to that reported in several previous studies focusing
      on the field of radiation oncology. The vast majority of articles published in
      temporarily available radiation oncology journals had limited clinical impact and
      achieved few citations. Highly influential research was unlikely to be submitted
      during the initial phase of establishing new radiation oncology journals. 

PMID- 25763305
TI  - On a heuristic point of view concerning the citation distribution: introducing
      the Wakeby distribution.
AB  - The paper proposes a heuristic approach to modeling the cumulative distribution
      of citations of papers in scientific journals by means of the Wakeby
      distribution. The Markov process of citation leading to the Wakeby distribution
      is analyzed using the terminal time formalism. The Wakeby distribution is derived
      in the paper from the simple and general inhomogeneous Choquet-Deny convolution
      equation for a non-probability measure. We give statistical evidence that the
      Wakeby distribution is a reasonable approximation of the empirical citation
      distributions. AMS Subject Classification: 91D30; 91D99. 

PMID- 25763299
TI  - New frontiers for platelet CD154.
AB  - The role of platelets extends beyond hemostasis. The pivotal role of platelets in
      inflammation has shed new light on the natural history of conditions associated
      with acute or chronic inflammation. Beyond the preservation of vascular
      integrity, platelets are essential to tissue homeostasis and platelet-derived
      products are already used in the clinics. Unanticipated was the role of platelets
      in the adaptative immune response, allowing a renewed conceptual approach of auto
      immune diseases. Platelets are also important players in cancer growth and
      dissemination. Platelets fulfill most of their functions through the expression
      of still incompletely characterized membrane-bound or soluble mediators. Among
      them, CD154 holds a peculiar position, as platelets represent a major source of
      CD154 and as CD154 contributes to most of these new platelet attributes. Here, we
      provide an overview of some of the new frontiers that the study of platelet CD154
      is opening, in inflammation, tissue homeostasis, immune response, hematopoiesis
      and cancer. 

PMID- 25763306
TI  - Does sex influence the incidence or severity of reperfusion-induced cardiac
      arrhythmias?
AB  - Whether sex affects the acute phase of myocardial ischemia in experimental animal
      models is currently being debated. Our purpose was to determine if sex influences
      either the incidence or severity of reperfusion-induced arrhythmias resulting
      from a brief coronary occlusion. Male and female Sprague-Dawley rats were
      assigned to the study. Anesthetized animals were subjected to a 5-minute coronary
      artery occlusion followed by 5 minutes of reperfusion. Mortality differed by sex:
      10/27 (37%) of males died due to VT/VF while only 1/16 females (6%) died due to
      VT/VF (p = 0.033). Quantitative analysis of the electrocardiogram was performed
      on data acquired from 17 male and 15 female survivors. Analysis showed no other
      significant differences in ventricular arrhythmias between the two groups.
      CONCLUSION: Lethal reperfusion-induced arrhythmias led to a higher mortality in
      male rats versus female rats. Among survivors there was no difference in any
      other arrhythmic parameters measured.

PMID- 25763307
TI  - Venlafaxine as single therapy associated with hypertensive encephalopathy.
AB  - INTRODUCTION: Hypertensive encephalopathy with the clinicoradiological entity
      posterior reversible encephalopathy syndrome in the setting of venlafaxine as
      single therapy has not been reported earlier. CASE DESCRIPTION: A 46-year-old man
      developed hypertensive encephalopathy associated with venlafaxine as single
      therapy. Magnetic resonance imaging of the brain, pre and post gadolinium,
      carried out on day 2, displayed an increased T2 signal in the cortex on both the
      T2 and FLAIR images throughout the frontal and temporal lobes and in the
      cerebellum. Venlafaxine therapy was stopped. The patient gradually improved and
      he became seizure free and the blood pressure successively became normal. A
      magnetic resonance imaging after six weeks displayed marked regression of the
      abnormalities. On follow-up after 3 months, his blood pressure had been normal
      and he had not had any symptoms. The prescribed antiepileptic drug was
      discontinued as well as antihypertensive treatment. He had not experienced any
      new symptoms at follow-up after one year. DISCUSSION AND EVALUATION: The patient
      in this report had hypertensive encephalopathy associated with venlafaxine
      therapy. The imaging findings are compatible with hypertensive
      encephalopathy/posterior reversible encephalopathy syndrome. Venlafaxine is a
      drug used very frequently. Venlafaxine may infrequently induce hypertensive
      crisis. CONCLUSION: Hypertensive encephalopathy may rarely occur in the setting
      of venlafaxine as single therapy even in low to moderate doses. Patients on
      venlafaxine should have regular monitoring of blood pressure. Knowledge of the
      side effects is vital. Venlafaxine must be discontinued if significant
      hypertension persists.

PMID- 25763308
TI  - The estimation of the Burr-XII parameters with middle-censored data.
AB  - Middle-censoring is considered as a modern general scheme of censoring. In this
      paper, we study the analysis of middle-censored data with Burr-XII distribution
      which is considered one of the most popular and flexible distributions for
      modeling stochastic events and lifetime for many products. The parameters are
      estimated by the maximum likelihood method and the Bayes estimation under gamma
      prior and by applying the Lindley's approximation. A simulation study is carried
      out to compare the performances of the two estimates. Both estimators behave
      almost similarly and verified the consistency property. A real medical data set
      is considered for illustration. 

PMID- 25763309
TI  - Concomitant sentinel lymph node biopsy leading to abbreviated systematic
      lymphadenectomy in a patient with primary malignant melanoma of the vagina.
AB  - INTRODUCTION: Primary malignant melanoma of the vagina is an extremely rare
      disease affecting 3% of patients with malignant vaginal tumors. It is rare
      compared to primary malignant melanoma of the skin and its prognosis is
      unfavorable even in patients with Stage I disease. Here, we report a case of
      primary malignant melanoma of the vagina and discuss our experience with regard
      to previously published literature. CASE DESCRIPTION: The patient was a 59-year
      old female with 2 prior pregnancies and child births. She was examined by a local
      doctor for swelling of the genitalia, and a 1.8 * 1.0 cm large tumor was detected
      on the left side of the vaginal wall. A biopsy indicated leiomyosarcoma, and she
      was referred to our hospital. The tumor was resected, and histopathology of the
      resected sample confirmed the diagnosis of malignant melanoma based on a positive
      surgical margin. Additional courses of treatment included left inguinal sentinel
      lymph node biopsy using an isotope and extended vaginectomy. Although the
      sentinel node was negative, we performed a modified radical hysterectomy and left
      vaginectomy during the third operation because the surgical margin was positive.
      We could not confirm whether the lesion in the extracted sample was malignant,
      and the final diagnosis was primary malignant melanoma of the vagina T4bN0M0
      Stage IIc (UICC 2009). Postoperative adjuvant therapy consisted of 6 cycles of
      DAV-Feron therapy (dacarbazine, ACNU, vincristine, IFN- beta). After 5 months of
      postoperative adjuvant therapy, a 2 cm single lung metastasis was detected in the
      lower left lung. We performed a laparoscopic lower left lobectomy and are
      planning additional chemotherapy. DISCUSSION AND EVALUATION: Currently, surgical
      resection has the highest probability of improving the prognosis of patients when
      used as initial treatment for Stage I disease. By combining treatment with
      sentinel lymph node biopsy, we were able to accurately determine the stage of
      disease and thus avoid systematic lymph node dissection and further surgical
      treatments. CONCLUSION: Malignant melanoma of the vagina is very rare tumor so it
      is necessary to requires the integration of further cases.

PMID- 25763310
TI  - Dynamic electronic institutions in agent oriented cloud robotic systems.
AB  - The dot-com bubble bursted in the year 2000 followed by a swift movement towards
      resource virtualization and cloud computing business model. Cloud computing
      emerged not as new form of computing or network technology but a mere remoulding
      of existing technologies to suit a new business model. Cloud robotics is
      understood as adaptation of cloud computing ideas for robotic applications.
      Current efforts in cloud robotics stress upon developing robots that utilize
      computing and service infrastructure of the cloud, without debating on the
      underlying business model. HTM5 is an OMG's MDA based Meta-model for agent
      oriented development of cloud robotic systems. The trade-view of HTM5 promotes
      peer-to-peer trade amongst software agents. HTM5 agents represent various cloud
      entities and implement their business logic on cloud interactions. Trade in a
      peer-to-peer cloud robotic system is based on relationships and contracts amongst
      several agent subsets. Electronic Institutions are associations of heterogeneous
      intelligent agents which interact with each other following predefined norms. In
      Dynamic Electronic Institutions, the process of formation, reformation and
      dissolution of institutions is automated leading to run time adaptations in
      groups of agents. DEIs in agent oriented cloud robotic ecosystems bring order and
      group intellect. This article presents DEI implementations through HTM5
      methodology. 

PMID- 25763311
TI  - Erratum to: S-wave attenuation in northeastern Sonora, Mexico, near the faults
      that ruptured during the earthquake of 3 May 1887 Mw 7.5.
AB  - [This corrects the article DOI: 10.1186/2193-1801-3-747.]. 

PMID- 25763312
TI  - Trypanosoma cruzi necrotizing meningoencephalitis in a Venezuelan HIV+-AIDS
      patient: pathological diagnosis confirmed by PCR using formalin-fixed- and
      paraffin-embedded-tissues.
AB  - Coinfections with human immunodeficiency virus (HIV) and infectious agents have
      been recognized since the early 90s. In the central nervous system (CNS) of
      HIV(+) patients, parasitic protozoans like Toxoplasma gondii have been described
      as responsible for the space occupying lesions (SOL) developed. However, the
      involvement of Trypanosoma cruzi is also described but appears to be less
      frequent in acquired immunodeficiency syndrome (AIDS) and transplant recipients,
      associated with necrotizing myocarditis and neurological symptoms related to the
      occurrence of necrotizing pseudotumoral encephalitis (NPE) and
      meningoencephalitis (NME). The present work aims to present a Venezuelan case of
      NME associated with the coinfection of HIV and a T. cruzi-like trypanosomatid as
      well as its evolution and diagnosis by histopathological techniques, electron
      microscopy, and PCR methods using formalin-fixed- (FF-) and paraffin-embedded-
      (PE-) tissues. Postmortem cytological studies of leptomeninges imprints reveal
      the presence of trypomastigotes of Trypanosoma sp. Histopathological and electron
      microscopy studies allowed us to identify an amastigote stage and to reject the
      involvement of other opportunistic microorganisms as the etiological agent of the
      SOL. The definitive confirmation of T. cruzi as the etiological agent was
      achieved by PCR suggesting that the NME by T. cruzi was due to a reactivation of
      Chagas' disease. 

PMID- 25763315
TI  - Prognostic efficacy of nuclear morphometry at invasive front of oral squamous
      cell carcinoma: an image analysis microscopic study.
AB  - BACKGROUND: Oral cancer is revisited on a pathologist perspective with advanced
      imaging technique. OBJECTIVE: The present study assessed the new malignancy
      grading system at tumor proper (TP) and Bryne's grading system at invasive tumor
      front (ITF), morphometric features using software, to clarify their associations
      with prognosis of oral cancers. METHODS: Histologically confirmed oral squamous
      cell carcinoma (OSCC) with 5-year follow-up was assessed morphometrically using
      image analysis at TP and ITF, correlated with the prognosis of patient. RESULTS:
      On comparison of grading systems, a moderate agreement between both (Bryne and
      Anneroth) was seen. Among all histological parameters, we noted inverse
      correlation between degree of mitosis at invasive front and decrease in
      lymphoplasmacytic infiltrate at ITF with increase rate of recurrence and event of
      death. An increase in nuclear area, diameter, and perimeter along with decrease
      circularity in advancing OSCC was seen. Correlation of parameters showed higher
      values for maximum nuclear diameter, perimeter, and circularity at TP and ITF
      with recurrence. CONCLUSION: This study, while limited in sample size, concluded
      that a combined assessment of clinical TNM staging, histopathological grading
      system {excluding the parameter "mitotic activity" (due to its inverse
      relation)}, and nuclear morphometry at the ITF are better prognosticators. This
      combination proved to be an accurate predictive factor in eliciting the varied
      molecular characteristics of tumor heterogeneity.

PMID- 25763314
TI  - Observer performance in the use of digital and optical microscopy for the
      interpretation of tissue-based biomarkers.
AB  - BACKGROUND: We conducted a validation study of digital pathology for the
      quantitative assessment of tissue-based biomarkers with immunohistochemistry.
      OBJECTIVE: To examine observer agreement as a function of viewing modality
      (digital versus optical microscopy), whole slide versus tissue microarray (TMA)
      review, biomarker type (HER2 incorporating membranous staining and Ki-67 with
      nuclear staining), and data type (continuous and categorical). METHODS: Eight
      pathologists reviewed 50 breast cancer whole slides (25 stained with HER2 and 25
      with Ki-67) and 2 TMAs (1 stained with HER2, 1 with Ki-67, each containing 97
      cores), using digital and optical microscopy. RESULTS: Results showed relatively
      high overall interobserver and intermodality agreement, with different patterns
      specific to biomarker type. For HER2, there was better interobserver agreement
      for optical compared to digital microscopy for whole slides as well as better
      interobserver and intermodality agreement for TMAs. For Ki-67, those patterns
      were not observed. CONCLUSIONS: The differences in agreement patterns when
      examining different biomarkers and different scoring methods and reviewing whole
      slides compared to TMA stress the need for validation studies focused on specific
      pathology tasks to eliminate sources of variability that might dilute findings.
      The statistical uncertainty observed in our analyses calls for adequate sampling
      for each individual task rather than pooling cases.

PMID- 25763316
TI  - Types and patterns of colonic polyps encountered at a tertiary care center in a
      developing country in South Asia.
AB  - PURPOSE: To identify the prevalence, types, and patterns of colonic polyps in a
      cohort of patients presenting to a tertiary care referral center in Sri Lanka.
      METHODS: Endoscopy and pathology reports of a single unit from 2006 to 2013 were
      analyzed retrospectively. Spearman's correlation coefficient and chi-square test
      were used to identify correlations. RESULTS: There were a total of 158 patients
      (M : F, 10 : 57) who had polyps encountered on colonoscopy (n = 1408) and
      flexible sigmoidoscopy (n = 2402) with an incidence of 4.1%. Mean age was 56.5
      years (SD 16.4) and the incidence of polyps increased with age. The majority
      (81.6%) had one polyp. A total of 188 polyps were assessed and most were seen in
      the rectum (33.5%) followed by sigmoid colon (22.9%). The commonest histological
      type was tubulovillous adenoma (33.5%) followed by tubular adenoma (24.5%). Most
      polyps were benign (91.5%). There was no statistically significant correlation
      with age or gender with malignancy, site, or histology. DISCUSSION AND
      CONCLUSION: The incidence of colorectal polyps was lower than the values reported
      in the west. More polyps were identified in males. There was no statistically
      significant association between age, gender, or multiplicity and malignant change
      in the polyps.

PMID- 25763320
TI  - Cytologic-radiologic correlation using transthoracic CT-guided FNA for lung and
      mediastinal masses: our experience.
AB  - BACKGROUND AND OBJECTIVES: Thoracic lesions account for various benign and
      malignant conditions. Of these lung carcinoma (mainly primary) is the most common
      carcinoma in the world. The present study was undertaken to know the pathological
      spectrum of thoracic lesions and to correlate cytoradiological findings.
      MATERIALS AND METHODS: The present study was conducted in a tertiary care center
      of North India on 74 patients over an 18-month period. CT guided transthoracic
      FNAC (TTFNA) was carried out, and aspirates were drawn, examined, and compared
      with radiological diagnoses. RESULTS: The diagnostic accuracy for FNA in the
      present study was calculated to be 95.94% (using cytology as the gold standard).
      The predominant lesion was malignancy (85.1%), followed by suspicions of
      malignancy and inflammatory pathology (5.40% each). By cytology, the most common
      malignant lesion was adenocarcinoma (48%) followed by squamous cell carcinoma
      (40%), small cell carcinoma (8%), and undifferentiated carcinoma (4%).
      Cytoradiological correlation was found to be 89.2% in the present study.
      CONCLUSION: Present study thus concludes that TT FNA of thoracic lesions is a
      simple, safe, economically prudent technique associated with low morbidity and
      leading to quick and early diagnosis.

PMID- 25763322
TI  - Expression of EGFR and molecules downstream to PI3K/Akt, Raf-1-MEK-1-MAP
      (Erk1/2), and JAK (STAT3) pathways in invasive lung adenocarcinomas resected at a
      single institution.
AB  - Therapies targeting EGFR are effective in treating tumors that harbor molecular
      alterations; however, there is heterogeneity in long-term response to these
      therapies. We retrospectively analyzed protein expression of EGFR, Stat3, phospho
      Akt, and phospho-Erk1/2 by immunohistochemistry in a series of resected cases
      from a single institution, correlated with clinicopathological variables. There
      were 96 patients, with the majority of cases being of low stage tumors (17 pT1a,
      23 pT1b, 30 pT2a, and 18 pT2b). Histologic subtypes were 45 acinar predominant, 2
      cribriform, 25 solid, 7 papillary, 11 lepidic, and 4 mucinous tumors. The EGFR
      score was higher in tumors with vascular invasion (P = 0.013), in solid and
      cribriform acinar histology, and in high stage tumors (P = 0.006 and P = 0.01).
      EGFR was more likely overexpressed in solid compared to lepidic tumors (P =
      0.02). Acinar tumors had the highest rate of ERK1/2 positivity (19%). There was a
      strong correlation among positivity for ERCC1 and other markers, including STAT3
      (P = 0.003), Akt (P = 0.02), and ERK1/ERK2 (P = 0.0005). Expression of molecules
      downstream to EGFR varied from 12% to 31% of tumors; however, the expression did
      not directly correlate to EGFR expression, which may suggest activation of the
      cascades through different pathways. The correlation of protein expression and
      the new lung adenocarcinoma classification may help in the understanding of
      activated pathways of each tumor type, which may act in the oncogenesis and drug
      resistance of these tumors. 

PMID- 25763326
TI  - Salivary RNA signatures in oral cancer detection.
AB  - Oral squamous cell carcinomas (OSCC) are common malignancies that affect almost a
      million people every year. The key issue in reducing mortality and morbidity
      associated with OSCC is to develop novel strategies to identify OSCC at an early
      stage. One such strategy is the identification of biomarkers. So far, more than
      100 biomarkers are recognized in the detection of oral cancer and they range from
      proteins to nucleic acids (DNAs, RNAs). Detection of ribose nucleic acids in
      saliva is a recent trend in diagnosing oral cancer. Studies have shown
      statistically significant changes in the levels of salivary transcriptomes in
      patients with oral squamous cell carcinomas. These biomarkers have displayed high
      sensitivity and specificity. Also, new point-of-care platforms such as oral fluid
      nanosensor test are now available that will soon emerge as chair-side tools for
      early detection of oral cancer. The aim of this review is to highlight the
      importance of salivary transcriptomes in oral cancer detection. 

PMID- 25763333
TI  - Nonalcoholic fatty liver disease: different classifications concordance and
      relationship between degrees of morphological features and spectrum of the
      disease.
AB  - The morphological features of nonalcoholic fatty liver disease (NAFLD) range from
      steatosis to nonalcoholic steatohepatitis (NASH) and cirrhosis. Liver biopsy
      remains the main tool for NASH diagnosis and many histological systems to
      diagnose and grade NAFLD were proposed. We evaluated the relationship among NAFLD
      activity score (NAS), histological diagnoses (non-NASH, possible NASH, and
      definite NASH), and histological algorithm proposed by Bedossa et al.;
      additionally the degrees of morphological features were semiquantified and
      correlated with non-NASH and NASH. Seventy-one liver biopsies were studied. The
      agreement among the three systems considering NASH and non-NASH was excellent
      (Kappa = 0.96). Among the 22 biopsies with NAS 3-4, 72.7% showed to be NASH
      according to Bedossa's algorithm. The degree of steatosis, ballooning, lobular
      inflammation, and fibrosis stage were correlated with NASH (P < 0.001). Fibrosis
      stage 1 was also found in non-NASH. Over the spectrum of NAFLD, no association
      was observed between intensity of steatosis and fibrosis grade. The degrees of
      lobular inflammation showed association with fibrosis stage (P < 0.0001). In
      conclusion, there is agreement among different NAFLD classifications and NAS > 4
      may be a better cutoff from which to consider NASH diagnosis; besides the highest
      degrees of steatosis, ballooning, inflammation, and fibrosis are associated with
      NASH. 

PMID- 25763334
TI  - Feature selection for the automated detection of metaphase chromosomes:
      performance comparison using a receiver operating characteristic method.
AB  - BACKGROUND: The purpose of this study is to identify a set of features for
      optimizing the performance of metaphase chromosome detection under high
      throughput scanning microscopy. In the development of computer-aided detection
      (CAD) scheme, feature selection is critically important, as it directly
      determines the accuracy of the scheme. Although many features have been examined
      previously, selecting optimal features is often application oriented. METHODS: In
      this experiment, 200 bone marrow cells were first acquired by a high throughput
      scanning microscope. Then 9 different features were applied individually to group
      captured images into the clinically analyzable and unanalyzable classes. The
      performance of these different methods was assessed by a receiving operating
      characteristic (ROC) method. RESULTS: The results show that using the number of
      labeled regions on each acquired image is suitable for the first on-line CAD
      scheme. For the second off-line CAD scheme, it would be suggested to combine four
      feature extraction methods including the number of labeled regions, average
      regions area, average region pixel value, and the standard deviation of either
      region distance or circularity. CONCLUSION: This study demonstrates an effective
      method of feature selection and comparison to facilitate the optimization of the
      CAD schemes for high throughput scanning microscope in the future.

PMID- 25763344
TI  - A comparative and evaluative study of two cytological grading systems in breast
      carcinoma with histological grading: an important prognostic factor.
AB  - OBJECTIVE: Cytonuclear gradings in the breast carcinoma raise the level of FNA
      reportage and improves patient management. Our aim was to evaluate and compare
      two cytological grading methods (Robinson's and Mouriquand's) in breast carcinoma
      and correlate it with Nottingham modification of Scarff-Bloom-Richardson (SBR)
      histological grading. MATERIALS AND METHODS: 30 cytologically proven cases of
      infiltrating ductal carcinoma were graded cytologically and histologically.
      Cytograding was done by Robinson's and Mouriquand's methods (grades I to III)
      followed by comparison of the two methods. Cytogradings were correlated with SBR
      grading method. Sensitivity, specificity, diagnostic accuracy, and concordance
      and discordance rates were evaluated. RESULTS: An overall concordance of 76.66%
      between cytogradings, of 83.33% between Robinson's method and SBR, and of 66.66%
      between Mouriquand's method and SBR was seen. Robinson's method correlated best
      with SBR in all the three nuclear grades. Robinson's method showed a diagnostic
      accuracy of 90% with 91.30% sensitivity while Mouriquand's method had an accuracy
      of 76.66% with 95.65% sensitivity. The specificity by Mouriquand's method was
      quite low (14.28%) as compared to Robinson's method (85.71%). CONCLUSION:
      Comprehensive cytological grading of breast cancer by Robinson's method seems
      better because of more objective set of criteria, easy reproducibility, and
      specificity.

PMID- 25763351
TI  - Computer based correlation of the texture of P63 expressed nuclei with
      histological tumour grade, in laryngeal carcinomas.
AB  - BACKGROUND: P63 immunostaining has been considered as potential prognostic factor
      in laryngeal cancer. Considering that P63 is mainly nuclear stain, a possible
      correlation between the texture of P63-stained nuclei and the tumor's grade could
      be of value to diagnosis, since this may be related to biologic information
      imprinted as texture on P63 expressed nuclei. OBJECTIVE: To investigate the
      association between P63 stained nuclei and histologic grade in laryngeal tumor
      lesions. METHODS: Biopsy specimens from laryngeal tumour lesions of 55 patients
      diagnosed with laryngeal squamous cell carcinomas were immunohistochemically
      (IHC) stained for P63 expression. Four images were digitized from each patient's
      IHC specimens. P63 positively expressed nuclei were identified, the percentage of
      P63 expressed nuclei was computed, and 118 textural, morphological, shape, and
      architectural features were calculated from each one of the 55 laryngeal lesions.
      Data were split into the low grade (21 grade I lesions) and high grade (34 grade
      II and grade III lesions) classes for statistical analysis. RESULTS: With
      advancing grade, P63 expression decreased, P63 stained nuclei appeared of lower
      image intensity, more inhomogeneous, of higher local contrast, contained smaller
      randomly distributed dissimilar structures and had irregular shape. CONCLUSION:
      P63 expressed nuclei contain important information related to histologic grade.

PMID- 25763353
TI  - From the Biology of PP2A to the PADs for Therapy of Hematologic Malignancies.
AB  - Over the past decades, an emerging role of phosphatases in the pathogenesis of
      hematologic malignancies and solid tumors has been established. The tumor
      suppressor protein phosphatase 2A (PP2A) belongs to the serine-threonine
      phosphatases family and accounts for the majority of serine-threonine phosphatase
      activity in eukaryotic cells. Numerous studies have shown that inhibition of PP2A
      expression and/or function may contribute to leukemogenesis in several
      hematological malignancies. Likewise, overexpression or aberrant expression of
      physiologic PP2A inhibitory molecules (e.g., SET and its associated SETBP1 and
      CIP2A) may turn off PP2A function and participate to leukemic progression. The
      discovery of PP2A as tumor suppressor has prompted the evaluation of the safety
      and the efficacy of new compounds, which can restore PP2A activity in leukemic
      cells. Although further studies are needed to better understand how PP2A acts in
      the intricate phosphatases/kinases cancer network, the results reviewed herein
      strongly support the development on new PP2A-activating drugs and the immediate
      introduction of those available into clinical protocols for leukemia patients
      refractory or resistant to current available therapies. 

PMID- 25763355
TI  - Phenotype switching in melanoma: implications for progression and therapy.
AB  - Epithelial-mesenchymal transition (EMT) is a key process associated with the
      progression of epithelial cancers to metastatic disease. In melanoma, a similar
      process of phenotype switching has been reported and EMT-related genes have been
      implicated in promotion to a metastatic state. This review examines recent
      research on the role of signaling pathways and transcription factors regulating
      EMT-like processes in melanoma and their association with response to therapy in
      patients, especially response to BRAF inhibition, which is initially effective
      but limited by development of resistance and subsequent progression. We highlight
      studies implicating specific roles of various receptor tyrosine kinases (RTKs) in
      advancing melanoma progression by conferring a proliferative advantage and
      through promoting invasive phenotypes and metastasis. We also review the current
      knowledge of the mechanisms underlying resistance to BRAF inhibition and the
      potential role of melanoma phenotype switching in this process. In particular, we
      discuss how these important new insights may significantly enhance our ability to
      predict patterns of melanoma progression during treatment, and may facilitate
      rational development of combination therapies in the future. 

PMID- 25763354
TI  - PTEN: Multiple Functions in Human Malignant Tumors.
AB  - PTEN is the most important negative regulator of the PI3K signaling pathway. In
      addition to its canonical, PI3K inhibition-dependent functions, PTEN can also
      function as a tumor suppressor in a PI3K-independent manner. Indeed, the PTEN
      network regulates a broad spectrum of biological functions, modulating the flow
      of information from membrane-bound growth factor receptors to nuclear
      transcription factors, occurring in concert with other tumor suppressors and
      oncogenic signaling pathways. PTEN acts through its lipid and protein phosphatase
      activity and other non-enzymatic mechanisms. Studies conducted over the past 10
      years have expanded our understanding of the biological role of PTEN, showing
      that in addition to its ability to regulate proliferation and cell survival, it
      also plays an intriguing role in regulating genomic stability, cell migration,
      stem cell self-renewal, and tumor microenvironment. Changes in PTEN protein
      levels, location, and enzymatic activity through various molecular mechanisms can
      generate a continuum of functional PTEN levels in inherited syndromes, sporadic
      cancers, and other diseases. PTEN activity can indeed, be modulated by mutations,
      epigenetic silencing, transcriptional repression, aberrant protein localization,
      and post-translational modifications. This review will discuss our current
      understanding of the biological role of PTEN, how PTEN expression and activity
      are regulated, and the consequences of PTEN dysregulation in human malignant
      tumors. 

PMID- 25763357
TI  - Embryonic Chicken Transplantation is a Promising Model for Studying the Invasive
      Behavior of Melanoma Cells.
AB  - Epithelial-to-mesenchymal transition is a hallmark event in the metastatic
      cascade conferring invasive ability to tumor cells. There are ongoing efforts to
      replicate the physiological events occurring during mobilization of tumor cells
      in model systems. However, few systems are able to capture these complex in vivo
      events. The embryonic chicken transplantation model has emerged as a useful
      system to assess melanoma cells including functions that are relevant to the
      metastatic process, namely invasion and plasticity. The chicken embryo represents
      an accessible and economical 3-dimensional in vivo model for investigating
      melanoma cell invasion as it exploits the ancestral relationship between melanoma
      and its precursor neural crest cells. We describe a methodology that enables the
      interrogation of melanoma cell motility within the developing avian embryo. This
      model involves the injection of melanoma cells into the neural tube of chicken
      embryos. Melanoma cells are labeled using fluorescent tracker dye, Vybrant DiO,
      then cultured as hanging drops for 24 h to aggregate the cells. Groups of
      approximately 700 cells are placed into the neural tube of chicken embryos prior
      to the onset of neural crest migration at the hindbrain level (embryonic day 1.5)
      or trunk level (embryonic day 2.5). Chick embryos are reincubated and analyzed
      after 48 h for the location of melanoma cells using fluorescent microscopy on
      whole mounts and cross-sections of the embryos. Using this system, we compared
      the in vivo invasive behavior of epithelial-like and mesenchymal-like melanoma
      cells. We report that the developing embryonic microenvironment confers motile
      abilities to both types of melanoma cells. Hence, the embryonic chicken
      transplantation model has the potential to become a valuable tool for in vivo
      melanoma invasion studies. Importantly, it may provide novel insights into and
      reveal previously unknown mediators of the metastatic steps of invasion and
      dissemination in melanoma. 

PMID- 25763358
TI  - Towards a molecular classification of colorectal cancer.

PMID- 25763356
TI  - OX40 Agonists and Combination Immunotherapy: Putting the Pedal to the Metal.
AB  - Recent studies have highlighted the therapeutic efficacy of immunotherapy, a
      class of cancer treatments that utilize the patient's own immune system to
      destroy cancerous cells. Within a tumor the presence of a family of negative
      regulatory molecules, collectively known as "checkpoint inhibitors," can inhibit
      T cell function to suppress anti-tumor immunity. Checkpoint inhibitors, such as
      CTLA-4 and PD-1, attenuate T cell proliferation and cytokine production. Targeted
      blockade of CTLA-4 or PD-1 with antagonist monoclonal antibodies (mAbs) releases
      the "brakes" on T cells to boost anti-tumor immunity. Generating optimal "killer"
      CD8 T cell responses also requires T cell receptor activation plus co
      stimulation, which can be provided through ligation of tumor necrosis factor
      receptor family members, including OX40 (CD134) and 4-1BB (CD137). OX40 is of
      particular interest as treatment with an activating (agonist) anti-OX40 mAb
      augments T cell differentiation and cytolytic function leading to enhanced anti
      tumor immunity against a variety of tumors. When used as single agents, these
      drugs can induce potent clinical and immunologic responses in patients with
      metastatic disease. However, each of these agents only benefits a subset of
      patients, highlighting the critical need for more effective combinatorial
      therapeutic strategies. In this review, we will discuss our current understanding
      of the cellular and molecular mechanisms by which OX40 agonists synergize with
      checkpoint inhibitor blockade to augment T cell-mediated anti-tumor immunity and
      the potential opportunities for clinical translation of combinatorial
      immunotherapeutic strategies. 

PMID- 25763361
TI  - HIV and bone mineral density.

PMID- 25763359
TI  - Streptococcus mutans-derived extracellular matrix in cariogenic oral biofilms.
AB  - Biofilms are highly structured microbial communities that are enmeshed in a self
      produced extracellular matrix. Within the complex oral microbiome, Streptococcus
      mutans is a major producer of extracellular polymeric substances including
      exopolysaccharides (EPS), eDNA, and lipoteichoic acid (LTA). EPS produced by S.
      mutans-derived exoenzymes promote local accumulation of microbes on the teeth,
      while forming a spatially heterogeneous and diffusion-limiting matrix that
      protects embedded bacteria. The EPS-rich matrix provides mechanical
      stability/cohesiveness and facilitates the creation of highly acidic
      microenvironments, which are critical for the pathogenesis of dental caries. In
      parallel, S. mutans also releases eDNA and LTA, which can contribute with matrix
      development. eDNA enhances EPS (glucan) synthesis locally, increasing the
      adhesion of S. mutans to saliva-coated apatitic surfaces and the assembly of
      highly cohesive biofilms. eDNA and other extracellular substances, acting in
      concert with EPS, may impact the functional properties of the matrix and the
      virulence of cariogenic biofilms. Enhanced understanding about the assembly
      principles of the matrix may lead to efficacious approaches to control biofilm
      related diseases. 

PMID- 25763360
TI  - [Pharmacogenomic Biomarkers for the Prediction of Statin Efficacy and Safety].

PMID- 25763362
TI  - Occurrence of HBV/HIV coinfection by laboratory values in Roma, Lesotho.
AB  - OBJECTIVE: This study was an assessment of the coinfection status of patients
      with human immunodeficiency virus (HIV) and hepatitis B virus (HBV) in Lesotho,
      and this has been rarely reported. METHODS: This was a retrospective study, in a
      laboratory setting, on HBV/HIV coinfection among 304 HIV-positive patients who
      were screened for HBsAg in St Joseph's Hospital records between March 2011 and
      December 2013. Demographic characteristics, HIV status, indications for HBsAg
      screening, HBsAg results and liver function test results including alanine
      transaminase (ALT), aspartate transaminase (AST) and alkaline phosphatase were
      reviewed from the patient and laboratory registers. RESULTS: In this study 10.5%
      of 304 HIV-positive patients had HBV/HIV coinfection. With respect to gender,
      males had a significantly higher (p=0.048) rate of HBV/HIV coinfection in this
      study. Increased levels of ALT (p=0.013) and AST (p=0.014) were significantly
      associated with HBV/HIV coinfection status. CONCLUSION: Gender and liver function
      tests are important predictors for HBV/HIV coinfection. Screening for HBV
      coinfection in HIV-positive patients is recommended.

PMID- 25763363
TI  - Nocardia isolation from clinical samples with the paraffin baiting technique.
AB  - BACKGROUND: The genus Nocardia is a cause of infection in the lungs, skin, brain,
      cerebrospinal fluid, eyes, joints and kidneys. Nocardia isolation from
      polymicrobial specimens is difficult due to its slow growth. Several methods have
      been reported for Nocardia isolation from clinical samples. In the current study,
      we used three methods: paraffin baiting technique, paraffin agar, and
      conventional media for Nocardia isolation from various clinical specimens from
      Iranian patients. METHODS: In this study, we examined 517 samples from various
      clinical specimens such as: sputum of patients with suspected tuberculosis,
      bronchoalveolar lavage, sputum of patients with cystic fibrosis, tracheal
      aspirate, cutaneous and subcutaneous abscesses, cerebrospinal fluid, dental
      abscess, mycetoma, wound, bone marrow biopsy, and gastric lavage. All collected
      specimens were cultured on carbon-free broth tubes (paraffin baiting technique),
      paraffin agar, Sabouraud dextrose agar, and Sabouraud dextrose agar with
      cycloheximide and were incubated at 35 degrees C for one month. RESULTS: Seven
      Nocardia spp. were isolated with paraffin baiting technique, compared with 5
      positive results with the paraffin agar technique and 3 positive results with
      Sabouraud dextrose agar with and without cycloheximide. The prevalence of
      nocardial infections in our specimens was 5.28%. CONCLUSION: In the present
      study, the use of the paraffin baiting technique appeared to be more effective
      than other methods for Nocardia isolation from various clinical specimens.

PMID- 25763366
TI  - Grand challenges in public health policy.

PMID- 25763365
TI  - Unusual cause of chest pain mimicking acute myocardial infarction: congenital
      left ventricular aneurysm.

PMID- 25763364
TI  - Endocrine dysfunction in sepsis: a beneficial or deleterious host response?
AB  - Sepsis is a systemic, deleterious inflammatory host response triggered by an
      infective agent leading to severe sepsis, septic shock and multi-organ failure.
      The host response to infection involves a complex, organized and coherent
      interaction between immune, autonomic, neuroendocrine and behavioral systems.
      Recent data have confirmed that disturbances of the autonomic nervous and
      neuroendocrine systems could contribute to sepsis-induced organ dysfunction.
      Through this review, we aimed to summarize the current knowledge about the
      endocrine dysfunction as response to sepsis, specifically addressed to
      vasopressin, copeptin, cortisol, insulin and leptin. We searched the following
      readily accessible, clinically relevant databases: PubMed, UpToDate, BioMed
      Central. The immune system could be regarded as a "diffuse sensory organ" that
      signals the presence of pathogens to the brain through different pathways, such
      as the vagus nerve, endothelial activation/dysfunction, cytokines and neurotoxic
      mediators and the circumventricular organs, especially the neurohypophysis. The
      hormonal profile changes substantially as a consequence of inflammatory mediators
      and microorganism products leading to inappropriately low levels of vasopressin,
      sick euthyroid syndrome, reduced adrenal responsiveness to ACTH, insulin
      resistance, hyperglycemia as well as hyperleptinemia. In conclusion, clinical
      diagnosis of this "pan-endocrine illness" is frequently challenging due to the
      many limiting factors. The most important benefits of endocrine markers in the
      management of sepsis may be reflected by their potential to be used as biomarkers
      in different scoring systems to estimate the severity of the disease and the risk
      of death. 

PMID- 25763367
TI  - Serbian experience with national health accounts.

PMID- 25763368
TI  - Biomass and neutral lipid production in geothermal microalgal consortia.
AB  - Recently, technologies have been developed that offer the possibility of using
      algal biomass as feedstocks to energy producing systems - in addition to oil
      derived fuels (Bird et al., 2011, 2012). Growing native mixed microalgal
      consortia for biomass in association with geothermal resources has the potential
      to mitigate negative impacts of seasonally low temperatures on biomass production
      systems as well as mitigate some of the challenges associated with growing
      unialgal strains. We assessed community composition, growth rates, biomass, and
      neutral lipid production of microalgal consortia obtained from geothermal hot
      springs in the Great Basin/Nevada area that were cultured under different thermal
      and light conditions. Biomass production rates ranged from 39.0 to 344.1 mg C L(
      1) day(-1). The neutral lipid production in these consortia with and without
      shifts to lower temperatures and additions of bicarbonate (both environmental
      parameters that have been shown to enhance neutral lipid production) ranged from
      0 to 38.74 mg free fatty acids (FFA) and triacylglycerols (TAG) L(-1 )day(-1);
      the upper value was approximately 6% of the biomass produced. The higher lipid
      values were most likely due to the presence of Achnanthidium sp. Palmitic and
      stearic acids were the dominant free fatty acids. The S/U ratio (the saturated to
      unsaturated FA ratio) decreased for cultures shifted from their original
      temperature to 15 degrees C. Biomass production was within the upper limits of
      those reported for individual strains, and production of neutral lipids was
      increased with secondary treatment. All results demonstrate a potential of
      culturing and manipulating resultant microalgal consortia for biomass-based
      energy production and perhaps even for biofuels. 

PMID- 25763371
TI  - Editors' page.

PMID- 25763370
TI  - Targeting Cell Cycle Proteins in Breast Cancer Cells with siRNA by Using Lipid
      Substituted Polyethylenimines.
AB  - The cell cycle proteins are key regulators of cell cycle progression whose
      deregulation is one of the causes of breast cancer. RNA interference (RNAi) is an
      endogenous mechanism to regulate gene expression and it could serve as the basis
      of regulating aberrant proteins including cell cycle proteins. Since the delivery
      of small interfering RNA (siRNA) is a main barrier for implementation of RNAi
      therapy, we explored the potential of a non-viral delivery system, 2.0 kDa
      polyethylenimines substituted with linoleic acid and caprylic acid, for this
      purpose. Using a library of siRNAs against cell cycle proteins, we identified
      cell division cycle protein 20 (CDC20), a recombinase RAD51, and serine-threonine
      protein kinase CHEK1 as effective targets for breast cancer therapy, and
      demonstrated their therapeutic potential in breast cancer MDA-MB-435, MDA-MB-231,
      and MCF7 cells with respect to another well-studied cell cycle protein, kinesin
      spindle protein. We also explored the efficacy of dicer-substrate siRNA (DsiRNA)
      against CDC20, RAD51, and CHEK1, where a particular DsiRNA against CDC20 showed
      an exceptionally high inhibition of cell growth in vitro. There was no apparent
      effect of silencing selected cell cycle proteins on the potency of the
      chemotherapy drug doxorubicin. The efficacy of DsiRNA against CDC20 was
      subsequently assessed in a xenograft model, which indicated a reduced tumor
      growth as a result of CDC20 DsiRNA therapy. The presented study highlighted
      specific cell cycle protein targets critical for breast cancer therapy, and
      provided a polymeric delivery system for their effective down-regulation. 

PMID- 25763372
TI  - PARADIGM-HF: Have we achieved a new paradigm in the treatment of heart failure?

PMID- 25763369
TI  - Analysis of genetic variation and potential applications in genome-scale
      metabolic modeling.
AB  - Genetic variation is the motor of evolution and allows organisms to overcome the
      environmental challenges they encounter. It can be both beneficial and harmful in
      the process of engineering cell factories for the production of proteins and
      chemicals. Throughout the history of biotechnology, there have been efforts to
      exploit genetic variation in our favor to create strains with favorable
      phenotypes. Genetic variation can either be present in natural populations or it
      can be artificially created by mutagenesis and selection or adaptive laboratory
      evolution. On the other hand, unintended genetic variation during a long term
      production process may lead to significant economic losses and it is important to
      understand how to control this type of variation. With the emergence of next
      generation sequencing technologies, genetic variation in microbial strains can
      now be determined on an unprecedented scale and resolution by re-sequencing
      thousands of strains systematically. In this article, we review challenges in the
      integration and analysis of large-scale re-sequencing data, present an extensive
      overview of bioinformatics methods for predicting the effects of genetic variants
      on protein function, and discuss approaches for interfacing existing
      bioinformatics approaches with genome-scale models of cellular processes in order
      to predict effects of sequence variation on cellular phenotypes. 

PMID- 25763373
TI  - NIAMI: Towards the optimization of results in primary PCI.
AB  - The NAIMI trial has recently been published. It assessed one of the most
      contemporary and challenging issues in the management of acute myocardial
      infarction (AMI), namely prevention of reperfusion injury (RPI) after primary PCI
      for ST-elevation myocardial infarction (STEMI). It investigated the effect of the
      intravenous administration of Na nitrite given immediately prior to primary PCI
      for STEMI in 229 patients (118 in the treatment group, and 111 in placebo). The
      myocardial infarction (MI) size did not differ between the two groups as observed
      by cardiac MRI (CMR) with gadolinium enhancement at 6-8 days or plasma Troponin-I
      and creatine kinase (CK), or by left ventricular (LV) volume and ejection
      fraction (EF) as measured by echocardiography at 6-8 days and again at 6 months.
      They concluded that IV nitrites did not reduce the infarct size. There was,
      however, a trend towards benefit in diabetic patients in the post-hoc analysis.
      The small number of these subjects has probably lead to inconclusive outcome in
      this subset. 

PMID- 25763374
TI  - HPS2-THRIVE, AIM-HIGH and dal-OUTCOMES: HDL-cholesterol under attack.

PMID- 25763375
TI  - APOC3: Triglycerides do matter.

PMID- 25763376
TI  - REVERSE 5-year follow up: CRT impact persists.
AB  - The role of cardiac resynchronization therapy (CRT) in patients presenting with
      mild manifestations of heart failure (HF), depressed left ventricular ejection
      fraction (LV EF), and wide QRS complex, has been addressed in four previous
      trials: MIRACLE ICD II,(1) MADIT-CRT,(2) RAFT,(3) and REVERSE.(4) The consistent
      observed benefits in reverse cardiac remodelling and reduction of heart failure
      adverse events have resulted in guideline recommendations for CRT in NYHA Class
      II patients. The guidelines also recommend further studies to determine whether
      survival is increased by CRT in patients with mild symptoms. The 5-year analysis
      of the REsynchronization reVErses Remodeling Systolic left vEntricular (REVERSE)
      trial, which was designed prospectively for 5-year follow-up to specifically
      assess the long term benefits of CRT, were recently published in the European
      Heart Journal.(5). 

PMID- 25763377
TI  - PARIS: A good start for exercise in HFPEF.

PMID- 25763378
TI  - The Dabigatran debate.

PMID- 25763380
TI  - Antegrade flow in Anomalous Left Coronary Artery from Pulmonary Artery: Clinical
      implications.
AB  - Anomalous origin of the left main coronary artery from the pulmonary artery
      (ALCAPA) is a rare congenital anomaly that usually presents in childhood. It
      results in left ventricular (LV) ischemia with resulting LV dysfunction. This
      ischemia results from retrograde flow into the pulmonary artery which can act as
      a coronary steal. We here report antegrade flow detected in ALCAPA caused by
      severe pulmonary hypertension. Anatomic correction of ALCAPA is the preferred
      surgical option and should be performed as early as possible. 

PMID- 25763381
TI  - Quantitative assessment of right ventricular structure and flow dynamics in
      pulmonary homograft obstruction.

PMID- 25763379
TI  - Reprogramming for cardiac regeneration.
AB  - Treatment of cardiovascular diseases remains challenging considering the limited
      regeneration capacity of the heart muscle. Developments of reprogramming
      strategies to create in vitro and in vivo cardiomyocytes have been the focus
      point of a considerable amount of research in the past decades. The choice of
      cells to employ, the state-of-the-art methods for different reprogramming
      strategies, and their promises and future challenges before clinical entry, are
      all discussed here. 

PMID- 25763382
TI  - A classification of basic helix-loop-helix transcription factors of soybean.
AB  - The complete genome sequence of soybean allows an unprecedented opportunity for
      the discovery of the genes controlling important traits. In particular, the
      potential functions of regulatory genes are a priority for analysis. The basic
      helix-loop-helix (bHLH) family of transcription factors is known to be involved
      in controlling a wide range of systems critical for crop adaptation and quality,
      including photosynthesis, light signalling, pigment biosynthesis, and seed pod
      development. Using a hidden Markov model search algorithm, 319 genes with basic
      helix-loop-helix transcription factor domains were identified within the soybean
      genome sequence. These were classified with respect to their predicted DNA
      binding potential, intron/exon structure, and the phylogeny of the bHLH domain.
      Evidence is presented that the vast majority (281) of these 319 soybean bHLH
      genes are expressed at the mRNA level. Of these soybean bHLH genes, 67% were
      found to exist in two or more homeologous copies. This dataset provides a
      framework for future studies on bHLH gene function in soybean. The challenge for
      future research remains to define functions for the bHLH factors encoded in the
      soybean genome, which may allow greater flexibility for genetic selection of
      growth and environmental adaptation in this widely grown crop. 

PMID- 25763384
TI  - Robust vehicle detection under various environments to realize road traffic flow
      surveillance using an infrared thermal camera.
AB  - To realize road traffic flow surveillance under various environments which
      contain poor visibility conditions, we have already proposed two vehicle
      detection methods using thermal images taken with an infrared thermal camera. The
      first method uses pattern recognition for the windshields and their surroundings
      to detect vehicles. However, the first method decreases the vehicle detection
      accuracy in winter season. To maintain high vehicle detection accuracy in all
      seasons, we developed the second method. The second method uses tires' thermal
      energy reflection areas on a road as the detection targets. The second method did
      not achieve high detection accuracy for vehicles on left-hand and right-hand
      lanes except for two center-lanes. Therefore, we have developed a new method
      based on the second method to increase the vehicle detection accuracy. This paper
      proposes the new method and shows that the detection accuracy for vehicles on all
      lanes is 92.1%. Therefore, by combining the first method and the new method, high
      vehicle detection accuracies are maintained under various environments, and road
      traffic flow surveillance can be realized. 

PMID- 25763383
TI  - Resistance to and accumulation of heavy metals by actinobacteria isolated from
      abandoned mining areas.
AB  - Accumulation of high concentrations of heavy metals in environments can cause
      many human health risks and serious ecological problems. Nowadays, bioremediation
      using microorganisms is receiving much attention due to their good performance.
      The aim of this work is to investigate heavy metals resistance and
      bioaccumulation potential of actinobacteria strains isolated from some abandoned
      mining areas. Analysis of mining residues revealed that high concentration of
      zinc "Zn" was recorded in Sidi Bouatman, Arbar, and Bir Nhass mining residues.
      The highest concentration of lead "Pb" was found in Sidi Bouatman. Copper "Cu,"
      cadmium "Cd," and chromium "Cr" were found with moderate and low concentrations.
      The resistance of 59 isolated actinobacteria to the five heavy metals was also
      determined. Using molecular identification 16S rRNA, these 27 isolates were found
      to belong to Streptomyces and Amycolatopsis genera. The results showed different
      levels of heavy metal resistance; the minimum inhibitory concentration (MIC)
      recorded was 0.55 for Pb, 0.15 for Cr, and 0.10 mg.mL(-1) for both Zn and Cu.
      Chemical precipitation assay of heavy metals using hydrogen sulfide technic (H2S)
      revealed that only 27 isolates have a strong ability to accumulate Pb (up to 600
      mg of Pb per g of biomass for Streptomyces sp. BN3). 

PMID- 25763386
TI  - The Australian Community Does Not Support Gender Selection by IVF for Social
      Reasons.
AB  - This study was carried out to determine the attitudes of the Australian community
      to IVF by a reliable community poll. Cross-sectional surveys, conducted by
      telephone of a random sample of 650 Australians were undertaken. The sample was
      drawn from the residential phone numbers in the Australian electronic "White
      Pages" and stratified by geographical area with quotas controlled by gender and
      age to be representative of the Australian population. The participants were
      asked to answer to three questions about gender selection, and their response was
      measured as "yes-allowed," "no-not allowed," or "undecided" for each of the
      questions. Whilst 91% of respondents supported the use of IVF to help infertile
      couples, only 20% supported gender selection within IVF or for family balancing.
      When it came to the use of IVF only for gender selection, only 17% were in
      favour. This survey shows that Australian community overwhelmingly opposes gender
      selection for social reasons. 

PMID- 25763385
TI  - The need for laparoscopic ovarian transposition in young patients with cervical
      cancer undergoing radiotherapy.
AB  - Maintaining the quality of life by preserving ovarian function in premenopausal
      patients with cervical cancer undergoing radiation is crucial. This can be
      accomplished with a simple and safe laparoscopic ovarian transposition procedure.
      This procedure aims to move the ovary out of the irradiation field, protecting it
      from direct radiation and irreversible damage and preserving its function.
      However, this procedure is often forgotten and seldom offered to patients. This
      review aims to lay stress on and reconsider the importance of laparoscopic
      ovarian transposition as a simple, safe, and extremely useful procedure. The
      biological effects of radiation are described briefly and several studies are
      evaluated, which reveal that this procedure has more benefits than risks. 

PMID- 25763387
TI  - Assessment of the reproductive health status of adult prison inmates in osun
      state, Nigeria.
AB  - Introduction. All over the world, numbers of prisoners have being increasing with
      majority in the sexually active age group; hence diseases such as HIV,
      Tuberculosis and Hepatitis are more prevalent in prisons than in the community.
      This study thus aims to provide an overview of the reproductive health status of
      adult prison inmates in Osun State. Methodology. This is a cross-sectional study
      among adult inmates in Osun State prison. Data was obtained from 209 selected
      respondents using pre-tested semi structured questionnaire. Result. Majority of
      the respondents were in the age group 20-39 years with mean age of 30.9 + 7.5.
      73.2% are aware of STIs, 93.3% HIV/AIDS and 81.3% contraception. 54.6% had
      multiple sexual partners before incarceration and 23.3% of them used condom
      always. 89.5% were not involved in any sexual practice inside the prison, 9.1%
      masturbated and 1.4% had homosexual partners. Less than 6% had access to male
      condoms gotten from prison staffs and prison clinics. Conclusion and
      recommendation. No comprehensive reproductive health care system to address
      reproductive health services in prisons. Respondents' knowledge about STIs,
      HIV/AIDS and contraception is good, but their condom usage is low compared with
      the knowledge. Government should put in place specific reproductive health
      programmes in prisons. 

PMID- 25763389
TI  - Comparative Analysis of Normal versus Fetal Growth Restriction in Pregnancy: The
      Significance of Maternal Body Mass Index, Nutritional Status, Anemia, and
      Ultrasonography Screening.
AB  - Fetal growth restriction or intrauterine growth restriction is one of the leading
      causes of perinatal mortality and morbidity in newborns. Fetal growth restriction
      is a complex multifactorial condition resulting from several fetal and maternal
      disorders. The objective of this study was twofold: first to examine the
      correlation between maternal parameters such as body mass index (BMI),
      nutritional status, anemia, and placental weight and diameter, and their effects
      on fetal growth and then to evaluate the effect of early screening by
      ultrasonography (USG) on the outcome of growth restricted pregnancies. In this
      study, 53 cases of fetal growth restriction were compared to 53 normal fetuses
      delivered in consecutive sequence. Growth restricted fetuses were delivered
      earlier in gestation, when compared with normal growth fetuses. Maternal anemia
      and malnutrition have significant association with the fetal growth restriction.
      Maternal anthropometry, such as low BMI, had effects on placental diameter and
      weight, which, in turn, adversely affected fetal weight. Thus, early USG
      screening along with robust screening for maternal BMI, nutritional status, and
      anemia can assist the obstetric team in providing early diagnosis, prompt
      intervention, and better outcome in pregnancy with fetal growth restriction. 

PMID- 25763390
TI  - Natural killer cells and their activation status in normal pregnancy.
AB  - Increased peripheral blood-activated NK cell counts are associated with increased
      risk of miscarriage and failed in vitro fertilization treatment. However,
      assessment of activated peripheral NK cells in normal and pathological
      pregnancies beyond implantation and early miscarriage has not been described.
      Total CD69 expressing NK cells counts were measured by flow cytometry in healthy
      women with singleton pregnancies, including 45 at 11(+6)-13(+6) weeks' gestation,
      46 at 20(+0)-22(+4) weeks, and 42 at 31(+6)-33(+5) weeks. The number of
      peripheral blood NK cells decreased, whereas the percentage of activated CD69
      expressing NK cells increased from the first to the third trimester of pregnancy.
      This study shows the course of peripheral blood NK cells and activated CD69
      expressing NK cells in uncomplicated nulliparous singleton pregnancies. This is a
      first step in understanding their implication in pathological pregnancies. 

PMID- 25763388
TI  - Metabolite Profiling in the Pursuit of Biomarkers for IVF Outcome: The Case for
      Metabolomics Studies.
AB  - Background. This paper presents the literature on biomarkers of in vitro
      fertilisation (IVF) outcome, demonstrating the progression of these studies
      towards metabolite profiling, specifically metabolomics. The need for more, and
      improved, metabolomics studies in the field of assisted conception is discussed.
      Methods. Searches were performed on ISI Web of Knowledge SM for literature
      associated with biomarkers of oocyte and embryo quality, and biomarkers of IVF
      outcome in embryo culture medium, follicular fluid (FF), and blood plasma in
      female mammals. Results. Metabolomics in the field of female reproduction is
      still in its infancy. Metabolomics investigations of embryo culture medium for
      embryo selection have been the most common, but only within the last five years.
      Only in 2012 has the first metabolomics investigation of FF for biomarkers of
      oocyte quality been reported. The only metabolomics studies of human blood plasma
      in this context have been aimed at identifying women with polycystic ovary
      syndrome (PCOS). Conclusions. Metabolomics is becoming more established in the
      field of assisted conception, but the studies performed so far have been
      preliminary and not all potential applications have yet been explored. With
      further improved metabolomics studies, the possibility of identifying a method
      for predicting IVF outcome may become a reality. 

PMID- 25763391
TI  - Randomized Comparison of Isosorbide Mononitrate and PGE2 Gel for Cervical
      Ripening at Term including High Risk Pregnancy.
AB  - Aims. Prostaglandin E2 is the most commonly used drug for cervical ripening prior
      to labour induction. However, there are concerns regarding uterine tachysystole
      and nonreassuring fetal heart (N-RFH). Isosorbide mononitrate (IMN) has been used
      successfully for cervical ripening. The present study was conducted to compare
      the two drugs for cervical ripening at term in hospital. Methods. Two hundred
      women with term pregnancies referred for induction of labour with Bishop score
      less than 6 were randomly allocated to receive either 40 mg IMN tablet vaginally
      (n = 100) or 0.5 mg PGE2 gel intracervically (n = 100). Adverse effects,
      progress, and outcomes of labour were assessed. Results. PGE2 group had
      significantly higher postripening mean Bishop score, shorter time from start of
      medication to vaginal delivery (13.37 +/- 10.67 hours versus 30.78 +/- 17.29
      hours), and shorter labour-delivery interval compared to IMN group (4.53 +/- 3.97
      hours versus 7.34 +/- 5.51 hours). However, PGE2 group also had significantly
      higher incidence of uterine tachysystole (15%) and N-RFH (11%) compared to none
      in IMN group, as well as higher caesarean section rate (27% versus 17%).
      Conclusions. Cervical ripening with IMN was less effective than PGE2 but resulted
      in fewer adverse effects and was safer especially in high risk pregnancies. 

PMID- 25763392
TI  - Theories on the pathogenesis of endometriosis.
AB  - Endometriosis is a common, chronic inflammatory disease defined by the presence
      of extrauterine endometrial tissue. The aetiology of endometriosis is complex and
      multifactorial, where several not fully confirmed theories describe its
      pathogenesis. This review examines existing theories on the initiation and
      propagation of different types of endometriotic lesions, as well as critically
      appraises the myriad of biologically relevant evidence that support or oppose
      each of the proposed theories. The current literature suggests that stem cells,
      dysfunctional immune response, genetic predisposition, and aberrant peritoneal
      environment may all be involved in the establishment and propagation of
      endometriotic lesions. An orchestrated scientific and clinical effort is needed
      to consider all factors involved in the pathogenesis of this multifaceted disease
      and to propose novel therapeutic targets to reach effective treatments for this
      distressing condition. 

PMID- 25763394
TI  - Body mass index and pregnancy outcome after assisted reproduction treatment.
AB  - The present study aimed to evaluate the impact of body mass index (BMI) on
      pregnancy outcome after intracytoplasmic sperm injection (ICSI). The study
      analyzed pregnancy outcome of 349 women who underwent ICSI by their BMI: <25, 25
      <30, and >=30 kg/m(2). The associations were generated by applying logistic
      regression models. A significant reduction in positive pregnancy outcome was
      observed among overweight and obese women (odds ratio (OR) = 0.50; 95% confidence
      interval (CI) = 0.25-0.99 for overweight women and OR = 0.45; 95% CI = 0.20-0.89
      for obese women). These estimates show that the pregnancy rates are reduced with
      increasing BMI. The effect of obesity on pregnancy outcome was absent when three
      and more embryos were transferred. Our study contributes to the reports linking
      overweight and obesity with decreased positive pregnancy outcome after ICSI and
      suggests women's age, infertility type, and number of embryos transferred to
      modify this reducing effect. 

PMID- 25763393
TI  - Impact of exogenous gonadotropin stimulation on circulatory and follicular fluid
      cytokine profiles.
AB  - Background. The natural cycle is the prototype to which we aspire to emulate in
      assisted reproduction techniques. Increasing evidence is emerging that controlled
      ovarian hyperstimulation (COH) with exogenous gonadotropins may be detrimental to
      oogenesis, embryo quality, and endometrial receptivity. This research aimed at
      assessing the impact of COH on the intrafollicular milieu by comparing follicular
      fluid (FF) cytokine profiles during stimulated in vitro fertilization (IVF) and
      modified natural cycle (MNC) IVF. Methods. Ten women undergoing COH IVF and 10
      matched women undergoing MNC IVF were recruited for this pilot study. 40 FF
      cytokine concentrations from individual follicles and plasma were measured by
      fluid-phase multiplex immunoassay. Demographic/cycle/cytokine data were compared
      and correlations between cytokines were computed. Results. No significant
      differences were found between COH and MNC groups for patient and cycle
      demographics, including outcome. Overall mean FF cytokine levels were higher in
      the MNC group for 29/40 cytokines, significantly so for leukaemia inhibitory
      factor and stromal cell-derived factor-1alpha. Furthermore, FF MNC cytokine
      correlations were significantly stronger than for COH data. Conclusions. These
      findings suggest that COH perturbs intrafollicular cytokine networks, in terms of
      both cytokine levels and their interrelationships. This may impact oocyte
      maturation/fertilization and embryo developmental competence. 

PMID- 25763395
TI  - An audit of indications, complications, and justification of hysterectomies at a
      teaching hospital in India.
AB  - Objective. Aim of this audit was to analyze indications, complications, and
      correlation of preoperative diagnosis with final histopathology report of all
      hysterectomies, performed in a premier teaching hospital. Methods. Present study
      involved all patients who underwent hysterectomy at a premier university hospital
      in Southern India, in one year (from 1 January, 2012, to 31 December, 2012).
      Results. Most common surgical approach was abdominal (74.7%), followed by vaginal
      (17.8%), and laparoscopic (6.6%) hysterectomy. Most common indication for
      hysterectomy was symptomatic fibroid uterus (39.9%), followed by uterovaginal
      prolapse (16.3%). Overall complication rate was 8.5%. Around 84% had the same
      pathology as suspected preoperatively. Only 6 (5 with preoperative diagnosis of
      abnormal uterine bleeding and one with high grade premalignant cervical lesion)
      had no significant pathology in their hysterectomy specimen. Conclusion.
      Hysterectomy is used commonly to improve the quality of life; however at times it
      is a lifesaving procedure. As any surgical procedure is associated with a risk of
      complications, the indication should be carefully evaluated. With the emergence
      of many conservative approaches to deal with benign gynecological conditions, it
      is prudent to discuss available options with the patient before taking a direct
      decision of surgically removing her uterus. 

PMID- 25763396
TI  - The Desire for Multiple Pregnancy among Patients with Infertility and Their
      Partners.
AB  - Objective. To study the predictors for desire for multiple pregnancies and the
      influence of providing information regarding the maternal and fetal complications
      associated with multiple pregnancies on their preference for multiple
      pregnancies. Methods. Couples attending an infertility clinic were offered to
      fill up a questionnaire separately. Following this, they were handed a pamphlet
      with information regarding the risks associated with multiple pregnancies. The
      patients will then be required to answer the question on the number of
      pregnancies desired again. Results. Two hundred fifty three out of 300
      respondents completed the questionnaires adequately. A higher proportion of
      respondents, 60.3% of females and 57.9% of males, prefer singleton pregnancy.
      Patients who are younger than 35 years, with preexisting knowledge of risks
      associated with multiple pregnancies and previous treatment for infertility, have
      decreased desire for multiple pregnancies. However, for patients who are older
      than 35, with longer duration of infertility, and those patients who have
      preexisting knowledge of the increased risk, providing further information
      regarding the risks did not change their initial preferences. Conclusion.
      Providing and reinforcing knowledge on the risks to mother and fetus associated
      with multiple pregnancies did not decrease the preference for multiple
      pregnancies in patients. 

PMID- 25763397
TI  - Knowledge, Attitude, and Preventive Practices among Prison Inmates in Ogbomoso
      Prison at Oyo State, South West Nigeria.
AB  - Prisoners are at special risk for infection with human immunodeficiency virus
      (HIV) because of overcrowded prisons, unprotected sex and sexual assault,
      occurrence of sexual practices that are risky to health, unsafe injecting
      practices, and inadequate HIV prevention, care, and support services. This study
      aimed to describe the knowledge, attitude, and preventive practices towards
      HIV/AIDS by male inmates in Ogbomoso Prison at Oyo State, South West Nigeria.
      This was a cross-sectional study. A simple random sampling method was employed to
      select 167 male participants and data were collected using pretested structured
      interviewer-administered questionnaire. The data were collated and analyzed using
      the Statistical Package for Social Sciences version 17. Fifty (29.9%) were in the
      age group 20-24 years with mean age of 30.99 +/- 11.41. About half (50.3%) had
      been married before incarceration. Family and friends (30%), health care workers
      (25%), prison staff (20%), and mass media (25%) were the commonest sources of
      information on HIV/AIDS. Knowledge about HIV was found to be high (94.6%). About
      68.9% believed that people with the disease should be avoided. The knowledge
      about HIV/AIDS among inmates was high, but misconceptions about HIV/AIDS are
      still rife among the prisoners and educational programs would be required to
      correct this. 

PMID- 25763398
TI  - Comparison of results of cycles treated with modified mild protocol and short
      protocol for ovarian stimulation.
AB  - The ovarian stimulation has been applied in order to increase the number of
      oocytes to compensate for the poor results of in vitro fertilization, allowing
      the selection of one or more embryos to be transferred. Our aim is to compare the
      results obtained in IVF/ICSI cycles using the short protocol for controlled
      ovarian stimulation to the results from the modified mild protocol used in our
      department. A total of 240 cycles were conducted from January 2010 to December
      2011. When comparing both protocols, it could be observed that there was a
      significant difference in the quantity of gonadotropins doses in the mild
      protocol and in the short protocol. No significant difference was observed
      regarding pregnancy rates per cycle, 22% and 26.2%, in short and mild protocols,
      respectively. The protocols of controlled ovarian stimulation are often
      associated with high risk of complications such as ovarian hyperstimulation
      syndrome, excessive emotional stress, high rates of treatment dropouts, and
      abdominal discomfort. With the data obtained in this study, one can conclude that
      there are less risks and complications for the patient when using the mild
      stimulation protocol. It was also observed that in this group there was a
      slightly higher rate. 

PMID- 25763399
TI  - The chromosomal constitution of embryos arising from monopronuclear oocytes in
      programmes of assisted reproduction.
AB  - The assessment of oocytes showing only one pronucleus during assisted
      reproduction is associated with uncertainty. A compilation of data on the genetic
      constitution of different developmental stages shows that affected oocytes are
      able to develop into haploid, diploid, and mosaic embryos with more or less
      complex chromosomal compositions. In the majority of cases (~80%), haploidy
      appears to be caused by gynogenesis, whereas parthenogenesis or androgenesis is
      less common. Most of the diploid embryos result from a fertilization event
      involving asynchronous formation of the two pronuclei or pronuclear fusion at a
      very early stage. Uniparental diploidy may sometimes occur if one pronucleus
      fails to develop and the other pronucleus already contains a diploid genome or
      alternatively a haploid genome undergoes endoreduplication. In general, the
      chance of obtaining a biparental diploid embryo appears higher after conventional
      in vitro fertilization than after intracytoplasmic sperm injection. If a transfer
      of embryos obtained from monopronuclear oocytes is envisaged, it should be tried
      to culture them up to the blastocyst since most haploid embryos are not able to
      reach this stage. Comprehensive counselling of patients on potential risks is
      advisable before transfer and a preimplantation genetic diagnosis could be
      offered if available. 

PMID- 25763400
TI  - Total laparoscopic hysterectomy with prior uterine artery ligation at its origin.
AB  - We compared the duration of surgery, blood loss, and complications between
      patients in whom both uterine arteries were ligated at the beginning of total
      laparoscopic hysterectomy (TLH) and patients in whom ligation was done after
      cornual pedicle. Using a prospective study in a gynecologic laparoscopic center,
      a total of 52 women who underwent TLH from June 2013 to January 2014 were
      assigned into two groups. In group A, uterine arteries were ligated after the
      cornual pedicles as done conventionally. In group B, TLH was done by ligating
      both uterine arteries at the beginning of the procedure. All the other pedicles
      were desiccated using harmonic scalpel or bipolar diathermy. Uterus with cervix
      was removed vaginally or by morcellation. The indication for TLH was
      predominantly dysfunctional uterine bleeding and myomas in both groups. In group
      A, the average duration of surgery was 71 minutes, when compared to 60 minutes in
      group B (P < 0.001). In group A, the total blood loss was 70 mL, when compared to
      43#x2009;mL in group B (P value < 0.001). There were no major complications in
      both groups. To conclude, prior uterine artery ligation at its origin during TLH
      reduces the blood loss and surgical duration as well as the complications during
      surgery. 

PMID- 25763401
TI  - Adequacy of the endometrial samples obtained by the uterine explora device and
      conventional dilatation and curettage: a comparative study.
AB  - Aims. Our aim is to compare the adequacy and diagnostic yield of samples obtained
      by the endometrial Explora Sampler I-MX120 with endometrial specimens obtained by
      conventional dilatation and curettage (D&C). Methods. A total of 1270 endometrial
      samples were received in the histopathology laboratories at the King Khalid
      University Hospital, Riyadh, Saudi Arabia, between 2007 and 2010. In the
      outpatient clinic, the Uterine Explora Model I was used to obtain 996 samples.
      The remaining 274 samples were obtained by conventional D&C. Sample adequacy and
      the clustering of inadequate specimens according to age groups by the two
      different techniques were compared and statistically analyzed. Results. Out of
      1270 endometrial samples, 253 (19.9%) were inadequate. The Uterine Explora was
      used in 88.5% of these inadequate samples (253 samples), and the remaining 11.5%
      were obtained by D&C. The insufficient tissue incidence was higher with the
      Explora (17.6%) than with the D&C (2.2%) and the difference was statistically
      significant (P < 0.0001). The ages of the patients, as well as the clinical
      indications for the procedures, were recorded. Conclusion. This retrospective
      study demonstrated better specimen adequacy when D&C was used compared to the
      higher rate of sample insufficiency obtained with the Explora. 

PMID- 25763402
TI  - Feasibility, acceptability, and programme effectiveness of misoprostol for
      prevention of postpartum haemorrhage in rural bangladesh: a quasiexperimental
      study.
AB  - We explored the feasibility of distributing misoprostol tablets using two
      strategies in prevention of postpartum haemorrhage (PPH) among women residing in
      the Abhoynagar subdistrict of Bangladesh. We conducted a quasiexperimental study
      with a posttest design and nonequivalent comparison and intervention groups.
      Paramedics distributed three misoprostol tablets, one delivery mat (Quaiyum's
      delivery mat), a packet of five standardized sanitary pads, and one lidded
      plastic container with detailed counseling on their use. All materials except
      misoprostol were also provided with counseling sessions to the control group
      participants. Postpartum blood loss was measured by paramedics using standardized
      method. This study has demonstrated community acceptability to misoprostol
      tablets for the prevention of PPH that reduced overall volume of blood loss after
      childbirth. Likewise, the delivery mat and pad were found to be useful to mothers
      as tools for assessing the amount of blood loss after delivery and informing care
      seeking decisions. Further studies should be undertaken to explore whether
      government outreach health workers can be trained to effectively distribute
      misoprostol tablets among rural women of Bangladesh. Such a study should explore
      and identify the programmatic requirements to integrate this within the existing
      reproductive health program of the Government of Bangladesh. 

PMID- 25763403
TI  - Comparison of IVF Outcomes between Minimal Stimulation and High-Dose Stimulation
      for Patients with Poor Ovarian Reserve.
AB  - We examined whether treatment with minimum-dose stimulation (MS) protocol
      enhances clinical pregnancy rates compared to high-dose stimulation (HS)
      protocol. A retrospective cohort study was performed comparing IVF and pregnancy
      outcomes between MS and HS gonadotropin-antagonist protocol for patients with
      poor ovarian reserve (POR). Inclusion criteria included patients with an anti
      Mullerian hormone (AMH) <=8 pmol/L and/or antral follicle count (AFC) <=5 on days
      2-3 of the cycle. Patients from 2008 exclusively had a HS protocol treatment,
      while patients in 2010 had treatment with a MS protocol exclusively. The MS
      protocol involved letrozole at 2.5 mg over 5 days, starting from day 2,
      overlapping with gonadotropins, starting from the third day of letrozole at 150
      units daily. GnRH antagonist was introduced once one or more follicles reached 14
      mm or larger. The HS group received gonadotropins (>=300 IU/day) throughout their
      antagonist cycle. Clinical pregnancy rate was significantly higher in the MS
      protocol compared to the HS protocol (P = 0.007). Furthermore, the live birth
      rate was significantly higher in the MS group compare to the HS group (P =
      0.034). In conclusion, the MS IVF protocol is less expensive (lower gonadotropin
      dosage) and resulted in a higher clinical pregnancy rate and live birth rate than
      a HS protocol for poor responders. 

PMID- 25763404
TI  - Correlation between Abortion and Infertility among Nonsmoking Women with a
      History of Passive Smoking in Childhood and Adolescence.
AB  - The aim of this study is to evaluate the correlation of exposing to the cigarette
      smoke in childhood and adolescence with infertility and abortion in women. This
      case-control study evaluated 178 women who had been attended to at the Amir-al
      Momenin Hospital in Tehran in 2012-2013. Seventy-eight women with chief complaint
      of abortion, infertility, and missed abortion and 100 healthy women were
      considered as case and control groups, respectively. The tool was a questionnaire
      with two parts. In the first part demographic information was gathered and in the
      second part the information regarding the history of passive smoking in childhood
      and adolescence period, abortion, and infertility was gathered. The mean age in
      case and control groups was 26.24 +/- 3.1 and 27.3 +/- 4.2 years, respectively.
      The mean body mass index (BMI) was 25.74 +/- 1.38 Kg/m(2). Abortion rates among
      passive smoker and nonpassive smoker patients were statistically significant (P =
      0.036). Based on findings of this study, the experience of being a passive smoker
      in childhood and adolescence in women will increase the risk of abortion and
      infertility in the future, which could be the reason to encourage the society to
      step back from smoking cigarettes. 

PMID- 25763407
TI  - A Comparative Study of Prevalence of RTI/STI Symptoms and Treatment Seeking
      Behaviour among the Married Women in Urban and Rural Areas of Delhi.
AB  - Background. In developing countries, women are at high risk for several
      reproductive health problems especially RTI/STIs. Since all RTIs/ STIs are
      preventable and most of them are curable, it is pertinent to study the
      determinants of the health seeking behaviour. Objectives. To compare the
      prevalence and treatment seeking behaviour about RTI/STI symptoms among the
      married women of reproductive age group (18-45 years) living in urban and rural
      area of Delhi. Methods. A cross-sectional study was done among the married women
      of reproductive age group residing in Pooth Khurd, a village in North West
      district of Delhi, and Delhi Gate, an urban locality situated in central Delhi.
      Results. In this study, the prevalence of RTI/STI symptoms was found to be
      similar in both urban (42.3%) and rural area (42%). In urban area, 73% sought
      treatment, while in rural area only 45.6% sought treatment. Prevalence of the
      symptoms was found to be higher among the study subjects who were not using any
      contraceptive method, had history of abortion, and were with lower educational
      status, in both urban and rural areas. Treatment seeking behaviour was
      significantly higher among the educated women, contraceptive users, and older age
      group women in both rural and urban area. 

PMID- 25763408
TI  - Predictive value of middle cerebral artery to uterine artery pulsatility index
      ratio in hypertensive disorders of pregnancy.
AB  - Aims and Objectives. (i) To determine the predictive value of cerebrouterine (CU)
      ratio (middle cerebral artery to uterine artery pulsatility index, MCA/UT PI) in
      assessing perinatal outcome among hypertensive disorders of pregnancy. (ii) To
      compare between CU ratio and CP ratio (MCA/Umbilical artery PI) as a predictor of
      adverse perinatal outcome. Methods. A prospective observational study was done in
      a tertiary medical college hospital, from September 2012 to August 2013. One
      hundred singleton pregnancies complicated by hypertension peculiar to pregnancy
      were enrolled. Both CU and CP ratios were estimated. The perinatal outcomes were
      studied. Results. Both cerebrouterine and cerebroplacental ratios had a better
      negative predictive value in predicting adverse perinatal outcome. However, both
      CU and CP ratios when applied together were able to predict adverse outcomes
      better than individual ratios. The sensitivity, specificity, positive predictive
      value, and the negative predictive values for an adverse neonatal outcome with CU
      ratio were 61.3%, 70.3%, 56%, and 78.9%, respectively, compared to 42%, 57.5%,
      62%, and 76% as with CP ratio. Conclusion. Cerebrouterine ratio and
      cerebroplacental ratio were complementary to each other in predicting the adverse
      perinatal outcomes. Individually, both ratios were reassuring for favorable
      perinatal outcome with high negative predictive value. 

PMID- 25763405
TI  - Polycystic ovary syndrome, insulin resistance, and obesity: navigating the
      pathophysiologic labyrinth.
AB  - Polycystic ovary syndrome (PCOS) is a highly prevalent endocrine-metabolic
      disorder that implies various severe consequences to female health, including
      alarming rates of infertility. Although its exact etiology remains elusive, it is
      known to feature several hormonal disturbances, including hyperandrogenemia,
      insulin resistance (IR), and hyperinsulinemia. Insulin appears to disrupt all
      components of the hypothalamus-hypophysis-ovary axis, and ovarian tissue insulin
      resistance results in impaired metabolic signaling but intact mitogenic and
      steroidogenic activity, favoring hyperandrogenemia, which appears to be the main
      culprit of the clinical picture in PCOS. In turn, androgens may lead back to IR
      by increasing levels of free fatty acids and modifying muscle tissue composition
      and functionality, perpetuating this IR-hyperinsulinemia-hyperandrogenemia cycle.
      Nonobese women with PCOS showcase several differential features, with unique
      biochemical and hormonal profiles. Nevertheless, lean and obese patients have
      chronic inflammation mediating the long term cardiometabolic complications and
      comorbidities observed in women with PCOS, including dyslipidemia, metabolic
      syndrome, type 2 diabetes mellitus, and cardiovascular disease. Given these
      severe implications, it is important to thoroughly understand the
      pathophysiologic interconnections underlying PCOS, in order to provide superior
      therapeutic strategies and warrant improved quality of life to women with this
      syndrome. 

PMID- 25763409
TI  - Incidence and correlates of maternal near miss in southeast iran.
AB  - This prospective study aimed to estimate the incidence and associated factors of
      severe maternal morbidity in southeast Iran. During a 9-month period in 2013, all
      women referring to eight hospitals for termination of pregnancy as well as women
      admitted during 42 days after the termination of pregnancy were enrolled into the
      study. Maternal near miss conditions were defined based on Say et al.'s
      recommendations. Five hundred and one cases of maternal near miss and 19,908 live
      births occurred in the study period, yielding a maternal near miss ratio of 25.2
      per 1000 live births. This rate was 7.5 and 105 per 1000 in private and tertiary
      care settings, respectively. The rate of maternal death in near miss cases was
      0.40% with a case:fatality ratio of 250 : 1. The most prevalent causes of near
      miss were severe preeclampsia (27.3%), ectopic pregnancy (18.4%), and abruptio
      placentae (16.2%). Higher age, higher education, and being primiparous were
      associated with a higher risk of near miss. Considering the high rate of maternal
      near miss in referral hospitals, maternal near miss surveillance system should be
      set up in these hospitals to identify cases of severe maternal morbidity as soon
      as possible. 

PMID- 25763406
TI  - The Role of Metformin in Metabolic Disturbances during Pregnancy: Polycystic
      Ovary Syndrome and Gestational Diabetes Mellitus.
AB  - Maintenance of gestation implicates complex function of multiple endocrine
      mechanisms, and disruptions of the global metabolic environment prompt profound
      consequences on fetomaternal well-being during pregnancy and postpartum.
      Polycystic Ovary Syndrome (PCOS) and gestational diabetes mellitus (GDM) are very
      frequent conditions which increase risk for pregnancy complications, including
      early pregnancy loss, pregnancy-induced hypertensive disorders, and preterm
      labor, among many others. Insulin resistance (IR) plays a pivotal role in the
      pathogenesis of both PCOS and GDM, representing an important therapeutic target,
      with metformin being the most widely prescribed insulin-sensitizing antidiabetic
      drug. Although traditional views neglect use of oral antidiabetic agents during
      pregnancy, increasing evidence of safety during gestation has led to metformin
      now being recognized as a valuable tool in prevention of IR-related pregnancy
      complications and management of GDM. Metformin has been demonstrated to reduce
      rates of early pregnancy loss and onset of GDM in women with PCOS, and it appears
      to offer better metabolic control than insulin and other oral antidiabetic drugs
      during pregnancy. This review aims to summarize key aspects of current evidence
      concerning molecular and epidemiological knowledge on metformin use during
      pregnancy in the setting of PCOS and GDM. 

PMID- 25763410
TI  - Responses of dental pulp cells to a less invasive bleaching technique applied to
      adhesive-restored teeth.
AB  - PURPOSE: To assess the cytotoxicity of 35% hydrogen peroxide (HP) bleaching gel
      applied for 15 min to sound or restored teeth with two-step self-etching adhesive
      systems and composite resin. MATERIALS AND METHODS: Sound and restored
      enamel/dentin disks were stored in water for 24 h or 6 months + thermocycling.
      The disks were adapted to artificial pulp chambers and placed in compartments
      containing culture medium. Immediately after bleaching, the culture medium in
      contact with dentin was applied for 1 h to previously cultured odontoblast-like
      MDPC-23 cells. Thereafter, cell viability (MTT assay) and morphology (SEM) were
      assessed. Data were analyzed by two-way ANOVA and Tukey's test (a = 5%). RESULTS:
      In comparison to the negative control group (no treatment), no significant cell
      viability reduction occurred in those groups in which sound teeth were bleached.
      However, a significant decrease in cell viability was observed in the adhesive
      restored bleached groups compared to negative control. No significant difference
      among bleached groups was observed with respect to the presence of restoration
      and storage time. CONCLUSION: The application of 35% HP bleaching gel to sound
      teeth for 15 min does not cause toxic effects in pulp cells. When this bleaching
      protocol was performed in adhesive-restored teeth, a significant toxic effect
      occurred.

PMID- 25763411
TI  - Analyte induced water adsorbability in gas phase biosensors: the influence of
      ethinylestradiol on the water binding protein capacity.
AB  - An ultra-sensitive gas phase biosensor/tracer/bio-sniffer is an emerging
      technology platform designed to provide real-time information on air-borne
      analytes, or those in liquids, through classical headspace analysis. The desired
      bio-sniffer measures gaseous 17alpha- ethinylestradiol (ETED) as frequency
      changes on a quartz crystal microbalance (QCM), which is a result of the
      interactions of liquid sample components in the headspace (ETED and water) with a
      biorecognition layer. The latter was constructed by immobilization of polyclonal
      antiserum against a phenolic A-ring of estrogenic receptors through protein A.
      The QCM response exhibited stretched exponential kinetics of negative frequency
      shifts with reversible and "irreversible" components of mass uptake onto the
      sensor surface in static headspace conditions when exposed to water solutions of
      ETED over the sensor working range, from 10(-10) to 10(-17) g L(-1). It was shown
      that the variations in the QCM response characteristics are due to the change of
      the water-binding capacity of the sensing layer induced by protein
      transformations initiated by the binding of ETED molecules. This result is well
      correlated with the natural physiological function of estrogens in controlling
      the homeostasis of body fluids in living beings. 

PMID- 25763412
TI  - Nanomaterial-based biosensors using dual transducing elements for solution phase
      detection.
AB  - Biosensors incorporating nanomaterials have demonstrated superior performance
      compared to their conventional counterparts. Most reported sensors use
      nanomaterials as a single transducer of signals, while biosensor designs using
      dual transducing elements have emerged as new approaches to further improve
      overall sensing performance. This review focuses on recent developments in
      nanomaterial-based biosensors using dual transducing elements for solution phase
      detection. The review begins with a brief introduction of the commonly used
      nanomaterial transducers suitable for designing dual element sensors, including
      quantum dots, metal nanoparticles, upconversion nanoparticles, graphene, graphene
      oxide, carbon nanotubes, and carbon nanodots. This is followed by the
      presentation of the four basic design principles, namely Forster Resonance Energy
      Transfer (FRET), Amplified Fluorescence Polarization (AFP), Bio-barcode Assay
      (BCA) and Chemiluminescence (CL), involving either two kinds of nanomaterials, or
      one nanomaterial and an organic luminescent agent (e.g. organic dyes, luminescent
      polymers) as dual transducers. Biomolecular and chemical analytes or biological
      interactions are detected by their control of the assembly and disassembly of the
      two transducing elements that change the distance between them, the size of the
      fluorophore-containing composite, or the catalytic properties of the nanomaterial
      transducers, among other property changes. Comparative discussions on their
      respective design rules and overall performances are presented afterwards.
      Compared with the single transducer biosensor design, such a dual-transducer
      configuration exhibits much enhanced flexibility and design versatility, allowing
      biosensors to be more specifically devised for various purposes. The review ends
      by highlighting some of the further development opportunities in this field. 

PMID- 25763413
TI  - H(+)-Assisted fluorescent differentiation of Cu(+) and Cu(2+): effect of Al(3+)
      induced acidity on chemical sensing and generation of two novel and independent
      logic gating pathways.
AB  - A novel Schiff base probe exhibited strong 'turn-ON' fluorescence for Cu(2+) at
      345 nm, Al(3+) at 445 nm, and Cu(+) at 360 nm in the presence of Al(3+) in
      organic solvent (acetonitrile), which allowed for construction of molecular logic
      gates 'INH' and '1:2 DEMULTIPLEXING.' H(+) generated from Al(3+) contributed
      greatly to Cu(+) chemosensing based on a redox non-innocence mechanism. 

PMID- 25763414
TI  - Fluorescence turn-on detection of glucose via the Ag nanoparticle mediated
      release of a perylene probe.
AB  - A novel fluorescence turn-on strategy for glucose sensing is demonstrated. The
      fluorescence of a perylene probe could be quenched by the silver nanoparticles
      (Ag NPs). The Ag NPs could be etched by H2O2 generated from the enzymatic
      oxidation of glucose. And efficient probe fluorescence recovery was detected. 

PMID- 25763415
TI  - Capacitance spectroscopy and density functional theory.
AB  - The redox capacitance and its associated quantum component arising from the
      charging of molecular levels from coupled metallic states are resolvable and
      quantified experimentally by capacitance spectroscopy (CS). Herein we relate both
      this N-electron system capacitance directly to conceptual chemistry density
      functional theory (DFT) and the charging magnitude and associated quantum
      capacitive term (which resemble those introduced by Serge Luryi) to the Kohn-Sham
      frontier molecular orbital associated energies for isolated molecules and DFT
      calculated redox density of states (DOS) at metal-molecule junctions for a single
      molecule and molecular films confined at metallic interfaces. DFT computational
      analyses reveal the orbital energetic alignment between the iron redox site and
      those states in the metal specifically when metal-molecule junctions are formed.
      The impact of this on the resolved chemical softness and capacitance is also
      revealed. These analyses, additionally, are shown to numerically resolve redox
      capacitance in a manner that accurately reproduces experimental observations for
      molecular films. These observations both theoretically underpin CS and provide
      guidance on its optimised application in interfacial analyses involving molecular
      electrochemistry and derived sensory applications. 

PMID- 25763416
TI  - Reaginic antibodies.

PMID- 25763417
TI  - Zoon's balanitis.
AB  - Zoon's balanitis, is typically found in older, uncircumcised males and can be
      asymptomatic, pruritic, or cause dysuria. The typical appearance is erythematous,
      discrete, moist plaques with a "cayenne pepper" speckled appearance and an orange
      hue on the glans penis and sometimes prepuce, which may display "kissing lesions"
      on areas that are in direct contact with the lesions.These may eventually erode
      and leave a "rusty stain". Histologically, these have a dense lichenoid
      infiltrate in the upper and mid dermis with abundant plasma cells.

PMID- 25763418
TI  - Guidelines for diagnosis, prevention and treatment of hand eczema.
AB  - The guidelines aim to provide advice on the management of hand eczema (HE), using
      an evidence- and consensus-based approach. The guidelines consider a systematic
      Cochrane review on interventions for HE, which is based on a systematic search of
      the published literature (including hand-searching). In addition to the evidence-
      and consensus-based recommendation on the treatment of HE, the guidelines cover
      mainly consensus-based diagnostic aspects and preventive measures (primary and
      secondary prevention). Treatment recommendations include non-pharmacological
      interventions, topical, physical and systemic treatments. Topical corticosteroids
      are recommended as first line treatment in the management of HE, however
      continuous long-term treatment beyond six weeks only when necessary and under
      careful me-dical supervision. Alitretinoin is recommended as a second line
      treatment (relative to topical corticosteroids) for patients with severe chronic
      HE. Randomized control trials (RCT) are missing for other used systemic
      treatments and comparison of systemic drugs in "head-to-head" RCTs are needed.The
      guidelines development group is a working group of the European Society of
      Contact Dermatitis (ESCD) and has carefully tried to reconcile opposite views,
      define current optimal practice and provide specific recommendations, and
      meetings have been chaired by a professional moderator of the AWMF
      (Arbeitsgemeinschaft der Wis-senschaftlichen Medizinischen Fachgesellschaften;
      Association of the Scientific Medi-cal Societies in Germany).No financial support
      was given by any medical company. The guidelines are expected to be valid until
      December 2017 at the latest.

PMID- 25763419
TI  - [Murine typhus is still present].

PMID- 25763420
TI  - [Appendicitis is still severe].

PMID- 25763421
TI  - [Poliomyelitis persistence].

PMID- 25763422
TI  - [Frequency of animal bites].

PMID- 25763423
TI  - [Trichinella papuae: a new species].

PMID- 25763424
TI  - [Antihelmintics and Trichocephalus].

PMID- 25763425
TI  - Retraction notice to "Thalidomide treatment attenuates  chemotherapy-induced
      gonadal toxicity.

PMID- 25763426
TI  - Nail-patella syndrome.

PMID- 25763427
TI  - Interpretation and expectations among mothers of children with anxiety disorders:
      associations with maternal anxiety disorder.
AB  - BACKGROUND: Models of the development and maintenance of childhood anxiety
      suggest an important role for parent cognitions: that is, negative expectations
      of children's coping abilities lead to parenting behaviors that maintain child
      anxiety. The primary aims of the current study were to (1) compare expectations
      of child vulnerability and coping among mothers of children with anxiety
      disorders on the basis of whether or not mothers also had a current anxiety
      disorder, and (2) examine the degree to which the association between maternal
      anxiety disorder status and child coping expectations was mediated by how mothers
      interpreted ambiguous material that referred to their own experience. METHODS:
      The association between interpretations of threat, negative emotion, and control
      was assessed using hypothetical ambiguous scenarios in a sample of 271 anxious
      and nonanxious mothers of 7- to 12-year-old children with an anxiety disorder.
      Mothers also rated their expectations when presented with real life challenge
      tasks. RESULTS: There was a significant association between maternal anxiety
      disorder status and negative expectations of child coping behaviors. Mothers'
      self-referent interpretations were found to mediate this relationship. Responses
      to ambiguous hypothetical scenarios correlated significantly with responses to
      real life challenge tasks. CONCLUSIONS: Treatments for childhood anxiety
      disorders in the context of parental anxiety disorders may benefit from the
      inclusion of a component to directly address parental cognitions. Some
      inconsistencies were found when comparing maternal expectations in response to
      hypothetical scenarios with real life challenges. This should be addressed in
      future research.

PMID- 25763428
TI  - Response.

PMID- 25763429
TI  - Response.

PMID- 25763430
TI  - Response.

PMID- 25763431
TI  - Author response.

PMID- 25763432
TI  - Author response.

PMID- 25763433
TI  - Response.

PMID- 25763434
TI  - Response.

PMID- 25763435
TI  - Response.

PMID- 25763437
TI  - Recurrent atrial fibrillation reduced after renal  denervation with pulmonary
      vein ablation  in select patients.

PMID- 25763436
TI  - Genetic evolution of equine influenza strains isolated in France  from 2005 to
      2010.
AB  - REASON FOR PERFORMING THIS STUDY: Equine influenza virus (EIV) is considered the
      most economically important equine respiratory pathogen worldwide. The H3N8
      subtype, responsible for all outbreaks of equine influenza globally, evolves
      perpetually. Mutations in the genome of these viruses have the potential to
      modify their antigenic properties and recognition by pre-existing antibodies.
      OBJECTIVES: The aim of this study was to determine the genetic evolution of EIV
      strains in France and to compare it with the evolution of strains isolated
      globally. Analysis of the sequence data was performed to investigate any possible
      links between the outbreaks. STUDY DESIGN: Retrospective genetic analysis study
      of archived material. METHODS: Analyses were performed on the HA1 domain of
      haemagglutinin H3 of EIV isolated in a previous study carried out from November
      2005 to October 2010. The nucleic acid sequence of 41 strains was analysed and
      translated. The French viruses were compared with 59 Clade 1 strains and 83 Clade
      2 strains. Strains were aligned chronologically and on the basis of their
      geographical origin. RESULTS: The 16 Clade 1 strains are all derived from the
      outbreak that started in the Grosbois training yard in 2009. The virus genome
      appears to have been stable during the outbreak. The 25 Clade 2 strains were
      isolated over the 5-year period during which several mutations had emerged. Some
      strains incorporate a sporadic mutation, and others a mutation that may occur
      several times but does not persist. However, all strains are gradually moving
      towards definitive mutations. CONCLUSION: This study demonstrated that EIVs have
      evolved in France during this period in a similar manner to EIVs globally. The
      data lend support to the current World Animal Health Organisation recommendation
      that the vaccines contain a representative of both Clade 1 and Clade 2 of the
      Florida sublineage.

PMID- 25763438
TI  - Newmethod predicts optimal number and  location of automated external
      defibrillators:   a new innovation was presented atESC Congress 2014 by Dr
      Benjamin  Dahan from France.

PMID- 25763439
TI  - HIGHCARE: the HIGH altitude CArdiovascular  Research study:    a scientific
      expedition on Mount Everest to measure the effects   of altitude on blood
      pressure.

PMID- 25763440
TI  - The Istituto Auxologico Italiano:   an institute in Italy dedicated to biomedical
      research   and health care.

PMID- 25763441
TI  - American Medical News production discontinued:   the print and online news
      publication of the American Medical   Association has closed its doors due to
      declining advertising revenue   and an unsustainable business model.

PMID- 25763442
TI  - What in your view is the best cardiology   innovation of the last decade?  Four
      cardiologists from Africa, Europe, and India give their opinion.

PMID- 25763443
TI  - Words of wisdom. Re: PSA density improves prediction of prostate cancer.

PMID- 25763444
TI  - Words of wisdom: re: long-term testosterone therapy in hypogonadal men
      ameliorates elements of the metabolic syndrome:an observational, long-term
      registry study.

PMID- 25763446
TI  - Words of wisdom. Re: low grade micropapillary urothelial carcinoma,does it exist?
      -Analysis of management and outcomes from the Surveillance, Epidemiology and End
      Results (SEER) database.

PMID- 25763445
TI  - Words of wisdom. Re: urine is not sterile: use of enhanced urine culture
      techniques to detect resident bacterial flora in the adult female bladder.

PMID- 25763447
TI  - Words of wisdom. Re: prognostic factors and risk groups in T1G3 non-muscle
      invasive bladder cancer patients initially treated with Bacillus Calmette-Guerin:
      results of a retrospective multicenter study of 2451 patients.

PMID- 25763448
TI  - Arrhythmia in cardiac sarcoidosis.

PMID- 25763453
TI  - Total synthesis and structural revision of mycalol, an anticancer natural product
      from the marine source.
AB  - The total synthesis of an anticancer (anaplastic thyroid) natural lipid mycalol
      has been accomplished for the first time. Synthesis of originally proposed
      structure necessitated the revision of structure in which the position of acetate
      group moved from C20 to C19 and a change in stereochemistry of the glycerol unit.

PMID- 25763454
TI  - Characterization of pharmacy services in Portuguese prisons: a national survey.
AB  - PURPOSE: The primary purpose of this paper is to collect reliable information to
      characterize the pharmacy services in Portuguese prisons. The secondary purpose
      is to develop a set of suggestions for improving these services and, therefore,
      improve the health services provided to the inmate population.
      DESIGN/METHODOLOGY/APPROACH: A three pages survey was developed that included
      questions covering the characterization of prison health teams, pharmacy services
      and pharmacy activities. This survey was sent to all Portuguese prisons, with
      capacity higher than 50 prisoners. The response rate was of 87.5 per cent.
      FINDINGS: It was found that only 6.1 per cent of prisons had pharmacists and that
      in 63 per cent the guards still participated in pharmacy activities. There were
      not Pharmacy and Therapeutics Committees in 94 per cent of prisons and 94.4 per
      cent did not present adequate storage conditions for drugs. Only 51.7 per cent of
      prisons had computers in the pharmacy and only 3.4 per cent had access to the
      internet. This study found that there is a gap between public and prison pharmacy
      services, since most prison pharmacies in Portugal are solely locals of storage
      and distribution of drugs, with no effective management nor promotion of drug
      rational use. ORIGINALITY/VALUE: This paper is the first study about pharmacy
      services in Portuguese prisons. The information collected could be very useful to
      improve the Portuguese prison pharmacy services provided to prisoners.

PMID- 25763455
TI  - Assessing post-traumatic stress symptoms in a Latino prison population.
AB  - PURPOSE: The purpose of this paper is to assess the reliability and validity of
      the Spanish version of the Davidson trauma scale (DTS-S) and to determine the
      prevalence and correlates of post-traumatic stress disorder (PTSD) symptoms in a
      non-clinical random sample of prison inmates. DESIGN/METHODOLOGY/APPROACH:
      Probabilistic samples of 1,179 inmates from 26 penal institutions in Puerto Rico
      were selected using a multistage sampling design. Population estimates and
      correlations were obtained for PTSD, generalized anxiety and depression. The
      reliability, factor structure, and convergent validity of the DTS-S were
      assessed. Cross-validation was employed to confirm the results of the factor
      analyses. FINDINGS: Using the cut-offs adopted by the scale's author, 136 (13.4
      percent) of the inmates are likely to have current PTSD and 117 (11.6 percent)
      reach the cut-off for sub-threshold PTSD. Confirmatory factor analysis generated
      two factors explaining 53 percent of the variance. High reliabilities were
      obtained for the total scale (alpha=0.95) and for the frequency and severity
      scales (alpha=0.90 and 0.91). Significantly higher DTS-S scores were found for
      females (t=2.26, p<0.025), for inmates diagnosed with depression or anxiety
      (t=2.02, p<0.05), and those reporting suicide attempts (t=4.47, p<0.0001).
      ORIGINALITY/VALUE: Findings support that the DTS-S is a reliable and valid
      measure to assess PTSD symptoms in Latino inmate populations and to identify
      individuals at risk for the disorder that require confirmatory diagnosis and
      clinical interventions.

PMID- 25763456
TI  - Prison, a missing target to address issues related to drug detoxification and
      rehabilitation: Nepalese experiences.
AB  - PURPOSE: Drug use has numerous consequences on health, the economy, culture and
      the peace and security of families and communities. Drug users often engage in
      various criminal activities, including drug dealing, to sustain their drug use.
      Under Nepalese law, consumption, possession and sale of drugs are illegal, which
      increases the risk of incarceration for drug users. DESIGN/METHODOLOGY/APPROACH:
      Using a phenomenological/qualitative approach, the paper explores how various
      activities can lead to the arrest of drug users, how they cope without taking
      drugs in custody and prison and how they plan abstinence after release. FINDINGS:
      Participants engaged in various categories of criminal activity, including
      stealing, looting, etc. Most of the drug users were in custody and prison at
      least once. Drug use relapses led the participants to re-engage in criminal
      activities including drug dealing. Parents were often overburdened by their sons
      and daughter's drug use and were worried about their repeated relapses. Finally,
      some parents negotiated with their sons and daughters to keep them in prison
      where they would be able to stay without taking drugs and their involvement in
      crimes and conflicts would decrease. ORIGINALITY/VALUE: Keeping substance abusers
      in prison does not appear to be an effective strategy, as many participants
      relapse after release from prison. However, a prison-based educational and health
      promotion strategy would be beneficial for drug users to develop knowledge and
      skills on staying drug-free. However, to date, no effort has been made to provide
      such services to drug users and develop their coping strategy after release.

PMID- 25763457
TI  - A Constrained Helical Peptide Against S100A4 Inhibits Cell Motility in Tumor
      Cells.
AB  - S100A4, a member of a calcium-regulated protein family, is involved in various
      cellular signaling pathways. From many studies over the last decade or so, it has
      become clear that it is involved in tumor metastasis, probably playing a
      determinative role. However, except the phenothiazine group of drugs, no
      significant inhibitor of S100A4 has been reported. Even the phenothiazines are
      very weak inhibitors of S100A4 action. In this study, we report design and
      development of a conformationally constrained helical peptide modeled on the non
      muscle myosin peptide that binds to S100A4. This conformationally constrained
      peptide binds to S100A4 with a dissociation constant in the nanomolar range. We
      also synthesized a peptide for experimental control that bears several alanine
      mutations in the peptide-protein interface. We demonstrate that the former
      peptide specifically inhibits motility of H1299 and MCF-7 cells in a wound
      healing assay. Structures of several S100A4-ligand complexes suggest that it may
      be possible to develop a smaller peptide-small molecule conjugate having high
      affinity for S100A4. Peptide-drug conjugates of this kind may play an important
      role in developing drug leads against this antimetastasis target. 

PMID- 25763459
TI  - Cholangitis 3 years after laparoscopic cholecystectomy.

PMID- 25763458
TI  - Risk Assessment of Tuberculosis in Contacts by IFN-gamma Release Assays. A
      Tuberculosis Network European Trials Group Study.
AB  - RATIONALE: Latent infection with Mycobacterium tuberculosis is defined by a
      positive IFN-gamma release assay (IGRA) result in the absence of active
      tuberculosis. Only few, mostly monocentric studies have evaluated the role of
      IGRAs to predict the development of tuberculosis in recent contacts in low
      incidence countries of tuberculosis. OBJECTIVES: To analyze IGRA results and the
      effect of preventive chemotherapy on tuberculosis progression rates among recent
      contacts. METHODS: Results from contact investigations at 26 centers in 10
      European countries including testing for latent infection with M. tuberculosis by
      the QuantiFERON-TB Gold In-Tube (QFT) test or the T-SPOT.TB (TSPOT) were
      prospectively collected and analyzed. MEASUREMENTS AND MAIN RESULTS: Among 5,020
      contacts of 1,023 index cases, 25 prevalent secondary cases were identified at
      screening. Twenty-four incident cases occurred among 4,513 contacts during 12,326
      years of cumulative follow-up. In those with a positive IGRA result, tuberculosis
      incidence was 0.2 (QFT) and 0 (TSPOT) per 100 patient-years when contacts
      received preventive chemotherapy versus 1.2 (QFT) and 0.8 (TSPOT) per 100 patient
      years in those not treated (38 and 37 patients needed to be treated to prevent
      one case, respectively). Positive and negative predictive values were 1.9% (95%
      confidence interval [CI], 1.1-3.0) and 99.9% (95% CI, 99.7-100) for the QFT and
      0.7% (95% CI, 0.1-2.6) and 99.7% (95% CI, 99.1-99.9) for the TSPOT. CONCLUSIONS:
      Tuberculosis rarely developed among contacts, and preventive chemotherapy
      effectively reduced the tuberculosis risk among IGRA-positive contacts. Although
      the negative predictive value of IGRAs is high, the risk for the development of
      tuberculosis is poorly predicted by these assays.

PMID- 25763460
TI  - The Pregnancy Manifesto: Notes on How to Extract Reproduction from the Petri
      Dish.
AB  - This article draws on 200 stories of procreation in an effort to revise a key
      narrative about how humans come into being in technological societies. Before
      assigning Emily Martin's famous article "the egg and the sperm," I asked Israeli
      undergraduates to explain to a beloved girl how children come into the world.
      Their narratives included detailed accounts of sperm-ovum encounters as if
      envisioned through a microscope; the process of pregnancy was missing from most
      of the stories. My analysis illuminates the local politics of technologized
      reproduction underlying the invisibility of women's procreative labor and
      suggests an alternative story of procreation as hard work done by women's bodies
      within somatic and social environments. The discussion points beyond students'
      narratives, at the reluctance of anthropologists of reproduction to take up
      pregnancy as a unit of social analysis. With the emergence of the new genomic
      sciences, studies of the political ecology of procreative labor become urgent. 

PMID- 25763462
TI  - New ruthenium bis(terpyridine) methanofullerene and pyrrolidinofullerene
      complexes: synthesis and electrochemical and photophysical properties.
AB  - A series of terpyridine (tpy) methanofullerene and pyrrolidinofullerene dyads
      linked via p-phenylene or p-phenyleneethynylenephenylene (PEP) units is
      presented. The coordination to ruthenium(II) yields donor-bridge-acceptor
      assemblies with different lengths. Cyclic voltammetry and UV-vis and luminescence
      spectroscopy are applied to study the electronic interactions between the active
      moieties. It is shown that, upon light excitation of the ruthenium(II)-based
      (1)MLCT transition, the formed (3)MLCT state is readily quenched in the presence
      of C60. The photoinduced dynamics have been studied by transient absorption
      spectroscopy, which reveals fast depopulation of the (3)MLCT (73-406 ps). As a
      consequence, energy transfer occurs, populating a long-lived triplet state, which
      could be assigned to the (3)C60* state. 

PMID- 25763461
TI  - Observing lysozyme's closing and opening motions by high-resolution single
      molecule enzymology.
AB  - Single-molecule techniques can monitor the kinetics of transitions between enzyme
      open and closed conformations, but such methods usually lack the resolution to
      observe the underlying transition pathway or intermediate conformational
      dynamics. We have used a 1 MHz bandwidth carbon nanotube transistor to
      electronically monitor single molecules of the enzyme T4 lysozyme as it processes
      substrate. An experimental resolution of 2 MUs allowed the direct recording of
      lysozyme's opening and closing transitions. Unexpectedly, both motions required
      37 MUs, on average. The distribution of transition durations was also independent
      of the enzyme's state: either catalytic or nonproductive. The observation of
      smooth, continuous transitions suggests a concerted mechanism for glycoside
      hydrolysis with lysozyme's two domains closing upon the polysaccharide substrate
      in its active site. We distinguish these smooth motions from a nonconcerted
      mechanism, observed in approximately 10% of lysozyme openings and closings, in
      which the enzyme pauses for an additional 40-140 MUs in an intermediate,
      partially closed conformation. During intermediate forming events, the number of
      rate-limiting steps observed increases to four, consistent with four steps
      required in the stepwise, arrow-pushing mechanism. The formation of such
      intermediate conformations was again independent of the enzyme's state. Taken
      together, the results suggest lysozyme operates as a Brownian motor. In this
      model, the enzyme traces a single pathway for closing and the reverse pathway for
      enzyme opening, regardless of its instantaneous catalytic productivity. The
      observed symmetry in enzyme opening and closing thus suggests that substrate
      translocation occurs while the enzyme is closed. 

PMID- 25763463
TI  - Stability of the acrysof toric intraocular lens in combined cataract surgery and
      transconjunctival sutureless vitrectomy.
AB  - PURPOSE: To report the outcomes of combined cataract surgery with toric
      intraocular lens (IOL) implantation when performed in conjunction with
      transconjunctival sutureless pars plana vitrectomy. DESIGN: Retrospective
      interventional case series. PARTICIPANTS: Consecutive series of 55 eyes of 51
      patients from April 2007 to December of 2010. METHODS: All eyes underwent
      combined simultaneous small incision cataract surgery, toric IOL implantation,
      and transconjunctival sutureless vitrectomy surgery. MAIN OUTCOME MEASURES:
      Postoperative visual acuity, postoperative astigmatism, and rotational stability
      of the IOL. RESULTS: Preoperative best-corrected visual acuity was 0.32 +/- 0.15
      logMar (Snellen 20/43) and improved to 0.16 +/- 0.10 (Snellen 20/29)
      postoperatively uncorrected (P < 0.01) and to 0.08 +/- 0.11 best-corrected
      (Snellen 20/24) (P < 0.01). Preoperative astigmatism was 1.75 +/- 1.0 diopters
      (D) (range, 0-4.75 D) and improved to 0.5 +/- 0.50 D (range, 0-2.5 D)
      postoperatively (P < 0.01). Final measured postoperative IOL axis deviation from
      target axis was 4 +/- 6 degrees  (range, 0-32). Final IOL axis was within 5
      degrees  of target in 47 (85%) eyes, within 10 degrees of target in 51 (93%)
      eyes, and was within 15 degrees  of target in 52 (95%) eyes. CONCLUSION: Toric
      lens position and axis remained stable after implantation during combined
      cataract surgery and transconjunctival sutureless vitrectomy.

PMID- 25763464
TI  - Pneumatic retinopexy for primary repair of rhegmatogenous retinal detachments.
AB  - PURPOSE: To evaluate anatomical and functional outcomes of pneumatic retinopexy
      (PR) for primary repair of rhegmatogenous retinal detachments and to determine
      demographic and ocular risk factors for failure of the procedure. DESIGN:
      Retrospective interventional case series. METHODS: A chart review on 97 eyes of
      97 consecutive patients who had undergone PR as the initial procedure for
      unilateral recent primary retinal detachments with causative break(s) in the
      superior two-third of the retina. After injection of 0.35 mL to 0.60 mL of sulfur
      hexafluoride, 6 hours face-down positioning, and the steamroller maneuver, the
      patient's head position was changed so that the gas could efficiently tamponade
      the retinal break(s). Pre- and post-gas injection laser photocoagulation of
      break(s) and 360 degrees  peripheral retina was applied. RESULTS: Seventy-two
      male and 25 female patients were included in this study. The single-operation
      success rate was 82.5%. The pars plana vitrectomy procedure as the second
      intervention was not adversely affected by the preceding PR. Presence of
      proliferative vitreoretinopathy (odds ratio: 58.7, 95% confidence interval: 7.8
      443.5) and delay between initial symptoms and PR (odds ratio: 1.21 per each
      additional day, 95% confidence interval: 1.07-1.37) were the only independent
      predictors for the failure. CONCLUSION: With proper selection of cases, PR is a
      good surgical option for primary rhegmatogenous retinal detachments with
      acceptable success rate, minimal discomfort to the patient, and minimal surgical
      risks.

PMID- 25763465
TI  - New self-retaining sutureless cellulose flanged disposable contact viewing system
      for vitreoretinal surgery.

PMID- 25763466
TI  - Suspected community-acquired pneumonia in an ambulatory setting (CAPA): a French
      prospective observational cohort study in general practice.
AB  - BACKGROUND: Few studies have addressed the pragmatic management of ambulatory
      patients with suspected community-acquired pneumonia (CAP) using a precise
      description of the disease with or without chest X-ray (X-ray) evidence. AIMS: To
      describe the characteristics, clinical findings, additional investigations and
      disease progression in patients with suspected CAP managed by French General
      Practitioners (GPs). METHODS: The patients included were older than 18 years,
      with signs or symptoms suggestive of CAP associated with recent-onset unilateral
      crackles on auscultation or a new opacity on X-ray. They were followed for up to
      6 weeks. Descriptive analyses of all patients and according to their management
      with X-rays were carried out. RESULTS: From September 2011 to July 2012, 886
      patients have been consulted by 267 GPs. Among them, 278 (31%) were older than 65
      years and 337 (38%) were at increased risk for invasive pneumococcal disease. At
      presentation, the three most common symptoms, cough (94%), fever (93%), and
      weakness or myalgia (81%), were all observed in 70% of patients. Unilateral
      crackles were observed in 77% of patients. Among patients with positive
      radiography (64%), 36% had no unilateral crackles. A null CRB-65 score was
      obtained in 62% of patients. Most patients (94%) initially received antibiotics
      and experienced uncomplicated disease progression regardless of their management
      with X-rays. Finally, 7% of patients were hospitalised and 0.3% died.
      CONCLUSIONS: Most patients consulting GPs for suspected CAP had the three
      following most common symptoms: cough, fever, and weakness or myalgia. More than
      a third of them were at increased risk for invasive pneumococcal disease. With or
      without X-rays, most patients received antibiotics and experienced uncomplicated
      disease progression.

PMID- 25763467
TI  - Oregano Essential Oil as an Antimicrobial and Antioxidant Additive in Food
      Products.
AB  - Food consumers and industries urged the need of natural alternatives to assure
      food safety and quality. As a response, the use of natural compounds from herbs
      and spices is an alternative to synthetic additives associated with toxic
      problems. This review discusses the antimicrobial and antioxidant activity of
      oregano essential oil (OEO) and its potential as a food additive. Oregano is a
      plant that has been used as a food seasoning since ancient times. The common name
      of oregano is given to several species: Origanum (family: Lamiaceae) and Lippia
      (family: Verbenaceae), amongst others. The main compounds identified in the
      different OEOs are carvacrol and thymol, which are responsible for the
      characteristic odor, antimicrobial, and antioxidant activity; however, their
      content may vary according to the species, harvesting season, and geographical
      sources. These substances as antibacterial agents make the cell membrane
      permeable due to its impregnation in the hydrophobic domains, this effect is
      higher against gram positive bacteria. In addition, the OEO has antioxidant
      properties effective in retarding the process of lipid peroxidation in fatty
      foods, and scavenging free radicals. In this perspective, the present review
      analyzes and discusses the state of the art about the actual and potential uses
      of OEO as an antimicrobial and antioxidant food additives. 

PMID- 25763468
TI  - Functional divergence of heme-thiolate proteins: a classification based on
      spectroscopic attributes.

PMID- 25763469
TI  - Pinosylvin and monomethylpinosylvin, constituents of an extract from the knot of
      Pinus sylvestris, reduce inflammatory gene expression and inflammatory responses
      in vivo.
AB  - Scots pine (Pinus sylvestris) is known to be rich in phenolic compounds, which
      may have anti-inflammatory properties. The present study investigated the anti
      inflammatory effects of a knot extract from P. sylvestris and two stilbenes,
      pinosylvin and monomethylpinosylvin, isolated from the extract. Inflammation is
      characterized by increased release of pro-inflammatory and regulatory mediators
      including nitric oxide (NO) produced by the inducible nitric oxide synthase
      (iNOS) pathway. The knot extract (EC50 values of 3 and 3 MUg/mL) as well as two
      of its constituents, pinosylvin (EC50 values of 13 and 15 MUM) and
      monomethylpinosylvin (EC50 values of 8 and 12 MUM), reduced NO production and
      iNOS expression in activated macrophages. They also inhibited the production of
      inflammatory cytokines IL-6 and MCP-1. More importantly, pinosylvin and
      monomethylpinosylvin exerted a clear anti-inflammatory effect (80% inhibition at
      the dose of 100 mg/kg) in the standard in vivo model, carrageenan-induced paw
      inflammation in the mouse, with the effect being comparable to that of a known
      iNOS inhibitor L-NIL. The results reveal that the Scots pine stilbenes pinosylvin
      and monomethylpinosylvin are potential anti-inflammatory compounds. 

PMID- 25763470
TI  - TBAI-catalyzed oxidative cross-coupling of phenols and 2-aminoacetophenones.
AB  - An iodide-catalyzed oxidative cross-coupling between phenols and 2
      aminoacetophenones has been developed. Using catalytic amounts of
      tetrabutylammoniumiodide (TBAI) as an iodine-containing catalyst and aqueous
      solutions of tert-butyl hydro-peroxide (TBHP) as the stoichiometric co-oxidant, a
      variety of alpha-phenoxylated 2-aminoacetophenones could be obtained in yields of
      up to 92% after remarkably short reaction times (20 min). This is a very rare
      example for an iodide-catalyzed intermolecular cross-coupling utilizing phenols.
      However, this efficient methodology could be further extended toward an
      intramolecular variant which gives direct access to a range of dihydro-4H
      benzo[e][1,3]oxazin-4-ones. 

PMID- 25763471
TI  - Improving family history collection.
AB  - Family history is important for assessing risk of cancer. This study aimed to
      improve cancer family history communication and collection by training and
      motivating lay individuals to construct pedigrees. The authors' ultimate goal is
      to improve identification of familial cancer. Participants (n = 200) completed
      preintervention, postintervention, and 1-week follow-up surveys to assess
      pedigree construction. The intervention reviewed basic construction and
      interpretation of a pedigree for familial cancer. As a result of intervention,
      individuals reported more positive attitudes about collecting family history,
      were more likely to intend to speak to family and physicians about cancer risk,
      better understood a sample pedigree, and constructed more detailed pedigrees of
      their family history. At follow-up, 25% of the sample had spoken with their
      families about cancer risk. For those individuals who had not spoken with family,
      higher postintervention pedigree knowledge was associated with greater intentions
      to speak with family in the future. The intervention improved the communication
      and collection of pedigrees and communication about cancer risk, which could be
      used to improve the identification of individuals with familial cancers and
      awareness of family cancer risk. 

PMID- 25763472
TI  - Interaction of platelets with endothelial progenitor cells in the experimental
      atherosclerosis: Role of transplanted endothelial progenitor cells and platelet
      microparticles.
AB  - BACKGROUND INFORMATION: Recent studies suggest that endothelial progenitor cells
      (EPCs) and platelets have an important role in repair following vascular injury.
      Although evidence suggest that platelets are essential in EPC attracting, homing
      and differentiation to the injury site; however, the platelet effects on EPC
      function in atherosclerosis have received less attention. In this context, we
      followed the consequences of circulating EPCs and platelet microparticles (PMPs)
      administration on platelet-EPC interaction in atherosclerosis and the involved
      mechanisms. The experiments were performed on Golden Syrian hamsters divided in
      five equal groups: control (C), hypertensive-hypercholesterolemic (HH), HH
      treated with EPCs (HH-EPCs) or PMPs (HH-PMPs) and HH treated with EPCs and PMPs
      (HH-EPCs-PMPs). RESULTS: Compared with C group, EPCs isolated from HH and HH-PMPs
      groups presented a reduction of endothelial nitric oxide synthase and vascular
      endothelial growth factor expressions and an increase in thrombospondin-1
      expression and inflammatory molecule secretion: interleukin 8 (IL)-8,
      myeloperoxidase (MPO) and plasminogen activator inhibitor-1 (PAI-1). EPC
      administration had beneficial effects, the obtained results being similar with
      those from the C group, while the combination with PMPs did not improve the EPC
      influences. Static coincubation of EPCs from HH and HH-PMPs with analogous
      platelets resulted in an increased EPC adhesion/migration, and IL-8, monocyte
      chemotactic protein-1, regulated on activation, normal T expressed and secreted,
      MPO and PAI-1 release, explained by the platelet hyperaggregability induced by
      pronounced distribution of vasodilator-stimulated phosphoprotein and filamentous
      actin, and the secretion of proinflammatory factors: IL-1beta, -6, -8, CD40
      ligand. EPC therapy alone revealed an impaired platelet-EPC interaction directly
      correlated with the reduction of inflammatory markers and platelet aggregability.
      Moreover, in a dynamic flow system, EPCs and platelets from HH and HH-PMPs
      exhibited weakened interplay abilities, while EPC transplantation reinforces
      them. CONCLUSIONS: The present study demonstrates that HH animals revealed
      functional impairment of EPCs and platelets, which correlate with their reduced
      contribution to re-endothelialisation at the injury site, although in vitro
      exposure to immobilised platelets promotes their adhesion and migration. EPC
      administration alone recovers EPC/platelet functions and consolidates their
      interaction under dynamic flow conditions. These findings disclose new advances
      in understanding the platelet-EPC interaction and its role in the vascular
      repair.

PMID- 25763474
TI  - 25(th) Anniversary state-of-the-art expert discussion With Mark L. Wulkan, MD, on
      the evolution of pediatric obesity surgery.

PMID- 25763473
TI  - The Discovery of Orally Bioavailable Tyrosine Threonine Kinase (TTK) Inhibitors:
      3-(4-(heterocyclyl)phenyl)-1H-indazole-5-carboxamides as Anticancer Agents.
AB  - The acetamido and carboxamido substituted 3-(1H-indazol-3-yl)benzenesulfonamides
      are potent TTK inhibitors. However, they display modest ability to attenuate
      cancer cell growth; their physicochemical properties, and attendant
      pharmacokinetic parameters, are not drug-like. By eliminating the polar 3
      sulfonamide group and grafting a heterocycle at the 4 position of the phenyl
      ring, potent inhibitors with oral exposure were obtained. An X-ray cocrystal
      structure and a refined binding model allowed for a structure guided approach.
      Systematic optimization resulted in novel TTK inhibitors, namely 3-(4
      (heterocyclyl)phenyl)-1H-indazole-5-carboxamides. Compounds incorporating the 3
      hydroxy-8-azabicyclo[3.2.1]octan-8-yl bicyclic system were potent (TTK IC50 < 10
      nM, HCT116 GI50 < 0.1 MUM), displayed low off-target activity (>500*), and
      microsomal stability (T(1/2) > 30 min). A subset was tested in rodent PK and
      mouse xenograft models of human cancer. Compound 75 (CFI-401870) recapitulated
      the phenotype of TTK RNAi, demonstrated in vivo tumor growth inhibition upon oral
      dosing, and was selected for preclinical evaluation.

PMID- 25763475
TI  - Robot-assisted versus laparoscopic adrenalectomy: a systematic review and meta
      analysis.
AB  - BACKGROUND: More recently, robot-assisted adrenalectomy (RA) has emerged as an
      attractive alternative to laparoscopic adrenalectomy (LA), and many studies have
      shown the feasibility and safety of RA. However, the short- and long-term
      outcomes of RA versus LA have not been adequately assessed, and the advantage
      over the laparoscopic approach has not been demonstrated. The aim of this study
      was to compare the outcomes of RA versus LA by means of a systematic review and
      meta-analysis of the available literature in the early experience. MATERIALS AND
      METHODS: A systematic search of PubMed, SCI/SSCI, CNKI, and the Cochrane Library
      was performed to identify prospective randomized controlled trials and
      retrospective observational studies that compared RA and LA and were published
      between January 2006 to the end of December 2012. Outcomes of interest included
      demographic and clinical characteristics, perioperative variables, and
      complications. The meta-analysis was prepared in accordance with the Quality of
      Reporting of Meta-analyses (QUOROM) statement. RESULTS: Eight trials (232 cases
      and 297 controls) assessing RA versus LA were considered suitable for meta
      analysis, including six prospective and two retrospective studies. There was a
      significant trend to choose patients for the performance of RA who were
      associated with a lower body mass index (weighted mean difference [WMD]=-2.78
      kg/m(2); 95% confidence interval [CI], -3.00 to -2.55; P<.001) and higher
      incidence of previous surgery (odds ratio=1.59; 95% CI, 0.99-2.54; P=.05). There
      were no significant differences between the two groups in any other of the
      demographic parameters. With regard to perioperative variables, although there
      was a significant difference in the operating time in favor of LA (WMD=17.52
      minutes; 95% CI, 3.48-31.56; P=.01), patients having RA might benefit from
      significantly less blood loss (WMD=-19.00 mL; 95% CI, -34.58 to -3.41; P=.02) and
      shorter length of hospital stay (WMD=-0.35 day; 95% CI, -0.51 to -0.19; P<.001).
      There were no significant differences between RA and LA with regard to conversion
      rates and overall complications. Sensitivity analysis performed by two methods
      both showed a positive reversal in the operating time with the statistical
      significance removed compared with the original analysis. CONCLUSIONS: In the
      early experience, our data suggest that RA, compared with LA, may be a safe and
      feasible option associated with less blood loss and shorter hospital stay when
      performed by experienced surgeons in selected patients.

PMID- 25763476
TI  - Transfer of chirality in the rhodium-catalyzed intramolecular formal hetero-[5 +
      2] cycloaddition of vinyl aziridines and alkynes: stereoselective synthesis of
      fused azepine derivatives.
AB  - By taking advantage of vinyl aziridines as a heteroatom-containing five-atom
      component in rhodium-catalyzed intramolecular formal hetero-[5 + 2] cycloaddition
      reactions with alkynes, a highly efficient method for the synthesis of fused
      azepine derivatives at 30  degrees C was developed. The reaction has broad
      substrate scope and tolerates a wide range of functional groups. The chirality of
      vinyl aziridine-alkyne substrates can be completely transferred to the
      cycloadducts, representing an atom-economic and enantiospecific protocol for the
      construction of fused 2,5-dihydroazepines for the first time. 

PMID- 25763477
TI  - Early vs late tracheostomy in critically ill patients: a systematic review and
      meta-analysis.
AB  - BACKGROUND AND AIMS: This study aims to compare the outcomes of early
      tracheostomy (ET) (<=10 days after translaryngeal intubation) with late
      tracheostomy (LT) (>10 days after translaryngeal intubation) in critically ill
      patients with prolonged mechanical ventilation (MV). METHODS: We searched PubMed,
      EMBASE and the Cochrane Library from inception to April 2014. We included all
      randomized controlled trials (RCTs), which compared ET with LT in critically ill
      patients. There was no language restriction. Two authors extracted data and
      conducted a quality assessment. Meta-analyses using the fixed-effects or random
      effects model were conducted for mortality, incidence of ventilator-associated
      pneumonia (VAP), duration of MV and sedation, length of intensive care unit (ICU)
      stay. RESULTS: We enrolled 9 studies, in which a total of 2040 patients were
      randomized to either ET group (N = 1018) or LT group (N = 1022). ET might reduce
      the duration of sedation [weighted mean difference (WMD) = -5.99 days; 95%
      confidence intervals (CI) = -11.41 to -0.57 days; P = 0.03]. ET did not
      significantly alter the mortality [relative risk (RR) = 0.88; 95% CI = 0.76-1.00;
      P = 0.06], incidence of VAP (RR = 0.84; 95% CI = 0.66-1.08; P = 0.17), duration
      of MV (WMD = -4.46 days; 95% CI = -12.61 to 3.69 days; P = 0.28) and length of
      ICU stay (WMD = -7.57 days; 95% CI = -15.42 to 0.29 days; P = 0.06). CONCLUSIONS:
      Our meta-analysis suggested that ET might be able to reduce the duration of
      sedation but did not significantly alter the mortality, incidence of VAP,
      duration of MV and length of ICU stay.

PMID- 25763478
TI  - Mechanical properties and polymerization shrinkage of composite resins light
      cured using two different lasers.
AB  - OBJECTIVE: The purpose of the present study was to investigate the usefulness of
      457 and 473 nm lasers for the curing of composite resins during the restoration
      of damaged tooth cavity. BACKGROUND DATA: Monochromaticity and coherence are
      attractive features of laser compared with most other light sources. Better
      polymerization of composite resins can be expected. MATERIALS AND METHODS: Eight
      composite resins were light cured using these two lasers and a light-emitting
      diode (LED) light-curing unit (LCU). To evaluate the degrees of polymerization
      achieved, polymerization shrinkage and flexural and compressive properties were
      measured and compared. RESULTS: Polymerization shrinkage values by 457 and 473 nm
      laser, and LED ranged from 10.9 to 26.8, from 13.2 to 26.1, and from 11.5 to 26.3
      MUm, respectively. The values by 457 nm laser was significantly different from
      those by 473 and LED LCU (p<0.05). However, there was no statistical difference
      between values by 473 and LED LCU. Before immersion in distilled water, flexural
      strength (FS) and compressive modulus (CM) of the specimens were inconsistently
      influenced by LCUs. On the other hand, flexural modulus (FM) and compressive
      strength (CS) were not significantly different for the three LCUs (p>0.05). For
      the tested LCUs, no specific LCU could consistently achieve highest strength and
      modulus from the specimens tested. CONCLUSIONS: Two lasers (457 and 473 nm) can
      polymerize composite resins to the level that LED LCU can achieve despite
      inconsistent trends of polymerization shrinkage and flexural and compressive
      properties of the tested specimens.

PMID- 25763479
TI  - Differential isotopic enrichment to facilitate characterization of asymmetric
      multimeric proteins using hydrogen/deuterium exchange mass spectrometry.
AB  - Hydrogen/deuterium exchange (HDX) coupled to mass spectrometry has emerged as a
      powerful tool for analyzing the conformational dynamics of protein-ligand and
      protein-protein interactions. Recent advances in instrumentation and methodology
      have expanded the utility of HDX for the analysis of large and complex proteins;
      however, asymmetric dimers with shared amino acid sequence present a unique
      challenge for HDX because assignment of peptides with identical sequence to their
      subunit of origin remains ambiguous. Here we report the use of differential
      isotopic labeling to facilitate HDX analysis of multimers using HIV-1 reverse
      transcriptase (RT) as a model. RT is an asymmetric heterodimer of 51 kDa (p51)
      and 66 kDa (p66) subunits. The first 440 residues of p51 and p66 are identical.
      In this study differentially labeled RT was reconstituted from isotopically
      enriched ((15)N-labeled) p51 and unlabeled p66. To enable detection of (15)N
      deuterated RT peptides, the software HDX Workbench was modified to follow a 100%
      (15)N model. Our results demonstrated that (15)N enrichment of p51 did not affect
      its conformational dynamics compared to unlabeled p51, but (15)N-labeled p51 did
      show different conformational dynamics than p66 in the RT heterodimer.
      Differential HDX-MS of isotopically labeled RT in the presence of the non
      nucleoside reverse transcriptase inhibitor (NNRTI) efavirenz (EFV) showed subunit
      specific perturbation in the rate of HDX consistent with previously published
      results and the RT-EFV cocrystal structure. 

PMID- 25763480
TI  - Emerging features of ER resident J-proteins in plants.
AB  - J-proteins are co-chaperone components of the HSP70 system. J-proteins stimulate
      Hsp70ATPase activity, which is responsible for stabilizing the interaction of
      Hsp70 with client proteins. J-proteins are localized in various intracellular
      compartments including the cytoplasm, mitochondria and endoplasmic reticulum
      (ER). Five types of ER resident J-proteins (ERdjs) have been found in plants
      (P58, ERdj2, ERdj2A, ERdj3B and ERdj7). Rice OsERdj3A is located in the vacuole
      and protein storage vacuoles (PSV, PB-II) under conditions of ER stress. J
      proteins that are localized to the vacuole or lysosome are not found in mammals
      and yeast, suggesting that the presence of OsERdj3A in the vacuole is plant
      specific and one of the features unique to plant ERdjs. In this review, we
      summarize the current state of knowledge and recent research advancements
      regarding plant ERdjs, and compare mammalian and yeast ERdjs with plant ERdjs. 

PMID- 25763481
TI  - Contribution of ABA UDP-glucosyltransferases in coordination of ABA biosynthesis
      and catabolism for ABA homeostasis.
AB  - The phytohormone abscisic acid (ABA) plays a crucial role in numerous aspects of
      plant growth and environmental stress responses. Endogenous ABA levels are
      regulated by a balance between its biosynthetic and catabolic activities. This
      balance may occur at multiple levels and includes the expression of genes
      involved in these processes. ABA UDP-glucosyltransferase (UGT), the major player
      in the ABA conjugation pathway, has been shown to have a marginal effect on free
      ABA levels. However, recent studies provide new insight into the importance of
      the ABA conjugation pathway in contributing to the control of ABA homeostasis.
      Gain-of-function and loss-of-function mutant analyses have revealed that UGT71B6,
      an ABA UGT, and its 2 closely related homologs, UGT71B7 and UGT71B8, play a
      crucial role in ABA homeostasis and in adaptation to various abiotic stresses. 

PMID- 25763482
TI  - The glucan phosphorylation mediated by alpha-glucan, water dikinase (GWD) is also
      essential in the light phase for a functional transitory starch turn-over.
AB  - Starch phosphorylation mediated by the alpha-glucan, water dikinase (GWD) is
      crucial for transitory starch metabolism. The impact of the GWD action on
      transitory starch metabolism was analyzed in Arabidopsis mutants either lacking
      or revealing different reduced levels of GWD activity. In these mutants, glucose
      6-phosphate (G6P) levels of the transitory leaf starch, the average leaf starch
      content, as well as alterations in the growth phenotype were determined under
      different light length conditions, including continuous light. Based on
      biochemical and growth phenotypical data, we found that the length of the light
      phase affects the phosphorylation state of the transitory starch and, by this,
      the average leaf starch content and the resulting growth of the plants.
      Additionally, we discuss data referring to an involvement of the GWD mediated
      glucan phosphorylation in starch synthesis, as, e.g., starch phosphorylation
      occurred even when a dark phase was omitted. 

PMID- 25763483
TI  - Lysine catabolism, amino acid transport, and systemic acquired resistance: what
      is the link?.
AB  - Lysine is an essential amino acid for human nutrition, which is generally low in
      cereal diets. Its biosynthesis via the aspartate-pathway and catabolism is
      controlled by complex feedback mechanisms. Recently, aspartate-derived amino
      acids were found to be elevated during pathogen infection in Arabidopsis and a
      lysine catabolite, pipecolic acid, was identified as critical regulator of
      systemic acquired resistance. Pipecolic acid is mobile in plants, functions as an
      intensifier of defense responses and mediates systemic acquired resistance
      establishment via signal amplification. The altered pathogen defense in several
      mutants with altered homeostasis of aspartate-derived amino acids, such as
      lysine, had already provided a genetic link with amino acid homeostasis.
      Furthermore, the modification of amino acid transport and distribution within
      tissues not only affected the plant growth performance, but also the plant
      pathogen interaction. The ectopic overexpression of a gene encoding a high
      affinity importer with preference to basic amino acids, such as lysine, cationic
      amino acid transporter1 (CAT1), improved the disease resistance to a
      hemibiotrophic bacterial pathogen in Arabidopsis via a constitutively activated
      salicylic acid pathway. The importance of Asp-derived amino acid homeostasis for
      plant systemic acquired resistance and on overall plant growth performance may be
      relevant to resistance and nutritional quality breeding. Whether nitrogen
      fertilization has an impact on crop pest control management via amino acid
      homeostasis is briefly discussed.

PMID- 25763484
TI  - Resistance of callose synthase activity to free fatty acid inhibition as an
      indicator of Fusarium head blight resistance in wheat.
AB  - The fungal pathogen Fusarium graminearum is the causal agent of Fusarium head
      blight (FHB); a devastating crop disease resulting in heavy yield losses and
      grain contamination with mycotoxins. We recently showed that the secreted lipase
      FGL1, a virulence factor of F. graminearum, targets plant defense-related callose
      biosynthesis during wheat head infection. This effector-like function is based on
      a FGL1-mediated release of polyunsaturated free fatty acids (FFA) that can
      inhibit callose synthase activity. The importance of FGL1 in successful wheat
      head colonization was demonstrated in FGL1 disruption mutants (Deltafgl1), where
      infection was restricted to directly inoculated spikelets and accompanied by
      strong callose deposition in the spikelet's phloem. The application of
      polyunsaturated FFA to Deltafgl1-infected spikelets prevented callose deposition
      in the phloem and partially restored wheat head colonization.   The comparative
      analysis of 3 wheat cultivars revealed that the level of resistance to FHB
      correlated with resistance to FFA-dependent inhibition of callose biosynthesis.
      Therefore, resistance of callose biosynthesis to FFA inhibition might be used as
      marker and/or direct target in the breeding of FHB-resistant wheat cultivars. 

PMID- 25763485
TI  - Physiological response of rice (Oryza sativa L.) genotypes to elevated nitrogen
      applied under field conditions.
AB  - Field experiment was conducted at G.B.P.U.A.T. Pantnagar, Uttarakhand, India in
      rainy season of 2008 and 2009 to study the impacts of increased nitrogen doses on
      growth dynamics, biomass partitioning, chaffy grain and nitrogen use efficiency
      in 4 rice genotypes viz., Vasumati, Tulsi, Kasturi and Krishna Hamsa. Four doses
      (N(0), N(50), N(100) and N(200) kg N ha(-1)) of nitrogen in the form of urea were
      applied in 3 split. Increased trend in growth dynamics during active tillering
      and flowering stage, and biomass partitioning at the time of active tillering and
      flowering stage was observed with respect to nitrogen doses. Chaffy grain number
      and chaffy grain weight per 5 panicles was significantly increased with enhancing
      nitrogen doses and was highest for Vasumati. Nitrogen use efficiency (NUE) was
      increased up to N(100) kg N ha(-1) and it was declined with rising nitrogen doses
      (N(200) kg N ha(-1)). The highest values for NUE was achieved by rice genotype
      Krishna Hamsa whereas lowest by Vasumati. In addition to this, a significant
      correlation between nitrogen doses and growth dynamics, biomass partitioning and
      chaffy grain was observed. These findings suggest that growth dynamics, biomass
      partitioning, chaffy grain could be enhanced by the input of high rate of
      nitrogen fertilizer but not nitrogen use efficiency. Therefore, this study is
      useful to screen most N efficient genotypes which can be strongly suggested to
      rice growers to enhance crop yield irrespective of use of high dose of N
      fertilizers.

PMID- 25763487
TI  - Memristors in the electrical network of Aloe vera L.
AB  - A memristor is a resistor with memory, which is a non-linear passive two-terminal
      electrical element relating magnetic flux linkage and electrical charge. Here we
      found that memristors exist in vivo. The electrostimulation of the Aloe vera by
      bipolar sinusoidal or triangle periodic waves induce electrical responses with
      fingerprints of memristors. Uncouplers carbonylcyanide-3-chlorophenylhydrazone
      and carbonylcyanide-4-trifluoromethoxy-phenyl hydrazone decrease the amplitude of
      electrical responses at low and high frequencies of bipolar periodic sinusoidal
      or triangle electrostimulating waves. Memristive behavior of an electrical
      network in the Aloe vera is linked to the properties of voltage gated ion
      channels: the K(+) channel blocker TEACl reduces the electric response to a
      conventional resistor. Our results demonstrate that a voltage gated K(+) channel
      in the excitable tissue of plants has properties of a memristor. The discovery of
      memristors in plants creates a new direction in the modeling and understanding of
      electrical phenomena in plants. 

PMID- 25763486
TI  - Environmental stress and flowering time: the photoperiodic connection.
AB  - Plants maximize their chances to survive adversities by reprogramming their
      development according to environmental conditions. Adaptive variations in the
      timing to flowering reflect the need for plants to set seeds under the most
      favorable conditions. A complex network of genetic pathways allows plants to
      detect and integrate external (e.g., photoperiod and temperature) and/or internal
      (e.g., age) information to initiate the floral transition. Furthermore different
      types of environmental stresses play an important role in the floral transition.
      The emerging picture is that stress conditions often affect flowering through
      modulation of the photoperiodic pathway. In this review we will discuss different
      modes of cross talk between stress signaling and photoperiodic flowering,
      highlighting the central role of the florigen genes in this process. 

PMID- 25763488
TI  - Lack of malate valve capacities lead to improved N-assimilation and growth in
      transgenic A. thaliana plants.
AB  - In this study we analyzed the relationship between malate valve capacities, N
      assimilation, and energy metabolism. We used transgenic plants either lacking the
      chloroplast NADP-dependent malate dehydrogenase or mutants with a decreased
      transcript level of the plastid-localized NAD-dependent malate dehydrogenase.
      Plants were grown on nitrate or ammonium, respectively, as the sole N-source and
      transcripts were analyzed by qRT-PCR. We could show that the lack of malate valve
      capacities enhances N-assimilation and plastidial glycolysis by increasing
      transcript levels of Fd-GOGATs or NADH-GOGAT and plastidic NAD-GAPDHs (GapCps),
      respectively. Based on our results, we conclude that the lack of malate valve
      capacities is balanced by an increase of the activity of plastid-localized
      glycolysis in order to cover the high demand for plastidial ATP, stressing the
      importance of the plastids for energy metabolism in plant cells. 

PMID- 25763489
TI  - AtHAP5A modulates freezing stress resistance in Arabidopsis independent of the
      CBF pathway.
AB  - The heme-associated proteins (HAPs, also known as nuclear factor y, subunit A/B/C
      (NF-YA/B/C)) have been reported to bind specifically to DNA fragments containing
      CCAAT-box, however, the physiological functions and direct targets of these HAP
      proteins remain unclear in plants. In our recent study, we found that AtHAP5A and
      AtXTH21 positively modulated freezing stress resistance, and chromatin
      immunoprecipitation (ChIP) assay and genetic evidence indicated that AtHAP5A
      might act in the upstream of AtXTH21 in freezing stress. Moreover, AtHAP5A and
      AtXTH21 had significant effects on inhibiting cold stress-induced reactive oxygen
      species (ROS) accumulation and activating ABA-related genes' expression. Thus, a
      possible model that depicting AtHAP5A-mediated cold stress responses was proposed
      in this study, and we highlighted that AtHAP5A modulates freezing stress
      resistance in Arabidopsis through binding to CCAAT motif of AtXTH21, which is
      independent of the CBF pathway.

PMID- 25763490
TI  - HAESA and HAESA-LIKE2 activate organ abscission downstream of NEVERSHED and
      EVERSHED in Arabidopsis flowers.
AB  - A ligand-receptor module comprised of the peptide inflorescence deficient in
      abscission (IDA) and the receptor-like kinases HAESA (HAE) and HAESA-LIKE2 (HSL2)
      activates organ abscission in Arabidopsis flowers. Another set of receptor-like
      kinases, including EVERSHED (EVR), restricts the extent of cell separation in
      abscission zones by potentially altering HAE/HSL2 localization or activity. The
      NEVERSHED (NEV) ADP-ribosylation factor GTPase-activating protein facilitates the
      intracellular movement of molecules required for organ abscission and fruit
      growth. Here we report further analysis of the relationship between NEV-mediated
      intracellular traffic, EVR activity and IDA-HAE/HSL2 signaling during flower
      development. Our results support a model in which cell separation is mediated by
      HAE/HSL2 signaling downstream of NEV and EVR. We discuss the possibility that
      conserved circuits control organ abscission and modulate fruit growth.

PMID- 25763491
TI  - Interference of Brefeldin A in viral movement protein tubules assembly.
AB  - Plant virus genomes cross the barrier of the host cell wall and move to
      neighboring cells either in the form of nucleoprotein complex or encapsidated
      into virions. Virus transport is facilitated by virus-encoded movement proteins
      (MP), which are different from one another in number, size, sequence, and in the
      strategy used to overcome the size exclusion limit of plasmodesmata (PD). (1) A
      group of them forms tubules inside the lumen of highly modified PDs upon removal
      of the desmotubule. To date the molecular mechanism(s) and the host factors
      involved in the assembly of MP tubules as well as the mechanistic aspects of
      virus particle transport throughout them remain substantially unknown. In a
      recent study, we showed that Cauliflower mosaic virus (CaMV) MP traffics in the
      endocytic pathway with the help of 3 tyrosine-sorting signals, which are not
      required to target MP to the plasma membrane but are essential for tubule
      formation. (2) This evidence unravels a previously unknown connection between the
      plant endosomal system and tubule-mediated virus movement that is here supported
      by demonstration of hindrance of tubule assembly upon Brefeldin A (BFA)
      treatment. We discuss the implications of our data on the mechanisms of viral
      transport through tubules and draw parallels with plant mechanisms of polarized
      growth. 

PMID- 25763492
TI  - Arabidopsis dual resistance proteins, both RPS4 and RRS1, are required for
      resistance to bacterial wilt in transgenic Brassica crops.
AB  - Bacterial wilt phytopathogen Ralstonia solanacearum is a serious soil-borne
      disease that attacks several economically important plants worldwide, including
      Brassicaceae. Previous studies indicate that recognition of avirulence (Avr)
      effector PopP2 by resistance (R) protein, RRS1-R, and physical interaction
      between RRS1-R and PopP2 in the nucleus are required for resistance. Of late, we
      showed that a pair of Arabidopsis thaliana TIR-NLR proteins, RRS1 and RPS4,
      function together in disease resistance against multiple pathogen isolates. Here,
      we report that dual R proteins, RRS1 and RPS4, from A. thaliana ecotype
      Wassilewskija confer resistance to bacterial wilt in transgenic Brassica crops.
      For practical applications, this finding may provide a new strategy for
      developing disease resistant plants that express R genes from other plants. 

PMID- 25763493
TI  - Phosphothreonine 218 is required for the function of SR45.1 in regulating flower
      petal development in Arabidopsis.
AB  - RNA splicing is crucial to the production of mature mRNAs (mRNA). In Arabidopsis
      thaliana, the protein Arginine/Serine-rich 45 (SR45) acts as an RNA splicing
      activator and initiates the spliceosome assembly. SR45 is alternatively spliced
      into 2 isoforms. Isoform 1 (SR45.1) plays an important role in the flower petal
      development whereas isoform 2 (SR45.2) is important for root growth. In this
      study, we used immunoprecipitation to isolate an SR45.1-GFP fusion protein from
      transgenic plants complementing a null mutant, sr45-1. Mass spectrometry
      suggested a single phosphorylation event in a peptide from the alternatively
      spliced region unique to SR45.1. Substituting alanine for threonine 218, a
      candidate site for phosphorylation, did not complement the sr45-1 mutant with
      narrow flower petals whereas substituting aspartic acid or glutamic acid for
      threonine 218 did complement the sr45-1 mutant. Mass spectrometry also revealed
      that other proteins involved in the spliceosome co-precipitated with SR45.1, and
      RT-qPCR revealed that phosphorylation of threonine 218 promotes the function of
      SR45.1 in promoting the constitutive splicing of SR30 mRNA. This is the first
      demonstration of a specific phosphorylation site that differentially regulates
      the function of a plant splicing activator in physiologically and morphologically
      distinct plant tissues. 

PMID- 25763494
TI  - ABA induces H2O2 production in guard cells, but does not close the stomata on
      Vicia faba leaves developed at high air humidity.
AB  - Plants developed under constant high (> 85%) relative air humidity (RH) have
      larger stomata that are unable to close completely. One of the hypotheses for the
      less responsive stomata is that the plants have reduced sensitivity to abscisic
      acid (ABA). Both ABA and darkness are signals for stomatal closure and induce the
      production of the secondary messenger hydrogen peroxide (H2O2). In this study,
      the ability of Vicia faba plants developed in moderate or high RH to close the
      stomata in response to darkness, ABA and H2O2 was investigated. Moreover, the
      ability of the plants to produce H2O2 when treated with ABA or transferred to
      darkness was also assessed. Our results show that the ABA concentration in
      moderate RH is not increased during darkness even though the stomata are closing.
      This indicates that stomatal closure in V. faba during darkness is independent of
      ABA production. ABA induced both H2O2 production and stomatal closure in stomata
      formed at moderate RH. H2O2 production, as a result of treatment with ABA, was
      also observed in stomata formed at high RH, though the closing response was
      considerably smaller as compared with moderate RH. In either RH, leaf ABA
      concentration was not affected by darkness. Similarly to ABA treatment, darkness
      elicited both H2O2 production and stomatal closure following plant cultivation at
      moderate RH. Contrary to this, neither H2O2 production nor stomatal closure took
      place when stomata were formed at high RH. These results suggest that the reduced
      stomatal response in plants developed in continuous high RH is caused by one or
      more factors downstream of H2O2 in the signaling pathway toward stomatal closure.

PMID- 25763495
TI  - The PHD-finger module of the Arabidopsis thaliana defense regulator EDM2 can
      recognize triply modified histone H3 peptides.
AB  - Recently we reported that the Arabidopsis thaliana PHD-finger protein EDM2
      (enhanced downy mildew 2) impacts disease resistance by affecting levels of di
      methylated lysine 9 of histone H3 (H3K9me2) at an alternative polyadenylation
      site in the immune receptor gene RPP7. EDM2-dependent modulation of this post
      translational histone modification (PHM) shifts the balance between full-length
      RPP7 transcripts and prematurely polyadenylated transcripts, which do not encode
      the RPP7 protein. Our previous work genetically linked, for the first time, PHMs
      to alternative polyadenylation and established EDM2 as a critical component
      mediating PHM-dependent polyadenylation control. However, how EDM2 is recruited
      to its genomic target sites and how it affects H3K9me2 levels is unknown. Here we
      show the PHD-finger module of EDM2 to recognize histone H3 bearing certain
      combinations of 3 distinct PHMs. Our results suggest that targeting of EDM2 to
      specific genomic regions is mediated by the histone-binding selectivity of its
      PHD-finger domain. 

PMID- 25763496
TI  - Glucose and phytohormone interplay in controlling root directional growth in
      Arabidopsis.
AB  - Sensing and responding toward gravity vector is a complicated and multistep
      process. Gravity is a constant factor feeding plants with reliable information
      for the spatial orientation of their organs. Auxin, cytokinin, ethylene and BRs
      have been the most explored hormones in relation to gravitropism. We have
      previously shown that glucose (Glc) could promote brassinosteroid (BR) signaling
      thereby inducing changes in root directional growth. Auxin signaling and polar
      transport components are also involved in Glc induced changes in root directional
      growth. Here, we provide evidence for involvement of cytokinin and ethylene
      signaling components in regulation of root directional growth downstream to Glc
      and BR. Altogether, Glc mediated change in root direction is an adaptive feature
      which is a result of a collaborative effort integrating phytohormonal signaling
      cues. 

PMID- 25763497
TI  - The roles of anion channels in Arabidopsis immunity.
AB  - Anion efflux is one of the most immediate responses of plant cells to pathogen
      attacks, suggesting that anion channels may play a role in plant defense.
      Recently we reported that the chloride channel AtCLCd negatively regulates
      Arabidopsis pathogen-associated molecular pattern-triggered immunity (PTI),
      probably by affecting trafficking of the pattern recognition receptors (PRRs).
      Since AtCLCd is localized to the trans-Golgi network, it is not likely to be
      directly involved in anion flux across the plasma membrane. Here, we used a
      pharmacological approach to explore further the function of plasma membrane
      localized R-type and S-type anion channels in plant immunity. We found that the R
      type and S-type anion channels play opposite roles in Arabidopsis innate
      immunity. Inhibition of the R-type anion channels enhances, whereas inhibition of
      the S-type channels inhibits PTI and effector-triggered immunity (ETI). 

PMID- 25763498
TI  - Multiple roles of plant volatiles in jasmonate-induced defense response in rice.
AB  - The plant hormone jasmonic acid (JA) has a crucial role in defense responses
      against pathogens in rice. We recently reported that some volatile compounds
      accumulate in response to JA treatment, and that the monoterpene linalool plays
      an important role in JA-induced resistance to rice bacterial blight caused by
      Xanthomonas oryzae pv oryzae (Xoo) in rice. One of the JA-responsive volatiles,
      (E,E)-2,4-heptadienal, has both antibacterial and antifungal activity against
      Xoo, and the rice fungal pathogen Magnaporthe oryzae. In addition, (E,E)-2,4
      heptadienal was toxic to rice plants. These phenomena were not observed when
      linalool was treated. These results indicate that accumulation of the (E,E)-2,4
      heptadienal in response to JA is a double-edged sword, but it is essential for
      survival against pathogen attacks in rice. 

PMID- 25763499
TI  - Proportion of phospholipids in the plasma membrane is an important factor in Al
      tolerance.
AB  - The negative charge on the plasma membrane (PM) is mainly derived from the
      phosphate group of phospholipids. One of the mechanisms of aluminum (Al) toxicity
      is to increase the PM permeability of root cells by binding to the negative sites
      on the PM. Thus, PM with a higher proportion of phospholipids could be more
      susceptible to Al toxicity. In our previous study, we showed that tolerance to Al
      and low-calcium in rice was enhanced by decreasing the proportion of
      phospholipids in root cells. Both Melastoma malabathricum L. and Melaleuca
      cajuputi Powell are dominant woody species that grow in tropical acid sulfate
      soils, and have been reported to be more tolerant to Al than rice. Surprisingly,
      the proportion of PM phospholipids in root cells of M. malabathricum and M.
      cajuputi was considerably low. Our present findings suggest that PM lipid
      composition plays an important role in Al tolerance mechanisms in various plant
      species. 

PMID- 25763500
TI  - CLE peptides regulate lateral root development in response to nitrogen
      nutritional status of plants.
AB  - CLE (CLAVATA3/embryo surrounding region (ESR)) peptides control meristem
      functions in plants. Our recent study highlights the critical role of a peptide
      receptor signaling module composed of nitrogen (N)-responsive CLE peptides and
      the CLAVATA1 (CLV1) leucine-rich repeat receptor-like kinase in controlling
      lateral root development in Arabidopsis thaliana. CLE1, -3, -4 and -7 are
      expressed in root pericycle cells in Arabidopsis roots under N-limited growth
      conditions. Overexpression of these CLE genes inhibits lateral root emergence
      from the primary root. The inhibitory action of N-responsive CLE peptides on
      lateral root development requires the function of CLV1 expressed in phloem
      companion cells in roots, suggesting that downstream signals are transferred
      through phloem for systemic regulation of root system architecture. An additional
      mechanism downstream of CLV1 feedback-regulates transcript levels of N-responsive
      CLE genes in roots for fine-tuning the signal amplitude.

PMID- 25763501
TI  - Turning moss into algae: prenylation targets in Physcomitrella patens.
AB  - Prenylation is a series of lipid posttranslational modifications that are
      involved in several key aspects of plant development. We recently knocked out
      every prenylation subunit in Physcomitrella patens. Like in Arabidopsis, knockout
      of protein farnesyltransferase and protein geranylgeranyltransferase in P. patens
      does not result in lethality; however, effects on development are extensive. In
      particular, the knockout of protein geranylgeranyltransferase results in small
      unicellular plants that resemble algae. Here we perform an analysis of predicted
      geranylgeranyltransferase target proteins in P. patens, and draw attention to
      those most likely to play a role in the knockout phenotype. 

PMID- 25763502
TI  - A novel Azotobacter vinellandii (SRIAz3) functions in salinity stress tolerance
      in rice.
AB  - The plant growth promoting rhizobacteria (PGPRs) as a biofertilizer provide
      agricultural benefits to advance various crops productivity. Recently, we
      discovered a novel Azotobacter vinellandii (SRIAz3) from rice rhizosphere, which
      is well competent to improve rice productivity. In this study, we investigated a
      role of A. vinellandii to confer salinity tolerance in rice (var. IR64). A.
      vinellandii inoculated rice plants showed higher proline and malondialdehyde
      content under 200 mM NaCl stress as compared with uninoculated one. The
      endogenous level of plant hormones viz., indole-3 acetic acid (IAA), gibberellins
      (GA3), zeatint (Zt) was higher in A. vinellandii inoculated plants under high
      salinity. The fresh biomass of root and shoot were relatively elevated in A.
      vinellandii inoculated rice. Further, the macronutrient profile was superior in
      A. vinellandii inoculated plants under salinity as compared with non-inoculated
      plants. The present findings further suggest that A. vinellandii, a potent
      biofertilzer, potentially confer salinity stress tolerance in rice via sustaining
      growth and improving compatible solutes and nutrients profile and thereby crop
      improvement. 

PMID- 25763504
TI  - The Rescue of the Aesthetic Character of Existence in Kierkegaard Philosophy.
AB  - The intention of this article is to develop considerations regarding the unity in
      all that constitutes the multifaceted work of Soren Kierkegaard. The guides to
      the subject of this investigation are the stages of existence. His work is
      devoted to considering the unity of all spheres in their original place, which is
      concrete existence. To search for this unity, Kierkegaard resumes the aesthetic
      element of existence, which had been abandoned since the Greeks, passing by
      Christianity and radicalizing itself since philosophers of subjectivity, to show
      that this abandon provokes the suppression of the aesthetic element, without
      which oneness is not possible. 

PMID- 25763505
TI  - The Influence of Religion and Ethnicity on Family Planning Approval: A Case for
      Women in Rural Western Kenya.
AB  - The role of sociocultural factors such as religion and ethnicity in aiding or
      hampering family planning (FP) uptake in rural Western Kenya, a region with
      persistently high fertility rates, is not well established. We explored whether
      attitudes towards FP can be attributed to religious affiliation and/or ethnicity
      among women in the region. Findings show that religion and ethnicity have no
      impact; the most significant factors are level of education and knowledge about
      the benefits of FP for the mother. FP interventions ought to include strategies
      aimed at enhancing women's knowledge about the positive impacts of family
      planning. 

PMID- 25763506
TI  - Thermomechanical transitions of egg-ceramide monolayers.
AB  - Ceramides have unique biophysical properties. Their high melting temperature and
      their ability to form lateral domains have converted ceramides into the paradigm
      of rigid lipids. Here, using shear surface rheology of egg-ceramide Langmuir
      monolayers, a solid to fluid transition was evidenced as a vanishing shear
      rigidity at lower temperatures than the lipid melting temperature. Such a
      mechanical transition, which depends on the lipid lateral pressure, was found in
      a broad range temperature (40-50  degrees C). The solid to fluid transition was
      correlated to a LC to LC+LE phase transition, as confirmed by BAM experiments.
      Interestingly, together with the softening transition, a supercooling process
      compatible with a glassy behavior was found upon freezing. A new phase scenario
      is then depicted that broadens the mechanical behavior of natural ceramides. The
      phase diversity of ceramides might have important implications in their
      physiological roles. 

PMID- 25763507
TI  - Perceptual Estimates of Motor Skill Proficiency Are Constrained by the Stability
      of Coordination Patterns.
AB  - This study demonstrated that motor skill proficiency ratings are constrained by
      the same order parameter dynamics that constrain action production and action
      perception processes. Participants produced rhythmic actions simulated by an
      animated stick figure of the human arm. The primary finding was that
      participants' proficiency ratings covaried most with relative phase (phi)
      variability compared to mean relative phase. In-phase (phi = 0 degrees ) was
      produced with the least variability and received the highest proficiency rating,
      whereas the patterns phi = +/-150 degrees  were attempted with the most
      variability and received the lowest proficiency ratings. A temporal delay in
      attempting to produce the animated pattern had a large impact on produced
      relative phase, yet had little impact on the proficiency ratings. Proprioceptive
      processes provide individuals information on motor skill proficiency. The lead or
      lag motion of the hand to forearm segment of the animated arm was identified
      consistently through visual processes and revealed asymmetries in the mapping of
      visual input to motor output. The results are consistent with concepts from the
      dynamic pattern theory of coordination and are discussed with regard to relative
      phase as an informational variable that constraints the perception-action system
      across many levels. 

PMID- 25763508
TI  - Combined Sepiapterin Reductase and Methylmalonyl-CoA Epimerase Deficiency in a
      Second Patient: Cerebrospinal Fluid Polyunsaturated Fatty Acid Level and Follow
      Up Under L-DOPA, 5-HTP and BH4 Trials.
AB  - Objective/context: We describe the second patient presenting the combination of
      two homoallelic homozygous nonsense mutations in two genes distant from 1.8 Mb in
      the chromosome 2p13-3, the methylmalonyl-CoA epimerase gene (MCEE) and the
      sepiapterin reductase gene (SPR). CASE REPORT: The patient was born from
      consanguineous parents. He has presented a moderate but constant methylmalonic
      acid (MMA) excretion in urine associated with a mental retardation. The first
      homozygous mutation was identified in the MCEE gene (c.139C>T; p.Arg47*).
      Progressive dystonia and cataplexy narcolepsy led to diagnose the second
      homozygous mutation in the SPR gene: c.751A>T; p.Lys251*. Sepiapterin reductase
      deficiency (SRD) was characterized by a defect in tetrahydrobiopterin (BH4), the
      cofactor of several hydroxylases needed for the synthesis of neurotransmitters. A
      treatment with L-DOPA/carbidopa and 5-HTP dramatically improved the dystonic
      posture, the mood and the hypersomnia, proving that the pathogenesis was due to
      SRD. A supplementation with BH4 did not induce additional clinical benefit,
      although HVA and HIAA increased in CSF. The polyunsaturated fatty acids were
      measured in CSF as the markers of the neuronal stress. We have shown that DHA and
      its precursor EPA were high before and during the time course of the different
      treatments. IN CONCLUSION: The patient has inherited two copies of the two
      mutations from his consanguineous parents in the MCEE and SPR genes in the
      chromosome 2p13-3. DHA and EPA increased in CSF as a response to the neuronal
      stress induced by the defect in neurotransmitters or the altered metabolism of
      the odd-chain fatty acids and cholesterol.

PMID- 25763509
TI  - Bladder and Bowel Dysfunction Is Common in Both Men and Women with Mutation of
      the ABCD1 Gene for X-Linked Adrenoleukodystrophy.
AB  - BACKGROUND: X-linked adrenoleukodystrophy (X-ALD) is a disorder caused by
      mutations in the ABCD1 gene. The commonest phenotype of X-ALD is
      adrenomyeloneuropathy (AMN), which is characterised by involvement of the spinal
      cord and peripheral nerves. The aim of this study was to evaluate bladder and
      bowel symptoms in men with AMN and female X-ALD carriers. METHODS: In this cross
      sectional study, patients with confirmed mutation of the ABCD1 gene attending a
      tertiary care service were approached about bladder and bowel complaints and
      completed the Urinary Symptom Profile (USP), Qualiveen Short Form (SF-Qualiveen),
      International Prostate Symptom Score (IPSS) and Neurogenic Bowel Dysfunction
      (NBD) questionnaires. Neurological disability was assessed using the Expanded
      Disability Status Scale (EDSS). RESULTS: Forty-eight patients participated, 19
      males (mean EDSS score (n = 16) 5.0 (95% CI +/- 1.03)) and 29 females (mean EDSS
      score (n = 25) 3.2 (95% CI +/- 0.98)). Overactive bladder (OAB) symptoms were
      reported in both males (100%, n = 19) and females (86.2%, n = 25). There was no
      significant gender difference in severity of OAB symptoms (P = 0.35) and impact
      on quality of life (P = 0.13). Furthermore, there was no significant difference
      in OAB severity when symptoms were compared between female carriers and a cohort
      of women (n = 17) with spinal cord damage due to multiple sclerosis (P = 0.27).
      Twenty-one percent (n = 4) of males and 10% (n = 3) of females had moderate to
      severe bowel dysfunction. CONCLUSIONS: Bladder and bowel complaints are common in
      both men with AMN and female carriers. They have a significant impact on the
      quality of life yet are under-reported and under-treated. Though having an X
      linked pattern of inheritance, female carriers may experience overactive bladder
      symptoms which are as severe as in male patients and are likely to be
      neurological in origin.

PMID- 25763510
TI  - Extreme Contrast of Postprandial Remnant-Like Particles Formed in
      Abetalipoproteinemia and Homozygous Familial Hypobetalipoproteinemia.
AB  - BACKGROUND: Familial hypobetalipoproteinemia (FHBL) and abetalipoproteinemia
      (ABL) are rare inherited forms of hypolipidemia. Their differential diagnosis is
      important for predicting of the prognosis and selecting appropriate therapy.
      MATERIALS AND METHODS: Genetic analysis was performed in two patients with
      primary hypocholesterolemia born from consanguineous parents. The oral fat
      tolerance test (OFTT) was performed in one patient with FHBL (apoB-87.77) and one
      with ABL as well as in four normal control subjects. After overnight fasting,
      blood samples were drawn. Serum lipoprotein and remnant-like particle (RLP)
      fractions were determined by HPLC analysis. RESULTS: Both patients with
      homozygous FHBL were asymptomatic probably because of preserved levels of fat
      soluble vitamins, especially vitamin E. The patients with FHBL were homozygous
      because of novel apoB-83.52 and apoB-87.77 mutations, and although one of them
      (apoB-87.77) had fatty liver disease, microscopic findings suggesting
      nonalcoholic steatohepatitis were absent. Fasting apoB-48 and RLP-triglyceride
      levels in the patient with homozygous FHBL, which were similar to those in normal
      control subjects, increased after OFTT both in normal control subjects and the
      patient with FHBL but not in the patient with ABL, suggesting that the fat load
      administered was absorbed only in the patient with FHBL. CONCLUSION: Although
      lipid levels in the patients with homozygous FHBL and ABL were comparable,
      fasting, postoral fat loading of apoB-48, as well as RLP-triglyceride levels, may
      help in the differential diagnosis of FHBL and ABL and provide a prompt diagnosis
      using genetic analysis in the future.

PMID- 25763511
TI  - Postmortem Findings and Clinical Correlates in Individuals with Infantile-Onset
      Pompe Disease.
AB  - Pompe disease (OMIM 232300), a glycogen storage disorder caused by deficiency in
      the lysosomal enzyme acid alpha-glucosidase (EC 3.2.1.20), results in weakness
      and cardiomyopathy in infants affected with the classic form. Although the
      primary disease manifestations are due to glycogen accumulation in skeletal and
      cardiac muscle, glycogen also accumulates in a variety of additional tissues. To
      improve our understanding of disease pathogenesis in long-term survivors, we
      reviewed postmortem results for three infants with the classic form of Pompe
      disease. We have observed a number of new complications in long-term survivors of
      infantile-onset Pompe disease, and we focused this postmortem study on
      pathological correlates. Findings in survivors include cardiac arrhythmias, which
      may be related to glycogen accumulation in cardiac conduction tissue; urinary
      incontinence, likely due to glycogen accumulation in smooth muscle; and
      refractory errors, possibly related to accumulation in ocular structures. These
      observations provide potential pathophysiologic correlates for complications in
      long-term survivors of infantile Pompe disease. 

PMID- 25763512
TI  - Abnormal Newborn Screening in a Healthy Infant of a Mother with Undiagnosed
      Medium-Chain Acyl-CoA Dehydrogenase Deficiency.
AB  - A neonate with low blood free carnitine level on newborn tandem mass spectrometry
      screening was evaluated for possible carnitine transporter defect (CTD). The
      plasma concentration of free carnitine was marginally reduced, and the
      concentrations of acylcarnitines (including C6, C8, and C10:1) were normal on
      confirmatory tests. Organic acids in urine were normal. In addition, none of the
      frequent Faroese SLC22A5 mutations (p.N32S, c.825-52G>A) which are common in the
      Danish population were identified. Evaluation of the mother showed low-normal
      free carnitine, but highly elevated medium-chain acylcarnitines (C6, C8, and
      C10:1) consistent with medium-chain acyl-CoA dehydrogenase deficiency (MCADD).
      The diagnosis was confirmed by the finding of homozygous presence of the c.985A>G
      mutation in ACADM. 

PMID- 25763513
TI  - Lentiginous melanoma. A clinically malignant entity that histopathologically
      seems benign. Case study harbouring BRAF(V) (600R) mutation.

PMID- 25763514
TI  - Ethical implications of patients and families secretly recording conversations
      with physicians.

PMID- 25763515
TI  - Repeatability of Respiratory Exchange Ratio Time Series Analysis.
AB  - Currently, there are few studies on the repeatability of a time series analysis
      of respiratory exchange ratio (RER) under the same conditions. This repeated
      measures study compared 2 trials completed under the same conditions. After an 8
      hour fast, subjects (7 male and 5 female) (mean +/- SD) of age 27.3 +/- 3.7
      years, body weight of 71.8 +/- 8.4 kg, percent body fat of 16.4 +/- 8.1%, and
      peak oxygen uptake (V[Combining Dot Above]O2peak) of 46.0 +/- 5.3 ml.kg.min
      completed a V[Combining Dot Above]O2peak test followed 7 days later by a cycle
      ergometer test at 30% of ventilatory threshold (VT) and 60% of VT for 15 minutes
      each. These tests were repeated again 7 days later. Paired t-tests revealed no
      significant differences between the tests for mean RER or sample entropy (SampEn)
      score at both intensities. The coefficients of variance were generally similar
      for the mean and SampEn of the RER. The intraclass correlation coefficient (ICC)
      values for the mean RER at 30% of VT were 1.00 and at 60% of VT were 0.92. The
      ICC values for the SampEn RER at 30% of VT were 0.81 and at 60% of VT were the
      lowest at 0.25. Bland-Altman plots demonstrated a measure of agreement between
      both methods. We demonstrated that RER measurements at 30 and 60% of VT are
      repeatable during steady-state cycle ergometery. Future research should determine
      if this finding is consistent with a larger sample size and different exercise
      intensities.

PMID- 25763516
TI  - A New Tool to Assess the Perception of Stretching Intensity.
AB  - This study aimed to develop a valid and reliable scale to assess the perception
      of stretching intensity below and above the maximal range of motion. Experiments
      were conducted through a passive leg extension angle-torque assessment to healthy
      population (n = 90). In the study's first phase, the visual, numerical, and
      description of the stretching intensity scale (SIS) components were developed.
      The visual analog scale (VAS) score, absolute magnitude estimation (AME) score,
      and verbal stretching intensity symptom descriptors were assessed for different
      stretching intensities. In the second phase, the SIS was tested for validity,
      reliability, scale production, and estimation properties as well as
      responsiveness to stretching. In the first phase, a high correlation was found
      between SIS score and range of motion (ROM), as well as SIS and torque in both
      submaximal (intraclass correlation coefficient [ICC] = 0.89-0.99, r = 0.88-0.99)
      and supramaximal (ICC = 0.75-0.86, r = 0.68-0.88) stretching intensities. The AME
      and VAS scores fitted well in an exponential model for submaximal stretching
      intensities (y = 14.829e, ICC = 0.97 [0.83-0.99], r = 0.98), and in a linear
      model for supramaximal stretching intensities (y = 0.7667x - 25.751, ICC = 0.97
      [0.89-0.99], r = 0.9594). For the second phase, a high correlation was found
      between SIS score and ROM (r = 0.70-0.76, ICC = 0.76-0.85), as well as SIS and
      torque (r = 0.62-0.88, ICC = 0.57-0.85). The interday reliability was high to
      produce (r = 0.70, ICC = 0.70 [0.50-0.83]) or estimate (r = 0.89, ICC = 0.89
      [0.82-0.93]) stretching intensities. The acute stretching effects on ROM and
      passive torque were detectable using the SIS. It is expected a high application
      in assessing the stretch intensity using the SIS in future studies and practical
      interventions.

PMID- 25763517
TI  - Relationship Between Lower Limb Muscle Activity and Platform Acceleration During
      Whole-Body Vibration Exercise.
AB  - The purpose of this study was to identify the influence of different magnitudes
      and directions of the vibration platform acceleration on surface electromyography
      (sEMG) during whole-body vibration (WBV) exercises. Therefore, a WBV platform was
      used that delivers vertical vibrations by a side-alternating mode, horizontal
      vibrations by a circular mode, and vibrations in all 3 planes by a dual mode.
      Surface electromyography signals of selected lower limb muscles were measured in
      30 individuals while they performed a static squat on a vibration platform. The
      WBV trials included 2 side-alternating trials (Side-L: 6 Hz, 2.5 mm; Side-H: 16
      Hz, 4 mm), 2 circular trials (Circ-L: 14 Hz, 0.8 mm; Circ-H: 43 Hz, 0.8 mm), and
      4 dual-mode trials that were the combinations of the single-mode trials (Side
      L/Circ-L, Side-L/Circ-H, Side-H/Circ-L, Side-H/Circ-H). Furthermore, control
      trials without vibration were assessed, and 3-dimensional platform acceleration
      was quantified during the vibration. Significant increases in the root mean
      square of the sEMG (sEMGRMS) compared with the control trial were found in most
      muscles for Side-L/Circ-H (+17 to +63%, p <= 0.05), Side-H/Circ-L (+7 to +227%, p
      <= 0.05), and Side-H/Circ-H (+21 to +207%, p < 0.01) and in the lower leg muscles
      for Side-H (+35 to +138%, p <= 0.05). Furthermore, only the vertical platform
      acceleration showed a linear relationship (r = 0.970, p < 0.001) with the
      averaged sEMGRMS of the lower limb muscles. Significant increases in sEMGRMS were
      found with a vertical acceleration threshold of 18 m.s(-2) and higher. The
      present results emphasize that WBV exercises should be performed on a platform
      that induces vertical accelerations of 18 m.s(-2) and higher.

PMID- 25763518
TI  - Exercise-Based Performance Enhancement and Injury Prevention for Firefighters:
      Contrasting the Fitness- and Movement-Related Adaptations to Two Training
      Methodologies.
AB  - Using exercise to enhance physical fitness may have little impact on performers'
      movement patterns beyond the gym environment. This study examined the fitness and
      movement adaptations exhibited by firefighters in response to 2 training
      methodologies. Fifty-two firefighters were assigned to a movement-guided fitness
      (MOV), conventional fitness (FIT), or control (CON) group. Before and after 12
      weeks of training, participants performed a fitness evaluation and laboratory
      based test. Three-dimensional lumbar spine and frontal plane knee kinematics were
      quantified. Five whole-body tasks not included in the interventions were used to
      evaluate the transfer of training. FIT and MOV groups exhibited significant
      improvements in all aspects of fitness; however, only MOV exhibited improvements
      in spine and frontal plane knee motion control when performing each transfer task
      (effect sizes [ESs] of 0.2-1.5). FIT exhibited less controlled spine and frontal
      plane knee motions while squatting, lunging, pushing, and pulling (ES: 0.2-0.7).
      More MOV participants (43%) exhibited only positive posttraining changes (i.e.,
      improved control), in comparison with FIT (30%) and CON (23%). Fewer negative
      posttraining changes were also noted (19, 25, and 36% for MOV, FIT, and CON).
      These findings suggest that placing an emphasis on how participants move while
      exercising may be an effective training strategy to elicit behavioral changes
      beyond the gym environment. For occupational athletes such as firefighters,
      soldiers, and police officers, this implies that exercise programs designed with
      a movement-oriented approach to periodization could have a direct impact on their
      safety and effectiveness by engraining desirable movement patterns that transfer
      to occupational tasks.

PMID- 25763519
TI  - Kinematic and sEMG Analysis of the Back Squat at Different Intensities With and
      Without Knee Wraps.
AB  - The purposes of this study were to measure the acute effects of knee wraps (KWs)
      on knee and hip joint kinematics, dynamic muscle activation from the vastus
      lateralis (VL) and gluteus maximus (GM), and rating of perceived exertion (RPE)
      during the back squat exercise at 2 different intensities. Fourteen resistance
      trained men (age: 24 +/- 4 years, height: 176 +/- 6 cm, body mass: 81 +/- 11 kg,
      back squat 1 repetition maximum [1RM]: 107 +/- 30 kg, 3 +/- 1 year of back squat
      experience) performed 1 set of 3 repetitions under 4 different conditions, to a
      depth of approximately 90 degrees of knee joint flexion, and in random order: KWs
      at 60% 1RM (KW60), KWs at 90% 1RM (KW90), without knee wraps (NWs) at 60% 1RM
      (NW60), and NWs at 90% 1RM (NW90). The dependent variables obtained were vertical
      and horizontal bar displacement, peak joint angle in the sagittal plane (hip and
      knee joints), concentric and eccentric muscle activation (by integrated
      electromyography) from the VL and GM, and RPE. For muscle activity, there were
      significant decreases in the VL NWs at 60% 1RM (p = 0.013) and a significant
      increase NWs at 90% 1RM (p = 0.037). There was a significant increase in VL
      muscle activity at 90% 1RM, when compared with 60% 1RM (KW: p = 0.001, effect
      size (ES) = 1.51 and NW: p < 00.001, ES = 1.67). There was a decrease in GM
      muscle activity NWs only at 60% 1RM (p = 0.014). There was a significant increase
      in GM muscle activity at 90% 1RM, when compared with 60% 1RM (KW: p < 0.001 and
      NW: p < 0.001). For peak hip joint flexion angle, there was significant decreases
      between intensities (90% 1RM < 60% 1RM) only to NWs condition (p = 0.009), and
      there was greater knee flexion NWs for both intensities: 60% 1RM (p < 0.001) and
      90% 1RM (p = 0.018). For normalized vertical barbell displacement, there were
      significant differences between intensities when using KWs (p = 0.022). There
      were significant differences in RPE between 60 and 90% 1RM for each condition:
      KWs (p < 0.001) and NWs (p < 0.001). In conclusion, the use of KWs results in
      decreased muscle activation of the VL at the same intensity (90% 1RM).

PMID- 25763520
TI  - The Kansas Squat Test: A Valid and Practical Measure of Anaerobic Power for Track
      and Field Power Athletes.
AB  - The Kansas squat test (KST) is a repetitive lifting test designed to measure
      relatively similar indices of lower-body power as the Wingate anaerobic test
      (WAnT). The purposes of this study were twofold: determine concurrent validity of
      the KST using the WAnT as the criterion measure and also demonstrate the KST as a
      practical test of anaerobic power for track and field athletes. Twenty-three
      track and field athletes participated (mean +/- SD; 77.2 +/- 16.8 kg, 175.6 +/-
      8.7 cm). Each completed the KST, and on a separate occasion, the WAnT for
      comparison. Correlation coefficients indicated significant relationships between
      the KST and the WAnT on measures of maximum test power (r = 0.920, p < 0.01) and
      mean test power (r = 0.929, p < 0.01), but not for relative fatigue (r = 0.030, p
      > 0.05). The posttest lactate response also lacked a significant relationship (r
      = -0.062, p > 0.05). These relationships were also present when athletes were
      examined in subgroups based on gender and event. Paired-samples t-tests indicated
      that while peak power and mean power were significantly higher for the KST (p <=
      0.01), relative fatigue and lactate were both significantly higher for the WAnT
      (p <= 0.01). These significant differences were similar in the subsequent
      subgroupings of the athletes. These data support that the KST is a concurrently
      valid assessment of lower-body anaerobic power. This study further illustrates a
      practical lower-body power testing method that is lift specific, which may aid in
      improving training specificity for track and field power athletes.

PMID- 25763521
TI  - Increasing Ball Velocity in the Overhead Athlete: A Meta-analysis of Randomized
      Controlled Trials.
AB  - Overhead athletes routinely search for ways to improve sport performance, and one
      component of performance is ball velocity. The purpose of this meta-analysis was
      to investigate the effect of different strengthening interventions on ball and
      serve velocity. A comprehensive literature search with pre-set inclusion and
      exclusion criteria from 1970 to 2014 was conducted. Eligible studies were
      randomized control trials including the mean and SDs of both pretest and posttest
      ball velocities in both the experimental and the control groups. The outcome of
      interest was ball/serve velocity in baseball, tennis, or softball athletes. Level
      2 evidence or higher was investigated to determine the effect different training
      interventions had on velocity. Pretest and posttest data were extracted to
      calculate Hedges's g effect sizes with 95% confidence intervals (CIs).
      Methodological qualities of the final 13 articles within the analysis were
      assessed using the Physiotherapy Evidence Database scale. The majority of the
      articles included in this analysis had an effect on velocity with the strongest
      effect sizes found in periodized training (Hedges's g = 3.445; 95% CI = 1.976
      4.914). Six studies had CI that crossed zero, indicating that those specific
      interventions should be interpreted with caution. Consistent and high-quality
      evidence exists that specific resistance training interventions have an effect on
      velocity. These findings suggest that interventions consisting of isokinetic
      training, multimodal training, and periodization training are clinically
      beneficial at increasing velocity in the overhead athlete over different windows
      of time.

PMID- 25763522
TI  - Trace element contamination in nestling black-tailed gulls (Larus crassirostris)
      in Korea.
AB  - At Hongdo Island, Gyeongsangnam-do, Korea, a breeding site of black-tailed gull
      (Larus crassirostris), we collected nestlings from two locations: a "reference"
      site (n = 10) with no known source of lead contamination and "lighthouse" site (n
      = 10) with suspected lead contamination from leaded paint. Iron concentrations in
      the kidney and bone, manganese in the muscle, copper in the bone, lead in the
      muscle and bone, and cadmium in the liver, muscle, and bone at the reference site
      were significantly higher than at the lighthouse. Manganese concentrations in the
      liver and kidney, and lead in the kidney were significantly greater at the
      lighthouse than at the reference site. Iron, zinc, manganese, copper, lead and
      cadmium concentrations had tissue-specific accumulation at both sites. Lead
      concentrations in 10 % of livers and in 80 % of kidneys at the lighthouse, and in
      20 % of livers from the reference were within a range considered toxic (>6.00
      MUg/g dw in the liver and kidney). Lead concentrations in 50 % of black-tailed
      gull nestlings at the reference and 80 % nestlings at the lighthouse were greater
      in livers than in bones, which is suggestive of acute lead exposure. For cadmium,
      all liver and kidney concentrations from two sites were at a level considered
      background in birds. Cadmium concentrations of every sample were higher in
      kidneys than in livers, suggestive of chronic cadmium exposure. Lead
      concentrations in gull nestlings in the present study were relatively higher than
      other gull species worldwide, but cadmium concentrations were relatively lower. 

PMID- 25763524
TI  - An investigation of the role of parental request for self-correction of
      stuttering in the Lidcombe Program.
AB  - PURPOSE: The Lidcombe Program is a behavioural treatment for stuttering in
      children younger than 6 years that is supported by evidence of efficacy and
      effectiveness. The treatment incorporates parent verbal contingencies for stutter
      free speech and for stuttering. However, the contribution of those contingencies
      to reductions in stuttering in the program is unclear. METHOD: Thirty-four parent
      child dyads were randomized to two treatment groups. The control group received
      standard Lidcombe Program and the experimental group received Lidcombe Program
      without instruction to parents to use the verbal contingency request for self
      correction. Treatment responsiveness was measured as time to 50% stuttering
      severity reduction. RESULT: No differences were found between groups on primary
      outcome measures of the number of weeks and clinic visits to 50% reduction in
      stuttering severity. CONCLUSION: This clinical experiment challenges the
      assumption that the verbal contingency request for self-correction contributes to
      treatment efficacy. Results suggest the need for further research to explore this
      issue.

PMID- 25763523
TI  - Size-dependent ecotoxicity of barium titanate particles: the case of Chlorella
      vulgaris green algae.
AB  - Studies have been demonstrating that smaller particles can lead to unexpected and
      diverse ecotoxicological effects when compared to those caused by the bulk
      material. In this study, the chemical composition, size and shape, state of
      dispersion, and surface's charge, area and physicochemistry of micro (BT MP) and
      nano barium titanate (BT NP) were determined. Green algae Chlorella vulgaris
      grown in Bold's Basal (BB) medium or Seine River water (SRW) was used as
      biological indicator to assess their aquatic toxicology. Responses such as growth
      inhibition, cell viability, superoxide dismutase (SOD) activity, adenosine-5
      triphosphate (ATP) content and photosynthetic activity were evaluated. Tetragonal
      BT (~170 nm, 3.24 m(2) g(-1) surface area) and cubic BT (~60 nm, 16.60 m(2) g(
      1)) particles were negative, poorly dispersed, and readily aggregated. BT has a
      statistically significant effect on C. vulgaris growth since the lower
      concentration tested (1 ppm), what seems to be mediated by induced oxidative
      stress caused by the particles (increased SOD activity and decreased
      photosynthetic efficiency and intracellular ATP content). The toxic effects were
      more pronounced when the algae was grown in SRW. Size does not seem to be an
      issue influencing the toxicity in BT particles toxicity since micro- and nano
      particles produced significant effects on algae growth. 

PMID- 25763525
TI  - Family Nurture Intervention in the Neonatal Intensive Care Unit improves social
      relatedness, attention, and neurodevelopment of preterm infants at 18 months in a
      randomized controlled trial.
AB  - BACKGROUND: Preterm infants are at high risk for adverse neurodevelopmental and
      behavioral outcomes. Family Nurture Intervention (FNI) in the Neonatal Intensive
      Care Unit (NICU) is designed to counteract adverse effects of separation of
      mothers and their preterm infants. Here, we evaluate effects of FNI on
      neurobehavioral outcomes. METHODS: Data were collected at 18 months corrected age
      from preterm infants. Infants were assigned at birth to FNI or standard care
      (SC). Bayley Scales of Infant Development III (Bayley-III) were assessed for 76
      infants (SC, n = 31; FNI, n = 45); the Child Behavior Checklist (CBCL) for 57
      infants (SC, n = 31; FNI, n = 26); and the Modified Checklist for Autism in
      Toddlers (M-CHAT) was obtained for 59 infants (SC, n = 33; FNI, n = 26). RESULTS:
      Family Nurture Intervention significantly improved Bayley-III cognitive (p =
      .039) and language (p = .008) scores for infants whose scores were greater than
      85. FNI infants had fewer attention problems on the CBCL (p < .02). FNI improved
      total M-CHAT scores (p < .02). Seventy-six percent of SC infants failed at least
      one of the M-CHAT items, compared to 27% of FNI infants (p < .001). In addition,
      36% of SC infants versus 0% of FNI infants failed at least one social-relatedness
      M-CHAT item (p < .001). CONCLUSIONS: Family Nurture Intervention is the first
      NICU intervention to show significant improvements in preterm infants across
      multiple domains of neurodevelopment, social-relatedness, and attention problems.
      These gains suggest that an intervention that facilitates emotional interactions
      between mothers and infants in the NICU may be key to altering developmental
      trajectories of preterm infants.

PMID- 25763526
TI  - Diagnostic accuracy of diffusion-weighted magnetic resonance imaging versus
      positron emission tomography/computed tomography for early response assessment of
      liver metastases to Y90-radioembolization.
AB  - OBJECTIVES: Patients with hepatic metastases who are candidates for Y90
      radioembolization (Y90-RE) usually have advanced tumor stages with involvement of
      both liver lobes. Per current guidelines, these patients have usually undergone
      several cycles of potentially hepatotoxic systemic chemotherapy before Y90-RE is
      at all considered, requiring split (lobar) treatment sessions to reduce hepatic
      toxicity. Assessing response to Y90-RE early, that is, already after the first
      lobar session, would be helpful to avoid an ineffective and potentially
      hepatotoxic second lobar treatment. We investigated the accuracy with which
      diffusion- weighted magnetic resonance imaging (DWI-MRI) and positron emission
      tomography/computed tomography (PET/CT) can provide this information. METHODS: An
      institutional review board-approved prospective intraindividual comparison trial
      on 35 patients who underwent fluorodeoxyglucose PET/CT and DWI-MRI within 6 weeks
      before and 6 weeks after Y90-RE to treat secondary-progressive liver metastases
      from solid cancers (20 colorectal, 13 breast, 2 other) was performed. An increase
      of minimal apparent diffusion coefficient (ADCmin) or decrease of maximum
      standard uptake value (SUVmax) by at least 30% was regarded as positive response.
      Long-term clinical and imaging follow-up was used to distinguish true- from false
      response classifications. RESULTS: On the basis of long-term follow-up, 23 (66%)
      of 35 patients responded to the Y90 treatment. No significant changes of
      metastases size or contrast enhancement were observable on pretreatment versus
      posttreatment CT or magnetic resonance images.However, overall SUVmax decreased
      from 8.0 +/- 3.9 to 5.5 +/- 2.2 (P < 0.0001), and ADCmin increased from 0.53 +/-
      0.13 * 10(-3) mm2/s to 0.77 +/- 0.26 * 10(-3) mm2/s (P < 0.0001). Pretherapeutic
      versus posttherapeutic changes of ADCmin and SUVmax correlated moderately (r = 
      0.53). In 4 of the 35 patients (11%), metastases were fluorodeoxyglucose-negative
      such that no response assessment was possible by PET. In 25 (71%) of the 35
      patients, response classification by PET and DWI-MRI was concordant; in 6 (17%)
      of the 35, it was discordant. In 5 of the 6 patients with discordant
      classifications, follow-up confirmed diagnoses made by DWI. The positive
      predictive value to predict response was 22 (96%) of 23 for MRI and 15 (88%) of
      17 for PET. The negative predictive value to predict absence was 11 (92%) of 12
      for MRI and 10 (56%) of 18 for PET. Sensitivity for detecting response was
      significantly higher for MRI (96%; 22/23) than for PET (65%; 15/23) (P < 0.02).
      CONCLUSIONS: Diffusion-weighted magnetic resonance imaging appears superior to
      PET/CT for early response assessment in patients with hepatic metastases of
      common solid tumors. It may be used in between lobar treatment sessions to guide
      further management of patients who undergo Y90-RE for hepatic metastases.

PMID- 25763527
TI  - Letter to Veugelers, P.J. and Ekwaru, J.P., A statistical error in the estimation
      of the recommended dietary allowance for vitamin D. Nutrients 2014, 6, 4472-4475;
      doi:10.3390/nu6104472.

PMID- 25763528
TI  - Iodized salt sales in the United States.
AB  - Iodized salt has been an important source of dietary iodine, a trace element
      important for regulating human growth, development, and metabolic functions. This
      analysis identified iodized table salt sales as a percentage of retail salt sales
      using Nielsen ScanTrack. We identified 1117 salt products, including 701 salt
      blends and 416 other salt products, 57 of which were iodized. When weighted by
      sales volume in ounces or per item, 53% contained iodized salt. These findings
      may provide a baseline for future monitoring of sales of iodized salt. 

PMID- 25763529
TI  - Strawberry phytochemicals inhibit azoxymethane/dextran sodium sulfate-induced
      colorectal carcinogenesis in Crj: CD-1 mice.
AB  - Human and experimental colon carcinogenesis are enhanced by a pro-inflammatory
      microenvironment. Pharmacologically driven chemopreventive agents and dietary
      variables are hypothesized to have future roles in the prevention of colon cancer
      by targeting these processes. The current study was designed to determine the
      ability of dietary lyophilized strawberries to inhibit inflammation-promoted
      colon carcinogenesis in a preclinical animal model. Mice were given a single i.p.
      injection of azoxymethane (10 mg kg-1 body weight). One week after injection,
      mice were administered 2% (w/v) dextran sodium sulfate in drinking water for
      seven days and then an experimental diet containing chemically characterized
      lyophilized strawberries for the duration of the bioassay. Mice fed control diet,
      or experimental diet containing 2.5%, 5.0% or 10.0% strawberries displayed tumor
      incidence of 100%, 64%, 75% and 44%, respectively (p < 0.05). The mechanistic
      studies demonstrate that strawberries reduced expression of proinflammatory
      mediators, suppressed nitrosative stress and decreased phosphorylation of
      phosphatidylinositol 3-kinase, Akt, extracellular signal-regulated kinase and
      nuclear factor kappa B. In conclusion, strawberries target proinflammatory
      mediators and oncogenic signaling for the preventive efficacies against colon
      carcinogenesis in mice. This works supports future development of fully
      characterized and precisely controlled functional foods for testing in human
      clinical trials for this disease. 

PMID- 25763530
TI  - Vitamin A intake, serum vitamin D and bone mineral density: analysis of the Korea
      National Health and Nutrition Examination Survey (KNHANES, 2008-2011).
AB  - The association of high vitamin A intake and low bone mineral density (BMD) is
      still controversial. To determine the association of dietary vitamin A intake and
      serum 25-hydroxyvitamin D (25(OH)D) concentration with BMD, a total of 6481
      subjects (2907 men and 3574 women) aged >=50 years from the Korean National
      Health and Nutrition Examination Survey (2008-2011) were divided into groups
      according to dietary vitamin A intake (tertiles) and serum 25(OH)D (<50, 50-75,
      >75 nmol/L), and evaluated for BMD after adjusting for relevant variables. Mean
      dietary vitamin A intakes were 737 and 600 MUg RE (Retinol Equivalents) in men
      and women, respectively. Total hip and femoral neck BMD in men and lumbar spine
      BMD in women were both positively correlated with dietary vitamin A intake in
      subjects with serum 25(OH)D >75 nmol/L. Among men with serum 25(OH)D <50 nmol/L,
      both the top (mean 1353 MUg RE) and bottom (mean 218 MUg RE) tertiles of dietary
      vitamin A intake had lower BMD than the middle group (mean 577 MUg RE). In this
      population, BMD was the highest among men and women with serum 25(OH)D = 50-75
      nmol/L and that there were no differences in BMD by vitamin A intake in these
      vitamin D adequate groups. This cross-sectional study indicates that vitamin A
      intake does not affect bone mineral density as long as the serum 25(OH)D
      concentration is maintained in the moderate level of 50-75 nmol/L. 

PMID- 25763531
TI  - Effects of supplementation with the fat-soluble vitamins E and D on fasting flow
      mediated vasodilation in adults: a meta-analysis of randomized controlled trials.
AB  - The effects of fat-soluble vitamin supplementation on cardiovascular disease
      (CVD) risk are not clear. Therefore, we performed a meta-analysis to quantify
      effects of fat-soluble vitamin supplements on fasting flow-mediated vasodilation
      (FMD) of the brachial artery, a validated marker to assess CVD risk. Randomized
      placebo-controlled trials (RCTs) were identified by a systematic search till July
      2014. Seven RCTs studying the effects of vitamin E supplements (range: 300 to
      1800 IU per day) and nine RCTs examining the effects of vitamin D supplements,
      that involved, respectively, 303 and 658 adults, were included. No studies with
      carotenoid or vitamin K supplements were found. Vitamin E supplementation
      increased FMD vs. control by 2.42% (95% CI: 0.46% to 4.37%; p = 0.015). No
      effects of vitamin D supplementation were found (0.15%; 95% CI: -0.21% to 0.51%;
      p = 0.41). These effects did not depend on subject characteristics, treatment
      characteristics or technical aspects of the FMD measurement. However, no dose
      response relationship was evident for vitamin E, statistical significance
      depended on one study, while the levels of supplement were far above recommended
      intakes. The current meta-analysis, therefore, does not provide unambiguous
      evidence to support the use of fat-soluble vitamin supplements to improve fasting
      FMD in adults. 

PMID- 25763534
TI  - Millisecond Ordering of Block Copolymer Films via Photothermal Gradients.
AB  - For the promise of self-assembly to be realized, processing techniques must be
      developed that simultaneously enable control of the nanoscale morphology, rapid
      assembly, and, ideally, the ability to pattern the nanostructure. Here, we
      demonstrate how photothermal gradients can be used to control the ordering of
      block copolymer thin films. Highly localized laser heating leads to intense
      thermal gradients, which induce a thermophoretic force on morphological defects.
      This increases the ordering kinetics by at least 3 orders of magnitude compared
      to conventional oven annealing. By simultaneously exploiting the thermal
      gradients to induce shear fields, we demonstrate uniaxial alignment of a block
      copolymer film in less than a second. Finally, we provide examples of how control
      of the incident light field can be used to generate prescribed configurations of
      block copolymer nanoscale patterns. 

PMID- 25763532
TI  - Micronutrients in pregnancy in low- and middle-income countries.
AB  - Pregnancy is one of the more important periods in life when increased
      micronutrients, and macronutrients are most needed by the body; both for the
      health and well-being of the mother and for the growing foetus and newborn child.
      This brief review aims to identify the micronutrients (vitamins and minerals)
      likely to be deficient in women of reproductive age in Low- and Middle-Income
      Countries (LMIC), especially during pregnancy, and the impact of such
      deficiencies. A global prevalence of some two billion people at risk of
      micronutrient deficiencies, and multiple micronutrient deficiencies of many
      pregnant women in LMIC underline the urgency to establishing the optimal
      recommendations, including for delivery. It has long been recognized that
      adequate iron is important for best reproductive outcomes, including gestational
      cognitive development. Similarly, iodine and calcium have been recognized for
      their roles in development of the foetus/neonate. Less clear effects of
      deficiencies of zinc, copper, magnesium and selenium have been reported. Folate
      sufficiency periconceptionally is recognized both by the practice of providing
      folic acid in antenatal iron/folic acid supplementation and by increasing numbers
      of countries fortifying flours with folic acid. Other vitamins likely to be
      important include vitamins B12, D and A with the water-soluble vitamins generally
      less likely to be a problem. Epigenetic influences and the likely influence of
      micronutrient deficiencies on foetal origins of adult chronic diseases are
      currently being clarified. Micronutrients may have other more subtle,
      unrecognized effects. The necessity for improved diets and health and sanitation
      are consistently recommended, although these are not always available to many of
      the world's pregnant women. Consequently, supplementation programmes,
      fortification of staples and condiments, and nutrition and health support need to
      be scaled-up, supported by social and cultural measures. Because of the life-long
      influences on reproductive outcomes, including inter-generational ones, both
      clinical and public health measures need to ensure adequate micronutrient intakes
      during pregnancy, but also during adolescence, the first few years of life, and
      during lactation. Many antenatal programmes are not currently achieving this. We
      aim to address the need for micronutrients during pregnancy, the importance of
      micronutrient deficiencies during gestation and before, and propose the scaling
      up of clinical and public health approaches that achieve healthier pregnancies
      and improved pregnancy outcomes. 

PMID- 25763533
TI  - Macro- and micronutrients consumption and the risk for colorectal cancer among
      Jordanians.
AB  - OBJECTIVE: Diet and lifestyle have been reported to be important risk factors for
      the development of colorectal cancer (CRC). However, the association between
      total energy and nutrient intake and the risk of developing CRC has not been
      clearly explained. The aim of our study is to examine the relationship between
      total energy intake and other nutrients and the development of CRC in the
      Jordanian population. RESEARCH METHODS AND PROCEDURES: Dietary data was collected
      from 169 subjects who were previously diagnosed with CRC, and 248 control
      subjects (matched by age, gender, occupation and marital status). These control
      subjects were healthy and disease free. Data was collected between January 2010
      and December 2012, using interview-based questionnaires. Logistic regression was
      used to evaluate the association between quartiles of total energy, macro- and
      micronutrient intakes with the risk of developing CRC in our study population.
      RESULTS: Total energy intake was associated with a higher risk of developing CRC
      (OR = 2.60 for the highest versus lowest quartile of intake; 95% CI: 1.21-5.56, p
      trend = 0.03). Intakes of protein (OR = 3.62, 95% CI: 1.63-8.05, p-trend =
      0.002), carbohydrates (OR = 1.41, 95% CI: 0.67-2.99, p-trend = 0.043), and
      percentage of energy from fat (OR = 2.10, 95% CI: 0.38-11.70, p-trend = 0.009)
      significantly increased the risk for the development of CRC. Saturated fat,
      dietary cholesterol and sodium intake showed a significant association with the
      risk of developing CRC (OR = 5.23, 95% CI: 2.33-11.76; OR = 2.48, 95% CI: 1.18
      5.21; and OR = 3.42, 95% CI: 1.59-7.38, respectively), while vitamin E and
      caffeine intake were indicative of a protective effect against the development of
      CRC, OR = 0.002 (95% CI: 0.0003-0.011) and 0.023 (95%CI: 0.008-0.067),
      respectively. CONCLUSION: Our results suggest an increased risk for the
      development of CRC in subjects with high dietary intake of energy, protein,
      saturated fat, cholesterol, and sodium, and diets high in vitamin E and caffeine
      were suggestive of a protective effect against the risk of developing CRC.
      IMPACT: This is the first study in Jordan to suggest that it may be possible to
      reduce CRC risk by adjusting the intake of some macro-and micronutrients.

PMID- 25763535
TI  - Assessment of axillary lymph nodes in patients with breast cancer with diffusion
      weighted MR imaging in combination with routine and dynamic contrast MR imaging.
AB  - PURPOSE: To assess axillary lymph nodes in patients with breast cancer with
      diffusion-weighted MR imaging in combination with routine and dynamic contrast MR
      imaging. MATERIALS AND METHODS: Prospective study was conducted on 65 enlarged
      axillary lymph nodes in 34 consecutive female patients (28-64 years: mean 51
      years) with breast cancer. They underwent T2-weighted, dynamic contrast-enhanced
      and diffusion-weighted MR imaging of the breast and axilla using a single-shot
      echo-planar imaging with a b factor of 0500 and 1000 s/mm2. Morphologic and
      quantitative parameters included ADC value of the axillary lymph node which was
      calculated and correlated with surgical findings. RESULTS: The mean ADC value of
      metastatic axillary lymph nodes was 1.08 +/- 0.21 * 10-3 mm2/s and of benign
      lymph nodes was 1.58 +/- 0.14 * 10-3 mm2s. There was statistically difference in
      mean ADC values between metastatic and of benign axillary lymph nodes (P =
      0.001). Metastatic nodes were associated with low ADC <= 1.3 (OR = 8.0), short
      axis/long axis (TS/LS) > 0.6 (OR = 7.0) and absent hilum (OR = 6.21). When ADC of
      1.3 * 10-3 mm2/s was used as a threshold value for differentiating metastatic
      from benign axillary lymph nodes, the best result was obtained with an accuracy
      of 95.6%, sensitivity of 93%, specificity of 100%, positive predictive value of
      100 %, negative predictive value of 87.5 % and area under the curve of 0.974.
      Multivariate model involving combined ADC value and TS/LS improved the diagnostic
      performance of MR imaging with AUC of 1.00. CONCLUSION: We concluded that
      combination of diffusion-weighted MR imaging with morphological and dynamic MR
      imaging findings helps for differentiation of metastatic from benign axillary
      lymph nodes.

PMID- 25763536
TI  - First Mal de Meleda report in Chinese Mainland: two families with a recurrent
      homozygous missense mutation in SLURP-1.

PMID- 25763537
TI  - Multidisciplinary consensus on the classification of antenatal and postnatal
      urinary tract dilation (UTD classification system).

PMID- 25763538
TI  - Clinical utility of fetal autopsy and its impact on genetic counseling.
AB  - OBJECTIVES: We aimed to analyze the utility of fetal autopsy in terms of its
      contribution to establishing a definitive diagnosis and its impact on genetic
      counseling. SUBJECTS AND METHODS: Detailed fetal autopsy was carried out in
      fetuses referred for examination. Clinical utility of fetal autopsy and its
      impact on counseling were measured by adapting previously published parameters.
      RESULTS: We performed autopsy in 230 fetuses. There were 106 cases with single
      system and 92 cases with multisystem involvement. We confirmed prenatal findings
      in 23% of cases and observed additional findings in 37% of cases. In 23% of
      cases, autopsy findings differed enough to change the diagnosis. However, in 17%
      of fetuses, no cause of fetal loss was determined. Risk of recurrence became
      clear in 30.3% of the fetuses, and risk remained the same, but the diagnosis was
      different in 4.8% of cases after autopsy. Hence, autopsy led to refinement of the
      risk of recurrence in 36% of cases. Autopsy aided prenatal counseling of couples
      in 77% of cases by either confirming the prenatal findings (35%) or providing new
      information/ruling out a diagnosis (42%). CONCLUSION: The present study
      quantifies the utility of fetal autopsy in reproductive genetic counseling in a
      large cohort.

PMID- 25763539
TI  - Effect of rice husk gasification residue application on herbicide behavior in
      micro paddy lysimeter.
AB  - Effects of rice husk gasification residues (RHGR) application on the fate of
      herbicides, butachlor and pyrazosulfuron-ethyl, in paddy water were investigated
      using micro paddy lysimeters (MPLs). The dissipation of both herbicides in paddy
      water was faster in the RHGR treated MPL than in the control MPL. The average
      concentrations of butachlor and pyrazosulfuron-ethyl in paddy water in the
      lysimeter treated with RHGR during 21 days were significantly reduced by 51% and
      48%, respectively, as compared to those in the lysimeter without RHGR
      application. The half-lives (DT50) of butachlor in paddy water for control and
      treatment were 3.1 and 2.3 days respectively, and these values of pyrazosulfuron
      ethyl were 3.0 and 2.2 days, respectively. Based on this study, RHGR application
      in rice paddy environment is an alternative method to reduce the concentration of
      herbicide in paddy field water and consequently to reduce potential pollution to
      aquatic environment.

PMID- 25763540
TI  - Clinical outcomes of adult inpatients treated with continuous subcutaneous
      insulin infusion for diabetes mellitus: a systematic review.
AB  - AIMS: To provide a systematic review of the current evidence concerning the
      diabetes-related outcomes of patients provided with continuous subcutaneous
      insulin infusion for treating diabetes mellitus while a hospital inpatient.
      METHODS: Relevant publications were obtained from MEDLINE and EMBASE databases
      concerning hospital inpatients with diabetes being treated with continuous
      subcutaneous insulin infusion. Studies were assessed independently by two
      reviewers, and data on the following outcomes were extracted: inpatient
      mortality; clinical complications, e.g. diabetic ketoacidosis; hyperglycaemia;
      hypoglycaemia; length of hospital stay; mean bedside glucose level; and glucose
      level on discharge. Obstetric cases were examined separately to look at maternal
      and neonatal glycaemic outcomes. RESULTS: A total of 11 studies met the required
      criteria and were analysed in detail, 5 of which were predominantly obstetric. No
      significant complications were reported, with no incidences of death,
      ketoacidosis or severe hypoglycaemia. Length of hospital stay appeared to be
      shorter in those patients who remained on continuous subcutaneous insulin
      infusion, while data on mild hyperglycaemia and hypoglycaemia were inconclusive.
      CONCLUSIONS: There are limited data available to form a significant conclusion
      about the safety of continuous subcutaneous insulin infusion continuation in
      hospital; however, its use can be justified with the presence of a specialized
      inpatient diabetes team for advice and support and an alternative treatment
      regime (e.g. subcutaneous basal bolus) should be accessible if the need were to
      arise.

PMID- 25763541
TI  - Comparative evaluation of a one-pot strategy for the preparation of beta
      cyclodextrin-functionalized monoliths: Effect of the degree of amino substitution
      of beta-cyclodextrin on the column performance.
AB  - To further evaluate the feasibility and applicability of the one-pot strategy in
      monolithic column preparation, two novel beta-cyclodextrin-functionalized organic
      polymeric monoliths were prepared using two beta-cyclodextrin derivatives, i.e.
      mono(6-amino-6-deoxy)-beta-cyclodextrin and heptakis(6-amino-6-deoxy)-beta
      cyclodextrin. In this improved method, mono(6-amino-6-deoxy)-beta-cyclodextrin or
      heptakis(6-amino-6-deoxy)-beta-cyclodextrin reacted with glycidyl methacrylate to
      generate the corresponding functional monomers and were subsequently
      copolymerized with ethylene dimethacrylate. The polymerization conditions for
      both monoliths were carefully optimized to obtain satisfactory column performance
      with respect to column efficiency, reproducibility, permeability, and stability.
      The obtained poly(glycidyl methacrylate-mono(6-amino-6-deoxy)-beta-cyclodextrin
      co-ethylene dimethacrylate) and poly(glycidyl methacrylate-heptakis(6-amino-6
      deoxy)-beta-cyclodextrin-co-ethylene dimethacrylate) monoliths exhibited a
      uniform structure, good permeability, and mechanical stability as indicated by
      scanning electron microscopy and micro-high-performance liquid chromatography
      experimental results. Because of the probable existence of multi-glycidyl
      methacrylate linking spacers on the poly(glycidyl methacrylate-heptakis(6-amino-6
      deoxy)-beta-cyclodextrin-co-ethylene dimethacrylate) monolith, the effect of the
      ratio of glycidyl methacrylate/heptakis(6-amino-6-deoxy)-beta-cyclodextrin was
      especially studied, and satisfactory reproducibility could still be achieved by
      strictly controlling the composition of the polymerization mixture. To
      investigate the effect of the degree of amino substitution of beta-cyclodextrin
      on column performance, a detailed comparison of the two monoliths was also
      carried out using series of analytes including small peptides and chiral acids.
      It was found that the beta-cyclodextrin-functionalized monolith with mono
      glycidyl methacrylate linking spacers demonstrated better chiral separation
      performance than that with multi-glycidyl methacrylate linking spacers. 

PMID- 25763542
TI  - Notch 1 promotes cisplatin-resistant gastric cancer formation by upregulating
      lncRNA AK022798 expression.
AB  - Gastric cancer is now the fourth most common malignancy and the second leading
      cause of death because of cancer. The resistance to anticancer drugs is the main
      cause of chemotherapy failure. In this study, we explored the role of Notch 1 and
      long noncoding RNA (lncRNA) in drug-resistant gastric cancer formation. First, we
      found that Notch 1 was highly expressed in the cisplatin-resistant gastric cancer
      cell lines SGC7901/DDP and BGC823/DDP cells. Then, we constructed a Notch 1
      overexpression vector plasmid; after successful transfection, the SGC7901 and
      BGC823 cells highly expressed Notch 1. Moreover, the expression of multidrug
      resistance-associated protein 1 (MRP1), P-glycoprotein, increased significantly
      and the apoptosis of SGC7901 and BGC823 cells obviously reduced. We further
      screened out the lncRNA AK022798 involved in this process. Furthermore, we used
      siRNA to interfere with lncRNA AK022798 expression, and found that the expression
      of MRP1 and P-glycoprotein decreased significantly in SGC7901/DDP and BGC823/DDP
      cells, and their apoptosis as well as the expressions of caspase 3 and caspase 8
      obviously increased. These results suggest that Notch 1 can promote the lncRNA
      AK022798 expression and result in the formation of SGC7901/DDP and BGC823/DDP
      cells. It may provide a new, useful method for gastric cancer chemotherapy. 

PMID- 25763543
TI  - Trabectedin in advanced synovial sarcomas: a multicenter retrospective study from
      four European institutions and the Italian Rare Cancer Network.
AB  - Treatment options for patients with metastatic synovial sarcoma are limited. Over
      recent years, trabectedin has emerged as an effective agent for patients with
      advanced soft tissue sarcomas resistant to anthracyclines and ifosfamide. The aim
      of this retrospective analysis was to study the efficacy of trabectedin in the
      subgroup of synovial sarcomas. A retrospective analysis was carried out on
      patients with advanced synovial sarcoma treated with trabectedin at four European
      reference sarcoma centers and within the Italian Rare Cancer Network between 2000
      and 2013. Radiological response, progression-free, and overall survival, as well
      as serious and unexpected adverse events were retrospectively assessed. Sixty-one
      patients with metastatic synovial sarcoma were identified. The median number of
      previous chemotherapy regimens was 2 (range 1-6). Nine patients had a partial
      response, in addition to two minor responses, and 19 patients had stable disease,
      for an overall response rate of 15% and a tumor control rate of 50%. The median
      progression-free survival was 3 months, with 23% of patients free from
      progression at 6 months. The median progression-free survival in responding
      patients was 7 months. Trabectedin is a therapeutic option for palliative
      treatment of a subset of patients with metastatic synovial sarcoma. 

PMID- 25763546
TI  - Visual disturbance after bariatric surgery.

PMID- 25763547
TI  - Penetrating ocular fishhook injury.

PMID- 25763548
TI  - Two scleral ectasias in high myopia.

PMID- 25763549
TI  - Enhanced depth imaging-optical coherence tomography of choroidal osteoma.

PMID- 25763550
TI  - Spontaneous active bleeding from normal-appearing iris margin.

PMID- 25763551
TI  - Peripheral retinal ischemia following posttraumatic ocular hypertension in the
      setting of sickle cell trait.

PMID- 25763552
TI  - Acute exudative polymorphous vitelliform maculopathy.

PMID- 25763553
TI  - Bietti crystalline dystrophy in a young woman.

PMID- 25763554
TI  - Oculocutaneous albinism.

PMID- 25763555
TI  - Hematic cyst around orbital floor implant masquerading as choroidal mass.

PMID- 25763556
TI  - Bilateral lens dislocation in a patient with homocystinuria.

PMID- 25763557
TI  - Angiographic-guided treatment of corneal neovascularization.

PMID- 25763559
TI  - Elucidation of direct competition and allosteric modulation of small-molecular
      weight protein ligands using surface plasmon resonance methods.
AB  - The present work introduces a surface plasmon resonance-based method for the
      discrimination of direct competition and allosteric effects that occur in ternary
      systems comprising a receptor protein and two small-molecular-weight ligands that
      bind to it. Fatty acid binding protein 4, fructose-1,6-bisphosphatase and human
      serum albumin were used as model receptor molecules to demonstrate the
      performance of the method. For each of the receptor molecules, pairs of ligand
      molecules were selected for which either direct competition or an allosteric
      effect had already been determined by other methods. The method of discrimination
      introduced here is based on the surface plasmon resonance responses observed at
      equilibrium when an immobilized receptor protein is brought into contact with
      binary mixtures of interacting ligands. These experimentally determined responses
      are compared with the responses calculated using a theoretical model that
      considers both direct competition and allosteric ligand interaction modes. This
      study demonstrates that the allosteric ternary complex model, which enables
      calculation of the fractional occupancy of the protein by each ligand in such
      ternary systems, is well suited for the theoretical calculation of these types of
      responses. For all of the ternary systems considered in this work, the
      experimental and calculated responses in the chosen concentration ratio range
      were identical within a five-sigma confidence interval when the calculations
      considered the correct interaction mode of the ligands (direct competition or
      different types of allosteric regulation), and in case of allosteric modulation,
      also the correct strength of this effect. This study also demonstrates that the
      allosteric ternary complex model-based calculations are well suited to predict
      the ideal concentration ratio range or even single concentration ratios that can
      serve as hot spots for discrimination, and such hot spots can drastically reduce
      the numbers of measurements needed for discrimination between direct competition
      and distinct modulation modes (neutral, positive or negative allostery).

PMID- 25763558
TI  - Public health impact of achieving 80% colorectal cancer screening rates in the
      United States by 2018.
AB  - BACKGROUND: The National Colorectal Cancer Roundtable, a national coalition of
      public, private, and voluntary organizations, has recently announced an
      initiative to increase colorectal cancer (CRC) screening rates in the United
      States to 80% by 2018. The authors evaluated the potential public health benefits
      of achieving this goal. METHODS: The authors simulated the 1980 through 2030
      United States population of individuals aged 50 to 100 years using
      microsimulation modeling. Test-specific historical screening rates were based on
      National Health Interview Survey data for 1987 through 2013. The effects of
      increasing screening rates from approximately 58% in 2013 to 80% in 2018 were
      compared to a scenario in which the screening rate remained approximately
      constant. The outcomes were cancer incidence and mortality rates and numbers of
      CRC cases and deaths during short-term follow-up (2013-2020) and extended follow
      up (2013-2030). RESULTS: Increasing CRC screening rates to 80% by 2018 would
      reduce CRC incidence rates by 17% and mortality rates by 19% during short-term
      follow-up and by 22% and 33%, respectively, during extended follow-up. These
      reductions would amount to a total of 277,000 averted new cancers and 203,000
      averted CRC deaths from 2013 through 2030. CONCLUSIONS: Achieving the goal of
      increasing the uptake of CRC screening in the United States to 80% by 2018 may
      have a considerable public health impact by averting approximately 280,000 new
      cancer cases and 200,000 cancer deaths within <20 years. Cancer 2015;121:2281
      2285. (c) 2015 The Authors. Cancer published by Wiley Periodicals, Inc. on behalf
      of American Cancer Society. This is an open access article under the terms of the
      Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use
      and distribution in any medium, provided the original work is properly cited, the
      use is non-commercial and no modifications or adaptations are made.

PMID- 25763560
TI  - A canine hybrid double-bundle model for study of arthroscopic ACL reconstruction.
AB  - Development and validation of a large animal model for pre-clinical studies of
      intra-articular anterior cruciate ligament (ACL) reconstruction that addresses
      current limitations is highly desirable. The objective of the present study was
      to investigate a translational canine model for ACL reconstruction. With
      institutional approval, adult research hounds underwent arthroscopic debridement
      of the anteromedial bundle (AMB) of the ACL, and then either received a tendon
      autograft for "hybrid double-bundle" ACL reconstruction (n = 12) or no graft to
      remain ACL/AMB-deficient (n = 6). Contralateral knees were used as non-operated
      controls (n = 18) and matched canine cadaveric knees were used as biomechanical
      controls (n = 6). Dogs were assessed using functional, diagnostic imaging, gross,
      biomechanical, and histologic outcome measures required for pre-clinical animal
      models. The data suggest that this canine model was able to overcome the major
      limitations of large animal models used for translational research in ACL
      reconstruction and closely follow clinical aspects of human ACL reconstruction.
      The "hybrid double-bundle" ACL reconstruction allowed for sustained knee function
      without the development of osteoarthritis and for significantly improved
      functional, diagnostic imaging, gross, biomechanical, and histologic outcomes in
      grafted knees compared to ACL/AMB-deficient knees.

PMID- 25763561
TI  - The association between thoracic periaortic fat and major adverse cardiovascular
      events.
AB  - AIM: The study aimed to examine the association between thoracic periaortic fat
      tissue volume and the long-term incidence of major adverse cardiovascular events.
      METHODS: This retrospective cohort study included 433 consecutive patients (372
      male and 61 female). Periaortic fat tissue volume was measured via
      electrocardiogram-gated 64-multidetector computed tomography. The patients were
      evaluated on an average 3 years of follow-up for major adverse cardiovascular
      events. The patients were divided into groups according to the presence of major
      adverse cardiovascular events. RESULTS: Major adverse cardiovascular events were
      noted in 44 (10.2 %) patients during follow-up. Periaortic fat tissue volume was
      significantly higher in the major adverse cardiovascular events (+) group (35.4
      +/- 26.1 cm(3) vs. 24.1 +/- 14.9 cm(3), P = 0.001). The logistic regression model
      showed that periaortic fat tissue volume (hazard ratio: 1.03; 95 % CI: 1.01-1.05;
      P = 0.001), the glomerular filtration rate (hazard ratio: 0.98; 95 % CI: 0.96
      0.99; P = 0.03), and male gender (hazard ratio: 4.76; 95 % CI: 1.08-20.90; P =
      0.04) were independent predictors of major adverse cardiovascular events.
      CONCLUSION: Thoracic periaortic fat tissue volume may be considered a useful new
      parameter for predicting major adverse cardiovascular events.

PMID- 25763562
TI  - Distal tibial fractures: evaluation of different fixation techniques.
AB  - PURPOSE: The purpose of this study was the comparison of the most commonly used
      surgical techniques (external fixation, intramedullary nailing, and plate
      fixation) for the treatment of distal tibial fractures (AO/OTA classification 42
      A, B, C or 43-A, B1). METHODS: A retrospective cohort study of patients who
      underwent surgical treatment for distal tibial fractures between 1992 and 2011
      was performed. RESULTS: A total of 93 patients (52 male/41 female) met inclusion
      criteria. Statistically significant differences were found regarding the
      consolidation time of the intramedullary-nailing (147.32 +/- 91.16 days) and the
      plate-fixation group (135.75 +/- 110.75 days) versus the external-fixation group
      (163.12 +/- 96.79 days; P = 0.001; P = 0.01). Significant differences were also
      observed in the range of motion (ROM) of the ankle joint in the intramedullary
      nailing and plate-fixation group versus the ROM in the external-fixation group (P
      = 0.044; P = 0.025). The overall complication rate was 13/93 (14 %). Out of 66
      patients treated with intramedullary nailing, 8 (12 %) suffered from
      complications. Out of the 15 patients treated with plate and 12 patients with
      external fixation, 2 (13 %) and 3 (25 %) showed complications, respectively.
      CONCLUSION: Our results demonstrate advantages in terms of shorter mobilization
      time and a better ROM of the ankle joint for intramedullary nailing and plate
      fixation compared with external fixation. Due to our results, we suggest internal
      fixation (intramedullary nailing or plate fixation) whenever patient's condition
      and the local fracture situation allow it.

PMID- 25763563
TI  - Increased gut microbiota diversity and abundance of Faecalibacterium prausnitzii
      and Akkermansia after fasting: a pilot study.
AB  - BACKGROUND: An impaired gut microbiota has been reported as an important factor
      in the pathogenesis of obesity. Weight reduction has already been mentioned to
      improve gut microbial subpopulations involved in inflammatory processes, though
      other subpopulations still need further investigation. Thus, weight reduction in
      the context of a fasting program together with a probiotic intervention may
      improve the abundance and diversity of gut microbiota. METHODS: In this pilot
      study, overweight people underwent a fasting program with laxative treatment for
      1 week followed by a 6 week intervention with a probiotic formula. Gut microbiota
      were analyzed on the basis of 16s rDNA with a quantitative real time polymerase
      chain reaction. Additionally, a food frequency questionnaire with questions about
      nutritional behavior, lifestyle, and physical activity was administered before
      and after the intervention. RESULTS: We observed an increase in microbial
      diversity over the study period. No significant changes in abundance of total
      bacteria, or of Bacteroidetes, Prevotella, Clostridium cluster XIVa, or
      Clostridium cluster IV were found, although Faecalibacterium prausnitzii showed
      an increase over the study period. In addition, Akkermanisa and Bifidobacteria
      increased in abundance due to intervention. The inflammation-associated gut
      microbes Enterobacteria and Lactobacilli increased during the first week and then
      declined by the end of the intervention. Two-thirds of the study participants
      harbored Archaea. No significant improvements of eating habits were reported,
      although physical activity improved due to the intervention. CONCLUSIONS: Our
      results show that caloric restriction affects gut microbiota by proliferating
      mucin-degrading microbial subpopulations. An additional intervention with a
      probiotic formula increased probiotic-administered gut microbial populations.

PMID- 25763564
TI  - Progressive left periorbital swelling. Rhabdomyosarcoma.

PMID- 25763565
TI  - Multiple Past Concussions Are Associated with Ongoing Post-Concussive Symptoms
      but Not Cognitive Impairment in Active-Duty Army Soldiers.
AB  - The extent to which multiple past concussions are associated with lingering
      symptoms or mental health problems in military service members is not well
      understood. The purpose of this study was to examine the association between
      lifetime concussion history, cognitive functioning, general health, and
      psychological health in a large sample of fit-for-duty U.S. Army soldiers
      preparing for deployment. Data on 458 active-duty soldiers were collected and
      analyzed. A computerized cognitive screening battery (CNS-Vital Signs((r))) was
      used to assess complex attention (CA), reaction time (RT), processing speed (PS),
      cognitive flexibility (CF), and memory. Health questionnaires included the
      Neurobehavioral Symptom Inventory (NSI), PTSD Checklist-Military Version (PCL-M),
      Zung Depression and Anxiety Scales (ZDS; ZAS), Perceived Stress Scale (PSS),
      Pittsburgh Sleep Quality Index (PSQI), Epworth Sleepiness Scale (ESS), and the
      Alcohol Use and Dependency Identification Test (AUDIT). Soldiers with a history
      of multiple concussions (i.e., three or more concussions) had significantly
      greater post-concussive symptom scores compared with those with zero (d=1.83,
      large effect), one (d=0.64, medium effect), and two (d=0.64, medium effect) prior
      concussions. Although the group with three or more concussions also reported more
      traumatic stress symptoms, the results revealed that traumatic stress was a
      mediator between concussions and post-concussive symptom severity. There were no
      significant differences on neurocognitive testing between the number of
      concussions. These results add to the accumulating evidence suggesting that most
      individuals recover from one or two prior concussions, but there is a greater
      risk for ongoing symptoms if one exceeds this number of injuries. 

PMID- 25763567
TI  - Deoxynivalenol-producing ability of Fusarium culmorum strains and their impact on
      infecting barley in Algeria.
AB  - The cereal-pathogenic Fusarium culmorum (W.G. Smith), causal agent of various
      blights and rot diseases, is considered as a chronic fungus of economic concern
      worldwide including North African countries such as Algeria. This pathogen
      produces a wide range of mycotoxins, amongst which the type B-trichothecene
      deoxynivalenol (DON). In addition to its acute and chronic side effects in
      livestock and humans, DON is believed to play a determinant role in the
      pathogenesis toward Triticeae. However, regardless its significant occurrence and
      impact, little is known about trichothecenes-producing ability of F. culmorum
      infecting cereals in Algeria. The PCR assay based on Tri genes of 12 F. culmorum
      strains (designated Fc1-Fc12), which were recovered from several cropping areas
      of North Algeria, revealed their trichothecenes-producing ability with 3-AcDON
      genotype. The molecular prediction was confirmed by HPLC analysis. All strains
      were able to produce the toxin at detectable levels. Strains Fc1 and Fc12 were
      the highest producers of this mycotoxin with 220 and 230 ug g(-1), respectively.
      The evaluation of pathogenic ability of strains through a barley infesting
      experiment exhibited the significant disease impact of most strains. Significant
      correlation between the DON-producing ability of strains and the increase in both
      disease severity (r = 0.88, P = 0.05) and disease occurrence (r = 0.70, P = 0.05)
      was observed. Chemotyping of F. culmorum isolates and evaluation of their
      pathogenic ability are reported for the first time for isolates from Algeria, and
      highlights the important potential of F. culmorum to contaminate cultivated
      cereal with DON trichothecenes.

PMID- 25763566
TI  - Impact of the F508del mutation on ovine CFTR, a Cl- channel with enhanced
      conductance and ATP-dependent gating.
AB  - KEY POINTS: Malfunction of the cystic fibrosis transmembrane conductance
      regulator (CFTR), a gated pathway for chloride movement, causes the common life
      shortening genetic disease cystic fibrosis (CF). Towards the development of a
      sheep model of CF, we have investigated the function of sheep CFTR. We found that
      sheep CFTR was noticeably more active than human CFTR, while the most common CF
      mutation, F508del, had reduced impact on sheep CFTR function. Our results
      demonstrate that subtle changes in protein structure have marked effects on CFTR
      function and the consequences of the CF mutation F508del. ABSTRACT: Cross-species
      comparative studies are a powerful approach to understanding the epithelial Cl(-)
      channel cystic fibrosis transmembrane conductance regulator (CFTR), which is
      defective in the genetic disease cystic fibrosis (CF). Here, we investigate the
      single-channel behaviour of ovine CFTR and the impact of the most common CF
      mutation, F508del-CFTR, using excised inside-out membrane patches from
      transiently transfected CHO cells. Like human CFTR, ovine CFTR formed a weakly
      inwardly rectifying Cl(-) channel regulated by PKA-dependent phosphorylation,
      inhibited by the open-channel blocker glibenclamide. However, for three reasons,
      ovine CFTR was noticeably more active than human CFTR. First, single-channel
      conductance was increased. Second, open probability was augmented because the
      frequency and duration of channel openings were increased. Third, with enhanced
      affinity and efficacy, ATP more strongly stimulated ovine CFTR channel gating.
      Consistent with these data, the CFTR modulator phloxine B failed to potentiate
      ovine CFTR Cl(-) currents. Similar to its impact on human CFTR, the F508del
      mutation caused a temperature-sensitive folding defect, which disrupted ovine
      CFTR protein processing and reduced membrane stability. However, the F508del
      mutation had reduced impact on ovine CFTR channel gating in contrast to its
      marked effects on human CFTR. We conclude that ovine CFTR forms a regulated Cl(-)
      channel with enhanced conductance and ATP-dependent channel gating. This
      phylogenetic analysis of CFTR structure and function demonstrates that subtle
      changes in structure have pronounced effects on channel function and the
      consequences of the CF mutation F508del.

PMID- 25763568
TI  - Clinical scoring system may improve yield of head CT of non-trauma emergency
      department patients.
AB  - The positive rate of head CT in non-trauma patients presenting to the emergency
      department (ED) is low. Currently, indications for imaging are based on the
      individual experience of the treating physician, which contributes to
      overutilization and variability in imaging utilization. The goals of this study
      are to ascertain the predictors of positive head CT in non-trauma patients and
      demonstrate feasibility of a clinical scoring algorithm to improve yield. We
      retrospectively reviewed 500 consecutive ED non-trauma patients evaluated with
      non-contrast head CT after presenting with headache, altered mentation, syncope,
      dizziness, or focal neurologic deficit. Medical records were assessed for
      clinical risk factors: focal neurologic deficit, altered mental status,
      nausea/vomiting, known malignancy, coagulopathy, and age. Data was analyzed using
      logistic regression and receiver operator characteristic (ROC) curves and three
      derived algorithms. Positive CTs were found in 51 of 500 patients (10.2 %). Only
      two clinical factors were significant: focal neurologic deficit (adjusted odds
      ratio (OR) 20.7; 95 % confidence interval (CI) 9.4-45.7) and age >55 (adjusted OR
      3.08; CI 1.44-6.56). Area under the ROC curve for all three algorithms was 0.73
      0.83. In proposed algorithm C, only patients with focal neurologic deficit (major
      risk factor) or >=2 of the five minor risk factors (altered mental status,
      nausea/vomiting, known malignancy, coagulopathy, and age) would undergo CT
      imaging. This may reduce utilization by 34 % with only a small decrease in
      sensitivity (98 %). Our simple scoring algorithm utilizing multiple clinical risk
      factors could help to predict the non-trauma patients who will benefit from CT
      imaging, resulting in reduced radiation exposure without sacrificing sensitivity.

PMID- 25763569
TI  - Diabetic striatopathy in a patient with hemiballism.
AB  - Diabetic striatopathy is a rare and life-threatening manifestation of diabetes
      mellitus. The disease commonly affects individuals of Asian descent, females, and
      the elderly. Patients usually present with hemiballism-hemichorea caused by
      nonketotic hyperglycemia. Hemiballism-hemichorea is defined as involuntary
      continuous random appearing movement involving one side of the body. This
      movement disorder may develop secondary to stroke, diabetic striatopathy,
      neoplasm, infection, Wilson's disease, and thyrotoxicosis. Despite being rare,
      prompt recognition of a hyperglycemia-induced hemiballism-hemichorea is essential
      because the symptoms are reversible with correction of hyperglycemia. Diagnosis
      is possible based on blood analysis and neuroimaging findings. Laboratory tests
      reveal raised blood glucose and hemoglobin A1C levels which indicate poorly
      controlled diabetes. Neuroimaging provides suggestive findings of diabetic
      striatopathy which are hyperattenuation on computed tomography and hyperintensity
      on T1-weighted magnetic resonance imaging in the basal ganglia. In this case
      report, our aim is to present neuroimaging findings in an adult man with sudden
      onset of hemiballism associated with nonketotic hyperglycemia.

PMID- 25763570
TI  - Congenital malformation of the oval window: experience of radiologic diagnosis
      and surgical technique.
AB  - The aim of this study was to introduce and discuss the method of preoperative
      radiological diagnosis to the congenital absence or atresia of the oval window
      (OW), and the method of surgical treatment. From July 2010 through August 2014,
      patients with normal external canal and tympanic membrane but conductive hearing
      loss underwent high resolution CT scan (HRCT). The multi-planar reformation
      (MPR), a post-processing protocol, was used. The patients with diagnosis of OW
      atresia and malformed stapes preoperatively underwent surgical treatment. The
      vestibular drilled-out and promontory drilled-out technique was used to
      reconstruct the ossicular chain. In the preoperative radiological diagnosis, six
      patients (ears) were noted to have congenital absence or atresia of the oval
      window with malformed facial nerve (class 4) and two patients (ears) were found
      to have footplate fixation (class 2). In the surgical treatment of eight ears,
      the malformed structure was identified and the ossicular chain reconstruction was
      made in six ears. The coronal HRCT CT imaging and the MPR post-processing
      technique can provide us practical and definite information for surgical
      treatment, especially in the discrimination of OW atresia and the fixed stapedal
      footplate. The promontory drill-out technique, fenestration in the bottom of the
      basal turn, provides us a new method in the hearing reconstruction when the area
      of OW was fully covered by malformed facial nerve. This technique was first
      reported in the literature. 

PMID- 25763571
TI  - A prospective investigation of predictive parameters for post-surgical
      recurrences in sinonasal polyposis.
AB  - Even after appropriate surgical therapy, a significant number of patients with
      chronic rhinosinusitis with nasal polyps (CRSwNP) experience recurrences. The end
      point of this prospective study was to apply univariate and multivariate
      statistical models to identify clinical, pathological, and laboratory variables
      that could predict CRSwNP recurrence after endoscopic sinus surgery. The study
      enrolled 143 patients between 2010 and 2013, who were all treated by the same
      surgeon for CRSwNP. Twenty-one patients developed recurrent polyposis. The
      recurrence rate was significantly higher for the eosinophilic than for the non
      eosinophilic type (p = 0.020). Among the patients who developed a recurrence, the
      disease-free interval was significantly shorter for those with eosinophilic-type
      polyposis (p = 0.003). Univariate statistical analysis disclosed significant
      associations between CRSwNP recurrence and age (p = 0.035), allergy (p = 0.014),
      and eosinophilic granulomatosis with polyangiitis (p = 0.01). The multivariate
      model showed that only histological evidence of the eosinophilic type of CRSwNP
      retained an independent prognostic significance in relation to recurrent
      polyposis (p = 0.033). Judging from our results, it is reasonable to consider
      both stricter follow-up protocols and postoperative adjuvant medical treatments
      for patients with a histological diagnosis of eosinophilic-type CRSwNP.

PMID- 25763572
TI  - Investigation of intra-esophageal air kinetics and esophageal sphincters in
      patients with total laryngectomy during esophageal speech.
AB  - The purpose of this study was to evaluate the air kinetics of well- and poor
      speaking patients and their upper (UES) and lower (LES) esophageal sphincter
      pressures . The esophageal speech capability of 23 total laryngectomy patients
      was assessed with the Wepman scale. LES and UES points and pressures were
      measured, and air kinetics were compared. All patients were male, with an average
      age of 58 years. Both the LES and UES pressures were not statistically different
      between good-speaking and poor-speaking patients (p > 0.05). The ability to speak
      was estimated only by looking at tracings. Good speakers are able to retain air
      successfully and on a long-term basis between the upper and lower esophageal
      sphincters. During short and/or rapid speech, these patients are able to rapidly
      suck and then expel the air from their upper esophagus. During long speeches,
      after sucking the air into their distal esophagus, they used the air in the upper
      part of the esophagus during the speech, only later seeming to fill the lower
      esophagus with the air as a possible reserve in the stomach. It has been shown
      that the basic requirement for speaking is the capacity to suck and store the air
      within the esophagus. For successful speech, the air should be stored inside the
      esophagus. MII technology contributes to our understanding of speech kinetics and
      occupies an important place in patient training as a biofeedback technique.

PMID- 25763573
TI  - Proteomics in pharmaceutical research and development.
AB  - In the 20 years since its inception, the evolution of proteomics in
      pharmaceutical industry has mirrored the developments within academia and indeed
      other industries. From initial enthusiasm and subsequent disappointment in global
      protein expression profiling, pharma research saw the biggest impact when
      relating to more focused approaches, such as those exploring the interaction
      between proteins and drugs. Nowadays, proteomics technologies have been
      integrated in many areas of pharmaceutical R&D, ranging from the analysis of
      therapeutic proteins to the monitoring of clinical trials. Here, we review the
      development of proteomics in the drug discovery process, placing it in a
      historical context as well as reviewing the current status in light of the
      contributions to this special issue, which reflect some of the diverse demands of
      the drug and biomarker pipelines. 

PMID- 25763574
TI  - Discordant Regulation of microRNA Between Multiple Experimental Models and Human
      Pulmonary Hypertension.
AB  - BACKGROUND: The dysregulation of microRNA (miRNA) is known to contribute to the
      pathobiology of pulmonary arterial hypertension (PAH). However, the relationships
      between changes in tissue and circulating miRNA levels associated with different
      animal models and human pulmonary hypertension (PH) have not been defined.
      METHODS: A set of miRNAs that have been causally implicated in PH, including miR
      17, -21, -130b, -145, -204, -424, and -503, were measured by reverse
      transcription-quantitative polymerase chain reaction in the plasma, lung, and
      right ventricle of three of the most common rodent models of PH: the rat
      monocrotaline and SU5416 plus chronic hypoxia (SuHx) models and the mouse chronic
      hypoxia model. Plasma miRNA levels were also evaluated in a cohort of patients
      with PAH and healthy subjects. RESULTS: Several miRNA showed PH model-dependent
      perturbations in plasma and tissue levels; however, none of these were conserved
      across all three experimental models. Principle component analysis of miR
      expression changes in plasma revealed distinct clustering between rodent models,
      and SuHx-triggered PH showed the greatest similarity to human PAH. Changes in the
      plasma levels of several miRNA also correlated with changes in tissue expression.
      In particular, miR-424 was concordantly increased (1.3- to 1.5-fold, P < .05) in
      the plasma, lung, and right ventricle of hypoxic mice and in the plasma of
      patients with PAH. CONCLUSIONS: miRNAs with established etiologic roles in PH
      showed context-dependent changes in tissue and circulating levels, which were not
      consistent across rodent models and human PAH. This suggests different miRNA
      dependent mechanisms may contribute to experimental and clinical PH, complicating
      potential diagnostic and therapeutic applications amenable to these miRNAs.

PMID- 25763576
TI  - Utility of surface pollen assemblages to delimit Eastern Eurasian steppe types.
AB  - Modern pollen records have been used to successfully distinguish between specific
      prairie types in North America. Whether the pollen records can be used to detect
      the occurrence of Eurasian steppe, or even to further delimit various steppe
      types was until now unclear. Here we characterized modern pollen assemblages of
      meadow steppe, typical steppe and desert steppe from eastern Eurasia along an
      ecological humidity gradient. The multivariate ordination of the pollen data
      indicated that Eurasian steppe types could be clearly differentiated. The
      different steppe types could be distinguished primarily by xerophilous elements
      in the pollen assemblages. Redundancy analysis indicated that the relative
      abundances of Ephedra, Tamarix, Nitraria and Zygophyllaceae were positively
      correlated with aridity. The relative abundances of Ephedra increased from meadow
      steppe to typical steppe and desert steppe. Tamarix and Zygophyllaceae were found
      in both typical steppe and desert steppe, but not in meadow steppe. Nitraria was
      only found in desert steppe. The relative abundances of xerophilous elements were
      greater in desert steppe than in typical steppe. These findings indicate that
      Eurasian steppe types can be differentiated based on recent pollen rain. 

PMID- 25763575
TI  - Bistability in a metabolic network underpins the de novo evolution of colony
      switching in Pseudomonas fluorescens.
AB  - Phenotype switching is commonly observed in nature. This prevalence has allowed
      the elucidation of a number of underlying molecular mechanisms. However, little
      is known about how phenotypic switches arise and function in their early
      evolutionary stages. The first opportunity to provide empirical insight was
      delivered by an experiment in which populations of the bacterium Pseudomonas
      fluorescens SBW25 evolved, de novo, the ability to switch between two colony
      phenotypes. Here we unravel the molecular mechanism behind colony switching,
      revealing how a single nucleotide change in a gene enmeshed in central metabolism
      (carB) generates such a striking phenotype. We show that colony switching is
      underpinned by ON/OFF expression of capsules consisting of a colanic acid-like
      polymer. We use molecular genetics, biochemical analyses, and experimental
      evolution to establish that capsule switching results from perturbation of the
      pyrimidine biosynthetic pathway. Of central importance is a bifurcation point at
      which uracil triphosphate is partitioned towards either nucleotide metabolism or
      polymer production. This bifurcation marks a cell-fate decision point whereby
      cells with relatively high pyrimidine levels favour nucleotide metabolism
      (capsule OFF), while cells with lower pyrimidine levels divert resources towards
      polymer biosynthesis (capsule ON). This decision point is present and functional
      in the wild-type strain. Finally, we present a simple mathematical model
      demonstrating that the molecular components of the decision point are capable of
      producing switching. Despite its simple mutational cause, the connection between
      genotype and phenotype is complex and multidimensional, offering a rare glimpse
      of how noise in regulatory networks can provide opportunity for evolution. 

PMID- 25763577
TI  - Unprogrammed deworming in the Kibera slum, Nairobi: implications for control of
      soil-transmitted helminthiases.
AB  - BACKGROUND: Programs for control of soil-transmitted helminth (STH) infections
      are increasingly evaluating national mass drug administration (MDA)
      interventions. However, "unprogrammed deworming" (receipt of deworming drugs
      outside of nationally-run STH control programs) occurs frequently. Failure to
      account for these activities may compromise evaluations of MDA effectiveness.
      METHODS: We used a cross-sectional study design to evaluate STH infection and
      unprogrammed deworming among infants (aged 6-11 months), preschool-aged children
      (PSAC, aged 1-4 years), and school-aged children (SAC, aged 5-14 years) in
      Kibera, Kenya, an informal settlement not currently receiving nationally-run MDA
      for STH. STH infection was assessed by triplicate Kato-Katz. We asked heads of
      households with randomly-selected children about past-year receipt and source(s)
      of deworming drugs. Local non-governmental organizations (NGOs) and school staff
      participating in school-based deworming were interviewed to collect information
      on drug coverage. RESULTS: Of 679 children (18 infants, 184 PSAC, and 477 SAC)
      evaluated, 377 (55%) reported receiving at least one unprogrammed deworming
      treatment during the past year. PSAC primarily received treatments from chemists
      (48.3%) or healthcare centers (37.7%); SAC most commonly received treatments at
      school (55.0%). Four NGOs reported past-year deworming activities at 47 of >150
      schools attended by children in our study area. Past-year deworming was
      negatively associated with any-STH infection (34.8% vs 45.4%, p = 0.005). SAC
      whose most recent deworming medication was sourced from a chemist were more often
      infected with Trichuris (38.0%) than those who received their most recent
      treatment from a health center (17.3%) or school (23.1%) (p = 0.05). CONCLUSION:
      Unprogrammed deworming was received by more than half of children in our study
      area, from multiple sources. Both individual-level treatment and unprogrammed
      preventive chemotherapy may serve an important public health function,
      particularly in the absence of programmed deworming; however, they may also lead
      to an overestimation of programmed MDA effectiveness. A standardized, validated
      tool is needed to assess unprogrammed deworming.

PMID- 25763578
TI  - Disruption of IL-21 signaling affects T cell-B cell interactions and abrogates
      protective humoral immunity to malaria.
AB  - Interleukin-21 signaling is important for germinal center B-cell responses,
      isotype switching and generation of memory B cells. However, a role for IL-21 in
      antibody-mediated protection against pathogens has not been demonstrated. Here we
      show that IL-21 is produced by T follicular helper cells and co-expressed with
      IFN-gamma during an erythrocytic-stage malaria infection of Plasmodium chabaudi
      in mice. Mice deficient either in IL-21 or the IL-21 receptor fail to resolve the
      chronic phase of P. chabaudi infection and P. yoelii infection resulting in
      sustained high parasitemias, and are not immune to re-infection. This is
      associated with abrogated P. chabaudi-specific IgG responses, including memory B
      cells. Mixed bone marrow chimeric mice, with T cells carrying a targeted
      disruption of the Il21 gene, or B cells with a targeted disruption of the Il21r
      gene, demonstrate that IL-21 from T cells signaling through the IL-21 receptor on
      B cells is necessary to control chronic P. chabaudi infection. Our data uncover a
      mechanism by which CD4+ T cells and B cells control parasitemia during chronic
      erythrocytic-stage malaria through a single gene, Il21, and demonstrate the
      importance of this cytokine in the control of pathogens by humoral immune
      responses. These data are highly pertinent for designing malaria vaccines
      requiring long-lasting protective B-cell responses. 

PMID- 25763579
TI  - Investigation of occult hepatitis B virus infection in anti-hbc positive patients
      from a liver clinic.
AB  - Occult hepatitis B infection (OBI) is manifested by presence of very low levels
      (<200IU/mL) of Hepatitis B viral DNA (HBV DNA) in the blood and the liver while
      exhibiting undetectable HBV surface antigen (HBsAg). The molecular mechanisms
      underlying this occurrence are still not completely understood. This study
      investigated the prevalence of OBI in a high-risk Australian population and
      compared the HBV S gene sequences of our cohort with reference sequences. Serum
      from HBV DNA positive, HBsAg negative, and hepatitis B core antibody (anti-HBc)
      positive patients (study cohort) were obtained from samples tested at SEALS
      Serology Laboratory using the Abbott Architect, as part of screening and
      diagnostic testing. From a total of 228,108 samples reviewed, 1,451 patients were
      tested for all three OBI markers. Only 10 patients (0.69%) out of the 1,451
      patients were found to fit the selection criteria for OBI. Sequence analysis of
      the HBV S gene from 5 suspected OBI infected patients showed increased sequence
      variability in the 'a' epitope of the major hydrophilic region compared to
      reference sequences. In addition, a total of eight consistent nucleotide
      substitutions resulting in seven amino acid changes were observed, and three
      patients had truncated S gene sequence. These mutations appeared to be stable and
      may result in alterations in HBsAg conformation. These may negatively impact the
      affinity of hepatitis B surface antibody (anti-HBs) and may explain the false
      negative results in serological HBV diagnosis. These changes may also enable the
      virus to persist in the liver by evading immune surveillance. Further studies on
      a bigger cohort are required to determine whether these amino acid variations
      have been acquired in the process of immune escape and serve as markers of OBI. 

PMID- 25763580
TI  - [Point mutations of genes encoding proteins involvedin RNA splicing in patients
      with myelodysplastic syndromes].
AB  - The myelodysplastic syndromes (MDS) constitute heterogeneous group of clonal
      disorders, characterized by ineffective hematopoiesis, peripheral cytopenia and
      increased risk of acute myeloid leukemia development. Molecular mechanisms behind
      MDS have not been fully explained, however recent studies based on new
      technologies confirmed that epigenetic abnormalities and somatic mutation in the
      spliceasome machinery are crucial in pathogenesis of these diseases. Abnormal
      mRNA splicing (excision of intronic sequences from mRNA) has been found in over
      half of all MDS patients and resulted in accumulation of cytogenetical and
      molecular changes. The biological impact of splicing factor genes mutations has
      been evaluated only in a limited extend and current studies concentrate on
      analysis of MDS transcriptome. Molecular characteristic of classical and
      alternative splicing is presented in the paper, according to current knowledge.
      We review the most prominent findings from recent years concerning mutation in
      the spliceasome machinery with respect to MDS phenotype and disease prognosis.
      Perspectives in applying of novel diagnostic and therapeutic possibilities for
      myelodysplasia, based on spliceosome mutations identification are also presented.

PMID- 25763581
TI  - [Evaluation of the effectiveness of exercise-based controlled physical effort in
      women with heart failure in the elderly].
AB  - Heart failure (HF), especially during old age, significantly influences the
      decrease in physical fitness, depriving the patient of their independence during
      everyday life. The positive results of cardiac rehabilitation are one of the most
      well documented methods of lowering the frequency of hospitalisation and
      unfavourable prognosis of cardiovascular diseases. Currently complex cardiac
      rehabilitation is recommended by the American College of Cardiology (ACC) and
      American heart Association (AHA) as being an important element of treating
      patients with HF. However these recommendations are poorly executed in the
      everyday clinical practise, concerning elderly patients. AIM: The aim of study is
      the assessment of the efficacy of controlled physical activity in elderly women,
      in their VII-X decades, with stable cardiac failure, based on exercise training.
      MATERIALS AND METHODS: The study included a group of 55 elderly women (mean age
      84.73 +/- 7.13 tears) with stable heart failure, NYHA II-III. In each patient
      plasma concentration of B-type natriuretic peptide was measured and a 6 minute
      walk test (6MWT) was undertaken. RESULTS: In the study group of patients who
      underwent a 12 weeks of cardiac rehabilitation (72%) a decrease in level of NT
      proBNP was observed after completion of physical training. The mean value
      decreased by 204.7pg/ml. Cardiac rehabilitation resulted in an improvement of
      physical fitness capacity in the group that qualified for fitness training, which
      was observed by an increase in distance covered during the 6MWT, initial distance
      of 236 (+/-127)m to a distance of 300.9 (+/-75.9)m. Furthermore using statistical
      analysis it was shown that in the group qualified for cardiac rehabilitation,
      there is a positive correlation between distance covered during the 6MWT and the
      improvement in clinical symptoms as measured by the NYHA classification, r=0.099,
      p>0.05. CONCLUSIONS: Cardiac rehabilitation modified for the individual needs and
      abilities of the patient is one of the significant elements that make up the
      complex therapy of elderly women with HF. Systematically undertaken physical
      activity occupies an important place in the prevention of cardiovascular
      disorders, by increasing the level of physical fitness, as manifested by the
      increase in distance covered during the 6MWT and by the change in classification
      of NYHA to a higher class or by the decrease in plasma concentration of NT
      proBNP.

PMID- 25763582
TI  - [Patients' knowledge regarding modifiable risk factors of stroke].
AB  - Regular physical activity constitutes effective measure of both primary and
      secondary protection against modern-age diseases. The aim of the paper was to
      assess the level of patients' knowledge regarding the influence of low physical
      activity and other modifiable risk factors affecting the increase in stroke
      occurrence in early stages of rehabilitation (day 9 after the cerebrovascular
      accident). AIM: The aim of the paper was to assess the level of patients'
      knowledge regarding the influence of low physical activity and other modifiable
      risk factors affecting the increase in stroke occurrence in early stages of
      rehabilitation (day 9 after the cerebrovascular accident). MATERIALS AND METHODS:
      The study group included 96 patients hospitalized in the Department of Neurology
      and Epileptology with Stroke Unit, who were diagnosed with a stroke with motion
      deficits and who were recommended kinesitherapy. All patients were interviewed,
      which was complemented with the authors' questionnaire including questions
      regarding the knowledge of modifiable risk factors of stroke. RESULTS: The risk
      factor of stoke which was most frequently mentioned by the patients was arterial
      hypertension - 87 patients (90.6%). Only 7 respondents indicated low physical
      activity. On average, less risk factors were known by women. No correlation
      between age and the number of indicated risk factors was found. CONCLUSIONS:
      Majority of the patients after stroke do not know how important low physical
      activity is in terms of it being a risk factor of stroke. The most recognized
      stroke factors are: arterial hypertension, carotid artery stenosis and atrial
      fibrillation. The level of patients' knowledge regarding modifiable risk factors
      of stroke connected with the style of life is insufficient. It is necessary to
      intensify educational activities that promote physical activity as an important
      element of prevention of modern-age diseases, including stroke.

PMID- 25763583
TI  - [Quality of life assessment in patients with spinal radicular syndromes].
AB  - Spinal radicular syndromes are a serious healthcare issue in the society
      nowadays. A common form of ailments related to the syndromes is sciatica,
      manifesting with severe pain radiating along the course of the sciatic nerve or
      brachialgia manifesting with severe pain perceived from the cervical spine area,
      through the arm and often along the entire upper limb to the fingers. In many
      patients the pain limits the ability to perform daily routine at work and at
      home. AIM: The aim of study was to assess the quality of life in patients with
      radicular pain and its influence on their ability to function in daily life and
      at work. The Quality of Life Index was also determined for physical and mental
      health in the study group. MATERIALS AND METHODS: The study covered 50 patients,
      both male and female (25 women with age average 51 and 25 men with age average
      54) suffering from medically documented spinal radicular syndromes. The Quality
      of life SF-36 questionnaire - Short Form Health Survey was used in the study,
      along with a supplement specifying the study group, with an indication of the
      pain location and the patients' occupations. Additionally, the Roland-Morris
      Disability Questionnaire - RM and the Visual Analogue Scale (VAS) were applied.
      The results were statistically analyzed using descriptive statistics, tests of
      significance of differences between the two populations, covariance analysis, and
      correlation meters. RESULTS: In the female patients suffering from spinal
      radicular syndromes, the pathological process was most commonly located in the
      cervical spine, while in the male patients - in the lumbar spine. The Quality of
      Life index, at a statistically significant level (alpha < 0,05), is higher (hence
      the quality of life is lower) in females suffering from radicular pain. In the
      study group, age was a factor strongly correlated with the intensity of pain -
      the ailment progresses with age. In both groups, exacerbation of the disease
      process associated with spinal radicular syndromes hindered work performance and
      daily routines of the patients. CONCLUSIONS: Ailments associated with spinal
      radicular syndromes affect the quality of life of the female patients studied in
      this research to a greater extent than the male patients, both in terms of mental
      and physical well-being. The intensity of pain associated with spinal radicular
      syndromes progresses with age.

PMID- 25763584
TI  - [Comparison of the effect of laser and magnetic therapy for pain level and the
      range of motion of the spine of people with osteoarthritis lower back].
AB  - Increased expression of degenerative disease of the lumbar spine is an onerous
      task, which reduces the efficiency of the activity and life of many populations.
      It is the most common cause of medical visits. In 95% of cases the cause of
      complaints is a destructive process in the course of degenerative intervertebral
      disc called a lumbar disc herniation. Protrusion of the nucleus pulposus causes
      severe pain and impaired muscle tone, often more chronic and difficult to master.
      Successful treatment of lumbar disc herniation constitutes a serious
      interdisciplinary problem. It is important to properly planned and carried out
      physiotherapy. Based on the number of non-invasive methods, to reduce muscle
      tension, mute pain and alleviation of inflammation. It is the treatment safe,
      effective, and at the same time, which is their big advantage, readily available
      and cheap. It is worth noting that not every method has the same efficiency. The
      question that the methods are effective in relieving pain and helping to
      effectively increase the range of motion led to a comparison of two methods - Low
      Level Laser Therapy (LLLT) and pulsating magnetic field therapy. AIM: The aim of
      the study was to compare the efficacy of LLLT and pulsating magnetic field
      therapy in combating pain and increase range of motion of the spine of people
      with degenerative spine disease of the lower back. MATERIALS AND METHODS: 120
      patients with diagnose lumbar disc herniation whit no nerve roots symptoms.
      Patients were divided into two Groups: A and B. Group A of 60 patients were
      subjected to laser therapy (lambda=820nm, P=400mW, Ed=6-12 J/cm2) and the second
      Group B of 60 patients too, to pulsating magnetic fields procedures (5mT, 30 Hz,
      15 minutes). Every patient before rehabilitation started and right after it has
      finished has undergone examination. Subjective pain assessment was carried out
      using a modified Laitinen questionnaire and Visual Analogue Scale of Pain
      intensity. Spine mobility was evaluated whit the Schober test and the Fingertip
      to-floor-test. The obtained results were subjects to statistical analysis.
      RESULTS: Research shows that both low energy laser and pulsating magnetic field
      physical attributes are effective methods for the treatment of pain and
      restricted mobility of the spine caused by disc herniation. Careful analysis
      emphasizes greater efficiency laser for pain. In contrast, a statistically
      greater improvement in global mobility of the spine, as well as flexion and
      extension of the lumbar recorded in group B, where the applied pulsating magnetic
      field. CONCLUSIONS: Both laser and magnet therapy reduces pain and improves
      mobility of the spine of people with degenerative spine disease of the lower
      back. Comparison of the effectiveness of both methods showed a greater analgesic
      effect of laser treatment, and greater mobility of the spine was observed under
      the influence of pulsating magnetic field therapy.

PMID- 25763585
TI  - [Acute appendicitis masking adenocarcinoma of the cecum].
AB  - Acute appendicitis can be the first symptom of the malignant tumour of the cecum.
      In the article we described case of 76 years old patient who came to the hospital
      on account pain in the right iliac hole, occurrent for 4 days with nausea and
      vomiting. Primarily patient classified to the appendectomy. The ultrasound
      examination showed the pathological mass in projection ileocecal valve and
      appendicitis. The computer tomography of the abdomen confirmed this diagnosis.
      The patient became classified to the right-sides hemicolectomy. The result of
      histopathological examination is adenocarcinoma of the ileocaecal valve and the
      appendicitis phlegmonous. Patient became classified to the adiuvant chemotherapy
      in the regional oncological centre. 

PMID- 25763586
TI  - [The current pharmacotherapy of pulmonary arterial hypertension].
AB  - Pulmonary arterial hypertension (PAH) is a chronic, serious disease caused by
      remodeling of small pulmonary vessels, which leads to increase of pulmonary
      resistance, right heart failure and death. The 1990ths of XX century are the
      beginning of dynamic research into the pathophysiology and treatment of this
      disease. Actually, the goal oriented therapy based on three main metabolic
      pathways includes: prostacyclin's analogues, endothelin receptor antagonists and
      phosphodiesterase-5 inhibitors. Applying this therapy, according to ESC
      guidelines has prolonged significantly the survival in the group of patients with
      PAH. Due to the high cost of the therapy, there has been created the national
      therapeutic program in Poland. It assures the real possibility of therapy for
      patients with PAH from the third FC WHO. 

PMID- 25763587
TI  - [Chronic obstructive pulmonary disease as a risk factor for coronary heart
      disease].
AB  - Chronic obstructive pulmonary disease (COPD) and coronary artery disease (CAD)
      are a significant health problem, not only due to their high incidence, but also
      because of the significant burden of socio - economic. The frequency of illness
      in a population, in both cases increases with age and in people over 70 years of
      age is properly 50% and 75%. Epidemiological data suggest that patients with COPD
      are at increased risk of cardiovascular disease, and impaired lung function is an
      independent risk factor for cardiovascular death. This phenomenon may be related
      to common genetic predisposition and of systemic inflammation for
      atherosclerosis. 

PMID- 25763588
TI  - [Ebola virus disease].
AB  - Ebola virus disease is a zoonosis causing high mortality epidemics in both human
      and animal populations. The virus belongs to the Filoviride family. It is
      composed of a single-strand of RNA. Morbidity foci appear in sub-Saharan Africa.
      The most probable reservoir are fruit bats, which are local delicacy. The most
      common route of infection is via mucosa or damaged skin. The spread of disease is
      rapid due to dietary habits, funeral rites and the insufficient supply of
      disposable equipment in hospitals. The incubation period of the disease ranges
      from 2 to 21 days. The beginning is abrupt, dominated by influenza-like symptoms.
      The disease is staggering with the predominant multi-organ failure and shock.
      Present-day epidemic symptoms from digestive system in the form of vomiting and
      diarrhoea are dominant. Currently, the research on vaccine and experimental drug
      is in progress. The virus is damaged by standard disinfectants used in health
      care units. Epidemic, which broke out in February 2014, caused by the most
      dangerous type Zaire, is the greatest of the existing. Morbidity and mortality is
      underestimated due to numerous unreported cases. 

PMID- 25763589
TI  - [Etiological, epidemiological and clinical aspects of coronavirus infection MERS
      CoV].
AB  - All medical staff and travellers to the Arabian Peninsula should be aware of a
      new epidemic caused by Middle East respiratory syndrome coronavirus (MERS-CoV),
      which has emerged in the Arabian Peninsula (2012), secondary cases have been seen
      in Africa, Europe, Asia and the United States. It seems likely that the outbreak
      will continue with sporadic adventive cases occurring outside the Middle East,
      including Poland. Polish medical literature on MERS-CoV is rather scant.
      Therefore, the article describes etiology, epidemiology, symptoms and diagnostic
      methods of MERS-CoV infection which are available in Poland. Selected cases of
      patients infected with MERS-CoV are also presented followed by preventive
      methods. Comparisons between MERS-CoV and SARS-CoV are briefly described.
      Epidemiological and genetic studies point at zoonotic transmission of MERS-CoV
      from camels and possibly bats. Infection is characterized by severe acute
      respiratory failure with a high fatality rate and the ability to spread from
      person to person; health care-associated outbreaks have been described. No known
      vaccine or antiviral therapy has been developed for MERS. The diagnosis is made
      by demonstrating the MERS-CoV in lower respiratory secretions by RT PCR. General
      hygiene measures such as regular hand washing before and after touching animals
      and avoiding contact with sick animals in the epidemic areas, should be adhered
      to. Health-care workers should always apply standard precautions consistently
      with all patients, regardless of their diagnosis due to non-specific symptoms of
      MERS-CoV in the early stage of infection. 

PMID- 25763590
TI  - [Urinary stress incontinence - one of basic diseases of modern society].
AB  - One of the most common women's chronic diseases is urine incontinence (UI).
      Currently considered to be a social disease of women in all age groups. The
      etiology of urine incontinence is multifactorial and the most common is stress
      urinary incontinence (SUI). UI is a interdisciplinary problem, lying in the
      sphere of interests of different specialties. According to the recommendations of
      the Polish Gynecological Society IU diagnostics can be divided into a preliminary
      stage and specialized stage. Initial diagnosis should start by gathering medical
      history and it can be completed by quality of life questionnaire. Today, one of
      the non-invasive diagnostic methods is the ultrasound study. In a situation where
      diagnosis can not be placed or when surgical treatment is needed, the patient
      should have urodynamic study. Conservative methods and surgery are used in the
      treatment of SUI. Conservative procedure should be the first choice in patients
      with symptoms of IU. Over 200 types of various operations have been described in
      the history of the surgical treatment of SUI. Until now the most common are:
      Burch colposuspension, TVT and TOT and implantation of an artificial sphincter. 

PMID- 25763591
TI  - [Diagnosis of benign ovarian lesions using imaging techniques].
AB  - Benign ovarian focal lesions - such cystic, inflammatory, vascular and
      metaplastic changes - may occur at any age but they are most commonly observed in
      girls at puberty and in young women. The most important preliminary procedures in
      case of suspected adnexal pathologies are interview, physical examination and
      classical female bimanual pelvic examination which together with imaging
      techniques allow correct diagnosis. The commonly available and inexpensive method
      of female reproductive organs imaging is an ultrasonography (USG). Magnetic
      resonance (MR), computed tomography (CT) and in case of malignant lesions also
      positron emission tomography (PET) may also be performed. In doubtful cases, when
      the evaluation of lesions using USG method is difficult MR is recommended. Due to
      high resolution, it facilitates precise evaluation of the type and size of
      lesions, allows distinguishing simple and complex fluid collections while fat
      saturation sequences make it possible to distinguish cysts containing blood and
      fat. Moreover, the patient is not exposed to ionizing radiation, which is
      especially important in women in reproductive age and in children. Computed
      tomography is recommended for preoperative staging and monitoring of treatment of
      malignant adnexal neoplasms as well as localization of small peritoneal
      metastases. 

PMID- 25763592
TI  - Sublethal caspase activation promotes generation of cardiomyocytes from embryonic
      stem cells.
AB  - Generation of new cardiomyocytes is critical for cardiac repair following
      myocardial injury, but which kind of stimuli is most important for cardiomyocyte
      regeneration is still unclear. Here we explore if apoptotic stimuli, manifested
      through caspase activation, influences cardiac progenitor up-regulation and
      cardiomyocyte differentiation. Using mouse embryonic stem cells as a cellular
      model, we show that sublethal activation of caspases increases the yield of
      cardiomyocytes while concurrently promoting the proliferation and differentiation
      of c-Kit+/alpha-actininlow cardiac progenitor cells. A broad-spectrum caspase
      inhibitor blocked these effects. In addition, the caspase inhibitor reversed the
      mRNA expression of genes expressed in cardiomyocytes and their precursors. Our
      study demonstrates that sublethal caspase-activation has an important role in
      cardiomyocyte differentiation and may have significant implications for promoting
      cardiac regeneration after myocardial injury involving exogenous or endogenous
      cell sources. 

PMID- 25763594
TI  - Correction: simultaneous automated screening and confirmatory testing for
      vasculitis-specific ANCA.

PMID- 25763593
TI  - Arachidonic and linoleic acid derivatives impact oocyte ICSI fertilization--a
      prospective analysis of follicular fluid and a matched oocyte in a 'one follicle-
      one retrieved oocyte--one resulting embryo' investigational setting.
AB  - OBJECTIVE: To evaluate human oocyte ability to undergo fertilization and
      subsequent preimplantation embryonic development in relation to a wide panel of
      follicular fluid (FF) arachidonic acid derivatives (AAD) and linoleic acid
      derivatives (LAD) of prospectively selected patients undergoing intracytoplasmic
      sperm injection (ICSI). METHODOLOGY: Study was designed as a two center (a
      university clinic and a private clinic) prospective study. 54 women of 181
      consecutive couples undergoing ICSI were prospectively found to be eligible for
      analysis. 'One follicle - one retrieved oocyte - one resulting embryo' approach
      was used. Each individual follicle was aspirated independently and matched to an
      oocyte growing in this particular follicular milieu. FF samples were assessed for
      AAD and LAD by high-performance liquid chromatography; additionally, activity of
      secretory phospholipase A (sPLA2) was determined by enzyme-linked immunosorbent
      assay. PRINCIPAL FINDINGS: Increased activity of sPLA2 and significantly higher
      AAD and LAD levels were found in FF of oocytes that did not show two pronuclei or
      underwent degeneration after ICSI in comparison to oocytes with the appearance of
      two pronuclei. Receiver operating characteristics curve analysis identified acids
      with the highest sensitivity and specificity: 5oxo-hydroxyeicosatetraenoic, 16
      hydroxyeicosatetraenoic, 9-hydroxyoctadecadieneoic and 12
      hydroxyeicosatetraenoic. No significant differences between AAD and LAD related
      to embryo quality were found. CONCLUSIONS/SIGNIFICANCE: Our study demonstrates
      for the first time that elevated concentrations of AAD and LAD in FF at the time
      of oocyte retrieval significantly decrease the ability of oocytes to form
      pronuclei after ICSI. This may serve as a new tool for non-invasive assessment of
      oocyte developmental capacity. However, levels of AAD and LAD are not associated
      with subsequent embryo quality or pregnancy rate, and therefore more studies are
      needed to determine their usefulness in human IVF procedure.

PMID- 25763595
TI  - Chiral pyrrolidines and piperidines from enantioselective rhodium-catalyzed
      cascade arylative cyclization.
AB  - A new rhodium-catalyzed asymmetric arylative cyclization of nitrogen-tethered
      alkyne-enoate with arylboronic acids is described. In this process two new carbon
      carbon bonds and one stereocenter are formed, providing access to pyrrolidines
      and piperidines with good enantioselectivities by to the use of C1-symmetric
      chiral monosubstituted diene ligands. 

PMID- 25763597
TI  - Accurate hydrogen bond energies within the density functional tight binding
      method.
AB  - The density-functional-based tight-binding (DFTB) approach has been recently
      extended by incorporating one-center exchange-like terms in the expansion of the
      multicenter integrals. This goes beyond the Mulliken approximation and leads to a
      scheme which treats in a self-consistent way the fluctuations of the whole dual
      density matrix and not only its diagonal elements (Mulliken charges). To date,
      only the performance of this new formalism to reproduce excited-state properties
      has been assessed (Dominguez et al. J. Chem. Theory Comput., 2013, 9, 4901-4914).
      Here we study the effect of our corrections on the computation of hydrogen bond
      energies for water clusters and water-containing systems. The limitations of
      traditional DFTB to reproduce hydrogen bonds has been acknowledged often. We
      compare our results for a set of 22 small water clusters and water-containing
      systems as well as for five water hexadecamers to those obtained with the DFTB3
      method. Additionally, we combine our extension with a third-order energy
      expansion in the charge fluctuations. Our results show that the new formalisms
      significantly improve upon original DFTB. 

PMID- 25763599
TI  - Palladium-catalyzed cycloisomerization and aerobic oxidative cycloisomerization
      of homoallenyl amides: a facile and divergent approach to 2-aminofurans.
AB  - A Pd-catalyzed divergent cyclization, including cycloisomerization and aerobic
      oxidative cycloisomerization of homoallenyl amides, is described. Varieties of
      functionalized 2-amino-5-alkylfurans and 2-amino-5-formylfurans can be
      selectively synthesized in good to excellent yields. Preliminary mechanistic
      studies show that peroxide may be a key intermediate for this Pd-catalyzed
      radical aerobic oxidative cycloisomerization of homoallenyl amides. The mild
      reaction conditions, high atom economy, and utilization of air as the oxygen
      source make this protocol very environmentally benign and practical to the
      synthetic community. 

PMID- 25763596
TI  - Electronic and structural elements that regulate the excited-state dynamics in
      purine nucleobase derivatives.
AB  - The excited-state dynamics of the purine free base and 9-methylpurine are
      investigated using experimental and theoretical methods. Femtosecond broadband
      transient absorption experiments reveal that excitation of these purine
      derivatives in aqueous solution at 266 nm results primarily in ultrafast
      conversion of the S2(pipi*) state to the vibrationally excited (1)npi* state.
      Following vibrational and conformational relaxation, the (1)npi* state acts as a
      doorway state in the efficient population of the triplet manifold with an
      intersystem crossing lifetime of hundreds of picoseconds. Experiments show an
      almost 2-fold increase in the intersystem crossing rate on going from polar
      aprotic to nonpolar solvents, suggesting that a solvent-dependent energy barrier
      must be surmounted to access the singlet-to-triplet crossing region. Ab initio
      static and surface-hopping dynamics simulations lend strong support to the
      proposed relaxation mechanism. Collectively, the experimental and computational
      results demonstrate that the accessibility of the npi* states and the topology of
      the potential energy surfaces in the vicinity of conical intersections are key
      elements in controlling the excited-state dynamics of the purine derivatives.
      From a structural perspective, it is shown that the purine chromophore is not
      responsible for the ultrafast internal conversion in the adenine and guanine
      monomers. Instead, C6 functionalization plays an important role in regulating the
      rates of radiative and nonradiative relaxation. C6 functionalization inhibits
      access to the (1)npi* state while simultaneously facilitating access to the
      (1)pipi*(La)/S0 conical intersection, such that population of the (1)npi* state
      cannot compete with the relaxation pathways to the ground state involving ring
      puckering at the C2 position. 

PMID- 25763598
TI  - Tropospheric halogen chemistry: sources, cycling, and impacts.

PMID- 25763600
TI  - Combination of precolumn nitro-reduction and ultraperformance liquid
      chromatography with fluorescence detection for the sensitive quantification of 1
      nitronaphthalene, 2-nitrofluorene, and 1-nitropyrene in meat products.
AB  - Carcinogenic nitropolycyclic aromatic hydrocarbons (nitro-PAHs) are ubiquitous in
      the ambient environment. They are emitted predominantly from internal combustion
      engines and by reacting polycyclic aromatic hydrocarbons with nitrogen oxide. The
      emerging evidence that nitro-PAHs are taken up by plants and bioaccumulatd in the
      food chain has aroused worldwide concerns for the potential of chronic poisoning
      through dietary intake. Therefore, analytical methods of high sensitivity are
      extremely important for assessing the risk of human exposure to nitro-PAHs. This
      paper describes the development of a simple and robust ultraperformance liquid
      chromatography coupled fluorescence detector (UPLC-FLD) method for the sensitive
      determination of nitro-PAHs in meat products. The method entails precolumn
      reduction of the otherwise nonfluorescent nitro-PAHs to amino-PAHs which strongly
      fluoresce for their determination by UPLC-FLD analysis. The developed method was
      validated for extraction efficiency, accuracy, precision, and detection limit and
      has been successfully applied in quantifying 1-nitronaphthalene (1-NN), 2
      nitrofluorene (2-NF), and 1-nitropyrene (1-NP) in fresh and cured meat products.
      The results showed that the combination of Fe/H(+)-induced nitro-reduction and
      UPLC-FLD analysis allows sensitive quantification of 1-NN, 2-NF, and 1-NP at
      detection limits of 0.59, 0.51, and 0.31 MUg/kg, respectively, which is at least
      10 times lower than those of the existing analytical methods.

PMID- 25763601
TI  - Intramolecular cyclopropanation and C-H insertion reactions with metal carbenoids
      generated from cyclopropenes.
AB  - Activation of unsaturated carbon-carbon bonds by means of transition metal
      catalysts is an exceptionally active research field in organic synthesis. In this
      context, due to their high ring strain, cyclopropenes constitute an interesting
      class of substrates that displays a versatile reactivity in the presence of
      transition metal catalysts. Metal complexes of vinyl carbenes are involved as key
      intermediates in a wide variety of transition metal-catalyzed ring-opening
      reactions of cyclopropenes. Most of the reported transformations rely on
      intermolecular or intramolecular addition of nucleophiles to these latter
      reactive species. This Account focuses specifically on the reactivity of
      carbenoids resulting from the ring-opening of cyclopropenes in cyclopropanation
      and C-H insertion reactions, which are arguably two of the most representative
      transformations of metal complexes of carbenes. Compared with the more
      conventional alpha-diazo carbonyl compounds, the use of cyclopropenes as
      precursors of metal carbenoids in intramolecular cyclopropanation or C-H
      insertion reactions has been largely underexploited. One of the challenges is to
      devise appropriately substituted and readily available cyclopropenes that would
      not only undergo regioselective ring-opening under mild conditions but also
      trigger the subsequent desired transformations with a high level of
      chemoselectivity and stereoselectivity. These goals were met by considering
      several substrates derived from the readily available 3,3
      dimethylcyclopropenylcarbinols or 3,3-dimethylcyclopropenylcarbinyl amines. In
      the case of 1,6-cyclopropene-enes, highly efficient and diastereoselective
      gold(I)-catalyzed ring-opening/intramolecular cyclopropanations were developed as
      a route to diversely substituted heterocycles and carbocycles possessing a
      bicyclo[4.1.0]heptane framework. The use of rhodium(II) catalysts enabled us to
      widen the scope of this transformation for the synthesis of medium-sized
      heterocyclic scaffolds incorporating an eight-membered ring. The reactivity of
      rhodium(II) carbenoids generated from 3,3-dimethylcyclopropenylcarbinols was also
      investigated in intramolecular C(sp(3))-H insertions. Despite their low
      electrophilic character, these purely donor rhodium(II) carbenoids underwent
      remarkably efficient diastereoselective 1,5- or 1,6-C-H insertions allowing
      access to a wide variety of substituted cyclopentanols, cyclohexanols,
      bicycloalkanols, and tetrahydropyrans with high level of diastereoselectivity and
      with complete tolerance of a free hydroxyl group. The products arising from the
      gold(I)- or rhodium(II)-catalyzed ring-opening/intramolecular cyclopropanation or
      C-H insertion of 3,3-dimethylcyclopropenylcarbinols or 3,3
      dimethylcyclopropenylcarbinyl amines always incorporate an isopropylidene moiety,
      which can potentially undergo subsequent oxidative cleavage into a carbonyl group
      without epimerization. By virtue of this operation, the 3,3-dimethylcyclopropenyl
      group formally behaves as a valuable surrogate for an alpha-diazoketone, with
      obvious advantages considering the ease of access to the corresponding substrates
      and that no hazardous reagents are involved in their preparation. These studies
      have set a useful basis for the development of other reaction pathways involving
      metal carbenoids generated from these readily available families of substituted
      cyclopropenes, including the investigation of the yet underexploited synthetic
      potential of purely donor rhodium(II) carbenoids. 

PMID- 25763602
TI  - Antimicrobial Phenolic Bisabolanes and Related Derivatives from Penicillium
      aculeatum SD-321, a Deep Sea Sediment-Derived Fungus.
AB  - Three new phenolic bisabolane sesquiterpenes, peniciaculins A (1) and B (2) and
      (7S)-(-)-10-hydroxysydonic acid (3), together with a new nor-bisabolane
      derivative, 1-hydroxyboivinianin A (4), as well as six known bisabolanes (5-10),
      were identified from the culture of Penicillium aculeatum SD-321, a fungus
      isolated from deep-sea sediments. The structures of these compounds were mainly
      determined by analysis of spectroscopic data, and the absolute configurations of
      compounds 1-4 were established by comparing their ECD spectra with those of known
      analogues or by TDDFT-ECD calculations. Compound 1 represents the first example
      of a bisabolane analogue linked to a diphenyl ether moiety via an ether bond,
      while compound 2 appears to be the first dimeric bisabolane analogue where the
      two monomers are coupled to each other via an ester bond. The isolated compounds
      were evaluated for antimicrobial activity against 10 human and aquatic pathogenic
      bacteria and three plant-pathogenic fungi. 

PMID- 25763603
TI  - Visible light caffeic acid degradation by carbon-doped titanium dioxide.
AB  - The removal of the phenolic compound, caffeic acid, by photodegradation has been
      investigated using carbon-doped titanium dioxide particles as a photocatalyst
      under visible light. UV-vis absorption spectroscopy and gas chromatography-ion
      trap mass spectrometry analyses revealed a substrate concentration dependence of
      the removal of caffeic acid from a water solution. The k2 and t(0.5) parameters
      of each reaction were calculated by fitting kinetics data to a second-order
      kinetic adsorption model. To evaluate the photodegradation event, the effect of
      the adsorption process on the whole degradation was also monitored in the absence
      of light. Adsorption isotherm studies supported by zeta potential and scanning
      electron microscopy data demonstrated the pivotal role of the absorption
      mechanism. It was found that the whole photodegradation process is governed by a
      synergic mechanism in which adsorption and photodegradation are involved. This
      study, centered on the removal of caffeic acid from aqueous solutions, highlights
      the potential application of this technology for the elimination of phenolic
      compounds from olive mill wastewater, a fundamental goal in both the agronomical
      and environmental fields.

PMID- 25763604
TI  - Quantifying Impact of Chromosome Copy Number on Recombination in Escherichia
      coli.
AB  - The ability to precisely and efficiently recombineer synthetic DNA into organisms
      of interest in a quantitative manner is a key requirement in genome engineering.
      Even though considerable effort has gone into the characterization of
      recombination in Escherichia coli, there is still substantial variability in
      reported recombination efficiencies. We hypothesized that this observed
      variability could, in part, be explained by the variability in chromosome copy
      number as well as the location of the replication forks relative to the
      recombination site. During rapid growth, E. coli cells may contain several pairs
      of open replication forks. While recombineered forks are resolving and
      segregating within the population, changes in apparent recombineering efficiency
      should be observed. In the case of dominant phenotypes, we predicted and then
      experimentally confirmed that the apparent recombination efficiency declined
      during recovery until complete segregation of recombineered and wild-type genomes
      had occurred. We observed the reverse trend for recessive phenotypes. The
      observed changes in apparent recombination efficiency were found to be in
      agreement with mathematical calculations based on our proposed mechanism. We also
      provide a model that can be used to estimate the total segregated recombination
      efficiency based on an initial efficiency and growth rate. These results
      emphasize the importance of employing quantitative strategies in the design of
      genome-scale engineering efforts. 

PMID- 25763606
TI  - TOA02, a recombinant adenovirus with tumor-specific granulocyte macrophage colony
      stimulating factor expression, has limited biodistribution and low toxicity in
      rhesus monkeys.
AB  - TOA02 is a genetically modified oncolytic adenovirus that contains human
      granulocyte macrophage colony-stimulating factor (hGM-CSF). It has been verified
      in vitro that TOA02 can specifically replicate in tumor cells that possess high
      telomerase reverse transcriptase activity and Rb pathway deficiency. However, the
      replication specificity, hGM-CSF expression, and toxicity of TOA02 in vivo are
      still unknown. Therefore, the biosafety of TOA02 remains a critical issue before
      its potential clinical use. In this study, viral replication and hGM-CSF
      expression levels were investigated in both xenograft nude mouse models and
      rhesus monkeys, and chronic toxicity was evaluated in rhesus monkeys. Our results
      show that (1) the replication and hGM-CSF expression of TOA02 are high in tumor
      model, (2) there are no hGM-CSF expression and continuous viral replication in
      rhesus monkeys except in pancreas and epididymis, and (3) the antiadenovirus
      antibody was positive in the chronic toxicity experiment, but pathological change
      of blood cytology and blood biochemistry were not found. There were no other
      histopathology lesions apart from skin inflammation of the administration region,
      lymphadenitis of draining lymph nodes. Our findings suggest that TOA02 is
      relatively safe for in vivo application, thus laying the foundation for future
      clinical trials with TOA02. 

PMID- 25763605
TI  - Noninvasive analysis of the sputum transcriptome discriminates clinical
      phenotypes of asthma.
AB  - RATIONALE: The airway transcriptome includes genes that contribute to the
      pathophysiologic heterogeneity seen in individuals with asthma. OBJECTIVES: We
      analyzed sputum gene expression for transcriptomic endotypes of asthma (TEA),
      gene signatures that discriminate phenotypes of disease. METHODS: Gene expression
      in the sputum and blood of patients with asthma was measured using Affymetrix
      microarrays. Unsupervised clustering analysis based on pathways from the Kyoto
      Encyclopedia of Genes and Genomes was used to identify TEA clusters. Logistic
      regression analysis of matched blood samples defined an expression profile in the
      circulation to determine the TEA cluster assignment in a cohort of children with
      asthma to replicate clinical phenotypes. MEASUREMENTS AND MAIN RESULTS: Three TEA
      clusters were identified. TEA cluster 1 had the most subjects with a history of
      intubation (P = 0.05), a lower prebronchodilator FEV1 (P = 0.006), a higher
      bronchodilator response (P = 0.03), and higher exhaled nitric oxide levels (P =
      0.04) compared with the other TEA clusters. TEA cluster 2, the smallest cluster,
      had the most subjects that were hospitalized for asthma (P = 0.04). TEA cluster
      3, the largest cluster, had normal lung function, low exhaled nitric oxide
      levels, and lower inhaled steroid requirements. Evaluation of TEA clusters in
      children confirmed that TEA clusters 1 and 2 are associated with a history of
      intubation (P = 5.58 * 10(-6)) and hospitalization (P = 0.01), respectively.
      CONCLUSIONS: There are common patterns of gene expression in the sputum and blood
      of children and adults that are associated with near-fatal, severe, and milder
      asthma.

PMID- 25763607
TI  - Paradoxical dissociation between hepatic fat content and de novo lipogenesis due
      to PNPLA3 sequence variant.
AB  - CONTEXT: Nonalcoholic fatty liver disease (NAFLD) is an emerging epidemic disease
      characterized by increased hepatic fat, due to an imbalance between synthesis and
      removal of hepatic lipids. In particular, increased hepatic de novo lipogenesis
      (DNL) is a key feature associated with NAFLD. The genetic variations I148M in
      PNPLA3 and E167K in TM6SF2 confer susceptibility to NAFLD. OBJECTIVE: Here we
      aimed to investigate the contribution of DNL to liver fat accumulation in the
      PNPLA3 I148M or TM6SF2 E167K genetic determinants of NAFLD. PATIENTS AND METHODS:
      The PNPLA3 I148M and TM6SF2 E167K were genotyped in two well-characterized
      cohorts of Europeans. In the first cohort (Helsinki cohort; n = 88), we directly
      quantified hepatic DNL using deuterated water. In the second cohort (Milan
      cohort; n = 63), we quantified the hepatic expression of SREBP1c that we have
      found previously associated with increased fat content. Liver fat was measured by
      magnetic resonance proton spectroscopy in the Helsinki cohort, and by
      histological assessment of liver biopsies in the Milan cohort. RESULTS: PNPLA3
      148M was associated with lower DNL and expression of the lipogenic transcription
      factor SREBP1c despite substantial increased hepatic fat content. CONCLUSIONS:
      Our data show a paradoxical dissociation between hepatic DNL and hepatic fat
      content due to the PNPLA3 148M allele indicating that increased DNL is not a key
      feature in all individuals with hepatic steatosis, and reinforces the
      contribution of decreased mobilization of hepatic triglycerides for hepatic lipid
      accumulation in subject with the PNPLA3 148M allele.

PMID- 25763608
TI  - Frequency and clinical correlates of somatic Ying Yang 1 mutations in sporadic
      insulinomas.
AB  - CONTEXT: Insulinomas represent pancreatic neuroendocrine neoplasms that cause
      severe morbidity attributed to their often pronounced endocrine activity. Apart
      from hereditary forms such as multiple endocrine neoplasia type 1 (MEN-1),
      genetic causes for sporadic insulinoma development had remained obscure until
      recently. Applying next-generation sequencing methods, disease-causing genetic
      alterations have been identified in various endocrine tumors. OBJECTIVE AND
      DESIGN: Paired tumor and blood DNA from eight patients with sporadic insulinomas
      (five females and two malignant tumors) were analyzed by whole-exome sequencing.
      After this initial analysis, Ying Yang 1 (YY1) mutation status was assessed in a
      larger cohort of 39 additional insulinomas (including eight malignant and one
      liver metastasis) from three German hospitals by targeted sequencing. The
      mutation status was correlated with various clinical parameters. RESULTS: A range
      of one to 12 somatic genetic variants were identified by exome sequencing. A
      recurrent somatic Thr372Arg YY1 point mutation was detected in two patients of
      the initial cohort and four patients of the second cohort (total, six of 47;
      13%). The presence of the mutation was associated with a trend toward higher age
      (63.5 y; IQR, 48.0-74.0 vs 45.0 y; IQR, 33.0-63.0; P = .05), and all affected
      patients were females (six of six; P = .04). All other clinical parameters,
      including the presence of malignancy and metastatic spread, tumor localization,
      and hypoglycemic episodes were not different between YY1-mutated and nonmutated
      tumor carriers. CONCLUSIONS: The somatic Thr372Arg YY1 mutation is a relevant
      finding in female patients with sporadic insulinomas. The prevalence of this
      mutation in this Caucasian population is considerably lower compared to that of a
      recently described Asian cohort.

PMID- 25763609
TI  - Selective coregulator function and restriction of steroid receptor chromatin
      occupancy by Hic-5.
AB  - Steroid receptors (SRs) bind specific DNA regulatory sequences, thereby
      activating and repressing gene expression. We previously showed that
      transcriptional coregulator Hic-5 facilitates glucocorticoid regulation of some
      genes but blocks glucocorticoid regulation of others. Here, in a genome-wide
      analysis, Hic-5 depletion dramatically increased the global number of sites
      occupied by glucocorticoid receptor (GR) alpha (the major GR isoform), and many
      binding sites blocked by Hic-5 were associated with genes for which Hic-5 also
      blocked glucocorticoid-regulated expression. Hic-5 had similar effects on GRgamma
      (a splice variant of GRalpha) and estrogen receptor alpha (ERalpha), facilitating
      hormonal regulation of some genes and blocking hormonal regulation of others. As
      with GRalpha, Hic-5 blocking of hormonal gene regulation mediated by GRgamma and
      ERalpha was associated with blocking of GRgamma and ERalpha occupancy at nearby
      sites. Hic-5 supported hormonal regulation of many more genes for GRalpha than
      for GRgamma or ERalpha and thus exhibited selective coregulator functions for
      different SRs. In contrast, the number of Hic-5-blocked genes was similar for all
      3 SRs. In addition to classic coregulator activity, Hic-5 influences the genomic
      occupancy of multiple SRs and thereby blocks some aspects of hormonal regulation.
      Thus, Hic-5, because of its tissue-specific expression, could contribute to
      tissue-specific genomic occupancy and gene regulation by SRs. 

PMID- 25763610
TI  - Mitogen-Activated Protein Kinase 8 (MAP3K8) Mediates the Signaling Pathway of
      Estradiol Stimulating Progesterone Production Through G Protein-Coupled Receptor
      30 (GPR30) in Mouse Corpus Luteum.
AB  - The corpus luteum (CL) is a transient endocrine gland developed from the ovulated
      follicles, and the most important function is to synthesize and secrete
      progesterone (P(4)), a key hormone to maintain normal pregnancy and estrous cycle
      in most mammals. It is known that estrogen has a vital role in stimulating P(4)
      synthesis in CL, but it still remains unclear about the mechanism of estradiol
      (E(2)) regulating P(4) production in CL. Our results here first show that all of
      the CL cells express MAPK 8 (MAP3K8), and the MAP3K8 level is much higher at the
      midstage than at the early and late stages during CL development. The further
      functional studies show that the forced inhibition of endogenous MAP3K8 by using
      MAP3K8 small interfering RNA and MAP3K8 signaling inhibitor (MAP3K8i) in the
      luteal cells significantly block the P(4) synthesis and neutralize the enhancing
      effect of E(2) on P(4) production in the CL. In addition, our results here
      demonstrate that the stimulating effect of E(2) on P(4) synthesis relies on the
      estrogen no-classical protein-coupled receptor 30, and MAP3K8 is involved in
      mediating the protein-coupled receptor 30signaling of E(2) affecting P(4)
      synthesis via stimulating ERK phosphorylation. These novel findings are critical
      for our understanding the ovary physiology and pathological mechanism.

PMID- 25763612
TI  - Calcium mobilizations in response to changes in the gravity vector in Arabidopsis
      seedlings: possible cellular mechanisms.
AB  - Gravity influences the growth direction of higher plants. Changes in the gravity
      vector (gravistimulation) immediately promote the increase in the cytoplasmic
      free calcium ion concentration ([Ca(2+)]c) in Arabidopsis (Arabidopsis thaliana)
      seedlings. When the seedlings are gravistimulated by reorientation at 180 degrees
      , a transient two peaked (biphasic) [Ca(2+)]c-increase arises in their hypocotyl
      and petioles. Parabolic flights (PFs) can generate a variety of gravity-stimuli,
      and enables us to measure gravity-induced [Ca(2+)]c-increases without specimen
      rotation, which demonstrate that Arabidopsis seedlings possess a rapid gravity
      sensing mechanism linearly transducing a wide range of gravitational changes into
      Ca(2+) signals on a sub-second timescale. Hypergravity by centrifugation (20 g or
      300 g) also induces similar transient [Ca(2+)]c-increases. In this review, we
      propose models for possible cellular processes of the garavi-stimulus-induced
      [Ca(2+)]c-increase, and evaluate those by examining whether the model fits well
      with the kinetic parameters derived from the [Ca(2+)]c-increases obtained by
      applying gravistimulus with different amplitudes and time sequences. 

PMID- 25763611
TI  - Minireview: the impact of antenatal therapeutic synthetic glucocorticoids on the
      developing fetal brain.
AB  - The life-threatening, emotional, and economic burdens of premature birth have
      been greatly alleviated by antenatal glucocorticoid (GC) treatment. Antenatal GCs
      accelerate tissue development reducing respiratory distress syndrome and
      intraventricular hemorrhage in premature infants. However, they can also alter
      developmental processes in the brain and trigger adverse behavioral and metabolic
      outcomes later in life. This review summarizes animal model and clinical studies
      that examined the impact of antenatal GCs on the developing brain. In addition,
      we describe studies that assess glucocorticoid receptor (GR) action in neural
      stem/progenitor cells (NSPCs) in vivo and in vitro. We highlight recent work from
      our group on two GR pathways that impact NSPC proliferation, ie, a nongenomic GR
      pathway that regulates gap junction intercellular communication between coupled
      NSPCs through site-specific phosphorylation of connexin 43 and a genomic pathway
      driven by differential promoter recruitment of a specific GR phosphoisoform. 

PMID- 25763613
TI  - Memristors in the Venus flytrap.
AB  - A memristor is a nonlinear element because its current-voltage characteristic is
      similar to that of a Lissajous pattern for nonlinear systems. We investigated the
      possible presence of memristors in the electrical circuitry of the Venus
      flytrap's upper and lower leaves. The electrostimulation of this plant by bipolar
      sinusoidal or triangle periodic waves induces electrical responses in the upper
      and lower leaves of the Venus flytrap with fingerprints of memristors. The
      analysis was based on cyclic voltammetric characteristics where the memristor, a
      resistor with memory, should manifest itself. Tetraethylammonium chloride, an
      inhibitor of voltage gated K(+) channels, or NPPB, a blocker of voltage gated Cl(
      ) and K(+) channels, transform a memristor to a resistor in plant tissue.
      Uncouplers carbonylcyanide-3-chlorophenylhydrazone (CCCP) and carbonylcyanide-4
      trifluoromethoxy-phenyl hydrazone (FCCP) decrease the amplitude of electrical
      responses at low and high frequencies of bipolar periodic electrostimulating
      waves. Our results demonstrate that voltage gated K(+) channels in the Venus
      flytrap have properties of memristors of type 1 and type 2. The discovery of
      memristors in plants creates a new direction in the modeling and understanding of
      electrical phenomena in plants. 

PMID- 25763614
TI  - Proteomic profiling of gamma-ECS overexpressed transgenic Nicotiana in response
      to drought stress.
AB  - The contribution of Glutathione (GSH) in drought stress tolerance is an
      established fact. However, the proteins which are directly or indirectly related
      to the increased level of GSH in response to drought stress are yet to be known.
      To explore this, here, transgenic tobacco plants (NtGp11) overexpressing gamma
      glutamylcysteine synthetase (gamma-ECS) was tested for tolerance against drought
      stress. NtGp11 conferred tolerance to drought stress by increased germination
      rate, water retention, water recovery, chlorophyll, and proline content compared
      with wild-type plants. Semi-quantitative RT-PCR analysis revealed that the
      transcript levels of stress-responsive genes were higher in NtGp11 compared with
      wild-type in response to drought stress. Two-dimensional gel electrophoresis (2
      DE) coupled with MALDI TOF-TOF MS/MS analysis has been used to identify 43
      differentially expressed proteins in response to drought in wild-type and NtGp11
      plants. The results demonstrated the up-accumulation of 58.1% of proteins among
      which 36%, 24%, and 20% of them were related to stress and defense, carbon
      metabolism and energy metabolism categories, respectively. Taken together, our
      results demonstrated that GSH plays an important role in combating drought stress
      in plants by inducing stress related genes and proteins like HSP70, chalcone
      synthase, glutathione peroxidase, thioredoxin peroxidase, ACC oxidase, and heme
      oxygenase I. 

PMID- 25763615
TI  - Light-sensitive Phytochrome-Interacting Factors (PIFs) are not required to
      regulate phytoene synthase gene expression in the root.
AB  - Carotenoids are plastidial isoprenoids essential for the protection of
      photosynthetic tissues against excess light. They also serve as precursors of
      apocarotenoid hormones such as abscisic acid (ABA) and strigolactones. The first
      enzyme of the carotenoid pathway, phytoene synthase (PSY), is also the main rate
      limiting step. Unlike that observed in most plants, PSY is encoded by a single
      gene in Arabidopsis thaliana. Whereas the PSY gene is induced by light in
      photosynthetic tissues, a root-specific upregulation of PSY expression by salt
      stress and ABA has been recently demonstrated. Here we report that transcription
      factors of the Phytochrome-Interacting Factor (PIF) family, previously shown to
      repress PSY expression in etiolated seedlings and mature leaves, do not influence
      PSY expression in roots. Together, our results suggest that organ-specific
      pathways regulate PSY expression and hence carotenoid production in response to
      different environmental cues. 

PMID- 25763616
TI  - Superoxide and its metabolism during germination and axis growth of Vigna radiata
      (L.) Wilczek seeds.
AB  - Involvement of reactive oxygen species in regulation of plant growth and
      development is recently being demonstrated with various results depending on the
      experimental system and plant species. Role of superoxide and its metabolism in
      germination and axis growth was investigated in case of Vigna radiata seeds, a
      non-endospermous leguminous species having epigeal germination, by studying the
      effect of different reactive oxygen species (ROS) inhibitors, distribution of
      O2(*)- and H2O2 and ROS enzyme profile in axes. Germination percentage and axis
      growth were determined under treatment with ROS inhibitors and scavengers.
      Localization of O2(*)- and H2O2 was done using nitroblue tetrazolium (NBT) and
      3,3',5,5'-tetramethyl benzidine dihydrochloride hydrate (TMB), respectively.
      Apoplastic level of O2(*)- was monitored by spectrophotometric analysis of
      bathing medium of axes. Profiles of NADPH oxidase and superoxide dismutase (SOD)
      were studied by in-gel assay. Germination was retarded by treatments affecting
      ROS level except H2O2 scavengers, while axis growth was retarded by all.
      Superoxide synthesis inhibitor and scavenger prevented H2O2 accumulation in axes
      in later phase as revealed from TMB staining. Activity of Cu/Zn SOD1 was
      initially high and declined thereafter. Superoxide being produced in apoplast
      possibly by NADPH oxidase activity is further metabolized to (*)OH via H2O2.
      Germination process depends possibly on (*)OH production in the axes. Post
      germinative axis growth requires O2(*)- while the differentiating zone of axis
      (radicle) requires H2O2 for cell wall stiffening. 

PMID- 25763617
TI  - Organelle import of proteins with dual targeting properties into mitochondria and
      chloroplasts takes place by the general import pathways.
AB  - As a consequence of the endosymbiotic gene transfer, most mitochondrial and
      chloroplastic proteins are nuclear encoded and synthesized in the cytosol as
      precursor proteins with transit peptides mediating transport to their subcellular
      destination. It is often assumed that these transit peptides are strictly
      monospecific for a single organelle. But in recent years more and more proteins
      have been identified which carry transit peptides that are capable of mediating
      transport into both mitochondria and chloroplasts. In a recent study we showed
      with a combination of in silico, in organello, and in vivo approaches that the
      frequency of such proteins is apparently much higher than usually anticipated.(1)
      Here we demonstrate with in organello competition experiments that the import of
      2 of these dually targeted proteins (GrpE and EF-Tu) takes place by the same
      import pathways that are used by organelle proteins with "typical" monospecific
      targeting properties. 

PMID- 25763618
TI  - Intercellular salicylic acid accumulation during compatible and incompatible
      Arabidopsis-Pseudomonas syringae interactions.
AB  - The phytohormone salicylic acid (SA) plays an important role in several disease
      resistance responses. During the Age-Related Resistance (ARR) response that
      occurs in mature Arabidopsis responding to Pseudomonas syringae pv tomato (Pst),
      SA accumulates in the intercellular space where it may act as an antimicrobial
      agent. Recently we measured intracellular and intercellular SA levels in young,
      ARR-incompetent plants responding to virulent and avirulent strains of Pst to
      determine if intercellular SA accumulation is a component of additional defense
      responses to Pst. In young plants virulent Pst suppressed both intra- and
      intercellular SA accumulation in a coronatine-dependent manner. In contrast, high
      levels of intra- and intercellular SA accumulated in response to avirulent Pst.
      Our results support the idea that SA accumulation in the intercellular space is
      an important component of multiple defense responses. Future research will
      include understanding how mature plants counteract the effects of coronatine
      during the ARR response. 

PMID- 25763619
TI  - Gene silencing of CCD7 and CCD8 in Phelipanche aegyptiaca by tobacco rattle virus
      system retarded the parasite development on the host.
AB  - Strigolactones are phytohormones that stimulate seed germination of parasitic
      plants including Phelipanche aegyptiaca. Strigolactones are derived from
      carotenoids via a pathway involving the carotenoid cleavage dioxygenases CCD7 and
      CCD8. We report here identification of PaCCD7 and PaCCD8 orthologous genes from
      P. aegyptiaca. Expression analysis of PaCCD7 and PaCCD8 genes showed significant
      variation in their transcript levels in seeds and tubercles of P. aegyptiaca at
      different developmental stages. These two parasitic PaCCD7 and PaCCD8 genes were
      silenced in P. aegyptiaca using a trans-silencing approach in Nicotiana
      benthamiana. The transient knock-down of PaCCD7 and PaCCD8 inhibited tubercle
      development and the infestation process in host plants. Our results suggest an
      important role of the strigolactone associated genes (PaCCD7 and PaCCD8) in the
      parasite life cycle. 

PMID- 25763620
TI  - Cytokinins promote onset of endoreplication by controlling cell cycle machinery.
AB  - The endocycle is a modified cell cycle in which DNA replication is repeated
      without mitosis or cytokinesis. The resultant DNA polyploidization, termed
      endoreplication, is usually associated with an increase in cell volume, and it
      plays an important role in sustaining plant growth and development. The onset the
      endocycle is caused by a reduction of mitotic CDK activity through selective
      degradation of mitotic cyclins. In Arabidopsis, CCS52A1 is a substrate-specific
      activator of an E3 ubiquitin ligase that mediates proteasomal degradation of
      mitotic cyclins, thereby playing an essential role in transition from the mitotic
      cell cycle to the endocycle. We have recently reported that the cytokinin
      activated transcription factor ARABIDOPSIS RESPONSE REGULATOR 2 (ARR2) binds to
      and activates the CCS52A1 promoter, and promotes the onset of the endocycle in
      roots. This regulation is not associated with auxin signaling, demonstrating that
      cytokinins have a crucial function in programmed induction of endoreplication by
      directly controlling the cell cycle machinery. 

PMID- 25763621
TI  - Actin polymerization drives polar growth in Arabidopsis root hair cells.
AB  - In plants, the actin cytoskeleton is a prime regulator of cell polarity, growth,
      and cytoplasmic streaming. Tip growth, as observed in root hairs, caulonema, and
      pollen tubes, is governed by many factors, including calcium gradients,
      exocytosis and endocytosis, reactive oxygen species, and the cytoskeleton.
      Several studies indicate that the polymerization of G-actin into F-actin also
      contributes to tip growth. The structure and function of F-actin within the
      apical dome is variable, ranging from a dense meshwork to sparse single
      filaments. The presence of multiple F-actin structures in the elongating apices
      of tip-growing cells suggests that this cytoskeletal array is tightly regulated.
      We recently reported that sublethal concentrations of fluorescently labeled
      cytochalasin could be used to visualize the distribution of microfilament plus
      ends using fluorescence microscopy, and found that the tip region of the growing
      root hair cells of a legume plant exhibits a clear response to the nodulation
      factors secreted by Rhizobium. (1) In this current work, we expanded our analysis
      using confocal microscopy and demonstrated the existence of highly dynamic
      fluorescent foci along Arabidopsis root hair cells. Furthermore, we show that the
      strongest fluorescence signal accumulates in the tip dome of the growing root
      hair and seems to be in close proximity to the apical plasma membrane. Based on
      these findings, we propose that actin polymerization within the dome of growing
      root hair cells regulates polar growth. 

PMID- 25763622
TI  - NADH-dependent glutamate synthase participated in ammonium assimilation in
      Arabidopsis root.
AB  - Higher plants have 2 GOGAT species, Fd-GOGAT and NADH-GOGAT. While Fd-GOGAT
      mainly assimilates ammonium in leaves, which is derived from photorespiration,
      the function of NADH-GOGAT, which is highly expressed in roots, (1) needs to be
      elucidated. The aim of this study was to clarify the role of NADH-GOGAT in
      Arabidopsis roots. The supply of ammonium to the roots caused an accumulation of
      NADH-GOGAT, while Fd-GOGAT 1 and Fd-GOGAT 2 showed no response. A promoter-GUS
      fusion analysis and immunohistochemistry showed that NADH-GOGAT was located in
      non-green tissues like vascular bundles, shoot apical meristem, pollen, stigma,
      and roots. The localization of NADH-GOGAT and Fd-GOGAT was not overlapped. NADH
      GOGAT T-DNA insertion lines showed a reduction of glutamate and biomass under
      normal CO2 conditions. These data emphasizes the importance of NADH-GOGAT in the
      ammonium assimilation of Arabidopsis roots. 

PMID- 25763623
TI  - Plant secretomics: identification, isolation, and biological significance under
      environmental stress.
AB  - Plant secretomes are the proteins secreted by the plant cells and are involved in
      the maintenance of cell wall structure, relationship between host and pathogen,
      communication between different cells in the plant, etc. Amalgamation of
      methodologies like bioinformatics, biochemical, and proteomics are used to
      separate, classify, and outline secretomes by means of harmonizing in planta
      systems and in vitro suspension cultured cell system (SSCs). We summed up and
      explained the meaning of secretome, methods used for the identification and
      isolation of secreted proteins from extracellular space and methods for the
      assessment of purity of secretome proteins in this review. Two D PAGE method and
      HPLC based methods for the analysis together with different bioinformatics tools
      used for the prediction of secretome proteins are also discussed. Biological
      significance of secretome proteins under different environmental stresses, i.e.,
      salt stress, drought stress, oxidative stress, etc., defense responses and plant
      interactions with environment are also explained in detail. 

PMID- 25763624
TI  - Tissue-specific transcriptional profiling of iron-deficient and cadmium-stressed
      rice using laser capture microdissection.
AB  - Several metals are essential nutrients for plants. However, they become toxic at
      high levels and deleteriously affect crop yield and quality. We recently reported
      the spatial gene expression profiles of iron (Fe)-deficient and cadmium (Cd)
      stressed rice using laser microdissection and microarray analysis. The roots of
      Fe-deficient and Cd-stressed rice were separated into the vascular bundle (VB),
      cortex (Cor), and epidermis plus exodermis (EP). In addition, vascular bundles
      from new and old leaves at the lowest node, which are important for metal
      distribution, were analyzed separately (newDC and oldDC, respectively). Genes
      expressed in a tissue-specific manner in the VB, Cor, EP, newDC, and oldDC formed
      large clusters. The genes upregulated in all of the VB, Cor, and EP by Fe
      deficiency formed a substantial cluster that was smaller than the tissue-specific
      clusters. Significant numbers of genes expressed in newDC or oldDC were also
      expressed in VB in roots, suggesting that vascular bundles in the lowest nodes
      and roots have a partially common function. The expression patterns of
      transporter families involved in metal homeostasis were investigated, and members
      of each family were either expressed differentially in each tissue or showed
      different responses to Fe deficiency. One potassium transporter gene, OsHAK22,
      was upregulated by Fe deficiency in VB, Cor, and EP, suggesting that OsHAK22 is
      involved in potassium transport associated with mugineic acids secretion. 

PMID- 25763625
TI  - DEWAX-mediated transcriptional repression of cuticular wax biosynthesis in
      Arabidopsis thaliana.
AB  - The aerial parts of plants are covered with a cuticular wax layer, which is the
      first barrier between a plant and its environment. Although cuticular wax
      deposition increases more in the light than in the dark, little is known about
      the molecular mechanisms underlying the regulation of cuticular wax biosynthesis.
      Recently DEWAX (Decrease Wax Biosynthesis) encoding an AP2/ERF transcription
      factor was found to be preferentially expressed in the epidermis and induced by
      darkness. Wax analysis of the dewax knockout mutant, wild type, and DEWAX
      overexpression lines (OX) indicates that DEWAX is a negative regulator of
      cuticular wax biosynthesis. DEWAX represses the expression of wax biosynthetic
      genes CER1, LACS2, ACLA2, and ECR via direct interaction with their promoters.
      Cuticular wax biosynthesis is negatively regulated twice a day by the expression
      of DEWAX; throughout the night and another for stomata closing. Taken together,
      it is evident that DEWAX-mediated negative regulation of the wax biosynthetic
      genes plays role in determining the total wax loads produced in Arabidopsis
      during daily dark and light cycles. In addition, significantly higher levels of
      DEWAX transcripts in leaves than stems suggest that DEWAX-mediated
      transcriptional repression might be involved in the organ-specific regulation of
      total wax amounts on plant surfaces. 

PMID- 25763626
TI  - A simple assay to identify peroxisomal proteins involved in 12-oxo-phytodienoic
      acid metabolism.
AB  - Peroxisomes are vital eukaryotic organelles that house a variety of metabolic
      functions. To fully define the proteome of plant peroxisomes, we recently
      performed a proteomic analysis of peroxisomes from etiolated Arabidopsis
      seedlings, verified the peroxisomal localization of candidate proteins by in vivo
      targeting analysis of fluorescent proteins, and subjected the T-DNA mutants of
      the newly confirmed proteins to a series of phenotypic analysis. Our reverse
      genetics approach revealed the role of a cysteine protease - Response to Drought
      21A-like Cysteine Protease1 (RDL1) - in seed germination, indole-3-butyric acid
      (IBA) beta-oxidation and stress response. Here, we developed a quick assay aimed
      at identifying peroxisomal proteins involved in the metabolism of 12-oxo
      phytodienoic acid (OPDA), which is converted to jasmonic acid in the peroxisome
      through beta-oxidation. We performed a survey of the same mutants analyzed in our
      previous reverse genetics study with this new assay by measuring the response of
      mutants to OPDA's inhibitory effect on root elongation. Mutants of RDL1 and
      SERINE CARBOXYPEPTIDASE-LIKE20 (SCPL20) exhibited statistically significant
      hypersensitivity to OPDA, indicating the potential involvement of these proteins
      in OPDA metabolism. This convenient assay may be used in the future to rapidly
      screen for mutants defective in OPDA metabolism or signaling. 

PMID- 25763627
TI  - Plant hemoglobin participation in cell fate determination.
AB  - Plant hemoglobins (Hbs) have been identified as master regulators in determining
      the developmental fate of specific cells during maize embryogenesis. Whether an
      embryogenic cell lives or undergoes programmed cell death (PCD) is modulated by
      Hbs, through their tight interactions with nitric oxide (NO) and auxin. During
      maize embryogenesis, Hb-suppressing cells accumulate NO, are depleted of auxin,
      and are committed to die. We propose that Hbs control cell fate by regulating NO
      and auxin homeostasis, and that this type of mechanism may influence other
      hormonal responses modulating plant behavior during development and stress
      conditions. 

PMID- 25763628
TI  - Volatile interaction between undamaged plants affects tritrophic interactions
      through changed plant volatile emission.
AB  - Volatile interactions between unattacked plants can lead to changes in their
      volatile emissions. Exposure of potato plants to onion plant volatiles results in
      increased emission of 2 terpenoids, (E)-nerolidol and TMTT. We investigated
      whether this is detectable by the ladybird Coccinella septempunctata. The odor of
      onion-exposed potato was significantly more attractive to ladybirds than that of
      unexposed potato. Further, a synthetic blend mimicking the volatile profile of
      onion-exposed potato was more attractive than a blend mimicking that of unexposed
      potato. When presented individually, TMTT was attractive to ladybirds whereas (E)
      nerolidol was repellent. Volatile exchange between unattacked plants and
      consequent increased attractiveness for ladybirds may be a mechanism that
      contributes to the increased abundance of natural enemies in complex plant
      habitats. 

PMID- 25763629
TI  - Alternation of flavonoid accumulation under drought stress in Arabidopsis
      thaliana.
AB  - Plants have developed mechanisms to protect themselves against both biotic and
      abiotic environmental stress. Specialized/secondary metabolism is one of the
      stress response mechanisms. Recently, we reported that flavonoids, a class of
      specialized metabolites, including flavonols and anthocyanins with strong radical
      scavenging activity contributed to the mitigation of oxidative and drought stress
      in Arabidopsis thaliana (Arabidopsis). However, the behavior of flavonoids during
      drought stress is still not well-documented. Herein we investigated the time
      series alternation of flavonoids in the aerial part of Arabidopsis (wild type,
      Col-0) during drought stress by LC-QTOF-MS. The drastic alternation of 5
      flavonols and 5 anthocyanins was revealed together with changes in marker
      metabolites of drought stress, e.g., proline, raffinose, and galactinol. These
      findings indicate that flavonols and anthocyanins can mitigate drought stress. 

PMID- 25763630
TI  - Menage a trois: the complex relationships between mitogen-activated protein
      kinases, WRKY transcription factors, and VQ-motif-containing proteins.
AB  - Out of the 34 members of the VQ-motif-containing protein (VQP) family, 10 are
      phosphorylated by the mitogen-activated protein kinases (MAPKs), MPK3 and MPK6.
      Most of these MPK3/6-targeted VQPs (MVQs) interacted with specific sub-groups of
      WRKY transcription factors in a VQ-motif-dependent manner. In some cases, the
      MAPK appears to phosphorylate either the MVQ or the WRKY, while in other cases,
      both proteins have been reported to act as MAPK substrates. We propose a network
      of dynamic interactions between members from the MAPK, MVQ and WRKY families -
      either as binary or as tripartite interactions. The compositions of the WRKY-MVQ
      transcriptional protein complexes may change - for instance, through MPK3/6
      mediated modulation of protein stability - and therefore control defense gene
      transcription. 

PMID- 25763631
TI  - Rice acyl-CoA-binding proteins OsACBP4 and OsACBP5 are differentially localized
      in the endoplasmic reticulum of transgenic Arabidopsis.
AB  - Acyl-CoA-binding proteins (ACBPs) are known to bind and transport acyl-CoA esters
      and phospholipids intracellularly. In our recent paper in the New Phytologist, we
      reported that the six acyl-CoA-binding proteins (OsACBPs) in rice (Oryza sativa)
      are distributed across various subcellular compartments in transgenic Arabidopsis
      (Arabidopsis thaliana) such as the cytosol (OsACBP1, OsACBP2 and OsACBP3), the
      endoplasmic reticulum (ER) including the tubules (OsACBP4 and OsACBP5) and the
      cisternae (OsACBP4), and the peroxisomes (OsACBP6). Localization of OsACBP4::GFP
      to the peripheral ER cisternae and the central cisternal ER-like structures in
      transgenic Arabidopsis distinguished it from OsACBP5::GFP. We further report that
      besides the ER, OsACBP4::GFP and OsACBP5::GFP were also targeted to the membrane
      of ER bodies and ER-derived spherical structures, respectively, in transgenic
      Arabidopsis. These findings support our previous conclusion that OsACBP4 and
      OsACBP5 are not redundant proteins in the ER. 

PMID- 25763632
TI  - Time-sequential observation of spindle and phragmoplast orientation in BY-2 cells
      with altered cortical actin microfilament patterning.
AB  - Precise division plane determination is essential for plant development. At
      metaphase, a dense actin microfilament meshwork appears on both sides of the cell
      center, forming a characteristic cortical actin microfilament twin peak pattern
      in BY-2 cells. We previously reported a strong correlation between altered
      cortical actin microfilament patterning and an oblique mitotic spindle
      orientation, implying that these actin microfilament twin peaks play a role in
      the regulation of mitotic spindle orientation. In the present study, time
      sequential observation was used to reveal the progression from oblique
      phragmoplast to oblique cell plate orientation in cells with altered cortical
      actin microfilament patterning. In contrast to cells with normal actin
      microfilament twin peaks, oblique phragmoplast reorientation was rarely observed
      in cells with altered cortical actin microfilament patterning. These results
      support the important roles of cortical actin microfilament patterning in
      division plane orientation. 

PMID- 25763633
TI  - Arabidopsis CAP1-mediated ammonium sensing required reactive oxygen species in
      plant cell growth.
AB  - [Ca(2+)]cyt-associated protein kinase (CAP) gene 1 is a receptor-like kinase that
      belongs to CrRLK1L (Catharanthus roseus Receptor like kinase) subfamily. CAP1 has
      been identified as a novel modulator of NH4(+) in the tonoplast, which regulates
      root hair growth by maintaining the cytoplasmic Ca(2+) gradients. Different
      expression pattern of tonoplast intrinsic protein (TIP2;3) in the CAP1 knock out
      mutant and wild type on Murashige and Skoog (MS) medium suggested that CAP1
      influences transport activity to regulate the compartmentalization of NH4(+) into
      vacuole. Lower expression level of Oxidative Signal-Inducible1(OXI1) in the cap1
      1 root and the abnormal reactive oxygen species (ROS) gradient in root hair of
      cap1-1 on MS medium indicated that ROS signaling involve in CAP1-regulated root
      hair growth. Wild-type-like ROS distribution pattern in the cap1-1 root hair can
      be reestablished in seedlings grown on NH4(+) deficient medium, which indicated
      that CAP1 functions as a sensor for NH4(+) signaling in maintaining tip-focused
      ROS gradient in root hairs polar growth. 

PMID- 25763634
TI  - Reduced mu suppression and altered motor resonance in euthymic bipolar disorder:
      Evidence for a dysfunctional mirror system?
AB  - Social cognitive difficulties are common in the acute phase of bipolar disorder
      and, to a lesser extent, during the euthymic stage, and imaging studies of social
      cognition in euthymic bipolar disorder have implicated mirror system brain
      regions. This study aimed to use a novel multimodal approach (i.e., including
      both transcranial magnetic stimulation (TMS) and electroencephalogram (EEG)) to
      investigate mirror systems in bipolar disorder. Fifteen individuals with euthymic
      bipolar disorder and 16 healthy controls participated in this study. Single-pulse
      TMS was applied to the optimal site in the primary motor cortex (M1), which
      stimulates the muscle of interest during the observation of hand movements (goal
      directed or interacting) designed to elicit mirror system activity. Single EEG
      electrodes (C3, CZ, C4) recorded mu rhythm modulation concurrently. Results
      revealed that the patient group showed significantly less mu suppression compared
      to healthy controls. Surprisingly, motor resonance was not significantly
      different overall between groups; however, bipolar disorder participants showed a
      pattern of reduced reactivity on some conditions. Although preliminary, this
      study indicates a potential mirror system deficit in euthymic bipolar disorder,
      which may contribute to the pathophysiology of the disorder. 

PMID- 25763635
TI  - Calcitriol prevents in vitro vascular smooth muscle cell mineralization by
      regulating calcium-sensing receptor expression.
AB  - Vascular calcification (VC) is a degenerative disease that contributes to
      cardiovascular morbidity and mortality. A negative relationship has been
      demonstrated between VC and calcium sensing receptor (CaSR) expression in the
      vasculature. Of interest, vitamin D response elements, which allow responsiveness
      to 1,25-dihydroxyvitamin D3 [1,25(OH)2D3], are present in the promoters of the
      CaSR gene. We hypothesized that 1,25(OH)2D3, by modulating CaSR expression in
      vascular smooth muscle cells (VSMCs), might protect against VC. Human VSMCs were
      exposed to increasing concentrations of 1,25(OH)2D3 (0.01-10 nmol/L) in
      noncalcifying (1.8 mmol/L) or procalcifying Ca(2+)0 condition (5.0 mmol/L). Using
      quantitative RT-PCR and Western blotting we observed a significant increase in
      both CaSR mRNA and protein levels after exposure to 1.0 nmol/L 1,25(OH)2D3. This
      effect was associated with a maximal increase in CaSR expression at the cell
      surface after 48 hours of 1,25(OH)2D3 treatment, as assessed by flow cytometry.
      Down-regulation of the vitamin D receptor by small interfering RNA abolished
      these effects. In the procalcifying condition, 1.0 nmol/L 1,25(OH)2D3 blocked the
      Ca(2+)0-induced decrease in total and surface CaSR expression and protected
      against mineralization. Down-regulation of CaSR expression by CaSR small
      interfering RNA abolished this protective effect. 1,25(OH)2D3 concentrations of
      0.5 and 5.0 nmol/L were also effective, but other (0.01, 0.1, and 10 nmol/L)
      concentrations did not modify CaSR expression and human VSMC mineralization. In
      conclusion, these findings suggest that nanomolar concentrations of 1,25(OH)2D3
      induce a CaSR-dependent protection against VC. Both lower and higher
      concentrations are either ineffective or may even promote VC. Whether this also
      holds true in the clinical setting requires further study. 

PMID- 25763636
TI  - Fetal Exposure to Sertraline Hydrochloride Impairs Pancreatic beta-Cell
      Development.
AB  - Ten percent to 15% of women take selective serotonin reuptake inhibitor (SSRI)
      antidepressants during pregnancy. Offspring exposed to SSRIs are more likely to
      have low birth weight; this is associated with an increased risk of development
      of diabetes in adulthood in part due to altered pancreatic development. The
      effects of perinatal exposure to SSRIs on pancreatic development are unknown.
      Therefore, the objective of this study was to determine the effect of fetal
      exposure to sertraline hydrochloride on pregnancy outcomes and pancreatic
      development. Wistar rats were given vehicle (n = 5) or sertraline hydrochloride
      (10 mg/kg/d; n = 8) via daily subcutaneous injection from the confirmation of
      mating until parturition. Results from this animal model demonstrated that
      offspring born to sertraline-exposed dams have no changes in birth weight but had
      a reduction in pancreatic beta-cell area. The altered pancreatic islet
      development was a result of altered gene expression regulating islet development
      and survival. Therefore, fetal exposure to sertraline reduces beta-cell capacity
      at birth, raising concerns regarding the long-term metabolic sequelae of such
      exposures. 

PMID- 25763638
TI  - 17beta-estradiol inhibits MMP-9 and SUR1/TrpM4 expression and activation and
      thereby attenuates BSCB disruption/hemorrhage after spinal cord injury in male
      rats.
AB  - Blood-spinal cord barrier (BSCB) disruption and progressive hemorrhage after
      spinal cord injury (SCI) lead to secondary injury and the subsequent apoptosis
      and/or necrosis of neuron and glia, causing permanent neurological deficits. In
      this study, we examined the effect of 17beta-estradiol (E2) on BSCB breakdown and
      hemorrhage as well as subsequent inflammation after SCI. After a moderate
      contusion injury at the 9th thoracic segment of spinal cord, E2 (300 MUg/kg) was
      administered by iv injection immediately after SCI, and the same dose of E2 was
      then administered 6 and 24 hours after injury. Our data show that E2 attenuated
      BSCB permeability and hemorrhage and reduced the infiltration of neutrophils and
      macorphages after SCI. Consistent with this finding, the expression of
      inflammatory mediators was significantly reduced by E2. Furthermore, E2 treatment
      significantly inhibited the expression of sulfonylurea receptor 1 and transient
      receptor potential melastatin 4 after injury, which are known to mediate
      hemorrhage at an early stage after SCI. Moreover, the expression and activation
      of matrix metalloprotease-9 after injury, which is known to disrupt BSCB, and the
      degradation of tight junction proteins, such as zona occludens-1 and occludin,
      were significantly inhibited by E2 treatment. Furthermore, the protective effects
      of E2 on BSCB disruption and functional improvement were abolished by an estrogen
      receptor antagonist, ICI 182780 (3 mg/kg). Thus, our study provides evidence that
      the neuroprotective effect of E2 after SCI is, in part, mediated by inhibiting
      BSCB disruption and hemorrhage through the down-regulation of sulfonylurea
      receptor 1/transient receptor potential melastatin 4 and matrix metalloprotease
      9, which is dependent on estrogen receptor. 

PMID- 25763637
TI  - SIRT1 Relays Nutritional Inputs to the Circadian Clock Through the Sf1 Neurons of
      the Ventromedial Hypothalamus.
AB  - Circadian rhythms govern homeostasis and organism physiology. Nutritional cues
      act as time givers, contributing to the synchronization between central and
      peripheral clocks. Neuronal food-synchronized clocks are thought to reside in
      hypothalamic nuclei such as the ventromedial hypothalamus (VMH) and the
      dorsomedial hypothalamus or extrahypothalamic brain areas such as nucleus
      accumbens. Interestingly, the metabolic sensor of nicotinamide adenine
      dinucleotide-dependent deacetylase sirtuin-1 (SIRT1) is highly expressed in the
      VMH and was shown to contribute to both control of energy balance and clock
      function. We used mice with targeted ablation of Sirt1 in the steroidogenic
      factor 1 neurons of the VMH to gain insight on the role played by this
      deacetylase in the modulation of the central clock by nutritional inputs. By
      studying circadian behavior and circadian gene expression, we reveal that SIRT1
      operates as a metabolic sensor connecting food intake to circadian behavior.
      Indeed, under food restriction and absence of light, SIRT1 in the VMH contributes
      to activity behavior and circadian gene expression in the suprachiasmatic
      nucleus. Thus, under specific physiological conditions, SIRT1 contributes to the
      modulation of the circadian clock by nutrients. 

PMID- 25763639
TI  - Adipose VEGF Links the White-to-Brown Fat Switch With Environmental, Genetic, and
      Pharmacological Stimuli in Male Mice.
AB  - Living in an enriched environment (EE) decreases adiposity, increases energy
      expenditure, causes resistance to diet induced obesity, and induces brown-like
      (beige) cells in white fat via activating a hypothalamic-adipocyte axis. Here we
      report that EE stimulated vascular endothelial growth factor (VEGF) expression in
      a fat depot-specific manner prior to the emergence of beige cells. The VEGF up
      regulation was independent of hypoxia but required intact sympathetic tone to the
      adipose tissue. Targeted adipose overexpression of VEGF reproduced the browning
      effect of EE. Adipose-specific VEGF knockout or pharmacological VEGF blockade
      with antibodies abolished the induction of beige cell by EE. Hypothalamic brain
      derived neurotrophic factor stimulated by EE regulated the adipose VEGF
      expression, and VEGF signaling was essential to the hypothalamic brain-derived
      neurotrophic factor-induced white adipose tissue browning. Furthermore, VEGF
      signaling was essential to the beige cells induction by exercise, a beta3
      adrenergic agonist, and a peroxisome proliferator-activated receptor-gamma
      ligand, suggesting a common downstream pathway integrating diverse upstream
      mechanisms. Exploiting this pathway may offer potential therapeutic interventions
      to obesity and metabolic diseases. 

PMID- 25763640
TI  - Inhibition of Small Maf Function in Pancreatic beta-Cells Improves Glucose
      Tolerance Through the Enhancement of Insulin Gene Transcription and Insulin
      Secretion.
AB  - The large-Maf transcription factor v-maf musculoaponeurotic fibrosarcoma oncogene
      homolog A (MafA) has been found to be crucial for insulin transcription and
      synthesis and for pancreatic beta-cell function and maturation. However, insights
      about the effects of small Maf factors on beta-cells are limited. Our goal was to
      elucidate the function of small-Maf factors on beta-cells using an animal model
      of endogenous small-Maf dysfunction. Transgenic (Tg) mice with beta-cell-specific
      expression of dominant-negative MafK (DN-MafK) experiments, which can suppress
      the function of all endogenous small-Mafs, were fed a high-fat diet, and their in
      vivo phenotypes were evaluated. Phenotypic analysis, glucose tolerance tests,
      morphologic examination of beta-cells, and islet experiments were performed. DN
      MafK-expressed MIN6 cells were also used for in vitro analysis. The results
      showed that DN-MafK expression inhibited endogenous small-Maf binding to insulin
      promoter while increasing MafA binding. DN-MafK Tg mice under high-fat diet
      conditions showed improved glucose metabolism compared with control mice via
      incremental insulin secretion, without causing changes in insulin sensitivity or
      MafA expression. Moreover, up-regulation of insulin and glucokinase gene
      expression was observed both in vivo and in vitro under DN-MafK expression. We
      concluded that endogenous small-Maf factors negatively regulates beta-cell
      function by competing for MafA binding, and thus, the inhibition of small-Maf
      activity can improve beta-cell function. 

PMID- 25763642
TI  - Time-related grammatical use by children with SLI across languages: Beyond tense.
AB  - PURPOSE: For years, investigators have studied the use of tense by children with
      specific language impairment (SLI). This review article provides a summary of
      research on the use of other time-related grammatical forms by these children.
      METHOD: The literature on children's use of grammatical and lexical aspect, modal
      verbs and temporal adverbs is reviewed. Findings from children with SLI acquiring
      a range of different languages are considered. RESULT: Grammatical aspect and
      lexical aspect appear to be special weaknesses in children with SLI and problems
      with lexical aspect may also have an adverse effect on these children's ability
      to use past tense morphology. Although children with SLI are below age level in
      their use of modal verbs and temporal adverbs, the available evidence suggests
      that these weaknesses are no greater than these children's more general
      limitations with language. CONCLUSION: The evidence thus far indicates that time
      related notions further on the morphosyntactic end of the language continuum
      (aspect) are more problematic for these children than those time-related notions
      (modals, temporal adverbs) that include a pragmatic and/or semantic component. In
      some languages, aspect may prove to be a useful clinical marker of this disorder.

PMID- 25763643
TI  - Phyto-Extraction of Nickel by Linum usitatissimum in Association with Glomus
      intraradices.
AB  - Plants show enhanced phytoremediation of heavy metal contaminated soils
      particularly in response to fungal inoculation. Present study was conducted to
      find out the influence of Nickel (Ni) toxicity on plant biomass, growth,
      chlorophyll content, proline production and metal accumulation by L.
      usitatissimum (flax) in the presence of Glomus intraradices. Flax seedlings of
      both inoculated with G. intraradices and non-inoculated were exposed to different
      concentrations i.e., 250, 350 and 500 ppm of Ni at different time intervals.
      Analysis of physiological parameters revealed that Ni depressed the growth and
      photosynthetic activity of plants. However, the inoculation of plants with
      arbuscular mycorrhizae (G. intraradices) partially helped in the alleviation of
      Ni toxicity as indicated by improved plant growth under Ni stress. Ni uptake of
      non- mycorrhizal flax plants was increased by 98% as compared to control
      conditions whereas inoculated plants showed 19% more uptake when compared with
      the non-inoculated plants. Mycorrhizal plants exhibited increasing capacity to
      remediate contaminated soils along with improved growth. Thus, AM assisted
      phytoremediation helps in the accumulation of Ni in plants to reclaim Ni toxic
      soils. Based on our findings, it can be concluded that the role of flax plants
      and mycorrhizal fungi is extremely important in phytoremediation.

PMID- 25763641
TI  - Developmental programming: exposure to testosterone excess disrupts steroidal and
      metabolic environment in pregnant sheep.
AB  - Gestational exposure to excess T leads to intrauterine growth restriction, low
      birth weight, and adult metabolic/reproductive disorders in female sheep. We
      hypothesized that as early mediators of such disruptions, gestational T disrupts
      steroidal and metabolic homeostasis in both the mother and fetus by both
      androgenic and metabolic pathways. Maternal blood samples were measured weekly
      for levels of insulin, glucose, and progesterone from four groups of animals:
      control; gestational T (twice weekly im injections of 100 mg of T propionate from
      d 30 to d 90 of gestation); T plus an androgen antagonist, flutamide (15 mg/kg.d
      oral; T-Flutamide); and T plus the insulin sensitizer, rosiglitazone (0.11
      mg/kg.d oral; T-Rosi) (n = 10-12/group). On day 90 of gestation, maternal and
      umbilical cord samples were collected after a 48-hour fast from a subset (n =
      6/group) for the measurement of steroids, free fatty acids, amino acids, and
      acylcarnitines. Gestational T decreased maternal progesterone levels by 36.5% (P
      < .05), which was prevented by flutamide showing direct androgenic mediation.
      Gestational T also augmented maternal insulin levels and decreased medium chained
      acylcarnitines, suggesting increased mitochondrial fatty acid oxidation. These
      changes were prevented by rosiglitazone, suggesting alterations in maternal fuel
      use. Gestational T-induced increases in fetal estradiol were not prevented by
      either cotreatment. Gestational T disrupted associations of steroids with
      metabolites and progesterone with acylcarnitines, which was prevented either by
      androgen antagonist or insulin sensitizer cotreatment. These findings suggest a
      future combination of these treatments might be required to prevent alteration in
      maternal/fetal steroidal and metabolic milieu(s). 

PMID- 25763644
TI  - Ambient ionisation mass spectrometry for lipid profiling and structural analysis
      of mammalian oocytes, preimplantation embryos and stem cells.
AB  - Lipids play fundamental roles in mammalian embryo preimplantation development and
      cell fate. Triacylglycerol accumulates in oocytes and blastomeres as lipid
      droplets, phospholipids influence membrane functional properties, and essential
      fatty acid metabolism is important for maintaining the stemness of cells cultured
      in vitro. The growing impact that lipids have in the field of developmental
      biology makes analytical approaches to analyse structural information of great
      interest. This paper describes the concept and presents the results of lipid
      profiling by mass spectrometry (MS) of oocytes and preimplantation embryos, with
      special focus on ambient ionisation. Based on our previous experience with
      oocytes and embryos, we aim to convey that ambient MS is also valuable for stem
      cell differentiation analysis. Ambient ionisation MS allows the detection of a
      wide range of lipid classes (e.g. free fatty acids, cholesterol esters,
      phospholipids) in single oocytes, embryos and cell pellets, which are informative
      of in vitro culture impact, developmental and differentiation stages. Background
      on MS principles, the importance of underused MS scan modes for structural
      analysis of lipids, and statistical approaches used for data analysis are
      covered. We envisage that MS alone or in combination with other techniques will
      have a profound impact on the understanding of lipid metabolism, particularly in
      early embryo development and cell differentiation research. 

PMID- 25763645
TI  - Sensor-based auto-focusing system using multi-scale feature extraction and phase
      correlation matching.
AB  - This paper presents a novel auto-focusing system based on a CMOS sensor
      containing pixels with different phases. Robust extraction of features in a
      severely defocused image is the fundamental problem of a phase-difference auto
      focusing system. In order to solve this problem, a multi-resolution feature
      extraction algorithm is proposed. Given the extracted features, the proposed auto
      focusing system can provide the ideal focusing position using phase correlation
      matching. The proposed auto-focusing (AF) algorithm consists of four steps: (i)
      acquisition of left and right images using AF points in the region-of-interest;
      (ii) feature extraction in the left image under low illumination and out-of-focus
      blur; (iii) the generation of two feature images using the phase difference
      between the left and right images; and (iv) estimation of the phase shifting
      vector using phase correlation matching. Since the proposed system accurately
      estimates the phase difference in the out-of-focus blurred image under low
      illumination, it can provide faster, more robust auto focusing than existing
      systems. 

PMID- 25763646
TI  - DCPVP: distributed clustering protocol using voting and priority for wireless
      sensor networks.
AB  - This paper presents a new clustering protocol for designing energy-efficient
      hierarchical wireless sensor networks (WSNs) by dividing the distributed sensor
      network into virtual sensor groups to satisfy the scalability and prolong the
      network lifetime in large-scale applications. The proposed approach is a
      distributed clustering protocol called DCPVP, which is based on voting and
      priority ideas. In the DCPVP protocol, the size of clusters is based on the
      distance of nodes from the data link such as base station (BS) and the local node
      density. The cluster heads are elected based on the mean distance from neighbors,
      remaining energy and the times of being elected as cluster head. The performance
      of the DCPVP protocol is compared with some well-known clustering protocols in
      literature such as the LEACH, HEED, WCA, GCMRA and TCAC protocols. The simulation
      results confirm that the prioritizing- and voting-based election ideas decrease
      the construction time and the energy consumption of clustering progress in sensor
      networks and consequently improve the lifetime of networks with limited resources
      and battery powered nodes in harsh and inaccessible environments. 

PMID- 25763647
TI  - Tightly coupled integration of ionosphere-constrained precise point positioning
      and inertial navigation systems.
AB  - The continuity and reliability of precise GNSS positioning can be seriously
      limited by severe user observation environments. The Inertial Navigation System
      (INS) can overcome such drawbacks, but its performance is clearly restricted by
      INS sensor errors over time. Accordingly, the tightly coupled integration of GPS
      and INS can overcome the disadvantages of each individual system and together
      form a new navigation system with a higher accuracy, reliability and
      availability. Recently, ionosphere-constrained (IC) precise point positioning
      (PPP) utilizing raw GPS observations was proven able to improve both the
      convergence and positioning accuracy of the conventional PPP using ionosphere
      free combined observations (LC-PPP). In this paper, a new mode of tightly coupled
      integration, in which the IC-PPP instead of LC-PPP is employed, is implemented to
      further improve the performance of the coupled system. We present the detailed
      mathematical model and the related algorithm of the new integration of IC-PPP and
      INS. To evaluate the performance of the new tightly coupled integration, data of
      both airborne and vehicle experiments with a geodetic GPS receiver and tactical
      grade inertial measurement unit are processed and the results are analyzed. The
      statistics show that the new approach can further improve the positioning
      accuracy compared with both IC-PPP and the tightly coupled integration of the
      conventional PPP and INS. 

PMID- 25763648
TI  - Fracture of human femur tissue monitored by acoustic emission sensors.
AB  - The study describes the acoustic emission (AE) activity during human femur tissue
      fracture. The specimens were fractured in a bending-torsion loading pattern with
      concurrent monitoring by two AE sensors. The number of recorded signals
      correlates well with the applied load providing the onset of micro-fracture at
      approximately one sixth of the maximum load. Furthermore, waveform frequency
      content and rise time are related to the different modes of fracture (bending of
      femur neck or torsion of diaphysis). The importance of the study lies mainly in
      two disciplines. One is that, although femurs are typically subjects of surgical
      repair in humans, detailed monitoring of the fracture with AE will enrich the
      understanding of the process in ways that cannot be achieved using only the
      mechanical data. Additionally, from the point of view of monitoring techniques,
      applying sensors used for engineering materials and interpreting the obtained
      data pose additional difficulties due to the uniqueness of the bone structure. 

PMID- 25763649
TI  - Fortified anonymous communication protocol for location privacy in WSN: a modular
      approach.
AB  - Wireless sensor network (WSN) consists of many hosts called sensors. These
      sensors can sense a phenomenon (motion, temperature, humidity, average, max, min,
      etc.) and represent what they sense in a form of data. There are many
      applications for WSNs including object tracking and monitoring where in most of
      the cases these objects need protection. In these applications, data privacy
      itself might not be as important as the privacy of source location. In addition
      to the source location privacy, sink location privacy should also be provided.
      Providing an efficient end-to-end privacy solution would be a challenging task to
      achieve due to the open nature of the WSN. The key schemes needed for end-to-end
      location privacy are anonymity, observability, capture likelihood, and safety
      period. We extend this work to allow for countermeasures against multi-local and
      global adversaries. We present a network model protected against a sophisticated
      threat model: passive /active and local/multi-local/global attacks. This work
      provides a solution for end-to-end anonymity and location privacy as well. We
      will introduce a framework called fortified anonymous communication (FAC)
      protocol for WSN. 

PMID- 25763650
TI  - Accurate calibration and uncertainty estimation of the normal spring constant of
      various AFM cantilevers.
AB  - Measurement of force on a micro- or nano-Newton scale is important when exploring
      the mechanical properties of materials in the biophysics and nanomechanical
      fields. The atomic force microscope (AFM) is widely used in microforce
      measurement. The cantilever probe works as an AFM force sensor, and the spring
      constant of the cantilever is of great significance to the accuracy of the
      measurement results. This paper presents a normal spring constant calibration
      method with the combined use of an electromagnetic balance and a homemade AFM
      head. When the cantilever presses the balance, its deflection is detected through
      an optical lever integrated in the AFM head. Meanwhile, the corresponding bending
      force is recorded by the balance. Then the spring constant can be simply
      calculated using Hooke's law. During the calibration, a feedback loop is applied
      to control the deflection of the cantilever. Errors that may affect the stability
      of the cantilever could be compensated rapidly. Five types of commercial
      cantilevers with different shapes, stiffness, and operating modes were chosen to
      evaluate the performance of our system. Based on the uncertainty analysis, the
      expanded relative standard uncertainties of the normal spring constant of most
      measured cantilevers are believed to be better than 2%. 

PMID- 25763651
TI  - Study of the interaction of trastuzumab and SKOV3 epithelial cancer cells using a
      quartz crystal microbalance sensor.
AB  - Analytical methods founded upon whole cell-based assays are of importance in
      early stage drug development and in fundamental studies of biomolecular
      recognition. Here we have studied the binding of the monoclonal antibody
      trastuzumab to human epidermal growth factor receptor 2 (HER2) on human ovary
      adenocarcinoma epithelial cancer cells (SKOV3) using quartz crystal microbalance
      (QCM) technology. An optimized procedure for immobilizing the cells on the chip
      surface was established with respect to fixation procedure and seeding density.
      Trastuzumab binding to the cell decorated sensor surface was studied, revealing a
      mean dissociation constant, KD, value of 7 +/- 1 nM (standard error of the mean).
      This study provides a new perspective on the affinity of the antibody-receptor
      complex presented a more natural context compared to purified receptors. These
      results demonstrate the potential for using whole cell-based QCM assay in drug
      development, the screening of HER2 selective antibody-based drug candidates, and
      for the study of biomolecular recognition. This real time, label free approach
      for studying interactions with target receptors present in their natural
      environment afforded sensitive and detailed kinetic information about the binding
      of the analyte to the target. 

PMID- 25763652
TI  - An evaluation of skylight polarization patterns for navigation.
AB  - Skylight polarization provides a significant navigation cue for certain
      polarization-sensitive animals. However, the precision of the angle of
      polarization (AOP) of skylight for vehicle orientation is not clear. An
      evaluation of AOP must be performed before it is utilized. This paper reports an
      evaluation of AOP of skylight by measuring the skylight polarization patterns of
      clear and cloudy skies using a full-sky imaging polarimetry system. AOP
      measurements of skylight are compared with the pattern calculated by the single
      scattering Rayleigh model and these differences are quantified. The relationship
      between the degree of polarization (DOP) and the deviation of AOP of skylight is
      thoroughly studied. Based on these, a solar meridian extracted method is
      presented. The results of experiments reveal that the DOP is a key parameter to
      indicate the accuracy of AOP measurements, and all the output solar meridian
      orientations extracted by our method in both clear and cloudy skies can achieve a
      high accuracy for vehicle orientation. 

PMID- 25763653
TI  - Synthesis, Biological Evaluation, and Computer-Aided Drug Designing of New
      Derivatives of Hyperactive Suberoylanilide Hydroxamic Acid Histone Deacetylase
      Inhibitors.
AB  - The synthesis and biological evaluation of a novel series of compounds based on
      suberoylanilide hydroxamic acid (SAHA) had been designed as potential histone
      deacetylase inhibitors (HDACis). Molecular docking studies indicated that our
      derivatives had better fitting in the binding sites of HDAC8 than SAHA. Compounds
      1-5 were synthesized through the synthetic routes. In biological test, compounds
      also showed good inhibitory activity in HDAC enzyme assay and more potent growth
      inhibition in human glioma cell lines (MGR2, U251, and U373). A representative
      compound, N3F, exhibited better inhibitory effect (HDAC, IC50  = 0.1187 MUm;
      U251, IC50  = 0.8949 MUm) and lower toxicity for human normal cells (LO2, IC50  =
      172.5 MUm and MRC5, IC50  = 213.6 MUm) compared with SAHA (HDAC, IC50  = 0.8717
      MUm; U251, IC50  = 8.938 MUm; LO2, IC50  = 86.52 MUm and MRC5, IC50  = 81.02
      MUm). In addition, N3F obviously increased Beclin-1 and Caspase-3 and 9 as well
      as inhibited Bcl-2 in U251 cells. All of our results indicated that these SAHA
      cap derivatives could serve as potential lead compounds for further optimization.
      In addition, N3F and N2E both displayed promising profile as antitumor candidates
      for the treatment of human glioma. 

PMID- 25763654
TI  - Gallbladder agenesis with intrahepatic and extrahepatic bile duct stones and
      abnormal channel between right posterior lobe and duodenum.

PMID- 25763655
TI  - Buerger's disease mimicking cutaneous polyarteritis nodosa.

PMID- 25763656
TI  - Myeloid sarcoma: an unusual presentation for acute tracheal stenosis.
AB  - BACKGROUND AND AIMS: Extramedullary involvement of acute myelogenous leukemia
      (AML) is rare and has been reported under the terms myeloid sarcoma (MS),
      granulocytic sarcoma, chloroma, extramedullary acute myeloid leukemia,
      myeloblastoma and myelosarcoma. The most common extramedullary involvement
      includes soft tissues and lymph nodes, but it may arise in different sites of the
      body. There are only very few reports about MS in the pulmonary system, and
      involvement of the trachea is extremely rare. METHODS: This is the first report
      of initial presentation of MS by severe acute tracheal stenosis. RESULTS: After
      failed tracheal dilatation, a tracheostomy was performed where tracheal tissue
      was submitted for pathology. Histology of the tracheal biopsy and bone marrow
      revealed AML. The patient was subsequently referred to our oncology service for
      further management. CONCLUSION: Myeloid sarcoma should be part of the
      differential for acute tracheal stenosis.

PMID- 25763657
TI  - Effects of PAR and UV Radiation on the Structural and Functional Integrity of
      Phycocyanin, Phycoerythrin and Allophycocyanin Isolated from the Marine
      Cyanobacterium Lyngbya sp. A09DM.
AB  - An in vitro analysis of the effects of photosynthetically active and ultraviolet
      radiations was executed to assess the photostability of biologically relevant
      pigments phycocyanin (PC), phycoerythrin (PE) and allophycocyanin (APC) isolated
      from Lyngbya sp. A09DM. Ultraviolet (UV) irradiances significantly affected the
      integrity of PC, PE and APC; however, PAR showed least effect. UV radiation
      affected the bilin chromophores covalently attached to phycobiliproteins (PBPs).
      Almost complete elimination of the chromophore bands associated with alpha- and
      beta-subunit of PE and APC occurred after 4 h of UV-B exposure. After 5 h of UV-B
      exposure, the content of PC, PE and APC decreased by 51.65%, 96.8% and 96.53%,
      respectively. Contrary to PAR and UV-A radiation, a severe decrease in
      fluorescence of all PBPs was observed under UV-B irradiation. The fluorescence
      activity of extracted PBP was gradually inhibited immediately after 15-30 min of
      UV-B exposure. In comparison to the PC, the fluorescence properties of PE and APC
      were severely lost under UV-B radiation. Moreover, the present study indicates
      that UV-B radiation can damage the structural and functional integrity of
      phycobiliproteins leading to the loss of their ecological and biological
      functions. 

PMID- 25763658
TI  - Implementing evidence-based patient and family education on oral anticoagulation
      therapy: a community-based participatory project.
AB  - AIMS AND OBJECTIVES: This study aimed at developing and implementing evidence
      based patient and family education on oral anticoagulation therapy. BACKGROUND:
      The number of persons with chronic diseases who live at home is increasing. They
      have to manage multiple diseases and complex treatments. One such treatment is
      oral anticoagulation therapy, a high risk variable dose medication. Adherence to
      oral anticoagulation therapy is jeopardised by limited information about the
      medications, their risk and complications, the impact of individual daily routine
      and the limited inclusion of family members in education. Hence, improved and
      tailored education is essential for patients and families to manage oral
      anticoagulation therapy at home. DESIGN AND METHODS: A community-based
      participatory research design combined with the Precede-Proceed model was used
      including a systematic literature review, posteducation analysis, an online nurse
      survey, a documentation analysis and patient/family interviews. The study was
      conducted between April 2010-December 2012 at a department of general internal
      medicine in a teaching hospital in Switzerland. Participants were the
      department's nursing and medical professionals including the patients and their
      families. RESULTS: The evidence-based patient and family education on oral
      anticoagulation therapy emerged comprising a learning assessment, teaching units,
      clarification of responsibilities of nurse professionals and documentation
      guidelines. CONCLUSION AND CLINICAL RELEVANCE: The inclusion of the whole
      department has contributed to the development and implementation of this evidence
      based patient family education on oral anticoagulation therapy, which encompasses
      local characteristics and patient preferences. This education is now being used
      throughout the department.

PMID- 25763659
TI  - Data-driven directions for effective footwear provision for the high-risk
      diabetic foot.
AB  - AIMS: Custom-made footwear is used to offload the diabetic foot to prevent
      plantar foot ulcers. This prospective study evaluates the offloading effects of
      modifying custom-made footwear and aims to provide data-driven directions for the
      provision of effectively offloading footwear in clinical practice. METHODS:
      Eighty-five people with diabetic neuropathy and a recently healed plantar foot
      ulcer, who participated in a clinical trial on footwear effectiveness, had their
      custom-made footwear evaluated with in-shoe plantar pressure measurements at
      three-monthly intervals. Footwear was modified when peak pressure was >= 200 kPa.
      The effect of single and combined footwear modifications on in-shoe peak pressure
      at these high-pressure target locations was assessed. RESULTS: All footwear
      modifications significantly reduced peak pressure at the target locations
      compared with pre-modification levels (range -6.7% to -24.0%, P < 0.001). The
      metatarsal heads were most frequently targeted. Repositioning an existing (trans
      )metatarsal pad in the shoe insole (-15.9% peak pressure relief), applying local
      cushioning to the insole (-15.0%) and replacing the insole top cover with
      Plastazote (-14.2%) were the most effective single modifications. Combining a new
      Plastazote top cover with a trans-metatarsal bar (-24.0% peak pressure relief) or
      with local cushioning (-22.0%) were the most effective combined modifications.
      CONCLUSIONS: In people with diabetic neuropathy and a recently healed plantar
      foot ulcer, significant offloading can be achieved at high-risk foot regions by
      modifying custom-made footwear. These results provide data-driven directions for
      the design and evaluation of custom-made footwear for high-risk people with
      diabetes, and essentially mean that each shoe prescribed should incorporate those
      design features that effectively offload the foot.

PMID- 25763660
TI  - Melatonin regulates the rhythmic migration of neutrophils in live zebrafish.
AB  - The circadian clock plays a vital role in physiology and behavior such as the
      sleep-wake cycle and blood pressure and hormone levels. Immune responses also
      display circadian rhythmicity and particularly pineal melatonin contributes to
      immunological processes. Little attention, however, is given to mechanisms
      underlying rhythmic neutrophil responses to the injury. Here, we used a
      transgenic Tg(lyz:EGFP) zebrafish tail fin transection model to investigate
      whether the recruitment of neutrophils toward the injured site is regulated by
      the circadian clock. We found that migrating neutrophils display robust
      rhythmicity, peaking at darkness. Melatonin positively regulates rhythmic
      neutrophil migration, as evidenced that treatment with melatonin at low dosage
      can significantly enhance neutrophil recruitment toward the injured site, which
      is attenuated by luzindole treatment and in pinealectomized fish. Furthermore,
      using a transgenic zebrafish eyeball model, we observed that melatonin enhances
      secretion of two cytokines, TNF-alpha and IL-8, both of which markedly enhance
      neutrophil migration. Taken together, these results highlight a positive role of
      melatonin in rhythmic neutrophil migration and help obtain a better understanding
      of circadian regulation in immunology. 

PMID- 25763662
TI  - Physician assistants in Ghana.

PMID- 25763661
TI  - Fluoroquinolone resistance in bacteremic and low risk febrile neutropenic
      patients with cancer.
AB  - BACKGROUND: The low risk febrile neutropenic patients with Multinational
      Association for Supportive Care in Cancer (MASCC) score of more than 20 are
      recommended to be treated with fluoroquinolone-based oral treatment by the
      National Comprehensive Cancer Network (NCCN) guideline. This recommendation
      relies, at least partially, on the high sensitivity of the blood culture isolates
      to fluoroquinolone in clinical trials conducted in Western countries. Whether
      this also applies in middle or low income countries like China where antibiotic
      resistance is becoming prevalent recently has not been evaluated. METHODS: All
      the positive blood culture results from January 2010 to December 2013 in the 2
      large Chinese cancer centers were reviewed. The patients were included into the
      study with the following criteria: febrile neutropenia, solid tumor or lymphoma,
      MASCC score >20, positive blood cultures within two days of the onset of fever,
      and detailed treatment history. RESULTS: A total of 38 patients were included in
      this analysis. Two patients had polymicrobial bacteremia (Enterococcus faecalis
      and Flavimonas oryzihabitans). Other isolates included coagulase-negative
      staphylococcus, micrococcal species, viridans streptococci, Klebsiella
      pneumoniae, and Escherichia coli. The majority of the monomicrobial isolates from
      these 36 patients was Escherichia coli (28 patients, 74%). Notably, in contrast
      to the high sensitivity to fluoroquinolone from blood culture of the low risk
      patients in previous reports in Westen countries, a very high drug resistance was
      observed: 13 out of 28 Escherichia coli isolates (46%) or 14 out of all 38
      positive cultures (37%). CONCLUSION: The results warrant further validations in
      prospective clinical trials in countries where antibiotic resistance is prevalent
      to ensure appropriate antibiotic administration.

PMID- 25763663
TI  - Managing musculoskeletal infections in children in the era of increasing
      bacterial resistance.
AB  - The continually changing spectrum of bacterial resistance in children with
      musculoskeletal infections underscores the importance of prompt diagnosis coupled
      with timely and appropriate treatment. This article focuses on two serious
      childhood musculoskeletal infections commonly encountered by primary care
      providers: acute hematogenous osteomyelitis and septic arthritis. 

PMID- 25763664
TI  - Acquired lumbar spinal stenosis.
AB  - Lumbar spinal stenosis is the most frequent reason for spinal surgery in patients
      over age 65 years. In this condition, narrowing of the lumbar spinal canal and
      nerve root canals leads to painful, debilitating compression of spinal nerves and
      blood vessels. As the population ages, an increasing number of patients will be
      diagnosed and treated for lumbar spinal stenosis by primary care providers. This
      article reviews the pathophysiology, diagnosis, and management of lumbar spinal
      stenosis in adults over age 50 years. 

PMID- 25763665
TI  - The Minimum Data Set 3.0 Cognitive Function Scale.
AB  - BACKGROUND: The Minimum Data Set (MDS) 3.0 introduced the Brief Interview for
      Mental Status (BIMS), a short performance-based cognitive screener for nursing
      home (NH) residents. Not all residents are able to complete the BIMS and are
      consequently assessed by staff. We designed a Cognitive Function Scale (CFS)
      integrating self-report and staff-report data and present evidence of the scale's
      construct validity. DESIGN: A retrospective cohort study. SUBJECTS: The subjects
      consisted of 3 cohorts: (1) long-stay NH residents (N=941,077) and (2) new
      admissions (N=2,066,580) during 2011-2012, and (3) residents with the older MDS
      2.0 assessment in 2010 and the newer MDS 3.0 assessment (n=688,511). MEASURES:
      MDS 3.0 items were used to create a single, integrated 4-category hierarchical
      CFS that was compared with residents' prior MDS 2.0 Cognitive Performance Scale
      scores and other concurrent MDS 3.0 measures of construct validity. RESULTS: The
      new CFS suggests that 28% of the long-stay cohort in 2011-2012 were cognitively
      intact, 22% were mildly impaired, 33% were moderately impaired, and 17% were
      severely impaired. For the admission cohort, the CFS noted 56% as cognitively
      intact, 23% as mildly impaired, 17% as moderately impaired, and 4% as severely
      impaired. The CFS corresponded closely with residents' prior MDS 2.0 Cognitive
      Performance Scale scores and with performance of Activities of Daily Living, and
      nurses' judgments of function and behavior in both the admission and long-stay
      cohorts. CONCLUSIONS: The new CFS is valuable to researchers as it provides a
      single, integrated measure of NH residents' cognitive function, regardless of the
      mode of assessment.

PMID- 25763666
TI  - Malignant syphilis in a HIV infected patient.
AB  - We present a 47 year old female white HIV-1 infected patient with multiple
      painless rupioid skin lesions, a CD4 count of 155 cells/mm3, positive syphilis
      serology and a histopathology conspicuous for malignant syphilis. She could be
      successfully treated with Benzathine-Benzylpenicillin (Retarpen(r)) 2,4 Mega
      I.E., 3x intramuscularly in weekly intervals. 

PMID- 25763667
TI  - Sexually transmitted diseases, infections, and disorders: what's in a name?

PMID- 25763668
TI  - From the editor--tell us what you think: sexually transmitted disease, sexually
      transmitted infection, both, or neither.

PMID- 25763669
TI  - Bacterial sexually transmitted infections among HIV-infected patients in the
      United States: estimates from the Medical Monitoring Project.
AB  - BACKGROUND: Bacterial sexually transmitted infections may facilitate HIV
      transmission. Bacterial sexually transmitted infection testing is recommended for
      sexually active HIV-infected patients annually and more frequently for those at
      elevated sexual risk. We estimated percentages of HIV-infected patients in the
      United States receiving at least one syphilis, gonorrhea, or chlamydia test, and
      repeat (>=2 tests, >=3 months apart) tests for any of these sexually transmitted
      infections from mid-2008 through mid-2010. DESIGN: The Medical Monitoring Project
      collects behavioral and clinical characteristics of HIV-infected adults receiving
      medical care in the United States using nationally representative sampling.
      METHODS: Sexual activity included self-reported oral, vaginal, or anal sex in the
      past 12 months. Participants reporting more than 1 sexual partner or illicit drug
      use before/during sex in the past year were classified as having elevated sexual
      risk. Among participants with only 1 sex partner and no drug use before/during
      sex, those reporting consistent condom use were classified as low risk; those
      reporting sex without a condom (or for whom this was unknown) were classified as
      at elevated sexual risk only if they considered their sex partner to be a casual
      partner, or if their partner was HIV-negative or partner HIV status was unknown.
      Bacterial sexually transmitted infection testing was ascertained through medical
      record abstraction. RESULTS: Among sexually active patients, 55% were tested at
      least once in 12 months for syphilis, whereas 23% and 24% received at least one
      gonorrhea and chlamydia test, respectively. Syphilis testing did not vary by
      sex/sexual orientation. Receipt of at least 3 CD4+ T-lymphocyte cell counts
      and/or HIV viral load tests in 12 months was associated with syphilis testing in
      men who have sex with men (MSM), men who have sex with women only, and women.
      Chlamydia testing was significantly higher in sexually active women (30%)
      compared with men who have sex with women only (19%), but not compared with MSM
      (22%). Forty-six percent of MSM were at elevated sexual risk; 26% of these MSM
      received repeat syphilis testing, whereas repeat testing for gonorrhea and
      chlamydia was only 7% for each infection. CONCLUSIONS: Bacterial sexually
      transmitted infection testing among sexually active HIV-infected patients was
      low, particularly for those at elevated sexual risk. Patient encounters in which
      CD4+ T-lymphocyte cell counts and/or HIV viral load testing occurs present
      opportunities for increased bacterial sexually transmitted infection testing.

PMID- 25763670
TI  - Concurrent sexual partnerships among young heterosexual adults at increased HIV
      risk: types and characteristics.
AB  - BACKGROUND: The impact of concurrency on sexually transmitted infection
      transmission depends on coital frequency, condom use, duration of relationship
      overlap, and number of partners. Previous research has identified distinct
      concurrency types; however, little is known about their risk characteristics.
      METHODS: Men (n = 261) and women (n = 275) aged 18 to 30 years at increased risk
      for acquiring HIV were recruited from community locations in Los Angeles.
      Participants completed 4 in-person interviews for 12 months. Partnership data
      were used to characterize the prevalence of 4 types of concurrency: transitional
      (2 overlapping relationships in which the first relationship ended before the
      second), single day (a second relationship of 1 day's duration during the course
      of another relationship), contained (a second relationship >1 day began and ended
      during the course of another), and multiple (>=3 overlapping relationships).
      Multilevel random intercept models were used to estimate mean coital frequency,
      proportion of condom-protected acts, total duration of overlap, and lifetime sex
      partners. RESULTS: At baseline, 47% of male and 32% of female participants
      reported any type of concurrency in the previous 4 months, and 26% of men and 10%
      of women reported multiple concurrencies. Condom use ranged from 56% to 64%, with
      the highest use in transitional concurrency (61% for men, 68% for women) and the
      lowest in contained (52% for men, 54% for women). Coital frequency, total
      overlap, and lifetime sex partners also varied by concurrency type. CONCLUSIONS:
      Inconsistent condom use and repeated opportunities for exposure characterize
      common types of concurrency among high-risk young adults.

PMID- 25763671
TI  - Identifying psychosocial and social correlates of sexually transmitted diseases
      among black female teenagers.
AB  - BACKGROUND: Black teenagers have relatively high rates of sexually transmitted
      diseases (STDs), and recent research suggests the role of contextual factors, as
      well as risk behaviors. We explore the role of 4 categories of risk and
      protective factors on having a biologically confirmed STD among black, female
      teenagers. METHODS: Black teenage girls (14-19 years old) accessing services at a
      publicly funded family planning clinic provided a urine specimen for STD testing
      and completed an audio computer-assisted self-interview that assessed the
      following: risk behaviors, relationship characteristics, social factors, and
      psychosocial factors. We examined bivariate associations between each risk and
      protective factor and having gonorrhea and/or chlamydia, as well as multivariate
      logistic regression among 339 black female teenagers. RESULTS: More than one
      fourth (26.5%) of participants had either gonorrhea and/or chlamydia. In
      multivariate analyses, having initiated sex before age 15 (adjusted odds ratio
      [aOR], 1.87) and having concurrent sex partners in the past 6 months (aOR, 1.55)
      were positively associated with having an STD. Living with her father (aOR,
      0.44), believing that an STD is the worst thing that could happen (aOR, 0.50),
      and believing she would feel dirty and embarrassed about an STD (aOR, 0.44) were
      negatively associated with having an STD. CONCLUSIONS: Social factors and
      attitudes toward STDs and select risk behaviors were associated with the risk for
      STDs, suggesting the need for interventions that address more distal factors.
      Future studies should investigate how such factors influence safer sexual
      behaviors and the risk for STDs among black female teenagers.

PMID- 25763672
TI  - Sociodemographic and behavioral correlates of anogenital warts and human
      papillomavirus-related knowledge among men who have sex with men and transwomen
      in Lima, Peru.
AB  - BACKGROUND: Human papilloma virus (HPV) is the most common sexually transmitted
      infection (STI) globally, with a high burden of anogenital warts (AGW) among men
      who have sex with men (MSM) and transwomen (TW). METHODS: Six-hundred HIV
      negative MSM and TW (300 with AGW, 300 without) were recruited for a prospective
      cohort study to examine HPV outcomes and HPV vaccine knowledge. Participants
      completed a self-administered online questionnaire. Logistic regression was used
      to assess the association between sociodemographic and behavioral characteristics
      with HPV vaccine knowledge. RESULTS: The average participant age was 25.5 years.
      Most (67%) were single and 41.2% self-reported STI symptoms. The average age of
      first anal intercourse was 17 years, with self-reported sexual role as active
      (36%), passive (36%), and both (27%). Three quarters (77%) of participants
      reported engaging in condomless anal or oral sex up to six months prior to the
      study. Less than half (48%) of participants had heard of HPV. Participants with
      AGW were more likely to report that condoms helped prevent HPV (p=0.01) and that
      the absence of genital warts does not mean the absence of HPV (p < 0.01).
      CONCLUSION: Study participants had low levels of HPV knowledge but likely high
      HPV exposure due to condomless anal sex. The HPV knowledge gap may be explained
      in part by the stigma of sex work, underreporting of STIs, the high cost of the
      HPV vaccine in Peru, and misinformation about HPV vaccine. More work is needed to
      educate MSM and TW on HPV and the HPV vaccine.

PMID- 25763673
TI  - Factors associated with visible anogenital warts among HIV-uninfected Peruvian
      men who have sex with men and transwomen: a cross-sectional study.
AB  - BACKGROUND: Visible, anogenital warts may be associated with risk factors for HIV
      infection. This cross-sectional study examined the factors associated with
      visible anogenital warts among HIV-uninfected Peruvian men who have sex with men
      (MSM) and transwomen. METHODS: Six hundred HIV-uninfected MSM and transwomen were
      recruited from a community-based setting in metropolitan Lima, Peru, through
      outreach activities. Participants were tested for syphilis, completed a
      behavioral questionnaire, and were examined for visible anogenital warts.
      Logistic regression was used to assess the independent association between sample
      characteristics, HIV-related risk factors, and visible anogenital warts. RESULTS:
      A tertiary education versus a primary/secondary (adjusted odds ratio [AOR], 1.79;
      95% confidence interval [CI], 1.07-2.99), a first experience of anal intercourse
      at age 20 years or older versus younger ages (AOR, 2.80; 95% CI, 1.45-5.38), and
      self-reporting of current sexually transmitted infection symptoms (AOR, 2.38; 95%
      CI, 1.61-3.52) were significant correlates of visible anogenital warts, whereas
      syphilis infection, transactional sex, receptive anal intercourse, and self
      identifying as a transwoman were not. CONCLUSIONS: Although not associated with
      key risk factors for HIV infection in Peruvian MSM and transwomen, the presence
      of visible anogenital warts should prompt clinicians to consider the possibility
      of unreported same-sex sexual behaviors and other risk sexually transmitted
      infection/HIV risk factors.

PMID- 25763675
TI  - Trends of resistance to antimicrobials recommended currently and in the past for
      management of gonorrhea in the Apex STD center in India and comparison of
      antimicrobial resistance profile between 2002-2006 and 2007-2012.
AB  - BACKGROUND: Antimicrobial resistance in Neisseria gonorrhoeae jeopardizes public
      health and continues to spread out to currently recommended and older
      antimicrobial agents. Antimicrobial resistance (AMR) surveillance provides
      essential clues toward the modification of treatment guidelines. The aim of the
      study was to determine gonococcal AMR profile and trends between 2007 and 2012
      and to evaluate any change in AMR profile in comparison with published trends in
      2002 to 2006. METHODS: Antimicrobial susceptibility testing of 261 N. gonorrhoeae
      isolates from consecutive patients between 2007 and 2012 was determined for
      penicillin, tetracycline, ciprofloxacin, spectinomycin, extended-spectrum
      cephalosporins (ceftriaxone, cefixime, cefpodoxime) and azithromycin by the disk
      diffusion technique and the Etest method. P value was determined using chi test
      for comparisons of trends between the 2 periods. RESULTS: In comparison of AMR
      trends between 2002-2006 and 2007-2012, penicillinase-producing N. gonorrhoeae,
      tetracycline-resistant N. gonorrhoeae, and ciprofloxacin-resistant strains
      increased significantly from 21.2% to 47.9% (P < 0.0001), 13.6% to 25.3% (P =
      0.0002), and 78% to 89.7% (P = 0.0001), respectively. An insignificant increase
      from 2.4% to 4.2% (P > 0.05) in decreased susceptibility to ceftriaxone and 0.8%
      to 1.5% (P > 0.05) for azithromycin resistance was observed. All isolates were
      susceptible to spectinomycin over both the periods, except for one isolate in
      2002. CONCLUSIONS: The study highlights that there is a continuous increase in
      resistance to previously recommended antibiotics despite their disuse for
      treatment. The increase in number of strains with decreased susceptibility to
      extended-spectrum cephalosporins and azithromycin resistance, currently
      recommended for management of gonorrhea, is of serious concern. These trends
      should be monitored continuously to change antibiotic policy.

PMID- 25763674
TI  - Molecular genotyping of human papillomavirus l1 gene in low-risk and high-risk
      populations in Bangkok.
AB  - BACKGROUND: Human papillomavirus (HPV) infections in Thailand are a public health
      concern, but information on HPV infection in sex workers and men who have sex
      with men (MSM) is limited. The aim of this study was to measure the prevalence
      and genotype distribution of HPV among low- and high-risk, HIV-negative
      populations. METHODS: A total of 300 participants were categorized as general
      women, female sex workers, MSM, and MSM sex workers. Human papillomavirus
      infections were identified by the Papanicolaou test and nested polymerase chain
      reaction. A phylogenetic analysis of partial HPV L1 genes was performed. RESULTS:
      Abnormal cytology was found in 5% of general women, 10% of female sex workers,
      24% of MSM, and 28% of MSM sex workers. Human papillomavirus was detected in 9%
      of general women, 13% of female sex workers, and 30% in both MSM and the MSM sex
      workers. The prevalence of HPV high-risk genotypes was significantly higher in
      female sex workers and MSM, whereas low-risk genotypes and genital warts were
      significantly higher in MSM sex workers. Significantly more patients with genital
      warts and cervical intraepithelial neoplasia I/anal intraepithelial neoplasia I
      harbored low-risk genotypes, whereas those with cervical intraepithelial
      neoplasia II/anal intraepithelial neoplasia II harbored high-risk genotypes.
      CONCLUSIONS: High- and low-risk HPV genotypes persist in high-risk groups in
      Bangkok. Some genotypes infecting at-risk populations are not vaccine
      preventable. These findings may help to elucidate the prevalence of HPV
      infections in Thailand and serve as the basis for additional investigations into
      risk factors for these populations.

PMID- 25763676
TI  - Low viral suppression and high HIV diagnosis rate among men who have sex with men
      with syphilis--Baltimore, Maryland.
AB  - BACKGROUND: The burden of syphilis and HIV among gay, bisexual, and other men who
      have sex with men (MSM) in Baltimore, Maryland, is substantial. Syphilis and HIV
      surveillance data were analyzed to characterize MSM with syphilis, including
      those with repeat infection and HIV coinfection, to strengthen prevention
      efforts. METHODS: MSM 15 years or older from Baltimore City or County diagnosed
      as having early syphilis in 2010 to 2011 were included. Those previously treated
      for syphilis in 2007 to 2011 were considered to have repeat syphilis infection.
      HIV surveillance data were used to identify HIV coinfection and assess viral
      suppression. For MSM not diagnosed as having HIV at or before their syphilis
      diagnosis, annual HIV diagnosis rates were estimated, using Baltimore City data.
      RESULTS: Of 460 MSM with early syphilis in 2010 or 2011, 92 (20%) had repeat
      infection; 55% of MSM with a single diagnosis and 86% with repeat infection were
      HIV coinfected. Among MSM diagnosed as having HIV, viral suppression was low
      (25%, or 46% of those with a viral load reported). Among Baltimore City MSM
      without a prior HIV diagnosis, estimated annual HIV diagnosis rates were high (5%
      for those with 1 syphilis diagnosis, 23% for those with repeat infection).
      CONCLUSIONS: Baltimore-area MSM with syphilis, particularly those with repeat
      infection, represent a unique population for whom coinfection with HIV is high.
      Increasing frequency of syphilis and HIV testing among Baltimore area MSM with a
      syphilis diagnosis and prioritizing HIV-infected MSM with syphilis in efforts to
      achieve viral suppression may improve outcomes locally for both infections.

PMID- 25763677
TI  - Administration of hydrogen-rich saline in mice with allogeneic hematopoietic stem
      cell transplantation.
AB  - BACKGROUND: Hydrogen, as a novel antioxidant, has been shown to selectively
      reduce the level of hydroxyl radicals and alleviate acute oxidative stress in
      many animal experiments. Hydrogen-rich saline provides a high concentration of
      hydrogen that can be easily and safely applied. Allogeneic hematopoietic stem
      cell transplantation (HSCT) has been the most curative therapy for hematological
      malignancies. However, acute graft-versus-host disease (aGVHD) is the main cause
      of death in post-transplantation patients. In this study, we examined whether
      hydrogen-rich saline would show favorable effects on acute GVHD in mice. MATERIAL
      AND METHODS: After lethal irradiation, BALB/c mice received bone marrow
      transplantation from C57BL/6 mice. Hydrogen-rich saline (5 ml/kg) was given to
      recipient mice in the hydrogen group once a day by intraperitoneal injection, and
      saline (5 ml/kg) was given to recipient mice in the saline group. Survival rates
      were monitored, clinical and pathological scores of aGVHD were determined after
      bone marrow transplantation (BMT), and the serum cytokine levels were examined on
      the 7th day after BMT. RESULTS: This study proves that hydrogen-rich saline
      increased the survival rate, reduced clinical and histopathological scores of
      aGVHD, promoted the recovery of white blood cells, reduced the serum cytokine
      levels, and reversed tissue damage after transplantation in mice. CONCLUSIONS:
      Hydrogen has potential as an effective and safe therapeutic agent in aGVHD.

PMID- 25763679
TI  - Catalytic and highly enantioselective selenolactonization.
AB  - An enantioselective selenolactonization of olefinic acids has been developed
      using (DHQD)2PHAL as the catalyst. Structurally simple and commercially available
      N-phenylselenophthalimide was used as the electrophilic selenium reagent. The
      corresponding selenolactones could be obtained with up to 96% ee. 

PMID- 25763678
TI  - A taxonomy of voice therapy.
AB  - PURPOSE: Voice therapy practice and research, as in most types of rehabilitation,
      is currently limited by the lack of a taxonomy describing what occurs during a
      therapy session (with enough precision) to determine which techniques/components
      contribute most to treatment outcomes. To address this limitation, a
      classification system of voice therapy is proposed that integrates descriptions
      of therapeutic approaches from the clinical literature into a framework that
      includes relevant theoretical constructs. METHOD: Literature searches identified
      existing rehabilitation taxonomies/therapy classification schemes to frame an
      initial taxonomic structure. An additional literature search and review of
      clinical documentation provided a comprehensive list of therapy tasks. The
      taxonomy's structure underwent several iterations to maximize accuracy, intuitive
      function, and theoretical underpinnings while minimizing redundancy. The taxonomy
      was then used to classify established voice therapy programs. RESULTS: The
      taxonomy divided voice therapy into direct and indirect interventions delivered
      using extrinsic and/or intrinsic methods, and Venn diagrams depicted their
      overlapping nature. A dictionary was developed of the taxonomy's terms, and 7
      established voice therapy programs were successfully classified. CONCLUSION: The
      proposed taxonomy represents an important initial step toward a standardized
      voice therapy classification system expected to facilitate outcomes research and
      communication among clinical stakeholders.

PMID- 25763680
TI  - Improvement of cognitive function after cochlear implantation in elderly
      patients.
AB  - IMPORTANCE: The association between hearing impairment and cognitive decline has
      been established; however, the effect of cochlear implantation on cognition in
      profoundly deaf elderly patients is not known. OBJECTIVE: To analyze the
      relationship between cognitive function and hearing restoration with a cochlear
      implant in elderly patients. DESIGN, SETTING, AND PARTICIPANTS: Prospective
      longitudinal study performed in 10 tertiary referral centers between September 1,
      2006, and June 30, 2009. The participants included 94 patients aged 65 to 85
      years with profound, postlingual hearing loss who were evaluated before, 6 months
      after, and 12 months after cochlear implantation. INTERVENTIONS: Cochlear
      implantation and aural rehabilitation program. MAIN OUTCOMES AND MEASURES: Speech
      perception was measured using disyllabic word recognition tests in quiet and in
      noise settings. Cognitive function was assessed using a battery of 6 tests
      evaluating attention, memory, orientation, executive function, mental
      flexibility, and fluency (Mini-Mental State Examination, 5-word test, clock
      drawing test, verbal fluency test, d2 test of attention, and Trail Making test
      parts A and B). Quality of life and depression were evaluated using the Nijmegen
      Cochlear Implant Questionnaire and the Geriatric Depression Scale-4. RESULTS:
      Cochlear implantation led to improvements in speech perception in quiet and in
      noise (at 6 months: in quiet, 42% score increase [95% CI, 35%-49%; P < .001]; in
      noise, at signal to noise ratio [SNR] +15 dB, 44% [95% CI, 36%-52%, P < .001], at
      SNR +10 dB, 37% [95% CI 30%-44%; P < .001], and at SNR +5 dB, 27% [95% CI, 20%
      33%; P < .001]), quality of life, and Geriatric Depression Scale-4 scores (76% of
      patients gave responses indicating no depression at 12 months after implantation
      vs 59% before implantation; P = .02). Before cochlear implantation, 44% of the
      patients (40 of 91) had abnormal scores on 2 or 3 of 6 cognition tests. One year
      after implant, 81% of the subgroup (30 of 37) showed improved global cognitive
      function (no or 1 abnormal test score). Improved mean scores in all cognitive
      domains were observed as early as 6 months after cochlear implantation. Cognitive
      performance remained stable in the remaining 19% of the participants (7 of 37).
      Among patients with the best cognitive performance before implantation (ie, no or
      1 abnormal cognitive test score), 24% (12 of 50) displayed a slight decline in
      cognitive performance. Multivariate analysis to examine the association between
      cognitive abilities before implantation and the variability in cochlear implant
      outcomes demonstrated a significant effect only between long-term memory and
      speech perception in noise at 12 months (SNR +15 dB, P = .01; SNR +10 dB, P <
      .001; and SNR +5 dB, P = .02). CONCLUSIONS AND RELEVANCE: Rehabilitation of
      hearing communication through cochlear implantation in elderly patients results
      in improvements in speech perception and cognitive abilities and positively
      influences their social activity and quality of life. Further research is needed
      to assess the long-term effect of cochlear implantation on cognitive decline.

PMID- 25763681
TI  - Uncovering the formation and selection of benzylmalonyl-CoA from the biosynthesis
      of splenocin and enterocin reveals a versatile way to introduce amino acids into
      polyketide carbon scaffolds.
AB  - Selective modification of carbon scaffolds via biosynthetic engineering is
      important for polyketide structural diversification. Yet, this scope is currently
      restricted to simple aliphatic groups due to (1) limited variety of CoA-linked
      extender units, which lack aromatic structures and chemical reactivity, and (2)
      narrow acyltransferase (AT) specificity, which is limited to aliphatic CoA-linked
      extender units. In this report, we uncovered and characterized the first aromatic
      CoA-linked extender unit benzylmalonyl-CoA from the biosynthetic pathways of
      splenocin and enterocin in Streptomyces sp. CNQ431. Its synthesis employs a
      deamination/reductive carboxylation strategy to convert phenylalanine into
      benzylmalonyl-CoA, providing a link between amino acid and CoA-linked extender
      unit synthesis. By characterization of its selection, we further validated that
      AT domains of splenocin, and antimycin polyketide synthases are able to select
      this extender unit to introduce the phenyl group into their dilactone scaffolds.
      The biosynthetic machinery involved in the formation of this extender unit is
      highly versatile and can be potentially tailored for tyrosine, histidine and
      aspartic acid. The disclosed aromatic extender unit, amino acid-oriented
      synthetic pathway, and aromatic-selective AT domains provides a systematic
      breakthrough toward current knowledge of polyketide extender unit formation and
      selection, and also opens a route for further engineering of polyketide carbon
      scaffolds using amino acids. 

PMID- 25763682
TI  - Modular C-H functionalization cascade of aryl iodides.
AB  - We report the first example of ipso-borylation for the modular 1,2
      bisfunctionalization of aryl iodides via C-H functionalization. The carbon-boron
      bond is used as a lynchpin to access ipso carbon-carbon, carbon-nitrogen, carbon
      oxygen, and carbon-halogen (Cl, Br, I) bonds. The utility of our methodology is
      illustrated through quick, modular syntheses of the pharmaceuticals Abilify and
      Flunixin. 

PMID- 25763683
TI  - Palladium-catalyzed Cs2CO3-promoted arylation of unactivated C(sp(3))-H bonds by
      (diacetoxyiodo)arenes: shifting the reactivity of (diacetoxyiodo)arenes from
      acetoxylation to arylation.
AB  - PdCl2(CH3CN)2-catalyzed arylation of unactivated C(sp(3))-H bonds using
      (diacetoxyiodo)arenes as arylation reagents is reported. The reactivity of
      (diacetoxyiodo)arenes as arylation reagents is enabled in the presence of Cs2CO3
      under the reaction conditions. This arylation method is highly efficient and
      occurs without the use of silver salt. The reaction tolerates a broad substrate
      scope that was not demonstrated by other silver salt-free C(sp(3))-H bond
      arylation conditions. The synthetic utility of the method is further illustrated
      in the synthesis of the psychotropic drug phenibut. A detailed mechanism study
      has been conducted to understand the reaction pathway. 

PMID- 25763684
TI  - Learning from nature: constructing integrated graphene-based artificial nacre.
AB  - Natural nacre supplies a number of properties that can be used in designing high
      performance bioinspired materials. Likewise, due to the extraordinary properties
      of graphene, a series of bioinspired graphene-based materials have recently been
      demonstrated. Compared to other approaches for constructing graphene-based
      materials, bioinspired concepts result in high-loading graphene, and the
      resultant high-performance graphene-based artificial nacres demonstrate isotropic
      mechanical and electrical properties. In this Perspective, we describe how to
      construct integrated graphene-based artificial nacre through the synergistic
      relationship between interface interactions and building blocks. These integrated
      graphene-based artificial nacres show promising applications in many fields, such
      as aerospace, flexible supercapacitor electrodes, artificial muscle, and tissue
      engineering. 

PMID- 25763685
TI  - Wormlike micelles with photoresponsive viscoelastic behavior formed by surface
      active ionic liquid/azobenzene derivative mixed solution.
AB  - The UV-light-stimulated self-assembly behavior of a surface active ionic liquid
      (SAIL), 1-hexadecyl-3-methylimidazolium bromide (C16mimBr), with an azobenzene
      derivative, sodium azobenzene 4-carboxylate (AzoCOONa), was investigated in
      aqueous solution. The properties and structures of the aggregates, formed at a
      concentration ratio equal to 2:1 ([C16mimBr]:[AzoCOONa]), were comprehensively
      characterized by rheometer and cryogenic transmission electron microscopy.
      Initially, viscoelastic wormlike micelles with a viscosity of 0.65 Pa.s were
      constructed in the C16mimBr/AzoCOONa system. Upon irradiation by UV light (365
      nm), particularly fascinating is that the wormlike micelles become much longer
      and more entangled, exhibiting a high viscosity of 6.9 Pa.s. This can be
      attributed to photoisomerization of the AzoCOONa molecule from trans to cis form.
      It is the first time that, with exposure to UV or visible light, the aggregate
      type of the photoresponsive system has remained unchanged, with only a change of
      internal property parameters. The cation-pi interaction prevailing over the
      hydrophobic interaction and electrostatic interaction between C16mimBr and
      AzoCOONa molecules is supposed to be responsible for this peculiar phase
      behavior. The wormlike micelles constructed with the SAIL and photosensitive
      additive exhibit controllable viscoelastic behavior in the photoresponsive
      process. In addition, the average contour length of wormlike micelles was found
      to slightly decrease with the increase of temperature. We expect this system will
      receive particular attention due to its unique properties and potential
      applications in drug delivery, biochemistry, and materials science, etc. 

PMID- 25763686
TI  - AAV-8 is more efficient than AAV-9 in transducing neonatal dog heart.
AB  - Adeno-associated virus serotype-8 and 9 (AAV-8 and 9) are the leading candidate
      vectors to test bodywide neonatal muscle gene therapy in large mammals. We have
      previously shown that systemic injection of 2-2.5*10(14) viral genome (vg)
      particles/kg of AAV-9 resulted in widespread skeletal muscle gene transfer in
      newborn dogs. However, nominal transduction was observed in the heart. In
      contrast, robust expression was achieved in both skeletal muscle and heart in
      neonatal dogs with 7.14-9.06*10(14) vg particles/kg of AAV-8. To determine
      whether superior cardiac transduction of AAV-8 is because of the higher vector
      dose, we delivered 6.14*10(14) and 9.65*10(14) vg particles/kg of AAV-9 to
      newborn puppies via the jugular vein. Transduction was examined 2.5 months later.
      Consistent with our previous reports, we observed robust bodywide transduction in
      skeletal muscle. However, increased AAV dose only moderately improved heart
      transduction. It never reached the level achieved by AAV-8. Our results suggest
      that differential cardiac transduction by AAV-8 and AAV-9 is likely because of
      the intrinsic property of the viral capsid rather than the vector dose. 

PMID- 25763687
TI  - Influence of unilateral maxillary first molar extraction treatment on second and
      third molar inclination in Class II subdivision patients.
AB  - OBJECTIVE: To assess the maxillary second molar (M2) and third molar (M3)
      inclination following orthodontic treatment of Class II subdivision malocclusion
      with unilateral maxillary first molar (M1) extraction. MATERIALS AND METHODS:
      Panoramic radiographs of 21 Class II subdivision adolescents (eight boys, 13
      girls; mean age, 12.8 years; standard deviation, 1.7 years) before treatment,
      after treatment with extraction of one maxillary first molar and Begg appliances
      and after at least 1.8 years in retention were retrospectively collected from a
      private practice. M2 and M3 inclination angles (M2/ITP, M2/IOP, M3/ITP, M3/IOP),
      constructed by intertuberosity (ITP) and interorbital planes (IOP), were
      calculated for the extracted and nonextracted segments. Random effects regression
      analysis was performed to evaluate the effect on the molar angulation of
      extraction, time, and gender after adjusting for baseline measurements. RESULTS:
      Time and extraction status were significant predictors for M2 angulation. M2/ITP
      and M2/IOP decreased by 4.04 (95% confidence interval [CI]: -6.93, 1.16; P  = 
      .001) and 3.67 (95% CI: -6.76, -0.58; P  =  .020) in the extraction group
      compared to the nonextraction group after adjusting for time and gender. The
      adjusted analysis showed that extraction was the only predictor for M3 angulation
      that reached statistical significance. M3 mesial inclination increased by 7.38
      degrees  (95% CI: -11.2, -3.54; P < .001) and 7.33 degrees  (95% CI: -11.48, 
      3.19; P  =  .001). CONCLUSIONS: M2 and M3 uprighting significantly improved in
      the extraction side after orthodontic treatment with unilateral maxillary M1
      extraction. There was a significant increase in mesial tipping of maxillary
      second molar crowns over time.

PMID- 25763688
TI  - Metal-free direct 1,6- and 1,2-difunctionalization triggered by radical
      trifluoromethylation of alkenes.
AB  - A metal-free direct remote C-H functionalization triggered by radical
      trifluoromethylation of alkenes was explored, realizing highly selective 1,6
      difunctionalization of alkenes toward valuable trifluoromethyl alpha
      hydroxycarbonyl compounds. Furthermore, a metal-free direct intermolecular
      regioselective 1,2-oxytrifluoromethylation of alkenes is also disclosed. With
      Togni's reagent as both the CF3 source and oxidant, the reaction exhibits a broad
      substrate scope with excellent functionality tolerance under mild metal-free
      conditions, thus showing great potential for synthetic utility. 

PMID- 25763689
TI  - 9alpha,11beta-PGF2, a Prostaglandin D2 Metabolite, as a Marker of Mast Cell
      Activation in Bee Venom-Allergic Patients.
AB  - Mast cell (MC) mediators, among them prostaglandin D2 (PGD2) and 9alpha,11beta
      PGF2, PGD2's metabolite, play a key role in allergic reactions, including bee
      venom anaphylaxis (BVA). Assessment of these mediators has never been performed
      in BVA. The aim of the study was to assess the activation of MC during in vivo
      provocation with bee venom (BV) and to measure PGD2 and 9alpha,11beta-PGF2 in the
      course of an allergen challenge. The second aim was to determine if assessment of
      these mediators could be useful for predicting adverse events during venom
      immunotherapy (VIT). In 16 BV-VIT patients and 12 healthy subjects, levels of
      PGD2 and 9alpha,11beta-PGF2 were assessed during BV provocation by means of the
      skin chamber method. Chamber fluids, collected at 5 and 15 min, were analyzed for
      both mediators by gas chromatography mass spectrometry negative ion chemical
      ionization. BVA in comparison to non-allergic patients had a significantly higher
      ratio of 9alpha,11beta-PGF2 in allergen-challenged chambers to 9alpha,11beta-PGF2
      in allergen-free chambers after 15 min of provocation (p = 0.039). Allergen
      challenge resulted in a significant increase of 9alpha,11beta-PGF2 levels between
      5 and 15 min after provocation only in BVA patients (p < 0.05). Analysis of log
      transformed PGD2 levels showed significant difference between changes in PGD2
      concentration between BVA and healthy subjects. No study patient developed
      adverse reactions during. 9alpha,11beta-PGF2 is actively generated during the
      early allergic response to BV. Skin chamber seems to be a promising, non-invasive
      and safe model of in vivo allergen provocation in BV-allergic patients. High or
      low levels of both mediators do not predict occurrence of adverse events during
      VIT.

PMID- 25763690
TI  - Cardiolipin at the heart of stress response across kingdoms.
AB  - Cardiolipin is a key phospholipid most specifically found in the membrane of
      mitochondria in yeasts, plants, and animals. Cardiolipins are essential for the
      maintenance, the integrity, and the dynamics of mitochondria. In most eukaryotes
      mitochondria play a central role in the response and adaptation to stress
      conditions especially through their importance in the control of programmed cell
      death. To assess the impact of the absence of cardiolipin, knock-down of the
      expression of cardiolipin synthase, the last enzyme of cardiolipin synthesis
      pathway in eukaryotes has been performed in yeasts, animals, and plants. These
      studies showed that cardiolipin is not only important for mitochondrial
      ultrastructure and for the stability of respiratory complexes, but it is also a
      key player in the response to stress, the formation of reactive oxygen species,
      and the execution of programmed cell death. 

PMID- 25763691
TI  - Calcium powered phloem protein of SEO gene family "Forisome" functions in wound
      sealing and act as biomimetic smart materials.
AB  - Forisomes protein belongs to SEO gene family and is unique to Fabaceae family.
      These proteins are located in sieve tubes of phloem and function to prevent loss
      of nutrient-rich photoassimilates, upon mechanical injury/wounding. Forisome
      protein is also known as ATP independent, mechanically active proteins. Despite
      the wealth of information role of forisome in plants are not yet fully
      understood. Recent reports suggest that forisomes protein can act as ideal model
      to study self assembly mechanism for development of nanotechnological devices
      like microfluidic system application in space exploration mission. Improvement in
      micro instrument is highly demanding and has been a key technology by NASA in
      future space exploration missions. Based on its physical parameters, forisome are
      found to be ideal biomimetic materials for micro fluidic system because the
      conformational shifts can be replicated in vitro and are fully reversible over
      large number of cycles. By the use of protein engineering forisome recombinant
      protein can be tailored. Due to its unique ability to convert chemical energy
      into mechanical energy forisome has received much attention. For
      nanotechnological application and handling biomolecules such as DNA, RNA, protein
      and cell as a whole microfluidic system will be the most powerful technology. The
      discovery of new biomimetic smart materials has been a key factor in development
      of space science and its requirements in such a challenging environment. The
      field of microfludic, particularly in terms of development of its components
      along with identification of new biomimetic smart materials, deserves more
      attention. More biophysical investigation is required to characterize it to make
      it more suitable under parameters of performance. 

PMID- 25763692
TI  - Computational identification of conserved microRNAs and their targets from
      expression sequence tags of blueberry (Vaccinium corybosum).
AB  - MicroRNAs (miRNAs) are a class of endogenous, approximately 21nt in length, non
      coding RNA, which mediate the expression of target genes primarily at post
      transcriptional levels. miRNAs play critical roles in almost all plant cellular
      and metabolic processes. Although numerous miRNAs have been identified in the
      plant kingdom, the miRNAs in blueberry, which is an economically important small
      fruit crop, still remain totally unknown. In this study, we reported a
      computational identification of miRNAs and their targets in blueberry. By
      conducting an EST-based comparative genomics approach, 9 potential vco-miRNAs
      were discovered from 22,402 blueberry ESTs according to a series of filtering
      criteria, designated as vco-miR156-5p, vco-miR156-3p, vco-miR1436, vco-miR1522,
      vco-miR4495, vco-miR5120, vco-miR5658, vco-miR5783, and vco-miR5986. Based on
      sequence complementarity between miRNA and its target transcript, 34 target ESTs
      from blueberry and 70 targets from other species were identified for the vco
      miRNAs. The targets were found to be involved in transcription, RNA splicing and
      binding, DNA duplication, signal transduction, transport and trafficking, stress
      response, as well as synthesis and metabolic process. These findings will greatly
      contribute to future research in regard to functions and regulatory mechanisms of
      blueberry miRNAs. 

PMID- 25763693
TI  - Gene regulation networks generate diverse pigmentation patterns in plants.
AB  - The diversity of pigmentation patterns observed in plants occurs due to the
      spatial distribution and accumulation of colored compounds, which may also be
      associated with structural changes to the tissue. Anthocyanins are flavonoids
      that provide red/purple/blue coloration to plants, often forming complex patterns
      such as spots, stripes, and vein-associated pigmentation, particularly in
      flowers. These patterns are determined by the activity of MYB-bHLH-WDR (MBW)
      transcription factor complexes, which activate the anthocyanin biosynthesis
      genes, resulting in anthocyanin pigment accumulation. Recently, we established
      that the MBW complex controlling anthocyanin synthesis acts within a gene
      regulation network that is conserved within at least the Eudicots. This network
      involves hierarchy, reinforcement, and feedback mechanisms that allow for
      stringent and responsive regulation of the anthocyanin biosynthesis genes. The
      gene network and mobile nature of the WDR and R3-MYB proteins provide exciting
      new opportunities to explore the basis of pigmentation patterning, and to
      investigate the evolutionary history of the MBW components in land plants. 

PMID- 25763694
TI  - Identification of gravitropic response indicator genes in Arabidopsis
      inflorescence stems.
AB  - Differential organ growth during gravitropic response is caused by differential
      accumulation of auxin, that is, relative higher auxin concentration in lower
      flanks than in upper flanks of responding organs. Auxin responsive reporter
      systems such as DR5::GUS and DR5::GFP have usually been used as indicators of
      gravitropic response in roots and hypocotyls of Arabidopsis. However, in the
      inflorescence stems, the reporter systems don't work well to monitor gravitropic
      response. Here, we aim to certify appropriate gravitropic response indicators
      (GRIs) in inflorescence stems. We performed microarray analysis comparing gene
      expression profiles between upper and lower flanks of Arabidopsis inflorescence
      stems after gravistimulation. Thirty genes showed > 2-fold differentially
      increased expression in lower flanks at 30 min, of which 19 were auxin response
      genes. We focused on IAA5 and IAA2 and verified whether they are appropriate GRIs
      by real-time qRT-PCR analyses. Transcript levels of IAA5 and IAA2 were remarkably
      higher in lower flanks than in upper flanks after gravistimulation. The biased
      IAA5 or IAA2 expression is disappeared in sgr2-1 mutant which is defective in
      gravity perception, indicating that gravity perception process is essential for
      formation of the biased gene expression during gravitropism. IAA5 expression was
      remarkably increased in lower flanks at 30 min after gravistimulation, whereas
      IAA2 expression was gradually decreased in upper flanks in a time-dependent
      manner. Therefore, we conclude that IAA5 is a sensitive GRI to monitor asymmetric
      auxin signaling caused by gravistimulation in Arabidopsis inflorescence stems. 

PMID- 25763695
TI  - Histidine promotes the loading of nickel and zinc, but not of cadmium, into the
      xylem in Noccaea caerulescens.
AB  - Histidine is known to be involved in Ni hyperaccumulation. Recently, histidine
      dependent xylem loading of Ni and Zn has been demonstrated in the Zn/Ni/Cd
      hyperaccumulator, Noccaea caerulescens. Here we tested the hypothesis whether Cd
      xylem loading is histidine-dependent, too. In contrast to that of Ni and Zn, the
      xylem loading of Cd was not affected by exogenous histidine. Histidine
      accumulation in root cells appears to facilitate the radial transport of Ni and
      Zn, but not Cd, across the roots. This may be due to the relatively high
      preference of Cd for coordination with sulfur over coordination with nitrogen, in
      comparison with Ni and Zn. 

PMID- 25763696
TI  - Uncertain role of MtSEO-F3 in assembly of Medicago truncatula forisomes.
AB  - Forisomes are specialized multimeric protein complexes found only in the
      papilionoid legumes. They undergo a reversible conformational change in response
      to phloem injury to enable the occlusion of sieve tubes, thus preventing the loss
      of photoassimilates. The individual subunits are designated by the letters SEO-F
      (sieve element occlusion by forisomes) and are part of the larger SEO protein
      family, which also includes the typical P-proteins found in most dicots and some
      monocots. When specific SEO-F subunits from different species are expressed in a
      heterologous background, they self-assemble into fully-functional artificial
      forisomes. However, with the exception of basal species such as Dipteryx
      panamensis, the geometry of these artificial forisomes differs from that of their
      native counterparts. Studies involving SEO-F proteins from the model legume
      Medicago truncatula have shown that a combination of 3 of the 4 subunits can fine
      tune the geometry of artificial forisomes. However, MtSEO-F3 was excluded from
      these studies because it was not incorporated into either the native or
      artificial forisomes in our original experiments. In this addendum, we present
      further data concerning the interactive properties of the SEO-F proteins and
      confirm that all 4 MtSEO-F proteins interact in all possible pairwise
      combinations. These data indicate that the exclusion of MtSEO-F3 from the compact
      forisome may reflect the steric hindrance of binding sites rather than an
      inability to interact with other forisome subunits. 

PMID- 25763697
TI  - Common and divergent roles of plant hormones in nodulation and arbuscular
      mycorrhizal symbioses.
AB  - All of the classical plant hormones have been suggested to influence nodulation,
      including some that interact with the Autoregulation of Nodulation (AON) pathway.
      Leguminous plants strictly regulate the number of nodules formed through this AON
      pathway via a root-shoot-root loop that acts to suppress excessive nodulation. A
      related pathway, the Autoregulation of Mycorrhization (AOM) pathway controls the
      more ancient, arbuscular mycorrhizal (AM) symbiosis. A comparison of the
      published responses to the classical hormones in these 2 symbioses shows that
      most influence the symbioses in the same direction. This may be expected if they
      affect the symbioses via common components of these symbiotic regulatory
      pathways. However, some hormones influence these symbioses in opposite
      directions, suggesting a more complex relationship, and probably one that is not
      via the common components of these pathways. In a recent paper we showed, using a
      genetic approach, that strigolactones and brassinosteroids do not act downstream
      of the AON genes examined and argued that they probably act independently to
      promote nodule formation. Recently it has been shown that the control of
      nodulation via the AON pathway involves mobile CLE peptide signals. It is
      therefore suggested that a more direct avenue to determine if the classical
      hormones play a direct role in the autoregulatory pathways is to further examine
      whether CLE peptides and other components of these processes can influence, or be
      influenced by, the classical hormones. Such studies and other comparisons between
      the nodulation and mycorrhizal symbioses should allow the role of the classical
      hormones in these critical symbioses to be rapidly advanced. 

PMID- 25763698
TI  - Cloning and functional characterization of the promoter of PsSEOF1 gene from
      Pisum sativum under different stress conditions using Agrobacterium-mediated
      transient assay.
AB  - PsSEOF1, a SEO (sieve element occlusion) gene family protein (forisome) is
      calcium powered motor protein and is located close to plasma membrane of sieve
      element. In sieve element (SE) it senses the calcium ion levels and undergoes ATP
      independent conformational shifts. Forisome, meaning gate-bodies (Latin foris:
      wing of a gate; Greek soma: body). Recent reports show that SEO gene family
      protein can prevent the loss of nutrient rich photoassimilate upon wound injury.
      The regulation of SEO protein forisome under abiotic/ biotic stress is still
      unknown. The analysis of cis-regulatory element present in the upstream region is
      not well understood. Tissue specific promoters guarantee correct expression when
      it perceives particular stimuli. Here we report isolation of tissue specific
      promoter of PsSEOF1 was isolated by gene walking PCR from P. sativum (pea)
      genomic DNA library constructed by BD genome walker kit. In silico analysis
      revealed several putative cis element within this promoter sequence like wound
      response, cold, dehydration. Putative elements which might be required for its
      vascular tissue specificity has also been identified. The GUS activities of
      PsSEOF1 promoter-GUS chimeric construct in the agroinfiltrated leaves under
      different environmental stress abiotic and biotic like wound, cold, salt and
      phytohormones has shown high level of GUS activity. To identify the activity of
      PsSEOF1 promoter under different stress condition an Agrobacterium-mediated
      transient expression of tobacco plants were subjected to histochemical GUS
      staining. Stress-inducible nature of PsSEOF1 promoter opens possibility for the
      study of the PsSEOF1 gene regulation under stress condition. The isolated
      promoter sequence could serve as an important candidate for tissue specific
      promoter in genetic engineering of plant under stress conditions. 

PMID- 25763699
TI  - Microsome-associated proteome modifications of Arabidopsis seedlings grown on
      board the International Space Station reveal the possible effect on plants of
      space stresses other than microgravity.
AB  - Growing plants in space for using them in bioregenerative life support systems
      during long-term human spaceflights needs improvement of our knowledge in how
      plants can adapt to space growth conditions. In a previous study performed on
      board the International Space Station (GENARA A experiment STS-132) we evaluate
      the global changes that microgravity can exert on the membrane proteome of
      Arabidopsis seedlings. Here we report additional data from this space experiment,
      taking advantage of the availability in the EMCS of a centrifuge to evaluate the
      effects of cues other than microgravity on the relative distribution of membrane
      proteins. Among the 1484 membrane proteins quantified, 227 proteins displayed no
      abundance differences between u g and 1 g in space, while their abundances
      significantly differed between 1 g in space and 1 g on ground. A majority of
      these proteins (176) were over-represented in space samples and mainly belong to
      families corresponding to protein synthesis, degradation, transport, lipid
      metabolism, or ribosomal proteins. In the remaining set of 51 proteins that were
      under-represented in membranes, aquaporins and chloroplastic proteins are
      majority. These sets of proteins clearly appear as indicators of plant
      physiological processes affected in space by stressful factors others than
      microgravity. 

PMID- 25763700
TI  - Phospholipid biosynthesis increases in RHD3-defective mutants.
AB  - RHD3, a member of the ER-shaping dynamin-like GTPases, is required in the
      transition from a cisternal to a tubular ER architecture during cell growth. The
      aberrant ER morphology in rhd3 mutants may be correlated with alterations of the
      ER lipid bilayer. We analyzed the lipid fraction of rhd3 mutants at qualitative
      and quantitative levels. We observed an increase of the amount of phospholipids
      but also of proteins in the mutants, indicating an overall increase of ER
      membranes. This increase may indicate that phospholipid biosynthesis is
      deregulated in rhd3 mutants. It was shown that overexpression of PIS1 and PIS2
      (involved in phosphatidylinositol biosynthesis) induces the synthesis of
      phosphatidylinositol (PI) but also of phosphatidic acid and that overexpression
      of PIS1 also induces the synthesis of phosphatidylethanolamine and
      diacylglycerol. (1) We wondered whether PIS1 or PIS2 could be linked to the
      increase of the amount of phospholipids in rhd3 mutants. To answer, we measured
      the phospholipid composition in the double mutants rhd3-7/pis1 and rhd3-7/pis2.
      The phospholipid increase in the rhd3 mutant was compensated in rhd3-7/pis1 but
      not rhd3-7/pis2. Our results suggest a possible deregulation of PIS1 in the rhd3
      mutant. 

PMID- 25763701
TI  - Exogenous application of histone demethylase inhibitor trans-2
      phenylcyclopropylamine mimics FLD loss-of-function phenotype in terms of systemic
      acquired resistance in Arabidopsis thaliana.
AB  - Plants often learn from previous infections to mount higher level of resistance
      during subsequent infections, a phenomenon referred to as systemic acquired
      resistance (SAR). During primary infection, mobile signals generated at the
      infection site subsequently move to the rest of plant to activate SAR. SAR
      activation is associated with alteration in the nucleosomal composition at the
      promoters of several defense-related genes. However, genetic regulations of such
      epigenetic modifications are largely obscure. Recently, we have demonstrated that
      Reduced Systemic immunity1/FLOWERING LOCUS D (RSI1; alias FLD) a homolog of human
      histone demethylase, is required for SAR development in Arabidopsis. Here, we
      report that exogenous application of a histone demethylase inhibitor trans-2
      phenylcyclopropylamine (2-PCPA) mimics rsi1/fld loss-of-function phenotypes in
      terms of SAR and associated histone demethylation at the promoters of PR1, WRKY
      29, and WRKY6 genes, and as well as flowering phenotypes. Our results suggest
      histone demethylase activity of FLD is important for controlling SAR activation. 

PMID- 25763702
TI  - Spatio-temporal distribution patterns of GRF-INTERACTING FACTOR expression and
      leaf size control.
AB  - Developmental biologists have been fascinated with the long-standing mystery of
      how multicellular organisms, such as plants and animals, sense and control their
      organ size. In plants, leaves are a suitable experimental system for elucidation
      of the mystery, because they, like animal organs, inherently exhibit a
      determinate growth pattern, meaning that they possess genetic information for the
      control of their final size. The cell proliferation and expansion processes are
      prerequisites for growth, so that the genetic controls should converge on the 2
      cellular processes and decide their rate or duration during leaf growth. Plant
      scientists have found dozens of genes involved in the control of the cellular
      processes, including the Arabidopsis thaliana GRF-INTERACTING FACTOR (GIF)
      family. The GIF family consists of 3 members, GIF1 to GIF3, and encodes a class
      of transcription co-activators. Although the GIF family genes have been shown to
      play an essential role in the control of cell proliferation of the leaf organ,
      understanding of the spatio-temporal behaviors of GIF expression, in both aspects
      of their promoters and proteins, has been limited to GIF1 (also known as
      ANGUSTIFOLIA3, AN3). Here, we define kinematic growth properties of wild-type and
      gif leaf organs and present spatio-temporal expression patterns of all GIF genes,
      thus providing comprehensive insights into biological roles and expression
      behaviors of the whole GIF family members during leaf growth. 

PMID- 25763703
TI  - Alpine scree plants benefit from cryptic coloration with limited cost.
AB  - Like animals, plants are attacked by enemies (herbivores) that forage using
      visual cues; however, the defensive coloration type known as cryptic coloration
      was rarely reported in plants. For most autotrophic plants, because
      photosynthesis relies on the presence of chlorophyll, a green leaf appearance is
      standard. However, if having leaves that are not green is more beneficial than
      costly, such coloration may evolve under certain conditions. Taking advantage of
      the leaf color dimorphism of Corydalis benecincta, we showed that the cryptically
      colored leaves confer a clear benefit without obvious cost in natural
      populations. Based on this study, we try to provide a framework on which to base
      a cost-benefit analysis to investigate the evolution of cryptic leaf coloration
      in plants. 

PMID- 25763704
TI  - AtFtsH4 perturbs the mitochondrial respiratory chain complexes and auxin
      homeostasis in Arabidopsis.
AB  - Mitochondrial AtFtsH4 protease is one of four inner membrane-bound FtsH proteases
      in Arabidopsis. We found that the loss of AtFtsH4 regulates Arabidopsis
      development and architecture by mediating the peroxidase-dependent interplay
      between hydrogen peroxide (H2O2) and auxin homeostasis. These morphological
      changes were correlated with elevated levels of both hydrogen peroxide and
      peroxidases, which suggested that ftsh4-4 plant was related to the oxidative
      stress, and that the architecture was caused by the auxin homeostasis
      perturbation. This view was supported by the expression levels of several auxin
      signaling genes and auxin binding and transport genes were decreased
      significantly in ftsh4-4 plants. Taken together, our data published in the May
      issue of Molecular Plant suggests a link between the lack of AtFtsH4 protease,
      oxidative stress,s and auxin homeostasis to regulate plant growth and
      development. However, the detail molecular mechanisms of AtFtSH4 regulating
      oxidation stress and auxin homeostasis is unclear. Here, we present evidence that
      the high level accumulated of H2O2 in ftsh4-4 may correlates with the decreased
      mitochondrial respiration genes. We also showed that the decreased auxin level
      and auxin transport may caused by the inhibition of mitochondrial respiratory
      chain complexes. 

PMID- 25763705
TI  - Diurnal and circadian expression profiles of glycerolipid biosynthetic genes in
      Arabidopsis.
AB  - Glycerolipid composition in plant membranes oscillates in response to diurnal
      change. However, its functional significance remained unclear. A recent discovery
      that Arabidopsis florigen FT binds diurnally oscillating phosphatidylcholine
      molecules to promote flowering suggests that diurnal oscillation of glycerolipid
      composition is an important input in flowering time control. Taking advantage of
      public microarray data, we globally analyzed the expression pattern of
      glycerolipid biosynthetic genes in Arabidopsis under long-day, short-day, and
      continuous light conditions. The results revealed that 12 genes associated with
      glycerolipid metabolism showed significant oscillatory profiles. Interestingly,
      expression of most of these genes followed circadian profiles, suggesting that
      glycerolipid biosynthesis is partially under clock regulation. The oscillating
      expression profile of one representative gene, PECT1, was analyzed in detail.
      Expression of PECT1 showed a circadian pattern highly correlated with that of the
      clock-regulated gene GIGANTEA. Thus, our study suggests that a considerable
      number of glycerolipid biosynthetic genes are under circadian control. 

PMID- 25763706
TI  - Root development under control of magnesium availability.
AB  - Roots are reported to be plastic in response to nutrient supply, but relatively
      little is known about their development in response to magnesium (Mg)
      availability. Here, we showed the influence of both low and high Mg availability
      on the development of roots including root hairs and highlighted insights into
      the regulatory role of Mg availability on root hair development and its mechanism
      in Arabidopsis with combining our published research. Mg concentration in roots
      decreased quickly after the removal of Mg from the nutrient solution and
      increased progressively with increasing exogenous Mg supply in the media.
      However, transcriptome analysis suggested that Mg starvation did not alter the
      expression of most genes potentially involved in the transport. Primary root
      elongation and lateral root formation in Arabidopsis were not influenced by low
      Mg but inhibited by high Mg after one-week period. Moreover, low Mg availability
      significantly increased but high Mg reduced the initiation, density and length of
      root hairs, which through the characterized Ca(2+) and ROS signal transduction
      pathways. More physiological mechanisms underlying Mg-regulated root development
      remain to be elucidated in future researches. 

PMID- 25763707
TI  - DELLA and SCL3 balance gibberellin feedback regulation by utilizing INDETERMINATE
      DOMAIN proteins as transcriptional scaffolds.
AB  - DELLA proteins are key negative regulators in the phytohormone gibberellin's (GA)
      signaling. In addition to this role, the DELLA proteins upregulate the gene
      expression levels of the positive regulators in GA signaling, such as GA 20
      oxidase, GA receptor, and a transcriptional regulator, SCARECROW-LIKE3 (SCL3),
      which enables the regulation of GA feedback. Since DELLAs lack a known DNA
      binding domain, other transcription factor(s) that recruit DELLAs to DNA are
      essential for this regulation. Recently, we showed that the INDETERMINATE DOMAIN
      family proteins serve as transcriptional scaffolds to exert the transactivation
      activity of DELLAs. This finding and further analyses regarding the function of
      SCL3 indicate that the balance of the DELLAs and SCL3 protein levels (both are
      GRAS proteins) regulates downstream gene expression through IDDs binding to DNA.
      Here, we review the regulatory system in plants similar to ours and also discuss
      the interactive network between GRAS and IDD proteins. 

PMID- 25763708
TI  - Membrane-triggered plant immunity.
AB  - Plants have evolved sophisticated defense mechanisms to resist pathogen invasion.
      Upon the pathogen recognition, the host plants activate a variety of signal
      transduction pathways, and one of representative defense responses is systemic
      acquired resistance (SAR) that provides strong immunity against secondary
      infections in systemic tissues. Accumulating evidence has demonstrated that
      modulation of membrane composition contributes to establishing SAR and disease
      resistance in Arabidopsis, but underlying molecular mechanisms remain to be
      elucidated. Here, we show that a membrane-bound transcription factor (MTF) is
      associated with plant responses to pathogen attack. The MTF is responsive to
      microbe-associated molecular pattern (MAMP)-triggered membrane rigidification at
      the levels of transcription and proteolytic processing. The processed nuclear
      transcription factor possibly regulates pathogen resistance by directly
      regulating PATHOGENESIS-RELATED (PR) genes. Taken together, our results suggest
      that pathogenic microorganisms trigger changes in physico-chemical properties of
      cellular membrane in plants, and the MTF conveys the membrane information to the
      nucleus to ensure prompt establishment of plant immunity. 

PMID- 25763709
TI  - CAM7 and HY5 genetically interact to regulate root growth and abscisic acid
      responses.
AB  - CAM7, a member of CaM family in Arabidopsis, acts as a transcriptional regulator
      and enhances photomorphogenic growth and light regulated gene expression under
      various light conditions. HY5, a bZIP transcription factor, promotes
      photomorphogenesis at multiple wavelengths of light including far red, red, and
      blue light. Very recently, it has been shown that CAM7 and HY5 directly interact
      with the HY5 promoter to regulate the transcriptional activity of HY5 during
      Arabidopsis seedling development. In this study, we have investigated the root
      phenotype of cam7 hy5 double mutants and shown that CAM7 and HY5 genetically
      interact to control the root growth. We have further shown an interdependent
      function of HY5 and CAM7 in abscisic acid (ABA) responsiveness. 

PMID- 25763710
TI  - Divergent evolution of potato immune receptor CC domain interactions with the Ran
      GTPase-activating protein 2.
AB  - Effector-triggered immunity mediated by immune receptors in plants provides
      powerful defense against specific pathogens. Solanum tuberosum Ran GTPase
      Activating Protein 2 (StRanGAP2) interacts with immune receptors Rx and Gpa2
      through their coiled-coil (CC) domains. We assayed additional CC domains from
      other Solanaceous immune receptors and observed interaction by co
      immunoprecipitation between StRanGAP2 and a novel immune receptor, STR5. A CC
      domain very similar to Rx and Gpa2, STR4, failed to interact, likely due to
      sequence divergence in the region implicated in StRanGAP2 binding. Like Rx and
      Gpa2, STR5 interacted with the StRanGAP2 N-terminal WPP domain. Our findings
      substantiate the importance of RanGAPs as common CC-interacting proteins of
      multiple immune receptors requiring further study to define their roles in
      pathogen perception. 

PMID- 25763711
TI  - POLYAMINE OXIDASE 1 from rice (Oryza sativa) is a functional ortholog of
      Arabidopsis POLYAMINE OXIDASE 5.
AB  - POLYAMINE OXIDASE 1 (OsPAO1), from rice (Oryza sativa), and POLYAMINE OXIDASE 5
      (AtPAO5), from Arabidopsis (Arabidopsis thaliana), are enzymes sharing high
      identity at the amino acid level and with similar characteristics, such as
      polyamine specificity and pH preference; furthermore, both proteins localize to
      the cytosol. A loss-of-function Arabidopsis mutant, Atpao5-2, was hypersensitive
      to low doses of exogenous thermospermine but this phenotype could be rescued by
      introduction of the wild-type AtPAO5 gene. Introduction of OsPAO1, under the
      control of a constitutive promoter, into Atpao5-2 mutants also restored normal
      thermospermine sensitivity, allowing growth in the presence of low levels of
      thermospermine, along with a concomitant decrease in thermospermine content in
      plants. By contrast, introduction of OsPAO3, which encodes a peroxisome-localized
      polyamine oxidase, into Atpao5-2 plants could not rescue any of the mutant
      phenotypes in the presence of thermospermine. These results suggest that OsPAO1
      is the functional ortholog of AtPAO5. 

PMID- 25763712
TI  - First-Trimester Placental and Myometrial Blood Perfusion Measured by Three
      Dimensional Power Doppler in Preeclampsia.
AB  - OBJECTIVE: The study aims to evaluate first-trimester vascularization of the
      placenta and subplacental myometrium in women who subsequently develop
      preeclampsia. STUDY DESIGN: A case-control study nested in a prospective cohort
      was conducted in women with singleton pregnancy between 11 and 14 weeks'
      gestation. Three-dimensional standardized acquisition of the placenta and
      subplacental myometrium volumes with and without power Doppler was undertaken,
      and all participants were followed up until delivery. Each woman diagnosed with
      preeclampsia was matched with three controls who delivered at term without
      pregnancy complications. First-trimester volume, vascularization index (VI), flow
      index (FI), and vascular flow index (VFI) of the entire placenta and subplacental
      myometrium were measured separately. The results were stratified for preterm and
      term preeclampsia, respectively. RESULTS: A total of 1,034 women were recruited,
      including 16 (1.5%) who developed term preeclampsia and 4 (0.4%) who developed
      preterm preeclampsia. Preeclampsia was associated with a significantly lower
      placental VI, placental VFI, subplacental VI, and subplacental VFI in the first
      trimester than with the controls (all p < 0.05). All cases (4/4) of preterm
      preeclampsia, 56% (9/16) of term preeclampsia, and 28% (17/60) of the controls
      had a subplacental VI below 18% (p < 0.01). CONCLUSION: First-trimester placental
      and subplacental myometrium vascularizations are significantly reduced in women
      who subsequently develop preeclampsia.

PMID- 25763713
TI  - Equipoise in Research and the Development of Neonatal Interventions for the
      Management of Respiratory Distress Syndrome: A Historical Perspective.
AB  - The historical review of how evidence was developed for the management of
      respiratory distress syndrome in premature infants has not been clearly
      characterized. Knowledge of this process is essential to understand the role of
      equipoise and its influence on the decision to evaluate interventions as they
      were implemented in the practice of medicine. We suspect that errant approaches
      to clinical equipoise secondary to states of false certainty and false
      uncertainty have been important barriers to the timely acquisition and
      implementation of evidence-based knowledge necessary to improve outcomes in this
      fragile population of infants. When confronted with the decision to test an
      intervention, physicians should question whether they have lost clinical
      equipoise based on opinion, expertise, or observational data rather than evidence
      obtained from methodological inquiry; doing so facilitates reaching clinical
      equipoise and promotes the application of scientific methodology to answer
      relevant clinical questions. Timely acquisition of evidence-based knowledge can
      be viewed as an ethical imperative when the status quo may have negative
      consequences on outcomes for generations. 

PMID- 25763714
TI  - A unique, highly conserved secretory invertase is differentially expressed by
      promastigote developmental forms of all species of the human pathogen,
      Leishmania.
AB  - Leishmania are protozoan pathogens of humans that exist as extracellular
      promastigotes in the gut of their sand fly vectors and as obligate intracellular
      amastigotes within phagolysosomes of infected macrophages. Between infectious
      blood meal feeds, sand flies take plant juice meals that contain sucrose and
      store these sugars in their crop. Such sugars are regurgitated into the sand fly
      anterior midgut where they impact the developing promastigote parasite
      population. In this report we showed that promastigotes of all Leishmania species
      secreted an invertase/sucrase enzyme during their growth in vitro. In contrast,
      neither L. donovani nor L. mexicana amastigotes possessed any detectable
      invertase activity. Importantly, no released/secreted invertase activity was
      detected in culture supernatants from either Trypanosoma brucei or Trypanosoma
      cruzi. Using HPLC, the L. donovani secretory invertase was isolated and subjected
      to amino acid sequencing. Subsequently, we used a molecular approach to identify
      the LdINV and LmexINV genes encoding the ~72 kDa invertases produced by these
      organisms. Interestingly, we identified high fidelity LdINV-like homologs in the
      genomes of all Leishmania sp. but none were present in either T. brucei or T.
      cruzi. Northern blot and RT-PCR analyses showed that these genes were
      developmentally/differentially expressed in promastigotes but not amastigotes of
      these parasites. Homologous transfection studies demonstrated that these genes in
      fact encoded the functional secretory invertases produced by these parasites.
      Cumulatively, our results suggest that these secretory enzymes play critical
      roles in the survival/growth/development and transmission of all Leishmania
      parasites within their sand fly vector hosts.

PMID- 25763716
TI  - Differences in spirometry interpretation algorithms: influence on decision making
      among primary-care physicians.
AB  - BACKGROUND: Spirometry is recommended for the diagnosis of asthma and chronic
      obstructive pulmonary disease (COPD) in international guidelines and may be
      useful for distinguishing asthma from COPD. Numerous spirometry interpretation
      algorithms (SIAs) are described in the literature, but no studies highlight how
      different SIAs may influence the interpretation of the same spirometric data.
      AIMS: We examined how two different SIAs may influence decision making among
      primary-care physicians. METHODS: Data for this initiative were gathered from 113
      primary-care physicians attending accredited workshops in Canada between 2011 and
      2013. Physicians were asked to interpret nine spirograms presented twice in
      random sequence using two different SIAs and touch pad technology for anonymous
      data recording. RESULTS: We observed differences in the interpretation of
      spirograms using two different SIAs. When the pre-bronchodilator FEV1/FVC (forced
      expiratory volume in one second/forced vital capacity) ratio was >0.70, algorithm
      1 led to a 'normal' interpretation (78% of physicians), whereas algorithm 2
      prompted a bronchodilator challenge revealing changes in FEV1 that were
      consistent with asthma, an interpretation selected by 94% of physicians. When the
      FEV1/FVC ratio was <0.70 after bronchodilator challenge but FEV1 increased >12%
      and 200 ml, 76% suspected asthma and 10% suspected COPD using algorithm 1,
      whereas 74% suspected asthma versus COPD using algorithm 2 across five separate
      cases. The absence of a post-bronchodilator FEV1/FVC decision node in algorithm 1
      did not permit consideration of possible COPD. CONCLUSIONS: This study suggests
      that differences in SIAs may influence decision making and lead clinicians to
      interpret the same spirometry data differently.

PMID- 25763717
TI  - Editor's recognition awards.

PMID- 25763715
TI  - Hydrogen sulfide mitigates homocysteine-mediated pathological remodeling by
      inducing miR-133a in cardiomyocytes.
AB  - An elevated level of homocysteine called hyperhomocysteinemia (HHcy) is
      associated with pathological cardiac remodeling. Hydrogen sulfide (H2S) acts as a
      cardioprotective gas; however, the mechanism by which H2S mitigates homocysteine
      mediated pathological remodeling in cardiomyocytes is unclear. We hypothesized
      that H2S ameliorates HHcy-mediated hypertrophy by inducing cardioprotective miR
      133a in cardiomyocytes. To test the hypothesis, HL1 cardiomyocytes were treated
      with (1) plain medium (control, CT), (2) 100 uM of homocysteine (Hcy), (3) Hcy
      with 30 uM of H2S (Hcy + H2S), and (4) H2S for 24 h. The levels of hypertrophy
      markers: c-fos, atrial natriuretic peptide (ANP), and beta-myosin heavy chain
      (beta-MHC), miR-133a, and its transcriptional inducer myosin enhancer factor-2C
      (MEF2C) were determined by Western blotting, RT-qPCR, and immunofluorescence. The
      activity of MEF2C was assessed by co-immunoprecipitation of MEF2C with histone
      deacetylase-1(HDAC1). Our results show that H2S ameliorates homocysteine-mediated
      up-regulation of c-fos, ANP, and beta-MHC, and down-regulation of MEF2C and miR
      133a. HHcy induces the binding of MEF2C with HDAC1, whereas H2S releases MEF2C
      from MEF2C-HDAC1 complex causing activation of MEF2C. These findings elicit that
      HHcy induces cardiac hypertrophy by promoting MEF2C-HDAC1 complex formation that
      inactivates MEF2C causing suppression of anti-hypertrophy miR-133a in
      cardiomyocytes. H2S mitigates hypertrophy by inducing miR-133a through activation
      of MEF2C in HHcy cardiomyocytes. To our knowledge, this is a novel mechanism of
      H2S-mediated activation of MEF2C and induction of miR-133a and inhibition of
      hypertrophy in HHcy cardiomyocytes.

PMID- 25763718
TI  - Mammographic breast density: impact on breast cancer risk and implications for
      screening.
AB  - Mammographic breast density is rapidly becoming a hot topic in both the medical
      literature and the lay press. In the United States, recent legislative changes in
      19 states now require radiologists to notify patients regarding breast density as
      well as the possible need for supplemental screening. Federal legislation
      regarding breast density notification has been introduced, and its passage is
      likely on the horizon. An understanding of the context, scientific evidence, and
      controversies surrounding the topic of breast density as a risk factor for breast
      cancer is critical for radiologists. The current state of evidence is presented
      regarding supplemental screening for women with dense breasts, including the use
      of digital breast tomosynthesis, whole-breast ultrasonography, and gadolinium
      enhanced magnetic resonance imaging. A review of current practice guidelines and
      additional sources of information will improve radiologists' understanding of the
      relevant subject of breast density and enable them to respond appropriately to
      questions from patients, clinicians, and the media.

PMID- 25763719
TI  - Breast density: clinical implications and assessment methods.
AB  - Breast density assessment is an important component of the screening mammography
      report and conveys information to referring clinicians about mammographic
      sensitivity and the relative risk for developing breast cancer. These topics have
      gained substantial attention because of recent legislation in several states that
      requires patients to be informed of dense breast tissue and the potential for
      associated breast cancer risk and decreased mammographic sensitivity. Because of
      the considerable implications of diagnosing a woman with dense breast tissue,
      radiologists should strive to be as consistent as possible when assessing breast
      density. Commonly used methods of breast density assessment range from subjective
      visual estimation to quantitative calculations of area and volume density
      percentages made with complex computer algorithms. The basic principles of
      currently available commercial methods of calculating fibroglandular density are
      described and illustrated. There is no criterion standard for determining breast
      density, but understanding the pros and cons of the various assessment methods
      will allow radiologists to make informed decisions. Radiologists should
      understand the basic factors involved in breast density assessment, the changes
      related to density assessment described in the fifth edition of the American
      College of Radiology Breast Imaging Reporting and Data System (BI-RADS) lexicon,
      and the capabilities of currently available software. Online supplemental
      material is available for this article.

PMID- 25763720
TI  - Invited commentary: The breast density dilemma--challenges, lessons, and future
      directions.

PMID- 25763721
TI  - Building a bridge to save a failing ventricle: radiologic evaluation of short-
      and long-term cardiac assist devices.
AB  - Heart failure is recognized with increasing frequency worldwide and often
      progresses to an advanced refractory state. Although the reference standard for
      treatment of advanced heart failure remains cardiac transplantation, the
      increasing shortage of donor organs and the unsuitability of many patients for
      transplantation surgery has led to a search for alternative therapies. One such
      therapy is mechanical circulatory support, which helps relieve the load on the
      ventricle and thereby allows it to recover function. In addition, there is
      increasing evidence supporting the use of mechanical devices as a bridge to
      recovery in patients with acute refractory heart failure. In this article, the
      imaging evaluation of various commonly used short- and long-term cardiac assist
      devices is discussed, and their relevant mechanisms of action and physiology are
      described. Imaging, particularly computed tomography (CT), plays a crucial role
      in preoperative evaluation for assessment of candidacy for implantation of a left
      ventricular assist device (LVAD) or total artificial heart (TAH). Also,
      echocardiography and CT are indispensable in assessment of complications
      associated with cardiac devices. Complications commonly associated with short
      term assist devices include bleeding and malpositioning, whereas long-term
      devices such as LVADs may be associated with infection, pump thrombosis, and
      cannula malfunction, as well as bleeding. CT is also commonly performed for
      preoperative planning before LVAD or TAH explantation, replacement of a device or
      one of its components, and cardiac transplantation. Online supplemental material
      is available for this article.

PMID- 25763722
TI  - Histiocytic disorders of the chest: imaging findings.
AB  - Histiocytic disorders of the chest comprise a broad spectrum of diseases. The
      lungs may be involved in isolation or as part of systemic disease. Some of these
      disorders are primary and have unknown etiology, and others result from a
      histiocytic response to a known cause. Among primary histiocytic disorders,
      pulmonary Langerhans cell histiocytosis (PLCH) is the most common; others include
      Erdheim-Chester disease and Rosai-Dorfman disease. Adult PLCH occurs almost
      exclusively in adults aged 20-40 years who smoke. Pediatric PLCH is extremely
      rare and typically occurs as part of multisystemic disease. Erdheim-Chester
      disease affects middle-aged and older adults; thoracic involvement usually occurs
      as part of systemic disease. Rosai-Dorfman disease affects children and young
      adults and manifests as painless cervical lymphadenopathy. Examples of secondary
      histiocytic disorders are storage diseases such as Gaucher disease, Niemann-Pick
      disease, and Fabry disease; pneumoconiosis such as silicosis and coal workers'
      pneumoconiosis; and infections such as Whipple disease and malakoplakia. These
      disorders are characterized at histopathologic examination on the basis of
      infiltration of alveoli or the pulmonary interstitium by histiocytes, which are a
      group of cells that includes macrophages and dendritic cells. Dendritic cells are
      a heterogeneous group of nonphagocytic antigen-presenting immune cells.
      Immunohistochemical markers help to distinguish among various primary histiocytic
      disorders. Characteristic radiologic findings in the appropriate clinical context
      may obviate biopsy to establish a correct diagnosis. However, in the absence of
      these findings, integration of clinical, pathologic, and radiologic features is
      required to establish a diagnosis.

PMID- 25763723
TI  - Infiltrative hepatocellular carcinoma: what radiologists need to know.
AB  - Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related
      death worldwide. The macroscopic growth pattern of HCC is subdivided into three
      categories: nodular, massive, and infiltrative. Infiltrative HCC accounts for 7%
      20% of HCC cases and is confirmed at pathologic analysis on the basis of the
      spread of minute tumor nodules throughout large regions of the liver.
      Infiltrative HCC may represent a diagnostic challenge because it is often
      difficult to distinguish from background changes in cirrhosis at imaging.
      Infiltrative HCC usually spreads over multiple hepatic segments, occupying an
      entire hepatic lobe or the entire liver, and it is frequently associated with
      portal vein tumor thrombosis. The tumor is usually ill defined at ultrasonography
      and shows minimal and inconsistent arterial enhancement and heterogeneous washout
      at contrast material-enhanced computed tomography and magnetic resonance (MR)
      imaging. The tumor may be more visible among the surrounding liver parenchyma at
      diffusion-, T1-, and T2-weighted MR imaging. Several liver diseases can mimic the
      infiltrative appearance of this malignancy, including focal confluent fibrosis,
      hepatic fat deposition, hepatic microabscesses, intrahepatic cholangiocarcinoma,
      and diffuse metastatic disease (pseudocirrhosis). The prognosis for patients with
      infiltrative HCC is poor because the tumor is often markedly advanced and
      associated with vascular invasion at presentation. Survival after surgical
      resection is decreased; thus, infiltrative HCC is a contraindication for
      resection and transplantation. Knowledge of the key tumor characteristics and
      imaging findings will help radiologists formulate a correct and timely diagnosis
      to improve patient management.

PMID- 25763724
TI  - Polypoid lesions of the gallbladder: disease spectrum with pathologic
      correlation.
AB  - Gallbladder polyps are seen on as many as 7% of gallbladder ultrasonographic
      images. The differential diagnosis for a polypoid gallbladder mass is wide and
      includes pseudotumors, as well as benign and malignant tumors. Tumefactive sludge
      may be mistaken for a gallbladder polyp. Pseudotumors include cholesterol polyps,
      adenomyomatosis, and inflammatory polyps, and they occur in that order of
      frequency. The most common benign and malignant tumors are adenomas and primary
      adenocarcinoma, respectively. Polyp size, shape, and other ancillary imaging
      findings, such as a wide base, wall thickening, and coexistent gallstones, are
      pertinent items to report when gallbladder polyps are discovered. These findings,
      as well as patient age and risk factors for gallbladder cancer, guide clinical
      decision making. Symptomatic polyps without other cause for symptoms, an age over
      50 years, and the presence of gallstones are generally considered indications for
      cholecystectomy. Incidentally noted pedunculated polyps smaller than 5 mm
      generally do not require follow-up. Polyps that are 6-10 mm require follow-up,
      although neither the frequency nor the length of follow-up has been established.
      Polyps that are larger than 10 mm are typically excised, although lower size
      thresholds for cholecystectomy may be considered for patients with increased risk
      for gallbladder carcinoma, such as patients with primary sclerosing cholangitis.

PMID- 25763725
TI  - Testicular tumors: what radiologists need to know--differential diagnosis,
      staging, and management.
AB  - Cryptorchidism, family history, and infertility are risk factors for testicular
      cancer. Most testicular cancers occur in young men aged 18-35 years, and seminoma
      is the most common cell type. Testicular tumors are usually diagnosed at
      ultrasonography (US) and are staged at computed tomography (CT) or magnetic
      resonance (MR) imaging. At US, testicular tumors usually appear as a solid
      intratesticular mass. Because the differential diagnosis includes infarct and
      infection, correlation with patient history and symptoms is important. At staging
      CT or MR imaging, retroperitoneal lymph nodes are considered regional lymph
      nodes, and the greatest nodal diameter is used to distinguish among N1-N3
      disease. The right testicular vein drains into the inferior vena cava, and the
      left testicular vein drains into the left renal vein. Because of venous and
      lymphatic drainage pathways, retroperitoneal lymph nodes are the initial landing
      station for testicular cancers. Enlarged lymph nodes in the supraclavicular
      region, chest, and pelvis are considered distant metastases. Testicular cancer is
      initially treated with orchiectomy. The patient may then undergo active
      surveillance, chemotherapy, radiation therapy, or retroperitoneal lymph node
      resection, depending primarily on the clinical stage. Radiologists play an
      important role in initial diagnosis, staging, and imaging surveillance of
      testicular malignancies.

PMID- 25763726
TI  - Rethinking the role of the radiologist: enhancing visibility through both
      traditional and nontraditional reporting practices.
AB  - The written radiology report is the primary method by which the radiologist
      communicates examination findings to the referring physician and the patient.
      Unfortunately, despite recent efforts to improve radiology reporting practices,
      dissatisfaction with regard to traditional reporting practices continues among
      referring physicians and patients. Moreover, the current reporting paradigm
      limits the amount of interaction that radiologists can have with patients and
      referring physicians. To address these issues, organizational efforts have been
      made by the Radiological Society of North America and the American College of
      Radiology to educate the public about the role of the radiologist in patient
      care, provide resources for individuals to learn more about the practice of
      radiology, and assist radiologists in creating a more "patient-centered"
      practice. In addition, individual radiologists may want to consider making
      adjustments to their reporting practices to improve communication of examination
      findings and increase patient awareness of the radiologist's role in clinical
      care. Many opportunities exist for radiologists to make such changes, both within
      the traditional reporting model (decreasing barriers to communication, educating
      patients) and with implementation of various nontraditional reporting practices
      (eg, delivering examination results directly to patients, receiving structured
      feedback on reports, establishing a diagnostic radiology consultation clinic).
      The authors provide guidance for radiologists who wish to enhance their
      visibility in clinical care with use of both traditional and nontraditional
      reporting practices.

PMID- 25763727
TI  - Cancer immunotherapy: imaging assessment of novel treatment response patterns and
      immune-related adverse events.
AB  - Cancer immunotherapy is changing the imaging evaluation of cancer treatment
      response and treatment-related toxic effects. New emerging patterns of treatment
      response and treatment-related toxic effects after treatment with
      immunomodulating agents have been observed. Treatment response after
      immunomodulatory therapy can be associated with significantly delayed decrease in
      tumor size, and new or enlarging tumors observed soon after completion of
      treatment may not reflect disease progression. In addition, activation of the
      immune system to fight cancer may lead to unwanted autoimmune-mediated toxic
      effects that could be mistaken for metastatic disease or misdiagnosed as a non
      treatment-related process and delay appropriate clinical management. Radiologists
      must recognize the novel treatment response patterns and the wide range of
      autoimmune toxic effects, which should not be mistaken for treatment failure or
      metastatic disease progression.

PMID- 25763728
TI  - MR imaging and PET/CT in diagnosis and management of multiple myeloma.
AB  - Multiple myeloma is a common hematologic malignancy among the elderly population.
      Although there have been many advances in treatment over the past few decades,
      the overall prognosis for the disease remains poor. Conventional radiography has
      long been the standard of reference for the imaging of multiple myeloma. However,
      10%-20% of patients with multiple myeloma do not have evidence of disease at
      conventional radiography. There is a growing body of evidence supporting use of
      magnetic resonance (MR) imaging and 2-[fluorine-18]fluoro-2-deoxy-D-glucose (FDG)
      positron emission tomography (PET)/computed tomography (CT) in diagnosis and
      management of multiple myeloma. MR imaging is useful in detection of bone marrow
      infiltration, a finding often missed at conventional radiography. FDG PET/CT is
      especially sensitive for the detection of extramedullary disease and can help
      detect the metabolically active lesions that often precede evidence of osseous
      destruction at conventional radiography. MR imaging and FDG PET/CT are useful
      tools that can provide essential information for diagnosis and management of
      patients with multiple myeloma. Both modalities allow accurate localization of
      disease after chemotherapy or autologous stem cell transplantation and can
      provide important prognostic information that can influence further clinical
      decision making regarding therapy, particularly when tumor serum markers may be a
      less reliable indicator of disease burden after repeated treatments.

PMID- 25763729
TI  - Anti-VEGF molecular targeted therapies in common solid malignancies:
      comprehensive update for radiologists.
AB  - Angiogenesis is an essential component of the growth and dissemination of solid
      malignancies and is mediated by several proangiogenic factors. The most widely
      studied proangiogenic factor is vascular endothelial growth factor (VEGF). A
      major class of molecular targeted therapies (MTTs) inhibit the VEGF axis and are
      referred to as antiangiogenic MTTs. There are two main types of anti-VEGF MTTs:
      drugs targeting circulating VEGF and drugs interfering with the activity of the
      VEGF receptors. The cancers against which antiangiogenic MTTs have had the
      greatest effect are gliomas, non-small cell lung cancer, colorectal cancer,
      hepatocellular carcinoma, renal cell carcinoma, and gastrointestinal stromal
      tumor. These cancers respond to antiangiogenic MTTs in a different way than they
      respond to conventional chemotherapy. Instead of the traditional Response
      Evaluation Criteria in Solid Tumors (RECIST), each of these cancers therefore
      requires its own individualized treatment response criteria (TRC). Examples of
      individualized TRC include the Response Assessment in Neuro-oncology (RANO)
      criteria for gliomas, modified RECIST for hepatocellular carcinoma, and
      Morphology, Attenuation, Size, and Structure (MASS) criteria for renal cell
      carcinoma. Furthermore, antiangiogenic MTTs have a unique spectrum of class
      specific and drug-specific toxic effects, some of which can be detected at
      imaging. Increasing use of antiangiogenic MTTs in clinical practice necessitates
      that radiologists be aware of these drugs, their response patterns, and TRC as
      well as their toxic effect profiles.

PMID- 25763730
TI  - Acute shoulder trauma: what the surgeon wants to know.
AB  - Many excellent studies on shoulder imaging from a radiologic perspective have
      been published over the years, demonstrating the anatomy and radiologic findings
      of shoulder trauma. However, it may not always be clear what the surgeon, who
      bears the responsibility for treating the injured patient, really needs to know
      about the injury to predict outcomes and plan management. The authors review the
      relevant osseous, soft-tissue, and vascular anatomy and describe the clinically
      relevant concepts that affect management. Familiarity with the Neer
      classification system for proximal humerus fractures can have a significant
      impact on treatment. The length and displacement of the medial humeral
      metaphyseal fragment helps predict the risk of ischemia in proximal humerus
      fractures. The Nofsinger approach for measuring the area of glenoid fossa bone
      loss can help the surgeon determine the need for surgical repair of a bony
      Bankart lesion. The size of Hill-Sachs and reverse Hill-Sachs lesions is also an
      important predictor of stability. The Ideberg classification system for
      intraarticular fractures of the glenoid fossa, combined with information on
      instability and joint incongruity, helps determine the need for surgical fixation
      of glenoid fossa fractures. Awareness of what matters to the surgeon can help
      radiologists better determine where to focus their attention and efforts when
      describing acute shoulder trauma.

PMID- 25763731
TI  - Nontuberculous mycobacterial tenosynovitis: AIRP best cases in radiologic
      pathologic correlation.

PMID- 25763732
TI  - CT angiography of the cerebral venous system: anatomic structure, pathologic
      features, and pitfalls: resident and fellow education feature.

PMID- 25763733
TI  - Somatostatin receptor imaging with 68Ga DOTATATE PET/CT: clinical utility, normal
      patterns, pearls, and pitfalls in interpretation.
AB  - Gallium 68 ((68)Ga) 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid
      (DOTA)-octreotate (DOTATATE, GaTate) positron emission tomography (PET)/computed
      tomography (CT) is an imaging technique for detecting and characterizing
      neuroendocrine tumors (NETs). GaTate, a somatostatin analog, has recently been
      accorded orphan drug status by the U.S. Food and Drug Administration, thereby
      increasing interest in and availability of this radiotracer. GaTate PET/CT allows
      whole-body imaging of cell surface expression of somatostatin receptors (SSTRs)
      and is rapidly evolving as the new imaging standard of reference for the
      detection and characterization of NETs. The authors discuss the normal appearance
      at GaTate PET/CT and the utility of this modality in a variety of these tumors,
      including gastrointestinal, pancreatic, and bronchial NETs as well as
      pheochromocytoma, paraganglioma, meningioma, and oncogenic osteomalacia. In
      addition, they discuss potential causes of false-positive findings, including
      pancreatic uncinate process activity, inflammation, osteoblastic activity, and
      splenosis. They also highlight the complementary role of 2-[fluorine-18]fluoro-2
      deoxy-d-glucose (FDG) PET/CT, including the advantages of using both GaTate
      PET/CT and FDG PET/CT to evaluate sites of well- and poorly differentiated
      disease. The use of GaTate PET/CT together with FDG PET/CT allows identification
      of tumor heterogeneity, which provides prognostic information and can be pivotal
      in guiding biopsy. It also allows optimal patient management, including
      theranostic application of peptide receptor radionuclide therapy, and the
      restaging of patients following therapy.

PMID- 25763734
TI  - Invited commentary.

PMID- 25763735
TI  - Invited commentary.

PMID- 25763736
TI  - Intraperitoneal solid tumors in children.

PMID- 25763737
TI  - Solid tumors of the peritoneum, omentum, and mesentery in children: radiologic
      pathologic correlation: from the radiologic pathology archives.
AB  - Intraperitoneal solid tumors are far less common in children than in adults, and
      the histologic spectrum of neoplasms of the peritoneum and its specialized folds
      in young patients differs from that in older patients. Localized masses may be
      caused by inflammatory myofibroblastic tumor, Castleman disease, mesenteric
      fibromatosis, or other mesenchymal masses. Inflammatory myofibroblastic tumor is
      a mesenchymal tumor of borderline biologic potential that appears as a solitary
      circumscribed mass, possibly with central calcification. Castleman disease is an
      idiopathic lymphoproliferative disorder that appears as a circumscribed,
      intensely enhancing mass in the mesentery. Mesenteric fibromatosis, or intra
      abdominal desmoid tumor, is a benign tumor of mesenchymal origin associated with
      familial adenomatous polyposis. Mesenteric fibromatosis appears as a mildly
      enhancing, circumscribed solitary mass without metastases. Diffuse peritoneal
      disease may be due to desmoplastic small round cell tumor (DSRCT), non-Hodgkin
      lymphoma, or rhabdomyosarcoma. DSRCT is a rare member of the small round blue
      cell tumor family that causes diffuse peritoneal masses without a visible primary
      tumor. A dominant mass is typically found in the retrovesical space. Burkitt
      lymphoma is a pediatric tumor that manifests with extensive disease because of
      its short doubling time. The bowel and adjacent mesentery are commonly involved.
      Rhabdomyosarcoma may arise as a primary tumor of the omentum or may spread from a
      primary tumor in the bladder, prostate, or scrotum. Knowledge of this spectrum of
      disease allows the radiologist to provide an appropriate differential diagnosis
      and suggest proper patient management. 

PMID- 25763738
TI  - The malpractice liability of radiology reports: minimizing the risk.
AB  - The art and science of interpreting radiologic examinations, an ability that is
      acquired over years of training, is on display in every radiology report. It is
      vital that these reports be crafted so as to both reflect the radiologist's
      expertise and capability and eliminate any factors that might result in
      unintended harm to the patient. Unfortunately, a deficient report may result in
      legal action against the radiologist; thus, a thorough understanding of the
      litigious potential of the language used in radiology reports is crucial. It is
      important that ambiguous vocabulary, undefined modifiers, double negatives, and
      generalizations be avoided. Errors in radiology reports may result from
      inappropriate terminology, transcription mistakes, or deficient or inadequately
      documented communication. Critical findings that may have an immediate impact on
      patient management must be promptly communicated to the referring physician and
      such communication fully documented. A meticulous and well-written report is the
      best way for radiologists to care for their patients. In addition, a well-worded
      report can be the deciding factor in a successful defense against a malpractice
      claim. Understanding the legal implications of radiology reports will enable
      radiologists to develop strategies for avoiding malpractice suits.

PMID- 25763739
TI  - Acetabular fractures: what radiologists should know and how 3D CT can aid
      classification.
AB  - Correct recognition, description, and classification of acetabular fractures is
      essential for efficient patient triage and treatment. Acetabular fractures may
      result from high-energy trauma or low-energy trauma in the elderly. The most
      widely used acetabular fracture classification system among radiologists and
      orthopedic surgeons is the system of Judet and Letournel, which includes five
      elementary (or elemental) and five associated fractures. The elementary fractures
      are anterior wall, posterior wall, anterior column, posterior column, and
      transverse. The associated fractures are all combinations or partial combinations
      of the elementary fractures and include transverse with posterior wall, T-shaped,
      associated both column, anterior column or wall with posterior hemitransverse,
      and posterior column with posterior wall. The most unique fracture is the
      associated both column fracture, which completely dissociates the acetabular
      articular surface from the sciatic buttress. Accurate categorization of
      acetabular fractures is challenging because of the complex three-dimensional (3D)
      anatomy of the pelvis, the rarity of certain acetabular fracture variants, and
      confusing nomenclature. Comparing a 3D image of the fractured acetabulum with a
      standard diagram containing the 10 Judet and Letournel categories of acetabular
      fracture and using a flowchart algorithm are effective ways of arriving at the
      correct fracture classification. Online supplemental material is available for
      this article.

PMID- 25763740
TI  - Imaging evaluation of the inferior vena cava.
AB  - The inferior vena cava (IVC) is an essential but often overlooked structure at
      abdominal imaging. It is associated with a wide variety of congenital and
      pathologic processes and can be a source of vital information for referring
      clinicians. Initial evaluation of the IVC is most likely to occur at computed
      tomography performed for another indication. Many routine abdominal imaging
      protocols may result in suboptimal evaluation of the IVC; however, techniques to
      assist in specific evaluation of the IVC can be used. In this article, the
      authors review the spectrum of IVC variants and pathologic processes and the
      relevant findings from magnetic resonance imaging, angiography, sonography, and
      positron emission tomography. Embryologic development of the IVC and examples of
      congenital IVC variants, such as absence, duplication, left-sided location,
      azygous or hemiazygous continuation, and web formation, are described. The
      authors detail IVC involvement in Wilms tumor, leiomyosarcoma, adrenal cortical
      carcinoma, testicular carcinoma, hepatocellular carcinoma, renal cell carcinoma,
      and other neoplasms, as well as postsurgical, traumatic, and infectious entities
      (including filter malposition, mesocaval shunt, and septic thrombophlebitis). The
      implications of these entities for patient treatment and instances in which
      specific details should be included in the dictated radiology report are
      highlighted. Furthermore, the common pitfalls of IVC imaging are discussed. The
      information provided in this review will allow radiologists to detect and
      accurately characterize IVC abnormalities to guide clinical decision making and
      improve patient care.

PMID- 25763741
TI  - Endovascular repair of abdominal aortic aneurysms: vascular anatomy, device
      selection, procedure, and procedure-specific complications.
AB  - Abdominal aortic aneurysm (AAA) is abnormal dilatation of the aorta, carrying a
      substantial risk of rupture and thereby marked risk of death. Open repair of AAA
      involves lengthy surgery time, anesthesia, and substantial recovery time.
      Endovascular aneurysm repair (EVAR) provides a safer option for patients with
      advanced age and pulmonary, cardiac, and renal dysfunction. Successful
      endovascular repair of AAA depends on correct selection of patients (on the basis
      of their vascular anatomy), choice of the correct endoprosthesis, and familiarity
      with the technique and procedure-specific complications. The type of aneurysm is
      defined by its location with respect to the renal arteries, whether it is a true
      or false aneurysm, and whether the common iliac arteries are involved. Vascular
      anatomy can be divided more technically into aortic neck, aortic aneurysm, pelvic
      perfusion, and iliac morphology, with grades of difficulty with respect to EVAR,
      aortic neck morphology being the most common factor to affect EVAR
      appropriateness. When choosing among the devices available on the market, one
      must consider the patient's vascular anatomy and choose between devices that
      provide suprarenal fixation versus those that provide infrarenal fixation. A
      successful technique can be divided into preprocedural imaging, ancillary
      procedures before AAA stent-graft placement, the procedure itself, postprocedural
      medical therapy, and postprocedural imaging surveillance. Imaging surveillance is
      important in assessing complications such as limb thrombosis, endoleaks, graft
      migration, enlargement of the aneurysm sac, and rupture. Last, one must consider
      the issue of radiation safety with regard to EVAR.

PMID- 25763742
TI  - Leiomyosarcoma of the inferior vena cava: AIRP best cases in radiologic
      pathologic correlation.

PMID- 25763743
TI  - Fetal ovarian cysts: review of imaging spectrum, differential diagnosis,
      management, and outcome.
AB  - Fetal ovarian cysts are the most common abdominal cysts observed in the female
      fetus but may be mistaken for genitourinary cysts, gastrointestinal cysts,
      lymphangiomas, or fetus in fetu. Ultrasonography (US) is the imaging modality of
      choice for fetal assessment, and magnetic resonance imaging is a useful problem
      solving tool when uncertainty remains after careful US evaluation. At US, a fetal
      ovarian cyst manifests as an anechoic thin-walled cyst superior and parasagittal
      to the bladder. A daughter cyst may occasionally be observed and is pathognomonic
      for a cyst of ovarian origin. Fetal ovarian cysts may be simple or complicated
      and unilateral or bilateral, and they may masquerade as a solid mass when
      hemorrhage or torsion occurs. Complicated cysts may exhibit multiple septations,
      fluid-fluid levels, or mobile internal echoes. It is important to differentiate a
      hemorrhagic ovarian cyst from solid abdominal neoplasms that may be seen in a
      fetus. Recognition of the pertinent imaging findings will help radiologists
      distinguish fetal ovarian cysts from other fetal intra-abdominal masses in the
      differential diagnosis. Malignant ovarian neoplasms are rare in the fetus and
      neonate and thus are not considered in the differential diagnosis. The current
      literature on the management and outcome of fetal ovarian cysts is reviewed, with
      imaging studies presented from the authors' practice. Most fetal ovarian cysts
      resolve spontaneously; if operative intervention is required, the goal should be
      ovarian preservation.

PMID- 25763744
TI  - Complex abdominal wall defects: appearances at prenatal imaging.
AB  - Abdominal wall defects are a complex group of anomalies, and many are incorrectly
      diagnosed. Evaluation of the defect relative to the umbilical cord insertion site
      is fundamentally important in differentiating among the various malformations.
      The two most common abdominal wall defects are gastroschisis, in which the defect
      is on the right side of the normally inserting cord and free-floating bowel loops
      are present, and omphalocele, in which the cord inserts on a membrane-covered
      midline defect. Omphalocele may also form a portion of a more complex defect that
      may remain undiagnosed without thorough evaluation. In cloacal exstrophy, the
      defect extends inferiorly and the bowel loops extrude between the two bladder
      halves. In pentalogy of Cantrell, the defect extends superiorly and is typically
      associated with ectopia cordis. Bladder exstrophy is a lower abdominal defect in
      which the hallmark finding is absence of a fluid-filled bladder. The cord
      insertion site is normal to low but does not form part of the defect. Both body
      stalk anomaly and abdominoschisis due to amniotic bands cause severe
      malformations, often involving extrusion of solid organs and the bowel. Although
      these two entities have many overlapping features, body stalk anomaly may be
      recognized on the basis of absence of a free-floating umbilical cord. With use of
      an algorithmic approach beginning with discovery of the location of the defect, a
      more precise diagnosis can be determined that may directly affect pre- and
      postnatal management decisions.

PMID- 25763745
TI  - IT challenges for the aging radiologist: practice corner.

PMID- 25763746
TI  - High-resolution US and MR imaging of peroneal tendon injuries--erratum.

PMID- 25763747
TI  - CT colonography with computer-aided detection: recognizing the causes of false
      positive reader results--erratum.

PMID- 25763748
TI  - Gone but not completely forgotten: pictorial review of "antiquated" radiologic
      procedures--erratum.

PMID- 25763749
TI  - Notice of redundant publication.

PMID- 25763750
TI  - William J. Tuddenham, MD 1923-2014.

PMID- 25763751
TI  - Discoveries and advances in plant and animal genomics.
AB  - Plant and animal genomics is a broad area of research with respect to the
      biological issues covered because it continues to deal with the structure and
      function of genetic material underpinning all organisms. This mini-review
      utilizes the plenary lectures from the Plant and Animal Genome Conference as a
      basis for summarizing the trends in the genome-level studies of organisms. 

PMID- 25763752
TI  - Two distinct classes of protein related to GTB and RRM are critical in the
      sclerotial metamorphosis process of Rhizoctonia solani AG-1 IA.
AB  - Sheath blight of rice, caused by Rhizoctonia solani Kuhn AG-1 IA [teleomorph:
      Thanatephorus cucumeris (Frank) Donk], is one of the major diseases of rice
      (Oryza sativa L.) worldwide. Sclerotia produced by R. solani AG-1 IA are crucial
      for their survival in adverse environments and further dissemination when
      environmental conditions become conducive. Differentially expressed genes during
      three stages of sclerotial metamorphosis of R. solani AG-1 IA were investigated
      by utilizing complementary DNA amplified fragment length polymorphism (cDNA-AFLP)
      technique. A total of 258 transcript derived fragments (TDFs) were obtained and
      sequenced, among which 253 TDFs were annotated with known functions through
      BLASTX by searching the GenBank database and 19 annotated TDFs were assigned into
      19 secondary metabolic pathways through searching the Kyoto Encyclopedia of Genes
      and Genomes (KEGG) PATHWAY database. Moreover, the results of quantitative real
      time PCR (qRT-PCR) analysis showed that the expression patterns of eight
      representative annotated TDFs were positively correlated with sclerotial
      metamorphosis. Sequence annotation of TDFs showed homology similarities to
      several genes encoding for proteins belonging to the glycosyltransferases B (GTB)
      and RNA recognition motif (RRM) superfamily and to other development-related
      proteins. Taken together, it is concluded that the members of the GTB and RRM
      superfamilies and several new genes involved in proteolytic process identified in
      this study might serve as the scavengers of free radicals and reactive oxygen
      species (ROS) and thus play an important role in the sclerotial metamorphosis
      process of R. solani AG-1 IA. 

PMID- 25763753
TI  - Bisphosphonate therapy in metastatic carcinoma patients with chronic renal
      failure: are bisphosphonates an enemy or crony?

PMID- 25763754
TI  - Clinical implications of malnutrition in children with cancer.

PMID- 25763755
TI  - Development and first data of a customized short tracheal cannula based on
      digital data.
AB  - PURPOSE: At the moment, there is an inadequate margin fit of commercially
      available stoma buttons. The aim of the present study was to develop a customized
      short tracheal cannula based on digital data. Furthermore, the applied material
      has to be evaluated considering germ colonization and appropriate cleaning
      procedures. METHODS: Computed tomographies of 53 patients who underwent
      laryngectomy were surveyed. Based on the digital data, a customized short
      tracheal cannula was created and manufactured from silicone. The new cannula was
      incorporated in ten patients and worn for 4 weeks. A clinical examination of an
      otolaryngologist and subjective assessment of the patients were carried out.
      Furthermore, microbiological test considering germ colonization was performed.
      RESULTS: The customized short tracheal cannula could be incorporated in all
      patients. The clinical results showed no irritation or mucosal lesions. The
      subjective individual evaluation by the patients was promising. The proposals for
      improvement could be considered. The microbiological examination revealed a
      higher contamination of the silicone compared to the silver cannulas. Both
      chemical and mechanical decontamination showed sufficient results. CONCLUSION: A
      workflow for development and manufacturing of a customized short tracheal cannula
      from digital data could be established. The cannula is compatible to standard
      equipment and routine cleaning procedures. Clinical studies are required to
      evaluate the potential benefit for patients.

PMID- 25763756
TI  - Acute brain failure in severe sepsis: a prospective study in the medical
      intensive care unit utilizing continuous EEG monitoring.
AB  - PURPOSE: Investigate the prevalence, risk factors and impact of continuous EEG
      (cEEG) abnormalities on mortality through the 1-year follow-up period in patients
      with severe sepsis. METHODS: Prospective, single-center, observational study of
      consecutive patients admitted with severe sepsis to the Medical ICU at an
      academic medical center. RESULTS: A total of 98 patients with 100 episodes of
      severe sepsis were included; 49 patients (50%) were female, median age was 60
      (IQR 52-74), the median non-neuro APACHE II score was 23.5 (IQR 18-28) and median
      non-neuro SOFA score was 8 (IQR 6-11). Twenty-five episodes had periodic
      discharges (PD), of which 11 had nonconvulsive seizures (NCS). No patient had NCS
      without PD. Prior neurological history was associated with a higher risk of PD or
      NCS (45 vs. 17%; CI 1.53-10.43), while the non-neuro APACHE II, non-neuro SOFA,
      severity of cardiovascular shock and presence of sedation during cEEG were
      associated with a lower risk of PD or NCS. Clinical seizures before cEEG were
      associated with a higher risk of nonconvulsive status epilepticus (24 vs. 6%; CI
      1.42-19.94) while the non-neuro APACHE II and non-neuro SOFA scores were
      associated with a lower risk. Lack of EEG reactivity was present in 28% of
      episodes. In the survival analysis, a lack of EEG reactivity was associated with
      higher 1-year mortality [mean survival time 3.3 (95% CI 1.8-4.9) vs. 7.5 (6.4
      8.7) months; p = 0.002] but the presence of PD or NCS was not [mean survival time
      3.3 (95% CI 1.8-4.9) vs. 7.5 (6.4-8.7) months; p = 0.592]. Lack of reactivity was
      more frequent in patients on continuous sedation during cEEG. In patients with
      available 1-year data (34% of the episodes), 82% had good functional outcome (mRS
      <= 3, n = 27). There were no significant predictors of functional outcome, late
      cognition, and no patient with complete follow-up data developed late seizure or
      new epilepsy. CONCLUSIONS: NCS and PD are common in patients with severe sepsis
      and altered mental status. They were less frequent among the most severely sick
      patients and were not associated with outcome in this study. Lack of EEG
      reactivity was more frequent in patients on continuous sedation and was
      associated with mortality up to 1 year after discharge. Larger studies are needed
      to confirm these findings in a broader population and to further evaluate long
      term cognitive outcome, risk of late seizure and epilepsy.

PMID- 25763757
TI  - Salivary Microbiota Associated with Immunoglobulin A Nephropathy.
AB  - This study aimed at investigating the salivary microbiota of 28 patients affected
      by immunoglobulin A nephropathy (IgAN). Fourteen healthy volunteers (HC) were
      used as control. Compared to HC, the number of some cultivable bacteria groups
      (e.g., total anaerobes) significantly (P < 0.05) decreased in the salivary
      samples of IgAN patients. Total bacteria from salivary samples of IgAN patients
      and HC subjects were analyzed by pyrosequencing of 16S rRNA gene. Paired t test
      showed no significant (P > 0.05) differences of alpha-diversity parameters (OTU,
      ACE, Chao1, and Shannon index) between the salivary samples of HC and IgAN
      patients. The difference for the community structure was further analyzed using
      three phylogeny-based beta-diversity measures. Compared to HC, the ratio between
      Firmicutes/Proteobacteria markedly decreased in IgAN patients. Gemella
      haemolysins, Granulicatella adiacens, and Veillonella parvula were positively
      associated (P < 0.05) with HC. Within the phylum Bacteroidetes, Prevotella
      species (Prevotella nigrescens, Prevotella intermedia, Prevotella pallens, and
      Prevotella salivae) were the highest in HC. The only exception was for Prevotella
      aurantiaca. Compared to HC, the percentage of abundance of some species,
      belonging to Pasteurellaceae family (e.g., Haemophylus parainfluenzae), increased
      in IgAN patients. Fusobacteriaceae (Fusobacterium) and Corynebacterium sp. also
      differed between the salivary samples of HC and IgAN patients. 

PMID- 25763758
TI  - Development of regional stroke programs.
AB  - The organization of stroke care has undergone a dramatic evolution in the USA
      over the last two decades. Beginning with the recommendation for Primary Stroke
      Centers (PSCs) in 1994, there has been a concerted effort by physicians, the
      American Heart Association/American Stroke Association (AHA/ASA), National
      Institutes of Health (NIH), and state legislatures to advance an evidence-based
      system of care with several tiers of stroke centers. At the apex of this
      structure are Regional Stroke Centers (RSCs), which do not have official
      recognition like PSCs and Comprehensive Stroke Centers (CSCs), but their
      existence as a hub for the many disparate spokes of stroke care in their region
      is increasingly necessary. Observational evidence suggests that this approach is
      improving the delivery of stroke care and reducing costs in the USA. Similar
      efforts are being made in Europe and Asia with encouraging results. The RSC model
      has the potential to lead to more uniform evidence-based stroke medicine, but
      many challenges exist. 

PMID- 25763759
TI  - Locked Deflection During Flexible Ureteroscopy: Incidence and Elucidation of the
      Mechanism of an Underreported Complication.
AB  - BACKGROUND AND PURPOSE: Flexible ureteroscopy (URS) is widely implemented with a
      well-defined safety profile and low complication rates. Although rare, locked
      deflection of a flexible ureteroscope in the upper tract is a potentially serious
      complication with poorly understood etiology and is likely underreported.
      MATERIALS AND METHODS: We attempted to capture all cases of locked deflection
      during URS by performing an anonymous, online computer survey targeting members
      of the Endourological Society. The Manufacturer and User Facility Device
      Experience (MAUDE) database and published literature were queried to find
      additional cases. The indication for URS, method of ureteroscope removal, patient
      outcomes, incident reporting, and explanations provided by the manufacturer or
      third party repair service were obtained whenever possible. RESULTS: In total, 10
      cases of locked deflection during flexible URS were identified. Survey responses
      were obtained from 250/2424 (10.3%) endourologists polled. Locked deflection was
      noted by 8/250 (3.2%). The reported literature and MAUDE database identified one
      case each. Successful removal was noted in four using retrograde manipulation
      techniques while a percutaneous approach was used in three patients. Open surgery
      was needed in two cases because of resultant ureteral avulsion, and in one case,
      an open ureterotomy was needed for ureteroscope extraction. According to our
      survey, locked deflection was reported to the patient in 4/8 cases, the hospital
      in 3/8 cases, and the Food and Drug Administration (FDA) 0/8 cases. The two cases
      reported outside of our survey both notified the FDA. The minority of respondents
      (2/8), including our group, felt improper surgical technique was responsible for
      resultant locked deflection. Specifically, removal of a completely deflected
      ureteroscope through a stenotic infundibulum should be avoided. Rather, in such a
      situation, the ureteroscope should be straightened under fluoroscopy before being
      withdrawn. CONCLUSIONS: Locked deflection of a flexible ureteroscope is rare and
      underreported. Some cases are attributed to surgical technique, and awareness is
      crucial for avoidance of this complication.

PMID- 25763760
TI  - Essay: a lesson in living.
AB  - This 2013 Consortium of Universities for Global Health essay examines the ethical
      dilemmas encountered by a public health worker engaged in HIV/AIDS prevention and
      health promotion in a rural Tanzanian community. Is the professional objective of
      improving the health and well-being of the population so simple? 

PMID- 25763761
TI  - Optimal control of ICU patient discharge: from theory to implementation.
AB  - This paper deals with the management of scarce health care resources. We consider
      a control problem in which the objective is to minimize the rate of patient
      rejection due to service saturation. The scope of decisions is limited, in terms
      both of the amount of resources to be used, which are supposed to be fixed, and
      of the patient arrival pattern, which is assumed to be uncontrollable. This means
      that the only potential areas of control are speed or completeness of service. By
      means of queuing theory and optimization techniques, we provide a theoretical
      solution expressed in terms of service rates. In order to make this theoretical
      analysis useful for the effective control of the healthcare system, however,
      further steps in the analysis of the solution are required: physicians need
      flexible and medically-meaningful operative rules for shortening patient length
      of service to the degree needed to give the service rates dictated by the
      theoretical analysis. The main contribution of this paper is to discuss how the
      theoretical solutions can be transformed into effective management rules to guide
      doctors' decisions. The study examines three types of rules based on intuitive
      interpretations of the theoretical solution. Rules are evaluated through
      implementation in a simulation model. We compare the service rates provided by
      the different policies with those dictated by the theoretical solution.
      Probabilistic analysis is also included to support rule validity. An Intensive
      Care Unit is used to illustrate this control problem. The study focuses on the
      Markovian case before moving on to consider more realistic LoS distributions
      (Weibull, Lognormal and Phase-type distribution). 

PMID- 25763762
TI  - Potential relationship between single nucleotide polymorphisms used in forensic
      genetics and diseases or other traits in European population.
AB  - Single nucleotide polymorphisms (SNPs) are an interesting option to facilitate
      the analysis of highly degraded DNA by allowing the reduction of the size of the
      DNA amplicons. The SNPforID 52-plex panel is a clear example of the use of non
      coding SNPs in forensic genetics. However, nonstop advances in studies of genetic
      polymorphisms are leading to the discovery of new associations between SNPs and
      diseases. The aim of this study was to perform a comprehensive review of the
      state of association between the 52 SNPs in the 52-plex panel and diseases or
      other traits related to their treatment, such as drug response characters. In
      order to achieve this goal, we have conducted a bioinformatic search for each SNP
      included in the panel and the SNPs in linkage disequilibrium (LD) with them in
      the European population (r (2)  > 0.8). A total of 424 SNPs (52 in the panel and
      372 in LD) were investigated in PubMed, Scopus, and dbSNP databases. Our results
      show that three SNPs in the SNPforID 52-plex panel (rs2107612, rs1979255,
      rs1463729) have been associated with diseases such as hypertension or macular
      degeneration, as well as drug response. Similarly, three out of the 372 SNPs in
      LD (rs2107614, r (2)  = 0.859; rs765250, r (2)  = 0.858; rs11064560, r (2)  =
      0,887) are also associated with various pathologies. In view of these results, we
      propose the need for a periodic review of the SNPs used in forensic genetics in
      order to keep their associations with diseases or related phenotypes updated and
      to evaluate their continuity in forensic panels for avoiding legal and ethical
      conflicts. 

PMID- 25763765
TI  - Applying metabolomic analyses to the practice of embryology: physiology,
      development and assisted reproductive technology.
AB  - The advent of metabolomics technology and its application to small samples has
      allowed us to non-invasively monitor the metabolic activity of embryos in a
      complex culture environment. The aim of this study was to apply metabolomics
      technology to the analysis of individual embryos from several species during in
      vitro development to gain an insight into the metabolomics pathways used by
      embryos and their relationship with embryo quality. Alanine is produced by both
      in vivo- and in vitro-derived human, murine, bovine and porcine embryos.
      Glutamine is also produced by the embryos of these four species, but only those
      produced in vitro. Across species, blastocysts significantly consumed amino acids
      from the culture medium, whereas glucose was not significantly taken up. There
      are significant differences in the metabolic profile of in vivo- compared with in
      vitro-produced embryos at the blastocyst stage. For example, in vitro-produced
      murine embryos consume arginine, asparagine, glutamate and proline, whereas in
      vivo-produced embryos do not. Human embryos produce more alanine, glutamate and
      glutamine, and consume less pyruvate, at the blastocyst compared with cleavage
      stages. Glucose was consumed by human blastocysts, but not at a high enough level
      to reach significance. Consumption of tyrosine by cleavage stage human embryos is
      indicative of blastocyst development, although tyrosine consumption is not
      predictive of blastocyst quality. Similarly, although in vivo-produced murine
      blastocysts consumed less aspartate, lactate, taurine and tyrosine than those
      produced in vitro, consumption of these four amino acids by in vitro-derived
      embryos with high octamer-binding transcription factor 4 (Oct4) expression,
      indicative of high quality, did not differ from those with low Oct4 expression.
      Further application of metabolomic technologies to studies of the consumption
      and/or production of metabolites from individual embryos in a complete culture
      medium could transform our understanding of embryo physiology and improve our
      ability to produce developmentally competent embryos in vitro. 

PMID- 25763766
TI  - The effect of cyanobacterial biomass enrichment by centrifugation and GF/C
      filtration on subsequent microcystin measurement.
AB  - Microcystins are cyclic peptides produced by multiple cyanobacterial genera.
      After accumulation in the liver of animals they inhibit eukaryotic
      serine/threonine protein phosphatases, causing liver disease or death. Accurate
      detection/quantification of microcystins is essential to ensure safe water
      resources and to enable research on this toxin. Previous methodological
      comparisons have focused on detection and extraction techniques, but have not
      investigated the commonly used biomass enrichment steps. These enrichment steps
      could modulate toxin production as recent studies have demonstrated that high
      cyanobacterial cell densities cause increased microcystin levels. In this study,
      three microcystin-producing strains were processed using no cell enrichment steps
      (by direct freezing at three temperatures) and with biomass enrichment (by
      centrifugation or GF/C filtration). After extraction, microcystins were analyzed
      using liquid chromatography-tandem mass spectrometry. All processing methods
      tested, except GF/C filtration, resulted in comparable microcystin quotas for all
      strains. The low yields observed for the filtration samples were caused by
      adsorption of arginine-containing microcystins to the GF/C filters. Whilst
      biomass enrichment did not affect microcystin metabolism over the time-frame of
      normal sample processing, problems associated with GF/C filtration were
      identified. The most widely applicable processing method was direct freezing of
      samples as it could be utilized in both field and laboratory environments. 

PMID- 25763767
TI  - Insights into the Interaction Mechanism of Ligands with Abeta42 Based on
      Molecular Dynamics Simulations and Mechanics: Implications of Role of Common
      Binding Site in Drug Design for Alzheimer's Disease.
AB  - Aggregation of beta-amyloid (Abeta) into oligomers and further into fibrils is
      hypothesized to be a key factor in pathology of Alzheimer's disease (AD). In this
      study, mapping and docking were used to study the binding of ligands to
      protofibrils. It was followed by molecular simulations to understand the
      differences in interactions of known therapeutic agents such as curcumin,
      fluorescence-based amyloid staining agents such as thioflavin T, and diagnostic
      agents such as florbetapir (AV45), with Abeta protofibrils. We show that
      therapeutic agents bind to and distort the protofibrils, thus causing
      destabilization or prevention of oligomerization, in contrast to diagnostic
      agents which bind to but do not distort such structures. This has implications in
      the rational design of ligands, both for diagnostics and therapeutics of AD. 

PMID- 25763768
TI  - An updated survey for the 2007-2013 period of randomized controlled trials for
      psoriasis: treatment modalities, study designs, comparators, outcome measures and
      sponsorship.
AB  - BACKGROUND: Two reports from the European Dermato-Epidemiology Network psoriasis
      project have analysed randomized controlled trials for psoriasis published during
      the periods of 1977-2000 and 2001-2006. OBJECTIVE: We sought to update the
      analysis of randomized controlled trials for the 2007-2013 period from 10 high
      impact dermatology and medical journals. METHODS: This survey was conducted by
      electronic search on the PubMed database for eligible papers. We assessed and
      compared results to the two aforementioned published reports. RESULTS: In total,
      84 studies were evaluated. Over half of the total trials studied novel
      therapeutics: 40 (47.6%) trials examined biologics and five (6.0%) examined novel
      oral agents. Proportion of trials studying more than one treatment modality
      increased from 7.1% in 2001-2006 to 25.0% in 2007-2013, with a decreased
      proportion of placebo-controlled studies from 69.3% to 47.1%. CONCLUSION: The
      proportion of trials on novel therapies, including novel oral and biologic
      agents, has increased. The quality of trials has improved in the aspects of
      increased active treatment comparisons, including between biologics and
      conventional agents, and increased study size. Further insight into the influence
      of pharmaceutical companies can be studied by extending analysis to extension
      studies and subanalyses.

PMID- 25763769
TI  - Pyoderma gangrenosum mimicking an infected foot.

PMID- 25763770
TI  - Separation of isorhamnetin 3-sulphate and astragalin from Flaveria bidentis (L.)
      Kuntze using macroporous resin and followed by high-speed countercurrent
      chromatography.
AB  - D4020 resin offered the best dynamic adsorption and desorption capacity for total
      flavonoids based on the research results from ten kinds of macroporous resin. A
      column packed with D4020 resin was used to optimize the separation of total
      flavonoids from Flaveria bidentis (L.) Kuntze extracts. The content of flavonoids
      in the product was increased from 4.3 to 30.1% with a recovery yield of 90%.
      After the treatment with gradient elution on D4020 resin, the contents of
      isorhamnetin 3-sulfate and astragalin were increased from 0.49 to 8.70% with a
      recovery yield of 74.1% and 1.16 to 30.8%, with a recovery yield of 92.2%,
      respectively. Further purification was carried out by one-run high-speed
      countercurrent chromatography yielding 4.5 mg of isorhamnetin 3-sulfate at a high
      purity of 96.48% and yielding 24.4 mg of astragalin at a high purity of over
      98.46%. 

PMID- 25763771
TI  - Ligation of TLR7 on CD19(+) CD1d(hi) B cells suppresses allergic lung
      inflammation via regulatory T cells.
AB  - B cells have been described as having the capacity to regulate cellular immune
      responses and suppress inflammatory processes. One such regulatory B-cell
      population is defined as IL-10-producing CD19(+) CD1d(hi) cells. Previous work
      has identified an expansion of these cells in mice infected with the helminth,
      Schistosoma mansoni. Here, microarray analysis of CD19(+) CD1d(hi) B cells from
      mice infected with S. mansoni demonstrated significantly increased Tlr7
      expression, while CD19(+) CD1d(hi) B cells from uninfected mice also demonstrated
      elevated Tlr7 expression. Using IL-10 reporter, Il10(-/-) and Tlr7(-/-) mice, we
      formally demonstrate that TLR7 ligation of CD19(+) CD1d(hi) B cells increases
      their capacity to produce IL-10. In a mouse model of allergic lung inflammation,
      the adoptive transfer of TLR7-elicited CD19(+) CD1d(hi) B cells reduced airway
      inflammation and associated airway hyperresponsiveness. Using DEREG mice to
      deplete FoxP3(+) T regulatory cells in allergen-sensitized mice, we show that
      that TLR7-elicited CD19(+) CD1d(hi) B cells suppress airway hyperresponsiveness
      via a T regulatory cell dependent mechanism. These studies identify that TLR7
      stimulation leads to the expansion of IL-10-producing CD19(+) CD1d(hi) B cells,
      which can suppress allergic lung inflammation via T regulatory cells. 

PMID- 25763772
TI  - DCTN4 as a modifier of chronic Pseudomonas aeruginosa infection in cystic
      fibrosis.
AB  - BACKGROUND AND AIMS: Pseudomonas aeruginosa (Pa) infection in cystic fibrosis
      (CF) patients is associated with worse long-term pulmonary disease and shorter
      survival, and chronic Pa infection (CPA) is associated with reduced lung
      function, faster rate of lung decline, increased rates of exacerbations and
      shorter survival. By using exome sequencing and extreme phenotype design, it was
      recently shown that isoforms of dynactin 4 (DCTN4) may influence Pa infection in
      CF, leading to worse respiratory disease. The purpose of this study was to
      investigate the role of DCTN4 missense variants on Pa infection incidence, age at
      first Pa infection and chronic Pa infection incidence in a cohort of adult CF
      patients from a single centre. METHODS: Polymerase chain reaction and direct
      sequencing were used to screen DNA samples for DCTN4 variants. RESULTS: A total
      of 121 adult CF patients from the Cochin Hospital CF centre have been included,
      all of them carrying two CFTR defects: 103 developed at least 1 pulmonary
      infection with Pa, and 68 patients of them had CPA. DCTN4 variants were
      identified in 24% (29/121) CF patients with Pa infection and in only 17% (3/18)
      CF patients with no Pa infection. Of the patients with CPA, 29% (20/68) had DCTN4
      missense variants vs 23% (8/35) in patients without CPA. Interestingly,
      p.Tyr263Cys tend to be more frequently observed in CF patients with CPA than in
      patients without CPA (4/68 vs 0/35), and DCTN4 missense variants tend to be more
      frequent in male CF patients with CPA bearing two class II mutations than in male
      CF patients without CPA bearing two class II mutations (P = 0.06). CONCLUSIONS:
      Our observations reinforce that DCTN4 missense variants, especially p.Tyr263Cys,
      may be involved in the pathogenesis of CPA in male CF.

PMID- 25763773
TI  - Measuring maternal health literacy in adolescents attending antenatal care in a
      developing country - the impact of selected demographic characteristics.
AB  - AIMS AND OBJECTIVES: The aim of this paper is to describe how selected
      demographic characteristics 'explain' the observed variance in the distribution
      of maternal health literacy estimates in adolescents attending antenatal care in
      Uganda, as estimated by the 'Maternal health literacy scale'. BACKGROUND: By the
      age of 20 years, more than 60% of Ugandan females are mothers. In the Busoga
      region of Uganda, the percentage of pregnant adolescents and adolescent mothers
      is at its highest (above 30%). DESIGN: Validated questionnaire survey. METHODS:
      The Maternal health literacy scale was administered to 384 adolescents aged 15-19
      years attending antenatal care in Jinja and Iganga districts of the Busoga region
      during the period of July 2013-December 2013. The Mann-Whitney U test in SPSS21
      was used to determine if the two levels of dichotomised person factors, i.e.
      demographic characteristics, relate to 'significantly' different mean maternal
      health literacy estimates, not strictly following the normal distribution, as
      measured by the Maternal health literacy scale. RESULTS: The person factors, age,
      education level, pregnancy order and prepregnancy awareness about conception,
      explained approximately 12% of the observed variance in maternal health literacy
      estimates. CONCLUSIONS: Prepregnancy awareness about conception was the single
      most contributory factor to the observed variance in estimated maternal health
      literacy levels. More research on women of childbearing age is warranted to
      explore the impact of further person factors on the maternal health literacy in
      pregnant adolescents. RELEVANCE TO CLINICAL PRACTICE: Using the person factors
      found to show 'significant' impact on maternal health literacy in pregnant
      adolescents, target-specific interventions aimed at improving maternal health
      literacy in pregnant adolescents can be formulated. By accounting for these
      factors in reproductive health policy designs, one might take preventive actions
      to curb the prevalence of adolescent pregnancies in both developing and developed
      countries.

PMID- 25763774
TI  - A genetic diagnosis of maturity-onset diabetes of the young (MODY): experiences
      of patients and family members.
AB  - AIMS: Genetic testing for maturity-onset diabetes of the young (MODY) facilitates
      a correct diagnosis, enabling treatment optimization and allowing monitoring of
      asymptomatic family members. To date, the majority of people with MODY remain
      undiagnosed. To identify patients' needs and areas for improving care, this study
      explores the experiences of patients and family members who have been genetically
      tested for MODY. METHODS: Fourteen semi-structured interviews with patients and
      the parents of patients, and symptomatic and asymptomatic family members were
      conducted. Atlas.ti was used for thematic analysis. RESULTS: Most people with
      MODY were initially misdiagnosed with Type 1 or Type 2 diabetes; they had been
      seeking for the correct diagnosis for a long time. Reasons for having a genetic
      test included reassurance, removing the uncertainty of developing diabetes (in
      asymptomatic family members) and informing relatives. Reasons against testing
      were the fear of genetic discrimination and not having symptoms. Often a positive
      genetic test result did not come as a surprise. Both patients and family members
      were satisfied with the decision to get tested because it enabled them to adjust
      their lifestyle and treatment accordingly. All participants experienced a lack of
      knowledge of MODY among healthcare professionals, in their social environment and
      in patient organizations. Additionally, problems with the reimbursement of
      medical expenses were reported. CONCLUSIONS: Patients and family members are
      generally positive about genetic testing for MODY. More education of healthcare
      professionals and attention on the part of diabetes organizations is needed to
      increase awareness and optimize care and support for people with MODY.

PMID- 25763775
TI  - A Novel Microsensor for Measuring Angular Distribution of Radiative Intensity.
AB  - This article presents the design, construction and characterization of a novel
      type of light probe for measuring the angular radiance distribution of light
      fields. The differential acceptance angle (DAA) probe can resolve the
      directionality of a light field in environments with steep light gradients, such
      as microbial mats, without the need to remove, reorient, and reinsert the probe,
      a clear advantage over prior techniques. The probe consists of an inner
      irradiance sensor inside a concentric, moveable light-absorbing sheath. The
      radiative intensity in a specific zenith direction can be calculated by comparing
      the irradiance onto the sensor at different acceptance angles. We used this probe
      to measure the angular radiance distribution of two sample light fields, and
      observed good agreement with a conventional radiance probe. The DAA probe will
      aid researchers in understanding light transfer physics in dense microbial
      communities and expedite validation of numerical radiative transfer models for
      these environments. 

PMID- 25763776
TI  - Reverse Trendelenburg position is a safer technique for lowering central venous
      pressure without decreasing blood pressure than clamping of the inferior vena
      cava below the liver.
AB  - BACKGROUND: Bleeding remains an important intraoperative complication in patients
      who undergo hepatectomy. It is generally believed that a reduction in central
      venous pressure will decrease bleeding from the hepatic venous system. To our
      knowledge, however, no study has compared the effectiveness of these techniques
      for controlling bleeding. So we compared the effectiveness of central venous
      pressure control techniques, such as infrahepatic inferior vena cava clamping,
      changes in surgical position of the patient, and hypoventilation anesthesia, for
      lowering central venous pressure. METHODS: The study group comprised 50 patients
      who underwent hepatectomy in our department from 2012 through 2013. A central
      venous catheter was inserted into the right internal jugular vein, and the tip
      was placed in the superior vena cava. A transducer was placed along the mid
      axillary line of the left side of the chest. After opening the abdomen, changes
      in central venous pressure were measured during inferior vena cava clamping, the
      reverse Trendelenburg position, the Trendelenburg position, and hypoventilation
      anesthesia. The inclination relative to the transducer, as measured with an
      inclinometer, was -10 degrees for the Trendelenburg position and +10 degrees for
      the reverse Trendelenburg position. The tidal volume was set at 10 mL/kg during
      conventional anesthesia and 5 mL/kg during hypoventilation anesthesia. RESULTS:
      The mean central venous pressure was 8.0 cm H(2)O in the supine position during
      conventional anesthesia, 5.0 cm H(2)O during inferior vena cava clamping, 5.6 cm
      H(2)O during reverse Trendelenburg position, 10.6 cm H(2)O during Trendelenburg
      position, and 7.6 cm H(2)O during hypoventilation anesthesia. The mean central
      venous pressure during inferior vena cava clamping and reverse Trendelenburg
      position was significantly lower than that during supine position (P = 0.0017 and
      P = 0.0231, respectively). The mean central venous pressure during
      hypoventilation anesthesia was not significantly lower than that during supine
      position (P = 0.9934). Mean systolic blood pressure was significantly decreased
      during inferior vena cava clamping (P = 0.0024), but not during reverse
      Trendelenburg position (P = 0.6344). CONCLUSIONS: Reverse Trendelenburg position
      decreased central venous pressure without significantly decreasing the systolic
      blood pressure, suggesting that it is possible to perform hepatectomy with
      reverse Trendelenburg position more safely than with inferior vena cava clamping.

PMID- 25763777
TI  - Early-onset axonal pathology in a novel P301S-Tau transgenic mouse model of
      frontotemporal lobar degeneration.
AB  - AIM: Tau becomes hyperphosphorylated in Alzheimer's disease (AD) and
      frontotemporal lobar degeneration (FTLD-tau), resulting in functional deficits of
      neurones, neurofibrillary tangle (NFT) formation and eventually dementia.
      Expression of mutant human tau in the brains of transgenic mice has produced
      different lines that recapitulate various aspects of FTLD-tau and AD. In this
      study, we characterized the novel P301S mutant tau transgenic mouse line,
      TAU58/2. METHODS: Both young and aged TAU58/2 mice underwent extensive motor
      testing, after which brain tissue was analysed with immunohistochemistry, silver
      staining, electron microscopy and Western blotting. Tissue from various FTLD
      subtypes and AD patients was also analysed for comparison. RESULTS: TAU58/2 mice
      presented with early-onset motor deficits, which became more pronounced with age.
      Throughout the brains of these mice, tau was progressively hyperphosphorylated
      resulting in increased NFT formation with age. In addition, frequent axonal
      swellings that stained intensively for neurofilament (NF) were present in young
      TAU58/2 mice prior to NFT formation. Similar axonal pathology was also observed
      in human FTLD-tau and AD. Interestingly, activated microglia were found in close
      proximity to neurones harbouring transgenic tau, but were not associated with NF
      positive axonal swellings. CONCLUSIONS: In TAU58/2 mice, early tau pathology
      induces functional deficits of neurones associated with NF pathology. This
      appears to be specific to tau, as similar changes are observed in FTLD-tau, but
      not in FTLD with TDP-43 inclusions. Therefore, TAU58/2 mice recapitulate aspects
      of human FTLD-tau and AD pathology, and will become instrumental in studying
      disease mechanisms and therapeutics in the future.

PMID- 25763778
TI  - Transcription factor and microRNA interactions in lung cells: an inhibitory link
      between NK2 homeobox 1, miR-200c and the developmental and oncogenic factors Nfib
      and Myb.
AB  - BACKGROUND: The transcription factor NK2 homeobox 1 (Nkx2-1) plays essential
      roles in epithelial cell proliferation and differentiation in mouse and human
      lung development and tumorigenesis. A better understanding of genes and pathways
      downstream of Nkx2-1 will clarify the multiple roles of this critical lung
      factor. Nkx2-1 regulates directly or indirectly numerous protein-coding genes;
      however, there is a paucity of information about Nkx2-1-regulated microRNAs
      (miRNAs). METHODS AND RESULTS: By miRNA array analyses of mouse epithelial cell
      lines in which endogenous Nkx2-1 was knocked-down, we revealed that 29 miRNAs
      were negatively regulated including miR-200c, and 39 miRNAs were positively
      regulated by Nkx2-1 including miR-1195. Mouse lungs lacking functional
      phosphorylated Nkx2-1 showed increased expression of miR-200c and alterations in
      the expression of other top regulated miRNAs. Moreover, chromatin
      immunoprecipitation assays showed binding of NKX2-1 protein to regulatory regions
      of these miRNAs. Promoter reporter assays indicated that 1kb of the miR-200c 5'
      flanking region was transcriptionally active but did not mediate Nkx2-1-
      repression of miR-200c expression. 3'UTR reporter assays support a direct
      regulation of the predicted targets Nfib and Myb by miR-200c. CONCLUSIONS: These
      studies suggest that Nkx2-1 controls the expression of specific miRNAs in lung
      epithelial cells. In particular, we identified a regulatory link between Nkx2-1,
      the known tumor suppressor miR-200c, and the developmental and oncogenic
      transcription factors Nfib and Myb, adding new players to the regulatory
      mechanisms driven by Nkx2-1 in lung epithelial cells that may have implications
      in lung development and tumorigenesis.

PMID- 25763780
TI  - Nursing Students' Experience of Bullying: Prevalence, Impact, and Interventions.
AB  - Studies examining nursing students' unique experience of bullying are
      increasingly evident. This article explores national and international literature
      over the past decade on prevalence rates, potential impact on nursing students,
      and relevance to socialization to the profession of nursing. Historical
      considerations are provided along with policies and interventions to empower
      nursing leaders, academicians, clinicians, and students to prevent or minimize
      the destructive nature of bullying. 

PMID- 25763781
TI  - Effects of an Experiential Learning Simulation Design on Clinical Nursing
      Judgment Development.
AB  - Simulation design should be theory based and its effect on outcomes evaluated.
      This study (1) applied a model of experiential learning to design a simulation
      experience, (2) examined how this design affected clinical nursing judgment
      development, and (3) described the relationship between clinical nursing judgment
      development and student performance when using the experiential learning design.
      Findings suggest that using an experiential learning simulation design results in
      more highly developed nursing judgment and competency in simulation performance. 

PMID- 25763779
TI  - Tendon mechanobiology: Current knowledge and future research opportunities.
AB  - Tendons mainly function as load-bearing tissues in the muscloskeletal system;
      transmitting loads from muscle to bone. Tendons are dynamic structures that
      respond to the magnitude, direction, frequency, and duration of physiologic as
      well as pathologic mechanical loads via complex interactions between cellular
      pathways and the highly specialized extracellular matrix. This paper reviews the
      evolution and current knowledge of mechanobiology in tendon development,
      homeostasis, disease, and repair. In addition, we review several novel
      mechanotransduction pathways that have been identified recently in other tissues
      and cell types, providing potential research opportunities in the field of tendon
      mechanobiology. We also highlight current methods, models, and technologies being
      used in a wide variety of mechanobiology research that could be investigated in
      the context of their potential applicability for answering some of the
      fundamental unanswered questions in this field. The article concludes with a
      review of the major questions and future goals discussed during the recent
      ORS/ISMMS New Frontiers in Tendon Research Conference held on September 10 and
      11, 2014 in New York City.

PMID- 25763782
TI  - The power and potential of positive mentoring.

PMID- 25763783
TI  - Reduced immune activation during tenofovir-emtricitabine therapy in HIV-negative
      individuals.
AB  - BACKGROUND: Elevated immune activation is associated with an increased risk of
      HIV acquisition. Tenofovir (TFV) has immunomodulatory properties in vitro, but
      how this extends in vivo remains unknown. METHODS: HIV-negative adults received
      daily coformulated TFV disoproxil fumarate 300 mg/emtricitabine (FTC) 200 mg for
      30 days followed by a 30-day washout. Markers of T-cell activation, inflammation,
      and cytokines were measured before drug and on days 30 (on drug) and 60 (30-day
      washout). Data were analyzed using one-way analysis of variance/pairwise
      comparisons. Intracellular disposition of TFV-diphosphate and FTC-triphosphate in
      CD4 and CD8 T-cells and monocytes was characterized, and the relationship with
      immune activation was evaluated using Pearson's correlation coefficient. RESULTS:
      T-cell activation was available in 19 participants. CD38/HLA-DR coexpression on
      CD8 T-cells decreased from baseline to day 30 (3.97% vs. 2.71%; P = 0.03) and day
      60 (3.97% vs. 2.41%; P = 0.008). Soluble CD27 decreased from baseline to day 60
      (184.1 vs. 168.4 pg/mL; P = 0.001). Cytokines and inflammation markers were not
      significantly different. TFV-diphosphate and FTC-triphosphate were approximately
      4-fold higher in monocytes vs. CD4 and CD8 T-cells but neither correlated with
      activation markers. CONCLUSIONS: TFV disoproxil fumarate/FTC therapy was
      associated with decreased T-cell activation in HIV-negative adults, which could
      contribute to the antiviral effect of pre-exposure prophylaxis (NCT01040091;
      www.clinicaltrials.gov).

PMID- 25763784
TI  - Effect of hormonal contraception on the function of plasmacytoid dendritic cells
      and distribution of immune cell populations in the female reproductive tract.
AB  - OBJECTIVE: Epidemiological evidence suggests an association between the use of
      hormonal contraception and an increased risk of acquiring sexually transmitted
      diseases including HIV-1. We sought to elucidate the biological mechanisms
      underlying the effect of hormonal contraception on the immune system. DESIGN:
      Cross-sectional study. METHODS: To delineate the biological mechanisms underlying
      the effect of hormonal contraceptives on the immune system, we analyzed the
      functional capacity of circulating plasmacytoid dendritic cells (pDCs), the
      distribution of vaginal immune cell populations, and the systemic and genital
      levels of immune mediators in women using depot medroxyprogesterone acetate
      (DMPA), NuvaRing, or combined oral contraceptives (COC). RESULTS: The use of DMPA
      or NuvaRing was associated with reduced capacity of circulating pDCs to produce
      interferon (IFN)-alpha and tumor necrosis (TNF-alpha) in response to TLR-9
      stimulation. Systemic levels of IFN-alpha and cervicovaginal fluid levels of IFN
      alpha, CXCL10, monocyte chemotactic protein-1, and granulocyte-colony stimulating
      factor were significantly lower in DMPA users compared to control volunteers not
      using hormonal contraception. The density of CD207 Langerhans cells in the
      vaginal epithelium was reduced in NuvaRing and combined oral contraceptive users
      but not in DMPA users. CONCLUSIONS: The presented evidence suggests that the use
      of some types of hormonal contraception is associated with reduced functional
      capacity of circulating pDCs and altered immune environment in the female
      reproductive tract.

PMID- 25763786
TI  - Risk factors for HCV acquisition among HIV-positive MSM in Belgium.
AB  - OBJECTIVE: To better understand risk factors for the sexual transmission of
      hepatitis C viral (HCV) infection among men who have sex with men (MSM). DESIGN:
      Case-control study among HIV-infected MSM, attending AIDS Reference Centers in
      Belgium. METHODS: Cases were HIV-infected MSM who were diagnosed with HCV between
      January 2010 and December 2013. For each case, 2 controls were randomly selected
      among the HIV-positive MSM who tested negative for HCV around the same time as
      the cases were identified. Consenting participants were interviewed with a
      questionnaire on risk factors. Medical records were abstracted to document past
      episodes of sexually transmitted infections (STIs). Associations between HCV
      infection and risk factors were explored using bivariate analysis followed by
      multiple logistic regression analysis. RESULTS: A total of 52 cases and 90
      controls were recruited. In multivariate analysis, douching before anal
      intercourse [adjusted odds ratio (AOR) = 9.84, 95% CI: 2.26 to 42.78], fisting
      (AOR = 3.54, 95% CI: 1.31 to 9.57), having intercourse with HIV-positive men (AOR
      = 5.51, 95% CI: 1.87 to 16.20), and a documented gonorrhoea or chlamydial
      infection in the year before inclusion in the study (AOR = 4.50, 95% CI: 1.11 to
      18.31) were independently associated with incident HCV infection. CONCLUSIONS:
      Our study confirmed fisting and suffering from other STIs as risk factors for HCV
      and suggested an increased risk of HCV associated with serosorting. Furthermore,
      we identified anal douching as being associated with HCV infection. The role that
      douching plays in the acquisition of HCV infection and other STIs requires
      further research, as well as the effect of serosorting on STI transmission.

PMID- 25763787
TI  - Brief report: Mobility and circular migration in Lesotho: implications for
      transmission, treatment, and control of a severe HIV epidemic.
AB  - We analyzed georeferenced data on mobility and HIV infection from the 2009
      Demographic and Health Survey of Lesotho. We found ~50% of the population
      traveled in the preceding year. By constructing gender-specific mobility maps, we
      discovered that travel is highest in the urban areas bordering South Africa and
      in the mountainous interior of the country. For both genders, increased mobility
      was associated with increased levels of "recent" sexual behavior. Notably,
      mobility was only associated with an increased risk of HIV infection for men who
      traveled frequently. We discuss the implications of our results for designing
      effective treatment programs and HIV interventions. 

PMID- 25763788
TI  - Evidence of cell-fate conversion from hepatocytes to cholangiocytes in the
      injured liver: in-vivo genetic lineage-tracing approaches.
AB  - PURPOSE OF REVIEW: Recently, it has been suggested that hepatocytes can
      potentially convert their fate into that of cholangiocytes when the liver
      receives an injury. This review concisely summarizes these new findings,
      especially those obtained in studies using cell-lineage tracing methods. RECENT
      FINDINGS: Recent advances in technologies using mutant mice with a tamoxifen
      inducible Cre/loxP system have allowed heritable labeling of a particular type of
      cell and enabled us to follow the fate of their progeny. This is generally known
      as 'genetic lineage-tracing', and has been applied in various studies that
      require tracking of the fate of cells in living mice. Previous studies using
      these methods have revealed that hepatocytes themselves can give rise to
      cholangiocytes through Notch-mediated cell-fate conversion from hepatocytes to
      cholangiocytes in injured liver tissue and at the onset of liver cancer. SUMMARY:
      Intensive studies using in-vivo genetic lineage-tracing approaches have provided
      new insights into the nature of cellular identity and plasticity in the liver,
      which will contribute to the development of new therapeutic strategies for liver
      diseases.

PMID- 25763789
TI  - Fibroblast growth factor receptor 2 fusions as a target for treating
      cholangiocarcinoma.
AB  - PURPOSE OF REVIEW: This review will cover the role of the fibroblast growth
      factor pathway in the pathogenesis, targeted therapy potential and prognostic
      value in patients with cholangiocarcinoma (CCA). RECENT FINDINGS: Recent studies
      that have identified fibroblast growth factor receptor 2 (FGFR2) fusions,
      prognostic implications of FGFR2 fusions, treatment strategies that target FGFR2
      in CCA and future directions for understanding and targeting the FGFR2 pathway in
      this disease, will be discussed. SUMMARY: Understanding the role of the FGFR2
      pathway as a disease pathogenetic mechanism and the ability to develop targeted
      therapies and diagnostics surrounding this concept are critical elements toward
      developing novel targeted approaches in CCA.

PMID- 25763791
TI  - Personalized Medicine-Disregarding the Obvious: Analysis of Trends Among Articles
      Published on "Personalized Medicine".

PMID- 25763790
TI  - Renal dysfunction in cirrhosis.
AB  - PURPOSE OF REVIEW: Renal dysfunction causes significant morbidity in cirrhotic
      patients. Diagnosis is challenging because it is based on serum creatinine, which
      is used to calculate estimated glomerular filtration rate, which itself is not an
      ideal measure of renal function in patients with cirrhosis. Finding the exact
      cause of renal injury in patients with cirrhosis remains problematic due to the
      limitations of the current diagnostic tests. The purpose of this review is to
      highlight studies used to diagnose renal dysfunction in patients with renal
      dysfunction and review current treatments. RECENT FINDINGS: New diagnostic
      criteria and classification of renal dysfunction, especially for acute kidney
      injury (AKI), have been proposed in hopes of optimizing treatment and improving
      outcomes. New biomarkers that help to differentiate structural from functional
      AKI in cirrhotic patients have been developed, but require further investigation.
      Vasoconstrictors are the most commonly recommended treatment of hepatorenal
      syndrome (HRS). Given the high mortality in patients with type 1 HRS, all
      patients with HRS should be evaluated for liver transplantation. When renal
      dysfunction is considered irreversible, combined liver-kidney transplantation is
      advised. SUMMARY: Development of new biomarkers to differentiate the different
      types of AKI in cirrhosis holds promise. Early intervention in cirrhotic patients
      with renal dysfunction offers the best hope of improving outcomes.

PMID- 25763792
TI  - A Randomized Controlled Study to Examine the Effect of a Lifestyle Modification
      Program in OSA.
AB  - BACKGROUND: Obesity is an important risk factor for OSA. This study aimed to
      assess the effect of weight reduction through a lifestyle modification program
      (LMP) on patients with moderate to severe OSA. METHODS: This was a parallel
      group, randomized controlled trial. Altogether, 104 patients with moderate to
      severe OSA diagnosed on portable home sleep monitoring were randomized to receive
      a dietician-led LMP or usual care for 12 months. The primary outcome was
      reduction of apnea-hypopnea index (AHI) at 12 months as assessed by portable home
      sleep monitoring. RESULTS: In the intention-to-treat analysis (ITT), LMP (n = 61)
      was more effective in reducing AHI from baseline (16.9% fewer events in the LMP
      group vs 0.6% more events in the control group, P = .011). LMP was more effective
      in reducing BMI (-1.8 kg/m2, 6.0% of the initial BMI; -0.6 kg/m2, 2.0% of the
      initial BMI in control group; P < .001). The reduction in daytime sleepiness as
      assessed by Epworth Sleepiness Scale was not significant in ITT but was more in
      the LMP group (-3.5 in the LMP group vs -1.1 in the control group, P = .004) by
      treatment per protocol analysis. There was modest improvement in mental health in
      the Short Form Health Survey. Eating behavior was improved with increased intake
      of protein and fiber. These changes were observed 4 months after the initial
      intensive diet counseling and persisted at 12 months. CONCLUSIONS: LMP was
      effective in reducing the severity of OSA and daytime sleepiness. The beneficial
      effect was sustained in 12 months. TRIAL REGISTRY: ClinicalTrials.gov; No.:
      NCT01384760; URL: www.clinicaltrials.gov.

PMID- 25763793
TI  - Cross-cultural adaptation, evaluation and validation of the Spouse Response
      Inventory: a study protocol.
AB  - INTRODUCTION: Since the response of spouses has been proven to be an important
      reinforcement of pain behaviour and disability it has been addressed in research
      and therapy. Fordyce suggested pain behaviour and well behaviour be considered in
      explaining suffering in chronic pain patients. Among existing instruments
      concerning spouse's responses the aspect of well behaviour has not been examined
      so far. The SRI (Spouse Response Inventory) tries to consider pain behaviour and
      well behaviour and appears to be acceptable because of its brevity and close
      proximity to daily language. The aim of the study is the translation into German,
      followed by evaluation and validation, of the SRI on a German sample of patients
      with chronic pain. METHODS AND ANALYSES: The study is comprehensively designed:
      initially, the focus will lie on the translation of the instrument following the
      guidelines for cross-cultural translation and adaptation and evaluation of the
      German version according to the source study. Subsequently, a validation
      referring to predictive, incremental and construct validation will be conducted
      using instruments based on similar or close but different constructs. Evaluation
      of the resulting SRI-G (SRI-German) will be conducted on a sample of at least 30
      patients with chronic pain attending a comprehensive pain centre. For validation
      at least 120 patients with chronic headache, back pain, cancer related pain and
      somatoform pain disorder shall be included, for a total of 480 patients. Separate
      analyses according to specific pain diagnoses will be performed to ensure
      psychometric property, interpretability and control of diagnosis of specific
      limitations. Analyses will include comprehensive investigation of psychometric
      property of the scale by hierarchical regression analyses, correlation analyses,
      multivariate analysis of variance and exploratory factor analyses (SPSS). ETHICS:
      The study protocol was approved by the Ethics Committee of the University of
      Dresden (EK 335 122008) based on the Helsinki declaration.

PMID- 25763794
TI  - Term perinatal mortality audit in the Netherlands 2010-2012: a population-based
      cohort study.
AB  - OBJECTIVE: To assess the implementation and first results of a term perinatal
      internal audit by a standardised method. DESIGN: Population-based cohort study.
      SETTING: All 90 Dutch hospitals with obstetric/paediatric departments linked to
      community practices of midwives, general practitioners in their attachment areas,
      organised in perinatal cooperation groups (PCG). POPULATION: The population
      consisted of 943 registered term perinatal deaths occurring in 2010-2012 with
      detailed information, including 707 cases with completed audit results. MAIN
      OUTCOME MEASURES: Participation in the audit, perinatal death classification,
      identification of substandard factors (SSF), SSF in relation to death, conclusive
      recommendations for quality improvement in perinatal care and antepartum risk
      selection at the start of labour. RESULTS: After the introduction of the
      perinatal audit in 2010, all PCGs participated. They organised 645 audit
      sessions, with an average of 31 healthcare professionals per session. Of all 1102
      term perinatal deaths (2.3/1000) data were registered for 86% (943) and
      standardised anonymised audit results for 64% (707). In 53% of the cases at least
      one SSF was identified. Non-compliance to guidelines (35%) and deviation from
      usual professional care (41%) were the most frequent SSF. There was a (very)
      probable relation between the SSF and perinatal death for 8% of all cases. This
      declined over the years: from 10% (n=23) in 2010 to 5% (n=10) in 2012 (p=0.060).
      Simultaneously term perinatal mortality decreased from 2.3 to 2.0/1000 births
      (p<0.00001). Possibilities for improvement were identified in the organisation of
      care (35%), guidelines or usual care (19%) and in documentation (15%). More
      pregnancies were antepartum selected as high risk, 70% in 2010 and 84% in 2012
      (p=0.0001). CONCLUSIONS: The perinatal audit is implemented nationwide in all
      obstetrical units in the Netherlands in a short time period. It is possible that
      the audit contributed to the decrease in term perinatal mortality.

PMID- 25763795
TI  - Audiologists' preferences for patient-centredness: a cross-sectional
      questionnaire study of cross-cultural differences and similarities among
      professionals in Portugal, India and Iran.
AB  - OBJECTIVE: Patient-centredness has become an important aspect of health service
      delivery; however, there are a limited number of studies that focus on this
      concept in the domain of hearing healthcare. The objective of this study was to
      examine and compare audiologists' preferences for patient-centredness in
      Portugal, India and Iran. DESIGN: The study used a cross-sectional survey design
      with audiologists recruited from three different countries. PARTICIPANTS: A total
      of 191 fully-completed responses were included in the analysis (55 from Portugal,
      78 from India and 58 from Iran). MAIN OUTCOME MEASURE: The Patient-Practitioner
      Orientation Scale (PPOS). RESULTS: PPOS mean scores suggest that audiologists
      have a preference for patient-centredness (ie, mean of 3.6 in a 5-point scale).
      However, marked differences were observed between specific PPOS items suggesting
      these preferences vary across clinical situations. A significant level of
      difference (p<0.001) was found between audiologists' preferences for patient
      centredness in three countries. Audiologists in Portugal had a greater preference
      for patient-centredness when compared to audiologists in India and Iran, although
      no significant differences were found in terms of age and duration of experience
      among these sample populations. CONCLUSIONS: There are differences and
      similarities in audiologists' preferences for patient-centredness among
      countries. These findings may have implications for the training of professionals
      and also for clinical practice in terms of optimising hearing healthcare across
      countries.

PMID- 25763796
TI  - Sexual violence and neonatal outcomes: a Norwegian population-based cohort study.
AB  - OBJECTIVE: The objective of this study was to explore the association between
      sexual violence and neonatal outcomes. DESIGN: National cohort study. SETTING:
      Women were recruited to the Norwegian Mother and Child Cohort Study (MoBa) while
      attending routine ultrasound examinations from 1999 to 2008. POPULATION: A total
      of 76 870 pregnant women. METHODS: Sexual violence and maternal characteristics
      were self-reported in postal questionnaires during pregnancy. Neonatal outcomes
      were retrieved from the Medical Birth Registry of Norway (MBRN). Risk estimations
      were performed with linear and logistic regression analysis. OUTCOME MEASURES:
      gestational age at birth, birth weight, preterm birth (PTB), low birth weight
      (LBW) and small for gestational age (SGA). RESULTS: Of 76 870 women, 18.4%
      reported a history of sexual violence. A total of 4.7% delivered prematurely,
      2.7% had children with a birth weight <2500 g and 8.1% children were small for
      their gestational age. Women reporting moderate or severe sexual violence (rape)
      had a significantly reduced gestational length (2 days) when the birth was
      provider-initiated in an analysis adjusted for age, parity, education, smoking,
      body mass index and mental distress. Those exposed to severe sexual violence had
      a significantly reduced gestational length of 0.51 days with a spontaneous start
      of birth. Crude estimates showed that severe sexual violence was associated with
      PTB, LBW and SGA. When controlling for the aforementioned sociodemographic and
      behavioural factors, the association was no longer significant. CONCLUSIONS:
      Sexual violence was not associated with adverse neonatal outcomes. Moderate and
      severe violence had a small but significant effect on gestational age; however,
      the clinical influence of this finding is most likely limited. Women exposed to
      sexual violence in this study reported more of the sociodemographic and
      behavioural factors associated with PTB, LBW and SGA compared with non-abused
      women.

PMID- 25763797
TI  - Rationale and design of the Pan African Pulmonary hypertension Cohort (PAPUCO)
      study: implementing a contemporary registry on pulmonary hypertension in Africa.
AB  - INTRODUCTION: Pulmonary hypertension (PH) is a devastating, progressive disease
      with increasingly debilitating symptoms and usually shortened overall life
      expectancy due to a narrowing of the pulmonary vasculature and consecutive right
      heart failure. Little is known about PH in Africa, but limited reports suggest
      that PH is more prevalent in Africa compared with developed countries due to the
      high prevalence of risk factors in the region. METHODS AND ANALYSIS: A
      multinational multicentre registry-type cohort study was established and tailored
      to resource-constraint settings to describe disease presentation, disease
      severity and aetiologies of PH, comorbidities, diagnostic and therapeutic
      management, and the natural course of PH in Africa. PH will be diagnosed by
      specialist cardiologists using echocardiography (right ventricular systolic
      pressure >35 mm Hg, absence of pulmonary stenosis and acute right heart failure),
      usually accompanied by shortness of breath, fatigue, peripheral oedema and other
      cardiovascular symptoms, ECG and chest X-ray changes in keeping with PH as per
      guidelines (European Society of Cardiology and European Respiratory Society
      (ESC/ERS) guidelines). Additional investigations such as a CT scan, a
      ventilation/perfusion scan or right heart catheterisation will be performed at
      the discretion of the treating physician. Functional tests include a 6 min walk
      test and the Karnofsky Performance Score. The WHO classification system for PH
      will be applied to describe the different aetiologies of PH. Several substudies
      have been implemented within the registry to investigate specific types of PH and
      their outcome at up to 24 months. Data will be analysed by an independent
      institution following a data analyse plan. ETHICS AND DISSEMINATION: All local
      ethics committees of the participating centres approved the protocol. The data
      will be disseminated through peer-reviewed journals at national and international
      conferences and public events at local care providers.

PMID- 25763798
TI  - Acute Temporal Profiles of Serum Levels of UCH-L1 and GFAP and Relationships to
      Neuronal and Astroglial Pathology following Traumatic Brain Injury in Rats.
AB  - A number of potential traumatic brain injury (TBI) biomarkers have been proposed
      and evaluated in the laboratory and clinic. This study investigated the temporal
      profile of circulating biomarkers of astrocytic and neuronal injury over the
      first 24 h and relevant histopathological changes after experimental moderate
      TBI. Twenty male rats were randomly assigned to either moderate parasagittal
      fluid percussion or sham injury. Blood serum samples were collected 2 d prior to
      TBI (baseline) and at 3, 6, and 24 h after TBI. A single cerebrospinal fluid
      (CSF) sample was collected from the cisterna magna 24 h after TBI, followed by
      euthanasia and brain harvesting for histology. Serum and CSF samples were
      analyzed for neuronal (ubiquitin carboxy-terminal hydrolase L1 [UCH-L1]) and
      astroglial (glial fibrillary acidic protein [GFAP]) protein levels using enzyme
      linked immunosorbent assay. Brain histology included GFAP immunostaining and
      Fluoro-Jade histofluorescence. Serum and CSF levels of GFAP were near zero in
      sham animals. Serum GFAP levels were significantly elevated at 3 and 6 h post
      TBI, compared with baseline and time-matched sham values, while UCH-L1 was
      significantly elevated only at 3 h post-TBI. Both CSF GFAP and UCH-L1 at 24 h
      post-TBI were significantly elevated, compared with sham. GFAP
      immunohistochemistry and FJ histofluorescence of degenerating neurons were
      performed in the same animals after 24 h survival. Histology revealed
      characteristic acute neuronal degeneration in the ipsilateral hippocampus and
      parietal cortex and reduction in GFAP immunostaining in areas of neuronal cell
      loss. The data provide evidence of a causal relationship between TBI-induced
      acute brain pathology and circulating neuronal and glial markers, further
      demonstrating their role as candidate markers for TBI. Studies of relative
      changes in biomarker levels in CSF and serum suggest that different mechanisms
      may underlie the transport and/or clearance of UCH-L1 and GFAP in these two
      compartments. 

PMID- 25763799
TI  - An Exploratory Study of Reading Comprehension in College Students After Acquired
      Brain Injury.
AB  - PURPOSE: This exploratory study builds on the small body of existing research
      investigating reading comprehension deficits in college students with acquired
      brain injury (ABI). METHOD: Twenty-four community college students with ABI
      completed a battery of questionnaires and standardized tests to characterize self
      perceptions of academic reading ability, performance on a standardized reading
      comprehension measure, and a variety of cognitive functions of this population.
      Half of the participants in the sample reported traumatic brain injury (n = 12)
      and half reported nontraumatic ABI (n = 12). RESULTS: College students with both
      traumatic and nontraumatic ABI cite problems with reading comprehension and
      academic performance postinjury. Mean performance on a standardized reading
      measure, the Nelson-Denny Reading Test (Brown, Fischo, & Hanna, 1993), was low to
      below average and was significantly correlated with performance on the Speed and
      Capacity of Language Processing Test (Baddeley, Emslie, & Nimmo-Smith, 1992).
      Injury status of traumatic versus nontraumatic ABI did not differentiate results.
      Regression analysis showed that measures of verbal attention and suppression
      obtained from the California Verbal Language Test-II (Delis, Kramer, Kaplan, &
      Ober, 2000) predicted total scores on the Nelson-Denny Reading Test. CONCLUSIONS:
      College students with ABI are vulnerable to reading comprehension problems.
      Results align with other research suggesting that verbal attention and
      suppression problems may be contributing factors.

PMID- 25763800
TI  - Short-term effect of vaginal erbium laser on the genitourinary syndrome of
      menopause.
AB  - AIM: In this study we evaluated the short term effects of vaginal erbium laser
      (VEL) in the treatment of postmenopausal women (PMW) suffering from genitourinary
      syndrome of menopause (GSM). METHODS: Sixty-five PMW were evaluated before and
      after VEL treatment (1 treatment every 30 days, for 3 months). GSM symptoms were
      evaluated either with subjective (Visual Analog Scale, VAS) and objective
      (Vaginal Health Index Score, VHIS) measures. In addition, in 21 of these PMW
      suffering from mild-moderate stress urinary incontinence (SUI), the degree of
      incontinence was evaluated with the International Consultation on Incontinence
      Questionnaire - Urinary Incontinence Short Form (ICIQ-UI SF) before and after VEL
      treatments. RESULTS: VEL treatment induced a significant decrease of VAS of both
      vaginal dryness, dyspareunia (P<0.01) and a significant (P<0.01) increase of
      VHIS). In addition, VEL treatment induced a significant (P<0.01) improvement of
      ICIQ-SF scores in PMW suffering from SUI. VEL was well tolerated with less than 2
      % of patients discontinuing treatment due to adverse events. CONCLUSION: VEL
      treatment significantly improves vaginal dryness, dyspareunia and mild-moderate
      SUI. Larger and long-term studies are needed to investigate the role of laser
      treatments in the management of GSM.

PMID- 25763801
TI  - Hyaluronic acid-chondroitin sulfate: a potential factor to select pure stress
      urinary incontinence in patients with interstitial cystitis/painful bladder
      syndrome and mixed incontinence symptoms.
AB  - AIM: Aim of the study was to validate the Hyaluronic acid-Chondroitin sulfate (HA
      CS) as ex adiuvantibus criteria to identified patients with urgency symptoms
      related to interstitial cystitis/painful bladder syndrome (IC/PBS) and to
      obtained a population of patients with pure stress urinary incontinence. METHODS:
      We retrospectively analysed clinical data of 17 patients with clinical suspect of
      IC/PBS, which received intravescical HA-CS to reduce pelvic pain and urgency
      symptoms waiting for surgical treatment for stress urinary incontinence. The main
      outcomes were reduction of urinary frequency, urgency, and bladder pain. RESULTS:
      Compared to baseline, a significant decrease in pain, urgency and frequency were
      observed. Of the 17 patients, 82.3% reported resolution of pain and urge symptoms
      and in patients with persistence of urge symptoms the urodynamic assessment
      showed an overactive bladder syndrome (OAB). CONCLUSION: HA-CS treatment induces
      an improvement in pain and urgency symptoms in patients with IC/PBS that referred
      also stress urinary incontinence. Therefore, HA-CS treatment could be use as
      clinical adjunctive parameter to select patients with pure stress urinary
      incontinence.

PMID- 25763802
TI  - Direct construction of fused indoles by gold-catalyzed cascade cyclization of
      conjugated diynes.
AB  - A gold-catalyzed cascade cyclization of aniline derivatives bearing a conjugated
      diyne moiety was developed. Following the 5-endo-dig indole formation, subsequent
      7-endo-dig cyclization predominated over 6-exo-dig cyclization to give the indole
      fused with a seven-membered ring in good yields. 

PMID- 25763803
TI  - Ni/Ti layered double hydroxide: synthesis, characterization and application as a
      photocatalyst for visible light degradation of aqueous methylene blue.
AB  - Visible light responsive 2 : 1 Ni/Ti layered double hydroxide (LDH) was
      synthesized by a single step hydrothermal route using commercially available
      Ni(NO3)2.6H2O, TiCl4 and urea. The material exhibited significant absorption in
      the visible range with a very narrow band gap (2.68 eV). This could be attributed
      to structural defects as confirmed by diffuse reflectance spectroscopy (DRS),
      photoluminescence (PL), X-ray diffraction (XRD) and X-ray photoelectron
      spectroscopy (XPS) measurements. FT-IR, TGA, DTA, DSC, HR-TEM and SEM-EDX
      measurements yielded information about structural aspects, thermal stability and
      surface morphology. Surface and pore characteristics of the material were
      obtained from the BET isotherm for N2 adsorption at 77 K. Zeta potential
      measurements were used to characterize the electrical properties of the surface
      while XPS revealed changes in surface states and oxygen deficiencies. The
      material was found to be an excellent photocatalyst for the degradation of
      aqueous methylene blue in visible light. The photocatalytic properties of the
      material were explained on the basis of the narrow band gap, the high surface
      area and the presence of surface defects. The photocatalytic activity improved in
      alkaline media [pH 11.0, catalyst load 15 mg in 200 ml dye solution, dye
      concentration 1 * 10(-6) M (= 0.3198 mg L(-1))] due to the electrostatic
      attractions between the dye cations and the negative charges on the Ni/Ti LDH
      surface. The catalytic activity was found to be higher than the common commercial
      catalysts like ZnO, ZnS, NiO, TiO2 and Degussa P25. The catalytic activity was
      retained even after five methylene blue degradation cycles, demonstrating that
      the LDH could be an important addition to the field of wastewater treatment. 

PMID- 25763804
TI  - An evaluation of geographic trends in the otolaryngology residency match: home is
      where the heart is.
AB  - IMPORTANCE: Securing an otolaryngology residency position has become an
      increasingly competitive endeavor in recent years. Recent studies have
      investigated the applicant criteria used by residency programs as part of the
      ranking process. However, to our knowledge, no studies have comprehensively
      investigated the role of geographic location in the match process. OBJECTIVE: To
      evaluate geographic trends in the otolaryngology national residency match
      process. DESIGN, SETTING, AND PARTICIPANTS: We conducted a cross-sectional
      examination of 56 otolaryngology residency programs including 810 residents to
      determine resident demographic information, including matriculated medical
      schools. MAIN OUTCOMES AND MEASURES: The geographic locations of residency
      programs and the residents' matriculated medical schools were evaluated for
      trends. Residents' program locations were compared with the locations of their
      medical schools of matriculation, and the numbers of residents attending a
      program affiliated with their medical schools were also identified. RESULTS:
      Overall, 810 residents were identified from the 56 programs included in our
      study. Of these, 169 residents (20.9%) attended the program affiliated with their
      medical school. The Midwest had the highest proportion of residents graduating
      from the affiliated medical school (25.7%), and the West had the lowest
      proportion (12.5%) (P = .008). A total of 473 residents attended a program within
      the same region as their medical school (58.4%). The South had the highest
      proportion of residents from the same region (68.2%), and the West had the lowest
      proportion (31.3%) (P < .001). CONCLUSIONS AND RELEVANCE: While it is not clear
      why a geographic bias was identified, a significant proportion of residents in
      our study attended a program in the same region as their medical school. This
      geographic association was strongest in the Midwest and South. Furthermore, a
      significant proportion of residents attended the program affiliated with their
      medical schools. This information is valuable to all future applicants as they
      choose where to apply, and to all residency programs as they decide how
      geographic location factors in to whom they decide to interview.

PMID- 25763805
TI  - Rhodium catalyzed C2-selective cyanation of indoles and pyrroles.
AB  - An efficient and general rhodium(III) catalyzed C2-selective cyanation of indoles
      and pyrroles was accomplished employing easily accessible and environmentally
      friendly cyanating reagent, NCTS. This methodology tolerates various functional
      groups, uses readily removable directing groups and allows the synthesis of
      various 2-cyanoindoles and pyrroles in good to excellent yield. 

PMID- 25763806
TI  - Comments on "Dosimetric study of fetal exposure to uniform magnetic fields at 50
      Hz" by Liorni et al.

PMID- 25763807
TI  - Nanostructured hybrid shells of r-GO/AuNP/m-TiO2 as highly active photocatalysts.
AB  - Nanostructured hybrid shells of r-GO/AuNP/m-TiO2 were synthesized using SiO2
      spheres as templates, followed by graphene oxide (GO) and Au nanoparticle (AuNP)
      deposition and TiO2 coating, and then post-treatments of template removal and
      calcination. Evaluation of their photocatalytic activity by degradation of
      Rhodamine B (RhB) under the irradiation of UV, visible light, and simulated
      daylight demonstrated the superior photocatalytic performance of the sandwich
      like hollow hybrid shells, which could be attributed to the porous nature of the
      hybrid shells and the enhanced charge separation and visible-light absorption of
      r-GO and AuNPs. 

PMID- 25763785
TI  - Cancer risk and use of protease inhibitor or nonnucleoside reverse transcriptase
      inhibitor-based combination antiretroviral therapy: the D: A: D study.
AB  - BACKGROUND: The association between combination antiretroviral therapy (cART) and
      cancer risk, especially regimens containing protease inhibitors (PIs) or
      nonnucleoside reverse transcriptase inhibitors (NNRTIs), is unclear. METHODS:
      Participants were followed from the latest of D:A:D study entry or January 1,
      2004, until the earliest of a first cancer diagnosis, February 1, 2012, death, or
      6 months after the last visit. Multivariable Poisson regression models assessed
      associations between cumulative (per year) use of either any cART or PI/NNRTI,
      and the incidence of any cancer, non-AIDS-defining cancers (NADC), AIDS-defining
      cancers (ADC), and the most frequently occurring ADC (Kaposi sarcoma, non-Hodgkin
      lymphoma) and NADC (lung, invasive anal, head/neck cancers, and Hodgkin
      lymphoma). RESULTS: A total of 41,762 persons contributed 241,556 person-years
      (PY). A total of 1832 cancers were diagnosed [incidence rate: 0.76/100 PY (95%
      confidence interval: 0.72 to 0.79)], 718 ADC [0.30/100 PY (0.28-0.32)], and 1114
      NADC [0.46/100 PY (0.43-0.49)]. Longer exposure to cART was associated with a
      lower ADC risk [adjusted rate ratio: 0.88/year (0.85-0.92)] but a higher NADC
      risk [1.02/year (1.00-1.03)]. Both PI and NNRTI use were associated with a lower
      ADC risk [PI: 0.96/year (0.92-1.00); NNRTI: 0.86/year (0.81-0.91)]. PI use was
      associated with a higher NADC risk [1.03/year (1.01-1.05)]. Although this was
      largely driven by an association with anal cancer [1.08/year (1.04-1.13)], the
      association remained after excluding anal cancers from the end point [1.02/year
      (1.01-1.04)]. No association was seen between NNRTI use and NADC [1.00/year (0.98
      1.02)]. CONCLUSIONS: Cumulative use of PIs may be associated with a higher risk
      of anal cancer and possibly other NADC. Further investigation of biological
      mechanisms is warranted.

PMID- 25763808
TI  - Mechanisms of reactions of sulfur hydride hydroxide: tautomerism, condensations,
      and C-sulfenylation and O-sulfenylation of 2,4-pentanedione.
AB  - The conformations, equilibrium structures, hydrogen bonds, and non-covalent
      interactions involved in the mechanisms of tautomerization, condensations, and C
      sulfenylation and O-sulfenylation of 2,4-pentanedione by sulfur hydride hydroxide
      (hydrogen thioperoxide, oxadisulfane, H-SOH) have been studied using BD(T),
      CCSD(T), and QCISD(T) with the cc-pVTZ basis set and using B3LYP, B3PW91, CAM
      B3LYP, PBE1PBE, PBEh1PBE, LC-omegaPBE, M06-2X, and omegaB97XD with the 6
      311+G(d,p) basis set. All levels of theory predict the sulfenyl (H-SOH) tautomer
      of hydrogen thioperoxide to be lower in energy than the sulfinyl (H2S?O)
      tautomer. Four reasonable mechanisms were considered for the tautomerization of
      the sulfenyl tautomer of hydrogen thioperoxide to the sulfinyl tautomer: a cyclic
      three-membered water-free transition state (TS, CCSD(T) activation energy barrier
      E(?) = 65.1 kcal/mol), a cyclic five-membered transition state with one water
      molecule (TSH2O, E(?) = 31.1 kcal/mol), a cyclic seven-membered transition state
      with two water molecules (TS2H2O, E(?) = 14.5 kcal/mol), and a cyclic nine
      membered transition state with three water molecules (TS3H2O, E(?) = 5.6
      kcal/mol). The mechanisms involve hydrogen-bonded reactant complexes and hydrogen
      bonded product complexes. The CCSD(T)-predicted energy barriers for the
      condensation of hydrogen thioperoxide to form thiosulfinic acid through
      transition states with zero, one, and two waters are E(?) = 42.0, 18.3, and 0
      kcal/mol, respectively. Mixed condensation reactions are predicted to afford
      organosulfur products and compounds containing sulfur-selenium bonds. Hydrogen
      thioperoxide is predicted to add to 2,4-pentanedione to form C-sulfenylated
      (sulfide, thioether) and O-sulfenylated (sulfenate ester) products. Similar
      mechanistic trends and reaction pathways are observed in the tautomerism,
      condensations, and C-sulfenylation and O-sulfenylation reactions of hydrogen
      thioperoxide. The water molecules set up proton relay networks (bridges) that
      reduce ring strain, generate favorable conformations for reactivity, lower energy
      barriers, and increase the numbers of stabilizing hydrogen bonds and nonbonding
      interactions. 

PMID- 25763809
TI  - Human telomeric RNA G-quadruplex response to point mutation in the G-quartets.
AB  - Many putative G-quadruplex forming sequences have been predicted to exist in the
      human genome and transcriptome. As these sequences are subject to point mutations
      or SNPs (single nucleotide polymorphisms) during the course of evolution, we
      attempt to understand impact of these mutations in context of RNA G-quadruplex
      formation using human telomeric RNA (TERRA) as a model sequence. Our studies
      suggest that G-quadruplex stability is sensitive to substitution of the guanines
      comprising G-quartets. While central G-quartet plays a crucial role in
      maintaining the DNA G-quadruplex stability as evident in literature, there is
      equal importance of three G-quartets in the stability of RNA quadruplex
      structure. The work here highlights the alterations in the G-quartet are
      detrimental to the integrity of overall RNA G-quadruplex structure. Furthermore,
      TmPyP4 molecules are shown to exhibit similar binding behavior toward telomeric
      RNA G-quadruplex harboring base substitutions employing CD titrations and
      isothermal titration calorimetry; well indicating that mutation does not
      influence TmPyP4 recognition ability as it affects the stability of RNA G
      quadruplex. Thus, our study implicates that mutation in G-quartets causes
      destabilization of RNA G-quadruplex without affecting its trans factor binding
      ability. 

PMID- 25763810
TI  - Study and modeling of the evolution of gas-liquid partitioning of hydrogen
      sulfide in model solutions simulating winemaking fermentations.
AB  - The knowledge of gas-liquid partitioning of aroma compounds during winemaking
      fermentation could allow optimization of fermentation management, maximizing
      concentrations of positive markers of aroma and minimizing formation of
      molecules, such as hydrogen sulfide (H2S), responsible for defects. In this
      study, the effect of the main fermentation parameters on the gas-liquid partition
      coefficients (Ki) of H2S was assessed. The Ki for this highly volatile sulfur
      compound was measured in water by an original semistatic method developed in this
      work for the determination of gas-liquid partitioning. This novel method was
      validated and then used to determine the Ki of H2S in synthetic media simulating
      must, fermenting musts at various steps of the fermentation process, and wine. Ki
      values were found to be mainly dependent on the temperature but also varied with
      the composition of the medium, especially with the glucose concentration.
      Finally, a model was developed to quantify the gas-liquid partitioning of H2S in
      synthetic media simulating must to wine. This model allowed a very accurate
      prediction of the partition coefficient of H2S: the difference between observed
      and predicted values never exceeded 4%.

PMID- 25763811
TI  - Training the teachers. The clinician-educator track of the University of
      Washington Pulmonary and Critical Care Medicine Fellowship Program.
AB  - The University of Washington was the first pulmonary and critical care medicine
      fellowship training program accredited by the Accreditation Council for Graduate
      Medical Education to create a dedicated clinician-educator fellowship track that
      has its own National Residency Matching Program number. This track was created in
      response to increasing demand for focused training in medical education in
      pulmonary and critical care. Through the Veterans Health Administration we
      obtained a stipend for a clinician-educator fellow to dedicate 12 months to
      training in medical education. This takes place predominantly in the second year
      of fellowship and is composed of several core activities: fellows complete the
      University of Washington's Teaching Scholars Program, a professional development
      program designed to train leaders in medical education; they teach in a variety
      of settings and receive feedback on their work from clinician-educator faculty
      and the learners; and they engage in scholarly activity, which may take the form
      of scholarship of teaching, integration, or investigation. Fellows are guided
      throughout this process by a primary mentor and a mentoring committee. Since
      funding became available in 2009, two of the three graduates to date have
      successfully secured clinician-educator faculty positions. Graduates uniformly
      believe that the clinician-educator track met their training goals better than
      the research-based track would have. 

PMID- 25763812
TI  - In situ imaging of interfacial precipitation of phosphate on Goethite.
AB  - Adsorption and subsequent immobilization of orthophosphate on iron oxides is of
      considerable importance in soil fertility and eutrophication studies. Here, in
      situ atomic force microscopy (AFM) has been used to probe the interaction of
      phosphate-bearing solutions with goethite, alpha-FeOOH, (010) cleavage surfaces.
      During the dissolution of goethite we observed simultaneous nucleation of
      nanoparticles (1.0-3.0 nm in height) of iron phosphate (Fe-P) phases at the
      earliest nucleation stages, subsequent aggregation to form secondary particles
      (about 6.0 nm in height) and layered precipitates under various pH values and
      ionic strengths relevant to acid soil solution conditions. The heterogeneous
      nucleation rates of Fe-P precipitates at phosphate concentrations ranging from
      5.0 to 50.0 mM were quantitatively defined. Enhanced goethite dissolution in the
      presence of high concentration NaCl or AlCl3 leads to a rapid increase in Fe-P
      nucleation rates, whereas low concentration MgCl2 inhibits goethite dissolution,
      this in turn influences Fe-P nucleation. Moreover, kinetic data analyses show
      that low concentrations of citrate caused an increase in the nucleation rate of
      Fe-P phases. However, at higher concentrations of citrate, nucleation
      acceleration was reversed with much longer induction times to form Fe-P nuclei.
      These in situ observations may improve the mechanistic understanding of processes
      resulting in phosphate immobilization by goethite-rich acid soils in the presence
      of various inorganic and organic additive molecules. 

PMID- 25763814
TI  - Monocarboxylation and intramolecular coupling of butenylated arenes via palladium
      catalyzed C-H activation process.
AB  - A novel and practical reaction for the direct intramolecular oxidative coupling
      of butenylated arenes is reported. With the catalysis of Pd(OAc)2, reactions of
      various butenylated arenes and carboxylic acids with Selectfluor reagent in CH3CN
      solution afforded the corresponding monocarboxylation/cyclization products in
      good yields under mild conditions. This research demonstrated an economic method
      with the synthesis of 2-tetralyl carboxylic esters, a valuable class of bioactive
      compounds. 

PMID- 25763813
TI  - Optimization of Recombinant Adeno-Associated Virus-Mediated Expression for Large
      Transgenes, Using a Synthetic Promoter and Tandem Array Enhancers.
AB  - The packaging capacity of recombinant adeno-associated viral (rAAV) vectors
      limits the size of the promoter that can be used to express the 4.43-kb cystic
      fibrosis transmembrane conductance regulator (CFTR) cDNA. To circumvent this
      limitation, we screened a set of 100-mer synthetic enhancer elements, composed of
      ten 10-bp repeats, for their ability to augment CFTR transgene expression from a
      short 83-bp synthetic promoter in the context of an rAAV vector designed for use
      in the cystic fibrosis (CF) ferret model. Our initial studies assessing
      transcriptional activity in monolayer (nonpolarized) cultures of human airway
      cell lines and primary ferret airway cells revealed that three of these synthetic
      enhancers (F1, F5, and F10) significantly promoted transcription of a luciferase
      transgene in the context of plasmid transfection. Further analysis in polarized
      cultures of human and ferret airway epithelia at an air-liquid interface (ALI),
      as well as in the ferret airway in vivo, demonstrated that the F5 enhancer
      produced the highest level of transgene expression in the context of an AAV
      vector. Furthermore, we demonstrated that increasing the size of the viral genome
      from 4.94 to 5.04 kb did not significantly affect particle yield of the vectors,
      but dramatically reduced the functionality of rAAV-CFTR vectors because of small
      terminal deletions that extended into the CFTR expression cassette of the 5.04-kb
      oversized genome. Because rAAV-CFTR vectors greater than 5 kb in size are
      dramatically impaired with respect to vector efficacy, we used a shortened ferret
      CFTR minigene with a 159-bp deletion in the R domain to construct an rAAV vector
      (AV2/2.F5tg83-fCFTRDeltaR). This vector yielded an ~17-fold increase in
      expression of CFTR and significantly improved Cl(-) currents in CF ALI cultures.
      Our study has identified a small enhancer/promoter combination that may have
      broad usefulness for rAAV-mediated CF gene therapy to the airway. 

PMID- 25763815
TI  - Association of systemic inflammation with epicardial fat and coronary artery
      calcification.
AB  - BACKGROUND: Increased epicardial fat volume (EFV) has been shown to be associated
      with coronary atherosclerosis. While it is postulated to be an independent risk
      factor, a possible mechanism is local or systemic inflammation. We analyzed the
      relationship between coronary atherosclerosis, quantified by coronary calcium in
      CT, epicardial fat volume and systemic inflammation. METHODS: Using non-enhanced
      dual-source CT, we quantified epicardial fat volume (EFV) and coronary artery
      calcium (CAC) in 391 patients who underwent coronary computed tomography for
      suspected coronary artery disease. In addition to traditional risk factors, serum
      markers of systemic inflammation were measured (IL-1alpha, IL-2, IL-4, IL-6, IL
      7, IL-8, IL-10,IL-12, IL-13, IL-15, IL-17, IFN-gamma, TNF-alpha, hs-CRP, GM-CS, G
      CSF, MCP-1, MIP-1, Eotaxin and IP-10). In 94 patients follow-up data were
      obtained after 1.9 +/- 0.5 years. RESULTS: The 391 patients had a mean age of 60
      +/- 10 years, and 69 % were males. Mean EFV was 116 +/- 50 mL. Median CAC was 12
      (IQR 0; 152). CAC and EFV showed a significant correlation (rho = 0.37; P <
      0.001). EFV and CAC were significantly correlated with the traditional risk
      factors like age, male gender, diabetes, smoking and hypertension. With regard to
      biomarkers, CAC was significantly associated (negatively) to G-CSF and IL-13. EFV
      (median binned) was significantly associated (positively) with IP-10 (P = 0.002)
      and MCP-1 (rho = 0.037). In follow-up, EFV showed a mean annualized progression
      of 6 mL (IQR 3; 9) (P < 0.001); CAC progressed by a mean of six Agatston Units
      (IQR 0; 30). The progression of CAC was significantly correlated with the extent
      of EFV (P < 0.001) while there was no significant correlation between progression
      of EFV or CAC with systemic inflammation markers. CONCLUSION: Epicardial fat
      volume and the baseline extent as well as progression of coronary atherosclerosis
      measured by the calcium score-are significantly correlated. While both baseline
      EFV and CAC displayed significant correlations with systemic inflammation
      markers, biomarkers were not predictive of the progression of CAC or EFV.

PMID- 25763816
TI  - Predicting epidemic risk from past temporal contact data.
AB  - Understanding how epidemics spread in a system is a crucial step to prevent and
      control outbreaks, with broad implications on the system's functioning, health,
      and associated costs. This can be achieved by identifying the elements at higher
      risk of infection and implementing targeted surveillance and control measures.
      One important ingredient to consider is the pattern of disease-transmission
      contacts among the elements, however lack of data or delays in providing updated
      records may hinder its use, especially for time-varying patterns. Here we explore
      to what extent it is possible to use past temporal data of a system's pattern of
      contacts to predict the risk of infection of its elements during an emerging
      outbreak, in absence of updated data. We focus on two real-world temporal
      systems; a livestock displacements trade network among animal holdings, and a
      network of sexual encounters in high-end prostitution. We define the node's
      loyalty as a local measure of its tendency to maintain contacts with the same
      elements over time, and uncover important non-trivial correlations with the
      node's epidemic risk. We show that a risk assessment analysis incorporating this
      knowledge and based on past structural and temporal pattern properties provides
      accurate predictions for both systems. Its generalizability is tested by
      introducing a theoretical model for generating synthetic temporal networks. High
      accuracy of our predictions is recovered across different settings, while the
      amount of possible predictions is system-specific. The proposed method can
      provide crucial information for the setup of targeted intervention strategies. 

PMID- 25763817
TI  - On the role of protein disulfide isomerase in the retrograde cell transport of
      secreted phospholipases A2.
AB  - Following the finding that ammodytoxin (Atx), a neurotoxic secreted phospholipase
      A2 (sPLA2) in snake venom, binds specifically to protein disulfide isomerase
      (PDI) in vitro we show that these proteins also interact in living rat PC12 cells
      that are able to internalize this group IIA (GIIA) sPLA2. Atx and PDI co-localize
      in both differentiated and non-differentiated PC12 cells, as shown by
      fluorescence microscopy. Based on a model of the complex between Atx and yeast
      PDI (yPDI), a three-dimensional model of the complex between Atx and human PDI
      (hPDI) was constructed. The Atx binding site on hPDI is situated between domains
      b and b'. Atx interacts hPDI with an extensive area on its interfacial binding
      surface. The mammalian GIB, GIIA, GV and GX sPLA2s have the same fold as Atx. The
      first three sPLA2s have been detected intracellularly but not the last one. The
      models of their complexes with hPDI were constructed by replacement of Atx with
      the respective mammalian sPLA2 in the Atx-hPDI complex and molecular docking of
      the structures. According to the generated models, mammalian GIB, GIIA and GV
      sPLA2s form complexes with hPDI very similar to that with Atx. The contact area
      between GX sPLA2 and hPDI is however different from that of the other sPLA2s.
      Heterologous competition of Atx binding to hPDI with GV and GX sPLA2s confirmed
      the model-based expectation that GV sPLA2 was a more effective inhibitor than GX
      sPLA2, thus validating our model. The results suggest a role of hPDI in the
      (patho)physiology of some snake venom and mammalian sPLA2s by assisting the
      retrograde transport of these molecules from the cell surface. The sPLA2-hPDI
      model constitutes a valuable tool to facilitate further insights into this
      process and into the (patho)physiology of sPLA2s in relation to their action
      intracellularly. 

PMID- 25763818
TI  - TRIM26 negatively regulates interferon-beta production and antiviral response
      through polyubiquitination and degradation of nuclear IRF3.
AB  - Virus infection leads to the activation of transcription factor IRF3 and
      subsequent production of type I inteferons, which induce the transcription of
      various antiviral genes called interferon stimulated genes (ISGs) to eliminate
      viral infection. IRF3 activation requires phosphorylation, dimerization and
      nuclear translocation. However, the mechanisms for the termination of IRF3
      activation in nucleus are elusive. Here we report the identification of TRIM26 to
      negatively regulate IFN-beta production and antiviral response by targeting
      nuclear IRF3. TRIM26 bound to IRF3 and promoted its K48-linked polyubiquitination
      and degradation in nucleus. TRIM26 degraded WT IRF3 and the constitutive active
      mutant IRF3 5D, but not the phosphorylation deficient mutant IRF3 5A.
      Furthermore, IRF3 mutant in the Nuclear Localization Signal (NLS), which could
      not move into nucleus, was not degraded by TRIM26. Importantly, virus infection
      promoted TRIM26 nuclear translocation, which was required for IRF3 degradation.
      As a consequence, TRIM26 attenuated IFN-beta promoter activation and IFN-beta
      production downstream of TLR3/4, RLR and DNA sensing pathways. TRIM26 transgenic
      mice showed much less IRF3 activation and IFN-beta production, while increased
      virus replication. Our findings delineate a novel mechanism for the termination
      of IRF3 activation in nucleus through TRIM26-mediated IRF3 ubiquitination and
      degradation. 

PMID- 25763819
TI  - Genetic background effects on disease onset and lifespan of the mutant dynactin
      p150Glued mouse model of motor neuron disease.
AB  - Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease primarily
      affecting motor neurons in the central nervous system. Although most cases of ALS
      are sporadic, about 5-10% of cases are familial (FALS) with approximately 20% of
      FALS caused by mutations in the Cu/Zn superoxide dismutase (SOD1) gene. We have
      reported that hSOD1-G93A transgenic mice modeling this disease show a more severe
      phenotype when the transgene is bred on a pure SJL background and a milder
      phenotype when bred on a pure B6 background and that these phenotype differences
      link to a region on mouse Chromosome 17.To examine whether other models of motor
      neuron degeneration are affected by genetic background, we bred the mutant human
      dynactin p150Glued (G59S-hDCTN1) transgene onto inbred SJL and B6 congenic lines.
      This model is based on an autosomal dominant lower motor neuron disease in humans
      linked to a mutation in the p150Glued subunit of the dynactin complex. As seen in
      hSOD1-G93A mice, we observed a more severe phenotype with earlier disease onset
      (p<0.001) and decreased survival (p<0.00001) when the G59S-hDCTN1 transgene was
      bred onto the SJL background and delayed onset (p<0.0001) with increased survival
      (p<0.00001) when bred onto the B6 background. Furthermore, B6 mice with an SJL
      derived chromosome 17 interval previously shown to delay disease onset in hSOD1
      G93A mice also showed delays onset in G59S-hDCTN1 mice suggesting that at least
      some genetic modifiers are shared. We have shown that genetic background
      influences phenotype in G59S-hDCTN1 mice, in part through a region of chromosome
      17 similar to the G93-hSOD1 ALS mouse model. These results support the presence
      of genetic modifiers in both these models some of which may be shared.
      Identification of these modifiers will highlight intracellular pathways involved
      in motor neuron disease and provide new therapeutic targets that may be
      applicable to motor neuron degeneration. 

PMID- 25763820
TI  - Biodiversity of Jinggangshan Mountain: the importance of topography and
      geographical location in supporting higher biodiversity.
AB  - Diversity is mainly determined by climate and environment. In addition,
      topography is a complex factor, and the relationship between topography and
      biodiversity is still poorly understood. To understand the role of topography,
      i.e., altitude and slope, in biodiversity, we selected Jinggangshan Mountain
      (JGM), an area with unique topography, as the study area. We surveyed plant and
      animal species richness of JGM and compared the biodiversity and the main
      geographic characteristics of JGM with the adjacent 4 mountains. Gleason's
      richness index was calculated to assess the diversity of species. In total, 2958
      spermatophyte species, 418 bryophyte species, 355 pteridophyte species and 493
      species of vertebrate animals were recorded in this survey. In general, the JGM
      biodiversity was higher than that of the adjacent mountains. Regarding
      topographic characteristics, 77% of JGM's area was in the mid-altitude region and
      approximately 40% of JGM's area was in the 10 degrees -20 degrees  slope range,
      which may support more vegetation types in JGM area and make it a biodiversity
      hotspot. It should be noted that although the impact of topography on
      biodiversity was substantial, climate is still a more general factor driving the
      formation and maintenance of higher biodiversity. Topographic conditions can
      create microclimates, and both climatic and topographic conditions contribute to
      the formation of high biodiversity in JGM. 

PMID- 25763822
TI  - A permutation test for oligoset DNA pooling studies.
AB  - Case-control association studies often suffer from population stratification
      bias. A previous triple combination strategy of stratum matching, genomic
      controlling, and multiple DNA pooling can correct the bias and save genotyping
      cost. However the method requires researchers to prepare a multitude of DNA pools
      more than 30 case-control pooling sets in total (polyset). In this paper, the
      authors propose a permutation test for oligoset DNA pooling studies. Monte-Carlo
      simulations show that the proposed test has a type I error rate under control and
      a power comparable to that of individual genotyping. For a researcher on a tight
      budget, oligoset DNA pooling is a viable option. 

PMID- 25763821
TI  - Elimination of cancer stem-like cells and potentiation of temozolomide
      sensitivity by Honokiol in glioblastoma multiforme cells.
AB  - Glioblastoma multiforme (GBM) is the most common adult malignant glioma with poor
      prognosis due to the resistance to radiotherapy and chemotherapy, which might be
      critically involved in the repopulation of cancer stem cells (CSCs) after
      treatment. We had investigated the characteristics of cancer stem-like side
      population (SP) cells sorted from GBM cells, and studied the effect of Honokiol
      targeting on CSCs. GBM8401 SP cells possessed the stem cell markers, such as
      nestin, CD133 and Oct4, and the expressions of self-renewal related stemness
      genes, such as SMO, Notch3 and IHH (Indian Hedgehog). Honokiol inhibited the
      proliferation of both GBM8401 parental cells and SP cells in a dose-dependent
      manner, the IC50 were 5.3+/-0.72 and 11+/-1.1 MUM, respectively. The proportions
      of SP in GBM8401 cells were diminished by Honokiol from 1.5+/-0.22% down to 0.3+/
      0.02% and 0.2+/-0.01% at doses of 2.5 MUM and 5 MUM, respectively. The SP cells
      appeared to have higher expression of O6-methylguanine-DNA methyltransferase
      (MGMT) and be more resistant to Temozolomide (TMZ). The resistance to TMZ could
      be only slightly reversed by MGMT inhibitor O6-benzylguanine (O6-BG), but
      markedly further enhanced by Honokiol addition. Such significant enhancement was
      accompanied with the higher induction of apoptosis, greater down-regulation of
      Notch3 as well as its downstream Hes1 expressions in SP cells. Our data indicate
      that Honokiol might have clinical benefits for the GBM patients who are
      refractory to TMZ treatment. 

PMID- 25763823
TI  - A mouse model of L-2-hydroxyglutaric aciduria, a disorder of metabolite repair.
AB  - The purpose of the present work was to progress in our understanding of the
      pathophysiology of L-2-hydroxyglutaric aciduria, due to a defect in L-2
      hydroxyglutarate dehydrogenase, by creating and studying a mouse model of this
      disease. L-2-hydroxyglutarate dehydrogenase-deficient mice (l2hgdh-/-)
      accumulated L-2-hydroxyglutarate in tissues, most particularly in brain and
      testis, where the concentration reached ~ 3.5 MUmol/g. Male mice showed a 30%
      higher excretion of L-2-hydroxyglutarate compared to female mice, supporting that
      this dicarboxylic acid is partially made in males by lactate dehydrogenase C, a
      poorly specific form of this enzyme exclusively expressed in testes. Involvement
      of mitochondrial malate dehydrogenase in the formation of L-2-hydroxyglutarate
      was supported by the commensurate decrease in the formation of this dicarboxylic
      acid when down-regulating this enzyme in mouse l2hgdh-/- embryonic fibroblasts.
      The concentration of lysine and arginine was markedly increased in the brain of
      l2hgdh-/- adult mice. Saccharopine was depleted and glutamine was decreased by ~
      40%. Lysine-alpha-ketoglutarate reductase, which converts lysine to saccharopine,
      was inhibited by L-2-hydroxyglutarate with a Ki of ~ 0.8 mM. As low but
      significant activities of the bifunctional enzyme lysine-alpha-ketoglutarate
      reductase/saccharopine dehydrogenase were found in brain, these findings suggest
      that the classical lysine degradation pathway also operates in brain and is
      inhibited by the high concentrations of L-2-hydroxyglutarate found in l2hgdh-/-
      mice. Pathological analysis of the brain showed significant spongiosis. The
      vacuolar lesions mostly affected oligodendrocytes and myelin sheats, as in other
      dicarboxylic acidurias, suggesting that the pathophysiology of this model of
      leukodystrophy may involve irreversible pumping of a dicarboxylate in
      oligodendrocytes. Neurobehavioral testing indicated that the mice mostly suffered
      from a deficit in learning capacity. In conclusion, the findings support the
      concept that L-2-hydroxyglutaric aciduria is a disorder of metabolite repair. The
      accumulation of L-2-hydroxyglutarate exerts toxic effects through various means
      including enzyme inhibition and glial cell swelling. 

PMID- 25763824
TI  - No effect of an elevated miR-30b level in mouse milk on its level in pup tissues.
AB  - Recent reports have shown that ingested microRNAs may be transferred to blood,
      accumulate in tissues and exert canonical regulation on endogenous transcripts.
      In spite of several attempts to replicate these findings, they have not been
      confirmed and several questions remain. By using a transgenic mouse model
      presenting a high level of miR-30b in milk, the horizontal delivery of this
      microRNA via oral ingestion was studied in pups. Our findings demonstrated that,
      although very high levels of miR-30b were found in milk and in stomach contents
      of the pups, we did not detect an increase in miR-30b in tissues of pups fed by
      transgenic females compared to pups fed by wild-type females. 

PMID- 25763825
TI  - Understanding empathy: why phenomenology and hermeneutics can help medical
      education and practice.
AB  - This article offers a critique and reformulation of the concept of empathy as it
      is currently used in the context of medicine and medical care. My argument is
      three pronged. First, that the instrumentalised notion of empathy that has been
      common within medicine erases the term's rich epistemological history as a
      special form of understanding, even a vehicle of social inquiry, and has instead
      substituted an account unsustainably structured according to the polarisations of
      modernity (subject/object, active/passive, knower/known, mind/body,
      doctor/patient). I suggest that understanding empathy by examining its origins
      within the phenomenological tradition, as a mode of intersubjective
      understanding, offers a different and profitable approach. Secondly, I argue that
      the appropriation of empathy in medicine means that, ironically, empathy can
      function as a technique of pastoral power, in which virtue, knowledge and
      authority remain with the doctor (Mayes in Bioeth Inq 6:483-493, doi:
      10.1007/s11673-009-9195-9 , 2009). And thirdly, empathy is in danger of being
      resourced as a substitute for equity and funding within health systems. I
      conclude however with hope for the productive possibilities for empathy. 

PMID- 25763826
TI  - Optimizing clinical trial design for multiple system atrophy: lessons from the
      rifampicin study.
AB  - Multiple system atrophy (MSA) is a fatal neurodegenerative disorder characterized
      by autonomic failure and parkinsonism/ataxia; no treatment exists to slow disease
      progression. A number of factors have prevented or compromised trials targeting
      disease modification. A major hurdle has been uncertainty about the number of
      patients needed to achieve adequate power. Information based on natural history
      studies suggested such numbers to be so large that only international multi
      center models seemed feasible. When designing the rifampicin trial in MSA we
      sought to identify and apply strategies that would improve power and reduce the
      number needed to treat to allow for an oligocenter approach. Strategies included:
      (1) inclusion/exclusion criteria designed to enroll patients with relatively
      early, actively progressing disease; (2) minimizing dropouts; (3) pre-defined
      interim analysis; and (4) approaches to reduce scoring variability. The model
      allowed for the number needed to treat to be only 50 patients per treatment arm.
      Ten selected sites managed to reach the recruitment goal within 12 months. The
      dropout rate was less than 10%, and the goal of enrolling patients with actively
      progressing disease was accomplished as reflected by the progression rate in the
      placebo group. Data from this unfortunately negative trial can now be effectively
      used to more realistically power future trials. A number of ways to further
      improve trial design and feasibility have been identified and include rigorous
      site selection and training, designated primary site investigators, improved
      error trapping, early site visits, remedial training, and future biomarkers for
      earlier diagnosis and tracking of disease progression.

PMID- 25763827
TI  - Cost-effectiveness analysis of simeprevir in combination with peginterferon and
      ribavirin for treatment-naive chronic hepatitis C genotype 1 patients in Japan.
AB  - AIM: Simeprevir (SMV), a protease inhibitor, recently became available for the
      treatment of chronic hepatitis C (HCV) genotype 1 patients in Japan. The
      introduction of triple therapy using SMV in combination with peginterferon and
      ribavirin (PR) significantly improves the cure rate. The aim was to assess the
      cost-effectiveness of SMV with PR (SMV/PR) compared to telaprevir with PR
      (TVR/PR), PR alone, or no treatment in treatment-naive patients in Japan.
      METHODS: A Markov model was developed to reflect the natural disease progression
      of HCV and to estimate the average life years and lifetime healthcare costs per
      patient. Sustained virologic response rates were obtained from a network meta
      analysis including randomized clinical trials conducted in Japan. Patient
      baseline characteristics, HCV progression rates, mortality, medical resource
      utilization, and unit costs were obtained from Japanese sources. Outcomes were
      reported as incremental cost-effectiveness ratios as well as incremental cost and
      life years. Various sensitivity analyses were conducted to assess the uncertainty
      around model outcomes. RESULTS: SMV/PR was estimated to be a cost-effective
      treatment option as more life years were gained by 0.235 and 0.873 years at a
      reduced cost by Y263,037 and Y776,900 compared to TVR/PR and PR alone,
      respectively. The results were robust to sensitivity analyses, in particular in
      the comparison of SMV/PR with PR alone. The multivariate probabilistic
      sensitivity analyses showed that the probability of SMV/PR being cost-effective
      was relatively constant at ~87% at any willingness to pay. CONCLUSIONS: SMV/PR is
      estimated to be the most cost-effective treatment strategy for treatment-naive
      HCV genotype 1 patients in Japan.

PMID- 25763828
TI  - Combined Use of MR Fat Quantification and MR Elastography in Living Liver Donors:
      Can It Reduce the Need for Preoperative Liver Biopsy?
AB  - PURPOSE: To evaluate the diagnostic performance of magnetic resonance (MR) fat
      quantification and MR elastography for the assessment of hepatic steatosis and
      fibrosis in living liver donor candidates. MATERIALS AND METHODS: This
      retrospective study was approved by the institutional review board, and the
      requirement of informed consent was waived. Donors who underwent MR fat
      quantification and MR elastography at 1.5 T, followed by liver biopsy, were
      chronologically grouped into test and validation groups. In the test group (n =
      362), MR fat fraction and liver stiffness were compared among donors with normal
      parenchyma (n = 244), simple steatosis (n = 71), steatosis with inflammatory
      activity (n = 21), nonalcoholic steatohepatitis (n = 17), and fibrosis (n = 9).
      Diagnostic performance of the two techniques was assessed by using receiver
      operating characteristic curve analysis for the detection of substantial
      steatosis (macrovesicular fat >= 10%) or fibrosis (>=F1) and was tested in a
      validation group (n = 34). RESULTS: In the test group, donors with steatosis
      showed significantly higher fat fraction than donors without steatosis (P <
      .0001), and donors with fibrosis and nonalcoholic steatohepatitis showed
      significantly higher liver stiffness values than donors without fibrosis (P <
      .0001). Areas under the curve were 0.93 (cutoff value > 5.8%) for MR fat
      quantification and 0.85 (cutoff value > 1.94 kPa) for MR elastography. By using
      those values, the combination of the two techniques could be used to detect
      substantial steatosis or fibrosis with 100% sensitivity (12 of 12 patients, 95%
      confidence interval: 73.4%, 100%) and 100% negative predictive value (15 of 15
      patients, 95% confidence interval: 78.0%, 100%) in the validation group.
      CONCLUSION: A combination of MR fat quantification and MR elastography can
      provide sufficient sensitivity to detect substantial steatosis or fibrosis (>=F1)
      in liver donor candidates.

PMID- 25763830
TI  - Evaluation of the Effect of Cumulative Operator Experience on Hepatocellular
      Carcinoma Recurrence after Primary Treatment with Radiofrequency Ablation.
AB  - PURPOSE: To investigate the association between cumulative operator volume and
      the risk of hepatocellular carcinoma (HCC) recurrence after potentially curative
      radiofrequency ablation (RFA). MATERIALS AND METHODS: This study was approved by
      the Research Ethics Committee. By using the Taiwan National Health Insurance
      Research Database, 52 096 patients with HCC were identified between July 1, 2004,
      and December 31, 2011. In total, 2827 patients were selected who underwent
      potentially curative RFA for newly diagnosed HCC. These patients were grouped
      into quintiles according to the cumulative operator volumes. Patients in the
      lowest or the highest quintiles were 1:1 matched according to their propensity
      scores. Finally, two separate groups, each containing 406 patients, were
      recruited in the high- and low-volume groups (cumulative operator volume of >=79
      cases and <=10 cases, respectively). Cumulative incidences of and hazard ratios
      for HCC recurrence were analyzed after adjusting for competing mortality.
      RESULTS: The HCC recurrence rate of the high-volume group was significantly lower
      than that of the low-volume group (high-volume group 5-year recurrence rate of
      65.8%, 95% confidence interval [CI]: 59.5%, 72.1%; low-volume group 5-year
      recurrence rate of 71.4%, 95% CI: 66.2%, 76.5%; P < .05). In modified Cox
      regression analysis, the highest cumulative operator volume was independently
      associated with a decreased risk of HCC recurrence (hazard ratio, 0.80; 95% CI:
      0.67, 0.97; P < .05). Multivariable stratified analyses verified the association
      between the highest cumulative operator volume and decreased HCC recurrence in
      almost all subgroups. CONCLUSION: The risk of HCC recurrence could be
      significantly decreased by experienced RFA operators. Further studies based on
      cumulative operator volume may be helpful in improving the quality of RFA for
      HCC.

PMID- 25763829
TI  - Gadolinium Chelate Contrast Material in Pregnancy: Fetal Biodistribution in the
      Nonhuman Primate.
AB  - PURPOSE: To determine the extent to which gadolinium chelate is found in nonhuman
      primate fetal tissues and amniotic fluid at 19-45 hours after intravenous
      injection of a weight-appropriate maternal dose of the contrast agent
      gadoteridol. MATERIALS AND METHODS: Gravid Japanese macaques (n = 14) were
      maintained as approved by the institutional animal care and utilization
      committee. In the 3rd trimester of pregnancy, the macaques were injected with
      gadoteridol (0.1 mmol per kilogram of maternal weight). Fetuses were delivered by
      means of cesarean section within 24 hours of maternal injection (range, 19-21
      hours; n = 11) or 45 hours after injection (n = 3). Gadolinium chelate levels in
      the placenta, fetal tissues, and amniotic fluid were obtained by using
      inductively coupled plasma mass spectrometry. The Wilcoxon rank sum test was used
      for quantitative comparisons. RESULTS: Gadoteridol was present in the
      fetoplacental circulation at much lower quantities than in the mother. At both
      time points, the distribution of gadolinium chelate in the fetus was comparable
      to that expected in an adult. The highest concentration of the injected dose (ID)
      was found in the fetal kidney (0.0161% ID per gram in the 19-21-hour group). The
      majority of the in utero gadolinium chelate was found in the amniotic fluid and
      the placenta (mean, 0.1361% ID per organ +/- 0.076 [standard deviation] and
      0.0939% ID per organ +/- 0.0494, respectively). Data acquired 45 hours after
      injection showed a significant decrease in the gadolinium chelate concentration
      in amniotic fluid compared with that in the 19-21-hour group (from 0.0017% to
      0.0007% ID per gram; P = .01). CONCLUSION: Amounts of gadolinium chelate in the
      fetal tissues and amniotic fluid were minimal compared with the maternal ID. This
      may impact future clinical studies on the safety of gadolinium contrast agent use
      in pregnancy.

PMID- 25763831
TI  - Endoscopic mucosal resection of laterally spreading lesions involving the
      ileocecal valve: technique, risk factors for failure, and outcomes.
AB  - BACKGROUND AND STUDY AIMS: Endoscopic mucosal resection (EMR) of laterally
      spreading lesions (LSLs) involving the ileocecal valve (ICV) is technically
      demanding. Conventionally, these lesions are considered too challenging for
      endoscopic therapy and are primarily managed surgically. The aims of the study
      were to describe effectiveness, safety, and outcomes following EMR of LSLs at the
      ICV. PATIENTS AND METHODS: This was a single-center, prospective, observational,
      cohort study performed at an academic, tertiary referral center. Patients
      undergoing EMR for LSLs >= 20 mm involving the ICV were recruited over a 5-year
      period. Standard or cap-assisted colonoscopy with inject-and-resect EMR technique
      was performed with standardized post-EMR management. Procedural success, safety,
      and outcomes compared with non-ICV LSLs managed during the same period were
      analyzed. RESULTS: A total of 53 patients with ICV LSLs were referred for EMR
      (median age 69 years; median lesion size 35.0 mm; 52.8 % females). Six patients
      went directly to surgery because of an endoscopic diagnosis of malignancy (n = 2)
      or technical failure of EMR (n = 4). EMR achieved complete adenoma clearance in
      44 out of 47 attempted (93.6 %). Surgery was ultimately avoided in 43/53 (81.1
      %). Complications included bleeding in 6.4 %. There were no perforations or
      strictures. Early adenoma recurrence was detected in 7/40 patients (17.5 %), and
      1/22 (4.5 %) had late recurrence. All were successfully managed endoscopically.
      Factors associated with failure of ICV EMR were ileal infiltration and
      involvement of both ICV lips. CONCLUSIONS: In the majority of cases, LSL
      involving the ICV can be effectively treated by EMR on an outpatient basis. In
      specialized centers, complications are infrequent, and  > 80 % of patients
      ultimately avoid surgery. Trial registered at ClinicalTrials.gov (NCT01368289).

PMID- 25763832
TI  - Cystic pancreatic neuroendocrine tumors: outcomes of preoperative endosonography
      guided fine needle aspiration, and recurrence during long-term follow-up.
AB  - BACKGROUND AND STUDY AIMS: The role of endoscopic ultrasound-guided fine needle
      aspiration (EUS-FNA) in the diagnosis and management of cystic pancreatic
      neuroendocrine tumors (PNETs) is unclear. We aimed to compare
      clinical/endosonographic characteristics of cystic with solid PNETs, determine
      diagnostic accuracy of preoperative EUS-FNA, and evaluate recurrence rates after
      resection. PATIENTS AND METHODS: All patients with cystic or solid PNET confirmed
      by EUS-FNA between 2000 and 2014 were identified. A matched case-control study
      compared 50 consecutive patients with cystic PNETs with 50 consecutive patients
      with solid PNETs, matched by gender and age at diagnosis of index cystic PNET. We
      compared clinical/endosonographic characteristics, assessed diagnostic accuracy
      of preoperative EUS-FNA for identifying malignancy, and analyzed tumor-free
      survival of patients with cystic and solid PNETs. RESULTS: Cystic PNETs tended to
      be larger than solid PNETs (mean 26.8 vs. 20.1 mm, P = 0.05), more frequently
      nonfunctional (96 % vs. 80 %, P = 0.03), and less frequently associated with
      multiple endocrine neoplasia type 1 (10 % vs. 28 %, P = 0.04). With surgical
      pathology as reference standard, EUS-FNA accuracies for malignancy of cystic and
      solid PNETs were 89.3 % and 90 %, respectively; cystic PNETs were less associated
      with metastatic adenopathy (22 % vs. 42 %, P = 0.03) and liver metastasis (0 %
      vs. 26 %, P < 0.001). Cystic fluid analysis (n = 13), showed benign cystic PNETs
      had low carcinoembryonic antigen (CEA), Ki-67 <= 2 %, and no loss of
      heterozygosity. Patients with cystic and solid PNETs had similar recurrence risk
      up to 5 years after complete resection. CONCLUSIONS: Cystic PNETs have distinct
      clinical and EUS characteristics, but were associated with less aggressive
      biological behavior compared with solid PNETs. EUS-FNA is accurate for
      determining malignant potential on preoperative evaluation. Despite complete
      resection, recurrence is observed up to 5 years following surgery.

PMID- 25763833
TI  - Endoscopic full-thickness resection in the colorectum with a novel over-the-scope
      device: first experience.
AB  - BACKGROUND AND STUDY AIMS: Endoscopic full-thickness resection (EFTR) in the
      lower gastrointestinal tract may be a valuable therapeutic and diagnostic
      approach for a variety of indications. Although feasibility of EFTR has been
      demonstrated, there is a lack of safe and effective endoscopic devices for
      routine use. The aim of this study was to investigate the efficacy and safety of
      a novel over-the-scope device for colorectal EFTR. PATIENTS AND METHODS: Between
      July 2012 and July 2014, 25 patients underwent EFTR at two tertiary referral
      centers. All resections were performed using the full-thickness resection device
      (FTRD; Ovesco Endoscopy, Tubingen, Germany). Data were collected retrospectively.
      RESULTS: Indications for EFTR were: recurrent or incompletely resected adenoma
      with nonlifting sign (n = 11), untreated adenoma and nonlifting sign (n = 2),
      adenoma involving the appendix (n = 5), flat adenoma in a patient with
      coagulopathy (n = 1), diagnostic re-resection after incomplete resection of a T1
      carcinoma (n = 2), adenoma involving a diverticulum (n = 1), submucosal tumor (n
      = 2), and diagnostic resection in a patient with suspected Hirschsprung's disease
      (n = 1). In one patient, the lesion could not be reached because of a sigmoid
      stenosis. In the other patients, resection of the lesion was macroscopically
      complete and en bloc in 20/24 patients (83.3 %). The mean diameter of the
      resection specimen was 24 mm (range 12 - 40 mm). The R0 resection rate was 75.0 %
      (18/24), and full-thickness resection was histologically confirmed in 87.5 %. No
      perforations or major bleeding were observed during or after resection. Two
      patients developed postpolypectomy syndrome, which was managed with antibiotic
      therapy. CONCLUSIONS: Full-thickness resection in the lower gastrointestinal
      tract with the novel FTRD was feasible and effective. Prospective studies are
      needed to further evaluate the device and technique.

PMID- 25763834
TI  - Live imaging of axonal transport in Drosophila pupal brain explants.
AB  - Axonal transport is essential for the initial growth, maintenance and synaptic
      plasticity of axons, and altered axonal transport has been observed in different
      models of neurodegenerative pathologies. Dissecting the mechanisms underlying
      axonal transport in developing or degenerating brains requires dynamic imaging of
      axonal cargo movement in living samples. Whereas methods exist to image axonal
      transport in Drosophila larval neurons, they are not suitable to follow this
      process during metamorphosis, when brains undergo extensive remodeling. Here we
      present a simple method that enables confocal imaging of both fast and slow
      axonal transport in Drosophila pupal brain explants. We describe how to prepare
      chambers adapted for live imaging, how to maintain brain explants under
      physiological conditions and how to monitor and quantitatively analyze the
      movement of fluorescently labeled cargoes. This protocol requires minimal
      equipment and is ideally suited for experiments that combine genetics,
      optogenetics and pharmacological approaches. The brains can be prepared for image
      acquisition in 1.5 h, and the protocol can be performed easily in any fly
      laboratory. 

PMID- 25763835
TI  - A two-component 'double-click' approach to peptide stapling.
AB  - Peptide cyclization is a useful strategy for the stabilization of short flexible
      peptides into well-defined bioactive conformations, thereby enhancing their
      ability to interact with proteins and other important biomolecules. We present an
      optimized procedure for the stabilization of linear diazido peptides in an alpha
      helical conformation upon reaction with dialkynyl linkers under Cu(I) catalysis.
      As this procedure generates side chain-cyclized peptides bearing a bis-triazole
      linkage, it is referred to as 'double-click' stapling. Double-click stapling can
      enhance the binding affinity, proteolytic stability and cellular activity of a
      peptide inhibitor. A distinguishing feature of double-click stapling is the
      efficiency with which peptides bearing different staple linkages can be
      synthesized, thus allowing for modular control over peptide bioactivity. This
      protocol describes the double-click reaction between a 1,3-dialkynylbenzene
      linker and peptides that contain azidoornithine. Subsequent peptide purification
      and confirmation steps are also described. The entire double-click stapling
      protocol can be completed in ~48 h, including two overnight lyophilization steps.

PMID- 25763836
TI  - Transplanted tumor growth and the incidence of T-lymphocyte populations in the
      spleen of newcastle virus-treated mice.
AB  - C3Hf/HZgr mice were transplanted with SCCVII carcinoma cells and treated with
      Newcastle disease virus (NDV). The treatment slows down the growth of
      transplanted tumor. Furthermore, by using specific monoclonal antibodies, the
      frequencies of CD4+, CD8+, and CD4+CD25+ T lymphocytes were determined in the
      spleen of tumorous mice at particular times following tumor transplantation
      and/or NDV application. The incidence of lymphocytes CD4+ and CD8+ decreased and
      of CD4+CD25+ increased in the spleen of mice during the time following tumor
      transplantation. However, the frequency of regulatory CD4+CD25+ T lymphocytes in
      the spleen is very low, while CD4+ and CD8+ increased to normal level following
      intraperitoneal (i.p.) NDV injection in tumor-bearing mice. Thus, besides
      directly destroying transplanted tumor, NDV seems to be involved against growing
      tumor by reducing the frequency of regulatory T lymphocytes maintaining the
      frequency of CD4+ and CD8+ T lymphocytes within the control values pointing to
      its role in immunomodulation. 

PMID- 25763837
TI  - Biofilm-forming bacteria and quality of life improvement after sinus surgery.
AB  - BACKGROUND: It remains unclear how much chronic rhinosinusitis (CRS) patients
      with bacterial biofilms can benefit from functional endoscopic sinus surgery
      (FESS). We aimed to evaluate whether biofilm-forming bacteria was associated with
      quality of life (QOL) improvement after FESS. METHODS: This retrospective cohort
      study included adult CRS patients who underwent FESS from 2008 to 2011. Sinus
      samples were taken to evaluate for biofilm-formation in vitro using a modified
      Calgary Biofilm Detection Assay. QOL was measured before FESS, and 1-month, 3
      month, and 6-month after FESS using 22-item Sino-Nasal Outcome Test (SNOT-22)
      scores. Patients' characteristics and medications were collected. Clinical
      significant QOL change was defined as a difference of at least 0.5 standard
      deviation (SD) of baseline SNOT-22 score in the reference group. RESULTS: A total
      of 156 patients had complete data, and 15% had biofilm-forming bacteria (n = 24).
      Patients with biofilm-forming bacteria had significantly worse preoperative SNOT
      22 scores compared to patients without biofilm-forming bacteria (48 +/- 20 vs 38
      +/- 23, p = 0.048). Both groups had clinically significant QOL improvement after
      FESS, and the differences in their 1-month (23 +/- 19 vs 17 +/- 20) and 3-month
      (27 +/- 18 vs 18 +/- 19) post-FESS SNOT-22 scores were not significant. However,
      patients with biofilm-forming bacteria demonstrated significantly less QOL
      improvement than patients without biofilm-forming bacteria from pre-FESS to 6
      month post-FESS visits after adjusting for clinical factors (35 +/- 25 vs 14 +/-
      15; beta-coefficient = 0.71; 95% confidence interval [CI], 0.13 to 1.28; p =
      0.016). CONCLUSION: CRS patients with biofilm-forming bacteria demonstrated
      clinically significant QOL improvement following FESS, but the degree of
      improvement was decreased overtime and became significantly worse than patients
      without biofilm-forming bacteria by 6-month follow-up. This QOL worsening was
      independent of other risk factors for CRS.

PMID- 25763838
TI  - VORFFIP-driven dock: V-D2OCK, a fast and accurate protein docking strategy.
AB  - The experimental determination of the structure of protein complexes cannot keep
      pace with the generation of interactomic data, hence resulting in an ever
      expanding gap. As the structural details of protein complexes are central to a
      full understanding of the function and dynamics of the cell machinery,
      alternative strategies are needed to circumvent the bottleneck in structure
      determination. Computational protein docking is a valid and valuable approach to
      model the structure of protein complexes. In this work, we describe a novel
      computational strategy to predict the structure of protein complexes based on
      data-driven docking: VORFFIP-driven dock (V-D2OCK). This new approach makes use
      of our newly described method to predict functional sites in protein structures,
      VORFFIP, to define the region to be sampled during docking and structural
      clustering to reduce the number of models to be examined by users. V-D2OCK has
      been benchmarked using a validated and diverse set of protein complexes and
      compared to a state-of-art docking method. The speed and accuracy compared to
      contemporary tools justifies the potential use of VD2OCK for high-throughput,
      genome-wide, protein docking. Finally, we have developed a web interface that
      allows users to browser and visualize V-D2OCK predictions from the convenience of
      their web-browsers. 

PMID- 25763839
TI  - Quality measures for gene expression biclusters.
AB  - An noticeable number of biclustering approaches have been proposed proposed for
      the study of gene expression data, especially for discovering functionally
      related gene sets under different subsets of experimental conditions. In this
      context, recognizing groups of co-expressed or co-regulated genes, that is, genes
      which follow a similar expression pattern, is one of the main objectives. Due to
      the problem complexity, heuristic searches are usually used instead of exhaustive
      algorithms. Furthermore, most of biclustering approaches use a measure or cost
      function that determines the quality of biclusters. Having a suitable quality
      metric for bicluster is a critical aspect, not only for guiding the search, but
      also for establishing a comparison criteria among the results obtained by
      different biclustering techniques. In this paper, we analyse a large number of
      existing approaches to quality measures for gene expression biclusters, as well
      as we present a comparative study of them based on their capability to recognize
      different expression patterns in biclusters. 

PMID- 25763841
TI  - Functional characteristics of the brain in college students with internet gaming
      disorder.
AB  - Internet gaming disorder (IGD) is a subtype of internet addiction disorder (IAD),
      but its pathogenesis remains unclear. This study investigated brain function in
      IGD individuals using task-state functional magnetic resonance imaging (fMRI). It
      is a prospective study in 19 IGD individuals and 19 matched healthy controls.
      They all received internet videogame stimuli while a 3.0 T fMRI was used to
      assess echo planar imaging. Brain activity was analyzed using the Brain Voyager
      software package. Functional data were spatially smoothed using Gaussian kernel.
      The threshold level was positioned at 10 pixels, and the activation range
      threshold was set to 10 voxels. Activated brain regions were compared between the
      two groups, as well as the amount of activated voxels. The internet videogame
      stimuli activated brain regions in both groups. Compared with controls, the IGD
      group showed increased activation in the right superior parietal lobule, right
      insular lobe, right precuneus, right cingulated gyrus, right superior temporal
      gyrus, and left brainstem. There was a significant difference in the number of
      activated voxels between the two groups. An average of 1078 voxels was activated
      in the IGD group compared with only 232 in the control group. Internet videogame
      play activates the vision, space, attention, and execution centers located in the
      occipital, temporal, parietal, and frontal gyri. Abnormal brain function was
      noted in IGD subjects, with hypofunction of the frontal cortex. IGD subjects
      showed laterality activation of the right cerebral hemisphere.

PMID- 25763840
TI  - Functional integration of human neural precursor cells in mouse cortex.
AB  - This study investigates the electrophysiological properties and functional
      integration of different phenotypes of transplanted human neural precursor cells
      (hNPCs) in immunodeficient NSG mice. Postnatal day 2 mice received unilateral
      injections of 100,000 GFP+ hNPCs into the right parietal cortex. Eight weeks
      after transplantation, 1.21% of transplanted hNPCs survived. In these hNPCs,
      parvalbumin (PV)-, calretinin (CR)-, somatostatin (SS)-positive inhibitory
      interneurons and excitatory pyramidal neurons were confirmed
      electrophysiologically and histologically. All GFP+ hNPCs were immunoreactive
      with anti-human specific nuclear protein. The proportions of PV-, CR-, and SS
      positive cells among GFP+ cells were 35.5%, 15.7%, and 17.1%, respectively;
      around 15% of GFP+ cells were identified as pyramidal neurons. Those
      electrophysiologically and histological identified GFP+ hNPCs were shown to fire
      action potentials with the appropriate firing patterns for different classes of
      neurons and to display spontaneous excitatory and inhibitory postsynaptic
      currents (sEPSCs and sIPSCs). The amplitude, frequency and kinetic properties of
      sEPSCs and sIPSCs in different types of hNPCs were comparable to host cells of
      the same type. In conclusion, GFP+ hNPCs produce neurons that are competent to
      integrate functionally into host neocortical neuronal networks. This provides
      promising data on the potential for hNPCs to serve as therapeutic agents in
      neurological diseases with abnormal neuronal circuitry such as epilepsy. 

PMID- 25763842
TI  - Serum Thyroglobulin Measured With a Second-Generation Assay in Patients
      Undergoing Total Thyroidectomy Without Radioiodine Remnant Ablation: A
      Prospective Study.
AB  - BACKGROUND: Follow-up consisting of the measurement of nonstimulated serum
      thyroglobulin (Tg) combined with neck ultrasonography is recommended for patients
      with papillary thyroid carcinoma without indication for radioiodine ablation.
      There is no recommendation of thyrotropin suppression during this follow-up. New
      generation Tg assays have been increasingly used, but few studies involve
      patients submitted only to thyroidectomy and they have several limitations. The
      objective of this prospective study was to define expected concentrations of
      nonstimulated Tg measured with a second-generation assay after total
      thyroidectomy in the absence of tumor. METHODS: Serum Tg was measured using a
      second-generation assay in 69 patients without tumor and serum thyrotropin
      between 0.5 and 2 mIU/L, 3, 6, 12, and 24 months after total thyroidectomy. All
      patients had undetectable anti-Tg antibodies. RESULTS: Serum Tg was undetectable
      in 44.4%, 57%, 62.5%, and 62.1% of the patients 3, 6, 12, and 24 months after
      thyroidectomy, respectively, and was <=0.5 ng/mL in 60.3%, 80%, 90.6%, and 90.9%
      of patients. All patients had a Tg<=2 ng/mL 6 months after thyroidectomy, and 97%
      had a Tg<=1 ng/mL 24 months after surgery. There was no case of Tg conversion
      from undetectable to detectable and none of the patients presented an increase in
      Tg. CONCLUSIONS: An important decline in serum Tg occurred between 3 and 6 months
      after total thyroidectomy. One year after surgery, Tg was undetectable in
      approximately 60% of the patients and was <=2 ng/mL in all of them.

PMID- 25763843
TI  - Diabetes-related distress over the course of illness: results from the Diacourse
      study.
AB  - AIMS: To investigate the relationship between diabetes duration and diabetes
      related distress and to examine the impact of micro- and macrovascular
      complications and blood glucose-lowering treatment on this relationship. METHODS:
      We conducted a cross-sectional study in people with Type 2 diabetes who
      participated in the Dutch Diacourse study (n = 590) and completed the Problem
      Areas in Diabetes questionnaire. Data on diabetes duration, micro- and
      macrovascular complications and blood glucose-lowering treatment were collected.
      Multiple linear regression analysis was used to investigate the association
      between diabetes duration and diabetes-related distress, and to examine whether
      complications and treatment could explain this association. RESULTS: A
      significant linear and quadratic association between diabetes duration and
      diabetes-related distress was found (duration: beta = 0.27, P = 0.005;
      duration(2): beta = -0.21, P = 0.030). The association between duration and
      distress could be explained by microvascular complications and insulin treatment,
      which were both more often present in people with a longer diabetes duration, and
      were associated with higher levels of diabetes-related distress (beta = 0.20, P <
      0.001 and beta = 0.16, P = 0.006 respectively). Duration, age, gender,
      complications and treatment together explained 13.1% of the variance in distress.
      CONCLUSIONS: Diabetes duration was associated with diabetes-related distress.
      This association can be explained largely by the presence of diabetes-related
      microvascular complications and insulin treatment. Healthcare providers should
      focus on distress in people with Type 2 diabetes in different stages over the
      course of illness, especially when complications are present or when people are
      on insulin treatment. As well as diabetes duration, complications and blood
      glucose-lowering treatment, diabetes-related distress is likely to be influenced
      by many other factors.

PMID- 25763844
TI  - Periorbital cellulitis due to cutaneous anthrax.
AB  - Virgil's plague of the ancient world, Bacillus anthracis, is rare in developed
      nations. Unfortunately rural communities across the globe continue to be exposed
      to this potentially lethal bacterium. Herein we report a case of periorbital
      cutaneous anthrax infection in a 3-year-old girl from the rural area surrounding
      Harare, Zimbabwe with a brief review of the literature. 

PMID- 25763845
TI  - Breastfeeding failure secondary to idiopathic isolated prolactin deficiency:
      report of two cases.

PMID- 25763846
TI  - Seizures are regulated by ubiquitin-specific peptidase 9 X-linked (USP9X), a de
      ubiquitinase.
AB  - Epilepsy is a common disabling disease with complex, multifactorial genetic and
      environmental etiology. The small fraction of epilepsies subject to Mendelian
      inheritance offers key insight into epilepsy disease mechanisms; and pathologies
      brought on by mutations in a single gene can point the way to generalizable
      therapeutic strategies. Mutations in the PRICKLE genes can cause seizures in
      humans, zebrafish, mice, and flies, suggesting the seizure-suppression pathway is
      evolutionarily conserved. This pathway has never been targeted for novel anti
      seizure treatments. Here, the mammalian PRICKLE-interactome was defined,
      identifying prickle-interacting proteins that localize to synapses and a novel
      interacting partner, USP9X, a substrate-specific de-ubiquitinase. PRICKLE and
      USP9X interact through their carboxy-termini; and USP9X de-ubiquitinates PRICKLE,
      protecting it from proteasomal degradation. In forebrain neurons of mice, USP9X
      deficiency reduced levels of Prickle2 protein. Genetic analysis suggests the same
      pathway regulates Prickle-mediated seizures. The seizure phenotype was suppressed
      in prickle mutant flies by the small-molecule USP9X inhibitor, Degrasyn/WP1130,
      or by reducing the dose of fat facets a USP9X orthologue. USP9X mutations were
      identified by resequencing a cohort of patients with epileptic encephalopathy,
      one patient harbored a de novo missense mutation and another a novel coding
      mutation. Both USP9X variants were outside the PRICKLE-interacting domain. These
      findings demonstrate that USP9X inhibition can suppress prickle-mediated seizure
      activity, and that USP9X variants may predispose to seizures. These studies point
      to a new target for anti-seizure therapy and illustrate the translational power
      of studying diseases in species across the evolutionary spectrum. 

PMID- 25763847
TI  - Diagnostic accuracy of physical examination for anterior knee instability: a
      systematic review.
AB  - PURPOSE: Determining diagnostic accuracy of Lachman, pivot shift and anterior
      drawer tests versus gold standard diagnosis (magnetic resonance imaging or
      arthroscopy) for anterior cruciate ligament (ACL) insufficiency cases.
      Secondarily, evaluating effects of: chronicity, partial rupture, awake versus
      anaesthetized evaluation. METHODS: Searching MEDLINE, EMBASE and PubMed
      identified studies on diagnostic accuracy for ACL insufficiency. Studies
      identification and data extraction were performed in duplicate. Quality
      assessment used QUADAS tool, and statistical analyses were completed for pooled
      sensitivity and specificity. RESULTS: Eight studies were included. Given
      insufficient data, pooled analysis was only possible for sensitivity on Lachman
      and pivot shift test. During awake evaluation, sensitivity for the Lachman test
      was 89 % (95 % CI 0.76, 0.98) for all rupture types, 96 % (95 % CI 0.90, 1.00)
      for complete ruptures and 68 % (95 % CI 0.25, 0.98) for partial ruptures. For
      pivot shift in awake evaluation, results were 79 % (95 % CI 0.63, 0.91) for all
      rupture types, 86 % (95 % CI 0.68, 0.99) for complete ruptures and 67 % (95 % CI
      0.47, 0.83) for partial ruptures. CONCLUSION: Decreased sensitivity of Lachman
      and pivot shift tests for partial rupture cases and for awake patients raised
      suspicions regarding the accuracy of these tests for diagnosis of ACL
      insufficiency. This may lead to further research aiming to improve the
      understanding of the true accuracy of these physical diagnostic tests and
      increase the reliability of clinical investigation for this pathology. LEVEL OF
      EVIDENCE: IV.

PMID- 25763848
TI  - Does patellofemoral geometry in TKA affect patellar position in mid-flexion?
AB  - PURPOSE: This study aimed to compare the position of the patella at 90 degrees 
      of flexion before and after implantation of two TKA models with identical
      tibiofemoral geometry but different trochlear and patellar designs. The
      hypothesis was that the design with the deeper 'anatomic' trochlea could produce
      more natural patellar positions. METHODS: Intra-operative navigation data were
      collected from 22 consecutive cases that received two TKA designs (9 HLS
      Noetos((r)) and 13 HLS KneeTec((r))). Both implants were cemented postero
      stabilised TKAs with mobile tibial inserts and patellar resurfacing. Operations
      were guided by a non-image-based system that recorded relative femoral, tibial
      and patellar positions pre- and post-operatively. RESULTS: The two groups
      exhibited little difference in femoral internal-external rotation and anterior
      posterior translation during knee flexion. The two groups exhibited significant
      differences in patellar position at 90 degrees  of flexion. Post-operatively, the
      patella was similarly shifted medially relative to the femur (Noetos 6.9 mm,
      KneeTec 6.0 mm, n.s.). Patellar flexion was equivalent in native knees (Noetos
      18.3 degrees , KneeTec 20.5 degrees , n.s.), but in implanted knees, it was
      considerably different (Noetos 6.3 degrees , KneeTec 23.5 degrees , p = 0.031).
      CONCLUSIONS: The present study compared intra-operative navigation data from two
      patient series that received TKA implants with identical tibiofemoral articular
      geometry but different patellofemoral designs. The results confirm that
      tibiofemoral kinematics are unchanged, but that patellar positions at 90 degrees 
      of flexion offer greater mechanical advantage to the quadriceps using the KneeTec
      than using the Noetos. The findings raise awareness of influence of
      patellofemoral geometry on mid-flexion kinematics and help surgeons select the
      most suitable implant for patients with weak quadriceps muscles or with history
      of patellar instability. LEVEL OF EVIDENCE: Comparative study, Level III.

PMID- 25763849
TI  - Arthroscopic single-bundle anterior cruciate ligament reconstruction with six
      strand hamstring tendon allograft versus bone-patellar tendon-bone allograft.
AB  - PURPOSE: The aim of this study was to compare the clinical outcomes of
      arthroscopic single-bundle anterior cruciate ligament (ACL) reconstruction with
      six-strand hamstring tendon (HT) allograft versus bone-patellar tendon-bone
      (BPTB) allograft. METHODS: The prospective randomized controlled trial was
      included 129 patients. Sixty-nine patients received reconstruction with six
      strand HT allografts (HT group), whereas 60 patients with BPTB allografts (BPTB
      group). Outcome assessment included re-rupture findings, International Knee
      Documentation Committee (IKDC) scores, Lysholm scores, KT-1000 arthrometer,
      Lachman test, pivot-shift test, range of motion (ROM) and single-leg hop test.
      RESULTS: At a mean follow-up of 52 months, 113 patients (HT group, 61 patients;
      BPTB group, 52 patients) completed a minimum 4-year follow-up. Four patients in
      HT group and six in BPTB group experienced ACL re-rupture (6.2 vs. 10.3 %) and
      received revision surgery. Significant between-group differences were observed in
      KT-1000 outcomes and pivot-shift test 1 (1.2 +/- 1.5 vs. 1.8 +/- 1.3, p = 0.025;
      positive rate 6.5 vs. 18.9 %, p = 0.036), 2 (1.1 +/- 1.4 vs. 1.6 +/- 1.2, p =
      0.044; 8.1 vs. 20.7 %, p = 0.039), 4 (1.1 +/- 1.5 vs. 1.7 +/- 1.4, p = 0.031; 9.7
      vs. 25 %, p = 0.012) years postoperatively. The outcomes between the two groups
      were comparable in terms of IKDC scores, Lysholm scores, Lachman test, ROM and
      single-leg hop test. CONCLUSIONS: Six-strand HT allograft achieved superior
      anteroposterior and rotational stability after single-bundle ACL reconstruction.
      It is a reasonable graft substitute for ACL reconstruction. LEVEL OF EVIDENCE:
      II.

PMID- 25763850
TI  - Changes in posterior tibial slope angle in patients undergoing open-wedge high
      tibial osteotomy for varus gonarthrosis.
AB  - PURPOSE: In this study, postoperative changes in the posterior tibial slope angle
      and clinical outcomes following open-wedge high tibial osteotomy were evaluated.
      METHODS: This study included 39 knees (18 left, 21 right) of 35 patients (three
      male, 32 female; median age, 53 years; age range 37-64 years) with symptomatic
      isolated medial joint osteoarthritis who underwent open-wedge high tibial
      osteotomy and fixation with a Puddu plate. The patients were clinically assessed
      according to the Lysholm knee score, a visual analogue pain scale, and a patient
      satisfaction questionnaire. Radiological assessment was made according to the
      changes in the posterior tibial slope angle and the correlation between these
      changes and clinical signs. The median follow-up period was 11 years (range 7-14
      years). RESULTS: Significant improvements were observed in the preoperative and
      postoperative clinical scores of the Lysholm knee scale, visual analogue pain
      scale, and patient satisfaction questionnaire (p < 0.05). Radiological assessment
      showed that the posterior tibial slope angle was significantly higher during the
      postoperative and follow-up periods (p  0.05). There was no correlation between
      the postoperative Lysholm scores and the increase in the posterior tibial slope
      angle (p = n.s.). CONCLUSIONS: We conclude that both the conventional Puddu plate
      design and its anteromedial plate placement are what increase the tibial slope
      after an opening-wedge proximal tibial osteotomy. Therefore, current new plate
      design may help preserve the posterior tibial slope angle. LEVEL OF EVIDENCE: IV.

PMID- 25763851
TI  - Factors affecting intraoperative kinematic patterns and flexion angles in
      navigated total knee arthroplasty.
AB  - PURPOSE: To investigate the factors affecting intraoperative kinematics, as
      measured with a navigation system, and their effect on maximum flexion angles
      during total knee arthroplasty (TKA). METHOD: One hundred posterior stabilised
      (PS) TKAs performed using an image-free navigation system were evaluated. Tibial
      internal rotation angles at maximum extension, 30 degrees , 45 degrees , 60
      degrees , 90 degrees , and maximum flexion were collected at registration and
      after implantation. The varus angles from the coronal mechanical axis were also
      collected. The rotational patterns were divided into four groups to investigate
      whether flexion contracture and varus deformity affected the kinematic patterns,
      and correlated with the maximum pre- and post-operative flexion angles. RESULTS:
      At registration, the flexion angles at maximum extension differed significantly
      between the kinematic groups; the flexion angle at maximum extension at
      registration was negatively correlated with the pre-operative maximum flexion
      angle (R(2) = 0.226, p < 0.0001) and the post-operative maximum flexion angle
      (R(2) = 0.059, p = 0.0167). Varus deformity at registration also differed
      significantly between the kinematic groups; varus deformity at registration was
      negatively correlated with the pre-operative maximum flexion angle (R(2) = 0.087,
      p = 0.0036) and post-operative maximum flexion angle (R(2) = 0.101, p = 0.0027).
      CONCLUSION: Navigation-based measurements in patients undergoing PS TKA indicated
      that pre-operative flexion contracture and varus deformity are negatively
      correlated with both pre- and post-operative maximum flexion angles. The results
      may improve the ease with which surgeons can interpret intraoperative kinematics,
      by providing a multi-dimensional perspective. With further knowledge regarding
      intraoperative kinematics, it might be possible to improve surgical approach,
      prosthesis design, and clinical outcomes. LEVEL OF EVIDENCE: II.

PMID- 25763852
TI  - Behind-remnant arthroscopic observation and scoring of femoral attachment of
      injured anterior cruciate ligament.
AB  - PURPOSE: To describe the femoral anterior cruciate ligament (ACL) attachment
      based on the behind-remnant observation with a new scoring system and to
      investigate the characteristics of an ACL injured knee. METHODS: One hundred and
      twenty-six ACL injured knees with four standardized arthroscopic photos and full
      evaluation under anaesthesia were included in the study. Sixty non-ACL injured
      knees were also evaluated as control. A scoring system for the femoral ACL
      attachment was set as follows based on behind-remnant findings; the direct
      insertion was divided into three portions as proximal, middle and distal. The
      fibrous extension from the articular surface (indirect insertion) and the
      severity of synovitis were also graded into 2, 1 and 0 points. The total score
      was 10 as full marks. The correlation between each score and total score, as well
      as age at surgery, gender, anterior laxity, pivot-shift test and meniscus
      injuries, was statistically evaluated with a significance of 0.05. RESULTS: The
      femoral attachment score of the ACL injured knees was statistically different
      from that of the non-ACL injured knees. Anterior laxity was dependent only on the
      integrity of the proximal portion. Knee instability was significantly correlated
      with the status of the direct insertion. Medial and lateral meniscus injuries
      were correlated with the middle part and the distal part of the direct insertion,
      respectively. The direct insertion was less preserved in distal and articular
      sides. CONCLUSION: Arthroscopic observation behind the remnant of the injured ACL
      showed clearer findings of the femoral attachment than that from the front.
      Behind-remnant observation greatly assists in the creation of a correct
      anatomical tunnel with the preserving remnant. The scoring system indicated
      several significant correlations between the score and preoperative patient
      status.

PMID- 25763853
TI  - Clinical and MRI outcomes of HA injection following arthroscopic microfracture
      for osteochondral lesions of the talus.
AB  - PURPOSE: The purpose of this study was to compare the clinical and magnetic
      resonance imaging (MRI) outcomes of arthroscopic microfracture surgery alone or
      in combination with hyaluronic acid (HA) injection in the treatment of
      osteochondral lesions of the talus. METHODS: Thirty-five patients with
      osteochondral lesions of the talus who underwent arthroscopic microfracture were
      included and followed up for at least 9 months post-operatively. The patients
      were randomly divided into non-injection group (n = 17) who received treatment
      with microfracture surgery alone and injection group (n = 18) who also accepted
      intra-articular injection of HA post-operatively. Quantitative MRI was used to
      evaluate the cartilage repair after surgery. American Orthopaedic Foot and Ankle
      Society (AOFAS) Ankle-Hind foot Scale scores and Visual Analogue Scale (VAS)
      scores were used to evaluate clinical outcomes. RESULTS: After operation, the MRI
      outcomes showed that the thickness index was higher (0.8 +/- 0.1 vs. 0.7 +/- 0.1)
      and the T2 index was lower (1.2 +/- 0.1 vs. 1.4 +/- 0.1) in the injection group
      than in the non-injection group (P < 0.01). As for the volumes of subchondral
      bone marrow oedema, there are no significant differences between groups (n.s.).
      Compared with the non-injection group, the AOFAS score and the VAS score yielded
      a higher level of improvement in injection group at final follow-up post
      operatively (P < 0.05). CONCLUSIONS: Arthroscopic microfracture is a safe and
      effective procedure for osteochondral lesions of the talus. Intra-articular HA
      injection as an adjunct to arthroscopic microfracture might offer better
      functional recovery than microfracture alone. LEVEL OF EVIDENCE: II.

PMID- 25763855
TI  - Developmental competence of 8?16-cell stage bison embryos produced by
      interspecies somatic cell nuclear transfer.
AB  - Altered communication between nuclear and cytoplasmic components has been linked
      to impaired development in interspecies somatic cell nuclear transfer (iSCNT)
      embryos as a result of genetic divergence between the two species. This study
      investigated the developmental potential and mitochondrial function of cattle
      (Bos taurus), plains bison (Bison bison bison) and wood bison (Bison bison
      athabascae) embryos produced by iSCNT using domestic cattle oocytes as
      cytoplasts. Embryos in all groups were analysed for development, accumulation of
      ATP, apoptosis and gene expression of nuclear- and mitochondrial-encoded genes at
      the 8-16-cell stage. The results of this study showed no significant differences
      in the proportion of developed embryos at the 2-, 4- and 8-16-cell stages between
      groups. However, significantly higher ATP levels were observed in cattle SCNT
      embryos compared with bison iSCNT embryos. Significantly more condensed and
      terminal deoxynucleotidyl transferase-mediated dUTP nick-end labelling (TUNEL)
      positive nuclei were found in plains bison iSCNT embryos. No significant
      differences in the expression levels of nuclear respiratory factor 2 (NRF2) or
      mitochondrial subunit 2 of cytochrome c oxidase (mt-COX2) were found in any of
      the groups. However, mitochondrial transcription factor A (TFAM) expression
      significantly differed between groups. The results of this study provide insights
      into the potential causes that might lead to embryonic arrest in bison iSCNT
      embryos, including mitochondrial dysfunction, increased apoptosis and abnormal
      gene expression.

PMID- 25763854
TI  - Differential effect of phosphorylation-defective survivin on radiation response
      in estrogen receptor-positive and -negative breast cancer.
AB  - Survivin is a key member of the inhibitor of apoptosis protein family, and is
      considered a promising therapeutic target due to its universal overexpression in
      cancers. Survivin is implicated in cellular radiation response through its role
      in apoptosis, cell division, and DNA damage response. In the present study,
      analysis of publically available data sets showed that survivin gene expression
      increased with breast cancer stage (p < 0.00001) and was significantly higher in
      estrogen receptor-negative cancers as compared to estrogen receptor-positive
      cancers (p = 9e-46). However, survivin was prognostic in estrogen receptor
      positive tumors (p = 0.03) but not in estrogen receptor-negative tumors (p =
      0.28). We assessed the effect of a survivin dominant-negative mutant on colony
      formation (2D) and mammosphere-formation (3D) efficiency, and radiation response
      in the estrogen receptor-positive MCF7 and estrogen receptor-negative SUM149
      breast cancer cell lines. The colony-formation efficiency was significantly lower
      in the dominant-negative survivin-transduced cells versus control MCF7 cells
      (0.42 vs. 0.58, p < 0.01), but it was significantly higher in dominant-negative
      population versus control-transduced SUM149 cells (0.29 vs. 0.20, p < 0.01). A
      similar, non-significant, trend in mammosphere-formation efficiency was observed.
      We compared the radiosensitivity of cells stably expressing dominant-negative
      survivin with their controls in both cell lines under 2D and 3D culture
      conditions following exposure to increasing doses of radiation. We found that the
      dominant-negative populations were radioprotective in MCF7 cells but
      radiosensitive in SUM149 cells compared to the control-transduced population;
      further, Taxol was synergistic with the survivin mutant in SUM149 but not MCF7.
      Our data suggests that survivin modulation influences radiation response
      differently in estrogen receptor-positive and estrogen receptor-negative breast
      cancer subtypes, warranting further investigation. 

PMID- 25763856
TI  - Executive and attentional contributions to Theory of Mind deficit in attention
      deficit/hyperactivity disorder (ADHD).
AB  - Attention deficit/hyperactivity disorder (ADHD) in children has been associated
      with attentional and executive problems, but also with socioemotional
      difficulties possibly associated with deficits in Theory of Mind (ToM).
      Socioemotional problems in ADHD are associated with more negative prognoses,
      notably interpersonal, educational problems, and an increased risk of developing
      other psychiatric disorders that emphasize the need to clarify the nature of
      their ToM deficits. In this study, we hypothesized that ToM dysfunction in
      children with ADHD is largely attributable to their attentional and/or executive
      deficits. Thirty-one children with ADHD (8-12 years, IQ > 85) and 31 typically
      developing (TD) children were assessed using executive functions (inhibition,
      planning, and flexibility) and attentional tasks, as well as two advanced ToM
      tasks (Reading the Mind in the Eyes and Faux Pas) involving different levels of
      executive control. Children with ADHD performed more poorly than TD children in
      attentional, executive function, and ToM tasks. Linear regression analyses
      conducted in the ADHD group indicated that inhibition scores predicted
      performance on the "Faux Pas" task the best, while attention scores were the best
      for predicting performance on the Reading the Mind in the Eyes task. When
      controlled for inhibition and attentional variables, ToM performance in children
      with ADHD was actually similar to TD children. Contrarily, controlling for ToM
      scores did not normalize performance for inhibition and attentional tasks in
      children with ADHD. This unidirectional relationship suggests that deficits in
      the EF and attentional domains are responsible for ToM deficits in ADHD, which
      therefore may contribute to their socioemotional difficulties. 

PMID- 25763857
TI  - MicroRNA profiling of pericardial fluid samples from patients with heart failure.
AB  - AIMS: Multicellular organisms maintain vital functions through intercellular
      communication. Release of extracellular vesicles that carry signals to even
      distant target organs is one way of accomplishing this communication. MicroRNAs
      can also be secreted from the cells in exosomes and act as paracrine signalling
      molecules. In addition, microRNAs have been implicated in the pathogenesis of a
      large number of diseases, including cardiovascular diseases, and are considered
      as promising candidate biomarkers due to their relative stability and easy
      quantification from clinical samples. Pericardial fluid contains hormones
      secreted by the heart and is known to reflect the cardiac function. In this
      study, we sought to investigate whether pericardial fluid contains microRNAs and
      if so, whether they could be used to distinguish between different cardiovascular
      pathologies and disease stages. METHODS AND RESULTS: Pericardial fluid was
      collected from heart failure patients during open-heart surgery. MicroRNA
      profiles of altogether 51 patients were measured by quantitative real-time PCR
      (qPCR) using Exiqon human panels I and II. On the average, 256 microRNAs were
      detected per sample, and 70 microRNAs out of 742 profiled microRNAs were detected
      in every sample. The five most abundant microRNAs in pericardial fluid were miR
      21-5p, miR-451a, miR-125b-5p, let-7b-5p and miR-16-5p. No specific signatures for
      cardiovascular pathologies or clinically assessed heart failure stages could be
      detected from the profiles and, overall, microRNA profiles of the samples were
      found to be very similar despite the heterogeneity in the study population.
      CONCLUSION: Measured microRNA profiles did not separate the samples according to
      the clinical features of the patients. However, several previously identified
      heart failure marker microRNAs were detected. The pericardial fluid microRNA
      profile appeared to be a result of an active and selective secretory process
      indicating that microRNAs may act as paracrine signalling factors by mediating
      the local crosstalk between cardiac cells.

PMID- 25763858
TI  - Tool compounds robustly increase turnover of an artificial substrate by
      glucocerebrosidase in human brain lysates.
AB  - Mutations in glucocerebrosidase (GBA1) cause Gaucher disease and also represent a
      common risk factor for Parkinson's disease and Dementia with Lewy bodies.
      Recently, new tool molecules were described which can increase turnover of an
      artificial substrate 4MUG when incubated with mutant N370S GBA1 from human
      spleen. Here we show that these compounds exert a similar effect on the wild-type
      enzyme in a cell-free system. In addition, these tool compounds robustly increase
      turnover of 4MUG by GBA1 derived from human cortex, despite substantially lower
      glycosylation of GBA1 in human brain, suggesting that the degree of glycosylation
      is not important for compound binding. Surprisingly, these tool compounds failed
      to robustly alter GBA1 turnover of 4MUG in the mouse brain homogenate. Our data
      raise the possibility that in vivo models with humanized glucocerebrosidase may
      be needed for efficacy assessments of such small molecules. 

PMID- 25763859
TI  - Relative invasion risk for plankton across marine and freshwater systems:
      examining efficacy of proposed international ballast water discharge standards.
AB  - Understanding the implications of different management strategies is necessary to
      identify best conservation trajectories for ecosystems exposed to anthropogenic
      stressors. For example, science-based risk assessments at large scales are needed
      to understand efficacy of different vector management approaches aimed at
      preventing biological invasions associated with commercial shipping. We conducted
      a landscape-scale analysis to examine the relative invasion risk of ballast water
      discharges among different shipping pathways (e.g., Transoceanic, Coastal or
      Domestic), ecosystems (e.g., freshwater, brackish and marine), and timescales
      (annual and per discharge event) under current and future management regimes. The
      arrival and survival potential of nonindigenous species (NIS) was estimated based
      on directional shipping networks and their associated propagule pressure,
      environmental similarity between donor-recipient ecosystems (based on salinity
      and temperature), and effects of current and future management strategies (i.e.,
      ballast water exchange and treatment to meet proposed international biological
      discharge standards). Our findings show that current requirements for ballast
      water exchange effectively reduce invasion risk to freshwater ecosystems but are
      less protective of marine ecosystems because of greater environmental mismatch
      between source (oceanic) and recipient (freshwater) ecoregions. Future
      requirements for ballast water treatment are expected to reduce risk of
      zooplankton NIS introductions across ecosystem types but are expected to be less
      effective in reducing risk of phytoplankton NIS. This large-scale risk assessment
      across heterogeneous ecosystems represents a major step towards understanding the
      likelihood of invasion in relation to shipping networks, the relative efficacy of
      different invasion management regimes and seizing opportunities to reduce the
      ecological and economic implications of biological invasions. 

PMID- 25763860
TI  - Advance directives for older adults in the emergency department: a systematic
      review.
AB  - BACKGROUND: It has been more than two decades since the passage of the Patient
      Self-Determination Act (PSDA) of 1991, an act that requires many medical points
      of care, including emergency departments (EDs), to provide information to
      patients about advance directives (ADs). OBJECTIVE: The study objective was to
      determine the prevalence of ADs among ED patients with a focus on older adults
      and factors associated with rates of completion. METHODS: We searched PubMed,
      Embase, PsycINFO, CINAHL, Web of Science, Medline, and the Cochrane Library.
      Articles were selected according to the following criteria: (1) population: adult
      ED patients; (2) outcome measures: quantitative prevalence data pertaining to ADs
      and factors associated with completion of an AD; (3) location: EDs in the United
      States; and (4) date: published 1991 or later. RESULTS: Of the 258 references
      retrieved as a result of our search, six studies met inclusion criteria. Rates of
      patient-reported AD completion ranged from 21% to 53%, while ADs were available
      to ED personnel for 1% to 44% of patients. Patients aged >=65 years had ADs 21%
      to 46% of the time. Sociodemographics (e.g., older age, specific religion, white
      or African American race, being widowed, or having children) and health status
      related variables (e.g., poor health, institutionalization, and having a primary
      care provider) were associated with greater likelihood of having an AD.
      CONCLUSIONS: Published rates of AD completion vary widely among patients
      presenting to U.S. EDs. Patient sociodemographic and health status factors are
      associated with increased rates of AD completion, though rates are low for all
      populations.

PMID- 25763862
TI  - Comparative efficacy of golimumab, infliximab, and adalimumab for moderately to
      severely active ulcerative colitis: a network meta-analysis accounting for
      differences in trial designs.
AB  - AIM: To conduct a network meta-analysis (NMA) to establish the comparative
      efficacy of infliximab, adalimumab and golimumab for the treatment of moderately
      to severely active ulcerative colitis (UC). DESIGN: A systematic literature
      search identified five randomized controlled trials for inclusion in the NMA. One
      trial assessed golimumab, two assessed infliximab and two assessed adalimumab.
      Outcomes included clinical response, clinical remission, mucosal healing,
      sustained clinical response and sustained clinical remission. Innovative methods
      were used to allow inclusion of the golimumab trial data given the alternative
      design of this trial (i.e., two-stage re-randomization). RESULTS: After
      induction, no statistically significant differences were found between golimumab
      and adalimumab or between golimumab and infliximab. Infliximab was statistically
      superior to adalimumab after induction for all outcomes and treatment ranking
      suggested infliximab as the superior treatment for induction. Golimumab and
      infliximab were associated with similar efficacy for achieving maintained
      clinical remission and sustained clinical remission, whereas adalimumab was not
      significantly better than placebo for sustained clinical remission. Golimumab and
      infliximab were also associated with similar efficacy for achieving maintained
      clinical response, sustained clinical response and mucosal healing. Finally,
      golimumab 50 and 100 mg was statistically superior to adalimumab for clinical
      response and sustained clinical response, and golimumab 100 mg was also
      statistically superior to adalimumab for mucosal healing. CONCLUSION: The results
      of our NMA suggest that infliximab was statistically superior to adalimumab after
      induction, and that golimumab was statistically superior to adalimumab for
      sustained outcomes. Golimumab and infliximab appeared comparable in efficacy.

PMID- 25763863
TI  - Child Modifiability as a Predictor of Language Abilities in Deaf Children Who Use
      American Sign Language.
AB  - PURPOSE: This research explored the use of dynamic assessment (DA) for language
      learning abilities in signing deaf children from deaf and hearing families.
      METHOD: Thirty-seven deaf children, aged 6 to 11 years, were identified as either
      stronger (n = 26) or weaker (n = 11) language learners according to teacher or
      speech-language pathologist report. All children received 2 scripted, mediated
      learning experience sessions targeting vocabulary knowledge-specifically, the use
      of semantic categories that were carried out in American Sign Language.
      Participant responses to learning were measured in terms of an index of child
      modifiability. This index was determined separately at the end of the 2
      individual sessions. It combined ratings reflecting each child's learning
      abilities and responses to mediation, including social-emotional behavior,
      cognitive arousal, and cognitive elaboration. RESULTS: Group results showed that
      modifiability ratings were significantly better for stronger language learners
      than for weaker language learners. The strongest predictors of language ability
      were cognitive arousal and cognitive elaboration. CONCLUSION: Mediator ratings of
      child modifiability (i.e., combined score of social-emotional factors and
      cognitive factors) are highly sensitive to language-learning abilities in deaf
      children who use sign language as their primary mode of communication. This
      method can be used to design targeted interventions.

PMID- 25763861
TI  - Characterization and Early Detection of Balance Deficits in Fragile X Premutation
      Carriers With and Without Fragile X-Associated Tremor/Ataxia Syndrome (FXTAS).
AB  - Fragile X-associated tremor/ataxia syndrome (FXTAS) results from a "premutation"
      size 55-200 CGG repeat expansion in the fragile X mental retardation 1 (FMR1)
      gene. Core motor features include cerebellar gait ataxia and kinetic tremor,
      resulting in progressive mobility disability. There are no published studies
      characterizing balance deficits in FMR1 premutation carriers with and without
      FXTAS using a battery of quantitative measures to test the sensory integration
      underlying postural control, automatic postural reflexes, and dynamic postural
      stability limits. Computerized dynamic posturography (CDP) and two performance
      based balance measures were administered in 44 premutation carriers, 21 with
      FXTAS and 23 without FXTAS, and 42 healthy controls to compare balance and
      functional mobility between these groups. Relationships between FMR1 molecular
      variables, age, and sex and CDP scores were explored. FXTAS subjects demonstrated
      significantly lower scores on the sensory organization test (with greatest
      reductions in the vestibular control of balance), longer response latencies to
      balance perturbations, and reduced stability limits compared to controls.
      Premutation carriers without FXTAS also demonstrated significantly delayed
      response latencies and disrupted sensory weighting for balance control. Advancing
      age, male sex, increased CGG repeat size, and reduced X activation of the normal
      allele in premutation carrier women predicted balance dysfunction. These postural
      control deficits in carriers with and without FXTAS implicate dysfunctional
      cerebellar neural networks and may provide valuable outcome markers for tailored
      rehabilitative interventions. Our findings suggest that CDP may provide sensitive
      measures for early detection of postural control impairments in at-risk carriers
      and better characterize balance dysfunction and progression in FXTAS. 

PMID- 25763864
TI  - The origin of the variola virus.
AB  - The question of the origin of smallpox, one of the major menaces to humankind, is
      a constant concern for the scientific community. Smallpox is caused by the agent
      referred to as the variola virus (VARV), which belongs to the genus
      Orthopoxvirus. In the last century, smallpox was declared eradicated from the
      human community; however, the mechanisms responsible for the emergence of new
      dangerous pathogens have yet to be unraveled. Evolutionary analyses of the
      molecular biological genomic data of various orthopoxviruses, involving a wide
      range of epidemiological and historical information about smallpox, have made it
      possible to date the emergence of VARV. Comparisons of the VARV genome to the
      genomes of the most closely related orthopoxviruses and the examination of the
      distribution their natural hosts' ranges suggest that VARV emerged 3000 to 4000
      years ago in the east of the African continent. The VARV evolution rate has been
      estimated to be approximately 2 * 10-6 substitutions/site/year for the central
      conserved genomic region and 4 * 10-6 substitutions/site/year for the synonymous
      substitutions in the genome. Presumably, the introduction of camels to Africa and
      the concurrent changes to the climate were the particular factors that triggered
      the divergent evolution of a cowpox-like ancestral virus and thereby led to the
      emergence of VARV.

PMID- 25763866
TI  - A randomised, double blind trial of N-Acetylcysteine for hearing protection
      during stapes surgery.
AB  - BACKGROUND: Otosclerosis is a disorder that impairs middle ear function, leading
      to conductive hearing loss. Surgical treatment results in large improvement of
      hearing at low sound frequencies, but high-frequency hearing often suffers. A
      likely reason for this is that inner ear sensory cells are damaged by surgical
      trauma and loud sounds generated during the operation. Animal studies have shown
      that antioxidants such as N-Acetylcysteine can protect the inner ear from noise,
      surgical trauma, and some ototoxic substances, but it is not known if this works
      in humans. This trial was performed to determine whether antioxidants improve
      surgical results at high frequencies. METHODS: We performed a randomized, double
      blind and placebo-controlled parallel group clinical trial at three Swedish
      university clinics. Using block-stratified randomization, 156 adult patients
      undergoing stapedotomy were assigned to intravenous N-Acetylcysteine (150 mg/kg
      body weight) or matching placebo (1:1 ratio), starting one hour before surgery.
      The primary outcome was the hearing threshold at 6 and 8 kHz; secondary outcomes
      included the severity of tinnitus and vertigo. FINDINGS: One year after surgery,
      high-frequency hearing had improved 2.7 +/- 3.8 dB in the placebo group (67
      patients analysed) and 2.4 +/- 3.7 dB in the treated group (72 patients; means +/
      95% confidence interval, p = 0.54; linear mixed model). Surgery improved
      tinnitus, but there was no significant intergroup difference. Post-operative
      balance disturbance was common but improved during the first year, without
      significant difference between groups. Four patients receiving N-Acetylcysteine
      experienced mild side effects such as nausea and vomiting. CONCLUSIONS: N
      Acetylcysteine has no effect on hearing thresholds, tinnitus, or balance
      disturbance after stapedotomy. TRIAL REGISTRATION: ClinicalTrials.gov
      NCT00525551.

PMID- 25763865
TI  - Profiling of measles-specific humoral immunity in individuals following two doses
      of MMR vaccine using proteome microarrays.
AB  - INTRODUCTION: Comprehensive evaluation of measles-specific humoral immunity after
      vaccination is important for determining new and/or additional correlates of
      vaccine immunogenicity and efficacy. METHODS: We used a novel proteome microarray
      technology and statistical modeling to identify factors and models associated
      with measles-specific functional protective immunity in 150 measles vaccine
      recipients representing the extremes of neutralizing antibody response after two
      vaccine doses. RESULTS: Our findings demonstrate a high seroprevalence of
      antibodies directed to the measles virus (MV) phosphoprotein (P), nucleoprotein
      (N), as well as antibodies to the large polymerase (L) protein (fragment 1234 to
      1900 AA). Antibodies to these proteins, in addition to anti-F antibodies (and, to
      a lesser extent, anti-H antibodies), were correlated with neutralizing antibody
      titer and/or were associated with and predictive of neutralizing antibody
      response. CONCLUSION: Our results identify antibodies to specific measles virus
      proteins and statistical models for monitoring and assessment of measles-specific
      functional protective immunity in vaccinated individuals.

PMID- 25763867
TI  - Altered inhibitory control and increased sensitivity to cross-modal interference
      in tinnitus during auditory and visual tasks.
AB  - Tinnitus is the perception of sound in the absence of external stimulus.
      Currently, the pathophysiology of tinnitus is not fully understood, but recent
      studies indicate that alterations in the brain involve non-auditory areas,
      including the prefrontal cortex. In experiment 1, we used a go/no-go paradigm to
      evaluate the target detection speed and the inhibitory control in tinnitus
      participants (TP) and control subjects (CS), both in unimodal and bimodal
      conditions in the auditory and visual modalities. We also tested whether the
      sound frequency used for target and distractors affected the performance. We
      observed that TP were slower and made more false alarms than CS in all unimodal
      auditory conditions. TP were also slower than CS in the bimodal conditions. In
      addition, when comparing the response times in bimodal and auditory unimodal
      conditions, the expected gain in bimodal conditions was present in CS, but not in
      TP when tinnitus-matched frequency sounds were used as targets. In experiment 2,
      we tested the sensitivity to cross-modal interference in TP during auditory and
      visual go/no-go tasks where each stimulus was preceded by an irrelevant pre
      stimulus in the untested modality (e.g. high frequency auditory pre-stimulus in
      visual no/no-go condition). We observed that TP had longer response times than CS
      and made more false alarms in all conditions. In addition, the highest false
      alarm rate occurred in TP when tinnitus-matched/high frequency sounds were used
      as pre-stimulus. We conclude that the inhibitory control is altered in TP and
      that TP are abnormally sensitive to cross-modal interference, reflecting
      difficulties to ignore irrelevant stimuli. The fact that the strongest
      interference effect was caused by tinnitus-like auditory stimulation is
      consistent with the hypothesis according to which such stimulations generate
      emotional responses that affect cognitive processing in TP. We postulate that
      executive functions deficits play a key-role in the perception and maintenance of
      tinnitus. 

PMID- 25763868
TI  - Phenotypic differences of CD4(+) T cells in response to red blood cell
      immunization in transfused sickle cell disease patients.
AB  - Alloimmunization against red blood cells (RBCs) is the main immunological risk
      associated with transfusion in patients with sickle cell disease (SCD). However,
      about 50-70% of SCD patients never get immunized despite frequent transfusion. In
      murine models, CD4(+) T cells play a key role in RBC alloimmunization. We
      therefore explored and compared the CD4(+) T-cell phenotypes and functions
      between a group of SCD patients (n = 11) who never became immunized despite a
      high transfusion regimen and a group of SCD patients (n = 10) who had become
      immunized (at least against Kidd antigen b) after a low transfusion regimen. We
      studied markers of CD4(+) T-cell function, including TLR, that directly control
      lymphocyte function, and their spontaneous cytokine production. We also tested
      responders for the cytokine profile in response to Kidd antigen b peptides. Low
      TLR2/TLR3 expression and, unexpectedly, strong expression of CD40 on CD4(+) T
      cells were associated with the nonresponder status, whereas spontaneous
      expression of IL-10 by CD4(+) T cells and weak Tbet expression were associated
      with the responder status. A Th17 profile was predominant in responders when
      stimulated by Jb(k) . These findings implicate CD4(+) T cells in alloimmunization
      in humans and suggest that they may be exploited to differentiate responders from
      nonresponders.

PMID- 25763869
TI  - Pneumatosis intestinalis: a diagnostic dilemma.

PMID- 25763870
TI  - Two novel mutations of the ADAR1 gene in Chinese patients with dyschromatosis
      symmetrica hereditaria successfully treated with fractional CO2 laser.

PMID- 25763871
TI  - Correlation analysis of demographic and anthropometric factors, hip flexion angle
      and conus medullaris displacement with unilateral and bilateral straight leg
      raise.
AB  - PURPOSE: It has been shown that the conus medullaris displaces significantly and
      consistently in response to both unilateral and bilateral SLRs. Point of interest
      is represented by whether the magnitude of this displacement can be predicted in
      asymptomatic subjects. The purpose was to investigate whether any correlations
      existed between demographic and anthropometric factors and hip flexion angle with
      magnitude of conus medullaris displacement with the unilateral and bilateral SLR.
      This was done following the notion that there is the possibility that cord
      movement may contain aspects of predictability in asymptomatic subjects. METHODS:
      Using the same methods as in our previous MRI studies, we further investigated
      whether any correlations existed between age, height, weight, BMI or hip flexion
      angle and magnitude of conus medullaris displacement with the unilateral and
      bilateral SLR. RESULTS: Moderate to strong positive correlation was found between
      degree of hip flexion and magnitude of conus medullaris caudal displacement with
      unilateral and bilateral SLRs and CuMeD. A negligible inverse correlation between
      subjects' height and magnitude of conus medullaris displacement in response to
      unilateral SLR was found, while no correlation (r < 0.1) emerged with bilateral
      SLR and CuMeD. No correlation was found for other values such as age, weight or
      BMI. CONCLUSIONS: The data show that in in vivo and structurally intact
      asymptomatic volunteers, the degree of hip flexion may have strong predictive
      values for magnitude of neural displacement in response to unilateral and
      bilateral SLRs. This provides further justification to its quantification in
      clinical settings. Magnitude of conus medullaris displacement in response to
      unilateral and bilateral SLRs is not likely to be predicted from easily
      clinically collectable measures such as age, height, weight and BMI. This study
      offers information relevant to investigation of prediction of neuromechanical
      responses in neurodynamic tests.

PMID- 25763872
TI  - Sun skink landscape genomics: assessing the roles of micro-evolutionary processes
      in shaping genetic and phenotypic diversity across a heterogeneous and fragmented
      landscape.
AB  - Incorporating genomic data sets into landscape genetic analyses allows for
      powerful insights into population genetics, explicitly geographical correlates of
      selection, and morphological diversification of organisms across the geographical
      template. Here, we utilize an integrative approach to examine gene flow and
      detect selection, and we relate these processes to genetic and phenotypic
      population differentiation across South-East Asia in the common sun skink,
      Eutropis multifasciata. We quantify the relative effects of geographic and
      ecological isolation in this system and find elevated genetic differentiation
      between populations from island archipelagos compared to those on the adjacent
      South-East Asian continent, which is consistent with expectations concerning
      landscape fragmentation in island archipelagos. We also identify a pattern of
      isolation by distance, but find no substantial effect of ecological/environmental
      variables on genetic differentiation. To assess whether morphological
      conservatism in skinks may result from stabilizing selection on morphological
      traits, we perform FST -PST comparisons, but observe that results are highly
      dependent on the method of comparison. Taken together, this work provides novel
      insights into the manner by which micro-evolutionary processes may impact macro
      evolutionary scale biodiversity patterns across diverse landscapes, and provide
      genomewide confirmation of classic predictions from biogeographical and landscape
      ecological theory. 

PMID- 25763873
TI  - Rab5 activation as a tumor cell migration switch.
AB  - Increased cell migration is an acquired feature of metastatic cancer cells and
      relies on derailed signal transduction pathways. Intracellular vesicular
      trafficking plays a key role in cell migration due to its intricate involvement
      in cargo transport and membrane composition. In the last decade, endocytosis has
      been implicated in cell migration and found to be responsible for the
      internalization of membrane receptors at the plasma membrane, where integrin
      trafficking and fine-tuning of receptor tyrosine kinase signaling by
      internalization are major mechanisms. Accumulating evidence has suggested a link
      between endosome dynamics, cell migration, and invasion, in which small GTPases
      of the Rab family have central roles. We have recently determined that Rab5
      activation is a crucial event in promoting focal adhesion disassembly, which is
      concomitant with the migration and invasion of metastatic cancer cells. The
      mechanisms underlying this novel role for Rab5 are currently unclear, and their
      elucidation will provide insight into the role of Rab5 function in cancer cell
      metastasis. 

PMID- 25763875
TI  - Invasive cancer incidence and survival--United States, 2011.
AB  - Because of improvements in early detection and treatment of cancer, the
      proportion of persons with cancer who survive >=5 years after diagnosis has
      increased. To assess progress toward achieving Healthy People 2020 objectives,*
      CDC analyzed data from U.S. Cancer Statistics (USCS) for 2011, the most recent
      data available. USCS includes incidence and survival data from CDC's National
      Program of Cancer Registries (NPCR) and the National Cancer Institute's
      Surveillance, Epidemiology, and End Results (SEER) program and mortality data
      from the National Vital Statistics System. In 2011, a total of 1,532,066 invasive
      cancers were reported to cancer registries in the United States (excluding
      Nevada), for an annual incidence rate of 451 cases per 100,000 persons. Cancer
      incidence rates were higher among males (508) than females (410), highest among
      black persons (458), and ranged by state, from 374 to 509 per 100,000 persons
      (339 in Puerto Rico). The proportion of persons with cancer who survived >=5
      years after diagnosis was 65% and was similar among males (65%) and females (65%)
      but lower among black persons (60%) compared with white persons (65%).
      Surveillance of cancer incidence and survival are essential for identifying
      population groups with high cancer incidence rates and low cancer survival rates
      as well as for estimating the number of cancer survivors, which was 13.7 million
      in 2012. These data are being used by states to effectively develop comprehensive
      cancer control programs, including supporting the needs of cancer survivors. 

PMID- 25763876
TI  - Missed opportunities for tetanus postexposure prophylaxis--California, January
      2008-March 2014.
AB  - Tetanus is an acute and sometimes fatal disease characterized by sudden muscle
      contractions. The number of tetanus cases reported annually in the United States
      has declined significantly since the 1930s and 1940s as a result of the
      introduction of tetanus vaccines. However, sporadic cases continue to occur in
      persons who are not up-to-date with tetanus toxoid-containing vaccinations (TT)
      and do not receive appropriate postexposure prophylaxis (PEP). To assess the
      extent of these cases, the California Department of Public Health reviewed all
      tetanus cases reported during January 2008-March 2014. A total of 21 tetanus
      patients were reported; five (24%) died. An average of three cases were reported
      each year during 2008-2013; the average annual incidence among patients aged >=65
      years (0.23 cases per 1 million population) was twice that among patients aged 21
      64 years (0.10 cases per 1 million population). Of 16 patients with an acute
      injury before illness and diagnosis, nine (56%) sought medical care, and two
      (22%) of the nine received appropriate PEP. Although tetanus is rare, it is a
      life-threatening disease that is preventable. Health care providers should ensure
      that their patients are up-to-date with TT vaccination and provide appropriate
      postexposure prophylaxis for patients with wounds. 

PMID- 25763877
TI  - Stressful life events experienced by women in the year before their infants'
      births--United States, 2000-2010.
AB  - Epidemiologic studies suggest that prenatal stress is associated with preterm
      birth, low birth weight, and peripartum anxiety and depressive symptoms. The most
      recent population-based study, assessing trends in stress experienced in the year
      before an infant's birth, used 1990-1995 data from 11 states participating in the
      Pregnancy Risk Assessment Monitoring System (PRAMS). That study found that 64% of
      women surveyed reported experiencing at least one stressful life event (SLE),
      although the prevalence declined slightly over the study period. PRAMS data for
      2000-2010 were used to examine more recent trends and to determine if the
      prevalence of SLEs has continued to decrease in the past decade. Additionally,
      2010 data were used to determine the extent that maternal demographics and state
      of residence are associated with SLEs. This report describes the results of those
      analyses, which found that most women in the sample reported experiencing >=1
      SLEs in the year before their infant's birth, although the prevalence of
      experiencing SLEs decreased during 2000-2010. In 2010, based on data from 27
      states, 70.2% of women reported >=1 SLEs. The mean number of SLEs was 1.81,
      ranging from 1.41 in New York City to 2.26 in Oklahoma. SLEs were most frequently
      financial. Prevalence of SLEs varied by PRAMS reporting site and maternal
      demographics. Younger, less educated, unmarried, and Medicaid-covered women had
      the highest prevalence of SLEs. Public health practitioners and clinicians can
      use the information on trends and risk factors for SLEs to determine the
      likelihood that pregnant women might benefit from screening for stressors during
      pregnancy. 

PMID- 25763878
TI  - Bacterial enteric infections detected by culture-independent diagnostic tests-
      FoodNet, United States, 2012-2014.
AB  - The increased availability and rapid adoption of culture-independent diagnostic
      tests (CIDTs) is moving clinical detection of bacterial enteric infections away
      from culture-based methods. These new tests do not yield isolates that are
      currently needed for further tests to distinguish among strains or subtypes of
      Salmonella, Campylobacter, Shiga toxin-producing Escherichia coli, and other
      organisms. Public health surveillance relies on this detailed characterization of
      isolates to monitor trends and rapidly detect outbreaks; consequently, the
      increased use of CIDTs makes prevention and control of these infections more
      difficult. During 2012-2013, the Foodborne Diseases Active Surveillance Network
      (FoodNet*) identified a total of 38,666 culture-confirmed cases and positive CIDT
      reports of Campylobacter, Salmonella, Shigella, Shiga toxin-producing E. coli,
      Vibrio, and Yersinia. Among the 5,614 positive CIDT reports, 2,595 (46%) were not
      confirmed by culture. In addition, a 2014 survey of clinical laboratories serving
      the FoodNet surveillance area indicated that use of CIDTs by the laboratories
      varied by pathogen; only CIDT methods were used most often for detection of
      Campylobacter (10%) and STEC (19%). Maintaining surveillance of bacterial enteric
      infections in this period of transition will require enhanced surveillance
      methods and strategies for obtaining bacterial isolates. 

PMID- 25763879
TI  - Notes from the field: multistate outbreak of human salmonella infections linked
      to live poultry from a mail-order hatchery in Ohio--February-October 2014.
AB  - In early 2014, five clusters of human Salmonella infections were identified
      through PulseNet, the national molecular subtyping network for foodborne disease
      surveillance. Many ill persons in each of these clusters reported contact with
      live poultry, primarily chicks and ducklings, from a single mail-order hatchery;
      therefore, the clusters were merged into a single investigation. During February
      3-October 14, 2014, a total of 363 persons infected with outbreak strains of
      Salmonella serotypes Infantis, Newport, and Hadar were reported from 43 states
      and Puerto Rico, making it the largest live poultry-associated salmonellosis
      outbreak reported in the United States. 

PMID- 25763881
TI  - N-glycome profiling of patatins from different potato species of Solanum genus.
AB  - It is hypothesized that oligosaccharides are another potential source of
      immunological cross-reaction between different plant allergens. Patatin is the
      most abundant glycoprotein in potato and has been described to have an
      oligosaccharide of composition Man3(Xyl)GlcNAc2(Fuc). In this work, N
      glycosylation profiles of patatin proteins isolated from tubers of different
      potato species were investigated and compared. Oligosaccharides were released by
      enzymatic digestion with PNAGase A and analyzed primarily by matrix-assisted
      laser desorption ionization mass spectrometry. For glycan labeling, a modified
      version of on-target derivatization with phenylhydrazine was applied. This study
      found the presence of glycan structures not described previously in patatins of
      potato tubers, and their glycan profiles significantly differed. This knowledge
      about the glycosylation of potato patatins may be helpful for correct choice of
      potato species to decrease the presence of specific glycan epitopes causing food
      allergy as well as for utilization of potatoes for the manufacture of therapeutic
      proteins.

PMID- 25763880
TI  - A prime/boost strategy using DNA/fowlpox recombinants expressing the genetically
      attenuated E6 protein as a putative vaccine against HPV-16-associated cancers.
AB  - BACKGROUND: Considering the high number of new cases of cervical cancer each year
      that are caused by human papilloma viruses (HPVs), the development of an
      effective vaccine for prevention and therapy of HPV-associated cancers, and in
      particular against the high-risk HPV-16 genotype, remains a priority. Vaccines
      expressing the E6 and E7 proteins that are detectable in all HPV-positive pre
      cancerous and cancer cells might support the treatment of HPV-related lesions and
      clear already established tumors. METHODS: In this study, DNA and fowlpox virus
      recombinants expressing the E6F47R mutant of the HPV-16 E6 oncoprotein were
      generated, and their correct expression verified by RT-PCR, Western blotting and
      immunofluorescence. Immunization protocols were tested in a preventive or
      therapeutic pre-clinical mouse model of HPV-16 tumorigenicity using heterologous
      (DNA/FP) or homologous (DNA/DNA and FP/FP) prime/boost regimens. The immune
      responses and therapeutic efficacy were evaluated by ELISA, ELISPOT assays, and
      challenge with TC-1* cells. RESULTS: In the preventive protocol, while an anti-E6
      specific humoral response was just detectable, a specific CD8(+) cytotoxic T-cell
      response was elicited in immunized mice. After the challenge, there was a delay
      in cancer appearance and a significant reduction of tumor volume in the two
      groups of E6-immunized mice, thus confirming the pivotal role of the CD8(+) T
      cell response in the control of tumor growth in the absence of E6-specific
      antibodies. In the therapeutic protocol, in-vivo experiments resulted in a higher
      number of tumor-free mice after the homologous DNA/DNA or heterologous DNA/FP
      immunization. CONCLUSIONS: These data establish a preliminary indication for the
      prevention and treatment of HPV-related tumors by the use of DNA and avipox
      constructs as safe and effective immunogens following a prime/boost strategy. The
      combined use of recombinants expressing both E6 and E7 proteins might improve the
      antitumor efficacy, and should represent an important approach to control HPV
      associated cancers.

PMID- 25763882
TI  - Proteo-lipobeads for the oriented encapsulation of membrane proteins.
AB  - As a surrogate of live cells, proteo-lipobeads are presented, encapsulating
      functional membrane proteins in a strict orientation into a lipid bilayer. Assays
      can be performed just as on live cells, for example using fluorescence
      measurements. As a proof of concept, we have demonstrated proton transport
      through cytochrome c oxidase. 

PMID- 25763884
TI  - Corrigendum: peripheral blood miRNAs as a biomarker for chronic cardiovascular
      diseases.

PMID- 25763883
TI  - Water-compatible molecularly imprinted polymer as a sorbent for the selective
      extraction and purification of adefovir from human serum and urine.
AB  - A molecularly imprinted polymer has been synthesized to specifically extract
      adefovir, an antiviral drug, from serum and urine by dispersive solid-phase
      extraction before high-performance liquid chromatography with UV analysis. The
      imprinted polymers were prepared by bulk polymerization by a noncovalent
      imprinting method that involved the use of adefovir (template molecule) and
      functional monomer (methacrylic acid) complex prior to polymerization, ethylene
      glycol dimethacrylate as cross-linker, and chloroform as porogen. Molecular
      recognition properties, binding capacity, and selectivity of the molecularly
      imprinted polymers were evaluated and the results show that the obtained polymers
      have high specific retention and enrichment for adefovir in aqueous medium. The
      new imprinted polymer was utilized as a molecular sorbent for the separation of
      adefovir from human serum and urine. The serum and urine extraction of adefovir
      by the molecularly imprinted polymer followed by high-performance liquid
      chromatography showed a linear calibration curve in the range of 20-100 MUg/L
      with excellent precisions (2.5 and 2.8% for 50 MUg/L), respectively. The limit of
      detection and limit of quantization were determined in serum (7.62 and 15.1
      MUg/L), and urine (5.45 and 16 MUg/L). The recoveries for serum and urine samples
      were found to be 88.2-93.5 and 84.3-90.2%, respectively. 

PMID- 25763885
TI  - Correlation between the Wells score and the Quanadli index in patients with
      pulmonary embolism.
AB  - BACKGROUND AND AIMS: Determining clinical probability of pulmonary embolism (PE)
      with Wells scoring system is the first step towards diagnosis of PE. Definitive
      diagnosis of PE is confirmed by computed tomography pulmonary angiography (CTPA).
      METHODS: This was a prospective study on 80 patients referred to the Institute
      for Pulmonary Diseases of Vojvodina with suspected PE between April 2010 and
      August 2012. Clinical probability of PE was determined according to the Wells and
      modified Wells scoring system. CTPA was performed in 60 patients. The degree of
      pulmonary vascular obstruction was quantified by the Qanadli index. RESULTS: Low
      clinical probability of PE was present in one patient (1.6%), moderate in 43
      (71.6%) and high in 16 (26.6%) patients. PE was confirmed in 50 (83.3%) patients.
      There were 21 patients (42%) whose Quanadli index was <25%, 18 (36%) between 25%
      50%, while Quanadli index was >=50 in 11 patients (22%). When compared to CTPA
      findings, modified Wells scoring system showed 90% sensitivity [95% confidence
      interval (CI) 78.2%-96.6%], and 20% specificity (95% CI 3.11%-55.6%), positive
      predictive value (PPV) 84.9% (95% CI 72.4%-93.2%) and negative predictive value
      (NPV) 28.6% (95% CI 4.5%-70.7%). There was weak positive correlation between
      Wells score and Quanadli index (r = 0.14; P = 0.29), without statistical
      significance. Wells score was significantly higher in haemodynamically unstable
      than in haemodynamically stable patients (6.8 vs 5.6, P = 0.014). There was no
      statistically significant difference between the values of Quanadli index in
      these two groups (31.33% vs 26.64%, P = 0.062). CONCLUSION: Modified Wells
      criteria have high sensitivity but low specificity in PE diagnostics. The Wells
      score does not correlate well with the Quanadli index.

PMID- 25763886
TI  - Considering cognition. Current challenges and future directions in pulmonary and
      critical care fellowship training.
AB  - Fellowship training in pulmonary and critical care has evolved substantially over
      the past decade. Training programs are increasingly focused on a rigorous,
      multifaceted assessment of an individual trainee's progress toward achieving
      specific curricular milestones, and their ability to independently manage a
      series of entrustable professional activities. This new system has provided
      programs with an enormous amount of detailed information related to the specific
      goals and outcomes of training. However, it has not addressed the unmet need for
      fellowship programs to systematically assess and teach advanced clinical
      reasoning and judgment. Training programs must address these cognitive processes
      in a proactive and supportive way, and are challenged to develop novel approaches
      that encourage continuous self-evaluation. Only by addressing these critical
      deficiencies will programs enable trainees to progress beyond a level of clinical
      competence to one of true expertise. These efforts will also encourage physicians
      at all levels of training to embrace their commitment to lifelong learning. 

PMID- 25763887
TI  - Proximal weakness in a patient with MALT lymphoma: a case report and discussion
      of possible pathogenesis.

PMID- 25763890
TI  - Structural and volumetric changes in the aging face.
AB  - Traditional views on facial aging and associated therapies focused on soft tissue
      descent and skin texture changes. Recently, revolumization for age-related
      lipoatrophy has become increasingly popular. Researchers are now reporting
      objective studies examining processes of structural and volumetric changes with
      age in increasing frequency as well. To better understand and treat facial aging,
      the surgeon should review all available data. Presented here are current evidence
      based studies regarding age-related changes in the facial skeleton and soft
      tissue envelope. By reviewing these changes by each anatomic subsite, the surgeon
      will be better equipped to develop an appropriate treatment plan, individualized
      for each patient. 

PMID- 25763888
TI  - Tailoring cyanine dark states for improved optically modulated fluorescence
      recovery.
AB  - Cyanine dyes are well-known for their bright fluorescence and utility in
      biological imaging. However, cyanines also readily photoisomerize to produce
      nonemissive dark states. Co-illumination with a secondary, red-shifted light
      source on-resonance with the longer wavelength absorbing dark state reverses the
      photoisomerization and returns the cyanine dye to the fluorescent manifold,
      increasing steady-state fluorescence intensity. Modulation of this secondary
      light source dynamically alters emission intensity, drastically improving
      detection sensitivity and facilitating fluorescence signals to be recovered from
      an otherwise overwhelming background. Red and near-IR emitting cyanine
      derivatives have been synthesized with varying alkyl chain lengths and halogen
      substituents to alter dual-laser fluorescence enhancement. Photophysical
      properties and enhancement with dual laser modulation were coupled with density
      functional calculations to characterize substituent effects on dark state
      photophysics, potentially improving detection in high background biological
      environments. 

PMID- 25763891
TI  - Introduction to volumetric facial rejuvenation.
AB  - The volumetric techniques of injectable fillers and autologous fat transfer are
      an important tool in the treatment of facial aging. Rapid widespread adoption has
      outpaced a sophisticated understanding of the goals of volume rejuvenation. The
      development of shadows and shadow patterns are the fundamental changes that occur
      with volumetric facial aging. A detailed examination of these shadows will lead
      to an understanding of how to apply volumetric techniques to create natural
      appearing results. 

PMID- 25763892
TI  - Volumetric rejuvenation: general concepts.
AB  - Volume restoration has become a cornerstone in facial rejuvenation. This article
      focuses on the aesthetic concepts of volume loss and how to restore volume to
      mimic nature. The concept of evolving facial shape from a circle, to an upright
      triangle, to a square, to an inverted triangle is covered. Little model of the
      inverted egg shape is also proposed. The benefit of restoring an outer facial
      frame, periorbital frame, and perioral frame is elaborated. Lip volumization is
      also briefly covered. Finally, understanding the role of highlights and shadows
      on the impact of aging is addressed. 

PMID- 25763893
TI  - Fat transfer techniques: general concepts.
AB  - Facial volume loss has become widely accepted as one of the contributing factors
      in global facial aging. Some have even suggested that bony, muscular, fatty, and
      dermal/epidermal changes are more integral in the aging process than
      gravitational influence. Although detractors of autologous fat transfer persist,
      facial autologous fat transfer has become widely utilized as one option for
      volume restoration. Various techniques in harvesting, processing, and injecting
      autologous fat have been debated at length without clear guidelines emerging to
      maximize outcomes. This article aims to present one surgeon's experience in
      successful fat grafting philosophy and technique. Areas covered will include
      preparation, harvesting, processing, and injection techniques. The injection
      techniques are organized by facial region and into the general philosophy and
      thinking regarding the facial region as well as the specific technique that has
      been utilized over 7 years and hundreds of successful procedures. 

PMID- 25763894
TI  - Injectable fillers: review of material and properties.
AB  - With an increasing understanding of the aging process and the rapidly growing
      interest in minimally invasive treatments, injectable facial fillers have changed
      the perspective for the treatment and rejuvenation of the aging face. Other than
      autologous fat and certain preformed implants, the collagen family products were
      the only Food and Drug Administration approved soft tissue fillers. But the
      overwhelming interest in soft tissue fillers had led to the increase in research
      and development of other products including bioengineered nonpermanent implants
      and permanent alloplastic implants. As multiple injectable soft tissue fillers
      and biostimulators are continuously becoming available, it is important to
      understand the biophysical properties inherent in each, as these constitute the
      clinical characteristics of the product. This article will review the materials
      and properties of the currently available soft tissue fillers: hyaluronic acid,
      calcium hydroxylapatite, poly-l-lactic acid, polymethylmethacrylate, and
      autologous fat (and aspirated tissue including stem cells). 

PMID- 25763895
TI  - Integrating injectable fillers and fat in facial rejuvenation.
AB  - This article focuses on the discussion of the risks, benefits, and limitations of
      the three principal methods for facial volumization: fat grafting, injectable
      fillers, and alloplastic implants. By understanding these issues, a surgeon can
      better discuss what would be ideal for a particular patient. Fat grafting offers,
      the most cost-effective solution to a patient with sufficient volume loss.
      Injectable fillers provide an easy, predictable, and accurate nonsurgical
      alternative that is scalable in cost. Alloplastic implants are more ideally used
      in individuals with skeletal rather than soft-tissue deficiencies or in younger
      patients where the soft-tissue envelope is sufficient to mask the implant. 

PMID- 25763896
TI  - Volume rejuvenation of the facial upper third.
AB  - The next three articles in this issue take a unique approach to discussing
      volumetric restoration. Robert Glasgold has provided an assessment for each
      facial region and five different renowned authors (TK, SPS, RF, SML, and EFW)
      have been asked to speak on a particular volumetric product, of which they are
      considered an expert, as it applies to the different regions of the face. The
      articles are broken into the following: (1) upper third which corresponds to the
      upper eyelid, brow, temple, and forehead; (2) middle third which will cover lower
      eyelid, cheek, and perioral area; and (3) lower third which discusses the
      marionette, prejowl, and jawline. Our hope is that by placing differing opinions
      of experienced authors, organized by facial region together, the reader will have
      the opportunity to more readily compare the options. The contributing authors and
      their product area are as follows: Theda Kontis, MD-hyaluronic acid; Steve Smith,
      MD-calcium hydroxyl appetite; Rebecca Fitzgerald, MD-poly-L lactic acid; Sam Lam,
      MD-polymethyl methacrylate; and Edwin Williams, MD-Autologous Fat Transfer. If
      the author included general comments on the product, they are included in the
      article on the upper face only and are not repeated. Please note that other
      individuals may also have significantly assisted in the production of these
      articles, but those listed above are the senior authors. 

PMID- 25763897
TI  - Volume management of the middle third-lower orbit/midface.
AB  - This is the second of the three articles discussing volumetric rejuvenation of
      the face. The previous article, Volume Rejuvenation of the Facial Upper Third,
      focused on the upper one-third of the face while this article focuses on the
      middle one-third, primarily the lower eyelid, cheek, and perioral area. Again,
      the authors (RG, TK, SPS, RF, SL, and EFW) from the upper face article have
      provided a summary of rejuvenation utilizing a product of which they are
      considered an expert. Robert Glasgold has provided volumetric analysis of the
      region as an introduction. 

PMID- 25763898
TI  - Volume rejuvenation of the lower third, perioral, and jawline.
AB  - This is the third and final article discussing volumetric rejuvenation of the
      face. The previous two articles, Rejuvenation of the Upper Third and Management
      of the Middle Third, focused on the upper two-thirds of the face while this
      article focuses on the lower face, including the marionette area, jawline, and
      neck. Again, the authors of the previous two articles have provided a summary of
      rejuvenation utilizing a product of which they are considered an expert. Robert
      Glasgold has provided volumetric analysis of the region as an introduction. 

PMID- 25763899
TI  - Illusion of volume loss.
AB  - Facial aging can create an appearance of volume loss and responds to volume
      enhancement in certain clinical scenarios. Actual fat loss is an illusion created
      by the inter-relationship of the different tissue types. The purpose of this
      article is to provide the anatomical, clinical, and research evidence to
      differentiate the contributions to facial aging from gravity's effects on soft
      tissue, fat loss, and skeletal remodeling, explaining the illusion. 

PMID- 25763900
TI  - A huge cutaneous horn of ear.
AB  - A rare case of huge cutaneous horn of the ear was presented. The lesion was
      totally excised over the auricular cartilage with a 5-mm margin and the defect
      was closed with a full-thickness skin graft taken from the preauricular area. To
      the best of our knowledge, there is no any report of this kind of interesting
      cutaneous corn of the ear. 

PMID- 25763901
TI  - A systematic review of community pharmacist therapeutic knowledge of dietary
      supplements.
AB  - BACKGROUND: Internationally, the use of dietary supplements has been growing
      rapidly. Patient support for pharmacist sales of nutritional and dietary
      supplements is also strong. The increase in demand for nutritional and dietary
      supplements and subsequent advice about these products, however, makes it
      necessary that pharmacists maintain a contemporary knowledge of the area. AIM OF
      REVIEW: This systematic review was conducted to examine the current evidence
      regarding the level of the nutritional and dietary supplement knowledge of
      community pharmacists and their understanding of their therapeutic effects.
      METHOD: Electronic databases including Medline, Scopus, Embase, CINAHL, Scifinder
      and the Cochrane Controlled Trials Register were searched. Studies assessing
      nutritional knowledge of pharmacists in community pharmacies were eligible for
      inclusion. All languages and study designs were considered. Study results were
      analysed and pharmacist knowledge scores were given out of 100 %. Results From
      5594 studies identified, nine met the inclusion criteria. Each study tested
      pharmacist knowledge with predetermined questions calculating results as the
      number of questions answered correctly. These knowledge scores were converted to
      a percentage score for the purpose of this paper. The median knowledge score
      across all papers was 64 %. A lack of studies assessing community pharmacists'
      knowledge of commonly sold vitamins and minerals was observed. CONCLUSIONS:
      Global community pharmacist knowledge of dietary supplements appears to be poor.
      Community pharmacists have an professional responsibility to provide accurate
      health information about dietary supplements as they do for any other therapies
      they provide to patients. Further research including that which assesses
      pharmacists' therapeutic knowledge of commonly sold vitamins and minerals is
      suggested.

PMID- 25763902
TI  - Genome-wide association study and meta-analysis identify ISL1 as genome-wide
      significant susceptibility gene for bladder exstrophy.
AB  - The bladder exstrophy-epispadias complex (BEEC) represents the severe end of the
      uro-rectal malformation spectrum, and is thought to result from aberrant
      embryonic morphogenesis of the cloacal membrane and the urorectal septum. The
      most common form of BEEC is isolated classic bladder exstrophy (CBE). To identify
      susceptibility loci for CBE, we performed a genome-wide association study (GWAS)
      of 110 CBE patients and 1,177 controls of European origin. Here, an association
      was found with a region of approximately 220kb on chromosome 5q11.1. This region
      harbors the ISL1 (ISL LIM homeobox 1) gene. Multiple markers in this region
      showed evidence for association with CBE, including 84 markers with genome-wide
      significance. We then performed a meta-analysis using data from a previous GWAS
      by our group of 98 CBE patients and 526 controls of European origin. This meta
      analysis also implicated the 5q11.1 locus in CBE risk. A total of 138 markers at
      this locus reached genome-wide significance in the meta-analysis, and the most
      significant marker (rs9291768) achieved a P value of 2.13 * 10-12. No other locus
      in the meta-analysis achieved genome-wide significance. We then performed murine
      expression analyses to follow up this finding. Here, Isl1 expression was detected
      in the genital region within the critical time frame for human CBE development.
      Genital regions with Isl1 expression included the peri-cloacal mesenchyme and the
      urorectal septum. The present study identified the first genome-wide significant
      locus for CBE at chromosomal region 5q11.1, and provides strong evidence for the
      hypothesis that ISL1 is the responsible candidate gene in this region. 

PMID- 25763903
TI  - Photodegradation of Hydrophobic Pyridineketoximes in Toluene and Heptane.
AB  - The goal of the research was to study the reactivity of the hydrophobic 2- and 3
      pyridineketoximes under exposure to UV-VIS light. The photodegradation was
      conducted in both toluene and heptane for 10 h under atmosphere of argon. Ten
      hour irradiation experiments demonstrated that the pyridineketoximes underwent
      the facile E-Z photoisomerization, photo-Beckmann rearrangement, and to a lesser
      extent, the photosubstitution to the pyridine ring. From LC-MS and NMR analysis
      of the irradiated solutions, it was found that the photosubstitution proceeded to
      give the corresponding 6-substituted 2- or 3-pyridylketoxime via the replacement
      of the ring hydrogen by the benzyl or heptyl group. The photo-Beckmann
      rearrangement led to the formation of the corresponding amides, but also other
      products formed in the photo-decomposition reaction. 

PMID- 25763905
TI  - Failure pressures of three rhinologic dural repairs in a porcine ex vivo model.
AB  - BACKGROUND: The objective of this work was to determine the failure pressures of
      3 commonly performed repair techniques of 5-mm dural defects in a controlled
      setting. METHODS: This was a pig dura ex vivo study. A testing apparatus was
      fabricated to study failure pressures of 3 different repairs in a porcine model.
      Five-millimeter (5-mm) dural defects were created and plugged with autologous
      mucosa/Tisseel (MT) (Baxter International Inc.), fat graft (FG), and bath plug
      (BP) techniques. Saline solution was infused at 30 mL/hour to apply
      unidirectional pressure to the repair until failure occurred. Five dural repairs
      were performed for each arm of the trial, for a total of 15 trials. RESULTS: The
      mean failure pressure of the MT repair was 4.3 +/- 1.9 cmH2 O, of the FG repair
      was 10.9 +/- 4.2 cmH2 O, and of the BP repair was 20.7 +/- 2.2 cmH2 O.
      Differences among mean failure pressures were statistically significant.
      CONCLUSION: The BP repair showed significantly higher tolerances for pressure
      than the other 2 repairs. The BP repair was the only technique that withstood
      adult physiologic supine cerebrospinal fluid (CSF) pressure.

PMID- 25763906
TI  - Teleradiotherapy Network: Applications and Feasibility for Providing Cost
      Effective Comprehensive Radiotherapy Care in Low- and Middle-Income Group
      Countries for Cancer Patients.
AB  - Globally, new cancer cases will rise by 57% within the next two decades, with the
      majority in the low- and middle-income countries (LMICs). Consequently, a steep
      increase of about 40% in cancer deaths is expected there, mainly because of lack
      of treatment facilities, especially radiotherapy. Radiotherapy is required for
      more than 50% of patients, but the capital cost for equipment often deters
      establishment of such facilities in LMICs. Presently, of the 139 LMICs, 55 do not
      even have a radiotherapy facility, whereas the remaining 84 have a deficit of
      61.4% of their required radiotherapy units. Networking between centers could
      enhance the effectiveness and reach of existing radiotherapy in LMICs. A
      teleradiotherapy network could enable centers to share and optimally utilize
      their resources, both infrastructure and staffing. This could be in the form of a
      three-tier radiotherapy service consisting of primary, secondary, and tertiary
      radiotherapy centers interlinked through a network. The concept has been adopted
      in some LMICs and could also be used as a "service provider model," thereby
      reducing the investments to set up such a network. Teleradiotherapy networks
      could be a part of the multipronged approach to address the enormous gap in
      radiotherapy services in a cost-effective manner and to support better
      accessibility to radiotherapy facilities, especially for LMICs. 

PMID- 25763907
TI  - [New trends and novel possibilities in functional medical imaging: imaging
      methods].
AB  - The aim of the study is to review the new tomographic imaging technologies which
      enable to investigate the metabolic activity of the human body. Accordingly, we
      overview the current promising methodology in the field of PET and SPECT, but we
      will also mention interesting applications at the area of MRI and CT. 

PMID- 25763908
TI  - [New trends and novel possibilities in the management of oncologic patients:
      clinical uses of PET/MRI].
AB  - The most recent multimodality technique, the hybrid positron emission
      tomography/magnetic resonance imaging (PET/MRI) combines two very different
      technologies, which is a great result of human creativity. The combined PET/MRI
      has significant potentials in clinical oncology providing new perspectives of
      functional and anatomical information. PET/MRI offers simultaneous measurements
      of multifunctional data such as PET mapping by different specific tracers or MRI
      morphologic, MR molecular (MR spectroscopy, MRS), or MR functional (fMR)
      information of a living system. 

PMID- 25763909
TI  - [New trends and novel possibilities in the clinical use of SPECT/CT imaging].
AB  - The application of hybrid equipments and fused techniques has increasing
      importance in the field of imaging diagnostics. The biggest advantage of these
      methods is the simultaneous use of several modalities which can give data about
      the morphological, functional as well as molecular changes of the different
      diseases at the same time. The facilities, advantages and the applicability of
      the SPECT/CT (single photon emission computer tomograph/computer tomograph) are
      summarized in this paper mainly in oncologic diseases, but also in other
      disorders. The multimodality equipments showing the function and morphology
      together increase the specificity and diagnostic accuracy of the nuclear medicine
      methods and were found to be more efficient in the therapy effectiveness, too.

PMID- 25763910
TI  - [11C-choline PET/CT in the diagnosis of prostate cancer -- Hungarian experience].
AB  - 11C-choline has been used in the diagnosis and follow-up of patients with
      prostate cancer for years. Choline PET/CT has been available in human care since
      March, 2014 in our country. Unfortunately this examination has not been
      reimbursed by the National Health Insurance so far. We retrospectively analysed
      and assessed the results of 40 patients who underwent 11C-choline PET/CT on the
      basis of previous literature. As our study group was heterogeneous statistical
      analysis was not performed. 

PMID- 25763911
TI  - [Modern imaging of liver and pancreatic neoplasms].
AB  - Modern imaging modalities play an outstanding role in the detection,
      characterization, staging, therapy planning, treatment outcome evaluation and
      follow-up of patients with liver and pancreatic neoplasms. Diagnostic performance
      and accuracy of the available modalities are continuously improving therefore, it
      is necessary to overview from time to time the diagnostic protocols and
      algorithms. 

PMID- 25763912
TI  - [New trends and novel possibilities in the radiodiagnosis of lung cancer].
AB  - In recent years there have been significant changes in the management of lung
      cancer. In 2009 a new staging system became effective while in 2011 a new
      adenocarcinoma classification was introduced. Molecular biology, genetics with
      hybrid multimodal imaging progressed greatly. New biopsy needles were developed
      for the histological analysis in molecular pathology. Role of LDCT screening in
      early diagnosis of lung cancer became evident and working groups put it into
      practice. Integrated and multiparametric devices facilitate more accurate patient
      follow-up with new biomarkers and newly developed contrast materials. The future
      of radiology is in the combined use of anatomical, functional and molecular
      medical imaging. 

PMID- 25763913
TI  - [New trends and novel possibilities in the diagnostic imaging of breast cancer].
AB  - Complex tumor therapy development and new opportunities in surgery, which take
      into account both oncological principles as well as esthetic aspects, have set
      the requirements far higher for diagnostic imaging of the breast and for
      radiologists. Despite these new opportunities, X-ray mammography remains the
      basic examination. However, part of the cancers is hidden on the mammogram, which
      is partly a consequence of the dense glandular tissue and may also be influenced
      by the histological type of cancer. Besides reducing radiation dose, digital X
      ray mammography improves the examination sensitivity of the dense breast. State
      of the art digital examination methods, such as tomosynthesis and contrast
      enhanced mammography, increase the accuracy of examination. Ultrasound
      mammography is the most important supplementary method of X-ray mammography.
      Among the new applications of ultrasound mammography, US elastography, which is
      based on different tissue elasticity, as well as automatic 3D ultrasound, can be
      highlighted. Furthermore, among imaging methods that provide functional or
      metabolic data, MR mammography is the most appropriate non-invasive, non-ionising
      method for the detection of malignancy and for structure examination. MR
      mammography is the most sensitive method for the detection of breast cancer and
      in 20-30% of cases, results in changes of the therapy, and it is also effective
      in the examination of the dense breast. High level of evidence proves that MR
      mammography is very useful in the screening of women at risk of breast cancer.
      Promising results prove that MR mammography will play more considerable role in
      the evaluation of the effectiveness of the therapy. Diffusion-weighted MR imaging
      is based on the different diffusion of tissue water, qualitative analysis and
      quantitative evaluation can be performed. DCE-MR examines that contrast
      enhancement over time, which can mainly be useful for the qualitative and
      quantitative evaluation of perfusion changes which may indicate the biological
      response to tumor therapy. The MR spectroscopic (MRSI) biochemical analysis
      increases the characterization of the lesions. Multimodal imaging techniques
      provide more accurate analysis, which is confirmed by more and more evidence, but
      none of the imaging methods are sufficiently specific to provide histological
      diagnosis. However, imaging-guided biopsies enable precise histological or
      cytological confirmation. Technical development, new imaging methods, experienced
      radiologists and multi-disciplinary cooperation increase the accuracy of the
      diagnosis and the effectiveness of personalized therapy.

PMID- 25763914
TI  - [New trends and novel possibilities in the diagnosis of esophageal tumors].
AB  - The diagnosis of esophageal malignancies remains to be a significant challenge.
      The lack of symptoms and widely applicable, predictive screening tests make their
      early recognition difficult, however this would be essential for the successful
      treatment, cost-effective management and the improvement of survival. In this
      manuscript the author discusses the diagnostic tools available at present and in
      the near future.

PMID- 25763915
TI  - [New trends and novel possibilities in the endoscopic diagnostics of
      gastrointestinal tumors].
AB  - This publication shortly reviews the attributes of cornerstones of the latest
      technical developments in the field of endoscopy (virtual chromoendoscopy,
      optical biopsy, etc.), as well as some technical details of novel endoscopic
      methods (deep enteroscopy, capsule endoscopy). It evaluates the clinical
      consequences of the technical progress concerning several diseases that are
      important from the point of view of oncology. Some novel endoscopic innovations
      till now with uncertain clinical relevance are also mentioned. We can face the
      fact what a huge gap exists between our everyday possibilities at almost all our
      workplaces and the up-to-date endoscopic diagnostic modalities of the developed
      world. 

PMID- 25763916
TI  - [Advancements in the diagnosis of melanoma].
AB  - The continuously increasing incidence of melanoma and new developments in the
      therapy of metastatic disease require accurate diagnosis in all stages of
      melanoma. This study overviews the development of diagnostics tools in recent
      years/decades that are used in everyday medical practice such as optical
      diagnostic tools utilized for diagnosing primary tumors, sentinel lymph node
      biopsy, developments in molecular diagnostics, as well as the role of PET/CT in
      imaging techniques. 

PMID- 25763917
TI  - [New trends and novel possibilities in the diagnosis of lymphomas].
AB  - Successful treatment of lymphomas requires classical morphological diagnosis and
      also immunophenotyping as well as cytogenetics and molecular genetic
      examinations. The expansion of pathogenetic knowledge resulted in new
      classifications, new disease entities, and subtypes that are identified with
      distinct genetic aberrations bearing prognostic value as well and also serving as
      potential targets for new targeted therapies. The more detailed molecular
      background is explored the more precise personalized treatment options can be
      utilized nowadays and in the near future. Thus new up-to-date hematopathology is
      the key to successful oncohematological treatment. The imaging diagnosis has also
      evolved during the last decade in the diagnosis of lymphomas. This can also help
      us to monitor response to therapy by using positron emission tomography. This
      enables us to monitor therapy and make decisions based on efficiency of the
      therapeutic regimen. Survival data of lymphoma patients can further be improved
      by avoiding under- and overtreatment, which is achieved by using PET/CT as a
      "biomarker" or response indicator besides conventional biologic and clinical
      prognostic markers. 

PMID- 25763918
TI  - Radiographic angles in hallux valgus: Comparison between protractor and iPhone
      measurements.
AB  - Radiographic angles are used to assess the severity of hallux valgus deformity,
      make preoperative plans, evaluate outcomes after surgery, and compare results
      between different methods. Traditionally, hallux valgus angle (HVA) has been
      measured by using a protractor and a marker pen with hardcopy radiographs. The
      main objective of this study is to compare HVA measurements performed using a
      smartphone and a traditional protractor. The secondary objective was to compare
      the time taken between those two methods. Six observers measured major HVA on 20
      radiographs of hallux valgus deformity with both a standard protractor and an
      Apple iPhone. Four of the observers repeated the measurements at least a week
      after the original measurements. The mean absolute difference between pairs of
      protractor and smartphone measurements was 3.2 degrees . The 95% confidence
      intervals for intra-observer variability were +/-3.1 degrees  for the smartphone
      measurement and +/-3.2 degrees  for the protractor method. The 95% confidence
      intervals for inter-observer variability were +/-9.1 degrees  for the smartphone
      measurement and +/-9.6 degrees  for the protractor measurement. We conclude that
      the smartphone is equivalent to the protractor for the accuracy of HVA
      measurement. But, the time taken in smartphone measurement was also reduced.

PMID- 25763919
TI  - Hydride-induced anionic cyclization: an efficient method for the synthesis of 6-H
      phenanthridines via a transition-metal-free process.
AB  - A novel procedure for hydride-induced anionic cyclization has been developed. It
      includes the reduction of a biaryl bromo-nitrile with a nucleophilic aromatic
      substitution (S(N)Ar). A range of polysubstituted 6-H-phenanthridines were so
      obtained in moderate to good yield with good substrate tolerance. This method
      involves a concise transition-metal-free process and was applied to synthesize
      natural alkaloids.

PMID- 25763920
TI  - Exposure to increased levels of estradiol during development can have long-term
      effects on the response to undernutrition in female rats.
AB  - OBJECTIVES: Undernutrition during development alters the expression of peptides
      that control energy expenditure and feeding behavior. Estrogens can also modulate
      these peptides. Here, we analyze whether the early postnatal administration of
      estradiol modulates the effects of undernutrition on neuroendocrine parameters in
      adult female Wistar rats. METHODS: Control rats were fed a control diet.
      Undernourished pups were submitted to a restricted diet with half of the
      undernourished rats receiving 0.4 mg/kg s.c. of estradiol benzoate (EB) from
      postnatal day (P) 6 until P13. Quantitative real-time polymerase chain reaction
      was performed to determine expression in the hypothalamus of agouti-related
      peptide (AgRP), proopiomelanocortin (POMC), neuropeptide Y (NPY), and cocaine-
      and amphetamine-regulated transcript. Plasma estradiol, testosterone, and
      adiponectin levels were measured by enzyme-linked immunosorbent assay. Total and
      acylated ghrelin levels were measured in plasma by radioimmunoassay. Insulin and
      leptin were measured by mulitplex immunoassays. RESULTS: Undernourishment
      decreased body weight, fat mass, plasma leptin and insulin levels, and
      hypothalamic POMC mRNA levels. An increase in orexigenic signals AgRP and NPY
      mRNA levels, and in plasma adiponectin levels were found in undernourished
      animals. Early postnatal treatment with EB to undernourished female rats reversed
      the effects of undernutrition on adult hypothalamic POMC mRNA levels. In
      addition, neonatal EB treatment to undernourished females significantly decreased
      adult plasma testosterone, estradiol, and acylated ghrelin levels. DISCUSSION:
      Our results suggest that increased estradiol during a critical period of
      development has the capacity to modulate the alterations that undernutrition
      produces on energy metabolism.

PMID- 25763921
TI  - Effect of 6 Months of Balance Training During Pulmonary Rehabilitation in
      Patients With COPD.
AB  - PURPOSE: Balance impairment is recognized as an important issue for patients with
      chronic obstructive pulmonary disease (COPD). The aim of this study was to
      examine the effect of balance training as part of pulmonary rehabilitation (PR)
      on balance in COPD patients. METHODS: Patients were randomly assigned to an
      intervention or usual care group. The intervention group underwent balance
      training 3 times a week for 6 months in addition to the standard PR. The control
      group received 6 months of the standard PR program only. Balance was assessed by
      the Timed Up and Go (TUG), Tinetti, Berg Balance Scale (BBS), and the Unipodal
      Stance (UST) tests. Balance confidence was rated using the ABC scale. Exercise
      tolerance was determined using a 6-Minute Walk Test. RESULTS: Following the
      completion of PR, the intervention group showed improvement in all balance
      measures. Only TUG, ABC, and UST scores were improved in the usual care group (P
      < .05). Results demonstrated significant between-group differences in TUG,
      Tinetti, BBS, and ABC scores (P < .01) and UST score (P < .05). CONCLUSIONS:
      Balance training incorporated into a standard PR program significantly improves
      scores on balance tests in COPD patients.

PMID- 25763922
TI  - Participation Rates, Process Monitoring, and Quality Improvement Among Cardiac
      Rehabilitation Programs in the United States: A NATIONAL SURVEY.
AB  - PURPOSE: Although strategies exist for improving cardiac rehabilitation (CR)
      participation rates, it is unclear how frequently these strategies are used and
      what efforts are being made by CR programs to improve participation rates.
      METHODS: We surveyed all CR program directors in the American Association of
      Cardiovascular and Pulmonary Rehabilitation's database. Data collection included
      program characteristics, the use of specific referral and recruitment strategies,
      and self-reported program participation rates. RESULTS: Between 2007 and 2012,
      49% of programs measured referral of inpatients from the hospital, 21% measured
      outpatient referral from office/clinic, 71% measured program enrollment, and 74%
      measured program completion rates. Program-reported participation rates
      (interquartile range) were 68% (32-90) for hospital referral, 35% (15-60) for
      office/clinic referral, 70% (46-80) for enrollment, and 75% (62-82) for program
      completion. The majority of programs utilized a hospital-based systematic
      referral, liaison-facilitated referral, or inpatient CR program referral (64%,
      68%, and 60% of the time, respectively). Early appointments (<2 weeks) were
      utilized by 35%, and consistent phone call appointment reminders were utilized by
      50% of programs. Quality improvement (QI) projects were performed by about half
      of CR programs. Measurement of participation rates was highly correlated with
      performing QI projects (P < .0001.) CONCLUSIONS: : Although programs are aware of
      participation rate gaps, the monitoring of participation rates is suboptimal, QI
      initiatives are infrequent, and proven strategies for increasing patient
      participation are inconsistently utilized. These issues likely contribute to the
      national CR participation gap and may prove to be useful targets for national QI
      initiatives.

PMID- 25763924
TI  - The economic impact of implementing a multiple inflammatory biomarker-based
      approach to identify, treat, and reduce cardiovascular risk.
AB  - OBJECTIVES: To develop an economic model to estimate the change in the number of
      events and costs of non-fatal myocardial infarction (MI) and non-fatal ischemic
      stroke (IS) as a result of implementing routine risk-stratification with a
      multiple inflammatory biomarker approach. METHODS: Reductions in the numbers of
      non-fatal MI and non-fatal IS events and in related per-member-per-month (PMPM)
      and 5-year costs (excluding test costs) due to biomarker testing were modeled for
      a US health plan with one million beneficiaries. Inputs for the model included
      literature-based MI and IS incidence rates, healthcare costs associated with MI
      and IS, laboratory results of biomarker testing, MI and IS hazard ratios related
      to biomarker levels, patient monitoring and intervention costs and use/costs of
      preventative pharmacotherapy. Preventative pharmacotherapy inputs were based on
      an analysis of pharmacy claims data. Costs savings (2013 USD) were assessed for
      patients undergoing biomarker testing compared to the standard of care. Data from
      MDVIP and Cleveland Heart Lab supported two critical inputs: (1) treatment
      success rates and (2) the population distribution of biomarker testing. Incidence
      rates, hazard ratios, and other healthcare costs were obtained from the
      literature. RESULTS: For a health plan with one million members, an estimated
      21,104 MI and 22,589 IS events occurred in a 5-year period. Routine biomarker
      testing among a sub-group of beneficiaries >=35 years old reduced non-fatal MI
      and IS events by 2039 and 1869, respectively, yielding cost savings of over $187
      million over 5 years ($3.13 PMPM), excluding test costs. Results were sensitive
      to changes in treatment response rates. Nonetheless, cost savings were observed
      for all input values. CONCLUSIONS: This study suggests that health plans can
      realize substantial cost savings by preventing non-fatal MI and IS events after
      implementation of routine biomarker testing. Five-year cost savings before test
      costs could exceed $3.13 PMPM.

PMID- 25763923
TI  - Identification of differential microRNAs in cerebrospinal fluid and serum of
      patients with major depressive disorder.
AB  - Major depression is a debilitating disease. To date, the development of
      biomarkers of major depressive disorder (MDD) remains a challenge. Recently,
      alterations in the expression of microRNAs (miRNAs) from post-mortem brain tissue
      and peripheral blood have been linked to MDD. The goals of this study were to
      detect the differential miRNAs in cerebrospinal fluid (CSF) and serum of MDD
      patients. First, the relative expression levels of 179 miRNAs (relative high
      levels in serum) were analyzed by miRNA PCR Panel in the CSF of MDD patients.
      Then, the differentially altered miRNAs from CSF were further assessed by qRT-PCR
      in the serum of the same patients. Finally, the serum differentially altered
      miRNAs were further validated by qRT-PCR in the serum of another MDD patients.
      The CSF-results indicated that 11 miRNAs in MDD patients were significantly
      higher than these in control subjects, and 5 miRNAs were significantly lower than
      these in control subjects. The serum-results from the same patients showed that 3
      miRNAs (miR-221-3p, miR-34a-5p, and let-7d-3p) of the 11 miRNAs were
      significantly higher than these in control subjects, and 1 miRNA (miR-451a) of 5
      miRNAs was significantly lower than these in control subjects. The up-regulation
      of miR-221-3p, miR-34a-5p, let-7d-3p and down-regulation of miR-451a was further
      validated in another 32 MDD patients. ROC analysis showed that the area under
      curve of let-7d-3p, miR-34a-5p, miR-221-3p and miR-451a was 0.94, 0.98, 0.97 and
      0.94, with specificity of 90.48%, 95.24%, 90.48% and 90.48%, and sensitivity of
      93.75%, 96.88%, 90.63% and 84.85%, respectively. In addition, target gene
      prediction found that the altered miRNAs are involved in affecting some important
      genes and pathway related to MDD. Our results suggested that differentially
      altered miRNAs in CSF might be involved in MDD, and serum miR-221-3p, miR-34a-5p,
      let-7d-3p, and miR-451a might be able to serve as biomarkers for MDD. 

PMID- 25763925
TI  - Biodegradability of Poly-3-hydroxybutyrate/Bacterial Cellulose Composites under
      Aerobic Conditions, Measured via Evolution of Carbon Dioxide and Spectroscopic
      and Diffraction Methods.
AB  - Poly-3-hydroxybutyrate (PHB) and bacterial cellulose (BC) are both natural
      polymeric materials that have the potential to replace traditional, nonrenewable
      polymers. In particular, the nanofibrillar form of bacterial cellulose makes it
      an effective reinforcement for PHB. Neat PHB, bacterial cellulose, and a
      composite of PHB/BC produced with 10 wt % cellulose were composted under
      accelerated aerobic test conditions, with biodegradability measured by the carbon
      dioxide evolution method, in conjunction with spectroscopic and diffraction
      methods to assess crystallinity changes during the biodegradation process. The
      PHB/BC composite biodegraded at a greater rate and extent than that of PHB alone,
      reaching 80% degradation after 30 days, whereas PHB did not reach this level of
      degradation until close to 50 days of composting. The relative crystallinity of
      PHB and PHB in the PHB/BC composite was found to increase in the initial weeks of
      degradation, with degradation occurring primarily in the amorphous region of the
      material and some recrystallization of the amorphous PHB. Small angle X-ray
      scattering indicates that the change in PHB crystallinity is accompanied by a
      change in morphology of semicrystalline lamellae. The increased rate of
      biodegradability suggests that these materials could be applicable to single-use
      applications and could rapidly biodegrade in compost on disposal.

PMID- 25763926
TI  - Religious Conflict, Sexual Identity, and Suicidal Behaviors among LGBT Young
      Adults.
AB  - This is the first known study to explore how religious identity conflict impacts
      suicidal behaviors among lesbian, gay, bisexual, and transgender (LGBT) young
      adults and to test internalized homophobia as a mediator. A secondary analysis of
      2,949 youth was conducted using a national dataset collected by OutProud in 2000.
      Three indicators of identity conflict and an internalized-homophobia scale
      (mediator), were included in logistic regressions with three different suicide
      variable outcomes. Internalized homophobia fully mediates one conflict indicator
      and partially mediates the other two indicators' relationship with suicidal
      thoughts. Internalized homophobia also fully mediates the relationship between
      one conflict indicator and chronic suicidal thoughts. Two indicators were
      associated with twice the odds of a suicide attempt. LGBT young adults who mature
      in religious contexts have higher odds of suicidal thoughts, and more
      specifically chronic suicidal thoughts, as well as suicide attempt compared to
      other LGBT young adults. Internalized homophobia only accounts for portions of
      this conflict. 

PMID- 25763927
TI  - Women in print.

PMID- 25763928
TI  - Inter-Institutional Comparison of Personalized Risk Assessments for Second
      Malignant Neoplasms for a 13-Year-Old Girl Receiving Proton versus Photon
      Craniospinal Irradiation.
AB  - Children receiving radiotherapy face the probability of a subsequent malignant
      neoplasm (SMN). In some cases, the predicted SMN risk can be reduced by proton
      therapy. The purpose of this study was to apply the most comprehensive dose
      assessment methods to estimate the reduction in SMN risk after proton therapy vs.
      photon therapy for a 13-year-old girl requiring craniospinal irradiation (CSI).
      We reconstructed the equivalent dose throughout the patient's body from
      therapeutic and stray radiation and applied SMN incidence and mortality risk
      models for each modality. Excluding skin cancer, the risk of incidence after
      proton CSI was a third of that of photon CSI. The predicted absolute SMN risks
      were high. For photon CSI, the SMN incidence rates greater than 10% were for
      thyroid, non-melanoma skin, lung, colon, stomach, and other solid cancers, and
      for proton CSI they were non-melanoma skin, lung, and other solid cancers. In
      each setting, lung cancer accounted for half the risk of mortality. In
      conclusion, the predicted SMN risk for a 13-year-old girl undergoing proton CSI
      was reduced vs. photon CSI. This study demonstrates the feasibility of inter
      institutional whole-body dose and risk assessments and also serves as a model for
      including risk estimation in personalized cancer care. 

PMID- 25763930
TI  - Synthesis and characterization of bis-N-2-aryl triazole as a fluorophore.
AB  - Naphthalene-bridged bis-triazole (NBT) complexes were prepared and characterized
      for investigation of their photophysical properties. Unlike our previously
      reported N-2-aryl triazoles, which gave strong emissions through the planar
      intramolecular charge transfer mechanism (coplanar conformation), this newly
      developed NBT adopted a noncoplanar conformation between triazole and
      naphthalene, achieving fluorescence through twisted intramolecular charge
      transfer. 

PMID- 25763929
TI  - Research on single nucleotide polymorphisms interaction detection from network
      perspective.
AB  - Single Nucleotide Polymorphisms (SNPs) found in Genome-Wide Association Study
      (GWAS) mainly influence the susceptibility of complex diseases, but they still
      could not comprehensively explain the relationships between mutations and
      diseases. Interactions between SNPs are considered so important for deeply
      understanding of those relationships that several strategies have been proposed
      to explore such interactions. However, part of those methods perform poorly when
      marginal effects of disease loci are weak or absent, others may lack of
      considering high-order SNPs interactions, few methods have achieved the
      requirements in both performance and accuracy. Considering the above reasons, not
      only low-order, but also high-order SNP interactions as well as main-effect SNPs,
      should be taken into account in detection methods under an acceptable
      computational complexity. In this paper, a new pairwise (or low-order)
      interaction detection method IG (Interaction Gain) is introduced, in which
      disease models are not required and parallel computing is utilized. Furthermore,
      high-order SNP interactions were proposed to be detected by finding closely
      connected function modules of the network constructed from IG detection results.
      Tested by a wide range of simulated datasets and four WTCCC real datasets, the
      proposed methods accurately detected both low-order and high-order SNP
      interactions as well as disease-associated main-effect SNPS and it surpasses all
      competitors in performances. The research will advance complex diseases research
      by providing more reliable SNP interactions. 

PMID- 25763931
TI  - NFkappaB and Survivin-Mediated Radio-Adaptive Response.
AB  - A survivin-mediated radio-adaptive response was induced in SA-NH murine sarcoma
      cells following activation of nuclear transcription factor kappaB (NFkappaB) by
      very low doses of ionizing radiation of 5, 20 or 100 mGy. SA-NH cells and a clone
      stably transfected with a plasmid containing a mutated IkappaBalpha gene that
      prevents the activation of NFkappaB (SA-NH+mIkappaBalpha1) were used to
      investigate the role of NFkappaB activation in the development and expression of
      the survivin-mediated radio-adaptive response. Tumor cells were exposed to very
      low doses of radiation 30 min prior to or at times ranging from 30 min to 6 h
      after the first of two 2 Gy doses separated by 24 h under in vitro conditions.
      Evidence of very low dose radiation induced a radio-adaptive response only in SA
      NH but not SA-NH+mIkappaBalpha1 cells was shown by both an increase in SA-NH cell
      survival of 20-40% using a standard colony forming assay and reduced apoptosis
      frequencies of 20-40% as determined by the TUNEL assay. Changes in survivin
      protein levels as a function of irradiation conditions were monitored by Western
      blot. A 100 mGy exposure 30 min prior to a 2 Gy dose resulted in an elevation in
      total survivin protein 24 h later in SA-NH but not SA-NH+mIkappaBalpha1 cells.
      Transfection of cells with survivin siRNA inhibited elevation of survivin protein
      by very low dose radiation and the subsequent radio-adaptive response in SA-NH
      cells. These data suggest that the survivin-mediated radio-adaptive response is
      dependent upon the ability of cells to activate NFkappaB. 

PMID- 25763932
TI  - In memoriam: Robert Blair Painter.

PMID- 25763933
TI  - Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors from the
      natural origin: a recent perspective.
AB  - Overexpression of epidermal growth factor receptor (EGFR) is seen in a number of
      human tumors like prostate, colon, breast and ovarian. Their expression is
      correlated with vascularity and often difficult to diagnose. Though a number of
      active inhibitors and anticancer drugs against EGFR-tyrosine kinase are known,
      increase in resistance together with many side effects designate the need for new
      and improved treatments. Natural products and their analoges have significant
      contribution in the cancer drug discovery and development process. Therefore in
      the current review we mainly discuss design, synthesis and structural activity
      relationship of epidermal growth factor receptor (EGFR) tyrosine kinase
      inhibitors from the natural origin. 

PMID- 25763934
TI  - Targeting PI3Kdelta: emerging therapy for chronic lymphocytic leukemia and
      beyond.
AB  - Chronic lymphocytic leukemia (CLL) remains the most incurable leukemia. Early
      chemotherapeutic treatments, including alkylating agents, purine nucleoside
      derivatives, and immunotherapeutic antibodies, only show limited benefits for
      patients but severe off-target related side effects. Recent advances in
      understanding of the critical molecular pathways of regulating proliferation and
      survival of B-CLL cells have spurred a new therapeutical strategy by selectively
      targeting phosphoinositide 3-kinase delta (PI3Kdelta). Idelalisib, a first-in
      class PI3Kdelta-selective small molecule has received the FDA's fast-track
      approval in July of 2014 as a new treatment of CLL, indolent B-cell non-Hodgkin's
      lymphoma, and relapsed small lymphocytic lymphoma. Undoubtedly, the success of
      idelalisib has provided a solid support in the development of PI3Kdelta-specific
      inhibitors and reformed the concept of treating CLL. However, the number of
      reported selective inhibitors of PI3Kdelta is very limited and very few have
      advanced into clinical trials. The mechanism of their actions remains elusive.
      More profound understanding on the modes of action of new PI3Kdelta inhibitors
      will further validate the PI3Kdelta-targeting strategy, and help to identify
      biomarkers capable of stratifying patients who will most likely benefit from the
      therapy.

PMID- 25763935
TI  - A CH2Cl2 complex of a [Rh(pincer)](+) cation.
AB  - The CH2Cl2 complex [Rh((tBu)PONOP)(kappa(1)-ClCH2Cl)][BAr(F)4] is reported, that
      also acts as a useful synthon for other complexes such as N2, CO and H2 adducts;
      while the analogous PNP complex undergoes C-Cl activation. 

PMID- 25763936
TI  - Effects of weight loss on airway responsiveness in obese adults with asthma: does
      weight loss lead to reversibility of asthma?
AB  - BACKGROUND: The growing epidemics of obesity and asthma are major public health
      concerns. Although asthma-obesity links are widely studied, the effects of weight
      loss on asthma severity measured by airway hyperresponsiveness (AHR) have
      received limited attention. The main study objective was to examine whether
      weight reduction reduces asthma severity in obese adults with asthma. METHODS: In
      a prospective, controlled, parallel-group study, we followed 22 obese
      participants with asthma aged 18 to 75 years with a BMI >= 32.5 kg/m2 and AHR
      (provocative concentration of methacholine causing a 20% fall in FEV1 [PC20] < 16
      mg/mL). Sixteen participants followed a behavioral weight reduction program for 3
      months, and six served as control subjects. The primary outcome was change in AHR
      over 3 months. Changes in lung function, asthma control, and quality of life were
      secondary outcomes. RESULTS: At study entry, participant mean +/- SD age was 44
      +/- 9 years, 95% were women, and mean BMI was 45.7 +/- 9.2 kg/m2. After 3 months,
      mean weight loss was 16.5 +/- 9.9 kg in the intervention group, and the control
      group had a mean weight gain of 0.6 +/- 2.6 kg. There were significant
      improvements in PC20 (P = .009), FEV1 (P = .009), FVC (P = .010), asthma control
      (P < .001), and asthma quality of life (P = .003) in the intervention group, but
      these parameters remained unchanged in the control group. Physical activity
      levels also increased significantly in the intervention group but not in the
      control group. CONCLUSIONS: Weight loss in obese adults with asthma can improve
      asthma severity, AHR, asthma control, lung function, and quality of life. These
      findings support the need to actively pursue healthy weight-loss measures in this
      population.

PMID- 25763937
TI  - Bacteriological and virulence study of a Mycobacterium chimaera isolate from a
      patient in China.
AB  - A clinical isolate from a patient was identified as Mycobacterium chimaera, a
      recently identified species of nontuberculous Mycobacteria. The biochemical and
      molecular identity, drug sensitivity and virulence of this isolated strain were
      investigated. 16S rRNA, the 16S-23S ITS, hsp65 and rpoB were amplified, and their
      sequence similarities with other mycobacteria were analyzed. The minimum
      inhibitory concentrations of 22 anti-microbial agents against this isolate were
      established, and the virulence of the isolate was evaluated by intravenous
      injection into C57BL/6 mice using Mycobacterium tuberculosis H37Rv as a control
      strain. Growth and morphological characteristics and mycolic acid profile
      analysis revealed that this isolated strain was a member of the Mycobacterium
      avium complex. BLAST analysis of the amplified sequences showed that the isolated
      strain was closely related to M. chimaera. Susceptibility testing showed that the
      isolate was sensitive to rifabutin, rifapentine, clarithromycin, azithromycin,
      imipenem and cefoxitin. Bacterial load determination and tissue histopathology of
      the infected mice indicated that the isolate was highly virulent. The first case
      of M. chimaera infection in China was evaluated. The information derived from
      this case may offer valuable guidance for clinical diagnosis and treatment. 

PMID- 25763938
TI  - Production of centimeter-scale gradient patterns by graded elastomeric tip array.
AB  - Large-area patterned surfaces with chemical and/or morphological gradients have
      significant applications in biology, chemistry, and materials science. In this
      work, we developed a unique lithographic strategy to fabricate 2D and 3D gradient
      patterns with gradually varying feature size or height over centimeter-scale
      areas by utilizing a large-area polydimethylsiloxane (PDMS) tip array with
      programmable tip apex as a conformal photomask in near-field photolithography.
      Meanwhile, a new strategy was developed to create the PDMS tip array with graded
      apex size, which was employed to fabricate gradient patterns with the lateral
      feature sizes changing from sub-100 nm to several microns on one single substrate
      over macroscopic (square centimeter) areas. Furthermore, 3D gradient patterns
      with spatially varying feature height were enabled by employing gradient exposure
      dose. The formation of gradient feature size was ascribed either to gradient
      contact areas between tips and substrates or to exposure dose gradient. This
      lithography strategy combines the advantages of a wide range of feature sizes,
      simplicity, high-throughput, low-cost and diversified feature shapes, making it a
      facile and flexible approach to manufacture various functional gradient
      structures. 

PMID- 25763940
TI  - Spin-orbit-coupled Bose-Einstein condensates in a one-dimensional optical
      lattice.
AB  - We investigate a spin-orbit-coupled Bose-Einstein condensate loaded into a
      translating optical lattice. We experimentally demonstrate the lack of Galilean
      invariance in the spin-orbit-coupled system, which leads to anisotropic behavior
      of the condensate depending on the direction of translation of the lattice. The
      anisotropy is theoretically understood by an effective dispersion relation. We
      experimentally confirm this theoretical picture by probing the dynamical
      instability of the system. 

PMID- 25763941
TI  - Direct tests of measurement uncertainty relations: what it takes.
AB  - The uncertainty principle being a cornerstone of quantum mechanics, it is
      surprising that, in nearly 90 years, there have been no direct tests of
      measurement uncertainty relations. This lacuna was due to the absence of two
      essential ingredients: appropriate measures of measurement error (and
      disturbance) and precise formulations of such relations that are universally
      valid and directly testable. We formulate two distinct forms of direct tests,
      based on different measures of error. We present a prototype protocol for a
      direct test of measurement uncertainty relations in terms of value deviation
      errors (hitherto considered nonfeasible), highlighting the lack of universality
      of these relations. This shows that the formulation of universal, directly
      testable measurement uncertainty relations for state-dependent error measures
      remains an important open problem. Recent experiments that were claimed to
      constitute invalidations of Heisenberg's error-disturbance relation, are shown to
      conform with the spirit of Heisenberg's principle if interpreted as direct tests
      of measurement uncertainty relations for error measures that quantify distances
      between observables. 

PMID- 25763939
TI  - Smoking is associated with an increased risk of dementia: a meta-analysis of
      prospective cohort studies with investigation of potential effect modifiers.
AB  - BACKGROUND: Previous studies showed inconsistent results on the association of
      smoking with all-cause dementia and vascular dementia (VaD), and are limited by
      inclusion of a small number of studies and unexplained heterogeneity. Our review
      aimed to assess the risk of all-cause dementia, Alzheimer's disease (AD) and VaD
      associated with smoking, and to identify potential effect modifiers. METHODS AND
      FINDINGS: The PubMed, Embase, Cochrane Library and Psychinfo databases were
      searched to identify studies that provided risk estimates on smoking and
      incidence of dementia. A random-effects model was used to yield pooled results.
      Thirty-seven studies were included. Compared with never smokers, current smokers
      showed an increased risk of all-cause dementia (risk ratio (RR) 1.30, 95%
      confidence interval (CI) 1.18-1.45), AD (RR 1.40, 95% CI 1.13-1.73) and VaD (RR
      1.38, 95% CI 1.15-1.66). For all-cause dementia, the risk increased by 34% for
      every 20 cigarettes per day (RR 1.34, 95% CI 1.25-1.43). Former smokers did not
      show an increased risk of all-cause dementia (RR 1.01, 95% CI 0.96-1.06), AD (RR
      1.04, 95% CI 0.96-1.13) and VaD (RR 0.97, 95% CI 0.83-1.13). Subgroup analyses
      indicated that (1) the significantly increased risk of AD from current smoking
      was seen only in apolipoprotein E epsilon4 noncarriers; (2) current smokers aged
      65 to 75 years at baseline showed increased risk of all-cause dementia and AD
      compared to those aged over 75 or under 65 years; and (3) sex, race, study
      location and diagnostic criteria difference in risk of dementia was not found.
      CONCLUSIONS: Smokers show an increased risk of dementia, and smoking cessation
      decreases the risk to that of never smokers. The increased risk of AD from
      smoking is more pronounced in apolipoprotein E epsilon4 noncarriers. Survival
      bias and competing risk reduce the risk of dementia from smoking at extreme age.

PMID- 25763942
TI  - Compressibility of a fermionic mott insulator of ultracold atoms.
AB  - We characterize the Mott insulating regime of a repulsively interacting Fermi gas
      of ultracold atoms in a three-dimensional optical lattice. We use in situ imaging
      to extract the central density of the gas and to determine its local
      compressibility. For intermediate to strong interactions, we observe the
      emergence of a plateau in the density as a function of atom number, and a
      reduction of the compressibility at a density of one atom per site, indicating
      the formation of a Mott insulator. Comparisons to state-of-the-art numerical
      simulations of the Hubbard model over a wide range of interactions reveal that
      the temperature of the gas is of the order of, or below, the tunneling energy
      scale. Our results hold great promise for the exploration of many-body phenomena
      with ultracold atoms, where the local compressibility can be a useful tool to
      detect signatures of different phases or phase boundaries at specific values of
      the filling.

PMID- 25763943
TI  - Composable security proof for continuous-variable quantum key distribution with
      coherent States.
AB  - We give the first composable security proof for continuous-variable quantum key
      distribution with coherent states against collective attacks. Crucially, in the
      limit of large blocks the secret key rate converges to the usual value computed
      from the Holevo bound. Combining our proof with either the de Finetti theorem or
      the postselection technique then shows the security of the protocol against
      general attacks, thereby confirming the long-standing conjecture that Gaussian
      attacks are optimal asymptotically in the composable security framework. We
      expect that our parameter estimation procedure, which does not rely on any
      assumption about the quantum state being measured, will find applications
      elsewhere, for instance, for the reliable quantification of continuous-variable
      entanglement in finite-size settings. 

PMID- 25763944
TI  - Fermion-fermion scattering in quantum field theory with superconducting circuits.
AB  - We propose an analog-digital quantum simulation of fermion-fermion scattering
      mediated by a continuum of bosonic modes within a circuit quantum electrodynamics
      scenario. This quantum technology naturally provides strong coupling of
      superconducting qubits with a continuum of electromagnetic modes in an open
      transmission line. In this way, we propose qubits to efficiently simulate
      fermionic modes via digital techniques, while we consider the continuum
      complexity of an open transmission line to simulate the continuum complexity of
      bosonic modes in quantum field theories. Therefore, we believe that the
      complexity-simulating-complexity concept should become a leading paradigm in any
      effort towards scalable quantum simulations. 

PMID- 25763945
TI  - Constraining the 6.05 MeV 0+ and 6.13 MeV 3- cascade transitions in the
      12C(alpha,gamma)16O reaction using the asymptotic normalization coefficients.
AB  - The 12C(alpha,gamma)^16O reaction plays a fundamental role in astrophysics and
      needs to be known with accuracy better than 10%. Cascade gamma transitions
      through the excited states of 16 O are contributing to the uncertainty. We
      constrained the contribution of the 0+ (6.05 MeV) and 3- (6.13 MeV) cascade
      transitions by measuring the asymptotic normalization coefficients for these
      states using the alpha-transfer reaction 6 Li(12C,d)^16O at sub-Coulomb energy.
      The contribution of the 0+ and 3- cascade transitions at 300 keV is found to be
      1.96 +/- 0.3 and 0.12 +/- 0.04  keV b for destructive interference of the direct
      and resonance capture and 4.36 +/- 0.45 and 1.44 +/- 0.12  keV b for constructive
      interference, respectively. The combined contribution of the 0+ and 3- cascade
      transitions to the 12C(alpha,gamma)16O reaction cross section at 300 keV does not
      exceed 4%. Significant uncertainties have been dramatically reduced.

PMID- 25763946
TI  - Stability of anti-de sitter space in Einstein-Gauss-Bonnet gravity.
AB  - Recently it has been argued that in Einstein gravity anti-de Sitter spacetime is
      unstable against the formation of black holes for a large class of arbitrarily
      small perturbations. We examine the effects of including a Gauss-Bonnet term. In
      five dimensions, spherically symmetric Einstein-Gauss-Bonnet gravity has two key
      features: Choptuik scaling exhibits a radius gap, and the mass function goes to a
      finite value as the horizon radius vanishes. These suggest that black holes will
      not form dynamically if the total mass-energy content of the spacetime is too
      small, thereby restoring the stability of anti-de Sitter spacetime in this
      context. We support this claim with numerical simulations and uncover a rich
      structure in horizon radii and formation times as a function of perturbation
      amplitude. 

PMID- 25763947
TI  - Gravitational redshift of galaxies in clusters from the sloan digital sky survey
      and the Baryon Oscillation spectroscopic survey.
AB  - The gravitational redshift effect allows one to directly probe the gravitational
      potential in clusters of galaxies. Following up on Wojtak et al. [Nature (London)
      477, 567 (2011)], we present a new measurement. We take advantage of new data
      from the tenth data release of the Sloan Digital Sky Survey and the Baryon
      Oscillation Spectroscopic Survey. We compare the spectroscopic redshift of the
      brightest cluster galaxies (BCGs) with that of galaxies at the outskirts of
      clusters, using a sample with an average cluster mass of 1014M?. We find that
      these galaxies have an average relative redshift of -11  km/s compared with that
      of BCGs, with a standard deviation of +7 and -5  km/s. Our measurement is
      consistent with that of Wojtak et al. [Nature (London) 477, 567 (2011)]. However,
      our derived standard deviation is larger, as we take into account various
      systematic effects, beyond the size of the data set. The result is in good
      agreement with the predictions from general relativity.

PMID- 25763948
TI  - Accelerated gravitational wave parameter estimation with reduced order modeling.
AB  - Inferring the astrophysical parameters of coalescing compact binaries is a key
      science goal of the upcoming advanced LIGO-Virgo gravitational-wave detector
      network and, more generally, gravitational-wave astronomy. However, current
      approaches to parameter estimation for these detectors require computationally
      expensive algorithms. Therefore, there is a pressing need for new, fast, and
      accurate Bayesian inference techniques. In this Letter, we demonstrate that a
      reduced order modeling approach enables rapid parameter estimation to be
      performed. By implementing a reduced order quadrature scheme within the LIGO
      Algorithm Library, we show that Bayesian inference on the 9-dimensional parameter
      space of nonspinning binary neutron star inspirals can be sped up by a factor of
      ~30 for the early advanced detectors' configurations (with sensitivities down to
      around 40 Hz) and ~70 for sensitivities down to around 20 Hz. This speedup will
      increase to about 150 as the detectors improve their low-frequency limit to 10
      Hz, reducing to hours analyses which could otherwise take months to complete.
      Although these results focus on interferometric gravitational wave detectors, the
      techniques are broadly applicable to any experiment where fast Bayesian analysis
      is desirable. 

PMID- 25763949
TI  - Constraint on a varying proton-electron mass ratio 1.5 billion years after the
      big bang.
AB  - A molecular hydrogen absorber at a lookback time of 12.4 billion years,
      corresponding to 10% of the age of the Universe today, is analyzed to put a
      constraint on a varying proton-electron mass ratio, MU. A high resolution
      spectrum of the J1443+2724 quasar, which was observed with the Very Large
      Telescope, is used to create an accurate model of 89 Lyman and Werner band
      transitions whose relative frequencies are sensitive to MU, yielding a limit on
      the relative deviation from the current laboratory value of DeltaMU/MU=(-9.5 +/-
      5.4(stat)+/- 5.3(syst))*10(-6).

PMID- 25763950
TI  - Quantum field theory of fluids.
AB  - The quantum theory of fields is largely based on studying perturbations around
      noninteracting, or free, field theories, which correspond to a collection of
      quantum-mechanical harmonic oscillators. The quantum theory of an ordinary fluid
      is "freer", in the sense that the noninteracting theory also contains an infinite
      collection of quantum-mechanical free particles, corresponding to vortex modes.
      By computing a variety of correlation functions at tree and loop level, we give
      evidence that a quantum perfect fluid can be consistently formulated as a low
      energy, effective field theory. We speculate that the quantum behavior is
      radically different from both classical fluids and quantum fields. 

PMID- 25763951
TI  - Integrability and maximally helicity violating diagrams in n=4 supersymmetric
      yang-mills theory.
AB  - We apply maximally helicity violating (MHV) diagrams to the derivation of the one
      loop dilatation operator of N=4 supersymmetric Yang-Mills theory in the SO(6)
      sector. We find that in this approach the calculation reduces to the evaluation
      of a single MHV diagram in dimensional regularization. This provides the first
      application of MHV diagrams to an off-shell quantity. We also discuss other
      applications of the method and future directions. 

PMID- 25763952
TI  - Right-handed quark mixing in left-right symmetric theory.
AB  - We give exact formulas for the right-handed analog of the Cabibbo-Kobayashi
      Maskawa (CKM) matrix in the minimal left-right symmetric theory, for the case
      when the left-right symmetry is generalized parity as in the original version of
      the theory. We derive its explicit form and give a physical reason for the known
      and surprising fact that the right-handed mixing angles are close to the CKM
      ones, in spite of the left-right symmetry being badly broken in nature. We
      exemplify our results on the production of the right-handed charged gauge boson
      and the computation of K(L)-K(S) mass difference.

PMID- 25763953
TI  - Directional antineutrino detection.
AB  - We propose the first event-by-event directional antineutrino detector using
      inverse beta decay (IBD) interactions on hydrogen, with potential applications
      including monitoring for nuclear nonproliferation, spatially mapping
      geoneutrinos, characterizing the diffuse supernova neutrino background and
      searching for new physics in the neutrino sector. The detector consists of
      adjacent and separated target and capture scintillator planes. IBD events take
      place in the target layers, which are thin enough to allow the neutrons to escape
      without scattering elastically. The neutrons are detected in the thicker boron
      loaded capture layers. The location of the IBD event and the momentum of the
      positron are determined by tracking the positron's trajectory through the
      detector. Our design is a straightforward modification of existing antineutrino
      detectors; a prototype could be built with existing technology. 

PMID- 25763954
TI  - Production and elliptic flow of dileptons and photons in a matrix model of the
      quark-gluon plasma.
AB  - We consider a nonperturbative approach to the thermal production of dileptons and
      photons at temperatures near the critical temperature in QCD. The suppression of
      colored excitations at low temperature is modeled by including a small value of
      the Polyakov loop, in a "semi"-quark-gluon plasma (QGP). Comparing the semi-QGP
      to the perturbative QGP, we find a mild enhancement of thermal dileptons. In
      contrast, to leading logarithmic order in weak coupling there are far fewer hard
      photons from the semi-QGP than the usual QGP. To illustrate the possible effects
      on photon and dilepton production in heavy-ion collisions, we integrate the rate
      with a simulation using ideal hydrodynamics. Dileptons uniformly exhibit a small
      flow, but the strong suppression of photons in the semi-QGP tends to weight the
      elliptical flow of photons to that generated in the hadronic phase. 

PMID- 25763957
TI  - Dispersion engineering for vertical microcavities using subwavelength gratings.
AB  - We show that the energy-momentum dispersion of a vertical semiconductor
      microcavity can be modified by design using a high-index-contrast subwavelength
      grating (SWG) as a cavity mirror. We analyze the angular dependence of the
      reflection phase of the SWG to illustrate the principles of dispersion
      engineering. We show examples of engineered dispersions such as ones with much
      reduced or increased energy density of states and one with a double-well-shaped
      dispersion. This method of dispersion engineering is compatible with maintaining
      a high cavity quality factor and incorporating fully protected active media
      inside the cavity, thus enabling the creation of new types of cavity quantum
      electrodynamics systems. 

PMID- 25763958
TI  - Improved intrapulse raman scattering control via asymmetric airy pulses.
AB  - We experimentally demonstrate the possibility of tuning the frequency of a laser
      pulse via the use of an Airy pulse-seeded soliton self-frequency shift. The
      intrinsically asymmetric nature of Airy pulses, typically featured by either
      leading or trailing oscillatory tails (relatively to the main lobe), is revealed
      through the nonlinear generation of both a primary and a secondary Raman soliton
      self-frequency shift, a phenomenon which is driven by the soliton fission
      processes. The resulting frequency shift can be carefully controlled by using
      time-reversed Airy pulses or, alternatively, by applying an offset to the cubic
      phase modulation used to generate the pulses. When compared with the use of
      conventional chirped Gaussian pulses, our technique brings about unique
      advantages in terms of both efficient frequency tuning and feasibility, along
      with the generation and control of multicolor Raman solitons with enhanced
      tunability. Our theoretical analysis agrees well with our experimental
      observations. 

PMID- 25763960
TI  - Nonhelical inverse transfer of a decaying turbulent magnetic field.
AB  - In the presence of magnetic helicity, inverse transfer from small to large scales
      is well known in magnetohydrodynamic (MHD) turbulence and has applications in
      astrophysics, cosmology, and fusion plasmas. Using high resolution direct
      numerical simulations of magnetically dominated self-similarly decaying MHD
      turbulence, we report a similar inverse transfer even in the absence of magnetic
      helicity. We compute for the first time spectral energy transfer rates to show
      that this inverse transfer is about half as strong as with helicity, but in both
      cases the magnetic gain at large scales results from velocity at similar scales
      interacting with smaller-scale magnetic fields. This suggests that both inverse
      transfers are a consequence of universal mechanisms for magnetically dominated
      turbulence. Possible explanations include inverse cascading of the mean squared
      vector potential associated with local near two dimensionality and the shallower
      k^{2} subinertial range spectrum of kinetic energy forcing the magnetic field
      with a k^{4} subinertial range to attain larger-scale coherence. The inertial
      range shows a clear k^{-2} spectrum and is the first example of fully isotropic
      magnetically dominated MHD turbulence exhibiting weak turbulence scaling. 

PMID- 25763961
TI  - Breakdown of the fermi liquid description for strongly interacting fermions.
AB  - The nature of the normal state of an ultracold Fermi gas in the BCS-BEC crossover
      regime is an intriguing and controversial topic. While the many-body ground state
      remains a condensate of paired fermions, the normal state must evolve from a
      Fermi liquid to a Bose gas of molecules as a function of the interaction
      strength. How this occurs is still largely unknown. We explore this question with
      measurements of the distribution of single-particle energies and momenta in a
      nearly homogeneous gas above T(c). The data fit well to a function that includes
      a narrow, positively dispersing peak that corresponds to quasiparticles and an
      "incoherent background" that can accommodate broad, asymmetric line shapes. We
      find that the quasiparticle's spectral weight vanishes abruptly as the strength
      of interactions is modified, which signals the breakdown of a Fermi liquid
      description. Such a sharp feature is surprising in a crossover.

PMID- 25763956
TI  - Two-dimensional spectroscopy for the study of ion coulomb crystals.
AB  - Ion Coulomb crystals are currently establishing themselves as a highly
      controllable test bed for mesoscopic systems of statistical mechanics. The
      detailed experimental interrogation of the dynamics of these crystals, however,
      remains an experimental challenge. In this work, we show how to extend the
      concepts of multidimensional nonlinear spectroscopy to the study of the dynamics
      of ion Coulomb crystals. The scheme we present can be realized with state-of-the
      art technology and gives direct access to the dynamics, revealing nonlinear
      couplings even in the presence of thermal excitations. We illustrate the
      advantages of our proposal showing how two-dimensional spectroscopy can be used
      to detect signatures of a structural phase transition of the ion crystal, as well
      as resonant energy exchange between modes. Furthermore, we demonstrate in these
      examples how different decoherence mechanisms can be identified. 

PMID- 25763959
TI  - Observation of deflection of a beam of multi-GeV electrons by a thin crystal.
AB  - We report on an experiment performing channeling and volume reflection of a high
      energy electron beam using a quasimosaic, bent silicon (111) crystal at the End
      Station A Test Beam at SLAC. The experiment uses beams of 3.35 and 6.3 GeV. In
      the channeling orientation, deflections of the beam of 400 MUrad for both
      energies with about 22% efficiency are observed, while in the volume-reflection
      orientation, deflection of the beam by 120 MUrad at 3.35 GeV and by 80 MUrad at
      6.3 GeV is observed with 86%-95% efficiency. Quantitative measurements of the
      channeling efficiency, surface transmission, and dechanneling length are taken.
      These are the first quantitative measurements of channeling and volume reflection
      using a primary beam of multi-GeV electrons.

PMID- 25763962
TI  - Nanomechanics of bidentate thiolate ligands on gold surfaces.
AB  - The effect of the chain length separating sulfur atoms in bidentate thiols
      attached to defective gold surfaces on the rupture of the respective molecule
      gold junctions has been studied computationally. Thermal desorption always yields
      cyclic disulfides. In contrast, mechanochemical desorption leads to cyclic gold
      complexes, where metal atoms are extracted from the surface and kept in tweezer
      like arrangements by the sulfur atoms. This phenomenon is rationalized in terms
      of directional mechanical manipulation of Au-Au bonds and Au-S coordination
      numbers. Moreover, the flexibility of the chain is shown to crucially impact on
      the mechanical strength of the junction. 

PMID- 25763963
TI  - Structure and local chemical properties of boron-terminated tetravacancies in
      hexagonal boron nitride.
AB  - Imaging and spectroscopy performed in a low-voltage scanning transmission
      electron microscope are used to characterize the structure and chemical
      properties of boron-terminated tetravacancies in hexagonal boron nitride. We
      confirm earlier theoretical predictions about the structure of these defects and
      identify new features in the electron energy-loss spectra of B atoms using high
      resolution chemical maps, highlighting differences between these areas and
      pristine sample regions. We correlate our experimental data with calculations
      which help explain our observations. 

PMID- 25763964
TI  - Ground-state degeneracy of topological phases on open surfaces.
AB  - We relate the ground state degeneracy of a non-Abelian topological phase on a
      surface with boundaries to the anyon condensates that break the topological phase
      into a trivial phase. Specifically, we propose that gapped boundary conditions of
      the surface are in one-to-one correspondence with the sets of condensates, each
      being able to completely break the phase, and we substantiate this by examples.
      The ground state degeneracy resulting from a particular boundary condition
      coincides with the number of confined topological sectors due to the
      corresponding condensation. These lead to a generalization of the Laughlin-Tao-Wu
      charge-pumping argument for Abelian fractional quantum Hall states to encompass
      non-Abelian topological phases, in the sense that an anyon loop of a confined
      anyon winding a nontrivial cycle can pump a condensed anyon from one boundary to
      another. Such generalized pumping may find applications in quantum control of
      anyons, eventually realizing topological quantum computation. 

PMID- 25763965
TI  - Gapped domain walls, gapped boundaries, and topological degeneracy.
AB  - Gapped domain walls, as topological line defects between (2+1)D topologically
      ordered states, are examined. We provide simple criteria to determine the
      existence of gapped domain walls, which apply to both Abelian and non-Abelian
      topological orders. Our criteria also determine which (2+1)D topological orders
      must have gapless edge modes, namely, which (1+1)D global gravitational anomalies
      ensure gaplessness. Furthermore, we introduce a new mathematical object, the
      tunneling matrix W, whose entries are the fusion-space dimensions W(ia), to label
      different types of gapped domain walls. By studying many examples, we find
      evidence that the tunneling matrices are powerful quantities to classify
      different types of gapped domain walls. Since a gapped boundary is a gapped
      domain wall between a bulk topological order and the vacuum, regarded as the
      trivial topological order, our theory of gapped domain walls inclusively contains
      the theory of gapped boundaries. In addition, we derive a topological ground
      state degeneracy formula, applied to arbitrary orientable spatial 2-manifolds
      with gapped domain walls, including closed 2-manifolds and open 2-manifolds with
      gapped boundaries.

PMID- 25763966
TI  - Spin polarization of the split Kondo state.
AB  - Spin-resolved scanning tunneling microscopy is employed to quantitatively
      determine the spin polarization of the magnetic field-split Kondo state.
      Tunneling conductance spectra of a Kondo-screened magnetic atom are evaluated
      within a simple model taking into account inelastic tunneling due to spin
      excitations and two Kondo peaks positioned symmetrically around the Fermi energy.
      We fit the spin state of the Kondo-screened atom with a spin Hamiltonian
      independent of the Kondo effect and account for Zeeman splitting of the Kondo
      peak in the magnetic field. We find that the width and the height of the Kondo
      peaks scales with the Zeeman energy. Our observations are consistent with full
      spin polarization of the Kondo peaks, i.e., a majority spin peak below the Fermi
      energy and a minority spin peak above. 

PMID- 25763967
TI  - Gap reversal at filling factors 3+1/3 and 3+1/5: towards novel topological order
      in the fractional quantum Hall regime.
AB  - In the region of the second Landau level several theories predict fractional
      quantum Hall states with novel topological order. We report the opening of an
      energy gap at the filling factor nu=3+1/3, firmly establishing the ground state
      as a fractional quantum Hall state. This and other odd-denominator states
      unexpectedly break particle-hole symmetry. Specifically, we find that the
      relative magnitudes of the energy gaps of the nu=3+1/3 and 3+1/5 states from the
      upper spin branch are reversed when compared to the nu=2+1/3 and 2+1/5
      counterpart states in the lower spin branch. Our findings raise the possibility
      that at least one of the former states is of an unusual topological order. 

PMID- 25763968
TI  - Aharonov-Bohm oscillations in singly connected disordered conductors.
AB  - We show that the transport and thermodynamic properties of a singly connected
      disordered conductor exhibit quantum Aharonov-Bohm oscillations as a function of
      the total magnetic flux through the sample. The oscillations are associated with
      the interference contribution from a special class of electron trajectories
      confined to the surface of the sample. 

PMID- 25763969
TI  - Universal increase in the superconducting critical temperature of two-dimensional
      semiconductors at low doping by the electron-electron interaction.
AB  - In two-dimensional multivalley semiconductors, at low doping, even a moderate
      electron-electron interaction enhances the response to any perturbation inducing
      a valley polarization. If the valley polarization is due to the electron-phonon
      coupling, the electron-electron interaction results in an enhancement of the
      superconducting critical temperature. By performing first-principles calculations
      beyond density functional theory, we prove that this effect accounts for the
      unconventional doping dependence of the superconducting transition temperature
      (T(c)) and of the magnetic susceptibility measured in Li(x)ZrNCI. Finally, we
      discuss what are the conditions for a maximal T(c) enhancement in weakly doped
      two-dimensional semiconductors.

PMID- 25763970
TI  - Measurement of critical currents of superconducting aluminum nanowires in
      external magnetic fields: evidence for a Weber blockade.
AB  - We have studied the critical current as a function of magnetic field in short and
      narrow superconducting aluminum nanowires. In the range of magnetic fields in
      which vortices can enter a nanowire in a single row, we find regular oscillations
      of the critical current as a function of magnetic field, with each oscillation
      corresponding to adding a single vortex to the nanowire. In this regime, the
      nanowires behave as quantum dots for vortices. As a function of current and
      magnetic field, we find diamond-shaped regions in which the resistance is zero
      and the number of vortices is fixed. 

PMID- 25763971
TI  - Constraints on topological order in mott insulators.
AB  - We point out certain symmetry induced constraints on topological order in Mott
      insulators (quantum magnets with an odd number of spin 1/2 moments per unit
      cell). We show, for example, that the double-semion topological order is
      incompatible with time reversal and translation symmetry in Mott insulators. This
      sharpens the Hastings-Oshikawa-Lieb-Schultz-Mattis theorem for 2D quantum
      magnets, which guarantees that a fully symmetric gapped Mott insulator must be
      topologically ordered, but is silent about which topological order is permitted.
      Our result applies to the kagome lattice quantum antiferromagnet, where recent
      numerical calculations of the entanglement entropy indicate a ground state
      compatible with either toric code or double-semion topological order. Our result
      rules out the latter possibility. 

PMID- 25763972
TI  - Hyperhoneycomb Iridate beta-Li2IrO3 as a platform for Kitaev magnetism.
AB  - A complex iridium oxide beta-Li(2)IrO(3) crystallizes in a hyperhoneycomb
      structure, a three-dimensional analogue of honeycomb lattice, and is found to be
      a spin-orbital Mott insulator with J(eff)=1/2 moment. Ir ions are connected to
      the three neighboring Ir ions via Ir-O(2)-Ir bonding planes, which very likely
      gives rise to bond-dependent ferromagnetic interactions between the J(eff)=1/2
      moments, an essential ingredient of Kitaev model with a spin liquid ground state.
      Dominant ferromagnetic interaction between J(eff)=1/2 moments is indeed confirmed
      by the temperature dependence of magnetic susceptibility chi(T) which shows a
      positive Curie-Weiss temperature theta(CW)~+40  K. A magnetic ordering with a
      very small entropy change, likely associated with a noncollinear arrangement of
      J(eff)=1/2 moments, is observed at T(c)=38  K. With the application of magnetic
      field to the ordered state, a large moment of more than 0.35  MU(B)/Ir is induced
      above 3 T, a substantially polarized J(eff)=1/2 state. We argue that the close
      proximity to ferromagnetism and the presence of large fluctuations evidence that
      the ground state of hyperhoneycomb beta-Li(2)IrO(3) is located in close proximity
      of a Kitaev spin liquid.

PMID- 25763973
TI  - Stochastic phenotype transition of a single cell in an intermediate region of
      gene state switching.
AB  - Multiple phenotypic states often arise in a single cell with different gene
      expression states that undergo transcription regulation with positive feedback.
      Recent experiments show that, at least in E.coli, the gene state switching can be
      neither extremely slow nor exceedingly rapid as many previous theoretical
      treatments assumed. Rather, it is in the intermediate region which is difficult
      to handle mathematically. Under this condition, from a full chemical-master
      equation description we derive a model in which the protein copy number, for a
      given gene state, follows a deterministic mean-field description while the
      protein-synthesis rates fluctuate due to stochastic gene state switching. The
      simplified kinetics yields a nonequilibrium landscape function, which, similar to
      the energy function for equilibrium fluctuation, provides the leading orders of
      fluctuations around each phenotypic state, as well as the transition rates
      between the two phenotypic states. This rate formula is analogous to Kramers'
      theory for chemical reactions. The resulting behaviors are significantly
      different from the two limiting cases studied previously.

PMID- 25763974
TI  - Universality in the morphology and mechanics of coarsening amyloid fibril
      networks.
AB  - Peptide hydrogels have important applications as biomaterials and in
      nanotechnology, but utilization often depends on their mechanical properties for
      which we currently have no predictive capability. Here we use a peptide model to
      simulate the formation of percolating amyloid fibril networks and couple these to
      the elastic network theory to determine their mechanical properties. We find that
      the time variation of network length scales can be collapsed onto master curves
      by using a time scaling function that depends on the peptide interaction
      anisotropy. The same scaling applies to network mechanics, revealing a
      nonmonotonic dependence of the shear modulus with time. Our structure-function
      relationship between the peptide building blocks, network morphology, and network
      mechanical properties can aid in the design of amyloid fibril networks with
      tailored mechanical properties. 

PMID- 25763975
TI  - Kinesin-8 motors improve nuclear centering by promoting microtubule catastrophe.
AB  - In fission yeast, microtubules push against the cell edge, thereby positioning
      the nucleus in the cell center. Kinesin-8 motors regulate microtubule
      catastrophe; however, their role in nuclear positioning is not known. Here we
      develop a physical model that describes how kinesin-8 motors affect nuclear
      centering by promoting a microtubule catastrophe. Our model predicts the improved
      centering of the nucleus in the presence of motors, which we confirmed
      experimentally in living cells. The model also predicts a characteristic time for
      the recentering of a displaced nucleus, which is supported by our experiments
      where we displaced the nucleus using optical tweezers. 

PMID- 25763976
TI  - Switching bonds in a DNA gel: an all-DNA vitrimer.
AB  - We design an all-DNA system that behaves like vitrimers, innovative plastics with
      self-healing and stress-releasing properties. The DNA sequences are engineered to
      self-assemble first into tetra- and bifunctional units which, upon further
      cooling, bind to each other forming a fully bonded network gel. An innovative
      design of the binding regions of the DNA sequences, exploiting a double toehold
      mediated strand displacement, generates a network gel which is able to reshuffle
      its bonds, retaining at all times full bonding. As in vitrimers, the rate of bond
      switching can be controlled via a thermally activated catalyst, which in the
      present design is very short DNA strands. 

PMID- 25763977
TI  - Dynamical criticality in the collective activity of a population of retinal
      neurons.
AB  - Recent experimental results based on multielectrode and imaging techniques have
      reinvigorated the idea that large neural networks operate near a critical point,
      between order and disorder. However, evidence for criticality has relied on the
      definition of arbitrary order parameters, or on models that do not address the
      dynamical nature of network activity. Here we introduce a novel approach to
      assess criticality that overcomes these limitations, while encompassing and
      generalizing previous criteria. We find a simple model to describe the global
      activity of large populations of ganglion cells in the rat retina, and show that
      their statistics are poised near a critical point. Taking into account the
      temporal dynamics of the activity greatly enhances the evidence for criticality,
      revealing it where previous methods would not. The approach is general and could
      be used in other biological networks. 

PMID- 25763978
TI  - Correction to High purcell factor due to coupling of a single emitter to a
      dielectric slot waveguide.

PMID- 25763979
TI  - Surgery for nonarteritic anterior ischemic optic neuropathy.
AB  - BACKGROUND: Nonarteritic anterior ischemic optic neuropathy (NAION) is
      characterized by sudden and painless loss of vision in the eye, accompanied by
      pallid swelling of the optic disc. Its etiology is unknown and no medical therapy
      has been proven effective in treating this condition. Optic nerve decompression
      surgery, a proposed treatment for NAION, involves making two or more slits or a
      window in the tissue surrounding the optic nerve, thereby allowing cerebrospinal
      fluid to escape, and theoretically reducing the pressure surrounding the optic
      nerve. OBJECTIVES: The objective of this review was to assess the safety and
      efficacy of surgery compared with other treatment or no treatment in people with
      NAION. SEARCH METHODS: We searched CENTRAL (which contains the Cochrane Eyes and
      Vision Group Trials Register) (2014, Issue 10), Ovid MEDLINE, Ovid MEDLINE In
      Process and Other Non-Indexed Citations, Ovid MEDLINE Daily, Ovid OLDMEDLINE
      (January 1946 to October 2014), EMBASE (January 1980 to October 2014), PubMed
      (1948 to October 2014), the metaRegister of Controlled Trials (mRCT)
      (www.controlled-trials.com), ClinicalTrials.gov (www.clinicaltrials.gov) and the
      World Health Organization (WHO) International Clinical Trials Registry Platform
      (ICTRP) (www.who.int/ictrp/search/en). There were no date or language
      restrictions in the electronic searches for trials. We last searched the
      electronic databases on 23 October 2014. SELECTION CRITERIA: All randomized
      trials of surgical treatment of NAION were eligible for inclusion in this review.
      DATA COLLECTION AND ANALYSIS: From full-text copies of all reports from relevant
      trials, one author extracted data which were verified by another author. No data
      synthesis was required. MAIN RESULTS: The one included trial, in which 258
      participants were randomized, was stopped early for futility. At the time of the
      24-month report the follow-up rate was 95.3% for six months and 67.4% for 24
      months (174 participants; 89 careful follow-up and 85 surgery). There was no
      evidence of a benefit of surgery on visual acuity. Measurements of visual acuity
      and visual fields were performed by a technician masked to the treatment
      received. At six months 32.0% of the surgery group had improved visual acuity by
      3 or more lines compared with 42.6% of the careful follow-up group (unadjusted
      risk ratio (RR) 0.75, 95% confidence interval (CI) 0.54 to 1.04). At 24 months
      29.4% of the surgery group had improved compared with 31.0% of the careful follow
      up group (unadjusted RR 0.95, 95% CI 0.60 to 1.49). Participants who underwent
      surgery more often lost 3 or more lines of visual acuity in the study eye,
      although the increased risk was not statistically significant. At six months
      18.9% in the surgery group had worsened visual acuity in the study eye compared
      with 14.8% in the careful follow-up group (RR 1.28; 95% CI 0.73 to 2.24). At 24
      months 20.0% in the surgery group had worsened visual acuity in the study eye
      compared with 21.8% in the careful follow-up group (RR 0.92; 95% CI 0.51 to
      1.64). Participants who received surgery experienced both intraoperative and
      postoperative adverse events, including central retinal artery occlusion during
      surgery and light perception vision at six months (one participant); and
      immediate loss of light perception following surgery and loss of vision that
      persisted to the 12-month visit (two participants). In the careful follow-up
      group, two participants had no light perception at the six-month follow-up visit;
      one of these had improved to light perception at 12 months. Pain was the most
      common adverse event in the surgery group (17% in surgery group versus 3% in the
      careful follow-up group at one week). Diplopia (double vision) was the next most
      common complication (8% in the surgery group versus 1% in the careful follow-up
      group at one week); at three months there was no statistically significant
      difference in proportion of participants with diplopia between the two groups.
      AUTHORS' CONCLUSIONS: The only eligible trial provided no evidence of a
      beneficial effect of optic nerve decompression surgery for NAION. Future research
      should focus on increasing our understanding of the etiology and prognosis of
      NAION. New treatment options should be examined in the context of randomized
      clinical trials.

PMID- 25763981
TI  - Correctional mental health in the USA.
AB  - PURPOSE: The purpose of this paper is to discuss five domains impacted by the
      transformation of correctional mental health care in the USA: public health,
      public safety, legal obligations, fiscal responsibility and ethical standards, as
      well as critical issues such as administrative segregation, suicide prevention
      and reentry planning. DESIGN/METHODOLOGY/APPROACH: In the last four decades, the
      USA has seen a sizable growth in its criminal justice system and corrections
      population. It has also seen reductions in civil and community-based mental
      health care. Persons with mental disabilities have come to represent a highly
      disproportional segment of the corrections population. The paper discusses the
      implications and underlying causes of these developments as well as recent
      responses to them. FINDINGS: This set of circumstances is starting to change the
      mission of correctional health services from crisis intervention and suicide
      prevention to include preparation for the inmate's almost inevitable return to
      the community. ORIGINALITY/VALUE: Such changes have led to further developments
      in correctional mental health care, in particular, policy designed to treat
      mental illness, reduce its destructive outcomes such as suicide, and facilitate
      successful reentry into the community in attempts to reduce recidivism and
      improve clinical outcomes. Mental health care professionals working within
      corrections have likewise faced ethical challenges in effectuating treatment.

PMID- 25763980
TI  - Fibrinogen-like protein 2/fibroleukin induces long-term allograft survival in a
      rat model through regulatory B cells.
AB  - We previously described that in a rat model of heart transplantation tolerance
      was dependent on CD8+CD45RClow Tregs that over-expressed fibrinogen-like protein
      2 (FGL2)/fibroleukin. Little is known on the immunoregulatory properties of FGL2.
      Here we analyzed the transplantation tolerance mechanisms that are present in
      Lewis 1A rats treated with FGL2. Over-expression of FGL2 in vivo through
      adenovirus associated virus -mediated gene transfer without any further treatment
      resulted in inhibition of cardiac allograft rejection. Adoptive cell transfer of
      splenocytes from FGL2-treated rats with long-term graft survival (> 80 days) in
      animals that were transplanted with cardiac allografts inhibited acute and
      chronic organ rejection in a donor-specific and transferable tolerance manner,
      since iterative adoptive transfer up to a sixth consecutive recipient resulted in
      transplantation tolerance. Adoptive cell transfer also efficiently inhibited anti
      donor antibody production. Analysis of all possible cell populations among
      splenocytes revealed that B lymphocytes were sufficient for this adoptive cell
      tolerance. These B cells were also capable of inhibiting the proliferation of
      CD4+ T cells in response to allogeneic stimuli. Moreover, gene transfer of FGL2
      in B cell deficient rats did not prolong graft survival. Thus, this is the first
      description of FGL2 resulting in long-term allograft survival. Furthermore,
      allograft tolerance was transferable and B cells were the main cells responsible
      for this effect. 

PMID- 25763982
TI  - Health promotion and prison settings.
AB  - PURPOSE: The purpose of this paper is to examine the contribution of modern
      correctional service in health promotion exemplified by the case study of
      Norwegian health promotion policies in prison settings.
      DESIGN/METHODOLOGY/APPROACH: This paper applies a two-fold methodology. First a
      narrative systematic literature review based on the Norwegian policy documents
      relevant for correctional settings is conducted. This is followed by a general
      review of the literature on the principles of humane service delivery in offender
      rehabilitation. FINDINGS: Alongside the contribution of the Risk-Need
      Responsivity Model in corrections and prevention of reoffending, the findings
      demonstrate an evident involvement of Norway in health promotion through
      authentic health promoting actions applied in prison settings. The actions are
      anchored in health policy's overarching goals of equity and "health in all public
      policy" aiming to reduce social inequalities in population health.
      ORIGINALITY/VALUE: In order to achieve a potential success of promoting health in
      correctional settings, policy makers have much to gain from endorsing a dialogue
      that respects the unique contributions of correctional research and health
      promotion. Focussing on inter-agency partnership and interdisciplinary
      collaboration between humane services may result in promising outcomes for
      individual, community and public health gain. The organizational factors and
      community involvement may be a significant aspect in prisoner rehabilitation,
      reentry and reintegration.

PMID- 25763983
TI  - When prison is "easier": probationers' perceptions of health and wellbeing.
AB  - PURPOSE: There are currently over 300,000 offenders in England and Wales and the
      majority, around 240,000, are in the community on probation. However, there is a
      paucity of research on their health and healthcare needs. The purpose of this
      paper is to explore issues around health and access to health services for those
      on probation. In particular the paper explores what people on probation consider
      to be the key health issues currently affecting them, and to identify barriers to
      accessing healthcare in the community. DESIGN/METHODOLOGY/APPROACH: The authors
      ran six focus groups with a total of 41 participants; two were with staff and the
      others with men and women on probation. In each focus group, the researchers used
      semi-structured guide and the discussions were recorded electronically and then
      transcribed. The paper adopted a thematic analytical framework and used NVivo 7
      to facilitate analysis. FINDINGS: Both probationers and professionals largely
      agreed about the key issues which included substance use and mental health
      problems. However, the most important issue for probationers was dealing with the
      stress of being on probation which was not generally recognised by professionals.
      All participants recognised the impact of issues such as housing, finances and
      employment on the wellbeing of probationers and were concerned about the lack of
      access to health services, in particular mental health and alcohol services.
      RESEARCH LIMITATIONS/IMPLICATIONS: This was a small study conducted in one part
      of England and therefore it is not clear that the findings are generalisable.
      However, it raises important issues about the mental health needs of probationers
      and the lack of appropriate services for them. Effective services may have
      positive impact on re-offending and further research is needed to evaluate models
      of care. PRACTICAL IMPLICATIONS: The challenge remains for local health service
      commissioners and providers and the probation service to work together to provide
      appropriate and accessible services for all those on probation.
      ORIGINALITY/VALUE: Nearly one-quarter of a million people are on probation at any
      one time in the UK but the existing evidence on their health is patchy and dated.
      Little is known about effective health interventions or the extent to which their
      health needs are met. This study shows that probationers see the stress of being
      on probation as their most important health concern. Both probationers and staff
      recognise that mental health and substance use are persistent problems and that
      these important health needs in these areas are not being met by existing
      services.

PMID- 25763984
TI  - Evaluation of an e-learning package to improve understanding of blood-borne
      viruses amongst prison staff in Wales, UK.
AB  - PURPOSE: The purpose of this paper is to provide education on blood-borne viruses
      (BBVs) to prison staff to help reduce stigma within the prisons, improve the care
      prisoners receive and reduce the risk of occupational transmission.
      DESIGN/METHODOLOGY/APPROACH: An e-module was used to improve staff understanding
      of hepatitis B (HBV), hepatitis C (HCV) and HIV at a prison in Wales, UK. An
      assessment was used to gather data on prison staff understanding of BBVs prior to
      undertaking the e-module. FINDINGS: In total, 530/697 (76 per cent) prison staff
      completed the BBV e-module. Average pre- and post-course assessment scores were
      8.6/11 and 10.85/11, respectively. Most staff understood the modes of hepatitis
      transmission, however, gaps in understanding were highlighted. In total, 22 per
      cent of staff believed HBV and HCV were airborne, 9 per cent believed
      transmission occurred through sharing cutlery. In total, 31 per cent of staff
      believed prisoners with hepatitis should declare their status to the prison.
      Practical implications: The e-module significantly improved staff understanding
      of BBVs and should be incorporated into future prison training packages. Future
      education should include how BBVs are not transmitted with an emphasis on casual
      contact. Medical confidentiality in prisons should also be addressed. Improving
      understanding will help reduce the stigma of BBVs within prison and improve the
      multidisciplinary care the prisoner receives. ORIGINALITY/VALUE: To the authors
      knowledge this is the first published evaluation of a BBV learning package for
      custodial staff. Evaluation of this educational package demonstrates a unique and
      valuable insight into the general understanding of BBVs by prison staff in Wales,
      UK.

PMID- 25763985
TI  - Bridging community and prison for older adults: invoking human rights and elder
      and intergenerational family justice.
AB  - PURPOSE: Older adults in prison present a significant health and human rights
      challenge for the criminal justice system. To date, there is no known study that
      provides a comprehensive examination or portrait of older persons in prison. The
      purpose of this paper is to understand individual, family, system, and community
      vulnerabilities that can complicate successful community reintegration for these
      individuals. DESIGN/METHODOLOGY/APPROACH: This study provides a cross-sectional,
      descriptive analysis of biopsychosocial, spiritual, and prison use
      characteristics associated with a sample of 677 older prisoners, aged 50+, in a
      state-wide prison system. FINDINGS: Results indicate the extent of diversity
      within this population based on demographic, clinical, social, legal profiles,
      prison service use patterns, and professional and personal contacts. RESEARCH
      LIMITATIONS/IMPLICATIONS: Due to the diversity within this population, an
      interdisciplinary approach is needed to address the complex social and health
      care needs of an aging prison population and to plan for their reentry. Practical
      implications - These findings suggest the need for holistic prevention,
      assessment, and interventions to interrupt the social-structural disparities that
      foster and support pathways to incarceration and recidivism. ORIGINALITY/VALUE:
      The human rights implications for the current treatment of older adults in prison
      include providing in-prison treatment that promotes safety, well-being,
      reconciliation, and seamless bridges between prison and community for older
      adults and their families. The True Grit Program is presented as an example of a
      humanistic and holistic approach of such an approach.

PMID- 25763986
TI  - Associations Among Symptoms of Autism, Symptoms of Depression and Executive
      Functions in Children with High-Functioning Autism: A 2 Year Follow-Up Study.
AB  - This study investigated the course of and association among changes in autism
      symptoms, depression symptoms and executive functions (EF) in children with high
      functioning autism (HFA). Thirty-four children with HFA and 45 typically
      developing children (age 9-16) were assessed at baseline and after 2 years.
      Children with HFA had impaired scores on all measures at both time points.
      According to parent reports, depressive symptoms decreased over time, while EF
      improved and autism symptoms were stable. Children's reports did not reveal less
      depressive symptoms over time. A positive association was found only between
      changes in autism symptoms and changes in symptoms of depression. A possible
      implication is that interventions aimed at either autism symptoms or symptoms of
      depression may improve the other.

PMID- 25763987
TI  - Variation of milk intake over time: clinical and pharmacokinetic implications.

PMID- 25763988
TI  - Reduction of hypoglycaemic events with a behavioural intervention: a randomized
      clinical trial for paediatric patients with Type 1 diabetes mellitus.
AB  - AIMS: To determine if a low-intensity, clinic-integrated behavioural intervention
      reduced the incidence of hypoglycaemic events in children with Type 1 diabetes.
      METHODS: A total of 390 families with children with Type 1 diabetes were enrolled
      in a 2-year, randomized clinical trial of a behavioural intervention. The
      intervention was designed to improve diabetes management practices by targeting
      the family's diabetes problem-solving skills. Hypoglycaemic events were
      categorized in two groups: those treated by oral ingestion and those treated by
      parenteral therapy. Events were self-reported by participants at each clinic
      visit, which occurred approximately every 3-4 months. Analyses included two
      sample t-tests, the mean cumulative function test, and the Cox proportional
      hazards model for recurrent events to compare the incidence between groups.
      RESULTS: Across the entire 2-year study period, the incidence of hypoglycaemic
      events treated by oral ingestion of glucose-rich foods and events requiring
      parenteral therapy did not significantly differ between study conditions;
      however, during the second year of participant enrolment, the incidence of events
      treated by oral ingestion in the intervention group was 13.6 per 100 person-years
      compared with 27.3 per 100 patient-years in the control group (P = 0.02). The
      hazard ratio of these events during the second year was 0.49 (95% CI 0.27-0.90; P
      = 0.02). CONCLUSIONS: Our findings suggest the need for a long-term (> 1 year)
      focus on the implementation of interventions targeting diabetes management in
      young people. Behavioural interventions targeting problem-solving skills could be
      considered as practical, non-pharmacological strategies to reduce hypoglycaemia
      in adolescents with Type 1 diabetes.

PMID- 25763989
TI  - Membrane protein profiling of Acidovorax avenae subsp. avenae under various
      growth conditions.
AB  - Membrane proteins (MPs) of plant pathogenic bacteria have been reported to be
      able to regulate many essential cellular processes associated with plant disease.
      The aim of the current study was to examine and compare the expression of MPs of
      the rice bacterial pathogen Acidovorax avenae subsp. avenae strain RS-1 under
      Luria-Bertani (LB) medium, M9 medium, in vivo rice plant conditions and leaf
      extract (LE) medium mimicking in vivo plant condition. Proteomic analysis
      identified 95, 72, 75, and 87 MPs under LB, in vivo, M9 and LE conditions,
      respectively. Among them, six proteins were shared under all tested growth
      conditions designated as abundant class of proteins. Twenty-six and 21 proteins
      were expressed uniquely under in vivo versus LB medium and LE versus M9 medium,
      respectively, with 17 proteins common among these uniquely induced proteins.
      Moreover, most of the shared proteins are mainly related to energy metabolism,
      transport of small molecules, protein synthesis and secretion as well as
      virulence such as NADH, OmpA, secretion proteins. Therefore, the result of this
      study not only suggests that it may be an alternate method to analyze the in vivo
      expression of proteins by using LE medium to mimic plant conditions, but also
      reveals that the two sets of differentially expressed MPs, in particular the
      common MPs between them, might be important in energy metabolism, stress response
      and virulence of A. avenae subsp. avenae strain RS-1. 

PMID- 25763990
TI  - Diaphorobacter ruginosibacter sp. nov., isolated from soybean root nodule, and
      emended description of the genus Diaphorobacter.
AB  - A gram-negative bacterium designated BN30(T), which is motile with a polar
      flagellum, non-endospores forming, oxidase- and catalase-positive, was isolated
      from soybean root nodule. The organism is facultative anaerobic and surface
      wrinkled rod. It can grow at 10-40  degrees C, pH 6-8 and 6 % (w/v) NaCl. BLASTn
      search based on 16S rRNA gene sequence revealed that the strain is closely
      related to Diaphorobacter aerolatus 8604S-37(T), Alicycliphilus denitrificans
      K601(T), Simplicispira limi EMB325(T), Diaphorobacter nitroreducens NA10B(T) and
      Diaphorobacter oryzae RF3(T), which all belonged to the family Comamonadaceae in
      class Betaproteobacteria. Phylogenetic analysis showed that the strain formed a
      firm clade with three Diaphorobacter species, being closest to Diaphorobacter
      aerolatus 8604S-37(T) with similarity of 98.64 %. DNA-DNA relatedness values
      between strain BN30(T) and five reference strains ranged from 11.5 to 35.9 %. All
      the results of phylogenetic analysis, chemotaxonomical data (predominant fatty
      acids are C16:0, sum feature 3, sum feature 8 and C17:0 cyclo; major polar lipids
      are diphosphatidylglycerol, phosphatidylethanolamine and phosphatidylglycerol;
      major quinone is Q-8; G+C of total DNA is 65.2 %), physiological and phenotypic
      results supported that BN30(T) represented a novel species within the genus
      Diaphorobacter. The name Diaphorobacter ruginosibacter was proposed, and the type
      strain is BN30(T) (=ACCC06116(T) = DSM 27467(T)). 

PMID- 25763991
TI  - Renal clearance of uric acid is linked to insulin resistance and lower excretion
      of sodium in gout patients.
AB  - Inefficient renal excretion of uric acid is the main pathophysiological mechanism
      for hyperuricemia in gout patients. Polymorphisms of renal tubular transporters
      linked with sodium and monosaccharide transport have yet to be demonstrated. We
      intended to evaluate the impact of insulin resistance, evaluated with the
      homeostasis model assessment (HOMA), through a transversal study of non-diabetic
      patients with gout, with normal renal function, not treated with any medication
      but colchicine as prophylaxis. One hundred and thirty-three patients were
      evaluated. Clearance of uric acid was inversely correlated with insulin
      resistance and directly correlated with fractional excretion of sodium. In
      multivariate analysis, hypertension and hyperlipidemia, in addition to insulin
      resistance and fractional excretion of sodium, were associated with renal
      clearance of uric acid. HOMA cutoff for efficient versus inefficient renal
      handling of uric acid was 2.72, close to that observed in studies of reference
      population. The impact of insulin resistance and renal handling of sodium on
      renal clearance of uric acid may help to explain why hyperuricemia is more
      commonly associated with diabetes and hypertension. 

PMID- 25763992
TI  - Follow-up results of isoniazid chemoprophylaxis during biological therapy in
      Colombia.
AB  - The use of biological therapy has been linked with an increased risk of
      tuberculosis (TB) reactivation. The aim of this study was to present the follow
      up results for isoniazid (INH) chemoprophylaxis in patients receiving different
      biological therapies. In this prospective observational study, patients with
      latent tuberculosis infection (LTBI) were given INH chemoprophylaxis between 2
      and 9 months prior to the beginning of biological therapy. All patients were
      followed up monthly for any signs or symptoms of active TB or INH toxicity. A
      total of 221 patients, 122 females (55.2 %), with a mean age of 46.8 +/- 11.3
      years (16-74) were enrolled. LTBI was identified in 218 patients (98.7 %), all of
      whom received INH chemoprophylaxis. Seven patients (3.2 %) developed active
      tuberculosis, and 32 (17.2 %) patients developed intolerance or toxicity related
      to INH. Chemoprophylaxis with INH seems to be effective and safe for the
      prevention of most TB reactivation in individuals with LTBI, but toxicity must be
      monitored during follow-up.

PMID- 25763993
TI  - Sperm rescue in wild African elephants.
AB  - This study investigated ways of improving the usefulness of ~1700mL of poor
      quality frozen semen collected from wild African elephant (Loxodonta africana)
      bulls. Ten semen samples from six bulls, frozen with 5% glycerol in Berliner
      cryomedium, with or without prior removal of the seminal plasma by
      centrifugation, were tested. All samples were subjected to the following density
      gradient centrifugation treatments: no centrifugation (control), sham
      centrifugation, Percoll, OptiPrep, Isolate and PureSperm. Sample evaluation
      included motility, concentration, viability, acrosome integrity and normal
      morphology after thawing and after gradient centrifugation. Motility was also
      evaluated 3h after thawing. While all treatments were similar to the Control in
      acrosome integrity and normal morphology, significant differences were noted in
      concentration, viability and motility. Samples treated by Percoll showed the best
      motility, which was maintained unchanged over 3h of incubation (37 degrees C).
      Correlations between manual and automated evaluations of concentration were high
      (cytometer; rho=0.92), but were lower for viability (cytometer; rho=0.57) and
      motility (computer-aided sperm analysis; rho=0.66). By performing density
      centrifugation, the quality of these sperm samples may be improved to a level
      suitable for artificial insemination in elephants. Although a sizeable proportion
      of cells are lost in the process, combining samples may still allow for multiple
      inseminations.

PMID- 25763995
TI  - Research education in Europe: an opinion paper by the European Society of
      Radiology.
AB  - Research is a major positive driver for radiology. Therefore, research education
      needs to be a major topic for the radiology leadership, including the research
      committee of the ESR. Professional (radiological and non-radiological) and
      scientific publications as well as Research Committee questionnaires provide the
      basis for this opinion paper. Although radiology is well-positioned to deal with
      current and future challenges, there are still some gaps, such as the presence of
      radiology in basic research, radiology-specific research versus research services
      for other disciplines, need of adaptation to new research topics, general
      attitude towards research, issues of career planning, lack of incentives for
      researchers, gender issues with loss of women from the researcher pipeline,
      limited financing of research education and variability between countries and
      institutions. There is no easy answer to such challenges. However, all
      stakeholders, from the ESR to subspecialty societies, university departments,
      general radiology departments and the individual radiologist must recognise and
      promote research within their competencies. Many means and structures are already
      available but need to be used more extensively and systematically. Additional
      means need to be developed, scientific and professional trends must be actively
      followed, and minimal standards in research education should be maintained
      throughout Europe. Main Messages * Radiology research includes a broad spectrum,
      from basic to health services research. * Research education needs to be widely
      available and systematically promoted. * Existing means such as the European
      Institute for Biomedical Imaging Research (EIBIR) need to be advanced. * New
      developments in research topics and professional life must be continuously
      monitored and evaluated. 

PMID- 25763994
TI  - Medical imaging in personalised medicine: a white paper of the research committee
      of the European Society of Radiology (ESR).
AB  - The future of medicine lies in early diagnosis and individually tailored
      treatments, a concept that has been designated 'personalised medicine' (PM),
      which aims to deliver the right treatment to the right patient at the right time.
      Medical imaging has always been personalised and is fundamental to almost all
      aspects of PM. It is instrumental in solving clinical differential diagnoses.
      Imaging procedures are tailored to the clinical problem and patient
      characteristics. Screening for preclinical disease is done with imaging.
      Stratification based on imaging biomarkers can help identify individuals suited
      for preventive intervention. Treatment decisions are based on the in vivo
      visualisation of the location and extent of an abnormality, as well as the loco
      regional physiological, biochemical and biological processes using structural and
      molecular imaging. Image-guided biopsy provides relevant tissue specimens for
      genetic/molecular characterisation. In addition, radiogenomics relate imaging
      biomarkers to these genetic and molecular features. Furthermore, imaging is
      essential to patient-tailored therapy planning, therapy monitoring and follow-up
      of disease, as well as targeting non-invasive or minimally invasive treatments,
      especially with the rise of theranostics. Radiologists need to be prepared for
      this new paradigm as it will mean changes in training, clinical practice and in
      research. Key Points * Medical imaging is a key component in personalised
      medicine * Personalised prevention will rely on image-based screening programmes
      * Anatomical, functional and molecular imaging biomarkers affect decisions on the
      type and intensity of treatment * Treatment response assessment with imaging will
      improve personalised treatment * Image-based invasive intervention integrates
      personalised diagnosis and personalised treatment. 

PMID- 25763996
TI  - Human metapneumovirus infection activates the TSLP pathway that drives excessive
      pulmonary inflammation and viral replication in mice.
AB  - Human metapneumovirus (hMPV) is a leading cause of acute respiratory tract
      infections in children and the elderly. The mechanism by which this virus
      triggers an inflammatory response still remains unknown. Here, we evaluated
      whether the thymic stromal lymphopoietin (TSLP) pathway contributes to lung
      inflammation upon hMPV infection. We found that hMPV infection promotes TSLP
      expression both in human airway epithelial cells and in the mouse lung. hMPV
      infection induced lung infiltration of OX40L(+) CD11b(+) DCs. Mice lacking the
      TSLP receptor deficient mice (tslpr(-/-) ) showed reduced lung inflammation and
      hMPV replication. These mice displayed a decreased number of neutrophils as well
      a reduction in levels of thymus and activation-regulated chemokine/CCL17, IL-5,
      IL-13, and TNF-alpha in the airways upon hMPV infection. Furthermore, a higher
      frequency of CD4(+) and CD8(+) T cells was found in tslpr(-/-) mice compared to
      WT mice, which could contribute to controlling viral spread. Depletion of
      neutrophils in WT and tslpr(-/-) mice decreased inflammation and hMPV
      replication. Remarkably, blockage of TSLP or OX40L with specific Abs reduced lung
      inflammation and viral replication following hMPV challenge in mice. Altogether,
      these results suggest that activation of the TSLP pathway is pivotal in the
      development of pulmonary pathology and pulmonary hMPV replication. 

PMID- 25763997
TI  - Voluntary Running Attenuates Memory Loss, Decreases Neuropathological Changes and
      Induces Neurogenesis in a Mouse Model of Alzheimer's Disease.
AB  - Alzheimer's disease (AD) is a neurodegenerative disorder characterized by loss of
      memory and cognitive abilities, and the appearance of amyloid plaques composed of
      the amyloid-beta peptide (Abeta) and neurofibrillary tangles formed of tau
      protein. It has been suggested that exercise might ameliorate the disease; here,
      we evaluated the effect of voluntary running on several aspects of AD including
      amyloid deposition, tau phosphorylation, inflammatory reaction, neurogenesis and
      spatial memory in the double transgenic APPswe/PS1DeltaE9 mouse model of AD. We
      report that voluntary wheel running for 10 weeks decreased Abeta burden,
      Thioflavin-S-positive plaques and Abeta oligomers in the hippocampus. In
      addition, runner APPswe/PS1DeltaE9 mice showed fewer phosphorylated tau protein
      and decreased astrogliosis evidenced by lower staining of GFAP. Further, runner
      APPswe/PS1DeltaE9 mice showed increased number of neurons in the hippocampus and
      exhibited increased cell proliferation and generation of cells positive for the
      immature neuronal protein doublecortin, indicating that running increased
      neurogenesis. Finally, runner APPswe/PS1DeltaE9 mice showed improved spatial
      memory performance in the Morris water maze. Altogether, our findings indicate
      that in APPswe/PS1DeltaE9 mice, voluntary running reduced all the
      neuropathological hallmarks of AD studied, reduced neuronal loss, increased
      hippocampal neurogenesis and reduced spatial memory loss. These findings support
      that voluntary exercise might have therapeutic value on AD. 

PMID- 25763998
TI  - Articulatory-to-Acoustic Relations in Talkers With Dysarthria: A First Analysis.
AB  - PURPOSE: The primary purpose of this study was to determine the strength of
      interspeaker and intraspeaker articulatory-to-acoustic relations of vowel
      contrast produced by talkers with dysarthria and controls. METHODS: Six talkers
      with amyotrophic lateral sclerosis (ALS), six talkers with Parkinson's disease
      (PD), and 12 controls repeated a sentence at typical, slow, and fast rates.
      Tongue displacements and acoustic vowel distances were measured to determine
      articulatory and acoustic vowel contrasts. RESULTS: Interspeaker articulatory-to
      acoustic relations were strong for talkers with PD and controls but weak for
      talkers with ALS and controls. Further, predominantly moderate and strong
      intraspeaker articulatory-to-acoustic relations were found in response to rate
      modulations; however, correlation coefficients were significantly lower in
      talkers with ALS than in controls. CONCLUSIONS: The findings on interspeaker
      articulatory-to-acoustic relations suggested that the degree of tongue
      displacement can be accurately inferred from the degree of acoustic vowel
      contrast in talkers with PD but not in talkers with ALS. Findings on intraspeaker
      articulatory-to-acoustic relations generally supported the longstanding notion
      that speaking rate-induced changes in tongue displacement evoke similar changes
      in acoustic vowel contrast. Differential effects of the pathophysiology on inter-
      and intraspeaker articulatory-to-acoustic relations are discussed.

PMID- 25763999
TI  - Evaluation of humoral and cellular immune responses to a DNA vaccine encoding
      chicken type II collagen for rheumatoid arthritis in normal rats.
AB  - A major challenge in the development of effective therapies for rheumatoid
      arthritis (RA) is finding a method for the specific inhibition of the
      inflammatory disease processes without the induction of generalized
      immunosuppression. Of note, the development of therapeutic DNA vaccines and
      boosters that may restore immunological tolerance remains a high priority. pcDNA
      CCOL2A1 is a therapeutic DNA vaccine encoding chicken type II collagen(CCII).
      This vaccine was developed by our laboratory and has been shown to exhibit
      efficacy comparable to that of the current "gold standard" treatment,
      methotrexate (MTX). Here, we used enzyme-linked immunosorbent assays with anti
      CII IgG antibodies, quantified the expression levels of Th1, Th2, and Th3
      cytokines, and performed flow cytometric analyses of different T-cell subsets,
      including Th1, Th2, Th17, Tc, Ts, Treg, and CD4(+)CD29(+)T cells to systemically
      evaluate humoral and cellular immune responses to pcDNA-CCOL2A1 vaccine in normal
      rats. Similar to our observations at maximum dosage of 3 mg/kg, vaccination of
      normal rats with 300 MUg/kg pcDNA-CCOL2A1 vaccine did not induce the production
      of anti-CII IgG. Furthermore, no significant changes were observed in the
      expression levels of pro-inflammatory cytokines interleukin (IL)-1alpha, IL-5, IL
      6, IL-12(IL-23p40), monocyte chemotactic protein (MCP)-1, macrophage inflammatory
      protein (MIP)-1alpha, regulated on activation in normal T-cell expressed and
      secreted (RANTES), receptor activator for nuclear factor-kappaB ligand (RANKL),
      and granulocyte colony-stimulating factor (G-CSF) or anti-inflammatory cytokines
      IL-4 and IL-10 in vaccinated normal rats relative to that in controls(P > 0.05).
      However, transforming growth factor (TGF)-beta levels were significantly
      increased on days 10 and 14, while interferon (IFN)-gamma and tumor necrosis
      factor (TNF)-alpha levels were significantly decreased on days 28 and 35 after
      vaccination(P < 0.05). Similarly, there were no significant differences in the
      percentages of Tc, Ts, Th1/Th2, and Th17 cells between the 2 groups(P > 0.05),
      with the exception of Treg cells, which were significantly reduced on days 14 and
      21 after vaccination (P < 0.05), and CD4(+)CD29(+)T cells, which were
      significantly increased on days 7 and 14 after vaccination(P < 0.05).Taken
      together, these results suggested that pcDNA-CCOL2A1 vaccine did not markedly
      affect the balance of immune system components in vaccinated normal rats,
      indicating that this DNA vaccine may have clinical applications in the treatment
      of RA.

PMID- 25764000
TI  - MicroRNA expression profiling in metastatic cutaneous squamous cell carcinoma.

PMID- 25764001
TI  - The duality of chemokines in heart failure.
AB  - The failing human heart is a bustling network of intra- and inter-cellular
      signals and related processes attempting to coordinate a repair mechanism for the
      injured or diseased myocardium. While our understanding of signaling by mode of
      cytokines is well understood on a systemic level, we are only now coming to
      elucidate the role of cytokines in cardiac self-regulation. An increasing number
      of studies are showing now that cardiomyocytes themselves have not only the
      ability but also the mandate to produce signals, and play direct roles in how
      these signals are interpreted. One of the families of cytokines employed by
      distressed cardiac tissue are chemokines. By regulating the movement of pro
      inflammatory cell types to sites of injury, we see now how the myocardium
      responds to stress. Herein we review the participation of these inflammatory
      mediators and explore the delicate balance between their protective roles and
      damaging functions. 

PMID- 25764002
TI  - Surgical treatment of congenital patellar dislocation in skeletally mature
      patients: surgical technique and case series.
AB  - BACKGROUND: Congenital patellar dislocation is a rarely encountered condition and
      is readily treated in childhood to prevent lasting disability, knee pain,
      decreased range of motion and ambulation problems. This condition is very rarely
      seen in skeletally mature patients, and the treatment of the condition represents
      a challenge to the orthopedic surgeon. SURGICAL TECHNIQUE AND METHODS: Patients
      were treated with soft tissue reconstruction and tibial tubercle transfer with or
      without a prior medial close-wedge distal femoral osteotomy, depending on the
      degree of valgus deformity. We, then, searched the database of our orthopedics
      center for cases of congenital patellar dislocation in skeletally mature patients
      who were surgically treated. We collected a total of five knees and analyzed the
      cases according to the type of surgery performed and difference between pre- and
      postoperative functions. RESULTS: Five knees with congenital patellar dislocation
      were treated. The mean age of the patients was 29.6 years, and mean follow-up
      time was 4.3 years. Mean preoperative range of motion was 65 degrees , and it
      increased to a mean of 105.5 degrees  after surgical treatment. The mean
      preoperative Kujala score was 29.2 and increased to 67.2 after surgical
      treatment. DISCUSSION: Congenital patellar dislocations that are allowed to
      proceed to adulthood are difficult to treat, and surgical treatment depends on
      the degree of deformity of the patella and of the knee joint. This study shows
      that surgical treatment is able to correct the deformity and provide better knee
      function.

PMID- 25764003
TI  - Characterization of genomic alterations in radiation-associated breast cancer
      among childhood cancer survivors, using comparative genomic hybridization (CGH)
      arrays.
AB  - Ionizing radiation is an established risk factor for breast cancer. Epidemiologic
      studies of radiation-exposed cohorts have been primarily descriptive; molecular
      events responsible for the development of radiation-associated breast cancer have
      not been elucidated. In this study, we used array comparative genomic
      hybridization (array-CGH) to characterize genome-wide copy number changes in
      breast tumors collected in the Childhood Cancer Survivor Study (CCSS). Array-CGH
      data were obtained from 32 cases who developed a second primary breast cancer
      following chest irradiation at early ages for the treatment of their first
      cancers, mostly Hodgkin lymphoma. The majority of these cases developed breast
      cancer before age 45 (91%, n = 29), had invasive ductal tumors (81%, n = 26),
      estrogen receptor (ER)-positive staining (68%, n = 19 out of 28), and high
      proliferation as indicated by high Ki-67 staining (77%, n = 17 out of 22).
      Genomic regions with low-copy number gains and losses and high-level
      amplifications were similar to what has been reported in sporadic breast tumors,
      however, the frequency of amplifications of the 17q12 region containing human
      epidermal growth factor receptor 2 (HER2) was much higher among CCSS cases (38%,
      n = 12). Our findings suggest that second primary breast cancers in CCSS were
      enriched for an "amplifier" genomic subgroup with highly proliferative breast
      tumors. Future investigation in a larger irradiated cohort will be needed to
      confirm our findings. 

PMID- 25764004
TI  - Factors associated with resistant hypertension in a large cohort of hypertensive
      patients: the Pol-Fokus study.
AB  - INTRODUCTION:  Patients with resistant hypertension (RHT) are at high risk for
      coronary artery disease (CAD) and cerebrovascular disease (CVD), compared with
      the general hypertensive population. OBJECTIVES:  The aim of the study was to
      evaluate factors associated with RHT in a large sample of hypertensive patients
      under the care of general practitioners and specialists in Poland. PATIENTS AND
      METHODS:  We included 12 375 patients (mean age, 64.0 +/-12.3 years; age range,
      18-98 years; women, 59%) with hypertension treated for at least 1 year. Patients
      were divided into 3 groups: with controlled hypertension, uncontrolled
      hypertension (not fulfilling the criteria for RHT), and RHT. RESULTS:  Controlled
      hypertension, uncontrolled hypertension, and RHT were found in 47.3%, 27.9%, and
      24.7% of the patients, respectively. The RHT rate was higher in patients visiting
      specialist offices (29.8%) and in patients with diabetes (32.5%), CAD (31.5%),
      CVD (33.3%), and impaired renal function (31.9%). Patients with RHT were
      characterized by the highest rate of high (23.5%) and very high (60.5%) added
      cardiovascular risk. An underuse of preferred antihypertensive drug combinations
      and aldosterone antagonists in patients with uncontrolled hypertension and RHT
      was observed. In a multivariate analysis, RHT was independently associated with
      male sex, higher pulse pressure, metabolic syndrome, diabetes, CAD, CVD, diseases
      requiring treatment with nonsteroidal anti-inflammatory drugs and an estimated
      glomerular filtration rate of less than 60 ml/min/1.73 m2. CONCLUSIONS:  The vast
      majority of patients with RHT carry a high or very high cardiovascular risk. In
      addition, the underuse of preferred antihypertensive drug combinations and
      aldosterone antagonists has been observed.

PMID- 25764005
TI  - Correction: survival and biodistribution of xenogenic adipose mesenchymal stem
      cells is not affected by the degree of inflammation in arthritis.

PMID- 25764008
TI  - Allergen relative abundance in several wheat varieties as revealed via a targeted
      quantitative approach using MS.
AB  - Food allergy has become a major health issue in developed countries, therefore
      there is an urgent need to develop analytical methods able to detect and quantify
      with a good sensitivity and reliability some specific allergens in complex food
      matrices. In this paper, we present a targeted MS/MS approach to compare the
      relative abundance of the major recognized wheat allergens in the salt-soluble
      (albumin/globulin) fraction of wheat grains. Twelve allergens were quantified in
      seven wheat varieties, selected from three Triticum species: T. aestivum (bread
      wheat), T. durum (durum wheat), and T. monococcum. The allergens were monitored
      from one or two proteotypic peptides and their relative abundance was deduced
      from the intensity of one fragment measured in MS/MS. Whereas the abundance of
      some of the targeted allergens was quite stable across the genotypes, others like
      alpha-amylase inhibitors showed clear differences according to the wheat species,
      in accordance with the results of earlier functional studies. This study enriches
      the scarce knowledge available on allergens content in wheat genotypes, and
      brings new perspectives for food safety and plant breeding. 

PMID- 25764006
TI  - Psychiatric consultation to the postpartum mother.
AB  - The immediate postpartum period is a time of acute vulnerability to mental
      illness, which presents unique challenges for the psychiatric consultant. Because
      the postpartum hospital stay is typically brief, the consultant must have a
      working knowledge of postpartum physiology and the myriad forms of mental illness
      that may emerge in this vulnerable time, in order to quickly make a diagnosis and
      formulate a treatment plan. This review aims to characterize the most common
      reasons for postpartum consultation, review postpartum physiology and psychiatric
      conditions, and propose an evidence-based, practical approach to treatment. A
      literature search using the terms "postpartum," "obstetric," "consultation," and
      "psychiatry" yielded six studies that identified reasons for psychiatric
      consultation to the obstetrics and gynecology services. These studies informed
      the structure of the article such that we review the most common reasons for
      consultation and how to approach each issue. The most common reason for
      consultation is past psychiatric history, often in the absence of current
      symptoms. For each clinical situation, including depression, adverse birth
      events, and psychosis, we present a differential diagnosis, as well as risk
      factors, clinical signs, and recommended treatment. 

PMID- 25764010
TI  - Prognostic factors affecting survival in non-small cell lung carcinoma patients
      with malignant pleural effusions.
AB  - BACKGROUND AND AIMS: Lung cancer is the most common cause of malignant pleural
      effusions (MPEs). For patients with lung cancer and MPE, median survival is only
      3-4 months. The aim of this study was to evaluate lung cancer patients with MPE
      by clinical and laboratory findings on admission, and determine 2-year survival
      rate and prognostic factors. METHODS: Between 2008 and 2011, we examined 199
      cases of non-small cell lung carcinoma with MPE. Demographic factors of patients,
      tumor characteristics, treatment delivered and laboratory parameters affecting
      prognosis were evaluated. Survival rates were estimated by Kaplan-Meier method.
      Significance of each prognostic factors selected by univariate analysis were
      confirmed using Cox regression model. RESULTS: The study included 139 (69.8%)
      male and 60 (30.2%) female patients with a median age of 64 (30-85) years. Median
      overall survival was 4.4 months. Adenocarcinoma was the leading cause of MPE with
      80.4%. A univariate analysis showed that factors affecting mortality included
      gender (P < 0.001), MPE with distant metastasis (P = 0.025), lower serum albumin
      (P < 0.0001), lower pleural protein (P < 0.0001), increased serum lactate
      dehydrogenase (P = 0.003), increased serum C-reactive protein (CRP) (P < 0.0001),
      increased white blood cells (P < 0.0001), histopathological type (P = 0.004) and
      treatment decision (P < 0.0001). A multivariate analysis revealed that patients
      who had high level of serum CRP (P = 0.017), lower serum albumin (P = 0.009) and
      lower pleural protein (P = 0.003), MPE with distant metastasis (P = 0.003) and
      those who were chemotherapy naive (P < 0.0001) had shorter survival. CONCLUSION:
      High level of serum CRP, lower serum albumin and lower pleural protein, MPE with
      distant metastasis were most important prognostic factors for non-small cell lung
      carcinoma in patients with MPEs.

PMID- 25764009
TI  - Impact of eNOS-Dependent Oxidative Stress on Endothelial Function and Neointima
      Formation.
AB  - AIMS: Vascular oxidative stress generated by endothelial NO synthase (eNOS) was
      observed in experimental and clinical cardiovascular disease, but its relative
      importance for vascular pathologies is unclear. We investigated the impact of
      eNOS-dependent vascular oxidative stress on endothelial function and on
      neointimal hyperplasia. RESULTS: A dimer-destabilized mutant of bovine eNOS where
      cysteine 101 was replaced by alanine was cloned and introduced into an eNOS
      deficient mouse strain (eNOS-KO) in an endothelial-specific manner.
      Destabilization of mutant eNOS in cells and eNOS-KO was confirmed by the reduced
      dimer/monomer ratio. Purified mutant eNOS and transfected cells generated less
      citrulline and NO, respectively, while superoxide generation was enhanced. In
      eNOS-KO, introduction of mutant eNOS caused a 2.3-3.7-fold increase in superoxide
      and peroxynitrite formation in the aorta and myocardium. This was completely
      blunted by an NOS inhibitor. Nevertheless, expression of mutant eNOS in eNOS-KO
      completely restored maximal aortic endothelium-dependent relaxation to
      acetylcholine. Neointimal hyperplasia induced by carotid binding was much larger
      in eNOS-KO than in mutant eNOS-KO and C57BL/6, while the latter strains showed
      comparable hyperplasia. Likewise, vascular remodeling was blunted in eNOS-KO
      only. INNOVATION: Our results provide the first in vivo evidence that eNOS
      dependent oxidative stress is unlikely to be an initial cause of impaired
      endothelium-dependent vasodilation and/or a pathologic factor promoting intimal
      hyperplasia. These findings highlight the importance of other sources of vascular
      oxidative stress in cardiovascular disease. CONCLUSION: eNOS-dependent oxidative
      stress is unlikely to induce functional vascular damage as long as concomitant
      generation of NO is preserved. This underlines the importance of current and new
      therapeutic strategies in improving endothelial NO generation.

PMID- 25764011
TI  - Understanding the Implications of Mitochondrial DNA Variation in the Health of
      Black Southern African Populations: The 2014 Workshop.

PMID- 25764013
TI  - Water dispersion interactions strongly influence simulated structural properties
      of disordered protein states.
AB  - Many proteins can be partially or completely disordered under physiological
      conditions. Structural characterization of these disordered states using
      experimental methods can be challenging, since they are composed of a
      structurally heterogeneous ensemble of conformations rather than a single
      dominant conformation. Molecular dynamics (MD) simulations should in principle
      provide an ideal tool for elucidating the composition and behavior of disordered
      states at an atomic level of detail. Unfortunately, MD simulations using current
      physics-based models tend to produce disordered-state ensembles that are
      structurally too compact relative to experiments. We find that the water models
      typically used in MD simulations significantly underestimate London dispersion
      interactions, and speculate that this may be a possible reason for these
      erroneous results. To test this hypothesis, we create a new water model, TIP4P-D,
      that approximately corrects for these deficiencies in modeling water dispersion
      interactions while maintaining compatibility with existing physics-based models.
      We show that simulations of solvated proteins using this new water model
      typically result in disordered states that are substantially more expanded and in
      better agreement with experiment. These results represent a significant step
      toward extending the range of applicability of MD simulations to include the
      study of (partially or fully) disordered protein states. 

PMID- 25764012
TI  - Landscape of chromosomal copy number aberrations in gangliogliomas and
      dysembryoplastic neuroepithelial tumours.
AB  - AIM: Gangliogliomas (GGs) and dysembryoplastic neuroepithelial tumours (DNTs)
      represent the most common histological entities within the spectrum of
      glioneuronal tumours (GNTs). The wide variability of morphological features
      complicates histological classification, including discrimination from
      prognostically distinct diffuse low-grade astrocytomas (AIIs). This study was
      performed to increase our understanding of these tumours. METHODS: We studied
      chromosomal copy number aberrations (CNAs) by genome-wide sequencing in a large
      cohort of GNTs and linked these to comprehensive histological analysis and
      clinical characteristics. One hundred fourteen GNTs were studied: 50 GGs and 64
      DNTs. Also, a data set of CNAs from 38 diffuse AIIs was included. RESULTS: The
      most frequent CNAs in both GGs and DNTs were gains at chromosomes 5 and 7, often
      concurrent, and gain at chromosome 6. None of the CNAs was linked to histological
      subtype, immunohistochemical features or to clinical characteristics. Comparison
      of AIIs and diffuse GNTs revealed that gain at whole chromosome 5 is only
      observed in GNTs. CNA patterns indicative of chromothripsis were detected in
      three GNTs. CONCLUSION: We conclude that GNTs with diverse morphologies share
      molecular features, and our findings support the need to improve classification
      and differential diagnosis of tumour entities within the spectrum of GNTs, as
      well as their distinction from other gliomas.

PMID- 25764014
TI  - Non-fatal Lithium Intoxication with 5.5 mmol/L Serum Level.

PMID- 25764015
TI  - Up-converted fluorescence from photosynthetic light-harvesting complexes linearly
      dependent on excitation intensity.
AB  - Weak up-converted fluorescence related to bacteriochlorophyll a was recorded from
      various detergent-isolated and membrane-embedded light-harvesting pigment-protein
      complexes as well as from the functional membranes of photosynthetic purple
      bacteria under continuous-wave infrared laser excitation at 1064 nm, far outside
      the optically allowed singlet absorption bands of the chromophore. The
      fluorescence increases linearly with the excitation power, distinguishing it from
      the previously observed two-photon excited fluorescence upon femtosecond pulse
      excitation. Possible mechanisms of this excitation are discussed.

PMID- 25764016
TI  - Violaxanthin de-epoxidase disulphides and their role in activity and thermal
      stability.
AB  - Violaxanthin de-epoxidase (VDE) catalyses the conversion of violaxanthin to
      zeaxanthin at the lumen side of the thylakoids during exposure to intense light.
      VDE consists of a cysteine-rich N-terminal domain, a lipocalin-like domain and a
      negatively charged C-terminal domain. That the cysteines are important for the
      activity of VDE is well known, but in what way is less understood. In this study,
      wild-type spinach VDE was expressed in E. coli as inclusion bodies, refolded and
      purified to give a highly active and homogenous preparation. The metal content
      (Fe, Cu, Ni, Mn, Co and Zn) was lower than 1 mol% excluding a metal-binding
      function of the cysteines. To investigate which of the 13 cysteines that could be
      important for the function of VDE, we constructed mutants where the cysteines
      were replaced by serines, one by one. For 12 out of 13 mutants the activity
      dropped by more than 99.9%. A quantification of free cysteines showed that only
      the most N-terminal of these cysteines was in reduced form in the native VDE. A
      disulphide pattern in VDE of C9-C27, C14-C21, C33-C50, C37-C46, C65-C72 and C118
      C284 was obtained after digestion of VDE with thermolysin followed by mass
      spectroscopy analysis of reduced versus non-reduced samples. The residual
      activity found for the mutants showed a variation that was consistent with the
      results obtained from mass spectroscopy. Reduction of the disulphides resulted in
      loss of a rigid structure and a decrease in thermal stability of 15  degrees C.

PMID- 25764018
TI  - Role for risk-scoring tools in identifying resistant pathogens in pneumonia:
      reassessing the value of healthcare-associated pneumonia as a concept.
AB  - PURPOSE OF REVIEW: Resistant organisms remain a concern in patients presenting to
      hospital with pneumonia. Although in this setting the prevalence of various
      organisms such as methicillin-resistant Staphylococcus aureus and Pseudomonas
      aeruginosa varies across the globe, patients infected with these pathogens are at
      increased risk for receiving an initially inappropriate antibiotic regimen - a
      major driver of mortality in all forms of pneumonia. The concept of healthcare
      associated pneumonia (HCAP) was created to help clinicians identify persons at
      risk for infection with resistant pathogens, despite the onset of their
      infections occurring outside the hospital. However, it appears that HCAP, as
      currently defined, lacks adequate sensitivity and specificity for this purpose.
      RECENT FINDINGS: Investigators have created various risk-scoring tools to
      stratify patients as to the likelihood that their infection is caused by a
      pathogen such as methicillin-resistant S. aureus or P. aeruginosa. These scores
      provide more precision at correctly segregating patients on the basis of the
      eventual recovery of resistant bacteria than does the HCAP syndrome. Most of
      these risk scores are easy to calculate and apply, and several have been
      externally validated. SUMMARY: Physicians should consider adopting these tools in
      their approach to patients with pneumonia presenting to hospital.

PMID- 25764017
TI  - Efficacy and safety of deferasirox estimated by serum ferritin and labile plasma
      iron levels in patients with aplastic anemia, myelodysplastic syndrome, or acute
      myeloid leukemia with transfusional iron overload.
AB  - BACKGROUND: Patients receiving red blood cell (RBC) transfusions are at risk of
      iron overload, which can cause significant organ damage and is an important cause
      of morbidity and mortality. STUDY DESIGN AND METHODS: This study was an open
      label, single-arm, prospective clinical study to evaluate the efficacy and safety
      of deferasirox (DFX) in patients with aplastic anemia (AA), myelodysplastic
      syndrome (MDS), or acute myeloid leukemia (AML). Patients with serum ferritin
      levels of at least 1000 ng/mL and ongoing transfusion requirements were enrolled.
      DFX was administered for up to 1 year. A total of 100 patients were enrolled.
      RESULTS: Serum ferritin levels decreased significantly following treatment (from
      2000 to 1650 ng/mL, p = 0.004). The median absolute reduction in serum ferritin
      levels was -65 ng/mL in AA (p = 0.037), -647 ng/mL in lower-risk MDS (MDS-LR; p =
      0.007), and -552 ng/mL in higher-risk MDS (MDS-HR)/AML (p = 0.482). Mean labile
      plasma iron (LPI) levels decreased from 0.24 MUmol/L at baseline to 0.03 MUmol/L
      at 1 year in all patients (p = 0.036). The mean LPI reduction in each group was 
      0.17 MUmol/L in AA, -0.21 MUmol/L in MDS-LR, and -0.30 MUmol/L in MDS-HR/AML.
      Gastrointestinal disorders were commonly observed among groups (16.0%). DFX was
      temporarily skipped for adverse events in seven patients (7.0%) and was
      permanently discontinued in 11 patients (11.0%). CONCLUSION: DFX reduced serum
      ferritin and LPI levels in patients with transfusional iron overload. Despite the
      relatively high percentage of gastrointestinal side effects, DFX was tolerable in
      all subgroups.

PMID- 25764019
TI  - Bronchiectasis: which antibiotics to use and when?
AB  - PURPOSE OF REVIEW: In 2010, the British Thoracic Society published a guideline
      for the care of patients with noncystic fibrosis (non-CF) bronchiectasis; other
      recent clinical review articles and original scientific manuscripts have also
      studied the use of antibiotics in bronchiectasis. This review will summarize the
      current literature on the indications and options for antibiotic treatment in
      bronchiectasis. RECENT FINDINGS: Since 2012, a number of manuscripts have been
      published that provide evidence to support the use of antibiotics in non-CF
      bronchiectasis, including macrolide antibiotics, inhaled aminoglycosides and
      inhaled fluoroquinolone therapies. However, data remain preliminary and there are
      phase 3 trials underway to further investigate the efficacy and safety of
      antibiotics in non-CF bronchiectasis. SUMMARY: Although there are currently no
      U.S. Food and Drug Administration (FDA)-approved antibiotics for the treatment of
      patients with bronchiectasis, this review will highlight the current state of the
      science with regard to antibiotics that may be effective in non-CF bronchiectasis
      as well as highlighting those in development to treat this complex disease.

PMID- 25764020
TI  - Impact of the Xpert MTB/RIF diagnostic test for tuberculosis in countries with a
      high burden of disease.
AB  - PURPOSE OF REVIEW: Control of tuberculosis necessitates prompt diagnosis and
      access to effective treatment. We discuss the impact of a new nucleic acid
      amplification test to assist diagnosis and detect rifampicin resistance.
      Following encouraging clinical performance studies, an automated PCR-based test,
      the Xpert MTB/RIF (Cepheid, Sunnyvale, CA), has been implemented on a global
      scale. Clinical trials to assess the impact of the new technology in primary
      healthcare clinics have been undertaken in tuberculosis (TB) endemic countries.
      RECENT FINDINGS: Clinical trials at the point of care in TB endemic countries
      demonstrated that increased numbers of TB patients are identified using the Xpert
      MTB/RIF assay as the frontline diagnostic test in place of sputum smear
      microscopy. Decreased times from sample collection to initiation of treatment
      were also reported when using the molecular test. However, overall case
      notification rates did not improve, and no significant impact on patient outcome
      (morbidity or mortality) was reported. SUMMARY: Sensitive molecular tests to
      assist diagnosis of tuberculosis may provide a faster diagnostic result when used
      in clinics and laboratories, but the limited impact on patient outcomes suggests
      additional interventions are needed to enhance TB control.

PMID- 25764021
TI  - Emerging respiratory tract viral infections.
AB  - PURPOSE OF REVIEW: This article reviews the clinical and treatment aspects of
      avian influenza viruses and the Middle East Respiratory Syndrome coronavirus
      (MERS-CoV). RECENT FINDINGS: Avian influenza A(H5N1) and A(H7N9) viruses have
      continued to circulate widely in some poultry populations and infect humans
      sporadically. Sporadic human cases of avian A(H5N6), A(H10N8) and A(H6N1) have
      also emerged. Closure of live poultry markets in China has reduced the risk of
      A(H7N9) infection. Observational studies have shown that oseltamivir treatment
      for adults hospitalized with severe influenza is associated with lower mortality
      and better clinical outcomes, even as late as 4-5 days after symptom onset.
      Whether higher than standard doses of neuraminidase inhibitor would provide
      greater antiviral effects in such patients requires further investigation. High
      dose systemic corticosteroids were associated with worse outcomes in patients
      with A(H1N1)pdm09 or A(H5N1). MERS-CoV has continued to spread since its first
      discovery in 2012. The mortality rates are high in those with comorbid diseases.
      There is no specific antiviral treatment or vaccine available. The exact mode of
      transmission from animals to humans remains unknown. SUMMARY: There is an urgent
      need for developing more effective antiviral therapies to reduce morbidity and
      mortality of these emerging viral respiratory tract infections.

PMID- 25764022
TI  - Improving outcomes from community-acquired pneumonia.
AB  - PURPOSE OF REVIEW: We are entering into a new era of healthcare wherein patient
      outcomes are increasingly being publicly reported, not just by institution, but
      by individual clinicians. This review focuses on the issue of quality of care of
      patients with community-acquired pneumonia (CAP), in particular the choice of
      outcome, quality of data needed and recommendations of the current bundle of care
      suggested by the available literature as delivering the best chance of favourable
      outcomes for patients. RECENT FINDINGS: There is increasing evidence that
      pneumonia outcomes have improved over the past decade, particularly mortality.
      However, we have been oversimplistic in setting quality targets and that a bundle
      of care is required to deliver best outcomes, such as has been shown with the
      surviving sepsis campaign. Equally, the quality of data available to compare
      outcomes needs to be significantly improved on what is currently available.
      SUMMARY: To achieve best outcomes for their patients, physicians must be actively
      comparing their outcomes against other institutions and not rely on historical
      data. A bundle of care that includes rapid administration of antibiotics, use of
      combination antibiotic therapy including a macrolide and early mobilization is a
      good starting point.

PMID- 25764023
TI  - Exploring the skin-to-skin contact experience during cesarean section.
AB  - PURPOSE: To explore and describe the mother's experience of holding her neonate
      in skin-to-skin contact (SSC) immediately after cesarean delivery during surgical
      closure and recovery. DATA SOURCES: Eleven women between the ages of 23 and 38
      years, who had achieved 39.1-40.2 weeks gestational age, participated in an
      ethnographic study using observations and interviews with the mothers conducted
      at 24-48 h postdelivery. Interviews were transcribed verbatim and content
      analysis of both observational notes and transcripts were used to analyze the
      data. CONCLUSIONS: Findings from this study describe the mother's experience of
      SSC during cesarean section. The primary theme that emerged was mutual
      caregiving: the mother-neonatal interaction and their shared and reciprocal
      relationship and benefits during SSC. Two contextual issues also were illuminated
      (a) the father's influence on the SSC experience and (b) the cesarean
      environment. IMPLICATIONS FOR PRACTICE: With cesarean section the most common
      surgical procedure among American women, advanced practice nurses are in a unique
      position to encourage and educate women on the use of SSC for their benefit and
      that of their newborn. Advanced practice nurses are also empowered to influence
      institutional policy on SSC during cesarean deliveries at the local and national
      level.

PMID- 25764024
TI  - The influence of telemedicine experience on physicians' perceptions regarding
      adoption.
AB  - BACKGROUND: The purposes of this study were to explore the factors influencing
      physicians' intention of adopting telemedicine and to conduct a multigroup
      analysis comparing the perceptions about telemedicine adoption between
      experienced and inexperienced physicians. Based on the Theory of Planned
      Behavior, we conducted a cross-sectional survey to collect data from 15 hospitals
      in Taiwan. MATERIALS AND METHODS: In total, 106 valid questionnaires were
      returned. We used structural equation modeling to analyze the collected data.
      RESULTS: Attitude (AT), subjective norm (SN), and perceived behavioral control
      (PBC) were found to be positively related to behavioral intention (BI) for
      combined data. Moreover, the relationships between AT->BI, SN->BI, and PBC->BI
      varied significantly between experienced and inexperienced physicians.
      Experienced physicians held stronger beliefs about the relationship between AT
      >BI than inexperienced physicians. CONCLUSIONS: According to the results, our
      study suggests that differing strategies for experienced and inexperienced
      physicians must be formulated to substantially boost the adoption of telemedicine
      technology.

PMID- 25764025
TI  - Abstracts of the 94th Annual Meeting of the German Physiological Society, 5-7
      March, 2015, Madgeburg, Germany.

PMID- 25764026
TI  - Prognostic role of nuclear factor/IB and bone remodeling proteins in metastatic
      giant cell tumor of bone: A retrospective study.
AB  - Giant cell tumor of bone (GCTb) represents 5% of bone tumors, and although
      considered benign, 5% metastasize to the lung. The expression of proteins
      directly or indirectly associated with osteolysis and tumor growth was studied on
      163 samples of GCTb. Of these, 33 patients developed lung metastasis during
      follow-up. The impact of tumor-host interaction on clinical aspects was evaluated
      with the aim of finding specific markers for new biological therapies, thus
      improving clinical management of GCTb. Protein expression was evaluated by
      immunohistochemical analysis on Tissue Microarray. The majority of GCTb samples
      from patients with metastatic disease were strongly positive to RANKL and its
      receptor RANK as well as to CAII and MMP-2 and to pro-survival proteins NFIB and
      c-Fos. Kaplan-Meier analysis indicated a significant difference in metastasis
      free survival curves based on protein staining. Interestingly, the statistical
      correlation established a strong association between all variables studied with a
      higher tau coefficient for RANK/RANKL, RANK/NFIB, and RANKL/NFIB pairs. At
      multivariate analysis co-overexpression of NFIB, RANK and RANKL significantly
      increased the risk of metastasis with an odds ratio of 13.59 (95%CI 4.12-44.82; p
      < 0.0005). In conclusion, the interconnection between matrix remodeling and tumor
      cell activity may identify tumor-host endpoints for new biological treatments.

PMID- 25764028
TI  - Suction avulsion of the fallopian tube during surgical abortion.

PMID- 25764029
TI  - Balance.

PMID- 25764027
TI  - The complex contributions of genetics and nutrition to immunity in Drosophila
      melanogaster.
AB  - Both malnutrition and undernutrition can lead to compromised immune defense in a
      diversity of animals, and "nutritional immunology" has been suggested as a means
      of understanding immunity and determining strategies for fighting infection. The
      genetic basis for the effects of diet on immunity, however, has been largely
      unknown. In the present study, we have conducted genome-wide association mapping
      in Drosophila melanogaster to identify the genetic basis for individual variation
      in resistance, and for variation in immunological sensitivity to diet (genotype
      by-environment interaction, or GxE). D. melanogaster were reared for several
      generations on either high-glucose or low-glucose diets and then infected with
      Providencia rettgeri, a natural bacterial pathogen of D. melanogaster. Systemic
      pathogen load was measured at the peak of infection intensity, and several
      indicators of nutritional status were taken from uninfected flies reared on each
      diet. We find that dietary glucose level significantly alters the quality of
      immune defense, with elevated dietary glucose resulting in higher pathogen loads.
      The quality of immune defense is genetically variable within the sampled
      population, and we find genetic variation for immunological sensitivity to
      dietary glucose (genotype-by-diet interaction). Immune defense was genetically
      correlated with indicators of metabolic status in flies reared on the high
      glucose diet, and we identified multiple genes that explain variation in immune
      defense, including several that have not been previously implicated in immune
      response but which are confirmed to alter pathogen load after RNAi knockdown. Our
      findings emphasize the importance of dietary composition to immune defense and
      reveal genes outside the conventional "immune system" that can be important in
      determining susceptibility to infection. Functional variation in these genes is
      segregating in a natural population, providing the substrate for evolutionary
      response to pathogen pressure in the context of nutritional environment. 

PMID- 25764030
TI  - Moving goals and policy into effective action for mothers and newborns around the
      world: the mother- and baby-friendly hospital initiative.

PMID- 25764031
TI  - Kielland's forceps: demise before the 100th anniversary?

PMID- 25764032
TI  - Assessing the incremental value of blood oxygen saturation (SpO(2)) in the
      miniPIERS (Pre-eclampsia Integrated Estimate of RiSk) Risk Prediction Model.
AB  - OBJECTIVE: To assess the incremental value of blood oxygen saturation (SpO(2)) as
      a predictor in the miniPIERS model, a risk prediction model for adverse outcomes
      among women with a diagnosis of hypertensive disorder of pregnancy (HDP) in low
      resourced settings. METHODS: Using data from a prospective cohort including 852
      women admitted to hospital for a HDP, the association between SpO(2) and adverse
      maternal outcome was assessed using logistic regression. The miniPIERS model was
      recalibrated and extended to include SpO(2). The incremental value of adding
      SpO(2) to the model was measured using a net reclassification index (NRI),
      sensitivity, specificity, positive and negative predictive values, and likelihood
      ratios. RESULTS: SpO(2) of < 93% was associated with a 30-fold increase in risk
      (95% CI 14 to 68) of adverse maternal outcome compared to women with SpO(2) >
      97%. After recalibration and extension, the miniPIERS model including SpO(2) (vs.
      not including SpO(2)) had improved sensitivity (32.8% vs. 49.6%) at the cost of
      minimally decreased specificity (91.5% vs. 96.2%) with a NRI of 0.122.
      CONCLUSION: SpO(2) is a significant independent predictor of risk in women with a
      HDP. Adding SpO(2) to the miniPIERS model improved the model's ability to
      correctly identify high-risk patients who would benefit most from interventions.

PMID- 25764033
TI  - Obstetrical complications in pregnant medical and surgical residents.
AB  - OBJECTIVE: Pregnant residents are at risk for obstetrical complications. The
      purpose of our study was to evaluate the incidence and type of obstetrical
      complications of pregnancy during residency training, and their possible
      contributing factors. METHOD: We conducted a retrospective cohort study using a
      web-based questionnaire sent to 190 residency programs, both medical and
      surgical, across North America. The questionnaire was distributed to all female
      residents, and participants were asked to answer the questionnaire only if they
      had ever been pregnant. The questionnaire consisted of 10 multiple-choice
      questions and focused mainly on the complications that residents may have
      encountered during pregnancy before and during their residency training. The
      results were compared with those of 3767 pregnant women of similar age. RESULTS:
      The rate of obstetrical complications among residents who had up to six nights on
      call per month (43/163 or 26.4%) was significantly lower than those who had more
      than six nights on call per month (37/75 or 49.3%) (P < 0.001). Among surgical
      residents, 16% performed over 40 hours of surgery per week. The rate of
      obstetrical complications among residents who had up to eight hours of operating
      room time per week (8.9%) was significantly lower than among residents who worked
      more than eight hours per week (41.7%) (P < 0.001). When we compared obstetrical
      complications among residents with those of women in the general population, we
      found that residents had higher rates of miscarriage, hypertension in pregnancy,
      placental abruption, and intrauterine growth restriction. CONCLUSION: Pregnancy
      during residency has a higher than average rate of adverse obstetrical outcomes.
      Longer operating hours and having more than six nights on call per month are
      associated with obstetrical complications. In addition, pregnant residents are
      more likely to have hypertensive disorders of pregnancy, intrauterine growth
      restriction, placental abruption, and miscarriages than a cohort of pregnant
      women of similar age.

PMID- 25764034
TI  - Smoking cessation during pregnancy and relapse after childbirth in Canada.
AB  - OBJECTIVE: This analysis was undertaken to determine the rates and determinants
      of smoking cessation during pregnancy and smoking relapse after childbirth in
      Canada. METHODS: We used data from the Maternity Experiences Survey, a cross
      sectional study of mothers who gave birth to a singleton baby in Canada in 2006.
      A total of 1586 mothers who smoked occasionally or daily before pregnancy were
      included in the analysis. RESULTS: The rate of smoking cessation during pregnancy
      was 53.0% (95% CI 50.3% to 55.7%). Higher pre-pregnancy smoking frequency, Inuit
      origin, being aged >= 35 years, lower education, not attending prenatal classes,
      lack of social support, stress before or during pregnancy, and living with a
      smoker were independently associated with higher risk of continued smoking, while
      First Nations (off-reserve) origin was associated with a lower risk. Among those
      who had quit smoking, 47.1% (95% CI 43.5% to 50.6%) relapsed postpartum. Living
      with a smoker, not having breastfed, and having stopped breastfeeding were
      independently associated with a higher risk of relapse. CONCLUSION: This study
      highlights the need to tailor smoking cessation and prevention interventions for
      some high-risk groups of women.

PMID- 25764035
TI  - Determinants of late presentation for induced abortion care.
AB  - OBJECTIVE: To determine whether demographic or patient factors contribute to
      later presentation (10 to 12 weeks' gestational age) for induced abortion in a
      Canadian abortion clinic. METHODS: Women attending a hospital-based abortion
      clinic between April and September 2012 were asked to complete a survey. The
      characteristics of women who presented early (EPs; gestational age < 10 weeks)
      were compared with those of late presenters (LPs; gestational age >= 10 weeks)
      using t tests for means and Fisher exact tests for rates. RESULTS: Among women
      referred to the clinic by a primary care provider, LPs were more likely than EPs
      to report "a delay in obtaining a referral" (20.8% vs. 6.1%; P = 0.007). While
      there was no significant difference between the groups in reporting that "someone
      tried to discourage [them] from having an abortion" (26.45% for EPs, 32.4% for
      LPs; P = 0.421), LPs were more likely to report that discouragement "caused a
      delay in making arrangements" (45.5% vs. 16.7%; P = 0.019). Of women who had
      access to a primary care provider, it was more common for the primary care
      provider to be aware of the pregnancy among LPs than among EPs (80.6% vs. 63.1%;
      P = 0.015). CONCLUSION: Some women delay presenting for abortion because of
      discouragement from friends and family. It is unclear whether there are
      educational or policy interventions that can have an impact on this delay, and
      this warrants further study. There may be ways of addressing the delay in
      referral by primary care providers. Further study into the causes for delay in
      referral for abortion is warranted.

PMID- 25764036
TI  - Myomectomy to conserve fertility: seven-year follow-up.
AB  - OBJECTIVE: To observe the occurrence of pregnancy in women undergoing minimally
      invasive and open myomectomy for symptoms attributed to uterine fibroids and who
      desire future pregnancy. METHODS: We performed a retrospective chart review of
      women who had undergone myomectomy at least two years previously within the Henry
      Ford Health System in Detroit, MI. We reviewed the subsequent fertility outcomes
      according to the fertility goals identified by each woman. RESULTS: During the
      seven-year observation window, 310 women underwent myomectomy and 124 (40%) of
      these women desired pregnancy. Forty-nine women desiring pregnancy (40%)
      conceived, and 30 (61% of those who conceived) delivered a viable infant from
      their first pregnancy. In addition, two women had a live birth after a
      miscarriage, and one had a live birth after an ectopic pregnancy. Five women had
      a second live-born baby. There were no differences in the occurrence of pregnancy
      or pregnancy outcome according to surgical approach, patient age or race, number
      of uterine incisions, or whether the endometrial cavity was entered. In addition,
      five of 186 women who did not have a fertility goal (3%) conceived, and one woman
      delivered two babies. CONCLUSION: Myomectomy performed to preserve fertility
      resulted in approximately one in four women having a live birth, independent of
      surgical technique.

PMID- 25764037
TI  - Ureteric injury during transvaginal ultrasound guided oocyte retrieval.
AB  - BACKGROUND: Transvaginal ultrasound guided oocyte retrieval during in vitro
      fertilization is performed routinely around the world and has reduced the
      occurrence of intra-abdominal injury considerably over laparoscopic procedures.
      Despite this, injuries do occur. CASE: We report a case of a 37-year-old patient
      who underwent IVF and encountered a ureteric injury during oocyte retrieval,
      which was recognized early and treated with ureteral stents with full resolution.
      During a subsequent IVF cycle, stenting of the ureters allowed better
      visualization, resulting in an uneventful retrieval and subsequent pregnancy.
      CONCLUSION: Ureteric injury can occur during transvaginal ultrasound guided egg
      retrieval. Prompt recognition is vital to successful treatment. Stenting of the
      ureters is the most common therapeutic modality and can be used in subsequent
      retrievals to identify the ureters.

PMID- 25764038
TI  - The use of antidepressants in pregnancy: focus on maternal risks.
AB  - Studies have consistently reported a decrease in the use of antidepressants
      during pregnancy compared with the pre-pregnancy period. Multiple recent studies
      have focused on the potential fetal risks of selective serotonin reuptake
      inhibitors (SSRIs) and selective norepinephrine reuptake inhibitors (SNRIs), with
      very little attention paid to maternal risks. The maternal risks of these
      medications are the focus of this review. Untreated depression is associated with
      increased risks of maternal morbidity, both somatic and psychiatric. In contrast,
      use of antidepressants has been associated with increased risks of hypertension,
      preeclampsia, and bleeding. In this review we present the evidence for maternal
      risks in an attempt to develop a risk-benefit ratio. 

PMID- 25764039
TI  - Left out in the cold: arguments against non-medical oocyte cryopreservation.

PMID- 25764041
TI  - Copper-catalyzed radical reaction of N-tosylhydrazones: stereoselective synthesis
      of (E)-vinyl sulfones.
AB  - A new chemistry of hydrazines that is a copper-catalyzed radical reaction to
      synthesize vinyl sulfones from readily available N-tosylhydrazones has been
      described. The protocol provides a novel strategy for the synthesis of various
      vinyl sulfones including alpha, beta-disubstituted ones and terminal ones. The
      advantages of the transformation include excellent E stereoselectivity, broad
      substrate scope, low cost of reagents, and convenient operation. A novel and
      efficient one-pot synthesis of alkynes from N-tosylhydrazones has been achieved.
      The studies provide important complementary approaches for the syntheses of vinyl
      sulfones and alkynes. 

PMID- 25764040
TI  - Technical update on tissue morcellation during gynaecologic surgery: its uses,
      complications, and risks of unsuspected malignancy.
AB  - OBJECTIVE: To review the use of tissue morcellation in minimally invasive
      gynaecological surgery. OUTCOMES: Morcellation may be used in gynaecological
      surgery to allow removal of large uterine specimens, providing women with a
      minimally invasive surgical option. Adverse oncologic outcomes of tissue
      morcellation should be mitigated through improved patient selection, preoperative
      investigations, and novel techniques that minimize tissue dispersion. EVIDENCE:
      Published literature was retrieved through searches of PubMed and Medline in the
      spring of 2014 using appropriate controlled vocabulary (leiomyomsarcoma, uterine
      neoplasm, uterine myomectomy, hysterectomy) and key words (leiomyoma, endometrial
      cancer, uterine sarcoma, leiomyosarcoma, morcellation, and MRI). Results were
      restricted to systematic reviews, randomized control trials/controlled clinical
      trials, and observational studies. There were no date limits but results were
      limited to English or French language materials. Searches were updated on a
      regular basis and incorporated in the guideline to August 2014. Grey
      (unpublished) literature was identified through searching the websites of health
      technology assessment and health technology assessment-related agencies, clinical
      practice guideline collections, clinical trial registries, and national and
      international medical specialty societies. VALUES: The quality of evidence in
      this document was rated using the criteria described in the report of the
      Canadian Task Force on Preventive Health Care. (Table 1) BENEFITS, HARMS, AND
      COSTS: Gynaecologists may offer women minimally invasive surgery and this may
      involve tissue morcellation and the use of a power morcellator for specimen
      retrieval. Women should be counselled that in the case of unexpected uterine
      sarcoma or endometrial cancer, the use of a morcellator is associated with
      increased risk of tumour dissemination. Appropriate training and safe practices
      should be in place before offering tissue morcellation. SUMMARY STATEMENTS: 1.
      Uterine sarcomas may be difficult to diagnose preoperatively. The risk of an
      unexpected uterine sarcoma following surgery for presumed benign uterine
      leiomyoma is approximately 1 in 350, and the rate of leiomyosarcoma is 1 in 500.
      (II-2) This risk increases with age. (II-2) 2. An unexpected uterine sarcoma
      treated by primary surgery involving tumour disruption, including morcellation of
      the tumour, has the potential for intra-abdominal tumour-spread and a worse
      prognosis. (II-2) 3. Uterus-sparing surgery remains a safe option for patients
      with symptomatic leiomyomas who desire future fertility. (II-1) RECOMMENDATIONS:
      1. Techniques for morcellation of a uterine specimen vary, and physicians should
      consider employing techniques that minimize specimen disruption and intra
      abdominal spread. (III-C) 2. Each patient presenting with uterine leiomyoma
      should be assessed for the possible presence of malignancy, based on her risk
      factors and preoperative imaging, although the value of these is limited. (III-C)
      3. Preoperative endometrial biopsy and cervical assessment to avoid morcellation
      of potentially detectable malignant and premalignant conditions is recommended.
      (II-2A) 4. Hereditary cancer syndromes that increase the risk of uterine
      malignancy should be considered a contraindication to uncontained uterine
      morcellation. (III-C) 5. Uterine morcellation is contraindicated in women with
      established or suspected cancer. (II-2A) If there is a high index of suspicion of
      a uterine sarcoma prior to surgery, patients should be advised to proceed with a
      total abdominal hysterectomy, bilateral salpingectomy, and possible oophorectomy.
      (II-2C) A gynaecologic oncology consultation should be obtained. 6. Tissue
      morcellation techniques require appropriate training and experience. Safe
      practice initiatives surrounding morcellation technique and the use of equipment
      should be implemented at the local level. (II-3B) 7. Morcellation is an
      acceptable option for retrieval of benign uterine specimens and may facilitate a
      minimally invasive surgical approach, which is associated with decreased
      perioperative risks. Each patient should be counselled about the possible risks
      associated with the use of morcellation, including the risks associated with
      underlying malignancy. (III-C).

PMID- 25764042
TI  - Effect of Base and Inlay Restorative Material on the Stress Distribution and
      Fracture Resistance of Weakened Premolars.
AB  - The purpose of this study was to evaluate the influence of direct base and
      indirect inlay materials on stress distribution and fracture resistance of
      endodontically treated premolars with weakened cusps. Forty healthy human
      premolars were selected; five were left intact as controls (group C+), and the
      others were subjected to endodontic treatment and removal of buccal and lingual
      cusp dentin. Five teeth were left as negative controls (group C-). The remaining
      30 teeth were divided into two groups according to the direct base material
      (glass ionomer [GIC] or composite resin [CR]). After base placement, each group
      was subjected to extensive inlay preparation, and then three subgroups were
      created (n=5): no inlay restoration (GIC and CR), restored with an indirect
      composite resin inlay (GIC+IR and CR+IR), and restored with a ceramic inlay
      (GIC+C and CR+C). Each specimen was loaded until fracture in a universal testing
      machine. For finite element analysis, the results showed that the removal of
      tooth structure significantly affected fracture resistance. The lowest values
      were presented by the negative control group, followed by the restored and based
      groups (not statistically different from each other) and all lower than the
      positive control group. In finite element analysis, the stress concentration was
      lower in the restored tooth compared to the tooth without restoration, whereas in
      the restored teeth, the stress concentration was similar, regardless of the
      material used for the base or restoration. It can be concluded that the inlay
      materials combined with a base showed similar behavior and were not able to
      regain the strength of intact tooth structure. 

PMID- 25764043
TI  - The Effect of Hydrofluoric Acid Concentration on the Bond Strength and Morphology
      of the Surface and Interface of Glass Ceramics to a Resin Cement.
AB  - The purpose of this study was to evaluate the influence of various concentrations
      of hydrofluoric acid (HF) on the surface/interface morphology and MU-shear bond
      strength (MUSBS) between IPS Empress Esthetic (EST) (Ivoclar Vivadent) and IPS
      e.max Press (EMX) (Ivoclar Vivadent) ceramics and resin cement. Ceramic blocks
      were divided into 12 groups for each kind of ceramic. Six different HF
      concentrations were evaluated: 1%, 2.5%, 5%, 7.5%, 10%, and 15%. All groups were
      silanated after etching, and half of the specimens within each group received a
      thin layer of unfilled resin (UR). Three resin cement cylinders were prepared on
      each ceramic block for MUSBS testing. The specimens were stored in distilled
      water at 37 degrees C for 24 hours. The MUSBS test was carried out in a universal
      testing machine at a crosshead speed of 0.5 mm/min until fracture. The data were
      submitted to three-way analysis of variance and multiple comparisons were
      performed using the Tukey post hoc test (p<0.05). The etched surfaces and bonded
      interfaces were evaluated using scanning electron microscopy. MUSBS means (MPa)
      for 1%, 2.5%, 5%, 7.5%, 10%, and 15% HF concentrations were, respectively, 25.2,
      27.2, 30.1, 31.4, 33.3, and 31.8. MUSBS means with or without UR application
      measured 32.24 and 27.4, respectively; EST and EMX measured 29.8 and 29.9,
      respectively. For the HF concentrations, 10% and 15% showed higher MUSBS means
      than did 1% and 2.5% (p<0.05); 7.5% was higher than 1% (p<0.05); and no
      statistical differences were found among the other concentrations (p>0.05). When
      evaluating UR, MUSBS mean was significantly higher and better infiltration was
      observed on the etched surfaces. No statistical difference was found between the
      ceramics. The HF concentration and UR influenced the bond strength and
      surface/interface morphology. 

PMID- 25764045
TI  - Retention of Root Canal Posts: Effect of Cement Film Thickness, Luting Cement,
      and Post Pretreatment.
AB  - The aim of this study was to investigate the effect of the cement film thickness
      of a zinc phosphate or a resin cement on retention of untreated and pretreated
      root canal posts. Prefabricated zirconia posts (CosmoPost: 1.4 mm) and two types
      of luting cements (a zinc phosphate cement [DeTrey Zinc] and a self-etch adhesive
      resin cement [Panavia F2.0]) were used. After removal of the crowns of 360
      extracted premolars, canines, or incisors, the root canals were prepared with a
      parallel-sided drill system to three different final diameters. Half the posts
      did not receive any pretreatment. The other half received tribochemical silicate
      coating according to the manufacturer's instructions. Posts were then luted in
      the prepared root canals (n=30 per group). Following water storage at 37 degrees
      C for seven days, retention of the posts was determined by the pull-out method.
      Irrespective of the luting cement, pretreatment with tribochemical silicate
      coating significantly increased retention of the posts. Increased cement film
      thickness resulted in decreased retention of untreated posts and of pretreated
      posts luted with zinc phosphate cement. Increased cement film thickness had no
      influence on retention of pretreated posts luted with resin cement. Thus,
      retention of the posts was influenced by the type of luting cement, by the cement
      film thickness, and by the post pretreatment. 

PMID- 25764044
TI  - Increased Durability of Resin-Dentin Bonds Following Cross-Linking Treatment.
AB  - OBJECTIVES: This study evaluated the long-term effect of carbodiimide treatments
      of acid-etched dentin on resin-dentin bond strength of a simplified etch-and
      rinse adhesive system. METHODS: Forty-eight sound third molars were divided into
      three groups (n=16) according to the dentin treatment: G1: deionized water; G2:
      0.5 mol/L 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC) applied for 30
      seconds; and G3: 0.5 mol/L EDC applied for 60 seconds. Flat dentin surfaces were
      produced, etched with 37% phosphoric acid for 15 seconds, and then treated with
      deionized water for 60 seconds or with 0.5 mol/L EDC for 30 or 60 seconds prior
      to the application of Single Bond 2. Crowns were restored with resin composite,
      and beam specimens were prepared for microtensile testing. The beams from each
      group were tested 24 hours or 6 or 12 months after the adhesive procedures. One
      slab from each tooth was prepared and analyzed for nanoleakage. Bond strength
      (MPa) data were submitted to analysis of variance and Tukey test (alpha=0.05).
      RESULTS: The treatment of dentin with 0.5 mol/L EDC for 30 seconds (24.1+/-6.2
      MPa) and 60 seconds (25.5+/-5.1 MPa) did not negatively affect the immediate bond
      strength of Single Bond 2 when compared to the control group (24.6+/-7.3 MPa).
      Additionally, EDC prevented resin-dentin bond degradation after 12 months in
      artificial saliva for both periods of treatment. An increased accumulation of
      silver ions was seen for the control group over time, while a much lower amount
      of silver grains was observed for the EDC-treated groups. CONCLUSIONS: 0.5 mol/L
      EDC was able to prevent resin-dentin bond degradation after 12 months, especially
      when applied for 60 seconds.

PMID- 25764046
TI  - Principles of cerebral hemodynamics when intracranial pressure is raised: lessons
      from the peripheral circulation.
AB  - BACKGROUND: The brain is highly vascular and richly perfused, and dependent on
      continuous flow for normal function. Although confined within the skull, pressure
      within the brain is usually less than 15 mmHg, and shows small pulsations related
      to arterial pulse under normal circumstances. Pulsatile arterial hemodynamics in
      the brain have been studied before, but are still inadequately understood,
      especially during changes of intracranial pressure (ICP) after head injury.
      METHOD: In seeking cohesive explanations, we measured ICP and radial artery
      pressure (RAP) invasively with high-fidelity manometer systems, together with
      middle cerebral artery flow velocity (MCAFV) (transcranial Doppler) and central
      aortic pressure (CAP) generated from RAP, using a generalized transfer function
      technique, in eight young unconscious, ventilated adults following closed head
      trauma. We focused on vascular effects of spontaneous rises of ICP ('plateau
      waves'). RESULTS: A rise in mean ICP from 29 to 53 mmHg caused no consistent
      change in pressure outside the cranium, or in heart rate, but ICP pulsations
      increased in amplitude from 8 to 20 mmHg, and ICP waveform came to resemble that
      in the aorta. Cerebral perfusion pressure (=central aortic pressure - ICP), which
      equates with transmural pressure, fell from 61 to 36 mmHg. Mean MCAFV fell from
      53 to 40 cm/s, whereas pulsatile MCAFV increased from 77 to 98 cm/s. These
      significant changes (all P < 0.01) may be explained using the Monro-Kellie
      doctrine, because of compression of the brain, as occurs in a limb when external
      pressure is applied. CONCLUSION: The findings emphasize importance of reducing
      ICP, when raised, and on the additional benefits of reducing wave reflection from
      the lower body.

PMID- 25764047
TI  - The effect of losartan on differential reflex control of sympathetic nerve
      activity in chronic kidney disease.
AB  - BACKGROUND: The effect of angiotensin II type I receptor (AT1R) inhibition on the
      pattern of reflex sympathetic nerve activity (SNA) to multiple target organs in
      the Lewis polycystic kidney (LPK) rat model of chronic kidney disease was
      determined. METHODS: Mean arterial pressure (MAP), splanchnic SNA (sSNA), renal
      SNA (rSNA) and lumbar SNA (lSNA) were recorded in urethane-anaesthetized LPK and
      Lewis controls (total n = 39). Baroreflex, peripheral and central chemoreflex,
      and somatosensory reflex control of SNA (evoked by phenylephrine/sodium
      nitroprusside infusion, 10% O2 in N2 or 100% N2 ventilation, 5% CO2 ventilation
      and sciatic nerve stimulation, respectively) were determined before and after
      administration of losartan (AT1R antagonist 3 mg/kg, intravenous). RESULTS:
      Baseline MAP was higher in LPK rats and baroreflex control of sSNA and rSNA, but
      not lSNA, was reduced. Losartan reduced MAP in both strains and selectively
      improved baroreflex gain for sSNA (-1.2 +/- 0.1 vs. -0.7 +/- 0.07 %/mmHg; P <
      0.05) in LPK. The peripheral and central chemoreflex increased MAP and all SNA in
      Lewis controls, but reduced or had no effect on these parameters, respectively,
      in LPK. The SNA response to somatosensory stimulation was biphasic, with latency
      to second peak less in LPK. Losartan ameliorated the depressor and
      sympathoinhibitory responses to peripheral chemoreflex stimulation in the LPK,
      but did not alter the central chemoreflex or somatosympathetic responses.
      CONCLUSION: Inhibition of the AT1R selectively improved baroreflex control of
      sSNA and peripheral chemoreflex control of all three sympathetic nerve outflows
      in the LPK rat, suggesting these anomalies in reflex function are driven in part
      by angiotensin II.

PMID- 25764049
TI  - ECG left ventricular hypertrophy is a stronger risk factor for incident
      cardiovascular events in women than in men in the general population.
AB  - OBJECTIVE: Left ventricular hypertrophy (LVH) is a strong risk factor for
      cardiovascular events. ECG is the most widely used method for LVH detection.
      Despite the abundance of ECG LVH criteria, their prognostic values have been
      compared in only a few studies, and little has been known about how sex modifies
      the prognostic value of LVH. We assessed the relationship between ECG LVH and
      incident cardiovascular events in the general population. METHODS: Several ECG
      LVH criteria were measured in 3059 women and 2456 men participating in the Health
      2000 Study - a national general population survey. Association between ECG LVH
      and cardiovascular events were analyzed with Cox proportional-hazards models.
      RESULTS: ECG LVH was more prevalent in women than in men when measured with
      Cornell-based criteria, but less prevalent or nondifferent when measured with
      other criteria. The association between ECG LVH and events showed higher hazard
      ratios for women than in men. Sex * LVH interaction terms were statistically
      significant in part of the LVH criteria. In adjusted Cox models, Sokolow-Lyon
      voltage performed the best. The composite of Sokolow-Lyon voltage and Cornell
      voltage was statistically significantly associated with events in both sexes.
      CONCLUSION: Sex affects both the prevalence rates and prognostic values of ECG
      LVH criteria in the general population, while showing higher prognostic value of
      ECG LVH in women than in men. For clinical use, the composite of the Sokolow-Lyon
      voltage and the Cornell voltage seems to be a good option.

PMID- 25764050
TI  - Therapeutic Potential of Ocimum tenuiflorum as MPO Inhibitor with Implications
      for Atherosclerosis Prevention.
AB  - Current experimental studies show that Ocimum tenuiflorum (commonly known as
      basil or Tulsi) possesses many health benefits. Ocimum is suggested to be
      antioxidative and anti-inflammatory. Eugenol, an orthomethoxyphenol, and ursolic
      acid have been identified as important components of basil. Myeloperoxidase
      (MPO), an oxidative enzyme, has been implicated in the pathogenesis of
      atherosclerosis. MPO-dependent oxidation of lipoproteins has been implicated in
      foam cell formation, dysfunctional HDL, and abnormalities in reverse cholesterol
      transport. Whole leaf extract of O. tenuiflorum and its major components, eugenol
      and ursolic acid, inhibit the oxidation of lipoproteins by myeloperoxidase/copper
      as measured by conjugated diene formation as well as by the thiobarbituric acid
      reactive substance (TBARS) assay. Whole basil leaf extract is able to attenuate
      the lipopolysaccharide-induced inflammation in RAW 264.7 cells compared with its
      components. In addition, whole basil leaf extract and eugenol inhibited MPO
      enzyme activity against synthetic substrates. Based on these results, we conclude
      that basil extract could act as an inhibitor of MPO and may serve as a
      nonpharmacological therapeutic agent for atherosclerosis. 

PMID- 25764051
TI  - Self-Harm in Adolescents: A Self-Report Survey in Schools from Lisbon, Portugal.
AB  - The study aims to determine the prevalence of self-harm (SH) and related
      psychosocial factors in a large sample of Portuguese adolescents. A total of
      1,713 pupils, aged 12 to 20 years, completed an anonymous questionnaire in a
      school setting. In all, 7.3% reported at least 1 episode of SH: rates were 3
      times higher for females than males. Almost half reported repeated SH, most
      commonly self-cutting. Anxiety, depression, and substance abuse were linked to
      SH, and particularly repeated SH. Anxiety, trouble with the police, and exposure
      to SH or suicide of others, were independently associated with SH in both
      genders. These findings indicate that SH is a public health concern in Portugal
      as in other European countries.

PMID- 25764052
TI  - Venous thromboembolism in patients with liver diseases.

PMID- 25764053
TI  - Theme-based teaching of point-of-care ultrasound in undergraduate medical
      education.
AB  - A handful of medical schools have developed formal curricula to teach medical
      students point-of-care ultrasound; however, no ideal method has been proposed.
      The purpose of this study was to assess an innovative theme-based ultrasound
      educational model for undergraduate medical education. This was a single-center
      cross-sectional study conducted at an academic medical center. The study
      participants were 95 medical students with minimal or no ultrasound experience
      during their third year of training. The educational theme for the ultrasound
      session was "The evaluation of patients involved in motor vehicle collisions."
      This educational theme was carried out during all components of the 1-day event
      called SonoCamp: asynchronous learning, the didactic lecture, the skills
      stations, the team case challenge and the individual challenge stations.
      Assessment consisted of a questionnaire, team case challenge, and individual
      challenges. A total of 89 of 95 (94 %) students who participated in SonoCamp
      responded, and 92 % (87 of 95) completed the entire questionnaire before and
      after the completion of SonoCamp. Ninety-nine percent (95 % CI, 97-100 %) agreed
      that training at skill stations helped solidify understanding of point-of-care
      ultrasound. Ninety-two percent (95 % CI, 86-98 %) agreed that theme-based
      learning is an engaging learning style for point-of-care ultrasound. All students
      agreed that having a team exercise is an engaging way to learn point-of-care
      ultrasound; and of the 16 groups, the average score on the case-based questions
      was 82 % (SD + 28). The 1-day, theme-based ultrasound educational event was an
      engaging learning technique at our institution which lacks undergraduate medical
      education ultrasound curriculum.

PMID- 25764054
TI  - Relative contributions of Dehalobacter and zerovalent iron in the degradation of
      chlorinated methanes.
AB  - The role of bacteria and zerovalent iron (Fe(0)) in the degradation of
      chlorinated solvents in subsurface environments is of interest to researchers and
      remediation practitioners alike. Fe(0) used in reactive iron barriers for
      groundwater remediation positively interacted with enrichment cultures containing
      Dehalobacter strains in the transformation of halogenated methanes. Chloroform
      transformation and dichloromethane formation was up to 8-fold faster and 14 times
      higher, respectively, when a Dehalobacter-containing enrichment culture was
      combined with Fe(0) compared with Fe(0) alone. The dichloromethane-fermenting
      culture transformed dichloromethane up to three times faster with Fe(0) compared
      to without. Compound-specific isotope analysis was employed to compare abiotic
      and biotic chloroform and dichloromethane degradation. The isotope enrichment
      factor for the abiotic chloroform/Fe(0) reaction was large at -29.4 +/- 2.10/00,
      while that for chloroform respiration by Dehalobacter was minimal at -4.3 +/-
      0.450/00. The combined abiotic/biotic dechlorination was -8.3 +/- 0.70/00,
      confirming the predominance of biotic dechlorination. The enrichment factor for
      dichloromethane fermentation was -15.5 +/- 1.50/00; however, in the presence of
      Fe(0) the factor increased to -23.5 +/- 2.10/00, suggesting multiple mechanisms
      were contributing to dichloromethane degradation. Together the results show that
      chlorinated methane-metabolizing organisms introduced into reactive iron barriers
      can have a significant impact on trichloromethane and dichloromethane degradation
      and that compound-specific isotope analysis can be employed to distinguish
      between the biotic and abiotic reactions involved. 

PMID- 25764055
TI  - Autosomal Dominant Microcephaly Associated With Congenital Lymphedema and
      Chorioretinopathy Due to a Novel Mutation in KIF11.

PMID- 25764056
TI  - Long-Term Outcomes following the MEND 7-13 Child Weight Management Program.
AB  - BACKGROUND: In the current study, we report outcomes 2.4 years from baseline in a
      random subsample of overweight and obese children who attended MEND 7-13 programs
      delivered in UK community settings under service level conditions. METHODS: The
      study employed an uncontrolled pre-follow-up design. A total of 165 children were
      measured. Outcomes included anthropometry, parental perception of emotional
      distress, body esteem, and self-esteem. RESULTS: Overall, there were significant
      improvements in all outcomes apart from BMI z-score. In boys, BMI z-score, waist
      circumference z-score, and psychometrics all improved. In girls, there were no
      statistically significant differences at 2.4 years, except for body esteem.
      CONCLUSIONS: In real-world settings, the MEND intervention, when delivered by
      nonspecialists, may result in modest, yet positive, long-term outcomes.
      Subsequent research should focus on improving the outcome effect size, providing
      effective behavior change maintenance strategies, and further investigating the
      reasons behind the observed gender differences.

PMID- 25764058
TI  - Optimized arrangement of constant ambient air monitoring stations in the Kanto
      region of Japan.
AB  - Continuous ambient air monitoring systems have been introduced worldwide.
      However, such monitoring forces autonomous communities to bear a significant
      financial burden. Thus, it is important to identify pollutant-monitoring stations
      that are less efficient, while minimizing loss of data quality and mitigating
      effects on the determination of spatiotemporal trends of pollutants. This study
      describes a procedure for optimizing a constant ambient air monitoring system in
      the Kanto region of Japan. Constant ambient air monitoring stations in the area
      were topologically classified into four groups by cluster analysis and principle
      component analysis. Then, air pollution characteristics in each area were
      reviewed using concentration contour maps and average pollution concentrations.
      We then introduced three simple criteria to reduce the number of monitoring
      stations: (1) retain the monitoring station if there were similarities between
      its data and average data of the group to which it belongs; (2) retain the
      station if its data showed higher concentrations; and (3) retain the station if
      the monitored concentration levels had an increasing trend. With this procedure,
      the total number of air monitoring stations in suburban and urban areas was
      reduced by 36.5%. The introduction of three new types of monitoring stations is
      proposed, namely, mobile, for local non-methane hydrocarbon pollution, and Ox
      prioritized. 

PMID- 25764057
TI  - Association of light exposure on physical activity and sedentary time in young
      people.
AB  - BACKGROUND: To investigate whether light exposure was associated with objectively
      measured physical activity (PA) and sedentary behaviour in young people. METHODS:
      Participants (n=229, 46.7% female) were young people (mean 8.8 years [SD+/-2.2])
      from the borough of Camden, UK. Daily sedentary time, moderate and vigorous PA
      (MVPA) and light exposure were measured using a tri-axial accelerometer with an
      ambient light sensor during the summer. Multiple linear regression models
      examined associations between average daily light exposure, sedentary time and
      time in MVPA. Models were repeated investigating weekdays and weekend days
      separately. Analyses were adjusted for pre-specified covariables, including age,
      sex, device wear time, ethnic group, school and body fat. RESULTS: There were
      significant associations between average daily light exposure and time sedentary
      (beta coefficient=-11.2, 95% CI, -19.0 to -3.4) and in MVPA (beta
      coefficient=3.5, 95% CI, 1.2 to 5.9). Light exposure was significantly associated
      with weekend sedentary time (beta coefficient=-10.0, 95% CI, -17.6, -2.4),
      weekend MVPA (beta coefficient=3.7, 95% CI, 1.7, 5.7), weekday sedentary time
      (beta coefficient=-15.0, 95% CI, -22.7 to -7.2), but not weekday MVPA (beta
      coefficient=2.0, 95% CI, -0.5 to 4.5). CONCLUSION: Average daily light exposure
      is positively associated with time in MVPA and negatively associated with
      sedentary time. Increasing daylight exposure may be a useful intervention
      strategy for promoting physical activity.

PMID- 25764059
TI  - Health risk assessment related to waterborne pathogens from the river to the tap.
AB  - A two-year monitoring program of Cryptosporidium parvum oocysts, Giardia
      duodenalis cysts, Escherichia coli, Clostridium perfringens spores and adenovirus
      was conducted in three large rivers in France used for recreational activities
      and as a resource for drinking water production. Fifty-liter river water and one
      thousand-liter tap water samples were concentrated using hollow-fiber
      ultrafiltration and analyzed by molecular biology or laser-scanning cytometry. In
      order to evaluate watershed land use influence on microorganism concentration
      changes, occurrence and seasonality of microorganisms were studied. The highest
      concentrations of protozoan parasites and C. perfringens were found for one of
      the three sites, showing a high proportion of agricultural territories, forests
      and semi-natural environments, which may be partly attributable to soil leaching
      due to rainfall events. On the contrary, the highest concentrations of
      adenoviruses were found at the two other sites, probably due to strong urban
      activities. Health risk assessment was evaluated for each waterborne pathogen
      regarding exposure during recreational activities (for a single or five bathing
      events during the summer). The calculated risk was lower than 0.5% for parasites
      and varied from 1% to 42% for adenovirus. A theoretical assessment of
      microorganism removal during the drinking water treatment process was also
      performed, and it showed that an absence of microorganisms could be expected in
      finished drinking water. This hypothesis was confirmed since all tested tap water
      samples were negative for each studied microorganism, resulting in a risk for
      drinking water consumption lower than 0.01% for parasites and lower than 0.5% for
      adenovirus. 

PMID- 25764061
TI  - Anomalous self-diffusion and sticky Rouse dynamics in associative protein
      hydrogels.
AB  - Natural and synthetic materials based on associating polymers possess diverse
      mechanical behavior, transport properties and responsiveness to external stimuli.
      Although much is known about their dynamics on the molecular and macroscopic
      level, knowledge of self-diffusive dynamics of the network-forming constituents
      remains limited. Using forced Rayleigh scattering, anomalous self-diffusion is
      observed in model associating protein hydrogels originating from the
      interconversion between species that diffuse in both the molecular and associated
      state. The diffusion can be quantitatively modeled using a two-state model for
      polymers in the gel, where diffusivity in the associated state is critical to the
      super diffusive behavior. The dissociation time from bulk rheology measurements
      was 2-3 orders of magnitude smaller than the one measured by diffusion, because
      the former characterizes submolecular dissociation dynamics, whereas the latter
      depicts single protein molecules completely disengaging from the network.
      Rheological data also show a sticky Rouse-like relaxation at long times due to
      collective relaxation of large groups of proteins, suggesting mobility of
      associated molecules. This study experimentally demonstrates a hierarchy of
      relaxation processes in associating polymer networks, and it is anticipated that
      the results can be generalized to other associative systems to better understand
      the relationship of dynamics among sticky bonds, single molecules, and the entire
      network. 

PMID- 25764060
TI  - The mediating role of psychological capital on the association between
      occupational stress and job burnout among bank employees in China.
AB  - Although job burnout is common among bank employees, few studies have explored
      positive resources for combating burnout in this population. This study aims to
      explore the relationship between occupational stress and job burnout among
      Chinese bank employees, and particularly the mediating role of psychological
      capital. A cross-sectional study was conducted in Liaoning, China, during June to
      August of 2013. A questionnaire that included the effort-reward imbalance scale,
      the Psychological Capital Questionnaire and the Maslach Burnout Inventory-General
      Survey, as well as demographic and working factors, was distributed to 1739
      employees of state-owned banks. This yielded 1239 effective respondents (467 men,
      772 women). Asymptotic and resampling strategies explored the mediating role of
      psychological capital in the relationship between occupational stress and job
      burnout. Both extrinsic effort and overcommitment were positively associated with
      emotional exhaustion and depersonalisation. Meanwhile, reward was negatively
      associated with emotional exhaustion and depersonalisation, but positively
      associated with personal accomplishment. There was a gender difference in the
      mediating role of Psychological capital on the occupational stress-job burnout.
      In male bank employees, Psychological capital mediated the relationships of
      extrinsic effort and reward with emotional exhaustion and depersonalization; in
      female bank employees, it partially mediated the relationships of extrinsic
      effort, reward and overcommitment with emotional exhaustion and
      depersonalisation, as well as the relationship between reward and personal
      accomplishment. Psychological capital was generally a mediator between
      occupational stress and job burnout among Chinese bank employees. Psychological
      capital may be a potential positive resource in reducing the negative effects of
      occupational stress on job burnout and relieving job burnout among bank
      employees, especially female bank employees. 

PMID- 25764062
TI  - Reacting cyclopropenones with arynes: access to spirocyclic xanthene-cyclopropene
      motifs.
AB  - A formal insertion of two aryne moieties into the carbon-oxygen double bond of
      cyclopropenone has been realized. Spirocyclic xanthene-cyclopropene scaffolds
      were obtained. Mechanistically, a sequence of a formal [2 + 2]-cycloaddition
      followed by electrocyclic ring opening and a terminating [4 + 2]-type
      cycloaddition is postulated. The use of an electron-rich aryne precursor led to
      ring cleavage of the cyclopropene to afford an unprecedented xanthylium salt. 

PMID- 25764064
TI  - Muscle fatigue induced by a soccer match-play simulation in amateur Black South
      African players.
AB  - The purpose of the current study was to investigate the effects of a soccer
      specific fatigue protocol on the temporal changes in torque producing abilities
      of the thigh within African soccer players. Twenty amateur Black South African
      soccer players performed the SAFT(90) soccer match-play simulation protocol,
      while isokinetic measurements were obtained pre-exercise (T0), after the 1st half
      (T45), after half time (T60) and after the 2nd half (T105). During SAFT(90)
      performance, significant overall concentric quadriceps peak torque changes were
      observed (1.05 rad . s(-1) = 16.6%, 3.14 rad . s(-1) = 9.5%). Eccentric hamstring
      peak torque also decreased significantly over time (1.05 rad . s(-1) = 17.4%,
      3.14 rad . s(-1) = 18.5%), with significant reductions occurring during both
      halves. The functional strength ratio (eccH:conQ) at 3.14 rad . s(-1) was
      observed to significantly decrease by 10.1% overall. The indicated time-dependent
      changes in Black South African players have implications for competitive
      performance and increased predisposition to hamstring muscle injuries. Because of
      muscle fatigue, the hamstrings may have insufficient eccentric strength during
      the late swing phase when sprinting, resulting in eccentric overload and damage
      to the muscle. The changes in strength found in the current study help explain
      the increased predisposition to hamstring strains during the latter stages of
      both halves of match-play as reported by epidemiological studies. 

PMID- 25764065
TI  - Renin-angiotensin system: an old player with novel functions in skeletal muscle.
AB  - Skeletal muscle is a tissue that shows the most plasticity in the body; it can
      change in response to physiological and pathological stimuli. Among the diseases
      that affect skeletal muscle are myopathy-associated fibrosis, insulin resistance,
      and muscle atrophy. A common factor in these pathologies is the participation of
      the renin-angiotensin system (RAS). This system can be functionally separated
      into the classical and nonclassical RAS axis. The main components of the
      classical RAS pathway are angiotensin-converting enzyme (ACE), angiotensin II
      (Ang-II), and Ang-II receptors (AT receptors), whereas the nonclassical axis is
      composed of ACE2, angiotensin 1-7 [Ang (1-7)], and the Mas receptor.
      Hyperactivity of the classical axis in skeletal muscle has been associated with
      insulin resistance, atrophy, and fibrosis. In contrast, current evidence supports
      the action of the nonclassical RAS as a counter-regulator axis of the classical
      RAS pathway in skeletal muscle. In this review, we describe the mechanisms
      involved in the pathological effects of the classical RAS, advances in the use of
      pharmacological molecules to inhibit this axis, and the beneficial effects of
      stimulation of the nonclassical RAS pathway on insulin resistance, atrophy, and
      fibrosis in skeletal muscle. 

PMID- 25764063
TI  - Neutrophils: Between host defence, immune modulation, and tissue injury.
AB  - Neutrophils, the most abundant human immune cells, are rapidly recruited to sites
      of infection, where they fulfill their life-saving antimicrobial functions. While
      traditionally regarded as short-lived phagocytes, recent findings on long-term
      survival, neutrophil extracellular trap (NET) formation, heterogeneity and
      plasticity, suppressive functions, and tissue injury have expanded our
      understanding of their diverse role in infection and inflammation. This review
      summarises our current understanding of neutrophils in host-pathogen interactions
      and disease involvement, illustrating the versatility and plasticity of the
      neutrophil, moving between host defence, immune modulation, and tissue damage. 

PMID- 25764066
TI  - Quantification of nanoparticle endocytosis based on double fluorescent pH
      sensitive nanoparticles.
AB  - Amorphous silica is a particularly interesting material because of its inertness
      and chemical stability. Silica nanoparticles have been recently developed for
      biomedical purposes but their innocuousness must be carefully investigated before
      clinical use. The relationship between nanoparticles physicochemical features,
      their uptake by cells and their biological activity represents a crucial issue,
      especially for the development of nanomedicine. This work aimed at adapting a
      method for the quantification of nanoparticle endocytosis based on pH-sensitive
      and double fluorescent particles. For that purpose, silica nanoparticles
      containing two fluorophores: FITC and pHrodo(TM) were developed, their respective
      fluorescence emission depends on the external pH. Indeed, FITC emits a green
      fluorescence at physiological pH and pHrodo(TM) emits a red fluorescence which
      intensity increased with acidification. Therefore, nanoparticles remained outside
      the cells could be clearly distinguished from nanoparticles uptaken by cells as
      these latter could be spotted inside cellular acidic compartments (such as
      phagolysosomes, micropinosomes...). Using this model, the endocytosis of 60 nm
      nanoparticles incubated with the RAW 264.7 macrophages was quantified using time
      lapse microscopy and compared to that of 130 nm submicronic particles. The amount
      of internalized particles was also evaluated by fluorimetry. The biological
      impact of the particles was also investigated in terms of cytotoxicity, pro
      inflammatory response and oxidative stress. Results clearly demonstrated that
      nanoparticles were more uptaken and more reactive than submicronic particles.
      Moreover, we validated a method of endocytosis quantification. 

PMID- 25764067
TI  - Complexation of bioreducible cationic polymers with gold nanoparticles for
      improving stability in serum and application on nonviral gene delivery.
AB  - Widespread applications of conventional polymeric gene carriers are greatly
      hampered by their inefficient transfection performance under serum-containing
      environment. Aiming to overcome this limitation, we propose a bioreducible
      polyethylenimine-gold nanocomplex system (SSPEI-Au NC), which can be prepared by
      a simple layer-by-layer (LBL) assembly procedure. SSPEI-Au NC contains
      sequentially deposited layers of bioreducible polyethylenimine (SSPEI) and
      poly(gamma-glutamic acid) (gamma-PGA) for efficient binding and delivery of
      plasmid DNA (pDNA). SSPEI-Au NC was characterized for various physicochemical
      properties, including: UV-vis spectra, TEM imaging, hydrodynamic size, and pDNA
      binding ability. The SSPEI-Au NC were efficiently uptaken by mammalian cells as
      observed using dark-field microscopy. Comparing to nondegradable PEI25k, the
      bioreducible SSPEI-Au NC exhibited superior transfection capability under serum
      containing condition while causing lower cytotoxicity on mammalian cell lines.
      The effect of serum on SSPEI-Au NC dispersity was studied using UV-vis
      spectrometry and the results suggest that serum-assisted colloidal stability of
      SSPEI-Au NC contributed to its serum-resistant transfection. 

PMID- 25764069
TI  - Characterization of phenolic compounds of thorny and thornless blackberries.
AB  - The aim of this study was to identify and compare the contents of phenolic acids,
      tannins, anthocyanins, and flavonoid glycosides in thorny and thornless
      blackberries. Five thorny and nine thornless cultivars were used for this study.
      Thirty-five phenolic compounds were determined in the examined fruits, and one
      phenolic acid, three ellagic acid derivatives, one anthocyanin, and six flavonols
      were characterized for the first time in blackberries. The thornless fruits were
      characterized by a higher content of anthocyanins (mean = 171.23 mg/100 g FW),
      ellagitannins (mean = 3.65 mg/100 g FW), and ellagic acid derivatives (mean =
      2.49 mg/100 g FW), in comparison to thorny ones. At the same time, in thorny
      fruits, the contents of hydroxycinnamic acids (mean = 1.42 mg/100 g FW) and
      flavonols (mean = 5.70 mg/100 g FW) were higher. 

PMID- 25764068
TI  - Neonatal infection with species C adenoviruses confirmed in viable cord blood
      lymphocytes.
AB  - Credible but conflicting reports address the frequency of prenatal infection by
      species C adenovirus. This question is important because these viruses persist in
      lymphoid cells and suppress double-stranded DNA-break repair. Consequently,
      prenatal adenovirus infections may generate the aberrant clones of lymphocytes
      that precede development of childhood acute lymphoblastic leukemia (ALL). The
      present study was designed to overcome technical limitations of prior work by
      processing cord blood lymphocytes within a day of collection, and by analyzing
      sufficient numbers of lymphocytes to detect adenovirus-containing cells at the
      lower limits determined by our previous studies of tonsil lymphocytes. By this
      approach, adenoviral DNA was identified in 19 of 517 (3.7%) samples, providing
      definitive evidence for the occurrence of prenatal infection with species C
      adenoviruses in a significant fraction of neonates predominantly of African
      American and Hispanic ancestry. Cord blood samples were also tested for the
      presence of the ETV6-RUNX1 translocation, the most common genetic abnormality in
      childhood ALL. Using a nested PCR assay, the ETV6-RUNX1 transcript was detected
      in four of 196 adenovirus-negative samples and one of 14 adenovirus-positive cord
      blood samples. These findings indicate that this method will be suitable for
      determining concordance between adenovirus infection and the leukemia-associated
      translocations in newborns. 

PMID- 25764070
TI  - 2015 AAHA/AAFP Pain Management Guidelines for Dogs and Cats.
AB  - The robust advances in pain management for companion animals underlie the
      decision of AAHA and AAFP to expand on the information provided in the 2007
      AAHA/AAFP Pain Management Guidelines for Dogs and Cats . The 2015 guidelines
      summarize and offer a discriminating review of much of this new knowledge. Pain
      management is central to veterinary practice, alleviating pain, improving patient
      outcomes, and enhancing both quality of life and the veterinarian-client-patient
      relationship. The management of pain requires a continuum of care that includes
      anticipation, early intervention, and evaluation of response on an individual
      patient basis. The guidelines include both pharmacologic and nonpharmacologic
      modalities to manage pain; they are evidence-based insofar as possible and
      otherwise represent a consensus of expert opinion. Behavioral changes are
      currently the principal indicator of pain and its course of improvement or
      progression, and the basis for recently validated pain scores. A team-oriented
      approach, including the owner, is essential for maximizing the recognition,
      prevention, and treatment of pain in animals. Postsurgical pain is eminently
      predictable but a strong body of evidence exists supporting strategies to
      mitigate adaptive as well as maladaptive forms. Degenerative joint disease is one
      of the most significant and under-diagnosed diseases of cats and dogs.
      Degenerative joint disease is ubiquitous, found in pets of all ages, and
      inevitably progresses over time; evidence-based strategies for management are
      established in dogs, and emerging in cats. These guidelines support veterinarians
      in incorporating pain management into practice, improving patient care. 

PMID- 25764071
TI  - Fluid replacement therapy for acute episodes of pain in people with sickle cell
      disease.
AB  - BACKGROUND: Treating vaso-occlusive painful crises in people with sickle cell
      disease is complex and requires multiple interventions. Extra fluids are
      routinely given as adjunct treatment, regardless of the individual's state of
      hydration with the aim of slowing or stopping the sickling process and thereby
      alleviating pain. This is an update of a previously published Cochrane Review.
      OBJECTIVES: To determine the optimal route, quantity and type of fluid
      replacement for people with sickle cell disease with acute painful crises. SEARCH
      METHODS: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group
      Trials Register which comprises of references identified from comprehensive
      electronic database searches and handsearches of relevant journals and abstract
      books of conference proceedings.We also conducted searches of Embase (November
      2007), LILACS and www.ClinicalTrials.gov (05 January 2010).Date of most recent
      search of the Group's Haemoglobinopathies Trials Register: 24 September 2014.
      SELECTION CRITERIA: Randomised and quasi-randomised controlled trials that
      compared the administration of supplemental fluids adjunctive to analgesics by
      any route in people with any type of sickle cell disease during an acute painful
      episode, under medical supervision (inpatient, day care or community). DATA
      COLLECTION AND ANALYSIS: No relevant trials have yet been identified. MAIN
      RESULTS: Sixteen trials were identified by the searches, all of which were not
      eligible for inclusion in the review. AUTHORS' CONCLUSIONS: Treating vaso
      occlusive crises is complex and requires multiple interventions. Extra fluids,
      generally oral or intravenous, are routinely administered during acute painful
      episodes to people with sickle cell disease regardless of the individual's state
      of hydration. Reports of their use during these acute painful episodes do not
      state the efficacy of any single route, type or quantity of fluid compared to
      another. However, there are no randomised controlled trials that have assessed
      the safety and efficacy of different routes, types or quantities of fluid. This
      systematic review identifies the need for a multicentre randomised controlled
      trial assessing the efficacy and possible adverse effects of different routes,
      types and quantities of fluid administered to people with sickle cell disease
      during acute painful episodes.

PMID- 25764072
TI  - Cycle of coercion: experiences of maltreatment and disciplinary measures in
      Canadian inmates.
AB  - PURPOSE: In spite of past and current efforts at implementing effective
      rehabilitative interventions in carceral settings, institutions of confinement
      are primarily concerned with the maintenance of order within their walls. The
      purpose of this paper is to better understand associations between inmates'
      developmental background and the experience of institutional discipline, to
      collect information on childhood maltreatment and disciplinary measures for a
      sample of Canadian prisoners. DESIGN/METHODOLOGY/APPROACH: Information relative
      to socio-economic background, childhood maltreatment and experience of discipline
      while in custody was obtained using face-to-face interviews and institutional
      file review for a sample of 416 male and 106 female offenders in Canadian
      provincial institutions. FINDINGS: Results from logistic regression analyses
      provided support for the association between childhood maltreatment and the
      experience of discipline, specifically in the form of increased monitoring from
      correctional staff. Furthermore, this association was found to be more pronounced
      for female offenders. RESEARCH LIMITATIONS/IMPLICATIONS: The findings highlight
      the need to incorporate a developmental perspective to current understanding of
      the use of disciplinary interventions in a prison environment. Such an approach
      may allow for preventing the enactment of a cycle of coercion, with negative
      consequences for the inmates. ORIGINALITY/VALUE: This study is original in its
      use of latent variable analytic methods to uncover the structure underlying the
      construct of childhood maltreatment in adult offenders. In addition, it provides
      valuable data of interest to researchers, corrections personnel and policy makers
      on the possible links between earlier developmental experiences and adjustment to
      the prison environment.

PMID- 25764073
TI  - Violence and the perceived risks of taking antiretroviral therapy in US jails and
      prisons.
AB  - PURPOSE: About one in five men living with HIV in the USA passes through a
      correctional center annually. Jails and prisons are seen therefore as key
      intervention sites to promote HIV treatment as prevention. Almost no research,
      however, has examined inmates' perspectives on HIV treatment or their strategies
      for retaining access to antiretroviral therapy (ART) during incarceration. The
      purpose of this paper is to describe the results of an exploratory study
      examining men's perceptions of and experiences with HIV care and ART during
      incarceration. DESIGN/METHODOLOGY/APPROACH: Semi-structured, in-depth interviews
      were conducted with 42 HIV positive male and male-to-female transgendered persons
      recently released from male correctional centers in Illinois, USA. FINDINGS:
      Interpersonal violence, a lack of safety, and perceived threats to privacy were
      frequently cited barriers to one's willingness and ability to access and adhere
      to treatment. Over 60 percent of study participants reported missed doses or
      sustained treatment interruption (greater than two weeks) because of failure to
      disclose their HIV status, delayed prescribing, intermittent dosing and out-of
      stock medications, confiscation of medications, and medication strikes. RESEARCH
      LIMITATIONS/IMPLICATIONS: Substantial improvements in ART access and adherence
      are likely to follow organizational changes that make incarcerated men feel
      safer, facilitate HIV status disclosure, and better protect the confidentiality
      of inmates receiving ART. ORIGINALITY/VALUE: This study identified novel causes
      of ART non-adherence among prisoners and provides first-hand information about
      how violence, stigma, and the pursuit of social support influence prisoner's
      decisions to disclose their HIV status or accept ART during incarceration.

PMID- 25764074
TI  - Detection of drugs in Australian prisons: supply reduction strategies.
AB  - PURPOSE: Prisoners have a high level of drug use prior to imprisonment. Many
      inmates report having injected drugs and using cannabis. Prison authorities
      employed a range of strategies to detect drugs and drug use in prison. However,
      it was unclear which supply reduction strategies operated, and the prevalence and
      types of drugs detected in Australian prisons. The purpose of this paper is to
      examine supply reduction strategies in Australian prisons. Information on
      searches for drugs, and from inmate urinalysis was collected. The study focussed
      on adults in fulltime custody in Australia in 2009. DESIGN/METHODOLOGY/APPROACH:
      A representative of all corrective services departments and justice health
      services was asked to complete a questionnaire on supply reduction strategies,
      including searches for drugs and drug testing of inmates. FINDINGS: The two main
      supply reduction strategies identified in all Australian prisons were the use of
      drug detection dogs and urinalysis programs. Despite an extensive use of drug
      searches and urinalysis, the detection of drugs was modest for both strategies.
      The most commonly used drug was cannabis with the detection of drugs such as
      amphetamines and heroin being very low. RESEARCH LIMITATIONS/IMPLICATIONS: Prison
      inmates have a history of high levels of drug use prior to imprisonment. However,
      the supply reduction measures of drug detection dogs and urinalysis indicate that
      drug use was low in Australian prisons. PRACTICAL IMPLICATIONS: The paper
      recommends that urinalysis comprises targeting testing regimes and that random
      testing ceases in order to be a more cost effective use of resources for drug
      detection. ORIGINALITY/VALUE: The study is the first report on the range of
      supply reduction measures in Australian prisons and, possibly in the world. Both
      measures were employed extensively across the country and finds of drugs and drug
      use were relatively low. Two possible conclusions can be drawn; that either drug
      use was very low in prison or that it was well concealed from the authorities. A
      comparison of random testing with targeted testing of inmates, where the former
      yields fewer positive results shows drug use was likely to be low rather than
      well concealed.

PMID- 25764075
TI  - Researching the psychological therapies in prison: considerations and future
      recommendations.
AB  - PURPOSE: The psychological therapies are widely considered within the forensic
      literature as holding a useful role in the prison system, however, despite this,
      very little research into the psychological therapies has taken place. Further,
      where research is carried out, it is often associated with the need for evidence
      based practice (EBP), involving quantification and randomization. The paper aims
      to discuss these issues. DESIGN/METHODOLOGY/APPROACH: This paper will initially
      introduce the importance of research into the psychological therapies in prison,
      followed by a consideration of EBP which can be thought of as the current
      movement governing research in the psychological therapies in the UK. FINDINGS:
      However, in providing a focused critique of EBP, particularly within prisons,
      this paper will attempt to pave the way for a consideration of alternative
      research methodologies and resultant methods in researching the psychological
      therapies in prisons in the UK. ORIGINALITY/VALUE: Through this it is argued that
      research within the prison setting should act not to promote interventions and
      create an evidence-based as such, but to provide an accessible body of knowledge
      for the psychological therapists working in prisons in the UK.

PMID- 25764076
TI  - Prevalence of psychiatric disorders among juvenile offenders in Malaysian prisons
      and association with socio-demographic and personal factors.
AB  - PURPOSE: The number of juvenile offenders admitted to Malaysian prisons is
      alarming. The purpose of this paper is to determine the presence of any
      psychiatric disorders and their association with personal characteristics of
      juvenile detainees in prisons across Peninsular Malaysia.
      DESIGN/METHODOLOGY/APPROACH: Detainees were recruited from five different prisons
      in Peninsular Malaysia and interviewed by a psychiatrist using the MINI-Kid and
      FACES-IV, relevant personal and family information was also collected. FINDINGS:
      A total of 105 detainees participated in the study. Almost all of the offenders
      (93.3 per cent) had at least one diagnosable psychiatric disorder and more than
      half (76.2 per cent) had two or more psychiatric diagnoses. Conduct disorder (CD)
      was the commonest disorder (59.0 per cent), while substance use disorders (SUD)
      was the commonest co-morbidity. A significant correlation was found between
      presence of CD, education level and SUD. Almost all (61/62, 98.4 per cent) of the
      detainees with CD, had not completed schooling (OR 8.03, 95 per cent CI 1.01
      71.35), and detainees with this disorder were more likely to use substances than
      detainees without CD (OR 4.35, 95 per cent CI 1.90-9.99). Detainees with any
      psychiatric diagnosis were more likely to have four or more siblings in their
      families (OR 5.5, 95 per cent CI 1.1-26.9). ORIGINALITY/VALUE: There is a high
      prevalence of psychiatric disorders among juvenile offenders in Malaysian
      prisons, detection and intervention would be important.

PMID- 25764077
TI  - Erratum to: Anosmin-1 over-expression regulates oligodendrocyte precursor cell
      proliferation, migration and myelin sheath thickness.

PMID- 25764079
TI  - Design and Synthesis of Mannich bases as Benzimidazole Derivatives as Analgesic
      Agents.
AB  - Mannich bases were selected for 2D QSAR study to derive meaningful relationship
      between the structural features and analgesic activity. Using the knowledge of
      important features a novel series was designed to obtain improved analgesic
      activity. A series of novel Mannich bases 1-(N-substituted amino)methyl]-2
      substituted benzimidazole derivatives were synthesized and were screened for
      analgesic activity. Some of these compounds showed promising analgesic activity
      when compared with the standard drug diclofenac sodium. 

PMID- 25764078
TI  - GSK3beta inhibition promotes synaptogenesis in Drosophila and mammalian neurons.
AB  - The PI3K-dependent activation of AKT results in the inhibition of GSK3beta in
      most signaling pathways. These kinases regulate multiple neuronal processes
      including the control of synapse number as shown for Drosophila and rodents.
      Alzheimer disease's patients exhibit high levels of circulating GSK3beta and,
      consequently, pharmacological strategies based on GSK3beta antagonists have been
      designed. The approach, however, has yielded inconclusive results so far. Here,
      we carried out a comparative study in Drosophila and rats addressing the role of
      GSK3beta in synaptogenesis. In flies, the genetic inhibition of the shaggy
      encoded GSK3beta increases the number of synapses, while its upregulation leads
      to synapse loss. Likewise, in three weeks cultured rat hippocampal neurons, the
      pharmacological inhibition of GSK3beta increases synapse density and Synapsin
      expression. However, experiments on younger cultures (12 days) yielded an
      opposite effect, a reduction of synapse density. This unexpected finding seems to
      unveil an age- and dosage-dependent differential response of mammalian neurons to
      the stimulation/inhibition of GSK3beta, a feature that must be considered in the
      context of human adult neurogenesis and pharmacological treatments for
      Alzheimer's disease based on GSK3beta antagonists. 

PMID- 25764080
TI  - Saturated Fat Controversy: Importance of Systematic Reviews and Meta-analyses.
AB  - In adults, worldwide, the number one cause of death is coronary heart disease.
      Current guidelines generally recommend reduced consumption of saturated fat to
      reduce the risk of cardiovascular disease. However, some evidence suggests that
      consumption of saturated fat does not increase that risk. Recently, to address
      the saturated fat controversy, i.e., whether or not saturated fat intake is a
      risk factor for cardiovascular disease, a number of systematic reviews and meta
      analyses were performed. This paper aims to provide tools for understanding both.
      It starts with an overview of the basic principles of systematic reviews and meta
      analyses. Then, it provides examples of current evidence from systematic reviews
      on the relationship between saturated fat intake and the risk of cardiovascular
      disease. Finally, based on an example from one recent systematic review, it
      explains how to read a meta-analysis. Continuous updating of existing reviews, as
      well as the development of new systematic reviews, is needed in areas in which
      the role of saturated fat remains unclear. 

PMID- 25764081
TI  - Successful self-management among non-insulin-treated adults with Type 2 diabetes:
      a self-regulation perspective.
AB  - AIMS: To clarify the role of self-monitoring of blood glucose (SMBG) in the self
      management of Type 2 diabetes from the patient's perspective, using in-depth
      interviews with non-insulin-treated adults to investigate how they learned to
      manage their diabetes effectively and whether SMBG played a significant role in
      this process. METHODS: Individual interviews were conducted with 14 non-insulin
      treated adults with Type 2 diabetes who had significantly improved their
      glycaemic control [64% women; 50% black; 21% Hispanic; mean age 60 years; mean
      HbA(1c) concentration 43 mmol/mol (6.1%)]. Interviews were transcribed and
      analysed by a coding team, applying the concept of illness coherence from the
      Common Sense Model of Self-Regulation. RESULTS: The majority of participants
      relied on SMBG to evaluate their self-management efforts. Key themes included:
      adopting an experimental approach; experiencing 'a-ha' moments; provider-assisted
      problem-solving; using SMBG and other feedback to evaluate when their efforts
      were working; and normalizing diabetes-specific behaviour changes as being
      healthy for everyone. CONCLUSIONS: Our qualitative data are consistent with the
      argument that SMBG, if implemented appropriately with enough education and
      provider access, can be a powerful tool for non-insulin-treated adults with Type
      2 diabetes to monitor their self-management. Establishing sufficient conditions
      for illness coherence to develop while individuals are learning to use SMBG could
      increase their sense of personal control in managing a complex and demanding
      illness.

PMID- 25764082
TI  - Magnesium with micro-arc oxidation coating and polymeric membrane: an in vitro
      study on microenvironment.
AB  - Numerous modification methods have been reported to enhance the corrosion
      resistance of magnesium with positive results. However, little attention has been
      paid on their impact on micro-environment, particularly the ion concentration and
      local pH value. In this study, two different coatings were prepared on magnesium,
      one with porous micro-arc oxidation (MAO) coating alone, and the other with
      additional polymer polyhydroxybutyrate (PHB) membrane using spinning technique.
      Their in vitro corrosional and biological behaviors were investigated and
      compared. Both coatings were found to reduce the degradation rate of magnesium,
      but an additionally deposited PHB membrane was superior to MAO-coated magnesium
      since it could produce a micro-environment with preferable local pH value and ion
      concentration for osteoblast proliferation. Our study suggests that micro
      environment should be another critical issue in evaluation of a modification
      method for orthopaedic implants. 

PMID- 25764083
TI  - Green synthesis of bimetallic Au@Pt nanostructures and their application for
      proliferation inhibition and apoptosis induction in human cervical cancer cell.
AB  - Bimetallic Au@Pt nanostructures (Au@Pts) are potential candidates for optical,
      electrical, catalytic and biological applications. However, methods for the
      fabrication of Au@Pts using total tea polyphenols (TPPs), studies of the
      mechanism of action of Au@Pts on biological systems and studies on the
      application of Au@Pts in cancer diagnosis and therapy are sparse. In this study,
      we developed a simple, eco-friendly and low-cost method for the synthesis of
      Au@Pts to examine the cytotoxic effect of these Au@Pts on human cervical cancers
      in vitro. The gold and platinum ions were successfully reduced simultaneously
      using TPPs at room temperature. The prepared Au@Pts were characterized using UV
      Vis spectrophotometery, X-ray diffractometery (XRD), energy-dispersive X-ray
      spectroscopy (EDS), and transmission electron microscopy (TEM). EDS and XRD
      confirmed the formation of the Au@Pt. Formation of Au@Pts with a size of 5-20 nm
      was confirmed using TEM. The cytotoxic properties of the Au@Pts were evaluated in
      human cervical cancer cells (SiHa). The cell viability results revealed that
      Au@Pts induce cell death in a dose- and time-dependent manner. The morphological
      features of the Au@Pt-exposed SiHa cells were observed and indicated cell death
      via cell shrinkage, intranucleosomal DNA fragmentation and chromatin
      condensation. During progression of the different phases of the cell cycle, the
      proportion of cells in the G2/M phase of the treated SiHa cells was significantly
      increased, which strongly confirmed that the Au@Pts induced apoptosis through the
      G2/M phase check points. Our findings demonstrate the activity of Au@Pts against
      cervical cancer cells and reveal strategies for the development of highly active
      bimetallic nanostructures for cancer therapeutics.

PMID- 25764084
TI  - Novel implantable composite biomaterial by fibrin glue and amniotic membrane for
      ocular surface reconstruction.
AB  - Amniotic membrane transplantation (AMT) is considered a substantial treatment
      option in the management of ocular surface disorders. However, several inherent
      drawbacks still remain. The present study devised a novel implantable composite
      biomaterial of fibrin glue-double layer Amniotic membrane (AM) and evaluated the
      biomechanical properties and effects on corneal surface reconstruction in alkali
      burned rabbit model. Biomechanic parameters were calculated by an electronic
      universal testing machine. Corneal alkali burning was done in the right eyes of
      thirty rabbits, which were randomized into three groups of ten animals each. The
      eyes in group 1 underwent fibrin glue-double layer AMT, the eyes in group 2
      underwent ordinary single layer AMT, and the eyes in group 3 (control group) did
      not undergo any surgical procedure. Healing of corneal epithelial defect, extent
      of corneal vascularization and corneal clarity were assessed and compared at two
      time points. One month after surgery, animals were killed and the eyes were
      processed for histopathology. The fibrin glue-double layer AM composites had more
      ideal biomechanical properties. In fibrin glue-double layer AM group, the rate of
      epithelial healing, vascularization inhibition and corneal clarity was
      significantly better than the other two groups. Novel fibrin glue-double layer
      AMT with corneal alkali burns is more effective and useful for ocular surface
      reconstruction and has great potential applications. 

PMID- 25764085
TI  - Insect-flower interaction network structure is resilient to a temporary pulse of
      floral resources from invasive Rhododendron ponticum.
AB  - Invasive alien plants can compete with native plants for resources, and may
      ultimately decrease native plant diversity and/or abundance in invaded sites.
      This could have consequences for native mutualistic interactions, such as
      pollination. Although invasive plants often become highly connected in plant
      pollinator interaction networks, in temperate climates they usually only flower
      for part of the season. Unless sufficient alternative plants flower outside this
      period, whole-season floral resources may be reduced by invasion. We hypothesized
      that the cessation of flowering of a dominant invasive plant would lead to
      dramatic, seasonal compositional changes in plant-pollinator communities, and
      subsequent changes in network structure. We investigated variation in floral
      resources, flower-visiting insect communities, and interaction networks during
      and after the flowering of invasive Rhododendron ponticum in four invaded Irish
      woodland sites. Floral resources decreased significantly after R. ponticum
      flowering, but the magnitude of the decrease varied among sites. Neither insect
      abundance nor richness varied between the two periods (during and after R.
      ponticum flowering), yet insect community composition was distinct, mostly due to
      a significant reduction in Bombus abundance after flowering. During flowering R.
      ponticum was frequently visited by Bombus; after flowering, these highly mobile
      pollinators presumably left to find alternative floral resources. Despite
      compositional changes, however, network structural properties remained stable
      after R. ponticum flowering ceased: generality increased, but quantitative
      connectance, interaction evenness, vulnerability, H'2 and network size did not
      change. This is likely because after R. ponticum flowering, two to three
      alternative plant species became prominent in networks and insects increased
      their diet breadth, as indicated by the increase in network-level generality. We
      conclude that network structure is robust to seasonal changes in floral abundance
      at sites invaded by alien, mass-flowering plant species, as long as alternative
      floral resources remain throughout the season to support the flower-visiting
      community. 

PMID- 25764086
TI  - Relationship between sperm apoptosis and bull fertility: in vivo and in vitro
      studies.
AB  - The objectives of this study were to confirm the relationship of apoptosis
      associated membrane and nuclear changes in bull spermatozoa with field fertility,
      to predict the fertility of beef bulls used for natural breeding and to study the
      role of DNA-nicked spermatozoa in early embryonic development. In Experiment 1,
      the relationship between fertility and different sperm populations identified by
      the Annexin V/propidium iodide (PI) and terminal deoxynucleotidyl transferase
      mediated dUTP nick end labeling (TUNEL) assays was determined. Bull fertility was
      related to live (PPPin vitro cleavage and blastocyst rates was evaluated, using
      30000 or 300000 spermatozoa per droplet. Cleavage rate was adversely affected
      (PP<0.05) in high DNA-nicked spermatozoa at the lower sperm concentration. In
      conclusion, the incidence of DNA-nicked spermatozoa is a useful marker to predict
      a bull's fertility potential. DNA-nicked spermatozoa showed adverse effects on
      early embryonic development.

PMID- 25764087
TI  - Clinical significance of immunotherapy with combined three kinds of cells for
      operable colorectal cancer.
AB  - Surgery, chemotherapy, and radiotherapy have presented with the ability of
      killing tumor cells, as well as damaging the immune function, which can be
      corrected by the immunotherapy. The purpose of this perspective cohort study was
      to evaluate the efficacy of postoperative immunotherapies of tumor lysate-loaded
      dendritic cells (DC), in vitro DC-activated T (DC-AT), and activated T cells
      (ATC) combined with chemotherapy on the survival of patients with operable
      colorectal cancer. A total of 253 patients with primary colorectal cancer
      resection including 181 patients receiving postoperative simple chemotherapy
      (control group) and 72 patients receiving immunotherapies of DC, DC-AT, and ATC
      combined with chemotherapy during the corresponding period (immunotherapy group)
      were enrolled in this perspective cohort study. The survival of these patients
      was analyzed. The immunotherapy group presented a higher 5-year overall survival
      rate than the control group (75.63 vs 67.81 %, P = 0.035), as well as 3-year
      overall survival rate (87.07 vs 74.80 %, P = 0.045). For patients with advanced
      cancer (TNM stages III and IV), immunotherapy significantly promotes mean
      survival than control subjects (59.74 +/- 3.21 vs 49.99 +/- 2.54 years, P =
      0.034). Patients who received more than three cycles of immunotherapies had a
      higher 5-year overall survival rate than those with less than three cycles (82.10
      vs 69.90 %, P = 0.035). No serious adverse effect was observed in the
      immunotherapy group. Postoperative immunotherapies with DC, DC-AT, and ATC
      combination can promote the survival of patients with operable colorectal cancer
      (Clinical Trials, ChiCTR-OCH-12002610).

PMID- 25764088
TI  - Patient satisfaction with coronary CT angiography, myocardial CT perfusion,
      myocardial perfusion MRI, SPECT myocardial perfusion imaging and conventional
      coronary angiography.
AB  - OBJECTIVES: To evaluate patient acceptance of noninvasive imaging tests for
      detection of coronary artery disease (CAD), including single-photon emission
      computed tomography myocardial perfusion imaging (SPECT-MPI), stress perfusion
      magnetic resonance imaging (MRI), coronary CT angiography (CTA) in combination
      with CT myocardial stress perfusion (CTP), and conventional coronary angiography
      (CCA). METHODS: Intraindividual comparison of perception of 48 patients from the
      CORE320 multicentre multinational study who underwent rest and stress SPECT-MPI
      with a technetium-based tracer, combined CTA and CTP (both with contrast agent,
      CTP with adenosine), MRI, and CCA. The analysis was performed by using a
      validated questionnaire. RESULTS: Patients had significantly more concern prior
      to CCA than before CTA/CTP (p < 0.001). CTA/CTP was also rated as more
      comfortable than SPECT-MPI (p = 0.001). Overall satisfaction with CT was superior
      to that of MRI (p = 0.007). More patients preferred CT (46%; p < 0.001) as a
      future diagnostic test. Regarding combined CTA/CTP, CTP was characterised by
      higher pain levels and an increased frequency of angina pectoris during the
      examination (p < 0.001). Subgroup analysis showed a higher degree of pain during
      SPECT-MPI with adenosine stress compared to physical exercise (p = 0.016).
      CONCLUSIONS: All noninvasive cardiac imaging tests are well accepted by patients,
      with CT being the preferred examination. KEY POINTS: * A variety of cardiac
      imaging tests is available without known patient preference * CTA/CTP shows a
      lower degree of concern than conventional coronary angiography * CTA/CTP shows
      higher overall satisfaction compared to stress perfusion magnetic resonance
      imaging * CTA/CTP is rated as more comfortable than SPECT-MPI * CTA/CTP is the
      preferred cardiac imaging test.

PMID- 25764089
TI  - Transient health symptoms of MRI staff working with 1.5 and 3.0 Tesla scanners in
      the UK.
AB  - OBJECTIVES: Recent studies have consistently shown that amongst staff working
      with MRI, transient symptoms directly attributable to the MRI system including
      dizziness, nausea, tinnitus, and concentration problems are reported. This study
      assessed symptom prevalence and incidence in radiographers and other staff
      working with MRI in healthcare in the UK. METHODS: One hundred and four volunteer
      staff from eight sites completed a questionnaire and kept a diary to obtain
      information on subjective symptoms and work practices, and wore a magnetic field
      dosimeter during one to three randomly selected working days. Incidence of MRI
      related symptoms was obtained for all shifts and prevalence of MRI-related and
      reference symptoms was associated to explanatory factors using ordinal
      regression. RESULTS: Incident symptoms related to working with MRI were reported
      in 4% of shifts. Prevalence of MRI-related, but not reference symptoms were
      associated with number of hours per week working with MRI, shift length, and
      stress, but not with magnetic field strength (1.5 and 3 T) or measured magnetic
      field exposure. CONCLUSIONS: Reporting of prevalent symptoms was associated with
      longer duration of working in MRI departments, but not with measured field
      strength of exposure. Other factors related to organisation and stress seem to
      contribute to increased reporting of MRI-related symptoms. KEY POINTS: * Routine
      work with MRI is associated with increased reporting of transient symptoms * No
      link to the strength of the magnetic field was demonstrated. * Organisational
      factors and stress additionally contribute to reporting of MRI-related symptoms.

PMID- 25764090
TI  - Increased epicardial fat is independently associated with the presence and
      chronicity of atrial fibrillation and radiofrequency ablation outcome.
AB  - OBJECTIVE: To determine whether intrathoracic fat volumes are associated with
      presence and chronicity of atrial fibrillation (AF) and radiofrequency ablation
      (RFA) treatment outcome. METHODS: IRB approval was obtained and patient consent
      was waived for this HIPAA-compliant retrospective study. 169 patients with AF (75
      non-paroxysmal and 94 paroxysmal) and 62 control patients underwent cardiac CT
      examination. Extrapericardial (EPFV) and epicardial fat volumes (EFV) were
      measured on CT, the sum of which is the total intrathoracic fat volume.
      Associations between these three fat volumes and presence and chronicity of AF,
      and outcome after RFA, were evaluated using logistic regression analysis.
      RESULTS: EFV was significantly associated with presence [OR 1.01 (95 % CI 1.003
      1.03), p = 0.01], chronicity of AF [1.008 (1.001-1.020), p = 0.03] and AF
      recurrence after RFA [1.009 (1.001-1.01), p = 0.02] after adjustment for age,
      gender and BMI. Patients with a larger EFV had a shorter time to AF recurrence (p
      = 0.017) and a higher rate of recurrence (54 % vs 46 %) (p = 0.002) after RFA.
      EPFV had no significant associations. CONCLUSION: Increased epicardial fat is
      associated with the presence and chronicity of AF, a higher probability of AF
      recurrence after RFA and a shorter AF-free interval. KEY POINTS: * Increased
      epicardial fat is associated with presence and chronicity of atrial fibrillation
      * Extensive epicardial fat is associated with earlier recurrences of AF after
      ablation * Extensive epicardial fat may reduce transmurality of ablation by
      affecting current dynamics.

PMID- 25764091
TI  - Predictive Accuracy of the PanCan Lung Cancer Risk Prediction Model -External
      Validation based on CT from the Danish Lung Cancer Screening Trial.
AB  - OBJECTIVES: Lung cancer risk models should be externally validated to test
      generalizability and clinical usefulness. The Danish Lung Cancer Screening Trial
      (DLCST) is a population-based prospective cohort study, used to assess the
      discriminative performances of the PanCan models. METHODS: From the DLCST
      database, 1,152 nodules from 718 participants were included. Parsimonious and
      full PanCan risk prediction models were applied to DLCST data, and also
      coefficients of the model were recalculated using DLCST data. Receiver operating
      characteristics (ROC) curves and area under the curve (AUC) were used to evaluate
      risk discrimination. RESULTS: AUCs of 0.826-0.870 were found for DLCST data based
      on PanCan risk prediction models. In the DLCST, age and family history were
      significant predictors (p = 0.001 and p = 0.013). Female sex was not confirmed to
      be associated with higher risk of lung cancer; in fact opposing effects of sex
      were observed in the two cohorts. Thus, female sex appeared to lower the risk (p
      = 0.047 and p = 0.040) in the DLCST. CONCLUSIONS: High risk discrimination was
      validated in the DLCST cohort, mainly determined by nodule size. Age and family
      history of lung cancer were significant predictors and could be included in the
      parsimonious model. Sex appears to be a less useful predictor. KEY POINTS: * High
      accuracy in logistic modelling for lung cancer risk stratification of nodules. *
      Lung cancer risk prediction is primarily based on size of pulmonary nodules. *
      Nodule spiculation, age and family history of lung cancer are significant
      predictors. * Sex does not appear to be a useful risk predictor.

PMID- 25764092
TI  - Lateral MI Explains the Presence of Prominent R Wave (R >= S) in V1.
AB  - AIMS: It is necessary to clarify if the presence of a prominent R wave in V1, in
      post-myocardial infarction (MI) patients, is due to the involvement of the
      posterior wall (currently inferobasal segment) or the lateral wall (as has been
      demonstrated recently by electrocardiographic contrast-enhanced cardiac magnetic
      resonance [ECG-CE-CMR] correlations studies). METHODS: In 155 patients with
      inferolateral zone MI, as detected by CE-CMR, the following ECG parameters were
      evaluated and correlated with MI location according to CE-CMR: R/S ratio in V1 >=
      1 (classic criteria for posterior MI), R/S ratio in V1 >= 0.5, and R in V1 >= 3
      mm. RESULTS: R/S >= 1 criterion: Present in 20 cases: 3 of lateral MI, 17 of
      inferolateral MI, 0 of inferior MI. Absent in 135 cases, 81 of
      lateral/inferolateral MI (28/53), 54 of inferior MI (SE 19.8%, SP 100%). R/S >=
      0.5 criterion: Present in 47 cases: 6 of lateral MI, 39 of inferolateral MI, 2 of
      inferior MI. Absent in 108 cases, 56 of lateral/inferolateral MI (25/31), 52 of
      inferior MI (SE 44.6%, SP 96.4%). R >= 3 mm criterion: Present in 30 cases: 5 of
      IM lateral, 23 of inferolateral MI, 2 of inferior MI. Absent in 125 cases, 73
      lateral/inferolateral MI (26/47), 52 inferior MI (SE 27.7%, SP 96.4%).
      CONCLUSIONS: The presence of prominent the R wave in V1 is due to the lateral MI
      and not to the involvement of inferobasal segment of inferior wall (old posterior
      wall).

PMID- 25764093
TI  - The Effects of Hyper- and Hypocapnia on Phonatory Laryngeal Airway Resistance in
      Women.
AB  - PURPOSE: The larynx has a dual role in the regulation of gas flow into and out of
      the lungs while also establishing resistance required for vocal fold vibration.
      This study assessed reciprocal relations between phonatory functions
      specifically, phonatory laryngeal airway resistance (Rlaw)-and respiratory
      homeostasis during states of ventilatory gas perturbations. METHOD: Twenty-four
      healthy women performed phonatory tasks while exposed to induced hypercapnia
      (high CO2), hypocapnia (low CO2), and normal breathing (eupnea). Effects of gas
      perturbations on Rlaw were investigated as were the reciprocal effects of Rlaw
      modulations on respiratory homeostasis. RESULTS: Rlaw remained stable despite
      manipulations of inspired gas concentrations. In contrast, end-tidal CO2 levels
      increased significantly during all phonatory tasks. Thus, for the conditions
      tested, Rlaw did not adjust to accommodate ventilatory needs as predicted.
      Rather, stable Rlaw was spontaneously accomplished at the cost of those needs.
      CONCLUSIONS: Findings provide support for a theory of regulation wherein Rlaw may
      be a control parameter in phonation. Results also provide insight into the
      influence of phonation on respiration. The work sets the foundation for future
      studies on laryngeal function during phonation in individuals with lower airway
      disease and other patient populations.

PMID- 25764094
TI  - Seroprevalence of pertussis in the Gambia: evidence for continued circulation of
      bordetella pertussis despite high vaccination rates.
AB  - BACKGROUND: Bordetella pertussis can cause severe respiratory disease and death
      in children. In recent years, large outbreaks have occurred in high-income
      countries; however, little is known about pertussis incidence in sub-Saharan
      Africa. METHODS: We evaluated antibody responses to pertussis toxin (Ptx) from
      individuals aged between 2 and 90 years in rural Gambia. IgG-Ptx was measured
      using luminex xMAP technology. IgG-Ptx geometric mean concentrations (GMC) and
      their 95% confidence intervals were calculated. The proportion seropositive (>20
      EU/mL or >=62.5 EU/mL) and GMCs were compared by age, sex, ethnic group,
      vaccination status, birth order and number of siblings per household using
      logistic and linear regression. RESULTS: 76.3% had anti-Ptx levels <20 EU/mL,
      17.5% had concentrations between 20 and 62.5 EU/mL, 4.4% had concentrations
      between 62.5 and 125 EU/mL and 1.8% had concentrations >=125 EU/mL. The overall
      Ptx antibody GMC was 6.4 EU/mL (95% confidence interval: 5.8-6.9). Higher
      antibody concentrations were observed in older populations with evidence for an
      increase in infection risk with increasing age (1.9% yearly increase, 95%
      confidence interval: 1.3-2.5). No child under 6 years of age had GMC above 62.5
      EU/mL but 29.5% had concentrations between 20 and 62.5 EU/mL. CONCLUSIONS: These
      data provide evidence that B. pertussis is being transmitted within this
      population despite high vaccination coverage. Re-infection may occur implying
      that immunity from childhood vaccination may not be lifelong. In the absence of
      data on actual clinical cases of pertussis, seroprevalence studies remain
      valuable tools to assess the transmission dynamics of B. pertussis.

PMID- 25764095
TI  - Ethambutol-related impaired visual function in childrens less than 5 years of age
      treated for a mycobacterial infection: diagnosis and evolution.
AB  - BACKGROUND: The effects of ethambutol (EMB) on vision are particularly difficult
      to detect in children less than 5 years of age because of a lack of complaints
      and objective clinical signs. The aim of this study was to assess the frequency
      of visual abnormalities and the utility of visual-evoked potentials (VEPs)
      recordings in monitoring the visual function of children less than 5 years of age
      who were exposed to EMB during anti-mycobacterial treatment. METHODS: We
      performed a retrospective study in Robert-Debre University Hospital, Paris,
      France, including all children less than 5 years of age, who were treated with
      EMB for a mycobacterial infection from January 2002 to December 2012. RESULTS:
      Fourteen patients were enrolled, including 12 treated for Mycobacterium
      tuberculosis infection. The sex ratio was 1:1. The median age was 1.65 years (0.3
      to 4.7). Five patients had subarachnoid involvement. The median EMB dose was 22
      mg/kg/day (15 to 27). Only 11 patients were monitored using VEPs. Three children
      (27.3%) developed a visual impairment secondary to EMB, with delays of 4, 7 and
      36 weeks. One of the 3 patients developed an impairment of the retrochiasmatic
      visual pathways, and 2 other patients developed classical retrobulbar optic
      neuritis. In all cases, the discontinuation of EMB resulted in a normalization of
      these findings. CONCLUSION: Alterations in visual function related to the use of
      EMB are not uncommon in young children and are most likely underestimated.
      Systematic close monitoring using VEPs recordings is needed in young children
      treated with EMB.

PMID- 25764096
TI  - A prospective controlled trial of the optimal volume for neonatal blood cultures.
AB  - BACKGROUND: Bacteremia is a frequent complication in neonatal intensive care
      units. Blood cultures are the standard for the diagnosis. It is a common practice
      to draw small blood volumes for culture from neonates in order to prevent anemia;
      however, this might compromise the test sensitivity. We examined whether using 1
      mL of blood in a single aerobic bottle would improve the culture yield compared
      with our current practice of obtaining 2 samples of 0.5 mL of blood (aerobic and
      anaerobic bottles). METHODS: A prospective controlled study was conducted between
      December 2009 and September 2010 at the neonatal intensive care unit of Shaare
      Zedek Medical Center, Jerusalem, Israel. Study population included newborns from
      whom blood cultures were obtained. A sample of 2 mL of blood from each patient
      was divided into a single aerobic bottle (1 mL; study sample) and into 2 aerobic
      and anaerobic bottles (0.5 mL each; control samples). Culture bottles were
      weighed before and after blood inoculation and time to positivity (TTP) was
      recorded. RESULTS: We obtained 706 complete culture sets from 519 patients.
      Pathogens grew in 72 (10.2%) cultures from 37 patients. Isolation of organisms
      was significantly higher in the 0.5 mL control group (94.4% vs. 77.7%, P =
      0.012). The TTP was similar in 0.5 mL and 1 mL aerobic bottles, but significantly
      longer in the anaerobic bottle. CONCLUSIONS: Allocating 1 mL of blood into 2
      bottles, aerobic and anaerobic, improved the yield of the culture compared with 1
      mL in a single aerobic bottle.

PMID- 25764097
TI  - Acute otorrhea in children with tympanostomy tubes: prevalence of bacteria and
      viruses in the post-pneumococcal conjugate vaccine era.
AB  - BACKGROUND: Acute tympanostomy-tube otorrhea is a common sequela in children with
      tympanostomy tubes. Acute tympanostomy-tube otorrhea is generally a symptom of an
      acute middle ear infection, whereby middle ear fluid drains through the tube. The
      widespread use of pneumococcal conjugate vaccination (PCV) has changed the
      bacterial prevalence in the upper respiratory tract of children, but its impact
      on bacterial and viral pathogens causing acute tympanostomy-tube otorrhea is yet
      unknown. METHODS: This study was performed in the post-PCV7 era parallel to a
      randomized clinical trial of the clinical and cost-effectiveness of ototopical
      and systemic antibiotics and initial observation in 230 children aged 1 to 10
      years with untreated, uncomplicated acute tympanostomy-tube otorrhea. Otorrhea
      and nasopharyngeal samples were collected at baseline (before treatment) and at 2
      weeks (after treatment). Conventional bacterial culture was performed followed by
      antimicrobial-resistance assessment. Viruses were identified by polymerase chain
      reaction. RESULTS: At baseline, Haemophilus influenzae (41%), Staphylococcus
      aureus (40%) and Pseudomonas aeruginosa (18%) were the most prevalent bacteria in
      otorrhea, followed by Streptococcus pneumoniae (7%) and Moraxella catarrhalis
      (4%). Most pneumococci were non-PCV7 serotypes. Viruses were detected in 45
      otorrhea samples at baseline (21%). Most infections were polymicrobial and
      overall antimicrobial resistance was low. CONCLUSIONS: H. influenzae, S. aureus
      and P. aeruginosa are the most common microorganisms in children with untreated
      uncomplicated acute tympanostomy-tube otorrhea. Prevalence of S. pneumoniae has
      decreased since the introduction of PCV and most pneumococci are nonvaccine
      serotypes.

PMID- 25764098
TI  - Differential impact of pneumococcal conjugate vaccines on bacteremic pneumonia
      versus other invasive pneumococcal disease.
AB  - BACKGROUND: Bacteremic pneumonia (BP) accounts for ~35% of invasive pneumococcal
      disease (IPD) in young children. Our aims were to compare age, seasonal and
      serotype distribution of BP versus non-BP IPD and to determine whether the impact
      of the sequential 7/13-valent pneumococcal conjugate vaccine (PCV7/PCV13)
      introduction on disease incidence differed between BP and non-BP IPD in children
      <5 years of age. METHODS: A nationwide, prospective, population-based, active
      surveillance (July 2004-June 2013) was conducted. All IPD episodes were included.
      PCV7 was introduced to the Israeli National Immunization Plan in July 2009 and
      has been replaced by PCV13 since November 2010. RESULTS: In all, 983 (36.8%) BP
      and 1687 (63.2%) non-BP IPD episodes were recorded. A higher proportion of BP
      than that of non-BP IPD episodes (42.0% vs. 20.7%; P < 0.001) occurred in
      children >24 months old. Seasonality differed between BP and non-BP IPD, with
      yearly earlier peaks of non-BP IPD. The proportion of the 5 additional PCV13
      serotypes (1, 3, 5, 7F and 19A) was higher in children with BP versus non-BP IPD
      (39.6% vs. 23.6%; P < 0.01). Shortly after PCV7 introduction, non-BP IPD rate was
      significantly reduced but that of BP was not. However, PCV13 introduction
      resulted in rapid reduction of BP rate, with a further reduction of non-BP IPD.
      CONCLUSION: The differences in age distribution, seasonality and serotype
      distribution between BP and non-BP IPD suggest that the pathogenesis of these 2
      entities is not identical and resulted in different impact rate dynamics after
      PCV7 and PCV13 introduction.

PMID- 25764099
TI  - Modeling the long-term persistence of hepatitis A antibody after a two-dose
      vaccination schedule in Argentinean children.
AB  - BACKGROUND: Long-term seroprotection data are essential for decision-making on
      the need and timing of vaccine boosters. Based on data from longitudinal
      serological studies, modeling can provide estimates on long-term antibody
      persistence and inform such decision-making. METHODS: We examined long-term anti
      hepatitis A virus (anti-HAV) antibody persistence in Argentinean children <=15
      years after the initial study where they completed a 2-dose course of inactivated
      hepatitis A vaccine (Avaxim 80U Pediatric, Sanofi Pasteur, Lyon, France). Blood
      serum samples were taken at baseline, 2 weeks (post first dose), 6 months (pre
      booster), 6.5 months (post-booster), 10 years and 14-15 years after first vaccine
      dose. We fitted 8 statistical model types, predominantly mixed effects models, to
      anti-HAV persistence data, to identify the most appropriate and best fitting
      models for our data set and to predict individuals' anti-HAV levels and
      seroprotection rates up to 30 years post vaccination. RESULTS: Fifty-four
      children (mean age at enrollment 30.4 months) were enrolled up to 15 years post
      first vaccine dose. There were 3 distinct periods of antibody concentration:
      rapid rise up to peak concentration post-booster, rapid decay from post-booster
      to 10 years, followed by slower decay. A 3-segmented linear mixed effects model
      was the most appropriate for the data set. Extrapolating based on the available
      14-15-year follow-up, the analysis predicted that 88% of individuals anti-HAV
      seronegative prior to vaccination would remain seroprotected at 30 years post
      vaccination and lifelong seroprotection for vaccinees seropositive prior to
      vaccination. CONCLUSIONS: Currently available data demonstrate that Avaxim 80U
      Pediatric confers to most vaccinees a high level of seroprotection against
      hepatitis A infection for at least 20-30 years.

PMID- 25764100
TI  - Evaluation of endothelium functions by flow-mediated dilatation in pediatric
      patients with Crimean-Congo hemorrhagic fever.
AB  - BACKGROUND: Crimean-Congo hemorrhagic fever (CCHF) is a systemic viral disease
      that also affects the endothelium. Thrombocytopenia and hemorrhage are seen in
      this disease. But, the cause of thrombocytopenia is not clear. We hypothesized
      that endothelium dysfunction may be the cause of thrombocytopenia. We evaluated
      the endothelium functions by flow-mediated dilatation (FMD) in CCHF. METHODS:
      Consecutive children with suspected CCHF who applied to our hospital were
      evaluated for recruitment into the study. FMD analysis was done in the active and
      healing period of the disease. Diagnosis was confirmed or ruled out by polymerase
      chain reaction and/or ELISA test. Basal brachial artery diameter (BBAD) and
      dilated brachial artery diameter (DBAD) after ischemic period were measured and
      percent dilatations [(DBAD-BBAD)/BBAD, FMD%] were computed from all subjects.
      RESULTS: Fifty-four children (40 male, mean age 12.4 +/- 4.4 years) were
      recruited into the study. CCHF diagnosis was confirmed in 28 children and ruled
      out in 26 children. Groups were similar for age and gender. FMD% was
      significantly decreased in CCHF patients when comparing this with the control
      patients in the active period (2.65 +/- 2.76 vs. 13.76 +/- 7.95, P < 0.001). FMD%
      was correlated with platelet count in the active period of the disease (r =
      0.599, P = 0.004). FMD% was recovered in the healing period (2.65 +/- 2.76 vs.
      14.72 +/- 2.66, P < 0.001) and was not significantly different from basal values
      of control patients (P > 0.05). CONCLUSIONS: FMD is significantly decreased in
      CCHF and recovers in the healing period. So, endothelium functions are disturbed,
      and disturbance is correlated with thrombocytopenia in CCHF.

PMID- 25764101
TI  - Nail findings in hand-foot-and-mouth disease.
AB  - Hand-foot-and-mouth disease (HFMD) is a common self-limited viral illness seen in
      the United States and around the world. Its classic features are easily
      recognizable; however, nail changes are not well known or characterized. This
      case demonstrates onychomadesis and Beau lines in a child following clinical
      diagnosis of hand-foot-and-mouth disease. In this setting, nail dystrophies
      should be reassuring to pediatricians and families.

PMID- 25764102
TI  - Prevalence and clinical burden of NDM-1 positive infections in pediatric and
      neonatal patients in Pakistan.
AB  - In a neonatal/pediatric Gram-negative infection study from Islamabad, 71/82
      strains were carbapenem resistant with 12/82 positive for New Delhi Metallo-beta
      lactamase and many being extensively antibiotic resistant. Burden and outcome
      analysis on 9 patients showed that 4/9 died after inadequate therapy regardless
      of organism type.

PMID- 25764103
TI  - Clinical and microbiologic outcomes of quinolone prophylaxis in children with
      acute myeloid leukemia.
AB  - BACKGROUND: Intensifying treatment for pediatric acute myeloid leukemia (AML) has
      improved survival, with infections now being a leading cause of morbidity.
      Because quinolone prophylaxis is effective in adults with AML and in transplant
      populations, ciprofloxacin prophylaxis (CPx) was introduced as the standard for
      pediatric AML. We report here the impact of CPx in this population. METHODS:
      Prevalence of fever and neutropenia, frequency and pathogen spectrum of
      infections, antibiotic use, supportive care and mortality before and after
      implementation of CPx were retrospectively compared in children with AML.
      RESULTS: The cohort included 35 patients with de novo and 10 with relapsed AML,
      who together underwent 153 chemotherapy courses. Fever and neutropenia resulting
      in the use of empiric antibiotics occurred in 90% of chemotherapy courses
      (137/153); this was associated with proven bacteremia in 26%. The use of CPx did
      not change the incidence of febrile or infectious episodes, number of days of
      fever or antibiotic treatment or mortality. CPx was associated with a significant
      decrease in infections caused by Gram-negative rods (13.4% vs 4.7%) but a
      concomitant significant increase in bacteremia caused by viridans streptococci
      (12% vs 28%), resulting in no significant overall difference in the incidence of
      bacteremia between the 2 groups (35.9% vs 31.5%). CONCLUSIONS: CPx neither alter
      the incidence of overall bacteremia nor change the pattern of fever or use of
      supportive care. Our experience supports further investigation into the use of
      extended-spectrum quinolone prophylaxis during therapy for pediatric AML.

PMID- 25764104
TI  - Primary osteomyelitis of the sternum in the pediatric age group: report of a new
      case and comprehensive analysis of seventy-four cases.
AB  - Pediatric primary osteomyelitis of the sternum may have a non-specific onset and
      be diagnosed late. We analyzed all accessible published cases (n = 73) and 1 new
      case in order to describe presenting signs and symptoms, laboratory findings,
      diagnostic imaging features, causative pathogens, treatments, complications and
      outcomes. This analysis represents the first comprehensive description of the
      natural history of this rare infection. 

PMID- 25764105
TI  - Using discrete choice modeling to evaluate the preferences and willingness to pay
      for leptospirosis vaccine.
AB  - Leptospirosis is highly endemic in the Philippines and a serious concern to
      public health. Local research on candidate vaccine is moving through the
      development pipeline. The availability of vaccines alone does not guarantee
      acceptance because individuals' vaccination choice decision is influenced by
      several factors. This study assessed how vaccine attributes and socio-demographic
      factors affect the acceptability of leptospirosis vaccine; and estimated
      individuals' willingness to pay for leptospirosis vaccine. A discrete choice
      experiment was conducted among leptospirosis and non-leptospirosis case
      respondents (n = 342) living in Metro Manila. Random Parameters Logit model was
      used to estimate the relative importance of vaccine attributes and socio
      demographic variables on respondents' leptospirosis vaccination choice decision.
      The estimated model coefficients were used to derive implicit prices and
      willingness to pay for leptospirosis vaccine. Both case respondents preferred
      leptospirosis vaccine with 70-100% efficacy, mild to moderate risk of side
      effects, given in a single shot, and at a lower price. Non-leptospirosis case
      respondents preferred a vaccine with 7 to 10 y of protection, while leptospirosis
      case respondents preferred a vaccine with 10 y protection. The probability of
      leptospirosis vaccination acceptance was affected by respondents' age, education,
      family size and income, proximity of home to rivers and sewers, and leptospirosis
      awareness level. Respondents' willingness to pay for leptospirosis vaccine (US$
      31.14-US$ 65.89) was higher than the Japanese retail price (US$ 21.60-US$ 24.00).
      Our findings indicated significant potential for introducing leptospirosis
      vaccine in the Philippine vaccine market. Delivery strategies to ensure equitable
      access to future leptospirosis vaccine are recommended. 

PMID- 25764106
TI  - Acral skin atrophy in an infant: an early clue to Kindler syndrome diagnosis.

PMID- 25763955
TI  - Measurements of the Nuclear Modification Factor for Jets in Pb+Pb Collisions at
      ?(s)NN]=2.76  TeV with the ATLAS detector.
AB  - Measurements of inclusive jet production are performed in pp and Pb+Pb collisions
      at ?(s)NN=2.76  TeV with the ATLAS detector at the LHC, corresponding to
      integrated luminosities of 4.0 and 0.14  nb(-1), respectively. The jets are
      identified with the anti-k(t) algorithm with R=0.4, and the spectra are measured
      over the kinematic range of jet transverse momentum 32<p(T)<500  GeV and absolute
      rapidity |y|<2.1 and as a function of collision centrality. The nuclear
      modification factor R(AA) is evaluated, and jets are found to be suppressed by
      approximately a factor of 2 in central collisions compared to pp collisions. The
      R(AA) shows a slight increase with p(T) and no significant variation with
      rapidity.

PMID- 25764107
TI  - Treatment responsiveness in CIDP patients with diabetes is associated with unique
      electrophysiological characteristics, and not with common criteria for CIDP.
AB  - OBJECTIVES: Characterize treatment responsiveness in chronic inflammatory
      demyelinating polyradiculoneuropathy (CIDP) patients with diabetes mellitus (DM).
      METHODS: We performed a retrospective chart review of CIDP subjects assessed
      between 1997 and 2013 and compared treatment response rates in those with and
      without DM, using different sets of criteria. RESULTS: 99 CIDP patients were
      included, 34 CIDP+DM and 65 CIDP-DM patients, both having similar treatment
      response rates. CIDP patients fulfilling European Federation of Neurological
      Societies/Peripheral Nerve Society (EFNS/PNS) criteria had higher treatment
      response rates. Responders fulfilled a higher number of American Academy of
      Neurology (AAN) and EFNS/PNS criteria and had a higher number of demyelinating
      features in the total cohort and in CIDP-DM but not in CIDP+DM patients. CIDP+DM
      responders, however, had unique electrophysiologic characteristics. CONCLUSION:
      Fulfilling EFNS/PNS and AAN criteria, and higher number of demyelinating
      features, are associated with higher treatment response rates in CIDP-DM but not
      in CIDP+DM patients, implying the need for adjusting current criteria to predict
      treatment response rates in CIDP-DM patients.

PMID- 25764108
TI  - Endonasal ultrasonography-assisted neuroendoscopic transsphenoidal surgery.
AB  - We report endonasal ultrasonography (US)-assisted neuroendoscopic transsphenoidal
      surgery (TSS) in seven patients. With sagittal and coronal US images, internal
      carotid arteries, anterior cerebral arteries, residual tumor, and lateral
      ventricles were recognized, and the tumors were removed without leakage of
      cerebrospinal fluid in patients with pituitary adenoma. US images clearly
      depicted the carotid arteries, anterior cerebral arteries, middle cerebral
      arteries, chiasmatic cistern, and residual tumor. Endonasal US images can provide
      real-time animated information and may help neuroendoscopic TSS, whenever needed
      during TSS. 

PMID- 25764109
TI  - The RNA polymerase II preinitiation complex. Through what pathway is the complex
      assembled?
AB  - The general transcription factors required for the assembly of the RNA polymerase
      II preinitiation complex at TATA-dependent promoters are well known. However,
      recent studies point to two quite distinct pathways for assembly of these
      components into functional transcription complexes. In this review, the two
      pathways are compared and potential implications for gene regulatory mechanisms
      are discussed. 

PMID- 25764110
TI  - Comparative overview of RNA polymerase II and III transcription cycles, with
      focus on RNA polymerase III termination and reinitiation.
AB  - In eukaryotes, RNA polymerase (RNAP) III transcribes hundreds of genes for tRNAs
      and 5S rRNA, among others, which share similar promoters and stable transcription
      initiation complexes (TIC), which support rapid RNAP III recycling. In contrast,
      RNAP II transcribes a large number of genes with highly variable promoters and
      interacting factors, which exert fine regulatory control over TIC lability and
      modifications of RNAP II at different transitional points in the transcription
      cycle. We review data that illustrate a relatively smooth continuity of RNAP III
      initiation-elongation-termination and reinitiation toward its function to produce
      high levels of tRNAs and other RNAs that support growth and development. 

PMID- 25764112
TI  - Single molecule studies of RNA polymerase II transcription in vitro.
AB  - Eukaryotic mRNA transcription by RNA polymerase II (RNAP II) is the first step in
      gene expression and a key determinant of cellular regulation. Elucidating the
      mechanism by which RNAP II synthesizes RNA is therefore vital to determining how
      genes are controlled under diverse biological conditions. Significant advances in
      understanding RNAP II transcription have been achieved using classical
      biochemical and structural techniques; however, aspects of the transcription
      mechanism cannot be assessed using these approaches. The application of single
      molecule techniques to study RNAP II transcription has provided new insight only
      obtainable by studying molecules in this complex system one at a time. 

PMID- 25764111
TI  - Contributions of in vitro transcription to the understanding of human RNA
      polymerase III transcription.
AB  - Human RNA polymerase III transcribes small untranslated RNAs that contribute to
      the regulation of essential cellular processes, including transcription, RNA
      processing and translation. Analysis of this transcription system by in vitro
      transcription techniques has largely contributed to the discovery of its
      transcription factors and to the understanding of the regulation of human RNA
      polymerase III transcription. Here we review some of the key steps that led to
      the identification of transcription factors and to the definition of minimal
      promoter sequences for human RNA polymerase III transcription. 

PMID- 25764113
TI  - Investigating transcription reinitiation through in vitro approaches.
AB  - By influencing the number of RNA molecules repeatedly synthesized from the same
      gene, the control of transcription reinitiation has the potential to shape the
      transcriptome. Transcription reinitiation mechanisms have been mainly addressed
      in vitro, through approaches based on both crude and reconstituted systems. These
      studies support the notion that transcription reinitiation and its regulation
      rely on dedicated networks of molecular interactions within transcription
      machineries. At the same time, comparison with in vivo transcription rates
      suggests that additional mechanisms, factors and conditions must exist in the
      nucleus, whose biochemical elucidation is a fascinating challenge for future in
      vitro transcription studies. 

PMID- 25764115
TI  - Functional variations in MBL2 gene are associated with cutaneous leishmaniasis in
      the Amazonas state of Brazil.
AB  - Functional variations in the mannose-binding lectin (MBL2) gene causing low
      levels of serum MBL are associated with susceptibility to numerous infectious
      diseases. We investigated whether there is genetic association of MBL2 variant
      alleles with cutaneous leishmaniasis (CL) caused by Leishmania guyanensis. We
      used PCR-restriction fragment length polymorphism to genotype six MBL2 variants,
      three in the promoter region and three in the exon 1. An association was noted
      between the single nucleotide polymorphism -221X/Y of the MBL2 gene and CL (P=2.9
      * 10(-6); odds ratio (OR)=1.9 (1.4-2.5) consistent with the hypothesis that the 
      221X allele confers high risk to development of CL among L. guyanensis-infected
      individuals. Furthermore, L. guyanensis-infected individuals bearing the codon 57
      allele C had a higher risk of developing CL (P=5 * 10(-5); OR=1.9 (1.4-2.6)). The
      low MBL expressor haplotype LXPB was also associated to CL (P=6 * 10(-4)). This
      study raises the possibility that functional polymorphisms in MBL2 gene play a
      role in clinical outcome of Leishmania infection. 

PMID- 25764114
TI  - Transcription elongation. Heterogeneous tracking of RNA polymerase and its
      biological implications.
AB  - Regulation of transcription elongation via pausing of RNA polymerase has multiple
      physiological roles. The pausing mechanism depends on the sequence heterogeneity
      of the DNA being transcribed, as well as on certain interactions of polymerase
      with specific DNA sequences. In order to describe the mechanism of regulation, we
      introduce the concept of heterogeneity into the previously proposed alternative
      models of elongation, power stroke and Brownian ratchet. We also discuss
      molecular origins and physiological significances of the heterogeneity. 

PMID- 25764116
TI  - Diagnostic value of blood gene expression signatures in active tuberculosis in
      Thais: a pilot study.
AB  - Tuberculosis (TB) is a major global health problem. Routine laboratory tests or
      newly developed molecular detection are limited to the quality of sputum sample.
      Here we selected genes specific to TB by a minimum redundancy-maximum relevancy
      package using publicly available microarray data and determine level of selected
      genes in blood collected from a Thai TB cohort of 40 active TB patients, 38
      healthy controls and 18 previous TB patients using quantitative real-time PCR.
      FCGR1A, FCGR1B variant 1, FCGR1B variant 2, APOL1, GBP5, PSTPIP2, STAT1, KCNJ15,
      MAFB and KAZN had significantly higher expression level in active TB individuals
      as compared with healthy controls and previous TB cases (P<0.01). A mathematical
      method was applied to calculate TB predictive score, which contains the level of
      expression of seven genes and this score can identify active TB cases with 82.5%
      sensitivity and 100% specificity as compared with conventional culture
      confirmation. In addition, TB predictive scores in active TB patients were
      reduced to normal after completion of standard short-course therapy, which was
      mostly in concordant with the disease outcome. These finding suggested that blood
      gene expression measurement and TB Sick Score could have potential value in terms
      of diagnosis of TB and anti-TB treatment monitoring. 

PMID- 25764117
TI  - Rare mendelian primary immunodeficiency diseases associated with impaired NF
      kappaB signaling.
AB  - Mendelian primary immunodeficiency diseases (MPIDs) are rare disorders affecting
      distinct constituents of the innate and adaptive immune system. Although they are
      genetically heterogeneous, a substantial group of MPIDs is due to mutations in
      genes affecting the nuclear factor-kappaB (NF-kappaB) transcription pathway,
      essential for cell proliferation and cell survival and involved in innate
      immunity and inflammation. Many of these genes encode for crucial regulatory
      components of the NF-kappaB pathway and their mutations are associated with
      immunological and developmental signs somehow overlapping in patients with MPIDs.
      At present, nine different MPIDs listed in the online mendelian inheritance in
      man (OMIM) are caused by mutations in at least nine different genes strictly
      involved in the NF-kappaB pathway that result in defects in immune responses.
      Here we report on the distinct function of each causative gene, on the impaired
      NF-kappaB step and more in general on the molecular mechanisms underlining the
      pathogenesis of the disease. Overall, the MPIDs affecting the NF-kappaB
      signalosome require a careful integrated diagnosis and appropriate genetic tests
      to be molecularly identified. Their discovery at an ever-increasing rate will
      help establish a common therapeutic strategy for a subclass of immunodeficient
      patients. 

PMID- 25764119
TI  - Discovery of novel P1 groups for coagulation factor VIIa inhibition using
      fragment-based screening.
AB  - A multidisciplinary, fragment-based screening approach involving protein ensemble
      docking and biochemical and NMR assays is described. This approach led to the
      discovery of several structurally diverse, neutral surrogates for cationic factor
      VIIa P1 groups, which are generally associated with poor pharmacokinetic (PK)
      properties. Among the novel factor VIIa inhibitory fragments identified were aryl
      halides, lactams, and heterocycles. Crystallographic structures for several bound
      fragments were obtained, leading to the successful design of a potent factor VIIa
      inhibitor with a neutral lactam P1 and improved permeability. 

PMID- 25764118
TI  - Active surveillance for low-risk prostate cancer.
AB  - There is ample evidence that low risk and many cases of low-/intermediate-risk
      prostate cancer, are indolent, have little or no metastatic potential, and do not
      pose a threat to the patient in his lifetime. Major strides have been made in
      understanding who these patients are and in encouraging the use of conservative
      management in such individuals. A component of conservative management is the
      early identification of those 'low-risk' patients who harbour higher risk
      disease, and benefit from definitive therapy. This represents about 30% of newly
      diagnosed low-risk patients. A further small proportion of patients with low-risk
      disease demonstrate biological progression to higher grade disease. Men with
      lower risk disease can defer treatment, in most cases for life. Men with higher
      risk disease that can be localized to a relatively small volume of the prostate
      can undergo selective therapy. The results of active surveillance, embodying
      conservative management with selective delayed intervention for the subset who
      are re-classified as higher risk overtime based on repeat biopsy, imaging or
      biomarker results have shown that this approach is safe in the intermediate to
      long term, with a 3% cancer specific mortality at 10-15 years. Further refinement
      of the surveillance approach is ongoing, incorporating MRI, targeted biopsies and
      molecular biomarkers.

PMID- 25764122
TI  - The role of speaking styles in assessing intonation in foreign accent syndrome.
AB  - PURPOSE: This paper evaluates the role of different speaking styles in defining
      intonation patterns in speakers with foreign accent syndrome. The methodological
      investigation aimed at establishing to what extent scripted and unscripted speech
      influence the phonological realization of intonation in disordered speech.
      METHOD: Four individuals with foreign accent syndrome and four gender-, age- and
      original dialect-matched control speakers were asked to perform a series of
      scripted and unscripted speech tasks including short sentences, a reading
      passage, a picture description and a monologue task. The speech data were
      analysed within the autosegmental-metrical framework of intonational analysis in
      relation to inventory, distribution, realization and functional use of
      intonational elements. RESULT: Findings revealed that the unscripted speaking
      styles provided a more comprehensive picture of the inventory and distribution of
      intonation contours, whereas differences in the functional use were more
      prominently reflected in the scripted data sets, in particular the short
      sentences. CONCLUSION: The findings highlight that the type of speaking style
      influences how intonation patterns are realized in disordered as well as healthy
      speech. A combination of scripted as well as unscripted data is, thus, required
      to obtain a comprehensive picture of the intonation abilities of a speaker with
      foreign accent syndrome.

PMID- 25764121
TI  - Investigating the biology of alpha herpesviruses with MS-based proteomics.
AB  - Viruses are intracellular parasites that can only replicate and spread in cells
      of susceptible hosts. Alpha herpesviruses (alpha-HVs) contain double-stranded DNA
      genomes of at least 120 kb, encoding for 70 or more genes. The viral genome is
      contained in an icosahedral capsid that is surrounded by a proteinaceous tegument
      layer and a lipid envelope. Infection starts in epithelial cells and spreads to
      the peripheral nervous system. In the natural host, alpha-HVs establish a chronic
      latent infection that can be reactivated and rarely spread to the CNS. In the
      nonnatural host, viral infection will in most cases spread to the CNS with often
      fatal outcome. The host response plays a crucial role in the outcome of viral
      infection. alpha-HVs do not encode all the genes required for viral replication
      and spread. They need a variety of host gene products including RNA polymerase,
      ribosomes, dynein, and kinesin. As a result, the infected cell is dramatically
      different from the uninfected cell revealing a complex and dynamic interplay of
      viral and host components required to complete the virus life cycle. In this
      review, we describe the pivotal contribution of MS-based proteomics studies over
      the past 15 years to understand the complicated life cycle and pathogenesis of
      four alpha-HV species from the alphaherpesvirinae subfamily: Herpes simplex virus
      1, varicella zoster virus, pseudorabies virus and bovine herpes virus-1. We
      describe the viral proteome dynamics during host infection and the host proteomic
      response to counteract such pathogens. 

PMID- 25764123
TI  - An 80-year-old man with a right upper lobe opacity.
AB  - BACKGROUND AND AIMS: The differential diagnosis of a right upper lobe pulmonary
      opacity in an elderly afebrile patient includes infectious and malignant
      etiology. However, unilateral lung edema should also be included in the
      differential diagnosis. METHODS: Case report of an 80-year-old afebrile patient
      who presented with cough, dyspnea and blood-tinged sputum and had an isolated
      right upper lobe infiltrate on chest X-ray on whom a diagnostic work-up including
      computed tomography scan of the chest and echocardiography was performed.
      RESULTS: Bilateral alveolar opacities and pleural effusions, not apparent on the
      chest X-ray, and a flail posterior leaflet with severe mitral valve regurgitation
      were revealed. His symptoms and findings responded to diuretic treatment.
      CONCLUSION: Pulmonary edema should be considered in a patient with mitral valve
      regurgitation presenting with a unilateral lung infiltrate. Chest computed
      tomography scan findings consistent with heart failure and echocardiography
      demonstrating mitral valve regurgitation are the main clues to the diagnosis.
      Diuretic therapy should cause a rapid improvement of the radiologic and clinical
      findings.

PMID- 25764125
TI  - Polymerase chain reaction-based national surveillance programme to determine the
      distribution and prevalence of Taylorella equigenitalis in South African horses.
AB  - REASONS FOR PERFORMING STUDY: The response to the first outbreak of contagious
      equine metritis in South Africa included pioneering a web-based platform to
      coordinate key aspects of a national, real-time polymerase chain reaction (qPCR)
      based stallion screening programme to determine the distribution and prevalence
      of Taylorella equigenitalis in stallions and exposed mares. OBJECTIVES: To define
      the hypothesised pre-existing status of T. equigenitalis in the South African
      equine population and progression of the epidemiological investigation via the
      implementation of a molecular diagnostic-based surveillance programme. STUDY
      DESIGN: Retrospective case series. METHODS: Screening for T. equigenitalis was
      via a qPCR assay on genital swabs obtained from predilection sites in stallions
      and mares with subsequent confirmation using bacterial culture according to
      prescribed methods. RESULTS: The initial outbreak investigation identified 4
      horses including the index stallion and mare. Traceback of in-contact horses
      identified 26 horses, including a subpopulation focus at the South African
      Lipizzaner Centre where 24/33 resident stallions tested positive for T.
      equigenitalis on qPCR. The national screening programme identified an additional
      9 stallions. A total of 39 horses (36 stallions and 3 mares) tested positive for
      T. equigenitalis by qPCR and T. equigenitalis was isolated from 23 of these
      stallions and 2 of these mares. In addition to the index property, an artificial
      breeding centre where the index case was first identified, an additional 12
      properties with infected horses were identified in 3/9 provinces. Horses on 11 of
      these 12 properties were directly linked to the index property. Two incidents of
      T. equigenitalis transmission associated with artificial insemination were
      recorded. CONCLUSIONS: T. equigenitalis was present in a subpopulation focus
      within the South African horse population prior to the outbreak identification in
      April 2011. Horizontal fomite-associated spread was the most probable route of
      transmission between stallions. The targeted surveillance of stallions and
      exposed mares using a qPCR-based screening programme expedited investigation of
      the distribution and prevalence of T. equigenitalis infection in South African
      horses. The application of qPCR provided a sensitive and practical screening test
      for identification of T. equigenitalis-positive animals as part of an emergency
      response to the first identified cases of T. equigenitalis infection in South
      African horses.

PMID- 25764124
TI  - Cellular Reprogramming Allows Generation of Autologous Hematopoietic Progenitors
      From AML Patients That Are Devoid of Patient-Specific Genomic Aberrations.
AB  - Current treatments that use hematopoietic progenitor cell (HPC) transplantation
      in acute myeloid leukemia (AML) patients substantially reduce the risk of
      relapse, but are limited by the availability of immune compatible healthy HPCs.
      Although cellular reprogramming has the potential to provide a novel autologous
      source of HPCs for transplantation, the applicability of this technology toward
      the derivation of healthy autologous hematopoietic cells devoid of patient
      specific leukemic aberrations from AML patients must first be evaluated. Here, we
      report the generation of human AML patient-specific hematopoietic progenitors
      that are capable of normal in vitro differentiation to myeloid lineages and are
      devoid of leukemia-associated aberration found in matched patient bone marrow.
      Skin fibroblasts were obtained from AML patients whose leukemic cells possessed a
      distinct, leukemia-associated aberration, and used to create AML patient-specific
      induced pluripotent stem cells (iPSCs). Through hematopoietic differentiation of
      AML patient iPSCs, coupled with cytogenetic interrogation, we reveal that AML
      patient-specific HPCs possess normal progenitor capacity and are devoid of
      leukemia-associated mutations. Importantly, in rare patient skin samples that
      give rise to mosaic fibroblast cultures that continue to carry leukemia
      associated mutations; healthy hematopoietic progenitors can also be generated via
      reprogramming selection. Our findings provide the proof of principle that
      cellular reprogramming can be applied on a personalized basis to generate healthy
      HPCs from AML patients, and should further motivate advances toward creating
      transplantable hematopoietic stem cells for autologous AML therapy.

PMID- 25764127
TI  - Outcomes of colonoscopic polypectomy for malignant adenomas: a prospective 30
      year cohort study from a single center (STROBE 1a).
AB  - INTRODUCTION: Surgery is recommended following endoscopic polypectomy for
      malignant adenoma (MA) in the large bowel in patients with risk factors for tumor
      recurrence or distant metastasis are present. OBJECTIVES: We present long-term
      outcomes of a prospective study in patients with endoscopically removed MAs.
      PATIENTS AND METHODS: A total of 128 patients who underwent endoscopic
      polypectomy were followed up for a median of 70.4 months. The criteria for
      adequate polypectomy included endoscopically and histologically (margin >=2 mm)
      complete excision, lack of angioinvasion, and good tumor differentiation (G1 or
      G2). Sixty-seven patients did not meet 1 or more of the criteria (high-risk
      group) and 61 met all of the criteria (low-risk group). Unfavorable outcomes were
      residual disease, lymph node metastasis, recurrent disease, distant metastasis,
      or death due to colorectal cancer. Histological samples from 85 patients were
      reassessed to determine the effect of a margin width of 1 mm or more and tumor
      budding on the outcomes. RESULTS: Surgery was performed in 36 patients (28.1%),
      of whom 32 (47.7%) were high-risk and 4 (6.5%) were low-risk. Unfavorable outcome
      was observed in 10 patients (7.8%; all high-risk; 10 of 67 patients, 14.9%).
      Favorable outcome was observed in 61 of 128 patients who had a 2-mm free margin,
      and in 44 of 85 patients who fulfilled the modified criterion of 1-mm free
      margin. Tumor budding was detected in 17 of 85 patients (20.9%). Unfavorable
      outcome was observed in 2 of these patients (11.7%) and in 5 patients (7.3%)
      without tumor budding (P >0.05). DISCUSSION: Long-term outcomes of an endoscopic
      resection of MAs are good. Bowel resection does not prevent unfavorable outcomes,
      while a reduction of the tumor-free margin would not deteriorate the results
      (STROBE 1B).

PMID- 25764126
TI  - Functions of MiRNA-128 on the regulation of head and neck squamous cell carcinoma
      growth and apoptosis.
AB  - BACKGROUND: Incidence of head and neck squamous cell carcinoma (HNSCC) has
      continuously increased in past years while its survival rate has not been
      significantly improved. There is a critical need to better understand the genetic
      regulation of HNSCC tumorigenesis and progression. In this study, we
      comprehensively analyzed the function of miRNA-128 (miR-128) in the regulation of
      HNSCC growth and its putative targets in vitro and in vivo systems. METHODS: The
      function and targets of miR-128 were investigated in human HNSCC cell lines (JHU
      13 and JHU-22), which were stably transfected with the miR-128 gene using a
      lentiviral delivery system. The expression levels of miR-128 and its targeted
      proteins were analyzed with qRT-PCR, Western blotting and flow cytometry. The
      binding capacity of miRNA-128 to its putative targets was determined using a
      luciferase report assay. MTT, colony formation, and a tumor xenograft model
      further evaluated the effects of miR-128 on HNSCC growth. RESULTS: We generated
      two miR-128 stably transfected human HNSCC cell lines (JHU-13miR-128 and JHU
      22miR-128). Enforced expression of miR-128 was detected in both cultured JHU
      13miR-128 and JHU-22miR-128 cell lines, approximately seventeen to twenty folds
      higher than in vector control cell lines. miRNA-128 was able to bind with the 3'
      untranslated regions of BMI-1, BAG-2, BAX, H3f3b, and Paip2 mRNAs, resulting in
      significant reduction of the targeted protein levels. We found that upregulated
      miR-128 expression significantly inhibited both JHU-13miR-128 and JHU-22miR-128
      cell viability approximately 20 to 40%, and the JHU-22miR-128 tumor xenograft
      growth compared to the vector control groups. CONCLUSIONS: miR-128 acted as a
      tumor suppressor inhibiting the HNSCC growth by directly mediating the expression
      of putative targets. Our results provide a better understanding of miRNA-128
      function and its potential targets, which may be valuable for developing novel
      diagnostic markers and targeted therapy.

PMID- 25764128
TI  - Characterization of amide-alkanediol intermolecular interactions.
AB  - The properties of formamide + 1,2-alkanediol binary liquid systems were studied
      both at the macro- and microscopic levels using a combined experimental and
      computational methodology. Physicochemical properties, infrared spectroscopy, and
      solvatochromic studies together with classic molecular dynamics and quantum
      chemistry calculations allowed the main characteristics of these binary fluids to
      be inferred with regard to the variations of hydrogen bonding with formamide and
      1,2-alkanediol molecular structures, mixture composition, and temperature. The
      complexity of these liquid systems arising from the presence of three different
      functional groups, which may act as hydrogen bond donors and acceptors, is
      analyzed, allowing a detailed picture to be inferred of the studied systems which
      is of relevance both for basic liquid state theory and for industrial purposes. 

PMID- 25764129
TI  - [We need a new profession of psychotherapists - pro].

PMID- 25764130
TI  - [We need a new profession of psychotherapists - contra].

PMID- 25764132
TI  - [The role of colloids in intensive care medicine. Evidence instead of emotions].
AB  - BACKGROUND: Besides albumin, which is gained from human donors, synthetic
      colloids have been playing a dominant role in treating patients in shock and are
      standard therapy in intensive care units (ICU). Since the publication of large
      randomized controlled trials indicating negative effects on renal function, their
      use has been questioned, especially for hydroxyethyl starch products. The
      preliminary assumption that these side effects are only existent in first or
      secondary generation starch fluids was proven incorrect. In fact, the use of
      hydroxyethyl starch products in critically ill patients is prohibited by the
      European Medicines Agency. CURRENT DISCUSSION AND INDICATIONS: Several
      methodological limitations exist in each of these trials that limit the evidence
      value of these investigations, although they served as the basis for the negative
      judgment of the European Medicines Agency. In addition, a large randomized
      controlled trial on the efficacy of gelatin is lacking. The use of colloids in
      ICU patients is indicated in cases where crystalloid volume therapy is
      inadequate. CONCLUSION: Especially during the first 6 h of sepsis, when
      aggressive volume therapy is decisive for patient outcome, colloids may be
      relevant to increase patient survival. The latest guideline on treatment with
      colloids has been published in the German S3 guideline "Intravascular volume
      therapy in adults."

PMID- 25764133
TI  - Accumulation of squalene in a microalga Chlamydomonas reinhardtii by genetic
      modification of squalene synthase and squalene epoxidase genes.
AB  - Several microalgae accumulate high levels of squalene, and as such provide a
      potentially valuable source of this useful compound. However, the molecular
      mechanism of squalene biosynthesis in microalgae is still largely unknown. We
      obtained the sequences of two enzymes involved in squalene synthesis and
      metabolism, squalene synthase (CrSQS) and squalene epoxidase (CrSQE), from the
      model green alga Chlamydomonas reinhardtii. CrSQS was functionally characterized
      by expression in Escherichia coli and CrSQE by complementation of a budding yeast
      erg1 mutant. Transient expression of CrSQS and CrSQE fused with fluorescent
      proteins in onion epidermal tissue suggested that both proteins were co-localized
      in the endoplasmic reticulum. CrSQS-overexpression increased the rate of
      conversion of 14C-labeled farnesylpyrophosphate into squalene but did not lead to
      over-accumulation of squalene. Addition of terbinafine caused the accumulation of
      squalene and suppression of cell survival. On the other hand, in CrSQE-knockdown
      lines, the expression level of CrSQE was reduced by 59-76% of that in wild-type
      cells, and significant levels of squalene (0.9-1.1 MUg mg-1 cell dry weight)
      accumulated without any growth inhibition. In co-transformation lines with CrSQS
      overexpression and CrSQE-knockdown, the level of squalene was not increased
      significantly compared with that in solitary CrSQE-knockdown lines. These results
      indicated that partial knockdown of CrSQE is an effective strategy to increase
      squalene production in C. reinhardtii cells. 

PMID- 25764134
TI  - Resolving the daratumumab interference with blood compatibility testing.
AB  - BACKGROUND: Daratumumab (DARA), a promising novel therapy for multiple myeloma,
      is an IgG1kappa monoclonal antibody that recognizes CD38 on myeloma cells. During
      routine compatibility testing, we observed that the plasma of five of five DARA
      treated patients demonstrated a positive antibody screen and panreactivity on red
      blood cell (RBC) panel testing. We hypothesized that the observed panreactivity
      reflected DARA binding to CD38 on reagent RBCs, and we investigated methods to
      prevent this binding. STUDY DESIGN AND METHODS: DARA binding to CD38+ or CD38-
      HL60 cells was assessed by flow cytometry. To remove cell surface CD38, cells
      were incubated with dithiothreitol (DTT) or trypsin. Soluble CD38 or anti-DARA
      was used to neutralize DARA in solution. Routine blood bank serologic methods
      were used to test samples from DARA-treated patients and normal plasma samples
      spiked with DARA and/or alloantibodies. RESULTS: Normal plasma samples spiked
      with DARA (0.1-10 ug/mL) and incubated with reagent RBCs recapitulated the
      interference observed with samples from DARA-treated patients. Flow cytometry
      experiments confirmed DARA binding to CD38+ HL60 cells, but not to CD38-
      controls. DTT treatment of CD38+ HL60 cells reduced DARA binding by 92% by
      denaturing cell surface CD38. Treating DARA-containing plasma with soluble CD38
      or anti-DARA idiotype also inhibited DARA binding. CONCLUSION: DARA causes
      panreactivity in vitro by binding to CD38 on reagent RBCs. Treating reagent RBCs
      with DTT is a robust method to negate the DARA interference, enabling the safe
      provision of blood to DARA-treated patients. Because DTT denatures Kell antigens,
      K- units are provided to these patients.

PMID- 25764135
TI  - Alpha-catenin-dependent recruitment of the centrosomal protein CAP350 to adherens
      junctions allows epithelial cells to acquire a columnar shape.
AB  - Epithelial morphogenesis involves a dramatic reorganisation of the microtubule
      cytoskeleton. How this complex process is controlled at the molecular level is
      still largely unknown. Here, we report that the centrosomal microtubule (MT)
      binding protein CAP350 localises at adherens junctions in epithelial cells. By
      two-hybrid screening, we identified a direct interaction of CAP350 with the
      adhesion protein alpha-catenin that was further confirmed by co
      immunoprecipitation experiments. Block of epithelial cadherin (E-cadherin)
      mediated cell-cell adhesion or alpha-catenin depletion prevented CAP350
      localisation at cell-cell junctions. Knocking down junction-located CAP350
      inhibited the establishment of an apico-basal array of microtubules and impaired
      the acquisition of columnar shape in Madin-Darby canine kidney II (MDCKII) cells
      grown as polarised epithelia. Furthermore, MDCKII cystogenesis was also defective
      in junctional CAP350-depleted cells. CAP350-depleted MDCKII cysts were smaller
      and contained either multiple lumens or no lumen. Membrane polarity was not
      affected, but cortical microtubule bundles did not properly form. Our results
      indicate that CAP350 may act as an adaptor between adherens junctions and
      microtubules, thus regulating epithelial differentiation and contributing to the
      definition of cell architecture. We also uncover a central role of alpha-catenin
      in global cytoskeleton remodelling, in which it acts not only on actin but also
      on MT reorganisation during epithelial morphogenesis. 

PMID- 25764138
TI  - Estimating prevalence of overweight or obese children and adolescents in small
      geographic areas using publicly available data.
AB  - INTRODUCTION: Interventions for pediatric obesity can be geographically targeted
      if high-risk populations can be identified. We developed an approach to estimate
      the percentage of overweight or obese children aged 2 to 17 years in small
      geographic areas using publicly available data. We piloted our approach for
      Georgia. METHODS: We created a logistic regression model to estimate the
      individual probability of high body mass index (BMI), given data on the
      characteristics of the survey participants. We combined the regression model with
      a simulation to sample subpopulations and obtain prevalence estimates. The models
      used information from the 2001-2010 National Health and Nutrition Examination
      Survey, the 2010 Census, and the 2010 American Community Survey. We validated our
      results by comparing 1) estimates for adults in Georgia produced by using our
      approach with estimates from the Centers for Disease Control and Prevention (CDC)
      and 2) estimates for children in Arkansas produced by using our approach with
      school examination data. We generated prevalence estimates for census tracts in
      Georgia and prioritized areas for interventions. RESULTS: In DeKalb County, the
      mean prevalence among census tracts varied from 27% to 40%. For adults, the
      median difference between our estimates and CDC estimates was 1.3 percentage
      points; for Arkansas children, the median difference between our estimates and
      examination-based estimates data was 1.7 percentage points. CONCLUSION:
      Prevalence estimates for census tracts can be different from estimates for the
      county, so small-area estimates are crucial for designing effective
      interventions. Our approach validates well against external data, and it can be a
      relevant aid for planning local interventions for children.

PMID- 25764139
TI  - Reach of Supplemental Nutrition Assistance Program-Education (SNAP-Ed)
      interventions and nutrition and physical activity-related outcomes, California,
      2011-2012.
AB  - INTRODUCTION: This study combined information on the interventions of the US
      Department of Agriculture's Supplemental Nutrition Assistance Program-Education
      with 5,927 interview responses from the California Health Interview Survey to
      investigate associations between levels of intervention reach in low-income
      census tracts in California and self-reported physical activity and consumption
      of fruits and vegetables, fast food, and sugar-sweetened beverages. METHODS: We
      determined 4 levels of intervention reach (low reach, moderate reach, high reach,
      and no intervention) across 1,273 program-eligible census tracts from data on
      actual and eligible number of intervention participants. The locations of
      California Health Interview Survey respondents were geocoded and linked with
      program data. Regression analyses included measures for sex, age, race/ethnicity,
      and education. RESULTS: Adults and children from high-reach census tracts
      reported eating more fruits and vegetables than adults and children from no
      intervention census tracts. Adults from census tracts with low, moderate, or high
      levels of reach reported eating fast food less often than adults from no
      intervention census tracts. Teenagers from low-reach census tracts reported more
      physical activity than teenagers in no-intervention census tracts. CONCLUSION:
      The greatest concentration of Supplemental Nutrition Assistance Program-Education
      interventions was associated with adults and children eating more fruits and
      vegetables and adults eating fast food less frequently. These findings
      demonstrate the potential impact of such interventions as implemented by numerous
      organizations with diverse populations; these interventions can play an important
      role in addressing the obesity epidemic in the United States. Limitations of this
      study include the absence of measures of exposure to the intervention at the
      individual level and low statistical power for the teenager sample.

PMID- 25764137
TI  - Influence of physical education on moderate-to-vigorous physical activity of
      urban public school children in St. Louis, Missouri, 2011-2014.
AB  - We quantified the moderate-to-vigorous physical activity (MVPA, heart rate >=140
      bpm) of urban public elementary school children on school days with and
      schooldays without physical education (PE) class by using continuous heart rate
      monitoring. The heart rate of 81 students (93.8% black) in grades 3 and 5 was
      recorded in 15-second intervals. On the basis of 575 school-day observations
      (mean 7.1 days/student), students accumulated 44.4 (standard deviation [SD],
      34.4) minutes of MVPA on days with PE and 30.6 (SD, 29.9) MVPA minutes on days
      without PE (P < .001). School policies should promote daily PE to help children
      in under-resourced areas achieve the recommended 60 minutes per day of MVPA.

PMID- 25764140
TI  - Improving heart healthy lifestyles among participants in a Salud para su Corazon
      promotores model: the Mexican pilot study, 2009-2012.
AB  - INTRODUCTION: In Mexico, cardiovascular disease and its risk factors are growing
      problems and major public health concerns. The objective of this study was to
      implement cardiovascular health promotion and disease prevention activities of
      the Salud para su Corazon model in a high-risk, impoverished, urban community in
      Mexico City. METHODS: We used a pretest-posttest (baseline to 12-week follow-up)
      design without a control group. Material from Salud para su Corazon was validated
      and delivered by promotores (community health workers) to community members from
      6 geographic areas. Two validated, self-administered questionnaires that assessed
      participants' knowledge and behaviors relating to heart health were administered.
      We used t tests and chi(2) tests to evaluate pretest and posttest differences, by
      age group (<=60 and >60 years), for participants' 3 heart-healthy habits, 3 types
      of physical activity, performance skills, and anthropometric and clinical
      measurements. RESULTS: A total of 452 (82%) adult participants completed the
      program. Heart-healthy habits from pretest to posttest varied by age group.
      "Taking action" to modify lifestyle behaviors increased among adults aged 60 or
      younger from 31.5% to 63.0% (P < .001) and among adults older than 60 from 30.0%
      to 45.0% (P < .001). Positive responses for cholesterol and fat consumption
      reduction were seen among participants 60 or younger (P = .03). Among those older
      than 60, salt reduction and weight control increased (P = .008). Mean blood
      glucose concentration among adults older than 60 decreased postintervention (P =
      .03). CONCLUSION: Significant improvements in some heart-healthy habits were seen
      among adult participants. The model has potential to improve heart-healthy habits
      and facilitate behavioral change among high-risk adults.

PMID- 25764141
TI  - Methane concentrations in water wells unrelated to proximity to existing oil and
      gas wells in northeastern Pennsylvania.
AB  - Recent studies in northeastern Pennsylvania report higher concentrations of
      dissolved methane in domestic water wells associated with proximity to nearby gas
      producing wells [ Osborn et al. Proc. Natl. Acad. Sci. U. S. A. 2011 , 108 , 8172
      ] and [ Jackson et al. Proc. Natl. Acad. Sci. U. S. A. , 2013 , 110 , 11250 ]. We
      test this possible association by using Chesapeake Energy's baseline data set of
      over 11,300 dissolved methane analyses from domestic water wells, densely arrayed
      in Bradford and nearby counties (Pennsylvania), and near 661 pre-existing oil and
      gas wells. The majority of these, 92%, were unconventional wells, drilled with
      horizontal legs and hydraulically fractured. Our data set is hundreds of times
      larger than data sets used in prior studies. In contrast to prior findings, we
      found no statistically significant relationship between dissolved methane
      concentrations in groundwater from domestic water wells and proximity to pre
      existing oil or gas wells. Previous analyses used small sample sets compared to
      the population of domestic wells available, which may explain the difference in
      prior findings compared to ours. 

PMID- 25764142
TI  - Women in print-reply.

PMID- 25764144
TI  - Total synthesis of sinenside A.
AB  - The first total synthesis of norlignan glucoside sinenside A has been
      accomplished. An intramolecular acetalization reaction has been employed as the
      key skeletal construct to forge the central cyclic disaccharide core. The trans
      1,2-diol configuration present in the cyclic disaccharide of this natural product
      is unique and has been addressed by setting this configuration at the beginning.
      A 1,2-orthoester group has been selected as a handle for both sp glycosidation
      and for differentiation of the C2'-OH (that participates in the key acetalization
      reaction) of the sugar unit. 

PMID- 25764145
TI  - Autochthonous Hookworm-Related Cutaneous Larva Migrans Disease in Northeastern
      Italy: A Case Report.
AB  - Here we report the case of a 42-yr-old patient who presented himself to us with a
      serpiginous erythematous lesion from the wrist of the right forearm up the arm to
      the right shoulder A similar lesion of a smaller size was also present in the
      left forearm. On the basis of clinical manifestations and progression of the
      lesion, combined with previous treatments and different diagnostic
      investigations, hookworm-related cutaneous larva migrans (HrCLM) disease was
      hypothesized. Albendazole was employed as treatment and the resolution of the
      symptoms confirmed the diagnosis. The relevance of the reported case relies on 3
      main aspects: the acquisition of the disease in Italy, the initial treatment with
      topical corticosteroids that sped up the progression of the cutaneous trail, and
      the uncommon location of the lesions. Furthermore, the anamnestic data and the
      laboratory/clinical investigations strongly suggested an occupational exposure to
      the etiological agent. As illustrated here, HrCLM might represent a challenge for
      Western physicians in terms of diagnosis, treatment, and ways of acquisition.
      Describing the clinical presentation and the treatment of cases of cutaneous
      larva migrans might contribute to early and correct diagnosis, to an increase of
      our knowledge on this disease, and to an update on its epidemiology. 

PMID- 25764146
TI  - Molecular Survey of Hepatozoon canis in Red Foxes (Vulpes vulpes) from Romania.
AB  - Blood samples of 119 red foxes, originating from 44 hunting grounds of 3 western
      counties (Arad, Hunedoara, and Timis) of Romania, have been examined for the
      presence of Hepatozoon canis infection using the conventional polymerase chain
      reaction (PCR) of the fragment of 18S rRNA gene. Overall, 15 (12.6%) samples were
      found to be PCR-positive. Of the sampled hunting grounds, 29.5% (13/44) were
      found positive. Positive samples were recorded in all screened counties with the
      prevalence of 14.8% (9/61) in Arad, 9.8% (5/51) in Timis, and 14.3% (1/7) in
      Hunedoara, respectively. No correlation was found (P > 0.05) between H. canis
      positivity and gender or territorial distribution of the infection. To confirm
      PCR results, 9 randomly selected amplicons were sequenced. The obtained sequences
      were identical to each other, confirmed the results of the conventional PCR, and
      showed 98-100% homology to other H. canis sequences. The results of the current
      survey support the role of red foxes as sylvatic reservoirs of H. canis in
      Romania. 

PMID- 25764143
TI  - T2* relaxometry and volume predict semi-quantitative histological scoring of an
      ACL bridge-enhanced primary repair in a porcine model.
AB  - Magnetic resonance imaging (MRI) variables, such as T2* and volume, can predict
      the healing ligament structural properties. How these MR variables relate to semi
      quantitative histology of the healing ACL is yet unknown. We hypothesized that
      T2* and volume would predict the histological scoring of a healing ACL. Yucatan
      minipigs underwent ACL transection and received bridge-enhanced ACL repair or no
      treatment. The surgical legs were harvested after 52 weeks and imaged using a
      high resolution 2-echo sequence. For each ligament, the volume and median T2*
      values were determined. The ACL specimens were then histologically analyzed using
      the advanced Ligament Maturity Index (LMI). The T2* of the healing ligaments
      significantly predicted the total LMI score as well as the cell, collagen and
      vessel sub-scores; R(2)  = 0.78, 0.67, 0.65, and 0.60, respectively (p <= 0.001).
      The ligament volume also predicted the total LMI score, cell, and collagen sub
      scores; R(2)  = 0.39, 0.33, 0.37, and 0.60, respectively (p <= 0.001). A lower
      ligament T2* or a higher volume was associated with higher histological scores of
      the healing ligaments. This study provides a critical step in the development of
      a non-invasive method to evaluate ligament healing on a microscopic scale.

PMID- 25764147
TI  - Locum tenens and telepsychiatry: trends in psychiatric care.
AB  - BACKGROUND: There is a national shortage of psychiatrists, and according to
      nationally available data, it is projected to get worse. Locum tenens psychiatry
      and telepsychiatry are two ways to fill the shortages of psychiatric providers
      that exist in many areas in the United States. Employment and salary data in
      these areas can be used to illuminate current trends and anticipate future
      solutions to the problem of increasing demand for, and decreasing supply of,
      psychiatrists in the United States. MATERIALS AND METHODS: A search was conducted
      of the literature and relevant Web sites, including PubMed, Google Scholar, and
      www.google.com , as well as information obtained from locum tenens and
      telepsychiatry organizations. RESULTS: There is a dearth of data on the use of
      locum tenens in the field of psychiatry, with little available prior to 2000 and
      few published studies since then. The majority of the data available are survey
      data from commercial entities. These data show trends toward increasing demand
      for psychiatry along with increasing salaries and indicate the utilization of
      telepsychiatry and locum tenens telepsychiatry is increasing. The published
      academic data that are available show that although locum tenens psychiatry is
      slightly inferior to routine psychiatric care, telepsychiatry is generally
      equivalent to face-to-face care. CONCLUSIONS: One can anticipate that as the
      national shortage of psychiatrists is expected to accelerate, use of both locum
      tenens and telepsychiatry may also continue to increase. Telepsychiatry offers
      several possible advantages, including lower cost, longer-term services, quality
      of care, and models that can extend psychiatric services. If current trends
      continue, systems that demand face-to-face psychiatry may find themselves paying
      higher fees for locum tenens psychiatrists, whereas others may employ
      psychiatrists more efficiently with telepsychiatry.

PMID- 25764148
TI  - Deferasirox chelation therapy in patients with transfusion-dependent MDS: a 'real
      world' report from two regional Italian registries: Gruppo Romano Mielodisplasie
      and Registro Basilicata.
AB  - Deferasirox (DFX) is an orally administered iron chelator approved for use in
      patients with transfusion-dependent iron overload due to myelodysplastic
      syndromes (MDS). The safety and efficacy of DFX has been explored in clinical
      trial settings, but there is little data on unselected patients with MDS. The aim
      of this study was to retrospectively evaluate the safety, compliance, efficacy
      and effect on haematopoiesis of DFX in a large 'real-world' MDS population. One
      hundred and eighteen patients with transfusion-dependent MDS were treated with
      DFX across 11 centres in Italy. Serum ferritin levels, haematological response,
      dosing, adverse events and transfusion dependence were recorded at baseline, 3,
      6, 12 and 24 months following initiation of treatment. DFX reduced mean serum
      ferritin levels from 1790 to 1140 ng/mL (P < 0.001), with 7.1% of patients
      achieving transfusion independence. Significant haematological improvement was
      seen in erythroid (17.6%), platelet (5.9%) and neutrophil counts (7.1%). Adverse
      events were reported in 47.5% of patients, including gastrointestinal and renal
      toxicity. Regression analysis showed that higher starting doses of DFX are
      associated with transfusion independence at 24 months. DFX is a safe, effective
      treatment for transfusion-dependent MDS that can lead to transfusion independence
      and haematological improvement in a subset of patients.

PMID- 25764149
TI  - Effect of Fermented Red Ginseng Extract Enriched in Ginsenoside Rg3 on the
      Differentiation and Mineralization of Preosteoblastic MC3T3-E1 Cells.
AB  - In this study, red ginseng extract (RGE) was converted into high-content minor
      ginsenosides by fermenting with Bgp1 enzymes at 37 degrees C for 5 days. Compared
      to the RGE, the minor ginsenoside contents were increased in fermented red
      ginseng extract (FRGE). Moreover, the amount of minor ginsenosides such as Rh1
      (11%) and Rg2 (16%) was slightly augmented, while the level of Rg3 (33%) was
      significantly increased after bioconversion. Furthermore, we also examined and
      compared the effect of RGE and FRGE on the differentiation and mineralization of
      preosteoblastic MC3T3-E1 cells. Similarly, the level of mRNA expression of
      intracellular alkaline phosphatase (ALP) activity, type-1 collagen (Col-I) was
      also increased. Based on the comparison, it is clear that the FRGE has improved
      effects on bone formation and differentiation of preosteoblastic MC3T3-E1 cells. 

PMID- 25764150
TI  - Evaluating the bioequivalence of clopidogrel generic formulations.

PMID- 25764151
TI  - Afrezza: An inhaled approach to insulin delivery.
AB  - PURPOSE: The purpose of this article is to educate nurse practitioners about
      Afrezza. DATA SOURCES: A comprehensive literature search was conducted using
      MEDLINE for clinical trial data. Information from the Centers of Disease Control
      and Prevention, World Health Organization, clinical guidelines, Food and Drug
      Administration labeling, briefings, and press releases was also utilized.
      CONCLUSIONS: Afrezza represents a promising noninjectable insulin delivery option
      for type 1 and type 2 diabetes mellitus. According to clinical trial evidence, it
      appears to be efficacious and comparable to currently available prandial insulin
      options, and based on current data, it appears to be a safe alternative to
      injectable insulin with high treatment satisfaction. IMPLICATIONS FOR PRACTICE:
      Afrezza may offer an alternative for insulin naive patients who are hesitant
      about initiating traditional insulin. It may cause less weight gain when compared
      to subcutaneous mealtime insulin with a more rapid absorption and elimination
      profile, but more long-term studies are needed. Afrezza is limited in type 1
      diabetes to use in combination with basal insulin. It is not recommended in the
      treatment of diabetic ketoacidosis or for patients who smoke. It is
      contraindicated during hypoglycemic episodes, in chronic lung diseases, or in
      those with hypersensitivity to regular human insulin or any of the excipients in
      Afrezza.

PMID- 25764153
TI  - Differences between Current and Past Self-Injurers: How and Why Do People Stop?
AB  - This research sought to clarify how some self-injurers cease the behavior,
      maintaining this for at least 1 year. Using the Experiential Avoidance Model
      (EAM), we examined whether characteristics of self-injurers remain in people who
      have successfully ceased self-injury and what, by implication, might be targeted
      to improve therapeutic efficacy. The study was conducted using an online cross
      sectional survey of 215 first-year university students. Past self-injurers (34)
      scored significantly better on subscales of the General Health Questionnaire, as
      well as Distress Tolerance, Experiential Avoidance, and Self-blame compared to
      Current self-injurers (29). The Experiential Avoidance Model is a useful basis
      for understanding self-injury, and informing therapeutic approaches. Reducing
      Anxiety, and developing Tolerance and Positive Emotional Intensity may be keys to
      ceasing self-injury. 

PMID- 25764152
TI  - The Ilizarov method for the treatment of complex tibial fractures and non-unions
      in a mass casualty setting: the 2005 earthquake in Pakistan.
AB  - We report our experience in treating victims of the recent earthquake disaster in
      Pakistan. Our experience was based on two humanitarian missions to Islamabad: one
      in October 2005, 10 days after the earthquake, and the second in January 2006.
      The mission consisted of a team of orthopaedic surgeons and a second team of
      plastic surgeons. The orthopaedic team bought all the equipment for application
      of Ilizarov external fixators. We treated patients who had already received basic
      treatment in the region of the disaster and subsequently had been evacuated to
      Islamabad. During the first visit, we treated 12 injured limbs in 11 patients.
      Four of these patients were children. All cases consisted of complex
      multifragmentary fractures associated with severe crush injuries. All fractures
      involved the tibia, which were treated with Ilizarov external fixators. Nine
      fractures were type 3b open injuries. Eight were infected requiring debridement
      of infected bone and acute shortening. During a second visit, we reviewed all
      patients treated during our first mission. In addition, we treated 13 new
      patients with complex non-unions. Eight of these patients were deemed to be
      infected. All patients had previous treatment with monolateral fixators as well
      as soft tissue coverage procedures, except one patient who had had an IEF applied
      by another team. All these patients had revision surgery with circular frames.
      All patients from both groups were allowed to fully weight-bear post-operatively,
      after a short period of elevation to allow the flaps to take. Overall, all
      fractures united except one case who eventually had an amputation. Four patients
      had a corticotomy and lengthening, and three of them had a successful restoration
      of limb length. The fourth patient was the one with the eventual amputation. 

PMID- 25764154
TI  - Development of a series of near-infrared dark quenchers based on Si-rhodamines
      and their application to fluorescent probes.
AB  - Near-infrared (NIR) fluorescent probes based on the Forster resonance energy
      transfer (FRET) mechanism have various practical advantages, and their molecular
      design is generally based on the use of NIR dark quenchers, which are
      nonfluorescent dyes, as cleavable FRET acceptors. However, few NIR dark quenchers
      can quench fluorescence in the Cy7 region (over 780 nm). Here, we describe Si
      rhodamine-based NIR dark quenchers (SiNQs), which show broad absorption covering
      this region. They are nonfluorescent independently of solvent polarity and pH,
      probably due to free rotation of the bond between the N atom and the xanthene
      moiety. SiNQs can easily be structurally modified to tune their water-solubility
      and absorption spectra, enabling flexible design of appropriate FRET pair for
      various NIR fluorescent dyes. To demonstrate the usefulness of SiNQs, we designed
      and synthesized a NIR fluorescent probe for matrix metalloproteinase (MMP)
      activity using SiNQ780. This probe 1 could detect MMP activity in vitro, in
      cultured cells and in a tumor-bearing mouse, in which the tumor was clearly
      visualized, by NIR fluorescence. We believe SiNQs will be useful for the
      development of a wide range of practical NIR fluorescent probes. 

PMID- 25764155
TI  - Elevated serum adenosine deaminase levels in secondary hemophagocytic
      lymphohistiocytosis.
AB  - INTRODUCTION: Hemophagocytic lymphohistiocytosis (HLH) is a severe
      hyperinflammatory condition caused by activated T cells and macrophages.
      Adenosine deaminase (ADA) plays an important role in immune regulation,
      especially in the proliferation, maturation, and differentiation of lymphocytes.
      Its role has been studied in inflammation and malignancy. Here, we present for
      the first time the alteration of ADA in secondary HLH (sHLH). METHODS: Serum ADA
      levels were measured in 20 cases with lymphoma-associated hemophagocytic syndrome
      (LAHS), 15 with infection-associated hemophagocytic syndrome (IAHS), six with
      macrophage activation syndrome (MAS) as experimental group. Additionally, we
      enrolled 20 cases with lymphoma, 15 with infection, six with autoimmunity who
      were all not associated with HLH as conditional control group and 20 healthy
      subjects as blank group. We also demonstrated the ADA levels in 20 LAHS cases and
      21 benign disease-associated HLH cases (IAHS and MAS). RESULTS: Serum ADA levels
      were significantly higher in patients with LAHS, IAHS, and MAS compared to the
      healthy subjects (P < 0.001) and conditional control group (P < 0.05). Serum ADA
      levels of patients with LAHS were significantly higher than benign disease
      associated HLH cases (P < 0.05). The optimum ADA cutoff point for LAHS was 89.25
      U/L, with a sensitivity and specificity of 85.0% and 76.2%, respectively.
      CONCLUSION: Serum ADA levels were increased in sHLH suggesting a partial role of
      activated T-cell response in the disease pathophysiology. Serum ADA levels were
      particularly higher in LAHS and probably be a potential indicator of underlying
      lymphoma in sHLH patients.

PMID- 25764156
TI  - MiR-25 protects cardiomyocytes against oxidative damage by targeting the
      mitochondrial calcium uniporter.
AB  - MicroRNAs (miRNAs) are a class of small non-coding RNAs, whose expression levels
      vary in different cell types and tissues. Emerging evidence indicates that tissue
      specific and -enriched miRNAs are closely associated with cellular development
      and stress responses in their tissues. MiR-25 has been documented to be abundant
      in cardiomyocytes, but its function in the heart remains unknown. Here, we report
      that miR-25 can protect cardiomyocytes against oxidative damage by down
      regulating mitochondrial calcium uniporter (MCU). MiR-25 was markedly elevated in
      response to oxidative stimulation in cardiomyocytes. Further overexpression of
      miR-25 protected cardiomyocytes against oxidative damage by inactivating the
      mitochondrial apoptosis pathway. MCU was identified as a potential target of miR
      25 by bioinformatical analysis. MCU mRNA level was reversely correlated with miR
      25 under the exposure of H2O2, and MCU protein level was largely decreased by miR
      25 overexpression. The luciferase reporter assay confirmed that miR-25 bound
      directly to the 3' untranslated region (UTR) of MCU mRNA. MiR-25 significantly
      decreased H2O2-induced elevation of mitochondrial Ca2+ concentration, which is
      likely to be the result of decreased activity of MCU. We conclude that miR-25
      targets MCU to protect cardiomyocytes against oxidative damages. This finding
      provides novel insights into the involvement of miRNAs in oxidative stress in
      cardiomyocytes. 

PMID- 25764157
TI  - SOCS3 silencing attenuates eosinophil functions in asthma patients.
AB  - Eosinophils are one of the key inflammatory cells in asthma. Eosinophils can
      exert a wide variety of actions through expression and secretion of multiple
      molecules. Previously, we have demonstrated that eosinophils purified from
      peripheral blood from asthma patients express high levels of suppressor of
      cytokine signaling 3 (SOCS3). In this article, SOCS3 gene silencing in
      eosinophils from asthmatics has been carried out to achieve a better
      understanding of the suppressor function in eosinophils. SOCS3 siRNA treatment
      drastically reduced SOCS3 expression in eosinophils, leading to an inhibition of
      the regulatory transcription factors GATA-3 and FoxP3, also interleukin (IL)-10;
      in turn, an increased STAT3 phosphorilation was observed. Moreover, SOCS3
      abrogation in eosinophils produced impaired migration, adhesion and
      degranulation. Therefore, SOCS3 might be regarded as an important regulator
      implicated in eosinophil mobilization from the bone marrow to the lungs during
      the asthmatic process. 

PMID- 25764158
TI  - A polymorphism at the translation start site of the vitamin D receptor gene is
      associated with the response to anti-osteoporotic therapy in postmenopausal women
      from southern Italy.
AB  - The present study investigated the effect of two single nucleotide polymorphisms
      (SNPs) of the vitamin D receptor (VDR) gene, rs1544410 A/G and rs2228570 C/T, in
      modulating bone mineral density (BMD) and the response to treatment with
      bisphosphonates or strontium ranelate in postmenopausal osteoporosis (PMO). Four
      hundred eighteen postmenopausal women from Southern Italy treated with
      bisphosphonates or strontium ranelate for three years were enrolled and
      stratified according to their genotype. Changes in BMD were expressed as the
      delta t-score (Deltat-score). Allelic frequencies for rs1544410 A/GSNP were 11.2%
      AA, 50.0% GA and 38.8% GG; for rs2228570 C/TSNP were 54.8% CC, 39.5% TC and 5.7%
      TT. TT carriers showed a lower t-score than TC and CC (both p < 0.02) genotypes
      and were more responsive to the therapy when compared to both TC (p < 0.02) and
      CC (p < 0.05) carriers. Specifically, TT carriers receiving alendronate
      demonstrated a significant improvement of the Deltat-score compared to TC and CC
      (both p < 0.0001) carriers. After adjustment for confounders, the Deltat-score
      showed evidence of a statistically significant positive association with TT in
      all treatments considered. Therapy response was independent of rs1544410 A/G SNP;
      instead, rs2228570 C/TSNP was associated with a better response to antiresorptive
      treatment, thus suggesting that the therapy for PMO should be personalized. 

PMID- 25764160
TI  - Helper T lymphocyte response in the peripheral blood of patients with
      intraepithelial neoplasia submitted to immunotherapy with pegylated interferon
      alpha.
AB  - Immunotherapy in cancer patients is a very promising treatment and the
      development of new protocols and the study of the mechanisms of regression is
      imperative. The objective of this study was to evaluate the production of
      cytokines in helper T (CD4+) lymphocytes during immunotherapy with pegylated IFN
      alpha in patients with cervical intraepithelial neoplasia (CIN). We conducted a
      prospective study with 17 patients with CIN II-III using immunotherapy with
      pegylated IFN-alpha subcutaneouly weekly, and using flow cytometry we evaluated
      the peripheric CD4+ T lymphocytes. The results show that in the regression group
      the patients presented a significant increase in the amount of IFN-gamma during
      the entire immunotherapy, compared with the group without a response. The amount
      of CD4+ T lymphocytes positive for IL-2, IL-4, IL-10 and TGF-beta is
      significantly lower in patients with good clinical response. The results also
      demonstrate that patients with regression have a higher amount of intracellular
      TNF-alpha in CD4+ T lymphocytes before the start of treatment. Analyzing these
      data sets, it can be concluded that immunotherapy is a viable clinical treatment
      for patients with high-grade CIN and that the regression is dependent on the
      change in the immune response to a Th1 pattern. 

PMID- 25764161
TI  - Impact of soluble HLA-G levels and endometrial NK cells in uterine flushing
      samples from primary and secondary unexplained infertile women.
AB  - The aim of this research was to determine the levels of human leukocyte antigen G
      (HLA-G) and endometrial Natural Killer ((e)NK) cell percentages in uterine
      flushing samples from primary and secondary infertile women. sHLA-G levels were
      lower in the uterine flushing samples from primary infertile women in comparison
      with women with secondary infertility. Lower CD56+KIR2DL4+ (e)NK cell percentages
      were detected in primary infertile women compared with secondary infertile women.
      This is the first study demonstrating that primary and secondary unexplained
      infertilities are characterized by different basal sHLA-G levels and
      CD56+KIR2DL4+ (e)NK cell percentages. 

PMID- 25764162
TI  - Occurrence of Postictal alpha/beta Activity During Maintenance Course of
      Electroconvulsive Therapy.
AB  - We are aware of a report of postictal alpha activity after seizures in Epilepsy
      and Behavior. We would like to report another case of a similar phenomenon in a
      woman receiving maintenance electroconvulsive therapy. 

PMID- 25764163
TI  - Electroconvulsive therapy and holistic healing.

PMID- 25764164
TI  - Electroconvulsive therapy-induced manic episode for a patient with bipolar
      depression: a case report.

PMID- 25764165
TI  - Trigeminal nerve stimulation for clinical trials in neuropsychiatry: the issue of
      skin integrity.

PMID- 25764159
TI  - Exploring the secrets of long noncoding RNAs.
AB  - High-throughput sequencing has revealed that the majority of RNAs have no
      capacity to encode protein. Among these non-coding transcripts, recent work has
      focused on the roles of long noncoding RNAs (lncRNAs) of >200 nucleotides.
      Although many of their attributes, such as patterns of expression, remain largely
      unknown, lncRNAs have key functions in transcriptional, post-transcriptional, and
      epigenetic gene regulation; Also, new work indicates their functions in
      scaffolding ribonuclear protein complexes. In plants, genome-wide identification
      of lncRNAs has been conducted in several species, including Zea mays, and recent
      research showed that lncRNAs regulate flowering time in the photoperiod pathway,
      and function in nodulation. In this review, we discuss the basic mechanisms by
      which lncRNAs regulate key cellular processes, using the large body of knowledge
      on animal and yeast lncRNAs to illustrate the significance of emerging work on
      lncRNAs in plants. 

PMID- 25764166
TI  - Continuation and maintenance electroconvulsive therapy--a conceptual framework?

PMID- 25764167
TI  - Elevated risks of subsequent endometrial cancer development among breast cancer
      survivors with different hormone receptor status: a SEER analysis.
AB  - Estrogen receptor (ER)-positive breast cancer patients treated with tamoxifen are
      known to have an elevated risk of subsequent endometrial cancer. However, it is
      unclear if ER-negative patients also have a higher risk of endometrial cancer.
      This population-based study aims to evaluate whether breast cancer patients with
      distinctive ER and PR status possess differential risks in developing delayed
      endometrial malignancy. Data were obtained from the Surveillance, Epidemiology,
      and End Results program (1992-2009). Standardized incidence ratio (SIR) was
      calculated as the observed cases of endometrial cancers among breast cancer
      survivors compared with the expected cases in the general population. Data were
      stratified by latency periods, race, age, and calendar year of breast cancer
      diagnosis. We identified 2044 patients who developed a second primary endometrial
      cancer among 289,933 breast cancer survivors. The overall SIRs for subsequent
      endometrial cancers were increased in all of the four subtypes (ER+PR+, ER+PR-,
      ER-PR+, and ER-PR-) of breast cancer. SIR was increased for all latency periods
      except for the initial 6-11 months after breast cancer diagnosis. Stratifying by
      age of diagnosis, elevated SIRs in all ER/PR groups were statistically
      significant among patients diagnosed with breast cancer after the age of 40.
      Demographically, non-Hispanic whites had increased SIRs in all subtypes of breast
      cancer, while Hispanic whites had no statistically elevated SIRs. Here we showed
      that patients with invasive breast cancer have a higher risk of developing
      subsequent endometrial cancer regardless of ER or PR status. The increased risk
      among hormone receptor-negative breast cancer survivors raises concerns whether
      common etiological factors among these breast cancer subtypes increase the
      susceptibility to develop endometrial cancer. Lower threshold for routine
      endometrial cancer surveillance may be warranted.

PMID- 25764169
TI  - Cell-scaffold adhesion dynamics measured in first seconds predicts cell growth on
      days scale - optical tweezers study.
AB  - Understanding the cell-biomaterial interface from the very first contact is of
      crucial importance for their successful implementation and function in damaged
      tissues. However, the lack of bio- and mechano-analytical methods to investigate
      and probe the initial processes on the interface, especially in 3D, raises the
      need for applying new experimental techniques. In our study, optical tweezers
      combined with confocal fluorescence microscopy were optimized to investigate the
      initial cell-scaffold contact and to investigate its correlation with the
      material-dependent cell growth. By the optical tweezers-induced cell manipulation
      accompanied by force detection up to 100 pN and position detection by
      fluorescence microscopy, accurate adhesion dynamics and strength analysis was
      implemented, where several attachment sites were formed on the interface in the
      first few seconds. More importantly, we have shown that dynamics of cell adhesion
      on scaffold surfaces correlates with cell growth on the days scale, which
      indicates that the first seconds of the contact could markedly direct further
      cell response. Such a contact dynamics analysis on 3D scaffold surfaces, applied
      for the first time, can thus serve to predict scaffold biocompatibility. 

PMID- 25764168
TI  - The Evolution of Cystic Fibrosis Care.
AB  - Cystic fibrosis (CF) is the most common life-limiting inherited illness of
      whites. Most of the morbidity and mortality in CF stems from impaired mucociliary
      clearance leading to chronic, progressive airways obstruction and damage.
      Significant progress has been made in the care of patients with CF, with advances
      focused on improving mucociliary clearance, minimizing inflammatory damage, and
      managing infections; these advances include new antimicrobial therapies,
      mucolytic and osmotic agents, and antiinflammatory treatments. More recently,
      researchers have targeted disease-causing mutations using therapies to promote
      gene transcription and improve channel function, which has led to impressive
      physiologic changes in some patients. As we develop more advanced, allele
      directed therapies for the management of CF, it will become increasingly
      important to understand the specific genetic and environmental interactions that
      cause the significant heterogeneity of lung disease seen in the CF population.
      This understanding of CF endotypes will allow for more targeted, personalized
      therapies for future patients. This article reviews the genetic and molecular
      basis of CF lung disease, the treatments currently available, and novel therapies
      that are in development. 

PMID- 25764170
TI  - Adaptive robust genetic association tests using case-parents triad families.
AB  - Using the conditional likelihood, a model-specific score test can be derived
      under a given genetic model to test genetic association for case-parents triad
      family data. When the underlying genetic model is correctly specified, the score
      test is most powerful. However, it can lose substantial power when the model is
      misspecified. Several robust tests have been proposed to deal with the problem,
      such as the maximum test statistic, the maximin efficiency robust test, and the
      constrained likelihood ratio test. These tests have been shown to be robust
      against model misspecification compared with those model-specific score tests,
      but they are either time-consuming in computation or not sufficiently high in
      power robustness under some situations. In this study, a data-driven procedure is
      proposed to construct two adaptive robust genetic association tests WMERT and
      WMAX . The WMERT is simple in calculation and has fairly high power robustness.
      The empirical power of WMAX is quite stable and close to those of the model
      specific score tests. The two proposed tests should be beneficial to practical
      genetic association studies. A real dataset consisting of neural tube defect
      triad families is used for illustration of the methods. R-scripts are also
      provided for numerical calculation of the proposed methods in practical studies. 

PMID- 25764172
TI  - Anticoagulants for acute ischaemic stroke.
AB  - BACKGROUND: Most ischaemic strokes are caused by a blood clot blocking an artery
      in the brain. Clot prevention with anticoagulants might improve outcomes if
      bleeding risks are low. This is an update of a Cochrane review first published in
      1995, with recent updates in 2004 and 2008. OBJECTIVES: To assess the
      effectiveness and safety of early anticoagulation (within the first 14 days of
      onset) in people with acute presumed or confirmed ischaemic stroke. SEARCH
      METHODS: We searched the Cochrane Stroke Group Trials Register (June 2014), the
      Cochrane Central Register of Controlled Trials (CENTRAL), the Cochrane Database
      of Systematic Reviews (CDSR), the Database of Reviews of Effects (DARE) and the
      Health Technology Assessment Database (HTA) (The Cochrane Library 2014 Issue 6),
      MEDLINE (2008 to June 2014) and EMBASE (2008 to June 2014). In addition, we
      searched ongoing trials registries and reference lists of relevant papers. For
      previous versions of this review, we searched the register of the Antithrombotic
      Trialists' (ATT) Collaboration, consulted MedStrategy (1995), and contacted
      relevant drug companies. SELECTION CRITERIA: Randomised trials comparing early
      anticoagulant therapy (started within two weeks of stroke onset) with control in
      people with acute presumed or confirmed ischaemic stroke. DATA COLLECTION AND
      ANALYSIS: Two review authors independently selected trials for inclusion,
      assessed trial quality, and extracted the data. MAIN RESULTS: We included 24
      trials involving 23,748 participants. The quality of the trials varied
      considerably. The anticoagulants tested were standard unfractionated heparin, low
      molecular-weight heparins, heparinoids, oral anticoagulants, and thrombin
      inhibitors. Over 90% of the evidence relates to the effects of anticoagulant
      therapy initiated within the first 48 hours of onset. Based on 11 trials (22,776
      participants) there was no evidence that anticoagulant therapy started within the
      first 14 days of stroke onset reduced the odds of death from all causes (odds
      ratio (OR) 1.05; 95% confidence interval (CI) 0.98 to 1.12) at the end of follow
      up. Similarly, based on eight trials (22,125 participants), there was no evidence
      that early anticoagulation reduced the odds of being dead or dependent at the end
      of follow-up (OR 0.99; 95% CI 0.93 to 1.04). Although early anticoagulant therapy
      was associated with fewer recurrent ischaemic strokes (OR 0.76; 95% CI 0.65 to
      0.88), it was also associated with an increase in symptomatic intracranial
      haemorrhages (OR 2.55; 95% CI 1.95 to 3.33). Similarly, early anticoagulation
      reduced the frequency of symptomatic pulmonary emboli (OR 0.60; 95% CI 0.44 to
      0.81), but this benefit was offset by an increase in extracranial haemorrhages
      (OR 2.99; 95% CI 2.24 to 3.99). AUTHORS' CONCLUSIONS: Since the last version of
      the review, no new relevant studies have been published and so there is no
      additional information to change the conclusions. Early anticoagulant therapy is
      not associated with net short- or long-term benefit in people with acute
      ischaemic stroke. Treatment with anticoagulants reduced recurrent stroke, deep
      vein thrombosis and pulmonary embolism, but increased bleeding risk. The data do
      not support the routine use of any of the currently available anticoagulants in
      acute ischaemic stroke.

PMID- 25764171
TI  - Beyond iron: non-classical biological functions of bacterial siderophores.
AB  - Bacteria secrete small molecules known as siderophores to acquire iron from their
      surroundings. For over 60 years, investigations into the bioinorganic chemistry
      of these molecules, including fundamental coordination chemistry studies, have
      provided insight into the crucial role that siderophores play in bacterial iron
      homeostasis. The importance of understanding the fundamental chemistry underlying
      bacterial life has been highlighted evermore in recent years because of the
      emergence of antibiotic-resistant bacteria and the need to prevent the global
      rise of these superbugs. Increasing reports of siderophores functioning in
      capacities other than iron transport have appeared recently, but reports of "non
      classical" siderophore functions have long paralleled those of iron transport.
      One particular non-classical function of these iron chelators, namely antibiotic
      activity, was documented before the role of siderophores in iron transport was
      established. In this Perspective, we present an exposition of past and current
      work into non-classical functions of siderophores and highlight the directions in
      which we anticipate that this research is headed. Examples include the ability of
      siderophores to function as zincophores, chalkophores, and metallophores for a
      variety of other metals, sequester heavy metal toxins, transport boron, act as
      signalling molecules, regulate oxidative stress, and provide antibacterial
      activity. 

PMID- 25764174
TI  - HIV/AIDS in Lebanese prisons: challenges and proposed actions.
AB  - PURPOSE: The purpose of this paper is to discuss the extent of human
      immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) crisis in
      Lebanese prisons, propose functional reforms for Roumieh prisons (the country's
      largest male top-security prison), and outline the main challenges to HIV/AIDS
      prevention, intervention, and treatment. DESIGN/METHODOLOGY/APPROACH: All
      recommendations were based on previous successful stories, international prison
      standards as well as cultural considerations. FINDINGS: This paper argues that
      prevention and interventions starts within the prison community including
      inmates, guards, and other prison and provision of appropriate health care,
      education, and prison infrastructure. SOCIAL IMPLICATIONS: These strategies are
      not only important in limiting prevention and transmission of HIV/AIDS, but also
      contribute in optimizing quality of life within the prison system.
      ORIGINALITY/VALUE: This paper is the first of its kind to discuss the prison
      situation in Lebanese prisons in terms of public health promotion and reforms.

PMID- 25764175
TI  - Mental health in-reach in an urban UK remand prison.
AB  - PURPOSE: Prison mental health in-reach teams (MHITs) have developed in England
      and Wales over the last decade. Services have been nationally reviewed, but
      detailed descriptions of their work have been scarce. The purpose of this paper
      is to describe the functions of one MHIT in a busy, ethnically diverse, male
      remand prison in London, UK. DESIGN/METHODOLOGY/APPROACH: Clinical and
      demographic data were collected for prisoners referred to the MHIT using a
      retrospective design over an 18-week period in 2008/2009 (n=111). FINDINGS:
      Foreign national prisoners and sentenced prisoners were significantly under
      referred. Most referrals were already known to community mental health services,
      although around a quarter accessed services for the first time in prison. Around
      a third presented with self-harm/suicide risks. Substance misuse problems were
      common. Although the MHIT had evolved systems to promote service access, prisoner
      self-referrals were limited. PRACTICAL IMPLICATIONS: Foreign national prisoners
      require enhanced investment to improve service access. MHITs identify people with
      mental disorders for the first time in prisons, but better screening arrangements
      are needed across systems. An evaluation of multiple MHIT models could inform a
      wider delivery template. Originality/value - One of the first ground-level
      evaluations of MHITs in England and Wales.

PMID- 25764173
TI  - Impaired systemic tetrahydrobiopterin bioavailability and increased oxidized
      biopterins in pediatric falciparum malaria: association with disease severity.
AB  - Decreased bioavailability of nitric oxide (NO) is a major contributor to the
      pathophysiology of severe falciparum malaria. Tetrahydrobiopterin (BH4) is an
      enzyme cofactor required for NO synthesis from L-arginine. We hypothesized that
      systemic levels of BH4 would be decreased in children with cerebral malaria,
      contributing to low NO bioavailability. In an observational study in Tanzania, we
      measured urine levels of biopterin in its various redox states (fully reduced
      [BH4] and the oxidized metabolites, dihydrobiopterin [BH2] and biopterin [B0]) in
      children with uncomplicated malaria (UM, n = 55), cerebral malaria (CM, n = 45),
      non-malaria central nervous system conditions (NMC, n = 48), and in 111 healthy
      controls (HC). Median urine BH4 concentration in CM (1.10 [IQR:0.55-2.18]
      MUmol/mmol creatinine) was significantly lower compared to each of the other
      three groups - UM (2.10 [IQR:1.32-3.14];p<0.001), NMC (1.52 [IQR:1.01-2.71];p =
      0.002), and HC (1.60 [IQR:1.15-2.23];p = 0.005). Oxidized biopterins were
      increased, and the BH4:BH2 ratio markedly decreased in CM. In a multivariate
      logistic regression model, each Log10-unit decrease in urine BH4 was
      independently associated with a 3.85-fold (95% CI:1.89-7.61) increase in odds of
      CM (p<0.001). Low systemic BH4 levels and increased oxidized biopterins
      contribute to the low NO bioavailability observed in CM. Adjunctive therapy to
      regenerate BH4 may have a role in improving NO bioavailability and microvascular
      perfusion in severe falciparum malaria.

PMID- 25764176
TI  - "Seek, test, treat and retain" for hepatitis C in the United States criminal
      justice system.
AB  - PURPOSE: The purpose of this paper is to consider the potential benefits and
      challenges of applying a strategy of "seek, test, treat and retain" (STTR) to
      hepatitis C virus (HCV) in the US criminal justice system.
      DESIGN/METHODOLOGY/APPROACH: The authors draw on the published literature to
      illustrate how each component of STTR could be applied to HCV in the US criminal
      justice system, and describe challenges to the implementation of this strategy.
      FINDINGS: The burden of morbidity and mortality associated with chronic HCV
      infection in the USA is increasing and without significantly increased treatment
      uptake, will likely continue to do so for several decades. The authors argue that
      the US criminal justice system is an ideal focus for HCV case finding and
      treatment due to a high prevalence of infection and large volume of individuals
      in contact with this system. STTR would identify large numbers of HCV infections,
      leading to opportunities for secondary prevention and primary care. Important
      challenges to the implementation of STTR include treatment costs and training of
      prison medical providers. ORIGINALITY/VALUE: This paper highlights opportunities
      to address HCV in the US criminal justice system.

PMID- 25764177
TI  - Palliative and end-of-life care in prisons: a content analysis of the literature.
AB  - PURPOSE: The growing numbers of terminally ill and dying in prison has high
      economic and moral costs as global correctional systems and the society at large.
      However, to date little is known about the extent to which palliative and end-of
      life care is infused within global prison health care systems. The purpose of
      this paper is to fill a gap in the literature by reviewing and critically
      appraising the methods and major findings of the international peer-reviewed
      literature on palliative and end-of-life care in prison, identify the common
      elements of promising palliative and end-of-life services in prison, and what
      factors facilitate or create barrier to implementation.
      DESIGN/METHODOLOGY/APPROACH: A content analysis was conducted of the existing
      peer-reviewed literature on palliative and end-of-life care in prison. English
      language articles were located through a comprehensive search of peer-reviewed
      journals, such as Academic Search Premier Literature databases using differing
      combinations of key word search terms, "prison," "palliative care," and "end-of
      life care." A total of 49 studies published between 1991 and 2013 met criteria
      for sample inclusion. Deductive and inductive analysis techniques were used to
      generate frequency counts and common themes related to the methods and major
      findings. FINDINGS: The majority (n=39) of studies were published between 2001
      2013 in the USA (n=40) and the UK (n=7). Most were about US prison hospice
      programs (n=16) or barriers to providing palliative and end of life care in
      prisons (n=10). The results of the inductive analysis identified common elements
      of promising practices, which included the use of peer volunteers, multi
      disciplinary teams, staff training, and partnerships with community hospices.
      Obstacles identified for infusing palliative and end-of-life care in prison
      included ethical dilemmas based on custody vs care, mistrust between staff and
      prisoners, safety concerns, concern over prisoners' potential misuse of pain
      medication, and institutional, staff, and public apathy toward terminally ill
      prisoners and their human rights to health in the form of compassionate and
      palliative care, including the use of compassionate release laws. RESEARCH
      LIMITATIONS/IMPLICATIONS: Implications for future research that foster human
      rights and public awareness of the economic and moral costs of housing the sick
      and dying in prisons. More research is needed to document human rights violations
      as well as best practices and evidence-based practices in palliative and end-of
      life care in prisons. Future studies should incorporate data from the terminally
      ill in prison, peer supports, and family members. Future studies also should
      employ more rigorous research designs to evaluate human rights violations, staff
      and public attitudes, laws and policies, and best practices. Quantitative studies
      that use experimental designs, longitudinal data, and multiple informants are
      needed. Qualitative data would allow for thick descriptions of key stakeholders
      experiences, especially of the facilitators and barriers for implementing policy
      reform efforts and palliative care in prisons. Practical implications - This
      review provides a foundation on which to build on about what is known thus far
      about the human right to health, especially parole policy reform and infusing
      palliative and end-of-life care for the terminally ill and dying in prisons. This
      information can be used to develop or improve a new generation research,
      practice, policy, and advocacy efforts for that target terminally ill and dying
      in prison and their families and communities. SOCIAL IMPLICATIONS: There are
      significant social implications to this review. From a human rights perspective,
      the right to freedom from torture and cruel and unusual punishment is a
      fundamental human right along with prisoners' rights for an appropriate level of
      health care. These rights should be guaranteed regardless of the nature of their
      crime or whether they are in a prison placement. The information provided in this
      review can be used to educate and possible transform individual's and society's
      views toward the terminally ill and dying who are involved in the criminal
      justice system. ORIGINALITY/VALUE: This paper extends the extant literature by
      using both quantitative and qualitative analysis methods to organize, summarize,
      and critically analyze the international literature on palliative care and end of
      life care in prison. This review is designed to increase awareness among the
      international community of the pain and suffering of the terminally ill in prison
      and the facilitators and barriers to providing them compassionate care while in
      custody.

PMID- 25764178
TI  - Managing pain in prison: staff perspectives.
AB  - PURPOSE: The purpose of this paper is to present the findings of one part of a
      larger study, funded by the National Institute for Health Research, which
      explored the management of pain in adult male prisoners in one large category B
      prison in England. In this paper, the authors focus on the attitudes and
      perceptions of prison staff towards pain management in prison.
      DESIGN/METHODOLOGY/APPROACH: A qualitative design was utilised to explore the
      staff perceptions of pain and pain management in one adult male prison.
      Questionnaires were provided for all staff with prisoner contact, and a follow up
      focus group was undertaken to further explore questionnaire data. FINDINGS: The
      questionnaire and focus group findings demonstrated that staff had a good
      awareness of pain and pain management in prison, with both physical and emotional
      pain identified. The frequency of approaches by prisoners to staff for pain
      relief was noted to be high, whilst awareness of how the prison environment could
      potentially exacerbate pain was discussed. The acquisition of analgesia by
      prisoners for secondary gain was identified as a challenge to both assessing
      levels of pain and providing pain relief in prison, illustrating the complexity
      of providing care within a custodial culture. The effect on staff of caring for
      prisoners found to be confrontational and deceitful was significant for
      participants, with feelings of anger and frustration reported. Research
      LIMITATIONS/IMPLICATIONS: This study was undertaken in one adult male category B
      prison with a very high turnover of prisoners. Staff working in other types of
      prison, for example, higher security or those more stable with longer sentenced
      prisoners could provide alternative views, as may staff caring for younger
      offenders and women. The challenges to undertaking research in prison with staff
      who can understandably be reluctant to engage in reflection on their practice
      cannot be underestimated and impact significantly on available methodologies.
      ORIGINALITY/VALUE: This qualitative research is the first of its kind to offer
      the perspectives of both health care professionals and prison staff working with
      prisoners complaining of pain in an English prison. It provides the groundwork
      for further research and development.

PMID- 25764179
TI  - Resistance to gray leaf spot of maize: genetic architecture and mechanisms
      elucidated through nested association mapping and near-isogenic line analysis.
AB  - Gray leaf spot (GLS), caused by Cercospora zeae-maydis and Cercospora zeina, is
      one of the most important diseases of maize worldwide. The pathogen has a
      necrotrophic lifestyle and no major genes are known for GLS. Quantitative
      resistance, although poorly understood, is important for GLS management. We used
      genetic mapping to refine understanding of the genetic architecture of GLS
      resistance and to develop hypotheses regarding the mechanisms underlying
      quantitative disease resistance (QDR) loci. Nested association mapping (NAM) was
      used to identify 16 quantitative trait loci (QTL) for QDR to GLS, including seven
      novel QTL, each of which demonstrated allelic series with significant effects
      above and below the magnitude of the B73 reference allele. Alleles at three QTL,
      qGLS1.04, qGLS2.09, and qGLS4.05, conferred disease reductions of greater than
      10%. Interactions between loci were detected for three pairs of loci, including
      an interaction between iqGLS4.05 and qGLS7.03. Near-isogenic lines (NILs) were
      developed to confirm and fine-map three of the 16 QTL, and to develop hypotheses
      regarding mechanisms of resistance. qGLS1.04 was fine-mapped from an interval of
      27.0 Mb to two intervals of 6.5 Mb and 5.2 Mb, consistent with the hypothesis
      that multiple genes underlie highly significant QTL identified by NAM. qGLS2.09,
      which was also associated with maturity (days to anthesis) and with resistance to
      southern leaf blight, was narrowed to a 4-Mb interval. The distance between major
      leaf veins was strongly associated with resistance to GLS at qGLS4.05. NILs for
      qGLS1.04 were treated with the C. zeae-maydis toxin cercosporin to test the role
      of host-specific toxin in QDR. Cercosporin exposure increased expression of a
      putative flavin-monooxygenase (FMO) gene, a candidate detoxification-related gene
      underlying qGLS1.04. This integrated approach to confirming QTL and
      characterizing the potential underlying mechanisms advances the understanding of
      QDR and will facilitate the development of resistant varieties. 

PMID- 25764181
TI  - Palmitic Acid and Health: Introduction.
AB  - Interest in the dietary role and metabolic effect of saturated fatty acids has
      been recently renewed on the basis of epidemiologic observations and economical
      approach to health and well-being. Saturated fats may favorably increase blood
      HDL-Cholesterol levels without significant changes of the total cholesterol/HDL
      Cholesterol ratio. Also, the negative effect of saturated fat on cardiovascular
      diseases risk has recently been challenged. Palmitic acid, among all, may have
      special structural and functional roles in utero and in infancy, and indeed is it
      is being delivered in a unique form in human milk. Future research should include
      objective cost-benefit analyses when disentangling the role of saturated fats in
      dietary recommendations. 

PMID- 25764180
TI  - Controversies in the natural history of congenital human cytomegalovirus
      infection: the paradox of infection and disease in offspring of women with
      immunity prior to pregnancy.
AB  - Human cytomegalovirus (HCMV) is the most common virus infection in the developing
      fetus. A fraction of infants infected in utero develop significant life
      threatening and organ-threatening disease with over 90% of infected infants
      exhibiting no clinical evidence of infection in the newborn period. However,
      about 10% of all infected infants will develop long-term sequelae. Early studies
      stressed the importance of primary maternal HCMV infection during pregnancy as a
      critical determinant of intrauterine transmission and outcome. This concept
      serves as the foundation for the development of prophylactic vaccines and
      biologics such as HCMV immune globulins. More recently, studies in maternal
      populations with high HCMV seroprevalence have challenged the concept of
      protective maternal immunity. Findings from multiple studies suggest that
      preexisting maternal HCMV immunity provides at best, partial protection from
      disease in the infected offspring and similarly may have limited impact on
      intrauterine transmission. This brief review will provide some considerations
      about the apparent paradox of maternal HCMV immunity and congenital infection.

PMID- 25764182
TI  - Condition-related predictors of successful transition from paediatric to adult
      care among adolescents with Type 1 diabetes.
AB  - AIMS: To describe patient attendance for adult treatment after completion by
      young people of a structured Diabetes Transition Clinic and to identify the
      predictors of non-attendance at adult clinics by young people with Type 1
      diabetes transitioning from paediatric care. METHODS: Young people with Type 1
      diabetes were consecutively enrolled on a Diabetes Transition Clinic programme at
      a Canadian paediatric teaching hospital, beginning in December 2007. Data from
      clinical interviews completed by an adolescent medicine specialist and an adult
      endocrinologist were prospectively collected at the Diabetes Transition Clinic
      visit in the patient's 18(th) year, before he/she was transferred at age 18 years
      to the adult clinic and at the first adult clinic visit. RESULTS: As of June
      2011, 136 young people participating in the Diabetes Transition Clinic programme
      had been discharged from paediatric care at least 1 year earlier. Of these, 43
      participants were lost to follow-up. Loss to follow-up was more frequent among:
      those who were diagnosed with diabetes before the age of 12 years; those who were
      taking insulin twice or three times daily rather than by pump or multiple daily
      injections; those who had higher HbA1c levels; those who had fewer diabetes
      physician visits in the year preceding the Diabetes Transition Clinic visit; and
      those who did not ask questions at the Diabetes Transition Clinic visit.
      CONCLUSIONS: Several factors easily ascertained at a clinical encounter before
      transition can predict the likelihood of attendance in adult care, including age
      at diagnosis, mode of insulin administration, frequency of physician visits, and
      questions asked by patients during a transition visit.

PMID- 25764184
TI  - Far-infrared spectroscopy of salt penetration into a collagen fiber scaffold.
AB  - We employed far-infrared spectroscopy to observe the amount of salt that
      penetrates into collagen fiber masses. The absorption properties of collagen
      sheets prepared from tilapia skin, bovine skin, rat tail, and sea cucumber dermis
      were measured using a transmission Fourier transform spectrometer in a band from
      approximately 100 to 700 cm(-1). We confirmed that the absorbance spectra of the
      four types of dried collagen sheet show good agreement, even though the amino
      acid compositions differed. The absorbance peaks observed in the band
      corresponded to collective vibrations of plural functional groups such as
      methylene and imino groups in collagen. When salt solution was added to the
      collagen sheets and then dried, the spectral shapes of the sheets at
      approximately 166 cm(-1) were clearly different from those of the plain collagen
      sheets. The differential absorbance between wavenumbers 166 cm(-1) and 250 cm(-1)
      sensitively reflected the difference between higher-order structures, and the
      salt diffusion (crystallization) depended on the collagen fiber condition. From
      these results, we consider that spectral changes can be used for the numerical
      evaluation of salt penetration into a collagen fiber scaffold.

PMID- 25764183
TI  - Condensin HEAT subunits required for DNA repair, kinetochore/centromere function
      and ploidy maintenance in fission yeast.
AB  - Condensin, a central player in eukaryotic chromosomal dynamics, contains five
      evolutionarily-conserved subunits. Two SMC (structural maintenance of
      chromosomes) subunits contain ATPase, hinge, and coiled-coil domains. One non-SMC
      subunit is similar to bacterial kleisin, and two other non-SMC subunits contain
      HEAT (similar to armadillo) repeats. Here we report isolation and
      characterization of 21 fission yeast (Schizosaccharomyces pombe) mutants for
      three non-SMC subunits, created using error-prone mutagenesis that resulted in
      single-amino acid substitutions. Beside condensation, segregation, and DNA repair
      defects, similar to those observed in previously isolated SMC and cnd2 mutants,
      novel phenotypes were observed for mutants of HEAT-repeats containing Cnd1 and
      Cnd3 subunits. cnd3-L269P is hypersensitive to the microtubule poison,
      thiabendazole, revealing defects in kinetochore/centromere and spindle assembly
      checkpoints. Three cnd1 and three cnd3 mutants increased cell size and doubled
      DNA content, thereby eliminating the haploid state. Five of these mutations
      reside in helix B of HEAT repeats. Two non-SMC condensin subunits, Cnd1 and Cnd3,
      are thus implicated in ploidy maintenance. 

PMID- 25764186
TI  - An ongoing measles outbreak in the Federation of Bosnia and Herzegovina, 2014 to
      2015.
AB  - Between January 2014 and the beginning of February 2015, the Federal Institute of
      Public Health in the Federation of Bosnia and Herzegovina has reported 3,804
      measles cases. Notable transmission has been observed in three Central Bosnia
      Canton municipalities: Bugojno, Fojnica and Travnik. Most cases were unvaccinated
      2,680 (70%) or of unknown vaccination status 755 (20%). Health authorities have
      been checking vaccination records and performing necessary prevention measures.
      The epidemic is still ongoing.

PMID- 25764185
TI  - V-myc immortalizes human neural stem cells in the absence of pluripotency
      associated traits.
AB  - A better understanding of the molecular mechanisms governing stem cell self
      renewal will foster the use of different types of stem cells in disease modeling
      and cell therapy strategies. Immortalization, understood as the capacity for
      indefinite expansion, is needed for the generation of any cell line. In the case
      of v-myc immortalized multipotent human Neural Stem Cells (hNSCs), we
      hypothesized that v-myc immortalization could induce a more de-differentiated
      state in v-myc hNSC lines. To test this, we investigated the expression of
      surface, biochemical and genetic markers of stemness and pluripotency in v-myc
      immortalized and control hNSCs (primary precursors, that is, neurospheres) and
      compared these two cell types to human Embryonic Stem Cells (hESCs) and
      fibroblasts. Using a Hierarchical Clustering method and a Principal Component
      Analysis (PCA), the v-myc hNSCs associated with their counterparts hNSCs (in the
      absence of v-myc) and displayed a differential expression pattern when compared
      to hESCs. Moreover, the expression analysis of pluripotency markers suggested no
      evidence supporting a reprogramming-like process despite the increment in
      telomerase expression. In conclusion, v-myc expression in hNSC lines ensures self
      renewal through the activation of some genes involved in the maintenance of stem
      cell properties in multipotent cells but does not alter the expression of key
      pluripotency-associated genes. 

PMID- 25764187
TI  - Opportunistic testing for urogenital infection with Chlamydia trachomatis in
      south-western Switzerland, 2012: a feasibility study.
AB  - The feasibility of opportunistic screening of urogenital infections with
      Chlamydia trachomatis was assessed in a cross-sectional study in 2012, in two
      cantons of south-western Switzerland: Vaud and Valais. Sexually active persons
      younger than 30 years, not tested for C. trachomatis in the last three months,
      were invited for free C. trachomatis testing by PCR in urine or self-applied
      vaginal swabs. Of 2,461 consenting participants, 1,899 (77%) were women and all
      but six (0.3%) submitted a sample. Forty-seven per cent of female and 25% of male
      participants were younger than 20 years. Overall, 134 (5.5%) of 2,455 tested
      participants had a positive result and were followed up. Seven per cent of all
      candidates for screening were not invited, 10% of invited candidates were not
      eligible, 15% of the eligible candidates declined participation, 5% of tested
      participants testing positive were not treated, 29% of those treated were not
      retested after six months and 9% of those retested were positive for C.
      trachomatis. Opportunistic C. trachomatis testing proved technically feasible and
      acceptable, at least if free of charge. Men and peripheral rural regions were
      more difficult to reach. Efforts to increase testing and decrease dropout at all
      stages of the screening procedure are necessary.

PMID- 25764188
TI  - Characteristics and practices of National Immunisation Technical Advisory Groups
      in Europe and potential for collaboration, April 2014.
AB  - In many countries, national vaccination recommendations are developed by
      independent expert committees, so-called national immunisation technical advisory
      groups (NITAG). Since the evaluation of vaccines is complex and resource
      demanding, collaboration between NITAGs that evaluate the same vaccines could be
      beneficial. We conducted a cross-sectional survey among 30 European countries in
      February 2014, to explore basic characteristics and current practices of European
      NITAGs and identify potential modes and barriers for collaboration. Of 28
      responding countries, 26 reported to have a NITAG or an equivalent expert group.
      Of these, 20 apply a systematic approach in the vaccine decision-making process,
      e.g. by considering criteria such as country-specific disease epidemiology,
      vaccine efficacy/effectiveness/safety, health economics, programme
      implementation/logistics or country-specific values/preferences. However, applied
      frameworks and extent of evidence review differ widely. The use of systematic
      reviews is required for 15 of 26 NITAGs, while results from transmission
      modelling and health economic evaluations are routinely considered by 18 and 20
      of 26 NITAGs, respectively. Twenty-five countries saw potential for NITAG
      collaboration, but most often named structural concerns, e.g. different NITAG
      structures or countries' healthcare systems. Our survey gathered information that
      can serve as an inventory on European NITAGs, allowing further exploration of
      options and structures for NITAG collaboration.

PMID- 25764189
TI  - Measles outbreak linked to an international dog show in Slovenia - primary cases
      and chains of transmission identified in Italy, November to December 2014.

PMID- 25764190
TI  - Authors response: Measles outbreak linked to an international dog show in
      Slovenia, 2014.

PMID- 25764191
TI  - Trends in human leptospirosis in Denmark, 1980 to 2012.

PMID- 25764192
TI  - Trends in human leptospirosis in Denmark, 1980 to 2012.

PMID- 25764193
TI  - WHO recommendations on the composition of the 2015/16 influenza virus vaccines in
      the northern hemisphere.

PMID- 25764197
TI  - Dental Mesenchymal Stem Cells in Inflamed Microenvironment: Potentials and
      Challenges for Regeneration.
AB  - Adult dental mesenchymal stem cells (DMSCs) are multi-potent stem cells that are
      involved in dental tissue repair and regeneration. DMSCs are able to
      differentiate into multiple lineages, including odontogenic, osteogenic,
      neurogenic, adipogenic, chondrogenic, hepatogenic lineages and insulinproducing
      cells. However, the DMSCs from functioning, impacted or exfoliated teeth may not
      be available when needed. Recently, DMSCs have been found in pulpal, periapical
      and periodontal tissue with inflammation from deciduous and immature/mature
      permanent teeth. DMSCs from inflamed tissue (iDMSCs) possess typical stem cell
      characteristics while they showing varied properties. Whether iDMSCs are
      comparable to healthy DMSCs and can be used for regeneration are not clear.
      Studies on the impact of infection/inflammation in the local microenvironment on
      DMSCs are widely conducted to investigate the specific influences and underlying
      mechanisms in vitro and in vivo. In this review, we introduced the discovery of
      iDMSCs from different sources, and also discussed the influence of dental
      inflammation and associated immune responses, particularly the effect from
      lipopolysaccharide (LPS) stimulation, on local DMSCs. In addition, the effects of
      dental procedures and materials on DMSCs are discussed. 

PMID- 25764198
TI  - Expression and Function of MicroRNAs in Enamel Development.
AB  - MicroRNAs (miRNAs) are short (~21nt), noncoding, and single-stranded RNAs that
      can negatively regulate gene expression by binding to 3'UTRs of target mRNAs
      sequence-specifically to affect their translation and/or stability. MiRNAs are
      involved in multiple developmental events in various tissues and organs. Such
      events include dental enamel development. This review focuses on the expression
      and functions of miRNAs regulated in enamel development. This study further
      discusses the possible participation of signaling pathways affected by miRNAs
      during stem cell proliferation or renewal, cell differentiation, and cusp
      patterning formation. Research on the enamel developmental process and miRNA
      regulation mechanisms can facilitate better understanding of clinical enamel
      malformation and provide potential therapeutic schemes. 

PMID- 25764196
TI  - Organ culture bioreactors--platforms to study human intervertebral disc
      degeneration and regenerative therapy.
AB  - In recent decades the application of bioreactors has revolutionized the concept
      of culturing tissues and organs that require mechanical loading. In
      intervertebral disc (IVD) research, collaborative efforts of biomedical
      engineering, biology and mechatronics have led to the innovation of new loading
      devices that can maintain viable IVD organ explants from large animals and human
      cadavers in precisely defined nutritional and mechanical environments over
      extended culture periods. Particularly in spine and IVD research, these organ
      culture models offer appealing alternatives, as large bipedal animal models with
      naturally occurring IVD degeneration and a genetic background similar to the
      human condition do not exist. Latest research has demonstrated important concepts
      including the potential of homing of mesenchymal stem cells to nutritionally or
      mechanically stressed IVDs, and the regenerative potential of "smart"
      biomaterials for nucleus pulposus or annulus fibrosus repair. In this review, we
      summarize the current knowledge about cell therapy, injection of cytokines and
      short peptides to rescue the degenerating IVD. We further stress that most
      bioreactor systems simplify the real in vivo conditions providing a useful proof
      of concept. Limitations are that certain aspects of the immune host response and
      pain assessments cannot be addressed with ex vivo systems. Coccygeal animal disc
      models are commonly used because of their availability and similarity to human
      IVDs. Although in vitro loading environments are not identical to the human in
      vivo situation, 3D ex vivo organ culture models of large animal coccygeal and
      human lumbar IVDs should be seen as valid alternatives for screening and
      feasibility testing to augment existing small animal, large animal, and human
      clinical trial experiments. 

PMID- 25764199
TI  - Role of the Epithelial Cell Rests of Malassez in Periodontal Homeostasis and
      Regeneration - A Review.
AB  - Predictable and complete periodontal regeneration following periodontitis has
      been the ultimate goal of periodontal treatment. It has been recognized that
      Hertwig's epithelial root sheath (HERS) cells play a crucial role in
      cementogenesis and root formation. As the descendants of HERS and unique
      odontogenic epithelium in the adult periodontium, epithelial cell rests of
      Malassez (ERM) have long been considered as quiescent epithelial remnants devoid
      of structure and function. Here we will present an overview of our present
      understanding and putative functions of the ERM in the regeneration of
      periodontal tissues. 

PMID- 25764200
TI  - Neck muscle fatigue alters upper limb proprioception.
AB  - Limb proprioception is an awareness by the central nervous system (CNS) of the
      location of a limb in three-dimensional space and is essential for movement and
      postural control. The CNS uses the position of the head and neck when
      interpreting the position of the upper limb, and altered input from neck muscles
      may affect the sensory inputs to the CNS and consequently may impair the
      awareness of upper limb joint position. The purpose of this study was to
      determine whether fatigue of the cervical extensors muscles (CEM) using a
      submaximal fatigue protocol alters the ability to recreate a previously presented
      elbow angle with the head in a neutral position. Twelve healthy individuals
      participated. CEM activity was examined bilaterally using surface
      electromyography, and kinematics of the elbow joint was measured. The fatigue
      protocol included an isometric neck extension task at 70 % of maximum until
      failure. Joint position error increased following fatigue, demonstrating a
      significant main effect of time (F 2, 18 = 19.41, p <= 0.0001) for absolute
      error. No significant differences were found for variable error (F 2, 18 = 0.27,
      p = 0.76) or constant error (F 2, 18 = 1.16 of time, p <= 0.33). This study
      confirms that fatigue of the CEM can reduce the accuracy of elbow joint position
      matching. This suggests that altered afferent input from the neck subsequent to
      fatigue may impair upper limb proprioception.

PMID- 25764202
TI  - Quantifying the correlation between photoplethysmography and laser Doppler
      flowmetry microvascular low-frequency oscillations.
AB  - Photoplethysmography (PPG) and laser Doppler flowmetry (LDF) are two recognized
      optical techniques that can track low-frequency perfusion changes in
      microcirculation. The aim of this study was to determine, in healthy subjects,
      the correlation between the techniques for specific low-frequency bands
      previously defined for microcirculation. Twelve healthy male subjects (age range
      18 to 50 years) were studied, with PPG and LDF signals recorded for 20 min from
      their right and left index (PPG) and middle (LDF) fingers. Wavelet analysis
      comprised dividing the low-frequency integral wavelet spectrum (IWS) into five
      established physiological bands relating to cardiac, respiratory, myogenic,
      neurogenic, and endothelial activities. The correlation between PPG and LDF was
      quantified using wavelet correlation analysis and Spearman correlation analysis
      of the median IWS amplitude. The median wavelet correlation between signals
      (right-left side average) was 0.45 (cardiac), 0.49 (respiratory), 0.86
      (myogenic), 0.91 (neurogenic), and 0.91 (endothelial). The correlation of IWS
      amplitude values (right-left side average) was statistically significant for the
      cardiac (rho = 0.64, p < 0.05) and endothelial (rho = 0.62, p < 0.05) bands. This
      pilot study has shown good correlation between PPG and LDF for specific
      physiological frequency bands. In particular, the results suggest that PPG has
      the potential to be a low-cost replacement for LDF for endothelial activity
      assessments.

PMID- 25764204
TI  - Advances in molecular diagnosis of parasitic enteropathogens.
AB  - Here, recent developments in the detection and identification of parasites
      causing enteric infection are reviewed including the utility and challenges of
      multi-target molecular assays. Difficulties in clinical interpretation arising
      from increased detection of parasites, of co-infection with other enteropathogens
      and of asymptomatic carriage are discussed. Published approaches for detection
      across a broad range of organisms are described, including commercial assays
      available to Australian laboratories. Using local data, the impact of
      introduction of modern molecular assays is assessed. In addition, recent advances
      in high density multi-target molecular platforms are discussed as potential
      platforms for increasing the scope of enteric pathogens to be detected whilst
      maintaining appropriate costs. 

PMID- 25764201
TI  - Absolute vs. weight-related maximum oxygen uptake in firefighters: fitness
      evaluation with and without protective clothing and self-contained breathing
      apparatus among age group.
AB  - During fire emergencies, firefighters wear personal protective devices (PC) and a
      self-contained breathing apparatus (S.C.B.A.) to be protected from injuries. The
      purpose of this study was to investigate the differences of aerobic level in 197
      firefighters (age: 34+/-7 yr; BMI: 24.4+/-2.3 kg.m-2), evaluated by a Queen's
      College Step field Test (QCST), performed with and without fire protective
      garments, and to analyze the differences among age groups (<25 yr; 26-30 yr, 31
      35 yr, 36-40 yr and >40 yr). Variance analysis was applied to assess differences
      (p < 0.05) between tests and age groups observed in absolute and weight-related
      values, while a correlation was examined between QCST with and without
      PC+S.C.B.A. The results have shown that a 13% of firefighters failed to complete
      the test with PC+S.C.B.A. and significant differences between QCST performed with
      and without PC+S.C.B.A. in absolute (F(1,169) = 42.6, p < 0.0001) and weight
      related (F(1,169) = 339.9, p < 0.0001) terms. A better correlation has been found
      in L*min-1 (r=0.67) than in ml*kg-1*min-1 (r=0.54). Moreover, we found
      significant differences among age groups both in absolute and weight-related
      values. The assessment of maximum oxygen uptake of firefighters in absolute term
      can be a useful tool to evaluate the firefighters' cardiovascular strain. 

PMID- 25764205
TI  - Molecular diagnosis of respiratory viruses.
AB  - The increasing availability of nucleic acid amplification tests since the 1980s
      has revolutionised our understanding of the pathogenesis, epidemiology, clinical
      and laboratory aspects of known and novel viral respiratory pathogens. High
      throughput, multiplex polymerase chain reaction is the most commonly used
      qualitative detection method, but utilisation of newer techniques such as next
      generation sequencing will become more common following significant cost
      reductions. Rapid and readily accessible isothermal amplification platforms have
      also allowed molecular diagnostics to be used in a 'point-of-care' format. This
      review focuses on the current applications and limitations of molecular diagnosis
      for respiratory viruses. 

PMID- 25764206
TI  - Contemporary genomic approaches in the diagnosis and typing of Staphylococcus
      aureus.
AB  - Staphylococcus aureus is a major human pathogen, causing disease in both
      community and healthcare settings. Over the past two decades, the epidemiology of
      S. aureus disease has changed dramatically, with the emergence and spread of
      community-associated methicillin-resistant S. aureus clones. This epidemiological
      shift, coupled with the association between delayed antimicrobial therapy and
      increased mortality in S. aureus bacteraemia, has greatly facilitated advances in
      the rapid molecular diagnosis of S. aureus. Rapid molecular testing for S. aureus
      can greatly reduce laboratory turnaround time, and in some circumstances, may
      lead to improved clinical outcomes. In addition, advances in DNA sequencing
      technology and bioinformatic analysis have shed new lights on the molecular
      epidemiology and transmission dynamics of S. aureus. In this context, we provide
      an overview of the key advances in the molecular diagnosis and typing of S.
      aureus, with a particular focus on the clinical impact and utility of genomic
      technologies. 

PMID- 25764207
TI  - Resistance mechanisms in Enterobacteriaceae.
AB  - Enterobacteriaceae are responsible for a large proportion of serious, life
      threatening infections and resistance to multiple antibiotics in these organisms
      is an increasing global public health problem. Mutations in chromosomal genes
      contribute to antibiotic resistance, but Enterobacteriaceae are adapted to
      sharing genetic material and much important resistance is due to 'mobile'
      resistance genes. Different mobile genetic elements, which have different
      characteristics, are responsible for capturing these genes from the chromosomes
      of a variety of bacterial species and moving them between DNA molecules. If
      transferred to plasmids, these resistance genes are then able to be transferred
      'horizontally' between different bacterial cells, including different species,
      and well as being transferred 'vertically' during cell division. Carriage of
      several resistance genes on the same plasmid enables a bacterial cell to acquire
      multi-resistance in a single step and means that spread of one resistance gene
      may be co-selected for by use of antibiotics other than those to which it confers
      resistance. Many different mobile genes conferring resistance to each class of
      antibiotic have been identified, complicating detection of the factors
      responsible for a particular resistance phenotype, especially when changes in
      chromosomal genes may also confer or contribute to resistance. Understanding the
      mechanisms of antibiotic resistance, and the means by which these mechanisms can
      evolve and disseminate, is important for developing ways to efficiently track the
      spread of resistance and to optimise treatment. 

PMID- 25764208
TI  - Generation and characterization of ABT-981, a dual variable domain immunoglobulin
      (DVD-Ig(TM)) molecule that specifically and potently neutralizes both IL-1alpha
      and IL-1beta.
AB  - Interleukin-1 (IL-1) cytokines such as IL-1alpha, IL-1beta, and IL-1Ra contribute
      to immune regulation and inflammatory processes by exerting a wide range of
      cellular responses, including expression of cytokines and chemokines, matrix
      metalloproteinases, and nitric oxide synthetase. IL-1alpha and IL-1beta bind to
      IL-1R1 complexed to the IL-1 receptor accessory protein and induce similar
      physiological effects. Preclinical and clinical studies provide significant
      evidence for the role of IL-1 in the pathogenesis of osteoarthritis (OA),
      including cartilage degradation, bone sclerosis, and synovial proliferation.
      Here, we describe the generation and characterization of ABT-981, a dual variable
      domain immunoglobulin (DVD-Ig) of the IgG1/k subtype that specifically and
      potently neutralizes IL-1alpha and IL-1beta. In ABT-981, the IL-1beta variable
      domain resides in the outer domain of the DVD-Ig, whereas the IL-1alpha variable
      domain is located in the inner position. ABT-981 specifically binds to IL-1alpha
      and IL-1beta, and is physically capable of binding 2 human IL-1alpha and 2 human
      IL-1beta molecules simultaneously. Single-dose intravenous and subcutaneous
      pharmacokinetics studies indicate that ABT-981 has a half-life of 8.0 to 10.4 d
      in cynomolgus monkey and 10.0 to 20.3 d in rodents. ABT-981 exhibits suitable
      drug-like-properties including affinity, potency, specificity, half-life, and
      stability for evaluation in human clinical trials. ABT-981 offers an exciting new
      approach for the treatment of OA, potentially addressing both disease
      modification and symptom relief as a disease-modifying OA drug. 

PMID- 25764209
TI  - A case of subungual melanoma with bone invasion: destructive local invasion and
      multiple skin metastases.

PMID- 25764211
TI  - Pathogen small RNAs: a new class of effectors for pathogen attacks.

PMID- 25764210
TI  - alpha-Spinasterol, a TRPV1 receptor antagonist, elevates the seizure threshold in
      three acute seizure tests in mice.
AB  - alpha-Spinasterol is a plant-derived compound which was reported to act as a
      selective antagonist for the transient receptor potential vanilloid 1 (TRPV1)
      receptor. Several studies revealed that the TRPV1 receptors might modulate
      seizure activity in animal models of seizures and epilepsy. The aim of the
      present study was to investigate the effect of alpha-spinasterol on the seizure
      threshold in three acute models of seizures, i.e., in the intravenous (i.v.)
      pentylenetetrazole (PTZ) seizure test, in the maximal electroshock seizure
      threshold (MEST) test and in the model of psychomotor seizures induced by 6 Hz
      stimulation in mice. Our results revealed significant anticonvulsant effect of
      alpha-spinasterol in all the used seizure tests. In the i.v. PTZ test,
      statistically significant elevation was noted in case of the threshold for
      myoclonic twitches (doses of 0.1-1 mg/kg) and generalized clonus seizures (doses
      of 0.5 and 1 mg/kg) but not for tonic seizures. The studied TRPV1 antagonist also
      increased the threshold for tonic hindlimb extension in the MEST (doses of 0.5
      and 1 mg/kg) and 6 Hz psychomotor seizure (doses of 0.1 and 0.5 mg/kg) tests in
      mice. Furthermore, alpha-spinasterol did not produce any significant impairment
      of motor coordination (assessed in the chimney test) and muscular strength
      (investigated in the grip-strength test) and it did not provoke significant
      changes in body temperature in mice. Based on the results of our study and the
      fact that alpha-spinasterol is characterized by good blood-brain permeability, we
      postulate further investigation of this compound to precisely evaluate mechanism
      of its anticonvulsant action and opportunity of its usage in clinical practice.

PMID- 25764213
TI  - Clinical utility of genetic and genomic services: a position statement of the
      American College of Medical Genetics and Genomics.
AB  - DISCLAIMER: These recommendations are designed primarily as an educational
      resource for medical geneticists and other health-care providers to help them
      provide quality medical genetics services. Adherence to these recommendations
      does not necessarily ensure a successful medical outcome. These recommendations
      should not be considered inclusive of all proper procedures and tests or
      exclusive of other procedures and tests that are reasonably directed to obtaining
      the same results. In determining the propriety of any specific procedure or test,
      geneticists and other clinicians should apply their own professional judgment to
      the specific clinical circumstances presented by the individual patient or
      specimen. It may be prudent, however, to document in the patient's record the
      rationale for any significant deviation from these recommendations.

PMID- 25764212
TI  - High incidence of unrecognized visceral/neurological late-onset Niemann-Pick
      disease, type C1, predicted by analysis of massively parallel sequencing data
      sets.
AB  - PURPOSE: Niemann-Pick disease type C (NPC) is a recessive, neurodegenerative,
      lysosomal storage disease caused by mutations in either NPC1 or NPC2. The
      diagnosis is difficult and frequently delayed. Ascertainment is likely incomplete
      because of both these factors and because the full phenotypic spectrum may not
      have been fully delineated. Given the recent development of a blood-based
      diagnostic test and the development of potential therapies, understanding the
      incidence of NPC and defining at-risk patient populations are important. METHOD:
      We evaluated data from four large, massively parallel exome sequencing data sets.
      Variant sequences were identified and classified as pathogenic or nonpathogenic
      based on a combination of literature review and bioinformatic analysis. This
      methodology provided an unbiased approach to determining the allele frequency.
      RESULTS: Our data suggest an incidence rate for NPC1 and NPC2 of 1/92,104 and
      1/2,858,998, respectively. Evaluation of common NPC1 variants, however, suggests
      that there may be a late-onset NPC1 phenotype with a markedly higher incidence,
      on the order of 1/19,000-1/36,000. CONCLUSION: We determined a combined incidence
      of classical NPC of 1/89,229, or 1.12 affected patients per 100,000 conceptions,
      but predict incomplete ascertainment of a late-onset phenotype of NPC1. This
      finding strongly supports the need for increased screening of potential patients.

PMID- 25764214
TI  - Ultra-orphan diseases: a quantitative analysis of the natural history of
      molybdenum cofactor deficiency.
AB  - PURPOSE: Experimental treatment with substrate replacement was successfully
      performed in single cases with molybdenum cofactor deficiency type A. The
      objective of this study was to quantitate the yet undefined natural history in
      untreated patients to ultimately benefit knowledge in experimental treatments in
      the future. METHODS: Systematic analysis of published cases with molybdenum
      cofactor deficiency. The main outcome measures were survival, initial cardinal
      disease features at onset, and diagnostic delay. RESULTS: The median survival for
      the overall population was 36 months. Initial cardinal disease features at onset
      were seizures (72%) as well as feeding difficulties (26%) and hypotonia (11%). In
      addition, developmental delay (9%), hemiplegia (2%), lens dislocation (2%), and
      hyperreflexia (1%) were reported. The median age at onset of the disease was the
      first day of life; the median age at diagnosis was 4.5 months. The median time to
      diagnosis (diagnostic delay) was 89 days. CONCLUSION: Molybdenum cofactor
      deficiency has its onset during the neonatal period and infancy. There is
      considerable diagnostic delay. Although seizures were the most frequent initial
      cardinal sign, molybdenum cofactor deficiency should be considered as a
      differential diagnosis in patients presenting with hypotonia, developmental
      delay, or feeding difficulties. The survival data will inform further natural
      history and therapeutic studies.

PMID- 25764215
TI  - Stakeholder engagement in policy development: challenges and opportunities for
      human genomics.
AB  - Along with rapid advances in human genomics, policies governing genomic data and
      clinical technologies have proliferated. Stakeholder engagement is widely lauded
      as an important methodology for improving clinical, scientific, and public health
      policy decision making. The purpose of this paper is to examine how stakeholder
      engagement is used to develop policies in genomics research and public health
      areas, as well as to identify future priorities for conducting evidence-based
      stakeholder engagements. We focus on exemplars in biobanking and newborn
      screening to illustrate a variety of current stakeholder engagement in policy
      making efforts. Each setting provides an important context for examining the
      methods of obtaining and integrating informed stakeholder voices into the policy
      making process. While many organizations have an interest in engaging
      stakeholders with regard to genomic policy issues, there is broad divergence with
      respect to the stakeholders involved, the purpose of engagements, when
      stakeholders are engaged during policy development, methods of engagement, and
      the outcomes reported. Stakeholder engagement in genomics policy development is
      still at a nascent stage. Several challenges of using stakeholder engagement as a
      tool for genomics policy development remain, and little evidence regarding how to
      best incorporate stakeholder feedback into policy-making processes is currently
      available.

PMID- 25764216
TI  - New insights into the promoterless transcription of DNA coligo templates by RNA
      polymerase III.
AB  - Chemically synthesized DNA can carry small RNA sequence information but
      converting that information into small RNA is generally thought to require large
      double-stranded promoters in the context of plasmids, viruses and genes. We
      previously found evidence that circularized oligodeoxynucleotides (coligos)
      containing certain sequences and secondary structures can template the synthesis
      of small RNA by RNA polymerase III in vitro and in human cells. By using
      immunoprecipitated RNA polymerase III we now report corroborating evidence that
      this enzyme is the sole polymerase responsible for coligo transcription. The
      immobilized polymerase enabled experiments showing that coligo transcripts can be
      formed through transcription termination without subsequent 3' end trimming. To
      better define the determinants of productive transcription, a structure-activity
      relationship study was performed using over 20 new coligos. The results show that
      unpaired nucleotides in the coligo stem facilitate circumtranscription, but also
      that internal loops and bulges should be kept small to avoid secondary
      transcription initiation sites. A polymerase termination sequence embedded in the
      double-stranded region of a hairpin-encoding coligo stem can antagonize
      transcription. Using lessons learned from new and old coligos, we demonstrate how
      to convert poorly transcribed coligos into productive templates. Our findings
      support the possibility that coligos may prove useful as chemically synthesized
      vectors for the ectopic expression of small RNA in human cells. 

PMID- 25764217
TI  - Role of YY1 in long-range chromosomal interactions regulating Th2 cytokine
      expression.
AB  - The molecular mechanism for chromatin remodeling and chromosomal interactions at
      the Th2 cytokine locus is not fully understood. Recently, we showed that
      transcription factor YY1 is critically involved in these events. This article
      discusses the possible roles of YY1 in these processes with particular emphasis
      on long-range chromosomal interactions. 

PMID- 25764218
TI  - mTOR signaling and transcriptional regulation in T lymphocytes.
AB  - The mechanistic target of rapamycin (mTOR) signaling integrates diverse
      environmental cues, including growth factors, nutrients and immunological
      signals. Activation of mTOR signaling stimulates protein synthesis and anabolic
      metabolism and coordinates cell growth, proliferation and fate decisions. In
      recent years, mTOR signaling has been linked to the entire spectrum of T cell
      biology, ranging from T cell development and activation to lineage specification
      and memory formation. Mechanistically, mTOR activation profoundly affects the
      expression and activity of many immunologically relevant transcription factors to
      propagate immune signaling and mediate effector functions. These transcription
      factors orchestrate cell metabolism (MYC, SREBPs and HIF1), lineage
      differentiation (T-bet, GATA3, RORgammat, FOXP3 and Eomesodermin) and immune
      activation and functions (NF-kappaB, FOXOs, IRF4, STATs and GFI-1). This review
      discusses how mTOR signaling, through impinging upon transcriptional factors,
      regulates T cell development, activation, and effector and memory
      differentiation. 

PMID- 25764220
TI  - Physical mechanisms behind the large scale features of chromatin organization.
AB  - We review the picture emerging from recently published models of classical
      polymer physics of the general features of chromatin large scale spatial
      organization, as revealed by microscopy and Hi-C data. 

PMID- 25764219
TI  - Advanced fluorescence microscopy methods for the real-time study of transcription
      and chromatin dynamics.
AB  - In this contribution we provide an overview of the recent advances allowed by the
      use of fluorescence microscopy methods in the study of transcriptional processes
      and their interplay with the chromatin architecture in living cells. Although the
      use of fluorophores to label nucleic acids dates back at least to about half a
      century ago, (1) two recent breakthroughs have effectively opened the way to use
      fluorescence routinely for specific and quantitative probing of chromatin
      organization and transcriptional activity in living cells: namely, the
      possibility of labeling first the chromatin loci and then the mRNA synthesized
      from a gene using fluorescent proteins. In this contribution we focus on methods
      that can probe rapid dynamic processes by analyzing fast fluorescence
      fluctuations. 

PMID- 25764221
TI  - A matter of access. Nucleosome disassembly from gene promoters is the central
      goal of transcriptional activators.
AB  - The mechanism whereby transcriptional activators facilitate transcription
      activation has been debated. Our recent genome-wide profiling of gene expression
      during aging, where nucleosomes are depleted, indicates that the function of
      seemingly all transcriptional activators is to trigger nucleosome disassembly
      from promoters to allow the general transcription machinery access to the DNA. 

PMID- 25764223
TI  - Investigation, expression, and molecular modeling of ORF2, a metagenomic
      lipolytic enzyme.
AB  - One clone exhibiting lipolytic activity was selected among 30 positives from a
      metagenomic library of a microbe consortium specialized in petroleum hydrocarbon
      degradation. From this clone, a sublibrary was constructed and a metagenome
      contig was assembled and analyzed using the ORF Finder; thus, it was possible to
      identify a potential ORF that encodes a lipolytic enzyme, denoted ORF2. This ORF
      is composed of 1035-bp 345 amino acids and displayed 98 % identity with an
      alpha/beta hydrolase from Pseudomonas nitroreducens (accession number
      WP024765380.1). When analyzed against a metagenome database, ORF2 also showed 76
      % of sequence identity with a hypothetical protein from a marine metagenome
      (accession number ECT55726.1). The ProtParam analyses indicated that the
      recombinant protein ORF2 has a molecular mass approximately 39 kDa, as expected
      from its amino acid sequence, and based on phylogenetic analysis and molecular
      modeling, it was possible to suggest that ORF2 is a new member from family V.
      This enzyme exhibits the catalytic triad and conserved motifs typical from this
      family, wherein the serine residue is located in the central position of the
      conserved motif GASMGG. The orf2 gene was cloned in the expression vector pET28a,
      and the recombinant protein was superexpressed in Escherichia coli BL21(DE3)
      cells. The lipolytic activity of protein bands presented in a SDS-PAGE gel was
      confirmed by zymogram analyses, indicating ORF2 activity. These discoveries raise
      the possibility of employing this protein in biotechnological applications, such
      as bioremediation.

PMID- 25764224
TI  - Modified big-bubble technique compared to manual dissection deep anterior
      lamellar keratoplasty in the treatment of keratoconus.
AB  - PURPOSE: To evaluate the clinical findings and results of manual dissection deep
      anterior lamellar keratoplasty (DALK) compared to a modified big-bubble DALK
      technique in eyes affected by keratoconus. METHODS: Sixty eyes of 60 patients
      with keratoconus were treated with one of the two surgical techniques manual DALK
      (n = 30); big-bubble DALK (n = 30). The main outcomes measured were visual
      acuity, corneal topographic parameters, thickness of residual stroma and
      endothelial cell density (ECD). Patients were examined postoperatively at 1
      month, 6 months, 1 year and 1 month after suture removal. RESULTS: Final best
      spectacle-corrected visual acuity (BSCVA) measured 1 month after suture removal
      was 0.11 +/- 0.08 LogMAR in the big-bubble group compared to 0.13 +/- 0.08 in the
      manual DALK group (p = 0.227). In patients treated with the big-bubble technique
      without complications (Descemet's membrane completely bared), the stromal residue
      was not measureable. Mean stromal residual thickness in the manual DALK group was
      30.50 +/- 27.60 MUm. Data analysis of the manual DALK group demonstrated a
      significant correlation between BSCVA and residual stromal thickness; lower
      residual stromal thickness correlated with better BSCVA values (Spearman rho =
      0.509, p = 0.018). Postoperative ECD was similar in both groups at all intervals,
      with no statistically significant differences. In both groups, ECD loss was only
      significant during the 1- to 6-month interval (p = 0.001 and p < 0.001 in the big
      bubble DALK and manual DALK groups, respectively). CONCLUSION: Manual DALK
      provides comparable results to big-bubble DALK. Big-bubble DALK permits faster
      visual recovery and is a surgical technique, which can be easily converted to
      manual DALK in cases of unsuccessful 'big-bubble' formation.

PMID- 25764226
TI  - Content validity to support the use of a computer-based phonological awareness
      screening and monitoring assessment (Com-PASMA) in the classroom.
AB  - PURPOSE: This study investigated the content validity of a computer-based
      phonological awareness (PA) screening and monitoring assessment (Com-PASMA)
      designed to evaluate school-entry PA abilities. Establishing content validity by
      confirming that test items suitably 'fit' and sample a spectrum of difficulty
      levels is critical for ensuring educators can deduce accurate information to
      comprehensively differentiate curricular reading instruction. METHOD: Ninety-five
      children, inclusive of 21 children with spoken language impairment, participated
      in a 1-year longitudinal study whereby the Com-PASMA was administered at the
      start, middle and end of the school year. RESULT: Estimates of content validity
      using Rasch Model analysis demonstrated that: (1) rhyme oddity and initial
      phoneme identity tasks were most appropriate at school-entry and sampled a
      spectrum of difficulty levels, (2) more challenging phoneme level tasks (e.g.
      final phoneme identity, phoneme blending, phoneme deletion and phoneme
      segmentation) became increasingly appropriate and differentiated between high-
      and low-ability students by the middle and end of the first year of school and
      (3) letter-knowledge tasks were appropriate but declined in their ability to
      differentiate student ability as the year progressed. CONCLUSION: Findings
      demonstrate that the Com-PASMA has sufficient content validity to measure and
      differentiate between the PA abilities of 5-year-old children on entry to school.

PMID- 25764225
TI  - Phosphoproteome characterization reveals that Sendai virus infection activates
      mTOR signaling in human epithelial cells.
AB  - Sendai virus (SeV) is a common respiratory pathogen in mice, rats, and hamsters.
      Host cell recognition of SeV is mediated by pathogen recognition receptors, which
      recognize viral components and induce intracellular signal transduction pathways
      that activate the antiviral innate immune response. Viruses use host proteins to
      control the activities of signaling proteins and their downstream targets, and
      one of the most important host protein modifications regulated by viral infection
      is phosphorylation. In this study, we used phosphoproteomics combined with
      bioinformatics to get a global view of the signaling pathways activated during
      SeV infection in human lung epithelial cells. We identified altogether 1347
      phosphoproteins, and our data shows that SeV infection induces major changes in
      protein phosphorylation affecting the phosphorylation of almost one thousand host
      proteins. Bioinformatics analysis showed that SeV infection activates known
      pathways including MAPK signaling, as well as signaling pathways previously not
      linked to SeV infection including Rho family of GTPases, HIPPO signaling, and
      mammalian target of rapamycin (mTOR)-signaling pathway. Further, we performed
      functional studies with mTOR inhibitors and siRNA approach, which revealed that
      mTOR signaling is needed for both the host IFN response as well as viral protein
      synthesis in SeV-infected human lung epithelial cells. 

PMID- 25764227
TI  - Mechanical performance of spider silk is robust to nutrient-mediated changes in
      protein composition.
AB  - Spider major ampullate (MA) silk is sought after as a biomimetic because of its
      high strength and extensibility. While the secondary structures of MA silk
      proteins (spidroins) influences silk mechanics, structural variations induced by
      spinning processes have additional effects. Silk properties may be induced by
      spiders feeding on diets that vary in certain nutrients, thus providing
      researchers an opportunity to assess the interplay between spidroin chemistry and
      spinning processes on the performance of MA silk. Here, we determined the
      relative influence of spidroin expression and spinning processes on MA silk
      mechanics when Nephila pilipes were fed solutions with or without protein. We
      found that spidroin expression differed across treatments but that its influence
      on mechanics was minimal. Mechanical tests of supercontracted fibers and X-ray
      diffraction analyses revealed that increased alignment in the amorphous region
      and to a lesser extent in the crystalline region led to increased fiber strength
      and extensibility in spiders on protein rich diets. 

PMID- 25764228
TI  - Functioning of the hypothalamic-pituitary-adrenal and growth hormone axes in
      frequently unexplained disorders: results of a population study.
AB  - BACKGROUND: The aim of the study was to test the hypothesis that associations
      with specific stress systems [hypothalamic-pituitary-adrenal (HPA) and growth
      hormone (GH) axes] would increase as the number of unexplained disorders
      increased while accounting for the possible confounding effects of psychosocial
      factors. METHODS: A cross-sectional study identified those reporting chronic
      widespread pain, irritable bowel syndrome, chronic orofacial pain and chronic
      fatigue. Of the 1315 subjects, disorder status was available for 1180 (89.7%), of
      whom 766 (64.9%) reported no disorders, 277 (23.5%) reported one and 137 (11.6%)
      reported two or more. Eighty subjects were sought from each group for assessment
      of HPA (morning 8:00 a.m. and evening 10:00 p.m. saliva, and post-dexamethasone
      serum cortisol levels) and GH [serum insulin-like growth factor 1 (IGF-1) level]
      axis function. Validated questionnaires informed current psychological state.
      RESULTS: Two hundred twenty-seven subjects participated [79 (35%) with no
      disorders, 78 (34%) with one disorder and 70 (31%) with two or more disorders].
      There were no significant associations (p < 0.05) between individual disorders or
      an increasing disorder load with any of the neuroendocrine levels measured:
      saliva/serum cortisol, IGF-1 and dehydroepiandrosterone. Psychosocial factors
      were independently associated with disorders and with an increasing disorder
      load: health anxiety p < 0.01, anxiety p < 0.01, depression p < 0.01, life events
      p = 0.03. CONCLUSION: Although previous studies have shown that stress axis
      function acts to moderate the risk of onset of some of these disorders, the
      present study shows that the degree of dysfunction is not correlated with a
      corresponding increasing load of disorders. The uncertainty surrounding the role
      of these biomarkers in the aetiology of unexplained disorders needs further
      investigation.

PMID- 25764229
TI  - Provision of structured diabetes information encourages activation amongst people
      with diabetes as measured by diabetes care process attainment: the WICKED
      Project.
AB  - BACKGROUND: People with diabetes have better outcomes if they actively
      participate in their care. Patient-focused interventions can be effective in
      activating patients. Yet there is no known trial to evaluate the impact of the
      provision of individualized diabetes-specific information on patient activation
      and diabetes care outcomes. METHODS: In a randomized controlled trial, all people
      (n = 14 559) with diabetes within the local health economy were recruited and
      cluster randomized into two groups with the active group mailed a structured
      personalized report containing information on all nine of their diabetes care
      processes, whereas the control group received standard care. Differences in their
      Failed Process Score (FPS) were compared at three months. RESULTS: At three
      months, the FPS score (1.25 +/- 1.87 vs. 1.35 +/- 1.97, P < 0.01) and the change
      in FPS score (0.48 +/- 1.55 vs. 0.42 +/- 1.49, P < 0.02) were significantly
      better in those mailed a structured personalized report. A dichotomized FPS score
      [good attainment (GA) vs. poorer attainment], was significantly better in those
      mailed (chi2 = 10.0, P < 0.05) and using a binary logistic regression analysis
      adjusting for all demographic factors and the baseline FPS, the relative effect
      of mailing compared with non-mailing on three-month GA category was OR 1.14 (95%
      CI 1.04-1.25, P < 0.01). CONCLUSIONS: Provision of structured and individualized
      information to people with diabetes can positively influence the level of patient
      activation, promote better engagement and open the potential to improve other
      crucial diabetes outcomes.

PMID- 25764230
TI  - Advanced imaging of peripheral nerves.

PMID- 25764231
TI  - Current MR neurography techniques and whole-body MR neurography.
AB  - MR neurography (MRN) techniques continue to evolve, leading to a better
      demonstration of peripheral nerve anatomy and pathology. This article discusses
      various technical perspectives and provides recommendations to obtain the best
      possible high-resolution imaging of the peripheral nerves in various areas of the
      body. We also discuss technical perspectives of whole-body MRN and its potential
      utility. 

PMID- 25764232
TI  - Technical advancements in MR neurography.
AB  - MR neurography (MRN) has evolved to become a clinically useful imaging modality
      for evaluating nerve pathologies. Anatomically, nerves are often surrounded by
      fat and blood vessels, which appear bright on MR images impeding the conspicuity
      of nerve visualization. Additionally, nerves are tortuous and would be preferable
      to visualize in three dimensions for proper diagnosis. Various technical
      advancements in the field of MR imaging in general have led to volumetric
      acquisitions with uniform fat and blood suppression. These advancements enabled
      optimized imaging protocols for better visualization of the nerves. This review
      article discusses some of these technical advancements that enabled current MRN
      protocols in routine clinical imaging and certain research techniques that may
      facilitate nerve disorder characterization following interventions. 

PMID- 25764233
TI  - MR neurography: pitfalls in imaging and interpretation.
AB  - MR imaging of peripheral nerves, typically referred to as MR neurography, is a
      rapidly evolving technique that currently is drawing huge attention, both in
      research and in clinical settings. Both training and experience are necessary to
      detect the sometimes subtle findings and to avoid misinterpretation of
      abnormalities. This review article is intended to help radiologists with image
      evaluation and interpretation. Typical pitfalls are discussed as well as
      strategies to avoid them. 

PMID- 25764234
TI  - Neuropathic pain mechanisms and imaging.
AB  - Molecular and cellular imaging of neuropathic pain, utilizing the myriad of
      receptors and inflammatory mediators involved in nociceptive activity, is a
      promising approach toward objectively identifying peripheral pain generators.
      Neuropathic conditions arise from injured and inflamed nerves, which have been
      shown to elaborate several molecular and cellular elements that give rise to the
      neuropathic phenotype and can be exploited for imaging purposes. As such, in vivo
      approaches to image neuropathic pain mechanisms include imaging voltage-gated
      sodium channels with radiolabeled saxitoxin, calcium signaling with manganese
      enhanced magnetic resonance imaging, and inflammatory changes and nerve
      metabolism with (18)F-fluorodeoxyglucose. Imaging approaches exploiting other
      mediators of nociceptive activity, such as substance P (neurokinin-1) receptor,
      sigma-1 receptor, and macrophages, have shown promising early advances in animal
      models. By combining the sensitivity and specificity of molecular imaging with
      the high anatomical, spatial and contrast resolution afforded by computed
      tomography and MRI, radiologists can potentially identify sites of nerve injury
      or neuroinflammation that are implicated as peripheral pain drivers with greater
      accuracy and confidence. In addition to guiding therapy, these approaches will
      aid in new drug designs for analgesia and more individualized treatment options. 

PMID- 25764235
TI  - Neurophysiology simplified for imagers.
AB  - Electrodiagnostic studies are powerful diagnostic tools that complement the
      clinical evaluation of patients with neuromuscular disease. However, their proper
      interpretation requires a hypothesis-driven approach that depends on clinical
      information and physical examination findings. In principle, Bayesian methods of
      reasoning determine both the plan of examination and interpretation of results.
      Thus neuromuscular disease training with an understanding of peripheral nervous
      system anatomy, nerve and muscle physiology, pathophysiology, pathology,
      management, and prognosis are as important as technical training for performance
      of the test. In this article, geared toward imagers, we review the basic
      principles of electrodiagnostic studies, typical measurements, and their
      interpretation both in normal and common disease states. 

PMID- 25764236
TI  - Peripheral neuropathy: surgical approaches simplified for the imagers.
AB  - Peripheral nerves traverse through different soft tissue compartments in the
      upper and lower extremities via specific anatomical tunnels, where they are
      susceptible to entrapment. Common sites in the upper extremity include carpal
      tunnel, cubital tunnel and radial tunnel. Common sites in the lower extremity
      include piriformis, fibular neck, and tarsal tunnel. Compressive peripheral
      neuropathy can develop in these sites, and are amenable for surgical
      decompression. 

PMID- 25764237
TI  - Hereditary and acquired polyneuropathy conditions of the peripheral nerves:
      clinical considerations and MR neurography imaging.
AB  - Polyneuropathies can be classified as either primarily demyelinating or axonal,
      and further as hereditary or acquired. It is important to recognize acquired
      neuropathies because some are amenable to treatment. Clinical findings and
      electrophysiology are used in the routine diagnosis of these conditions. Magnetic
      resonance neurography (MRN) is a helpful supplementary diagnostic tool. This
      article discusses the typical clinical findings, electrophysiology findings, and
      MRN appearances of common hereditary or acquired neuropathies such as chronic
      inflammatory demyelinating neuropathy, multifocal motor neuropathy, diabetic
      neuropathy, chemotherapy-induced neuropathy, and postsurgical neuropathy. 

PMID- 25764238
TI  - Three-dimensional MR imaging of the brachial plexus.
AB  - Pathologic conditions of the brachial plexus often result in serious and
      disabling complications. With the increasing availability and use of new and
      powerful MRI sequences and coils, understanding and assessment of the complex
      anatomy and pathology of the brachial plexus have been greatly facilitated. These
      new technical developments have led to an improved assessment of brachial plexus
      lesions, thereby improving patient care. In this article we describe various MRI
      techniques for the evaluation of the brachial plexus obtained at 1.5 T and 3 T,
      and we explain differences and similarities between sequences and protocols
      performed on MRI equipment from different vendors. The main characteristics of
      pathologic conditions affecting the brachial plexus are discussed and
      illustrated, as well as their differential diagnoses, with an emphasis on key
      imaging findings and relevance for patient management. Pitfalls related to
      suboptimal technique and image interpretation are also addressed. 

PMID- 25764239
TI  - Three-dimensional MR neurography of the lumbosacral plexus.
AB  - The lumbosacral (LS) plexus is a complicated network of nerves, and the complex
      anatomy is resolvable using high-resolution three-dimensional (3D) magnetic
      resonance neurography. This article focuses on 3D imaging evaluation of the
      anatomy and the pathology of various LS plexus branch nerves. 

PMID- 25764240
TI  - High-resolution imaging of upper limb neuropathies.
AB  - MRI of the peripheral nerves continues to grow technologically and in clinical
      use. This article reviews the technological aspects and basic interpretation of
      high-resolution MR imaging of the upper extremity nerves. These techniques work
      with 1.5-, or preferably 3-T, scanners regardless of vendors. The article also
      includes selected pitfalls in the interpretation of upper extremity nerve MRI. 

PMID- 25764241
TI  - Three-dimensional imaging of lower limb neuropathies.
AB  - Peripheral nerve pathology can be detected on high-resolution MRI on the basis of
      primary or secondary findings. Primary findings of nerve pathology include
      alterations in signal, course, and caliber; secondary findings include skeletal
      muscle denervation. Although two-dimensional (2D) MRI sequences comprised of a
      combination of fluid-sensitive and non-fat-suppressed anatomical sequences can
      detect changes in nerve size, signal, course, and architecture, three-dimensional
      (3D) imaging can play an important role in the detection and characterization of
      nerve pathology including caliber changes at typical compression sites, anomalous
      course, and nerve discontinuity. This article discusses the benefits of 3D MRI
      with respect to lower limb neuropathies. The article also reviews the normal
      anatomy of the nerves in the lower extremity from the hip joint to the foot, and
      it illustrates common causes and the imaging appearance of lower limb peripheral
      neuropathy. 

PMID- 25764242
TI  - Advanced MR imaging of peripheral nerve sheath tumors including diffusion
      imaging.
AB  - Peripheral nerve sheath tumors (PNSTs) are neoplasms derived from neoplastic
      Schwann cells or their precursors. Whereas benign PNSTs are relatively common and
      considered curable lesions, their malignant counterparts are rare but highly
      aggressive and require early diagnosis and treatment. MR imaging has been the
      modality of choice for noninvasive evaluation of PNSTs. This article discusses
      the features of PNSTs in conventional and advanced MR imaging, and it emphasizes
      the features that help differentiate benign and malignant variants. 

PMID- 25764243
TI  - Diffusion tensor imaging of peripheral nerves.
AB  - Diffusion tensor imaging (DTI) is a powerful MR imaging technique that can be
      used to probe the microstructural environment of highly anisotropic tissues such
      as peripheral nerves. DTI has been used predominantly in the central nervous
      system, and its application in the peripheral nervous system does pose some
      challenges related to imaging artifacts, the small caliber of peripheral nerves,
      and low water proton density. However advances in MRI hardware and software have
      made it possible to use the technique in the peripheral nervous system and to
      obtain functional data relating to the effect of pathologic processes on
      peripheral nerves. This article reviews the imaging principles behind DTI and
      examines the literature regarding its application in assessing peripheral nerves.

PMID- 25764244
TI  - Characterization and Comparison of Protein and Peptide Profiles and their
      Biological Activities of Improved Common Bean Cultivars (Phaseolus vulgaris L.)
      from Mexico and Brazil.
AB  - Common bean (Phaseolus vulgaris L.) is a good source of protein, vitamins,
      minerals and complex carbohydrates. The objective was to compare protein profile,
      including anti-nutrient proteins, and potential bioactive peptides of improved
      common bean cultivars grown in Mexico and Brazil. Bean protein isolates (BPI)
      were prepared from 15 common bean cultivars and hydrolyzed using
      pepsin/pancreatin. Thirteen proteins were identified by SDS-PAGE and protein in
      gel tryptic-digestion-LC/MS. Protein profile was similar among common bean
      cultivars with high concentrations of defense-related proteins. Major identified
      proteins were phaseolin, lectin, protease and alpha-amylase inhibitors. Lectin
      (159.2 to 357.9 mg lectin/g BPI), Kunitz trypsin inhibitor (inh) (4.3 to 75.5 mg
      trypsin inh/g BPI), Bowman-Birk inhibitor (5.4 to 14.3 MUg trypsin-chymotrypsin
      inh/g BPI) and alpha-amylase inhibitor activity (2.5 to 14.9% inhibition relative
      to acarbose/mg BPI) were higher in Mexican beans compared to Brazilian beans.
      Abundant peptides were identified by HPLC-MS/MS with molecular masses ranging
      from 300 to 1500 Da and significant sequences were SGAM, DSSG, LLAH, YVAT, EPTE
      and KPKL. Potential bioactivities of sequenced peptides were angiotensin
      converting enzyme inhibitor (ACE), dipeptidyl peptidase IV inhibitor (DPP-IV) and
      antioxidant capacity. Peptides from common bean proteins presented potential
      biological activities related to control of hypertension and type-2 diabetes.

PMID- 25764245
TI  - Impact of flattening-filter-free radiation on the clonogenic survival of
      astrocytic cell lines.
AB  - BACKGROUND AND PURPOSE: Flattening-filter-free (FFF) beams are increasingly used
      in radiotherapy as delivery times can be substantially reduced. However, the
      relative biologic effectiveness (RBE) of FFF may be increased relative to
      conventional flattened (FLAT) beams due to differences in energy spectra.
      Therefore, we investigated the effects of FFF and FLAT beams on the clonogenic
      survival of astrocytoma cells. MATERIAL AND METHODS: Three cell lines (U251, U251
      MGMT, and U87) were irradiated with 6-MV and 10-MV X-rays from a linear
      accelerator in FFF- or FLAT-beam modes at dose rates in the range of 0.5-24
      Gy/min. The surviving fraction (SF) as function of dose (2-12 Gy) was determined
      by the colony formation assay and fitted by the linear-quadratic model. For both
      beams (FFF or FLAT), the cells were pelleted in conical 15-ml centrifuge tubes
      and irradiated at 2-cm depth in a 1 * 1-cm(2) area on the central axis of a 30 *
      30-cm(2) field. Dosimetry was performed with a 0.3-cm(3) rigid ionization
      chamber. RBE was determined for FFF versus FLAT irradiation. RESULTS: The RBE of
      FFF at 7.3-11.3 Gy was 1.027 +/- 0.013 and 1.063 +/- 0.018 relative to FLAT beams
      for 6- and 10-MV beams, respectively, and was only significantly higher than 1
      for 10 MV. Significantly increased survival rates were seen for lower dose rates
      (0.5 Gy/min FLAT vs. 5 Gy/min FLAT) at higher doses (11.9 Gy), while no
      differences were seen at dose rates  >= 1.4 Gy/min (1.4 Gy/min FFF vs. 14 Gy/min
      FFF and 2.4 Gy/min FFF vs. 24 Gy/min FFF). CONCLUSIONS: FFF beams showed only a
      slightly increased RBE relative to FLAT beams in this experimental set-up, which
      is unlikely to result in clinically relevant differences in outcome.

PMID- 25764246
TI  - Infection of the brown alga Ectocarpus siliculosus by the oomycete Eurychasma
      dicksonii induces oxidative stress and halogen metabolism.
AB  - Pathogens are increasingly being recognized as key evolutionary and ecological
      drivers in marine ecosystems. Defence mechanisms of seaweeds, however, have
      mostly been investigated by mimicking infection using elicitors. We have
      established an experimental pathosystem between the genome brown model seaweed
      Ectocarpus siliculosus and the oomycete Eurychasma dicksonii as a powerful new
      tool to investigate algal responses to infection. Using proteomics, we identified
      21 algal proteins differentially accumulated in response to Eu. dicksonii
      infection. These include classical algal stress response proteins such as a
      manganese superoxide dismutase, heat shock proteins 70 and a vanadium
      bromoperoxidase. Transcriptional profiling by qPCR confirmed the induction of the
      latter during infection. The accumulation of hydrogen peroxide was observed at
      different infection stages via histochemical staining. Inhibitor studies
      confirmed that the main source of hydrogen peroxide is superoxide converted by
      superoxide dismutase. Our data give an unprecedented global overview of brown
      algal responses to pathogen infection, and highlight the importance of oxidative
      stress and halogen metabolism in these interactions. This suggests overlapping
      defence pathways with herbivores and abiotic stresses. We also identify
      previously unreported actors, in particular a Rad23 and a plastid-lipid
      associated protein, providing novel insights into the infection and defence
      processes in brown algae. 

PMID- 25764247
TI  - Digital PCR validates 8q dosage as prognostic tool in uveal melanoma.
AB  - BACKGROUND: Uveal melanoma (UM) development and progression is correlated with
      specific molecular changes. Recurrent mutations in GNAQ and GNA11 initiate UM
      development while tumour progression is correlated with monosomy of chromosome 3
      and gain of chromosome 8q. Hence, molecular analysis of UM is useful for
      diagnosis and prognosis. The aim of this study is to evaluate the use of digital
      PCR (dPCR) for molecular analysis of UM. METHODS: A series of 66 UM was analysed
      with dPCR for three hotspot mutations in GNAQ/GNA11 with mutation specific
      probes. The status of chromosomes 3 and 8 were analysed with genomic probes. The
      results of dPCR analysis were cross-validated with Sanger sequencing, SNP array
      analysis, and karyotyping. RESULTS: Using dPCR, we were able to reconstitute the
      molecular profile of 66 enucleated UM. With digital PCR, GNAQ/GNA11 mutations
      were detected in 60 of the 66 UM. Sanger sequencing revealed three rare variants,
      and, combined, these assays revealed GNAQ/GNA11 mutations in 95% of UM. Monosomy
      3 was present in 43 and chromosome 8 aberrations in 52 of the 66 UM. Survival
      analysis showed that increasing 8q copy numbers were positively correlated with
      metastasis risk. CONCLUSION: Molecular analysis with dPCR is fast and sensitive.
      Just like the recurrent genomic aberrations of chromosome 3 and 8, hotspot
      mutations in GNAQ and GNA11 are effectively detected in heterogeneous samples.
      Increased sensitivity contributes to the number of mutations and chromosomal
      aberrations detected. Moreover, quantification of copy number with dPCR validated
      8q dosage as a sensitive prognostic tool in UM, of which implementation in
      disease prediction models will further improve prognostication.

PMID- 25764248
TI  - Results of an open-access lung cancer screening program with low-dose computed
      tomography: the Gdansk experience.
AB  - INTRODUCTION: Lung cancer screening with low-dose computed tomography (LDCT) is
      one of the most promising tools for reducing mortality from lung cancer.
      OBJECTIVES: The aim of the study was to evaluate the results of an open-access
      lung cancer screening program with LDCT. PATIENTS AND METHODS: In total, 8649
      asymptomatic volunteers between 50 and 75 years of age with a smoking history of
      at least 20 pack-years underwent LDCT screening. The presence of lung nodules
      with a diameter of less than 5 mm required a follow-up control visit after 12
      months, and with a diameter of 5 to 10 mm--after 3, 6, and 12 months. Patients
      with a nodule of more than 10 mm in diameter required further diagnostic workup.
      RESULTS: Lung nodules were detected in 4694 individuals (54%). Lung cancer was
      diagnosed in 107 patients (1.24%). Of 8649 participants, 300 (3.5%) were referred
      for further diagnostic workup, and 125 (1.5%) underwent surgical resection (81
      because of malignant lesions; 44, benign lesions). Eighty-one participants (75%)
      underwent surgery with a curative intent, and 26 participants underwent
      oncological treatment. There were no perioperative deaths. The majority of
      surgical patients underwent lobectomy (video-assisted, in 30 patients; and open,
      in 38 patients). Stage I non-small cell lung cancer was detected in 64 of the
      surgical patients (79%). CONCLUSIONS: The detection rate of lung cancer in the
      screening program with low-dose computed tomography is relatively low but
      patients were diagnosed at a very early stage of the disease compared with
      standard clinical practice.

PMID- 25764249
TI  - Estimating vaccine coverage from serial trivariate serologic data in the presence
      of waning immunity.
AB  - INTRODUCTION: Vaccine coverage data are typically collected through vaccine
      registers and retrospective surveys. Alternatively, cross-sectional serosurveys
      enable direct estimation of vaccine coverage from antibody prevalence by
      exploiting correlated seropositivity for multi-antigen vaccines. Here, we extend
      previous methods by accounting for temporal antibody decline in estimating
      vaccine coverage for measles-mumps-rubella vaccine using serial serosurvey data.
      METHODS: We introduce a Markovian cohort model of antibody waning and boosting
      applied to dichotomous seropositivity data for measles, mumps, and rubella.
      Simulation studies are used to test model identifiability and to explore bias
      induced by previous methods that ignore waning. The cohort model is then fitted
      to three Australian serosurveys, entailing estimates of vaccine coverage from
      routine and catch-up vaccination as well as waning rates for each antigen.
      RESULTS: The simulation results show that the cohort model is identifiable and
      qualitatively captures the decline in seropositivity observed in older children.
      When fitted to all three Australian surveys, the estimated seroconversion and
      waning parameters are similar to estimates based on recent meta-analyses, whereas
      the coverage estimates appear consistent with previous Australian survey-based
      estimates. DISCUSSION: We show that previous methods of estimating coverage from
      serological data can be improved by fitting a cohort model with waning and
      boosting processes to serial serosurvey data, furthermore yielding estimates of
      more parameters of interest such as rates of waning. In settings where serial
      serosurvey data is available, our method could be duplicated or applied to
      related questions such as coverage in routine two-dose schedules or from other
      combination vaccines.

PMID- 25764250
TI  - Commentary: Cohort studies of the efficacy of screening for cancer.

PMID- 25764251
TI  - The urgent need for a systems biology approach to neurology.

PMID- 25764252
TI  - Neurophotonics: non-invasive optical techniques for monitoring brain functions.
AB  - The aim of this review is to present the state of the art of neurophotonics, a
      recently founded discipline lying at the interface between optics and
      neuroscience. While neurophotonics also includes invasive techniques for animal
      studies, in this review we focus only on the non-invasive methods that use near
      infrared light to probe functional activity in the brain, namely the fast optical
      signal, diffuse correlation spectroscopy, and functional near infrared
      spectroscopy methods. We also present an overview of the physical principles of
      light propagation in biological tissues, and of the main physiological sources of
      signal. Finally, we discuss the open issues in models, instrumentation, data
      analysis and clinical approaches. 

PMID- 25764253
TI  - Neuroimaging-based methods for autism identification: a possible translational
      application?
AB  - Classification methods based on machine learning (ML) techniques are becoming
      widespread analysis tools in neuroimaging studies. They have the potential to
      enhance the diagnostic power of brain data, by assigning a predictive index,
      either of pathology or of treatment response, to the single subject's
      acquisition. ML techniques are currently finding numerous applications in
      psychiatric illness, in addition to the widely studied neurodegenerative
      diseases. In this review we give a comprehensive account of the use of
      classification techniques applied to structural magnetic resonance images in
      autism spectrum disorders (ASDs). Understanding of these highly heterogeneous
      neurodevelopmental diseases could greatly benefit from additional descriptors of
      pathology and predictive indices extracted directly from brain data. A
      perspective is also provided on the future developments necessary to translate ML
      methods from the field of ASD research into the clinic. 

PMID- 25764254
TI  - Magnetoencephalography in the study of brain dynamics.
AB  - To progress toward understanding of the mechanisms underlying the functional
      organization of the human brain, either a bottom-up or a top-down approach may be
      adopted. The former starts from the study of the detailed functioning of a small
      number of neuronal assemblies, while the latter tries to decode brain functioning
      by considering the brain as a whole. This review discusses the top-down approach
      and the use of magnetoencephalography (MEG) to describe global brain properties.
      The main idea behind this approach is that the concurrence of several areas is
      required for the brain to instantiate a specific behavior/functioning. A central
      issue is therefore the study of brain functional connectivity and the concept of
      brain networks as ensembles of distant brain areas that preferentially exchange
      information. Importantly, the human brain is a dynamic device, and MEG is ideally
      suited to investigate phenomena on behaviorally relevant timescales, also
      offering the possibility of capturing behaviorally-related brain connectivity
      dynamics. 

PMID- 25764256
TI  - Excitability of spinal neural function during motor imagery in Parkinson's
      disease.
AB  - the median nerve at the wrist in subjects during two motor imagery conditions:
      holding and not holding the sensor of a pinch meter between the thumb and index
      finger. Our aim was to determine whether mental simulation without the muscle
      contraction associated with motion can increase the excitability of spinal neural
      function in patients with Parkinson's disease (PD). F-waves of the left thenar
      muscles were examined in 10 patients with PD under resting, holding and motor
      imagery conditions. For the holding condition, the subjects held the sensor of
      the pinch meter between their thumb and index finger. For the motor imagery
      conditions, the subjects were asked to imagine a 50% maximal voluntary isometric
      contraction holding and not holding the sensor of the pinch meter between their
      thumb and index finger (motor imagery "with"/"without sensor"). Persistence
      during motor imagery under the "with sensor" condition increased significantly
      compared with persistence during resting (n=10, z=2.2509, p=0.0244, Wilcoxon
      test). The F/M amplitude ratio during motor imagery under the "with sensor"
      condition increased significantly compared with that during resting (n=10,
      z=2.1915, p=0.0284, Wilcoxon test). Excitability of spinal neural function during
      motor imagery in Parkinson's disease Motor imagery under the "with the sensor"
      condition increased excitability of the spinal neural output to the thenar
      muscles. Because excitability of the spinal neural output to the thenar muscles
      during motor imagery "with the sensor" was significantly higher than that during
      resting, we suggest that movement preparation for a motor imagery task is
      important in patients with PD. 

PMID- 25764255
TI  - Assessing and restoring cognitive functions early after stroke.
AB  - Cognitive impairment is a frequent complication of stroke. The aim of this study
      was to evaluate the effectiveness of cognitive training performed early after
      stroke. Ninety-two patients were randomly assigned to either the study group (SG)
      or the control group (CG). Cognitive rehabilitation consisted of 16 individual
      one-hour sessions in which patients performed therapist- guided computer
      exercises. The patients in the CG performed a sham intervention. After four weeks
      all the patients were re-evaluated. In the SG, significant improvements (p<0.05)
      were detected in all neuropsychological measures at the post-training evaluation,
      while the CG showed mild (not statistically significant) improvements on
      cognitive tests. Between-group analysis revealed statistically significant
      differences in the domains of memory and visual attention. Cognitive training
      performed early after stroke seems to be a viable option for improving cognitive
      outcome in stroke survivors. Further studies should assess whether this may favor
      their reintegration into everyday life.

PMID- 25764257
TI  - Co-occurrence of multiple sclerosis and Thomsen's myotonia: a report of two
      cases.
AB  - Multiple sclerosis (MS) is a common demyelinating disease of the central nervous
      system in which an abnormal immune system response results in damage to the
      myelin sheaths surrounding nerves. The etiology of MS remains elusive, although
      it has been suggested to be influenced by both genetic and environmental factors.
      Here, we report two exceptional cases of patients affected by both MS and
      Thomsen's myotonia. Electromyography and MRI scans confirmed the presence of both
      diseases in the referred cases. Although the mechanisms underlying the co
      occurrence of MS and Thomsen's disease are unclear, we have endeavored to offer
      plausible explanations for it. 

PMID- 25764258
TI  - Effect of cranioplasty on functional and neuro - psychological recovery after
      severe acquired brain injury: fact or fake? Considerations on a single case.
AB  - Cranioplasty is performed, using autograft materials, to treat the "trephined
      syndrome" in patients previously submitted to craniectomy. Indeed, considerable
      improvements in neuropsychological deficits, control of convulsions and partial
      prevention of cerebral atrophy are achieved after this surgical procedure. We
      describe the pre- and post-operative neuropsychological and functional evaluation
      of a 30-year-old male patient who underwent cranioplasty following previous
      craniectomy for a subarachnoid hemorrhage due to a spontaneously ruptured
      aneurysm of the right middle cerebral artery. 

PMID- 25764259
TI  - Paraneoplastic cerebellar ataxia associated with anti-Hu antibodies and benign
      ganglioneuroma.
AB  - We describe a case of cerebellar ataxia associated with anti-Hu antibodies and
      benign ganglioneuroma. A 28-year-old woman developed progressive ataxia with
      hyporeflexia at the age of 19. Brain MRI showed progressive cerebellar atrophy.
      Neurophysiological studies, screening of immune-mediated ataxias, oncological
      markers, vitamin E and genetic tests for spinocerebellar ataxia types 1,2,3,
      Friedreich ataxia and POLG1 were negative. Anti-Hu antibodies were positive in
      Western blot and indirect immunofluorescence (1:640). Total-body computed
      tomography revealed a mediastinum mass; the histological diagnosis was maturing
      ganglioneuroma. Immunohistochemistry showed a mild reaction between the tumor and
      the patient's serum, and no reaction between the tumor and control serum. After
      surgery, serum anti-Hu titer decreased, while ataxic symptoms initially worsened
      and then stabilized. Ganglioneuroma is a benign tumor, usually derived from the
      maturation of a neuroblastoma. The benign histology and the presence of anti-Hu
      antibodies could be related to the positive oncological prognosis and to the slow
      clinical course mimicking a degenerative ataxia.

PMID- 25764260
TI  - Takotsubo syndrome: consequence or cause of ischemic stroke.

PMID- 25764261
TI  - Authors' reply to Finsterer and Aliyev.

PMID- 25764262
TI  - Reticular pseudodrusen associated with a diseased bruch membrane in
      pseudoxanthoma elasticum.
AB  - IMPORTANCE: Reticular pseudodrusen (RPD) are frequently associated with age
      related macular degeneration and considered to be an independent risk factor for
      disease progression, but the pathophysiologic mechanisms are only incompletely
      understood. Therefore, it may be helpful to identify the associations of RPD with
      other diseases that have defined pathophysiologic mechanisms. OBJECTIVE: To
      describe the phenotype, prevalence, and topographic distribution of RPD in
      patients with pseudoxanthoma elasticum (PXE) and their association with a
      diseased Bruch membrane. DESIGN, SETTING, AND PARTICIPANTS: In this single
      center, prospective, cross-sectional case series, 57 consecutive patients with
      PXE from a university referral center whose diagnosis has been confirmed by
      genetic testing and/or skin biopsy were studied from March 1, 2013, through
      February 28, 2014. MAIN OUTCOMES AND MEASURES: Phenotypic characteristics of RPD
      were evaluated with multiple imaging techniques. The RPD were defined as
      irregular networks of round to oval lesions that appear hyporeflective on near
      infrared reflectance, hypoautofluorescent on fundus autofluorescence, and as
      subretinal deposits on spectral-domain optical coherence tomographic images. The
      presence of RPD was judged based on characteristic findings in at least 2 of the
      3 imaging modalities. RESULTS: A total of 57 patients were examined, and 15
      patients were excluded mainly because of large central atrophy or fibrosis. In
      the remaining 42 patients with PXE, RPD were detected in 22 patients (52%; 95%
      CI, 38%-67%). Prevalence of RPD was highest in the fifth decade at 67% (10/15;
      95% CI, 42%-85%). The RPD were most frequently located within the superior
      quadrant and least frequently located within the central macula. The RPD were
      always located central to areas with peau d'orange and within an area of
      hypofluorescence on late-phase indocyanine green angiographic images. CONCLUSIONS
      AND RELEVANCE: These data suggest that RPD have a high prevalence in eyes of
      patients with PXE. Although RPD in patients with PXE occur at a younger age,
      their distribution and phenotype appear to be similar to RPD associated with age
      related macular degeneration. The association with diseased Bruch membrane in PXE
      suggests a pathogenetic role of Bruch membrane alterations for the development of
      RPD.

PMID- 25764263
TI  - The relationship of physicochemical properties to the antioxidative activity of
      free amino acids in Fenton system.
AB  - Herein we compared antioxidative activities (AA) of 25 free L-amino acids (FAA)
      against Fenton system-mediated hydroxyl radical (HO(*)) production in aqueous
      solution, and examined the relation between AA and a set of physicochemical
      properties. The rank order according to AA was: Trp > norleucine > Phe, Leu > Ile
      > His >3,4-dihydroxyphenylalanine, Arg > Val > Lys, Tyr, Pro > hydroxyproline >
      alpha-aminobutyric acid > Gln, Thr, Ser > Glu, Ala, Gly, Asn, Asp. Sulfur
      containing FAA generated different secondary reactive products, which were
      discriminated by the means of electron paramagnetic resonance spin-trapping
      spectroscopy. AA showed a general positive correlation with hydrophobicity.
      However, when taken separately, uncharged FAA exhibited strong positive
      correlation of AA with hydrophobicity whereas charged FAA showed negative or no
      significant correlation depending on the scale applied. A general strong negative
      correlation was found between AA and polarity. Steric parameters and hydration
      numbers correlated positively with AA of nonpolar side-chain FAA. In addition, a
      decrease of temperature which promotes hydrophobic hydration resulted in
      increased AA. This implies that HO(*)-provoked oxidation of FAA is strongly
      affected by hydrophobic hydration. Our findings are important for the
      understanding of oxidation processes in natural and waste waters.

PMID- 25764264
TI  - Orthostatic hypotension in Parkinsonism: What is it and how can we treat it?

PMID- 25764265
TI  - Ruthenium-catalyzed heteroatom-directed regioselective C-H arylation of indoles
      using a removable tether.
AB  - A new approach to C-2 arylated indoles has been developed by utilizing a
      ruthenium-catalyzed, heteroatom-directed regioselective C-H arylation. The
      reaction is highly site-selective and results in very good yields. The highlight
      of the work is the use of a removable directing group and compatibility of the
      catalytic system with halogen functional groups in the substrates. 

PMID- 25764266
TI  - Utilizing Telehealth to Support Treatment of Acute Stress Disorder in a Theater
      of War: Prolonged Exposure via Clinical Videoconferencing.
AB  - BACKGROUND: Posttraumatic stress disorder (PTSD) and acute stress disorder are
      prevalent mental health diagnoses associated with the military operations in Iraq
      and Afghanistan and are especially significant in service members returning from
      combat. Prolonged exposure (PE) therapy is a highly effective behavioral
      treatment for these symptoms, and providing this treatment as soon as possible,
      even in the midst of a soldier's combat deployment, has strong potential
      benefits. MATERIALS AND METHODS: In the current case study, telehealth technology
      was used to support the delivery of PE therapy to treat a service member
      diagnosed with acute stress disorder in a war zone. PE was conducted face-to-face
      on the relatively secure Forward Operating Base for the first half of therapy and
      via clinical videoconferencing (CV) to the service member's remote combat outpost
      during the later stages of therapy. The service member exhibited marked
      improvements in symptoms over 10 sessions. RESULTS: Results are consistent with
      previous empirical findings and highlight the potential benefits of using
      telehealth to deliver evidenced-based treatment for traumatic stress disorders in
      a war zone. This case study provides a preliminary working model for delivering
      PE in a combat environment using multiple delivery systems. CONCLUSIONS: Benefits
      and clinical utility of CV-delivered exposure therapy are discussed, particularly
      for providers pending future operational deployments (e.g., including members of
      the military, independent government agencies, and first responders) and for
      those treating patients in remote locations.

PMID- 25764267
TI  - Correction: sperm morphology in two house mouse subspecies: do wild-derived
      strains and wild mice tell the same story?

PMID- 25764268
TI  - Antioxidant and anti-inflammatory properties of an aqueous cyanophyta extract
      derived from Arthrospira platensis: contribution to bioactivities by the non
      phycocyanin aqueous fraction.
AB  - The goal for this work was to characterize basic biological properties of a novel
      Arthrospira platensis-based aqueous cyanophyta extract (ACE), enriched in the
      known anti-inflammatory cyclooxygenase-2 (COX-2) inhibitor phycocyanin (PC), but
      also containing a high level of non-PC bioactive compounds. Antioxidant
      properties were tested in parallel in the Folin-Ciocalteu assay (chemical
      antioxidant capacity) and in the cellular antioxidant protection (CAP-e)
      bioassay, where both the PC and the non-PC fractions contributed to the
      antioxidant capacity and CAP of ACE. In contrast to the COX-2 inhibition seen in
      the presence of PC, the inhibition of enzymatic activity of the inflammatory
      mediator Lipoxygenase was associated specifically with the non-PC fraction of
      ACE. Inhibition of formation of reactive oxygen species (ROS) was evaluated using
      polymorphonuclear cells from healthy human donors. The inhibition of ROS
      formation was seen for both the PC and non-PC fractions, with ACE showing the
      most robust effect. The effects of PC, non-PC, and ACE on clotting and clot
      lysing was tested using a modified Euglobulin fibrinolytic assay in vitro. In the
      presence of PC, non-PC, and ACE, the time for clot formation and lysis was not
      affected; however, the clots were significantly more robust. This effect was
      statistically significant (p<.05) at doses between 125-500 MUg/mL, and returned
      to baseline at lower doses. Both PC and the non-PC fraction contributed to the
      antioxidant properties and anti-inflammatory effects, without a negative impact
      on blood clotting in vitro. This suggests a potential benefit for the consumable
      ACE extract in assisting the reduction of inflammatory conditions. 

PMID- 25764269
TI  - Link between cell junctions and microtubule cytoskeleton is critical for
      epithelial morphogenesis.

PMID- 25764271
TI  - Erratum.

PMID- 25764270
TI  - Scope of practice and legislation for nurse practitioners in Taiwan.
AB  - PURPOSE: The purpose of the article is to describe the scope of practice
      legislation in Taiwan, with some comparisons to the scope of practice legislation
      in the United States, as well as to identify the issues of nurse practitioner
      (NP) practice. DATA SOURCES: A literature review was conducted to determine the
      limitations of the administrative directives used to govern NP scope of practice.
      A simultaneous review of authoritative resources, including the Ministry of
      Health and Welfare's administrative directives related to NP practice, the
      Physicians Act and Nurses Act of Taiwan, and the statement of the Taiwan
      Association of NPs, was conducted and the documents analyzed. CONCLUSION: Based
      only on administrative directives, and without law and regulations, it was
      difficult to define the scope of practice. It was determined, however, that,
      since the addition of Paragraphs 3 and 4 of Article 23 of the Nurses Act, NPs
      became able to provide a high quality of care legally, which helps to facilitate
      the professionalism of NPs. IMPLICATIONS FOR PRACTICE: Legislation still has a
      long way to go, and through sharing our findings on the NP legislation process,
      we hope to gain the support of NPs around the world and to encourage an
      understanding and the legislation of this new role.

PMID- 25764272
TI  - Treatment summaries, follow-up care instructions, and patient navigation: could
      they be combined to improve cancer survivor's receipt of follow-up care?
AB  - PURPOSE: Cancer survivors require follow-up care to ensure early detection of
      recurrence, management of late/long term effects, preventive screening for early
      detection of second primary malignancies, as well as other forms of preventive
      care. But not all survivors receive necessary follow-up care. Combining
      survivorship care plans and patient navigation may be a successful strategy to
      improve survivor's receipt of necessary follow-up care. METHODS: Using data from
      the 2010 LIVESTRONG online survey of cancer survivors (N = 3854), this study
      tested associations between receipt of follow-up care instructions (FCI) and
      treatment summaries (TS) paired with patient navigation (PN), and survivor's
      receipt of cancer surveillance, preventive cancer screening, and attendance at
      regular medical appointments. RESULTS: Survivors who received FCI, TS, and
      patient navigation were the most likely to report attendance at all medical
      appointments (aOR 4.17, 95% CI 2.30, 7.57, p <= .001) and receipt of preventive
      cancer screening (aOR 3.56, 95% CI 2.28, 5.55, p <= .001). CONCLUSIONS:
      Likelihood of receiving follow-up care was greatest when survivors received FCI,
      TS, and PN. This pairing appeared to be most beneficial for survivor's attendance
      at medical appointments and receipt of preventive cancer screening. IMPLICATIONS
      FOR CANCER SURVIVORS: By improving attendance at medical appointments and
      prevention cancer screening, pairing SCP and PN could benefit survivors through
      reduced recurrence, earlier recurrence detection, and prevention of second
      primaries.

PMID- 25764273
TI  - Impulsivity, Mental Disorder, and Suicide in Rural China.
AB  - The purpose of this study was to investigate the relationship among impulsivity,
      mental disorder, and suicide with a sample of rural young Chinese. Subjects were
      392 consecutively recruited male and female suicides aged 15-34 years and 416
      community male and female controls of the same age range sampled in rural China.
      The case-control data were obtained using psychological autopsy with structured
      and semi-structured instruments. Dysfunctional impulsivity was a significant risk
      factor regardless of mental disorder in rural China. Dysfunctional impulsivity is
      a potential area for further study of suicidal behavior. The suicide prevention
      efforts in rural China may address impulsivity.

PMID- 25764274
TI  - Feasibility of intramolecular proton transfers in terpene biosynthesis--guiding
      principles.
AB  - On the basis of results from quantum chemical calculations, the feasibility of an
      extensive series of intramolecular proton-transfer reactions postulated to occur
      during terpene biosynthesis is assessed and guiding principles are proposed. 

PMID- 25764275
TI  - Aetiology and risk factors of community-acquired pneumonia in hospitalized
      patients in Norway.
AB  - BACKGROUND AND AIMS: In Norway, data on the aetiology of community-acquired
      pneumonia (CAP) in hospitalized patients are limited. The aims of this study were
      to investigate the bacterial aetiology of CAP in hospitalized patients in Norway,
      risk factors for CAP and possible differences in risk factors between patients
      with Legionnaire's disease and pneumonia because of other causes. METHODS: Adult
      patients with radiologically confirmed CAP admitted to hospital were eligible for
      the study. Routine aerobic and Legionella culture of sputum, blood culture,
      urinary antigen test for Legionella pneumophila and Streptococcus pneumoniae,
      polymerase chain reaction detection of Chlamydophila pneumoniae, Mycoplasma
      pneumoniae and Bordetella pertussis from throat specimens, and serology for L.
      pneumophila serogroup 1-6 were performed. A questionnaire, which included
      demographic and clinical data, risk factors and treatment, was completed.
      RESULTS: We included 374 patients through a 20-month study period in 2007-2008.
      The aetiological agent was detected in 37% of cases. S. pneumoniae (20%) was the
      most prevalent agent, followed by Haemophilus influenzae (6%) and Legionella spp.
      (6%). Eight Legionella cases were diagnosed by urinary antigen test, of which
      four also had positive serology. In addition, 13 Legionella cases were diagnosed
      by serology. The degree of comorbidity was high. An increased risk of hospital
      diagnosed Legionella pneumonia was found among patients with a diagnosis of
      chronic congestive heart failure. CONCLUSION: Our results indicate that S.
      pneumoniae is the most common bacterial cause of pneumonia in hospitalized
      patients, and the prevalence of Legionella pneumonia is probably higher in Norway
      than recognized previously.

PMID- 25764276
TI  - CRISPR-Cas Adaptive Immune Systems of the Sulfolobales: Unravelling Their
      Complexity and Diversity.
AB  - The Sulfolobales have provided good model organisms for studying CRISPR-Cas
      systems of the crenarchaeal kingdom of the archaea. These organisms are infected
      by a wide range of exceptional archaea-specific viruses and conjugative plasmids,
      and their CRISPR-Cas systems generally exhibit extensive structural and
      functional diversity. They carry large and multiple CRISPR loci and often
      multiple copies of diverse Type I and Type III interference modules as well as
      more homogeneous adaptation modules. These acidothermophilic organisms have
      recently provided seminal insights into both the adaptation process, the diverse
      modes of interference, and their modes of regulation. The functions of the
      adaptation and interference modules tend to be loosely coupled and the stringency
      of the crRNA-DNA sequence matching during DNA interference is relatively low, in
      contrast to some more streamlined CRISPR-Cas systems of bacteria. Despite this,
      there is evidence for a complex and differential regulation of expression of the
      diverse functional modules in response to viral infection. Recent work also
      supports critical roles for non-core Cas proteins, especially during Type III
      directed interference, and this is consistent with these proteins tending to
      coevolve with core Cas proteins. Various novel aspects of CRISPR-Cas systems of
      the Sulfolobales are considered including an alternative spacer acquisition
      mechanism, reversible spacer acquisition, the formation and significance of
      antisense CRISPR RNAs, and a novel mechanism for avoidance of CRISPR-Cas defense.
      Finally, questions regarding the basis for the complexity, diversity, and
      apparent redundancy, of the intracellular CRISPR-Cas systems are discussed. 

PMID- 25764278
TI  - A Balanced Scorecard With Strategy Map: Measuring the Value of a Nursing
      Sabbatical.
AB  - Seasoned nurses frequently resign from their positions due to burnout. An
      innovative idea that could support nurse retention is nurse sabbaticals. Balanced
      scorecards with strategy maps can display financial benefit, positive customer
      experience, and operational and human capital development required to initiate
      and sustain a professional nurse sabbatical. A balanced scorecard with strategy
      map is an effective tool that demonstrates connection between the organizational
      mission and the outcomes of a nurse sabbatical program. 

PMID- 25764277
TI  - Archaeal Clusters of Orthologous Genes (arCOGs): An Update and Application for
      Analysis of Shared Features between Thermococcales, Methanococcales, and
      Methanobacteriales.
AB  - With the continuously accelerating genome sequencing from diverse groups of
      archaea and bacteria, accurate identification of gene orthology and availability
      of readily expandable clusters of orthologous genes are essential for the
      functional annotation of new genomes. We report an update of the collection of
      archaeal Clusters of Orthologous Genes (arCOGs) to cover, on average, 91% of the
      protein-coding genes in 168 archaeal genomes. The new arCOGs were constructed
      using refined algorithms for orthology identification combined with extensive
      manual curation, including incorporation of the results of several completed and
      ongoing research projects in archaeal genomics. A new level of classification is
      introduced, superclusters that untie two or more arCOGs and more completely
      reflect gene family evolution than individual, disconnected arCOGs. Assessment of
      the current archaeal genome annotation in public databases indicates that
      consistent use of arCOGs can significantly improve the annotation quality. In
      addition to their utility for genome annotation, arCOGs also are a platform for
      phylogenomic analysis. We explore this aspect of arCOGs by performing a
      phylogenomic study of the Thermococci that are traditionally viewed as the basal
      branch of the Euryarchaeota. The results of phylogenomic analysis that involved
      both comparison of multiple phylogenetic trees and a search for putative derived
      shared characters by using phyletic patterns extracted from the arCOGs reveal a
      likely evolutionary relationship between the Thermococci, Methanococci, and
      Methanobacteria. The arCOGs are expected to be instrumental for a comprehensive
      phylogenomic study of the archaea. 

PMID- 25764279
TI  - Myocardial T1 and T2 mapping in diastolic and systolic phase.
AB  - The aim of this study was to evaluate the regional (i.e. myocardial segments)
      variability as well as the overall image quality of cardiac T1 and T2 maps
      obtained in diastole and in systole. In 22 healthy subjects (group-1), diastolic
      T1 and T2 maps were obtained at 1.5 T in short-axis view at basal, mid
      ventricular and apical level, as well as in 4-chamber (4 ch) and in 2-chamber (2
      ch) views. In another group of 25 patients (group-2), the maps were obtained in
      both diastole and systole. In the group-1, 15.4% of myocardial segments in T1
      maps and 0.8% of myocardial segments in T2 maps, mainly located at apical level,
      showed relevant artifacts and/or partial-volume effect and had to be discarded.
      We found no significant difference in T1 values among basal, mid-ventricular and
      apical segments. T2 values at apical level were significantly higher than at
      basal and mid-ventricular level (short-axis, p < 0.0001; 4 ch, p < 0.009; 2 ch, p
      = 0.0002 at ANOVA tests). In the group-2, 21.1%/5.3% and 4.0%/0.8% of segments
      showed relevant artifacts in diastolic/systolic T1 and T2 maps, respectively.
      Apical T2 values were significantly lower in systole than in diastole. In
      systole, there were no significant differences in T1/T2 among basal, mid
      ventricular and apical segments. The overall quality of T1 and T2 maps drops in
      apical segments. This could be problematic when evaluating focal myocardial
      changes. The acquisition in systole increases the number of evaluable segments.

PMID- 25764281
TI  - Synthesis of 2,4-diarylsubstituted-pyridines through a Ru-catalyzed four
      component reaction.
AB  - A ruthenium-catalyzed one-pot synthesis of 2,4-diarylsubstituted pyridines from
      acetophenones, ammonium acetate and DMF under an oxygen atmosphere is described.
      The carbon atom situated at C6 of the pyridine ring comes from the methyl group
      of DMF and the nitrogen atom comes from ammonium acetate. 

PMID- 25764282
TI  - New frontiers for encapsulation in the chemical industry.
AB  - Encapsulation of actives comprises an area of exploration undergoing rapid growth
      in both academic and industrial research settings. Encapsulation processes are
      employed as a part of product synthesis processes for improved efficiency,
      enhanced stability, active ingredient compatibility, increased safety, targeted
      delivery, and novel performance of the end product. Such technical benefits
      enable producers to offer products with increased formulation complexity, access
      new markets, differentiate products, and improve compatibility and stability,
      while meeting consumer demands with improved performance, reduced costs, and new
      actives. In this review, we highlight several emerging academic areas of
      encapsulation that we believe have specific relevance to industrial formulation,
      with a focus on three primary areas: supramolecular encapsulation, aqueous self
      assembled systems, and emulsion-based capsules. The goal of this review is to
      help identify the major challenges facing encapsulation technology adoption in
      the chemical industry, bringing focus and maximizing the potential value of
      ongoing research efforts. 

PMID- 25764280
TI  - Assessment of Intervention Fidelity and Recommendations for Researchers
      Conducting Studies on the Diagnosis and Treatment of Chronic Cough in the Adult:
      CHEST Guideline and Expert Panel Report.
AB  - BACKGROUND: Successful management of chronic cough has varied in the primary
      research studies in the reported literature. One of the potential reasons relates
      to a lack of intervention fidelity to the core elements of the diagnostic and/or
      therapeutic interventions that were meant to be used by the investigators.
      METHODS: We conducted a systematic review to summarize the evidence supporting
      intervention fidelity as an important methodologic consideration in assessing the
      effectiveness of clinical practice guidelines used for the diagnosis and
      management of chronic cough. We developed and used a tool to assess for five
      areas of intervention fidelity. Medline (PubMed), Scopus, and the Cochrane
      Database of Systematic Reviews were searched from January 1998 to May 2014.
      Guideline recommendations and suggestions for those conducting research using
      guidelines or protocols to diagnose and manage chronic cough in the adult were
      developed and voted upon using CHEST Organization methodology. RESULTS: A total
      of 23 studies (17 uncontrolled prospective observational, two randomized
      controlled, and four retrospective observational) met our inclusion criteria.
      These articles included 3,636 patients. Data could not be pooled for meta
      analysis because of heterogeneity. Findings related to the five areas of
      intervention fidelity included three areas primarily related to the provider and
      two primarily related to the patients. In the area of study design, 11 of 23
      studies appeared to be underpinned by a single guideline/protocol; for training
      of providers, two of 23 studies reported training, and zero of 23 reported the
      use of an intervention manual; and for the area of delivery of treatment, when
      assessing the treatment of gastroesophageal reflux disease, three of 23 studies
      appeared consistent with the most recent guideline/protocol referenced by the
      authors. For receipt of treatment, zero of 23 studies mentioned measuring
      concordance of patient-interventionist understanding of the treatment
      recommended, and zero of 23 mentioned measuring enactment of treatment, with
      three of 23 measuring side effects and two of 23 measuring adherence. The overall
      average intervention fidelity score for all 23 studies was poor (20.74 out of
      48). CONCLUSIONS: Only low-quality evidence supports that intervention fidelity
      strategies were used when conducting primary research in diagnosing and managing
      chronic cough in adults. This supports the contention that some of the
      variability in the reporting of patients with unexplained or unresolved chronic
      cough may be due to lack of intervention fidelity. By following the
      recommendations and suggestions in this article, researchers will likely be
      better able to incorporate strategies to address intervention fidelity, thereby
      strengthening the validity and generalizability of their results that provide the
      basis for the development of trustworthy guidelines.

PMID- 25764283
TI  - Modelling larval movement data from individual bioassays.
AB  - We consider modelling the movements of larvae using individual bioassays in which
      data are collected at a high-frequency rate of five observations per second. The
      aim is to characterize the behaviour of the larvae when exposed to attractant and
      repellent compounds. Mixtures of diffusion processes, as well as Hidden Markov
      models, are proposed as models of larval movement. These models account for
      directed and localized movements, and successfully distinguish between the
      behaviour of larvae exposed to attractant and repellent compounds. A simulation
      study illustrates the advantage of using a Hidden Markov model rather than a
      simpler mixture model. Practical aspects of model estimation and inference are
      considered on extensive data collected in a study of novel approaches for the
      management of cabbage root fly.

PMID- 25764284
TI  - Can substituted allenes be highly efficient leaving groups in catalytic
      processes? A computational investigation.
AB  - There is considerable interest presently in the chemistry of allenes. The current
      computational investigation looks into the possibility of using allenes and their
      derivatives as leaving groups. As it is well known, leaving groups are
      significant in catalytic processes for generating the active site. A full quantum
      mechanical study using density functional theory shows that allenes and their
      derivatives can function as excellent leaving groups. Indeed, the calculations
      show that they can be several orders of magnitude more effective than existing
      ligands for this purpose. The modification of second generation Grubbs' catalysts
      with these ligands suggests that the allene ligand cases that would be most
      effective are those having electron withdrawing groups, especially those that
      have the potential for supramolecular interactions between the substituent groups
      in the free state.

PMID- 25764286
TI  - Systematic review and meta-analysis of internal herniation after gastric bypass
      surgery (Br J Surg 2015; 102: 451-460).

PMID- 25764285
TI  - Kernel compositions of glyphosate-tolerant and corn rootworm-protected MON 88017
      sweet corn and insect-protected MON 89034 sweet corn are equivalent to that of
      conventional sweet corn (Zea mays).
AB  - Monsanto Co. has developed two sweet corn hybrids, MON 88017 and MON 89034, that
      contain biotechnology-derived (biotech) traits designed to enhance sustainability
      and improve agronomic practices. MON 88017 confers benefits of glyphosate
      tolerance and protection against corn rootworm. MON 89034 provides protection
      against European corn borer and other lepidopteran insect pests. The purpose of
      this assessment was to compare the kernel compositions of MON 88017 and MON 89034
      sweet corn with that of a conventional control that has a genetic background
      similar to the biotech sweet corn but does not express the biotechnology-derived
      traits. The sweet corn samples were grown at five replicated sites in the United
      States during the 2010 growing season and the conventional hybrid and 17
      reference hybrids were grown concurrently to provide an estimate of natural
      variability for all assessed components. The compositional analysis included
      proximates, fibers, amino acids, sugars, vitamins, minerals, and selected
      metabolites. Results highlighted that MON 88017 and MON 89034 sweet corns were
      compositionally equivalent to the conventional control and that levels of the
      components essential to the desired properties of sweet corn, such as sugars and
      vitamins, were more affected by growing environment than the biotech traits. In
      summary, the benefits of biotech traits can be incorporated into sweet corn with
      no adverse effects on nutritional quality. 

PMID- 25764287
TI  - Randomized clinical trial of defaecatory function after anterior resection for
      rectal cancer with high versus low ligation of the inferior mesenteric artery.
AB  - BACKGROUND: Defaecatory function is often poor after anterior resection.
      Denervation of the neorectum following high ligation of the inferior mesenteric
      artery (IMA) is a possible cause of impaired defaecatory function. The purpose of
      this randomized clinical trial was to clarify whether the level of ligation of
      the IMA in patients with rectal cancer affects defaecatory function. METHODS:
      Between 2008 and 2011, patients who underwent anterior resection for rectal
      cancer were randomized to receive either high or low ligation of the IMA. The
      primary endpoint was to demonstrate the superiority of low ligation in terms of
      defaecatory function. RESULTS: One hundred patients were enrolled in the study;
      51 were randomized to high ligation of the IMA and 49 to low ligation. There were
      no differences between the groups in terms of clinical data, except tumour stage,
      which was more advanced in the high-ligation group (P = 0.046). Nor were there
      any differences in defaecatory function, self-assessment of defaecation, Faecal
      Incontinence Quality of Life scale or continence score between groups at 3 months
      and 1 year. The number of harvested lymph nodes was similar. The rate of
      symptomatic anastomotic leakage was 16 per cent in the high-ligation group and 10
      per cent in the low-ligation group (P = 0.415). CONCLUSION: The level of ligation
      of the IMA in patients with rectal cancer did not affect defaecatory function or
      the incidence of postoperative complications. REGISTRATION NUMBER: NCT00701012
      (http://www.clinicaltrials.gov).

PMID- 25764290
TI  - A thematic analysis of how prisoners overcome suicidality.
AB  - PURPOSE: The purpose of this paper is to explore the perceptions, beliefs and
      abilities that support adult male prisoners in overcoming suicidality.
      DESIGN/METHODOLOGY/APPROACH: Semi-structured interviews were conducted with eight
      male life sentenced prisoners in a Category B prison. Thematic analysis was used
      to analyse the data and interpret how prisoners have overcome suicidality.
      Findings - Five overarching themes were identified; sense of self, presence of
      meaning, connectedness, shift of perspective and re-establishing control. The
      themes were closely interconnected and revealed novel insights into the variables
      that supported prisoners to overcome suicidality. RESEARCH
      LIMITATIONS/IMPLICATIONS: The themes were drawn from a specific prisoner
      population, which may not be representative of the wider prison population.
      Additionally, the sole focus on suicidality may be an oversimplification of self
      destructive behaviours and could have affected the factors identified. PRACTICAL
      IMPLICATIONS: The results highlight the need to refine suicide prevention
      strategies in prisons; in the assessment of suicide risk, the improvement of
      supportive regimes and the development of psychological interventions.
      ORIGINALITY/VALUE: This research is the first to qualitatively examine the
      factors involved in overcoming suicide in adult male prisoners. The research is
      of value to researchers and practitioners alike, as it extends previous research
      in prison populations and suggests avenues for the development of suicide
      prevention strategies.

PMID- 25764291
TI  - Cooking in prison--from crook to cook.
AB  - PURPOSE: The purpose of this paper is to describe and analyse the principle and
      practice of self-catering system in a Danish prison. Self-catering is a
      reflection of the Danish correctional principle of normalisation between prison
      and community life. Unlike some other jurisdiction, issues of control in meal
      preparation are subordinate to prisoners' right to choose and prepare their own
      food. DESIGN/METHODOLOGY/APPROACH: Findings are derived from 13 months of
      ethnographic fieldwork in a Danish maximum security prison for men, including in
      depth interviews with 68 prisoners. FINDINGS: Overall findings showed that
      thinking about meals and their preparation is time consuming for prisoners who
      tend to be positive about the system making connections with their ability to
      exercise responsibility for making healthily choices. The research concludes that
      prisoners' possibility for developing cooking competences during incarceration
      could support prisoners change in social identity from crook to cook.
      ORIGINALITY/VALUE: Food is a fundamental need and the ability to choose what to
      eat and to prepare one's own food should be a right for all people, including
      prisoners. This research shows that Danish prisoners are very pleased about the
      system of self-catering. Most prisoners are concerned about preparing their own
      meals according to their taste and cultural diversity. If the prison offers the
      opportunity to train as a chef during imprisonment it could support the
      prisoner's change in social identity from crook to cook on the outside.

PMID- 25764292
TI  - Working with complex problem behaviors in juvenile institutional care: staff's
      competence, organizational conditions and public value.
AB  - PURPOSE: Institutional staff encounter juveniles with complex problems
      (externalizing and internalizing) which calls for adequate formal
      education/training and professional experience to deliver quality treatment,
      contributing to an effective organization and increasing public value. The
      purpose of this paper is to investigate staff's formal education, professional
      experience and the institutions' organizational strategies providing knowledge
      and clinical training to staff. DESIGN/METHODOLOGY/APPROACH: The study includes
      staff questionnaires from eight wards (n=102). In addition, 39 in-depth
      interviews were conducted with management and staff members. FINDINGS: Results
      show that institutions lack clearly defined target groups, 70 percent of staff
      members lack college education, 30 percent has never been offered education
      within the organization, and the vast majority of staff does not feel competent
      in performing their daily work. Practical implications - The results from this
      study shed light on an overlooked area in institutions, detention centers and
      prison settings, and are important to policy makers and governmental
      organizations responsible for coercive care of juveniles. ORIGINALITY/VALUE:
      Unlike previous studies, treatment and detention organizations are emphasized as
      similar to manufacturing industry and profit organizations, and the results are
      discussed with departure in organizational theory.

PMID- 25764293
TI  - The health of female prisoners in Indonesia.
AB  - PURPOSE: Indonesian law provides prisoners with basic rights, including access to
      education, health care and nutrition. Yet, structural and institutional
      limitations, notably overcrowding and under-resourcing, prohibits penal
      institutions from fulfilling these commitments for female prisoners. The purpose
      of this paper is to explore their health concerns. DESIGN/METHODOLOGY/APPROACH:
      Six prisons and one detention centre were researched, comprising: female
      prisoners (n=69); clinical officers (six); clinic heads (seven); wardens (seven);
      heads of prisons (seven); and a Directorate representative. Data were collected
      through observation, focus group discussions, in-depth interviews and a semi
      structured questionnaire. Raw data were transcribed and analysed thematically,
      adopting the General Principles of Grounded Theory. FINDINGS: Both "formal" and
      "informal" health-coping strategies were dependent upon a range of factors which
      determined access to treatment, medicines and other items procured both inside
      and outside of the prison, as well as referral services. Informal systems of
      support existed for women, especially in regard to pregnancy and raising of
      babies born in detention. Systems that maintain harmony within cell blocks were
      identified as an important informal coping strategy. ORIGINALITY/VALUE: This
      research is important in informing policy and practice. There is a clear need for
      gender-sensitive legislative frameworks, penal policies and prison rules to
      ensure women's needs are addressed. The identified coping strategies were
      considered viable, but do not replace the need for a health system providing
      women prisoners with levels of care as available in the community, including
      commensurate budgeting, personnel, access and referral to more specialised
      external health services.

PMID- 25764294
TI  - Attitude to rehabilitative counselling in southwestern Nigerian prisons.
AB  - PURPOSE: The purpose of this paper was to examine the attitudes of prison inmates
      and warders (prison staff) to rehabilitative counselling and its relationship to
      their prison status on one hand and their educational attainment on the other.
      DESIGN/METHODOLOGY/APPROACH: The study adopts a descriptive survey research
      design. In all 123 prison inmates and 110 warders were selected by stratified
      random sampling from Osogbo prison headquarters, as well as Ilesa and Ile-Ife
      prisons in southwestern Nigeria. Data were collected through a self-constructed
      questionnaire titled "inmate and prison staff attitude to rehabilitation
      counselling". Data collected were analysed using percentages and chi2 statistics.
      FINDINGS: The results showed that the prison inmates and staff possessed positive
      attitude to rehabilitative counselling. No significant difference was found
      between the attitudes of prison inmates and staff members or on the basis of
      their prison statuses. However, the study found a significant relationship
      between the prison inmates' attitude to rehabilitative counselling and their
      educational attainment. Research LIMITATIONS/IMPLICATIONS: Statutory provision
      needs be made for professional rehabilitative counselling in Nigerian prisons in
      contrast to the religious instructions currently being allowed prisoners.
      Educational opportunities should be provided to ensure that the knowledge so
      obtained complements the rehabilitative counselling. Originality/value - This
      paper fulfils an identified need to study the attitude towards rehabilitative
      counselling.

PMID- 25764295
TI  - A silicon-based two-dimensional chalcogenide: growth of Si2Te3 nanoribbons and
      nanoplates.
AB  - We report the synthesis of high-quality single-crystal two-dimensional, layered
      nanostructures of silicon telluride, Si2Te3, in multiple morphologies controlled
      by substrate temperature and Te seeding. Morphologies include nanoribbons formed
      by VLS growth from Te droplets, vertical hexagonal nanoplates through vapor-solid
      crystallographically oriented growth on amorphous oxide substrates, and flat
      hexagonal nanoplates formed through large-area VLS growth in liquid Te pools. We
      show the potential for doping through the choice of substrate and growth
      conditions. Vertical nanoplates grown on sapphire substrates, for example, can
      incorporate a uniform density of Al atoms from the substrate. We also show that
      the material may be modified after synthesis, including both mechanical
      exfoliation (reducing the thickness to as few as five layers) and intercalation
      of metal ions including Li(+) and Mg(2+), which suggests applications in energy
      storage materials. The material exhibits an intense red color corresponding to
      its strong and broad interband absorption extending from the red into the
      infrared. Si2Te3 enjoys chemical and processing compatibility with other silicon
      based material including amorphous SiO2 but is very chemically sensitive to its
      environment, which suggests applications in silicon-based devices ranging from
      fully integrated thermoelectrics to optoelectronics to chemical sensors. 

PMID- 25764296
TI  - An NH moiety is not required for anion binding to amides in aqueous solution.
AB  - Herein, we use a combination of thermodynamic and spectroscopic measurements to
      investigate the interactions of Hofmeister anions with a thermoresponsive
      polymer, poly(N,N-diethylacrylamide) (PDEA). This amide-based polymer does not
      contain an NH moiety in its chemical structure and, thus, can serve as a model to
      test if anions bind to amides in the absence of an NH site. The lower critical
      solution temperature (LCST) of PDEA was measured as a function of the
      concentration for 11 sodium salts in aqueous solutions, and followed a direct
      Hofmeister series for the ability of anions to precipitate the polymer. More
      strongly hydrated anions (CO3(2-), SO4(2-), S2O3(2-), H2PO4(-), F(-), and Cl(-))
      linearly decreased the LCST of the polymer with increasing the salt
      concentration. Weakly hydrated anions (SCN(-), ClO4(-), I(-), NO3(-), and Br(-))
      increased the LCST at lower salt concentrations but salted the polymer out at
      higher salt concentrations. Proton nuclear magnetic resonance (NMR) was used to
      probe the mechanism of the salting-in effect and showed apparent binding between
      weakly hydrated anions (SCN(-) and I(-)) and the alpha protons of the polymer
      backbone. Additional experiments performed by attenuated total reflection Fourier
      transform infrared (ATR-FTIR) spectroscopy found little change in the amide I
      band upon the addition of salt, which is consistent with very limited, if any,
      interactions between the salt ions and the carbonyl moiety of the amide. These
      results support a molecular mechanism for ion-specific effects on proteins and
      model amides that does not specifically require an NH group to interact with the
      anions for the salting-in effect to occur. 

PMID- 25764297
TI  - Palmitic Acid in Early Human Development.
AB  - Palmitic acid (16:0) is a saturated fatty acid present in the diet and
      synthesized endogenously. Although often considered to have adverse effects on
      chronic disease in adults, 16:0 is an essential component of membrane, secretory,
      and transport lipids, with crucial roles in protein palmitoylation and signal
      molecules. At birth, the term infant is 13-15% body fat, with 45-50% 16:0, much
      of which is derived from endogenous synthesis in the fetus. After birth, the
      infant accumulates adipose tissue at high rates, reaching 25% body weight as fat
      by 4-5 months age. Over this time, human milk provides 10% dietary energy as
      16:0, but in unusual triglycerides with 16:0 on the glycerol center carbon. This
      paper reviews the synthesis and oxidation of 16:0 and possible reasons why the
      infant is endowed with large amounts of fat and 16:0. The marked deviations in
      tissues with displacement of 16:0 that can occur in infants fed vegetable oil
      formulas is introduced. Assuming fetal fatty acid synthesis and the unusual
      delivery of 16:0 in human milk evolved to afford survival advantage to the
      neonate, it is timely to question if 16:0 is an essential component of tissue
      lipids whereby both deficiency and excess are detrimental. 

PMID- 25764298
TI  - Changes in physical activity among adults with diabetes: a longitudinal cohort
      study of inactive patients with Type 2 diabetes who become physically active.
AB  - AIMS: To identify the predictors and clinical effects among inactive patients
      with diabetes who become physically active, in the setting of a large integrated
      health system. METHODS: We studied adults with Type 2 diabetes with at least two
      clinic visits between December 2011 and November 2012 who reported being inactive
      at their first visit. The mean (+/-sd) interval between their first and last
      visit was 6.2 (+/-2.3) months. We analysed self-reported moderate-to-vigorous
      physical activity data collected using a structured intake form during routine
      clinical care. RESULTS: The study cohort (N = 6853) had a mean age of 60.2 years;
      51.4% were women and 53.6% were non-white. Nearly two-thirds (62.5%, n = 4280)
      reported remaining physically inactive, while 16.0% reported achieving the
      recommended moderate-to-vigorous physical activity levels (>= 150 min/week) by
      the last visit of the study period. Female gender (odds ratio 0.77, 95% CI 0.67,
      0.88), obesity (BMI 30-34.9 kg/m(2) : odds ratio 0.76, 95% CI 0.60, 0.97; BMI >=
      35 kg/m(2) : odds ratio 0.55, 95% CI 0.42, 0.70), chronic kidney disease (odds
      ratio 0.78, 95% CI 0.65, 0.94) and depression (odds ratio 0.77, 95% CI 0.62,
      0.96) were each independently associated with not achieving the recommended
      moderate-to-vigorous physical activity level, while physician referral to
      lifestyle education was a positive predictor (odds ratio 1.40, 95% CI 1.09,
      1.85). Controlling for baseline differences, patients achieving the recommended
      moderate-to-vigorous physical activity target lost 1.0 kg more weight compared
      with patients remaining inactive (P < 0.001). CONCLUSIONS: Patients with diabetes
      in a real-world clinical setting lost weight after becoming physically active;
      however, nearly two-thirds of patients remained inactive. Novel interventions to
      address physical inactivity in primary care should address barriers faced by
      older patients with medically complex disease.

PMID- 25764299
TI  - The great escape: pathogen versus host.

PMID- 25764300
TI  - Fluorescence Quenching Determination of Uranium (VI) Binding Properties by Two
      Functional Proteins: Acetylcholinesterase (AChE) and Vitellogenin (Vtg).
AB  - The interactions between uranium and two functional proteins (AChE and Vtg) were
      investigated using fluorescence quenching measurements. The combined use of a
      microplate spectrofluorometer and logarithmic additions of uranium into protein
      solutions allowed us to define the fluorescence quenching over a wide range of
      [U]/[Pi] ratios (from 1 to 3235) at physiologically relevant conditions of pH.
      Results showed that fluorescence from the two functional proteins was quenched by
      UO2 (2+). Stoichiometry reactions, fluorescence quenching mechanisms and
      complexing properties of proteins, i.e. binding constants and binding sites
      densities, were determined using classic fluorescence quenching methods and curve
      fitting software (PROSECE). It was demonstrated that in our test conditions, the
      protein complexation by uranium could be simulated by two specific sites (L1 and
      L2). The obtained complexation constant values are log K1 = 5.7 (+/-1.0), log K2
      = 4.9 (+/-1.1); L1 = 83 (+/-2), L2 = 2220 (+/-150) for U(VI) - Vtg and log K1 =
      8.1 (+/-0.9), log K2 = 6.6 (+/-0.5), L1 = 115 (+/-16), L2 = 530 (+/-23) for U(VI)
      AChE (Li is expressed in mol/mol of protein). 

PMID- 25764301
TI  - To plasticity and back again.
AB  - Both the gain and the loss of flexibility in the development of phenotypes have
      led to an increased diversity of physical forms in nematode worms. 

PMID- 25764302
TI  - Nuclear genomic signals of the 'microturbellarian' roots of platyhelminth
      evolutionary innovation.
AB  - Flatworms number among the most diverse invertebrate phyla and represent the most
      biomedically significant branch of the major bilaterian clade Spiralia, but to
      date, deep evolutionary relationships within this group have been studied using
      only a single locus (the rRNA operon), leaving the origins of many key clades
      unclear. In this study, using a survey of genomes and transcriptomes representing
      all free-living flatworm orders, we provide resolution of platyhelminth
      interrelationships based on hundreds of nuclear protein-coding genes, exploring
      phylogenetic signal through concatenation as well as recently developed consensus
      approaches. These analyses robustly support a modern hypothesis of flatworm
      phylogeny, one which emphasizes the primacy of the often-overlooked
      'microturbellarian' groups in understanding the major evolutionary transitions
      within Platyhelminthes: perhaps most notably, we propose a novel scenario for the
      interrelationships between free-living and vertebrate-parasitic flatworms,
      providing new opportunities to shed light on the origins and biological
      consequences of parasitism in these iconic invertebrates. 

PMID- 25764304
TI  - New ways to make a blood cell.
AB  - In a niche under the skin in Drosophila larvae, blood cells called plasmatocytes
      can transform into other classes of blood cell. 

PMID- 25764305
TI  - Good and bad news about Ebola.

PMID- 25764303
TI  - The Ret receptor regulates sensory neuron dendrite growth and integrin mediated
      adhesion.
AB  - Neurons develop highly stereotyped receptive fields by coordinated growth of
      their dendrites. Although cell surface cues play a major role in this process,
      few dendrite specific signals have been identified to date. We conducted an in
      vivo RNAi screen in Drosophila class IV dendritic arborization (C4da) neurons and
      identified the conserved Ret receptor, known to play a role in axon guidance, as
      an important regulator of dendrite development. The loss of Ret results in severe
      dendrite defects due to loss of extracellular matrix adhesion, thus impairing
      growth within a 2D plane. We provide evidence that Ret interacts with integrins
      to regulate dendrite adhesion via rac1. In addition, Ret is required for dendrite
      stability and normal F-actin distribution suggesting it has an essential role in
      dendrite maintenance. We propose novel functions for Ret as a regulator in
      dendrite patterning and adhesion distinct from its role in axon guidance. 

PMID- 25764306
TI  - MRSA as a rare cause of vaginitis.
AB  - We describe a 26-year-old otherwise healthy woman with MRSA vaginitis.
      Traditional MRSA risk factors were absent and additional screening sites were
      negative. Patient was treated successfully with oral antibiotics combined with
      topical lactic acid emulsion. Because her partner appeared to have solitary MRSA
      carriage on the glans, a suggestion of sexual transmission was made. He was
      treated successfully with topical mupirocin ointment. Although solitary vaginal
      MRSA carriage and infection seems to be rare and its clinical impact is yet
      undefined, clinicians should consider adding the genitourinary tract to
      traditional screening sites in case of recurrent MRSA infections. 

PMID- 25764307
TI  - Effect of the small-world structure on encoding performance in the primary visual
      cortex: an electrophysiological and modeling analysis.
AB  - The biological networks have been widely reported to present small-world
      properties. However, the effects of small-world network structure on population's
      encoding performance remain poorly understood. To address this issue, we applied
      a small world-based framework to quantify and analyze the response dynamics of
      cell assemblies recorded from rat primary visual cortex, and further established
      a population encoding model based on small world-based generalized linear model
      (SW-GLM). The electrophysiological experimental results show that the small world
      based population responses to different topological shapes present significant
      variation (t test, p < 0.01; effect size: Hedge's g > 0.8), while no significant
      variation was found for control networks without considering their spatial
      connectivity (t test, p > 0.05; effect size: Hedge's g < 0.5). Furthermore, the
      numerical experimental results show that the predicted response under SW-GLM is
      more accurate and reliable compared to the control model without small-world
      structure, and the decoding performance is also improved about 10 % by taking the
      small-world structure into account. The above results suggest the important role
      of the small-world neural structure in encoding visual information for the neural
      population by providing electrophysiological and theoretical evidence,
      respectively. The study helps greatly to well understand the population encoding
      mechanisms of visual cortex.

PMID- 25764308
TI  - Species-specificity of temporal processing in the auditory midbrain of gray
      treefrogs: interval-counting neurons.
AB  - Interval-counting neurons (ICNs) respond after a threshold number of sound pulses
      have occurred with specific intervals; a single aberrant interval can reset the
      counting process. Female gray treefrogs, Hyla chrysoscelis and H. versicolor,
      discriminate against synthetic 'calls' possessing a single interpulse interval 2
      3 three times the optimal value, suggesting that ICNs are important for call
      recognition. The calls of H. versicolor consist of pulses that are longer in
      duration, rise more slowly in amplitude and are repeated at a slower rate than
      those of H. chrysoscelis. Results of recordings from midbrain auditory neurons in
      these species include: (1) ICNs were found in both species and their temporal
      selectivity appeared to result from interplay between excitation and inhibition;
      (2) band-pass cells in H. versicolor were tuned to slower pulse rates than those
      in H. chrysoscelis; (3) ICNs that were selective for slow-rise pulse shape were
      found almost exclusively in H. versicolor, but fast-rise-selective neurons were
      found in both species, and (4) band-suppression ICNs in H. versicolor showed
      response minima at higher pulse rates than those in H. chrysoscelis. Selectivity
      of midbrain ICNs for pulse rise time and repetition rate thus correlate well with
      discriminatory abilities of these species that promote reproductive isolation. 

PMID- 25764309
TI  - Glycerol production by fermenting yeast cells is essential for optimal bread
      dough fermentation.
AB  - Glycerol is the main compatible solute in yeast Saccharomyces cerevisiae. When
      faced with osmotic stress, for example during semi-solid state bread dough
      fermentation, yeast cells produce and accumulate glycerol in order to prevent
      dehydration by balancing the intracellular osmolarity with that of the
      environment. However, increased glycerol production also results in decreased CO2
      production, which may reduce dough leavening. We investigated the effect of yeast
      glycerol production level on bread dough fermentation capacity of a commercial
      bakery strain and a laboratory strain. We find that Deltagpd1 mutants that show
      decreased glycerol production show impaired dough fermentation. In contrast,
      overexpression of GPD1 in the laboratory strain results in increased fermentation
      rates in high-sugar dough and improved gas retention in the fermenting bread
      dough. Together, our results reveal the crucial role of glycerol production level
      by fermenting yeast cells in dough fermentation efficiency as well as gas
      retention in dough, thereby opening up new routes for the selection of improved
      commercial bakery yeasts. 

PMID- 25764310
TI  - Clinical outcome of HIV viraemic controllers and noncontrollers with normal CD4
      counts is exclusively determined by antigen-specific CD8+ T-cell-mediated HIV
      suppression.
AB  - In this cross-sectional study we evaluated T-cell responses using several assays
      to determine immune correlates of HIV control that distinguish untreated viraemic
      controllers (VC) from noncontrollers (NC) with similar CD4 counts. Samples were
      taken from 65 ART-naive chronically HIV-infected VC and NC from Thailand with
      matching CD4 counts in the normal range (>450 cells/MUl). We determined HIVp24
      specific T-cell responses using standard Interferon-gamma (IFNgamma) ELISpot
      assays, and compared the functional quality of HIVp24-specific CD8+ T-cell
      responses using polychromatic flow cytometry. Finally, in vitro HIV suppression
      assays were performed to evaluate directly the activity of CD8+ T cells in HIV
      control. Autologous CD4+ T cells were infected with primary patient-derived HIV
      isolates and the HIV suppressive activity of CD8+ T cells was determined after co
      culture, measuring production of HIVp24 Ag by ELISA. The HIVp24-specific T-cell
      responses of VC and NC could not completely be differentiated through measurement
      of IFNgamma-producing cells using ELISpot assays, nor by the absolute cell
      numbers of polyfunctional HIVp24-specific CD8+ T cells. However, in vitro HIV
      suppression assays showed clear differences between VC and NC. HIV suppressive
      activity, mediated by either ex vivo unstimulated CD8+ T cells or HIVp24-specific
      T-cell lines, was significantly greater using cells from VC than NC cells.
      Additionally, we were able to demonstrate a significant correlation between the
      level of HIV suppressive activity mediated by ex vivo unstimulated CD8+ T cells
      and plasma viral load (pVL) (Spearman r = -0.7345, p = 0.0003). This study
      provides evidence that in vitro HIV suppression assays are the most informative
      in the functional evaluation of CD8+ T-cell responses and can distinguish between
      VC and NC. 

PMID- 25764312
TI  - Experimentally observe the effect of spherical aberration on diffractive
      intraocular lens using adaptive optics.
AB  - We first investigated the similarity in optical quality of a batch of diffractive
      intraocular lenses (DIOLs), providing experimental evidence for one DIOL as
      representative of a batch. Using adaptive optics, we then evaluated one DIOL
      under different levels of Zernike spherical aberration (SA) by applying both a
      point spread function test and a psychophysical visual acuity test. We found that
      for small aperture size SA has the effect of shifting the through-focus curve of
      DIOL. Also, for a relatively large aperture size, it has different effects on the
      distant and near foci.

PMID- 25764311
TI  - Comparison of the management and in-hospital outcomes of acute coronary syndrome
      patients in Australia and New Zealand: results from the binational SNAPSHOT acute
      coronary syndrome 2012 audit.
AB  - BACKGROUND/AIMS: We aimed to assess differences in patient management, and
      outcomes, of Australian and New Zealand patients admitted with a suspected or
      confirmed acute coronary syndrome (ACS). METHODS: We used comprehensive data from
      the binational Australia and New Zealand ACS 'SNAPSHOT' audit, acquired on
      individual patients admitted between 00.00 h on 14 May 2012 to 24.00 h on 27 May
      2012. RESULTS: There were 4387 patient admissions, 3381 (77%) in Australia and
      1006 (23%) in New Zealand; Australian patients were slightly younger (67 vs 69
      years, P = 0.0044). Of the 2356 patients with confirmed ACS, Australian patients
      were at a lower cardiovascular risk with a lower median Global Registry Acute
      Coronary Events score (147 vs 154 P = 0.0008), but as likely to receive an
      invasive coronary angiogram (58% vs 54%, P = 0.082), or revascularisation with
      percutaneous coronary intervention (32% vs 31%, P = 0.92) or coronary artery
      bypass graft surgery (7.0% vs 5.6%, P = 0.32). Of the 1937 non-segment elevation
      myocardial infarction/unstable angina pectoris (NSTEMI/UAP) patients, Australian
      patients had a shorter time to angiography (46 h vs 67 h, P < 0.0001). However,
      at discharge, Australian NSTEMI/UAP survivors were less likely to receive aspirin
      (84% vs 89%, P = 0.0079, a second anti-platelet agent (57% vs 63%, P = 0.050) or
      a beta blocker (67% vs 77%, P = 0.0002). In-hospital death rates were not
      different (2.7% vs 3.2%, P = 0.55) between Australia and New Zealand.
      CONCLUSIONS: Overall more similarities were seen, than differences, in the
      management of suspected or confirmed ACS patients between Australia and New
      Zealand. However, in several management areas, both countries could improve the
      service delivery to this high-risk patient group.

PMID- 25764313
TI  - Evaluation of the usefulness of three-dimensional optical coherence tomography in
      a guinea pig model of endolymphatic hydrops induced by surgical obliteration of
      the endolymphatic duct.
AB  - Optical coherence tomography (OCT) has advanced significantly over the past two
      decades and is currently used extensively to monitor the internal structures of
      organs, particularly in ophthalmology and dermatology. We used ethylenediamine
      tetra-acetic acid (EDTA) to decalcify the bony walls of the cochlea and
      investigated the inner structures by deep penetration of light into the cochlear
      tissue using OCT on a guinea pig model of endolymphatic hydrops (EH), induced by
      surgical obliteration of the endolymphatic duct. The structural and functional
      changes associated with EH were identified using OCT and auditory brainstem
      response tests, respectively. We also evaluated structural alterations in the
      cochlea using three-dimensional reconstruction of the OCT images, which clearly
      showed physical changes in the cochlear structures. Furthermore, we found
      significant anatomical variations in the EH model and conducted graphical
      analysis by strial atrophy for comparison. The physical changes included damage
      to and flattening of the organ of Corti-evidence of Reissner's membrane
      distention-and thinning of the lateral wall. These results indicate that
      observation of EDTA-decalcified cochlea using OCT is significant in examination
      of gradual changes in the cochlear structures that are otherwise not depicted by
      hematoxylin and eosin staining.

PMID- 25764314
TI  - Endophthalmitis caused by Staphylococcus hominis and two different colonies of
      Staphylococcus haemolyticus after cataract surgery.
AB  - PURPOSE: To describe a case of endophthalmitis after cataract surgery caused by
      Staphylococcus hominis and two separate colony types of Staphylococcus
      haemolyticus. METHODS: Retrospective chart review including ophthalmic
      examination, intraocular biopsy and cultures, and anterior segment photography.
      RESULTS: A patient presented with endophthalmitis 1 month after cataract surgery.
      The patient underwent pars plana vitrectomy with vitreous fluid, aqueous fluid,
      and lens capsule biopsy with injection of intravitreal antimicrobials with full
      resolution of the infection. Cultures isolated grew S. hominis and two different
      colonies of S. haemolyticus, all sensitive to vancomycin. CONCLUSION: To the best
      of the authors' knowledge, this is the first case of endophthalmitis due to lens
      capsule seeding from three different types of bacteria, S. hominis and two
      different colony types of S. haemolyticus. Prompt diagnosis and treatment can be
      associated with good visual outcomes.

PMID- 25764315
TI  - Remission of nonparaneoplastic autoimmune retinopathy after minimal steroid
      treatment.
AB  - PURPOSE: To describe the clinical findings in a patient demonstrating recovery
      from nonparaneoplastic autoimmune retinopathy after a minimal course of steroid
      treatment. METHODS: Clinical presentation was documented, and paraclinical tests
      were obtained using Humphrey automated perimetry for visual fields, Western
      blotting for antiretinal antibodies, and electroretinography for evaluation of
      rod and cone function. RESULTS: Initial presentation revealed marked visual field
      deficits, electroretinographic dysfunction, and the presence of alpha-enolase
      autoantibodies. After a brief course of oral corticosteroids, the patient
      demonstrated improvement in visual fields, disappearance of alpha-enolase
      autoantibodies, partial recovery of the cone on-response, and complete recovery
      of the rod response. CONCLUSION: This case is distinguished from previous reports
      by the rapidity and degree of recovery, the brevity of treatment required, and
      the unique electroretinographic recovery pattern with concomitant disappearance
      of alpha-enolase autoantibodies. These findings suggest a pathologic role for
      alpha-enolase autoantibodies in autoimmune rod bipolar cell dysfunction.
      Identification of other cases exhibiting such improvements and associated
      autoantibody activity may expand our understanding of nonparaneoplastic
      autoimmune retinopathy disease pathogenesis.

PMID- 25764316
TI  - Occlusive vasculitis due to hyperacute Streptococcus mitis endophthalmitis after
      intravitreal ranibizumab.
AB  - PURPOSE: To report a case of hyperacute Streptococcus mitis endophthalmitis after
      intravitreal ranibizumab resulting in occlusive vasculitis. METHODS:
      Retrospective case report with ultra-wide-field color fundoscopic and fluorescein
      angiographic imaging. RESULTS: An 83-year-old woman received an intravitreal
      injection of ranibizumab to her right eye and was evaluated the next day (less
      than 24 hours from the injection) because of acute loss of vision. Her vision had
      decreased from 20/50 to hand motions in the right eye at the time of
      reevaluation. Wide-field fundus photography demonstrated pallid optic nerve head
      edema, generalized vascular attenuation, diffuse vascular sheathing, and
      scattered large postequatorial intraretinal hemorrhages. Ultra-wide-field
      fluorescein angiography revealed a severely delayed AV transit time associated
      with extensive areas of retinal nonperfusion and late retinal vascular leakage
      consistent with occlusive vasculitis. She underwent immediate pars plana
      vitrectomy with extensive irrigation of the vitreous cavity and intravitreal
      injection of antibiotics. In light of a worsening clinical course, she was taken
      for repeat vitrectomy 1 week later with panretinal endolaser photocoagulation,
      instillation of silicone oil, and sub-Tenon triamcinolone acetonide. At
      postoperative month 1, she maintained 20/200 vision with improved retinal
      perfusion on fluorescein angiography. CONCLUSION: We describe a hyperacute case
      of S. mitis endophthalmitis after intravitreal injection with ranibizumab,
      associated with severe occlusive vasculitis on ultra-wide-field fluorescein
      angiography. Aggressive early surgical intervention may be associated with better
      outcomes than previously reported.

PMID- 25764317
TI  - Cystoid macular edema and macular pigmentation associated with nab-Paclitaxel
      therapy.
AB  - PURPOSE: To report the first known case of retinal pigment epithelium
      hyperpigmentation changes and cystoid macular edema in a patient on nab
      paclitaxel therapy. METHODS: Observational case report. RESULTS: A 72-year-old
      man on nab-paclitaxel therapy for non-small cell lung carcinoma developed cystoid
      macular edema with minimal capillary leakage with subsequent retinal pigment
      epithelium hyperpigmentation after resolution of cystoid macular edema.
      CONCLUSION: Nab-paclitaxel therapy may be associated with the development of
      retinal pigment epithelium hyperpigmentation in the setting of resolved minimal
      capillary leakage cystoid macular edema.

PMID- 25764318
TI  - N-Aryl-5-aminopyrazole: a versatile architecture in medicinal chemistry.
AB  - N-Aryl-5-aminopyrazole represents a key structural motif in a plethora of
      biologically active molecules endowed with a wide spectrum of pharmacological
      properties. Accordingly, this scaffold can be certainly included in the category
      of a privileged structure. As an example, N-aryl-5- aminopyrazole along with its
      5-ureido derivatives are recurrent scaffolds in the field of inhibition of the
      different members of mitogen-activated protein kinases (MAPKs). Over the past
      recent years a large number of papers highlighting the design, synthesis and
      biological evaluation of different classes of N-aryl-5-aminopyrazole-containing
      compounds have been reported in the literature, but a review on this topic is
      still missing. With the aim to fill this gap, the present review article focuses
      on the recent developments (1995-mid2014) on the application of the N-aryl-5
      aminopyrazole-based compounds in different therapeutic fields, with a particular
      attention to the design and structure-activity relationships (SAR) aspects of
      each class of compounds. 

PMID- 25764319
TI  - Oil body-mediated defense against fungi: From tissues to ecology.
AB  - Oil bodies are localized in the seed cells and leaf cells of many land plants.
      They have a passive function as storage organelles for lipids. We recently
      reported that the leaf oil body has an active function as a subcellular factory
      that produces an antifungal oxylipin during fungal infection in Arabidopsis
      thaliana. Here, we propose a model for oil body-mediated plant defense.
      Remarkably, senescent leaves develop oil bodies and accumulate alpha-dioxygenase1
      (alpha-DOX1) and caleosin3 (CLO3) on the oil-body membrane, which catalyze the
      conversion of alpha-linolenic acid to the phytoalexin 2-hydroxy-octadecatrienoic
      acid (2-HOT). The model proposes that senescent leaves actively produce
      antifungal oxylipins and phytoalexins, and abscised leaves contain a mixture of
      antifungal compounds. In natural settings, the abscised leaves with antifungal
      compounds accumulate in leaf litter and function to protect healthy tissues and
      young plants from fungal infection. Plants might have evolved this ecological
      function for dead leaves. 

PMID- 25764320
TI  - Vemurafenib mucosal side-effect.

PMID- 25764321
TI  - Rate control management of atrial fibrillation: may a mathematical model suggest
      an ideal heart rate?
AB  - BACKGROUND: Despite the routine prescription of rate control therapy for atrial
      fibrillation (AF), clinical evidence demonstrating a heart rate target is
      lacking. Aim of the present study was to run a mathematical model simulating AF
      episodes with a different heart rate (HR) to predict hemodynamic parameters for
      each situation. METHODS: The lumped model, representing the pumping heart
      together with systemic and pulmonary circuits, was run to simulate AF with HR of
      50, 70, 90, 110 and 130 bpm, respectively. RESULTS: Left ventricular pressure
      increased by 57%, from 33.92+/-37.56 mmHg to 53.15+/-47.56 mmHg, and mean
      systemic arterial pressure increased by 27%, from 82.66+/-14.04 mmHg to 105.3+/
      7.6 mmHg, at the 50 and 130 bpm simulations, respectively. Stroke volume (from
      77.45+/-8.50 to 39.09+/-8.08 mL), ejection fraction (from 61.10+/-4.40 to 39.32+/
      5.42%) and stroke work (SW, from 0.88+/-0.04 to 0.58+/-0.09 J) decreased by 50,
      36 and 34%, at the 50 and 130 bpm simulations, respectively. In addition, oxygen
      consumption indexes (rate pressure product - RPP, tension time index per minute -
      TTI/min, and pressure volume area per minute - PVA/min) increased from the 50 to
      the 130 bpm simulation, respectively, by 186% (from 5598+/-1939 to 15995+/-3219
      mmHg/min), 56% (from 2094+/-265 to 3257+/-301 mmHg s/min) and 102% (from 57.99+/
      17.90 to 117.4+/-26.0 J/min). In fact, left ventricular efficiency (SW/PVA)
      decreased from 80.91+/-2.91% at 50 bpm to 66.43+/-3.72% at the 130 bpm HR
      simulation. CONCLUSION: Awaiting compulsory direct clinical evidences, the
      present mathematical model suggests that lower HRs during permanent AF relates to
      improved hemodynamic parameters, cardiac efficiency, and lower oxygen
      consumption.

PMID- 25764322
TI  - The role of ponatinib in Philadelphia chromosome-positive acute lymphoblastic
      leukemia.
AB  - The introduction of tyrosine kinase inhibitors has improved outcomes in
      Philadelphia chromosome-positive acute lymphoblastic leukemia, yet relapse due to
      the development of resistance mutations remains a major obstacle. Ponatinib is a
      novel tyrosine kinase inhibitor designed to overcome single-resistance mutations
      in the ABL kinase. Three clinical trials confirmed the efficacy of ponatinib in
      the relapsed and front-line setting in Philadelphia positive acute lymphoblastic
      leukemia, even in the presence of the T315I mutation, which confers resistance to
      other tyrosine kinase inhibitors. The rate of relapse appears to be very low when
      used in combination with chemotherapy, suggesting a role for ponatinib in newly
      diagnosed patients. A major concern with the use of ponatinib is the associated
      high risk of life-threatening vascular thrombotic events. Potential strategies to
      reduce this risk include minimizing the use of ponatinib in patients with
      significant baseline cardiovascular risk, careful surveillance and treatment of
      cardiovascular risk-factors and dose reduction of ponatinib.

PMID- 25764323
TI  - Analytical protocols for separation and electron microscopy of nanoparticles
      interacting with bacterial cells.
AB  - An important step toward understanding interactions between nanoparticles (NPs)
      and bacteria is the ability to directly observe NPs interacting with bacterial
      cells. NP-bacteria mixtures typical in nanomedicine, however, are not yet
      amendable for direct imaging in solution. Instead, evidence of NP-cell
      interactions must be preserved in derivative (usually dried) samples to be
      subsequently revealed in high-resolution images, for example, via scanning
      electron microscopy (SEM). Here, this concept is realized for a mixed suspension
      of model NPs and Staphylococcus aureus bacteria. First, protocols for analyzing
      the relative colloidal stabilities of NPs and bacteria are developed and
      validated based on systematic centrifugation and comparison of colony forming
      unit (CFU) counting and optical density (OD) measurements. Rate-dependence of
      centrifugation efficiency for each component suggests differential sedimentation
      at a specific predicted rate as an effective method for removing free NPs after
      co-incubation; the remaining fraction comprises bacteria with any associated NPs
      and can be examined, for example, by SEM, for evidence of NP-bacteria
      interactions. These analytical protocols, validated by systematic control
      experiments and high-resolution SEM imaging, should be generally applicable for
      investigating NP-bacteria interactions. 

PMID- 25764324
TI  - Pressure-imposed changes of benzoic acid crystals.
AB  - Structural and energetic properties of benzoic acid crystals at pressure elevated
      from ambient condition up to 2.21 GPa were characterized. The directly observed
      variations of cell parameters and consequently cell volume are associated with
      many other changes including energetic, geometric, and electronic
      characteristics. First of all the non-monotonous change of lattice energy are
      noticed with the rise of pressure since the increase of stabilization up to 1GPa
      is followed by systematic decrease of lattice energies after extending the
      hydrostatic compression. There is also an observed increase of C2(2)(8) synthon
      stabilization interaction with increase of pressure. The lattice response rather
      than interaction within synthons are source of observed pressure-related trend of
      lattice energy changes. The energy decomposition analysis revealed that the total
      steric interactions determine the overall trend of lattice energy change with the
      rise of pressure. Besides geometric aromaticity index was used as a measure of
      geometric changes. Serious discrepancies were noticed between HOMA values
      computed with the use of experimental and optimized geometries of the ring. Even
      inclusion of uncertainties of experimental geometries related to limited
      precision of X-ray diffraction measurements does not cancel mentioned
      discrepancies. Although HOMA exhibit similar trends at modest pressures the
      diversity became surprisingly high at more extreme conditions. This might suggest
      limitations of periodic DFT computations at elevated pressures and the
      experimentally observed breaking of molecules at very high pressures will
      probably not be accounted properly in this approach. Also limitation of direct
      use of experimental geometries were highlighted.

PMID- 25764325
TI  - Influence of GHz electric fields on the mechanical properties of a microtubule.
AB  - The effects of external GHz electric fields on the mechanical properties of a
      microtubule (MT) have been modeled through the application of a molecular
      dynamics simulation method. To explore the properties of the MT, two different
      systems each consisting of a pair of dimers were exposed to an 0.03 V/nm electric
      field with a frequency ranging between 1 to 10 GHz. It was found that the Young's
      modulus of each system, which is related to the flexibility of the MT, was lower
      at some frequencies and higher at others in comparison with normal biological
      conditions. Hence, the application of such an electric field with a frequency in
      this range may affect MT function, which could have positive or negative effects
      on cell health. Positive effects include its potential use in cancer treatment,
      where the application of such a field could lead to a decrease in MT rigidity,
      similar to the effect of Taxol on MTs. Negative effects include unwanted changes
      to the mechanical properties of MTs (e.g., disturbing the cell division process
      and in turn increasing the risk of cancer) upon the application of such a field. 

PMID- 25764327
TI  - Gerard van Swieten 1700-1772.

PMID- 25764326
TI  - Conformational landscape and low lying excited states of imatinib.
AB  - The conformational changes of imatinib (IMT) are crucial for understanding the
      ligand-receptor interaction and its mechanism of action [Agofonov et al. (2014)
      Nature Struct Mol Biol 21:848-853]. Therefore, here we investigated the free
      energy conformational landscape of the free IMT base, aiming to describe the
      three-dimensional structures and energetic stability of its conformers. Forty
      five unique conformers, within an energy window of 4.8 kcal mol(-1) were
      identified by a conformational search in gas-phase, at the B3LYP/6-31G(d)
      theoretical level. Among these, the 20 most stable, as well as 4 conformers
      resulting from optimization of experimental structures found in the two known
      polymorphs of IMT and in the c-Abl complex were further refined using the 6
      31+G(d,p) basis set and the polarizable continuum solvation model. The most
      stable conformers in gas-phase and water exhibit a V-shaped structure. The major
      difference between the most stable free conformers and the bioactive conformers
      consists in the relative orientation of the pyrimidine-pyridine groups
      responsible for hydrogen bonding interactions in the ATP-binding pocket. The
      ratio of mole fractions corresponding to the two known (alpha and beta)
      polymorphic forms of IMT was estimated from the calculated thermochemical data,
      in quantitative agreement with the existing experimental data related to their
      solubility. The electronic absorption spectrum of this compound was investigated
      in water and explained based on the theoretical TD-DFT results, considering the
      Boltzmann population-averaged computed data at CAM-B3LYP/6-31+G(d,p) level of
      theory for the nine most stable conformers. 

PMID- 25764328
TI  - Effect of changing NAVA levels on peak inspiratory pressures and electrical
      activity of the diaphragm in premature neonates.
AB  - BACKGROUND: Neurally adjusted ventilator assist (NAVA) uses electrical activity
      of the diaphragm (Edi) to provide patient-directed ventilatory support. The NAVA
      level determines the proportional amount of ventilatory support. Systematically
      increasing NAVA level initially increases peak inspiratory pressure (PIP) while
      maintaining a constant Edi until a breakpoint (BrP) is reached. Further increases
      in NAVA level reduce the Edi, while the PIP plateaus. This study was performed to
      establish whether premature neonates have intact neural feedback systems allowing
      them to have a BrP. METHOD: NAVA level was increased by 0.5 cm H2O MUV(-1) every
      3 min from 0.5 to 4.0 cm H2O MUV(-1). PIP, Edi, mean blood pressure, heart rate,
      respiratory rate, oxygen saturation and FIO2 were recorded. Statistics: Non
      linear regression was done for PIP and Edi. Linear regression was done for the
      other variables. The data from the trials were combined by normalizing to NAVA
      levels above and below the BrP. RESULT: Nine neonates were studied on NAVA and 12
      on non-invasive NAVA. PIP increased until the BrP was reached and then remained
      unchanged. Edi decreased after the BrP was reached. All other variables remained
      unchanged. CONCLUSION: Neonates demonstrated a BrP suggesting intact neural
      feedback mechanisms that may protect lungs from over distention with NAVA
      ventilation.

PMID- 25764329
TI  - One-time umbilical cord milking after cord cutting has same effectiveness as
      multiple-time umbilical cord milking in infants born at <29 weeks of gestation: a
      retrospective study.
AB  - OBJECTIVE: To compare two strategies to potentiate the effects of placental
      transfusion in infants born at <29 weeks of gestation. STUDY DESIGN: Twenty
      infants who received one-time umbilical cord milking after umbilical cord cutting
      were compared with 20 infants from a previous study group who received multiple
      time umbilical cord milking. The primary outcome measurements were the
      probability of not needing a red blood cell (RBC) transfusion during the hospital
      stay and the total number of RBC transfusions within 21 days after birth. RESULT:
      There was no significant difference in the probability of not needing a
      transfusion during the hospital stay (P=0.75) and the mean number of RBC
      transfusions given within the first 21 days of life (1.1+/-1.8 for the one-time
      umbilical cord-milking group vs 0.7+/-1.2 for the multiple-time umbilical cord
      milking group, P=0.48). CONCLUSION: One-time umbilical cord milking after
      umbilical cord cutting had similar beneficial effects to multiple-time umbilical
      cord milking before umbilical cord cutting in very premature infants.

PMID- 25764330
TI  - Interplay between DNA supercoiling and transcription elongation.
AB  - Transcription-coupled DNA supercoiling has been shown to be an important
      regulator of transcription that is broadly present in the cell. Here we review
      experimental work which shows that RNA polymerase is a powerful torsional motor
      that can alter DNA topology and structure, and DNA supercoiling in turn directly
      affects transcription elongation. 

PMID- 25764331
TI  - lncRNA and gene looping: what's the connection?
AB  - Recent functional studies have unveiled the significant role chromatin topology
      plays in gene regulation. Several lines of evidence suggest genes access
      necessary factors for transcription by forming chromatin loops. A clearer picture
      of the players involved in chromatin organization, including lncRNA, is emerging.

PMID- 25764332
TI  - The Old and New Testaments of gene regulation. Evolution of multi-subunit RNA
      polymerases and co-evolution of eukaryote complexity with the RNAP II CTD.
AB  - I relate a story of genesis told from the point of view of multi-subunit RNA
      polymerases (RNAPs) including an Old Testament (core RNAP motifs in all cellular
      life) and a New Testament (the RNAP II heptad repeat carboxy terminal domain
      (CTD) and CTD interactome in eukarya). The Old Testament: at their active site,
      one class of eukaryotic interfering RNAP and ubiquitous multi-subunit RNAPs each
      have two-double psi beta barrel (DPBB) motifs (a distinct pattern for compact 6
      beta sheet barrels). Between beta sheets 2 and 3 of the beta subunit type DPBB of
      all multi-subunit RNAPs is a sandwich barrel hybrid motif (SBHM) that interacts
      with conserved initiation and elongation factors required to utilize a DNA
      template. Analysis of RNAP core protein motifs, therefore, indicates that RNAP
      evolution can be traced from the RNA-protein world to LUCA (the last universal
      common ancestor) branching to LECA (the last eukaryotic common ancestor) and to
      the present day, spanning about 4 billion years. The New Testament: in the
      eukaryotic lineage, I posit that splitting RNAP functions into RNAPs I, II and
      III and innovations developed around the CTD heptad repeat of RNAP II and the
      extensive CTD interactome helps to describe how greater structural, cell cycle,
      epigenetic and signaling complexity co-evolved in eukaryotes relative to
      eubacteria and archaea. 

PMID- 25764333
TI  - Long range chromatin organization: a new layer in splicing regulation?
AB  - Splicing is a predominantly co-transcriptional process that has been shown to be
      tightly coupled to transcription. Chromatin structure is a key factor that
      mediates this functional coupling. In light of recent evidence that shows the
      importance of higher order chromatin organization in the coordination and
      regulation of gene expression, we discuss here the possible roles of long-range
      chromatin organization in splicing and alternative splicing regulation. 

PMID- 25764334
TI  - Variation in vertebrate cis-regulatory elements in evolution and disease.
AB  - Much of the genetic information that drives animal diversity lies within the vast
      non-coding regions of the genome. Multi-species sequence conservation in non
      coding regions of the genome flags important regulatory elements and more
      recently, techniques that look for functional signatures predicted for regulatory
      sequences have added to the identification of thousands more. For some time,
      biologists have argued that changes in cis-regulatory sequences creates the basic
      genetic framework for evolutionary change. Recent advances support this notion
      and show that there is extensive genomic variability in non-coding regulatory
      elements associated with trait variation, speciation and disease. 

PMID- 25764335
TI  - Activation and reactivation of the RNA polymerase II trigger loop for intrinsic
      RNA cleavage and catalysis.
AB  - In addition to RNA synthesis, multisubunit RNA polymerases (msRNAPs) support
      enzymatic reactions such as intrinsic transcript cleavage. msRNAP active sites
      from different species appear to exhibit differential intrinsic transcript
      cleavage efficiency and have likely evolved to allow fine-tuning of the
      transcription process. Here we show that a single amino-acid substitution in the
      trigger loop (TL) of Saccharomyces RNAP II, Rpb1 H1085Y, engenders a gain of
      intrinsic cleavage activity where the substituted tyrosine appears to participate
      in acid-base chemistry at alkaline pH for both intrinsic cleavage and nucleotidyl
      transfer. We extensively characterize this TL substitution for each of these
      reactions by examining the responses RNAP II enzymes to catalytic metals, altered
      pH, and factor inputs. We demonstrate that TFIIF stimulation of the first
      phosphodiester bond formation by RNAP II requires wild type TL function and that
      H1085Y substitution within the TL compromises or alters RNAP II responsiveness to
      both TFIIB and TFIIF. Finally, Mn(2+) stimulation of H1085Y RNAP II reveals
      possible allosteric effects of TFIIB on the active center and cooperation between
      TFIIB and TFIIF. 

PMID- 25764336
TI  - Setting limits: maintaining order in a large gene family.
AB  - Odorant receptor (OR) gene choice is a paradigmatic example of stochastic
      regulation in which olfactory neurons choose one OR from > 1,000 possibilities.
      Recent biochemical, mathematical, and in vivo findings have revealed key players,
      introduced new axes of control, and brought the core mechanisms of the process
      into sharper focus. 

PMID- 25764339
TI  - Temporal SILAC-based quantitative proteomics identifies host factors involved in
      chikungunya virus replication.
AB  - Chikungunya virus (CHIKV) is an arthropod-borne reemerging human pathogen that
      generally causes a severe persisting arthritis. Since 2005, the virus has
      infected millions of people during outbreaks in Africa, Indian Ocean Islands,
      Asia, and South/Central America. Many steps of the replication and expression of
      CHIKV's 12-kb RNA genome are highly dependent on cellular factors, which thus
      constitute potential therapeutic targets. SILAC and LC-MS/MS were used to define
      the temporal dynamics of the cellular response to infection. Using samples
      harvested at 8, 10, and 12 h postinfection, over 4700 proteins were identified
      and per time point 2800-3500 proteins could be quantified in both biological
      replicates. At 8, 10, and 12 h postinfection, 13, 38, and 106 proteins,
      respectively, were differentially expressed. The majority of these proteins
      showed decreased abundance. Most subunits of the RNA polymerase II complex were
      progressively degraded, which likely contributes to the transcriptional host shut
      off observed during CHIKV infection. Overexpression of four proteins that were
      significantly downregulated (Rho family GTPase 3 (Rnd3), DEAD box helicase 56
      (DDX56), polo-like kinase 1 (Plk1), and ubiquitin-conjugating enzyme E2C (UbcH10)
      reduced susceptibility of cells to CHIKV infection, suggesting that infection
      induced downregulation of these proteins is beneficial for CHIKV replication. All
      MS data have been deposited in the ProteomeXchange with identifier PXD001330
      (http://proteomecentral.proteomexchange.org/dataset/PXD001330). 

PMID- 25764338
TI  - Biochemical and Molecular Alterations Following Arsenic-Induced Oxidative Stress
      and Mitochondrial Dysfunction in Rat Brain.
AB  - Oxidative stress is associated with the generation of reactive oxygen species
      (ROS), which is supposed to be one of the mechanisms of arsenic-induced
      neurodegeneration. Mitochondria, being the major source of ROS generation may
      present an important target of arsenic-mediated neurotoxicity. Hence, we planned
      the study to elucidate the possible biochemical and molecular alterations induced
      by arsenic exposure in rat brain mitochondria. Chronic sodium arsenite treatment
      (25 ppm for 12 weeks) resulted in decreased activity of mitochondrial complexes
      I, II, and IV followed by increased ROS generation. There was decrease in
      mitochondrial superoxide dismutase (MnSOD) activity in arsenic-treated rat brain
      further showing increased superoxide radical generation in mitochondria. The
      decrease in MnSOD activity might be responsible for the increased protein and
      lipid oxidation as observed in our study. Protein and messenger RNA (mRNA) levels
      of MnSOD and mitochondrial uncoupling protein 2 (UCP-2) were downregulated
      suggesting decreased removal of ROS in rat brain. Fourier transform infrared
      (FTIR) spectroscopy analysis revealed significant decrease in amide A, amide I,
      amide II, and Olefinic = CH stretching band area suggesting molecular alteration
      in proteins and lipids after arsenic treatment. The results of present study
      indicate that arsenic-induced disturbed mitochondrial metabolism, decreased
      removal of ROS, decrease in protein synthesis, and altered membrane lipid
      polarity and fluidity may be responsible for the mitochondrial oxidative damage
      in rat brain that may further be implicated as contributing factor in arsenic
      induced neurodegeneration. 

PMID- 25764340
TI  - International students in speech-language pathology clinical education
      placements: Perceptions of experience and competency development.
AB  - PURPOSE: This study aimed to describe perceptions of clinical placement
      experiences and competency development for international speech-language
      pathology students and to determine if these perceptions were different for
      domestic students. METHOD: Domestic and international students at two Australian
      universities participated in nine focus group interviews. Thematic analysis led
      to the identification of two themes shared by international and domestic students
      and several separate themes. RESULT: Shared themes identified the important
      influence of students' relationships with clinical educators, unique
      opportunities and learning that occurs on placement. International student themes
      included concerns about their communication skills and the impact of these skills
      on client progress. They also explored their adjustment to unfamiliar placement
      settings and relationships, preferring structured placements to assist this
      adjustment. Domestic student themes explored the critical nature of competency
      attainment and assessment on placement, valuing placements that enabled them to
      achieve their goals. CONCLUSION: The findings of this study suggest that
      international students experience additional communication, cultural and
      contextual demands on clinical placement, which may increase their learning
      requirements. Clinical education practices must be responsive to the learning
      needs of diverse student populations. Strategies are suggested to assist all
      students to adjust to the professional and learning expectations of clinical
      education placements.

PMID- 25764341
TI  - Broad-spectrum antimicrobial polycarbonate hydrogels with fast degradability.
AB  - In this study, a new family of broad-spectrum antimicrobial polycarbonate
      hydrogels has been successfully synthesized and characterized. Tertiary amine
      containing eight-membered monofunctional and difunctional cyclic carbonates were
      synthesized, and chemically cross-linked polycarbonate hydrogels were obtained by
      copolymerizing these monomers with a poly(ethylene glycol)-based bifunctional
      initiator via organocatalyzed ring-opening polymerization using 1,8
      diazabicyclo[5.4.0]undec-7-ene catalyst. The gels were quaternized using methyl
      iodide to confer antimicrobial properties. Stable hydrogels were obtained only
      when the bifunctional monomer concentration was equal to or higher than 12 mol %.
      In vitro antimicrobial studies revealed that all quaternized hydrogels exhibited
      broad-spectrum antimicrobial activity against Staphylococcus aureus (Gram
      positive), Escherichia coli (Gram-negative), Pseudomonas aeruginosa (Gram
      negative), and Candida albicans (fungus), while the antimicrobial activity of the
      nonquaternized hydrogels was negligible. Moreover, the gels showed fast
      degradation at room temperature (4-6 days), which makes them ideal candidates for
      wound healing and implantable biomaterials. 

PMID- 25764342
TI  - Managing expectations when publishing tools and methods for computational
      proteomics.
AB  - Computational tools are pivotal in proteomics because they are crucial for
      identification, quantification, and statistical assessment of data. The gateway
      to finding the best choice of a tool or approach for a particular problem is
      frequently journal articles, yet there is often an overwhelming variety of
      options that makes it hard to decide on the best solution. This is particularly
      difficult for nonexperts in bioinformatics. The maturity, reliability, and
      performance of tools can vary widely because publications may appear at different
      stages of development. A novel idea might merit early publication despite only
      offering proof-of-principle, while it may take years before a tool can be
      considered mature, and by that time it might be difficult for a new publication
      to be accepted because of a perceived lack of novelty. After discussions with
      members of the computational mass spectrometry community, we describe here
      proposed recommendations for organization of informatics manuscripts as a way to
      set the expectations of readers (and reviewers) through three different
      manuscript types that are based on existing journal designations. Brief
      Communications are short reports describing novel computational approaches where
      the implementation is not necessarily production-ready. Research Articles present
      both a novel idea and mature implementation that has been suitably benchmarked.
      Application Notes focus on a mature and tested tool or concept and need not be
      novel but should offer advancement from improved quality, ease of use, and/or
      implementation. Organizing computational proteomics contributions into these
      three manuscript types will facilitate the review process and will also enable
      readers to identify the maturity and applicability of the tool for their own
      workflows. 

PMID- 25764343
TI  - Successful behavioural strategies to increase physical activity and improve
      glucose control in adults with Type 2 diabetes.
AB  - AIMS: To explore which behaviour change techniques and other intervention
      features are associated with increased levels of physical activity and improved
      HbA1c in adults with Type 2 diabetes. METHODS: Moderator analyses were performed
      on a dataset of 21 behaviour change techniques and six intervention features
      identified in a systematic review of behavioural interventions (N = 1975 patients
      with Type 2 diabetes) to establish their associations with changes in physical
      activity and HbA1c . RESULTS: Four behaviour change techniques (prompt focus on
      past success, barrier identification/problem-solving, use of follow-up prompts
      and provide information on where and when to perform physical activity) had
      statistically significant associations with increased levels of physical
      activity. Prompt review of behavioural goals and provide information on where and
      when to perform physical activity behaviour had statistically significant
      associations with improved HbA1c . Pedometer use was associated with decreased
      levels of physical activity. CONCLUSIONS: These data suggest that clinical care
      teams can optimise their consultations by incorporating specific behaviour change
      techniques that are associated with increased levels of physical activity and
      improved long-term glycaemic control.

PMID- 25764344
TI  - Reporting on the heart.

PMID- 25764346
TI  - Rumen function in vivo and in vitro in sheep fed Leucaena leucocephala.
AB  - The effect of Leucaena leucocephala inclusion in sheep diets upon rumen function
      was evaluated. Nine Pelibuey sheep, 32.6 +/- 5.33 kg live weight (LW), fitted
      with rumen cannula were used. A complete randomized block design was employed.
      Two experimental periods of 60 days each, with 60-day intervals between them,
      were used. Experimental treatments were as follows (n = 6): T1 (control), 100 %
      Pennisetum purpureum grass; T2, 20 % L. leucocephala + 80 % P. purpureum; T3, 40
      % L. leucocephala + 60 % P. purpureum. In situ rumen neutral detergent fiber
      (aNDF) and crude protein (CP) degradation, dry matter intake (DMI), volatile
      fatty acids (VFA) production, estimated methane (CH4) yield, rumen pH, ammonia
      nitrogen (N-NH3), and protozoa counts were measured. The aNDF in situ rumen
      degradation of P. purpureum and leucaena was higher (P < 0.05) in T2 and T3.
      Leucaena CP degradation was higher in T2 and T3 but for P. purpureum it was only
      significantly higher in T3. Leucaena aNDF and CP degradation rate (c) was 50 %
      higher (P < 0.05) in T2 and T3, but only higher in T3 for P. purpureum. Voluntary
      intake and rumen (N-NH3) was higher in T2 and T3 (P = 0.0001, P = 0.005,
      respectively). Molar VFA proportions were similar for all treatments (P > 0.05).
      Protozoa counts and in vitro gas production (48 h) were lower in T2 and T3 (P <
      0.05, P < 0.0001). Estimated methane yield (mol CH4/day) was higher in sheep fed
      leucaena (P < 0.0001). However, CH4 yield relative to animal performance (mol
      CH4/g LW gain) was lower in T2 and T3 (P < 0.0001). In summary, these results
      indicate that including L. leucocephala in sheep diets did not modify rumen
      fermentation pattern (same VFA ratios) nor reduce the amount of CH4 per unit of
      DMI (mol CH4/g DMI). However, leucaena inclusion does increase rumen N-NH3, aNDF
      and CP digestibility, and voluntary intake. 

PMID- 25764347
TI  - [Necessity for standards in pediatric anesthesia].

PMID- 25764348
TI  - Expression of Caenorhabditis elegans PCS in the AtPCS1-deficient Arabidopsis
      thaliana cad1-3 mutant separates the metal tolerance and non-host resistance
      functions of phytochelatin synthases.
AB  - Phytochelatin synthases (PCS) play key roles in plant metal tolerance. They
      synthesize small metal-binding peptides, phytochelatins, under conditions of
      metal excess. Respective mutants are strongly cadmium and arsenic hypersensitive.
      However, their ubiquitous presence and constitutive expression had long suggested
      a more general function of PCS besides metal detoxification. Indeed,
      phytochelatin synthase1 from Arabidopsis thaliana (AtPCS1) was later implicated
      in non-host resistance. The two different physiological functions may be
      attributable to the two distinct catalytic activities demonstrated for AtPCS1,
      that is the dipeptidyl transfer onto an acceptor molecule in phytochelatin
      synthesis, and the proteolytic deglycylation of glutathione conjugates. In order
      to test this hypothesis and to possibly separate the two biological roles, we
      expressed a phylogenetically distant PCS from Caenorhabditis elegans in an AtPCS1
      mutant. We confirmed the involvement of AtPCS1 in non-host resistance by showing
      that plants lacking the functional gene develop a strong cell death phenotype
      when inoculated with the potato pathogen Phytophthora infestans. Furthermore, we
      found that the C. elegans gene rescues phytochelatin synthesis and cadmium
      tolerance, but not the defect in non-host resistance. This strongly suggests that
      the second enzymatic function of AtPCS1, which remains to be defined in detail,
      is underlying the plant immunity function.

PMID- 25764349
TI  - Unveiling TRPV1 spatio-temporal organization in live cell membranes.
AB  - Transient Receptor Potential Vanilloid 1 (TRPV1) is a non-selective cation
      channel that integrates several stimuli into nociception and neurogenic
      inflammation. Here we investigated the subtle TRPV1 interplay with candidate
      membrane partners in live cells by a combination of spatio-temporal fluctuation
      techniques and fluorescence resonance energy transfer (FRET) imaging. We show
      that TRPV1 is split into three populations with fairly different molecular
      properties: one binding to caveolin-1 and confined into caveolar structures, one
      actively guided by microtubules through selective binding, and one which diffuses
      freely and is not directly implicated in regulating receptor functionality. The
      emergence of caveolin-1 as a new interactor of TRPV1 evokes caveolar endocytosis
      as the main desensitization pathway of TRPV1 receptor, while microtubule binding
      agrees with previous data suggesting the receptor stabilization in functional
      form by these cytoskeletal components. Our results shed light on the hitherto
      unknown relationships between spatial organization and TRPV1 function in live
      cell membranes. 

PMID- 25764350
TI  - Dendritic morphology changes in neurons from the ventral hippocampus, amygdala
      and nucleus accumbens in rats with neonatal lesions into the prefrontal cortex.
AB  - Neonatal prefrontal cortex (nPFC) lesions in rats could be a potential animal
      model to study the early neurodevelopmental abnormalities associated with the
      behavioral and morphological brain changes observed in schizophrenia.
      Morphological alterations in pyramidal neurons from the ventral hippocampus (VH)
      have been observed in post-mortem schizophrenic brains, mainly because of
      decreased dendritic arbor and spine density. We assessed the effects of nPFC
      lesions on the dendritic morphology of neurons from the VH, basolateral-amygdala
      (BLA) and the nucleus accumbens (NAcc) in rats. nPFC lesions were made on
      postnatal day 7 (PD7), after dendritic morphology was studied by the Golgi-Cox
      stain procedure followed by Sholl analysis at PD35 (prepubertal) and PD60 (adult)
      ages. We also evaluated the effects of PFC-lesions on locomotor activity caused
      by a novel environment. Adult animals with nPFC lesions showed a decreased spine
      density in pyramidal neurons from the VH and in medium spiny cells from the NAcc.
      An increased locomotion was observed in a novel environment for adult animals
      with a PFC-lesion. Our results indicate that PFC-lesions alter the neuronal
      dendrite morphology of the NAcc and the VH, suggesting a disconnection between
      these limbic structures. The locomotion paradigms suggest that dopaminergic
      transmission is altered in the PFC lesion model. This could help to understand
      the consequences of an earlier PFC dysfunction in schizophrenia. To evaluate
      possible dendritic changes in neonatal prefrontal cortex lesions in schizophrenia
      related regions including nucleus accumbens, ventral hippocampus and basolateral
      amygdala, we used the Golgi-Cox stain samples at PD35 and PD70. Our results
      suggest that neonatal prefrontal cortex damage alters dendritic parameters in
      limbic regions, and this has potential implications for schizophrenia.

PMID- 25764351
TI  - Bulky Early-Stage Cervical Cancer (2-4 cm Lesions): Upfront Radical Trachelectomy
      or Neoadjuvant Chemotherapy Followed by Fertility-Preserving Surgery: Which Is
      the Best Option?
AB  - Radical trachelectomy is now recognized as a valid treatment option for young
      women with early-stage cervical cancer with lesions measuring less than 2 cm.
      However, for women with bulky lesions measuring greater than 2 cm, few data are
      available in the literature to guide management. There are currently 2 options
      available: either upfront radical trachelectomy or neoadjuvant chemotherapy
      followed by fertility-preserving surgery. Overall, both options offer very good
      oncologic outcome; however, the rate of fertility preservation and obstetrical
      outcome seem superior after neoadjuvant chemotherapy. Advantages and
      disadvantages of both options are discussed and a thorough literature review is
      provided. Issues to be further studied are also outlined.

PMID- 25764352
TI  - Macular Hole Closure With Internal Limiting Membrane Abrasion Technique.
AB  - IMPORTANCE: Internal limiting membrane (ILM) abrasion is an alternative surgical
      technique for successful full-thickness macular hole (MH) repair. OBJECTIVE: To
      study the effects of ILM abrasion as an alternative method of MH repair. DESIGN,
      SETTING, AND PARTICIPANTS: Retrospective consecutive case series from January
      2006 to December 2008. Demographic data and preoperative, intraoperative, and
      postoperative examination records of all patients were reviewed for patients who
      underwent ILM abrasion with a diamond-dusted membrane scraper during vitrectomy
      for MH repair. A total of 100 eyes underwent ILM abrasion as an alternative to
      traditional ILM peeling. MAIN OUTCOMES AND MEASURES: Rate of MH closure and
      visual acuity (VA) outcomes at 3 months after surgery. RESULTS: Macular hole
      closure was achieved with a single surgical procedure in 94 of 100 eyes (94.0%;
      95% CI, 87.4%-97.8%). Among all patients, the median preoperative VA was 20/100
      (range, 20/30 to hand motions; 25th quartile, 20/60; and 75th quartile, 20/160),
      and the median postoperative VA at 3 months after surgery was 20/60 (range, 20/20
      to hand motions; 25th quartile, 20/40; and 75th quartile, 20/100). Among all
      patients with stage 2 MHs, 30 of 38 patients (78.9%) had at least 2 lines of VA
      gain: 15 of 23 (65.2%) were phakic, and 15 of 15 (100%) were pseudophakic. Four
      of 38 patients (10.5%) with stage 2 MHs had at least 2 lines of VA loss, and all
      were phakic. Among all patients with stage 3 or 4 MHs, 42 of 62 (67.7%) had at
      least 2 lines of VA gain, of which 30 of 38 (78.9%) were phakic and 22 of 24
      (91.7%) were pseudophakic. Six of 62 patients (9.7%) with stage 3 or 4 MHs had at
      least 2 lines of VA loss: 4 were phakic, and 2 were pseudophakic. In total, 35.0%
      (95% CI, 25.7%-44.3%) of patients achieved 20/40 vision or better, and 52.0% (95%
      CI, 42.2%-61.8%) of patients achieved 20/50 vision or better. CONCLUSIONS AND
      RELEVANCE: Abrasion of the ILM with a diamond-dusted membrane scraper at the time
      of vitrectomy achieves high rates of MH closure. This technique avoids complete
      removal of the retinal ILM basement membrane and subjacent tissues and appears to
      provide MH closure rates similar to those of traditional ILM peeling.

PMID- 25764353
TI  - Effectiveness of chlorine dispensers in emergencies: case study results from
      Haiti, Sierra Leone, Democratic Republic of Congo, and Senegal.
AB  - Dispensers are a source-based water quality intervention with promising uptake
      results in development contexts. Dispenser programs include a tank of chlorine
      with a dosing valve that is installed next to a water source, a local Promoter
      who conducts community education and refills the Dispenser, and chlorine refills.
      In collaboration with response organizations, we assessed the effectiveness of
      Dispensers in four emergency situations. In the three initial and four sustained
      response phase evaluations, 70 Dispenser sites were visited, 2057 household
      surveys were conducted, and 1676 water samples were analyzed. Across the
      evaluations, reported Dispenser use ranged from 9 to 97%, confirmed Dispenser use
      (as measured by free chlorine residual) ranged from 5 to 87%, and effective use
      (as measured by improvement in household water quality to meet international
      standards) ranged from 0 to 81%. More effective Dispenser interventions installed
      Dispensers at point-sources, maintained a high-quality chlorine solution
      manufacturing and distribution chain, maintained Dispenser hardware, integrated
      Dispensers projects within larger water programs, remunerated Promoters, had
      experienced project staff, worked with local partners to implement the project,
      conducted ongoing monitoring, and had a project sustainability plan. Our results
      indicate that Dispensers can be, but are not always, an appropriate strategy to
      reduce the risk of waterborne diseases in emergencies. 

PMID- 25764354
TI  - Fermented green tea extract alleviates obesity and related complications and
      alters gut microbiota composition in diet-induced obese mice.
AB  - Obesity is caused by an imbalance between caloric intake and energy expenditure
      and accumulation of excess lipids in adipose tissues. Recent studies have
      demonstrated that green tea and its processed products (e.g., oolong and black
      tea) are introduced to exert beneficial effects on lipid metabolism. Here, we
      propose that fermented green tea (FGT) extract, as a novel processed green tea,
      exhibits antiobesity effects. FGT reduced body weight gain and fat mass without
      modifying food intake. mRNA expression levels of lipogenic and inflammatory genes
      were downregulated in white adipose tissue of FGT-administered mice. FGT
      treatment alleviated glucose intolerance and fatty liver symptoms, common
      complications of obesity. Notably, FGT restored the changes in gut microbiota
      composition (e.g., the Firmicutes/Bacteroidetes and Bacteroides/Prevotella
      ratios), which is reported to be closely related with the development of obesity
      and insulin resistance, induced by high-fat diets. Collectively, FGT improves
      obesity and its associated symptoms and modulates composition of gut microbiota;
      thus, it could be used as a novel dietary component to control obesity and
      related symptoms. 

PMID- 25764355
TI  - Tetrahydropyranyl, a nonaromatic acid-labile Cys protecting group for Fmoc
      peptide chemistry.
AB  - Tetrahydropyranyl (Thp), which exploits the concept of being an S,O-acetal
      nonaromatic protecting group for cysteine, has been shown to be superior to Trt,
      Dpm, Acm, and StBu in solid-phase peptide synthesis using the Fmoc/tBu strategy.
      Thus, Cys racemization and C-terminal 3-(1-piperidinyl)alanine formation were
      minimized when the Cys was protected with Thp. This nonaromatic protecting group
      also improved the solubility of Cys-containing protected peptides. 

PMID- 25764356
TI  - Preparation of nasoseptal flap in trans-sphenoidal surgery using 2-MU thulium
      laser: technical note.
AB  - OBJECTIVE: The purpose of this study was to assess the feasibility of the use of
      the 2MU-thulium laser in harvesting nasal septal flaps. BACKGROUND DATA: Nasal
      septal flaps are routinely performed in almost every trans-sphenoidal surgery.
      The preservation of the arterial vasculature is a mainstay of the procedure.
      However, the margins of the flap should be sufficiently healthy to regenerate
      faster, reducing the risk of possible complications. MATERIALS AND METHODS: Eight
      patients underwent trans-sphenoidal surgery and removal of pituitary adenomas.
      Reparation of the defect was performed with the positioning of a rotational
      vascularized nasal-septal flap. The flaps were harvested with the aid of the 2MU
      thulium laser. Every patient was then monitored for 6 months through seriated
      endoscopic endonasal controls. RESULTS: There were no complications related to
      the use of the laser, either intraoperatively, or postoperatively. The operative
      timing did not significantly differ from that of traditional techniques.
      CONCLUSIONS: The use of the 2MU-thulium laser for the harvesting of nasal septal
      vascularized flaps can be considered safe and feasible. The limited number of
      treated patients could be considered as the only restriction to the study. A
      larger study might have uncovered possible instrumentation-related complications,
      which were not observed in the present study.

PMID- 25764357
TI  - Adherence to the Western Pattern Is Potentially an Unfavorable Indicator of
      Asthenozoospermia Risk: A Case-Control Study.
AB  - OBJECTIVE: The aim of this case-control study was to examine the relationship
      between dietary patterns and asthenozoospermia risk. METHODS: In total, 107
      incident asthenozoospermic men and 235 age-matched controls were interviewed
      through the infertility clinics in Tehran, Iran, from January 2012 to November
      2013. Usual dietary intakes were collected using a semiquantitative food
      frequency questionnaire and semen quality data were analyzed according to the
      fifth edition of the World Health Organization (WHO) guidelines. Dietary patterns
      were derived using factor analysis. The first tertile served as the reference
      category for regression analyses. RESULTS: In principal component analysis, 2
      dietary patterns emerged: a "prudent pattern" (leafy green vegetables, yellow
      vegetables, other vegetables, tomatoes, fish and other seafood, fruits and
      natural fruit juices, legumes, whole grains, poultry, tea and coffee, low-fat
      dairy products, and vegetable oils) and a "Western pattern" (organ meats, red and
      processed meats, sugar, soft drinks and confectionary, pasta, rice and refined
      grains, potatoes, french fries and fast foods, high-fat dairy products,
      hydrogenated fats, mayonnaise and fatty sauces, and snacks). After adjustment for
      potential confounders, participants in the highest tertile of the prudent pattern
      scores had 54% lower risk of asthenozoospermia compared to those in the lowest (p
      for trend: 0.003). Being in the highest tertile of the Western pattern was
      positively associated with asthenozoospermia risk (odds ratio [OR] = 2.86; 95%
      confidence interval [CI], 1.83-2.97). CONCLUSIONS: Our findings suggest that
      adherence to the Western pattern is potentially an unfavorable indicator of
      asthenozoospermia risk and a diet composed mainly of plant-based foods may be
      associated with a reduced risk.

PMID- 25764358
TI  - The Effects of Eight-Month Physical Activity Intervention on Vigilance
      Performance in Adult Obese Population.
AB  - We aim to analyze the effects of an 8-month physical activity intervention on
      cardiorespiratory fitness, body mass index (BMI), and vigilance performance in an
      adult obese population. We conducted an 8-month physical activity intervention
      based on dance and rhythmic activities. The weekly frequency was 2 sessions of 1
      hr per day. Training sessions were divided into 3 phases: a 10-min warm-up, 40
      min of dance and rhythmic activities, and 10 min to cool-down. To assess
      cardiorespiratory fitness, participants performed a modified version of the 6-min
      walk test from the Senior Fitness Test battery (Larsson & Mattsson, 2001; Rikli &
      Jones, 1999). Vigilance performance was measured by means of the psychomotor
      vigilance task (PVT). Two measurements were performed immediately before and
      after the intervention. The results revealed that participants improved their
      cardiorespiratory fitness, BMI, and vigilance performance after the intervention.
      All in all, findings contribute new empirical evidence to the field that
      investigates the benefits of physical activity intervention on cognitive
      processes in obese population. 

PMID- 25764359
TI  - Clinical and anthropological perspectives on chemical relaxing of afro-textured
      hair.
AB  - The culturally engrained practice of 'relaxing' afro-textured hair has been
      linked with hair and scalp disorders. Herein, we discuss the evolution of human
      hair types, focusing in particular on afro-textured hair. We explore the
      biological features of this hair type, and discuss the different methods employed
      to straighten afro-textured hair, focusing in particular on chemical
      straightening. We also examine clinical, anthropological, and psychological
      issues associated with this latter practice. Examples of common scalp pathologies
      associated with chronic hair relaxing, such as alopecia, hair breakage, caustic
      burns and irritant contact dermatitis, are also highlighted. The data presented
      herein should enable clinicians to engage in culturally appropriate discussions
      with their patients about issues of appearance and conformity. 

PMID- 25764360
TI  - Influence of the artefact reduction algorithm of Picasso Trio CBCT system on the
      diagnosis of vertical root fractures in teeth with metal posts.
AB  - OBJECTIVES: To assess the influence of the artefact reduction algorithm (AR)
      available on the Picasso Trio 3D((r)) imaging system (Vatech, Hwaseong, Republic
      of Korea) on image quality [greyscale values, contrast-to-noise ratio (CNR) and
      artefact formation] and diagnosis of vertical root fractures (VRFs) in the teeth
      with intracanal metal posts. METHODS: 30 uniradicular teeth had their crowns
      removed and their roots endodontically treated to receive intracanal metal posts.
      In 20 teeth, both complete (n = 10) and incomplete (n = 10) VRFs were created.
      Each tooth was scanned twice, with and without AR activation. The mean and
      variation of greyscale values, as well as CNR, were calculated for all images.
      Subsequently, an evaluator compared the amount of artefact (cupping, white
      streaks and dark bands) in all images. Five evaluators rated for VRF presence
      using a five-point scale. RESULTS: Mean greyscale values and CNR were
      significantly decreased in images acquired with the AR. The usage of the
      algorithm promoted an overall reduction of image artefacts. Regarding the
      diagnosis of complete and incomplete VRFs, the use of the AR had an overall
      negative impact on specificity and accuracy. CONCLUSIONS: While indeed reducing
      artefact formation, the use of the AR, instead of improving the impact on the
      diagnosis of VRFs in teeth with intracanal metal posts, had a negative impact on
      the diagnosis.

PMID- 25764361
TI  - Clinical analysis of patients with primary ciliary dyskinesia in mainland China.
AB  - BACKGROUND AND AIMS: Primary ciliary dyskinesia (PCD) is a rare, genetic disorder
      featured with dysfunctional motility of cilia. Clinical presentations of PCD
      include situs inversus, repeated respiratory tract infections, otitis media,
      sinusitis and infertility. This study aims to provide clinical strategies on
      diagnosis and treatment of PCD. METHODS: Clinical data of seven patients
      diagnosed as PCD in Zhongshan Hospital, Fudan University were analyzed. We also
      extracted data from other cases in mainland China from the China Academic
      Journals Full-Text Database by the end of 2012. A total of 127 cases of PCD were
      summarized and analyzed in this study. RESULTS: Seven patients in Zhongshan
      Hospital, Fudan University were finally confirmed to have PCD. All of them had
      clinical history of recurrent respiratory infection. Imaging analysis showed
      varying degrees of bronchiectasis. Pulmonary function tests in four patients
      showed combined obstructive and restrictive patterns. Three cases were confirmed
      to have PCD by electron microscopy. We then further extracted information from
      literature for those 127 PCD patients in mainland China. All of them had chronic
      respiratory infection. Seven cases were complicated with recurrent otitis media
      and 15 cases were complicated with infertility. A total of 119 patients were
      diagnosed with situs inversus totalis (94%). Among those 127 patients, only 9
      patients' diagnosis was confirmed by electron microscopy. Four patients received
      sinus resection, and one patient received pulmonary lobectomy due to recurrent
      hemoptysis. One patient died of massive hemoptysis. CONCLUSIONS: Being a rare
      disease and easily confused with uncomplicated bronchiectasis, PCD diagnosis
      warrants particular attention. Recurrent respiratory infection, especially situs
      inversus could be the most important indicator of this disease.

PMID- 25764362
TI  - Cartilage hair hypoplasia: characteristics and orthopaedic manifestations.
AB  - PURPOSE: Cartilage hair hypoplasia (CHH) is a rare metaphyseal chondrodysplasia
      characterized by short stature and short limbs, found primarily in Amish and
      Finnish populations. Cartilage hair hypoplasia is caused by mutations in the RMRP
      gene located on chromosome 9p13.3. The disorder has several characteristic
      orthopaedic manifestations, including joint laxity, limited elbow extension,
      ankle varus, and genu varum. Immunodeficiency is of concern in most cases.
      Although patients exhibit orthopaedic problems, the orthopaedic literature on CHH
      patients is scant at best. The objective of this study was to characterize the
      orthopaedic manifestations of CHH based on the authors' unique access to the
      largest collection of CHH patients ever reported. METHODS: The authors examined
      charts and/or radiographs in 135 cases of CHH. We analyzed the orthopaedic
      manifestations to better characterize and further understand the orthopaedic
      surgeon's role in this disorder. In addition to describing the clinical
      characteristics, we report on our surgical experience in caring for CHH patients.
      RESULTS: Genu varum, with or without knee pain, is the most common reason a
      patient with CHH will seek orthopaedic consultation. Of the cases reviewed, 32
      patients had undergone surgery, most commonly to correct genu varum. CONCLUSION:
      This paper characterizes the orthopaedic manifestations of CHH. Characterizing
      this condition in the orthopaedic literature will likely assist orthopaedic
      surgeons in establishing a correct diagnosis and appreciating the orthopaedic
      manifestations. It is important that the accompanying medical conditions are
      appreciated and evaluated.

PMID- 25764363
TI  - P...N pnicogen bonds in cationic complexes of F4P+ and F3HP+ with nitrogen bases.
AB  - Ab initio MP2/aug'-cc-pVTZ calculations have been carried out on cationic
      pnicogen-bonded complexes F4P(+):N-base and F3HP(+):N-base, with linear F(ax)
      P...N and H(ax)-P...N, respectively. The bases include the sp(3)-hybridized
      nitrogen bases NH3, NClH2, NFH2, NCl2H, NCl3, NFCl2, NF2H, NF2Cl, and NF3, and
      the sp bases NCNH2, NCCH3, NP, NCOH, NCCl, NCH, NCF, NCCN, and N2. The binding
      energies of these complexes span a wide range, from -15 to -180 kJ mol(-1), as do
      the P-N distances, which vary from 1.89 to 3.11 A. There is a gap in the P-N
      distances between 2.25 and 2.53 A in which no complexes are found. Thus, the
      equilibrium complexes may be classified as inner or outer complexes based on the
      value of the P-N distance. Inner complexes have P...N bonds with varying degrees
      of covalent character, whereas outer complexes are stabilized by intermolecular
      P...N bonds with little or no covalency. Charge-transfer stabilizes these
      pnicogen-bonded complexes. For complexes F4P(+):N-base, the dominant charge
      transfer interaction is from the lone pair on N to the sigma*P-F(ax) orbital. In
      addition, there are three other charge-transfer interactions from the lone pair
      on N to the sigma*P-F(eq) orbitals, which taken together, are more stabilizing
      than the interaction involving sigma*P-F(ax). In contrast, the dominant charge
      transfer interaction for complexes F3HP(+):N-base is from the lone pair on N to
      the sigma*P-F(eq) orbitals. Computed EOM-CCSD Fermi-contact terms are excellent
      approximations to the total spin-spin coupling constants (1p)J(P-N) and (1)J(P
      H(ax)), but are poor approximations to (1)J(P-F(ax)). (1p)J(P-N) values increase
      with decreasing P-N distance, approach a maximum, and then decrease and change
      sign as the P-N distance further decreases and the pnicogen bond acquires
      increased covalency. (1)J(P-F(ax)) values for F4P(+):N-base complexes increase
      with decreasing distance. Although the P-H(ax) distance changes very little in
      complexes F3HP(+):N-base, patterns exist which suggest that changes in (1)J(P
      H(ax)) reflect the hybridization of the nitrogen base and whether the complex is
      an inner or outer complex.

PMID- 25764364
TI  - Branched artificial nanofinger arrays by mesoporous interfacial atomic
      rearrangement.
AB  - The direct production of branched semiconductor arrays with highly ordered
      orientation has proven to be a considerable challenge over the last two decades.
      Here we report a mesoporous interfacial atomic rearrangement (MIAR) method to
      directly produce highly crystalline, finger-like branched iron oxide nanoarrays
      from the mesoporous nanopyramids. This method has excellent versatility and
      flexibility for heteroatom doping of metallic elements, including Sn, Bi, Mn, Fe,
      Co, Ni, Cu, Zn, and W, in which the mesoporous nanopyramids first absorb guest
      doping molecules into the mesoporous channels and then convert the mesoporous
      pyramids into branching artificial nanofingers. The crystalline structure can
      provide more optoelectronic active sites of the nanofingers by interfacial atomic
      rearrangements of doping molecules and mesopore channels at the porous solid
      solid interface. As a proof-of-concept, the Sn-doped Fe2O3 artificial nanofingers
      (ANFs) exhibit a high photocurrent density of ~1.26 mA/cm(2), ~5.25-fold of the
      pristine mesoporous Fe2O3 nanopyramid arrays. Furthermore, with surface chemical
      functionalization, the Sn-doped ANF biointerfaces allow nanomolar level
      recognition of metabolism-related biomolecules (~5 nm for glutathione). This MIAR
      method suggests a new growth means of branched mesostructures, with enhanced
      optoelectronic applications. 

PMID- 25764366
TI  - In Silico Determination of Gas Permeabilities by Non-Equilibrium Molecular
      Dynamics: CO2 and He through PIM-1.
AB  - We study the permeation dynamics of helium and carbon dioxide through an
      atomistically detailed model of a polymer of intrinsic microporosity, PIM-1, via
      non-equilibrium molecular dynamics (NEMD) simulations. This work presents the
      first explicit molecular modeling of gas permeation through a high free-volume
      polymer sample, and it demonstrates how permeability and solubility can be
      obtained coherently from a single simulation. Solubilities in particular can be
      obtained to a very high degree of confidence and within experimental
      inaccuracies. Furthermore, the simulations make it possible to obtain very
      specific information on the diffusion dynamics of penetrant molecules and yield
      detailed maps of gas occupancy, which are akin to a digital tomographic scan of
      the polymer network. In addition to determining permeability and solubility
      directly from NEMD simulations, the results shed light on the permeation
      mechanism of the penetrant gases, suggesting that the relative openness of the
      microporous topology promotes the anomalous diffusion of penetrant gases, which
      entails a deviation from the pore hopping mechanism usually observed in gas
      diffusion in polymers. 

PMID- 25764365
TI  - The Road not Taken: Less Traveled Roads from the TGN to the Plasma Membrane.
AB  - The trans-Golgi network functions in the distribution of cargo into different
      transport vesicles that are destined to endosomes, lysosomes and the plasma
      membrane. Over the years, it has become clear that more than one transport
      pathway promotes plasma membrane localization of proteins. In spite of the
      importance of temporal and spatial control of protein localization at the plasma
      membrane, the regulation of sorting into and the formation of different transport
      containers are still poorly understood. In this review different transport
      pathways, with a special emphasis on exomer-dependent transport, and concepts of
      regulation and sorting at the TGN are discussed. 

PMID- 25764367
TI  - Changes of vision-related quality of life in retinal detachment patients after
      cataract surgery.
AB  - Rhegmatenous retinal detachment (RRD) is one of the most serious complications
      after phacoemulsification combined with intraocular lens implantation surgery. It
      has been reported that vision-related quality of life (VRQoL), as well as visual
      acuity rapidly decreased when RRD developed. However, little is known of the
      VRQoL in those RRD patients after anatomical retinal re-attachment, especially
      whether or not the VRQoL is higher than that before cataract surgery. In this
      prospective case series study, we use the Chinese-version low vision quality of
      life questionnaire (CLVQOL) to assess the changes of VRQoL in age-related
      cataract patients who suffered from RRD after phacoemulsification with
      intraocular lens (phaco-IOL) implantation. All participants were asked to
      complete questionnaires in face- to-face interviews one day before and two weeks
      after cataract surgery, as well as one day before and three months after RRD
      surgery. A total of 10,127 consecutive age-related cataract patients were
      followed up to one year after phaco-IOL implantation; among these patients, 17
      were diagnosed as RRD. The total CLVQOL scores and subscale scores except
      "Mobility" decreased significantly when RRD developed. After retinal surgery,
      only the score of "General vision and lighting" in the CLVQOL questionnaires
      improved when compared to the scores two weeks after cataract surgery, although
      the best corrected visual acuity of all patients significantly raised up.
      However, the mean CLVQOL scores and subscale scores were still considerably
      higher than the level prior to cataract surgery. Our study suggests that cataract
      patients at high risk of postoperative RRD should not deny the opportunity to
      undergo phaco-IOL implantation, even though potential VRQoL impairment induced by
      RRD exists. 

PMID- 25764368
TI  - Doctors, TV, and Truth: Evidence in the Realm of Edutainment.

PMID- 25764369
TI  - Use of Death Records to Augment Notifiable Conditions Reporting in Washington
      State.
AB  - CONTEXT: Health care providers are required to report newly diagnosed notifiable
      conditions including the case's vital status according to state regulations, but
      it is uncertain how many cases remain unreported. Death certificates could
      potentially serve as a data source for detecting unreported deaths due to
      notifiable conditions. OBJECTIVE: We sought to evaluate the usefulness of
      electronic death records to augment notifiable conditions reporting in Washington
      State. DESIGN: Cross-sectional study. SETTING: All residents of Washington State.
      PARTICIPANTS: Decedents from 2010-2012. MAIN OUTCOME MEASURES: Total number of
      fatal cases of acute infectious notifiable conditions in Washington residents
      estimated by capture-recapture analysis, proportion of estimated fatal cases
      reported to Washington's notifiable conditions database (Public Health Issue
      Management System [PHIMS]), and the proportion of estimated fatal cases
      identified solely from the death records. Information was obtained by searching
      multiple cause-of death fields on 2010-2012 death records for keywords for acute
      infectious notifiable conditions. RESULTS: Capture-recapture analysis estimated
      317 fatal cases of these conditions could be expected over the 3 years studied
      (95% CI: 276,358). Public Health Issue Management System alone identified 38% of
      total estimated cases; using PHIMS and death record data increased identification
      to 71%. Electronic filing of death records was very timely, with a median of 4
      days to visibility. Death record data were highly complete. CONCLUSIONS: Use of
      death records will augment the notifiable condition reporting system and
      potentially improve mortality estimates and disease control.

PMID- 25764371
TI  - Melatonin induces calcium mobilization and influences cell proliferation
      independently of MT1/MT2 receptor activation in rat pancreatic stellate cells.
AB  - Melatonin, the product of the pineal gland, possesses antioxidant, anti
      inflammatory, and antitumor properties in different tissues, in addition to its
      role as regulator of biological rhythms. In this study, the effects of
      pharmacological concentrations of melatonin (1 MUM-1 mM) on pancreatic stellate
      cells (PSCs) have been examined. Cell viability was studied using AlamarBlue(r)
      test. Cell-type specific markers and total amylase content were analyzed by
      immunocytochemistry and colorimetric methods, respectively. Changes in
      intracellular free Ca(2+) concentration were followed by fluorimetric analysis of
      fura-2-loaded cells. The cellular red-ox state was monitored following CM-H2DCFDA
      derived fluorescence. Determination of the activation of p44/42 mitogen-activated
      protein kinase (MAPK), SAPK/JNK and p38 was measured by Western blot analysis.
      Our results show that PSCs viability decreased in the presence of 100 MUM or 1 mM
      melatonin. However, in the presence of 1 or 10 MUM melatonin, no changes in cell
      viability were observed. Melatonin MT1 and MT2 receptors could not be detected.
      Melatonin induced Ca(2+) mobilization from intracellular pools. In the presence
      of melatonin, activation of crucial components of MAPKs pathway was noticed.
      Finally, the indole did not change the oxidative state of PSCs, but exerted a
      protective effect against H2O2-induced oxidation. We conclude that melatonin, at
      pharmacological concentrations, might regulate cellular proliferation of PSCs
      independently of specific plasma membrane receptors.

PMID- 25764370
TI  - ATPase-dependent control of the Mms21 SUMO ligase during DNA repair.
AB  - Modification of proteins by SUMO is essential for the maintenance of genome
      integrity. During DNA replication, the Mms21-branch of the SUMO pathway
      counteracts recombination intermediates at damaged replication forks, thus
      facilitating sister chromatid disjunction. The Mms21 SUMO ligase docks to the arm
      region of the Smc5 protein in the Smc5/6 complex; together, they cooperate during
      recombinational DNA repair. Yet how the activity of the SUMO ligase is controlled
      remains unknown. Here we show that the SUMO ligase and the chromosome disjunction
      functions of Mms21 depend on its docking to an intact and active Smc5/6 complex,
      indicating that the Smc5/6-Mms21 complex operates as a large SUMO ligase in vivo.
      In spite of the physical distance separating the E3 and the nucleotide-binding
      domains in Smc5/6, Mms21-dependent sumoylation requires binding of ATP to Smc5, a
      step that is part of the ligase mechanism that assists Ubc9 function. The
      communication is enabled by the presence of a conserved disruption in the coiled
      coil domain of Smc5, pointing to potential conformational changes for SUMO ligase
      activation. In accordance, scanning force microscopy of the Smc5-Mms21
      heterodimer shows that the molecule is physically remodeled in an ATP-dependent
      manner. Our results demonstrate that the ATP-binding activity of the Smc5/6
      complex is coordinated with its SUMO ligase, through the coiled coil domain of
      Smc5 and the physical remodeling of the molecule, to promote sumoylation and
      chromosome disjunction during DNA repair. 

PMID- 25764372
TI  - Ethical and practical considerations in providing critical care to patients with
      Ebola virus disease.
AB  - Infectious disease epidemics in the past have given rise to psychologic and
      emotional responses among health-care workers (HCWs), stemming from fear of
      infection during patient care. Early experiences in the AIDS epidemic provide an
      example where fear of contagion resulted in differential treatment of patients
      infected with HIV. However, with a deeper understanding of AIDS pathogenesis and
      treatment, fear and discrimination diminished. Parallels exist between early
      experiences with AIDS and the present outbreak of Ebola virus disease in West
      Africa, particularly regarding discussions of medical futility in seriously ill
      patients. We provide a historical perspective on HCWs' risk of infection during
      the provision of CPR, discuss physicians' duty to treat in the face of perceived
      or actual HCW risk, and, finally, present the protocols implemented at the
      National Institutes of Health to reduce HCW risk while providing lifesaving and
      life-sustaining care.

PMID- 25764373
TI  - Chemical synthesis of the outer core oligosaccharide of Escherichia coli R3 and
      immunological evaluation.
AB  - Lipopolysaccharides (LPS), major virulence determinants in Gram-negative
      bacteria, are responsible for many pathophysiological responses and can elicit
      strong immune responses. In order to better understand the role of LPS in host
      pathogen interactions and elucidate the immunogenic properties of LPS outer core
      oligosaccharides, an all alpha-linked Escherichia coli R3 outer core
      pentasaccharide was first synthesized with a propyl amino linker at the reducing
      end. This oligosaccharide was also covalently conjugated to a carrier protein
      (CRM197) via the reducing end propyl amino linker. Immunological analysis
      demonstrated that this glycoconjugate can elicit specific anti-pentasaccharide
      antibodies with in vitro bactericidal activity. These findings will contribute to
      the further exploration of this pentasaccharide antigen as a vaccine candidate. 

PMID- 25764374
TI  - Gold nanoisland films as reproducible SERS substrates for highly sensitive
      detection of fungicides.
AB  - A wet-chemical approach is used to fabricate centimeter-scale gold nanoisland
      films (NIFs) with tunable morphology of islands and with strong electromagnetic
      coupling between them. The approach consists in a uniform seeding of small gold
      nanoparticles on a glass or silicon substrate, followed by controllable growth of
      the seeds into small nanoislands. A special technique for TEM sampling was
      developed to follow the gradual formation of larger-sized isolated nanoparticles,
      nanoislands of sintered overgrown seeds, and a complete gold layer with nanoscale
      cracks. The electromagnetic field distribution inside the fabricated NIFs was
      calculated by FDTD simulations applied to actual TEM images of the fabricated
      samples rather than to artificial models commonly used. SERS measurements with
      1,4-aminothiophenol (ATP) molecules demonstrated the analytical enhancement
      factor about of 10(7) and the fundamental enhancement factor about of 10(8) for
      optimized substrates. These values were at least 1 order of magnitude higher than
      that for self-assembled arrays of gold nanostars and silver nanocubes. SERS
      spectra of independent samples demonstrated good sample-to-sample reproducibility
      in terms of the relative standard deviation (RSD) of the main peaks less than
      20%. Additionally, Raman maps with 1 MUm increment in X-Y directions of NIFs (800
      spectral spots) demonstrated good point-to-point repeatability in the intensity
      of the main Raman vibration modes (RSD varied from 5% to 15% for 50 randomly
      selected points). A real-life application of the fabricated SERS substrates is
      exemplified by the detection of the thiram fungicide in apple peels within the 5
      250 ppb linear detection range. Specifically, the NIF-based SERS technology
      detected thiram on apple peel down to level of 5 ng/cm(2). 

PMID- 25764376
TI  - Randomized clinical trial of laparoscopic colectomy with or without natural
      orifice specimen extraction.
AB  - BACKGROUND: Although conventional laparoscopic colectomy is a validated
      technique, laparoscopic natural-orifice specimen extraction (NOSE) colectomy
      might improve outcome. This randomized clinical trial compared analgesia
      requirements, postoperative pain, anorectal function, inflammatory response and
      cosmesis in laparoscopic NOSE colectomy and conventional laparoscopic colectomy.
      METHODS: Patients were randomly assigned to undergo laparoscopic NOSE colectomy
      or conventional laparoscopic colectomy for left-sided colonic disease. The
      primary endpoint was analgesia requirement. Secondary endpoints were operative
      outcome, inflammatory response, anorectal function and cosmesis. RESULTS: Forty
      patients were enrolled in the study, 20 in each group (15 with diverticulitis and
      5 with colorectal cancer in each group). A significant difference was observed in
      morphine analogue requirements (1 of 20 patients in the NOSE group versus 10 of
      20 in the conventional group; P = 0.003). Patient-controlled epidural analgesia
      was lower in the NOSE group (mean 116 ml versus 221 ml in the conventional group;
      P < 0.001), as was paracetamol use (mean 11.0 versus 17.0 g respectively; P <
      0.001). Postoperative pain scores were lower in the NOSE group: mean maximum
      visual analogue score of 3.5 versus 2.1 (P < 0.001). One week after hospital
      discharge, pain scores remained higher in the conventional group: 15 of 20
      patients in the conventional group reported pain, compared with one of 20 in the
      NOSE group (P < 0.001). Inflammatory responses were greater in patients
      undergoing NOSE colectomy: higher peak C-reactive protein and interleukin 6
      levels were observed on postoperative day 2 (P < 0.001) and day 1 (P = 0.002)
      respectively. Postoperative anorectal function, complications and hospital stay
      were similar in the two groups. CONCLUSION: Laparoscopic NOSE colectomy was
      associated with less pain and lower analgesia requirements than the conventional
      laparoscopic extraction. REGISTRATION NUMBER: NCT01033838
      (http://www.clinicaltrials.gov).

PMID- 25764377
TI  - Iodine status of Eeyou Istchee community members of northern Quebec, Canada, and
      potential sources.
AB  - A multi community environment-and-health study among six of the nine communities
      of Eeyou Istchee in northern Quebec, Canada provided greater insight into iodine
      intake levels among these Cree First Nation communities. Using data from this
      large population-based study, descriptive statistics of measured urinary iodine
      concentrations (UICs) and iodine-creatinine ratios (stratified by age, sex,
      community of residence, and water consumption) were calculated, and the
      associations between independent variables and iodine concentration measures were
      examined through a general linear model. Traditional food consumption
      contributions were examined through Pearson partial correlation tests and linear
      regression analyses; and the importance of water sources through ANOVA. Generally
      speaking, urinary iodine levels of Eeyou Istchee community members were within
      the adequate range set out by the World Health Organization, though sex and
      community differences existed. However, men in one community were considered to
      be at risk of iodine deficiency. Older participants had significantly higher mean
      iodine-creatinine ratios than younger participants (15-39 years = 90.50 MUmol
      mol(-1); >39 years = 124.52 MUmol mol(-1)), and consumption of beaver (Castor
      canadensis) meat, melted snow and ice, and bottled water were predictive of
      higher iodine excretion. It is concluded that using both urinary iodine
      indicators can be helpful in identifying subgroups at greater risk of iodine
      deficiency. 

PMID- 25764378
TI  - Development and validation of a HPLC method using a monolithic column for
      quantification of trans-resveratrol in lipid nanoparticles for intestinal
      permeability studies.
AB  - The development of nanodelivery systems that protect trans-resveratrol is
      extremely important to preserve its bioactive properties in the development of
      further applications as nutraceuticals to supplement foods and beverages. In this
      work, a validated HPLC method was developed for the quantification of trans
      resveratrol in lipid nanoparticles for application in studies of in vitro
      intestinal permeability. The chromatographic separation was achieved in a C18
      monolithic column connected to a fluorometric detector (330/374 nm), by isocratic
      elution consisting of 2% acetic acid/acetonitrile (80:20). Two calibration ranges
      were established (0.020-0.200 and 0.200-2.00 MUmol L(-1)), and low quantification
      limits (2-6 nmol L(-1), 23-69 pg) were achieved. Stability studies showed that
      trans-resveratrol is stable for 24 h at 4  degrees C, and storage at room
      temperature and freeze-thaw cycles are not recommended. The proposed method was
      applied to in vitro intestinal permeability studies, in which values between 0.05
      +/- 0.01 and 1.8 +/- 0.3 MUmol L(-1) were found.

PMID- 25764379
TI  - Femtosecond cooling of hot electrons in CdSe quantum-well platelets.
AB  - Semiconductor quantum wells are ubiquitous in high-performance optoelectronic
      devices such as solar cells and lasers. Understanding and controlling of the
      (hot) carrier dynamics is essential to optimize their performance. Here, we study
      hot electron cooling in colloidal CdSe quantum-well nanoplatelets using ultrafast
      two-photon photoemission spectroscopy at low excitation intensities, resulting
      typically in 1-5 hot electrons per platelet. We observe initial electron cooling
      in the femtosecond time domain that slows down with decreasing electron energy
      and is finished within 2 ps. The cooling is considerably faster at cryogenic
      temperatures than at room temperature, and at least for the systems that we
      studied, independent of the thickness of the platelets (here 3-5 CdSe units) and
      the presence of a CdS shell. The cooling rates that we observe are orders of
      magnitude faster than reported for similar CdSe platelets under strong
      excitation. Our results are understood by a classic cooling mechanism with
      emission of longitudinal optical phonons without a significant influence of the
      surface. 

PMID- 25764383
TI  - Erratum.

PMID- 25764384
TI  - Broadbent et al. respond.

PMID- 25764380
TI  - Genome-wide detection of allelic genetic variation to predict biochemical
      recurrence after radical prostatectomy among prostate cancer patients using an
      exome SNP chip.
AB  - PURPOSES: Genetic variations among prostate cancer patients who underwent radical
      prostatectomies were evaluated to predict biochemical recurrence, and used to
      develop a clinical-genetic model that combines data on clinicopathological
      factors of prostate cancer and individual genetic variations. MATERIALS AND
      METHODS: We genotyped 242,186 SNPs on a custom HumanExome BeadChip v1.0
      (Illuminam Inc.) from the blood DNA of 776 PCa patients who underwent radical
      prostatectomy. Genetic data were analyzed to calculate an odds ratio as an
      estimate of the relative risk of biochemical recurrence. And we compared
      accuracies from the multivariate model incorporating clinicopathological factors
      between included and excluded selected lead single nucleotide polymorphisms.
      Biochemical recurrence-free survival outcomes also analyzed using these genetic
      variations. RESULTS: Genetic array analysis indicated that eight single
      nucleotide polymorphisms (rs77080351, rs200944490, rs2071292, rs117237810,
      rs191118242, rs4965121, rs61742396, and rs6573513) were significant to predict
      biochemical recurrence after radical prostatectomy. When a multivariate model
      incorporating clinicopathological factors was devised to predict biochemical
      recurrence, the predictive accuracy of model was 85.1 %. By adding in two
      individual variations of single nucleotide polymorphisms in the multivariate
      model, the predictive accuracy increased to 87.7 % (P = 0.045). With three
      variations of single nucleotide polymorphisms, the predictive accuracy further
      improved to 89.0 % (P = 0.025). These genetic variations had a significantly
      decreased biochemical recurrence-free survival rate. CONCLUSIONS: Based on exome
      array, the selected single nucleotide polymorphisms were predictors for
      biochemical recurrence. The addition of individualized genetic information
      effectively enhanced the predictive accuracy of biochemical recurrence among
      prostate cancer patients who underwent radical prostatectomy.

PMID- 25764385
TI  - CO2 sorption kinetics of scaled-up polyethylenimine-functionalized mesoporous
      silica sorbent.
AB  - Two CO2 solid sorbents based on polyethylenimine, PEI (M(n) ~ 423 and 10K),
      impregnated into mesoporous silica (MPS) foam prepared in kilogram quantities via
      a scale-up process were synthesized and systematically characterized by a range
      of analytical and surface techniques. The mesoporous silica sorbent impregnated
      with lower molecular weight PEI, PEI-423/MPS, showed higher capacity toward CO2
      sorption than the sorbent functionalized with the higher molecular weight PEI
      (PEI-10K/MPS). On the other hand, PEI-10K/MPS exhibited higher thermal stability
      than PEI-423/MPS. The kinetics of CO2 adsorption on both PEI/MPS fitted well with
      a double-exponential model. According to this model CO2 adsorption can be divided
      into two steps: the first is fast and is attributed to CO2 adsorption on the
      sorbent surface; the second is slower and can be related to the diffusion of CO2
      within and between the mesoporous particles. In contrast, the desorption process
      obeyed first-order kinetics with activation energies of 64.3 and 140.7 kJ mol(-1)
      for PEI-423/MPS and PEI-10K/MPS, respectively. These studies suggest that the
      selection of amine is critical as it affects not only sorbent capacity and
      stability but also the energy penalty associated with sorbent regeneration.

PMID- 25764386
TI  - Shakespeare in Prison: affecting health and wellbeing.
AB  - PURPOSE: This research aimed to investigate the impacts of the Queensland
      Shakespeare Ensemble Prison Project (QSEPP) on the health and wellbeing of
      participants, specifically with regard to social support.
      DESIGN/METHODOLOGY/APPROACH: Semi-structured interviews were conducted with
      prisoners participating in the project to gain insight into perceived sense of
      support within the QSEPP and across the prison context more broadly. FINDINGS:
      The QSEPP encouraged participants to foster a range of support networks through
      the development of relationships built on trust, respect and shared experiences.
      Participants also developed communication skills which may assist with
      establishing and maintaining supportive relationships inside and outside of
      prison. RESEARCH LIMITATIONS/IMPLICATIONS: This research highlights the
      inevitable challenges for researchers working within the prison context,
      including: correctional services' limitations, time and space restrictions and
      small sample sizes. This research offers some potentially innovative ways to
      combat such challenges. PRACTICAL IMPLICATIONS: The study highlights the
      potential of theatre-based interventions in the prison context and their role in
      fostering social support and enhancing wellbeing. SOCIAL IMPLICATIONS: The
      research explores the potential role theatre may play in improving the health and
      wellbeing of a disadvantaged and marginalised group, providing skills to enhance
      access to supportive networks inside and outside prison. ORIGINALITY/VALUE: To
      the best of our knowledge this is the first research of its kind and provides
      valuable insights into the role that theatre may play in fostering social support
      in the prison context.

PMID- 25764387
TI  - Incarcerated women develop a nutrition and fitness program: participatory
      research.
AB  - PURPOSE: Women in prison throughout the world experience higher rates of mental
      and physical illness compared with the general population and compared with men
      in prison. The paper finds no published studies that report on men or women in
      prison engaging in participatory health research to address their concerns about
      nutrition and fitness. The purpose of this paper is to describe a pilot nutrition
      and fitness program, which resulted from a unique prison participatory health
      research project. DESIGN/METHODOLOGY/APPROACH: Women in prison designed, led, and
      evaluated a six-week pilot fitness program in a minimum/medium security women's
      prison. Pre- and post-program assessments included a self-administered
      questionnaire and body measures. Open-ended questionnaire responses illuminated
      the quantitative findings. FINDINGS: Sixteen women in prison completed the
      program evaluation. Weight, body mass index, waist-to-hip ratio, and chest
      measurements decreased, and energy, sleep, and stress levels improved by the end
      of the program. RESEARCH LIMITATIONS/IMPLICATIONS: As a component of a
      participatory research project, incarcerated women designed and led a nutrition
      and fitness program, which resulted in improved body measures and self-reported
      health benefits. ORIGINALITY VALUE: Incarceration provides opportunities to
      engage women in designing their own health programs with consequent potential
      long-term "healing" benefits.

PMID- 25764388
TI  - Health promotion and young prisoners: a European perspective.
AB  - PURPOSE: The purpose of this paper is to assess the health promotion needs of
      vulnerable young prisoners and the existing health promotion activities in
      custodial settings in seven European Union (EU) Member States.
      DESIGN/METHODOLOGY/APPROACH: The research comprised two components: the first
      involved identifying existing health promotion practices. The second involved
      mapping out young offenders' health promotion needs by carrying out a needs
      assessment. Both quantitative and qualitative methods were adopted. The
      quantitative element comprised surveys among young prisoners and prison staff and
      focused on the availability and perceived importance of health promotion
      activities in prison. The qualitative element comprised focus groups with young
      offenders and individual interviews with prison staff, field experts and NGO
      members. FINDINGS: The findings from the research have identified a number of
      similar, but also some diverse areas of unmet need for health promotion
      activities in prison settings across these diverse seven EU countries. There is
      no consistency of approach within and between countries regarding health
      promotion policy, guidance, resources and programmes for young prisoners. In
      order to improve the health of young prisoners and to establish and increase
      sustainability of existing health promotion programmes, there is a need for the
      establishment of National and EU standards. ORIGINALITY/VALUE: Providing health
      promotion activities for young prisoners while in custodial settings is key to
      addressing their unmet health and well-being needs and to facilitate their
      reintegration back into the community. Despite the barriers identified by this
      research, health promotion is to some extent being delivered in the partner
      countries and provides a foundation upon which further implementation of health
      promotion activities can be built especially when the benefits of health
      promotion activities, like dealing with the common problems of alcohol and drug
      addiction, mental health and communicable diseases are linked to successful
      reintegration.

PMID- 25764389
TI  - Cyclodextrins in Food Technology and Human Nutrition: Benefits and Limitations.
AB  - Cyclodextrins are tasteless, odorless, nondigestible, noncaloric, noncariogenic
      saccharides, which reduce the digestion of carbohydrates and lipids. They have
      low glycemic index and decrease the glycemic index of the food. They are either
      non- or only partly digestible by the enzymes of the human gastrointestinal (GI)
      tract and fermented by the gut microflora. Based on these properties,
      cyclodextrins are dietary fibers useful for controlling the body weight and blood
      lipid profile. They are prebiotics, improve the intestinal microflora by
      selective proliferation of bifidobacteria. These antiobesity and anti-diabetic
      effects make them bioactive food supplements and nutraceuticals. In this review,
      these features are evaluated for alpha-, beta- and gamma-cyclodextrins, which are
      the cyclodextrin variants approved by authorities for food applications. The
      mechanisms behind these effects are reviewed together with the applications as
      solubilizers, stabilizers of dietary lipids, such as unsaturated fatty acids,
      phytosterols, vitamins, flavonoids, carotenoids and other nutraceuticals. The
      recent applications of cyclodextrins for reducing unwanted components, such as
      trans-fats, allergens, mycotoxins, acrylamides, bitter compounds, as well as in
      smart active packaging of foods are also overviewed. 

PMID- 25764390
TI  - Diagnosis and assessment of peripheral arterial disease in the diabetic foot.
AB  - Approximately half of all patients with a diabetic foot ulcer have co-existing
      peripheral arterial disease. Identifying peripheral arterial disease among
      patients with foot ulceration is important, given its association with failure to
      heal, amputation, cardiovascular events and increased risk of premature
      mortality. Infection, oedema and neuropathy, often present with ulceration, may
      adversely affect the performance of diagnostic tests that are reliable in
      patients without diabetes. Early recognition and expert assessment of peripheral
      arterial disease allows measures to be taken to reduce the risk of amputation and
      cardiovascular events, while determining the need for revascularization to
      promote ulcer healing. When peripheral arterial disease is diagnosed, the extent
      of perfusion deficit should be measured. Patients with a severe perfusion
      deficit, likely to affect ulcer healing, will require further imaging to define
      the anatomy of disease and indicate whether a revascularization procedure is
      appropriate. 

PMID- 25764392
TI  - Erratum to: Abiotic Photophosphorylation Model Based on Abiogenic Flavin and
      Pteridine Pigments.

PMID- 25764391
TI  - "It's All About the Body": The Bodily Capital of Armed Response Officers in South
      Africa.
AB  - In this article, I analyze the role of bodily capital in the daily policing
      practices of armed response officers, a specific type of private security
      officers, in Durban, South Africa. Based on 20 months of ethnographic fieldwork,
      I argue that the masculinized bodily capital of armed response officers is a key
      source of their sovereign power; it plays a central role in how they acquire and
      exert authority. Furthermore, I argue that an analysis of bodily capital should
      not solely analyze the actual flesh of the body, but must include particular
      equipment (such as bulletproof vests and firearms) that is experienced as a part
      of the body. 

PMID- 25764393
TI  - Effects of inorganic nitrate and beetroot supplementation on endothelial
      function: a systematic review and meta-analysis.
AB  - BACKGROUND: Diets rich in inorganic nitrate are associated with lower blood
      pressure, an effect that may be mediated by an improvement of endothelial
      function (EF). Therefore, a systematic review and meta-analysis of randomised
      controlled trials (RCTs) were conducted to examine the effects of inorganic
      nitrate and beetroot supplementation on measures of EF. METHODS: MEDLINE, EMBASE
      and Scopus databases were searched from inception until November 2014. Specific
      inclusion criteria were as follows: (1) RCTs; (2) trials comparing inorganic
      nitrate or beetroot supplementation with placebo control groups; and (3) trials
      reporting effects of these interventions on outcomes of vascular function. Random
      effect models were used to assess the pooled effect sizes showed as standardised
      mean differences (SMD). RESULTS: Nine crossover trials and three parallel trials
      met our inclusion criteria. The trials were conducted between 2008 and 2014 and
      included a total of 246 participants with 10-64 participants per study. The
      duration of each intervention ranged from 1.5 h to 28 days. Inorganic nitrate and
      beetroot consumption was associated with an improvement in vascular function (SMD
      0.36; 95 % CI 0.16, 0.56; P < 0.001). The effect on EF was significantly
      associated with the dose of inorganic nitrate (beta = 0.04, SE = 0.01, P <
      0.001), age (beta = -0.01, SE = 0.004, P = 0.02), baseline BMI (beta = -0.04, SE
      = 0.02, P = 0.05) and systolic BP (beta = -0.01, SE = 0.005, P = 0.02).
      CONCLUSIONS: Inorganic nitrate and beetroot supplementation was associated with
      beneficial effects on EF. These effects appear to be reduced in older subjects
      and in subjects with greater cardiometabolic risk.

PMID- 25764394
TI  - The role of pre-transplant induction regimens and autologous stem cell
      transplantation in the era of novel targeted agents.
AB  - Outcome of patients with multiple myeloma (MM) has greatly improved with the use
      of autologous stem cell transplantation (ASCT) and new agents, such as
      immunomodulatory drugs (thalidomide and lenalidomide) and proteasome inhibitors
      (bortezomib). When compared to conventional chemotherapy, high-dose melphalan
      with ASCT significantly improved response rates and progression-free survival,
      while overall survival benefit was not consistent across all trials. ASCT is
      considered the standard treatment for patients who are younger than 65 years and
      who do not have limiting comorbidities. New, effective agents have been
      introduced as part of induction, consolidation and maintenance treatments within
      ASCT and in combinations with chemotherapy for patients not eligible for ASCT.
      The remarkable results obtained with these regimens are questioning the role of
      ASCT for newly diagnosed MM patients. This article aims to delineate the role of
      ASCT in the era of novel agents based on the results of recent clinical trials. 

PMID- 25764395
TI  - Midgut volvulus as initial presentation of pneumatosis cystoides intestinalis.

PMID- 25764396
TI  - Use of time-resolved fluorescence spectroscopy to evaluate diagnostic value of
      collagen degradation products.
AB  - The concentration of collagen degradation products (CDPs) may reflect the process
      of left ventricular remodeling (LVR). The aim of this study was to evaluate the
      potential diagnostic usefulness of time-resolved fluorescence spectroscopy (TRFS)
      in assessment of CDPs. The preliminary experiment was designed to establish if
      CDPs' characteristics might be visible by mean fluorescence lifetime (FLT) in
      determined conditions. The in vitro model of CDPs was prepared by conducting the
      hydrolysis of type III collagen. The FLT of samples was measured by the time
      resolved spectrometer Life Spec II with the subnanosecond pulsed 360-nm EPLED
      diode. The FLTs were obtained by deconvolution analysis of the data using a
      multiexponential model of fluorescence decay. In order to determine the limit of
      traceability of CDPs, a comparison of different collagen/plasma ratio in samples
      was performed. The results of our study showed that the increase of added plasma
      to hydrolyzed collagen extended the mean FLT. Thus, the diagnosis of LVR based on
      measurements using TRFS is possible. However, it is important to point out the
      experiment was preliminary and further investigation in this field of research is
      crucial.

PMID- 25764397
TI  - Impaired systemic tetrahydrobiopterin bioavailability and increased
      dihydrobiopterin in adult falciparum malaria: association with disease severity,
      impaired microvascular function and increased endothelial activation.
AB  - Tetrahydrobiopterin (BH4) is a co-factor required for catalytic activity of
      nitric oxide synthase (NOS) and amino acid-monooxygenases, including
      phenylalanine hydroxylase. BH4 is unstable: during oxidative stress it is non
      enzymatically oxidized to dihydrobiopterin (BH2), which inhibits NOS. Depending
      on BH4 availability, NOS oscillates between NO synthase and NADPH oxidase: as the
      BH4/BH2 ratio decreases, NO production falls and is replaced by superoxide. In
      African children and Asian adults with severe malaria, NO bioavailability
      decreases and plasma phenylalanine increases, together suggesting possible BH4
      deficiency. The primary three biopterin metabolites (BH4, BH2 and B0 [biopterin])
      and their association with disease severity have not been assessed in falciparum
      malaria. We measured pterin metabolites in urine of adults with severe falciparum
      malaria (SM; n=12), moderately-severe malaria (MSM, n=17), severe sepsis (SS;
      n=5) and healthy subjects (HC; n=20) as controls. In SM, urinary BH4 was
      decreased (median 0.16 1/4mol/mmol creatinine) compared to MSM (median 0.27), SS
      (median 0.54), and HC (median 0.34)]; p<0.001. Conversely, BH2 was increased in
      SM (median 0.91 1/4mol/mmol creatinine), compared to MSM (median 0.67), SS
      (median 0.39), and HC (median 0.52); p<0.001, suggesting increased oxidative
      stress and insufficient recycling of BH2 back to BH4 in severe malaria. Overall,
      the median BH4/BH2 ratio was lowest in SM [0.18 (IQR: 0.04-0.32)] compared to MSM
      (0.45, IQR 0.27-61), SS (1.03; IQR 0.54-2.38) and controls (0.66; IQR 0.43-1.07);
      p<0.001. In malaria, a lower BH4/BH2 ratio correlated with decreased
      microvascular reactivity (r=0.41; p=0.03) and increased ICAM-1 (r=-0.52;
      p=0.005). Decreased BH4 and increased BH2 in severe malaria (but not in severe
      sepsis) uncouples NOS, leading to impaired NO bioavailability and potentially
      increased oxidative stress. Adjunctive therapy to regenerate BH4 may have a role
      in improving NO bioavailability and microvascular perfusion in severe falciparum
      malaria.

PMID- 25764398
TI  - Resilience Is Associated with Outcome from Mild Traumatic Brain Injury.
AB  - Resilient individuals manifest adaptive behavior and are better able to recover
      from adversity. The association between resilience and outcome from mild
      traumatic brain injury (mTBI) is examined, and the reliability and validity of
      the Resilience Scale and its short form in mTBI research is evaluated. Patients
      with mTBI (n=74) and orthopedic controls (n=39) completed the Resilience Scale at
      one, six, and 12 months after injury. Additionally, self-reported post-concussion
      symptoms, fatigue, insomnia, pain, post-traumatic stress, and depression, as well
      as quality of life, were evaluated. The internal consistency of the Resilience
      Scale and the short form ranged from 0.91 to 0.93 for the mTBI group and from
      0.86 to 0.95 for controls. The test-retest reliability ranged from 0.70 to 0.82.
      Patients with mTBI and moderate-to-high resilience reported significantly fewer
      post-concussion symptoms, less fatigue, insomnia, traumatic stress, and
      depressive symptoms, and better quality of life, than the patients with low
      resilience. No association between resilience and time to return to work was
      found. Resilience was associated with self-reported outcome from mTBI, and based
      on this preliminary study, can be reliably evaluated with Resilience Scale and
      its short form in those with mTBIs. 

PMID- 25764400
TI  - Ischaemic conditioning: intervening to protect; before, after, and at a distance.

PMID- 25764399
TI  - Factors associated with severe human Rift Valley fever in Sangailu, Garissa
      County, Kenya.
AB  - BACKGROUND: Mosquito-borne Rift Valley fever virus (RVFV) causes acute, often
      severe, disease in livestock and humans. To determine the exposure factors and
      range of symptoms associated with human RVF, we performed a population-based
      cross-sectional survey in six villages across a 40 km transect in northeastern
      Kenya. METHODOLOGY/PRINCIPAL FINDINGS: A systematic survey of the total
      populations of six Northeastern Kenyan villages was performed. Among 1082
      residents tested via anti-RVFV IgG ELISA, seroprevalence was 15% (CI95%, 13-17%).
      Prevalence did not vary significantly among villages. Subject age was a
      significant factor, with 31% (154/498) of adults seropositive vs. only 2% of
      children <=15 years (12/583). Seroprevalence was higher among men (18%) than
      women (13%). Factors associated with seropositivity included a history of animal
      exposure, non-focal fever symptoms, symptoms related to meningoencephalitis, and
      eye symptoms. Using cluster analysis in RVFV positive participants, a more severe
      symptom phenotype was empirically defined as having somatic symptoms of acute
      fever plus eye symptoms, and possibly one or more meningoencephalitic or
      hemorrhagic symptoms. Associated with this more severe disease phenotype were
      older age, village, recent illness, and loss of a family member during the last
      outbreak. In multivariate analysis, sheltering livestock (aOR = 3.5 CI95% 0.93
      13.61, P = 0.065), disposing of livestock abortus (aOR = 4.11, CI95% 0.63-26.79,
      P = 0.14), and village location (P = 0.009) were independently associated with
      the severe disease phenotype. CONCLUSIONS/SIGNIFICANCE: Our results demonstrate
      that a significant proportion of the population in northeastern Kenya has been
      infected with RVFV. Village and certain animal husbandry activities were
      associated with more severe disease. Older age, male gender, herder occupation,
      killing and butchering livestock, and poor visual acuity were useful markers for
      increased RVFV infection. Formal vision testing may therefore prove to be a
      helpful, low-technology tool for RVF screening during epidemics in high-risk
      rural settings.

PMID- 25764401
TI  - Emergence delirium in children.

PMID- 25764402
TI  - 'From darkness into light': time to make awake intubation with videolaryngoscopy
      the primary technique for an anticipated difficult airway?

PMID- 25764403
TI  - Fibreoptic vs videolaryngoscopic (C-MAC((r)) D-BLADE) nasal awake intubation
      under local anaesthesia.
AB  - Numerous indirect laryngoscopes have been introduced into clinical practice and
      their use for tracheal intubation under local anaesthesia has been described.
      However, a study comparing indirect laryngoscopic vs fibreoptic intubation under
      local anaesthesia and sedation appears lacking. Therefore, we evaluated both
      techniques in 100 patients with an anticipated difficult nasal intubation time
      for intubation the primary outcome. We also assessed success rate, glottic view,
      Ramsey score, and patients' and anaesthetists' satisfaction. The median (IQR
      [range]) time for intubation was significantly shorter with the videolaryngoscope
      with 38 (24-65 [11-420]) s vs 94 (48-323 [19-1020]) s (p < 0.0001). There was no
      difference in the success rate of intubation (96% for both techniques; p >
      0.9999) and satisfaction of the anaesthetists and patients. We conclude that in
      anticipated difficult nasal intubation a videolaryngoscope represents an
      acceptable alternative to fibreoptic intubation.

PMID- 25764405
TI  - A systematic review of pre-operative anaemia and blood transfusion in patients
      with fractured hips.
AB  - We systematically reviewed the observational associations of anaemia with
      outcomes and the effects of interventions to increase haemoglobin concentrations
      following hip fracture in older people. Anaemia on hospital admission was
      associated with increased mortality, relative risk 1.64 (95% CI 1.47-1.82), p <
      0.0001. After adjustment for co-morbidities, the association of anaemia with
      increased mortality remained in four of eight observational studies. There was no
      association of postoperative transfusion with mortality after adjusting for
      covariates. Transfusion at 80 g.l(-1) vs 100 g.l(-1) increased acute myocardial
      infarction, relative risk 1.67 (95% CI 1.01-2.77), p = 0.05. Transfusion
      threshold was not associated with differences in other outcomes. There were
      insufficient high-quality studies to inform pre-operative blood transfusion or
      the use of peri-operative iron or erythropoietin. Studies for most interventions
      recruited too few participants to determine effects on infections, mortality or
      function.

PMID- 25764406
TI  - Snail trail.

PMID- 25764404
TI  - Peri-operative anaesthetic myocardial preconditioning and protection - cellular
      mechanisms and clinical relevance in cardiac anaesthesia.
AB  - Preconditioning has been shown to reduce myocardial damage caused by ischaemia
      reperfusion injury peri-operatively. Volatile anaesthetic agents have the
      potential to provide myocardial protection by anaesthetic preconditioning and, in
      addition, they also mediate renal and cerebral protection. A number of proof-of
      concept trials have confirmed that the experimental evidence can be translated
      into clinical practice with regard to postoperative markers of myocardial injury;
      however, this effect has not been ubiquitous. The clinical trials published to
      date have also been too small to investigate clinical outcome and mortality. Data
      from recent meta-analyses in cardiac anaesthesia are also not conclusive
      regarding intra-operative volatile anaesthesia. These inconclusive clinical
      results have led to great variability currently in the type of anaesthetic agent
      used during cardiac surgery. This review summarises experimentally proposed
      mechanisms of anaesthetic preconditioning, and assesses randomised controlled
      clinical trials in cardiac anaesthesia that have been aimed at translating
      experimental results into the clinical setting. 

PMID- 25764407
TI  - Time for mandatory colour coding of drug ampoules and packaging - yet again.

PMID- 25764408
TI  - A reply from the AAGBI.

PMID- 25764409
TI  - UK survey of skin antisepsis for neuraxial block.

PMID- 25764410
TI  - Cricoid cartilage compression devices.

PMID- 25764411
TI  - Regional service evaluation of echocardiography trainers.

PMID- 25764412
TI  - Clarifying the indications for difficult airway alert forms.

PMID- 25764413
TI  - Laryngeal cuff pressure - an equilibrium recoil technique.

PMID- 25764414
TI  - Death of the anaesthetic room I.

PMID- 25764415
TI  - Death of the anaesthetic room II.

PMID- 25764416
TI  - Yet more on Pecs block nomenclature.

PMID- 25764417
TI  - Joseph Snape and electroanaesthesia.

PMID- 25764418
TI  - A reply.

PMID- 25764419
TI  - Amplified somatosensory and visual cortical projections to a core auditory area,
      the anterior auditory field, following early- and late-onset deafness.
AB  - Cross-modal reorganization following the loss of input from a sensory modality
      can recruit sensory-deprived cortical areas to process information from the
      remaining senses. Specifically, in early-deaf cats, the anterior auditory field
      (AAF) is unresponsive to auditory stimuli but can be activated by somatosensory
      and visual stimuli. Similarly, AAF neurons respond to tactile input in adult
      deafened animals. To examine anatomical changes that may underlie this functional
      adaptation following early or late deafness, afferent projections to AAF were
      examined in hearing cats, and cats with early- or adult-onset deafness.
      Unilateral deposits of biotinylated dextran amine were made in AAF to
      retrogradely label cortical and thalamic afferents to AAF. In early-deaf cats,
      ipsilateral neuronal labeling in visual and somatosensory cortices increased by
      329% and 101%, respectively. The largest increases arose from the anterior
      ectosylvian visual area and the anterolateral lateral suprasylvian visual area,
      as well as somatosensory areas S2 and S4. Consequently, labeling in auditory
      areas was reduced by 36%. The age of deafness onset appeared to influence
      afferent connectivity, with less marked differences observed in late-deaf cats.
      Profound changes to visual and somatosensory afferent connectivity following
      deafness may reflect corticocortical rewiring affording acoustically deprived AAF
      with cross-modal functionality.

PMID- 25764420
TI  - Post-translational regulation of SHORT VEGETATIVE PHASE as a major mechanism for
      thermoregulation of flowering.
AB  - In contrast to our extensive knowledge of vernalization, we know relatively
      little about the regulation of ambient temperature-responsive flowering. Recent
      reports revealed that FLOWERING LOCUS M (FLM) and SHORT VEGETATIVE PHASE (SVP)
      regulate high ambient temperature-responsive flowering through two different
      mechanisms: degradation of SVP protein and formation of a non-functional SVP-FLM
      delta complex. To investigate further the mechanism of thermoregulation of
      flowering, we performed real-time quantitative polymerase chain reaction (RT
      qPCR) and in vitro pull-down assays. We found that FLM-beta and FLM-delta
      transcripts show similar absolute levels at different temperatures. Also, His-SVP
      protein bound to the GST-FLM-beta or -delta proteins with similar binding
      intensities. These results suggest that functional SVP-FLM-beta and non
      functional SVP-FLM-delta complexes form similarly at warmer temperatures, thus
      indicating that post-translational regulation of SVP functions as a major
      mechanism for thermoregulation in flowering. 

PMID- 25764421
TI  - Phylogenetic analysis of the expansion of the MATH-BTB gene family in the
      grasses.
AB  - MATH-BTB proteins are known to act as substrate-specific adaptors of cullin3
      (CUL3)-based ubiquitin E3 ligases to target protein for ubiquitination. In a
      previous study we reported the presence of 31 MATH-BTB genes in the maize genome
      and determined the regulatory role of the MATH-BTB protein MAB1 during meiosis to
      mitosis transition. In contrast to maize, there are only 6 homologous genes in
      the model plant Arabidopsis, while this family has largely expanded in grasses.
      Here, we report a phylogenetic analysis of the MATH-BTB gene family in 9 land
      plant species including various mosses, eudicots, and grasses. We extend a
      previous classification of the plant MATH-BTB family and additionally arrange the
      expanded group into 5 grass-specific clades. Synteny studies indicate that
      expansion occurred to a large extent due to local gene duplications. Expression
      studies of 3 closely related MATH-BTB genes in maize (MAB1-3) indicate highly
      specific expression pattern. In summary, this work provides a solid base for
      further studies comparing genetic and functional information of the MATH-BTB
      family especially in the grasses. 

PMID- 25764422
TI  - Say it with flowers: Flowering acceleration by root communication.
AB  - The timing of reproduction is a critical determinant of fitness, especially in
      organisms inhabiting seasonal environments. Increasing evidence suggests that
      inter-plant communication plays important roles in plant functioning. Here, we
      tested the hypothesis that flowering coordination can involve communication
      between neighboring plants. We show that soil leachates from Brassica rapa plants
      growing under long-day conditions accelerated flowering and decreased allocation
      to vegetative organs in target plants growing under non-inductive short-day
      conditions. The results suggest that besides endogenous signaling and external
      abiotic cues, flowering timing may involve inter-plant communication, mediated by
      root exudates. The study of flowering communication is expected to illuminate
      neglected aspects of plant reproductive interactions and to provide novel
      opportunities for controlling the timing of plant reproduction in agricultural
      settings. 

PMID- 25764423
TI  - The plant stigma exudate. A biochemically active extracellular environment for
      pollen germination?
AB  - During sexual reproduction, pollen performance is greatly influenced by the
      female tissues. The stigma exudate, i.e., the extracellular secretion that covers
      the stigma outermost surface, has been usually regarded as a reservoir of water,
      secondary metabolites, cell wall precursors and compounds that serve as energy
      supply for rapid pollen tube growth. In an attempt to identify the proteins
      present in the stigma secretome, we performed a large-scale analysis in two
      species (Lilium longiflorum and Olea europaea) following a proteomic-based
      approach. The resulting data strongly suggest that the stigma exudate is not a
      mere storage site but also a biochemically active environment with a markedly
      catabolic nature. Thus, this secretion may modulate early pollen tube growth and
      contribute to the senescence of stigma after pollination. In addition, a putative
      cross-talk between genetic programs that regulate stress/defense and pollination
      responses in the stigma is also suggested. The stigma exudate might also
      functionally diverge between species on the basis on their ecology and the
      biochemical, morphological and anatomical features of their stigmas.
      Unexpectedly, we identified in both exudates some intracellular proteins,
      suggesting that a mechanism other than the canonical ER-Golgi exocytic pathway
      may exist in the stigma and contribute to exudate secretion. 

PMID- 25764424
TI  - The role of L-DOPA in plants.
AB  - Since higher plants regularly release organic compounds into the environment,
      their decay products are often added to the soil matrix and a few have been
      reported as agents of plant-plant interactions. These compounds, active against
      higher plants, typically suppress seed germination, cause injury to root growth
      and other meristems, and inhibit seedling growth. Mucuna pruriens is an example
      of a successful cover crop with several highly active secondary chemical agents
      that are produced by its seeds, leaves and roots. The main phytotoxic compound
      encountered is the non-protein amino acid L-3,4-dihydroxyphenylalanine (L-DOPA),
      which is used in treating the symptoms of Parkinson disease. In plants, L-DOPA is
      a precursor of many alkaloids, catecholamines, and melanin and is released from
      Mucuna into soils, inhibiting the growth of nearby plant species. This review
      summarizes knowledge regarding L-DOPA in plants, providing a brief overview about
      its metabolic actions. 

PMID- 25764425
TI  - Mechanisms of disruption of meristematic competence by microgravity in
      Arabidopsis seedlings.
AB  - Experiments performed in actively proliferating plant cells both in space and
      simulated microgravity have evidenced a common effect: cell proliferation appears
      enhanced whereas cell growth is depleted. Coordination of cell growth and
      proliferation, called meristematic competence, is a major feature of meristematic
      cells and its disruption may lead to important alterations in the developmental
      pattern of the plant. Auxin is known to be a mediator of the transduction of the
      gravitropic signal and a regulator of the rates of growth and proliferation in
      meristematic cells, as well as of their further differentiation. Therefore,
      gravity sensing, gravitropism, auxin levels, and meristematic competence are
      mutually interrelated. However, our experiments in simulated microgravity, using
      both mechanical and magnetic levitation technologies, have revealed that this
      interdependence is neither strict nor univocal and may include additional factors
      and mechanisms. Available data indicate that altered gravity may affect cell
      growth and proliferation by mechanisms alternative to the transduction of the
      gravitropic signal perceived by columella cells in the root tip. These mechanisms
      would include gravity sensing independent from statolith displacement and
      transduction mediators other than polar auxin transport. 

PMID- 25764426
TI  - Drought stress modulates oxylipin signature by eliciting 12-OPDA as a potent
      regulator of stomatal aperture.
AB  - Through evolution, plants have developed a myriad of strategies to adapt to
      environmental perturbations. Using 3 Arabidopsis ecotypes in conjunction with
      various transgenic and mutant lines, we provide evidence that wounding and
      drought differentially alter the metabolic signatures derived from the 2 main
      competing oxylipin-pathway branches, namely the JA and its precursor 12-OPDA
      produced by Allene oxide synthase (AOS) branch, and aldehydes and corresponding
      alcohols generated by Hydroperoxide lyase (HPL) branch. Specifically, we show
      that wounding induces production of both HPL and AOS-derived metabolites whereas,
      drought stress only elicits production of hexenal but suppresses hexenol, and
      further uncouples the conversion of 12-OPDA to JA. This finding led to uncovering
      of 12-OPDA as a functional convergence point of oxylipin and ABA pathways to
      control stomatal aperture in plant adaptive responses to drought. In addition,
      using transgenic lines overexpressing plastidial and extraplastidial HPL enzyme
      establish the strong interdependence of AOS- and HPL-branch pathways, and the
      importance of this linkage in tailoring plant adaptive responses to the nature of
      perturbations. 

PMID- 25764427
TI  - Toward deciphering the genome-wide transcriptional responses of rice to phosphate
      starvation and recovery.
AB  - Phosphate (Pi) limitation is one of the major factors negatively impacting crop
      yield worldwide. Next generation sequencing (NGS) was used to profile the
      transcriptomes of rice (Oryza sativa) roots and shoots after phosphate starvation
      and recovery, shedding further light on the complex and dynamic mechanisms
      involved in Pi homeostasis. The use of NGS also enabled the identification of
      previously not annotated loci and novel isoforms of genes that are specifically
      induced by Pi starvation. Furthermore, phosphate re-feeding was observed to have
      a unique response with a variety of transcription factors and kinases induced in
      a transient manner. Expression profiles of miRNAs were also assessed upon long
      term Pi starvation in roots and shoots revealing several novel miRNAs associated
      with Pi starvation. Altogether, this study provides key findings regarding Pi
      homeostasis in plants that will provide a valuable resource for research aimed at
      generating crops with increased Pi acquisition/use efficiency. 

PMID- 25764428
TI  - Heterotrimeric G-proteins in green algae. An early innovation in the evolution of
      the plant lineage.
AB  - Heterotrimeric G-proteins (G-proteins, hereafter) are important signaling
      components in all eukaryotes. The absence of these proteins in the sequenced
      genomes of Chlorophycean green algae has raised questions about their
      evolutionary origin and prevalence in the plant lineage. The existence of G
      proteins has often been correlated with the acquisition of embryophytic life
      cycle and/or terrestrial habitats of plants which occurred around 450 million
      years ago. Our discovery of functional G-proteins in Chara braunii, a
      representative of the Charophycean green algae, establishes the existence of this
      conserved signaling pathway in the most basal plants and dates it even further
      back to 1-1.5 billion years ago. We have now identified the sequence homologs of
      G-proteins in additional algal families and propose that green algae represent a
      model system for one of the most basal forms of G-protein signaling known to
      exist to date. Given the possible differences that exist between plant and
      metazoan G-protein signaling mechanisms, such basal organisms will serve as
      important resources to trace the evolutionary origin of proposed mechanistic
      differences between the systems as well as their plant-specific functions. 

PMID- 25764429
TI  - Vesicular trafficking in characean green algae and the possible involvement of a
      VAMP72-family protein.
AB  - The RAB5 GTPase ARA6 of Arabidopsis thaliana is known to be involved in endosomal
      trafficking by targeting vesicles to the plasma membrane. During this process
      AtARA6 is working in close relationship with the SNARE protein VAMP727 (vesicle
      associated membrane protein 727). Recently, ARA6 of the characean green algae
      Chara australis (CaARA6) was shown to have properties similar to AtARA6, pointing
      to similar trafficking pathways. In order to gain further insight into the
      vesicle trafficking machinery of Characeae, C. australis was analyzed for
      homologous proteins of the VAMP72-family. A CaVAMP72 protein was detected and
      classified by protein sequence alignment and phylogenetic analyses. 

PMID- 25764430
TI  - What lies ahead in post-genomics era.
AB  - Resistance breeding, especially for the lineage-exclusion (LEB) is essential to
      meet the caloric demand of ever-growing population as diseases, especially caused
      by fungal and fungus-like pathogens are posing a visible and imminent threat to
      sustainable world food supply. This article provides a fresh perspective on the
      application of genomics in the LEB. 

PMID- 25764431
TI  - Adventitious roots of wheat seedlings that emerge in oxygen-deficient conditions
      have increased root diameters with highly developed lysigenous aerenchyma.
AB  - Exposing roots of plants to hypoxic conditions is known to greatly improve their
      anoxic stress tolerance. We previously showed that pre-treatment of wheat
      seedlings with an ethylene precursor, 1-aminocyclopropanecarboxylic acid (ACC),
      enhanced their tolerance of oxygen-deficient conditions. Although ACC-pretreated
      seminal roots of wheat seedlings grown under oxygen-deficient conditions avoided
      root tip death, they elongated very little. In the present study, we assessed the
      effects of ethylene on the responses of adventitious roots of wheat seedlings to
      oxygen-deficient conditions. Lysigenous aerenchyma formation in the adventitious
      roots of wheat seedlings pretreated with ACC appeared to reduce tip death under
      oxygen-deficient conditions, but the adventitious roots, like the seminal roots,
      hardly elongated. We also found that adventitious roots that emerge in oxygen
      deficient conditions continued to elongate even under such conditions. The
      adventitious roots emerged in oxygen-deficient conditions were found to have
      thicker root diameters than those emerged in aerated conditions. These results
      suggest that the adventitious roots with thicker root diameters can better cope
      with oxygen-deficient conditions. Measurements of the area of the lysigenous
      aerenchyma confirmed that the increased root diameters have a greater amount of
      air space generated by lysigenous aerenchyma formation.

PMID- 25764432
TI  - Differential responses of Arabidopsis thaliana accessions to atmospheric nitrogen
      dioxide at ambient concentrations.
AB  - To better understand the response of plants to atmospheric nitrogen dioxide
      (NO2), we investigated biomass accumulation in 3 accessions of Arabidopsis
      thaliana: C24, Columbia (Col-0), and Landsberg erecta (Ler). Plants were grown in
      NO2-free air for 1 week after sowing, followed by 3 (Col-0 and Ler) to 4 (C24)
      weeks in air with or without NO2 (10 or 50 ppb). NO2 treatment increased the
      biomass of all 3 accessions to varying extents. Treatment with 10 ppb NO2
      increased shoot biomass in C24, Col-0, and Ler by 3.2-, 1.4-, and 2.3-fold,
      respectively, compared with control. Treatment with 50 ppb gave similar
      increases, except in C24 (2.7-fold). The physiological, evolutionary, and genetic
      significance of these results are discussed below. 

PMID- 25764433
TI  - Nanometer-scale elongation rate fluctuations in the Myriophyllum aquaticum
      (Parrot feather) stem were altered by radio-frequency electromagnetic radiation.
AB  - The emission of radio-frequency electromagnetic radiation (EMR) by various
      wireless communication base stations has increased in recent years. While there
      is wide concern about the effects of EMR on humans and animals, the influence of
      EMR on plants is not well understood. In this study, we investigated the effect
      of EMR on the growth dynamics of Myriophyllum aquaticum (Parrot feather) by
      measuring the nanometric elongation rate fluctuation (NERF) using a statistical
      interferometry technique. Plants were exposed to 2 GHz EMR at a maximum of 1.42
      Wm(-2) for 1 h. After continuous exposure to EMR, M. aquaticum plants exhibited a
      statistically significant 51 +/- 16% reduction in NERF standard deviation.
      Temperature observations revealed that EMR exposure did not cause dielectric
      heating of the plants. Therefore, the reduced NERF was due to a non-thermal
      effect caused by EMR exposure. The alteration in NERF continued for at least 2.5
      h after EMR exposure and no significant recovery was found in post-EMR NERF
      during the experimental period. 

PMID- 25764434
TI  - Auxin homeostasis, signaling, and interaction with other growth hormones during
      the clubroot disease of Brassicaceae.
AB  - The obligate biotrophic protist Plasmodiophora brassicae causes worldwide
      devastating losses on Brassica crops. Among these are oilseed rape, vegetable
      brassicas, and turnips. However, the fact that Arabidopsis thaliana is a good
      host for P. brassicae, has boosted research on the molecular interaction using
      the resources available for this model plant. Due to the uncontrolled growth of
      infected host root tissues the disease has been coined "clubroot." Consequently,
      during the last years, alterations in host hormone metabolisms have been
      described. Influencing the hormonal balance leads to aberrant growth responses in
      the clubbed roots. The discussion presented in the following will focus on growth
      promoting hormones, mainly auxins, with the interaction to other growth
      associated hormonal signaling pathways, such as cytokinins and brassinosteroids. 

PMID- 25764435
TI  - Galanthamine, an anti-cholinesterase drug, effects plant growth and development
      in Artemisia tridentata Nutt. via modulation of auxin and neurotransmitter
      signaling.
AB  - Galanthamine is a naturally occurring acetylcholinesterase (AchE) inhibitor that
      has been well established as a drug for treatment of mild to moderate Alzheimer
      disease, but the role of the compound in plant metabolism is not known. The
      current study was designed to investigate whether galanthamine could redirect
      morphogenesis of Artemisia tridentata Nutt. cultures by altering concentration of
      endogenous neurosignaling molecules acetylcholine (Ach), auxin (IAA), melatonin
      (Mel), and serotonin (5HT). Exposure of axenic A. tridentata cultures to 10 uM
      galanthamine decreased the concentration of endogenous Ach, IAA, MEL, and AchE,
      and altered plant growth in a manner reminiscent of 2-4D toxicity. Galanthamine
      itself demonstrated IAA activity in an oat coleoptile elongation bioassay, 20 uM
      galanthamine showed no significant difference compared with 5 MUM IAA or 5 MUM 1
      Naphthaleneacetic acid (NAA). Metabolomic analysis detected between 20,921 to
      27,891 compounds in A. tridentata plantlets and showed greater commonality
      between control and 5 uM treatments. Furthermore, metabolomic analysis putatively
      identified coumarins scopoletin/isoscopoletin, and scopolin in A. tridentata leaf
      extracts and these metabolites linearly increased in response to galanthamine
      treatments. Overall, these data indicate that galanthamine is an allelopathic
      phytochemical and support the hypothesis that neurologically active compounds in
      plants help ensure plant survival and adaptation to environmental challenges. 

PMID- 25764436
TI  - Expression of Arabidopsis TOL genes.
AB  - A strict control of abundance and localization of plasma membrane proteins is
      essential for plants to be able to respond quickly and accurately to a changing
      environment. The proteins responsible for the initial recognition and
      concentration of ubiquitinated plasma membrane proteins destined for degradation,
      are well characterized in mammals and yeast, (1) yet no clear orthologs were
      found in plants. (2) Recently, we have identified a family of proteins in higher
      plants, which function in vacuolar targeting and subsequent degradation of
      ubiquitinated plasma membrane proteins (3) (,) (4) termed TOM1-like (TOL)
      proteins. 

PMID- 25764437
TI  - Role of microRNA319 in creeping bentgrass salinity and drought stress response.
AB  - The microRNA319 family (miR319) is one of the most conserved and ancient microRNA
      (miRNA) families in plants. Transgenic creeping bentgrass (Agrostis stolonifera)
      overexpressing a rice miR319, Osa-miR319a, exhibited enhanced salt and drought
      tolerance. A comprehensive hypothetical model about the role of miR319 in
      creeping bentgrass response to salinity and drought stress was proposed. Salinity
      and drought stress induces elevated expression of miR319, resulting in
      downregulation of at least 4 putative target genes of miR319 (AsPCF5, AsPCF6,
      AsPCF8, and AsTCP14) as well as a homolog of the rice NAC domain gene AsNAC60,
      and therefore positively contributing to plant abiotic stress response. Hormones
      might also regulate miR319 and its targets, and the expression level of the
      miR319 targets might be a balance of miR319-mediated target cleavage and hormone
      regulation of the targets. Furthermore, HKT gene families involved in salt
      exclusion mechanisms as well as mechanisms controlling the timing of gene
      expression network are also hypothesized to play an important role in this
      pathway. 

PMID- 25764438
TI  - Fusarium mangiferae associated with mango malformation in the tarai region of the
      Uttarakhand state of India.
AB  - Mango malformation is the most dangerous disease to mango worldwide. There are
      hints that Fusarium mangiferae might be one of the probable casual agents of
      disease. Recently, we reported on Fusarium isolates obtained from the mango tarai
      region of Uttarakhand acquiring morphological features of F. mangiferae. Here,
      further confirmation of Fusarium isolates were made by PCR amplification using
      primers specific to the translation elongation factors 1alpha and beta-tubulin
      gene of F. mangiferae. Further, SDS-PAGE and RAPD profiles showed genetic
      variability among isolates of F. mangiferae. This study provides further direct
      evidence of involvement of different strains of F. mangiferae in malformation
      diseases of mango in the tarai region of the Uttarakhand state. 

PMID- 25764440
TI  - Successful treatment of Wilson disease-associated IgA pemphigus with IVIG.

PMID- 25764439
TI  - An appropriate concentration of arginine is required for normal root growth in
      rice.
AB  - Plant roots play an important role in uptake of water and nutrients, support of
      above-ground part and environmental sensing, but the molecular mechanisms
      underlying the root development are poorly understood in rice. We found that a
      gene (OsASL1) encoding argininosuccinate lyase is involved in normal root
      development of rice. OsASL1 cleaves argininosuccinate to arginine and fumarate
      reversibly, the last step in the arginine biosynthetic pathway. Here, we further
      characterized OsASL1 in terms of expression pattern, subcellular localization,
      and arginine effect on the root growth. A detailed expression analysis revealed
      that 2 transcripts of OsASL1, OsASL1.1 and OsASL1.2, showed different expression
      patterns; OsASL1.1 was expressed in most organs throughout the whole growth
      period, whereas OsASL1.2 was mainly expressed in the roots. In contrast to
      plastid-localized OsASL1.1, OsASL1.2 was localized to the cytosol and nucleus.
      The short-root phenotype of the mutant was not rescued by exogenous addition of
      the sodium nitroprusside, a nitric oxide donor, but rescued by an appropriate
      concentration of Arg. Our results indicate that the subcellular localization was
      determined by the N terminus of OsASL1 and that appropriate concentration of Arg
      is required for normal root elongation in rice. 

PMID- 25764441
TI  - Students' perceptions of peer-organized extra-curricular research course during
      medical school: a qualitative study.
AB  - Early integration of research education into medical curricula is crucial for
      evidence-based practice. Yet, many medical students are graduating with no
      research experience due to the lack of such integration in their medical school
      programs. The purpose of this study was to explore the impact of a peer
      organized, extra-curricular research methodology course on the attitudes of
      medical students towards research and future academic careers. Twenty one medical
      students who participated in a peer-organized research course were enrolled in
      three focus group discussions to explore their experiences, perceptions and
      attitudes towards research after the course. Discussions were conducted using a
      semi-structured interview guide, and were transcribed and thematically analyzed
      for major and minor themes identification. Our findings indicate that students'
      perceptions of research changed after the course from being difficult initially
      to becoming possible. Participants felt that their research skills and critical
      thinking were enhanced and that they would develop research proposals and
      abstracts successfully. Students praised the peer-assisted teaching approach as
      being successful in enhancing the learning environment and filling the curricular
      gap. In conclusion, peer-organized extra-curricular research courses may be a
      useful option to promote research interest and skills of medical students when
      gaps in research education in medical curricula exist. 

PMID- 25764442
TI  - Contrast-enhanced ultrasonography in differential diagnosis of benign and
      malignant ovarian tumors.
AB  - OBJECTIVE: To evaluate the accuracy of contrast-enhanced ultrasonography (CEUS)
      in differential diagnosis of benign and malignant ovarian tumors. METHODS: The
      scientific literature databases PubMed, Cochrane Library and CNKI were
      comprehensively searched for studies relevant to the use of CEUS technique for
      differential diagnosis of benign and malignant ovarian cancer. Pooled summary
      statistics for specificity (Spe), sensitivity (Sen), positive and negative
      likelihood ratios (LR+/LR-), and diagnostic odds ratio (DOR) and their 95%CIs
      were calculated. Software for statistical analysis included STATA version 12.0
      (Stata Corp, College Station, TX, USA) and Meta-Disc version 1.4 (Universidad
      Complutense, Madrid, Spain). RESULTS: Following a stringent selection process,
      seven high quality clinical trials were found suitable for inclusion in the
      present meta-analysis. The 7 studies contained a combined total of 375 ovarian
      cancer patients (198 malignant and 177 benign). Statistical analysis revealed
      that CEUS was associated with the following performance measures in differential
      diagnosis of ovarian tumors: pooled Sen was 0.96 (95%CI = 0.92~0.98); the summary
      Spe was 0.91 (95%CI = 0.86~0.94); the pooled LR+ was 10.63 (95%CI = 6.59~17.17);
      the pooled LR- was 0.04 (95%CI = 0.02~0.09); and the pooled DOR was 241.04 (95%
      CI = 92.61~627.37). The area under the SROC curve was 0.98 (95% CI = 0.20~1.00).
      Lastly, publication bias was not detected (t = -0.52, P = 0.626) in the meta
      analysis. CONCLUSIONS: Our results revealed the high clinical value of CEUS in
      differential diagnosis of benign and malignant ovarian tumors. Further, CEUS may
      also prove to be useful in differential diagnosis at early stages of this
      disease.

PMID- 25764443
TI  - Silver decahedral nanoparticles-enhanced fluorescence resonance energy transfer
      sensor for specific cell imaging.
AB  - We report on a silver decahedral nanoparticles (Ag10NPs)-based FRET (fluorescence
      resonance energy transfer) sensor for target cell imaging. Fluorophores
      functionalized aptamers (Sgc8-FITC) were bound with Ag10NPs via the SH group on
      the aptamer to form Ag10-Sgc8-FITC. Then, quencher-carrying strands (BHQ-1) were
      hybridized with Sgc8-FITC to form a Ag10NPs-based FRET sensor (Ag10-Sgc8-F/Q).
      The sensor interacted with membrane protein tyrosine kinase-7 (PTK-7) on the CCRF
      CEM (CCL-119, T-cell line, human acute lymphoblastic leukemia) cell surface to
      attain fluorescence imaging of CCRF-CEM cells. The addition of CCRF-CEM cells
      resulted in many sensors binding with cells membrane and the displacement of BHQ
      1, thus disrupting the FRET effect and the enhanced fluorescence intensity of
      FITC. It was found that Ag10NPs largely enhanced the fluorescence intensity of
      FITC. The results also showed that the Ag10NPs-based FRET sensor (Ag10-Sgc8-F/Q)
      was not only superior to the bare FRET sensor (Sgc8-F/Q) and sensor Ag-Sgc8-F/Q
      but also highly sensitive and specific for CCRF-CEM cells imaging. 

PMID- 25764444
TI  - Salmonella and Campylobacter contamination of ready-to-eat street-vended pork
      meat dishes in Antananarivo, Madagascar: a risk for the consumers?
AB  - Street-food vending has been increasing in many developing countries and
      particularly in Madagascar since 2000. Gastroenteric diseases cause 37% of all
      deaths each year, and 50% of children <5 years are infected with intestinal
      pathogens. However, there has been little information regarding the incidence of
      street-food-related diseases, or foodborne pathogens in pork, which is the most
      commonly eaten meat, along with chicken. Thus, the aim of this study was to
      investigate the safety of traditional ready-to-eat street-vended pork dishes and
      to assess the association of restaurant characteristics and cooking practices
      with Salmonella and Campylobacter contamination of these meals. Sixty street
      restaurants were studied from March 2012 to August 2012 in Antananarivo. A
      questionnaire was submitted to the managers, and samples of ready-to-eat pork
      dishes were bought. Salmonella spp. were isolated in 10% of the 60 street
      restaurants studied and in 5% samples of pork dishes. The most prevalent serovars
      isolated were Salmonella Typhimurium (44%) and Senftenberg (33%). Campylobacter
      was not detected. Only 4 of the 43 variables tested in the screening analysis
      were significantly associated with Salmonella spp. contamination of the street
      restaurants. The risk for a restaurant to be Salmonella positive decreased when
      there were specific premises for the restaurant and when the staff was wearing
      specific clothes when working. Conversely, that risk increased when the
      temperature of ready-to-eat pork was <52  degrees C and when tablecloths were
      used in the restaurant.

PMID- 25764445
TI  - Three gastroenteritis outbreaks in South Korea caused by the consumption of
      kimchi tainted by norovirus GI.4.
AB  - BACKGROUND: In April 2013, outbreaks of acute gastroenteritis were reported at
      three schools in Jeonju, South Korea. Epidemiological investigations were
      performed to characterize the outbreaks and implement appropriate control
      measures. MATERIALS AND METHODS: Retrospective cohort studies were performed at
      these schools. Stool and environmental samples were collected for bacterial and
      viral assessment. A food supplier of the schools, food company X, was inspected,
      and samples of cabbage kimchi and groundwater were tested for norovirus by real
      time reverse-transcriptase polymerase chain reaction. The relatedness of the
      detected norovirus strains was evaluated by phylogenetic analysis. RESULTS: Of
      the 3347 questionnaires distributed, 631 (attack rate: 18.9%) met the case
      definition. Among the consumed food items, kimchi products (i.e., cabbage and
      fresh kimchi) were significantly associated with illness. The kimchi products
      were supplied by food company X. Among stool samples from 95 students and 34 food
      handlers at the 3 schools, 39 (41.1%) and 14 (41.2%) samples, respectively, were
      positive for norovirus. The samples of groundwater and cabbage kimchi at food
      company X were positive for norovirus. The predominant genotype of norovirus
      detected in the patient, groundwater, and cabbage kimchi samples, GI.4, shared
      high nucleotide identity. CONCLUSIONS: Kimchi products tainted with norovirus
      GI.4 from contaminated groundwater were linked to the acute gastroenteritis
      outbreaks. Therefore, kimchi manufacturers in South Korea should apply chlorine
      disinfection when using groundwater. Moreover, more stringent sanitation
      requirements and strict regulations for food companies are recommended.

PMID- 25764446
TI  - The biomarker paradigm: between diagnostic efficiency and clinical efficacy.
AB  - The interest in biomarker research has been growing exponentially, and this trend
      is not expected to reverse soon. Although the clinical usefulness of laboratory
      tests is conventionally defined in terms of diagnostic efficiency or clinical
      efficacy (or effectiveness), these notions are complementary but not
      interchangeable. The former concept is an expression of diagnostic accuracy but
      does not entail outcome assessment. Conversely, clinical efficacy investigates
      whether or not a certain test can produce significant changes in managed care and
      an improvement of clinical outcomes. The vast majority of published studies were
      mainly focused on diagnostic efficacy rather than on clinical efficacy, and this
      seems no longer sustainable in a world with limited resources. Although bridging
      the gap between efficiency and efficacy is not a trivial endeavour, a paradigm
      shift is necessary, wherein the laboratory community should focus on what
      clinicians need rather than pursuing an endless search for analytically perfect
      tests. In the foreseeable future, efficacy should be improved by translating this
      concept into a simple "six R" paradigm, namely, performing the Right test, with
      the Right method, at the Right time, to the Right patient, at the Right cost, for
      the Right outcome. 

PMID- 25764447
TI  - Tolerability and pharmacokinetic profile of a novel benzene-poly-carboxylic acids
      complex with cis-diammineplatinum (II) dichloride in dogs with malignant mammary
      tumours.
AB  - The pharmacokinetic profile, tolerability and efficacy of benzene-poly-carboxylic
      acids complex with cis-diammineplatinum (II) dichloride (BP-C1) were studied in
      dogs with mammary cancer. A three-level response surface pathway designed trial
      was performed on seven dogs. At each level BP-C1 was administered subcutaneously
      daily for 7 days followed by a 7-day rest period in a dose escalating manner.
      Adverse events according to VCOG-CTCAE, performance status and tumour progression
      were recorded. The pharmacokinetic profile followed a two-compartment model with
      rapid absorption, short distribution, and a slow elimination phase. The overall
      elimination half-life was 125 h. The maximum tolerated dose of BP-C1 was
      estimated to be above 0.46 mg kg-1 . A significant reduction in VCOG-CTCAE
      toxicity which correlated negatively with increasing dose was found. The dogs'
      general performance status remained unchanged. No decrease in total tumour burden
      was found, although temporary tumour reduction was seen in some target tumours.

PMID- 25764448
TI  - Effect of low-level laser therapy on mesenchymal stem cell proliferation: a
      systematic review.
AB  - Low-level laser therapy (LLLT) has been used in several in vitro experiments in
      order to stimulate cell proliferation. Cells such as fibroblasts, keratinocytes,
      lymphocytes, and osteoblasts have shown increased proliferation when submitted to
      laser irradiation, although little is known about the effects of LLLT on stem
      cells. This study aims to assess, through a systematic literature review, the
      effects of LLLT on the in vitro proliferation of mesenchymal stem cells. Using
      six different terms, we conducted an electronic search in PubMed/Medline database
      for articles published in the last twelve years. From 463 references obtained,
      only 19 papers met the search criteria and were included in this review. The
      analysis of the papers showed a concentration of experiments using LLLT on stem
      cells derived from bone marrow, dental pulp, periodontal ligament, and adipose
      tissue. Several protocols were used to irradiate the cells, with variations on
      wavelength, power density, radiation time, and state of light polarization. Most
      studies demonstrated an increase in the proliferation rate of the irradiated
      cells. It can be concluded that the laser therapy positively influences the in
      vitro proliferation of stem cells studied, being necessary to carry out further
      experiments on other cell types and to uniform the methodological designs. 

PMID- 25764449
TI  - Photodynamic antimicrobial effects of bis-indole alkaloid indigo from Indigofera
      truxillensis Kunth (Leguminosae).
AB  - Multidrug-resistant microbial infections represent an exponentially growing
      problem affecting communities worldwide. Photodynamic therapy is a promising
      treatment based on the combination of light, oxygen, and a photosensitizer that
      leads to reactive oxygen species production, such as superoxide (type I
      mechanism) and singlet oxygen (type II mechanism) that cause massive oxidative
      damage and consequently the host cell death. Indigofera genus has gained
      considerable interest due its mutagenic, cytotoxic, and genotoxic activity.
      Therefore, this study was undertaken to investigate the effect of crude extracts,
      alkaloidal fraction, and isolated substance derived from Indigofera truxillensis
      in photodynamic antimicrobial chemotherapy on the viability of bacteria and yeast
      and evaluation of mechanisms involved. Our results showed that all samples
      resulted in microbial photoactivation in subinhibitory concentration, with indigo
      alkaloid presenting a predominant photodynamic action through type I mechanism.
      The use of CaCl2 and MgCl2 as cell permeabilizing additives also increased gram
      negative bacteria susceptibility to indigo.

PMID- 25764450
TI  - Evaluating vaccine avoidance from a wider angle.

PMID- 25764452
TI  - Adverse events of anti-tumor necrosis factor alpha therapy in ankylosing
      spondylitis.
AB  - OBJECTIVE: This study aims to investigate the prevalence of short-term and long
      term adverse events associated with tumor necrosis factor-alpha (TNF-alpha)
      blocker treatment in Chinese Han patients suffering from ankylosing spondylitis
      (AS). METHODS: The study included 402 Chinese Han AS patients treated with TNF
      alpha blockers. Baseline data was collected. All patients were monitored for
      adverse events 2 hours following administration. Long-term treatment was
      evaluated at 8, 12, 52 and 104 weeks follow-up for 172 patients treated with TNF
      alpha blockers. RESULTS: Short-term adverse events occurred in 20.15% (81/402),
      including rash (3.5%; 14/402), pruritus (1.2%; 5/402), nausea (2.2%; 9/402),
      headache (0.7%; 3/402), skin allergies (4.0%; 16/402), fever (0.5%; 2/402),
      palpitations (3.0%; 12/402), dyspnea (0.5%; 2/402), chest pain (0.2%; 1/402),
      [corrected] abdominal pain (1.0%; 4/402), hypertension (2.2%; 9/402), papilledema
      (0.5%; 2/402), laryngeal edema (0.2%; 1/402) and premature ventricular
      contraction (0.2%; 1/402). Long-term adverse events occurred in 59 (34.3%;
      59/172) patients, including pneumonia (7.6%; 13/172), urinary tract infections
      (9.9%; 17/172), otitis media (4.7%; 8/172), tuberculosis are (3.5%; 6/172)
      [corrected], abscess (1.2%; 2/172), oral candidiasis (0.6%; 1/172), elevation of
      transaminase (1.7%; 3/172), anemia (1.2%; 2/172), hematuresis (0.6%; 1/172),
      constipation (2.3%; 4/172), weight loss (0.6%; 1/172), exfoliative dermatitis
      (0.6%; 1/172). CRP, ESR and disease duration were found to be associated with an
      increased risk of immediate and long-term adverse events (P<0.05). Long-term
      treatment with Infliximab was associated with more adverse events than rhTNFR-Fc
      (P<0.01). CONCLUSION: This study reports on the prevalence of adverse events in
      short-term and long-term treatment with TNF-alpha blocker monotherapy in Chinese
      Han AS patients. Duration of disease, erythrocyte sedimentation rate, and c
      reactive protein serum levels were found to be associated with increased adverse
      events with anti-TNF-alpha therapy. Long-term treatment with Infliximab was
      associated with more adverse events than rhTNFR-Fc.

PMID- 25764453
TI  - Biosynthesis of Resveratrol in Blastospore of the Macrofungus Tremella
      fuciformis.
AB  - Tremella fuciformis is a known edible macrofungus that has medicinal value. It is
      widely cultivated in China and its products are distributed worldwide. In this
      study, a novel bioconversion system was established to produce resveratrol in the
      blastospore of T. fuciformis (bTf). The expression vector ptro1-4cl-rs that
      contains 4-coumarate:coenzyme A ligase gene (4cl) and resveratrol synthase gene
      (rs) was transformed into bTf by LiAc/PEG-mediated transformation. PCR and
      southern blotting analysis verified the successful integration of the exogenous
      4cl and rs genes into the genome of bTf. HPLC analysis confirmed that two
      transformants can convert p-coumaric acid into resveratrol (0.92 and 0.83 MUg/g
      resveratrol of dry weight within 7 days). This study is the first to report about
      the transformation and expression of resveratrol biosynthetic genes in bTf. This
      research is a significant step toward obtaining resveratrol-producing T.
      fuciformis strains, which not only satisfy the demand of resveratrol market, but
      also expand the category of functional food.

PMID- 25764454
TI  - Development of a VHH-Based Erythropoietin Quantification Assay.
AB  - Erythropoietin (EPO) quantification during cell line selection and bioreactor
      cultivation has traditionally been performed with ELISA or HPLC. As these
      techniques suffer from several drawbacks, we developed a novel EPO quantification
      assay. A camelid single-domain antibody fragment directed against human EPO was
      evaluated as a capturing antibody in a label-free biolayer interferometry-based
      quantification assay. Human recombinant EPO can be specifically detected in
      Chinese hamster ovary cell supernatants in a sensitive and pH-dependent manner.
      This method enables rapid and robust quantification of EPO in a high-throughput
      setting. 

PMID- 25764455
TI  - Cytoplasmic localization and asymmetric division in the early embryo of
      Caenorhabditis elegans.
AB  - During the initial cleavages of the Caenorhabditis elegans embryo, a series of
      rapid and invariant asymmetric cell divisions pattern the fate, size, and
      position of four somatic blastomeres and a single germline blastomere. These
      asymmetric divisions are orchestrated by a collection of maternally deposited
      factors that are initially symmetrically distributed in the newly fertilized
      embryo. Maturation of the sperm-derived centrosome in the posterior cytoplasm
      breaks this symmetry by triggering a dramatic and highly stereotyped partitioning
      of these maternal factors. A network of conserved cell polarity regulators, the
      PAR proteins, form distinct anterior and posterior domains at the cell cortex.
      From these domains, the PAR proteins direct the segregation of somatic and
      germline factors into opposing regions of the cytoplasm such that, upon cell
      division, they are preferentially inherited by the somatic blastomere or the
      germline blastomere, respectively. The segregation of these factors is
      controlled, at least in part, by a series of reaction-diffusion mechanisms that
      are asymmetrically deployed along the anterior/posterior axis. The
      characterization of these mechanisms has important implications for our
      understanding of how cells are polarized and how spatial organization is
      generated in the cytoplasm. For further resources related to this article, please
      visit the WIREs website.

PMID- 25764458
TI  - High diversity of protistan plankton communities in remote high mountain lakes in
      the European Alps and the Himalayan mountains.
AB  - We analyzed the genetic diversity (V4 region of the 18S rRNA) of planktonic
      microbial eukaryotes in four high mountain lakes including two remote
      biogeographic regions (the Himalayan mountains and the European Alps) and
      distinct habitat types (clear and glacier-fed turbid lakes). The recorded high
      genetic diversity in these lakes was far beyond of what is described from high
      mountain lake plankton. In total, we detected representatives from 66 families
      with the main taxon groups being Alveolata (55.0% OTUs 97%, operational taxonomic
      units), Stramenopiles (34.0% OTUs 97%), Cryptophyta (4.0% OTUs 97%),
      Chloroplastida (3.6% OTUs 97%) and Fungi (1.7% OTUs 97%). Centrohelida,
      Choanomonada, Rhizaria, Katablepharidae and Telonema were represented by <1% OTUs
      97%. Himalayan lakes harbored a higher plankton diversity compared to the Alpine
      lakes (Shannon index). Community structures were significantly different between
      lake types and biogeographic regions (Fisher exact test, P < 0.01). Network
      analysis revealed that more families of the Chloroplastida (10 vs 5) and the
      Stramenopiles (14 vs 8) were found in the Himalayan lakes than in the Alpine
      lakes and none of the fungal families was shared between them. Biogeographic
      aspects as well as ecological factors such as water turbidity may structure the
      microbial eukaryote plankton communities in such remote lakes.

PMID- 25764459
TI  - Metagenomic analysis reveals adaptations to a cold-adapted lifestyle in a low
      temperature acid mine drainage stream.
AB  - An acid mine drainage (pH 2.5-2.7) stream biofilm situated 250 m below ground in
      the low-temperature (6-10 degrees C) Kristineberg mine, northern Sweden,
      contained a microbial community equipped for growth at low temperature and acidic
      pH. Metagenomic sequencing of the biofilm and planktonic fractions identified the
      most abundant microorganism to be similar to the psychrotolerant acidophile,
      Acidithiobacillus ferrivorans. In addition, metagenome contigs were most similar
      to other Acidithiobacillus species, an Acidobacteria-like species, and a
      Gallionellaceae-like species. Analyses of the metagenomes indicated functional
      characteristics previously characterized as related to growth at low temperature
      including cold-shock proteins, several pathways for the production of compatible
      solutes and an anti-freeze protein. In addition, genes were predicted to encode
      functions related to pH homeostasis and metal resistance related to growth in the
      acidic metal-containing mine water. Metagenome analyses identified microorganisms
      capable of nitrogen fixation and exhibiting a primarily autotrophic lifestyle
      driven by the oxidation of the ferrous iron and inorganic sulfur compounds
      contained in the sulfidic mine waters. The study identified a low diversity of
      abundant microorganisms adapted to a low-temperature acidic environment as well
      as identifying some of the strategies the microorganisms employ to grow in this
      extreme environment. 

PMID- 25764457
TI  - Polyphenol-rich sorghum brans alter colon microbiota and impact species diversity
      and species richness after multiple bouts of dextran sodium sulfate-induced
      colitis.
AB  - The microbiota affects host health, and dysbiosis is involved in colitis. Sorghum
      bran influences butyrate concentrations during dextran sodium sulfate (DSS)
      colitis, suggesting microbiota changes. We aimed to characterize the microbiota
      during colitis, and ascertain if polyphenol-rich sorghum bran diets mitigate
      these effects. Rats (n = 80) were fed diets containing 6% fiber from cellulose,
      or Black (3-deoxyanthocyanins), Sumac (condensed tannins), or Hi Tannin black
      (both) sorghum bran. Inflammation was induced three times using 3% DSS for 48 h
      (40 rats, 2 week separation), and the microbiota characterized by pyrosequencing.
      The Firmicutes/Bacteroidetes ratio was higher in Cellulose DSS rats. Colonic
      injury negatively correlated with Firmicutes, Actinobacteria, Lactobacillales and
      Lactobacillus, and positively correlated with Unknown/Unclassified. Post DSS#2,
      richness was significantly lower in Sumac and Hi Tannin black. Post DSS#3
      Bacteroidales, Bacteroides, Clostridiales, Lactobacillales and Lactobacillus were
      reduced, with no Clostridium identified. Diet significantly affected
      Bacteroidales, Bacteroides, Clostridiales and Lactobacillus post DSS#2 and #3.
      Post DSS#3 diet significantly affected all genus, including Bacteroides and
      Lactobacillus, and diversity and richness increased. Sumac and Hi Tannin black
      DSS had significantly higher richness compared to controls. Thus, these sorghum
      brans may protect against alterations observed during colitis including reduced
      microbial diversity and richness, and dysbiosis of Firmicutes/Bacteroidetes. 

PMID- 25764460
TI  - Diverse ecological roles within fungal communities in decomposing logs of Picea
      abies.
AB  - Fungal communities in Norway spruce (Picea abies) logs in two forests in Sweden
      were investigated by 454-sequence analyses and by examining the ecological roles
      of the detected taxa. We also investigated the relationship between fruit bodies
      and mycelia in wood and whether community assembly was affected by how the dead
      wood was formed. Fungal communities were highly variable in terms of phylogenetic
      composition and ecological roles: 1910 fungal operational taxonomic units (OTUs)
      were detected; 21% were identified to species level. In total, 58% of the OTUs
      were ascomycetes and 31% basidiomycetes. Of the 231 337 reads, 38% were
      ascomycetes and 60% basidiomycetes. Ecological roles were assigned to 35% of the
      OTUs, accounting for 62% of the reads. Wood-decaying fungi were the most common
      group; however, other saprotrophic, mycorrhizal, lichenized, parasitic and
      endophytic fungi were also common. Fungal communities in logs formed by stem
      breakage were different to those in logs originating from butt breakage or
      uprooting. DNA of specific species was detected in logs many years after the last
      recorded fungal fruiting. Combining taxonomic identification with knowledge of
      ecological roles may provide valuable insights into properties of fungal
      communities; however, precise ecological information about many fungal species is
      still lacking. 

PMID- 25764461
TI  - Variability in responses of bacterial communities and nitrogen oxide emission to
      urea fertilization among various flooded paddy soils.
AB  - Fertilization affects bacterial communities and element biogeochemical cycling in
      flooded paddy soils and the effect might differ among soil types. In this study,
      five paddy soils from Southern China were subjected to urea addition to explore
      impacts of fertilization on nitrogen oxide (N2O) emission and bacterial community
      composition under the flooding condition. 16S rRNA gene-based illumina sequencing
      showed no obvious shifts in bacterial community composition of five soils after
      urea addition. However, some genera were affected by fertilization addition and
      the influenced genera varied among soils. During the late period (day 8-19) of
      flooding incubation without urea addition, N2O emission rates were elevated for
      all soils. However, urea effects on N2O emission were different among flooded
      soils. For soils where nirS and nirK gene abundances increased with urea
      addition, N2O emission was significantly increased compared to control treatment.
      Redundancy analysis showed that dissolved organic carbon, ammonium (NH4 (+)),
      ferrous iron (Fe(2+)) and nitrate (NO3 (-)) in pore water explained 33.4% of the
      variation in soil bacterial community composition, implying that urea regimes
      influenced the relative abundance of some bacterial populations possibly by
      regulating soil characteristics and then influencing N2O emission. These results
      provided insights into soil type-dependent effect of fertilization on the overall
      bacterial communities and nitrogen oxide emission in flooded paddy soils. 

PMID- 25764462
TI  - Ammonia-limited conditions cause of Thaumarchaeal dominance in volcanic grassland
      soil.
AB  - The first step of nitrification is carried out by ammonia-oxidizing bacteria
      (AOB) and archaea (AOA). It is largely unknown, by which mechanisms these
      microbes are capable of coexistence and how their respective contribution to
      ammonia oxidation may differ with varying soil characteristics. To determine how
      different levels of ammonium availability influence the extent of archaeal and
      bacterial contributions to ammonia oxidation, microcosm incubations with
      controlled ammonium levels were conducted. Net nitrification was monitored and
      ammonia-oxidizer communities were quantified. Additionally, the nitrification
      inhibitor allylthiourea (ATU) was applied to discriminate between archaeal and
      bacterial contributions to soil ammonia oxidation. Thaumarchaeota, which were the
      only ammonia oxidizers detectable at the start of the incubation, grew in all
      microcosms, but AOB later became detectable in ammonium amended microcosms. Low
      and high additions of ammonium increasingly stimulated AOB growth, while AOA were
      only stimulated by the low addition. Treatment with ATU had no effect on net
      nitrification and sizes of ammonia-oxidizing communities suggesting that the
      effective concentration of ATU to discriminate between archaeal and bacterial
      ammonia oxidation is not the same in different soils. Our results support the
      niche-differentiating potential of ammonium concentration for AOA and AOB, and we
      conclude that ammonium limitation can be a major reason for absence of detectable
      AOB in soil. 

PMID- 25764463
TI  - Genetic characterization of fluoroquinolone resistant Escherichia coli from urban
      streams and municipal and hospital effluents.
AB  - Escherichia coli with reduced susceptibility to ciprofloxacin, isolated from
      urban streams, wastewater treatment plants and hospital effluent between 2004 and
      2012, were compared based on multilocus sequence typing (MLST), quinolone and
      beta-lactam resistance determinants and plasmid replicon type. Isolates from the
      different types of water and isolation dates clustered together, suggesting the
      persistence and capacity to propagate across distinct aquatic environments. The
      most prevalent MLST groups were ST10 complex and ST131. Almost all isolates (98%)
      carried mutations in the chromosomal genes gyrA and/or parC, and 10% possessed
      the genes qepA, aac(6('))-Ib-cr and/or qnrS1. Over 80% of the isolates were
      resistant to three or more classes of antibiotics (MDR >= 3). The most prevalent
      beta-lactamase encoding gene was blaTEM, followed by blaCTX-M-15, co-existing
      with plasmid mediated quinolone resistance. The plasmid replicon types of the
      group IncF were the most prevalent and distributed by different MLST groups. The
      genes aac(6('))-Ib-cr and/or qnrS1 could be transferred by conjugation in
      combination with the genes blaTEM,blaSHV-12 or blaOXA-1 and the plasmid replicon
      types I1-Igamma, K, HI2 and/or B/O. The potential of multidrug resistant E. coli
      with reduced susceptibility to ciprofloxacin, harboring mobile genetic elements
      and with ability to conjugate and transfer resistance genes, to spread and
      persist across different aquatic environments was demonstrated. 

PMID- 25764456
TI  - Census of bacterial microbiota associated with the glacier ice worm
      Mesenchytraeus solifugus.
AB  - The glacier ice worm, Mesenchytraeus solifugus, is a unique annelid, inhabiting
      only snow and ice in North American glaciers. Here, we analyzed the taxonomic
      composition of bacteria associated with M. solifugus based on the 16S rRNA gene.
      We analyzed four fixed-on-site and 10 starved ice worm individuals, along with
      glacier surface samples. In total, 1341 clones of 16S rRNA genes were analyzed
      for the ice worm samples, from which 65 bacterial phylotypes (99.0% cut-off) were
      identified. Of these, 35 phylotypes were closely related to sequences obtained
      from their habitat glacier and/or other components of cryosphere; whereas three
      dominant phylotypes were affiliated with animal-associated lineages of the class
      Mollicutes. Among the three, phylotype Ms-13 shared less than 89% similarity with
      database sequences and was closest to a gut symbiont of a terrestrial earthworm.
      Using fluorescence in situ hybridization, Ms-13 was located on the gut wall
      surface of the ice worms. We propose a novel genus and species, 'Candidatus
      Vermiplasma glacialis', for this bacterium. Our results raise the possibility
      that the ice worm has exploited indigenous glacier bacteria, while several
      symbiotic bacterial lineages have maintained their association with the ice worm
      during the course of adaptive evolution to the permanently cold environment. 

PMID- 25764464
TI  - Methanogenesis at extremely haloalkaline conditions in the soda lakes of Kulunda
      Steppe (Altai, Russia).
AB  - Microbial methanogenesis at extreme conditions of saline alkaline soda lakes has,
      so far, been poorly investigated. Despite the obvious domination of
      sulfidogenesis as the therminal anaerobic process in the hypersaline soda lakes
      of Kulunda Steppe (Altai, southwestern Siberia), high concentrations of methane
      were detected in the anaerobic sediments. Potential activity measurements with
      different substrates gave results significantly deviating from what is commonly
      found in hypersaline habitats with neutral pH. In particular, not only a non
      competitive methylotrophic pathway was active, but also lithotrophic and, in some
      cases, even acetate-dependent methanogenesis was found to be present in
      hypersaline soda lake sediments. All three pathways were functioning exclusively
      within the alkaline pH range between 8 and 10.5, while the salt concentration was
      the key factor influencing the activity. Methylotrophic and, to a lesser extent,
      lithotrophic methanogenesis were active up to soda-saturating conditions (4 M
      total Na(+)). Acetate-dependent methanogenesis was observed at salinities below 3
      M total Na(+). Detection of methanogens in sediments using the mcrA gene as a
      functional marker demonstrated domination of methylotrophic genera Methanolobus
      and Methanosalsum and lithotrophic Methanocalculus. In a few cases, acetoclastic
      Methanosaeta was detected, as well as two deep lineage methanogens. Cultivation
      results corresponded well to the mcrA-based observations. Enrichments for
      natronophilic methylotrophic methanogens resulted in isolation of Methanolobus
      strains at moderate salinity, while at salt concentrations above 2 M Na(+) a
      novel member of the genus Methanosalsum was dominating. Enrichments with H2 or
      formate invariably resulted in domination of close relatives of Methanocalculus
      natronophilus. Enrichments with acetate at low salt concentration yielded two
      acetoclastic alkaliphilic Methanosaeta cultures, while at salinity above 1 M
      Na(+) syntrophic associations were apparently responsible for the observed
      acetate conversion to methane. Overall, the results indicated the presence of
      functionally structured and active methanogenic populations in Siberian
      hypersaline soda lakes. 

PMID- 25764465
TI  - Biotic and abiotic effects on CO2 sequestration during microbially-induced
      calcium carbonate precipitation.
AB  - In this study, CO2 sequestration was investigated through the microbially-induced
      calcium carbonate precipitation (MICP) process with isolates obtained from a cave
      called 'Cave Without A Name' (Boerne, TX, USA) and the Pamukkale travertines
      (Denizli, Turkey). The majority of the bacterial isolates obtained from these
      habitats belonged to the genera Sporosarcina, Brevundimonas, Sphingobacterium and
      Acinetobacter. The isolates were investigated for their capability to precipitate
      calcium carbonate and sequester CO2. Biotic and abiotic effects of CO2
      sequestration during MICP were also investigated. In the biotic effect, we
      observed that the rate and concentration of CO2 sequestered was dependent on the
      species or strains. The main abiotic factors affecting CO2 sequestration during
      MICP were the pH and medium components. The increase in pH led to enhanced CO2
      sequestration by the growth medium. The growth medium components, on the other
      hand, were shown to affect both the urease activity and CO2 sequestration.
      Through the Plackett-Burman experimental design, the most important growth medium
      component involved in CO2 sequestration was determined to be urea. The optimized
      medium composition by the Plackett-Burman design for each isolate led to a
      statistically significant increase, of up to 148.9%, in CO2 uptake through
      calcification mechanisms. 

PMID- 25764466
TI  - Ecology and biotechnological potential of the thermophilic fermentative
      Coprothermobacter spp.
AB  - Thermophilic bacteria have been isolated from several terrestrial, marine and
      industrial environments. Anaerobic digesters treating organic wastes are often an
      important source of these microorganisms, which catalyze a wide array of
      metabolic processes. Moreover, organic wastes are primarily composed of proteins,
      whose degradation is often incomplete. Coprothermobacter spp. are proteolytic
      anaerobic thermophilic microbes identified in several studies focused on the
      analysis of the microbial community structure in anaerobic thermophilic reactors.
      They are currently classified in the phylum Firmicutes; nevertheless, several
      authors showed that the Coprothermobacter group is most closely related to the
      phyla Dictyoglomi and Thermotoga. Since only a few proteolytic anaerobic
      thermophiles have been characterized so far, this microorganism has attracted the
      attention of researchers for its potential applications with high-temperature
      environments. In addition to proteolysis, Coprothermobacter spp. showed several
      metabolic abilities and may have a biotechnological application either as source
      of thermostable enzymes or as inoculum in anaerobic processes. Moreover, they can
      improve protein degradation by establishing a syntrophy with hydrogenotrophic
      archaea. To gain a better understanding of the phylogenesis, metabolic
      capabilities and adaptations of these microorganisms, it is of importance to
      better define the role in thermophilic environments and to disclose properties
      not yet investigated. 

PMID- 25764467
TI  - Bacterial community composition and predicted functional ecology of sponges,
      sediment and seawater from the thousand islands reef complex, West Java,
      Indonesia.
AB  - In the present study, we assessed the composition of Bacteria in four biotopes
      namely sediment, seawater and two sponge species (Stylissa massa and Xestospongia
      testudinaria) at four different reef sites in a coral reef ecosystem in West
      Java, Indonesia. In addition to this, we used a predictive metagenomic approach
      to estimate to what extent nitrogen metabolic pathways differed among bacterial
      communities from different biotopes. We observed marked differences in bacterial
      composition of the most abundant bacterial phyla, classes and orders among sponge
      species, water and sediment. Proteobacteria were by far the most abundant phylum
      in terms of both sequences and Operational Taxonomic Units (OTUs). Predicted
      counts for genes associated with the nitrogen metabolism suggested that several
      genes involved in the nitrogen cycle were enriched in sponge samples, including
      nosZ, nifD, nirK, norB and nrfA genes. Our data show that a combined barcoded
      pyrosequencing and predictive metagenomic approach can provide novel insights
      into the potential ecological functions of the microbial communities. Not only is
      this approach useful for our understanding of the vast microbial diversity found
      in sponges but also to understand the potential response of microbial communities
      to environmental change. 

PMID- 25764469
TI  - A glutathione peroxidase (GpoA) plays a role in the pathogenicity of Nautella
      italica strain R11 towards the red alga Delisea pulchra.
AB  - Oxidative bursts are a common mechanism used by higher organisms to defend
      themselves against bacterial attacks, but some pathogenic bacteria have evolved
      resistance mechanisms to counteract this. The role of oxidative stress resistance
      as a virulence trait in macroalgal disease is however unknown. Here, we
      demonstrate that the gene gpoA, encoding for a glutathione peroxidase, is
      important for the oxidative stress response of the macroalgal pathogen Nautella
      italica R11. We also show that a lack of gpoA prevents N. italica R11 from
      inducing a bleaching disease in the red alga Delisea pulchra. These results show
      that a defense against oxidative stress is likely to be an important feature
      enabling pathogenic bacteria to infect macroalgae. 

PMID- 25764468
TI  - Diversity of Miscellaneous Crenarchaeotic Group archaea in freshwater karstic
      lakes and their segregation between planktonic and sediment habitats.
AB  - The Miscellaneous Crenarchaeotic Group (MCG) is an archaeal lineage whose members
      are widespread and abundant in marine sediments. MCG archaea have also been
      consistently found in stratified euxinic lakes. In this work, we have studied
      archaeal communities in three karstic lakes to reveal potential habitat
      segregation of MCG subgroups between planktonic and sediment compartments. In the
      studied lakes, archaeal assemblages were strikingly similar to those of the
      marine subsurface with predominance of uncultured Halobacteria in the plankton
      and Thermoplasmata and MCG in anoxic, organic-rich sediments. Multivariate
      analyses identified sulphide and dissolved organic carbon as predictor variables
      of archaeal community composition. Quantification of MCG using a newly designed
      qPCR primer pair that improves coverage for MCG subgroups prevalent in the
      studied lakes revealed conspicuous populations in both the plankton and the
      sediment. Subgroups MCG-5a and -5b appear as planktonic specialists thriving in
      euxinic bottom waters, while subgroup MCG-6 emerges as a generalist group able to
      cope with varying reducing conditions. Besides, comparison of DNA- and cDNA-based
      pyrotag libraries revealed that rare subgroups in DNA libraries, i.e. MCG-15,
      were prevalent in cDNA-based datasets, suggesting that euxinic, organic-rich
      sediments of karstic lakes provide optimal niches for the activity of some
      specialized MCG subgroups. 

PMID- 25764470
TI  - Diet shapes the gut microbiota of the omnivorous cockroach Blattella germanica.
AB  - The gut microbiota of insects contributes positively to the physiology of its
      host mainly by participating in food digestion, protecting against pathogens, or
      provisioning vitamins or amino acids, but the dynamics of this complex ecosystem
      is not well understood so far. In this study, we have characterized the gut
      microbiota of the omnivorous cockroach Blattella germanica by pyrosequencing the
      hypervariable regions V1-V3 of the 16S rRNA gene of the whole bacterial
      community. Three diets differing in the protein content (0, 24 and 50%) were
      tested at two time points in lab-reared individuals. In addition, the gut
      microbiota of wild adult cockroaches was also analyzed. In contrast to the high
      microbial richness described on the studied samples, only few species are shared
      by wild and lab-reared cockroaches, constituting the bacterial core in the gut of
      B. germanica. Overall, we found that the gut microbiota of B. germanica is highly
      dynamic as the bacterial composition was reassembled in a diet-specific manner
      over a short time span, with no-protein diet promoting high diversity, although
      the highest diversity was found in the wild cockroaches analyzed. We discuss how
      the flexibility of the gut microbiota is probably due to its omnivorous life
      style and varied diets. 

PMID- 25764471
TI  - Systematic investigation of germination responses of Bacillus subtilis spores in
      different high-salinity environments.
AB  - High-salinity environments play an increasingly important role in ecology
      regarding soil salinization due to human-induced processes, but also need to be
      considered in terms of natural soil desiccation and extreme habitats. It has been
      shown previously that spore germination of the ubiquitous soil bacterium Bacillus
      subtilis is detrimentally affected by the presence of high NaCl concentrations,
      but the underlying mechanisms and effects of other salts remained obscure. To
      address these two points, we performed a systematic analysis with 32 different
      salts using spectrophotometric and microscopic methods. It could be shown that
      inhibitory strength varies considerably among different salts. Although osmotic
      effects seem to play an important role, ionic composition and concentration
      (especially of the anion) as well as chemical properties seem to be decisive for
      the extent of germination inhibition. At the current state of knowledge, fluxes
      of ions, Ca(2+)-DPA and water are likely affected by all salts, whereas the exact
      inhibition mechanism of each salt might further depend on the respective
      properties of the involved ions. Hence, the observed inhibition likely is a
      result of several phenomena interacting with each other. Altogether this study
      highlights the complex impact of ionic environments on the life cycle of spore
      formers. 

PMID- 25764472
TI  - Wolbachia in Neotropical terrestrial isopods.
AB  - Despite Wolbachia being widespread among terrestrial isopods, studies on this
      symbiotic relationship are still incipient in the Neotropical region. The aims of
      the present study were to investigate the presence and prevalence of Wolbachia in
      natural populations of terrestrial isopod species in South America, and to
      analyze the diversity and phylogenetic relationships of Wolbachia strains. A
      total of 1172 individuals representing 11 families and 35 species were analyzed.
      We observed distinct evolutionary scenarios according to the geographical origins
      of the species: strains harbored by most of the introduced species belong to the
      Oniclade in supergroup B and are identical to those found in their original
      ecozone (i.e. Palearctic). On the other hand, the strains found in native
      Neotropical terrestrial isopods showed low prevalence, high diversity and none of
      them belonged to the Oniclade, although most belonged to supergroup B. The
      dynamics of infection in Neotropical species seems to be the result of several
      events of loss and acquisition of the bacteria, which refutes the hypothesis of
      an ancestral acquisition of Wolbachia in Oniscidea. The presence of strains from
      supergroups A and F was also detected for the first time in terrestrial isopods,
      revealing a Wolbachia diversity previously unknown for this group of host. 

PMID- 25764473
TI  - Adverse Life Experience and Psychological Distress in Adolescence: Moderating and
      Mediating Effects of Emotion Regulation and Rumination.
AB  - The current study tested whether emotion regulation and rumination moderated
      and/or mediated the relationship between accumulated adverse life experience and
      psychological distress in adolescence. In class, Australian high school students
      (n = 2637, 12-18 years, 68% female) from 41 schools completed well-validated
      measures of adverse life experience, emotion regulation, rumination and
      psychological distress, and were followed up 1 year later (n = 1973, 75%
      retention rate). Adjusting for age, gender and baseline psychological distress,
      adverse life experience predicted psychological distress 1 year later. Expressive
      suppression and rumination were positively associated with psychological
      distress. Cognitive reappraisal was negatively associated with psychological
      distress and moderated the relationship between adverse life experience and
      psychological distress. This relationship was also partially mediated by
      cognitive reappraisal, expressive suppression and rumination. Promoting cognitive
      reappraisal and minimizing expressive suppression and rumination may be useful
      strategies to improve mental health for adolescents who have experienced adverse
      life events. Future research should examine whether adolescents who have
      experienced adverse life events can be trained in effective emotion regulation
      strategies and whether this training can prevent development of psychological
      maladjustment. Copyright (c) 2015 John Wiley & Sons, Ltd.

PMID- 25764474
TI  - Fear of hypoglycaemia in adults with Type 1 diabetes: results from Diabetes MILES
      - The Netherlands.
AB  - AIMS: To examine sociodemographic, clinical and psychological factors associated
      with fear of hypoglycaemia in adults with Type 1 diabetes. METHODS: Data were
      obtained from Diabetes MILES - The Netherlands, an online self-report national
      survey. This cross-sectional analysis focused on participants with Type 1
      diabetes who completed the 18-item Hypoglycaemia Fear Survey - Second Version
      Worry subscale (HFS-II-W; possible total score range 0-72, higher scores
      indicating higher fear) (n = 288). To explore correlates of fear of
      hypoglycaemia, a hierarchical linear regression analysis was performed in
      participants with full data on sociodemographic, clinical and psychological
      factors (n = 232; younger and more highly educated than those excluded). RESULTS:
      HFS-II-W mean score was 11.1 +/- 11.1. Gender, age, education and having a
      partner (model 1) were not associated with fear of hypoglycaemia. In model 2,
      history of severe hypoglycaemia (irrespective of number of events) was associated
      with (greater) fear of hypoglycaemia, whereas diabetes duration, pump therapy and
      HbA1c were not. Type D personality was positively correlated (model 3), as were
      symptoms of depression, but not anxiety (model 4). Adding loneliness (model 5)
      did not improve the model. The fully adjusted analysis showed that fear of
      hypoglycaemia was associated with depressive symptoms (beta = 0.38, P < 0.001)
      and history of hypoglycaemia (1-2 events: beta = 0.30, P < 0.001; >= 3 events:
      beta = 0.19, P = 0.002). Total explained variance was 23%. CONCLUSIONS:
      Depressive symptoms and history of hypoglycaemia are associated with fear of
      hypoglycaemia in adults with Type 1 diabetes. These factors may help to identify
      people with excessive fear, who may particularly benefit from interventions to
      reduce hypoglycaemia risk and worries.

PMID- 25764475
TI  - The Role of 3T Magnetic Resonance Imaging for Targeting the Human Subthalamic
      Nucleus in Deep Brain Stimulation for Parkinson Disease.
AB  - BACKGROUND: Chronic stimulation of the human subthalamic nucleus (STN) is
      gradually becoming accepted as a long-term therapeutic option for patients with
      advanced Parkinson disease (PD). 3Tesla (T) magnetic resonance imaging (MRI)
      improves contrast resolution in basal ganglia nuclei containing high levels of
      iron, because of magnetic susceptibility effects that increase significantly as
      the magnetic field gets higher. This phenomenon can be used for better
      visualization of the STN and may reduce the time necessary for detailed
      microrecording (MER) mapping, increasing surgery efficacy and lowering morbidity.
      OBJECTIVE: The objective of this retrospective study is to analyze a population
      of 20 deep brain stimulation (DBS) electrode implanted patients with PD divided
      into two groups in which different targeting methods were used. METHODS: Mean age
      was 56 years (range 37 to 69 years). Mean disease duration was 11.6 years. Mean
      follow-up was 12 months (range 6 to 36 months). Patients were divided into two
      groups: Group A contained 6 patients who underwent STN targeting using 1T
      stereotactic (T1w + T2w) MRI plus STN indirect atlas derived targeting. Group B
      consisted of 14 patients who underwent STN targeting using 3T nonstereotactic
      (T2w) MRI fused with 1T T1w stereotactic MRI and STN direct targeting. For
      statistical analysis, we compared (five different parameters in both (matched)
      groups: Unified Parkinson's disease rating scale (UPDRS) score reduction
      (medication off before surgery against stimulation on/medication off after
      surgery), postoperative drug reduction, duration of surgery, the "central
      preoperative track" chosen as final implantation track during surgery, and
      correspondence between the targeted STN and the intraoperative neurophysiologic
      data. RESULTS: Mean UPDRS III score reduction (medication off/stimulation on
      versus preoperative medication off) was 69% in Group A and 74% in Group B (p =
      0.015, log-rank test) respectively. Postoperatively, antiparkinsonian treatment
      was reduced by 66% in Group A and 75% in Group B (p = 0.006, log-rank test). The
      preoperative "central" track (which corresponds to ideal STN targeting) proved to
      be the most clinically effective in 2/12 leads for Group A versus 21/28 for Group
      B (p < 0.001).Neurophysiologic data confirmed these results; the hypothetical
      target was confirmed by MER data in 76% of tracks in Group A, and in 75% of
      tracks in Group B (p < 0.001, univariate and multivariate analysis). CONCLUSION:
      3T MRI appears to be a useful tool in STN-DBS preoperative targeting.
      Neurophysiologic testing remains fundamental to determine lead deepness (and
      prevent clinical side effects.

PMID- 25764476
TI  - AtLa1 protein initiates IRES-dependent translation of WUSCHEL mRNA and regulates
      the stem cell homeostasis of Arabidopsis in response to environmental hazards.
AB  - Plant stem cells are hypersensitive to environmental hazards throughout their
      life cycle, but the mechanism by which plants safeguard stem cell homeostasis in
      response to environmental hazards is largely unknown. The homeodomain
      transcription factor WUSCHEL (WUS) protein maintains the stem cell pool in the
      shoot apical meristem of Arabidopsis. Here, we demonstrate that the translation
      of WUS mRNA is directed by an internal ribosomal entry site (IRES) located in the
      5'-untranslated region. The AtLa1 protein, an RNA-binding factor, binds to the 5'
      untranslated region and initiates the IRES-dependent translation of WUS mRNA.
      Knockdown of AtLa1 expression represses the WUS IRES-dependent translation and
      leads to the arrest of growth and development. The AtLa1 protein is mainly
      located in the nucleoplasm. However, environmental hazards promote the nuclear-to
      cytoplasmic translocation of the AtLa1 protein, which further enhances the IRES
      dependent translation of WUS mRNA. Genetic evidence indicates that the WUS
      protein increases the tolerance of the shoot apical meristem to environmental
      hazards. Based on these results, we conclude that the stem cell niche in
      Arabidopsis copes with environmental hazards by enhancing the IRES-dependent
      translation of WUS mRNA under the control of the AtLa1 protein. 

PMID- 25764477
TI  - A recombinant canine distemper virus expressing a modified rabies virus
      glycoprotein induces immune responses in mice.
AB  - Canine distemper virus (CDV) and rabies virus (RV) are two important pathogens of
      the dog. CDV, a member of the morbillivirus genus, has shown promise as an
      expression vector. The glycoprotein from RV is a main contributor to protective
      immunity and capable of eliciting the production of virus-neutralizing
      antibodies. In this study, we recovered an attenuated strain of canine distemper
      virus and constructed a recombinant virus, rCDV-RV-G, expressing a modified
      (R333Q) rabies virus glycoprotein (RV-G) of RV Flury strain LEP. RV-G expression
      by the recombinant viruses was confirmed. Furthermore, G was proved to be
      incorporated into the surface of CDV particles. While replication of the
      recombinant virus was slightly reduced compared with the parental CDV, it stably
      expressed the RV-G over ten serial passages. Inoculation of mice induced specific
      neutralizing antibodies against both RV-G and CDV. Therefore, the rCDV-RV-G has
      the potential as a vaccine that may be used to control rabies virus infection in
      dogs and other animals. 

PMID- 25764478
TI  - A work time study analysing differences in resource use between psychiatric
      inpatients.
AB  - PURPOSE: Judgement about the adequacy of reimbursement schemes requires an
      understanding of differences in resource use between patient groups. The aim of
      this study was to analyse staff time allocation of psychiatrists, psychologists
      and nurses in inpatient mental health care and to use these data to analyse
      differences in per diem resource use between patient groups. METHODS: A self
      reporting work-sampling study was carried out at a psychiatric teaching hospital.
      All of 36 psychiatrists, 23 psychologists and 106 nurses involved in clinical
      care during the study period participated in a two-week measurement of their work
      time. RESULTS: A total of 20,380 observations were collected, representing about
      10,190 h of work or 6.2 full-time-equivalent years. The average resource use in
      minutes of staff time per patient day was 227 min, representing 138 <euro> of
      staff costs. The most resource intensive care was provided at the Psychiatric
      Intensive Care Unit and for geriatric patients with 334 and 266 min per patient
      day (192 and 162 <euro>), respectively. The least resource intensive care was
      provided for patients with substance-related disorders (197 min, 116 <euro>).
      Substantial shares of clinical work time were dedicated to tasks without patient
      contact (58 %). Nursing time was the main driver of total resource use,
      representing 70 % of staff time and 60 % of costs. CONCLUSION: Presented
      differences in per diem resource use should inform discussions about the adequacy
      of reimbursement schemes. Tasks in the absence of the patient, such as
      documentation and administration, should be reduced to free resources for direct
      patient care.

PMID- 25764479
TI  - The selective dopamine D3 receptor antagonist SB-277011-A significantly decreases
      binge-like consumption of ethanol in C57BL/J6 mice.
AB  - The authors show that the dopamine D3 antagonist SB-277011-A consistently and
      persistently decrease binge-like EtOH consumption at 30 mg/kg and it decreases
      binge-like consumption on days 3, 7, 9, and 11-13 at 15 mg/kg. These findings
      suggest that the brain's D3 receptor may also be involved in not only ethanol
      reward but binge drinking as well.

PMID- 25764480
TI  - Osteoporosis and bisphosphonate-related osteonecrosis in a dental school implant
      patient population.
AB  - PURPOSE: Studies have demonstrated an inconsistent association between implant
      failure and bone mineral density. The prevalence of osteoporosis in US adults has
      been reported to range from 5% to 10% in women and from 2% to 4% in men. The
      prevalence of bisphosphonate (BP)-related osteonecrosis of the jaw (BRONJ) has
      been reported to range from 0% to 4.3% of patients taking oral BPs. The purpose
      of this study was to calculate the risk of dental implant loss and the incidence
      of BRONJ in patients with osteoporosis at the University of Kentucky College of
      Dentistry (UKCD). MATERIALS AND METHODS: This study analyzed data collected from
      patients who had implants placed between 2000 and 2004 at UKCD. Data were
      gathered from patient interviews regarding implant survival and patient
      satisfaction parameters, and interviews were conducted either chairside at a
      scheduled maintenance appointment or by telephone interview. RESULTS: Among 203
      patients who received 515 implants, the prevalence of osteoporosis was 23.3% for
      women and 1.2% for men. None of the 20 patients who reported a history of oral BP
      use exhibited BRONJ, and there were no implant failures in patients with a
      history of osteoporosis. CONCLUSIONS: In this study, osteoporosis conferred no
      risk of implant failure, and oral BP therapy was not associated with BRONJ.

PMID- 25764481
TI  - Buccolingual implant position and vertical abutment finish line geometry: two
      strictly related factors that may influence the implant esthetic outcome.
AB  - PURPOSE: Three-dimensional implant positioning has always been a highly debated
      topic especially in the esthetic zone due to many problems related to buccal bone
      resorption. A new concept in implant position, dictated by changing the abutment
      finish line, is presented in the following article. MATERIALS AND METHODS: The
      actual guidelines on implant position agree that in the bucco-palatal dimension,
      the implant should be placed more toward the palatal preserving at least 2 mm of
      buccal bone. However, changing the abutment finish line geometry from horizontal
      to vertical, the authors' geometry of choice, the surgical approach in the bucco
      palatal direction has been modified accordingly to ensure final restorations that
      will guarantee long-term soft tissue stability. RESULTS: The emergence angle of
      the natural teeth has been the authors' guide to establish the implant position
      which should be located with the long axis of the implant corresponding to the
      incisal edge of the future restoration. Observation of the clinical results in
      the past years strongly supports this approach. CONCLUSIONS: The surgical and
      prosthetic concepts described in this article allow the clinician to recreate a
      pleasant and natural-looking esthetics while the patient can easily maintain a
      proper hygiene around the implant. However, despite the promising clinical
      results obtained by the authors, further clinical and randomized researches
      should be realized to validate the above-proposed approach.

PMID- 25764483
TI  - Comparison of low level laser and arginine-calcium carbonate alone or combination
      in the treatment of dentin hypersensitivity: a randomized split-mouth clinical
      study.
AB  - OBJECTIVE: This study aimed to compare the efficacy of low-level laser (LLL) and
      desensitizing paste (DP) containing 8% arginine-calcium carbonate, in the
      treatment of dentin hypersensitivity (DH) and also to determine whether their
      combined application would improve the efficacy of the treatment. BACKGROUND
      DATA: There are various options for the treatment of DH; however, superiority of
      one method over others alone has not been currently demonstrated. MATERIALS AND
      METHODS: Twenty-one patients with 156 teeth affected by DH were included in the
      study. Selected teeth were randomly divided into five groups: LLL, DP, laser
      followed by DP (LLL+DP), DP followed by laser (DP+LLL) applied to one of the
      quadrants, and a control group, consisting of a randomly selected additional
      tooth in one of the quadrants. Teeth were irradiated by the 685 nm diode laser
      treatment with 25 mW at 9 Hz for 100sec at 1 cm(2) area (2J/cm(2)) in interrupted
      mode. Pain response to evaporative stimulus was quantified on a visual analogue
      scale (VAS) over a 90-day period. RESULTS: All four treatment groups experienced
      significant and persistent decrease in the mean VAS score immediately post
      treatment until the end of the study, whereas the placebo group had high VAS
      scores throughout the study. On day 90, percent reduction in VAS scores was 72%
      for LLL, 65.4% for DP, 54.6% for LLL+DP, and 69.6% for DP+LLL, whereas the
      placebo group showed an increase of 7.8%. CONCLUSIONS: The application of either
      LLL or DP containing 8% arginine-calcium carbonate appears to be effective in
      decreasing DH. However, their combined use does not improve the efficacy beyond
      what is attainable with either treatment alone.

PMID- 25764484
TI  - Pneumomediastinum as a complication of critical pertussis.
AB  - BACKGROUND AND AIMS: Pertussis is a common and potentially serious disease
      affecting mainly infants and young children. In its non-classic presentation,
      pertussis can be clinically indistinguishable from other respiratory illnesses.
      Pertussis today often remains underdiagnosed in adults. Our aims was to report a
      complicated cases of pertussis. RESULTS: A case of serologically confirmed
      pertussis occurred in an 18-year-old man presenting with pneumomediastinum,
      subcutaneous emphysema in the neck and chest, and persistent attacks of coughing
      with apnea that required treatment in the intensive care unit. CONCLUSION:
      Pneumomediastinum and subcutaneous emphysema have never been described in adult
      patients with pertussis. Physicians should be aware that patients presenting with
      persistent cough and pneumomediastinum may have pertussis and include this in
      their differential diagnosis.

PMID- 25764482
TI  - Vision-Related Quality-of-Life Outcomes in the Mycotic Ulcer Treatment Trial I: A
      Randomized Clinical Trial.
AB  - IMPORTANCE: Given the limitations in health care resources, quality-of-life
      measures for interventions have gained importance. OBJECTIVE: To determine
      whether vision-related quality-of-life outcomes were different between the
      natamycin and voriconazole treatment arms in the Mycotic Ulcer Treatment Trial I,
      as measured by an Indian Vision Function Questionnaire. DESIGN, SETTING, AND
      PARTICIPANTS: Secondary analysis (performed October 11-25, 2014) of a double
      masked, multicenter, randomized, active comparator-controlled, clinical trial at
      multiple locations of the Aravind Eye Care System in South India that enrolled
      patients with culture- or smear-positive filamentous fungal corneal ulcers who
      had a baseline visual acuity of 20/40 to 20/400 (logMAR of 0.3-1.3).
      INTERVENTIONS: Study participants were randomly assigned to topical voriconazole,
      1%, or topical natamycin, 5%. MAIN OUTCOMES AND MEASURES: Subscale score on the
      Indian Vision Function Questionnaire from each of the 4 subscales (mobility,
      activity limitation, psychosocial impact, and visual function) at 3 months.
      RESULTS: A total of 323 patients were enrolled in the trial, and 292 (90.4%)
      completed the Indian Vision Function Questionnaire at 3 months. The majority of
      study participants had subscale scores consistent with excellent function. After
      adjusting for baseline visual acuity and organism, we found that study
      participants in the natamycin-treated group scored, on average, 4.3 points (95%
      CI, 0.1-8.5) higher than study participants in the voriconazole-treated group (P
      = .046). In subgroup analyses looking at ulcers caused by Fusarium species and
      adjusting for baseline best spectacle-corrected visual acuity, the natamycin
      treated group scored 8.4 points (95% CI, 1.9-14.9) higher than the voriconazole
      treated group (P = .01). Differences in quality of life were not detected for
      patients with Aspergillus or other non-Fusarium species as the causative organism
      (1.5 points [95% CI, -3.9 to 6.9]; P = .52). CONCLUSIONS AND RELEVANCE: We found
      evidence of improvement in vision-related quality of life among patients with
      fungal ulcers who were randomly assigned to natamycin compared with those
      randomly assigned to voriconazole, and especially among patients with Fusarium
      species as the causative organism. Incorporation of quality-of-life measures in
      clinical trials is important to fully evaluate the effect of the studied
      interventions. TRIAL REGISTRATION: clinicaltrials.gov Identifier:NCT00996736.

PMID- 25764485
TI  - Determination of the optimal dose reduction level via iterative reconstruction
      using 640-slice volume chest CT in a pig model.
AB  - AIM: To determine the optimal dose reduction level of iterative reconstruction
      technique for paediatric chest CT in pig models. MATERIALS AND METHODS: 27 infant
      pigs underwent 640-slice volume chest CT with 80kVp and different mAs. Automatic
      exposure control technique was used, and the index of noise was set to SD10
      (Group A, routine dose), SD12.5, SD15, SD17.5, SD20 (Groups from B to E) to
      reduce dose respectively. Group A was reconstructed with filtered back projection
      (FBP), and Groups from B to E were reconstructed using iterative reconstruction
      (IR). Objective and subjective image quality (IQ) among groups were compared to
      determine an optimal radiation reduction level. RESULTS: The noise and signal-to
      noise ratio (SNR) in Group D had no significant statistical difference from that
      in Group A (P = 1.0). The scores of subjective IQ in Group A were not
      significantly different from those in Group D (P>0.05). There were no obvious
      statistical differences in the objective and subjective index values among the
      subgroups (small, medium and large subgroups) of Group D. The effective dose (ED)
      of Group D was 58.9% lower than that of Group A (0.20+/-0.05mSv vs 0.48+/
      0.10mSv, p <0.001). CONCLUSIONS: In infant pig chest CT, using iterative
      reconstruction can provide diagnostic image quality; furthermore, it can reduce
      the dosage by 58.9%.

PMID- 25764486
TI  - Development of advanced macrosphelides: potent anticancer agents.
AB  - Synthetic approaches to macrosphelide derivatives, based on medicinal chemistry,
      are summarized. This review contains conventional medicinal chemistry approaches,
      combinatorial chemistry, fluorous tagging techniques and affinity chromatography
      preparation. In addition, advances in their apoptosis-inducing activities are
      also included.

PMID- 25764487
TI  - New sesquiterpenoids from Ambrosia artemisiifolia L.
AB  - A new pseudoguaianolide 1 and two new guaiane-type sesquiterpene glucosides 2 and
      3, were isolated from the aerial parts of Ambrosia artemisiifolia L together with
      two known sesquiterpene dilactones 4 and 5. The new compounds were determined on
      the basis of spectroscopic and chemical methods to be 3beta-acetoxy-4beta-hydroxy
      1alpha,7alpha, 10beta,11alphaH-pseudoguaia-12,8beta-olide (1),
      1beta,7beta,9beta,10beta,13alphaH-guaia-4(5)-en-12,6beta-olide 9-O-beta-d
      glucoside (2) and 4beta-hydroxy-1alpha,5alpha,7alpha,9alphaH-guaia-10(14),11(13)
      dien-12-acid 9-O-beta-d-glucoside (3). The isolated compounds were evaluated for
      cytotoxicity against human promyelocytic leukemia HL-60 cell lines in vitro, but
      were all inactive.

PMID- 25764488
TI  - The effect of number and position of P=O/P=S bridging units on cavitand
      selectivity toward methyl ammonium salts.
AB  - The present work reports the synthesis and complexation properties of five mixed
      bridge P=O/P=S cavitands toward N,N-methyl butyl ammonium chloride (1) as
      prototype guest. The influence of number and position of P=O and P=S groups on
      the affinity of phosphonate cavitands toward 1 is assessed via ITC titrations in
      DCE as solvent. Comparison of the resulting Kass values, the enthalpic and
      entropic contributions to the overall binding with those of the parent
      tetraphosphonate Tiiii and tetrathiophosphonate TSiiii cavitands allows one to
      single out the simultaneous dual H-bond between the cavitand and the salt as the
      major player in complexation.

PMID- 25764489
TI  - Inhibitory effect of Duabanga grandiflora on MRSA biofilm formation via
      prevention of cell-surface attachment and PBP2a production.
AB  - Formation of biofilms is a major factor for nosocomial infections associated with
      methicillin-resistance Staphylococcus aureus (MRSA). This study was carried out
      to determine the ability of a fraction, F-10, derived from the plant Duabanga
      grandiflora to inhibit MRSA biofilm formation. Inhibition of biofilm production
      and microtiter attachment assays were employed to study the anti-biofilm activity
      of F-10, while latex agglutination test was performed to study the influence of F
      10 on penicillin-binding protein 2a (PBP2a) level in MRSA biofilm. PBP2a is a
      protein that confers resistance to beta-lactam antibiotics. The results showed
      that, F-10 at minimum inhibitory concentration (MIC, 0.75 mg/mL) inhibited
      biofilm production by 66.10%; inhibited cell-surface attachment by more than 95%;
      and a reduced PBP2a level in the MRSA biofilm was observed. Although ampicilin
      was more effective in inhibiting biofilm production (MIC of 0.05 mg/mL, 84.49%)
      compared to F-10, the antibiotic was less effective in preventing cell-surface
      attachment. A higher level of PBP2a was detected in ampicillin-treated MRSA
      showing the development of further resistance in these colonies. This study has
      shown that F-10 possesses anti-biofilm activity, which can be attributed to its
      ability to reduce cell-surface attachment and attenuate the level of PBP2a that
      we postulated to play a crucial role in mediating biofilm formation.

PMID- 25764490
TI  - Two new phenolic glucosides from Lagerstroemia speciosa.
AB  - Two new phenolic glucosides, 1-O-benzyl-6-O-E-caffeoyl-beta-d-glucopyranoside and
      1-O-(7S,8R)-guaiacylglycerol-(6-O-E-caffeoyl)-beta-d-glucopyranoside, were
      isolated from the aerial parts of Lagerstroemia speciosa, along with ten known
      compounds. The structures of the isolated compounds were determined based on 1D-
      and 2D-NMR, Q-TOF MS and optical rotation spectroscopic data. All of the
      compounds showed moderate inhibitory activities against nitric oxide production
      in lipopolysaccharide-treated RAW264.7 cells, with IC50 values of 69.5-83.3 MUM.

PMID- 25764491
TI  - Multigram synthesis and in vivo efficacy studies of a novel multitarget anti
      Alzheimer's compound.
AB  - We describe the multigram synthesis and in vivo efficacy studies of a donepezil
      huprine hybrid that has been found to display a promising in vitro multitarget
      profile of interest for the treatment of Alzheimer's disease (AD). Its synthesis
      features as the key step a novel multigram preparative chromatographic resolution
      of intermediate racemic huprine Y by chiral HPLC. Administration of this compound
      to transgenic CL4176 and CL2006 Caenorhabditis elegans strains expressing human
      Abeta42, here used as simplified animal models of AD, led to a significant
      protection from the toxicity induced by Abeta42. However, this protective effect
      was not accompanied, in CL2006 worms, by a reduction of amyloid deposits. Oral
      administration for 3 months to transgenic APPSL mice, a well-established animal
      model of AD, improved short-term memory, but did not alter brain levels of Abeta
      peptides nor cortical and hippocampal amyloid plaque load. Despite the clear
      protective and cognitive effects of AVCRI104P4, the lack of Abeta lowering effect
      in vivo might be related to its lower in vitro potency toward Abeta aggregation
      and formation as compared with its higher anticholinesterase activities. Further
      lead optimization in this series should thus focus on improving the anti
      amyloid/anticholinesterase activity ratio.

PMID- 25764492
TI  - Comparison between whole-body vibration, light-emitting diode, and cycling warm
      up on high-intensity physical performance during sprint bicycle exercise.
AB  - The purpose of this study was to compare the effects of light-emitting diode
      (LED) irradiation and whole-body vibration (WBV) delivered either in isolation or
      combination (LED + WBV), warm-up (WU), and a control (C) treatment on performance
      during a sprint bicycle exercise. Ten cyclists performed a 30-second sprint cycle
      test under these conditions. The LED light was applied at 4 points bilaterally.
      Whole-body vibration consisted of 5 minutes of squats associated with WBV. LED +
      WBV consisted of WBV followed by LED therapy. Warm-up consisted of 17 minutes of
      moderate-intensity bicycle exercise. Control consisted of 10 minutes at rest.
      Blood lactate (BL) and ammonia (BA) levels and skin temperature (ST) were
      determined. Peak power (842 +/- 117 vs. 800 +/- 106 vs. 809 +/- 128 W [p = 0.02
      and p = 0.01]), relative power (12.1 +/- 1.0 vs. 11.5 +/- 0.9 vs. 11.6 +/- 1.0
      W.kg [p = 0.02 and p = 0.02]), and relative work (277 +/- 23 vs. 263 +/- 24 vs.
      260 +/- 23 J.kg [p = 0.02 and p = 0.003]) were higher in the WU group compared
      with the control and LED groups. In the LED + WBV group, peak (833 +/- 115 vs.
      800 +/- 106 W [p = 0.02]) and relative (11.9 +/- 0.9 vs. 11.5 +/- 0.9 W.kg [p =
      0.02]) power were higher than those in the control group, and relative work (272
      +/- 22 vs. 260 +/- 23 J.kg [p = 0.02]) were improved compared with the LED group.
      There were no differences for BL, BA, and ST. The findings of this study
      confirmed the effectiveness of a warm-up as a preparatory activity and
      demonstrated that LED + WBV and WBV were as effective as WU in improving cyclist
      performance during a sprint bicycle exercise.

PMID- 25764493
TI  - The effect of two generic aerobic interval training methods on laboratory and
      field test performance in soccer players.
AB  - The purpose of this study was to compare the effects of 2 generic aerobic
      training models, based on peak running velocity in Carminatti's test (PVT-CAR) in
      U-20 elite soccer players. Seventeen soccer players (age: 17.9 +/- 1.0 years;
      178.6 +/- 5.0 cm; 73.6 +/- 6.6 kg; 11.1 +/- 1.3%) from a team competing in a
      national junior league took part in the study. The athletes performed a series of
      pre- and posttraining tests (incremental test on a treadmill to determine the
      maximal oxygen uptake [(Equation is included in full-text article.)], velocity at
      maximal oxygen uptake [(Equation is included in full-text article.)], the lactate
      threshold [LT], and T-CAR). The interval training models applied were with 180
      degrees  direction change (T12:12; n = 9) and without direction change (T6:6; n =
      8). No significant interaction (time vs. group) was observed for the majority of
      variables analyzed (p > 0.05), although significant main effects in time were
      evident regarding peak treadmill velocity (PVTREAD) (F = 56.3, p < 0.0001),
      (Equation is included in full-text article.)(F = 35.8, p < 0.0001), LT (F = 57.7,
      p < 0.0001), and PVT-CAR (F = 52.9, p < 0.0001). Moreover, there was no
      significant change in (Equation is included in full-text article.)between pre and
      posttraining period (F = 4.26, p = 0.056) in both training groups. Thus, it can
      be concluded that the prescribed training with and without direction change in
      the intensity of the PVT-CAR increases the PVTREAD, the (Equation is included in
      full-text article.), the LT, and the PVT-CAR similarly.

PMID- 25764494
TI  - Influence of Blood Flow Restriction During Low-Intensity Resistance Exercise on
      the Postexercise Hypotensive Response.
AB  - Low-intensity resistance exercise (RE) combined with blood flow restriction (BFR)
      has been shown to promote similar increases in strength and hypertrophy as
      traditional high-intensity RE without BFR. However, the effect of BFR on the
      acute postexercise hypotensive response has received limited examination.
      Therefore, the purpose of this study was to compare high-intensity exercise (HIE)
      vs. low-intensity RE with BFR on the postexercise hypotensive response in
      normotensive young subjects. Fifteen men (age: 23.4 +/- 3.4 years) performed the
      following 2 experimental protocols in randomized order: (a) 3 sets of biceps
      curls (BCs) at 80% of 1 repetition maximum (RM) and 120-second rest between sets
      (HIE protocol) and (b) 3 sets of BCs at 40% of 1RM with BFR and 60-second rest
      between sets. Analysis of systolic blood pressure (SBP) and diastolic blood
      pressure (DBP) was conducted for 60 minutes after both protocols. The values for
      SBP, DBP, and mean blood pressure (MBP) at baseline and postexercise were not
      significantly different between the HIE vs. the BFR protocol. However, within the
      BFR protocol, significant decreases (p <= 0.05) in SBP occurred at 30 minutes
      (125.86 +/- 9.33 mm Hg) and 40 minutes (125.53 +/- 10.19 mm Hg) after exercise
      when compared with baseline (132.86 +/- 9.12 mm Hg) and significant decreases in
      DBP and MBP occurred at 20 minutes, 30 minutes, and 40 minutes after exercise vs.
      baseline (p <= 0.05). Therefore, we conclude that exercises engaging a relatively
      small amount of muscle mass, such as the BC (or other similar single joint
      exercises), might be performed at a lower intensity with BFR to promote a
      postexercise hypotensive response.

PMID- 25764495
TI  - Wear resistance of the biocompatible phospholipid polymer-grafted highly cross
      linked polyethylene liner against larger femoral head.
AB  - The use of larger femoral heads to prevent the dislocation of artificial hip
      joints has recently become more common. However, concerns about the subsequent
      use of thinner polyethylene liners and their effects on wear rate have arisen.
      Previously, we prepared and evaluated the biological and mechanical effects of a
      novel highly cross-linked polyethylene (CLPE) liner with a nanometer-scaled graft
      layer of poly(2-methacryloyloxyethyl phosphorylcholine) (PMPC). Our findings
      showed that the PMPC-grafted particles were biologically inert and caused no
      subsequent bone resorptive responses and that the PMPC-grafting markedly
      decreased wear in a hip joint simulator. However, the metal or ceramic femoral
      heads used in this previous study had a diameter of 26 mm. Here, we investigated
      the wear-resistance of the PMPC-grafted CLPE liner with a 40-mm femoral head
      during 10 * 10(6) cycles of loading in the hip joint simulator. The results
      provide preliminary evidence that the grafting markedly decreased gravimetric
      wear rate and the volume of wear particles, even when coupled with larger femoral
      heads. Thus, we believe the PMPC-grafting will prolong artificial hip joint
      longevity both by preventing aseptic loosening and by improving the stability of
      articular surface.

PMID- 25764496
TI  - Red-emitting DPSB-based conjugated polymer nanoparticles with high two-photon
      brightness for cell membrane imaging.
AB  - New red-emitting conjugated polymers have been successfully synthesized by
      incorporating classical two-photon absorption (TPA) units, electron-rich units,
      and a small amount of electron-deficient units along the polymer backbones. Water
      dispersible nanoparticles (NPs) based on these polymers were also fabricated for
      applications in two-photon excitation fluorescence imaging of cell membrane.
      Through optimization of the polymer/matrix mass ratio and the initial feed
      concentration of the polymer solution, a high quantum yield (QY) of 24% was
      achieved for the red-emitting NPs in water. TPA cross section and two-photon
      action cross section values of these polymers at 750 nm reached up to 1000 GM and
      190 GM per repeat unit in aqueous media, 2.5 * 10(5) GM and 4.7 * 10(4) GM per
      NP, respectively. Furthermore, these NPs displayed excellent photostability and
      biocompatibility. Their applications as two-photon excitation fluorescence probes
      for cell membrane imaging have been demonstrated in three different cell lines
      with excellent imaging contrast. These results demonstrated that these polymer
      NPs hold great potentials as excellent two-photon excitation fluorescence probes
      in various biological applications. 

PMID- 25764497
TI  - Nocturnal melatonin levels decode daily light environment and reflect seasonal
      states in night-migratory blackheaded bunting (Emberiza melanocephala).
AB  - We proposed two perhaps overlapping hypotheses. Hypothesis 1 examined whether
      daily light information was transduced by a change in the pattern of daily
      melatonin secretion. Hypothesis 2 tested whether the melatonin amplitude peak was
      contingent upon seasonal states. To test these hypotheses, we performed three
      experiments on night migratory blackheaded buntings (Emberiza melanocephala). The
      first two experiments measured plasma melatonin levels in buntings exposed to
      light-dark (LD) cycles, with white and/or blue (450 nm) and red (640 nm) light
      periods differing by about 10-12 fold in the level of illuminance. In birds
      exposed to a 12 h day (white light) at 0.66 W m(-2) (dim) and 7.85 W m(-2)
      (bright) light intensities (experiment 1), night melatonin levels were
      significantly affected by the end of 8-week exposure in the dim, not bright, day
      with buntings showing a bimodal nocturnal melatonin peak. Similarly, in birds on
      13 h days in white, blue and red light periods at 0.028 W m(-2) (dim) and 0.28
      (bright) W m(-2) intensities (experiment 2), mid night melatonin levels were
      significantly higher in red than in the blue or white light periods after 4.5
      weeks of exposure. The third experiment measured plasma melatonin levels in
      buntings that were held under natural light conditions (NDL, 27 degrees N;
      experiment 3A), or exposed to LD cycles (experiment 3B). There were slightly more
      elevated melatonin levels early at night during the spring (photosensitive) than
      during the autumn (photorefractory) migration season, without a difference in
      nocturnal melatonin peak between these two times providing almost similar light
      hours. Similarly, there was no difference in mid night melatonin levels between
      photosensitive and photorefractory buntings subjected to a skeleton photoperiod
      (1L : 11D : 1L : 11D), although melatonin levels were higher in the first than in
      the second 11 h dark phase in photosensitive birds. Overall, these results show
      that (i) nocturnal melatonin levels decode the intensity and wavelength of the
      daily light environment, and (ii) the daily melatonin secretion pattern subtly
      reflects seasonal states in the migratory blackheaded bunting. 

PMID- 25764499
TI  - Teaching in the office.

PMID- 25764498
TI  - Circulating Soluble Fas and Fas Ligand Levels Are Elevated in Children with
      Nonalcoholic Steatohepatitis.
AB  - BACKGROUND: There is an urgent need to develop alternatives to liver biopsy in
      children to diagnose nonalcoholic steatohepatitis (NASH), the aggressive form of
      nonalcoholic fatty liver disease (NAFLD). Increased hepatocyte apoptosis plays a
      central role in the development of NASH. AIMS: To evaluate the plasma levels of
      two markers of apoptosis, soluble Fas (sFas) and soluble Fas ligand (sFasL), in
      children with NAFLD and assess their utility as biomarkers of disease severity.
      METHODS: Children with biopsy-proven NAFLD were included, and blood samples were
      collected. Patients were divided into NASH and "not NASH." We measured plasma
      sFas and sFasL using specific ELISA immunoassays. RESULTS: One hundred and
      seventeen children with NAFLD were recruited. Average age was 12.2 +/- 2.9 years,
      67 % were male, and 58 % had NASH. Patients with NASH had significantly higher
      levels of sFas and sFasL than patients in the "not NASH" group (686.0 +/- 186.5
      pg/mL versus 594.2 +/- 244.9, p = 0.023 for sFas and 324.9 +/- 146.5 pg/mL versus
      221.4 +/- 134.0, p < 0.001 for sFasL). sFasL was found to have higher accuracy
      for predicting the presence of NASH on liver biopsy with an AUC (95 % CI) of
      0.714 (0.618, 0.810). A prediction model, the NASH apoptosis score, was generated
      consisting of plasma sFasL, age, ferritin, transferrin, and triglyceride levels.
      The area under receiver operating characteristic curve was 0.78 (95 % CI 0.0.69,
      0.87). CONCLUSIONS: Markers of the extrinsic pathway of hepatocyte apoptosis are
      elevated in children with NASH. sFasL and the NASH apoptosis score are potential
      novel biomarkers for NASH.

PMID- 25764500
TI  - Bilateral Transposition Lip Flaps: A Novel Single-Stage Reconstruction of Central
      Upper Lip Defects Involving Cupid's Bow.
AB  - IMPORTANCE: Defects of the central upper lip present a challenge. A variety of
      techniques have been described, but most tend to efface the natural contours
      present in the philtrum and the cutaneous-mucosal vermilion border (Cupid's bow).
      Furthermore, the techniques typically require a second-stage procedure to improve
      the upper lip aesthetic. We discuss a novel technique using bilateral
      transposition flaps to reconstruct central defects of the upper lip that violate
      Cupid's bow while maintaining normal aesthetic landmarks in a single stage. The
      mean angle of the transposition flaps was calculated. OBSERVATIONS: A
      retrospective review of 7 patients was performed to identify those who underwent
      reconstruction of central upper lip defects at a Mohs reconstruction referral
      practice. Medical records from January 2009 to December 2013 were evaluated. The
      mean diameter of the final defect was 1.4 cm (range, 1.2-2.1 cm). The mean angle
      of the transposition flaps used was 50 degrees . All defects were closed in a
      single stage with no secondary defect remaining. There was no need for a second
      stage procedure. CONCLUSIONS AND RELEVANCE: The use of bilateral transposition
      flaps is a viable and preferred method for a single-stage reconstruction of the
      Cupid's bow and philtrum in central defects of the upper lip.

PMID- 25764501
TI  - Intraspecific Autochthonous and Allochthonous Resource Use by Zooplankton in a
      Humic Lake during the Transitions between Winter, Summer and Fall.
AB  - Seasonal patterns in assimilation of externally produced, allochthonous, organic
      matter into aquatic food webs are poorly understood, especially in brown-water
      lakes. We studied the allochthony (share biomass of terrestrial origin) in
      cladoceran, calanoid and cyclopoid micro-crustacean zooplankton from late winter
      to fall during two years in a small humic lake (Sweden). The use of allochthonous
      resources was important for sustaining a small population of calanoids in the
      water column during late winter. However, in summer the calanoids shifted to 100%
      herbivory, increasing their biomass several-fold by making efficient use of the
      pelagic primary production. In contrast, the cyclopoids and cladocerans remained
      at high levels of allochthony throughout the seasons, both groups showing the
      mean allochthony of 0.56 (range in mean 0.17-0.79 and 0.34-0.75, for the
      respective group, depending on model parameters). Our study shows that
      terrestrial organic matter can be an important resource for cyclopoids and
      cladocerans on an annual basis, forming a significant link between terrestrial
      organic matter and the higher trophic levels of the food web, but it can also be
      important for sustaining otherwise herbivorous calanoids during periods of low
      primary production in late winter. 

PMID- 25764502
TI  - The influence of carbon sources on the expression of the recA gene and
      genotoxicity detection by an Acinetobacter bioreporter.
AB  - Bacterial whole-cell bioreporters are practical and reliable analytical tools to
      assess the toxicity and bioavailability of environmental contaminants, yet
      evidence has shown that their performance could be affected by different carbon
      sources. This paper evaluated the influence of carbon sources on the recA gene
      (ACIAD1385) in a DNA damage-inducible recA::luxCDABE Acinetobacter bioreporter
      and optimized the induction conditions for its practical application in
      environmental monitoring. Different carbon sources, including LB, potassium
      acetate (MMA), sodium citrate (MMC), sodium pyruvate (MMP), and sodium succinate
      (MMS), significantly influenced (p < 0.05) the bioluminescence intensity of the
      genotoxicity bioreporter. A reverse transcription quantitative PCR (RT-qPCR)
      showed the different expression levels of the DNA damage-inducible gene recA (p <
      0.05), suggesting that carbon sources influenced the DNA damage response in the
      Acinetobacter bioreporter at the transcriptional level. Additionally, proteomic
      analysis identified 122 proteins that were differentially expressed after
      exposure to mitomycin C in defined media and LB, and 5 of them were related to
      the DNA damage response, indicating the effects of carbon sources on the DNA
      damage response in Acinetobacter at the translational level. The repression
      effect caused by the rich medium, LB, was possibly related to the mechanism of
      carbon catabolite repression. Our results suggest that the practical application
      of Acinetobacter bioreporters to the genotoxicity assessment of polycyclic
      aromatic hydrocarbon (PAH)-contaminated soils could be significantly improved by
      using a standard medium of defined composition, as this could increase their
      sensitivity. 

PMID- 25764503
TI  - Effect of frailty on short- and mid-term outcomes in vascular surgical patients.
AB  - BACKGROUND: Frailty is a multidimensional vulnerability resulting from age
      associated decline. The impact of frailty on outcomes was assessed in a cohort of
      vascular surgical patients. METHODS: The study included patients aged over 65
      years with length of hospital stay (LOS) greater than 2 days, who were admitted
      to a tertiary vascular unit over a single calendar year. Demographics, mode of
      admission, diagnosis, mortality, LOS and discharge destination were recorded, as
      well as a variety of frailty-specific characteristics. The impact of frailty on
      LOS, discharge destination, survival and readmission rate was assessed using
      multivariable regression techniques. The ability of the models to predict these
      outcomes was also assessed. RESULTS: In total, 413 patients of median age 77
      years were followed for a median of 18 (range 12-24) months. The in-hospital, 3-
      and 12-month mortality rates were 3.6, 8.5 and 13.8 per cent respectively.
      Receiver operating characteristic (ROC) curve analysis revealed that frailty
      based regression models were excellent predictors of 12-month mortality (area
      under the ROC curve (AUC) = 0.81), prolonged LOS (AUC = 0.79) and discharge to a
      care institution (AUC = 0.84). A simple additive frailty score using six key
      features retained strong predictive power for 12-month mortality (AUC = 0.83),
      discharge to a care institution (AUC = 0.78) and prolonged LOS (AUC = 0.74). This
      frailty score was also strongly associated with readmission rates (P < 0.001).
      CONCLUSION: Frailty in vascular surgery patients predicts a multiplicity of
      poorer outcomes. Optimal management should include identification of at-risk
      patients and treatment of modifiable risk factors.

PMID- 25764504
TI  - Biodiversity governance: a Tower of Babel of scales and cultures.
AB  - The recently created Intergovernmental Platform on Biodiversity and Ecosystem
      Services (IPBES), originally focused on multilateral and global issues, is
      shifting its focus to address local issues and to include in its assessments
      local stakeholders and indigenous and traditional systems of knowledge.
      Acknowledging that full biodiversity governance is unavoidably rooted in
      participation of local actors and their problems and knowledge, we suggest that
      to deal successfully with the complexity and diversity of local issues, including
      indigenous knowledge systems, IPBES must recognize a key role of local
      institutions. 

PMID- 25764505
TI  - Foraging syndromes and trait variation in antlions along a climatic gradient.
AB  - Behavioral syndromes arise when individual behavior is correlated over time
      and/or across environmental contexts, often resulting in inter-population
      behavioral differences. Three main hypotheses have been suggested to explain the
      evolution of behavioral syndromes. The constraint hypothesis suggests that
      behaviors originate from a shared mechanism with a strong genetic or
      physiological basis. In contrast, according to the adaptive hypothesis,
      behavioral syndromes depend on specific selective pressures in each environment,
      and thus should evolve when specific behavioral combinations are advantageous.
      Finally, behavioral syndromes can also arise owing to neutral stochastic
      processes. We tested here for variation in the foraging syndromes of pit-building
      antlions originating from different populations along a climatic gradient.
      Although inter-population variation existed in some traits, foraging syndromes
      were similar across populations, supporting the constraint hypothesis. These
      findings suggest that stabilizing selection, acting on the foraging behavior of
      antlions during their larval phase, outweighs local selection pressures,
      resulting in "constraint syndromes." We also explored behavioral repeatability of
      foraging-related traits within and among habitats (natural, novel and disturbed
      habitats), and detected different levels of repeatability: pit diameter was more
      repeatable than response time to prey, followed by prey exploitation efficiency.
      Behavioral repeatability of the same trait differed according to context,
      suggesting that repeatability is a trait in itself and should not be considered
      identical even when studying the same behavioral trait. 

PMID- 25764506
TI  - Entropic separation of styrene/ethylbenzene mixtures by exploitation of subtle
      differences in molecular configurations in ordered crystalline nanoporous
      adsorbents.
AB  - The separation of styrene/ethylbenzene mixture is of great importance in the
      petrochemical industry. Current technology uses distillation; this separation is
      difficult because of the small, 9 K, difference in the boiling points. An
      alternative separation method uses selective adsorption in nanoporous materials
      such as zeolites and metal-organic frameworks. Here we present a simulation
      screening study for the separation of styrene/ethylbenzene mixture by adsorptive
      means in nanoporous materials near pore saturation conditions. Under these
      conditions, different entropic mechanisms can dictate the separation process.
      Commensurate stacking has the best trade-off between selectivity and saturation
      capacity and offers a geometrical solution to the separation problem. MIL-47 has
      the right channel size and topology for styrene to exhibit commensurate stacking
      offering high capacity and selectivity for styrene over ethylbenzene. Out of all
      the screened structures, MIL-47 was found to be the best candidate for the
      separation of styrene/ethylbenzene mixture. 

PMID- 25764507
TI  - Efficiency analysis of surgical services by combined use of data envelopment
      analysis and gray relational analysis.
AB  - The aim of this study was to determine the efficiency of surgical services
      offered by a public hospital, to rank efficient services and to determine
      important factors on efficiency of services. DEA (to determine efficiency of
      services) and GRA (to rank efficient services and ranking of important variables
      in efficiency) were used in this study. DEA showed that all services were
      observably efficient except Cardiovascular and Plastic surgery. GRA showed that
      the services of Ophthalmology, Otorhinolaryngology (ENT) and Paediatric Surgery
      shared the first three ranks in order of decreasing frequency. Findings obtained
      from GRA, the most important variables in the performances of surgical services
      were found to be the number of patients and healthcare personnel. Findings
      obtained from this study are thought to help inefficient services to attain an
      efficient structure. When the importance of this issue regarding hospitals and
      the government is considered, similarly designed studies should be continually
      updated and revised in line with changing circumstances. When shortcomings in the
      existing literature are taken into account, this could be considered to be a
      pioneer study that will contribute to the literature and promote future studies
      to be conducted on this issue. 

PMID- 25764508
TI  - Combined Cerebral and Renal Near-Infrared Spectroscopy After Congenital Heart
      Surgery.
AB  - The maintenance of an adequate oxygen supply to tissues after congenital heart
      surgery is essential for good outcomes. The objective of this study was to assess
      the usefulness of near-infrared spectroscopy (NIRS) for estimating central venous
      oxygen saturation (ScvO2) using both cerebral and renal measurements, explore its
      relation with cardiac output measurements and check its ability to detect low
      cardiac output. A prospective observational pilot study was conducted in patients
      weighing <10 kg undergoing cardiopulmonary bypass surgery. Spectroscopy probes
      were placed on the forehead and renal area, and serial cardiac output
      measurements were obtained by femoral transpulmonary thermodilution over the
      first 24 h after surgery. In the 15 patients studied, ScvO2 was correlated with
      cerebral (r = 0.58), renal (r = 0.60) and combined (r = 0.71) measurements.
      Likewise, the systolic index was correlated with the NIRS signals: cerebral (r =
      0.60), renal (r = 0.50) and combined (r = 0.66). Statistically significant
      differences were found in the NIRS measures registered in the 29 low cardiac
      output events detected by thermodilution: cerebral: 62 % (59-65) versus 69 % (63
      76); renal: 83 % (70-89) versus 89 % (83-95); and combined 64 % (60-69) versus 72
      % (67-76). In our series, combined cerebral and renal monitoring was correlated
      with central venous oxygen saturation and cardiac output; low cardiac output
      detection associated a different spectroscopy pattern.

PMID- 25764509
TI  - Left Ventricular Dysfunction Following Neonatal Pulmonary Valve Balloon Dilation
      for Pulmonary Atresia or Critical Pulmonary Stenosis.
AB  - Pulmonary valve (PV) balloon dilation (BD) is the primary therapy for infants
      born with critical pulmonary stenosis (PS) or membranous pulmonary atresia with
      intact ventricular septum (PAIVS). We observed left ventricular (LV) dysfunction
      in patients following BD and sought to determine its incidence, clinical course
      and associated risk factors. Clinical, echocardiographic and catheterization data
      for all patients who underwent neonatal (<2 weeks age) PV BD for critical PS or
      PAIVS between January 2000 and February 2014 were retrospectively analyzed (n =
      129). Post-procedure LV dysfunction was defined as ejection fraction (EF) <54 %.
      Median age at PV BD was 1 day. Most (71 %) patients had critical PS. Median PV
      diameter pre-BD was 6.0 mm with PV z-scores -4.1 to 0.9, median LV EF pre-BD was
      58 %. Post-BD LV dysfunction developed in 45 patients (35 %); 15 patients had LV
      EF <=40 %. Median time to normalization of LV EF was 10 days (range 2-72). In
      univariate analysis, diagnosis (critical PS or PAIVS), right ventricle to LV
      pressure ratio pre-BD, acute procedural complication and post-BD inotropic
      support were not associated with post-BD LV dysfunction. In multivariable
      analysis, the predictors of post-procedure LV dysfunction were lower PV z-score
      (OR 1.81, p 0.04), tricuspid regurgitation pre-BD >= moderate (OR 3.73, p 0.008)
      and larger right ventricular apical area (OR 1.99, p 0.04). LV dysfunction post
      neonatal PV BD develops in a significant number of patients (35 %) and can be
      severe, but resolves. The risk of developing LV dysfunction post-PV BD is highest
      in patients with larger right ventricles.

PMID- 25764510
TI  - Static progressive versus dynamic splinting for posttraumatic elbow stiffness: a
      systematic review of 232 patients.
AB  - INTRODUCTION: The elbow is prone to stiffness after trauma. To regain functional
      elbow motion, several conservative and surgical treatment options are available.
      Nonoperative treatment includes physical therapy, intra-articular injections with
      corticosteroids, and a static progressive or dynamic splinting program. The
      objective of this study was to perform a comprehensive review of the literature
      to evaluate the best current evidence for nonoperative treatment options for
      posttraumatic elbow stiffness. METHODS: We performed a search of all studies on
      nonoperative treatment for elbow stiffness in human adults. All articles
      describing nonoperative treatment of elbow stiffness, written in the English,
      German, French or Dutch language, including human adult patients and with the
      functional outcome reported were included in this study. RESULTS: Eight studies
      (including 232 patients) met our eligibility criteria and were included for data
      analysis and pooling. These studies included one randomized controlled trial and
      seven retrospective cohort studies. Static progressive splinting was evaluated in
      160 patients. The average pre-splinting range of motion of all elbows was 72
      degrees , which improved by 36 degrees  after splinting to an average post
      splinting arc of motion of 108 degrees . Dynamic splinting was evaluated in 72
      patients with an average pre-splinting range of motion of 63 degrees . The
      average improvement was 37 degrees  to an average post-splinting arc of motion of
      100 degrees . CONCLUSIONS: Both dynamic orthoses and static progressive splinting
      show good results for the treatment of elbow stiffness, regardless of etiology.
      The choice for one treatment over the other is based on the preference of the
      surgeon and patient. We recommend to continue nonoperative treatment with dynamic
      or static bracing for 12 months or until patients stop making progression in
      range of elbow motion.

PMID- 25764511
TI  - Differential expression patterns of K(+) /Cl(-) cotransporter 2 in neurons within
      the superficial spinal dorsal horn of rats.
AB  - gamma-Aminobutyric acid (GABA)- and glycine-mediated hyperpolarizing inhibition
      is associated with a chloride influx that depends on the inwardly directed
      chloride electrochemical gradient. In neurons, the extrusion of chloride from the
      cytosol primarily depends on the expression of an isoform of potassium-chloride
      cotransporters (KCC2s). KCC2 is crucial in the regulation of the inhibitory tone
      of neural circuits, including pain processing neural assemblies. Thus we
      investigated the cellular distribution of KCC2 in neurons underlying pain
      processing in the superficial spinal dorsal horn of rats by using high-resolution
      immunocytochemical methods. We demonstrated that perikarya and dendrites widely
      expressed KCC2, but axon terminals proved to be negative for KCC2. In single
      ultrathin sections, silver deposits labeling KCC2 molecules showed different
      densities on the surface of dendritic profiles, some of which were negative for
      KCC2. In freeze fracture replicas and tissue sections double stained for the
      beta3-subunit of GABAA receptors and KCC2, GABAA receptors were revealed on
      dendritic segments with high and also with low KCC2 densities. By measuring the
      distances between spots immunoreactive for gephyrin (a scaffolding protein of
      GABAA and glycine receptors) and KCC2 on the surface of neurokinin 1 (NK1)
      receptor-immunoreactive dendrites, we found that gephyrin-immunoreactive spots
      were located at various distances from KCC2 cotransporters; 5.7 % of them were
      recovered in the middle of 4-10-um-long dendritic segments that were free of KCC2
      immunostaining. The variable local densities of KCC2 may result in variable
      postsynaptic potentials evoked by the activation of GABAA and glycine receptors
      along the dendrites of spinal neurons.

PMID- 25764513
TI  - Flexibility of oral cholera vaccine dosing-a randomized controlled trial
      measuring immune responses following alternative vaccination schedules in a
      cholera hyper-endemic zone.
AB  - BACKGROUND: A bivalent killed whole cell oral cholera vaccine has been found to
      be safe and efficacious for five years in the cholera endemic setting of Kolkata,
      India, when given in a two dose schedule, two weeks apart. A randomized
      controlled trial revealed that the immune response was not significantly
      increased following the second dose compared to that after the first dose. We
      aimed to evaluate the impact of an extended four week dosing schedule on
      vibriocidal response. METHODOLOGY/PRINCIPAL FINDINGS: In this double blind
      randomized controlled non-inferiority trial, 356 Indian, non-pregnant residents
      aged 1 year or older were randomized to receive two doses of oral cholera vaccine
      at 14 and 28 day intervals. We compared vibriocidal immune responses between
      these schedules. Among adults, no significant differences were noted when
      comparing the rates of seroconversion for V. cholerae O1 Inaba following two dose
      regimens administered at a 14 day interval (55%) vs the 28 day interval (58%).
      Similarly, no differences in seroconversion were demonstrated in children
      comparing the 14 (80%) and 28 day intervals (77%). Following 14 and 28 day dosing
      intervals, vibriocidal response rates against V. cholerae O1 Ogawa were 45% and
      49% in adults and 73% and 72% in children respectively. Responses were lower for
      V. cholerae O139, but similar between dosing schedules for adults (20%, 20%) and
      children (28%, 20%). CONCLUSIONS/SIGNIFICANCE: Comparable immune responses and
      safety profiles between the two dosing schedules support the option for increased
      flexibility of current OCV dosing. Further operational research using a longer
      dosing regimen will provide answers to improve implementation and delivery of
      cholera vaccination in endemic and epidemic outbreak scenarios.

PMID- 25764512
TI  - Chitin recognition via chitotriosidase promotes pathologic type-2 helper T cell
      responses to cryptococcal infection.
AB  - Pulmonary mycoses are often associated with type-2 helper T (Th2) cell responses.
      However, mechanisms of Th2 cell accumulation are multifactorial and incompletely
      known. To investigate Th2 cell responses to pulmonary fungal infection, we
      developed a peptide-MHCII tetramer to track antigen-specific CD4+ T cells
      produced in response to infection with the fungal pathogen Cryptococcus
      neoformans. We noted massive accruement of pathologic cryptococcal antigen
      specific Th2 cells in the lungs following infection that was coordinated by lung
      resident CD11b+ IRF4-dependent conventional dendritic cells. Other researchers
      have demonstrated that this dendritic cell subset is also capable of priming
      protective Th17 cell responses to another pulmonary fungal infection, Aspergillus
      fumigatus. Thus, higher order detection of specific features of fungal infection
      by these dendritic cells must direct Th2 cell lineage commitment. Since chitin
      containing parasites commonly elicit Th2 responses, we hypothesized that
      recognition of fungal chitin is an important determinant of Th2 cell-mediated
      mycosis. Using C. neoformans mutants or purified chitin, we found that chitin
      abundance impacted Th2 cell accumulation and disease. Importantly, we determined
      Th2 cell induction depended on cleavage of chitin via the mammalian chitinase,
      chitotriosidase, an enzyme that was also prevalent in humans experiencing overt
      cryptococcosis. The data presented herein offers a new perspective on fungal
      disease susceptibility, whereby chitin recognition via chitotriosidase leads to
      the initiation of harmful Th2 cell differentiation by CD11b+ conventional
      dendritic cells in response to pulmonary fungal infection. 

PMID- 25764514
TI  - Inverse association between Bmi-1 and RKIP affecting clinical outcome of gastric
      cancer and revealing the potential molecular mechanisms underlying tumor
      metastasis and chemotherapy resistance.
AB  - BACKGROUND: B-cell-specific Moloney murine leukemia virus integration site 1 (Bmi
      1) and Raf kinase inhibitory protein (RKIP) are involved in cancer metastasis and
      chemotherapeutic resistance, respectively. In this study, we evaluated the
      association between Bmi-1 and RKIP and outcome of gastric cancer through clinical
      data analysis and in vitro experiments. METHODS: Bmi-1 expression and RKIP
      expression were observed in 107 cases of gastric cancer through use of tissue
      microarray technology to identify their correlations with clinicopathological
      parameters, patient survival, and susceptibility to chemotherapy. The correlation
      was confirmed in gastric cancer cell lines, analyzed further by gene
      overexpression and silencing analysis, a cell invasion assay, and a
      chemosensitivity test. RESULTS: Positive expression of Bmi-1 was highly
      correlated with T classification and clinical stage. Diminished or lost
      expression of RKIP was significantly associated with T classification, lymph node
      metastasis, distant metastasis, and clinical stage. Bmi-1 is negatively and RKIP
      is positively related to patient survival. Positive expression of Bmi-1 and
      negative expression of RKIP are associated with poor patient survival and modest
      efficacy of postoperative chemotherapy. A meaningfully inverse association
      between Bmi-1 and RKIP was found in tissue microarray studies, and was verified
      further in gastric cancer cell lines. Moreover, gene overexpression and silencing
      analysis indicated that RKIP might be regulated by Bmi-1. Furthermore, the
      impacts of Bmi-1 on cell invasion and chemotherapy resistance were rescued by
      knockdown of RKIP. CONCLUSIONS: Our study implies that detection of Bmi-1 and
      RKIP is valuable in predicting patient survival and therapeutic response in
      gastric cancer, and the inverse association between Bmi-1 and RKIP reveals the
      potential molecular mechanisms underlying tumor metastasis and chemotherapy
      resistance.

PMID- 25764515
TI  - Expression pattern of inflammatory response genes and their regulatory micrornas
      in bovine oviductal cells in response to lipopolysaccharide: implication for
      early embryonic development.
AB  - In the present study, we used an in vitro model to investigate the response of
      the oviduct with respect to inflammatory mediators and their regulatory microRNAs
      in case of bacterial infection and subsequent association with embryo survival.
      For this, we conducted two experiments. In the first experiment, cultured primary
      bovine oviductal cells (BOEC) were challenged with lipopolysaccharide (LPS) for
      24h and the temporal expression pattern of inflammatory mediators and their
      regulatory microRNAs were measured at 0, 3, 6, 12, 24 and 48h after LPS
      treatment. Intriguingly, the temporal patterns of all miRNAs except miR-21 were
      significantly up-regulated at 6h after LPS treatment. Whereas, we observed
      significant overexpression of pro-inflammatory mediators as tumor necrosis factor
      alpha (TNFalpha) and interleukin-1 beta (IL1beta) after LPS challenge for 24h. On
      the other hand, the expression level of essential elements like oviductal
      glycoprotein 1 (OVGP1) and insulin-like growth factor 2 (IGF2) was significantly
      decreased in challenged groups compared with control. Moreover, miR-155, miR
      146a, miR-223, miR-21, miR-16 and miR-215 have shown a clear suppression in
      challenged group after LPS treatment. In the 2nd experiment there were four
      groups of blastocysts produced, namely embryo+LPS free media, embryo+LPS,
      BOEC+embryo and BOEC+embryo+LPS. The suboptimal oviduct environment due to LPS
      challenge is found to have a significant influence on the expression of
      inflammatory response genes (TNFalpha and CSF1), stress response genes (SOD and
      CAT), mitochondrial activity, reactive oxygen species (ROS) accumulation and
      apoptotic level either in cultured or co-cultured blastocysts. Collectively, LPS
      challenge led to aberrant changes in oviductal transcriptome profile, which could
      lead to a suboptimal environment for embryo development. 

PMID- 25764516
TI  - Minocycline Rescues from Zinc-Induced Nigrostriatal Dopaminergic
      Neurodegeneration: Biochemical and Molecular Interventions.
AB  - Accumulation of zinc (Zn) in dopaminergic neurons is implicated in Parkinson's
      disease (PD), and microglial activation plays a critical role in toxin-induced
      Parkinsonism. Oxidative stress is accused in Zn-induced dopaminergic
      neurodegeneration; however, its connection with microglial activation is still
      not known. This study was undertaken to elucidate the role and underlying
      mechanism of microglial activation in Zn-induced nigrostriatal dopaminergic
      neurodegeneration. Male Wistar rats were treated intraperitoneally with/without
      zinc sulphate (20 mg/kg) in the presence/absence of minocycline (30 mg/kg), a
      microglial activation inhibitor, for 2-12 weeks. While neurobehavioral and
      biochemical indexes of PD and number of dopaminergic neurons were reduced, the
      number of microglial cells was increased in the substantia nigra of the Zn
      exposed animals. Similarly, Zn elevated lipid peroxidation (LPO) and activities
      of superoxide dismutase (SOD) and nicotinamide adenine dinucleotide phosphate
      (NADPH) oxidase; however, catalase activity was reduced. Besides, Zn increased an
      association of NADPH oxidase subunit p67(phox) with membrane, cytochrome c
      release from the mitochondria and cleavage of pro-caspase 3. Zn attenuated the
      expression of tyrosine hydroxylase (TH) and vesicular monoamine transporter-2
      (VMAT-2) while augmented the expression of dopamine transporter (DAT) and heme
      oxygenase-1 (HO-1). Minocycline alleviated Zn-induced behavioural impairments,
      loss of TH-positive neurons, activated microglial cells and biochemical indexes
      and modulated the expression of studied genes/proteins towards normalcy. The
      results demonstrate that minocycline reduces the number of activated microglial
      cells and oxidative stress, which rescue from Zn-induced changes in the
      expression of monoamine transporter and nigrostriatal dopaminergic
      neurodegeneration.

PMID- 25764518
TI  - Is there a relationship between exercise-induced endothelial progenitor cell
      mobilization and cytokine concentrations in patients with premature coronary
      heart disease [corrected].

PMID- 25764519
TI  - Urinary biomarkers of kidney diseases in HIV-infected children.
AB  - A significant number of children infected with the human immunodeficiency virus 1
      (HIV-1) virus all over the world are at risk of developing renal diseases that
      could have a significant impact on their treatment and quality of life. It is
      necessary to identify children undergoing the early stages of these renal
      diseases, as well as the potential renal toxicity that could be caused by
      antiretroviral drugs, in order to prevent the development of cardiovascular
      complications and chronic renal failure. This article describes the most common
      renal diseases seen in HIV-infected children, as well as the value and
      limitations of the clinical markers that are currently being used to monitor
      their renal function and histological damage in a noninvasive manner. In
      addition, we discuss the progress made during the last 10 years in the discovery
      and validation of new renal biomarkers for HIV-infected children and young
      adults. Although significant progress has been made during the early phases of
      the biomarkers discovery, more work remains to be done to validate the new
      biomarkers in a large number of patients. The future looks promising, however,
      the new knowledge needs to be integrated and validated in the context of the
      clinical environment where these children are living. 

PMID- 25764520
TI  - miR-577 inhibits glioblastoma tumor growth via the Wnt signaling pathway.
AB  - microRNAs (miRNAs) are commonly altered in glioblastoma. Publicly available
      algorithms suggest the Wnt pathway is a potential target of miR-577 and the Wnt
      pathway is commonly altered in glioblastoma. Glioblastoma has not been previously
      evaluated for miR-577 expression. Glioblastoma tumors and cell lines were
      evaluated for their expression of miR-577. Cell lines were transfected with miR
      577, miR-577-mutant, or control mimics to evaluate the effect of miR-577
      expression on cell proliferation in vitro and in an animal model. Wnt pathway
      markers were also evaluated for their association with miR-577 expression. miR
      577 expression was decreased in 33 of 40 (82.5%) glioblastoma tumors and 5 of 6
      glioblastoma cell lines. miR-577 expression correlated negatively with cell
      growth and cell viability. miR-577 down-regulation was associated with increased
      expression of the Wnt signaling pathway genes lipoprotein receptor-related
      protein (LRP) 6 (LRP6) and beta-catenin. Western blot analysis confirmed
      decreased expression of the Wnt signaling pathway genes Axin2, c-myc, and cyclin
      D1 in miR-577 transfected cells. miR-577 expression is down-regulated in
      glioblastoma. miR-577 directly targets Wnt signaling pathway components LRP6 and
      beta-catenin. miR-577 suppresses glioblastoma multiforme (GBM) growth by
      regulating the Wnt signaling pathway.

PMID- 25764521
TI  - Comparison between frailty index of deficit accumulation and phenotypic model to
      predict risk of falls: data from the global longitudinal study of osteoporosis in
      women (GLOW) Hamilton cohort.
AB  - OBJECTIVES: To compare the predictive accuracy of the frailty index (FI) of
      deficit accumulation and the phenotypic frailty (PF) model in predicting risks of
      future falls, fractures and death in women aged >=55 years. METHODS: Based on the
      data from the Global Longitudinal Study of Osteoporosis in Women (GLOW) 3-year
      Hamilton cohort (n = 3,985), we compared the predictive accuracy of the FI and PF
      in risks of falls, fractures and death using three strategies: (1) investigated
      the relationship with adverse health outcomes by increasing per one-fifth (i.e.,
      20%) of the FI and PF; (2) trichotomized the FI based on the overlap in the
      density distribution of the FI by the three groups (robust, pre-frail and frail)
      which were defined by the PF; (3) categorized the women according to a predicted
      probability function of falls during the third year of follow-up predicted by the
      FI. Logistic regression models were used for falls and death, while survival
      analyses were conducted for fractures. RESULTS: The FI and PF agreed with each
      other at a good level of consensus (correlation coefficients >= 0.56) in all the
      three strategies. Both the FI and PF approaches predicted adverse health outcomes
      significantly. The FI quantified the risks of future falls, fractures and death
      more precisely than the PF. Both the FI and PF discriminated risks of adverse
      outcomes in multivariable models with acceptable and comparable area under the
      curve (AUCs) for falls (AUCs >= 0.68) and death (AUCs >= 0.79), and c-indices for
      fractures (c-indices >= 0.69) respectively. CONCLUSIONS: The FI is comparable
      with the PF in predicting risks of adverse health outcomes. These findings may
      indicate the flexibility in the choice of frailty model for the elderly in the
      population-based settings.

PMID- 25764522
TI  - Tracing novel hemostatic compounds from heating products of total flavonoids in
      Flos Sophorae by spectrum-effect relationships and column chromatography.
AB  - Flos Sophorae and its processed product have been clinically used to treat
      hemorrhage. In this study, the total ion chromatographic fingerprints of the
      heating products of total flavonoids in Flos Sophorae were established by high
      performance liquid chromatography with tandem mass spectrometry and the
      hemostatic activities were studied by hemostatic screening tests in vivo. The
      spectrum-effect relationships between fingerprints and hemostatic activities were
      investigated using canonical correlation analysis to trace the peaks responsible
      for the hemostatic effects. The predicted active peaks in fingerprints were
      isolated by column chromatography and their structures were identified by NMR
      spectroscopy and mass spectrometry. The hemostatic activities of them were
      verified by platelet aggregation and procoagulation assays in vitro. Canonical
      correlation analysis results showed that peak 8 and peak 11 were correlated most
      closely, thus probably being the main hemostatic compounds. Through column
      chromatography separation, peak 8 (compound I) and peak 11 (compound II) were
      obtained with purities of 95.61 and 93.38%, respectively, and were discovered new
      hemostatic compounds named as huaicarbon A (I) and huaicarbon B (II),
      respectively. This study provides a universal model to trace the active compounds
      of other herbs which have bioactivity enhancement after processing by spectrum
      effect relationships and column chromatography. 

PMID- 25764523
TI  - Effects of Nd:YAG laser irradiation for minimizing edema and pain after sinus
      lift surgery: randomized controlled clinical trial.
AB  - OBJECTIVE: The aim of the present study was to evaluate the effectiveness of
      neodymium-doped yttrium aluminum garnet (Nd:YAG) laser used for low-level laser
      therapy (LLLT) on pain, oral health-related quality of life (OHRQoL), and
      swelling after sinus lift procedure. MATERIALS AND METHODS: Ten healthy patients,
      requiring bilateral direct sinus lift surgery, were included in this prospective,
      randomized study. The treatment sides were randomly assigned to LLLT or control
      groups. The experimental side received 8 J/cm(2) of energy density, a wavelength
      of 1064 nm, for 60 sec, and 0.5 W laser immediately after surgery. Swelling, pain
      perception, and OHRQoL were evaluated at different time intervals. The data were
      analyzed by the one way ANOVA. RESULTS: Evaluations of postoperative pain,
      OHRQoL, and swelling were made. We observed that the swelling and the OHRQoL in
      the Nd:YAG group were significantly improved when compared with the control group
      on the 3rd day after surgery (p<0.05). The pain levels after surgery was almost
      the same for both groups, without statistically significant differences (p>0.05).
      There were no statistically significant differences between groups with regard to
      any of the parameters evaluated on the 7th day. CONCLUSIONS: The results
      demonstrate that the 1064 nm Nd:YAG laser was effective in improving OHRQoL and
      reducing swelling after sinus lift surgery. Within the limitations of this study,
      we concluded that the 1064 nm Nd:YAG laser has beneficial effects on swelling and
      OHRQoL, making it suitable for LLLT.

PMID- 25764524
TI  - Tendon basic science: Development, repair, regeneration, and healing.
AB  - Tendinopathy and tendon rupture are common and disabling musculoskeletal
      conditions. Despite the prevalence of these injuries, a limited number of
      investigators are conducting fundamental, basic science studies focused on
      understanding processes governing tendinopathies and tendon healing. Development
      of effective therapeutics is hindered by the lack of fundamental guiding data on
      the biology of tendon development, signal transduction, mechanotransduction, and
      basic mechanisms underlying tendon pathogenesis and healing. To propel much
      needed progress, the New Frontiers in Tendon Research Conference, co-sponsored by
      NIAMS/NIH, the Orthopaedic Research Society, and the Icahn School of Medicine at
      Mount Sinai, was held to promote exchange of ideas between tendon researchers and
      basic science experts from outside the tendon field. Discussed research areas
      that are underdeveloped and represent major hurdles to the progress of the field
      will be presented in this review. To address some of these outstanding questions,
      conference discussions and breakout sessions focused on six topic areas (Cell
      Biology and Mechanics, Functional Extracellular Matrix, Development, Mechano
      biology, Scarless Healing, and Mechanisms of Injury and Repair), which are
      reviewed in this special issue and briefly presented in this review. Review
      articles in this special issue summarize the progress in the field and identify
      essential new research directions.

PMID- 25764525
TI  - Lengthening temporalis myoplasty for facial paralysis reanimation: an objective
      analysis of each surgical step.
AB  - IMPORTANCE: Lengthening temporalis myoplasty is a dynamic procedure used to
      reanimate the middle third of the paralyzed face. Since its original description,
      it has been progressively modified over the years, with a reduction in the number
      of surgical steps. However, these modifications can decrease lengthening needed
      for the tendon to reach the oral commissure and upper lip without tension or
      overcorrection. OBJECTIVES: To evaluate the maximal lengthening of the temporalis
      tendon that is possible with this technique and to assess the contribution of
      each surgical step to total lengthening. DESIGN, SETTING, AND PARTICIPANTS:
      Cadaveric dissection study from September 16 to 23, 2013, at a tertiary referral
      center using 10 cadaveric hemifaces. MAIN OUTCOMES AND MEASURES: Surgical
      exposure was obtained using coronal and melolabial incisions. The original
      surgical technique was broken down into 7 steps. Measurement of temporalis tendon
      lengthening relative to a fixed point was performed by a single surgeon after
      each surgical step using a millimeter ruler. RESULTS: Each surgical step resulted
      in progressive temporalis tendon lengthening for a median maximal total
      lengthening of 43.5 mm. The steps that contributed most to this lengthening were
      coronoidotomy and intraoral temporalis tendon dissection (median, 12.0 mm),
      incision of temporalis fascia insertion over the orbital rim (median, 6.5 mm),
      and zygomatic osteotomy with dissection of masseteric fibers (median, 11.5 mm),
      which represent the first and last 2 steps of the procedure, respectively.
      CONCLUSIONS AND RELEVANCE: Modifications of lengthening temporalis myoplasty must
      be considered with caution because the maximal lengthening potential can be
      obtained only when performing all 7 surgical steps. These modifications must be
      chosen appropriately based on the lengthening required for the temporalis tendon
      to reach the oral commissure and upper lip without tension or overcorrection.
      LEVEL OF EVIDENCE: NA.

PMID- 25764526
TI  - Can we achieve an 80% screening rate for colorectal cancer by 2018 in the United
      States?

PMID- 25764527
TI  - Enhancement of volatile fatty acids production from rice straw via anaerobic
      digestion with chemical pretreatment.
AB  - Rice straw is one of the most abundant renewable biomass sources and was selected
      as the feedstock for the production of volatile fatty acids (VFAs) from which
      microbial biodiesel can be produced. Two kinds of chemical pretreatments
      involving nitric acid and sodium hydroxide were investigated at 150  degrees C
      with 20 min of reaction time. The nitric acid pretreatment generated the most
      hemicellulose hydrolyzate, while significant reduction of the lignin occurred
      with sodium hydroxide pretreatment. Anaerobic digestion of 20 g/L rice straw
      yielded 6.00 and 7.09 g VFAs/L with 0.5% HNO3 and 2% NaOH, respectively. The VFAs
      yield with 2% NaOH was 0.35 g/g.

PMID- 25764528
TI  - Invasive dreissenid mussels and benthic algae in Lake Michigan: characterizing
      effects on sediment bacterial communities.
AB  - Dreissenid mussels have invaded the Laurentian Great Lakes causing dramatic
      changes to benthic-pelagic interactions. Despite research on food web impacts,
      there is limited data on mussel effects on benthic bacterial communities. This
      study examined effects of dreissenid mussels and benthic algae on sediment
      bacterial community composition and diversity. Triplicate experimental sediment
      plus lake water microcosms were used and either mussels, benthic algae or both
      were added. Changes in water nutrient chemistry and sediment bacterial
      communities were monitored using 16S rRNA amplicon sequencing, over 21 days. When
      mussels were present, nitrate and soluble reactive P increased significantly as
      the dominant N and P forms. Bacterial diversity increased in all microcosms,
      although bacterial community composition was distinct between treatment. Higher
      nitrate in mussel microcosms was accompanied by increases in nitrifying taxa
      (Nitrospira, Nitrosomonas), which are important in oxidizing mussel-excreted
      ammonium. Microcosms with algal additions showed increases in bacterial taxa
      capable of degrading algal cellulose, and Pelagibacter (SAR11) disappeared from
      all but control microcosms. This study suggests that bacterial communities in
      lake sediments respond to mussels and algae. Functional analysis of bacterial
      communities provides insights into changes in microbially mediated benthic
      nutrient transformations associated with invasive dreissenid mussels and benthic
      algae in lake ecosystems. 

PMID- 25764529
TI  - Microbial community composition and functions are resilient to metal pollution
      along two forest soil gradients.
AB  - Despite the global importance of forests, it is virtually unknown how their soil
      microbial communities adapt at the phylogenetic and functional level to long-term
      metal pollution. Studying 12 sites located along two distinct gradients of metal
      pollution in Southern Poland revealed that functional potential and diversity
      (assessed using GeoChip 4.2) were highly similar across the gradients despite
      drastically diverging metal contamination levels. Metal pollution level did,
      however, significantly impact bacterial community structure (as shown by MiSeq
      Illumina sequencing of 16S rRNA genes), but not bacterial taxon richness and
      community composition. Metal pollution caused changes in the relative abundance
      of specific bacterial taxa, including Acidobacteria, Actinobacteria,
      Bacteroidetes, Chloroflexi, Firmicutes, Planctomycetes and Proteobacteria. Also,
      a group of metal-resistance genes showed significant correlations with metal
      concentrations in soil. Our study showed that microbial communities are resilient
      to metal pollution; despite differences in community structure, no clear impact
      of metal pollution levels on overall functional diversity was observed. While
      screens of phylogenetic marker genes, such as 16S rRNA genes, provide only
      limited insight into resilience mechanisms, analysis of specific functional
      genes, e.g. involved in metal resistance, appears to be a more promising
      strategy. 

PMID- 25764530
TI  - Distinct composition signatures of archaeal and bacterial phylotypes in the Wanda
      Glacier forefield, Antarctic Peninsula.
AB  - Several studies have shown that microbial communities in Antarctic environments
      are highly diverse. However, considering that the Antarctic Peninsula is among
      the regions with the fastest warming rates, and that regional climate change has
      been linked to an increase in the mean rate of glacier retreat, the microbial
      diversity in Antarctic soil is still poorly understood. In this study, we
      analysed more than 40 000 sequences of the V5-V6 hypervariable region of the 16S
      rRNA gene obtained by 454 pyrosequencing from four soil samples from the Wanda
      Glacier forefield, King George Island, Antarctic Peninsula. Phylotype diversity
      and richness were surprisingly high, and taxonomic assignment of sequences
      revealed that communities are dominated by Proteobacteria, Bacteroidetes and
      Euryarchaeota, with a high frequency of archaeal and bacterial phylotypes
      unclassified at the genus level and without cultured representative strains,
      representing a distinct microbial community signature. Several phylotypes were
      related to marine microorganisms, indicating the importance of the marine
      environment as a source of colonizers for this recently deglaciated environment.
      Finally, dominant phylotypes were related to different microorganisms possessing
      a large array of metabolic strategies, indicating that early successional
      communities in Antarctic glacier forefield can be also functionally diverse.

PMID- 25764531
TI  - Bacterial communities associated with four ctenophore genera from the German
      Bight (North Sea).
AB  - Intense research has been conducted on jellyfish and ctenophores in recent years.
      They are increasingly recognized as key elements in the marine ecosystem that
      serve as critical indicators and drivers of ecosystem performance and change.
      However, the bacterial community associated with ctenophores is still poorly
      investigated. Based on automated ribosomal intergenic spacer analysis (ARISA) and
      16S ribosomal RNA gene amplicon pyrosequencing, we investigated bacterial
      communities associated with the frequently occurring ctenophore species
      Mnemiopsis leidyi, Beroe sp., Bolinopsis infundibulum and Pleurobrachia pileus at
      Helgoland Roads in the German Bight (North Sea). We observed significant
      differences between the associated bacterial communities of the different
      ctenophore species based on ARISA patterns. With respect to bacterial taxa, all
      ctenophore species were dominated by Proteobacteria as revealed by
      pyrosequencing. Mnemiopsis leidyi and P. pileus mainly harboured
      Gammaproteobacteria, with Marinomonas as the dominant phylotype of M. leidyi. By
      contrast, Pseudoalteromonas and Psychrobacter were the most abundant
      Gammaproteobacteria in P. pileus. Beroe sp. was mainly dominated by
      Alphaproteobacteria, particularly by the genus Thalassospira. For B.
      infundibulum, the bacterial community was composed of Alphaproteobacteria and
      Gammaproteobacteria in equal parts, which consisted of the genera Thalassospira
      and Marinomonas. In addition, the bacterial communities associated with M. leidyi
      display a clear variation over time that needs further investigation. Our results
      indicate that the bacterial communities associated with ctenophores are highly
      species- specific. 

PMID- 25764532
TI  - Adaptation of soil microbial community structure and function to chronic metal
      contamination at an abandoned Pb-Zn mine.
AB  - Toxicity of metals released from mine tailings may cause severe damage to
      ecosystems. A diversity of microorganisms, however, have successfully adapted to
      such sites. In this study, our objective was to advance the understanding of the
      indigenous microbial communities of mining-impacted soils. To this end, a
      metatranscriptomic approach was used to study a heavily metal-contaminated site
      along a metal concentration gradient (up to 3220 000 and 97 000 mg kg(-1) of Cd,
      Pb and Zn, respectively) resulting from previous mining. Metal concentration,
      soil pH and amount of clay were the most important factors determining the
      structure of soil microbial communities. Interestingly, evenness of the microbial
      communities, but not its richness, increased with contamination level. Taxa with
      high metabolic plasticity like Ktedonobacteria and Chloroflexi were found with
      higher relative abundance in more contaminated samples. However, several taxa
      belonging to the phyla Actinobacteria and Acidobacteria followed opposite trends
      in relation to metal pollution. Besides, functional transcripts related to
      transposition or transfer of genetic material and membrane transport, potentially
      involved in metal resistance mechanisms, had a higher expression in more
      contaminated samples. Our results provide an insight into microbial communities
      in long-term metal-contaminated environments and how they contrast to nearby
      sites with lower contamination. 

PMID- 25764533
TI  - Long-term consequences of disturbances on reproductive strategies of the rare
      epiphytic lichen Lobaria pulmonaria: clonality a gift and a curse.
AB  - The effect of disturbance on symbiotic organisms such as lichens is particularly
      severe. In case of heterothallic lichen-forming fungi, disturbances may lead to
      unbalanced gene frequency and patchy distribution of mating types, thus
      inhibiting sexual reproduction and imposing clonality. The impact of disturbance
      on reproductive strategies and genetic diversity of clonal systems has so far
      received little attention. To infer the effects of disturbances on mating-type
      allele frequencies and population structure, we selected three populations in the
      Parc Jurassien Vaudois (Switzerland), which were affected by uneven-aged
      forestry, intensive logging and fire, respectively. We used microsatellite
      markers to infer genetic diversity, allelic richness and clonal diversity of the
      epiphytic lichen Lobaria pulmonaria and used L. pulmonaria-specific MAT1-1 and
      MAT1-2 markers to analyse the frequency and distribution of mating types of 889
      individuals. Our study shows that stand-replacing disturbances affect the mating
      type frequency and distribution, thus compromising the potential for sexual
      reproduction. The fire-disturbed area had a significantly lower genetic and
      genotypic diversity and a higher clonality. Furthermore, the majority of
      compatible mating pairs in this area were beyond the effective vegetative
      dispersal range of the species. We conclude that stand-replacing disturbances
      lead to lower chances of sex and symbiont reshuffling and thus have long-lasting
      negative consequences on the reproductive strategies and adaptive potential of
      epiphytic lichen symbioses. 

PMID- 25764534
TI  - Parental material and cultivation determine soil bacterial community structure
      and fertility.
AB  - Microbes are the key components of the soil environment, playing important roles
      during soil development. Soil parent material provides the foundation elements
      that comprise the basic nutritional environment for the development of microbial
      community. After 30 years artificial maturation of cultivation, the soil
      developments of three different parental materials were evaluated and bacterial
      community compositions were investigated using the high-throughput sequencing
      approach. Thirty years of cultivation increased the soil fertility and soil
      microbial biomass, richness and diversity, greatly changed the soil bacterial
      communities, the proportion of phylum Actinobacteria decreased significantly,
      while the relative abundances of the phyla Acidobacteria, Chloroflexi,
      Gemmatimonadetes, Armatimonadetes and Nitrospira were significantly increased.
      Soil bacterial communities of parental materials were separated with the
      cultivated ones, and comparisons of different soil types, granite soil and
      quaternary red clay soil were similar and different with purple sandy shale soil
      in both parental materials and cultivated treatments. Bacterial community
      variations in the three soil types were affected by different factors, and their
      alteration patterns in the soil development also varied with soil type. Soil
      properties (except total potassium) had a significant effect on the soil
      bacterial communities in all three soil types and a close relationship with
      abundant bacterial phyla. The amounts of nitrogen-fixing bacteria as well as the
      abundances of the nifH gene in all cultivated soils were higher than those in the
      parental materials; Burkholderia and Rhizobacte were enriched significantly with
      long-term cultivation. The results suggested that crop system would not deplete
      the nutrients of soil parental materials in early stage of soil maturation,
      instead it increased soil fertility and changed bacterial community, specially
      enriched the nitrogen-fixing bacteria to accumulate nitrogen during soil
      development. 

PMID- 25764535
TI  - Sea urchin larvae decipher the epiphytic bacterial community composition when
      selecting sites for attachment and metamorphosis.
AB  - Most marine invertebrates have dispersive larvae and relatively immobile adults.
      These developmental stages are linked by a settlement event, which is often
      mediated by specific cues in bacterial biofilms. While larvae distinguish between
      biofilms from different environments, it remains unknown if they receive
      information from all, only a few or even just a single bacterial species in
      natural biofilms. Here we asked how specific is larval settlement to the
      bacterial community structure and/or taxonomically distinguishable groups of
      bacteria in epiphytic marine biofilms? We used novel multivariate statistical
      approaches to investigate if larval settlement of two sea urchins correlated with
      the microbial community composition. Larval settlement of Heliocidaris
      erythrogramma revealed a strong correlation with the community composition,
      highlighted by canonical analysis of principle components, a constrained
      ordination technique. Using this technique, the importance of operational
      taxonomic units (OTUs) within communities relative to larval settlement was
      investigated. Larval settlement not only correlated, both positively and
      negatively, with the epiphytic bacterial community composition but also with the
      relative abundance of few OTUs within these communities. In contrast, no such
      correlation was observed for the other urchin, Holopneustes purpurascens, whose
      larvae likely respond to bacterial biofilms in a more general way and
      specifically respond to a defined settlement cue of algal origin. 

PMID- 25764537
TI  - Plant assemblage composition and soil P concentration differentially affect
      communities of AM and total fungi in a semi-arid grassland.
AB  - Adding inorganic P- and N-fixing legumes to semi-arid grasslands can increase
      forage yield, but soil nutrient concentrations and plant cover may also interact
      to modify soil fungal populations, impacting short- and long-term forage
      production. We tested the effect of plant assemblage (seven native grasses, seven
      native grasses + the domesticated N-fixing legume Medicago sativa, seven native
      grasses + the native N-fixing legume Dalea purpurea or the introduced grass
      Bromus biebersteinii + M. sativa) and soil P concentration (addition of 0 or 200
      P2O5 kg ha(-1) at sowing) on the diversity and community structure of arbuscular
      mycorrhizal (AM) fungi and total fungi over two consecutive years, using 454
      pyrosequencing of 18S rDNA and ITS amplicons. Treatment effects were stronger in
      the wet year (2008) than the dry year (2009). The presence of an N-fixing legume
      with native grasses generally increased AM fungal diversity, while the
      interaction between soil P concentration and plant assemblage modified total
      fungal community structure in 2008. Excluding interannual variations, which are
      likely driven by moisture and plant productivity, AM fungal communities in semi
      arid grasslands appear to be primarily affected by plant assemblage composition,
      while the composition of other fungi is more closely linked to soil P. 

PMID- 25764538
TI  - Biogeography and ecology of the rare and abundant microbial lineages in deep-sea
      hydrothermal vents.
AB  - Environmental gradients generate countless ecological niches in deep-sea
      hydrothermal vent systems, which foster diverse microbial communities. The
      majority of distinct microbial lineages in these communities occur in very low
      abundance. However, the ecological role and distribution of rare and abundant
      lineages, particularly in deep, hot subsurface environments, remain unclear.
      Here, we use 16S rRNA tag sequencing to describe biogeographic patterning and
      microbial community structure of both rare and abundant archaea and bacteria in
      hydrothermal vent systems. We show that while rare archaeal lineages and almost
      all bacterial lineages displayed geographically restricted community structuring
      patterns, the abundant lineages of archaeal communities displayed a much more
      cosmopolitan distribution. Finally, analysis of one high-volume, high-temperature
      fluid sample representative of the deep hot biosphere described a unique
      microbial community that differed from microbial populations in diffuse flow
      fluid or sulfide samples, yet the rare thermophilic archaeal groups showed
      similarities to those that occur in sulfides. These results suggest that while
      most archaeal and bacterial lineages in vents are rare and display a highly
      regional distribution, a small percentage of lineages, particularly within the
      archaeal domain, are successful at widespread dispersal and colonization. 

PMID- 25764536
TI  - Microbial community composition and diversity in Caspian Sea sediments.
AB  - The Caspian Sea is heavily polluted due to industrial and agricultural effluents
      as well as extraction of oil and gas reserves. Microbial communities can
      influence the fate of contaminants and nutrients. However, insight into the
      microbial ecology of the Caspian Sea significantly lags behind other marine
      systems. Here we describe microbial biomass, diversity and composition in
      sediments collected from three sampling stations in the Caspian Sea. Illumina
      sequencing of 16S rRNA genes revealed the presence of a number of known bacterial
      and archaeal heterotrophs suggesting that organic carbon is a primary factor
      shaping microbial communities. Surface sediments collected from bottom waters
      with low oxygen levels were dominated by Gammaproteobacteria while surface
      sediments collected from bottom waters under hypoxic conditions were dominated by
      Deltaproteobacteria, specifically sulfate-reducing bacteria. Thaumarchaeota was
      dominant across all surface sediments indicating that nitrogen cycling in this
      system is strongly influenced by ammonia-oxidizing archaea. This study provides a
      baseline assessment that may serve as a point of reference as this system changes
      or as the efficacy of new remediation efforts are implemented. 

PMID- 25764539
TI  - Spatial variations in the microbial community structure and diversity of the
      human foot is associated with the production of odorous volatiles.
AB  - The human foot provides an ideal environment for the colonization and growth of
      bacteria and subsequently is a body site associated with the liberation of odour.
      This study aimed to enumerate and spatially map bacterial populations' resident
      across the foot to understand any association with odour production. Culture
      based analysis confirmed that Staphylococci were present in higher numbers than
      aerobic corynebacteria and Gram-positive aerobic cocci, with all species being
      present at much higher levels on the plantar sites compared to dorsal sites.
      Microbiomic analysis supported these findings demonstrating that Staphylococcus
      spp. were dominant across different foot sites and comprised almost the entire
      bacterial population on the plantar surface. The levels of volatile fatty acids,
      including the key foot odour compound isovaleric acid, that contribute to foot
      odour were significantly increased at the plantar skin site compared to the
      dorsal surface. The fact that isovaleric acid was not detected on the dorsal
      surface but was present on the plantar surface is probably attributable to the
      high numbers of Staphylococcus spp. residing at this site. Variations in the
      spatial distribution of these microbes appear to be responsible for the localized
      production of odour across the foot. 

PMID- 25764540
TI  - Editorial: from the chief editor.

PMID- 25764541
TI  - Altered gut microbial energy and metabolism in children with non-alcoholic fatty
      liver disease.
AB  - Obesity is becoming the new pediatric epidemic. Non-alcoholic fatty liver disease
      (NAFLD) is frequently associated with obesity and has become the most common
      cause of pediatric liver disease. The gut microbiome is the major metabolic organ
      and determines how calories are processed, serving as a caloric gate and
      contributing towards the pathogenesis of NAFLD. The goal of this study is to
      examine gut microbial profiles in children with NAFLD using phylogenetic,
      metabolomic, metagenomic and proteomic approaches. Fecal samples were obtained
      from obese children with or without NAFLD and healthy lean children. Stool
      specimens were subjected to 16S rRNA gene microarray, shotgun sequencing, mass
      spectroscopy for proteomics and NMR spectroscopy for metabolite analysis.
      Children with NAFLD had more abundant Gammaproteobacteria and Prevotella and
      significantly higher levels of ethanol, with differential effects on short chain
      fatty acids. This group also had increased genomic and protein abundance for
      energy production with a reduction in carbohydrate and amino acid metabolism and
      urea cycle and urea transport systems. The metaproteome and metagenome showed
      similar findings. The gut microbiome in pediatric NAFLD is distinct from lean
      healthy children with more alcohol production and pathways allocated to energy
      metabolism over carbohydrate and amino acid metabolism, which would contribute to
      development of disease. 

PMID- 25764543
TI  - Arthropod-Spiroplasma relationship in the genomic era.
AB  - The genus Spiroplasma comprises wall-less, low-GC bacteria that establish
      pathogenic, mutualistic and commensal symbiotic associations with arthropods and
      plants. This review focuses on the symbiotic relationships between Spiroplasma
      bacteria and arthropod hosts in the context of the available genomic sequences.
      Spiroplasma genomes are reduced and some contain highly repetitive plectrovirus
      related sequences. Spiroplasma's diversity in viral invasion susceptibility,
      virulence factors, substrate utilization, genome dynamics and symbiotic
      associations with arthropods make this bacterial genus a biological model that
      provides insights about the evolutionary traits that shape bacterial symbiotic
      relationships with eukaryotes. 

PMID- 25764542
TI  - Detection and diversity of copper containing nitrite reductase genes (nirK) in
      prokaryotic and fungal communities of agricultural soils.
AB  - Microorganisms are capable of producing N2 and N2O gases as the end products of
      denitrification. Copper-containing nitrite reductase (NirK), a key enzyme in the
      microbial N-cycle, has been found in bacteria, archaea and fungi. This study
      seeks to assess the diversity of nirK genes in the prokaryotic and fungal
      communities of agricultural soils in the United States. New primers targeting the
      nirK genes in fungi were developed, while nirK genes in archaea and bacteria were
      detected using previously published methods. The new primers were able to detect
      fungal nirK genes as well as bacterial nirK genes from a group that could not be
      observed with previously published primers. Based on the sequence analyses from
      three different primer sets, five clades of nirK genes were identified, which
      were associated with soil archaea, ammonium-oxidizing bacteria, denitrifying
      bacteria and fungi. The diversity of nirK genes in the two denitrifying bacteria
      clades was higher than the diversity found in other clades. Using a newly
      designed primer set, this study showed the detection of fungal nirK genes from
      environmental samples. The newly designed PCR primers in this study enhance the
      ability to detect the diversity of nirK-encoding microorganisms in soils. 

PMID- 25764544
TI  - Characterization of a lytic cyanophage that infects the bloom-forming
      cyanobacterium Aphanizomenon flos-aquae.
AB  - Vb-AphaS-CL131 is a novel cyanosiphovirus that infects harmful Aphanizomenon flos
      aquae. This cyanophage has an isometric head, 97 nm in diameter and a long,
      flexible non-contractile tail, 361 nm long. With a genome size of ~120 kb, it is
      the second largest cyanosiphovirus isolated to date. The latent period was
      estimated to be ~36 h and a single infected cell produces, on average, 218
      infectious cyanophages. Cyanophage infection significantly suppresses host
      biomass production and alters population phenotype.

PMID- 25764545
TI  - Climate-induced die-off affects plant-soil-microbe ecological relationship and
      functioning.
AB  - This study reports the relationship between the diversity and functioning of
      fungal and bacterial soil communities with vegetation in Mediterranean woodland
      that experienced severe die-off after a drought episode. Terminal restriction
      fragment length polymorfism (TRFLP) was used to describe microbial community
      structure and diversity five years after the episode in different habitats
      (Juniperus woodland, shrubland, grassland), when the vegetation had not yet
      recovered. Vegetation diversity was positively related to TRF bacterial richness
      under unaffected canopies and was higher in diverse grassland. Fungal TRF
      richness correlated with vegetation type, being greater in Juniperus woodland.
      Microbial respiration increased in grassland, whereas microbial biomass,
      estimated from soil substrate-induced respiration (SIR), decreased with bacterial
      diversity. Die-off increased bacterial richness and changed bacterial
      composition, particularly in Juniperus woodland, where herbaceous species
      increased, while fungal diversity was reduced in Juniperus woodland. Die-off
      increased microbial respiration rates. The impact on vegetation from extreme
      weather episodes spread to microbial communities by modifying vegetation
      composition and litter quantity and quality, particularly as a result of the
      increase in herbaceous species. Our results suggest that climate-induced die-off
      triggers significant cascade effects on soil microbial communities, which may in
      turn further influence ecosystem C dynamics. 

PMID- 25764546
TI  - Rapid spread of the defensive endosymbiont Spiroplasma in Drosophila hydei under
      high parasitoid wasp pressure.
AB  - Maternally transmitted endosymbionts of insects are ubiquitous in nature and play
      diverse roles in the ecology and evolution of their hosts. To persist in host
      lineages, many symbionts manipulate host reproduction to their advantage (e.g.
      cytoplasmic incompatibility and male-killing), or confer fitness benefits to
      their hosts (e.g. metabolic provisioning and defense against natural enemies).
      Recent studies suggest that strains of the bacterial genus Spiroplasma protect
      their host (flies in the genus Drosophila) against parasitoid attack. The
      Spiroplasma-conferred protection is partial and flies surviving a wasp attack
      have reduced adult longevity and fecundity. Therefore, it is unclear whether
      protection against wasps alone can counter Spiroplasma loss by imperfect maternal
      transmission and any possible fitness costs to harboring Spiroplasma. To address
      this question, we conducted a population cage study comparing Spiroplasma
      frequencies over time (host generations) under conditions of high wasp pressure
      and no wasp pressure. A dramatic increase of Spiroplasma prevalence was observed
      under high wasp pressure. In contrast, Spiroplasma prevalence in the absence of
      wasps did not change significantly over time; a pattern consistent with random
      drift. Thus, the defensive mechanism may contribute to the high prevalence of
      Spiroplasma in host populations despite imperfect vertical transmission. 

PMID- 25764547
TI  - Impact of plant harvest management on function and community structure of
      nitrifiers and denitrifiers in a constructed wetland.
AB  - Plant harvest is one of the most important management practices in constructed
      wetlands. In this study, we evaluated the impact of harvesting Phragmites
      australis (Cav.) Trin. ex Steudel on the activity and community structure of
      nitrifiers and denitrifiers in a free-water surface constructed wetland. The
      nitrifiers were targeted using bacterial and archaeal-amoA that encode ammonia
      monooxygenase, and the denitrifiers were targeted using nirK and nirS that encode
      the nitrite reductase. The community structures were evaluated using denaturing
      gradient gel electrophoresis. The potential nitrification and nitrate reduction
      rates were shown to be significantly higher in the harvested plant rhizosphere
      than in a non-harvested control plot. The potential nitrification rate positively
      correlated with the potential nitrate reduction rate and influenced the community
      structure of nirK. In addition, plant canopy developed differently after harvest
      and simultaneously changed the microclimate beneath the plant community. These
      results suggest that plant harvest management could change subsequent plant
      development and associated microenvironments, thereby affecting the function and
      community structure of nitrifiers and denitrifiers. Our study highlights the
      importance of plant harvest management within constructed wetlands to regulate
      the functions of nitrification and denitrification. 

PMID- 25764548
TI  - Bacterial motion in narrow capillaries.
AB  - Motile bacteria often have to pass through small tortuous pores in soil or tissue
      of higher organisms. However, their motion in this prevalent type of niche is not
      fully understood. Here, we modeled it with narrow glass capillaries and
      identified a critical radius (Rc) for bacterial motion. Near the surface of
      capillaries narrower than that, the swimming trajectories are helices. In larger
      capillaries, they swim in distorted circles. Under non-slip condition, the
      peritrichous Escherichia coli swam in left-handed helices with an Rc of ~10 MUm
      near glass surface. However, slipping could occur in the fast monotrichous
      Pseudomonas fluorescens, when a speed threshold was exceeded, and thus both left
      handed and right-handed helices were executed in glass capillaries. In the
      natural non-cylindrical pores, the near-surface trajectories would be spirals and
      twisted loops. Engaging in such motions reduces the bacterial migration rate.
      With a given pore size, the run length and the tumbling angle of the bacterium
      determine the probability and duration of their near-surface motion. Shear flow
      and chemotaxis potentially enhance it. Based on this observation, the puzzling
      previous observations on bacterial migration in porous environments can be
      interpreted.

PMID- 25764549
TI  - Drying effects on archaeal community composition and methanogenesis in bromeliad
      tanks.
AB  - Tank bromeliads are highly abundant epiphytes in neotropical forests and form a
      unique canopy wetland ecosystem which is involved in the global methane cycle.
      Although the tropical climate is characterized by high annual precipitation, the
      plants can face periods of restricted water. Thus, we hypothesized that water is
      an important controller of the archaeal community composition and the pathway of
      methane formation in tank bromeliads. Greenhouse experiments were established to
      investigate the resident and active archaeal community targeting the 16S rDNA and
      16S rRNA in the tank slurry of bromeliads at three different moisture levels.
      Archaeal community composition and abundance were determined using terminal
      restriction fragment length polymorphism and quantitative PCR. Release of methane
      and its stable carbon isotopic signature were determined in a further incubation
      experiment under two moisture levels. The relative abundance of aceticlastic
      Methanosaetaceae increased up to 34% and that of hydrogenotrophic
      Methanobacteriales decreased by more than half with decreasing moisture.
      Furthermore, at low moisture levels, methane production was up to 100-fold lower
      (<=0.1-1.1 nmol gdw(-1) d(-1)) than under high moisture levels (10-15 nmol gdw(
      1) d(-1)). The rapid response of the archaeal community indicates that the
      pathway of methane formation in bromeliad tanks may indeed be strongly
      susceptible to periods of drought in neotropical forest canopies. 

PMID- 25764550
TI  - Ice formation and growth shape bacterial community structure in Baltic Sea drift
      ice.
AB  - Drift ice, open water and under-ice water bacterial communities covering several
      developmental stages from open water to thick ice were studied in the northern
      Baltic Sea. The bacterial communities were assessed with 16S rRNA gene terminal
      restriction fragment length polymorphism and cloning, together with bacterial
      abundance and production measurements. In the early stages, open water and
      pancake ice were dominated by Alphaproteobacteria and Actinobacteria, which are
      common bacterial groups in Baltic Sea wintertime surface waters. The pancake ice
      bacterial communities were similar to the open-water communities, suggesting that
      the parent water determines the sea-ice bacterial community in the early stages
      of sea-ice formation. In consolidated young and thick ice, the bacterial
      communities were significantly different from water bacterial communities as well
      as from each other, indicating community development in Baltic Sea drift ice
      along with ice-type changes. The thick ice was dominated by typical sea-ice
      genera from classes Flavobacteria and Gammaproteobacteria, similar to those in
      polar sea-ice bacterial communities. Since the thick ice bacterial community was
      remarkably different from that of the parent seawater, results indicate that
      thick ice bacterial communities were recruited from the rarer members of the
      seawater bacterial community. 

PMID- 25764551
TI  - Ammonia-oxidizing archaea respond positively to inorganic nitrogen addition in
      desert soils.
AB  - In soils, nitrogen (N) addition typically enhances ammonia oxidation (AO) rates
      and increases the population density of ammonia-oxidizing bacteria (AOB), but not
      that of ammonia-oxidizing archaea (AOA). We asked if long-term inorganic N
      addition also has similar consequences in arid land soils, an understudied yet
      spatially ubiquitous ecosystem type. Using Sonoran Desert top soils from between
      and under shrubs within a long-term N-enrichment experiment, we determined
      community concentration-response kinetics of AO and measured the total and
      relative abundance of AOA and AOB based on amoA gene abundance. As expected, N
      addition increased maximum AO rates and the abundance of bacterial amoA genes
      compared to the controls. Surprisingly, N addition also increased the abundance
      of archaeal amoA genes. We did not detect any major effects of N addition on
      ammonia-oxidizing community composition. The ammonia-oxidizing communities in
      these desert soils were dominated by AOA as expected (78% of amoA gene copies
      were related to Nitrososphaera), but contained unusually high contributions of
      Nitrosomonas (18%) and unusually low numbers of Nitrosospira (2%). This study
      highlights unique traits of ammonia oxidizers in arid lands, which should be
      considered globally in predictions of AO responses to changes in N availability. 

PMID- 25764552
TI  - Symbiotic diversity, specificity and distribution of rhizobia in native legumes
      of the Core Cape Subregion (South Africa).
AB  - Rhizobial diversity and host preferences were assessed in 65 native Fynbos
      legumes of the papilionoid legume tribes Astragaleae, Crotalarieae, Genisteae,
      Indigofereae, Millettieae, Phaseoleae, Podalyrieae, Psoraleeae and Sesbanieae.
      Sequence analyses of chromosomal 16S rRNA, recA, atpD and symbiosis-related nodA,
      nifH genes in parallel with immunogold labelling assays identified the symbionts
      as alpha- (Azorhizobium, Bradyrhizobium, Ensifer, Mesorhizobium and Rhizobium)
      and beta-rhizobial (Burkholderia) lineages with the majority placed in the genera
      Mesorhizobium and Burkholderia showing a wide range of host interactions. Despite
      a degree of symbiotic promiscuity in the tribes Crotalarieae and Indigofereae
      nodulating with both alpha- and beta-rhizobia, Mesorhizobium symbionts appeared
      to exhibit a general host preference for the tribe Psoraleeae, whereas
      Burkholderia prevailed in the Podalyrieae. Although host genotype was the main
      factor determining rhizobial diversity, ecological factors such as soil acidity
      and site elevation were positively correlated with genetic variation within
      Mesorhizobium and Burkholderia, respectively, indicating an interplay of host and
      environmental factors on the distribution of Fynbos rhizobia. 

PMID- 25764554
TI  - Physicochemical conditions, metabolites and community structure of the bacterial
      microbiota in the gut of wood-feeding cockroaches (Blaberidae: Panesthiinae).
AB  - While the gut microbiota of termites and its role in symbiotic digestion have
      been studied for decades, little is known about the bacteria colonizing the
      intestinal tract of the distantly related wood-feeding cockroaches (Blaberidae:
      Panesthiinae). Here, we show that physicochemical gut conditions and microbial
      fermentation products in the gut of Panesthia angustipennis resemble that of
      other cockroaches. Microsensor measurements confirmed that all gut compartments
      were anoxic at the center and had a slightly acidic to neutral pH and a negative
      redox potential. While acetate dominated in all compartments, lactate and
      hydrogen accumulated only in the crop. The high, hydrogen-limited rates of
      methane emission from living cockroaches were in agreement with the restriction
      of F420-fluorescent methanogens to the hindgut. The gut microbiota of both P.
      angustipennis and Salganea esakii differed strongly between compartments, with
      the highest density and diversity in the hindgut, but similarities between
      homologous compartments of both cockroaches indicated a specificity of the
      microbiota for their respective habitats. While some lineages were most closely
      related to the gut microbiota of omnivorous cockroaches and wood- or litter
      feeding termites, others have been encountered also in vertebrates, reinforcing
      the hypothesis that strong environmental selection drives community structure in
      the cockroach gut. 

PMID- 25764555
TI  - Quorum sensing in marine snow and its possible influence on production of
      extracellular hydrolytic enzymes in marine snow bacterium Pantoea ananatis B9.
AB  - Marine snow is a continuous shower of organic and inorganic detritus, and plays a
      crucial role in transporting materials from the sea surface to the deep ocean.
      The aims of the current study were to identify N-acyl homoserine lactone (AHL)
      based quorum sensing (QS) signaling molecules directly from marine snow particles
      and to investigate the possible regulatory link between QS signals and
      extracellular hydrolytic enzymes produced by marine snow bacteria. The marine
      snow samples were collected from the surface water of China marginal seas. Two
      AHLs, i.e. 3OC6-HSL and C8-HSL, were identified directly from marine snow
      particles, while six different AHL signals, i.e. C4-HSL, 3OC6-HSL, C6-HSL, C10
      HSL, C12-HSL and C14-HSL were produced by Pantoea ananatis B9 inhabiting natural
      marine snow particles. Of the extracellular hydrolytic enzymes produced by P.
      ananatis B9, alkaline phosphatase activity was highly enhanced in growth medium
      supplemented with exogenous AHL (C10-HSL), while quorum quenching enzyme (AiiA)
      drastically reduced the enzyme activity. To our knowledge, this is the first
      report revealing six different AHL signals produced by P. ananatis B9 and AHL
      based QS system enhanced the extracellular hydrolytic enzyme in P. ananatis B9.
      Furthermore, this study first time revealing 3OC6-HSL production by Paracoccus
      carotinifaciens affiliated with Alphaproteobacteria. 

PMID- 25764553
TI  - Archaeal community diversity and abundance changes along a natural salinity
      gradient in estuarine sediments.
AB  - Archaea are widespread in marine sediments, but their occurrence and relationship
      with natural salinity gradients in estuarine sediments is not well understood.
      This study investigated the abundance and diversity of Archaea in sediments at
      three sites [Brightlingsea (BR), Alresford (AR) and Hythe (HY)] along the Colne
      Estuary, using quantitative real-time PCR (qPCR) of 16S rRNA genes, DNA
      hybridization, Archaea 16S rRNA and mcrA gene phylogenetic analyses. Total
      archaeal 16S rRNA abundance in sediments were higher in the low-salinity brackish
      sediments from HY (2-8 * 10(7) 16S rRNA gene copies cm(-3)) than the high
      salinity marine sites from BR and AR (2 * 10(4)-2 * 10(7) and 4 * 10(6)-2 * 10(7)
      16S rRNA gene copies cm(-3), respectively), although as a proportion of the total
      prokaryotes Archaea were higher at BR than at AR or HY. Phylogenetic analysis
      showed that members of the 'Bathyarchaeota' (MCG), Thaumarchaeota and
      methanogenic Euryarchaeota were the dominant groups of Archaea. The composition
      of Thaumarchaeota varied with salinity, as only 'marine' group I.1a was present
      in marine sediments (BR). Methanogen 16S rRNA genes from low-salinity sediments
      at HY were dominated by acetotrophic Methanosaeta and putatively hydrogentrophic
      Methanomicrobiales, whereas the marine site (BR) was dominated by mcrA genes
      belonging to methylotrophic Methanococcoides, versatile Methanosarcina and
      methanotrophic ANME-2a. Overall, the results indicate that salinity and
      associated factors play a role in controlling diversity and distribution of
      Archaea in estuarine sediments. 

PMID- 25764556
TI  - Interrogation of Chesapeake Bay sediment microbial communities for intrinsic
      alkane-utilizing potential under anaerobic conditions.
AB  - Based on the transient exposure of Chesapeake Bay sediments to hydrocarbons and
      the metabolic versatility of known anaerobic alkane-degrading microorganisms, it
      was hypothesized that distinct Bay sediment communities, governed by geochemical
      gradients, would have intrinsic alkane-utilizing potential under sulfate-reducing
      and/or methanogenic conditions. Sediment cores were collected along a transect of
      the Bay. Community DNA was interrogated via pyrosequencing of 16S rRNA genes, PCR
      of anaerobic hydrocarbon activation genes, and qPCR of 16S rRNA genes and genes
      involved in sulfate reduction/methanogenesis. Site sediments were used to
      establish microcosms amended with n-hexadecane under sulfate-reducing and
      methanogenic conditions. Sequencing of 16S rRNA genes indicated that sediments
      associated with hypoxic water columns contained significantly greater proportions
      of Bacteria and Archaea consistent with syntrophic degradation of organic matter
      and methanogenesis compared to less reduced sediments. Microbial taxa frequently
      associated with hydrocarbon-degrading communities were found throughout the Bay,
      and the genetic potential for hydrocarbon metabolism was demonstrated via the
      detection of benzyl-(bssA) and alkylsuccinate synthase (assA) genes. Although
      microcosm studies did not indicate sulfidogenic alkane degradation, the data
      suggested that methanogenic conversion of alkanes was occurring. These findings
      highlight the potential role that anaerobic microorganisms could play in the
      bioremediation of hydrocarbons in the Bay. 

PMID- 25764557
TI  - Viral and grazer regulation of prokaryotic growth efficiency in temperate
      freshwater pelagic environments.
AB  - In aquatic systems, limited data exists on the impact of mortality forces such as
      viral lysis and flagellate grazing when seeking to explain factors regulating
      prokaryotic metabolism. We explored the relative influence of top-down factors
      (viral lysis and heterotrophic nanoflagellate grazing) on prokaryotic mortality
      and their subsequent impact on their community metabolism in the euphotic zone of
      21 temperate freshwater lakes located in the French Massif Central. Prokaryotic
      growth efficiency (PGE, index of prokaryotic community metabolism) determined
      from prokaryotic production and respiration measurements varied from 5 to 74%
      across the lakes. Viral and potential grazer-induced mortality of prokaryotes had
      contrasting impact on PGE. Potential flagellate grazing was found to enhance PGE
      whereas viral lysis had antagonistic impacts on PGE. The average PGE value in the
      grazing and viral lysis dominated lake water samples was 35.4% (+/-15.2%) and
      17.2% (+/-8.1%), respectively. Selective viral lysis or flagellate grazing on
      prokaryotes together with the nature of contrasted substrates released through
      mortality processes can perhaps explain for the observed variation and
      differences in PGE among the studied lakes. The influences of such specific top
      down processes on PGE can have strong implications on the carbon and nutrient
      fluxes in freshwater pelagic environments. 

PMID- 25764558
TI  - Effect of progressive inoculation of fauna-free sheep with holotrich protozoa and
      total-fauna on rumen fermentation, microbial diversity and methane emissions.
AB  - Rumen methanogenesis represents an energy waste for the ruminant and an important
      source of greenhouse gas; thus, integrated studies are needed to fully understand
      this process. Eight fauna-free sheep were used to investigate the effect of
      successive inoculation with holotrich protozoa then with total fauna on rumen
      methanogenesis. Holotrichs inoculation neither altered rumen fermentation rate
      nor diet digestibility, but increased concentrations of acetate (+15%), butyrate
      (+57%), anaerobic fungi (+0.82 log), methanogens (+0.41 log) and methanogenesis
      (+54%). Further inoculation with total fauna increased rumen concentrations of
      protozoa (+1.0 log), bacteria (+0.29 log), anaerobic fungi (+0.78 log), VFA
      (+8%), ammonia and fibre digestibility (+17%) without affecting levels of
      methanogens or methanogenesis. Rumen methanogens population was fairly stable in
      terms of structure and diversity, while the bacterial community was highly
      affected by the treatments. Inoculation with holotrich protozoa increased
      bacterial diversity. Further inoculation with total fauna lowered bacterial
      diversity but increased concentrations of certain propionate and lactate
      producing bacteria, suggesting that alternative H2 sinks could be relevant. This
      experiment suggests that holotrich protozoa have a greater impact on rumen
      methanogenesis than entodiniomorphids. Thus, further research is warranted to
      understand the effect of holotrich protozoa on methane formation and evaluate
      their elimination from the rumen as a potential methane mitigation strategy. 

PMID- 25764559
TI  - The spatial organization and microbial community structure of an epilithic
      biofilm.
AB  - Microbial biofilms are common on lithic surfaces, including stone buildings.
      However, the ecology of these communities is poorly understood. Few studies have
      focused on the spatial characteristics of lithobiontic biofilms, despite the fact
      that spatial structure has been demonstrated to influence ecosystem function (and
      hence biodegradation) and community diversity. Furthermore, relatively few
      studies have utilized molecular techniques to characterize these communities,
      even though molecular methods have revealed unexpected microbial diversity in
      other habitats. This study investigated (1) the spatial structure and (2) the
      taxonomic composition of an epilithic biofilm using molecular techniques, namely
      amplicon pyrosequencing and terminal restriction fragment length polymorphism.
      Dispersion indices and Mantel correlograms were used to test for the presence of
      spatial structure in the biofilm. Diversity metrics and rank-abundance
      distributions (RADs) were also generated. The study revealed spatial structure on
      a centimetre scale in eukaryotic microbes (fungi and algae), but not the
      bacteria. Fungal and bacterial communities were highly diverse; algal communities
      much less so. The RADs were characterized by a distinctive 'hollow' (concave up)
      profile and long tails of rare taxa. These findings have implications for
      understanding the ecology of epilithic biofilms and the spatial heterogeneity of
      stone biodeterioration. 

PMID- 25764560
TI  - Improved isolation strategies allowed the phenotypic differentiation of two
      Nitrospira strains from widespread phylogenetic lineages.
AB  - The second step of nitrification, the oxidation of nitrite to nitrate, is vital
      for the functioning of the nitrogen cycle, but our understanding of the
      ecological roles of the involved microorganisms is still limited. The known
      diversity of Nitrospira, the most widely distributed nitrite-oxidizing bacteria,
      has increased remarkably by analyses of 16S rRNA and functional gene sequences.
      However, only few representatives could be brought into laboratory cultures so
      far. In this study, two Nitrospira from activated sludge were isolated using
      novel approaches together with established methods. Highly enriched 'Candidatus
      Nitrospira defluvii' was separated from concomitant heterotrophs by taking
      advantage of its resistance against ampicillin and acriflavine. Beside this
      member of lineage I, a novel species of lineage II, named N. lenta, was initially
      enriched at 10 degrees C and finally purified by using optical tweezers. The
      tolerance to elevated nitrite levels was much higher in N. defluvii than in the
      more fastidious N. lenta and was accompanied by pronounced biofilm formation.
      Phylogenetic classification of 12 additional enrichments indicated that
      Nitrospira lineage I is common in extreme and moderate ecosystems like lineage
      II. The new cultures will help to explore physiological and genomic differences
      affecting niche separation between members of this highly diverse genus. 

PMID- 25764561
TI  - Denitrification and the denitrifier community in coastal microbial mats.
AB  - Denitrification was measured in three structurally different coastal microbial
      mats by using the stable isotope technique. The composition of the denitrifying
      community was determined by analyzing the nitrite reductase (nirS and nirK) genes
      using clone libraries and the GeoChip. The highest potential rate of
      denitrification (7.0 +/- 1.0 mmol N m(-2) d(-1)) was observed during summer at
      station 1 (supra-littoral). The rates of denitrification were much lower in the
      stations 2 (marine) and 3 (intermediate) (respectively 0.1 +/- 0.05 and 0.7 +/-
      0.2 mmol N m(-2) d(-1)) and showed less seasonality when compared to station 1.
      The denitrifying community at station 1 was also more diverse than that at
      station 2 and 3, which were more similar to each other than either of these
      stations to station 1. In all three stations, the diversity of both nirS and nirK
      denitrifiers was higher in summer when compared to winter. The location along the
      tidal gradient seems to determine the composition, diversity and activity of the
      denitrifier community, which may be driven by salinity, nitrate/nitrite and
      organic carbon. Both nirS and nirK denitrifiers are equally present and therefore
      they are likely to play a role in the denitrification of the microbial mats
      studied.

PMID- 25764562
TI  - Spatial scales of interactions among bacteria and between bacteria and the leaf
      surface.
AB  - Microbial life on plant leaves is characterized by a multitude of interactions
      between leaf colonizers and their environment. While the existence of many of
      these interactions has been confirmed, their spatial scale or reach often
      remained unknown. In this study, we applied spatial point pattern analysis to 244
      distribution patterns of Pantoea agglomerans and Pseudomonas syringae on bean
      leaves. The results showed that bacterial colonizers of leaves interact with
      their environment at different spatial scales. Interactions among bacteria were
      often confined to small spatial scales up to 5-20 MUm, compared to interactions
      between bacteria and leaf surface structures such as trichomes which could be
      observed in excess of 100 MUm. Spatial point-pattern analyses prove a
      comprehensive tool to determine the different spatial scales of bacterial
      interactions on plant leaves and will help microbiologists to better understand
      the interplay between these interactions. 

PMID- 25764563
TI  - Ammonia oxidation is not required for growth of Group 1.1c soil Thaumarchaeota.
AB  - Thaumarchaeota are among the most abundant organisms on Earth and are ubiquitous.
      Within this phylum, all cultivated representatives of Group 1.1a and Group 1.1b
      Thaumarchaeota are ammonia oxidizers, and play a key role in the nitrogen cycle.
      While Group 1.1c is phylogenetically closely related to the ammonia-oxidizing
      Thaumarchaeota and is abundant in acidic forest soils, nothing is known about its
      physiology or ecosystem function. The goal of this study was to perform in situ
      physiological characterization of Group 1.1c Thaumarchaeota by determining
      conditions that favour their growth in soil. Several acidic grassland, birch and
      pine tree forest soils were sampled and those with the highest Group 1.1c 16S
      rRNA gene abundance were incubated in microcosms to determine optimal growth
      temperature, ammonia oxidation and growth on several organic compounds. Growth of
      Group 1.1c Thaumarchaeota, assessed by qPCR of Group 1.1c 16S rRNA genes,
      occurred in soil, optimally at 30 degrees C, but was not associated with ammonia
      oxidation and the functional gene amoA could not be detected. Growth was also
      stimulated by addition of organic nitrogen compounds (glutamate and casamino
      acids) but not when supplemented with organic carbon alone. This is the first
      evidence for non-ammonia oxidation associated growth of Thaumarchaeota in soil.

PMID- 25764564
TI  - Long-term monitoring reveals stable and remarkably similar microbial communities
      in parallel full-scale biogas reactors digesting energy crops.
AB  - Biogas is an important renewable energy carrier. It is a product of stepwise
      anaerobic degradation of organic materials by highly diverse microbial
      communities forming complex interlinking metabolic networks. Knowledge about the
      microbial background of long-term stable process performance in full-scale
      reactors is crucial for rationally improving the efficiency and reliability of
      biogas plants. To generate such knowledge, in the present study three parallel
      mesophilic full-scale reactors fed exclusively with energy crops were sampled
      weekly over one year. Physicochemical process parameters were determined and the
      microbial communities were analysed by terminal restriction fragment length
      polymorphism (T-RFLP) fingerprinting and 454-amplicon sequencing. For
      investigating the methanogenic community, a high-resolution T-RFLP approach based
      on the mcrA gene was developed by selecting restriction enzymes with improved
      taxonomic resolution compared to previous studies. Interestingly, no
      Methanosarcina-related generalists, but rather specialized hydrogenotrophic and
      acetoclastic methanogenic taxa were detected. In general, the microbial
      communities in the non-connected reactors were remarkably stable and highly
      similar indicating that identical environmental and process parameters resulted
      in identical microbial assemblages and dynamics. Practical implications such as
      flexible operation schemes comprising controlled variations of process parameters
      for an efficient microbial resource management under fluctuating process
      conditions are discussed. 

PMID- 25764565
TI  - Effects of transparent exopolymer particles and suspended particles on the
      survival of Salmonella enterica serovar Typhimurium in seawater.
AB  - The bacterium Salmonella enterica can infect marine mammals and has been
      increasingly implicated in seafood-borne disease outbreaks in humans. Despite the
      risk this zoonotic agent poses to animals and people, little is known regarding
      the environmental factors that affect its persistence in the sea. The goal of
      this study was to evaluate the impact of two constituents on the survival of
      Salmonella in the marine environment: transparent exopolymer particles (TEP) and
      suspended particles. A decay experiment was conducted by spiking Salmonella into
      bottles containing seawater, seawater with alginic acid as a source of TEP,
      filtered seawater or filtered seawater with alginic acid. Survival of Salmonella
      was monitored using culture followed by enrichment assays to evaluate if the
      bacteria entered a viable but non-cultivable (VBNC) state. Salmonella cell counts
      dropped significantly faster (P <= 0.05) in the unfiltered seawater samples with
      and without TEP. The slowest decay occurred in filtered seawater containing
      alginic acid, with VBNC Salmonella persisting for 17 months. These findings
      suggest that TEP may favor Salmonella survival while suspended particles
      facilitate its decay. Insight on the survival of allochthonous, zoonotic
      pathogens in seawater can guide monitoring, management and policy decisions
      relevant to wildlife and human public health. 

PMID- 25764566
TI  - Anaerobic naphthalene degradation by sulfate-reducing Desulfobacteraceae from
      various anoxic aquifers.
AB  - Polycyclic aromatic hydrocarbons (PAH) are widespread and persistent
      environmental contaminants, especially in oxygen-free environments. The
      occurrence of anaerobic PAH-degrading bacteria and their underlying metabolic
      pathways are rarely known. In this study, PAH degraders were enriched in
      laboratory microcosms under sulfate-reducing conditions using groundwater and
      sediment samples from four PAH-contaminated aquifers. Five enrichment cultures
      were obtained showing sulfate-dependent naphthalene degradation. Mineralization
      of naphthalene was demonstrated by the formation of sulfide concomitant with the
      depletion of naphthalene and the development of (13)C-labeled CO2 from [(13)C6]
      naphthalene. 16S rRNA gene and metaproteome analyses revealed that organisms
      related to Desulfobacterium str. N47 were the main naphthalene degraders in four
      enrichment cultures. Protein sequences highly similar to enzymes of the
      naphthalene degradation pathway of N47 were identified, suggesting that
      naphthalene was activated by a carboxylase, and that the central metabolite 2
      naphthoyl-CoA was further reduced by two reductases. The data indicate an
      importance of members of the family Desulfobacteraceae for naphthalene
      degradation under sulfate-reducing conditions in freshwater environments. 

PMID- 25764567
TI  - Characterization of Staphylococcus aureus strains isolated from faeces of healthy
      neonates and potential mother-to-infant microbial transmission through
      breastfeeding.
AB  - Twenty-one women and their respective singleton infants participated in this
      study, contributing with samples of breast milk and faeces (at days 7, 14 and 35
      after birth), respectively, used for Staphylococcus aureus recovery. The aim was
      to track the carriage of S. aureus in milk and infant faeces of mother-infant
      pairs, and to determine the genetic lineages of the isolates, their potential
      clonal relationships and their content in antimicrobial resistance, virulence and
      immune evasion cluster genes. The molecular characterization was performed by PCR
      and sequencing. Clonal relationship among mother-infant isolates was conducted by
      spa typing, multilocus sequence typing (MLST), and pulsed-field gel
      electrophoresis (PFGE). Staphylococcus aureus was isolated from milk samples of 6
      of 21 mothers (16 isolates) and from faecal samples of 12 of 21 infants (25
      isolates). From these 41 S. aureus recovered, 18 were methicillin-resistant
      (MRSA) and 23 methicillin-susceptible (MSSA). Twelve diferentes spa types and
      eight sequence types were detected among S. aureus. Predominant clonal complexes
      were CC5 (43.9%) and CC30 (36.6%). MRSA strains presented a multidrug-resistance
      profile, 65.2% of MSSA strains harboured tsst-1 toxin gene and 26.8% of total
      strains carried the cna gene. A potential mother-to-infant S. aureus transmission
      was demonstrated in four cases by spa typing, MLST and PFGE (transmission of
      t322/ST5/CC5-PFGE-A, t136/ST34/CC30-PFGE-B and t021/ST1869/CC30-PFGE-C strains).
      Breastfeeding seems to contribute to early S. aureus intestinal colonization in
      neonates what might affect the immune system development. 

PMID- 25764568
TI  - A genome-based identification approach for members of the genus Bifidobacterium.
AB  - During recent years, the significant and increasing interest in novel
      bifidobacterial strains with health-promoting characteristics has catalyzed the
      development of methods for efficient and reliable identification of
      Bifidobacterium strains at (sub) species level. We developed an assay based on
      recently acquired bifidobacterial genomic data and involving 98 primer pairs,
      called the Bifidobacterium-ampliseq panel. This panel includes multiplex PCR
      primers that target both core and variable genes of the pangenome of this genus.
      Our results demonstrate that the employment of the Bifidobacterium-ampliseq panel
      allows rapid and specific identification of the so far recognized 48 (sub)species
      harboring the Bifidobacterium genus, and thus represents a cost- and time
      effective bifidobacterial screening methodology. 

PMID- 25764569
TI  - Inert ambient annealing effect on MANOS capacitor memory characteristics.
AB  - In this work we report on the influence of nitrogen ambient thermal effects on
      the performance of Pt/Al2O3/Si3N4/SiO2/Si memory capacitors. Two post deposition
      annealing (PDA) furnace steps were employed, at 850 and 1050  degrees C both for
      15 min. The alumina films were deposited by atomic layer deposition using TMA/H2O
      at 250  degrees C. The structural characteristics of the stacks were evaluated by
      transmission electron microscopy and x-ray reflectivity measurements. The memory
      performance of the stacks was evaluated by write/erase and erase/write
      measurements, endurance and retention testing. It was found that in as-deposited
      state the Al2O3 layer is defective resulting in strong leakage currents,
      controlled by deep defects states. Thus, this behavior inhibits the memory
      functionality of the stacks. PDA crystallizes and condenses the Al2O3
      transforming the layer from amorphous to polycrystalline. During this
      transformation the Al2O3 electrical quality improves greatly indicating that a
      significant number of these deep defects have been removed during annealing.
      Physical reasoning implies that the most plausible origin of these deep defects
      is hydrogen. However, the polycrystalline Al2O3 films showed inferior retention
      characteristics which are attributed to grain boundary related shallow defects.
      The findings of this work could pave the way for more efficient annealing
      schemes, in which an important factor is the time interval for hydrogen out
      diffusion from the Al2O3 layer. 

PMID- 25764571
TI  - Pt35Cu65 nanoarchitecture: a highly durable and effective electrocatalyst towards
      methanol oxidation.
AB  - Aiming at electro-catalytic performance enhancement and reduction of catalyst
      cost, PtxCu1-x (Pt35Cu65, Pt53Cu47, and Pt68Cu32) nanoarchitecture samples with
      controllable atomic composition, similar morphology and particle-size have been
      prepared by using a one-pot chemical route. The as-prepared PtxCu1-x
      nanoarchitectures are confirmed as consisting of the integration of initial small
      alloy nanoparticles (NPs), resulting in an interconnected nanoporous structure.
      The electrochemical experiments indicate that these PtxCu1-x nanocatalysts
      exhibit atomic composition dependent catalytic activity, although the surfaces of
      all the catalysts were characterized to be featured with a Pt enrichment
      structure. With optimal atomic composition, the Pt35Cu65 catalyst possesses
      enhanced electro-catalytic activities towards methanol oxidation in comparison
      with other PtxCu1-x samples and pure Pt catalyst with similar morphology.
      Furthermore, the integrated Pt35Cu65 nanoarchitecture displays good durability
      during the long term electrochemical scanning through as many as 1500 cycles. The
      comparable catalytic performance of Pt35Cu65 catalyst could be attributed to the
      interconnected initial small NPs, formation of open porous structure, durable
      nanoarchitecture, and synergetic effect of the alloyed atoms. The structural
      evolution from metastable small alloy NPs to integrated stable nanoarchitectures
      may provide new opportunities to design and prepare novel composite materials
      with durable structure and effective catalytic properties. 

PMID- 25764570
TI  - Inducing cells to disperse nickel nanowires via integrin-mediated responses.
AB  - We present non-cytotoxic, magnetic, Arg-Gly-Asp (RGD)-functionalized nickel
      nanowires (RGD-nanowires) that trigger specific cellular responses via integrin
      transmembrane receptors, resulting in dispersal of the nanowires. Time-lapse
      fluorescence and phase contrast microscopy showed that dispersal of 3 MUm long
      nanowire increased by a factor of 1.54 with functionalization by RGD, compared to
      polyethylene glycol (PEG), through integrin-specific binding, internalization and
      proliferation in osteosarcoma cells. Further, a 35.5% increase in cell density
      was observed in the presence of RGD-nanowires, compared to an increase of only
      15.6% with PEG-nanowires. These results promise to advance applications of
      magnetic nanoparticles in drug delivery, hyperthermia, and cell separation where
      uniformity and high efficiency in cell targeting is desirable. 

PMID- 25764572
TI  - Authors' response.

PMID- 25764573
TI  - Author's response.

PMID- 25764574
TI  - Diabetes patients more susceptible to flu complications.

PMID- 25764575
TI  - Promising results Halt phase III studies of idelalisib.

PMID- 25764576
TI  - Reversing Halt, FDA reauthorizes sale of ponatinib.

PMID- 25764577
TI  - Post marketing research no longer an afterthought with targeted therapies.

PMID- 25764578
TI  - When less is more: results Herald 'paradigm shift' in treating newly diagnosed
      multiple myeloma patients.

PMID- 25764579
TI  - Collaboration between academia and pharma to bring new therapies to market more
      important than ever.

PMID- 25764580
TI  - As genomics reveals diversity of lymphomas, questions arise on diagnosis,
      treatment, and ethical issues.

PMID- 25764581
TI  - GSK drug combination approved for advanced melanoma.

PMID- 25764582
TI  - A glimpse into managed care of diagnostics.

PMID- 25764583
TI  - WellPoint initiative may challenge some practices.

PMID- 25764584
TI  - Group A. Initiator paper. Plaque control: home remedies practiced in developing
      countries.

PMID- 25764585
TI  - Group A. Reactor Paper. Plaque control: home remedies practiced in developing
      countries.

PMID- 25764586
TI  - Group A. Consensus paper. Plaque control--home remedies practiced in developing
      countries.

PMID- 25764587
TI  - Group B. Initiator paper. Non-surgical periodontal therapy: mechanical
      debridement, antimicrobial agents and other modalities.

PMID- 25764588
TI  - Group B. Reactor report. Non-surgical periodontal therapy: mechanical
      debridement, antimicrobial agents and other modalities.

PMID- 25764589
TI  - Group B. Consensus paper. Non-surgical periodontal therapy: mechanical
      debridement, antimicrobial agents and other modalities.

PMID- 25764590
TI  - Group C. Initiator paper. Periodontal regeneration--fact or fiction?
AB  - Numerous techniques have been tried and tested to regenerate tissues lost to
      periodontal disease. While there has been some success to date, more work is
      required to move this to a reliable and clinically predictable procedure. Much of
      the future success for such treatments will rely largely on our understanding of
      the biology of both developmental and regenerative processes. Nonetheless,
      despite the noble goal of periodontal regeneration, the relevance of re-creation
      of a connective tissue attachment has been questioned. Since formation of a long
      junctional epithelial attachment to the tooth following a variety of periodontal
      treatment procedures has been shown to be no more susceptible to further
      breakdown than a non-diseased site, the question arises as to what purpose do we
      seek the ultimate outcome of periodontal regeneration? The answer lies in the
      "fact and fiction" of periodontal regeneration. There is no doubt that the
      regenerative procedures that have been developed can be shown to be biologically
      successful at the histological level. Furthermore, the results of periodontal
      regeneration (particularly guided tissue regeneration) have been stable over the
      long term (at least up to 10 years). However, the techniques currently under use
      which show the greatest promise (guided tissue regeneration and growth factors)
      are still clinically unpredictable because of their highly technique-sensitive
      nature. In addition, whether the slight clinical improvements offered by these
      procedures over routine open flap debridement procedures are of cost or patient
      benefit with regards to improved periodontal health and retention of teeth
      remains to be established. The next phase in regenerative technologies will
      undoubtedly involve a deeper understanding of the molecular signaling (both intra
      and extra-cellular) and cellular differentiation processes involved in the
      regenerative processes. So in answer to the question of whether periodontal
      regeneration is fact or fiction, the answer clearly is that it is both. However,
      with more work it will become established fact with little fiction and the
      desired clinical endpoint of predictable regeneration of the periodontal tissues
      damaged by inflammation to their original form and function will be achieved.

PMID- 25764591
TI  - Group C. Reactor paper. Periodontal regeneration--fact or fiction?

PMID- 25764592
TI  - Group C. Consensus paper. Periodontal regeneration--fact or fiction?

PMID- 25764593
TI  - Group D. Initiator paper. Implants--peri-implant (hard and soft tissue)
      interactions in health and disease: the impact of explosion of implant
      manufacturers.
AB  - 1. The best-documented implants have a threaded solid screw-type design and are
      manufactured from commercially pure (grade IV) titanium. There is good evidence
      to support implants >= 6 mm in length, and >= 3 mm in diameter. 2. Integrity of
      the seal between the abutment and the implant is important for several reasons,
      including minimization of mechanical and biological complications and maintaining
      marginal bone levels. Although the ideal design features of the implant-abutment
      connection have not been determined, an internal connection, micro-grooves at the
      implant collar, and horizontal offset of the implant-abutment junction (platform
      switch) appear to impart favorable properties. 3. Implants with moderately rough
      implant surfaces provide advantages over machined surfaces in terms of the speed
      and extent of osseointegration. While the favorable performances of both
      minimally and moderately rough surfaces are supported by long-term data,
      moderately rough surfaces provide superior outcomes in compromised sites, such as
      the posterior maxilla. 4. Although plaque is critical in the progression of peri
      implantitis, the disease has a multi-factorial aetiology, and may be influenced
      by poor integrity of the abutment/implant connection. Iatrogenic factors, such as
      the introduction of a foreign body. (e.g., cement) below the mucosal margin, can
      be important contributors. 5. Clinicians should exercise caution when using a
      particular implant system, ensuring that the implant design is appropriate and
      supported by scientific evidence. Central to this is access to and participation
      in quality education on the impact that implant characteristics can have on
      clinical outcomes. Caution should be exercised in utilizing non-genuine
      restorative componentry that may lead to a poor implant-abutment fit and
      subsequent technical and biological complications.

PMID- 25764594
TI  - Group D. Reactor report. Implants--peri-implant (hard and soft tissue)
      interactions in health and disease: the impact of explosion of implant
      manufacturers.

PMID- 25764595
TI  - Group D. Consensus report. Implants--peri-implant (hard and soft tissue)
      interactions in health and disease: the impact of explosion of implant
      manufacturers.

PMID- 25764596
TI  - Group E. Initiator paper. Interprofessional education and multidisciplinary
      teamwork for prevention and effective management of periodontal disease.

PMID- 25764597
TI  - Group E. Reactor report. Enhancing global periodontal and oral health by
      standardizing education systems.

PMID- 25764598
TI  - Group E. Consensus paper. Interprofessional education and multidisciplinary
      teamwork for prevention and effective management of periodontal disease.

PMID- 25764599
TI  - Violent patients are more than just occupational hazards.

PMID- 25764600
TI  - Avoid payment delays by ramping up for ICD-10.

PMID- 25764601
TI  - Research aims to discover what works and for which patients.

PMID- 25764602
TI  - Medicaid projects set to evaluate IMD-exclusion alternatives.

PMID- 25764603
TI  - Leverage effective marketing in a post-ACA environment.

PMID- 25764604
TI  - Integration trend drives today's accreditation outlook.

PMID- 25764605
TI  - Austin Oaks Hospital aims to create a homelike atmosphere.

PMID- 25764606
TI  - Liver function tests abnormality and clinical severity of dengue infection in
      adult patients.
AB  - BACKGROUND: The clinical manifestations of dengue infection in the adult are
      different from those in children, i.e. having less prevalence to bleeding, and
      more commonly, abnormal liver function tests. OBJECTIVE: The primary objective is
      to describe the clinical manifestations of dengue infection in adult patients.
      The secondary objective is to compare the clinical manifestations of dengue
      infection between the groups of normal and abnormal liver function tests in adult
      patients. MATERIAL AND METHOD: Retrospective study was done in adults (age 15
      years) dengue patients admitted at the Hospital for Tropical Diseases from 2000
      2002. Dengue infection diagnosed by WHO clinical criteria 1997 with serological
      tests confirmed by ELISA test or Rapid Immunochromatographic test. Liver function
      test was recorded by day of fever. RESULTS: There were 127 adult dengue patients
      with mean age 26.4 +/- 11.5 years. Classifications of dengue infection by WHO
      criteria were DF 4.7%, DHF grade 126.0%, DHF grade 2 63.0% and DHF grade 3 6.3%.
      Mean duration of fever clearance time was 6.0 +/- 1.9 days but the fever lasted
      longer in cases of high-level transaminases (> 10 folds). The common presenting
      symptoms and signs were myalgia (95.9%), nausea/vomiting (87.7%), positive
      tourniquet test (77.2%), abdominal pain (42.7%), hepatomegaly (34.6%), and
      bleeding (20.5%). The ratio of AST and ALTwas 1.8:1. Abnormal AST and ALT were
      found in 88.2% and 69.3% of the patients, respectively. Patients with
      nausea/vomiting, petechiae or duration of fever > 7 days more frequently had
      abnormal transaminases. Abnormal AST during the febrile stage was associated with
      bleeding. High-level AST and ALT occurred in 11.0% and 7.0%, respectively. Shock
      was associated with high-level ALT during the febrile stage. CONCLUSION: Adult
      dengue patients commonly showed abnormal liver function tests and accounted for
      at least two-thirds of them. High-level ALT during the febrile stage showed
      association with shock.

PMID- 25764607
TI  - A reduction of asymmetric dimethylarginine in renal transplant recipients
      receiving sirolimus-based regimen.
AB  - OBJECTIVE: Sirolimus may be of benefit in terms ofa reduction of cardiovascular
      disease in renal transplant recipients. The aim of the present study was to
      investigate cardiovascular risk markers in renal transplant recipients receiving
      calcineurin inhibitors (CNI-based regimen), as compared to those receiving
      sirolimus (SRL-based regimen). MATERIAL AND METHOD: 42 patients were recruited
      (21 patients for each regimen). Plasma concentrations of cardiovascular risk
      markers, including asymmetric dimethylarginine (ADMA), nitric oxide (NO),
      homocysteine (Hcy), and total antioxidant status (TAOS) were measured. RESULTS:
      Plasma ADMA concentrations were lower in patients with SRL-based regimen, as
      compared to those with CNI-based regimen (0.52 +/- 0.02 and 0.60 +/- 0.02
      MUmol/L, p = 0.027). There were no statistically significant differences seen in
      NO, Hcy, and TAOS between the two treatments. CONCLUSION: As compared to CNI
      based regimen, cardiovascular risk marker (ADMA) levels are lower in patients
      with SRL-based regimen.

PMID- 25764608
TI  - A cost-utility analysis of laparoscopic radical prostatectomy and robotic
      assisted laparoscopic radical prostatectomy in men with localized prostate cancer
      in Thailand.
AB  - OBJECTIVE: Robotic machines are being used with increasing frequency in the
      treatment of clinically localized prostate cancer in Thailand. While robotics may
      offer some advantages, it remains unclear whether potential benefits offset
      higher costs. The objective of this study was to evaluate and compare cost
      utility between standard and robotic-assisted laparoscopic prostatectomy from a
      health system perspective. MATERIAL AND METHOD: The authors created a care
      pathway and a model to facilitate a comprehensive cost utility analysis. All
      variables used in our model were derived from our review of the literature,
      exceptfor cost, utility for erectile dysfunction, and utility for urinary
      incontinence, which were derived from Chulalongkorn Hospital patient records. All
      costs described in this report are denominated in Thai baht, with a 2012 currency
      value. A positive margin was used to simulate the model. Sensitivity analysis was
      performed to estimate the robustness of the outcome. RESULTS: Thailand utility
      values for erectile dysfunction and urinary incontinence were 0.86 and 0.81,
      respectively. The cost of robotic laparoscopy was, on average, 120,359 baht (95%
      CI, 89,368-151,350 baht) higher than standard laparoscopy and was more effective
      with a mean gain of 0.05 quality-adjusted life years (QALYs) (95% CI, 0.03-0.08)
      for the 100 procedures performed each year. The incremental cost effectiveness
      (ICER) ratio was 2,407,180 baht per QALYs, with a very low probability that
      robotic prostatectomy would be cost effective at the Thai-willingness-to pay
      (WTP) threshold of 160,000 baht/ QALY. CONCLUSION: Robotic-assisted laparoscopic
      prostatectomy is not more cost effective than standard laparoscopic prostatectomy
      for the 100 cases performed each year. An increase in the number of cases may
      result in better economies of scale and a lower ICER, an outcome that may
      increase the overall value and cost effectiveness of an investment in this
      technology.

PMID- 25764609
TI  - Effect of a low-carbohydrate diet on respiratory quotient of infants with chronic
      lung disease.
AB  - OBJECTIVE: To compare the respiratory quotient in infants with chronic lung
      disease before and after receiving a modular diet with slightly lower
      carbohydrate content. MATERIAL AND METHOD: Infants with chronic lung disease from
      the King Chulalongkorn Memorial Hospital were enrolled and assessed for
      nutritional status, severity of chronic lung disease and dietary intake. Indirect
      calorimetry was performed using a custom-made airtight canopy with O2 and CO2
      sensors. Respiratory quotient (RQ) was calculated from VCO2/VO2 during the period
      they were fed low carbohydrates (37% of total calories) for at least 24 hours vs.
      a standard diet (47% carbohydrate). These two formulas were similar in terms of
      caloric density and protein content. Each patient received at least 100-150 kcal/
      kg/day during the study period. Respiratory quotients of the same patient
      receiving the two diets were compared by using Wilcoxon signed-rank test.
      RESULTS: A total of 14 patients (median age 7 months, range 1-26 months) were
      recruited. Twelve children had weight for age Z-score below-2SD. Their median
      weight for age Z-score, length for age Z-score and weight for length Z-score were
      -2.89, -3.08 and -1.24, respectively. The median RQ measured during the low
      carbohydrate diet was 0.96 (interquartile range 0.95-0.97), significantly lower
      than the median RQ during the standard diet, which was 1.04 (0.97-1.10). However,
      the respiratory rate revealed no significant difference. Two participants with
      underlying gastroesophageal reflux disease showed higher RQ after low
      carbohydrate formula feeding, which might be a result of hypersecretion due to
      its high fat content. CONCLUSION: Diet with slightly lower carbohydrate content
      can reduce the RQ in infants with chronic lung disease compared to the standard
      enteral formula. A 10-percent reduction of carbohydrate content may provide a
      sizeable effect in this group of patients. Nevertheless, the clinical
      significance of this finding requires further investigation.

PMID- 25764610
TI  - Complete genome characterization and phylogenetic analysis of WU polyomavirus in
      Thai pediatric patients with respiratory tract infections in 2013.
AB  - BACKGROUND: The WU polyomavirus (WUPyV) is a small DNA virus (family
      Polyomaviridae) that contains a circular double-stranded DNA genome,
      approximately 5 kb in length. WUPyV was first discovered in the respiratory tract
      of children with acute respiratory symptoms. OBJECTIVE: This study focuses on the
      complete genome characterization and phylogenetic analysis of WUPyV obtained from
      Thai patients with respiratory diseases in 2013. MATERIAL AND METHOD: DNA was
      extracted from nasopharyngeal (NP) suction specimens (n = 614) from patients with
      respiratory tract infections. WUPyV was detected by using semi-nested PCR and
      then characterized by whole genome sequencing. The nucleotides and deduced amino
      acid sequences were analyzed by multiple sequences alignment and phylogenetic
      tree. RESULTS: Analysis revealed that 0.16% (1/614) of the sample was positive
      for WUPyV. Phylogenetic trees demonstrated that WUPyV(isolate CU_Chonburi 3) was
      closely related to previously described WUPyV. Moreover, whole genome sequences
      alignment of WUPyV showed several nucleotide variations within non-coding regions
      and amino acid changes in VP1 (position S347T); VP2 (positions L40V, G120R,
      Y121I, P123R, G127S, L137F, Q287R, and A327V); LTAg (positions Q357P, V369E,
      E377K, D378V, A381T, R382E, R383G, and D389G); and, STAg (positions R139S, K141E,
      R148K, and W153C). CONCLUSION: Nucleotide variations within non-coding regions
      and critical amino acid substitutions in viral proteins may affect the rate of
      viral replication and viral adaptation; factors that may be linked to the
      susceptibility and severity of viral infection. Data obtained from this study may
      be useful in better understanding the genetic characterization and mutation
      patterns of WUPyV.

PMID- 25764611
TI  - Quantitative urine hCG and urine pregnancy test in gestational trophoblastic
      disease patients with low hCG titer.
AB  - OBJECTIVE: To study the correlation between serum and urine hCG levels in
      gestational trophoblastic disease (GTD) patients with low hCG level. The
      correlation between serum hCG and results from urine pregnancy tests are
      evaluated along with quantitative measurement. MATERIAL AND METHOD: In this
      prospective study, 86 cases of gestational trophoblastic disease patients with
      positive and low level of serum hCG (< 100 mIU/ml) were recruited. Quantitative
      serum hCG urine hCG and urine pregnancy test were performed. The correlation
      coefficients between serum and urine hCG were then analyzed by SPSS 16.0.
      Furthermore, the levels of serum hCG were compared to the results of the urine
      pregnancy test. RESULTS: From February 2006 to June 2008, 86 cases were recruited
      for this study. The correlation coefficient between serum and urine hCG levels in
      all cases was 0.44 (using Pearson correlation), p = 0.01. In subgroup analysis,
      the correlation coefficient between serum and urine hCG levels in chemosensitive
      gestational trophoblastic neoplasia (GTN) patients (n = 27) was 0.73, p <= 0.01.
      The correlation coefficient in chemoresistant GTN patients (n = 38) was 0.29, p =
      0.07; and the correlation coefficient in hydatidiform mole patients (n = 21) was
      0.47, p = 0.03. A urine pregnancy test was positive only in 10 of 86 specimens.
      CONCLUSION: The correlation coefficient between serum and urine hCG in GTD
      patients with low hCG level showed significant correlation. However, patients
      with chemoresistance had less correlation than those with chemosensitivity and
      hydatidiform mole. Urine pregnancy test had low correlation with urine hCG and
      was not useful in this group of patients.

PMID- 25764612
TI  - Low urine output during the first twenty-four hours after total knee
      arthroplasty.
AB  - BACKGROUND: Low urine output (LUO) for six hours is defined as the stage that is
      at risk of acute renal failure. Major surgeries with a bloodless field, such as
      total knee arthroplasty (TKA), may be associated with LUO; however; there has
      been no study addressing this point. The present study evaluated the incidence of
      LUO and the effect of fluid balance on LUO in TKA patients during the first 24
      hours after surgery. MATERIAL AND METHOD: The authors retrospectively evaluated
      257 uncomplicated patients undergoing unilateral TKA during the first 24 hours
      after surgery. Patients' demographic data, intra-operative intravenous (IV) fluid
      replacement, postoperative IV fluid replacement, oral fluid intake, total fluid
      intake, postoperative urine output, blood collected from the drain, and the total
      visible fluid output during the first 24 hours after surgery were collected and
      evaluated. RESULTS: The incidence of LUO was 19.1% (49/257) in the studied group.
      There were no significant differences in patients' demographic data between the
      LUO and normal urine output (NUO) groups. Comparing the LUO and NUO groups, the
      LUO group had a lower volume of intra-operative fluid replacement, with
      statistical significance. There were no differences in postoperative IV fluid
      replacement and postoperative oral fluid intake between groups. Although 80.5% of
      the studied group had LV fluid replacement at a less than ideal level, at
      discharge there was no patient suffering from renal complications related to LUO.
      DISCUSSION AND CONCLUSION: Urine output is one of the common monitoring
      parameters of fluid balance in the perioperative period; it should be >= 0.5
      mL/kg/h. Prolonged low urine output for six hours and for 12 hours are
      categorized as causing risk and injury to the kidney, respectively. The incidence
      of LUO at our institution during the first 24 hours after TKA is not uncommon and
      is significantly related to intra-operative fluid replacement. Fortunately, all
      LUO patients had further fluid replacement, resulting in no renal complications
      at discharge. As eighty percent of patients had less than ideal fluid
      replacement, and patients having LUO during the first 24 hours had a
      significantly lower volume of intra-operative fluid replacement, the authors
      propose reconsidering perioperative fluid replacement in TKA patients, especially
      intra-operative IV fluid to avoid LUO.

PMID- 25764613
TI  - A comparison of the effectiveness of radial extracorporeal shock wave therapy and
      ultrasound therapy in the treatment of chronic plantar fasciitis: a randomized
      controlled trial.
AB  - OBJECTIVE: To compare the effectiveness ofradial extracorporeal shock wave
      therapy (rSWET) and ultrasound therapy (US) in the treatment of chronic plantar
      fasciitis. STUDY DESIGN: Randomized controlled trial. SETTING: Department of
      Rehabilitation Medicine, King Chulalongkorn Memorial Hospital. MATERIAL AND
      METHOD: Thirty patients who were diagnosed with plantar fasciitis for at least 3
      months and who had not responded to other forms of conservative treatment were
      recruited for this study. They were randomly divided into two groups of 15
      patients. The rESWT group was treated with 1 session per week and the US group
      with 3 sessions per week, with both groups undergoing a total of 6 consecutive
      weeks of treatment. Visual analog scale (VAS) assessments were performed before
      and after treatment at 1, 3, 6, 12, and 24 weeks. The mobility subscale of the
      plantar fasciitis pain and disability scale (PFPS) was measured before and after
      treatment. Patient satisfaction was evaluated at the conclusion of the 6-week
      treatment protocol. RESULTS: VAS pain intensity scores were significantly
      decreased in both groups (p < 0.001), when measured after treatment at 1, 3, 6,
      12, and 24 weeks. The VAS pain scores for the rESWT group dropped significantly
      more than those of the US group (p < 0.001). At the end of treatment, the PFPS
      mobility subscale scores in both groups were significantly decreased (p < 0.001).
      Similar to the VAS pain score outcome, the PFPS mobility subscale score for the
      rESWT group decreased significantly more than that of the US group (p < 0.001).
      Patient satisfaction was significantly higher in the rESWT group, relative to the
      US group (p = 0.025). CONCLUSION: In chronic plantar fasciitis treatment, both
      rESWT and US were found to be effective in reducing pain and increasing mobility;
      however, statistical analysis showed that rESWT is significantly more effective
      than US.

PMID- 25764614
TI  - Anterior tibial translation sign: factors affecting interpretation of anterior
      cruciate ligament tear.
AB  - OBJECTIVE: To demonstrate factors that can affect interpretation of ACL tear
      using anterior tibial translation sign and to compare the cut-off value of
      anterior tibial translation sign in the present study with previous studies.
      MATERIAL AND METHOD: This was a retrospective descriptive research study. The
      authors included all patients who underwent both MRI and arthroscopy of the knee
      in King Chulalongkorn Memorial Hospital from January 2002 to March 2010. Anterior
      tibial translation distance was measured. For patients with intact A CL, tests
      for correlation between anterior tibial translation distance and demographic data
      were performed. For patients with ACL tear, a receiver operating characteristic
      (ROC) analysis was performed in order to determine the best cut-off value for an
      anterior tibial translation sign. RESULTS: One hundred seventeen patients were
      enrolled in this study and classified as follows: intact ACL (n = 58), partial
      ACL tear (n = 19), and complete ACL tear (n = 40). Anterior tibial translation
      distances for each subgroup were 1.5, 5.0, and 7.6mm, respectively. Significant
      mean distance differences for each pair of subgroups were found. No significant
      correlations between anterior tibial translation distance and sex, height, and
      weight were found. There was, however, a significant correlation between anterior
      tibial translation distance and age. For diagnosis of partial and complete ACL
      tear cut-off distances of 3.5 mm and 5.5 mm provided the best accuracy,
      respectively. CONCLUSION: There is correlation between anterior tibial
      translation distance and age. The authors may possibly imply that, using anterior
      tibial translation distance in young age group patients for diagnosing ACL tear
      may increase the false-positive rate. The authors introduce a cut-off distance of
      3.5 mm to classify patients as having intact ACL or ACL tear.

PMID- 25764615
TI  - Randomized cinefluoroscopic comparison of cervical spine motion using McGrath
      series 5 and Macintosh laryngoscope for intubation with manual in-line
      stabilization.
AB  - BACKGROUND: Intubation in patients with suspected cervical spine injury must be
      cautiously performed to avoid any further neurologic trauma. Several intubation
      techniques have been introduced to minimize cervical spine motion such as the use
      of the videolaryngoscope. OBJECTIVE: The present study aims to compare the
      movement of the cervical spine during intubation by using McGrath series 5
      videolaryngoscope (MGL) and that of the conventional Macintosh laryngoscope from
      cinefluoroscopic imaging. MATERIAL AND METHOD: Twenty-two patients undergoing
      elective orthopedic surgery that did not involve cervical spine procedure and
      required general anesthesia were recruited into the study. All patients were
      randomized either to have intubation with MGL (n = 11) or Macintosh laryngoscope
      (n = 11) in a neutral position with manual in-line stabilization (MILS). The
      primary outcome was the cervical vertebral angle changes pre- and post
      intubation, measured by cinefluoroscopy. The number of intubation attempts, the
      laryngoscopic view, the time to intubation, and the incidence ofany complications
      were recorded as well. RESULTS: Eleven patients were included in each group
      without any exclusion from the study. The cervical vertebral angle changes pre-
      and post-intubation with the MGL was less than with the Macintosh laryngoscope at
      C3/4 (2.00 vs. 4.27 degrees, respectively; p-value = 0.034) and the cumulative
      changes of all cervical spine levels (9.18 vs. 17.18 degrees, respectively; p
      value = 0.017). However, the time to intubation with the MGL was longer (35.07
      vs. 23.21 seconds, p-value = 0.004), the laryngoscope view was better. There were
      no statistically significant differences in the intubation success rate, the
      number of attempts, and the incidence of complications. CONCLUSION: Orotracheal
      intubation with MGL provided less cervical spine motion and improved
      visualization of the vocal cords, without causing adverse consequences as
      compared with Macintosh laryngoscope and MILS.

PMID- 25764616
TI  - Bacteriological findings and antimicrobial susceptibility pattern of isolated
      pathogens from visual threatening ocular infections.
AB  - OBJECTIVE: To study the profiles and antimicrobial susceptibility pattern of
      isolated bacteria from visual threatening ocular infection. MATERIAL AND METHOD:
      This is a retrospective review of all microbiological culture reports from visual
      threatening ocular infection patients admitted at King Chulalongkorn Memorial
      Hospital from 2005 to 2009. The culture reports with antimicrobial susceptibility
      pattern were analyzed and correlated with clinical presentation. RESULTS: There
      were 682 specimens from 282 patients (286 eyes). Three most common diagnoses were
      corneal ulcer, endophthalmitis and scleritis, which yielded positive culture of
      31.1% (38/122 eyes), 24.2% (25/103 eyes), and 55.6% (5/9 eyes), respectively.
      Overall, positive cultures were demonstrated from 77 eyes (27%). Pseudomonas
      aeruginosa was the most common causative pathogens of corneal ulcer and
      scleritis, while Enterococcus faecalis was the most common pathogens of
      endophthalmitis. All isolated Pseudomonas spp. were susceptible to ciprofloxacin
      with 4% resistance to both gentamicin and amikacin. Enterococcus faecalis
      demonstrated 50% of intermediate resistance to ciprofloxacin. There was no
      methicillin-resistant Staphylococcus aureus identified. CONCLUSION: Overall
      positive cultures obtained from visual threatening ocular infection from a 5 year
      review were 27%. Microbial profile remained stable from 2005 to 2009, and
      antimicrobial resistance was not obviously observed in our study. The findings
      may be used as guidelines for the prompt management of antimicrobial agents used
      in presumed severe bacterial ocular infection, in order to prevent devastating
      ocular tissue damage.

PMID- 25764617
TI  - Chulalongkorn vestibular balance exercise for rehabilitation in persons with
      various types of vestibular disorders.
AB  - OBJECTIVE: To study the efficiency of Chulalongkorn vestibular balance exercise
      for rehabilitation in persons with various types of vestibular disorders.
      MATERIAL AND METHOD: Fifty-eight patients with various types of vestibular
      disorder were identified by a retrospective chart review. Thirty of the 58
      patients met the inclusion criteria of having dizziness and unsteadiness post
      vestibular diseases with complete record of neuro-otologic examination;
      vestibular tests and had been followed-up for at least 3 month. These patients
      were treated with Chulalongkorn vestibular balance exercise and were evaluated
      for dizziness symptoms and balance bedside test at the beginning of treatment,
      one month and three months after the exercise. RESULTS: The average age of the
      patients was 50.34 +/- 14.04 years. The average of duration of exercise program
      was 5.6 months. There were 6 cases of vestibular neuronitis; 5 cases of post
      acoustic neuroma removal; 4 cases of acute cochleovestibular loss; 3 cases of
      motion sickness; 2 cases of cerebellar atrophy; 3 cases of multisensory
      dizziness; 4 cases of post meningitis with deafness; and 3 cases of ototoxicity.
      After the exercise, improvement of dizziness symptoms could be found in all
      groups of the diseases at one month and three months. The objective of balance
      bedside test was improved in most cases except motion sickness, multisensory
      dizziness and cerebellar atrophy. The overall percentage of improvement of
      dizziness was statistically significant at one month and three months (p = 0.0373
      and p < 0.001). However the overall balance bedside test was statistically
      improved at three months after the exercise (p = 0.034). CONCLUSION:
      Chulalongkorn vestibular balance exercise gave significantly effective results in
      the treatment of dizziness and unsteadiness from various types of vestibular
      disorder. This study demonstrated improvement of dizziness symptom post-exercise
      at one month and three months with statistical significance. The balance bedside
      test was also statistically significant improved at three months post-exercise.

PMID- 25764618
TI  - Development of a lateral-flow immunochromatographic strip using gold
      nanoparticles for Helicobacter pylori detection.
AB  - Helicobacter pylori (H. pylori) plays an important role in the development of
      chronic gastritis, peptic ulcer diseases, gastric adenocarcinoma, and gastric
      mucosal associated lymphoid tissue (MALT) lymphoma. The standard methods of
      bacterial staining, bacterial culture, and urease testfor the detection of H.
      pylori are time consuming and invasive. Non-invasive testing plays a significant
      role in the test-and-treat approach to H. pylori management. Lateral flow
      immunoassay (LFIA) is a promising method for pathogenic detection that is fast,
      easy to use, and low cost. In the present study, the authors developed an H.
      pylori LFIA strip using gold nanoparticles for H. pylori detection. The results
      reported that 20 MUg of anti-H. pylori antibody mixed with 1 mL AuNPs solution
      and incubated for 2 hours was the best concentration preparation for application
      coverage over the gold nanoparticle surface. The limit of detection observable by
      the naked eye was 15 MUg of H. pylori protein lysate. The findings of this study
      suggest the possible future development of an H. pylori LFLA strip for fast, easy
      to use, and low-cost diagnostic testing.

PMID- 25764619
TI  - Upregulation of inducible nitric oxide synthase and nitrotyrosine expression in
      primary knee osteoarthritis.
AB  - BACKGROUND: To investigate nitrite and inducible nitric oxide synthase (iNOS)
      levels in the plasma and synovial fluid of patients with primary knee
      osteoarthritis (OA) and to determine protein nitrotyrosine in synovial tissue of
      OA patients. MATERIAL AND METHOD: Thirty patients and 30 healthy controls were
      recruited into the present study. Plasma and synovial fluid nitrite levels were
      measured using Griess reaction. Plasma and synovial fluid iNOS concentrations
      were analyzed by enzyme-linked immunosorbent assay. Nitrotyrosine was detected
      immunohistochemically in synovial tissue of OA patients. RESULTS: Plasma and
      synovial fluid nitrite concentration in the OA group were significantly higher
      than those in the healthy control group were (p = 0.007 and p = 0.012).
      Furthermore, plasma iNOS levels were significantly higher in the OA group than
      those in healthy control group were (p = 0.04). Moreover, nitrotyrosine was
      detected immunohistochemically in macrophages, synovial lining layer and
      synoviocytes of synovial tissue in the OA group. CONCLUSION: These findings
      indicate that reactive nitrogen species and nitrotyrosine-containing proteins may
      be involved in the joint destruction process, and play a potential role in the
      pathogenesis of knee osteoarthritis.

PMID- 25764620
TI  - Anticancer activity of selected Colocasia gigantia fractions.
AB  - The objective of this study is to investigate the anticancer potential of the
      extract of Colocasia gigantea C. gigantea), a plant member of the Araceae family.
      In the present study, we investigated the cytotoxic activity of C. gigantea
      extract on cervical cancer (Hela) and human white blood cells (WBC) in vitro. The
      authors then identified the bioactive ingredients that demonstrated cytotoxicity
      on tested cells and evaluated those bioactive ingredients using the bioassay
      guided fractionation method. The results showed that not all parts of C. gigantea
      promote cytotoxic activity. The dichloromethane leaf fraction showed significant
      cell proliferation effect on Hela cells, but not on WBCs. Only the n-hexane tuber
      fraction (Fr. 1T) exhibited significant cytotoxicity on Hela cells (IC50 = 585
      MUg/ml) and encouraged WBC cell proliferation. From GC-Mass spectrometry, 4,22
      Stigmastadiene-3-one, Diazoprogesterone, 9-Octadecenoic acid (Z)-, hexyl ester
      and Oleic Acid were the components of Fr 1T that demonstrated cytotoxic
      potential. In conclusion, C. gigantea's Fr 1T shows potential for cervical cancer
      treatment.

PMID- 25764621
TI  - New PFO device for closure of patent foramen ovale in patients who had a history
      of cryptogenic stroke; a report of 14 cases.
AB  - OBJECTIVE: The Cocoon PFO Occluder is a device for percutaneous closure of inter
      atrial communications. Its self-centering characteristics make it attractive for
      closure of patent foramen ovales (PFOs) with or without atrial septal aneurysms.
      The goal of this study is to report the immediate and follow-up results of the
      first 14 patients in implanted with the Cocoon PFO Occluder. MATERIAL AND METHOD:
      This is a retrospective report of immediate and short-term clinical and
      echocardiographic outcome of patients who underwent transcatheter closure of PFO
      because of paradoxical embolism. Procedural success was defined as successful
      deployment of the device and effective occlusion (no, or trivial, shunt after
      device placement). All patients had a transesophageal echocardiography (TEE) with
      saline contrast injection at baseline and clinical follow-up at 6 months.
      RESULTS: Between September 2012 and March 2014, 14 patients had successfully
      undergone transcatheter closure of PFO using Cocoon device. During follow-up none
      of the patients had a recurrence of stroke after device closure. No residual
      shunt was observed in any patients at follow-up. CONCLUSION: Transcatheter
      closure of PFO with the Cocoon PFO device is safe and effective and can be used
      for preventing recurrent strokes in patients who present with cryptogenic stroke
      and PFO.

PMID- 25764622
TI  - Treatment of venous thromboembolism in the era of non-vitamin K antagonist oral
      anticoagulants.
AB  - Venous thromboembolism (VTE) is a common cause of cardiovascular morbidity and
      mortality. Heparins and warfarin have been the standard treatment of VTE for
      decades, but they have several disadvantages, e.g. parenteral route, narrow
      therapeutic window and numerous drug interactions. The development of new, non
      vitamin K antagonist oral anticoagulants (NOACs) that can overcome these problems
      is a significant breakthrough and may replace warfarin for treatment of VTE.
      However, NOACs have some limitations, e.g. the lack of antidotes and high cost.
      As a result, many physicians are uncomfortable to employ NOACs in daily practice.
      This review will briefly summarize and update pharmacological profiles, evidence
      base for VTE treatment from Phase III clinical trials and some clinical
      considerations of NOACs in treatment of VTE.

PMID- 25764623
TI  - Dengue: a global threat.
AB  - Dengue, a mosquito-borne viral disease, is currently an expanding global problem.
      The disease is caused by four closely related dengue serotypes; it ranges from
      asymptomatic infection to undifferentiated fever, dengue fever (DF) and dengue
      hemorrhagic fever (DHF). DHF is characterized by fever, bleeding diathesis and a
      tendency to develop apotentially fatal shock syndrome. Dengue infection with
      organ impairment mainly involves the central nervous system and liver. Consistent
      hematological findings include vasculopathy, coagulopathy and thrombocytopenia.
      Laboratory diagnoses include virus isolation, serology, and detection ofdengue
      ribonucleic acid. Successful treatment, which is mainly supportive, depends on
      early recognition of the disease and careful monitoring for shock. A severity
      based revised dengue classification for medical interventions has been developed
      and validated in many countries. So far however, there has not been any specific
      dengue treatment; prevention is currently limited to vector control measures. The
      world's first, large-scale dengue vaccine, efficacy study demonstrated its
      efficacy and a reduction of dengue's severity in a study of more than 10,000
      volunteers in Asia. Initial safety data are consistent with a good safety
      profile.

PMID- 25764624
TI  - Conceptive options for people living with HIV.
AB  - Seroconcordant and serodiscordant couples living with HIV should be counseled and
      informed regarding reproductive health issues, including conceptive options.
      Assisted conception, sperm washing, timed intercourse, and vaginal self
      insemination are options to be considered by HIV-affected couples who wish to
      conceive with a lowered risk of viral transmission. Pre-exposure prophylaxis may
      be an adjunctive method to reduce the risk, particularly among serodiscordant
      couples.

PMID- 25764625
TI  - Orthotopic liver transplantation at King Chulalongkorn Memorial Hospital: a
      report.
AB  - Orthotopic liver transplantation (LT) is the treatment of choice for various
      liver diseases including early hepatocellular carcinoma (HCC). After the first
      successful LT in Thailand at King Chulalongkorn Memorial Hospital (KCMH) in 1987,
      the number of LT has gradually been increasing in parallel with the improvement
      in patient survival. The recent outcomes of LT are reported herein. From January
      1, 2002 to June 30, 2013, 120 cases of adult LT and 24 cases of pediatric LT were
      performed. The most common indication for LT was HCC in the adult whereas biliary
      atresia was the most common indication for LT in pediatric patients. As for the
      severity of liver disease, the average model of end stage liver disease (MELD)
      and pediatric end stage liver disease (PELD) scores were 19 in adult LT and 21.5
      in pediatric LT respectively. The most common perioperative complication in adult
      LT was acute renal failure (25%). One-, five-year patient survival in adult LT
      and pediatric LT were 85%, 69% and 96%, 91%, respectively. In conclusion, the
      outcomes of LT at KCMH have gradually been improving close to the world standard,
      especially the patient survival.

PMID- 25764626
TI  - Characteristics and health consequences of adolescent sexual assault at Police
      General Hospital, Thailand.
AB  - OBJECTIVE: To describe the characteristic and epidemiology ofadolescent sexual
      assaults and to compare health consequences between adolescent and adult victims.
      MATERIAL AND METHOD: Retrospective review of sexual assault victims records of
      those who were examined in sexual assault program in Police General Hospital
      between January 1 and December 31, 2012. RESULTS: There were 335 cases
      ofadolescents sexual assault victims. Most of them were in junior high school
      (62.4%). Most adolescent sexual assaults were committed by boyfriends (50.3%) and
      acquaintance/friends (14.7%). The most common place for the assaults was the
      offender's residence (52.9%). Delayed medical evaluation was common. Only 49.4%
      attended medical evaluation within 72 hours. Adolescent victims had a higher
      pregnancy rate than adult victims (9.0% vs. 3.6%), but lower rate of non-genital
      injuries (14.6% vs. 36.3%). Only labia minora injury of adolescent was
      significantly lower than adult (9.3% vs. 17.5%) among genital injuries. Hepatitis
      B infection rate of adolescent was lower than adult (1.2% vs. 4.5%), whereas
      other types of infection were not different. CONCLUSION: Thai adolescents had set
      the unique assault characteristic different from adult victims. Adolescent
      victims were mainly assaulted by boyfriends at assailant's residence, with higher
      pregnancy rate than other international reports. Promote education to
      adolescences is highly recommended to decrease cases of rape and rape-related
      pregnancy in female adolescent.

PMID- 25764627
TI  - Physical health consequences of child sexual assault in Police General Hospital.
AB  - OBJECTIVE: To determine demographic data and physical health consequences of
      Child Sexual Assault (CSA) victims at the Police General Hospital (PGH). MATERIAL
      AND METHOD: The medical records of CSA age one to 12 years at PGH between January
      1, 2012 and December 31, 2012 were retrospectively reviewed. RESULTS: Of 124
      child victims, 120 (96.8%) were female andfour (3.2%) were male, aged between one
      and 12 years (mean, 8.12 +/- 3.54 years). Most of assailants were acquaintance or
      boyfriend The majority of victims had no body injury, 114 (91.9%). Genital
      injuries offemale victims were found in 40.8% of the cases and commonly seen at
      hymen. Anal injury was found in one case. Sexual transmitted infections included
      gonococcal 12.9%, chlamydial 4.0%, and trichomanas 1.7% were found. Two pregnancy
      cases were found. CONCLUSION: Most of CSA had no physical injury. None of the
      injury cases required any suture or hospital admission. Majority of sexual injury
      was new hymenal tear.

PMID- 25764628
TI  - Clinical manifestation, diagnosis, management, and treatment outcome of
      pericarditis in patients with systemic lupus erythematosus.
AB  - OBJECTIVE: To investigate the clinical manifestations, diagnosis, etiology,
      management, and outcomes of patients with systemic lupus erythematosus (SLE) and
      pericarditis MATERIAL AND METHOD: The authors retrospectively reviewed the
      records of 81 patients who were diagnosed of SLE according to the American
      College of Rheumatology criteria and had 82 episodes of pericarditis between 2002
      and 2010. The diagnosis of pericarditis was defined as the presence of
      pericardial effusion alone by echocardiography or having 2 out of 4 of the
      following criteria: retrosternal pain, pericardial friction rub, widespread ST
      segment elevation, and new/worsening pericardial effusion. RESULTS: Most of them
      (92%) were female with the median disease duration (range) of 1 (0-312) month.
      Cardiac tamponade occurred in 16% (95% CI 8.72-25.58%). There was no
      statistically significant difference between patients who developed tamponade and
      those who did not. The causes ofpericarditis included active SLE (93%), and
      suspected tuberculosis (TB) (5%), with 2% inconclusive. In patients with lupus
      pericarditis, 71% had other active organ involvement. Most lupus pericarditis
      patients (79%) had good response to steroid or NSAIDs. Diagnosis of TB
      pericarditis was made by clinical suspicion without microbiological or
      pathological evidence. CONCLUSION: In an endemic area of TB, lupus pericarditis
      was still the most common cause of pericarditis in SLE. Most patients responded
      well to steroid.

PMID- 25764629
TI  - Effectiveness of direct observation and supervision at out-patient setting on
      improving clinical skills of medical students.
AB  - BACKGROUND: Direct observation and supervision (DOS) is the teaching method where
      a mentor provides direct observation during patient encounter and provides
      feedback to the learner in real-time manner Previous studies showed that DOS
      improves patient care and trainees' clinical skill but is difficult to implement.
      OBJECTIVE: To evaluate students' performance and attitude after implementing DOS
      to the 5th year medical students. MATERIAL AND METHOD: DOS was introduced for the
      whole class of the 5th year medical students throughout the year at out-patient
      setting department of Medicine, Siriraj Hospital in 2012. DOS sessions were
      provided during the first few patients 'encounters. Students 'performances at out
      patients clinics were ratedfor other 8 subsequence sessions. The average score
      were compared to the 5th year medical students in 2011 (Conventional technique,
      CT). RESULTS: Two hundred andforty six students were supervised in DOS group. The
      mean score ofstudents who received DOS was significantly higher than CT group
      with the score of 8.2 compared to 7.9, respectively (p < 0.001). With respect to
      students'satisfaction, 75% of students rated DOS as a learning method with high
      to very high benefit. CONCLUSION: DOS method is feasible to implement and could
      improve student's performance with good satisfaction from medical students.

PMID- 25764630
TI  - First medical contact to device time in the Thailand percutaneous coronary
      intervention (PCI) registry.
AB  - OBJECTIVE: The aim of this study is to evaluate the first medical contact (FMC)
      to device time in the Thai national PCI registry 2006, and its effect on the
      clinical outcome. MATERIAL AND METHOD: Thailand national PCI registry enrolled
      4,156 patients who underwent PCI from the all catheterization laboratories in
      Thailand between May 1st and October 31st, 2006. RESULTS: 581 patients with acute
      myocardial infarction (AMI), 352 patients underwent primary angioplasty, 229
      patients underwent rescue angioplasty/facilitated PCI or after successful
      thrombolytic. Median FMC.to device time in primary angioplasty group was 115
      minutes (range 24-1335 minutes); only 29.8% of patients who able to achieve FMC
      to device time <= 90 minutes. Cardiogenic shock was significant lower if FMC to
      device time <= 90 minutes (2.1% (1/48) versus 12.4% (14/113) if FMC to device
      time > 90, p = 0.040). In-hospital mortality occurred for 4.8% (2/48) ifFMC to
      device time <= 90 minutes and was 8.8% (10/113) if FMC to device time > 90
      minutes, p = 0.510). Death occurred in 4.2% (2/48) if FMC to device time <= 90
      minutes, 6.3% (5/79) if FMC to device time between 91-180 minutes, 6.7% (1/15) if
      FMC to device time between 181-270 minutes, 42.9% (3/7) if FMC to device time
      between 271-360 minutes and 8.3% (1/12) if FMC to device time > 360 minutes, (p =
      0.040). CONCLUSION: FMC to device time is strongly associated with the risk
      ofcardiogenic shock and mortality. In Thailand national PCI registry in 2006, the
      majority of the patients did not receive primary PCI in timely fashion.

PMID- 25764631
TI  - In vitro activity of polymyxin B against carbapenem-resistant Acinetobacter
      baumannii.
AB  - OBJECTIVE: To determine in vitro activity of polymyxin B against carbapenem
      resistant Acinetobacter baumannii. MATERIAL AND METHOD: The activity of polymyxin
      B was determined against 217 strains of carbapenem-resistant A. baumannii
      collected from different patients by standard agar dilution method and disk
      diffusion test using polymyxin B disk (300 units). The control strains were E.
      coli ATCC 25922 and P. aeruginosa ATCC 27853. RESULTS: The MIC values and
      inhibition zone diameters of polymyxin B against the quality control bacteria
      were within the acceptable range. The MIC50 and MIC90 values of polymyxin B
      against 217 strains of carbapenem-resistant A. baumannii were 0.5 and 1 mg/l,
      respectively. If the susceptible MIC breakpoint of polymyxin B was <= 2 mg/l,
      98.2% of carbapenem-resistant A. baumannii strains were susceptible to polymyxin
      B. If the susceptible MIC breakpoint of polymyxin B was <= 2 mg/l, the
      sensitivity and the specificity ofthe inhibition zone diameter of > 12 mm were
      100% and 75%, respectively. The aforementioned diagnostic parameters gave
      positive predictive value of 99.5% and negative predictive value of 100% for
      predicting susceptibility of carbapenem-resistant A. baumannii to polymyxin B by
      disk diffusion test. CONCLUSION: Polymyxin B was very active against carbapenem
      resistant A. baumannii. The inhibition zone diameters of >12 mm was accurate
      enough to determine susceptibility of carbapenem-resistant A. baumannii
      topolymyxin B. Polymyxin B can be an alternative to or more preferable than
      colistin for therapy ofcarbapenem-resistant A. baumannii infections.

PMID- 25764632
TI  - In vitro and in vivo activity of tebipenem against ESBL-producing E. coli.
AB  - OBJECTIVE: To determine in vitro and in vivo activity of tebipenem against ESBL
      producing E. coli. MATERIAL AND METHOD: Minimum inhibitory concentration (MIC) of
      tebipenem against 100 clinical isolates of ESBL-producing E. coli was performed
      by broth micro-dilution technique. Blood and urine samples from 10 healthy male
      subjects before and after receiving 300 mg of tebipenem pivoxil 3 times a day for
      2 consecutive days were determined for inhibitory and bactericidal titers against
      a clinical urinary isolate of ESBL-producing E. coli by disk diffusion method and
      broth micro- dilution method. RESULTS: MIC50 and MC90 of tebipenem against ESBL
      producing E. coli were both 0.06 mg/L with MIC range from <= 0.06 to 0.25 mg/L.
      The inhibition zones were observed around the disks inoculated with serum samples
      and urine samples collected from all study subjects after receiving tebipenem
      pivoxil for at least 1 hour and 5 hours, respectively. The inhibitory titer of
      1:160 and bactericidal titer of 1:160 of serum samples were observed for at least
      one hour after ingestion of tebipenem pivoxil. Inhibitory titer of 1:640 and
      bactericidal titer of 1:640 of urine samples were observed after at least 14
      hours after ingestion of tebipenem pivoxil. No subjects experienced side effects
      related to receiving tebipenem pivoxil. CONCLUSION: Tebipenem is very active
      against ESBL-producing E. coli. Oral administration of tebipenem pivoxil 300 mg 3
      times a day for two days was well tolerated, safe and induced high inhibitory and
      bactericidal activity in serum and urine. Tebipenem pivoxil could be an oral
      agent for effective therapy of ESBL-producing E. coli infections.

PMID- 25764633
TI  - Learning environment and resident achievement.
AB  - OBJECTIVE: To evaluate the effect of program training atmosphere on the academic
      performance among internal medicine residents. MATERIAL AND METHOD: Data of
      satisfaction survey among internal medicine residents in academic year 2012,
      conducted by the Royal College of Physicians of Thailand, were retrieved.
      Association between training environment rating scores in three major aspects
      (program training structure, faculty nurturance, and support system) and board
      certifying examination scores, were then assessed. RESULTS: There were 12
      training centers with 535 residents in that academic year. The mean satisfaction
      score for second-year residents was 77.1 +/- 6.1, and the mean written
      examination score was 56.4 +/- 4.6, with the modest correlation (r = 0.515, p =
      0.087). For the third-year residents, the mean satisfaction score was 78.5 +/-
      6.5 and the mean clinical examination score was 71.1 +/- 1.6, with no correlation
      (r = -0.004, p = 0.991). In the subgroup analysis in second-year residents,
      program training structure had strongest influence (r = 0.569, p = 0.053), as
      compared to faculty nurturance (r = 0.425, p = 0.169), andsupport system (r =
      0.492, p = 0.104). CONCLUSION: Perception of positive training environment,
      especially the program training structure, may influence the performance of
      internal medicine residents in term of knowledge achievement as determined by
      written examination score. However, it has no effect in terms of clinical skill
      accomplishments, as determined by clinical examination scores.

PMID- 25764634
TI  - Optimal INR level in Thai atrial fibrillation patients who were receiving
      warfarin for stroke prevention in Thailand.
AB  - OBJECTIVE: To determine the optimal International Normalized Ratio (INR) level in
      Thai atrialfibrillation (AF) patients who received warfarin. MATERIAL AND METHOD:
      This retrospective study enrolled 230 AF patients that received warfarin in
      Siriraj Hospital between January 1, 2005 andDecember 31, 2009 and collected the
      INR level at the time of the event, the numbers of ischemic stroke, and bleeding
      events. The incidence density of ischemic stroke or bleeding events was
      calculated by dividing the number of ischemic stroke or bleeding event in each
      INR level with the summation of the time that each patient stayed in each INR
      group. The patients with a prosthetic valve were excluded. The INR range was
      classified into six groups (less than 1.5, 1.5 to 1.9, 2.0 to 2.4, 2.5 to 2.9,
      3.0 to 3.4, and greater than 3.4). The optimal INR level was defined as the
      lowest incidence density of ischemic stroke and bleeding complications. RESULTS:
      Two hundred thirty AF patients (the mean age 68 +/- 12 years) were enrolled,
      contributing to 737.54 patient-years of observation period. Of the 230 patients,
      nine patients experienced 12 ischemic events (1.6 per 100 patient-years) and 54
      patients experienced 57 bleeding events (7.7 per 100 patient-years). The
      percentage of patient-time spent within INR 2 to 3, INR less than 2, and INR more
      than 3 were 40.75, 46.22, and 13.03%, respectively. The INR level more than 3.4
      increased both major and minor bleeding events (p = 0.001). The INR level of 3.0
      to 3.4 increased the minor bleeding events (p = 0.03). The INR level less than
      1.5 increased incidence of ischemic stroke (p = 0.03). The overall event rate was
      lowest in the INR range from 1.5 to 2.9, which is significantly different from
      that of lNR more than 2.9 (p < 0.0001), but trend lower than INR less than 1.5
      without being statistically significant (p = 0.198). CONCLUSION: An INR of 1.5
      2.9 appeared to be associated with the lowest incidence rate of bleeding or
      ischemic stroke in a cohort of Thai AFpatients receiving warfarin therapy for
      stroke prevention.

PMID- 25764635
TI  - Prescribing rate of influenza vaccine among internal medicine residents for
      outpatient continuum care.
AB  - BACKGROUND: Annual epidemics of influenza viruses remain a substantial cause of
      morbidity and mortality worldwide particularly among vulnerable groups.
      Immunization is another way to reduce the infection and mortality rates,
      especially in high-risk groups; however the data concerning prescription rates
      and possible influencing factors on decisions associated with influenza
      prescription of Thai internal medicine residents were limited OBJECTIVE: Siriraj
      internal medicine residency training has provided outpatient continuum care
      practice for all 1st year residents since 2008. A part of the curriculum was to
      prepare each trainee to be an effective vaccinator. This study aims to examine
      the competency ofthose residents who had completed the training, particularly
      about prescribing influenza vaccine. MATERIAL AND METHOD: The authors
      retrospectively reviewed medical records of the patients that indicated need for
      influenza vaccine encountered by 2nd and 3rd year residents during June 2011 and
      May 2012. The 20-item questionnaire was also sent out in order to study possible
      factors associated on prescribing the vaccine. RESULTS: Three hundred and seventy
      three medical records were included and reviewed. The prescription rate of
      influenza vaccine was 8.0 percent. Comparing vaccine receiving and non-receiving
      groups, the authors found having respiratory problems (26.7% vs. 4.4%; odds ratio
      8.0 [3.0-20.8]; p < 0.001) and being self-paying (16.7% vs. 5.8%; odds ratio 3.2
      [1.1-9.3]; p = 0.023) were the only two significant differences. Only 5.7 percent
      of total residents were an effective vaccinator One hundred and five residents
      returned the questionnaire. Residents who had further plans for fellowship
      trainings had reported a higher influenza vaccine prescription rate than those
      who will be general internists (45.2% vs. 8.1%; adjusted odds ratio 14.04 [1.6
      125.8]; p = 0.018). The authors also found that the rate of vaccine recognition,
      general knowledge of vaccination, and vaccine coverage remained 61.9%, 29.5%, and
      21.0% among medicine residents. CONCLUSION: Prescribing rate of influenza vaccine
      remained low due to multifactor aspects, including doctor capability, attitude,
      patient recognition as well as reimbursement issues. In order to improve the rate
      of influenza vaccine prescriptions, a system-designed approach would be needed.

PMID- 25764636
TI  - Relationship between emphysema quantification and COPD severity.
AB  - OBJECTIVE: To determine the association between emphysema extent from high
      resolution computed tomography (HRCT) and the physiological derangement in
      patients with chronic obstructive pulmonary disease (COPD). MATERIAL AND METHOD:
      A cross-sectional study was undertaken to quantify the emphysema severity in 23
      COPD patients by automated HRCT scoring techniques. Correlation with phenotypic
      characters in term of exercise capacity [Modified Medical Research Council (mMRC)
      dyspnea scale, and 6-minute walk distance (6MWD)], pulmonary function testing
      [spirometry (forced expiratory volume in 1 second, FEV1 and forced vital
      capacity, FVC), and diffusing capacity (DLCO)], were then assessed. RESULTS:
      Nineteen patients were male and four were female, the mean age was 73 +/- 8
      years, with the mean FEV1 % predicted of 67.8 +/- 25.4. Percentage of inspiratory
      emphysematous lung volume (%ELVi) had significant negative correlation with
      %FEV/FVC (r = -0.50, p = 0.016) and DLCO (r = 0.58, p = 0.011). Percentage of
      expiratory emphysematous lung volumes (%ELVe) also had the same correlation with
      %FEV/FVC (r = -0.58, p = 0.004) and DLCO (r = 0.48, p = 0.042). In addition,
      %ELVe also had significant negative correlation with 6MWD (r = 0.50, p = 0.016),
      but had significant positive correlation with mMRC scale (r = 0.53, p = 0.01).
      CONCLUSION: Severity of emphysema assessed by HRCT was well correlated with
      pulmonary function test results and exercise capacity. It can be used as one
      aspect ofphenotypic characters in patients with COPD,for designing personalize
      management plan.

PMID- 25764637
TI  - Utilization of flow cytometry for diagnosis of hematologic malignancies in
      Thailand: increasing trends and diagnostic yields in 7,982 samples.
AB  - BACKGROUND: Diagnosis of hematologic malignancies requires a multidisciplinary
      approach. Flow cytometry (FCM) has become an essential tool for immunophenotypic
      studies of malignant hematopoietic cells. OBJECTIVE: To evaluate the utilization
      trend of FCM and its diagnostic yields for hematologic malignancy at a major
      teaching hospital in Thailand. MATERIAL AND METHOD: FCM results of bone marrow
      (BM) and peripheral blood (PB) specimens during 2000-2013 were analyzed and
      compared to clinical diagnosis. RESULTS: Overall, 7,982 specimens were submitted
      for diagnostic FCM including 6,561 BM and 1,421 PB. The number of specimens
      analyzedwas 121, 142, 164, 299, 491, 431, 690, 611, 719, 744, 725, 863, 955 and
      1,027, respectively, from 2000 to 2013. The most common clinical diagnoses
      requested for FCM were acute leukemia (5,911 cases, 74%) followed by lymphoma
      (1,419 cases, 17.8%), and chronic lymphocytic leukemia (CLL) (634 cases, 7.94%).
      The highest diagnostic yield of FCM was found in acute leukemia cases (69.71%)
      followed by CLL (35.33%). Only 15.43% of clinically suspected lymphoma cases were
      positive by FCM. Overutilization of PB (35.6% of cases) instead of BM for
      lymphoma staging significantly contributed to low diagnostic yields of lymphoma
      by FCM as circulating tumor cells may not be present in such cases. CONCLUSION:
      FCM has an increasing role in the diagnosis of hematologic malignancies in Thai
      patients over the past 14 years with the highest diagnostic yield in acute
      leukemia. Appropriate specimen types and study indications are required in order
      to reduce futility of costly diagnostic tests and improve diagnostic yields.

PMID- 25764638
TI  - Comparison of blood loss between using non central part cutting knee prosthesis
      and distal central part cutting.
AB  - BACKGROUND: Patients who undergo knee replacement surgery may need to receive a
      blood transfusion due to blood loss during the operation. Therefore it was
      important to improve the design of knee implant operative procedures in an
      attempt to reduce the rate of blood loss. OBJECTIVE: The present study aimed to
      compare the blood loss between two types of knee replacement surgery. MATERIAL
      AND METHOD: This is a retrospective study in which 78 patients received cemented
      knee replacements in Phayao Hospital between October 2010 and March 2012. There
      were two types of surgical procedure: 1) using an implant position covering the
      end of the femoral bone without cutting into the central part of the distal
      femoral, 2) using an implant position covering the end of the femoral bone
      cutting the central part of the distal femoral. Blood loss, blood transfusion,
      hemoglobin and hematocrit were recorded preoperatively, immediately postsurgery
      and 48 hours after surgery. RESULTS: Findings revealed that the knee replacement
      surgery using the implant position covering the end of the femoral bone without
      cutting the central part of the distal femoral significantly lowered the rate of
      blood loss when compared to using the implant position covering the end of the
      femoral bone with central cutting of the distal femor. The average blood loss
      during the operation without cutting at the central part of distal femoral was
      49.50 +/- 11.11 mL; whereas the operation cutting the central part of the distal
      femoral was 58.50 +/- 11.69 mL. CONCLUSION: As regards blood loss, the knee
      replacement surgery using the implant position covering the end ofthefemoral bone
      without cutting the central part of distal femor was better than using the
      implant position covering the end of the femoral bone cutting at the central part
      of the distal femor.

PMID- 25764639
TI  - Correlation of intraoperative anthropometric measurement of resected Thai distal
      femurs between unisex and gender-specific implants.
AB  - OBJECTIVE: To measure the intraoperative anthropometric dimensions of Thai distal
      femurs in order to correlate that data with unisex and gender-specific TKR
      implants, and to analyze the suitability of gender-specific prostheses for Thai
      female knees. MATERIAL AND METHOD: Two hundred Thai patients (170 females and 30
      males) who underwent unilateral TKR were recruited. Three parameters of resected
      distal femurs were measured intraoperatively including anteroposterior dimensions
      of medial (APM) and lateral (APL) condyles, and mediolateral (ML) width of total
      condyles which were compared with the dimensional data of two femoral implant
      components, Nexgen LPS-Flex and Gender Solution Nexgen LPS-Flex. Scatter diagrams
      were used to assess compatibility; the final type and size of implanted
      prostheses were recorded. RESULTS: Thai females had significantly smaller knees
      than Thai males. The femoral components of both types of prostheses were found to
      have a tendency toward ML under-coverage in both female and male femurs. These
      mismatches were more noticeable when small-sized, gender-specific prostheses were
      used. The overall rate of use of gender-specific components in this study was
      15%. CONCLUSION: The unisex and gender-specific prostheses evaluated in this
      study do not appear suitable for Thai knees. Particular modifications of implants
      are required for Thai knees.

PMID- 25764640
TI  - Femoral mechanical-anatomical angle of osteoarthritic knees.
AB  - BACKGROUND: To perform total knee arthroplasty, some surgeons prefer to use a
      fixed valgus angle, for example 5 degrees  or 6 degrees , for the distal femoral
      cut with every patient. This angle may be appropriate for some patients, but may
      not be for all. OBJECTIVE: To determine the proper angle of the distal femoral
      cut during total knee arthroplasty (TKA) in Thai patients with osteoarthritis of
      the knee. MATERIAL AND METHOD: A cross-sectional study was conducted of 80
      osteoarthritic knees of 50 Thai patients with a mean age of 69 years (range 52
      82, SD 7.64) who had received total knee arthroplasty at Chiang Mai University
      Hospital between January 2011 and March 2013. The femoral mechanical-anatomical
      (FMA) angle, femorotibial (FT) angle, mechanical femorotibial (MFT) angle,
      femoral bowing angle, femoral length, hip offset, gender, and age of the patients
      were analysed using multivariate regression analysis. RESULTS: Average FMA angle
      was 6.46 degrees  (range 4 degrees -10 degrees , SD 1.26 degrees ). The FMA angle
      was 6.85 degrees  and 5.28 degrees  in patients with varus and valgus deformity,
      respectively. Fifteen percent of all patients showed a FMA angle either less than
      5 degrees  or greater than 7 degrees . CONCLUSION: The average FMA angle of
      patients with gonarthrosis was 6.46 degrees . If it is not possible to measure
      the FMA angle in Thai patients, 7 degrees  valgus cut angle is recommended for
      patients with varus deformity. Variation in this angle was high. Pre-operative
      measurement of FMA angle is beneficial for precise TKA.

PMID- 25764641
TI  - Off-loading total contact cast in combination with hydrogel and foam dressing for
      management of diabetic plantar ulcer of the foot.
AB  - BACKGROUND: The total contact cast is considered to be an effective method of off
      loading a diabetic non-infected pressure ulcer. However complications have been
      reported in 1 to 15% of cases, e.g. prolonged healing of the ulcer. Debridement
      with modern dressings has been reported to be effective in promoting wound
      healing; however there have been few reported studies of the combination of
      modern dressings with the cast. OBJECTIVE: To evaluate the effectiveness of a
      combination of treatments on healing rates in diabetic non-infected plantar ulcer
      of the foot. MATERIAL AND METHOD: This retrospective study with prospective data
      collection was conducted between September 2010 and August 2012. Twenty diabetic
      patients with plantar neuropathic ulcer were treated using a combination of a
      contact cast plus hydrogel andfoam dressings. The size and location of the ulcer,
      ulcer healing, foot deformities and complications were evaluated. RESULTS: Of 21
      ulcers, 20 (95.2%) healed completely in a mean time of 30.1 days (range 14 to 70
      days). Healing times for forefoot and midfoot ulcers were 22.6 and 26.8 days,
      respectively, which is significantly shorter than the 51.7 days for heel ulcers.
      One patient who had an unhealed ulcer developed a severe infection two months
      after treatment, which necessitated below the knee amputation. There were three
      cases of recurrence of the ulcers after casting. CONCLUSION: Off-loading casting
      combined with modern dressings had a high rate of healing in short-term treatment
      of diabetic non-infected pressure ulcers. Recurrence of ulcers and new site
      abrasions were common complications; those complications may have been caused by
      association with bone deformity or improper footwear.

PMID- 25764642
TI  - Open biological reduction and a locking compression plate for distal femoral
      fractures: a review of 40 cases.
AB  - OBJECTIVE: To determine the clinical results of patients with comminuted
      fractures of the distal femur treated by open biological reduction using an
      indirect reduction technique and locking compression plate (LCP) without primary
      bone grafting. MATERIAL AND METHOD: Prospective observation was conducted with 40
      patients (24 males and 16 females), average age 48.7 years (range 20-81), with
      distal femoral fractures AO/OTA types A2 (5), A3 (17), C2 (8) and C3 (10) who
      were treated using an open indirect reduction technique and fixation with LCP
      between May 2010 and December 2013. Among the 40 patients, 28 were closed
      fractures and 12 were open fractures. Clinical results were evaluated using the
      Neer score six months after surgery. Follow-up periods ranged from 12 to 36
      months (average 18.35). RESULTS: Thirty eight (95%) of the fractures healed
      completely without a secondary procedure. The average time to union was 14.45
      weeks (range 12-24). The average knee range of motion was 2 degrees  (0-5) to 110
      degrees  (20-140). Two patients had an implant failure which required revision
      and secondary iliac bone grafting. There were no varus or valgus deformities, no
      limb shortening and no deep infections. Neer scores were excellent in 18 cases
      (45%), good in 14 (35%), fair in 6 (15%) and poor in 2 (5%). The mean Neer score
      was 83.60 (range 50-100). CONCLUSION: The indirect reduction technique for the
      treatment of comminuted distal femoral fractures provides satisfactory results
      when combined with LCP fixation.

PMID- 25764643
TI  - Post-op pain and blood loss in total knee arthroplasty: an RCT using
      periarticular injection with diclofenac-based multimodal drugs.
AB  - OBJECTIVE: To study post-operative pain and blood loss after intraoperative
      periarticular injection with the multimodal drugs diclofenac, adrenaline,
      marcaine (bupivacaine) and morphine in total knee arthroplasty. MATERIAL AND
      METHOD: A prospective randomized controlled trial of knee osteoarthritis patients
      age more than 55 years undergoing total knee arthroplasty at Maharat Nakhon
      Ratchasima hospital from January 2011 through June 2012 was performed. A group
      receiving intra-operative periarticular injections was compared to a control
      group receiving no injections. Half of a group of forty-two patients, 2 males and
      40 females, average age 67.9 years (range 57-84 years), were randomly assigned to
      receive the periarticular injection (the injection group), the others to the
      control group. Pain was measured by two methods: visual analog score at 6, 12, 24
      and 48 hours post-operation and by patient controlled analgesia (PCA) measuring
      the daily amount of intravenous morphine used. The amount of blood loss post
      operation (in the redivac drain), degree of knee flexion, time to onset of
      assisted ambulation, length of hospital stay and any complications were also
      analyzed. RESULTS: The mean VAS at 6 and 12 hours post operation of the injection
      group were 2.67 and 2.48, whereas the values for the control group were 6.10 and
      4.95, respectively (p < 0.05). Mean quantities of morphine used by PCA by the
      injection group during the first day was 9.43 mg, significantly lower than the
      18.81 mg used by the control group. Average blood loss of the injection group at
      263.8 ml was also significantly below the 362.1 ml of the control group (p <
      0.05). The degree of knee flexion, time to onset of assist ambulation, length of
      hospital stay and complications, however were not significantly different between
      the groups. CONCLUSION: Multimodal drugs, periarticular injections consisting of
      diclofenac, adrenaline, Marcaine plus a patient controled anesthetic machine
      (PCA) with morphine can significantly reduce post-operative pain and blood loss
      in total knee arthroplasty without significant adverse effects.

PMID- 25764644
TI  - Prevalence of fall in patients with total knee arthroplasty living in the
      community.
AB  - BACKGROUND: Knee osteoarthritis (OA) with pain, stiffness and functional
      limitations is associated with risk of falls. Total knee arthroplasty (TKA) is an
      effective treatment for OA knee and affords significant improvements in pain,
      function and proprioception. Many studies have shown proprioceptive/balance
      deficits and decreases in knee extension strength following TKA, which could
      increase risk of falls. OBJECTIVE: To identify the prevalence rate andfall-risk
      in Thai TKA patients. MATERIAL AND METHOD: A cross-sectional study was conducted
      among patients with TKA diagnosed with primary OA who living in the community.
      RESULTS: There were 54 patients (46 females, 8 males). Mean time between surgery
      and interview was 38.9 +/- 16.6 (7-73) months. The one-year prevalence of falls
      among patients was 42.6% (23/54 patients): total frequency was 34 times (1-4
      times/case). Three fallers needed treatment: one by open reduction and internal
      fixation with plate and screws of periprosthetic fracture of the femur, and the
      others needed hospitalization due to hemathrosis of non-TKA knees. The WOMAC pain
      and stiffness scores were significantly higher in the faller group than the non
      faller group. Limitation of joint motion was the main fall-risk factor (OR 6.3;
      95% CI 1-67.2, p < 0.05). CONCLUSION: The prevalence rate offalls for this group
      of TKA patients was about 42%. Limited motion and pain of the knee joint were
      associated with falls in this study group.

PMID- 25764645
TI  - Safety entry point, size and direction for placement of thoracic pedicle screw--a
      cadaveric study.
AB  - BACKGROUND: Understanding of the pedicle anatomy is necessary for pedicle screw
      placement; however, there have been few Thai studies reporting on thoracic
      pedicle morphometry. OBJECTIVE: To determine important anatomical measurements
      for thoracic pedicle screw fixation. MATERIAL AND METHOD: T1-T12 vertebral
      pedicles were evaluated in 27 cadavers. The diameter angle, length and entry
      point of the pedicle were measured. RESULTS: The transverse diameter was smaller
      than the sagittal diameter at all levels. The narrowest transverse diameter was
      at the T5 level in males and T4 level in females. The pedicle diameter in males
      was statistically significantly greater than in females at all levels except at
      the T12 level. Most pedicles with a transverse diameter of 5.0 mm or less were
      found at the T4, T5, T6 and T7 levels. The transverse angle was widest at the T1
      level; it faced medially at all levels. The sagittal angle was widest at the T12
      level andfaced cephaladly at all levels. The axis length was shortest at the T1
      level. Most entry points were at the inferolateral zone. CONCLUSION: A 4-mm
      diameter screw should be used carefully at the mid-thoracic levels for Thai
      people, especially females. Screw lengths of less than 30 mm are safe for
      placement at all levels. The safe zone for the pedicle entry point is in the
      inferolateral zone.

PMID- 25764646
TI  - Cadaveric study of superficial palmar arch variations in northern Thai population
      by using epoxy resin injection technique.
AB  - BACKGROUND: Superficial palmer arch (SPA) is the main source of arterial supply
      to the palm whileprincepspollicis artery is the main source of arterial supply to
      the thumb. The details about their possible variations are important for the
      reconstructive hand surgeons. OBJECTIVE: To find out the SPA patterns and
      arterial supply of thumb variations in Thai population by using epoxy resin
      injection technique. MATERIAL AND METHOD: The methods used were vascular
      injection by epoxy resin with blue resin color to brachial artery before
      dissection of 100 fresh cadaveric hands to find out the SPA pattern and the
      anatomical variation of the princeps pollicis artery. RESULTS: It was found that
      the SPA patterns of 100 cadaveric hands were composed of 13 patterns, which could
      be classified into two main types: arch type and non-arch type. Arch type was
      found in 67 hands (67%) and non-arch type 33 hands (33%). From 13 patterns, the
      most common was the ulnar + 1st dorsal interosseous pattern, which found in 27
      hands (27%) and the less common, in 15 hands was ulnar pattern in both arch type
      and non-arch type. The princeps pollicis artery was present in all of the arch
      type hands (67 hands) with its origin from the radial artery. It emerged deep in
      the 1st dorsal interosseous muscle in 66 hands (98.5%) and dorsally to this
      muscle in 1 hand (1.5%). Using epoxy resin injection before dissection was a good
      technique with less confusion for arteries and other tissues. CONCLUSION: The
      authors found 13 superficial palmar arch patterns, 67 percent is arch type. The
      princeps pollicis artery always lies deep in the first dorsal interosseous
      muscle. This is essential knowledge for the hand surgeon to repair or reconstruct
      the injured limb.

PMID- 25764647
TI  - Fungal periprosthetic joint infection after total knee arthroplasty.
AB  - Total knee replacement is an effective procedure for severely diseased knee
      joints; however one of the major problems resulting in failure of arthroplasty is
      periprosthetic joint infection. Fungal infection is rarely found perprosthetic
      joints infection, but the incidence may be increased in high riskpatients.
      Progression of the disease and definitive treatment guidelines have not yet been
      established. In two cases of fungal periprosthetic joint infection the organism
      was identified from cultures as Candida spp. Those patients had developed
      symptoms of pain and local knee inflammation six years after total knee
      replacement. A two-stage operation was carried out. The first operation removed
      the prosthesis, the polyethylene surface, the cement mantle and the infected
      tissue. After identification of the organism, the correct antibiotic was
      administered until the infection was controlled. A second operation was carried
      out to re-implant the prosthesis after the infection had subsided. A summary of
      reports in the literature regarding treatment of fungal periprosthetic infections
      as well as an algorithm for treatment decision making are presented.

PMID- 25764648
TI  - Rare manifestations of Streptococcus pneumoniae infection; the first case report
      in Thailand and literature review of pneumococcal endophthalmitis and
      endocarditis.
AB  - We report a case of endogenous endophthalmitis and endocarditis caused by a rare
      causative organism: Streptococcus pneumoniae. A 69-year-old woman with diabetes
      mellitus and pre-existing mitral regurgitation presented with acute fever and
      severe left eye pain. Ophthalmologic examination revealed bilateral
      endophthalmitis. Blood and vitreous fluid culture grew penicillin-susceptible S.
      pneumoniae. Transesophageal echocardiogram documented a 5-mm oscillating mass at
      right coronary cusp of aortic valve. After 4 weeks of combined ceftriaxone and
      levofloxacin therapy, the patient improved and was later discharged with
      blindness in her left eye.

PMID- 25764649
TI  - [Application of three-way data analysis (second-order tensor decomposition)
      algorithms in analysis of liquid chromatography].
AB  - Using dropline separation, tangent skimming, and triangulation to estimate the
      area of an overlapping chromatographic peak might contribute to a large
      deviation. It is easy, however, to eliminate these errors caused by geometric
      segmentation using three-way data analysis (second-order tensor decomposition)
      algorithms. This method of chromatographic analysis has many advantages:
      automation, anti-interference, high accuracy in the resolution of overlapping
      chrom- atographic peaks. It even makes the final goal of analytical chemistry
      achievable without the aid of complicated separation procedures. The core of this
      method is the process of utilizing useful information and building models through
      chemometric algorithms. Three-way chromatographic data set can be divided into
      trilinear dataset and nontrilinear dataset, correspondingly, three-way data
      analysis (second-order tensor decomposition) algorithms can be divided into
      trilinear algorithms and nontrilinear algorithms. In this paper, three-way
      calibration used in liquid chromatography for complex chemical systems in the
      last decade is reviewed, and focused on sample pretreatment, auxiliary
      algorithms, the combination and comparison of correction algorithms.

PMID- 25764650
TI  - [Structure identification of reactive dyes by high performance liquid
      chromatography-photodiode array detection/mass spectrometry].
AB  - Based on years of experience on analyzing reactive dyes by high performance
      liquid chromatography-photodiode array detection/mass spectrometry (HPLC-DAD/MS),
      the essential applications for current structure identification of the commercial
      reactive dyes are summa- rized in three aspects. Commercial dyes always include
      several kinds of components. They are assistants for increasing solubility of
      synthetic dyes, multi-color synthetic dyes and their by-products derived from
      synthesis and storage. HPLC-DAD/MS technique can separate most of the components,
      and provide UV-Vis spectra and mass spectra individually. The separation and
      analysis can be achieved only through one injection without pre-purification of
      commercial dyes. Compared with traditional analytical methods, HPLC-DAD/MS
      technique reduces greatly not only the workload of analysis but also provides
      fully the actual compositions of the dyestuff. The reactive groups can react with
      ethanolamine or diethanolamine under moderate condition without structure
      destruction of dyes. The molecular masses before and after derivatization can be
      determined by MS, and then the type and number of reactive groups can be
      ascertained by so called "mass difference by derivative method". The chromophore
      of the dye can be identified by full spectrum scanning function of DAD. HPLC
      DAD/MS analytical technique is very special and useful for the structure analysis
      of multi-component mixed commercial dyes. As examples, the identifications of
      three multi-component mixed structures of commercial dyes (Reactive Gray,
      Reactive Supra Black and Reactive Marine Blue) were given.

PMID- 25764651
TI  - [Analysis of rice leaves proteomes by liquid chromatography-tandem, mass
      spectrometry based on the purification using a novel affinity detergent removal
      spin column].
AB  - A purification method was established for the analysis of proteomes in rice
      leaves based on a novel detergent removal spin column (DRSC). The proteins were
      extracted by phenol protein extraction method followed by sodium dodecyl sulfate
      (SDS) lysis. The lysate was purified by the detergent removal spin column and the
      enzymolytic peptides were detected by the nanoflow liquid chromatography-hybrid
      linear trap quadrupole orbitrap mass spectrometry (nanoLC-LTQ/Orbitrap). In terms
      of SDS removal efficiencies and protein identification, the method of DRSC was
      compared with those of filter aided sample preparation (FASP) and acetone
      precipitation. As a result, there were good efficiencies ( > 95%) of SDS removal
      for the three methods. With the DRSC purification strategy, 563 proteins were
      identified from rice leaves, while only 196 and 306 proteins were identified by
      FASP and acetone precipitation procedures respectively, in spite of certain
      complementarities among these identified proteins by the three methods. DRSC is
      suitable for proteins with various relative molecular masses and pI values.
      However, there were similar losses of proteins with different relative molecular
      masses and pI values with the other two methods. Using the established method,
      588 proteins were identified by once injection analysis. According to the
      molecular functions, 296 proteins with at least two identified peptides can be
      classified into eight categories with binding activity, enzyme activity,
      transporter activity, inhibitor activity, structural constitute, catalytic
      activity, other and unknown functions. The method provides technical reference
      for conducting rice proteomes.

PMID- 25764652
TI  - [Application of precursor ion scanning method in rapid screening of illegally
      added phosphodiesterase-5 inhibitors and their unknown derivatives in Chinese
      traditional patent medicines and health foods].
AB  - The compounds with similar structure often have similar pharmacological
      activities. So it is a trend for illegal addition that new derivatives of
      effective drugs are synthesized to avoid the statutory test. This bring
      challenges to crack down on illegal addition behavior, however, modified
      derivatives usually have similar product ions, which allow for precursor ion
      scanning. In this work, precursor ion scanning mode of a triple quadrupole mass
      spectrometer was first applied to screen illegally added drugs in complex matrix
      such as Chinese traditional patent medicines and healthy foods. Phosphodiesterase
      5 inhibitors were used as experimental examples. Through the analysis of the
      structure and mass spectrum characteristics of the compounds, phosphodiesterase-5
      inhibitors were classified, and their common product ions were screened by full
      scan of product ions of typical compounds. Then high performance liquid
      chromatography-tandem mass spectrometry (HPLC-MS/MS) method with precursor ion
      scanning mode was established based on the optimization of MS parameters. The
      effect of mass parameters and the choice of fragment ions were also studied. The
      method was applied to determine actual samples and further refined. The results
      demonstrated that this method can meet the need of rapid screening of unknown
      derivatives of phosphodiesterase-5 inhibitors in complex matrix, and prevent
      unknown derivatives undetected. This method shows advantages in sensitivity,
      specificity and efficiency, and is worth to be further investigated.

PMID- 25764653
TI  - [Measurement of sialic acid from lipoproteins and human plasma by liquid
      chromatography-tandem mass spectrometry].
AB  - A liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was
      established to quantify sialic acid (N-acetylneuraminic acid, NANA) from
      lipoproteins and human plasma. The method was used to investigate the different
      contents of NANA from lipoproteins between diabetic with an average age of 51.6
      years and healthy participants with an average age of 50.7 years. The NANA from
      lipoprotein samples was hydrolyzed by acetic acid (pH = 2) at 80  degrees C for 2
      h and analyzed by the optimized LC-MS/MS method after high speed centrifugation
      and filtration. The limits of detection and quantification of NANA were 7.4 and
      24.5 pg, respectively. The linear range was 2.5-80 ng/mL for NANA and the
      correlation coefficient (R2) was more than 0.998. The levels of NANA in the
      plasma of type II diabetics and healthy participants were (548.3 +/- 88.9) and
      (415.3 +/- 55.5) mg/L, respectively; and the levels of NANA from very low density
      lipoproteins (VLDL), low density lipoproteins (LDL), and high density
      lipoproteins (HDL) of the type II diabetics and the healthy participants were
      (4.91 +/- 0.19), (6.95 +/- 0.28), (3.61 +/- 0.22) MUg/mg and (2.90 +/- 0.27),
      (7.03 +/- 0.04), (2.40 +/- 0.09) MUg/mg, respectively. The sialic acid levels of
      VLDL and HDL from the type II diabetics were markedly higher than those of the
      corresponding healthy participants with the similar ages (P < 0.01). The method
      can rapidly determine the sialic acid from lipoproteins, and is reproducible and
      time saving.

PMID- 25764654
TI  - [Determination of 12 bisphenol substances in functional foods by QuEChERS and
      high performance liquid chromatography-tandem mass spectrometry].
AB  - A method based on high performance liquid chromatography-tandem mass spectrom-
      etry (HPLC-MS/MS) for the simultaneous determination of 12 bisphenol substances
      in functional foods (powder, tablet, capsule) was presented. The samples were
      extracted by acetonitrile containing 1% (v/v) acetic acid followed by further
      cleaned up using matrix solid-phase disper- sion to remove matrix interferences.
      The separation of the 12 bisphenol substances was performed on a Thermo Aquasil
      C18 column (150 mm x 4.6 mm, 3.0 MUm), and determined in the positive and
      negative MRM modes by MS/MS using matrix-matched external standard method. The
      results demonstrated that the calibration curves were of good linearity with the
      correlation coefficients greater than 0.99. The limits of detection (LODs, S/N >
      3) were in the range of 0.1-0.5 MUg/kg and the limits of quantitation (LOQs, S/N
      > 10) were 0.4-1.7 MUg/kg. The recoveries of the 12 bisphenol substances spiked
      at three levels (2.0, 5.0 and 10.0 MUg/kg) in matrix ranged from 60.5% to 116.3%
      with the relative standard deviations (RSDs) of 6.8% to 11.2%. The established
      method is simple, time-saving and sensitive. It can meet the requirements for
      current regulations while achieving qualitative and quantitative determination of
      the 12 bisphenol substances in functional foods.

PMID- 25764655
TI  - [Simultaneous determination of three estrogens in feed by solid phase extraction
      ultra performance liquid chromatography-tandem mass spectrometry].
AB  - A method was developed for the simultaneous determination of three estrogens
      (17beta-estradiol, estradiol benzoate, estradiol valerate) in feed by solid phase
      extraction-ultra performance liquid chromatography-tandem mass spectrometry (SPE
      UPLC-MS/MS). After the sample was extracted by acetonitrile and cleaned-up on a
      Heaion C18 solid phase extraction (SPE) column, the three estrogens were
      separated by an ACQUITY UPLC BEH C18 column (50 mm x 2.1 mm, 1.7 MUm) with
      gradient elution using acetonitrile and 0.1% ammonia solution as mobile phases
      and finally confirmed and quantified in multiple reaction monitoring (MRM) mode.
      The internal standard calibration curves were used for the quantification. The
      results showed that all the estrogens were determined with excellent linear
      relationships from 10 MUg/L to 200 MUg/L for 17beta-estradiol and estradiol
      valerate, and from 5 MUg/L to 200 MUg/L for estradiol benzoate. The correlation
      coefficients (r) of the three estrogens were not lower than 0. 996. The limits of
      detection for 17beta-estradiol, estradiol benzoate and estradiol valerate were 7
      MUg/kg, 5 MUg/kg and 7 MUg/kg, respectively. The average recoveries were 96.5%
      102.0%. The results demonstrated that the developed method can simultaneously
      determine the three estro- gens in feed with advantages of simple pretreatment,
      rapid analysis, low limit of detection and high accuracy.

PMID- 25764656
TI  - [Preparation of microcystin-LR molecularly imprinted polymer coated stir bar and
      its adsorptive performances].
AB  - An effective method for the preparation of magnetic molecularly imprinted
      polymers (MIPs) on attapulgite (ATP) using microcystin-LR (MC-LR) as template
      molecule through reversible addition fragmentation chain transfer (RAFT) radical
      polymerization was reported. A novel MIPs stir bar sorptive extraction (SBSE)
      coating was prepared by sol-gel method. The structure and morphology of MIPs were
      characterized by infrared spectroscopy (IR) and transmission electron microscopy
      (TEM). The adsorption performance of SBSE coated with MC-LR was studied by high
      performance liquid chromatography (HPLC). The results showed that under the
      optimized experimental conditions, the present method has high selectivity to MC
      LR. A good linearity was achieved for MC-LR over the range of 0.010-5.0 mg/L and
      the limit of detection (S/N = 3) was found to be as low as 0.27 MUg/L. The
      proposed method was successfully applied to the determination of MC-LR in water
      samples. The average recoveries ranged from 83.33% to 100.07% with the relative
      standard deviations (RSDs) of 1.40%-9.17% at three spiked levels (20, 40 and 80
      MUg/L). The developed method is rapid, selective and sensitive, and adapts to the
      analysis of trace MC in water samples.

PMID- 25764657
TI  - [Application of 1-ethyl-3-methyl imidazole L-lactate as the chiral ligand for the
      enantioseparation of amino acids].
AB  - Enantioseparation of tryptophan enantiomers (Trys), tyrosine enantiomers (Tyrs)
      and phenylamine enantiomers (Phes) by chiral ligand exchange capillary
      electrophoresis (CLE- CE) using 1-ethyl-3-methyl imidazole L-lactate ([EMIM] [L
      Lac ]) as the chiral ligand was studied. The effects of background electrolytes
      and central ions, the molar ratio and concentration of the chiral ligand and
      central ion, running buffer solution pH on the enantioseparation of Trys, Phes
      and Tyrs were investigated. Good enantioseparation of three pairs of enantiomers
      were obtained with 40.0 mmol/L [EMIM] [L-Lac] and 20.0 mmol/L cupric chloride (pH
      4.5). To validate the good behavior of [EMIM] [L-Lac], L-lactate (L-Lac) was
      further used as the chiral ligand for the enantioseparation of Trys. The contrast
      experiment showed that Trys could only be partially enantioseparated by L-Lac.
      Moreover, the enantioseparation was improved by adding 1-ethyl-3-methyl imidazole
      acetate (EMIM-Ace) which markedly prolonged the migra- tion time of Trys to more
      than 30 min. In contrast, the migration time of Trys was obtained in 15 min by
      [EMIM] [L-Lac]. Finally, the enantioseparation mechanism was further discussed.
      The experimental results showed that in the EMIM-Ace assisting L-Lac system, EMIM
      Ace was only used to suppress the electroosmotic flow and was not involved in the
      chiral ligand exchange reaction, while in the [EMIM] [L-Lac] system, the chiral
      ligand taking part in the re- action was mainly unionized [EMIM] [L-Lac] rather
      than L-Lac formed by ionized L-Lac ions.

PMID- 25764658
TI  - [Rapid detection of eight fluorescent whitening agents in textile by ultra
      performance convergence chromatography].
AB  - An accurate quantitative and confirmative method has been developed for the deter
      mination of eight fluorescent whitening agents (FWAs) in textile by ultra
      performance conver- gence chromatography (UPC2) coupled with photo diode array
      (PDA) detection, including 1,2-bis (5-methyl-2-benzoxazole) ethylene (PF), 7
      diethylamino-4-methylcoumarin (SWN), 2, 2'-(2,5-thiophenediyl) bis(5-(1,1
      dimethylethyl)-benzoxazol (OB), 2-[4-[2-[4-(2-benzox- azolyl) phenyl] ethenyl]
      phenyl] -5-methyl-benzoxazol (KSN), 1,4-bis (2-cyanostyryl) benzene (ER-I), 1-(2
      cyanostyryl)-4-(4-cyanostyryl) benzene (ER-II), 2,2'-(1,4-naphthalenediyl) bis
      benzoxazol (KCB), 4,4'-bis[2-(2-methoxyphenyl) ethenyl]-1,1'-biphenyl (FP). The
      sample was extracted with xylene and concentrated by a rotary evaporator, and
      then qualitatively and quantitatively analyzed by UPC2. The separation of target
      compounds was achieved on an ACQUITY UPC2 HSS C18 SB column (100 mm x 3.0 mm, 1.8
      MUm) by a gradient elution with supercritical carbon dioxide and methanol as
      mobile phases. External standard method was used for the quantitative
      determination and the calibration curves showed good linearity in the
      concentration range of 1.0-20.0 mg/L for the eight target compounds with
      correlation coefficients not less than 0.999 1. The limits of quantification of
      the eight compounds (LOQs, S/N = 10) were 0.70-0.95 mg/L. The average recoveries
      of the eight compounds ranged from 90.9% to 96.5% at the spiked levels of 2.0,
      5.0, 10.0 mg/kg with the relative standard deviations (RSDs) of 2.8%-4.2%. The
      method is simple, accurate and time-saving with high sensitivity, and can be used
      for the rapid determination of the eight FWAs in textile.

PMID- 25764659
TI  - [[Molecular composition of saturated hydrocarbons in diesels by comprehensive two
      dimensional gas chromatography coupled with time-of-flight mass spectrometry]].
AB  - An analytical method for separation and identification of the saturated
      hydrocarbons in diesels at molecular level by comprehensive two-dimensional gas
      chromatography coupled with time-of-flight mass spectrometry (GC x GC-TOF MS)was
      established. The saturated hydrocarbons were pre-separated from diesel samples by
      solid phase extraction before GC x GC-TOF MS analysis. More than 1,000 individual
      compounds (including paraffins, naphthenes and ole- fins) in coker diesel were
      tentatively identified based on NIST library search, mass spectrum resolution,
      boiling point distribution law and separation characteristics. Normal paraffins
      showed great regularity and could be identified easily through the relative
      position with pristane and phytane. The cyclic alkanes arranged above paraffins
      with the increasing number of rings. The normal alkyl cyclohexanes and
      cyclopentanes were well distinguished due to the difference of their polarity.
      Normal alpha-olefins which were often neglected in the past were also identified.
      With the support of the above-introduced identification, the distribution by
      structural type and carbon number were presented using peak area normalization.
      This analytical method was suc- cessfully used to investigate the molecular
      composition of saturated fractions in different diesel samples. All the results
      indicated that the molecular compositions of saturates in catalytic cracking
      diesel and coker diesel were significantly different because of the processing
      mechanism. This method provided technical support for the characterization of
      saturated hydrocar- bons in diesels and the investigation of processing
      mechanism.

PMID- 25764660
TI  - [Sample pretreatment for the measurement of phthalate esters in complex
      matrices].
AB  - Sample pretreatment methods for the measurement of phthalate esters (PAEs) by gas
      chromatography-mass spectrometry (GC-MS) in various complex matrices, including
      sediment, soil, suspended particle matter, urban surface dust, Sinonovacula
      Constricta, cosmet- ic, leather, plastic and coastal/estuarine seawater, were
      proposed. The pretreatment which was appropriate for GC-MS detection was focused
      on the investigation and optimization of oper- ating parameters for the
      extraction and purification, such as the extraction solvent, the eluant and the
      adsorbent of solid phase extraction. The results of the study of pretreatment for
      various complex matrices showed that methylene chloride was the best solvent for
      the ultrasonic extraction when solid-liquid extraction was used; silica gel was
      the economical and practical adsorbent for solid-phase extraction for
      purification; C18 was the most commonly adsorbent for preconcentration of PAE in
      coastal/estuarine seawater sample; the mixed solution of n-hexane and ethyl
      acetate with a certain proportion was the suitable SPE eluent. Under the
      optimized conditions, the spiked recoveries were above 58% and the relative
      standard deviations (RSDs) were less than 10.5% (n = 6). The detection limits
      (DL, 3sigma) were in the range of 0.3 MUg/kg (dibutyl phthalate)--5.2 MUg/kg (
      diisononyl phthalate) for sediment, and 6 ng/L (dipropyl phthalate)--67 ng/L
      (diisodecyl phthalate) for costal/estuarine seawater. The pretreatment meth- od
      for various complex matrices is prominent for the measurement of the 16 PAEs with
      GC-MS.

PMID- 25764661
TI  - [Generic method for determination of volatile organic solvents in cosmetics].
AB  - A generic screening, confirmation and determination method was established based
      on 36 commonly used volatile organic solvents in cosmetics by headspace gas
      chromatography- mass spectrometry (GC-MS). This method included a database for
      pilot screening and identifi- cation of those solvents and their quantitative
      method. Pilot screening database was composed by two sections, one was household
      section built by two columns with opposite polarities (col- umn VF-1301 ms and DB
      5 ms) using retention index in different column systems as qualitative parameter,
      and the other was NIST MS search version 2.0. Meanwhile, the determination method
      of the 36 volatile solvents was developed with GC-MS. Cosmetic samples were
      dissolved in water and transferred to a headspace vial. After 30 min
      equilibration at 60  degrees C, the samples were analyzed by GC-MS equipped with
      a capillary chromatographic column VF-1301 ms. The external calibration was used
      for quantification. The limits of detection were from 0.01 to 3.3 MUg/g, and the
      recoveries were from 60.77% to 126.6%. This study provided a generic method for
      pilot screening, identification, and quantitation of volatile organic solvents in
      cosmetics, and may solve the problem that different analytical methods need to be
      developed for different targeted compounds and pilot screening for potential
      candidate solvent residues.

PMID- 25764662
TI  - [Determination of 19 phthalate esters in cucumbers using QuEChERS coupled with
      gas chromatography-triple quadrupole mass spectrometry].
AB  - An efficient method using QuEChERS equipped with triple quadrupole GC-MS/MS for
      the simultaneous detection of 19 phthalate acid ester residues in cucumbers was
      established. The phthalate acid esters were extracted from cucumber samples by
      ultrasonic with acetonitrile. The extracts were salted out and centrifuged with
      anhydrous magnesium sulfate and sodium chloride. The supernatants were enriched
      by vacuum distillation, and then purified by C18 adsorbent. The 19 phthalate
      esters were separated on an HP-5ms UI column (30 mx 0.25 mm x 0.25 MUm), and
      determined using MS/MS in multiple reactions monitoring mode. The method showed
      favorable qualitative and quantitative analysis of the phthalate esters with good
      linearity (r >= 0.9995) in the linear range of 10-5,000 MUg/kg and the limits of
      detection (LODs) were 0.2-3.5 MUg/kg. With the proposed method, the recoveries
      were evaluated in cucumbers at the spiked levels of 10, 100 and 500 MUg/kg. The
      results showed that the average recoveries were ranged from 63.3%-127.8% and the
      relative standard deviations (RSDs) were 0.5%-13.3%. In short, the proposed
      method with high sensitivity and good accuracy can meet the determination
      requirements for multi-residues. Furthermore, the method can be applied for the
      simultaneous determination of phthalate acid esters in cucumbers.

PMID- 25764663
TI  - [Determination of indicator polychlorinated biphenyls in vegetable oils by double
      clean-up-gas chromatography].
AB  - To investigate the residues of seven indicator polychlorinated biphenyls (PCBs)
      in vegetable oils, a method was established for the determination of trace PCBs
      in vegetable oils by double clean-up coupled with gas chromatography (GC). After
      extracted with acetonitrile, the sample extract was concentrated to dryness
      followed by re-dissolving with hexane. And the solution was pretreated by adding
      concentrated sulfuric acid followed cleaned-up with silica gel in dispersive
      solid-phase extraction protocol, then analyzed by GC with external standard meth-
      od. Under the optimized chromatographic conditions, the analysis was carried out
      with a capillary column (HP-5, 30 m x 0.32 mm x 0.25 MUm) at a flow rate of 0.8
      mL/min, and the sample volume was 1.00 MUL. Monitoring with an electron-capture
      detector, all the target analytes were separated by temperature-programming of
      the column. Good linearities were obtained in the range of 10-500 MUg/L for the
      seven indicator PCBs with the correlation coefficients greater than 0. 999. For
      different matrices, the limits of detection (S/N = 3) and limits of quantitation
      (S/N = 10) were in the range of 1.8-8.9 pg/kg and 5.9-29.8 MUg/kg, respectively.
      At three spiked levels of 10, 20 and 100 MUg/kg of the seven indicator PCBs in
      olive oil, palm oil and peanut oil blank samples, the average recoveries ranged
      from 71.0% to 105.5% with the RSDs of 4.0%-11.3%. The method is simple, rapid and
      accurate, and can be used for the routine analysis of the indicator PCBs in
      vegetable oils.

PMID- 25764664
TI  - [Protein enrichment based on large volume recycling injection].
AB  - Biological proteins have great differences in size, hydrophobicity, pH and
      relative abundance. Especially, the relative contents of high-abundance proteins
      and low abundance proteins can reach 11 orders of magnitude or more in blood.
      However, the contents of proteins which have an important impact on the
      biological function and have related to major diseases are usually very low in
      body fluids or tissues. So, it is very meaningful to detect the low abundance
      proteins in biological samples. A method of large volume recycling injection was
      developed as a new sample enrichment technology in this study. The low absolute
      contents of pro- teins in a sample were improved by increasing the volume of
      sample, and the enrichment efficiency was also increased with the addition of
      injection times. With the pork liver protein as an example, under the optimized
      conditions, the representative contents which were no peaks or little peaks and
      more peaks with low signals were studied. The contents of peaks at the retention
      times of 11.38 min and 12.58 min were enriched by 11 time injections of 500 MUL
      each time. The enrichment factors respectively reached 52 and 61 which were
      closed to theoretical values. This method can be used for the enrichment of
      biological protein samples.

PMID- 25764665
TI  - [Determination of principal components and related substances in adenosine
      disodium triphosphate preparation by ion chromatography].
AB  - A new method was developed for the determination of adenosine disodium triphos-
      phate (ATP-Na2 ) and its related substances in ATP-Na2 preparation by ion
      chromatography (IC). The sample was diluted with ultrapure water and filtrated by
      0.22 MUm polyether sulfone filter membrance, and then analyzed by IC directly
      without any more pretreatment. The analysis was performed on a Dionex IonPac AS11
      HC column (250 mm x 4 mm) and a guard column Ion-Pac AG11-HC (50 mm x 4 mm). A
      KOH eluent generator cartridge was used for gradient elution at the flow rate of
      1.0 mL/min. The detection was performed by a Dionex suppressed (Dionex AERS 500 4
      mm) conductivity detector. The injection volume was 10 MUL. The assay was
      quantitatively completed by external standard method and the related substances
      were calculated with correction factors. The linear ranges of the method for ATP
      Na2, adenosine disodium diphosphate (ADP-Na2) and adenosine disodium
      monophosphate (AMP-Na2) were 0.000 146-1.83 g/L (r = 0.9997), 0.000484-1.51 g/L
      (r = 0.9996) and 0.000426-0.804 g/L (r = 0.9999), respectively. The average
      recoveries of ATP-Na2 were 96.50%, 96.57% and 96.77% at three spiked levels. The
      limits of quantitation (S/N = 10) of ATP-Na2, ADP-Na2 and AMP-Na2 were 1.5 ng,
      4.8 ng, 4.3 ng, and the limits of detection (S/N = 3) were 0.58 ng, 1.21 ng, 1.28
      ng, respectively. The results demonstrated that the system has the advantages of
      high sensitivity, facile automation and simple sample pretreatment. The method is
      suitable for the quality control of adenosine disodium triphosphate preparations.

PMID- 25764666
TI  - [Determination of oxygenates in syngas-to-olefin products by solid phase
      extraction combined with gas chromatography-mass spectrometry].
AB  - The syngas-to-olefin (SGTO) products mainly consist of hydrocarbons along with
      small amounts of oxygenates as the byproducts. A C18 solid-phase extraction (SPE)
      column was used for oxygenates enrichment in SGTO products. As the hydrophobic
      compounds, the hydrocarbons had stronger interaction with a C18 SPE column than
      oxygenates. Under the optimized elution conditions, the oxygenates were first
      eluted from the C18 SPE column with 60% (v/v) methanol solution. The fraction of
      oxygenates was then analyzed with gas chromatography-mass spectrometry (GC-MS)
      for qualification and gas chromatography-hydrogen flame ionization detection (GC
      FID) for quantification. The FID response factors of n-alkanol and n-ketone were
      used for alkanols and ketones quantitative calculation and the method recoveries
      were 88%-98% and 64%-87% respectively. In the range of 197-4,785 mg/L, good
      linear relationships of the FID responses with the corresponding mass
      concentrations of the standard samples were obtained with the linear regression
      coefficients greater than 0.99. Sixty-seven oxygenates were analyzed
      qualitatively and quantitatively. The results showed that the fraction of the
      oxygenates mainly consists of alkanols and ketones. The total content of the
      oxygenates in SGTO products was 6.2%. The enrichment method only requires a very
      small amount of sample and the total process can be completed within 10 min. The
      analysis results of SGTO product studies can provide the necessary basic data for
      SGTO catalysts and dynamics studies.

PMID- 25764668
TI  - [Lifecycle of HCV and point of action of the anti-HCV drugs].

PMID- 25764667
TI  - [Determination of 16 phthalate acid ester residues in health wine by gas
      chromatography-triple quadrupole mass spectrometry].
AB  - A method for the analysis of sixteen phthalate acid ester (PAE) residues in
      health wine was developed using gas chromatography-triple quadrupole mass
      spectrometry (GC-QQQ- MS). The health wine samples were extracted with n-hexane
      by liquid-liquid extraction method before analysis. The samples were detected by
      GC-QQQ-MS with electron impact source (EI) in selected ion monitoring (SIM) mode
      after extraction. The separation was performed on an HP-5MS capillary column (30
      m x 0.25 mm x 0.25 MUm) with temperature programming. The retention time and the
      fragment ion abundance ratio were used to judge the qualitative results, and the
      quantitation was performed with standard curve method of the characteristic ion
      chrom- atographic peak area-concentration. Eighty-one batches of health wine
      samples were detected using the method. The results showed that the method had
      good linear relationships with correlation coefficients (r2) not less than 0.995
      9. The recoveries of fifteen PAEs ranged from 88.6% to 107. 3% except dimethyl
      phthalate (DMP) which was 52.3%-58.7% in all the three spiked levels with the
      relative standard deviations of 0.1%-6.8% (RSD, n = 6). The limits of detection
      were between 0.002 mg/L to 0.061 mg/L. The limits of quantification were between
      0.005 mg/L and 0.202 mg/L. The method is accurate, sensitive, proprietary and
      suitable for the simultaneous determination of the sixteen phthalate acid esters
      in health wine.

PMID- 25764669
TI  - [Development of antiviral treatments for chronic hepatitis C].
AB  - The antiviral therapy for chronic hepatitis C has been developed since HCV was
      discovered in 1989. As for the patients with genotype 1, sustained virological
      response rate by interferon monotherapy was less than 20% in 1990's; the rate has
      been improved today to 85% by direct-acting antivirals. The prevention of
      development of liver cirrhosis and hepatocellular carcinoma will be expected.

PMID- 25764670
TI  - [Natural history of hepatitis C virus infection].
AB  - Over 70% of individuals acutely infected with hepatitis C virus (HCV) develop
      chronic infection at significant risk of progressive liver fibrosis and
      subsequent liver cirrhosis and hepatocellular carcinoma. Various viral, host, and
      environmental factors have been reported to affect the natural history of HCV
      infection such as chronicity in acute phase and disease progression in chronic
      phase. Recent genome-wide association studies (GWAS) identified several host
      factors which are associated with treatment efficacy and clinical course in HCV
      infection. In this review, we focus on the host factors identified by GWAS,
      especially on HCV spontaneous clearance and disease progression in chronic HCV
      infection.

PMID- 25764671
TI  - [Epidemiology of hepatitis C virus infection in Japan].
AB  - In Japan, a new era of treatment of HCV infection has come. The issues of
      hepatitis measures at present are that the HCV carrier in need of treatment is
      linked to the received treatment properly in conjunction with the improvement of
      hepatitis screening consultation rate and the promotion of treatment introduction
      rate with medical institutions consultation rate after hepatitis screening.

PMID- 25764672
TI  - [Host factors and viral factors in hepatitis C treatment].
AB  - In the interferon-based therapy for hepatitis C, host factors such as age,
      gender, liver fibrosis and steatosis are important as a therapeutic effect
      predictor, and viral factors such as HCV genotype, HCV viral load, HCV gene
      (IL28B, ITPA) are also important. In addition in genotype 1b, ISDR/IRRDR and core
      amino acid substitution are important. Also in the DAA treatment, viral factors
      are also important at the view of therapeutic effect and difficulty of
      acquisition of drug resistance mutation. In addition, the goal of treatment of
      hepatitis C are suppression of liver fibrosis progression and liver cancer and
      improvement of quality of life due to this (quality of life: QOL) and life
      prognosis, it is important to understand the host factors and HCV viral factors.

PMID- 25764673
TI  - [Guidelines for the treatment of chronic hepatitis and cirrhosis due to hepatitis
      C virus infection for the fiscal year 2014 in Japan].
AB  - In the 2014 guidelines for the treatment of patients with chronic hepatitis C,
      Simeprevir, pegylated interferon (Peg-IFN) and ribavirin combination therapy for
      24 weeks are indicated to treatment-naive patients infected with hepatitis C
      virus (HCV) of genotype 1. Retreatment is aimed to either eradicate HCV or
      normalize transaminase levels for preventing the development of hepatocellular
      carcinoma(HCC), taking into consideration causes for the failure in the initial
      treatment. Moreover, daclatasvir plus asunaprevir are indicated to interferon
      ineligible/intolerant patients and nonresponder(null and partial) patients
      infected genotype 1b. For patients with compensated cirrhosis, the clearance of
      HCV RNA is aimed toward improving histological damages and decreasing the
      development of HCC. When the prevention of HCC is at issue, not only IFN, but
      also liver supportive therapy such as Stronger Neo-Minophagen C, ursodeoxycholic
      acid, phlebotomy, branched chain amino acids (BCAA), either alone or in
      combination, are given.

PMID- 25764674
TI  - [JSH guidelines for the management of hepatitis C virus infection (version 3)].
AB  - Recently, the management of chronic hepatitis C virus (HCV) has been greatly
      advanced with introduction of direct acting antivirals (DAAs) in clinical
      setting. The Japan Society of Hepatology (JSH) first released the clinical
      practice guideline for the management of HCV infection in 2012, and revised in
      2013 along with the introduction of a second-generation DAA, simeprevir (SMV). In
      September 2014, the first IFN-free DAAs, daclatasvir (DCV) and asunaprevir (ASV),
      were launched and the antiviral therapy for IFN intolerant/ineligible patients
      became to be possible. Thence the society has now revised the clinical practice
      guidelines at this time, and added a new treatment flow-chart for the antiviral
      therapy in patients with cirrhosis. In this article I summarized the revised
      guidelines and would like to introduce the treatment recommendations.

PMID- 25764675
TI  - [Recognition mechanism of hepatitis C viral infection].
AB  - In the viral reproduction, hepatitis C virus(HCV) produces double-stranded RNA
      (dsRNA) as a replication intermediate. RIG-I(retinoic acid inducible protein I)
      recognizes the intracellular HCV dsRNA as a "non self" molecule, and triggers the
      induction of interferon (IFN)-beta and then numerous IFN-stimulated genes(ISGs).
      On the other hand, one of toll-like receptors, TLR3 also recognizes the
      extracellular HCV dsRNA, and subsequently triggers the induction of IFN-beta and
      ISGs. We recently reported class A scavenger receptor (MSR1) was required for
      TLR3-mediated recognition of the extracellular HCV dsRNA. In this review, we
      summarize current knowledge about RIG-I- and TLR3/MSR1-mediated recognition
      mechanisms of HCV infection.

PMID- 25764676
TI  - [Chronic hepatitis C virus infection attenuates host antiviral innate immune
      response].
AB  - The innate immune system is essential for controlling viral infection. Hepatitis
      C virus (HCV) is a causative agent of hepatocellular carcinoma. HCV evades host
      innate immune response and maintains persistent infection. RIG-I is a cytoplasmic
      viral RNA sensor and triggers the innate immune response. The Riplet ubiquitin
      ligase mediates K63-linked polyubiquitination of RIG-I, which is essential for
      RIG-I activation. Previous studies have shown that HCV NS3-4A protease cleaves
      RIG-I adaptor MAVS to escape host antiviral response. However, MAVS cleavage is
      supposed to be not sufficient for viral chronicity. Recently, we found that NS3
      4A cleaves both MAVS and Riplet to attenuate RIG-I activation. These findings
      indicate that HCV NS3-4A cleaves several proteins to shut off antiviral innate
      immune response.

PMID- 25764677
TI  - [Development of the novel oral vaccine against hepatitis C virus utilizing
      bifidobacteria].
AB  - Approximately 3% of the world people have chronically infected with hepatitis C
      virus (HCV), and about 30% of those will develop progressive liver disease, such
      as cirrhosis and hepatocellular carcinoma. The current standard treatment for HCV
      of a combination of pegylated interferon-alpha with ribavirin and the development
      of new direct-acting antiviral agents, have dramatically improved the virus
      eradication rate. However those treatments have some toxicities and too expensive
      to be applied in developing countries, where have high HCV infection rates.
      Therefore there is a still great need to develop the novel vaccines, which can
      protect or treat HCV infection with the high efficacies and low adverse effects
      and costs. Currently we are developing the novel oral vaccine against HCV
      utilizing bifidobacteria.

PMID- 25764678
TI  - [Outline of HCV treatment].
AB  - All-oral combinations of direct-acting antivirals improve efficacy and safety
      outcomes for patients with hepatitis C virus infection, particularly those who
      are poor candidates for current interferon/ribavirin-based regimens. The
      frequency of adverse events was also low, especially compared with historical
      data in patients receiving a triple regimen with NS3/4A protease inhibitor and
      peginterferon/ribavirin. However, there was apparent association between
      preexisting NS5A resistance-associated variants and virologic failure.
      Furthermore, both NS5A and NS3 resistance-associated variants were also detected
      in most patients with virologic failure. In conclusion, more effective
      therapeutic regimens should be selected, based on further understanding of
      efficacy and safety in each of drugs.

PMID- 25764679
TI  - [Pegylated interferon plus ribavirin combination therapy for patients with
      chronic hepatitis C].
AB  - The antiviral therapy for patients with chronic hepatitis C virus(HCV) infection
      has changed from interferon(IFN) monotherapy to dual therapy with IFN plus
      ribavirin(RBV), moreover pegylated IFN(Peg-IFN) plus RBV. The sustained virologic
      response(SVR), defined as HCV RNA negativiation at 24 weeks after the treatment,
      were obtained 50% among the patients with genotype 1 (48 weeks treatment) and 80%
      among those with genotype 2 (24 weeks treatment) in Peg-IFN plus RBV combination
      therapy. The baseline host factors such as age, the degree of liver fibrosis
      progression and a genetic polymorphism near the IL28B gene, the viral factors
      such as HCV genotype, mutant virus at HCV core region and interferon sensitivity
      determining region, the treatment factors such as drug adherence and treatment
      duration have been reported to be associated with SVR. The risk for
      hepatocellular carcinoma (HCC) incidence was significantly lower in SVR patients
      than non-SVR patients. Especially, alpha-fetoprotein (AFP) levels decreased
      through therapy, and the patients with < 5 ng/mL had a low potential of HCC
      incidence regardless of HCV eradication. It is suggested that AFP levels at 24
      weeks after the treatment can be a good surrogate marker for HCC incidence
      irrespective of the virologic response.

PMID- 25764680
TI  - [Combined telaprevir plus ribavirin and pegylated interferon therapy for patients
      with chronic hepatitis C].
AB  - Antiviral efficacy of combined Peg-IFN-alpha2b plus ribavirin therapy was
      improved by the addition of telaprevir, a first-generation NS3/4A protease
      inhibitor, in patients with chronic hepatitis due to HCV infection. A multicenter
      prospective study revealed that the triple therapy with telaprevir administered
      according to an algorithm based on the drug adherence, IL28B polymorphism and
      viral response yielded a high SVR rate through attenuation of viral relapse by
      prolonged ribavirin/Peg-IFN-alpha2b administration. Such triple therapy, however,
      may provoke various adverse effects potentially necessitating treatment
      discontinuation; dermatitis, hemolytic anemia, hyperuricemia, renal impairment
      and retinopathy. Thus, the role of telaprevir as a direct-acting antiviral agent
      used in combination with Peg-IFN and ribavirin for patients with genotype 1b HCV
      infection was replaced by simeprevir, a second-generation NS3/4A protease
      inhibitor. However, telaprevir still plays an important role in the treatment for
      patients with genotypes 2a and 2b HCV infection as well as those showing viral
      breakthrough after antiviral therapies using second-generation NS3/4A protease
      inhibitors.

PMID- 25764681
TI  - [A triple combination therapy of simeprevir, pegylated-interferon and ribavirin
      with chronic hepatitis C virus genotype 1 infection].
AB  - A triple combination therapy of simeprevir (SMV), pegylated-interferon and
      ribavirin (PR) was released to clinical practice in Japan on December of 2013,
      ahead of the rest of the world. This regimen is recommended for genotype 1
      hepatitis C in AASLD, EASL and WHO guidelines based the data of phase III trials.
      CONCERTO-1, 2, 3, 4 were phase III trial in Japan investigated efficacy and
      safety of simeprevir once daily with peginterferon alpha2a or alpha2b/ribavirin
      combination therapy in treatment-naive and treatment-experienced patients with
      genotype 1 HCV infection. SMIV/PR combination therapy provided high sustained
      virologic response rate 12 weeks after treatment end in both treatment-naive and
      treatment-experienced patients with a 24-week treatment duration.

PMID- 25764682
TI  - [Natural human IFNbeta and ribavirin combination therapy].
AB  - Chronic hepatitis C virus (HCV) infection results in scarring of the liver and
      ultimately cirrhosis, liver failure, and hepatocellular carcinoma. One goal of
      hepatitis C treatment is eradication of the virus, which typically leads an
      improvement in liver fibrosis. Combination therapies that include interferons
      (IFNs) and ribavirin increase the rate of a sustained virological response (SVR).
      Moreover, triple therapy containing direct acting antiviral agents (DAAs)
      dramatically improves SVR rate, particularly in patients infected with high titer
      genotype 1b HCV. However, these treatments are accompanied by many serious
      adverse effects, such as cytopenia and depression, specifically in the elderly.
      Natural human IFNbeta and ribavirin combination therapy is currently available in
      Japan and is associated with a lower incidence of side effects as compared with
      IFNalpha (Peg-IFNalpha) and ribavirin. Therefore, clinicians should bear IFNbeta
      and ribavirin combination therapy in mind as a well-tolerated and effective
      option for chronic hepatitis C treatment.

PMID- 25764683
TI  - [PEG-IFN/IFN monotherapy].
AB  - Pegylated-interferon(PEG-IFN)/interferon monotherapy for patients with chronic
      hepatitis C has been used for two clinical aims; one is for the elimination of
      hepatitis C virus (HCV), and the other is for the inhibition of
      hepatocarcinogenesis. In patients with a rapid viral response to PEG-IFN, PEG-IFN
      monotherapy can efficiently eradicate HCV with decreased side effects. A low dose
      treatment of interferon is suggested to inhibit hepatocarcinogenesis in patients
      whose ALT or alpha-fetoprotein (AFP) was reduced in response to the treatment,
      although the benefits and adverse events of IFN therapy have to be carefully
      evaluated.

PMID- 25764684
TI  - [Interferon-free treatment for patients with chronic hepatitis C].
AB  - Oral combinations of direct acting antivirals (interferon-free) improve efficacy
      and safety outcomes for patients with hepatitis C virus (HCV) infection. In
      Japanese phase 3 study of daclatasvir plus asunaprevir combination therapy for 24
      weeks, 222 patients with chronic HCV genotype 1b infection were enrolled. SVR was
      achieved by 87% of interferon-ineligible/intolerant patients and 81% of
      nonresponder patients; rates were similar in cirrhosis (91%) and noncirrhosis
      (84%) patients, and in patients with IL28B CC (85%) or non-CC (85%) genotypes.
      The rate of serious adverse events was low among patients. Other oral combination
      therapies (interferon-free) are ongoing in Japan. Interferon-free all-oral
      therapy is well tolerated and can achieve a high rate of SVR in patients with HCV
      genotype 1b.

PMID- 25764685
TI  - [Anti-HCV treatment for older patients].
AB  - The prevalence of older patients has been increasing in Japan, and this is an
      impending problem in other countries where viral spread has occurred more
      recently. The risk for hepatocellular carcinoma (HCC) depended on age, and
      increased after 65 years of age. Even when stratified by stage of fibrosis, the
      cumulative and annual incidences of HCC were significantly higher in older
      patients than in younger patients (p < 0.001) at the same stage of fibrosis. The
      impact of hepatitis C viral (HCV) eradication on HCC prevention was less
      significant in older patients than in younger patients. Patients should therefore
      be identified at an earlier age and treatment should be initiated. Treatment
      strategy for older patients with HCV should be decided in consideration with
      interferon eligibility, response to interferon therapy, presence of resistant
      associated variant in the NS5A, and risk of HCC.

PMID- 25764686
TI  - [Treatment for chronic hepatitis C with thrombocytopenia].
AB  - Thrombocytopenia in patients with chronic hepatitis C represents an obstacle for
      the initiation of antiviral treatment. Antiviral treatment with pegylated
      interferon alpha and ribavirin has contributed to a significant increase in the
      rate of sustained virological response. However, patients with thrombocytopenia
      is ineligible for antiviral treatment or, if able to start treatment, may require
      a dose reduction or even discontinuation due to the haematological adverse
      effects. We here review the efficacy and safety of antiviral treatment after
      splenectomy and partial splenic embolization, and the potential effect of
      platelet count increase by interferon beta.

PMID- 25764687
TI  - [Hepatitis C virus infection and hemodialysis: update 2014].
AB  - Since hepatitis C virus (HCV) infection is much common among hemodialysis (HD)
      patients, the natural history of HCV is not sufficiently understood. It has been
      reported that HCV infection is one of the major risk factors for the lower
      survival among HD patients. Recent progression of the therapy involving direct
      acting antiviral (DAA) can eliminate HCV infection in almost HCV infected
      patients, resulting HD patients should also get this benefit. Though HD patients
      have many restricted factors for accepting anti HCV therapy, the significance of
      clinical usefulness of interferon beta that has less adverse effect should be
      more deeply considered with newly developed DAAs for eliminating HCV infected HD
      patients.

PMID- 25764688
TI  - [Treatment strategy for the recurrence of HCV infection after liver
      transplantation in the era of DAA].
AB  - Chronic hepatitis C virus (HCV) infection is a leading cause of end stage liver
      disease and one of the leading indications for liver transplantation (LT).
      Recurrence of HCV infection following LT is almost universal and can accelerate
      graft cirrhosis. However, interferon alfa-based regimens used to treat recurrent
      HCV infection after LT are poorly tolerated, associated with generally modest
      efficacy, and can interact with immunosuppressive agents. To improve the efficacy
      of pre- and post-transplant antiviral therapy, a new class of potent direct
      acting antiviral agents (DAAs) has been developed. The aim of this review is to
      summarize the use of DAAs in LT HCV patients.

PMID- 25764689
TI  - [New era of the treatment against hepatitis C virus].
AB  - Interferon (IFN) and ribavirin (RBV) have remained as key drugs in the treatment
      against hepatitis C virus (HCV) for a past decade. Although the IFN and RBV based
      therapy has been greatly improved, indication of the IFN based therapy is limited
      because of its side effects. Thus, new types of drugs against HCV have been
      awaited. Now many direct acting antivirals (DAAs) targeting protease, NS5A and
      polymerase of HCV have been developed and many clinical trials with new DAAs are
      ongoing. Furthermore, some of the trials have already shown outstanding results
      with high curative rate reaching almost 100% and very low rate of adverse events.
      The IFN free regimens with new DAAs would completely change the treatment against
      HCV.

PMID- 25764690
TI  - [Direct-acting antiviral-resistant variant].
AB  - Recently, IFN-free NS5A inhibitor daclatasvir and protease inhibitor asunaprevir
      combination treatment was approved for genotype 1b HCV-infected patients who were
      ineligible or who failed to respond to previous therapies. NS5A inhibitor
      resistant variants occasionally exist in HCV-infected patients who have never
      been exposed to direct-acting antivirals. In Japanese HCV genotype 1b-infected
      patients, the frequency of NS5A inhibitor-resistant variants is approximately 11
      23 %. The phase 3 study of daclatasvir and asunaprevir combination therapy showed
      that more patients with NS5A 31 and/or 93 resistance-associated variants
      experienced virological failure. Preexisting NS5A inhibitor-resistant variants
      should be evaluated carefully before choosing the drugs.

PMID- 25764691
TI  - [Factual investigation for the patients with viral hepatitis].
AB  - We performed patients survey for the liver disease patients including hepatitis
      B, hepatitis C and hepatocellular carcinoma. The results obtained from this
      patients survey indicated that the liver disease patients had a diversity of
      social, economical and mental troubles. The medical staffs should support liver
      disease patients based on the understanding for the difference of background of
      the patients.

PMID- 25764692
TI  - [Hepatitis C virus induced hepatocellular carcinoma associated genes].
AB  - Hepatitis C virus (HCV) infection is a major risk factor for developing
      hepatocellular carcinoma (HCC). The host genetic factors involved in the
      development of HCC in patients with HCV infection were investigated. To identify
      the genetic susceptibility factors for HCV-induced HCC, genome wide association
      studies (GWAS) were conducted in HCV-induced HCC cases and controls of Japanese
      origin. Single nucleotide polymorphisms (SNPs) which showed possible association
      in the GWAS were further genotyped using different cohorts. By these analyses,
      MICA and DEPDC5 SNPs were found to be strongly associated with HCV-induced HCC.
      These results highlight the importance of MICA and DEPDC5 genetic variations not
      only as predictive biomarkers for HCV-induced HCC but also as therapeutic targets
      against hepatocarcinogenesis or HCC.

PMID- 25764693
TI  - [Wolfram syndrome: clinical features, molecular genetics of WFS1 gene].
AB  - Wolfram syndrome(WFS: OMIM 222300) is a rare recessive neuro-endocrine
      degenerative disorder, known as DIDMOAD(Diabetes Insipidus, early-onset Diabetes
      Mellitus, Optic Atrophy and Deafness) syndrome. Most affected individuals carry
      recessive mutations in the Wolfram syndrome 1 gene(WFS1). The WFS1 protein is an
      endoplasmic reticulum(ER) embedded protein, which functions in ER calcium
      homeostasis and unfolded protein responses. Dysregulation of these cellular
      processes results in the development of ER stress, leading to apoptosis. In
      addition, abundantly present WFS1 protein in insulin secretory granules plays a
      role in the intra-granular acidification. However, the phenotypic pleiomorphism
      and molecular complexity of this disease limit the understanding of WFS. Here we
      review clinical features, molecular mechanisms and mutations of WFS1 gene that
      relate to this syndrome.

PMID- 25764694
TI  - My view: mental illness is a medical issue.

PMID- 25764695
TI  - My view: mental illness is a human issue.

PMID- 25764696
TI  - How to become a national brand.

PMID- 25764697
TI  - Top policy issues for 2015.

PMID- 25764698
TI  - Medication cost-cutting plans burden patients and clinicians.

PMID- 25764699
TI  - ASAM criteria becomes electronic tool.

PMID- 25764700
TI  - Behavioral healthcare EHR survey.

PMID- 25764701
TI  - More ACOs look toward behavioral healthcare integration.

PMID- 25764702
TI  - Minnesota mental health center for children LETs in natural light.

PMID- 25764703
TI  - [Feature extraction of motor imagery electroencephalography based on time
      frequency-space domains].
AB  - The purpose of using brain-computer interface (BCI) is to build a bridge between
      brain and computer for the disable persons, in order to help them to communicate
      with the outside world. Electroencephalography (EEG) has low signal to noise
      ratio (SNR), and there exist some problems in the traditional methods for the
      feature extraction of EEG, such as low classification accuracy, lack of spatial
      information and huge amounts of features. To solve these problems, we proposed a
      new method based on time domain, frequency domain and space domain. In this
      study, independent component analysis (ICA) and wavelet transform were used to
      extract the temporal, spectral and spatial features from the original EEG
      signals, and then the extracted features were classified with the method combined
      support vector machine (SVM) with genetic algorithm (GA). The proposed method
      displayed a better classification performance, and made the mean accuracy of the
      Graz datasets in the BCI Competitions of 2003 reach 96%. The classification
      results showed that the proposed method with the three domains could effectively
      overcome the drawbacks of the traditional methods based solely on time-frequency
      domain when the EEG signals were used to describe the characteristics of the
      brain electrical signals.

PMID- 25764704
TI  - [EEG-EMG coherence analysis of different hand motions in healthy subjects].
AB  - It is the functional connectivity between motor cortex and muscle that directly
      relates to the rehabilitation of the dysfunction in upper limbs and neuromuscular
      activity status, which can be detected by electroencephalogram-electromyography
      (EEG-EMG) coherence analysis. In this study, based on coherence analysis method,
      we process the acquisition signals which consist of 9 channel EEG signal from
      motor cortex and 4 channel EMG signal from forearm, by using 4 groups of hand
      motions in the healthy subjects, including flexor digitorum, extensor digitorum,
      wrist flexion, and wrist extension. The results showed that in the beta-band, the
      coherence coefficients between C3 and flexor digitorum (FD) was greater than
      extensor digitorum (ED) in the right hand flexor digitorum movement; the
      coherence coefficients between C3 and ED was greater than FD in the right hand
      extensor digitorum movement; the coherence coefficients between C3 and flexor
      carpi ulnaris (FCU) was greater than extensor carpi radialis (ECR) in the right
      hand wrist flexion movement; the coherence coefficients between C3 and ECR was
      greater than FCU in the right hand wrist extension movement. This analysis
      provides experimental basis to explore the information decoding of hand motion
      based on corticomuscular coherence (CMC).

PMID- 25764705
TI  - [A wireless smart home system based on brain-computer interface of steady state
      visual evoked potential].
AB  - Brain-computer interface (BCI) system is a system that achieves communication and
      control among humans and computers and other electronic equipment with the
      electroencephalogram (EEG) signals. This paper describes the working theory of
      the wireless smart home system based on the BCI technology. We started to get the
      steady-state visual evoked potential (SSVEP) using the single chip microcomputer
      and the visual stimulation which composed by LED lamp to stimulate human eyes.
      Then, through building the power spectral transformation on the LabVIEW platform,
      we processed timely those EEG signals under different frequency stimulation so as
      to transfer them to different instructions. Those instructions could be received
      by the wireless transceiver equipment to control the household appliances and to
      achieve the intelligent control towards the specified devices. The experimental
      results showed that the correct rate for the 10 subjects reached 100%, and the
      control time of average single device was 4 seconds, thus this design could
      totally achieve the original purpose of smart home system.

PMID- 25764706
TI  - [Analysis of corticomuscular coherence during rehabilitation exercises after
      stroke].
AB  - To better evaluate neuromuscular function of patients with stroke related motor
      dysfunction, we proposed an effective corticomuscular coherence analysis and
      coherent significant judgment method. Firstly, the related functional frequency
      bands in the electroencephalogram (EEG) were extracted via wavelet decomposition.
      Secondly, coherence were analysed between surface electromyography (sEMG) and sub
      bands extracted from EEG. Further more, a coherent significant indicator was
      defined to quantitatively describe the similarity in certain frequency domain and
      phase lock activity between EEG and sEMG. Through the analysis of corticomuscular
      coherence during knee flexion-extension of stroke patients and healthy controls,
      we found that the stroke patients exhibited significantly lower gamma-band
      corticomuscular coherence in performing the task with their affected leg, and
      there was no statistically significant difference between their unaffected lag
      and the healthy controls, but with the rehabilitation training, the bilateral
      difference of corticomuscular coherence in patients decreased gradually.

PMID- 25764707
TI  - [Effect of different backpack loads on physiological parame ters in walking].
AB  - This study investigated the effect of prolonged walking with load carriage on
      body posture, muscle fatigue, heart rate and blood pressure of the tested
      subjects. Ten healthy volunteers performed 30 min walking trials on treadmill
      (speed = 1.1 m/s) with different backpack loads [0% body weight (BW), 10% BW, 15%
      BW and 20% BW]. The change of body posture, muscle fatigue, heart rate and blood
      pressure before and after walking and the recovery of muscle fatigue during the
      rest time (0, 5, 10 and 15 min) were collected using the Bortec AMT-8 and the NDI
      Optotrak Certus. Results showed that the forward trunk and head angle, muscle
      fatigue, heart rate and blood pressure increased with the increasing backpack
      loads and bearing time. With the 20% BW load, the forward angle, muscle fatigue
      and systolic pressure were significantly higher than with lighter weights. No
      significantly increased heart rate and diastolic pressure were found. Decreased
      muscle fatigue was found after removing the backpack in each load trial. But the
      recovery of the person with 20% BW load was slower than that of 0% BW, 10% BW and
      15% BW. These findings indicated that the upper limit of backpack loads for
      college-aged students should be between 15% BW and 20% BW according to muscle
      fatigue and forward angle. It is suggested that backpack loads should be
      restricted to no more than 15% BW for walks of up to 30 min duration to avoid
      irreversible muscle fatigue.

PMID- 25764708
TI  - [Experimental research of gaits based on young plantar pressure test].
AB  - The present paper is to study the center line of the plantar pressure of normal
      young people, and to find the relation between center line of the plantar
      pressure and gait stability and balance. The paper gives the testing principle
      and calculating methods for geometric center of plantar pressure distribution and
      the center of pressure due to the techniques of footprint frame. The calculating
      formulas in both x direction and y direction are also deduced in the paper. In
      the experiments carried out in our laboratory, the gait parameters of 131 young
      subjects walking as usual speed were acquired, and 14 young subjects of the total
      were specially analyzed. We then provided reference data for the walking gait
      database of young people, including time parameters, space parameters and plantar
      pressure parameters. We also obtained the line of geometry center and pressure
      center under the foot. We found that the differences existed in normal people's
      geometric center line and the pressure center line. The center of pressure
      trajectory revealed foot movement stability. The length and lateral changes of
      the center line of the plantar pressure could be applied to analysis of the
      plantar pressure of all kinds of people. The results in this paper are useful in
      clinical foot disease diagnosis and evaluation of surgical effect.

PMID- 25764709
TI  - [Design and implementation of the pulse wave generator with field programmable
      gate array based on windkessel model].
AB  - Pulse waves contain rich physiological and pathological information of the human
      vascular system. The pulse wave diagnosis systems are very helpful for the
      clinical diagnosis and treatment of cardiovascular diseases. Accurate pulse
      waveform is necessary to evaluate the performances of the pulse wave equipment.
      However, it is difficult to obtain accurate pulse waveform due to several kinds
      of physiological and pathological conditions for testing and maintaining the
      pulse wave acquisition devices. A pulse wave generator was designed and
      implemented in the present study for this application. The blood flow in the
      vessel was simulated by modeling the cardiovascular system with windkessel model.
      Pulse waves can be generated based on the vascular systems with four kinds of
      resistance. Some functional models such as setting up noise types and signal
      noise ratio (SNR) values were also added in the designed generator. With the need
      of portability, high speed dynamic response, scalability and low power
      consumption for the system, field programmable gate array (FPGA) was chosen as
      hardware platform, and almost all the works, such as developing an algorithm for
      pulse waveform and interfacing with memory and liquid crystal display (LCD), were
      implemented under the flow of system on a programmable chip (SOPC) development.
      When users input in the key parameters through LCD and touch screen, the
      corresponding pulse wave will be displayed on the LCD and the desired pulse
      waveform can be accessed from the analog output channel as well. The structure of
      the designed pulse wave generator is simple and it can provide accurate solutions
      for studying and teaching pulse waves and the detection of the equipments for
      acquisition and diagnosis of pulse wave.

PMID- 25764710
TI  - [Finite-element investigation on center of resistance of maxillary anterior
      teeth].
AB  - A three-dimensional finite element model of premaxillary bone and anterior teeth
      was established with ANSYS 13.0. The anterior teeth were fixed with strong
      stainless labial archwire and lingual frame. In the horizontal loading
      experiments, a horizontal retraction force of 1.5 N was applied bilaterally to
      the segment through hooks at the same height between 7 and 21 mm from the incisal
      edge of central incisor; in vertical loading experiments, a vertical intrusion
      force of 1.5 N was applied at the midline of lingual frame with distance between
      4 and 16 mm from the incisal edge of central incisor. After loading, solution was
      done and displacement and maximum principle stress were calculated. After
      horizontal loading, lingual displacement and stress in periodontal membrane (PDM)
      was most homogeneous when the traction force was 14 mm from the edge of central
      incisor; after vertical loading, intrusive displacement and stress in PDM were
      most homogeneous when the traction force was 12 mm from the incisal edge of
      central incisor. The results of this study suggested that the location of center
      of resistance (CRe) of six maxillary anterior teeth is about 14 mm gingivally and
      12 mm lingually to incisal edge of central incisor. The location can provide
      evidence for theoretical and clinical study in orthodontics.

PMID- 25764711
TI  - [Tumor segmentation of brain MRI with adaptive bandwidth mean shift].
AB  - In order to get the adaptive bandwidth of mean shift to make the tumor
      segmentation of brain magnetic resonance imaging (MRI) to be more accurate, we in
      this paper present an advanced mean shift method. Firstly, we made use of the
      space characteristics of brain image to eliminate the impact on segmentation of
      skull; and then, based on the characteristics of spatial agglomeration of
      different tissues of brain (includes tumor), we applied edge points to get the
      optimal initial mean value and the respectively adaptive bandwidth, in order to
      improve the accuracy of tumor segmentation. The results of experiment showed
      that, contrast to the fixed bandwidth mean shift method, the method in this paper
      could segment the tumor more accurately.

PMID- 25764712
TI  - [Respiratory motion correction in positron emission tomography imaging using
      elastic registration based on sinogram data].
AB  - In the process of positron emission tomography (PET) data acquiring, respiratory
      motion reduces the quality of PET imaging. In this paper, we present a correction
      method using three level grids B-spline elastic method to correct denoised and
      reorganized sinograms for respiratory motion correction. Using GATE simulates
      NCAT respiratory motion model to generate raw data which are used in experiment,
      the experiment results showed a significantly improved respiratory image with
      higher quality of PET, and the motion blur and structural information were fixed.
      The results proved the method of this paper would be effective for the elastic
      registration.

PMID- 25764713
TI  - [A fast iterative reconstruction algorithm of sparse angular CT based on the
      selective total variation].
AB  - Aiming at the problem of high-quality image reconstruction from projection data
      at sparse angular views, we proposed an improved fast iterative reconstruction
      algorithm based on the minimization of selective image total variation (TV). The
      new reconstruction scheme consists of two components. Firstly, the algebraic
      reconstruction technique (ART) algorithm was adopted to reconstruct image that
      met the identity and non-negativity of projection data, and then, secondly, the
      selective TV minimization was used to modify the above image. Two phases were
      alternated until it met the convergence criteria. In order to further speed up
      the convergence of the algorithm, we applied a fast convergence technology in the
      iterative process. Experiments on simulated Shepp-Logan phantom were carried out.
      The results demonstrated that the new method not only improved image
      reconstruction quality and protected the edge of the image characteristics, but
      also improved the convergence speed of the iterative reconstruction
      significantly.

PMID- 25764714
TI  - [An algorithm for separating overlapped protein spots based on valley
      characteristics].
AB  - To separate the overlapped protein spots in two-dimensional gel electrophoresis
      (2-DE) images, we proposed an auto-separating algorithm based on valley
      characteristics. Firstly, the marker-controlled watershed algorithm was used to
      detect the initial outlines of the object regions. Secondly, medial axis
      transform and hierarchical branch pruning method were applied to the main
      skeletons of the object regions, and each main skeleton was fitted into line
      segments to describe the overlap directions. Then, the 3-dimensional model of the
      object region was scanned on the normal planes of the line segments to find the
      valley locations. And finally, a validation model was adopted to construct
      separation lines. The experiments on 2 real scanned 2-DE images showed that the
      true overlap separate (TOSs) were 78.95% and 85.71%, respectively. The results
      indicated that the proposed algorithm was better than the existing algorithms and
      could be used in engineering practice.

PMID- 25764715
TI  - [Development of RF coil of permanent magnet mini-magnetic resonance imager and
      mouse imaging experiments].
AB  - In the development of radio frequency (RF) coils for better quality of the mini
      type permanent magnetic resonance imager for using in the small animal imaging,
      the solenoid RF coil has a special advantage for permanent magnetic system based
      on analyses of various types.of RF coils. However, it is not satisfied for
      imaging if the RF coils are directly used. By theoretical analyses of the
      magnetic field properties produced from the solenoid coil, the research direction
      was determined by careful studies to raise further the uniformity of the magnetic
      field coil, receiving coil sensitivity for signals and signal-to-noise ratio
      (SNR). The method had certain advantages and avoided some shortcomings of the
      other different coil types, such as, birdcage coil, saddle shaped coil and phased
      array coil by using the alloy materials (from our own patent). The RF coils were
      designed, developed and made for keeled applicable to permanent magnet-type
      magnetic resonance imager, multi-coil combination-type, single-channel overall RF
      receiving coil, and applied for a patent. Mounted on three instruments (25 mm
      aperture, with main magnetic field strength of 0.5 T or 1.5 T, and 50 mm
      aperture, with main magnetic field strength of 0.48 T), we performed experiments
      with mice, rats, and nude mice bearing tumors. The experimental results indicated
      that the RF receiving coil was fully applicable to the permanent magnet-type
      imaging system.

PMID- 25764716
TI  - [Bi-modality image classification based on independent component analysis].
AB  - We in the present research proposed a classification method that applied infomax
      independent component analysis (ICA) to respectively extract single modality
      features of structural magnetic resonance imaging (sMRI) and positron emission
      tomography (PET). And then we combined these two features by using a method of
      weight combination. We found that the present method was able to improve the
      accurate diagnosis of Alzheimer's disease (AD) and mild cognitive impairment
      (MCI). Compared AD to healthy controls (HC): the study achieved a classification
      accuracy of 93.75%, with a sensitivity of 100% and a specificity of 87.64%.
      Compared MCI to HC: classification accuracy was 89.35%, with a sensitivity of
      81.85% and a specificity of 99.36%. The experimental results showed that the bi
      modality method performed better than the individual modality in comparison to
      classification accuracy.

PMID- 25764717
TI  - [Influence of pivot distance on the performance of a mechanic heart valve].
AB  - Based on the analysis of the influence of the valve pivot distance on the
      performance of mechanical heart valve (MHV), such as the valve opening and
      closing features, flow field characteristics and the valve assembly properties,
      value constraints of the valve pivot distance were established, and the
      reasonable valve was obtained by means of the finite element method. It can be
      shown that the central flow characteristics of the valve could be enhanced with
      the increasing of the ratio of pivot distance to valve inner diameter, but the
      plastic deformation of the ring could be liable to occur in the MHV assembly
      process. It is proved that the valve of specifications can be designed in similar
      ratio of pivot distance to valve inner diameter according to the result of the
      valve performance experiment.

PMID- 25764718
TI  - [Effects of sintered bone modified with surface mineralization/P24 peptide
      composite biomaterial on the adhesion, proliferation and osteodifferentiation of
      MC3T3-E1 cells].
AB  - In the present research, the effects of sintered bone modified with surface
      mineralization/P24 peptide composite biomaterials on the adhesion, proliferation
      and osteodifferentiation of MC3T3-E1 cells were investigated. The experiments
      were divided into three groups due to biomaterials used: Group A (composite
      materials of sintered bone modified with surface mineralization and P24, a
      peptide of bone morphogenetic protein-2); Group B (sintered bone modified with
      surface mineralization) and Group C (sintered bone only). The three groups were
      observed by scanning electron microscopy (SEM) before the experiments,
      respectively. Then MC3T3-E1 cells were cultured on the surfaces of the three
      kinds of material, respectively. The cell adhesion rate was assessed by
      precipitation method. The proliferative ability of MC3T3-E1 cells were measured
      with MTT assay. And the ALP staining and measurement of alkaline phosphatase
      (ALP) activity were performed to assess the differentiation of cells into
      osteoblasts. The SEM results showed that the materials in the three groups
      retained the natural pore structure and the pore sizes were in the range between
      200-850 MUm. The adhesive ratio measurements and MTT assay suggested that
      adhesion and proliferation of MC3T3-E1 cells in Group A were much higher than
      those in Group B and Group C (P < 0.05). The ALP staining and ALP activity of
      MC3T3-E1 cells in Group A were significantly higher than those in Group B and
      Group C (P < 0.05). The sintered bone modified with surface mineralization/P24
      composite material was confirmed to improve the adhesion rate and proliferation
      and osteodifferentiation of MC3T3-E1 cells, and maintained their morphology.

PMID- 25764719
TI  - [Cytotoxicity of a new type silicone rubber for maxillofacial prosthesis: an in
      vitro evaluation].
AB  - This study evaluated the cytotoxicity of a new type silicone rubber for
      maxillofacial prosthesis, which was developed by the present authors. According
      to the GB/T16886. 5- 2003, the samples were prepared and tested with cell
      counting kit-8 (CCK-8) assay, the relative growth rate (RGR) was calculated, and
      morphology of L929 cells were observed by scanning electron microscope and phase
      contrast microscope. The results showed that RGR of L929 cells were 91.65% (24
      h), 87.03% (48 h), 87.30% (72 h), respectively, and the level of cytotoxicity was
      grade 1. The L929 cells showed typical fusiform shape and their morphology did
      not changed significantly after 24 h, 48 h and 72 h. These data indicated that
      the newly-developed silicone rubber material, as a maxillofacial prosthesis
      material, should be a safe biomaterial.

PMID- 25764720
TI  - [Research on magnetic coupling centrifugal blood pump control based on a self
      tuning fuzzy PI algorithm].
AB  - The purpose of this paper is to report the research and design of control system
      of magnetic coupling centrifugal blood pump in our laboratory, and to briefly
      describe the structure of the magnetic coupling centrifugal blood pump and
      principles of the body circulation model. The performance of blood pump is not
      only related to materials and structure, but also depends on the control
      algorithm. We studied the algorithm about motor current double-loop control for
      brushless DC motor. In order to make the algorithm adjust parameter change in
      different situations, we used the self-tuning fuzzy PI control algorithm and gave
      the details about how to design fuzzy rules. We mainly used Matlab Simulink to
      simulate the motor control system to test the performance of algorithm, and
      briefly introduced how to implement these algorithms in hardware system. Finally,
      by building the platform and conducting experiments, we proved that self-tuning
      fuzzy PI control algorithm could greatly improve both dynamic and static
      performance of blood pump and make the motor speed and the blood pump flow stable
      and adjustable.

PMID- 25764721
TI  - [Numerical simulation and optimization research of needle parameters in vial
      washing machine].
AB  - According to the working principle of vertical ultrasonic vial washing machine,
      receiving respective force of small water droplets on the inside wall of vials
      and the minimum air velocity of blowing off water droplets can be obtained based
      on the analysis of water-droplet-related parameters. The inside wall model of 7
      mL vial created by GAMBIT was divided into fine grids. Then the Realizable k
      epsilon Two Equation Turbulence Model was adopted and the flow field of vial by
      FLUENT software was simulated when air was flushing inside the wall. In that
      case, the optimal position, inner diameter and the corresponding minimum air
      velocity of needle can be acquired to meet the needs of vial washing machine
      applied to 7 mL vial.

PMID- 25764722
TI  - [An improved software design of ultrasound bone densitometer].
AB  - In order to meet the requirements of ultrasound bone density measurement, we
      proposed a software solution to improve the accuracy and speed of measurement of
      bone mineral density of the ultrasound bone densitometer. We used a high-speed
      USB interface chip FT232H, along with a high-speed AD converter chip to calculate
      speed of sound (SOS), broadband ultrasound attenuation (BUA ) and other bone
      density parameters in the PC software. This solution improved the accuracy of the
      measurement data, reduced the measurement time and increased the quality of the
      displayed image. It is well concluded that the new software can greatly improve
      the accuracy and transmission speed of bone density measurement data through a
      high-speed USB interface and a software data processing technology.

PMID- 25764723
TI  - [Study of the RNA secondary structure prediction].
AB  - This paper proposes algorithm in predicting the RNA secondary structure that
      combines several sequence comparisons, searches the eigenvalue for subsequence
      division with dynamic programing, utilizing the minimum free energy method.
      Moreover, the paper assesses the results derived from this new algorithm based on
      base-pairs distance, climbing distance and morphology distance. The paper also
      compares the assessment result and the prediction results of different prediction
      tools, and analyzes the advantages of the new method and its improvement
      direction.

PMID- 25764724
TI  - [Experimental study on electrical impedance properties of human hepatoma cells].
AB  - The AC impedance of human hepatoma SMMC-7721 cells were measured in our
      laboratory by Agilent 4294A impedance analyzer in the frequency range of 0.01-100
      MHz. And then the effect of hematocrit on electrical impedance characteristics of
      hepatoma cells was observed by electrical impedance spectroscopy, Bode diagram,
      Nyquist diagram and Nichols diagram. The results showed that firstly, there is a
      frequency dependence, i.e., the increment of real part and the imaginary part of
      complex electrical impedance (deltaZ', deltaZ"), the increment of the amplitude
      modulus of complex electrical impedance (delta[Z *]) and phase angle (deltatheta)
      were all changed with the increasing frequency. Secondly, it showed cell volume
      fraction (CVF) dependence, i. e. , the increment of low-frequency limit
      (deltaZ'0, delta[Z*] 0), peak (deltaZ"(p), deltatheta(p)), area and radius
      (Nyquist diagram, Nichols diagram) were all increased along with the electric
      field frequency. Thirdly, there was the presence of two characteristic
      frequencies: the first characteristic frequency (f(c1)) and the second
      characteristic frequency (f(c2)), which were originated respectively in the
      polarization effects of two interfaces that the cell membrane and extracellular
      fluid, cell membrane and cytoplasm. A conclusion can be drawn that the electrical
      impedance spectroscopy is able to be used to observe the electrical
      characteristics of human hepatoma cells, and therefore this method can be used to
      investigate the electrophysiological mechanisms of liver cancer cells, and
      provide research tools and observation parameters, and it also has important
      theoretical value and potential applications for screening anticancer drugs.

PMID- 25764725
TI  - [Comparison of cell elasticity analysis methods based on atomic force microscopy
      indentation].
AB  - In order to investigate in greater detail the two methods based on Hertz model
      for analyzing force-distance curve obtained by atomic force microscopy, we
      acquired the force-distance curves of Hela and MCF-7 cells by atomic force
      microscopy (AFM) indentation in this study. After the determination of contact
      point, Young's modulus in different indentation depth were calculated with two
      analysis methods of "two point" and "slope fitting". The results showed that the
      Young's modulus of Hela cell was higher than that of MCF-7 cell,which is in
      accordance with the F-actin distribution of the two types of cell. We found that
      the Young's modulus of the cells was decreased with increasing indentation depth
      and the curve trends by "slope fitting". This indicated that the "slope fitting"
      method could reduce the error caused by the miscalculation of contact point. The
      purpose of this study was to provide a guidance for researcher to choose an
      appropriate method for analyzing AFM indentation force-distance curve.

PMID- 25764726
TI  - [Study of TGF-beta/Smad3 signal pathway using the technology of flurorescence
      resonance energy transfer].
AB  - The transforming growth factor-beta1 (TGF-beta1)/Smad3 signal pathway is related
      to mutiple physiological and pathological generation mechanism of human being. Up
      to date, however, the spacial and time information on the phosphorylated Smad3 is
      still unclear. In this study, the process of Smad3 phosphorylation was observed
      under the physiological state in the living cells. Firstly, the ECFP-Smad3
      Citrine (Smad3 biosensor) fusion protein expression vector was constructed and
      identified. Then the Smad3 biosensor was transfected into 293T cells. The
      transfection efficiency and the expressions of fusion proteins were observed in
      24 hours. Thirdly, Smad3 biosensor flurorescence resonance energy transfer (FRET)
      was observed with the inversion fluorescence microscope and measured by the
      MetaFlour FRET 4. 6 software. Smad3 biosensor transfection efficiency was nearly
      40% and the fusion protein was seen under the fluorescence microscope. The FRET
      ratio of Smad3 biosensor in living 293T cells was decreased after 10 minutes
      incubation with the ligand of TGF-beta1. The period of decreasing CFP and
      enhancing Citrine signals was about 300 seconds. With the technology of FRET, the
      TGF-beta1/Smad3 signal pathway could be real time monitored dynamically under the
      physiological condition in living cells.

PMID- 25764727
TI  - [Establishment of human neuroblastoma SH-SY5Y cell line stably silencing
      beclin1].
AB  - The pGenesil-1-Beclin1 eukaryotic expression vectors were constructed to
      establish an SH-SY5Y cell line stably expressing shRNA-Beclin1. The shRNA was
      connected to pGenesil-1 to construct the recombinant plasmid pGenesil-1-Beclin1,
      which was transformed into JM109 E. coli. Positive clones were identified by
      digestion with restriction endonuclease and DNA sequencing. SH-SY5Y cells were
      cultured by the conventional method. The pGenesil-1-Beclin1 and pGenesil-1
      plasmids were transfected into SH-SY5Ycells, and the cells were screened by G418
      until the stable G418-resistant monoclonal cells were acquired. Beclin1 mRNA and
      Beclin1 protein were detected by RT-PCR and Western blot analysis respectively.
      The results of restriction endonuclease analysis and DNA sequencing confirmed the
      correct construction of the eukaryotic expression vector pGenesil-1-Beclin1. Two
      SH-SY5Y transfected cell lines were successfully selected. Compared with the
      control group, RT-PCR and Western blot showed that the expression of Beclin1 mRNA
      and protein were down regulated 71.28% +/- 1.45% (P < 0.05)and 75.50% +/- 2.63%
      (P < 0.05), respectively. The results indicated that the eukaryotic expression
      vector pGenesil-1-Beclin1 was successfully constructed and the SH-SYSY cell lines
      with inhibited Beclin1 expression were established. It provides a useful cell
      model for studying the biological function of Beclin1.

PMID- 25764728
TI  - [Preparation and identification of recombinant sarcosine oxidase].
AB  - An important index determination for clinical diagnosis of renal function is to
      assay the creatinine concentration in serum. In the analytical process applied
      with coupled-enzyme, the quality control of sarcosine oxidase (SOX) as a key
      enzyme is the first problem to be solved. In order to establish an efficient and
      laboratory-scale production of SOX, the recombinant sarcosine oxidase (r-SOX)
      gene was a high-level expression in E. coli induced with lactose on a large-scale
      fermentation in 300 L fermenter. The results suggested that the biomass
      concentration reached OD600 of 22 and the expression of recombinant sarcosine
      oxidase in E. coli accounted for about 25% of total soluble protein in culture
      after fermentation. The cell-free extract obtained from high pressure homogenizer
      was processed by selective thermal denaturation and then purified with Ni
      Sepharose FF chromatography. The sarcosine oxidase with 97% purity, 25 U/mg
      specific activity and 92.4% activity recovery was obtained. The molecular weight
      with single peptide chain of 53 kD and 55 kD of recombinant sarcosine oxidase was
      assessed by SDS-PAGE in presence or absence of 2-mercaptoehanol and Sephacryl S
      200 chromatography. This sarcosine oxidase was found to be a conjugated protein,
      yellow enzyme, which combined with FAD as prosthetic group by covalent linkage.
      The contaminant of catalase was not detected in the sample pool of this enzyme.
      In addition, a further test to the thermal stability of sarcosine oxidase was
      done. According to the above results, the development and utilization of this
      enzyme has been set up on a reliable foundation.

PMID- 25764729
TI  - [Relationship between intermedin and atrial fibrosis in patients of hypertension
      combined with atrial fibrillation].
AB  - This study was aimed to evaluate the relationship between the changes of plasma
      intermedin (IMD) and atrial fibrosis in hypertensive patients with atrial
      fibrillation. During the period from 2010 to 2011, appropriate 150 subjects of
      out-patients (female 50%, male 50%) were selected in West China Hospital, Sichuan
      University, and were divided into three groups: the hypertension-only group, the
      hypertension combined with paroxysmal atrial fibrillation group and the
      hypertension combined with persistent atrial fibrillation group. Firstly, we
      collected the Physical examination results and medical history records of the
      patients. We then performed ultrasound cardiogram and blood biochemical tests on
      the patients. We also detected the plasma IMD and transforming growth factor
      beta1 (TGF-beta1) using ELISA. The results showed that compared with the
      hypertensive group, the plasma level of IMD, TGF-beta1 and left atrium director
      (LAD) in the hypertensive combined with atrial fibrillation group were higher
      significantly. Compared with the paroxymal atrial fibrillation group, the levels
      of IMD, TGF-beta1 and LAD were higher significantly in persistent atrial
      fibrillation group. Analysis of correlation and partial correlation showed that
      IMD was positively correlated with TGF-p1 (r=0.51, P<0. 001), IMD was positively
      correlated with LAD(r=0.59, P< 0.001), and TGF-beta1 was positively correlated
      with LAD (r = 0.57, P < 0.001). The results suggest that IMD might suppress the
      pathophysiological process of atrial fibrillation.

PMID- 25764730
TI  - [Early clinical effect of intervertebral fusion of lumbar degenerative disease
      using nano-hydroxyapatite/polyamide 66 intervertebral fusion cage].
AB  - The present study is aimed to investigate the early clinical effects of nano
      hydroxyapatite/polyamide 66 intervertebral fusion cage (n-HA/PA66 cage) for the
      treatment of lumbar degenerative diseases. We selected 27 patients with lumbar
      degenerative diseases who were managed by posterior decompression or reset
      operation combined with n-HA/PA66 cage intervertebral fusion and internal
      fixation from August 2010 to January 2012. The oswestry disability index (ODI),
      low back and leg pain visual analogue score (VAS), and intervertebral height (IH)
      were evaluated at preoperation, 1 week postoperation and the last follow-up
      period, respectively. Intervertebral bony fusion was evaluated at the last follow
      up time. The patients were followed up for 12-24 months (averaged 19 months). The
      ODI, VAS and IH were significantly improved at 1 week postoperation and the last
      follow-up time compared with those at preoperative period (P < 0.05). But there
      was no significant difference between 1 week postoperative and the last follow-up
      time (P < 0.05). Brantigan's standard was used to evaluate fusion at the last
      follow-up time. There were 19 patients with grade 5 fusion, 8 with grade 4
      fusion, with a fusion rate of 100%, and none with grade 1-3 fusions. There was no
      cage translocation and internal fixation breakage. These results suggested that n
      HA/PA66 cage was an ideal biological material in the posterior lumbar interbody
      fusion and internal fixation operation for treatment of lumbar degenerative
      diseases. It can effectively maintain the intervertebral height and keep a high
      rate of bony fusion. The early clinical effect has been satisfactory.

PMID- 25764731
TI  - [Effects of ultrasound-guided stellate ganglion block on cerebral oxygen
      metabolism and postoperative cognitive dysfunction in the elderly].
AB  - To observe the effects of ultrasound-guided stellate ganglion block (SGB) on
      cerebral oxygen metabolism and postoperative cognitive dysfunction (POCD) of
      elderly patients, we collected 80 elderly patients undergoing selective coronary
      artery bypass graft under cardiopulmonary bypass. The Mini Mental State
      Examination (MMSE) was applied to test the cognitive function. The SjvO2, Da-jvO2
      and CEO2 were used for the analysis of the cerebral oxygen metabolism. We found
      that POCD was related to disequilibrium of cerebral oxygen metabolism. Ultrasound
      guided SGB before surgery reduced the incidence of POCD because of the
      improvement of cerebral oxygen metabolism.

PMID- 25764732
TI  - [Early abnormalities of kidneys in patients with primary hypertension by 3.0 T
      functional magnetic resonance imaging].
AB  - This study aims to detect early changes of kidney in patients with primary
      hypertension by 3.0 T functional magnetic resonance imaging (fMRI). 26 patients
      with primary hypertension (hypertension group) and 33 healthy volunteers (control
      group) underwent conventional and functional magnetic resonance scans, which
      included blood oxygen level-dependent (BOLD) MRI, diffusion weighted imaging
      (DWI) and diffusion tensor imaging (DTI). We measured renal cortical thickness
      (CT), parenchymal thickness (PT), and functional values of renal cortex and
      medulla including R2* value, apparent diffusion coefficient (ADC) value and
      fractional anisotropy (FA) value in each group, and then calculated the
      cortical/parenchymal thickness ratio (CPR). Compared with those in the control
      group, CT and CPR in hypertension group were larger (P < 0.01), cortical and
      medullar R2* values increased (P < 0.01) whereas medullar FA values decreased (P
      < 0.05). It could be well concluded that noninvasive 3.0 T functional MRI would
      have important clinical significance in identifying early abnormalities of kidney
      in hypertension patients.

PMID- 25764733
TI  - [Application of computer-aided diagnosis in early detection of pulmonary nodules
      based on digital chest radiograph].
AB  - This study aims to explore the clinical value of the computer-aided diagnosis
      (CAD) system for early detection of the pulmonary nodules on digital chest X-ray.
      A total of 100 cases of digital chest radiographs with pulmonary nodules of 5-20
      mm diameter were selected from Pictures Archiving and Communication System (PACS)
      database in West China Hospital of Sichuan University were enrolled into trial
      group, and other 200 chest radiographs without pulmonary nodules as control
      group. All cases were confirmed by CT examination. Firstly, these cases were
      diagnosed by 5 different-seniority doctors without CAD, and after three months,
      these cases were re-diagnosed by the 5 doctors with CAD. Subsequently, the
      diagnostic results were analyzed by using SPSS statistical methods. The results
      showed that the sensitivity and specificity for detecting pulmonary nodules
      tended to be improved by using the CAD system, especially for specificity, but
      there was no significant difference before and after using CAD system.

PMID- 25764734
TI  - [Application of free-form deformation algorithm in fast three-dimensional bone
      reconstruction].
AB  - This paper presents a unit free-form deformation (FFD) method applied to rapid
      three-dimensioanl (3D) bone reconstruction, which was based on traditional FFD.
      With the femur as an example, we reconstructed a 3D model of femur from two X-ray
      images and a standardized model by taking advantage of unit FFD algorithm. The X
      ray images and its parameters were taken by C-arm device. Those parameters and X
      ray contour are contributed to 3D reconstruction. The out contours of X-ray image
      and standard model were connected by point matching algorithm. The unit-FFD
      lattice was built to reconstruct standard model and finally made the contour of X
      ray image and standard model exactly the same. Experiments on shape accuracy,
      robustness and time consuming, carried out by 35 specimen from cadaver, showed
      that mean error of shape (0. 52 mm) and mean construction time (112 s) were lower
      than those using traditional method (0.7-2.6 mm, 8-20 min). The method proposed
      in this paper shows a good prospect in clinical application and related research.

PMID- 25764735
TI  - [Research on visualization of ultrasonic rhinitis therapeutic apparatus based on
      V4L2].
AB  - This paper reports the study and design of a visualization system of the
      ultrasonic rhinitis therapeutic apparatus with the function of endoscopic sinus.
      On Linux operating platform, we captured the video data of a video capture card
      that connected the endoscopic sinus using Video4Linux (V4L2) that was provided by
      the operating system. The video images were displayed by Qt. The visualization
      system solved the problem that the current ultrasonic rhinitis therapeutic
      apparatus had to rely on the large and expensive endoscopy equipment. And this
      simplified the doctors' operation, met the need of monitoring nasal cavity in the
      process of operating, greatly reduced the costs of treatment and would contribute
      to the promotion of the instrument. As a result, it has been tested that the
      nasal endoscopic image achieved by the system is clear and smooth, and fully meet
      the clinical needs of ultrasonic treatment of rhinitis.

PMID- 25764736
TI  - [Mental fatigue electroencephalogram signals analysis based on singular system].
AB  - In the present paper, the contribution of the largest principal component and the
      number of principal component needed for accumulative contribution 95% are
      selected as indices of electroencephalogram (EEG) in mental fatigue state in
      order to investigate the relationship between these parameters and mental
      fatigue. The experimental results showed that the contribution of the largest
      principal component of EEG signals increased in the prefrontal, frontal and
      central areas, while the number of principal component needed for accumulative
      contribution decreased by 95% with the increasing mental fatigue level. The
      parameters of singular system of EEG signals can be regarded as useful features
      for the estimation of mental fatigue and have larger application value in the
      study of mental fatigue.

PMID- 25764737
TI  - [Elastic registration method to compute deformation functions for mitral valve].
AB  - Mitral valve disease is one of the most popular heart valve diseases. Precise
      positioning and displaying of the valve characteristics is necessary for the
      minimally invasive mitral valve repairing procedures. This paper presents a multi
      resolution elastic registration method to compute the deformation functions
      constructed from cubic B-splines in three dimensional ultrasound images, in which
      the objective functional to be optimized was generated by maximum likelihood
      method based on the probabilistic distribution of the ultrasound speckle noise.
      The algorithm was then applied to register the mitral valve voxels. Numerical
      results proved the effectiveness of the algorithm.

PMID- 25764738
TI  - [Research on optimization of lower limb parameters of cardiopulmonary
      resuscitation simulation model based on genetic algorithm].
AB  - Sudden cardiac arrest is one of the critical clinical syndromes in emergency
      situations. A cardiopulmonary resuscitation (CPR) is a necessary curing means for
      those patients with sudden cardiac arrest. In order to simulate effectively the
      hemodynamic effects of human under AEI-CPR, which is active compression
      decompression CPR coupled with enhanced external counter-pulsation and
      inspiratory impedance threshold valve, and research physiological parameters of
      each part of lower limbs in more detail, a CPR simulation model established by
      Babbs was refined. The part of lower limbs was divided into iliac, thigh and
      calf, which had 15 physiological parameters. Then, these 15 physiological
      parameters based on genetic algorithm were optimized, and ideal simulation
      results were obtained finally.

PMID- 25764739
TI  - [Enhancement and assessment of the fundus image].
AB  - A new enhancement method is proposed based on the characteristics of fundus
      images in this paper. Firstly, top-hat transform is utilized to weaken the
      background. Secondly, contrast limited adaptive histogram equalization (CLAHE) is
      performed to improve the uneven illumination. Finally, two-dimensional matched
      filters are designed to further enhance the contrast between blood vessels and
      background. The algorithm was tested in DIARETDB0 databases and showed good
      applicability for both normal and pathological fundus images. A new no-reference
      image quality assessment method was used to evaluate the enhancement methods
      objectively. The results demonstrated that the proposed method could effectively
      weaken the background, increase contrast, enhance details in the fundus images
      and improve the image quality greatly.

PMID- 25764740
TI  - [A comparative study of pathological voice based on traditional acoustic
      characteristics and nonlinear features].
AB  - By analyzing the mechanism of pronunciation, traditional acoustic parameters,
      including fundamental frequency, Mel frequency cepstral coefficients (MFCC),
      linear prediction cepstrum coefficient (LPCC), frequency perturbation, amplitude
      perturbation, and nonlinear characteristic parameters, including entropy (sample
      entropy, fuzzy entropy, multi-scale entropy), box-counting dimension, intercept
      and Hurst, are extracted as feature vectors for identification of pathological
      voice. Seventy-eight normal voice samples and 73 pathological voice samples for
      /a/, and 78 normal samples and 80 pathological samples for /i/ are recognized
      based on support vector machine (SVM). The results showed that compared with
      traditional acoustic parameters, nonlinear characteristic parameters could be
      well used to distinguish between healthy and pathological voices, and the
      recognition rates for /a/ were all higher than those for /i/ except for multi
      scale entropy. That is why the /a/ sound data is used widely in related research
      at home and abroad for obtaining better identification of pathological voices.
      Adopting multi-scale entropy for /i/ could obtain higher recognition rate than
      /a/ between healthy and pathological samples, which may provide some useful
      inspiration for evaluating vocal compensatory function.

PMID- 25764741
TI  - [Recent progress of research and applications of fractal and its theories in
      medicine].
AB  - Fractal, a mathematics concept, is used to describe an image of self-similarity
      and scale invariance. Some organisms have been discovered with the fractal
      characteristics, such as cerebral cortex surface, retinal vessel structure,
      cardiovascular network, and trabecular bone, etc. It has been preliminarily
      confirmed that the three-dimensional structure of cells cultured in vitro could
      be significantly enhanced by bionic fractal surface. Moreover, fractal theory in
      clinical research will help early diagnosis and treatment of diseases, reducing
      the patient's pain and suffering. The development process of diseases in the
      human body can be expressed by the fractal theories parameter. It is of
      considerable significance to retrospectively review the preparation and
      application of fractal surface and its diagnostic value in medicine. This paper
      gives an application of fractal and its theories in the medical science, based on
      the research achievements in our laboratory.

PMID- 25764742
TI  - [Research status and development trends of the heart valve mechanical
      properties].
AB  - The study of mechanical properties on heart valves can provide an important
      theoretical basis for doctors to repair heart valves and prosthetic valve
      materials research. In this paper, we present the current status of the
      mechanical property study methods of heart valve, expound the methods and special
      requirements about uniaxial tensile test and biaxial tensile test of the heart
      valve, and further discuss several establishment methods of heart valve
      constitutive models. We also discuss the development trend of heart valve
      mechanics.

PMID- 25764743
TI  - [Research progress of cell sheet technology and its applications in tissue
      engineering and regenerative medicine].
AB  - Cell sheet engineering is an important technology to harvest the cultured cells
      in the form of confluent monolayers using a continuous culture method and a
      physical approach. Avoiding the use of enzymes, expended cells can be harvested
      together with endogenous extracellular matrix, cell-matrix contacts, and cell
      cell contacts. With high efficiency of cell loading ability and without using
      exogenous scaffolds, cell sheet engineering has several advantages over
      traditional tissue engineering methods. In this article, we give an overview on
      cell sheet technology about its applications in the filed of tissue regeneration,
      including the construction of soft tissues (corneal, mucous membrane, myocardium,
      blood vessel, pancreas islet, liver, bladder and skin) and hard tissues (bone,
      cartilage and tooth root). This techonoly is promising to provide a novel
      strategy for the development of tissue engineering and regenerative medicine. And
      further works should be carried out on the operability of this technology and its
      feasibility to construct thick tissues.

PMID- 25764744
TI  - [Molecular regulation of skeletal satellite cell's self-renewal].
AB  - Skeletal muscle possesses a remarkable ability for its regeneration and injured
      tissue repair. This ability depends on the activity and contributions of muscle
      satellite cells. Proliferating satellite cells, termed myogenic precursor cells
      or myoblasts, are activated and driven out of their quiescent state upon muscle
      injury. In this summary, we present a review to summarize the molecular
      regulation in skeletal satellite cells to light on the satellite cells' self
      renewal mechanism.

PMID- 25764745
TI  - [Advances in functional magnetic resonance imaging of liver fibrosis].
AB  - Early diagnosis and accurate stage of liver fibrosis are important for conducting
      the clinic therapy and assessing the therapeutic outcome. Functional magnetic
      resonance imaging (fMRI), as a noninvasive and effective method, plays an
      important role in diagnosis and stage of liver fibrosis. This review focuses on
      the advances in fMRI evaluation of liver fibrosis.

PMID- 25764746
TI  - [Research on medical data mining and its applications].
AB  - With the development of computer technology, medical data has developed from
      traditional paper pattern into electronic mode, which could effectively promote
      the medical development. This paper at first presents the status and
      characteristics of medical data mining. Then, it discusses the critical method of
      medical data mining in classification, clustering and prediction, respectively.
      The paper focuses on the application and assessment of five algorithms which are
      designed for medical data mining, including decision tree, cluster analysis,
      association rule, intelligent algorithm and the mix algorithm. Finally, this
      paper outlooks the data mining application in medical domain.

PMID- 25764747
TI  - [Surgical treatment of pituitary apoplexy through endoscopic endonasal
      transsphenoida].
AB  - OBJECTIVE: To evaluate the transsphenoidal endoscopic endonasal approach for the
      surgical treatment of pituitary apoplexy (PA). METHOD: A retrospective analysis
      was conducted over the clinical data of 42 pathologically diagnosed of PA after
      transsphenoidal endoscopic endonasal approach for the resection. CT scan, MRI
      scan and endocrinological examinations were performed in all case before
      operation. Glucocorticoids were used during perioperatve period. The
      postoperation symptoms and the results follow-up visit after operation were
      recorded. RESULT: The tumors were totally removed in 36 cases and subtotally
      removed in 6 cases. In follow-up period from half a year to 13 years, headaches
      were resolved in 100%, visual interference were resolved in 91.9%, pituitary
      dysfunction were resolved in 77.3%. Without operative death and serious
      complications. No patient recurred. CONCLUSION: We concluded that the
      transsphenoidal endoscopic endonasal approach is a safe, effective and
      microsurgery treatment of PA.

PMID- 25764748
TI  - [Analysis of factors of intracranial infection after transnasal endoscopic
      crannialbase approach].
AB  - OBJECTIVE: To analyze the factors of intracranial infection after transnasal
      endoscopic crannialbase approach. METHOD: Retrospective analysis of 346 patients
      of ransnasal endoscopic crannialbase approach, logistic regression analysis of
      the factors was carried out. RESULT: The total number of cases of postoperative
      infections were 19 cases in 346 patients, the infection rate was 5.49%. The
      cerebrospinal fluid rhinorrhea , the restitution of skull base, the history of
      crannialbase approach, the history of radiotherapy and diabetes were infection
      fators after transnasal endoscopic diabetes (P < 0.05), while sex,age,operative
      approach,the use of artificial material,longer application of antibiotics before
      or after operation,and the history of chemotherapy had no obvious effects (P >
      0.05). CONCLUSION: Intracranial infection after transnasal endoscopic the use of
      artificial material was affected by many factors. Much attention should be paid
      for the intracranial infection prevention.

PMID- 25764749
TI  - [Endoscopic endonasal approach resection for anterior skull base, pterygopalatine
      fossa and infratemporal fossa tumors: retrospective analysis of 73 patients].
AB  - OBJECTIVE: To summarize the clinical experience with endoscopic transnasal
      resection of nasal skull- base neoplasms, which involved anterior skull base,
      pterygopalatine fossa, nfratemporal fossa. METHOD: Clinical data from 73 patients
      performed on endoscopic transnasal resection of nasal skull-base neoplasms were
      analyzed retrospectively. RESULT: Total tumor removal was obtained in 54 cases,
      subtotal removal in 19 cases. In 16 cases of benign tumor, the postoperative
      survival rate was 100%; Malignancy in 57 cases, of which 16 patients were died,
      and half-year survival rate was 71.9%. CONCLUSION: Endoscopic endonasal approach
      be able to fully reveal and re- moval of lesions involving the anterior skull
      base, pterygopalatine fossa and infratemporal fossa. The approach is feasible and
      safe.

PMID- 25764750
TI  - [Transnasal endoscopic anatomy of the clivus and approaches consideration].
AB  - OBJECTIVE: In-depth understanding of endoscopic anatomy of the skull base is the
      cornerstone of the development of endoscopic endonasal skull base surgery. The
      purpose of this study is to explore the anatomical landmarks of the clivus for
      endoscopic endonasal skull base surgery. METHOD: Eight silicon-injected adult
      cadaveric heads (16 sides) were dissected performing endoscopic endonasal
      approach. The clivus and adjacent structures were exposed; and their anatomy
      shown in detail. High-quality pictures were produced. RESULT: The clivus was
      subdivided into the upper, the middle and the lower clivus. Extracranial soft
      tissue landmarks and bony landmarks were presented. Intradural landmarks of the
      upper clivus were the interpeduncular cistern, posterior cerebral artery,
      posterior communicating artery, superior cerebellar artery, cranial nerve III and
      cerebral peduncle; intradural landmarks of the middle clivus were the prepontine
      cistern, basilar artery, cranial nerve VI and pons; intradural landmarks of lower
      clivus were premedullary cistern, vertebral artery, cranial nerve XI and medulla
      oblongata. Surgical routes to the clivus were the upper clivus approach, middle
      clivus approach, lower clivus approach and panclival approach. CONCLUSION: An
      understanding of the complex anatomy of the clivus is paramount for surgically
      dealing with the disease involved clivus and adjacent region.

PMID- 25764751
TI  - [Anatomy and imaging study of a new upper-agger nasi pathway of frontal sinus
      surgery].
AB  - OBJECTIVE: To investigate the new surgical pathway of endoscopic frontal sinus
      surgery for frontal sinus lesions through the upper-agger nasi approach. METHOD:
      The computed tomography (CT) scans from 32 patients were collected and subjected
      to three-dimensional reconstruction by Mimics. The distance in sagittal planes
      from anterior ethmoid artery to midpoint of axilla and to skull base attachment
      at anterior middle turbinate was measured. The distance in coronal planes between
      the perpendicular plate of middle turbinate and the orbital lamina was also
      detected as well as the height of agger nasi. Three-dimensional structures of the
      frontal sinus and its surrounding cells was reconstructed by Sinuses Trachea I
      software. We integrated the CT scans and the above data for simulating surgical
      operation on cadaveric heads. RESULT: (1) Skull base attachment at anterior
      middle turbinate located at the anterior or posterior of aperture of frontal
      sinus. (2) The mean distance between anterior ethmoid artery and midpoint of
      axilla was (22.23 +/- 2.78) mm on the left side and (22.30 +/- 2.80) mm on right.
      The mean distance between anterior ethmoid artery and skull base attachment at
      anterior middle turbinate was (15.31 +/- 2.82) mm on left and (15.39 +/- 3.53) mm
      on right. The distance between perpendicular plate of middle turbinate and
      orbital lamina was (7.61 +/- 1.34) mm on left and (7.80 +/- 1.40) mm on right
      side. The height of the agger nasi was (8.33 +/- 2.14) mm on left and (8.00 +/-
      2.57) mm on right. There was no statistical difference in the above data between
      left and right side (P > 0.05). (3) The visible three-dimensional structure
      showed that skull base attachment at the anterior middle turbinate was closely
      adjoined the aperture of frontal sinus, the space between sub-outer side of the
      attachment and orbital lamina, above the agger nasi cell or the upper area of the
      agger nasi cell was solely cell structures. CONCLUSION: Endoscopic frontal sinus
      surgery for frontal sinus lesions through the upper-agger nasi approach was
      practicable to solitary frontal sinus lesions and to solve the complex frontal
      sinus or frontal recess lesions by flexible operation according to the feature of
      the lesions.

PMID- 25764752
TI  - [Clinical analysis of 23 primary sinonasal malignant melanoma].
AB  - OBJECTIVE: To review the pathological and clinical features and treatment of
      sinonasal malignant melanoma. METHOD: A retrospective analysis of 23 cases of
      sinonasal malignant melanoma. All the patients were conformed by histopathology,
      the most common symptoms were nasal obstruction and epistexis. Eight cases were
      treated with surgery, 8 with surgery and radiotherapy, 5 with surgery and
      chemotherapy, 2 with surgery and ra- diotherapy plus chemotherapy. RESULT: Twenty
      patients were followed up, the survival rates of 3 and 5 years were 50% (10/20)
      and 35% (7/20), respectively. CONCLUSION: Sinonasal malignant melanoma has an
      aggressive behavior and easy recurrence and poor prognosis. Early diagnosis and
      reasonable treatment can increase the survival rate of the disease.

PMID- 25764753
TI  - [Sinonasal teratocarcinosarcoma: clinicopathologic study and analysis].
AB  - OBJECTIVE: To study the clinicopathologic features, immunophenotype, diagnosis
      and differential diagnosis of Sinonasal teratocarcinosarcoma (SNTCS). METHOD: The
      clinical findings, morphologic features and immunohistochemical markers in one
      case of SNTCS were studied, and the relevant literatures were reviewed. RESULT:
      The Tumor tissue is composed of three layers, with mature and immature squamous
      epithelium nests, neural epithelial cells and olfactory neuroblastoma-like cells
      derived of ectoderm; Sarcomatoid components and bone tissue derived of mesoderm;
      The glandular and tubular structures part of which is adenocarcinoma and
      respiratory epithelium derived of endoderm; The fetal clear cell squamous
      epithelium is typical. In addition, diffuse large cytoplasm-with high light and
      cytoplasm with dark light has no obviously boundery. Immunohistochemical staining
      showed immune markers of different germ layers corresponding, squamous
      epithelium, glandular epithelium and respiratory epithelium were positive for CK
      and EMA, neural epithelial cells and olfactory neuroblastoma-like cells were
      positive for S-100, NSE and Syn, sarcomatoid area was positive for Vim, light dye
      area was positive for Vim, CD99 and CK, dark area was positive for NSE and GFAP.
      CONCLUSION: SNTCS is a rare malignant tumor with the features of teratoma and
      carcinosarcoma, its histopathological and immunohistochemical features were
      typical, should be more drawn and sliced to avoid misdiagnosis and missed
      diagnosis.

PMID- 25764754
TI  - [Endoscopic resection of benign fibro-osseous lesions of naso-sinuses with
      different surgical choice].
AB  - OBJECTIVE: To explore and discuss the characteristics of benign fibro-osseous
      lesion of naso-sinuses and the features and indications of different surgical
      choice with endoscope. METHOD: Fourteen patients with benign fibro-osseous lesion
      of naso-sinuses were treated through endoscopic surgery, of which 9 cases
      underwent endonasal endoscopic surgery simply, 2 cases were operated with a
      superciliary arch incision through endoscope, 1 case underwent endoscopic
      caldwell-luc' surgery, 1 case was operated with endoscopic surgery through
      frontal recess of tears, and 1 case was operated with Draf II surgery under
      endoscope. RESULT: In all of patients, 2 cases relapsed, 2 cases had residual
      lesions, 4 cases had complications including numbness and scar of incision, no
      relapse and no complications in other 6 cases. CONCLUSION: Endoscopic resection
      of benign fibro-osseous lesion of naso-sinuses with different surgical choice was
      of special advantages, but the exactly indications, relapse rate and
      complications should be observed and reckoned deeply.

PMID- 25764755
TI  - [Systemic complications of functional endoscopic sinus surgery in patients with
      chronic rhinosinusitis].
AB  - OBJECTIVE: To analyses the causes and prevention of systemic complications of
      functional endoscopic sinus surgery (FESS) in patients with chronic
      rhinosinusitis. METHOD: Three typical cases were reported including their medical
      history, preoperative diagnosis, medications during preoperational period,
      complications and treatment. The causes and preventive measures of systemic
      complications were analyzed. RESULT: Three patients were all suffered from
      chronic rhinosinusitis with nasal polyps (CRSwNP). After FESS, 1 case was
      complicated with coma and hyponatremia, 1 case with acute myocardial infarction,
      and 1 case with lower extremity deep venous thrombosis. The patient with coma and
      hyponatremia was soon waked after intravenous infusion of 10% sodium chloride.
      Two patients with acute myocardial infarction and lower extremity deep venous
      thrombosis were soon completely rehabilitated after emergency thrombolytic
      therapy and endovascular intervention. Three patients were completed recovered
      from their systemic complications without any severe sequela. CONCLUSION:
      Systemic hemostatic drugs should be banned in patients with hypercoagulable state
      in perioperation period of FESS in order to avoid severe systemic complications.
      Timely vascular interventional treatment can prevent severe sequels.

PMID- 25764756
TI  - [Three-dimensional reconstruction and visualization of the fronto-ethmoidal cells
      based on CT images].
AB  - OBJECTIVE: Based on contiguous axial computed tomography (CT) images of the
      frontal sinus, a three-dimensional (3D) visualization and reconstruction of
      fronto-ethmoidal cells was performed using Intage Realia (version 2011) software
      to generate a model to accurately understand the anatomical structure of fronto
      ethmoidal cells. METHOD: Retrospective analyses of nose CT scan data of 50
      patients without sinusitis were performed. Using Digital Imaging and
      Communications in Medicine (DICOM) images of sinus axial CT scans, the 3D
      visualization and reconstruction of the sinus was performed using the Achilles
      tendon and nasal passage modes in Intage Realia (version 2011) software on
      personal computers. Two segmentations were performed on the reconstructed sinus,
      and the structures of the agger nasi, frontal cells, and supraorbital cells and
      the relative locations of the frontal sinus drainage pathway and cells were
      observed. RESULT: The 3D visualization of the fronto-ethmoidal cells and frontal
      sinus drainage pathway was successful, allowing accurate observation of the
      anatomical characteristics of the fronto-ethmoidal cells. CONCLUSION: The 3D
      visualization of fronto-ethmoidal cells can be reconstructed based on contiguous
      axial CT images of the sinus, allowing an accurate understanding of the
      anatomical structure of fronto-ethmoidal cells and is well prepared for frontal
      sinus surgeries.

PMID- 25764757
TI  - [Analysis of nasal clinical manifestations and treatment of granulomatosis with
      polyangiitis].
AB  - OBJECTIVE: To raise awareness of granulomatosis with polyangiitis by summarizing
      its nasal mani- festations and treatment experience. METHOD: Retrospective
      studies were done to the nasal clinical manifestations and treatment processes of
      21 GPA patients in this study. All were treated by the combined treatment of
      glucocorticoid, cyclophosphamide as well as tripterygium wilfordii, and 4 of them
      who had much heavier nasal symptoms were treated by endoscopic sinus operation at
      the same time. RESULT: Eighteen cases were effective treated by medical
      treatments besides 3 were died of all 21 cases. The nasal symptoms of those 4
      patients were obviously improved, and still had effective drainage of sinus after
      operation with 8-22 months follow up, although the sinus ostiums were reduced
      comparing to themselves intraoperation at different degree. CONCLUSION: GPA is
      always been ignored which will lead to delay treatment due to the lack of
      specificity of its clinical manifestations. So, enough attention is the key point
      of avoiding misdiagnosis as well as providing timely treatment for these
      patients.

PMID- 25764758
TI  - [FGFR1 selective inhibitor PD173074 can reduce proliferation and induce apoptosis
      of nasopharyngeal carcinoma].
AB  - OBJECTIVE: To study the influence of PD173074 on proliferation and apoptosis of
      nasopharyngeal carcinoma. METHOD: With immunoblotting and RT-PCR, FGFR1
      expression was detected in CNE, PONE1 and C666-1 cell lines. With MTT assay,the
      time-effect and dose-effect correlation between PD173074 and inhibition of CNE
      proliferation was evaluated. After PD173074 stimulation, the phosphorylation
      level of FGFR1 and AKT was detected with immunoblotting assay. Furthermore,
      influence of PD173074 on the activation of Caspase3 and Caspase9 was detected to
      study the underlying mechanism of why PD173074 could inhibit CNE proliferation.
      RESULT: FGFR1 has the highest expression in CNE cell line. Under incubation of 10
      nmol/L PD173074 stimulation for 36 hours to 72 hours, the phosphorylation of
      FGFR1 and AKT was impaired significantly, which further reduced the proliferation
      of CNE. Moreover, PD173074 can activate the intrinsic apoptotic pathway by
      stimulating Caspase9,which activated Caspase3 and induced the apoptosis.
      CONCLUSION: PD173074 could inhibit proliferation of nasopharyngeal carcinoma cell
      through reducing the phosphorylation of FGFR1 and AKT. Additionally, PD173074 can
      induce CNE apoptosis by activating intrinsic apoptotic pathway via cleaving
      Caspase9 and Caspase3.

PMID- 25764759
TI  - [Expression and significance of Notch receptors in the mouse model of allergic
      rhinitis].
AB  - OBJECTIVE: To investigate the expression and significance of related receptors of
      Notch signaling pathway in mouse model of allergic rhinitis (AR). METHOD: Sixteen
      BALB/c mice of seven-eight weeks old were randomly assigned to two
      groups,including controls group and model group. AR model mice was sensitized
      with ovalbumin(OVA). Symptom score, hematoxylin-eosin for pathological alteration
      and infiltration of inflammatory cells in nasal mucosa were analyzed as well as
      enzyme linked immunosorbent assay was taken to detect IgE in pe- ripheral serum.
      Nasal septum mucosa and peripheral blood mononuclear cells were collected from 16
      BALB/c mouse(8 Allegic rhinitis,8 controls). Notch 1-4 were checked by real-time
      quantitative polymerase chain reaction and flow cytometry from different levels.
      RESULT: BALB/c mice model of allergic rhinitis was established successfully. The
      mRNA of Notch1, Notch3, Notch4 in nasal septum mucosa of allergic rhinitis mice
      model groups were obviously higher than that in normal controls, and the
      difference were statistically significant (P < 0.01). However, The expression of
      Notch2 is lower than the control group and the difference was statistically
      significant (P < 0.05). In line with the above, the protein expression of Notch1,
      Notch3, Notch4 in peripheral blood mononuclear cells (PBMC) of model groups were
      significantly higher than that in health controls, and the difference were
      statistically significant (P < 0.01). But comparing control, expression of Notch2
      was lower and the difference was statistically significant (P < 0.05).
      CONCLUSION: There were significant changes of Notch genes in mouse model of AR.
      This intimated that related genes of Notch signaling pathway may paly important
      roles in the development and progression of AR and provide ideas for in depth
      study of the pathogenesis of AR.

PMID- 25764760
TI  - [The effect of 18beta-glycyrrhetinic acid on tight junctions of the nasal mucosa
      epithelial cells in rat models with allergic rhinitis].
AB  - OBJECTIVE: To observe 18beta-glycyrrhetinic acid (GA) impact on ultrastructure of
      tight junctions (TJs) of nasal mucosa epithelial cells in rats models of allergic
      rhinitis (AR). METHOD: Ninety-six Wistar rats were randomly divided into control
      group, model group, loratadine group, and 18beta-glycyrrhetinic acid group, and
      each group had 24 rats. Ovalbumin was used to establish a rat AR model. The
      behavioral changes and the tight junctions of nasal epithelial were observed and
      compared in different groups after 2,4,6 and 10 weeks intervention. RESULT: The
      length of TJs in allergic rhinitis model became shorter, electron-high-density
      plasma membrane became thicker, number of the integration loci reduced and gap of
      TJs widened or even ruptured. With the consistent effect of allergens,the changes
      of TJs in the model group aggravated gradually,and the changes of ultrastructure
      of TJs in 18beta-glycyrrhetinic acid group was relieved apparently compared to
      model group and even were close to the control model with time. CONCLUSION:
      18beta-glycyrrhetinic acid can recover the ultrastructure of the tight junctions
      of AR rat nasal epithelial cells.

PMID- 25764761
TI  - [Clinical analysis of 12 cases of nasal surgery in patients with coronary heart
      disease after accepted PCI].
AB  - OBJECTIVE: To investigate the perioperative treatments of endoscopic sinus
      surgery for nasal diseases in patients with coronary heart disease after PCI.
      METHOD: Clinical data of 12 cases of endoscopie-assised surgery such as nasal
      tumors resection,functional sinus surgery,correction of deviated nasal septum,low
      temperature plasma hemostasis in patients with coronary heart disease after PCI
      were analyzed retrospectively. RESULT: Serious bleeding did not take place with
      the 12 cases during surgery, and surgery progressed smoothly; one of patients had
      heavy nosebleed after surgery, however her condition was stable when received
      active treatment. Follow-up 3 months to 2 years, nasal diseases of 12 patients
      recovered well and symptoms were relieved; cardiovascular events such as
      hemorrhage, thrombosis and so on did not occur. CONCLUSION: Due to physiological
      function of the heart dysfunction in patients with coronary heart disease after
      PCI,they often accompany a number of trouble issues such as medical disorders,
      oral antiplatelet drugs, surgery affordability loss and increase surgical risk.
      Correct and effective perioperative treatments, strictly surgical indications are
      really necessary which can keep patients safe through perioperative period.

PMID- 25764762
TI  - [The expression of interleukin-25 in blood and nasal tissue of patients with
      chronic rhinosinusitis with nasal polyps].
AB  - OBJECTIVE: To explore the expression of interleukin-25 (IL-25) in chronic
      rhinosinusitis with nasal polyps (CRSwNP) and its potential significance in
      pathogenesis. METHOD: IL-25 expression in blood was detected by enzyme-linked
      immunosorbent assay (ELISA). IL-25 expression in tissue was detected by
      immunohistochemistry (LSAB method) from polyps (68 CRSwNP patients) and 55
      inferior turbinate mucosa from patients with deviation of nasal septum served as
      control. Complete blood count and HE staining of blood and tissue eosinophil
      infiltration degree. RESULT: IL-25 expression in CRSwNP group were significantly
      higher than the control group, the difference was statistically significant (P <
      0.01). IL-25 expression in local organizations was positively correlated with the
      number of eosinophil infiltration in CRSwNP group (r = 0.679, P < 0.01).
      CONCLUSION: The expression of IL-25 in CRSwNP patients mutually reinforcing and
      might increase eosinophil infiltration and play an important role in the
      development of CRSwNP.

PMID- 25764763
TI  - [Expression of PPAR-gamma in patients with chronic rhinosinusitis without or with
      nasal polyps].
AB  - OBJECTIVE: To investigate the expression of peroxisome proliferator-activated
      receptor gamma (PPAR-gamma) in the sinus mucosa of chronic rhinosinusitis without
      nasal polyps (CRSsNP) and chronic rhinosinusitis with nasal polyps (CRSwNP).
      METHOD: Using immunohistochemistry and RT-PCR, testing the content of PPAR-gamma
      in sinus mucosa and nasal polyps of patients with chronic sinusitis without nasal
      polyps and normal inferior turbinate, and analyzing the differences. RESULT: The
      PPAR-gamma was found both in sinus mucosa of CRSsNP, nasal polyps of CRSwNP and
      in normal inferior turbinate; (2) The expression of PPAR-gamma in sinus mucosa of
      CRSsNP and nasal polyps of CRSwNP was lower than that in normal inferior
      turbinate tissue, and the differences was prominent in statistics; (3) No
      differences in the expression of PPAR-gamma were obtained in sinus mucosa of
      CRSsNP and nasal polyps of CRSwNP. CONCLUSION: The PPAR-gamma expressed in human
      nasal mucosa, meanwhile it was descending in sinus mucosa of CRSsNP and nasal
      polyps of CRSwNP. The long-term inflammations resulted from CRSsNP and nasal
      polyps of CRSwNP might relate to PPAR-gamma, it suggested that PPAR-gamma
      agonists may offer a new therapy for the treatment of Chronic Rhinosinusitis.

PMID- 25764764
TI  - [Pedicle flap of nasal septum-basis nasi and temporal muscucofascial flap to
      repair nasoseptal perforation].
AB  - OBJECTIVE: To explore curative effect with pedicle flap of nasal septum-basis
      nasi and temporal muscucofascial flap to repair nasal septal perforation. METHOD:
      Dissecting mucoperichondrium and mucoperioseptum around the perforation and
      taking dowm and out xia-ward to the floor of nasal cavity to make a inferior
      extremity pedicle flap. Then,the flap was tumbled and sutured onto raw surface of
      contralateral side through perforation. Reapplicating autoallergic temporal
      musculofascial flap to repair another side perforation. RESULT: Repairing
      perforation Sin twelve cases were sucessfully healed in endoscope. CONCLUSION:
      The pedicle flap of nasal septum-basis nasi and temporal muscucofascial flap is
      easy to acquire and no rejection. The flap has good blood supplying, high
      survival rate and provides adequate transplantating materail to repair
      comparatively large perforation.

PMID- 25764765
TI  - [The improved nasal endoscopic dacryocystorhinostomy].

PMID- 25764766
TI  - [Application of nasal endoscope in diagnosis, etiology and treatment of
      epistaxis].

PMID- 25764767
TI  - [A clinical analysis of 132 cases with intractable epistaxis managed by nasal
      endoscopic surgery].

PMID- 25764768
TI  - [Application of simple tracheostomy in the preservation of laryngeal function in
      laryngeal cancer operation].

PMID- 25764769
TI  - [A case of the nasal septum pyogenic granuloma and literature].
AB  - A 56-year-old male had presented with left nasal bleeding repeatedly for 4 days.
      The pathological examination after resection showed pyogenic granuloma. Its
      etiology and pathogenesis, clinical features, pathological features and
      treatments were reviewed.

PMID- 25764770
TI  - [Low-temperature radiofrequency technology treatment of spontaneous tonsillar
      hemorrhage: a case report].
AB  - Patient, 30-year-old, male,was admitted to our hospital because of
      discontinuously spit fresh blood without any inducing factors for three days. In
      the course, the patient suffered mild dry sensation of pharyngeal, poor spirit
      condition, fatigue, poor sleep, poor appetite and was with black stool 2 times.
      Physical examination: T36. 6 degrees C, R 21/min, P98/min, BP135/90 mmHg (1 mmHg
      = 0.133 kPa). Bilateral tonsils were III hypertrophy and with scar shape
      surfaces. The left tonsil's surface had longitudinal small blood vessels markedly
      dilated. His oropharynx, laryngopharynx and laryngeal did not be find any obvious
      bleeding sites. Laboratory findings: WBC 13.82 x 10(9)/L, N 0.8084, L 0.1632, Hb
      81.00 g/L, HCT 25.20; PT 9.60 s, APTT 25.50 s, TT 15.80 s, FIB 1.900 g/L. After 3
      hours of admission,the patient spit out fresh blood again,checked the body to
      see:the left peri-tonsil with fresh blood and found a slowly bleeding site at the
      1/3 junction of the middle lower part of left tonsil's rear surface, the size was
      about 0.5 cm x 0.6 cm. We finally diagnosed spontaneous tonsillar hemorrhage and
      successfully managed with low-temperature radiofrequency technology.

PMID- 25764771
TI  - [Transnasal endoscopic removal of lacrimal sac and intraorbital foreign body].
AB  - We reported a case of a work-related accident involving periorbital and
      intraorbital metal foreign bodies. The patient was a 43-year-old woman whose
      nasal dorsum was struck while she was sawing wood with nails. X-ray plain films
      of skull bone and computed tomographic scan of nasal sinus revealed two 5-mm-long
      metal objects lodged in right lacrimal sac and medial bulbar space of the right
      orbit. No deficits were noted in her visual acuities, visual fields, and ocular
      movements. Based on accurate positioning by imaging examination, transnasal
      endoscopic removal of metal foreign bodies was successfully accomplished. The
      patient recovered well without any complications after surgery.

PMID- 25764772
TI  - [By nasal cavity approach resection of bigger pleomorphic adenoma in left skull
      base with nasal endoscope].
AB  - A 46-year-old female patient presented to our hospital with history of pharyngeal
      discomfort for 6 months. Physical examination showed that she had facial
      asymmetry, loss of the left nasolabial fold, rightward de- viation of uvula,
      swelling of the left soft palate. Magnetic resonance imaging revealed a bigger
      neoplasm in left pa- rapharyngeal space which invaded into left lateral skull
      base. The left internal carotid artery, vein and the styloid process was jostled
      backward. The primary clinical diagnosis is pleomorphic adenoma of the
      parapharyngeal space.

PMID- 25764773
TI  - [One case of pleomorphic adenoma originates from inferior nasal turbinate].
AB  - Pleomorphic adenoma (PA) is the most common benign tumor of the salivary glands.
      Originating from the nasal cavity is very rare. This paper reports one case of
      pleomorphic adenoma of the inferior nasal turbinate to analyze the clinic
      characteristic of this disease. Although these tumors are rarely seen in everyday
      practice, one should consider this possibility as an uncommon aetiology when
      confronted with an intranasal mass.

PMID- 25764774
TI  - [Etiologies, treatment and prognosis of olfactory dysfunction].
AB  - Olfaction is one of the ancient sensing capabilities and plays an important role
      in monitoring environment. Although olfactory loss is common, it's obviously
      underappretiated by medical community generally. In order to help patients with
      those problems, the author gives an brief review about the characters of common
      etiologies, treatment and prognosis of Olfactory Dysfunction. It's concluded that
      most usual causes resulting in dysos- mia are upper-respiratory-tract infections,
      trauma, and chronic rhinosinusitis; and our understanding of the olfaction
      mechanism grows, but frustratingly, aside from the possible therapeutic potential
      of systemic steroids, no method has been proved to have solid evidence for curing
      olfactory loss; so we need more new basic and clinic research to develop
      effective therapeutic intervention.

PMID- 25764775
TI  - [Study on the function and mechanism of Th17/Treg imbalance on mucosal remodeling
      of ECRSwNP].
AB  - Chronic rhinosinusitis (CRS) can be controlled by a combination of conservative
      treatment and surgical procedures. However, there is one group of CRS endotypes,
      refractory CRS, such as eosinophilic chronic rhinosinusitis with nasal polyp
      (ECRSwNP), for which the current treatment strategies of anti-inflammatory and/or
      antibiotic therapy or surgical removal of the lesion to improve sinus drainage
      are less effective. This lack of treatment efficacy highlights the need for
      further fundamental and clinical research to improve or restore nasal mucosal
      function of CRS. The role of the immune response in the pathogenesis of mucosal
      remodeling, which is a key problem in refractory CRS, is of particular current
      interest. ECRSwNP characterized by Th17/Treg imbalance in- duced by IL-6 has a
      different mucosal remodeling pattern. This review intends to illustrate the role
      of the imbalance between Th17 (T helper 17) and Treg (regulatory T) cells in the
      mucosal remodeling of ECRSwNP and to suggest a novel therapeutic target on
      treating ECRSwNP.

PMID- 25764776
TI  - May smoking be considered as the most important factor that determines premature
      death after hospitalization due to COPD exacerbation? Preliminary data.
AB  - INTRODUCTION: COPD, cardiovascular diseases and cancer are smoking-related
      diseases that have been accepted as the leading causes of premature mortality
      worldwide. Nevertheless, smoking is still considered to be a risk rather than a
      prognostic factor for mortality. The aim of the study was to determine the most
      important factors in predicting the risk of premature death after effective
      hospital treatment of COPD exacerbation. MATERIAL AND METHODS: 34 consecutive
      patients hospitalized with COPD exacerbation were followed up and their post
      hospitalization survival time was analyzed. Basic clinical data (BORG, MRC, BMI,
      pack-years and age) was collected. The following tests that were performed prior
      to discharge were assessed: 6MWT, spirometry, body plethysmography, diffusion
      capacity, transthoracic echocardiography (TEE) and whole night polysomnography.
      Routine laboratory and immunoenzymatic tests (hs-CRP, endothelin 1 (ET-1), NT
      proBNP, IL-6, TNF-alfa) were analyzed. RESULTS: The average follow-up period was
      15.1 +/- 8.2 month. The mortality rate was 3/34 = 8.8%. Univariable analysis
      revealed significant differences that indicated a greater number of deaths at
      higher values of: pack-years (p = 0.02), BODE (p = 0.03), heart rate (HR) after
      6MWT (p = 0.003), ET-1 (p = 0.04), but at lower values of TLCO/VA (p = 0.03) and
      6MWT-distance (p = 0.006). Multivariable analysis revealed that only pack-years
      (p = 0.005) were predictive for mortality. CONCLUSIONS: Smoking history seems to
      have the strongest impact on short-term mortality after recovery from COPD
      exacerbation.

PMID- 25764777
TI  - [Influence of toxin botulin on walk stereotype of children with juvenile cerebral
      palsy. The functional examination performed by BTS, comprehensive movement
      analysis system. A preliminary report].
AB  - INTRODUCTION: Juvenile Cerebral Palsy--is caused by damage of the motor control
      centers of the developing brain (cerebral refers to the cerebrum, which is the
      affected area of the brain, although the disorder probably involves connections
      between the cortex and other parts of the brain and palsy refers to disorder of
      movement). The clinical symptoms of juvenile cerebral palsy are very diversified
      and include gross and fine motor-coordination disorders, manual ability,
      locomotion, perception and response, speech, psychomotor retardation, emotional
      disorders. The primary therapeutic problem in children with cerebral palsy is
      learning to move in a lower position and learning to walk. The aim of this
      research is evaluation the action of the botulinum toxin on gait pattern of
      children with cerebral palsy. Application of a comprehensive BTS analysis of gait
      will get accurate, consistent EBM (Evidence Base Medicine) results. MATERIAL AND
      METHODS: The children with pyramidal syndrome of juvenile cerebral palsy have
      been included in the examinations. The children have been divided into 2 random
      groups: group I--children treated with standard therapy a neurodevelopmental
      rehabilitation and classic kinesiotherapy, group II--hildren treated with
      standard therapy --eurodevelopmental rehabilitation, classic kinesiotherapy and a
      botulinum toxin. The children were examined three times: before the therapy,
      after 6 weeks of treatment and after 3 months of treatment. In the research BTS
      comprehensive motion analysis system have been used where influence of toxin
      botulin on walk stereotype of children was assessed. RESULTS: The treatment
      connected with standard rehabilitation and using botulinum toxin brings quicker
      walk improvement. Comparing the above treatment methods of influence on the walk
      stereotype of children with juvenile cerebral palsy, we can confirm, that
      standard treatment brings regular improvement, still, it requires longer period
      of time, often even 3 months. Using botulinum toxin brings quicker walk
      improvement, after 6 weeks only, which is a clear, but short-term result.
      CONCLUSIONS: Botulinum toxin has a positive effect on gait parameters in
      children, especially until 3 months, after this time parameters are not
      better..Concomitant treatment with standard therapy and botulinum toxin should be
      used becouse it is possitive treatment for locomotion of children with cerebral
      palsy.

PMID- 25764778
TI  - Subclinical postural instability detected by stabiloplatform examination in the
      patients with vascular mild cognitive impairment--Part 1.
AB  - INTRODUCTION: Postural instability and balance dysfunction have been identified
      in the patients with dementia. AIM: The aim of our study was to evaluate
      subclinical postural and balance features in patients with vascular mild
      cognitive impairment (VaMCI). METHODS: The study subjects were the patients with
      VaMCI (n = 62) and those without cognitive impairment (n = 35). Our cognitive
      performance examination consisted of the battery of tests including Luria memory
      words test, Shulte's tables, semantic and phonemic fluency test, the clock
      drawing test and Montreal cognitive assessment (MOCA). Postural function and
      balance control were assessed by computerized static ("Stabilan 01" Russia) and
      dynamic ("Gravistat", Belarus) stabiloplatforms using a biofeedback principle.
      RESULTS: In the static stabiloplatform examination more pronounced postural
      instability in VaMCI patients was evidenced by larger gravity center displacement
      radius (p < 0.05) and confidence ellipse area (p < 0.05). In the dynamic
      stabiloplatform examination it was manifested by the reduced number of errors as
      attempts to maintain postural stability (p < 0.0001), a decrease in the error
      rate (p < 0.0001) and increase in the average time of a postural response as time
      spent for one error (p < 0.0001). CONCLUSIONS: Subclinical postural instability
      detected by the stabiloplatform examinations may be of value in earlier VaMCI
      diagnosis.

PMID- 25764779
TI  - [Evaluation of effectiveness of local cryotherapy in patients with post-stroke
      spasticity].
AB  - INTRODUCTION: Spasticity is a source of functional limitations in patients. It
      leads to weakening of muscles, reduced mobility, muscle fatigue and irreversible
      changes in tissues. The aim of the study is to evaluate the effectiveness of
      local cryotherapy in patients with post-stroke spasticity. MATERIAL AND METHODS:
      The study was conducted in 56 patients with post-stroke spasticity. They were
      divided into two groups (Group 1 was administered cryotherapy and kinesitherapy
      and Group 2- kinesitherapy only). The researchers assessed the level of
      spasticity according to the Modified Ashworth Scale as well as functions of lower
      limbs, upper limbs and hands according to the Brunnstrom Scale twice (before and
      after the therapy). The findings were statistically analyzed. RESULTS: In the
      treatment groups decreased muscle tone. An improvement of the efficiency of
      locomotion and hand in performing activities of daily living. More favorable
      results were observed in group 1. CONCLUSIONS: Local cryotherapy combined with
      kinesitherapy appeared to be more effective in treating spasticity rather than
      kinesitherapy alone. A decrease in spasticity and an improvement of the limb
      function indicate a stabilization of muscular tension in patients with disorders
      upper motor neuron.

PMID- 25764780
TI  - [Nonalcoholic fatty liver disease in obese patients].
AB  - INTRODUCTION: Nonalcoholic fatty liver disease (NFLD) is a heavy healthy problem
      in well civilized Countries, where obese appear more frequently. Mostly disease
      has a benign process, but in some radical case might lead to cirrhosis or even to
      cancer. There is a demand on specific researches about NFLD, cause knowledge
      about pathogenesis and epidemiology is not clear. The aim of this researches is
      to rate frequency of occurring nonalcoholic fatty liver disease in obese type II
      and III patients with reference to patients with correct body weight. MATERIAL
      AND METHODS: Research group comprise 70 patients of Clinical Health Resort
      Hospital in Ciechocinek with BMI higher than 35. Control group comprise 20
      patients with BMI lower than 30. In case of all patients fatty liver qualities
      were rate by ultrasounds scaning examination. For additional diagnostic following
      parameters were rated: liver enzyme ASPAT/ALAT levels, lipids level, glycemic
      level before and after meal. RESULTS: In case of 52 patients from research group
      fatty liver qualities were noticed, it is about 65% of whole group. Much more
      often fatty liver qualities had been noticed about patients witch III degree of
      obese (94%). In control group we didn't notice fatty liver qualities in any
      patients. ALAT level was statistical relevant (p = 0.0006) higher in research
      group (32 U/l) then level in control group (20,3 U/I). ASPAT level in research
      group amounted to 28.7 U/l and in control group only 19.8 U/l. Difference between
      those two group was statistical relevant (p = 0.0005). CONCLUSION: Nonalcoholic
      fatty liver disease occur average in case of 65% obese patients but in cease of
      patients with III degree obese is about 94%. That disease ought to be treated
      like a complication of obese.

PMID- 25764781
TI  - [Radioiodine--today's trends in treatment of benign thyroid diseases].
AB  - Radioiodine therapy is a highly recognizable method of treatment of benign
      thyroid diseases. The therapy gains a widespread interest of research groups,
      which find it as a promising weapon against endocrine disorders caused by benign
      thyroid diseases. According to the latest scientific research, factors,
      previously thought to be impossible to modify (intra-individual variation in
      radiosensitivity), has become modifiable. This will allow to establish a dose,
      which will affect functioning of other organs in the smallest possible way and
      will minimize the risk of side effects. The word, radioiodine" may raise some
      concern among those who are not highly familiar with endocrinology, but in fact
      it is a safe method. It is worth to mention that, according to recent research,
      consumption of common food products can reduce or even prevent potential side
      effects of radioiodine treatment.

PMID- 25764782
TI  - [The newest perspectives on diagnostic methods and treatment of insulinoma].
AB  - Insulinoma is the most common hormonally active neuroendocrine tumor of the
      pancreas. Low blood sugar, caused by excessive secretion of insulin from the
      tumor cells, leads to a variety of symptoms (e.g. signs of neuroglycopaenia),
      that may be mistaken for diseases of the central nervous system, psychiatric
      disturbances or cardiovascular conditions. That is why a lot of attention should
      be brought to the diagnostic tests towards insulinoma. The development of imaging
      techniques in the past years has lead to the possibility of locating an
      insulinoma of a few milimetres in size, which is helpful to avoid the need of a
      blind resection and preserves the pancreatic parenchyma. 90% of insulinomas are
      benign and surgery is the treatment of choice. However, as in any neuroendocrine
      tumor, a malignant form may occur--resection of the metastases is the only
      curative method, but radiofrequency ablation, selective internal radiation
      therapy, hepatic artery embolization or chemoembolization, can also have positive
      therapeutic applications. Systemic therapies regarding malignant insulinoma are:
      chemotherapy, somatostatin analogs, radiolabelled somatostatin analogs and the
      newly developed biological targeted therapies such as everolimus--oral inhibitor
      of the mammalian target of rapamycin, and sunitinib--the tyrosine kinase
      inhibitor.

PMID- 25764783
TI  - [Oral health in multiple sclerosis patients].
AB  - Multiple sclerosis (MS) is a chronic demyelinating disease of the central nervous
      system occuring in young adults, mainly female. MS dominates in Caucasians living
      in regions far away from the equator. The coexistence of genetic and
      environmental factors is considered in its etiopathogenesis. MS mostly occurs in
      the form of relapses and remissions, leading to the physical disability and
      cognitive decline. The diagnosis is based on MRI images and cerebrospinal fluid
      testing. The current guidelines for therapy recommend immunosuppression (steroids
      during relapses) and immunomodulation. Symptomatic treatment of pain or muscle
      rigidity is used additionally. The epidemiological data draw attention to the
      geographical distribution of indicators related to the increased prevalence of MS
      and dental caries. The role of D3 vitamin is discussed in the development of both
      diseases, but the role of amalgam filling in the development of MS is rejected.
      The demyelinating process in MS and applied treatment predispose to the
      neurological pain in the facial area or the temporomandibular joints. The
      increasing disability and used treatment enhance the susceptibility to mucosal
      inflammation and xerostomia, and activate viral and fungal infections. Patients
      with MS require regular dental control often in conditions arranged for disable
      people.

PMID- 25764784
TI  - [Headaches and multiple sclerosis].
AB  - The article discusses the possible association between multiple sclerosis (MS)
      and headache. MS has a broad range of neurological symptoms, but headache is not
      included among them. Research on the link between MS and headache focuses on
      primary headaches such as migraine, tension-type headache and cluster headache.
      Studies on the possible association between MS and migraine have had conflicting
      results and have found a wide range of prevalence rates for migraine in MS
      patients. The possible mechanisms proposed linking migraine and MS can be
      unidirectional, bidirectional or involving a common cause. The prevalence of TTH
      in MS patients is similar to that observed in the general population.
      Immunotherapy may play a role in inducing headache.

PMID- 25764785
TI  - [Hyperprolactinemia unrelated to prolactinoma].
AB  - Hyperprolactinemia, defined as prolactin levels above the upper limit of normal
      range, is the most frequent hypothalamus-pituitary dysfunction. Clinical symptoms
      of hyperprolactinemia in women include oligomenorrhea, infertility, and
      galactorrhea, while in men the condition may lead to hypogonadism, decreased
      libido, erectile dysfunction, infertility, gynecomastia, and, in rare instances,
      galactorrhea. In many patients, hyperprolactinemia results from the presence of
      prolactinoma, which is considered as the most common hormone-secreting pituitary
      tumors. However, transient or long-term hyperprolactinemia may also develop
      during different physiological situations or due to several diseases. It is also
      a frequent but often neglected side effect of many drugs, particularly of
      antipsychotics. Finally, hyperprolactinemia may be secondary to the predominance
      of high molecular mass circulating prolactin forms that have been postulated to
      represent complexes of prolactin and anti-prolactin immunoglobulins
      (macroprolactinemia). The cause of hyperprolactinemia determines its treatment.
      In this paper, we review the causes of hyperprolactinemia unrelated to
      prolactinoma, providing a differential diagnosis of this condition.

PMID- 25764786
TI  - [Physiotherapy potentials improve the calf muscle pump function in chronic venous
      insufficiency].
AB  - Mechanism of the calf muscle pump plays a major role in venous blood return from
      peripheral parts of blood vessels of lower extremities. It enables a smooth
      venous blood movement from the deep venous system segment located below in a
      direction to the segment lying above which effectively prevents a distal blood
      stasis and veno-lymphatic edema of lower limbs. Calf muscle pump dysfunction
      together with disorders in the construction of blood vessels walls and with
      endurance weakness of valves, leads to venous hypertension and contributes to the
      development of venous insufficiency. The aim of this paper is to demonstrate the
      theoretical basis including venous return physiology and the mechanism of lower
      limbs venous--muscle pump as well as provide practical application of
      physiotherapy methods to support the properfunction of presented calf muscle
      pump. Examples in the field of physical medicine, compression therapy and
      kinesiotherapy for improving the efficiency of lower extremity muscles, providing
      a physiological venous return.

PMID- 25764787
TI  - [Effect water intake on body weight].
AB  - Water is essential for life. There wouldn't be the proper functioning of body
      processes without it. An inadequate water intake relative to recommendation
      contributes to the decline in physical capacity and adversely effects on
      cognitive function and mood. On the other hand, an adequate water intake helps
      maintain the balance between total energy intake and daily energy expenditure and
      determines the correct rate of fat oxidation. This might be useful and commonly
      used in weight reduction and thus might favorably affect on body composition in
      overweight and obese people by increasing the total body water and lean muscle
      mass and might contribute to a decrease in body fat. Research results indicate
      clearly that drinking water instead of caloric beverages might be an effective
      way to reduce daily total energy consumption and in this way might may contribute
      to the reduction of weight, body circumferences and body fat.

PMID- 25764788
TI  - [Expert's opinion on recommendations for water and other beverages consumption in
      elderly?].
AB  - The article encloses definition of water role and its body requirement, review of
      water balance and management in older persons regarding characteristic of this
      age group and concomitant disorders. Based on current literature and expert's
      opinion the recommendations for water consumption were expressed with estimation
      of insufficient apply and oversupply, evaluation of hydration state, domestic
      water sources in diet with accent on influence of proper hydration on comfort and
      good health.

PMID- 25764789
TI  - [Exercise and aging: regulation of mitochondrial function and redox system].
AB  - Evidence shows that aging is closely related to mitochondrial decay and redox
      imbalance. With aging, both mitochondrial content and protein synthesis declined
      and free radicals, the by-products of mitochondrial metabolism and their
      oxidation to lipids, proteins and nuclear acids increased. The age-related
      declines in mitochondrial function and redox imbalance affect physical function,
      induce insulin resistance and neurodegenerative diseases, such as Alzheimer's and
      Parkinson's disease, thus, play a major role in regulation of life span.
      Therefore, mitochondrion may be the most important determinant of life span.
      Increasing evidence demonstrates that long-term aerobic exercise could prevent
      age-related diseases and improve life quality of aged people. Exercise may
      possibly stimulate mitochondrial biogenesis and phase II antioxidant defense
      system to regulate mitochondrial function and balance of redox system. Therefore,
      regular aerobic exercise may prevent age-related diseases, increase life quality
      and prolong life span through regulation of mitochondrial function and redox
      balance.

PMID- 25764790
TI  - [Mitochondrial quality control: the target for exercise to promote health and
      prevent disease].
AB  - Regular exercise has been known to have many benefits, for example, improving
      physical performance, promoting health and preventing chronic diseases such as
      metabolic diseases. As a very important organelles in eukaryotic cells,
      mitochondria exhibit superb plasticity in response to exercise. Exercise may
      promote mitochondrial biogenesis and eliminate the dysfunctional mitochondria via
      mitophagy in order to maintain the normal function of the mitochondrial network.
      These dynamic changes keep mitochondria in health state and ensure the energy
      supply for cells. This review summarized the studies on the regulation of
      mitochondrial quality control by exercise, and provided a reasonable explanation
      for exercise to promote health and prevent diseases.

PMID- 25764791
TI  - [The benefits of exercise and diet on cognitive function in the elderly with an
      emphasis on the uunderlying epigenetic mechanisms].
AB  - The Chinese society is rapidly aging. As a result, curbing the aging process and
      preventing cognitive decline associated with aging are increasingly important.
      Life-style change is a method that could achieve such a goal with relatively good
      reproducibility and low cost. The current study summarizes the benefits of sports
      and dietary intervention on cognitive function in the elderly, with an emphasis
      on the underlying epigenetic mechanisms. For future studies, improvement in the
      following aspects is needed: more rigorous study design and inclusion of multiple
      factors and their interaction.

PMID- 25764792
TI  - [Physical exercise and mental health: cognition, anxiety, depression and self
      concept].
AB  - This review focuses on the benefits of regular physical activity participation
      have mainly focused on cognitive functioning, anxiety and depression, and self
      concept. It is well documented that ex- ercise can enhance cognitive functioning,
      improve executive function at old age, and improve mental abil- ity of children
      labeled as educational subnormal or disability. Regular exercise has been used to
      reduce stress and ward off anxiety and feelings of depression. In addition,
      exercise can improve self-esteem and positive outlook in life. Studies in these
      three main areas were reviewed and issues and future directions were highlighted.

PMID- 25764793
TI  - [Research advance on angiogenesis in ischemic heart induced by aerobic exercise
      and stem cell mobilization].
AB  - Aerobic exercise has specific angiogenesis effect, also in the ischemic heart.
      But its mechanism has not been fully clarified. Coronary microvascular
      angiogenesis is the precondition of heart repair after myocardial infarction
      (MI). Recent studies have shown that angiogenesis is caused by endogenous stem
      cell/progenitor mobilization and participation, and its paracrine effects on
      endothelial cells (EC) function and microvascular distribution. Exercise could
      mobilize and activate the expression and secretion of endogenous stem cell and
      angiogenic factors, and affect the cardiac angiogenesis in epigenetics.
      Investigating the effect of different exercise methods and intension on ischemic
      cardiac angiogenesis and its molecular mechanism are of great significance on
      prevention and postoperative rehabilitation of MI. This review summarized the
      main mechanism, existing problems and related research progress on exercise
      improving ischemic cardiac angiogenesis through cardiac angiogenesis and its
      regulation mechanisms, endogenous stem cell mobilization and participates in
      angiogenesis of ischemic heart, and exercise improving ischemic cardiac
      angiogenesis through stem cell mobilization.

PMID- 25764794
TI  - [The cellular mechanisms of exercise adaptation from the perspective of skeletal
      muscle plasticity].
AB  - As highly plastic tissue, skeletal muscle adapts to stressors such as exercise.
      Reasonable amount of exercise is known to play a role in the prevention of
      cardiovascular diseases, diabetes and cancer. However, in the field of Exercise
      Physiology, the debate has been on for a while as to which kind of exercise is
      more effective in health promotion. In this review, the authors contrast and
      compare the signaling pathways mediated by different types of exercise, and
      boldly speculate the intrinsic similarities and discrepancies among them, hoping
      to enrich the theoretical frames of exercise adaptation, as well as provide
      effective exercise regimen to the public.

PMID- 25764795
TI  - [Environment of high temperature or air particle matter pollution, and health
      promotion of exercise].
AB  - It is important to keep human health in special environment, since the special
      environment has different effects on health. In this review, we focused on high
      temperature and air particle matter environment, and health promotion of
      exercise. Exercise and high temperature are the main non-pharmacological
      therapeutic interventions of insulin resistance (IR). PGC-1alpha is key
      regulatory factor in health promotion of exercise and high temperature. The novel
      hormone Irisin might be the important pathway through which heat and exercise
      could have positive function on IR. Air particle matter (PM) is associated with
      onset of many respiratory diseases and negative effects of exerciser performance.
      However, regular exercise plays an important role in improving health of
      respiratory system and lowering the risk induced by PM. Furthermore, free
      radicals and inflammatory pathways are included in the possible mechanisms of
      positive physiological effects induced by exercise in air particle matter
      environment.

PMID- 25764796
TI  - [Advances in mechanisms of health benefits of exercise and nutrition].
AB  - Adequate physical activity/exercise and nutrition are the footstone for health,
      and primary components of healthy life style and prevention and treatment of life
      style-related diseases. Here we briefly review the recent advances in mechanisms
      of health benefits of regular physical activity/exercise and adequate nutrition,
      mitochondrial nutrients, and so on.

PMID- 25764797
TI  - [The Detections, functions and regulations of G-quadruplex].
AB  - G-quadruplex structure was found recently as a special secondary structure of
      Nucleic acid. It can be formed easily and widely in vivo and has important
      biological functions. Researchers have detected the formation of G-quadruplex in
      vitro and solved its crystal structure by using specific fluorescent probes,
      antibodies, etc., which are constantly discovered or synthesized. G-quadruplex
      structures are distributed widely not only in the significantly functional region
      as telomere, promoter, gene extron, but also in the 5 'untranslated region
      (5'UTR), intron and 3'flanking region (3'UTR) of RNA. They play vital roles in
      the extension of telomeres, DNA replication, transcription, meiosis,
      recombination, and otherpivotal life processes. Additionally, they can exert anti
      tumor, anti-virus, inhibiting angiogenesis and other important functions.
      Currently anticancer drugs based on G-quadruplex structure have entered clinical
      trials and obtained good curative effects. G-quadruplex can be regulated
      endogenously by the methylation and the interaction with many proteins and stays
      in a balanced content and morphology. Some exogenous small molecules can also
      play such regulatory roles. This paper will systematically summarize detection
      methods, special functions and regulation of G-quadruplex in the fields of
      chemistry, biology and medicine.

PMID- 25764798
TI  - [Exosome in cancer diagnosis and treatment].
AB  - Exosomes secreted by various types of living cells are small vesicular bodies
      that contain many types of proteins and RNAs. Such membrane-coated nano-scale
      structures are extensively involved in the processes of intercellular material
      exchange and signal communication, thus to conduct important functions under
      physiological and pathological conditions. Exosomes exist in high abundance in a
      wide range of body fluids, including peripheral blood, urine, ascites, and
      amniotic fluid, etc. The exosome from different tissues poses substantial
      difference in molecular components and biological functions which are dynamically
      influenced by extracellular matrix and microenvironment. Tumor-derived or tumor
      associated exosomes can be an important regulatory mechanism during cancer
      development and progression. The detection and analyses of tumor-derived exosomes
      can provide potential reference for cancer early diagnosis, treatment assessment
      and prognosis. Besides, exosomes and their modified variants can be directly used
      as vectors for cancer intervention of gene or drug delivery. Exosome-related
      studies have brought up a booming research field of cancer biology, which
      following the principle of translational medical research, will shed light on the
      research of tumor biology and significantly accelerate the developments of novel
      cancer diagnosis methods, as well as novel strategies for cancer therapy.

PMID- 25764799
TI  - [Cell lineage tracing].
AB  - Cell lineage tracing is to track certain cell and all of its progeny. From the
      20th century, lineage tracing has provided a predominant method to study organ
      development, tissue repairiaed cell fate-determination. Recently, the rapid
      development of technique for gene engineering, especially the application of
      Cre/loxp recombinase system expands the application range of lineage tracing.
      Here we discuss the application of lineage tracing technique in different
      studies, and summarize the characteristics and recent progresses of this
      technique.

PMID- 25764800
TI  - [The effects of microgravity on blood vessels and vascular endothelial cells].
AB  - The dysfunction of vascular system is one of the main causes of orthostatic
      intolerance induced by microgravity. Vascular endothelial cell is a single layer
      on the inner wall of the blood vessel and is the important component of the blood
      vessel wall. Vascular endothelial cell plays a pivotal role in the regulation of
      vascular functions, such as serving as a permeability barrier, regulating
      vasoconstriction and vasodilatation. Recent studies have demonstrated that
      microgravity may have different effects on vascular sys- tem and vascular
      endothelial cells in different parts of the body, such as increasing
      vasoconstrictor reactivity and decreasing vasodilator reactivity of cerebral
      arteries, decreasing vasoconstrictor and vasodilator reactivity of carotid and
      abdominal aortic arteries, decreasing vasoconstrictor reactivity and increasing
      vasodilator reactivity of pulmonary arteries, decreasing vasoconstrictor
      reactivity of mesenteric arteries and veins and lower extremity arteries. In
      addition, microgravity can promote the growth of vascular endothelial cells in
      the large vessels and inhibit the growth of microvascular endothelial cells. This
      paper summarized the research progress in the effects of microgravity on blood
      vessels and vascular endothelial cells.

PMID- 25764801
TI  - [Class II histone deacetylases and glucolipide metabolism].

PMID- 25764802
TI  - [Research advances in the biology of gasotransmitters: NO, CO and H2S].

PMID- 25764803
TI  - [Progress of DNA methylation in development of central nervous system].

PMID- 25764804
TI  - [Water-borne outbreak of Yersinia enterocolitica O8 due to a small scale water
      system].
AB  - A water-borne outbreak of Yersinia enterocolitica O:8 associated with a small
      scale water system occurred during July-August 2011 in Toyama Prefecture, Japan.
      Escherichia coli was not detected in tap water from the small-scale water system.
      However, the maximum concentration of viable bacteria in the tap water was
      700CFU/mL, which exceeds the legal standard for purity of tap water (100CFU/mL).
      Furthermore, Y. enterocolitica O8 was isolated from the tap water with the use of
      immunomagnetic beads prepared with anti-Y. enterocolitica O8 antibodies. Pulsed
      field gel electrophoresis analysis identified 3 isolates from tap water and 5
      isolates from 4 patient stool specimens as belonging to the outbreak strain. An
      epidemiological investigation revealed improper management of the residual
      chlorine concentration in the tap water. This is the first report of an outbreak
      of Y. enterocolitica due to tap water from a small-scale water system in Japan.

PMID- 25764805
TI  - [Malaria cases treated with artemether/lumefantrine in Japanese travelers].
AB  - Artemisinin-based combination therapy (ACT) has been the standard treatment for
      uncomplicated malaria. Although not licensed in Japan, artemether/lumefantrine
      (AL), one type of ACT, has been administered to patients with malaria since 2002
      by the Research Group on Chemotherapy of Tropical Diseases. Herein, we reviewed
      malaria cases treated with AL in Japanese travelers. A retrospective study was
      conducted at the National Center for Global Health and Medicine from October 2005
      to March 2013. There were 19 malaria patients treated with AL, and 10 falciparum
      malaria patients treated with AL only. In these 10 patients treated with AL only,
      the median time of fever clearance was 25.0 hours (range:14-66 hours), and the
      median time of parasite clearance was 36.0 hours (range:16-62 hours). There was a
      positive correlation between parasitemia and time from the start of therapy to
      the disappearance of the parasites. Parasitemia was higher (4.05% vs. 0.24%; p =
      0.044) and parasite clearance time was longer (55.5 hours vs. 31.5 hours; p =
      0.044) in the cases of recrudescence than non-recrudescence, respectively. Three
      of the 19 malaria patients showed recrudescence of malaria after treatment with
      AL. The reason that treatment failure was more frequently observed in this study
      than in previous reports may be related to poor absorption of lumefantrine owing
      to gastrointestinal symptoms, insufficiently ingested fatty foods, or high
      parasitemia on admission. The World Health Organization recommends that
      intravenous antimalarials should be administered in cases of severe malaria
      however, this is not applicable in Japan. Further studies are needed to
      distinguish patients with malaria who are treatable with ACT from those who
      should be treated initially with other intravenous antimalarials.

PMID- 25764806
TI  - [MRSA clones identified in outpatient dermatology clinics].
AB  - To know the characteristics of methicillin-resistant Staphylococcus aureus (MRSA)
      strains disseminating through the Japanese community, we have determined types of
      Staphylococcal cassette chromosome mec (SCCmec) elements, Multi-Locus Sequence
      Typing (MLST), and carriages of four exotoxin genes (toxic-shock syndrome toxin,
      Panton-Valentine Leukocidine, and exfoliative toxins a and b) using 54 MRSA
      strains isolated from outpatients attending dermatology clinics at the four
      university hospitals of Juntendo University. Ten clonal complexes and 12 SCCmec
      types have been identified. As a result, more than 15 MRSA clones that were
      defined by the combination of genotype and SCCmec type, were identified. Among
      them, Clonal Complex (CC) 5-type IIa SCCmec strains were the most major (16
      strains). In contrast to the fact that CC5- type IIa SCCmec strains known as a
      hospital-associated MRSA clone in Japan carried toxic-shock syndrome toxin gene
      (tst), only 2 of 16 strains have been shown to carry tst. Thirty-eight (70.4%) of
      isolates belonged to the clones distinct from the CC5-type IIa SCCmec strains.
      Among them, CC8 strains were major (12 strains), which contained 9 tst-positive
      CC8-type IVl SCCmec clones and a CC8-type IVa SCCmec strain carrying the Panton
      Valentine Leukocidin gene (lukS, F-PV). Clones related to impetigo were also
      identified: 7 exfoliative toxin b (etb) -positive clones, CC89-type IIa SCCmec
      and CC89-type V SCCmec strains; and 2 exfoliative toxin a (eta) -positive CC121
      type V SCCmec strains. Other clones were as follows: CC1-type IVa SCCmec, CC8
      type I SCCmec, CC81-type IVg SCCmec, CC97-type IVc SCCmec, CC91-type IVa SCCmec,
      CC59-type IVg SCCmec, CC45-type IIn SCCmec, CC89-SCCmec nontypeable, and CC8-type
      IVm, novel subtype of type IV SCCmec were identified in this study. Our data
      showed that many novel MRSA clones have emerged in the community.

PMID- 25764807
TI  - [Invasive pneumococcal disease of serotype 6C with skin and soft tissue
      infections in an immunocompetent adult].
AB  - We report herein on a rare case of deep-soft tissue infection due to invasive
      pneumococcal disease (IPD). A 77-year-old woman was admitted to our hospital with
      progressive pain in the right upper arm and the distal leg associated with
      swelling. We diagnosed the condition as multiple instances of cellulitis that
      were initially treated with ceftriaxone and clindamycin. Penicillin-susceptible
      Streptococcus pneumoniae (PSSP) was isolated from blood cultures on admission.
      Although inflammatory marker levels improved following susceptive antibiotic
      therapy (ampicillin), multiple abscesses, septic arthritis and osteomyelitis were
      detected with image testing. The antibiotic was then changed to meropenem and
      arthroscopic surgery was performed for the right shoulder; the patient's clinical
      symptoms improved. Since pneumococcal infection including skin and soft tissue
      infection (SSTI) often causes blood stream invasion or metastatic suppurative
      complications, metastatic lesions or multiple abscesses should be taken care of.

PMID- 25764808
TI  - [A case of lung abscess due to Aspergillus viridinutans in a patient with
      aplastic anemia].
AB  - A 75-year-old woman with aplastic anemia was admitted to our university hospital
      because of a dry cough that had persisted for a month. Chest computed tomography
      showed a mass shadow with a central low attenuation area in the lower lobe of the
      left lung. Filamentous fungus resembling Aspergillus fumigatus was cultured from
      the specimens obtained by transthoracic needle aspiration biopsy and
      bronchoalveolar lavage. The initial diagnosis was a lung abscess due to A.
      fumigatus, although the patient did not respond well to antifungal agents.
      Subsequently, the filamentous fungus was identified as Aspergillus viridinutans
      by sequence analysis of the beta-tubulin gene, and the patient was successfully
      treated with combination therapy along with granulocyte colony-stimulating
      factor. The incidence of A. viridinutans infection is very rare. A. viridinutans
      is morphologically similar to A. fumigatus; however, the response to antifungal
      agents is generally worse than that observed in A. fumigatus infections.
      Therefore, the selection of agents and supplemental therapy is of vital
      importance in cases of A. viridinutans infection.

PMID- 25764809
TI  - [Two cases of emphysematous urinary tract infections successfully treated with
      conservative management].
AB  - Emphysematous urinary tract infection is a rare, fulminant complication that is
      characterized by the presence of gas in the pelvicaliceal system, renal
      parenchyma, perinephric tissues and retroperitoneum. Surgical resection is
      usually regarded as the treatment of choice, however several studies have shown
      the safety and efficacy of conservative management under the correct diagnosis
      and appropriate antibiotic administration. We herein report on two cases of
      emphysematous urinary tract infection, pyelonephritis and cystitis infected with
      ESBL-producing Eschrerichia coli, complicated with diabetic mellitus which were
      successfully treated with conservative treatment.

PMID- 25764810
TI  - [Two cases of Paragonimiasis westermani in a Chinese family diagnosed with the
      Ouchterlony double diffusion method].
AB  - We report two cases of Paragonimus westermani infection in a Chinese family in
      Japan. A 41-year-old husband and his 40-year-old wife were infected with P.
      westermani after consuming a homemade Chinese traditional "Drunken Crab." They
      were a family with two children who had lived in Japan for 19 years. The crabs
      were Eriocheir japonica sent from the Kyusyu area that they had pickled at home
      with soy sauce and Chinese liquor for 5 days. Their children did not eat any of
      the crabs. One month after consuming the crabs, the husband came to our
      outpatient clinic with fever and chest pain and his wife also presented with a
      persistent cough. Both patients had a high peripheral blood eosinophil count
      (husband:18,900/MUL, wife:10,600/MUL) with pulmonary effusion, nodular shadow,
      and pneumothorax in chest X-ray findings. Paragonimiasis was suspected from the
      episode of consuming the crabs. No parasite eggs were seen in their sputum and
      stool samples. A multiple-dot ELISA was performed with the sera to screen for
      parasitic infections, but the result was only weakly positive for P. westermani
      antigen in the husband and a slightly positive reaction in the wife. The
      diagnosis of P. westermani was achieved with the double diffusion Ouchterlony
      method using P. westermani antigen and P. miyazakii antigen. Praziquantel
      administration for three days improved the symptoms in both patients. The
      Ouchterlony method proved useful in diagnosing paragonimiasis in these cases.

PMID- 25764811
TI  - [A case-control study of patient characteristics and risk factors for hospital
      acquired Acinetobacter bacteremia in our hospital].

PMID- 25764812
TI  - [Characteristic of norovirus genotypes detected in Okazaki City between April
      2007 and March 2013].

PMID- 25764813
TI  - [Influence of synthetic peptide of active GM-CSF center on hemopoiesis recovery
      in C57Bl/6 mice after exposure to fractionated radiation].
AB  - The research allowed evaluation of the influence exerted by synthetic peptide of
      the active center of granulocyte-macrophage colony-stimulating (GM-CSF) factor on
      hematopoiesis in mice both under normal physiological conditions of the animals,
      and during the period of post-exposure recovery of hematopoiesis. It has been
      demonstrated that a synthetic peptide of the active GM-CSF center is able to
      exert a stimulating effect on animals with radiation-induced hematopoiesis
      inhibition. A single injection of the preparation at a dose of 0.005 MUg/g to
      female C57Bl/6 mice, which had been exposed to fractionated exposure at a dose of
      10 Gy and developed inhibition of bone-marrow hematopoiesis and cytopenia,
      exerted a stimulating effect on the granulocyte and monocyte lineages of
      hemopoiesis. Injections of an active GM-CSF center peptide to irradiated animals
      did not influence the content of CFUs in thebone-marrow (BM), but they exerted a
      stimulating influence on the population of these cells in unexposed animals. No
      effect of the influence of the preparation on the development of extramedullary
      hematopoiesis in the spleen was observed in the irradiated mice. The study showed
      that a peptide active site GM-CSF is a promising drug in terms of its use for the
      treatment of radiation-induced myelosuppression.

PMID- 25764814
TI  - [The study of aberrant methylation in blood leukocytes of liquidators of the
      Chernobyl accident].
AB  - The study of aberrant methylation of CpG islands in the promoter regions of genes
      (P16/CDKN2A, P14/ARF, RASSF1A, GSTP1) in blood leukocytes of liquidators of the
      Chernobyl accident (n = 83, 38-76 years of age) and control subjects of two
      groups (n = 48, age <= 35 and n = 65, age > 35) was carried out using methylation
      sensitive restriction endonuclease analysis followed by PCR. The total number of
      AciI sites in the analyzed fragments ranged from 2 to 7 for different genes. Only
      1 subject (2.1%) from the control group (healthy young individuals, age <= 35)
      has methylation of the studied CpG--dinucleotides of RASSF1A gene. Promoter
      methylation of at least one of the genes analyzed was observed in 28.92%
      liquidators and significantly exceeded (p = 0.016) such rate in a one-age (> 35
      years of age) control group (12.31%). A significantly elevated frequency (p =
      0.023) of individuals with abnormal methylation of GSTP1 gene in the group of
      liquidators as compared to the control group was revealed. The occurrence of
      promoter methylation of RASSF1A gene significantly correlated with aging both in
      the control group (r = 0.214; p = 0.023) and in the liquidators of the Chernobyl
      accident (r = 0.230; p = 0.036). No similar trend was found for other genes.
      Multiple regression analysis showed that the growth in the number of methylated
      loci of a set of genes p16, p14 and GSTP1 is exclusively due to the fact of
      exposure (OR = 7.32, 95% CI = 2.49-25.83, p-value = 2.7 x 10(-5)). The results
      obtained demonstrate for the first time the reality of the radiation-induced
      aberrant methylation of CpG islands in promoters of genes involved in the basic
      protective, functions of cells in the human body in remote periods after
      radiation exposure.

PMID- 25764815
TI  - [Biophysical modeling of dose response for gamma-ray induced complex chromosomal
      aberrations].
AB  - Experiments with FISH painting of chromosomes, including full-color mFISH, have
      revealed unexpectedly high yields of complex chromosomal aberrations (CA). The
      ratio of complex and simple aberrations observed in the 1st postirradiation
      mitosis has proved to depend on the cell line, LET and time after irradiation in
      a complicated way. According to the widely accepted viewpoint, interchanges are
      formed as a result of interaction between either contacting lesions or those
      having come into contact on a boundary between chromosome territories. However,
      the theoretical analysis has shown that the mechanism of CA formation at the
      boundary between chromosome territories is insufficient to explain the high ratio
      of complex/simple aberrations induced by gamma-rays in human lymphocytes at
      different doses. In the present work, the origin of high yields of complex CA is
      investigated by means of biophysical modeling. The hypothesis that CA are formed
      on nuclear centers is able to explain quantitatively the dose response
      relationships for both simple and complex interchanges observed by mFISH
      technique after low-LET irradiation.

PMID- 25764816
TI  - [Influence of chronic irradiation on the distribution of blood lymphocyte
      subpopulations among professionals of the atomic industry].
AB  - The aim of the study was to investigate the effects of chronic exposure to
      ionizing radiation on the cellular immunity of employees of the nuclear industry.
      Peripheral blood samples were studied in 195 employees of Physics and Power
      Engineering Institute (PPEI, Obninsk), who professionallycontacted with sources
      ofionizing radiation and were under individual dosimetric control. The median
      cumulative dose was 61.2 mSv, the average duration of work at the enterprise -27
      +/- 5 years. The control group consisted of 57 healthy individuals of a similar
      age and sex who did not have contact with sources of radiation. Indicators of the
      cellular immunity were determined by flow cytometry. Comparison of a cell
      mediated immunity was conducted separately in the two age groups (20-40 and 41-70
      years). The significant reduction inthe relative content of CD4+CD8 T-helper
      cells and the increase in the relative content of CD3-CD16, CD56+ NK-cells were
      found in both age groups of the PPEI employees in comparison with the age-matched
      control groups (p < 0.05). Separate analysis of the results in the low dose group
      (up to 50 mSv) demonstrated reducing the relative content of T-helper cells and
      increasing the proportion of NK-cells (as in the analysis of whole groups without
      taking into account the cumulative dose), as well as reducing the proportion of
      CD8+CD25+ activated lymphocytes in PPEI employees as compared to the age-matched
      control. Multiple regression analysis of the immunological parameters dependence
      on age and dose established a significant correlation of the relative content of
      CD3-CD19+ B-cells (r = -0.284, p = 2.9 x 10(-4)) and CD19+CD5+ B1-lymphocytes (r
      = -0.241, p = 0.002) with the dose of employees regardless of age, indicating the
      relationship of the changes in the B-cell component of immune system with the
      radiation factor.

PMID- 25764817
TI  - [Radiation-induced changes in structural state of membranes of human blood
      cells].
AB  - To evaluate radiation-induced changes in the structural state of the membranes,
      blood samples of healthy donors were subjected to gamma radiation in the range of
      small (1-10 cGy) and medium doses (50 cGy-2 Gy). After irradiation, the
      microviscosity of lipid membranes of red and white blood cells was measured by
      ESR spin probe method. At doses exceeding 1 cGy, statistically significant
      changes of the degree of spontaneous erythrocyte hemolysis and of the lymphocyte
      plasma membrane microviscosity were observed. Under identical irradiation
      conditions, the stability of lymphocyte membranes was less as compared to
      erythrocyte membranes.

PMID- 25764818
TI  - [Effect of dimethyl sulfoxide on the extent of DNA single-strand breaks and
      alkali-labile sites induced by 365 nm UV-radiation in human blood lymphocyte
      nucleoids].
AB  - It is shown that exposure of 365 nm UV radiation at doses of 10, 20 and 50 kJ/m2
      induces a dose-dependent increase in DNA single-strand breaks and alkali-labile
      sites (SSB and ALS) detected by comet and halo assays in human blood lymphocyte
      nucleoids. Adding 10% dimethyl sulfoxide (DMSO) reduces the SSB and ALS yields-
      in 3 times. A strong drop in the output of UV-A-induced SSB and ALS in lymphocyte
      nucleoids in the presence of DMSO shows the leading role of *OH radicals in this
      DNA damage formation under exposure to 365-nm UV-radiation.

PMID- 25764819
TI  - [Antioxidant enzyme activities in Scots pine populations growing under chronic
      radiation exposure].
AB  - The activities of superoxide dismutase, catalase and peroxidase in Scots pine
      populations growing in the contaminated areas of Bryansk region were
      investigated. The dose rate at the experimental sites ranged from 7 to 130
      mGy/year. It has been identified that the activities ofantioxidant enzymes do not
      depend on the radiation factor under these dose rates. These doses were found to
      be insufficient for forming significant physiological effects.

PMID- 25764820
TI  - [Embryogenesis of the Japanese quail in hypomagnetic conditions applied to deep
      space flights].
AB  - During future interplanetary flights and on the lunar base, astronauts and
      bioregenerative systems on the space ship will occur in an interplanetary
      magnetic field, which is much lower than the habitual geomagnetic field (GMF). It
      is known that hypomagnetic conditions have an adverse biological effect on human
      beings and other living systems. In our research the Japanese quail has been
      chosen as one of the possible elements of the bioregenerative live support
      system. The magnetic system--Helmholtz's coils--is used for compensation of GMF.
      The GMF in the center of Helmholtz's coils was decreased to 80-100 times. The
      eggs were kept under hypomagnetic conditions for 4 and 10 days in a special
      nonmagnetic incubator. The experiments have demonstrated a negative influence of
      hypomagnetic fields on the embryo development of the Japanese quail. One of the
      possible ways to solve the problem consists in installing special magnetic
      systems onboard the interplanetary ship and a lunar base. Evidently, it is
      necessary to create an analogue of GMF for bioregenerative live support systems.

PMID- 25764821
TI  - [State of the reproductive systemin in male rats of 1st generation obtained from
      irradiated parents and exposed to electromagnetic radiation (897 MHz) during
      embryogenesis and postnatal development].
AB  - The consequences of prolonged exposure to electromagnetic radiation from cellular
      phone (897 MHz, daily 8 h/day) in male rats of the 1st generation obtained from
      irradiated parents and subjected to prolonged exposure to electromagnetic
      radiation of the range of mobile communications during ontogeny and postnatal
      development were studied. It has been found that irradiation causes a decrease in
      the number of births of animals, changing the sex ratio towards the increase in
      the number of males. It had a significant impact on the reproductive system of
      males, accelerating their sexual development, revealed at the age of two months.
      Radiation from cell phones led to significant disproportions in the cell number
      at different stages of spermatogenesis. It increased the number of mature
      spermatozoa which decreased viability.

PMID- 25764822
TI  - [About the contents of 40K, 226Ra and 232Th in forest soils of the Republic of
      Belarus].
AB  - The specific activity of 40K, 232Th and 226Ra in forest soil ecotopes (A2-B2-C2
      D2) has been investigated. When the fertility of the soil increases from A2 to
      D2, then the specific activity of 40K increases in the rooting zone of the soil
      from 275 +/- 6.9 up to 499 +/- 11 Bq/kg, 232Th--from 11.8 +/- 0.5 to 17.1 +/- 1.1
      Bq/kg, 226Ra- from 19.2 gamma 0.8 to 27.9 +/- 1.5 Bq/kg. The calculated capacity
      of the absorbed dose of gamma-radiation conditioned by 40K, 232Th and 226Ra
      increases from A2 to D2 from 27.5 +/- 0.5 to 44.1 +/- 1.1 nGy / h at the height
      of 1 m.

PMID- 25764823
TI  - [The assessment of the content of 137Cs of the global and Chernobyl origin in
      forest soils and some types of edible fungi].
AB  - The article analyzes the density of pollution of the soil by radioisotopes of
      caesium and the content of 137Cs in fruit bodies of some species of forest
      mushrooms on the "long" trail of radioactive fallout in the Republic of Belarus
      in 1994 and 2012. On the basis of the calculated density of pollution of the soil
      with 134Cs in 1986 the contribution to the total density of pollution with 137Cs
      of the global radioactive fallout and emissions owing to the accident at the
      Chernobyl nuclear power plant was defined for the studied territory. It was
      established that at the density of pollution of the soil by 137Cs of 12-19 kBq/m2
      in 1986 about 35% of pollution was caused by the global radioactive fallout. In
      1994 and 2012, a specific activity and transfer factor of 137Cs were analyzed for
      fruit bodies of some species of forest mushrooms. The transfer factors of 137Cs
      for fruit bodies of Boletus edulis are at level of 10 x 10(-3) m2/kg, Leccinum
      scabrum and Leccinum aurantiacum - (15-20) x 10(-3) m2/kg, Xerocomus badius--(60
      80) x 10(-3) m2/kg.

PMID- 25764824
TI  - [Future development of radioecological investigations--new international
      projects].
AB  - Information is given on the future development of nuclear power engineering and
      the need to ensure environmental safety. The complexity of the emerging problems
      requires a wide international integration of scientific investigations. Also
      described are ecological projects that have been implemented by the IAER after
      the Chernobyl NPP accident, as well as a new project, MODARIA, which will pay
      special attention to the improvement of models for radionuclide transfer and
      estimation of radiation effects on both humans and biota. The strategy and agenda
      for the development of radioecological studies in the 21st century are described
      which are being realized by the nine key research centers (European Radioecology
      Alliance) under the EC project STAR.

PMID- 25764825
TI  - [Mobile phone and adverse effects on the user's brain--assessment and risks].

PMID- 25764826
TI  - [International Conference "Radiobiological Problems of Radiation Therapy of
      Tumors" (Moscow, 19-20 November, 2013)].

PMID- 25764827
TI  - [On the prospects of using the DNA repair inhibitors in radiotherapy of tumors].
AB  - The cellular DNA repair systems sufficiently provide the resistance of tumors to
      ionizing radiation, and thus contribute to reducing the effectiveness of their
      radiotherapy. Therefore, suppression of the activity of critical DNA repair
      enzymes in tumor cells is considered one of the promising directions to overcome
      this resistance. As can be seen from the literature analysis, the use of many
      inhibitors of DNA repair enzymes have not yet yielded the results, which can be
      extrapolated to preclinical models or clinical trials. However, experimental
      studies show that the inhibitors of the enzyme family of poly(ADP-ribose)
      polymerases (PARP) are able to inhibit the growth of various human tumor cells.
      Pre-clinical and clinical trials of the PARP inhibitors also show promising
      results in terms of the possibility of their wide practical application. The
      effect of the PARP inhibitors consists in the blockage of the most important DNA
      repair systems. This leads to the accumulation of DNA single-strand breaks, the
      collapse of replication forks and to generation of lethal double-strand breaks
      (DSB). The PARP inhibitors can be used to suppress breast cancer and ovarian
      cancer with mutations in BRCA-1/2 genes ("BRCAness" cancer) without combination
      with radiotherapy or chemotherapy. In the tumor cells deficient in BRCA-1/2 genes
      DSB repair by homologous recombination pathway does not function. Therefore, the
      process of DNA DSB repair is switched to the non-homologous end-joining pathway,
      which operates with formation of the chromosomal rearrangements leading to cell
      death. Thus, the analysis results show that DNA repair inhibitors have the
      potential to improve the efficiency of cancer radiotherapy. Further research in
      this direction is very promising.

PMID- 25764828
TI  - [Radiobiological dependences of normal tissue reactions in radiation therapy for
      tumors].
AB  - The new ICRP recommendations (Publication 118) are devoted to reactions of human
      tissues to acute, chronic and fractionated radiation. It is currently obvious
      that the reactions of tissues to ionizing radiation exposures are predetermined
      not only by the dose and dose rate, they may be altered under the impact of
      multiple biological modifiers (antioxidants, cytotoxins, growth factors etc.),
      are dependent on the age, initial state of the tissues, organs, and the genetic
      characteristics of the patient's organism. The manuscript addresses the
      mechanisms inducing tissue reactions to irradiation, and presents the current
      estimates of dose threshold values for the tissue reactions associated with
      fractionated irradiation. It has been noted that fractionated irradiation
      induces, as a rule, less manifested effects compared to those induced by equal
      doses of acute irradiation. For the first time, the threshold doses for induction
      of cardio-vascular and cerebrovascular diseases have been estimated. The
      thresholds doses for cataract induction have been revised. A considerable
      attention has been given to tissue reaction modifiers which are represented by
      different groups of compounds, and can be used as prophylactic, palliative or
      remedial agents in radiation therapy.

PMID- 25764829
TI  - [Increase in the number of cancer stem cells after exposure to low-LET
      radiation].
AB  - Radioresistance of cancer stem cells (CSCs) is regarded as one of the possible
      causes of cancer recurrence after radiotherapy. Since the regularities and
      mechanisms of radiation effects on this population of cells have not been
      sufficiently studied, the aim of this work is to elucidate the changes in the CSC
      number after gamma-irradiation in stable cultures of tumor cells in vitro and
      tumor tissue in vivo (in the course of radiation therapy of patients with cancers
      of the upper respiratory tract). CSCs were identified in the cell lines B16, MCF
      7, HeLa by the ability to exclude the fluorescent dye Hoechst 33342 (SP method)
      48-72 h after irradiation at the doses of 1-20 Gy and in biopsy material by
      immunophenotype CD44+CD24(-/low) before and 24 h after irradiation at the total
      dose of 10 Gy. The essential differences in the response of CSCs and other cancer
      cells were found after exposure to low-LET radiation. The absolute number of CSCs
      increased after a single exposure at the doses ranging from 1 to 5-10 Gy in
      different cell cultures, but a further dose increase maintained the current
      number of CSCs or decreased it. At the same time, the number of non CSCs
      significantly decreased with increasing doses of radiation exposure, as expected.
      Fractionated irradiation in vivo at a total dose of 10 Gy increased the relative
      amount of CSCs in most patients. The registered changes are an integral indicator
      of cell death, cell division delay immediately after irradiation, proliferation
      at a later time, possible dedifferentiation of non CSCs, etc. The exact
      contribution of each of them to the radiation-induced increase of the CSCs number
      is of considerable interest and requires further research.

PMID- 25764830
TI  - [The effectiveness of molixan as a means of correction of chemoradiation therapy
      negative manifestations in patients with oropharyngeal cancer].
AB  - The effectiveness of the peptide immunomodulator molixan as a means of support
      and correction of chemoradiation therapy of oral mucositis have been studied in
      36 patients with primary regional cancer of the oral mucosa and the oropharynx.
      Combined chemotherapy of patients with cisplatin and standard radiotherapy was
      associated with progression of oral mucositis and hematopoietic disorders which
      manifested themselves in the form of neutro-, lympho- and thrombocytopenia.
      Therapeutic intramuscular application of molixan at a dose of 60 mg once a day
      after a fraction of irradiation made it possible to reduce the severity of oral
      mucositis (from grade III-IV to grade I-II), as well as to maintain in patients a
      higher level of white blood cells and platelets in the blood, which made it
      possible to complete the planned course of chemoradiation therapy.

PMID- 25764831
TI  - [Are the properties of peripheral blood lymphocytes of patients with prostate
      cancer connected with the efficiency of radiation therapy?].
AB  - The genome damage (frequency of cells with micronuclei and chromosome
      aberrations), concentration of reactive oxygen forms (ROS), markers of
      lymphocytes activation, expression of proliferation (CD69, Ki67) and proapoptotic
      antigen (CD95), as well as the ability to adaptive response have been
      investigated in blood lymphocytes of healthy donors and patients with prostate
      gland cancer. The influence of hormone-therapy on lymphocytes properties and
      connection between the parameters studied with the effectiveness of treatment,
      which was estimated by the level of prostate specific antigen (PSA), have been
      investigated. It was discovered that the genome damage to the patients with
      prostate gland cancer lymphocytes does not differ from control. The increase of
      the ROS level and decrease of radiosensitivity (irradiation of isolated
      lymphocytes in vitro at a dose of 1 Gy) are observed but they are insignificant.
      The content of the cells expressing CD69 and CD95 markers doesn't change but the
      expression of proliferative activity marker Ki67 in cells decreases.
      Radiosensitivity of lymphocytes in patients with prostate gland cancer correlates
      with the CD95 markers expression--a higher radio sensitivity points to their
      predisposition to apoptotic death. The expression of the markers studied depends
      on the oxidative status--a high ROS level suppresses their expression. The
      hormone therapy applied before radiotherapy leads to the increase in
      radiosensitivity and decrease in ROS. As the MN test shows, the ability to
      adaptive response of the lymphocytes in patients with prostate gland cancer is
      increased as compared with lymphocytes of healthy donors but it is insignificant;
      moreover, hormones do not influence the ability to the adaptive response. The
      high oxidative status further the formation of the adaptive response. We suppose
      that the discovered correlation between the initial, before treatment, frequency
      of lymphocytes with micronuclei and treatment effectiveness, namely, the
      decreased number of damaged cells associated with the treatment efficiency, is
      very important for the treatment prognosis. The results obtained can be very
      important for the experimental justification and understanding a possible use of
      blood lymphocytes for the additional diagnostics of prostate gland cancer and
      prognosis for its successful treatment.

PMID- 25764832
TI  - [The frequency and spectrum of cytogenetic anomalies in employees of Siberian
      Group of Chemical Enterprises].
AB  - The results of the study of frequency and spectrum of cytogenetic anomalies in
      657 healthy employees of the main facilities of the Siberian Group of Chemical
      Enterprises exposed to external, internal and combined irradiation are presented.
      No dependence between age and chromosome aberrations frequency was revealed.
      Chronic external exposure appeared to be the main factor of induction of
      chromosome aberrations. The frequency of aberrant cells, chromosome type
      aberrations, paired fragments and rings was statistically significantly higher in
      employees exposed to external irradiation as compared to persons exposed to
      combined irradiation. A nonlinear dependence the dose of irradiation and
      frequency of chromosome aberrations was revealed. A statistically significant
      decrease of prevalence of aberrant cells, aberration of chromatid and chromosome
      type was established in employees exposed to irradiation at a dose range of > 0
      10 mSv compared to the control group. This agrees with the phenomenon of
      radiation hormesis. A significant increase of the frequency of chromosome
      aberrations was not observed at doses below > 40 mSv. In employees exposed to
      irradiation at a dose range > 40-100 mSv, a statistically significant increase of
      frequencies of aberrant metaphases, aberrations of chromatid and chromosome types
      was established. Same was found for dicentrics at dose range of >100-200 mSv.
      This supports a well known linear threshold model. Dose-effect curve has a
      plateau at doses ranged from 100 to 500 mSv.

PMID- 25764833
TI  - [Research on structural and functional characteristics (indicators) of apoptosis
      of human blood lymphocytes under the influence of carbon monoxide and ultraviolet
      (UV)-radiation].
AB  - The changes in the level of expression of membrane CD95 receptor, the structural
      state of DNA, parameters of biochemiluminescence of human blood lymphocytes under
      conditions of exposure to carbon monoxide (60-90 min) and UV-radiation (240-390
      nm) at the doses of 151, 453 and 755 J/m2 have been investigated. The decrease in
      the level of expression of Fas-markers on the surface of immunocytes after
      incubation in the atmosphere at (60-90 min), the absence of changes in the DNA
      structure and the decreased intensity of lipid peroxidation processes in the
      cells were also found. It is established that UV-light (151-755 J/m2) exhibits a
      proapoptotic action, as evidenced by the increase in the expression of CD95
      receptors on the surface of human blood lymphocytes and the decreased
      electrophoretic mobility of DNA in UV-irradiated cells. However, the process of a
      programmed cell death is not leaking ("apoptotic ladder" on electrophoregramme in
      the conditions of the experiment is missing). It is shown that the combined
      effects of carbon monoxide and UV-light in the cells of the human blood leads to
      a decrease in the sensitivity of the membrane CD95 receptors to the action of UV
      radiation. It is revealed that carbon monoxide can contribute to blocking the
      processes of peroxide oxidation of lipids (POL) and, as a consequence, activate
      antioxidant properties of cells. It was concluded that the CO molecule in
      physiological concentrations is likely to have the antiapoptotic effect in
      relation to lymphocytes.

PMID- 25764834
TI  - [Free-radical reactions in Daphnia after low doses of gamma-irradiation in vivo].
AB  - A violation of free-radical reactions has been found by the method of free
      radical copolymerization in the two groups of Daphnia magna exposed to 100 and
      1000 mGy of gamma-rays and their non-exposed first generation progeny. The method
      is based on a quantitative radiometric registration of the polymerization process
      that develops in the cells of a multicellular organism in tissue in proportion to
      the existing number of free radicals. The fact of the increased level of free
      radicals may be indicative of the hereditary transgenerational effect and the
      cause of lower survival of Daphnia in both generations. However, the effect of a
      reduced survival rate does not persist in the second generation, which can be
      explained by the effect of radiation on the embryos of the first generation after
      acute irradiation of parents.

PMID- 25764835
TI  - [New facts in favor of the absence of genomic instability induced by low doses of
      low LET radiation and conclusions about the threshold effect reported in the
      UNSCEAR-2012 recommendations].

PMID- 25764836
TI  - [The main findings of research conducted in radiation biology and radiation
      ecology in 2013].

PMID- 25764837
TI  - [XLII V. M. Klechkovski readings on radiology].

PMID- 25764838
TI  - [Results of the 2nd international research paper competition on the environmental
      impact of nuclear power].

PMID- 25764839
TI  - [In memory of Yuri A. Izrael (15.05.1930-23.01.2014)].

PMID- 25764840
TI  - [Radiation biology of structurally different Drosophila genes. Report V. The
      cinnabar gene: general and molecular characteristics of its radiomutability].
AB  - The results of the genetic, cytogenetic and molecular analysis of the recessive
      mutations at the small, lying close to the centromere, cinnabar (cn) gene of
      Drosophila melanogaster induced by gamma-rays of 60Co (doses 5-60 Gy) or 0.85 MeV
      fission neutrons (doses 2.5-20 Gy) in the mature sperm of the wild-type males
      from the laboratory line D32 are presented. The whole spectrum of the cn
      mutations induced by different quality radiation is found to be the same and
      consists of the two main-distinct classes such as gene/point and gene/chromosome
      mutations either of which includes the array of the subclasses (gene/point simple
      or complex mutations and chromosome rearrangements detected as F1 cn mutants with
      dominant sterility of multilocus deletions involving the cn gene wholly). The
      induction rate of both mutation classes is found to be increased linearly with
      dose of low- and high-LET radiation and the RGE values of neutrons are 1.0 and
      4.0 for the gene/point and gene/chromosome mutations respectively. According to
      the data of the molecular analysis, 28 out of 59 (47.5%) gamma-ray- and neutron
      induced gene/point cn mutations studied are found to have the intragenic DNA
      alterations detected by PCR technique as a loss of the single or two adjacent
      fragments-amplicons non-randomly located at the 5'- or 3'- end of the gene map.
      Essentially, 10 out of 48 (20.8%) gamma-ray-and 3 out of 11 (27.3%) neutron
      induced gene/point mutations are found to show the same molecular "phenotype"
      (the loss of the two adjacent fragments at the 3'- end of the gene map) as that
      in the cn1 allele-marker from the maternal tester-line KL with the females of
      which the irradiated males were crossed. Among the putative recombination-based
      genetic processes underlying the exchange between the cn1 and damaged cn(+32)
      alleles, the gene conversion in the "gonomeric" nucleus of the zygote seems to be
      the most likely such processing. The established features of the cn gene
      radiomutability are compared with those earlier described for the other small
      gene black+ located in the middle of the 2L chromosome.

PMID- 25764841
TI  - [Modification of the cytogenetic effects of irradiation by water with the reduced
      content of deuterium and heavy isotopes of oxygen].
AB  - The influence of light water with the reduced content of heavy stable isotopes of
      oxygen and hydrogen (deuterium) on the cytogenetic status of irradiated animals
      was investigated. In mice, hybrids of the first generation (CBA x C57B1) F1, the
      increase in the output (two-fold at the dose of 2 Gy) of aberrant mitoses in the
      cells of bone marrow and the decrease in the duration of the mitotic index of the
      first cellular cycle occurred under the influence of the two week maintenance
      before the irradiation on light water with ppm 35 obtained by the method of
      rectification as compared with the irradiated animals that were kept on the
      distilled water. It has been discovered that 24 h after irradiation the number of
      leukocytes in the group which consumed light water is lower than that in the
      animals that were contained on the distilled water. Moreover, the cellularity of
      the bone marrow in the group which consumed light water was higher than that in
      the animals that were contained on distilled water. The prolonged application of
      light water before irradiation (for 14 days) led to an increase in the
      sensitivity of the chromosomal apparatus of mice to gamma-irradiation against the
      background of an increase in the mitotic activity of cells.

PMID- 25764842
TI  - [Peculiar features of forming radiation effects in inbred populations of
      Drosophila melanogaster differing in cytotype].
AB  - A comparative evaluation of the sensitivity of inbred wild-type flies differing
      in the cytotype to the action of low-intensity radiation of different duration
      was conducted taking into account the integral parameters of survival. The strong
      dependence of the frequency of radiation-induced DNA damage (in the neutralpH
      version) to the cells of individuals on the dose of low-intensity radiation and
      stages of spermatogenesis was established. The hyper-radiosensitivity was found
      in the individuals of Charolles (R-cytotype), Harwich (P-cytotype), and Oregon-R
      (H-cytotype) strains irradiated during the early stages of spermatogenesis
      (spermatogonia-spermatocytes) and containing in their genotype transposons Bari
      1, P and hobo, respectively. While drosophila line Canton-S exhibited dysgenetic
      properties against the background of several cytotypes (E, I and M), the effect
      of hormesis was identified under the same experimental conditions. With the
      increase in the dose of low-intensity irradiation, the frequency of the DNA
      damage either increased (for Canton-S) or reduced (for Harwich and Charolles). At
      that, the profile of fertility and. survival of wild-type stocks studied was
      maintained at a significantly high level. The important role of the cytotype and
      mobile genetic elements responsible for its formation in the modification of the
      effects of low-intensity gamma-radiation is shown.

PMID- 25764843
TI  - [Effect of prolonged administration of low doses of essential oils on the immune
      response and sensitivity of mice to the action of ionizing radiation].
AB  - The effect of ionizing radiation (1 Gy) on the immunological characteristics of
      spleen in the mice that consumed essential oils of oregano, clove bud and the
      mixture of lemon oil with ginger extract at low doses with drinking water for 6
      months was studied. It was found that the essential oils increased the content of
      antibody forming lymphocyte cells in the spleen. The maximal effect in comparison
      with control was found for essential oil of clove bud.

PMID- 25764844
TI  - [Natural purine compounds as radioprotective agents].
AB  - Purine compounds xanthosine, caffeine, inosine-5'-monophosphate and guanosine-5'
      monophosphate in the concentration range of 0.02-1 mmol/L exhibit antioxidant
      properties in vitro, significantly reducing the formation of hydrogen peroxide
      and hydroxyl radicals induced by X-rays in aqueous solutions and preventing the
      formation of 8-oxoguanine in DNA solutions. These compounds neutralize the long
      lived protein radicals in vitro induced by radiation. In vivo they exhibit
      pronounced radiotherapeutic properties, increasing the survival rate of mice up
      to 50% by intraperitoneal injection (45 mg/kg) after the exposure to a lethal
      dose of 7 Gy. The tested compounds stimulate hemopoiesis, increasing the number
      of white blood cells and platelets in the peripheral blood of animals in
      postradiation period, as well as radiation recovery of DNA damage when
      administered both before and after irradiation. These purine compounds can be
      considered as potentially promising preventive and therapeutic agents to reduce
      the risk of the pathological effects of ionizing radiation on the body of
      mammals.

PMID- 25764845
TI  - [Influence of indoinetophene on the antiradiation properties of indralin].
AB  - Radioprotective properties of indralin were studied at its combined
      administration with indometophene in the periods optimal for each preparation
      before acute radiation exposure. Animals were subjected to total radiation on the
      IGUR installation (137Cs): mice of the strain (CBA x C57B1) F1 at a dose of 9 Gy
      (LD100/30), purebred dogs--4 Gy (LD100/45). It was established in the experiments
      on mice that considerable radioprotective effect can be obtained by the use of
      indralin at a dose that is half the optimal radioprotective dose if it is applied
      against the background of indometophene administered at its optimal
      radioprotective dose four days before. The survival of mice increased on the
      average by 30-35% and provided the same effect of protection as a single indralin
      at the optimal radioprotective dose (100 mg/kg). The survivability of dogs after
      the combined application of the two radioprotectors makes up 43% against 14%
      after application of only indralin at a dose of 5 mg/kg (half the optimal
      radioprotective dose). Indometophene, along with strengthening the antiradiation
      activity of indralin at the ineffective (half the optimal) dose, allows the
      reduction of its undesirable postradiation effects in the hemopoietic tissue. The
      important role in the mechanism of the antiradiation activity of indometophene
      and indralin belongs to the increased ribonucleotide reductase activity and
      induction of the ribonucleotide synthesis that provides effective reparation of
      the damage to the DNA of the cells in radiosensitive tissues and organs as a
      result of administration of protective doses of radioprotectors at the optimal
      doses before radiation exposure.

PMID- 25764846
TI  - [Theoretical and experimental dosimetry in evaluation of biological effects of
      electromagnetic field for portable radio transmitters. Report 1. Flat phantoms].
AB  - Results of the theoretical (numerical) and experimental dosimetry approach for
      portable radio transmitters are considered. The simulation and measurement
      results are shown. A generic type of a portable radio transmitter operating in a
      very high frequency range was tested as an electromagnetic field source. The
      analysis of specific absorption rate distribution in the flat homogeneous phantom
      was carried out on the basis of a portable radio transmitter. The results have
      shown the admissible divergence between measurements and simulation. According to
      these results, the authors have come to the conclusion about using the complex
      dosimetry approach including experimental and numerical dosimetry.

PMID- 25764847
TI  - [Change settings for visual analyzer of child users of mobile communication:
      longitudinal study].
AB  - The paper represents theresults of longitudinal monitoring of the changes in the
      parameters of simple visual-motor reaction, the visual acuity and the rate of the
      visual discrimination in the child users of mobile communication, which indicate
      the multivariability of the possible effects of radiation from mobile phones on
      the auditory system of children.

PMID- 25764848
TI  - [Distribution of 137Cs, 90Sr and their chemical analogues in the components of an
      above-ground part of a pine in a quasi-equilibrium condition].
AB  - The additional study of the distribution of radioactive isotopes of caesium and
      strontium and their chemical analogues in the above-ground components of pine in
      the remote from the accident period was carried out. The results of the research
      confirmed the existence of analogy in the distribution of these elements on the
      components of this type of wood vegetation in the quasi-equilibrium (relatively
      radionuclides) condition. Also shown is the selective possibility of using the
      data on the ash content of the components of forest stands of pine and oak as an
      information analogue.

PMID- 25764849
TI  - [Man-made radionuclides and their accumulation by plants of different taxonomic
      groups from the soils of the eastern ural radioactive trace].
AB  - Investigations of the spatial and vertical distribution of 90Sr, 137Cs and 239,
      240Pu in the soils of the Eastern Ural Radioactive Trace (EURT) and accumulation
      of these radionuclides by plants were carried out in 2003-2011. Investigations
      showed that the spatial distribution of the radionuclides with increasing
      distances from the epicenter of the accident is satisfactorily approximated by
      the exponential function. During the post-accidental period the essential amount
      of radionuclides is located in the 15-20 cm root layer of the soil. Uptake by
      plants of 90Sr is determined, first of all, by the level of the soil
      contamination. For 137Cs, reliable differences in its accumulation ability
      between representatives of the higher plants and lower ones are remained in the
      whole gradient of contamination.

PMID- 25764850
TI  - [Evaluation of the partial contribution of naturally occurring radionuclides and
      nonradioactive chemically toxic elements in formation of biological effects
      within the Vicia cracca population inhabiting the area contaminated with uranium
      radium production wastes in the Komi Republic].
AB  - The site contaminated with uranium-radium production wastes in the Komi Republic
      was studied. The activity concentration of naturally occurring radionuclides
      (226Ra, 228Th, 238U, 230Th, 232Th, 210Po, and 210Pb), as well as concentrations
      of nonradioactive chemically toxic elements (Pb, Zn, Cu, As, V, Mo, Sr, Y, and
      Ba) in the soil samples from the experimental site is 10-183 times higher than
      reference levels. A chronic exposure to alpha-emitters and nonradioactive
      chemically toxic elements causes adverse effects in tufted vetch (Vacia cracca
      L.) both at the cellular (aberration of chromosomes) and population (decrease in
      the reproductive ability) levels. Radionuclides are the main contributors to the
      decrease in the reproductive capacity and an increase in the level of the
      cytogenetic damage in root tip cells of tufted vetch seedlings. As and Pb
      significantly influence the reproductive capacity of plants. Sr, Zn, Y and P
      modify the biological effects caused by exposure to radionuclides. Moreover, P
      and Zn reduce the adverse effects of radionuclides; however, Sr and Y enhance
      these effects.

PMID- 25764851
TI  - [Assessment of cyto- and genotoxicity of natural waters in the vicinity of
      radioactive waste storage facility using Allium-test].
AB  - Efficacy of bioassays of "aberrant cells frequency" and "proliferative activity"
      in root meristem of Allium cepa L. is studied in the present work for a cyto- and
      genotoxicity assessment of natural waters contaminated with 90Sr and heavy metals
      in the vicinity of the radioactive waste storage facility in Obninsk, Kaluga
      region. The Allium-test is shown to be applicable for the diagnostics of
      environmental media at their combined pollution with chemical and radioactive
      substances. The analysis of aberration spectrum shows an important role of
      chemical toxicants in the mutagenic potential of waters collected in the vicinity
      of the radioactive waste storage facility. Biological effects are not always
      possible to explain from the knowledge on water contamination levels, which shows
      limitations of physical-chemical monitoring in providing the adequate risk
      assessment for human and biota from multicomponent environmental impacts.

PMID- 25764852
TI  - [ICRP report on tissue responses to the effects of ionizing radiation in the
      context of radiation protection (ICRP Publication 118)].

PMID- 25764853
TI  - [Cellular communications and public health. Moscow: Economics, 2013. 556 pp].

PMID- 25764854
TI  - [In memory of Anatoly Fyodorovich Tsyb].

PMID- 25764855
TI  - [The legal and forensic medical problems related to the determination of
      viability of the fetuses and newborn infants under the present-day conditions].
AB  - The authors consider from the historical and methodological standpoints the
      problem of the determination and expert evaluation of viability of the fetuses
      and newborn infants in the case of expert examination of their corpses and
      performance of complicated forensic medical expertises concerned with medical
      aspects of obstetric practice. It was shown that the new medical criteria for
      birth introduced in 2013 pose the question of their relation to the known signs
      of viability of the fetuses and/or newborn infants and the necessity of further
      substantiation of such point of view for taking the correct legal decision.

PMID- 25764856
TI  - [The general and individual characteristics of the liver ruptures in the case of
      a blunt injury to the chest and abdomen].
AB  - The present study is based on the results of analysis of 150 cases of the fatal
      blunt injury to the chest and abdomen associated with liver rupture for the
      purpose of systematization of practical and experimental data concerning this
      issue. Special attention is given to the diagnostic signs of local major
      (primary) and additional (secondary) lesions localized at the sites of force
      application and their long-term consequences. The diagnostic forensic medical
      criteria are proposed allowing to characterize hepatic injuries depending on the
      mechanism and conditions of their infliction in different situations.

PMID- 25764857
TI  - [The prospects for the study of the wound canals in the chest].
AB  - The objective of the present study was to develop the method for the
      determination of the position of the upper extremities at the moment of formation
      of the punctured-incised wounds in the chest canals taking into consideration
      peculiarities of their structure. A few series of experiments carried out for
      this purpose involving different positions of the upper extremities made it
      possible to evaluate the degree of displacement of the tissues in different chest
      regions and characterize disjunctive (disruptive) dislocation of the wound
      canals. The reconstruction of rectilinearity of the chest channel made it
      possible to demonstrate the possibility of establishing the initial position of
      the upper extremity at the moment of infliction of injury. The validity of the
      results of the study is illustrated by the example of practical forensic medical
      expertise.

PMID- 25764858
TI  - [A sign of the rotational impact of the gunshot projectile on the flat bone].
AB  - The objective of the present work was to study the mechanisms of formation of the
      gunshot fracture of the flat bones with special reference to the translational
      and rotational motion of the projectile. A total of 120 real and experimental
      injuries of this type were available for the investigation with the use of
      simulation by the finite-elemental analysis. A set of morphological features has
      been identified that make it possible to determine the direction of rotation of
      the gunshot projectile.

PMID- 25764859
TI  - [Forensic medical peculiarities of mechanical strangulation asphyxia in the
      hanged subjects aged above 50 years].
AB  - This paper presents the qualitative and quantitative characteristics of the
      morphological manifestations of mechanical strangulation asphyxia in the hanged
      subjects aged 50 years and the elder ones. In addition, the new diagnostic
      approaches to the expert confirmation of this condition are proposed.

PMID- 25764860
TI  - [The evaluation of the prospects for the application of mass-spectrometric
      analysis of the amplified DNA fragments for the purpose of forensic medical
      expertise].
AB  - The objective of the present study was to evaluate the prospects for the
      application of the mass-spectrometric analysis for the solution of the problems
      facing modern forensic-medical genetics as illustrated by the example of the new
      experimental multiplex approach to the typing of human DNA with the use of the
      complex PLEX-ID platform. The validation study involved all stages of the
      processing chain. The results of the study were used to develop the
      recommendations for the optimization of the analytical system being used. The
      comparative analysis of the experimental PLEX-ID technology and the traditional
      electrophoretic system for the analysis of polymorphism of amplified DNA
      fragments has demonstrated the potential advantages of the mass-spectrometric
      technique, such as the enhanced informative value of the forensic expert
      evaluation of polymorphism of STR-loci due to the possibility of identifying SNP
      and extension in them and therefore their allelic spectrum.

PMID- 25764861
TI  - [The evaluation of stability of blood stains immobilized on the FHA cards during
      their prolonged storage].
AB  - We have studied the samples of dry blood immobilized on the FTA cards following a
      15-year period of their storage at room temperature. The DNA preparations were
      obtained based on the protocol recommended by the manufacturer including washing
      up with the FTA reactant and in parallel by means of complete extraction with the
      use of robotic stations. The preparations were compared in terms of the content
      of amplificationally active DNA and the effectiveness of typing STR-loci of
      chromosomal DNA. The complete genetic profile was derived only from 41 (82%) of
      the 50 FTA cards with immobilized blood samples available for the investigation
      that had been treated with the FTA reactant and stored during 15 years at room
      temperature. In 9 (18%) cases, incomplete genetic profiles were obtained that
      were characterized by the absence of PCR-products, as well as missing of true
      alleles and the presence of pseudoalleles. Such poor results are supposed to be
      attributable to the occurrence of the residual inhibitors of DNA-polymerase
      activity due to the incomplete purification of the samples. This disadvantage was
      overcome by the application of robotic stations for the total DNA extraction.
      This approach made it possible to obtain the acceptable genetic profiles for each
      blood samples stored at the FTA cards during 15 years. Nevertheless, even these
      preparations exhibited the reduced matrix activity of high molecular weight SRT
      loci. This observation suggests that long-term storage of dry blood samples on
      FTA cards at room temperature does not guarantee the absence of degradation of
      their DNA.

PMID- 25764862
TI  - [Certain specific features of the imprints of the blood-saturated head hair].
AB  - The present experimental study revealed a number of morphological features of the
      imprints of head hair of different length (varying from 0.5 to 24 cm). The
      imprints were shown to have a complicated many-component structure in which it
      was possible to distinguish between the central and peripheral portions. The
      peripheral part of the hair imprints varying in length fromn 0.5 to 2.0 cm had
      the shape of the elongated triangles or arrowheads. The imprints of longer hair
      were shaped as arcuate or linear stripes. It is concluded that the above
      morphological features of blood-saturated hair can be used during examination of
      the scene of action or performance of other forms of forensic medical expertise.

PMID- 25764863
TI  - [Group polymorphism and variability of dermatoglyphic characters of the toes and
      fingers: the comparative characteristic].
AB  - The objective of the present study was to investigate into the morphological
      features of the papillary relief on the toes depending on the age and sex of the
      adult people and the length of their body and to compare the data obtained with
      dermatoglyphic patterns of the hands. Fingerprints of 120 male and 80 female
      central European caucasoids varying in age from 18 to 83 years were studied. The
      fingerprints were obtained using black printing ink. Special attention was given
      to the recognition of pattern types, ridge count, rudiments of lines, line
      density, the distances between the delta and the centre of the pattern or the
      interphalangeal fold, white lines, scar prints, and other characteristics. The
      results of the study were treated by the methods of descriptive statistics and
      correlation analysis. It was shown that coefficients of correlation between the
      most informative characters and the general personality traits are equal to 0.3
      0.4. The regular features of group polymorphism of dermatoglyphic patterns on the
      toes and fingers were found to be on the whole similar. The correlation
      coefficients between dermatoglyphic signs on the bilateral and homolateral halves
      of the body were 0.6-0.8 and 0.2-0.4 respectively. It is concluded that the
      results of this study provide a basis for the development of the methods for the
      detection of the general personality traits and the establishment of belonging of
      the cut-off feet and hands to one or several corpses.

PMID- 25764864
TI  - [Determination of olanzapine in cadaveric blood].
AB  - The authors present the results of experimental isolation of olanzapine from the
      biological objects in conjunction with the detailed description of the method for
      olanzapine extraction from cadaveric blood with the use of one of the amphiphilic
      solvents (e.g. acetone), purification by solvent extraction, and TLC-screening.
      Olanzapine was quantitatively determined by UV-spectrophotometry following its
      chromatography and elution. It was shown that one-step extraction from cadaveric
      blood by the proposed method made it possible to detect 55% of the total
      olanzapine content. The method was validated in the studies of blood and liver
      from the laboratory animals (rats) and can be recommended for the investigation
      in a chemical toxicological laboratory.

PMID- 25764865
TI  - [Specific features of the distribution of 2,4- and 2,6-dimethyl derivatives of
      hydroxybenzene in the body of the warm-blooded animals].
AB  - This study was designed to elucidate the specific features of the distribution of
      2,4- and 2,6-dimethyl derivatives of hydroxybenzene in the body of the warm
      blooded animals (rats) after the intragastric administration of these poisonous
      substances. It was shown that large amounts of these compounds are present in the
      unmetabolized form in the blood and internal organs of the experimental animals.
      Their largest quantities were found in the stomach contents, spleen, and small
      intestines.

PMID- 25764866
TI  - [The occurrence of simuliidotoxicosis in forensic-medical practice].

PMID- 25764867
TI  - [A case of untimely diagnostics of a disease in surgical practice].

PMID- 25764868
TI  - [The territorial state-governed medical expert facilities and law-enforcement
      agencies: the problems of their interaction].
AB  - This paper is concerned with the theoretical aspects and present-day practice of
      commissioning expert assessments and performance of forensic medical expertise.
      Special attention is given to the conceptual problem of the interaction between
      the organizations engaged in forensic medical examination and law-enforcement
      bodies. The authors outline the most promising directions for the improvement of
      cooperation between such agencies, preliminary investigation and criminal enquiry
      facilities.

PMID- 25764869
TI  - [On the problem of forensic medical prophylaxis].
AB  - The authors summarize the experience with the participation of forensic medical
      experts in reducing the crime rise, prophylaxis of socially significant
      pathologies (such as drug addiction, diabetes mellitus, tuberculosis, oncological
      diseases, HIV infection) and improvement of health services to the population as
      exemplified by the activities of the specialists of Sankt-Peterburg Bureau of
      Forensic Medical Expertise. The special emphasis is laid on the role of the
      city's therapeutic and prophylactic facilities in this work and up-to-date high
      tech laboratory and special investigations.

PMID- 25764870
TI  - [Forensic chemistry as a pharmaceutical discipline].
AB  - The principal objectives and problems facing forensic chemistry expertise are
      considered. In addition, its development as a pharmaceutical discipline, its
      goals and practical tasks are discussed.

PMID- 25764871
TI  - [About the work of the round table on "the legal support of healthcare services
      and legal protection of the health provider"].

PMID- 25764872
TI  - [In memory of Evel Savelevitch Baschinskiy].

PMID- 25764873
TI  - [The method of three-dimensional modeling for the reconstruction of the
      circumstances of the event taking into consideration blood stains].
AB  - The objective of the present study was to estimate the possibility of using
      computer-assisted three-dimensional modeling for the solution of selected
      problems of forensic medical expertise. This approach is illustrated by an
      example of the reconstruction of the scene of action and circumstances of the
      injury taking into consideration blood stains.

PMID- 25764874
TI  - [The role of the systemic approach in the establishment of the forensic medical
      diagnosis].
AB  - The original classification of the approaches to the establishment of the
      forensic medical diagnosis is proposed. It includes the following main
      components: 1) verification of the hypothesis; 2) the search for the specific
      symptoms of the disease or injury of interest; 3) the use of mathematical
      statistics for the selection of the most informative symptoms; 4) mathematical
      simulation and simultaneous comprehensive evaluation of the large number of signs
      and symptoms, 5) differential diagnostics; 6) the method of exclusion; 7)
      syndrome diagnostics. The comparison of these approaches based on a voluminous
      material (793 observations) has demonstrated the advantages of the latter one.
      The recommendations for its practical application are proposed.

PMID- 25764875
TI  - [The specific features of a lethal injury to the driver and the passenger of a
      scooter resulting from the collision with a car moving in the same direction].
AB  - Forensic medical diagnostics of the injuries inflicted to the drivers and the
      passengers of bicycles (scooters, mopeds, quadrocycles, etc.) remains a serious
      challenge for the specialists involved in forensic medical and combined medico
      autotechnical expertises. The present article is an overview of materials
      pertinent to the analysis of this form of traffic injuries. The approach to the
      analysis is exemplified by the case of repeated panel expertise with the purpose
      of elucidation of the mechanisms and the sequence of events leading to a combined
      blunt injury in the driver and the passenger of a scooter resulting from the
      collision with a car moving at a high speed in the same direction. Both victims
      presented with a whiplash injury to the brain stem region responsible for their
      immediate death at the scene of the accident. The results of the expertise
      allowed to differentiate between the driver and the passenger in terms of the
      extent of the injury. The authors emphasize the necessity of and good prospects
      for further traffic injury research bearing in mind a great variety of the
      aforementioned means of transportation.

PMID- 25764876
TI  - [The dermatoglyphic peculiarities of skin patterns in the subjects convicted for
      the sexual offence].
AB  - The objective of the present work was to study the dermatoglyphic peculiarities
      of skin patterns in the subjects convicted for the sexual offence and in the
      control subject who committed no criminal crime. The classical methods of
      dermatoglyphics and statistical treatment of the data obtained were employed. The
      study demonstrated abnormal dermatoglyphic features that can be used as the
      markers of the aggressive sexual behaviour.

PMID- 25764877
TI  - [Extraction of flutamide from aqueous solutions].
AB  - The objective of the present study was to elucidate peculiarities of flutamide
      extraction from aqueous solutions using he liquid-liquid extraction technique and
      spectrophotometry in the visible spectrum. The results of flutamide extraction
      were shown to depend on the chemical nature of the extractant, pH of the aqueous
      phase as well as its saturation with water and electrolytes. The study has
      demonstrated that the optimal conditions for flutamide extraction by ethylacetate
      are created by using the aqueous phase with the pH values in the range from 1.0
      to 12.0. We have calculated extraction factor necessary for the luberation of the
      desired amount of flutamide from the aqueous solutions with the use of a concrete
      solvent.

PMID- 25764878
TI  - [The scope of expert competence for the evaluation of non-compliance with the
      requirements of the departmental normative legal acts in the course of forensic
      medical panel examinations concerning "medical practice" in the criminal legal
      procedures].
AB  - This article is devoted to the analysis of the problem of expert competence for
      the evaluation of non-compliance with the requirements of the departmental
      normative legal acts in the course of forensic medical panel examinations
      concerning "medical practice" in the criminal legal procedures. The approaches to
      the solution of his problem are exemplified by forensic medical expertise of
      selected cases from obstetric and gynecological practice. It is demonstrated that
      investigations into non-compliance events arising in the work of medical
      facilities must include the analysis of the departmental normative legal acts
      that govern the organizational and diagnostic processes. These documents should
      be regarded as pertaining to an additional direct object and considered to be one
      of the constituent elements of.the offence to be identified during forensic
      medical expertise. Such documents are very specific in terms of their content and
      can not be properly interpreted by independent specialists possessing juristic
      knowledge alone. Therefore, the expert judgments concerning these issues must
      include well-reasoned arguments and solidly established evidence of normative
      legal character.

PMID- 25764879
TI  - [The analytical-synthesizing part of an expert judgment].
AB  - The present article provides the rationale for the necessity of introduction of a
      special analytical-synthesizing part in the expert judgment. It must characterize
      the process of cognitive operations in the course of forensic medical expertises
      and thereby ensure conditions for the adequate verification and assessment of the
      quality of the expertise.

PMID- 25764880
TI  - [A case of death resulting from compression of the body by the load (timber logs)
      that fell out of the vehicle in a road accident].
AB  - The authors describe an example of repeated panel forensic medical expertise of a
      case of death resulting from compression of the body by the load (timber logs)
      that fell out of the vehicle in a road accident. The mechanisms and the sequence
      of development of the injuries inflicted to a pedestrian, starting from the
      combined blunt trauma to the head, body, and extremities from the collision with
      one KamAZ lorry that was followed by the impact of the load (timber logs) that
      fell out of another KamAZ vehicle. The necessity of further investigations for
      the development of universal expert criteria for the intragroup and individual
      identification of the injurious objects is emphasized.

PMID- 25764881
TI  - [The establishment of the fact of the application of an electric circular saw
      with the high-speed reciprocating motion of the blade].
AB  - This paper reports a case of forensic medical expertise of an unintentional
      (accidental) injury inflicted by an electric circular saw with the high-speed
      reciprocating motion of the blade (jigsaw) under conditions of human operational
      activities.

PMID- 25764882
TI  - [The prospects for the application of the immunohistochemical methods for the
      establishment of intravitality and prescription of the mechanical injuries in
      forensic medical practice].
AB  - The objective of the present work was the analysis of the literature concerning
      the application of the immunohistochemical methods for the improvement of
      diagnostics of intravitality and prescription of the mechanical injuries in
      forensic medical practice. Special attention is given to the examples of
      publication dealing with the methods for addressing this issue. The most
      promising areas of the application of immunohistochemical methods are considered.
      They are exemplified by the use of specific antibodies for the establishment of
      intravitality and prescription of the mechanical injuries. The possibility of
      using the presence of fibrinogen in the pulmonary alveoli as the marker of
      prolonged strangulation is illustrated. The results of this literature review
      provided a basis for the conclusion about good prospects of the application of
      the immunohistochemical methods with the purpose of establishing intravitality
      and prescription of the mechanical injuries in forensic medical practice.

PMID- 25764883
TI  - [The problems of expert evaluation of the results of forensic chemical
      investigations of clozapine in the biological material].
AB  - The objective of the present review was to analyse the problems of expert
      evaluation of the results of forensic chemical investigations of clozapine in the
      biological material. Such an analysis is needed because many topical aspects of
      the quantitative evaluation of toxic clozapine concentrations remain unclear. The
      treatment with clozapine is associated with its accumulation in blood in
      concentrations up to 2 mg/l in the absence of any toxic effect allegedly due to
      the development of tolerability of this agent. In the tolerant patients the ratio
      of the main clozapine metabolite, norclozapine, to clozapine itself in the serum
      amounts to 0.6-0.9. This value falls down to 0.3-0.4 in case of acute
      intoxication. In the case of identification of other pharmaceutical products
      narcotic drugs together with clozapine their influence on the activity of enzymes
      responsible for clozapine biotransformation should be taken into consideration.
      The concomitant intake of clozapine and alcohol may be dangerous for the
      clozapine-intolerant subjects. It is concluded that the above observations must
      be borne in mind in the assessment of the results of forensic chemical analysis.

PMID- 25764884
TI  - [The detection of quentiapine and olanzapine in the biological objects].

PMID- 25764885
TI  - [On the applied medicolegal significance of the notion of "medical error"].
AB  - The current practice of expertise of the adequacy of organization of the
      provision of medical aid introduces a new aspect of the notion of "medical error"
      that is widely employed in medical profession, among lawyers, patients, and their
      relatives as well as in mass media. The universally accepted meaning of this
      notion has not thus far been proposed. The authors consider the medico-legal
      concept of "medical error" reconciling the contradictory opinions.

PMID- 25764886
TI  - [Auguste Ambroise Tardiue--the pre-eminent forensic medical scientist and
      children's rights advocate].
AB  - This article is devoted to the outstanding forensic medical expert whose
      activities exerted the great influence on the development of forensic medicine in
      France and all over the world. The paper present the biographical facts
      concerning A A Tardiue and characterizes the contribution he made to different
      field of forensic medicine in the middle of the XIX century including various
      forms of child abuse and neglect. A brief summary of the circumstances of some
      court trials in which A A Tardiue participated in the capacity of a forensic
      medical expert is presented in conjunction with the overview of his three most
      important written works.

PMID- 25764887
TI  - [The inter-regional scientific and practical conference with the international
      participation "The topical problems of forensic medicine and medical law"].

PMID- 25764888
TI  - [Adelaida Petrovna Zagriadskaia, the founder of the Nizhnii Novgorod School of
      Forensic Medical Experts].

PMID- 25764889
TI  - [Professors A.I. Zakonov and A.P. Zagriadskaia, the founders of the Nizhnii
      Novgorod branch of the Scientific Society of Forensic Medical Experts].

PMID- 25764890
TI  - [Research and publishing activities of professor A.P. Zagriadskaia].

PMID- 25764891
TI  - [A.P. Zagriadskaia and forensic medical experts of the Yaroslavl region].

PMID- 25764892
TI  - [The memories of the teacher].

PMID- 25764893
TI  - [The application of the methods for the measurement of tissue pressure during the
      comprehensive evaluation of the state of cadaveric tissues for the purpose of
      forensic medical expertise].
AB  - The present paper reports the results of the application of measurements of
      cadaveric tissue pressure (CTP) in forensic medical thanatology for the
      determination of the initial position of the corpse and the identification of the
      visually undetectable bleeding sites on the scalp during examination at the place
      of its discovery. Moreover, the study of the tissue pressure parameters in the
      affected tissues may be used to determine the intravitality of the injury and
      dynamics of its prescription. The parameters of intra-organ tissue pressure
      suggest its dependence not only on the prescription of the death and
      manifestations of the postmortem processes but also on the character and extent
      of the pathological process in the tissues of the organ of interest; these
      findings can be used for the verification of various diagnostic procedures
      including those for the objective elucidation of the cause of the death. It is
      concluded that the investigations along these lines extend the possibilities for
      the use of quantitative parameters of CTP for the substantiation of expert
      conclusions based on the results of forensic medical examination.

PMID- 25764894
TI  - [The role of forensic medical expertise of material evidence in the
      investigations into the cases of sexual offence].
AB  - The objective of the present study was to search for the methods for the
      enhancement of the effectiveness of forensic medical examination of material
      evidence during the investigations into the crimes against sexual immunity and
      personal sexual freedom. The work included the analysis of the relevant expert
      conclusions and copies of the decisions approving the performance of the forensic
      medical expertises. The study was carried out with the use of the following
      methods: the extraction of necessary data from the primary materials, their
      systematization and treatment by the methods of descriptive and analytical
      statistics. The study has demonstrated significant differences in the frequency
      of discovery of biological evidence of sexual offence depending on the character
      of the objects available for the examination and the time of their obtaining;
      these parameters were shown to depend on a variety of factors. It is concluded
      that the multidisciplinary approach to the selection and examination of material
      evidence for the purpose of the investigation into the cases of sexual offence
      makes it possible to considerably enhance the effectiveness of forensic medical
      expertises for the search of biological evidence of sexual crimes and thereby to
      improve the quality of this work.

PMID- 25764895
TI  - [The determination of stomach contents left on the material objects and in the
      environment].
AB  - The objective of the present experimental study was to develop the qualitatively
      new method for the determination of stomach contents left on the material objects
      and in the environment with special reference to the cases of aspiration
      asphyxia. We proposed the original approach for the determination of the origin
      of the traces of stomach contents based on the detection of pepsin, an enzyme
      that digests in the acidic milieu protein substances, such as gelatin (hydrolyzed
      collagen), a component of the emulsion layer of X-ray and photographic films.
      Samples of the stomach contents were taken from a corpse and placed on the
      surface of various materials that did not absorb moisture or repulsed it. In
      addition, materials undergoing putrefactive decomposition were investigated.
      Moreover, stains left by the cadaveric lung sections from the subjects who
      allegedly died from aspiration asphyxia on the emulsion layers were studied. A
      specially developed method was employed to detect pepsin, the main enzyme of the
      gastric juice. The majority of the studied samples including the control ones
      exhibited pepsin activity. The results of the study suggest the possibility of
      application of the proposed method for the detection of stomach contents on the
      environmental objects provided the material being studied avoided putrefactive
      modification.

PMID- 25764896
TI  - [The quantitative evaluation of the involutional changes in the kidney
      micropreparations as the method for the determination of the human biological
      age].
AB  - The objective of the present work was to study age-specific histomorphological
      changes developing in the kidneys in the course of ageing with special reference
      to the determination of the number of renal glomeruli in the field of vision
      during the microscopic examination of histological preparations. The study
      revealed the significant difference between the number of the renal glomeruli in
      the subjects under and above 50 year old. The results of the work were used to
      develop the method for the quantitative evaluation of the involutional changes in
      the kidneys for the determination of the human biological age in the combination
      with other approaches.

PMID- 25764897
TI  - [On the determination of the age of the unidentified corpses].
AB  - The objective of the present study was to determine the age of the unidentified
      corpses based on the investigation of the structure (wall width) of proximal
      epiphysis of the humeral bone. The results of analysis of the ongoing
      identification studies suggest the necessity of the development of the new
      methods for the determination of the human age including those based on the
      quantitative structural criteria for the long tubular bones. The original method
      proposed by the authors envisages the preparation of the stains from the frontal
      sawcuts of the humeral bone on the paper with the identification of the
      parameters of interest and calculation of the morphometric coefficients (MC). The
      significant differences in these coefficients suggest the possibility of using
      the proposed method for the purpose of identification expertise.

PMID- 25764898
TI  - [The study and identification of the mummified corpses in case of their mass
      discovery (a case from the expert practice)].

PMID- 25764899
TI  - [The diagnostic significance of the epidermal scales left on the material
      objects].
AB  - The objective of the present cytological study was to elucidate the possibility
      of examining epidermal scales (ES) for the purpose of forensic medical expertise
      of material evidence. It was demonstrated that epidermal scales readily removable
      and constantly detached from the skin during the process of desquamation may
      remain on the instruments of injury and other objects even after their short-term
      contact with the human body or as a result of touching these objects with the
      hands. The epidermal scales were shown to express readily detectable AB0 antigens
      which makes it possible to determine the identify of the subject to whom they
      belonged. It is concluded that cytological studies designed to detect and
      identify the source of ES may be helpful for the examination of the fingernail
      scrapings from both the victims and the suspected offenders, instruments of
      injury, cigarette stubs (especially when these objects do not exhibit the traces
      of saliva), and the condoms containing no sperm.

PMID- 25764900
TI  - [The determination of the ethanol elimination rate in the blood based on its
      concentration in the exhaled air].
AB  - The objective of the present study was to calculate the blood ethanol level from
      its content in the exhaled air. The plot of the blood ethanol level versus its
      content in the exhaled air was constructed and used to determine the rate of
      ethanol elimination from the blood. The result proved to lie within the range
      corresponding to the normal-for-age values. These data put in question the
      opinion of the independent specialist about disturbances in the alcohol
      dehydrogenase activity in blood manifested as a considerable increase of the rate
      of acetaldehyde reduction to ethanol with the decreasing ethanol dehydration
      rate. It is concluded that the prfoposed algorithm can be recommended for the
      application in the practical work of various expert services.

PMID- 25764901
TI  - [The determination of the low and medium molecular weight substances in the blood
      serum as the additional diagnostic criterion in the cases of lethal poisoning
      with narcotic drugs].
AB  - The objective of the present study was the comparative analysis of the
      concentrations of the low and medium molecular weight substances in the blood
      serum in the cases of lethal poisoning with narcotic drugs, alcoholic
      intoxication, and endogenous intoxication associated with various diseases. The
      spectrogram profile of the low and medium molecular weight substances present in
      the blood serum obtained in the case of lethal poisoning with narcotic drugs
      exhibited a peak at 260-274 nm that was not found in an analogous profile in the
      case of alcoholic intoxication or a disease. It is concluded that the proposed
      analysis can be used as an additional diagnostic criterion for the documentation
      of poisoning with narcotic drugs and/or other potent agents.

PMID- 25764902
TI  - [The medico-economic approach to the evaluation of non-violent death among the
      population of the elder age group (based on the materials of the Nizhni Novgorod
      Regional Bureau of Forensic Medical Expertise)].
AB  - The objective of the present study was the comparative analysis of the deaths
      among the elderly and senile subjects taking into consideration the growing costs
      of forensic medical expertise at the Nizhni Novgorod Regional Bureau of Forensic
      Medical Expertise.

PMID- 25764903
TI  - [The mathematical methods for the estimation of the workload on the personnel of
      the Bureau of Forensic Medical Expertise].
AB  - The objective of the present study was to analyse the financial support of
      forensic medical research with the application of mathematical methods based at
      the Nizhni Novgorod Regional Bureau of Forensic Medical Expertise. The authors
      elaborated the prognosis of the expenses for the forensic medical expertise of
      the corpses of the elderly and senile subjects.

PMID- 25764904
TI  - [Classifications in forensic medicine and their logical basis].
AB  - The objective of the present study was to characterize the main requirements for
      the correct construction of classifications used in forensic medicine, with
      special reference to the errors that occur in the relevant text-books,
      guidelines, and manuals and the ways to avoid them. This publication continues
      the series of thematic articles of the authors devoted to the logical errors in
      the expert conclusions. The preparation of further publications is underway to
      report the results of the in-depth analysis of the logical errors encountered in
      expert conclusions, text-books, guidelines, and manuals.

PMID- 25764905
TI  - [Postural asphyxia in the publications of foreign authors].
AB  - In this country, expertise of the corpses of subjects who died from various forms
      of asphixia is the third, after mechanical injury and intoxication, most frequent
      procedure in the forensic medical practice. Asphixia may be either violent (i.e.
      caused by a variety of external factors) or non-violent (resulting from the
      disturbances of intra-tissue respiration). According to the statistical data
      accumulated by the Russian State Forensic Expertise Facilities for the period
      from 2009 till 2013, the examination of the corpses of subjects who died from
      various forms of asphyxia accounts for 23.9-24.6% of all cases of violent death.
      The foreign forensic medical literature reports rare cases of death in accidents
      categorized by the authors as postural asphyxia. The objective of the present
      communication was to discuss similar observations of mechanical asphixia reported
      by the Russian forensic medical experts in the papers published in the second
      half of the 20th century in conjunction with the cases encountered in the current
      forensic medical practice. The authors emphasize that the cases of death from
      mechanical asphyxia are usually described in the domestic literature in terms of
      "compression asphyxia" or "asphyxia from compression of chest or abdomen".

PMID- 25764906
TI  - The relationship between prosthesis use, phantom pain and psychiatric symptoms in
      male traumatic limb amputees.
AB  - OBJECTIVES: The purpose of this study was to identify psychiatric symptoms by
      comparing male patients with traumatic leg amputations (LAs) with healthy
      controls and to determine the association between these psychiatric symptoms and
      phantom pain and prosthesis use characteristics. METHODS: One hundred four
      volunteers, 51 LA patients (group 1) and 53 healthy controls (group 2) were
      included. Demographic data including age, height, weight, time since amputation,
      duration of prosthesis use, and Satisfaction with Prosthesis Questionnaire scores
      were recorded. Phantom pain was measured a visual analog scale (VAS). Psychiatric
      symptoms were measured using the Symptom Checklist-90-R, Beck Depression
      Inventory, Pittsburgh Sleep Quality Index, Rosenberg Self-Esteem Scale, and State
      Trait Anxiety Inventory. Correlations were determined between time since
      amputation, duration of prosthesis use and satisfaction with prosthesis
      questionnaire scores and psychiatric scale scores. RESULTS: Amputee patients had
      higher phobic anxiety, state anxiety, trait anxiety and sleep disturbance scores
      (p<0.05) than the controls. No difference was determined in terms of psychiatric
      symptoms between the phantom pain and no phantom pain groups (p>0.05). There were
      significant negative correlations between time since amputation, duration of
      prosthesis use, duration of daily prosthesis use, and satisfaction with
      prosthesis questionnaire scores and psychiatric symptoms. CONCLUSIONS: Apart from
      anxiety (state, trait or phobic) and disturbed sleep, other psychiatric symptoms
      in amputee patients undergoing lengthy prosthetic rehabilitation may not differ
      from those of healthy controls. The presence and severity of phantom pain appear
      to be unrelated to general psychiatric symptomatology. Length of time since
      amputation, length of prosthesis use, daily length of prosthesis use and
      prosthesis satisfaction are negatively correlated with general psychiatric
      symptoms. These characteristics must be borne in mind in psychiatric and
      prosthetic rehabilitation.

PMID- 25764907
TI  - The analysis of BDNF gene polymorphism haplotypes and impulsivity in
      methamphetamine abusers.
AB  - An increasing number of evidence showed that genetic factors might contribute to
      drug abuse vulnerability. Data from genetic scans in humans suggest that brain
      derived neurotrophic factor (BDNF), a member of the neurotrophic factor family,
      may be associated with substance abuse or dependence. To test the hypothesis that
      the BDNF gene polymorphism is involved in methamphetamine abuse, we compared
      three single nucleotide polymorphisms (SNPs, rs16917204, rs16917234, and
      rs2030324) of the BDNF gene in 200 methamphetamine abusers and 219 healthy
      individuals. We also considered the association of these polymorphisms with
      impulsivity in methamphetamine abusers using Barratt Impulsivity Scale-11(BIS-11)
      Chinese version. Individual SNP analysis showed no significant differences in
      genotype and allele distributions between the methamphetamine abusers and
      controls. Haplotype analysis of rs16917204-rs16917234-rs2030324 revealed that a
      major C-C-T haplotype was significantly associated a lower odds of
      methamphetamine abuse, even after Bonferroni correction. Within the
      methamphetamine-abuse group, subjects carrying the T allele of rs2030324 genotype
      had significantly higher motor impulsivity scores of BIS compared to those with
      the C/C genotype. Our findings suggest that the BDNF gene polymorphism may
      contribute to the impulsivity in methamphetamine abusers. 

PMID- 25764908
TI  - Experiences of discrimination and the feelings of loneliness in people with
      psychotic disorders: the mediating effects of self-esteem and support seeking.
AB  - OBJECTIVE: People with psychotic disorders frequently become targets of
      discrimination, which may have devastating effects on their social relations and
      lead to the feelings of loneliness. This study has explored whether self-esteem
      and support seeking serve as mediators in the relationship between experiences of
      discrimination and loneliness. METHODS: A total of 110 persons with psychotic
      disorders (International Classification of Diseases, 10th Revision (ICD-10): F20
      F29) were evaluated with self-report measures of discrimination experiences, self
      esteem, support seeking and loneliness. The relationships between variables were
      examined with path modeling. Bootstrap mediation analyses were used for testing
      the statistical significance of indirect effects. RESULTS: Experiences of
      discrimination have been demonstrated to increase the level of loneliness both
      directly and indirectly. The indirect effect of discrimination on loneliness via
      self-esteem decrement has been proven to be significant. Support has been also
      found for a mediation model in which discrimination experiences negatively affect
      self-esteem, an undermined self-esteem diminishes the tendency to seek social
      support, and reduced support seeking worsens the sense of loneliness. However,
      discrimination experiences and support seeking have turned out to be unrelated
      and thus the hypothesized indirect effect of discrimination on loneliness through
      the weakening of the willingness to seek social support has not been confirmed by
      the data. CONCLUSIONS: The findings contribute to the understanding of the
      mechanisms through which experiences of discrimination aggravate perceived social
      isolation. Self-esteem and the tendency to seek social support have emerged as
      possible targets for interventions aiming to counteract the negative influence of
      rejection experiences on social relationships of people with psychotic disorders.

PMID- 25764909
TI  - Murine arterial thrombus induction mechanism influences subsequent
      thrombodynamics.
AB  - BACKGROUND: The mechanism of thrombotic induction in experimental models can vary
      greatly, as can the applied evaluative measures, making comparisons among models
      difficult. OBJECTIVES: This study comparatively evaluated the arterial
      thrombodynamic response among injury mechanisms. METHODS: Thrombotic responses
      were induced in mouse carotid arteries, with subsequent intravital imaging using
      rhodamine-6G-labeled platelets to quantitate platelet accumulation over
      30minutes. Nine induction methods were evaluated: brief pinch, temporary hard
      ligation, cautery/heat, needle puncture, intralumenal wire (scratch),
      intralumenal adventitia/collagen (2 different models), and brief exposures to
      either iron-based surface electrolytic injury or ferric chloride. RESULTS: The
      accumulation of platelets was variable among induction methods, with a greater
      response to more severe injury mechanisms, free radical injury, and exposed
      collagen. Temporal profiles were generated by normalizing data to peak platelet
      accumulation for each run; rapid platelet development and subsequent detachment
      were found for mechanical injuries that maintained vessel integrity (pinch and
      ligation injuries), with more sustained growth for more severe mechanical (wire)
      injury or breach of the vessel (needle puncture or intralumenal collagen). A
      delayed but extended temporal response was seen with free radical injury (both
      electrolytic and ferric chloride). CONCLUSIONS: These findings demonstrate a
      dependence of platelet thrombodynamics on the method of induction, with collagen
      exposure causing greater, more prolonged activity, while free-radical injury
      effected a delayed but sustained platelet thrombus formation with slower
      resolution. A better understanding of how these various injury models relate to
      clinical causes of arterial thrombosis is needed for optimal translational
      interpretation of murine models of thrombosis.

PMID- 25764910
TI  - The spectrum of thrombin in acute coronary syndromes.
AB  - The role of thrombin in vascular physiology and pathophysiology continues to
      impact our understanding of many cellular processes and systems including the
      function of platelets, endothelial cells, smooth muscle cells, leukocytes and the
      regulation of the coagulation cascade. Recent acute coronary syndrome clinical
      trial results that have compared the use of parenteral or oral anticoagulants
      versus or in combination with anti-platelet agents have forced a reexamination of
      the importance of thrombin activity in influencing patient outcomes, particularly
      in the area of secondary prevention. The debate of the need to include oral
      anticoagulation as a concomitant or replacement therapy to an antiplatelet
      regimen as a means to improve patient outcomes requires further examination and
      larger prospective clinical trials. 

PMID- 25764911
TI  - The use of optional inferior vena cava filters of type Optease in trauma patients
      -a single type of filter in a single Medical Center.
AB  - BACKGROUND: Venous thromboembolism (VTE) is a frequent complication of patients
      who experienced major trauma. Prevention of VTE is usually by thrombophylaxis and
      or by the use of a retrievable filter. Lately, the use of a retrievable filter in
      trauma patients has increased despite evidence cautioning against its use. AIMS:
      To evaluate complications related to a single type of filter prophylactically
      used in a tertiary trauma center and search for risk factors that may preclude
      filter retrieval METHODS: 142 patients aged 16 through 60 who experienced a major
      trauma and were treated with a prophylactic IVC filter of type optease were
      evaluated. RESULTS: The median time from trauma to filter insertion was 2days and
      low molecular weight heparin at prophylactic dose was initiated in 92% once the
      filter was inserted. Nine patients developed IVC thrombosis and one of them died
      despite the use of thrombolytic therapy. Another 8 patients developed lower
      extremities deep vein thrombosis. The filter was left in place in 13 more
      patients after attempted filter removal was unsuccessful. Among patients with
      successful removal, the median dwelling time was 30days. There was no
      relationship between successful removal and age, sex, BMI, Glasgow coma scale, or
      injury severity score of patients when first evaluated. CONCLUSIONS: Of concern
      is the persistent complications related to IVC filter even with the prophylactic
      use of anticoagulants and the dose of radiation trauma patients were exposed
      during insertion and retrieval of filter. Thus, the routine use of IVC filter in
      trauma patients may not be desirable.

PMID- 25764912
TI  - CCL8 and the Immune Control of Cytomegalovirus in Organ Transplant Recipients.
AB  - Monitoring of cytomegalovirus cell-mediated immunity is a promising tool for the
      refinement of preventative and therapeutic strategies posttransplantation.
      Typically, the interferon-gamma response to T cell stimulation is measured. We
      evaluated a broad range of cytokine and chemokines to better characterize the ex
      vivo host-response to CMV peptide stimulation. In a cohort of CMV viremic organ
      transplant recipients, chemokine expression-specifically CCL8 (AUC 0.849 95% CI
      0.721-0.978; p = 0.003) and CXCL10 (AUC 0.841, 95% CI 0.707-0.974; p = 0.004)-was
      associated with control of viral replication. In a second cohort of transplant
      recipients at high-risk for CMV, the presence of a polymorphism in the CCL8
      promoter conferred an increased risk of viral replication after discontinuation
      of antiviral prophylaxis (logrank hazard ratio 3.6; 95% CI 2.077-51.88). Using
      cell-sorting experiments, we determined that the primary cell type producing CCL8
      in response to CMV peptide stimulation was the monocyte fraction. Finally, in
      vitro experiments using standard immunosuppressive agents demonstrated a dose
      dependent reduction in CCL8 production. Chemokines appear to be important
      elements of the cell-mediated response to CMV infection posttransplant, as here
      suggested for CCL8, and translation of this knowledge may allow for the tailoring
      and improvement of preventative strategies.

PMID- 25764913
TI  - Air pollution on the agenda in India.

PMID- 25764914
TI  - Parental allergic disease before and after child birth poses similar risk for
      childhood allergies.
AB  - Whether the strength of associations between parental and child allergic diseases
      differs by whether the first onset of the parental disease is before or after a
      child's birth has never been examined and is the aim of this study. Yearly
      childhood asthma, allergic rhinitis, and eczema diagnoses were longitudinally
      regressed against the effect of a parental disease (pre- vs post-child birth) of
      the same type separately for each parent using generalized estimation equations.
      Both a maternal and paternal history of asthma were associated with childhood
      asthma prevalence up to 15 years of age. Effect estimates were similar for
      parental asthma with first onset before and after the birth of the child. The
      results for allergic rhinitis and eczema were less consistent. Parental allergic
      diseases with first onsets before and after the birth of a child both pose risks
      to childhood allergic disease in the offspring, especially for asthma.

PMID- 25764915
TI  - Communication changes following non-glottic head and neck cancer management: The
      perspectives of survivors and carers.
AB  - PURPOSE: Head and neck cancer (HNC) survivors may experience functional changes
      to their voice, speech and hearing following curative chemoradiotherapy. However,
      few studies have explored the impact of living with such changes from the
      perspective of the HNC survivor and their carer. The current study employed a
      person-centred approach to explore the lived experience of communication changes
      following chemoradiotherapy treatment for HNC from the perspective of survivors
      and carers. METHOD: Participants included 14 survivors with non-glottic HNC and
      nine carers. All participants took part in in-depth interviews where they were
      encouraged to describe their experiences of living with and adjusting to
      communication changes following treatment. Interviews were analysed as a single
      data set. RESULT: Four themes emerged including: (1) impairments in communication
      sub-systems; (2) the challenges of communicating in everyday life; (3) broad
      ranging effects of communication changes; and (4) adaptations as a result of
      communication changes. CONCLUSION: These data confirm that communication changes
      following chemoradiotherapy have potentially negative psychosocial impacts on
      both the HNC survivor and their carer. Clinicians should consider the impact of
      communication changes on the life of the HNC survivor and their carer and provide
      adequate and timely education and management to address the needs of this
      population.

PMID- 25764916
TI  - Usefulness of a pre-procedure ultrasound scanning of the lumbar spine before
      epidural injection in patients with a presumed difficult puncture: A randomized
      controlled trial.
AB  - Ultrasound (US) is widely used in rheumatology to study and guide injection of
      peripheral joints. It can also provide useful information about the anatomy of
      the lumbar spine. Studies have shown that US examination of the spine was a
      useful tool to help perform epidural anaesthesia. The purpose of the study was to
      determine if the selection of the optimum puncture level by US may facilitate
      epidural steroid injection in case of presumed difficult puncture (BMI>30
      kg/m(2), age>60 years or lumbar scoliosis). METHODS: We performed a prospective
      randomized controlled study. Eighty patients were randomized in two groups: US
      group (n=40) which underwent a pre-procedure spinal US to determine the optimal
      lumbar level for injection or control group (n=40) for which the level of
      injection was determined by palpation. Primary endpoint was the pain during the
      procedure assessed using the Visual Analogue Scale (VAS). RESULTS: We found a
      positive correlation between depth of the epidural space and BMI (P<0.001) and a
      negative correlation between size of the interspinous spaces and age (P<0.01).
      Visibility of the epidural space was not altered by obesity or age. We observed a
      trend toward a reduction in pain intensity during the procedure in the US group
      compared to the control group with a mean difference at -0.94 [-1.90; 0.02] but
      the difference was not significant (P=0.054). CONCLUSION: US of the lumbar spine
      was feasible in patients with lumbar conditions even in obese and old ones and
      allowed the visualization of the epidural space. However, pre-procedure US
      examination did not reduce pain during the procedure.

PMID- 25764918
TI  - [Go forward hand in hand to create success].

PMID- 25764917
TI  - SARS hCoV papain-like protease is a unique Lys48 linkage-specific di-distributive
      deubiquitinating enzyme.
AB  - Ubiquitin (Ub) and the Ub-like (Ubl) modifier interferon-stimulated gene 15
      (ISG15) participate in the host defence of viral infections. Viruses, including
      the severe acute respiratory syndrome human coronavirus (SARS hCoV), have co
      opted Ub-ISG15 conjugation pathways for their own advantage or have evolved
      effector proteins to counter pro-inflammatory properties of Ub-ISG15-conjugated
      host proteins. In the present study, we compare substrate specificities of the
      papain-like protease (PLpro) from the recently emerged Middle East respiratory
      syndrome (MERS) hCoV to the related protease from SARS, SARS PLpro. Through
      biochemical assays, we show that, similar to SARS PLpro, MERS PLpro is both a
      deubiquitinating (DUB) and a deISGylating enzyme. Further analysis of the
      intrinsic DUB activity of these viral proteases revealed unique differences
      between the recognition and cleavage specificities of polyUb chains. First, MERS
      PLpro shows broad linkage specificity for the cleavage of polyUb chains, whereas
      SARS PLpro prefers to cleave Lys48-linked polyUb chains. Secondly, MERS PLpro
      cleaves polyUb chains in a 'mono-distributive' manner (one Ub at a time) and SARS
      PLpro prefers to cleave Lys48-linked polyUb chains by sensing a di-Ub moiety as a
      minimal recognition element using a 'di-distributive' cleavage mechanism. The di
      distributive cleavage mechanism for SARS PLpro appears to be uncommon among USP
      (Ub-specific protease)-family DUBs, as related USP family members from humans do
      not display such a mechanism. We propose that these intrinsic enzymatic
      differences between SARS and MERS PLpro will help to identify pro-inflammatory
      substrates of these viral DUBs and can guide in the design of therapeutics to
      combat infection by coronaviruses. 

PMID- 25764919
TI  - [Etiologies and clinical features of 19 cases with bilateral acute sensorineural
      hearing loss].
AB  - OBJECTIVE: To investigate the etiologies and clinical features for bilateral
      acute sensorineural hearing loss (bi-ASNHL). METHODS: The clinical data of 19
      cases presenting with bi-ASNHL were retrospectively analyzed, including the
      clinical features, systemic examinations, laboratory examinations, audiology and
      radiology results, as well as the prognosis. RESULTS: There were 15 non-otologic
      diseases in 19 patients, accounting for 78.9% of the total cases, most of which
      were disorders with multisystem and multi-organ disorder. The central nervous
      system diseases including fungal meningitis, tuberculous meningitis, and viral
      encephalitis in 3 patients. The clinical features of deafness were bilateral,
      progressive, accompanied with fever, headache, dizziness, nausea, vomiting and
      change of mental status. There was a decrease in speech recognition score (SRS),
      and speech recognition threshold (SRT) was obviously inferior to pure tone
      average (PTA) disproportionally. Diseases of immune system including antineural
      cytoplasmic antibody (ANCA)-associated systemic vasculitis (AASV), relapsing
      polychondritis (RP), rheumatoid arthritis (RA), and systemic lupus erythematosus
      (SLE) in 5 patients. They showed the characteristics of bilateral, progressive
      and simultaneous autoimmune disease. Hematological and endocrine system diseases
      including diabetes mellitus, leukemia, and thyroid hypofunction in 5 patients.
      The deafness had the characteristics of symmetry and progressivity. Otologic
      diseases including large vestibular aqueduct syndrome (LVAS) and sudden
      sensorineural hearing loss (SSNHL) in 4 patients; Drug-induced sensorineural
      deafness happened in 2 patients. After the treatment aimed at the causes, 1 case
      was cured, 3 patients were markedly effective, 7 patients were effective, and 8
      patients were ineffective(including dead and refusal cases), with a total
      effective rate of 57.9%. CONCLUSIONS: The most of bi-ASNHL cases are often
      associated with systemic diseases. Clinicians should analyze the history and
      clinical characteristics in detail, and complete specific laboratory
      examinations, audiology and imaging examinations in order to reveal the causative
      diseases. It should be treated aimed at the etiology.

PMID- 25764920
TI  - [Clinical analysis of primary nasal sinus osteoma].
AB  - OBJECTIVE: To summarize and analyze the clinical features, diagnosis, surgical
      approaches and treatment outcomes of patients with primary nasal sinus osteoma.
      METHODS: A retrospective review of 48 cases with primary nasal sinus osteoma
      treated from January 2007 to December 2013 was performed. All patients underwent
      preoperative CT scan and postoperative histopathologic examination. The surgical
      approaches included lateral rhinotomy in 14 cases, nasal endoscopic resection in
      12 cases, coronal surgical incision craniotomy in 13 cases, combined craniofacial
      approach in 4 cases, and Caldwell-Luc approach in 5 cases. RESULTS: The
      postoperative pathological diagnosis consisted of 3 variants, including 20 for
      compact type and 15 for cancellous type, and 13 for mixed type. Six cases were
      lost to follow-up and 42 cases were followed up for 6-60 months, 5 cases
      recurred. The post-operative complications included sinus mucous cyst in 4 cases,
      cerebrospinal fluid leak in 3 cases. CONCLUSIONS: Nasal sinus osteoma are common.
      CT or MRI is helpful to evaluate the osteoma size, location and possible sources,
      and to make operation scheme. Surgery is the first choice for sinus osteoma.
      Lateral rhinotomy and nasal endoscopic resection can be applied to most sinus
      osteoma. The prognosis of sinus osteoma is good, with fewer recurrence.

PMID- 25764921
TI  - [Management of nasal orbital cellulitis in children].
AB  - OBJECTIVE: To analyze the clinical characteristics, diagnostic and treatment
      principle of orbital cellulitis in children, and to improve the experience of
      antibiotic treatment in orbital cellulites. METHODS: Twenty children were
      admitted to Shenzhen Children's Hospital with the diagnosis of nasal orbital
      cellulitis between January 2009 and December 2013. The children were severe
      enough to warrant hospital admission. There were 13(65%) males and 7 (35%)
      females. The median age was 3.5 years (2 months to 7.2 years). The relationship
      between the serum C-reactive protein (CRP), white blood cell count and the
      hospitalization days were analyzed. The children were divided into 2 groups:
      Cefoperazone Sodium and Sulbactam Sodium for injection group and other antibiotic
      treatment group, the difference was compared. Statistical calculation was
      performed using SPSS 13.0 software. RESULTS: The serum CRP [(29.8 +/- 22.0) mg/L]
      at the time of admission had a positive correlation with the time of
      hospitalization[ (6.3 +/- 4.1) d, r = 0.46, P < 0.05]. The time of CRP decreased
      to normal range after admission [(3.4 +/- 1.8) d] were apparently related to the
      hospitalization time (r = 0.81, P < 0.01). The hospital days whose CRP could be
      decreased to normal within 3 days [n = 12, (4.3 +/- 1.7) d] were significantly
      shorter than that in the others [n = 8, (9.1 +/- 5.0) d, t = 2.61, P < 0.05]. The
      hospitalization of 12 cases with Cefoperazone Sodium and Sulbactam Sodium for
      injection [(4.3 +/- 1.9) d] was shorter than that in other 8 cases with other
      drugs [(9.3 +/- 4.7) d, t = 2.83, P < 0.05]. Bacterial pathogens were only
      identified in 4 children, including 3 cases of methicillin-resistant
      staphylococcus aureus (MRSA), 1 case of streptococcus anginosus. Only 1 case in
      20 cases with positive blood culture for Staphylococcus aureus, consistented with
      the pus culture. CONCLUSIONS: If early treatment at the first three days is
      valid, the course of nasal orbital cellulitis will be shorter and the orbital
      abscess can be prevented. Cefoperazone sulbactam and Sulbactam Sodium for
      injection is effective in treating pediatric orbital cellulitis.

PMID- 25764922
TI  - [Olfactory function in patients with idiopathic Parkinson's disease].
AB  - OBJECTIVE: To analyze the correlation between olfactory bulb (OB) volume with
      depth of olfactory sulcus (OS) and olfactory function in patients with idiopathic
      Parkinson's disease (IPD). METHODS: One hundred patients with IPD between January
      2011 to December 2013 in Tianjin Huanhu Hospotal were compared with one hundred
      controls in terms of olfactory function T&T testing, OB volume and depth of OS
      assessed with Magnetic resonance imaging (MRI). One hundred IPD patients were
      investigated and estimated H-Y degrees, UPDRS, MMSE, MoCA. SPSS 13.0 software was
      used to analyze the data. RESULTS: T&T olfactory testing revealed that IPD
      patients (3.0 +/- 0.3) had higher scores than controls (1.3 +/- 0.2, t = 2.537, P
      < 0.01). Both men and women with IPD were affected by the same extent of
      olfactory loss (t = 0.893, P > 0.05). Both men and women as controls were
      affected by the same extent of olfactory loss(t = 1.184, P > 0.05). OB volume of
      left side in IPD patients was (34.25 +/- 5.14) mm(3), right side was (35.79 +/-
      5.28)mm(3), average OB volume was (35.28 +/- 5.21) mm(3); OB volume of left side
      in controls was (47.38 +/- 6.47) mm(3), right side was (47.75 +/- 6.51) mm(3),
      average OB volume was (47.53 +/- 6.49) mm(3); OB volume were lower in IPD
      patients as compared to controls (t value were 2.876, 2.747, 2.798, all P <
      0.01). OS depth study revealed no statistical difference between IPD patients and
      controls (t value were 0.914, 0.987, 0.951, all P > 0.05). Olfactory discriminate
      threshold was negatively correlated with average OB volume in IPD patients and
      controls (r value were -0.537,-0.526, both P < 0.05); was no correlated with
      average depth of OS (r value were -0.142, -0.157, both P > 0.05). There was
      relation between the average OB volume and UPDRS III, UPDRS, the degree of H-Y in
      IPD patients (r value were 0.312, -0.419, -0.358, all P < 0.05). However the
      average OB volume was not related to the course of disease (r = -0.089, P >
      0.05). CONCLUSIONS: The OB volume is lower in IPD patients as compared to
      controls, the depth of OS have no significant changes in IPD patients; The OB
      volume is correlated with olfactory function, the depth of OS is not correlated
      with olfactory function; Olfactory function lower degree is accordance with
      serious degree in IPD patients, is not accordance with the course of disease.

PMID- 25764923
TI  - [Clinical analysis of 24 cases of carotid body tumor].
AB  - OBJECTIVE: To study the clinical diagnosis and preoperative management of carotid
      body tumor. METHODS: A total of 24 cases with carotid body tumors underwent
      surgery from 2003 to 2013 were reviewed. The clinical and imaging features,
      treatment and prognosis were retrospectively evaluated. Five of the 24 patients
      were males and 19 were females. Twenty-three cases were benign and one case was
      malignant. Seven of the 24 patients had bilateral tumors. RESULTS: Nineteen of
      twenty-four patients underwent digital subtraction angiography (DSA) and
      temporary balloon occlusion (TBO) test, and one case of them was positive in the
      test. Twenty-three benign case were treated with operation. The malignant one
      treat with biopsy. Three cases underwent resection of tumors with both the
      internal and external carotid arteries without carotid reconstruction, and none
      of the three patients died or presented with hemiplegia after operation. Twenty
      three benign cases were followed up for 6-122 months, the median was 75 months.
      The malignant patient died 6 months after operation. CONCLUSION: TBO and DSA are
      reliable and practical methods to determine the safety of carotid ligation and
      can be used as routine preoperative examinations.

PMID- 25764924
TI  - [Preliminary report on meticulous operation of thyroid lobectomy].
AB  - OBJECTIVE: Thyroid lobectomy can be programmed to operate as "step by step". Each
      step must be performed meticulously with quality control, so as to minimize the
      complications of surgery. METHODS: From May 2013 to Auguest 2014, the meticulous
      thyroid operation was conducted in 72 cases (144 lobectomies). Pre- and post
      operative evaluations by strobe laryngoscopy, parathyroid hormone (PTH), and
      blood calcium examinations were conducted in all cases. RESULTS: Four cases
      (5.6%) had transient recurrent laryngeal nerve paralysis after surgery, but no
      permanent recurrent laryngeal nerve paralysis. There was no transient or
      permanent superior laryngeal nerve paralysis. Transient hypoparathyroidism
      occurred in 10 cases, with no permanent hypoparathyroidism. No case presented
      with postoperative bleeding or infection. CONCLUSIONS: "Meticulous operation of
      thyroid lobectomy" may minimize effectively the complication of surgery.

PMID- 25764925
TI  - [Dynamic observation on the short-term change of xerostomia after intensity
      modulated radiotherapy for patients with nasopharyngeal carcinoma].
AB  - OBJECTIVE: To dynamically analyze the change of xerostomia in patients with
      nasopharyngeal carcinoma after radiotherapy by DW MRI. METHODS: Twenty-three
      nasopharyngeal carcinoma patients confirmed by pathology were enrolled.
      Male/Female: 19/4. The age was from 37 to 69 years. The patients were divided
      into two groups: G1, Dmean<26 Gy, G2, Dmean >= 26 Gy. All patients underwent
      salivary glands examination by DW MRI before IMRT, at the end of IMRT, 6 months
      and 12 months after IMRT, at the same time the ADC value of salivary glands were
      calculated. According to the RTOG/EORTC salivary gland injury grading standard
      and referring the subjective index, the degree of xerostomia was assessed. SPSS
      13.0 and SAS 8.2 software were used to analyze the data. RESULTS: At the end of
      IMRT, the change tendency of ADC in parotid and submandibular glands value was
      different in patients with different degree of xerostomia (F = 11.52, P < 0.01).
      At the end of IMRT, a significant difference for degree of xerostomia could be
      found in patients within different irradiation dose groups (Z = -3.622, P <
      0.01). Clinical stage, treatment mode and age had no significant effect on the
      degree of xerostomia for patients at the end of IMRT (Z value was -0.791, -0.949,
      2.488, all P > 0.05). A significant difference of xerostomia degree in patients
      was found at the various follow-up time after IMRT (chi(2) = 19.59, P < 0.01).
      CONCLUSIONS: There is good correlation between the function of salivary gland and
      subjective rating of xerostomia in patients with nasopharyngeal carcinoma after
      radiotherapy. The degrees of salivary gland function and dry mouth in patients
      with nasopharyngeal carcinoma damage evaluate with illuminated dose increases.
      The function of salivary gland gradually restored and the degree of dry mouth
      gradually reduce with the extension of time after radiotherapy.

PMID- 25764926
TI  - [Low expression of succinate dehydrogenase subunit B in locally recurrent
      nasopharyngeal carcinoma and implication for prognosis].
AB  - OBJECTIVE: To study the expression of succinate dehydrogenase subunit B (SDHB) in
      the tissues of locally recurrent nasopharyngeal carcinoma (rNPC) and the
      correlation with the clinicopathological factors and prognosis of rNPC. METHODS:
      Immunohistochemistry was used to detect the expression of SDHB in the tissues of
      primary and locally recurrent nasopharyngeal carcinoma. The relationship between
      SDHB expression and clinicopathological features was analyzed using the Chi
      square test, and Kaplan-Meier method and Log-rank test were used for survival
      analysis. The independent prognostic factors of rNPC were analyzed by Cox
      regression model. RESULTS: Low SDHB expression was showed in 76.5% (39/51) of the
      patients with rNPC, significantly higher than 57.1% (24/42) of primary
      nasopharyngeal carcinoma (chi(2) = 4.098, P < 0.05). Low expression of SDHB
      strongly was correlated with T classification, clinical stage and cranial nerve
      palsy. Patients with low SDHB expression had a shorter survival time and a lower
      3 or 5 year survival rate compared to the patients with high SDHB expression.
      Multivariate analysis showed that low SDHB expression was an independent
      predictor for overall survival of patients with rNPC (P < 0.05). CONCLUSION: The
      low SDHB expression is an independent indicator for poor prognosis of rNPC and
      may play an important role in the recurrence of rNPC.

PMID- 25764927
TI  - [ATP release mechanism from the supporting cells in the Kolliker organ in vitro
      in the cochlea of newborn rat].
AB  - OBJECTIVE: The specific mechanism underlying in the Adenosine triphosphate (ATP)
      release from the Kolliker's organ is still unknown. The present study was
      designed to investigate whether the supporting cells in the Kolliker organ in
      vitro release ATP and to explore the mechanism of ATP releasing from these cells.
      METHODS: Supporting cells in the Kolliker organ from P1 rats were isolated,
      purified and cultured with a combinatorial approach of enzymatic digestion and
      mechanical separation. Quinacrine staining was used to observe the cochlear
      membranous labyrinth and supporting cells. the bioluminescence assay was chosen
      to explore the release ATP from supporting cells in the Kolliker organ, when the
      ATP metabolism of the cells was influenced, the intracellular or extracellular
      Ca(2)+ concentration changed, the hemichannels blocked, and the phospholipase
      signaling pathways inhibited. RESULTS: There were intensely numerous star-like
      green spots of quinacrine staining in the cytoplasm of supporting cells. There
      was a strong log-linear relationship in the ATP standard curve generated by the
      bioluminescence assay. With increasing concentrations of bafilomycin A1, the ATP
      concentration in the culture medium of the supporting cells in the Kolliker organ
      decreased, while with adipic acid didecyl, it increased. In a certain
      concentration range, with increasing extracellular Ca(2)+ concentration, the
      supporting cells in the Kolliker organ releasing ATP decreased, while the
      intracellular Ca(2)+ concentration increased, the results showed the elevation of
      the amount of ATP release. Adding chelerythrine chloride or aristolochid acid
      into the culture medium of the supporting cells in the Kolliker organ could
      decrease the ATP release significantly via inhibiting the hemichannels. In
      addition, by reducing intracellular Ca(2)+ concentration, inhibition of
      intracellular signaling pathways phospholipase also decreased ATP release.
      CONCLUSIONS: This study demonstrated the presence and release of ATP from the
      supporting cells cultured in vitro. It showed that the changes of the
      intracellular and extracellular Ca(2)+ concentration could affect on the ATP
      release from the supporting cells in the Kolliker organ by regulating the
      hemichannels openings.

PMID- 25764928
TI  - [A national investigation on the application of Chinese guideline for the
      diagnosis and treatment of chronic rhinosinusitis].
AB  - OBJECTIVE: To investigate the application of Chinese guideline for the diagnosis
      and treatment of chronic rhinosinusitis (2008, Nanchang) on a national scale.
      METHODS: The contents of the guideline and its relevant applied indicators were
      designed into an initial questionnaire and, after a pre-survey, revised into a
      formal questionnaire. Then a stratified sampling was selected out of
      otolaryngology practitioners in the different level hospitals across the country.
      After a uniform training, the investigators were sent to these different
      hospitals to conduct questionnaire survey by face to face interview with
      otolaryngology respondents. Based on the summarized data, statistical analyses on
      the awareness and practice status of the guideline, together with their
      influencing factors, were made. SPSS 16.0 software was used to analyze the data.
      RESULTS: Issuing and withdrawing questionnaires were performed from December 2012
      to June 2013 and 1 240 respondents in 350 hospitals from 30 different provinces,
      municipalities or autonomous regions were effectively investigated. An average
      awareness and practice rate of 48.7% and 40.8% upon the guideline was acquired,
      respectively. There was a significant correlation (r = 0.280, P = 0.000) between
      the two indicators. With linear regression, county-level hospitals, junior
      practitioners, non-rhino professionals were the risk factors of poor guideline
      adherence. In addition, respondents form western region showed lower awareness
      and practice rate than that of ones from central and eastern region. CONCLUSION:
      The adherence on Chinese guideline for the diagnosis and treatment of chronic
      rhinosinusitis is nationally low, so popularization of activities should be
      urgently strengthened, especially in focus areas, focus hospitals, and focus
      groups.

PMID- 25764929
TI  - [Perioperative management of bilateral bronchial foreign bodies in infants].
AB  - OBJECTIVE: To explore the perioperative management of bilateral bronchial foreign
      bodies in infants to improve the cure rate in the children. METHODS: The medical
      charts of 45 infants with bilateral bronchial foreign bodies were reviewed.
      Clinical features and key points to surgery as well as post-operative care were
      analyzed. RESULTS: All foreign bodies were removed with rigid bronchoscopy under
      general anesthesia, and 44 of 45 infants were cured with assistance of anti
      infective treatments within 3-5 days and one with acute laryngitis and bronchitis
      was cured through 10-day anti-infective treatment with vancomycin. CONCLUSION:
      Removal of foreign body by rigid bronchoscopy under general anesthesia is a
      preferred method to treat bilateral bronchial foreign bodies in infants, to whom
      early diagnosis, early treatment and postoperative careful care are keys to get a
      good outcome.

PMID- 25764930
TI  - [Analysis on influencing factor of the complications of percutaneous dilational
      tracheotomy].
AB  - OBJECTIVE: To Analyze the influence factors on the complications of percutaneous
      dilational tracheotomy. METHODS: Between August 2008 and February 2014, there
      were 3 450 patients with the indications of tracheotomy accepted percutaneous
      dilational tracheostomy, mainly using percutaneous dilational and percutaneous
      guide wire forceps in these cases. Statistical analysis was performed by SPSS
      19.0 software on postoperative complications, the possible influence factors
      including age, gender, etiology, preoperative hypoxia, obesity, preoperative
      pulmonary infection, state of consciousness, operation method, operation doctor
      and whether with tracheal intubation. RESULTS: Among 3 450 patients, there were
      164 cases with intraoperative or postoperative complications, including
      postoperative bleeding in 74 cases (2.14%), subcutaneous emphysema in 54 cases
      (1.57%), wound infection in 16 cases (0.46%), pneumothorax in 6 cases (0.17%),
      mediastinal emphysema in 5 cases (0.14%), operation failed and change to
      conventional incision in 4 cases (0.12%), tracheoesophageal fistula in 2 cases
      (0.06%), death in 3 cases(0.09%).Obesity, etiology, preoperative hypoxia,
      preoperative pulmonary infection, state of consciousness and operation method
      were the main influence factors, with significant statistical difference (chi(2)
      value was 0.010, 0.000, 0.002, 0.000, 0.000, 0.000, all P < 0.05). Gender, age,
      operation doctor and whether there was the endotracheal intubation were not the
      main influence factors. There was no significant statistical difference (P >
      0.05). CONCLUSION: Although percutaneous dilational tracheostomy is safe, but the
      complications can also happen. In order to reduce the complications, it is need
      to pay attention to the factors of obesity, etiology, preoperative hypoxia,
      preoperative pulmonary infection, state of consciousness and operation method.

PMID- 25764931
TI  - [Semicircular canal occlusion for intractable secondary otolith disease].

PMID- 25764932
TI  - [Percutaneous endovascular interventional treatment for vertebral artery
      injuries: a case report].

PMID- 25764933
TI  - [The nasal cavity and pharynx cerebral penetrating wound: clinical analysis of 3
      cases].

PMID- 25764934
TI  - [Hoarse voice as the first symptom of the thyroglossal cyst: a case report].

PMID- 25764935
TI  - [Endoscopic surgery of ypterygopalatine fossa allotriodontia].

PMID- 25764936
TI  - [Clinical investigation in one patient with multiple acyl-CoA dehydrogenase
      deficiency and hearing loss].

PMID- 25764937
TI  - [A case report: myofibroblastic sarcoma of the nasal cavity and skull base have
      survived 9 years after endoscopic surgery].

PMID- 25764938
TI  - [Mechanism of bone marrow mesenchymal stem cells in treatment of noise induced
      hearing loss with intravenous transplantation].

PMID- 25764939
TI  - [Electrical stimulation for treating obstructive sleep apnea hypopnea syndrome: a
      review].

PMID- 25764940
TI  - [The research situation and application prospect that 3 d printing technology in
      the field of otolaryngology department].

PMID- 25764941
TI  - Identification of a candidate therapeutic antibody for treatment of canine B-cell
      lymphoma.
AB  - B-cell lymphoma is one of the most frequently observed non-cutaneous neoplasms in
      dogs. For both human and canine BCL, the standard of care treatment typically
      involves a combination chemotherapy, e.g. "CHOP" therapy. Treatment for human
      lymphoma greatly benefited from the addition of anti-CD20 targeted biological
      therapeutics to these chemotherapy protocols; this type of therapeutic has not
      been available to the veterinary oncologist. Here, we describe the generation and
      characterization of a rituximab-like anti-CD20 antibody intended as a candidate
      treatment for canine B-cell lymphoma. A panel of anti-canine CD20 monoclonal
      antibodies was generated using a mouse hybridoma approach. Mouse monoclonal
      antibody 1E4 was selected for construction of a canine chimeric molecule based on
      its rank ordering in a flow cytometry-based affinity assay. 1E4 binds to
      approximately the same location in the extracellular domain of CD20 as rituximab,
      and 1E4-based chimeric antibodies co-stain canine B cells in flow cytometric
      analysis of canine leukocytes using an anti-canine CD21 antibody. We show that
      two of the four reported canine IgG subclasses (cIgGB and cIgGC) can bind to
      canine CD16a, a receptor involved in antibody-dependent cellular cytotoxicity
      (ADCC). Chimeric monoclonal antibodies were assembled using canine heavy chain
      constant regions that incorporated the appropriate effector function along with
      the mouse monoclonal 1E4 anti-canine CD20 variable regions, and expressed in CHO
      cells. We observed that 1E4-cIgGB and 1E4-cIgGC significantly deplete B-cell
      levels in healthy beagle dogs. The in vivo half-life of 1E4-cIgGB in a healthy
      dog was ~14 days. The antibody 1E4-cIgGB has been selected for further testing
      and development as an agent for the treatment of canine B-cell lymphoma. 

PMID- 25764942
TI  - In ovo delivery of Toll-like receptor 2 ligand, lipoteichoic acid induces pro
      inflammatory mediators reducing post-hatch infectious laryngotracheitis virus
      infection.
AB  - Toll-like receptor (TLR) ligands are pathogen associated molecular patterns
      (PAMPs) recognized by the TLRs resulting in induction of host innate immune
      responses. One of the PAMPs that binds to TLR2 and cluster of differentiation
      (CD) 14 is lipotechoic acid (LTA), which activates downstream signals culminating
      in the release of pro-inflammatory cytokines. In this study, we investigated
      whether in ovo LTA delivery leads to the induction of antiviral responses against
      post-hatch infectious laryngotracheitis virus (ILTV) infection. We first
      delivered the LTA into embryo day (ED)18 eggs via in ovo route so that the
      compound is available at the respiratory mucosa. Then the LTA treated and control
      ED18 eggs were allowed to hatch and the hatched chicken was infected with ILTV
      intratracheally on the day of hatch. We found that in ovo delivered LTA reduces
      ILTV infection post-hatch. We also found that in ovo delivery of LTA
      significantly increases mRNA expression of pro-inflammatory mediators in pre
      hatch embryo lungs as well as mononuclear cell infiltration, predominantly
      macrophages, in lung of post-hatch chickens. Altogether, the data suggest that in
      ovo delivered LTA could be used to reduce ILTV infection in newly hatched
      chickens. 

PMID- 25764943
TI  - Maternal Underestimation of Child's Weight Status and Health Behaviors as Risk
      Factors for Overweight in Children.
AB  - OBJECTIVES: To evaluate children's risk of being overweight associated with
      maternal underestimation of weight status and health behaviors. RESULTS: One
      hundred forty mother-child dyads were included. Children whose weight status was
      underestimated by their mothers were at greater risks of being overweight
      compared to those whose weigh status was correctly perceived (adjusted OR 2.31,
      95% CI 1.11-4.81). Less television viewing time was associated with a 63% reduced
      risk of being overweight (adjusted OR .37, 95% CI .17-.83). CONCLUSIONS: Maternal
      underestimation of weight status was common among overweight and normal-weight
      children, and it was associated with an increased children's risk of being
      overweight.

PMID- 25764944
TI  - Iron homeostasis and progression to pulmonary tuberculosis disease among
      household contacts.
AB  - Early identification of individuals at risk for progressing to active
      tuberculosis (TB) disease may limit new transmission and improve clinical
      outcomes. Evidence indicates altered iron homeostasis may identify those at
      greater risk of disease progression in HIV co-infection. We aimed to investigate
      iron homeostasis biomarkers as risk factors for progression to TB. Archived
      plasma samples were analyzed from household contacts of pulmonary TB index cases
      in The Gambia. Contacts were classified as asymptomatic non-progressors (n = 17)
      or TB-progressors (n = 10), which included two HIV-infected participants. Iron
      homeostasis (hemoglobin, ferritin, hepcidin, soluble transferrin receptor,
      transferrin) was assessed in all contacts at study recruitment. Plasma was
      collected a median of 910 days prior to TB diagnosis. Low transferrin around the
      time of known exposure to infectious TB was a disease progression risk factor
      among all TB-progressors (Poisson incidence rate ratio: 0.55; 95% CI: 0.35-0.89).
      Iron homeostasis also differed between early and delayed TB-progressors, with
      higher ferritin and hepcidin concentrations observed among early TB-progressors
      (mean ferritin 50.2 vs. 26.2 ng/ml; P = 0.027; mean hepcidin 37.7 vs. 5.6 ng/ml;
      P = 0.036). Iron homeostasis is associated with progression to TB among household
      contacts. Further studies are needed to elucidate mechanisms and determine the
      clinical utility of monitoring iron homeostasis biomarkers.

PMID- 25764945
TI  - [Reply to "The Low Temperature Steam and Formaldehyde (LTSF) sterilization
      system"].

PMID- 25764946
TI  - [Fluctuating nodules on the scalp of a child].

PMID- 25764947
TI  - [Acute conjunctivitis caused by respiratory Syncytial virus A group].

PMID- 25764949
TI  - Scrofuloderma: 30 years of experience from eastern Turkey.

PMID- 25764951
TI  - Biomechanics of PUs in paediatric care settings.

PMID- 25764950
TI  - An analysis of first-time blood donors return behaviour using regression models.
AB  - BACKGROUND AND OBJECTIVES: Blood products have a vital role in saving many
      patients' lives. The aim of this study was to analyse blood donor return
      behaviour. MATERIALS AND METHODS: Using a cross-sectional follow-up design of 5
      year duration, 864 first-time donors who had donated blood were selected using a
      systematic sampling. The behaviours of donors via three response variables,
      return to donation, frequency of return to donation and the time interval between
      donations, were analysed based on logistic regression, negative binomial
      regression and Cox's shared frailty model for recurrent events respectively.
      RESULTS: Successful return to donation rated at 49.1% and the deferral rate was
      13.3%. There was a significant reverse relationship between the frequency of
      return to donation and the time interval between donations. Sex, body weight and
      job had an effect on return to donation; weight and frequency of donation during
      the first year had a direct effect on the total frequency of donations. Age,
      weight and job had a significant effect on the time intervals between donations.
      CONCLUSION: Aging decreases the chances of return to donation and increases the
      time interval between donations. Body weight affects the three response
      variables, i.e. the higher the weight, the more the chances of return to donation
      and the shorter the time interval between donations. There is a positive
      correlation between the frequency of donations in the first year and the total
      number of return to donations. Also, the shorter the time interval between
      donations is, the higher the frequency of donations.

PMID- 25764952
TI  - Clinical audit of a lymphoedema bandaging system: a foam roll and cohesive short
      stretch bandages.
AB  - OBJECTIVE: Late-stage lymphoedema is characterised by chronic swelling, shape
      distortion, inflammatory processes and tissue fibrosis. Our aim was to perform a
      clinical audit of a lymphoedema compression bandaging system (Rosidal Soft foam
      roll layer and figure-of-eight application of Actico cohesive inelastic bandages)
      specifically designed for patients with late stage lower limb lymphoedema.
      METHOD: The audit explored suitability of the bandaging system, benchmarking limb
      volume changes with research evidence, and reporting patient and practitioner
      evaluations. RESULTS: A mean reduction (33%) in excess limb volume was reported
      for the 11 patients with unilateral lymphoedema who completed a course of
      bandaging over 12 days. Mean percentage reduction of absolute limb volume after
      treatment was 8%. Patient and practitioner evaluations indicated the suitability
      of this bandage system for patients with late stage lymphoedema in terms of
      comfort and effectiveness. CONCLUSION: The bandaging system is suitable for
      patients with late stage chronic swelling. Two parameters for calculating change
      in limb volume are not interchangeable. Future evaluation of the bandaging
      system, using validated outcome measures within a comprehensive research study is
      required. DECLARATION OF INTEREST: Activa Healthcare provided financial support
      to the project and supplied the materials.

PMID- 25764948
TI  - The apicomplexan glideosome and adhesins - Structures and function.
AB  - The apicomplexan family of pathogens, which includes Plasmodium spp. and
      Toxoplasma gondii, are primarily obligate intracellular parasites and invade
      multiple cell types. These parasites express extracellular membrane protein
      receptors, adhesins, to form specific pathogen-host cell interaction complexes.
      Various adhesins are used to invade a variety of cell types. The receptors are
      linked to an actomyosin motor, which is part of a complex comprised of many
      proteins known as the invasion machinery or glideosome. To date, reviews on
      invasion have focused primarily on the molecular pathways and signals of
      invasion, with little or no structural information presented. Over 75 structures
      of parasite receptors and glideosome proteins have been deposited with the
      Protein Data Bank. These structures include adhesins, motor proteins, bridging
      proteins, inner membrane complex and cytoskeletal proteins, as well as co-crystal
      structures with peptides and antibodies. These structures provide information
      regarding key interactions necessary for target receptor engagement, machinery
      complex formation, how force is transmitted, and the basis of inhibitory
      antibodies. Additionally, these structures can provide starting points for the
      development of antibodies and inhibitory molecules targeting protein-protein
      interactions, with the aim to inhibit invasion. This review provides an overview
      of the parasite adhesin protein families, the glideosome components, glideosome
      architecture, and discuss recent work regarding alternative models. 

PMID- 25764953
TI  - Safety and efficacy of active Leptospermum honey in neonatal and paediatric wound
      debridement.
AB  - OBJECTIVE: Safety is a critically important factor in the selection of products
      used in neonatal and paediatric wound care. Given the lack of standardisation of
      neonatal and paediatric wound care protocols, the goal of this study was to
      present data on the safety and efficacy of active Leptospermum honey (ALH) in
      this patient population. METHOD: A multicentre, retrospective chart review was
      conducted at eight inpatient facilities and one outpatient clinic between October
      2011 and March 2014. The number of applications of ALH, adverse events, and the
      success of debridement and wound healing were recorded. RESULTS: Data were
      collected on 115 neonatal and paediatric patients, with 121 wounds requiring
      debridement, treated with ALH. Patients were treated for an average of 18.7 days.
      ALH was well tolerated, with two (1.7%) patients reporting adverse events
      involving a transient stinging sensation on application, which did not prohibit
      additional applications of ALH. Successful debridement was achieved in 86.0% (104
      wounds), and 77.7% (94 wounds) were successfully closed using nonsurgical
      intervention. Outcomes in neonates were similar to the overall paediatric
      population, with 86.1% (31/36) wounds successfully debrided with no adverse
      events. In a subset of six patients with available pre- and post-treatment data,
      no clinically meaningful changes in white blood cell counts or glucose levels
      were associated with the initiation of treatment with ALH. CONCLUSION: The
      results of this study support ALH as a safe and effective treatment option in
      this group of patients. DECLARATION OF INTEREST: This study was supported by a
      grant from Derma Sciences (Princeton, NJ USA). Dr Amaya is a paid speaker for
      Derma Sciences.

PMID- 25764954
TI  - Dehydrated human amnion/chorion tissue in difficult-to-heal DFUs: a case series.
AB  - Diabetic foot ulcers (DFUs) occur as a result of multifactorial complications and
      are commonly found in the diabetic community. Underlying disease states such as
      neuropathy and peripheral vascular disease can slow healing rates, potentially
      leading to recurrence, amputation, and increased mortality. As with many other
      disease processes, DFUs have several treatment options, such as debriding agents,
      alginate seaweed extract, hydrocolloid gels, and amniotic membrane allografts.
      The presented cases all used a dehydrated human amniotic/chorionic membrane
      allograft (dHACM; EpiFix) to aid the healing process. Human amniotic epithelial
      membranes have seen increased usage due to their ability to enhance the healing
      process and accelerate cellular regeneration. The DFUs healed in all of the five
      patients treated, and patients saw a full recovery in 2.5-11 weeks. In addition,
      the healing time decreased in spite of the non-adherence seen in three of the
      patients. These results suggest another possible use for dHACM; however, further
      studies are required to confirm these data. DECLARATION OF INTEREST: This project
      was self-funded and had no influences outside the fact that Dr Penny is a speaker
      for MiMedx.

PMID- 25764955
TI  - Thermographic mapping of the abdomen in healthy subjects and patients after
      enterostoma.
AB  - OBJECTIVE: Heat is a sign and symptom of surgical wound infection in wound
      assessment criteria but there is currently no diagnostic tool being used in
      clinical practice to assess the skin temperature of surgical wounds. Using
      thermal imaging, the objective of this study was to map the temperature of the
      healing surgical wound and to provide confirmatory data of: a) optimum IR imaging
      distance from skin temperature target field of view (FOV) b) body composition
      effects on abdominal skin surface temperature readings c) thermal mapping
      characteristics of infected versus non-infected wounds post stoma-closure.
      METHOD: The abdominal skin surface temperature of healthy, afebrile subjects was
      measured under controlled, ambient conditions in a small (240cm x 320cm) clinical
      room. Subject standing positions were 30cm, 60cm and 100cm from the IR camera.
      Abdominal skin surface temperature and thermal imaging maps were acquired in a
      population of surgical patients before and after closure of enterostoma. RESULTS:
      Subjects (30) aged 19-52 (median=29) years were recruited. At a distance of
      100cm, each of nine anatomical regions showed a decrease in mean temperature as
      BMI increased. Subjects with BMI >25 had lower mean abdominal temperatures.
      Statistically significant differences were observed for right hypochondrium
      (p=0.022), left lumbar region (p=0.009), right lumbar region (p=0.010) and the
      umbilical region (p=0.021). Half of patients (5/10) developed surgical wound
      infection. CONCLUSION: Within the operating distances investigated, no
      significant effect on abdominal temperature readings was observed. With
      increasing BMI, lower abdominal temperatures were noted. The thermal pattern of
      abdominal surgical wounds reveals some differences between the healing and
      infected wound. Healing wounds showed changes in the thermal 'map'; an increase
      in temperature on the first post-operative day, and 'warming' over the subsequent
      five days. 'Cold spots' emerged on the thermogram of the surgical wounds which
      subsequently were shown to be infected. Within the setting of a clinical
      environment, distances up to 100cm did not significantly alter skin temperature
      readings within the FOV. There is a suggestion that body composition influences
      skin temperature. Infected surgical wounds appear 'colder' than healing wounds.
      DECLARATION OF INTEREST: The authors have no conflict or interest. The work was
      supported by a grant from the SingHealth Foundation.

PMID- 25764957
TI  - Human acellular dermal wound matrix for treatment of DFU: literature review and
      analysis.
AB  - Diabetic foot ulcers (DFUs) affect a significant number of people and the
      treatment is challenging and costly. Since only a small portion of patients
      respond to standard care, the majority require more advanced wound healing
      interventions. Human acellular dermal matrices-regenerative tissue matrices
      derived from human tissue and processed from screened donated skin-can aid wound
      closure by restoring the missing physiological factors to the microenvironment. A
      literature review of the clinical literature was performed to estimate the
      comparative effectiveness of one specific human acellular dermal wound matrix
      (HADWM; Graftjacket regenerative tissue matrix) versus standard care in healing
      DFUs. Outcomes from three prospective, controlled clinical trials, which included
      154 patients with DFUs, were pooled. A comparative analysis revealed a
      statistically significant reduction in mean wound healing time, 1.7 weeks, as
      well as a nearly four-fold improvement in the chance of healing ulcers treated
      with HADWM versus moist wound-care. These pooled results suggest that HADWM may
      improve healing outcomes for these difficult-to-heal lower extremity wounds.
      DECLARATION OF INTEREST: Alexander Reyzelman is a consultant for KCI, an Acelity
      company.

PMID- 25764956
TI  - Comparative study of two antimicrobial dressings in infected leg ulcers: a pilot
      study.
AB  - OBJECTIVE: The aim of the study was to compare the efficacy of a microorganism
      binding (MB) dressing with a silver-containing hydrofiber (SCH) dressing in
      controlling the bacterial loads of heavily colonised or locally infected chronic
      venous leg ulcers, before surgical management with homologous skin grafts.
      METHOD: A randomised comparative single centre study recruited patients
      presenting with hard-to-heal critically colonised or locally infected leg ulcers,
      who could be treated with skin grafting. Inclusion criteria included; ulcers of
      vascular aetiology, over 18 years old, a wound duration >=6 months and ankle
      brachial index (ABPI) >0.6. Patients were randomly assigned to treatment with SCH
      dressings (Aquacel Ag) or MB dressing (Cutimed Sorbact). Dressings were changed
      daily over a four-day observation period, after which they were taken for a skin
      grafting procedure. Swab samples from ulcer beds were taken in order to quantify
      the bacterial load at inclusion (D0) and at the end of the observation period day
      4 (D4). No antibiotics were administered before or during the evaluation period.
      RESULTS: Both groups (n=20 SCH, n=20 MB) were similar in gender, age,
      pathophysiology (both had 15 patients with venous leg ulcers and 5 with arterial
      leg ulcers), ulcer surface, ulcer duration, treatment-related pain and initial
      bacterial load. Analysing bacterial load variation showed a significant reduction
      of bacterial burden at D4 in both groups. In the SCH group, we found an average
      bacterial load reduction of 41.6%, with an average reduction of 73.1% in the MB
      group (p< 0.00001). No serious adverse events were reported. CONCLUSION: Our
      evaluation confirmed that MB and SCH dressings are effective in reducing the
      bacterial burden in critically colonised or locally infected chronic leg ulcers,
      without inducing adverse events, with MB dressings significantly more effective.
      DECLARATION OF INTEREST: There were no external sources of funding for this
      study. The authors have no conflicts of interest to declare.

PMID- 25764958
TI  - Comparison of lipidocolloid and chlorhexidine-impregnated tulle gras dressings
      following microscopically controlled surgery.
AB  - OBJECTIVE: Modified microscopically controlled surgery (MCS) is a staged and
      margin-controlled excision; after MCS, the selection of an appropriate initial
      wound dressing plays an important role in wound healing. A wide range of
      dressings is available for temporary wound coverage; however, data comparing
      different types of wound dressings after MCS are lacking. The aim of this study
      was to compare two commonly used and commercially available types of wound
      dressings. METHOD: We assessed pain levels, wound adherence, bleeding upon
      dressing removal and signs of infection, with chlorhexidine-impregnated tulle
      gras and a lipidocolloid dressing used for primary wound dressing following MCS.
      RESULTS: A total of 42 patients were included. Adherence of the dressing to the
      wound (p<0.001) and bleeding after removal (p=0.001) were significantly higher in
      the chlorhexidine-impregnated tulle gras dressing group. Pain during removal of
      wound dressing had a higher visual analogue scale score (1.9 +/- 2.2) in the
      chlorhexidine-impregnated tulle gras dressing group compared to 0.7 +/- 1.0 in
      the lipidocolloid dressing group (p=0.022). CONCLUSION: The results indicate that
      the lipidocolloid dressing, when compared with the chlorhexidine-impregnated
      tulle gras dressing, offers a significant benefit during removal in terms of less
      pain, less wound adherence and less wound bleeding. DECLARATION OF INTEREST: The
      authors have no conflict of interest to declare.

PMID- 25764959
TI  - A new quality of life consultation template for patients with venous leg
      ulceration.
AB  - OBJECTIVE: Chronic venous leg ulcers (CVLUs) are common and recurrent, however,
      care for patients predominantly has a focus which overlooks the impact of the
      condition on quality of life. The aim of this study was to develop a simple,
      evidence-based consultation template, with patients and practitioners, which
      focuses consultations on quality of life themes. METHOD: A nominal group was
      undertaken to develop a new consultation template for patients with CVLUs based
      on the findings of earlier qualitative study phases. RESULTS: A user-friendly two
      sided A4 template was designed to focus nurse-patient consultations on the
      quality of life challenges posed by CVLUs. CONCLUSION: CVLUs impact negatively on
      the quality of life of the patient but this receives inadequate attention during
      current consultations. This new template will help to ensure that key concerns
      are effectively raised, explored and addressed during each consultation.
      DECLARATION OF INTEREST: The NHS West Midlands Strategic Health Authority funded
      this study. The authors have no conflicts of interest to declare.

PMID- 25764960
TI  - Wound closure in patients with DFU: a cost-effectiveness analysis of two
      cellular/tissue-derived products.
AB  - OBJECTIVE: Determine the cost-effectiveness of extracellular matrix (ECM)
      relative to human fibroblast-derived dermal substitute (HFDS) on diabetic foot
      ulcer (DFU) wound closure. METHOD: Outcomes data were obtained from a 12-week,
      randomised, clinical trial of adults aged 18 years or older diagnosed with type 1
      or type 2 diabetes with a DFU. Patients were treated with either ECM or HFDS
      treatment. A two-state Markov model (healed and unhealed) with a 1-week cycle
      length was developed using wound-closure rates from the trial to estimate the
      number of closed-wound weeks and the expected DFU cost per patient. Results were
      recorded over 12 weeks to estimate the number of closed-wound weeks per treatment
      and the average cost to achieve epithelialisation (primary outcome). The
      perspective of the analysis was that of the payer, specifically the Centers for
      Medicare and Medicaid Services. No cost discounting was performed because of the
      short duration of the study. RESULTS: The study consisted of 26 patients, with 13
      in each group. In the ECM group, 10 wounds closed (77%), with an average closure
      time of 36 days; 11 wounds closed in the HFDS group (85%), with an average
      closure time of 41 days. There was no significant difference between these
      results (p=0.73). Over 12 weeks, the expected cost per DFU was $2522 (L1634) for
      ECM and $3889 (L2524) for HFDS. Patients treated with HFDS incurred total
      treatment costs that were approximately 54% higher than those treated with ECM.
      Sensitivity analyses revealed that the total cost of care for two applications of
      HFDS was more costly than eight applications of ECM by approximately $500 (L325).
      CONCLUSION: In patients with DFU, ECM yielded similar clinical outcomes to HFDS
      but at a lower cost. Health-care providers should consider ECM as a cost-saving
      alternative to HFDS. DECLARATION OF INTEREST: A.M. Gilligan, and C.R. Waycaster,
      are employees of Smith & Nephew Inc.. This study was funded by Smith & Nephew
      Inc.. A.L. Landsman, reports no conflicts of interest.

PMID- 25764961
TI  - Letters.

PMID- 25764962
TI  - Erosive tooth wear among 12-year-old schoolchildren: a population-based cross
      sectional study in Montevideo, Uruguay.
AB  - The aim of this study was to assess the prevalence, extent, severity, intraoral
      distribution and risk indicators for erosive tooth wear (ETW) among 12-year-old
      schoolchildren from Montevideo, Uruguay. A population-based, cross-sectional
      survey was conducted using a representative sample of 1,136 12-year-old
      schoolchildren attending public and private schools. Parents answered questions
      on socioeconomic status and general health. Schoolchildren answered questions on
      dietary and oral hygiene habits. Two calibrated examiners recorded ETW on
      permanent teeth according to the Basic Erosive Wear Examination (BEWE) score
      system. Logistic regression models were performed to assess the association
      between the predictor variables and the prevalence of ETW (overall and severe
      ETW). Odds ratios (OR) and the respective 95% confidence intervals (CI) were
      estimated. The prevalence of ETW was 52.9%, being mild erosion (BEWE = 1) in the
      vast majority of cases (48.5%). Severe erosion (BEWE >=2) was detected in 4.4% of
      schoolchildren. The overall prevalence of ETW differed significantly between
      categories of gender and socioeconomic status, but only between gender in the
      severe ETW analysis. The overall extent of ETW was significantly different
      between categories of gender, socioeconomic status, and swish before swallow. The
      extent of severe ETW differed between categories of swish before swallow and
      brushing frequency. In the logistic regression analysis, no association was found
      between the studied variables and the overall prevalence of ETW. Males were more
      likely to have severe ETW than females (OR = 3.22, 95% CI = 1.50-6.89). ETW may
      be considered a public health problem among 12-year-old-Uruguayan schoolchildren.

PMID- 25764963
TI  - Hispidulin, a constituent of Clerodendrum inerme that remitted motor tics,
      alleviated methamphetamine-induced hyperlocomotion without motor impairment in
      mice.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Previously, we found a patient with an
      intractable motor tic disorder that could be ameliorated by the ground leaf juice
      of Clerodendrum inerme (CI). Furthermore, the ethanol extract of CI leaves
      effectively ameliorated methamphetamine-induced hyperlocomotion (MIH) in mice, an
      animal model mimicking the hyper-dopaminergic status of tic disorders/Tourette
      syndrome, schizophrenia, or obsessive-compulsive disorder. Here, we for the first
      time identified a constituent able to reduce MIH from the CI ethanol extract that
      might represent a novel lead for the treatment of such disorders. MATERIALS AND
      METHODS: The ethanol extract of CI was sub-divided into n-hexane,
      dichloromethane, n-butanol and water fractions. Using MIH alleviation as a
      bioassay, active compounds were identified in these fractions using silica gel
      chromatography, recrystallization and proton NMR spectroscopy. RESULTS: The
      dichloromethane and n-hexane fractions were active in the bioassay. Further
      subfractionation and re-crystallization resulted in an active compound that was
      identified to be hispidulin by proton NMR spectroscopy. Hispidulin significantly
      alleviated MIH in mice at doses that did not affect their spontaneous locomotor
      activity or performance in the rotarod test, a measure for motor coordination.
      CONCLUSIONS: Hispidulin is a flavonoid that has been isolated from several plants
      and reported to have anti-oxidative, anti-inflammatory and anti-cancer
      activities. Here, we for the very first time found that hispidulin can also
      alleviate MIH at doses that did not impair motor activity, suggesting a
      therapeutic potential of hispidulin in hyper-dopaminergic disorders.

PMID- 25764964
TI  - Inhibitory effects of cytochrome P450 enzymes CYP1A2, CYP2A6, CYP2E1 and CYP3A4
      by extracts and alkaloids of Gelsemium elegans roots.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Gelsemium elegans (GE), widely distributed in
      East Asia, South East Asia and Northern America, is a kind of well-known toxic
      plant throughout the world. Yet it has been used as a Chinese folk medicine for
      treatment of malignant tumors, pain, rheumatic arthritis, psoriasis and immune
      function. AIM OF THE STUDY: The present study was to investigate the potential
      inhibitory effects of G. elegans (GE) roots on four major cytochrome P450
      (CYP450) isoforms (CYP1A2, CYP2A6, CYP2E1 and CYP3A4) in vitro. MATERIALS AND
      METHODS: Four extracts (petroleum ether, dichloromethane, EtOAc and aqueous) of
      GE and two commercially available alkaloids (koumine and humantenmine) were
      screened for their CYP isoforms inhibitory activity. Four enzyme inhibition
      assays were examined according to the method of the literature. Phenacetin,
      coumarin, chlorzoxazone and testosterone were used as probe substrates in order
      to determine CYP1A2, CYP2A6, CYP2E1 and CYP3A4 catalytic activity, respectively.
      Each probe substrate was incubated with or without each extract and active
      constituent for corresponding isoform, followed by determination of the kinetics
      parameters, IC50 and Ki, to characterize inhibitory effects. RESULTS: GE
      dichloromethane extract selectively inhibited activities of CYP2E1
      (IC50=29.04ug/ml) and CYP2A6 (IC50=46.84ug/ml), with Ki of 10.16 and 19.33ug/ml,
      respectively. In the case of alkaloids, koumine exhibited significant inhibitory
      effects on CYP2E1 while humantenmine showed more potent inhibition on CYP2E1 and
      CYP2A6 (IC50 of 47.44, 18.34 and 45.87ug/ml, Ki of 31.20, 35.06 and 52.06ug/ml,
      respectively). Because of their relatively high Ki values, the active
      constituents in GE dichloromethane extract were analyzed. The UPLC-DAD-ESI-MS/MS
      data showed that GE dichloromethane extract contains 6 kinds of indole alkaloids
      (koumine, humantenmine, humantenine, humantenirine, N-methoxytaberpsychine, and
      sempervirine). As for CYP1A2 and CYP3A4, the negligible inhibitions were
      observed. CONCLUSION: G. elegans extracts inhibited several CYP450 enzyme
      activities with varying potency. Strong inhibition was observed in CYP2E1 and
      CYP2A6 isoforms by GE dichloromethane extract, koumine and humantenmine,
      inferring the involvement of alkaloids chemical constituents from GE
      dichloromethane extract in the effect.

PMID- 25764965
TI  - Human Dental Pulp Stem Cells. A promising epithelial-like cell source.
AB  - Several models of tissue-engineered human skin based on three-dimensional (3D) co
      culture techniques have been proposed to the date. However, normal skin biopsies
      are not always available, especially in patients with a high percentage of skin
      affected by deep burning, and the generation of large amounts of cultured
      keratinocytes may take very long time, with an associated risk for the patients'
      survival. For those reasons, the search of alternative cell sources for tissue
      reconstruction is a clinical need. In this context, Human Dental Pulp Stem Cells
      (HDPSC) have the potential to differentiate into multiple cell lineages by the
      appropriate differentiation conditions, but skin epidermis differentiation has
      not been demonstrated so far. Here, we hypothesize that HDPSC may have
      pluripotent differentiation capability, and may be able to differentiate into
      skin epithelial keratinocytes in culture using organotypic 3D models based on the
      interaction with the subjacent dermal fibroblasts. By using HDPSC, the problems
      associated to the donor site availability and the proliferation capability of the
      epithelial cells could be solved. The rapid accessibility to these cells could be
      translated to a more immediate generation of a bioengineered human skin
      substitute for the future clinical treatment. 

PMID- 25764966
TI  - Evaluating response to disease-modifying therapy in relapsing multiple sclerosis.
AB  - Despite the broadening range of available treatments, the response of multiple
      sclerosis patients to disease-modifying therapies remains quite heterogeneous,
      thus a scheme is required in order to flag individuals achieving a suboptimal
      treatment response, so that they may switch to a different, possibly more
      effective disease-modifying therapy. There are several treatment outcomes that
      can be defined as surrogate markers for continued treatment efficacy and can be
      used for optimizing disease-modifying therapy. As no single marker is validated,
      we must make use of all available potential surrogates to help predict the future
      course of the disease. Only by putting all of the outcome measures together can a
      true picture be derived that will indicate an optimal response to treatment. 

PMID- 25764967
TI  - Tachycardia in breast reconstructive microsurgery: Affirmation of the IMA
      tachycardia syndrome.
AB  - INTRODUCTION: The internal mammary vessels are frequently chosen as recipient
      vessels for breast free flap reconstruction. We have noticed that when using the
      internal mammary recipients that these patients have a propensity for tachycardia
      that was not previously observed. Our aim was to investigate the factors related
      to perioperative tachycardia in the microsurgical breast reconstruction
      population and to address whether use of the internal mammary system is a
      causative factor in tachycardia. METHODS: A retrospective chart review was
      conducted to identify patients who underwent abdominal-based microvascular breast
      reconstruction at the Washington University School of Medicine between 2002 and
      2012 to identify the presence of tachycardia. After application of exclusion
      criteria, 76 microvascular abdominal-based free flap reconstructions were
      identified. The internal mammary (IM) TRAM group (n = 24) and the thoracodorsal
      (TD) TRAM group (n = 52) were compared. A binomial logistic regression was
      performed with the presence of tachycardia as the dependent variable. RESULTS:
      There was a higher incidence of tachycardia in the IM TRAM group when compared to
      the TD TRAM group (p = 0.004). The variables predictive of tachycardia in our
      logistic regression model were IMA recipient (p = 0.04), need for transfusion (p
      = 0.03), and presence of fever (p = 0.01). CONCLUSION: Our study reaffirms that
      there are several factors that are predictive of tachycardia in the setting of
      microvascular breast reconstruction. The IMA syndrome should be a recognized
      cause of tachycardia as using these recipient vessels are shown to be predictive
      of postoperative tachycardia as shown in our study.

PMID- 25764968
TI  - Commentary to diagnosing PIP breast implant failure: a prospective analysis of
      clinical and ultrasound accuracy.

PMID- 25764969
TI  - Bacillus amyloliquefaciens strain 32a as a source of lipopeptides for biocontrol
      of Agrobacterium tumefaciens strains.
AB  - AIMS: A Bacillus amyloliquefaciens strain, designated 32a, was used to identify
      new compounds active against Agrobacterium tumefaciens and to evaluate their
      efficiency to control crown gall on carrot discs. METHODS AND RESULTS: Based on
      PCR-assays, four gene clusters were shown to direct the synthesis of the cyclic
      lipopeptides surfactin, iturin A, bacillomycin D and fengycin. Mass spectrometry
      analysis of culture supernatant led to the identification of these secondary
      metabolites, except bacillomycin, with heterogeneous mixture of homologues.
      Antimicrobial assays using lipopeptides-enriched extract showed a strong
      inhibitory activity against several bacterial and fungal strains, including Ag.
      tumefaciens. Biological control assays on carrot discs using both 32a spores and
      extract resulted in significant protection against crown gall disease, similar to
      that provided by the reference antagonistic strain Agrobacterium rhizogenes
      K1026. CONCLUSIONS: In contrast to all active compounds against Ag. tumefaciens
      that are of proteinaceous nature, this work enables for the first time to
      correlate the strong protective effect of B. amyloliquefaciens strain 32a towards
      crown gall disease with the production of a mixture of lipopeptides. SIGNIFICANCE
      AND IMPACT OF THE STUDY: The findings could be useful for growers and nursery men
      who are particularly interested in the biocontrol of the crown gall disease.

PMID- 25764970
TI  - Apoptotic effect of novel Schiff based CdCl2(C14H21N3O2) complex is mediated via
      activation of the mitochondrial pathway in colon cancer cells.
AB  - The development of metal-based agents has had a tremendous role in the present
      progress in cancer chemotherapy. One well-known example of metal-based agents is
      Schiff based metal complexes, which hold great promise for cancer therapy. Based
      on the potential of Schiff based complexes for the induction of apoptosis, this
      study aimed to examine the cytotoxic and apoptotic activity of a
      CdCl2(C14H21N3O2) complex on HT-29 cells. The complex exerted a potent
      suppressive effect on HT-29 cells with an IC50 value of 2.57 +/- 0.39 after 72 h
      of treatment. The collapse of the mitochondrial membrane potential and the
      elevated release of cytochrome c from the mitochondria to the cytosol indicate
      the involvement of the intrinsic pathway in the induction of apoptosis. The role
      of the mitochondria-dependent apoptotic pathway was further proved by the
      significant activation of the initiator caspase-9 and the executioner caspases-3
      and -7. In addition, the activation of caspase-8, which is associated with the
      suppression of NF-kappaB translocation to the nucleus, also revealed the
      involvement of the extrinsic pathway in the induced apoptosis. The results
      suggest that the CdCl2(C14H21N3O2) complex is able to induce the apoptosis of
      colon cancer cells and is a potential candidate for future cancer studies.

PMID- 25764972
TI  - Influence of the surface structure of graphene oxide on the adsorption of
      aromatic organic compounds from water.
AB  - In this work, graphene oxide (GO) has been employed as an efficient adsorbent for
      the removal of three aromatic organic compounds (AOCs), namely, aniline,
      nitrobenzene, and chlorobenzene, from water under various initial AOC
      concentrations and pH levels. Based on the characteristics of surface structures
      of GO, a simple semiquantitative model has been provided to describe the
      intrinsic adsorption behavior of GO to AOCs. Accordingly, the adsorption
      mechanism has been discussed in detail at molecular levels. The contribution
      coefficients derived from the proposed model indicate that the most preferential
      interactions between GO and AOCs are hydrophobic interactions (pi-pi stacking and
      hydrophobic effect) that occur on graphitic zones of GO (unoxidized region). In
      the oxidized region, there also exist the hydrophobic interactions on sp(2)
      clusters, although they may be hindered by surrounding sp(3) zones which are the
      most unfavorable and are only accessible to AOCs through hydrogen bonding or
      electrostatic effects. More interestingly, aniline exhibits the highest
      contribution coefficients in both hydrophobic and hydrophilic zones of GO among
      the three measured AOCs due to its good water solubility and facile formation of
      hydrogen bonds. Furthermore, the analytical results of the adsorption isotherms
      are also fully consistent with those from the proposed model. 

PMID- 25764971
TI  - Autophagy Controls Acquisition of Aging Features in Macrophages.
AB  - Macrophages provide a bridge linking innate and adaptive immunity. An increased
      frequency of macrophages and other myeloid cells paired with excessive cytokine
      production is commonly seen in the aging immune system, known as 'inflamm-aging'.
      It is presently unclear how healthy macrophages are maintained throughout life
      and what connects inflammation with myeloid dysfunction during aging. Autophagy,
      an intracellular degradation mechanism, has known links with aging and lifespan
      extension. Here, we show for the first time that autophagy regulates the
      acquisition of major aging features in macrophages. In the absence of the
      essential autophagy gene Atg7, macrophage populations are increased and key
      functions such as phagocytosis and nitrite burst are reduced, while the
      inflammatory cytokine response is significantly increased - a phenotype also
      observed in aged macrophages. Furthermore, reduced autophagy decreases surface
      antigen expression and skews macrophage metabolism toward glycolysis. We show
      that macrophages from aged mice exhibit significantly reduced autophagic flux
      compared to young mice. These data demonstrate that autophagy plays a critical
      role in the maintenance of macrophage homeostasis and function, regulating
      inflammation and metabolism and thereby preventing immunosenescence. Thus,
      autophagy modulation may prevent excess inflammation and preserve macrophage
      function during aging, improving immune responses and reducing the morbidity and
      mortality associated with inflamm-aging.

PMID- 25764975
TI  - Uterus-Like Mass: Issues on Pathogenesis.

PMID- 25764973
TI  - GASS: genome structural annotation for Eukaryotes based on species similarity.
AB  - BACKGROUND: With the development of high-throughput sequencing techniques, more
      and more genomes were sequenced and assembled. However, annotating a genome's
      structure rapidly and expressly remains challenging. Current eukaryotic genome
      annotations require various, abundant supporting data, such as: species-specific
      and cross-species protein sequences, ESTs, cDNA and RNA-Seq data. Collecting
      those data and merging their analytical results to achieve a consistent complete
      annotation is a complex, time and cost consuming task. RESULTS: In our study, we
      proposed a fast and easy-to-use computational tool: GASS (Genome Annotation based
      on Species Similarity). It annotates a eukaryotic genome based on only the
      annotations from another similar species. With aligning the exons' sequences of
      an annotated similar species to the un-annotated genome, GASS detects the optimal
      transcript annotations with a shortest-path model. In our study, GASS was used to
      achieve the rhesus annotations based on the human annotations. The produced
      annotations were evaluated by comparing them to the two existing rhesus
      annotation databases (RefSeq and Ensembl) directly and being aligned with three
      RNA-Seq data of rhesus. The experiment results showed that more than 65% RefSeq
      exons and splicing junctions were exactly found by GASS. GASS's sensitivity was
      higher than RefSeq's, and was close to Ensembl's. GASS had higher specificities
      than Ensembl at gene, transcript, exon and splicing junction levels. We also
      found the mis-assemblies of rheMac3 genome, which led to the 2 bp shifts in
      annotating position on exons' boundary and then the incomplete splicing canonical
      sites in Refseq annotations. These detections were further supported by various
      data sources. CONCLUSIONS: GASS quickly produces structural genome annotations in
      sufficient abundance and accuracy. With simple and rapid running of GASS, small
      labs can create quick views of genome annotations for an un-annotated species,
      without the necessity to create, collect, analyze and synthesize extra various
      data sources, or wait several months for the annotations from professional
      organizations. GASS can be applied to many study occasions, such as the analysis
      of RNA-Seq datasets from the unannotated species whose genome drafts are
      available but the annotations are not.

PMID- 25764974
TI  - Laparoscopic Treatment of Sclerosing Stromal Tumor of the Ovary in a Woman With
      Gorlin-Goltz Syndrome: A Case Report and Review of the Literature.
AB  - Gorlin-Goltz syndrome is a rare hereditary multisystemic disease. Multiple basal
      cell carcinomas, odontogenic keratocysts, and skeletal abnormalities are the main
      clinical manifestations of the syndrome, but several organs can be involved.
      Moreover, this condition is associated with the development of various benign and
      malignant tumors, even in the genital tract. This report describes a rare
      association between Gorlin-Goltz syndrome and the sclerosing stromal tumor of the
      ovary. Because the ultrasound and magnetic resonance imaging patterns of this
      tumor can be similar to those of a malignant neoplasm, prompt surgical
      intervention and histological confirmation of diagnosis is mandatory; however,
      this is a benign lesion and thus can be approached with a laparoscopic fertility
      sparing surgery. Gynecologists should be aware of this possible association to
      provide appropriate counseling for these women, and to take a fertility-sparing
      laparoscopic approach whenever possible. 

PMID- 25764976
TI  - Laparoscopic and Robotic-assisted Vesicovaginal Fistula Repair: A Systematic
      Review of the Literature.
AB  - Two types of laparoscopic or robotic-assisted vesicovaginal fistula (VVF)
      repairs, the traditional transvesical (O'Conor) and extravesical techniques,
      dominate the literature. The objectives of this study are to compare success
      rates between laparoscopic or robotic transvesical and extravesical laparoscopic
      VVF repair techniques and to evaluate the impact of the number of layers in the
      closure, interposition flaps, and intraoperative testing of the integrity of the
      bladder repair. Eligible studies, published between 1994 and March 10, 2014, were
      retrieved through Medline and bibliography searches. All study designs of
      laparoscopic/robotic VVF repair were included. Open laparotomy and vaginal
      approaches were excluded. Only 1 retrospective cohort study was included, with
      the remaining articles consisting of case reports and case series. Ultimately,
      only 44 studies were included in a systematic review: 9 articles of robotic
      assisted approach, 3 laparoscopic single-site surgeries, and 32 conventional
      laparoscopic approaches. A literature review revealed a balanced number of
      reports for both transvesical and extravesical approaches. Statistical meta
      analysis was not performed because of high heterogeneity. The overall success
      rate of laparoscopic VVF repair was 80% to 100% with a follow-up period of 1 to
      74 months. The success rate of transvesical and extravesical techniques were
      95.89% and 98.04% (relative risk, .98; 95% confidence interval, .94-1.02). There
      was no statistical difference in success rates of VVF repair with different
      number of layers in the fistula closure or with use of interposition flaps, but
      there was a small increase in success in the cases that documented intraoperative
      bladder filling to test the integrity of the bladder closure. In conclusion,
      transperitoneal extravesical VVF repair has cure rates similar to the traditional
      transvesical approach. Laparoscopic extravesical VVF repair is a safe, effective,
      minimally invasive technique with excellent cure rates similar to those of the
      conventional transvesical approach in experienced surgeons' hands.

PMID- 25764977
TI  - Length dependent thermal conductivity measurements yield phonon mean free path
      spectra in nanostructures.
AB  - Thermal conductivity measurements over variable lengths on nanostructures such as
      nanowires provide important information about the mean free paths (MFPs) of the
      phonons responsible for heat conduction. However, nearly all of these
      measurements have been interpreted using an average MFP even though phonons in
      many crystals possess a broad MFP spectrum. Here, we present a reconstruction
      method to obtain MFP spectra of nanostructures from variable-length thermal
      conductivity measurements. Using this method, we investigate recently reported
      length-dependent thermal conductivity measurements on SiGe alloy nanowires and
      suspended graphene ribbons. We find that the recent measurements on graphene
      imply that 70% of the heat in graphene is carried by phonons with MFPs longer
      than 1 micron. 

PMID- 25764978
TI  - The transmembrane Bax inhibitor motif (TMBIM) containing protein family: Tissue
      expression, intracellular localization and effects on the ER CA2+-filling state.
AB  - Bax inhibitor-1 (BI-1) is an evolutionarily conserved pH-dependent Ca2+ leak
      channel in the endoplasmic reticulum and the founding member of a family of six
      highly hydrophobic mammalian proteins named transmembrane BAX inhibitor motif
      containing (TMBIM) 1-6 with BI-1 being TMBIM6. Here we compared the structure,
      subcellular localization, tissue expression and the effect on the cellular Ca2+
      homeostasis of all family members side by side. We found that all TMBIM proteins
      possess the di-aspartyl pH sensor responsible for pH sensing identified in TMBIM6
      and its bacterial homologue BsYetJ. TMBIM1-3 and TMBIM4-6 represent two
      phylogenetically distinct groups that are localized in the Golgi apparatus
      (TMBIM1-3), endoplasmic reticulum (TMBIM4-6) or mitochondria (TMBIM5) but share a
      common structure of at least seven transmembrane domains with the last domain
      being semi-hydrophobic. TMBIM1 is mainly expressed in muscle, TMBIM2 and 3 in the
      nervous system, TMBIM4 and 5 are ubiquitously expressed and TMBIM6 in skeletal
      muscle, kidney, liver and spleen. All TMBIM proteins reduce the Ca2+ content of
      the endoplasmic reticulum, and all but TMBIM5 also reduce the cytosolic resting
      Ca2+ concentration. These results suggest that the TMBIM family has comparable
      functions in the maintenance of intracellular Ca2+ homeostasis in a wide variety
      of tissues. This article is part of a Special Issue entitled: 13th European
      Symposium on Calcium.

PMID- 25764979
TI  - The non-glycosylated isoform of MIC26 is a constituent of the mammalian MICOS
      complex and promotes formation of crista junctions.
AB  - Mitochondrial membrane architecture is important for organelle function.
      Alterations thereof are linked to a number of human disorders including diabetes
      and cardiomyopathy. The MICOS complex was recently reported to be a central
      player determining cristae structure and formation of crista junctions. Here we
      investigated the functional role of MIC26, a lipoprotein formerly termed APOO.
      Its levels are increased in diabetic heart tissue and in blood plasma of patients
      suffering from acute coronary syndrome. We demonstrate that human MIC26 exists in
      three distinct forms: (1) a glycosylated and secreted 55kDa protein, (2) an
      ER/Golgi-resident form thereof, and (3) a non-glycosylated 22kDa mitochondrial
      protein. The latter isoform spans the mitochondrial inner membrane and physically
      interacts with several MICOS complex subunits such as MIC60, MIC27, and MIC10. We
      further demonstrate that MIC26 and MIC27, a homologous protein formerly termed
      APOOL, regulate their levels in an antagonistic manner. Both proteins are
      positively correlated with the levels of MIC10 as well as tafazzin, an enzyme
      required for cardiolipin remodeling. Overexpression of MIC26 induced
      fragmentation of mitochondria, promoted ROS formation and resulted in impaired
      mitochondrial respiration. Downregulation of MIC26 induced a decrease in
      mitochondrial oxygen consumption, whereas mitochondrial network morphology and
      ROS levels remained unaffected. MIC26 depletion led to alterations in
      mitochondrial ultrastructure and caused a significant reduction in the number of
      crista junctions. In summary, we show that the human apolipoprotein MIC26 is a
      bona fide subunit of the MICOS complex and that MIC26 is linked to cardiolipin
      metabolism and promotes crista junction formation. 

PMID- 25764980
TI  - Calcium homeostasis in cancer: A focus on senescence.
AB  - Senescence is one of the primary responses to the activation of oncoproteins or
      down-regulation of tumor suppressors in normal cells and is therefore considered
      as being anti-tumorigenic but the mechanisms controlling this process are still
      much unknown. Calcium (Ca2+) plays a major role in many cellular processes and
      calcium channels control many of the "hallmarks of cancer" but their involvement
      in tumor initiation is poorly understood and remains unclear. Therefore, in this
      article we review some striking senescence-associated characteristics and their
      potential regulation by Ca2+. The main aim is to produce plausible hypothesis on
      how calcium homeostasis may participate in cancer-related senescence. This
      article is part of a Special Issue entitled: 13th European Symposium on Calcium.

PMID- 25764982
TI  - Empirical prediction and validation of antibacterial inhibitory effects of
      various plant essential oils on common pathogenic bacteria.
AB  - In this study, fractional compound composition, antioxidant capacity, and
      phenolic substance content of 14 plant essential oils-anise (Pimpinella anisum),
      bay leaves (Laurus nobilis), cinnamon bark (Cinnamomum verum), clove (Eugenia
      caryophyllata), fennel (Foeniculum vulgare), hop (Humulus lupulus), Istanbul
      oregano (Origanum vulgare subsp. hirtum), Izmir oregano (Origanum onites), mint
      (Mentha piperita), myrtus (Myrtus communis), orange peel (Citrus sinensis), sage
      (Salvia officinalis), thyme (Thymbra spicata), and Turkish oregano (Origanum
      minutiflorum)--were related to inhibition of 10 bacteria through multiple linear
      or non-linear (M(N)LR) models-four Gram-positive bacteria of Listeria innocua,
      coagulase-negative staphylococci, Staphylococcus aureus, and Bacillus subtilis,
      and six Gram-negative bacteria of Yersinia enterocolitica, Salmonella
      Enteritidis, Salmonella Typhimurium, Proteus mirabilis, Escherichia coli O157:H7,
      and Klebsiella oxytoca. A total of 65 compounds with different antioxidant
      capacity, phenolic substance content and antibacterial properties were detected
      with 14 plant essential oils. The best-fit M(N)LR models indicated that relative
      to anise essential oil, the essential oils of oreganos, cinnamon, and thyme had
      consistently high inhibitory effects, while orange peel essential oil had
      consistently a low inhibitory effect. Regression analysis indicated that beta
      bisabolene (Turkish and Istanbul oreganos), and terpinolene (thyme) were found to
      be the most inhibitory compounds regardless of the bacteria type tested.

PMID- 25764983
TI  - Establishment of population-based stroke registry in Ludhiana city, northwest
      India: feasibility and methodology.
AB  - BACKGROUND/AIMS: The Indian Council of Medical Research (ICMR) initiated the Task
      Force Project to evaluate the feasibility of conducting a population-based stroke
      registry in Ludhiana city, Punjab, Northwest India. METHODS: All first-ever,
      stroke patients over 18 years from the city of Ludhiana were included in the
      study from March 26th 2010 to March 25th 2011. Stroke information was collected
      based on the WHO STEPS approach from the participating hospitals, scan centres
      and doctors. Modified Rankin Scale (mRS) was administered by telephonic interview
      at 28 days after stroke. The information on stroke deaths was obtained from the
      Municipal Corporation (MC) office. RESULTS: A total of 905 first-ever stroke
      patients were documented. After excluding duplicate cases and patients from
      outside the city, 493 patients were included. The practical issues identified in
      data collection from these centres were reluctance to take informed consent, lack
      of willingness to share the data, difficulty to identify key persons from each
      centre, retrieving medical records from public hospitals and poor documentation
      of deaths in MC office. CONCLUSION: Population-based stroke registry was feasible
      in an urban population with the above methodology. The issues related to
      feasibility were identified and necessary changes were made for the main phase of
      the registry.

PMID- 25764981
TI  - Pharmacological inhibition of ALDH1A in mice decreases all-trans retinoic acid
      concentrations in a tissue specific manner.
AB  - all-trans retinoic acid (atRA), the active metabolite of vitamin A, is an
      essential signaling molecule. Specifically the concentrations of atRA are
      spatiotemporally controlled in target tissues such as the liver and the testes.
      While the enzymes of the aldehyde dehydrogenase 1A family (ALDH1A) are believed
      to control the synthesis of atRA, a direct relationship between altered ALDH1A
      activity and tissue atRA concentrations has never been shown. To test whether
      inhibition of ALDH1A enzymes decreases atRA concentrations in a tissue specific
      manner, the potent ALDH1A inhibitor WIN 18,446 was used to inhibit ALDH1A
      activity in mice. The ALDH1A expression, atRA formation kinetics, ALDH1A
      inhibition by WIN 18,446 and WIN 18,446 disposition were used to predict the time
      course and extent of inhibition of atRA formation in the testis and liver. The
      effect of WIN 18,446 on atRA concentrations in testis, liver and serum were
      measured following single and multiple doses of WIN 18,446. ALDH1A1 and ALDH1A2
      were responsible for the majority of atRA formation in the testis while ALDH1A1
      and aldehyde oxidase contributed to atRA formation in the liver. Due to the
      different complement of enzymes contributing to atRA formation in different
      tissues and different inhibition of ALDH1A1 and ALDH1A2 by WIN 18,446, WIN 18,446
      caused only a 50% decrease in liver atRA but testicular atRA decreased over 90%.
      Serum atRA concentrations were also reduced. These data demonstrate that
      inhibition of ALDH1A enzymes will decrease atRA concentrations in a tissue
      specific manner and selective ALDH1A inhibition could be used to alter atRA
      concentrations in select target tissues. 

PMID- 25764984
TI  - Theory of plasmon enhanced interfacial electron transfer.
AB  - A particular attempt to improve the efficiency of a dye sensitized solar cell is
      it's decoration with metal nano-particles (MNP). The MNP-plasmon induced
      enhancement of the local field enlarges the photoexcitation of the dyes and a
      subsequent improvement of the charge separation efficiency may result. In a
      recent work (2014 J. Phys. Chem. C 118 2812) we presented a theory of plasmon
      enhanced interfacial electron transfer for perylene attached to a TiO2 surface
      and placed in the proximity of a spherical MNP. These earlier studies are
      generalized here to the coupling of to up to four MNPs and to the use of somewhat
      altered molecular parameters. If the MNPs are placed close to each other strong
      hybridization of plasmon excitations appears and a broad resonance to which
      molecular excitations are coupled is formed. To investigate this situation the
      whole charge injection dynamics is described in the framework of the density
      matrix theory. The approach accounts for optical excitation of the dye coupled to
      the MNPs and considers subsequent electron injection into the rutile TiO2
      cluster. Using a tight-binding model for the TiO2-system with about 10(5) atoms
      the electron motion in the cluster is described. We again consider short optical
      excitation which causes an intermediate steady state with a time-independent
      overall probability to have the electron injected into the cluster. This
      probability is used to introduce an enhancement factor which rates the influence
      of the MNP. Values larger than 500 are obtained. 

PMID- 25764985
TI  - Efficient access to enantiopure 1,3-disubstituted isoindolines from selective
      catalytic fragmentation of an original desymmetrized rigid overbred template.
AB  - An efficient and scalable synthesis of various enantiopure 1,3- disubstituted
      isoindolines is reported. The base catalyzed nucleophilic fragmentation of a
      rigid overbred template is established with various substrates to afford the
      corresponding 1,3-disubstituted isoindoline ester, amide, thioate, 1,3-amino
      alcohol and isoindolylcarboxylic acid. The crucial rigid overbred template is
      synthesized in an optically pure form in multigram scale by asymmetric
      desymmetrization of the corresponding meso compound. 

PMID- 25764987
TI  - Superhydrophobic Surfaces as a Tool for the Fabrication of Hierarchical Spherical
      Polymeric Carriers.
AB  - Hierarchical polymeric carriers with high encapsulation efficiencies are
      fabricated via a biocompatible strategy developed using superhydrophobic (SH)
      surfaces. The carries are obtained by the incorporation of cell/BSA-loaded
      dextran-methacrylate (DEXT-MA) microparticles into alginate (ALG) macroscopic
      beads. Engineered devices like these are expected to boost the development of
      innovative and customizable systems for biomedical and biotechnological purposes.

PMID- 25764988
TI  - Market watch: Upcoming catalysts in Q2 2015.

PMID- 25764986
TI  - Small RNAs derived from tRNAs and rRNAs are highly enriched in exosomes from both
      old and new world Leishmania providing evidence for conserved exosomal RNA
      Packaging.
AB  - BACKGROUND: Leishmania use exosomes to communicate with their mammalian hosts and
      these secreted vesicles appear to contribute to pathogenesis by delivering
      protein virulence factors to macrophages. In other eukaryotes, exosomes were
      found to carry RNA cargo, such as mRNAs and small non-coding RNAs, capable of
      altering recipient cell phenotype. Whether leishmania exosomes also contain RNAs
      which they are able to deliver to bystander cells is not known. Here, we show
      that leishmania exosomes indeed contain RNAs and compare and contrast the RNA
      content of exosomes released by Leishmania donovani and Leishmania braziliensis.
      RESULTS: We purified RNA from exosomes collected from axenic amastigote culture
      supernatant and found that when compared with total leishmania RNA, exosomes
      mainly contained short RNA sequences. Exosomes with intact membranes were capable
      of protecting their RNA cargo from degradation by RNase. Moreover, exosome RNA
      cargo was delivered to host cell cytoplasm in vitro. Sequencing of exosomal RNA
      indicated that the majority of cargo sequences were derived from non-coding RNA
      species such as rRNA and tRNA. In depth analysis revealed the presence of tRNA
      derived small RNAs, a novel RNA type with suspected regulatory functions.
      Northern blotting confirmed the specific and selective enrichment of tRNA-derived
      small RNAs in exosomes. We also identified a number of novel transcripts, which
      appeared to be specifically enriched in exosomes compared to total cell RNA. In
      addition, we observed the presence of sequences mapping to siRNA-coding regions
      in L. braziliensis , but not in L. donovani exosomes. CONCLUSIONS: These results
      show that leishmania exosomes are selectively and specifically enriched in small
      RNAs derived almost exclusively from non-coding RNAs. These exosomes are
      competent to deliver their cargo of novel, potential small regulatory RNAs to
      macrophages where they may influence parasite-host cell interactions. The
      remarkably high degree of congruence in exosomal RNA content between L. donovani
      and L. braziliensis, argues for the presence of a conserved mechanism for
      exosomal RNA packaging in leishmania. These findings open up a new avenue of
      research on non-canonical, small RNA pathways in this trypanosomatid, which may
      elucidate pathogenesis and identify novel therapeutic approaches.

PMID- 25764990
TI  - Solvent response to fluorine-atom reaction dynamics in liquid acetonitrile.
AB  - Time-resolved infra-red (IR) absorption spectroscopy is used to follow the
      production of HF from the reaction of fluorine atoms in liquid acetonitrile
      (CH3CN). Photolysis of dissolved XeF2 using ~50 fs duration, 267 nm laser pulses
      generates F atoms and XeF on prompt (sub-ps) timescales, as verified by broadband
      transient electronic absorption spectroscopy. The fundamental vibrational band of
      HF in solution spans more than 400 cm(-1) around the band centre at 3300 cm(-1),
      and analysis of portions of the time-resolved spectra reveals time constants for
      the rise in HF absorption that become longer to lower wavenumber. The time
      constants for growth of 40 cm(-1) wide portions of the IR spectra centred at
      3420, 3320 and 3240 cm(-1) are, respectively, 3.04 +/- 0.26, 5.48 +/- 0.24 and
      7.47 +/- 0.74 ps (1 SD uncertainties). The shift to lower wavenumber with time
      that causes these changes to the time constants is attributed to evolution of the
      micro-solvation environment of HF following the chemical reaction. The initial
      growth of the high-wavenumber portion of the band may contain a contribution from
      relaxation of initially vibrationally excited HF, for which a time constant of
      2.4 +/- 0.2 ps is deduced from IR pump and probe spectroscopy of a dilute HF
      solution in acetonitrile. 

PMID- 25764989
TI  - Quantum dot display enhances activity of a phosphotriesterase trimer.
AB  - Phosphotriesterase was engineered into a spontaneously forming trimer by
      appending it to a synthetic collagen-like triple-helix motif. Enzymatic
      hydrolysis of the insecticide and organophosphate nerve agent simulant paraoxon
      was then examined. Assembling the phosphotriesterase trimer onto semiconductor
      quantum dots increased the enzyme's catalytic rate and efficiency. 

PMID- 25764991
TI  - Health Claims for Food Supplements and Degree of Evidence.

PMID- 25764992
TI  - Prenatal Diagnosis of Renal Vein Thrombosis: A Case Report and Literature Review.
AB  - BACKGROUND: Renal vein thrombosis (RVT) is a well-characterized condition among
      neonates; however, this complication is rarely diagnosed prenatally. METHODS: In
      this report, we describe a fetus with unilateral RVT and summarize the literature
      regarding prenatal diagnostic criteria and postnatal prognosis. We searched the
      English, French and Spanish literature (MEDLINE, PubMed and EMBASE) for cases
      with prenatal diagnosis of RVT. RESULTS: Including our case, a total of 23
      fetuses with fetal RVT were reviewed in the present study. All cases were
      diagnosed in the third trimester, and the survival rate among these cases was
      63%. Enlargement of the kidney was the most commonly associated initial
      ultrasound finding. The only ultrasound finding significantly associated with
      mortality was the presence of bilateral RVT. DISCUSSION: The etiology of fetal
      RVT is still unclear. Considering the large number of cases with RVT that
      manifest in the first days of life, prenatal diagnosis of this condition has
      relevance.

PMID- 25764994
TI  - Relationship between N-terminal B-type natriuretic propeptide and right
      ventricular performance assessed by tissue Doppler imaging and speckle tracking
      echocardiography in children after surgical repair of tetralogy of Fallot.
AB  - BACKGROUND AND AIM: The relationship between plasma levels of N-terminal B-type
      natriuretic propeptide (NT-proBNP) and parameters of right ventricular (RV)
      function was evaluated in patients after surgical repair of tetralogy of Fallot
      (ToF). METHODS: 52 children comprised the study group (SG). The control group
      (CG) included 32 healthy children. Patient histories, measured NT-proBNP levels
      and transthoracic echocardiography parameters were analysed. RESULTS: Tissue
      Doppler imaging (TDI) demonstrated significant differences (p < 0.01) between SG
      and CG in regard to the following systolic and diastolic function parameters:
      peak systolic myocardial velocity (S', 5.9 +/- 1.6 cm/s vs. 9.8 +/- 2.3 cm/s),
      peak early diastolic velocity (E', 6.6 +/- 2.9 cm/s vs. 11.6 +/- 3.1 cm/s), and
      peak atrial diastolic velocity (A', 3.8 +/- 1.6 cm/s vs. 6.6 +/- 2.8 cm/s). Mean
      values of peak longitudinal strain (e) were significantly higher (p < 0.01) in SG
      compared to CG, including basal lateral segment (BL, -32.8 +/- 12.1% vs. -51.5 +/
      15.5%), medial lateral segment (ML, -23.8 +/- 9.5% vs. -40.4 +/- 14.9%), and
      apical lateral segment (AL, -16.9 +/- 7.5% vs. -35.8 +/- 13.43%). Mean plasma NT
      proBNP level also differed significantly (p < 0.01) between SG and CG (286.0 +/-
      269.2 pg/mL vs. 153.1 +/- 170.5 pg/mL, respectively). NT-proBNP levels were
      significantly higher (p < 0.01) in SG subjects with reduced effort tolerance
      (639.2 +/- 357.1 pg/mL) compared to those with normal effort tolerance (181.8 +/-
      97.2 pg/mL), and in patients in whom a transannular patch was used for surgical
      correction (488.9 +/- 317.19 pg/mL) compared to those treated without the use of
      a transannular patch (228.1 +/- 217.5 pg/mL). Significant correlations between
      plasma NT-proBNP level and S' (r = -0.40, p < 0.01), E' (r = -0.50, p < 0.01), BL
      e (r = 0.36, p < 0.05), and AL e (r = 0.35, p < 0.05) were found. CONCLUSIONS: 1.
      Increased plasma NT-proBNP levels in patients after surgical repair of ToF are
      related to RV systolic dysfunction, as determined by the S' wave velocity of the
      tricuspid annulus and longitudinal strain of the RV. 2. Children after surgical
      repair of ToF showed increased plasma NT-proBNP levels associated with RV
      diastolic dysfunction as evaluated by TDI.

PMID- 25764995
TI  - A 75-year pictorial history of the Cayo Santiago rhesus monkey colony.
AB  - This article presents a pictorial history of the free-ranging colony of rhesus
      monkeys (Macaca mulatta) on Cayo Santiago, Puerto Rico, in commemoration of the
      75th anniversary of its establishment by Clarence R. Carpenter in December 1938.
      It is based on a presentation made by the authors at the symposium, Cayo
      Santiago: 75 Years of Leadership in Translational Research, held at the 36th
      Annual Meeting of the American Society of Primatologists in San Juan, Puerto
      Rico, on 20 June 2013.

PMID- 25764996
TI  - Dietary Energy Intake, Body Composition and Resting Energy Expenditure in
      Prepubertal Children with Prader-Willi Syndrome before and during Growth Hormone
      Treatment: A Randomized Controlled Trial.
AB  - BACKGROUND/AIMS: Dietary management is a difficult but key aspect of care in
      children with Prader-Willi syndrome (PWS). We therefore investigated the effect
      of growth hormone (GH) treatment on reported energy intake in children with PWS,
      in relation with body composition, resting energy expenditure (REE) and hormone
      levels. METHODS: In a randomized controlled GH trial including 47 children with
      PWS, we assessed 5-day dietary records and dual-energy X-ray absorptiometry for
      body composition. REE was calculated by Muller's equation, based on fat mass, fat
      free mass and gender. RESULTS: Baseline energy intake of children with PWS was
      lower than normal daily energy requirements (p < 0.001), and decreased with age
      to 50% in prepubertal children. Energy intake in infants [m/f: 11/8; median
      (interquartile range [IQR]) age 2.7 years (1.5-3.2)] increased after 1 year of GH
      treatment (p = 0.008); this tended to be higher in the GH group than in the
      untreated group (p = 0.07). In prepubertal children [m/f: 14/14; median (IQR) age
      6.8 years (5.1-8.1)], the increase in energy intake was higher in the GH group,
      but this was not different compared to the untreated group. REE was not different
      between the GH group and the untreated group. Increase in energy intake during 2
      years of GH treatment was correlated with lower fat percentage standard deviation
      scores (p = 0.037) and higher adiponectin levels (p = 0.007). CONCLUSION: Our
      study demonstrates that parents of children with PWS are very well capable of
      restricting energy intake up to 50% compared to daily energy requirements for age
      and sex-matched healthy children. GH treatment was associated with a slight
      increase in energy intake, but also improved body composition and adiponectin
      levels, which suggests a protective effect of GH treatment.

PMID- 25764997
TI  - Commercialization of graphene-based technologies: a critical insight.
AB  - Carbon in its single layer atomic morphology has exceptional thermal, optical,
      electronic and mechanical properties, which may form the basis for several
      functional products and enhanced technologies that go from electricity storage to
      polymer nanocomposites of so far unsurpassed characteristics. Due to the high
      cost, however, the current global production of graphene does not exceed 120
      tonnes. New chemical and physical methods to exfoliate graphite, however, were
      recently engineered and commercialized, which open the route to massive adoption
      of graphene as the "enabler" of numerous important technologies, including
      enhanced electricity storage. This feature article presents an updated, critical
      overview that will be useful to nanochemistry and nanotechnology research
      practitioners and to entrepreneurs in advanced materials. 

PMID- 25764998
TI  - Determinants of clinical effectiveness and significant neurological diagnoses in
      an urgent brain cancer referral pathway in the United Kingdom.
AB  - BACKGROUND: Cerebral tumours can rapidly progress to life-threatening
      complications yet referral pathways often result in non-significant diagnoses. We
      aimed to identify the determinants of referrals resulting in significant
      neurological diagnoses after specialist review. METHODS: We reviewed all urgent
      brain cancer referrals to the neurology service at a British district general
      hospital between January 2009 and September 2013. Time to appointment, frequency
      of significant neurological diagnoses, appropriateness of referrals and referral
      heterogeneity across GP practices were measured as determinants of non
      significant diagnoses. RESULTS: 31/105 patients received significant neurological
      diagnoses (29.5%), including ten (9.5%) tumours (7 malignant), although 2
      patients were admitted prior to clinic. There was significant heterogeneity
      between primary care physicians in referral frequency (p = 0.008) and significant
      diagnoses (p = 0.005). Non-significant diagnoses were more common in
      inappropriate referrals and if patients were unaware of the potential diagnosis.
      Seizures or subacute focal symptoms were more likely to result in a significant
      neurological diagnosis than isolated headache syndromes (odds ratio 3.45, 1.34
      18.4, p = 0.008). DISCUSSION: Despite a significant number of important
      neurological diagnoses and tumours, there were frequent inappropriate or low-risk
      referrals resulting in non-significant diagnoses, particularly if a headache
      syndrome was the sole reason for referral.

PMID- 25764999
TI  - The spread of primary late-onset focal dystonia in a long-term follow up study.
AB  - OBJECTIVES: To determine spread of primary late-onset focal dystonia at a long
      term follow up study. METHODS: Available patients not lost to follow up from the
      initial cohort were reexamined to access course and spread of dystonia. In this
      prolonged follow-up (13.71 +/- 5.6 years), it was possible to contact and include
      66 out of 132 consecutive patients (50%) who had been diagnosed as primary focal
      dystonia at the Clinic of Neurology (Belgrade) from January 1990 to January 2000.
      RESULTS: Recalculation after inclusion of the new data for 66 patients revealed
      that the latency from the disease onset to dystonia spreading to the first new
      region was 4.9 +/- 4.9 years, and to the second region 5.9 +/- 8.8 years. An
      average time to disease progression was 12.39 +/- 1.58, 6.34 +/- 1.55 and 15.95
      +/- 1.43 for patients with torticollis, blepharospasm, and those with hand
      dystonia, respectively. The spread of dystonia in patients with the initial
      blepharospasm was faster, while patients with the writer's cramp could expect
      further progression even after longer periods of time. Older age at onset (p =
      0.061), family history (p = 0.028) and the presence of tremor in the region
      affected by dystonia (p = 0.047) were the most powerful predictors of disease
      spreading. The majority of spreading events occurred during the first years of
      the disease and they appeared to be rare in later period. CONCLUSIONS: These
      findings may be valuable for prognostic information on the disorder.

PMID- 25765000
TI  - Microhomology-mediated microduplication in the y chromosomal azoospermia factor a
      region in a male with mild asthenozoospermia.
AB  - Y chromosomal azoospermia factor (AZF) regions AZFa, AZFb and AZFc represent
      hotspots for copy number variations (CNVs) in the human genome; yet the number of
      reports of AZFa-linked duplications remains limited. Nonallelic homologous
      recombination has been proposed as the underlying mechanism of CNVs in AZF
      regions. In this study, we identified a hitherto unreported microduplication in
      the AZFa region in a Japanese male individual. The 629,812-bp duplication
      contained 22 of 46 exons of USP9Y, encoding the putative fine tuner of
      spermatogenesis, together with all exons of 3 other genes/pseudogenes. The
      breakpoints of the duplication resided in the DNA/TcMar-Tigger repeat and
      nonrepeat sequences, respectively, and were associated with a 2-bp microhomology,
      but not with short nucleotide stretches. The breakpoint-flanking regions were not
      enriched with GC content, palindromes, or noncanonical DNA structures. Semen
      analysis of the individual revealed a normal sperm concentration and mildly
      reduced sperm motility. The paternal DNA sample of the individual was not
      available for genetic analysis. The results indicate that CNVs in AZF regions can
      be generated by microhomology-mediated break-induced replication in the absence
      of known rearrangement-inducing DNA features. AZFa-linked microduplications
      likely permit production of a normal amount of sperm, although the precise
      clinical consequences of these CNVs await further investigation.

PMID- 25765001
TI  - Association of FPGS genetic polymorphisms with primary retroperitoneal
      liposarcoma.
AB  - Primary retroperitoneal liposarcoma is generally regarded as a genetic disorder.
      We have retrospectively genotyped 8 single nucleotide polymorphisms (SNPs) in 6
      candidate genes (MDM2, CDK4, CDC27, FPGS, IGFN1, and PRAMEF13) in 138 patients
      and 131 healthy control subjects to evaluate the effects of genetic factors on
      individual susceptibility to primary retroperitoneal liposarcoma in Chinese
      population. Three SNPs (rs2870820, rs1695147, rs3730536) of MDM2 showed
      significant differences in single-loci genotypes and allele frequencies between
      case and control groups (p < 0.05). The minor allele G of SNP rs10760502 in FPGS
      (folylpolyglutamate synthase) gene was significantly associated with increased
      risk for primary retroperitoneal liposarcoma, compared with major allele A. Our
      data suggest that FPGS variant in Chinese population may affect individual
      susceptibility to primary retroperitoneal liposarcoma.

PMID- 25765002
TI  - Vaccinia virus protein A3 is required for the production of normal immature
      virions and for the encapsidation of the nucleocapsid protein L4.
AB  - Maturation of the vaccinia virion is an intricate process that results in the
      organization of the viroplasm contained in immature virions into the lateral
      bodies, core wall and nucleocapsid observed in the mature particles. It is
      unclear how this organization takes place and studies with mutants are
      indispensable in understanding this process. By characterizing an inducible
      mutant in the A3L gene, we revealed that A3, an inner core wall protein, is
      important for formation of normal immature viruses and also for the correct
      localization of L4, a nucleocapsid protein. L4 did not accumulate in the viral
      factories in the absence of A3 and was not encapsidated in the particles that do
      not contain A3. These data strengthen our previously suggested hypothesis that A3
      and L4 interact and that this interaction is critical for proper formation of the
      core wall and nucleocapsid. 

PMID- 25765004
TI  - Novel expression and regulation of TIMP-1 in Epstein Barr virus-infected cells
      and its impact on cell survival.
AB  - Epstein Barr virus (EBV) uses various strategies to manipulate host cytokine
      production in favor of the survival of infected B-cells. Microarray and cytokine
      protein array assays revealed that tissue inhibitor of metalloproteinase-1 (TIMP
      1) was significantly up-regulated in EBV-infected primary B cells and maintained
      in abundance in EBV-immortalized lymphoblastoid cell lines (LCLs). TIMP-1 plays
      critical roles in extracellular matrix homeostasis and regulates signaling
      pathways. In this study, we demonstrated that the EBV-encoded immediate early
      lytic protein, Zta, upregulates mainly TIMP-1 expression by binding to the AP-1
      site within the TIMP-1 promoter. Moreover, knockdown of TIMP-1 expression
      promoted cisplastin and cold shock-induced death of LCLs. This study provides a
      mechanistic link between EBV-induced TIMP-1 expression and its impact on LCL
      survival. 

PMID- 25765003
TI  - An unbiased proteomics approach to identify human cytomegalovirus RNA-associated
      proteins.
AB  - Post-transcriptional events regulate herpesvirus gene expression, yet few
      herpesvirus RNA-binding proteins have been identified. We used an unbiased
      approach coupling oligo(dT) affinity capture with proteomics to identify viral
      RNA-associated proteins during infection. Using this approach, we identified and
      confirmed changes in the abundance or activity of two host RNA-associated
      proteins, DHX9 and DDX3, in cells infected with human cytomegalovirus (HCMV). We
      also identified and confirmed previously unreported activities for the HCMV US22
      and pp71 proteins as RNA-associated viral proteins and confirmed that a known
      viral RNA-binding protein, pTRS1, associates with RNA in infected cells. Further,
      we found that HCMV pp71 co-sedimented with polysomes, associated with host and
      viral RNAs, and stimulated the overall rate of protein synthesis. These results
      demonstrate that oligo(dT) affinity capture coupled with proteomics provides a
      rapid and straightforward means to identify RNA-associated viral proteins during
      infection that may participate in the post-transcriptional control of gene
      expression. 

PMID- 25765005
TI  - Interleukin 6 inhibits HBV entry through NTCP down regulation.
AB  - Hepatitis B virus (HBV) infection is a major public health problem. Recently, the
      human liver bile acid transporter Na(+)/taurocholate cotransporting polypeptide
      (NTCP) has been identified as an HBV specific receptor. NTCP expression is known
      to be strongly regulated by IL-6. This study was aimed at characterizing the
      effect of IL-6 on HBV entry. HBV entry was inhibited by up to 90% when cells were
      pretreated with IL-6 as shown by a strong inhibition of long term HBsAg
      secretion. This effect was confirmed by showing a severe reduction of
      intracellular HBV cccDNA. In parallel, we observed a 98% decrease in NTCP mRNA
      steady state level and an 80% reduction in NTCP-mediated taurocholate uptake. IL
      6-mediated inhibition of NTCP-mediated taurocholate uptake and viral entry
      exhibited similar dose-dependence and kinetics while restoration of NTCP
      expression suppressed the inhibitory effect of IL-6. NTCP-mediated HBV entry is
      therefore markedly inhibited by IL-6. 

PMID- 25765006
TI  - Qualifying label components for effective biosensing using advanced high
      throughput SEIRA methodology.
AB  - The need for technological progress in bio-diagnostic assays of high complexity
      requires both fundamental research and constructing efforts on nano-scaled assay
      recognition elements that can provide unique selectivity and design-enhanced
      sensitivity features. Nanoparticle induced sensitivity enhancement and its
      application related to multiplexed capability Surface-Enhanced InfraRed
      Absorption (SEIRA) assay formats are well suitable for these purposes. The
      potential of diverse fluorophore-antibody conjugates, being chemisorbed onto low
      cost gold nanoparticulate SEIRA substrates, has been explored with respect to
      their spectral discriminability. These novel biolabels deliver molecular SEIRA
      fingerprints that have been successfully analyzed by both uni- and multivariate
      analyzing tools, to discriminate their multiplexing capabilities. We show that
      this robust spectral encoding via SEIRA fingerprints opens up new opportunities
      for a fast, reliable and multiplexed high-end screening in biodiagnostics. 

PMID- 25765007
TI  - Evaluating thiophene electron-donor layers for the rapid assessment of boron
      subphthalocyanines as electron acceptors in organic photovoltaics: solution or
      vacuum deposition?
AB  - In this study, we consider the choice of a standard electron-donating material to
      be paired with boron subphthalocyanines (BsubPcs) to rapidly assess the viability
      of new BsubPc derivatives as electron-accepting materials within organic
      photovoltaic devices (OPVs). Specifically, we evaluate the effectiveness of
      solution-cast poly(3-hexylthiophene-2,5-diyl) (P3HT) as an electron donor paired
      with BsubPc derivatives relative to vacuum-deposited sexithiophene (alpha-6T). By
      using fullerene (C60 ), boron subphthalocyanine chloride (Cl-BsubPc), and
      hexachloro boron subphthalocyanine chloride (Cl-Cl6 BsubPc) as electron
      acceptors, we find that devices made with alpha-6T outperform those with P3HT.
      However, the two thiophene-based materials show the same performance trends.
      Given the preservation of these trends, we can recommend either option for
      assessing the potential of new BsubPc derivatives; P3HT as a solution-cast
      electron-donor layer or alpha-6T as a vacuum-deposited alternative. 

PMID- 25765008
TI  - Predicting protein complexes from weighted protein-protein interaction graphs
      with a novel unsupervised methodology: Evolutionary enhanced Markov clustering.
AB  - OBJECTIVE: Proteins are considered to be the most important individual components
      of biological systems and they combine to form physical protein complexes which
      are responsible for certain molecular functions. Despite the large availability
      of protein-protein interaction (PPI) information, not much information is
      available about protein complexes. Experimental methods are limited in terms of
      time, efficiency, cost and performance constraints. Existing computational
      methods have provided encouraging preliminary results, but they phase certain
      disadvantages as they require parameter tuning, some of them cannot handle
      weighted PPI data and others do not allow a protein to participate in more than
      one protein complex. In the present paper, we propose a new fully unsupervised
      methodology for predicting protein complexes from weighted PPI graphs. METHODS
      AND MATERIALS: The proposed methodology is called evolutionary enhanced Markov
      clustering (EE-MC) and it is a hybrid combination of an adaptive evolutionary
      algorithm and a state-of-the-art clustering algorithm named enhanced Markov
      clustering. EE-MC was compared with state-of-the-art methodologies when applied
      to datasets from the human and the yeast Saccharomyces cerevisiae organisms.
      RESULTS: Using public available datasets, EE-MC outperformed existing
      methodologies (in some datasets the separation metric was increased by 10-20%).
      Moreover, when applied to new human datasets its performance was encouraging in
      the prediction of protein complexes which consist of proteins with high
      functional similarity. In specific, 5737 protein complexes were predicted and
      72.58% of them are enriched for at least one gene ontology (GO) function term.
      CONCLUSIONS: EE-MC is by design able to overcome intrinsic limitations of
      existing methodologies such as their inability to handle weighted PPI networks,
      their constraint to assign every protein in exactly one cluster and the
      difficulties they face concerning the parameter tuning. This fact was
      experimentally validated and moreover, new potentially true human protein
      complexes were suggested as candidates for further validation using experimental
      techniques.

PMID- 25765009
TI  - Mesenchymal stem cells as a source of Schwann cells: their anticipated use in
      peripheral nerve regeneration.
AB  - Schwann cells form myelin, sustain axons and provide the microenvironment for
      nerve fibers, thereby playing a key role in the peripheral nervous system (PNS).
      Schwann cells also provide support for the damaged PNS by producing factors that
      strongly promote axonal regrowth and contribute to remyelination, which is
      crucial for the recovery of neural function. These advantages are not confined to
      the PNS and also apply to the central nervous system. Many diseases, including
      peripheral nerve injury, neuropathy, multiple sclerosis and spinal cord injury,
      are targets for Schwann cell therapy. The collection of Schwann cells, however,
      causes new damage to other peripheral nerve segments. Furthermore, the doubling
      time of Schwann cells is not very fast, and thus adequate amounts of Schwann
      cells for clinical use cannot be collected within a reasonable amount of time.
      Mesenchymal stem cells, which are highly proliferative, are easily accessible
      from various types of mesenchymal tissues, such as the bone marrow, umbilical
      cord and fat tissue. Because these cells have the ability to cross oligolineage
      boundaries between mesodermal to ectodermal lineages, they are capable of
      differentiating into Schwann cells with step-by-step cytokine stimulation. In
      this review, we summarize the properties of mesenchymal stem cell-derived Schwann
      cells, which are comparable to authentic Schwann cells, and discuss future
      perspectives.

PMID- 25765010
TI  - Intraovarian control of selective follicular growth and induction of oocyte
      maturation in mammals.
AB  - In newborn mammals, most of the germ cell population rests in a pool of quiescent
      small follicles in the ovaries. Regularly throughout adulthood, a small
      percentage of these oocytes and follicles grows to a certain stage of development
      and then either degenerates or matures and ovulates. This entire process is under
      both exogenous and endogenous control. Recent work, including my laboratory's,
      has clarified that cytokines and glycosaminoglycans are involved as exogenous and
      endogenous factors in ovarian follicular development, atresia, and maturation in
      mammals. The present article describes our contribution regarding the cytokines
      and ovarian glycosaminoglycans that act as intraovarian regulators of follicular
      development and oogenesis, including oocyte maturation, in mammals. 

PMID- 25765011
TI  - Whole-body counter surveys of Miharu-town school children for four consecutive
      years after the Fukushima NPP accident.
AB  - Comprehensive whole-body counter surveys of Miharu-town school children have been
      conducted for four consecutive years, in 2011-2014. This represents the only long
      term sampling-bias-free study of its type conducted after the Fukushima Dai-ichi
      accident. For the first time in 2014, a new device called the Babyscan, which has
      a low (134/137)Cs MDA of <50 Bq/body, was used to screen the children shorter
      than 130 cm. No child in this group was found to have detectable level of
      radiocesium. Using the MDAs, upper limits of daily intake of radiocesium were
      estimated for each child. For those screened with the Babyscan, the upper intake
      limits were found to be ?1 Bq/day for (137)Cs. Analysis of a questionnaire filled
      out by the children's parents regarding their food and water consumption shows
      that the majority of Miharu children regularly consume local and/or home-grown
      rice and vegetables. This however does not increase the body burden. 

PMID- 25765012
TI  - Ca2+ and cAMP regulations of microtubule sliding in hyperactivated motility of
      bull spermatozoa.
AB  - To reach and fertilize the egg, mammalian spermatozoa change their flagellar
      movement in the female reproductive tract, named hyperactivation. The biochemical
      analyses of the hyperactivated movement using demembranated spermatozoa defined
      the factors inducing this peculiar movement; namely, large asymmetrical flagellar
      movement observed in the early stage of the hyperactivation was induced with a
      high Ca(2+) concentration while large symmetrical flagellar movement in the late
      stage of the hyperactivation was generated with low Ca(2+) and high cAMP
      concentrations. Under these conditions, the microtubule sliding of bull sperm
      flagella was investigated by disintegrating the sperm flagella with MgATP(2-)
      after extracting their plasma membrane and mitochondria. The large asymmetrical
      flagellar movement was caused by a long sliding displacement of a fiber of the
      doublet microtubules. On the other hand, the large symmetrical flagellar movement
      was generated by a large amount of microtubule sliding by many doublet
      microtubules. 

PMID- 25765013
TI  - Competition between nucleophilic substitution of halogen (SN Ar) versus
      substitution of hydrogen (SN ArH)-a mass spectrometry and computational study.
AB  - The mechanism of intramolecular gas-phase reactions of N-(2-X-5-nitrophenyl)-N
      methylacetamide carbanions (X=H, F, Cl) has been studied using negative ion
      electrospray mass spectrometry ((-)ESI-MS) technique and modelled
      computationally. It was proven that all three anions form cyclic sigma(H)
      adducts, which undergo elimination of water. In the case of X=F, formation of the
      sigma(F) adduct, leading to SN Ar reaction, was a competing process. This is the
      first proof that also in the gas phase formation of sigma(H) adduct proceeds
      faster than sigma(X) adduct and only when X=F, rates of these two processes are
      comparable. The experimental results are in full agreement with quantum chemical
      calculations. 

PMID- 25765014
TI  - Hysteroscopy as a valid tool for endometrial pathology in patients with
      postmenopausal bleeding or asymptomatic patients with a thickened endometrium:
      hysteroscopic and histological results.
AB  - OBJECTIVE: This study compares hysteroscopic and histopathological results in
      postmenopausal women with abnormal uterine bleeding (AUB) and asymptomatic
      postmenopausal women with a thickened endometrium. MATERIALS AND METHODS: This is
      a retrospective study of 570 cases hysteroscopically examined between January
      2008 and July 2012. The patients were followed up at the Istituto Tumori
      'Giovanni Paolo II', Bari, Italy. RESULTS: A total of 320 of the 570 cases were
      selected. The inclusion criteria were transvaginal ultrasound, hysteroscopy and
      endometrial biopsy. In the AUB group, if the hysteroscopy results were normal, a
      sensitivity, specificity, positive predictive value (PPV) and negative predictive
      value (NPV) of 100, 95, 71 and 100%, respectively, were achieved, while in the
      asymptomatic group these values were 100, 97, 90 and 100%, respectively. For both
      the group with polyps and that with myomas, the sensitivity, specificity, PPV and
      NPV were 100%. For endometrial hyperplasia, hysteroscopy showed a sensitivity,
      specificity, PPV and NPV of 81, 96, 87 and 93%, respectively, in the AUB group,
      while in the asymptomatic group, the sensitivity was 60%, the specificity and PPV
      were 100%, and the NPV was 98%. The sensitivity of hysteroscopy for endometrial
      cancer was 63%, the specificity 97%, the PPV 77%, and the NPV 95%. CONCLUSIONS:
      In postmenopausal women with a thickened endometrium with or without AUB,
      hysteroscopy allows for an accurate diagnosis in benign endometrial pathology.
      Hysteroscopy also allows directed biopsies of suspicious lesions, which is useful
      in malignant endometrial pathology.

PMID- 25765015
TI  - Emotion Regulation of Neuroticism: Emotional Information Processing Related to
      Psychosomatic State Evaluated by Electroencephalography and Exact Low-Resolution
      Brain Electromagnetic Tomography.
AB  - Emotion regulation is the process that adjusts the type or amount of emotion when
      we experience an emotional situation. The aim of this study was to reveal
      quantitative changes in brain activity during emotional information processing
      related to psychosomatic states and to determine electrophysiological features of
      neuroticism. Twenty-two healthy subjects (mean age 25 years, 14 males and 8
      females) were registered. Electroencephalography (EEG) was measured during an
      emotional audiovisual memory task under three conditions (neutral, pleasant and
      unpleasant sessions). We divided the subjects into two groups using the Cornell
      Medical Index (CMI): (CMI-I: control group, n = 10: CMI-II, III or IV:
      neuroticism group, n = 12). We analyzed the digital EEG data using exact low
      resolution brain electromagnetic tomography (eLORETA) current source density
      (CSD) and functional connectivity analysis in several frequency bands (delta,
      theta, alpha, beta, gamma and whole band). In all subjects, bilateral frontal
      alpha CSD in the unpleasant session increased compared to the pleasant session,
      especially in the control group (p < 0.05). CSD of the neuroticism group was
      significantly higher than that of the control group in the full band at the
      amygdala and inferior temporal gyrus, and in the alpha band at the right temporal
      lobe (p < 0.05). Additionally, we found an increase in functional connectivity
      between the left insular cortex and right superior temporal gyrus in all subjects
      during the unpleasant session compared to the pleasant session (p < 0.05). In
      this study, using EEG analysis, we could find a novel cortical network related to
      brain mechanisms underlying emotion regulation. Overall findings indicate that it
      is possible to characterize neuroticism electrophysiologically, which may serve
      as a neurophysiological marker of this personality trait. (c) 2015 S. Karger AG,
      Basel.

PMID- 25765017
TI  - Bioactive glasses-structure and properties.
AB  - Bioactive glasses were the first synthetic materials to show bonding to bone, and
      they are successfully used for bone regeneration. They can degrade in the body at
      a rate matching that of bone formation, and through a combination of apatite
      crystallization on their surface and ion release they stimulate bone cell
      proliferation, which results in the formation of new bone. Despite their
      excellent properties and although they have been in clinical use for nearly
      thirty years, their current range of clinical applications is still small. Latest
      research focuses on developing new compositions to address clinical needs,
      including glasses for treating osteoporosis, with antibacterial properties, or
      for the sintering of scaffolds with improved mechanical stability. This Review
      discusses how the glass structure controls the properties, and shows how a
      structure-based design may pave the way towards new bioactive glass implants for
      bone regeneration. 

PMID- 25765018
TI  - A cost analysis of kidney replacement therapy options in Palestine.
AB  - This study provides a cost analysis of kidney replacement therapy options in
      Palestine. It informs evidence-based resource allocation decisions for government
      funded kidney disease services where transplant donors are limited, and some of
      the common modalities, i.e., peritoneal dialysis (PD) and home hemodialysis (HD),
      are not widely available due to shortages of qualified staff, specialists, and
      centers to follow the patient cases, provide training, make home visits, or
      provide educational programs for patients. The average cost of kidney transplant
      was US$16,277 for the first year; the estimated cost of HD per patient averaged
      US$16,085 per year--nearly as much as a transplant. Consistent with prior
      literature and experience, while live, related kidney donors are scarce, we found
      that kidney transplant was more adequate and less expensive than HD. These
      results have direct resource allocation implications for government-funded kidney
      disease services under Palestinian Ministry of Health. Our findings strongly
      suggest that investing in sufficient qualified staff, equipment, and clinical
      infrastructure to replace HD services with transplantation whenever medically
      indicated and suitable kidney donors are available, as well as deploying PD
      programs and Home HD programs, will result in major overall cost savings. Our
      results provide a better understanding of the costs of kidney disease and will
      help to inform Ministry of Health and related policy makers as they develop short
      and long-term strategies for the population, in terms of both cost savings and
      enhanced quality of life.

PMID- 25765019
TI  - Adipose Tissue-Derived Stem Cells From Obese Subjects Contribute to Inflammation
      and Reduced Insulin Response in Adipocytes Through Differential Regulation of the
      Th1/Th17 Balance and Monocyte Activation.
AB  - Obesity, through low-grade inflammation, can drive insulin resistance and type 2
      diabetes. While infiltration of adipose tissue (AT) with mononuclear cells (MNCs)
      is well established in obesity, the functional consequences of these interactions
      are less understood. Herein, we cocultured human adipose-derived stem cells
      (ASCs) from obese individuals with MNCs and analyzed their reciprocal behavior.
      Presence of ASCs 1) enhanced interleukin (IL)-17A secretion by Th17 cells, 2)
      inhibited gamma-interferon and tumor necrosis factor alpha secretion by Th1
      cells, and 3) increased monocyte-mediated IL-1beta secretion. IL-17A secretion
      also occurred in stromal vascular fractions issued from obese but not lean
      individuals. Th17 polarization mostly depended on physical contacts between ASCs
      and MNCs-with a contribution of intracellular adhesion molecule-1-and occurred
      through activation of the inflammasome and phosphatidylinositol 3-kinase
      pathways. ASCs favored STAT3 over STAT5 transcription factor binding on STAT
      binding sites within the IL-17A/F gene locus. Finally, conditioned media from
      activated ASC-MNC cocultures inhibited adipocyte differentiation mRNA markers and
      impaired insulin-mediated Akt phosphorylation and lipolysis inhibition. In
      conclusion, we report that obese- but not lean-derived ASCs induce Th17 promotion
      and monocyte activation. This proinflammatory environment, in turn, inhibits
      adipogenesis and adipocyte insulin response. The demonstration of an ASC-Th17
      monocyte cell axis reveals a novel proinflammatory process taking place in AT
      during obesity and defines novel putative therapeutic targets. 

PMID- 25765020
TI  - Cross-sectional comparison of point-of-care with laboratory HbA1c in detecting
      diabetes in real-world remote Aboriginal settings.
AB  - OBJECTIVES: To determine if point-of-care (POC) glycated haemoglobin (HbA1c) is
      sufficiently accurate in real-world remote settings to predict or exclude the
      diagnosis of diabetes based on laboratory HbA1c measurements. DESIGN: Cross
      sectional study comparing POC capillary HbA1c results with corresponding venous
      HbA1c levels measured in a reference laboratory. PARTICIPANTS: Aboriginal
      patients >=15 years old who were due for diabetes screening at the participating
      clinics were invited to participate. Two hundred and fifty-five Aboriginal
      participants were enrolled and 241 were included in the analysis. SETTING: 6
      primary healthcare sites in the remote Kimberley region of Western Australia from
      September 2011 to November 2013. MAIN OUTCOME MEASURES: Concordance and mean
      differences between POC capillary blood HbA1c measurement and laboratory
      measurement of venous blood HbA1c level; POC capillary blood HbA1c equivalence
      value for screening for diabetes or a high risk of developing diabetes;
      sensitivity, specificity and positive-predictive value for diagnosing and
      screening for diabetes; barriers to conducting POC testing. RESULTS: Concordance
      between POC and laboratory results was good (rho=0.88, p<0.001). The mean
      difference was -0.15% (95% limits of agreement, -0.67% to 0.36%). POC HbA1c
      measurements >=6.5%, 48 mmol/mol had a specificity of 98.2% and sensitivity of
      73.7% for laboratory measurements >=6.5%. The POC equivalence value for screening
      for diabetes or a high risk of developing diabetes was >=5.7%, 39 mmol/mol
      (sensitivity, 91%; specificity, 76.7% for laboratory measurements >=6.0%, 42
      mmol/mol). Staff trained by other clinic staff 'on the job' performed as well as
      people with formal accredited training. Staff reported difficulty in maintaining
      formal accreditation. CONCLUSIONS: POC HbA1c testing is sufficiently accurate to
      be a useful component in screening for, and diagnosing, diabetes in remote
      communities. Limited local training is adequate to produce results comparable to
      laboratory results and accreditation processes need to reflect this.

PMID- 25765021
TI  - Development of a Synthetic Adaptive Neuro-Fuzzy Prediction Model for Tumor Motion
      Tracking in External Radiotherapy by Evaluating Various Data Clustering
      Algorithms.
AB  - In image guided radiotherapy, in order to reach a prescribed uniform dose in
      dynamic tumors at thorax region while minimizing the amount of additional dose
      received by the surrounding healthy tissues, tumor motion must be tracked in real
      time. Several correlation models have been proposed in recent years to provide
      tumor position information as a function of time in radiotherapy with external
      surrogates. However, developing an accurate correlation model is still a
      challenge. In this study, we proposed an adaptive neuro-fuzzy based correlation
      model that employs several data clustering algorithms for antecedent parameters
      construction to avoid over-fitting and to achieve an appropriate performance in
      tumor motion tracking compared with the conventional models. To begin, a
      comparative assessment is done between seven nuero-fuzzy correlation models each
      constructed using a unique data clustering algorithm. Then, each of the
      constructed models are combined within an adaptive sevenfold synthetic model
      since our tumor motion database has high degrees of variability and that each
      model has its intrinsic properties at motion tracking. In the proposed sevenfold
      synthetic model, best model is selected adaptively at pre-treatment. The model
      also updates the steps for each patient using an automatic model selectivity
      subroutine. We tested the efficacy of the proposed synthetic model on twenty
      patients (divided equally into two control and worst groups) treated with
      CyberKnife synchrony system. Compared to Cyberknife model, the proposed synthetic
      model resulted in 61.2% and 49.3% reduction in tumor tracking error in worst and
      control group, respectively. These results suggest that the proposed model
      selection program in our synthetic neuro-fuzzy model can significantly reduce
      tumor tracking errors. Numerical assessments confirmed that the proposed
      synthetic model is able to track tumor motion in real time with high accuracy
      during treatment. 

PMID- 25765022
TI  - [Pursuing a better role of the journal in improving resident training and
      pathology development in China].

PMID- 25765023
TI  - [Comments on the 2013 update of the consensus on pathologic diagnosis of
      gastrointestinal stromal tumor].

PMID- 25765025
TI  - [Ancillary techniques in refining the diagnosis of hydatidiform mole].

PMID- 25765024
TI  - [Microsatellite instability in colorectal carcinoma:significance and strategy of
      systemic screening].

PMID- 25765026
TI  - [Discrepancies in pathologic evaluation of dyaplasia/early cancer in 60 gastric
      endoscopic submucosal dissection specimens].
AB  - OBJECTIVE: To study the reasons for the discrepancies in pathologic diagnosis of
      gastric dysplasia/early cancer in endoscopic submucosal dissection (ESD)
      specimens, and how to cope with the discrepancies. METHODS: The pathologic
      diagnoses in 60 cases of ESD specimens according to the three currently used
      classification systems (namely Western criteria, Japanese criteria and Vienna
      classification) were compared. The diagnostic discrepancies were analyzed.
      RESULTS: Fifteen of the 17 cases diagnosed as low-grade intraepithelial neoplasia
      according to the Western criteria were revised as adenoma by the Japanese
      criteria. Amongst the 43 cases of gastric intramucosal adenocarcinoma diagnosed
      according to the Japanese criteria, 23 cases had concordant diagnosis by the
      Western criteria. While the diagnosis of low-grade intraepithelial
      neoplasia/adenoma was basically similar irrespective of classification system
      used, there were significant differences in the interpretation of gastric early
      cancer. CONCLUSIONS: The diagnostic discrepancies in the gastric dysplasia/early
      cancer are mainly related to the morphologic criteria applied in different
      classifications. In order to facilitate clinical and pathologic communication, a
      consensus using Vienna/WHO classifications, supplemented with Japanese system, is
      desirable.

PMID- 25765027
TI  - [Clinicopathologic observation of adenoid cystic carcinoma of esophagus].
AB  - OBJECTIVE: To study the clinicopathologic features and differential diagnosis of
      adenoid cystic carcinoma in the esophagus. METHODS: Ten cases of primary adenoid
      cystic carcinoma of the esophagus were retrieved from the archival file. The
      clinicopathologic and immunohistochemical features were studied. The differential
      diagnosis was analyzed. RESULTS: The male-to-female ratio was 9: 1. The age of
      patients ranged from 59 to 76 years. There were 4 cases with tumor located in mid
      esophagus, 4 cases with tumor located in mid to lower esophagus and the remaining
      2 cases in lower esophagus. Low-power histologic examination showed mainly
      expansive growth pattern, with cribriform, solid and focal tubular architectures
      identified. The tumor cells showed nuclear hyperchromasia. Both ductal and
      myoepithelial differentiation was demonstrated. The stroma showed myxoid
      degeneration in areas. Comedo-type necrosis was observed in 8 cases and moderate
      to severe squamous dysplasia was present in one case. Three cases showed focal
      areas of squamous cell carcinoma. Immunohistochemical study showed that the tumor
      cells were positive for p63 (10/10), CD117 (10/10) and S-100 protein (9/10).
      There was focal staining for calponin (2/10) and smooth muscle actin (2/10). The
      ductal structures expressed CK7 (10/10). CONCLUSIONS: Adenoid cystic carcinoma of
      the esophagus demonstrates unique morphologic features with expression of S-100
      protein and consistent expression of CD117. The above characteristics help to
      distinguish this entity from basaloid squamous cell carcinoma, mucoepidermoid
      carcinoma and small cell carcinoma of the esophagus.

PMID- 25765028
TI  - [Adult-onset generalized autoimmune enteropathy involving small intestine and
      colon: report of a case and review of literature].
AB  - OBJECTIVE: To investigate the clinicopathologic features of adult-onset
      autoimmune enteropathy (AIE). METHODS: A case of adult-onset AIE was described
      along with a literature review. RESULTS: A 41-year-old male patient was admitted
      for intractable diarrhea for more than three months despite of any dietary
      restriction or anti-inflammatory therapy. Fat globule was observed by stool
      examination and Sudan III staining of the stool was positive. Enteroclysis showed
      weak movement and few plica of small intestine, while colonoscopy appeared
      normal. Small bowel biopsies revealed villus atrophy and increased crypt
      apoptotic bodies and lymphocytic infiltration in deep crypt. Although without
      significant surface intro-epithelial lymphocytosis, there were a large number of
      monocytes, lymphocytes, plasmacytes and neutrophilic granulocytes infiltrating in
      the lamina propria. Morphologically, the colonic mucous was similar to the small
      intestine although cryptitis and crypt abscess were significant in the former.
      Serum IgG anti-goblet cell antibody was demonstrated by indirect
      immunofluorescence. Other causes of diarrhea were excluded on the base of medical
      history, histopathology and other accessory examinations before the diagnosis of
      AIE was made. The patient had a complete remission after steroid treatment
      without recurrence for eight months during the follow-up even after steroid
      withdrawal for five months. CONCLUSIONS: AIE is exceedingly rare and timely
      diagnosis is important for successful therapy. Histological differential
      diagnoses should include ulcerative colitis, celiac disease, lymphocytic colitis,
      etc. The final diagnosis should be based on histological examination combined
      with the patient history, clinical manifestation, endoscopy finding and
      serological testing.

PMID- 25765029
TI  - [Fluorescence in-situ hybridization as a diagnostic tool for cutaneous melanoma].
AB  - OBJECTIVE: To explore the utility of fluorescence in situ hybridization as a
      diagnostic tool for cutaneous melanoma. METHODS: Twenty cutaneous melanomas and
      20 cutaneous nevi from pathology files were selected and analyzed by Vysis
      melanoma FISH probe kit targeting 3 loci on chromosome 6 (MYB, CEP6 and RREB1)
      and 1 locus on 11q (CCND1) and data were interpreted based on the Abbott criteria
      provided by the kit. RESULTS: Informative FISH results were obtained in 16
      melanomas and 18 nevi. Chromosomal aberrations were detected in 12 of the 16
      melanomas and only 1 of 18 nevi. CONCLUSION: FISH is a useful diagnostic tool and
      able to distinguish cutaneous nevus from melanoma with good sensitivity and
      specificity.

PMID- 25765030
TI  - [Re-evaluation of HER2 status in 1 501 invasive breast cancers according to the
      2013 American Society of Clinical Oncology/College of American Pathology
      guidelines].
AB  - OBJECTIVE: To retrospectively evaluate the HER2 status of 1 501 invasive breast
      cancer (IBC) by immunohistochemistry (IHC) and fluorescent in situ hybridizaion
      (FISH), and to compare and analyze the changes and their effects, using the 2007
      and 2013 American Society of Clinical Oncology/College of American
      Pathologist(ASCO/CAP) HER2 testing guidelines. METHODS: Tissue handling and HER2
      testing were performed according the 2007 ASCO/CAP guideline recommendations. The
      HER2 status of all newly diagnosed IBC were routinely assessed by IHC, and reflex
      FISH assay was done on all the IHC equivocal (IHC 2+) cases. The HER2 status of 1
      501 cases of IBC was re-evaluated according to these two criteria. RESULTS: Using
      the 2007 and 2013 ASCO/CAP criteria, the overall positive, equivocal and negative
      rates of HER2 over-expression and/or amplification in the 1 501 IBCs were 23.05%
      and 23.52%, 11.59% and 12.52%, and 65.36% and 63.96%, respectively. The positive
      and equivocal rates increased by 0.47% and 0.93% respectively, but the negative
      rate decreased by 1.40% when using the new criteria. For HER2 IHC staining using
      the 2007 and 2013 guidelines, the positive, equivocal and negative rates were
      17.99% and 18.13% (+0.13%), 32.51% and 32.91% (+0.40%) and 49.50% and 48, 97% (
      0.53%), respectively. FISH for HER2 amplification was done in 348 of the 1 501
      IBCs, and using the 2007 and 2013 guidelines, the positive, equivocal and
      negative rates were 27.59% and 29.02% (+1.43%), 1.15% and 3.74% (+2.59%) and
      71.26% and 67.24% (-4.02%), respectively. CONCLUSIONS: The application of 2013
      ASCO/CAP guideline could lead to an increase in positive and equivocal rates, and
      a decrease in negative rate. The influence could be more prominent for the
      evaluation of FISH result, and would raise the positive and equivocal rates since
      a mean HER2 copy number is used in the new criteria. Our re-estimation of IHC
      result was concordant with the prediction of the guideline.

PMID- 25765031
TI  - [Evaluation of immunohistochemistry HER2 results interpretation in invasive
      micropapillary carcinoma of the breast].
AB  - OBJECTIVE: To evaluate the standards of HER2 immunohistochemistry (IHC)
      interpretation in invasive micropapillary carcinoma of the breast (IMPC).
      METHODS: HER2 expression in 60 cases of IMPC was evaluated by IHC and
      fluorescence in situ hybridization (FISH) using TMA-based techniques. The
      characteristics between cases with HER2 IHC and HER2 gene amplification results
      were compared. RESULTS: Using 2007 American Society of Clinical Oncology/College
      of American Pathologist (ASCO/CAP) criteria, among the 52 cases that were
      successfully stained by IHC, 40 were HER2 IHC negative and 12 were equivocal
      (2+). Fifteen cases of HER2 IHC 0 were negative for amplification by FISH. Twenty
      five cases with IHC 1+ were tested by FISH; and of these, one showed HER2
      amplification, 2 were equivocal, and the others were not amplified. All cases of
      IHC 2+ showed HER2 amplification by FISH. IHC staining of HER2 was located at
      cell-cell membrane or basolateral membrane of micropapillary structure, but not
      in the cytoplasmic membrane facing the stroma in all 13 cases which were HER2
      amplified, including 12 showing very strong staining and one showing moderate
      staining. Among the 37 non amplified HER2 cases, 22 showed IHC staining at cell
      cell membrane or basolateral membrane (including 15 weak staining and 7 moderate
      staining). CONCLUSIONS: HER2 IHC detection in IMPC is characterized by staining
      at cell-cell membrane or basolateral membrane of the micropapillary structure,
      and absence of staining in the cytoplasmic membrane. It is suggested that
      interpretation of HER2 IHC staining should be based on membrane staining
      intensity, but not the completeness of the membrane staining in IMPC. It is
      suggested to determine the HER2 gene amplification status by using FISH when IHC
      staining shows moderate or strong intensity.

PMID- 25765032
TI  - [Pathologic diagnosis of hyalinizing clear cell carcinoma of salivary gland].

PMID- 25765033
TI  - [Implementation of standard operation procedures for KRAS andBRAF gene mutation
      detection in colorectal cancer].

PMID- 25765034
TI  - [Langerhans cell histiocytosis with diffuse involvement of intestinal
      tract:report of a case].

PMID- 25765035
TI  - [Plexiform angiomyxoid myofibroblastic tumor of stomach: report of a case].

PMID- 25765036
TI  - [Primary embryonal rhabdomyosarcoma of central nervous system: report of a case].

PMID- 25765037
TI  - [Papillary thyroid carcinoma with prominent hobnailing: report of a case].

PMID- 25765038
TI  - [Diagnostic challenges of Ewing sarcoma-like small round blue cell tumors: an
      update].

PMID- 25765039
TI  - [Clinicopathologic updates on gastrointestinal stromal tumor].

PMID- 25765040
TI  - [Human papilloma virus negative cervical cancer].

PMID- 25765041
TI  - [Research progress in autophagy and lymphoma].

PMID- 25765042
TI  - The genome sequence of Pseudoplusia includens single nucleopolyhedrovirus and an
      analysis of p26 gene evolution in the baculoviruses.
AB  - BACKGROUND: Pseudoplusia includens single nucleopolyhedrovirus (PsinSNPV-IE) is a
      baculovirus recently identified in our laboratory, with high pathogenicity to the
      soybean looper, Chrysodeixis includens (Lepidoptera: Noctuidae) (Walker, 1858).
      In Brazil, the C. includens caterpillar is an emerging pest and has caused
      significant losses in soybean and cotton crops. The PsinSNPV genome was
      determined and the phylogeny of the p26 gene within the family Baculoviridae was
      investigated. RESULTS: The complete genome of PsinSNPV was sequenced (Roche 454
      GS FLX - Titanium platform), annotated and compared with other
      Alphabaculoviruses, displaying a genome apparently different from other
      baculoviruses so far sequenced. The circular double-stranded DNA genome is
      139,132 bp in length, with a GC content of 39.3 % and contains 141 open reading
      frames (ORFs). PsinSNPV possesses the 37 conserved baculovirus core genes, 102
      genes found in other baculoviruses and 2 unique ORFs. Two baculovirus repeat ORFs
      (bro) homologs, bro-a (Psin33) and bro-b (Psin69), were identified and compared
      with Chrysodeixis chalcites nucleopolyhedrovirus (ChchNPV) and Trichoplusia ni
      single nucleopolyhedrovirus (TnSNPV) bro genes and showed high similarity,
      suggesting that these genes may be derived from an ancestor common to these
      viruses. The homologous repeats (hrs) are absent from the PsinSNPV genome, which
      is also the case in ChchNPV and TnSNPV. Two p26 gene homologs (p26a and p26b)
      were found in the PsinSNPV genome. P26 is thought to be required for optimal
      virion occlusion in the occlusion bodies (OBs), but its function is not well
      characterized. The P26 phylogenetic tree suggests that this gene was obtained
      from three independent acquisition events within the Baculoviridae family. The
      presence of a signal peptide only in the PsinSNPV p26a/ORF-20 homolog indicates
      distinct function between the two P26 proteins. CONCLUSIONS: PsinSNPV has a
      genomic sequence apparently different from other baculoviruses sequenced so far.
      The complete genome sequence of PsinSNPV will provide a valuable resource,
      contributing to studies on its molecular biology and functional genomics, and
      will promote the development of this virus as an effective bioinsecticide.

PMID- 25765043
TI  - Greater occipital nerve blockade for the treatment of chronic migraine: a
      randomized, multicenter, double-blind, and placebo-controlled study.
AB  - OBJECTIVES: We aimed to assess the efficacy of greater occipital nerve (GON)
      blockade at chronic migraine (CM) treatment. MATERIALS AND METHODS: Patients with
      CM were randomly divided into two groups of 42. GON blockade was administered
      four times (once per week) with saline in group A or bupivacaine in group B.
      After 4 weeks of treatment, blinding was removed; in group A, GON blockade was
      achieved using bupivacaine, while group B continued to receive bupivacaine, and
      blockade was administered once per month, then followed for 2 months. Primary
      endpoint was the difference in number of headache days, duration of headache, and
      pain scores. RESULTS: Seventy-two of 84 patients completed the study. After 1
      month of treatment, number of headache days had decreased from 16.9 +/- 5.7 to
      13.2 +/- 6.7 in group A (P = 0.035) and from 18.1 +/- 5.3 to 8.8 +/- 4.8 in group
      B (P < 0.001), (P = 0.004, between groups); duration of headache (hour) had
      decreased from 24.2 +/- 13.7 to 21.2 +/- 13.4 in group A (P = 0.223) and from
      25.9 +/- 16.3 to 19.3 +/- 11.5 in group B (P < 0.001), (P = 0.767, between
      groups). VAS score decreased from 8.1 +/- 0.9 to 6.7 +/- 1.6 in group A (P =
      0.002) and from 8.4 +/- 1.5 to 5.3 +/- 2.1 in group B (P < 0.001), (P = 0.004,
      between groups). After blinding was removed (in 2nd and 3rd month), group A
      exhibited similar results like group B in 3rd month. CONCLUSIONS: Our results
      suggest that GON blockade with bupivacaine was superior to placebo and was found
      to be effective, safe, and cost-effective for the treatment of CM. According to
      our knowledge, this is the first randomized, multicentre, double-blind, and
      placebo-controlled study in the literature in this field of work.

PMID- 25765044
TI  - Pseudogenes transcribed in breast invasive carcinoma show subtype-specific
      expression and ceRNA potential.
AB  - BACKGROUND: Recent studies have shown that some pseudogenes are transcribed and
      contribute to cancer when dysregulated. In particular, pseudogene transcripts can
      function as competing endogenous RNAs (ceRNAs). The high similarity of gene and
      pseudogene nucleotide sequence has hindered experimental investigation of these
      mechanisms using RNA-seq. Furthermore, previous studies of pseudogenes in breast
      cancer have not integrated miRNA expression data in order to perform large-scale
      analysis of ceRNA potential. Thus, knowledge of both pseudogene ceRNA function
      and the role of pseudogene expression in cancer are restricted to isolated
      examples. RESULTS: To investigate whether transcribed pseudogenes play a
      pervasive regulatory role in cancer, we developed a novel bioinformatic method
      for measuring pseudogene transcription from RNA-seq data. We applied this method
      to 819 breast cancer samples from The Cancer Genome Atlas (TCGA) project. We then
      clustered the samples using pseudogene expression levels and integrated sample
      paired pseudogene, gene and miRNA expression data with miRNA target prediction to
      determine whether more pseudogenes have ceRNA potential than expected by chance.
      CONCLUSIONS: Our analysis identifies with high confidence a set of 440
      pseudogenes that are transcribed in breast cancer tissue. Of this set, 309
      pseudogenes exhibit significant differential expression among breast cancer
      subtypes. Hierarchical clustering using only pseudogene expression levels
      accurately separates tumor samples from normal samples and discriminates the
      Basal subtype from the Luminal and Her2 subtypes. Correlation analysis shows more
      positively correlated pseudogene-parent gene pairs and negatively correlated
      pseudogene-miRNA pairs than expected by chance. Furthermore, 177 transcribed
      pseudogenes possess binding sites for co-expressed miRNAs that are also predicted
      to target their parent genes. Taken together, these results increase the catalog
      of putative pseudogene ceRNAs and suggest that pseudogene transcription in breast
      cancer may play a larger role than previously appreciated.

PMID- 25765045
TI  - Limitations of variable number of tandem repeat typing identified through whole
      genome sequencing of Mycobacterium avium subsp. paratuberculosis on a national
      and herd level.
AB  - BACKGROUND: Mycobacterium avium subsp. paratuberculosis (MAP), the causative
      bacterium of Johne's disease in dairy cattle, is widespread in the Canadian dairy
      industry and has significant economic and animal welfare implications. An
      understanding of the population dynamics of MAP can be used to identify
      introduction events, improve control efforts and target transmission pathways,
      although this requires an adequate understanding of MAP diversity and
      distribution between herds and across the country. Whole genome sequencing (WGS)
      offers a detailed assessment of the SNP-level diversity and genetic relationship
      of isolates, whereas several molecular typing techniques used to investigate the
      molecular epidemiology of MAP, such as variable number of tandem repeat (VNTR)
      typing, target relatively unstable repetitive elements in the genome that may be
      too unpredictable to draw accurate conclusions. The objective of this study was
      to evaluate the diversity of bovine MAP isolates in Canadian dairy herds using
      WGS and then determine if VNTR typing can distinguish truly related and unrelated
      isolates. RESULTS: Phylogenetic analysis based on 3,039 SNPs identified through
      WGS of 124 MAP isolates identified eight genetically distinct subtypes in dairy
      herds from seven Canadian provinces, with the dominant type including over 80% of
      MAP isolates. VNTR typing of 527 MAP isolates identified 12 types, including
      "bison type" isolates, from seven different herds. At a national level, MAP
      isolates differed from each other by 1-2 to 239-240 SNPs, regardless of whether
      they belonged to the same or different VNTR types. A herd-level analysis of MAP
      isolates demonstrated that VNTR typing may both over-estimate and under-estimate
      the relatedness of MAP isolates found within a single herd. CONCLUSIONS: The
      presence of multiple MAP subtypes in Canada suggests multiple introductions into
      the country including what has now become one dominant type, an important finding
      for Johne's disease control. VNTR typing often failed to identify closely and
      distantly related isolates, limiting the applicability of using this typing
      scheme to study the molecular epidemiology of MAP at a national and herd-level.

PMID- 25765046
TI  - Precisely mapping a major gene conferring resistance to Hessian fly in bread
      wheat using genotyping-by-sequencing.
AB  - BACKGROUND: One of the reasons hard red winter wheat cultivar 'Duster' (PI
      644016) is widely grown in the southern Great Plains is that it confers a
      consistently high level of resistance to biotype GP of Hessian fly (Hf). However,
      little is known about the genetic mechanism underlying Hf resistance in Duster.
      This study aimed to unravel complex structures of the Hf region on chromosome 1AS
      in wheat by using genotyping-by-sequencing (GBS) markers and single nucleotide
      polymorphism (SNP) markers. RESULTS: Doubled haploid (DH) lines generated from a
      cross between two winter wheat cultivars, 'Duster' and 'Billings' , were used to
      identify genes in Duster responsible for effective and consistent resistance to
      Hf. Segregation in reaction of the 282 DH lines to Hf biotype GP fit a one-gene
      model. The DH population was genotyped using 2,358 markers developed using the
      GBS approach. A major QTL, explaining 88% of the total phenotypic variation, was
      mapped to a chromosome region that spanned 178 cM and contained 205 GBS markers
      plus 1 SSR marker and 1 gene marker, with 0.86 cM per marker in genetic distance.
      The analyses of GBS marker sequences and further mapping of SSR and gene markers
      enabled location of the QTL-containing linkage group on the short arm of
      chromosome 1A. Comparative mapping of the common markers for the gene for QHf.osu
      1A (d) in Duster and the Hf-resistance gene for QHf.osu-1A (74) in cultivar
      '2174' showed that the two Hf resistance genes are located on the same chromosome
      arm 1AS, only 11.2 cM apart in genetic distance. The gene at QHf.osu-1A (d) in
      Duster has been delimited within a 2.7 cM region. CONCLUSION: Two distinct
      resistance genes exist on the short arm of chromosome 1A as found in the two hard
      red winter cultivars, 2174 and Duster. Whereas the Hf resistance gene in 2174 is
      likely allelic to one or more of the previously mapped resistance genes (H9, H10,
      H11, H16, or H17) in wheat, the gene in Duster is novel and confers a more
      consistent phenotype than 2174 in response to biotype GP infestation in
      controlled-environment assays.

PMID- 25765048
TI  - The complex role of having confidant on the development of Alzheimer's disease in
      a community-based cohort of older people in Brazil.
AB  - BACKGROUND: Social interaction is a lifestyle factor associated with a decreased
      risk of dementia in several studies. However, specific aspects of these social
      factors influencing dementia are unknown. This study aimed at evaluating the role
      of the distinct aspects of social support on the incidence of dementia in a
      community-based cohort of older people in Brazil. METHODS: A total of 345 healthy
      and independent elderly subjects living in the community were followed by 12
      years. Incident cases of dementia and probable Alzheimer's disease were defined
      by DSM-IV criteria and NINCDS-ADRDA criteria, respectively. Social variables
      evaluated were marital status, living arrangement, living children, living
      sibling, confidant and attending recreational groups. Sex, age, education, Mini
      Mental State Examination (MMSE) score, depressive symptoms and family income were
      entered as co-variates in a Cox proportional hazard model. RESULTS: The absence
      of confidant was the only social variable associated to higher risk of developing
      dementia (HR = 5.31; p < 0.001), even after adjustment for age (HR = 1.08; p =
      0.048) and baseline MMSE score (HR = 0.79; p = 0.002). CONCLUSIONS: Our data
      suggest that to have a confidant could be an important lifestyle factor
      associated with dementia.

PMID- 25765047
TI  - Serial plasma metabolites following hypoxic-ischemic encephalopathy in a nonhuman
      primate model.
AB  - Biomarkers that indicate the severity of hypoxic-ischemic brain injury and
      response to treatment and that predict neurodevelopmental outcomes are urgently
      needed to improve the care of affected neonates. We hypothesize that sequentially
      obtained plasma metabolomes will provide indicators of brain injury and repair,
      allowing for the prediction of neurodevelopmental outcomes. A total of 33 Macaca
      nemestrina underwent 0, 15 or 18 min of in utero umbilical cord occlusion (UCO)
      to induce hypoxic-ischemic encephalopathy and were then delivered by hysterotomy,
      resuscitated and stabilized. Serial blood samples were obtained at baseline (cord
      blood) and at 0.1, 24, 48, and 72 h of age. Treatment groups included
      nonasphyxiated controls (n = 7), untreated UCO (n = 11), UCO + hypothermia (HT; n
      = 6), and UCO + HT + erythropoietin (n = 9). Metabolites were extracted and
      analyzed using comprehensive two-dimensional gas chromatography coupled with time
      of-flight mass spectrometry and quantified by PARAFAC (parallel factor analysis).
      Using nontargeted discovery-based methods, we identified 63 metabolites as
      potential biomarkers. The changes in metabolite concentrations were characterized
      and compared between treatment groups. Further comparison determined that 8
      metabolites (arachidonic acid, butanoic acid, citric acid, fumaric acid, lactate,
      malate, propanoic acid, and succinic acid) correlated with early and/or long-term
      neurodevelopmental outcomes. The combined outcomes of death or cerebral palsy
      correlated with citric acid, fumaric acid, lactate, and propanoic acid. This
      change in circulating metabolome after UCO may reflect cellular metabolism and
      biochemical changes in response to the severity of brain injury and have
      potential to predict neurodevelopmental outcomes.

PMID- 25765050
TI  - Assessing risk factors for dental caries: a statistical modeling approach.
AB  - The problem of identifying potential determinants and predictors of dental caries
      is of key importance in caries research and it has received considerable
      attention in the scientific literature. From the methodological side, a broad
      range of statistical models is currently available to analyze dental caries
      indices (DMFT, dmfs, etc.). These models have been applied in several studies to
      investigate the impact of different risk factors on the cumulative severity of
      dental caries experience. However, in most of the cases (i) these studies focus
      on a very specific subset of risk factors; and (ii) in the statistical modeling
      only few candidate models are considered and model selection is at best only
      marginally addressed. As a result, our understanding of the robustness of the
      statistical inferences with respect to the choice of the model is very limited;
      the richness of the set of statistical models available for analysis in only
      marginally exploited; and inferences could be biased due the omission of
      potentially important confounding variables in the model's specification. In this
      paper we argue that these limitations can be overcome considering a general class
      of candidate models and carefully exploring the model space using standard model
      selection criteria and measures of global fit and predictive performance of the
      candidate models. Strengths and limitations of the proposed approach are
      illustrated with a real data set. In our illustration the model space contains
      more than 2.6 million models, which require inferences to be adjusted for
      'optimism'.

PMID- 25765049
TI  - Predicting functional and regulatory divergence of a drug resistance transporter
      gene in the human malaria parasite.
AB  - BACKGROUND: The paradigm of resistance evolution to chemotherapeutic agents is
      that a key coding mutation in a specific gene drives resistance to a particular
      drug. In the case of resistance to the anti-malarial drug chloroquine (CQ), a
      specific mutation in the transporter pfcrt is associated with resistance. Here,
      we apply a series of analytical steps to gene expression data from our lab and
      leverage 3 independent datasets to identify pfcrt-interacting genes. Resulting
      networks provide insights into pfcrt's biological functions and regulation, as
      well as the divergent phenotypic effects of its allelic variants in different
      genetic backgrounds. RESULTS: To identify pfcrt-interacting genes, we analyze
      pfcrt co-expression networks in 2 phenotypic states - CQ-resistant (CQR) and CQ
      sensitive (CQS) recombinant progeny clones - using a computational approach that
      prioritizes gene interactions into functional and regulatory relationships. For
      both phenotypic states, pfcrt co-expressed gene sets are associated with
      hemoglobin metabolism, consistent with CQ's expected mode of action. To predict
      the drivers of co-expression divergence, we integrate topological relationships
      in the co-expression networks with available high confidence protein-protein
      interaction data. This analysis identifies 3 transcriptional regulators from the
      ApiAP2 family and histone acetylation as potential mediators of these
      divergences. We validate the predicted divergences in DNA mismatch repair and
      histone acetylation by measuring the effects of small molecule inhibitors in
      recombinant progeny clones combined with quantitative trait locus (QTL) mapping.
      CONCLUSIONS: This work demonstrates the utility of differential co-expression
      viewed in a network framework to uncover functional and regulatory divergence in
      phenotypically distinct parasites. pfcrt-associated co-expression in the CQ
      resistant progeny highlights CQR-specific gene relationships and possible
      targeted intervention strategies. The approaches outlined here can be readily
      generalized to other parasite populations and drug resistances.

PMID- 25765052
TI  - Spin currents and filtering behavior in zigzag graphene nanoribbons with adsorbed
      molybdenum chains.
AB  - By means of density-functional-theoretic calculations, we investigated the
      structural, electronic and transport properties of hydrogen-passivated zigzag
      graphene nanoribbons (ZGNRs) on which a one-atom-thick Mo chain was adsorbed
      (with or without one or two missing atoms), or in which the passivating hydrogen
      atoms were replaced by Mo atoms. Mo-passivated ZGNRs proved to be nonmagnetic.
      ZGNRs with an adsorbed defect-free Mo chain were most stable with the Mo atoms
      forming dimers above edge bay sites, which suppressed the magnetic moments of the
      C atoms in that half of the ribbon; around the Fermi level of these systems, each
      spin component had a transmission channel via the Mo spz band and one had an
      additional channel created by polarization of the ZGNR pi* band, leading to a net
      spin current. The absence of an Mo dimer from an Mo chain adsorbed at the ZGNR
      edge made the system a perfect spin filter at low voltage bias by suppressing the
      Mo spz band channels. Thus this last kind of hybrid system is a potential spin
      valve.

PMID- 25765051
TI  - The role of rare variants in systolic blood pressure: analysis of ExomeChip data
      in HyperGEN African Americans.
AB  - Cardiovascular diseases are among the most significant health problems in the
      United States today, with their major risk factor, hypertension,
      disproportionately affecting African Americans (AAs). Although GWAS have
      identified dozens of common variants associated with blood pressure (BP) and
      hypertension in European Americans, these variants collectively explain <2.5% of
      BP variance, and most of the genetic variants remain yet to be identified. Here,
      we report the results from rare-variant analysis of systolic BP using 94,595 rare
      and low-frequency variants (minor allele frequency, MAF, <5%) from the Illumina
      exome array genotyped in 2,045 HyperGEN AAs. In addition to single-variant
      analysis, 4 gene-level association tests were used for analysis: burden and
      family-based SKAT tests using MAF cutoffs of 1 and 5%. The gene-based methods
      often provided lower p values than the single-variant approach. Some consistency
      was observed across these 4 gene-based analysis options. While neither the gene
      based analyses nor the single-variant analysis produced genome-wide significant
      results, the top signals, which had supporting evidence from multiple gene-based
      methods, were of borderline significance. Though additional molecular validations
      are required, 6 of the 16 most promising genes are biologically plausible with
      physiological connections to BP regulation.

PMID- 25765053
TI  - Diverse patterns of perilymphatic space enhancement in the rat inner ear after
      intratympanic injection of two different types of gadolinium: a 9.4-tesla
      magnetic resonance study.
AB  - OBJECTIVE: To compare the quality of perilymphatic enhancement in the rat inner
      ear after intratympanic injection of two types of gadolinium with a 9.4-tesla
      micro-MRI. MATERIALS AND METHODS: Gadolinium was injected into the middle ear in
      6 Sprague-Dawley rats via the transtympanic route. The left ear was injected with
      Gd-DO3A-butrol first, and then the right ear was injected with Gd-DOTA. MR images
      of the inner ear were acquired 1.0, 1.5, 2.0, 2.5, 3.0, 3.5, and 4 h after
      intratympanic (IT) injection using an Agilent MRI system 9.4T/160/AS. The
      normalized signal intensity was quantitatively analyzed at the scala vestibuli
      (SV), scala media, and scala tympani (ST) using a Marosis M-view system. Then the
      normalized signal intensities (SIs) were compared between the two contrast
      agents. RESULTS: For Gd-DO3A-butrol, the SI was as low as 1.0-1.5 throughout 1-4
      h at the SV and ST of the basal turn. The maximum SI was 1.5 +/- 0.5 at the SV (2
      h) and 1.3 +/- 0.5 at the ST (2 h). For Gd-DOTA, the 1-hour postinjection SI at
      the basal turn was 2.5 +/- 0.5 at the SV, 1.6 +/- 0.3 at the ST, and 1.2 +/- 0.3
      at the scala media. In the apical turn, the maximum SI was reached after 2.5 h.
      The maximum SI in the apical turn was 1.8 +/- 0.4 at the SV (3.5 h), 1.8 +/- 0.4
      at the ST (4 h), and 1.4 +/- 0.3 at the scala media (4 h). CONCLUSIONS: We were
      able to clearly visualize and separate the ST and SV using IT Gd and 9.4-tesla
      micro-MRI. We recommend using Gd-DO3A-butrol over Gd-DOTA and to perform the MRI
      2.5 h after using IT Gd in the rat inner ear.

PMID- 25765054
TI  - The Case Mix of Patients Presenting with Full-Thickness Macular Holes and
      Progression before Surgery: Implications for Optimum Management.
AB  - AIMS: Analysis of pre-operative spectral domain optical coherence tomography (SD
      OCT) characteristics of full-thickness macular holes (FTMH) and effect on optimum
      management. METHODS: We retrospectively reviewed SD-OCT characteristics of a
      consecutive cohort of patients waitlisted for FTMH surgery and categorized them
      by current evidence-based treatments. RESULTS: Out of the 106 holes analysed, 36
      were small, 40 medium and 30 large. Initially, 33 holes had vitreomacular
      adhesion (VMA). 41 holes were analysed for change in characteristics with a
      median duration of 8 weeks between the scans. The number of small or medium holes
      decreased from 20 to 6 and that of large holes doubled. The number of holes with
      VMA halved. Smaller hole size (p = 0.014) and being phakic (p = 0.048) were
      associated with a larger increase in size. The strongest predictor of hole
      progression into a different surgical management category was the presence of
      VMA. CONCLUSION: FTMH characteristics can change significantly pre-operatively
      and affect optimal treatment choice.

PMID- 25765055
TI  - Low bilirubin levels are associated with coronary slow flow phenomenon.
AB  - BACKGROUND AND AIM: Increasing evidence suggests an inverse relationship between
      bilirubin levels and cardiovascular disease. The present study evaluated the
      effect of bilirubin level on the slow coronary flow (SCF) phenomenon. METHODS:
      This study was cross-sectional and observational. We enrolled 222 consecutive
      patients who underwent coronary angiography for suspected ischaemic heart disease
      and were found to have normal or near-normal coronary arteries. Then, bilirubin
      levels were measured and coronary flow rate was assessed using the thrombolysis
      in myocardial infarction (TIMI) frame count. SCF was defined as a TIMI frame
      count > 27 frames. RESULTS: SCF was observed in at least one coronary vessel in
      22 of the 222 subjects, indicating a prevalence of 10%. Serum bilirubin levels
      were significantly decreased in the SCF group. In multivariate logistic
      regression analysis, total bilirubin and diabetes mellitus were independent risk
      factors for SCF. Furthermore, after adjusting for age, sex, and cardiovascular
      disease risk factors, serum bilirubin level (B = -0.34, p < 0.001) was
      independently associated with TIMI frame count. CONCLUSIONS: These findings
      suggest that serum total bilirubin levels may be a useful marker for patients
      with the SCF phenomenon. We believe that further studies are needed to clarify
      the role of bilirubin in patients with SCF.

PMID- 25765056
TI  - How aggressively should we treat short stature?

PMID- 25765058
TI  - Civilian protection, environmental pollution and conflict - a role for the public
      health community.

PMID- 25765057
TI  - Impact of karyotype organization on interlocus recombination between T cell
      receptor genes in Equidae.
AB  - The T cell receptor (TCR) genes (TRA, TRB, TRD and TRG) reside in 3 different
      chromosomal regions. During the maturation of T lymphocytes, the TCR genes are
      rearranged by site-specific recombination, a process that also predisposes T
      cells to aberrant rearrangements. Illegitimate recombination between the TCR
      genes occurs at a low level in healthy individuals, but this frequency may
      correlate with the risk of lymphoma. The aim of this work was to investigate
      interlocus recombination in equids. Illegitimate rearrangements were studied in
      peripheral blood lymphocytes by FISH with painting and BAC probes and by
      sequencing of PCR products, and the frequencies of recombination were assessed in
      horses and 4 other equids. The presence of several trans-rearrangement products
      between the TRA and TRG genes was verified by PCR in all investigated equids.
      Frequencies of trans-rearrangements in horses are higher than in humans, and
      colocalization of the TCR genes on the same chromosome increases the incidence of
      trans-rearrangements between them. The orientation of the TCR genes does not
      impact interlocus recombination itself but does affect the viability of cells
      carrying its products and consequently the number of trans-rearrangements
      observed in lymphocytes.

PMID- 25765059
TI  - Beyond Guidelines: Effectiveness of a Programme in Achieving Operative
      Laparoscopy for all Women Requiring Surgical Management of Ectopic Pregnancy.
AB  - BACKGROUND/AIMS: Operative laparoscopy (OL) is considered the gold standard
      surgical treatment of ectopic pregnancy (EP). We questioned whether a training
      programme to foster OL treatment is able to ensure that all women needing
      surgical management are treated by OL irrespective of the site of EP,
      haemodynamic status and clinical complexity. METHODS: A 13-year cohort study of
      963 women who underwent surgical management was conducted. We instituted a
      'universal OL' programme in 2003 for the management of all the types of EP
      irrespective of the haemodynamic status. RESULTS: There were 802 women in the
      prospective (2003-2013) and 161 in the retrospective arm (2000-2002). The rate of
      OL before 2003 was 34%. During the year of programme implementation, the OL rate
      rose from 89% in 2003 to 96% in 2004. It took 4 years to achieve a 100% OL rate
      in haemodynamically stable patients. In 2013, we were able to achieve OL
      treatment for all patients irrespective of haemodynamic status, the complexity of
      surgery or the location of EP. CONCLUSION: Our study demonstrates that a
      dedicated team with special training in minimal invasive surgery can improve
      surgical management of all categories of EPs, and this goal should be achievable
      across most units.

PMID- 25765061
TI  - Catunarosides I-L, four new triterpenoid saponins from the stem bark of
      Catunaregam spinosa.
AB  - Four new triterpenoid saponins, Catunaroside I [3-O-beta-D-glucopyranosyl-(1->3)
      beta-D-glucopyranosyl-arjunic acid 28-O-beta-D-glucopyranoside] (1), Catunaroside
      J [3-O-beta-D-glucopyranosyl-(1->2)-[beta-D-glucopyranosyl-(1->3)]-beta-D
      glucopyranosyl-arjunic acid 28-O-beta-D-glucopyranoside] (2), Catunaroside K [3-O
      beta-D-glucopyranosyl-(1->2)-[beta-D-glucopyranosyl-(1->3)]-beta-D-glucopyranosyl
      tormentic acid] (3), and Catunaroside L [3-O-beta-D-glucopyranosyl-(1->2)-[beta-D
      glucopyranosyl-(1->3)]-beta-D-glucopyranosyl-pomolic acid] (4), and two known
      triterpenoid saponin Arjunetoside (5) and Randiasaponin VII (6), were isolated
      from the stem bark of Catunaregam spinosa. Their structures were elucidated on
      the basis of their spectral data and chemical evidence. 

PMID- 25765060
TI  - Effect of neutral pH and low-glucose degradation product-containing peritoneal
      dialysis solution on residual renal function in peritoneal dialysis patients: a
      meta-analysis.
AB  - BACKGROUND: Glucose degradation products (GDPs) in peritoneal dialysis (PD)
      solution (PDS) have been shown to inflict damage to the kidney, which is the
      major organ for advanced glycosylation end product elimination. Hence, this study
      investigated whether new PDSs with neutral pH and low-GDPs have a beneficial
      effect on the preservation of residual renal function (RRF) among PD patients.
      METHODS: Randomized controlled trials examining the effect of neutral pH and low
      GDP PDSs on RRF in PD patients >18 years old compared with conventional PDSs were
      selected. The modality of PD treatment was continuous ambulatory PD. The primary
      outcome variable was mean RRF value. Weekly Kt/V, urine volume, peritoneal
      ultrafiltration, blood pressure and all-cause mortality of PD patients were
      measured as secondary outcome variables. RESULTS: We identified 6 randomized
      controlled trials and found that patients using low-GDP PDSs had a much slower
      rate of RRF loss compared with patients using conventional PDSs [mean difference
      (MD) = 0.45, 95% confidence intervals (CI) 0.10-0.80, p = 0.01]. In addition,
      weekly Kt/V was markedly improved in the low-GDP PDS group (MD = 0.13, 95% CI
      0.06-0.21, p = 0.0005), and urine volume was increased (MD = 110.34, 95% CI 8.58
      212.10, p = 0.03). No significant differences were observed between the two
      groups with respect to peritoneal ultrafiltration, blood pressure and risk of all
      cause mortality. CONCLUSION: Our meta-analysis demonstrates a significant benefit
      of using low-GDP PDSs for RRF preservation in PD patients. Further trials are
      needed to determine whether this beneficial effect can affect long-term clinical
      outcomes.

PMID- 25765062
TI  - Quantifying hummingbird preference for floral trait combinations: The role of
      selection on trait interactions in the evolution of pollination syndromes.
AB  - Darwin recognized the flower's importance for the study of adaptation and
      emphasized that the flower's functionality reflects the coordinated action of
      multiple traits. Here we use a multitrait manipulative approach to quantify the
      potential role of selection acting on floral trait combinations underlying the
      divergence and maintenance of three related North American species of Silene
      (Caryophyllaceae). We artificially generated 48 plant phenotypes corresponding to
      all combinations of key attractive traits differing among the three Silene
      species (color, height, inflorescence architecture, flower orientation, and
      corolla-tube width). We quantified main and interaction effects of trait
      manipulation on hummingbird visitation preference using experimental arrays. The
      main effects of floral display height and floral orientation strongly influenced
      hummingbird visitation, with hummingbirds preferring flowers held high above the
      ground and vertically to the sky. Hummingbirds also prefer traits in a
      nonadditive manner as multiple two-way and higher order interaction effects were
      important predictors of hummingbird visitation. Contemporary trait combinations
      found in hummingbird pollinated S. virginica are mostly preferred. Our study
      demonstrates the likelihood of pollination syndromes evolving due to selection on
      trait combinations and highlights the importance of trait interactions in
      understanding the evolution of complex adaptations.

PMID- 25765063
TI  - Quantitative Electroencephalographic Analysis in Patients with Chronic Hepatitis
      C Treated with Interferon-alpha: A Review Article.
AB  - This review article describes our results regarding the relationship between
      quantitative electroencephalographic (qEEG) changes and the administration of
      interferon (IFN) alpha. We prospectively and blindly assessed a serial cohort of
      chronic hepatitis C patients. A total of 168 consecutive patients with chronic
      hepatitis C were enrolled from 1995 to 2007. IFNalpha was administered
      intramuscularly at 9 * 106 IU daily for the first 4 weeks and then three times a
      week for the next 20 weeks. Consecutive EEGs obtained before, 2 and 4 weeks after
      treatment initiation, and 2-3 days after treatment termination were assessed. EEG
      recordings were obtained from each patient in the resting awake condition with
      their eyes closed. The absolute power for each frequency band was determined
      using qEEG techniques. Diffuse slowing was observed during IFNalpha treatment and
      was reversible after completion of treatment. A tendency to this qEEG change was
      generally observed in all patients. The patient's age and severity of chronic
      hepatitis were factors that influenced qEEG changes during IFNalpha treatment.
      The change in the Mini-Mental State Examination score and IFNalpha-induced
      depression were also related to qEEG changes. Such diffuse EEG changes indicated
      mild encephalopathy associated with IFNalpha treatment. (c) 2015 S. Karger AG,
      Basel.

PMID- 25765064
TI  - Development of Autoimmune-Mediated beta Cell Failure After Total Pancreatectomy
      With Autologous Islet Transplantation.
AB  - Total pancreatectomy with islet autotransplantation (TPIAT) is performed for
      definitive treatment of chronic pancreatitis; patients are not diabetic before
      surgery, or have C-peptide positive pancreatogenous diabetes. Thus, TPIAT
      recipients are not traditionally considered at risk for autoimmune loss of the
      islet graft. We describe a 43-year-old female who underwent TPIAT with high mass
      islet graft of 6031 IEQ/kg, with no evidence of presurgical beta cell
      autoimmunity who developed type 1 diabetes within the first year after TPIAT,
      resulting in complete loss of beta cell function. The patient had positive GAD
      and insulin autoantibodies at 1 year and 18 months after TPIAT, not present
      prior, and undetectable C-peptide after mixed meal and intravenous glucose
      tolerance testing at 18 months. Glucagon secretion was preserved, suggesting the
      transplanted alpha cell mass was intact. HLA typing revealed a DR3/DR4 class II
      haplotype. This case highlights the need to consider de novo type 1 diabetes in
      patients with unexpected islet graft failure after TPIAT.

PMID- 25765065
TI  - The role of Schwann cell-axon interaction in peripheral nerve regeneration.
AB  - After peripheral nerve injury, Schwann cells are released from the degenerating
      nerve, dedifferentiated, and then actively participate in axonal regeneration.
      Dedifferentiated Schwann cells, together with macrophages, are involved in
      eliminating myelin debris, forming bands of Bungner that provide pathways for
      regenerating axons, and redifferentiating for remyelination. Activation of Erk1/2
      and c-Jun was shown to induce stepwise repair programs in Schwann cells,
      indicating that plastic changes in Schwann cell activity contribute to
      interaction with axons for regeneration. Schwann cell beta1 integrin was
      identified to mediate the Cdc2-vimentin pathway and further connect to adaptor
      molecules in the growth cone of regenerating axons through the binding of
      extracellular matrix (ECM) proteins. Timely interaction between Schwann cells and
      the axon (S-A) is critical to achieving efficient axonal regeneration because the
      delay in S-A interaction results in retarded nerve repair and chronic nerve
      damage. By comparing with the role of Schwann cells in developing nerves, this
      review is focused on cellular and molecular aspects of Schwann cell interaction
      with axons at the early stages of regeneration.

PMID- 25765067
TI  - Climate change. The weakening summer circulation in the Northern Hemisphere mid
      latitudes.
AB  - Rapid warming in the Arctic could influence mid-latitude circulation by reducing
      the poleward temperature gradient. The largest changes are generally expected in
      autumn or winter, but whether significant changes have occurred is debated. Here
      we report significant weakening of summer circulation detected in three key
      dynamical quantities: (i) the zonal-mean zonal wind, (ii) the eddy kinetic energy
      (EKE), and (iii) the amplitude of fast-moving Rossby waves. Weakening of the
      zonal wind is explained by a reduction in the poleward temperature gradient.
      Changes in Rossby waves and EKE are consistent with regression analyses of
      climate model projections and changes over the seasonal cycle. Monthly heat
      extremes are associated with low EKE, and thus the observed weakening might have
      contributed to more persistent heat waves in recent summers. 

PMID- 25765066
TI  - Axonal regeneration. Systemic administration of epothilone B promotes axon
      regeneration after spinal cord injury.
AB  - After central nervous system (CNS) injury, inhibitory factors in the lesion scar
      and poor axon growth potential prevent axon regeneration. Microtubule
      stabilization reduces scarring and promotes axon growth. However, the cellular
      mechanisms of this dual effect remain unclear. Here, delayed systemic
      administration of a blood-brain barrier-permeable microtubule-stabilizing drug,
      epothilone B (epoB), decreased scarring after rodent spinal cord injury (SCI) by
      abrogating polarization and directed migration of scar-forming fibroblasts.
      Conversely, epothilone B reactivated neuronal polarization by inducing concerted
      microtubule polymerization into the axon tip, which propelled axon growth through
      an inhibitory environment. Together, these drug-elicited effects promoted axon
      regeneration and improved motor function after SCI. With recent clinical
      approval, epothilones hold promise for clinical use after CNS injury. 

PMID- 25765068
TI  - Wireless magnetothermal deep brain stimulation.
AB  - Wireless deep brain stimulation of well-defined neuronal populations could
      facilitate the study of intact brain circuits and the treatment of neurological
      disorders. Here, we demonstrate minimally invasive and remote neural excitation
      through the activation of the heat-sensitive capsaicin receptor TRPV1 by magnetic
      nanoparticles. When exposed to alternating magnetic fields, the nanoparticles
      dissipate heat generated by hysteresis, triggering widespread and reversible
      firing of TRPV1(+) neurons. Wireless magnetothermal stimulation in the ventral
      tegmental area of mice evoked excitation in subpopulations of neurons in the
      targeted brain region and in structures receiving excitatory projections. The
      nanoparticles persisted in the brain for over a month, allowing for chronic
      stimulation without the need for implants and connectors. 

PMID- 25765069
TI  - Tribology. Mechanisms of antiwear tribofilm growth revealed in situ by single
      asperity sliding contacts.
AB  - Zinc dialkyldithiophosphates (ZDDPs) form antiwear tribofilms at sliding
      interfaces and are widely used as additives in automotive lubricants. The
      mechanisms governing the tribofilm growth are not well understood, which limits
      the development of replacements that offer better performance and are less likely
      to degrade automobile catalytic converters over time. Using atomic force
      microscopy in ZDDP-containing lubricant base stock at elevated temperatures, we
      monitored the growth and properties of the tribofilms in situ in well-defined
      single-asperity sliding nanocontacts. Surface-based nucleation, growth, and
      thickness saturation of patchy tribofilms were observed. The growth rate
      increased exponentially with either applied compressive stress or temperature,
      consistent with a thermally activated, stress-assisted reaction rate model.
      Although some models rely on the presence of iron to catalyze tribofilm growth,
      the films grew regardless of the presence of iron on either the tip or substrate,
      highlighting the critical role of stress and thermal activation. 

PMID- 25765071
TI  - Quantum versus classical annealing of Ising spin glasses.
AB  - Quantum annealers use quantum fluctuations to escape local minima and find low
      energy configurations of a physical system. Strong evidence for superiority of
      quantum annealing (QA) has come from comparing QA implemented through quantum
      Monte Carlo (QMC) simulations to classical annealing. Motivated by recent
      experiments, we revisit the question of when quantum speedup may be expected.
      Although a better scaling is seen for QA in two-dimensional Ising spin glasses,
      this advantage is due to time discretization artifacts and measurements that are
      not possible on a physical quantum annealer. Simulations in the physically
      relevant continuous time limit, on the other hand, do not show superiority. Our
      results imply that care must be taken when using QMC simulations to assess the
      potential for quantum speedup. 

PMID- 25765072
TI  - The CO2 concentrating mechanism and photosynthetic carbon assimilation in
      limiting CO2 : how Chlamydomonas works against the gradient.
AB  - The CO2 concentrating mechanism (CCM) represents an effective strategy for carbon
      acquisition that enables microalgae to survive and proliferate when the CO2
      concentration limits photosynthesis. The CCM improves photosynthetic performance
      by raising the CO2 concentration at the site of ribulose-1,5-bisphosphate
      carboxylase/oxygenase (Rubisco), simultaneously enhancing carbon fixation and
      suppressing photorespiration. Active inorganic carbon (Ci) uptake, Rubisco
      sequestration and interconversion between different Ci species catalyzed by
      carbonic anhydrases (CAs) are key components in the CCM, and an array of
      molecular regulatory elements is present to facilitate the sensing of CO2
      availability, to regulate the expression of the CCM and to coordinate interplay
      between photosynthetic carbon metabolism and other metabolic processes in
      response to limiting CO2 conditions. This review intends to integrate our current
      understanding of the eukaryotic algal CCM and its interaction with carbon
      assimilation, based largely on Chlamydomonas as a model, and to illustrate how
      Chlamydomonas acclimates to limiting CO2 conditions and how its CCM is regulated.

PMID- 25765070
TI  - Cancer immunology. Mutational landscape determines sensitivity to PD-1 blockade
      in non-small cell lung cancer.
AB  - Immune checkpoint inhibitors, which unleash a patient's own T cells to kill
      tumors, are revolutionizing cancer treatment. To unravel the genomic determinants
      of response to this therapy, we used whole-exome sequencing of non-small cell
      lung cancers treated with pembrolizumab, an antibody targeting programmed cell
      death-1 (PD-1). In two independent cohorts, higher nonsynonymous mutation burden
      in tumors was associated with improved objective response, durable clinical
      benefit, and progression-free survival. Efficacy also correlated with the
      molecular smoking signature, higher neoantigen burden, and DNA repair pathway
      mutations; each factor was also associated with mutation burden. In one
      responder, neoantigen-specific CD8+ T cell responses paralleled tumor regression,
      suggesting that anti-PD-1 therapy enhances neoantigen-specific T cell reactivity.
      Our results suggest that the genomic landscape of lung cancers shapes response to
      anti-PD-1 therapy. 

PMID- 25765073
TI  - Microbial signature lipid biomarker analysis - an approach that is still
      preferred, even amid various method modifications.
AB  - The lipid composition of microbial communities can indicate their response to
      changes in the surrounding environment induced by anthropogenic practices,
      chemical contamination or climatic conditions. A considerable number of
      analytical techniques exist for the examination of microbial lipids. This article
      reviews a selection of methods available for environmental samples as applied for
      lipid extraction, fractionation, derivatization and quantification. The
      discussion focuses on the origin of the standard methods, the different modified
      versions developed for investigation of microbial lipids, as well as the
      advantages and limitations of each. Current modifications to standard methods
      show a number of improvements for each of the different steps associated with
      analysis. The advantages and disadvantages of lipid analysis compared to other
      popular techniques are clarified. Accordingly, the preferential utilization of
      signature lipid biomarker analysis in current research is considered. It is clear
      from recent literature that this technique stays relevant - mainly for the
      variety of microbial properties that can be determined in a single analysis. 

PMID- 25765074
TI  - Arginine increases development of in vitro-produced porcine embryos and affects
      the protein arginine methyltransferase-dimethylarginine dimethylaminohydrolase
      nitric oxide axis.
AB  - Culture systems promote development at rates lower than the in vivo environment.
      Here, we evaluated the embryo's transcriptome to determine what the embryo needs
      during development. A previous mRNA sequencing endeavour found upregulation of
      solute carrier family 7 (cationic amino acid transporter, y+ system), member 1
      (SLC7A1), an arginine transporter, in in vitro- compared with in vivo-cultured
      embryos. In the present study, we added different concentrations of arginine to
      our culture medium to meet the needs of the porcine embryo. Increasing arginine
      from 0.12 to 1.69mM improved the number of embryos that developed to the
      blastocyst stage. These blastocysts also had more total nuclei compared with
      controls and, specifically, more trophectoderm nuclei. Embryos cultured in 1.69mM
      arginine had lower SLC7A1 levels and a higher abundance of messages involved with
      glycolysis (hexokinase 1, hexokinase 2 and glutamic pyruvate transaminase
      (alanine aminotransferase) 2) and decreased expression of genes involved with
      blocking the tricarboxylic acid cycle (pyruvate dehydrogenase kinase, isozyme 1)
      and the pentose phosphate pathway (transaldolase 1). Expression of the protein
      arginine methyltransferase (PRMT) genes PRMT1, PRMT3 and PRMT5 throughout
      development was not affected by arginine. However, the dimethylarginine
      dimethylaminohydrolase 1 (DDAH1) and DDAH2 message was found to be differentially
      regulated through development, and the DDAH2 protein was localised to the nuclei
      of blastocysts. Arginine has a positive effect on preimplantation development and
      may be affecting the nitric oxide-DDAH-PRMT axis. 

PMID- 25765075
TI  - RNA-seq analysis reveals the role of red light in resistance against Pseudomonas
      syringae pv. tomato DC3000 in tomato plants.
AB  - BACKGROUND: Plants attenuate their responses to a variety of bacterial and fungal
      pathogens, leading to higher incidences of pathogen infection at night. However,
      little is known about the molecular mechanism responsible for the light-induced
      defence response; transcriptome data would likely facilitate the elucidation of
      this mechanism. RESULTS: In this study, we observed diurnal changes in tomato
      resistance to Pseudomonas syringae pv. tomato DC3000 (Pto DC3000), with the
      greatest susceptibility before midnight. Nightly light treatment, particularly
      red light treatment, significantly enhanced the resistance; this effect was
      correlated with increased salicylic acid (SA) accumulation and defence-related
      gene transcription. RNA-seq analysis revealed that red light induced a set of
      circadian rhythm-related genes involved in the phytochrome and SA-regulated
      resistance response. The biosynthesis and signalling pathways of multiple plant
      hormones (auxin, SA, jasmonate, and ethylene) were co-ordinately regulated
      following Pto DC3000 infection and red light, and the SA pathway was most
      significantly affected by red light and Pto DC3000 infection. This result
      indicates that SA-mediated signalling pathways are involved in red light-induced
      resistance to pathogens. Importantly, silencing of nonexpressor of pathogensis
      related genes 1 (NPR1) partially compromised red light-induced resistance against
      Pto DC3000. Furthermore, sets of genes involved in redox homeostasis (respiratory
      burst oxidase homologue, RBOH; glutathione S-transferases, GSTs;
      glycosyltransferase, GTs), calcium (calmodulin, CAM; calmodulin-binding protein,
      CBP), and defence (polyphenol oxidase, PPO; nudix hydrolase1, NUDX1) as well as
      transcription factors (WRKY18, WRKY53, WRKY60, WRKY70) and cellulose synthase
      were differentially induced at the transcriptional level by red light in response
      to pathogen challenge. CONCLUSIONS: Taken together, our results suggest that
      there is a diurnal change in susceptibility to Pto DC3000 with greatest
      susceptibility in the evening. The red light induced-resistance to Pto DC3000 at
      night is associated with enhancement of the SA pathway, cellulose synthase, and
      reduced redox homeostasis.

PMID- 25765077
TI  - Sour sweets and acidic beverage consumption are risk indicators for dental
      erosion.
AB  - This study aimed to investigate the association between dental erosive wear and
      potential background, behavioural and dietary risk indicators and to assess
      whether there is a dose-response relationship between the level of acidic
      beverage consumption and dental erosive wear among adolescents. Of 846
      adolescents (aged 16-18 years) scheduled for dental recall examinations, 795
      (94%) accepted to participate. All participants completed a self-administered
      questionnaire regarding their background (gender and age), tooth-brushing
      frequency and dietary habits (the amount and frequency of acidic food and
      beverage consumption as well as the chosen method and manner of consuming acidic
      drinks). The association between the presence of erosive lesions and the possible
      risk indicators was assessed by logistic regression analyses. Of all participants
      examined, 37% had >=3 surfaces with dental erosions and were considered to be
      affected individuals. In the present study, multivariate logistic analyses
      revealed a significant association between the dental erosive wear and high
      consumption of sour sweets and sports drinks. The tooth-brushing frequency was
      not significantly associated with dental erosive wear. Additionally, to the best
      of our knowledge, the results are the first to indicate a dose-response
      relationship between the daily consumption of acidic drinks and dental erosive
      wear.

PMID- 25765076
TI  - Tissue-specific transcriptome assemblies of the marine medaka Oryzias melastigma
      and comparative analysis with the freshwater medaka Oryzias latipes.
AB  - BACKGROUND: The marine medaka Oryzias melastigma has been demonstrated as a novel
      model for marine ecotoxicological studies. However, the lack of genome and
      transcriptome reference has largely restricted the use of O. melastigma in the
      assessment of in vivo molecular responses to environmental stresses and the
      analysis of biological toxicity in the marine environment. Although O. melastigma
      is believed to be phylogenetically closely related to Oryzias latipes, the
      divergence between these two species is still largely unknown. Using Illumina
      high-throughput RNA sequencing followed by de novo assembly and comprehensive
      gene annotation, we provided transcriptomic resources for the brain, liver, ovary
      and testis of O. melastigma. We also investigated the possible extent of
      divergence between O. melastigma and O. latipes at the transcriptome level.
      RESULTS: More than 14,000 transcripts across brain, liver, ovary and testis in
      marine medaka were annotated, of which 5880 transcripts were orthologous between
      O. melastigma and O. latipes. Tissue-enriched genes were identified in O.
      melastigma, and Gene Ontology analysis demonstrated the functional specificity of
      the annotated genes in respective tissue. Lastly, the identification of marine
      medaka-enriched transcripts suggested the necessity of generating transcriptome
      dataset of O. melastigma. CONCLUSIONS: Orthologous transcripts between O.
      melastigma and O. latipes, tissue-enriched genes and O. melastigma-enriched
      transcripts were identified. Genome-wide expression studies of marine medaka
      require an assembled transcriptome, and this sequencing effort has generated a
      valuable resource of coding DNA for a non-model species. This transcriptome
      resource will aid future studies assessing in vivo molecular responses to
      environmental stresses and those analyzing biological toxicity in the marine
      environment.

PMID- 25765078
TI  - Life style and the prevention of dementia.

PMID- 25765080
TI  - The EIF4G1 gene and Parkinson's disease.
AB  - Variants in the EIF4G1 gene have been recently identified to be responsible for
      autosomal dominant PD (PARK18), but its role in the PD-related neurodegeneration
      is unclear. Several EIF4G1 mutation/variants were found to be associated with PD,
      and functional studies have suggested that these variants may impair the ability
      of cells to rapidly and dynamically respond to stress, thus probably
      participating in the development of PD, and these indicated that EIF4G1 variants
      may play an important role in pathogenicity of PD, although the frequency is low.
      Further studies involving large sample size of patients with PD from diverse
      populations, as well as studies of EIF4G1 expression and in scaffold function,
      are warranted. 

PMID- 25765079
TI  - Induced pluripotent stem cell-derived neuronal cells from a sporadic Alzheimer's
      disease donor as a model for investigating AD-associated gene regulatory
      networks.
AB  - BACKGROUND: Alzheimer's disease (AD) is a complex, irreversible neurodegenerative
      disorder. At present there are neither reliable markers to diagnose AD at an
      early stage nor therapy. To investigate underlying disease mechanisms, induced
      pluripotent stem cells (iPSCs) allow the generation of patient-derived neuronal
      cells in a dish. RESULTS: In this study, employing iPS technology, we derived and
      characterized iPSCs from dermal fibroblasts of an 82-year-old female patient
      affected by sporadic AD. The AD-iPSCs were differentiated into neuronal cells, in
      order to generate disease-specific protein association networks modeling the
      molecular pathology on the transcriptome level of AD, to analyse the reflection
      of the disease phenotype in gene expression in AD-iPS neuronal cells, in
      particular in the ubiquitin-proteasome system (UPS), and to address expression of
      typical AD proteins. We detected the expression of p-tau and GSK3B, a
      physiological kinase of tau, in neuronal cells derived from AD-iPSCs. Treatment
      of neuronal cells differentiated from AD-iPSCs with an inhibitor of gamma
      secretase resulted in the down-regulation of p-tau. Transcriptome analysis of AD
      iPS derived neuronal cells revealed significant changes in the expression of
      genes associated with AD and with the constitutive as well as the inducible
      subunits of the proteasome complex. The neuronal cells expressed numerous genes
      associated with sub-regions within the brain thus suggesting the usefulness of
      our in-vitro model. Moreover, an AD-related protein interaction network composed
      of APP and GSK3B among others could be generated using neuronal cells
      differentiated from two AD-iPS cell lines. CONCLUSIONS: Our study demonstrates
      how an iPSC-based model system could represent (i) a tool to study the underlying
      molecular basis of sporadic AD, (ii) a platform for drug screening and toxicology
      studies which might unveil novel therapeutic avenues for this debilitating
      neuronal disorder.

PMID- 25765082
TI  - Chronic Spinal Cord Stimulation in the Treatment of Cerebral and Spinal
      Spasticity.
AB  - OBJECTIVES: The aim of this investigation is to assess the effectiveness of
      spinal cord stimulation (SCS) in different groups of patients with spasticity of
      different origin. MATERIALS AND METHODS: A retrospective study of the use of the
      method of SCS in 71 patients. The patient population was divided into two groups:
      52 cerebral palsy (CP) cases and 19 patients diagnosed with spasticity caused by
      spinal injury. The mean age was 7.14 +/- 4.06 and 35.68 +/- 12.42 years,
      respectively. The CP group included 41 cases of paraparesis and 11 cases
      tetraparesis. One quadripolar electrode was implanted into the posterior epidural
      space at Th10-Th12 level and an implantable pulse generator (Itrel3, Medtronic)
      was placed in a standard fashion. We performed 3-5 stimulation sessions per day;
      each lasted 30 min. The stimulation parameters were as follows: rate 100-130 Hz,
      pulse width 120-300 ms, amplitude 1.5-4 V. The follow-up ranged from 2 to 9
      years. RESULTS: Decrease in muscle tone was observed in all cases in the group of
      patients with spinal spasticity: from 3.71 +/- 0.61 on the Ashworth scale before
      the operation to 2.26 +/- 0.56 after the operation (p < 0.001). In the group of
      cerebral spasticity a significant decrease in muscle tone was observed only in
      patients with spastic lower paraparesis: from 3.36 +/- 0.41 before the operation
      to 1.97 +/- 0.91 after the operation (p < 0.005). In patients with spastic
      tetraparesis we did not observe any significant change in muscle tone. In 8 cases
      we discontinued the therapy several years after the procedure due to improvement
      in spasticity: in the CP group in 7 cases and in 1 spinal spasticity case, where
      SCS systems were explanted. CONCLUSION: Chronic SCS may be a method of choice for
      patients with moderate spinal and cerebral spasticity with predominant spastic
      lower paraparesis. In patients with spastic tetraparesis SCS therapy did not
      prove to be effective. We encountered improvement of the spasticity and no need
      for further SCS therapy in a small group of patients (11%). This phenomenon
      requires further investigation. (c) 2015 S. Karger AG, Basel.

PMID- 25765081
TI  - RNA Seq analysis of the Eimeria tenella gametocyte transcriptome reveals clues
      about the molecular basis for sexual reproduction and oocyst biogenesis.
AB  - BACKGROUND: The protozoan Eimeria tenella is a common parasite of chickens,
      causing avian coccidiosis, a disease of on-going concern to agricultural
      industries. The high prevalence of E. tenella can be attributed to the resilient
      oocyst stage, which is transmitted between hosts in the environment. As in
      related Coccidia, development of the eimerian oocyst appears to be dependent on
      completion of the parasite's sexual cycle. RNA Seq transcriptome profiling offers
      insights into the mechanisms governing the biology of E. tenella sexual stages
      (gametocytes) and the potential to identify targets for blocking parasite
      transmission. RESULTS: Comparisons between the sequenced transcriptomes of E.
      tenella gametocytes and two asexual developmental stages, merozoites and
      sporozoites, revealed upregulated gametocyte transcription of 863 genes. Many of
      these genes code for proteins involved in coccidian sexual biology, such as
      oocyst wall biosynthesis and fertilisation, and some of these were characterised
      in more depth. Thus, macrogametocyte-specific expression and localisation was
      confirmed for two proteins destined for incorporation into the oocyst wall, as
      well as for a subtilisin protease and an oxidoreductase. Homologues of an oocyst
      wall protein and oxidoreductase were found in the related coccidian, Toxoplasma
      gondii, and shown to be macrogametocyte-specific. In addition, a microgametocyte
      gamete fusion protein, EtHAP2, was discovered. CONCLUSIONS: The need for novel
      vaccine candidates capable of controlling coccidiosis is rising and this panel of
      gametocyte targets represents an invaluable resource for development of future
      strategies to interrupt parasite transmission, not just in Eimeria but in other
      Coccidia, including Toxoplasma, where transmission blocking is a relatively
      unexplored strategy.

PMID- 25765083
TI  - Usefulness of noninvasive methods for the study of bronchial inflammation in the
      control of patients with asthma.
AB  - Bronchial asthma is one of the most prevalent respiratory conditions. Although it
      is defined as an inflammatory disease, the current guidelines for both diagnosis
      and follow-up of patients are based only on clinical and lung function
      parameters. Current research is focused on finding markers that can accurately
      predict future risk, and on assessing the ability of these markers to guide
      medical treatment and thus improve prognosis. The use of noninvasive methods to
      study airway inflammation is gaining increasing support. The study of eosinophils
      in induced sputum has proved useful for the diagnosis of asthma; however, its
      clinical implementation is complex. Some studies have shown that the measurement
      of exhaled nitric oxide (FeNO) may also be useful to establish disease phenotypes
      and improve control. Others have found that the measurement of pH and certain
      markers of oxidative stress, cytokines and prostanoids in exhaled breath
      condensate (EBC) may also be useful as well as the measurement of the temperature
      of exhaled breath and the analysis of volatile organic compounds (VOCs). In
      conclusion, since asthma is an inflammatory disease, it seems appropriate to try
      to control it through the study of airway inflammation using noninvasive methods.
      In this regard, the analysis of induced sputum cells has proved very useful,
      although the clinical implementation of this technique seems difficult. Other
      techniques such as temperature measurement, the analysis of FeNO, the analysis of
      the VOCs in exhaled breath, or the study of certain biomarkers in EBC require
      further study in order to determine their clinical applicability.

PMID- 25765084
TI  - Electronic effects in high-energy radiation damage in tungsten.
AB  - Although the effects of the electronic excitations during high-energy radiation
      damage processes are not currently understood, it is shown that their role in the
      interaction of radiation with matter is important. We perform molecular dynamics
      simulations of high-energy collision cascades in bcc-tungsten using the coupled
      two-temperature molecular dynamics (2T-MD) model that incorporates both the
      effects of electronic stopping and electron-phonon interaction. We compare the
      combination of these effects on the induced damage with only the effect of
      electronic stopping, and conclude in several novel insights. In the 2T-MD model,
      the electron-phonon coupling results in less damage production in the molten
      region and in faster relaxation of the damage at short times. These two effects
      lead to a significantly smaller amount of the final damage at longer times. 

PMID- 25765085
TI  - The complete mitochondrial genome of Allocricetulus eversmanni (Rodentia:
      Cricetidae).
AB  - Allocricetulus eversmanni is a unique species in the Allocricetulus, belonging to
      the Cricetinae group. Its complete mitochondrial genome was first obtained and
      the total length was 16,282 bp. Protein-coding genes approximately accounted for
      69.6% of the complete genome. The heavy strand contained 30% A, 14.4% G, 27.9% C,
      27.7% T. Compared with most other mammals, it had the same arrangement and
      similar length of vary genes or regions. The complete mitochondrial genome of A.
      eversmanni was conducive to more accurately locate its taxonomic status in
      Cricetinae and its evolutionary history. At the same time, it provided
      significant information about consummation of A. eversmanni gene pool.

PMID- 25765086
TI  - Complete mitochondrial genome of striped gourami, Trichogaster fasciata
      (Perciformes: Osphronemidae).
AB  - The complete mitochondrial genome of Trichogaster fasciata is determined in this
      study. It is 16,635 bp in size and consists of 2 rRNA genes, 13 protein-coding
      genes, 22 tRNA genes and 1 non-coding control region (D-loop). The overall base
      composition of the heavy strand of the T. fasciata mitochondrial genome is A:
      29.18%, T: 30.22%, C: 25.14%, and G: 15.46%. A 78 bp AT tandem repeats was
      identified in the control region. This present study will be helpful to bring out
      the fact of genetic divergence among the genus Trichogaster.

PMID- 25765087
TI  - Complete mitochondrial genome of yellow-browed tit (Sylviparus modestus).
AB  - The complete mitochondrial genome of yellow-browed tit was 17,086 bp in length,
      and consisted of 13 protein-coding genes, 22 tRNA genes, 2 rRNA genes and a
      control region. In control region, a 117 bp long tandem repeat was identified,
      which was the first reported tandem repeats in tits.

PMID- 25765088
TI  - Laser Therapy for Bladder Outlet Obstruction: A Prospective Analysis of All
      Patients Receiving Treatment with the GreenLight XPS 180-Watt Laser System after
      Introduction at a Single Center.
AB  - OBJECTIVE: The objective was to assess and publish our first experiences with the
      GreenLight XPSTM 180-watt laser in men suffering from bladder outlet obstruction.
      PATIENTS AND METHODS: From January 2013 to February 2014, the results of 142
      patients were analyzed prospectively at a single center. Indications for
      disobstruction were in line with current EAU guidelines, but independent of the
      underlying causes of obstruction. Assessments were made of the prostate size,
      International Prostate Symptom Score (IPSS), postvoid residual (PVR) and maximum
      urinary flow (Qmax). Intraoperative data such as lasing time, surgery time,
      applied energy and blood transfusions were recorded. Reinterventions and
      complications were evaluated. RESULTS: The average prostate volume was 29.6 ml (2
      82). The average surgery time was 50 min (13-157). Qmax increased by an average
      of 20.2 ml/s (p < 0.05). On average, PVR was reduced by 162 ml (p < 0.05).
      CONCLUSION: The GreenLight XPSTM 180-watt laser is an effective treatment option
      for bladder outlet obstruction with a low perioperative complications rate, and
      it shows results comparable with transurethral resection of the prostate. Even
      multimorbid patients and patients with long-term catheter requirements may be
      treated due to its high safety profile and reliable results.

PMID- 25765089
TI  - Chondroprotective effects of taurine in primary cultures of human articular
      chondrocytes.
AB  - Articular cartilage is characterized by the lack of blood vessels and has a poor
      self-healing potential. Limited cell numbers and dedifferentiation of
      chondrocytes when expanded in vitro are the major obstacles of autologous
      chondrocyte implantation. Autologous chondrocyte implantation is a cell-based
      treatment that can be used as a second-line measure to regenerate chondral or
      osteochondral defects in younger, active patients. There is an urgent need to
      find an effective chondrogenic protection agent alleviating or inhibiting
      chondrocyte dedifferentiation. In this study, we explored the effect of taurine
      (2-aminoethane sulfonic acid) on proliferation and phenotype maintenance of human
      articular chondrocytes by analyzing the cell proliferation, morphology,
      viability, and expression of cartilage specific mRNAs and proteins. Primary
      chondrocytes were isolated from human articular cartilage tissues. Results showed
      that taurine effectively promoted chondrocyte growth and enhanced accumulation of
      glycosaminoglycans and collagens in the conditioned media of chondrocytes.
      Moreover, taurine exposure caused significant increases in the relative
      expression levels of mRNAs for cartilage specific markers, including aggrecan,
      collagen type II and SOX9. Aggrecan is a cartilage-specific proteoglycan, and
      SOX9 is a chondrogenic transcription factor. In contrast, the mRNA expression of
      collagen type I, a marker for chondrocyte dedifferentiation, was significantly
      decreased in cells treated with taurine, indicating that taurine inhibits the
      chondrocyte dedifferentiation. This study reveals that taurine is effective in
      proliferation promotion and phenotype maintenance of chondrocytes. Thus, taurine
      may be a useful pro-chondrogenic agent for autologous chondrocyte implantation in
      the treatment of cartilage repair. 

PMID- 25765090
TI  - Ghrelin and obestatin in thyroid gland - immunohistochemical expression in
      nodular goiter, papillary and medullary cancer.
AB  - INTRODUCTION: Previous studies analyzing ghrelin and obestatin expression in
      thyroid gland tissue are not unanimous and are mostly related to ghrelin. The
      role of ghrelin and obestatin in the thyroid gland appears very interesting due
      to their probable involvement in cell proliferation. Furthermore, since the
      thyroid gland is associated with the maintenance of energy balance, the
      relationship between ghrelin, obestatin and thyroid function is worthy of
      consideration. The aim of the study was to assess ghrelin and obestatin
      immunocytochemical expression in nodular goiter (NG), papillary cancer (PTC) and
      medullary cancer (MTC). MATERIAL AND METHODS: Analyzed samples included 9 cases
      of NG, 8 cases of PTC and 11 cases of MTC. The analysis of ghrelin and obestatin
      expression was performed by use of the immunohistochemical (IHC) EnVision system
      and evaluated with filter HSV software (quantitative morphometric analysis).
      RESULTS: Quantitative ghrelin expression in MTC cells was higher than in NG (p =
      0.013) and correlated negatively with the size of the tumor (r= -0.829, p <
      0.05). We did not observe any differences in ghrelin expression neither between
      MTC and PTC nor between NG and PTC. Obestatin immunoexpression pattern in all
      analyzed specimens was irregular and poorly accented. The strongest
      immunoreactivity for obestatin was demonstrated in NG. In MTC obestatin
      expression was significantly weaker than in NG and PTC (p < 0.05 in both cases).
      In NG the intensity of obestatin immunostaining was significantly higher than
      that of ghrelin (p = 0.03). Conversely, ghrelin expression in MTC was definitely
      more evident than obestatin immunoreactivity (p < 0.01). There was no
      statistically significant difference between ghrelin and obestatin expression in
      PTC. No correlations were detected between reciprocal tissue expressions of
      ghrelin and obestatin in the analyzed specimens of NG, PTC or MTC. CONCLUSIONS:
      The differences between ghrelin expression in NG and MTC suggest that ghrelin may
      be involved in thyroid cell proliferation. The differences between ghrelin and
      obestatin immunoreactivity in benign and malignant thyroid tumors could support
      the theory of alternative transcription of the preproghrelin gene and independent
      production of ghrelin and obestatin.

PMID- 25765091
TI  - Impaired expression of sex hormone receptors in male reproductive organs of
      diabetic rat in response to oral antidiabetic drugs.
AB  - INTRODUCTION: Few oral antidiabetic drugs have been evaluated for their
      reproductive complication. This study aimed to evaluate the effect of metformin,
      pioglitazone and sitagliptin on the structure of male reproductive system through
      an immunohistopathological study. MATERIAL AND METHODS: Sprague-Dawley male rats
      were injected with streptozotocin. The diabetic rats were divided into four
      groups (n = 8/each group); diabetic control, metformin-, pioglitazone- and
      sitagliptin-treated groups in addition to a normal control group (n = 8). At the
      end of the experiment, blood samples were collected for biochemical assessment.
      Testis, epididymis and seminal vesicle were dissected and processed for
      histopathological examination using routine and immune-staining. RESULTS: All
      drugs significantly (p < 0.05) decreased fasting blood glucose, glycated
      hemoglobin, total cholesterol, triglycerides and malondialdehyde compared to the
      diabetic control group. Metformin has induced the least pathologic changes on the
      structure of the testis, epididymis and seminal vesicle among the studied drugs.
      Metformin succeeded to restore weights of testis, epididymis and seminal vesicle
      as well as testosterone hormone level back to values of the NC group while the
      pioglitazone and sitagliptin failed to do that. A significant reduction (p <
      0.05) in testicular ERa and ERb immunoexpression of pioglitazone-treated group as
      well as suppression of ERb and AR immunoreactivity in in epididymus and seminal
      vesicles of pioglitazone- and sitagliptin-treated rats were observed compared to
      the control animals. CONCLUSIONS: Histological structure as well ER and AR
      expression in the system organs were negatively and significantly affected with
      all studied drugs. Metformin has the least effect on the structure of the studied
      male reproductive organs. Thus, pioglitazone and sitagliptin treatment should be
      avoided in young male diabetic patients.

PMID- 25765092
TI  - The effects of streptozotocin-induced diabetes on ghrelin expression in rat
      testis: biochemical and immunohistochemical study.
AB  - INTRODUCTION: Ghrelin is a hormone which has effects on the secretion of growth
      hormone, gastrointestinal system, cardiovascular system, cell proliferation and
      reproductive system. The present study we focused on the relation between ghrelin
      and GHS-R1a gene expression and the regulation of their expression in the testes
      of diabetic rats. MATERIAL AND METHODS: 40 male Wistar albino rats were divided
      into four groups: control, and sampled 4, 8 and 12 weeks after induction of
      diabetes by streptozotocin (STZ) intraperitoneal injection (40 mg/kg). The rats
      were decapitated under ketamine anesthesia and their testes were removed. Blood
      was obtained from heart and serum follicle stimulating hormone (FSH), luteinizing
      hormone (LH), and testosterone levels were measured by ELISA. Tissue ghrelin and
      GHS-R mRNA levels were determined by qRT-PCR, while ghrelin protein expression
      was studied by immunohistochemistry. Histopathological damage scores were also
      assessed. RESULTS: Eight weeks after diabetes induction serum FSH level was
      increased, whereas LH and testosterone concentrations decreased. The ghrelin and
      GHS-R1a gene expression and ghrelin immunohistochemistry score first tended to
      increase after first four weeks of diabetes, and then tended to decrease. Ghrelin
      immunopositive cells were detected in Leydig cells in all groups of rats,
      however, not in the germinal epithelium. Congestion of vessels and hemorrhage,
      formation of the vacuoles in spermatogonia and spermatocytes, desquamation of
      spermatids in the lumen and disorganization of seminiferous tubule germinal
      epithelium were observed in testis of all the diabetic rats. In addition, mean
      testicular biopsy score and mean seminiferous tubule diameter were getting lower
      in diabetic animals. CONCLUSION: Our results suggest that diabetes affects
      ghrelin expression in rat testis.

PMID- 25765093
TI  - Hepatoprotective benzofurans and furanolignans from Gymnema tingens.
AB  - Two new benzofurans, gymnefuranols A (1) and B (2), together with six known
      furanolignans (3-8), were isolated from Gymnema tingens. The structures of the
      new compounds were elucidated by comprehensive analysis of the NMR and HR-MS
      data. Compounds 1, 2, 6, and 7 showed hepatoprotective activities against D
      galactosamine-induced HL-7702 cell damage. 

PMID- 25765094
TI  - Organization and behavior of the synaptonemal complex during achiasmatic meiosis
      of four buthid scorpions.
AB  - Testicular cells of 4 buthid scorpions, Rhopalurus agamemnon (2n = 28), R. rochai
      (2n = 28), Tityus bahiensis (2n = 6), and T. fasciolatus (2n = 14), which show
      different types of chromosomal configurations in meiosis I, were subjected to
      cellular microspreading in order to (1) obtain knowledge about the organization
      and behavior of the synaptonemal complex (SC), and (2) acquire data about the
      mechanisms responsible for inter- and intraindividual chromosomal variation
      within Buthidae. Ultrastructural analysis of microspread nuclei revealed SCs with
      a well-preserved structure until late substages of prophase I, but did not detect
      kinetochore plates and recombination nodules. Pachytene cells of R. agamemnon, R.
      rochai and T. bahiensis exhibited single and unsynapsed axes continuous with
      totally synapsed SCs, indicating the occurrence of heterozygous chromosomal
      rearrangements. Although chromosome chains were not observed in T. fasciolatus,
      the presence of gaps and interlocks points out that this species also carries
      heterozygous rearrangements, involving a small chromosome segment. Especially in
      R. rochai, the cellular microspreading analysis was useful to clarify the origin
      of inter- and intraindividual variation in the number of bivalent-like elements
      and in the number of chromosomes involved in multivalent associations. It was
      found that more chromosomes were involved in rearrangements than previously
      established through investigations using light microscopy alone.

PMID- 25765095
TI  - Plasticity and epistasis strongly affect bacterial fitness after losing multiple
      metabolic genes.
AB  - Many bacterial lineages lack seemingly essential metabolic genes. Previous work
      suggested selective benefits could drive the loss of biosynthetic functions from
      bacterial genomes when the corresponding metabolites are sufficiently available
      in the environment. However, the factors that govern this "genome streamlining"
      remain poorly understood. Here we determine the effect of plasticity and
      epistasis on the fitness of Escherichia coli genotypes from whose genome
      biosynthetic genes for one, two, or three different amino acids have been
      deleted. Competitive fitness experiments between auxotrophic mutants and
      prototrophic wild-type cells in one of two carbon environments revealed that
      plasticity and epistasis strongly affected the mutants' fitness individually and
      interactively. Positive and negative epistatic interactions were prevalent, yet
      on average cancelled each other out. Moreover, epistasis correlated negatively
      with the expected effects of combined auxotrophy-causing mutations, thus
      producing a pattern of diminishing returns. Moreover, computationally analyzing
      1,432 eubacterial metabolic networks revealed that most pairs of auxotrophies co
      occurred significantly more often than expected by chance, suggesting epistatic
      interactions and/or environmental factors favored these combinations. Our results
      demonstrate that both the genetic background and environmental conditions
      determine the adaptive value of a loss-of-biochemical-function mutation and that
      fitness gains decelerate, as more biochemical functions are lost.

PMID- 25765096
TI  - Stigma and GPs' perceptions of dementia.
AB  - OBJECTIVES: General practitioners (GPs) are crucial to improving timely
      diagnosis, but little is reported about how they perceive dementia, and whether
      their perceptions display any elements of stigma. The aim of this study was to
      explore how GPs' perceptions of dementia map onto current conceptualizations of
      stigma and whether GPs feel that stigma affects timely diagnosis. METHODS: Twenty
      three GPs from England were interviewed by telephone. Data were analyzed by means
      of content analysis. This involved open coding followed by the application of a
      coding framework derived from the literature to explore how and to what extent
      their perceptions relate to stigma as well as the unique nature of their
      perceptions. RESULTS: Three themes emerged from the analysis: (1) 'making sense
      of dementia', (2) 'relating perceptions of dementia to oneself' and (3)
      'considering the consequences of dementia'. GPs' perceptions of dementia mapped
      onto current conceptualizations of stigma. Perceptions about dementia that were
      linked to their own existential anxiety and to a perceived similarity between
      people with dementia and themselves were particularly salient. GPs perceived
      dementia as a stigma which was gradually being overcome but that stigma still
      hindered timely diagnosis. They provided examples of structural discrimination
      within the health service, including lack of time for patients and shortcomings
      in training that were to the detriment of people with dementia. CONCLUSION:
      Measures to involve GPs in tackling stigma should include training and
      opportunities to explore how they perceive dementia, as well as support to
      address structural discrimination.

PMID- 25765097
TI  - Neurotological parameters and prognosis of Bell's palsy patients.
AB  - BACKGROUND: To investigate the relationship with prognosis, various
      neurotological examinations evaluating all four nerves within the internal
      auditory canal were performed in patients with Bell's palsy. METHODS: A total of
      69 consecutive patients with Bell's palsy were included. They were treated
      uniformly with steroid and an antiviral agent and underwent neurotological
      examinations consisting of electronystagmography, pure-tone audiometry (PTA),
      electroneurography (ENoG), caloric test, rotatory chair test and cervical
      vestibular evoked myogenic potentials (cVEMP). According to the final recovery
      state, patients were divided into two groups: a complete recovery group and an
      incomplete recovery group. The incidence of abnormal findings in each test was
      compared between the two groups. RESULTS: Fifty-six patients recovered completely
      and 13 patients recovered incompletely. No association was observed between the
      rate of ipsilesional PTA threshold and the rate of abnormal caloric test,
      function tests and recovery state. However, the initial state of facial palsy,
      ENoG and the rate of abnormal cVEMP were significantly correlated with the rate
      of recovery. CONCLUSION: The results indicate that Bell's palsy may be more
      comparable to mononeuritis multiplex and that cVEMP could be a useful tool for
      predicting the prognosis of Bell's palsy.

PMID- 25765098
TI  - Geographic distribution of regional metastatic nodes affects the outcome of
      trimodality-eligible patients with esophageal adenocarcinoma.
AB  - BACKGROUND/AIM: Malignant nodes in patients with localized esophageal
      adenocarcinoma (L-EAC) portend a poor prognosis. We assessed the correlation of
      the distribution of nodes with the outcome of patients undergoing
      chemoradiation/surgery (trimodality therapy). METHODS: We studied 209 L-EAC
      patients who had confirmed or suspicious nodes at baseline staging. All patients
      received trimodality therapy and were grouped according to the nodal geography:
      above the diaphragm (AD), below the diaphragm (BD), or above and below the
      diaphragm (ABD). Survival estimates were calculated using the Kaplan-Meier
      method, and the outcomes of the groups were assessed by the log-rank test.
      RESULTS: Patients were primarily Caucasian (91%) and male (93%), with a baseline
      stage III L-EAC (89%). The median follow-up was 2.8 years (range, 0.4-11.7). Of
      the 209 patients, 35% (n = 73) had AD nodes, 20% (n = 41) had BD nodes, and 45%
      (n = 95) had ABD nodes. ABD patients had a 5-year overall survival rate of 33%,
      whereas this rate was 55% in AD patients and 60% in BD patients (p = 0.02).
      Patients with a higher histology grade were also at a higher risk of relapse and
      had a poor survival (p < 0.01 for both). CONCLUSIONS: L-EAC patients in the ABD
      group had the worst outcome after trimodality treatment compared to those in the
      AD or BD group. Novel strategies are needed for ABD patients.

PMID- 25765099
TI  - Recombinant human growth hormone plus recombinant human insulin-like growth
      factor-1 coadministration therapy in short children with low insulin-like growth
      factor-1 and growth hormone sufficiency: results from a randomized, multicenter,
      open-label, parallel-group, active treatment-controlled trial.
AB  - BACKGROUND/AIMS: Growth hormone (GH) and insulin-like growth factor-1 (IGF-1)
      both contribute to growth. To determine if recombinant human (rh)GH + rhIGF-1
      therapy is more effective than rhGH alone to treat short stature, we assessed the
      efficacy and safety of coadministered rhGH + rhIGF-1 in short children with GH
      sufficiency and low IGF-1. METHODS: In a 3-year, randomized, multicenter, open
      label trial, patients with height SD score <=-2.0 and IGF-1 SD score <=-1.0 for
      age and sex, and with stimulated GH >=10 ng/ml for age and sex, were randomized
      to receive (all doses in ug/kg/day): 45 rhGH alone (group A), 45 rhGH + 50 rhIGF
      1 (group B), 45 rhGH + 100 rhIGF-1 (group C) or 45 rhGH + 150 rhIGF-1 (group D).
      Height velocity (HV) and Delta height SD score were measured. RESULTS: The first
      year HV (modified intention-to-treat population) was 9.3 +/- 1.7 cm/year (group
      A), 10.1 +/- 1.3 cm/year (group B), 9.7 +/- 2.5 cm/year (group C) and 11.2 +/-
      2.1 cm/year (group D) (p = 0.001 for groups A vs. D). This effect was sustained,
      resulting in a height SD score improvement during the second and third years.
      Most treatment-emergent adverse events were mild and transient. CONCLUSION: In
      children with short stature, GH sufficiency and low IGF-1, coadministration of
      rhGH/rhIGF-1 (45/150 ug/kg) significantly accelerated linear growth compared with
      rhGH alone, with a safety profile similar to the individual monotherapies.

PMID- 25765100
TI  - Expression of Somatostatin Receptors 1-5 and Dopamine Receptor 2 in Lung
      Carcinoids: Implications for a Therapeutic Role.
AB  - OBJECTIVE: The expression of somatostatin receptors (SSTRs) and dopamine receptor
      2 (DR2) in neuroendocrine tumors is of clinical importance as somatostatin
      analogues and dopamine agonists can be used for their localization and/or
      treatment. The objective of this study is to examine the expression of the five
      SSTR subtypes and DR2 in lung carcinoids (LCs). METHODS: We conducted a
      retrospective study of 119 LCs from 106 patients [typical carcinoids (TCs): n =
      100, and atypical carcinoids (ACs): n = 19]. The expression of all five SSTR
      subtypes and DR2 was evaluated immunohistochemically and correlated to
      clinicopathological data. In a subgroup of cases, receptor expression was further
      analyzed using semiquantitative RT-PCR. RESULTS: SSTR2A was the SSTR subtype most
      frequently expressed immunohistochemically (72%), followed by SSTR1 (63%), SSTR5
      (40%), and SSTR3 (20%), whereas SSTR4 was negative. DR2 was expressed in 74% and
      co-expressed with SSTR1 in 56%, with SSTR2A in 59%, with SSTR3 in 19%, and with
      SSTR5 in 37% of the tumors. Receptor expression was not related to the
      histological subtype, tumor aggressiveness (disease extent/grading) or
      functionality; however, DR2 was expressed more frequently in ACs than TCs (95 vs.
      70%, p = 0.017). In a subset of patients, RT-PCR findings highly suggested that
      the expression of SSTR2A, SSTR3, DR2, and to a lesser extent that of SSTR1 and
      SSTR5 is the outcome of increased gene transcription. CONCLUSIONS: The high and
      variable immunohistochemical expression of the majority of SSTRs along with their
      co-expression with DR2 in LCs provides a rationale for their possible treatment
      with agents that target these receptors.

PMID- 25765101
TI  - Topographic Analysis of Electroencephalographic Changes during Photic Driving
      Responses in Patients with Migraine.
AB  - OBJECTIVE: Migraineurs demonstrate abnormal information processing such as photic
      hypersensitivity. The photic driving response to photic stimulation (PS) is a
      reaction to the visual stimulation of electroencephalography (EEG). Both the
      photic driving response and photic hypersensitivity appear during light
      stimulation. We considered that evaluation of a migraineur's photic driving
      response may help to elucidate the mechanism of the migraineur's sensitive
      condition. Our study aimed to investigate EEG photic driving responses with a
      source-localizing method. METHODS: We recorded spontaneous resting EEG with eyes
      closed from 20 electrodes on the scalp during the interictal phase. After
      recording, each PS was separately selected. We also analyzed EEG by fast Fourier
      transform and observed the spectrum frequency peaks and topographies in response
      to PS. RESULTS: The photic driving response could be observed at a flashing rate
      of >15 Hz. Patients with photic hypersensitivity tended to show more photic
      driving regardless of the migraine subtype. Moreover, in topographies, their
      activated areas were shifted anteriorly from fundamental driving to harmonic
      driving for each photic frequency. This anterior shift was more evident with a
      longer duration of illness, although no significant differences were seen between
      migraine subtypes. The global field power value had a positive correlation with
      the duration of illness. CONCLUSION: Photic hypersensitivity and photic driving
      responses were increased in migraineurs. Photic hypersensitivity might result in
      sensitization of the limbic system. (c) 2015 S. Karger AG, Basel.

PMID- 25765102
TI  - Culture, types of social withdrawal, and children's beliefs: An integrative
      perspective.
AB  - Cultural norms and values provide guidance for children to judge and evaluate
      specific behavioural characteristics including shyness, unsociability, and social
      avoidance. The perceptions and attitudes of children, in turn, determine how they
      exhibit and regulate their behaviours and how they respond to peers' behaviours
      in social interactions. Investigation of children's beliefs across societies may
      shed some light on the processes in which culture is involved in shaping the
      display and developmental significance of different types of social withdrawal.
      To achieve a better understanding of the role of children's beliefs in mediating
      cultural influence on development, it will be important to examine how children's
      beliefs about withdrawn behaviours are associated with patterns of social
      interactions and relationships in various circumstances. 

PMID- 25765103
TI  - Tuberculosis diagnostics in 2015: landscape, priorities, needs, and prospects.
AB  - In 2015, tuberculosis remains a major global health problem, and drug-resistant
      tuberculosis is a growing threat. Although tuberculosis diagnosis in many
      countries is still reliant on older tools, new diagnostics are changing the
      landscape. Stimulated, in part, by the success and roll out of Xpert MTB/RIF,
      there is now considerable interest in new technologies. The landscape looks
      promising, with a robust pipeline of new tools, particularly molecular
      diagnostics, and well over 50 companies actively engaged in product development.
      However, new diagnostics are yet to reach scale, and there needs to be greater
      convergence between diagnostics development and development of shorter-duration
      tuberculosis drug regimens. Another concern is the relative absence of non-sputum
      based diagnostics in the pipeline for children and of biomarker tests for triage,
      cure, and progression of latent Mycobacterium tuberculosis infection. Several
      initiatives, described in this supplement, have been launched to further
      stimulate product development and policy, including assessment of needs and
      priorities, development of target product profiles, compilation of data on
      resistance-associated mutations, and assessment of market size and potential for
      new diagnostics. Advocacy is needed to increase funding for tuberculosis research
      and development, and governments in high-burden countries must invest more in
      tuberculosis control to meet post-2015 targets for care, control, and prevention.

PMID- 25765104
TI  - Defining the needs for next generation assays for tuberculosis.
AB  - To accelerate the fight against tuberculosis, major diagnostic challenges need to
      be addressed urgently. Post-2015 targets are unlikely to be met without the use
      of novel diagnostics that are more accurate and can be used closer to where
      patients first seek care in affordable diagnostic algorithms. This article
      describes the efforts by the stakeholder community that led to the identification
      of the high-priority diagnostic needs in tuberculosis. Subsequently target
      product profiles for the high-priority diagnostic needs were developed and
      reviewed in a World Health Organization (WHO)-led consensus meeting. The high
      priority diagnostic needs included (1) a sputum-based replacement test for smear
      microscopy; (2) a non-sputum-based biomarker test for all forms of tuberculosis,
      ideally suitable for use at levels below microscopy centers; (3) a simple, low
      cost triage test for use by first-contact care providers as a rule-out test,
      ideally suitable for use by community health workers; and (4) a rapid drug
      susceptibility test for use at the microscopy center level. The developed target
      product profiles, along with complimentary work presented in this supplement,
      will help to facilitate the interaction between the tuberculosis community and
      the diagnostics industry with the goal to lead the way toward the post-2015
      global tuberculosis targets. 

PMID- 25765106
TI  - Integration of published information into a resistance-associated mutation
      database for Mycobacterium tuberculosis.
AB  - Tuberculosis remains a major global public health challenge. Although incidence
      is decreasing, the proportion of drug-resistant cases is increasing. Technical
      and operational complexities prevent Mycobacterium tuberculosis drug
      susceptibility phenotyping in the vast majority of new and retreatment cases. The
      advent of molecular technologies provides an opportunity to obtain results
      rapidly as compared to phenotypic culture. However, correlations between genetic
      mutations and resistance to multiple drugs have not been systematically
      evaluated. Molecular testing of M. tuberculosis sampled from a typical patient
      continues to provide a partial picture of drug resistance. A database of
      phenotypic and genotypic testing results, especially where prospectively
      collected, could document statistically significant associations and may reveal
      new, predictive molecular patterns. We examine the feasibility of integrating
      existing molecular and phenotypic drug susceptibility data to identify
      associations observed across multiple studies and demonstrate potential for well
      integrated M. tuberculosis mutation data to reveal actionable findings. 

PMID- 25765107
TI  - Potential market for novel tuberculosis diagnostics: worth the investment?
AB  - BACKGROUND: The potential available market (PAM) for new diagnostics for
      tuberculosis that meet the specifications of the high-priority target product
      profiles (TPPs) is currently unknown. METHODS: We estimated the PAM in 2020 in 4
      high-burden countries (South Africa, Brazil, China, and India) for tests that
      meet the specifications outlined in the TPPs. The yearly PAM was estimated for
      the most likely application of each TPP. RESULTS: In 2020 the PAM for all 4
      countries together was estimated to be (1) 12M tests/year with a value of 48M-71M
      USD for a sputum smear-replacement test; (2) 16M tests/year with a value of 65M
      97M USD for a biomarker test; (3) 18M tests/year with a value of 18M-35M USD for
      a triage test; (4) 12M tests/year with a value of 59M-2238M USD for a
      tuberculosis detection plus drug susceptibility test (DST) all-in-one or 1.5M
      tests/year for a DST that follows a positive tuberculosis detection test with a
      corresponding value of 75M-121M for both tuberculosis detection and DST.
      CONCLUSIONS: Although there is a considerable potential market for novel
      tuberculosis diagnostics that fit the specification of the TPPs in the 4 high
      burden countries, the actual market for an individual product remains uncertain.

PMID- 25765105
TI  - Target product profile of a molecular drug-susceptibility test for use in
      microscopy centers.
AB  - BACKGROUND: Current phenotypic testing for drug resistance in patients with
      tuberculosis is inadequate primarily with respect to turnaround time. Molecular
      tests hold the promise of an improved time to diagnosis. METHODS: A target
      product profile for a molecular drug-susceptibility test (DST) was developed on
      the basis of a collaborative effort that included opinions gathered from
      researchers, clinicians, policy makers, and test developers on optimal clinical
      and operational characteristics in settings of intended use. In addition, the
      current diagnostic ecosystem and the diagnostic development landscape were
      mapped. RESULTS: Molecular DSTs for detecting tuberculosis in microscopy centers
      should ideally evaluate for resistance to rifampin, fluoroquinolones, isoniazid,
      and pyrazinamide and enable the selection of the most appropriate treatment
      regimen. Performance characteristics of DSTs need to be optimized, but
      compromises can be made that depend on the trade-off between a false-positive
      result and a false-negative result. The operational requirements of a test will
      vary depending on the site of implementation. However, the most-important
      considerations pertain to quality control, maintenance and calibration, and the
      ability to export data. CONCLUSION: This target product profile defines the needs
      as perceived by the tuberculosis stakeholder community and attempts to provide a
      means of communication with test developers to ensure that fit-for-purpose DSTs
      are being developed.

PMID- 25765108
TI  - Costs of novel tuberculosis diagnostics--will countries be able to afford it?
AB  - BACKGROUND: Four priority target product profiles for the development of
      diagnostic tests for tuberculosis were identified: 1) Rapid sputum-based (RSP),
      2) non-sputum Biomarker-based (BMT), 3) triage test followed by confirmatory test
      (TT), and 4) drug-susceptibility testing (DST). METHODS: We assessed the cost of
      the new tests in suitable strategies and of the conventional diagnosis of
      tuberculosis as per World Health Organization guidelines, in 36 high tuberculosis
      and MDR burden countries. Costs were then compared to the available funding for
      tuberculosis at country level. RESULTS: Costs of diagnosing tuberculosis using
      RSP ranged US$93-187 million/year; if RSP unit cost is of US$2-4 it would be
      lower/similar cost than conventional strategy with sputum smear microscopy (US$
      119 million/year). Using BMT (with unit cost of US$2-4) would cost US$70-121
      million/year and be lower/comparable cost than conventional diagnostics. Using TT
      with TPP characteristics (unit cost of US$1-2) followed by Xpert would reduce
      diagnostic costs up to US$36 million/year. Costs of using different novel DST
      strategies for the diagnosis of drug resistance would be higher compared with
      conventional diagnosis. CONCLUSIONS: Introducing a TT or a biomarker test with
      optimal characteristics would be affordable from a cost and affordability
      perspective at the current available funding for tuberculosis. Additional
      domestic or donor funding would be needed in most countries to achieve
      affordability for other new diagnostic tests.

PMID- 25765109
TI  - Discovery, innovation, and new frontiers in tuberculosis diagnostics: reflections
      and expectations.

PMID- 25765110
TI  - Suppressive Effects of Chronic Stress on Influenza Virus Protection after
      Vaccination with Plasmid DNA-Encoded Nucleoprotein.
AB  - BACKGROUND: Influenza is a highly infectious and acute respiratory disease caused
      by an infection of the host respiratory tract mucosa by the influenza virus. The
      use of DNA vaccines that express conserved genes such as nucleoprotein (NP)
      represents a new method of vaccination against influenza. In this study, the
      effect of chronic stress on the efficiency of this type of vaccine has been
      evaluated in a mouse model. METHODS: The NP DNA vaccine was administered
      intradermally 3 times on days 0, 3 and 6 to stressed and nonstressed male BALB/c
      mice. Two weeks after the last immunization, half of these mice were challenged
      with A/Puerto Rico/8/34 (PR8) influenza virus and were weighed for 12 days, and
      their mortality rate was assessed during this period. The cellular immune
      response of the other half of the mice was evaluated by cytotoxicity assay.
      RESULTS: The results indicate a significant reduction in the cytotoxic T
      lymphocyte response of stressed mice in comparison with unstressed mice. Also,
      the percentage of weight loss and mortality after the challenge in stressed mice
      was significantly increased compared to the other group. CONCLUSION: These
      results indicate that the NP DNA vaccine is not able to induce any effective
      cytotoxic T-lymphocyte response against influenza virus in stressed mice and
      cannot induce protective immunity against influenza infection in this group of
      mice.

PMID- 25765111
TI  - Cyclin D1 is a useful marker for soft tissue Ewing's sarcoma/peripheral Primitive
      Neuroectodermal Tumor in children and adolescents: A comparative
      immunohistochemical study with rhabdomyosarcoma.
AB  - Cyclin D1 amplification and/or overexpression contribute to the loss of the
      regulatory circuits that govern G1-S transition phase of the cell cycle, playing
      pivotal roles in different human malignant tumors, including breast, colon,
      prostate cancer, lymphoma, melanoma and neuroblastoma. In vitro studies have
      shown that cyclin D1 is overexpressed in Ewing's sarcoma (EWS)/peripheral
      Primitive Neuroectodermal Tumor (pPNET), but not in rhabdomyosarcoma cell lines.
      Only a few immunohistochemical studies are available on cyclin D1 expression in
      EWS/pPNET, which confirmed its expression only in a limited number of cases. The
      aim of the present study was a comparative immunohistochemical analysis of the
      expression and distribution of cyclin D1 in a large series of
      pediatric/adolescent soft tissue EWS/pPNETs and rhabdomyosarcomas (both embryonal
      and alveolar subtypes) to assess its potential usefulness in their differential
      diagnosis. Notably cyclin D1 was strongly and diffusely expressed in all cases
      (20/20) of EWS/pPNET, while it was lacked in all cases (15/15) of
      rhabdomyosarcomas. Immunohistochemical overexpression of cyclin D1 in EWS/pPNET
      is a novel finding which could be exploitable as a diagnostic immunomarker for
      this tumor. Although highly sensitive, cyclin D1 is not specific for EWS/pPNET,
      and thus it should not be evaluated alone but in the context of a wide
      immunohistochemical panel. Accordingly, we first emphasize that when pathologists
      are dealing with a small round blue cell tumor of soft tissues in
      pediatric/adolescent patients, a strong and diffuse nuclear expression of cyclin
      D1 is of complementary diagnostic value to CD99 and FLI-1 in confirming diagnosis
      of EWS/pPNET and in ruling out rhabdomyosarcoma. 

PMID- 25765112
TI  - MicroRNA and pediatric tumors: Future perspectives.
AB  - A better understanding of pediatric tumor biology is needed to allow the
      development of less toxic and more efficient therapies, as well as to provide
      novel reliable biomarkers for diagnosis and risk stratification. The emerging
      role of microRNAs in controlling key pathways implicated in tumorigenesis makes
      their use in diagnostics a powerful novel tool for the early detection, risk
      assessment and prognosis, as well as for the development of innovative anticancer
      therapies. This perspective would be more urgent for the clinical management of
      pediatric cancer. In this review, we focus on the involvement of microRNAs in the
      biology of the main childhood tumors, describe their clinical significance and
      discuss their potential use as novel therapeutic tools and targets. 

PMID- 25765113
TI  - Cyclin D1 in human neuroblastic tumors recapitulates its developmental
      expression: An immunohistochemical study.
AB  - The protein cyclin D1 (CD1), which belongs to a family of proteins functioning as
      regulators of CDKs (cyclin-dependent kinases) throughout the cell cycle, has been
      immunohistochemically detected in a wide variety of human malignant tumors. The
      aim of the present study was to investigate immunohistochemically the expression
      and distribution of CD1 in the developing human peripheral sympathetic nervous
      system (PSNS) and in childhood peripheral neuroblastic tumors (neuroblastomas,
      ganglioneuroblastomas, and ganglioneuromas). The above mentioned fetal and
      neoplastic tissues represent an in vivo model in which undifferentiated
      neuroblastic cells undergo ganglion cell differentiation. During development, a
      strong nuclear expression of CD1 was restricted to neuroblasts, disappearing
      progressively from the maturing ganglion cells with increasing gestational age.
      In neoplastic tissues, CD1 immunoreactivity was restricted to neuroblastic cell
      component of all neuroblastomas and ganglioneuroblastomas, whereas it was absent
      or only focally detectable in maturing/mature ganglion cell component of
      differentiating neuroblastomas, ganglioneuroblastomas, and ganglioneuromas. We
      conclude that CD1 is a reliable marker, which can be used routinely to stain
      neuroblastic cells in both developing and neoplastic tissues. Furthermore, our
      results indicate that CD1 expression in childhood peripheral neuroblastic tumors
      recapitulates the changes during normal development of PSNS, as previously
      reported for Bcl-2 oncoprotein, c-ErbB2, insulin-like growth factor 2, beta-2
      microglobulin, and cathepsin D. This is consistent with the current view that
      childhood peripheral neuroblastic tumors exhibit gene expression profiles
      mirroring those occurring during PSNS development. 

PMID- 25765114
TI  - Identification of sex-linked SNP markers using RAD sequencing suggests ZW/ZZ sex
      determination in Pistacia vera L.
AB  - BACKGROUND: Pistachio (Pistacia vera L.) is a dioecious species that has a long
      juvenility period. Therefore, development of marker-assisted selection (MAS)
      techniques would greatly facilitate pistachio cultivar-breeding programs. The sex
      determination mechanism is presently unknown in pistachio. The generation of sex
      linked markers is likely to reduce time, labor, and costs associated with
      breeding programs, and will help to clarify the sex determination system in
      pistachio. RESULTS: Restriction site-associated DNA (RAD) markers were used to
      identify sex-linked markers and to elucidate the sex determination system in
      pistachio. Eight male and eight female F1 progenies from a Pistacia vera L. Siirt
      * Bagyolu cross, along with the parents, were subjected to RAD sequencing in two
      lanes of a Hi-Seq 2000 sequencing platform. This generated 449 million reads,
      comprising approximately 37.7 Gb of sequences. There were 33,757 polymorphic
      single nucleotide polymorphism (SNP) loci between the parents. Thirty-eight of
      these, from 28 RAD reads, were detected as putative sex-associated loci in
      pistachio. Validation was performed by SNaPshot analysis in 42 mature F1
      progenies and in 124 cultivars and genotypes in a germplasm collection. Eight
      loci could distinguish sex with 100% accuracy in pistachio. To ascertain cost
      effective application of markers in a breeding program, high-resolution melting
      (HRM) analysis was performed; four markers were found to perfectly separate sexes
      in pistachio. Because of the female heterogamety in all candidate SNP loci, we
      report for the first time that pistachio has a ZZ/ZW sex determination system. As
      the reported female-to-male segregation ratio is 1:1 in all known segregating
      populations and there is no previous report of super-female genotypes or female
      heteromorphic chromosomes in pistachio, it appears that the WW genotype is not
      viable. CONCLUSION: Sex-linked SNP markers were identified and validated in a
      large germplasm and proved their suitability for MAS in pistachio. HRM analysis
      successfully validated the sex-linked markers for MAS. For the first time in
      dioecious pistachio, a female heterogamety ZW/ZZ sex determination system is
      suggested.

PMID- 25765116
TI  - Locked posterior dislocation of the shoulder: A report of three cases.
AB  - Posterior shoulder dislocations account for 4% of all shoulder dislocations. In
      two-thirds of the cases, the diagnosis is made only once the shoulder is locked,
      which radically changes the treatment and prognosis. We report three clinical
      cases of locked posterior shoulder dislocation. Closed reduction was attempted in
      one case but failed. All patients underwent open reduction and subscapularis
      transfer according to either Neer's (2 cases) or McLaughlin's technique (1 case).
      The functional outcome was satisfactory in two cases despite recurrent
      dislocation on the third day after surgery. The third patient eventually
      developed post-traumatic shoulder osteoarthritis. The best treatment consists of
      detecting posterior dislocations immediately when they occur under suggestive
      circumstances (electrocution, epileptic seizure, severe trauma shoulder).

PMID- 25765115
TI  - Transcriptome analysis of hen preadipocytes treated with an adipogenic cocktail
      (DMIOA) with or without 20(S)-hydroxylcholesterol.
AB  - BACKGROUND: 20(S)-hydroxycholesterol (20(S)) potentially reduces adipogenesis in
      mammalian cells. The role of this oxysterol and molecular mechanisms underlying
      the adipogenesis of preadipocytes from laying hens have not been investigated.
      This study was conducted to 1. Analyze genes differentially expressed between
      preadipocytes treated with an adipogenic cocktail (DMIOA) containing 500 nM
      dexamethasone, 0.5 mM 3-isobutyl-1-methylxanthine, 20 MUg/mL insulin and 300 MUM
      oleic acid (OA) and control cells and 2. Analyze genes differentially expressed
      between preadipocytes treated with DMIOA and those treated with DMIOA + 20(S)
      using Affymetrix GeneChip(r) Chicken Genome Arrays. RESULTS: In experiment one,
      where we compared the gene expression profile of non-treated (control) cells with
      those treated with DMIOA, out of 1,221 differentially expressed genes, 755 were
      over-expressed in control cells, and 466 were over-expressed in cells treated
      with DMIOA. In experiment two, where we compared the gene expression profile of
      DMIOA treated cells with those treated with DMIOA+20(S), out of 212
      differentially expressed genes, 90 were over-expressed in cells treated with
      DMIOA, and 122 were over-expressed in those treated with DMIOA+20(S). Genes over
      expressed in control cells compared to those treated with DMIOA include those
      involved in cell-to-cell signaling and interaction (IL6, CNN2, ITGB3), cellular
      assembly and organization (BMP6, IGF1, ACTB), and cell cycle (CD4, 9, 38). Genes
      over-expressed in DMIOA compared to control cells include those involved in
      cellular development (ADAM22, ADAMTS9, FIGF), lipid metabolism (FABP3, 4 and 5),
      and molecular transport (MAP3K8, PDK4, AGTR1). Genes over-expressed in cells
      treated with DMIOA compared with those treated with DMIOA+20(S) include those
      involved in lipid metabolism (ENPP2, DHCR7, DHCR24), molecular transport (FADS2,
      SLC6A2, CD36), and vitamin and mineral metabolism (BCMO1, AACS, AR). Genes over
      expressed in cells treated with DMIOA+20(S) compared with those treated with
      DMIOA include those involved in cellular growth and proliferation (CD44, CDK6,
      IL1B), cellular development (ADORA2B, ATP6VOD2, TNFAIP3), and cell-to-cell
      signaling and interaction (VCAM1, SPON2, VLDLR). CONCLUSION: We identified
      important adipogenic regulators and key pathways that would help to understand
      the molecular mechanism of the in vitro adipogenesis in laying hens and
      demonstrated that 20(S) is capable of suppressing DMIOA-induced adipogenesis.

PMID- 25765117
TI  - Tendon palpation during agonist contraction and antagonist co-contraction to
      assess wrist flexor and extensor muscle function.
AB  - The aim of this study was to validate direct tendon palpation during agonist
      contraction and antagonist co-contraction as a method to assess wrist flexor and
      extensor muscle function in cases of upper limb paralysis. On one occasion, five
      doctors examined 17 patients with partial paralysis of the upper limb resulting
      from brachial plexus or cervical spinal cord injury. We asked examiners to
      determine if the extensor carpi radialis longus (ECRL), extensor carpi radialis
      brevis (ECRB), extensor carpi ulnaris (ECU), flexor carpi radialis (FCR), flexor
      carpi ulnaris (FCU) and palmaris longus (PL) were paralyzed, weak or strong in
      each patient. Examiners tested flexion - extension and radial - ulnar deviation
      against resistance and palpated wrist motor tendons. While palpating tendons, co
      contractions were encouraged by soliciting finger extension to evaluate the FCU,
      thumb extension to evaluate the ECU, and finger flexion to evaluate the ECRB.
      Kappa values were 0.8 for the ECRL, 0.7 for the ECRB, 0.5 for the ECU, 0.8 for
      the FCR, 0.6 for the PL, and 0.8 for the FCU, indicating moderate to almost
      perfect agreement between examiners. Tendon palpation during muscle examination
      was adequate to identify complete paralysis, as well as weak and strong muscle
      contractions. This assessment helps to identify muscles that could be used during
      nerve or tendon transfer for reconstruction of extensive upper limb paralysis.

PMID- 25765118
TI  - Contemporary trends in the epidemiology of traumatic spinal cord injury: changes
      in age and etiology.
AB  - BACKGROUND: Epidemiological features of spinal cord injury (SCI) have been
      changing over the last decades. We evaluated the contemporary trends in the
      epidemiology of traumatic SCI patients from a rehabilitation center. METHODS: In
      a cross-sectional study, a consecutive series of 348 patients with traumatic SCI
      were evaluated. Variables were collected through an epidemiological form, which
      included gender, age at injury, duration and cause of SCI. We investigated SCI
      epidemiological trends over time including the association between gender and age
      at injury with SCI features such as etiology, injury severity and level. RESULTS:
      The mean age at SCI has increased from 26.0 +/- 11.8 in patients with SCI before
      2003 to 37.9 +/- 15.7 in those with SCI after 2009 (p < 0.001). Gunshot wounds
      were the main cause of injury in patients with SCI before 2003, dropping from
      40.6 to 16.9% after 2009 and being surpassed by road traffic injuries (38.6%) and
      falls (31.4%) after 2009 (p < 0.001). Gender, SCI severity and level have not
      changed significantly over the time. CONCLUSIONS: There was a major increase in
      the average age of patients as well as changes in the etiology of SCI over the
      past fifteen years, including a significant decrease in gunshot wounds and an
      increase in the frequency of road traffic injuries and falls. These changes and
      accompanying risk factors must be taken into consideration when planning measures
      to prevent SCI.

PMID- 25765119
TI  - [Influence of tobacco smoking on the risk of developing asthma].
AB  - The aim of this general review is to investigate the influence of active and
      passive smoking on the development of asthma in children and adults. Passive
      smoking during and after pregnancy facilitates the onset of childhood asthma and
      wheezing. In particular, smoking during pregnancy is associated with the
      occurrence of wheezing prior to the age of 4 years. In contrast, the results of
      studies on the relationship between parental smoking in the post-natal period and
      the onset of asthma or wheezing are discordant. Exposure to passive smoking
      during childhood facilitates the occurrence of asthma in adulthood. In adults and
      adolescents, active smoking appears to be a factor favoring the development of
      asthma. On the other hand, non-smoking adult subjects without history of asthma
      exposed to passive smoking have a risk of asthma. The pathophysiological
      mechanisms by which tobacco smoke is the cause of asthma are still poorly known.
      Smoking cessation is an essential component in the management of asthmatic
      subjects who smoke, facilitating the control of the disease.

PMID- 25765120
TI  - [Health effects of diesel exhaust: a state of the art].
AB  - INTRODUCTION: This review presents the state of knowledge regarding the acute and
      chronic toxicity of diesel engine exhaust in humans. STATE OF ART: The health
      effects of diesel engine exhaust, which is a complex mixture of gas and
      particulate matter (ultrafine and fine particles), are mainly irritation of the
      respiratory tract and carcinogenicity. They may also facilitate the development
      of respiratory allergies. A recent reassessment by the International Agency for
      Research on Cancer concluded that there is sufficient evidence of a causal
      association between exposure to diesel engine exhaust and lung cancer.
      PERSPECTIVES: The epidemiologic data collected during the last two decades also
      show limited evidence of increased risks of bladder cancer, as well as of chronic
      obstructive pulmonary disease in diesel engine exhaust exposed workers. Both
      experimental and epidemiological studies have involved the effect of emissions
      from traditional diesel engine technology. Major developments in this technology
      have occurred recently and the toxicity of emissions from these new engines is
      still to be characterized. CONCLUSION: Further studies are needed to explore the
      link between diesel engine exhaust exposure and the risks of bladder cancer, as
      well as of chronic obstructive pulmonary disease and respiratory allergies.
      Research is also needed to get more information about the toxicity of the new
      diesel technology emissions.

PMID- 25765121
TI  - [Reflections on the limits of specific treatments in thoracic oncology].
AB  - The modest impact of specific treatments is a major problem in oncology and
      particularly for metastatic lung cancer patients. Therapeutic progress achieved
      by some targeted therapies is, in fact, only relevant for a small proportion of
      patients. The vast majority of people with this condition are rapidly confronted
      by the limits of specific therapies and management is or becomes entirely
      palliative. This article addresses therapeutic limitations in the management of
      metastatic lung cancer, as well as legislative aspects and guidelines for
      practitioners when discussing these issues with patients, together with a
      discussion of the psychological consequences for patients. 

PMID- 25765122
TI  - [Respiratory manifestations of Marfan's syndrome].
AB  - Marfan's syndrome is a rare genetic disorder caused by a mutation of the gene
      FBN1, coding for the protein fibrillin-1. Cardiovascular, musculoskeletal and
      ophthalmic manifestations are the most commonly observed, but minor diagnostic
      criteria also include pulmonary manifestations. Pneumothorax, frequently
      relapsing, affects 5 to 11% of patients. Rib cage abnormalities (pectus excavatum
      or pectus carinatum) and apical blebs may contribute to their occurrence.
      Treatment does not require any specific procedure but there is an increased risk
      of recurrence. Pectus excavatum affects up to 60% of the patients, without any
      functional impairment in most cases. Surgery may be required (using the Nuss
      procedure) in case of cardiovascular or psychological symptoms. Marfan's syndrome
      is frequently associated with obstructive sleep apnoea, which may itself
      contribute to aortic dilatation. Some studies suggest a potential role of
      craniofacial abnormalities in the pathogenesis of sleep apnea in these patients.
      Pulmonologists should consider Marfan's syndrome when treating patients for
      recurrent spontaneous pneumothorax or rib cage abnormalities, since early
      detection of cardiac abnormalities improves the prognosis significantly. 

PMID- 25765124
TI  - Relationship between sleep stages and nocturnal trapezius muscle activity.
AB  - OBJECTIVE: Former studies reported a relationship between increased nocturnal low
      level trapezius muscle activity and neck or shoulder pain but it has not been
      explored whether trapezius muscle relaxation is related to sleep stages. The goal
      of the present study was to investigate whether trapezius muscle activity is
      related to different sleep stages, as measured by polysomnography. METHODS:
      Twenty one healthy subjects were measured on four consecutive nights in their
      homes, whereas the first night served as adaptation night. The measurements
      included full polysomnography (electroencephalography (EEG), electrooculography
      (EOG), electromyography (EMG) and electrocardiography (ECG)), as well as surface
      EMG of the m. trapezius descendens of the dominant arm. RESULTS: Periods with
      detectable EMG activity of the trapezius muscle lasted on average 1.5% of the
      length of the nights and only in four nights it lasted longer than 5% of sleeping
      time. Neither rest time nor the length of periods with higher activity levels of
      the trapezius muscle did significantly differ between sleep stages. CONCLUSIONS:
      We found no evidence that nocturnal trapezius muscle activity is markedly
      moderated by the different sleep stages. Thus the results support that EMG
      measurements of trapezius muscle activity in healthy subjects can be carried out
      without concurrent polysomnographic recordings.

PMID- 25765125
TI  - [New studies question the cardiac safety of conducted electrical weapons].
AB  - Conducted electrical weapons (CEW) were invented in the 1970s and are now widely
      used by more than 16,000 military and law enforcement agencies worldwide. Recent
      studies have sug-gested that a causal relation of cardiac arrest in humans and
      utilization of CEW may exist and cardiac capture and fatal arrhythmia have been
      documented in animal studies. We believe, based on current knowledge, that CEW
      use may have caused human fatalities. Users should be aware of potential serious
      side effects and be able to provide basic life support. 

PMID- 25765123
TI  - Dominant frontotemporal dementia mutations in 140 cases of primary progressive
      aphasia and speech apraxia.
AB  - BACKGROUND: Mutations in three genes [chromosome 9 open-reading-frame 72
      (C9ORF72); microtubule-associated protein tau (MAPT) and progranulin (GRN)]
      account for the vast majority of familial, and a proportion of sporadic,
      frontotemporal dementia (FTD) cases. Progressive apraxia of speech (PAOS) is a
      type of FTD characterized by speech production deficits without a known cause.
      METHODS: We therefore assessed for genetic mutations in C9ORF72, MAPT and GRN in
      40 prospectively recruited PAOS patients. For comparison, we also assessed these
      mutations in 100 patients with primary progressive aphasia (PPA), including
      logopenic PPA (n = 54), nonfluent/agrammatic PPA (n = 17), semantic PPA (n = 16),
      and unclassifiable PPA (n = 13). RESULTS: The mean age at onset of PAOS patients
      was 66.7 years (+/- 9.3); 50% were women. Ten patients (25%) had >=1 first-degree
      relative with a neurodegenerative disease. No mutations were found in any PAOS
      patient. In comparison, 36% of the PPA patients had a family history and 5 (5%)
      had a genetic mutation detected: MAPT (n = 0), GRN (n = 3) and C9ORF72 (n = 2).
      CONCLUSIONS: Although limited by an overrepresentation of logopenic PPA, which
      frequently predicts Alzheimer's disease pathology, this study suggests that
      mutations in the three genes most commonly associated with FTD are not associated
      with PAOS and are not commonly associated with PPA.

PMID- 25765126
TI  - Quantitative evaluation of facial growth in children after unilateral ESS for
      subperiosteal orbital abscess drainage.
AB  - OBJECTIVE: To determine the effects of unilateral endoscopic sinus surgery (ESS)
      on facial skeletal growth in children. DESIGN: Retrospective controlled study.
      SETTING: Academic tertiary referral medical center. MATERIALS AND METHODS:
      Included were children who underwent a unilateral ESS procedure between 1995 and
      2006 to evacuate a subperiosteal orbital abscess (SPOA) and several years later
      went through cephalometric measurements comparing their facial development
      between the surgical and nonsurgical sides. RESULTS: A total of 6 children were
      recruited for this study (3 girls and 3 boys), between the ages 3 to 10 at time
      of surgery, and from 9.5 to 23 years of age today. Four of the children had
      surgery on the right side and 2 on the left. No statistically significant
      difference was found when evaluating all planes in the cephalometric radiographs
      according to age at surgery, age today and years from surgery. CONCLUSION: In our
      study, no significant differences were found in craniofacial growth between the
      sides of the face in children who underwent ESS for the same medical indication
      on one side of the face, suggesting that ESS might be safely performed even in
      young children. LEVEL OF EVIDENCE: -2c.

PMID- 25765127
TI  - Salivary glands of healthy children versus sialorrhea children, is there an
      anatomical difference? An ultrasonographic biometry.
AB  - OBJECTIVES: There is no literature about the average size of the salivary glands
      in the pediatric population with drooling (sialorrhea). Studies have shown that
      some pathologies affect the functionality of the salivary glands. We assessed via
      ultrasonography the sizes of the submandibular and parotid glands in 9 healthy
      children who were not suffering from local or systemic diseases that could affect
      the salivary glands. We also compared this group with a group of 9 patients with
      sialorrhea. METHODS: Volunteers were matched based on age, gender, and BMI. Body
      weight did not differ more than 20% from ideal weight. The parotid and
      submandibular glands of 9 patients with sialorrhea without any previous treatment
      were measured via ultrasound and matched to a healthy control. Children with
      various causes for drooling were included (neurological disorders, neuromuscular
      disorders, lack of oral motor control). RESULTS: Dimensions of the parotid glands
      in drooling and healthy patients were: surface area 2.96 cm(2) (SD +/-0.90) and
      2.81 cm(2) (SD +/-0.54); in depth 1.68 cm (SD +/-0.24) and 1.61 cm (SD +/-0.27);
      in the axis longitudinal to the horizontal mandibular ramus 3.18 cm (+/-0.46) and
      3.15 cm (SD +/-0.45) in drooling and healthy groups respectively. The means of
      submandibular glands of drooling and healthy patients measured in surface area:
      3.20 cm(2) (SD +/-0.66) and 3.08 cm(2) (SD +/-0.65); anterior-posterior length
      1.55 cm (SD +/-0.23) and 1.46 cm (SD +/-0.23), medio-lateral length 3.07 cm (SD
      +/-0.39) and 3.07 cm (SD +/-0.32). There was no statistical significance in
      comparison with the healthy group control. CONCLUSION: The parotid and
      submandibular salivary glands in the pediatric population do not differ in size
      in children with or without drooling. Measuring the glands at baseline and post
      treatment with botulinum toxin injections allows one to evaluate if there are
      changes in the gland related to the treatment.

PMID- 25765128
TI  - Outpatient rehabilitation care process factors and clinical outcomes among
      patients discharged home following unilateral total knee arthroplasty.
AB  - Research examining care process variables and their relationship to clinical
      outcomes after total knee arthroplasty has focused primarily on inpatient
      variables. Care process factors related to outpatient rehabilitation have not
      been adequately examined. We conducted a retrospective review of 321 patients
      evaluating outpatient care process variables including use of continuous passive
      motion, home health physical therapy, number of days from inpatient discharge to
      beginning outpatient physical therapy, and aspects of outpatient physical therapy
      (number of visits, length of stay) as possible predictors of pain and disability
      outcomes of outpatient physical therapy. Only the number of days between
      inpatient discharge and outpatient physical therapy predicted better outcomes,
      suggesting that this may be a target for improving outcomes after total knee
      arthroplasty for patients discharged directly home. 

PMID- 25765129
TI  - Outcomes Following Primary Total Hip or Knee Arthroplasty in Substance Misusers.
AB  - The influence of drug misuse on outcomes following primary total hip (THA) or
      knee (TKA) arthroplasty is poorly understood. The National Hospital Discharge
      Survey was used to identify patients who underwent primary THA or TKA between
      1990 and 2007. Patients were divided into two groups: 1) those with a diagnosis
      of drug misuse (cannabis, opioids, cocaine, amphetamines, sedatives, inhalants or
      mixed combinations) (n=13,163) and 2) those with no diagnosis of misuse
      (n=8,366,327). Patients with a diagnosis of drug misuse had longer hospital stays
      (P<0.001), nearly eight times the odds of leaving against medical advice
      (P<0.001) and five times the mortality rate (P<0.001). Drug misuse was associated
      with higher odds (P<0.001) of complications including postoperative infection,
      anemia, convulsions, osteomyelitis, and blood transfusion. 

PMID- 25765130
TI  - Prevalence and Costs of Rehabilitation and Physical Therapy After Primary TJA.
AB  - This study evaluated the trends in discharge patterns and the prevalence and cost
      of post-discharge PT. The 5% Medicare database (1997-2010) was used to identify
      50,886 primary THA and 107,675 TKA patients. More than 50% of patients were
      discharged from hospital to an inpatient facility. There were an increase in
      discharges to skilled nursing units and a reduced rate to rehabilitation
      facilities. In contrast to hospital, surgeon reimbursement, and implant costs,
      the average annual PT cost per patient rose through the study period.
      Approximately 25% of PT costs were used on less common modalities. PT costs more
      than $648 million a year. With the increased pressure to control costs for
      primary TJA, these patterns may change unless PT effectiveness can be
      demonstrated. 

PMID- 25765132
TI  - Performance of Porous Tantalum vs. Titanium Cup in Total Hip Arthroplasty:
      Randomized Trial with Minimum 10-Year Follow-Up.
AB  - Porous tantalum monoblock cups have been proposed to improve survivorship of
      cementless primary THA. However, there are few direct comparative trials to
      established implants such as porous-coated titanium cups. 113 patients were
      randomized into two groups according to the cup: a porous tantalum monoblock cup
      (TM) or a porous-coated titanium monoblock cup (control). At a mean of 12 years
      after THA, no implants migrated in both groups. Two TM patients (4%) and 13
      control patients (33%) presented with radiolucency around the cup (P<0.001). In
      the control group, 1 cup (2%) was revised for aseptic loosening. At 12 years post
      implantation, porous tantalum monoblock cups demonstrated 100% survivorship, and
      significantly less radiolucency as compared to porous-coated titanium monoblock
      cups. 

PMID- 25765131
TI  - Intraoperative Periprosthetic Femur Fracture: A Biomechanical Analysis of
      Cerclage Fixation.
AB  - Intraoperative periprosthetic femur fracture is a known complication of total hip
      arthroplasty (THA) and a variety of cerclage systems are available to manage
      these fractures. The purpose of this study was to examine the in situ
      biomechanical response of cerclage systems for fixation of periprosthetic femur
      fractures that occur during cementless THA. We compared cobalt chrome (CoCr)
      cables, synthetic cables, monofilament wires and hose clamps under axial
      compressive and torsional loading. Metallic constructs with a positive locking
      system performed the best, supporting the highest loads with minimal implant
      subsidence (both axial and angular) after loading. Overall, the CoCr cable and
      hose clamp had the highest construct stiffness and least reduction in stiffness
      with increased loading. They were not demonstrably different from each other. 

PMID- 25765133
TI  - Extrapolating histone marks across developmental stages, tissues, and species: an
      enhancer prediction case study.
AB  - BACKGROUND: Dynamic activation and inactivation of gene regulatory DNA produce
      the expression changes that drive the differentiation of cellular lineages.
      Identifying regulatory regions active during developmental transitions is
      necessary to understand how the genome specifies complex developmental programs
      and how these processes are disrupted in disease. Gene regulatory dynamics are
      mediated by many factors, including the binding of transcription factors (TFs)
      and the methylation and acetylation of DNA and histones. Genome-wide maps of TF
      binding and DNA and histone modifications have been generated for many cellular
      contexts; however, given the diversity and complexity of animal development,
      these data cover only a small fraction of the cellular and developmental contexts
      of interest. Thus, there is a need for methods that use existing epigenetic and
      functional genomics data to analyze the thousands of contexts that remain
      uncharacterized. RESULTS: To investigate the utility of histone modification data
      in the analysis of cellular contexts without such data, I evaluated how well
      genome-wide H3K27ac and H3K4me1 data collected in different developmental stages,
      tissues, and species were able to predict experimentally validated heart
      enhancers active at embryonic day 11.5 (E11.5) in mouse. Using a machine-learning
      approach to integrate the data from different contexts, I found that E11.5 heart
      enhancers can often be predicted accurately from data from other contexts, and I
      quantified the contribution of each data source to the predictions. The utility
      of each dataset correlated with nearness in developmental time and tissue to the
      target context: data from late developmental stages and adult heart tissues were
      most informative for predicting E11.5 enhancers, while marks from stem cells and
      early developmental stages were less informative. Predictions based on data
      collected in non-heart tissues and in human hearts were better than random, but
      worse than using data from mouse hearts. CONCLUSIONS: The ability of these
      algorithms to accurately predict developmental enhancers based on data from
      related, but distinct, cellular contexts suggests that combining computational
      models with epigenetic data sampled from relevant contexts may be sufficient to
      enable functional characterization of many cellular contexts of interest.

PMID- 25765134
TI  - Adaptive contraction of diet breadth affects sexual maturation and specific
      nutrient consumption in an extreme generalist omnivore.
AB  - Animals balance their intake of specific nutrients, but little is known about how
      they do so when foraging in an environment with toxic resources and whether toxic
      foods promote adaptations that affect life history traits. In German cockroach
      (Blattella germanica) populations, glucose aversion has evolved in response to
      glucose-containing insecticidal baits. We restricted newly eclosed glucose-averse
      (GA) and wild-type (WT) female cockroaches to nutritionally defined diets varying
      in protein-to-carbohydrate (P : C) ratio (3 : 1, 1 : 1, or 1 : 3) or gave them
      free choice of the 3 : 1 and 1 : 3 diets, with either glucose or fructose as the
      sole carbohydrate source. We measured consumption of each diet over 6 days and
      then dissected the females to measure the length of basal oocytes in their
      ovaries. Our results showed significantly lower consumption by GA compared to WT
      cockroaches when restricted to glucose-containing diets, but also lower fructose
      intake by GA compared to WT cockroaches when restricted to high fructose diets or
      given choice of fructose-containing diets. Protein intake was regulated tightly
      regardless of carbohydrate intake, except by GA cockroaches restricted to glucose
      containing diets. Oocyte growth was completely suppressed in GA females
      restricted to glucose-containing diets, but also significantly slower in GA than
      in WT females restricted to fructose-containing diets. Our findings suggest that
      GA cockroaches have adapted to reduced diet breadth through endocrine adjustments
      which reduce requirements for energetic fuels. Our study illustrates how an
      evolutionary change in the chemosensory system may affect the evolution of other
      traits that govern animal life histories.

PMID- 25765135
TI  - Quality management in European screening laboratories in blood establishments: A
      view of current approaches and trends.
AB  - The screening laboratory has a critical role in the post-transfusion safety. The
      success of its targets and efficiency depends on the management system used. Even
      though the European Union directive 2002/98/EC requires a quality management
      system in blood establishments, its requirements for screening laboratories are
      generic. Complementary approaches are needed to implement a quality management
      system focused on screening laboratories. This article briefly discusses the
      current good manufacturing practices and good laboratory practices, as well as
      the trends in quality management system standards. ISO 9001 is widely accepted in
      some European Union blood establishments as the quality management standard,
      however this is not synonymous of its successful application. The ISO "risk-based
      thinking" is interrelated with the quality risk-management process of the EuBIS
      "Standards and criteria for the inspection of blood establishments". ISO 15189
      should be the next step on the quality assurance of a screening laboratory, since
      it is focused on medical laboratory. To standardize the quality management
      systems in blood establishments' screening laboratories, new national and
      European claims focused on technical requirements following ISO 15189 is needed. 

PMID- 25765136
TI  - Robust high-throughput batch screening method in 384-well format with optical in
      line resin quantification.
AB  - High-throughput batch screening technologies have become an important tool in
      downstream process development. Although continuative miniaturization saves time
      and sample consumption, there is yet no screening process described in the 384
      well microplate format. Several processes are established in the 96-well
      dimension to investigate protein-adsorbent interactions, utilizing between 6.8
      and 50 MUL resin per well. However, as sample consumption scales with resin
      volumes and throughput scales with experiments per microplate, they are limited
      in costs and saved time. In this work, a new method for in-well resin
      quantification by optical means, applicable in the 384-well format, and resin
      volumes as small as 0.1 MUL is introduced. A HTS batch isotherm process is
      described, utilizing this new method in combination with optical sample volume
      quantification for screening of isotherm parameters in 384-well microplates.
      Results are qualified by confidence bounds determined by bootstrap analysis and a
      comprehensive Monte Carlo study of error propagation. This new approach opens the
      door to a variety of screening processes in the 384-well format on HTS stations,
      higher quality screening data and an increase in throughput.

PMID- 25765137
TI  - [Unusual lymphangitis].

PMID- 25765138
TI  - [A unusual brain cortical tumor: angiocentric glioma].
AB  - We report the case of an 11-year-old girl, who was admitted for surgery of an
      epilepsy-associated brain tumor. The radiological and clinical hypothesis was
      dysembryoplasic neuroepithelial tumor. Histopathological examination revealed a
      tumoral proliferation composed of spindle-shaped cells with palisade arrangements
      around vessels. Tumor cells have small, round and regular nuclei without atypia
      or mitosis. On immunohistochemistry, the neoplastic cells strongly expressed GFAP
      and showed a characteristic cytoplasmic dot-like staining with EMA (epithelial
      membrane antigen). Ki-67 labeling index was low. Molecular analysis failed to
      reveal the V600E mutation of BRAF gene. The patient was free of seizures after
      surgery. Angiocentric glioma is a rare brain tumor occuring preferably in
      children and young adults and is associated with seizures. The precise
      histogenesis remains debated. The treatment of choice is total resection. The
      prognosis is favorable if totally resected. 

PMID- 25765139
TI  - [An important pyloric wall thickening in an adult].

PMID- 25765140
TI  - [A peritoneal nodule like no other!].

PMID- 25765141
TI  - [A terrible endoscopy].

PMID- 25765142
TI  - [An unusual calculous chronic cholecystitis].

PMID- 25765143
TI  - The most frequent cause of 90-day unplanned hospital readmission following
      colorectal cancer resection is chemotherapy complications.
AB  - AIM: NHS England deems 90-day readmission rates as a marker of quality of care.
      The causes of readmission have not been previously reported in the UK. The aim of
      this study was to examine the factors associated with 90-day readmission
      following colorectal cancer surgery at a hospital trust with a catchment
      population 1.2 million. METHOD: A retrospective review was performed of all
      patients undergoing resection for colorectal cancer between January 2012 and
      December 2013. Unplanned readmission was defined as an emergency admission to the
      trust for any cause within 90 days of surgery. Readmission analyses were
      restricted to patients discharged from hospital within 28 days of resection.
      RESULTS: A total of 570 patients underwent surgery, of whom 522 were discharged
      within 28 days and are included for readmission analysis. The readmission rate
      was 24.3% (127 patients with a total of 163 episodes of hospital readmissions)
      within 90 days following surgery. The most frequent cause for readmission was
      complications related to adjuvant chemotherapy (18.4%) followed by wound-related
      complications (14.1%). Most patients presenting with wound-related complications
      were admitted within 60 days and patients with chemotherapy-related complications
      after 61 days; 13/127 (10.2%) patients who were readmitted underwent emergency
      surgery, and one patient died following readmission. Multivariate analysis
      demonstrated that comorbidity was the only independent risk factor. CONCLUSION:
      Ninety-day readmissions include a high number of readmissions secondary to
      chemotherapy-related complications, whereas most surgical-related readmission
      present within 60 days.

PMID- 25765144
TI  - Evaluating psychological interventions in a novel experimental human model of
      anxiety.
AB  - Inhalation of 7.5% carbon dioxide increases anxiety and autonomic arousal and
      provides a novel experimental model of anxiety with which to evaluate
      pharmacological and psychological treatments for anxiety. To date several
      psychotropic drugs including benzodiazepines, SSRIs and SNRIs have been evaluated
      using the 7.5% CO2 model; however, it has yet to be used to evaluate
      psychological interventions. We compared the effects of two core psychological
      components of mindfulness-meditation (open monitoring and focused attention)
      against general relaxation, on subjective, autonomic and neuropsychological
      outcomes in the 7.5% CO2 experimental model. 32 healthy screened adults were
      randomized to complete 10 min of guided open monitoring, focused attention or
      relaxation, immediately before inhaling 7.5% CO2 for 20 min. During CO2-challenge
      participants completed an eye-tracking measure of attention control and selective
      attention. Measures of subjective anxiety, blood pressure and heart rate were
      taken at baseline and immediately following intervention and CO2-challenge. OM
      and FA practice reduced subjective feelings of anxiety during 20-min inhalation
      of 7.5% CO2 compared to relaxation control. OM practice produced a strong
      anxiolytic effect, whereas the effect of FA was more modest. Anxiolytic OM and FA
      effects occurred in the absence of group differences in autonomic arousal and eye
      movement measures of attention. Our findings are consistent with
      neuropsychological models of mindfulness-meditation that propose OM and FA
      activate prefrontal mechanisms that support emotion regulation during periods of
      anxiety and physiological hyper-arousal. Our findings complement those from
      pharmacological treatment studies, further supporting the use of CO2 challenge to
      evaluate future therapeutic interventions for anxiety. 

PMID- 25765145
TI  - Dietary L-methionine restriction decreases oxidative stress in porcine liver
      mitochondria.
AB  - Dietary methionine restriction (MetR) has been reported to improve hepatocyte
      function in mammals. However, the underlying mechanisms remain largely unknown.
      This study was conducted with a swine model to test the hypothesis that MetR
      decreases generation of reactive oxygen species (ROS) and attenuates oxidative
      damage in hepatic mitochondria. Twenty-four 35-day old pigs were fed a control
      diet or a Met-restricted diet for two weeks. Liver mitochondria were isolated to
      determine: 8-oxodG in mitochondrial DNA, oxidative-derived proteins markers,
      including glutamic semialdehyde (GSA), aminoadipic semialdehydes (AASA),
      carboxyethyl-lysine (CEL), carboxymethyl-lysine (CML), and malondialdehyde lysine
      (MDAL), mitochondrial H2O2 generation rate; rates of oxygen consumption; free
      radical leak (FRL); anti-oxidative capacity, electron transport complex activity;
      and protein abundances of respiratory chain complex subunits (NDUFA9, SDHA, Core
      2, and Cox 1), manganese superoxide dismutase (MnSOD), and apoptosis-inducing
      factor (AIF). Compared with the control, MetR decreased mitochondrial 8-oxodG
      content, H2O2 generation, FRL (P<0.05), and increased rates of oxygen
      consumption. Abundances of markers for protein oxidative damage, including GSA,
      AASA, CEL, and CML, were decreased (P<0.05) by 40%, 30%, 32%, and 28%,
      respectively, compared with the control. Western blot analysis revealed that MetR
      decreased (P<0.05) the protein abundances of complex subunits, NDUFA9 and AIF
      without affecting expression of SDHA, Core 2, Cox 1 or MnSOD. The complex I
      activity (P<0.05) were lowered in MetR group as compared with that of control.
      Collectively, our findings indicate that dietary MetR decreases mitochondrial ROS
      generation primarily via inhibiting complex I activity and ROS generation rather
      than augmenting anti-oxidative capacity, thereby ameliorating oxidative damage to
      hepatic mitochondrial DNA and proteins. 

PMID- 25765146
TI  - Optimized microRNA purification from TRIzol-treated plasma.
AB  - BACKGROUND: MicroRNAs (miRNAs) represent new and potentially informative
      diagnostic targets for disease detection and prognosis. However, little work
      exists documenting the effect of TRIzol, a common viral inactivation and nucleic
      acid extraction reagent, on miRNA purification. Here, we developed an optimized
      protocol for miRNA extraction from plasma samples by evaluating five different
      RNA extraction kits, TRIzol phase separation, purification additives, and initial
      plasma sample volume. This method was then used for downstream profiling of
      plasma miRNAs found in archived samples from one nonhuman primate (NHP)
      experimentally challenged with Ebola virus by the aerosol route. RESULTS:
      Comparison of real-time RT-PCR results for spiked-in and endogenous miRNA
      sequences determined extraction efficiencies from five different RNA purification
      kits. These experiments showed that 50 MUL plasma processed using the QIAGEN
      miRNeasy Mini Kit with 5 MUg of glycogen as a co-precipitant yielded the highest
      recovery of endogenous miRNAs. Using this optimized protocol, miRNAs from
      archived plasma samples of one rhesus macaque challenged with aerosolized Ebola
      virus was profiled using a targeted real-time PCR array. A total of 519 of the
      752 unique miRNAs assayed were present in the plasma samples at day 0 and day 7
      (time of death) post-exposure. Statistical analyses revealed 25 sequences
      significantly up- or down-regulated between day 0 and day 7 post infection,
      validating the utility of the extraction method for plasma miRNA profiling.
      CONCLUSIONS: This study contributes to the knowledgebase of circulating miRNA
      extraction methods and expands on the potential applications of cell-free miRNA
      profiling for diagnostics and pathogenesis studies. Specifically, we optimized an
      extraction protocol for miRNAs from TRIzol-inactivated plasma samples that can be
      used for highly pathogenic viruses.

PMID- 25765147
TI  - Radiation Therapy to the Plexus Brachialis in Breast Cancer Patients: Analysis of
      Paresthesia in Relation to Dose and Volume.
AB  - PURPOSE: To identify volume and dose predictors of paresthesia after irradiation
      of the brachial plexus among women treated for breast cancer. METHODS AND
      MATERIALS: The women had breast surgery with axillary dissection, followed by
      radiation therapy with (n=192) or without irradiation (n=509) of the
      supraclavicular lymph nodes (SCLNs). The breast area was treated to 50 Gy in 2.0
      Gy fractions, and 192 of the women also had 46 to 50 Gy to the SCLNs. We
      delineated the brachial plexus on 3-dimensional dose-planning computerized
      tomography. Three to eight years after radiation therapy the women answered a
      questionnaire. Irradiated volumes and doses were calculated and related to the
      occurrence of paresthesia in the hand. RESULTS: After treatment with axillary
      dissection with radiation therapy to the SCLNs 20% of the women reported
      paresthesia, compared with 13% after axillary dissection without radiation
      therapy, resulting in a relative risk (RR) of 1.47 (95% confidence interval [CI]
      1.02-2.11). Paresthesia was reported by 25% after radiation therapy to the SCLNs
      with a V40 Gy >= 13.5 cm(3), compared with 13% without radiation therapy, RR 1.83
      (95% CI 1.13-2.95). Women having a maximum dose to the brachial plexus of >=55.0
      Gy had a 25% occurrence of paresthesia, with RR 1.86 (95% CI 0.68-5.07, not
      significant). CONCLUSION: Our results indicate that there is a correlation
      between larger irradiated volumes of the brachial plexus and an increased risk of
      reported paresthesia among women treated for breast cancer.

PMID- 25765148
TI  - Comparison of modified Chicago sky blue stain and potassium hydroxide mount for
      the diagnosis of dermatomycoses and onychomycoses.
AB  - The diagnostic value of modified Chicago sky blue (CSB) stain and potassium
      hydroxide (KOH) mount for superficial mycoses was compared using fungal culture
      as gold standard. The sensitivity and screening time of the CSB stain were
      superior to the KOH mount. The CBS stain is simple, quick and reliable for
      diagnosing superficial mycoses. 

PMID- 25765149
TI  - Evaluation of matrix-assisted laser desorption ionization-time-of-flight mass
      spectrometry for species identification of nonfermenting Gram-negative bacilli.
AB  - Matrix-assisted laser desorption ionization-time-of-flight mass spectrometry
      (MALDI-TOF MS) to identify 396 Nonfermenting Gram-Negative Bacilli clinical
      isolates was evaluated in comparison with conventional phenotypic tests and/or
      molecular methods. MALDI-TOF MS identified to species level 256 isolates and to
      genus or complex level 112 isolates. It identified 29 genera including uncommon
      species. 

PMID- 25765150
TI  - Numerical solution of a microbial growth model applied to dynamic environments.
AB  - The Baranyi and Roberts model is one of the most frequently used microbial growth
      models. It has been successfully applied to numerous studies of various
      microorganisms in different food products. Under dynamic conditions, the model is
      implicitly formulated as a set of two coupled differential equations which could
      be numerically solved using the Runge-Kutta method. In this study, a simplified
      numerical solution of the coupled differential equations was derived and used to
      simulate microbial growth under dynamic conditions in Microsoft Excel. As
      expected, the results obtained were the same as those from solving the coupled
      differential equations using a MATLAB Solver. In addition, model parameters were
      accurately identified by fitting the numerical solution to simulated growth
      curves under dynamic (time-varying) temperature conditions using the Microsoft
      Excel Solver. 

PMID- 25765151
TI  - Feasibility and Safety of MR-Guided Focused Ultrasound Lesioning in the Setting
      of Deep Brain Stimulation.
AB  - BACKGROUND: Patients treated with deep brain stimulation (DBS) often develop
      symptom progression. If safe, focused ultrasound (FUS) lesioning could be used
      for patients unable to undergo further DBS surgery. OBJECTIVE: To test the
      feasibility and safety of MR-guided FUS surgery in the setting of a previously
      implanted DBS system. METHODS: Three preclinical experiments were designed to
      test feasibility and safety. Hydrogels were implanted with an electrode, and FUS
      lesions were targeted adjacently. Cadavers were implanted with a thalamic
      electrode, and FUS lesions were targeted in the contralateral thalamus. Finally,
      DBS systems were implanted in swine, and FUS lesioning was targeted to the
      contralateral thalamus, MRI was used to assess the treatments, and histological
      analyses were performed at 2 days and at 1 month. RESULTS: In gel experiments and
      cadavers, FUS resulted in target heating to 29-32 degrees C without any heating
      at the electrode. In animal experiments, there were no FUS-related MRI signal
      changes near the electrode. Histological analysis showed typical FUS lesions with
      no evidence of damage surrounding the electrode tracts. CONCLUSIONS: FUS is
      feasible in the setting of a preimplanted DBS device. There was minimal heating
      of the device during the procedure and no apparent FUS-related tissue injury. (c)
      2015 S. Karger AG, Basel.

PMID- 25765152
TI  - A structural model for FOXRED1, an FAD-dependent oxidoreductase necessary for
      NADH: Ubiquinone oxidoreductase (complex I) assembly.
AB  - The biogenesis of mitochondrial respiratory chain components is complex.
      Mammalian complex I (NADH:ubiquinone oxidoreductase) contains 44 different
      subunits, an FMN and seven iron-sulfur centers. Its assembly involves at least
      twelve additional proteins, called assembly factors. One of these is FOXRED1, a
      486-amino acid FAD-dependent oxidoreductase. FOXRED1 is a member of the d-amino
      acid oxidase (DAO) family. A structural model of FOXRED1 reveals a large
      substrate-binding cavity and a putative oxygen-binding site. These features
      strongly suggest that FOXRED1 is catalytically active as an oxidoreductase. A
      metabolic role for FOXRED1 in the biogenesis of complex I should be considered. 

PMID- 25765153
TI  - Mutation loads in different tissues from six pathogenic mtDNA point mutations.
AB  - In this work, we studied the mtDNA mutations m.3243A>G, m.3252A>G, m.15923A>G,
      m.13513G>A, m.8993T>G and m.9176T>C in the blood, urine and buccal mucosa of a
      cohort of 27 subjects. Urine cells had the highest mutation load for all of the
      mtDNA mutations studied. The mutation loads in the blood, urine and the buccal
      mucosa were significantly higher in the mitochondrial disorder group that
      manifested clinical signs than in the asymptomatic subjects. In conclusion, urine
      is a suitable biological sample for molecular diagnosis of mtDNA mutations and
      for the study of the attendant risk of recurrence in the offspring of
      asymptomatic mothers identified as non-carriers after mutation analysis in blood.

PMID- 25765154
TI  - Single mechanically-gated cation channel currents can trigger action potentials
      in neocortical and hippocampal pyramidal neurons.
AB  - The mammalian brain is a mechanosensitive organ that responds to different
      mechanical forces ranging from intrinsic forces implicated in brain morphogenesis
      to extrinsic forces that can cause concussion and traumatic brain injury.
      However, little is known of the mechanosensors that transduce these forces. In
      this study we use cell-attached patch recording to measure single mechanically
      gated (MG) channel currents and their affects on spike activity in identified
      neurons in neonatal mouse brain slices. We demonstrate that both neocortical and
      hippocampal pyramidal neurons express stretch-activated MG cation channels that
      are activated by suctions of ~25mm Hg, have a single channel conductance for
      inward current of 50-70pS and show weak selectivity for alkali metal cations
      (i.e., Na(+)<K(+)<Cs(+)). Significantly, single MG channel currents activated on
      the soma trigger spiking/action potentials in both neocortical and hippocampal
      pyramidal neurons. Not all neuron types studied here expressed MG channel
      currents. In particular, locus coeruleus and cerebellar Purkinje neurons showed
      no detectable MG channel activity. Moreover their robust rhythmic spike activity
      was resistant to mechanical modulation. Our observation that a single MG channel
      current can trigger spiking predicates the need for reassessment of the long held
      view that the impulse output of central neurons depends only upon their intrinsic
      voltage-gated channels and/or their integrated synaptic input. 

PMID- 25765156
TI  - Priming with threatening faces modulates the self-face advantage by enhancing the
      other-face processing rather than suppressing the self-face processing.
AB  - Social emotional information influences self-processing in everyday activities,
      but few researchers have investigated this process. The current ERP study adopted
      a prime paradigm to investigate how socially threatening faces impact on the self
      face processing advantage. After being primed with emotional faces (happy, angry
      or neutral), participants judged whether the target face (self, friend, and
      stranger) was familiar or unfamiliar. Results showed an interaction effect
      between the prime face and the target face at posterior P3, suggesting that after
      priming with happy and neutral faces, self-faces elicited larger P3 amplitudes
      than friend-faces and stranger-faces; however, after priming with angry faces,
      the P3 amplitudes were not significantly different between self-face and friend
      face. Moreover, the P3 amplitudes of self-faces did not differ between priming
      with angry and neutral faces; however, the P3 amplitude of both friend-faces and
      stranger-faces showed enhanced responses after priming with angry faces compared
      to priming with neutral faces. We suggest that the self-face processing advantage
      (self vs. friend) could be weakened by priming with threatening faces, through
      enhancement of the other-faces processing rather than suppression of self-faces
      processing in angry vs. neutral face prime. 

PMID- 25765155
TI  - Erythropoietin negatively regulates pituitary ACTH secretion.
AB  - Erythropoietin (Epo) and Epo-receptor (EpoR) signaling, in addition to its
      classical role in erythropoiesis, exhibit a protective response in non
      hematopoietic tissues. Mice with EpoR expression restricted to only hematopoietic
      tissues (DeltaEpoRE), become obese, have low energy expenditure, and are glucose
      intolerant and insulin resistant. In the arcuate nucleus of the mouse
      hypothalamus, EpoR expression co-localizes in proopiomelanocortin (POMC) neurons.
      In vivo high-dose Epo treatment increases hypothalamus POMC, reduces food intake
      and fat mass accumulation. Here we report that Epo treatment also decreases
      plasma concentration of the pituitary derived POMC peptide, adrenocorticotropic
      hormone (ACTH). Conversely, DeltaEpoRE mice show reduced hypothalamus POMC and
      high plasma concentrations of ACTH. In the pituitary, POMC is synthesized in the
      corticotroph cells, and here we examine Epo effect on pituitary POMC expression
      using the AtT-20 mouse corticotroph pituitary cell line. In AtT-20 cells, enzyme
      immunoassay analysis showed that Epo inhibits ACTH secretion. This effect is post
      translational, as Epo treatment did not affect POMC mRNA expression but increased
      intracellular levels of ACTH peptide. Moreover, Epo reduced the basal
      intracellular calcium (Ca(2+)) levels, suggesting an effect in the Ca(2+)
      signaling pathway. In summary, our studies suggest a novel regulatory pathway of
      ACTH secretion in the pituitary via EpoR-signaling. The higher plasma ACTH level
      in DeltaEpoRE mice also suggests a possible mechanism of deregulated pituitary
      function with loss of Epo-signaling. 

PMID- 25765157
TI  - Sensorimotor skills in Fxn KO/Mck mutants deficient for frataxin in muscle.
AB  - Friedreich ataxia is the most common autosomal recessive disorder of the
      cerebellum, causing degeneration of spinal sensory neurons and spinocerebellar
      tracts. The disease is caused by severely reduced levels of frataxin, a
      mitochondrial protein involved in iron metabolism. An experimental model has been
      generated by crossing mice homozygous for a conditional allele of the Fxn gene
      with mice heterozygous for a deleted exon 4 of Fxn carrying a tissue-specific Cre
      transgene under control of the muscle creatine kinase promoter. Relative to wild
      type, Fxn null mutants were impaired on tests of motor coordination comprising
      horizontal bar, vertical pole, and the rotorod as well as displaying gait
      anomalies and the hindlimb clasping response. The Fxn KO/Mck model reproduces
      some key features of patients with Friedreich ataxia and provides an opportunity
      of ameliorating their symptoms with experimental therapies. 

PMID- 25765158
TI  - Component-resolved IgE profiles in Austrian patients with a convincing history of
      peanut allergy.
AB  - BACKGROUND: Peanut allergy develops after primary sensitization to peanut
      allergens and/or IgE cross-sensitization with homologous allergens from various
      plants. Therefore, heterogeneous patterns of sensitization to individual peanut
      allergens are observed in different countries. The aim of this study was to
      examine the IgE sensitization patterns of Austrian peanut-allergic patients.
      METHODS: Sera from 65 peanut-allergic patients and 20 peanut-tolerant atopics
      were obtained in four Austrian allergy clinics. Sensitization patterns against
      peanut allergens Ara h 1-3, 6, 8 and 9 were identified by ImmunoCAP and ImmunoCAP
      ISAC. RESULTS: Austrian peanut-allergic patients were sensitized to Ara h 2 and 6
      (71%), followed by Ara h 1 (62%), Ara h 8 (45%), Ara h 3 (35%) and Ara h 9 (11%).
      All sera containing Ara h 2-specific IgE were also positive for Ara h 6, with Ara
      h 6-specific IgE levels significantly (p < 0.05) higher compared with Ara h 2.
      Twelve percent displayed IgE reactivity exclusively to Ara h 8. Peanut extract
      and Ara h 8 showed low diagnostic specificities of 25 and 10%, respectively. The
      other peanut allergens showed 100% specificity. Diagnostic sensitivities
      determined by ImmunoCAP ISAC and ImmunoCAP were highly similar for Ara h 2, 3 and
      8. CONCLUSIONS: The majority of symptomatic peanut-allergic patients are
      sensitized to Ara h 2 and Ara h 6. In peanut-symptomatic patients with additional
      birch pollen allergy, other peanut allergens, especially Ara h 8, should be
      tested when IgE reactivity to Ara h 2 is absent.

PMID- 25765159
TI  - Phytochip: development of a DNA-microarray for rapid and accurate identification
      of Pseudo-nitzschia spp and other harmful algal species.
AB  - Detection of harmful algal blooms has become a challenging concern because of the
      direct impacts on public health and economy. The identification of toxic
      dinoflagellates and diatoms in monitoring programs requires an extensive
      taxonomic expertise and is time consuming. Advances in molecular biology have
      allowed the development of new approaches, more rapid, accurate and cost
      effective for detecting these microorganisms. In this context, we developed a new
      DNA microarray (called, Phytochip) for the simultaneous detection of multiple HAB
      species with a particular emphasis on Pseudo-nitzschia species. Oligonucleotide
      probes were designed along the rRNA operon. After DNA extraction, the target rDNA
      genes were amplified and labeled using an asymmetric PCR; then, the amplicons
      were hybridized to the oligonucleotide probes present on the chips. The total
      assay from seawater sampling to data acquisition can be performed within a
      working day. Specificity and sensitivity were assessed by using monoclonal
      cultures, mixtures of species and field samples spiked with a known amount of
      cultured cells. The Phytochip with its 81 validated oligonucleotide probes was
      able to detect 12 species of Pseudo-nitzschia and 11 species of dinoflagellates
      among which were 3 species of Karenia and 3 species of Alexandrium. The Phytochip
      was applied to environmental samples already characterized by light microscopy
      and cloned into DNA libraries. The hybridizations on the Phytochip were in good
      agreement with the sequences retrieved from the clone libraries and the
      microscopic observations. The Phytochip enables a reliable multiplex detection of
      phytoplankton and can assist a water quality monitoring program as well as more
      general ecological research. 

PMID- 25765161
TI  - Measuring success in obesity prevention: a synthesis of Health Promotion
      Switzerland's long-term monitoring and evaluation strategy.
AB  - AIMS: Since 2007, Health Promotion Switzerland has implemented a national
      priority program for a healthy body weight. This article provides insight into
      the methodological challenges and results of the program evaluation. METHODS:
      Evaluation of the long-term program required targeted monitoring and evaluation
      projects addressing different outcome levels. The evaluation was carried out
      according to the Swiss Model for Outcome Classification (SMOC), a model designed
      to classify the effects of health promotion and prevention efforts. RESULTS: The
      results presented in this article emphasize both content and methods. The
      national program successfully achieved outcomes on many different levels within
      complex societal structures. The evaluation system built around the SMOC enabled
      assessment of program progress and the development of key indicators. However, it
      is not possible to determine definitively to what extent the national program
      helped stabilize the prevalence of obesity in Switzerland. CONCLUSION: The model
      has shown its utility in providing a basis for evaluation and monitoring of the
      national program. Continuous analysis of data from evaluation and monitoring has
      made it possible to check the plausibility of suspected causal relationships as
      well as to establish an overall perspective and assessment of effectiveness
      supported by a growing body of evidence.

PMID- 25765160
TI  - Association of peripheral total and differential leukocyte counts with obesity
      related complications in young adults.
AB  - OBJECTIVE: Obesity has been demonstrated to be associated with elevated
      leukocytes in adults and children. This study assessed the associations between
      peripheral total and differential leukocyte counts and obesity-related
      complications in young adults. METHODS: 12 obese (median age 21.5 (range 19-28)
      years, median BMI 35.7 (range 32.0-44.9) kg/m(2)) and 11 normal (median age 23
      (range 18-27) years, median BMI 19.5 (range 18.1-21.7) kg/m(2)) adults were
      enrolled. Complete blood count and serum levels of liver enzymes, fasting blood
      glucose, insulin and lipids were measured, and the homeostasis model assessment
      of insulin resistance was calculated. Fat mass was calculated using a
      bioimpedance analysis device, and ultrasonography was performed to measure fat
      thickness and to detect fatty change of the liver. RESULTS: Total leukocyte and
      monocyte counts were significantly increased in obese young adults. Total
      leukocyte count was associated with liver enzyme levels, insulin resistance as
      well as visceral and subcutaneous fat thickness. Neutrophil count was associated
      with insulin resistance. Lymphocyte count was associated with serum liver
      enzymes, insulin resistance, and dyslipidemia. Monocyte count was associated with
      serum liver enzyme, insulin resistance, visceral and subcutaneous fat thickness,
      body fat mass, and percentage body fat. CONCLUSION: The results of this study
      suggest that chronic low-grade systemic inflammation is associated with obesity
      related complications such as nonalcoholic fatty liver disease, insulin
      resistance, and dyslipidemia in young adults.

PMID- 25765162
TI  - Development and validation of correction formulas for self-reported height and
      weight to estimate BMI in adolescents. Results from the KiGGS study.
AB  - OBJECTIVE: The use of reported instead of measured height and weight induces a
      bias in prevalence rates for overweight and obesity. Therefore, correction
      formulas are necessary. METHODS: Self-reported and measured height and weight
      were available from the German Health Interview and Examination Survey for
      Children and Adolescents (KiGGS) baseline study (2003-2006) from 3,468
      adolescents aged 11-17 years. With regression analyses, correction formulas for
      height and weight were developed. Cross-validation was conducted in order to
      validate and compare the formulas. Corrected BMI was calculated, and corrected
      prevalence rates were estimated. Sensitivity, specificity, and predictive values
      for overweight and obesity were calculated. RESULTS: Through the correction
      procedure, the mean differences between reported and measured height and weight
      become remarkably smaller and thus the estimated prevalence rates more accurate.
      The corrected proportions for overweight and obesity are less under-reported,
      while the corrected proportions for underweight are less over-reported.
      Sensitivity for overweight and obesity increased after correction. Specificity
      remained high. CONCLUSION: The validation process showed that the correction
      formulas are an appropriate tool to correct self-reports on an individual level
      in order to estimate corrected prevalence rates of overweight and obesity in
      adolescents for studies which have collected self-reports only.

PMID- 25765163
TI  - Assessment of processes of change for weight management in a UK sample.
AB  - OBJECTIVE: The present study aimed to validate the English version of the
      Processes of Change questionnaire in weight management (P-Weight). METHODS:
      Participants were 1,087 UK adults, including people enrolled in a behavioural
      weight management programme, university students and an opportunistic sample. The
      mean age of the sample was 34.80 (SD = 13.56) years, and 83% were women. BMI
      ranged from 18.51 to 55.36 (mean = 25.92, SD = 6.26) kg/m(2). Participants
      completed both the stages and processes questionnaires in weight management (S
      Weight and P-Weight), and subscales from the EDI-2 and EAT-40. A refined version
      of the P-Weight consisting of 32 items was obtained based on the item analysis.
      RESULTS: The internal structure of the scale fitted a four-factor model, and
      statistically significant correlations with external measures supported the
      convergent validity of the scale. CONCLUSION: The adequate psychometric
      properties of the P-Weight English version suggest that it could be a useful tool
      to tailor weight management interventions.

PMID- 25765165
TI  - Global obesity study on drivers for weight reduction strategies.
AB  - OBJECTIVE: To assess factors determining the reaction of individuals to the
      threats of overweight and obesity and to examine the interdependencies between
      weight-reducing strategies. METHODS: Cross-country survey covering 19 countries
      and 13,155 interviews. Data were analysed using a bivariate probit model that
      allows simultaneously analysing two weight-reducing strategies. RESULTS: Results
      show that weight-reducing strategies chosen are not independent from each other.
      Findings also reveal that different strategies are chosen by different population
      segments. Women are more likely to change their dietary patterns and less likely
      to become physically active after surpassing a weight threshold. In addition, the
      probability of a dietary change in case of overweight differs considerably
      between countries. The study also reveals that attitudes are an important factor
      for the strategy choice. CONCLUSIONS: It is vital for public health policies to
      understand determinants of citizens' engagement in weight reduction strategies
      once a certain threshold is reached. Thus, results can support the design of
      public health campaigns and programmes that aim to change community or national
      health behaviour trends taking into account, e.g., national differences.

PMID- 25765166
TI  - The role of fibrinogen-related proteins in the gastropod immune response.
AB  - Fibrinogen-related proteins or FREPs constitute a large family of molecules,
      defined by the presence of a fibrinogen-related domain (FReD). These molecules
      are found in all animals and are diverse in both form and function. Here, we
      review the current understanding of gastropod FREPs, which are characterized by
      the presence of a fibrinogen domain connected to one or two immunoglobulin
      superfamily domains by way of a short interceding region. We present a historical
      perspective on the discovery of FREPs in gastropods followed by a summary of
      advances made in the nearly two decades of research focused on the
      characterization of FREPs in Biomphalaria glabrata (BgFREPs). Topics covered
      include BgFREP genomic architecture, predicted structure and known functions,
      structural comparisons between BgFREPs, and evidence of somatic diversification.
      Also examined are the expression patterns of BgFREPs during snail development and
      immunological challenges. Recent functional characterization of the role BgFREPs
      play in the defence response against digenean trematodes is also presented, as
      well as new data investigating the nucleotide-level genomic conservation of FREPs
      among Pulmonate gastropods. Finally, we identify areas in need of further
      research. These include confirming and identifying the specific binding targets
      of BgFREPs and elucidating how they later engage snail haemocytes to elicit an
      immunological response, precise mechanisms and importance of BgFREP
      diversification, characterizing the tissue expression patterns of BgFREPs, as
      well as addressing whether gastropod FREPs retain immunological importance in
      alternative snail-trematode associations or more broadly in snail-pathogen
      interactions. 

PMID- 25765164
TI  - Opportunities for intervention strategies for weight management: global actions
      on fluid intake patterns.
AB  - Water is an essential nutrient for all physiological functions and particularly
      important for thermoregulation. About 60% of our body weight is made of water.
      Under standard conditions (18-20  degrees C and moderate activity), water balance
      is regulated within 0.2 % of body weight over a 24-hour period. Water requirement
      varies between individuals and according to environmental conditions. Concerning
      considerations related to obesity, the health impact of fluid intake is commonly
      overlooked. Fluid intake advices are missing in most of food pyramids offered to
      the public, and water requirements and hydration challenges remain often
      neglected. The purpose of this paper is to emphasize and discuss the role of
      water consumption in the context of other important public health measures for
      weight management. Attention will be focused on fluid intake patterns and
      hydration-related questions in the context of global interventions and/or
      physical activity programs settled in weight management protocols.

PMID- 25765167
TI  - Spatial and hydrologic variation of Bacteroidales, adenovirus and enterovirus in
      a semi-arid, wastewater effluent-impacted watershed.
AB  - Bacteroidales and viruses were contemporaneously measured during dry and wet
      weather conditions at a watershed-scale in a semi-arid watershed impacted by a
      mixture of agricultural runoff, municipal wastewater effluent and municipal
      runoff. The results highlight the presence of municipal wastewater effluent as a
      confounding factor for microbial source tracking (MST) studies, and thus data
      were segregated into groups based on whether they were impacted by wastewater
      effluent. In semi-arid environments such as the Calleguas Creek watershed,
      located in southern California, the relative contribution of municipal wastewater
      effluent is dependent on hydrology as storm events lead to conditions where
      agricultural and municipal stormwater dominate receiving waters (rather than
      municipal wastewater, which is the case during dry weather). As such, the
      approach to data segregation was dependent on hydrology/storm conditions. Storm
      events led to significant increases in ruminant- and dog-associated Bacteroidales
      concentrations, indicating that overland transport connects strong non-human
      fecal sources with surface waters. Because the dataset had a large number of non
      detect samples, data handling included the Kaplan-Meir estimator and data were
      presented graphically in a manner that reflects the potential effect of detection
      limits. In surface water samples with virus detections, Escherichia coli
      concentrations were often below (in compliance with) the recreational water
      quality criteria. In fact, sites downstream of direct inputs of municipal
      wastewater effluent exhibited the lowest concentrations of E. coli, but the
      highest concentrations of human-associated Bacteroidales and highest detection
      rates of human viruses. The toolkit, comprised of the four Bacteroidales assays
      and human virus assays used, can be successfully applied to inform watershed
      managers seeking to comply with recreational water quality criteria. However,
      care should be taken when analyzing data to account for the effect of non-detect
      samples, sources with differing microbial viability, and diverging hydrologic
      conditions.

PMID- 25765168
TI  - Remediation of a winery wastewater combining aerobic biological oxidation and
      electrochemical advanced oxidation processes.
AB  - Apart from a high biodegradable fraction consisting of organic acids, sugars and
      alcohols, winery wastewaters exhibit a recalcitrant fraction containing high
      molecular-weight compounds as polyphenols, tannins and lignins. In this context,
      a winery wastewater was firstly subjected to a biological oxidation to mineralize
      the biodegradable fraction and afterwards an electrochemical advanced oxidation
      process (EAOP) was applied in order to mineralize the refractory molecules or
      transform them into simpler ones that can be further biodegraded. The biological
      oxidation led to above 97% removals of dissolved organic carbon (DOC), chemical
      oxygen demand (COD) and 5-day biochemical oxygen demand (BOD5), but was
      inefficient on the degradation of a bioresistant fraction corresponding to 130 mg
      L(-1) of DOC, 380 mg O2 L(-1) of COD and 8.2 mg caffeic acid equivalent L(-1) of
      total dissolved polyphenols. Various EAOPs such as anodic oxidation with
      electrogenerated H2O2 (AO-H2O2), electro-Fenton (EF), UVA photoelectro-Fenton
      (PEF) and solar PEF (SPEF) were then applied to the recalcitrant effluent
      fraction using a 2.2 L lab-scale flow plant containing an electrochemical cell
      equipped with a boron-doped diamond (BDD) anode and a carbon-PTFE air-diffusion
      cathode and coupled to a photoreactor with compound parabolic collectors (CPCs).
      The influence of initial Fe(2+) concentration and current density on the PEF
      process was evaluated. The relative oxidative ability of EAOPs increased in the
      order AO-H2O2 < EF < PEF <= SPEF. The SPEF process using an initial Fe(2+)
      concentration of 35 mg L(-1), current density of 25 mA cm(-2), pH of 2.8 and 25 
      degrees C reached removals of 86% on DOC and 68% on COD after 240 min, regarding
      the biologically treated effluent, along with energy consumptions of 45 kWh (kg
      DOC)(-1) and 5.1 kWh m(-3). After this coupled treatment, color, odor, COD, BOD5,
      NH4(+), NO3(-) and SO4(2-) parameters complied with the legislation targets and,
      in addition, a total dissolved polyphenols content of 0.35 mg caffeic acid
      equivalent L(-1) was found. Respirometry tests revealed low biodegradability
      enhancement along the SPEF process.

PMID- 25765169
TI  - A variable reaction rate model for chlorine decay in drinking water due to the
      reaction with dissolved organic matter.
AB  - A second order kinetic model for simulating chlorine decay in bulk water due to
      the reaction with dissolved organic matter (DOM) was developed. It takes into
      account the decreasing reactivity of dissolved organic matter using a variable
      reaction rate coefficient (VRRC) which decreases with an increasing conversion.
      The concentration of reducing species is surrogated by the maximum chlorine
      demand. Temperature dependency, respectively, is described by the Arrhenius
      relationship. The accuracy and adequacy of the proposed model to describe
      chlorine decay in bulk water were evaluated and shown for very different waters
      and different conditions such as water mixing or rechlorination by applying
      statistical tests. It is thus very well suited for application in water quality
      modeling for distribution systems.

PMID- 25765170
TI  - Delayed increase in male suicide rates in tsunami disaster-stricken areas
      following the great east japan earthquake: a three-year follow-up study in Miyagi
      Prefecture.
AB  - Devastating natural disasters and their aftermath are known to cause
      psychological distress. However, little information is available regarding
      suicide rates following tsunami disasters that destroy regional social services
      and networks. The aim of the present study was to determine whether the tsunami
      disaster following the Great East Japan Earthquake in March 2011 has influenced
      suicide rates. The study period was from March 2009 to February 2014. Tsunami
      disaster-stricken areas were defined as the 16 municipalities facing the Pacific
      Ocean in Miyagi Prefecture. Inland areas were defined as other municipalities in
      Miyagi that were damaged by the earthquake. Suicide rates in the tsunami disaster
      stricken areas were compared to national averages, using a time-series analysis
      and the Poisson distribution test. In tsunami disaster-stricken areas, male
      suicide rates were significantly lower than the national average during the
      initial post-disaster period and began to increase after two years. Likewise,
      male suicide rates in the inland areas decreased for seven months, and then
      increased to exceed the national average. In contrast, female post-disaster
      suicide rates did not change in both areas compared to the national average.
      Importantly, the male suicide rates in the inland areas started to increase
      earlier compared to the tsunami-stricken areas, which may reflect the relative
      deficiency of mental healthcare services in the inland areas. Considering the
      present status that many survivors from the tsunami disaster still live in
      temporary housing and face various challenges to rebuild their lives, we should
      continue intensive, long-term mental healthcare services in the tsunami-stricken
      areas. 

PMID- 25765171
TI  - Cytological scoring and prognosis of poorly differentiated endometrioid
      adenocarcinoma.
AB  - OBJECTIVE: Histopathological variation has been demonstrated in grade 3
      endometrioid adenocarcinomas. We attempted to evaluate the clinicopathological
      features of grade 3 tumors by endometrial cytological features using a scoring
      system. STUDY DESIGN: Twenty-one endometrial cytological samples were evaluated
      using 5 cytological features: rates of cluster formation in tumor cells; nuclear
      pleomorphism; nuclear dimension; size of nucleoli, and chromatin structure and
      distribution. The relationships between cytological scores and
      clinicopathological factors or prognosis were investigated. RESULTS: The median
      cytological score was 6 (range 4-14); therefore, samples with scores of 4-5 were
      defined as having low scores, while those with scores of 6-14 were defined as
      high scores. The accuracy of the cytological diagnosis for grade 3 tumors in the
      high score group (8/10 patients, 80.0%) was significantly higher than that of the
      low score group (2/11 patients, 18.2%; p=0.009). Significant relationships
      between cytological scores and lymph node metastases or positive peritoneal
      cytology were observed (p=0.03 and 0.035, respectively). The overall survival
      rate was significantly worse in the high score group (30.0%) than the low score
      group (88.9%; p=0.02). CONCLUSIONS: Grade 3 endometrioid adenocarcinomas varied
      in cytological features; according to the scoring system used, high scores were
      associated with worse clinicopathological factors and poorer prognosis than low
      scores.

PMID- 25765172
TI  - Dendrimerlike mesoporous silica nanoparticles as pH-responsive nanocontainers for
      targeted drug delivery and bioimaging.
AB  - In this work, we employed dendrimerlike mesoporous silica nanoparticles with
      hierarchical pores (HPSNs) to fabricate drug delivery system bioimaging and
      targeted tumor therapy in vivo. N,N-phenylenebis(salicylideneimine)dicarboxylic
      acid (Salphdc) was used both as the gatekeeper of HPSNs via pH-responsive
      coordination bonds between -COOH of Salphdc and In(3+) ions and as a fluorescence
      imaging agent. Folic acid was then conjugated to Salphdc as the targeting unit.
      The results revealed that the system could deliver model drug DOX to the tumor
      site with high efficiency and then cause cell apoptosis and tumor growth
      inhibition. Moreover, the conjugated Salphdc was proved to be a promising
      fluorescence probe for tracing distribution of the system in vivo. The study
      affords a potential nanoconainer for cancer therapy and biological imaging. 

PMID- 25765173
TI  - Even the smallest mammalian brain has yet to reveal its secrets.

PMID- 25765174
TI  - Effects of stoichiometric doping in superconducting Bi-O-S compounds.
AB  - Newly discovered Bi-O-S compounds remain an enigma in attempts to understand
      their electronic properties. A recent study of Bi4O4S3 has shown it to be a
      mixture of two phases, Bi2OS2 and Bi3O2S3, the latter being superconducting
      (Phelan et al 2013 J. Am. Chem. Soc. 135 5372-4). Using density functional
      theory, we explore the electronic structure of both the phases and the effect of
      the introduction of extra BiS2 bilayers. Our results demonstrate that the S2
      layers dope the bismuth-sulphur bands and this causes metallisation. The bands at
      the Fermi level are of clear two-dimensional character. One band manifold is
      confined to the two adjacent, square-lattice bismuth-sulphur planes, a second
      manifold is confined to the square lattice of sulphur dimers. We show that the
      introduction of extra BiS2 bilayers does not influence the electronic structure.
      Finally, we also show that spin-orbit coupling does not have any significant
      effect on the states close to the Fermi level at the energy scale considered. 

PMID- 25765175
TI  - The role of SPARC expression in pancreatic cancer progression and patient
      survival.
AB  - BACKGROUND: Secreted protein acidic and rich in cysteine (SPARC) is a
      matricellular glycoprotein that has been implicated in tumor-stroma interactions
      in pancreatic cancer. Here we evaluated the expression of SPARC during the
      progression of pancreatic cancer and its correlation with survival following
      curative intent surgery. METHODS: The expression profile of SPARC was
      investigated in normal pancreas, invasive adenocarcinoma, and lymph node
      metastasis by immunohistochemistry. Kaplan-Meier and multivariate Cox regression
      were used to assess for mortality risk. RESULTS: None (0%) of 10 normal
      pancreata, 68 (77%) of 88 primary tumors, and 28 (67%) of 42 lymph node
      metastases were labeled with the SPARC antibody used in this study. SPARC was
      expressed exclusively in stromal cells. The survival of patients with high
      stromal SPARC expression was significantly worse than that of the patients with
      low stromal SPARC expression (11.5 vs 25.3 months; p = 0.020). Multivariate
      analysis showed that stromal SPARC expression (hazard ratio (HR) 2.12; p =
      0.012), tumor location (body/tail) (HR 2.95; p = 0.003), and adjuvant
      chemotherapy (HR 0.55; p = 0.018) were significant independent risk factors.
      CONCLUSION: This study describes the pattern of SPARC expression in pancreatic
      neoplastic progression and supports the role of stromal SPARC expression as a
      prognostic factor and target for directed therapy.

PMID- 25765176
TI  - Characterization and survival of environmental Escherichia coli O26 isolates in
      ground beef and environmental samples.
AB  - In addition to Escherichia coli O157:H7, shiga toxin-producing E. coli (STEC) O26
      was added to the zero-tolerance adulterant list together with other 5 non-O157
      STEC serogroups in 2012. Four farm O26 isolates were used in this study; they
      were obtained from a on-farm survey study conducted in Alabama. The presence of 3
      major pathogenic genes (stx1, stx2, and eaeA) was determined through multiplex
      polymerase chain reaction (PCR). Two major pathogenic gene profiles were
      observed: 3 of the farm isolates contain only the eaeA gene whereas 1 farm
      isolate has both the eaeA and the stx1 genes. No significant difference was seen
      among the 4 farm isolates in the antibiotic resistance tests. To test their
      survival in ground beef and environmental samples, 2 inoculums were prepared and
      inoculated at various concentrations into samples of ground beef, bovine feces,
      bedding materials, and trough water. One inoculum was made of 3 farm isolates
      containing only the eaeA gene and another inoculum contained the isolate with
      both the eaeA and stx1 genes. Inoculated beef samples were stored at 4  degrees C
      for 10 d and the inoculated environmental samples were stored at ambient
      temperature for 30 d. Results showed that virulence gene profiles do not have an
      impact on O26's ability to survive in ground beef and in environment (P > 0.05).
      The inoculation levels, sample types as well as the storage times are the major
      factors that impact O26 survival (P < 0.05). 

PMID- 25765177
TI  - Mechanism study of alachlor biodegradation by Paecilomyces marquandii with
      proteomic and metabolomic methods.
AB  - Alachlor is an herbicide that is widely used worldwide to protect plant crops
      against broadleaf weeds and annual grasses. However, due to its endocrine
      disrupting activity, its application had been banned in the European Union. As
      described in our earlier work, Paecilomyces marquandii is a microscopic fungus
      capable of alachlor removal by N-acetyl oxidation. Our current work uses
      proteomics and metabolomics to gain a better understanding of alachlor
      biodegradation by the microscopic fungus P. marquandii. The data revealed that
      the addition of alachlor reduced the culture growth and glucose consumption
      rates. Moreover, the rates of glycolysis and the tricarboxylic acids (TCA) cycle
      increased during the initial stage of growth, and there was a shift toward the
      formation of supplementary materials (UDP-glucose/galactose) and reactive oxygen
      species (ROS) scavengers (ascorbate). Proteomic analysis revealed that the
      presence of xenobiotics resulted in a strong upregulation of enzymes related to
      energy, sugar metabolism and ROS production. However, the unique overexpression
      of cyanide hydratase in alachlor-containing cultures may implicate this enzyme as
      the key protein involved in the alachlor biodegradation pathway. The
      characterization of P. marquandii-mediated alachlor removal in terms of cell
      structure and function provides a deeper insight into the strategies of
      microorganisms toward xenobiotic biodegradation. 

PMID- 25765178
TI  - Configuring the patient as clinical research subject in the UK national health
      service.
AB  - This paper examines a central image in UK academic clinical research - the
      patient as altruistic research subject - by means of an interpretive review of
      social science, bioethical and bioscience research and development policy
      literatures. The review examines this image as it is indicted in discussions
      about the nature of clinical science; is consolidated in the ethical regulation
      of this science; and is articulated in recent bioscience research and development
      government initiatives. Drawing on Strathern's notion of the virtual (public
      sector) subject, the review identifies the anticipation of NHS patients as
      alternatively 'available' or 'entitled' to the expanding translational medicine
      industry. 

PMID- 25765179
TI  - Somatostatin Receptors 2A and 5 Are Expressed in Merkel Cell Carcinoma with No
      Association with Disease Severity.
AB  - BACKGROUND/AIMS: Merkel cell carcinoma (MCC) is a rare high-grade neuroendocrine
      tumour of the skin. It has been speculated that MCCs express somatostatin
      receptors (SSTRs), but this has never been assessed in a large series of MCCs.
      The main aim of this study was to assess the expression of SSTR2A and SSTR5 in
      MCC tumours. The secondary aims were to assess whether expression of SSTR was
      associated with the Ki67 proliferative index, Merkel cell polyomavirus (MCPyV)
      status, clinical characteristics and outcome. METHODS: Clinical data and tumours
      were collected from an ongoing cohort of French patients with MCC.
      Immunohistochemistry was performed with anti-SSTR2A and anti-SSTR5 monoclonal
      antibodies, and tumours were classified into 3 groups: 'no expression', 'low
      expression' and 'moderate expression' using an SSTR staining score. RESULTS: SSTR
      expression was assessed for 105 MCC tissue samples from 98 patients, and clinical
      characteristics were available for 87 of them. SSTR expression was consistent
      between the primary skin tumour and the corresponding metastases for SSTR2A and
      SSTR5 in 3/7 and 6/7 cases, respectively. SSTR2A and SSTR5 were expressed in 58
      cases (59.2%) and in 44 cases (44.9%), respectively. Overall, at least one SSTR
      was expressed in 75 tumours (76.5%). SSTR expression was not associated with
      clinical characteristics, Ki67 proliferative index, recurrence-free survival or
      MCC-specific survival. Expression of SSTR2A was associated with MCPyV status in
      MCC tumours but not SSTR5. CONCLUSION: SSTRs were expressed in a high proportion
      of MCCs, although expression was heterogeneous between tumours and was not
      associated with disease severity.

PMID- 25765180
TI  - Sudden sensorineural hearing loss associated with tension-type headache: a
      population-based study.
AB  - OBJECTIVES: This study explored the relationship between sudden sensorineural
      hearing loss (SSNHL) and prior tension-type headache (TTH) in a large nationwide
      population-based data set in Taiwan. METHODS: In this case-controlled study in
      Taiwan, participants with SSNHL (n = 4,683) were identified, and controls (n =
      18,732) were randomly selected from the National Health Insurance database. Cases
      of TTH were identified by having been diagnosed as TTH prior to the index date of
      SSNHL diagnosis. A conditional logistic regression model was used to estimate the
      adjusted odds ratio (OR) and 95% confidence intervals (CI) for the association of
      sudden deafness with TTH among the sampled patients. RESULTS: Among the 23,415
      patients, 2.5% (600/23,415) had TTH diagnoses prior to the index date; TTH was
      diagnosed in 4.5% (209/4,683) of the SSNHL group and 2.1% (391/18,732) of the
      control group. After adjusting for sociodemographic characteristics and comorbid
      medical disorders, we found that patients with SSNHL were more likely to have had
      a previous TTH than controls (OR, 1.86; 95% CI, 1.54-2.24; p < 0.01). CONCLUSION:
      Both male and female patients with SSNHL had a higher proportion of prior TTH
      than controls without SSNHL.

PMID- 25765181
TI  - Identification of Candidate Gene Variants in Korean MODY Families by Whole-Exome
      Sequencing.
AB  - AIMS: To date, 13 genes causing maturity-onset diabetes of the young (MODY) have
      been identified. However, there is a big discrepancy in the genetic locus between
      Asian and Caucasian patients with MODY. Thus, we conducted whole-exome sequencing
      in Korean MODY families to identify causative gene variants. METHODS: Six MODY
      probands and their family members were included. Variants in the dbSNP135 and
      TIARA databases for Koreans and the variants with minor allele frequencies >0.5%
      of the 1000 Genomes database were excluded. We selected only the functional
      variants (gain of stop codon, frameshifts and nonsynonymous single-nucleotide
      variants) and conducted a case-control comparison in the family members. The
      selected variants were scanned for the previously introduced gene set implicated
      in glucose metabolism. RESULTS: Three variants c.620C>T:p.Thr207Ile in PTPRD,
      c.559C>G:p.Gln187Glu in SYT9, and c.1526T>G:p.Val509Gly in WFS1 were respectively
      identified in 3 families. We could not find any disease-causative alleles of
      known MODY 1-13 genes. Based on the predictive program, Thr207Ile in PTPRD was
      considered pathogenic. CONCLUSIONS: Whole-exome sequencing is a valuable method
      for the genetic diagnosis of MODY. Further evaluation is necessary about the role
      of PTPRD, SYT9 and WFS1 in normal insulin release from pancreatic beta cells.

PMID- 25765182
TI  - Heterogeneous tumor stromal microenvironments of oral squamous cell carcinoma
      cells in tongue and nodal metastatic lesions in a xenograft mouse model.
AB  - BACKGROUND: Oral squamous cell carcinoma exhibits a poor prognosis, caused by
      aggressive progression and early-stage metastasis to cervical lymph nodes. Here,
      we developed a xenograft mouse model to explore the heterogeneity of the tumor
      microenvironment that may govern local invasion and nodal metastasis of tumor
      cells. METHODS: We transplanted five oral carcinoma cell lines into the tongues
      of nude mice and determined tongue tumor growth and micrometastatic dissemination
      by serially sectioning the tongue and lymph node lesions in combination with
      immunohistochemistry and computer-assisted image analysis. Our morphometric
      analysis enabled a quantitative assessment of blood and lymphatic endothelial
      densities in the intratumoral and host stromal regions. RESULTS: All cell lines
      tested were tumorigenic in mouse tongue. The metastatic lesion-derived carcinoma
      cell lines (OSC19, OSC20, and HSC2) yielded a 100% nodal metastasis rate, whereas
      the primary tumor-derived cell lines (KOSC2 and HO-1-u-1) showed <40% metastatic
      potential. Immunohistochemistry showed that the individual cell lines gave rise
      to heterogeneous tumor architecture and phenotypes and that their micrometastatic
      lesions assimilated the immunophenotypic properties of the corresponding tongue
      tumors. Notably, OSC19 and OSC20 cells shared similar aggressive tumorigenicity
      in both the tongue and lymph node environments but displayed markedly diverse
      immunophenotypes and gene expression profiles. CONCLUSIONS: Our model facilitated
      comparing the tumor microenvironments in tongue and lymph node lesions. The
      results support that tumorigenicity and tumor architecture in the host tongue
      environment depend on the origin and properties of the carcinoma cell lines and
      that metastatic progression may take place through heterogeneous tumor-host
      interactions.

PMID- 25765183
TI  - Is Chemoradiotherapy Beneficial for Stage IV Rectal Cancer?
AB  - PURPOSE: The aim of this study was to investigate the oncologic impact of
      preoperative or postoperative chemoradiotherapy on stage IV rectal cancer.
      METHODS: A total of 140 consecutive patients with locally advanced mid-to-lower
      rectal cancer and resectable stage IV disease were prospectively enrolled. In
      total, 69 patients received chemoradiotherapy (26 preoperatively and 43
      postoperatively); in contrast, 71 did not. Survival curves were constructed using
      the Kaplan-Meier method, and a multivariate analysis was performed to identify
      independent prognostic factors. RESULTS: According to the multivariate analysis,
      radiation therapy was not an independent factor associated with either survival
      or recurrence. The overall survival curves revealed that patients who underwent
      radiotherapy tended to have a better survival compared with patients who did not
      undergo radiotherapy; however, this trend was not statistically significant (p =
      0.057). The disease-free, local recurrence-free, and distant metastasis-free
      survival curves did not differ significantly between the two groups. The local
      recurrence-free survival rates for patients who underwent preoperative
      radiotherapy were significantly higher than those for patients who underwent
      postoperative radiotherapy (p = 0.042). CONCLUSION: Preoperative radiotherapy,
      rather than postoperative radiotherapy, may improve local control of stage IV
      rectal cancer. However, chemoradiotherapy did not improve the survival of
      patients with stage IV rectal cancer in this study.

PMID- 25765184
TI  - Structural insights into the inhibition of cellobiohydrolase Cel7A by xylo
      oligosaccharides.
AB  - The filamentous fungus Hypocrea jecorina (anamorph of Trichoderma reesei) is the
      predominant source of enzymes for industrial saccharification of lignocellulose
      biomass. The major enzyme, cellobiohydrolase Cel7A, constitutes nearly half of
      the total protein in the secretome. The performance of such enzymes is
      susceptible to inhibition by compounds liberated by physico-chemical pre
      treatment if the biomass is kept unwashed. Xylan and xylo-oligosaccharides (XOS)
      have been proposed to play a key role in inhibition of cellobiohydrolases of
      glycoside hydrolase family 7. To elucidate the mechanism behind this inhibition
      at a molecular level, we used X-ray crystallography to determine structures of H.
      jecorina Cel7A in complex with XOS. Structures with xylotriose, xylotetraose and
      xylopentaose revealed a predominant binding mode at the entrance of the substrate
      binding tunnel of the enzyme, in which each xylose residue is shifted ~ 2.4 A
      towards the catalytic center compared with binding of cello-oligosaccharides.
      Furthermore, partial occupancy of two consecutive xylose residues at subsites -2
      and -1 suggests an alternative binding mode for XOS in the vicinity of the
      catalytic center. Interestingly, the -1 xylosyl unit exhibits an open aldehyde
      conformation in one of the structures and a ring-closed pyranoside in another
      complex. Complementary inhibition studies with p-nitrophenyl lactoside as
      substrate indicate mixed inhibition rather than pure competitive inhibition.
      DATABASE: The atomic coordinates and structure factors are available in the
      Protein Data Bank under accession number 4D5I (H. jecorina Cel7A E212Q variant,
      complex with xylotriose), 4D5J (H. jecorina Cel7A E217Q variant, complex with
      xylotriose), 4D5O (H. jecorina Cel7A E212Q variant, complex with xylopentaose),
      4D5P (H. jecorina Cel7A E217Q variant, complex with xylopentaose), 4D5Q (wild
      type H. jecorina Cel7A, complex with xylopentaose) and 4D5V (H. jecorina Cel7A
      E217Q variant, complex with xylotetraose).

PMID- 25765186
TI  - [Rational estimation of drug dosage through pharmacometric modeling: The case of
      a long-acting depot antipsychotic].
AB  - Drug manufacturer seeking authorization to bring a newly medicinal compound to
      the market (Market Authorization Application) have to undertake various studies,
      each of them providing a specific report. It is however essential to know how to
      pool results in order to understand the behavior of the drug in all the
      situations likely to be encountered in clinical practice. The exploitation of
      these data is now carried out through pharmacometric analyzes which aim at
      quantifying the exposure and the response of a drug over time. These methods
      (named "population approach") are based on non-linear mixed effects model and
      therefore, on the identification of a mathematical model. A first step is to
      model the variations in concentrations over time by integrating the physio
      pathological characteristics of the patients. At this stage, the Bayesian
      analysis is essential to identify and select the factors of interindividual
      variability. This pharmacokinetic (PK) modeling allows us to obtain the
      prescribed dose for each patient, but also their exposure. The second step
      consists in defining the relationship between exposure and effect:
      pharmacodynamic (PD) modeling. In psychiatry, the response can be the receptors'
      occupancy rate or the evolution of a clinical score (BPRS, PANSS...) over time.
      The final PK-PD model defines the target exposure, that is to say, the
      concentration values required to achieve maximum effect on the score studied
      without risking over-exposure. Ultimately, a Monte Carlo simulation will be
      conducted which will test the expected response for different doses and will
      facilitate a rational choice in dosage. Assessing the process behind the
      transition from an oral to a long-acting injectable form of an active ingredient
      such as aripiprazole can be done by following the same protocol. A 10- to 30-mg
      per day therapeutic range has thus been identified. The model incorporates all
      the identified factors of variability of aripiprazole (drug interactions and
      genetic polymorphism of the P450 2D6 cytochrome) and showed that with an
      injectable sustained release form, a monthly dose of 400mg would allow 90% of
      patients to gain exposure in the therapeutic range. In case of a drug inhibition
      and/or of a slow metabolizing profile, dosage adjustment is necessary. 

PMID- 25765185
TI  - Sequence and analysis of a whole genome from Kuwaiti population subgroup of
      Persian ancestry.
AB  - BACKGROUND: The 1000 Genome project paved the way for sequencing diverse human
      populations. New genome projects are being established to sequence
      underrepresented populations helping in understanding human genetic diversity.
      The Kuwait Genome Project an initiative to sequence individual genomes from the
      three subgroups of Kuwaiti population namely, Saudi Arabian tribe; "tent
      dwelling" Bedouin; and Persian, attributing their ancestry to different regions
      in Arabian Peninsula and to modern-day Iran (West Asia). These subgroups were in
      line with settlement history and are confirmed by genetic studies. In this work,
      we report whole genome sequence of a Kuwaiti native from Persian subgroup at >37X
      coverage. RESULTS: We document 3,573,824 SNPs, 404,090 insertions/deletions, and
      11,138 structural variations. Out of the reported SNPs and indels, 85,939 are
      novel. We identify 295 'loss-of-function' and 2,314 'deleterious' coding
      variants, some of which carry homozygous genotypes in the sequenced genome; the
      associated phenotypes include pharmacogenomic traits such as greater triglyceride
      lowering ability with fenofibrate treatment, and requirement of high warfarin
      dosage to elicit anticoagulation response. 6,328 non-coding SNPs associate with
      811 phenotype traits: in congruence with medical history of the participant for
      Type 2 diabetes and beta-Thalassemia, and of participant's family for migraine,
      72 (of 159 known) Type 2 diabetes, 3 (of 4) beta-Thalassemia, and 76 (of 169)
      migraine variants are seen in the genome. Intergenome comparisons based on shared
      disease-causing variants, positions the sequenced genome between Asian and
      European genomes in congruence with geographical location of the region. On
      comparison, bead arrays perform better than sequencing platforms in correctly
      calling genotypes in low-coverage sequenced genome regions however in the event
      of novel SNP or indel near genotype calling position can lead to false calls
      using bead arrays. CONCLUSIONS: We report, for the first time, reference genome
      resource for the population of Persian ancestry. The resource provides a starting
      point for designing large-scale genetic studies in Peninsula including Kuwait,
      and Persian population. Such efforts on populations under-represented in global
      genome variation surveys help augment current knowledge on human genome
      diversity.

PMID- 25765187
TI  - Evaluating the relationship between plasma and skin carotenoids and reported
      dietary intake in elementary school children to assess fruit and vegetable
      intake.
AB  - Accurate assessment of dietary intake of children can be challenging due to the
      limited reliability of current dietary assessment methods. Plasma carotenoid
      concentration has been used to assess fruit and vegetable intake, but this
      testing is rarely conducted in school settings in children. Resonance Raman
      spectroscopy (RRS) is emerging as a useful method to objectively assess fruit and
      vegetable intake. This methodology has been validated in adults, but limited work
      has been done in children, particularly in the school setting. The purpose of
      this research is to further validate the RRS methodology in children. Children (9
      12 year) participating in a school-based intervention were recruited. Plasma
      carotenoids were quantified using HPLC, skin carotenoid status was measured using
      RRS, and dietary intake of carotenoids was measured with the Block Food Frequency
      Questionnaire Ages 8-17. Total plasma carotenoid concentrations and skin
      carotenoid intensities were strongly correlated (r=0.62, p<0.001, n=38). Reported
      total carotenoid intake correlated with skin carotenoids (r=0.40, p<0.0001,
      n=128). Skin carotenoid status as measured by RRS can be a strong predictor of
      plasma carotenoid status and dietary intake of carotenoids in children. RRS may
      be used as a valid, non-invasive, and useful method to assess fruit and vegetable
      intakes in this population.

PMID- 25765188
TI  - Comparative analysis among the small RNA populations of source, sink and
      conductive tissues in two different plant-virus pathosystems.
AB  - BACKGROUND: In plants, RNA silencing plays a fundamental role as defence
      mechanism against viruses. During last years deep-sequencing technology has
      allowed to analyze the sRNA profile of a large variety of virus-infected tissues.
      Nevertheless, the majority of these studies have been restricted to a unique
      tissue and no comparative analysis between phloem and source/sink tissues has
      been conducted. In the present work, we compared the sRNA populations of source,
      sink and conductive (phloem) tissues in two different plant virus pathosystems.
      We chose two cucurbit species infected with two viruses very different in genome
      organization and replication strategy; Melon necrotic spot virus (MNSV) and
      Prunus necrotic ringspot virus (PNRSV). RESULTS: Our findings showed, in both
      systems, an increase of the 21-nt total sRNAs together with a decrease of those
      with a size of 24-nt in all the infected tissues, except for the phloem where the
      ratio of 21/24-nt sRNA species remained constant. Comparing the vsRNAs, both
      PNRSV- and MNSV-infected plants share the same vsRNA size distribution in all the
      analyzed tissues. Similar accumulation levels of sense and antisense vsRNAs were
      observed in both systems except for roots that showed a prevalence of (+) vsRNAs
      in both pathosystems. Additionally, the presence of overrepresented discrete
      sites along the viral genome, hot spots, were identified and validated by stem
      loop RT-PCR. Despite that in PNRSV-infected plants the presence of vsRNAs was
      scarce both viruses modulated the host sRNA profile. CONCLUSIONS: We compare for
      the first time the sRNA profile of four different tissues, including source, sink
      and conductive (phloem) tissues, in two plant-virus pathosystems. Our results
      indicate that antiviral silencing machinery in melon and cucumber acts mainly
      through DCL4. Upon infection, the total sRNA pattern in phloem remains unchanged
      in contrast to the rest of the analyzed tissues indicating a certain tissue
      tropism to this polulation. Independently of the accumulation level of the vsRNAs
      both viruses were able to modulate the host sRNA pattern.

PMID- 25765190
TI  - Number and localization of the implants for the fixed prosthetic reconstructions:
      on the strain in the anterior maxillary region.
AB  - Resorption following tooth loss and poor bone quality affect the success of
      implants in the anterior maxilla. Inappropriate planning can cause implant loss
      and aesthetics problems that are difficult to resolve. There is a limited
      literature on the optimum number and location of implants in anterior maxilla for
      fabricating fixed prosthesis in biomechanical terms. This study investigated the
      effect of dental implant localizations in anterior maxilla on the strain values
      around implants using a three dimensional finite elements analysis method.
      Obtained strain values were compared to the data in Frost's mechanostat theory.
      The entire totally edentulous maxilla was modeled using computer tomography
      images and five models were prepared representing different implant
      localizations. The distribution of implants in the models was as follows: two
      canines in the first model, two canines and one central incisor in the second
      model, two canines and central incisor in the third model, two canines and one
      lateral incisor in the fourth model and two canines and two lateral incisors in
      the fifth model. Anatomic abutments with a gingival height of 2 mm and angle of
      15 degrees  were used as the abutments to fabricate one piece cemented metal
      fused to porcelain restoration. A chewing strength of 100 N was applied to the
      cingulum of all crowns at a 45 degrees  angle. Maximum strain values in all
      models were measured in cortical bone in implant necks. The highest strain value
      was measured in the first model at the cortical bone area (3037 microstrain).
      Except the first model, all models showed micro strain values within 1000-3000
      microstrain. The fifth model was the least risky method in biomechanical terms.
      The results of this study should be compared with different clinical scenarios
      (for example different implant designs and sizes). Due to the limitations of
      three-dimensional finite elements analysis studies, the findings of the study
      need to be supported by clinical studies. 

PMID- 25765189
TI  - Numerical and experimental investigation of the structural behavior of a carbon
      fiber reinforced ankle-foot orthosis.
AB  - Ankle-foot orthoses (AFOs) are designed to enhance the gait function of
      individuals with motor impairments. Recent AFOs are often made of laminated
      composites due to their high stiffness and low density. Since the performance of
      AFO is primarily influenced by their structural stiffness, the investigation of
      the mechanical response is very important for the design. The aim of this paper
      is to present a three dimensional multi-scale structural analysis methodology to
      speed up the design process of AFO. The multi-scale modeling procedure was
      applied such that the intrinsic micro-structure of the fiber reinforced laminates
      could be taken into account. In particular, representative volume elements were
      used on the micro-scale, where fiber and matrix were treated separately, and on
      the textile scale of the woven structure. For the validation of this methodology,
      experimental data were generated using digital image correlation (DIC)
      measurements. Finally, the structural behavior of the whole AFO was predicted
      numerically for a specific loading scenario and compared with experimental
      results. It was shown that the proposed numerical multi-scale scheme is well
      suited for the prediction of the structural behavior of AFOs, validated by the
      comparison of local strain fields as well as the global force-displacement
      curves. 

PMID- 25765191
TI  - The Use of Antidepressant Medication before and after the Diagnosis of
      Amyotrophic Lateral Sclerosis: A Population-Based Cohort Study.
AB  - BACKGROUND: The prevalent use of antidepressants (ATDs) in patients with
      Amyotrophic Lateral Sclerosis (ALS) varies across cross-sectional and clinic
      based published studies. This population-based cohort study assesses the real
      world prevalence of the use of ATDs, its trajectory and the association of
      incident use with clinical characteristics. METHODS: All patients with incident
      ALS in the Friuli Venezia Giulia region, Italy, from 2002 to 2009, were
      identified through multiple sources including health databases. Diagnosis was
      validated through clinical documentation review. ATDs prescriptions from 2000 to
      2011 were obtained from regional database. The trajectory was estimated through
      generalized estimating equations for repeated measures logistic regression and
      the Hazard ratio (HR) of initiating ATDs through multivariate proportional hazard
      Cox regression. RESULTS: In this cohort of 261 ALS cases, age-, sex-adjusted
      prevalence of the use of ATDs was 37.3%, higher than in general population. The
      trajectory increased by 16% in 1-year period across diagnosis. Age <=67 years at
      diagnosis (HR 1.28, 95% CI 0.84-1.95) and bulbar onset (1.43, 95% CI 0.90-2.26)
      were positively associated with initiating ATDs after diagnosis. CONCLUSIONS:
      More than one-third of patients used ATDs. Depression may occur more frequently
      than previously reported. Depression may precede motor alterations and be related
      to both ALS diagnosis and progression.

PMID- 25765192
TI  - The Allee effect and elimination of neglected tropical diseases: a mathematical
      modelling study.
AB  - Elimination and control programmes for neglected tropical diseases (NTDs) are
      underway around the world, yet they are generally informed by epidemiological
      modelling only to a rudimentary degree. Chief among the modelling-derived
      predictors of disease emergence or controllability is the basic reproduction
      number R0. The ecological systems of several of the NTDs include density
      dependent processes--which alter the rate of e.g. parasite establishment or
      fecundity--that complicate the calculation of R0. Here we show how the forms of
      the density-dependent functions for a model of the NTD lymphatic filariasis
      affect the effective reproduction number Reff. We construct infection
      transmission models containing various density-dependent functions and show how
      they alter the shape of the Reff profile, affecting two important epidemiological
      outcome variables that relate to elimination and control programmes: the parasite
      transmission breakpoint (or extinction threshold) and the reproduction fitness,
      as measured by Reff. The current drive to control, eliminate or eradicate several
      parasitic infections would be substantially aided by the existence of ecological
      Allee effects. For these control programmes, the findings of this paper are
      encouraging, since a single positive density dependency (DD) can introduce a
      reasonable chance of achieving elimination; however, there are diminishing
      returns to additional positive DDs.

PMID- 25765193
TI  - Mathematical modelling of leprosy and its control.
AB  - Leprosy or Hansen's disease is an infectious disease caused by the bacterium
      Mycobacterium leprae. The annual number of new leprosy cases registered worldwide
      has remained stable over the past years at over 200,000. Early case finding and
      multidrug therapy have not been able interrupt transmission completely.
      Elimination requires innovation in control and sustained commitment. Mathematical
      models can be used to predict the course of leprosy incidence and the effect of
      intervention strategies. Two compartmental models and one individual-based model
      have been described in the literature. Both compartmental models investigate the
      course of leprosy in populations and the long-term impact of control strategies.
      The individual-based model focusses on transmission within households and the
      impact of case finding among contacts of new leprosy patients. Major improvement
      of these models should result from a better understanding of individual
      differences in exposure to infection and developing leprosy after exposure. Most
      relevant are contact heterogeneity, heterogeneity in susceptibility and spatial
      heterogeneity. Furthermore, the existing models have only been applied to a
      limited number of countries. Parameterization of the models for other areas, in
      particular those with high incidence, is essential to support current initiatives
      for the global elimination of leprosy. Many challenges remain in understanding
      and dealing with leprosy. The support of mathematical models for understanding
      leprosy epidemiology and supporting policy decision making remains vital. 

PMID- 25765194
TI  - Mathematical models of human african trypanosomiasis epidemiology.
AB  - Human African trypanosomiasis (HAT), commonly called sleeping sickness, is caused
      by Trypanosoma spp. and transmitted by tsetse flies (Glossina spp.). HAT is
      usually fatal if untreated and transmission occurs in foci across sub-Saharan
      Africa. Mathematical modelling of HAT began in the 1980s with extensions of the
      Ross-Macdonald malaria model and has since consisted, with a few exceptions, of
      similar deterministic compartmental models. These models have captured the main
      features of HAT epidemiology and provided insight on the effectiveness of the two
      main control interventions (treatment of humans and tsetse fly control) in
      eliminating transmission. However, most existing models have overestimated
      prevalence of infection and ignored transient dynamics. There is a need for
      properly validated models, evolving with improved data collection, that can
      provide quantitative predictions to help guide control and elimination strategies
      for HAT. 

PMID- 25765195
TI  - Ecology, evolution and control of Chagas disease: a century of neglected
      modelling and a promising future.
AB  - More than 100 years after its formal description, Chagas disease remains a major
      public health concern in Latin America with a yearly burden of 430,000 Disability
      Adjusted Life Years (DALYs). The aetiological agent, a protozoan named
      Trypanosoma cruzi, is mainly transmitted to mammalian hosts by triatomine
      vectors. Multiple species of mammals and triatomines can harbour and transmit the
      parasite, and the feeding range of triatomine species typically includes many
      noncompetent hosts. Furthermore, the transmission of the pathogen can occur via
      several routes including the typical vector's faeces, but also oral, congenital
      and blood transfusion routes. These ecological and epidemiological complexities
      of the disease have hindered many control initiatives. In such a context,
      mathematical models provide invaluable tools to explore and understand the
      dynamics of T. cruzi transmission, and to design, optimize and monitor the
      efficacy of control interventions. We intend here to provide the first review of
      the mathematical models of Chagas disease, focussing on how they have contributed
      to our understanding of (1) the population dynamics and control of triatomine
      vectors, and (2) the epidemiology of T. cruzi infections. We also aim at
      suggesting promising lines of modelling that could further improve our
      understanding of the ecology, evolution, and control of the disease. 

PMID- 25765196
TI  - Mathematical inference on helminth egg counts in stool and its applications in
      mass drug administration programmes to control soil-transmitted helminthiasis in
      public health.
AB  - In the present study, we present a hierarchical model based on faecal egg counts
      (FECs; expressed in eggs per 1g of stool) in which we first describe the
      variation in FECs between individuals in a particular population, followed by
      describing the variance due to counting eggs under a microscope separately for
      each stool sample. From this general framework, we discuss how to calculate a
      sample size for assessing a population mean FEC and the impact of an
      intervention, measured as reduction in FECs, for any scenario of soil-transmitted
      helminth (STH) epidemiology (the intensity and aggregation of FECs within a
      population) and diagnostic strategy (amount of stool examined (~sensitivity of
      the diagnostic technique) and examination of individual/pooled stool samples) and
      on how to estimate prevalence of STH in the absence of a gold standard. To give
      these applications the most wide relevance as possible, we illustrate each of
      them with hypothetical examples. 

PMID- 25765197
TI  - Modelling lymphatic filariasis transmission and control: modelling frameworks,
      lessons learned and future directions.
AB  - Mathematical modelling provides a useful tool for policy making and planning in
      lymphatic filariasis control programmes, by providing trend forecasts based on
      sound scientific knowledge and principles. This is now especially true, in view
      of the ambitious target to eliminate lymphatic filariasis as a public health
      problem globally by the year 2020 and the short remaining timeline to achieve
      this. To meet this target, elimination programmes need to be accelerated,
      requiring further optimization of strategies and tailoring to local
      circumstances. Insights from epidemiological transmission models provide a useful
      basis. Two general models of lymphatic filariasis transmission and control are
      nowadays in use to support decision-making, namely a population-based
      deterministic model (EPIFIL) and an individual-based stochastic model (LYMFASIM).
      Model predictions confirm that lymphatic filariasis transmission can be
      interrupted by annual mass drug administration (MDA), but this may need to be
      continued much longer than the initially suggested 4-6 years in areas with high
      transmission intensity or poor treatment coverage. However, the models have not
      been validated against longitudinal data describing the impact of MDA programmes.
      Some critical issues remain to be incorporated in one or both of the models to
      make predictions on elimination more realistic, including the possible occurrence
      of systematic noncompliance, the risk of emerging parasite resistance to
      anthelmintic drugs, and spatial heterogeneities. Rapid advances are needed to
      maximize the utility of models in decision-making for the ongoing ambitious
      lymphatic filariasis elimination programmes. 

PMID- 25765198
TI  - Modelling the effects of mass drug administration on the molecular epidemiology
      of schistosomes.
AB  - As national governments scale up mass drug administration (MDA) programs aimed to
      combat neglected tropical diseases (NTDs), novel selection pressures on these
      parasites increase. To understand how parasite populations are affected by MDA
      and how to maximize the success of control programmes, it is imperative for
      epidemiological, molecular and mathematical modelling approaches to be combined.
      Modelling of parasite population genetic and genomic structure, particularly of
      the NTDs, has been limited through the availability of only a few molecular
      markers to date. The landscape of infectious disease research is being
      dramatically reshaped by next-generation sequencing technologies and our
      understanding of how repeated selective pressures are shaping parasite
      populations is radically altering. Genomics can provide high-resolution data on
      parasite population structure, and identify how loci may contribute to key
      phenotypes such as virulence and/or drug resistance. We discuss the incorporation
      of genetic and genomic data, focussing on the recently sequenced Schistosoma
      spp., into novel mathematical transmission models to inform our understanding of
      the impact of MDA and other control methods. We summarize what is known to date,
      the models that exist and how population genetics has given us an understanding
      of the effects of MDA on the parasites. We consider how genetic and genomic data
      have the potential to shape future research, highlighting key areas where data
      are lacking, and how future molecular epidemiology knowledge can aid
      understanding of transmission dynamics and the effects of MDA, ultimately
      informing public health policy makers of the best interventions for NTDs. 

PMID- 25765199
TI  - Economic and financial evaluation of neglected tropical diseases.
AB  - Economic and financing studies are particularly important for decision-making
      when resources are scarce or considerably limited. This is the case for neglected
      tropical diseases (NTDs). In fact, the definition of NTDs is an economic one. The
      shortage of resources for NTD control may be due in large part to the fact that
      the burden of NTDs and economic value of control measures have not been fully
      characterized. A number of economic study methodologies are available: cost of
      illness can quantify the extent, magnitude, and change of a problem; cost of
      intervention studies can outline the feasibility and guide the design of a policy
      or intervention; and cost-benefit, cost-effectiveness, and return-on-investment
      studies can determine the potential value of different interventions and
      policies. NTDs have unique characteristics that require special consideration in
      such analyses. Hence, approaches used for other diseases may need modifications
      to capture the full impact of NTDs. While the existing literature has made
      important findings, there is a need for substantially more work, as many NTDs and
      their associated interventions and policies require more evaluation. With
      increasing work in this area, NTDs may not be as 'neglected' in the future as
      they are now. 

PMID- 25765200
TI  - Corrigendum: an error-resilient non-volatile magneto-elastic universal logic gate
      with ultralow energy-delay product.

PMID- 25765202
TI  - Antibacterial immunity: a pinch of salt.

PMID- 25765201
TI  - Advancing host-directed therapy for tuberculosis.
AB  - Improved treatments are needed for nearly all forms of Mycobacterium tuberculosis
      infection. Adjunctive host-directed therapies have the potential to shorten
      tuberculosis treatment duration, prevent resistance and reduce lung injury by
      promoting autophagy, antimicrobial peptide production and other macrophage
      effector mechanisms, as well as by modifying specific mechanisms that cause lung
      inflammation and matrix destruction. The range of candidates is broad, including
      several agents approved for other clinical indications that are ready for
      evaluation in Phase II clinical trials. The promise of new and existing host
      directed therapies that could accelerate response and improve tuberculosis
      treatment outcomes is discussed in this Opinion article. 

PMID- 25765205
TI  - Highly transparent triboelectric nanogenerator for harvesting water-related
      energy reinforced by antireflection coating.
AB  - Water-related energy is an inexhaustible and renewable energy resource in our
      environment, which has huge amount of energy and is not largely dictated by
      daytime and sunlight. The transparent characteristic plays a key role in
      practical applications for some devices designed for harvesting water-related
      energy. In this paper, a highly transparent triboelectric nanogenerator (T-TENG)
      was designed to harvest the electrostatic energy from flowing water. The
      instantaneous output power density of the T-TENG is 11.56 mW/m(2). Moreover, with
      the PTFE film acting as an antireflection coating, the maximum transmittance of
      the fabricated T-TENG is 87.4%, which is larger than that of individual glass
      substrate. The T-TENG can be integrated with silicon-based solar cell, building
      glass and car glass, which demonstrates its potential applications for harvesting
      waste water energy in our living environment and on smart home system and smart
      car system.

PMID- 25765203
TI  - Longitudinal weight differences, gene expression and blood biomarkers in BMI
      discordant identical twins.
AB  - BACKGROUND: Body mass index (BMI) discordant monozygotic (MZ) twins allow an
      examination of the causes and consequences of adiposity in a genetically
      controlled design. Few studies have examined longitudinal BMI discordance in MZ
      pairs. OBJECTIVES: The aim of this work was to study the development over time of
      BMI discordance in adolescent and adult MZ twin pairs and to examine lifestyle,
      metabolic, inflammatory and gene expression differences associated with
      concurrent and long-term BMI discordance in MZ pairs. SUBJECTS/METHODS: BMI data
      from 2775 MZ twin pairs, collected in eight longitudinal surveys and a biobank
      project between 1991 and 2011, were analyzed to characterize longitudinal
      discordance. Lifestyle characteristics were compared within discordant pairs
      (DeltaBMI?3 kg m(-2)) and biomarkers (lipids, glucose, insulin, C-reactive
      protein, fibrinogen, interleukin (IL)-6, tumor necrosis factor-alpha and soluble
      IL-6 receptor and liver enzymes aspartate aminotransferase, alanine
      aminotransferase and gamma glutamyl transferase) and gene expression were
      compared in peripheral blood from discordant pairs who participated in the
      Netherlands Twin Register biobank project. RESULTS: The prevalence of discordance
      ranged from 3.2% in 1991 (mean age=17, s.d.=2.4) to 17.4% (N=202 pairs) in 2009
      (mean age=35, s.d.=15) and was 16.5% (N=174) among pairs participating in the
      biobank project (mean age=35, s.d.=12). Of the 699 MZ pairs with BMI data from 3
      to 5 time points, 17 pairs (2.4%) were long-term discordant (at all available
      time points; mean follow-up range=6.4 years). Concurrently discordant pairs
      showed significant differences in self-ratings of which twin eats most (P=2.3 *
      10(-13)) but not in leisure time exercise activity (P=0.28) and smoking (P>0.05).
      Ten out of the 14 biomarkers showed significantly more unfavorable levels in the
      heavier of twin of the discordant pairs (P-values <0.001); most of these
      biomarker differences were largest in longitudinally discordant pairs. No
      significant gene expression differences were identified, although high ranking
      genes were enriched for Gene Ontology terms highlighting metabolic gene
      regulation and inflammation pathways. CONCLUSIONS: BMI discordance is uncommon in
      adolescent identical pairs but increases with higher pair-mean of BMI at older
      ages, although long-term BMI discordance is rare. In discordant pairs, the
      heavier twin had a more unfavorable blood biomarker profile than the genetically
      matched leaner twin, in support of causal effects of obesity.

PMID- 25765206
TI  - How insurance affects altruistic provision in threshold public goods games.
AB  - The occurrence and maintenance of cooperative behaviors in public goods systems
      have attracted great research attention across multiple disciplines. A threshold
      public goods game requires a minimum amount of contributions to be collected from
      a group of individuals for provision to occur. Here we extend the common binary
      strategy combination of cooperation and defection by adding a third strategy,
      called insured cooperation, which corresponds to buying an insurance covering the
      potential loss resulted from the unsuccessful public goods game. Particularly,
      only the contributing agents can opt to be insured, which is an effort decreasing
      the amount of the potential loss occurring. Theoretical computations suggest that
      when agents face the potential aggregate risk in threshold public goods games,
      more contributions occur with increasing compensation from insurance. Moreover,
      permitting the adoption of insurance significantly enhances individual
      contributions and facilitates provision, especially when the required threshold
      is high. This work also relates the strategy competition outcomes to different
      allocation rules once the resulted contributions exceed the threshold point in
      populations nested within a dilemma. 

PMID- 25765207
TI  - Towards tissue-specific pharmacology: insights from the calcium-sensing receptor
      as a paradigm for GPCR (patho)physiological bias.
AB  - The calcium-sensing receptor (CaSR) is a widely expressed G protein-coupled
      receptor (GPCR) that mediates numerous tissue-specific functions. Its multiple
      ligands and diverse roles attest to the need for exquisite control over the
      signaling pathways that mediate its effects. 'Biased signaling' is the phenomenon
      by which distinct ligands stabilize preferred receptor signaling states. The CaSR
      is subject to biased signaling in response to its endogenous ligands.
      Interestingly, the 'natural' bias of the CaSR is altered in disease states, and
      small molecule drugs engender biased allosteric modulation of downstream
      signaling pathways. Thus, biased signaling from the CaSR also has important
      implications pathophysiologically and therapeutically. As outlined in this
      review, this novel paradigm extends to other GPCRs, making the CaSR a model for
      studies of ligand-biased signaling and for understanding how it may be used to
      foster selective drug activity in different tissues.

PMID- 25765208
TI  - From basilar artery dolichoectasia to basilar artery aneurysm: natural history in
      images.
AB  - Dolichoectasia is a medical term used to describe elongated and dilated vessels
      that follow a tortuous and windy course with frequent loops and curves. We are
      presenting the natural history in images of a normal basilar artery becoming
      dolichoectatic, followed by the formation of an aneurysm, over a period of many
      years, in 60-year-old Caucasian man with a long history of secondary progressive
      multiple sclerosis and uncontrolled arterial hypertension, who was diagnosed with
      dolichoectasia of basilar artery in 2008. Although relatively stable at this
      point, eventually his mobility deteriorated and signs from the cranial nerves,
      such as trigeminal neuralgia and bilateral palsy of the VI and the VII nerves
      were added in the clinical picture. In 2014, both computed tomography and
      magnetic resonance imaging of the brain revealed the formation of an unruptured
      aneurysm of the basilar artery. 

PMID- 25765209
TI  - Words of wisdom. Re: Salvage focal prostate cryoablation for locally recurrent
      prostate cancer after radiotherapy: initial results from the cryo on-line data
      registry.

PMID- 25765210
TI  - Words of wisdom. Re: Testosterone treatment is a potent tumor promoter for the
      rat prostate.

PMID- 25765211
TI  - Words of wisdom. Re: The effect of restaging transurethral resection on
      recurrence and progression rates in patients with nonmuscle invasive bladder
      cancer treated with intravesical bacillus Calmette-Guerin.

PMID- 25765212
TI  - Words of wisdom. Re: Safety, activity, and immune correlates of anti-PD-1
      antibody in cancer.

PMID- 25765213
TI  - Words of wisdom. Re: Intrathecal administration of botulinum toxin type a
      improves urinary bladder function and reduces pain in rats with cystitis.

PMID- 25765214
TI  - Words of wisdom. Re: 5-year longitudinal followup after retropubic and
      transobturator mid urethral slings.

PMID- 25765215
TI  - Corrigendum to "Immunoglobulin G4-related disease in genitourinary organs: an
      emerging fibroinflammatory entity often misdiagnosed preoperatively as cancer"
      [Eur Urol 2013;64:865-72].

PMID- 25765216
TI  - Genetic diversity and trait genomic prediction in a pea diversity panel.
AB  - BACKGROUND: Pea (Pisum sativum L.), a major pulse crop grown for its protein-rich
      seeds, is an important component of agroecological cropping systems in diverse
      regions of the world. New breeding challenges imposed by global climate change
      and new regulations urge pea breeders to undertake more efficient methods of
      selection and better take advantage of the large genetic diversity present in the
      Pisum sativum genepool. Diversity studies conducted so far in pea used Simple
      Sequence Repeat (SSR) and Retrotransposon Based Insertion Polymorphism (RBIP)
      markers. Recently, SNP marker panels have been developed that will be useful for
      genetic diversity assessment and marker-assisted selection. RESULTS: A collection
      of diverse pea accessions, including landraces and cultivars of garden, field or
      fodder peas as well as wild peas was characterised at the molecular level using
      newly developed SNP markers, as well as SSR markers and RBIP markers. The three
      types of markers were used to describe the structure of the collection and
      revealed different pictures of the genetic diversity among the collection. SSR
      showed the fastest rate of evolution and RBIP the slowest rate of evolution,
      pointing to their contrasted mode of evolution. SNP markers were then used to
      predict phenotypes -the date of flowering (BegFlo), the number of seeds per plant
      (Nseed) and thousand seed weight (TSW)- that were recorded for the collection.
      Different statistical methods were tested including the LASSO (Least Absolute
      Shrinkage ans Selection Operator), PLS (Partial Least Squares), SPLS (Sparse
      Partial Least Squares), Bayes A, Bayes B and GBLUP (Genomic Best Linear Unbiased
      Prediction) methods and the structure of the collection was taken into account in
      the prediction. Despite a limited number of 331 markers used for prediction, TSW
      was reliably predicted. CONCLUSION: The development of marker assisted selection
      has not reached its full potential in pea until now. This paper shows that the
      high-throughput SNP arrays that are being developed will most probably allow for
      a more efficient selection in this species.

PMID- 25765217
TI  - Burden of tuberculosis at post mortem in inpatients at a tertiary referral centre
      in sub-Saharan Africa: a prospective descriptive autopsy study.
AB  - BACKGROUND: Patients with subclinical tuberculosis, smear-negative tuberculosis,
      extrapulmonary tuberculosis, multidrug-resistant tuberculosis, and asymptomatic
      tuberculosis are difficult to diagnose and may be missed at all points of health
      care. We did an autopsy study to ascertain the burden of tuberculosis at post
      mortem in medical inpatients at a tertiary care hospital in Lusaka, Zambia.
      METHODS: Between April 5, 2012, and May 22, 2013, we did whole-body autopsies on
      inpatients aged at least 16 years who died in the adult inpatient wards at
      University Teaching Hospital, Lusaka, Zambia. We did gross pathological and
      histopathological analysis and processed lung tissues from patients with
      tuberculosis through the GeneXpert MTB/RIF assay to identify patients with
      multidrug-resistant tuberculosis. The primary outcome measure was specific
      disease or diseases stratified by HIV status. Secondary outcomes were missed
      tuberculosis, multidrug-resistant tuberculosis, and comorbidities with
      tuberculosis. Data were analysed using Pearson chi(2), the Mann-Whitney U test,
      and binary logistic regression. FINDINGS: The median age of the 125 included
      patients was 35 years (IQR 29-43), 80 (64%) were men, and 101 (81%) were HIV
      positive. 78 (62%) patients had tuberculosis, of whom 66 (85%) were infected with
      HIV. 35 (45%) of these 78 patients had extrapulmonary tuberculosis. The risk of
      extrapulmonary tuberculosis was higher among HIV-infected patients than among
      uninfected patients (adjusted odds ratio 5.14, 95% CI 1.04-24.5; p=0.045). 20
      (26%) of 78 patients with tuberculosis were not diagnosed during their life and
      13 (17%) had undiagnosed multidrug-resistant tuberculosis. Common comorbidities
      with tuberculosis were pyogenic pneumonia in 26 patients (33%) and anaemia in 15
      (19%). INTERPRETATION: Increased clinical awareness and more proactive screening
      for tuberculosis and multidrug-resistant tuberculosis in inpatient settings is
      needed. Further autopsy studies are needed to ascertain the generalisability of
      the findings. FUNDING: UBS Optimus Foundation, EuropeAID, and European Developing
      Countries Clinical Trials Partnership (EDCTP).

PMID- 25765218
TI  - Autopsies and better data on causes of death in Africa.

PMID- 25765219
TI  - Heritable influences on behavioural problems from early childhood to mid
      adolescence: evidence for genetic stability and innovation.
AB  - BACKGROUND: Although behavioural problems (e.g., anxiety, conduct, hyperactivity,
      peer problems) are known to be heritable both in early childhood and in
      adolescence, limited work has examined prediction across these ages, and none
      using a genetically informative sample. METHOD: We examined, first, whether
      parental ratings of behavioural problems (indexed by the Strengths and
      Difficulties questionnaire) at ages 4, 7, 9, 12, and 16 years were stable across
      these ages. Second, we examined the extent to which stability reflected genetic
      or environmental effects through multivariate quantitative genetic analysis on
      data from a large (n > 3000) population (UK) sample of monozygotic and dizygotic
      twins. RESULTS: Behavioural problems in early childhood (age 4 years) showed
      significant associations with the corresponding behavioural problem at all
      subsequent ages. Moreover, stable genetic influences were observed across ages,
      indicating that biological bases underlying behavioural problems in adolescence
      are underpinned by genetic influences expressed as early as age 4 years. However,
      genetic and environmental innovations were also observed at each age. CONCLUSION:
      These observations indicate that genetic factors are important for understanding
      stable individual differences in behavioural problems across childhood and
      adolescence, although novel genetic influences also facilitate change in such
      behaviours.

PMID- 25765221
TI  - Impact of body mass on job quality.
AB  - The current study explores the association between body mass and job quality, a
      composite measurement of job characteristics, for adults. We use nationally
      representative data from the Korean Labor and Income Panel Study for the years
      2005, 2007, and 2008 with 7282 person-year observations for men and 4611 for
      women. A Quality of Work Index (QWI) is calculated based on work content, job
      security, the possibilities for improvement, compensation, work conditions, and
      interpersonal relationships at work. The key independent variable is the body
      mass index (kg/m(2)) splined at 18.5, 25, and 30. For men, BMI is positively
      associated with the QWI only in the normal weight segment (+0.19 percentage
      points at the 10th, +0.28 at the 50th, +0.32 at the 75th, +0.34 at the 90th, and
      +0.48 at the 95th quantiles). A unit increase in the BMI for women is associated
      with a lower QWI at the lower quantiles in the normal weight segment (-0.28 at
      the 5th, -0.19 at the 10th, and -0.25 percentage points at the 25th quantiles)
      and at the upper quantiles in the overweight segment (-1.15 at the 90th and -1.66
      percentage points at the 95th quantiles). The results imply a spill-over cost of
      overweight or obesity beyond its impact on health in terms of success in the
      labor market. 

PMID- 25765220
TI  - The XX Sex Chromosome Complement is Required in Male and Female Mice for
      Enhancement of Immunity Induced by Exposure to 3,4-Dichloropropionanilide.
AB  - PROBLEM: The chemical propanil enhances antibody responses to a heat-killed
      Streptococcus pneumoniae (HKSP) vaccine. The enhanced response is dependent on
      gonads in females, but independent of gonads in males. The sex differences in the
      immune response may be due to sexual differentiation of the immune system or sex
      chromosome complement. METHOD OF STUDY: To test the hypothesis that the immune
      system is sexually differentiated, newborn C57BL/6 pups were treated with
      testosterone propionate (TP) or placebo. The role of sex chromosome complement
      was investigated using the 4-core genotypes (FCG) model of XXF and XYF gonadal
      females (ovaries), and XXM and XYM gonadal males (testes). For some experiments,
      mice were gonadectomized or sham gonadectomized. All mice were vaccinated with
      HKSP, treated with propanil, and the antibody response determined at day seven.
      RESULTS: Neonatal TP did not alter the response to HKSP. In FCG mice, propanil
      significantly enhanced the immune response in XXF females and XXM males, but not
      in XYF females or XYM males. CONCLUSION: The immune system of females was not
      masculinized by neonatal TP treatment. Sex chromosome complement significantly
      contributes to the sexually dimorphic immune response after propanil exposure.

PMID- 25765222
TI  - Mechanism of visible light photocatalytic NO(x) oxidation with plasmonic Bi
      cocatalyst-enhanced (BiO)2CO3 hierarchical microspheres.
AB  - Semimetal bismuth (Bi), as an emerging non-noble metal-based cocatalyst and
      plasmonic photocatalyst, has attracted significant attention. In this work, a one
      pot solvent-controlled synthesis strategy was utilized for the in situ-deposition
      of plasmonic Bi nanoparticles onto the surfaces of (BiO)2CO3 microspheres (BOC
      WE) using bismuth citrate, sodium carbonate, and ethylene glycol as precursors.
      The introduction of the Bi nanoparticles has a pivotal effect on the morphology,
      optical and photocatalytic performance of the pristine (BiO)2CO3. The results
      indicated that the Bi nanoparticles were generated on the surface of (BiO)2CO3
      microspheres via the in situ reduction of Bi(3+) by ethylene glycol. The Bi
      deposited (BiO)2CO3 microspheres were used for the photocatalytic purification of
      NOx in air under visible light irradiation. Significantly, the BOC-WE samples
      exhibited a drastically promoted photocatalytic performance with a NOx removal
      ratio (eta) of 37.2%, superior to pristine (BiO)2CO3 (eta = 19.1%), outperforming
      other well-known visible light photocatalysts, such as C-doped TiO2 (eta =
      21.8%), BiOBr (eta = 21.3%), BiOI (eta = 14.9%) and C3N4 (eta = 25.5%). The
      conspicuously enhanced photocatalytic capability can be attributed to the
      synergistic effects of the surface plasmon resonance (SPR) effect, increased
      visible light absorption and the efficient separation of electron-hole pairs
      induced by the Bi nanoparticles. The Bi nanoparticles can act as a non-noble
      metal-based cocatalyst for strengthening photocatalytic performance, which is
      similar to the behavior of noble metals (Au, Ag) in enhancing photocatalysis. The
      mechanism of visible light photocatalytic NOx oxidation was investigated. DMPO
      ESR spin-trapping results demonstrated that hydroxyl radicals were confirmed to
      be the main active species for NOx photo-oxidation. Due to the SPR effect of Bi,
      the BOC-WE could produce more hydroxyl radicals than BOC, which was responsible
      for the enhanced NO photo-oxidation ability. Moreover, the BOC-WE photocatalysts
      showed high photochemical stability under repeated irradiation. This work
      demonstrates the feasibility of utilizing low cost Bi cocatalysts as a substitute
      for noble metals to enhance the performance of other photocatalysts. This work
      could not only provide new insights into the in situ fabrication of
      Bi/semiconductor nanocomposites, but also pave a new way for the modification of
      photocatalysts with non-noble metals as cocatalysts to achieve an enhanced
      performance for environmental and energetic applications. 

PMID- 25765223
TI  - Hypervalent iodine mediated alkene difunctionalization of vinylphenols:
      diastereoselective synthesis of substituted indoles and indolizines.
AB  - A hypervalent iodine mediated alkene difunctionalization reaction of vinylphenols
      has been developed. The chemistry is applicable to a wide range of substitutions
      on both the alkene and nucleophile substrates, enabling the rapid synthesis of 3
      substituted indoles and 2-substituted indolizines in good yields and high
      diastereoselectivities under metal-free conditions. 

PMID- 25765225
TI  - Challenges in diagnosing infection in the diabetic foot.
AB  - Diagnosing the presence of infection in the foot of a patient with diabetes can
      sometimes be a difficult task. Because open wounds are always colonized with
      microorganisms, most agree that infection should be diagnosed by the presence of
      systemic or local signs of inflammation. Determining whether or not infection is
      present in bone can be especially difficult. Diagnosis begins with a history and
      physical examination in which both classic and 'secondary' findings suggesting
      invasion of microorganisms or a host response are sought. Serological tests may
      be helpful, especially measurement of the erythrocyte sedimentation rate in
      osteomyelitis, but all (including bone biomarkers and procalcitonin) are
      relatively non-specific. Cultures of properly obtained soft tissue and bone
      specimens can diagnose and define the causative pathogens in diabetic foot
      infections. Newer molecular microbial techniques, which may not only identify
      more organisms but also virulence factors and antibiotic resistance, look very
      promising. Imaging tests generally begin with plain X-rays; when these are
      inconclusive or when more detail of bone or soft tissue abnormalities is
      required, more advanced studies are needed. Among these, magnetic resonance
      imaging is generally superior to standard radionuclide studies, but newer hybrid
      imaging techniques (single-photon emission computed tomography/computed
      tomography, positron emission tomography/computed tomography and positron
      emission tomography/magnetic resonance imaging) look to be useful techniques, and
      new radiopharmaceuticals are on the horizon. In some cases, ultrasonography,
      photographic and thermographic methods may also be diagnostically useful.
      Improved methods developed and tested over the past decade have clearly increased
      our accuracy in diagnosing diabetic foot infections. 

PMID- 25765224
TI  - Synthesis of 2-anilinopyridyl-triazole conjugates as antimitotic agents.
AB  - A series of 2-anilinopyridyl-triazole conjugates (6a-t) were prepared and
      evaluated for their cytotoxic activity against a panel of three human cancer cell
      lines. Among them compounds 6q, 6r and 6s showed significant cytotoxic activity
      with IC50 values ranging from 0.1 to 4.1 MUM. Structure-activity relationships
      were elucidated with various substitutions on these conjugates. Flow cytometric
      analysis revealed that these compounds arrest the cell cycle at the G2/M phase
      and induce cell death by apoptosis. The tubulin polymerization assay and
      immunofluorescence analysis showed that these compounds (6q, 6r and 6s)
      effectively inhibited the microtubule assembly in human prostate cancer cells (DU
      145). The docking studies showed that 6s interacts and binds efficiently with the
      tubulin protein at the colchicine binding site. This was further confirmed by the
      colchicine competitive binding assay. Moreover, compounds 6q, 6r and 6s possess
      anti-tubulin activity both in vitro and within cells as demonstrated by the ratio
      of soluble versus polymerized tubulin. Further the apoptotic effects of compounds
      were confirmed by Hoechst staining, caspase 3 activation, annexin-V FITC,
      mitochondrial membrane potential and DNA fragmentation analysis. Interestingly,
      these compounds did not affect the normal human embryonic kidney cells, HEK-293.

PMID- 25765226
TI  - Factors influencing student nurse decisions to report poor practice witnessed
      while on placement.
AB  - BACKGROUND: While it is commonly accepted that nursing care is generally of a
      good standard, it would be naive to think that this is always the case. Over
      recent years, concern about aspects of the quality of some nursing care has
      grown. In tandem with this, there is recognition that nurses do not always report
      poor practice. As future registrants, student nurses have a role to play in
      changing this culture. We know, however, relatively little about the factors that
      influence student decisions on whether or not to report. In the absence of a more
      nuanced understanding of this issue, we run the risk of assuming students will
      speak out simply because we say they should. OBJECTIVES: To explore influences on
      student decisions about whether or not to report poor clinical practice, which is
      a result of deliberate action and which is witnessed while on placement. METHODS:
      Qualitative interviews were conducted with thirteen pre-registration nursing
      students from the UK. Participants included both adult and mental health nurses
      with an age range from 20 to 47. Data were analysed to identify key themes.
      Category integrity and fit with data were confirmed by a team member following
      initial analysis. RESULTS: Four themes. The first of these, 'I had no choice'
      described the personal and ethical drivers which influenced students to report.
      'Consequences for self' and 'Living with ambiguity' provide an account of why
      some students struggle to report, while 'Being prepared' summarised arguments
      both for and against reporting concerns. CONCLUSION: While there is a drive to
      promote openness in health care settings and an expectation that staff will raise
      concerns the reality is that the decision to do this can be very difficult. This
      is the case for some student nurses. Our results suggest ways in which
      educationalists might intervene to support students who witness poor practice to
      report.

PMID- 25765227
TI  - Striving for evidence-based practice innovations through a hybrid model journal
      club: A pilot study.
AB  - OBJECTIVE: The purpose of this study was to pilot a "hybrid" style journal club
      and determine whether measurable effects could be detected over 8-weeks' time on
      evidence-based practice ability, desire, behaviors, use, and barriers.
      BACKGROUND: Journal clubs have been suggested as a method to increase nurses'
      confidence with using research evidence to guide practice. However, it is yet
      unknown how nurse educators can best implement effective programs for clinicians
      with varying schedules, education levels, and research skills. SETTING AND
      PARTICIPANTS: Thirty-six participants from one large urban United States hospital
      (72% registered nurses) were invited to access bi-weekly interdisciplinary
      journal club activities. Nurse educators created curriculum focused on clinical
      problem solving that was offered via in-person sessions or a social media site.
      METHODS: A pretest-posttest no control group design was used to measure impacts
      of those engaged in journal club activities. Data were collected using a
      combination of validated evidence-based practice instruments and program
      participation records. FINDINGS: A two-tailed paired t test showed significant
      increases over 8weeks' time in evidence-based practice use (p=.002) and behaviors
      (p=.007). Slight preference for in-person sessions was reported, although greater
      participation was reflected in online activities. Mean satisfaction ratings were
      high; however, attrition rates suggest that more is needed to maximize clinician
      engagement. CONCLUSION: A hybrid method using online and in-person sessions was
      feasible and adaptive for varying learning styles and work schedules. Positive
      changes in measurements were detected among journal club participants.
      Instruments were identified that may be useful for trialing similar programs
      intended to increase evidence-based practice self-efficacy, use, behaviors, and
      ability.

PMID- 25765228
TI  - Friedreich's Ataxia (FRDA) is an extremely rare cause of autosomal recessive
      ataxia in Chinese Han population.
AB  - Friedreich's Ataxia (FRDA) is a very common cause of hereditary autosomal
      recessive ataxia among western Europeans. We aim to define the frequency of FRDA
      in Chinese Han population due to the lack of reports of FRDA in China. The GAA
      trinucleotide repeats in the FXN gene were analyzed by triplet repeat-primed PCR
      (TP-PCR) in 122 unrelated hereditary ataxia (HA) and 114 unrelated hereditary
      spastic paraplegia (HSP) patients. The GAA copy numbers in the FXN gene of all
      the subjects ranged from 5 to 16. There were no FRDA patients that could be
      diagnosed base on the results of TP-PCR. It suggests that FRDA is a very rare
      cause of inheritance ataxia and FRDA genetic analysis should not be used as a
      routine genetic diagnosis test in China. 

PMID- 25765229
TI  - Statin induced necrotizing autoimmune myopathy.
AB  - Statin induced necrotizing autoimmune myopathy (SINAM) is a recently
      characterized entity belonging to the spectrum of statin myotoxicity. It is a
      more severe form, and is usually associated with significant proximal muscle
      weakness, strikingly elevated creatine kinase levels and persistent symptoms
      despite statin discontinuation. The characteristic pathological finding is a
      marked muscle fiber necrosis with minimal or no inflammation on muscle biopsy.
      SINAM is an autoimmune disorder associated with an antibody against 3-hydroxy-3
      methyglutaryl-coenzyme A reductase (HMGCR), and the antibody titer is a useful
      marker for assessing treatment response. However, anti-HMGCR positive myopathies
      are also caused by unknown etiologies other than statin exposure, especially in
      the younger population. SINAM should be promptly recognized as immunosuppressive
      therapy can improve its clinical outcome significantly. Further research is
      needed to elucidate its pathogenesis and provide evidence based guidelines for
      management. 

PMID- 25765230
TI  - A logical data representation framework for electricity-driven bioproduction
      processes.
AB  - Microbial electrosynthesis (MES) is a process that uses electricity as an energy
      source for driving the production of chemicals and fuels using microorganisms and
      CO2 or organics as carbon sources. The development of this highly
      interdisciplinary technology on the interface between biotechnology and
      electrochemistry requires knowledge and expertise in a variety of scientific and
      technical areas. The rational development and commercialization of MES can be
      achieved at a faster pace if the research data and findings are reported in
      appropriate and uniformly accepted ways. Here we provide a framework for
      reporting on MES research and propose several pivotal performance indicators to
      describe these processes. Linked to this study is an online tool to perform
      necessary calculations and identify data gaps. A key consideration is the
      calculation of effective energy expenditure per unit product in a manner enabling
      cross comparison of studies irrespective of reactor design. We anticipate that
      the information provided here on different aspects of MES ranging from reactor
      and process parameters to chemical, electrochemical, and microbial functionality
      indicators will assist researchers in data presentation and ease data
      interpretation. Furthermore, a discussion on secondary MES aspects such as
      downstream processing, process economics and life cycle analysis is included. 

PMID- 25765231
TI  - Synthesis of cubic PtPd alloy nanoparticles as anode electrocatalysts for
      methanol and formic acid oxidation reactions.
AB  - The electrocatalytic properties for electro-oxidation reactions of shape
      controlled Pt-based catalysts have been improved by alloying with 2nd elements.
      In this study, we demonstrate cubic PtPd alloy nanoparticles synthesized using a
      thermal decomposition method. The cubic PtPd nanoparticles exhibit a homogeneous
      distribution of alloy nanostructures in the presence of Pt and Pd metallic
      phases. The improved electrocatalytic activity for the electro-oxidation
      reactions of methanol and formic acid as chemical fuels might be attributed to
      the cubic alloy nanostructures. Furthermore, the cubic PtPd alloy nanoparticles
      as electrocatalysts exhibit excellent stability for electro-oxidation reactions. 

PMID- 25765232
TI  - Ni-Catalyzed direct 1,4-difunctionalization of [60]fullerene with benzyl
      bromides.
AB  - A new Ni-catalyzed direct 1,4-difunctionalization of [60]fullerene with various
      benzyl bromides has been developed. The use of a DMSO additive combined with a
      nickel catalyst is indispensable for the formation of 1,4-dibenzyl fullerenes
      with a variety of functional groups. The reaction proceeds through the formation
      of a fullerene monoradical species. 

PMID- 25765233
TI  - Primary hepatic diffuse large B-cell lymphoma: unusual presentation and imaging
      features.
AB  - Primary hepatic lymphoma is an uncommon malignancy affecting the liver, with
      limited reports and series in the literature. Imaging appearance is not well
      described, with no definite features suggesting a diagnosis, and it may mimic
      other focal hepatic lesions. However, biopsy is needed in most of the cases for
      confirmation. We report a case of 22-year-old pregnant woman who on
      ultrasonography showed a large heteroechoic solitary liver mass mimicking focal
      nodular hyperplasia. Further evaluation after parturition with contrast-enhanced
      magnetic resonance imaging showed a large mass with central scar and peripheral
      diffusion restriction and contrast enhancement, which was atypical. Biopsy
      confirmed it as lymphoma. The case illustrates unusual presentation and magnetic
      resonance imaging features, including diffusion-weighted imaging, of primary
      hepatic lymphoma in a young female. 

PMID- 25765235
TI  - Pyoderma gangrenosum secondary to azacitidine in myelodysplastic syndrome.

PMID- 25765234
TI  - Genome-wide epistatic expression quantitative trait loci discovery in four human
      tissues reveals the importance of local chromosomal interactions governing gene
      expression.
AB  - BACKGROUND: Epistasis (synergistic interaction) among SNPs governing gene
      expression is likely to arise within transcriptional networks. However, the power
      to detect it is limited by the large number of combinations to be tested and the
      modest sample sizes of most datasets. By limiting the interaction search space
      firstly to cis-trans and then cis-cis SNP pairs where both SNPs had an
      independent effect on the expression of the most variable transcripts in the
      liver and brain, we greatly reduced the size of the search space. RESULTS: Within
      the cis-trans search space we discovered three transcripts with significant
      epistasis. Surprisingly, all interacting SNP pairs were located nearby each other
      on the chromosome (within 290 kb-2.16 Mb). Despite their proximity, the
      interacting SNPs were outside the range of linkage disequilibrium (LD), which was
      absent between the pairs (r(2) < 0.01). Accordingly, we redefined the search
      space to detect cis-cis interactions, where a cis-SNP was located within 10 Mb of
      the target transcript. The results of this show evidence for the epistatic
      regulation of 50 transcripts across the tissues studied. Three transcripts,
      namely, HLA-G, PSORS1C1 and HLA-DRB5 share common regulatory SNPs in the pre
      frontal cortex and their expression is significantly correlated. This pattern of
      epistasis is consistent with mediation via long-range chromatin structures rather
      than the binding of transcription factors in trans. Accordingly, some of the
      interactions map to regions of the genome known to physically interact in
      lymphoblastoid cell lines while others map to known promoter and enhancer
      elements. SNPs involved in interactions appear to be enriched for promoter
      markers. CONCLUSIONS: In the context of gene expression and its regulation, our
      analysis indicates that the study of cis-cis or local epistatic interactions may
      have a more important role than interchromosomal interactions.

PMID- 25765236
TI  - Challenges with Meta-Analysis in Deep Brain Stimulation.

PMID- 25765237
TI  - [Growth in steroid-responsive nephrotic syndrome in Cote d'Ivoire].
AB  - We realized one of the first observational studies in sub-Saharan Africa whose
      aim was to analyze the growth in steroid-responsive nephrotic syndrome. This was
      a retrospective study, involving 30 children followed for nephrotic syndrome in
      pediatric nephrology unit of the University Hospital of Yopougon (Abidjan) from
      28.02.2005 to 19.12.2010. Each child was followed for two years and we are
      interested in demographic characteristics and the evolution of size. At the end
      of our study, it appears that: the mean age was 89.33 +/- 43.41 months (7.44
      years) with a sex ratio of 3,28. At the end of the two years of follow-up,
      patients had received a median dose of steroids 6151 +/- 3832 mg/m(2), 9111 +/-
      1376 mg/m(2) and 8664 +/- 5379 mg/m(2), respectively, for a relapse or no, two
      and at least three relapses. Fourteen patients had received vitamin D therapy and
      calcium. At the end of follow-up, four children had growth retardation. An
      average gain in Z-score was noted at the end of follow-up in girls and boys
      respectively +0.06 and +0.36. The growth retardation observed in our study was
      not associated with different growth periods (P=0.116), gender (P=0.548) and the
      mean Z-scores observed at the end of follow-up was not significantly different
      between the sexes (P=0.26). Growth retardation observed was not related to the
      cumulative dose administered (P=0.15), number of relapse (P=1.000). 

PMID- 25765238
TI  - 5-Methyl phenazine-1-carboxylic acid: a novel bioactive metabolite by a
      rhizosphere soil bacterium that exhibits potent antimicrobial and anticancer
      activities.
AB  - A new rhizosphere soil bacterium that exhibits antimicrobial potential against
      human pathogens was isolated. On the basis of 16S ribosomal RNA nucleotide
      sequence homology and subsequent phylogenetic tree analysis, the strain PUW5 was
      identified as Pseudomonas putida. A bioactive metabolite was extracted and
      purified using silica gel column chromatography and preparative HPLC.
      Characterization of metabolite was done by employing Fourier transform infrared
      spectroscopy (FTIR), nuclear magnetic resonance (NMR) and mass spectroscopy (MS).
      On the basis of spectroscopic data, the metabolite was structurally elucidated as
      5-methyl phenazine-1-carboxylic acid betaine (MPCAB). The MPCAB exhibits
      selective cytotoxicity towards lung (A549) and breast (MDA MB-231) cancer cell
      lines in dose-dependent manner with IC50 value of 488.7+/-2.52 nM and 458.6+/
      2.48 nM respectively. The MPCAB exhibited inhibition of cell viability, DNA
      synthesis, induced G1 cell cycle arrest and apoptosis in cancer cells. The
      docking and interaction studies confirmed the binding potential of MPCAB with Bcl
      2 than Bcl-xL and Bcl-w proteins. These results strongly suggest that the MPCAB
      induces apoptosis in A549 and MDA MB-231 cancer cells through mitochondrial
      intrinsic pathway via activation of caspase-3 and down regulation of Bcl-2
      protein.

PMID- 25765240
TI  - Complex patients - complex DDI: is there a straight way forward?

PMID- 25765239
TI  - Tissue and species differences in the glucuronidation of glabridin with UDP
      glucuronosyltransferases.
AB  - Glabridin (GA) has gained wide application in the cosmetics and food industry.
      This study was performed to investigate its metabolic inactivation and
      elimination by glucuronidation by use of liver and intestine microsomes from
      humans (HLM and HIM) and rats (RLM and RIM), and liver microsomes from cynomolgus
      monkeys and beagle dogs (CyLM and DLM). Both hydroxyl groups at the C2 and C4
      positions of the B ring are conjugated to generate two mono-glucuronides (M1 and
      M2). HIM, RIM and RLM showed the most robust activity in catalyzing M2 formation
      with intrinsic clearance values (Clint) above 2000 MUL/min/mg, with little
      measurable M1 formation activity. DLM displayed considerable activity both in M1
      and M2 formation, with Clint values of 71 and 214 MUL/min/mg, respectively, while
      HLM and CyLM exhibited low activities in catalyzing M1 and M2 formation, with
      Clint values all below 20 MUL/min/mg. It is revealed that UGT1A1, 1A3, 1A9, 2B7,
      2B15 and extrahepatic UGT1A8 and 1A10 are involved in GA glucuronidation. Nearly
      all UGTs preferred M2 formation except for UGT1A1. Notably, UGT1A8 displayed the
      highest activity with a Clint value more than 5-fold higher than the other
      isoforms. Chemical inhibition studies, using selective inhibitors of UGT1A1, 1A9,
      2B7 and 1A8, further revealed that UGT1A8 contributed significantly to intestinal
      GA glucuronidation in humans. In summary, this in vitro study demonstrated large
      species differences in GA glucuronidation by liver and intestinal microsomes, and
      that intestinal UGTs are important for the pathway in humans.

PMID- 25765242
TI  - PROTEOMICS reviews 2015.

PMID- 25765246
TI  - Walther Nernst and the development of physical chemistry.
AB  - A commemorative symposium took place on the 16th June 2014 in the Magnus House in
      Berlin on the occasion of the 150th birthday of Walter Nernst. This Essay
      outlines the important stages in his life and consider the main features in the
      development of the discipline cofounded by him. 

PMID- 25765247
TI  - Inhibitory self-control moderates the effect of changed implicit food evaluations
      on snack food consumption.
AB  - The current study used a modified implicit association test (IAT) to change
      implicit evaluations of unhealthy snack food and tested its effects on subsequent
      consumption. Furthermore, we investigated whether these effects were moderated by
      inhibitory self-control. A sample of 148 women (17-25 years) motivated to manage
      weight through healthy eating completed an IAT intervention, and pre- and post
      intervention IATs assessing implicit evaluations of unhealthy food. The
      intervention IAT trained participants to pair unhealthy food stimuli with either
      positive or negative stimuli. A task disguised as a taste-test was used to assess
      consumption of unhealthy snack foods. Inhibitory self-control was measured using
      a self-report scale. As predicted, the implicit evaluation of unhealthy food
      became more negative from pre- to post-training among participants in the food
      negative pairing condition; however, there was no corresponding change in the
      food positive pairing condition. The effect of the training on snack consumption
      was moderated by inhibitory self-control with only participants low in inhibitory
      self-control having lower snack intake following the food negative training. This
      finding is consistent with dual-process models of behaviour which predict that
      self-control capacity renders impulses less influential on behaviour.
      Furthermore, it suggests that an intervention that retrains implicit food
      evaluations could be effective at reducing unhealthy eating, particularly among
      those with low inhibitory self-control.

PMID- 25765249
TI  - Shape Memory Hydrogel based on a Hydrophobically-Modified Polyacrylamide
      (HMPAM)/alpha-CD Mixture via a Host-Guest Approach.
AB  - A novel thermally sensitive shape memory (SM) hydrogel is prepared by block
      copoly-merization of a cationic surfactant monomer, dimethylhexadecyl[2
      (dimethylamino)ethylmethacrylate]ammoniumbromide (C(16)DMAEMA), and acrylamide
      (AM) in the presence of alpha-cyclodextrin (alpha-CD) using N,N'
      methylenebisacrylamide (MBA) as a crosslinker. XRD, solid state (13)C NMR, and
      DSC measurements show that the crystalline domains, induced by the hydrogen bonds
      between alpha-CDs threaded on the hydrophobic units of the polymer chains through
      the host-guest approach, can reversibly melt and crystallize at different
      temperatures. Rheological measurements show that both the elastic modulus G' and
      viscous modulus G'' drastically change due to the formation and dissolution of
      the crystalline domains. These thermo-sensitive crystalline domains serve as
      reversible physical crosslinks, endowing the hydrogel with excellent SM
      properties. Cyclic experiments show that the hydrogel can recover to almost 100%
      of the deformation in each cycle and can be reused several times.

PMID- 25765248
TI  - Increased 24-hour ad libitum food intake is associated with lower plasma irisin
      concentrations the following morning in adult humans.
AB  - BACKGROUND: The relationship between food intake and irisin concentrations in
      humans is unclear. OBJECTIVES: To determine whether the previous day's intake
      impacts fasting plasma irisin concentrations, or whether fasting irisin
      concentrations associate with subsequent ad libitum food intake. METHODS: Sixty
      six nondiabetic adults (42 men) were admitted for a study of the determinants of
      energy intake. After 6 days of a weight maintaining diet, ad libitum energy
      intake over 3 days was assessed using a vending machine paradigm. Fasting plasma
      irisin concentrations were measured on the morning of the second day of the
      vending period. RESULTS: There were no correlations between irisin and
      demographic or anthropometric parameters. On day 1, subjects consumed 144 +/- 52%
      of weight maintaining energy needs. Every additional 500 kcal consumed on day 1
      associated with a 3.4% lower irisin concentration the following morning (95% CI 
      6.2, -0.4%, p = 0.01; adjusted for age, sex and race). If energy intake was
      expressed as a percentage of weight maintaining energy needs, every 10% increase
      associated with a 1.9% lower irisin concentration (95% CI -3.7, -0.1%; adjusted p
      = 0.02). A 100 kcal increase in carbohydrate or fat consumption associated with a
      1.3% (95% CI -2.5, -0.1%, p = 0.01) and a 0.6% (95% CI -1.1, -0.0%, p = 0.02)
      lower irisin concentration, respectively. There was no association between
      fasting irisin concentrations and subsequent energy intake on day 2 (r = 0.19, p
      = 0.1). CONCLUSIONS: Higher ad libitum 24 h energy intake was associated with
      lower fasting irisin concentrations the following morning, but fasting irisin
      concentrations did not predict subsequent energy intake. The decrease in irisin
      concentrations with increased energy intake is consistent with the detrimental
      metabolic effects of overeating.

PMID- 25765250
TI  - Photochromism emergence in N-salicylidene p-aminobenzenesulfonate diallylammonium
      salts.
AB  - N-Salicylidene p-aminobenzenesulfonate salts were prepared by in situ
      condensation of p-aminobenzenesulfonate diallylammonium salt and salicylaldehyde.
      Modulation of thermo- and photochromism was achieved by varying the alkyl chain
      length of the diallylammonium counter-cation. A structural-optical properties
      investigation reveals that both crystal packing and dihedral angle between
      aromatic rings of the N-salicylidene aniline switch are not sufficient to predict
      the occurrence of photochromism in the solid state. The available free space
      around the N-salicylidene p-aminobenzenesulfonate, in addition to the flexibility
      of the nearby environment, is shown to be of major importance for the cis->trans
      isomerisation to occur as well as for the stabilisation of the trans-keto form.
      Emergence of photochromic properties was determined from the diallylhexylammonium
      cation within the series of investigated counter-cations. High stability is
      observed for the trans-keto form of one polymorph of N-salicylidene p
      aminobenzenesulfonate diallylhexylammonium salt (k = 2.4*10(-7)  s(-1)).

PMID- 25765251
TI  - Innate IgG molecules and innate B cells expressed by immunoglobulin constant
      heavy G chain (Fcgamma) genetic marker genes are involved in the 'allergic march'
      of IgE sensitization in children.
AB  - BACKGROUND: Interindividual variations of immunoglobulin constant heavy G chain
      (IGHG) genes on chromosome 14q32.3 are identified by alternative genetic markers
      (GM) of IgG3, IgG1 and IgG2, respectively. They express structurally and
      functionally innate IgG molecules and B cells, associated with allergic disease,
      replicated in several studies. MATERIALS AND METHODS: 1-year-old and 10-year-old,
      IgE-sensitized and non-sensitized children from the German Multicenter Allergy
      Study birth cohort were assessed by new serological methods for the mendelian
      IGHG (Fcgamma) (GM) genes, as innate IgG molecules and innate B cells. RESULTS:
      Food allergy sensitization in thirty-five 1-year-old children (124 not
      sensitized) was associated with the IGHG*bfn haplotype and B*(bfn) cells (OR 1.9,
      95% CI 1.2-3.1; p = 0.010). Aeroallergen sensitization in ninety-nine 10-year-old
      children (95 not sensitized) was associated with the same genes (OR 1.4, 95% CI
      1.02-1.9; p = 0.034). The IgE sensitization was most prominent in the restrictive
      homozygous IGHG*bfn/*bfn diplotype, 34% at age 1, increasing to 60% at age 10,
      rating the highest numbers of positive IgE tests, expressing increased levels of
      IgE and innate IgG2*n. CONCLUSIONS: The IGHG*bfn haplotype (B*(bfn) cells) and
      increased innate IgG2*n levels are predictive factors for IgE sensitization in
      childhood. IGHG genes can be assessed for prognostic and preventive purposes in
      clinical care.

PMID- 25765252
TI  - Bayesian sample sizes for exploratory clinical trials comparing multiple
      experimental treatments with a control.
AB  - In this paper, a Bayesian approach is developed for simultaneously comparing
      multiple experimental treatments with a common control treatment in an
      exploratory clinical trial. The sample size is set to ensure that, at the end of
      the study, there will be at least one treatment for which the investigators have
      a strong belief that it is better than control, or else they have a strong belief
      that none of the experimental treatments are substantially better than control.
      This criterion bears a direct relationship with conventional frequentist power
      requirements, while allowing prior opinion to feature in the analysis with a
      consequent reduction in sample size. If it is concluded that at least one of the
      experimental treatments shows promise, then it is envisaged that one or more of
      these promising treatments will be developed further in a definitive phase III
      trial. The approach is developed in the context of normally distributed responses
      sharing a common standard deviation regardless of treatment. To begin with, the
      standard deviation will be assumed known when the sample size is calculated. The
      final analysis will not rely upon this assumption, although the intended
      properties of the design may not be achieved if the anticipated standard
      deviation turns out to be inappropriate. Methods that formally allow for
      uncertainty about the standard deviation, expressed in the form of a Bayesian
      prior, are then explored. Illustrations of the sample sizes computed from the new
      method are presented, and comparisons are made with frequentist methods devised
      for the same situation.

PMID- 25765253
TI  - Monitoring Combretastatin A4-induced tumor hypoxia and hemodynamic changes using
      endogenous MR contrast and DCE-MRI.
AB  - PURPOSE: To benchmark MOBILE (Mapping of Oxygen By Imaging Lipid relaxation
      Enhancement), a recent noninvasive MR method of mapping changes in tumor hypoxia,
      electron paramagnetic resonance (EPR) oximetry, and dynamic contrast-enhanced MRI
      (DCE-MRI) as biomarkers of changes in tumor hemodynamics induced by the
      antivascular agent combretastatin A4 (CA4). METHODS: NT2 and MDA-MB-231 mammary
      tumors were implanted subcutaneously in FVB/N and nude NMRI mice. Mice received
      100 mg/kg of CA4 intraperitoneally 3 hr before imaging. The MOBILE sequence
      (assessing R1 of lipids) and the DCE sequence (assessing K(trans) hemodynamic
      parameter), were assessed on different cohorts. pO2 changes were confirmed on
      matching tumors using EPR oximetry consecutive to the MOBILE sequence. Changes in
      tumor vasculature were assessed using immunohistology consecutive to DCE-MRI
      studies. RESULTS: Administration of CA4 induced a significant decrease in lipids
      R1 (P = 0.0273) on pooled tumor models and a reduction in tumor pO2 measured by
      EPR oximetry. DCE-MRI also exhibited a significant drop of K(trans) (P < 0.01)
      that was confirmed by immunohistology. CONCLUSION: MOBILE was identified as a
      marker to follow a decrease in oxygenation induced by CA4. However, DCE-MRI
      showed a higher dynamic range to follow changes in tumor hemodynamics induced by
      CA4.

PMID- 25765254
TI  - Intermediate electrostatic field for the generalized elongation method.
AB  - An intermediate electrostatic field is introduced to improve the accuracy of
      fragment-based quantum-chemical computational methods by including long-range
      polarizations of biomolecules. The point charge distribution of the intermediate
      field is generated by a charge sensitivity analysis that is parameterized for
      five different population analyses, namely, atoms-in-molecules, Hirshfeld,
      Mulliken, natural orbital, and Voronoi population analysis. Two model systems are
      chosen to demonstrate the performance of the generalized elongation method (ELG)
      combined with the intermediate electrostatic field. The calculations are
      performed for the STO-3G, 6-31G, and 6-31G(d) basis sets and compared with
      reference Hartree-Fock calculations. It is shown that the error in the total
      energy is reduced by one order of magnitude, independently of the population
      analyses used. This demonstrates the importance of long-range polarization in
      electronic-structure calculations by fragmentation techniques. 

PMID- 25765255
TI  - Cataract surgery and intraocular pressure.
AB  - Cataract surgery is one of the most performed surgeries in the developed world.
      In addition to its significant impact on visual acuity, phacoemulsification has
      been hailed as a potential intraocular pressure (IOP)-lowering procedure. While
      current evidence suggests an overall significant and sustained decrease in IOP to
      exist after cataract surgery, the specific ocular characteristics that could help
      predict which patients are likely to benefit from this IOP-lowering effect remain
      unclear. This definition is important in glaucoma patients if this surgery is to
      be used in the treatment for this disease. Our review aims to summarize the
      literature on the subject, depicting possible mechanisms behind this IOP
      decrease, which type of patients are more likely to benefit from this surgery for
      IOP-lowering purposes and ultimately help optimizing disease management for the
      increasing number of patients with concomitant glaucoma and cataract.

PMID- 25765256
TI  - Influence of epoch length on measurement of dynamic functional connectivity in
      wakefulness and behavioural validation in sleep.
AB  - Conventional functional connectivity (FC) analysis of fMRI data derives a single
      measurement from the entire scan, generally several minutes in duration, which
      neglects the brain's dynamic behaviour and potentially loses important temporal
      information. Short-interval dynamic FC is an attractive proposition if
      methodological issues can be resolved and the approach validated. This was
      addressed in two ways; firstly we assessed FC of the posterior cingulate cortex
      (PCC) node of the default mode network (DMN) using differing temporal intervals
      (8s to 5min) in the waking-resting state. We found that 30-second intervals and
      longer produce spatially similar correlation topography compared to 15-minute
      static FC measurements, while providing increased temporal information about
      changes in FC that were consistent across interval lengths. Secondly, we used
      NREM sleep as a behavioural validation for the use of 30-second temporal
      intervals due to the known fMRI FC changes with sleep stage that have been
      observed in previous studies using intervals of several minutes. We found
      significant decreases in DMN FC with sleep depth which were most pronounced
      during stage N2 and N3. Additionally, both the proportion of time with strong PCC
      DMN connectivity and the variability in dynamic FC decreased with sleep. We
      therefore show that dynamic FC with epochs as short as tens of seconds is a
      viable method for characterising intrinsic brain activity. 

PMID- 25765258
TI  - Evaluation of Linear Alkylbenzene Sulfonate (LAS) behaviour in agricultural soil
      through laboratory continuous studies.
AB  - The behaviour of Linear Alkylbenzene Sulfonate (LAS) in agricultural soil is
      investigated in the laboratory using continuous-flow soil column studies in order
      to simultaneously analyze the three main underlying phenomena
      (adsorption/desorption, degradation and transport). The continuous-flow soil
      column experiments generated the breakthrough curves for each LAS homologue, C10,
      C11, C12 and C13, and by adding them up, for total LAS, from which the relevant
      retention, degradation and transport parameters could be estimated, after
      proposing adequate models. Several transport equations were considered, including
      the degradation of the sorbate in solution and its retention by soil, under
      equilibrium and non-equilibrium conditions between the sorbent and the sorbate.
      In general, the results obtained for the estimates of those parameters that were
      common to the various models studied (such as the isotherm slope, first order
      degradation rate coefficient and the hydrodynamic dispersion coefficient) were
      rather consistent, meaning that mass transfer limitations are not playing a major
      role in the experiments. These three parameters increase with the length of the
      LAS homologue chain. The study will provide the underlying conceptual framework
      and fundamental parameters to understand, simulate and predict the environmental
      behaviour of LAS compounds in agricultural soils. 

PMID- 25765257
TI  - Online fronto-cortical control of simple and attention-demanding locomotion in
      humans.
AB  - Knowledge of online functional brain mechanisms of locomotion is scarce due to
      technical limitations of traditional neuroimaging methods. Using functional Near
      Infrared Spectroscopy (fNIRS) we evaluated task-related changes in oxygenated
      hemoglobin levels (HbO2) in real-time over the pre-frontal-cortex (PFC) regions
      during simple (Normal Walk; NW) and attention-demanding (Walking While Talking;
      WWT) locomotion tasks in a large cohort of non-demented older adults. Results
      revealed that the assessment of task-related changes in HbO2 was internally
      consistent. Imposing greater demands on the attention system during locomotion
      resulted in robust bilateral PFC increases in HbO2 levels during WWT compared to
      NW and the cognitive interference tasks. Elevated PFC oxygenation levels were
      maintained throughout the course of WWT but not during the NW condition.
      Increased oxygenation levels in the PFC were related to greater stride length and
      better cognitive performance but not to faster gait velocity in WWT. These
      findings elucidate online brain mechanisms of locomotion, and confer significant
      implications for risk assessment and intervention for major mobility outcomes. 

PMID- 25765259
TI  - The Mossbauer study of atmospheric iron-containing aerosol in the coarse and
      PM2.5 fractions measured in rural site.
AB  - The size-resolved iron-containing atmospheric aerosol was measured by Mossbauer
      spectroscopy. The particulate matter (PM) was size-segregated into aerosol<2.5MUm
      in diameter (fine fraction, PM2.5) and aerosol>2.5 MUm (coarse fraction). The
      Mossbauer spectra at room temperature show components assigned to mono- and
      polymeric species which are products related to hydrolysis of ferric solutions in
      the atmosphere. In order to extract reliable information regarding the quadrupole
      splittings necessary for identification of iron-containing compounds, the
      histogram method was used for evaluation of the Mossbauer spectra. The value and
      distribution of quadrupole splitting (QS) parameters obtained by this method
      suggests that the ultra fine particles (<10 nm) identified as a ferrihydrite,
      hematite and goethite were observed in the spectra both in fine and coarse
      fraction of the collected aerosol. However, the content of the individual
      chemical components was different for each fraction. The least crystalline form
      of ferrihydrite (QS?0.85 mm) was observed in PM2.5 fraction more frequently than
      in the coarse fraction. The content of the ultra fine hematite particles which
      presence was confirmed in low temperature measurements was also larger in PM2.5
      fraction than in the coarse fraction. Superparamagnetic behavior of iron
      containing atmospheric aerosol was observed in low temperature Mossbauer spectra.

PMID- 25765260
TI  - Dehalogenation of persistent halogenated organic compounds: A review of
      computational studies and quantitative structure-property relationships.
AB  - Dehalogenation is one of the highly important degradation reactions for
      halogenated organic compounds (HOCs) in the environment, which is also being
      developed as a potential type of the remediation technologies. In combination
      with the experimental results, intensive efforts have recently been devoted to
      the development of efficient theoretical methodologies (e.g. multi-scale
      simulation) to investigate the mechanisms for dehalogenation of HOCs. This review
      summarizes the structural characteristics of neutral molecules, anionic species
      and excited states of HOCs as well as their adsorption behavior on the surface of
      graphene and the Fe cluster. It discusses the key physiochemical properties (e.g.
      frontier orbital energies and thermodynamic properties) calculated at various
      levels of theory (e.g. semiempirical, ab initio, density functional theory (DFT)
      and the periodic DFT) as well as their connections to the reactivity and reaction
      pathway for the dehalogenation. This paper also reviews the advances in the
      linear and nonlinear quantitative structure-property relationship models for the
      dehalogenation kinetics of HOCs and in the mathematical modeling of the
      dehalogenation processes. Furthermore, prospects of further expansion and
      exploration of the current research fields are described in this article. 

PMID- 25765261
TI  - An efficient laboratory workflow for environmental risk assessment of organic
      chemicals.
AB  - In this study, we demonstrate a fast and efficient workflow to investigate the
      transformation mechanism of organic chemicals and evaluate the toxicity of their
      transformation products (TPs) in laboratory scale. The transformation process of
      organic chemicals was first simulated by electrochemistry coupled online to mass
      spectrometry (EC-MS). The simulated reactions were scaled up in a batch EC
      reactor to receive larger amounts of a reaction mixture. The mixture sample was
      purified and concentrated by solid phase extraction (SPE) for the further
      ecotoxicological testing. The combined toxicity of the reaction mixture was
      evaluated in fish egg test (FET) (Danio rerio) compared to the parent compound.
      The workflow was verified with carbamazepine (CBZ). By using EC-MS seven primary
      TPs of CBZ were identified; the degradation mechanism was elucidated and
      confirmed by comparison to literature. The reaction mixture and one primary
      product (acridine) showed higher ecotoxicity in fish egg assay with 96 h EC50
      values of 1.6 and 1.0 mg L(-1) than CBZ with the value of 60.8 mg L(-1). The
      results highlight the importance of transformation mechanism study and
      toxicological effect evaluation for organic chemicals brought into the
      environment since transformation of them may increase the toxicity. The developed
      process contributes a fast and efficient laboratory method for the risk
      assessment of organic chemicals and their TPs.

PMID- 25765262
TI  - Photocatalytic degradation of the antiviral drug Tamiflu by UV-A/TiO2: Kinetics
      and mechanisms.
AB  - The photocatalytic degradation of the antiviral drug Tamiflu (oseltamivir
      phosphate, OP) by TiO2 - P25, ST-01 and ATO was investigated in aqueous solution
      under ultraviolet (UV-A) irradiation. The photocatalysis of OP is well described
      by pseudo-first-order kinetics with r2>98.0% for all cases. The kinetic constant
      of P25 with 80% anatase and 20% rutile (0.040 min(-1)) is 4 and 10 times higher
      than that of ATO and ST-01 with 100% purity of anatase, respectively. We examined
      the effects of the catalyst loading and initial OP concentration on the
      photodegradation of OP, and used potassium iodine, isopropanol, and calcium
      fluorine as radical quenchers to evaluate the contributions of the hydroxyl
      radical (OH) and photo hole (h+) in the photodegradation. Results confirmed that
      80% of the contribution came from the OH species. Although more than 95% of the
      OP (21 MUM) was removed after 80 min of UV-A irradiation with 20 and 100 mg L(-1)
      P25, the removal efficiencies of total organic carbon (TOC) were only 45.6% and
      67.0%, respectively, after 360 min UV-A irradiation. Based on an intermediate
      analysis by HPLC coupled with a triple quadrupole spectrometer and an ion trap
      mass spectrometer, typical intermediate species such as hydration derivatives,
      hydroxyl substitutes and keto-derivatives were identified and possible
      degradation pathways of OP by P25 were proposed.

PMID- 25765263
TI  - Sorption and competition of two persistent organic pesticides onto marine
      sediments: Relevance to their distribution in aquatic system.
AB  - Sorption is a key process in the distribution of substances between environmental
      compartments in marine ecosystems. Two persistent organic pesticides, also known
      as toxaphene congeners, namely B8-1413 (P26) and B9-1679 (P50), are of special
      interest because they are not detected in sediments while relatively concentrated
      in marine mammals. Sorption-desorption, entrapment and competition behaviors of
      these pesticides onto marine sediments were studied to explain their
      environmental distribution. Data obtained under marine experimental conditions
      were fitted to sorption models to evaluate sorption coefficients and to assess
      the degree of B8-1413/B9-1679 entrapment of the two toxaphene congeners in
      sediments. Carbon normalized sorption coefficients (Koc) of both congeners were
      similar under in cold (2 degrees C) marine (30 psu) conditions with high values
      ranging from 1.53*10(5) to 3.28*10(5) mL g(-1)indicative of a strong affinity to
      marine sediments However, the sorption-desorption investigations indicate that B8
      1413/B9-1679 were on average 2.5 times less entrapped in sediments compared to B7
      1450, a toxaphene congener known to accumulate predominantly in sediments. These
      results suggest that the low entrapment of B8-1413 and B9-1679 favor their
      availability and transfer to biological matrices.

PMID- 25765264
TI  - Iron in non-hydroxyl radical mediated photochemical processes for dye
      degradation: Catalyst or inhibitor?
AB  - The acetylacetone (AA) mediated photochemical process has been proven as an
      efficient approach for decoloration. For azo dyes, the UV/AA process was several
      to more than ten times more efficient than the UV/H2O2 process. Iron is one of
      the most common elements on the earth. It is well known that iron can improve the
      UV/H2O2 process through thermal Fenton and photo-Fenton reactions. What will be
      the role of iron in the UV/AA process? Could iron-AA complexes act as
      photocatalysts in environmental remediation? To answer these questions, the photo
      degradation of an azo dye, Acid Orange 7 (AO7), was conducted under the variant
      combinations of AA with iron species in both ionic (Fe2+, Fe3+) and complex
      (Fe(AA)3) forms. The pseudo-first-order decoloration rate constants of AO7 in
      these photochemical processes followed such an order:
      UV/Fe(II)/AA<UV/Fe(III)/AA<UV/Fe(AA)3<UV/AA. The results demonstrate that iron
      species, in either ionic or complex form, acts as an inhibitor rather than a
      catalyst in the UV/AA process. Based on spectroscopic analysis, the inner filter
      effect of iron and the competition between Fe(III) and AA for the complexation
      with AO7 were attributed to the inhibition effect of iron on the UV/AA process.
      The understanding of the role of iron provides insight into the practical
      application of the UV/AA process.

PMID- 25765266
TI  - High-contrast fluorescence imaging based on the polarization dependence of the
      fluorescence enhancement using an optical interference mirror slide.
AB  - High-contrast fluorescence imaging using an optical interference mirror (OIM)
      slide that enhances the fluorescence from a fluorophore located on top of the OIM
      surface is reported. To enhance the fluorescence and reduce the background light
      of the OIM, transverse-electric-polarized excitation light was used as incident
      light, and the transverse-magnetic-polarized fluorescence signal was detected. As
      a result, an approximate 100-fold improvement in the signal-to-noise ratio was
      achieved through a 13-fold enhancement of the fluorescence signal and an 8-fold
      reduction of the background light. 

PMID- 25765267
TI  - Screen printed paper-based diagnostic devices with polymeric inks.
AB  - A simple and low-cost fabrication method for paper-based diagnostic devices
      (PBDDs) is described in this study. Street-available polymer solutions were
      screen printed onto filter papers to create hydrophobic patterns for fluidic
      channels. In order to obtain fully functional hydrophobic patterns for fluids,
      the original polymer solutions were diluted with butyl acetate to yield a
      suitable viscosity range between 30-200 cP for complete patterning on paper.
      Typical pH and glucose tests with color indicators were performed on the screen
      printed PBDDs. Images of the PBDDs were analyzed by computers to obtain
      calibration curves for pH between 2 and 12 and glucose concentration ranging from
      10-1000 mmol dm(-3). Detection of formaldehyde in acetone was also carried out to
      show the possibility of using this PBBD for analytical detection with organic
      solvents. An exemplar PBDD with simultaneous pH and glucose detection was also
      used to demonstrate the feasibility of applying this technique for realistic
      diagnostic applications.

PMID- 25765268
TI  - Self-assembled nanowire arrays as three-dimensional nanopores for filtration of
      DNA molecules.
AB  - Molecular filtration and purification play important roles for biomolecule
      analysis. However, it is still necessary to improve efficiency and reduce the
      filtration time. Here, we show self-assembled nanowire arrays as three
      dimensional (3D) nanopores embedded in a microfluidic channel for ultrafast DNA
      filtration. The 3D nanopore structure was formed by a vapor-liquid-solid (VLS)
      nanowire growth technique, which allowed us to control pore size of the
      filtration material by varying the number of growth cycles. lambda DNA molecules
      (48.5 kbp) were filtrated from a mixture of T4 DNA (166 kbp) at the entrance of
      the 3D nanopore structure within 1 s under an applied electric field. Moreover,
      we observed single DNA molecule migration of T4 and lambda DNA molecules to
      clarify the filtration mechanism. The 3D nanopore structure has simplicity of
      fabrication, flexibility of pore size control and reusability for biomolecule
      filtration. Consequently it is an excellent material for biomolecular filtration.

PMID- 25765269
TI  - Label-free electrochemical detection of the human adenovirus 40/41 fiber gene.
AB  - A nanoporous silicon-based label-free DNA biosensor was fabricated to monitor
      rapidly enteric adenovirus types 40 and 41, a leading cause of viral
      gastroenteritis in children. Nanoporous silicon (NPS) was formed by an anodic
      etching process in a mixture solution containing hydrofluoric acid and ethanol.
      The polypyrrole (PPy) film was directly electropolymerized on The NPS substrate.
      Twenty-five base pairs of probe DNA (pDNA), derived from the fiber gene, was
      electrochemically doped on the PPy-coated NPS substrate. The conductivity change
      due to the immobilized pDNA and hybridized target DNA (tDNA) was expressed as an
      arbitrary factor, gamma, which is a normalized numerical term used for the
      selective quantification of the tDNA. gamma was inversely proportional to the
      concentration of complementary tDNA, but independent of the non-complementary
      tDNA. The sensitivity slope for detecting tDNAc was -1.54 MUM(-1), based on the
      factor gamma in the range of 0.4 to 1.0 MUM of tDNA. The surface roughness was
      characterized using atomic force microscopy. 

PMID- 25765270
TI  - Assessment of cadmium and lead adsorption in organic and conventional coffee.
AB  - Many metals are toxic in human organism, as is the case of cadmium and lead.
      Therefore, the metal levels in food need to be controlled. In coffee, metals may
      present risks when they are extracted from the powder to be consumed as beverage.
      A flow injection analysis (FIA) system is proposed, with atomic absorption
      detection, to metal adsorption studies in coffee powder. Kinetic study, best
      isotherms and time, and mass influences were determined. They allowed analyzing
      the high lead and cadmium adsorption percentage in organic and conventional
      ground coffee. Metal adsorption occurs in multilayers, following Freundlich's
      model, and the kinetic model obeyed is the pseudo-second order. The cadmium
      adsorption suffered higher temperature influence, while the lead retention
      suffered higher mass influence. This study indicates that the majority of these
      toxic agents will be retained in the powder and will not be consumed by man,
      avoiding possible deleterious effects. 

PMID- 25765271
TI  - Label-free detection of antigen protein using a metal mesh device surface
      modified by an antibody.
AB  - A biosensor for protein detection was developed using antibody-immobilized metal
      mesh devices. Antihemoglobin antibodies were covalently immobilized on a metal
      mesh device. Extraordinary transmission with a dipped structure was observed for
      a metal mesh device immobilized with antihemoglobin antibodies as well as for the
      original metal mesh device. Hemoglobin in the mixture solution containing albumin
      at a hundred-fold concentration was detectable using antihemoglobin-immobilized
      MMDs. The detectability using the antihemoglobin-immobilized metal mesh device
      was similar to that of a commercially-available kit for the qualitative
      determination of hemoglobin. 

PMID- 25765272
TI  - Fluorescent character of Cu(I/II) complexes with bisquinoline-based ligands and
      fluorometric detection of reductants.
AB  - The fluorescence ligands N,N'-bis(2-methylquinolyl)dimethylethylenediamine
      (BQDMEN) and N,N'-bis(2-methylquinolyl)dimethyl-1,3-propanediamine (BQDMPN) were
      synthesized. [Cu(II)(bqdmen)](2+) and [Cu(II)(bqdmpn)](2+) were prepared, and
      their reduction to [Cu(I)(bqdmen)](+) and [Cu(I)(bqdmpn)](+) was confirmed by the
      observed UV-Vis spectral change. Then, the fluorescence of
      [Cu(I/II)(bqdmen)](+/2+) and [Cu(I/II)(bqdmpn)](+/2+) in aqueous solution was
      characterized; [Cu(I)(bqdmen)](+) and [Cu(I)(bqdmpn)](+) were found to fluoresce
      in aqueous solution, whereas the fluorescence of [Cu(II)(bqdmen)](2+) and
      [Cu(II)(bqdmpn)](2+) was completely quenched. On the basis of these findings,
      fluorometric detection of reductants with a flow-injection system using a
      [Cu(II)(bqdmen)](2+) or [Cu(II)(bqdmpn)](2+) solution as a carrier was explored. 

PMID- 25765273
TI  - A tetraphenylethylene-based fluorescent chemosensor for Cu2+ in aqueous solution
      and its potential application to detect histidine.
AB  - A tetraphenylethylene-based compound with the property of aggregation-induced
      emission was designed and synthesized. It exhibited good sensitivity and
      selectivity to Cu(2+) over other metal ions (Zn(2+), Cd(2+), Ba(2+), Ni(2+),
      Mg(2+), Ca(2+), Co(2+), Fe(3+), Pb(2+), Mn(2+), Fe(2+), Ag(+), K(+), and Hg(2+))
      in an aqueous solution by the "turn-off" UV-vis absorbance and fluorescence
      signals. More interesting, with the subsequent addition of histidine rather than
      other amino acids such as proline, alanine, aspartic acid, lysine, arginine,
      leucine, glutamine or cysteine, the complex between the compound and Cu(2+) was
      disrupted, and the UV-vis absorbance and fluorescence signals were recovered,
      indicating that the complex from the compound and Cu(2+) could be used as a "turn
      on" fluorescent probe for histidine. 

PMID- 25765274
TI  - Continuous-flow size-based separation of microparticles by microchip
      electromagnetophoresis.
AB  - A novel microchip separation method for microparticles based on
      electromagnetophoresis was developed. In this method, a double Y-shape microchip
      with two inlets and two outlets was used for particle separation. Microparticles
      of two different sizes were suspended in an aqueous solution and introduced into
      the microchannel from one inlet with a stream of the aqueous solution without
      particles from another inlet by a hydrodynamic flow. Then, the particles with two
      different sizes were migrated orthogonal to the flow by elctromagnetophoresis and
      separated to different outlets based on the difference in their
      electromagnetophoric velocities, which depended on the size of particle. Using
      this method, at one outlet, 89% of 3 MUm polystyrene latex particles were
      isolated from a mixture of 3 and 10 MUm particles. By combining hydrodynamic
      focusing, both 3 and 10 MUm particles were recovered at the different outlets
      with 100% purity and recovery, respectively. Even the separation of 3 and 6 MUm
      particles was also achieved with about 98% recovery and purity. Moreover, yeast
      cells and polystyrene particles could be separated with high separation
      efficiency by this technique. 

PMID- 25765275
TI  - Rapid method for quantification of seven synthetic pigments in colored Chinese
      steamed buns using UFLC-MS/MS without SPE.
AB  - Synthetic pigments are still used instead of natural pigments in many foods and
      their residues in food could be an important risk to human health. A simple and
      rapid analytical method combining the low-cost extraction protocol with ultra
      fast liquid chromatography-tandem quadrupole mass spectrometry (UFLC-MS/MS) was
      developed for the simultaneous determination of seven synthetic pigments used in
      colored Chinese steamed buns. For the first time, ethanol/ammonia solution/water
      (7:2:1, v/v/v) was used as extraction solution for the synthetic pigments in
      colored Chinese steamed buns. The results showed that the property of the
      extraction solution used in this method was more effective than critic acid
      solution, which is used in the polyamide adsorption method. The limits of
      quantification for the seven synthetic pigments ranged from 0.15 to 0.50 MUg/kg.
      The present method was successfully applied to samples of colored Chinese steamed
      buns for food-safety risk monitoring in Zhejiang Province, China. The results
      found sunset yellow pigment in six out of 300 colored Chinese steamed buns (from
      0.50 to 32.6 MUg/kg). 

PMID- 25765277
TI  - Separation of boron from borated paraffin wax by pyrohydrolysis and alkali
      extraction methods and its determination using ion chromatography.
AB  - A method based on the pyrohydrolysis extraction of boron and its quantification
      with ion chromatography was proposed for paraffin waxes borated with H3BO3 and
      B4C. The optimum pyrohydrolysis conditions were identified. Wax samples were
      mixed with U3O8, which prevents the sample from flare up, and also accelerates
      the extraction of boron. Pyrohydrolysis was carried out with moist O2 at 950
      degrees C for 60 and 90 min for wax with H3BO3 and wax with B4C, respectively.
      Two simple methods of separation based on alkali extraction and melting wax in
      alkali were also developed exclusively for wax with H3BO3. In all the
      separations, the recovery of B was above 98%. During IC separation, B was
      separated as boron-mannitol anion complex. Linear calibration was obtained it
      between 0.1 and 50 ppm of B, and LOD was calculated as 5 ppb (S/N = 3). The
      reproducibility was better than 5% (RSD). 

PMID- 25765276
TI  - Countercurrent chromatographic separation of proteins using an eccentric coiled
      column with synchronous and nonsynchronous type-J planetary motions.
AB  - Protein separation was performed using the high-speed countercurrent
      chromatograph (HSCCC) at both synchronous and nonsynchronous type-J planetary
      motions. The partition efficiency was evaluated with two different column
      configurations, eccentric coil and toroidal coil, on the separation of a set of
      stable protein samples including cytochrome C, myoglobin and lysozyme with a
      polymer phase system composed of 12.5% (w/w) polyethylene glycol 1000 and 12.5%
      (w/w) dibasic potassium phosphate. Better peak resolution was obtained by the
      eccentric coil than by the toroidal coil using either lower or upper phase as the
      mobile phase. The peak resolution was further improved using the eccentric coil
      by the nonsynchronous type-J planetary motion with the combination of 1066 rpm of
      column rotation and 1000 rpm of revolution. 

PMID- 25765278
TI  - Selective detection toward quercetin and kaempferol on NH3-plasma treated carbon
      nanotubes modified glassy carbon electrode.
AB  - NH3-plasma treated multi-walled carbon nanotubes (pn-MWCNTs) were prepared based
      on the plasma technique and developed as sensing materials for detection of
      quercetin and kaempferol with the differential pulse voltammetry (DPV) and
      amperometric measurement. Such experimental parameters as pH values, accumulation
      potential and accumulation time were carefully investigated. The pn-MWCNTs
      modified electrode (pn-MWCNTs/GCE) was further explored for the analysis of
      quercetin and kaempferol in diluted blood serum and average recovery rates of
      96.91 and 100.5% were obtained, respectively. In addition, the interference and
      stability measurements were evaluated under the optimized experimental
      conditions. More importantly, selective detection toward quercetin and kaempferol
      was achieved, and the proposed electrochemical sensing strategy was available to
      distinguish substances with similar oxidation potential. 

PMID- 25765279
TI  - A comparative fluorescent beacon-based method for serum microRNA quantification.
AB  - Circulating serum microRNAs (miRNAs) are promising biomarkers for disease
      diagnosis. The quantification of the serum miRNA copy number is a challenge due
      to the presence of low levels in the serum. Here, we report on a direct
      measurement of the miRNA copy number from human serum using a locked nucleic acid
      (LNA) modified beacon probe with a single step using fluorescence spectroscopy
      and microscopy. We had used a minimum volume of 0.1 MUL healthy human serum and
      retinoblastoma serum to show the biological variation of the miRNA copy number. 

PMID- 25765281
TI  - Complete atomistic model of a bacterial cytoplasm for integrating physics,
      biochemistry, and systems biology.
AB  - A model for the cytoplasm of Mycoplasma genitalium is presented that integrates
      data from a variety of sources into a physically and biochemically consistent
      model. Based on gene annotations, core genes expected to be present in the
      cytoplasm were determined and a metabolic reaction network was reconstructed. The
      set of cytoplasmic genes and metabolites from the predicted reactions were
      assembled into a comprehensive atomistic model consisting of proteins with
      predicted structures, RNA, protein/RNA complexes, metabolites, ions, and solvent.
      The resulting model bridges between atomistic and cellular scales, between
      physical and biochemical aspects, and between structural and systems views of
      cellular systems and is meant as a starting point for a variety of simulation
      studies. 

PMID- 25765283
TI  - Polarized neutron reflectivity from monolayers of self-assembled magnetic
      nanoparticles.
AB  - We prepared monolayers of iron oxide nanoparticles via self-assembly on a bare
      silicon wafer and on a vanadium film sputter deposited onto a plane sapphire
      substrate. The magnetic configuration of nanoparticles in such a dense assembly
      was investigated by polarized neutron reflectivity. A theoretical model fit shows
      that the magnetic moments of nanoparticles form quasi domain-like configurations
      at remanence. This is attributed to the dipolar coupling amongst the
      nanoparticles. 

PMID- 25765282
TI  - Parent and public interest in whole-genome sequencing.
AB  - OBJECTIVE: The aim of this study was to assess the baseline interest of the
      public in whole-genome sequencing (WGS) for oneself, parents' interest in WGS for
      their youngest children, and factors associated with such interest. METHODS: A
      random sample of adults from a probability-based nationally representative online
      panel was surveyed. All participants were provided basic information about WGS
      and then asked about their interest in WGS for themselves. Those participants who
      were parents were additionally asked about their interest in WGS for their
      children. The order in which parents were asked about their interest in WGS for
      themselves and for their child was randomized. The relationship between
      parent/child characteristics and interest in WGS was examined. RESULTS: The
      overall response rate was 62% (55% among parents). 58.6% of the total population
      (parents and nonparents) was interested in WGS for themselves. Similarly, 61.8%
      of the parents were interested in WGS for themselves and 57.8% were interested in
      WGS for their youngest children. Of note, 84.7% of the parents showed an
      identical interest level in WGS for themselves and their youngest children.
      Mothers as a group and parents whose youngest children had >=2 health conditions
      had significantly more interest in WGS for themselves and their youngest
      children, while those with conservative political ideologies had considerably
      less. CONCLUSIONS: While US adults have varying interest levels in WGS, parents
      appear to have similar interests in genome testing for themselves and their
      youngest children. As WGS technology becomes available in the clinic and private
      market, clinicians should be prepared to discuss WGS risks and benefits with
      their patients.

PMID- 25765285
TI  - Low doses of mercuric chloride cause the main features of anti-nucleolar
      autoimmunity in female outbred CFW mice.
AB  - The growth of the influence of anthropogenic factors aimed on the improvement of
      human life has its side effect, for example, living organisms receive increasing
      exposure to toxic mercuric compounds. Experimental data show that mercury (Hg)
      salts are able to induce systemic autoimmunity in rodents. This Hg-induced
      autoimmune process (HgIA) is characterized by T cell-dependent polyclonal
      activation of B lymphocytes, increased level of serum immunoglobulin G1 (IgG1)
      and immunoglobulin E (IgE), production of antinucleolar autoantibodies (ANoA),
      and immune complex deposition in multiple organs. HgIA in mice is used as a model
      of human systemic autoimmune disorders. However, the dose of mercuric chloride
      (HgCl2) usually used in laboratory mice to induce HgIA is above the allowable
      limit for everyday levels of Hg exposure in humans. So, we decided to determine
      the lowest dose of HgCl2 that is able to trigger autoimmunity in outbred Carworth
      Farms Swiss Webster (CFW) mice not genetically prone to HgIA development. The
      lowest dose (50 ug/kg body weight (b.w.)/week) was chosen to match the World
      Health Organization provisional weekly tolerable intake of total Hg for humans.
      We also tested HgCl2 at 500 and 1500 ug/kg b.w./week (6.5- and 2-fold less than
      usually used for induction of HgIA in mice). We found that even the lowest dose
      of Hg resulted in a statistically significant increase in serum level of IgG1
      after 8 weeks of treatment. HgCl2 in doses 500 and 1500 ug/kg b.w./week resulted
      in a significant increase in serum level of IgG1 after 4 weeks of treatment,
      followed by ANoA production. Sera of HgCl2-treated mice stained the regions in
      which the major autoantigen in HgIA, fibrillarin, was revealed. These results
      suggest that low doses of Hg are able to induce the main features of HgIA in
      genetically heterozygous mice, and that humans chronically exposed to low doses
      of Hg may be at risk of autoimmunity induction regardless of their genetic
      background. 

PMID- 25765284
TI  - PKA-type I selective constrained peptide disruptors of AKAP complexes.
AB  - A-Kinase Anchoring Proteins (AKAPs) coordinate complex signaling events by
      serving as spatiotemporal modulators of cAMP-dependent protein kinase activity in
      cells. Although AKAPs organize a plethora of diverse pathways, their cellular
      roles are often elusive due to the dynamic nature of these signaling complexes.
      AKAPs can interact with the type I or type II PKA holoenzymes by virtue of high
      affinity interactions with the R-subunits. As a means to delineate AKAP-mediated
      PKA signaling in cells, we sought to develop isoform-selective disruptors of AKAP
      signaling. Here, we report the development of conformationally constrained
      peptides named RI-STapled Anchoring Disruptors (RI-STADs) that target the
      docking/dimerization domain of the type 1 regulatory subunit of PKA. These high
      affinity peptides are isoform-selective for the RI isoforms, can outcompete
      binding by the classical AKAP disruptor Ht31, and can selectively displace
      RIalpha, but not RIIalpha, from binding the dual-specific AKAP149 complex.
      Importantly, these peptides are cell-permeable and disrupt Type I PKA-mediated
      phosphorylation events in the context of live cells. Hence, RI-STAD peptides are
      versatile cellular tools to selectively probe anchored type I PKA signaling
      events. 

PMID- 25765286
TI  - Single nucleotide polymorphism detection using gold nanoprobes and bio
      microfluidic platform with embedded microlenses.
AB  - The use of microfluidics platforms combined with the optimal optical properties
      of gold nanoparticles has found plenty of application in molecular biosensing.
      This paper describes a bio-microfluidic platform coupled to a non-cross-linking
      colorimetric gold nanoprobe assay to detect a single nucleotide polymorphism
      associated with increased risk of obesity fat-mass and obesity-associated (FTO)
      rs9939609 (Carlos et al., 2014). The system enabled significant discrimination
      between positive and negative assays using a target DNA concentration of 5 ng/uL
      below the limit of detection of the conventionally used microplate reader (i.e.,
      15 ng/uL) with 10 times lower solution volume (i.e., 3 uL). A set of optimization
      of our previously reported bio-microfluidic platform (Bernacka-Wojcik et al.,
      2013) resulted in a 160% improvement of colorimetric analysis results.
      Incorporation of planar microlenses increased 6 times signal-to-loss ratio
      reaching the output optical fiber improving by 34% the colorimetric analysis of
      gold nanoparticles, while the implementation of an optoelectronic acquisition
      system yielded increased accuracy and reduced noise. The microfluidic chip was
      also integrated with a miniature fiber spectrometer to analyze the assays'
      colorimetric changes and also the LEDs transmission spectra when illuminating
      through various solutions. Furthermore, by coupling an optical microscope to a
      digital camera with a long exposure time (30 s), we could visualise the different
      scatter intensities of gold nanoparticles within channels following salt
      addition. These intensities correlate well to the expected difference in
      aggregation between FTO positive (none to small aggregates) and negative samples
      (large aggregates).

PMID- 25765287
TI  - Effects of Age and Estradiol on Gene Expression in the Rhesus Macaque
      Hypothalamus.
AB  - BACKGROUND: The hypothalamus plays a key role in mediating the effects of
      estrogen on many physiological functions, including reproduction, metabolism, and
      thermoregulation. We have previously observed marked estrogen-dependent gene
      expression changes within the hypothalamus of rhesus macaques during aging,
      especially in the KNDy neurons of the arcuate-median eminence (ARC-ME) that
      produce kisspeptin, neurokinin B, and dynorphin A. Little is known, however,
      about the mechanisms involved in mediating the feedback from estrogen onto these
      neurons. METHODS: We used quantitative real-time PCR to profile age- and estrogen
      dependent gene expression changes in the rhesus macaque hypothalamus. Our focus
      was on genes that encode steroid receptors (ESR1, ESR2, PGR, and AR) and on
      enzymes that contribute to the local synthesis of 17beta-estradiol (E2; STS,
      HSD3B1/2, HSD17B5, and CYP19A). In addition, we used RT(2) ProfilerTM PCR Arrays
      to profile a larger set of genes that are integral to hypothalamic function.
      RESULTS: KISS1, KISS1R, TAC3, and NPY2R mRNA levels increased in surgically
      menopausal (ovariectomized) old females relative to age-matched ovariectomized
      animals that received E2 hormone therapy. In contrast, PGR, HSD17B, GNRH2,
      SLC6A3, KISS1, TAC3, and NPY2R mRNA levels increased after E2 supplementation.
      CONCLUSION: The rhesus macaque ARC-ME expresses many genes that are responsive to
      changes in circulating estrogen levels, even during old age, and these may
      contribute to causing the normal and pathophysiological changes that occur during
      menopause.

PMID- 25765289
TI  - Retraction.

PMID- 25765288
TI  - Magic Power: changing gender dynamics and sex-enhancement practices among youths
      in Makassar, Indonesia.
AB  - This paper examines changing sexualities and gender relations as they are
      reflected in the use of sexual enhancement products by young women and men in the
      eastern Indonesian city of Makassar. To examine the relationships between the use
      of these products and socially sanctioned gender roles, their 'gender scripts'
      were studied--the assumptions embedded in the products' design and advertising.
      What kinds of femininity and masculinity are expressed through their use? It was
      found that the most popular products--'magic tissues' that promise to prolong
      erections and a 'neotraditional' vaginal wash that promises to cleanse, perfume,
      and tighten vaginas--espouse the dual purpose of promoting sexual pleasure and
      hygiene. While it was found that the images in advertising to reflect changing
      gender relations in the field site, this research also points to enduring gender
      scripts in Indonesian culture: men should be virile, women should be clean and
      attractive.

PMID- 25765291
TI  - Holes in teeth - Dental caries in Neolithic and Early Bronze Age populations in
      Central Germany.
AB  - This study provides diachronic insight into the epidemiology of carious defects
      in teeth of Neolithic and Early Bronze Age populations in Central Germany over a
      period of 4000 years. The data were retrieved from skeletal remains uncovered at
      21 sites throughout the Middle Elbe-Saale region (MES), comprising a total of 494
      individuals with preserved teeth. The data generated were examined for age- and
      sex-related differences in order to gain information about the dietary habits and
      socio-economic structures of the period with the goal of identifying potential
      diachronic changes. The results indicated that dietary habits changed over the
      course of the Neolithic period: the prevalence of caries significantly decreased
      between the Early and Late Neolithic. The adults from the Early Neolithic sample,
      particularly those from the LBK bore the highest rate of caries. This highlights
      the essential importance of cereals in the diet of the early farmers in the
      Middle Elbe-Saale region. As time went on, meat and dairy products became more
      and more important, which had a positive impact on dental health. The data also
      show sex-specific differences: women were more often affected by caries than men
      and female jaws also generally exhibited greater numbers of carious teeth than
      their male counterparts. Dental health is a reflection of both biological factors
      and of economic and sociocultural structures. 

PMID- 25765292
TI  - Sleep disturbance and neuropsychological function in young children with ADHD.
AB  - Sleep disturbance, common among children with ADHD, can contribute to cognitive
      and behavioral dysfunction. It is therefore challenging to determine whether
      neurobehavioral dysfunction should be attributed to ADHD symptoms, sleep
      disturbance, or both. The present study examined parent-reported sleep problems
      (Children's Sleep Habits Questionnaire) and their relationship to
      neuropsychological function in 64 children, aged 4-7 years, with and without
      ADHD. Compared to typically developing controls, children with ADHD were reported
      by parents to have significantly greater sleep disturbance--including sleep onset
      delay, sleep anxiety, night awakenings, and daytime sleepiness--(all p <= .01),
      and significantly poorer performance on tasks of attention, executive control,
      processing speed, and working memory (all p < .01). Within the ADHD group, total
      parent-reported sleep disturbance was significantly associated with deficits in
      attention and executive control skills (all p <= .01); however, significant group
      differences (relative to controls) on these measures remained (p < .01) even
      after controlling for total sleep disturbance. While sleep problems are common
      among young children with ADHD, these findings suggest that inattention and
      executive dysfunction appear to be attributable to symptoms of ADHD rather than
      to sleep disturbance. The relationships among sleep, ADHD symptoms, and
      neurobehavioral function in older children may show different patterns as a
      function of the chronicity of disordered sleep.

PMID- 25765293
TI  - A pharmacoeconomic analysis of phosphate binders cost-effectiveness in the
      RISCAVID study.
AB  - BACKGROUND: A pharmacoeconomic analysis of the RISCAVID database aimed at
      assessing the cost effectiveness of phosphate binders in preventing CV mortality
      and morbidity over 7 years was performed. METHODS: Morbid or fatal events
      occurring in 750 chronic HD patients were recorded. Statistical analysis
      evaluated the distribution of variables and the effect of sevelamer on survival.
      A cost-effectiveness evaluation was performed using a probabilistic model based
      on a Markov chain. RESULTS: Multivariate analysis showed that treatment with
      sevelamer was associated with a reduced stroke incidence by 52% (p = 0.04) and
      reduced levels of C-reactive protein (p < 0.01). Cost-effectiveness evaluation
      evidenced a 33% decrease in hospital-days for patients treated with sevelamer,
      with and without comorbidities compared to patients undergoing calcium binders
      treatment. CONCLUSION: Treatment with sevelamer was associated with a reduced
      risk of stroke in HD patients, with a clear saving on disease-related costs for
      the Italian National Healthcare System.

PMID- 25765294
TI  - Bimatoprost versus Mometasone Furoate in the Treatment of Scalp Alopecia Areata:
      A Pilot Study.
AB  - BACKGROUND: Alopecia areata (AA) is an immune-mediated disease that targets
      anagen hair follicles. Despite various therapeutic options, there is no cure for
      AA. Prostaglandin analogues have been recognized as being capable of inducing
      hypertrichosis. OBJECTIVE: To compare the efficacy and safety of bimatoprost to
      those of corticosteroid in the treatment of scalp AA. METHODS: Thirty adult
      patients with patchy AA (S1) were included. Two AA patches were randomly assigned
      to treatment either by mometasone furoate 0.1% cream once daily (area A) or
      bimatoprost 0.03% solution twice daily (area B) for 3 months. Patients were
      assessed using the Severity of Alopecia Tool (SALT) scoring system for hair re
      growth. RESULTS: All responding AA patches showed significant reduction in their
      SALT score after therapy. Area B demonstrated significantly better results
      regarding rapidity of response in weeks, percentage of hair re-growth and side
      effects compared to area A. CONCLUSION: Bimatoprost solution represents a
      therapeutic option for scalp AA.

PMID- 25765295
TI  - Botulinum toxin for the treatment of refractory erythema and flushing of rosacea.
AB  - BACKGROUND: Persistent erythema and severe rosacea flushing can cause significant
      physical discomfort and emotional stress to patients. Currently, no satisfactory
      treatments are available. METHODS: We report two cases of refractory flushing and
      erythema of rosacea that were successfully treated with intradermal botulinum
      toxin injections. RESULTS: Good cosmetic results were achieved for both patients.
      The side effects during and after treatment were mild pain and localized
      bruising; these symptoms resolved within several days without further treatment.
      CONCLUSION: Intradermal botulinum toxin injection may be an effective treatment
      for refractory erythema and rosacea flushing that deserves further study in a
      larger patient population.

PMID- 25765296
TI  - Detection of Small Changes in Psoriasis Intensity with PrecisePASI.
AB  - BACKGROUND: The Psoriasis Area and Severity Index (PASI) is the score of choice
      to grade psoriasis severity and detect clinical changes. Due to low resolution
      based on the calculation of the score by fixed area classes, PASI scores <10 have
      little value. METHODS: At 756 patient examinations, psoriasis activity was
      measured with both PASI and PrecisePASI. RESULTS: PrecisePASI has a linear
      increase while PASI has a staircase pattern. Both scores meet at the endpoint
      relevant values of body surface area (BSA) 10, 30, 50, 70 and 90%. PASI and
      PrecisePASI correlate significantly over the whole range of BSA. In the region of
      BSA <5%, PrecisePASI shows a significantly higher resolution (p < 0.0001).
      CONCLUSION: The calculation of PrecisePASI corrects the undesired inaccuracies of
      PASI in the lower BSA ranges and is a tool to use as an endpoint in trials aiming
      to detect differences in the lower ranges of BSA.

PMID- 25765297
TI  - GxxxG motifs hold the TIM23 complex together.
AB  - Approximately 99% of the mitochondrial proteome is nucleus-encoded, synthesized
      in the cytosol, and subsequently imported into and sorted to the correct
      compartment in the organelle. The translocase of the inner mitochondrial membrane
      23 (TIM23) complex is the major protein translocase of the inner membrane, and is
      responsible for translocation of proteins across the inner membrane and their
      insertion into the inner membrane. Tim23 is the central component of the complex
      that forms the import channel. A high-resolution structure of the import channel
      is still missing, and structural elements important for its function are unknown.
      In the present study, we analyzed the importance of the highly abundant GxxxG
      motifs in the transmembrane segments of Tim23 for the structural integrity of the
      TIM23 complex. Of 10 glycines present in the GxxxG motifs in the first, second
      and third transmembrane segments of Tim23, mutations of three of them in
      transmembrane segments 1 and 2 resulted in a lethal phenotype, and mutations of
      three others in a temperature-sensitive phenotype. The remaining four caused no
      obvious growth phenotype. Importantly, none of the mutations impaired the import
      and membrane integration of Tim23 precursor into mitochondria. However, the
      severity of growth impairment correlated with the destabilization of the TIM23
      complex. We conclude that the GxxxG motifs found in the first and second
      transmembrane segments of Tim23 are necessary for the structural integrity of the
      TIM23 complex. 

PMID- 25765298
TI  - Pathogenic Escherichia coli and lipopolysaccharide enhance the expression of IL
      8, CXCL5, and CXCL10 in canine endometrial stromal cells.
AB  - Chemokines play a central role in cellular communication in response to bacterial
      infection. However, the knowledge of the chemokine responses to bacterial
      infections in dogs remains limited. Uterine bacterial infection (pyometra) is one
      of the most common bacterial diseases in dogs and causes sepsis in most of the
      cases. We have shown previously that dogs with pyometra have higher messenger RNA
      (mRNA) levels of chemokines in uterus. To assess whether the stromal part of the
      endometrium expresses chemokines in response to bacterial infection, we cultured
      endometrial stromal cells isolated from healthy dogs and exposed them to either
      live pathogenic Escherichia coli, isolated from the uterus of a dog with
      pyometra, or lipopolysaccharide. Changes in the mRNA expression of ELR(+) CXC
      chemokines, IL-8, CXCL5, CXCL7, and ELR(-) CXC chemokine, CXCL10, were measured
      after 24 hours using quantitative real-time polymerase chain reaction. Levels of
      IL-8, CXCL5, and CXCL10 were upregulated in endometrial stromal cells exposed to
      E coli and lipopolysaccharide, whereas the level of CXCL7 was decreased or
      unaffected. In addition, levels of IL-8 and CXCL5, but not CXCL7 or CXCL10, were
      significantly higher in dogs with pyometra than those in healthy dogs. Our
      findings show that pathogenic uterine-derived E coli induces a CXC chemokine
      response both in cultured endometrial stromal cells within 24 hours and in
      pyometra-affected uteri from dogs. Stromal cells could therefore play an
      important role in early neutrophil and T cell recruitment to the site of
      inflammation during gram-negative bacterial infection of the uterus. Further
      studies are needed to clarify the role of chemokines in host response to
      bacterial infection in dogs and the possibility of using chemokines as diagnostic
      parameters for bacterial infection in this species.

PMID- 25765299
TI  - Inflammatory cytokines and acute-phase proteins concentrations in the peripheral
      blood and uterus of cows that developed endometritis during early postpartum.
AB  - The aim of the study was to evaluate the level of proinflammatory cytokines
      (tumor necrosis factor-alpha [TNF-alpha], interleukin-6 [IL-6]), anti
      inflammatory cytokine (interleukin-10 [IL-10]), and acute-phase proteins
      (haptoglobin [Hp] and serum amyloid A [SAA]) in serum and uterine washings in
      cows that developed endometritis during the early postpartum period. The study
      was carried out on 40 cows. The experimental group consisted of 20 cows with
      subclinical endometritis and the control group of 20 cows without endometritis.
      Analyses in both groups of cows were carried out at 5, 22, and 40 days postpartum
      (DPP). Experimental material consisted of the blood serum and uterine washings.
      The levels of the following cytokines: TNF-alpha, IL-6, IL-10 and acute-phase
      proteins: Hp and SAA were determined using ELISA. Our study reported that the
      levels of TNF-alpha, IL-6, IL-10, Hp, and SAA at 22 DPP were higher in cows with
      subclinical endometritis (P < 0.001). The levels of TNF-alpha (P = 0.01), IL-6
      and IL-10 (P = 0.001), and Hp (P < 0.001) at 40 DPP were higher in cows with
      subclinical endometritis compared to healthy cows. The level of IL-10 in uterine
      washings at 5 DPP was higher (P = 0.001), whereas of SAA was lower (P = 0.01) in
      cows with subclinical endometritis. At 22 DPP, the levels of IL-6, IL-10, and Hp
      were higher (P < 0.001) in cows with endometritis. At 40 DPP, the level of TNF
      alpha was lower, whereas these of IL-10 and Hp were elevated (P < 0.001) in cows
      with endometritis compared to healthy cows. The results indicate that the
      evaluation of the levels of cytokines and Hp in serum, but primarily in uterine
      washings, can be an important diagnostic indicator in cows that developed
      subclinical endometritis. High levels of IL-10 in cows with subclinical
      endometritis may contribute to the weakening of local resistance mechanisms of
      the uterus and lead to the persistence of the inflammation in the postpartum
      period. The present study also shows that the simultaneous examination of
      selected parameters of antagonistic interactions allows for better assessment of
      the current state of local immunity in the uterus.

PMID- 25765301
TI  - Association between Stressful Life Events and Cognitive Disorders in Central
      Africa: Results from the EPIDEMCA Program.
AB  - BACKGROUND: Stressful life events (SLEs) are considered potential risk factors
      for cognitive disorders. Our objective was to investigate the association between
      SLEs and cognitive disorders among the elderly people in Central Africa. METHOD:
      A population-based study was conducted in the Central African Republic (CAR) and
      the Republic of Congo (ROC). Participants aged >=65 were interviewed using the
      Community Screening Interview for Dementia. Those who performed poorly were
      clinically assessed by neurologists. DSM-IV and Petersen criteria were required
      for a diagnosis of dementia or mild cognitive impairment (MCI), respectively.
      SLEs were assessed through 18 questions about events that occurred during
      childhood, adulthood and late-life. Sociodemographic, vascular and psychological
      factors were also documented. Multivariate multinomial logistic regression models
      were used to estimate the associations. RESULTS: MCI was positively associated
      with: the total number of SLEs (OR = 1.1, 95% CI: 1.0-1.2), the number of SLEs
      from the age of 65 (OR = 1.2, 95% CI: 1.0-1.3), the number of SLEs before the age
      of 16 among non-depressive participants (OR = 1.6, 95% CI: 1.2-2.2) and with a
      serious illness in a child experienced when the participant was aged 65 or more
      (OR = 2.8, 95% CI: 1.6-4.6). No association with dementia was observed.
      CONCLUSION: SLEs were positively associated with MCI but not dementia. More
      comprehensive studies are needed to further investigate this relationship.

PMID- 25765300
TI  - Comprehensive analysis of CCCH-type zinc finger family genes facilitates
      functional gene discovery and reflects recent allopolyploidization event in
      tetraploid switchgrass.
AB  - BACKGROUND: In recent years, dozens of Arabidopsis and rice CCCH-type zinc finger
      genes have been functionally studied, many of which confer important traits, such
      as abiotic and biotic stress tolerance, delayed leaf senescence and improved
      plant architecture. Switchgrass (Panicum virgatum) is an important bioenergy
      crop. Identification of agronomically important genes and/or loci is an important
      step for switchgrass molecular breeding. Annotating switchgrass CCCH genes using
      translational genomics methods will help further the goal of understanding
      switchgrass genetics and creating improved varieties. RESULTS: Taking advantage
      of the publicly-available switchgrass genomic and transcriptomic databases, we
      carried out a comprehensive analysis of switchgrass CCCH genes (PvC3Hs). A total
      of 103 PvC3Hs were identified and divided into 21 clades according to
      phylogenetic analysis. Genes in the same clade shared similar gene structure and
      conserved motifs. Chromosomal location analysis showed that most of the
      duplicated PvC3H gene pairs are in homeologous chromosomes. Evolution analysis of
      19 selected PvC3H pairs showed that 42.1% of them were under diversifying
      selection. Expression atlas of the 103 PvC3Hs in 21 different organs, tissues and
      developmental stages revealed genes with higher expression levels in lignified
      cells, vascular cells, or reproductive tissues/organs, suggesting the potential
      function of these genes in development. We also found that eight PvC3Hs in Clade
      XIV were orthologous to ABA- or stress- responsive CCCH genes in Arabidopsis and
      rice with functions annotated. Promoter and qRT-PCR analyses of Clade-XIV PvC3Hs
      showed that these eight genes were all responsive to ABA and various stresses.
      CONCLUSIONS: Genome-wide analysis of PvC3Hs confirmed the recent
      allopolyploidization event of tetraploid switchgrass from two closely-related
      diploid progenitors. The short time window after the polyploidization event
      allowed the existence of a large number of PvC3H genes with a high positive
      selection pressure onto them. The homeologous pairs of PvC3Hs may contribute to
      the heterosis of switchgrass and its wide adaptation in different ecological
      niches. Phylogenetic and gene expression analyses provide informative clues for
      discovering PvC3H genes in some functional categories. Particularly, eight PvC3Hs
      in Clade-XIV were found involved in stress responses. This information provides a
      foundation for functional studies of these genes in the future.

PMID- 25765302
TI  - Cerebrospinal fluid concentrations of N-acetylcysteine after oral administration
      in Parkinson's disease.
AB  - INTRODUCTION: Depletion of neuronal glutathione may contribute to the
      pathogenesis of Parkinson's disease (PD). N-acetylcysteine (NAC) can restore
      neuronal glutathione levels, but it has not been established whether NAC can
      cross the blood-brain barrier in humans. METHODS: Twelve patients with PD were
      given oral NAC twice daily for 2 days. Three doses were compared: 7 mg/kg, 35
      mg/kg, and 70 mg/kg. NAC, cysteine, and glutathione were measured in the
      cerebrospinal fluid (CSF) at baseline and 90 min after the last dose. Cognitive
      and motor functions were assessed pre- and post-NAC administration using the
      Montreal Cognitive Assessment (MoCA) and the Unified Parkinson's Disease Rating
      Scale part III motor subscore (UPDRS-III). RESULTS: Oral NAC produced a dose
      dependent increase in CSF NAC concentrations (p < 0.001), with the highest dose
      producing a CSF concentration of 9.26 +/- 1.62 MUM. There were no significant
      adverse events. NAC had no acute effect on motor or cognitive function.
      CONCLUSION: Orally administered NAC produces biologically relevant CSF NAC
      concentrations at doses that are well tolerated. The findings support the
      feasibility of NAC as a potential disease-modifying therapy for PD.

PMID- 25765303
TI  - Structural analyses and yeast production of the beta-1,3-1,4-glucanase catalytic
      module encoded by the licB gene of Clostridium thermocellum.
AB  - A thermophilic glycoside hydrolase family 16 (GH16) beta-1,3-1,4-glucanase from
      Clostridium thermocellum (CtLic16A) holds great potentials in industrial
      applications due to its high specific activity and outstanding thermostability.
      In order to understand its molecular machinery, the crystal structure of CtLic16A
      was determined to 1.95A resolution. The enzyme folds into a classic GH16 beta
      jellyroll architecture which consists of two beta-sheets atop each other, with
      the substrate-binding cleft lying on the concave side of the inner beta-sheet.
      Two Bis-Tris propane molecules were found in the positive and negative substrate
      binding sites. Structural analysis suggests that the major differences between
      the CtLic16A and other GH16 beta-1,3-1,4-glucanase structures occur at the
      protein exterior. Furthermore, the high catalytic efficacy and thermal profile of
      the CtLic16A are preserved in the enzyme produced in Pichia pastoris, encouraging
      its further commercial applications. 

PMID- 25765304
TI  - A convenient test for lipase activity in aqueous-based solutions.
AB  - We proposed a convenient and accurate method for the measurement of lipase
      activity in a uniform aqueous-based substrate solution. In this work, lipase from
      Candida rugosa was used as the model lipase to test its catalytic ability toward
      p-nitrophenyl palmitate (p-NPP), which was suspended in a mixture of p-NPP
      ethanol solution and buffer. An ultraviolet-visible spectrophotometer was used to
      efficiently measure the liberated p-nitrophenol without extraction or
      centrifugation. Several factors that affected lipase activity were investigated,
      such as the ratio of p-NPP ethanol solution to buffer, the concentrations of p
      NPP and lipase, as well as the temperature, reaction time, pH and agitation rate.
      Additionally, enzyme catalytic parameters such as Km, Vm and "activation energy"
      were also assessed. We determined the optimal conditions for lipase in this
      homogeneous system and demonstrated lipase's catalytic performance in this
      condition followed Michealis-Menten kinetics. 

PMID- 25765305
TI  - Examining the freezing process of an intermediate bulk containing an industrially
      relevant protein.
AB  - Numerous biopharmaceuticals are produced in recombinant microorganisms in the
      controlled environment of a bioreactor, a process known as Upstream Process. To
      minimize product loss due to physico-chemical and enzymatic degradation, the
      Upstream Process should be directly followed by product purification, known as
      Downstream Process. However, the Downstream Process can be technologically
      complex and time-consuming which is why Upstream and Downstream Process usually
      have to be decoupled temporally and spatially. Consequently, the product obtained
      after the Upstream Process, known as intermediate bulk, has to be stored. In
      those circumstances, a freezing procedure is often performed to prevent product
      loss. However, the freezing process itself is inseparably linked to physico
      chemical changes of the intermediate bulk which may in turn damage the product.
      The present study analysed the behaviour of a Tris-buffered intermediate bulk
      containing a biopharmaceutically relevant protein during a bottle freezing
      process. Major damaging mechanisms, like the spatiotemporal redistribution of ion
      concentrations and pH, and their influence on product stability were
      investigated. Summarizing, we show the complex events which happen in an
      intermediate bulk during freezing and explain the different causes for product
      loss. 

PMID- 25765306
TI  - Regioselectivity-driven evolution of CYP102D1 for improved synthesis of 3'-ortho
      dihydroxyisoflavone.
AB  - Daidzein is a major component of isoflavones, and its hydroxylated forms are
      valuable phytochemicals with anti-cancer and anti-oxidant activity. Due to the
      limitations of chemical synthesis of these hydroxylated structures, alternative
      enzymatic synthesis has been attempted. Previously, several protein-engineering
      approaches using CYP102D1 were investigated; these produced mutants with daidzein
      hydroxylation activity and regioselectivity through rational design (F96V/M246I)
      and saturation mutagenesis (A273H/G274E/T277G). However, the generated mutants
      have low regioselectivity (F96V/M246I) or low hydroxylation activity
      (A273H/G274E/T277G). Here, we characterized mutants capable of catalyzing C3'
      specific daidzein hydroxylation with enhanced hydroxylation activity and
      regioselectivity. In order to obtain regioselectivity toward the daidzein C3'
      position, site-saturation mutagenesis on the substrate-binding region of CYP102D1
      F96V/M246I was investigated. A high-throughput screening assay was then
      performed, based on O-dealkylation activity against the daidzein analog substrate
      4'-O-methyl-daidzein. This resulted in a mutant with more than 23-fold improved
      hydroxylation activity (55.6+/-17.9MUM(-1)min(-1), or 48.4mg/L titer) and
      regioselectivity over the 3'/6-position that was increased by three-fold (from
      0.9 to 2.6) compared with the F96V/M246I template enzyme. Furthermore, we carried
      out docking simulation studies that could partially explain the effects of these
      mutations on C3'-specific hydroxylation activity. 

PMID- 25765307
TI  - The GH67 alpha-glucuronidase of Paenibacillus curdlanolyticus B-6 removes
      hexenuronic acid groups and facilitates biodegradation of the model
      xylooligosaccharide hexenuronosyl xylotriose.
AB  - 4-O-Methylglucuronic acid (MeGlcA) side groups attached to the xylan backbone
      through alpha-1,2 linkages are converted to hexenuronic acid (HexA) during
      alkaline pulping. alpha-Glucuronidase (EC 3.2.1.139) hydrolyzes 1,2-linked MeGlcA
      from xylooligosaccharides. To determine whether alpha-glucuronidase can also
      hydrolyze HexA-decorated xylooligosaccharides, a gene encoding alpha
      glucuronidase (AguA) was cloned from Paenibacillus curdlanolyticus B-6. The
      purified protein degraded hexenuronosyl xylotriose (DeltaX3), a model substrate
      prepared from kraft pulp. AguA released xylotriose and HexA from DeltaX3, but the
      Vmax and kcat values for DeltaX3 were lower than those for MeGlcA, indicating
      that HexA side groups may affect the hydrolytic activity. To explore the
      potential for biological bleaching, DeltaX3 degradation was performed using
      intracellular extract from P. curdlanolyticus B-6. The intracellular extract,
      with synergistic alpha-glucuronidase and beta-xylosidase activities, degraded
      DeltaX3 to xylose and HexA. These results indicate that alpha-glucuronidase can
      be used to remove HexA from DeltaX3 derived from pulp, reducing the need for
      chemical treatments in the pulping process. 

PMID- 25765308
TI  - Heterologous production of caffeic acid from tyrosine in Escherichia coli.
AB  - Caffeic acid is a plant secondary metabolite and its biological synthesis has
      attracted increased attention due to its beneficial effects on human health. In
      this study, Escherichia coli was engineered for the production of caffeic acid
      using tyrosine as the initial precursor of the pathway. The pathway design
      included tyrosine ammonia lyase (TAL) from Rhodotorula glutinis to convert
      tyrosine to p-coumaric acid and 4-coumarate 3-hydroxylase (C3H) from
      Saccharothrix espanaensis or cytochrome P450 CYP199A2 from Rhodopseudomonas
      palustris to convert p-coumaric acid to caffeic acid. The genes were codon
      optimized and different combinations of plasmids were used to improve the titer
      of caffeic acid. TAL was able to efficiently convert 3mM of tyrosine to p
      coumaric acid with the highest production obtained being 2.62mM (472mg/L).
      CYP199A2 exhibited higher catalytic activity towards p-coumaric acid than C3H.
      The highest caffeic acid production obtained using TAL and CYP199A2 and TAL and
      C3H was 1.56mM (280mg/L) and 1mM (180mg/L), respectively. This is the first study
      that shows caffeic acid production using CYP199A2 and tyrosine as the initial
      precursor. This study suggests the possibility of further producing more complex
      plant secondary metabolites like flavonoids and curcuminoids. 

PMID- 25765309
TI  - Second generation engineering of transketolase for polar aromatic aldehyde
      substrates.
AB  - Transketolase has significant industrial potential for the asymmetric synthesis
      of carboncarbon bonds with new chiral centres. Variants evolved on propanal were
      found previously with nascent activity on polar aromatic aldehydes 3
      formylbenzoic acid (3-FBA), 4-formylbenzoic acid (4-FBA), and 3
      hydroxybenzaldehyde (3-HBA), suggesting a potential novel route to analogues of
      chloramphenicol. Here we evolved improved transketolase activities towards
      aromatic aldehydes, by saturation mutagenesis of two active-site residues (R358
      and S385), predicted to interact with the aromatic substituents. S385 variants
      selectively controlled the aromatic substrate preference, with up to 13-fold
      enhanced activities, and KM values comparable to those of natural substrates with
      wild-type transketolase. S385E even completely removed the substrate inhibition
      for 3-FBA, observed in all previous variants. The mechanisms of catalytic
      improvement were both mutation type and substrate dependent. S385E improved 3-FBA
      activity via kcat, but reduced 4-FBA activity via KM. Conversely, S385Y/T
      improved 3-FBA activity via KM and 4-FBA activity via kcat. This suggested that
      both substrate proximity and active-site orientation are very sensitive to
      mutation. Comparison of all variant activities on each substrate indicated
      different binding modes for the three aromatic substrates, supported by
      computational docking. This highlights a potential divergence in the evolution of
      different substrate specificities, with implications for enzyme engineering. 

PMID- 25765310
TI  - Immobilization of lipases on hydrophobic supports involves the open form of the
      enzyme.
AB  - The lipases from Thermomyces lanuginosus and Pseudomonas cepacia have been
      immobilized on octyl and cyanogen bromide (CNBr) agarose beads. The
      immobilization on octyl-agarose is slowed with increasing ionic strength, while
      the immobilization on CNBr is not significantly affected by the ionic strength.
      The inhibition of the immobilized preparations with diethyl p
      nitrophenylphosphate (D-pNPP) was analyzed. The inhibition was more rapid using
      octyl-lipase preparations than using covalent preparations, and the covalent
      preparations were much more sensitive to the reaction medium. The addition of
      detergent increased the inhibition rate of the covalent preparation while an
      increase on the ionic strength produced a slowdown of the inhibition rate by D
      pNPP for both lipases. The effect of the medium on the activity versus fully
      soluble substrate (methyl mandelate) was in the same direction. The octyl
      preparations presented a slight decrease in activity when comparing the results
      using different concentrations of sodium phosphate buffer (between 0.025 and 1M),
      while the CNBr preparations suffered drastic drops in its activity at high ionic
      strength. The results confirm that the lipases immobilized on octyl agarose
      presented their open form stabilized while the covalent preparation maintains a
      closing/opening equilibrium that may be modulated by altering the medium. 

PMID- 25765311
TI  - Direct xylan conversion into glycolipid biosurfactants, mannosylerythritol
      lipids, by Pseudozyma antarctica PYCC 5048(T).
AB  - Mannosylerythritol lipids (MEL) are glycolipid biosurfactants, produced by
      Pseudozyma spp., with increasing commercial interest. While MEL can be produced
      from d-glucose and d-xylose, the direct conversion of the respective
      lignocellulosic polysaccharides, cellulose and xylan, was not reported yet. The
      ability of Pseudozyma antarctica PYCC 5048(T) and Pseudozyma aphidis PYCC 5535(T)
      to use cellulose (Avicel((r))) and xylan (beechwood) as carbon and energy source
      has been assessed along with their capacity of producing cellulolytic and
      hemicellulolytic enzymes, toward a consolidated bioprocess (CBP) for MEL
      production. The yeasts assessed were neither able to grow in medium containing
      Avicel((r)) nor produce cellulolytic enzymes under the conditions tested. On
      contrary, both yeasts were able to efficiently grow in xylan, but MEL production
      was only detected in P. antarctica PYCC 5048(T) cultures. MEL titers reached
      1.3g/l after 10 days in batch cultures with 40g/l xylan, and 2.0g/l in fed-batch
      cultures with xylan feeding (additional 40g/l) at day 4. High levels of xylanase
      activities were detected in xylan cultures, reaching 47-62U/ml (31-32U/mg) at 50
      degrees C, and still exhibiting more than 10U/ml under physiological temperature
      (28 degrees C). Total beta-xylosidase activities, displayed mainly as wall
      bounded and extracellular activity, accounted for 0.154 and 0.176U/ml in P.
      antarctica PYCC 5048(T) and P. aphidis PYCC 5535(T) cultures, respectively. The
      present results demonstrate the potential of Pseudozyma spp. for using directly a
      fraction of lignocellulosic biomass, xylan, and combining in the same bioprocess
      the production of xylanolytic enzymes with MEL production. 

PMID- 25765312
TI  - Codon optimization, promoter and expression system selection that achieved high
      level production of Yarrowia lipolytica lipase in Pichia pastoris.
AB  - Lipase (EC 3.1.1.3) stands amongst the most important and promising biocatalysts
      for industrial applications. In this study, in order to realize a high-level
      expression of the Yarrowia lipolytica lipase gene in Pichia pastoris, we
      optimized the codon of LIP2 by de novo gene design and synthesis, which
      significantly improved the lipase expression when compared to the native lip2
      gene. We also comparatively analyzed the effects of the promoter types (PAOX1 and
      PFLD1) and the Pichia expression systems, including the newly developed
      PichiaPink system, on lipase production and obtained the optimal recombinants.
      Bench-top scale fermentation studies indicated that the recombinant carrying the
      codon-optimized lipase gene syn-lip under the control of promoter PAOX1 has a
      significantly higher lipase production capacity in the fermenter than other types
      of recombinants. After undergoing methanol inducible expression for 96h, the wet
      cell weight of Pichia, the lipase activity and the protein content in the
      fermentation broth reached their highest values of 262g/L, 38,500U/mL and
      2.82g/L, respectively. This study has not only greatly facilitated the
      bioapplication of lipase in industrial fields but the strategies utilized, such
      as de novo gene design and synthesis, the comparative analysis among promoters
      and different generations of Pichia expression systems will also be useful as
      references for future work in this field. 

PMID- 25765313
TI  - SOAX: a software for quantification of 3D biopolymer networks.
AB  - Filamentous biopolymer networks in cells and tissues are routinely imaged by
      confocal microscopy. Image analysis methods enable quantitative study of the
      properties of these curvilinear networks. However, software tools to quantify the
      geometry and topology of these often dense 3D networks and to localize network
      junctions are scarce. To fill this gap, we developed a new software tool called
      "SOAX", which can accurately extract the centerlines of 3D biopolymer networks
      and identify network junctions using Stretching Open Active Contours (SOACs). It
      provides an open-source, user-friendly platform for network centerline
      extraction, 2D/3D visualization, manual editing and quantitative analysis. We
      propose a method to quantify the performance of SOAX, which helps determine the
      optimal extraction parameter values. We quantify several different types of
      biopolymer networks to demonstrate SOAX's potential to help answer key questions
      in cell biology and biophysics from a quantitative viewpoint. 

PMID- 25765314
TI  - Effects of Individual Differences and Situational Features on Age Differences in
      Mindless Reading.
AB  - OBJECTIVE: Mindless reading occurs when an individual shifts their attention away
      from the text and toward other off-task thoughts. This study examined whether
      previously reported age-related declines in mindless reading episodes are due
      primarily to (a) situational features related to the text itself (e.g., text
      genre or interest in the text) and/or (b) individual differences in cognitive
      ability. METHOD: Participants read 2 texts written in different genres but about
      the same topic. During reading, they were randomly probed to indicate whether
      they were on-task or mind-wandering. They also indicated their perceptions
      regarding the interest and difficulty of the text, and completed a battery of
      cognitive ability measures. RESULTS: The results showed that (a) text genre may
      engender some age differences in mindless reading and (b) greater age and
      perceived interest in the text were each uniquely predictive of reduced mindless
      reading for both text genres. Individual differences in cognitive abilities
      (e.g., working memory, vocabulary) did not account for additional significant
      variance in mindless reading after interest and age were taken into account.
      DISCUSSION: Our findings are discussed in terms of implications for age
      differences in lapses of attention during reading and predictors of mind
      wandering generally.

PMID- 25765315
TI  - Marital Quality and Cognitive Limitations in Late Life.
AB  - OBJECTIVES: Identifying factors associated with cognitive limitations among older
      adults has become a major public health objective. Given the importance of
      marital relationships for older adults' health, this study examines the
      association between marital quality and change in cognitive limitations in late
      life, directionality of the relationship between marital quality and cognitive
      limitations, and potential gender differences in these associations. METHOD:
      Latent growth curve models were used to estimate the association of marital
      quality with change in cognitive limitations among older adults and the direction
      of the association between marital quality and cognitive limitations using 4
      waves of the Americans' Changing Lives survey (N = 841). RESULTS: Results
      indicate that more frequent negative (but not positive) marital experiences are
      associated with a slower increase in cognitive limitations over time, and the
      direction of this association does not operate in the reverse (i.e., cognitive
      limitations did not lead to change in marital quality over time). The association
      between negative marital experiences and cognitive limitations is similar for men
      and women. DISCUSSION: The discussion highlights possible explanations for the
      apparent protective effect of negative marital experiences for older adults'
      cognitive health over time, regardless of gender.

PMID- 25765316
TI  - The differential expression of BmGlcNAcase2 in strains of Bombyx mori
      (Lepidoptera: Bombycidae) with different susceptibility to Bombyx mori
      (Lepidoptera: Bombycidae) nucleopolyhedrovirus infection.
AB  - GlcNAcase is a glycosyl hydrolase located in the lysosomes of numerous organisms.
      Levels of the protein, beta-N-acetylglucosaminidase 2 (GlcNAcase2), which is a
      member of the GlcNAcase family, are different in two strains of the silkworm
      Bombyx mori that have different resistance to Bombyx mori nucleopolyhedroviruses
      (BmNPVs). We identified six single-nucleotide differences in the GlcNAcase2
      coding sequence between the 306 and NB strains. Five are silent changes, but one
      is a nonsynonymous mutation. Reverse transcription-polymerase chain reaction
      analysis showed that GlcNAcase2 mRNA levels in the NB strain were nearly 2.57
      times higher compared with those in the 306 strain. In addition, GlcNAcase2
      enzyme activity was much higher in the NB strain compared with that in the 306
      strain. Together, these results indicate that GlcNAcase2 may be involved in
      variable BmNPV resistance in B. mori.

PMID- 25765317
TI  - First report of Oryctes rhinoceros nudivirus (Coleoptera: Scarabaeidae) causing
      severe disease in Allomyrina dichotoma in Korea.
AB  - Oryctes rhinoceros nudivirus (OrNV) has been known to cause severe disease in
      coconut palm rhinoceros beetle, Oryctes rhinoceros, in Southeastern Asia and is
      used as a biological control to reduce the pest population. Here, we report for
      the first time that the OrNV may have landed on Korea and may be the major
      pathogen for diseased larvae of Korean horn beetle, Allomyrina dichotoma. After
      peroral inoculation, over 60% of infected larvae perished in 6 wk. This viral
      disease spreads very fast in several locations throughout Korea. This threat not
      only makes economic loss of local farms rearing A. dichotoma larvae but also may
      disturb the ecosystem by transmitting to wild A. dichotoma. 

PMID- 25765318
TI  - Genomic analysis of LPS-stimulated myeloid cells identifies a common pro
      inflammatory response but divergent IL-10 anti-inflammatory responses.
AB  - Inflammation is an essential physiological response to infection and injury that
      must be kept within strict bounds. The IL-10/STAT3 anti-inflammatory response
      (AIR) is indispensable for controlling the extent of inflammation, although the
      complete mechanisms downstream of STAT3 have not yet been elucidated. The AIR is
      widely known to extend to other myeloid cells, but it has best been characterized
      in macrophages. Here we set out to characterize the LPS-mediated pro-inflammatory
      response and the AIR across a range of myeloid cells. We found that whereas the
      LPS-induced pro-inflammatory response is broadly similar among macrophages,
      dendritic cells, neutrophils, mast cells and eosinophils, the AIR is drastically
      different across all myeloid cell types that respond to IL-10 (all bar
      eosinophils). We propose a model whereby the IL-10/STAT3 AIR works by selectively
      inhibiting specific pathways in distinct cell types: in macrophages the AIR most
      likely works through the inhibition of NF-kappaB target genes; in DCs and mast
      cells through indirect IRF disruption; and in neutrophils through IRF disruption
      and possibly also indirect NF-kappaB inhibition. In summary, no conserved IL
      10/STAT3 AIR effectors were identified; instead a cell type-specific model of the
      AIR is proposed. 

PMID- 25765320
TI  - Oscillatory mechanisms of feedforward and feedback visual processing.
AB  - Two recent monkey studies demonstrate that feedforward processing in the visual
      system is reflected by activity in the 40-90Hz gamma band, whereas feedback is
      reflected by activity in the 5-18Hz alpha and beta band. These findings can be
      applied to interpret human electrophysiological activity in complex visual tasks.

PMID- 25765319
TI  - Epigenetic mechanisms of chronic pain.
AB  - Neuropathic and inflammatory pain promote a large number of persisting
      adaptations at the cellular and molecular level, allowing even transient tissue
      or nerve damage to elicit changes in cells that contribute to the development of
      chronic pain and associated symptoms. There is evidence that injury-induced
      changes in chromatin structure drive stable changes in gene expression and neural
      function, which may cause several symptoms, including allodynia, hyperalgesia,
      anxiety, and depression. Recent findings on epigenetic changes in the spinal cord
      and brain during chronic pain may guide fundamental advances in new treatments.
      Here, we provide a brief overview of epigenetic regulation in the nervous system
      and then discuss the still-limited literature that directly implicates epigenetic
      modifications in chronic pain syndromes. 

PMID- 25765321
TI  - RNA-binding proteins in neurodegeneration: Seq and you shall receive.
AB  - As critical players in gene regulation, RNA binding proteins (RBPs) are taking
      center stage in our understanding of cellular function and disease. In our era of
      bench-top sequencers and unprecedented computational power, biological questions
      can be addressed in a systematic, genome-wide manner. Development of high
      throughput sequencing (Seq) methodologies provides unparalleled potential to
      discover new mechanisms of disease-associated perturbations of RNA homeostasis.
      Complementary to candidate single-gene studies, these innovative technologies may
      elicit the discovery of unexpected mechanisms, and enable us to determine the
      widespread influence of the multifunctional RBPs on their targets. Given that the
      disruption of RNA processing is increasingly implicated in neurological diseases,
      these approaches will continue to provide insights into the roles of RBPs in
      disease pathogenesis. 

PMID- 25765322
TI  - Acting without seeing: eye movements reveal visual processing without awareness.
AB  - Visual perception and eye movements are considered to be tightly linked. Diverse
      fields, ranging from developmental psychology to computer science, utilize eye
      tracking to measure visual perception. However, this prevailing view has been
      challenged by recent behavioral studies. Here, we review converging evidence
      revealing dissociations between the contents of perceptual awareness and
      different types of eye movement. Such dissociations reveal situations in which
      eye movements are sensitive to particular visual features that fail to modulate
      perceptual reports. We also discuss neurophysiological, neuroimaging, and
      clinical studies supporting the role of subcortical pathways for visual
      processing without awareness. Our review links awareness to perceptual-eye
      movement dissociations and furthers our understanding of the brain pathways
      underlying vision and movement with and without awareness. 

PMID- 25765324
TI  - Serum anti-60S ribosomal protein L29 antibody as a novel prognostic marker for
      unresectable pancreatic cancer.
AB  - BACKGROUND/AIMS: Recently, we found the presence of anti-60S ribosomal protein
      L29 antibody (anti-RPL29) in human sera, inhibiting the proliferation of
      pancreatic cancer cells in vitro. We aimed to estimate the association of serum
      anti- RPL29 levels with clinical features in patients affected with unresectable
      pancreatic cancer. METHODS: We retrospectively reviewed 105 patients with
      unresectable pancreatic cancer. Serum anti-RPL29 levels were measured by the
      indirect enzyme-linked immunosorbent assay. The cut-off was represented by the
      95th percentile in 62 healthy volunteers. RESULTS: Median survival time (MST) was
      11.1 months in 49 patients showing serum anti-RPL29 level >cut-off and 7.4 months
      in 56 patients showing serum anti-RPL29 level <= cutoff. In locally advanced
      disease, MST was 17.9 months in 22 patients showing serum anti-RPL29 level >cut
      off and 10.0 months in 19 patients showing serum anti-RPL29 level <= cutoff. In
      metastatic disease, MST was 8.7 months in 27 patients showing serum anti-RPL29
      level >cut-off and 5.9 months in 37 patients showing serum anti-RPL29 level <=
      cut-off. In the multivariate Cox proportional hazard model, serum anti- RPL29
      level >cut-off, abdominal or back pain, performance status, and metastatic
      disease were identified as independent prognostic factors. CONCLUSION: Serum anti
      RPL29 levels may be a novel candidate for a prognostic marker for unresectable
      pancreatic cancer.

PMID- 25765325
TI  - Practical tips for implementing bundled payments in your practice: Hoag
      Orthopedic Institute - a joint venture model for value-based care delivery.

PMID- 25765323
TI  - Towards the automatic classification of neurons.
AB  - The classification of neurons into types has been much debated since the
      inception of modern neuroscience. Recent experimental advances are accelerating
      the pace of data collection. The resulting growth of information about
      morphological, physiological, and molecular properties encourages efforts to
      automate neuronal classification by powerful machine learning techniques. We
      review state-of-the-art analysis approaches and the availability of suitable data
      and resources, highlighting prominent challenges and opportunities. The effective
      solution of the neuronal classification problem will require continuous
      development of computational methods, high-throughput data production, and
      systematic metadata organization to enable cross-laboratory integration. 

PMID- 25765327
TI  - The integrative role of the pedunculopontine nucleus in human gait.
AB  - The brainstem pedunculopontine nucleus has a likely, although unclear, role in
      gait control, and is a potential deep brain stimulation target for treating
      resistant gait disorders. These disorders are a major therapeutic challenge for
      the ageing population, especially in Parkinson's disease where gait and balance
      disorders can become resistant to both dopaminergic medication and subthalamic
      nucleus stimulation. Here, we present electrophysiological evidence that the
      pedunculopontine and subthalamic nuclei are involved in distinct aspects of gait
      using a locomotor imagery task in 14 patients with Parkinson's disease undergoing
      surgery for the implantation of pedunculopontine or subthalamic nuclei deep brain
      stimulation electrodes. We performed electrophysiological recordings in two
      phases, once during surgery, and again several days after surgery in a subset of
      patients. The majority of pedunculopontine nucleus neurons (57%) recorded
      intrasurgically exhibited changes in activity related to different task
      components, with 29% modulated during visual stimulation, 41% modulated during
      voluntary hand movement, and 49% modulated during imaginary gait.
      Pedunculopontine nucleus local field potentials recorded post-surgically were
      modulated in the beta and gamma bands during visual and motor events, and we
      observed alpha and beta band synchronization that was sustained for the duration
      of imaginary gait and spatially localized within the pedunculopontine nucleus. In
      contrast, significantly fewer subthalamic nucleus neurons (27%) recorded
      intrasurgically were modulated during the locomotor imagery, with most increasing
      or decreasing activity phasically during the hand movement that initiated or
      terminated imaginary gait. Our data support the hypothesis that the
      pedunculopontine nucleus influences gait control in manners extending beyond
      simply driving pattern generation. In contrast, the subthalamic nucleus seems to
      control movement execution that is not likely to be gait-specific. These data
      highlight the crucial role of these two nuclei in motor control and shed light on
      the complex functions of the lateral mesencephalus in humans. 

PMID- 25765326
TI  - Somatosensory cortex functional connectivity abnormalities in autism show
      opposite trends, depending on direction and spatial scale.
AB  - Functional connectivity is abnormal in autism, but the nature of these
      abnormalities remains elusive. Different studies, mostly using functional
      magnetic resonance imaging, have found increased, decreased, or even mixed
      pattern functional connectivity abnormalities in autism, but no unifying
      framework has emerged to date. We measured functional connectivity in individuals
      with autism and in controls using magnetoencephalography, which allowed us to
      resolve both the directionality (feedforward versus feedback) and spatial scale
      (local or long-range) of functional connectivity. Specifically, we measured the
      cortical response and functional connectivity during a passive 25-Hz vibrotactile
      stimulation in the somatosensory cortex of 20 typically developing individuals
      and 15 individuals with autism, all males and right-handed, aged 8-18, and the mu
      rhythm during resting state in a subset of these participants (12 per group, same
      age range). Two major significant group differences emerged in the response to
      the vibrotactile stimulus. First, the 50-Hz phase locking component of the
      cortical response, generated locally in the primary (S1) and secondary (S2)
      somatosensory cortex, was reduced in the autism group (P < 0.003, corrected).
      Second, feedforward functional connectivity between S1 and S2 was increased in
      the autism group (P < 0.004, corrected). During resting state, there was no group
      difference in the mu-alpha rhythm. In contrast, the mu-beta rhythm, which has
      been associated with feedback connectivity, was significantly reduced in the
      autism group (P < 0.04, corrected). Furthermore, the strength of the mu-beta was
      correlated to the relative strength of 50 Hz component of the response to the
      vibrotactile stimulus (r = 0.78, P < 0.00005), indicating a shared aetiology for
      these seemingly unrelated abnormalities. These magnetoencephalography-derived
      measures were correlated with two different behavioural sensory processing scores
      (P < 0.01 and P < 0.02 for the autism group, P < 0.01 and P < 0.0001 for the
      typical group), with autism severity (P < 0.03), and with diagnosis (89%
      accuracy). A biophysically realistic computational model using data driven
      feedforward and feedback parameters replicated the magnetoencephalography data
      faithfully. The direct observation of both abnormally increased and abnormally
      decreased functional connectivity in autism occurring simultaneously in different
      functional connectivity streams, offers a potential unifying framework for the
      unexplained discrepancies in current findings. Given that cortical feedback,
      whether local or long-range, is intrinsically non-linear, while cortical
      feedforward is generally linear relative to the stimulus, the present results
      suggest decreased non-linearity alongside an increased veridical component of the
      cortical response in autism. 

PMID- 25765328
TI  - Astrocyte uncoupling as a cause of human temporal lobe epilepsy.
AB  - Glial cells are now recognized as active communication partners in the central
      nervous system, and this new perspective has rekindled the question of their role
      in pathology. In the present study we analysed functional properties of
      astrocytes in hippocampal specimens from patients with mesial temporal lobe
      epilepsy without (n = 44) and with sclerosis (n = 75) combining patch clamp
      recording, K(+) concentration analysis, electroencephalography/video-monitoring,
      and fate mapping analysis. We found that the hippocampus of patients with mesial
      temporal lobe epilepsy with sclerosis is completely devoid of bona fide
      astrocytes and gap junction coupling, whereas coupled astrocytes were abundantly
      present in non-sclerotic specimens. To decide whether these glial changes
      represent cause or effect of mesial temporal lobe epilepsy with sclerosis, we
      developed a mouse model that reproduced key features of human mesial temporal
      lobe epilepsy with sclerosis. In this model, uncoupling impaired K(+) buffering
      and temporally preceded apoptotic neuronal death and the generation of
      spontaneous seizures. Uncoupling was induced through intraperitoneal injection of
      lipopolysaccharide, prevented in Toll-like receptor4 knockout mice and reproduced
      in situ through acute cytokine or lipopolysaccharide incubation. Fate mapping
      confirmed that in the course of mesial temporal lobe epilepsy with sclerosis,
      astrocytes acquire an atypical functional phenotype and lose coupling. These data
      suggest that astrocyte dysfunction might be a prime cause of mesial temporal lobe
      epilepsy with sclerosis and identify novel targets for anti-epileptogenic
      therapeutic intervention. 

PMID- 25765330
TI  - Transfusion medicine in Australia.

PMID- 25765329
TI  - Transcriptome sequencing and analysis of the entomopathogenic fungus Hirsutella
      sinensis isolated from Ophiocordyceps sinensis.
AB  - BACKGROUND: Ophiocordyceps sinensis, a worm and fungus combined mixture which
      Hirsutella sinensis is parasitic on the caterpillar body, has been used as a
      traditional medicine or healthy food in China for thousands of years. H. sinensis
      is reported as the only correct anamorph of O. sinensis and its main active
      ingredients are similar to the natural O. sinensis. RESULTS: H. sinensis L0106,
      asexual strain of O. sinensis, was isolated and identified in this study. Three
      transcriptomes of H. sinensis at different cultivation periods (growth period 3d,
      pre-stable period 6d and stable period 9d) were sequenced for the first time by
      RNA-Seq method, and 25,511 unigenes (3d), 25,214 unigenes (6d) and 16,245
      unigenes (9d) were assembled and obtained, respectively. These unigenes of the
      three samples were further assembled into 20,822 unigenes (All), and 62.3 percent
      of unigenes (All) could be annotated based on protein databases. Subsequently,
      the genes and enzymes involved in the biosynthesis of the active ingredients
      according to the sequencing and annotation results were predicted. Based on the
      predictions, we further investigated the interaction of different pathway
      networks and the corresponding enzymes. Furthermore, the differentially expressed
      genes (DEGs) of H. sinensis grown during different developmental stages (3d-VS
      6d, 3d-VS-9d and 6d-VS-9d) were globally detected and analyzed based on the data
      from RNA-Seq, and 764 DEGs between 3d and 6d, 1,869 DEGs between 3d and 9d, and
      770 DEGs between 6d and 9d were found, respectively. CONCLUSIONS: This work
      presented here would aid in understanding and carrying out future studies on the
      genetic basis of H. sinensis and contribute to the further artificial production
      and application of this organism. This study provided a substantial contribution
      and basis to further characterize the gene expression profiles of H. sinensis in
      the metabolic pathways of active ingredients.

PMID- 25765332
TI  - Bumetanide for treatment of seizures in neonates.

PMID- 25765334
TI  - Facile synthesis of spirooxindole-pyrazolines and spirobenzofuranone-pyrazolines
      and their fungicidal activity.
AB  - Novel spirooxindole-pyrazolines and spirobenzofuranone-pyrazolines have been
      synthesized in good to excellent yields via the annulation reactions of the
      corresponding 3-alkylideneoxindoles and 3-alkylidenebenzofuranones with Huisgen
      zwitterions. The preliminary bioassay demonstrated that some of the
      spiropyrazolines possess good in vitro fungicidal activity against several crop
      fungi at a concentration of 50 MUg mL(-1). 

PMID- 25765335
TI  - Age Differences in Trade-off Decisions: Different Strategies but Similar
      Outcomes.
AB  - The primary purpose of this study was to examine age differences in processing
      strategies of emotionally difficult trade-off decisions. In addition, the study
      tested the relevant contributions of the cognitive and emotional mechanisms to
      age differences in processing strategies. Altogether, 40 younger adults and 40
      older adults were randomly assigned to either a high or low emotionally difficult
      condition of a car-purchasing decision task. MouselabWEB software was used to
      trace participants' processing strategies. Results showed that older adults were
      more likely to use attribute-based processing strategies, whereas younger adults
      were more likely to use alternative-based processing strategies in the high
      emotion condition. In the low-emotion condition, on the other hand, both younger
      and older adults preferred to use alternative-based processing strategies.
      Furthermore, the results suggested that the cognitive measure (i.e., digit symbol
      coding) was not correlated with the age effects on processing strategies. 

PMID- 25765333
TI  - Bumetanide for the treatment of seizures in newborn babies with hypoxic ischaemic
      encephalopathy (NEMO): an open-label, dose finding, and feasibility phase 1/2
      trial.
AB  - BACKGROUND: Preclinical data suggest that the loop-diuretic bumetanide might be
      an effective treatment for neonatal seizures. We aimed to assess dose and
      feasibility of intravenous bumetanide as an add-on to phenobarbital for treatment
      of neonatal seizures. METHODS: In this open-label, dose finding, and feasibility
      phase 1/2 trial, we recruited full-term infants younger than 48 h who had hypoxic
      ischaemic encephalopathy and electrographic seizures not responding to a loading
      dose of phenobarbital from eight neonatal intensive care units across Europe.
      Newborn babies were allocated to receive an additional dose of phenobarbital and
      one of four bumetanide dose levels by use of a bivariate Bayesian sequential dose
      escalation design to assess safety and efficacy. We assessed adverse events,
      pharmacokinetics, and seizure burden during 48 h continuous electroencephalogram
      (EEG) monitoring. The primary efficacy endpoint was a reduction in electrographic
      seizure burden of more than 80% without the need for rescue antiepileptic drugs
      in more than 50% of infants. The trial is registered with ClinicalTrials.gov,
      number NCT01434225. FINDINGS: Between Sept 1, 2011, and Sept 28, 2013, we
      screened 30 infants who had electrographic seizures due to hypoxic ischaemic
      encephalopathy. 14 of these infants (10 boys) were included in the study (dose
      allocation: 0.05 mg/kg, n=4; 0.1 mg/kg, n=3; 0.2 mg/kg, n=6; 0.3 mg/kg, n=1). All
      babies received at least one dose of bumetanide with the second dose of
      phenobarbital; three were withdrawn for reasons unrelated to bumetanide, and one
      because of dehydration. All but one infant also received aminoglycosides. Five
      infants met EEG criteria for seizure reduction (one on 0.05 mg/kg, one on 0.1
      mg/kg and three on 0.2 mg/kg), and only two did not need rescue antiepileptic
      drugs (ie, met rescue criteria; one on 0.05 mg/kg and one on 0.3 mg/kg). We
      recorded no short-term dose-limiting toxic effects, but three of 11 surviving
      infants had hearing impairment confirmed on auditory testing between 17 and 108
      days of age. The most common non-serious adverse reactions were moderate
      dehydration in one, mild hypotension in seven, and mild to moderate electrolyte
      disturbances in 12 infants. The trial was stopped early because of serious
      adverse reactions and limited evidence for seizure reduction. INTERPRETATION: Our
      findings suggest that bumetanide as an add-on to phenobarbital does not improve
      seizure control in newborn infants who have hypoxic ischaemic encephalopathy and
      might increase the risk of hearing loss, highlighting the risks associated with
      the off-label use of drugs in newborn infants before safety assessment in
      controlled trials. FUNDING: European Community's Seventh Framework Programme.

PMID- 25765336
TI  - Evaluation of the nutrition screening tool for childhood cancer (SCAN).
AB  - BACKGROUND & AIMS: Malnutrition is a serious concern for children with cancer and
      nutrition screening may offer a simple alternative to nutrition assessment for
      identifying children with cancer who are at risk of malnutrition. The present
      paper aimed to evaluate the nutrition screening tool for childhood cancer (SCAN).
      METHODS: SCAN was developed after an extensive review of currently available
      tools and published screening recommendation, consideration of pediatric oncology
      nutrition guidelines, piloting questions, and consulting with members of
      International Pediatric Oncology Nutrition Group. In Study 1, the accuracy and
      validity of SCAN against pediatric subjective global nutrition assessment
      (pediatric SGNA) was determined. In Study 2, subjects were classified as 'at risk
      of malnutrition' and 'not at risk of malnutrition' according to SCAN and measures
      of height, weight, body mass index (BMI) and body composition were compared
      between the groups. RESULTS: The validation of SCAN against pediatric SGNA showed
      SCAN had 'excellent' accuracy (0.90, 95% CI 0.78-1.00; p < 0.001), 100%
      sensitivity, 39% specificity, 56% positive predictive value and 100% negative
      predictive value. When subjects in Study 2 were classified into 'at risk of
      malnutrition' and 'not at risk of malnutrition' according to SCAN, the 'at risk
      of malnutrition' group had significantly lower values for weight Z score (p =
      0.001), BMI Z score (p = 0.001) and fat mass index (FMI) (p = 0.04), than the
      'not at risk of malnutrition' group. CONCLUSIONS: This study shows that SCAN is a
      simple, quick and valid tool which can be used to identify children with cancer
      who are at risk of malnutrition.

PMID- 25765337
TI  - Transcriptome analysis highlights preformed defences and signalling pathways
      controlled by the prAe1 quantitative trait locus (QTL), conferring partial
      resistance to Aphanomyces euteiches in Medicago truncatula.
AB  - To gain an insight into the molecular mechanisms of quantitative disease
      resistance in Medicago truncatula to the root-infecting oomycete Aphanomyces
      euteiches, we selected two near-isogenic lines (NILs), NR and NS, partially
      resistant and susceptible, respectively, differing in the allelic state of the
      quantitative resistance locus (QRL) prAe1 (partially resistant to A. euteiches
      1). Complementary molecular and cytological phenotyping methods showed that prAe1
      alone confers quantitative resistance to A. euteiches. Root and stem tissues were
      colonized in NS plants and 80% of NS plants died by 21 days post-inoculation
      (dpi). In contrast, A. euteiches mycelium was restricted to the root cortex and
      the spread of symptoms was arrested in aerial parts of NR plants. A transcriptome
      analysis performed at 0, 1 and 6 dpi identified 1198 differentially expressed
      genes (DEGs) between NR and NS lines. More than 87% of the DEGs were
      significantly more expressed in NR. The highest number of DEGs was found in
      control conditions, with 723 genes over-expressed in NR versus 85 in NS. Genes
      belonging to secondary metabolism, pathogenesis-related (PR) proteins and kinases
      were significantly enriched. The significant role of the flavonoid pathway in
      resistance was corroborated by the detection of larger amounts of flavonoids in
      NR roots and the inhibition of A. euteiches zoospore germination by 2'-O-methyl
      isoliquiritigenin, a compound synthesized by enzymes specifically induced in NR.
      Our study revealed that prAe1-dependent resistance relies mainly on the
      constitutive expression of defence-related pathways and signalling elements,
      which can be re-amplified in later time points of the infection.

PMID- 25765338
TI  - Protective effect of antioxidants on DNA damage in leukocytes from X-linked
      adrenoleukodystrophy patients.
AB  - Toxic metabolites accumulation and oxidative stress have been associated to the
      pathophysiology of X-linked adrenoleukodystrophy (X-ALD), an inborn error of
      peroxisome metabolism. Parameters of oxidative damage to proteins and lipids in X
      ALD patients were already described in literature; however, DNA injuries were not
      studied yet. Considering that, the aims were to investigate DNA damage by comet
      assay in heterozygotes and symptomatic X-ALD patients, to look for associations
      between DNA damage and lipid peroxidation as measured by urinary 15-F2t
      isoprostane; and to evaluate the in vitro effect of N-acetyl-l-cysteine (NAC),
      trolox (TRO) and rosuvastatin (RSV) on DNA damage in leukocytes from symptomatic
      patients. Symptomatic patients presented higher DNA damage levels than those
      found in heterozygotes and controls; heterozygotes and controls showed similar
      results. In order to investigate the in vitro antioxidant effect on DNA damage,
      whole blood cells from symptomatic patients were incubated with NAC (1 and
      2.5mM), TRO (25 and 75 MUM) and RSV (0.5, 2 and 5 MUM) before DNA damage
      analysis. NAC, TRO and RSV, at all tested concentrations, were all capable to
      reduce DNA damage in symptomatic X-ALD patients until control levels. Finally,
      DNA damage correlated with urinary isoprostanes and plasmatic levels of TBA-RS
      and DCFH-DA, allowing to hypothesize that DNA damage might be induced by lipid
      peroxidation in symptomatic patients. The present work yields experimental
      evidence that NAC, TRO and RSV reduce the in vitro DNA injury in symptomatic X
      ALD patients, what may suggest that the administration of these antioxidants
      might be considered as an adjuvant therapy for X-ALD.

PMID- 25765339
TI  - Mechanistic aspects of the gas-phase coupling of thioanisole and chlorobenzene to
      dibenzothiophene catalyzed by atomic Ho(+).
AB  - Mechanistic aspects of the novel gas-phase generation of dibenzothiophene via
      coupling of thioanisole and chlorobenzene, employing atomic Ho(+) as a catalyst,
      have been investigated using Fourier-transform ion cyclotron resonance mass
      spectrometry in conjunction with density functional theory (DFT) calculations. 

PMID- 25765340
TI  - DNA-templated in situ growth of silver nanoparticles on mesoporous silica
      nanospheres for smart intracellular GSH-controlled release.
AB  - In this work, we propose a method for constructing silver nanoparticles (AgNPs)
      on mesoporous silica nanospheres (MSNs) by a DNA-templated process. By in situ
      formation, the gatekeeper can be easily modulated to meet different degrees of
      glutathione (GSH) stimuli for location-specific drug release. 

PMID- 25765341
TI  - Influence of hybrid nano-filler on the crystallization behaviour and interfacial
      interaction in polyamide 6 based hybrid nano-composites.
AB  - Expanded graphite (EG) and multiwalled carbon nanotubes (MWNTs) based hybrid nano
      composites were prepared with polyamide 6 (PA6) matrix via melt-mixing technique
      using a conical twin-screw micro-compounder. A novel organic modifier (lithium
      salt of 6-aminohexanoic acid; Li-AHA) was employed to modify MWNTs, which was
      utilized to intercalate Li-AHA modified MWNTs into the partially exfoliated EG
      gallery. Morphological investigation showed the intercalation of Li-AHA modified
      MWNTs into a partially exfoliated EG gallery in an EG/MWNTs-m2h hybrid, whereas
      the unmodified EG/MWNTs-h hybrid mixture exhibited a separate identity in the
      mixture. Improved interaction via melt-interfacial reaction between the acid end
      group of PA6 and the amine functionality of Li-AHA in the EG/MWNTs-m2h hybrid
      filler was confirmed by Fourier transform infrared spectroscopic analysis. The
      extent of melt-interfacial reaction was increased as a function of Li-AHA
      concentration in the filler. Wide angle X-ray diffraction analysis showed the
      existence of the alpha-crystalline phase of PA6. The incorporation of MWNTs, EG
      and EG/MWNTs hybrid in the PA6 matrix has favoured an alpha-crystalline structure
      of the PA6 phase. Crystallization studies have indicated a significant increase
      in the bulk crystallization temperature of the PA6 phase in the presence of
      MWNTs, EG and the EG/MWNTs hybrid filler. Moreover, the formation of PA6 'trans
      crystalline lamellae' on the MWNTs surface was facilitated in the case of
      composites with MWNTs and the EG/MWNTs hybrid filler. An attempt has been made to
      investigate the role of the EG/MWNTs hybrid filler in influencing the
      crystallization behaviour of the PA6 phase in the hybrid nano-composites. 

PMID- 25765342
TI  - Detection of blaIMP4 and blaNDM1 harboring Klebsiella pneumoniae isolates in a
      university hospital in Malaysia.
AB  - Background : Antibiotic resistance among Enterobacteriaceae posts a great
      challenge to the health care service. The emergence of carbapenem-resistant
      Klebsiella pneumoniae (CRKP) is attracting significant attention due to its rapid
      and global dissemination. The infection is associated with significant morbidity
      and mortality, thus creating challenges for infection control and managing teams
      to curb the infection. In Southeast Asia, there have been limited reports and
      subsequent research regarding CRKP infections. Thus, the study was conducted to
      characterize CRKP that has been isolated in our setting. Methods : A total of 321
      K. pneumoniae were included in the study. Each isolate went through an
      identification process using an automated identification system. Phenotypic
      characterization was determined using disk diffusion, modified Hodge test,
      Epsilometer test, and inhibitor combined disk test. Further detection of
      carbapenemase genes was carried out using polymerase chain reaction and confirmed
      by gene sequence analysis. Results : All together, 13 isolates (4.05%) were CRKP
      and the majority of them were resistant to tested antibiotics except colistin and
      tigercycline. Among seven different carbapenemase genes studied (blaKPC, bla IMP,
      bla SME, bla NDM, bla IMI, bla VIM, and bla OXA), only two, bla IMP4 (1.87%) and
      bla NDM1 (2.18%), were detected in our setting. Conclusion : Evidence suggests
      that the prevalence of CRKP in our setting is low, and knowledge of Carbapenem
      resistant Enterobacteriaceae and CRKP has improved and become available among
      clinicians. 

PMID- 25765343
TI  - De novo assembly and transcriptome analysis of Atlantic salmon
      macrophage/dendritic-like TO cells following type I IFN treatment and Salmonid
      alphavirus subtype-3 infection.
AB  - BACKGROUND: Interferons (IFN) are cytokines secreted by vertebrate cells involved
      in activation of signaling pathways that direct the synthesis of antiviral genes.
      To gain a global understanding of antiviral genes induced by type I IFNs in
      salmonids, we used RNA-seq to characterize the transcriptomic changes induced by
      type I IFN treatment and salmon alphavirus subtype 3 (SAV-3) infection in TO
      cells, a macrophage/dendritic like cell-line derived from Atlantic salmon (Salmo
      salar L) head kidney leukocytes. RESULTS: More than 23 million reads generated by
      RNA-seq were de novo assembled into 58098 unigenes used to generate a total of
      3149 and 23289 differentially expressed genes (DEGs) from TO-cells exposed to
      type I IFN treatment and SAV-3 infection, respectively. Although the DEGs were
      classified into genes associated with biological processes, cellular components
      and molecular function based on gene ontology classification, transcriptomic
      changes reported here show upregulation of genes belonging to the canonical type
      I IFN signaling pathways together with a broad spectrum of antiviral genes that
      block virus replication in host cells. In addition, the transcriptome shows a
      profile of genes associated with apoptosis as well as genes that activate
      adaptive immunity. Further, our findings show that the profile of genes expressed
      by TO-cells is comparable to orthologous genes expressed by mammalian macrophages
      and dendritic cells in response to type I IFNs. Twenty DEGs randomly selected for
      qRT-PCR confirmed the validity of the transcriptomic changes detected by RNA-seq
      by showing that the genes upregulated by RNA-seq were also upregulated by qRT-PCR
      and that genes downregulated by RNA-seq were also downregulated by qRT-PCR.
      CONCLUSIONS: The de novo assembled transcriptome presented here provides a global
      description of genes induced by type I IFNs in TO-cells that could serve as a
      repository for future studies in fish cells. Transcriptome analysis shows that a
      large proportion of IFN genes expressed in this study are comparable to IFNs
      genes expressed in mammalia. In addition, the study shows that SAV-3 is a potent
      inducer of type I IFNs and that the responses it induces in TO-cells could serve
      as a model for studying IFN responses in salmonids.

PMID- 25765345
TI  - MUGBAS: a species free gene-based programme suite for post-GWAS analysis.
AB  - Genome Wide Association Studies between molecular markers and phenotypes are now
      routinely run in model and non-model species. However, tools to estimate the
      probability of association of functional units (e.g. genes) containing multiple
      markers are not developed for species other than humans. Here we introduce MUGBAS
      (MUlti species Gene-Based Association Suite), software that estimates the P-value
      of a gene using information on annotation, single marker GWA results and
      genotype. The software is species and annotation independent, fast, highly
      parallelized and ready for high-density marker studies. AVAILABILITY AND
      IMPLEMENTATION: https://bitbucket.org/capemaster/mugbas

PMID- 25765344
TI  - Estimating tissue iron burden: current status and future prospects.
AB  - Iron overload is becoming an increasing problem as haemoglobinopathy patients
      gain greater access to good medical care and as therapies for myelodysplastic
      syndromes improve. Therapeutic options for iron chelation therapy have increased
      and many patients now receive combination therapies. However, optimal utilization
      of iron chelation therapy requires knowledge not only of the total body iron
      burden but the relative iron distribution among the different organs. The
      physiological basis for extrahepatic iron deposition is presented in order to
      help identify patients at highest risk for cardiac and endocrine complications.
      This manuscript reviews the current state of the art for monitoring global iron
      overload status as well as its compartmentalization. Plasma markers, computerized
      tomography, liver biopsy, magnetic susceptibility devices and magnetic resonance
      imaging (MRI) techniques are all discussed but MRI has come to dominate clinical
      practice. The potential impact of recent pancreatic and pituitary MRI studies on
      clinical practice are discussed as well as other works-in-progress. Clinical
      protocols are derived from experience in haemoglobinopathies but may provide
      useful guiding principles for other iron overload disorders, such as
      myelodysplastic syndromes. 

PMID- 25765346
TI  - Structure-PPi: a module for the annotation of cancer-related single-nucleotide
      variants at protein-protein interfaces.
AB  - MOTIVATION: The interpretation of cancer-related single-nucleotide variants
      (SNVs) considering the protein features they affect, such as known functional
      sites, protein-protein interfaces, or relation with already annotated mutations,
      might complement the annotation of genetic variants in the analysis of NGS data.
      Current tools that annotate mutations fall short on several aspects, including
      the ability to use protein structure information or the interpretation of
      mutations in protein complexes. RESULTS: We present the Structure-PPi system for
      the comprehensive analysis of coding SNVs based on 3D protein structures of
      protein complexes. The 3D repository used, Interactome3D, includes experimental
      and modeled structures for proteins and protein-protein complexes. Structure-PPi
      annotates SNVs with features extracted from UniProt, InterPro, APPRIS, dbNSFP and
      COSMIC databases. We illustrate the usefulness of Structure-PPi with the
      interpretation of 1 027 122 non-synonymous SNVs from COSMIC and the 1000G Project
      that provides a collection of ~172 700 SNVs mapped onto the protein 3D structure
      of 8726 human proteins (43.2% of the 20 214 SwissProt-curated proteins in
      UniProtKB release 2014_06) and protein-protein interfaces with potential
      functional implications. AVAILABILITY AND IMPLEMENTATION: Structure-PPi, along
      with a user manual and examples, isavailable at
      http://structureppi.bioinfo.cnio.es/Structure, the code for local installations
      at https://github.com/Rbbt-Workflows

PMID- 25765347
TI  - ChIPseeker: an R/Bioconductor package for ChIP peak annotation, comparison and
      visualization.
AB  - ChIPseeker is an R package for annotating ChIP-seq data analysis. It supports
      annotating ChIP peaks and provides functions to visualize ChIP peaks coverage
      over chromosomes and profiles of peaks binding to TSS regions. Comparison of ChIP
      peak profiles and annotation are also supported. Moreover, it supports evaluating
      significant overlap among ChIP-seq datasets. Currently, ChIPseeker contains 15
      000 bed file information from GEO database. These datasets can be downloaded and
      compare with user's own data to explore significant overlap datasets for
      inferring co-regulation or transcription factor complex for further
      investigation. AVAILABILITY AND IMPLEMENTATION: ChIPseeker is released under
      Artistic-2.0 License. The source code and documents are freely available through
      Bioconductor
      (http://www.bioconductor.org/packages/release/bioc/html/ChIPseeker.html).

PMID- 25765348
TI  - A Single-Centre, Randomized, Double-Blind, Placebo-Controlled Clinical Trial to
      Investigate the Efficacy and Safety of Minoxidil Topical Foam in Frontotemporal
      and Vertex Androgenetic Alopecia in Men.
AB  - BACKGROUND: 5% minoxidil formulations twice daily are effective in treating
      vertex male androgenetic alopecia (AGA); however, efficacy and safety data in
      frontotemporal regions are lacking. OBJECTIVES: To assess the efficacy of 5%
      minoxidil topical foam (5% MTF) in the frontotemporal region of male AGA patients
      after 24 weeks of treatment compared to placebo treatment and to the vertex
      region. METHODS: Seventy males with moderate AGA applied 5% MTF or placebo foam
      (plaTF) twice daily for 24 weeks in frontotemporal and vertex regions. Target
      area non-vellus hair count (TAHC) was the primary end point. RESULTS:
      Frontotemporal and vertex TAHC and target area cumulative non-vellus hair width
      (TAHW) showed similar responses to 5% MTF with significant increases up to week
      16 compared to baseline (p < 0.001). After 24 weeks of treatment, frontotemporal
      TAHW increased significantly in the 5% MTF group compared to the plaTF group (p =
      0.017), while TAHC showed a similar non-significant increase from baseline in
      both regions. At 24 weeks, 5% MTF users rated a significant improvement in scalp
      coverage for the frontotemporal (p = 0.016) and vertex areas (p = 0.027).
      CONCLUSIONS: 5% MTF twice a day promotes hair density and width in both
      frontotemporal and vertex regions in men with moderate stages of AGA. (c) 2015 S.
      Karger AG, Basel.

PMID- 25765349
TI  - The role of answering behaviours on weight misreporting.
AB  - BACKGROUND: Biases in self-reported weight are very common among young adults and
      adults. Although social norms are the most commonly accepted explanation for
      these misreports, corresponding evidence is scarce and conflict-ridden. An
      alternative explanation for biases in weight self-reports comes from answering
      behaviours; non-random rounding, formally an answering behaviour, has been found
      to play a significant role in several studies of weight misreporting. However,
      the presumably rich role of answering behaviours has seldom been explored. This
      study brings a second answering behaviour into the analysis: inconsistency.
      METHODS: An inconsistency index was computed as an individual-level score from
      several questions across waves in the National Health and Nutrition Examination
      Survey. By regression analysis (N=3480 men and 1856 women) the simultaneous role
      of inconsistency and of non-random rounding on weight misreporting was explored.
      RESULTS: Inconsistency was found to be associated with higher self-reported
      weights. Inconsistent individuals provided significantly different misreports,
      with women under-reporting 0.23[kg] (0.01-0.45) less and men over-reporting
      0.42[kg] (0.02-0.82) more than their consistent counterparts. Inconsistency was
      found to play a simultaneous and substantially larger role than non-random
      rounding. This result was clearer among men than it was among women. DISCUSSION:
      Although social norms are usually thought to be the central explanation of weight
      biased misreports, there are other factors, such as answering behaviours, that
      might play a more influential role.

PMID- 25765350
TI  - Guillain-Barre syndrome (demyelinating) six weeks after bariatric surgery: A case
      report and literature review.
AB  - Obesity is a major health problem worldwide. Bariatric surgery has been
      increasingly used to manage obesity. Many acute as well as chronic neurological
      complications have been reported after bariatric surgery including Guillain-Barre
      syndrome (GBS). An autoimmune process has been postulated as the underlying
      pathophysiology. Most of the reported cases of GBS after bariatric surgery are of
      the axonal variety. Here, we report a case of a demyelinating variety of GBS in a
      young woman who presented with acute onset of progressive weakness and
      paresthesia of all limbs within six weeks after bariatric surgery. She was
      treated with intravenous immunoglobulin (IVIG) and rehabilitation. She had
      complete recovery on follow-up. We believe that onset of acute inflammatory
      demyelinating polyradiculoneuropathy (AIDP), which is demyelinating variety of
      GBS, is associated with changes in immune system after bariatric surgery. 

PMID- 25765351
TI  - Chylous ascites following retroperitoneal lymphadenectomy in gynecologic
      malignancies: incidence, risk factors and management.
AB  - INTRODUCTION: Chylous ascites is a rare form of ascites that results from
      accumulated lymph fluid in the peritoneal cavity caused by blocked or disrupted
      lymph flow through the major lymphatic channels. In the present study, our aim
      was to analyze the incidence, risk factors, diagnostic evaluation and management
      of chylous ascites after lymphadenectomy in gynecologic malignancies. METHODS: A
      total of 458 patients who had undergone staging surgery for gynecologic
      malignancies at our institution between January 2010 and December 2013 were
      retrospectively reviewed. After the exclusion criteria were applied, 399 patients
      were divided into 2 groups based on the presence (n = 36) or absence (n = 363) of
      chylous ascites. RESULTS: Among the 399 patients, 36 (9%) developed chylous
      ascites. The median time to onset was 4 days (range, 2-7 days). The analysis of
      the various features of lymphadenectomy showed that the number of para-aortic
      lymph nodes (PALNs) removed was significantly greater in the patients with
      chylous ascites (p < 0.001). A cut-off value of >14 PALNs was a good predictor of
      chylous ascites. In all patients, chylous ascites resolved with conservative
      management. CONCLUSIONS: Postoperative chylous ascites was strongly associated
      with the number of harvested PALNs. According to our findings, we suggest that
      conservative treatment should be the first step in managing patients with chylous
      ascites. Using an abdominal drain after surgery seems to be an effective
      diagnostic tool and treatment method for chylous ascites.

PMID- 25765352
TI  - Design, synthesis and evaluation of a series of non-steroidal anti-inflammatory
      drug conjugates as novel neuroinflammatory inhibitors.
AB  - Neuroinflammation is involved in the process of several central nervous system
      (CNS) diseases such as Parkinson's disease, Alzheimer's disease, ischemia and
      multiple sclerosis. As the macrophages in the central nervous system, microglial
      cell function in the innate immunity of the brain and are largely responsible for
      the inflammation-mediated neurotoxicity. Prevention of microglia activation might
      alleviate neuronal damage and degeneration under the inflammatory conditions, and
      therefore, represents a possible therapeutic approach to the aforementioned CNS
      diseases. Here we report the synthesis of a number of non-steroidal anti
      inflammatory drug (NSAID) conjugates, and the evaluation of their anti
      inflammatory effects in lipopolysaccharide (LPS)-stimulated BV-2 microglial cells
      and primary mouse microglial cells. Among the tested analogues, compounds 8 and
      11 demonstrated potent inhibition of nitric oxide production with no or weak cell
      toxicity. Compound 8 also significantly suppressed the expression of tumor
      necrosis factor (TNF)-alpha, interleukin (IL)-6, cyclooxygenase (COX)-2 as well
      as inducible nitric oxide synthase (iNOS) in LPS-stimulated BV-2 microglial
      cells. Further mechanistic studies indicated that compound 8 significantly
      suppressed phosphorylation of mitogen-activated protein kinases (MAPKs) and
      subsequent activation of activator of transcription 1 (AP-1). Furthermore, in a
      co-culture system, compound 8 inhibited the cytotoxicity generated by LPS
      activated microglia toward HT-22 neuroblastoma cells. Collectively, these
      experimental results demonstrated that compound 8 possessed potent anti
      neuroinflammatory activity via inhibition of microglia activation, and might
      serve as a potential lead for the therapeutic treatment of neuroinflammatory
      diseases. 

PMID- 25765353
TI  - Positive clinical outcome with IVIg as monotherapy in recurrent pemphigoid
      gestationis.
AB  - Pemphigoid gestationis (PG) is an autoimmune blistering disease associated with
      pregnancy. It is characterized by the presence of autoantibodies against bullous
      pemphigoid antigens in the basement membrane zone. A 32 year old female developed
      PG in the first pregnancy and had a stillbirth. PG recurred during the second
      trimester of her second pregnancy. Systemic corticosteroid therapy was cause for
      concern since patient developed gestational diabetes. Patient was unwilling to
      use insulin. Intravenous immunoglobulin (IVIg) was used as a treatment of last
      resort. The dose was 2g/kg/cycle. It was given every two weeks antepartum and
      every three weeks for three months postpartum. PG improved within four weeks of
      IVIg therapy. Serum and tissue immunopathological studies were negative prior to
      delivery. A healthy neonate was born. No adverse events to IVIg were observed. No
      disease was observed ten months postpartum.

PMID- 25765354
TI  - Differential expression of interferon alpha inducible genes in peripheral blood
      mononuclear cells from patients chronically infected with hepatitis C virus and
      healthy donors.
AB  - The impact of exposure to interferon-alpha (IFN-alpha) on gene expression in
      peripheral blood mononuclear cells (PBMC) from hepatitis C virus (HCV)-infected
      and healthy individuals was investigated to recognize whether their PBMC differ
      in expression of IFN-inducible genes (ISGs) following treatment with IFN-alpha2b.
      PBMC obtained from healthy and treatment-naive HCV-infected patients were
      cultured with IFN-alpha2b for 30min, 2h, 4h and 72h, and gene expression was
      analyzed using mRNA microarray technology. IFN-alpha caused differential up
      regulation of many known ISGs in PBMC from both HCV-infected and healthy
      subjects. In comparison to untreated controls, the highest augmentation in PBMC
      ISG expression occurred after 4-hour exposure to IFN-alpha2b in both groups. The
      analysis identified 84 transcripts, representing 64 known and 2 unknown genes,
      that were up-regulated by at least 5-fold in PBMC from infected and uninfected
      individuals. However, the expression of IFN-alpha inducible genes was impaired in
      the PBMC from HCV-infected individuals compared to healthy controls. This was due
      to an increased baseline expression of the transcripts in PBMC of HCV-infected
      patients. These findings expand our understanding of IFN-responses in HCV
      infected individuals and suggest that functions of PBMC, which include immune
      effector cells, are altered in patients chronically infected with HCV. 

PMID- 25765355
TI  - Diabetic peripheral neuropathy compromises balance during daily activities.
AB  - OBJECTIVE: Patients with diabetes with peripheral neuropathy have a well
      recognized increased risk of falls that may result in hospitalization. Therefore
      this study aimed to assess balance during the dynamic daily activities of walking
      on level ground and stair negotiation, where falls are most likely to occur.
      RESEARCH DESIGN AND METHODS: Gait analysis during level walking and stair
      negotiation was performed in 22 patients with diabetic neuropathy (DPN), 39
      patients with diabetes without neuropathy (D), and 28 nondiabetic control
      subjects (C) using a motion analysis system and embedded force plates in a
      staircase and level walkway. Balance was assessed by measuring the separation
      between the body center of mass and center of pressure during level walking,
      stair ascent, and stair descent. RESULTS: DPN patients demonstrated greater (P <
      0.05) maximum and range of separations of their center of mass from their center
      of pressure in the medial-lateral plane during stair descent, stair ascent, and
      level walking compared with the C group, as well as increased (P < 0.05) mean
      separation during level walking and stair ascent. The same group also
      demonstrated greater (P < 0.05) maximum anterior separations (toward the
      staircase) during stair ascent. No differences were observed in D patients.
      CONCLUSIONS: Greater separations of the center of mass from the center of
      pressure present a greater challenge to balance. Therefore, the higher medial
      lateral separations found in patients with DPN will require greater muscular
      demands to control upright posture. This may contribute to explaining why
      patients with DPN are more likely to fall, with the higher separations placing
      them at a higher risk of experiencing a sideways fall than nondiabetic control
      subjects.

PMID- 25765356
TI  - Cardiorespiratory fitness and incident diabetes: the FIT (Henry Ford ExercIse
      Testing) project.
AB  - OBJECTIVE: Prior evidence has linked higher cardiorespiratory fitness with a
      lower risk of diabetes in ambulatory populations. Using a demographically diverse
      study sample, we examined the association of fitness with incident diabetes in
      46,979 patients from The Henry Ford ExercIse Testing (FIT) Project without
      diabetes at baseline. RESEARCH DESIGN AND METHODS: Fitness was measured during a
      clinician-referred treadmill stress test performed between 1991 and 2009.
      Incident diabetes was defined as a new diagnosis of diabetes on three separate
      consecutive encounters derived from electronic medical records or administrative
      claims files. Analyses were performed with Cox proportional hazards models and
      were adjusted for diabetes risk factors. RESULTS: The mean age was 53 years with
      48% women and 27% black patients. Mean metabolic equivalents (METs) achieved was
      9.5 (SD 3.0). During a median follow-up period of 5.2 years (interquartile range
      2.6-8.3 years), there were 6,851 new diabetes cases (14.6%). After adjustment,
      patients achieving >=12 METs had a 54% lower risk of incident diabetes compared
      with patients achieving <6 METs (hazard ratio 0.46 [95% CI 0.41, 0.51]; P-trend <
      0.001). This relationship was preserved across strata of age, sex, race, obesity,
      hypertension, and hyperlipidemia. CONCLUSIONS: These data demonstrate that higher
      fitness is associated with a lower risk of incident diabetes regardless of
      demographic characteristics and baseline risk factors. Future studies should
      examine the association between change in fitness over time and incident
      diabetes.

PMID- 25765357
TI  - Relations between subclinical disease markers and type 2 diabetes, metabolic
      syndrome, and incident cardiovascular disease: the Jackson Heart Study.
AB  - OBJECTIVE: The presence of subclinical disease measures has been directly
      associated with the development of cardiovascular disease (CVD) in whites.
      African Americans (AAs) in the U.S. are at higher risk of CVD compared with non
      Hispanic whites; however, data on the prevalence of subclinical disease measures
      in AAs and their association to CVD remain unclear and may explain the higher CVD
      risk in this group. RESEARCH DESIGN AND METHODS: We evaluated 4,416 participants
      attending the first examination of the Jackson Heart Study (mean age 54 years;
      64% women) with available subclinical disease measures. RESULTS: There were 1,155
      participants (26%) with subclinical disease, defined as the presence of one or
      more of the following: peripheral arterial disease, left ventricular hypertrophy,
      microalbuminuria, high coronary artery calcium (CAC) score, and low left
      ventricular ejection fraction. In cross-sectional analyses using multivariable
      adjusted logistic regression, participants with metabolic syndrome (MetS) or
      diabetes (DM) had higher odds of subclinical disease compared with those without
      MetS and DM (odds ratios 1.55 [95% CI 1.30-1.85] and 2.86 [95% CI 2.32-3.53],
      respectively). Furthermore, the presence of a high CAC score and left ventricular
      hypertrophy were directly associated with the incidence of CVD (265 events) in
      multivariable-adjusted Cox proportional hazards regression models (P < 0.05). In
      prospective analyses, having MetS or DM significantly increased the hazard of
      incident CVD, independent of the presence of subclinical disease (P < 0.001).
      CONCLUSIONS: In our community-based sample of AAs, we observed a moderately high
      prevalence of subclinical disease, which in turn translated into a greater risk
      of CVD, especially in people with MetS and DM.

PMID- 25765358
TI  - Early serum human chorionic gonadotropin (hCG) trends after medication abortion.
AB  - OBJECTIVES: Despite increased reliance on human chorionic gonadotropin (hCG) for
      early pregnancy monitoring, there is limited information about hCG trends soon
      after medication abortion. The purpose of this study was to determine if there is
      a predictable decline in serum hCG values shortly after medication abortion.
      STUDY DESIGN: This is a retrospective study of women with early intrauterine
      pregnancies who underwent medication abortion with mifepristone and misoprostol
      and had a serum hCG level on Day 1 (day of mifepristone) and a repeat value on
      Day 2 to 6. The percent hCG decline was calculated from baseline to repeat
      measure, with repeat values from the same patient accounted for through repeated
      measure analysis of variance. RESULTS: Eighty-eight women with a mean gestational
      age of 5.5 weeks and median baseline hCG of 5220 IU met study criteria over a 3
      year period. The mean decline (+/-SD) in hCG from the Day 1 baseline value was
      56.9%+/-29.5% on Day 3, 73.5%+/-38.6% on Day 4, 86.1%+/-8.8% on Day 5, and
      92.9%+/-3.4% on Day 6. Eighty-two women (93% of the cohort) had a complete
      abortion without further intervention. The least square means hCG decline among
      these women was 57.6% [95% confidence interval (CI): 50.3-64.9%] on Day 3, 78.9%
      (95% CI: 75.0-82.8%) on Day 4 and 86.2% (95% CI: 81.3-91.1%) on Day 5.
      CONCLUSION: There is a rapid decline in serum hCG within the first few days after
      early medication abortion. Further research is needed to delineate how soon after
      medication abortion this decline may be specific enough to confirm abortion
      completion. IMPLICATIONS: This study provides the largest cohort of patients
      followed with serial hCG values in the first few days after medication abortion.
      Our findings demonstrate the trend in hCG decline in this population, which may
      be predictable by Day 5.

PMID- 25765359
TI  - Identification and characterization of in vitro and in vivo metabolites of
      steroidal alkaloid veratramine.
AB  - Veratramine, a steroidal alkaloid originating from Veratrum nigrum L., has
      demonstrated distinct anti-tumor and anti-hypertension effects, however, its
      metabolism has rarely been explored. The objective of the current study was to
      provide a comprehensive investigation of its metabolic pathways. The in vitro
      metabolic profiles of veratramine were evaluated by incubating it with liver
      microsomes and cytosols. The in vivo metabolic profiles in plasma, bile, urine
      and feces were monitored by UPLC-MS/MS after oral (20 mg/kg) and i.v. (50 ug/kg)
      administration in rats. Meanwhile, related P450s inhibitors and recombinant P450s
      and SULTs were used to identify the isozymes responsible for its metabolism.
      Eleven metabolites of veratramine, including seven hydroxylated, two sulfated and
      two glucuronidated metabolites, were characterized. Unlike most alkaloids, the
      major reactive sites of veratramine were on ring A and B instead of on the amine
      moiety. CYP2D6 was the major isozyme mediating hydroxylation, and substrate
      inhibition was observed with a Vmax , Ki and Clint of 2.05 +/- 0.53 nmol/min/mg,
      33.08 +/- 10.13 u m and 13.58 +/- 1.27 uL/min/mg. SULT2A1, with Km , Vmax and
      Clint values of 19.37 +/- 0.87 u m, 1.51 +/- 0.02 nmol/min/mg and 78.19 +/- 8.57
      uL/min/mg, was identified as the major isozyme contributing to its sulfation. In
      conclusion, CYP2D6 and SULT2A1 mediating hydroxylation and sulfation were
      identified as the major biotransformation for veratramine.

PMID- 25765360
TI  - The possible involvement of salicylic acid and hydrogen peroxide in the systemic
      promotion of phenolic biosynthesis in clover roots colonized by arbuscular
      mycorrhizal fungus.
AB  - Arbuscular mycorrhizal fungal (AMF) colonization can induce both the local and
      the systemic increase in phenolic accumulation in hosts. However, the signaling
      molecules responsible for the systemic induction is still unclear. In this study,
      a split-root rhizobox system was designed to explore these molecules, with one
      half of clover (Trifolium repense) roots colonized by AMF, Funneliformis mosseae
      (formerly known as Glomus mosseae), and the other not (NM/M). Plants with two
      halves both (M/M) or neither (NM/NM) inoculated were also established for
      comparison. The contents of phenols and the accumulation of salicylic acid (SA),
      hydrogen peroxide (H2O2) and nitric oxide (NO) in roots were monitored, the
      activities of L-phenylalanine ammonia-lyase (PAL) and nitric oxide synthase (NOS)
      in roots were assayed, and the expressions of pal and chs (gene encoding chalcone
      synthase) genes in roots were also quantified using qRT-PCR. Results indicated
      that when phenolic content in NM/NM plants was lower than that in M/M plants, AMF
      colonization systemically induced the increase in phenolic content in NM/M
      plants. Similarly, the accumulations of SA and H2O2 were increased by AMF both
      locally and systemically, while that of NO was only increased locally. Moreover,
      enzyme assay and qRT-PCR were in accordance with these results. These data
      suggest that AMF colonization can systemically increase the phenolic
      biosynthesis, and SA and H2O2 are possibly the signaling molecules involved. The
      role of MeSA, a signaling molecule capable of long distance transport in this
      process, is also discussed.

PMID- 25765361
TI  - Characterization of soluble acyl-ACP desaturases from Camelina sativa, Macadamia
      tetraphylla and Dolichandra unguis-cati.
AB  - Acyl-acyl carrier protein (ACP) desaturases (EC 1.14.19.2) are soluble enzymes
      that catalyse the insertion of a double bond into saturated fatty acid bound in
      saturated acyl chains bound to ACP in higher plants, producing cis
      monounsaturated fatty acids. Three types of soluble acyl-ACP desaturases have
      been described: Delta(9)-acyl-ACP, Delta(6)-acyl-ACP and Delta(4)-acyl-ACP
      desaturases, which differ in the substrate specificity and the position in which
      the double bond is introduced. In the present work, Camelina sativa (CsSAD),
      Macadamia tetraphylla (MtSAD) and Dolichandra unguis-cati (DuSAD) desaturases
      were cloned, sequenced and characterized. Single copies of CsSAD, MtSAD and DuSAD
      with three, one and two different alleles, respectively, were found. The
      corresponding mature proteins were heterologously expressed in Escherichia coli
      for biochemical characterization in protein extracts. The recombinant CsSAD
      enzyme showed 300-fold higher specificity towards 18:0-ACP than 16:0-ACP. Similar
      profile exhibited MtSAD although the differences in the specificity were lower,
      around 170-fold higher for 18:0-ACP than 16:0-ACP. Furthermore, DuSAD presented a
      profile showing preference towards 16:0-ACP against 18:0-ACP, around twice more,
      being so a Delta(9) palmitoyl-ACP desaturase. Also, we reported the expression
      profile of CsSAD, which showed the highest levels of expression in expanding
      tissues that typically are very active in lipid biosynthesis such as developing
      seed endosperm. Moreover, the possibility to express a new desaturase in C.
      sativa (oilseed crop that store high levels of oil and is easy to transform) to
      create a new line rich in short monounsaturated fatty acid is discussed. 

PMID- 25765363
TI  - Catching the tip of the iceberg - evaluation of sample preparation protocols for
      metaproteomic studies of the rumen microbiota.
AB  - Various metabolic processes are performed in the rumen caused by a complex
      microbiota comprising bacteria, archaea, protozoa, and fungi. Thus, the
      description of the active microbial fraction and their functions are of great
      interest for animal nutrition, biotechnology, and climatology. Metaproteomic
      studies of the rumen microbiota are challenged by the need of optimized sample
      preparation protocols in order to retrieve an enhanced amount of prokaryotic
      instead of plant- and bovine-derived cells before protein extraction and
      subsequent LC-MS/MS analysis. The present study evaluates three different
      protocols applied to the rumen microbiota either attached to plant fibers or
      present as planktonic cells. The findings of our work suggest the integration of
      cheesecloth-gauze filtration in sample preparation to achieve a better protein
      identification ratio. Our data have been deposited to ProteomeXchange with
      identifier PXD001526
      (http://proteomecentral.proteomexchange.org/dataset/PXD001526). 

PMID- 25765362
TI  - Transcriptome comparison of Cabernet Sauvignon grape berries from two regions
      with distinct climate.
AB  - Primary and secondary metabolism in grape berries is under the control of complex
      interactions among environmental conditions, genotypes, and management practices.
      To obtain an interpretation from the view of transcriptome on distinct metabolite
      accumulation between ecologically different regions in China, next-generation
      sequencing technology was performed on E-L 31, 35, and 38 stages of Cabernet
      Sauvignon grape berries from Changli (CL, eastern) and Gaotai (GT, western). The
      transcript abundance of epoxycarotenoid dioxygenase and xanthoxin dehydrogenase
      required for ABA biosynthesis was significantly higher in the GT berries at E-L
      35 and 38 stages compared with the CL berries, which may explain the relatively
      short maturation period of berries in the western region. Some genes required for
      carbohydrate metabolism, such as hexose transporter, L-idonate dehydrogenase, and
      phosphoenolpyruvate carboxylase, were significantly up-regulated in the CL
      berries in relation to the GT berries, which positively correlated with the sugar
      and organic acid accumulations. Pathway enrichment analysis of differentially
      expressed genes revealed that the CL berries had higher levels of phenylpropanoid
      biosynthesis at E-L 38 stage than the GT berries, which may relate to the quick
      fading of the GT wines because of weak co-pigmentation. This observation lays a
      foundation for further study concerning the molecular basis for environmental
      effects on berry quality formation.

PMID- 25765364
TI  - Chemical remodeling of cell-surface sialic acids through a palladium-triggered
      bioorthogonal elimination reaction.
AB  - We herein report a chemical decaging strategy for the in situ generation of
      neuramic acid (Neu), a unique type of sialic acid, on live cells by the use of a
      palladium-mediated bioorthogonal elimination reaction. Palladium nanoparticles
      (Pd NPs) were found to be a highly efficient and biocompatible depropargylation
      catalyst for the direct conversion of metabolically incorporated N
      (propargyloxycarbonyl)neuramic acid (Neu5Proc) into Neu on cell-surface glycans.
      This conversion chemically mimics the enzymatic de-N-acetylation of N
      acetylneuramic acid (Neu5Ac), a proposed mechanism for the natural occurrence of
      Neu on cell-surface glycans. The bioorthogonal elimination was also exploited for
      the manipulation of cell-surface charge by unmasking the free amine at C5 to
      neutralize the negatively charged carboxyl group at C1 of sialic acids. 

PMID- 25765365
TI  - Densities of rectal peptide YY and somatostatin cells as biomarkers for the
      diagnosis of irritable bowel syndrome.
AB  - Irritable bowel syndrome (IBS) is a common chronic disorder. IBS diagnosis is a
      diagnosis of exclusion since there are no blood tests, radiological or endoscopic
      examinations for this disorder. Although several attempts have been made to
      develop a symptoms-based diagnosis, such systems are not widely used in clinics.
      Several tests and examinations measuring pathological findings in IBS have been
      considered for the diagnosis of IBS, but none of them has proved useful as a
      biomarker. Abnormalities in the cell densities of rectal peptide YY (PYY) and
      somatostatin cells have been reported in IBS patients. The aim of the present
      study was to determine the utility of these abnormalities as biomarkers for the
      diagnosis of IBS. Patients with IBS established according to Rome III criteria (n
      = 101) were included in this study (71 females and 30 males with a mean age of 35
      years; range 18-61 years), and 62 healthy subjects (38 females and 24 males with
      a mean age of 41 years; range 18-65 years) were recruited as controls. Both the
      patients and controls underwent colonoscopy during which rectal biopsy samples
      were taken. The tissue samples were immunostained for PYY and somatostatin, and
      the number of stained cells was quantified relative to both the area of
      epithelial cells and per microscopic field. The density of PYY cells was
      significantly lower in IBS patients than in the healthy controls (P < 0.0001);
      receiver operator characteristic (ROC) analysis revealed an area under the ROC
      curve (AUC) of 0.99. The somatostatin cell density in IBS patients was higher
      than in the controls (P < 0.0001); ROC analysis revealed an AUC of 0.86. The
      densities of the rectal PYY and somatostatin cells appear to be clinically
      effective biomarkers for IBS. Furthermore, measurement of these parameters is
      inexpensive, rapid and does not require considerable experience or sophisticated
      equipment.

PMID- 25765366
TI  - Diagnostic accuracy of cone-beam computed tomography in the evaluation of chronic
      rhinosinusitis.
AB  - INTRODUCTION: This study assessed the agreement of cone-beam computed tomography
      (CBCT) scan and sinus endoscopy findings and attempted to find a diagnostic
      accuracy of CBCT in patients with chronic rhinosinusitis (CRS). METHODS: Forty
      two patients with CRS referred to the Aria and 22 Bahman Hospitals in Mashhad,
      Iran, during the year 2011 were included in this cross-sectional study. Paranasal
      sinus CBCT scanning and endoscopy were performed in all patients. The
      sensitivity, specificity, positive and negative predictive values (PPV and NPV),
      and accuracy of CBCT were determined, and the agreement between CBCT and
      endoscopy findings was evaluated. RESULTS: In most of our findings, except for
      infundibulum thickening, there was a strong agreement between CBCT and paranasal
      sinus endoscopy, with a kappa coefficient >0.80 (p < 0.05). The sensitivity,
      specificity, PPV, NPV, and accuracy of CBCT were >80% for most of the findings,
      except for infundibulum thickening and septal deviation. CONCLUSION: CBCT has
      nearly the same diagnostic accuracy as sinus endoscopy. The accuracy of CBCT
      scanning is high, and CBCT findings are well correlated with sinus endoscopy
      findings. Considering its high accuracy and lower costs and radiation doses, CBCT
      may be a proper alternative method for diagnostic sinus endoscopy in the
      assessment of CRS in patients with a contraindication for sinus endoscopy.

PMID- 25765368
TI  - Amphibians crossing the Bering Land Bridge: evidence from holarctic treefrogs
      (Hyla, Hylidae, Anura).
AB  - Based on an updated, time-calibrated phylogeny and applying biogeographical model
      testing and diversification analysis, we re-examined systematics and biogeography
      of the Holarctic treefrog genus Hyla with a focus on the East Asian species. We
      analyzed four mitochondrial genes (12S and 16S rRNA, tRNA(Leu), ND1) and one
      nuclear gene (POMC) for 192 samples representing 30 species of Hyla. Based on our
      results we suggest that H. ussuriensis is a synonym of H. japonica. Specimens
      from Sakhalin and Kunashir Islands might represent a cryptic species within H.
      japonica. We confirm earlier hypotheses that the genus Hyla originated during the
      Eocene to Early Oligocene and that Eurasian species originated from two
      independent dispersal events from North America via the Bering Land Bridge.
      Middle Eocene to Oligocene dispersal gave rise to the most recent common ancestor
      of the West Palearctic H. arborea-group and the East Palearctic, newly defined,
      H. chinensis-group. The Northeast Asian H. japonica-group resulted from a second
      wave of colonization from the Nearctic. A trans-Atlantic dispersal route could be
      excluded. Dispersal of the H. arborea-group to the western Palearctic coincides
      with the closure of the Turgai Strait at the end of the Oligocene.
      Diversification of Hyla decreased at the end of the Middle Miocene, possibly
      coinciding with the end of the Mid Miocene Climatic Optimum and the advent of
      cooler and drier climates in the Northern Hemisphere. 

PMID- 25765367
TI  - Male-specific submaxillary gland protein, a lipocalin allergen of the golden
      hamster, differs from the lipocalin allergens of Siberian and Roborovski dwarf
      hamsters.
AB  - BACKGROUND: An increasing number of asthma cases upon exposure to hamsters and
      anaphylactic reactions following hamster bites are being reported, but the
      allergens responsible are still poorly characterized. In the Golden hamster, male
      specific submaxillary gland protein (MSP), a lipocalin expressed in a sex- and
      tissue-specific manner in the submaxillary and lacrimal glands, is secreted in
      the saliva, tears and urine. The purpose of this study was to determine if MSP is
      an allergen, to identify IgE-reactive proteins of different hamster species and
      to analyse potential cross-reactivities. METHODS: Fur extracts were prepared from
      four hamster species. Hamster-allergic patients were selected based on a history
      of positive IgE-test to hamster epithelium. The IgE-reactivity of patients' sera
      was investigated by means of immunoblot and ELISA. IgE-reactive proteins in fur
      extracts and the submaxillary gland were identified using anti-MSP antibodies,
      Edman sequencing or mass spectrometry. MSP was purified from Golden hamster and
      recombinant MSP was expressed in E. coli. RESULTS: Four patients had IgE
      antibodies against 20.5-kDa and 24-kDa proteins of Golden hamster fur extract,
      which were identified as MSP. IgE-reactive MSP-like proteins were detected in
      European hamster fur extract. Three patient sera showed IgE-reactive bands at 17
      21 kDa in Siberian and Roborovski hamster fur extracts. These proteins were
      identified as two closely related lipocalins. Immunoblot inhibition experiments
      showed that they are cross-reactive and are different from MSP. CONCLUSION: MSP
      lipocalin of the Golden hamster was identified as an allergen, and it is
      different from the cross-reactive lipocalin allergens of Siberian and Roborovski
      hamsters. Our findings highlight the need for specific tools for the in vitro and
      in vivo diagnosis of allergy to different hamster species.

PMID- 25765369
TI  - Transformative power of technology.

PMID- 25765371
TI  - The Atmospheric Oxidation Mechanism of Benzyl Alcohol Initiated by OH Radicals:
      The Addition Channels.
AB  - Benzyl alcohol (BA) is present in indoor atmospheres, where it reacts with OH
      radicals and undergoes further oxidation. A theoretical study is carried out to
      elucidate the reaction mechanism and to identify the main products of the
      oxidation of BA that is initiated by OH radicals. The reaction is found to
      proceed by H-abstraction from the CH2 group (25 %) and addition to the ipso (60
      %) and ortho (15 %) positions of the aromatic ring. The BA-OH adducts react
      further with O2 via the bicyclic radical intermediates-the same way as for
      benzene-forming mainly 3-hydroxy-2-oxopropanal and butenedial. If NOx is low, the
      bicyclic peroxy radicals undergo intramolecular H-migration, forming products
      containing OH, OOH, and CH2 OH/CHO functional groups, and contribute to secondary
      organic aerosol (SOA) formation.

PMID- 25765370
TI  - Survival and quality of life for children with end-stage heart failure who are
      not candidates for cardiac transplant.
AB  - BACKGROUND: Some pediatric patients referred for heart transplant (HTx) are sub
      optimal candidates. Their outcomes without HTx are presumed to be dismal, but
      have not been well described. Knowledge about their outcomes is critical when
      weighing the risks between a high-risk transplant and "terminal" palliation.
      METHODS: We retrospectively reviewed all HTx referrals from January 2005 to July
      2013. We excluded those who were listed for HTx, or who were denied HTx due to
      being "too well," seeking only those who were in need of but not suitable for
      HTx. End-points included mortality and length of survival. RESULTS: Of 212
      referrals, 39 (19%) (age 0 to 19 years, median 3.5 years) were denied HTx for
      reasons other than being too well. Twenty-eight (72%) had palliated congenital
      heart disease. Overall mortality during the follow-up period was 38% (n = 15)
      with a median follow-up time of 195 days (8 to 2,832 days). Ten patients received
      subsequent cardiac surgery with 1 death (10%) and median follow-up of 2.6 years.
      Mortality risk was not influenced by age, weight, growth failure, congenital
      heart disease or single-ventricle physiology. Mechanical ventilation (hazard
      ratio 6.31, p = 0.001) and inotrope dependence (hazard ratio 4.79, p = 0.006)
      were associated with the highest risk of mortality. Quality of life was measured
      with the PedsQL cardiac module and completed by 11 of 16 eligible patients with
      an overall average score of 70.2 +/- 23.9. CONCLUSIONS: An advanced heart failure
      program can achieve satisfactory results for pediatric patients who are not
      suitable candidates for HTx. For some children, high-risk palliative surgery can
      result in better outcome than high-risk HTx. Mortality was related to the degree
      of heart failure at presentation rather than underlying heart disease.

PMID- 25765373
TI  - Push-Pull Buta-1,2,3-trienes: exceptionally low rotational barriers of cumulenic
      C=C bonds and proacetylenic reactivity.
AB  - A variety of asymmetrically donor-acceptor-substituted [3]cumulenes (buta-1,2,3
      trienes) were synthesized by developed procedures. The activation barriers to
      rotation DeltaG(?) were measured by variable temperature NMR spectroscopy and
      found to be as low as 11.8 kcal mol(-1) , in the range of the barriers for
      rotation around sterically hindered single bonds. The central C=C bond of the
      push-pull-substituted [3]cumulene moiety is shortened down to 1.22 A as measured
      by X-ray crystallography, leading to a substantial bond length alternation (BLA)
      of up to 0.17 A. All the experimental results are supported by DFT calculations.
      Zwitterionic transition states (TS) of bond rotation confirm the postulated
      proacetylenic character of donor-acceptor [3]cumulenes. Additional support for
      the proacetylenic character of these chromophores is provided by their reaction
      with tetracyanoethene (TCNE) in a cycloaddition-retroelectrocyclization (CA-RE)
      cascade characteristic of donor-polarized acetylenes.

PMID- 25765372
TI  - Self-calibrated trajectory estimation and signal correction method for robust
      radial imaging using GRAPPA operator gridding.
AB  - PURPOSE: In radial imaging, projections may become "miscentered" due to gradient
      errors such as delays and eddy currents. These errors may result in image
      artifacts and can disrupt the reliability of direct current (DC) navigation. The
      proposed parallel imaging-based technique retrospectively estimates trajectory
      error from miscentered radial data without extra acquisitions, hardware, or
      sequence modification. THEORY AND METHODS: After phase correction, self
      calibrated GRAPPA operator gridding (GROG) weights are iteratively applied to
      shift-miscentered projections toward the center of k-space. A search algorithm
      identifies the shift that aligns the peak k-space signals by maximizing the sum
      of-squares DC signal estimate of each projection. The algorithm returns a
      trajectory estimate and a corrected radial k-space signal. RESULTS: Data from a
      spherical phantom, the head, and the heart demonstrate that image reconstruction
      with the estimated trajectory restores image quality and reduces artifacts such
      as streaks and signal voids. The DC signal level is increased and variability is
      reduced. CONCLUSION: Retrospective phase correction and iterative application of
      GROG can be used to successfully estimate the trajectory error in two-dimensional
      radial acquisitions for improved image reconstruction without requiring extra
      data acquisition or sequence modification.

PMID- 25765374
TI  - Comparative toxicity of copper nanoparticles across three Lemnaceae species.
AB  - Metallic nanoparticles can end up in aquatic ecosystems due to their widespread
      application. Even though the toxicological effects of metallic nanoparticles to a
      diversity of species have been reported extensively, the toxicological data
      achieved in different studies are not always comparable and little is known
      regarding the comparative toxicity of nanoparticles across species, as different
      test strategies and endpoints were applied. To attempt to fill this knowledge
      gap, Spirodela polyrhiza, Lemna minor and Wolffia arrhiza were exposed to 25 nm
      spherical copper nanoparticles to investigate the inhibiting effect of copper
      nanoparticle suspensions across species at three endpoints: total frond area,
      frond number and dry weight based relative growth rate. The total frond area
      based relative growth rate was found to be the most sensitive endpoint, with an
      EC50 of 1.15+/-0.09 mg/L for S. polyrhiza, 0.84+/-0.12 mg/L for L. minor and
      0.64+/-0.05 mg/L for W. arrhiza. Both the particles and the copper ions
      contributed to the inhibiting effects of copper nanoparticle suspensions at all
      endpoints studied. Dose-response related inhibiting effects caused by the copper
      ions were found at all endpoints studied, whereas the particles only showed dose
      response related inhibiting effects on the total frond area based relative growth
      rate. This suggests that different physiological processes are involved in case
      of exposure to particles and copper ions. W. arrhiza was found to be the most
      sensitive species tested and S. polyrhiza was the least sensitive species tested,
      when the inhibiting effect was evaluated based on the relative growth rate
      calculated from total frond area. These findings exemplify the importance of
      identifying the suitable endpoints of toxicity assessment and considering the
      intrinsic differences between species when evaluating the toxicological profile
      of metallic nanoparticles across species.

PMID- 25765375
TI  - Acute toxicological effects on the earthworm Eisenia fetida of 18 common
      pharmaceuticals in artificial soil.
AB  - Following soil applications of recycled water and biosolids, pharmaceutical
      residues can eventually enter the terrestrial environment. In vitro and in vivo
      assays have largely focused on the acute ecotoxicity of these compounds in
      aquatic systems. However, studies on the ecotoxicological effects of
      pharmaceuticals in soil biota are especially scarce. The aim of this study was to
      investigate the acute toxicity of 18 pharmaceuticals (4 NSAIDs, 5 blood lipid
      lowering agents, 6 beta-blockers and 3 antibiotics) that are usually found in the
      environment by using an Eisenia fetida bioassay. In addition, the presence of
      these pharmaceuticals in artificial soil was verified at the end of the test. Our
      results indicate that seven of the studied drugs cause acute adverse effects in
      E. fetida, in particular, the NSAIDs and the blood lipid-lowering agents.
      Ibuprofen (LC50=64.80 mg/kg) caused the highest acute toxicity for all tested
      compounds, followed by diclofenac (LC50=90.49 mg/kg) and simvastatin (LC50=92.70
      mg/kg). Other tested pharmaceuticals from NSAIDs and blood lipid-lowering
      families have toxicity effects, from a LC50=140.87 mg/kg for gemfibrozil to
      795.07 mg/kg for lovastatin. Atorvastatin, bezafibrate, beta-blockers and
      antibiotics showed no detectable lethality in E. fetida. The four NSAIDs showed
      evidence of modification of their original chemical structure after 14 days so
      the detected toxicity may be due to the original product as well as their
      degradation products. The three blood lipid-lowering agents seem to be more
      stable in soil. From an environmental perspective, the lethal concentrations of
      the tested drugs are much greater than those reported in wastewater and
      biosolids, therefore acute toxic effects may be improbable. However, little is
      known about the accumulation of these substances in soils after regular
      applications, so accumulative and chronic effects cannot be excluded. Moreover,
      more studies are needed to determine the role of the degradation products of
      these pharmaceuticals on terrestrial toxicity.

PMID- 25765376
TI  - Effects of organism preparation in metallothionein and metal analysis in marine
      invertebrates for biomonitoring marine pollution.
AB  - Metallothionein (MT) is established as a potentially useful biomarker for
      monitoring aquatic pollution. This paper addresses widespread inconsistencies in
      storage conditions, tissue type selection and pre-treatment of samples before MT
      and metal analysis in biomarker studies. This variation hampers comparability and
      so the widespread implementation of this monitoring approach. Actively sampled
      Mytilus edulis in Southampton Water, UK were exposed to different storage
      temperatures, a variety of tissue types were analysed, and various pre-treatments
      of transportation on ice, transportation in seawater, depuration, and rapid
      dissection in the field were examined. Storage temperatures of -20  degrees C
      were found to be adequate for periods of at least ten weeks, as MT was not
      reduced by protein degradation compared with samples kept at -80  degrees C.
      Whole tissue and digestive gland concentrations of MT and metals were
      significantly positively correlated and directly relatable. MT in the digestive
      gland appeared to be more responsive to metals than in whole tissue, where it may
      be diluted, masking MT responses. However, longer study periods may suffer the
      effects of mass changes to the digestive gland, which alters MT concentration,
      and it may therefore be advisable to measure whole tissue. Depuration and
      transportation in seawater reduced both MT and metal concentrations in the
      digestive gland, and few correlations between MT and metals were identified for
      these treatments. It is therefore recommended that: i) samples are transported to
      the laboratory on ice and dissected as soon as possible thereafter, ii)
      depuration should not be used when examining MT response to metal exposure until
      further research clarifying its utility is reported, iii) either whole tissue or
      the digestive gland can be used to measure MT, though whole tissue may be
      preferable on long-term studies, and iv) organisms can be stored at -20  degrees
      C before analysis for up to ten weeks. These practices can be applied to future
      biomonitoring studies and will improve the comparability and repeatability of
      using MT as a biomarker.

PMID- 25765377
TI  - Spatial variability of ultraviolet-absorbing compounds in an aquatic liverwort
      and their usefulness as biomarkers of current and past UV radiation: a case study
      in the Atlantic-Mediterranean transition.
AB  - The spatial variability of ultraviolet-absorbing compounds (UVACs) in the
      freshwater liverwort Jungermannia exsertifolia subsp. cordifolia was studied in
      mid-latitudes (the Atlantic-Mediterranean transition) across a wide lati
      altitudinal gradient, with the aim of testing the usefulness of UVACs as
      biomarkers of current ambient levels of UV radiation. We analysed 17 samples from
      streams located in the main mountain ranges of the Iberian Peninsula,
      differentiating methanol-soluble (SUVACs, mainly located in the vacuoles) and
      methanol-insoluble (IUVACs, bound to cell walls) compounds, since they represent
      different manners to cope with UV radiation. In both fractions, the bulk level of
      UVACs and the concentrations of several individual compounds were measured. In
      addition, we measured Fv/Fm, DNA damage and sclerophylly index (SI) as possible
      additional UV biomarkers. UVACs showed a high variability, probably due not only
      to the gradients of macroenvironmental factors (UV radiation, PAR, and water
      temperature), but also to microenvironmental factors inherent to the dynamic
      nature of mountain streams. Two soluble coumarins were positively correlated with
      UV levels and could be used for ambient UV biomonitoring in the spatial scale. In
      contrast to the variability in UVACs, the relatively homogeneous values of Fv/Fm
      and the lack of any DNA damage made these variables useless for ambient UV
      biomonitoring, but suggested a strong acclimation capacity of this liverwort to
      changing environmental conditions (in particular, to UV levels). Finally, UVACs
      of fresh samples of the liverwort were compared to those of herbarium samples
      collected in the same lati-altitudinal gradient. SUVACs were significantly higher
      in fresh samples, whereas IUVACs generally showed the contrary. Thus, IUVACs were
      more stable than SUVACs and hence more adequate for retrospective UV
      biomonitoring. In conclusion, UVAC compartmentation should be taken into account
      for bryophyte-based UV biomonitoring in future studies. 

PMID- 25765378
TI  - Photochemical fate and eco-genotoxicity assessment of the drug etodolac.
AB  - The photochemical behavior of etodolac was investigated under various irradiation
      conditions. Kinetic data were obtained after irradiation of 10(-4) M aqueous
      solutions by UVB, UVA and direct exposure to sunlight. The Xenon lamp irradiation
      was used in order to determine the photodegradation quantum yield under sun
      simulated condition (phisun). The value was determined to be=0.10+/-0.01. In
      order to obtain photoproducts and for mechanistic purposes, experiments were
      carried out on more concentrated solutions by exposure to sunlight and to UVA and
      UVB lamps. The drug underwent photooxidative processes following an initial
      oxygen addition to the double bond of the five membered ring and was mainly
      converted into a spiro compound and a macrolactam. Ecotoxicity tests were
      performed on etodolac, its photostable spiro derivative and its sunlight
      irradiation mixture on two different aquatic trophic levels, plants (algae) and
      invertebrates (rotifers and crustaceans). Mutagenesis and genotoxicity were
      detected on bacterial strains. The results showed that only etodolac had long
      term effects on rotifers although at concentrations far from environmental
      detection values. A mutagenic and genotoxic potential was found for its
      derivative.

PMID- 25765379
TI  - Fundamental study on the development of fiber optic sensor for real-time sensing
      of CaCO3 scale formation in geothermal water.
AB  - This study proposes an optical fiber sensor for calcium carbonate (CaCO3) scale
      formation in water. The sensor is easily fabricated by removing the cladding of a
      multimode fiber to expose the core towards the surrounding medium in order to
      detect refractive index change. A variation of the transmittance response from
      the high refractive index of CaCO3 which precipitated on the fiber core surface
      was observed. The proposed setup can be used to analyze the transmittance
      response over wide range of wavelength using white light as a source and also a
      spectroscopy detector. The curve of the transmittance percentage over time showed
      that a fiber core with 200 MUm has higher sensitivity as compared to a fiber core
      with 400 MUm. The findings from this study showed that the sensor detection
      region at near infrared (NIR) wavelengths showed better sensitivity than visible
      light (VIS) wavelengths. Field tests were conducted using natural geothermal
      water at Matsushiro, Japan in order to verify the performance of the proposed
      sensor. The optical response was successfully evaluated and the analytical
      results confirmed the capability of monitoring scale formation in a geothermal
      water environment. 

PMID- 25765381
TI  - Re: Quality assessment of partial nephrectomy complications reporting using EAU
      standardised quality criteria.

PMID- 25765380
TI  - The Fidelity of p16 Staining as a Surrogate Marker of Human Papillomavirus Status
      in Fine-Needle Aspirates and Core Biopsies of Neck Node Metastases: Implications
      for HPV Testing Protocols.
AB  - OBJECTIVES: The importance of detecting human papillomavirus (HPV) in head and
      neck squamous cell carcinoma (HNSCC) has resulted in a growing expectation for
      HPV testing of clinical samples. Although testing protocols vary, most pertain to
      primary tumor biopsies/resections. Testing of fine-needle aspirates and core
      biopsies (FNACBs) is advantageous, but it is unclear whether technical and
      biological factors adversely affect the fidelity of HPV detection in these
      samples. METHODS: Data was collected for 85 patients with regionally metastatic
      HNSCC that had undergone FNACB with HPV analysis as part of clinical care. HPV
      testing consisted of p16 immunostaining and HPV in situ hybridization (ISH). The
      FNACBs were compared with the subsequent biopsies/resections for HPV status.
      RESULTS: p16 staining was present in 60 cases (71%). p16 positivity was
      predictive of oropharyngeal origin (p<0.001) and correlated with the presence of
      HPV by ISH (98% correlation). On comparison of the metastases and primary
      cancers, the HPV status was concordant in 58 of 59 cases (98%). CONCLUSIONS: For
      patients with metastatic HNSCC, p16 staining reliably reflects the HPV status of
      the primary tumor. p16 staining of FNACBs may obviate the need for more invasive
      sampling of the primary cancer solely for the purpose of HPV testing.

PMID- 25765382
TI  - Nephron sparing surgery for de novo kidney graft tumor: results from a
      multicenter national study.

PMID- 25765383
TI  - Re: MR imaging of urinary bladder cancer for T-staging: a review and a pictorial
      essay of diffusion-weighted imaging.

PMID- 25765384
TI  - Re: Surveillance of patients with bladder cancer following cystectomy: yield of
      CT urography.

PMID- 25765385
TI  - Re: Effect of radium-223 dichloride on symptomatic skeletal events in patients
      with castration-resistant prostate cancer and bone metastases: results from a
      phase 3, double-blind, randomised trial.

PMID- 25765386
TI  - Re: Prospective randomized phase 2 trial of intensity modulated radiation therapy
      with or without oncolytic adenovirus-mediated cytotoxic gene therapy in
      intermediate-risk prostate cancer.

PMID- 25765387
TI  - Re: Ipilimumab versus placebo after radiotherapy in patients with metastatic
      castration-resistant prostate cancer that had progressed after docetaxel
      chemotherapy (CA184-043): a multicentre, randomised, double-blind, phase 3 trial.

PMID- 25765388
TI  - Re: Retzius-sparing robot-assisted laparoscopic radical prostatectomy: combining
      the best of retropubic and perineal approaches.

PMID- 25765389
TI  - Re: Detecting positive surgical margins using single optical fiber probe during
      radical prostatectomy: a pilot study.

PMID- 25765390
TI  - Re: First salvage treatment in patients with advanced germ cell cancer after
      cisplatin-based chemotherapy: analysis of a registry of the German Testicular
      Cancer Study Group (GTCSG).

PMID- 25765391
TI  - Re: Atypical microorganisms in expressed prostatic secretion from patients with
      chronic prostatitis/chronic pelvic pain syndrome: microbiological results from a
      case-control study.

PMID- 25765392
TI  - Re: Enterococcus faecalis subverts and invades the host urothelium in patients
      with chronic urinary tract infection.

PMID- 25765393
TI  - Re: Oxalate content of food: a tangled web.

PMID- 25765394
TI  - Re: Randomized and double-blinded clinical trial of the safety and calcium kidney
      stone dissolving efficacy of Lapis judaicus.

PMID- 25765396
TI  - Re: Long-term urine biobanking: storage stability of clinical chemical parameters
      under moderate freezing conditions without use of preservatives.

PMID- 25765397
TI  - Re: Ultrasonography versus computed tomography for suspected nephrolithiasis.

PMID- 25765398
TI  - Re: Ultrasonography versus computed tomography for suspected nephrolithiasis.

PMID- 25765399
TI  - Re: Nephrocalcinosis is a risk factor for kidney failure in primary
      hyperoxaluria.

PMID- 25765400
TI  - Re: Ultrasound acoustic shadow width is an accurate predictor of kidney stone
      size.

PMID- 25765401
TI  - Re: a population-based analysis of contemporary rates of reoperation for penile
      prosthesis procedures.

PMID- 25765402
TI  - Re: High patient satisfaction of inflatable penile prosthesis insertion with
      synchronous penile plication for erectile dysfunction and Peyronie's disease.

PMID- 25765403
TI  - Re: A critical analysis of candidacy for penile revascularization.

PMID- 25765404
TI  - Re: Infections associated with inflatable penile prostheses.

PMID- 25765405
TI  - Re: A prospective study examining the association between preoperative frailty
      and postoperative complications in patients undergoing minimally invasive
      surgery.

PMID- 25765406
TI  - Re: Positioning-related complications of minimally invasive radical
      prostatectomies.

PMID- 25765407
TI  - Re: Comparison of 2 transvaginal surgical approaches and perioperative behavioral
      therapy for apical vaginal prolapse: the OPTIMAL randomized trial.

PMID- 25765408
TI  - Re: A review of the current status of laparoscopic and robot-assisted
      sacrocolpopexy for pelvic organ prolapse.

PMID- 25765409
TI  - Re: Outcomes of vaginal prolapse surgery among female Medicare beneficiaries: the
      role of apical support.

PMID- 25765410
TI  - Re: Adolescent urology: developing lifelong care for congenital anomalies.

PMID- 25765411
TI  - Re: Urinary incontinence in patients with Alzheimer's disease: relationship
      between symptom status and urodynamic diagnoses.

PMID- 25765412
TI  - Re: The efficacy and tolerability of the beta3-adrenoceptor agonist mirabegron
      for the treatment of symptoms of overactive bladder in older patients.

PMID- 25765413
TI  - Re: Systematic review and meta-analysis of randomized controlled trials
      evaluating silodosin in the treatment of non-neurogenic male lower urinary tract
      symptoms suggestive of benign prostatic enlargement.

PMID- 25765414
TI  - Re: Finasteride treatment alters tissue specific androgen receptor expression in
      prostate tissues.

PMID- 25765415
TI  - Re: Prospective masked comparison of intraoperative floppy iris syndrome severity
      with tamsulosin versus alfuzosin.

PMID- 25765416
TI  - Re: Renal vein extension during living-donor kidney transplantation in the era of
      hand-assisted laparoscopic living-donor nephrectomy.

PMID- 25765417
TI  - Re: Renal transplantation using belatacept without maintenance steroids or
      calcineurin inhibitors.

PMID- 25765418
TI  - Re: Health care coverage under the Affordable Care Act--a progress report.

PMID- 25765419
TI  - Re: The Affordable Care Act reduces emergency department use by young adults:
      evidence from three states.

PMID- 25765420
TI  - Re: Long-term effect of hospital pay for performance on mortality in England.

PMID- 25765421
TI  - Re: A comparison of hospital administrative costs in eight nations: US costs
      exceed all others by far.

PMID- 25765422
TI  - Re: American Geriatrics Society identifies another five things that healthcare
      providers and patients should question.

PMID- 25765423
TI  - Re: Prevalence and determinants of use of potentially inappropriate medications
      in elderly inpatients: a prospective study in a tertiary healthcare setting.

PMID- 25765424
TI  - Re: Inguinal approach for the management of unilateral non-palpable testis: is
      diagnostic laparoscopy necessary?

PMID- 25765425
TI  - Re: Diagnostic and management approaches to pediatric and adolescent varicocele:
      a survey of pediatric urologists.

PMID- 25765426
TI  - Re: Obesity and a febrile urinary tract infection: dual burden for young
      children?

PMID- 25765427
TI  - Re: Underuse of 24-hour urine collection among children with incident urinary
      stones: a quality-of-care concern?

PMID- 25765428
TI  - Re: Characteristics of TRK-130 (naltalimide), a novel opioid ligand, as a new
      therapeutic agent for overactive bladder.

PMID- 25765429
TI  - Re: Intravesical TRPV4 blockade reduces repeated variate stress-induced bladder
      dysfunction by increasing bladder capacity and decreasing voiding frequency in
      male rats.

PMID- 25765430
TI  - Re: Mutations in 3'-long terminal repeat of HERV-W family in chromosome 7
      upregulate syncytin-1 expression in urothelial cell carcinoma of the bladder
      through interacting with c-Myb.

PMID- 25765431
TI  - Re: Pharmacologic rescue of an enzyme-trafficking defect in primary hyperoxaluria
      1.

PMID- 25765433
TI  - Structural analysis of strained LaVO3 thin films.
AB  - While structure refinement is routinely achieved for simple bulk materials, the
      accurate structural determination still poses challenges for thin films due on
      the one hand to the small amount of material deposited on the thicker substrate
      and, on the other hand, to the intricate epitaxial relationships that
      substantially complicate standard x-ray diffraction analysis. Using both electron
      and x-ray diffraction, we analyze the crystal structure of epitaxial LaVO3 thin
      films grown on (1 0 0)-oriented SrTiO3. Transmission electron microscopy study
      reveals that the thin films are epitaxially grown on SrTiO3 and points to the
      presence of 90 degrees  oriented domains. The mapping of the reciprocal space
      obtained by high resolution x-ray diffraction permits refinement of the lattice
      parameters. We finally deduce that strain accommodation imposes a monoclinic
      structure onto the LaVO3 film. The reciprocal space maps are numerically
      processed and the extracted data computed to refine the atomic positions, which
      are compared to those obtained using precession electron diffraction tomography. 

PMID- 25765434
TI  - Polymethacrylate coated electrospun PHB fibers: An exquisite outlook for
      fabrication of paper-based biosensors.
AB  - Electrospun polyhydroxybutyrate (PHB) fibers were dip-coated by polymethyl
      methacrylate-co-methacrylic acid, poly(MMA-co-MAA), which was synthesized in
      different molar ratios of the monomers via free-radical polymerization.
      Fabricated platfrom was employed for immobilization of the dengue antibody and
      subsequent detection of dengue enveloped virus in enzyme-linked immunosorbent
      assay (ELISA). There is a major advantage for combination of electrospun fibers
      and copolymers. Fiber structre of electrospun PHB provides large specific surface
      area available for biomolecular interaction. In addition, polymer coated parts of
      the platform inherited the premanent presence of surface carboxyl (-COOH) groups
      from MAA segments of the copolymer which can be effectively used for covalent and
      physical protein immobilization. By tuning the concentration of MAA monomers in
      polymerization reaction the concentration of surface -COOH groups can be
      carefully controlled. Therefore two different techniques have been used for
      immobilization of the dengue antibody aimed for dengue detection: physical
      attachment of dengue antibodies to the surface and covalent immobilization of
      antibodies through carbodiimide chemistry. In that perspective, several different
      characterization techniques were employed to investigate the new polymeric fiber
      platform such as scanning electron microscopy (SEM), atomic force microscopy
      (AFM), water contact angle (WCA) measurement and UV-vis titration. Regardless of
      the immobilization techniques, substantially higher signal intensity was recorded
      from developed platform in comparison to the conventional ELISA assay. 

PMID- 25765435
TI  - A method for measuring the local gas pressure within a gas-flow stage in situ in
      the transmission electron microscope.
AB  - Environmental transmission electron microscopy (TEM) has enabled in situ
      experiments in a gaseous environment with high resolution imaging and
      spectroscopy. Addressing scientific challenges in areas such as catalysis,
      corrosion, and geochemistry can require pressures much higher than the ~20 mbar
      achievable with a differentially pumped environmental TEM. Gas flow stages, in
      which the environment is contained between two semi-transparent thin membrane
      windows, have been demonstrated at pressures of several atmospheres. However, the
      relationship between the pressure at the sample and the pressure drop across the
      system is not clear for some geometries. We demonstrate a method for measuring
      the gas pressure at the sample by measuring the ratio of elastic to inelastic
      scattering and the defocus of the pair of thin windows. This method requires two
      energy filtered high-resolution TEM images that can be performed during an
      ongoing experiment, at the region of interest. The approach is demonstrated to
      measure greater than atmosphere pressures of N2 gas using a commercially
      available gas-flow stage. This technique provides a means to ensure reproducible
      sample pressures between different experiments, and even between very differently
      designed gas-flow stages.

PMID- 25765436
TI  - Dihydrotestosterone as a Protective Agent in Chronic Experimental Autoimmune
      Encephalomyelitis.
AB  - Multiple sclerosis is a chronic inflammatory disease affecting the central
      nervous system. As reported by clinical observations, variation in hormonal
      levels might alter disease susceptibility and progression. Specifically,
      decreased levels of testosterone in males are reported to be permissive for
      disease onset. Accordingly, testosterone seems to exert protective effects in
      experimental autoimmune encephalomyelitis (EAE). In this context, it is important
      to highlight that testosterone is further metabolized into 17beta-estradiol or
      dihydrotestosterone (DHT). In this study, we aimed to explore the protective
      effects of DHT treatment in EAE Dark Agouti rats (i.e. an experimental model
      showing a protracted relapsing EAE). Data obtained 45 days after EAE induction
      showed that DHT exerts a beneficial effect on clinical scores, coupled with
      decreased gliosis (i.e. glial fibrillary acidic protein and major
      histocompatibility complex of class II staining) and inflammation (i.e.
      translocator protein 18 kDa, interleukin-1beta, Toll-like receptor 4 and nuclear
      factor-kappaB expression) in the spinal cord. Moreover, parameters linked to
      oxidative stress and tissue damage, like thiobarbituric acid-reactive substance
      levels and Bcl-2-associated X protein expression, and to mitochondrial activity
      (i.e. content of mitochondrial DNA and proteins), were improved after DHT
      administration. This neuroactive steroid may be further metabolized into 3alpha-
      or 3beta-diol. However, assessment of the levels of these metabolites after DHT
      treatment seems to suggest that the protective effects observed here are due to
      DHT itself. Altogether, the present results indicate that DHT was effective in
      reducing the severity of chronic EAE and, consequently, may represent an
      interesting perspective for multiple sclerosis treatment.

PMID- 25765437
TI  - Usage of psychiatric emergency services by asylum seekers: Clinical implications
      based on a descriptive study in Denmark.
AB  - BACKGROUND: Asylum seekers are found to be at high risk of mental health
      problems. Little is known about the use of acute psychiatric emergency services
      by asylum seekers. AIM: To describe the usage of an inpatient/outpatient
      psychiatric emergency service in Denmark by adult asylum seekers, and discuss
      clinical implications. METHOD: This descriptive study is based on retrospective
      data collected from patient charts during a 3-month period. RESULTS: A total of
      31 evaluations were made (3.3% of all evaluations), based on 23 asylum seekers.
      Patients originated from 16 different countries, were predominantly male and
      married. The group consisted primarily (61%) of failed asylum seekers. Most
      patients (81%) presented with relevant mental health problems. The main reasons
      for presenting to the acute psychiatric emergency service were suicidal ideation
      and/or behaviour (60%). The most frequent diagnosis given at the initial
      evaluation was ICD-10 F43.9 "reaction to severe stress, unspecified" (50%).
      Evaluations were made primarily by non-psychiatrists. No standardized screening
      or diagnostic instrument was used. CONCLUSION: This first description of the use
      of an acute psychiatric emergency service by asylum seekers in Denmark shows some
      of the acute mental health needs asylum seekers present with. The findings of
      high levels of suicidal ideation and possible diagnostic difficulties are
      discussed, as well as possible improvements of the referral and psychiatric
      evaluation processes.

PMID- 25765438
TI  - Effects of comorbid anxiety disorders on the course of bipolar disorder-I.
AB  - BACKGROUND AND AIMS: Although comorbid anxiety disorders (AD) are quite frequent
      in bipolar disorders (BD), data on how this comorbidity affects BD are limited.
      In the present study, we aimed to investigate the frequency of comorbid AD in
      Turkish patients with bipolar disorder-I (BD-I) and the effects of comorbid AD on
      the course of BD-I. METHODS: 114 patients with BD-I were included in the study.
      All patients were diagnosed by a psychiatrist. The patients were divided into two
      groups as BD-I patients with lifetime comorbid AD (BDI-CAD) or those without
      comorbid AD (BDI). RESULTS: 37 (32.46%) patients had one or more comorbid
      lifetime AD. The numbers of admissions to the outpatient clinic within calendar
      year 2013 (P = 0.014), the number of lifetime mood episodes (P = 0.019) and the
      duration of BD (P = 0.007) were higher in the BDI-CAD group compared with the BDI
      group. There was a strong relationship between the duration of the disorder and
      the number of episodes (r = 0.583, P < 0.001). Partial correlation analyses
      showed that the number of admission to the outpatient clinic correlated
      significantly with the frequency of episodes (P = 0.007, r = 0.282). CONCLUSION:
      We found that the patients with BDI-CAD use the healthcare system more frequently
      than the BDI patients. This suggests that AD comorbidity may have a negative
      influence on the course of BD-I and it is a factor that should be considered in
      the clinical follow-up.

PMID- 25765439
TI  - Is dental caries experience increased in HIV-infected children and adolescents? A
      meta-analysis.
AB  - OBJECTIVE: To undertake a systematic review to assess if HIV-infected children
      and adolescents have an increased dental caries experience. METHODS: A search of
      MEDLINE, BIREME, EMBASE, GOOGLE SCHOLAR, SIGLE (Grey Literature) and reference
      lists of included studies was carried out. To be eligible the studies had to
      present HIV-infected and non-infected children/adolescents between 0-18 years
      old. To assess the methodological quality, the studies were categorized in scores
      from 'A' to 'C'. To perform a meta-analysis a random effect model was used with
      95% confidence intervals and two distinct sub-group analyses were carried out in
      terms of caries progression: data for cavitated and non-cavitated lesions (sub
      group 1) and data only for cavitated lesions (sub-group 2). RESULTS: Five studies
      fulfilled the selection criteria. Four studies (two ranked A and two B in the
      quality assessment) revealed higher caries scores in primary teeth in the HIV
      infected patients with mean dmft/dmfs scores of 3.8-4.1/7.8-11.0 compared to the
      control group 1.5-2.4/3.4-5.1. No differences in caries index were found for
      permanent dentition. The meta-analysis excluded caries data of permanent teeth
      and showed a significant association between caries experience in primary
      dentition and HIV infection considering cavitated and non-cavitated lesions (OR =
      2.33, 95% CI = 1.48-3.68) or only cavitated lesions (OR = 2.98, 95% CI = 1.59
      5.59). CONCLUSION: Evidence exists that suggests HIV-infected
      children/adolescents have an increased caries experience in primary dentition.

PMID- 25765440
TI  - Mindfulness and personal identity in the Western cultural context: A plea for
      greater cosmopolitanism.
AB  - In the psychological sciences, mindfulness practices are increasingly being used,
      studied, and theorized, but their indigenous theoretical foundations in Buddhist
      accounts of the dynamics and psychology of personal identity tend to be
      overlooked. This situation is mirrored in the discipline of philosophy: here,
      Buddhist views on personal identity are beginning to draw attention, but almost
      invariably in a way which entirely blanks out the role of mindfulness practices
      in cultivating Buddhist insights on selfhood. The aggregate result is a failure,
      in the West, to reflect upon and seriously consider Buddhist theory and Buddhist
      practice in an integrated, holistic fashion. In its effort to overcome the
      compartmentalization of Buddhist theory (in philosophy) versus Buddhist practice
      (in psychology) and to embrace the challenges this might pose to fundamental
      Western beliefs about the self, this paper is intended both as a plea for and an
      exercise in greater, more venturesome cosmopolitanism. 

PMID- 25765441
TI  - In vivo visualization of honeycomb pattern, cobblestone pattern, ringed pattern,
      and dermal papillae by confocal laser scanning microscopy.
AB  - BACKGROUND: In vivo confocal laser scanning microscopy (CLSM) represents a
      promising technique for noninvasive visualization of lesions. Honeycomb pattern,
      cobblestone pattern, ringed pattern and dermal papillae are terms commonly used
      to describe CLSM architectures. Understanding of these four terms individually or
      in combination on confocal images facilitates the diagnosis and differential
      diagnosis of skin diseases. METHODS: Seventy-eight patients and 5 healthy
      controls were enrolled in the study. Their lesions were imaged with the VivaScope
      1500 reflectance confocal microscope. RESULTS: Concerning these four terms
      mentioned above, they had different features in different skin diseases and
      played an important role in the understanding of skin diseases individually or in
      combination. CONCLUSION: By understanding the CLSM features of honeycomb pattern,
      cobblestone pattern, ringed pattern and dermal papillae individually or in
      combination, the findings support the roles of these characteristic architectures
      in diagnosis and differential diagnosis of skin diseases.

PMID- 25765442
TI  - Global health care use by patients with type-2 diabetes: Does the type of
      comorbidity matter?
AB  - AIM: To identify patterns of health care use among diabetic patients with
      multimorbidity across primary, specialised, hospital and emergency care,
      depending on their type of chronic comorbidity. METHODS: Longitudinal study of a
      population-based retrospective cohort conformed by adult patients with type-2
      diabetes assigned to any of the primary care centres in Aragon during 2010 and
      2011 (n=65,716). Negative binomial regressions were run to model the effect of
      the type of comorbidity on the number of visits to each level of care.
      Comorbidities were classified as concordant, discordant or mental based on expert
      consensus and depending on whether they shared the same overall pathophysiologic
      risk profile and disease management plan designed for type-2 diabetes. RESULTS:
      Mental comorbidity was independently associated with total and unplanned
      admissions (incidence rate ratio [IRR]:1.25; 95% confidence interval [CI]:1.12
      1.39, IRR:1.21; 95% CI:1.06-1.39), average length of stay (IRR:1.47; 95% CI:1.25
      1.73), and total and priority emergency room visits (IRR:1.26; 95% CI:1.17-1.35,
      IRR:1.30; 95% CI:1.18-1.42). Patients with discordant comorbidities showed the
      strongest associations with the number of visits to specialists (IRR:1.38; 95%
      CI:1.33-1.43) and to different specialties (IRR:1.36; 95% CI:1.32-1.39).
      Differences regarding GP visits were lower but still significant for patients
      with discordant comorbidity (IRR:1.08; 95% CI:1.06-1.11), but especially for
      those with mental comorbidity (IRR:1.17; 95% CI:1.14-1.21). CONCLUSION: In
      patients with type-2 diabetes, the coexistence of mental comorbidity
      significantly increases the use of unplanned hospital services, and discordant
      comorbidities have an important effect on specialised care use. Differences with
      respect to primary care use are not as prominent.

PMID- 25765443
TI  - Iohexol transmembrane clearance during modeled continuous renal replacement
      therapy.
AB  - BACKGROUND/AIMS: Urea clearance during continuous renal replacement therapy
      (CRRT) is not representative of middle molecular weight solute clearances. We
      aimed to characterize iohexol, molecular weight 821 Da, clearance during
      continuous hemofiltration (CH) and continuous hemodialysis (CHD). METHODS: Using
      an in vitro model, iohexol sieving coefficients (SC) and saturation coefficients
      (SA) were determined with the M100 membrane at ultrafiltration/dialysate rates of
      1, 2, 3, 4, and 6 l/h. Iohexol transmembrane clearance was calculated using the
      measured SC and SA. RESULTS: During CH, the value of iohexol SC remained
      approximately 1 at all ultrafiltration rates studied. In contrast, during CHD
      iohexol the mean SA was 1.02 +/- 0.05 at a dialysate rate 1 l/h and decreased
      significantly with higher dialysate rates to a mean SA of 0.57 +/- 0.12 at a
      dialysate rate of 6 l/h. CONCLUSIONS: At higher effluent flow rates, CH was more
      effective in removing iohexol than CHD. CH transmembrane clearance of iohexol
      appears to approximate the ultrafiltration rate.

PMID- 25765444
TI  - Skin tumour surgery in primary care: do general practitioners need to improve
      their surgical skills?
AB  - BACKGROUND: Due to a rapid increase in the incidence of skin cancer, it seems
      inevitable that general practitioners (GPs) will play a larger role in skin
      cancer care. OBJECTIVES: To assess surgical procedures used by GPs in skin tumour
      management. METHODS: We performed a retrospective study of 1,898 pathology
      reports of skin tumours excised by GPs in 2009. RESULTS: In 22.9% no diagnosis
      was provided on the application form. Mostly, once-off excisions (no preceding
      biopsy) were performed, 7% of the excised lesions were malignant, and 35% of
      incisions were incomplete. Excisions in the face and neck region were incomplete
      in 65.4%; 22% of melanomas were biopsied or shaved. CONCLUSION: This study
      underlines the difficulties in skin tumour management in primary care. To
      stimulate adequate resource use, the number of excisions of benign lesions could
      be lowered, and pretreatment biopsy in non-melanoma skin cancer management should
      be encouraged. GPs should be aware of their limitations and consider referral of
      high-risk malignancies.

PMID- 25765445
TI  - Olfactory-ensheathing cell transplantation for peripheral nerve repair: update on
      recent developments.
AB  - A number of important advances have been made using transplantation of olfactory
      ensheathing cells (OECs) to provide therapeutic effects with regard to peripheral
      nerve repair. In vivo studies have focused on transplanting OECs to stimulate
      axonal regeneration and sprouting, increase remyelination, confer
      neuroprotection, enhance neovascularization and replace lost cells. OECs support
      axonal regeneration and remyelination with appropriate formation of axonal nodes
      of Ranvier with improvement of nerve conduction velocity. Current work using gene
      profiling and proteomics is identifying potential therapeutic differences between
      OECs harvested from nasal mucosa and the olfactory bulb and genes that OECs
      express that may be conducive to neural repair. OECs derived from nasal mucosa
      are of clinical interest since the cells could potentially be harvested from a
      patient and used for autotransplantation. Various nerve scaffolds and materials
      have been used for nerve repair and recent studies have examined OECs in
      combination with various supportive materials, including nanoparticles and
      scaffolds for peripheral nerve substance defects. This review will discuss the
      use of OECs in nerve repair and nerve defect injuries with specific emphasis on
      differences between OECs derived from the olfactory bulb and the olfactory
      mucosa.

PMID- 25765446
TI  - Three novel pathogenic mutations in KATP channel genes and somatic imprinting
      alterations of the 11p15 region in pancreatic tissue in patients with congenital
      hyperinsulinism.
AB  - BACKGROUND/AIMS: This study was performed to investigate the molecular pathology
      underlying focal and diffuse congenital hyperinsulinism (CHI). METHODS: The ABCC8
      and KCNJ11 genes were analyzed in 3 patients with focal CHI and in 1 patient with
      diffuse CHI. Immunohistochemistry, real-time PCR, methylation-specific multiplex
      ligation-dependent probe amplification (MS-MLPA) and microsatellite marker
      analyses of the 11p15 region were performed on both normal tissues and
      adenomatous hyperplasia lesions. RESULTS: The 3 patients with focal CHI harbored
      paternally inherited ABCC8 or KCNJ11 mutations. Compound heterozygous ABCC8
      mutations were identified in the patient with diffuse CHI. In the 3 patients with
      focal CHI, homozygous ABCC8 or KCNJ11 mutations were identified within the
      lesions. MLPA and real-time PCR revealed the presence of two copies of 11p15. MS
      MLPA and microsatellite analyses demonstrated abnormal imprinting patterns and
      focal loss of maternal 11p13-15 within the lesions. In contrast, parental
      heterozygosity was preserved in the normal tissue. In the patient with diffuse
      CHI, the two ABCC8 mutations were conserved, and imprinting patterns at 11p15
      were normal. CONCLUSIONS: The epigenetic alteration at the 11p15 region plays a
      central role in developing focal CHI by paternally derived mutations of the KATP
      channel and maternal allelic loss at this region. MS-MLPA and microsatellite
      analyses are useful to investigate the molecular etiology of CHI.

PMID- 25765447
TI  - [Nutritional status, nutritional self-perception, and use of licit drugs in
      adolescents].
AB  - OBJECTIVE: To associate the nutritional status and the self-perception of
      nutritional status with the use of licit drugs among adolescents. METHODS: Cross
      sectional study in which 210 adolescents answered a questionnaire on alcohol and
      tobacco experimentation and self-perceptions about their nutritional status. The
      correspondence between the adolescents' perception of their own nutritional
      status and actual nutritional status was analyzed, as well as associations
      between nutritional status, self-perception of nutritional status, gender, age,
      and presence of smokers at home with alcohol and tobacco use. The variables were
      analyzed separately in a bivariate analysis and, subsequently, a multivariate
      analysis determined the factors associated with drug use. RESULTS: The study
      included 210 adolescents with a median age of 148 months; 56.6% were females. Of
      the total sample, 6.6% have tried cigarettes, and 20% have tried alcohol; 32.3%
      had BMI Z-Score>=1, 12.85% had BMI Z-Score>=2, and 50.7% had a correct perception
      of his/her weight. After a multivariate analysis, only the self-perception about
      weight statistically influenced experimentation of tobacco, and patients who
      identified themselves as having very high weight were more likely to experiment
      tobacco (odds ratio (OR) 13.57; confidence interval (95% CI) 2.05-89.8; p=0.007);
      regarding alcohol use, adolescents who identified themselves as having high
      weight were 2.4 times more likely to experiment with alcohol than adolescents
      that identified themselves as having normal weight (95% CI 1.08-5.32, p=0.031).
      CONCLUSIONS: Adolescents with self-perception of excess weight may constitute a
      risk group for alcohol and tobacco use.

PMID- 25765448
TI  - [Turner syndrome and genetic polymorphism: a systematic review].
AB  - OBJECTIVE: To present the main results of the literature on genetic polymorphisms
      in Turner Syndrome and their association with the clinical signs and the etiology
      of this chromosomal disorder. DATA SOURCE: The review was conducted in the PubMed
      database without any time limit, using the terms Turner syndrome and genetic
      polymorphism. A total of 116 articles were found, and based on the established
      inclusion and exclusion criteria 17 were selected for the review. DATA SYNTHESIS:
      The polymorphisms investigated in patients with Turner Syndrome were associated
      with growth deficit, causing short stature, low bone mineral density,
      autoimmunity and cardiac abnormalities, which are frequently found in patients
      with Turner Syndrome. The role of single nucleotide polymorphisms (SNPs) in the
      etiology of Turner syndrome, i.e., in chromosomal nondisjunction, was also
      confirmed. CONCLUSIONS: Genetic polymorphisms appear to be associated with Turner
      Syndrome. However, in view of the small number of published studies and their
      contradictory findings, further studies in different populations are needed in
      order to clarify the role of genetic variants in the clinical signs and etiology
      of the Turner Syndrome.

PMID- 25765450
TI  - Mandala networks: ultra-small-world and highly sparse graphs.
AB  - The increasing demands in security and reliability of infrastructures call for
      the optimal design of their embedded complex networks topologies. The following
      question then arises: what is the optimal layout to fulfill best all the demands?
      Here we present a general solution for this problem with scale-free networks,
      like the Internet and airline networks. Precisely, we disclose a way to
      systematically construct networks which are robust against random failures.
      Furthermore, as the size of the network increases, its shortest path becomes
      asymptotically invariant and the density of links goes to zero, making it ultra
      small world and highly sparse, respectively. The first property is ideal for
      communication and navigation purposes, while the second is interesting
      economically. Finally, we show that some simple changes on the original network
      formulation can lead to an improved topology against malicious attacks. 

PMID- 25765449
TI  - Comparative transcriptome profiling of a rice line carrying Xa39 and its parents
      triggered by Xanthomonas oryzae pv. oryzae provides novel insights into the broad
      spectrum hypersensitive response.
AB  - BACKGROUND: Bacterial blight, caused by Xanthomonas oryzae pv. oryzae (Xoo), is a
      devastating rice disease worldwide. Xa39 is a resistance (R) gene with a broad
      spectrum hypersensitive response (BSHR) to Xoo. Nevertheless, the molecular
      mechanisms of resistance mediated by Xa39 remain unclear. In this study, the
      transcriptome profiling of a rice line carrying Xa39 and its parents at the early
      stage of Xoo infection were investigated. RESULTS: A rice introgression line H471
      carrying Xa39 exhibited a typical local hypersensitive response phenotype,
      accompanied by programmed cell death after inoculation with the Xoo Philippines'
      race 9b. Transcriptome profiling of H471 and its parents at 1 and 2 days post
      inoculation was performed using RNA sequencing. In total, 306 differentially
      expressed genes (DEGs) were identified in H471 compared with its recurrent parent
      Huang-Hua-Zhan after inoculation with Xoo. Among them, 121 (39.5%) genes, with
      functional enrichments that were related to defense response, protein amino acid
      phosphorylation, and apoptosis, were found to be constitutively expressed. The
      other 185 (60.5%) genes, with GO terms that belonged to defense response, were
      significantly responsive to Xoo infection in H471. Ten up-regulated and 12 down
      regulated genes encoding intracellular immune receptors were identified in H471
      compared with Huang-Hua-Zhan. LOC_Os11g37759, which was located in the fine
      mapping region harboring Xa39, is a Xa39 candidate gene. The putative BSHR
      related co-regulatory networks were constructed using 33 DEGs from four
      functional groups, including gibberellic acid receptors and brassinosteroid
      regulators, which were differentially co-expressed with LOC_Os11g37759 in
      infected H471. Our results indicated that there might be cross-talk between the
      Xa39-mediated signal transduction cascades and the GA/BR signaling pathway, and
      that the defense mechanism was related to diverse kinases, transcription factors,
      post-translational regulation, and R genes. CONCLUSIONS: The present study
      provides the comprehensive transcriptome profile of a rice introgression line
      carrying Xa39 and its parents, and identifies a set of DEGs involved in BSHR
      mediated by Xa39. These data provide novel insights into the regulatory networks
      of plant disease resistance mediated by R genes, and the identified DEGs will
      serve as candidates for Xa39 cloning and for further understanding the molecular
      mechanism of BSHR.

PMID- 25765451
TI  - Canadian administrative health data can identify patients with myasthenia gravis.
AB  - INTRODUCTION: Incidence and prevalence estimates for myasthenia gravis (MG) have
      varied widely, and the ability of administrative health data (AHD) records to
      accurately identify cases of MG is yet to be ascertained. The goal of the current
      study was to validate an algorithm to identify patients with MG in Ontario,
      Canada using AHD - thereby enabling future disease surveillance. METHODS: A
      reference standard population was established using automated key word searching
      within EMRALD (Electronic Medical Record Administrative data Linked Database) and
      chart review of potential cases. AHD algorithms were generated and tested against
      the reference standard. The data was used to calculate MG prevalence rates.
      RESULTS: There were 123,997 eligible adult patients, and 49 patients had definite
      MG (forming the reference standard). An algorithm requiring: (1 hospital
      discharge abstract with MG listed as a reason for hospitalization or a comorbid
      condition), or (5 outpatient MG visits and 1 relevant diagnostic test, within 1
      year), or (3 pyridostigmine prescriptions, within 1 year) identified MG with
      sensitivity = 81.6%, specificity = 100%, positive predictive value = 80.0% and
      negative predictive value = 100%. The population prevalence within our cohort was
      0.04%. CONCLUSIONS: This novel validation method demonstrates the feasibility of
      using administrative health data to identify patients with myasthenia gravis
      among the Ontario population.

PMID- 25765452
TI  - Left main coronary artery disease: importance, diagnosis, assessment and
      management. Foreword.

PMID- 25765453
TI  - Left main coronary artery disease: importance, diagnosis, assessment, and
      management.
AB  - Left main coronary disease is seen in 4%-6% of patients undergoing coronary
      angiography for an ischemic evaluation and is a potentially fatal condition if
      not promptly identified and treated. Recent studies have increased our
      understanding of the complexity of left main coronary artery disease. This lesion
      subset offers numerous challenges in diagnosis and management. Fractional flow
      reserve and intravascular ultrasound are important adjuncts to angiography to
      determine the significance of ambiguous lesions of the left main coronary artery.
      Surgery is associated with much better outcomes than medical therapy and is
      considered by many to be the standard of care in patients who are surgical
      candidates. Recent studies comparing surgery with percutaneous coronary
      intervention (PCI) have defined subgroups with lesser extent of disease burden
      that may do just as well with PCI. Challenges remain in the management of
      bifurcation disease, and the interventional community anxiously awaits the
      results of the large-scale randomized trials comparing PCI with surgery. 

PMID- 25765454
TI  - Distributed ultrafast fibre laser.
AB  - A traditional ultrafast fibre laser has a constant cavity length that is
      independent of the pulse wavelength. The investigation of distributed ultrafast
      (DUF) lasers is conceptually and technically challenging and of great interest
      because the laser cavity length and fundamental cavity frequency are changeable
      based on the wavelength. Here, we propose and demonstrate a DUF fibre laser based
      on a linearly chirped fibre Bragg grating, where the total cavity length is
      linearly changeable as a function of the pulse wavelength. The spectral sidebands
      in DUF lasers are enhanced greatly, including the continuous-wave (CW) and pulse
      components. We observe that all sidebands of the pulse experience the same round
      trip time although they have different round-trip distances and refractive
      indices. The pulse-shaping of the DUF laser is dominated by the dissipative
      processes in addition to the phase modulations, which makes our ultrafast laser
      simple and stable. This laser provides a simple, stable, low-cost, ultrafast
      pulsed source with controllable and changeable cavity frequency. 

PMID- 25765455
TI  - Distribution of islet hormones in human adult pancreatic ducts.
AB  - BACKGROUND/AIMS: The source of insulin-secreting cells from adult duct system is
      attractive, but its clinical practice remains poorly understood. Here, we aimed
      at identifying the distribution of secreted hormone reactive cells in adult
      ducts. METHODS: Consecutive pancreatic slices from nondiabetic subjects were
      subjected to immunohistochemistry and immunofluorescence to screen islet hormones
      (insulin; glucagon, Glu; somatostatin, Som; pancreatic polypeptide, PP) and
      exocrine biomarkers (cytokeratin 19, CK19; chromogranin A, CgA; amylase). All
      pancreatic sections were imaged using an optical or confocal microscope. RESULTS:
      Immunostaining results showed that insulin was expressed in adult ducts, in which
      the cell count was more than other islet hormone immunoactive cells. CK19
      positive cells are mainly distributed in the ducts, whereas CgA-labeled cells are
      localized in endocrine cells. The duct branches visibly exhibited cell
      populations that co-expressed islet hormones in exocrine cell populations.
      CONCLUSIONS: In this report, our findings demonstrate that adult ductal cells
      that produce insulin may contribute to beta-cell proliferation.

PMID- 25765456
TI  - Increased treatment durations lead to greater improvements in non-weight bearing
      dorsiflexion range of motion for asymptomatic individuals immediately following
      an anteroposterior grade IV mobilisation of the talus.
AB  - Manual therapy aims to minimise pain and restore joint mobility and function.
      Joint mobilisations are integral to these techniques, with anteroposterior (AP)
      talocrural joint mobilisations purported to increase dorsiflexion range of motion
      (DF-ROM). This study aimed to determine whether different treatment durations of
      single grade IV anteroposterior talocrural joint mobilisations elicit
      statistically significant differences in DF-ROM. Sixteen asymptomatic male
      football players (age = 27.1 +/- 5.3 years) participated in the study. Non-weight
      bearing (NWB) and weight bearing (WB) DF-ROM was measured before and after 4
      randomised treatment conditions: control treatment, 30 s, 1 min, 2 min. NWB DF
      ROM was measured using a universal goniometer, and WB DF-ROM using the weight
      bearing lunge test. A within-subjects design was employed so that all
      participants received each of the treatment conditions. A 4 * 4 balanced Latin
      square design and 1 week interval between sessions reduced any residual effects.
      Two-way repeated measures ANOVA revealed a significant improvement in DF-ROM
      following all AP mobilisation treatments (p < 0.001). The within subjects
      contrasts showed that increases in treatment duration was associated with
      statistically significant improvements in DF-ROM (NWB DF-ROM control = 0.01%, 30
      s = 14.2%, 1 min = 21.6%, 2 min = 32.8%; WB DF-ROM control = 0.01%, 30 s = 5.0%,
      1 min = 7.6%, 2 min = 10.9%; p < 0.05). However, WB DF-ROM improvements were
      below the minimal detectable change scores needed to conclude that improvements
      were not a consequence of measurement error. This research shows that single
      session mobilisations can elicit NWB DF-ROM improvements in asymptomatic
      individuals in the absence of pain, whilst increases in treatment duration confer
      greater improvements in NWB DF-ROM within this population.

PMID- 25765458
TI  - Fragment size does not matter when you are well connected: effects of
      fragmentation on fitness of coexisting gypsophiles.
AB  - Most habitat fragmentation studies have focused on the effects of population size
      on reproductive success of single species, but studies assessing the effects of
      both fragment size and connectivity, and their interaction, on several coexisting
      species are rare. In this study, we selected 20 fragments along two continuous
      gradients of size and degree of isolation in a gypsum landscape in central Spain.
      In each fragment, we selected 15 individuals of each of three dominant
      gypsophiles (Centaurea hyssopifolia, Lepidium subulatum and Helianthemum
      squamatum, 300 plants per species, 900 plants in total) and measured several
      reproductive traits: inflorescence number, fruit set, seed set and seed mass. We
      hypothesised that plant fitness would be lower on small and isolated fragments
      due to an interaction between fragment size and connectivity, and that response
      patterns would be species-specific. Overall, fragment size had very little effect
      on reproductive traits compared to that of connectivity. We observed a positive
      effect of fragment connectivity on C. hyssopifolia fitness, mediated by the
      increased seed predation in plants from isolated fragments, resulting in fewer
      viable seeds per capitulum and lower seed set. Furthermore, seed mass was lower
      in plants from isolated fragments for both C. hyssopifolia and L. subulatum. In
      contrast, few reproductive traits of H. squamatum were affected by habitat
      fragmentation. We discuss the implications of species-specific responses to
      habitat fragmentation for the dynamics and conservation of gypsum plant
      communities. Our results highlight the complex interplay among plants and their
      mutualistic and antagonistic visitors, and reinforce the often-neglected role of
      habitat connectivity as a key component of the fragmentation process. 

PMID- 25765457
TI  - Pharmacotherapy for recurrent ovarian cancer: current status and future
      perspectives.
AB  - Several 'lines of therapy' that utilize cytotoxic agents and are driven by
      platinum-free intervals are the current standard of care for patients with
      recurrent ovarian cancer. For patients with platinum-resistant disease, single
      agent chemotherapy (pegylated liposomal doxorubicin, topotecan, gemcitabine or
      weekly paclitaxel) is the standard of care. For patients with platinum-sensitive
      disease, combination chemotherapy (carboplatin plus paclitaxel, pegylated
      liposomal doxorubicin or gemcitabine) is the standard of care. In addition,
      antiangiogenic therapy using bevacizumab is an established option. Future
      directions could include 'lines of therapy' with biologic agents driven by
      specific biologic targets. Data from antiangiogenic agents (trebananib, pazopanib
      and cediranib), antifolate drugs (farletuzumab and vintafolide), poly(ADP-ribose)
      polymerase inhibitors (olaparib and veliparib), mTOR inhibitors (everolimus and
      temsirolimus) and immune editing agents (nivolumab) have been summarized in this
      review. 

PMID- 25765459
TI  - Urban contamination sources reflected in inorganic pollution in urban lake
      deposits, Bergen, Norway.
AB  - The 7000 years transition from a pristine environment towards a modern city has
      brought a number of chemical changes and effects to urban lake sediments in
      Bergen. Metals, such as Pb, Hg, Zn, Cu and Fe, display a large anthropogenic
      influence and reflect historical point sources that existed within the drainage
      area from approximately AD 1790 until today. The concentration peaks alternate
      with intervals of lower concentration due to phases of coarser grained sediment
      input but also periods of potentially reduced metal influx. All discussed
      elements, except Cd, increase in concentration with decreasing grain size and
      also correlate with the amount of clay fraction particles. The results emphasize
      the importance of considering grain size when interpreting sediment chemistry.
      Correlation with TOC is not apparent in the same extent. The transition from
      natural to anthropogenically influenced sediments, which is characterised by a
      sudden increase of several elements, is accompanied by a reduction in Cd, As and
      Ni concentration. This is interpreted to be the result of hypoxia, changes in pH
      and reduced erosional input. Factor analysis and the comparison with reference
      sediments indicate that the elements Pb, Hg, Zn and Cu most clearly demonstrate
      man-made pollution. Analyses of stormwater culvert sediments suggest that urban
      runoff contributes to the pollution load today, with standing building mass and
      traffic contributing to the load. 

PMID- 25765460
TI  - Comparative genome analysis of Prevotella intermedia strain isolated from
      infected root canal reveals features related to pathogenicity and adaptation.
AB  - BACKGROUND: Many species of the genus Prevotella are pathogens that cause oral
      diseases. Prevotella intermedia is known to cause various oral disorders e.g.
      periodontal disease, periapical periodontitis and noma as well as colonize in the
      respiratory tract and be associated with cystic fibrosis and chronic bronchitis.
      It is of clinical significance to identify the main drive of its various
      adaptation and pathogenicity. In order to explore the intra-species genetic
      differences among strains of Prevotella intermedia of different niches, we
      isolated a strain Prevotella intermedia ZT from the infected root canal of a
      Chinese patient with periapical periodontitis and gained a draft genome sequence.
      We annotated the genome and compared it with the genomes of other taxa in the
      genus Prevotella. RESULTS: The raw data set, consisting of approximately 65X
      coverage reads, was trimmed and assembled into contigs from which 2165 ORFs were
      predicted. The comparison of the Prevotella intermedia ZT genome sequence with
      the published genome sequence of Prevotella intermedia 17 and Prevotella
      intermedia ATCC25611 revealed that ~14% of the genes were strain-specific. The
      Preveotella intermedia strains share a set of conserved genes contributing to its
      adaptation and pathogenic and possess strain-specific genes especially those
      involved in adhesion and secreting bacteriocin. The Prevotella intermedia ZT
      shares similar gene content with other taxa of genus Prevotella. The genomes of
      the genus Prevotella is highly dynamic with relative conserved parts: on average,
      about half of the genes in one Prevotella genome were not included in another
      genome of the different Prevotella species. The degree of conservation varied
      with different pathways: the ability of amino acid biosynthesis varied greatly
      with species but the pathway of cell wall components biosynthesis were nearly
      constant. Phylogenetic tree shows that the taxa from different niches are
      scarcely distributed among clades. CONCLUSIONS: Prevotella intermedia ZT belongs
      to a genus marked with highly dynamic genomes. The specific genes of Prevotella
      intermedia indicate that adhesion, competing with surrounding microbes and
      horizontal gene transfer are the main drive of the evolution of Prevotella
      intermedia.

PMID- 25765463
TI  - Severe self-injurious behavior with teeth extraction in a boy with Tourette
      syndrome.

PMID- 25765461
TI  - Diagnostic accuracy study of anorectal manometry for diagnosis of dyssynergic
      defecation.
AB  - OBJECTIVE: The diagnostic accuracy of anorectal manometry (AM), which is
      necessary to diagnose functional defecatory disorders (FDD), is unknown. Using
      blinded analysis and standardised reporting of diagnostic accuracy, we evaluated
      whether AM could discriminate between asymptomatic controls and patients with
      functional constipation (FC). DESIGN: Derived line plots of anorectal pressure
      profiles during simulated defecation were independently analysed in random order
      by three expert observers blinded to health status in 85 women with FC and 85 age
      matched asymptomatic healthy volunteers (HV). Using accepted criteria, these
      pressure profiles were characterised as normal (ie, increased rectal pressure
      coordinated with anal relaxation) or types I-IV dyssynergia. Interobserver
      agreement and diagnostic accuracy were determined. RESULTS: Blinded consensus
      based assessment disclosed a normal pattern in 16/170 (9%) of all participants
      and only 11/85 (13%) HV. The combined frequency of dyssynergic patterns (I-IV)
      was very similar in FC (80/85 (94%)) and HV (74/85 (87%)). Type I dyssynergia
      ('paradoxical' contraction) was less prevalent in FC (17/85 (20%) than in HV
      (31/85 (36.5%), p=0.03). After statistical correction, only type IV dyssynergia
      was moderately useful for discriminating between FC (39/85 (46%)) and HV (17/85
      (20%)) (p=0.001, positive predictive value=70.0%, positive likelihood ratio=2.3).
      Interobserver agreement was substantial or moderate for identifying a normal
      pattern, dyssynergia types I and IV, and FDD, and fair for types II and III.
      CONCLUSIONS: While the interpretation of AM patterns is reproducible, nearly 90%
      of HV have a pattern that is currently regarded as 'abnormal' by AM. Hence, AM is
      of limited utility for distinguishing between FC and HV.

PMID- 25765462
TI  - A mechanistic multicentre, parallel group, randomised placebo-controlled trial of
      mesalazine for the treatment of IBS with diarrhoea (IBS-D).
AB  - INTRODUCTION: Immune activation has been reported in the mucosa of IBS patients
      with diarrhoea (IBS-D), and some small studies have suggested that mesalazine may
      reduce symptoms. We performed a double-blind, randomised placebo-controlled trial
      of 2 g mesalazine twice daily versus placebo for 3 months in patients with Rome
      III criteria IBS-D. Primary outcome was daily average stool frequency during
      weeks 11-12; secondary outcomes were abdominal pain, stool consistency, urgency
      and satisfactory relief of IBS symptoms. METHODS: Participants were randomised
      after a 2-week baseline stool diary. All participants completed a 12-week stool
      diary and at the end of each week recorded the presence of 'satisfactory relief
      of IBS symptoms'. RESULTS: 136 patients with IBS-D (82 women, 54 men) were
      randomised, 10 patients withdrew from each group. Analysis by intention to treat
      showed the daily average stool frequency during weeks 11 and 12 were mean (SD),
      2.8 (1.2) in mesalazine and 2.7 (1.9) in the placebo group with no significant
      group difference, (95% CI) 0.1 (-0.33 to 0.53), p=0.66. Mesalazine did not
      improve abdominal pain, stool consistency nor percentage with satisfactory relief
      compared with placebo during the last two-weeks follow-up. CONCLUSIONS: This
      study does not support any clinically meaningful benefit or harm of mesalazine
      compared with placebo in unselected patients with IBS-D. More precise subtyping
      based on underlying disease mechanisms is needed to allow more effective
      targeting of treatment in IBS. TRIAL REGISTRATION NUMBER: NCT01316718.

PMID- 25765464
TI  - Primary microcephaly with anterior predominant pachygyria caused by novel
      compound heterozygous mutations in ASPM.

PMID- 25765465
TI  - Organocatalytic asymmetric Michael addition of 3-substituted oxindoles to
      alpha,beta-unsaturated acyl phosphonates for the synthesis of 3,3'-disubstituted
      oxindoles with chiral squaramides.
AB  - A highly enantioselective Michael addition of 3-monosubstituted oxindoles to
      alpha,beta-unsaturated acyl phosphonates with chiral squaramides as catalysts is
      investigated for the first time. A wide range of 3,3'-disubstituted oxindole
      adducts bearing adjacent quaternary and tertiary stereogenic centres could be
      smoothly obtained in good yields (up to 98%), diastereo- (up to >99 : 1 dr) and
      enantioselectivities (up to 98% ee) with the developed protocols. 

PMID- 25765467
TI  - In vitro Dermal Absorption: Sample Application and Seal Quality in a Franz
      Diffusion Cell System.
AB  - One of the known drawbacks of in vitro dermal absorption methods is their high
      interlaboratory variation. Although often attributed to biological skin
      differences, it has been shown that validation of other parameters such as
      temperature and stirring speed can reduce the high variability observed. The
      Organisation for Economic Co-operation and Development (OECD) and, at the EU
      level, the Scientific Committee on Consumer Safety (SCCS) have published guidance
      documents of how to perform these in vitro tests. For the parameter 'sample
      application' and 'adequate seal', it is indicated to apply the sample
      homogeneously and provide an adequate seal between the donor chamber and the
      membrane on which the sample is applied. Here, a simple and visual densitometer
      based method is provided, which makes evaluation possible of any application
      protocol used.

PMID- 25765466
TI  - Increased susceptibility to otitis media in a Splunc1-deficient mouse model.
AB  - Otitis media (inflammation of the middle ear) is one of the most common diseases
      of early childhood. Susceptibility to otitis is influenced by a number of
      factors, including the actions of innate immune molecules secreted by the
      epithelia lining the nasopharynx, middle ear and Eustachian tube. The SPLUNC1
      (short palate, lung, nasal epithelial clone 1) protein is a highly abundant
      secretory product of the mammalian nasal, oral and respiratory mucosa that is
      thought to play a multifunctional role in host defense. In this study we
      investigated Splunc1 expression in the ear of the mouse, and examined whether
      this protein contributes to overall host defense in the middle ear and/or
      Eustachian tube. We found that Splunc1 is highly expressed in both the surface
      epithelium and in submucosal glands in these regions in wild-type mice. In mice
      lacking Splunc1, we noted histologically an increased frequency of otitis media,
      characterized by the accumulation of leukocytes (neutrophils with scattered
      macrophages), proteinaceous fluid and mucus in the middle ear lumens.
      Furthermore, many of these mice had extensive remodeling of the middle ear wall,
      suggesting a chronic course of disease. From these observations, we conclude that
      loss of Splunc1 predisposes mice to the development of otitis media. The Splunc1(
      /-) mouse model should help investigators to better understand both the
      biological role of Splunc1 as well as host defense mechanisms in the middle ear. 

PMID- 25765468
TI  - Oxidative shielding and the cost of reproduction.
AB  - Life-history theory assumes that reproduction and lifespan are constrained by
      trade-offs which prevent their simultaneous increase. Recently, there has been
      considerable interest in the possibility that this cost of reproduction is
      mediated by oxidative stress. However, empirical tests of this theory have
      yielded equivocal support. We carried out a meta-analysis to examine associations
      between reproduction and oxidative damage across markers and tissues. We show
      that oxidative damage is positively associated with reproductive effort across
      females of various species. Yet paradoxically, categorical comparisons of
      breeders versus non-breeders reveal that transition to the reproductive state is
      associated with a step-change reduction in oxidative damage in certain tissues
      and markers. Developing offspring may be particularly sensitive to harm caused by
      oxidative damage in mothers. Therefore, such reductions could potentially
      function to shield reproducing mothers, gametes and developing offspring from
      oxidative insults that inevitably increase as a consequence of reproductive
      effort. According to this perspective, we hypothesise that the cost of
      reproduction is mediated by dual impacts of maternally-derived oxidative damage
      on mothers and offspring, and that mothers may be selected to diminish such
      damage. Such oxidative shielding may explain why many existing studies have
      concluded that reproduction has little or no oxidative cost. Future advance in
      life-history theory therefore needs to take account of potential
      transgenerational impacts of the mechanisms underlying life-history trade-offs. 

PMID- 25765469
TI  - Passerini/Tsuji-Trost strategies towards achieving lactams and cyclopentane
      derivatives.
AB  - The Passerini reaction of alpha,beta-unsaturated aldehydes affords suitable
      substrates for the Tsuji-Trost reaction with various carbon based-nucleophiles.
      The resulting alpha,beta-unsaturated amides may be cyclized to lactams or
      converted into cyclopentane derivatives if bis-nucleophiles are used in the Tsuji
      Trost step. 

PMID- 25765470
TI  - The effects of maternal depression, anxiety, and perceived stress during
      pregnancy on preterm birth: A systematic review.
AB  - BACKGROUND: Experiencing psychological distress such as depression, anxiety,
      and/or perceived stress during pregnancy may increase the risk for adverse birth
      outcomes, including preterm birth. Clarifying the association between exposure
      and outcome may improve the understanding of risk factors for prematurity and
      guide future clinical and research practices. AIM: The aims of the present review
      were to outline the evidence on the risk of preterm associated with antenatal
      depression, anxiety, and stress. METHODS: Four electronic database searches were
      conducted to identify quantitative population-based, multi-centre, cohort studies
      and randomised-controlled trial studies focusing on the association between
      antenatal depression, anxiety, and stress, and preterm birth published in English
      between 1980 and 2013. FINDINGS: Of 1469 electronically retrieved articles, 39
      peer-reviewed studies met the final selection criteria and were included in this
      review following the PRISMA and MOOSE review guidelines. Information was
      extracted on study characteristics; depression, anxiety and perceived stress were
      examined as separate and combined exposures. There is strong evidence that
      antenatal distress during the pregnancy increases the likelihood of preterm
      birth. CONCLUSION: Complex paths of significant interactions between depression,
      anxiety and stress, risk factors and preterm birth were indicated in both direct
      and indirect ways. The effects of pregnancy distress were associated with
      spontaneous but not with medically indicated preterm birth. Health practitioners
      engaged in providing perinatal care to women, such as obstetricians, midwives,
      nurses, and mental health specialists need to provide appropriate support to
      women experiencing psychological distress in order to improve outcomes for both
      mothers and infants.

PMID- 25765471
TI  - Impact of epidermal growth factor receptor protein and gene alteration on
      Taiwanese hepatocellular carcinomas.
AB  - BACKGROUND AND AIM: Epidermal growth factor receptor (EGFR) overexpression is
      associated with disease progression and poor survival in a variety of solid
      tumors. The role of EGFR in hepatocellular carcinoma (HCC) remains controversial.
      METHODS: One hundred thirty-eight HCCs were analyzed for total EGFR (t-EGFR) and
      phospho-EGFR (p-EGFR) expression and gene amplification using
      immunohistochemistry and fluorescence in situ hybridization. The role of EGFR was
      analyzed in relation to the clinicopathological features. RESULTS: Weak to strong
      p-EGFR immunostaining was noted in 42 of the 138 HCCs. p-EGFR expression
      correlated with alcoholism (P = 0.03) and chronic hepatitis B infection (P =
      0.041). There was no correlation between t-EGFR expression and any of the
      clinicopathological features. Amplification of the EGFR gene was not identified
      in the 138 HCCs, but 39.1% of the HCCs showed balanced polysomy of both the EGFR
      gene and centromere 7. Moreover, 65 tumors showed > 2.2 copies per tumor cell.
      EGFR copy number gain (CNG) was significantly correlated with gender (P =
      0.0491), tumor grade (P = 0.006), and vascular invasion (P = 0.005). HCCs with
      EGFR CNG also had a poor recurrence-free survival (RFS), as compared with HCCs
      without EGFR CNG (P = 0.031). When exploring the impact of gender, a significant
      association of EGFR CNG was found with tumor grade (P = 0.044) and cirrhosis (P =
      0.015) exclusively in the male group only; however, the OS and RFS analysis show
      no significant difference between male and female groups. CONCLUSIONS: EGFR CNG
      was related to crucial clinicopathological features and early recurrence,
      indicating that EGFR CNG might be a poor prognosis factor for Taiwanese HCC.

PMID- 25765472
TI  - Comprehensive analysis of desmosomal gene mutations in Han Chinese patients with
      arrhythmogenic right ventricular cardiomyopathy.
AB  - Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a cardiomyopathy that
      primarily involves the right ventricle. Mutations in desmosomal genes have been
      associated with ARVC. But its prevalence and spectrum are much less defined in
      the Chinese population, especially Han Chinese, a majority ethnic group in China;
      also the genotype-phenotype correlation regarding left ventricular involvement is
      still poorly understood. The aim of this study was to elucidate the genotype in
      Han Chinese patients with ARVC and the phenotype regarding cardiac left ventricle
      involvement in mutation carriers of ARVC. 48 Han Chinese patients were recruited
      into the present study based on the Original International Task Force Criteria of
      ARVC. Clinical data were reassessed according to the modified criteria published
      in 2010. A total of 36 subjects were diagnosed with ARVC; 12 patients were
      diagnosed with suspected ARVC. Five desmosomal genes (PKP2, DSG2, DSP, DSC2 and
      JUP) were sequenced directly from genomic DNA. Among the 36 patients, 21
      mutations, 12 of which novel, were discovered in 19 individuals (19 of 36, 53%).
      The distribution of the mutations was 25% in PKP2, 14% in DSP, 11% in DSG2, 6% in
      JUP, and 3% in DSC2. Multiple mutations were identified in 2 subjects (2 of 36,
      6%); both had digenic heterozygosity. Eight mutations, of which six were novel,
      were located in highly conserved regions. Seven mutations introduced a stop codon
      prematurely, which would result in premature termination of the protein
      synthesis. Two-dimensional echocardiography showed that LDVd and LDVs parameters
      were significantly larger in nonsense mutation carriers than in carriers of other
      mutations. In this comprehensive desmosome genetic analysis, 21 mutations were
      identified in five desmosomal genes in a group of 48 local Han Chinese subjects
      with ARVC, 12 of which were novel. PKP2 mutations were the most common variants.
      Left ventricular involvement could be a sign that the patient is a carrier of a
      nonsense cardiac desmosomal gene mutation. 

PMID- 25765473
TI  - The efficacy of balloon dilation in achalasia is the result of stretching of the
      lower esophageal sphincter, not muscular disruption.
AB  - Pneumatic dilation (PD) of the lower esophageal sphincter (LES) in achalasia is a
      major palliative treatment. It is generally believed, although never
      substantiated, that therapeutic efficacy of ballooning in achalasia is the result
      of the disruption and tearing of the muscular layers of the LES. To clarify this
      issue, we investigated the frequency of muscular disruption at the LES, 24 hours
      after PD, by employing the endoscopic ultrasound (EUS), in a group of 43
      consented patients with achalasia. Between July 2009 and March2012, 51
      consecutive adult patients with tentative diagnosis of achalasia, some with
      recurrence of symptoms after an earlier treatment with balloon dilation, were
      evaluated and underwent PD, using Rigiflex balloon without major adverse effect.
      Out of the 51 evaluated, 43 eligible and consenting patients who underwent EUS,
      24 hours after PD, using Olympus GF-UE 160 echoendoscope and an Aloka Prosound
      probe at 7.5 MHZ, are the subjects of this study. The EUS in 43 eligible patients
      revealed an intact LES in 36 (83.7%), small area of muscular disruption in 5
      (11.6%) and small hematoma in 2 patients (4.6%). Our data convincingly
      demonstrate that the clinical effectiveness of balloon dilation in achalasia is
      not the result of muscular disruption, but of circumferential stretching of the
      LES. Our findings on the mechanism of action of PD in achalasia could result in
      modifying the current method of dilation for a safer procedure, by slowing the
      rate of inflation and allowing the sphincter to slowly stretch itself to the
      distending balloon. 

PMID- 25765474
TI  - Steroid hormone related effects of marine persistent organic pollutants in human
      H295R adrenocortical carcinoma cells.
AB  - Persistent organic pollutants (POPs) such as 2,3,7,8-tetrachlorodibenzo-p-dioxin
      (TCDD), polychlorobiphenyl (PCB) 126 and 153, perfluorooctanesulfonic acid
      (PFOS), hexabromocyclododecane (HBCD), 2,2',4,4'-tetrabromodiphenyl ether (BDE
      47), tributyltin (TBT), and methylmercury (MeHg) can be accumulated in seafood
      and then form a main source for human exposure. Some POPs have been associated
      with changes in steroid hormone levels in both humans and animals. This study
      describes the in vitro effects of these POPs and mixtures thereof in H295R
      adrenocortical carcinoma cells. Relative responses for 13 steroid hormones and 7
      genes involved in the steroidogenic pathway, and CYP1A1, were analyzed. PFOS
      induced the most pronounced effects on steroid hormone levels by significantly
      affecting 9 out of 13 hormone levels measured, with the largest increases found
      for 17beta-estradiol, corticosterone, and cortisol. Furthermore, TCDD, both PCBs,
      and TBT significantly altered steroidogenesis. Increased steroid hormone levels
      were accompanied by related increased gene expression levels. The differently
      expressed genes were MC2R, CYP11B1, CYP11B2, and CYP19A1 and changes in gene
      expression levels were more sensitive than changes in hormone levels. The POP
      mixtures tested showed mostly additive effects, especially for DHEA and 17beta
      estradiol levels. This study shows that some seafood POPs are capable of altering
      steroidogenesis in H295R cells at concentrations that mixtures might reach in
      human blood, suggesting that adverse health effects cannot be excluded. 

PMID- 25765475
TI  - In vitro human metabolism of permethrin isomers alone or as a mixture and the
      formation of the major metabolites in cryopreserved primary hepatocytes.
AB  - In vitro metabolism of permethrin, a pyrethroid insecticide, was assessed in
      primary human hepatocytes. In vitro kinetic experiments were performed to
      estimate the Michaelis-Menten parameters and the clearances or formation rates of
      the permethrin isomers (cis- and trans-) and three metabolites, cis- and trans-3
      (2,2 dichlorovinyl)-2,2-dimethyl-(1-cyclopropane) carboxylic acid (cis- and trans
      DCCA) and 3-phenoxybenzoic acid (3-PBA). Non-specific binding and the activity of
      the enzymes involved in permethrin's metabolism (cytochromes P450 and
      carboxylesterases) were quantified. Trans-permethrin was cleared more rapidly
      than cis-permethrin with a 2.6-factor (25.7+/-0.6 and 10.1+/-0.3 MUL/min/10(6)
      cells respectively). A 3-factor was observed between the formation rates of DCCA
      and 3-PBA obtained from trans- and cis-permethrin. For both isomers, the rate of
      formation of DCCA was higher than the one of 3-PBA. The metabolism of the isomers
      in mixture was also quantified. The co-incubation of isomers at different ratios
      showed the low inhibitory potential of cis- and trans-permethrin on each other.
      The estimates of the clearances and the formation rates in the co-incubation
      condition did not differ from the estimates obtained with a separate incubation.
      These metabolic parameters may be integrated in physiologically based
      pharmacokinetic (PBPK) models to predict the fate of permethrin and metabolites
      in the human body.

PMID- 25765476
TI  - Characterization of in vitro metabolites of cudratricusxanthone A in human liver
      microsomes.
AB  - Cudratricusxanthone A (CTXA), isolated from the roots of Cudrania tricuspidata,
      exhibits several biological activities; however, metabolic biotransformation was
      not investigated. Therefore, metabolites of CTXA were investigated and the major
      metabolic enzymes engaged in human liver microsomes (HLMs) were characterized
      using liquid chromatography-tandem mass spectrometry (LC-MS/MS). CTXA was
      incubated with HLMs or human recombinant CYPs and UGTs, and analysed by an LC
      MS/MS equipped electrospray ionization (ESI) to qualify and quantify its
      metabolites. In total, eight metabolites were identified: M1-M4 were identified
      as mono-hydroxylated metabolites during Phase I, and M5-M8 were identified as O
      glucuronidated metabolites during Phase II in HLMs. Moreover, these metabolite
      structures and a metabolic pathway were identified by elucidation of MS(n)
      fragments and formation by human recombinant enzymes. M1 was formed by CYP2D6,
      and M2-M4 were generated by CYP1A2 and CYP3A4. M5-M8 were mainly formed by
      UGT1A1, respectively. While investigating the biotransformation of CTXA, eight
      metabolites of CTXA were identified by CYPs and UGTs; these data will be valuable
      for understanding the in vivo metabolism of CTXA.

PMID- 25765477
TI  - Blocking and bridging ligands direct the structure and magnetic properties of
      dimers of pentacoordinate nickel(II).
AB  - Dinuclear pentacoordinate nickel(ii) complexes of the formula [(NiTp*)2(MU-L)]
      (Tp* = hydrotris(3,5-dimethylpyrazolyl)borate; L = oxalate (); oxamate ();
      oxamidate (); OC(4-Cl-C6H4N)C(4-Cl-C6H4N)O ()) and {[Ni(N3-mc)]2(MU-L)}(PF6)2 (N3
      mc = 2,4,4-trimethyl-1,5,9-triazacyclododec-1-ene; L = oxalate (); oxamate ())
      have been synthesized and spectroscopically characterized (IR, (1)H NMR). X-ray
      structures of show nickel(ii) in a square pyramidal geometry and different
      supramolecular interactions. Magnetic measurements for show strong
      antiferromagnetic interactions across the bridging ligand [: J = -36.8 cm(-1), g
      = 2.16; : J = -43.6 cm(-1), g = 2.12; : J = -51.1 cm(-1), g = 2.12; : J = -39.7
      cm(-1), g = 2.18; : J = -35.4 cm(-1), g = 2.20; : J = -44.3 cm(-1), g = 2.18].
      Magneto-structural correlations between the magnitude of the magnetic coupling
      and the different blocking ligands, the different bridging ligands, the
      distortion of the coordination environment of Ni(ii) and the planarity between
      the bridging ligand and the basal plane of the Ni(ii) environment have been
      established for all complexes. 

PMID- 25765479
TI  - Hydrogen-bond-mediated aglycone delivery (HAD): a highly stereoselective
      synthesis of 1,2-cis alpha-D-glucosides from common glycosyl donors in the
      presence of bromine.
AB  - Described herein is the expansion of the picoloyl protecting-group assisted H
      bond mediated aglycone delivery (HAD) method recently introduced by our
      laboratory. At first it was noticed that high alpha-stereoselectivity is only
      obtained with S-ethyl glycosyl donors and only in the presence of
      dimethyl(methylthio)sulfonium trifluoromethanesulfonate (DMTST), in high
      dilution, and low temperature. Combining the mechanistic studies of the HAD
      reaction and bromine-promoted glycosylations allowed a very effective method to
      be devised that allows for highly stereoselective alpha-glycosidation of
      practically all common leaving groups (S-phenyl, S-tolyl, S/O-imidates) at
      regular concentrations and ambient temperature. 

PMID- 25765480
TI  - Correlates of HIV infection among female sex workers in Vietnam: injection drug
      use remains a key risk factor.
AB  - OBJECTIVE: Women who sell sex and use drugs have dual risks for HIV infection.
      Despite increasing reports of drug use among female sex workers (FSW) in Vietnam,
      FSW HIV interventions remain focused mainly on sexual risk reduction. We assessed
      the impact of drug use and inconsistent condom use on HIV infection among FSW in
      Vietnam, which few studies have quantified. METHODS: We surveyed 5298 women aged
      >=18 years who had sold sex in the past month from ten geographically dispersed
      provinces. We performed multivariate logistic regression on data from provinces
      with high (>=10%) or low (<10%) HIV prevalence among FSW. RESULTS: Compared to
      FSW who never used illicit drugs, the odds of HIV infection among FSW who had
      ever injected drugs and those who reported non-injection drug use were 3.44 (CI
      2.32-5.09) and 1.76 (CI 1.14-2.71), respectively, in high-prevalence provinces.
      FSW who always used condoms with clients had lower odds of HIV infection than
      those who did not (AOR=0.71; CI 0.52-0.98). In low-prevalence provinces lifetime
      injection drug use (AOR 22.05, CI 12.00-40.49), but not non-injecting drug use or
      inconsistent condom use, was significantly associated with HIV infection.
      CONCLUSIONS: Because injection drug use and inconsistent condom use were key risk
      factors for HIV infection in high-prevalence provinces, drug injection risk
      reduction should be as much a focus of HIV prevention as sexual risk reduction.
      Where HIV prevalence remains low in FSW, a more general emphasis on harm
      reduction for all drug users will benefit FSW.

PMID- 25765478
TI  - Genome-wide comparison of PU.1 and Spi-B binding sites in a mouse B lymphoma cell
      line.
AB  - BACKGROUND: Spi-B and PU.1 are highly related members of the E26-transformation
      specific (ETS) family of transcription factors that have similar, but not
      identical, roles in B cell development. PU.1 and Spi-B are both expressed in B
      cells, and have been demonstrated to redundantly activate transcription of genes
      required for B cell differentiation and function. It was hypothesized that Spi-B
      and PU.1 occupy a similar set of regions within the genome of a B lymphoma cell
      line. RESULTS: To compare binding regions of Spi-B and PU.1, murine WEHI-279
      lymphoma cells were infected with retroviral vectors encoding 3XFLAG-tagged PU.1
      or Spi-B. Anti-FLAG chromatin immunoprecipitation followed by next generation
      sequencing (ChIP-seq) was performed. Analysis for high-stringency enriched
      genomic regions demonstrated that PU.1 occupied 4528 regions and Spi-B occupied
      3360 regions. The majority of regions occupied by Spi-B were also occupied by
      PU.1. Regions bound by Spi-B and PU.1 were frequently located immediately
      upstream of genes associated with immune response and activation of B cells.
      Motif-finding revealed that both transcription factors were predominantly located
      at the ETS core domain (GGAA), however, other unique motifs were identified when
      examining regions associated with only one of the two factors. Motifs associated
      with unique PU.1 binding included POU2F2, while unique motifs in the Spi-B
      regions contained a combined ETS-IRF motif. CONCLUSIONS: Our results suggest that
      complementary biological functions of PU.1 and Spi-B may be explained by their
      interaction with a similar set of regions in the genome of B cells. However,
      sites uniquely occupied by PU.1 or Spi-B provide insight into their unique
      functions.

PMID- 25765481
TI  - Detecting initiation or risk for initiation of substance use before high school
      during pediatric well-child check-ups.
AB  - BACKGROUND: Youth substance use (SU) is prevalent and costly, affecting mental
      and physical health. American Academy of Pediatrics and Affordable Care Act call
      for SU screening and prevention. The Youth Risk Index((c)) (YRI) was tested as a
      screening tool for having initiated and propensity to initiate SU before high
      school (which forecasts SU disorder). YRI was hypothesized to have good to
      excellent psychometrics, feasibility and stakeholder acceptability for use during
      well-child check-ups. DESIGN: A high-risk longitudinal design with two cross
      sectional replication samples, ages 9-13 was used. Analyses included receiver
      operating characteristics and regression analyses. PARTICIPANTS: A one-year
      longitudinal sample (N=640) was used for YRI derivation. Replication samples were
      a cross-sectional sample (N=345) and well-child check-up patients (N=105) for
      testing feasibility, validity and acceptability as a screening tool. RESULTS: YRI
      has excellent test-retest reliability and good sensitivity and specificity for
      concurrent and one-year-later SU (odds ratios=7.44, CI=4.3-13.0) and conduct
      problems (odds ratios=7.33, CI=3.9-13.7). Results were replicated in both cross
      sectional samples. Well-child patients, parents and pediatric staff rated YRI
      screening as important, acceptable, and a needed service. CONCLUSIONS:
      Identifying at-risk youth prior to age 13 could reap years of opportunity to
      intervene before onset of SU disorder. Most results pertained to YRI's
      association with concurrent or recent past risky behaviors; further replication
      ought to specify its predictive validity, especially adolescent-onset risky
      behaviors. YRI well identifies youth at risk for SU and conduct problems prior to
      high school, is feasible and valid for screening during well-child check-ups, and
      is acceptable to stakeholders.

PMID- 25765482
TI  - The impact of marijuana decriminalization on California drivers.
AB  - BACKGROUND: The liberalization of marijuana laws has led to concerns that such
      changes will increase "drugged driving" and crash-related mortality. California
      decriminalized marijuana effective January 1, 2011; we examine the impact of this
      change on marijuana-involved driving. METHODS: We used laboratory testing from
      roadside surveys and the Fatality Analysis Reporting System (FARS) to assess
      impacts on weekend nighttime drivers and fatally injured drivers, respectively.
      We calculated marijuana prevalence (measured by laboratory-confirmed delta-9
      tetrahydrocannabinol [THC] in roadside surveys and cannabinoids in FARS) and
      compared corresponding 95% confidence intervals (CI) to identify statistically
      significant changes post-decriminalization. We also conducted multiple logistic
      regression analyses to determine whether the odds of marijuana-involved driving
      increased significantly after controlling for potential confounders. RESULTS:
      There was no statistically significant change in the prevalence of THC-positive
      driving among weekend nighttime drivers (n=894) in 2012 (9.2%; 95% CI: 6.3, 12.2)
      compared to 2010 (11.3%; 95% CI: 8.5, 14.0) or in the adjusted odds of testing
      positive for THC (adjusted odds ratio [AOR]=0.96; 95% CI: 0.57, 1.60). In
      contrast, we found a statistically significant increase in the prevalence of
      cannabinoids among fatally injured drivers in 2012 (17.8%; 95% CI: 14.6, 20.9)
      compared to the pre-decriminalization period 2008-2010 (11.8%; 95% CI: 10.3,
      13.3). The adjusted odds of testing positive for cannabinoids were also
      significantly higher in 2012 (AOR=1.67; 95% CI: 1.28, 2.18). CONCLUSIONS: Our
      study generated discrepant findings regarding the impact of decriminalization on
      marijuana-involved driving in California. Factors that may have contributed to
      these findings, particularly methodological factors, are discussed.

PMID- 25765483
TI  - Chronic intermittent ethanol exposure reduces presynaptic dopamine
      neurotransmission in the mouse nucleus accumbens.
AB  - BACKGROUND: Increasing evidence suggests that chronic ethanol exposure decreases
      dopamine (DA) neurotransmission in the nucleus accumbens (NAc), contributing to a
      hypodopaminergic state during withdrawal. However, few studies have investigated
      adaptations in presynaptic DA terminals after chronic intermittent ethanol (CIE)
      exposure. In monkeys and rats, chronic ethanol exposure paradigms have been shown
      to increase DA uptake and D2 autoreceptor sensitivity. METHODS: The current study
      examined the effects of ethanol on DA terminals in CIE exposed mice during two
      time-points after the cessation of CIE exposure. DA release and uptake were
      measured using fast scan cyclic voltammetry in NAc core slices from C57BL/6J
      mice, 0h and 72h following three weekly cycles (4 days of 16h ethanol vapor/8h
      room air/day+3 days withdrawal) of CIE vapor exposure. RESULTS: Current results
      showed that DA release was reduced, uptake rates were increased, and inhibitory
      D2-type autoreceptor activity was augmented following CIE exposure in mice.
      CONCLUSIONS: Overall, these CIE-induced adaptations in the accumbal DA system
      reduce DA signaling and therefore reveal several potential mechanisms
      contributing to a functional hypodopaminergic state during alcohol withdrawal.

PMID- 25765484
TI  - HIV-gp120 and physical dependence to buprenorphine.
AB  - BACKGROUND: Opioids are among the most effective and commonly used analgesics in
      clinical practice for severe pain. However, the use of opioid medications is
      clinically limited by several adverse properties including dependence. While
      opioid dependence is a complex health condition, the treatment of HIV-infected
      individuals with opioid dependence presents additional challenges. The goal of
      this study was to examine the physical dependence to buprenorphine in the context
      of HIV. METHODS: Young adult male rats (Sprague-Dawley) were pretreated with HIV
      1 envelope glycoprotein 120 (gp120) injected into the periaqueductal gray area
      (PAG) and we examined the impact on physical dependence to opioid. RESULTS: It
      was found that the physical dependence to methadone occurred earlier than that to
      buprenorphine, and that gp120 did not enhance or precipitate the buprenorphine
      withdrawal. CONCLUSION: The results suggest that buprenorphine could be the
      better therapeutic option to manage opioid dependence in HIV.

PMID- 25765485
TI  - Diarrhea at the Hajj and Umrah.
AB  - This systematic review aims to summarize the incidence and etiology of diarrheal
      illness among pilgrims attending the Hajj and Umrah. Gastroenteritis and diarrhea
      have been potential threats during previous Hajj pilgrimages. The last cases of
      Hajj related cholera were reported in 1989. Currently, respiratory tract
      infections account for the majority of health problems during the Hajj. This
      shift in epidemiology reflects the improvement of sanitary conditions in Saudi
      Arabia in general, and at religious sites in particular. Nevertheless,
      gastrointestinal diseases, food-poisoning outbreaks, and diarrhea continue to
      occur among pilgrims. Available studies about diarrhea among Hajj pilgrims
      indicate a mean prevalence of 2% with the highest prevalence of 23% among a group
      of French pilgrims in 2013. There is an obvious lack of information about the
      etiology of diarrheal disease at the Hajj. Further studies addressing this issue
      in hospitalized patients as well as prospective cohort studies would be of
      interest. During the Hajj, hand washing is regularly carried out by pilgrims
      under a ritual purification, often called ablution. We recommend implementation
      of effective hand hygiene practices focusing on the regular use of alcohol-based
      hand rubs, as they require less time than traditional hand washing, act more
      rapidly, and contribute to sustained improvement in compliance associated with
      decreased infection rates.

PMID- 25765486
TI  - Vector-borne diseases in Haiti: a review.
AB  - Haiti lies on the western third of the island of Hispaniola in the Caribbean, and
      is one of the poorest nations in the Western hemisphere. Haiti attracts a lot of
      medical attention and support due to severe natural disasters followed by
      disastrous health consequences. Vector-borne infections are still prevalent there
      with some unique aspects comparing it to Latin American countries and other
      Caribbean islands. Although vector-borne viral diseases such as dengue and
      recently chikungunya can be found in many of the Caribbean islands, including
      Haiti, there is an apparent distinction of the vector-borne parasitic diseases.
      Contrary to neighboring Carribbean islands, Haiti is highly endemic for malaria,
      lymphatic filariasis and mansonellosis. Affected by repeat natural disasters,
      poverty and lack of adequate infrastructure, control of transmission within Haiti
      and prevention of dissemination of vector-borne pathogens to other regions is
      challenging. In this review we summarize some aspects concerning diseases caused
      by vector-borne pathogens in Haiti. 

PMID- 25765487
TI  - Low-valent iron(i) amido olefin complexes as promotors for dehydrogenation
      reactions.
AB  - Fe(I) compounds including hydrogenases show remarkable properties and
      reactivities. Several iron(I) complexes have been established in stoichiometric
      reactions as model compounds for N2 or CO2 activation. The development of well
      defined iron(I) complexes for catalytic transformations remains a challenge. The
      few examples include cross-coupling reactions, hydrogenations of terminal
      olefins, and azide functionalizations. Here the syntheses and properties of
      bimetallic complexes [MFe(I) (trop2 dae)(solv)] (M=Na, solv=3 thf; M=Li, solv=2
      Et2 O; trop=5H-dibenzo[a,d]cyclo-hepten-5-yl, dae=(N-CH2 -CH2 -N) with a d(7) Fe
      low-spin valence-electron configuration are reported. Both compounds promote the
      dehydrogenation of N,N-dimethylaminoborane, and the former is a precatalyst for
      the dehydrogenative alcoholysis of silanes. No indications for heterogeneous
      catalyses were found. High activities and complete conversions were observed
      particularly with [NaFe(I) (trop2 dae)(thf)3 ]. 

PMID- 25765488
TI  - Combining molecular fingerprints with multidimensional scaling analyses to
      identify the source of spilled oil from highly similar suspected oils.
AB  - Oil fingerprints have been a powerful tool widely used for determining the source
      of spilled oil. In most cases, this tool works well. However, it is usually
      difficult to identify the source if the oil spill accident occurs during offshore
      petroleum exploration due to the highly similar physiochemical characteristics of
      suspected oils from the same drilling platform. In this report, a case study from
      the waters of the South China Sea is presented, and multidimensional scaling
      analysis (MDS) is introduced to demonstrate how oil fingerprints can be combined
      with mathematical methods to identify the source of spilled oil from highly
      similar suspected sources. The results suggest that the MDS calculation based on
      oil fingerprints and subsequently integrated with specific biomarkers in spilled
      oils is the most effective method with a great potential for determining the
      source in terms of highly similar suspected oils. 

PMID- 25765489
TI  - Understanding the sources of diabetes distress in adults with type 1 diabetes.
AB  - AIMS: To identify the unique sources of diabetes distress (DD) for adults with
      type 1 diabetes (T1D). METHODS: Sources of DD were developed from qualitative
      interviews with 25 T1D adults and 10 diabetes health care providers. Survey items
      were then developed and analyzed using both exploratory (EFA) and confirmatory
      CFA) analyses on two patient samples. Construct validity was assessed by
      correlations with depressive symptoms (PHQ8), complications, HbA1C, BMI, and
      hypoglycemia worry scale (HWS). Scale cut-points were created using multiple
      regression. RESULTS: An EFA with 305 U.S. participants yielded 7 coherent,
      reliable sources of distress that were replicated by a CFA with 109 Canadian
      participants: Powerlessness, Negative Social Perceptions, Physician Distress,
      Friend/Family Distress, Hypoglycemia Distress, Management Distress, Eating
      Distress. Prevalence of DD was high with 41.6% reporting at least moderate DD.
      Higher DD was reported for women, those with complications, poor glycemic
      control, younger age, without a partner, and non-White patients. CONCLUSIONS: We
      identified a profile of seven major sources of DD among T1D using a newly
      developed assessment instrument. The prevalence of DD is high and is related to
      glycemic control and several patient demographic and disease-related patient
      characteristics, arguing for a need to address DD in clinical care.

PMID- 25765491
TI  - [Bacterial infection and acute lung injury].

PMID- 25765490
TI  - Spinal RyR2 pathway regulated by the RNA-binding protein HuD induces pain
      hypersensitivity in antiretroviral neuropathy.
AB  - The antiretroviral toxic neuropathy, a distal sensory polyneuropathy associated
      with antiretroviral treatment, is a frequently occurring neurological
      complication during treatment of patients with AIDS and often leads to
      discontinuation of antiretroviral therapy. The mechanisms by which antiretroviral
      drugs contribute to the development of neuropathic pain are not known. Using
      drugs that reduce intracellular calcium ions (Ca(2+)), we investigated the
      hypothesis that altered cytosolic Ca(2+) concentration contributes to the 2',3'
      dideoxycytidine (ddC)-evoked painful neuropathy. Administration of ddC induced
      mechanical and cold allodynia, which were abolished by intrathecal administration
      of TMB-8, a blocker of Ca(2+) release from intracellular stores, and by
      ryanodine, a RyR antagonist. Treatment with the IP3R antagonist heparin prevented
      mechanical allodynia with no effect on thermal response. To further clarify the
      pathway involved, we investigated the role of HuD, a RNA binding protein involved
      in neuronal function. HuD silencing reverted both mechanical and cold allodynia
      inducing, a phenotype comparable to that of ryanodine-exposed mice. HuD binding
      to the RyR2 mRNA, the most abundant RyR isoform in the spinal cord, was
      demonstrated and RyR2 silencing prevented the ddC-induced neuropathic pain. A
      positive regulation of gene expression on CaMKIIalpha by HuD was also observed,
      but sequestration of CaMKIIalpha had no effect on ddC-induced allodynia. The
      present findings identify a spinal RyR2 pathway activated in response to ddC
      administration, involving the binding activity on RyR2 mRNA by HuD. We propose
      the modulation of the RyR2 pathway as a therapeutic perspective in the management
      of antiretroviral painful neuropathy. 

PMID- 25765492
TI  - [Pathogenicity of influenza virus and development of the ARDS].

PMID- 25765493
TI  - [GRK2 as a potential therapeutic target for septic ARDS].

PMID- 25765494
TI  - [Posttranscriptional control of inflammation by an RNase Regnase-1].

PMID- 25765495
TI  - [Sleep research with fruit fly].

PMID- 25765496
TI  - [Regulation of bone metabolism by sympathetic nervous system].

PMID- 25765497
TI  - [Open innovation of life science industry in Yokohama/Kanagawa area].

PMID- 25765498
TI  - [Pharmacological properties and clinical efficacy of daclatasvir (Daklinza(r))
      and asunaprevir (Sunvepra(r))].

PMID- 25765499
TI  - [Conversion of pancreatic delta-cells into beta-cells].

PMID- 25765500
TI  - Pharmacological profile of novel psychoactive benzofurans.
AB  - BACKGROUND AND PURPOSE: Benzofurans are newly used psychoactive substances, but
      their pharmacology is unknown. The aim of the present study was to
      pharmacologically characterize benzofurans in vitro. EXPERIMENTAL APPROACH: We
      assessed the effects of the benzofurans 5-APB, 5-APDB, 6-APB, 6-APDB, 4-APB, 7
      APB, 5-EAPB and 5-MAPDB and benzodifuran 2C-B-FLY on the human noradrenaline
      (NA), dopamine and 5-HT uptake transporters using HEK 293 cells that express the
      respective transporters. We also investigated the release of NA, dopamine and 5
      HT from monoamine-preloaded cells, monoamine receptor-binding affinity and 5-HT2A
      and 5-HT2B receptor activation. KEY RESULTS: All of the benzofurans inhibited NA
      and 5-HT uptake more than dopamine uptake, similar to
      methylenedioxymethamphetamine (MDMA) and unlike methamphetamine. All of the
      benzofurans also released monoamines and interacted with trace amine-associated
      receptor 1 (TA1 receptor), similar to classic amphetamines. Most benzofurans were
      partial 5-HT2A receptor agonists similar to MDMA, but also 5-HT2B receptor
      agonists, unlike MDMA and methamphetamine. The benzodifuran 2C-B-FLY very
      potently interacted with 5-HT2 receptors and also bound to TA1 receptors.
      CONCLUSIONS AND IMPLICATIONS: Despite very similar structures, differences were
      found in the pharmacological profiles of different benzofurans and compared with
      their amphetamine analogues. Benzofurans acted as indirect monoamine agonists
      that interact with transporters similarly to MDMA. The benzofurans also
      interacted with 5-HT receptors. This pharmacological profile probably results in
      MDMA-like entactogenic psychoactive properties. However, benzofurans induce 5
      HT2B receptor activation associated with heart valve fibrosis. The pharmacology
      of 2C-B-FLY indicates predominant hallucinogenic properties and a risk for
      vasoconstriction.

PMID- 25765502
TI  - Prevention of needle-stick injuries in healthcare facilities: a meta-analysis.
AB  - OBJECTIVE To estimate the summary effectiveness of different needle-stick injury
      (NSI)-prevention interventions. DESIGN We conducted a meta-analysis of English
      language articles evaluating methods for reducing needle stick, sharp, or
      percutaneous injuries published from 2002 to 2012 identified using PubMed and
      Medline EBSCO databases. Data were extracted using a standardized instrument.
      Random effects models were used to estimate the summary effectiveness of 3
      interventions: training alone, safety-engineered devices (SEDs) alone, and the
      combination of training and SEDs. SETTING Healthcare facilities, mainly hospitals
      PARTICIPANTS Healthcare workers including physicians, midwives, and nurses
      RESULTS From an initial pool of 250 potentially relevant studies, 17 studies met
      our inclusion criteria. Six eligible studies evaluated the effectiveness of
      training interventions, and the summary effect of the training intervention was
      0.66 (95% CI, 0.50-0.89). The summary effect across the 5 studies that assessed
      the efficacy of SEDs was 0.51 (95% CI, 0.40-0.64). A total of 8 studies evaluated
      the effectiveness of training plus SEDs, with a summary effect of 0.38 (95% CI,
      0.28-0.50). CONCLUSION Training combined with SEDs can substantially reduce the
      risk of NSIs.

PMID- 25765501
TI  - The association between antagonist hamstring coactivation and episodes of knee
      joint shifting and buckling.
AB  - OBJECTIVE: Hamstring coactivation during quadriceps activation is necessary to
      counteract the quadriceps pull on the tibia, but coactivation can be elevated
      with symptomatic knee osteoarthritis (OA). To guide rehabilitation to attenuate
      risk for mobility limitations and falls, this study evaluated whether higher
      antagonistic open kinetic chain hamstring coactivation is associated with knee
      joint buckling (sudden loss of support) and shifting (a sensation that the knee
      might give way). DESIGN: At baseline, median hamstring coactivation was assessed
      during maximal isokinetic knee extensor strength testing and at baseline and 24
      month follow-up, knee buckling and shifting was self-reported. Associations
      between tertiles of co-activation and knee (1) buckling, (2) shifting and (3)
      either buckling or shifting were assessed using logistic regression, adjusted for
      age, sex, knee OA and pain. RESULTS: 1826 participants (1089 women) were
      included. Mean +/- SD age was 61.7 +/- 7.7 years, BMI was 30.3 +/- 5.5 kg/m(2)
      and 38.2% of knees had OA. There were no consistent statistically significant
      associations between hamstring coactivation and ipsilateral prevalent or incident
      buckling or the combination of buckling and shifting. The odds ratios for
      incident shifting in the highest in comparison with the lowest tertile of
      coactivation had similar magnitudes in the combined and medial hamstrings, but
      only reached statistical significance for lateral hamstring coactivation,
      OR(95%CI) 1.53 (0.99, 2.36). CONCLUSIONS: Hamstring coactivation during an open
      kinetic chain quadriceps exercise was not consistently associated with prevalent
      or incident self-reported knee buckling or shifting in older adults with or at
      risk for knee OA.

PMID- 25765503
TI  - Portable gamma camera guidance in sentinel lymph node biopsy: prospective
      observational study of consecutive cases.
AB  - INTRODUCTION: Sentinel lymph node biopsy is the most important tool available for
      node staging in patients with melanoma. OBJECTIVES: To analyze sentinel lymph
      node detection and dissection with radio guidance from a portable gamma camera.
      To assess the number of complications attributable to this biopsy technique.
      METHODS: Prospective observational study of a consecutive series of patients
      undergoing radioguided sentinel lymph node biopsy. We analyzed agreement between
      nodes detected by presurgical lymphography, those detected by the gamma camera,
      and those finally dissected. RESULTS: A total of 29 patients (17 women [62.5%]
      and 12 men [37.5%]) were enrolled. The mean age was 52.6 years (range, 26-82
      years). The sentinel node was dissected from all patients; secondary nodes were
      dissected from some. In 16 cases (55.2%), there was agreement between the number
      of nodes detected by lymphography, those detected by the gamma camera, and those
      finally dissected. The only complications observed were seromas (3.64%). No cases
      of wound dehiscence, infection, hematoma, or hemorrhage were observed.
      CONCLUSIONS: Portable gamma-camera radio guidance may be of use in improving the
      detection and dissection of sentinel lymph nodes and may also reduce
      complications. These goals are essential in a procedure whose purpose is melanoma
      staging.

PMID- 25765504
TI  - Identifying randomized clinical trials in Spanish-language dermatology journals.
AB  - INTRODUCTION: The necessary foundation for good clinical practice lies in
      knowledge derived from clinical research. Evidence from randomized clinical
      trials (RCTs) is the pillar on which decisions about therapy are based.
      OBJECTIVE: To search exhaustively and rigorously to identify RCTs in dermatology
      journals published in Spanish. METHODS: We located dermatology journals through
      the following search engines and indexes: PubMed, LILACS, SciELO, Periodica,
      Latindex, Indice Medico Espanol, C-17, IBECS, EMBASE, and IMBIOMED. We also
      sought information through dermatology associations and dermatologists in
      countries where Spanish was the usual language of publication, and we searched
      the Internet (Google). Afterwards we searched the journals electronically and
      manually to identify RCTs in all available volumes and issues, checking from the
      year publication started through 2012. RESULTS: Of 28 journals identified, we
      included 21 in the search. We found a total of 144 RCTs published since 1969; 78
      (54%) were in Latin American journals and 66 (46%) were in Spanish journals. The
      most frequent disease contexts for RCTs in Spanish journals were psoriasis,
      mycoses, and acne vulgaris. In Latin American journals, the most frequent disease
      contexts were common warts, mycoses, acne vulgaris, and skin ulcers on the lower
      limbs. Manual searches identified more RCTs than electronic searches.
      CONCLUSIONS: Manual searches found a larger number of RCTs. Relatively fewer RCTs
      are published in Spanish and Latin American journals than in English-language
      journals. Internet facilitated access to full texts published by many journals;
      however, free open access to these texts is still unavailable and a large number
      of journal issues are still not posted online.

PMID- 25765505
TI  - One year of Oncology Research and Treatment.

PMID- 25765506
TI  - Influence of mechanical stress on palmoplantar erythrodysesthesia--a case report.
AB  - BACKGROUND: Cutaneous adverse events can have an important negative influence on
      quality of life and compliance in affected patients. Palmoplantar
      erythrodysesthesia (PPE; hand-foot syndrome) is a cutaneous toxicity associated
      with chemotherapeutic treatment, which necessitates treatment interruption or
      dose reduction in severe cases. This case report of pegylated liposomal
      doxorubicin-induced PPE shows the influence of mechanical stress on the
      development of skin lesions in various locations and the importance of patient
      education and compliance. CASE REPORT: We present the case of a 43-year-old
      female patient diagnosed with ovarian cancer and having undergone surgical and
      chemotherapeutic treatment. The development of extensive grade 3 PPE affecting
      numerous areas of the body particularly exposed to mechanical pressure
      necessitated dermatological treatment. The combination of local application of an
      antioxidant-containing ointment and the patient's compliance made it possible to
      continue chemotherapy without interruption or dose reduction. CONCLUSION: The
      development of PPE often limits the use of chemotherapeutic agents, and this case
      report can provide a possible therapeutic and preventive strategy for affected
      patients.

PMID- 25765507
TI  - Erratum.

PMID- 25765508
TI  - Assessment of an extended dataset of in vitro human dermal absorption studies on
      pesticides to determine default values, opportunities for read-across and
      influence of dilution on absorption.
AB  - Dermal absorption is a key parameter in non-dietary human safety assessments for
      agrochemicals. Conservative default values and other criteria in the EFSA
      guidance have substantially increased generation of product-specific in vitro
      data and in some cases, in vivo data. Therefore, data from 190 GLP- and OECD
      guideline-compliant human in vitro dermal absorption studies were published,
      suggesting EFSA defaults and criteria should be revised (Aggarwal et al., 2014).
      This follow-up article presents data from an additional 171 studies and also the
      combined dataset. Collectively, the data provide consistent and compelling
      evidence for revision of EFSA's guidance. This assessment covers 152
      agrochemicals, 19 formulation types and representative ranges of spray
      concentrations. The analysis used EFSA's worst-case dermal absorption definition
      (i.e., an entire skin residue, except for surface layers of stratum corneum, is
      absorbed). It confirmed previously proposed default values of 6% for liquid and
      2% for solid concentrates, irrespective of active substance loading, and 30% for
      all spray dilutions, irrespective of formulation type. For concentrates,
      absorption from solvent-based formulations provided reliable read-across for
      other formulation types, as did water-based products for solid concentrates. The
      combined dataset confirmed that absorption does not increase linearly beyond a 5
      fold increase in dilution. Finally, despite using EFSA's worst-case definition
      for absorption, a rationale for routinely excluding the entire stratum corneum
      residue, and ideally the entire epidermal residue in in vitro studies, is
      presented. 

PMID- 25765509
TI  - Principles for identification of High Potency Category Chemicals for which the
      Dermal Sensitisation Threshold (DST) approach should not be applied.
AB  - An essential step in ensuring the toxicological safety of chemicals used in
      consumer products is the evaluation of their skin sensitising potential. The
      sensitising potency, coupled with information on exposure levels, can be used in
      a Quantitative Risk Assessment (QRA) to determine an acceptable level of a given
      chemical in a given product. Where consumer skin exposure is low, a risk
      assessment can be conducted using the Dermal Sensitisation Threshold (DST)
      approach, avoiding the need to determine potency experimentally. Since skin
      sensitisation involves chemical reaction with skin proteins, the first step in
      the DST approach is to assess, on the basis of the chemical structure, whether
      the chemical is expected to be reactive or not. Our accompanying publication
      describes the probabilistic derivation of a DST of 64 MUg/cm(2) for chemicals
      assessed as reactive. This would protect against 95% of chemicals assessed as
      reactive, but the remaining 5% would include chemicals with very high potency.
      Here we discuss the chemical properties and structural features of high potency
      sensitisers, and derive an approach whereby they can be identified and
      consequently excluded from application of the DST.

PMID- 25765510
TI  - Evaluation of preparation methods for MS-based analysis of intestinal epithelial
      cell proteomes.
AB  - The gut epithelium formed between an organism and the environment plays an
      essential role in host-microbe interactions, yet remains one of the least
      characterized mammalian tissues. Especially the membrane proteins, which are
      critical to bacterial adhesion, are understudied, because these proteins are low
      in abundance, and large amounts of sample is needed for their preparation and for
      undertaking MS-based analysis. The aim of this study was to evaluate three
      different methods for isolation and preparation of pig intestinal epithelial
      cells for MS-based analysis of the proteome. Samples were analyzed by LC and
      electrospray QTOF-MS. The methods were evaluated according to efficiency, purity,
      transmembrane protein recovery, as well as for suitability to large-scale
      preparations. Our data clearly demonstrate that mucosal shaving is by far the
      best-suited method for in-depth MS analysis in terms of ease and speed of sample
      preparation, as well as protein recovery. In comparison, more gentle methods
      where intestinal epithelial cells are harvested by shaking are more time
      consuming, result in lower protein yield, and are prone to increased technical
      variation due to multiple steps involved. 

PMID- 25765511
TI  - Spontaneous Formation of Microgroove Arrays on the Surface of p-Type Porous
      Silicon Induced by a Turing Instability in Electrochemical Dissolution.
AB  - Self-organization plays an imperative role in recent materials science. Highly
      tunable, periodic structures based on dynamic self-organization at micrometer
      scales have proven difficult to design, but are desired for the further
      development of micropatterning. In the present study, we report a microgroove
      array that spontaneously forms on a p-type silicon surface during its
      electrodissolution. Our detailed experimental results suggest that the
      instability can be classified as Turing instability. The characteristic scale of
      the Turing-type pattern is small compared to self-organized patterns caused by
      the Turing instabilities reported so far. The mechanism for the miniaturization
      of self-organized patterns is strongly related to the semiconducting property of
      silicon electrodes as well as the dynamics of their surface chemistry. 

PMID- 25765513
TI  - 5-demethylnobiletin promotes the formation of polymerized tubulin, leads to G2/M
      phase arrest and induces autophagy via JNK activation in human lung cancer cells.
AB  - 5-Demethylnobiletin is a hydroxylated polymethoxyflavone found in citrus plants
      that shows antiproliferative activities in several cancer cell lines. In this
      study, we investigated the effects and underlying molecular mechanisms of 5
      demethylnobiletin on inhibition of cell growth, apoptosis, cell cycle and
      autophagy in A549 and CL1-5 lung cancer cells. The results of the 3-(4,5
      dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay suggested that 5
      demethylnobiletin inhibited cell growth in a dose- and time-dependent manner.
      Flow cytometry results suggested that 5-demethylnobiletin inhibited proliferation
      in lung cancer cells by inducing G2/M cell cycle phase arrest but predominantly
      not through apoptosis. Western blot results illustrated that the blockade of the
      cell cycle was associated with reduced levels of cdc25 and cdc2. Notably, our
      results indicated that 5-demethylnobiletin induced significant abnormal
      microtubule dynamics in A549 and CL1-5 cells, a novel finding. Studies conducted
      with isolated tubulin and docking models suggest that 5-demethylnobiletin
      promoted the polymerization of microtubules and bound to the taxol site.
      Additionally, 5-demethylnobiletin might also induce autophagy via activation of
      the JNK signaling pathway in A549 and CL1-5 cells. Pretreatment of the cells with
      the autophagy inhibitor 3-methyladenine significantly potentiated 5
      demethylnobiletin-induced apoptosis, suggesting that 5-demethylnobiletin-induced
      autophagy mitigated cell apoptosis. Further investigation revealed that 5
      demethylnobiletin inhibition of CL1-5 lung cancer cell growth was reproducible in
      a nude mouse model. Taken together, these studies suggest that 5
      demethylnobiletin has anti-lung cancer efficacy both in vitro and in vivo
      possibly through induction of G2/M arrest, autophagy and apoptosis. 

PMID- 25765512
TI  - Development of a hypoallergenic recombinant parvalbumin for first-in-man
      subcutaneous immunotherapy of fish allergy.
AB  - BACKGROUND: The FAST (food allergy-specific immunotherapy) project aims at
      developing safe and effective subcutaneous immunotherapy for fish allergy, using
      recombinant hypoallergenic carp parvalbumin, Cyp c 1. OBJECTIVES: Preclinical
      characterization and good manufacturing practice (GMP) production of mutant Cyp
      (mCyp) c 1. METHODS: Escherichia coli-produced mCyp c 1 was purified using
      standard chromatographic techniques. Physicochemical properties were investigated
      by gel electrophoresis, size exclusion chromatography, circular dichroism
      spectroscopy, reverse-phase high-performance liquid chromatography and mass
      spectrometry. Allergenicity was assessed by ImmunoCAP inhibition and basophil
      histamine release assay, immunogenicity by immunization of laboratory animals and
      stimulation of patients' peripheral blood mononuclear cells (PBMCs). Reference
      molecules were purified wild-type Cyp c 1 (natural and/or recombinant). GMP
      compliant alum-adsorbed mCyp c 1 was tested for acute toxicity in mice and
      rabbits and for repeated-dose toxicity in mice. Accelerated and real-time
      protocols were used to evaluate stability of mCyp c 1 as drug substance and drug
      product. RESULTS: Purified mCyp c 1 behaves as a folded and stable molecule.
      Using sera of 26 double-blind placebo-controlled food-challenge-proven fish
      allergic patients, reduction in allergenic activity ranged from 10- to 5,000-fold
      (1,000-fold on average), but with retained immunogenicity (immunization in
      mice/rabbits) and potency to stimulate human PBMCs. Toxicity studies revealed no
      toxic effects and real-time stability studies on the Al(OH)3-adsorbed drug
      product demonstrated at least 20 months of stability. CONCLUSION: The GMP drug
      product developed for treatment of fish allergy has the characteristics targeted
      for in FAST: i.e. hypoallergenicity with retained immunogenicity. These results
      have warranted first-in-man immunotherapy studies to evaluate the safety of this
      innovative vaccine.

PMID- 25765514
TI  - Maternal fructose-intake-induced renal programming in adult male offspring.
AB  - Nutrition in pregnancy can elicit long-term effects on the health of offspring.
      Although fructose consumption has increased globally and is linked to metabolic
      syndrome, little is known about the long-term effects of maternal high-fructose
      (HF) exposure during gestation and lactation, especially on renal programming. We
      examined potential key genes and pathways that are associated with HF-induced
      renal programming using whole-genome RNA next-generation sequencing (NGS) to
      quantify the abundance of RNA transcripts in kidneys from 1-day-, 3-week-, and 3
      month-old male offspring. Pregnant Sprague-Dawley rats received regular chow or
      chow supplemented with HF (60% diet by weight) during the entire period of
      pregnancy and lactation. Male offspring exhibited programmed hypertension at 3
      months of age. Maternal HF intake modified over 200 renal transcripts from
      nephrogenesis stage to adulthood. We observed that 20 differentially expressed
      genes identified in 1-day-old kidney are related to regulation of blood pressure.
      Among them, Hmox1, Bdkrb2, Adra2b, Ptgs2, Col1a2 and Tbxa2r are associated with
      endothelium-derived hyperpolarizing factor (EDHF). NGS also identified genes in
      arachidonic acid metabolism (Cyp2c23, Hpgds, Ptgds and Ptges) that may be
      potential key genes/pathways contributing to renal programming and hypertension.
      Collectively, our NGS data suggest that maternal HF intake elicits a defective
      adaptation of interrelated EDHFs during nephrogenesis which may lead to renal
      programming and hypertension in later life. Moreover, our results highlight genes
      and pathways involved in renal programming as potential targets for therapeutic
      approaches to prevent metabolic-syndrome-related comorbidities in children with
      HF exposure in early life. 

PMID- 25765515
TI  - Is 'bad luck' an important determinant of cancer incidence and does this concept
      apply to kidney tumors?
AB  - A study recently published in Science demonstrates a strong correlation between
      the total number of stem cell divisions and the lifetime risk of cancer in
      various organs. The tumors considered are divided into two classes, that is, D
      (Deterministic) and R (Replicative). Stochastic factors presumably attributable
      to errors deriving from DNA replication are proposed to be at the basis of R
      tumor frequency, leading to the conclusion that 'bad luck' is a primary
      determinant of certain types of cancer. The present Second Opinion highlights
      potential problems associated with the hypothesis of the study, as some of these
      also apply to kidney cancer. The aim is to point out that chance is not a major
      cause of cancer incidence because it is not substantiated by the data available
      through epidemiological evidence. In particular, we highlight that differences in
      tumor incidence associated with sex and geographic areas are not in line with the
      'bad luck' hypothesis. Further aspects of tumor biology that do not entirely fit
      with the idea that stochastic events related to DNA replication of normal stem
      cells are the heterogeneity of the cancer cell phenotype and the heterogeneity of
      intra-organ localization, often observed in tumors originating from the same
      tissue. From a public health perspective, the points discussed here as well as
      the absence of data on prevalent tumors, like breast and prostate cancer, do not
      support the oversimplified message conveyed by the media that the majority of
      cancer cases cannot be prevented. (c) 2015 S. Karger AG, Basel. 

PMID- 25765517
TI  - An examination of the variation in maternal placentae across the genus
      Poeciliopsis (Poeciliidae).
AB  - Placentae show considerable diversity in a number of nonmammalian, viviparous
      organisms, including amphibians, reptilian sauropsids, teleost fish, and
      chondrichthyes. However, the evolutionary processes driving the evolution of
      placenta are still debated. In teleost fishes, the genus Poeciliopsis
      (Poeciliidae) offers a rare opportunity for studying placental evolution:
      extensive placentation has evolved three independent times within the last
      750,000 years and there is substantial interspecific variation in the degree of
      embryonic, maternal nutrient provisioning and development of the placenta. In
      poeciliids, the placenta is composed of a hypertrophied maternal follicular
      epithelium apposed to a highly vascularized embryonic pericardial sac. To better
      understand placental evolution, we have undertaken a comprehensive comparative
      study of the maternal follicle in eight closely related Poeciliopsis species that
      span the range in postfertilization, embryonic, maternal nutrient provisioning
      (from lecithotrophs, to moderate matrotrophs, to extensive matrotrophs). Using
      light and scanning electron microscopy, we found that the species that provide
      extensive postfertilization maternal nutrient provisioning (extensive
      matrotrophs) have thicker follicles and more extensive folding of the follicular
      epithelium compared to the lecithotrophs and moderate matrotrophs. Follicle
      sections and histology revealed that epithelial folds of the extensive
      matrotrophs are comprised primarily of cuboidal and columnar cells and are richly
      supplied with capillaries. Among the extensive matrotrophs, enhancements of
      follicle traits corresponded with increases in the level of maternal nutrient
      provisioning. Hypertrophied maternal follicles with richly vascularized folds can
      serve to increase the surface area and, thus, facilitate the transfer of
      substances between the mother and developing embryo. Finally, we found egg
      envelopes in the lecithotrophs and moderate matrotrophs, but not in the extensive
      matrotrophs. Morphological studies, like this one, can provide a better
      understanding of the natural variation in the structure and functioning of
      maternal and offspring traits associated with matrotrophy and, thus, insights
      into the processes driving placental evolution. J. Morphol. 276:707-720, 2015.
      (c) 2015 Wiley Periodicals, Inc. 

PMID- 25765516
TI  - Handheld electromagnet carrier for transfer of hyperpolarized carbon-13 samples.
AB  - PURPOSE: Hyperpolarization of carbon-13 ((13) C) nuclei by dissolution dynamic
      nuclear polarization increases signal-to-noise ratio (SNR) by >10,000-fold for
      metabolic imaging, but care must be taken when transferring hyperpolarized (HP)
      samples from polarizer to MR scanner. Some (13) C substrates relax rapidly in low
      ambient magnetic fields. A handheld electromagnet carrier was designed and
      constructed to preserve polarization by maintaining a sufficient field during
      sample transfer. METHODS: The device was constructed with a solenoidal
      electromagnet, powered by a nonmagnetic battery, holding the HP sample during
      transfer. A specially designed switch automated deactivation of the field once
      transfer was complete. Phantom and rat experiments were performed to compare MR
      signal enhancement with or without the device for HP [(13) C]urea and [1-(13)
      C]pyruvate. RESULTS: The magnetic field generated by this device was tested to be
      >50 G over a 6-cm central section. In phantom and rat experiments, [(13) C]urea
      transported via the device showed SNR improvement by a factor of 1.8-1.9 over
      samples transferred through the background field. CONCLUSION: A device was
      designed and built to provide a suitably high yet safe magnetic field to preserve
      hyperpolarization during sample transfer. Comparative testing demonstrated SNR
      improvements of approximately two-fold for [(13) C]urea while maintaining SNR for
      [1-(13) C]pyruvate.

PMID- 25765518
TI  - Interaction of gas phase oxalic acid with ammonia and its atmospheric
      implications.
AB  - Oxalic acid is believed to play an important role in the formation and growth of
      atmospheric organic aerosols. However, as a common organic acid, the
      understanding of the larger clusters formed by gas phase oxalic acid with
      multiple ammonia molecules is incomplete. In this work, the structural
      characteristics and thermodynamics of oxalic acid clusters with up to six ammonia
      molecules have been investigated at the PW91PW91/6-311++G(3df,3pd) level of
      theory. We found that oxalic acid forms relatively stable clusters with ammonia
      molecules, and that ionization events play a key role. The analyses of the
      thermodynamics and atmospheric relevance indicate that the heterodimer
      (H2C2O4)(NH3) shows an obvious relative concentration in the atmosphere, and thus
      likely participates in new particle formation. However, with increasing number of
      ammonia molecules, the concentration of clusters decreases gradually.
      Additionally, clusters of oxalic acid with ammonia molecules are predicted to
      form favorably in low temperature conditions and show high Rayleigh scattering
      intensities. 

PMID- 25765519
TI  - A systematic review of dydrogesterone for the treatment of recurrent miscarriage.
AB  - The objective of this systematic review was to assesses whether the orally acting
      progestagen, dydrogesterone lowers the incidence of subsequent miscarriage in
      women with recurrent miscarriage. A computerized search was performed in Medline,
      Embase and Ovid Medline for original reports with the product name "Duphaston" or
      "dydrogesterone" and limited to clinical human data. Thirteen reports of
      dydrogesterone treatment were identified. Two randomized trials and one non
      randomized comparative trial were identified, including 509 women who fulfilled
      the criteria for meta-analysis. The number of subsequent miscarriages or
      continuing pregnancies per woman was compared in women receiving dydrogesterone
      compared to standard bed rest or placebo intervention. There was a 10.5% (29/275)
      miscarriage rate after dydrogesterone administration compared to 23.5% in control
      women (odds ratio for miscarriage 0.29 [confidence interval 0.13-0.65] and 13%
      absolute reduction in the miscarriage rate). The adverse and side effects were
      summarised in all 13 reports, and seemed to be minimal. Although all the
      predictive and confounding factors could not be controlled for, the results of
      this systematic review show a significant reduction of 29% in the odds for
      miscarriage when dydrogesterone is compared to standard care indicating a real
      treatment effect. 

PMID- 25765521
TI  - Bioremediation of pesticide-contaminated water resources: the challenge of low
      concentrations.
AB  - The use of pesticides in agricultural and urban environments has improved quality
      of life around the world. However, the resulting accumulation of pesticide
      residues in fresh water resources has negative effects on aquatic ecosystem and
      human health. Bioremediation has been proposed as an environmentally sound
      alternative for the remediation of pesticide-contaminated water resources, though
      full-scale implementation has thus far been limited. One major challenge that has
      impeded progress is the occurrence of pesticides at low concentrations. Recent
      research has improved our fundamental understanding of pesticide biodegradation
      processes occurring at low concentrations under a variety of environmental
      scenarios and is expected to contribute to the development of applied
      bioremediation strategies for pesticide-contaminated water resources. 

PMID- 25765520
TI  - Identification of a candidate stem cell in human gallbladder.
AB  - There are currently no reports of identification of stem cells in human
      gallbladder. The differences between human gallbladder and intrahepatic bile duct
      (IHBD) cells have also not been explored. The goals of this study were to
      evaluate if human fetal gallbladder contains a candidate stem cell population and
      if fetal gallbladder cells are distinct from fetal IHBD cells. We found that
      EpCAM+CD44+CD13+ cells represent the cell population most enriched for clonal
      self-renewal from primary gallbladder. Primary EpCAM+CD44+CD13+ cells gave rise
      to EpCAM+CD44+CD13+ and EpCAM+CD44+CD13- cells in vitro, and gallbladder cells
      expanded in vitro exhibited short-term engraftment in vivo. Last, we found that
      CD13, CD227, CD66, CD26 and CD49b were differentially expressed between
      gallbladder and IHBD cells cultured in vitro indicating clear phenotypic
      differences between the two cell populations. Microarray analyses of expanded
      cultures confirmed that both cell types have unique transcriptional profiles with
      predicted functional differences in lipid, carbohydrate, nucleic acid and drug
      metabolism. In conclusion, we have isolated a distinct clonogenic population of
      epithelial cells from primary human fetal gallbladder with stem cell
      characteristics and found it to be unique compared to IHBD cells. 

PMID- 25765522
TI  - Ultrasound Assessment of Umbilical Cord Morphology in the First Trimester: A
      Feasibility Study.
AB  - OBJECTIVE: The aim of this study was to determine whether morphology and
      measurement of the umbilical cord could be accurately assessed at the time of the
      11- to 13(+6)-week scan. METHODS: We conducted a prospective study of 100
      consecutive women with singleton pregnancies at 11-13(+6) weeks' gestation who
      were seen for routine aneuploidy screening. Transabdominal ultrasound scans were
      performed, and the distance between two adjacent coils of the umbilical artery
      was measured in a free loop of umbilical cord. The antenatal umbilical coiling
      index (aUCI) was calculated as the inverse of this measurement (aUCI =
      1/intercoil distance in cm). The maximum diameter of the umbilical vein was
      measured. Umbilical venous blood flow velocity was obtained using standard
      Doppler technique. Interobserver variability was assessed. A subjective
      assessment of the cord was performed using the Sepulveda system of classification
      to compare the reproducibility of the observations between two observers.
      RESULTS: The intended measurements could be obtained in all cases. The aUCI was
      found to decrease with advancing gestation, while the umbilical venous diameter
      increased with gestation. The umbilical venous blood flow velocity also increased
      with gestation. Interobserver consistency in the objective measurement of the
      aUCI was poor (kappa 0.146). However, the Sepulveda classification system was
      found to be applicable and reproducible at this period of gestation (kappa
      0.601). CONCLUSIONS: Umbilical cord morphology can be consistently studied in the
      first trimester. A subjective method of evaluation of the morphology may be a
      more reproducible technique until measurement strategies are refined and operator
      experience developed.

PMID- 25765523
TI  - Gross and Microscopic Lesions in Corals from Micronesia.
AB  - The authors documented gross and microscopic morphology of lesions in corals on 7
      islands spanning western, southern, and eastern Micronesia, sampling 76 colonies
      comprising 30 species of corals among 18 genera, with Acropora, Porites, and
      Montipora dominating. Tissue loss comprised the majority of gross lesions sampled
      (41%), followed by discoloration (30%) and growth anomaly (29%). Of 31 cases of
      tissue loss, most lesions were subacute (48%), followed by acute and chronic (26%
      each). Of 23 samples with discoloration, most were dark discoloration (40%), with
      bleaching and other discoloration each constituting 30%. Of 22 growth anomalies,
      umbonate growth anomalies composed half, with exophytic, nodular, and rugose
      growth anomalies composing the remainder. On histopathology, for 9 cases of dark
      discoloration, fungal infections predominated (77%); for 7 bleached corals,
      depletion of zooxanthellae from the gastrodermis made up a majority of
      microscopic diagnoses (57%); and for growth anomalies other than umbonate,
      hyperplasia of the basal body wall was the most common microscopic finding (63%).
      For the remainder of the gross lesions, no single microscopic finding constituted
      >50% of the total. Host response varied with the agent present on histology.
      Fragmentation of tissues was most often associated with algae (60%), whereas
      necrosis dominated (53%) for fungi. Two newly documented potentially symbiotic
      tissue-associated metazoans were seen in Porites and Montipora. Findings of
      multiple potential etiologies for a given gross lesion highlight the importance
      of incorporating histopathology in coral disease surveys. This study also expands
      the range of corals infected with cell-associated microbial aggregates. 

PMID- 25765524
TI  - The effects of congested fixtures period on tactical and physical performance in
      elite football.
AB  - The aim of this study was to examine the physical and tactical performances of a
      professional football team under congested and non-congested fixture periods. Six
      home matches of an English professional football team were analysed during
      competitive season (3 matches distancing three days from the previous fixture and
      3 matches distancing six or more days from the previous fixture). Players'
      physical performances were measured by the total distance covered and distance
      covered at different speed categories. Tactical performances were measured by the
      percentage of time of players' movement synchronisation of lateral and
      longitudinal displacements. This variable was calculated considering all the
      possible pairs of outfield players, for the overall match and at different speed
      categories. Results showed no differences in the physical performance, although
      players' spent more time synchronised during the non-congested fixtures compared
      to congested fixtures, both for lateral (41.26% to 38.51%, ES: -0.3, P < 0.001)
      and longitudinal displacements (77.22% to 74.48%, ES: -0.5, P < 0.001). These
      coordination differences were particularly evident at the lower speed categories
      and in dyads composed by positions that tend to be further apart during the
      match, typically central and wing positioned players. Tactical performance seems
      to be affected by fixtures distribution, with players' spending more time
      synchronised during the non-congested fixtures. As players' cover the same amount
      of distance at similar intensities in both fixtures distribution, this reduction
      of synchronisation may be associated with an increased perception of fatigue and
      consequent adaptation strategies. 

PMID- 25765525
TI  - A very rare clinical case of a holstein heifer with two vulvae and a scrotum.
AB  - The physical and gynecological examination of a Holstein heifer single-born with
      a disorder of sexual development showed anatomical abnormalities such as the
      presence of a scrotum and 2 vulvae and an anal sphincter that was positioned on
      the right side of the body. Also, an early pregnancy was diagnosed. Cytogenetic
      and hormone analysis was requested, and the animal showed normal female
      metaphases (60,XX) and hormonal profiles. However, in gross anatomy and
      histological examinations, a structure compatible with a penis, the absence of a
      uterine body, 2 exophytic structures, and a septum in the vagina were detected.

PMID- 25765526
TI  - Normal liver sparing by proton beam therapy for hepatocellular carcinoma:
      Comparison with helical intensity modulated radiotherapy and volumetric modulated
      arc therapy.

PMID- 25765532
TI  - Does the obesity survival paradox of dialysis patients differ with age?
AB  - BACKGROUND: The obesity paradox of hemodialysis patients (the association between
      obesity and survival) could be modified by age. We hypothesize that whereas
      obesity associates with survival in elderly patients, it behaves as a mortality
      risk marker in younger individuals. METHODS: Retrospective study of 2002-2010
      adult incident hemodialysis to analyze the relationship between body mass index
      (BMI) and annual body weight changes with mortality in different age strata.
      RESULTS: Included in the study were 6,290 individuals. A progressive decrease in
      mortality was associated with increasing BMI ranges. Both annual body weight
      gains and losses were associated with mortality. Similar results were observed in
      elderly individuals, but in the BMI values of young patients, there were no
      significant differences in mortality. CONCLUSION: There is a survival benefit
      with increasing BMI in patients overall. However, while these results persist in
      patients >65 years, in young people there are no changes in mortality. Patients
      with the highest inter-annual variability in weight have an increased risk.

PMID- 25765533
TI  - Yeast strains as potential aroma enhancers in dry fermented sausages.
AB  - Actual healthy trends produce changes in the sensory characteristics of dry
      fermented sausages therefore, new strategies are needed to enhance their aroma.
      In particular, a reduction in the aroma characteristics was observed in reduced
      fat and salt dry sausages. In terms of aroma enhancing, generally coagulase
      negative cocci were selected as the most important group from the endogenous
      microbiota in the production of flavour compounds. Among the volatile compounds
      analysed in dry sausages, ester compounds contribute to fruity aroma notes
      associated with high acceptance of traditional dry sausages. However, the origin
      of ester compounds in traditional dry sausages can be due to other microorganisms
      as lactic acid bacteria, yeast and moulds. Yeast contribution in dry fermented
      sausages was investigated with opposite results attributed to low yeast survival
      or low activity during processing. Generally, they affect sausage colour and
      flavour by their oxygen-scavenging and lipolytic activities in addition to, their
      ability to catabolize fermentation products such as lactate increasing the pH and
      contributing to less tangy and more aromatic sausages. Recently, the isolation
      and characterization of yeast from traditional dry fermented sausages made
      possible the selection of those with ability to produce aroma active compounds.
      Molecular methods were used for genetic typing of the isolated yeasts whereas
      their ability to produce aroma compounds was tested in different systems such as
      in culture media, in model systems and finally on dry fermented sausages. The
      results revealed that the appropriate selection of yeast strains with aroma
      potential may be used to improve the sensory characteristics of reformulated
      fermented sausages. 

PMID- 25765534
TI  - Analyzing small data sets using Bayesian estimation: the case of posttraumatic
      stress symptoms following mechanical ventilation in burn survivors.
AB  - Background : The analysis of small data sets in longitudinal studies can lead to
      power issues and often suffers from biased parameter values. These issues can be
      solved by using Bayesian estimation in conjunction with informative prior
      distributions. By means of a simulation study and an empirical example concerning
      posttraumatic stress symptoms (PTSS) following mechanical ventilation in burn
      survivors, we demonstrate the advantages and potential pitfalls of using Bayesian
      estimation. Methods : First, we show how to specify prior distributions and by
      means of a sensitivity analysis we demonstrate how to check the exact influence
      of the prior (mis-) specification. Thereafter, we show by means of a simulation
      the situations in which the Bayesian approach outperforms the default, maximum
      likelihood and approach. Finally, we re-analyze empirical data on burn survivors
      which provided preliminary evidence of an aversive influence of a period of
      mechanical ventilation on the course of PTSS following burns. Results : Not
      suprisingly, maximum likelihood estimation showed insufficient coverage as well
      as power with very small samples. Only when Bayesian analysis, in conjunction
      with informative priors, was used power increased to acceptable levels. As
      expected, we showed that the smaller the sample size the more the results rely on
      the prior specification. Conclusion : We show that two issues often encountered
      during analysis of small samples, power and biased parameters, can be solved by
      including prior information into Bayesian analysis. We argue that the use of
      informative priors should always be reported together with a sensitivity
      analysis. 

PMID- 25765535
TI  - Corrigendum: the work mechanism and sub-bandgap-voltage electroluminescence in
      inverted quantum dot light-emitting diodes.

PMID- 25765536
TI  - L-Tryptophan as a Novel Potential Pharmacological Treatment for Wound Healing via
      Aryl Hydrocarbon Receptor Activation.
AB  - BACKGROUND: The aryl hydrocarbon receptor has been shown to be involved in wound
      healing. OBJECTIVE: The aim of this study was to assess the effect of tryptophan
      on wound healing in vitro and in a clinical trial. METHODS: The ability of
      tryptophan and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) to increase wound
      healing was assessed in an in vitro scratch wound model in human keratinocytes.
      Topical tryptophan and vehicle were assessed for 12 weeks in 51 patients with
      lower limb ulcers that were resistant to conventional therapies. RESULTS: TCDD
      0.1 nM and tryptophan 1 uM increased the rate of scratch recovery in a culture
      model. Topical tryptophan induced stronger pain relief and faster re
      epithelialization than its vehicle in patients with lower limb ulcers.
      CONCLUSION: Tryptophan shows promising potential as a novel topical treatment for
      wound healing.

PMID- 25765537
TI  - The neonatal brain is not protected by osteopontin peptide treatment after
      hypoxia-ischemia.
AB  - Neonatal encephalopathy due to perinatal hypoxia-ischemia (HI) is a severe
      condition, and current treatment options are limited. Expression of endogenous
      osteopontin (OPN), a multifunction glycoprotein, is strongly upregulated in the
      brain after neonatal HI. Intracerebrally administered OPN has been shown to be
      neuroprotective following experimental neonatal HI and adult stroke. In the
      present study, we determined whether intranasal, intraperitoneal or intracerebral
      treatment with a smaller TAT-OPN peptide is neuroprotective in neonatal mice with
      HI brain damage. The TAT-OPN peptide exerts bioactivity as it was as potent as
      full-length OPN in inducing cell adhesion in an in vitro adhesion assay.
      Intranasal administration of TAT-OPN peptide immediately after HI (T0) or in a
      repetitive treatment schedule of T0, 3 h, day (D) 1, 2 and 3 after HI did not
      protect cerebral gray or white matter after HI. Intraperitoneal TAT-OPN treatment
      at T0 or in two extended treatment schedules (D5, 7, 9, 11, 13, 15 after HI or
      T0, D1, 3, 5, 7, 9, 11, 13 and 15 after HI) did not result in neuroprotection
      either. Moreover, no functional improvement (cylinder rearing test and adhesive
      removal task) was observed following TAT-OPN treatment in any of the
      intraperitoneal treatment schedules. We validated that the TAT-OPN peptide
      reached the brain after intranasal or intraperitoneal administration by using an
      HIV-TAT staining. Finally, also intracerebral administration of the TAT-OPN
      peptide 1 h after HI did not reduce cerebral damage. Our data show that
      administration of the TAT-OPN peptide did not exert neuroprotective effects on
      neonatal HI-induced brain injury or sensorimotor behavioral deficits.

PMID- 25765538
TI  - Improved survival of incident patients with high-volume haemodiafiltration: a
      propensity-matched cohort study with inverse probability of censoring weighting.
AB  - BACKGROUND: Haemodiafiltration (HDF) is the preferred dialysis modality in many
      countries. The aim of the study was to compare the survival of incident patients
      on high-volume HDF (HV-HDF) with high-flux haemodialysis (HD) in a large-scale
      European dialysis population. METHODS: The study population was extracted from
      47,979 patients in 369 NephroCare centres throughout 12 countries. Baseline was
      six months after dialysis initiation; maximum follow-up was 5 years. Patients
      were either on HV-HDF (defined as with >=21 litres substitution fluid volume per
      session) or on HD if on that treatment for >=75% of the 3 months before baseline.
      The main predictor was treatment modality. Other parameters included country,
      age, gender, BMI, haemoglobin, albumin and Charlson comorbidity index. Propensity
      score matching and Inverse Probability of Censoring Weighting (IPCW) were applied
      to reduce bias by indication and consider modality crossover, respectively.
      RESULTS: After propensity score matching, 1,590 incident patients remained.
      Kaplan-Meier and proportional Cox regression analyses revealed no significant
      survival advantage of HV-HDF. Results were biased by modality crossover: during
      the 5-year study period, 7% of HV-HDF patients switched to HD, and 55% of HD
      patients switched to HV-HDF. IPCW uncovered a statistically significant survival
      advantage of HV-HDF (OR 0.501; CI 0.366-0.684; p < 0.001). A higher benefit of HV
      HDF for some subgroups was revealed, for example, non-diabetics, patients 65-74
      years, patients with obesity or high blood pressure. CONCLUSIONS: This large
      scale study supports the generalizability of previous RCT findings regarding the
      survival benefit of HV-HDF. Sub-group analysis showed that some sub-cohorts
      appear to benefit more from HV-HDF than others.

PMID- 25765539
TI  - Tissue- and time-dependent transcription in Ixodes ricinus salivary glands and
      midguts when blood feeding on the vertebrate host.
AB  - Ixodes ricinus is a tick that transmits the pathogens of Lyme and several
      arboviral diseases. Pathogens invade the tick midgut, disseminate through the
      hemolymph, and are transmitted to the vertebrate host via the salivary glands;
      subverting these processes could be used to interrupt pathogen transfer. Here, we
      use massive de novo sequencing to characterize the transcriptional dynamics of
      the salivary and midgut tissues of nymphal and adult I. ricinus at various time
      points after attachment on the vertebrate host. Members of a number of gene
      families show stage- and time-specific expression. We hypothesize that gene
      expression switching may be under epigenetic control and, in support of this,
      identify 34 candidate proteins that modify histones. I. ricinus-secreted proteins
      are encoded by genes that have a non-synonymous to synonymous mutation rate even
      greater than immune-related genes. Midgut transcriptome (mialome) analysis
      reveals several enzymes associated with protein, carbohydrate, and lipid
      digestion, transporters and channels that might be associated with nutrient
      uptake, and immune-related transcripts including antimicrobial peptides. This
      publicly available dataset supports the identification of protein and gene
      targets for biochemical and physiological studies that exploit the transmission
      lifecycle of this disease vector for preventative and therapeutic purposes. 

PMID- 25765540
TI  - A comparative finite elemental analysis of glass abutment supported and
      unsupported cantilever fixed partial denture.
AB  - OBJECTIVE: The purpose of this study was to investigate and compare the load
      distribution and displacement of cantilever prostheses with and without glass
      abutment by three dimensional finite element analysis. Micro-computed tomography
      was used to study the relationship between the glass abutment and the ridge.
      METHODS: The external surface of the maxilla was scanned, and a simplified finite
      element model was constructed. The ZX-27 glass abutment and the maxillary first
      and second premolars were created and modified. The solid model of the three-unit
      cantilever fixed partial denture was scanned, and the fitting surface was
      modified with reference to the created abutments using the 3D CAD system. The
      finite element analysis was completed in ANSYS. The fit and total gap volume
      between the glass abutment and dental model were determined by Skyscan 1173 high
      energy spiral micro-CT scan. RESULTS: The results of the finite element analysis
      in this study showed that the cantilever prosthesis supported by the glass
      abutment demonstrated significantly less stress on the terminal abutment and
      overall deformation of the prosthesis under vertical and oblique load. Micro
      computed tomography determined a gap volume of 6.74162 mm(3). SIGNIFICANCE: By
      contacting the mucosa, glass abutments transfer some amount of masticatory load
      to the residual alveolar ridge, thereby preventing damage to the periodontal
      microstructures of the terminal abutment. The passive contact of the glass
      abutment with the mucosa not only preserves the health of the mucosa covering the
      ridge but also permits easy cleaning. It is possible to increase the success rate
      of cantilever FPDs by supporting the cantilevered pontic with glass abutments.

PMID- 25765541
TI  - Suppressed rate of carcinogenesis and decreases in tumour volume and lung
      metastasis in CXCL14/BRAK transgenic mice.
AB  - Cancer progression involves carcinogenesis, an increase in tumour size, and
      metastasis. Here, we investigated the effect of overexpressed CXC chemokine
      ligand 14 (CXCL14) on these processes by using CXCL14/BRAK (CXCL14) transgenic
      (Tg) mice. The rate of AOM/DSS-induced colorectal carcinogenesis in these mice
      was significantly lower compared with that for isogenic wild type C57BL/6 (Wt)
      mice. When tumour cells were injected into these mice, the size of the tumours
      that developed and the number of metastatic nodules in the lungs of the animals
      were always significantly lower in the Tg mice than in the Wt ones. Injection of
      anti-asialo-GM1 antibodies to the mice before and after injection of tumour cells
      attenuated the suppressing effects of CXCL14 on the tumor growth and metastasis,
      suggesting that NK cell activity played an important role during CXCL14-mediated
      suppression of tumour growth and metastasis. The importance of NK cells on the
      metastasis was also supported when CXCL14 was expressed in B16 melanoma cells.
      Further, the survival rates after tumour cell injection were significantly
      increased for the Tg mice. As these Tg mice showed no obvious abnormality, we
      propose that CXCL14 to be a promising molecular target for cancer
      suppression/prevention. 

PMID- 25765542
TI  - Novel macrolide-resistance genes, mef(C) and mph(G), carried by plasmids from
      Vibrio and Photobacterium isolated from sediment and seawater of a coastal
      aquaculture site.
AB  - The aim of this study was to determine whether mef(C) and mph(G), originally
      found on the transferable multi-drug plasmid pAQU1 from Photobacterium damselae
      subsp. damselae isolated from seawater of a fish farm, are responsible for
      conferring macrolide resistance. Since these genes are localized head-to-tail on
      pAQU1 and only four nucleotides exist between them, the single- and combination
      effect of these genes was examined. When mph(G) alone was introduced to
      Escherichia coli, the minimum inhibitory concentrations (MICs) against
      erythromycin, clarithromycin and azithromycin increased, whereas introduction of
      mef(C) alone did not influence macrolide susceptibility. Introduction of both
      mef(C) and mph(G) dramatically increased the MICs to the same three macrolides,
      i.e. >512 MUg ml(-1) , >512 MUg ml(-1) and 128 MUg ml(-1) respectively. These
      results suggest that the macrolide phosphotransferase encoded by mph(G) is
      essential for macrolide resistance, while the efflux pump encoded by mef(C) is
      required for high-level macrolide resistance. The tandem-pair arrangements of the
      mef(C) and mph(G) genes were conserved on plasmids ranging in size from 240 to
      350 kb of the 22 erythromycin-resistant strains belonging to Vibrio and
      Photobacterium obtained from the fish farm. Sixteen of 22 plasmids ranged in size
      from 300 to 350 kb. This is the first report of novel macrolide resistance genes
      originating from a marine bacterium. SIGNIFICANCE AND IMPACT OF THE STUDY: In
      this study, mef(C) and mph(G) were found to be novel macrolide-resistance genes,
      and this is the first report of macrolide-resistance genes originating from a
      marine bacterium. These genes may be responsible for previously reported cases of
      the emergence of erythromycin-resistant bacteria in aquaculture sites by an
      unknown mechanism. The introduction of the tandem arrangement of the mef(C) and
      mph(G) genes in Escherichia coli increased the MICs to erythromycin,
      clarithromycin and azithromycin, suggesting a novel mechanism conferring high
      level macrolide resistance via combined expression of the efflux pump and
      macrolide phosphotransferase.

PMID- 25765543
TI  - Second generation tyrosine kinase inhibitors prevent disease progression in high
      risk (high CIP2A) chronic myeloid leukaemia patients.
AB  - High cancerous inhibitor of PP2A (CIP2A) protein levels at diagnosis of chronic
      myeloid leukaemia (CML) are predictive of disease progression in imatinib-treated
      patients. It is not known whether this is true in patients treated with second
      generation tyrosine kinase inhibitors (2G TKI) from diagnosis, and whether 2G
      TKIs modulate the CIP2A pathway. Here, we show that patients with high diagnostic
      CIP2A levels who receive a 2G TKI do not progress, unlike those treated with
      imatinib (P=<0.0001). 2G TKIs induce more potent suppression of CIP2A and c-Myc
      than imatinib. The transcription factor E2F1 is elevated in high CIP2A patients
      and following 1 month of in vivo treatment 2G TKIs suppress E2F1 and reduce
      CIP2A; these effects are not seen with imatinib. Silencing of CIP2A, c-Myc or
      E2F1 in K562 cells or CML CD34+ cells reactivates PP2A leading to BCR-ABL
      suppression. CIP2A increases proliferation and this is only reduced by 2G TKIs.
      Patients with high CIP2A levels should be offered 2G TKI treatment in preference
      to imatinib. 2G TKIs disrupt the CIP2A/c-Myc/E2F1 positive feedback loop, leading
      to lower disease progression risk. The data supports the view that CIP2A inhibits
      PP2Ac, stabilising E2F1, creating a CIP2A/c-Myc/E2F1 positive feedback loop,
      which imatinib cannot overcome.

PMID- 25765544
TI  - The DEK oncoprotein and its emerging roles in gene regulation.
AB  - The DEK oncogene is highly expressed in cells from most human tissues and
      overexpressed in a large and growing number of cancers. It also fuses with the
      NUP214 gene to form the DEK-NUP214 fusion gene in a subset of acute myeloid
      leukemia. Originally characterized as a member of this translocation, DEK has
      since been implicated in epigenetic and transcriptional regulation, but its role
      in these processes is still elusive and intriguingly complex. Similarly
      multifaceted is its contribution to cellular transformation, affecting multiple
      cellular processes such as self-renewal, proliferation, differentiation,
      senescence and apoptosis. Recently, the roles of the DEK and DEK-NUP214 proteins
      have been elucidated by global analysis of DNA binding and gene expression, as
      well as multiple functional studies. This review outlines recent advances in the
      understanding of the basic functions of the DEK protein and its role in
      leukemogenesis. 

PMID- 25765545
TI  - Safety and efficacy of Temsirolimus in combination with Bendamustine and
      Rituximab in relapsed mantle cell and follicular lymphoma.
AB  - In this phase I/II study, we explored the combination of Temsirolimus with
      Bendamustine and Rituximab (BeRT) in patients with r/r follicular lymphoma (FL)
      or mantle cell lymphoma (MCL). Patients with 1-3 prior therapies received
      Bendamustine (90 mg/m(2), day 1+2) and Rituximab (375 mg/m(2), day 1) with
      Temsirolimus in doses from 25 to 75 mg added on day 1, 8, 15 of a 28-day cycle.
      Fifteen (11 MCL, 4 FL) patients were included in the phase I. Median age was 73
      years and median pretreatment number was 2. No formal dose-limiting toxicity was
      observed. Dominant non-hematological side effects were fatigue in 11 (73%),
      nausea in 9 (60%), mucositis in 7 (47%) and vomiting in 6 patients (40%). Cough,
      diarrhea, pyrexia and rash were observed in five patients (33%) each. Grade 3/4
      events included leukopenia in 6 (40%), neutropenia in 4 (27%) and
      thrombocytopenia in 2 patients (13%). An objective response was observed in 14/15
      patients (93%), including 5 complete response (33%; all MCL). After a median
      follow-up of 19 months, 67% of patients are without signs of progression.
      Temsirolimus can be safely added to BR with promising preliminary activity.
      Recruitment in phase II is ongoing.

PMID- 25765546
TI  - Effects of aging and acid reflux on esophageal motility.
AB  - BACKGROUNDS: It is generally thought that esophageal motility decreases with age;
      however, a decrease in esophageal motility may also be caused by esophagitis. The
      aim of this study is to investigate the effects of aging and acid reflux on
      esophageal motility. METHODS: 40 young (under 45) healthy subjects (HS), 40
      elderly (over 65) HS, and 40 elderly (over 65) patients with mild reflux
      esophagitis (RE), underwent esophageal high-resolution manometry (HRM). Lower
      esophageal sphincter pressure (LESP), primary peristalsis (PP), and secondary
      peristalsis (SP) were evaluated. RESULTS: There was no difference in the LESP and
      also in the success rate of PP between young and elderly HS or between elderly HS
      and RE. There was no difference in the distal contractile integral (DCI) of PP
      and SP between the young and elderly HS, but in the elderly RE, it was
      significantly lower than in the elderly HS. There was no difference in the
      success rate of SP between elderly HS and RE, but in elderly HS it was
      significantly lower than in young HS. CONCLUSIONS: Aging may cause a decrease in
      the success rate of SP, and acid reflux itself may cause a decrease of the DCI in
      PP and SP.

PMID- 25765549
TI  - Time course of adipose tissue dysfunction associated with antioxidant defense,
      inflammatory cytokines and oxidative stress in dyslipemic insulin resistant rats.
AB  - The dysfunctional adipose tissue of rats fed a sucrose-rich diet was investigated
      following the time course of the development of oxidative stress, changes in
      proinflammatory cytokines and adiponectin levels, and their relationship with
      insulin resistance. We analyzed the morphometric characteristics of epididymal
      adipocytes, de novo lipogenesis enzyme activities and cellular antioxidant
      defense, inflammatory mediators, adiponectin levels and insulin resistance in
      rats fed a sucrose-rich diet for 3, 15 or 30 weeks and compared to those fed a
      control diet. The results showed a depletion of antioxidant enzyme activities in
      the fat pads of rats fed a sucrose-rich diet, with an increase in xanthine
      oxidase activity and lipid peroxidation after 3, 15 and 30 weeks on the diet.
      Superoxide dismutase activity and the redox state of glutathione showed a
      significant decrease at weeks 15 and 30. This was accompanied by visceral
      adiposity and enhanced lipogenic enzyme activities. An increase in the plasma
      levels of proinflammatory markers (TNF-alpha and IL-6) was recorded only after 30
      weeks on the diet. A reduction in plasma adiponectin levels accompanied the time
      course of deterioration of whole-body insulin sensitivity. The results suggest
      that lipid peroxidation, depletion of antioxidant defenses and changes in
      inflammatory cytokines induced by a sucrose-rich diet contribute to the
      dysregulation of adipose tissue and insulin resistance. Finally, these results
      show that the progressive deterioration of adipose tissue function, which begins
      in the absence of both visceral adiposity and overweight, is highly dependent on
      the length of time on the diet. 

PMID- 25765548
TI  - A genome-wide scan for signatures of directional selection in domesticated pigs.
AB  - BACKGROUND: Animal domestication involved drastic phenotypic changes driven by
      strong artificial selection and also resulted in new populations of breeds,
      established by humans. This study aims to identify genes that show evidence of
      recent artificial selection during pig domestication. RESULTS: Whole-genome
      resequencing of 30 individual pigs from domesticated breeds, Landrace and
      Yorkshire, and 10 Asian wild boars at ~16-fold coverage was performed resulting
      in over 4.3 million SNPs for 19,990 genes. We constructed a comprehensive genome
      map of directional selection by detecting selective sweeps using an F ST-based
      approach that detects directional selection in lineages leading to the
      domesticated breeds and using a haplotype-based test that detects ongoing
      selective sweeps within the breeds. We show that candidate genes under selection
      are significantly enriched for loci implicated in quantitative traits important
      to pig reproduction and production. The candidate gene with the strongest signals
      of directional selection belongs to group III of the metabolomics glutamate
      receptors, known to affect brain functions associated with eating behavior,
      suggesting that loci under strong selection include loci involved in behaviorial
      traits in domesticated pigs including tameness. CONCLUSIONS: We show that a
      significant proportion of selection signatures coincide with loci that were
      previously inferred to affect phenotypic variation in pigs. We further identify
      functional enrichment related to behavior, such as signal transduction and
      neuronal activities, for those targets of selection during domestication in pigs.

PMID- 25765547
TI  - A systems genetics study of swine illustrates mechanisms underlying human
      phenotypic traits.
AB  - BACKGROUND: The pig, which shares greater similarities with human than with
      mouse, is important for agriculture and for studying human diseases. However,
      similarities in the genetic architecture and molecular regulations underlying
      phenotypic variations in humans and swine have not been systematically assessed.
      RESULTS: We systematically surveyed ~500 F2 pigs genetically and phenotypically.
      By comparing candidates for anemia traits identified in swine genome-wide SNP
      association and human genome-wide association studies (GWAS), we showed that both
      sets of candidates are related to the biological process "cellular lipid
      metabolism" in liver. Human height is a complex heritable trait; by integrating
      genome-wide SNP data and human adipose Bayesian causal network, which closely
      represents bone transcriptional regulations, we identified PLAG1 as a causal gene
      for limb bone length. This finding is consistent with GWAS findings for human
      height and supports the common genetic architecture between swine and humans. By
      leveraging a human protein-protein interaction network, we identified two
      putative candidate causal genes TGFB3 and DAB2IP and the known regulators MESP1
      and MESP2 as responsible for the variation in rib number and identified the
      potential underlying molecular mechanisms. In mice, knockout of Tgfb3 and Tgfb2
      together decreases rib number. CONCLUSION: Our findings show that integrative
      network analyses reveal causal regulators underlying the genetic association of
      complex traits in swine and that these causal regulators have similar effects in
      humans. Thus, swine are a potentially good animal model for studying some complex
      human traits that are not under intense selection.

PMID- 25765551
TI  - Critical adsorption of a flexible polymer on a stripe-patterned surface.
AB  - The adsorption and dynamics of a polymer chain on a stripe-patterned surface
      composed of periodical attractive and neutral stripes are studied by using Monte
      Carlo simulation. The critical adsorption temperature Tc and pattern-recognition
      temperature Tr are estimated from the desorption probability, surface contact
      number, and bridge number. A phase diagram presenting three polymer states,
      including a desorbed state above Tc, a multi-stripe adsorbed state at an
      intermediate temperature Tr < T < Tc, and a single-stripe adsorbed state below
      Tr, is provided for infinitely long chains. Normal diffusion is always observed
      for a polymer in the direction parallel to the stripe even at low temperature.
      But in the direction perpendicular to the stripe, the polymer can freely diffuse
      above Tc, whereas the polymer is confined to one attractive stripe below Tr.
      However, the adsorbed polymer can hop from one attractive stripe to another at
      the intermediate temperature Tr < T < Tc. 

PMID- 25765550
TI  - Conservation genetics of two island endemic Ribes spp. (Grossulariaceae) of
      Sardinia: survival or extinction?
AB  - Measuring levels of population genetic diversity is an important step for
      assessing the conservation status of rare or endangered plant species and
      implementing appropriate conservation strategies. Populations of Ribes
      multiflorum subsp. sandalioticum and R. sardoum, two endangered endemic species
      from Sardinia, representing the whole genus on the island, were investigated
      using ISSR and SSR markers to determine levels and structure of genetic
      variability in their natural populations. Results indicated medium to low genetic
      diversity at the population level: Nei's gene diversity for ISSR markers ranged
      from 0.0840 to 0.1316; the expected heterozygosity (HE ) for SSR ranged from
      0.4281 to 0.7012. In addition, only one remnant population of R. sardoum showed a
      high level of inbreeding, in accordance with its very small size. Regarding the
      structure of the six R. sandalioticum populations, both principal coordinates
      analysis (PCoA) and STRUCTURE analysis of ISSR and SSR data highlighted low
      population structure, although two populations appeared to be clearly distinct
      from the others. The genetic pattern of the two taxa associated with their
      different ecological positions indicated resilience of R. sandalioticum
      populations in fresh and humid habitats and uncertain future resistance for the
      residual R. sardoum population in xeric calcareous stands. Hence, this study
      highlights the importance of an integrated conservation approach (genetic plus in
      situ and ex situ conservation studies/measures) for activating management
      programmes in these endemic and threatened taxa that can be considered as crop
      wild relatives of cultivated Ribes species.

PMID- 25765552
TI  - Serum galectin-3 as a potential marker for gastric cancer.
AB  - BACKGROUND: The identification of cancer biomarkers can advance the possibility
      for early detection and better monitoring of tumor progression. The aim of this
      study was to assess the diagnostic and prognostic value of serum galectin-3(Gal
      3) in patients with gastric cancer (GC). MATERIAL AND METHODS: We measured serum
      Gal-3 levels using ELISA method in 87 patients with GC, 53 patients with benign
      gastric lesions, and 51 healthy controls. RESULTS: Serum levels of Gal-3 in
      patients with GC were significantly higher than those in benign disease patients
      and healthy controls (P<0.001), but no difference was found between benign
      disease patients and healthy controls (P=0.635). Additionally, serum Gal-3 level
      was associated with lymph node metastasis (P=0.001) and distant metastasis
      (P<0.001), whereas it was not related to gender (P=0.204), age (P=0.269), tumor
      size (P=0.399), location (P=0.715), TNM stage (P=0.385), differentiation
      (P=0.135), or invasion depth (P=0.273). The Kaplan-Meier survival analysis
      revealed that overall survival rates in patients with high Gal-3 levels were not
      significantly different that those with low Gal-3 levels (P=0.099). CONCLUSIONS:
      Results of the current study suggests that serum Gal-3 represents a potential
      diagnostic marker for patients with GC, and may be an adjunct to determine the
      individual prognosis of these patients.

PMID- 25765553
TI  - Closing the mortality gap after a myocardial infarction in people with and
      without chronic obstructive pulmonary disease.
AB  - OBJECTIVE: Patients with chronic obstructive pulmonary disease (COPD) have
      increased mortality following myocardial infarction (MI) compared with patients
      without COPD. We investigated the extent to which differences in recognition and
      management after MI could explain the mortality difference. METHODS: 300 161
      patients with a first MI between 2003 and 2013 were identified in the UK
      Myocardial Ischaemia National Audit Project database. Logistic regression was
      used to compare mortality in hospital and at 180 days postdischarge between
      patients with and without COPD. Variables relating to inhospital factors (delay
      in diagnosis, use of reperfusion and time to reperfusion/use of angiography) and
      use of secondary prevention were sequentially added to models. RESULTS: Mortality
      was higher for patients with COPD both inhospital (4.6% vs 3.2%) and at 180 days
      (12.8% vs 7.7%). After adjusting for inhospital factors, the effect of COPD on
      inhospital mortality after MI was reduced for both ST-elevation myocardial
      infarctions (STEMIs) and non-STEMIs (STEMIs OR 1.24 (95% CI 1.10 to 1.41) to 1.13
      (95% CI 0.99 to 1.29); non-STEMIs OR 1.34 (95% CI 1.24 to 1.45) to 1.16 (95% CI
      1.07 to 1.26)). Adjusting for inhospital factors reduced the effect of COPD on
      mortality after non-STEMI at 180 days (OR 1.56 (95% CI 1.47 to 1.65) to 1.37 (95%
      CI 1.31 to 1.44)). Adjusting for use of secondary prevention also reduced the
      effect of COPD on mortality at 180 days for STEMIs and non-STEMIs (STEMIs OR 1.45
      (95% CI 1.31 to 1.61) to 1.25 (95% CI 1.11 to 1.41); non-STEMIs OR 1.37 (95% CI
      1.31 to 1.44) to 1.26 (95% CI 1.17 to 1.35). CONCLUSIONS: Delayed diagnosis,
      timing and use of reperfusion of a STEMI, use of angiography after a non-STEMI
      and use of secondary prevention medicines are all potential explanations for the
      mortality gap after MI in people with COPD.

PMID- 25765555
TI  - Outcomes after Second Hematopoietic Stem Cell Transplantations in Pediatric
      Patients with Relapsed Hematological Malignancies.
AB  - Relapse of hematological malignancies after hematopoietic stem cell
      transplantation (HCT) is associated with poor prognosis. A second HCT represents
      one of the few therapeutic options for these high-risk patients. For children
      undergoing second HCT, the outcome data are particularly limited. We, therefore,
      conducted a retrospective single-institution study and report the outcomes and
      prognostic variables associated with overall survival (OS) and relapse in 43
      pediatric patients who underwent a second HCT between 2000 and 2013. Eleven of
      the 43 patients who underwent transplantation remain alive and disease-free at a
      median follow-up of 49 months (range, 5 to 127 months). The 5-year probability of
      OS for the entire cohort was 24%. Patients who had early relapse (<6 months)
      after first HCT had significantly worse OS than those who relapsed late (>6
      months), with 5-year OS at 11% versus 34%, respectively (hazard ratio [HR], 2.24;
      95% confidence interval [CI], 1.21 to 4.93; P = .013). Active disease at time of
      second HCT was also associated with a significantly increased risk of relapse
      (subdistribution hazard ratio [SHR], 2.36; P = .049) for the entire cohort and
      relapse was the most frequent cause of death (23 of 32; 72%). On subgroup
      analysis for the 34 patients with leukemia alone, presence of active disease was
      associated both with a significant decrease in OS (SHR, 2.28; 95% CI, 1.02 to
      5.09; P = .044) and significant increase in the rate of relapse (SHR, 2.46; P =
      .046). By contrast, underlying disease, donor source, conditioning regimen, or
      development of GVHD did not modify OS or rate of relapse. Hence, a second HCT
      appears to be a useful therapeutic option in children with relapsed hematological
      malignancies that is most likely to benefit those individuals with late onset of
      relapse and with low disease burden at the time of transplantation. 

PMID- 25765556
TI  - Short Course of Post-Transplantation Cyclophosphamide and Bortezomib for Graft
      versus-Host Disease Prevention after Allogeneic Peripheral Blood Stem Cell
      Transplantation Is Feasible and Yields Favorable Results: A Phase I Study.
AB  - An effective graft-versus-host disease (GVHD) preventative approach that
      preserves the graft-versus-tumor effect after allogeneic hematopoietic stem cell
      transplantation (HSCT) remains elusive. Standard GVHD prophylactic regimens
      suppress T cells indiscriminately and are suboptimal. Conversely, post
      transplantation high-dose cyclophosphamide selectively destroys proliferating
      alloreactive T cells, allows the expansion of regulatory T cells, and induces
      long-lasting clonal deletion of intrathymic antihost T cells. It has been
      successfully used to prevent GVHD after allogeneic HSCT. Bortezomib has antitumor
      activity on a variety of hematological malignancies and exhibits a number of
      favorable immunomodulatory effects that include inhibition of dendritic cells.
      Therefore, an approach that combines post-transplantation cyclophosphamide and
      bortezomib seems attractive. Herein, we report the results of a phase I study
      examining the feasibility and safety of high-dose post-transplantation
      cyclophosphamide in combination with bortezomib in patients undergoing allogeneic
      peripheral blood HSCT from matched siblings or unrelated donors after reduced
      intensity conditioning. Cyclophosphamide was given at a fixed dose (50 mg/kg on
      days +3 and +4). Bortezomib dose was started at .7 mg/m2, escalated up to 1.3
      mg/m2, and was administered on days 0 and +3. Patients receiving grafts from
      unrelated donors also received rabbit antithymocyte globulin. The combination was
      well tolerated and allowed prompt engraftment in all patients. The incidences of
      acute GVHD grades II to IV and grades III and IV were 20% and 6.7%, respectively.
      With a median follow-up of 9.1 months (range, 4.3 to 26.7), treatment-related
      mortality was 13.5% with predicted 2-year disease-free survival and overall
      survival of 55.7% and 68%, respectively. The study suggests that the combination
      of post-transplantation cyclophosphamide and bortezomib is feasible and may offer
      an effective and practical GVHD prophylactic regimen. The combination, therefore,
      merits further examination.

PMID- 25765557
TI  - The impact of electroconvulsive therapy on the tryptophan-kynurenine metabolic
      pathway.
AB  - BACKGROUND: There is still limited knowledge about the mechanism of action of
      electroconvulsive therapy (ECT) in the treatment of depression. Substantial
      evidence suggests a role for the immune-moderated tryptophan (TRP)-kynurenine
      (KYN) pathway in depression; i.e. a depression-associated disturbance in the
      balance between the TRP-KYN metabolites towards a neurotoxic process. We,
      therefore, aimed to investigate the impact of ECT treatment on the TRP-KYN
      pathway, in association with ECT-related alterations in depressive symptoms.
      METHOD: Twenty-three patients with unipolar or bipolar depression, treated with
      bilateral ECT twice a week were recruited. Blood serum samples, and depression
      scores using the Hamilton Depression Rating Scale-17 items (HDRS) as well as the
      Beck Depression Inventory (BDI) were collected repeatedly during the period of
      ECT and until 6 weeks after the last ECT session. TRP and KYN metabolites were
      analyzed in serum using the High Performance Liquid Chromatography. Four patients
      could not complete the study; thereby yielding data of 19 patients. Analyses were
      performed using multilevel linear regression analysis. RESULTS: There was an
      increase in kynurenic acid (KYNA) (B=0.04, p=0.001), KYN/TRP ratio (B=0.14,
      p=0.001), KYNA/KYN ratio (B=0.07, p<0.0001), and KYNA/3-hydroxykynurenine ratio
      (B=0.01, p=0.008) over time during the study period. KYN (B=-0.02, p=0.003) and
      KYN/TRP (B=-0.19, p=0.003) were negatively associated with total HDRS over time.
      Baseline TRP metabolite concentrations did not predict time to ECT response.
      CONCLUSION: Our findings show that ECT influences the TRP-KYN pathway, with a
      shift in TRP-KYN metabolites balance towards molecules with neuroprotective
      properties correlating with antidepressant effects of ECT; thereby providing a
      first line of evidence that the mechanism of action of ECT is (co)mediated by the
      TRP-KYN pathway.

PMID- 25765558
TI  - A protocol for chemical mutagenesis in Strongyloides ratti.
AB  - Genetic analysis using experimentally induced mutations has been a most valuable
      tool in the analysis of various organisms. However, genetic analysis of
      endoparasitic organisms tends to be difficult because of the limited
      accessibility of the sexually reproducing adults, which are normally located
      within the host. Nematodes of the genera Strogyloides and Parastrongyloides
      represent an exception to this because they can form facultative free-living
      sexually reproducing generations in between parasitic generations. Here we
      present a protocol for the chemical mutagenesis of Strongyloides ratti. Further
      we evaluate the feasibility of identifying the induced mutations by whole genome
      re-sequencing. 

PMID- 25765559
TI  - Changes in the locomotory and reproductive behavior of Biomphalaria glabrata
      infected with Schistosoma mansoni.
AB  - The infection and development of a parasite may cause physiological,
      morphological and behavioral changes in its host. Changes in the locomotory
      activity of a host induced by their parasites may also influence the life-cycles
      of both host and parasite in the environment. The aim of the present work was to
      evaluate the locomotory activities of Biomphalaria glabrata before and after an
      experimental infection with Schistosoma mansoni relating to the shedding of
      cercaria. In addition, the reproductive parameters of infected B. glabrata were
      analyzed during the prepatent and patent periods of the infection. The locomotory
      activity was recorded using an image analysis biomonitoring system based on a
      Videomex V. Five parameters were analyzed: 'Distance traveled', 'Ambulatory
      time', 'Stereotypic time', 'Resting time' and 'Average speed'. The number of shed
      cercariae was counted twice at 45 and 52 days post-infection. The reproductive
      parameters of infected B. glabrata analyzed were the numbers of egg masses, eggs
      and hatched snails. All statistical analyses were performed using the R program.
      Of the 69 snails infected with S. mansoni, 33 (47.8%) shed cercariae ('positive')
      and 36 (52.2%) ('exposed') failed to exhibit any cercarial shedding prior to the
      end of the experiment. The locomotory activity of the all snails increased
      significantly after infection with S. mansoni. However, when the 'positive' and
      'exposed' snails were compared, the former, shedding cercariae, were less motile.
      With regard to reproduction, 84.8% (28/33) of the 'positive' and 27.7% (10/36) of
      the 'exposed' snails failed to lay egg masses during patent period. The number of
      cercariae individually shed by each 'positive' snail presented a positive
      relation with 'Stereotypic time' and a negative relation with egg laying. Our
      findingshighlight the way in which infection with S. mansoni affects the
      locomotory and the reproductive behavior of B. glabrata. The number of cercariae
      shed is directly associated with the reduction/interruption in egg-laying and
      with an increase in random movement.

PMID- 25765560
TI  - Validation of cell-free culture using scanning electron microscopy (SEM) and gene
      expression studies.
AB  - A cell-free culture system for Cryptosporidium parvum was analysed using scanning
      electron microscopy (SEM) to characterise life cycle stages and compare gene
      expression in cell-free culture and cell culture using HCT-8 cells.
      Cryptosporidium parvum samples were harvested at 2 h, 8 h, 14 h, 26 h, 50 h, 74
      h, 98 h, 122 h and 170 h, chemically fixed and specimens were observed using a
      Zeiss 1555 scanning electron microscope. The presence of sporozoites,
      trophozoites and type I merozoites were identified by SEM. Gene expression in
      cell culture and cell-free culture was studied using reverse transcriptase
      quantitative PCR (RT-qPCR) of the sporozoite surface antigen protein (cp15), the
      glycoprotein 900 (gp900), the Cryptosporidium oocyst wall protein (COWP) and 18S
      ribosomal RNA (rRNA) genes in both cell free and conventional cell culture. In
      cell culture, cp15 expression peaked at 74 h, gp900 expression peaked at 74 h and
      98 h and COWP expression peaked at 50 h. In cell-free culture, CP15 expression
      peaked at 98 h, gp900 expression peaked at 74 h and COWP expression peaked at 122
      h. The present study is the first to compare gene expression of C. parvum in cell
      culture and cell-free culture and to characterise life cycle stages of C. parvum
      in cell-free culture using SEM. Findings from this study showed that gene
      expression patterns in cell culture and cell-free culture were similar but in
      cell-free culture, gene expression was delayed for CP15 and COWP in cell free
      culture compared with the cell culture system and was lower. Although three life
      cycle stageswere conclusively identified, improvements in SEM methodology should
      lead to the detection of more life cycle stages. 

PMID- 25765561
TI  - The role of biodegradable stents in the management of benign and malignant
      oesophageal strictures: A cohort study.
AB  - BACKGROUND: Oesophageal strictures can be caused by benign or malignant
      processes. Up to 10% of patients with a benign stricture are refractory to
      pneumatic dilatation and may benefit from biodegradable stent (BD) insertion.
      Biodegradable stents also have a role in malignant oesophageal strictures to
      facilitate enteral nutrition while staging or neo-adjuvant treatment is
      completed. The aim of this study was to review the safety and efficacy of BD
      stents in the management of benign or malignant oesophageal strictures. METHODS:
      A single centre retrospective cohort study was performed. Dysphagia was graded
      before and after stenting using a validated score. All patients were followed up
      for at least 30 days and all adverse events were recorded. RESULTS: Twenty eight
      stents were inserted in 20 patients; 11 for malignant and 17 for benign disease.
      One further attempted stenting was impossible due to a high benign stricture.
      There were no perforations and the 30-day mortality rate was zero. Mean dysphagia
      scores improved from 2.65 to 1.00 (p value <0.001) in benign disease and from
      3.27 to 1.36 (p value <0.001) in patients with malignant disease. Surgical
      resection was not compromised following stent insertion in the malignant group.
      CONCLUSIONS: Biodegradable stent insertion is a safe and efficacious adjunct in
      the treatment of benign and malignant oesophageal strictures. In malignant
      disease, BD stent insertion can maintain enteral nutrition while staging or neo
      adjuvant therapy is completed without adversely impacting on surgical resection.

PMID- 25765562
TI  - Falling-solid flash vacuum pyrolysis: an efficient preparation of arylacetylenes.
AB  - Automated falling-solid flash vacuum pyrolysis allows the rapid and efficient
      synthesis of a variety of arylacetylenes from 4-arylmethylidene-5(4H)-isoxazolone
      derivatives, which were prepared from aldehyde precursors. The acetylenes are
      readily obtained in multigram quantities. 

PMID- 25765563
TI  - Plasma vs heart tissue concentration in humans - literature data analysis of
      drugs distribution.
AB  - Little is known about the uptake of drugs into the human heart, although it is of
      great importance nowadays, when science desires to predict tissue level behavior
      rather than to measure it. Although the drug concentration in cardiac tissue
      seems a better predictor for physiological and electrophysiological changes than
      its level in plasma, knowledge of this value is very limited. Tissue to plasma
      partition coefficients (Kp) come to rescue since they characterize the
      distribution of a drug among tissues as being one of the input parameters in
      physiologically based pharmacokinetic (PBPK) models. The article reviews cardiac
      surgery and forensic medical studies to provide a reference for drug
      concentrations in human cardiac tissue. Firstly, the focus is on whether a drug
      penetrates into heart tissue at a therapeutic level; the provided values refer to
      antibiotics, antifungals and anticancer drugs. Drugs that directly affect
      cardiomyocyte electrophysiology are another group of interest. Measured levels of
      amiodarone, digoxin, perhexiline and verapamil in different sites in human
      cardiac tissue where the compounds might meet ion channels, gives an insight into
      how these more lipophilic drugs penetrate the heart. Much data are derived from
      postmortem studies and they provide insight to the cardiac distribution of more
      than 200 drugs. The analysis depicts potential problems in defining the active
      concentration location, what may indirectly suggest multiple mechanisms involved
      in the drug distribution within the heart. Copyright (c) 2015 John Wiley & Sons,
      Ltd.

PMID- 25765564
TI  - A new method for quantitative marking of deposited lithium by chemical treatment
      on graphite anodes in lithium-ion cells.
AB  - A novel approach for the marking of deposited lithium on graphite anodes from
      large automotive lithium-ion cells (>=6 Ah) is presented. Graphite anode samples
      were extracted from two different formats (cylindrical and pouch cells) of
      pristine and differently aged lithium-ion cells. The samples present a variety of
      anodes with various states of lithium deposition (also known as plating). A
      chemical modification was performed to metallic lithium deposited on the anode
      surface due to previous plating with isopropanol (IPA). After this procedure an
      oxygenated species was detected by scanning electron microscopy (SEM), which
      later was confirmed as Li2 CO3 by Fourier transform infrared spectroscopy (FTIR)
      and X-ray powder diffraction (XRPD). A valuation of the covered area by Li2 CO3
      was carried out with an image analysis using energy-dispersive X-ray spectroscopy
      (EDX) and quantitative Rietveld refinement. 

PMID- 25765565
TI  - Choledochoscopic high-frequency needle-knife electrotomy as an effective
      treatment for intrahepatic biliary strictures.
AB  - BACKGROUND AND AIM: Hepatolithiasis is associated with the presence of
      intrahepatic biliary strictures, and balloon dilatation is the main approach.
      However, this method is difficult to implement if the bile duct distal to the
      stricture is blocked by stones. Therefore, alternative methods need to be
      explored to effectively treat hepatolithiasis. The aim of this study is to
      investigate the feasibility and effectiveness of choledochoscopic high-frequency
      needle-knife electrotomy for the treatment of intrahepatic biliary strictures.
      METHODS: Clinical data of 58 patients suffering from intrahepatic bile duct
      strictures from January 2011 to January 2013 were retrospectively analyzed.
      Choledochoscopic electrotomy was used to resolve the strictures. RESULTS: One
      hundred thirty-four sites of intrahepatic bile duct strictures were discovered.
      The average operating time of electrotomy is 5.6 min (range, 1 ~ 15 min).
      Structured bile duct tissue bleeding occurred in eight sites (8/134, 6.0%) but
      were resolved by endoscopic high-frequency electric cautery. After the
      operations, 14 cases of cholangitis (14/58, 24.1%), three cases of delayed
      hemobilia, one case of liver abscess (1/58, 1.7%), and seven cases of stenting
      exodus (7/58, 12.1%) were observed despite conservative treatment and stenting
      reset. The average supporting time was 7.0 months (6 ~ 9 months). No abnormal
      bile duct structure or presence of stone was found according to choledochoscopy.
      The follow-up period ranged from 12 to 48 months. Hepatolithiasis recurred in
      five (5/58, 8.6%) patients, and the cumulative recurrent probability of
      intrahepatic bile duct stricture was 5.2% (7/134). CONCLUSIONS: Choledochoscopic
      high-frequency needle-knife electrotomy could be considered as a simple, safe,
      and effective complementary approach for treating intrahepatic biliary
      strictures.

PMID- 25765566
TI  - Empathy as a "risky strength": A multilevel examination of empathy and risk for
      internalizing disorders-CORRIGENDUM.

PMID- 25765568
TI  - Ligand field variations: tuning the toroidal moment of Dy6 rings.
AB  - Two new examples of Dy6 cyclic coordination clusters have been synthesised in
      order to discover how the toroidal moment in such a motif can be tuned and
      optimised. 

PMID- 25765569
TI  - Intraoperative distensibility measurement during laparoscopic Heller's myotomy
      for achalasia may reduce the myotomy length without compromising patient outcome.
AB  - Our study aimed to assess whether intraoperative esophagogastric junction (EGJ)
      distensibility measurement using the EndoFLIP EF325 catheter (Crospon Ltd.,
      Galway, Ireland) could potentially be used to guide laparoscopic Heller's myotomy
      (LHM), potentially modifying the operation outcome and comparing this clinically
      to our previous technique of gastroscopic assessment. Following a full diagnostic
      assessment with manometry and endoscopy patients with achalasia were divided into
      two groups. A retrospective cohort of patients operated on between 2007 and 2010
      had a gastroscopy-guided LHM (G-LHM) with a standardized myotomy of 8 cm on the
      esophagus and 3 cm on the stomach. From 2010, patients were prospectively studied
      with an EndoFLIP-guided LHM (E-LHM). The length of the myotomy was dictated by
      intraoperative distensibility monitoring of the EGJ. All patients with achalasia
      recorded Urbach quality of life scoring preoperatively and 6 months
      postoperatively. A further group of normal laparoscopic control patients (E-LC)
      without any esophageal pathology also underwent intraoperative EGJ distensibility
      monitoring. Thirty-eight patients took part, 15 in the E-LC group, 8 in G-LHM
      group and 15 in the E-LHM group. We revealed that patients with achalasia in the
      E-LHM group had a significantly smaller EGJ cross-sectional area and
      distensibility than the E-LC group. Myotomy and fundoplication increased the
      distensibility of the EGJ to a value greater than normal control patients.
      Patients in the G-LHM group had a standard myotomy of 11 cm; patients in the E
      LHM group had a variable length myotomy of 6 cm (IQR 5.0-6.0). In both G-LHM and
      E-LHM groups, there was a significant improvement in patient's quality of life
      with no significant difference between the groups. Our study has shown that the
      EndoFLIP system was effective at measuring distensibility changes during LHM. LHM
      significantly increases the distensibility of the EGJ and also significantly
      improves patient symptoms. E-LHM may reduce the overall myotomy length, and this
      does not appear to compromise the clinical outcome. 

PMID- 25765567
TI  - The TRPA1 channel mediates the analgesic action of dipyrone and pyrazolone
      derivatives.
AB  - BACKGROUND AND PURPOSE: Although still used by hundreds of millions of people
      worldwide, the mechanism of the analgesic action of the pyrazolone derivatives
      (PDs), dipyrone, propyphenazone and antipyrine remains unknown. The transient
      receptor potential ankyrin 1 (TRPA1) channel, expressed by nociceptors, is
      emerging as a major pain transduction pathway. We hypothesized that PDs target
      the TRPA1 channel and by this mechanism produce their analgesic effect.
      EXPERIMENTAL APPROACH: Calcium responses and currents were studied in cultured
      TRPA1-expressing rodent dorsal root ganglion neurons and human cells. Acute
      nociception and mechanical hypersensitivity were investigated in naive and
      genetically manipulated mice. KEY RESULTS: Pyrazolone and PDs selectively
      inhibited calcium responses and currents in TRPA1-expressing cells and acute
      nocifensor responses in mice evoked by reactive channel agonists (allyl
      isothiocyanate, acrolein and H2 O2 ). In line with recent results obtained with
      TRPA1 antagonists and TRPA1 gene deletion, the two most largely used PDs,
      dipyrone and propyphenazone, attenuated TRPA1-mediated nociception and mechanical
      allodynia in models of inflammatory and neuropathic pain (formalin, carrageenan,
      partial sciatic nerve ligation and the chemotherapeutic drug, bortezomib).
      Notably, dipyrone and propyphenazone attenuated carrageenan-evoked mechanical
      allodynia, without affecting PGE2 levels. The main metabolites of PDs did not
      target TRPA1 and did not affect TRPA1-dependent nociception and allodynia.
      CONCLUSIONS AND IMPLICATIONS: Evidence that in rodents the
      nociceptive/hyperalgesic effect produced by TRPA1 activation is blocked by PDs
      suggests that a similar pathway is attenuated by PDs in humans and that TRPA1
      antagonists could be novel analgesics, devoid of the adverse haematological
      effects of PDs.

PMID- 25765570
TI  - Characteristic findings on panoramic radiography and cone-beam CT to predict
      paresthesia after extraction of impacted third molar.
AB  - The purpose of this study was to compare findings on the relationship between
      impacted molar roots and the mandibular canal in panoramic and three-dimensional
      cone-beam CT (CBCT) images to identify those that indicated risk of postoperative
      paresthesia. The relationship between impacted molars and the mandibular canal
      was first classified using panoramic images. Only patients in whom the molar
      roots were either in contact with or superimposed on the canal were evaluated
      using CBCT. Of 466 patients examined using both panoramic and CBCT images, 280
      underwent surgical extraction of an impacted molar, and 15 of these (5%) reported
      postoperative paresthesia. The spatial relationship between the impacted third
      molar root and the mandibular canal was determined by examining para-sagittal
      sections (lingual, buccal, inter-radicular, inferior, and combinations) obtained
      from the canal to the molar root and establishing the proximity of the canal to
      the molar root (in contact with or without loss of the cortical border and
      separate). The results revealed that darkening of the roots with interruption of
      the mandibular canal on panoramic radiographs and the inter-radicular position of
      the canal in CBCT images were characteristic findings indicative of risk of
      postoperative paresthesia. These results suggest that careful surgical
      intervention is required in patients with the above characteristics. 

PMID- 25765571
TI  - Grinding efficiency of abutment tooth with both dentin and core composite resin
      on axial plane.
AB  - The purpose of this study was to evaluate grinding efficiency in abutment teeth
      comprising both dentin and core composite resin in the axial plane. Grinding was
      performed over 5 runs at two loads (0.5 or 0.25 N) and two feed rates (1 or 2
      mm/sec). The grinding surface was observed with a 3-D laser microscope.
      Tomographic images of the grinding surfaces captured perpendicular to the feed
      direction were also analyzed. Using a non-ground surface as a reference, areas
      comprising only dentin, both dentin and core composite resin, or only core
      composite resin were analyzed to determine the angle of the grinding surface.
      Composite resins were subjected to the Vickers hardness test and scanning
      electron microscopy. Data were statistically analyzed using a one-way analysis of
      variance and multiple comparison tests. Multiple regression analysis was
      performed for load, feed rate, and Vickers hardness of the build-up material
      depending on number of runs. When grinding was performed at a constant load and
      feed rate, a greater grinding angle was observed in areas comprising both dentin
      and composite resin or only composite resin than in areas consisting of dentin
      alone. A correlation was found between machinability and load or feed rate in
      areas comprising both dentin and composite resin or composite resin alone, with a
      particularly high correlation being observed between machinability and load.
      These results suggest that great caution should be exercised in a clinical
      setting when the boundary between the dentin and composite resin is to be ground,
      as the angle of the grinding surface changes when the rotating diamond point
      begins grinding the composite resin. 

PMID- 25765572
TI  - Estimated tooth loss based on number of present teeth in Japanese adults using
      national surveys of dental disease.
AB  - Oral health instruction for adults should take into account the potential effect
      of tooth loss, as this has been suggested to predict further tooth loss.
      Therefore, the purpose of this study was to determine whether further tooth loss
      could be predicted from the number of present teeth (PT). We employed the same
      method as in our previous study, this time using two national surveys of dental
      disease, which were deemed to represent a generational cohort. Percentiles were
      estimated using the cumulative frequency distribution of PT from the two surveys.
      The first was a survey of 704 participants aged 50-59 years conducted in 2005,
      and the second was a survey of 747 participants aged 56-65 years conducted in
      2011. The 1st to 100th percentiles of the number of PT were calculated for both
      age groups. Using these percentiles and a generational cohort analysis based on
      the two surveys, the number of teeth lost per year could be calculated. The
      distribution of number of teeth lost generated a convex curve. Peak tooth loss
      occurred at around 12-14 PT, with 0.54 teeth being lost per year. The percentage
      of teeth lost (per number of PT) increased as number of PT decreased. The results
      confirmed that tooth loss promotes further tooth loss. These data should be made
      available for use in adult oral health education. 

PMID- 25765573
TI  - Influence of hydrophilic pre-treatment on resin bonding to zirconia ceramics.
AB  - Atmospheric plasma or ultraviolet (UV) treatment alters the surface
      characteristics of tetragonal zirconia polycrystal (TZP), increasing its
      hydrophilicity by reducing the contact angle against water to zero. This suggests
      that such treatment would increase the wettability of bonding resin. The purpose
      of this study was to determine how increasing the hydrophilicity of TZP through
      plasma irradiation, UV treatment, or application of ceramic primer affected
      initial bonding with resin composites. Here, the effect of each pre-treatment on
      the hydrophilicity of TZP surfaces was determined by evaluating change in shear
      bond strength. Plasma irradiation, UV, or ceramic primer pre-treatment showed no
      significant effect on bonding strength between TZP surfaces and resin composites.
      In addition, alumina blasting yielded no significant increase in bond strength.
      Plasma irradiation, UV treatment, or ceramic primer pre-treatment did not lead to
      significant increase in bond strength between TZP and resin composites. 

PMID- 25765574
TI  - Case of cervical carcinoma of unknown primary treated through multidisciplinary
      approach.
AB  - Carcinoma of unknown primary (CUP) is where the primary site remains unidentified
      even though metastases are present, and accounts for 3-5% of all human
      malignancies. Here, we report a multidisciplinary approach to the treatment of a
      squamous cell CUP occurring in the left cervical region. Following radical
      surgery for carcinoma of the colon, swelling occurred in the left cervical region
      in a 59-year-old man. The results of an incisional biopsy indicated a diagnosis
      of squamous cell carcinoma (SCC), and he was referred to our department for
      examination. The primary carcinoma was not identifiable despite an extensive
      diagnostic workup including a physical examination, fiberoptic endoscopy,
      computed tomography, magnetic resonance imaging, and fluorodeoxyglucose F18
      positron emission tomography, resulting in a diagnosis of an SCC of unknown in
      the cervical region. The patient was initially treated with three cycles of
      docetaxel 75 mg/m(2)/day, cisplatin 100 mg/m(2)/day, and 5-fluorouracil 1,000
      mg/m(2)/day as induction chemotherapy. This was followed by concurrent
      chemoradiotherapy (cisplatin 30 mg/m(2)/day, 70 Gy) and neck dissection.
      Subsequent pathological examination revealed no vestiges of the tumor. The
      patient has remained free from recurrence and metastasis for 6 years. 

PMID- 25765575
TI  - A case of cystadenoma arising in the upper lip.
AB  - Cystadenoma, a common benign tumor derived from glandular tissue, generally
      occurs in the appendix, ovaries, kidney, or pancreas. While rare in the oral and
      maxillofacial region, they do sometimes occur in the parotid or minor salivary
      glands. We report a case of cystadenoma arising in the upper lip region. The
      patient was a 37-year-old woman referred to our hospital with a painless mass on
      the left upper lip initially found during treatment at a local dental clinic. The
      medical history was non-contributory. The 7*5-mm mass was well-defined, elastic,
      and flexible. The surface of the mucosa appeared healthy. The mass was clinically
      diagnosed as a benign tumor of the left upper lip. Because the tumor was painless
      and slow-growing, and magnetic resonance imaging suggested that it was benign,
      resection was performed under local anesthesia without biopsy.
      Histopathologically, cystadenoma was diagnosed. No signs of recurrence or
      metastasis have been seen as of 24 months postoperatively and the progress of the
      patient has been satisfactory. 

PMID- 25765576
TI  - Effect of collaborative intervention by medical and dental professionals on
      adherence to smoking abstinence.
AB  - The need for smoking cessation care is widely recognized. It is, however,
      difficult to achieve continued smoking abstinence, even when cessation has
      initially been achieved. The aim of this study was to determine the effectiveness
      of a collaborative smoking cessation program involving both medical and dental
      professionals on smoking abstinence. A total of 10 patients visiting our Smoking
      Cessation Outpatient Clinic were followed up and monitored for smoking
      abstinence. All received smoking cessation care consisting mainly of counseling
      by dental and medical professionals and pharmacotherapy. They also concurrently
      received an oral examination, instruction on oral hygiene, and professional tooth
      cleaning. The 4-week smoking abstinence rate was 90.0% on completion of the
      program. One patient failed to complete the program. At one month after the
      program, 8 out of 9 patients remained abstinent (4-month abstinence; 88.9%). At 3
      months after the program, 7 patients remained abstinent (6-month abstinence;
      77.8%). Follow-up was impossible in one patient. Within the limitations of the
      present study, it is suggested that such collaborative intervention including
      subsequent dental care has the potential to promote short-term adherence to
      smoking abstinence. 

PMID- 25765577
TI  - Sex- and age-based differences in single tooth loss in adults.
AB  - The aim of this study was to investigate sex- and age-based differences in single
      tooth loss in adults. The data were obtained from the results of a periodontal
      disease examination carried out under a health promotion law in a city in Japan
      in 2005. Baseline data from a total of 3,872 participants aged 40 or 60 years
      comprising 1,302 men and 2,570 women were available. Only participants with 27
      present teeth were eligible for inclusion in the analysis, giving a total of 218
      men and 428 women. Third molars were excluded from the study. The bilateral total
      of each type of tooth was obtained. The mandibular first molar was missing in
      26.7% of the men and 36.2% of the women among 40-year-olds and 35.3% of the men
      and 29.8% of the women among 60-year-olds. The mandibular second molar was
      missing in 14.7% of the men and 12.5% of the women among 40-year-olds, and 17.6%
      of the men and 18.4% of the women among 60-year-olds. Significant differences
      were observed between men and women in the mandibular second premolars and first
      molars among 40-year-olds. These results suggest that we need to pay more
      attention to individual teeth which are at particularly high risk for tooth loss,
      namely the mandibular first and second molars, and especially the mandibular
      first molars in middle-aged women. 

PMID- 25765578
TI  - p16 Gene Transfer Induces Centrosome Amplification and Abnormal Nucleation
      Associated with Survivin Downregulation in Glioma Cells.
AB  - OBJECTIVE: In human glioma cells, p16 gene transfer induced G1/S arrest,
      increased radiosensitivity and abnormal nucleation (especially bi- and
      multinucleation). Survivin suppression caused G2/M arrest, radiosensitization and
      an increase in aneuploidy accompanied by centrosome amplification. Abnormal
      nucleation and aneuploidy represent chromosome instability (CIN), and it is well
      known that centrosome amplification leads to CIN. However, little has been
      reported that suggests that transferring p16 causes centrosome overduplication
      during the G1/S phase. METHODS: The p16 gene was transferred into p16-null human
      glioma cell lines (U251MG and D54MG) using adenovirus with or without
      irradiation. Centrosome amplification was evaluated by immunofluorescence. We
      also investigated the DNA replication licensing factor CDT1, its inhibitor
      geminin and survivin expression as regulators of chromosomal segregation.
      RESULTS: p16 gene transfer with radiation initiated the greatest degree of
      centrosome overduplication. CDT1 showed low levels, geminin was unchanged and
      survivin decreased in Ax-hp16-infected cells with radiation. Those changes of
      factors affecting DNA licensing or chromosomal segregation might contribute to
      CIN. CONCLUSION: p16 transfer caused centrosome amplification even in G1/S phase
      arrested cells. This suggests that p16 is involved in abnormal nucleation and
      radiosensitization in human glioma cells. (c) 2015 S. Karger AG, Basel.

PMID- 25765579
TI  - High-yield production of vanillin from ferulic acid by a coenzyme-independent
      decarboxylase/oxygenase two-stage process.
AB  - Vanillin is one of the world's most important flavor and fragrance compounds in
      foods and cosmetics. Recently, we demonstrated that vanillin could be produced
      from ferulic acid via 4-vinylguaiacol in a coenzyme-independent manner using the
      decarboxylase Fdc and the oxygenase Cso2. In this study, we investigated a new
      two-pot bioprocess for vanillin production using the whole-cell catalyst of
      Escherichia coli expressing Fdc in the first stage and that of E. coli expressing
      Cso2 in the second stage. We first optimized the second-step Cso2 reaction from 4
      vinylguaiacol to vanillin, a rate-determining step for the production of
      vanillin. Addition of FeCl2 to the cultivation medium enhanced the activity of
      the resulting E. coli cells expressing Cso2, an iron protein belonging to the
      carotenoid cleavage oxygenase family. Furthermore, a butyl acetate-water biphasic
      system was effective in improving the production of vanillin. Under the optimized
      conditions, we attempted to produce vanillin from ferulic acid by a two-pot
      bioprocess on a flask scale. In the first stage, E. coli cells expressing Fdc
      rapidly decarboxylated ferulic acid and completely converted 75 mM of this
      substrate to 4-vinylguaiacol within 2 h at pH 9.0. After the first-stage
      reaction, cells were removed from the reaction mixture by centrifugation, and the
      pH of the resulting supernatant was adjusted to 10.5, the optimal pH for Cso2.
      This solution was subjected to the second-stage reaction. In the second stage, E.
      coli cells expressing Cso2 efficiently oxidized 4-vinylguaiacol to vanillin. The
      concentration of vanillin reached 52 mM (7.8 g L(-1)) in 24 h, which is the
      highest level attained to date for the biotechnological production of vanillin
      using recombinant cells.

PMID- 25765580
TI  - Enhancement of recombinant human serum albumin in transgenic rice cell culture
      system by cultivation strategy.
AB  - Fusion of the sugar-starvation-induced alphaAmy3 promoter with its signal peptide
      has enabled secretion of recombinant human serum albumin (rHSA) into the culture
      medium. To simplify the production process and increase the rHSA yield in rice
      suspension cells, a one-step strategem without medium change was adopted. The
      yield of rHSA was increased sixfold by this one-step approach compared with the
      two-step recombinant protein process, in which a change of the culture medium to
      sugar-free medium is required. The one-step strategem was applied to check
      repeated cycle of rHSA production, and the production of rHSA was also higher in
      each cycle in the one-step, as opposed to the two-step, production process. The
      use of the one-step process resulted in fewer damaged cells during the cell sugar
      starvation phase for recombinant protein production. Furthermore, we scaled up
      the rHSA production in a 2-L airlift and a 2-L stirred tank bioreactor by the one
      step approach, and concluded that rHSA can be enriched to 45 mg L(-1) in plant
      culture commonly used MS medium by the airlift-type bioreactor. Our results
      suggest that rHSA production can be enriched by this optimized cultivation
      strategem.

PMID- 25765581
TI  - [Positron emission tomography in primary brain lymphoma: Diagnostic and
      prognostic significance].

PMID- 25765582
TI  - [Total knee prosthesis. Development of an objective selection tool for patients].

PMID- 25765583
TI  - Enzyme immunoassays as screening tools for catalysts and reaction discovery.
AB  - Enzyme immunoassays are incredibly powerful analytical tools for the quantifiable
      detection of target molecules in complex media. These techniques, which exploit
      the fantastic specific binding properties of antibodies, are fast, precise,
      selective and highly sensitive and thus perfectly adapted to high-throughput
      detection of important analytes. Although immunoassays have been used routinely
      by biologists for more than 50 years, especially for diagnostic purposes, it is
      only recently that chemists have used them to address pure chemical problems. In
      this feature article, we provide an overview of progress in the development of
      immunoassays and their use in two main fields of organic chemistry: the
      identification of efficient catalysts in libraries and the discovery of new
      chemical reactions. 

PMID- 25765584
TI  - Patterns and drivers of intraspecific variation in avian life history along
      elevational gradients: a meta-analysis.
AB  - Elevational gradients provide powerful natural systems for testing hypotheses
      regarding the role of environmental variation in the evolution of life-history
      strategies. Case studies have revealed shifts towards slower life histories in
      organisms living at high elevations yet no synthetic analyses exist of
      elevational variation in life-history traits for major vertebrate clades. We
      examined (i) how life-history traits change with elevation in paired populations
      of bird species worldwide, and (ii) which biotic and abiotic factors drive
      elevational shifts in life history. Using three analytical methods, we found that
      fecundity declined at higher elevations due to smaller clutches and fewer
      reproductive attempts per year. By contrast, elevational differences in traits
      associated with parental investment or survival varied among studies. High
      elevation populations had shorter and later breeding seasons, but longer
      developmental periods implying that temporal constraints contribute to reduced
      fecundity. Analyses of clutch size data, the trait for which we had the largest
      number of population comparisons, indicated no evidence that phylogenetic history
      constrained species-level plasticity in trait variation associated with
      elevational gradients. The magnitude of elevational shifts in life-history traits
      were largely unrelated to geographic (altitude, latitude), intrinsic (body mass,
      migratory status), or habitat covariates. Meta-population structure,
      methodological issues associated with estimating survival, or processes shaping
      range boundaries could potentially explain the nature of elevational shifts in
      life-history traits evident in this data set. We identify a new risk factor for
      montane populations in changing climates: low fecundity will result in lower
      reproductive potential to recover from perturbations, especially as fewer than
      half of the species experienced higher survival at higher elevations. 

PMID- 25765585
TI  - Effects of CO2 dissolution on phase distribution and degradation of dimethyl
      disulfide in soils under grape production.
AB  - BACKGROUND: Dimethyl disulfide (DMDS) is a fumigant recently registered in parts
      of the United States. The fumigant has high pesticidal activity, but does not
      disperse in soils as well as other fumigants. This study assessed the use of CO2
      as a propellant to improve soil dispersion and diffusion by evaluating the
      partitioning and degradation of DMDS after carbonation in four vineyard soils
      collected in California. RESULTS: The soil with the highest organic carbon
      content (Clarksburg) had the highest soil-water partition coefficient (Kd ) (P <
      0.001), which increased after carbonation. However, DMDS sorption decreased in
      the Mecca and Fowler soils. Henry's law constant (Kh ), which measures a
      compound's potential for partitioning between air and water, doubled from 0.04 to
      0.10 with the addition of CO2 , indicating less DMDS solubility. Carbonation did
      not negatively affect DMDS's half-lives in the different soils. CONCLUSION: While
      trials are needed for validation of field-scale impacts, carbonation had mixed
      effects on soil partitioning and no discernable impact on degradation, but
      greatly decreased DMDS water solubility. This indicates that carbonation could
      improve some facets of DMDS diffusion and dispersion, depending on soil
      properties (carbon content and moisture), without greatly affecting its other
      behaviors.

PMID- 25765586
TI  - The mature anther-preferentially expressed genes are associated with pollen
      fertility, pollen germination and anther dehiscence in rice.
AB  - BACKGROUND: The anthers and pollen grains are critical for male fertility and
      hybrid rice breeding. The development of rice mature anther and pollen consists
      of multiple continuous stages. However, molecular mechanisms regulating mature
      anther development were poorly understood. RESULTS: In this study, we have
      identified 291 mature anther-preferentially expressed genes (OsSTA) in rice based
      on Affymetrix microarray data. Gene Ontology (GO) analysis indicated that OsSTA
      genes mainly participated in metabolic and cellular processes that are likely
      important for rice anther and pollen development. The expression patterns of
      OsSTA genes were validated using real-time PCR and mRNA in situ hybridizations.
      Cis-element identification showed that most of the OsSTA genes had the cis
      elements responsive to phytohormone regulation. Co-expression analysis of OsSTA
      genes showed that genes annotated with pectinesterase and calcium ion binding
      activities were rich in the network, suggesting that OsSTA genes could be
      involved in pollen germination and anther dehiscence. Furthermore, OsSTA RNAi
      transgenic lines showed male-sterility and pollen germination defects.
      CONCLUSIONS: The results suggested that OsSTA genes function in rice male
      fertility, pollen germination and anther dehiscence and established molecular
      regulating networks that lay the foundation for further functional studies.

PMID- 25765587
TI  - Trends in utilization of specialty care centers in California for adults with
      congenital heart disease.
AB  - The American College of Cardiology and American Heart Association guidelines
      recommend that management of adult congenital heart disease (ACHD) be coordinated
      by specialty ACHD centers and that ACHD surgery for patients with moderate or
      complex congenital heart disease (CHD) be performed by surgeons with expertise
      and training in CHD. Given this, the aim of this study was to determine the
      proportion of ACHD surgery performed at specialty ACHD centers and to identify
      factors associated with ACHD surgery being performed outside of specialty
      centers. This retrospective population analysis used California's Office of
      Statewide Health Planning and Development's discharge database to analyze ACHD
      cardiac surgery (in patients 21 to 65 years of age) in California from 2000 to
      2011. Designation as a "specialty ACHD center" was defined on the basis of a
      national ACHD directory. A total of 4,611 ACHD procedures were identified. The
      proportion of procedures in patients with moderate and complex CHD delivered at
      specialty centers increased from 46% to 71% from 2000 to 2011. In multivariate
      analysis among those discharges for ACHD surgery in patients with moderate or
      complex CHD, performance of surgery outside a specialty center was more likely to
      be associated with patients who were older, Hispanic, insured by health
      maintenance organizations, and living farther from a specialty center. In
      conclusion, although the proportion of ACHD surgery for moderate or complex CHD
      being performed at specialty ACHD centers has been increasing, 1 in 4 patients
      undergo surgery at nonspecialty centers. Increased awareness of ACHD care
      guidelines and of the patient characteristics associated with differential access
      to ACHD centers may help improve the delivery of appropriate care for all adults
      with CHD. 

PMID- 25765588
TI  - Programming implantable cardioverter-defibrillator therapy zones to high ranges
      to prevent delivery of inappropriate device therapies in patients with primary
      prevention: results from the RISSY-ICD (Reduction of Inappropriate ShockS bY
      InCreaseD zones) trial.
AB  - Inappropriate shock is a frequently seen clinical problem despite advanced
      technologies used in modern implantable cardioverter-defibrillator (ICD) devices.
      Our aim was to investigate whether simply raising the ICD detection zones can
      decrease inappropriate therapies while still providing appropriate therapy. We
      randomized 223 patients with primary prevention to either the conventional
      programming group with 3 zones as VT1 (167 to 182 beats/min) with discriminators,
      VT2 (182 to 200 beats/min) with discriminators, and ventricular fibrillation
      (>200 beats/min) (n=100) or the high-zone programming group with 3 zones as VT1
      (171 to 200 beats/min) with discriminators, VT2 (200 to 230 beats/min) with
      discriminators, and ventricular fibrillation (>230 beats/min; n=101). Twenty-two
      patients were lost to follow-up. The primary objectives were the first episode of
      appropriate and inappropriate therapies. The secondary objectives were all-cause
      mortality and hospitalization for heart failure. During 12-month follow-up, the
      first episode of appropriate therapy was higher (22% vs 10%, hazard ratio [HR]
      2.18, 95% confidence interval [CI], 1.09 to 4.36, p=0.028) and the first episode
      of inappropriate therapy was lower (5% vs 28%, HR 0.18 [95% CI 0.07 to 0.44],
      p<0.001) in the high-zone group compared with the conventional group. Although
      all-cause mortality did not differ (2% for the high-zone group vs 3% for the
      conventional group, HR 0.65 [95% CI 0.11 to 3.99], p>0.05), hospitalization for
      heart failure was significantly higher in the conventional group (13% vs 4%, HR
      0.28 [95% CI 0.09 to 0.88], p=0.021). In conclusion, in a real-world population,
      high-zone settings of the single-, dual-, and triple-chamber ICDs were associated
      with reduction in inappropriate therapy while still providing appropriate
      therapy.

PMID- 25765589
TI  - Relation of reduced preclinical left ventricular diastolic function and cardiac
      remodeling in overweight youth to insulin resistance and inflammation.
AB  - Insulin resistance (IR) and inflammation are associated with an increased risk of
      cardiovascular disease and may contribute to obesity cardiomyopathy. The earliest
      sign of obesity cardiomyopathy is impaired left ventricular (LV) diastolic
      function, which may be evident in obese children and adolescents. However, the
      precise metabolic basis of the impaired LV diastolic function remains unknown.
      The aims of this study were to evaluate cardiac structure and LV diastolic
      function by tissue Doppler imaging in overweight and obese (OW) youth and to
      assess the relative individual contributions of adiposity, IR, and inflammation
      to alterations in cardiac structure and function. We studied 35 OW (body mass
      index standard deviation score 2.0+/-0.8; non-IR n=19, IR n=16) and 34 non-OW
      youth (body mass index standard deviation score 0.1+/-0.7). LV diastolic function
      was reduced in OW youth compared with non-OW controls, as indicated by lower peak
      myocardial relaxation velocities (p<0.001) and greater filling pressures
      (p<0.001). OW youth also had greater LV mass index (p<0.001), left atrial volume
      index, and LV interventricular septal thickness (LV-IVS; both p=0.02). IR-OW
      youth had the highest LV filling pressures, LV-IVS, and relative wall thickness
      (all p<0.05). Homeostasis model of assessment-insulin resistance and C-reactive
      protein were negative determinants of peak myocardial relaxation velocity and
      positive predictors of filling pressure. Adiponectin was a negative determinant
      of LV-IVS, independent of obesity. In conclusion, OW youth with IR and
      inflammation are more likely to have adverse changes to cardiovascular structure
      and function which may predispose to premature cardiovascular disease in
      adulthood.

PMID- 25765590
TI  - Comparison of the usefulness of enoxaparin versus warfarin for prevention of left
      ventricular mural thrombus after anterior wall acute myocardial infarction.
AB  - Left ventricular (LV) thrombus is one of the most common complications in
      patients with anterior acute myocardial infarction (AMI) and LV dysfunction.
      Although anticoagulation is frequently prescribed, data regarding the appropriate
      drug, duration, risks, and effect on echocardiographic indices of thrombus are
      lacking. Moreover, given the difficulty in obtaining adequate anticoagulation
      with warfarin, it is possible that short-term treatment with a more predictable
      agent would be effective. We randomized 60 patients at high risk of developing LV
      mural thrombus (anterior acute myocardial infarction with Q waves and ejection
      fraction<=40%) to receive either enoxaparin 1 mg/kg (maximum 100 mg)
      subcutaneously every 12 hours for 30 days or traditional anticoagulation
      (intravenous heparin followed by oral warfarin for 3 months). Clinical
      evaluations and transthoracic echocardiograms were obtained at baseline, in
      hospital, and at 3.5 months. There were no differences between the groups
      regarding baseline demographics, acute echocardiographic findings, and in
      hospital outcomes. The length of hospital stay tended to be shorter for the
      enoxaparin group (4.6 vs 5.6; p=0.066) and the corresponding hospital costs
      ($25,837 vs $34,666; p=0.18). At 3 months, bleeding and thromboembolic events
      were rare and similar between enoxaparin and warfarin groups. Although more
      patients had probable mural thrombus in the enoxaparin group compared with
      warfarin at 3.5 months (15% vs 4%; p=0.35), this was not significantly different.
      In conclusion, the use of enoxaparin tends to shorten hospitalization and lower
      cost of care. However, at 3.5 months, there appears to be numerically higher (but
      statistically insignificant) rates of LV thrombus in the enoxaparin group.

PMID- 25765591
TI  - Can on-admission electrocardiogram tell you which patients with ST-elevation
      myocardial infarction will develop ventricular fibrillation?

PMID- 25765592
TI  - CCL2/CCR2-dependent recruitment of Th17 cells but not Tc17 cells to the lung in a
      murine asthma model.
AB  - BACKGROUND: Interleukin (IL)-17 has been implicated in the pathogenesis of asthma
      and the progression of airway inflammation. Here, we used a model of allergic
      asthma and found that the frequencies of IL-17-secreting T helper (Th)17 and CD8
      (Tc)17 cells were both significantly increased, as was the expression of the CC
      chemokine receptor (CCR2) on the surface of these cells. CC chemokine ligand 2
      (CCL2) has been shown to mediate the activation and recruitment of inflammatory
      cells in asthma, which are also skewed after ovalbumin (OVA) challenge. However,
      the role of CCL2 on Th17 cells and Tc17 cells in asthma has not been illuminated.
      METHODS: Mice that were sensitized and challenged with OVA received anti-CCL2
      antibody (Ab; 5 MUg/day intratracheally) or CCR2 antagonist (RS504393, 2
      mg/kg/day intraperitoneally) prior to the challenge. Some mice received an
      isotype control Ab or vehicle alone. We then assessed the effects of allergic
      asthma and anti-CCL2 Ab or CCR2 antagonist treatment on the levels of IL-17 and
      CCL2, the Th17 and Tc17 cell frequencies and lung tissue inflammation. RESULTS:
      We demonstrated that CCL2 and IL-17 levels and the frequency of Th17 and Tc17
      cells in lung tissues and bronchoalveolar lavage fluid increased in the asthma
      group compared with the normal control mice. Blocking the CCL2/CCR2 axis greatly
      reduced the Th17 but not the Tc17 cell frequency, and revealed a suppressive
      effect on airway inflammation. CONCLUSION: These findings indicate a role for the
      CCL2/CCR2 axis in mediating Th17 but not Tc17 cell migration during acute
      allergic airway inflammation.

PMID- 25765594
TI  - Predictors of continuous tobacco smoking in a clinical cohort study of Danish
      laryngeal cancer patients smoking before treated with radiotherapy.
AB  - BACKGROUND: Many cancer patients who are smokers when starting cancer therapy
      continue smoking despite evidence of tobacco smoking as a risk factor for poor
      treatment response and secondary primary cancers. Small samples and inconsistent
      results in previous studies warrant further research to identify predictors of
      being a continuous smoker during and after radiotherapy. MATERIAL AND METHODS: In
      the clinical database of the Danish Head and Neck Cancer Group (DAHANCA), we
      identified 1455 patients diagnosed with laryngeal cancer between 2000 and 2010,
      who were all smokers at date of diagnosis and treated with primary radiotherapy.
      Information on the socio-economic characteristics of the study cohort was
      obtained from Statistics Denmark the year prior to diagnosis. Logistic regression
      analyses were applied. RESULTS: In the cohort of laryngeal cancer patients
      smoking before starting radiotherapy, 50% still smoked one year after
      radiotherapy similar to the percentage of smokers during treatment. Being younger
      than 60 years (OR 1.39, 95% CI 1.00-1.91), commenced smoking before the age of 15
      (OR 1.77, 95% CI 1.32-2.38), having a poor WHO Performance status (OR 3.09, 95%
      CI 1.71-5.61), low income (OR 2.21, 95% CI 1.23-3.98) and living alone (OR 1.56,
      95% CI 1.13-2.14) were associated with increased risk of continuous smoking
      during treatment. Similar findings were found two months and one year after
      radiotherapy, however, no association with living alone (OR 1.08, 95% CI 0.73
      1.59) at the one-year follow-up. Tumor stage and the average number of cigarettes
      smoked per day before radiotherapy were not associated with being a continuous
      smoker. CONCLUSION: Younger patients, who had an early smoking initiation, a poor
      performance status, low income and lived alone, were most likely to continue
      smoking. Continuous smoking was not related to the extent of disease.

PMID- 25765593
TI  - Neural systems mediating decision-making and response inhibition for social and
      nonsocial stimuli in autism.
AB  - Autism is marked by impairments in social reciprocity and communication, along
      with restricted, repetitive and stereotyped behaviors. Prior studies have
      separately investigated social processing and executive function in autism, but
      little is known about the brain mechanisms of cognitive control for both
      emotional and nonemotional stimuli. We used functional magnetic resonance imaging
      to identify differences in neurocircuitry between individuals with high
      functioning autism (HFA) and neurotypical controls during two versions of a go/no
      go task: emotional (fear and happy faces) and nonemotional (English letters).
      During the letter task, HFA participants showed hypoactivation in the ventral
      prefrontal cortex. During the emotion task, happy faces elicited activation in
      the ventral striatum, nucleus accumbens and anterior amygdala in neurotypical,
      but not HFA, participants. Response inhibition for fear faces compared with happy
      faces recruited occipitotemporal regions in HFA, but not neurotypical,
      participants. In a direct contrast of emotional no-go and letter no-go blocks,
      HFA participants showed hyperactivation in extrastriate cortex and fusiform
      gyrus. Accuracy for emotional no-go trials was negatively correlated with
      activation in fusiform gyrus in the HFA group. These results indicate that autism
      is associated with abnormal processing in socioemotional brain networks, and
      support the theory that autism is marked by a social motivational deficit. 

PMID- 25765595
TI  - Vascular effects of oxysterols and oxyphytosterols in apoE -/- mice.
AB  - OBJECTIVES: The aim of our study was to investigate vascular effects of
      oxysterols and oxyphytosterols on reactive oxygen species (ROS), endothelial
      progenitor cells, endothelial function and atherogenesis. METHODS: Male apoE-/
      mice were treated with cholesterol, sitosterol, 7-beta-OH-cholesterol, 7-beta-OH
      sitosterol, or cyclodextrin by daily intraperitoneal application. The respective
      concentrations in the plasma and in the arterial wall were determined by gas
      chromatography-flame ionization or mass spectrometry. ROS production was assessed
      by electron-spin resonance spectroscopy in the aorta, endothelial function of
      aortic rings and atherosclerosis in the aortic sinus was quantitated after 4
      weeks. RESULTS: Compared to vehicle, there was no difference in plasma
      cholesterol levels and arterial wall concentrations after i.p. application of
      cholesterol. 7-beta-OH-cholesterol concentrations were increased in the plasma
      (33.7+/-31.5 vs. 574.57.2+/-244.92 ng/ml) but not in the arterial wall (60.1+/
      60.1 vs. 59.3+/-18.2 ng/mg). Sitosterol (3.39+/-0.96 vs. 8.16+/-4.11 mg/dL;
      0.08+/-0.04 vs. 0.16+/-0.07 MUg/mg, respectively) and 7-beta-OH-sitosterol
      concentrations (405.1+/-151.8 vs. 7497+/-3223 ng/ml; 0.24+/-0.13 vs. 16.82+/
      11.58 ng/mg, respectively) increased in the plasma and in the aorta. The i.p
      application of the non-oxidized cholesterol or sitosterol did not induce an
      increase of plasma oxysterols or oxyphytosterols concentrations. Oxidative stress
      in the aorta was increased in 7-beta-OH-sitosterol treated mice, but not in mice
      treated with cholesterol, sitosterol, or 7-beta-OH-cholesterol. Moreover,
      cholesterol, sitosterol, 7-beta-OH-cholesterol, and 7-beta-OH-sitosterol did not
      affect endothelial-dependent vasodilation, or early atherosclerosis. CONCLUSION:
      Increased oxyphytosterol concentrations in plasma and arterial wall were
      associated with increased ROS production in aortic tissue, but did not affect
      endothelial progenitor cells, endothelial function, or early atherosclerosis.

PMID- 25765597
TI  - Lurasidone for schizophrenia.
AB  - Lurasidone (Latuda-Sunovion) is a new oral second-generation antipsychotic
      licensed for treating adults with schizophrenia. Although less likely to cause
      extrapyramidal adverse effects than first-generation antipsychotics, some second
      generation antipsychotics cause weight gain that may increase the risk of
      diabetes, hypertension and raised lipid levels.1,2 Lurasidone is promoted as
      offering a balance between efficacy and tolerability, with reported negligible
      effects on weight and minimal effects on glucose and cholesterol.3 Here we review
      evidence for lurasidone's efficacy and safety, and consider how it compares with
      other antipsychotics.

PMID- 25765598
TI  - Why drug shortages occur.
AB  - Drug shortages are recognised as being an important global issue1 that cause
      significant problems by delaying, and in some cases even preventing access to
      essential medicines.2 In the UK, problems caused by drug shortages have led to an
      enquiry by the All-Party Pharmacy Group (APPG)3,4 and publication of best
      practice guidance by the Department of Health (DH) working in conjunction with
      the manufacturers of branded and generic medicines.5-8 Widespread shortages of
      medicines commonly prescribed in primary care are now a regular occurrence and
      have significant impact on patients and healthcare professionals. In this article
      we discuss the reasons why shortages occur, how shortages are being addressed at
      a national and international level and what actions need to be taken to help
      minimise the impact on patients. 

PMID- 25765596
TI  - Diosgenin inhibits atherosclerosis via suppressing the MiR-19b-induced
      downregulation of ATP-binding cassette transporter A1.
AB  - RATIONALE: Diosgenin (Dgn), a structural analogue of cholesterol, has been
      reported to have the hypolipidemic and antiatherogenic properties, but the
      underlying mechanisms are not fully understood. Given the key roles of
      macrophages in cholesterol metabolism and atherogenesis, it is critical to
      investigate macrophage cholesterol efflux and development of atherosclerotic
      lesion after Dgn treatment. OBJECTIVE: This study was designed to evaluate the
      potential effects of Dgn on macrophage cholesterol metabolism and the development
      of aortic atherosclerosis, and to explore its underlying mechanisms. METHODS AND
      RESULTS: Dgn significantly up-regulated the expression of ATP-binding cassette
      transporter A1 (ABCA1) protein, but didn't affect liver X receptor alpha levels
      in foam cells derived from human THP-1 macrophages and mouse peritoneal
      macrophages (MPMs) as determined by western blotting. The miR-19b levels were
      markedly down-regulated in Dgn-treated THP-1 macrophages/MPM-derived foam cells.
      Cholesterol transport assays revealed that treatment with Dgn alone or together
      with miR-19b inhibitor notably enhanced ABCA1-dependent cholesterol efflux,
      resulting in the reduced levels of total cholesterol, free cholesterol and
      cholesterol ester as determined by high-performance liquid chromatography. The
      fecal 3H-sterol originating from cholesterol-laden MPMs was increased in
      apolipoprotein E knockout mice treated with Dgn or both Dgn and antagomiR-19b.
      Treatment with Dgn alone or together with antagomiR-19b elevated plasma high
      density lipoprotein levels, but reduced plasma low-density lipoprotein levels.
      Accordingly, aortic lipid deposition and plaque area were reduced, and collagen
      content and ABCA1 expression were increased in mice treated with Dgn alone or
      together with antagomiR-19b. However, miR-19b overexpression abrogated the lipid
      lowering and atheroprotective effects induced by Dgn. CONCLUSION: The present
      study demonstrates that Dgn enhances ABCA1-dependent cholesterol efflux and
      inhibits aortic atherosclerosis progression by suppressing macrophage miR-19b
      expression.

PMID- 25765599
TI  - Anatomical study of the course of the inferior alveolar nerve in craniofacial
      microsomia using three-dimensional computed tomography: correlation with the
      Pruzansky classification.
AB  - Dysmorphogenesis of the mandible complicates assessment of the course of the
      inferior alveolar nerve in patients with craniofacial microsomia. Our aim in the
      present study was to correlate the anatomical description of the course with the
      Pruzansky classification (which indicates the severity of hemifacial microsomia),
      in the mandibles of 22 affected patients using 3-dimensional computed tomography
      (CT). We measured the distance between fixed landmarks on the normal and the
      microsomic sides. The normal sides served as controls. In the group of five
      patients with type I disease, we found no significant differences between the
      unaffected and the microsomic side. In the nine patients with Pruzansky type II
      disease morphological views of the course showed a between-side difference in the
      length of the bony canal and the height of the mandibular ramus. In the five
      patients with Pruzansky type III disease, there was no bony canal. Three
      dimensional CT analysis may be of value in plotting the course of the inferior
      alveolar nerve and assisting the surgeon in mandibular osteotomy or distraction
      osteogenesis. 

PMID- 25765600
TI  - Shaping the fibula without fumbling: the SynpliciTi customised guide-plate.

PMID- 25765601
TI  - Woody hardness - a novel classification for the radiotherapy-treated neck.
AB  - The term 'woody neck' is widely used by surgeons and oncologists to describe the
      fibrosis that can occur following radiotherapy for head and neck malignancy.
      These soft tissue and skin changes can be compounded by neck dissection, either
      before or after radiotherapy. To our knowledge, there is no classification
      published in the literature to describe the degree of woody hardness following
      treatment. We propose a simple ABC classification for varying degrees of
      indurated oedema and neck fibrosis secondary to radiotherapy or long-standing
      pathology, using the hardness of different woods to enable a suitable description
      to be made of severity. 

PMID- 25765602
TI  - Constraint-induced aphasia therapy versus intensive semantic treatment in fluent
      aphasia.
AB  - OBJECTIVE: The authors compared the effectiveness of 2 intensive therapy methods:
      Constraint-Induced Aphasia Therapy (CIAT; Pulvermuller et al., 2001) and semantic
      therapy (BOX; Visch-Brink & Bajema, 2001). METHOD: Nine patients with chronic
      fluent aphasia participated in a therapy program to establish behavioral
      treatment outcomes. Participants were randomly assigned to one of two groups
      (CIAT or BOX). RESULTS: Intensive therapy significantly improved verbal
      communication. However, BOX treatment showed a more pronounced improvement on two
      communication-namely, a standardized assessment for verbal communication, the
      Amsterdam Nijmegen Everyday Language Test (Blomert, Koster, & Kean, 1995), and a
      subjective rating scale, the Communicative Effectiveness Index (Lomas et al.,
      1989). All participants significantly improved on one (or more) subtests of the
      Aachen Aphasia Test (Graetz, de Bleser, & Willmes, 1992), an impairment-focused
      assessment. There was a treatment-specific effect. BOX treatment had a
      significant effect on language comprehension and semantics, whereas CIAT
      treatment affected language production and phonology. CONCLUSION: The findings
      indicate that in patients with fluent aphasia, (a) intensive treatment has a
      significant effect on language and verbal communication, (b) intensive therapy
      results in selective treatment effects, and (c) an intensive semantic treatment
      shows a more striking mean improvement on verbal communication in comparison with
      communication-based CIAT treatment.

PMID- 25765603
TI  - Heparin-based nanocapsules as potential drug delivery systems.
AB  - Herein, the synthesis and characterization of heparin-based nanocapsules (NCs) as
      potential drug delivery systems is described. For the synthesis of the heparin
      based NCs, the versatile method of miniemulsion polymerization at the droplets
      interface was achieved resulting in narrowly distributed NCs with 180 nm in
      diameter. Scanning and transmission electron microscopy images showed clearly NC
      morphology. A highly negative charge density for the heparin-based NCs was
      determined by measuring the electro-kinetic potential. Measuring the activated
      clotting time demonstrated the biological intactness of the polymeric shell. The
      ability of heparin-based NCs to bind to antithrombin (AT III) was investigated
      using isothermal titration calorimetry and dynamic light scattering experiments.
      The chemical stability of the NCs was studied in physiological protein-containing
      solutions and also in medically interesting fluids such as sodium chloride 0.9%,
      Ringer's solution, and phosphate buffer saline using dynamic light scattering and
      measuring the fluorescence intensity. The impressive uptake of NCs in different
      cells was confirmed by fluorescence-activated cell sorting, confocal laser
      scanning microscopy, and transmission electron microscopy. The low toxicity of
      all types of NCs was demonstrated.

PMID- 25765604
TI  - Single vial kit formulation of DOTATATE for preparation of (177) Lu-labeled
      therapeutic radiopharmaceutical at hospital radiopharmacy.
AB  - The clinical applications of radiolabeled somatostatin analogue (177) Lu-DOTA
      Tyr(3) -Thr(8) -Octreotide ((177) Lu-DOTATATE) constitute a promising treatment
      option for patients with disseminated and inoperable neuroendocrine (NET) tumors.
      Formulation of (177) Lu-DOTATATE in hospital radiopharmacy under aseptic
      conditions in a safe and reliable manner is a major constraint for its extensive
      use. The present work was intended to develop a kit for the safe preparation of
      the therapeutic radiopharmaceutical, viz. (177) Lu-DOTATATE of high quality that
      can be easily adapted at conventional hospital radiopharmacies. Single vial kits
      of DOTATATE were formulated and evaluated for suitability for radiolabeling as
      well as stability on its storage. Patient dose of (177) Lu-DOTATATE (7.4 GBq)
      could be successfully prepared using semi-automated in-house setup that assures
      safe handling and high yields of product of pharmaceutical purity suitable for
      clinical use. Fast clearance of activity via renal route was observed in
      preclinical biodistribution studies of (177) Lu-DOTATATE carried out in normal
      Swiss mice. Deployment of in-house produced (177) LuCl3 , cold kits and easy
      adaptability of synthesis setup at hospital radiopharmacy for preparation is
      likely to expand applications of peptide receptor radionuclide therapy. 

PMID- 25765606
TI  - Effect of ultrafiltration versus intravenous furosemide for decompensated heart
      failure in cardiorenal syndrome: a systematic review with meta-analysis of
      randomized controlled trials.
AB  - BACKGROUND: Ultrafiltration is an adjunctive treatment for decompensated heart
      failure patients with cardiorenal syndrome. The efficacy and safety of
      ultrafiltration in the patient cohort are still unknown. METHODS: We
      systematically reviewed and evaluated randomized controlled trials, comparing
      diuretics with ultrafiltration in adult patients with decompensated heart failure
      and cardiorenal syndrome through January 2014. The primary outcomes were body
      weight loss and total fluid removal. RESULTS: We identified 8 trials including
      608 patients. In a random-effects model, the pooled difference of body weight
      loss was 1.44 kg between patients receiving ultrafiltration and diuretics (95%
      CI, 0.29-2.59; p = 0.01). The difference of fluid removal was 1.28 l between
      groups (95% CI, 0.43-2.12; p = 0.003). The RR for mortality was 0.90 for
      ultrafiltration compared with diuretics (95% CI, 0.61-1.33; p = 0.60) and the RR
      for renal function deterioration was 1.29 (95% CI, 0.90-1.85; p = 0.17). There is
      a trend toward reducing readmission rate in ultrafiltration group. CONCLUSIONS:
      Ultrafiltration is a safe and effective strategy in the treatment of cardiorenal
      syndrome without increasing the risk of renal deterioration.

PMID- 25765605
TI  - Mechanisms of innate immune evasion in re-emerging RNA viruses.
AB  - Recent outbreaks of Ebola, West Nile, Chikungunya, Middle Eastern Respiratory and
      other emerging/re-emerging RNA viruses continue to highlight the need to further
      understand the virus-host interactions that govern disease severity and infection
      outcome. As part of the early host antiviral defense, the innate immune system
      mediates pathogen recognition and initiation of potent antiviral programs that
      serve to limit virus replication, limit virus spread and activate adaptive immune
      responses. Concordantly, viral pathogens have evolved several strategies to
      counteract pathogen recognition and cell-intrinsic antiviral responses. In this
      review, we highlight the major mechanisms of innate immune evasion by emerging
      and re-emerging RNA viruses, focusing on pathogens that pose significant risk to
      public health. 

PMID- 25765607
TI  - Transcatheter embolization of peripheral renal artery for hemorrhagic urological
      emergencies using FuAiLe medical glue.
AB  - Our objective was to review the technical success and clinical outcomes of
      transcatheter embolization of peripheral renal artery with FuAiLe medical glue
      (FAL). All patients who underwent FAL embolization for peripheral renal artery
      bleeding were retrospectively analyzed for underlying pathologies, technical
      success and outcome of embolization procedure. 14 consecutive patients underwent
      FAL embolization between November 2009 and February 2013. The causes of bleeding
      were post biopsy (n = 5), blunt trauma (n = 5), percutaneous lithotripsy of
      kidney stones (n = 3), and complication of cardiac catheterization (n = 1).
      Bleeding was effectively controlled with a single injection of FAL. Mean volume
      of FAL mixture (FAL:Lipiodol, 1:1) was 0.5 mL (range, 0.2-0.8 mL). No reflux of
      the embolic agent was noted. Average cost of FAL for each procedure was $74.
      Postembolization clinical follow-up showed no evidence of recurrent hematuria,
      progression of hematoma, hypertension, or elevation of serum creatinine. Doppler
      ultrasound examinations in 13 patients demonstrated no abscess, renal parenchyma
      infarction, or renal artery abnormalities. Superselective FAL embolization may be
      used for the treatment of active bleeding from peripheral renal arteries. It has
      a high success rate and is quicker and less expensive than embolization with
      other agents.

PMID- 25765608
TI  - The roles of cortical oscillations in sustained attention.
AB  - We rely on sustained attention to protect task performance against fatigue and
      distraction. Time-related variations in attention correlate with amplitude
      changes of specific cortical oscillations. However, the ways in which these
      oscillations might support sustained attention, how these oscillations are
      controlled, and the extent to which they influence one another remain unclear. We
      address this issue by proposing an oscillatory model of sustained attention.
      Within this framework, sustained attention relies on frontomedial theta
      oscillations, inter-areal communication via low-frequency phase synchronisation,
      and selective excitation and inhibition of cognitive processing through gamma and
      alpha oscillations, respectively. Sustained attention also relies on interactions
      between these oscillations across attention-related brain networks. 

PMID- 25765610
TI  - Waste container weighing data processing to create reliable information of
      household waste generation.
AB  - Household mixed waste container weighing data was processed by knowledge
      discovery and data mining techniques to create reliable information of household
      waste generation. The final data set included 27,865 weight measurements covering
      the whole year 2013 and it was selected from a database of Helsinki Region
      Environmental Services Authority, Finland. The data set contains mixed household
      waste arising in 6m(3) containers and it was processed identifying missing values
      and inconsistently low and high values as errors. The share of missing values and
      errors in the data set was 0.6%. This provides evidence that the waste weighing
      data gives reliable information of mixed waste generation at collection point
      level. Characteristic of mixed household waste arising at the waste collection
      point level is a wide variation between pickups. The seasonal variation pattern
      as a result of collective similarities in behaviour of households was clearly
      detected by smoothed medians of waste weight time series. The evaluation of the
      collection time series against the defined distribution range of pickup weights
      on the waste collection point level shows that 65% of the pickups were from
      collection points with optimally dimensioned container capacity and the
      collection points with over- and under-dimensioned container capacities were
      noted in 9.5% and 3.4% of all pickups, respectively. Occasional extra waste in
      containers occurred in 21.2% of the pickups indicating the irregular behaviour of
      individual households. The results of this analysis show that processing waste
      weighing data using knowledge discovery and data mining techniques provides
      trustworthy information of household waste generation and its variations. 

PMID- 25765609
TI  - Deformation of wrinkled graphene.
AB  - The deformation of monolayer graphene, produced by chemical vapor deposition
      (CVD), on a polyester film substrate has been investigated through the use of
      Raman spectroscopy. It has been found that the microstructure of the CVD graphene
      consists of a hexagonal array of islands of flat monolayer graphene separated by
      wrinkled material. During deformation, it was found that the rate of shift of the
      Raman 2D band wavenumber per unit strain was less than 25% of that of flat flakes
      of mechanically exfoliated graphene, whereas the rate of band broadening per unit
      strain was about 75% of that of the exfoliated material. This unusual deformation
      behavior has been modeled in terms of mechanically isolated graphene islands
      separated by the graphene wrinkles, with the strain distribution in each graphene
      island determined using shear lag analysis. The effect of the size and position
      of the Raman laser beam spot has also been incorporated in the model. The
      predictions fit well with the behavior observed experimentally for the Raman band
      shifts and broadening of the wrinkled CVD graphene. The effect of wrinkles upon
      the efficiency of graphene to reinforce nanocomposites is also discussed. 

PMID- 25765618
TI  - KEEPS, GSM and much more.

PMID- 25765619
TI  - Selection criteria for patients with non-alcoholic fatty liver disease and
      diabetes mellitus to achieve reliable results.

PMID- 25765621
TI  - A critical friend: monitoring and evaluation systems, development cooperation and
      local government. The case of Tuscany.
AB  - The role of monitoring and evaluation (M&E) systems in the field of development
      cooperation has globally increased in last decades. International and regional
      organizations, as well as states, local governments and NGOs have largely adopted
      the tools provided by M&E in order to enhance transparency, effectiveness and
      efficiency. The paper aims at verifying how and to what extent the implementation
      of M&E systems has affected the overall quality of international cooperation
      projects financed by a local government. After a literature review on M&E in
      development cooperation, the research analyzes the wide range of activities
      (evaluation ex-ante, mid-term, final, monitoring, consultancy) carried out by the
      Evaluation Team of the XY in the last eight years in behalf of an Italian local
      government: the Region of Tuscany. The paper reveals the strategic significance
      of adopting M&E systems in the medium-long term. 

PMID- 25765622
TI  - Elucidating the life cycle of Marteilia sydneyi, the aetiological agent of QX
      disease in the Sydney rock oyster (Saccostrea glomerata).
AB  - Marteilia sydneyi (Phylum Paramyxea, Class Marteiliidea, Order Marteiliida) (the
      causative agent of QX disease) is recognised as the most severe parasite to
      infect Saccostrea glomerata, the Sydney rock oyster, on the east coast of
      Australia. Despite its potential impact on industry (>95% mortality), research
      towards lessening these effects has been hindered by the lack of an experimental
      laboratory model of infection as a consequence of our incomplete understanding of
      the life cycle of this parasite. Here, we explored the presence of this parasite
      in hosts other than a bivalve mollusc from two study sites on the Hawkesbury
      River, New South Wales, Australia. We employed PCR-based in situ hybridisation
      and sequence analysis of a portion of the first internal transcribed spacer of
      rDNA in an attempt to detect M. sydneyi DNA in 21 species of polychaete worm.
      Marteilia DNA was detected in 6% of 1247 samples examined by PCR; the analysis of
      all amplicons defined one distinct sequence type for first internal transcribed
      spacer, representing M. sydneyi. Of the polychaete operational taxonomic units
      test-positive in PCR, we examined 116 samples via in situ hybridisation DNA probe
      staining and identified M. sydneyi DNA in the epithelium of the intestine of two
      specimens of Nephtys australiensis. Two differing morphological forms were
      identified: a 'primordial' cell that contained a well-defined nucleus but had
      little differentiation in the cytoplasm, and a 'plasmodial' cell that showed an
      apparent syncytial structure. This finding represents the first known record of
      the identification of M. sydneyi being parasitic in an organism other than an
      oyster, and only the third record of any species of Marteilia identified from non
      molluscan hosts. Future work aims at determining if N. australiensis and S.
      glomerata are the only hosts in the life cycle of this paramyxean, and the
      development of experimental models to aid the production of QX disease-resistant
      oysters.

PMID- 25765623
TI  - Nycteria parasites of Afrotropical insectivorous bats.
AB  - Parasitic protozoan parasites have evolved many co-evolutionary paths towards
      stable transmission to their host population. Plasmodium spp., the causative
      agents of malaria, and related haemosporidian parasites are dipteran-borne
      eukaryotic pathogens that actively invade and use vertebrate erythrocytes for
      gametogenesis and asexual development, often resulting in substantial morbidity
      and mortality of the infected hosts. Here, we present results of a survey of
      insectivorous bats from tropical Africa, including new isolates of species of the
      haemosporidian genus Nycteria. A hallmark of these parasites is their capacity to
      infect bat species of distinct families of the two evolutionary distant
      chiropteran suborders. We did detect Nycteria parasites in both rhinolophid and
      nycterid bat hosts in geographically separate areas of Sub-Saharan Africa,
      however our molecular phylogenetic analyses support the separation of the
      parasites into two distinct clades corresponding to their host genera, suggestive
      of ancient co-divergence and low levels of host switching. For one clade of these
      parasites, cytochrome b genes could not be amplified and cytochrome oxidase I
      sequences showed unusually high rates of evolution, suggesting that the
      mitochondrial genome of these parasites may have either been lost or
      substantially altered. This haemosporidian parasite-mammalian host system also
      highlights that sequential population expansion in the liver and gametocyte
      formation is a successful alternative to intermediate erythrocytic replication
      cycles.

PMID- 25765624
TI  - Formula to evaluate efficacy of vaccines and systemic substances against three
      host ticks.
AB  - The control of ticks with vaccines is of global interest. Experimental vaccines
      incorporate new technologies as soon as they are available. Historically, the
      main vaccine studies have focused on the one-host cattle tick Rhipicephalus
      microplus, and efficacy evaluations have been standardised for this tick species.
      On the other hand, evaluations of vaccine candidates for three-host ticks are
      being done somewhat arbitrarily and thus comparisons within the current
      literature on the efficacy of vaccines, as well as other methods of control, are
      difficult. We herein provide a formula for the evaluation of efficacy of a
      vaccine designed against three-host ticks that incorporates the whole life cycle
      of the tick.

PMID- 25765625
TI  - Rhodium(I)-catalyzed regiospecific dimerization of aromatic acids: two direct C-H
      bond activations in water.
AB  - 2,2'-Diaryl acids are key building blocks for some of the most important and high
      performance polymers such as polyesters and polyamides (imides), as well as
      structural motifs of MOFs (metal-organic frameworks) and biological compounds. In
      this study, a direct, regiospecific and practical dimerization of simple aromatic
      acids to generate 2,2'-diaryl acids has been discovered, which proceeds through
      two rhodium-catalyzed C-H activations in water. This reaction can be easily
      scaled up to gram level by using only 0.4-0.6 mol % of the rhodium catalyst. As a
      proof-of-concept, the natural product ellagic acid was synthesized in two steps
      by this method.

PMID- 25765626
TI  - Hardy-Weinberg equilibrium revisited for inferences on genotypes featuring allele
      and copy-number variations.
AB  - Copy number variations represent a substantial source of genetic variation and
      are associated with a plethora of physiological and pathophysiological
      conditions. Joint copy number and allelic variations (CNAVs) are difficult to
      analyze and require new strategies to unravel the properties of genotype
      distributions. We developed a Bayesian hidden Markov model (HMM) approach that
      allows dissecting intrinsic properties and metastructures of the distribution of
      CNAVs within populations, in particular haplotype phases of genes with varying
      copy numbers. As a key feature, this approach incorporates an extension of the
      Hardy-Weinberg equilibrium, allowing both a comprehensive and parsimonious model
      design. We demonstrate the quality of performance and applicability of the HMM
      approach with a real data set describing the Fcgamma receptor (FcgammaR) gene
      region. Our concept, using a dynamic process to analyze a static distribution,
      establishes the basis for a novel understanding of complex genomic data sets. 

PMID- 25765627
TI  - The clinical effectiveness of transcanalicular diode laser-assisted revision
      surgery for failed endoscopic endonasal dacryocystorhinostomy.
AB  - AIMS: We report the results and clinical effectiveness of transcanalicular diode
      laser-assisted revision surgery for failed endoscopic endonasal
      dacryocystorhinostomy (EDCR). METHODS: We reviewed electronic charts of 53 eyes
      in 51 revision surgery patients, with anatomical failure after primary EDCR.
      RESULTS: The major cause of failed EDCR was membranous obstruction of the
      rhinostomy site (36/53 eyes, 67.9%). The second most common cause of failure was
      granulomatous obstruction (13/53 eyes, 24.5%). The overall success rate of the
      first revision surgery was 83.0% (44/53 eyes). Revision surgery for membranous
      obstruction (36 eyes) showed a 100% success rate, while a 50% success rate was
      achieved in granulomatous obstruction (13 eyes). 2 patients with synechial
      obstruction also showed good results (100%). Sump syndrome (two eyes) showed a
      100% failure rate after revision surgery. When granuloma was the main cause of
      obstruction (13 eyes), the size of the granuloma was correlated with the success
      of revision surgery. Granuloma size was larger in failed revision surgery
      (p=0.002). CONCLUSIONS: A diode laser can achieve effective tissue dissection
      with minimal damage and is a good alternative technique for patients with
      membranous obstruction who had a failed EDCR. However, it may not be appropriate
      for large granulomatous obstruction and sump syndrome.

PMID- 25765628
TI  - KISS1R: Hallmarks of an Effective Regulator of the Neuroendocrine Axis.
AB  - Kisspeptin (KP) is now well recognized as a potent stimulator of gonadotropin
      releasing hormone (GnRH) secretion and thereby a major regulator of the
      neuroendocrine-reproductive axis. KP signals via KISS1R, a G protein-coupled
      receptor (GPCR) that activates the G proteins Galphaq/11. Modulation of the
      interaction of KP with KISS1R is therefore a potential new therapeutic target for
      stimulating (in infertility) or inhibiting (in hormone-dependent diseases) the
      reproductive hormone cascade. Major efforts are underway to target KISS1R in the
      treatment of sex steroid hormone-dependent disorders and to stimulate endogenous
      hormonal responses along the neuroendocrine axis as part of in vitro
      fertilization protocols. The development of analogs modulating KISS1R signaling
      will be aided by an understanding of the intracellular pathways and dynamics of
      KISS1R signaling under normal and pathological conditions. This review focuses on
      KISS1R recruitment of intracellular signaling (Galphaq/11- and beta-arrestin
      dependent) pathways that mediate GnRH secretion and the respective roles of rapid
      desensitization, internalization, and recycling of resensitized receptors in
      maintaining an active population of KISS1R at the cell surface to facilitate
      prolonged KP signaling. Additionally, this review summarizes and discusses the
      major findings of an array of studies examining the desensitization of KP
      signaling in man, domestic and laboratory animals. This discussion highlights the
      major effects of ligand efficacy and concentration and the physiological,
      developmental, and metabolic status of the organism on KP signaling. Finally, the
      potential for the utilization of KP and analogs in stimulating and inhibiting the
      reproductive hormone cascade as an alternative to targeting the downstream GnRH
      receptor is discussed.

PMID- 25765629
TI  - Mesenchymal stem cell exosomes.
AB  - MSCs are an extensively used cell type in clinical trials today. The initial
      rationale for their clinical testing was based on their differentiation
      potential. However, the lack of correlation between functional improvement and
      cell engraftment or differentiation at the site of injury has led to the proposal
      that MSCs exert their effects not through their differentiation potential but
      through their secreted product, more specifically, exosomes, a type of
      extracellular vesicle. We propose here that MSC exosomes function as an extension
      of MSC's biological role as tissue stromal support cells. Like their cell source,
      MSC exosomes help maintain tissue homeostasis for optimal tissue function. They
      target housekeeping biological processes that operate ubiquitously in all tissues
      and are critical in maintaining tissue homeostasis, enabling cells to recover
      critical cellular functions and begin repair and regeneration. This hypothesis
      provides a rationale for the therapeutic efficacy of MSCs and their secreted
      exosomes in a wide spectrum of diseases. Here, we give a brief introduction of
      the biogenesis of MSC exosomes, review their physiological functions and
      highlight some of their biochemical potential to illustrate how MSC exosomes
      could restore tissue homeostasis leading to tissue recovery and repair. 

PMID- 25765630
TI  - Right atrial rupture after road traffic accident.

PMID- 25765631
TI  - Blastic plasmacytoid dendritic cell neoplasm following Waldenstrom
      macroglobulinemia.

PMID- 25765632
TI  - Acute pancreatitis complicated by massive inferior vena cava and right atrial
      thrombosis: a case report.
AB  - Venous thrombosis is a relatively common complication of acute pancreatitis. A 58
      year-old man came to our emergency department with abdominal pain. Pancreatitis
      complicated with a huge thrombosis through inferior vena cava (IVC) to right
      atrium and left renal vein was diagnosed. Gabexate and enoxaparin were
      administered for pancreatitis and thrombosis. Surgical removal of thrombosis was
      considered but was not possible because of poor general condition. Despite
      conservative management, the patient expired. We believe this is the first case
      of pancreatitis complicated by right atrial thrombosis.

PMID- 25765633
TI  - Angioplasty of the common femoral artery and its bifurcation.
AB  - BACKGROUND: To evaluate the efficacy of percutaneous transluminal angioplasty
      (PTA) of atherosclerotic lesions of the common femoral artery (CFA) and its
      bifurcation. METHODS: From 2009 to 2013, 53 patients (43 men, average age, 68
      years) were included in a single-center, nonrandomized, prospective study.
      Indication was disabling intermittent claudication (n = 36) or chronic critical
      limb ischemia (n = 17). Thirty-four procedures (64%) were isolated CFA PTA,
      whereas 7 of 53 (13%) involved inflow (including 4 iliac occlusions) and 12 of 53
      (23%) involved outflow vessels. Primary stenting was performed in 50 cases (95%).
      CFA occlusions were recanalized in 4 of 53. Lesions involved the bifurcation in
      22 cases (40%). Follow-up consisted of clinical examination and duplex scanning
      with ankle-brachial index measurement at 1, 6, and 12 months. A biplane X-ray was
      performed at 1 year. The primary end point was the absence of binary restenosis
      (>50% reobstruction of the CFA). Secondary end points were freedom from target
      lesion revascularization (TLR) and stent fracture rate. RESULTS: Procedural
      success was achieved in 96% of cases. At a mean follow-up of 24 months (with 1
      patient lost of follow-up), the absence of binary restenosis was 92.5%. At the
      end of follow-up, 82% of patients continued to show clinical improvement. Freedom
      from TLR was 97%. Stent fracture rate at 1 year was 9%. CONCLUSIONS: PTA of the
      CFA and its bifurcation is a reliable technique with good midterm functional
      results. These results justify performing a randomized study comparing surgery
      and endovascular treatment.

PMID- 25765634
TI  - Percutaneous pharmacomechanical thrombectomy offers lower risk of post-thrombotic
      syndrome than catheter-directed thrombolysis in patients with acute deep vein
      thrombosis of the lower limb.
AB  - BACKGROUND: Despite optimal anticoagulant therapy, patients with proximal deep
      vein thrombosis (DVT) will often develop post-thrombotic syndrome (PTS). Early
      thromboreduction can potentially decrease the risk of PTS by restoring venous
      patency and preserving valvular function. This study was undertaken to compare
      the efficacy and treatment outcomes of patients with acute proximal DVT of the
      lower limb who underwent either catheter-directed thrombolysis (CDT) or
      percutaneous pharmacomechanical thrombectomy (PMT). METHODS: Thirty-nine patients
      with acute proximal DVT of the lower limb who were diagnosed by Wells' Score, PMT
      or CDT was chosen depending on the patient. They underwent early
      thromboreduction, and 3 died postoperatively in less than 12 months, while 2 were
      removed for not following-up. Thirty-four patients, 16 in PMT and 18 in CDT, were
      followed up for more than 1 year. Venous Registry Index (VRI) was used to
      evaluate the postprocedural patency, while PTS was assessed using the Villalta
      scale. RESULTS: The technical success was 100% in both the groups, without any 30
      day mortality. VRI changed from 13.1 +/- 4.3 preoperatively to 2.4 +/- 1.5
      postoperatively in the PMT group, and from 11.8 +/- 2.4 to 3.6 +/- 2.2 in the CDT
      group. Thrombolysis rate was 81.5 +/- 8.5% and 67.7 +/- 21.0% in the PMT and CDT
      groups, respectively (P = 0.059). There were no differences in complications,
      thrombus score, and VRI between the 2 groups. Primary patency rate at 1 year was
      93.8% in the PMT group and 88.9% in the CDT group (P = 0.648). The Villalta scale
      was 2.1 +/- 3.0 in the PMT group and 5.1 +/- 4.1 in the CDT group (P = 0.030).
      CONCLUSIONS: Both PMT and CDT are effective treatment modalities in patients with
      acute proximal DVT. Compared with CDT, PMT provides similar treatment success,
      but with lower risk of PTS at 1-year follow-up.

PMID- 25765635
TI  - Open retrograde endovascular stenting for left common carotid artery dissection
      secondary to surgical repair of acute aortic dissection: a case report and review
      of the literature.
AB  - A 30-year-old male presented with an acute aortic artery dissection (Stanford
      type A) and underwent total arch replacement using a stented elephant trunk
      technique. One month later, the patient developed dissections in the innominate
      and left common carotid artery (CCA). The innominate artery dissection caused
      occlusion in the right internal carotid artery (ICA) and a major stroke.
      Dissection of the left CCA progressed and extended to the bifurcation site.
      Antegrade access for a left carotid intervention was deemed as difficult because
      of the previously implanted stent and the additional risks of embolic events and
      dissection enlargement. Hybrid procedures combining left carotid bifurcation
      exposure and retrograde endovascular stenting were successfully completed. This
      report is a rare case of retrograde endovascular reconstruction for the left CCA
      dissection following surgical repair of an aortic artery dissection. Here, we
      also review previous cases of iatrogenic carotid dissections following surgical
      intervention. 

PMID- 25765636
TI  - Surgical treatment of localized dissection of the internal carotid artery.
AB  - Dissection of the internal carotid artery is very rare; however, it is diagnosed
      more frequently with increasing radiographic diagnostic tools. Patients may be
      completely asymptomatic or may present with symptoms ranging between localized
      pain to severe cerebral ischemic events. Treatment is usually medical or with
      interventional radiographic tools. In this report, we present surgical management
      of internal carotid artery dissection in a 61-year-old female patient.

PMID- 25765637
TI  - Thirty-day outcome of delayed versus early management of symptomatic carotid
      stenosis.
AB  - BACKGROUND: The aim of this study was to compare outcomes of early (<15 days)
      versus delayed carotid endarterectomy (CEA) in symptomatic patients. METHODS: All
      CEA procedures performed for symptomatic carotid stenosis between January 2006
      and May 2010 were retrospectively reviewed. Postoperative mortality (within 30
      days), stroke, and myocardial infarction (MI) rates were analyzed in the early
      and delayed CEA groups. RESULTS: During the study period, 149 patients were
      included. Carotid revascularization was performed within 15 days after symptom
      onset in 62 (41.6%) patients and longer than 15 days after symptom onset in 87
      (58.4%) patients. The mean time lapse between onset of neurological symptoms and
      surgery was 9.3 days (range 1-15) in the early surgery group and 47.9 days (range
      16-157) in the delayed surgery group. Thirty-day combined stroke and death rates
      were, respectively, 1.7% and 3.5% in the early and the delayed surgery groups.
      Thirty-day combined stroke, death, and MI rates were, respectively, 1.7% and 5.9%
      in the early and the delayed surgery groups. CONCLUSION: During the study period,
      the reduction of the symptom-to-knife time in application to the carotid
      revascularization guidelines did not impact our outcomes suggesting that early
      CEA achieves 30-day mortality and morbidity rates at least equivalent to those of
      delayed CEA.

PMID- 25765638
TI  - Descending thoracic aorta remodeling after multilayer stent release.
AB  - The multilayer flow modulator (MFM) is a device whose real effectiveness in the
      treatment of thoracoabdominal aortic aneurysms is not clear yet. A 68-year-old
      man with a 18-mm blister-like aneurysm of the descending thoracic aorta underwent
      endovascular exclusion, complicated by the thrombosis of a previous aortobi-iliac
      prosthesis, treated with embolectomy and femorofemoral bypass. Therefore, an MFM
      placement was planned. The postoperative course was uneventful and the 6-month
      computed tomography scan showed a complete thrombosis and remodeling of the
      aneurysm. The MFM stent could be an alternative treatment for saccular thoracic
      aortic aneurysm in high-risk patients but should not be used indiscriminately
      when other modalities of aortic repair are not feasible. Longer follow-up is
      mandatory to prove the efficacy of this technology.

PMID- 25765639
TI  - Type IIIb endoleak after thoracic endovascular aortic repair caused by endoanchor
      dislocation.
AB  - BACKGROUND: The aim of this study was to report the occurrence of a type IIIb
      endoleak after endovascular repair of a thoracic aortic aneurysm caused by
      endoanchor dislocation. CASE REPORT: An 84-year-old female patient underwent
      thoracic endovascular repair for aneurysmal disease of her thoracic aorta. The
      procedure included primary left subclavian artery revascularization and the
      placement of endoanchors to enhance fixation of the endograft within the aortic
      arch. Dislocation of one of the endoanchors resulted in a graft defect leading to
      a type IIIb endoleak and aortic diameter expansion. CONCLUSIONS: Endoanchors
      represent a promising adjunct in endovascular repair settings. However, their use
      requires careful procedure planning and special attention during follow-up.

PMID- 25765640
TI  - Genome engineering of isogenic human ES cells to model autism disorders.
AB  - Isogenic pluripotent stem cells are critical tools for studying human
      neurological diseases by allowing one to study the effects of a mutation in a
      fixed genetic background. Of particular interest are the spectrum of autism
      disorders, some of which are monogenic such as Timothy syndrome (TS); others are
      multigenic such as the microdeletion and microduplication syndromes of the
      16p11.2 chromosomal locus. Here, we report engineered human embryonic stem cell
      (hESC) lines for modeling these two disorders using locus-specific endonucleases
      to increase the efficiency of homology-directed repair (HDR). We developed a
      system to: (1) computationally identify unique transcription activator-like
      effector nuclease (TALEN) binding sites in the genome using a new software
      program, TALENSeek, (2) assemble the TALEN genes by combining golden gate cloning
      with modified constructs from the FLASH protocol, and (3) test the TALEN pairs in
      an amplification-based HDR assay that is more sensitive than the typical non
      homologous end joining assay. We applied these methods to identify, construct,
      and test TALENs that were used with HDR donors in hESCs to generate an isogenic
      TS cell line in a scarless manner and to model the 16p11.2 copy number disorder
      without modifying genomic loci with high sequence similarity. 

PMID- 25765641
TI  - Accurate read-based metagenome characterization using a hierarchical suite of
      unique signatures.
AB  - A major challenge in the field of shotgun metagenomics is the accurate
      identification of organisms present within a microbial community, based on
      classification of short sequence reads. Though existing microbial community
      profiling methods have attempted to rapidly classify the millions of reads output
      from modern sequencers, the combination of incomplete databases, similarity among
      otherwise divergent genomes, errors and biases in sequencing technologies, and
      the large volumes of sequencing data required for metagenome sequencing has led
      to unacceptably high false discovery rates (FDR). Here, we present the
      application of a novel, gene-independent and signature-based metagenomic
      taxonomic profiling method with significantly and consistently smaller FDR than
      any other available method. Our algorithm circumvents false positives using a
      series of non-redundant signature databases and examines Genomic Origins Through
      Taxonomic CHAllenge (GOTTCHA). GOTTCHA was tested and validated on 20 synthetic
      and mock datasets ranging in community composition and complexity, was applied
      successfully to data generated from spiked environmental and clinical samples,
      and robustly demonstrates superior performance compared with other available
      tools. 

PMID- 25765642
TI  - Broadening the versatility of lentiviral vectors as a tool in nucleic acid
      research via genetic code expansion.
AB  - With the aim of broadening the versatility of lentiviral vectors as a tool in
      nucleic acid research, we expanded the genetic code in the propagation of
      lentiviral vectors for site-specific incorporation of chemical moieties with
      unique properties. Through systematic exploration of the structure-function
      relationship of lentiviral VSVg envelope by site-specific mutagenesis and
      incorporation of residues displaying azide- and diazirine-moieties, the
      modifiable sites on the vector surface were identified, with most at the PH
      domain that neither affects the expression of envelope protein nor propagation or
      infectivity of the progeny virus. Furthermore, via the incorporation of such
      chemical moieties, a variety of fluorescence probes, ligands, PEG and other
      functional molecules are conjugated, orthogonally and stoichiometrically, to the
      lentiviral vector. Using this methodology, a facile platform is established that
      is useful for tracking virus movement, targeting gene delivery and detecting
      virus-host interactions. This study may provide a new direction for rational
      design of lentiviral vectors, with significant impact on both basic research and
      therapeutic applications. 

PMID- 25765643
TI  - Unwinding forward and sliding back: an intermittent unwinding mode of the BLM
      helicase.
AB  - There are lines of evidence that the Bloom syndrome helicase, BLM, catalyzes
      regression of stalled replication forks and disrupts displacement loops (D-loops)
      formed during homologous recombination (HR). Here we constructed a forked DNA
      with a 3' single-stranded gap and a 5' double-stranded handle to partly mimic a
      stalled DNA fork and used magnetic tweezers to study BLM-catalyzed unwinding of
      the forked DNA. We have directly observed that the BLM helicase may slide on the
      opposite strand for some distance after duplex unwinding at different forces. For
      DNA construct with a long hairpin, progressive unwinding of the hairpin is
      frequently interrupted by strand switching and backward sliding of the enzyme.
      Quantitative study of the uninterrupted unwinding length (time) has revealed a
      two-state-transition mechanism for strand-switching during the unwinding process.
      Mutational studies revealed that the RQC domain plays an important role in
      stabilizing the helicase/DNA interaction during both DNA unwinding and backward
      sliding of BLM. Especially, Lys1125 in the RQC domain, a highly conserved amino
      acid among RecQ helicases, may be involved in the backward sliding activity. We
      have also directly observed the in vitro pathway that BLM disrupts the mimic
      stalled replication fork. These results may shed new light on the mechanisms for
      BLM in DNA repair and homologous recombination. 

PMID- 25765644
TI  - Silent mutations at codons 65 and 66 in reverse transcriptase alleviate indel
      formation and restore fitness in subtype B HIV-1 containing D67N and K70R drug
      resistance mutations.
AB  - Resistance to combined antiretroviral therapy (cART) in HIV-1-infected
      individuals is typically due to nonsynonymous mutations that change the protein
      sequence; however, the selection of synonymous or 'silent' mutations in the HIV-1
      genome with cART has been reported. These silent K65K and K66K mutations in the
      HIV-1 reverse transcriptase (RT) occur in over 35% of drug-experienced
      individuals and are highly associated with the thymidine analog mutations D67N
      and K70R, which confer decreased susceptibility to most nucleoside and nucleotide
      RT inhibitors. However, the basis for selection of these silent mutations under
      selective drug pressure is unknown. Using Illumina next-generation sequencing, we
      demonstrate that the D67N/K70R substitutions in HIV-1 RT increase indel frequency
      by 100-fold at RT codons 65-67, consequently impairing viral fitness.
      Introduction of either K65K or K66K into HIV-1 containing D67N/K70R reversed the
      error-prone DNA synthesis at codons 65-67 in RT and improved viral replication
      fitness, but did not impact RT inhibitor drug susceptibility. These data provide
      new mechanistic insights into the role of silent mutations selected during
      antiretroviral therapy and have broader implications for the relevance of silent
      mutations in the evolution and fitness of RNA viruses.

PMID- 25765645
TI  - Probing a label-free local bend in DNA by single molecule tethered particle
      motion.
AB  - Being capable of characterizing DNA local bending is essential to understand
      thoroughly many biological processes because they involve a local bending of the
      double helix axis, either intrinsic to the sequence or induced by the binding of
      proteins. Developing a method to measure DNA bend angles that does not perturb
      the conformation of the DNA itself or the DNA-protein complex is a challenging
      task. Here, we propose a joint theory-experiment high-throughput approach to
      rigorously measure such bend angles using the Tethered Particle Motion (TPM)
      technique. By carefully modeling the TPM geometry, we propose a simple formula
      based on a kinked Worm-Like Chain model to extract the bend angle from TPM
      measurements. Using constructs made of 575 base-pair DNAs with in-phase
      assemblies of one to seven 6A-tracts, we find that the sequence CA6CGG induces a
      bend angle of 19 degrees  +/- 4 degrees . Our method is successfully compared to
      more theoretically complex or experimentally invasive ones such as cyclization,
      NMR, FRET or AFM. We further apply our procedure to TPM measurements from the
      literature and demonstrate that the angles of bends induced by proteins, such as
      Integration Host Factor (IHF) can be reliably evaluated as well. 

PMID- 25765646
TI  - A statistical framework for revealing signaling pathways perturbed by DNA
      variants.
AB  - Much of the inter-individual variation in gene expression is triggered via
      perturbations of signaling networks by DNA variants. We present a novel
      probabilistic approach for identifying the particular pathways by which DNA
      variants perturb the signaling network. Our procedure, called PINE, relies on a
      systematic integration of established biological knowledge of signaling networks
      with data on transcriptional responses to various experimental conditions. Unlike
      previous approaches, PINE provides statistical aspects that are critical for
      prioritizing hypotheses for followup experiments. Using simulated data, we show
      that higher accuracy is attained with PINE than with existing methods. We used
      PINE to analyze transcriptional responses of immune dendritic cells to several
      pathogenic stimulations. PINE identified statistically significant genetic
      perturbations in the pathogen-sensing signaling network, suggesting previously
      uncharacterized regulatory mechanisms for functional DNA variants. 

PMID- 25765647
TI  - The structure of human SFPQ reveals a coiled-coil mediated polymer essential for
      functional aggregation in gene regulation.
AB  - SFPQ, (a.k.a. PSF), is a human tumor suppressor protein that regulates many
      important functions in the cell nucleus including coordination of long non-coding
      RNA molecules into nuclear bodies. Here we describe the first crystal structures
      of Splicing Factor Proline and Glutamine Rich (SFPQ), revealing structural
      similarity to the related PSPC1/NONO heterodimer and a strikingly extended
      structure (over 265 A long) formed by an unusual anti-parallel coiled-coil that
      results in an infinite linear polymer of SFPQ dimers within the crystals. Small
      angle X-ray scattering and transmission electron microscopy experiments show that
      polymerization is reversible in solution and can be templated by DNA. We
      demonstrate that the ability to polymerize is essential for the cellular
      functions of SFPQ: disruptive mutation of the coiled-coil interaction motif
      results in SFPQ mislocalization, reduced formation of nuclear bodies, abrogated
      molecular interactions and deficient transcriptional regulation. The coiled-coil
      interaction motif thus provides a molecular explanation for the functional
      aggregation of SFPQ that directs its role in regulating many aspects of cellular
      nucleic acid metabolism. 

PMID- 25765648
TI  - Single molecule TPM analysis of the catalytic pentad mutants of Cre and Flp site
      specific recombinases: contributions of the pentad residues to the pre-chemical
      steps of recombination.
AB  - Cre and Flp site-specific recombinase variants harboring point mutations at their
      conserved catalytic pentad positions were characterized using single molecule
      tethered particle motion (TPM) analysis. The findings reveal contributions of
      these amino acids to the pre-chemical steps of recombination. They suggest
      functional differences between positionally conserved residues in how they
      influence recombinase-target site association and formation of 'non-productive',
      'pre-synaptic' and 'synaptic' complexes. The most striking difference between the
      two systems is noted for the single conserved lysine. The pentad residues in Cre
      enhance commitment to recombination by kinetically favoring the formation of pre
      synaptic complexes. These residues in Flp serve a similar function by promoting
      Flp binding to target sites, reducing non-productive binding and/or enhancing the
      rate of assembly of synaptic complexes. Kinetic comparisons between Cre and Flp,
      and between their derivatives lacking the tyrosine nucleophile, are consistent
      with a stronger commitment to recombination in the Flp system. The effect of
      target site orientation (head-to-head or head-to-tail) on the TPM behavior of
      synapsed DNA molecules supports the selection of anti-parallel target site
      alignment prior to the chemical steps. The integrity of the synapse, whose
      establishment/stability is fostered by strand cleavage in the case of Flp but not
      Cre, appears to be compromised by the pentad mutations.

PMID- 25765649
TI  - A diverse epigenetic landscape at human exons with implication for expression.
AB  - DNA methylation is an important epigenetic marker associated with gene expression
      regulation in eukaryotes. While promoter methylation is relatively well
      characterized, the role of intragenic DNA methylation remains unclear. Here, we
      investigated the relationship of DNA methylation at exons and flanking introns
      with gene expression and histone modifications generated from a human fibroblast
      cell-line and primary B cells. Consistent with previous work we found that
      intragenic methylation is positively correlated with gene expression and that
      exons are more highly methylated than their neighboring intronic environment.
      Intriguingly, in this study we identified a unique subset of hypomethylated exons
      that demonstrate significantly lower methylation levels than their surrounding
      introns. Furthermore, we observed a negative correlation between exon methylation
      and the density of the majority of histone modifications. Specifically, we
      demonstrate that hypo-methylated exons at highly expressed genes are associated
      with open chromatin and have a characteristic histone code comprised of
      significantly high levels of histone markings. Overall, our comprehensive
      analysis of the human exome supports the presence of regulatory hypomethylated
      exons in protein coding genes. In particular our results reveal a previously
      unrecognized diverse and complex role of the epigenetic landscape within the gene
      body. 

PMID- 25765650
TI  - The hub protein loquacious connects the microRNA and short interfering RNA
      pathways in mosquitoes.
AB  - Aedes aegypti mosquitoes vector several arboviruses of global health
      significance, including dengue viruses and chikungunya virus. RNA interference
      (RNAi) plays an important role in antiviral immunity, gene regulation and
      protection from transposable elements. Double-stranded RNA binding proteins
      (dsRBPs) are important for efficient RNAi; in Drosophila functional
      specialization of the miRNA, endo-siRNA and exo-siRNA pathway is aided by the
      dsRBPs Loquacious (Loqs-PB, Loqs-PD) and R2D2, respectively. However, this
      functional specialization has not been investigated in other dipterans. We were
      unable to detect Loqs-PD in Ae. aegypti; analysis of other dipteran genomes
      demonstrated that this isoform is not conserved outside of Drosophila.
      Overexpression experiments and small RNA sequencing following depletion of each
      dsRBP revealed that R2D2 and Loqs-PA cooperate non-redundantly in siRNA
      production, and that these proteins exhibit an inhibitory effect on miRNA levels.
      Conversely, Loqs-PB alone interacted with mosquito dicer-1 and was essential for
      full miRNA production. Mosquito Loqs interacted with both argonaute 1 and 2 in a
      manner independent of its interactions with dicer. We conclude that the
      functional specialization of Loqs-PD in Drosophila is a recently derived trait,
      and that in other dipterans, including the medically important mosquitoes, Loqs
      PA participates in both the miRNA and endo-siRNA based pathways. 

PMID- 25765651
TI  - Analysis of strand-specific RNA-seq data using machine learning reveals the
      structures of transcription units in Clostridium thermocellum.
AB  - Identification of transcription units (TUs) encoded in a bacterial genome is
      essential to elucidation of transcriptional regulation of the organism. To gain a
      detailed understanding of the dynamically composed TU structures, we have used
      four strand-specific RNA-seq (ssRNA-seq) datasets collected under two
      experimental conditions to derive the genomic TU organization of Clostridium
      thermocellum using a machine-learning approach. Our method accurately predicted
      the genomic boundaries of individual TUs based on two sets of parameters
      measuring the RNA-seq expression patterns across the genome: expression-level
      continuity and variance. A total of 2590 distinct TUs are predicted based on the
      four RNA-seq datasets. Among the predicted TUs, 44% have multiple genes. We
      assessed our prediction method on an independent set of RNA-seq data with longer
      reads. The evaluation confirmed the high quality of the predicted TUs. Functional
      enrichment analyses on a selected subset of the predicted TUs revealed
      interesting biology. To demonstrate the generality of the prediction method, we
      have also applied the method to RNA-seq data collected on Escherichia coli and
      achieved high prediction accuracies. The TU prediction program named SeqTU is
      publicly available at https://code.google.com/p/seqtu/. We expect that the
      predicted TUs can serve as the baseline information for studying transcriptional
      and post-transcriptional regulation in C. thermocellum and other bacteria. 

PMID- 25765652
TI  - Evolutionary patterns of DNA base composition and correlation to polymorphisms in
      DNA repair systems.
AB  - DNA base composition is a fundamental genome feature. However, the evolutionary
      pattern of base composition and its potential causes have not been well
      understood. Here, we report findings from comparative analysis of base
      composition at the whole-genome level across 2210 species, the polymorphic-site
      level across eight population comparison sets, and the mutation-site level in 12
      mutation-tracking experiments. We first demonstrate that base composition follows
      the individual-strand base equality rule at the genome, chromosome and
      polymorphic-site levels. More intriguingly, clear separation of base-composition
      values calculated across polymorphic sites was consistently observed between
      basal and derived groups, suggesting common underlying mechanisms. Individuals in
      the derived groups show an A&T-increase/G&C-decrease pattern compared with the
      basal groups. Spontaneous and induced mutation experiments indicated these
      patterns of base composition change can emerge across mutation sites. With base
      composition across polymorphic sites as a genome phenotype, genome scans with
      human 1000 Genomes and HapMap3 data identified a set of significant genomic
      regions enriched with Gene Ontology terms for DNA repair. For three DNA repair
      genes (BRIP1, PMS2P3 and TTDN), ENCODE data provided evidence for interaction
      between genomic regions containing these genes and regions containing the
      significant SNPs. Our findings provide insights into the mechanisms of genome
      evolution. 

PMID- 25765653
TI  - Trade-offs between tRNA abundance and mRNA secondary structure support smoothing
      of translation elongation rate.
AB  - Translation of protein from mRNA is a complex multi-step process that occurs at a
      non-uniform rate. Variability in ribosome speed along an mRNA enables refinement
      of the proteome and plays a critical role in protein biogenesis. Detailed single
      protein studies have found both tRNA abundance and mRNA secondary structure as
      key modulators of translation elongation rate, but recent genome-wide ribosome
      profiling experiments have not observed significant influence of either on
      translation efficiency. Here we provide evidence that this results from an
      inherent trade-off between these factors. We find codons pairing to high
      abundance tRNAs are preferentially used in regions of high secondary structure
      content, while codons read by significantly less abundant tRNAs are located in
      lowly structured regions. By considering long stretches of high and low mRNA
      secondary structure in Saccharomyces cerevisiae and Escherichia coli and
      comparing them to randomized-gene models and experimental expression data, we
      were able to distinguish clear selective pressures and increased protein
      expression for specific codon choices. The trade-off between secondary structure
      and tRNA-concentration based codon choice allows for compensation of their
      independent effects on translation, helping to smooth overall translational speed
      and reducing the chance of potentially detrimental points of excessively slow or
      fast ribosome movement.

PMID- 25765655
TI  - H3K9 methyltransferase G9a negatively regulates UHRF1 transcription during
      leukemia cell differentiation.
AB  - Histone H3K9 methyltransferase (HMTase) G9a-mediated transcriptional repression
      is a major epigenetic silencing mechanism. UHRF1 (ubiquitin-like with PHD and
      ring finger domains 1) binds to hemimethylated DNA and plays an essential role in
      the maintenance of DNA methylation. Here, we provide evidence that UHRF1 is
      transcriptionally downregulated by H3K9 HMTase G9a. We found that increased
      expression of G9a along with transcription factor YY1 specifically represses
      UHRF1 transcription during TPA-mediated leukemia cell differentiation. Using ChIP
      analysis, we found that UHRF1 was among the transcriptionally silenced genes
      during leukemia cell differentiation. Using a DNA methylation profiling array, we
      discovered that the UHRF1 promoter was hypomethylated in samples from leukemia
      patients, further supporting its overexpression and oncogenic activity. Finally,
      we showed that G9a regulates UHRF1-mediated H3K23 ubiquitination and proper DNA
      replication maintenance. Therefore, we propose that H3K9 HMTase G9a is a specific
      epigenetic regulator of UHRF1. 

PMID- 25765654
TI  - RAD54 family translocases counter genotoxic effects of RAD51 in human tumor
      cells.
AB  - The RAD54 family DNA translocases have several biochemical activities. One
      activity, demonstrated previously for the budding yeast translocases, is ATPase
      dependent disruption of RAD51-dsDNA binding. This activity is thought to promote
      dissociation of RAD51 from heteroduplex DNA following strand exchange during
      homologous recombination. In addition, previous experiments in budding yeast have
      shown that the same activity of Rad54 removes Rad51 from undamaged sites on
      chromosomes; mutants lacking Rad54 accumulate nonrepair-associated complexes that
      can block growth and lead to chromosome loss. Here, we show that human RAD54 also
      promotes the dissociation of RAD51 from dsDNA and not ssDNA. We also show that
      translocase depletion in tumor cell lines leads to the accumulation of RAD51 on
      chromosomes, forming complexes that are not associated with markers of DNA
      damage. We further show that combined depletion of RAD54L and RAD54B and/or
      artificial induction of RAD51 overexpression blocks replication and promotes
      chromosome segregation defects. These results support a model in which RAD54L and
      RAD54B counteract genome-destabilizing effects of direct binding of RAD51 to
      dsDNA in human tumor cells. Thus, in addition to having genome-stabilizing DNA
      repair activity, human RAD51 has genome-destabilizing activity when expressed at
      high levels, as is the case in many human tumors.

PMID- 25765657
TI  - A fluorescence-based helicase assay: application to the screening of G-quadruplex
      ligands.
AB  - Helicases, enzymes that unwind DNA or RNA structure, are present in the cell
      nucleus and in the mitochondrion. Although the majority of the helicases unwind
      DNA or RNA duplexes, some of these proteins are known to resolve unusual
      structures such as G-quadruplexes (G4) in vitro. G4 may form stable barrier to
      the progression of molecular motors tracking on DNA. Monitoring G4 unwinding by
      these enzymes may reveal the mechanisms of the enzymes and provides information
      about the stability of these structures. In the experiments presented herein, we
      developed a reliable, inexpensive and rapid fluorescence-based technique to
      monitor the activity of G4 helicases in real time in a 96-well plate format. This
      system was used to screen a series of G4 structures and G4 binders for their
      effect on the Pif1 enzyme, a 5' to 3' DNA helicase. This simple assay should be
      adaptable to analysis of other helicases and G4 structures. 

PMID- 25765656
TI  - Srs2 promotes Mus81-Mms4-mediated resolution of recombination intermediates.
AB  - A variety of DNA lesions, secondary DNA structures or topological stress within
      the DNA template may lead to stalling of the replication fork. Recovery of such
      forks is essential for the maintenance of genomic stability. The structure
      specific endonuclease Mus81-Mms4 has been implicated in processing DNA
      intermediates that arise from collapsed forks and homologous recombination.
      According to previous genetic studies, the Srs2 helicase may play a role in the
      repair of double-strand breaks and ssDNA gaps together with Mus81-Mms4. In this
      study, we show that the Srs2 and Mus81-Mms4 proteins physically interact in vitro
      and in vivo and we map the interaction domains within the Srs2 and Mus81
      proteins. Further, we show that Srs2 plays a dual role in the stimulation of the
      Mus81-Mms4 nuclease activity on a variety of DNA substrates. First, Srs2 directly
      stimulates Mus81-Mms4 nuclease activity independent of its helicase activity.
      Second, Srs2 removes Rad51 from DNA to allow access of Mus81-Mms4 to cleave DNA.
      Concomitantly, Mus81-Mms4 inhibits the helicase activity of Srs2. Taken together,
      our data point to a coordinated role of Mus81-Mms4 and Srs2 in processing of
      recombination as well as replication intermediates. 

PMID- 25765658
TI  - Relationship between physical occupational exposures and health on semen quality:
      data from the Longitudinal Investigation of Fertility and the Environment (LIFE)
      Study.
AB  - OBJECTIVE: To study the relationship among occupation, health, and semen quality
      in a cohort of men attempting to conceive. DESIGN: Observational prospective
      cohort. SETTING: Not applicable. PATIENT(S): A total of 501 couples discontinuing
      contraception were followed for 1 year while trying to conceive; 473 men (94%)
      provided one semen sample, and 80% provided a second sample. INTERVENTION(S):
      None. MAIN OUTCOME MEASURE(S): Semen data obtained through at-home semen
      collection with next-day analysis/quantification. RESULT(S): In all, complete
      data were available for 456 men, with a mean age of 31.8 years. Work-related
      heavy exertion was consistently associated with lower semen concentration and
      total sperm count. Thirteen percent of men who reported heavy exertion displayed
      oligospermia, compared with 6% who did not report workplace exertion. Shift work,
      night work, vibration, noise, heat, and prolonged sitting were not associated
      with semen quality. Men with high blood pressure had significantly lower strict
      morphology scores compared with normotensive men (17% vs. 21%). In contrast,
      hyperlipidemia, diabetes, and composite of total comorbidities were not
      associated with semen quality. The number of medications a man was taking as a
      proxy of health status was associated with semen quality. There was a negative
      association between number of medications and sperm count. CONCLUSION(S): A
      negative relationship among occupational exertion, hypertension, and the number
      of medications with semen quality was identified. As these are potentially
      modifiable factors, further research should determine whether treatment or
      cessation may improve male fecundity.

PMID- 25765659
TI  - Acute arteriovenous access failure: long-term outcomes of endovascular salvage
      and assessment of co-variates affecting patency.
AB  - AIMS: This study reports long-term outcomes after endovascular salvage (EVS) for
      acute dialysis fistula/graft dysfunction. METHODS: All patients presenting with
      acute fistula or graft dysfunction, excluding primary failures, referred for
      endovascular salvage were included in this single-centre prospective study.
      RESULTS: Altogether, 410 procedures were carried out in 232 patients. Overall,
      the incidence of thrombosis/occlusion (per patient-year) was 0.12 for fistulae
      and 0.9 for grafts. The anatomical success rate for EVS was 94% for fistulae and
      92% for grafts. Primary patency rates for fistulae at 1, 6, 12, 24 and 36 months
      were 82, 64, 44, 34 and 26%, respectively, whereas secondary patency rates were
      88, 84, 74, 69 and 61%, respectively. Primary patency rates for grafts at 1, 6
      and 12 months were 50, 14 and 8%. The overall rate of complications was 6% with
      no incidence of symptomatic pulmonary embolism. In a Cox regression model, upper
      arm location of fistula (HR 1.9, p = 0.04, n = 144) was associated with lower
      primary patency, whereas the presence of thrombosis was associated lower primary
      (HR 1.9, p = 0.004, n = 144) and secondary patency (HR 3.7, p < 0.001, n = 144).
      Aspirin therapy was associated with longer primary patency (HR 0.6, p = 0.02, n =
      144) and secondary patency (HR 0.58, p = 0.08, n = 144). CONCLUSION: EVS is
      effective but longer-term outcomes are poor. Presence of thrombosis portends poor
      fistula survival and strategies for prevention need attention. Balloon
      maceration, our preferred declotting technique, is safe and the most cost
      effective method. Aspirin therapy for patients presenting with failure of
      fistulae deserves further investigation.

PMID- 25765661
TI  - Tweak regulates astrogliosis, microgliosis and skeletal muscle atrophy in a mouse
      model of amyotrophic lateral sclerosis.
AB  - Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder that
      primarily affects motoneurons in the brain and spinal cord. Astrocyte and
      microglia activation as well as skeletal muscle atrophy are also typical
      hallmarks of the disease. However, the functional relationship between
      astrocytes, microglia and skeletal muscle in the pathogenic process remains
      unclear. Here, we report that the tumor necrosis factor-like weak inducer of
      apoptosis (Tweak) and its receptor Fn14 are aberrantly expressed in spinal
      astrocytes and skeletal muscle of SOD1(G93A) mice. We show that Tweak induces
      motoneuron death, stimulates astrocytic interleukin-6 release and astrocytic
      proliferation in vitro. The genetic ablation of Tweak in SOD1(G93A) mice
      significantly reduces astrocytosis, microgliosis and ameliorates skeletal muscle
      atrophy. The peripheral neutralization of Tweak through antagonistic anti-Tweak
      antibody ameliorates muscle pathology and notably, decreases microglial
      activation in SOD1(G93A) mice. Unexpectedly, none of these approaches improved
      motor function, lifespan and motoneuron survival. Our work emphasizes the multi
      systemic aspect of ALS, and suggests that a combinatorial therapy targeting
      multiple cell types will be instrumental to halt the neurodegenerative process. 

PMID- 25765662
TI  - A 3'-UTR mutation creates a microRNA target site in the GFPT1 gene of patients
      with congenital myasthenic syndrome.
AB  - Mutations in the gene encoding glutamine-fructose-6-phosphate transaminase 1
      (GFPT1) cause the neuromuscular disorder limb-girdle congenital myasthenic
      syndrome (LG-CMS). One recurrent GFPT1 mutation detected in LG-CMS patients is a
      c.*22C>A transversion in the 3'-untranslated region (UTR). Because this variant
      does not alter the GFPT1 open reading frame, its pathogenic relevance has not yet
      been established. We found that GFPT1 protein levels were reduced in myoblast
      cells of the patients carrying this variant. In silico algorithms predicted that
      the mutation creates a microRNA target site for miR-206*. Investigation of the
      expression of this so far unrecognized microRNA confirmed that miR-206* (like its
      counterpart miR-206) is abundant in skeletal muscle. MiR-206* efficiently reduced
      the expression of reporter constructs containing the mutated 3'-UTR while no such
      effect was observed with reporter constructs containing the wild-type 3'-UTR or
      when a specific anti-miR-206* inhibitor was added. Moreover, anti-miR-206*
      inhibitor treatment substantially rescued GFPT1 expression levels in patient
      derived myoblasts. Our data demonstrate that the c.*22C>A mutation in the GFPT1
      gene leads to illegitimate binding of microRNA resulting in reduced protein
      expression. We confirm that c.*22C>A is a causative mutation and suggest that
      formation of microRNA target sites might be a relevant pathomechanism in
      Mendelian disorders. Variants in the 3'-UTRs should be considered in genetic
      diagnostic procedures. 

PMID- 25765663
TI  - Biocompatibility reduces inflammation-induced apoptosis in mesothelial cells
      exposed to peritoneal dialysis fluid.
AB  - BACKGROUND/AIMS: Peritonitis is a major complication that arises out of
      peritoneal dialysis (PD), leading to death and loss of mesothelium and peritoneal
      injury, which may impede PD. We studied the combined impact of inflammatory
      mediators and PD fluids on mesothelial cell death. METHODS: Cultured human
      mesothelial cells. RESULTS: Inflammatory cytokines (TNF-alpha and interferon
      gamma) cooperate with bioincompatible PD fluids containing high glucose
      degradation product (GDP) concentrations to promote mesothelial cell death. Thus,
      the inflammatory cytokine cocktail induced a higher rate of death in cells
      cultured in high GDP PD fluid than in low GDP PD fluid or cell culture medium
      (cell death expressed as % hypodiploid cells: TNF-alpha and interferon-gamma in
      RPMI: 14.15 +/- 1.68, TNF-alpha and interferon-gamma in 4.25% low GDP PD fluid
      13.16 +/- 3.29, TNF-alpha and interferon-gamma in 4.25% high GDP PD fluid 25.88
      +/- 2.18%, p < 0.05 vs. the other two groups). BclxL BH4 peptides, Apaf-1
      inhibition or caspase inhibition failed to protect from apoptosis induced by the
      combination of inflammatory cytokines and bioincompatible PD fluids, although
      they protected from other forms of mesothelial cell apoptosis. CONCLUSION:
      Inflammation cooperates with high GDP PD fluids to promote mesothelial cell
      death, which is resistant to several therapeutic approaches. This information
      provides a framework for selection of PD fluid during peritonitis.

PMID- 25765664
TI  - A family with permanent neonatal diabetes due to a novel mutation in INS gene.
AB  - In this report we present a family with permanent neonatal diabetes, heterozygous
      for a novel INS gene missense mutation, p.A24V, manifested with marked
      hyperglycemia and ketoacidosis, unstable glycemic control, requiring insulin
      therapy, rapid progression of long-term complications and accompanying physical
      pathological signs and brain lesions. 

PMID- 25765665
TI  - A classification model for predicting eye disease in newly diagnosed people with
      type 2 diabetes.
AB  - Diabetic retinopathy may be present at the time type 2 diabetes is diagnosed, and
      initial screening encompassing an eye examination performed by an ophthalmologist
      or optometrist is therefore recommended. However, proper screening for
      retinopathy may be challenging in many parts of the world. We hypothesized that
      simple, commonly available patient characteristics can be used to identify
      patients at high risk for having retinopathy. We investigated data from multiple
      years extracted from the National Health and Nutrition Examination Survey which
      holds information about blood glucose and eye examinations. Individuals with
      hitherto undiagnosed diabetes were classified according to the presence or
      absence of retinopathy. Linear classification was used to predict which patients
      had retinopathy at the time of diagnosis. A total of 266 individuals with
      undiagnosed diabetes were identified from the cohorts. Of these, 222 individuals
      had no sign of retinopathy, whereas 44 had mild or moderate non-proliferative
      retinopathy. Using information regarding HbA1c, BMI, waist circumference, age,
      systolic blood pressure, urinary albumin, and urinary creatinine, we were able to
      construct a model that predicts the presence of retinopathy with a positive
      predictive value of 22% and a negative predictive value of 99%. Only one true
      positive (1/44) with mild non-proliferative retinopathy was falsely classified. A
      classification model using readily available patient information and routine
      biochemical measures can be used to identify patients at high risk of having
      retinopathy at the time their diabetes is diagnosed. The model may be used to
      identify high-risk patients for retinopathy screening. 

PMID- 25765666
TI  - Curcumin attenuates cardiomyocyte hypertrophy induced by high glucose and insulin
      via the PPARgamma/Akt/NO signaling pathway.
AB  - AIM: To investigate the potential effect of curcumin on cardiomyocyte hypertrophy
      and a possible mechanism involving the PPARgamma/Akt/NO signaling pathway in
      diabetes. METHODS: The cardiomyocyte hypertrophy induced by high glucose
      (25.5mmol/L) and insulin (0.1MUmol/L) (HGI) and the antihypertrophic effect of
      curcumin were evaluated in primary culture by measuring the cell surface area,
      protein content and atrial natriuretic factor (ANF) mRNA expression. The mRNA and
      protein expressions were assayed by reverse transcription PCR and Western
      blotting, whereas the NO concentration and endothelial NO synthase (eNOS)
      activity were determined using nitrate reduction and ELISA methods, respectively.
      RESULTS: The cardiomyocyte hypertrophy induced by HGI was characterized by
      increasing ANF mRNA expression, total protein content, and cell surface area,
      with downregulated mRNA and protein expressions of both PPARgamma and Akt, which
      paralleled the declining eNOS mRNA expression, eNOS content, and NO
      concentration. The effects of HGI were inhibited by curcumin (1, 3, 10MUmol/L) in
      a concentration-dependent manner. GW9662 (10MUmol/L), a selective PPARgamma
      antagonist, could abolish the effects of curcumin. LY294002 (20MUmol/L), an Akt
      blocker, and N(G)-nitro-l-arginine-methyl ester (100MUmol/L), a NOS inhibitor,
      could also diminish the effects of curcumin. CONCLUSIONS: The results suggested
      that curcumin supplementation can improve HGI-induced cardiomyocytes hypertrophy
      in vitro through the activation of PPARgamma/Akt/NO signaling pathway.

PMID- 25765667
TI  - Temporal trends in initial and recurrent lower extremity amputations in people
      with and without diabetes in Western Australia from 2000 to 2010.
AB  - AIMS: To examine temporal trends in lower extremity amputations in people with
      type 1 diabetes, type 2 diabetes and cardiovascular disease (CVD) without
      diabetes in Western Australia (WA) from 2000 to 2010. METHODS: We used linked
      health data to identify all non-traumatic lower extremity amputations in adults
      aged >=20 years with diabetes and/or CVD from 2000 to 2010 in WA. Annual age- and
      sex-standardised rates of total, initial and recurrent amputations, stratified by
      major and minor status, were calculated for type 1 and type 2 diabetes, and CVD
      without diabetes, from the at-risk population for each group. Age- and sex
      adjusted trends were estimated from Poisson regression models. RESULTS: 5891
      lower extremity amputations were identified. Peripheral vascular disease (71%),
      hypertension (70%) and chronic kidney disease (60%) were highly prevalent.
      Average annual rates of total amputations were 724, 564 and 66 per 100,000 person
      years in type 1, type 2 diabetes and CVD without diabetes respectively. Rates of
      initial amputations fell significantly by 2.4%/year (95% CI -3.5, -1.4) in type 2
      diabetes, with similar declines for type 1 diabetes and CVD without diabetes
      (interaction p=0.96), driven by large falls in major amputations. There was
      limited improvement in recurrence rates overall, with recurrent minor amputations
      increasing significantly in type 2 diabetes (+3.5%/year, 95% CI +1.3%, +5.7%).
      CONCLUSION: Lower extremity amputation rates have declined at a population level
      in people with diabetes and CVD without diabetes, suggesting improvements in
      prevention and management for this high-risk patient group, however limited
      declines in recurrent amputations requires further investigation.

PMID- 25765668
TI  - Impact of the International Association of Diabetes and Pregnancy Study Groups
      criteria for gestational diabetes.
AB  - AIMS: To evaluate the diagnostic criteria of the International Association of
      Diabetes and Pregnancy Study Groups (IADPSG) and alternative criteria in terms of
      resultant prevalence of gestational diabetes mellitus (GDM) and measures of
      diagnostic impact. METHODS: The Brazilian Gestational Diabetes Study (EBDG) is a
      cohort of pregnant women enrolled consecutively in prenatal care clinics of the
      Brazilian National Health Service from 1991 to 1995, a time and setting in which
      those with lesser than diabetes hyperglycemia rarely received drug treatment.
      Eligibility criteria were age >=20 years, gestational age 20-28 weeks and no
      history of diabetes outside pregnancy. After interview and anthropometric
      measurements, a standardized 2h 75g OGTT was scheduled. Women were followed
      through early postpartum. RESULTS: Prevalence of GDM defined by IADPSG criteria
      was 18.0% (95% CI 16.9-19.0), ranging from 2.7 to 17.0% with the alternative
      criteria. Relative risks for large for gestational age (LGA) and preeclampsia
      were generally small. The diagnostic impact assessed by pre- to post-test gain in
      the probability of an outcome was also small (3.6% for LGA and 0.5% for
      preeclampsia). Alternative criteria reached maximum gains of 9.7% and 5.3%,
      respectively. The fractions of LGA births and preeclampsia attributable to GDM by
      the IADPSG criteria were small, 6.7% and 3.5%, respectively. CONCLUSIONS: The
      IADPSG criteria identify more women as having GDM but their diagnostic and
      population impacts with respect to adverse outcomes are small. Alternative
      definitions, although also presenting small diagnostic and population impacts,
      showed advantages which may be useful in specific settings.

PMID- 25765669
TI  - Risk factors for the development of glucocorticoid-induced diabetes mellitus.
AB  - AIMS: To evaluate the incidence of glucocorticoid-induced diabetes mellitus (GC
      DM) by repeated measurements of the postprandial glucose and detect predictors
      for the development of GC-DM. METHODS: Inpatients with rheumatic or renal disease
      who received glucocorticoid therapy were enrolled in this study. We compared the
      clinical and laboratory parameters of the GC-DM group with the non-GC-DM group
      and performed a multivariate analysis to identify risk factors. RESULTS: During a
      four-week period, 84 of the 128 patients (65.6%) developed GC-DM. All patients
      were diagnosed based on the detection of postprandial hyperglycemia. The GC-DM
      group had an older age (65.2 vs. 50.4 years, p<0.0001), higher levels of fasting
      plasma glucose (93.3 vs. 89.0mg/dl, p=0.027) and HbA1c (5.78 vs. 5.50%, 39.7 vs.
      36.6 mmol/mol, p=0.001) and lower eGFR values (54.0 vs. 77.1 ml/min/1.73 m(2),
      p=0.0003) than the non-GC-DM group. According to the multivariate analysis, an
      older age (more than or equal to 65 years), higher HbA1c level (more than or
      equal to 6.0%) and lower eGFR (<40 ml/min/1.73m(2)) were identified as
      independent risk factors for GC-DM (OR 2.95, 95% CI 1.15-7.92, OR: 3.05, 95% CI
      1.11-9.21, OR: 3.42, 95% CI: 1.22-10.8, respectively). The risk ratio for the
      development of GC-DM in the patients with at least one of these three risk
      factors was 2.28. The dose of glucocorticoids was not statistically related to
      the development of GC-DM. CONCLUSIONS: Patients with an older age, higher HbA1c
      level and lower eGFR require close monitoring for the development of GC-DM,
      regardless of the dose of glucocorticoids being administered.

PMID- 25765670
TI  - Insulin requirement profiles of short-term intensive insulin therapy in patients
      with newly diagnosed type 2 diabetes and its association with long-term glycemic
      remission.
AB  - AIMS: To investigate the insulin requirement profiles during short-term intensive
      continuous subcutaneous insulin infusion (CSII) in patients with newly diagnosed
      type 2 diabetes and its relationship with long-term glycemic remission. METHODS:
      CSII was applied in 104 patients with newly diagnosed type 2 diabetes. Daily
      insulin doses were titrated and recorded to achieve and maintain euglycemia for 2
      weeks. Measurements of blood glucose, lipid profiles as well as intravenous
      glucose tolerance tests were performed before and after the therapy. Afterwards,
      patients were followed up for 1 year. RESULTS: Total daily insulin dose (TDD) was
      56.6+/-16.1IU at the first day when euglycemia was achieved (TDD-1). Thereafter,
      TDD progressively decreased at a rate of 1.4+/-1.0IU/day to 36.2+/-16.5IU at the
      end of the therapy. TDD-1 could be estimated with body weight, FPG, triglyceride
      and waist circumference in a multiple linear regression model. Decrement of TDD
      after euglycemia was achieved (DeltaTDD) was associated with reduction of HOMA-IR
      (r=0.27, P=0.008) but not with improvement in beta cell function. Patients in the
      lower tertile of DeltaTDD had a significantly higher risk of hyperglycemia
      relapse than those in the upper tertile within 1 year (HR 3.4, 95%CI [1.4, 8.4],
      P=0.008). CONCLUSIONS: There is a steady decline of TDD after euglycemia is
      achieved in patients with newly diagnosed type 2 diabetes treated with CSII, and
      DeltaTDD is associated with a better long-term glycemic outcome.

PMID- 25765672
TI  - Biocomputing - tools, aims, perspectives.
AB  - Biomolecular systems for information processing have recently received great
      attention in the general framework of unconventional computing. While DNA
      biocomputing systems have been studied by many researchers and have already
      reached a high level of complexity, enzyme-based cascades mimicking Boolean logic
      operations are a relatively new subfield that is rapidly progressing. The present
      paper reviews recent progress in the enzyme-based information processing systems
      and suggests applications in biosensing, rather than computation. Specific
      examples of enzyme-based logic systems are discussed to introduce readers to this
      rapidly developing research area. 

PMID- 25765671
TI  - Sustained effects of a protein 'preload' on glycaemia and gastric emptying over 4
      weeks in patients with type 2 diabetes: A randomized clinical trial.
AB  - We have shown that the capacity of 25g whey preloads to slow gastric emptying and
      reduce postprandial glycaemia persists after 4 weeks regular exposure in patients
      with diet-controlled type 2 diabetes. This dietary strategy therefore appears
      feasible for larger clinical trials to evaluate beneficial effects on long-term
      glycaemic control. Registered with the Australian New Zealand Clinical Trials
      Registry: ACTRN12614000831684. 

PMID- 25765673
TI  - Immediate story recall in elderly individuals with memory complaints: how much
      does it contribute to memory assessment?
AB  - BACKGROUND: Prose memory tests exhibit ecological validity, but the influence of
      non-memory functions on immediate recall in elderly subjects with memory
      complaints has not been fully investigated. This study examined (1) whether the
      ability to immediately recall a story can distinguish among clinical controls,
      amnesic mild cognitive impairment (MCI) and dementia due to Alzheimer's disease
      (AD) and (2) which cognitive functions contribute to immediate recall
      performance. METHODS: A total of 73 consecutive volunteers (50 women and 23 men)
      aged 47-88 (mean age = 71.85 +/- 9.41) and with a mean schooling level of 12.51
      (SD = 4.09) participated in the experiment. All individuals were seeking
      specialized evaluation because of memory complaints. Diagnoses were made by
      considering clinical, neuropsychological, and MRI assessments collected by a
      multidisciplinary team of neurologists, neuropsychologists, and speech-language
      therapists. A total of 26 individuals were classified as clinical controls; 27 as
      MCI patients; and 20 as having AD dementia. All individuals in the AD group had a
      Clinical Dementia Rating (CDR) <= 1. RESULTS: Immediate recall was only able to
      distinguish AD subjects from MCI patients and clinical controls (p > 0.05).
      Stepwise multiple linear regression analysis revealed that mental status (MMSE),
      semantic memory (WAIS-III vocabulary) and episodic memory (RAVLT primacy)
      explained approximately 62% of the variance in immediate recall. CONCLUSIONS:
      Understanding the value and limitations of immediate story recall in
      distinguishing between MCI and AD may help clinicians in better choosing
      cognitive tests to diagnose MCI.

PMID- 25765674
TI  - An experimental and theoretical magneto-structural study of polynuclear Ni(II)
      complexes assembled from a versatile bis(salicylaldehyde)diamine polytopic
      ligand.
AB  - Six novel Ni(II) complexes, ranging from mononuclear to tetranuclear, have been
      prepared from the polytopic symmetrical Mannich base ligand N,N'-dimethyl-N,N'
      bis(2-hidroxy-3-formyl-5-bromo-benzyl)ethylenediamine (H2L) and different anionic
      coligands: [Ni(H2L)(NO3)(H2O)]NO3.H2O (), [Ni2(MU-L)(acac)2(H2O)].CH3CN (),
      [Ni2(MU-L)(MU-OAc)(NCS)] (), [Ni3(MU-L)2(MU-OH2)2(H2O)(CH3CN)](NO3)2.4CH3CN (),
      [Ni4(MU-L)2(MU-OAc)2(MU-OCH3)2].6H2O.2CH3OH () and [Ni4(MU-L)2(MU-OAc)2(MU
      N3)2].2H2O.CH3OH (). These complexes have been characterized by single crystal X
      ray diffraction, magnetic measurements and DFT theoretical calculations. The
      structural analysis of these complexes reveals that the anionic coligand and
      reaction conditions play a fundamental role in determining their final structures
      and magnetic properties. Compound contains a monomeric cationic unit with the
      nickel ion coordinated in the external O4 site of the compartmental ligand H2L,
      which acts in a neutral zwitterionic form. Complexes and are dinuclear Ni2
      neutral entities, in which the Ni(II) ions are connected through two MU-phenoxido
      bridging groups. The Ni(O)2Ni bridging fragment in is almost planar, whereas in
      is bent due to the additional presence of a syn-syn acetate bridge connecting the
      Ni(II) atoms. Complex has a bent trinuclear structure with double MU-phenoxido/MU
      water bridges between the central and terminal nickel atoms. Complexes and are
      Ni4 complexes with defective dicubane structures, in which triple MU
      phenoxido/MU1,1,1-X/syn-syn acetate and double MU-phenoxido/MU1,1,1-X mixed
      bridges connect central and terminal Ni(II) atoms, whereas double MU1,1,1-X
      bridging ligands link the central Ni(II) ions (X = methoxido and azido groups for
      and , respectively). Magnetic susceptibility measurements reveal that complex
      shows a moderate antiferromagnetic interaction between the Ni(II) ions through
      the double di-MU-phenoxido bridge, leading to a S = 0 ground state. Compared to ,
      complex shows a much weaker magnetic exchange interaction due the counter
      complementarity effect provoked by the additional presence of the syn-syn acetate
      bridging group, as well as the non-planarity of the bridging fragment. In complex
      , the double MU-phenoxido/MU-water mixed bridges lead to very weak
      antiferromagnetic interactions between the central and external Ni(II) ions.
      Overall ferromagnetic interactions are found for , and , although in not all the
      magnetic pathways transmit ferromagnetic interactions. A detailed analysis of the
      magnetic exchange interactions transmitted through the different pathways as well
      as DFT calculations on the X-ray structures of compounds were performed to
      support the magneto-structural data of these compounds. 

PMID- 25765675
TI  - Role of the intestinal cytokine microenvironment in shaping the intraepithelial
      lymphocyte repertoire.
AB  - Local resident IELs are composed of distinct subsets of T cells with potent
      cytolytic and immunoregulatory capacities. As IELs are located within this unique
      interface between the core of the body and the outside environment, the specific
      development and function of intestinal IELs must be tightly regulated. To
      accomplish this, the cytokine microenvironment of the intestine has evolved
      sophisticated mechanisms that modulate the phenotype, ontogeny, and function of
      these cells. In this review, we summarize the evidence demonstrating the origin
      of certain intestinal cytokines, including IL-7, IL-15, IL-2, TGF-beta, and SCF
      and discuss what influence such cytokines may have on IELs. Moreover, we review
      data suggesting that the abnormal expression of cytokines that leads to the
      heightened activation of IELs may also contribute to immunopathological responses
      or exacerbate inflammatory diseases, such as IBD and celiac disease, or promote
      cancer development and progression.

PMID- 25765676
TI  - Human blood CD1c dendritic cells stimulate IL-12-independent IFN-gamma responses
      and have a strikingly low inflammatory profile.
AB  - Adaptive immune responses are initiated by resident myeloid tissue DC. A major
      fraction of tissue DC express CD1c+ and is thought to be derived from blood CD1c
      DC, an idea supported here by the observation that they express tissue-homing
      molecules and rapidly differentiate into cells with a tissue DC phenotype.
      Responses are thought to be augmented/modulated further by inflammatory moDC.
      Although much accepted human myeloid DC cell biology is based on moDC studies, we
      find these 2 DC populations to be functionally distinct. Stimulated moDC produce
      high levels of IL-10 and the Th1-promoting cytokine IL-12. Under identical
      conditions, CD1c DC synthesized no IL-10 and no or low levels of IL-12. Despite
      this, CD1c DC stimulated a strong Th1 response, demonstrated by IL-12
      neutralization to be IL-12 independent, whereas the response induced by moDC was
      IL-12 dependent. This finding was supported by studies on a patient with a highly
      reduced ability to synthesize IL-12, whose CD1c DC induced a good Th1 response
      contrasting with the failure of his moDC, which were impaired in IL-12
      production, to induce IFN-gamma-secreting T cells. The IL-10 and IL-12 data were
      confirmed by microarray analysis, which also showed that stimulated moDC produced
      inflammatory-associated chemokines and cytokines, whereas stimulated CD1c DC
      showed minimal up-regulation of these genes. Thus, moDC, widely used as a human
      myeloid DC model, do not faithfully reflect the properties of CD1c tissue DC,
      making the initial response to a pathogen or vaccine.

PMID- 25765677
TI  - ADAM9 disintegrin domain activates human neutrophils through an autocrine circuit
      involving integrins and CXCR2.
AB  - ADAM9 is a member of the ADAM family whose expression positively correlates with
      tumor progression. Besides the metalloprotease activity, ADAM9D interacts with
      different integrins, modulating cell-adhesion events. Previous studies pointed to
      an important role for neutrophils in tumor development, as the inhibition of
      neutrophil migration or depletion of this immune cell impairs tumor growth.
      However, our understanding of the molecular mechanisms involved in this process,
      as well as the main key players acting on neutrophils, is very limited. Here, we
      investigated the possible modulatory effects of ADAM9D on human neutrophil
      functions. Our results show that ADAM9D promotes neutrophil activation and
      chemotaxis in a process that depends on the engagement of alphavbeta3 and
      alpha9beta1 integrins and on the activation of PI3K/Akt and MAPK signaling
      pathway. ADAM9D impairs migration of neutrophils toward fMLP, LTB4, and IL-8 as
      classic chemoattractants. This effect is blocked by PTX, a G(i)PCR inhibitor.
      Furthermore, CXCR2 antagonists RPTX and SB225002 also impaired neutrophil
      chemotaxis in response to ADAM9D, suggesting a hierarchical cross-talk of
      integrins with CXCR2. Our results indicate that ADAM9D activates neutrophil
      functions and may be implicated in the inflammatory events associated with cancer
      and other disorders.

PMID- 25765678
TI  - n-3 Polyunsaturated fatty acids and mast cell activation.
AB  - Mast cells are known to play a vital role in the development of inflammation in
      allergic responses. Recent studies have indicated that mast cell activation could
      be modulated by n-3 PUFAs, which have a wide range of well-documented health
      benefits. In our review, we summarize the recent findings and potential
      mechanisms of the effect of n-3 PUFAs on mast cell activation. This knowledge
      could provide new strategies for the development of therapeutic interventions for
      diseases mediated by mast cells.

PMID- 25765679
TI  - Allergen induced pulmonary inflammation enhances mammary tumor growth and
      metastasis: Role of CHI3L1.
AB  - Metastasis is the primary cause of mortality in women with breast cancer.
      Metastasis to the lungs is greater in patients with pulmonary inflammatory
      illnesses. It is unknown how pre-existing pulmonary inflammation affects mammary
      tumor progression. We developed a novel breast cancer model in which pulmonary
      inflammation is induced in mice prior to tumor cell implantation. In the present
      study, we determined how pre-existing allergen-induced inflammation changes the
      pulmonary microenvironment to exacerbate tumor metastasis. We showed that pre
      existing pulmonary inflammation in mammary tumor bearers is associated with: 1)
      an increase in growth of the primary tumor and metastasis; 2) an increase in the
      expression of a glycoprotein known as CHI3L1; and 3) increase in the levels of
      myeloid populations in their lungs. We also showed that myeloid derived cells
      from the lungs of allergic tumor bearers produce higher amounts of CHI3L1 than
      the saline controls. We previously showed that CHI3L1 induces the expression of
      proinflammatory and protumorigenic molecules. In this study, we show that CHI3L1
      knockout tumor bearers with pre-existing allergic pulmonary inflammation had
      decreased levels of myeloid-derived cells, decreased levels of proinflammatory
      mediators, and a significant reduction in tumor volume and metastasis compared
      with the wild-type controls. Pre-existing inflammation and CHI3L1 might be
      driving the establishment of a premetastatic milieu in the lungs and aiding in
      the support of metastatic foci. Understanding the role of allergen-induced CHI3L1
      and inflammation in tumor bearers and its effects on the pulmonary
      microenvironment could result in targeted therapies for breast cancer.

PMID- 25765680
TI  - Trogocytic CD137 transfer causes an internalization of CD137 ligand on murine
      APCs leading to reduced T cell costimulation.
AB  - CD137 ligand (CD137L) is expressed on APCs and crosslinks CD137, a powerful
      costimulatory molecule on T cells during cognate interactions, and thereby
      greatly enhances immune responses. We report that CD137 can be transferred from
      activated T cells and from tumor cells that express CD137 to other cells via
      trogocytosis. This trogocytic transfer is independent of CD137L expression by the
      recipient cell. However, if CD137L is present on the recipient cell, the
      transferred CD137 binds to CD137L and the CD137-CD137L complex becomes
      internalized. The removal of CD137L from the surface of APCs lowers their ability
      to costimulate T cells, as evidenced by a reduced IFN-gamma secretion. Removal of
      CD137L on APCs by trogocytic transfer of CD137 occurs within 1 h and requires
      cell-cell contact and the continuous presence of CD137-expressing cells.
      Bidirectional signaling exists for the CD137 receptor/ligand system, because
      CD137L also signals into APCs. We propose that the trogocytic transfer of CD137
      from activated T cells to APCs and the subsequent removal of CD137L from APCs is
      a physiologic regulatory mechanism that limits immune activity. Furthermore, we
      hypothesize that the trogocytic transfer of CD137 occurs in cancers and quenches
      the activity of APCs, contributing to the cancer cells escaping immune
      surveillance. Taken together, our findings demonstrate that the trogocytic
      transfer of CD137 leads to an internalization of CD137L on APCs and a reduction
      in immune activity.

PMID- 25765681
TI  - Neutrophil-derived MRP-14 is up-regulated in infectious osteomyelitis and
      stimulates osteoclast generation.
AB  - Bone infections of patients with joint replacement by endoprosthesis (so called
      "periprosthetic joint infection") pose a severe problem in the field of
      orthopedic surgery. The diagnosis is often difficult, and treatment is, in most
      cases, complicated and prolonged. Patients often require an implant exchange
      surgery, as the persistent infection and the accompanying inflammation lead to
      tissue damage with bone degradation and consequently, to a loosening of the
      implant. To gain insight into the local inflammatory process, expression of the
      proinflammatory cytokine MRP-14, a major content of neutrophils, and its link to
      subsequent bone degradation was evaluated. We found MRP-14 prominently expressed
      in the affected tissue of patients with implant-associated infection, in close
      association with the chemokine CXCL8 and a dense infiltrate of neutrophils and
      macrophages. In addition, the number of MRP-14-positive cells correlated with the
      presence of bone-resorbing osteoclasts. MRP-14 plasma concentrations were
      significantly higher in patients with implant-associated infection compared with
      patients with sterile inflammation or healthy individuals, advocating MRP-14 as a
      novel diagnostic marker. A further biologic activity of MRP-14 was detected: rMRP
      14 directly induced the differentiation of monocytes to osteoclasts, thus linking
      the inflammatory response in implant infections with osteoclast generation, bone
      degradation, and implant loosening. 

PMID- 25765682
TI  - Follicle-stimulating hormone receptor (FSHR) in Chinese alligator, Alligator
      sinensis: molecular characterization, tissue distribution and mRNA expression
      changes during the female reproductive cycle.
AB  - The follicle-stimulating hormone (FSH) plays a central role in vertebrate
      reproduction, with the actions of FSH mediated by FSH receptors (FSHRs) on the
      granulosa cells of the ovary. The present study reports the cloning and
      characterization of FSHR in Chinese alligator, Alligator sinensis (caFSHR), and
      its tissue distribution and mRNA expression changes during the reproductive
      cycle. The mature protein of caFSHR displays typical features of the glycoprotein
      hormone receptor family, but also contains some remarkable differences when
      compared with other vertebrate FSHRs. The deduced amino acid sequence of the
      caFSHR shares identity of 85% with Chinese softshell turtle, 84-87% with birds,
      77-78% with mammals, 67-73% with amphibians and 51-58% with fishes. Phylogenetic
      tree analysis of the FSHR amino acid sequence indicated that alligators cluster
      into the bird branch. Tissue expression analysis showed that caFSHR was not only
      expressed in the ovary, but also in the stomach, intestine, pancreas liver and
      oviduct at similar levels, while it was not detectable in heart, thymus or
      thyroid. Expression of caFSHR in the ovary is high in May (breeding prophase) and
      peaks in July during the breeding period, where it is maintained at high levels
      through September (breeding anaphase). Expression decreases significantly in
      November (hibernating period) and then remains relatively low from January to
      March (hibernating period). These temporal changes in FSHR expression suggest
      that it plays an important role in promoting ovarian development during the
      female reproductive cycle of Chinese alligator. 

PMID- 25765683
TI  - [Mucocutaneous diseases and murine models with death of keratinocytes induced by
      lichenoid tissue reaction/interface dermatitis].
AB  - A set of histopathological elements with death of epidermal basal cell layer
      keratinocytes along with inflammatory cell infiltration distinguishes lichenoid
      tissue reaction (LTR)/interface dermatitis (IFD) from other inflammatory
      mucocutaneous diseases. The LTR/IFD can be seen in skin disorders like as lichen
      planus, acute graft-versus-host disease, lupus erythematosus, dermatomyositis,
      and toxic epidermal necrolysis/Stevesn-Johnson syndrome. Clinical and basic
      researches suggested that cytotoxic CD8 T cells producing interferon-gamma and
      FasL are final effector cells to cause apoptosis of keratinocyte. Some murine
      models of LTR/IFD have been established, for example, LTR/IFD reactions of
      keratinocyte-specific ovalbumin (OVA)-transgenic mice after OVA-specific T-cell
      receptor(+)CD8 T cells. By analysis of the murine model, a new class of
      immunosuppressant, a JAK inhibitor, has been suggested as a new candidate for
      treatment of LTR/IFD.

PMID- 25765684
TI  - [IgG4-related kidney disease. Diagnosis and treatment].
AB  - IgG4-related disease (IgG4-RD) is a systemic inflammatory disorder that can
      affect most organs/tissues like sarcoidosis. The kidney is one of the most
      frequently affected organs. While tubulointerstitial nephritis (TIN) with
      characteristic imaging findings is the representative lesion of IgG4-related
      kidney disease (IgG4-RKD), a variety of glomerular lesions, particularly
      membranous nephropathy, sometimes overlap on TIN. Clinically, either decreased
      renal function and/or characteristic imaging findings such as multiple low
      density lesions on contrast-enhanced computed tomography are typical presenting
      features. Histologically, plasma cell (PC)-rich TIN accompanied by characteristic
      fibrosis called storiform fibrosis with dense IgG4-positive PC infiltration is a
      typical finding. Although a swift response to corticosteroid is a very important
      feature of IgG4-RKD, in cases with moderately to severely decreased renal
      function before therapy, only partial recovery of renal function is obtained.
      This review provides a comprehensive overview of IgG4-RKD from the clinical,
      laboratory, imaging, and histological aspects and also addresses some of the
      therapeutic issues concerning it.

PMID- 25765685
TI  - [Osteoclast biology and osteoimmunology].
AB  - The bony skeleton enables the locomotive activity, the storage of calcium, and
      the harboring of the hematopoietic stem cells from which blood and immune cells
      are derived. The immune and skeletal systems share various molecules including
      cytokines, signaling molecules, transcription factors and membrane receptors.
      Investigation into rheumatoid arthritis (RA) as well as cloning of RANKL and
      various bone phenotypes found in immune-compromised gene deficient mice has
      highlighted the importance of the dynamic interplay between the both systems.
      These findings have recently led to both the emergence and subsequent rapid
      evolution of the field of osteoimmunology. The scope of osteoimmunology has been
      extended to encompass a wide range of molecular and cellular interactions, the
      elucidation of which will provide a scientific basis for future therapeutic
      approaches to diseases related to the immune and skeletal systems.

PMID- 25765686
TI  - [The role of podocyte injury in chronic kidney disease].
AB  - It has recently become clear that initial glomerular injury affects glomerular
      visceral epithelial cells (also called as podocytes) as important target cells
      for progression of chronic kidney disease (CKD) and end-stage kidney disease.
      Podocytes are injured in many human kidney diseases including minimal change
      disease, focal segmental glomerulosclerosis, diabetic nephropathy, membranous
      nephropathy and lupus nephritis. Podocytes are highly specialized epithelial
      cells that cover the outer layer of the glomerular basement membrane (GBM).
      Podocytes serve as the final barrier to urinary protein loss through the special
      formation and maintenance of foot-processes and an interposed slit-diaphragm.
      Chronic podocyte injury may cause podocyte detachment from the GBM, which leads
      to glomerulosclerosis. The elucidation of podocyte biology during the last 15
      years has significantly improved our understanding of the pathophysiologic
      processes of proteinuria and glomerulosclerosis. In this review, we highlight
      some of new data including our recent findings for translating podocyte biology
      into new examinations and therapies for podocyte injury.

PMID- 25765687
TI  - [Niacin deficiency and cutaneous immunity].
AB  - Niacin, also known as vitamin B3, is required for the synthesis of coenzymes,
      nicotinamide adenine dinucleotide (NAD) and nicotinamide adenine dinucleotide
      phosphate (NADP). Niacin binds with G protein-coupled receptor (GPR) 109A on
      cutaneous Langerhans cells and causes vasodilation with flushing in head and neck
      area. Niacin deficiency due to excessive alcohol consumption, certain drugs or
      inadequate uptake in diet causes pellagra, a photosensitivity dermatitis.
      Recently several studies have revealed the mechanism of photosensitivity in
      niacin deficiency, which may pave a way for new therapeutic approaches. The
      expression level of prostaglandin E synthase (PTGES) is up-regulated in the skin
      of both pellagra patients and niacin deficient pellagra mouse models. In
      addition, pellagra is mediated through prostaglandin E2-EP4 (PGE2-EP4) signaling
      via reactive oxygen species (ROS) production in keratinocytes. In this article,
      we have reviewed the role of niacin in immunity and the mechanism of niacin
      deficiency-induced photosensitivity.

PMID- 25765688
TI  - [Management of rheumatoid arthritis medications and pregnancy].
AB  - Rheumatoid arthritis (RA) affects mainly women during their childbearing years.
      As aging of childbirth advances in Japan, women who plan pregnancy would increase
      after they developed RA. Recent findings showed that high disease activity of RA
      might impair fertility. Planning pregnancy is preferable after female patients
      achive and maintain low disease activity or remission of RA. Women on
      methotrexate, which is the anchor drug for RA, need to discontinue the medication
      with a high risk of causing birth defects during conception and pregnancy. Data
      of RA patients exposed TNF inhibitors during pregnancy has been accumulating in
      recent years. These data suggest that increased risk of spontaneous abortion and
      congenital abnomalies has not been observed. Although there is insufficient data
      about safety of breastfeeding while using TNF inhibitors, the secretion of the
      drugs in breast milk is very little and fetal toxicity has not been observed.
      Since long term safety of children exposed TNF inhibitors in uterus has not been
      established, we should discontinue the drugs as soon as pregnancy is recognized.
      TNF inhibitors may be an useful tools for management of active RA resistant to
      conventional DMARDs in women who desire to bear children.

PMID- 25765689
TI  - [IL-21 induces regulatory B cell differentiation and immunosuppressive effect
      through cognate interaction with T cells].
AB  - For a long time, it has been thinking that B cells regulate immune responses by
      producing antigen-specific antibodies. However, previous studies have revealed
      that specific B-cell subsets can also negatively regulate T-cell immune
      responses, and have been termed regulatory B cells. Recently, our study showed
      that mouse CD1d(hi)CD5(+) B cell subsets mainly produce IL-10. Therefore, we
      named these populations B10 cells. In our previous studies have also indicated
      that human B10 cells with the ability to express the inhibitory cytokine
      interleukin (IL)-10 have been identified. Although it is rare, B10 cells are
      potent negative regulators of antigen-specific inflammation and T-cell-dependent
      autoimmune diseases in mice. How B10-cell IL-10 production and regulation of
      antigen-specific immune responses are controlled in vivo without inducing
      systemic immunosuppression is unknown. Using an experimental autoimmune
      encephalomyelitis, which is a mouse model for multiple sclerosis, we have shown
      that B10-cell maturation into functional IL-10-secreting effector cells that
      inhibit in vivo autoimmune disease requires IL-21 and CD40-dependent cognate
      interactions with T cells. In addition, the ex vivo provision of CD40 and IL-21
      receptor signals can drive B10-cell development and expansion by four-million
      fold, and generate B10 effector cells producing IL-10 that markedly inhibit
      disease symptoms when transferred into mice with established autoimmune disease.
      The ex vivo expansion and reinfusion of autologous B10 cells may provide a novel
      and effective in vivo treatment for severe autoimmune diseases that are resistant
      to current therapies.

PMID- 25765690
TI  - [Abnormal expression of chemokine receptor on B cells in patients with SLE].
AB  - SLE is a systemic autoimmune disease characterized by overactivation of
      autoreactive memory B cells. However, little is known about the mechanism of
      qualitative abnormality of B cells. The subset classification of T cells by
      expression pattern of master transcription factors and chemokine receptors has
      been established. The biology of T cells is useful information to assess
      qualitative abnormality of B cells. Therefore, we focused on the expression of
      chemokine receptors such as CXCR5 and CXCR3 on B cells in order to define the B
      cell subset classification in patients with SLE. Our results revealed that
      pathological B cells, which lose CXCR5 and express CXCR3, might be involved in
      autoantibody production through the interaction with Tfh cells, and in
      acquisition of effector function of memory B cells during the pathological
      process in SLE. In addition, the results revealed that those effector B cells
      still remained after improvement of disease activity by immunosuppressive
      therapy, indicating that the quantitative abnormality, which is not improved by
      current therapy, may underlie in this disease.

PMID- 25765691
TI  - [Regulatory T cells in systemic lupus erythematosus].
AB  - Autoantibodies are associated with various autoimmune diseases. Systemic lupus
      erythematosus (SLE) is an autoantibody-associated autoimmune disease which
      affects multiple organs. Although both genetic and environmental factors are
      implicated in lupus pathogenesis, the etiology of the disease remains elusive.
      The discovery of CD4(+)CD25(+) regulatory T cells (Tregs) that characteristically
      express forkhead box p3 (Foxp3) gene have greatly advanced our understanding of
      immune systems in autoimmune diseases. CD4(+) Tregs can be classified into two
      main populations: thymus-derived naturally occurring Tregs (nTregs) and induced
      Tregs (iTregs) generated from CD4(+)CD25(-) precursors in the periphery.
      Recently, accumulating evidence suggests that these Tregs play important roles in
      the regulation of humoral immune responses. In this review, we discuss recent
      findings on the role of Tregs in SLE.

PMID- 25765692
TI  - Menstrual cycle corrupts reliable and valid assessment of language dominance:
      Consequences for presurgical evaluation of patients with epilepsy.
AB  - PURPOSE: Functional transcranial Doppler sonography (fTCD) is a valid and non
      invasive tool for determining language dominance, e.g. in the context of
      presurgical evaluations. Beyond this, fTCD might be an ideal tool to study
      dynamics in language dominance over time. However, an essential prerequisite
      would be a high test-retest reliability. This was addressed in the present study.
      METHODS: Test-retest reliability of hemispheric hemodynamics during open speech
      was determined in 11 male and 11 female healthy volunteers using the Animation
      Description Paradigm. Expressive language dominance was assessed weekly over an
      interval of 4-5 weeks. RESULTS: Internal consistency of the four measurements was
      excellent (split-half reliability 0.85-0.95), but test-retest reliability of the
      lateralization index was poor to moderate (rtt=0.37-0.74). Controlling for
      gender, test-retest reliabilities were better in men (rtt=0.67-0.78) as compared
      to women (rtt=0.04-0.70). When arranging the assessments in women around day one
      of menstruation - all were on contraceptives - a significant shift from left
      hemisphere dominance toward bilaterality (t=2.2 p=0.04) was evident around
      menstruation with significant reversal afterwards (t=-3.4 p=0.005). CONCLUSION: A
      high intraindividual variability of language dominance patterns is indicated in
      women when assessed repeatedly by fTCD. Menstrual cycle appeared to be the source
      of inconsistency. The finding challenges the use of non-deactivating methods for
      language dominance assessment in epilepsy. Support for this is demonstrated with
      a female patient with epilepsy in whom language dominance assessed by repeated
      fMRI and fTCD varied concordantly with cycle but not so the repeated
      intracarotidal amobarbital test.

PMID- 25765693
TI  - Interactions between hormones and epilepsy.
AB  - There is a complex, bidirectional interdependence between sex steroid hormones
      and epilepsy; hormones affect seizures, while seizures affect hormones thereby
      disturbing reproductive endocrine function. Both female and male sex steroid
      hormones influence brain excitability. For the female sex steroid hormones,
      progesterone and its metabolites are anticonvulsant, while estrogens are mainly
      proconvulsant. The monthly fluctuations in hormone levels of estrogen and
      progesterone are the basis for catamenial epilepsy described elsewhere in this
      issue. Androgens are mainly anticonvulsant, but the effects are more varied,
      probably because of its metabolism to, among others, estradiol. The mechanisms
      for the effects of sex steroid hormones on brain excitability are related to both
      classical, intracellularly mediated effects, and non-classical membrane effects
      due to binding to membrane receptors. The latter are considered the most
      important in relation to epilepsy. The different sex steroids can also be further
      metabolized within the brain to different neurosteroids, which are even more
      potent with regard to their effect on excitability. Estrogens potentiate
      glutamate responses, primarily by potentiating NMDA receptor activity, but also
      by affecting GABA-ergic mechanisms and altering brain morphology by increasing
      dendritic spine density. Progesterone and its main metabolite 5alpha-pregnan
      3alpha-ol-20-one (3alpha-5alpha-THP) act mainly to enhance postsynaptic GABA
      ergic activity, while androgens enhance GABA-activated currents. Seizures and
      epileptic discharges also affect sex steroid hormones. There are close anatomical
      connections between the temporolimbic system and the hypothalamus controlling the
      endocrine system. Several studies have shown that epileptic activity, especially
      mediated through the amygdala, alters reproductive function, including reduced
      ovarian cyclicity in females and altered sex steroid hormone levels in both
      genders. Furthermore, there is an asymmetric activation of the hypothalamus with
      unilateral amygdala seizures. This may, again, be the basis for the occurrence of
      different reproductive endocrine disorders described for patients with left-sided
      or right-sided temporal lobe epilepsy. 

PMID- 25765694
TI  - India tackles H1N1 influenza outbreak.

PMID- 25765695
TI  - DPP-4 inhibitors and risk of heart failure EXAMINEd.

PMID- 25765696
TI  - Heart failure and mortality outcomes in patients with type 2 diabetes taking
      alogliptin versus placebo in EXAMINE: a multicentre, randomised, double-blind
      trial.
AB  - BACKGROUND: The EXAMINE trial showed non-inferiority of the DPP-4 inhibitor
      alogliptin to placebo on major adverse cardiac event (MACE) rates in patients
      with type 2 diabetes and recent acute coronary syndromes. Concerns about
      excessive rates of in-hospital heart failure in another DPP-4 inhibitor trial
      have been reported. We therefore assessed hospital admission for heart failure in
      the EXAMINE trial. METHODS: Patients with type 2 diabetes and an acute coronary
      syndrome event in the previous 15-90 days were randomly assigned alogliptin or
      placebo plus standard treatment for diabetes and cardiovascular disease
      prevention. The prespecified exploratory extended MACE endpoint was all-cause
      mortality, non-fatal myocardial infarction, non-fatal stroke, urgent
      revascularisation due to unstable angina, and hospital admission for heart
      failure. The post-hoc analyses were of cardiovascular death and hospital
      admission for heart failure, assessed by history of heart failure and brain
      natriuretic peptide (BNP) concentration at baseline. We also assessed changes in
      N-terminal pro-BNP (NT-pro-BNP) from baseline to 6 months. This study is
      registered with ClinicalTrials.gov, number NCT00968708. FINDINGS: 5380 patients
      were assigned to alogliptin (n=2701) or placebo (n=2679) and followed up for a
      median of 533 days (IQR 280-751). The exploratory extended MACE endpoint was seen
      in 433 (16.0%) patients assigned to alogliptin and in 441 (16.5%) assigned to
      placebo (hazard ratio [HR] 0.98, 95% CI 0.86-1.12). Hospital admission for heart
      failure was the first event in 85 (3.1%) patients taking alogliptin compared with
      79 (2.9%) taking placebo (HR 1.07, 95% CI 0.79-1.46). Alogliptin had no effect on
      composite events of cardiovascular death and hospital admission for heart failure
      in the post hoc analysis (HR 1.00, 95% CI 0.82-1.21) and results did not differ
      by baseline BNP concentration. NT-pro-BNP concentrations decreased significantly
      and similarly in the two groups. INTERPRETATION: In patients with type 2 diabetes
      and recent acute coronary syndromes, alogliptin did not increase the risk of
      heart failure outcomes. FUNDING: Takeda Development Center Americas.

PMID- 25765697
TI  - HIV care: ART adherence support and cryptococcal screening.

PMID- 25765699
TI  - Molecular characterization and interactome analysis of Trypanosoma cruzi
      tryparedoxin II.
AB  - Trypanosoma cruzi, the causative agent of Chagas disease, possesses two
      tryparedoxins (TcTXNI and TcTXNII), belonging to the thioredoxin superfamily.
      TXNs are oxidoreductases which mediate electron transfer between trypanothione
      and peroxiredoxins. This constitutes a difference with the host cells, in which
      these activities are mediated by thioredoxins. These differences make TXNs an
      attractive target for drug development. In a previous work we characterized
      TcTXNI, including the redox interactome. In this work we extend the study to
      TcTXNII. We demonstrate that TcTXNII is a transmembrane protein anchored to the
      surface of the mitochondria and endoplasmic reticulum, with a cytoplasmatic
      orientation of the redox domain. It would be expressed during the
      metacyclogenesis process. In order to continue with the characterization of the
      redox interactome of T. cruzi, we designed an active site mutant TcTXNII lacking
      the resolving cysteine, and through the expression of this mutant protein and
      incubation with T. cruzi proteins, heterodisulfide complexes were isolated by
      affinity chromatography and identified by mass spectrometry. This allowed us to
      identify sixteen TcTXNII interacting proteins, which are involved in a wide range
      of cellular processes, indicating the relevance of TcTXNII, and contributing to
      our understanding of the redox interactome of T. cruzi. BIOLOGICAL SIGNIFICANCE:
      T. cruzi, the causative agent of Chagas disease, constitutes a major sanitary
      problem in Latin America. The number of estimated infected persons is ca. 8
      million, 28 million people are at risk of infection and ~20,000 deaths occur per
      year in endemic regions. No vaccines are available at present, and most drugs
      currently in use were developed decades ago and show variable efficacy with
      undesirable side effects. The parasite is able to live and prolipherate inside
      macrophage phagosomes, where it is exposed to cytotoxic reactive oxygen and
      nitrogen species, derived from macrophage activation. Therefore, T. cruzi
      antioxidant mechanisms constitute an active field of investigation, since they
      could provide the basis for a rational drug development. Peroxide detoxification
      in this parasite is achieved by ascorbate peroxidase and different thiol
      dependent peroxidases. Among them, both mitochondrial and cytosolic tryparedoxin
      peroxidases, typical two-cysteine peroxiredoxins, were found to be important for
      hydrogen peroxide and peroxynitrite detoxification and their expression levels
      correlated with parasite infectivity and virulence. In trypanosomes tryparedoxins
      and not thioredoxins act as peroxiredoxin reductases, suggesting that these
      enzymes substitute thioredoxins in these parasites. T. cruzi possesses two
      tryparedoxin genes, TcTXNI and TcTXN II. Since thioredoxins are proteins with
      several targets actively participating of complex redox networks, we have
      previously investigated if this is the case also for TcTXNI, for which we
      described relevant partners (J Proteomics. 2011;74(9):1683-92). In this
      manuscript we investigated the interactions of TcTXNII. We have designed an
      active site mutant tryparedoxin II lacking the resolving cysteine and, through
      the expression of this mutant protein and its incubation with T. cruzi proteins,
      hetero disulfide complexes were isolated by affinity chromatography purification
      and identified by electrophoresis separation and MS identification. This allowed
      us to identify sixteen TcTXNII interacting proteins which are involved in
      different and relevant cellular processes. Moreover, we demonstrate that TcTXNII
      is a transmembrane protein anchored to the surface of the mitochondria and
      endoplasmic reticulum.

PMID- 25765698
TI  - Cryptococcal meningitis screening and community-based early adherence support in
      people with advanced HIV infection starting antiretroviral therapy in Tanzania
      and Zambia: an open-label, randomised controlled trial.
AB  - BACKGROUND: Mortality in people in Africa with HIV infection starting
      antiretroviral therapy (ART) is high, particularly in those with advanced
      disease. We assessed the effect of a short period of community support to
      supplement clinic-based services combined with serum cryptococcal antigen
      screening. METHODS: We did an open-label, randomised controlled trial in six
      urban clinics in Dar es Salaam, Tanzania, and Lusaka, Zambia. From February,
      2012, we enrolled eligible individuals with HIV infection (age >=18 years, CD4
      count of <200 cells per MUL, ART naive) and randomly assigned them to either the
      standard clinic-based care supplemented with community support or standard clinic
      based care alone, stratified by country and clinic, in permuted block sizes of
      ten. Clinic plus community support consisted of screening for serum cryptococcal
      antigen combined with antifungal therapy for patients testing antigen positive,
      weekly home visits for the first 4 weeks on ART by lay workers to provide
      support, and in Tanzania alone, re-screening for tuberculosis at 6-8 weeks after
      ART initiation. The primary endpoint was all-cause mortality at 12 months,
      analysed by intention to treat. This trial is registered with the International
      Standard Randomised Controlled Trial Number registry, number ISCRTN 20410413.
      FINDINGS: Between Feb 9, 2012, and Sept 30, 2013, 1001 patients were randomly
      assigned to clinic plus community support and 998 to standard care. 89 (9%) of
      1001 participants in the clinic plus community support group did not receive
      their assigned intervention, and 11 (1%) of 998 participants in the standard care
      group received a home visit or a cryptococcal antigen screen rather than only
      standard care. At 12 months, 25 (2%) of 1001 participants in the clinic plus
      community support group and 24 (2%) of 998 participants in the standard care
      group had been lost to follow-up, and were censored at their last visit for the
      primary analysis. At 12 months, 134 (13%) of 1001 participants in the clinic plus
      community support group had died compared with 180 (18%) of 998 in the standard
      care group. Mortality was 28% (95% CI 10-43) lower in the clinic plus community
      support group than in standard care group (p=0.004). INTERPRETATION: Screening
      and pre-emptive treatment for cryptococcal infection combined with a short
      initial period of adherence support after initiation of ART could substantially
      reduce mortality in HIV programmes in Africa. FUNDING: European and Developing
      Countries Clinical Trials Partnership.

PMID- 25765700
TI  - Bioactivation of loxoprofen to a pharmacologically active metabolite and its
      disposition kinetics in human skin.
AB  - Loxoprofen (LX) is a prodrug-type non-steroidal anti-inflammatory drug which is
      used not only as an oral drug but also as a transdermal formulation. As a
      pharmacologically active metabolite, the trans-alcohol form of LX (trans-OH form)
      is generated after oral administration to humans. The objectives of this study
      were to evaluate the generation of the trans-OH form in human in vitro skin and
      to identify the predominant enzyme for its generation. In the permeation and
      metabolism study using human in vitro skin, both the permeation of LX and the
      formation of the trans-OH form increased in a time- and dose-dependent manner
      after the application of LX gel to the skin. In addition, the characteristics of
      permeation and metabolism of both LX and the trans-OH form were examined by a
      mathematical pharmacokinetic model. The Km value was calculated to be 10.3 mm in
      the human in vitro skin. The predominant enzyme which generates the trans-OH form
      in human whole skin was identified to be carbonyl reductase 1 (CBR1) by
      immunodepletion using the anti-human CBR1 antibody. The results of the enzyme
      kinetic study using the recombinant human CBR1 protein demonstrated that the Km
      and Vmax values were 7.30 mm and 402 nmol/min/mg protein, respectively. In
      addition, it was found that no unknown metabolites were generated in the human in
      vitro skin. This is the first report in which LX is bioactivated to the trans-OH
      form in human skin by CBR1. Copyright (c) 2015 John Wiley & Sons, Ltd.

PMID- 25765702
TI  - Tunable graphene quantum point contact transistor for DNA detection and
      characterization.
AB  - A graphene membrane conductor containing a nanopore in a quantum point contact
      geometry is a promising candidate to sense, and potentially sequence, DNA
      molecules translocating through the nanopore. Within this geometry, the shape,
      size, and position of the nanopore as well as the edge configuration influences
      the membrane conductance caused by the electrostatic interaction between the DNA
      nucleotides and the nanopore edge. It is shown that the graphene conductance
      variations resulting from DNA translocation can be enhanced by choosing a
      particular geometry as well as by modulating the graphene Fermi energy, which
      demonstrates the ability to detect conformational transformations of a double
      stranded DNA, as well as the passage of individual base pairs of a single
      stranded DNA molecule through the nanopore. 

PMID- 25765703
TI  - Perspectives for Improvement of the Thymic Microenvironment through Manipulation
      of Thymic Epithelial Cells: A Mini-Review.
AB  - Thymic involution during aging is a major reason for the decreased production of
      naive T cells and reduced immunity. Alterations within the thymic
      microenvironment, characterized by the loss of function of thymic epithelial
      cells (TECs) and fibro-adipogenetic transformation, seem to underlie this
      process, mainly through declining communication between thymic stromal cells and
      developing thymocytes. Specifically, the signaling mediated by cytokines and
      hormones secreted by TECs declines during aging. Many therapies based on the
      manipulation of growth factors and hormones have succeeded in partially
      recovering the lymphoid compartment and promoting thymic function. However,
      considering that aging-induced thymic involution is multifactorial, the thymic
      reestablishment achieved with treatments that target isolated pathways is
      incomplete and transitory. Here, we discuss the development of three novel
      approaches for potentially sustained thymic recovery: the induction of sustained
      forkhead box N1 expression, the activation of endogenous thymic epithelial
      progenitor cells (TEPCs), and the generation of TEPCs from pluripotent stem
      cells. Combined approaches targeting both TECs and lymphoid cells will provide a
      potentially more effective strategy for sustained rejuvenation of the thymus. 

PMID- 25765701
TI  - The oak gene expression atlas: insights into Fagaceae genome evolution and the
      discovery of genes regulated during bud dormancy release.
AB  - BACKGROUND: Many northern-hemisphere forests are dominated by oaks. These species
      extend over diverse environmental conditions and are thus interesting models for
      studies of plant adaptation and speciation. The genomic toolbox is an important
      asset for exploring the functional variation associated with natural selection.
      RESULTS: The assembly of previously available and newly developed long and short
      sequence reads for two sympatric oak species, Quercus robur and Quercus petraea,
      generated a comprehensive catalog of transcripts for oak. The functional
      annotation of 91 k contigs demonstrated the presence of a large proportion of
      plant genes in this unigene set. Comparisons with SwissProt accessions and five
      plant gene models revealed orthologous relationships, making it possible to
      decipher the evolution of the oak genome. In particular, it was possible to align
      9.5 thousand oak coding sequences with the equivalent sequences on peach
      chromosomes. Finally, RNA-seq data shed new light on the gene networks underlying
      vegetative bud dormancy release, a key stage in development allowing plants to
      adapt their phenology to the environment. CONCLUSION: In addition to providing a
      vast array of expressed genes, this study generated essential information about
      oak genome evolution and the regulation of genes associated with vegetative bud
      phenology, an important adaptive traits in trees. This resource contributes to
      the annotation of the oak genome sequence and will provide support for forward
      genetics approaches aiming to link genotypes with adaptive phenotypes.

PMID- 25765706
TI  - Abstracts of the Thoracic Society of Australia & New Zealand and the Australian &
      New Zealand Society of Respiratory Science Annual Scientific Meeting 2015, March
      27-April 1, 2015, Queensland, Australia.

PMID- 25765705
TI  - Prediction of respiratory outcome in extremely low gestational age infants.
AB  - BACKGROUND: Bronchopulmonary dysplasia (BPD) is a commonly used outcome for
      randomized neonatal trials. OBJECTIVES: The aim of the present study was to
      determine whether a diagnosis of BPD or respiratory morbidity (RM1 or RM2) at 12
      months corrected age better predicted subsequent RM in extremely low gestational
      age infants (23-28 weeks of gestation). METHODS: Initial analysis was undertaken
      in a development cohort of 76 infants who underwent pulmonary function tests
      (PFTs) at 12 months corrected age. Parents completed infant respiratory diaries 2
      weeks before the PFTs. Analysis was then undertaken in a validation cohort of 227
      infants whose parents completed a 4-week respiratory diary when their infant was
      12 months corrected age. BPD at 28 days (BPD28d) and 36 weeks post-menstrual age
      (BPD36w), RM1 (>=3 days and/or nights of cough, wheeze, and/or medicine use) and
      RM2 (>=4 days and/or nights of cough, wheeze, and/or respiratory medicine use)
      each week for 2 weeks at 12 months corrected age were assessed with regard to
      prediction of respiratory outcomes at 24 months documented by respiratory health
      questionnaires. RESULTS: BPD28d and BPD36w were not significantly associated with
      any respiratory outcome. Areas under the receiver operating characteristic curves
      were significantly better for either definition of RM than BPD28d or BPD36w for
      all outcomes. CONCLUSIONS: RM documented by parental completed diaries at 12
      months corrected age better predicted respiratory outcome at 24 months corrected
      age than BPD regardless of diagnostic criteria.

PMID- 25765704
TI  - Characterization of a novel RXR receptor in the salmon louse (Lepeophtheirus
      salmonis, Copepoda) regulating growth and female reproduction.
AB  - BACKGROUND: Nuclear receptors have crucial roles in all metazoan animals as
      regulators of gene transcription. A wide range of studies have elucidated
      molecular and biological significance of nuclear receptors but there are still a
      large number of animals where the knowledge is very limited. In the present study
      we have identified an RXR type of nuclear receptor in the salmon louse
      (Lepeophtheirus salmonis) (i.e. LsRXR). RXR is one of the two partners of the
      Ecdysteroid receptor in arthropods, the receptor for the main molting hormone 20
      hydroxyecdysone (E20) with a wide array of effects in arthropods. RESULTS: Five
      different LsRXR transcripts were identified by RACE showing large differences in
      domain structure. The largest isoforms contained complete DNA binding domain
      (DBD) and ligand binding domain (LBD), whereas some variants had incomplete or no
      DBD. LsRXR is transcribed in several tissues in the salmon louse including ovary,
      subcuticular tissue, intestine and glands. By using Q-PCR it is evident that the
      LsRXR mRNA levels vary throughout the L. salmonis life cycle. We also show that
      the truncated LsRXR transcript comprise about 50% in all examined samples. We
      used RNAi to knock-down the transcription in adult reproducing female lice. This
      resulted in close to zero viable offspring. We also assessed the LsRXR RNAi
      effects using a L. salmonis microarray and saw significant effects on
      transcription in the female lice. Transcription of the major yolk proteins was
      strongly reduced by knock-down of LsRXR. Genes involved in lipid metabolism and
      transport were also down regulated. Furthermore, different types of growth
      processes were up regulated and many cuticle proteins were present in this group.
      CONCLUSIONS: The present study demonstrates the significance of LsRXR in adult
      female L. salmonis and discusses the functional aspects in relation to other
      arthropods. LsRXR has a unique structure that should be elucidated in the future.

PMID- 25765708
TI  - Chronic Psychological Distress as an Inducer of Microglial Activation and
      Leukocyte Recruitment into the Area Postrema.
AB  - BACKGROUND: Chronic psychological distress can cause neuroinflammation, but the
      involvement of leukocytes in this inflammatory response remains unclear. The area
      postrema (AP) is considered a neural-immune interface because it lacks a blood
      brain barrier and a site for leukocyte recruitment in neuroinflammatory
      conditions induced by immunological insults, but its role in chronic
      psychological distress has not been explored. OBJECTIVE: To determine leukocyte
      recruitment to the AP after chronic psychological distress. METHODS: Rats were
      exposed to cat odor for 5 consecutive days to induce distress, and, on the 6th
      day, their brains were dissected to perform immunohistofluorescence studies of
      the AP. Immune cells were identified and quantified with CD45 and CD11b markers.
      The distribution of neurons and immune cells was determined using TrkA and CD45
      markers, respectively. RESULTS: Distress induced a significant increase in
      CD45(+) and CD11b(+) cells in the AP. Three immunophenotypes were determined in
      the control and distress groups: CD45(+)/CD11b(-), CD45(+)/CD11b(+) and CD45(
      )/CD11b(+). CD expression, morphology and fluorescence intensity enabled the
      identification of different immune cell types: starting from longitudinal
      ramified microglia (mainly in the control group) to amoeboid microglia, monocytes
      and lymphocytes (mostly in the distressed group). TrkA and CD45 expression in the
      AP revealed the proximity between soma neurons and leukocytes. Interestingly,
      some CD45(+) cells expressed TrkA, with increased expression in the distressed
      group. CONCLUSIONS: The identification of microglial activation, leukocyte
      recruitment and the close proximity between neurons and leukocytes in the AP
      after chronic psychological distress exposure suggests the AP as a site for
      distress-induced immune responses and engraftment of leukocytes infiltrating the
      CNS.

PMID- 25765709
TI  - Designing artificial 3D helicates: unprecedented self-assembly of homo
      octanuclear tetrapods with europium.
AB  - Herein, we report on the rational design, preparation and characterization of a
      novel homo-octanuclear helicate, which results from a spatial extension of the
      central tetranuclear platform. The 3D supramolecular assembly is obtained by
      complexing europium(III) with a new hexatopic tripodal ligand. The isolated
      octanuclear helicate is fully characterized by different methods clearly
      evidencing the structure predicted with molecular modelling. The ligand
      preorganization plays a crucial role in a successful self-assembly process and
      induces the formation of a well-defined triple-stranded helical structure. This
      prototypal octanuclear edifice accommodating functional lanthanides within a 3D
      scaffold offers attractive perspectives for further applications. 

PMID- 25765710
TI  - Autoimmune hepatitis: East meets west.
AB  - Autoimmune hepatitis (AIH) is an inflammatory liver disease with diverse clinical
      spectrum, which predominantly affects females. This review provides detailed
      comparisons of epidemiology, genetic predispositions, clinical features, risk
      factors of hepatocellular carcinoma, and mortality in AIH patients between
      eastern and western countries. AIH prevalence and incidence are lower in Asia
      Pacific area than in Europe and America. European and American patients seem to
      have more severe disease, characterized with human leukocyte antigen-DR3
      haplotype, younger age, more AIH-induced "cirrhosis" at diagnosis, higher
      elevated serum immunoglobulin G levels, and positive rate of antisoluble liver
      antigen/liver pancreatitis. The overall AIH diagnostic accuracy of revised
      original criteria and simplified scoring system are similar in European/American
      populations and Asian. Cirrhosis at presentation and non-response to
      immunosuppressive therapy within 1 year are the most important predictors for
      poor prognosis of AIH patients. 

PMID- 25765711
TI  - Mobility and coalescence of stacking fault tetrahedra in Cu.
AB  - Stacking fault tetrahedra (SFTs) are ubiquitous defects in face-centered cubic
      metals. They are produced during cold work plastic deformation, quenching
      experiments or under irradiation. From a dislocation point of view, the SFTs are
      comprised of a set of stair-rod dislocations at the (110) edges of a tetrahedron
      bounding triangular stacking faults. These defects are extremely stable,
      increasing their energetic stability as they grow in size. At the sizes visible
      within transmission electron microscope they appear nearly immobile. Contrary to
      common belief, we show in this report, using a combination of molecular dynamics
      and temperature accelerated dynamics, how small SFTs can diffuse by temporarily
      disrupting their structure through activated thermal events. More over, we
      demonstrate that the diffusivity of defective SFTs is several orders of magnitude
      higher than perfect SFTs, and can be even higher than isolated vacancies.
      Finally, we show how SFTs can coalesce, forming a larger defect in what is a new
      mechanism for the growth of these omnipresent defects. 

PMID- 25765712
TI  - Toll-interacting protein contributes to mortality following myocardial infarction
      through promoting inflammation and apoptosis.
AB  - BACKGROUND AND PURPOSE: Toll-interacting protein (Tollip) is an endogenous
      inhibitor of toll-like receptors, a superfamily that plays a pivotal role in
      various pathological conditions, including myocardial infarction (MI). However,
      the exact role of Tollip in MI remains unknown. EXPERIMENTAL APPROACH: MI models
      were established in Tollip knockout (KO) mice, mice with cardiac-specific
      overexpression of human Tollip gene and in their Tollip(+/+) and non-transgenic
      controls respectively. The effects of Tollip on MI were evaluated by mortality,
      infarct size and cardiac function. Hypoxia-induced cardiomyocyte damage was
      investigated in vitro to confirm the role of Tollip in heart damage. KEY RESULTS:
      Tollip expression was dramatically up-regulated in human ischaemic hearts and
      infarcted mice hearts. MI-induced mortality, infarct size and cardiac dysfunction
      were decreased in Tollip-KO mice compared with Tollip(+/+) controls. Ischaemic
      hearts from Tollip-KO mice exhibited decreased inflammatory cell infiltration and
      reduced NF-kappaB activation. Tollip depletion also alleviated myocardial
      apoptosis by down-regulating pro-apoptotic protein levels and up-regulating anti
      apoptotic protein expressions in infarct border zone. Conversely, MI effects were
      exacerbated in mice with cardiac-specific Tollip overexpression. This aggravated
      MI injury by Tollip in vivo was confirmed with in vitro assays. Inhibition of Akt
      signalling was associated with the detrimental effects of Tollip on MI injury;
      activation of Akt largely reversed the deleterious effects of Tollip on MI
      induced cardiomyocyte death. CONCLUSIONS AND IMPLICATIONS: Tollip promotes
      inflammatory and apoptotic responses after MI, leading to increased mortality and
      aggravated cardiac dysfunction. These findings suggest that Tollip may serve as a
      novel therapeutic target for the treatment of MI.

PMID- 25765713
TI  - Sensitive beta-galactosidase-targeting fluorescence probe for visualizing small
      peritoneal metastatic tumours in vivo.
AB  - Fluorescence-guided diagnostics is one of the most promising approaches for
      facile detection of cancer in situ. Here we focus on beta-galactosidase, which is
      overexpressed in primary ovarian cancers, as a molecular target for visualizing
      peritoneal metastases from ovarian cancers. As existing fluorescence probes are
      unsuitable, we have designed membrane-permeable HMRef-betaGal, in which the
      optimized intramolecular spirocyclic function affords >1,400-fold fluorescence
      enhancement on activation. We confirm that HMRef-betaGal sensitively detects
      intracellular beta-galactosidase activity in several ovarian cancer lines. In
      vivo, this probe visualizes metastases as small as <1 mm in diameter in seven
      mouse models of disseminated human peritoneal ovarian cancer (SHIN3, SKOV3,
      OVK18, OVCAR3, OVCAR4, OVCAR5 and OVCAR8). Because of its high brightness, real
      time detection of metastases with the naked eye is possible. Endoscopic
      fluorescence detection of metastases is also demonstrated. The results clearly
      indicate preclinical potential value of the probe for fluorescence-guided
      diagnosis of peritoneal metastases from ovarian cancers. 

PMID- 25765715
TI  - Unprecedented formation of eta(4)-(vinylketene)iron complexes from eta(4)
      (diene)iron complexes and aromatic compounds in the presence of a Lewis acid.
AB  - A novel and unprecedented formation of eta(4)-(vinylketene)iron complexes from
      eta(4)-(diene)iron complexes is described herein. Treatment of eta(4)-(diene)iron
      complexes with a Lewis acid such as GaCl3 or AlCl3 in the presence of aromatic
      compounds under a CO atmosphere affords eta(4)-(vinylketene)iron complexes via
      electrophilic aromatic substitution. 

PMID- 25765714
TI  - Genome-wide comparative analysis reveals human-mouse regulatory landscape and
      evolution.
AB  - BACKGROUND: Because species-specific gene expression is driven by species
      specific regulation, understanding the relationship between sequence and function
      of the regulatory regions in different species will help elucidate how
      differences among species arise. Despite active experimental and computational
      research, relationships among sequence, conservation, and function are still
      poorly understood. RESULTS: We compared transcription factor occupied segments
      (TFos) for 116 human and 35 mouse TFs in 546 human and 125 mouse cell types and
      tissues from the Human and the Mouse ENCODE projects. We based the map between
      human and mouse TFos on a one-to-one nucleotide cross-species mapper, bnMapper,
      that utilizes whole genome alignments (WGA). Our analysis shows that TFos are
      under evolutionary constraint, but a substantial portion (25.1% of mouse and
      25.85% of human on average) of the TFos does not have a homologous sequence on
      the other species; this portion varies among cell types and TFs. Furthermore,
      47.67% and 57.01% of the homologous TFos sequence shows binding activity on the
      other species for human and mouse respectively. However, 79.87% and 69.22% is
      repurposed such that it binds the same TF in different cells or different TFs in
      the same cells. Remarkably, within the set of repurposed TFos, the corresponding
      genome regions in the other species are preferred locations of novel TFos. These
      events suggest exaptation of some functional regulatory sequences into new
      function. Despite TFos repurposing, we did not find substantial changes in their
      predicted target genes, suggesting that CRMs buffer evolutionary events allowing
      little or no change in the TFos - target gene associations. Thus, the small
      portion of TFos with strictly conserved occupancy underestimates the degree of
      conservation of regulatory interactions. CONCLUSION: We mapped regulatory
      sequences from an extensive number of TFs and cell types between human and mouse
      using WGA. A comparative analysis of this correspondence unveiled the extent of
      the shared regulatory sequence across TFs and cell types under study.
      Importantly, a large part of the shared regulatory sequence is repurposed on the
      other species. This sequence, fueled by turnover events, provides a strong case
      for exaptation in regulatory elements.

PMID- 25765716
TI  - Heat-induced aggregation of thylakoid membranes affect their interfacial
      properties.
AB  - Many of our most popular lipid containing foods are in emulsion form. These foods
      are often highly palatable with high caloric density, that subsequently increases
      the risk of overconsumption and possibly lead to obesity. Regulating the lipid
      bioavailability of high-fat foods is one approach to prevent overconsumption.
      Thylakoids, the chloroplast membrane, creates a barrier around lipid droplets,
      which prolong lipolysis and increase satiety as demonstrated both in animal and
      human studies. However, a reduced lipase inhibiting capacity has been reported
      after heat treatment but the mechanism has not yet been fully established. The
      aim of this study was to investigate thylakoids' emulsifying properties post heat
      treatment and possible links to alterations in lipase inhibiting capacity and
      chlorophyll degradation. Heat-treatment of thylakoids at either 60  degrees C, 75
      degrees C or 90  degrees C for time interval ranging from 15 s to 4 min reduced
      ability to stabilise emulsions, having increased lipid droplets sizes, reduced
      emulsification capacity, and elevated surface load as consequence. Emulsifying
      properties were also found to display a linear relationship to both chlorophyll
      and lipase inhibiting capacity. The correlations support the hypothesis that heat
      treatment induce chlorophyll degradation which promote aggregation within
      proteins inside the thylakoid membrane known to play a decisive role in
      interfacial processes. Therefore, heat-treatment of thylakoids affects both
      chlorophyll content, lipase inhibiting capacity and ability to stabilise the oil
      water interface. Since the thylakoid's appetite reducing properties are a surface
      related phenomenon, the results are useful to optimize the effect of thylakoids
      as an appetite reducing agent. 

PMID- 25765718
TI  - Coherent Control of Nanoscale Ballistic Currents in Transition Metal
      Dichalcogenide ReS2.
AB  - Transition metal dichalcogenides are predicted to outperform traditional
      semiconductors in ballistic devices with nanoscale channel lengths. So far,
      experimental studies on charge transport in transition metal dichalcogenides are
      limited to the diffusive regime. Here we show, using ReS2 as an example, all
      optical injection, detection, and coherent control of ballistic currents. By
      utilizing quantum interference between one-photon and two-photon interband
      transition pathways, ballistic currents are injected in ReS2 thin film samples by
      a pair of femtosecond laser pulses. We find that the current decays on an
      ultrafast time scale, resulting in an electron transport of only a fraction of
      one nanometer. Following the relaxation of the initially injected momentum,
      backward motion of the electrons for about 1 ps is observed, driven by the
      Coulomb force from the oppositely moved holes. We also show that the injected
      current can be controlled by the phase of the laser pulses. These results
      demonstrate a new platform to study ballistic transport of nonequilibrium
      carriers in transition metal dichalcogenides. 

PMID- 25765717
TI  - Expression and significance of circulating microRNA-31 in lung cancer patients.
AB  - BACKGROUND: The aim of this study was to investigate the expression level of
      circulating microRNA-31(miRNA-31) in lung cancer patients and its clinical
      significance. MATERIAL AND METHODS: Real-time fluorescent quantitative PCR was
      utilized to detect the circulating miRNA-31 expression levels in 300 lung cancer
      patients and 300 health control subjects. The ROC curve was drawn to evaluate the
      diagnostic value of the circulating miRNA-31 expression levels in lung cancer.
      The 300 lung cancer patients were divided into a miRNA-31 low-expression group
      and a miRNA-31 high-expression group. A survival curve was drawn according to the
      Kaplan-Meier method to evaluate the prognostic value of the circulating microRNA
      31 expression levels for lung cancer. RESULTS: The circulating miRNA-31
      expression levels in the lung cancer patients (l.88+/-0. 67) increased
      significantly (P<0.001) compared to the healthy controls (0.58+/-0. 44). The area
      under the ROC curve drawn according to the circulating miRNA-31 expression levels
      was 0.785 (95% CI=0.486-0.763). When the critical value was 1.27, the sensitivity
      and specificity for lung cancer diagnosis according to the circulating miRNA-31
      expression levels were 0.769 and 0.745, respectively. The difference in the
      survival curve between the miRNA-31 low-expression group (123 cases) and high
      expression group (177 cases) was statistically significant (P=0.004). Median
      survival period of the low-expression group (38.44 months) was longer than that
      of the high-expression group (25.23 months). CONCLUSIONS: miRNA-31 may be a
      molecular marker for the diagnostic and prognostic evaluation of primary lung
      cancer.

PMID- 25765719
TI  - Distribution of Resistant Esophageal Adenocarcinoma in the Resected Specimens of
      Clinical Stage III Patients after Chemoradiation: Its Clinical Implications.
AB  - BACKGROUND: We have limited knowledge of the geographic distribution of resistant
      esophageal adenocarcinoma (EAC) in resected specimens, but its clinical
      importance can be enormous. METHOD: We selected patients with baseline stage III
      EAC who had had chemoradiation followed by surgery and had residual EAC
      (resistant cases only). Outcomes were correlated with various endpoints
      (percentage of resistant EAC and anatomic distribution). RESULTS: A total of 100
      clinical stage III patients were studied; 90% had an R0 resection, and 99% had
      either moderate or poorly differentiated EAC. Twelve percent had >50% residual
      cancer, 31% had 11-50% residual cancer, 53% had 1-10% residual cancer, and 3% had
      positive nodes only. Each compartment was frequently involved: mucosa/submucosa
      (66%), muscularis propria (76%), and serosa (62%); all compartments were involved
      in 35% of the cases. Lack of EAC (meaning response) was observed in the
      mucosa/submucosa (34%), muscularis propria (24%), serosa (38%), and nodes (42%).
      Although the endoscopic biopsies prior to surgery showed no EAC in 79% of the
      patients, in the surgical specimens, resistant EAC was frequently occurring in
      the mucosa/submucosa (66%). CONCLUSION: Contrary to our hypothesis that resistant
      EAC would be frequent in the nodes, our data show that its distribution is
      heterogeneous and unpredictable. Most importantly, the postchemoradiation
      biopsies are misleading, and a decision to delay/avoid surgery based on negative
      biopsies can be detrimental for the patients.

PMID- 25765721
TI  - Restoring SIRT6 Expression in Hutchinson-Gilford Progeria Syndrome Cells Impedes
      Premature Senescence and Formation of Dysmorphic Nuclei.
AB  - OBJECTIVES: Mice overexpressing SIRT6 live longer than wild-type mice while SIRT6
      knockout mice exhibit similar degenerative phenotypes as individuals with
      Hutchinson-Gilford progeria syndrome (HGPS). Thus, we sought to test whether
      levels of SIRT6 are reduced in cells from individuals with HGPS and whether
      restored SIRT6 expression may impede premature aging phenotypes. METHODS: Levels
      of endogenous SIRT6 and progerin in HGPS and normal fibroblasts were assessed by
      Western blotting and immunofluorescence. A tetracycline-inducible system was
      utilized to test whether progerin causes a rapid reduction in SIRT6 protein.
      SIRT6 was overexpressed in HGPS cells via lentiviral infection with biological
      endpoints including senescence-associated beta-galactosidase (SA-beta-gal)
      positivity, frequency of nuclear atypia, the number of 53BP1-positive DNA damage
      foci and growth rates. RESULTS: Typical HGPS fibroblasts express lower levels of
      SIRT6 than fibroblasts from normal and atypical HGPS donors. Experimental
      induction of progerin did not cause a detectable reduction of SIRT6 protein.
      However, overexpression of SIRT6 in HGPS cells was associated with a reduced
      frequency of SA-beta-gal positivity, fewer misshapen nuclei, fewer DNA damage
      foci, and increased growth rates. CONCLUSIONS: Typical HGPS fibroblasts exhibit
      reduced levels of SIRT6 protein via a mechanism that remains to be elucidated.
      Our findings suggest that restoring SIRT6 expression in HGPS cells may partially
      impede senescence and the formation of dysmorphic nuclei. (c) 2015 S. Karger AG,
      Basel.

PMID- 25765720
TI  - Counterregulatory responses to hypoglycemia differ between glimepiride and
      glyburide in non diabetic individuals.
AB  - OBJECTIVE: Reported rates of hypoglycemia in patients with type 2 diabetes
      mellitus are lower with glimepiride as compared to glyburide. The aim of this
      study was to determine whether physiologic differences in counterregulatory
      neuroendocrine and metabolic mechanisms during hypoglycemia provide a basis for
      the observed clinical differences between glimepiride and glyburide. RESEARCH
      DESIGN AND METHODS: Non-diabetic volunteers (age 38+/-2years, BMI 26+/-1kg/m(2))
      were studied in a single-blind fashion during separate 2day randomized protocols
      consisting of 2h hyperinsulinemic (9pmol/kg/min) euglycemic (4.9+/-0.1mmol) and
      hypoglycemic (2.9+/-0.1mmol/L) clamps. Individuals received biologically
      equivalent doses of glimepiride (4mg) or glyburide (10mg) 1h prior to each
      glucose clamp (n=11) as well as a control group of placebo studies. Glucose
      kinetics were calculated using D-Glucose-6-6d2. RESULTS: Insulin and C-peptide
      levels were increased (p<0.05) during euglycemia in both sulfonylurea groups as
      compared to placebo. However, despite equivalent hypoglycemia, insulin and C
      peptide levels were higher (p<0.05) only after glyburide. Glucagon responses and
      endogenous glucose production (EGP) were decreased (p<0.05) during hypoglycemia
      following glyburide administration as compared to glimepiride. Glyburide reduced
      (p<0.05) norepinephrine responses during euglycemic clamps. In addition combined
      epinephrine and norepinephrine responses during hypoglycemia were reduced
      (p<0.05) following glyburide as compared to placebo. Leptin levels fell by a
      greater amount (p<0.05) during hypoglycemia with both sulfonylureas as compared
      to placebo. CONCLUSIONS: In summary, glimepiride and glyburide can both similarly
      increase insulin and C-peptide levels during hyperinsulinemic euglycemia.
      However, during moderate hyperinsulinemic hypoglycemia (2.9mmol/L) glyburide
      resulted in increased C-peptide and insulin, but blunted glucagon, sympathetic
      nervous system and EGP responses. We conclude that glyburide can acutely reduce
      key neuroendocrine and metabolic counterregulatory defenses during hypoglycemia
      in healthy individuals.

PMID- 25765722
TI  - The evolution of acceptance and tolerance in hosts of avian brood parasites.
AB  - Avian brood parasites lay their eggs in the nests of their hosts, which rear the
      parasite's progeny. The costs of parasitism have selected for the evolution of
      defence strategies in many host species. Most research has focused on resistance
      strategies, where hosts minimize the number of successful parasitism events using
      defences such as mobbing of adult brood parasites or rejection of parasite eggs.
      However, many hosts do not exhibit resistance. Here we explore why some hosts
      accept parasite eggs in their nests and how this is related to the virulence of
      the parasite. We also explore the extent to which acceptance of parasites can be
      explained by the evolution of tolerance; a strategy in which the host accepts the
      parasite but adjusts its life history or other traits to minimize the costs of
      parasitism. We review examples of tolerance in hosts of brood parasites (such as
      modifications to clutch size and multi-broodedness), and utilize the literature
      on host-pathogen interactions and plant herbivory to analyse the prevalence of
      each type of defence (tolerance or resistance) and their evolution. We conclude
      that (i) the interactions between brood parasites and their hosts provide a
      highly tractable system for studying the evolution of tolerance, (ii) studies of
      host defences against brood parasites should investigate both resistance and
      tolerance, and (iii) tolerance and resistance can lead to contrasting
      evolutionary scenarios. 

PMID- 25765723
TI  - Systolic blood pressure and mortality after stroke: too low, no go?
AB  - BACKGROUND AND PURPOSE: Recent studies suggest a J-shaped association between
      systolic blood pressure (SBP) and cardiovascular events. The optimal SBP target
      after stroke remains unknown. We assessed the link between SBP and mortality
      after stroke. METHODS: We included adults (>=20 years) with self-reported stroke
      who participated in the National Health and Nutrition Examination Surveys 1998 to
      2004, with mortality assessment in 2006. Baseline SBP was categorized as low to
      normal (<120 mm Hg), normal (120-140 mm Hg), and high (>=140 mm Hg). Independent
      relationships between baseline SBP and all-cause and vascular mortality were
      assessed using Cox proportional hazards. RESULTS: Of 31 126 adult participants,
      455 had self-reported stroke and baseline BP readings: 19% had low to normal, 31%
      had normal, and 50% had high SBP. Two years after assessment, the low to normal
      SBP group tended to have the highest cumulative all-cause mortality (11.5%),
      compared with mortality rates of 8.5% and 7.5% in the normal and high SBP groups,
      respectively. Similar patterns were seen with vascular mortality. After adjusting
      for covariates, compared with the high SBP group, the low to normal group had
      higher all-cause mortality (adjusted hazard ratio, 1.96; 95% confidence interval,
      1.13-3.39; P=0.017) and trended toward higher vascular mortality (adjusted hazard
      ratio, 2.08; 95% confidence interval, 0.93-4.68; P=0.075). Compared with the
      normal BP group, the risk of all-cause and vascular mortality trended higher in
      low to normal BP group but did not achieve statistical significance. CONCLUSIONS:
      After stroke, compared with SBP in the high range, low to normal SBP is
      associated with poorer mortality outcomes.

PMID- 25765724
TI  - Infarct volume-based subgroup selection in acute ischemic stroke trials.
AB  - BACKGROUND AND PURPOSE: We investigated whether hyperintensities with a diameter
      of at least 3, 3.5, and 4 cm and visible on at least 3 slices on diffusion
      weighted imaging enables patient selection with an infarct volume of >=15 mL.
      METHODS: Consecutive acute stroke patients were screened for the AXIS2 trial and
      examined according to a standardized magnetic resonance imaging protocol in 65
      sites. Diffusion-weighted lesion diameters were measured and compared with
      volumetric assessments. RESULTS: Out of 238 patients, 86.2% (N=206) had infarct
      diameter of at least 3 cm. Volumetric assessments showed infarct volume of >=15
      mL in 157 patients. A cut-off value of 3 cm led to 96.8% sensitivity and 33.3%
      specificity for predicting lesion volume of >=15 mL. Analogously, a 3.5 cm cut
      off led to 96.8% sensitivity and 50.6% specificity and a 4 cm cut-off led to
      91.7% sensitivity and 61.7% specificity. CONCLUSIONS: Lesion diameter measures
      may enable multicentric patient recruitment with a prespecified minimal infarct
      volume. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique
      identifier: NCT00927836.

PMID- 25765725
TI  - Preexisting Serum Autoantibodies Against the NMDAR Subunit NR1 Modulate Evolution
      of Lesion Size in Acute Ischemic Stroke.
AB  - BACKGROUND AND PURPOSE: Recently, we reported high seroprevalence (age-dependent
      up to >19%) of N-methyl-d-aspartate-receptor subunit NR1 (NMDAR1) autoantibodies
      in both healthy and neuropsychiatrically ill subjects (N=4236). Neuropsychiatric
      syndrome relevance was restricted to individuals with compromised blood-brain
      barrier, for example, apolipoprotein E4 (APOE4) carrier status, both clinically
      and experimentally. We now hypothesized that these autoantibodies may upon stroke
      be protective in individuals with hitherto intact blood-brain barrier, but
      harmful for subjects with chronically compromised blood-brain barrier. METHODS:
      Of 464 patients admitted with acute ischemic stroke in the middle cerebral artery
      territory, blood for NMDAR1 autoantibody measurements and APOE4 carrier status as
      indicator of a preexisting leaky blood-brain barrier was collected within 3 to 5
      hours after stroke. Evolution of lesion size (delta day 7-1) in diffusion
      weighted magnetic resonance imaging was primary outcome parameter. In subgroups,
      NMDAR1 autoantibody measurements were repeated on days 2 and 7. RESULTS: Of all
      464 patients, 21.6% were NMDAR1 autoantibody-positive (immunoglobulin M, A, or G)
      and 21% were APOE4 carriers. Patients with magnetic resonance imaging data
      available on days 1 and 7 (N=384) were divided into 4 groups according to NMDAR1
      autoantibody and APOE4 status. Groups were comparable in all stroke-relevant
      presenting characteristics. The autoantibody+/APOE4- group had a smaller mean
      delta lesion size compared with the autoantibody-/APOE4- group, suggesting a
      protective effect of circulating NMDAR1 autoantibodies. In contrast, the
      autoantibody+/APOE4+ group had the largest mean delta lesion area. NMDAR1
      autoantibody serum titers dropped on day 2 and remounted by day 7. CONCLUSIONS:
      Dependent on blood-brain barrier integrity before an acute ischemic brain injury,
      preexisting NMDAR1 autoantibodies seem to be beneficial or detrimental.

PMID- 25765727
TI  - Cerebrovascular disease, amyloid plaques, and dementia.

PMID- 25765726
TI  - B-type natriuretic peptides help in cardioembolic stroke diagnosis: pooled data
      meta-analysis.
AB  - BACKGROUND AND PURPOSE: Determining the underlying cause of stroke is important
      to optimize secondary prevention treatment. Increased blood levels of natriuretic
      peptides (B-type natriuretic peptide/N-terminal pro-BNP [BNP/NT-proBNP]) have
      been repeatedly associated with cardioembolic stroke. Here, we evaluate their
      clinical value as pathogenic biomarkers for stroke through a literature
      systematic review and individual participants' data meta-analysis. METHODS: We
      searched publications in PubMed database until November 2013 that compared BNP
      and NT-proBNP circulating levels among stroke causes. Standardized individual
      participants' data were collected to estimate predictive values of BNP/NT-proBNP
      for cardioembolic stroke. Dichotomized BNP/NT-proBNP levels were included in
      logistic regression models together with clinical variables to assess the
      sensitivity and specificity to identify cardioembolic strokes and the additional
      value of biomarkers using area under the curve and integrated discrimination
      improvement index. RESULTS: From 23 selected articles, we collected information
      of 2834 patients with a defined cause. BNP/NT-proBNP levels were significantly
      elevated in cardioembolic stroke until 72 hours from symptoms onset. Predictive
      models showed a sensitivity >90% and specificity >80% when BNP/NT-proBNP were
      added considering the lowest and the highest quartile, respectively. Both
      peptides also increased significantly the area under the curve and integrated
      discrimination improvement index compared with clinical models. Sensitivity,
      specificity, and precision of the models were validated in 197 patients with
      initially undetermined stroke with final pathogenic diagnosis after ancillary
      follow-up. CONCLUSIONS: Natriuretic peptides are strongly increased in
      cardioembolic strokes. Future multicentre prospective studies comparing BNP and
      NT-proBNP might aid in finding the optimal biomarker, the best time point, and
      the optimal cutoff points for cardioembolic stroke identification.

PMID- 25765728
TI  - Highly textured and transparent RF sputtered Eu2O3 doped ZnO films.
AB  - Background : Zinc oxide (ZnO) is a wide, direct band gap II-VI oxide
      semiconductor. ZnO has large exciton binding energy at room temperature, and it
      is a good host material for obtaining visible and infrared emission of various
      rare-earth ions. Methods : Europium oxide (Eu2O3) doped ZnO films are prepared on
      quartz substrate using radio frequency (RF) magnetron sputtering with doping
      concentrations 0, 0.5, 1, 3 and 5 wt%. The films are annealed in air at a
      temperature of 773 K for 2 hours. The annealed films are characterized using X
      ray diffraction (XRD), micro-Raman spectroscopy, atomic force microscopy,
      ultraviolet (UV)-visible spectroscopy and photoluminescence (PL) spectroscopy.
      Results : XRD patterns show that the films are highly c-axis oriented exhibiting
      hexagonalwurtzite structure of ZnO. Particle size calculations using Debye
      Scherrer formula show that average crystalline size is in the range 15-22 nm
      showing the nanostructured nature of the films. The observation of low- and high
      frequency E2 modes in the Raman spectra supports the hexagonal wurtzite structure
      of ZnO in the films. The surface morphology of the Eu2O3 doped films presents
      dense distribution of grains. The films show good transparency in the visible
      region. The band gaps of the films are evaluated using Tauc plot model. Optical
      constants such as refractive index, dielectric constant, loss factor, and so on
      are calculated using the transmittance data. The PL spectra show both UV and
      visible emissions. Conclusion : Highly textured, transparent, luminescent Eu2O3
      doped ZnO films have been synthesized using RF magnetron sputtering. The good
      optical and structural properties and intense luminescence in the ultraviolet and
      visible regions from the films suggest their suitability for optoelectronic
      applications. 

PMID- 25765729
TI  - Nonoperative treatment improves pain irrespective of radiographic severity. A
      cohort study of 1,414 patients with knee osteoarthritis.
AB  - BACKGROUND AND PURPOSE: The discrepancy between symptoms and radiographic
      severity of knee osteoarthritis (OA) is well described. However, little is known
      about whether radiographic severity is predictive of the clinical result of
      nonoperative treatment. We investigated whether radiographic severity and
      treatment type were associated with improvements in pain after nonoperative
      treatment of patients with knee OA. PATIENTS AND METHODS: A 5-year consecutive
      series of patients deemed not eligible for total knee arthroplasty (TKA) by an
      experienced orthopedic surgeon was contacted 1-5 years later. Radiographic
      severity, age, sex, and BMI were registered at the consultation. At follow-up,
      patients were asked to answer a questionnaire on type of treatment and
      improvements in pain after treatment. RESULTS: Of 1,848 patients who were not
      eligible for TKA, 1,414 (77%) completed the follow-up questionnaire (mean age 66
      (24-96) years; 55% women). Radiographic severity was not associated with
      improvements in pain even after adjusting for treatment type, age, sex, and BMI
      (p > 0.1). The odds ratio of improvement was higher by a factor of 2 in patients
      who received physiotherapy or multimodal treatment than in patients who did not.
      INTERPRETATION: Radiographic severity was not associated with improvements in
      pain after nonoperative treatment. Patients who are not eligible for TKA can
      confidently be referred to nonoperative treatment even if they have severe
      radiographic OA. The treatment should preferably be multimodal, including
      physiotherapy, as recommended in Danish and international clinical guidelines.

PMID- 25765730
TI  - Critically ill patients requiring acute renal replacement therapy are at an
      increased risk of long-term renal dysfunction, but rarely receive specialist
      nephrology follow-up.
AB  - BACKGROUND: Episodes of acute kidney injury (AKI) have been associated with the
      development of chronic kidney disease (CKD). However, follow-up pathways for
      patients who have survived AKI complicating critical illness are not well
      established. We hypothesised that patients who had AKI requiring renal
      replacement therapy (RRT) in intensive care are at risk of CKD, but are rarely
      referred for nephrology follow-up at hospital discharge. METHODS: We performed a
      retrospective analysis of all patients who survived AKI requiring renal
      replacement therapy in intensive care units (ICUs) in the East London region,
      examining renal function at baseline, hospital discharge and 3-6 months follow
      up. We excluded patients who were known to renal services prior to index
      admission. RESULTS: From 5,544 critical care admissions, we identified 219
      patients who survived to be discharged, having undergone RRT for AKI, that were
      not previously known to renal services. Of these, 124 (57%) had creatinine
      measured within 3-6 months after discharge, 104 having a pre-morbid baseline for
      comparison. Only 26 patients (12%) received specialist nephrology follow-up. At 3
      6 months follow-up, the estimated glomerular filtration rate was significantly
      lower than baseline (48 vs. 60 ml/min/1.73 m(2); p < 0.001), with the prevalence
      of CKD stage III-V rising from 49 to 70% (p < 0.001). CONCLUSIONS: Follow-up of
      patients who required RRT for AKI in ICU is inconsistent despite evidence of a
      significant increase in the prevalence of CKD. There is strong justification for
      the development of robust pathways to identify survivors of AKI in order to
      detect and manage CKD and its complications.

PMID- 25765731
TI  - Graphene oxide electrocatalyst on MnO2 air cathode as an efficient electron pump
      for enhanced oxygen reduction in alkaline solution.
AB  - Graphene oxide (GO) was deposited on the surface of a MnO2 air cathode by thermal
      evaporation at 50 degrees C from a GO colloidal suspension. Fourier transformed
      infrared spectroscopy and field emission scanning electron microscopy confirmed
      the presence of GO on the MnO2 air cathode (GO-MnO2). Voltammetry and chrono
      amperometry showed increased currents for the oxygen reduction reaction (ORR) in
      6 M KOH solution for GO-MnO2 compared to the MnO2 cathode. The GO-MnO2 was used
      as an air cathode in an alkaline tin-air cell and produced a maximum power
      density of 13 mW cm(-2), in contrast to MnO2, which produced a maximum power
      density of 9.2 mW cm(-2). The electrochemical impedance spectroscopy results
      suggest that the chemical step for the ORR is the rate determining step, as
      proposed earlier by different researchers. It is suggested that the presence of
      GO and electrochemically reduced graphene oxide (ERGO) on the MnO2 surface are
      responsible for the increased rate of this step, whereby GO and ERGO accelerate
      the process of electron donation to the MnO2 and to adsorbed oxygen atoms. 

PMID- 25765733
TI  - IgE sensitization to lupine in bakers - cross-reactivity or co-sensitization to
      wheat flour?
AB  - BACKGROUND: Food allergy to lupine has frequently been reported in patients
      allergic to peanut or soy, and cross-reactivity between these legumes is known.
      Moreover, respiratory allergy to lupine has been described after inhalation,
      mostly at workplaces. Our aim was to study the frequency of lupine sensitization
      in European bakers with suspected bakers' allergy. Furthermore, associations
      between sensitizations to lupine and other plant allergens were investigated.
      METHODS: One hundred and sixteen bakers with work-related allergic symptoms but
      without known food allergies were examined. Specific IgE (sIgE) antibodies to
      wheat flour, rye flour, lupine, peanut, soy and the recombinant single birch
      protein rBet v 1 were quantified. Selected sera were tested for cross-reactivity
      using ImmunoCAP inhibition and ISAC microarrays. RESULTS: Whereas 67% of bakers
      were sensitized to wheat and/or rye flour, 35% showed sIgE to peanut and 33% to
      lupine. All lupine-positive bakers also had sIgE to either wheat flour (89%)
      and/or peanut (92%), and lupine sIgE correlated significantly with sIgE to
      peanut, soy, wheat and rye flour. Used as an inhibitor, wheat flour inhibited IgE
      binding to lupine in 4 out of 8 sera, indicating cross-reactivity. In
      microarrays, these sera showed IgE binding to lipid transfer proteins, profilins
      and/or cross-reactive carbohydrate determinants. Further inhibition experiments
      suggest that these single allergens are involved in cross-reactivity. CONCLUSION:
      One third of 116 symptomatic bakers showed sIgE to lupine. At least some of these
      sensitizations were based on cross-reactivity between lupine and wheat flour.
      However, the considerable sensitization rate could also be a sign that the use of
      lupine flour in bakeries may be of occupational relevance.

PMID- 25765732
TI  - Role of nucleus of the solitary tract noradrenergic neurons in post-stress
      cardiovascular and hormonal control in male rats.
AB  - Chronic stress causes hypothalamo-pituitary-adrenal (HPA) axis hyperactivity and
      cardiovascular dyshomeostasis. Noradrenergic (NA) neurons in the nucleus of the
      solitary tract (NTS) are considered to play a role in these changes. In this
      study, we tested the hypothesis that NTS NA A2 neurons are required for
      cardiovascular and HPA axis responses to both acute and chronic stress. Adult
      male rats received bilateral microinjection into the NTS of 6-hydroxydopamine (6
      OHDA) to lesion A2 neurons [cardiovascular study, n = 5; HPA study, n = 5] or
      vehicle [cardiovascular study, n = 6; HPA study, n = 4]. Rats were exposed to
      acute restraint stress followed by 14 d of chronic variable stress (CVS). On the
      last day of testing, rats were placed in a novel elevated plus maze (EPM) to test
      post-CVS stress responses. Lesions of NTS A2 neurons reduced the tachycardic
      response to acute restraint, confirming that A2 neurons promote sympathetic
      activation following acute stress. In addition, CVS increased the ratio of low
      frequency to high-frequency power for heart rate variability, indicative of
      sympathovagal imbalance, and this effect was significantly attenuated by 6-OHDA
      lesion. Lesions of NTS A2 neurons reduced acute restraint-induced corticosterone
      secretion, but did not affect the corticosterone response to the EPM, indicating
      that A2 neurons promote acute HPA axis responses, but are not involved in CVS
      mediated HPA axis sensitization. Collectively, these data indicate that A2
      neurons promote both cardiovascular and HPA axis responses to acute stress.
      Moreover, A2 catecholaminergic neurons may contribute to the potentially
      deleterious enhancement of sympathetic drive following chronic stress. 

PMID- 25765734
TI  - First report of L1014F kdr mutation in Culex quinquefasciatus in Mexico.
AB  - The L1014F mutation in the voltage-sodium channel gene has been associated with
      resistance to DDT and pyrethroids in various arthropod species including
      mosquitoes. We determined the frequency of the L1014F kdr mutation in 16 field
      populations of Culex quinquefasciatus from Northeastern Mexico collected between
      2008 and 2013. The L1014F was present in all populations analyzed with the lowest
      frequency (3.33%) corresponding to the population from Monclova collected in
      2012, and the highest frequency (63.63%) from the Monterrey population collected
      in 2012. The presence of a kdr mutation in populations of Cx. quinquefasciatus
      from northeastern Mexico provides evidence of pyrethroid resistance. This
      requires a special attention, considering that pyrethroid-based insecticides are
      commonly used in vector-control campaigns, especially against Aedes aegypti (L.).

PMID- 25765735
TI  - The range of validity of sorption kinetic models.
AB  - Several hundred papers are published yearly reporting liquid-phase adsorption
      kinetics data. In general the data is analyzed using a variety of standard models
      such as the pseudo first- and second-order models and the Intraparticle-Diffusion
      model. The validity of these models is often assessed empirically via their
      ability to fit the data, independently of their physicochemical soundness. The
      aim of the present paper is to rationalize the analysis of liquid-phase
      adsorption kinetics data, and to investigate experimental factors that influence
      the adsorption kinetics, in addition to the characteristics of the adsorbent
      material itself. For that purpose we use a simple Langmuir adsorption-diffusion
      model, which enables us to identify three dimensionless numbers that characterize
      the working regime of any batch adsorption experiment: an adsorption Thiele
      modulus, a saturation modulus, and a loading modulus. The standard models are
      found to be particular cases of the general adsorption-diffusion model for
      specific values of the dimensionless numbers. This provides sound physicochemical
      criteria for the validity of the models. Based on our modeling, we also propose a
      general yet simple data analysis procedure to practically estimate the diffusion
      coefficient in adsorbent pellets starting from adsorption half-times. 

PMID- 25765736
TI  - Highly effective adsorption of cationic and anionic dyes on magnetic Fe/Ni
      nanoparticles doped bimodal mesoporous carbon.
AB  - Magnetic Fe/Ni nanoparticles doped bimodal mesoporous carbon (MBMC) was prepared
      for highly effective adsorption of cationic dye methylene blue (MB) and anionic
      dye methyl orange (MO). Structure characterization demonstrated that Fe/Ni
      nanoparticles were embedded into the interior of the mesoprous carbon, and MBMC
      maintained ordered and bimodal mesopores. The effects of several parameters such
      as contact time, pH, temperature, ionic strength and dye molecular structure on
      the adsorption were investigated. Alkaline pH was better for MB adsorption, while
      acidic pH was more favorable for MO uptake. The adsorption capacity was slightly
      enhanced when existing ion concentrations increased. Adsorption on MBMC was
      affected by the molecular structures of different dyes, and both primary and
      secondary pores of MBMC were involved in dye adsorption. The adsorption kinetics
      fitted well with pseudo-second-order model and exhibited 3-stage intraparticle
      diffusion mode. Equilibrium data were best described by Langmuir model, and the
      estimated maximum adsorption capacity for MB and MO was 959.5mg/g and 849.3mg/g,
      respectively. Thermodynamic studies indicated that the adsorption process was
      spontaneous and endothermic. Moreover, the adsorbent could be regenerated using
      ethanol, and the regenerated adsorbent after seven cycles could retain over 80%
      of the adsorption capacity for the fresh adsorbent. The results suggested that
      MBMC could be considered as very effective and promising materials for both
      anionic and cationic dyes removal from wastewater. 

PMID- 25765737
TI  - Editorial overview: Biocatalysis and biotransformation: bio-inspired, bio-based
      and bio-linked catalysis.

PMID- 25765738
TI  - TLR2/6 agonists and interferon-gamma induce human melanoma cells to produce
      CXCL10.
AB  - Clinical approaches to treat advanced melanoma include immune therapies, whose
      benefits depend on tumor-reactive T-cell infiltration of metastases. However,
      most tumors lack significant immune infiltration prior to therapy. Selected
      chemokines promote T-cell migration into tumors; thus, agents that induce these
      chemokines in the tumor microenvironment (TME) may improve responses to systemic
      immune therapy. CXCL10 has been implicated as a critical chemokine supporting T
      cell infiltration into the TME. Here, we show that toll-like receptor (TLR)
      agonists can induce chemokine production directly from melanoma cells when
      combined with IFNgamma treatment. We find that TLR2 and TLR6 are widely expressed
      on human melanoma cells, and that TLR2/6 agonists (MALP-2 or FSL-1) synergize
      with interferon-gamma (IFNgamma) to induce production of CXCL10 from melanoma
      cells. Furthermore, melanoma cells and immune cells from surgical specimens also
      respond to TLR2/6 agonists and IFNgamma by upregulating CXCL10 production,
      compared to treatment with either agent alone. Collectively, these data identify
      a novel mechanism for inducing CXCL10 production directly from melanoma cells,
      with TLR2/6 agonists +IFNgamma and raise the possibility that intratumoral
      administration of these agents may improve immune signatures in melanoma and have
      value in combination with other immune therapies, by supporting T-cell migration
      into melanoma metastases. 

PMID- 25765739
TI  - Trigger finger following partial flexor tendon laceration: Magnetic resonance
      imaging-assisted diagnosis.
AB  - INTRODUCTION: Post-traumatic trigger finger is considerably rarer than normal
      trigger finger. The diagnosis is usually made on a clinical basis. This can be
      obscured; however, by concurrent pathological conditions. We report a case of
      post-traumatic trigger finger in which diagnosis was aided by magnetic resonance
      imaging (MRI). PRESENTATION OF CASE: Our patient is a 32-year-old male who had a
      previous laceration with a subsequent surgery for infectious tenosynovitis. The
      MRI showed the impinging tendon tag. Surgical excision of the tag successfully
      solved the case. DISCUSSION: The use of imaging studies for the diagnosis of post
      traumatic trigger finger has been previously reported, the authors described a
      variation on the contour of the pulley system. The full lacerated tendon tag can
      be seen on our patient's MRI. CONCLUSION: On this case, the use of MRI was a
      useful aid for the differential diagnosis of post-traumattic trigger finger.

PMID- 25765740
TI  - Advanced esophageal cancer with tracheobronchial fistula successfully treated by
      esophageal bypass surgery.
AB  - INTRODUCTION: When esophageal cancer infiltrates the respiratory tract and forms
      a fistula, a patient's quality of life falls remarkably. Abstinence from oral
      feeding is necessary to prevent respiratory complications including pneumonia.
      Surgery is sometimes necessary to maintain quality of life. The aim of this study
      was to examine clinical outcomes of esophageal cancer complicated by
      tracheobronchial fistula. PRESENTATION OF CASE: Twelve patients who underwent
      esophageal bypass between 2006 and 2011 in our hospital were studied. Patient
      characteristics, therapeutic course, outcome, and operation type were compared.
      Six patients among 8 who could not tolerate oral feeding could do so after bypass
      surgery. Ten patients were able to enjoy oral intake up until the last few days
      of life. Three patients survived for more than 10 months. In spite of undergoing
      an operation, 1 patient survived for only 2 months and another for 4 months. The
      only complication was postoperative delirium in 1 patient. DISCUSSION: While
      surgical bypass is more invasive than procedures such as endoscopic stenting, we
      had few complications after operative intervention and were able to maintain
      quality of life in our patients. CONCLUSION: This bypass procedure is a treatment
      option for patients with tracheobronchial fistula from advanced esophageal
      cancer.

PMID- 25765741
TI  - Repeated resections for liver metastasis from primary adrenocortical carcinoma: A
      case report.
AB  - INTRODUCTION: Adrenal cortical carcinoma (ACC) is a very rare type of tumor that
      generally has a poor prognosis. Little has been reported on repeated liver
      resections with recurrent metastasis still confined to the liver. In this report,
      we describe a case of functioning ACC in a 65-year-old woman with 2 liver
      metastases of the ACC (at 1.5 and 4 years) after the right adrenalectomy.
      PRESENTATION OF CASE: A 65-year-old woman was referred to our hospital based on a
      suspicion of hyperaldosteronism. Abdominal computed tomography revealed a lesion
      at the right adrenal gland; therefore, we performed right adrenalectomy and
      subsequently diagnosed the lesion as ACC. However, follow-up computed tomography
      at 1.5 and 4 years after the right adrenalectomy revealed liver metastasis of
      ACC; liver resection was performed for both metastases. DISCUSSION: Complete
      surgical resection is the established approach for the treatment of ACC. The
      prognosis of ACC is usually dismal, and recurrence rates of up to 85% have been
      reported. However, the appropriate treatment for recurrent ACC is not well
      established, and the effectiveness of other modalities, such as chemotherapy and
      radiotherapy, is not proven. Therefore, surgical resection may currently be the
      most appropriate treatment modality, as the patient achieved a disease-free
      interval of 2.5 years after the first liver resection. CONCLUSION: In selected
      patients with recurrent or metastatic ACC, resection is likely to be associated
      with prolonged survival. However, a full cure is generally not achievable, and a
      multidisciplinary approach is likely needed to achieve long-term disease-free
      status and survival.

PMID- 25765742
TI  - Au-Rh and Au-Pd nanocatalysts supported on rutile titania nanorods: structure and
      chemical stability.
AB  - Au, Rh, Pd, Au-Rh and Au-Pd nanoparticles (NPs) were synthesized by colloidal
      chemical reduction and immobilized on hydrothermally-prepared rutile titania
      nanorods. The catalysts were characterized by aberration-corrected TEM/STEM, XPS,
      and FTIR, and were evaluated in the hydrogenation of tetralin in the presence of
      H2S. Oxidizing and reducing thermal treatments were employed to remove the
      polyvinyl alcohol (PVA) surfactant. Reduction in H2 at 350  degrees C was found
      efficient for removing the PVA while preserving the size (ca. 3 nm), shape and
      bimetallic nature of the NPs. While Au-Pd NPs are alloyed at the atomic scale, Au
      Rh NPs contain randomly distributed single-phase domains. Calcination-reduction
      of Au-Rh NPs mostly leads to separated Au and Rh NPs, while pre-reduction
      generates a well-defined segregated structure with Rh located at the interface
      between Au and TiO2 and possibly present around the NPs as a thin overlayer. Both
      the titania support and gold increase the resistance of Rh and Pd to oxidation.
      Furthermore, although detrimental to tetralin hydrogenation initial activity,
      gold stabilizes the NPs against surface sulfidation in the presence of 50 ppm
      H2S, leading to increased catalytic performances of the Au-Rh and Au-Pd systems
      as compared to their Rh and Pd counterparts. 

PMID- 25765743
TI  - Intervention among new parents followed up by an interview study exploring their
      experiences of telemedicine after early postnatal discharge.
AB  - BACKGROUND: a move towards earlier postnatal discharge raises the challenge of
      finding new ways to support families when they are discharged early after
      childbirth. AIM: to explore how postnatal parents experienced the use of
      telemedicine following early discharge from hospital (i.e. 24 hours after
      childbirth) by investigating if they consider that their postnatal needs are met,
      and whether or not they experience a sense of security and parental self
      efficacy. DESIGN: intervention followed by a qualitative interview study. The
      intervention took place on a postnatal ward with approximately 1000 births a
      year. An app including chat, a knowledgebase and automated messages was trialled
      between postnatal parents at home and the hospital. Parents had access to the app
      for seven days after discharge. POPULATION: 42 new mothers were recruited from
      the postnatal ward in accordance with the inclusion criteria (i.e. discharged
      within 24 hours of childbirth). Both parents were invited for interview. METHODS:
      42 sets of parents participated in the trial, and 28 sets agreed to be
      interviewed. Interviews (n=28) were conducted with 27 mothers and 11 fathers.
      Parents were interviewed together in 10 cases, 17 mothers were interviewed alone,
      and one father was interviewed alone. The data analysis was inspired by
      systematic text condensation based on Giorgi's descriptive phenomenological
      method. FINDINGS: parents were confident in use of the app, and did not
      experience any barriers in contacting the nurses via asynchronous communication.
      Parents received timely information and guidance by communicating online, and
      felt that their follow-up support needs were met. CONCLUSIONS: parents viewed the
      app as a lifeline, and saw it as a means of informing and guiding them following
      early discharge from hospital after childbirth. As such, this app shows potential
      for enhancing self-efficacy and postnatal sense of security.

PMID- 25765744
TI  - Women's birthplace decision-making, the role of confidence: Part of the
      Evaluating Maternity Units study, New Zealand.
AB  - OBJECTIVE: to explore women's birthplace decision-making and identify the factors
      which enable women to plan to give birth in a freestanding midwifery-led primary
      level maternity unit rather than in an obstetric-led tertiary level maternity
      hospital in New Zealand. DESIGN: a mixed methods prospective cohort design.
      METHODS: data from eight focus groups (37 women) and a six week postpartum survey
      (571 women, 82%) were analysed using thematic analysis and descriptive
      statistics. The qualitative data from the focus groups and survey were the
      primary data sources and were integrated at the analysis stage; and the secondary
      qualitative and quantitative data were integrated at the interpretation stage.
      SETTING: Christchurch, New Zealand, with one tertiary maternity hospital and four
      primary level maternity units (2010-2012). PARTICIPANTS: well (at 'low risk' of
      developing complications), pregnant women booked to give birth in one of the
      primary units or the tertiary hospital. All women received midwifery continuity
      of care, regardless of their intended or actual birthplace. FINDINGS: five core
      themes were identified: the birth process, women's self-belief in their ability
      to give birth, midwives, the health system and birth place. 'Confidence' was
      identified as the overarching concept influencing the themes. Women who chose to
      give birth in a primary maternity unit appeared to differ markedly in their
      beliefs regarding their optimal birthplace compared to women who chose to give
      birth in a tertiary maternity hospital. The women who planned a primary maternity
      unit birth expressed confidence in the birth process, their ability to give
      birth, their midwife, the maternity system and/or the primary unit itself. The
      women planning to give birth in a tertiary hospital did not express confidence in
      the birth process, their ability to give birth, the system for transfers and/or
      the primary unit as a birthplace, although they did express confidence in their
      midwife. KEY CONCLUSIONS AND IMPLICATIONS FOR PRACTICE: birthplace is a
      profoundly important aspect of women's experience of childbirth. Birthplace
      decision-making is complex, in common with many other aspects of childbirth. A
      multiplicity of factors needs converge in order for all those involved to gain
      the confidence required to plan what, in this context, might be considered a
      'countercultural' decision to give birth at a midwife-led primary maternity unit.

PMID- 25765745
TI  - Midwives' decision making about transfers for 'slow' labour in rural New Zealand.
AB  - Midwives who provided Lead Maternity Care (LMC) to women in rural areas were
      invited to share their experiences of decision making around transfer in labour.
      Ethics approval was obtained from the NZ National Ethics Committee. OBJECTIVE: to
      explore midwives' decision making processes when making transfer decisions for
      slow labour progress from rural areas to specialist care. DESIGN: individual and
      group interviews were conducted with a purposive sample of rural midwives. The
      recalled decision processes of the midwives were subjected to a content and
      thematic analysis to expose experiences in common and to highlight aspects of
      probabilistic (normative), heuristic (behavioural), and group decision making
      theory within the rural context. SETTING: New Zealand. PARTICIPANTS: 15 midwives
      who provided LMC services to women in their rural areas. FINDINGS: 'making the
      mind shift', 'sitting on the boundary', 'timing the transfer' and 'the community
      interest' emerged as key themes. The decision processes were also influenced by
      the woman's preferences and the distance and time involved in the transfer. KEY
      CONCLUSIONS AND IMPLICATIONS FOR PRACTICE: the findings contribute insights into
      the challenge of making transfer decisions in rural units; particularly for
      otherwise well women who were experiencing slow labour progress. Knowledge of the
      fallibility of our heuristic decision making strategies may encourage the
      practitioner to step back and take a more deliberative, probabilistic view of the
      situation. In addition to the clinical picture, this process should include the
      relational and aspirational aspects for the woman, and any logistical challenges
      of the particular rural context.

PMID- 25765750
TI  - Approaches to the design of catalytic metallodrugs.
AB  - Metal ions are known to act as catalytic centres in metallo-enzymes. On the other
      hand, low-molecular-weight metal complexes are widely used as catalysts in
      chemical systems. However, small catalysts do not have a large protein ligand to
      provide substrate selectivity and minimize catalyst poisoning. Despite the
      challenges that the lack of a protein ligand might pose, some success in the use
      of metal catalysts for biochemical transformations has been reported. Here, we
      present a brief overview of such reports, especially involving catalytic
      reactions in cells. Examples include C-C bond formation, deprotection and
      functional group modification, degradation of biomolecules, and redox modulation.
      We discuss four classes of catalytic redox modulators: photosensitizers,
      superoxide dismutase mimics, thiol oxidants, and transfer hydrogenation
      catalysts. Catalytic metallodrugs offer the prospect of low-dose therapy and a
      challenging new design strategy for future exploration.

PMID- 25765751
TI  - Hesperetin induces melanin production in adult human epidermal melanocytes.
AB  - One of the major sources of flavonoids for humans are citrus fruits, hesperidin
      being the predominant flavonoid. Hesperetin (HSP), the aglycon of hesperidin, has
      been reported to provide health benefits such as antioxidant, anti-inflammatory
      and anticarcinogenic effects. However, the effect of HSP on skin pigmentation is
      not clear. Some authors have found that HSP induces melanogenesis in murine B16
      F10 melanoma cells, which, if extrapolated to in vivo conditions, might protect
      skin against photodamage. Since the effect of HSP on normal melanocytes could be
      different to that observed on melanoma cells, the described effect of HSP on
      murine melanoma cells has been compared to the effect obtained using normal human
      melanocytes. HSP concentrations of 25 and 50 uM induced melanin synthesis and
      tyrosinase activity in human melanocytes in a concentration-dependent manner.
      Compared to control melanocytes, 25 uM HSP increased melanin production and
      tyrosinase activity 1.4-fold (p < 0.01) and 1.1-fold (p < 0.01), respectively,
      and the corresponding increases in the case of 50 uM HSP were 1.9-fold (p <
      0.001) and 1.3-fold (p < 0.001). Therefore, HSP could be considered a valuable
      photoprotective substance if its capacity to increase melanin production in human
      melanocyte cultures could be reproduced on human skin. 

PMID- 25765752
TI  - Toxic essential oils. Part IV: The essential oil of Achillea falcata L. as a
      source of biologically/pharmacologically active trans-sabinyl esters.
AB  - Herein we report on the comprehensive chemical analysis of the essential oils
      obtained from above- and underground parts of a previously unreported chemotype
      of Achillea falcata L. (Asteraceae) and, for the first time, on the
      biological/toxicological profile of its dominant/newly discovered volatile
      metabolites. Detailed spectral analyses, in combination with chemical synthesis
      and theoretical study, of selected constituents, enabled the identification of
      trans-sabinol and its esters - the formate, tiglate (new compounds), acetate,
      butanoate, isobutanoate, 2-methylbutanoate and 3-methylbutanoate - in both aerial
      and underground parts of A. falcata. Evaluation of acute toxicity in Artemia
      salina model, in vitro and in silico (molecular docking) evaluation of
      acetylcholinesterase inhibitory activity and in vivo (mice) evaluation of
      antinociceptive activity (hot plate, tail immersion and acetylcholine-induced
      abdominal writhing tests) of trans-sabinol and its esters suggested that they may
      interact with different targets in crustacean/mammalian organisms. Alongside
      moderate acute toxicity (LD50 (48 h) = 0.03-0.26 mmol/L), the tested compounds
      exert influence on both the peripheral and central nervous systems (in the hot
      plate test, trans-sabinyl tiglate, at 50 mg/kg, produced a 140% baseline increase
      15 min after the treatment) and to moderately inhibit acetylcholinesterase (at
      the concentration of 20 ug/mL, these compounds caused a reduction of
      acetylcholinesterase activity up to 40%). 

PMID- 25765753
TI  - Relative mortality rates from incident chronic diseases among breast cancer
      survivors--a 14 year follow-up of five-year survivors diagnosed in Denmark
      between 1994 and 2007.
AB  - BACKGROUND: It remains unknown whether incident chronic diseases are more often
      fatal among breast cancer survivors than among women free of breast cancer.
      METHODS: We conducted a nationwide matched cohort study of all Danish breast
      cancer patients diagnosed between 1994 and 2007, who survived for five years. We
      compared their long-term mortality with five times as many women from the general
      population without breast cancer, matched on age. We used time-varying methods to
      compute mortality rate ratios (MRRs) for incident diseases included in the
      Charlson Comorbidity Index (CCI). RESULTS: One third of five-year breast cancer
      survivors developed incident diseases during 14 years of follow-up, with about
      the same incidence as women without breast cancer. Mortality associated with any
      incident disease was similar among breast cancer survivors (MRR = 7.1, 95%
      confidence interval (CI): 6.7, 7.4) and comparison women (MRR = 7.5, 95% CI: 7.3,
      7.7). Among breast cancer patients, relative mortality associated with incident
      diseases was higher among patients treated with chemotherapy (MRR = 10, 95% CI:
      8.7, 12) and radiotherapy (MRR = 9.8, 95% CI: 8.8, 11) than among patients who
      received surgery (MRR = 7.0, 95% CI: 6.7, 7.4) or hormonal therapy (MRR = 6.3,
      95% CI: 5.8, 6.9). CONCLUSION: There were no marked differences in mortality of
      diseases among breast cancer survivors and women from the general population.
      Among breast cancer patients, new diseases were more often fatal in patients
      treated with chemotherapy and radiotherapy. Five-year breast cancer survivors
      have similar risk of dying from new chronic medical conditions as women from the
      general population without breast cancer.

PMID- 25765755
TI  - Serum brain derived neurotrophic factor evaluation in patients with chronic
      schizophrenia.

PMID- 25765754
TI  - Hippocampal neuroligin-2 links early-life stress with impaired social recognition
      and increased aggression in adult mice.
AB  - Early-life stress is a key risk factor for the development of neuropsychiatric
      disorders later in life. Neuronal cell adhesion molecules have been strongly
      implicated in the pathophysiology of psychiatric disorders and in modulating
      social behaviors associated with these diseases. Neuroligin-2 is a synaptic cell
      adhesion molecule, located at the postsynaptic membrane of inhibitory GABAergic
      synapses, and is involved in synaptic stabilization and maturation. Alterations
      in neuroligin-2 expression have previously been associated with changes in social
      behavior linked to psychiatric disorders, including schizophrenia and autism. In
      this study, we show that early-life stress, induced by limited nesting and
      bedding material, leads to impaired social recognition and increased aggression
      in adult mice, accompanied by increased expression levels of hippocampal
      neuroligin-2. Viral overexpression of hippocampal neuroligin-2 in adulthood
      mimics early-life stress-induced alterations in social behavior and social
      cognition. Moreover, viral knockdown of neuroligin-2 in the adult hippocampus
      attenuates the early-life stress-induced behavioral changes. Our results
      highlight the importance of neuroligin-2 in mediating early-life stress effects
      on social behavior and social cognition and its promising role as a novel
      therapeutic target for neuropsychiatric disorders. 

PMID- 25765756
TI  - Estradiol and cortisol interactions in youth externalizing psychopathology.
AB  - Growing evidence has indicated that gonadal and stress hormones interact to shape
      socially dominant behavior and externalizing psychopathology; however, such work
      to date has focused exclusively on the testosterone-cortisol interaction, despite
      expectations that estradiol should be associated with similar behavioral outcomes
      to testosterone. Here, we present the first empirical test of the hypothesis that
      adolescent males and females (N=105, ages 13-18) with high estradiol and low
      cortisol concentrations are at highest risk for externalizing problems, but -
      replicating previous work - only among adolescents high on pathological
      personality traits. Parents reported on youth psychopathology and personality,
      and hormone concentrations were measured via passive drool. Results confirmed the
      hypothesis: high estradiol was associated with more externalizing behaviors, but
      only when cortisol was low and personality traits of disagreeableness and
      emotional instability were high. Further, these associations held when
      controlling for testosterone concentrations. These findings provide the first
      empirical evidence of a hypothalamic pituitary adrenal (HPA)*hypothalamic
      pituitary gonadal (HPG) axis interaction that extends the "dual hormone"
      hypothesis beyond testosterone. 

PMID- 25765757
TI  - Glucocorticoid and mineralocorticoid receptor polymorphisms and recurrence of
      major depressive disorder.
AB  - OBJECTIVE: Previous research found that variants of the glucocorticoid receptor
      (GR) (9beta, ER22/23EK, BclI, TthIIIl, NR3C1-1 and N363S) and mineralocorticoid
      receptor (MR) gene polymorphism (-2 C/G and I180V) are associated with both
      glucocorticoid (GC) sensitivity and major depressive disorder (MDD). There are no
      data which investigated prospectively whether these variants are associated with
      recurrence of MDD. METHODS: Data were derived from the Netherlands Study of
      Depression and Anxiety (NESDA) which used the Composite International Diagnostic
      Interview (CIDI) to determine MDD. Polymorphisms in the GR and MR gene were
      determined and haplotypes were characterized. We analyzed in retrospect whether
      recurrent MDD (n=951) in comparison with first onset MDD (n=919) was associated
      with polymorphisms in the GR and MR gene. Furthermore, we analyzed prospectively
      for 4 years the time to recurrence among 683 subjects with a remitted MDD
      diagnosis. Time to recurrence of MDD was assessed using the CIDI and a life chart
      interview. Additionally, we analyzed interactions of the investigated
      polymorphisms with childhood trauma and recent negative life events. RESULTS: GR
      and MR gene polymorphisms and derived haplotypes were not associated with
      recurrence of depression in both retrospective and prospective analyses. In
      addition, no consistent interactions between GR and MR polymorphisms and
      childhood trauma or life events were found. CONCLUSION: This study did not find
      consistent associations between GR and MR gene polymorphisms, interactions
      between GR and MR haplotypes and stressful conditions and recurrence of MDD.

PMID- 25765758
TI  - Computer aided drug discovery of highly ligand efficient, low molecular weight
      imidazopyridine analogs as FLT3 inhibitors.
AB  - The FLT3 kinase represents an attractive target to effectively treat AML.
      Unfortunately, no FLT3 targeted therapeutic is currently approved. In line with
      our continued interests in treating kinase related disease for anti-FLT3 mutant
      activity, we utilized pioneering synthetic methodology in combination with
      computer aided drug discovery and identified low molecular weight, highly ligand
      efficient, FLT3 kinase inhibitors. Compounds were analyzed for biochemical
      inhibition, their ability to selectively inhibit cell proliferation, for FLT3
      mutant activity, and preliminary aqueous solubility. Validated hits were
      discovered that can serve as starting platforms for lead candidates. 

PMID- 25765759
TI  - Novel series of benzoquinones with high potency against 5-lipoxygenase in human
      polymorphonuclear leukocytes.
AB  - 5-Lipoxygenase (5-LO) is a potential target for pharmacological intervention with
      various inflammatory and allergic diseases. Starting from the natural dual 5
      LO/microsomal prostaglandin E2 synthase (mPGES)-1 inhibitor embelin (2,5
      dihydroxy-3-undecyl-1,4-benzoquinone, 2) that suppresses 5-LO activity in human
      primary leukocytes with IC50 = 0.8-2 MUM, we synthesized 48 systematically
      modified derivatives of 2. We modified the 1,4-quinone to 1,2-quinone, mono- or
      bimethylated the hydroxyl groups, and varied the C11-n-alkyl residue (C4- to C16
      n-alkyl or prenyl) of 2. Biological evaluation yields potent analogues being
      superior over 2 and obvious structure-activity relationships (SAR) for inhibition
      of 5-LO. Interestingly, conversion to 1,2-benzoquinone and bimethylation of the
      hydroxyl moieties strongly improves 5-LO inhibition in polymorphonuclear
      leukocytes versus 2 up to 60-fold, exemplified by the C12-n-alkyl derivative 22c
      (4,5-dimethoxy-3-dodecyl-1,2-benzoquinone) with IC50 = 29 nM. Regarding
      inhibition of mPGES-1, none of the novel benzoquinones could outperform the
      parental compound 2 (IC50 = 0.21 MUM), and only modest suppressive effects on 12-
      and 15-LOs were evident. Together, our detailed SAR study reveals 22c as highly
      potent 5-LO-selective lead compound in intact cells that warrants further
      preclinical evaluation as anti-inflammatory agent.

PMID- 25765760
TI  - High ethene/ethane selectivity in 2,2'-bipyridine-based silver(i) complexes by
      removal of coordinated solvent.
AB  - Following removal of coordinated CH3 CN, the resulting complexes [Ag(I) (2,2'
      bipyridine)][BF4 ] (1) and [Ag(I) (6,6'-dimethyl-2,2'-bipyridine)][OTf] (2) show
      ethene/ethane sorption selectivities of 390 and 340, respectively, and
      corresponding ethene sorption capacities of 2.38 and 2.18 mmol g(-1) when tested
      at an applied gas pressure of 90 kPa and a temperature of (20+/-1)  degrees C.
      These ethene/ethane selectivities are 13 times higher than those reported for
      known solid sorbents for ethene/ethane separation. For 2, ethene sorption reached
      90 % of equilibrium capacity within 15 minutes, and this equilibrium capacity was
      maintained over the three sorption/desorption cycles tested. The rates of ethene
      sorption were also measured. To our knowledge, these are the first complexes,
      designed for olefin/paraffin separations, which have open silver(I) sites. The
      high selectivities arise from these open silver(I) sites and the relatively low
      molecular surface areas of the complexes.

PMID- 25765761
TI  - Exposure to emissions from municipal solid waste incinerators and miscarriages: a
      multisite study of the MONITER Project.
AB  - BACKGROUND: Miscarriages are an important indicator of reproductive health but
      only few studies have analyzed their association with exposure to emissions from
      municipal solid waste incinerators. This study analyzed the occurrence of
      miscarriages in women aged 15-49years residing near seven incinerators of the
      Emilia-Romagna Region (Northern Italy) in the period 2002-2006. METHODS: We
      considered all pregnancies occurring in women residing during the first trimester
      of pregnancy within a 4km radius of each incinerator. Addresses were geocoded and
      exposures were characterized by a dispersion model (ADMS Urban model) producing
      pollution maps for incinerators based on PM10 stack measurements and for other
      pollution sources based on NOx ground measurements. Information on pregnancies
      and their outcomes was obtained from the Hospital Discharge Database. Simplified
      True Abortion Risks (STAR)*100 estimated pregnancies were calculated. We ran
      logistic regressions adjusting for maternal characteristics, exposure to other
      sources of pollution, and sites, considering the whole population and stratifying
      by miscarriage history. RESULTS: The study analyzed 11,875 pregnancies with 1375
      miscarriages. After adjusting for confounders, an increase of PM10 due to
      incinerator emissions was associated with an increased risk of miscarriage (test
      for trend, p=0.042). The odds ratio for the highest quartile of exposed versus
      not exposed women was 1.29, 95% CI 0.97-1.72. The effect was present only for
      women without previous miscarriages (highest quartile of exposed versus not
      exposed women 1.44, 95% CI 1.06-1.96; test for trend, p=0.009). CONCLUSION:
      Exposure to incinerator emissions is associated with an increased risk of
      miscarriage. This result should be interpreted with those of a previous study on
      reproductive health conducted in the same area that observed an association
      between incinerator exposure and preterm births.

PMID- 25765762
TI  - Assessing the human health impacts of exposure to disinfection by-products--a
      critical review of concepts and methods.
AB  - Understanding the public health implications of chemical contamination of
      drinking water is important for societies and their decision-makers. The possible
      population health impacts associated with exposure to disinfection by-products
      (DBPs) are of particular interest due to their potential carcinogenicity and
      their widespread occurrence as a result of treatments employed to control
      waterborne infectious disease. We searched the literature for studies that have
      attempted quantitatively to assess population health impacts and health risks
      associated with exposure to DBPs in drinking water. We summarised and evaluated
      these assessments in terms of their objectives, methods, treatment of
      uncertainties, and interpretation and communication of results. In total we
      identified 40 studies matching our search criteria. The vast majority of studies
      presented estimates of generic cancer and non-cancer risks based on toxicological
      data and methods that were designed with regulatory, health-protective purposes
      in mind, and therefore presented imprecise and biased estimates of health
      impacts. Many studies insufficiently addressed the numerous challenges to DBP
      risk assessment, failing to evaluate the evidence for a causal relationship, not
      appropriately addressing the complex nature of DBP occurrence as a mixture of
      chemicals, not adequately characterising exposure in space and time, not defining
      specific health outcomes, not accounting for characteristics of target
      populations, and not balancing potential risks of DBPs against the health
      benefits related with drinking water disinfection. Uncertainties were often
      poorly explained or insufficiently accounted for, and important limitations of
      data and methods frequently not discussed. Grave conceptual and methodological
      limitations in study design, as well as erroneous use of available dose-response
      data, seriously impede the extent to which many of these assessments contribute
      to understanding the public health implications of exposure to DBPs. In some
      cases, assessment results may cause unwarranted alarm among the public and
      potentially lead to poor decisions being made in sourcing, treatment, and
      provision of drinking water. We recommend that the assessment of public health
      impacts of DBPs should be viewed as a means of answering real world policy
      questions relating to drinking water quality, including microbial contaminants;
      that they should be conducted using the most appropriate and up-to-date data and
      methods, and that associated uncertainties and limitations should be accounted
      for using quantitative methods where appropriate.

PMID- 25765763
TI  - On a growth model for complex networks capable of producing power-law out-degree
      distributions with wide range exponents.
AB  - The out-degree distribution is one of the most reported topological properties to
      characterize real complex networks. This property describes the probability that
      a node in the network has a particular number of outgoing links. It has been
      found that in many real complex networks the out-degree has a behavior similar to
      a power-law distribution, therefore some network growth models have been proposed
      to approximate this behavior. This paper introduces a new growth model that
      allows to produce out-degree distributions that decay as a power-law with an
      exponent in the range from 1 to infinity. 

PMID- 25765764
TI  - LRIG1 extracellular domain: structure and function analysis.
AB  - We have expressed and purified three soluble fragments of the human LRIG1-ECD
      (extracellular domain): the LRIG1-LRR (leucine-rich repeat) domain, the LRIG1-3Ig
      (immunoglobulin-like) domain, and the LRIG1-LRR-1Ig fragment using baculovirus
      vectors in insect cells. The two LRIG1 domains crystallised so that we have been
      able to determine the three-dimensional structures at 2.3A resolution. We
      developed a three-dimensional structure for the LRIG1-ECD using homology
      modelling based on the LINGO-1 structure. The LRIG1-LRR domain and the LRIG1-LRR
      1Ig fragment are monomers in solution, whereas the LRIG1-3Ig domain appears to be
      dimeric. We could not detect any binding of the LRIG1 domains or the LRIG1-LRR
      1Ig fragment to the EGF receptor (EGFR), either in solution using biosensor
      analysis or when the EGFR was expressed on the cell surface. The FLAG-tagged
      LRIG1-LRR-1Ig fragment binds weakly to colon cancer cells regardless of the
      presence of EGFRs. Similarly, neither the soluble LRIG1-LRR nor the LRIG1-3Ig
      domains nor the full-length LRIG1 co-expressed in HEK293 cells inhibited ligand
      stimulated activation of cell-surface EGFR.

PMID- 25765765
TI  - Dissociating Indifferent, Directional, and Extreme Responding in Personality
      Data: Applying the Three-Process Model to Self- and Observer Reports.
AB  - Research suggests that respondents vary in their tendency to use the response
      scale of typical (Likert-style) questionnaires. We study the nature of the
      response process by applying a recently introduced item response theory modeling
      procedure, the three-process model, to data of self- and observer reports of
      personality traits. The three-process model captures indifferent, directional,
      and extreme responding. Substantively, we hypothesize that, and test whether,
      trait Honesty-Humility is negatively linked to extreme responding. We applied the
      three-process model to personality data of 577 dyads (self- and observer reports
      of the HEXACO Personality Inventory-Revised; Lee & Ashton, ) of Dutch and German
      undergraduate respondents. First, we provide evidence that indifferent,
      directional, and extreme responding can be separated from each other in
      personality data through the use of the three-process model. Second, we show that
      the various response processes show a pattern of correlations across traits and
      rating sources which is in line with the idea that indifferent and extreme
      responding are person-specific tendencies, whereas directional responding is
      content-specific. Third, we report findings supporting the hypothesis that
      Honesty-Humility is negatively linked to extreme responding. In Likert-based
      personality data, applying the three-process model can unveil individual
      differences in the response process.

PMID- 25765766
TI  - Clozapine therapy throughout myelosuppressive chemotherapy: regulations without
      standardization.

PMID- 25765767
TI  - Click it: do not risk it: lap seat belt causing extensive abdominal injuries.

PMID- 25765768
TI  - The role of national registries.

PMID- 25765769
TI  - Sudden cardiac death in the young: the molecular autopsy and a practical approach
      to surviving relatives.
AB  - The sudden death of a young, apparently fit and healthy person is amongst the
      most challenging scenarios in clinical medicine. Sudden cardiac death (SCD) is a
      devastating and tragic outcome of a number of underlying cardiovascular diseases.
      While coronary artery disease and acute myocardial infarction are the most common
      causes of SCD in older populations, genetic (inherited) cardiac disorders
      comprise a substantial proportion of SCD cases aged 40 years and less. This
      includes the primary arrhythmogenic disorders such as long QT syndromes and
      inherited cardiomyopathies, namely hypertrophic cardiomyopathy. In up to 30% of
      young SCD, no cause of death is identified at postmortem, so-called autopsy
      negative or sudden arrhythmic death syndrome (SADS). Management of families
      following SCD begins with a concerted effort to identify the cause of death in
      the decedent, based on either premorbid clinical details or the pathological
      findings at postmortem. Where no cause of death is identified, genetic testing of
      deoxyribonucleic acid extracted from postmortem blood (the molecular autopsy) may
      identify a cause of death in up to 30% of SADS cases. Irrespective of the genetic
      testing considerations, all families in which a sudden unexplained death has
      occurred require targeted and standardized clinical testing in an attempt to
      identify relatives who may be at-risk of having the same inherited heart disease
      and therefore also predisposed to an increased risk of SCD. Optimal care of SCD
      families therefore requires dedicated and appropriately trained staff in the
      setting of a specialized multidisciplinary cardiac genetic clinic. 

PMID- 25765770
TI  - Pantoea agglomerans - an underestimated pathogenic agent in penetrating trauma
      involving vegetative material.

PMID- 25765771
TI  - A novel cell-permeable RDP-p53 fusion protein for specific inhibition on the
      growth of cancerous neural cells.
AB  - OBJECTIVE: There is 25-35% mutation rate of p53 in cancerous neural cells and
      this rate reaches 70-76% in glioma cell line. Complement of wild-type p53 has
      become a potential strategy for protein therapy of cancerous neural cells. Here
      we investigated the feasibility of a novel RDP-p53 fusion protein for anti
      proliferation of cancerous neural cell and the possible mechanism, which would
      provide an effective approach for targeted delivery of p53 protein to treat
      cancerous neural cells. METHODS: The RDP-p53 fusion proteins are expressed in
      Escherichia coli, and they are labeled with FITC and rhodamine B by chemical
      modification. The fluorescence-labeled proteins are added to human hepatocellular
      carcinoma cells (HepG-2) and human neuroblastoma cells (SH-SY5Y) in order to
      investigate the possibility of RDP enhancing the cell uptake efficiency into
      neural cells as a cell-permeable carrier. The inhibitory effect of RDP-p53 on SH
      SY5Y and human glioma cells (U251) was evaluated by MTT assay. Moreover, the anti
      proliferation mechanism of RDP-p53 was determined by Apoptosis and Necrosis Assay
      Kit and flow cytometric analysis. RESULTS: The results showed that RDP-p53 could
      enter SH-SY5Y cells with high efficiency and selectively inhibit the growth of
      cancerous neural cells, including SH-SY5Y and U251. Also, cell apoptosis pathway
      and cell-cycle arrest at the G2/M phase were associated with the inhibition
      mechanism of RDP-p53 according to the data of flow cytometric analysis.
      CONCLUSIONS: RDP-p53 could be a novel antitumor candidate for targeting treatment
      of cancerous neural cells.

PMID- 25765772
TI  - Effect of intragastric injection of botulinum toxin A for the treatment of
      obesity: a meta-analysis and meta-regression.
AB  - BACKGROUND: Controversies persist regarding the effect of intragastric injection
      of botulinum toxin A for the treatment of obesity. OBJECTIVE: To assess the
      efficacy of intragastric botulinum toxin injection for the treatment of obesity.
      DESIGN: A systematic literature review was conducted by using the core databases.
      Pre- and posttreatment body weight data were extracted and analyzed by using
      Hedges' g. A random-effects model was applied. The methodological quality of the
      enrolled studies was assessed by the risk of bias table and Newcastle-Ottawa
      Scale. Publication bias was evaluated via the funnel plot, trim and fill method,
      Egger's test, and rank correlation test. SETTING: Meta-analysis of 8 studies.
      PATIENTS: A total of 115 patients (79 treated vs 36 placebo). INTERVENTION:
      Intragastric botulinum toxin A injection. MAIN OUTCOME MEASUREMENTS: Hedges' g,
      calculated from pre- and posttreatment body weight data and comparison of body
      weight changes between treatment and placebo group. RESULTS: The treatment group
      was associated with weight loss in a pre/post comparative approach and compared
      with the placebo group (Hedges' g: -0.443; 95% confidence interval, -0.845 to 
      0.040; P = .031; and Hedges' g: -0.521; 95% confidence interval, -0.956 to 
      0.085; P = .019). Wide area injection including the fundus or body rather than
      the antrum only was associated with weight loss. Multiple injections (>10) were
      associated with weight loss. However, a large amount of botulinum toxin A (500
      IU) was not associated with weight loss. Sensitivity analyses showed consistent
      results. Meta-regression for the botulinum toxin A dose and number of injections
      showed consistent results. Publication bias was not detected. CONCLUSION: In this
      analysis, intragastric injection of botulinum toxin A is effective for the
      treatment of obesity.

PMID- 25765774
TI  - Hemodialysis in patients over 80 years.
AB  - BACKGROUND: In Germany, every fifth patient starting dialysis is now 80 years of
      age or older. The question that is currently relevant is not whether we have to
      treat patients who are older than 80. Rather the question now is how to treat
      this elderly group of patients. METHODS: Single centre data of all dialysis
      patients aged over 80 were analyzed with regard to survival, social
      circumstances, vascular access, and pre-dialysis nephrology care. RESULTS:
      Between 2001 and 2012, 76 patients over 80 years started chronic ambulatory
      hemodialysis treatment. One-year survival was 87%, 3-year survival 52%, 5-year
      survival 27% and 10-year survival 9%. Patients (n = 55) with more than 3 months
      of nephrological care prior to dialysis (3-161 months, median 31 months) survived
      significantly longer then patients (n = 21) having had less than 3 months contact
      with nephrologists. On 31st December 2012 there were 38 patients aged >=80
      (median age 84, 80-95 years) in the chronic hemodialysis program accounting for
      19% of all dialysis patients of this center. Thirty patients (79%) had been in
      long-term nephrological care prior to dialysis initiation (3-161 months, median
      45 months). Thirty one patients (82%) started the first dialysis treatment with a
      functioning shunt access. CONCLUSION: Long-term pre-dialysis nephrology care is
      of most importance for successful dialysis treatment in the elderly, especially
      in octogenarians and nonagenarians. It enables the early establishment of
      functioning vascular access and careful scheduling of first dialysis treatment
      and increases survival. The long-term use of catheters can be avoided in almost
      all patients above the age of 80. (c) 2015 S. Karger AG, Basel.

PMID- 25765775
TI  - Safety and feasibility of Irreversible Electroporation (IRE) in patients with
      locally advanced pancreatic cancer: results of a prospective study.
AB  - PURPOSE: To evaluate the safety of the NanoKnife Low Energy Direct Current (LEDC)
      System (Irreversible Electroporation, IRE) in order to treat patients with
      unresectable pancreatic adenocarcinoma. METHODS: Prospective, nonrandomized,
      single-center clinical evaluation of ten patients with a cytohystological
      diagnosis of unresectable locally advanced pancreatic cancer (LAPC) that was no
      further responsive to standard treatments. The primary outcome was the rate of
      procedure-related abdominal complications. The secondary endpoints included the
      evaluation of the short-term efficacy of IRE through the evaluation of tumor
      reduction at imaging and biological tumor response as shown by CA 19-9, clinical
      assessments and patient quality of life. RESULTS: Ten patients (5 males, 5
      females) were enrolled, with a median age of 66 and median tumor size of 30 mm.
      All patients were treated successfully with a median procedure time of 79.5 min.
      Two procedure-related complications were described in one patient (10%): a
      pancreatic abscess with a pancreoduodenal fistula. Three patients had early
      progression of disease: one patient developed pulmonary metastases 30 days post
      IRE and two patients had liver metastases 60 days after the procedure. We
      registered an overall survival of 7.5 months (range: 2.9-15.9). CONCLUSIONS: IRE
      is a safe procedure in patients with LAPC and may represent a new technological
      option in the treatment and multimodality management of this disease.

PMID- 25765773
TI  - A simple prediction score for estimating the risk of candidaemia caused by
      fluconazole non-susceptible strains.
AB  - We aimed to develop a simple prediction score to identify fluconazole non
      susceptible (Flu-NS) candidaemia using simple clinical criteria. A derivation
      cohort was extracted from the CANDIPOP study, a prospective, multicentre,
      population-based surveillance programme on candidaemia conducted in 29 hospitals
      in Spain from April 2010 to May 2011. The score was validated with an external,
      multicentre cohort of adults with candidaemia in six tertiary hospitals in three
      countries. The prediction score was based on three variables selected by a
      logistic regression model together with the severity of disease. In total, 617
      and 297 cases of candidaemia were included in the derivation and validation
      cohorts, respectively; of these, 134 (21.7%) and 57 (19.2%) were caused by Flu-NS
      strains. Factors independently associated with Flu-NS were transplant recipient
      status (adjusted odds ratio (AOR) 2.13; 95% CI 1.01-4.55; p 0.047),
      hospitalization in a unit with a high prevalence (>= 15%) of Flu-NS strains
      (7.53; 4.68-12.10; p < 0.001), and previous azole therapy for at least 3 days
      (2.04; 1.16-3.62; p 0.014). The area under the receiver operating characteristics
      curve (AUC) was 0.76 (0.72-0.81), and using 2 points as the Flu-NS prediction
      score cut-off gave a sensitivity of 82.1%, a specificity of 65.6%, and a negative
      predictive value of 93%. The AUC in the validation cohort was 0.72 (95% CI 0.65
      0.79). Hence, the Flu-NS prediction score helped to exclude Flu-NS Candida
      strains. This could improve the selection of empirical treatments for candidaemia
      in the future.

PMID- 25765776
TI  - Short term exposure to di-n-butyl phthalate (DBP) disrupts ovarian function in
      young CD-1 mice.
AB  - Di-n-butyl phthalate (DBP) is present in many beauty and medical products. Human
      exposure estimates range from 0.007-0.01 mg/kg/day in the general population and
      up to 0.233 mg/kg/day in patients taking DBP-coated medications. Levels of
      phthalates tend to be higher in women, thus, evaluating ovarian effects of DBP
      exposure is of great importance. Mice were given corn oil (vehicle) or DBP at
      0.01, 0.1, and 1000 mg/kg/day (high dose) for 10 days to test whether DBP causes
      ovarian toxicity. Estrous cyclicity, steroidogenesis, ovarian morphology, and
      apoptosis and steroidogenesis gene expression were evaluated. DBP exposure
      decreased serum E2 at all doses, while 0.1DBP increased FSH, decreased antral
      follicle numbers, and increased mRNA encoding pro-apoptotic genes (Bax, Bad,
      Bid). Interestingly, mRNAs encoding the steroidogenic enzymes Hsd17b1, Cyp17a1
      and Cyp19a1 were increased in all DBP-treated groups. These novel findings show
      that DBP can disrupt ovarian function in mice at doses relevant to humans.

PMID- 25765777
TI  - Prenatal exposure to di-(2-ethylhexyl) phthalate (DEHP) affects reproductive
      outcomes in female mice.
AB  - This study tested the hypothesis that prenatal DEHP exposure affects female
      reproduction. To test this hypothesis, pregnant female CD-1 mice were orally
      dosed daily with tocopherol-stripped corn oil (vehicle control) or DEHP (20
      MUg/kg/day-750 mg/kg/day) from gestation day 11-birth. Pups were counted,
      weighed, and sexed at birth, ovaries were subjected to evaluations of follicle
      numbers on postnatal days (PNDs) 8 and 21, and fertility was evaluated at 3-9
      months. The results indicate that prenatal DEHP exposure increased male-to-female
      ratio compared to controls. Prenatal DEHP exposure also increased preantral
      follicle numbers at PND 21 compared to controls. Further, 22.2% of the 20
      MUg/kg/day treated animals took longer than 5 days to get pregnant at 3 months
      and 28.6% of the 750 mg/kg/day treated animals lost some of their pups at 6
      months. Thus, prenatal DEHP exposure alters F1 sex ratio, increases preantral
      follicle numbers, and causes some breeding abnormalities.

PMID- 25765778
TI  - A pilot study of selective lipopolysaccharide adsorption and coupled plasma
      filtration and adsorption in adult patients with severe sepsis.
AB  - AIM: To evaluate the safety and effectiveness of combined extracorporeal therapy
      in patients with severe sepsis after cardiac surgery. MATERIALS AND METHODS:
      Twenty patients received combined extracorporeal therapy (LPS-adsorption with
      Toraymyxin columns + CPFA). The inclusion criteria were clinical signs of severe
      sepsis, EAA = 0.6, and PCT >2 ng/ml. 20 comparable patients in the control group
      received only standard therapy. RESULTS: Each patient in the study group received
      2 daily treatments of combined extracorporeal therapy. In contrast to controls,
      we noted an increase in the values of MAP from 73 to 82 mm Hg, (p < 0.001) and
      the mean oxygenation index (from 180 to 246, p < 0.001), decrease of EAA from
      0.77 to 0.55, p < 0.001, and PCT (from 6.23 to 2.83 ng/ml, p < 0.001). The 28-day
      survival rate was 65 and 35% in the study and control groups respectively, p =
      0.11. CONCLUSION: The combined use of LPS-adsorption and CPFA in a single circuit
      with standard therapy is a safe and possibly effective adjunctive method for
      treating severe sepsis.

PMID- 25765779
TI  - Reminiscence and dementia: a therapeutic intervention.
AB  - BACKGROUND: Dementia is a significant public health problem. One non
      pharmacological therapy that has shown its effectiveness is reminiscence, which
      is a psychological intervention designed to address issues of particular
      relevance to older adults. The aim of this study was to examine the benefits of
      an integrative reminiscence program in elderly people with dementia. METHODS: A
      quasi-experimental design and purposeful sampling were conducted at two
      retirement homes. Forty-two elderly adults with dementia were studied to measure
      the effect of the therapy (23 in the experimental group and 19 in the control
      group). The treatment group activity was held in 10 sessions. RESULTS: The
      treatment group significantly improved their depressive symptoms and self
      acceptance, positive relations with others, autonomy, and environmental mastery.
      CONCLUSIONS: This study provides support for the effectiveness of integrative
      reminiscence therapy (RT) as an intervention in people with dementia, especially
      in reducing depressive symptoms and improving psychological well-being, with the
      therapy being effective on personal and emotional variables.

PMID- 25765781
TI  - Small-angle X-ray scattering: a bridge between RNA secondary structures and three
      dimensional topological structures.
AB  - Whereas the structures of small to medium-sized well folded RNA molecules often
      can be determined by either X-ray crystallography or NMR spectroscopy, obtaining
      structural information for large RNAs using experimental, computational, or
      combined approaches remains a major interest and challenge. RNA is very sensitive
      to small-angle X-ray scattering (SAXS) due to high electron density along
      phosphate-sugar backbones, whose scattering contribution dominates SAXS
      intensity. For this reason, SAXS is particularly useful in obtaining global RNA
      structural information that outlines backbone topologies and, therefore,
      molecular envelopes. Such information is extremely valuable in bridging the gap
      between the secondary structures and three-dimensional topological structures of
      RNA molecules, particularly those that have proven difficult to study using other
      structure-determination methods. Here we review published results of RNA
      topological structures derived from SAXS data or in combination with other
      experimental data, as well as details on RNA sample preparation for SAXS
      experiments. 

PMID- 25765780
TI  - Characterizing excited conformational states of RNA by NMR spectroscopy.
AB  - Conformational dynamics is a hallmark of diverse non-coding RNA functions. During
      these functional processes, RNA molecules almost ubiquitously undergo
      conformational transitions that are tuned to meet distinct structural and kinetic
      requirements for proper function. A complete mechanistic understanding of RNA
      function requires comprehensive structural and dynamic knowledge of these complex
      transitions, which often involve alternative higher-energy conformational states
      that pose a major challenge for high-resolution structural study by conventional
      methods. In this review, we describe recent progress in RNA NMR that has started
      to unveil detailed structural, thermodynamic and kinetic insights into some of
      these excited conformational states of RNA and their functional roles in biology.

PMID- 25765783
TI  - Vanadyl calix[6]arene complexes: synthesis, structural studies and ethylene homo
      (co-)polymerization capability.
AB  - Treatment of p-tert-butylcalix[6]areneH6 (L(6)H6) with in situ [LiVO(Ot-Bu)4]
      afforded, after work-up, the dark green complex
      [Li(MeCN)4][V2(O)2Li(MeCN)(L(6)H2)2].8MeCN (1.8MeCN). On one occasion, the
      reaction led to the formation of a mixture of products, the bulk of which
      differing from 1 only in the amount of solvate, viz.2.9.67MeCN. The second minor,
      yellow product has the formula {[(VO2)2(L(6)H2)(Li(MeCN)2)2].2MeCN}n (3.2MeCN),
      and comprises a 1D polymeric structure with links through the L(6)H2 ligand and
      Li2O2 units. When the reverse order of addition was employed such that lithium
      tert-butoxide (7.5 equivalents) was added to L(6)H6, and subsequently treated
      with VOCl3 (2 equiv.), the complex {[VO(THF)][VO(MU
      O)]2Li(THF)(Et2O)][L(6)]}.2Et2O.0.5THF (4.2Et2O.0.5THF), which contains a
      trinuclear motif possessing a central, octahedral vanadyl centre linked via oxo
      bridges to two tetrahedral (C3v) vanadyl centres, was isolated. The calix[6]arene
      in 4 is severely twisted and adopts a 'down, down, down, down, out, out'
      conformation. Use of excess lithium tert-butoxide led to a complex very similar
      to 4, differing only in the solvent of crystallization, namely 5.Et2O.2THF. The
      ability of 1 and 5 to act as pre-catalysts for ethylene polymerization in the
      presence of a variety of co-catalysts and under various conditions has been
      investigated. Co-polymerization of ethylene with propylene and with 1-hexene have
      also been conducted; results are compared versus VO(OEt)Cl2.

PMID- 25765782
TI  - Learning from contract change in primary care dentistry: A qualitative study of
      stakeholders in the north of England.
AB  - The aim of this research was to explore and synthesise learning from stakeholders
      (NHS dentists, commissioners and patients) approximately five years on from the
      introduction of a new NHS dental contract in England. The case study involved a
      purposive sample of stakeholders associated with a former NHS Primary Care Trust
      (PCT) in the north of England. Semi-structured interviews were conducted with 8
      commissioners of NHS dental services and 5 NHS general dental practitioners.
      Three focus group meetings were held with 14 NHS dental patients. All focus
      groups and interviews were audio recorded and transcribed verbatim. The data were
      analysed using a framework approach. Four themes were identified: 'commissioners'
      views of managing local NHS dental services'; 'the risks of commissioning for
      patient access'; 'costs, contract currency and commissioning constraints'; and
      'local decision-making and future priorities'. Commissioners reported that much
      of their time was spent managing existing contracts rather than commissioning
      services. Patients were unclear about the NHS dental charge bands and dentists
      strongly criticised the contract's target-driven approach which was centred upon
      them generating 'units of dental activity'. NHS commissioners remained relatively
      constrained in their abilities to reallocate dental resources amongst contracts.
      The national focus upon practitioners achieving their units of dental activity
      appeared to outweigh interest in the quality of dental care provided. 

PMID- 25765784
TI  - Short-term post-operative pain and discomfort following insertion of mini
      implants for retaining mandibular overdentures: a randomized controlled trial.
AB  - The retention of removable dentures by mini-implants is a relatively recent
      treatment modality and may lead to minimal post-operative trauma. This study
      compared post-operative pain and discomfort following the insertion of mini
      implants (two or four) or two standard-size implants for the retention of
      mandibular overdentures. One hundred and twenty edentulous participants (mean age
      59.5 +/- 8.5 years) were randomly allocated into three groups according to
      received treatment: (GI) four mini-implants, (GII) two mini-implants or (GIII)
      two standard implants. Seven days after implant insertion, patients answered
      questions (100-mm VAS) relating to pain, swelling, and discomfort with chewing,
      speech and hygiene, considering their experiences during the 1st and 6th day.
      Groups were compared by two-way anova (alpha = 0.05). All participants (GI: 38;
      GII: 42; GIII: 40) were analysed after 7 days. At the 6th day, GI felt
      significantly higher pain than GII and GIII. GI also reported more difficulty in
      performing oral hygiene practices than GIII during the 1st day. There was no
      significant difference between groups for the other questions and periods. No
      participant suffered unexpected side effects. The use of four mini-implants
      induces more intense post-operative pain at the 6th day than the insertion of two
      mini- or conventional fixtures, as well as more difficult oral hygiene on the 1st
      day. Clinicaltrials.gov, NCT01411683; FAPESP, 2011/00688-7 and 2011/23347-0.

PMID- 25765785
TI  - [Picture in clinical hematology no. 80].

PMID- 25765786
TI  - [Preface].

PMID- 25765787
TI  - [Overview].

PMID- 25765788
TI  - [The C5 gene polymorphism in patients with PNH].
AB  - This review is a commentary on an article entitled "Genetic variants in C5 and
      poor response to eculizumab" (N Engl J Med. 2014; 370: 632-639). The molecular
      basis for the poor response to eculizumab in Japanese patients is unclear. Of 345
      Japanese patients with paroxysmal nocturnal hemoglobinuria (PNH) who received
      eculizumab, 11 showed a poor response. All 11 had a single missense C5
      heterozygous mutation, c.2654 G>A, which predicts the polymorphism p.Arg885His.
      The prevalence of this mutation among patients with PNH (3.2%) was similar to
      that in healthy Japanese persons (3.5%). This polymorphism was also identified in
      a Han Chinese population. Non-mutant and mutant C5 both caused hemolysis in
      vitro, but only non-mutant C5 bound to and was blocked by eculizumab. In vitro
      hemolysis due to non-mutant and mutant C5 was completely blocked by N19-8, a
      monoclonal antibody that binds to a different site on C5 than does eculizumab.
      The functional capacity of the C5 polymorphism p.Arg885His, together with its
      failure to undergo blockade by eculizumab, accounts for the poor response to this
      agent in patients who carry this mutation. 

PMID- 25765789
TI  - [Epigenetic dysregulation in myelodysplastic syndrome].
AB  - Myelodysplastic syndrome (MDS) is a clonal hematopoietic stem cell disease
      characterized by impaired hematopoiesis and an increased risk of transformation
      to acute myeloid leukemia. Various epigenetic regulators are mutated in MDS
      patients, indicating that accumulation of epigenetic alterations together with
      genetic alterations plays a crucial role in the development of MDS. 

PMID- 25765790
TI  - [Update on the biology of heme synthesis in erythroid cells].
AB  - Heme is a prosthetic group of hemoproteins playing important roles in oxygen
      transport, detoxification, circadian rhythm, microRNA processing, regulation of
      transcription, and translation. The majority of heme (-85%) is synthesized in red
      blood cells mainly for hemoglobin production, whereas hepatocytes account for
      most of the rest, functioning primarily in the synthesis of cytochrome P450
      enzymes and mitochondrial respiratory enzymes. Thus, failure of heme biosynthesis
      causes severe inherited or acquired disorders in humans, including porphyria and
      sideroblastic anemia. The heme biosynthetic pathway is composed of eight enzymes
      that work in either mitochondria or the cytoplasm, which have been extensively
      researched and frequently reviewed. On the other hand, the mechanisms governing
      transport and intracellular trafficking of heme intermediates, as well as their
      potential links to human diseases, are poorly understood. Herein, we focus on
      recent understanding of the heme biosynthetic pathway and on human disorders due
      to defective heme synthesis in erythroid cells, such as X-linked sideroblastic
      anemia and erythropoietic protoporphyria. 

PMID- 25765791
TI  - [Overview].

PMID- 25765792
TI  - [Progress in molecularly targeted therapies for acute myeloid leukemia].
AB  - Genetic abnormalities including specific point mutations have recently been
      confirmed by applying comprehensive genome sequencing analyses. Molecular
      targeting therapies, which focus on the mutated proteins and over-expressed
      proteins in acute myeloid leukemia (AML) cells, are now being developed in
      clinical studies and/or based on in vitro analyses. This manuscript summarizes
      the genetic abnormalities in AML cells and some of the current molecular
      targeting therapies including FLT3 inhibitors (e.g. AC220; Quizartinib), Polo
      like kinase 1 (PLK1) inhibitors (e.g. BI-6727; Volasertib), IDH2 inhibitors (e.g.
      AG-221), and XPO1 inhibitors (e.g. KPT-330; Selinexor). 

PMID- 25765793
TI  - [Molecular mechanisms in the resistance of CML stem cells to tyrosine kinase
      inhibitors and novel targets for achieving a cure].
AB  - Tyrosine kinase inhibitors (TKIs) have dramatically improved the clinical
      outcomes of patients with chronic myeloid leukemia (CML) in the chronic phase.
      However, even if these patients achieve and maintain marked molecular responses
      such as a complete molecular response (BCR-ABL/ABL<=0.032% by international
      scale), discontinuation of TKI treatment results in early molecular relapse in
      most cases. Although several factors such as the Sokal score and the duration of
      TKI treatment have been identified as being related to treatment-free remission
      (TFR), identification of more definite factors or clinical conditions that would
      enable us to select patients who can maintain TFR is required. Relapse after TKI
      discontinuation is considered to be attributable to CML stem cells surviving even
      in patients who maintain marked molecular responses. A number of in vitro
      experiments have shown that TKI by itself cannot kill CML stem cells. Also, CML
      stem cells are resistant to TKI in a manner dependent on self-renewal factors
      (Hh, Wnt/beta-catenin), cell cycle regulators (PML), metabotropic factors (FOXO3,
      Alox5), and adhesion molecules (CXCR4). In addition, surface markers specific for
      CML stem cells such as IL-1RAP and CD26 have been identified. New therapeutic
      strategies targeting these molecules in combination with TKI hold promise of
      achieving a more effective strategy for curing CML. 

PMID- 25765794
TI  - [Molecularly pathogenesis and molecular targeted therapy for myeloproliferative
      neoplasms].
AB  - Activation of the JAK-STAT pathway by driver mutations of JAK2, CALR or MPL is
      the pathogenesis of myeloproliferative neoplasms (MPN). Mutations in epigenetic
      regulators that often coexist with driver mutations reinforce the function of MPN
      initiating cells and support MPN onset and maintenance. In myelofibrosis
      patients, JAK2 inhibitors exerted an innovative therapeutic effect on
      splenomegaly and constitutional symptoms, but had minimal effects on the
      JAK2V617F allele burden. Epigenetic abnormalities may be a good target for novel
      therapeutic strategies aiming to induce molecular remission in myelofibrosis
      patients. New information obtained by next-generation sequencing technologies
      would greatly contribute to elucidation of the mechanisms underlying MPN onset,
      progression and leukemic transformation. 

PMID- 25765795
TI  - [Overview].

PMID- 25765796
TI  - [Acquired coagulant factor inhibitors].
AB  - Acquired coagulation factor inhibitors are an autoimmune disease causing bleeding
      symptoms due to decreases in the corresponding factor (s) which result from the
      appearance of autoantibodies against coagulation factors (inhibitor). This
      disease is quite different from congenital coagulation factor deficiencies based
      on genetic abnormalities. In recent years, cases with this disease have been
      increasing, and most have anti-factor VIII autoantibodies. The breakdown of the
      immune control mechanism is speculated to cause this disease since it is common
      in the elderly, but the pathology and pathogenesis are presently unclear. We
      herein describe the pathology and pathogenesis of factor VIII and factor V
      inhibitors. Characterization of these inhibitors leads to further analysis of the
      coagulation process and the activation mechanisms of clotting factors. In the
      future, with the development of new clotting examination method (s), we
      anticipate that further novel findings will be obtained in this field through
      inhibitor analysis. In addition, detailed elucidation of the coagulation
      inhibitory mechanism possibly leading to hemostatic treatment strategies for
      acquired coagulation factor disorders will be developed.

PMID- 25765797
TI  - [Progress in diagnosis and treatment for disseminated intravascular coagulation].
AB  - As the development of a hypercoagulable state in the setting of disseminated
      intravascular coagulation (DIC) induces localized infection, therapy for DIC
      should be evaluated according to the findings of examinations for both severe
      sepsis and DIC. DIC is classified into the following types: "bleeding type,"
      "organ failure type," "asymptomatic type," and "complication type." The "bleeding
      type" and "organ failure type" are considered to reflect the "plasmin inhibitor
      (PI) deficiency type" and "antithrombin (AT) deficiency type," respectively. In
      order to improve the diagnosis of DIC, in particular limitations in global
      coagulation tests, the Japanese Society of Thrombosis and Hemostasis recently
      proposed tentative diagnostic criteria for DIC using hemostatic molecular markers
      and AT. The recommendations for treatment of DIC, especially the use of AT
      concentrates, recombinant activated protein C and thrombomodulin, vary among
      several guidelines for the management of DIC. These agents inhibit the effects of
      key proteases in activating coagulation and consequently exert an anti
      inflammatory effect on DIC. Hence, it is necessary to extensively evaluate these
      agents in well-conducted clinical trials. 

PMID- 25765798
TI  - [Recent advances in pathophysiology and treatment of immune thrombocytopenia].
AB  - Immune thrombocytopenia (ITP) is an autoimmune disorder characterized by isolated
      thrombocytopenia caused by immune-mediated platelet destruction and impairment of
      platelet production. Recent studies have uncovered details involving the target
      regions of platelet-associated anti-GPIIb/IIIa antibodies, pathological
      differences depending on the specificity of target antigens, and cellular
      abnormalities, especially impairment of regulatory T cells contributing to the
      pathogenesis of ITP. Treatment of ITP has been changed dramatically by the
      application of thrombopoietin receptor agonists, TPO-RAs, in patients
      unresponsive to traditional steroids and splenectomy. Rituximab has also been
      used in Western countries for ITP patients and its long-term efficacy has become
      increasingly clear. Clinical problems awaiting solution in ITP management include
      improving the efficacy of treatments for newly-diagnosed ITP, confirmation of the
      long-term efficacy and safety of TPO-RAs, and determination of the positioning of
      rituximab in the treatment sequence of ITP. 

PMID- 25765799
TI  - [Atypical HUS caused by complement-related abnormalities].
AB  - Atypical hemolytic uremic syndrome (aHUS) is a rare disease characterized by the
      triad of microangiopathic hemolytic anemia, thrombocytopenia, and acute renal
      failure. The term aHUS was historically used to distinguish this disorder from
      Shiga-toxin producing Escherichia coli (STEC)-HUS. Many aHUS cases (approximately
      70%) are reportedly caused by uncontrolled complement activation due to genetic
      mutations in the alternative pathway, including complement factor H (CFH),
      complement factor I (CFI), membrane cofactor protein (MCP), thrombomodulin
      (THBD), complement component C3 (C3), and complement factor B (CFB). Mutations in
      the coagulation pathway, such as diacylglycerol kinase epsilon (DGKE) and
      plasminogen, are also reported to be causes of aHUS. In this review, we have
      focused on aHUS due to complement dysfunction. aHUS is suspected based on plasma
      ADAMTS13 activity of 10% or more, and being negative for STEC-HUS, in addition to
      the aforementioned triad. Complement genetic studies provide a more specific
      diagnosis of aHUS. Plasma therapy is the first-line treatment for patients with
      aHUS and should be initiated as soon as the diagnosis is suspected. Recently,
      eculizumab, a humanized monoclonal antibody against C5, was shown to be an
      effective treatment for aHUS. Therefore, early diagnosis and identification of
      the underlying pathogenic mechanism is important for improving the outcome of
      aHUS. 

PMID- 25765800
TI  - [Two novel potential markers for iron metabolism: hepcidin and non-transferrin
      bound iron (NTBI)].
AB  - Iron is an essential metal for all living organisms. For example, iron is used in
      hemoglobin synthesis. However, iron overload can cause serious organ damage.
      Therefore, iron balance is tightly regulated while iron dynamically moves
      throughout the body, including the gastrointestinal tract, bone marrow, blood,
      liver, and spleen. Iron balance occasionally collapses, allowing either iron
      deficiency or iron overload to occur. Various laboratory tests and serum markers
      are now available for evaluating such iron dysregulation. The hepatic iron
      concentration, as determined by liver biopsy, and serum ferritin are both quite
      informative. In addition, certain novel markers and modalities are becoming
      available due to remarkable progress made in recent research on iron metabolism.
      In this review, the iron regulatory peptide-hormone hepcidin and non-transferrin
      bound iron (NTBI) are introduced as novel potential biomarkers for iron
      metabolism. 

PMID- 25765801
TI  - [Alleviated anemia by bendamustine in cold agglutinin disease associated with
      small lymphocytic lymphoma].
AB  - A 77-year-old man was diagnosed with cold agglutinin disease in 2004. He had been
      treated with prednisolone with stabilization of hemoglobin in the 6- to 8-g/dl
      range. However, his hemolytic anemia worsened, and computed tomography showed
      systemic lymphadenopathy in May 2012. A pathological diagnosis of small
      lymphocytic lymphoma was made based on an inguinal lymph node biopsy. Treatment
      was started with rituximab. However, there was no response to 6 doses of
      rituximab monotherapy. He next received 6 courses of bendamustine in combination
      with rituximab. This resulted in stabilization of hemoglobin and independence
      from transfusion support. To the best of our knowledge, this is only the second
      case report describing bendamustine plus rituximab treatment for non-Hodgkin
      lymphoma complicated by cold agglutinin disease. Our results in this case suggest
      bendamustine to potentially be a useful therapeutic option in patients with cold
      agglutinin disease. 

PMID- 25765802
TI  - [Adult T cell leukemia-lymphoma with allo-HSCT after treatment for pulmonary
      involvement with Mogamulizumab].
AB  - Adult T cell lymphoma-leukemia (ATL) is a highly aggressive disease and
      allogeneic hematopoietic transplantation (allo-HSCT) is the only therapeutic
      option for achieving a cure. However, some ATL patients cannot undergo HSCT. One
      of the important reasons for restricting HSCT in ATL is the high incidence of
      pulmonary complications associated with ATL including opportunistic infections,
      infiltration of ATL cells, and HTLV-1 associated bronchopneumonopathy. Herein, we
      report an ATL case with pulmonary infiltration of ATL cells successfully treated
      with allo-HSCT after improvement of pulmonary function with administration of the
      anti-CCR4 antibody mogamulizumab. To our knowledge, this is the first ATL case
      showing improvement of pulmonary invasion of ATL cells after treatment with
      mogamulizumab. In addition, this case suggests that mogamulizumab treatment might
      be useful as a bridge to allo-HSCT in ATL patients. 

PMID- 25765803
TI  - [Treatment-free molecular remission achieved by combination therapy with imatinib
      and IFNalpha in CML with BIM deletion polymorphism relapsed after stop imatinib].
AB  - A 51-year-old man with chronic myeloid leukemia (CML) was treated with imatinib
      (IM). After 24 months of treatment, he achieved a complete molecular response
      (CMR), which he sustained for 3 years. However, 4 months after discontinuing IM
      treatment, the CML relapsed. The patient was treated again with IM and achieved
      CMR. A combination of IM and interferon-alpha (IFNalpha) was administered for the
      following year, and then discontinued. The patient has since sustained CMR
      without therapy for 24 months, to date. This patient was found to have a BCL2L11
      (BIM) deletion polymorphism. CML patients with a BIM deletion polymorphism show a
      low response to IM, and we infer that the BIM deletion polymorphism is a negative
      factor for discontinuation of IM. IFNalpha treatment is expected to prevent
      relapse during immunological surveillance. Therefore, the combination of IM and
      IFNalpha might be a feasible approach for CML patients who experience difficulty
      with IM discontinuation. 

PMID- 25765804
TI  - [Successful treatment with rituximab for type III cryoglobulinemia].
AB  - A 71-year-old man with rheumatoid arthritis was referred to our hospital with
      complaints of face and leg edema and was admitted for management of acute renal
      failure. Type III cryoglobulinemia was diagnosed based on histopathological
      findings of a kidney biopsy which revealed cryoglobulinemic nephropathy.
      Immunofixation showed no serum M-proteins. Steroid pulse and apheresis were
      initiated but the proteinuria did not improve. Rituximab was administered four
      times weekly as a second-line treatment, eliminating the proteinuria, after which
      the steroid dose was gradually tapered until discontinuation. No recurrence of
      proteinuria was observed more than 1 year after termination of rituximab therapy.
      This suggests that rituximab exerts a long-term effect. Although this patient
      developed candidiasis during rituximab therapy, the therapy could be continued as
      the antifungal agents prevented exacerbation of the infection. Rituximab can be
      used for the treatment of steroid-refractory cryoglobulinemia. However,
      clinicians should remain aware of possible infections associated with
      immunosuppression.

PMID- 25765806
TI  - Late-onset epileptic spasms in a female patient with a CASK mutation.
AB  - We report a female patient with late-onset epileptic spasms (ESs) of a rare form,
      distinct from those seen in typical West syndrome, in association with a
      heterozygous frameshift CASK mutation (c.1896dupC (p.C633fs(*)2)). She has a
      phenotype of microcephaly with pontine and cerebellar hypoplasia (MICPCH), and
      has had intractable ESs in clusters since 3 years 8 months of age with
      multifocal, particularly bifrontal, epileptic discharges in electroencephalogram.
      The available literature on patients with both ESs and CASK mutations has been
      reviewed, revealing that four of the five female children, including the present
      girl, had late-onset ESs, in contrast to the four males, who tended toward early
      onset ESs.

PMID- 25765808
TI  - Re: A validation study on the use of intra-operative video recording as an
      objective assessment tool for core ENT surgery.

PMID- 25765809
TI  - Re: Transnasal oesophagoscopy: diagnostic and management outcomes in a
      prospective cohort of 257 consecutive cases and practice implications.

PMID- 25765810
TI  - Hospital stay following complex major head and neck resection: what factors play
      a role?

PMID- 25765811
TI  - A helpful technique for manual stability and avoiding fatigue during
      microlaryngoscopy.

PMID- 25765812
TI  - Task Shifting and Skin Punch for the Histologic Diagnosis of Kaposi's Sarcoma in
      Sub-Saharan Africa: A Public Health Solution to a Public Health Problem.
AB  - Fueled by HIV, sub-Saharan Africa has the highest incidence of Kaposi's sarcoma
      (KS) in the world. Despite this, KS diagnosis in the region is based mostly on
      clinical grounds. Where biopsy is available, it has traditionally been excisional
      and performed by surgeons, resulting in multiple appointments, follow-up visits
      for suture removal, and substantial costs. We hypothesized that a simpler
      approach - skin punch biopsy - would make histologic diagnosis more accessible.
      To address this, we provided training and equipment for skin punch biopsy of
      suspected KS to three HIV clinics in East Africa. The procedure consisted of
      local anesthesia followed by a disposable cylindrical punch blade to obtain
      specimens. Hemostasis is facilitated by Gelfoam(r). Patients removed the dressing
      after 4 days. From 2007 to 2013, 2,799 biopsies were performed. Although
      originally targeted to be used by physicians, biopsies were performed
      predominantly by nurses (62%), followed by physicians (15%), clinical officers
      (12%) and technicians (11%). There were no reports of recurrent bleeding or
      infection. After minimal training and provision of inexpensive equipment (USD
      3.06 per biopsy), HIV clinics in East Africa can integrate same-day skin punch
      biopsy for suspected KS. Task shifting from physician to non-physician greatly
      increases access. Skin punch biopsy should be part of any HIV clinic's essential
      procedures. This example of task shifting may also be applicable to the diagnosis
      of other cancers (e.g., breast) in resource-limited settings.

PMID- 25765813
TI  - Involvement of microsomal NADPH-cytochrome P450 reductase in metabolic reduction
      of drug ketones.
AB  - Recently, it was found that the carbonyl group of 1-[3-(4-phenoxyphenoxy)-2
      oxopropyl]indole-5-carboxylic acid (5), an inhibitor of the pro-inflammatory
      enzyme cytosolic phospholipase A2 alpha, is easily reduced by rat liver S9
      fractions in vitro. Determination of the inhibitory potency of certain putative
      inhibitors of carbonyl reducing enzymes on the transformation of the ketone
      derivative 5 to its alcohol 6 by recombinant microsomal NADPH-cytochrome P450
      reductase and by recombinant cytosolic carbonyl reductase-1 now reveals that
      these compounds show a lack of specificity for these two enzymes in part. Thus,
      an assignment of the roles of different carbonyl reductases in metabolic keto
      reduction by the use of inhibitors is problematic. In addition, the ability of
      NADPH-cytochrome P450 reductase and carbonyl reductase-1 to reduce the ketone
      groups of the drugs haloperidol and daunorubicin was examined. Under the
      conditions applied, a pronounced reductive metabolism was only observed for
      daunorubicin in the presence of microsomal NADPH-cytochrome P450 reductase.
      Similarly, in rat liver S9 fractions a marked reduction of daunorubicin was seen,
      while haloperidol was only slightly metabolized to its alcohol. After separation
      of the S9 homogenate into a microsomal and a cytosolic fraction, it became
      evident that the ketone groups of daunorubicin, haloperidol and compound 5 were
      mainly reduced by cytosolic enzymes. However, since microsomes also catalysed
      these carbonyl reductions to some extent, it can be concluded that microsomal
      NADPH-cytochrome P450 reductase can contribute to metabolic keto reductions in
      xenobiotics. Copyright (c) 2015 John Wiley & Sons, Ltd.

PMID- 25765815
TI  - Understanding forearm fractures in young children: Abuse or not abuse?
AB  - This retrospective study describes the characteristics and mechanisms of forearm
      fractures in children <18 months adding to the evidence-base about forearm
      fractures. It also examines which features of forearm fractures in young children
      may help discriminate between abusive and noninflicted injuries. Electronic
      medical records were reviewed for eligible patients evaluated between September
      1, 2007 and January 1, 2012 at two children's hospitals in Chicago, IL. The main
      outcome measures were the type of fracture and the etiology of the fracture
      (abuse versus not abuse). The 135 included patients sustained 216 forearm
      fractures. Most were buckle (57%) or transverse (26%). Child protection teams
      evaluated 47 (35%) of the patients and diagnosed 11 (23%) as having fractures
      caused by abuse. Children with abusive versus non-inflicted injuries had
      significant differences in age (median age 7 versus 12 months), race, and
      presence of additional injuries. Children with abusive forearm fractures often
      presented without an explanation or a changing history for the injury. Children
      with non-inflicted forearm fractures often presented after a fall. No particular
      type of forearm fracture was specific for child abuse. Any forearm fracture in a
      young child should be evaluated with special attention to the details of the
      history and the presence of other injuries. Young age, additional injuries, and
      an absent or inconsistent explanation should increase concern that the fracture
      was caused by child abuse. 

PMID- 25765814
TI  - Transcriptome analysis of Panax vietnamensis var. fuscidicus discovers putative
      ocotillol-type ginsenosides biosynthesis genes and genetic markers.
AB  - BACKGROUND: P. vietnamensis var. fuscidiscus, called "Yesanqi" in Chinese, is a
      new variety of P. vietnamensis, which was first found in Jinping County, the
      southern part of Yunnan Province, China. Compared with other Panax plants, this
      species contains higher content of ocotillol-type saponin, majonoside R2. Despite
      the pharmacological importance of ocotillol-type saponins, little is known about
      their biosynthesis in plants. Hence, P. vietnamensis var. fuscidiscus is a
      suitable medicinal herbal plant species to study biosynthesis of ocotillol-type
      saponins. In addition, the available genomic information of this important herbal
      plant is lacking. RESULTS: To investigate the P. vietnamensis var. fuscidiscus
      transcriptome, Illumina HiSeqTM 2000 sequencing platform was employed. We
      produced 114,703,210 clean reads, assembled into 126,758 unigenes, with an
      average length of 1,304 bp and N50 of 2,108 bp. Among these 126,758 unigenes,
      85,214 unigenes (67.23%) were annotated based on the information available from
      the public databases. The transcripts encoding the known enzymes involved in
      triterpenoid saponins biosynthesis were identified in our Illumina dataset. A
      full-length cDNA of three Squalene epoxidase (SE) genes were obtained using
      reverse transcription PCR (RT-PCR) and the expression patterns of ten unigenes
      were analyzed by reverse transcription quantitative real-time PCR (RT-qPCR).
      Furthermore, 15 candidate cytochrome P450 genes and 17 candidate UDP
      glycosyltransferase genes most likely to involve in triterpenoid saponins
      biosynthesis pathway were discovered from transcriptome sequencing of P.
      vietnamensis var. fuscidiscus. We further analyzed the data and found 21,320
      simple sequence repeats (SSRs), 30 primer pairs for SSRs were randomly selected
      for validation of the amplification and polymorphism in 13 P. vietnamensis var.
      fuscidiscus accessions. Meanwhile, five major triterpene saponins in roots of P.
      vietnamensis var. fuscidicus were determined using high performance liquid
      chromatography (HPLC) and evaporative light scattering detector (ELSD).
      CONCLUSIONS: The genomic resources generated from P. vietnamensis var.
      fuscidiscus provide new insights into the identification of putative genes
      involved in triterpenoid saponins biosynthesis pathway. This will facilitate our
      understanding of the biosynthesis of triterpenoid saponins at molecular level.
      The SSR markers identified and developed in this study show genetic diversity for
      this important crop and will contribute to marker-assisted breeding for P.
      vietnamensis var. fuscidiscus.

PMID- 25765816
TI  - "Someone will notice, and someone will care": How to build Strong Communities for
      Children.
AB  - Derived from the recommendations of the U.S. Advisory Board on Child Abuse and
      Neglect, Strong Communities for Children is a universal community-wide approach
      to prevention of child maltreatment. It is intended to change community norms-to
      facilitate informal support for families and to strengthen parents' belief that
      they can improve the quality of life for their own and their neighbors' families.
      A phased intervention, Strong Communities begins with recruitment and
      mobilization of volunteers, initially to spread Strong Communities' messages and
      ultimately to provide direct assistance to families of young children. Principle
      driven, Strong Communities uses assets in the community to expand and strengthen
      networks of supportive relationships and, in particular, to increase support to
      parents. At least in concept, Strong Communities appears to be applicable in
      highly disparate communities and societies.

PMID- 25765817
TI  - Shape-dependent adhesion and friction of Au nanoparticles probed with atomic
      force microscopy.
AB  - The relation between surface structure and friction and adhesion is a long
      standing question in tribology. Tuning the surface structure of the exposed
      facets of metal nanoparticles is enabled by shape control. We investigated the
      effect of the shape of Au nanoparticles on friction and adhesion. Two
      nanoparticle systems, cubic nanoparticles with a low-index (100) surface and
      hexoctahedral nanoparticles with a high-index (321) surface, were used as model
      nanoparticle surfaces. Atomic force microscopy was used to probe the nanoscale
      friction and adhesion on the nanoparticle surface. Before removing the capping
      layers, the friction results include contributions from both the geometric factor
      and the presence of capping layers. After removing the capping layers, we can see
      the exclusive effect of the surface atomic structure while the geometric effect
      is maintained. We found that after removing the capping layer, the cubic Au
      nanoparticles exhibited higher adhesion and friction, compared with cubes capped
      with layers covering 25% and 70%, respectively. On the other hand, the adhesion
      and friction of hexoctahedral Au nanoparticles decreased after removing the
      capping layers, compared with nanoparticles with capping layers. The difference
      in adhesion and friction forces between the bare Au surfaces and Au nanoparticles
      with capping layers cannot be explained by geometric factors, such as the slope
      of the nanoparticle surfaces. The higher adhesion and friction forces on cubic
      nanoparticles after removing the capping layers is associated with the atomic
      structure of (100) and (321) (i.e., the flat (100) surfaces of the cubic
      nanoparticles have a larger contact area, compared with the rough (321) surfaces
      of the hexoctahedral nanoparticles). This study implies an intrinsic relation
      between atomic structure and nanomechanical properties, with potential
      applications for controlling nanoscale friction and adhesion via colloid
      chemistry. 

PMID- 25765818
TI  - Cost savings of human milk as a strategy to reduce the incidence of necrotizing
      enterocolitis in very low birth weight infants.
AB  - BACKGROUND: Necrotizing enterocolitis (NEC) is a costly morbidity in very low
      birth weight (VLBW; <1,500 g birth weight) infants that increases hospital length
      of stay and requires expensive treatments. OBJECTIVES: To evaluate the cost of
      NEC as a function of dose and exposure period of human milk (HM) feedings
      received by VLBW infants during the neonatal intensive care unit (NICU)
      hospitalization and determine the drivers of differences in NICU hospitalization
      costs for infants with and without NEC. METHODS: This study included 291 VLBW
      infants enrolled in an NIH-funded prospective observational cohort study between
      February 2008 and July 2012. We examined the incidence of NEC, NICU
      hospitalization cost, and cost of individual resources used during the NICU
      hospitalization. RESULTS: Twenty-nine (10.0%) infants developed NEC. The average
      total NICU hospitalization cost (in 2012 USD) was USD 180,163 for infants with
      NEC and USD 134,494 for infants without NEC (p = 0.024). NEC was associated with
      a marginal increase in costs of USD 43,818, after controlling for demographic
      characteristics, risk of NEC, and average daily dose of HM during days 1-14 (p <
      0.001). Each additional ml/kg/day of HM during days 1-14 decreased non-NEC
      related NICU costs by USD 534 (p < 0.001). CONCLUSIONS: Avoidance of formula and
      use of exclusive HM feedings during the first 14 days of life is an effective
      strategy to reduce the risk of NEC and resulting NICU costs in VLBW infants.
      Hospitals investing in initiatives to feed exclusive HM during the first 14 days
      of life could substantially reduce NEC-related NICU hospitalization costs.

PMID- 25765820
TI  - Chronic disease and aging: screening and management applications.

PMID- 25765819
TI  - A2b adenosine signaling represses CIITA transcription via an epigenetic mechanism
      in vascular smooth muscle cells.
AB  - Chronic inflammation plays a major role in the pathogenesis of atherosclerosis.
      Vascular smooth muscle cells (VSMC), by expressing and presenting major
      histocompatibility complex II (MHC II) molecules, help recruit T lymphocyte and
      initiate the inflammatory response within the vasculature. We have previously
      shown that VSMCs isolated from mice with deficient adenosine A2b receptor (A2b
      null) exhibit higher expression of class II transactivator (CIITA), the master
      regulator of MHC II transcription, compared to wild type littermates. Here we
      report that activation of A2b adenosine signaling suppresses CIITA expression in
      human aortic smooth muscle cells. Down-regulation of CIITA expression was largely
      attributable to transcriptional repression of type III and IV promoters.
      Chromatin immunoprecipitation (ChIP) analyses revealed that A2b signaling
      repressed CIITA transcription by attenuating specific histone modifications on
      the CIITA promoters in a STAT1-dependent manner. STAT1 interacted with PCAF/GCN5,
      histone H3K9 acetyltransferases, and WDR5, a key component of the mammalian H3K4
      methyltransferase complex, to activate CIITA transcription. A2b signaling
      prevented recruitment of PCAF/GCN5 and WDR5 to the CIITA promoters in a STAT1
      dependent manner. In conclusion, our data suggest that adenosine A2b signaling
      represses CIITA transcription in VSMCs by manipulating the interaction between
      STAT1 and the epigenetic machinery. 

PMID- 25765821
TI  - Developing and testing a decision aid for use by providers in making
      recommendations: about mammography screening in older women.
AB  - Breast cancer incidence increases with age, but many older women do not receive
      appropriate mammography screening. A tool to support provider decision making
      holds potential to help providers and patients reach the best-informed decisions
      possible. We developed and tested a decision aid (DA) for healthcare providers to
      use in mammography screening recommendations in older women. Literature review,
      expert opinion, focus groups, and pilot testing of the DA were conducted in a
      university ambulatory geriatrics practice. Provider evaluations of the DA after
      piloting were collected and analyzed. Geriatricians reported important factors in
      decision making included patient life-expectancy, preferences, cognitive
      function, and individualization. Geriatricians reported the DA would have helped
      them make recommendations for mammography screening in 66% of pilot cases. It was
      less helpful when there was more certainty regarding decision making. 

PMID- 25765822
TI  - Perceived benefits, motives, and barriers to aqua-based exercise among older
      adults with and without osteoarthritis.
AB  - This study aimed to (a) identify factors that motivate older adults to
      participate in aqua-based exercise; (b) identify potential barriers; and (c)
      compare perceptions between older adults with and without osteoarthritis (OA).
      Fifteen adults above 60 years of age participated in one of three focus groups
      during which they discussed perceived benefits, motives, and barriers to aqua
      exercise. Pain reduction was considered a major benefit among those with OA,
      improved health and fitness was a principal benefit for those without OA. All
      participants felt that the instructor could act as both a motivator and barrier;
      the most significant barrier was cold changing facilities in winter. With the
      exception of pain reduction, perceived benefits, motivators, and barriers to aqua
      based exercise are similar among older adults with and without OA. A greater
      understanding of these factors may help us to facilitate older adults with OA to
      initiate and adhere to aqua-based exercise. 

PMID- 25765823
TI  - The Effects of EnhanceFitness (EF) training on dual-task walking in older adults.
AB  - Decline in dual-task walking performance is associated with increased risk of
      falls among older adults. The objective of this study is to determine whether 18
      hr of participation in EnhanceFitness (EF), an evidence-based group exercise
      program, improves dual-task walking performance among community-dwelling older
      adults. Twenty-eight healthy, community-dwelling older adults were evaluated
      before participating in EF and after 18 hr of participation. Gait speed was
      evaluated under single task and dual tasks using the TUG (Timed Up and Go) and 1
      min walk tests. Dual-task costs (DTC), the relative cost of dual-task performance
      compared to single-task performance, were calculated for both cognitive and motor
      tasks. Postural control and executive functions were evaluated as well. After 18
      hr of EF, dual-task walking performance improved. Single-task performance
      improved as well as postural control and executive function. There was no
      significant change in DTC across all measurements, except for the cognitive task
      of the TUG. 

PMID- 25765824
TI  - Older drivers' reasons for reducing the overall amount of their driving and for
      avoiding selected driving situations.
AB  - Structured telephone interviews were conducted with 840 older drivers to explore
      their reasons for self-regulating their driving. The main reason for reduced
      driving was having fewer activities to drive to, and for avoidance of driving
      situations, reasons also included not liking or feeling insecure about driving in
      the situation. The lower-functioning participants, but still only a minority,
      were more likely to indicate decline in vision and reaction time as reasons for
      avoidance. Women were more likely to indicate lack of confidence as a reason for
      avoidance. The results suggest that the reduction in driving and avoidance of
      driving situations are separate types of self-regulatory behavior; that self
      regulation of driving is an automatic process, in which older drivers are not
      aware that they are compensating for functional loss; and that it is important to
      acknowledge gender differences when designing interventions aimed at enhancing
      safe mobility. 

PMID- 25765825
TI  - Luminescent nitridophosphates CaP2 N4 :Eu(2+) , SrP2 N4 :Eu(2+) , BaP2 N4 :Eu(2+)
      , and BaSr2 P6 N12 :Eu(2.).
AB  - Nitridophosphates MP2 N4 :Eu(2+) (M=Ca, Sr, Ba) and BaSr2 P6 N12 :Eu(2+) have
      been synthesized at elevated pressures and 1100-1300  degrees C starting from the
      corresponding azides and P3 N5 with EuCl2 as dopant. Addition of NH4 Cl as
      mineralizer allowed for the growth of single crystals. This led to the successful
      structure elucidation of a highly condensed nitridophosphate from single-crystal
      X-ray diffraction data (CaP2 N4 :Eu(2+) (P63 , no. 173), a=16.847(2),
      c=7.8592(16) A, V=1931.7(6) A(3) , Z=24, 2033 observed reflections, 176 refined
      parameters, wR2 =0.096). Upon excitation by UV light, luminescence due to parity
      allowed 4f(6) ((7) F)5d(1) ->4f(7) ((8) S7/2 ) transition was observed in the
      orange (CaP2 N4 :Eu(2+) , lambdamax =575 nm), green (SrP2 N4 :Eu(2+) , lambdamax
      =529 nm), and blue regions of the visible spectrum (BaSr2 P6 N12 :Eu(2+) and BaP2
      N4 :Eu(2+) , lambdamax =450 and 460 nm, respectively). Thus, the emission
      wavelength decreases with increasing ionic radius of the alkaline-earth ions. The
      corresponding full width at half maximum values (2240-2460 cm(-1) ) are
      comparable to those of other known Eu(2+) -doped (oxo)nitrides emitting in the
      same region of the visible spectrum. Following recently described quaternary Ba3
      P5 N10 Br:Eu(2+) , this investigation represents the first report on the
      luminescence of Eu(2+) -doped ternary nitridophosphates. Similarly to
      nitridosilicates and related oxonitrides, Eu(2+) -doped nitridophosphates may
      have the potential to be further developed into efficient light-emitting diode
      phosphors.

PMID- 25765826
TI  - Interaction between lichen secondary metabolites and antibiotics against clinical
      isolates methicillin-resistant Staphylococcus aureus strains.
AB  - The in vitro antimicrobial activities of five compounds isolated from lichens,
      collected in several Southern regions of Chile (including the Chilean Antarctic
      Territory), were evaluated alone and in combination with five therapeutically
      available antibiotics, using checkerboard microdilution assay against methicillin
      resistant clinical isolates strains of Staphylococcus aureus. MIC90, MIC50, as
      well as MBC90 and MBC50, for the lichen compounds were evaluated. The MIC90 was
      ranging from 32 ug/ml for perlatolic acid to 128 ug/ml for alpha-collatolic acid.
      MBC90 was ranging from onefold up to twofold the MIC90 for each compound. A
      synergistic action was observed in combination with gentamicin, whilst antagonism
      was observed for some lichen compounds in combination with levofloxacin. All
      combinations with erythromycin were indifferent, whilst variability was observed
      for clindamycin and oxacillin combinations. Data from checkerboard assay were
      analysed and interpreted using the fractional inhibitory concentration index and
      the response surface approach using the DeltaE model. Discrepancies were found
      between both methods for some combinations. These could mainly be explained by
      the failure of FIC approach, being too much subjective and sensitive to
      experimental errors. These findings suggest, however, that the natural compounds
      from lichens are good candidates for the individuation of novel templates for the
      development of new antimicrobial agents or combinations of drugs for
      chemotherapy. 

PMID- 25765827
TI  - Berberis aristata/Silybum marianum fixed combination (Berberol((r))) effects on
      lipid profile in dyslipidemic patients intolerant to statins at high dosages: a
      randomized, placebo-controlled, clinical trial.
AB  - AIM: to evaluate the efficacy of Berberis aristata/Silybum marianum
      (Berberol((r))) in a sample of dyslipidemic patients intolerant to statins at
      high dosages in a randomized, double blind, placebo-controlled clinical trial.
      METHODS: we enrolled 175 euglycemic, dyslipidemic subjects, intolerant to statins
      at high dosages. During the run-in period, statins were stopped for 1 month, then
      they were re-introduced at the half of the previously taken dose. After that,
      patients were randomized to placebo or Berberol((r)), 1 tablet during the lunch
      and 1 tablet during the dinner, for 6 months. Anthropometric, metabolic and
      inflammatory parameters were assessed at randomization, at 3 and 6 months.
      RESULTS: fasting plasma glucose, insulin, and HOMA-index levels were reduced by
      Berberol((r)), but not by placebo; moreover they were lower than the ones
      recorded with placebo. Total cholesterol, LDL-C, triglycerides, and
      myeloperoxidase did not change after 6 months since the reduction of statin
      dosage and the introduction of Berberol((r)), while they increased in the placebo
      group, and were higher compared to the ones obtained with active treatment. No
      patients had serious adverse events in both groups. CONCLUSIONS: our study
      displays the rationale of the combination of Berberol((r)) and a reduced dosage
      of statin for the treatment of hyperlipidemia in patients intolerant to statins
      at high dosage.

PMID- 25765828
TI  - Purification and cloning of lectin that induce cell apoptosis from Allium
      chinense.
AB  - A 8.7 kDa lectin with high agglutin activity was isolated by affinity
      chromatography and cloned from Allium chinense in this study. For the MTT assay,
      approximately 60 ug/ml A. chinense lectin (ACL) inhibited 50% of the human
      hepatoma Hep-3B cells grown after 48 h. In addition, no antiproliferative effect
      was observed on normal human umbilical vein endothelial cells (HUVEC) even at 100
      ug/ml concentration. After treatments with ACL on Hep-3B cells, morphologic
      changes in the nucleus and cytoskeleton were observed under laser scanning
      confocal microscopy with 4',6-diamidino-2-phenylindole and tubulin Alexa Fluor
      488 staining; whereas, the mitochondrial membrane potential was observed through
      Mito Tracker Red CMXRos staining. The results showed that ACL led to cell
      morphology and structure change (e.g., round cell shrinkage). Moreover, ACL
      resulted in significant change in the shape of the nucleus, damaged the
      cytoskeleton when tubulin was degraded, and reduced the mitochondrial
      transmembrane potential. By contrast, no changes were observed on HUVEC cells
      under the same treatment conditions. DNA fragmentation analysis was used to
      detect DNA damage. Western blot showed that ACL upregulated caspase-3 and Bax
      expression during apoptosis and cloned the structural gene of ACL with an open
      reading frame of 456 bp encoding 151 amino acid residues. The results showed that
      ACL is a potential anticancer drug. 

PMID- 25765829
TI  - Pharmacological synergism of bee venom and melittin with antibiotics and plant
      secondary metabolites against multi-drug resistant microbial pathogens.
AB  - The goal of this study was to investigate the antimicrobial activity of bee venom
      and its main component, melittin, alone or in two-drug and three-drug
      combinations with antibiotics (vancomycin, oxacillin, and amikacin) or
      antimicrobial plant secondary metabolites (carvacrol, benzyl isothiocyanate, the
      alkaloids sanguinarine and berberine) against drug-sensitive and antibiotic
      resistant microbial pathogens. The secondary metabolites were selected
      corresponding to the molecular targets to which they are directed, being
      different from those of melittin and the antibiotics. The minimal inhibitory
      concentration (MIC) and minimal bactericidal concentration (MBC) were evaluated
      by the standard broth microdilution method, while synergistic or additive
      interactions were assessed by checkerboard dilution and time-kill curve assays.
      Bee venom and melittin exhibited a broad spectrum of antibacterial activity
      against 51 strains of both Gram-positive and Gram-negative bacteria with strong
      anti-MRSA and anti-VRE activity (MIC values between 6 and 800 ug/ml). Moreover,
      bee venom and melittin showed significant antifungal activity (MIC values between
      30 and 100 ug/ml). Carvacrol displayed bactericidal activity, while BITC
      exhibited bacteriostatic activity against all MRSA and VRE strains tested
      (reference strains and clinical isolates), both compounds showed a remarkable
      fungicidal activity with minimum fungicidal concentration (MFC) values between 30
      and 200 ug/ml. The DNA intercalating alkaloid sanguinarine showed bactericidal
      activity against MRSA NCTC 10442 (MBC 20 ug/ml), while berberine exhibited
      bacteriostatic activity against MRSA NCTC 10442 (MIC 40 ug/ml). Checkerboard
      dilution tests mostly revealed synergism of two-drug combinations against all the
      tested microorganisms with FIC indexes between 0.24 and 0.50, except for rapidly
      growing mycobacteria in which combinations exerted an additive effect (FICI =
      0.75-1). In time-kill assays all three-drug combinations exhibited a powerful
      bactericidal synergistic effect against MRSA NCTC 10442, VRE ATCC 51299, and E.
      coli ATCC 25922 with a reduction of more than 3log10 in the colony count after 24
      h. Our findings suggest that bee venom and melittin synergistically enhanced the
      bactericidal effect of several antimicrobial agents when applied in combination
      especially when the drugs affect several and differing molecular targets. These
      results could lead to the development of novel or complementary antibacterial
      drugs against MDR pathogens. 

PMID- 25765830
TI  - Inhibitory effects of Saururus chinensis and its components on stomach cancer
      cells.
AB  - Saururus chinensis (SC) Baill. (Saururaceae), a perennial herb commonly called
      Chinese lizard's tail or Sam-baekcho in Korea, has been used in the treatment of
      edema, gonorrhea, jaundice, and inflammatory diseases. Recently, several reports
      have been commissioned to examine the anti-cancer activities of this plant. In
      this study, we evaluated the inhibitory activity and mechanism of action on SC
      and its components against stomach cancer cells. SC extracts displayed cytotoxic
      effects on AGS cells in a dose-dependent manner. Moreover, SC increased the
      number of annexin V-positive apoptotic bodies and phosphorylated JNK and p38 in
      AGS cells. SC also down-regulated anti-apoptotic (Bcl-2) genes and up-regulated
      apoptotic (Bax) genes in AGS cells. We further confirmed that caspase activation
      plays an important role in SC-induced apoptosis in AGS cells. Furthermore, we
      examined erythro-Austrobailignan-6 and meso-dihydroguaiaretic acid, major active
      constituents of SC, which induced apoptosis in both the AGS and NCI-N87 stomach
      cancer cell lines. Taken together, our data provide the evidence that SC and its
      components induce apoptosis in stomach cancer cells, making it a potential
      candidate as a chemotherapeutic drug. 

PMID- 25765831
TI  - Melissa officinalis extract induces apoptosis and inhibits proliferation in colon
      cancer cells through formation of reactive oxygen species.
AB  - PURPOSE: Efficient strategies for the prevention of colon cancer are extensively
      being explored, including dietary intervention and the development of novel
      phytopharmaceuticals. Safe extracts of edible plants contain structurally diverse
      molecules that can effectively interfere with multi-factorial diseases such as
      colon cancer. In this study, we describe the antiproliferative and proapoptotic
      effects of ethanolic lemon balm (Melissa officinalis) leaves extract in human
      colon carcinoma cells. We further investigated the role of extra- and
      intracellular reactive oxygen species (ROS). METHODS: Antitumor effects of lemon
      balm extract (LBE) were investigated in HT-29 and T84 human colon carcinoma
      cells. Inhibition of proliferation was analyzed by DNA quantification. The causal
      cell cycle arrest was determined by flow cytometry of propidium iodide-stained
      cells and by immunoblotting of cell cycle regulator proteins. To investigate
      apoptosis, cleavage of caspases 3 and 7 was detected by immunoblotting and
      fluorescence microscopy. Phosphatidylserine externalization was measured by
      Annexin V assays. Mechanistic insights were gained by measurement of ROS using
      the indicator dyes CM-H2DCFDA and Cell ROX Green. RESULTS: After 3 and 4 days of
      treatment, LBE inhibited the proliferation of HT-29 and T84 colon carcinoma cells
      with an inhibitory concentration (IC50) of 346 and 120 ug/ml, respectively.
      Antiproliferative effects were associated with a G2/M cell cycle arrest and
      reduced protein expression of cyclin dependent kinases (CDK) 2, 4, 6, cyclin D3,
      and induced expression of cyclin-dependent kinase inhibitor 2C (p18) and 1A
      (p21). LBE (600 ug/ml) induced cleavage of caspases 3 and 7 and
      phosphatidylserine externalization. LBE-induced apoptosis was further associated
      with formation of ROS, whereas quenching of ROS by antioxidants completely
      rescued the colon carcinoma cells from LBE-induced apoptosis. CONCLUSIONS: Lemon
      balm (Melissa officinalis) extract inhibits the proliferation of colon carcinoma
      cells and induces apoptosis through formation of ROS. Taken together, LBE or
      subfractions thereof could be used for the prevention of colon cancer.

PMID- 25765832
TI  - Oral administration of a Spirulina extract enriched for Braun-type lipoproteins
      protects mice against influenza A (H1N1) virus infection.
AB  - A growing body of research indicates that oral administration of bacteria (such
      as probiotics) can exhibit a protective effect against influenza A (H1N1) viral
      infection in mice. In the present study, we used a mouse model to examine whether
      oral administration of Immulina((r)), a commercial extract from the cyanobacteria
      Arthrospira (Spirulina) platensis, can reduce the severity of illness resulting
      from influenza A (H1N1) viral infection. The main active compounds within
      Immulina((r)) are bacterial Braun-type lipoproteins that activate innate immune
      cells through a toll-like receptor (TLR) 2-dependent pathway. Mice that were fed
      Immulina((r)) for 30 days before and 21 days after infection with influenza A
      (H1N1) virus exhibited a statistically significant reduction in the severity of
      infection. Compared to the control group, Immulina((r))-fed mice exhibited less
      weight loss, increased appetite, decreased clinical signs of disease, and lower
      lung histopathology scores. The results from the present study adds to the
      increasing evidence that oral administration of bacterial components that
      activate innate immune cells, whether derived from a bacterial preparation
      (probiotics or cyanobacteria) or from plant material containing endophytic
      bacteria, can exhibit a protective effect against influenza A (H1N1) viral
      infection. 

PMID- 25765833
TI  - Dendritic cells matured in the presence of the lycopodium alkaloid annotine
      direct T cell responses toward a Th2/Treg phenotype.
AB  - Annotine is a lycopodane-type alkaloid isolated from the Icelandic club moss
      Lycopodium annotinum ssp. alpestre. Annotine does not inhibit
      acetylcholinesterase, as some other lycopodium alkaloids do, and other
      bioactivities have not been reported. The aim of this study was to determine the
      effects of annotine on maturation of dendritic cells (DCs) and their ability to
      activate allogeneic CD4(+) T cells. Human monocyte-derived DCs were matured in
      the absence or presence of annotine at a concentration of 1, 10 or 100 MUg/ml.
      The effect of the annotine on maturation of the DCs was determined by measuring
      concentration of cytokines in culture supernatant by ELISA and expression of
      surface molecules by flow cytometry. DCs matured in the absence or presence of
      annotine at 100 ug/ml were also co-cultured with allogeneic CD4(+) T cells and
      concentration of cytokines in supernatants determined by ELISA and expression of
      surface molecules by flow cytometry. When cultured alone, DCs matured in the
      presence of annotine secreted less of the pro-inflammatory cytokines IL-6 and IL
      23 and had a tendency toward less secretion of IL-12p40 than DCs matured in the
      absence of annotine. However, when DCs were matured in the presence of annotine
      and then co-cultured with allogeneic CD4(+) T cells they secreted more IL-12p40
      and had a tendency toward secreting more IL-6 than DCs matured in the absence of
      annotine and then co-cultured with T cells. Allogeneic CD4(+) T cells co-cultured
      with DCs matured in the presence of annotine secreted more IL-13 than T cells co
      cultured with DCs matured in the absence of annotine, but stimulating the DCs in
      the presence of annotine did not affect T cell secretion of IFN-gamma and IL-17.
      There was also more IL-10 in co-cultures of T cells and DCs matured in the
      presence of annotine than in co-cultures of T cells and DCs matured in the
      absence of annotine. These results show that annotine increases the ability of
      DCs to direct the differentiation of allogeneic CD4(+) T cells toward a Th2/Treg
      phenotype, which may be of interest in the development of new treatments for Th1-
      and/or Th17-mediated inflammatory diseases. 

PMID- 25765834
TI  - Neuroprotective effect and underlying mechanism of sodium danshensu [3-(3,4
      dihydroxyphenyl) lactic acid from Radix and Rhizoma Salviae miltiorrhizae =
      Danshen] against cerebral ischemia and reperfusion injury in rats.
AB  - Sodium danshensu (SDSS), the sodium salt of danshensu (DSS), has the same
      pharmacological effects as DSS. In the present study, we aimed to investigate the
      neuroprotective effect and possible mechanism of SDSS against cerebral
      ischemic/reperfusion injury. Sprague-Dawley rats were randomly divided into four
      groups: sham, control, 30 mg/kg and 60 mg/kg SDSS. Cerebral ischemia was induced
      by 2 h of middle cerebral artery occlusion (MCAO). Neurological functional
      deficits were evaluated according to the modified neurological severity score
      (mNSS); cerebral infarct volume and histological damage were measured by TTC or H
      E staining. In addition, the number of apoptotic cells and caspase 3/7 activity
      were assessed by TUNEL or Caspase-Glo assay. And the expression of apoptosis
      regulatory proteins and the PI3K/Akt pathway were investigated by western
      blotting. Our results showed that treatment with SDSS for 5 days after MCAO
      remarkably improved neurologic deficits and survival rate, reduced infarct volume
      and the number of dead neurons. SDSS also decreased the number of apoptotic
      cells, regulated the expression of Bcl-2 and Bax, and increased the ratio of Bcl
      2/Bax. Further study revealed that treatment with SDSS also increased the level
      of p-Akt and p-GSK-3beta. Taken together, our results suggest that SDSS has the
      neuroprotective effect against cerebral I/R injury, and the potential mechanism
      might to inhibition of apoptosis through activating the PI3K/Akt signal pathway. 

PMID- 25765835
TI  - Effects of Silybum marianum (L.) Gaertn. (silymarin) extract supplementation on
      antioxidant status and hs-CRP in patients with type 2 diabetes mellitus: a
      randomized, triple-blind, placebo-controlled clinical trial.
AB  - AIM: Diabetes is a serious metabolic disorder and oxidative stress and
      inflammation contribute to its pathogenesis and complications. Since Silybum
      marianum (L.) Gaertn. (silymarin) extract is an antioxidant with anti
      inflammatory properties, this randomized clinical trial was conducted to evaluate
      the effects of silymarin supplementation on oxidative stress indices and hs-CRP
      in type 2 diabetes mellitus patients. METHODS: For the present paralleled,
      randomized, triple-blinded, placebo-controlled clinical trial, 40 type 2 diabetes
      patients aged 25-50 yr old and on stable medication were recruited from the
      Iranian Diabetes Society and endocrinology clinics in East Azarbayjan (Tabriz,
      Iran) and randomly assigned into two groups. Patients in the silymarin treatment
      group received 140 mg, thrice daily of dried extracts of Silybum marianum (n =
      20) and those in the placebo group (n = 20) received identical placebos for 45
      days. Data pertaining to height, weight, waist circumference and BMI, as well as
      food consumption, were collected at base line and at the conclusion of the study.
      Fasting blood samples were obtained and antioxidant indices and hs-CRP were
      assessed at baseline, as well as at the end of the trial. RESULTS: All 40
      patients completed the study and did not report any adverse effects or symptoms
      with the silymarin supplementation. Silymarin supplementation significantly
      increased superoxide dismutase (SOD), glutathione peroxidase (GPX) activity and
      total antioxidant capacity (TAC) compared to patients taking the placebo, by
      12.85%, 30.32% and 8.43%, respectively (p < 0.05). There was a significant
      reduction in hs-CRP levels by 26.83% (p < 0.05) in the silymarin group compared
      to the placebo group. Malondialdehyde (MDA) concentration significantly decreased
      by 12.01% (p < 0.05) in the silymarin group compared to the baseline.
      CONCLUSIONS: Silymarin supplementation improves some antioxidant indices (SOD,
      GPX and TAC) and decrease hs-CRP levels in T2DM patients.

PMID- 25765836
TI  - Cinnamic acid exerts anti-diabetic activity by improving glucose tolerance in
      vivo and by stimulating insulin secretion in vitro.
AB  - Although the anti-diabetic activity of cinnamic acid, a pure compound from
      cinnamon, has been reported but its mechanism(s) is not yet clear. The present
      study was designed to explore the possible mechanism(s) of anti-diabetic activity
      of cinnamic acid in in vitro and in vivo non-obese type 2 diabetic rats. Non
      obese type 2 diabetes was developed by injecting 90 mg/kg streptozotocin in 2-day
      old Wistar pups. Cinnamic acid and cinnamaldehyde were administered orally to
      diabetic rats for assessing acute blood glucose lowering effect and improvement
      of glucose tolerance. Additionally, insulin secretory activity of cinnamic acid
      and cinnamaldehyde was evaluated in isolated mice islets. Cinnamic acid, but not
      cinnamaldehyde, decreased blood glucose levels in diabetic rats in a time- and
      dose-dependent manner. Oral administration of cinnamic acid with 5 and 10 mg/kg
      doses to diabetic rats improved glucose tolerance in a dose-dependent manner. The
      improvement by 10 mg/kg cinnamic acid was comparable to that of standard drug
      glibenclamide (5 mg/kg). Further in vitro studies showed that cinnamaldehyde has
      little or no effect on glucose-stimulated insulin secretion; however, cinnamic
      acid significantly enhanced glucose-stimulated insulin secretion in isolated
      islets. In conclusion, it can be said that cinnamic acid exerts anti-diabetic
      activity by improving glucose tolerance in vivo and stimulating insulin secretion
      in vitro. 

PMID- 25765837
TI  - Natural lignans from Arctium lappa modulate P-glycoprotein efflux function in
      multidrug resistant cancer cells.
AB  - Arctium lappa is a well-known traditional medicinal plant in China (TCM) and
      Europe that has been used for thousands of years to treat arthritis, baldness or
      cancer. The plant produces lignans as secondary metabolites which have a wide
      range of bioactivities. Yet, their ability to reverse multidrug resistance (MDR)
      in cancer cells has not been explored. In this study, we isolated six lignans
      from A. lappa seeds, namely arctigenin, matairesinol, arctiin, (iso)lappaol A,
      lappaol C, and lappaol F. The MDR reversal potential of the isolated lignans and
      the underlying mechanism of action were studied using two MDR cancer cell lines,
      CaCo2 and CEM/ADR 5000 which overexpress P-gp and other ABC transporters. In two
      drug combinations of lignans with the cytotoxic doxorubicin, all lignans
      exhibited synergistic effects in CaCo2 cells and matairesinol, arctiin, lappaol C
      and lappaol F display synergistic activity in CEM/ADR 5000 cells. Additionally,
      in three-drug combinations of lignans with the saponin digitonin and doxorubicin
      MDR reversal activity was even stronger enhanced. The lignans can increase the
      retention of the P-gp substrate rhodamine 123 in CEM/ADR 5000 cells, indicating
      that lignans can inhibit the activity of P-gp. Our study provides a first insight
      into the potential chemosensitizing activity of a series of natural lignans,
      which might be candidates for developing novel adjuvant anticancer agents. 

PMID- 25765838
TI  - Cytotoxicity of the indole alkaloid reserpine from Rauwolfia serpentina against
      drug-resistant tumor cells.
AB  - BACKGROUND: The antihypertensive reserpine is an indole alkaloid from Rauwolfia
      serpentina and exerts also profound activity against cancer cells in vitro and in
      vivo. The present investigation was undertaken to investigate possible modes of
      action to explain its activity toward drug-resistant tumor cells. MATERIAL AND
      METHODS: Sensitive and drug-resistant tumor cell lines overexpressing P
      glycoprotein (ABCB1/MDR1), breast cancer resistance protein (ABCG2/BCRP),
      mutation-activated epidermal growth factor receptor (EGFR), wild-type and p53
      knockout cells as well as the NCI panel of cell lines from different tumor origin
      were analyzed. Reserpine's cytotoxicity was investigated by resazurin and
      sulforhodamine assays, flow cytometry, and COMPARE and hierarchical cluster
      analyses of transcriptome-wide microarray-based RNA expressions. RESULTS: P
      glycoprotein- or BCRP overexpressing tumor cells did not reveal cross-resistance
      to reserpine. EGFR-overexpressing cells were collateral sensitive and p53-
      Knockout cells cross-resistant to this drug compared to their wild-type parental
      cell lines. Reserpine increased the uptake of doxorubicin in P-glycoprotein
      overexpressing cells, indicating that reserpine inhibited the efflux function of
      P-glycoprotein. Using molecular docking, we found that reserpine bound with even
      higher binding energy to P-glycoprotein and EGFR than the control drugs verapamil
      (P-glycoprotein inhibitor) and erlotinib (EGFR inhibitor). COMPARE and cluster
      analyses of microarray data showed that the mRNA expression of a panel of genes
      predicted the sensitivity or resistance of the NCI tumor cell line panel with
      statistical significance. The genes belonged to diverse pathways and biological
      functions, e.g. cell survival and apoptosis, EGFR activation, regulation of
      angiogenesis, cell mobility, cell adhesion, immunological functions, mTOR
      signaling, and Wnt signaling. CONCLUSION: The lack of cross-resistance to most
      resistance mechanisms and the collateral sensitivity in EGFR-transfectants
      compared to wild-type cells speak for a promising role of reserpine in cancer
      chemotherapy. Reserpine deserves further consideration for cancer therapy in the
      clinical setting.

PMID- 25765839
TI  - Clinical tolerability and pharmacokinetics of Erigerontis hydroxybenzene
      injection: results of a randomized phase I study in healthy Chinese volunteers.
AB  - Multiple phenolic compounds in the extract of Erigeron breviscapus
      synergistically contribute to the neurovascular protective effects. We conducted
      a phase I and pharmacokinetic study with the phenolic compound-enriched product
      extracted from Erigeron breviscapus, Erigerontis hydroxybenzenes injection (EHI),
      in healthy Chinese volunteers. A randomized, open-label, single-center, double
      arm, dose-escalation study of EHI was conducted. The tolerability of
      intravenously EHI administrated in single- or multiple-dose (once daily for 7
      days) was studied in 40 healthy Chinese volunteers and the pharmacokinetics of
      EHI was studied in additional 10 volunteers. The tolerated dose of intravenous
      infusion of EHI in healthy Chinese volunteers was 6 vials (equivalent to 90 mg
      bioactive phenolic compounds). The main limitations to dose escalation of EHI
      were transit changes in electrocardiogram and mild, transit increase in alanine
      aminotransferase. After intravenous administration of EHI, the average systemic
      clearance of multiple phenolic compounds of scutellarin, 1,3-dicaffeoylquinic
      acid, 3,5-dicaffeoylquinic acid, and 3,4-dicaffeoylquinic acid were 131, 29, 262,
      112 L/h for male volunteers and 202, 28, 252, 117 L/h for female volunteers. The
      intervention of intravenous infusion of EHI in healthy Chinese volunteers was
      generally tolerated. The findings from this study provide data on the
      tolerability and pharmacokinetics of the extract from Erigeron breviscapus and
      support further trials. 

PMID- 25765841
TI  - Orientation-dependent changes in single motor neuron activity during adaptive
      soft-bodied locomotion.
AB  - Recent major advances in understanding the organizational principles underlying
      motor control have focused on a small number of animal species with stiff
      articulated skeletons. These model systems have the advantage of easily
      quantifiable mechanics, but the neural codes underlying different movements are
      difficult to characterize because they typically involve a large population of
      neurons controlling each muscle. As a result, studying how neural codes drive
      adaptive changes in behavior is extremely challenging. This problem is highly
      simplified in the tobacco hawkmoth Manduca sexta, which, in its larval stage
      (caterpillar), is predominantly soft-bodied. Since each M. sexta muscle is
      innervated by one, occasionally two, excitatory motor neurons, the electrical
      activity generated by each muscle can be mapped to individual motor neurons. In
      the present study, muscle activation patterns were converted into motor neuron
      frequency patterns by identifying single excitatory junction potentials within
      recorded electromyographic traces. This conversion was carried out with single
      motor neuron resolution thanks to the high signal selectivity of newly developed
      flexible microelectrode arrays, which were specifically designed to record from
      M. sexta muscles. It was discovered that the timing of motor neuron activity and
      gait kinematics depend on the orientation of the plane of motion during
      locomotion. We report that, during climbing, the motor neurons monitored in the
      present study shift their activity to correlate with movements in the animal's
      more anterior segments. This orientation-dependent shift in motor activity is in
      agreement with the expected shift in the propulsive forces required for climbing.
      Our results suggest that, contrary to what has been previously hypothesized,
      M.sexta uses central command timing for adaptive load compensation.

PMID- 25765840
TI  - Traditional herbal formula Jakyakgamcho-tang (Paeonia lactiflora and Glycyrrhiza
      uralensis) impairs inflammatory chemokine production by inhibiting activation of
      STAT1 and NF-kappaB in HaCaT cells.
AB  - A traditional herbal formula Jakyakgamcho-tang (JYGCT; Paeonia lactiflora and
      Glycyrrhiza uralensis) has been used for treatment of backache, muscle pain,
      acute abdominal pain, neuralgia, bronchial asthma, and painful peripheral
      neuropathy in Oriental medicine. We report on our experiments using the HaCaT
      human keratinocyte cell line showing that a traditional herbal formula JYGCT has
      inhibitory effects on inflammatory responses in skin. Stimulation with tumour
      necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma) caused a
      significant increase in the production of the following chemokines: thymus- and
      activation-regulated chemokine (TARC)/CCL17; macrophage-derived chemokine
      (MDC)/CCL22; regulated on activation, normal T-cell expressed and secreted
      (RANTES)/CCL5; and interleukin-8 (IL-8) in HaCaT cells. By contrast, treatment
      with JYGCT extract significantly reduced the production of TARC, MDC, RANTES, and
      IL-8, but caused no cytotoxicity, compared with TNF-alpha and IFN-gamma-treated
      control cells. Consistently, JYGCT extract downregulated the mRNA expression of
      TARC, MDC, RANTES, and IL-8 induced by TNF-alpha and IFN-gamma in a dose
      dependent manner. In addition, TNF-alpha and IFN-gamma markedly increased the
      phosphorylation of signal transducer and activator of transcription 1 (STAT1) and
      the nuclear translocation of nuclear factor kappa B (NF-kappaB) in HaCaT cells.
      By contrast, TNF-alpha and IFN-gamma-induced activation of STAT1 and NF-kappaB
      activation was inhibited by JYGCT treatment in a dose-dependent manner. Our data
      indicate that JYGCT attenuates TNF-alpha and IFN-gamma-mediated chemokine
      production by targeting the STAT1 and NF-kappaB signalling in keratinocytes. Our
      findings suggest that JYGCT has potential as a therapeutic drug candidate for the
      treatment of inflammatory skin diseases. 

PMID- 25765842
TI  - Biosynthesis of soluble carotenoid holoproteins in Escherichia coli.
AB  - Carotenoids are widely distributed natural pigments that are excellent
      antioxidants acting in photoprotection. They are typically solubilized in
      membranes or attached to proteins. In cyanobacteria, the photoactive soluble
      Orange Carotenoid Protein (OCP) is involved in photoprotective mechanisms as a
      highly active singlet oxygen and excitation energy quencher. Here we describe a
      method for producing large amounts of holo-OCP in E.coli. The six different genes
      involved in the synthesis of holo-OCP were introduced into E. coli using three
      different plasmids. The choice of promoters and the order of gene induction were
      important: the induction of genes involved in carotenoid synthesis must precede
      the induction of the ocp gene in order to obtain holo-OCPs. Active holo-OCPs with
      primary structures derived from several cyanobacterial strains and containing
      different carotenoids were isolated. This approach for rapid heterologous
      synthesis of large quantities of carotenoproteins is a fundamental advance in the
      production of antioxidants of great interest to the pharmaceutical and cosmetic
      industries.

PMID- 25765844
TI  - Aggregates of silicon quantum dots as a drug carrier: selective intracellular
      drug release based on pH-responsive aggregation/dispersion.
AB  - Using amine-modified silicon quantum dots (Si-QDs) with visible photoluminescence
      as a building block, drug-loaded Si-QD aggregates were assembled. The aggregates
      were designed to break down in response to the endosomal pH decrease, which
      enabled the selective intracellular release of the loaded drugs. 

PMID- 25765843
TI  - 3-Iodothyroacetic acid lacks thermoregulatory and cardiovascular effects in vivo.
AB  - BACKGROUND AND PURPOSE: 3-Iodothyronamine (3-T1 AM) is an endogenous thyroid
      hormone derivative reported to induce strong hypothermia and bradycardia within
      minutes upon injection in rodents. Although 3-T1 AM is rapidly converted to
      several other metabolites in vivo, these strong pharmacological responses were
      solely attributed to 3-T1 AM, leaving potential contributions of downstream
      products untested. We therefore examined the cardiometabolic effects of 3
      iodothyroacetic acid (TA1 ), the main degradation product of 3-T1 AM.
      EXPERIMENTAL APPROACH: We used a sensitive implantable radiotelemetry system in
      C57/Bl6J mice to study the effects of TA1 on body temperature and heart rate, as
      well as other metabolic parameters. KEY RESULTS: Interestingly, despite using
      pharmacological TA1 doses, we observed no effects on heart rate or body
      temperature after a single TA1 injection (50 mg.kg(-1) , i.p.) compared to sham
      injected controls. Repeated administration of TA1 (5 mg.kg(-1) , i.p. for 7 days)
      likewise did not alter body weight, food and water intake, heart rate, blood
      pressure, brown adipose tissue (BAT) thermogenesis or body temperature. Moreover,
      mRNA expression of tissue specific genes in heart, kidney, liver, BAT and lung
      was also not altered by TA1 compared to sham-injected controls. CONCLUSIONS AND
      IMPLICATIONS: Our data therefore conclusively demonstrate that TA1 does not
      contribute to the cardiovascular or thermoregulatory effects observed after 3-T1
      AM administration in mice, suggesting that the oxidative deamination constitutes
      an important deactivation mechanism for 3-T1 AM with possible implications for
      cardiovascular and thermoregulatory functions.

PMID- 25765845
TI  - Diagnosis and management of persistent pulmonary hypertension of the newborn.
AB  - Persistent pulmonary hypertension of new born (PPHN) is associated with mortality
      and morbidity; it may be idiopathic or secondary to a number of conditions. The
      mainstay of diagnosis and to exclude structural abnormalities is
      echocardiography. Brain type natriuretic peptide (BNP) levels are elevated in
      PPHN, but are insufficiently sensitive to contribute to routine diagnosis.
      Management includes improving oxygenation by optimising lung volume by
      ventilatory techniques and/or surfactant and administering pulmonary vasodilator
      agents. Inhaled nitric oxide (iNO), a selective pulmonary vasodilator, reduces
      the need for extracorporeal membrane oxygenation in term infants; it does not,
      however, improve mortality or have any long term positive effects in prematurely
      born infants or infants with congenital diaphragmatic hernia. Other pulmonary
      vasodilators have been reported in case series to be efficacious alone or in
      combination with iNO. Randomised trials with long term follow up are required to
      identify the optimum therapeutic strategies in PPHN. 

PMID- 25765846
TI  - Recurrent FXYD2 p.Gly41Arg mutation in patients with isolated dominant
      hypomagnesaemia.
AB  - BACKGROUND: Magnesium (Mg(2+)) is an essential ion for cell growth,
      neuroplasticity and muscle contraction. Blood Mg(2+) levels <0.7 mmol/L may cause
      a heterogeneous clinical phenotype, including muscle cramps and epilepsy and
      disturbances in K(+) and Ca(2+) homeostasis. Over the last decade, the genetic
      origin of several familial forms of hypomagnesaemia has been found. In 2000,
      mutations in FXYD2, encoding the gamma-subunit of the Na(+)-K(+)-ATPase, were
      identified to cause isolated dominant hypomagnesaemia (IDH) in a large Dutch
      family suffering from hypomagnesaemia, hypocalciuria and chondrocalcinosis.
      However, no additional patients have been identified since then. METHODS: Here,
      two families with hypomagnesaemia and hypocalciuria were screened for mutations
      in the FXYD2 gene. Moreover, the patients were clinically and genetically
      characterized. RESULTS: We report a p.Gly41Arg FXYD2 mutation in two families
      with hypomagnesaemia and hypocalciuria. Interestingly, this is the same mutation
      as was described in the original study. As in the initial family, several
      patients suffered from muscle cramps, chondrocalcinosis and epilepsy. Haplotype
      analysis revealed an overlapping haplotype in all families, suggesting a founder
      effect. CONCLUSIONS: The recurrent p.Gly41Arg FXYD2 mutation in two new families
      with IDH confirms that FXYD2 mutation causes hypomagnesaemia. Until now, no other
      FXYD2 mutations have been reported which could indicate that other FXYD2
      mutations will not cause hypomagnesaemia or are embryonically lethal.

PMID- 25765848
TI  - Salvage radical prostatectomy after external beam radiation therapy: a systematic
      review of current approaches.
AB  - BACKGROUND: Radical external beam radiotherapy (EBRT) is a standard treatment for
      prostate cancer patients. Despite this, the rate of intraprostatic relapses after
      primary EBRT is still not negligible. There is no consensus on the most
      appropriate management of these patients after EBRT failure. For these patients,
      local salvage therapy such as radical prostatectomy, cryotherapy, and
      brachytherapy may be indicated. OBJECTIVE: The objectives of this review were to
      analyze the eligibility criteria for careful selection of appropriate patients
      and to evaluate the oncological results and complications for each method.
      METHODS: A review of the literature was performed to identify studies of local
      salvage therapy for patients who had failed primary EBRT for localized prostate
      cancer. RESULTS: Most studies demonstrated that local salvage therapy after EBRT
      may provide long-term local control in appropriately selected patients, although
      toxicity is often significant. CONCLUSIONS: Our results suggest that for
      localized prostate cancer recurrence after EBRT, the selection of a local
      treatment modality should be made on a patient-by-patient basis. An improvement
      in selection criteria and an integrated definition of biochemical failure for all
      salvage methods are required to determine which provides the best oncological
      outcome and least comorbidity.

PMID- 25765847
TI  - Parathyroid hormone resets the cartilage circadian clock of the organ-cultured
      murine femur.
AB  - BACKGROUND AND PURPOSE: The circadian clock governs endogenous day-night
      variations. In bone, the metabolism and growth show diurnal rhythms. The
      circadian clock is based on a transcription-translation feedback loop composed of
      clock genes including Period2 (Per2), which encodes the protein period circadian
      protein homolog 2. Because plasma parathyroid hormone (PTH) levels show diurnal
      variation, we hypothesized that PTH could carry the time information to bone and
      cartilage. In this study, we analyzed the effect of PTH on the circadian clock of
      the femur. PATIENTS AND METHODS: Per2::Luciferase (Per2::Luc) knock-in mice were
      used and their femurs were organ-cultured. The bioluminescence was measured using
      photomultiplier tube-based real-time bioluminescence monitoring equipment or real
      time bioluminescence microscopic imaging devices. PTH or its vehicle was
      administered and the phase shifts were calculated. Immunohistochemistry was
      performed to detect PTH type 1 receptor (PTH1R) expression. RESULTS: Real-time
      bioluminescence monitoring revealed that PTH reset the circadian rhythm of the
      Per2::Luc activity in the femurs in an administration time-dependent and dose
      dependent manner. Microscopic bioluminescence imaging revealed that Per2::Luc
      activity in the growth plate and the articular cartilage showed that the
      circadian rhythms and their phase shifts were induced by PTH. PTH1R was expressed
      in the growth plate cartilage. INTERPRETATION: In clinical practice, teriparatide
      (PTH (1-34)) treatment is widely used for osteoporosis. We found that PTH
      administration regulated the femoral circadian clock oscillation, particularly in
      the cartilage. Regulation of the local circadian clock by PTH may lead to a more
      effective treatment for not only osteoporosis but also endochondral ossification
      in bone growth and fracture repair.

PMID- 25765849
TI  - A clonotypic Vgamma4Jgamma1/Vdelta5Ddelta2Jdelta1 innate gammadelta T-cell
      population restricted to the CCR6+CD27- subset.
AB  - Here we investigate the TCR repertoire of mouse Vgamma4(+) gammadelta T cells in
      correlation with their developmental origin and homeostasis. By deep sequencing
      we identify a high frequency of straight Vdelta5Ddelta2Jdelta1 germline
      rearrangements without P- and N-nucleotides within the otherwise highly diverse
      Trd repertoire of Vgamma4(+) cells. This sequence is infrequent in CCR6(-)CD27(+)
      cells, but abundant among CCR6(+)CD27(-) gammadelta T cells. Using an inducible
      Rag1 knock-in mouse model, we show that gammadelta T cells generated in the adult
      thymus rarely contain this germline-rearranged Vdelta5Ddelta2Jdelta1 sequence,
      confirming its fetal origin. Single-cell analysis and deep sequencing of the Trg
      locus reveal a dominant CDR3 junctional motif that completes the TCR repertoire
      of invariant Vgamma4(+)Vdelta5(+) cells. In conclusion, this study identifies an
      innate subset of fetal thymus-derived gammadelta T cells with an invariant
      Vgamma4(+)Vdelta5(+) TCR that is restricted to the CCR6(+)CD27(-) subset of
      gammadelta T cells. 

PMID- 25765850
TI  - Transcriptomic response to heat stress among ecologically divergent populations
      of redband trout.
AB  - BACKGROUND: As ectothermic organisms have evolved to differing aquatic climates,
      the molecular basis of thermal adaptation is a key area of research. In this
      study, we tested for differential transcriptional response of ecologically
      divergent populations of redband trout (Oncorhynchus mykiss gairdneri) that have
      evolved in desert and montane climates. Each pure strain and their F1 cross were
      reared in a common garden environment and exposed over four weeks to diel water
      temperatures that were similar to those experienced in desert climates within the
      species' range. Gill tissues were collected from the three strains of fish
      (desert, montane, F1 crosses) at the peak of heat stress and tested for mRNA
      expression differences across the transcriptome with RNA-seq. RESULTS: Strong
      differences in transcriptomic response to heat stress were observed across
      strains confirming that fish from desert environments have evolved diverse
      mechanisms to cope with stressful environments. As expected, a large number of
      total transcripts (12,814) were differentially expressed in the study (FDR <=
      0.05) with 2310 transcripts in common for all three strains, but the desert
      strain had a larger number of unique differentially expressed transcripts (2875)
      than the montane (1982) or the F1 (2355) strain. Strongly differentiated genes
      (>4 fold change and FDR <= 0.05) were particularly abundant in the desert strain
      (824 unique contigs) relative to the other two strains (montane = 58; F1 = 192).
      CONCLUSIONS: This study demonstrated patterns of acclimation (i.e., phenotypic
      plasticity) within strains and evolutionary adaptation among strains in numerous
      genes throughout the transcriptome. Key stress response genes such as molecular
      chaperones (i.e., heat shock proteins) had adaptive patterns of gene expression
      among strains, but also a much higher number of metabolic and cellular process
      genes were differentially expressed in the desert strain demonstrating these
      biological pathways are critical for thermal adaptation to warm aquatic climates.
      The results of this study further elucidate the molecular basis for thermal
      adaptation in aquatic ecosystems and extend the potential for identifying genes
      that may be critical for adaptation to changing climates.

PMID- 25765851
TI  - The daidzein- and estradiol- induced anorectic action in CCK or leptin receptor
      deficiency rats.
AB  - We investigated the effect of daidzein feeding and estradiol treatment on food
      intake in cholecystokinin-1 receptor (CCK1R) deficiency, leptin receptor (ObRb)
      deficiency rats and their wild-type rats. These rats underwent an ovariectomy or
      a sham operation. For the 5 week experiment, each rat was divided in three
      groups: control, daidzein (150 mg/kg diet), and estradiol (4.2 MUg/rat/day)
      groups. In both CCK1R+ and CCK1R- rats, daidzein feeding and estradiol treatment
      significantly decreased food intake. Daidzein feeding significantly reduced food
      intake in ovariectomized ObRb- rats, although not in ObRb+ rats. Estradiol
      treatment significantly lowered food intake in ovariectomized ObRb+ and ObRb-
      rats. In the ovariectomized rats, estradiol treatment significantly increases
      uterine weight, while daidzein feeding did not change it, suggesting that
      daidzein might have no or weak estrogenic effect in our experiment. These results
      suggest that CCK1R and ObRb signalings were not essential for the daidzein- and
      estradiol-induced anorectic action.

PMID- 25765852
TI  - Value and limitations of chimney grafts to treat arch lesions.
AB  - AIM: The endovascular debranching with chimney stents provides a minimally
      invasive alternative to open surgery with readily available devices and has
      extended the option of endoluminal therapy into the realm of the aortic arch. But
      a critical observation at the use of this technique at the aortic arch is
      important and necessary because of the lack of long-term results and long term
      patency of the stents. Our study aims to review the results of chimney grafts to
      treat arch lesions. METHODS: A systematic health database search was performed in
      December 2014 according to the Prisma Guidelines. Papers were sought through a
      meticulous search of the MEDLINE database (National Library of Medicine,
      Bethesda, MA) using the Pubmed search engine. RESULTS: Twenty-two articles were
      eligible for detailed analysis and data extraction. A total of 182 patients
      underwent chimney techniques during TEVAR (Thoracic Endovascular Aneurysm
      Repair). A total of 217 chimney grafts were implanted: 36 to the IA, 1 to the
      RCCA, 91 to the LCCA and 89 to the LSA. The type of stent-graft used for TEVAR
      was described in 132 patients. The type and name of chimney graft was described
      in 126 patients. In 53 patients information was limited to the type. Primary
      technical success, defined as a complete chimney procedure was achieved in 171
      patients (98%). In 8 patients it was not clearly reported. The overall stroke
      rate was 5.3%. The overall endoleak rate, in those papers were it was clearly
      reported, was 18.4% (31 patients); 23(13,6%) patients developed a type IA
      endoleak, 1 patient (0.6%) developed type IB endoleak and 7 patients (4.1%)
      developed a type II endoleak CONCLUSION: The total endovascular aortic arch
      debranching technique represent a good option to treat high-risk patients,
      because it dramatically reduces the aggressiveness of the procedure in the arch.
      Many concerns are still present, mainly related to durability and material
      interaction during time. Long-term follow-up is exceptionally important in light
      of the interactions of the stents, the thoracic endograft, the aortic arch, and
      every variation in systolic and diastolic pressure. Actually this technique has
      acceptable short and mid-term results. Long term data are available just from a
      very small number of patients and more data from a wider number are needed in
      order to embrace this method as a safe one.

PMID- 25765853
TI  - Relative adrenal insufficiency in patients with cirrhosis and variceal bleeding.

PMID- 25765855
TI  - TP53 Y220C Is a Hotspot Mutation in Oropharyngeal Squamous Cell Carcinoma.
AB  - OBJECTIVES: Although TP53 mutations in head and neck squamous cell carcinoma
      (HNSCC) have been extensively studied, their association with the different
      subsites in the head and neck region has never been described. METHODS: Sanger
      sequence analysis evaluating exons 4-9 in the TP53 gene was performed on 116
      HNSCC patients. The exon location, exact codon and corresponding substitution in
      relation to the anatomical site (subsite) of the HNSCC were evaluated. RESULTS:
      We found nonsynonymous TP53 mutations in 70% (81/116) of the patients. In oral
      cavity carcinomas, most mutations occurred in exon 7 (37%). In oropharyngeal and
      laryngeal tumors, mutations were mainly found in exons 6 and 7. The most common
      mutation was located in codon 220, and all of these were an Y220C mutation. Five
      out of nine (56%) Y220C mutations occurred in oropharyngeal tumors. Additionally,
      22% of all mutations observed in oropharyngeal squamous cell carcinoma (OPSCC)
      consisted of Y220C mutations. CONCLUSION: In this study, the subsite-related
      distribution of TP53 mutations underlines the biological diversity between tumors
      arising from different anatomical regions in the head and neck region. Moreover,
      the Y220C mutation was by far the most prevalent TP53 mutation in HNSCC and a
      relative hotspot mutation in the oropharynx. (c) 2015 S. Karger AG, Basel.

PMID- 25765854
TI  - Organizational metrics of interchromatin speckle factor domains: integrative
      classifier for stem cell adhesion & lineage signaling.
AB  - Stem cell fates on biomaterials are influenced by the complex confluence of
      microenvironmental cues emanating from soluble growth factors, cell-to-cell
      contacts, and biomaterial properties. Cell-microenvironment interactions
      influence the cell fate by initiating a series of outside-in signaling events
      that traverse from the focal adhesions to the nucleus via the cytoskeleton and
      modulate the sub-nuclear protein organization and gene expression. Here, we
      report a novel imaging-based framework that highlights the spatial organization
      of sub-nuclear proteins, specifically the splicing factor SC-35 in the
      nucleoplasm, as an integrative marker to distinguish between minute differences
      of stem cell lineage pathways in response to stimulatory soluble factors, surface
      topologies, and microscale topographies. This framework involves the high
      resolution image acquisition of SC-35 domains and imaging-based feature
      extraction to obtain quantitative nuclear metrics in tandem with machine learning
      approaches to generate a predictive cell state classification model. The acquired
      SC-35 metrics led to >90% correct classification of emergent human mesenchymal
      stem cell (hMSC) phenotypes in populations of hMSCs exposed for merely 3 days to
      basal, adipogenic, or osteogenic soluble cues, as well as varying levels of
      dexamethasone-induced alkaline phosphatase (ALP) expression. Early osteogenic
      cellular responses across a series of surface patterns, fibrous scaffolds, and
      micropillars were also detected and classified using this imaging-based
      methodology. Complex cell states resulting from inhibition of RhoGTPase, beta
      catenin, and FAK could be classified with >90% sensitivity on the basis of
      differences in the SC-35 organizational metrics. This indicates that SC-35
      organization is sensitively impacted by adhesion-related signaling molecules that
      regulate osteogenic differentiation. Our results show that diverse
      microenvironment cues affect different attributes of the SC-35 organizational
      metrics and lead to distinct emergent organizational patterns. Taken together,
      these studies demonstrate that the early organization of SC-35 domains could
      serve as a "fingerprint" of the intracellular mechanotransductive signaling that
      governs growth factor- and topography-responsive stem cell states. 

PMID- 25765856
TI  - Effect of microwave treatment on the efficacy of expeller pressing of Brassica
      napus rapeseed and Brassica juncea mustard seeds.
AB  - A study was conducted to evaluate the effect of microwave heating on the efficacy
      of expeller pressing of rapeseed and mustard seed and the composition of expeller
      meals in two types of Brassica napus rapeseed (intermediate- and low
      glucosinolate) and in Brassica juncea mustard (high-glucosinolate). Following
      microwave treatment, the microstructure of rapeseed using transmission electron
      microscopy showed a significant disappearance of oil bodies and myrosin cells.
      After 6 min of microwave heating (400 g, 800 W), the oil content of rapeseed
      expeller meal decreased from 44.9 to 13.5% for intermediate-glucosinolate B.
      napus rapeseed, from 42.6 to 11.3% for low-glucosinolate B. napus rapeseed, and
      from 44.4 to 14.1% for B. juncea mustard. The latter values were much lower than
      the oil contents of the corresponding expeller meals derived from the unheated
      seeds (i.e., 26.6, 22.6, and 29.8%, respectively). Neutral detergent fiber (NDF)
      contents showed no differences except for the expeller meal from the intermediate
      glucosinolate B. napus rapeseed, which increased from 22.7 to 29.2% after 6 min
      of microwave heating. Microwave treatment for 4 and 5 min effectively inactivated
      myrosinase enzyme of intermediate-glucosinolate B. napus rapeseed and B. juncea
      mustard seed, respectively. In low-glucosinolate B. napus rapeseed the enzyme
      appeared to be more heat stable, with some activity being present after 6 min of
      microwave heating. Myrosinase enzyme inactivation had a profound effect on the
      glucosinolate content of expeller meals and prevented their hydrolysis to toxic
      breakdown products during the expelling process. It appeared evident from this
      study that microwave heating for 6 min was an effective method of producing
      expeller meal without toxic glucosinolate breakdown products while at the same
      time facilitating high yield of oil during the expelling process.

PMID- 25765857
TI  - Natural quasicrystal with decagonal symmetry.
AB  - We report the first occurrence of a natural quasicrystal with decagonal symmetry.
      The quasicrystal, with composition Al71Ni24Fe5, was discovered in the Khatyrka
      meteorite, a recently described CV3 carbonaceous chondrite. Icosahedrite,
      Al63Cu24Fe13, the first natural quasicrystal to be identified, was found in the
      same meteorite. The new quasicrystal was found associated with steinhardtite
      (Al38Ni32Fe30), Fe-poor steinhardtite (Al50Ni40Fe10), Al-bearing trevorite
      (NiFe2O4) and Al-bearing taenite (FeNi). Laboratory studies of decagonal
      Al71Ni24Fe5 have shown that it is stable over a narrow range of temperatures,
      1120 K to 1200 K at standard pressure, providing support for our earlier
      conclusion that the Khatyrka meteorite reached heterogeneous high temperatures
      [1100 < T(K) <= 1500] and then rapidly cooled after being heated during an impact
      induced shock that occurred in outer space 4.5 Gya. The occurrences of metallic
      Al alloyed with Cu, Ni, and Fe raises new questions regarding conditions that can
      be achieved in the early solar nebula.

PMID- 25765858
TI  - Evaluation of methods for the estimation of threshold concentrations by the skin
      prick test.
AB  - BACKGROUND: The allergen dose-response curve is flat; thus, small changes in
      wheal size reflect large differences in skin sensitivity. The sensitivity as
      measured by provocation tests is given by the threshold concentration that causes
      symptoms and/or objective signs. The threshold concentrations differ by several
      magnitudes between the most and the least sensitive individuals clinically
      allergic to the same allergen. Variation in technique can be minimized by
      relating allergen responses to that to histamine. The aim here is to present and
      validate simple methods for estimation of the skin sensitivity given as the
      concentration inducing a wheal of the same size as that with the positive
      reference, 10 mg/ml of histamine HCl, in the same patient. METHODS: Data from
      previously reported trials on the biological equilibration of allergen extracts
      were used to document a method to calculate the concentration of allergen
      required to induce a wheal of the same size as that with 10 mg/ml of histamine
      dihydrochloride in the same patient, and to validate the methods using the
      parallel line bioassay as the gold standard. RESULTS: The validated methods
      correlated well with the results obtained using the gold standard method and
      provide results of skin prick testing based on threshold concentrations of
      allergen. CONCLUSIONS: The validated methods reduce the error of differences in
      testing techniques and make it possible to report skin sensitivity at threshold
      concentrations. A simple method to be used in clinical practice and a method
      suitable to describe changes in skin reactivity over time or during treatment are
      proposed.

PMID- 25765859
TI  - Pericardial effusion and sepsis caused by Staphylococcus schleiferi.

PMID- 25765860
TI  - A comprehensive evaluation of ensembl, RefSeq, and UCSC annotations in the
      context of RNA-seq read mapping and gene quantification.
AB  - BACKGROUND: RNA-Seq has become increasingly popular in transcriptome profiling.
      One aspect of transcriptome research is to quantify the expression levels of
      genomic elements, such as genes, their transcripts and exons. Acquiring a
      transcriptome expression profile requires genomic elements to be defined in the
      context of the genome. Multiple human genome annotation databases exist,
      including RefGene (RefSeq Gene), Ensembl, and the UCSC annotation database. The
      impact of the choice of an annotation on estimating gene expression remains
      insufficiently investigated. RESULTS: In this paper, we systematically
      characterized the impact of genome annotation choice on read mapping and
      transcriptome quantification by analyzing a RNA-Seq dataset generated by the
      Human Body Map 2.0 Project. The impact of a gene model on mapping of non-junction
      reads is different from junction reads. For the RNA-Seq dataset with a read
      length of 75 bp, on average, 95% of non-junction reads were mapped to exactly the
      same genomic location regardless of which gene models was used. By contrast, this
      percentage dropped to 53% for junction reads. In addition, about 30% of junction
      reads failed to align without the assistance of a gene model, while 10-15% mapped
      alternatively. There are 21,958 common genes among RefGene, Ensembl, and UCSC
      annotations. When we compared the gene quantification results in RefGene and
      Ensembl annotations, 20% of genes are not expressed, and thus have a zero count
      in both annotations. Surprisingly, identical gene quantification results were
      obtained for only 16.3% (about one sixth) of genes. Approximately 28.1% of genes'
      expression levels differed by 5% or higher, and of those, the relative expression
      levels for 9.3% of genes (equivalent to 2038) differed by 50% or greater. The
      case studies revealed that the gene definition differences in gene models
      frequently result in inconsistency in gene quantification. CONCLUSIONS: We
      demonstrated that the choice of a gene model has a dramatic effect on both gene
      quantification and differential analysis. Our research will help RNA-Seq data
      analysts to make an informed choice of gene model in practical RNA-Seq data
      analysis.

PMID- 25765861
TI  - Hepatitis B and C virus infection in the hemodialysis population from three
      romanian regions.
AB  - BACKGROUND: After 10 years of systematically nationwide applied measures for
      reduction of infection risk, in this national prospective observational study, we
      reassessed the prevalence of hepatitis virus infection prevalence and its
      influence on the outcome of end-stage kidney disease (ESKD) patients treated with
      hemodialysis. METHODS: Six-hundred ESKD patients (332 men and 268 women, median
      age 56 years) treated with chronic HD in seven centers from all the historical
      regions of Romania have been assigned to this study on 1st of November 2010. The
      aims of this study were to reevaluate the prevalence of the hepatitis B and C
      virus infection in a HD population from Romania after 10 years of systematically
      nationwide applied measures for reduction of infection risk and also to assess
      the impact of these infections on the prognosis of HD patients. RESULTS: HBsAg
      was positive in 9.5% (n = 57) of the patients, anti-HCV antibodies were detected
      in 27.3% (n = 164) and 5% (n = 30) were positive for both HBV and HCV infection.
      The mortality risk was significantly influenced only by age, the presence of
      coronary artery disease and the 25 OH vitamin D levels. CONCLUSIONS: This study
      shows that the systematically nationwide applied measures for reduction of
      infection risk significantly decreased HV infection prevalence in HD patients in
      Romania. The presence of HV infection did not significantly influence the
      mortality risk in this population.

PMID- 25765862
TI  - The Effect of Voice Ambulatory Biofeedback on the Daily Performance and Retention
      of a Modified Vocal Motor Behavior in Participants With Normal Voices.
AB  - PURPOSE: Ambulatory biofeedback has potential to improve carryover of newly
      established vocal motor behaviors into daily life outside of the clinic and
      warrants systematic research that is lacking in the literature. This proof-of
      concept study was designed to establish an empirical basis for future work in
      this area by formally assessing whether ambulatory biofeedback reduces daily
      vocal intensity (performance) and the extent to which this change remains after
      biofeedback removal (retention). METHOD: Six participants with normal voices wore
      the KayPENTAX Ambulatory Phonation Monitor for 3 baseline days followed by 4 days
      with biofeedback provided on odd days. RESULTS: Compared to baseline days,
      participants exhibited a statistically significant decrease in mean vocal
      intensity (4.4 dB) and an increase in compliance (16.8 percentage points) when
      biofeedback was provided above a participant-specific intensity threshold. After
      biofeedback removal, mean vocal intensity and compliance reverted back to
      baseline levels. CONCLUSIONS: These findings suggest that although current
      ambulatory biofeedback approaches have potential to modify a vocal motor
      behavior, the modified behavior may not be retained after biofeedback removal.
      Future work calls for the testing of more innovative ambulatory biofeedback
      approaches on the basis of motor control and learning theories to improve
      retention of a desired vocal motor behavior.

PMID- 25765864
TI  - Cell-free nucleic acids as non-invasive biomarkers of gynecological disorders,
      fetal aneuploidy and constitutional maternal chromosomal mosaicism.

PMID- 25765865
TI  - Reply: Cell-free nucleic acids as non-invasive biomarkers of gynecological
      disorders, fetal aneuploidy and constitutional maternal chromosomal mosaicism.

PMID- 25765863
TI  - Endometriosis: a high-risk population for major chronic diseases?
AB  - BACKGROUND: Despite an estimated prevalence of 10% in women, the etiology of
      endometriosis remains poorly understood. Over recent decades, endometriosis has
      been associated with risk of several chronic diseases, such as cancer, autoimmune
      diseases, asthma/atopic diseases and cardiovascular diseases. A deeper
      understanding of these associations is needed as they may provide new leads into
      the causes or consequences of endometriosis. This review summarizes the available
      epidemiological findings on the associations between endometriosis and other
      chronic diseases and discusses hypotheses for underlying mechanisms, potential
      sources of bias and methodological complexities. METHODS: We performed a
      comprehensive search of the PubMed/Medline and ISI Web of Knowledge databases for
      all studies reporting on the associations between endometriosis and other
      diseases published in English through to May 2014, using numerous search terms.
      We additionally examined the reference lists of all identified papers to capture
      any additional articles that were not identified through computer searches.
      RESULTS: We identified 21 studies on the associations between endometriosis and
      ovarian cancer, 14 for breast cancer, 8 for endometrial cancer, 4 for cervical
      cancer, 12 for cutaneous melanoma and 3 for non-Hodgkin's lymphoma, as well as 9
      on the links between endometriosis and autoimmune diseases, 6 on the links with
      asthma and atopic diseases, and 4 on the links with cardiovascular diseases.
      Endometriosis patients were reported to be at higher risk of ovarian and breast
      cancers, cutaneous melanoma, asthma, and some autoimmune, cardiovascular and
      atopic diseases, and at decreased risk of cervical cancer. CONCLUSIONS:
      Increasing evidence suggests that endometriosis patients are at higher risk of
      several chronic diseases. Although the underlying mechanisms are not yet
      understood, the available data to date suggest that endometriosis is not harmless
      with respects to women's long-term health. If these relationships are confirmed,
      these findings may have important implications in screening practices and in the
      management and care of endometriosis patients.

PMID- 25765866
TI  - Effect of enamel bevel on retention of cervical composite resin restorations: A
      systematic review and meta-analysis.
AB  - OBJECTIVES: To identify if enamel bevelling, compared to no treatment, improves
      the retention rates and marginal discolouration of cervical composite
      restorations in non-carious cervical lesions (NCCLs) of adult patients, through a
      systematic review of the literature and meta-analysis. SOURCES: MEDLINE, Scopus,
      Web of Science, LILACS, BBO Library, Cochrane Library and SIGLE were searched
      without restrictions, as well as the abstracts of the annual conference of the
      IADR and the trials registry. Dissertations and theses were searched using the
      ProQuest Dissertations and Periodicos Capes Theses databases. STUDY SELECTION: We
      included randomised clinical trials (RCTs) that compared the retention rates
      restorations in NCCLs placed with or without bevel with at least 1-year follow
      up. The risk of bias tool of the Cochrane Collaboration was used for quality
      assessment. DATA: After duplicate removal, 1356 articles were identified. After
      abstract screening, 14 studies remained and this number was reduced to four after
      examination of the full-texts. Only two were considered to have a 'low' risk of
      bias. The overall risk difference was 0.0 (95% CI -0.04 to 0.04) for the
      retention rate (p=0.91) and 0.05 (-0.02 to 0.13) for the marginal discolouration
      (p=0.17). CONCLUSIONS: No superiority of bevelled restorations was observed in
      the short-term follow-up of 1-year, although this conclusion was based on only
      two RCTs. There is not enough evidence to support the bevelled technique over non
      bevelled for NCCLs over longer periods of time. Better standardization and
      reporting of RCTs of enamel bevelling are necessary in longer-term follow-ups.
      CLINICAL SIGNIFICANCE: The literature still lacks a body of evidence to support
      the benefits of enamel bevel over non-bevelled for longer-term follow-ups, and
      future randomised clinical trials with low risk of bias should be conducted.

PMID- 25765867
TI  - Ten-year clinical outcome of three-unit posterior FDPs made from a glass
      infiltrated zirconia reinforced alumina ceramic (In-Ceram Zirconia).
AB  - OBJECTIVES: To evaluate the long-term survival and complication rates of
      posterior three-unit fixed dental prostheses (FDPs) fabricated from a glass
      infiltrated zirconia reinforced alumina ceramic (In-Ceram Zirconia). METHODS:
      Fifty-eight patients received 65 FDPs. Twelve FDPs replaced the second premolar
      (8 in the maxilla, 4 in the mandible), and 53 replaced the first molar (19 in the
      maxilla, 34 in the mandible). The In-Ceram Zirconia ceramic frameworks were
      designed and milled using the Cerec CAD/CAM system. The minimum dimension of the
      proximal connectors of the frameworks was 12 mm(2) and 16 mm(2) for premolars and
      molars, respectively. After milling and glass infiltration, the frameworks were
      veneered with a feldspathic ceramic. All FDPs were cemented with glass-ionomer
      cement. The patients were recalled 6-12 months after placement, and then
      annually. Kaplan-Meier analysis was used to calculate the survival and
      complication rates of the FDPs. RESULTS: The mean observation time was 9.7 years.
      Six patients with 6 FDPs were regarded as dropouts. Using the Kaplan-Meier method
      the 10-year cumulative survival rate was 93.6%. In a worst-case scenario, in
      which the 6 missing FDPs are considered as failed, the 10-year survival rate
      would be 84.6%. CONCLUSION: Three-unit posterior FDPs made from In-Ceram Zirconia
      presented a 10-year survival rate similar to that reported for conventional FDPs.
      However more technical and biological complications were reported. CLINICAL
      SIGNIFICANCE: Three-unit posterior FDP made from In-Ceram Zirconia may be a
      viable treatment modality, taking the strict adherence to the manufacturer's
      recommendations into consideration.

PMID- 25765868
TI  - Thinking about populations and races in time.
AB  - Biologists and philosophers have offered differing concepts of biological race.
      That is, they have offered different candidates for what a biological correlate
      of race might be; for example, races might be subspecies, clades, lineages,
      ecotypes, or genetic clusters. One thing that is striking about each of these
      proposals is that they all depend on a concept of population. Indeed, some
      authors have explicitly characterized races in terms of populations. However,
      including the concept of population into concepts of race raises three puzzles,
      all having to do with time. In this paper, I extend the causal interactionist
      population concept (CIPC) by introducing some simple assumptions about how to
      understand populations through time. These assumptions help to shed light on the
      three puzzles, and in the process show that if we want to understand races in
      terms of populations, we will need to revise our concept(s) of race. 

PMID- 25765869
TI  - Iatrogenic patellar tendon deficiency treated with rectus femoris tendon turndown
      autograft.

PMID- 25765870
TI  - Loss of alpha-dystroglycan expression in cutaneous melanocytic lesions.

PMID- 25765871
TI  - Second-Line Treatment of Advanced Urothelial Cancer with Paclitaxel and
      Everolimus in a German Phase II Trial (AUO Trial AB 35/09).
AB  - OBJECTIVE: The efficacy of second-line treatment after failure of platinum-based
      chemotherapy in patients with advanced urothelial cancer is limited. Based on
      encouraging preclinical and clinical phase I data, we evaluated the safety and
      efficacy of the combination of paclitaxel and everolimus in these patients.
      METHODS: In this trial, patients having failed to respond to prior platinum-based
      combination treatment of urothelial cancer were treated with paclitaxel (175
      mg/m(2) i.v., 3-weekly) and the mTOR-inhibitor everolimus (10 mg p.o., once
      daily). The patients were treated until tumor progression or until a maximum of 6
      cycles was completed. A one-stage design was used to evaluate the objective
      response rate (ORR) as the primary endpoint. RESULTS: A total of 27 patients (67%
      male; median age 63 years) were enrolled. The most frequent grade III/IV
      toxicities were anemia (28%), peripheral neuropathy (28%), and fatigue (24%). No
      treatment-related deaths were reported. Complete and partial remissions were
      observed in 0/24 and 3/24 patients eligible for efficacy analysis, respectively
      (ORR 13%). Progression-free survival was 2.9 months [95% confidence interval (95%
      CI) 1.9-4.2], and the median overall survival was 5.6 months (95% CI 4.8-10.2).
      CONCLUSION: The combination of paclitaxel and everolimus has not achieved the
      expected efficacy in second-line treatment of urothelial cancer and should not be
      further explored.

PMID- 25765872
TI  - Dose rate estimation of the Tohoku hynobiid salamander, Hynobius lichenatus, in
      Fukushima.
AB  - The radiological risks to the Tohoku hynobiid salamanders (class Amphibia),
      Hynobius lichenatus due to the Fukushima Dai-ichi Nuclear Power Plant accident
      were assessed in Fukushima Prefecture, including evacuation areas. Aquatic egg
      clutches (n = 1 for each sampling date and site; n = 4 in total), overwintering
      larvae (n = 1-5 for each sampling date and site; n = 17 in total), and
      terrestrial juveniles or adults (n = 1 or 3 for each sampling date and site; n =
      12 in total) of H. lichenatus were collected from the end of April 2011 to April
      2013. Environmental media such as litter (n = 1-5 for each sampling date and
      site; n = 30 in total), soil (n = 1-8 for each sampling date and site; n = 31 in
      total), water (n = 1 for each sampling date and site; n = 17 in total), and
      sediment (n = 1 for each sampling date and site; n = 17 in total) were also
      collected. Activity concentrations of (134)Cs + (137)Cs were 1.9-2800, 0.13-320,
      and 0.51-220 kBq (dry kg) (-1) in the litter, soil, and sediment samples,
      respectively, and were 0.31-220 and <0.29-40 kBq (wet kg)(-1) in the adult and
      larval salamanders, respectively. External and internal absorbed dose rates to H.
      lichenatus were calculated from these activity concentration data, using the
      ERICA Assessment Tool methodology. External dose rates were also measured in situ
      with glass dosimeters. There was agreement within a factor of 2 between the
      calculated and measured external dose rates. In the most severely contaminated
      habitat of this salamander, a northern part of Abukuma Mountains, the highest
      total dose rates were estimated to be 50 and 15 MUGy h(-1) for the adults and
      overwintering larvae, respectively. Growth and survival of H. lichenatus was not
      affected at a dose rate of up to 490 MUGy h(-1) in the previous laboratory
      chronic gamma-irradiation experiment, and thus growth and survival of this
      salamander would not be affected, even in the most severely contaminated habitat
      in Fukushima Prefecture. However, further studies of the adult salamanders may be
      required in order to examine whether the most severe radioactive contamination
      has any effects on sensitive endpoints, since the estimated highest dose rate to
      the adults exceeded some of the guidance dose rates proposed by various
      organisations and programmes for the protection of amphibians, which range from 4
      to 400 MUGy h(-1). Conversely, at one site in Nakadori, a moderately contaminated
      region in Fukushima Prefecture, the dose rate to the adult salamanders in spring
      of 2012 was estimated to be 0.2 MUGy h(-1). Estimated dose rates to the
      overwintering larvae in spring of 2012 were 1 and 0.2 MUGy h(-1) at one site in
      Nakadori, and in Aizu, a less contaminated region in Fukushima Prefecture,
      respectively. These results suggest that there is a low risk that H. lichenatus
      will be affected by radioactive contamination in these districts, though further
      studies on dose rate estimation are required for definitive risk
      characterisation.

PMID- 25765873
TI  - Production of a mouse strain with impaired glucose tolerance by systemic
      heterozygous knockout of the glucokinase gene and its feasibility as a
      prediabetes model.
AB  - Exon II of glucokinase (Gk) was deleted to produce a systemic heterozygous Gk
      knockout (Gk(+/-)) mouse. The relative expression levels of Gk in the heart,
      lung, liver, stomach, and pancreas in Gk(+/-) mice ranged from 0.41-0.68 versus
      that in wild (Gk(+/+)) mice. On the other hand, its expression levels in the
      brain, adipose tissue, and muscle ranged from 0.95-1.03, and its expression
      levels in the spleen and kidney were nearly zero. Gk knockout caused no
      remarkable off-target effect on the expression of 7 diabetes causing genes (Shp,
      Hnf1a, Hnf1b, Irs1, Irs2, Kir6.2, and Pdx1) in 10 organs. The glucose tolerance
      test was conducted to determine the blood glucose concentrations just after
      fasting for 24 h (FBG) and at 2 h after high-glucose application (GTT2h). The FBG
      GTT2h plots obtained with the wild strain fed the control diet (CD), Gk(+/-)
      strain fed the CD, and Gk(+/-) strain fed the HFD were distributed in separate
      areas in the FBG-GTT2h diagram. The respective areas could be defined as the
      normal state, prediabetes state, and diabetes state, respectively. Based on the
      results, the criteria for prediabetes could be defined for the Gk(+/-) strain
      developed in this study. 

PMID- 25765874
TI  - Quantitative trait loci on chromosome 5 for susceptibility to frequency-specific
      effects on hearing in DBA/2J mice.
AB  - The DBA/2J strain is a model for early-onset, progressive hearing loss in humans,
      as confirmed in the present study. DBA/2J mice showed progression of hearing loss
      to low-frequency sounds from ultrasonic-frequency sounds and profound hearing
      loss at all frequencies before 7 months of age. It is known that the early-onset
      hearing loss of DBA/2J mice is caused by affects in the ahl (Cdh23(ahl)) and ahl8
      (Fscn2(ahl8)) alleles of the cadherin 23 and fascin 2 genes, respectively.
      Although the strong contributions of the Fscn2(ahl8) allele were detected in
      hearing loss at 8- and 16-kHz stimuli with LOD scores of 5.02 at 8 kHz and 8.84
      at 16 kHz, hearing loss effects were also demonstrated for three new quantitative
      trait loci (QTLs) for the intervals of 50.3-54.5, 64.6-119.9, and 119.9-137.0 Mb,
      respectively, on chromosome 5, with significant LOD scores of 2.80-3.91 for
      specific high-frequency hearing loss at 16 kHz by quantitative trait loci linkage
      mapping using a (DBA/2J * C57BL/6J) F1 * DBA/2J backcross mice. Moreover, we
      showed that the contribution of Fscn2(ahl8) to early-onset hearing loss with 32
      kHz stimuli is extremely low and raised the possibility of effects from the
      Cdh23(ahl) allele and another dominant quantitative trait locus (loci) for
      hearing loss at this ultrasonic frequency. Therefore, our results suggested that
      frequency-specific QTLs control early-onset hearing loss in DBA/2J mice. 

PMID- 25765875
TI  - A simple PCR-based method for the rapid genotyping of inherited fifth complement
      component (C5)-deficient mice.
AB  - The fifth component of complement (C5) is considered to be the center of
      complement activation and function. However, there are no genetically engineered
      knockout mice for this gene, and the only commercially available inherited C5
      deficient mice, in which a "TA" nucleotide deletion in the coding frame was
      previously identified, are in theC57BL/10Sn genetic background rather than the
      commonly used backgrounds C57BL/6 and BALB/c. Therefore, these mice must be
      backcrossed into the desired genetic background. Here, we developed an ARMS
      (amplification refractory mutation system) PCR method using a specific primer
      pair that was able to discriminate between the genotypes when the resulting
      product was analyzed by agarose gel electrophoresis. These results were supported
      by quantitative RT-PCR and semi-quantitative PCR and were consistent with the
      results from sequencing each backcrossed generation. Using ARMS-PCR method, we
      generated C5-deficient mice in the C57BL/6 background over 9 backcrossed
      generations and further verified the phenotype using complement-mediated
      hemolytic assays. In this study, we describe a simple, rapid and reliable PCR
      based method for genotyping inherited C5-deficient mice that may be used to
      backcross C57BL/10Sn mice into other genetic backgrounds. 

PMID- 25765876
TI  - Geriatric assessment-identified deficits in older cancer patients with normal
      performance status.
AB  - BACKGROUND: We investigated whether a brief geriatric assessment (GA) would
      identify important patient deficits that could affect treatment tolerance and
      care outcomes within a sample of older cancer patients rated as functionally
      normal (80%-100%) on the Karnofsky performance status (KPS) scale. METHODS:
      Cancer patients aged >=65 years were assessed using a brief GA that included both
      professionally and patient-scored KPS and measures of comorbidity, polypharmacy,
      cognition, function, nutrition, and psychosocial status. Data were analyzed using
      descriptive statistics and multivariable logistic regression. RESULTS: The sample
      included 984 patients: mean age was 73 years (range: 65-99 years), 74% were
      female, and 89% were white. GA was conducted before (23%), during (41%), or after
      (36%) treatment. Overall, 54% had a breast cancer diagnosis (n = 528), and 46% (n
      = 456) had cancers at other sites. Moreover, 81% of participants (n = 796) had
      both professionally and self-rated KPS >=80, defined as functionally normal, and
      those patients are the focus of analysis. In this subsample, 550 (69%) had at
      least 1 GA-identified deficit, 222 (28%) had 1 deficit, 140 (18%) had 2 deficits,
      and 188 (24%) had >=3 deficits. Specifically, 43% reported taking >=9 medications
      daily, 28% had decreased social activity, 25% had >=4 comorbidities, 23% had >=1
      impairment in instrumental activities of daily living, 18% had a Timed Up and Go
      time >=14 seconds, 18% had >=5% unintentional weight loss, and 12% had a Mental
      Health Index score <=76. CONCLUSION: Within this sample of older cancer patients
      who were rated as functionally normal by KPS, GA identified important deficits
      that could affect treatment tolerance and outcomes.

PMID- 25765878
TI  - Age-stratified risk of unexpected uterine sarcoma following surgery for presumed
      benign leiomyoma.
AB  - BACKGROUND: Estimates of unexpected uterine sarcoma following surgery for
      presumed benign leiomyoma that use age-stratification are lacking. PATIENTS AND
      METHODS: A retrospective cohort of 2,075 patients that had undergone myomectomy
      was evaluated to determine the case incidence of unexpected uterine sarcoma. An
      aggregate risk estimate was generated using a meta-analysis of similar studies
      plus our data. Database-derived age distributions of the incidence rates of
      uterine sarcoma and uterine leiomyoma surgery were used to stratify risk by age.
      RESULTS: Of 2,075 patients in our retrospective cohort, 6 were diagnosed with
      uterine sarcoma. Our meta-analysis revealed 8 studies from 1980 to 2014. Combined
      with our study, 18 cases of leiomyosarcoma are reported in 10,120 patients, for
      an aggregate risk of 1.78 per 1,000 (95% confidence interval [CI]: 1.1-2.8) or 1
      in 562. Eight cases of other uterine sarcomas were reported in 6,889 patients,
      for an aggregate risk of 1.16 per 1,000 (95% CI: 0.5-4.9) or 1 in 861. The
      summation of these risks gives an overall risk of uterine sarcoma of 2.94 per
      1,000 (95% CI: 1.8-4.1) or 1 in 340. After stratification by age, we predict the
      risk of uterine sarcoma to range from a peak of 10.1 cases per 1,000, or 1 in 98,
      for patients aged 75-79 years to <1 case per 500 for patients aged <30 years.
      CONCLUSION: The risk of unexpected uterine sarcoma varies significantly across
      age groups. Our age-stratified predictive model should be incorporated to more
      accurately counsel patients and to assist in providing guidelines for the
      surgical technique for leiomyoma.

PMID- 25765879
TI  - Preparation of a porous conductive scaffold from aniline pentamer-modified
      polyurethane/PCL blend for cardiac tissue engineering.
AB  - A novel biodegradable electroactive polyurethane containing aniline pentamer (AP)
      was blended with polycaprolactone (PCL). The prepared blend (PB) and PCL were
      further fabricated in to scaffolds using a mixture of poly(ethylene glycol) and
      salt particles in a double porogen particulate leaching and compression molding
      methodology. Scaffolds held open and interconnected pores having pore size
      ranging from several MUm to 150 um. PB scaffolds had compression modulus and
      strength of 4.1 and 1.3 MPa, respectively. The conductivity of the scaffold was
      measured as 10(-5) +/- 0.09 S .cm(-1) and preserved for at least 100 h post
      fabrication. Scaffolds supported neonatal cardiomyocytes adhesion and growth with
      PB showing more extensive effect on the expression of the cardiac genes involved
      in muscle contraction and relaxation (troponin-T) and cytoskeleton alignment
      (actinin-4). Our results highlight the potential of incorporation of AP as an
      electroactive moiety for induction of cardiomyocyte proliferation and repair of
      damaged heart tissue.

PMID- 25765880
TI  - A dynamical systems explanation of the Hurst effect and atmospheric low-frequency
      variability.
AB  - The Hurst effect plays an important role in many areas such as physics, climate
      and finance. It describes the anomalous growth of range and constrains the
      behavior and predictability of these systems. The Hurst effect is frequently
      taken to be synonymous with Long-Range Dependence (LRD) and is typically assumed
      to be produced by a stationary stochastic process which has infinite memory.
      However, infinite memory appears to be at odds with the Markovian nature of most
      physical laws while the stationarity assumption lacks robustness. Here we use
      Lorenz's paradigmatic chaotic model to show that regime behavior can also cause
      the Hurst effect. By giving an alternative, parsimonious, explanation using
      nonstationary Markovian dynamics, our results question the common belief that the
      Hurst effect necessarily implies a stationary infinite memory process. We also
      demonstrate that our results can explain atmospheric variability without the
      infinite memory previously thought necessary and are consistent with climate
      model simulations. 

PMID- 25765877
TI  - Platinum-induced neurotoxicity and preventive strategies: past, present, and
      future.
AB  - Neurotoxicity is a burdensome side effect of platinum-based chemotherapy that
      prevents administration of the full efficacious dosage and often leads to
      treatment withdrawal. Peripheral sensory neurotoxicity varies from paresthesia in
      fingers to ataxic gait, which might be transient or irreversible. Because the
      number of patients being treated with these neurotoxic agents is still
      increasing, the need for understanding the pathogenesis of this dramatic side
      effect is critical. Platinum derivatives, such as cisplatin and carboplatin, harm
      mainly peripheral nerves and dorsal root ganglia neurons, possibly because of
      progressive DNA-adduct accumulation and inhibition of DNA repair pathways (e.g.,
      extracellular signal-regulated kinase 1/2, c-Jun N-terminal kinase/stress
      activated protein kinase, and p38 mitogen-activated protein kinass), which
      finally mediate apoptosis. Oxaliplatin, with a completely different
      pharmacokinetic profile, may also alter calcium-sensitive voltage-gated sodium
      channel kinetics through a calcium ion immobilization by oxalate residue as a
      calcium chelator and cause acute neurotoxicity. Polymorphisms in several genes,
      such as voltage-gated sodium channel genes or genes affecting the activity of
      pivotal metal transporters (e.g., organic cation transporters, organic
      cation/carnitine transporters, and some metal transporters, such as the copper
      transporters, and multidrug resistance-associated proteins), can also influence
      drug neurotoxicity and treatment response. However, most pharmacogenetics studies
      need to be elucidated by robust evidence. There are supportive reports about the
      effectiveness of several neuroprotective agents (e.g., vitamin E, glutathione,
      amifostine, xaliproden, and venlafaxine), but dose adjustment and/or drug
      withdrawal seem to be the most frequently used methods in the management of
      platinum-induced peripheral neurotoxicity. To develop alternative options in the
      treatment of platinum-induced neuropathy, studies on in vitro models and
      appropriate trials planning should be integrated into the future design of
      neuroprotective strategies to find the best patient-oriented solution. 

PMID- 25765882
TI  - Electrical conductivity and thermopower of (1 - x) BiFeO(3) - xBi(0.5)K(0.5)TiO3
      (x = 0.1, 0.2) ceramics near the ferroelectric to paraelectric phase transition.
AB  - Ferroelectric BiFeO3 has attractive properties such as high strain and
      polarization, but a wide range of applications of bulk BiFeO3 are hindered due to
      high leakage currents and a high coercive electric field. Here, we report on the
      thermal behaviour of the electrical conductivity and thermopower of BiFeO3
      substituted with 10 and 20 mol% Bi0.5K0.5TiO3. A change from p-type to n-type
      conductivity in these semi-conducting materials was demonstrated by the change in
      the sign of the Seebeck coefficient and the change in the slope of the isothermal
      conductivity versus partial pressure of O. A minimum in the isothermal
      conductivity was observed at ~10(-2) bar O2 partial pressure for both solid
      solutions. The strong dependence of the conductivity on the partial pressure of
      O2 was rationalized by a point defect model describing qualitatively the
      conductivity involving oxidation/reduction of Fe(3+), the dominating oxidation
      state of Fe in stoichiometric BiFeO3. The ferroelectric to paraelectric phase
      transition of 80 and 90 mol% BiFeO3 was observed at 648 +/- 15 and 723 +/- 15 
      degrees C respectively by differential thermal analysis and confirmed by
      dielectric spectroscopy and high temperature powder X-ray diffraction. 

PMID- 25765881
TI  - Between violation and competent care--lived experiences of dependency on care in
      the ICU.
AB  - This study explores the perceived meaning of dependency on care as experienced by
      intensive care patients. Research from non-intensive settings shows that
      dependency is often experienced negatively, but literature on the subject
      experienced by patients in the ICU is sparse. The study is based on in-depth
      qualitative semi-structured interviews of lived experience with three former
      patients admitted to an intensive care unit at a Danish university hospital. The
      in-depth interviews have been characterized as narratives. The main inspiration
      for the analysis method is Ricoeur's phenomenological hermeneutical
      interpretation theory. The study has found that dependency is experienced as
      difficult, and the relationship with the nurses seems to be ambivalent. The good
      relationship is experienced to make dependency easier, whereas negative
      experiences make it harder to cope with dependency. The participants deal with
      dependency by accepting negative experiences in gratitude for having recovered
      from critical illness. The findings might be influenced by studies being
      conducted in a western country setting where independence is valued. They can be
      used as means of reflection on nursing practice and matters such as communication
      and patient participation. 

PMID- 25765883
TI  - Molecular cloning and functional characterization of porcine cyclic GMP-AMP
      synthase.
AB  - Cyclic GMP-AMP synthase (cGAS), which belongs to the nucleotidyltransferase
      family, recognizes cytosolic DNA and induces the type I interferon (IFN) pathway
      through the synthesis of the second messenger cGAMP. In this study, porcine cGAS
      (p-cGAS) was identified and its tissue distribution, subcellular localization,
      and functions in innate immunity were characterized. The coding sequence of p
      cGAS is 1494 bp long, encodes 497 amino acids, and is most similar (74%) to Bos
      taurus cGAS. p-cGAS mRNA is abundant in the spleen, duodenum, jejunum, and ileum.
      The subcellular distribution of p-cGAS is not only in the cytosol, but also on
      the endoplasmic reticulum (ER) membrane. The overexpression of wild-type p-cGAS
      in porcine kidney epithelial cells, but not its catalytically inactive mutants,
      induced IFN-beta expression, which was dependent on STING and IRF3. However, the
      downregulation of p-cGAS by RNA interference markedly reduced IFN-beta expression
      after pseudorabies virus (PRV) infection or poly(dA:dT) transfection. These
      results demonstrate that p-cGAS is an important DNA sensor, required for IFN-beta
      activation.

PMID- 25765884
TI  - Children's bilateral advantage for grasp-to-eat actions becomes unimanual by age
      10 years.
AB  - Studies have shown that infants tend to develop a lateralized hand preference for
      hand-to-mouth actions earlier than they do a preference for many other grasp-to
      place or grasp-to-manipulate tasks, years even before direction of hand
      preference can be reliably determined. This observation has led to a series of
      studies contrasting the kinematics of grasp-to-eat and grasp-to-place actions in
      adults. These studies have described a robust kinematic asymmetry between left-
      and right-handed grasp-to-eat maximum grip apertures (MGAs) that has been
      interpreted as a right-hand advantage for feeding that may have led to right
      handedness as observed on a global scale. The current study examines grasp-to-eat
      and grasp-to-place kinematics in two groups of typically developing children aged
      7 to 12 years. It was found that the previously described task difference is
      present in both hands among younger children and that the effect does not become
      lateralized until the end of the first decade of life. Additional kinematics of
      both the dominant and non-dominant hands are described in detail to augment a
      growing catalogue of reach-to-grasp action descriptions for typically developing
      children. The maturation of the right-hand advantage for grasp-to-eat actions is
      discussed in terms of an inherent right-hand/left-hemisphere bias for such
      actions that may have influenced the development of population-level right
      handedness in humans.

PMID- 25765885
TI  - Bifurcations in a discrete time model composed of Beverton-Holt function and
      Ricker function.
AB  - We provide rigorous analysis for a discrete-time model composed of the Ricker
      function and Beverton-Holt function. This model was proposed by Lewis and Li
      [Bull. Math. Biol. 74 (2012) 2383-2402] in the study of a population in which
      reproduction occurs at a discrete instant of time whereas death and competition
      take place continuously during the season. We show analytically that there exists
      a period-doubling bifurcation curve in the model. The bifurcation curve divides
      the parameter space into the region of stability and the region of instability.
      We demonstrate through numerical bifurcation diagrams that the regions of
      periodic cycles are intermixed with the regions of chaos. We also study the
      global stability of the model. 

PMID- 25765887
TI  - The relationship between hemodialysis modality and insulin resistance in non
      diabetic hemodialysis patients.
AB  - BACKGROUND: Although various modalities of hemodialysis (HD) are presumed to have
      different effects on insulin resistance (IR), the relationship between
      hemodiafiltration (HDF) and IR has not been fully evaluated. METHODS: In a cross
      sectional study, 82 non-diabetic HD patients were enrolled. The patients were
      divided into two groups according to the median homeostasis model assessment
      index (HOMA-IR) value of 1.685. Clinical and biochemical data were compared, and
      multivariate logistic regression analysis was performed to identify the
      independent factors associated with higher HOMA-IR. RESULTS: The higher HOMA-IR
      group had increased body mass index (BMI), decreased HDL cholesterol, and lower
      beta-2 microglobulin reduction rate (beta2-MG RR) compared to the lower HOMA-IR
      group. HOMA-IR was significantly correlated with beta2-MG RR. In addition, HDF
      patients had lower HOMA-IR levels compared with low flux hemodialysis patients.
      On multivariate logistic regression analysis, BMI and HDF treatment were
      independent factors associated with higher and lower HOMA-IR, respectively.
      CONCLUSION: This study suggests that HDF treatment may reduce IR in non-diabetic
      HD patients.

PMID- 25765886
TI  - Mathematical modeling of renal hemodynamics in physiology and pathophysiology.
AB  - In addition to the excretion of metabolic waste and toxin, the kidney plays an
      indispensable role in regulating the balance of water, electrolyte, acid-base,
      and blood pressure. For the kidney to maintain proper functions, hemodynamic
      control is crucial. In this review, we describe representative mathematical
      models that have been developed to better understand the kidney's autoregulatory
      processes. We consider mathematical models that simulate glomerular filtration,
      and renal blood flow regulation by means of the myogenic response and
      tubuloglomerular feedback. We discuss the extent to which these modeling efforts
      have expanded the understanding of renal functions in health and disease. 

PMID- 25765888
TI  - Lipopolysaccharide induces inducible nitric oxide synthase-dependent podocyte
      dysfunction via a hypoxia-inducible factor 1alpha and cell division control
      protein 42 and Ras-related C3 botulinum toxin substrate 1 pathway.
AB  - Urine protein loss in immune complex-mediated diseases such as lupus nephritis is
      associated with podocyte foot process effacement (podocytopathy) but is not
      always dependent on glomerular immune complex deposition. Several murine and
      human studies have associated lupus nephritis with inducible nitric oxide
      synthase (iNOS) expression in what appear to be podocytes. This study was
      conducted to determine mechanisms of immune-complex-independent and iNOS
      dependent podocyte dysfunction. Conditionally immortalized podocytes were
      cultured with lipopolysaccharide (LPS) and nitric oxide (NO), superoxide (SO), or
      peroxynitrite donors in the presence or absence of inhibitors of iNOS, reduced
      nicotinamide adenine dinucleotide phosphate (NADPH) oxidase or monocyte
      chemotactic protein 1 (MCP-1), or with sepiapterin to increase coupling of iNOS
      homodimers. Podocyte NO, SO, and MCP-1 production and nitrotyrosine modifications
      were determined. The podocytopathy phenotype was determined by measuring cell
      motility and membrane permeability to albumin. This study determined that NO
      produced by iNOS is sufficient and necessary to induce podocytopathy. NO probably
      induces this phenotype via hypoxia-inducible factor 1alpha and cell division
      control protein 42 and Ras-related C3 botulinum toxin substrate 1 pathways. With
      LPS stimulation, neither SO nor peroxynitrite produced by uncoupled iNOS or NADPH
      oxidase nor MCP-1 was sufficient to induce the full phenotype. This study
      supports the notion that iNOS may induce autocrine podocyte dysfunction. Thus,
      targeting iNOS or the pathways of its induction may have therapeutic benefit. 

PMID- 25765889
TI  - Laparoscopic versus open obesity surgery: a meta-analysis of pulmonary
      complications.
AB  - The clinical effects of laparoscopy in the pulmonary function of obese patients
      have been poorly investigated in the past. A systematic review was undertaken,
      with the objective to identify published evidence on pulmonary complications in
      laparoscopic surgery in the obese. Outcome measures included pulmonary morbidity,
      pulmonary infection and mortality. The random effects model was used to calculate
      combined overall effect sizes of pooled data. Data are presented as the odds
      ratio (OR) with 95% confidence interval (CI). A total of 6 randomized and 14
      observational studies were included, which reported data on 185,328 patients.
      Pulmonary complications occurred in 1.6% of laparoscopic and in 3.6% of open
      procedures (OR 0.45, 95% CI 0.34-0.60). Pneumonia was reported in 0.5% and in
      1.1%, respectively (OR 0.45, 95% CI 0.40-0.51). Available evidence suggests lower
      pulmonary morbidity for laparoscopic surgery in obese patients; further quality
      studies are however necessary to consolidate these findings.

PMID- 25765890
TI  - Effect of visual cues on the resolution of perceptual ambiguity in Parkinson's
      disease and normal aging.
AB  - Parkinson's disease (PD) and normal aging have been associated with changes in
      visual perception, including reliance on external cues to guide behavior. This
      raises the question of the extent to which these groups use visual cues when
      disambiguating information. Twenty-seven individuals with PD, 23 normal control
      adults (NC), and 20 younger adults (YA) were presented a Necker cube in which one
      face was highlighted by thickening the lines defining the face. The hypothesis
      was that the visual cues would help PD and NC to exert better control over
      bistable perception. There were three conditions, including passive viewing and
      two volitional-control conditions (hold one percept in front; and switch: speed
      up the alternation between the two). In the Hold condition, the cue was either
      consistent or inconsistent with task instructions. Mean dominance durations (time
      spent on each percept) under passive viewing were comparable in PD and NC, and
      shorter in YA. PD and YA increased dominance durations in the Hold cue-consistent
      condition relative to NC, meaning that appropriate cues helped PD but not NC hold
      one perceptual interpretation. By contrast, in the Switch condition, NC and YA
      decreased dominance durations relative to PD, meaning that the use of cues helped
      NC but not PD in expediting the switch between percepts. Provision of low-level
      cues has effects on volitional control in PD that are different from in normal
      aging, and only under task-specific conditions does the use of such cues
      facilitate the resolution of perceptual ambiguity.

PMID- 25765892
TI  - The effect of quercetin and kaempferol aglycones and glucuronides on peroxisome
      proliferator-activated receptor-gamma (PPAR-gamma).
AB  - The consumption of dietary flavonoids has been associated with a variety of
      health benefits, including effects mediated by the activation of peroxisome
      proliferator-activated receptor-gamma (PPAR-gamma). Flavonoids are extensively
      metabolized during and after uptake and there is little known on the biological
      effects of these conjugated metabolites of flavonoids that are found in plasma.
      To investigate the effect of glucuronidation on the ability of flavonoids to
      activate PPAR-gamma we studied and compared the activity of quercetin, kaempferol
      and their relevant plasma conjugates quercetin-3-O-glucuronide (Q3G) and
      kaempferol-3-O-glucuronide (K3G) on different PPAR-gamma related endpoints. The
      flavonoid aglycones increased PPAR-gamma mediated gene expression in a stably
      transfected reporter gene cell line and glucuronidation diminished their effect.
      To study the intrinsic activity of the test compounds to activate PPAR-gamma we
      used a novel microarray technique to study ligand induced ligand binding domain
      (LBD) - nuclear receptor coregulator interactions. In this cell-free system we
      demonstrate that, unlike the known PPAR-gamma agonist rosiglitazone, neither the
      flavonoid aglycones nor the conjugates are agonistic ligands of the receptor. The
      increases in reporter gene expression in the reporter cells were accompanied by
      increased PPAR-gamma receptor-mRNA expression and quercetin synergistically
      increased the effect of rosiglitazone in the reporter gene assay. It is concluded
      that flavonoids affect PPAR-gamma mediated gene transcription by a mode of action
      different from agonist binding. Increases in PPAR-gamma receptor mRNA expression
      and synergistic effects with endogenous PPAR-gamma agonists may play a role in
      this alternative mode of action. Glucuronidation reduced the activity of the
      flavonoid aglycones. 

PMID- 25765891
TI  - The distribution and mutagenesis of short coding INDELs from 1,128 whole exomes.
AB  - BACKGROUND: Identifying insertion/deletion polymorphisms (INDELs) with high
      confidence has been intrinsically challenging in short-read sequencing data. Here
      we report our approach for improving INDEL calling accuracy by using a machine
      learning algorithm to combine call sets generated with three independent methods,
      and by leveraging the strengths of each individual pipeline. Utilizing this
      approach, we generated a consensus exome INDEL call set from a large dataset
      generated by the 1000 Genomes Project (1000G), maximizing both the sensitivity
      and the specificity of the calls. RESULTS: This consensus exome INDEL call set
      features 7,210 INDELs, from 1,128 individuals across 13 populations included in
      the 1000 Genomes Phase 1 dataset, with a false discovery rate (FDR) of about
      7.0%. CONCLUSIONS: In our study we further characterize the patterns and
      distributions of these exonic INDELs with respect to density, allele length, and
      site frequency spectrum, as well as the potential mutagenic mechanisms of coding
      INDELs in humans.

PMID- 25765893
TI  - Partner support and anxiety in young women with breast cancer.
AB  - OBJECTIVE: Using a large prospective cohort of women age 40 or younger diagnosed
      with breast cancer, we examined the relationship between perceived partner
      support and anxiety. METHODS: Six hundred seventy-five young women with breast
      cancer Stages I-III, median age 36, completed a self-report baseline
      questionnaire. Perceived partner support was assessed using items extracted from
      the marital subscale of the Cancer Rehabilitation Evaluation System; generalized
      social support was assessed with the Medical Outcomes Study-Social Support
      Survey. Anxiety was measured using the anxiety subscale of the Hospital Anxiety
      and Depression Scale. Multivariable logistic regression analyses evaluated the
      association between partner support, other sociodemographic factors, and anxiety.
      RESULTS: Mean age at diagnosis was 35.4 years. Fourteen percent of the women were
      not partnered, and among those who were partnered or in a significant
      relationship, 20% were categorized as unsupported. In univariate and
      multivariable analysis adjusting for sociodemographic factors, women in an
      unsupported-partnered relationship had higher odds of anxiety symptoms compared
      with women in a supported-partnered relationship. Young age and being financially
      insecure were also both independently associated with anxiety. CONCLUSIONS: Our
      findings suggest that partner support may play a key role in a young woman's
      adjustment to a serious stressor such as breast cancer. In addition, younger age
      increases vulnerability to anxiety as does struggling with finances. Because
      supportive efforts of a partner have potential to protect against the impact of
      stress, interventions to enhance partner support and reduce anxiety might be
      beneficial to address challenges experienced as a couple in this setting.

PMID- 25765894
TI  - Identification of a novel large CYP17A1 deletion by MLPA analysis in a family
      with classic 17alpha-hydroxylase deficiency.
AB  - Steroid 17alpha-hydroxylase deficiency (17OHD) is a rare form of congenital
      adrenal hyperplasia caused by mutations in the 17alpha-hydroxylase ( CYP17A1)
      gene. CYP17A1 is a key enzyme in the biosynthesis of adrenal and gonadal steroid
      hormones facilitating both 17alpha-hydroxylase and 17,20-lyase activities. We
      characterized a partial CYP17A1 deletion in a Kurdish family with 17OHD by
      multiplex ligation-dependent probe amplification (MLPA). The index patient
      presented with amenorrhea and lack of pubertal development. Investigations
      established the diagnosis of 46,XY disorder of sex development (DSD). She is the
      daughter of consanguineous parents and has 2 sisters with similar clinical
      presentation. All patients showed biochemical signs of primary adrenal and
      gonadal insufficiency. The molecular genetic analysis by PCR suggested a deletion
      spanning exons 1-6 of the CYP17A1 gene. MLPA analysis confirmed the large partial
      CYP17A1 deletion in patients and parents in homozygous and heterozygous state,
      respectively. This is the first report employing MLPA for mutation analysis to
      detect a deletion of CYP17A1 spanning multiple exons in 3 patients with classic
      17OHD. Therefore, it is important to consider large partial CYP17A1 deletions in
      17OHD in addition to point mutations in cases where no segregation analysis is
      possible to determine the correct genotype.

PMID- 25765895
TI  - The role of apparent diffusion coefficient values in detecting testicular
      intraepithelial neoplasia: preliminary results.
AB  - INTRODUCTION: The aim of this study is to improve detection of testicular
      intraepithelial neoplasia (TIN) by measurement of apparent diffusion coefficient
      (ADC) values. MATERIALS AND METHODS: Fifty-six MRI examinations of the scrotum,
      including 26 histologically proven testicular germ cell neoplasms were
      retrospectively evaluated. DWI was performed using a single shot, multi-slice
      spin-echo planar diffusion pulse sequence and b-values of 0 and 900 s mm(-2). ADC
      measurements were classified into three groups according to their location: group
      1 (n=19), non-tumoral part, adjacent to testicular carcinoma, where the possible
      location of TIN was; group 2 (n=26), testicular carcinoma; and group 3 (n=60),
      normal testicular parenchyma. Analysis of variance (ANOVA) followed by post hoc
      analysis (Dunnett T3) was used for statistical purposes. RESULTS: The mean+/-s.d.
      of ADC values (*10(-3) mm(2)/s) of different groups were: group 1, 1.08+/-0.20;
      group 2, 0.72+/-0.27; and group 3, 1.11+/-0.14. ANOVA revealed differences of
      mean ADC between groups (F=38.859, P<0.001). Post hoc analysis showed differences
      between groups 2 and 3 (P<0.001), groups 2 and 1 (P<0.001), but not between
      groups 3 and 1 (P=0.87). CONCLUSIONS: Based on our preliminary results, ADC
      values do not provide a reliable differentiation between TIN and testicular
      carcinoma or normal testicular parenchyma.

PMID- 25765896
TI  - Anatomical variation of thyroid veins on contrast-enhanced multi-detector row
      computed tomography.
AB  - OBJECTIVE: The objective of this study was to clarify the anatomical variation of
      thyroid veins into the systemic vein using contrast-enhanced multi-detector row
      computed tomography (MDCT). DESIGN AND METHODS: The subjects were 80 patients (34
      males and 46 females; mean age, 50.1 years; age range, 15-92 years) with neck
      diseases who underwent MDCT. The number and location of inflow points of the
      thyroid veins into the systemic vein, and the length from the junction of
      bilateral brachiocephalic veins to the orifice of inferior thyroid vein were
      investigated by reviewing the axial and coronal images. RESULTS: All superior
      thyroid veins were detected. Right and left middle thyroid veins were identified
      in 39 and 29 patients, respectively. Right inferior thyroid veins, left inferior
      thyroid veins, and common trunks were detected in 43, 46, and 39 patients,
      respectively; in five patients, two left thyroid veins were identified. All left
      inferior thyroid veins and 34 common trunks flowed into the innominate vein,
      while right ones had some variations in inflow sites. Mean lengths were 3.01+/
      1.30 cm (range, 0.5-6.19) and 2.04+/-0.91 cm (0.5-4.4) in the left inferior
      thyroid vein and common trunk, and 1.96+/-1.05 cm (0.81-4.8) and 1.65+/-0.69 cm
      (0.63-2.94) in the right one flowing into the right internal jugular vein and the
      innominate vein, respectively. CONCLUSIONS: The numbers and orifices of thyroid
      veins were identified at high rates on contrast-enhanced MDCT. This strategy can
      provide anatomical information before selective venous sampling for measurements
      of parathyroid hormone.

PMID- 25765897
TI  - Selective loss of oxytocin and vasopressin in the hypothalamus in early
      Huntington disease: a case study.

PMID- 25765898
TI  - Comparison of endoscopic balloon dilation with metal stent placement in the
      treatment of achalasia.
AB  - OBJECTIVE: To compare the outcomes of endoscopic balloon dilation and metal stent
      placement in patients with achalasia. METHODS: The patients with newly diagnosed
      achalasia between July 2001 and December 2011 were retrospectively studied. A
      total of 88 patients underwent either balloon dilation (n = 41) or metal stent
      placement (n = 47), their global symptom score and esophageal kinetics index were
      determined before, one week after and one month after the treatment. All the
      patients were followed up in the Outpatient Clinics or with a telephone interview
      every 6 months. RESULTS: There were significant improvements in the global
      symptom scores and esophageal kinetics indices in all patients. No major
      complications were encountered in either group. There were no significant
      differences with regard to overall treatment failure or long-term outcome.
      CONCLUSION: Balloon dilation and removable stents can effectively relieve
      clinical manifestations in patients with achalasia.

PMID- 25765899
TI  - Impact of nutritional status on the pharmacokinetics of erlotinib in rats.
AB  - Malnourishment is a complex condition in which physiopathological changes take
      place in multiple systems as a result of energy, protein and nutrient deficiency.
      The purpose of this study was to evaluate, using an experimental animal model,
      the impact of nutritional status on the pharmacokinetic profile of erlotinib, a
      reversible, highly selective, human epidermal growth factor receptor (HER1/EGFR)
      tyrosine kinase inhibitor. Two groups of rats -WN (well-nourished) and UN
      (undernourished) - were fed with different diets for 23-26 days. Rats were
      assigned randomly to one of three erlotinib treatments (n = 42) consisting of a
      single dose administered intravenously (i.v.), via oral solution or via oral
      suspension. Blood samples were assayed for erlotinib concentration. A population
      pharmacokinetic model was developed and pharmacokinetic parameters obtained in UN
      rats were compared with those in WN rats. Erlotinib clearance suffered a 5%
      decrease in the mild-undernutrition status. Moreover, when the drug was
      administered orally as a suspension, the extent and rate of absorption underwent
      a 20% increase in UN rats. The results of this study might help to explain, at
      least in part, the variability of erlotinib treatment and could represent the
      first step towards establishing new dosage guidelines for the treatment of
      undernourished cancer patients. Copyright (c) 2015 John Wiley & Sons, Ltd.

PMID- 25765900
TI  - (99m) Tc radiolabeling and biological evaluation of nanoparticles functionalized
      with a versatile coating ligand.
AB  - Radiolabeling allows noninvasive imaging by single photon emission computed
      tomography (SPECT) or positron emission tomography (PET) for assessing the
      biodistribution of nanostructures. Herein, the synthesis of a new coating ligand
      for gold nanoparticles (AuNPs) and quantum dots (QDs) is reported. This ligand is
      multifunctional; it combines the metal chelate with conjugating functions to
      biological vectors. The concept allows the coupling of any targeting function to
      the chelator; an example for the prostate specific membrane antigen is given.
      Derivatized NPs can directly be labeled in one step with [(99m) Tc(OH2 )3 (CO)3
      ](+) . AuNPs in particular are highly stable, a prerequisite for in vivo studies
      excluding misinterpretation of the biodistribution data. AuNPs with differing
      sizes (7 and 14 nm core diameter) were administered intravenously into nude NMRI
      mice bearing LNCaP xenografts. MicroSPECT images show for both probes rapid
      clearance from the blood pool through the hepatobiliary pathway. The 7 nm AuNPs
      revealed a significantly higher bone uptake than the 14 nm AuNPs. The high
      affinity towards bone mineral is further confirmed in vitro with hydroxyapatite. 

PMID- 25765901
TI  - Reciprocal repression between TUSC7 and miR-23b in gastric cancer.
AB  - Recently, long noncoding RNAs (lncRNAs) were demonstrated to play important
      regulatory roles in biological processes and cancer biology. However, the overall
      pathophysiological contribution of lncRNAs to gastric cancer (GC) remains largely
      unknown. In this study, differentially expressed lncRNAs in GC and paired
      adjacent normal tissue samples were identified by microarray and were validated
      using quantitative real-time polymerase chain reaction (qRT-PCR). One particular
      lncRNA, tumour suppressor candidate 7 (TUSC7), was analyzed in sequential large
      cohorts, and the Kaplan-Meier method with the log-rank test for comparisons was
      used to analyse the survival data. The results indicated that TUSC7 was
      downregulated in GC samples and was an independent prognostic indicator of
      disease-free survival (DFS) and disease-specific survival (DSS) in GC patients.
      Applying loss-of-function and gain-of-function approaches, we determined that
      TUSC7 suppressed tumour cell growth in vitro and in vivo. Furthermore, we showed
      that TUSC7 was a direct transcriptional target of p53 via interaction of p53 with
      the putative p53-response element in the upstream region of TUSC7. Finally, we
      demonstrated reciprocal repression between TUSC7 and miR-23b; in contrast to
      TUSC7, miR-23b promoted cell growth. The results indicated that TUSC7 is a p53
      regulated tumour suppressor that acts in part by repressing miR-23b and that
      TUSC7 may be a key regulatory hub in GC. 

PMID- 25765902
TI  - Clinicopathologic features of IgA-dominant infection-associated
      glomerulonephritis: a pooled analysis of 78 cases.
AB  - BACKGROUNDS: IgA-dominant infection-associated glomerulonephritis (IgA-dominant
      IAGN) is a unique form of glomerulonephritis. There are numerous case reports in
      the literature. However, the risk factors, treatment approach, and outcomes of
      the disease are not clearly characterized. METHODS: We completed a pooled
      analysis based on published literature. Clinical features, laboratory findings,
      and histopathological changes were analyzed. A logistic regression model was
      employed to identify the determinants of disease outcome, for example, end-stage
      renal disease (ESRD) or death. RESULTS: Seventy-eight patients with IgA-dominant
      IAGN from 28 reports were analyzed. All of these patients showed granular IgA
      deposits predominantly along the glomerular peripheral capillary walls using
      immunofluorescence and majority showed subepithelial 'hump-shaped' electron-dense
      deposits using electron microscopy. The majority of patients had hematuria
      (76/78), proteinuria (75/78), acute kidney injury (AKI) (66/78) and
      hypocomplementemia (43/75) without a previous history of renal disease. All of
      the patients had clinical infections at the time of presentation. Skin infections
      (19/78) and visceral abscesses (15/78) were frequently encountered, and
      staphylococcus was the most common pathogen. After treatment with antibiotics
      and/or supportive therapy, the renal function of 42 patients (54.5%) improved, 9
      patients (11.7%) had persistent renal dysfunction, 15 patients (19.5%) progressed
      to ESRD, and 11 patients (14.3%) died. A multivariate regression analysis
      revealed that age (odds ratio [OR], 30.71; 95% confidence interval [CI], 2.53
      373.07; p = 0.007) and diabetes mellitus (DM) (OR, 16.65; 95% CI, 1.18-235.84; p
      = 0.038) were independent risk factors for ESRD or death. CONCLUSIONS: IgA
      dominant IAGN has unique clinicopathological manifestations and treatment
      responses. Age and DM are independent risk factors associated with an unfavorable
      prognosis for IgA-dominant IAGN.

PMID- 25765903
TI  - Sutureless aortic valve replacement for aortic incompetence.
AB  - OBJECTIVE: Sutureless prostheses for surgical aortic valve replacement (AVR) are
      usually used in degenerative calcified aortic stenosis. Less is known on the
      application of sutureless prostheses for pure aortic incompetence. METHODS:
      Between 2011 and 2014, 442 patients were operated on with the Perceval aortic
      sutureless valve implant. We identified 11 patients (10 female, mean age 70.5)
      who underwent sutureless AVR for pure aortic incompetence (off-label use). Three
      patients had a left ventricle ejection fraction of 30% or less. Mean logistic
      EuroSCORE was 15.2 (range 2.2-45.2). In five patients associated mitral
      procedures (three [60%] repair and two [40%] replacement) were performed. Four
      procedures were performed through a minimally invasive approach (three right
      minithoracotomies and one partial sternotomy). RESULTS: Mean cardiopulmonary
      bypass time was 130.2 min and aortic cross clamp time was 82.2 min. Mean
      implanted prosthesis size was 24.5 +/- 1.3 (median 25) mm (insignificant
      correlation with preoperative aortic valve annulus measurement by transthoracic
      echocardiography: 21.6 +/- 1.5 [median 21] mm, Pearson's r = 0.373, p = 0.259).
      One patient died on 24th day after AVR associated with aortic arch replacement
      and hypothermic circulatory arrest (10 years after correction for type A aortic
      dissection). No residual para- or intravalvular leakage was present on discharge
      and 12-month follow-up. No migration of the prosthesis occurred. CONCLUSION:
      Sutureless AVR is an option in selected patients with aortic incompetence.
      Preoperative aortic annulus measurement by echocardiography has poor predictive
      value for estimation of prosthetic valve size.

PMID- 25765904
TI  - MR imaging of the developing brain. Introduction.

PMID- 25765906
TI  - Indirubin 3'-(O-oxiran-2-ylmethyl)oxime: a novel anticancer agent.
AB  - Indirubin is a potent inhibitor of cell cycle-related protein kinases by binding
      to the ATP-binding site and thus is a promising compound for development as an
      antitumor drug. We prepared indirubin 3'-(O-oxiran-2-ylmethyl)oxime (Epox/Ind),
      in which the ATP-binding site orientated part was attached by non-specific
      alkylating group. The IC50 value of Epox/Ind at 1.7 MUM in HepG2 cells is
      comparable to that of cisplatin (4.0 MUM). Furthermore, Epox/Ind was shown to be
      metabolized by a HepG2 cell lysate into indirubin 3'-(O-2,3-dihydroxypropyl)oxime
      (E804), the sole extractable metabolite. The lower toxicity of this metabolite
      may explain the lack of cytotoxicity of 1 MUM Epox/Ind observed in HepG2 cells
      beyond an initial loss of viability in the first 24h of treatment.

PMID- 25765907
TI  - Synthesis, in vitro anticancer and antimycobacterial evaluation of new 5-(2,5
      dimethoxyphenyl)-1,3,4-thiadiazole-2-amino derivatives.
AB  - A series of 2,5-disubstituted-1,3,4-thiadiazole derivatives 5a-5l, 7a-7e and 9
      have been synthesised and screened for in vitro antimycobacterial activity
      against Mycobacterium smegmatis MC-155. In addition these compounds have also
      been screened for cytotoxic activity against cancer cell lines HT-29, MDA-MB-231
      by MTT colorimetric assay. The compounds are well characterized by spectral
      analysis viz. (1)H NMR, (13)C NMR, FT-IR, mass and HRMS. Screening results
      indicate that compounds 5g, 7a possess good antitubercular activity with MIC
      value 65.74 and 40.86, respectively, compounds 5g, 7a, 7b, 7d, 7e and 9 displayed
      promising cytotoxic activity against the cell lines tested. 5g and 7a stand out
      to be potent antimycobacterial and anticancer agents among the tested series.
      Further the title compounds were also tested on human normal cells HEK293T and
      are found to be safer with lesser cytotoxicity. It is interesting to observe that
      compound 5g has come out to be safer, potent anticancer and antimycobacterial
      agent. 

PMID- 25765908
TI  - The zinc coordination pattern in the eta-carbonic anhydrase from Plasmodium
      falciparum is different from all other carbonic anhydrase genetic families.
AB  - In this Letter we reinvestigate the sequence analysis and report a homology model
      of the carbonic anhydrase (CA, EC 4.2.1.1) from the protozoan parasite Plasmodium
      falciparum, recently reported by us to belong to a new genetic family, the eta-CA
      class. Our findings show that the metal ion coordination pattern of this CA is
      unique among all five other genetic families encoding for such enzymes,
      comprising two His and one Gln residues, in addition to the water
      molecule/hydroxide ion acting as nucleophile in the catalytic cycle. Although the
      eta- and alpha-CAs present the same 3D fold, strongly suggesting the first ones
      to be evolutionary derived from the last, there are significant differences
      between the two families to allow optimism for the drug design of selective
      inhibitors for the parasite over the host enzymes. The preliminary studies
      reported here are relevant for drug design campaigns of anti-plasmodium CA
      inhibitors but further work by X-ray crystallography should validate the proposed
      model. 

PMID- 25765905
TI  - Advanced MR imaging of the placenta: Exploring the in utero placenta-brain
      connection.
AB  - The placenta is a vital organ necessary for the healthy neurodevelopment of the
      fetus. Despite the known associations between placental dysfunction and
      neurologic impairment, there is a paucity of tools available to reliably assess
      in vivo placental health and function. Existing clinical tools for placental
      assessment remain insensitive in predicting and evaluating placental well-being.
      Advanced MRI techniques hold significant promise for the dynamic, non-invasive,
      real-time assessment of placental health and identification of early placental
      based disorders. In this review, we summarize the available clinical tools for
      placental assessment, including ultrasound, Doppler, and conventional MRI. We
      then explore the emerging role of advanced placental MR imaging techniques for
      supporting the developing fetus and appraise the strengths and limitations of
      quantitative MRI in identifying early markers of placental dysfunction for
      improved pregnancy monitoring and fetal outcomes.

PMID- 25765909
TI  - Design, synthesis and antiproliferative activity evaluation of m-(4-morpholinyl
      1,3,5-triazin-2-yl)benzamides in vitro.
AB  - In the present study, a series of m-(4-morpholino-1,3,5-triazin-2-yl)benzamides
      were designed, synthesized and characterized. Their antiproliferative activities
      against HCT-116 cell and MCF-7 cell at 10MUM were evaluated by MTT assay.
      Compounds T6, T10, T11, T12 and T19 exhibited potent antiproliferative
      activities. Thus, their IC50 values against HCT-116 cell, MCF-7 cell, Hela cell,
      U-87 MG cell and A549 cell were measured. The SAR of the target compounds was
      preliminary discussed. The Western bolt assay suggested that compound T11 can
      block the PI3K/Akt/mTOR pathway. Hoechst staining assay indicated that compound
      T11 can cause morphological changes and induce apoptosis of HCT-116 cells. These
      findings directly identify the m-(4-morpholinyl-1,3,5-triazin-2-yl)benzamide
      derivatives as novel antiproliferative agents and further verify the value of the
      benzamide fragment in drug design. 

PMID- 25765910
TI  - Rapid 'one-pot' synthesis of a novel benzimidazole-5-carboxylate and its
      hydrazone derivatives as potential anti-inflammatory and antimicrobial agents.
AB  - A novel series of N-arylidene-2-(2,4-dichloro phenyl)-1-propyl-1H-benzo[d]
      imidazole-5-carbohydrazides having different substitution on the arylidene part
      were synthesized in good yield. The core nucleus benzimidazole-5-carboxylate (5)
      was efficiently synthesized by 'one-pot' nitro reductive cyclization reaction
      between ethyl-3-nitro-4-(propylamino)benzoate and 2,4-dichlorobenzaldehyde using
      sodium dithionite in dimethylsulfoxide. This 'one-pot' reaction was proceeded
      very smoothly, in short reaction time with an excellent yield. All the compounds
      (7a-r) were screened for their in vivo anti-inflammatory and in vitro
      antimicrobial activity. Most of the compounds exhibited remarkable paw-edema
      inhibition in the initial one hour of administration indicating the higher
      potentiality of these molecules. In particular, compounds 7a, 7d, 7f and 7g
      displayed a high level of carrageenan-induced paw edema inhibition compared to
      that of indomethacin. Compound 7p exhibited very good antibacterial activity and
      antifungal activity with a MIC of 3.12 MUg/mL against most of the tested
      organisms. Furthermore, compounds 7d, 7f, 7h and 7p found to be good inhibitors
      of Aspergillus niger with MIC of 3.12 MUg/mL. Cytotoxicity of the potent
      compounds 7d, 7f and 7p was checked using MDA MB-231 breast cancer cell line and
      are found to be non toxic at the highest concentration used (i.e., 10 MUg/mL).

PMID- 25765911
TI  - Synthesis and biological evaluation of isoxazoline derivatives as potent M1
      muscarinic acetylcholine receptor agonists.
AB  - A series of azacyclic compounds substituted with isoxazole and 5-substituted
      isoxazolines were synthesized as acyclic modifications of the oxime class M1 mACh
      receptor agonist. Among them, 3-(tetrahydropyrin-3-yl)-5-(2-pyrrolodin-1
      yl)isoxazoline compound 4f displayed potent and selective M1 mACh receptor
      agonist activity in the functional calcium mobilization assay (EC50=31 nM).
      Introduction of 2-pyrrolidinone and 3-tetrahydropyridine groups are pivotal to
      the high potency. Moreover, 4f was found to facilitate non-amyloidogenic amyloid
      precursor protein (APP) processing by significantly increasing ERK1/2
      phosphorylation and sAPPalpha secretion, known disease-modifying effects related
      to M1 mAChR agonists in Alzheimer's disease (AD).

PMID- 25765912
TI  - Synthesis of a chondroitin sulfate disaccharide library and a GAG-binding protein
      interaction analysis.
AB  - Chondroitin sulfate (CS), which belongs to the glycosaminoglycan (GAG)
      superfamily, is a linear sulfated polysaccharide involved in various biological
      processes. CS structure is very heterogeneous and contains various sulfation
      patterns owing to the multiple and random enzymatic modifications that occur
      during its biosynthesis. The resultant microdomain structure in the CS chain
      interacts with specific biomolecules to regulate biological functions. Therefore,
      an analysis of the structure-activity relationship of CS at the molecular level
      is necessary to clarify their biofunctions. In this study, we designed the common
      intermediate possessing an orthogonally removable protective group and
      systematically synthesized all 16 types of CS disaccharide structure generated by
      sulfation. In addition, we demonstrated the on-time analysis of the binding
      properties of GAG-binding proteins using 'Sugar Chip' immobilized CS disaccharide
      structures by surface plasmon resonance (SPR) imaging, indicating that our chip
      technology is effective for the evaluation of binding properties. 

PMID- 25765914
TI  - Solution-Based Synthesis of Layered Intergrowth Compounds of the Homologous Pbm
      Bi2n Te3n+m Series as Nanosheets.
AB  - Layered intergrowth compounds in the homologous Pbm Bi2n Te3n+m family are
      interesting because they are examples of natural heterostructures. We present a
      simple solution-based synthesis of two-dimensional nanosheets of PbBi2 Te4 , Pb2
      Bi2 Te5 , and PbBi6 Te10 layered intergrowth compounds, which are members of the
      Pbm Bi2n Te3n+m [that is, (PbTe)m (Bi2 Te3 )n ] homologous series. Few-layer
      nanosheets exhibit narrow optical band gaps (0.25-0.7 eV) with semiconducting
      electronic-transport properties.

PMID- 25765913
TI  - Progression to regular heroin use: examination of patterns, predictors, and
      consequences.
AB  - BACKGROUND: The present study retrospectively evaluated the chronology and
      predictors of substance use progression in current heroin-using individuals.
      METHODS: Out-of-treatment heroin users (urinalysis-verified; N=562) were screened
      for laboratory-based research studies using questionnaires and urinalysis.
      Comprehensive substance use histories were collected. Between- and within
      substance use progression was analyzed using stepwise linear regression models.
      RESULTS: The strongest predictor of onset of regular heroin use was age at
      initial heroin use, accounting for 71.8% of variance. The strongest between
      substance predictors of regular heroin use were ages at regular alcohol and
      tobacco use, accounting for 8.1% of variance. Earlier onset of regular heroin use
      (<=20 years) vs. older onset (>=30 years) was associated with a more rapid
      progression from initial to regular use, longer duration of heroin use, more
      lifetime use-related negative consequences, and greater likelihood of injecting
      heroin. The majority of participants (79.7%) reported substance use progression
      consistent with the gateway hypothesis. Gateway-inconsistent individuals were
      more likely to be African-American and to report younger age at initial use,
      longer duration of heroin use, and more frequent past-month heroin use.
      CONCLUSIONS: Our findings demonstrate the predictive validity and clinical
      relevance of evaluating substance use chronology and the gateway hypothesis
      pattern of progression.

PMID- 25765915
TI  - Heparin resistance and coagulation activation rebound effect after anticoagulant
      withdrawal: beneficiary effect of adjuvant antiplatelet therapy.
AB  - BACKGROUND: Aim. The aim of this study was to investigate biological resistance
      to enoxaparin and rebound effect after prophylaxis withdrawal, using thrombin
      generation (TG) assay. METHODS: Fifteen-patients undergoing femoro-popliteal
      bypass grafting (enoxaparin 4000 antiXaIU+75 mg clopidogrel), and 15-patients
      undergoing total-hip-replacement (THR) (enoxaparin alone). TG-assay parameters
      (lag-time, endogenous-thrombin-potential, peak-, time-to-peak, and Mean-Rate
      Index) were assessed to investigate heparin resistance and rebound effect after
      prophylaxis interruption. Measurements were obtained preoperative, postoperative
      (before prophylaxis initiation), 8-days postoperative, and 48-hours after
      anticoagulant withdrawal (day 32). RESULTS: Surgery increased TG in vascular
      patients despite intra-operative unfractioned heparin administration when
      compared to orthopedic patients (MRI:P=0.039, ETP:P=0.001, PGT:P=0.003), but this
      perioperative prothrombotic status was reversed by postoperative
      thromboprophylaxis. No thromboembolic events were observed. Similar TG parameter
      values between the 8th and 32nd postoperative day indicate that vascular patients
      were adequately protected after prophylaxis withdrawal, probably due to the
      synergic action of clopidogrel, while orthopedic patients increased TG on day-32
      compared to the 8th postoperative day (P=0.03, for both lag-time and ttPeak).
      Furthermore, on day-32, a prothrombotic status (increased TG) was observed in the
      orthopedic patients (P=0.034, and 0.004 for ttPeak and lag-time, respectively).
      Inter-individual variability to enoxaparin response was observed in both
      groups:7/15 vascular and 10/15 orthopedic patients increased TG despite
      anticoagulant administration, which reveals heparin-resistance. Among the heparin
      resistant patients, 4 vascular and 6 orthopedic increased TG after anticoagulant
      withdrawal, depicting a rebound effect to activation of coagulation. CONCLUSIONS:
      Heparin-resistance is not a rare phenomenon in clinical practice and was found in
      about half of our patients. A rebound effect of coagulation activation after
      thromboprophylaxis withdrawal is observed in the extended postoperative period.
      This phenomenon is attenuated with the addition of concomitant antiplatelet
      (clopidogrel) treatment.

PMID- 25765916
TI  - Burden of Behavioral and Psychiatric Symptoms in People Screened Positive for
      Dementia in Primary Care: Results of the DelpHi-Study.
AB  - BACKGROUND: There is limited knowledge about the range and effects of
      neuropsychiatric symptoms shown by persons with dementia (PWD) living in the
      community and their related caregiver burden. OBJECTIVE: To examine
      neuropsychiatric symptoms in PWD in primary care with regard to frequency,
      severity, and burden to caregiver; to compare PWD with and without symptoms with
      regard to sociodemographics, care-related, and disease-related variables; and to
      identify variables associated with symptoms. METHODS: A general physician-based
      epidemiological cohort of 248 people screened positive for dementia over the age
      of 70 (living at home) and their caregivers, was assessed using the
      Neuropsychiatric Interview (NPI), sociodemographics, and disease-related
      variables. RESULTS: In preliminary analyses, neuropsychiatric symptoms were
      frequent in PWD. Prevalence numbers ofdysphoria/depression, apathy, and
      agitation/aggression were each more than 30% . The severity of neuropsychiatric
      symptoms in people screened positive for dementia in primary care is moderate
      with a mean NPI score of m = 11.91 (SD = 16.0). Overall, caregiver distress is
      low, indicated by a total distress score of m = 5.94 (SD = 7.2, range 0-39).
      Common or frequent symptoms are not necessarily the most distressing symptoms.
      CONCLUSIONS: Neuropsychiatric symptoms are common in people screened positive for
      dementia in primary care. While frequency, severity, and perceived distress might
      be low in the total sample, we identified the dimensions delusions, aggression,
      anxiety, disinhibition, and depression to be perceived "severely" to "extremely"
      distressing in more than 30% of the caregivers affected. The association between
      activities of daily living and symptoms needs further attention.

PMID- 25765917
TI  - Psychometric Properties of a Decisional Capacity Screening Tool for Individuals
      Contemplating Participation in Alzheimer's Disease Research.
AB  - BACKGROUND: With the growing population of individuals affected by Alzheimer's
      disease (AD) and related disorders, there is a pressing demand for research on
      late-life cognitive disorders. However, this population's high risk for
      decisional incapacity necessitates evaluation of capacity to consent to research
      participation, adding cost and complexity to the research process. The University
      of California, San Diego Brief Assessment of Capacity to Consent (UBACC) was
      initially validated in a sample of persons with schizophrenia and healthy
      controls. OBJECTIVE: To assess the psychometric properties of the UBACC when used
      in a sample of individuals contemplating participation in AD research. METHODS:
      The UBACC was administered to a convenience sample (n = 132) consisting of
      individuals with mild to moderate cognitive impairment (n = 52), their study
      partners (n = 52), and healthy older adults control subjects (n = 30), as part of
      a broader study to evaluate perceived burden of research participation.
      Reliability tests, correlational analyses, and exploratory factor analytic
      methods were used to examine the psychometric properties of the instrument.
      RESULTS: UBACC scores were significantly associated with both global cognition
      (rs= 0.564, p <  0.001) and verbal fluency (rs = 0.511, p <  0.001), indicating
      concurrent validity with related constructs. The resulting factor structure
      differed from that reported by the developers in their initial testing. Items
      clustered almost entirely on one factor; items reflecting the construct of
      understanding accounted for 32.12% of total variance, with no evidence for
      distinct reasoning or appreciation scales. CONCLUSION: The UBACC shows promise
      when used to screen for decisional capacity among those considering participation
      in AD research.

PMID- 25765918
TI  - Differential Effects of Palmitoylethanolamide against Amyloid-beta Induced
      Toxicity in Cortical Neuronal and Astrocytic Primary Cultures from Wild-Type and
      3xTg-AD Mice.
AB  - BACKGROUND: Considering the heterogeneity of pathological changes occurring in
      Alzheimer's disease (AD), a therapeutic approach aimed both to neuroprotection
      and to neuroinflammation reduction may prove effective. Palmitoylethanolamide
      (PEA) has attracted attention for its anti-inflammatory/neuroprotective
      properties observed in AD animal models. OBJECTIVE AND METHODS: We evaluated the
      protective role of PEA against amyloid-beta42 (Abeta42) toxicity on cell
      viability and glutamatergic transmission in primary cultures of cerebral cortex
      neurons and astrocytes from the triple-transgenic murine model of AD (3xTg-AD)
      and their wild-type littermates (non-Tg) mice. RESULTS: Abeta42 (0.5 MUM; 24 h)
      affects the cell viability in cultured cortical neurons and astrocytes from non
      Tg mice, but not in those from 3xTg-AD mice. These effects were counteracted by
      the pretreatment with PEA (0.1 MUM). Basal glutamate levels in cultured neurons
      and astrocytes from 3xTg-AD mice were lower than those observed in cultured cells
      from non-Tg mice. Abeta42-exposure reduced and increased glutamate levels in non
      Tg mouse cortical neurons and astrocytes, respectively. These effects were
      counteracted by the pretreatment with PEA. By itself, PEA did not affect cell
      viability and glutamate levels in cultured cortical neurons and astrocytes from
      non-Tg or 3xTg-AD mice. CONCLUSION: The exposure to Abeta42 induced toxic effects
      on cultured cortical neurons and astrocytes from non-Tg mice, but not in those
      from 3xTg-AD mice. Furthermore, PEA exerts differential effects against Abeta42
      induced toxicity in primary cultures of cortical neurons and astrocytes from non
      Tg and 3xTg-AD mice. In particular, PEA displays protective properties in non-Tg
      but not in 3xTg-AD mouse neuronal cultured cells overexpressing Abeta.

PMID- 25765919
TI  - ITS so much more.

PMID- 25765921
TI  - Antioxidant and antiatherogenic properties of phenolic acid and flavonol
      fractions of fruits of 'Amari' and 'Hallawi' date (Phoenix dactylifera L.)
      varieties.
AB  - Date (Phoenix dactylifera L.) fruit phenolic-acid or flavonol fractions were
      examined in vitro for antioxidant and antiatherogenic properties. Two fractions
      of each subgroup were prepared from two date varieties, 'Amari' and 'Hallawi', by
      solid phase extraction on C18. The fractions were analyzed for phenolics
      composition by RP-HPLC and tested for ferric-reducing antioxidant power, free
      radical scavenging capacity, inhibition of Cu(2+)-induced LDL oxidation, and
      enhancement of HDL-mediated cholesterol efflux from macrophages. All four
      fractions exhibited variable capacities to reduce ferric ions, scavenge radicals,
      and inhibit LDL oxidation. Flavonol fractions were considerably better inhibitors
      of LDL oxidation compared to phenolic acid fractions, with IC50's of 9-31 nmol
      GAE mL(-1) compared to 85-116 nmol GAE mL(-1), respectively. Only the flavonol
      fractions stimulated cholesterol removal from macrophages. Within each subgroup,
      the levels of all the activities varied with fraction composition. The results
      demonstrated strong structure-activity relationships for date phenolics and
      identified date flavonols as potential antiatherogenic bioactives.

PMID- 25765922
TI  - Outcomes for Prenatally Diagnosed Right Congenital Diaphragmatic Hernia.
AB  - BACKGROUND: Right congenital diaphragmatic hernia (CDH) occurs less frequently
      than left CDH. Therefore, prognostic indicators for right CDH are not as well
      studied as for left CDH. METHODS: A retrospective review from a single, tertiary
      referral center (from 1994 until July 2013) of patients with unilateral right CDH
      was conducted. Prenatal characteristics were evaluated and correlated with
      survival to discharge and need for extracorporeal membranous oxygen (ECMO).
      RESULTS: In total, 34 patients were identified. There were 12 postnatal deaths
      and 2 fetal demises (6%), representing an overall mortality of 41%. Six patients
      required ECMO. Nine patients underwent fetal intervention and were analyzed
      separately. For patients not undergoing fetal intervention, the survival rate was
      52% and a higher mean (+/-SD) lung-to-head ratio (LHR) was associated with
      survival (1.1 +/- 0.4 vs. 0.8 +/- 0.2, p = 0.03). There were no deaths or need
      for ECMO in any patient with an LHR >=1.0. Of the 9 patients who underwent fetal
      intervention, survival was 78% and only 1 patient required ECMO. Fetal
      intervention was primarily tracheal occlusion (n = 8). CONCLUSIONS: An LHR <1.0
      is associated with worse survival for right CDH and may also reflect the need for
      ECMO. (c) 2015 S. Karger AG, Basel.

PMID- 25765920
TI  - Evolution and population genomics of the Lyme borreliosis pathogen, Borrelia
      burgdorferi.
AB  - Population genomic studies have the potential to address many unresolved
      questions about microbial pathogens by facilitating the identification of genes
      underlying ecologically important traits, such as novel virulence factors and
      adaptations to humans or other host species. Additionally, this framework
      improves estimations of population demography and evolutionary history to
      accurately reconstruct recent epidemics and identify the molecular and
      environmental factors that resulted in the outbreak. The Lyme disease bacterium,
      Borrelia burgdorferi, exemplifies the power and promise of the application of
      population genomics to microbial pathogens. We discuss here the future of
      evolutionary studies in B. burgdorferi, focusing on the primary evolutionary
      forces of horizontal gene transfer, natural selection, and migration, as
      investigations transition from analyses of single genes to genomes. 

PMID- 25765924
TI  - Is fibromyalgia a real pathology?

PMID- 25765923
TI  - Rapid genome resequencing of an atoxigenic strain of Aspergillus carbonarius.
AB  - In microorganisms, Ion Torrent sequencing technology has been proved to be useful
      in whole-genome sequencing of bacterial genomes (5 Mbp). In our study, for the
      first time we used this technology to perform a resequencing approach in a whole
      fungal genome (36 Mbp), a non-ochratoxin A producing strain of Aspergillus
      carbonarius. Ochratoxin A (OTA) is a potent nephrotoxin which is found mainly in
      cereals and their products, but it also occurs in a variety of common foods and
      beverages. Due to the fact that this strain does not produce OTA, we focused some
      of the bioinformatics analyses in genes involved in OTA biosynthesis, using a
      reference genome of an OTA producing strain of the same species. This study
      revealed that in the atoxigenic strain there is a high accumulation of nonsense
      and missense mutations in several genes. Importantly, a two fold increase in gene
      mutation ratio was observed in PKS and NRPS encoding genes which are suggested to
      be involved in OTA biosynthesis.

PMID- 25765925
TI  - The evolving genomic landscape of recurrent gliomas.

PMID- 25765926
TI  - Scalp Metastases of Recurrent Meningiomas: Aggressive Behavior or Surgical
      Seeding?
AB  - OBJECTIVE: Scalp metastases of meningiomas seldom have been reported. Here, we
      report a series of 4 cases of this rare event and discuss the relevant potential
      risk factors. METHODS: We performed a retrospective review of patients treated
      for scalp metastases of meningiomas at our institution. A literature review was
      performed for the terms "scalp meningioma," "cutaneous meningioma," "skin
      meningioma," "extracranial meningioma," and "subcutaneous meningioma." RESULTS:
      Four patients showed scalp metastases of recurrent meningiomas with the following
      associated clinical features: multiple reoperations (n = 4), immunosuppression (n
      = 2), radiation therapy (n = 3), surgical wound complications with cerebrospinal
      fluid fistula (n = 2), and histologic grade progression (n = 2). The timescale
      for development of scalp metastasis was between 5 months and 13 years after
      intracranial meningioma surgery. In all cases, the metastases were located close
      to the surgical scalp incision for the craniotomy. Previously, 11 cases of
      meningioma with scalp metastasis, with similar features to those described here,
      were reported in the literature. CONCLUSIONS: Spreading of meningioma cells
      during surgery is a possible mechanism for scalp metastases of recurrent
      meningiomas. Factors associated with scalp metastases include reoperations,
      immunosuppression, radiation therapy, torpid course of the surgical wound with
      cerebrospinal fluid fistula, and histologic progression. Awareness of these
      features is advisable for neurosurgeons involved in the care of patients with
      similar profiles.

PMID- 25765927
TI  - Effects of different classes of antihypertensive agents on the outcome of acute
      ischemic stroke.
AB  - It is unclear whether antihypertensive treatment before stroke affects acute
      ischemic stroke severity and outcome. To evaluate this association, the authors
      studied 482 consecutive patients (age 78.8+/-6.7 years) admitted with acute
      ischemic stroke. Stroke severity was assessed at admission with the National
      Institutes of Health Stroke Scale (NIHSS). The outcome was assessed with rates of
      adverse outcome (modified Rankin scale at discharge >=2). Independent predictors
      of severe stroke (NIHSS >=16) were female sex and atrial fibrillation. Treatment
      with diuretics before stroke was associated with nonsevere stroke. At discharge,
      patients with adverse outcome were less likely to be treated before stroke with
      beta-blockers or with diuretics. Independent predictors of adverse outcome were
      older age, higher NIHSS at admission, and history of ischemic stroke. Treatment
      with diuretics before stroke appears to be associated with less severe neurologic
      deficit in patients with acute ischemic stroke.

PMID- 25765929
TI  - The a.c. Josephson effect without superconductivity.
AB  - Superconductivity derives its most salient features from the coherence of the
      associated macroscopic wave function. The related physical phenomena have now
      moved from exotic subjects to fundamental building blocks for quantum circuits
      such as qubits or single photonic modes. Here we predict that the a.c. Josephson
      effect-which transforms a d.c. voltage Vb into an oscillating signal cos
      (2eVbt/h)-has a mesoscopic counterpart in normal conductors. We show that when a
      d.c. voltage Vb is applied to an electronic interferometer, there exists a
      universal transient regime where the current oscillates at frequency eVb/h. This
      effect is not limited by a superconducting gap and could, in principle, be used
      to produce tunable a.c. signals in the elusive 0.1-10-THz 'terahertz gap'. 

PMID- 25765928
TI  - Epigenetic and developmental regulation in plant polyploids.
AB  - Polyploidy or whole-genome duplication occurs in some animals and many flowering
      plants, including many important crops such as wheat, cotton and oilseed rape.
      The prevalence of polyploidy in the plant kingdom suggests it as an important
      evolutionary feature for plant speciation and crop domestication. Studies of
      natural and synthetic polyploids have revealed rapid and dynamic changes in
      genomic structure and gene expression after polyploid formation. Growing evidence
      suggests that epigenetic modifications can alter homoeologous gene expression and
      reprogram gene expression networks, which allows polyploids to establish new
      cytotypes, grow vigorously and promote adaptation in local environments. Sequence
      and gene expression changes in polyploids have been well documented and reviewed
      elsewhere. This review is focused on developmental regulation and epigenetic
      changes including DNA methylation and histone modifications in polyploids. 

PMID- 25765930
TI  - Hepatitis B reactivation in HBsAg-negative/HBcAb-positive patients receiving
      rituximab for lymphoma: a meta-analysis.
AB  - Patients with chronic hepatitis B (HBsAg-positive) are at risk of viral
      reactivation if rituximab is administered without antiviral treatment, a
      potentially fatal complication of treatment. Patients with so-called 'resolved
      hepatitis B virus infection' (HBsAg-negative/cAb-positive) may also be at risk.
      We performed a systematic review of the English and Chinese language literature
      to estimate the risk of hepatitis B virus (HBV) reactivation in HBsAg
      negative/cAb-positive patients receiving rituximab for lymphoma. A pooled risk
      estimate was calculated for HBV reactivation. The impact of HBsAb status and
      study design on reactivation rates was explored. Data from 578 patients in 15
      studies were included. 'Clinical HBV reactivation', (ALT >3 * normal and either
      an increase in HBV DNA from baseline or HBsAg seroreversion), was estimated at
      6.3% (I(2) = 63%, P = 0.006). Significant heterogeneity was detected.
      Reactivation rates were higher in prospective vs retrospective studies (14.2% vs
      3.8%; OR = 4.39, 95% CI 0.83-23.28). Exploratory analyses found no effect of
      HBsAb status on reactivation risk (OR = 0.083; P = 0.151). Our meta-analysis
      confirms a measurable and potentially substantial risk of HBV reactivation in
      HBsAg-negative/cAb-positive patients exposed to rituximab. However, heterogeneity
      in the existing literature limits the generalizability of our findings. Large,
      prospective studies, with uniform definitions of HBV reactivation, are needed to
      clarify the risk of HBV reactivation in HBsAg-negative/cAb-positive patients.

PMID- 25765932
TI  - Factors affecting the utilisation of maternal, newborn, and child health services
      in Indonesia: the role of the Maternal and Child Health Handbook.

PMID- 25765931
TI  - Atenolol offers better protection than clonidine against cardiac injury in kainic
      acid-induced status epilepticus.
AB  - BACKGROUND AND PURPOSE: Status epilepticus is increasingly associated with
      cardiac injury in both clinical and animal studies. The current study examined
      ECG activity for up to 48 h following kainic acid (KA) seizure induction and
      compared the potential of atenolol and clonidine to attenuate this cardiac
      pathology. EXPERIMENTAL APPROACH: Sprague-Dawley rats (male, 300-350 g) were
      implanted with ECG and electrocorticogram electrodes to allow simultaneous
      telemetric recordings of cardiac and cortical responses during and after KA
      induced seizures. Animals were randomized into saline controls, and saline
      vehicle-, clonidine- or atenolol-pretreated KA groups. KEY RESULTS: KA
      administration in the saline-pretreated group produced an immediate bradycardic
      response (maximal decrease of 28 +/- 6%), coinciding with low-level seizure
      activity. As high-level seizure behaviours and EEG spiking increased, tachycardia
      also developed, with a maximum heart rate increase of 38 +/- 7% coinciding with
      QTc prolongation and T wave elevation. Both clonidine and atenolol pretreatment
      attenuated seizure activity and reduced KA-induced changes in heart rate, QTc
      interval and T wave amplitude observed during both bradycardic and tachycardic
      phases in saline-pretreated KA animals. Clonidine, however, failed to reduce the
      power of EEG frequencies. Atenolol and to a lesser extent clonidine attenuated
      the cardiac hypercontraction band necrosis, inflammatory infiltration, and oedema
      at 48 h after KA, relative to the saline-KA group. CONCLUSIONS AND IMPLICATIONS:
      Severe seizure activity in this model was clearly associated with altered ECG
      activity and cardiac pathology. We suggest that modulation of sympathetic
      activity by atenolol provides a promising cardioprotective approach in status
      epilepticus.

PMID- 25765933
TI  - Antibiotic use in Chinese hospitals: a multicenter point-prevalence study.

PMID- 25765934
TI  - Life skills education of rural families in Iran: a community-based participatory
      study.

PMID- 25765935
TI  - Lung deposition of nebulized surfactant in newborn piglets.
AB  - BACKGROUND: It would be advantageous for the treatment of neonatal respiratory
      distress syndrome if effective amounts of surfactant could be delivered by
      nebulization. OBJECTIVE: To investigate lung deposition and distribution of
      nebulized porcine surfactant using an investigational eFlow neonatal nebulizer.
      METHODS: While lying on one side, 1-day-old piglets inhaled 200 mg.kg(-1) of
      nebulized surfactant via mask, nasal prongs, or tracheal tube. The surfactant was
      diluted with normal saline to 40 mg.ml(-1) and labeled with (99m)technetium
      labelled nanocolloid. Undiluted surfactant (80 mg.ml(-1)) was instilled
      tracheally in a fourth group. Each group had 8 animals. Lung deposition was
      measured by gamma scintigraphy, and deposition values were presented as a
      percentage of the nebulized or instilled dose. RESULTS: The median lung
      deposition of inhaled surfactant was 5% (range 3-16) via mask, 14% (2-40) via
      prongs, and 45% (25-56) via tracheal tube (p < 0.05). It was 88% (71-96) with
      instillation. In all groups, the surfactant preferentially went to the dependent
      lung. Deposition ratios (upper lung/both lungs) were 0.32 (0.13-0.58), 0.15 (0.05
      0.58), 0.16 (0.11-0.23), and 0.08 (0.03-0.46). CONCLUSIONS: Using this nebulizer,
      the lung depositions of porcine surfactant were 45% via endotracheal tube and 14%
      via nasal-continuous positive airway pressure (prongs). These figures might be
      physiologically relevant, but still have to be confirmed in efficacy studies.

PMID- 25765936
TI  - Good and bad consequences of altered fatty acid metabolism in heart failure:
      evidence from mouse models.
AB  - The shift in substrate preference away from fatty acid oxidation (FAO) towards
      increased glucose utilization in heart failure has long been interpreted as an
      oxygen-sparing mechanism. Inhibition of FAO has therefore evolved as an accepted
      approach to treat heart failure. However, recent data indicate that increased
      reliance on glucose might be detrimental rather than beneficial for the failing
      heart. This review discusses new insights into metabolic adaptations in heart
      failure. A particular focus lies on data obtained from mouse models with
      modulations of cardiac FA metabolism at different levels of the FA metabolic
      pathway and how these differently affect cardiac function. Based on studies in
      which these mouse models were exposed to ischaemic and non-ischaemic heart
      failure, we discuss whether and when modulations in FA metabolism are protective
      against heart failure. 

PMID- 25765937
TI  - Oestrogen receptor alpha in pulmonary hypertension.
AB  - AIMS: Pulmonary arterial hypertension (PAH) occurs more frequently in women with
      mutations in bone morphogenetic protein receptor type 2 (BMPR2) and dysfunctional
      BMPR2 signalling underpinning heritable PAH. We have previously shown that
      serotonin can uncover a pulmonary hypertensive phenotype in BMPR2(+/-) mice and
      that oestrogen can increase serotinergic signalling in human pulmonary arterial
      smooth muscle cells (hPASMCs). Hence, here we wished to characterize the
      expression of oestrogen receptors (ERs) in male and female human pulmonary
      arteries and have examined the influence of oestrogen and serotonin on BMPR2 and
      ERalpha expression. METHODS AND RESULTS: By immunohistochemistry, we showed that
      ERalpha, ERbeta, and G-protein-coupled receptors are expressed in human pulmonary
      arteries localizing mainly to the smooth muscle layer which also expresses the
      serotonin transporter (SERT). Protein expression of ERalpha protein was higher in
      female PAH patient hPASMCs compared with male and serotonin also increased the
      expression of ERalpha. 17beta-estradiol induced proliferation of hPASMCs via
      ERalpha activation and this engaged mitogen-activated protein kinase and Akt
      signalling. Female mice over-expressing SERT (SERT(+) mice) develop PH and the
      ERalpha antagonist MPP attenuated the development of PH in normoxic and hypoxic
      female SERT(+) mice. The therapeutic effects of MPP were accompanied by increased
      expression of BMPR2 in mouse lung. CONCLUSION: ERalpha is highly expressed in
      female hPASMCs from PAH patients and mediates oestrogen-induced proliferation of
      hPASMCs via mitogen-activated protein kinase and Akt signalling. Serotonin can
      increase ERalpha expression in hPASMCs and antagonism of ERalpha reverses
      serotonin-dependent PH in the mouse and increases BMPR2 expression.

PMID- 25765939
TI  - Cp2TiCl2-catalyzed cis-hydroalumination of propargylic amines with Red-Al:
      stereoselective synthesis of Z-configured allylic amines.
AB  - A titanium-catalyzed cis-hydroalumination of propargylic amines with Red-Al is
      described, which provides an efficient way to produce Z-configured allylic amines
      in good to excellent yields with high stereoselectivity and good
      regioselectivity. The hydride-bridged Al/Ti bimetallic species may act as a real
      catalyst in this reaction. 

PMID- 25765938
TI  - Chemokine receptors CXCR2 and CX3CR1 differentially regulate functional responses
      of bone-marrow endothelial progenitors during atherosclerotic plaque regression.
AB  - AIMS: Atherosclerosis manifests itself as arterial plaques, which lead to heart
      attacks or stroke. Treatments supporting plaque regression are therefore
      aggressively pursued. Studies conducted in models in which hypercholesterolaemia
      is reversible, such as the Reversa mouse model we have employed in the current
      studies, will be instrumental for the development of such interventions. Using
      this model, we have shown that advanced atherosclerosis regression occurs when
      lipid lowering is used in combination with bone-marrow endothelial progenitor
      cell (EPC) treatment. However, it remains unclear how EPCs home to regressing
      plaques and how they augment atherosclerosis reversal. Here we identify molecules
      that support functional responses of EPCs during plaque resolution. METHODS AND
      RESULTS: Chemokines CXCL1 and CX3CL1 were detected in the vascular wall of
      atheroregressing Reversa mice, and their cognate receptors CXCR2 and CX3CR1 were
      observed on adoptively transferred EPCs in circulation. We tested whether CXCL1
      CXCR2 and CX3CL1-CX3CR1 axes regulate functional responses of EPCs during plaque
      reversal. We show that pharmacological inhibition of CXCR2 or CX3CR1, or genetic
      inactivation of these two chemokine receptors interfered with EPC-mediated
      advanced atherosclerosis regression. We also demonstrate that CXCR2 directs EPCs
      to regressing plaques while CX3CR1 controls a paracrine function(s) of these
      cells. CONCLUSION: CXCR2 and CX3CR1 differentially regulate EPC functional
      responses during atheroregression. Our study improves understanding of how
      chemokines and chemokine receptors regulate plaque resolution, which could
      determine the effectiveness of interventions reducing complications of
      atherosclerosis.

PMID- 25765941
TI  - The Effect of Peripapillary Detachment on Retinal Nerve Fiber Layer Measurement
      by Spectral Domain Optical Coherence Tomography in High Myopia.
AB  - PURPOSE: The aim of this study was to investigate the repercussions of
      peripapillary detachment on retinal nerve fiber layer (RNFL) measurements in
      patients with highly myopic eyes. METHODS: A total of 244 highly myopic eyes
      underwent a complete ophthalmologic examination that included optical coherence
      tomography (OCT) to analyze the peripapillary retina and RNFL thickness. Based on
      the OCT findings, patients were grouped as follows: group A: eyes with a
      peripapillary intrachoroidal cavitation (PIC); group B: eyes with a peripapillary
      neurosensory retinal detachment (PNRD), and group C: eyes without a peripapillary
      detachment. RESULTS: The OCT scans identified a peripapillary detachment in 42
      eyes (17.21%). Out of these 42 eyes, 22 showed PIC (52.38%; group A) and 20 had a
      PNRD (47.62%; group B). The average overall RNFL thickness in groups A, B and C
      was 74.11 +/- 10.88, 88.26 +/- 25.72 and 72.75 +/- 16.24 MUm, respectively (ANOVA
      test, p = 0.00). CONCLUSION: Eyes with a PNRD had a significantly greater average
      RFNL thickness than those without peripapillary detachment in pathologic myopia
      due to a misidentification of the outer profile of the RFNL. This fact makes the
      interpretation of RNFL thickness in highly myopic eyes more challenging.

PMID- 25765942
TI  - Allergen skin prick test should be adjusted by the histamine reactivity.
AB  - BACKGROUND: Skin prick test results are mostly reported as mean wheal diameter
      obtained with one concentration of allergen. Differences in technique between
      personnel causes variation in wheal size. The research question was whether the
      influence of differences in skin prick test technique among assistants and
      centers can be reduced by relating the allergen wheal response to that of
      histamine. METHODS: Two methods for estimating skin reactivity, the method of
      Nordic Guidelines using histamine as a reference and the method of Brighton et
      al. [Clin Allergy 1979;9:591-596] not using histamine as a reference, were
      applied to data from two biological standardization trials, using the same batch
      of freeze-dried timothy pollen preparation. RESULTS: The concentration defining
      the Nordic biological unit, defined as a concentration of allergen eliciting a
      wheal of the same size as that of histamine dihydrochloride 10 mg/ml, did not
      differ between the centers. When not using histamine as a reference, applying the
      method of Brighton et al., there was a 15-fold difference in the estimate of the
      biological activity between the trials that was eliminated by adjusting the
      allergen response to that of the histamine reference. CONCLUSIONS: To reduce the
      influence of differences in test technique among assistants and centers responses
      to allergen-induced skin prick tests should be compared to that of histamine.

PMID- 25765944
TI  - Does beta-Catenin Cross-Regulate NFkappaB Signalling in Pancreatic Cancer and
      Chronic Pancreatitis?
AB  - BACKGROUND: It is not clear by which mechanism nuclear factor-kappaB (NFkappaB)
      induces cell proliferation and escapes from the apoptotic pathway in pancreatic
      carcinogenesis. This study aimed to investigate beta-catenin and NFkappaB
      signalling in chronic pancreatitis and pancreatic cancer. MATERIALS AND METHODS:
      On tissue samples of chronic pancreatitis and pancreatic cancer, we performed
      immunohistochemistry for detecting the expression of tumour necrosis factor alpha
      (TNFalpha), beta-catenin and NFkappaB, Western blot for TNFalpha, NFkappaB, beta
      catenin, c-Myc and FasL, co-immunoprecipitation for beta-catenin with NFkappaB
      and RT-PCR for cyclin D1, c-Myc and Fas. RESULTS: TNFalpha and NFkappaB
      expression was increased in chronic pancreatitis and pancreatic cancer. beta
      Catenin and cyclin D1 expression was intense in pancreatic cancer and moderate in
      chronic pancreatitis. Of the NFkappaB response elements, the expression of pro
      proliferative c-Myc is intense in pancreatic cancer and moderate in chronic
      pancreatitis, but the pro-apoptotic factors, Fas and FasL were down-regulated in
      pancreatic cancer and moderately expressed in chronic pancreatitis. The co
      immunoprecipitation results showed a significant interaction of beta-catenin with
      NFkappaB in pancreatic cancer and a non-significant interaction in chronic
      pancreatitis. CONCLUSIONS: beta-Catenin might cross-regulate NFkappaB by
      interrupting the balance of cell death and cell survival via recruiting NFkappaB
      into the cell survival pathway alone in most cases of pancreatic cancer and some
      cases of chronic pancreatitis. (c) 2015 S. Karger AG, Basel.

PMID- 25765943
TI  - Monitoring disease trends using hospital traffic data from high resolution
      satellite imagery: a feasibility study.
AB  - Challenges with alternative data sources for disease surveillance include
      differentiating the signal from the noise, and obtaining information from data
      constrained settings. For the latter, events such as increases in hospital
      traffic could serve as early indicators of social disruption resulting from
      disease. In this study, we evaluate the feasibility of using hospital parking lot
      traffic data extracted from high-resolution satellite imagery to augment public
      health disease surveillance in Chile, Argentina and Mexico. We used archived
      satellite imagery collected from January 2010 to May 2013 and data on the
      incidence of respiratory virus illnesses from the Pan American Health
      Organization as a reference. We developed dynamical Elastic Net multivariable
      linear regression models to estimate the incidence of respiratory virus illnesses
      using hospital traffic and assessed how to minimize the effects of noise on the
      models. We noted that predictions based on models fitted using a sample of
      observations were better. The results were consistent across countries with
      selected models having reasonably low normalized root-mean-squared errors and
      high correlations for both the fits and predictions. The observations from this
      study suggest that if properly procured and combined with other information, this
      data source could be useful for monitoring disease trends. 

PMID- 25765945
TI  - Covalent attachment of Anderson-type polyoxometalates to single-walled carbon
      nanotubes gives enhanced performance electrodes for lithium ion batteries.
AB  - Single-walled carbon nanotubes (SWNTs) covalently functionalized with redox
      active organo-modified polyoxometalate (POM) clusters have been synthesized and
      employed as electrode materials in lithium ion batteries. The Anderson cluster
      [MnMo6 O24 ](9-) is functionalized with Tris (NH2 C(CH2 OH)3 ) moieties, giving
      the new organic-inorganic hybrid [N(nC4 H9 )4 ]3 [MnMo6 O18 {(OCH2 )3 CNH2 }2 ].
      The compound is then covalently attached to carboxylic acid-functionalized SWNTs
      by amide bond formation and the stability of this nanocomposite is confirmed by
      various spectroscopic methods. Electrochemical analyses show that the
      nanocomposite displays improved performance as an anode material in lithium ion
      batteries compared with the individual components, that is, SWNTs and/or Anderson
      clusters. High discharge capacities of up to 932 mAh g(-1) at a current density
      of 0.5 mA cm(-2) can be observed, together with high long-term cycling stability
      and decreased electrochemical impedance. Chemisorption of the POM cluster on the
      SWNTs is shown to give better electrode performance than the purely physisorbed
      analogues.

PMID- 25765946
TI  - Dynamic balance assessment during gait in spinal pathologies - a literature
      review.
AB  - The role of the spine as a gait stabilizer is essential. Dynamic assessment,
      while walking, might provide complementary data to improve spinal deformity
      management. The aim of this paper was to review spine dynamic behavior and the
      various methods that have been used to assess gait dynamic balance in order to
      explore the consequences of spinal deformities while walking. A review was
      performed by obtaining publications from five electronic databases. All papers
      reporting pathological or non-pathological spine dynamic behavior during gait and
      dynamic balance assessment methods were included. Sixty articles were selected.
      Results varied widely according to pathologies, study conditions, and balance
      assessment techniques. Three methods assessing dynamic stability during gait were
      identified: local-orbital dynamic stability, tri-axial accelerometry, and dynamic
      stability margin. Data from conventional gait analysis techniques were
      established essentially for scoliosis and low back pain, but they do not assess
      specific consequences on gait dynamic balance. Three techniques investigate gait
      dynamic balance and have been validated in normal subjects. Further
      investigations need to be performed for validation in spinal pathologies as well
      as the value for clinical practice. LEVEL OF EVIDENCE: Level IV.

PMID- 25765947
TI  - Comments on: "Femoral head diameter considerations for primary total hip
      arthroplasty" by J. Girard published in Orthop Trauma Surg Res 2015;101:S25-9.

PMID- 25765948
TI  - Forming-free and self-rectifying resistive switching of the simple Pt/TaOx/n-Si
      structure for access device-free high-density memory application.
AB  - The search for self-rectifying resistive memories has aroused great attention due
      to their potential in high-density memory applications without additional access
      devices. Here we report the forming-free and self-rectifying bipolar resistive
      switching behavior of a simple Pt/TaOx/n-Si tri-layer structure. The forming-free
      phenomenon is attributed to the generation of a large amount of oxygen vacancies,
      in a TaOx region that is in close proximity to the TaOx/n-Si interface, via out
      diffusion of oxygen ions from TaOx to n-Si. A maximum rectification ratio of ~6 *
      10(2) is obtained when the Pt/TaOx/n-Si devices stay in a low resistance state,
      which originates from the existence of a Schottky barrier between the formed
      oxygen vacancy filament and the n-Si electrode. More importantly, numerical
      simulation reveals that the self-rectifying behavior itself can guarantee a
      maximum crossbar size of 212 * 212 (~44 kbit) on the premise of 10% read margin.
      Moreover, satisfactory switching uniformity and retention performance are
      observed based on this simple tri-layer structure. All of these results
      demonstrate the great potential of this simple Pt/TaOx/n-Si tri-layer structure
      for access device-free high-density memory applications. 

PMID- 25765949
TI  - Embolectomy for stroke with emergent large vessel occlusion (ELVO): report of the
      Standards and Guidelines Committee of the Society of NeuroInterventional Surgery.

PMID- 25765950
TI  - Evaluation of time to aneurysm treatment following subarachnoid hemorrhage:
      comparison of patients treated with clipping versus coiling.
AB  - INTRODUCTION: Prior studies of aneurysmal subarachnoid hemorrhage (SAH) have
      shown that treatment at teaching institutions and decreased time to surgery are
      factors that correlate with improved patient outcome. We aimed to individually
      evaluate the effect of teaching institution treatment on rates of surgical
      clipping or endovascular coiling. METHODS: Patients with SAH treated by either
      aneurysm clipping or coiling between 2002 and 2010 in the Nationwide Inpatient
      Sample were analyzed. Time to aneurysm treatment was dichotomized to >3 days or
      <=3 days and evaluated by multivariable logistic regression modeling, controlling
      for patient and hospital covariates. Identified predictors for prolonged time to
      procedure were compared between the clipping and coiling populations. RESULTS:
      Between 2002 and 2010 there were 90 684 SAH admissions with subsequent clipping
      and coiling procedures. Treatment at teaching hospitals was associated with
      faster time to clipping (OR 0.60, 95% CI 0.44 to 0.80, p=0.001) but not coiling
      procedures (p=0.66). Likewise, older age (>=80 years) was associated with delays
      to clipping (p<0.05) but not coiling procedures (p>0.05). Patients with delayed
      time to treatment were associated with increased rates of moderate to severe
      neurological disability. CONCLUSIONS: Older patients with SAH and those treated
      at non-teaching hospitals were more likely to have delays to aneurysm clipping
      procedures. These associations were unique to open surgery as age and hospital
      teaching status did not affect time to coiling procedures.

PMID- 25765951
TI  - Asymmetric synthesis of (S)-4-chloro-3-hydroxybutanoate by sorbose reductase from
      Candida albicans with two co-existing recombinant Escherichia coli strains.
AB  - An NADPH-dependent sorbose reductase from Candida albicans was identified to
      catalyze the asymmetric reduction of ethyl 4-chloro-3-oxobutanoate (COBE). The
      activity of the recombinant enzyme toward COBE was 6.2 U/mg. The asymmetric
      reduction of COBE was performed with two coexisting recombinant Escherichia coli
      strains, in which the recombinant E. coli expressing glucose dehydrogenase was
      used as an NADPH regenerator. An optical purity of 99% (e.e.) and a maximum yield
      of 1240 mM (S)-4-chloro-3-hydroxybutanoate were obtained under an optimal biomass
      ratio of 1:2. A highest turnover number of 53,900 was achieved without adding
      extra NADP(+)/NADPH compared with those known COBE-catalytic systems.

PMID- 25765952
TI  - A randomized trial comparing adjuvant chemotherapy with gemcitabine plus
      cisplatin with docetaxel plus cisplatin in patients with completely resected non
      small-cell lung cancer with quality of life as the primary objective.
AB  - OBJECTIVES: Adjuvant chemotherapy with vinorelbine plus cisplatin (VC) improves
      survival in resected non-small-cell lung cancer (NSCLC), but has negative impact
      on quality of life (QoL). In advanced NSCLC, gemcitabine plus cisplatin (GC) and
      docetaxel plus cisplatin (DC) exhibit comparable efficacy, with possibly superior
      QoL compared to VC. This trial investigated these regimens in the adjuvant
      setting. METHODS: Patients with Stage IB to III NSCLC were eligible following
      standardized surgery. Overall, 136 patients were included, with 67 and 69
      assigned to the GC and DC arms, respectively. Cisplatin (75 mg/m(2), Day [D] 1)
      plus gemcitabine (1250 mg/m(2), D1 and D8) or docetaxel (75 mg/m(2) D1) were
      administered for three cycles. Primary end-point was QoL (EORTC QLQ-C30), with
      the study designed to detect a 10-point difference between arms. Overall
      survival, safety and cost were secondary end-points. RESULTS: No between-group
      imbalance was observed in terms of patient characteristics. At inclusion, global
      health status (GHS) scores (/100) were 63.5 and 62.7 in GC and DC, respectively
      (P = 0.8), improving to 64.5 and 65.4 after 3 months (P = 0.8). No significant
      difference in functional or symptoms scores was observed between the arms except
      for alopecia. Grade 3/4 haematological and non-haematological toxicities were
      found in 33.8 and 21.7% (P = 0.11), and 33.8 and 26.1% (P = 0.33) of patients, in
      GC and DC, respectively. At 2 years, 92.9 and 89.8% of patients remained alive in
      GC and DC, respectively (P = 0.88). CONCLUSIONS: DC and GC adjuvant
      chemotherapies for completely resected NSCLC were well tolerated and appear free
      of major QoL effects, and are therefore representing candidates for comparison
      with the standard VC regimen.

PMID- 25765953
TI  - Estrogen enhances secretion of apolipoprotein B-100 containing lipoproteins by
      BeWo cells.
AB  - Although the early human embryo is capable of covering its cholesterol demand by
      endogenous synthesis, during later stages of development the fetus may become
      dependent on transplacental cholesterol transport. On one hand, this conclusion
      is based on the severe developmental abnormalities of embryos with mutations in
      the gene specifying the enzyme catalyzing the last step of cholesterol synthesis,
      7-dehydrocholesterol reductase, causing Smith-Lemli-Opitz Syndrome. On the other
      hand, increased total maternal plasma cholesterol levels may reflect the
      requirement by the growing fetus and/or the placenta for cholesterol. Various
      molecules and complexes must cross the placental barrier consisting of
      trophoblasts and fetal endothelial cells to reach the fetal circulation. The de
      novo synthesis of apolipoprotein B (apoB)-containing lipoproteins coupled to
      secretion from trophoblasts towards the fetal side is one efficient pathway for
      cholesterol supply. ApoB and the microsomal triglyceride transfer protein (MTP)
      are essential components for the assembly of apoB-containing lipoproteins. The
      aim of this study was to evaluate functional properties of the human placental
      cell line BeWo as an in vitro model for placental synthesis of apoB-containing
      lipoproteins by focusing on components required for lipoprotein assembly and
      secretion. We demonstrate mRNA and protein production of apoB-100, MTP, and
      protein disulfide isomerase (PDI) in BeWo cells. In addition, metabolic
      radiolabeling and apoB-immunoprecipitation of cell extracts and media revealed
      that synthesis and secretion of apoB-containing lipoproteins are enhanced by
      estrogen. The expression of apoB-100, MTP, and PDI, and the estrogen-stimulated
      lipoprotein secretion by BeWo cells suggest that these cells are a useful system
      to study aspects of lipoprotein metabolism at the placental barrier. 

PMID- 25765954
TI  - Reference ranges for and determinants of right ventricular area in healthy adults
      by two-dimensional echocardiography.
AB  - BACKGROUND: The right ventricular (RV) area is important for diagnosis and follow
      up in patients with various diseases, such as in pulmonary hypertension.
      OBJECTIVES: The aim of this study was to define the reference ranges of the end
      diastolic RV area in healthy adults and to assess the determining factors.
      METHODS: In the first part of the study 860 healthy subjects (37.6% female; mean
      age 28 +/- 5.84; 395 endurance athletes, 255 strength athletes and 210 non
      athletes) were prospectively assessed. In the second part we performed a pooled
      analysis of studies published between 1979 and 2014 describing the RV area in
      healthy subjects (n = 5,248). Statistical analysis included the calculation of
      reference ranges and the analysis of determining factors. RESULTS: Mean end
      diastolic RV areas in 860 healthy subjects were significantly larger in endurance
      athletes (25.1 +/- 2.0 cm(2)) compared with strength athletes (22.9 +/- 1.7
      cm(2)) and non-athletes (16.7 +/- 2.0 cm(2), p < 0.001). In the synopsis of both
      data sets, mean end-diastolic RV area was significantly larger in
      European/American males (17 cm(2)) compared with females (14 cm(2), p < 0.001)
      and in Asian males (16 cm(2)) compared with females (13 cm(2), p < 0.001). The
      area increased with body surface area and older age. CONCLUSION: This is the
      largest data set to define RV size in healthy adults aged <50 years. RV area was
      determined by age, gender, body surface area, ethnicity and high-level exercise
      training. High standard deviations resulted in high values for the upper limit of
      the reference range, which might therefore not be useful as cut-off values for
      screening purposes. Gender- and ethnicity-specific reference ranges should be
      used. Further studies in subjects aged >50 years as well as in children are
      needed.

PMID- 25765955
TI  - Robust fuzzy output feedback controller for affine nonlinear systems via T-S
      fuzzy bilinear model: CSTR benchmark.
AB  - In this paper, a robust Hinfinity fuzzy output feedback controller is designed
      for a class of affine nonlinear systems with disturbance via Takagi-Sugeno (T-S)
      fuzzy bilinear model. The parallel distributed compensation (PDC) technique is
      utilized to design a fuzzy controller. The stability conditions of the overall
      closed loop T-S fuzzy bilinear model are formulated in terms of Lyapunov function
      via linear matrix inequality (LMI). The control law is robustified by Hinfinity
      sense to attenuate external disturbance. Moreover, the desired controller gains
      can be obtained by solving a set of LMI. A continuous stirred tank reactor
      (CSTR), which is a benchmark problem in nonlinear process control, is discussed
      in detail to verify the effectiveness of the proposed approach with a comparative
      study.

PMID- 25765956
TI  - State-dependent differential Riccati equation to track control of time-varying
      systems with state and control nonlinearities.
AB  - This work studies an optimal control problem using the state-dependent Riccati
      equation (SDRE) in differential form to track for time-varying systems with state
      and control nonlinearities. The trajectory tracking structure provides two
      nonlinear differential equations: the state-dependent differential Riccati
      equation (SDDRE) and the feed-forward differential equation. The independence of
      the governing equations and stability of the controller are proven along the
      trajectory using the Lyapunov approach. Backward integration (BI) is capable of
      solving the equations as a numerical solution; however, the forward solution
      methods require the closed-form solution to fulfill the task. A closed-form
      solution is introduced for SDDRE, but the feed-forward differential equation has
      not yet been obtained. Different ways of solving the problem are expressed and
      analyzed. These include BI, closed-form solution with corrective assumption,
      approximate solution, and forward integration. Application of the tracking
      problem is investigated to control robotic manipulators possessing rigid or
      flexible joints. The intention is to release a general program for automatic
      implementation of an SDDRE controller for any manipulator that obeys the Denavit
      Hartenberg (D-H) principle when only D-H parameters are received as input data. 

PMID- 25765957
TI  - Dimensionality reduction of RKHS model parameters.
AB  - This paper proposes a new method to reduce the parameter number of models
      developed in the Reproducing Kernel Hilbert Space (RKHS). In fact, this number is
      equal to the number of observations used in the learning phase which is assumed
      to be high. The proposed method entitled Reduced Kernel Partial Least Square
      (RKPLS) consists on approximating the retained latent components determined using
      the Kernel Partial Least Square (KPLS) method by their closest observation
      vectors. The paper proposes the design and the comparative study of the proposed
      RKPLS method and the Support Vector Machines on Regression (SVR) technique. The
      proposed method is applied to identify a nonlinear Process Trainer PT326 which is
      a physical process available in our laboratory. Moreover as a thermal process
      with large time response may help record easily effective observations which
      contribute to model identification. Compared to the SVR technique, the results
      from the proposed RKPLS method are satisfactory. 

PMID- 25765958
TI  - Finite time stability of nonlinear impulsive systems and its applications in
      sampled-data systems.
AB  - In this paper, we establish finite time stability (FTS) criteria for the
      nonlinear impulsive systems. By using a new concept called average impulse
      interval (AII), less conservative conditions are obtained for the FTS problem on
      the impulsive systems. Then we consider the linear time-invariant sampled-data
      systems by modeling such systems as linear impulsive systems. It is proved that
      when the AII of a sequence of impulsive signals zeta is equal to taualpha, the
      upper bound of the impulsive intervals could be very large, while the lower bound
      of the impulsive intervals could be also small enough. The obtained results are
      less conservative than the ones in the literature obtained for variable sampling
      intervals. 

PMID- 25765959
TI  - Glutenase and collagenase activities of wheat cysteine protease Triticain-alpha:
      feasibility for enzymatic therapy assays.
AB  - Insufficient and/or improper protein degradation is associated with the
      development of various human pathologies. Enzymatic therapy with proteolytic
      enzymes aimed to improve insufficient proteolytic activity was suggested as a
      treatment of protease deficiency-induced disorders. Since in many cases human
      degradome is incapable of degrading the entire target protein(s), other organisms
      can be used as a source of proteases exhibiting activities distinct from human
      enzymes, and plants are perspective candidates for this source. In this study
      recombinant wheat cysteine protease Triticain-alpha was shown to refold in vitro
      into an autocatalytically activated proteolytic enzyme possessing glutenase and
      collagenase activities at acidic (or close to neutral) pH levels at the
      temperature of human body. Mass-spectrometry analysis of the products of
      Triticain-alpha-catalyzed gluten hydrolysis revealed multiple cleavage sites
      within the sequences of gliadin toxic peptides, in particular, in the major toxic
      33-mer alpha-gliadin-derived peptide initiating inflammatory responses to gluten
      in celiac disease (CD) patients. Triticain-alpha was found to be relatively
      stable in the conditions simulating stomach environment. We conclude that
      Triticain-alpha can be exploited as a basic compound for development of (i)
      pharmaceuticals for oral administration aimed at release of the active enzyme
      into the gastric lumen for CD treatment, and (ii) topically active
      pharmaceuticals for wound debridement applications. 

PMID- 25765961
TI  - Aspects of contact cheilitis: analysis of 38 cases.

PMID- 25765960
TI  - H2A.Z marks antisense promoters and has positive effects on antisense transcript
      levels in budding yeast.
AB  - BACKGROUND: The histone variant H2A.Z, which has been reported to have both
      activating and repressive effects on gene expression, is known to occupy
      nucleosomes at the 5' ends of protein-coding genes. RESULTS: We now find that
      H2A.Z is also significantly enriched in gene coding regions and at the 3' ends of
      genes in budding yeast, where it co-localises with histone marks associated with
      active promoters. By comparing H2A.Z binding to global gene expression in budding
      yeast strains engineered so that normally unstable transcripts are abundant, we
      show that H2A.Z is required for normal levels of antisense transcripts as well as
      sense ones. High levels of H2A.Z at antisense promoters are associated with
      decreased antisense transcript levels when H2A.Z is deleted, indicating that
      H2A.Z has an activating effect on antisense transcripts. Decreases in antisense
      transcripts affected by H2A.Z are accompanied by increased levels of paired sense
      transcripts. CONCLUSIONS: The effect of H2A.Z on protein coding gene expression
      is a reflection of its importance for normal levels of both sense and antisense
      transcripts.

PMID- 25765962
TI  - How to do a 'roof-top' approach to the supraceliac aorta.

PMID- 25765963
TI  - A health record integrated clinical decision support system to support
      prescriptions of pharmaceutical drugs in patients with reduced renal function:
      design, development and proof of concept.
AB  - OBJECTIVES: To develop and verify proof of concept for a clinical decision
      support system (CDSS) to support prescriptions of pharmaceutical drugs in
      patients with reduced renal function, integrated in an electronic health record
      system (EHR) used in both hospitals and primary care. METHODS: A pilot study in
      one geriatric clinic, one internal medicine admission ward and two outpatient
      healthcare centers was evaluated with a questionnaire focusing on the usefulness
      of the CDSS. The usage of the system was followed in a log. RESULTS: The CDSS is
      considered to increase the attention on patients with impaired renal function,
      provides a better understanding of dosing and is time saving. The calculated
      glomerular filtration rate (eGFR) and the dosing recommendation classification
      were perceived useful while the recommendation texts and background had been used
      to a lesser extent. DISCUSSION: Few previous systems are used in primary care and
      cover this number of drugs. The global assessment of the CDSS scored high but
      some elements were used to a limited extent possibly due to accessibility or that
      texts were considered difficult to absorb. Choosing a formula for the calculation
      of eGFR in a CDSS may be problematic. CONCLUSIONS: A real-time CDSS to support
      kidney-related drug prescribing in both hospital and outpatient settings is
      valuable to the physicians. It has the potential to improve quality of drug
      prescribing by increasing the attention on patients with renal insufficiency and
      the knowledge of their drug dosing.

PMID- 25765964
TI  - Salmonella flagellin is a potent carrier-adjuvant for peptide conjugate to induce
      peptide-specific antibody response in mice.
AB  - As an agonist to innate immune system, Salmonella flagellin has been proven to be
      a potent adjuvant either admixed or genetically fused with antigens and applied
      to a variety of vaccines against infectious diseases. However, relatively little
      is known about its carrier-adjuvant effect for conjugate vaccine. Conjugation is
      an effective approach often used to make haptens such as some peptides and
      polysaccharides immunogenic and in some cases used to make poor immunogens more
      immunogenic. In the current study, Salmonella flagellin was tested for its
      carrier-adjuvant effect in a peptide conjugation. The recombinant Salmonella
      flagellin (rFliC) purified from Escherichia coli was firstly modified by
      maleimide groups, then coupled with a synthetic peptide (EXP153:CDNNLVSGP) that
      is a B-cell epitope derived from Plasmodium falciparum exported protein-1 to
      generate the conjugate of EXP153-rFliC. Bioactivity assay showed that both
      chemical modification and conjugation did not apparently impair the TLR5-ligand
      activity of rFliC. EXP153-rFliC was used to immunize BALB/c mice via subcutaneous
      route, and the sera obtained from immunized mice were examined by ELISA and IFA.
      While no detectable antibody responses were induced by the peptide admixed with
      rFliC, the robust peptide-specific antibody responses were observed in mice
      immunized with the peptide conjugated to rFliC in the absence of any additional
      adjuvant. The immune sera induced by the conjugate recognized the native protein
      of malaria parasite. The data obtained from this study demonstrate the carrier
      adjuvant activity of Salmonella flagellin in peptide conjugate immunization and
      indicate its promising application for conjugate vaccine research and
      development. 

PMID- 25765965
TI  - Variation of growth in the production of the BCG vaccine and the association with
      the immune response. An observational study within a randomised trial.
AB  - INTRODUCTION: Bacille Calmette-Guerin (BCG) vaccine has beneficial non-specific
      effects on overall survival. After BCG vaccination, positive PPD response and
      scar formation are associated with increased survival. During a trial randomising
      low-birth-weight neonates to BCG at birth or the usual delayed BCG, the
      manufacturer of the BCG vaccine experienced a period with relatively slow growth
      rate of the BCG. We investigated the association between growth rate of BCG when
      manufacturing the vaccine and its capability to induce immune responses in vivo
      and in vitro. METHODS: 1633 neonates were randomised to BCG at birth and examined
      for scar at 12 months; a subgroup was tested for PPD response at 2 and 6 months.
      The BCG batches from the Slow growth period were compared with the precedent and
      subsequent Normal growth batches with regard to prevalence and size of BCG scar
      and PPD response. We also tested the effect of batches on in vitro cytokine
      responses. RESULTS: At 12 months, the Slow growth batches were associated with
      higher BCG scar prevalence (98.2%) than the precedent batches (92.3%, p=0.01) but
      the prevalence remained high after return to normal growth (98.8%, p=0.52). The
      Slow growth batches were associated with larger scar size (5.0mm) than precedent
      (4.4mm, p<0.01) and subsequent batches (4.8mm, p=0.03). Compared with Normal
      growth batches, the Slow growth batches were associated with a higher prevalence
      of positive PPD responses, and among PPD positive children, a larger PPD reaction
      (geometric mean ratio: 1.40 (1.20-1.63)) at 2 months. In response to secondary
      heterologous stimulation, monocytes primed with Slow growth batches induced
      higher IL-6 (p=0.03) and TNF-alpha responses (p=0.03) compared with Normal growth
      batches. CONCLUSION: The study indicates that variations in the production of BCG
      vaccine may influence important immunological effects of the vaccine. TRIAL
      REGISTRATION: clinicaltrials.gov (NCT00625482).

PMID- 25765966
TI  - Immunogenicity and safety of a combined measles, mumps, rubella and varicella
      live vaccine (ProQuad (r)) administered concomitantly with a booster dose of a
      hexavalent vaccine in 12-23-month-old infants.
AB  - BACKGROUND: Concomitant administration of vaccines can facilitate vaccination
      uptake, provided that no clinically significant effect on either vaccine is
      identified. We investigated the concomitant administration, during the second
      year of life, of one dose of the combined measles, mumps, rubella and varicella
      vaccine (ProQuad((r))) with a booster dose of a hexavalent vaccine. METHODS: In
      this multicentre, open-label study, participants were randomized to 3 groups:
      Group 1, concomitant administration of one dose of ProQuad((r)) and a booster of
      hexavalent vaccine; Group 2, one dose of ProQuad((r)) alone; Group 3, a booster
      dose of hexavalent vaccine alone. Two serum samples were collected, within 7 days
      prior to vaccination and Days 42-56 post-vaccination for antibody testing.
      RESULTS: Antibody response rates to measles, mumps, rubella, varicella, hepatitis
      B and Haemophilus influenzae type b following concomitant administration of
      ProQuad((r)) and hexavalent vaccine were non-inferior compared with those
      following the individual vaccines. Antibody response rates to these antigens were
      all >95% in all groups. Antibody titres for the pertussis antigens following
      concomitant administration were also non-inferior to those following the
      individual vaccines. Antibody titres for the other valences were numerically
      comparable between groups with the exception of hepatitis B, Haemophilus
      influenzae type b, tetanus and poliomyelitis, which were higher in the
      concomitant than in the non-concomitant groups. The safety profiles of each
      vaccination regimen were comparable, with the exception of solicited ProQuad((r))
      related injection-site reactions (Days 0-4), which occurred more frequently in
      the concomitant than in the non-concomitant groups. CONCLUSION: These
      immunogenicity data support the concomitant administration of ProQuad((r)) with a
      hexavalent vaccine. The safety profile of concomitant ProQuad((r)) and hexavalent
      vaccination was also in line with that of the individual Summaries of Product
      Characteristics.

PMID- 25765967
TI  - The novel adjuvant dmLT promotes dose sparing, mucosal immunity and longevity of
      antibody responses to the inactivated polio vaccine in a murine model.
AB  - One option for achieving global polio eradication is to replace the oral
      poliovirus vaccine (OPV), which has the risk of reversion to wild-type virulence,
      with the inactivated poliovirus vaccine (IPV) vaccine. Adjuvants and alternate
      routes of immunization are promising options that may reduce antigen dose in IPV
      vaccinations, potentially allowing dose sparing and cost savings. Use of
      adjuvants and alternate routes of immunization could also help promote mucosal
      immunity, potentially mimicking the protection against intestinal virus shedding
      seen with OPV. In the current study, we examined the impact of combining the
      novel adjuvant dmLT with trivalent IPV for dose sparing, induction of mucosal
      immunity and increasing longevity of anti-poliovirus (PV) responses in a mouse
      model following either intradermal (ID) or intramuscular (IM) delivery. We found
      that non-adjuvanted ID delivery was not superior to IM delivery for fractional
      dose sparing, but was associated with development of mucosal immunity.
      Vaccination with IPV+dmLT promoted serum anti-PV neutralizing antibodies with
      fractional IPV doses by either IM or ID delivery, achieving at least five-fold
      dose sparing above non-adjuvanted fractional doses. These responses were most
      noticeable with the PV1 component of the trivalent vaccine. dmLT also promoted
      germinal center formation and longevity of serum anti-PV neutralizing titers.
      Lastly, dmLT enhanced mucosal immunity, as defined by fecal and intestinal anti
      PV IgA secretion, when included in IPV immunization by ID or IM delivery. These
      studies demonstrate that dmLT is an effective adjuvant for either IM or ID
      delivery of IPV. Inclusion of dmLT in IPV immunizations allows antigen dose
      sparing and enhances mucosal immunity and longevity of anti-PV responses. 

PMID- 25765968
TI  - Plasmodium vivax gametocyte proteins, Pvs48/45 and Pvs47, induce transmission
      reducing antibodies by DNA immunization.
AB  - Malaria transmission-blocking vaccines (TBV) aim to interfere with the
      development of the malaria parasite in the mosquito vector, and thus prevent
      spread of transmission in a community. To date three TBV candidates have been
      identified in Plasmodium vivax; namely, the gametocyte/gamete protein Pvs230, and
      the ookinete surface proteins Pvs25 and Pvs28. The Plasmodium falciparum
      gametocyte/gamete stage proteins Pfs48/45 and Pfs47 have been studied as TBV
      candidates, and Pfs48/45 shown to induce transmission-blocking antibodies, but
      the candidacy of their orthologs in P. vivax, Pvs48/45 (PVX_083235) and Pvs47
      (PVX_083240), for vivax TBV have not been tested. Herein we investigated whether
      targeting Pvs48/45 and Pvs47 can inhibit parasite transmission to mosquitoes,
      using P. vivax isolates obtained in Thailand. Mouse antisera directed against the
      products from plasmids expressing Pvs48/45 and Pvs47 detected proteins of
      approximately 45- and 40-kDa, respectively, in the P. vivax gametocyte lysate, by
      Western blot analysis under non-reducing conditions. In immunofluorescence assays
      Pvs48/45 was detected predominantly on the surface and Pvs47 was detected in the
      cytoplasm of gametocytes. Membrane feeding transmission assays demonstrated that
      anti-Pvs48/45 and -Pvs47 mouse sera significantly reduced the number of P. vivax
      oocysts developing in the mosquito midgut. Limited amino acid polymorphism of
      these proteins was observed among 27 P. vivax isolates obtained from Thailand,
      Vanuatu, and Colombia; suggesting that polymorphism may not be an impediment for
      the utilization of Pvs48/45 and Pvs47 as TBV antigens. In one Thai isolate we
      found that the fourth cysteine residue in the Pvs47 cysteine-rich domain (CRD)
      III (amino acid position 337) is substituted to phenylalanine. However,
      antibodies targeting Pvs47 CRDI-III showed a significant transmission-reducing
      activity against this isolate, suggesting that this substitution in Pvs47 was not
      critical for recognition by the generated antibodies. In conclusion, our results
      indicate that Pvs48/45 and Pvs47 are potential transmission-blocking vaccine
      candidates of P. vivax. 

PMID- 25765969
TI  - A review of the global pesticide legislation and the scale of challenge in
      reaching the global harmonization of food safety standards.
AB  - Pesticide use is important in agriculture to protect crops and improve
      productivity. However, pesticides have the potential to cause adverse human
      health or environmental effects, depending on exposure levels. This review
      examines existing pesticide legislation worldwide, focusing on the level of
      harmonization and impacts of differing legislation on food safety and trade.
      Pesticide legislation varies greatly worldwide, because countries have different
      requirements, guidelines, and legal limits for plant protection. Developed
      nations have more stringent regulations than developing countries, which lack the
      resources and expertise to adequately implement and enforce legislation. Global
      differences in pesticide legislation act as a technical barrier to trade.
      International parties such as the European Union (EU), Codex Alimentarius
      Commission (Codex), and North American Free Trade Agreement (NAFTA) have
      attempted to harmonize pesticide legislation by providing maximum residue limits
      (MRLs), but globally these limits remain variable. Globally harmonized pesticide
      standards would serve to increase productivity, profits, and trade and also
      enhance the ability to protect public health and the environment.

PMID- 25765970
TI  - Liquid phase exfoliation and crumpling of inorganic nanosheets.
AB  - Here we demonstrate through experiment and simulation the polymer-assisted
      dispersion of inorganic 2D layered nanomaterials such as boron nitride nanosheets
      (BNNSs), molybdenum disulfide nanosheets (MoS2), and tungsten disulfide
      nanosheets (WS2), and we show that spray drying can be used to alter such
      nanosheets into a crumpled morphology. Our data indicate that
      polyvinylpyrrolidone (PVP) can act as a dispersant for the inorganic 2D layered
      nanomaterials in water and a range of organic solvents; the effectiveness of our
      dispersion process was characterized by UV-vis spectroscopy, microscopy and
      dynamic light scattering. Molecular dynamics simulations confirm that PVP readily
      physisorbs to BNNS surfaces. Collectively, these results indicate that PVP acts
      as a general dispersant for nanosheets. Finally, a rapid spray drying technique
      was utilized to convert these 2D dispersed nanosheets into 3D crumpled
      nanosheets; this is the first report of 3D crumpled inorganic nanosheets of any
      kind. Electron microscopy images confirm that the crumpled nanosheets (1-2 MUm in
      diameter) show a distinctive morphology with dimples on the surface as opposed to
      a wrinkled, compressed surface, which matches earlier simulation results. These
      results demonstrate the possibility of scalable production of inorganic
      nanosheets with tailored morphology. 

PMID- 25765971
TI  - Chronic drought stress reduced but not protected Shantung maple (Acer truncatum
      Bunge) from adverse effects of ozone (O3) on growth and physiology in the suburb
      of Beijing, China.
AB  - A two-year experiment exposing Acer truncatum Bunge seedlings to elevated ozone
      (O3) concentrations above ambient air (AO) and drought stress (DS) was carried
      out using open-top chambers (OTCs) in a suburb of Beijing in north China in 2012
      2013. The results suggested that AO and DS had both significantly reduced leaf
      mass area (LMA), stomatal conductance (Gs), light saturated photosynthetic rate
      (Asat) as well as above and below ground biomass at the end of the experiment. It
      appeared that while drought stress mitigated the expression of foliar injury,
      LMA, leaf photosynthetic pigments, height growth and basal diameter, due to
      limited carbon fixation, the O3 - induced reductions in Asat, Gs and total
      biomass were enhanced 23.7%. 15.5% and 8.1% respectively. These data suggest that
      when the whole plant was considered that drought under the conditions of this
      experiment did not protect the Shantung maple seedlings from the effects of O3. 

PMID- 25765972
TI  - Linking biochemical perturbations in tissues of the African catfish to the
      presence of polycyclic aromatic hydrocarbons in Ovia River, Niger Delta region.
AB  - Petroleum hydrocarbons including polycyclic aromatic hydrocarbons (PAHs) are a
      pollution issue in the Niger Delta region due to oil industry activities. PAHs
      were measured in the water column of the Ovia River with concentrations ranging
      from 0.1 to 1055.6 ng L(-1). Attenuated total reflection Fourier-transform
      infrared (ATR-FTIR) spectroscopy detected alterations in tissues of the African
      catfish (Heterobranchus bidorsalis) from the region showed varying degrees of
      statistically significant (P<0.0001, P<0.001, P<0.05) changes to absorption band
      areas and shifts in centroid positions of peaks. Alteration patterns were similar
      to those induced by benzo[a]pyrene in MCF-7 cells. These findings have potential
      health implications for resident local communities as H. bidorsalis constitutes a
      key nutritional source. The study provides supporting evidence for the
      sensitivity of infrared spectroscopy in environmental studies and supports their
      potential application in biomonitoring. 

PMID- 25765973
TI  - Stress Experienced by Obstetrics and Gynecology Residents during Planned
      Laparoscopy: A Prospective, Multicentric, Observational, Blinded, and Comparative
      Study.
AB  - AIMS: To describe heart rate (HR) variations in surgical residents during
      laparoscopy and to assess their intraoperative stress. METHODS: We performed a
      prospective, multicentric, observational, blinded, and comparative analysis of
      the HR in 75 obstetrics and gynecology residents during planned laparoscopy for
      infertility in five teaching hospitals with assisted reproductive technology
      centers. The surgical residents had neither heart disease nor were under medical
      treatment or using tobacco or drugs. We describe HR variations at 9 preselected
      operative steps using real-time noninvasive measures of the HR during
      laparoscopy. RESULTS: Residents performed 124 laparoscopies for unexplained
      infertility. Their HR increased significantly during the introduction of the
      Palmer needle, umbilical port and second port, and during abdominopelvic
      exploration and dye test compared to the baseline HR, the HR after hand washing,
      at the end of surgery and during skin suture (91.6 +/- 1.9, 104.8 +/- 2.3, 95.3
      +/- 2.2, 93.7 +/- 2.5, 90.7 +/- 1.7 vs. 83.2 +/- 1.6, 88.6 +/- 1.9, 87.4 +/- 2.1,
      88.2 +/- 1.9 bpm, respectively, p < 0.02). CONCLUSION: Our results point to a
      potential stress for the surgeon assessed by HR variations during planned
      laparoscopy compared to the baseline HR before surgery. This 'static' stress can
      be repeated on the same day.

PMID- 25765974
TI  - Luminescent ruthenium(II) complex bearing bipyridine and N-heterocyclic carbene
      based C?N?C pincer ligand for live-cell imaging of endocytosis.
AB  - Luminescent ruthenium(II)-cyanide complex with N-heterocyclic carbene pincer
      ligand C(?)N(?)C = 2,6-bis(1-butylimidazol-2-ylidene)pyridine and 2,2'-bipyridine
      (bpy) shows minimal cytotoxicity to both human breast carcinoma cell (MCF-7) and
      human retinal pigmented epithelium cell (RPE) in a wide range of concentration
      (0.1-500 MUM), and can be used for the luminescent imaging of endocytosis of the
      complex in these cells.

PMID- 25765975
TI  - [Template selection by replication protein of tobacco mosaic virus].
AB  - Replication proteins of eukaryotic positive-strand RNA viruses specifically
      recognize the genomic RNA as replication template, recruit them to the surfaces
      of intracellular membranes, and form replication complexes. We recently revealed
      that tobacco mosaic virus (TMV) replication protein cotranslationally binds 5'
      untranslated region (UTR) of the genomic RNA, and that a full-length replication
      protein cannot posttranslationally bind TMV RNA in trans. This result provides a
      mechanistic explanation for the previously reported property of TMV replication
      protein that it selects replication template preferentially in cis. We also found
      that the binding of the replication protein to the 5' UTR prevents further
      translation of the genomic RNA. Fatal collision between translating ribosomes and
      negative-strand RNA-synthesizing polymerases on the genomic RNA is thus avoided. 

PMID- 25765976
TI  - [Cryphonectria parasitica as a host of fungal viruses: a tool useful to unravel
      the mycovirus world].
AB  - There appear to be over a million of fungal species including those that have
      been unidentified and unreported, where a variety of viruses make a world as
      well. Studies on a very small number of them conducted during the last two
      decades demonstrated the infectivity of fungal viruses that had previously been
      assumed to be inheritable, indigenus and non-infectious. Also, great technical
      advances were achieved. The chest blight fungus (Cryphonectria parasitica), a
      phytopathogenic ascomycetous fungus, has emerged as a model filamentous fungus
      for fungal virology. The genome sequence with annotations, albeit not thorough,
      many useful research tools, and gene manipulation technologies are available for
      this fungus. Importantly, C. parasitica can support replication of homologous
      viruses naturally infecting it, in addition to heterologous viruses infecting
      another plant pathogenic fungus, Rosellinia necatrix taxonomically belonging to a
      different order. In this article, I overview general properties of fungal viruses
      and advantages of the chestnut blight fungus as a mycovirus host. Furthermore, I
      introduce two recent studies carried out using this fungal host:''Defective
      interfering RNA and RNA silencing that regulate the replication of a
      partitivirus'' and'' RNA silencing and RNA recombination''. 

PMID- 25765977
TI  - [Epidemiological and basic research activity targeting polyomaviruses].
AB  - Recently, the family Polyomaviridae was classified as 3 genera, such as
      Orthopolyomavirus, Wukipolyomavirus which contain mammalian polyomaviruses and
      Avipolyomavirus which only contain avian polyomaviruses. We have recently
      isolated novel polyomaviruses, including Mastomys Polyoamvirus (MasPyV) and
      Vervet monkey Polyoamvirus-1 (VmPyV-1) by epidemiological activities and examined
      functions of their encoding proteins. In addition, we have been investigating the
      mechanisms of replication of human polyomavirus, JC polyomavirus (JCPyV). We
      recently obtained the results of function of JCVPyV-encoding proteins, including
      early protein (Large T antigen) and late proteins (VP1 and Agno). In this review,
      we summarized the data of our basic research activities. 

PMID- 25765978
TI  - [Development of new therapies targeting human papillomavirus molecules].
AB  - High-risk HPV E6 and E7 oncogenes are an ideal targeting gene for treatment of
      cervical cancer. In this paper, we introduce researches on cancer-immunotherapy
      targeting HPV E7 through mucosal immunity and E6/E7-targeting siRNA therapy using
      PEGylated polymeric micelles. Therapeutic HPV vaccine has also attracted
      attention as a cancer immunotherapy agent. We have found homing of Integrin beta7
      positive intestinal mucosal lymphocyte on the cervical mucosa. In this study, we
      generated a novel therapeutic vaccine; an HPV E7-expressing Lactobacillus casei
      (LacE7) to induce anti-HPV cellular immunity directly to intestinal mucosa.
      Cervical lymphocytes (CxLs) and peripheral blood mononuclear cells (PBMCs) were
      counted E7 specific INFgamma-producing cells (E7 cell-mediated immune responses:
      E7-CMI) by ELISPOT assay. We confirmed induction of anti-E7 IFNgamma-producing
      cells in the cervix lymphocytes obtained from these patients. E6/E7 siRNA therapy
      requires a delivery system for its systemic intravenous administration. We here
      demonstrated that intravenous injection of HPV16 or 18 E6/E7 siRNA polymeric
      micelles suppressed excellently an increase in size of subcutaneous tumor formed
      by SiHa or HeLa cell, respectively. Our drug-delivery technology using polymeric
      micelles enabled the successful systemic administration of siRNA to exhibit anti
      tumor effect. 

PMID- 25765979
TI  - [Role of tumor-derived secretary small RNAs in EBV related lymphoma].
AB  - EB virus (EBV) is associated with heterogeneous lymphomas. In these lymphomas
      EBV+ lymphoma cells are embedded in non-neoplastic bystanders: B and T cells,
      macrophages. Without these bystander cells, the lymphoma cells are incapable of
      being engrafted in immunodeficient mice. In this context, the bystanders are
      tumor-supportive "inflammatory niche". Recently, EBV-infected cells produce
      exosomes that contain EBV specifically encoded miRNAs (EBV-miRNAs). Accordingly,
      we hypothesized that exosomal EBV-miRNAs might redirect tumor surrounding immune
      cells from tumor reactive into tumor-supportive "inflammatory niche". The EBV
      miRNAs in the exosome secreted from EBV positive lymphoma cells significantly
      influenced on monocyte/macrophage Mo/Mf in inducing CD69, IL-10, and TNF,
      suggesting that EBV-miRNAs might polarize Mo/Mf into tumor associated Mf (TAM).
      EBV-miRNAs were required to develop lymphoproliferative disease (LPD) in vivo
      mouse model. Moreover, when Mfs were depleted by clodronate liposome, EBV
      positive tumor cells disappeared. These results suggest that lymphoma-derived
      secretary EBV-miRNAs regulate Mo/Mf to support the lymphoma survival or
      development. Most importantly, exosomal EBV-miRNAs derived from the lymphoma
      cells were transferred to Mf in human EBV+ lymphoma samples, which showed
      correlation with prognosis. 

PMID- 25765980
TI  - [Molecular mechanisms of Epstein-Barr virus-mediated carcinogeneis].
AB  - Epstein-Barr virus (EBV), a ubiquitous human double stranded DNA virus, is
      associated with a variety of malignancies including Burkitt's lymphoma, Hodgkin's
      lymphoma, nasopharyngeal carcinoma (NPC) and gastric carcinoma (GC). These EBV
      associated cancers are characterized by the proliferation of monoclonal EBV
      infected cells, and viral gene expression in these cells is limited to a subset
      of latent genes, indicating that EBV latent genes contribute to carcinogenesis.
      Here I describe the mechanisms of carcinogenesis by EBV, focusing on the function
      of two EBV latent gens, latent membrane protein 2A (LMP2A) and EBV-encoded small
      RNA (EBER). LMP2A, which is known to mimic the B cell receptor (BCR) signaling,
      has been reported to contribute to malignant lymphoma development through the
      modulation of immune signals. Also, it has been demonstrated that LMP2A-mediated
      intracellular signaling plays significant roles in epithelial carcinogenesis. On
      the other hand, it has been demonstrated that EBER, which is expected to form
      double stranded RNA (dsRNA) structure, triggers a signal transduction from host
      viral RNA sensors RIG-I and TLR3. Activation of innate immune signals by EBER has
      been reported to contribute to the pathogenesis of EBV-associated diseases,
      including cancers.

PMID- 25765981
TI  - [Regulation of human papillomavirus (HPV) genome replication in the viral life
      cycle and its association with the viral persistence and cancer development].
AB  - High-risk human papillomavirus (HR-HPV) infections account for more than 5% of
      all cancers (11% in women) such as cervical cancer worldwide. HPVs infect to
      basal cells of the stratified squamous epithelium and establish persistent
      infection within the basal compartment. HR-HPV infections can persist more than a
      decade, leading to development of cancers. The life cycle of HPVs is tightly
      associated with the differentiation processes of the stratified squamous
      epithelium; the replication of the viral genome and the expression of the viral
      genes are strictly regulated depending on differentiation of the host
      keratinocytes. The viral genome is transiently amplified immediately following
      infection and then maintained at constant copy numbers in the basal cells. In
      terminally differentiating keratinocytes, the viral genome is drastically
      amplified. However, molecular mechanisms underlying switching these three stages
      of viral genome replication in the viral life cycle are poorly understood.
      Recently, it has become evident that DNA damage response pathways are involved in
      the regulation of HPV genome replication. In this review, we would like to
      introduce recent findings describing the associations of DNA damage response with
      HPV genome replication. 

PMID- 25765982
TI  - [History of resaerch on Epstein-Barr virus--target cells of infection, and
      disease].
AB  - Half a century has passed since Epstein-Barr virus (EBV) particles were isolated
      from the cultured lymphoblasts of Burkitt lymphoma. During the period, molecular
      biology, hematology/immunology, and transplantation medicine made amazing
      progress, that clarified the mode of infection and pathophysiology of the virus
      in human diseases. Research strategies on the relationship between EBV and human
      have expanded to the epidemiology, structures and functions of both genomes,
      regulatory genes including microRNA, and the nature of epigenetics. Although no
      animal models of EBV infection long hampered the completion of in vivo
      experiments, humanized mice have broken through a barrier of in vitro study on
      EBV-infected cell lines. Our understanding of the life cycle of EBV has continued
      to deepen about the infection via the CD21 receptor expressed on B cells, the
      latency, reactivation/reinfection, and transformation, and also the dynamics of T
      cell immune response and the intracellular immunosurveillance beyond acquired and
      innate immunity. On the other hand, the disease entity of life-threatening
      lymphoproliferative disease of EBV-infected T cells or NK cells is on
      controversial. The other parts of this special issue include the recent topics of
      the basic and clinical researches of EBV as the oncogenic virus. Then, we
      herewith overview the research history of EBV with special reference to the
      infected cells and host immune responses in EBV-associated diseases. 

PMID- 25765983
TI  - [Genome editing with programmable site-specific nucleases].
AB  - Genome editing is a cutting-edge technology that enables to modify the target
      gene using programmable site-specific nucleases, such as TALENs and CRISPR/Cas9.
      Currently, cell and animal models of human diseases have been competitively
      created throughout the world, because genome editing technology paved the way for
      genetic modifications even in cells and organisms that had been difficult to
      manipulate the genome. In this review, we introduce the basic principles and
      current situations of genome editing with programmable nucleases. 

PMID- 25765984
TI  - [Innate immune DNA sensing pathways].
AB  - How the cells triggers the induction of innate immune genes in response to
      nucleic acids derived from microbes, such as DNA viruses, intracellular bacteria,
      and parasites, or self DNA, has not been elucidated fully. We have previously
      shown that an endoplasmic reticulum (ER)-associated multiple transmembrane
      protein, so-called STING (stimulator of interferon genes), functions as an
      essential molecules for triggering DNA-mediated gene induction. STING may
      directly associate with stimulatory ligands, which include DNA, as well as with
      cyclic dinucleotides (CDNs), which are secreted by intracellular bacteria. After
      DNA or CDN stimulation, STING traffics with kinase TBK1 in an autophagic
      signaling complex, from ER to perinuclear endosomal compartments harboring IRF3
      and NF-kappaB. STING may involve in autoinflammatory disease manifested by
      aberrant self-DNA. Understanding of STING function may conceivably lead to the
      development of potent adjuvants for vaccine development or conversely
      therapeutics that could control inflammation aggravated disease. 

PMID- 25765985
TI  - [Lifecycles of EBV and cancer].
AB  - Epstein-Barr virus (EBV) is a member of gamma-herpesvirus, which can cause
      various types of tumor. Coexisting with the host for a long period of time, it
      has evolved unique and sophisticated strategy for survival by taking complicated,
      tactical modes of infection. Such modes include latent and lytic infections, and
      latent state is further categorized into four types. Differences and transitions
      in such lifestyles are significantly associated not only with virus
      amplification, but also with pathology and advancement of the disorders. I here
      review oncogenesis and pathogenesis of EBV-related disorders, especially focusing
      on our recent results on the modes of EBV infection. 

PMID- 25765986
TI  - [Study of pathogenicity of Nipah virus and its vaccine development].
AB  - Nipah virus (NiV), a paramyxovirus, was first discovered in Malaysia in 1998 in
      an outbreak of infection in pigs and humans, and incurred a high fatality rate in
      humans. We established a system that enabled the rescue of replicating NiVs from
      a cloned DNA. Using the system, we analyzed the functions of accessory proteins
      in infected cells and the implications in in vivo pathogenicity. Further, we have
      developed a recombinant measles virus (rMV) vaccine expressing NiV envelope
      glycoproteins, which appeared to be an appropriate to NiV vaccine candidate for
      use in humans. 

PMID- 25765987
TI  - Quantitative multi-spectral oxygen saturation measurements independent of tissue
      optical properties.
AB  - Imaging of tissue oxygenation is important in several applications associated
      with patient care. Optical sensing is commonly applied for assessing oxygen
      saturation but is often restricted to local measurements or else it requires
      spectral and spatial information at the expense of time. Many methods proposed so
      far require assumptions on the properties of measured tissue. In this study we
      investigated a computational method that uses only multispectral information and
      quantitatively computes tissue oxygen saturation independently of tissue optical
      properties. The method is based on linear transformations of measurements in
      three isosbestic points. We investigated the ideal isosbestic point combination
      out of six isosbestic points available for measurement in the visible and near
      infrared region that enable accurate oxygen saturation computation. We
      demonstrate this method on controlled tissue mimicking phantoms having different
      optical properties and validated the measurements using a gas analyzer. A mean
      error of 2.9 +/- 2.8% O2 Sat was achieved. Finally, we performed pilot studies in
      tissues in-vivo by measuring dynamic changes in fingers subjected to vascular
      occlusion, the vasculature of mouse ears and exposed mouse organs.

PMID- 25765988
TI  - Transcriptomic analysis predicts survival and sensitivity to anticancer drugs of
      patients with a pancreatic adenocarcinoma.
AB  - A major impediment to the effective treatment of patients with pancreatic ductal
      adenocarcinoma (PDAC) is the molecular heterogeneity of this disease, which is
      reflected in an equally diverse pattern of clinical outcome and in responses to
      therapies. We developed an efficient strategy in which PDAC samples from 17
      consecutive patients were collected by endoscopic ultrasound-guided fine-needle
      aspiration or surgery and were preserved as breathing tumors by xenografting and
      as a primary culture of epithelial cells. Transcriptomic analysis was performed
      from breathing tumors by an Affymetrix approach. We observed significant
      heterogeneity in the RNA expression profile of tumors. However, the bioinformatic
      analysis of these data was able to discriminate between patients with long- and
      short-term survival corresponding to patients with moderately or poorly
      differentiated PDAC tumors, respectively. Primary culture of cells allowed us to
      analyze their relative sensitivity to anticancer drugs in vitro using a
      chemogram, similar to the antibiogram for microorganisms, establishing an
      individual profile of drug sensitivity. As expected, the response was patient
      dependent. We also found that transcriptomic analysis predicts the sensitivity of
      cells to the five anticancer drugs most frequently used to treat patients with
      PDAC. In conclusion, using this approach, we found that transcriptomic analysis
      could predict the sensitivity to anticancer drugs and the clinical outcome of
      patients with PDAC.

PMID- 25765989
TI  - Comparison of synthetic medium and wastewater used as dilution medium to design
      scalable microbial anodes: Application to food waste treatment.
AB  - The objective was to replace synthetic medium by wastewater as a strategy to
      design low-cost scalable bioanodes. The addition of activated sludge was
      necessary to form primary bioanodes that were then used as the inoculum to form
      the secondary bioanodes. Bioanodes formed in synthetic medium with acetate 10mM
      provided current densities of 21.9+/-2.1A/m(2), while bioanodes formed in
      wastewater gave 10.3+/-0.1A/m(2). The difference was explained in terms of
      biofilm structure, electrochemical kinetics and redox charge content of the
      biofilms. In both media, current densities were straightforwardly correlated with
      the biofilm enrichment in Geobacteraceae but, inside this family, Geobacter
      sulfurreducens and an uncultured Geobacter sp. were dominant in the synthetic
      medium, while growth of another Geobacter sp. was favoured in wastewater.
      Finally, the primary/secondary procedure succeeded in designing bioanodes to
      treat food wastes by using wastewater as dilution medium, with current densities
      of 7+/-1.1A/m(2). 

PMID- 25765990
TI  - Young children retain fast mapped object labels better than shape, color, and
      texture words.
AB  - We compared short- and long-term retention of fast mapped color, shape, and
      texture words as well as object labels. In an exposure session, 354 3- and 4-year
      old children were shown a set of two familiar and three novel stimuli. One of the
      novel stimuli was labeled with a new object label, color, shape, or texture word.
      Retention of the mapping between the new word and the novel object or property
      was measured either 5 min or 1 week later. After 5 min, retention was
      significantly above chance in all conditions. However, after 1 week, only the
      mappings for object labels were retained above chance levels. Our findings
      suggest that fast mapped object labels are retained long term better than color,
      shape, and texture words. The results also highlight the importance of comparing
      short- and long-term retention when studying children's word learning.

PMID- 25765992
TI  - Plasticity in the growth of the chick eye: emmetropization achieved by alternate
      morphologies.
AB  - Both refractive properties of the eyes and ambient light conditions affect
      emmetropization during growth. Exposure to constant light flattens the cornea
      making chicks hyperopic. To discover whether and how growing chick eyes restore
      emmetropia after exposure to constant light (CL) for 3, 7, or 11weeks, we
      returned chicks to normal (N) conditions with 12h. of light alternating with 12h.
      of darkness (designated the "R", or recovery, condition) for total periods of 4,
      7, 11, or 17weeks. The two control groups were raised in CL conditions or raised
      in N conditions for the same length of time. We measured anterior chamber depths
      and lens thicknesses with an A-scan ultrasound machine. We measured corneal
      curvatures with an eight-axis keratometer, and refractions with conventional
      retinoscopy. We estimated differences in optical powers of CL, R and N chicks of
      identical age by constructing ray-tracing models using the above measurements and
      age-adjusted normal lens curvatures. We also computed the sensitivity of focus
      for small perturbations of the above optical parameters. Full refractive recovery
      from CL effects always occurred. Hyperopic refractive errors were absent when R
      chicks were returned to N for as little as 1week after 3weeks CL treatment. In R
      chicks exposed to CL for 11weeks and returned to N, axial lengths, vitreous
      chamber depths and radii of corneal curvatures did not return to normal, although
      their refractions did. While R chicks can usually recover emmetropia, after long
      periods of exposure to CL, they cannot recover normal ocular morphology.
      Emmetropization following CL exposure is achieved primarily by adjusting the
      relationship between corneal curvature and axial length, resulting in normal
      refractions. 

PMID- 25765991
TI  - Genetic variants in root architecture-related genes in a Glycine soja accession,
      a potential resource to improve cultivated soybean.
AB  - BACKGROUND: Root system architecture is important for water acquisition and
      nutrient acquisition for all crops. In soybean breeding programs, wild soybean
      alleles have been used successfully to enhance yield and seed composition traits,
      but have never been investigated to improve root system architecture. Therefore,
      in this study, high-density single-feature polymorphic markers and simple
      sequence repeats were used to map quantitative trait loci (QTLs) governing root
      system architecture in an inter-specific soybean mapping population developed
      from a cross between Glycine max and Glycine soja. RESULTS: Wild and cultivated
      soybean both contributed alleles towards significant additive large effect QTLs
      on chromosome 6 and 7 for a longer total root length and root distribution,
      respectively. Epistatic effect QTLs were also identified for taproot length,
      average diameter, and root distribution. These root traits will influence the
      water and nutrient uptake in soybean. Two cell division-related genes (D type
      cyclin and auxin efflux carrier protein) with insertion/deletion variations might
      contribute to the shorter root phenotypes observed in G. soja compared with
      cultivated soybean. Based on the location of the QTLs and sequence information
      from a second G. soja accession, three genes (slow anion channel associated 1
      like, Auxin responsive NEDD8-activating complex and peroxidase), each with a non
      synonymous single nucleotide polymorphism mutation were identified, which may
      also contribute to changes in root architecture in the cultivated soybean. In
      addition, Apoptosis inhibitor 5-like on chromosome 7 and slow anion channel
      associated 1-like on chromosome 15 had epistatic interactions for taproot length
      QTLs in soybean. CONCLUSION: Rare alleles from a G. soja accession are expected
      to enhance our understanding of the genetic components involved in root
      architecture traits, and could be combined to improve root system and drought
      adaptation in soybean.

PMID- 25765993
TI  - Principal component analysis of the memory load effect in a change detection
      task.
AB  - Previous research using the change detection task has found little or no
      relationship between P3 amplitude and working memory load. This contrasts with
      findings from other paradigms that indicate a decrease in P3 amplitude with
      increases in working memory load. We adopted a principal component analysis
      strategy to resolve this discrepancy. After ERPs were decomposed, the P3
      component decreased in amplitude when the memory load increased. Its amplitude
      was also associated with individuals' working memory capacity. In conclusion, P3
      plays a critical role in change detection task as it does in other working memory
      tasks. 

PMID- 25765994
TI  - CD40 ligand exhibits a direct antiviral effect on Herpes Simplex Virus type-1
      infection via a PI3K-dependent, autophagy-independent mechanism.
AB  - The interaction between CD40 and its ligand, CD40L/CD154, is crucial for the
      efficient initiation and regulation of immune responses against viruses. Herpes
      Simplex Virus type-1 (HSV-1) is a neurotropic virus capable of manipulating host
      responses and exploiting host proteins to establish productive infection. Herein
      we have examined the impact of CD40L-mediated CD40 activation on HSV-1
      replication in U2OS cells stably expressing the CD40 receptor. Treatment of these
      cells with CD40L significantly reduced the HSV-1 progeny virus compared to non
      treated cells. The activation of CD40 signaling did not affect the binding of HSV
      1 virions on the cell surface but rather delayed the translocation of VP16 to the
      nucleus, affecting all stages of viral life cycle. Using pharmacological
      inhibitors and RNAi we show that inhibition of PI3 kinase but not autophagy
      reverses the effects of CD40L on HSV-1 replication. Collectively, these data
      demonstrate that CD40 activation exerts a direct inhibitory effect on HSV-1,
      initiating from the very early stages of the infection by exploiting PI3 kinase
      dependent but autophagy-independent mechanisms. 

PMID- 25765995
TI  - Cerebral lesions on 7 tesla MRI in patients with sickle cell anemia.
AB  - BACKGROUND: Patients with sickle cell anemia (SCA) are at a high risk to develop
      cerebral damage. Most common are silent cerebral infarctions (SCIs), visible as
      white matter hyperintensities (WMHs) on MRI in a patient without neurological
      deficits. The etiology of SCIs remains largely unclear. In addition, patients are
      at an increased risk for overt stroke, which is associated with large vessel
      disease. This classification based on the presence or absence of neurological
      deficits may not be the most fitting for research purposes, as it does not match
      the different underlying pathology. A classification based on imaging findings
      may therefore be a more straightforward approach for research purposes. We
      explored the feasibility to identify imaging features of SCIs in young,
      asymptomatic patients with SCA using ultra high-field 7 Tesla (7T) MRI. 7T MRI
      has a high resolution, which offers a unique chance to investigate small
      subclinical brain lesions in detail. To explore the superiority of 7T in
      identifying imaging abnormalities, we compared our results with 3T MRI. METHODS:
      Ten young, neurologically asymptomatic patients with SCA underwent 7T and 3T MRI;
      10 healthy, age-matched controls underwent 7T MRI. We used existing neuroimaging
      standards to classify the brain lesions. We scored 7T and 3T scans separately,
      blinded for all other results. RESULTS: Using 7T MRI, we identified more patients
      with intracerebral lesions (9/10 vs. 5/10), a higher total count of WMHs (203 vs.
      190, p = 0.016) and more lacunes (5 vs. 4) compared to 3T MRI. Abnormalities seen
      on 7T, which could not be identified on 3T, were cortical hyperintensities (in
      3/10) and a different aspect of irregular WMHs, closely associated with cortical
      hyperintensities in a patient with large vessel stenosis. In 7 controls, a total
      of 13 WMHs were present. CONCLUSION: Using 7T MRI, we identified more
      intracerebral lesions compared to 3T, and found several abnormalities not visible
      on 3T. 7T MRI in SCA seems of particular interest to study the cortical
      involvement and the relation between WMHs and the cortex. We found some imaging
      features that are thought to be representative for small vessel disease,
      including WMHs, lacunes and prominent perivascular spaces; to understand whether
      small vessel disease plays a role in SCA requires further research.

PMID- 25765997
TI  - Early experience with laparoscopic lavage in acute complicated diverticulitis.
AB  - BACKGROUND: Contemporary surgical management of complicated diverticulitis is
      controversial. Traditionally, the gold standard has been resection and colostomy,
      but recently peritoneal lavage and drainage without resection in cases of
      purulent peritonitis have been suggested. This study aims to review our initial
      experience with laparoscopic peritoneal lavage for complicated diverticulitis.
      METHODS: Retrospective review of all patients who underwent emergent peritoneal
      lavage and drainage for acute complicated diverticulitis. RESULTS: Five-hundred
      thirty-eight patients admitted for acute diverticulitis between 2007 and 2012
      were recorded in the database. Thirty seven underwent emergent surgery of which
      10 had peritoneal lavage and drainage without colonic resection for complicated
      diverticulitis causing peritonitis. Peritoneal lavage and drainage resulted in
      the resolution of acute symptoms in all cases. In long-term follow-up, 3 (30%)
      patients required elective resection owing to symptomatic disease, two of these
      due to recurrent diverticulitis, and one owing to complicated fistula following
      the procedure. CONCLUSION: Peritoneal lavage is a feasible option for complicated
      diverticulitis with purulent non-fecal peritonitis, but a significant portion of
      the patients may require elective resection. Comparative studies with emergent
      resection are needed to determine the role of peritoneal lavage in complicated
      diverticulitis.

PMID- 25765996
TI  - Genomic correlates of recombination rate and its variability across eight
      recombination maps in the western honey bee (Apis mellifera L.).
AB  - BACKGROUND: Meiotic recombination has traditionally been explained based on the
      structural requirement to stabilize homologous chromosome pairs to ensure their
      proper meiotic segregation. Competing hypotheses seek to explain the emerging
      findings of significant heterogeneity in recombination rates within and between
      genomes, but intraspecific comparisons of genome-wide recombination patterns are
      rare. The honey bee (Apis mellifera) exhibits the highest rate of genomic
      recombination among multicellular animals with about five cross-over events per
      chromatid. RESULTS: Here, we present a comparative analysis of recombination
      rates across eight genetic linkage maps of the honey bee genome to investigate
      which genomic sequence features are correlated with recombination rate and with
      its variation across the eight data sets, ranging in average marker spacing
      ranging from 1 Mbp to 120 kbp. Overall, we found that GC content explained best
      the variation in local recombination rate along chromosomes at the analyzed 100
      kbp scale. In contrast, variation among the different maps was correlated to the
      abundance of microsatellites and several specific tri- and tetra-nucleotides.
      CONCLUSIONS: The combined evidence from eight medium-scale recombination maps of
      the honey bee genome suggests that recombination rate variation in this highly
      recombining genome might be due to the DNA configuration instead of distinct
      sequence motifs. However, more fine-scale analyses are needed. The empirical
      basis of eight differing genetic maps allowed for robust conclusions about the
      correlates of the local recombination rates and enabled the study of the relation
      between DNA features and variability in local recombination rates, which is
      particularly relevant in the honey bee genome with its exceptionally high
      recombination rate.

PMID- 25765998
TI  - microRNAs with different functions and roles in disease development and as
      potential biomarkers of diabetes: progress and challenges.
AB  - Biomarkers provide information on early detection of diseases, in determining
      individuals at risk of developing complications or subtyping individuals for
      disease phenotypes. In addition, biomarkers may lead to better treatment
      strategies, personalized therapy, and improved outcome. A major gap in the field
      of biomarker development is that we have not identified appropriate (minimally
      invasive, life-style independent and informative) biomarkers for the underlying
      disease process(es) that can be measured in readily accessible samples (e.g.
      serum, plasma, blood, urine). miRNAs function as regulators in wide ranging
      cellular and physiological functions and also participate in many
      physiopathological processes and thus have been linked to many diseases including
      diabetes, metabolic and cardiovascular diseases, cancer, neurodegenerative
      diseases, and autoimmunity. Many miRNAs have been shown to have predictive value
      as potential biomarkers in a variety of diseases including diabetes, which are
      detectable in some instances many years before the manifestation of disease.
      Although some technical challenges still remain, due to their availability in the
      circulation, relative stability, and ease of detection; miRNAs have emerged as a
      promising new class of biomarkers to provide information on early detection of
      disease, monitoring disease progression, in determining individual's risk of
      developing complications or subtyping individuals for disease phenotypes, and to
      monitor response to therapeutic interventions. As a final note, most of the
      miRNAs reported in the literature have not yet been validated in sufficiently
      powered and longitudinal studies for specificity for that particular disease. 

PMID- 25766000
TI  - Red and processed meat consumption and purchasing behaviours and attitudes:
      impacts for human health, animal welfare and environmental sustainability.
AB  - OBJECTIVE: Higher intakes of red and processed meat are associated with poorer
      health outcomes and negative environmental impacts. Drawing upon a population
      survey the present paper investigates meat consumption behaviours, exploring
      perceived impacts for human health, animal welfare and the environment. DESIGN:
      Structured self-completion postal survey relating to red and processed meat,
      capturing data on attitudes, sustainable meat purchasing behaviour, red and
      processed meat intake, plus sociodemographic characteristics of respondents.
      SETTING: Urban and rural districts of Nottinghamshire, East Midlands, UK, drawn
      from the electoral register. SUBJECTS: UK adults (n 842) aged 18-91 years, 497
      females and 345 males, representing a 35.6 % response rate from 2500 randomly
      selected residents. RESULTS: Women were significantly more likely (P60 years)
      were more likely to hold positive attitudes towards animal welfare (P<0.01). Less
      than a fifth (18.4 %) of the sample agreed that the impact of climate change
      could be reduced by consuming less meat, dairy products and eggs. Positive
      attitudes towards animal welfare were associated with consuming less meat and a
      greater frequency of 'higher welfare' meat purchases. CONCLUSIONS: Human health
      and animal welfare are more common motivations to avoid red and processed meat
      than environmental sustainability. Policy makers, nutritionists and health
      professionals need to increase the public's awareness of the environmental impact
      of eating red and processed meat. A first step could be to ensure that dietary
      guidelines integrate the nutritional, animal welfare and environmental components
      of sustainable diets.

PMID- 25765999
TI  - Heterozygous deletion of FOXA2 segregates with disease in a family with
      heterotaxy, panhypopituitarism, and biliary atresia.
AB  - Biliary atresia (BA) is a pediatric cholangiopathy with unknown etiology
      occurring in isolated and syndromic forms. Laterality defects affecting the
      cardiovascular and gastrointestinal systems are the most common features present
      in syndromic BA. Most cases are sporadic, although reports of familial cases have
      led to the hypothesis of genetic susceptibility in some patients. We identified a
      child with BA, malrotation, and interrupted inferior vena cava whose father
      presented with situs inversus, polysplenia, panhypopituitarism, and mildly
      dysmorphic facial features. Chromosomal microarray analysis demonstrated a 277 kb
      heterozygous deletion on chromosome 20, which included a single gene, FOXA2, in
      the proband and her father. This deletion was confirmed to be de novo in the
      father. The proband and her father share a common diagnosis of heterotaxy, but
      they also each presented with a variety of other issues. Further genetic
      screening revealed that the proband carried an additional protein-altering
      polymorphism (rs1904589; p.His165Arg) in the NODAL gene that is not present in
      the father, and this variant has been shown to decrease expression of the gene.
      As FOXA2 can be a regulator of NODAL expression, we propose that
      haploinsufficiency for FOXA2 combined with a decreased expression of NODAL is the
      likely cause for syndromic BA in this proband.

PMID- 25766001
TI  - The cortical sensory representation of genitalia in women and men: a systematic
      review.
AB  - Background : Although genital sensations are an essential aspect of sexual
      behavior, the cortical somatosensory representation of genitalia in women and men
      remain poorly known and contradictory results have been reported. Objective : To
      conduct a systematic review of studies based on electrophysiological and
      functional neuroimaging studies, with the aim to identify insights brought by
      modern methods since the early descriptions of the sensory homunculus in the
      primary somatosensory cortex (SI). Results : The review supports the
      interpretation that there are two distinct representations of genital sensations
      in SI, one on the medial surface and the other on the lateral surface. In
      addition, the review suggests that the secondary somatosensory cortex and the
      posterior insula support a representation of the affective aspects of genital
      sensation. Conclusion : In view of the erogenous character of sensations
      originating in the genitalia, future studies on this topic should systematically
      assess qualitatively as well as quantitatively the sexually stimulating and/or
      sexually pleasurable characteristics of sensations felt by subjects in response
      to experimental stimuli. 

PMID- 25766002
TI  - Bloom syndrome radials are predominantly non-homologous and are suppressed by
      phosphorylated BLM.
AB  - Biallelic mutations in BLM cause Bloom syndrome (BS), a genome instability
      disorder characterized by growth retardation, sun sensitivity and a
      predisposition to cancer. As evidence of decreased genome stability, BS cells
      demonstrate not only elevated levels of spontaneous sister chromatid exchanges
      (SCEs), but also exhibit chromosomal radial formation. The molecular nature and
      mechanism of radial formation is not known, but radials have been thought to be
      DNA recombination intermediates between homologs that failed to resolve. However,
      we find that radials in BS cells occur over 95% between non-homologous
      chromosomes, and occur non-randomly throughout the genome. BLM must be
      phosphorylated at T99 and T122 for certain cell cycle checkpoints, but it is not
      known whether these modifications are necessary to suppress radial formation. We
      find that exogenous BLM constructs preventing phosphorylation at T99 and T122 are
      not able to suppress radial formation in BS cells, but are able to inhibit SCE
      formation. These findings indicate that BLM functions in 2 distinct pathways
      requiring different modifications. In one pathway, for which the phosphorylation
      marks appear dispensable, BLM functions to suppress SCE formation. In a second
      pathway, T99 and T122 phosphorylations are essential for suppression of
      chromosomal radial formation, both those formed spontaneously and those formed
      following interstrand crosslink damage.

PMID- 25766003
TI  - [Fournier's gangrene: Cervical and facial extension. A very rare case].
AB  - Fournier's gangrene is a fearsome disease with a bad prognosis and a mortality
      rate ranging between 10 and 80% according to the literature. It is extensive in
      13 to 54% of cases. Up to date, cervico-facial extension has never been reported.
      We describe the case of a 51-year-old overweighed woman with a history of type 2
      diabetes and a narrow lumbar canal who was referred to our institution for
      significant fatigue and increasingly painful legs. A diagnosis of Fournier's
      gangrene was made after correlating the physical findings with the results of a
      full body scan. Diffuse subcutaneous emphysema involving the face, neck,
      mediastinum, abdominal wall, right buttock, perineum and the right thigh was
      identified. Treatment included multiple surgical debridements, admission to
      intensive care unit, and an efficient antibiotic therapy that enabled
      preservation of the patient's life. To our knowledge, this is the first case of
      cervical and mediastinal extension of Fournier's gangrene to be reported. No
      clear guidelines exit on the management of this complication (cervico-facial and
      mediastinal drainage). We share our experience of this unusual case.

PMID- 25766004
TI  - Could beta-hemolytic, group B Enterococcus faecalis be mistaken for Streptococcus
      agalactiae?
AB  - A beta-hemolytic Enterococcus faecalis strain agglutinating Lancefield group A,
      B, C, D, F, and G antisera was observed from a rectovaginal swab, in the context
      of antenatal screening for Streptococcus agalactiae (group B Streptococcus
      [GBS]). This is the first multi-Lancefield antisera-agglutinating isolate of this
      species, and it raised particular concern, as it may mimic GBS, leading to false
      reporting and useless receipt of intrapartum antibiotics. 

PMID- 25766006
TI  - Effects of storage and thawing conditions on coagulation testing.
AB  - INTRODUCTION: Current recommendations for coagulation testing storage and thawing
      are based on historical studies that were performed using unbuffered 3.8% sodium
      citrate. We sought to measure the effects of freezing and thawing conditions 3.2%
      buffered sodium citrate plasma samples that have been stored in vials with either
      snap or sealed screw tops, frozen in -70  degrees C freezer or dry ice and thawed
      either capped or uncapped. METHODS: Shed blood samples were pooled and then
      aliquoted into four snap top and four screw tops vials. Half the vials were
      stored in a -70  degrees C freezer, and half on dry ice for at least 16 h.
      Afterwards, half the frozen samples were thawed in 37  degrees C waterbath
      capped, and other half were thawed capped. After thawing cycles, samples were
      tested for PT, activated partial thromboplastin time (APTT), fibrinogen, D-dimer,
      factor assays, von Willebrand factor activity, plasminogen, antithrombin, protein
      C and lupus anticoagulant. RESULTS: Prothrombin time, APTT, factor X, and lupus
      anticoagulant testing were affected by all vials, freezing and thawing
      conditions, whereas fibrinogen, D-dimer, von Willebrand activity or protein C
      were not affected by any vial, freezing or storage condition. CONCLUSIONS:
      Storage vials, freezing and thawing condition affect coagulation testing,
      although these differences may not be clinically significant.

PMID- 25766005
TI  - Intestinal carriage of Shewanella xiamenensis simulating carriage of OXA-48
      producing Enterobacteriaceae.
AB  - Positivity for bla(OXA-48)-like carbapenemase genes was revealed by molecular
      testing of a surveillance rectal swab from a patient who had previously been
      colonized and infected by an OXA-48-producing Klebsiella pneumoniae. Positivity
      was due to a coincidental carriage of Shewanella xiamenensis harboring a new
      bla(OXA-48)-like gene, while the K. pneumoniae was no longer present.

PMID- 25766007
TI  - A settling curve modeling method for quantitative description of the dispersion
      stability of carbon nanotubes in aquatic environments.
AB  - Understanding the aggregation and deposition behavior of carbon nanotubes (CNTs)
      is of great significance in terms of their fate and transport in the environment.
      Attachment efficiency is a widely used index for well-dispersed CNT solutions.
      However, in natural waters, CNTs are usually heterogeneous in particle size. The
      attachment efficiency method is not applicable to such systems. Describing the
      dispersion stability of CNTs in natural aquatic systems is still a challenge. In
      this work, a settling curve modeling (SCM) method was developed for the
      description of the aggregation and deposition behavior of CNTs in aqueous
      solutions. The effects of water chemistry (natural organic matter, pH, and ionic
      strength) on the aggregation and deposition behavior of pristine and surface
      functionalized multi-walled carbon nanotubes (MWCNTs) were systematically studied
      to evaluate the reliability of the SCM method. The results showed that, as
      compared to particle size and optical density, the centrifugal sedimentation rate
      constant (ks) from the settling curve profile is a practical, useful and reliable
      index for the description of heterogeneous CNT suspensions. The SCM method was
      successfully applied to MWCNT in three natural waters. The constituents in water,
      especially organic matter, determine the dispersion stability of MWCNTs in
      natural water bodies. 

PMID- 25766008
TI  - Antimony leaching release from brake pads: Effect of pH, temperature and organic
      acids.
AB  - Metals from automotive brake pads pollute water, soils and the ambient air. The
      environmental effect on water of antimony (Sb) contained in brake pads has been
      largely untested. The content of Sb in one abandoned brake pad reached up to
      1.62*10(4) mg/kg. Effects of initial pH, temperature and four organic acids
      (acetic acid, oxalic acid, citric acid and humic acid) on Sb release from brake
      pads were studied using batch reactors. Approximately 30% (97 mg/L) of the total
      Sb contained in the brake pads was released in alkaline aqueous solution and at
      higher temperature after 30 days of leaching. The organic acids tested restrained
      Sb release, especially acetic acid and oxalic acid. The pH-dependent
      concentration change of Sb in aqueous solution was best fitted by a logarithmic
      function. In addition, Sb contained in topsoil from land where brake pads were
      discarded (average 9*10(3) mg/kg) was 3000 times that in uncontaminated soils
      (2.7+/-1 mg/kg) in the same areas. Because potentially high amounts of Sb may be
      released from brake pads, it is important that producers and environmental
      authorities take precautions.

PMID- 25766009
TI  - Molecular diversity of arbuscular mycorrhizal fungi at a large-scale antimony
      mining area in southern China.
AB  - Arbuscular mycorrhizal fungi (AMF) have great potential for assisting heavy metal
      hyperaccumulators in the remediation of contaminated soils. However, little
      information is available about the community composition of AMF under natural
      conditions in soils contaminated by antimony (Sb). The objective of this study
      was to investigate the characteristics of AMF molecular diversity, and to explore
      the effects of Sb content and soil properties on the AMF community structure in
      an Sb mining area. Four Sb mine spoils and one adjacent reference area were
      selected from around the Xikuangshan mine in southern China. The association of
      AMF molecular diversity and community composition with the rhizosphere soils of
      the dominant plant species was studied by Polymerase Chain Reaction-Denaturing
      Gradient Gel Electrophoresis (PCR-DGGE). Results from all five studied sites
      showed that the diversity of AMF decreased with increasing Sb concentration.
      Principal component analysis (PCA) indicated that the AMF community structure was
      markedly different among these groups. Further redundancy analysis (RDA) showed
      that Sb contamination was the dominating factor influencing the AMF community
      structure in the Sb mine area. However, the multivariate analysis showed that,
      apart from the soil Sb content, extractable nitrogen content and organic matter
      content also attributed to AMF sequence distribution type. Some AMF sequences
      were only found in the highly contaminated area and these might be ideal
      candidates for improving phytoremediation efficiency in Sb mining regions. Gene
      sequencing analysis revealed that most species were affiliated with Glomus,
      suggesting that Glomus was the dominant AMF genus in the studied Sb mining area. 

PMID- 25766010
TI  - Elevated CO2 facilitates C and N accumulation in a rice paddy ecosystem.
AB  - Elevated CO2 can stimulate wetland carbon (C) and nitrogen (N) exports through
      gaseous and dissolved pathways, however, the consequent influences on the C and N
      pools are still not fully known. Therefore, we set up a free-air CO2 enrichment
      experiment in a paddy field in Eastern China. After five year fumigation, we
      studied C and N in the plant-water-soil system. The results showed: (1) elevated
      CO2 stimulated rice aboveground biomass and N accumulations by 19.1% and 12.5%,
      respectively. (2) Elevated CO2 significantly increased paddy soil TOC and TN
      contents by 12.5% and 15.5%, respectively in the 0-15 cm layer, and 22.7% and
      26.0% in the 15-30 cm soil layer. (3) Averaged across the rice growing period,
      elevated CO2 greatly increased TOC and TN contents in the surface water by 7.6%
      and 11.4%, respectively. (4) The TOC/TN ratio and natural delta15N value in the
      surface soil showed a decreasing trend under elevated CO2. The above results
      indicate that elevated CO2 can benefit C and N accumulation in paddy fields.
      Given the similarity between the paddies and natural wetlands, our results also
      suggest a great potential for long-term C and N accumulation in natural wetlands
      under future climate patterns.

PMID- 25766011
TI  - Characterization of odorous charge and photochemical reactivity of VOC emissions
      from a full-scale food waste treatment plant in China.
AB  - Food waste treatment plants (FWTPs) are usually associated with odorous nuisance
      and health risks, which are partially caused by volatile organic compound (VOC)
      emissions. This study investigated the VOC emissions from a selected full-scale
      FWTP in China. The feedstock used in this plant was mainly collected from local
      restaurants. For a year, the FWTP was closely monitored on specific days in each
      season. Four major indoor treatment units of the plant, including the storage
      room, sorting/crushing room, hydrothermal hydrolysis unit, and aerobic
      fermentation unit, were chosen as the monitoring locations. The highest mean
      concentration of total VOC emissions was observed in the aerobic fermentation
      unit at 21,748.2-31,283.3 MUg/m3, followed by the hydrothermal hydrolysis unit at
      10,798.1-23,144.4 MUg/m3. The detected VOC families included biogenic compounds
      (oxygenated compounds, hydrocarbons, terpenes, and organosulfur compounds) and
      abiogenic compounds (aromatic hydrocarbons and halocarbons). Oxygenated
      compounds, particularly alcohols, were the most abundant compounds in all
      samples. With the use of odor index analysis and principal components analysis,
      the hydrothermal hydrolysis and aerobic fermentation units were clearly
      distinguished from the pre-treatment units, as characterized by their higher
      contributions to odorous nuisance. Methanthiol was the dominant odorant in the
      hydrothermal hydrolysis unit, whereas aldehyde was the dominant odorant in the
      aerobic fermentation unit. Terpenes, specifically limonene, had the highest level
      of propylene equivalent concentration during the monitoring periods. This
      concentration can contribute to the increase in the atmospheric reactivity and
      ozone formation potential in the surrounding air.

PMID- 25766012
TI  - Comparison between UV and VUV photolysis for the pre- and post-treatment of
      coking wastewater.
AB  - In this study, ultraviolet (UV) and vacuum ultraviolet (VUV) photolysis were
      investigated for the pre-treatment and post-treatment of coking wastewater.
      First, 6-fold diluted raw coking wastewater was irradiated by UV and VUV. It was
      found that 15.9%-35.4% total organic carbon (TOC) was removed after 24 hr
      irradiation. The irradiated effluent could be degraded by the acclimated
      activated sludge. Even though the VUV photolysis removed more chemical oxygen
      demand (COD) than UV, the UV-irradiated effluent demonstrated better
      biodegradability. After 4 hr UV irradiation, the biological oxygen demand
      BOD5/COD ratio of irradiated coking wastewater increased from 0.163 to 0.224, and
      its toxicity decreased to the greatest extent. Second, the biologically treated
      coking wastewater was irradiated by UV and VUV. Both of them were able to remove
      37%-47% TOC within 8 hr irradiation. Compared to UV, VUV photolysis could
      significantly improve the transparency of the bio-treated effluent. VUV also
      reduced 7% more ammonia nitrogen (NH4+-N), 17% more nitrite nitrogen (NO2--N),
      and 18% more total nitrogen (TN) than UV, producing 35% less nitrite nitrogen
      (NO3--N) as a result. In conclusion, UV irradiation was better in improving the
      biodegradability of coking wastewater, while VUV was more effective at
      photolyzing the residual organic compounds and inorganic N-species in the bio
      treated effluent.

PMID- 25766013
TI  - Synthesis, crystal structure, photodegradation kinetics and photocatalytic
      activity of novel photocatalyst ZnBiYO4.
AB  - ZnBiYO4 was synthesized by a solid-state reaction method for the first time. The
      structural and photocatalytic properties of ZnBiYO4 were characterized by X-ray
      diffraction, scanning electron microscopy, X-ray photoelectron spectroscopy and
      UV-Vis diffuse reflectance. ZnBiYO4 crystallized with a tetragonal spinel
      structure with space group I41/A. The lattice parameters for ZnBiYO4 were
      a=b=11.176479A and c=10.014323A. The band gap of ZnBiYO4 was estimated to be
      1.58eV. The photocatalytic activity of ZnBiYO4 was assessed by photodegradation
      of methyl orange under visible light irradiation. The results showed that ZnBiYO4
      had higher catalytic activity compared with N-doped TiO2 under the same
      experimental conditions using visible light irradiation. The photocatalytic
      degradation of methyl orange with ZnBiYO4 or N-doped TiO2 as catalyst followed
      first-order reaction kinetics, and the first-order rate constant was 0.01575 and
      0.00416 min(-1) for ZnBiYO4 and N-doped TiO2, respectively. After visible light
      irradiation for 220 min with ZnBiYO4 as catalyst, complete removal and
      mineralization of methyl orange were observed. The reduction of total organic
      carbon, formation of inorganic products, SO4(2-) and NO3-, and evolution of CO2
      revealed the continuous mineralization of methyl orange during the photocatalytic
      process. The intermediate products were identified using liquid chromatography
      mass spectrometry. The ZnBiYO4/(visible light) photocatalysis system was found to
      be suitable for textile industry wastewater treatment and could be used to solve
      other environmental chemical pollution problems.

PMID- 25766014
TI  - Sources and characteristics of fine particles over the Yellow Sea and Bohai Sea
      using online single particle aerosol mass spectrometer.
AB  - Marine aerosols over the East China Seas are heavily polluted by continental
      sources. During the Chinese Comprehensive Ocean Experiment in November 2012, size
      and mass spectra of individual atmospheric particles in the size range from 0.2
      to 2.0 MUm were measured on board by a single particle aerosol mass spectrometer
      (SPAMS). The average hourly particle number (PN) was around 4560+/-3240 in the
      South Yellow Sea (SYS), 2900+/-3970 in the North Yellow Sea (NYS), and 1700+/
      2220 in the Bohai Sea (BS). PN in NYS and BS varied greatly over 3 orders of
      magnitude, while that in SYS varied slightly. The size distributions were fitted
      with two log-normal modes. Accumulation mode dominated in NYS and BS, especially
      during episodic periods. Coarse mode particles played an important role in SYS.
      Particles were classified using an adaptive resonance theory based neural network
      algorithm (ART-2a). Six particle types were identified with secondary-containing,
      aged sea-salt, soot-like, biomass burning, fresh sea-salt, and lead-containing
      particles accounting for 32%, 21%, 18%, 16%, 4%, and 3% of total PN,
      respectively. Aerosols in BS were relatively enriched in particles from
      anthropogenic sources compared to SYS, probably due to emissions from more
      developed upwind regions and indicating stronger influence of continental outflow
      on marine environment. Variation of source types depended mainly on origins of
      transported air masses. This study examined rapid changes in PN, size
      distribution and source types of fine particles in marine atmospheres. It also
      demonstrated the effectiveness of high-time-resolution source apportionment by
      ART-2a.

PMID- 25766015
TI  - Flower-, wire-, and sheet-like MnO2-deposited diatomites: Highly efficient
      absorbents for the removal of Cr(VI).
AB  - Flower-, wire-, and sheet-like MnO2-deposited diatomites have been prepared using
      a hydrothermal method with Mn(Ac)2, KMnO4 and/or MnSO4 as Mn source and diatomite
      as support. Physical properties of the materials were characterized by means of
      numerous analytical techniques, and their behaviors in the adsorption of
      chromium(VI) were evaluated. It is shown that the MnO2-deposited diatomite
      samples with different morphologies possessed high surface areas and abundant
      surface hydroxyl groups (especially the wire-like MnO2/diatomite sample). The
      wire-like MnO2/diatomite sample showed the best performance in the removal of
      Cr(VI), giving the maximum Cr(VI) adsorption capacity of 101 mg/g.

PMID- 25766016
TI  - Methane and nitrous oxide emissions from a subtropical coastal embayment (Moreton
      Bay, Australia).
AB  - Surface water methane (CH4) and nitrous oxide (N2O) concentrations and fluxes
      were investigated in two subtropical coastal embayments (Bramble Bay and
      Deception Bay, which are part of the greater Moreton Bay, Australia).
      Measurements were done at 23 stations in seven campaigns covering different
      seasons during 2010-2012. Water-air fluxes were estimated using the Thin Boundary
      Layer approach with a combination of wind and currents-based models for the
      estimation of the gas transfer velocities. The two bays were strong sources of
      both CH4 and N2O with no significant differences in the degree of saturation of
      both gases between them during all measurement campaigns. Both CH4 and N2O
      concentrations had strong temporal but minimal spatial variability in both bays.
      During the seven seasons, CH4 varied between 500% and 4000% saturation while N2O
      varied between 128 and 255% in the two bays. Average seasonal CH4 fluxes for the
      two bays varied between 0.5+/-0.2 and 6.0+/-1.5 mg CH4/(m2.day) while N2O varied
      between 0.4+/-0.1 and 1.6+/-0.6 mg N2O/(m2.day). Weighted emissions (t CO2-e)
      were 63%-90% N2O dominated implying that a reduction in N2O inputs and/or
      nitrogen availability in the bays may significantly reduce the bays' greenhouse
      gas (GHG) budget. Emissions data for tropical and subtropical systems is still
      scarce. This work found subtropical bays to be significant aquatic sources of
      both CH4 and N2O and puts the estimated fluxes into the global context with
      measurements done from other climatic regions.

PMID- 25766017
TI  - Insights on the solubilization products after combined alkaline and ultrasonic
      pre-treatment of sewage sludge.
AB  - This work provides insights on the solubilization products after a simultaneous
      combination of alkaline and ultrasonic (ALK+ULS) pre-treatment of sewage sludge.
      Soluble chemical oxygen demand (SCOD) increased from 1200 to 11,000 mg/L after
      such treatment. Organics with molecular weight around 5.6 kDa were solubilized
      because of the synergistic effect of ultrasound and alkali. Organics with
      molecular weight larger than 300 kDa increased from 7.8% to 60%, 16% and 42.3%
      after ULS, ALK and ALK+ULS treatment, respectively. Excitation emission matrix
      fluorescence spectroscopy analysis identified soluble microbial product-like and
      humic acid-like matters as the main solubilization products. Sludge anaerobic
      biodegradability was significantly enhanced with the simultaneous application of
      ALK+ULS pre-treatment. ALK+ULS pre-treatment resulted in 37.8% biodegradability
      increase compared to the untreated sludge. This value was higher compared to the
      biodegradability increase induced by individual ALK pre-treatment (5.7%) or
      individual ULS pre-treatment (20.7%) under the same conditions applied.

PMID- 25766018
TI  - Phosphorus recovery from biogas fermentation liquid by Ca-Mg loaded biochar.
AB  - Shortage in phosphorus (P) resources and P wastewater pollution is considered as
      a serious problem worldwide. The application of modified biochar for P recovery
      from wastewater and reuse of recovered P as agricultural fertilizer is a
      preferred process. This work aims to develop a calcium and magnesium loaded
      biochar (Ca-Mg/biochar) application for P recovery from biogas fermentation
      liquid. The physico-chemical characterization, adsorption efficiency, adsorption
      selectivity, and postsorption availability of Ca-Mg/biochar were investigated.
      The synthesized Ca-Mg/biochar was rich in organic functional groups and in CaO
      and MgO nanoparticles. With the increase in synthesis temperature, the yield
      decreased, C content increased, H content decreased, N content remained the same
      basically, and BET surface area increased. The P adsorption of Ca-Mg/biochar
      could be accelerated by nano-CaO and nano-MgO particles and reached equilibrium
      after 360min. The process was endothermic, spontaneous, and showed an increase in
      the disorder of the solid-liquid interface. Moreover, it could be fitted by the
      Freundlich model. The maximum P adsorption amounts were 294.22, 315.33, and
      326.63mg/g. The P adsorption selectivity of Ca-Mg/biochar could not be
      significantly influenced by the typical pH level of biogas fermentation liquid.
      The nano-CaO and nano-MgO particles of Ca-Mg/biochar could reduce the negative
      interaction effects of coexisting ions. The P releasing amounts of postsorption
      Ca-Mg/biochar were in the order of Ca-Mg/B600>Ca-Mg/B450>Ca-Mg/B300. Results
      revealed that postsorption Ca-Mg/biochar can continually release P and is more
      suitable for an acid environment.

PMID- 25766019
TI  - Characterization of the archaeal community fouling a membrane bioreactor.
AB  - Biofilm formation, one of the primary causes of biofouling, results in reduced
      membrane flux or increased transmembrane pressure and thus represents a major
      impediment to the wider implementation of membrane bioreactor (MBR) technologies
      for water purification. Most studies have focused on the role of bacteria in
      membrane fouling as they are the most dominant and best studied organisms present
      in the MBR. In contrast, there is limited information on the role of the archaeal
      community in biofilm formation in MBRs. This study investigated the composition
      of the archaeal community during the process of biofouling in an MBR. The
      archaeal community was observed to have lower richness and diversity in the
      biofilm than the sludge during the establishment of biofilms at low transmembrane
      pressure (TMP). Clustering of the communities based on the Bray-Curtis similarity
      matrix indicated that a subset of the sludge archaeal community formed the
      initial biofilms. The archaeal community in the biofilm was mainly composed of
      Thermoprotei, Thermoplasmata, Thermococci, Methanopyri, Methanomicrobia and
      Halobacteria. Among them, the Thermoprotei and Thermoplasmata were present at
      higher relative proportions in the biofilms than they were in the sludge.
      Additionally, the Thermoprotei, Thermoplasmata and Thermococci were the dominant
      organisms detected in the initial biofilms at low TMP, while as the TMP
      increased, the Methanopyri, Methanomicrobia, Aciduliprofundum and Halobacteria
      were present at higher abundances in the biofilms at high TMP. 

PMID- 25766020
TI  - Effect of six kinds of scale inhibitors on calcium carbonate precipitation in
      high salinity wastewater at high temperatures.
AB  - Precipitation of calcium carbonate (CaCO3) scale on heat transfer surfaces is a
      serious and expensive problem widely occurring in numerous industrial processes.
      In this study, we compared the scale inhibition effect of six kinds of commercial
      scale inhibitors and screened out the best one (scale inhibitor SQ-1211) to
      investigate its scale inhibition performance in highly saline conditions at high
      temperature through static scale inhibition tests. The influences of scale
      inhibitor dosage, temperature, heating time and pH on the inhibition efficiency
      of the optimal scale inhibitor were investigated. The morphologies and crystal
      structures of the precipitates were characterized by Scanning Electron Microscopy
      and X-ray Diffraction analysis. Results showed that the scale inhibition
      efficiency of the optimal scale inhibitor decreased with the increase of the
      reaction temperature. When the concentration of Ca2+ was 1600 mg/L, the scale
      inhibition rate could reach 90.7% at 80 degrees C at pH8. The optimal scale
      inhibitor could effectively retard scaling at high temperature. In the presence
      of the optimal scale inhibitor, the main crystal structure of CaCO3 changed from
      calcite to aragonite.

PMID- 25766021
TI  - Experimental and molecular dynamic simulation study of perfluorooctane sulfonate
      adsorption on soil and sediment components.
AB  - Soil and sediment play a crucial role in the fate and transport of
      perfluorooctane sulfonate (PFOS) in the environment. However, the molecular
      mechanisms of major soil/sediment components on PFOS adsorption remain unclear.
      This study experimentally isolated three major components in soil/sediment:
      humin/kerogen, humic/fulvic acid (HA/FA), and inorganic component after removing
      organics, and explored their contributions to PFOS adsorption using batch
      adsorption experiments and molecular dynamic simulations. The results suggest
      that the humin/kerogen component dominated the PFOS adsorption due to its
      aliphatic features where hydrophobic effect and phase transfer are the primary
      adsorption mechanism. Compared with the humin/kerogen, the HA/FA component
      contributed less to the PFOS adsorption because of its hydrophilic and polar
      characteristics. The electrostatic repulsion between the polar groups of HA/FA
      and PFOS anions was attributable to the reduced PFOS adsorption. When the soil
      organic matter was extracted, the inorganic component also plays a non-negligible
      role because PFOS molecules might form surface complexes on SiO2 surface. The
      findings obtained in this study illustrate the contribution of organic matters in
      soils and sediments to PFOS adsorption and provided new perspective to
      understanding the adsorption process of PFOS on micro-interface in the
      environment. 

PMID- 25766022
TI  - A fouling suppression system in submerged membrane bioreactors using
      dielectrophoretic forces.
AB  - A novel method was developed to suppress membrane fouling in submerged membrane
      bioreactors. The method is based on the dielectrophoretic (DEP) motion of
      particles in an inhomogeneous electrical field. Using a real sample of biomass as
      feed, the fouling-suppression performance using DEP with different electrical
      field intensities (60-160 V) and different frequencies (50-1000 Hz) was
      investigated. The fouling-suppression performance was found to relate closely
      with the intensity and frequency of the electrical field. A stronger electrical
      field was found to better recover the filtrate flux. This is because of a
      stronger DEP force acting on the biomass particles close to the membrane's
      surface. Above an intensity and frequency value of 130 V and 1 kHz, respectively
      the permeate flux was reduced due to an electrothermal effect.

PMID- 25766023
TI  - A 1-dodecanethiol-based phase transfer protocol for the highly efficient
      extraction of noble metal ions from aqueous phase.
AB  - A 1-dodecanethiol-based phase-transfer protocol is developed for the extraction
      of noble metal ions from aqueous solution to a hydrocarbon phase, which calls for
      first mixing the aqueous metal ion solution with an ethanolic solution of 1
      dodecanethiol, and then extracting the coordination compounds formed between
      noble metal ions and 1-dodecanethiol into a non-polar organic solvent. A number
      of characterization techniques, including inductively coupled plasma atomic
      emission spectroscopy, Fourier transform infrared spectroscopy, and
      thermogravimetric analysis demonstrate that this protocol could be applied to
      extract a wide variety of noble metal ions from water to dichloromethane with an
      efficiency of >96%, and has high selectivity for the separation of the noble
      metal ions from other transition metals. It is therefore an attractive
      alternative for the extraction of noble metals from water, soil, or waste printed
      circuit boards. 

PMID- 25766024
TI  - Intracellular biosynthesis of Au and Ag nanoparticles using ethanolic extract of
      Brassica oleracea L. and studies on their physicochemical and biological
      properties.
AB  - In this present study, we reported broccoli (Brassica oleracea L.) as a potential
      candidate for the synthesis of gold and silver nanoparticles (NPs) in green
      chemistry method. The synthesized metal nanoparticles are evaluated their
      antimicrobial efficacy against different human pathogenic organisms. The physico
      chemical properties of gold nanoparticles were analyzed using different
      analytical techniques such as a UV-Vis spectrophotometer, Field Emission Scanning
      Electron Microscopy, energy dispersive X-ray spectroscopy, X-ray diffraction and
      a Fourier Transform Infrared spectrophotometer. In addition, gold and silver NP
      antimicrobial efficacy was checked by disc diffusion assay. UV-Vis color
      intensity of the nanoparticles was shown at 540 and 450 nm for gold and silver
      nanoparticles respectively. Higher magnification of the Field Emission Scanning
      Electron Microscopy image shows the variable morphology of the gold nanoparticles
      such as spherical, rod and triangular shapes and silver nanoparticles were seen
      in spherical shapes. The average spherical size of the particles was observed in
      24-38 nm for gold and 30-45 nm for silver NPs. X-ray diffraction pattern
      confirmed the presence of gold nanoparticles and silver nanoparticles which were
      crystalline in nature. Additionally, the functional metabolites were identified
      by the Fourier Transform Infrared spectroscopy. IR spectra revealed phenols,
      alcohols, aldehydes (sugar moieties), vitamins and proteins are present in the
      broccoli extract which are accountable to synthesize the nanoparticles. The
      synthesized gold and silver NPs inhibited the growth of the tested bacterial and
      fungal pathogens at the concentration of 50 MUg/mL respectively. In addition,
      broccoli mediated gold and silver nanoparticles have shown potent antimicrobial
      activity against human pathogens.

PMID- 25766025
TI  - Forecasting of dissolved oxygen in the Guanting reservoir using an optimized NGBM
      (1,1) model.
AB  - An optimized nonlinear grey Bernoulli model was proposed by using a particle
      swarm optimization algorithm to solve the parameter optimization problem. In
      addition, each item in the first-order accumulated generating sequence was set in
      turn as an initial condition to determine which alternative would yield the
      highest forecasting accuracy. To test the forecasting performance, the optimized
      models with different initial conditions were then used to simulate dissolved
      oxygen concentrations in the Guanting reservoir inlet and outlet (China). The
      empirical results show that the optimized model can remarkably improve
      forecasting accuracy, and the particle swarm optimization technique is a good
      tool to solve parameter optimization problems. What's more, the optimized model
      with an initial condition that performs well in in-sample simulation may not do
      as well as in out-of-sample forecasting. 

PMID- 25766026
TI  - Individual particle analysis of aerosols collected at Lhasa City in the Tibetan
      Plateau.
AB  - To understand the composition and major sources of aerosol particles in Lhasa
      City on the Tibetan Plateau (TP), individual particles were collected from 2
      February to 8 March, 2013 in Tibet University. The mean concentrations of both
      PM2.5 and PM10 during the sampling were 25.7+/-21.7 and 57.2+/-46.7 MUg/m3,
      respectively, much lower than those of other cities in East and South Asia, but
      higher than those in the remote region in TP like Nam Co, indicating minor urban
      pollution. Combining the observations with the meteorological parameters and back
      trajectory analysis, it was concluded that local sources controlled the pollution
      during the sampling. Transmission electron microscopy (TEM) combined with energy
      dispersive X-ray spectra (EDS) was used to study 408 particles sampled on four
      days. Based on the EDS analysis, a total of 8 different particle categories were
      classified for all 408 particles, including Si-rich, Ca-rich, soot, K-rich, Fe
      rich, Pb-rich, Al-rich and other particles. The dominant elements were Si, Al and
      Ca, which were mainly attributed to mineral dust in the earth's crust such as
      feldspar and clay. Fe-, Pb-, K-, Al-rich particles and soot mainly originated
      from anthropogenic sources like firework combustion and biomass burning during
      the sampling. During the sampling, the pollution mainly came from mineral dust,
      while the celebration ceremony and religious ritual produced a large quantity of
      anthropogenic metal-bearing particles on 9 and 25 February 2013. Cement particles
      also had a minor influence. The data obtained in this study can be useful for
      developing pollution control strategies.

PMID- 25766027
TI  - Design and demonstration of a next-generation air quality attainment assessment
      system for PM2.5 and O3.
AB  - Due to the increasingly stringent standards, it is important to assess whether
      the proposed emission reduction will result in ambient concentrations that meet
      the standards. The Software for Model Attainment Test-Community Edition (SMAT-CE)
      is developed for demonstrating attainment of air quality standards of O3 and
      PM2.5. SMAT-CE improves computational efficiency and provides a number of
      advanced visualization and analytical functionalities on an integrated GIS
      platform. SMAT-CE incorporates historical measurements of air quality parameters
      and simulated air pollutant concentrations under a number of emission inventory
      scenarios to project the level of compliance to air quality standards in a
      targeted future year. An application case study of the software based on the U.S.
      National Ambient Air Quality Standards (NAAQS) shows that SMAT-CE is capable of
      demonstrating the air quality attainment of annual PM2.5 and 8-hour O3 for a
      proposed emission control policy. 

PMID- 25766028
TI  - Soil microbial response to waste potassium silicate drilling fluid.
AB  - Potassium silicate drilling fluids (PSDF) are a waste product of the oil and gas
      industry with potential for use in land reclamation. Few studies have examined
      the influence of PSDF on abundance and composition of soil bacteria and fungi.
      Soils from three representative locations for PSDF application in Alberta,
      Canada, with clay loam, loam and sand textures were studied with applications of
      unused, used once and used twice PSDF. For all three soils, applying >=40 m3/ha
      of used PSDF significantly affected the existing soil microbial flora. No
      microbiota was detected in unused PSDF without soil. Adding used PSDF to soil
      significantly increased total fungal and aerobic bacterial colony forming units
      in dilution plate counts, and anaerobic denitrifying bacteria numbers in serial
      growth experiments. Used PSDF altered bacterial and fungal colony forming unit
      ratios of all three soils.

PMID- 25766029
TI  - Enhanced catalytic complete oxidation of 1,2-dichloroethane over mesoporous
      transition metal-doped gamma-Al2O3.
AB  - High-surface-area mesoprous powders of gamma-Al2O3 doped with Cu2+, Cr3+, and V3+
      ions were prepared via a modified sol-gel method and were investigated as
      catalysts for the oxidation of chlorinated organic compounds. The composites
      retained high surface areas and pore volumes comparable with those of undoped
      gamma-Al2O3 and the presence of the transition metal ions enhanced their surface
      acidic properties. The catalytic activity of the prepared catalysts in the
      oxidation of 1,2-dichloroethane (DCE) was studied in the temperature range of 250
      400 degrees C. The catalytic activity and product selectivity were strongly
      dependent on the presence and the type of dopant ion. While Cu2+- and Cr3+
      containing catalysts showed 100% conversion at 300 degrees C and 350 degrees C,
      V3+-containing catalyst showed considerably lower conversion. Furthermore, while
      the major products of the reactions over gamma-alumina were vinyl chloride
      (C2H3Cl) and hydrogen chloride (HCl) at all temperatures, Cu- and Cr-doped
      catalysts showed significantly stronger capability for deep oxidation to CO2.

PMID- 25766030
TI  - Role of nitric oxide in the genotoxic response to chronic microcystin-LR exposure
      in human-hamster hybrid cells.
AB  - Microcystin-LR (MC-LR) is the most abundant and toxic microcystin congener and
      has been classified as a potential human carcinogen (Group 2B) by the
      International Agency for Research on Cancer. However, the mechanisms underlying
      the genotoxic effects of MC-LR during chronic exposure are still poorly
      understood. In the present study, human-hamster hybrid (AL) cells were exposed to
      MC-LR for varying lengths of time to investigate the role of nitrogen radicals in
      MC-LR-induced genotoxicity. The mutagenic potential at the CD59 locus was more
      than 2-fold higher (p<0.01) in AL cells exposed to a cytotoxic concentration (1
      MUmol/L) of MC-LR for 30 days than in untreated control cells, which was
      consistent with the formation of micronucleus. MC-LR caused a dose-dependent
      increase in nitric oxide (NO) production in treated cells. Moreover, this was
      blocked by concurrent treatment with the NO synthase inhibitor NG-methyl-L
      arginine (L-NMMA), which suppressed MC-LR-induced mutations as well. The survival
      of mitochondrial DNA-depleted (rho0) AL cells was markedly decreased by MC-LR
      treatment compared to that in AL cells, while the CD59 mutant fraction was
      unaltered. These results provided clear evidence that the genotoxicity associated
      with chronic MC-LR exposure in mammalian cells was mediated by NO and might be
      considered as a basis for the development of therapeutics that prevent
      carcinogenesis.

PMID- 25766031
TI  - Application of a method used to deconstruct a single dose pharmacokinetic profile
      from multiple dose data.
AB  - With traditional non-compartmental methods, it is challenging to deconstruct
      plasma concentration versus time curves to assess the influence of individual
      doses. This study describes the application of a mathematical approach used to
      deconstruct a single dose curve using data derived from the second, third, fourth
      or nth dosing interval. Using data from a prospective clinical trial it is
      demonstrated that this approach reliably estimates pharmacokinetic parameters
      measured following two doses of zolpidem tartrate. Additionally, the study
      demonstrates the application of this approach using previously published data
      from a single- and multiple-dose pharmacokinetic study of the antibiotic
      gatifloxacin. Copyright (c) 2015 John Wiley & Sons, Ltd.

PMID- 25766032
TI  - Rolling-circle amplification detection of thrombin using surface-enhanced Raman
      spectroscopy with core-shell nanoparticle probe.
AB  - An ultrasensitive surface-enhanced Raman spectroscopy (SERS) sensor based on
      rolling-circle amplification (RCA)-increased "hot-spot" was developed for the
      detection of thrombin. The sensor contains a SERS gold nanoparticle@Raman
      label@SiO2 core-shell nanoparticle probe in which the Raman reporter molecules
      are sandwiched between a gold nanoparticle core and a thin silica shell by a
      layer-by-layer method. Thrombin aptamer sequences were immobilized onto the
      magnetic beads (MBs) through hybridization with their complementary strand. In
      the presence of thrombin, the aptamer sequence was released; this allowed the
      remaining single-stranded DNA (ssDNA) to act as primer and initiate in situ RCA
      reaction to produce long ssDNAs. Then, a large number of SERS probes were
      attached on the long ssDNA templates, causing thousands of SERS probes to be
      involved in each biomolecular recognition event. This SERS method achieved the
      detection of thrombin in the range from 1.0*10(-12) to 1.0*10(-8)  M and a
      detection limit of 4.2*10(-13)  M, and showed good performance in real serum
      samples. 

PMID- 25766033
TI  - The relationship between skill deficits and disability-a transdiagnostic study.
AB  - OBJECTIVE: Transdiagnostic skills (e.g., emotion regulation, stress management)
      and related self-concepts (e.g., self-esteem) are associated with the
      pathogenesis and course of different mental disorders. Evidence suggests that
      skill deficits coincide with not only specific psychopathology but also
      psychological strain and disability. So far, studies examining the relevance of
      several skills for a patient's disability are lacking. The aim of the present
      study was the combined assessment of 7 skills and self-concept variables to
      simultaneously analyze their relevance for disability. METHOD: We interviewed
      inpatients (N = 183) both on admission and discharge to assess 7 specific skills,
      7 areas of daily living disability, and psychopathological distress. RESULTS:
      Results support a relationship between several skills and disability (especially
      stress management), even while controlling for psychopathology. The improvement
      of skills and related self-concepts during therapy contributed substantially to
      the improvement of disability ratings. CONCLUSION: This study highlights the
      transdiagnostic importance of skills as well as the improvement of skills and
      related self-concepts as major determinants of disability. Parts of these effects
      are robust, even while controlling for psychopathology.

PMID- 25766034
TI  - Fasting plasma glucose levels predict steroid-induced abnormal glucose metabolism
      in patients with non-diabetic chronic kidney disease: a prospective cohort study.
AB  - BACKGROUND/AIMS: Glucocorticoids-induced abnormal glucose metabolism (AGM) is a
      common medical problem in patients with non-diabetic chronic kidney disease
      (CKD). However, little information is available regarding the prediction of
      steroid-induced AGM in this patient population. METHODS: In this prospective
      cohort study, we consecutively enrolled 303 non-diabetic CKD patients with
      fasting plasma glucose (FPG) levels <5.6 mmol/l and normal oral glucose tolerance
      test (OGTT). OGTT was performed every 3 months during glucocorticoid treatment to
      identify new-onset AGM, and patients were followed for 12 months post steroid
      withdrawal. RESULTS: During 593 person-years, there were 107 incident cases of
      steroid-induced AGM (18/100 person-year), including 55 (51.4%) diabetes and 52
      (48.6%) pre-diabetes. In a multivariate model, each millimole increase per liter
      in FPG enhanced the risk of AGM by 4.6-fold (hazard ratio 4.58, 95% confidence
      interval, 2.67-7.83). After adjusting other risk factors, a progressively
      increased risk of AGM or DM was observed in patients with FPG levels >=4.8
      mmol/l, as compared with those whose levels were <=4.3 mmol/l (p for trend
      <0.001). Furthermore, a greater increase in FPG level (>=0.3 mmol/l) during the
      first 3 months of glucocorticoid treatment was associated with an increased risk
      for future diabetes. For predicting steroid-induced diabetes, the area under the
      receiver-operating characteristic curve was 0.90 for the combination of FPG and
      changes in FPG levels at month 3. CONCLUSION: Higher-normal FPG and a greater
      increase in FPG levels during glucocorticoid treatment may help to identify non
      diabetic CKD patients at increased risk of steroid-induced AGM or diabetes.

PMID- 25766035
TI  - Polyhedral microcrystals encapsulating bone morphogenetic protein 2 improve
      healing in the alveolar ridge.
AB  - Atelocollagen sponges incorporating polyhedra encapsulating bone morphogenetic
      protein 2 (BMP-2) were implanted into lateral bone defects in the mandible. Half
      of the bone defects on the left side were treated with atelocollagen sponges
      containing 1.8 * 10(7) BMP-2 polyhedra, and half were treated with sponges
      containing 3.6 * 10(6) BMP-2 polyhedra. As controls, we treated the right-side
      bone defects in each animal with an atelocollagen sponge containing 5 ug of
      recombinant human BMP-2 (rhBMP-2) or 1.8 * 10(7) empty polyhedral. After a
      healing period of six months, whole mandibles were removed for micro-computed
      tomography (CT) and histological analyses. Micro-CT images showed that more bone
      had formed at all experimental sites than at control sites. However, the density
      of the new bone was not significantly higher at sites with an atelocollagen
      sponge containing BMP-2 polyhedra than at sites with an atelocollagen sponge
      containing rhBMP-2 or empty polyhedra. Histological examination confirmed that
      the BMP-2 polyhedra almost entirely replaced the atelocollagen sponges and
      connected the original bone with the regenerated bone. These results show that
      the BMP-2 delivery system facilitates the regeneration of new bone in the
      mandibular alveolar bone ridge and has an advance in the technology of bone
      regeneration for implant site development.

PMID- 25766036
TI  - Three-dimensional polycaprolactone-hydroxyapatite scaffolds combined with bone
      marrow cells for cartilage tissue engineering.
AB  - The goal of this study was to investigate the chondrogenic potential of three
      dimensional polycaprolactone-hydroxyapatite (PCL-HA) scaffolds loaded with bone
      marrow cells in vitro and the effect of PCL-HA scaffolds on osteochondral repair
      in vivo. Here, bone marrow was added to the prepared PCL-HA scaffolds and
      cultured in chondrogenic medium for 10 weeks. Osteochondral defects were created
      in the trochlear groove of 29 knees in 17 New Zealand white rabbits, which were
      then divided into four groups that underwent: implantation of PCL-HA scaffolds
      (left knee, n = 17; Group 1), microfracture (right knee, n = 6; Group 2),
      autologous osteochondral transplantation (right knee, n = 6; Group 3), and no
      treatment (right knee, n = 5; Control). Extracellular matrix produced by bone
      marrow cells covered the surface and filled the pores of PCL-HA scaffolds after
      10 weeks in culture. Moreover, many cell-laden cartilage lacunae were observed,
      and cartilage matrix was concentrated in the PCL-HA scaffolds. After a 12-week
      repair period, Group 1 showed excellent vertical and lateral integration with
      host bone, but incomplete cartilage regeneration and matrix accumulation. An
      uneven surface of regenerated cartilage and reduced distribution of cartilage
      matrix were observed in Group 2. In addition, abnormal bone growth and unstable
      integration between repaired and host tissues were detected. For Group 3, the
      integration between transplanted and host cartilage was interrupted. Our findings
      indicate that the PCL-HA scaffolds loaded with bone marrow cells improved
      chondrogenesis in vitro and implantation of PCL-HA scaffolds for osteochondral
      repairenhanced integration with host bone. However, cartilage regeneration
      remained unsatisfactory. The addition of trophic factors or the use of
      precultured cell-PCL-HA constructs for accelerated osteochondral repair requires
      further investigation.

PMID- 25766037
TI  - Preparation and evaluation of biocompatible long-term radiopaque microspheres
      based on polyvinyl alcohol and lipiodol for embolization.
AB  - The aim of this work was to develop long-term radiopaque microspheres (LRMs) by
      entrapping lipiodol in biocompatible polyvinyl alcohol with multiple emulsions
      chemical crosslinking method. The high content of lipiodol (0.366 g/mL) was
      hardly released from LRMs in vitro and the radiopacity could maintain at least 3
      months after subcutaneous injection in mice without weakening. A series of tests
      was performed to evaluate the feasibility of LRMs for embolization. LRMs were
      proved to be smooth, spherical, and well dispersed with diameter range of 100
      1200 MUm. Young's modulus of LRMs was 55.39 +/- 9.10 kPa and LRMs could be easily
      delivered through catheter without aggregating or clogging. No toxicity of LRMs
      was found to mouse L929 fibroblasts cells and only moderate inflammatory in
      surrounding tissue of mice was found after subcutaneous injection of LRMs. After
      LRMs were embolized in renal artery of a rabbit, the distribution and radiopacity
      of LRMs in vivo were easily detectable by X-ray fluoroscopy and computed
      tomography (CT) imaging, respectively. More accurate distribution of LRMs in
      embolized kidney and vessels could be detected by high-revolution visualization
      of micro-CT ex vivo. In conclusion, the LRMs were proved to be biocompatible and
      provide long-term radiopacity with good physical and mechanical properties for
      embolization.

PMID- 25766038
TI  - Development of emulsification resistant heavier-than-water tamponades using high
      molecular weight silicone oil polymers.
AB  - PURPOSE: Developing new blends of heavier-than-water silicone oil tamponade
      agents containing high molecular weight polydimethylsiloxane polymer for use in
      vitreoretinal surgery. MATERIALS AND METHODS: The viscoelastic properties of
      heavier-than-water silicone oil blends (30.5% F6H8 + 69.5% polydimethylsiloxane)
      containing high molecular weight polymer additive at increasing concentrations
      were measured using a controlled-stress rheometer (TA Instruments Rheolyst AR
      1000 N). Emulsification of the blends was induced using a sonication device and a
      pluronic surfactant as a strong emulsifier. The percentage emulsion area was
      photographed and measured using ImageJ software. In a second in vitro
      emulsification assessment, silicone oil blends were dispersed using a high shear
      homogenizer and the oil-in-water droplets were counted using a coulter counter
      particle analyser. RESULTS: The addition of the high molecular weight polymer
      increased shear viscosity and viscoelasticity of the oil blends, which were
      measureable and to some extent predictable. The in vitro emulsification models
      produced contradictory results. This demonstrates the difficulty of designing and
      using in vitro models to evaluate the emulsification tendency of tamponade agents
      in vivo. CONCLUSION: Addition of a high molecular weight polymer to heavy
      silicone oil can increase the viscoelasticity. These findings might contribute to
      the development of emulsification resistant heavy silicone oils.

PMID- 25766039
TI  - REDHORSE-REcombination and Double crossover detection in Haploid Organisms using
      next-geneRation SEquencing data.
AB  - BACKGROUND: Next-generation sequencing technology provides a means to study
      genetic exchange at a higher resolution than was possible using earlier
      technologies. However, this improvement presents challenges as the alignments of
      next generation sequence data to a reference genome cannot be directly used as
      input to existing detection algorithms, which instead typically use multiple
      sequence alignments as input. We therefore designed a software suite called
      REDHORSE that uses genomic alignments, extracts genetic markers, and generates
      multiple sequence alignments that can be used as input to existing recombination
      detection algorithms. In addition, REDHORSE implements a custom recombination
      detection algorithm that makes use of sequence information and genomic positions
      to accurately detect crossovers. REDHORSE is a portable and platform independent
      suite that provides efficient analysis of genetic crosses based on Next
      generation sequencing data. RESULTS: We demonstrated the utility of REDHORSE
      using simulated data and real Next-generation sequencing data. The simulated
      dataset mimicked recombination between two known haploid parental strains and
      allowed comparison of detected break points against known true break points to
      assess performance of recombination detection algorithms. A newly generated NGS
      dataset from a genetic cross of Toxoplasma gondii allowed us to demonstrate our
      pipeline. REDHORSE successfully extracted the relevant genetic markers and was
      able to transform the read alignments from NGS to the genome to generate multiple
      sequence alignments. Recombination detection algorithm in REDHORSE was able to
      detect conventional crossovers and double crossovers typically associated with
      gene conversions whilst filtering out artifacts that might have been introduced
      during sequencing or alignment. REDHORSE outperformed other commonly used
      recombination detection algorithms in finding conventional crossovers. In
      addition, REDHORSE was the only algorithm that was able to detect double
      crossovers. CONCLUSION: REDHORSE is an efficient analytical pipeline that serves
      as a bridge between genomic alignments and existing recombination detection
      algorithms. Moreover, REDHORSE is equipped with a recombination detection
      algorithm specifically designed for Next-generation sequencing data. REDHORSE is
      portable, platform independent Java based utility that provides efficient
      analysis of genetic crosses based on Next-generation sequencing data. REDHORSE is
      available at http://redhorse.sourceforge.net/ .

PMID- 25766040
TI  - Quantifying the Robustness of the English Sibilant Fricative Contrast in
      Children.
AB  - PURPOSE: Four measures of children's developing robustness of phonological
      contrast were compared to see how they correlated with age, vocabulary size, and
      adult listeners' correctness ratings. METHOD: Word-initial sibilant fricative
      productions from eighty-one 2- to 5-year-old children and 20 adults were
      phonetically transcribed and acoustically analyzed. Four measures of robustness
      of contrast were calculated for each speaker on the basis of the centroid
      frequency measured from each fricative token. Productions that were transcribed
      as correct from different children were then used as stimuli in a perception
      experiment in which adult listeners rated the goodness of each production.
      RESULTS: Results showed that the degree of category overlap, quantified as the
      percentage of a child's productions whose category could be correctly predicted
      from the output of a mixed-effects logistic regression model, was the measure
      that correlated best with listeners' goodness judgments. CONCLUSIONS: Even when
      children's productions have been transcribed as correct, adult listeners are
      sensitive to within-category variation quantified by the child's degree of
      category overlap. Further research is needed to explore the relationship between
      the age of a child and adults' sensitivity to different types of within-category
      variation in children's speech.

PMID- 25766041
TI  - Adherence to evidence-based secondary prevention pharmacotherapy in patients
      after an acute coronary syndrome: A systematic review.
AB  - OBJECTIVE: To synthesize current evidence on medication adherence rates and
      associated risk factors in patients after an acute coronary syndrome (ACS).
      METHODS: A systematic review was conducted. Five electronic databases and article
      bibliographies were searched for publications from 1990 to 2013 which assessed
      adherence to secondary prevention pharmacotherapy in adults after hospital
      discharge for an ACS. Identified studies were screened using pre-defined criteria
      for eligibility. A standardized form was used for data abstraction.
      Methodological quality was assessed using modified criteria for quantitative
      studies. RESULTS: Sixteen studies met our inclusion criteria. Post-discharge
      medication adherence rates at 1-year ranged between 54% and 86%. There were no
      consistent predictors of non-adherence across all cardiac medication classes
      examined. CONCLUSIONS: Adherence to secondary prevention pharmacotherapy was
      suboptimal in patients after hospital discharge for an ACS. Risk factors
      associated with non-adherence were examined in a limited number of studies, and
      the associations varied between these investigations.

PMID- 25766042
TI  - Family presence in the congenital catheterization laboratory.
AB  - Evidence suggests that family presence as an option during invasive procedures
      may provide a comforting presence to the patient and may not be notable
      disruptive to the health care team. Little research has explored family presence
      during cardiac procedures. This is the first documented report of family presence
      in the congenital cardiac catheterization lab (CCCL). The purpose of this article
      is to review the course for implementing a family presence program in the CCCL.
      The Iowa Model of Evidence-Based practice guided this process which included the
      development of a written policy of family presence in the CCCL at two academic
      medical centers. Successful family presence in the catheterization lab must
      include: written guidelines, involvement of all staff, family presence offered as
      an option, and preparation of the patient and family for the catheterization
      experience as well as emergency procedures. 

PMID- 25766043
TI  - A sanguineous pleuro pericardial effusion in a patient recently treated with
      Dabigatran.
AB  - Dabigatran, a direct thrombin inhibitor, is one of the new oral anticoagulants.
      As more patients receive treatment with Dabigatran, and as the clinical
      indications for Dabigatran use expand, reporting serious adverse effects is
      fundamental to future safety assessment. Although patients taking Dabigatran had
      fewer life-threatening bleeds when compared to Coumadin, those events continue to
      be reported. We describe, in the same patient, a sanguineous pleuro pericardial
      effusion that was diagnosed incidentally on a pre-ablation cardiac CT
      angiography. The diagnosis was made approximately two months after initiating
      Dabigatran treatment for non-valvular atrial fibrillation in a 63-year-old
      patient. 

PMID- 25766044
TI  - Jeopardizing Christmas: Why spoiled kids and a tight schedule could make Santa
      Claus fall?
AB  - Santa Claus' spatio-temporal gait characteristics, ground reaction forces during
      treadmill walking as well as postural sway during loaded, unloaded and cognitive
      interference tasks were examined in order to estimate his fall risk. Seventeen
      healthy males, disguised as researchers and students (age: 30+/-10 years; height:
      179+/-6 years; weight: 76+/-7kg; BMI: 24+/-2kg/m(2); physical activity: 12+/
      4h/week) and who still believe in Santa Claus randomly underwent balance and gait
      analyses with and without cognitive interference. The conditions were to be
      dressed as "Santa Claus" (wearing costume consisting of a beard, cap, robe, heavy
      sack with a load of 20kg) or dressed in "normal clothing" (no costume).
      Spatiotemporal gait parameters (walking velocity, gait variability and stride
      time, length and width), ground reaction forces (GRF) (left- and right-sided heel
      strike and push off) and postural sway (30s tandem stance on a force plate) were
      measured. "Santa-effects" (0.001<p<0.05; 0.21<etap(2)<0.72) and "Dual-task
      effects" (0.001<p<0.003; 0.46<etap(2)<0.86) were found for postural sway
      (increased sway), GRF (decreased forces for dual tasking, increased forces for
      the Santa condition) and the majority of spatio-temporal gait parameters.
      Significant "Santa"*"Dual-Task" interaction effects were not observed
      (0.001<p<0.05; 0.21<etap(2)<0.72). Relevant leg effects of GRF during walking
      were not found. Santa Claus faces a tremendously increased risk of falling when
      carrying his Christmas sack with 20kg of presents. Cognitive loads also impair
      his neuromuscular performance. It is recommended that Santa trains his strength
      and balance before Christmas and also to avoid filling his sack with more than
      20kg of presents. Also, cognitive training may help to improve his dual task
      performance. 

PMID- 25766045
TI  - Patient reported outcome in posttraumatic pituitary deficiency: results from The
      Danish National Study on posttraumatic hypopituitarism.
AB  - OBJECTIVE: Posttraumatic pituitary hormone deficiency is often suggested. The
      impact of these predominantly mild and often irreproducible deficiencies on
      outcome is less clear. The aim of the present study was to describe patient
      reported outcome in a national a priori unselected cohort of patients with
      traumatic brain injury (TBI) in relation to deficiencies identified upon
      pituitary assessment. DESIGN AND METHODS: We conducted a nationwide population
      based cohort study. Participants were Danish patients with a head trauma
      diagnosis recorded in the Danish Board of Health diagnostic code registry; 439
      patients (and 124 healthy controls) underwent assessment of anterior pituitary
      function 2.5 years (median) after TBI. Questionnaires on health-related quality
      of life (QoL) (SF36, EuroQoL-5D, QoL assessment of GH deficiency in adults) and
      fatigue (MFI-20) were completed in parallel to pituitary assessment. RESULTS:
      Patients with TBI had significant detriments in QoL. Impairment (mainly physical
      scales) related to pituitary deficiency, although only partially confirmed after
      adjustment for demographic differences. Hypogonadotropic hypogonadism related to
      several QoL scores. Increasing impairments were observed with declining total
      testosterone concentrations (men), but not free testosterone concentrations or
      any other hormone concentrations. Total testosterone was not independently
      related to impaired QoL and fatigue, after adjustment for demographics, and
      treatment with antidiabetics, opioids, antidepressants, and anticonvulsants.
      CONCLUSIONS: Only a very limited relationship between pituitary hormone
      deficiencies and QoL/fatigue was demonstrated. Due to the dominating influence of
      concurrent comorbidities, pituitary deficiencies were not independently related
      to QoL/fatigue. Causality is still to be shown, and whether substitution therapy
      could be of additional relevance in selected patients needs to be proven.

PMID- 25766046
TI  - Clinical risk factors of postoperative hyperkalemia after adrenalectomy in
      patients with aldosterone-producing adenoma.
AB  - OBJECTIVE: Unilateral adrenalectomy is the first-line treatment for aldosterone
      producing adenomas (APA). Hyperkalemia after adrenalectomy because of
      contralateral zona glomerulosa insufficiency has been reported. We investigated
      clinical risk factors to predict postoperative hyperkalemia in patients with APA
      undergoing adrenalectomy. DESIGN AND METHODS: This study was conducted by
      retrospectively reviewing medical records from 2000 to 2012 at Seoul National
      University Hospital and two other tertiary centers. Data from 124 patients who
      underwent adrenalectomy were included. Hyperkalemia was defined as serum
      potassium >5.5 mmol/l. Clinical preoperative risk factors included age, blood
      pressure, plasma renin activity (PRA), plasma aldosterone concentration (PAC),
      serum potassium, serum creatinine, glomerular filtration rate (GFR), the mass
      size on pathology, and mineralocorticoid receptor (MR) antagonist use. RESULTS:
      Out of 124 patients, 13 (10.5%) developed postoperative hyperkalemia. The
      incidences of transient and persistent hyperkalemia were 3.2 and 7.3%
      respectively. Preoperative PRA and PAC were not significantly different in
      postoperative hyperkalemic patients compared with normokalemic patients. Patients
      with persistent hyperkalemia were older, had a longer duration of hypertension,
      larger mass size on pathology, and lower GFR (all P<0.05). The incidence of
      postoperative hyperkalemia was not different between MR antagonist users and non
      users. CONCLUSION: Older age (>=53 years), longer duration of hypertension (>=9.5
      years), larger mass size on pathology (>=1.95 cm), and impaired preoperative
      renal function (GFR <58.2 ml/min) were associated with prolonged postoperative
      hyperkalemia in patients with APA. MR antagonist use did not prevent
      postoperative hyperkalemia.

PMID- 25766048
TI  - eta(3) -Allyl coordination at tin(II)-reactivity towards alkynes and
      benzonitrile.
AB  - We herein report the synthesis and characterization of a terphenyl-substituted
      Sn(II) allyl compound featuring an eta(3)  coordination mode in solution and in
      the solid state. Two examples for the interesting reactivity of the allyl Sn(II)
      molecule are presented: Reactions with terminal alkynes result in the formation
      of tricyclic compounds by C?C bond formation and the dimerization of two Sn
      moieties whereas the reaction with benzonitrile leads to a sixteen-membered ring
      system through C?H activation. 

PMID- 25766047
TI  - Triiodothyronine-predominant Graves' disease in childhood: detection and
      therapeutic implications.
AB  - OBJECTIVE: To assess in a pediatric population, the clinical characteristics and
      management of triiodothyronine-predominant Graves' disease (T3-P-GD), a rare
      condition well known in adults, but not previously described in children. DESIGN:
      We conducted a university hospital-based observational study. METHODS: All
      patients with GD followed for more than 1 year between 2003 and 2013 (n=60) were
      included. T3-P-GD (group I) was defined as high free T3 (fT3) concentration (>8.0
      pmol/l) associated with a normal free thyroxine (fT4) concentration and
      undetectable TSH more than 1 month after the initiation of antithyroid drug (ATD)
      treatment. Group II contained patients with classical GD without T3-P-GD.
      RESULTS: Eight (13%) of the patients were found to have T3-P-GD, a median of 6.3
      (3.0-10.5) months after initial diagnosis (n=4) or 2.8 (2.0-11.9) months after
      the first relapse after treatment discontinuation (n=4). At GD diagnosis, group I
      patients were more likely to be younger (6.8 (4.3-11.0) vs 10.7 (7.2-13.7) years)
      and had more severe disease than group II patients, with higher serum TSH
      receptor autoantibodies (TRAb) levels: 40 (31-69) vs 17 (8-25) IU/l, P<0.04, and
      with slightly higher serum fT4 (92 (64-99) vs 63 (44-83) pmol/l) and fT3 (31 (30
      46) vs 25 (17-31) pmol/l) concentrations. During the 3 years following T3-P-GD
      diagnosis, a double dose of ATD was required and median serum fT4:fT3 ratio
      remained lower in group I than in group II. CONCLUSION: Severe hyperthyroidism,
      with particularly high TRAb concentrations at diagnosis, may facilitate the
      identification of patients requiring regular serum fT3 determinations and
      potentially needing higher doses of ATD dosage during follow-up.

PMID- 25766049
TI  - Influence of playing style on the physiological responses of offensive players in
      table tennis.
AB  - AIM: The study aimed to analyse the influence of playing style on the
      physiological responses of offensive players and on match characteristics during
      table tennis matches. METHODS: Eight table tennis players were involved in the
      study. Among them, six players with an offensive playing style (Off) played
      respectively two matches: one against an offensive player (Off vs. Off matches)
      and the other one against a defensive opponent (Off vs. Def matches). Duration of
      rally (DR), real playing time (RPT), effective playing time (EPT), frequency of
      shots by minutes, and shots per rally were measured. Heart rate (HR) was
      monitored continuously while rating of perceived exertion (RPE) was obtained
      after each match. Blood lactate concentrations ([La]) were measured both at the
      end of each set and at the end of the match. RESULTS: DR (5.4+/-0.7 s vs. 3.2+/
      0.4 s), RPT, EPT (31.8+/-5.0% vs. 20.3+/-1.7%), shots per rally (6.6+/-0.9 vs.
      4.6+/-0.9), HRmean (146.0+/-5.9 bpm vs. 139.9+/-9.0 bpm), HRmean relative to the
      predicted maximal HR (HRmax-p) (74.8+/-4.0% vs. 71.7+/-4.3%) and RPE (7.0+/-1.1
      vs. 5.5+/-1.5) were significantly higher (P<0.05) in Off vs. Def matches. No
      significant differences (P>0.05) for HRpeak, [La]mean and [La]peak were noticed
      between Off vs. Def matches and Off vs. Off matches. CONCLUSIONS: Table tennis
      playing style influences match characteristics and the offensive player's
      physiological responses.

PMID- 25766050
TI  - Does running with or without diet changes reduce fat mass in novice runners? A 1
      year prospective study.
AB  - BACKGROUND: The aim of this study was to explore how average weekly running
      distance, combined with changes in diet habits and reasons to take up running,
      influence fat mass. METHODS: Fat mass was assessed by bioelectrical impedance at
      baseline and after 12 months in 538 novice runners included in a 1-year
      observational prospective follow-up study. During follow-up, running distance for
      each participant was continuously measured by GPS while reasons to take up
      running and diet changes were assessed trough web-based questionnaires. Loss of
      fat mass was compared between runners covering an average of 5 km or more per
      week and those running shorter distances. RESULTS: Runners who took up running to
      lose weight and ran over 5 km per week in average over a one-year period combined
      with a diet change reduced fat mass by -5.58 kg (95% CI: -8.69; -2.46; P<0.001).
      Compared with subjects also running over 5 km per week but without diet changes,
      the mean difference in fat mass between groups was 3.81 kg (95% CI: -5.96; -1.66;
      P<0.001). A difference of -3.55 kg (95% CI: -5.69; -1.41; P<0.001) was found when
      comparing with those running less than 5 km per week and making changes to their
      own diet. CONCLUSIONS: An average running distance of more than 5 km per week in
      runners who took up running to lose weight combined with a targeted diet change
      seems effective in reducing fat mass over a one-year period among novice runners.
      Still, randomized controlled trials are needed to better document the effects of
      self-selected diet changes.

PMID- 25766051
TI  - Physical activity, lipid profiles and leptin.
AB  - BACKGROUND: Physical activity and the component of body composition can determine
      lipid profiles and Leptin concentration plasma. METHOD: Thirty-two untrained
      females (20-25 yrs.) (aged 20.9+/-.33 y, weight 57.50+/-7.52 Kg, height 159.56+/
      4.97 cm, and BMI 22.55 +/-2.51 kg.m-2), participated in our study. They randomly
      were divided into two equal groups, trained and control group (N.=16). The
      trained group was assigned to a five week aerobic training program (three
      times/week), with intensity 60-70% HRR (heart rate reserve). The control group
      continued their normal lifestyle. Body weight (BW) was measured. Body fat percent
      (FP) and fat mass (FM), and fat free mass (FFM) were assessed, also the
      concentration of high density lipoprotein (HDL), low density lipoprotein (LDL),
      triglycerides (TG), total cholesterol (TC), and leptin were measured. RESULTS:
      Analysis of covariance (ANCOVA) indicated that BW (F=4.20, P=0.05) significantly
      decreased and HDL (F=43.32, P=0.01) significantly increased in the trained group
      (P-value<0.05), whereas we had no significant difference in BMI, FP, FM, FFM, and
      the serum concentration of LDL, TG, TC, and Leptin between groups and time *
      group interaction, after the five weeks aerobic training period (P<0.05).
      CONCLUSIONS: These results suggest the five-week moderate- intensity aerobic
      training had significant changes in BW and HDL in young female, but had no
      significant impact on BMI, FP, FM, FFM, LDL, TG, TC, and Leptin concentration,
      which are required to increase duration or increase the intensity of physical
      activity.

PMID- 25766052
TI  - Effects of seven weeks of static hamstring stretching on flexibility and sprint
      performance in young soccer players according to their playing position.
AB  - BACKGROUND: The aim of this study was to investigate the effect of 7 weeks of
      static hamstring stretching on flexibility and sprint performance in young soccer
      players. METHODS: One hundred and three healthy soccer players voluntarily
      participated in this study. Subjects were assigned to a control group (N.=22,
      16.5+/-0.7 years, 174.0+/-5.4 cm and 68.0+/-6.8 kg) and an experimental group
      (N.=81, 18.9+/-1.8 years, 176.0+/-5.8 cm and 68.2+/-8.4 kg). All subjects
      performed a sit-and-reach and a 30-m Sprint Test to assess their flexibility
      performance and sprinting ability, respectively, before and after 7 weeks of
      static hamstring stretching program. The static stretching program consisted of 4
      stretching exercises performed at the end of the training session during 6 days
      per week. Each stretch was held for 30-s and performed twice with a 15-s rest
      between. RESULTS: Flexibility was significantly (P<0.05) improved for the
      experimental group. This improvement was analyzed in all playing positions
      studied. There were significant differences (P<0.05) between pre and post 30-m
      Sprint Test in both groups. All soccer positions significantly (P<0.05) improved
      their performance in the experimental group. However, in the control group only
      defenders improved significantly (P<0.05) the sprint time. CONCLUSIONS: The use
      of static stretching at the end of the training sessions prevents the negative
      effect of the load on hamstring flexibility and it can influence improvement in
      flexibility.

PMID- 25766053
TI  - Efficacy of inertial training in elbow joint muscles: influence of different
      movement velocities.
AB  - BACKGROUND: The aim of this study was to evaluate the influence of inertial
      training performed with different movement velocities on elbow flexor and
      extensor strength and power. METHODS: Thirty-eight male physical education
      students were divided into training and control groups. The two training groups
      performed inertial training three times per week for five weeks using the
      Inertial Training Measurement System. Elbow joint flexors and extensors were
      trained using different maximal movement velocities: 7.50 rad.s(-1) in the faster
      (TF) group and 5.76 rad.s(-1) in the slower (TS) group. Before and after
      training, we evaluated maximum force and power of elbow flexors and extensors
      muscles under training conditions, maximum torque and power of elbow flexors and
      extensors muscles under isokinetic conditions and maximal power output achieved
      during upper body Ergometer Test. RESULTS: Training induced significant increases
      in elbow flexor force (28.4% in TF and 13.7% in TS) and power (37.7% in TF and
      12.4% in TS) measured under training conditions. However, changes in the elbow
      flexors in the TF group were greater than in the TS group. Elbow extensor force
      and power measured under inertial conditions increased significantly only in the
      TF group; 12.5% and 21.1%, respectively. Moreover, the EMG amplitude of the
      biceps brachii and triceps brachii and upper limb muscle mass increased in both
      training groups. Measurements made under isokinetic conditions indicated that
      torque and power improved only in the elbow flexors, no changes in maximal power
      output were observed during the upper limb Ergometer Test. CONCLUSIONS: The short
      term inertial training resulted in significant elbow muscles strength and power
      improvements. ITMS training induced also the increase of upper limbs muscle mass
      and the increase of EMG activity of muscles during flexion and extension of
      elbow. Moreover, greater movement velocities seem to be a benefit for strength
      and power enhancement. However, further studies are needed to confirm this
      suggestion.

PMID- 25766054
TI  - Dynamics of heart rate variability at different ages: effect of the arm crank and
      cycle ergometer protocols.
AB  - BACKGROUND: The aim of this study was to compare the behavior of heart rate
      variability at rest, mid-test, immediately, 5 and 10 min of recovery following
      the exhaustive arm crank and cycle ergometer protocols in healthy children,
      middle-aged and elderly subjects. METHODS: Thirty-six healthy men volunteered to
      participate in this study and were assigned to three groups: child (N.=12),
      middle-aged (N.=12) and elder (N.=12). Heart rate variability was assessed by
      calculation of the mean R-R interval measured by Electrocardiogram at each
      phases. RESULTS: Heart rate variability significantly decreased at mid-test,
      immediately and significantly increased in 5 and 10 min of recovery after both
      the arm crank and cycle ergometer protocols among all groups, these changes were
      significantly higher in cycle ergometer compared with arm crank protocol among
      all age groups. Moreover, increase of heart rate variability was significantly
      higher in the middle-aged than that for children and elder subjects during 5 and
      10 min of recovery after cycle ergometer protocol. CONCLUSIONS: Our results
      indicate a relationship between lowered heart rate variability and the age of the
      subjects. In addition, our findings suggest a clinically important effect of
      exhaustive physical activity in various ages after upper body work than lower
      body work.

PMID- 25766055
TI  - Acting on black box warnings requires a GRADE evidence table and an
      implementation guide: the case of teriparatide.
AB  - OBJECTIVES: To assess how well do the black box warnings present and communicate
      evidence in a way that is consistent with evidence-based patient-centered
      practice, through evaluating the boxed warning on teriparatide-induced
      osteosarcoma. STUDY DESIGN AND SETTING: We critically appraised teriparatide
      black box warning for osteosarcoma by reviewing human and animal studies that
      were used as basis for the warning. We also evaluated the quality of the evidence
      using the Grading of Recommendations Assessment, Development and Evaluation
      framework. RESULTS: We found that this warning was based on very low-quality
      evidence that was derived primarily from animal studies. The quality of evidence
      was rated down because of high risk of bias in addition to inconsistency,
      indirectness, and imprecision of the estimates. The warning does not provide
      sufficient guidance for practice like an implementation tool or an evidence
      profile to clarify the limitations of the evidence. CONCLUSION: Black box warning
      for teriparatide-associated osteosarcoma does not explicitly present the quality
      of evidence, and therefore, it could be of limited use in evidence-based
      practice. We propose that black box warnings should include an evidence profile
      and an implementation guide to be more useful in evidence-based patient-centered
      practice.

PMID- 25766056
TI  - Librarian co-authors correlated with higher quality reported search strategies in
      general internal medicine systematic reviews.
AB  - OBJECTIVES: To determine whether librarian and information specialist authorship
      was associated with better reported systematic review (SR) search quality. STUDY
      DESIGN AND SETTING: SRs from high-impact general internal medicine journals were
      reviewed for search quality characteristics and reporting quality by independent
      reviewers using three instruments, including a checklist of Institute of Medicine
      Recommended Standards for the Search Process and a scored modification of the
      Peer Review of Electronic Search Strategies instrument. RESULTS: The level of
      librarian and information specialist participation was significantly associated
      with search reproducibility from reported search strategies (Chi(2) = 23.5; P <
      0.0001). Librarian co-authored SRs had significantly higher odds of meeting 8 of
      13 analyzed search standards than those with no librarian participation and six
      more than those with mentioned librarian participation. One-way ANOVA showed that
      differences in total search quality scores between all three groups were
      statistically significant (F2,267 = 10.1233; P < 0.0001). CONCLUSION: Problems
      remain with SR search quality and reporting. SRs with librarian or information
      specialist co-authors are correlated with significantly higher quality reported
      search strategies. To minimize bias in SRs, authors and editors could encourage
      librarian engagement in SRs including authorship as a potential way to help
      improve documentation of the search strategy.

PMID- 25766057
TI  - Quality of evidence is a key determinant for making a strong GRADE guidelines
      recommendation.
AB  - OBJECTIVES: The objective of the study was to assess the association between
      Grading of Recommendations Assessment, Development and Evaluation (GRADE) factors
      and the strength of recommendations. STUDY DESIGN AND SETTING: The study was
      conducted as part of the development of clinical practice guideline (CPG) by
      American Association of Blood Banking related to role of prophylactic vs.
      therapeutic transfusion for the management of thrombocytopenia. The association
      between GRADE factors and strength of recommendations was assessed using logistic
      regression and multilevel mixed effect logistic regression model. RESULTS:
      Seventeen members of the CPG panel participated in the recommendation process.
      The quality of evidence was the only statistically significant (odds ratio = 4.5;
      P < 0.001) GRADE factor associated with the strength of recommendations. The
      predictive model showed that there is about 90% probability that panelists would
      issue the same (strong) recommendation when confidence in the effects of
      intervention is high vs. 10% when the quality of evidence is very low.
      CONCLUSION: The results showed that quality of evidence is a key determinant for
      making a strong vs. a weak recommendation.

PMID- 25766058
TI  - Reactive and Inelastic Channels in the Ca*...FCH3 Transition State: A Simple
      Branching Mechanism.
AB  - To study the excited state dynamics between a calcium atom and the CH3F molecule,
      a Ca...CH3F 1:1 complex has been prepared by a supersonic expansion with laser
      ablation of calcium metal in the gas phase. Tunable laser excitation of these
      complexes in molecular states correlating to Ca (1)P1(4s4p) + CH3F allows
      observing two competitive channels: the direct dissociation and the reactive
      channel into CaF* + CH3. The translational recoil, as well as the alignment of
      the fragments Ca* and CaF* have been analyzed by velocity map imaging and time-of
      flight mass spectrometry. This revealed that both the dissociation and reaction
      processes are quasi direct and are of comparable intensity. We provide a simple
      interpretation for this process: the electronically excited potential surface of
      the Ca*...FCH3 complex initiates a fast predissociation from a suspended well to
      two repulsive surfaces that lead either to Ca (1)P1(4s4p) (Omega = 1) + CH3F or
      to CaF((2)Delta) + CH3. 

PMID- 25766059
TI  - Apes in the Anthropocene: flexibility and survival.
AB  - We are in a new epoch, the Anthropocene, and research into our closest living
      relatives, the great apes, must keep pace with the rate that our species is
      driving change. While a goal of many studies is to understand how great apes
      behave in natural contexts, the impact of human activities must increasingly be
      taken into account. This is both a challenge and an opportunity, which can
      importantly inform research in three diverse fields: cognition, human evolution,
      and conservation. No long-term great ape research site is wholly unaffected by
      human influence, but research at those that are especially affected by human
      activity is particularly important for ensuring that our great ape kin survive
      the Anthropocene. 

PMID- 25766060
TI  - Righting the resource management ship: a response to Grose.
AB  - Absolute certainty is a luxurious state that is seldom attained by competent
      decision makers. Natural resource managers are accountable to the public for high
      stakes actions that have incompletely understood consequences, so there is little
      tolerance for error. I argue that the traditional tools of science and decision
      theory are both necessary and sufficient, despite recent 'backwards thinking' on
      this topic. 

PMID- 25766061
TI  - Empirical support for different types of positive mortality effects. A reply to
      Abrams.

PMID- 25766062
TI  - Medication safety activities of hospital pharmacists in Ghana; challenges and
      perceived impact on patient care.
AB  - BACKGROUND: Pharmacists by their training have the competences and skills to
      promote safe use of medicines which is an essential component of patient safety.
      This study explored the perceptions of hospital pharmacists' role in medication
      safety in Ghana, identified their attendant challenges and ways of enhancing such
      roles in the future. METHOD: A self-administered questionnaire was delivered to
      200 pharmacists selected conveniently from the 10 regions of Ghana. Questions in
      the questionnaire were based on a systematic literature review that had
      catalogued and summarised all the activities of hospital pharmacists related to
      medication safety. RESULTS: A total of 176 (88% response rate) questionnaires
      were completed and returned. Almost all pharmacists (97.7%) believed that they
      were involved in medication safety activities in their daily routine. The
      frequently performed activities were counselling of out-patient (91.8%), training
      pharmacy and other clinical students (72.2%), reporting on medication errors
      (70%), and reconciling medications (69.2%). The mean weekly time spent on the
      activities ranged from 6.5 to 19.8 hours. Participants who had clinical pharmacy
      related additional qualifications (chi2 = 37.749; p = 0.049) and worked in
      tertiary care hospitals (chi2 = 26.6; p = 0.377) undertook more medication safety
      activities than those without. The cited challenges faced by participants
      included inadequate time available (62.7%), spending most time in managerial
      activities (47.3%), lack of formal structures of engagement (43.8%), lack of
      motivation by superiors (34.9%), and no formal schedule by supervisor (32%). Only
      7.7% stated they lack interest in performing those activities. CONCLUSIONS:
      Pharmacists undertake many medication safety activities routinely that they
      perceive to have impact on patient care outcomes. Restructuring of their
      managerial roles will contribute to freeing time for pharmacists to engage more
      in those activities.

PMID- 25766063
TI  - Application of the IHI Global Trigger Tool in measuring the adverse event rate in
      a Turkish healthcare setting.
AB  - BACKGROUND: The goal of this study was to measure an adverse event rate and
      determine the potential usefulness of the Institute for Healthcare Improvement's
      Global Trigger Tool (GTT). Besides using the GTT to measure the adverse event
      rate, a comparison was also made with the internal Voluntary Reporting
      Notification System (VRNS) to identify and compare the strengths and weaknesses
      of the two approaches. METHOD: Retrospective data were collected from reported
      patient safety incidents covering a one-year period at Duzce University Hospital,
      Turkey. Using a range of selection criteria, a total of 219 patient records were
      selected and then reviewed by a trained GTT team, to investigate the positive
      triggers in the content of the patient records. RESULTS: It was determined that
      adverse events per 1000 patient days totalled 80.72. Adverse events per 100
      admissions were 29.39, and the rate of admissions with adverse events was 16.67%.
      The comparison between the GTT and the VRNS showed that the GTT is 19 times more
      sensitive than the VRNS in the adverse event evaluation process. CONCLUSION: This
      is the first published study of the rate of adverse events in a Turkish
      healthcare setting using the GTT. It was found that the GTT was applicable in
      this setting, yielding more accurate measurement of the adverse event rate.
      However, the content of the GTT should be adjusted regarding the standards and
      documentations used in the Turkish healthcare system to be more useful.

PMID- 25766064
TI  - Measuring ward round quality in urology.
AB  - BACKGROUND: Ward rounds are the traditional process by which clinical information
      is interpreted and management plans made in the inpatient setting and the only
      time during which patient-doctor interaction can reliably occur. Efforts to
      improve quality and safety have started looking at the ward round but this has
      mainly been in the acute medical setting. OBJECTIVE: To begin the quality
      improvement process for Urological ward rounds. METHODS: Twenty indicators
      thought to relate to quality were recorded for every weekday ward round by the
      Urology team for one month. RESULTS: Twenty ward rounds, 93 patient encounters,
      were reviewed. A consultant was present for 37% of the patient encounters. 84% of
      observation charts were reviewed; drug charts 28% and antibiotics 70%. Plans were
      communicated to the doctors, patient and nursing staff. All notes were typed
      directly onto the electronic system, 20% of notes were checked by the lead
      clinician. Mean time per patient was 6 minutes. CONCLUSIONS: By starting a
      discussion about ward rounds we aim to align the process with the broader values
      of the organisation. Ward rounds can be the cornerstone of delivering safe, clean
      and personal care and measuring this process is vital to understanding efforts to
      improve them.

PMID- 25766065
TI  - Atomic bomb testing and its effects on global male to female ratios at birth.
AB  - AIMS: Fallout from atomic bomb testing may travel great distances before
      precipitating. Males are born in excess of females in a ratio that approximates
      0.515 (M/T: male live births divided by total live births. Radiation increases
      M/T by causing lethal malformations that affect female more than male foetuses,
      decreasing total births. This study was carried out in order to ascertain whether
      the effects of increased background radiation levels from atomic weapon testing
      had any widespread effects on M/T and births in the Americas, Europe, Asia and
      Australasia in relation to the Partial Test Ban Treaty of 1963. METHODS: Annual
      live births by gender were obtained from a World Health Organization dataset and
      annual number of atomic bomb tests were also obtained (historical data). RESULTS:
      Overall, 94.5% of births studied showed a uniform reduction in M/T between the
      early 1950s to the late 1960s, followed by an increase to the mid-1970s, with a
      subsequent decline. A negative correlation of M/T with total births was found in
      66% of births studied, and these were the regions which exhibited the rising M/T
      pattern in the 1970s. The birth deficit for countries with significant
      correlations of total births with M/T (North America, Europe and Asia) was
      estimated at 10090701. CONCLUSIONS: A rising M/T was found in most regions in
      temporal association with atomic weapon testing. Most of these regions also had
      an associated decline in total births. Elevated levels of man-made ambient
      radiation may have reduced total births, affecting pregnancies carrying female
      pregnancies more than those carrying male pregnancies, thereby skewing M/T toward
      a higher male proportion.

PMID- 25766066
TI  - Is off-label use a risk factor for adverse drug reactions in pediatric patients?
      A prospective study in an Indian tertiary care hospital.
AB  - BACKGROUND: The lack of specific medicines and labeling recommendations for the
      pediatric population is a long-standing problem. Using data from an observational
      study of adverse drug reactions (ADRs) among pediatric inpatients, we aimed to
      test the hypothesis that off-label status is a risk factor for ADRs. METHODS: A
      prospective intensive surveillance was conducted at a pediatric ward of a public
      teaching hospital. Adverse events to labeled and off-label use were assessed for
      incidence, severity and predictors. A multivariate Cox proportional hazards
      regression model used to assess off-label use is a risk factor for ADR occurring.
      RESULTS: Off-label and labeled use were responsible for 34 (67%) and 17 (33%)
      ADRs respectively. Medicines which lacked complete pediatric labeling had the
      greatest odds for ADRs (9.21% of medicines in this category were implicated, OR
      2.84 (95% CI 1.37-7.09). Number of off-label medicines given to patient
      significantly increased the hazard of an ADR (hazard ratio (HR) 1.28, 95% CI 0.43
      3.78, P = 0.002). Number of medicines given also significantly increased the
      hazard (HR 1.2, 95% CI 0.80-1.71, P < 0.001). CONCLUSIONS: Use of off-label
      medicines were more likely to be implicated in an ADR than labeled medicines.
      This off-label use would be acceptable if evidence of potential benefits
      outweighs ADRs risk.

PMID- 25766067
TI  - The role of chondroitinase as an adjuvant to peripheral nerve repair.
AB  - Chondroitin sulfate proteoglycans (CSPGs) are potent inhibitors of neural
      regeneration in the peripheral nervous system. Following nerve injury, inhibitory
      CSPGs accumulate within the endoneurium and Schwann cell basal lamina of the
      distal nerve stump. The utilization of chondroitinase ABC (chABC) has led to a
      marked increase in the ability of injured axons to regenerate across gaps through
      the CSPG-laden extracellular matrix. Experimental models have repeatedly shown
      chABC to be capable of degrading the CSPGs that hinder neurite outgrowth. In this
      article, the characterization of CSPGs, their upregulation following peripheral
      nerve injury, and potential mechanisms behind their growth and inhibition are
      described. To date, the literature supports that the adjunct use of chABC may be
      beneficial to peripheral nerve repair in digesting inhibitory CSPGs. chABC has
      also shown some indication of synergism with other therapies, such as stem cell
      transplantation. Evidence supporting the use of chondroitinase as a treatment
      modality in nerve repair, either alone or in combination with other agents, is
      reviewed within. Finally, several shortcomings of chABC are addressed, notably
      its thermal stability and physiologic longevity - both hindering its widespread
      clinical adoption. Future studies are warranted in order to optimize the
      therapeutic benefits of the chondroitinase enzyme.

PMID- 25766069
TI  - Opioid use and lactation: protecting the child in the context of maternal pain
      care.

PMID- 25766068
TI  - Blood cell transcriptomic-based early biomarkers of adverse programming effects
      of gestational calorie restriction and their reversibility by leptin
      supplementation.
AB  - The challenge of preventing major chronic diseases requires reliable, early
      biomarkers. Gestational mild undernutrition in rats is enough to program the
      offspring to develop later pathologies; the intake of leptin, a breastmilk
      component, during lactation may reverse these programming effects. We used these
      models to identify, in peripheral blood mononuclear cells (PBMCs), transcriptomic
      based early biomarkers of programmed susceptibility to later disorders, and
      explored their response to neonatal leptin intake. Microarray analysis was
      performed in PBMCs from the offspring of control and 20% gestational calorie
      restricted dams (CR), and CR-rats supplemented with physiological doses of leptin
      throughout lactation. Notably, leptin supplementation normalised 218 of the 224
      mRNA-levels identified in PBMCs associated to undernutrition during pregnancy.
      These markers may be useful for early identification and subsequent monitoring of
      individuals who are at risk of later diseases and would specifically benefit from
      the intake of appropriate amounts of leptin during lactation. 

PMID- 25766070
TI  - Effect of low carbohydrate high protein (LCHP) diet on lipid metabolism, liver
      and kidney function in rats.
AB  - The objective of this study was to compare effects of Western diet (WD) with low
      carbohydrate high protein (LCHP) diet on lipid metabolism, liver and kidney
      function in rats. Eighteen rats were randomly assigned to three experimental
      groups and fed for the next 2 months. The experimental diets were: Control (7% of
      soybean oil, 20% protein), WD (21% of butter, 20% protein), and LCHP (21% of
      butter and 52.4% protein) diet. The LCHP diet significantly decreased the body
      weight of the rats. Diet consumption was differentiated among groups, however
      significant changes were observed since third week of the experiment duration.
      Rats fed LCHP diet ate significantly less (25.2g/animal/day) than those from
      Control (30.2g/animal/day) and WD (27.8 g/animal/day) groups. Additionally, food
      efficiency ratio (FER) tended to decrease in LCHP fed rats. Serum homocysteine
      concentration significantly decreased in rats fed WD and LCHP diets. Liver
      weights were significantly higher in rats fed WD and LCHP diets. At the end of
      the experiment (2 months) the triacylglycerol (TAG) was significantly decreased
      in animals fed LCHP compared to WD. qRT-PCR showed that SCD-1 and FAS were
      decreased in LCHP fed rats, but WD diet increased expression of lipid metabolism
      genes. Rats receiving LCHP diet had two fold higher kidney weight and 54.5%
      higher creatinin level compared to Control and WD diets. In conclusion, LCHP diet
      decreased animal's body weight and decreased TAG in rat's serum. However, kidney
      damage in LCHP rats was observed.

PMID- 25766071
TI  - Pharmaceutical integrated stress response enhancement protects oligodendrocytes
      and provides a potential multiple sclerosis therapeutic.
AB  - Oligodendrocyte death contributes to the pathogenesis of the inflammatory
      demyelinating disease multiple sclerosis (MS). Nevertheless, current MS therapies
      are mainly immunomodulatory and have demonstrated limited ability to inhibit MS
      progression. Protection of oligodendrocytes is therefore a desirable strategy for
      alleviating disease. Here we demonstrate that enhancement of the integrated
      stress response using the FDA-approved drug guanabenz increases oligodendrocyte
      survival in culture and prevents hypomyelination in cerebellar explants in the
      presence of interferon-gamma, a pro-inflammatory cytokine implicated in MS
      pathogenesis. In vivo, guanabenz treatment protects against oligodendrocyte loss
      caused by CNS-specific expression of interferon-gamma. In a mouse model of MS,
      experimental autoimmune encephalomyelitis, guanabenz alleviates clinical
      symptoms, which correlates with increased oligodendrocyte survival and diminished
      CNS CD4+ T cell accumulation. Moreover, guanabenz ameliorates relapse in
      relapsing-remitting experimental autoimmune encephalomyelitis. Our results
      provide support for a MS therapy that enhances the integrated stress response to
      protect oligodendrocytes against the inflammatory CNS environment. 

PMID- 25766072
TI  - Pulmonary radiofrequency ablation (Part 1): current state.
AB  - The risks involved in surgical treatment and conventional radiotherapy in
      patients with early lung cancer or lung metastases often make these treatments
      difficult to justify. However, on the other hand, it is also unacceptable to
      allow these lesions to evolve freely because, left untreated, these neoplasms
      will usually lead to the death of the patient. In recent years, alternative local
      therapies have been developed, such as pulmonary radiofrequency ablation, which
      has proven to increase survival with a minimal risk of complications. There are
      common recommendations for these treatments, and although the specific
      indications for using one technique or another have yet to be established, there
      are clearly defined situations that will determine the outcome of the treatment.
      It is important to know these situations, because appropriate patient selection
      is essential for therapeutic success. This article aims to describe the
      characteristics and constraints of pulmonary radiofrequency ablation and to
      outline its role in thoracic oncology in light of the current evidence. 

PMID- 25766074
TI  - Using Measurements of Shunt and Ventilation-to-Perfusion Ratio to Quantify the
      Severity of Bronchopulmonary Dysplasia.
AB  - BACKGROUND: Classifying the severity of bronchopulmonary dysplasia (BPD) by
      continuous numerical variables would facilitate follow-up of disease progression
      and quantified analysis of disease determinants. OBJECTIVES: To non-invasively
      measure oxygenation impairment in BPD by the degree of right-to-left shunt, right
      shift of the oxyhaemoglobin dissociation curve and ventilation/perfusion (VA/Q)
      inequality and to explore their relation with clinical parameters. METHODS:
      Prospective cohort study of 24 infants with a median (interquartile range, IQR)
      gestation of 25 weeks (24-27) and a birth weight of 0.70 kg (0.63-0.93), studied
      at 36 days (30-66), at a postmenstrual age (PMA) of 33 weeks (29-36). Inspired
      oxygen (FIO2) was varied to obtain three to five transcutaneous oxygen saturation
      (SpO2) values between 85 and 96%. Values of shunt, shift and VA/Q were obtained
      by plotting the paired data of SpO2 against FIO2 for each infant using a unique
      program. Right-to-left shunt, right shift of the oxyhaemoglobin dissociation
      curve and VA/Q were measured in infants born <32 weeks PMA receiving oxygen at 28
      days. RESULTS: The median (IQR) shunt was 8% (0.3-16.5), shift 14.5 kPa (10.9
      19.4) and VA/Q 0.40 (0.30-0.48). Shunt, shift and VA/Q were significantly related
      to gestational age (GA) at birth, PMA at study, weight at study and weight gain
      per week. CONCLUSIONS: Severity of pulmonary oxygenation impairment in BPD can be
      quantified at the cot-side by non-invasive measurement of shunt, shift and VA/Q.
      Low GA at birth, low weight at birth and at the time of study and impaired weight
      gain are significantly associated with the severity of oxygen-exchange impairment
      in infants with BPD.

PMID- 25766075
TI  - Role of hydrogen-bonding and its interplay with octahedral tilting in CH3NH3PbI3.
AB  - First principles calculations on the hybrid perovskite CH3NH3PbI3 predict strong
      hydrogen-bonding which influences the structure and dynamics of the
      methylammonium cation and reveal its interaction with the tilting of the PbI6
      octahedra. The calculated atomic coordinates are in excellent agreement with
      neutron diffraction results. 

PMID- 25766073
TI  - A metabolite of Danshen formulae attenuates cardiac fibrosis induced by
      isoprenaline, via a NOX2/ROS/p38 pathway.
AB  - BACKGROUND AND PURPOSE: Cardiac fibrosis is a common feature of advanced coronary
      heart disease and is characteristic of heart disease. However, currently
      available drugs against cardiac fibrosis are still very limited. Here, we have
      assessed the role of isopropyl 3-(3,4-dihydroxyphenyl)-2-hydroxylpropanoate
      (IDHP), a new metabolite of Danshen Dripping Pills, in cardiac fibrosis mediated
      by the beta-adrenoceptor agonist, isoprenaline, and its underlying mechanisms.
      EXPERIMENTAL APPROACH: Identification of IDHP was identified by mass
      spectrometry, and proton and carbon nuclear magnetic resonance spectra.
      Myocardial collagen was quantitatively assessed with Picrosirius Red staining.
      Expression of mRNA for collagen was evaluated with real-time PCR. Phosphorylated
      and total p38 MAPK, NADPH oxidase (NOX) and superoxide dismutase (SOD) were
      analysed by Western blot. Generation of reactive oxygen species (ROS) generation
      was evaluated by dihydroethidium (DHE) fluorescent staining. NOX2 was knocked
      down using specific siRNA. KEY RESULTS: IDHP attenuated beta-adrenoceptor
      mediated cardiac fibrosis in vivo and inhibited isoprenaline-induced
      proliferation of neonatal rat cardiac fibroblasts (NRCFs) and collagen I
      synthesis in vitro. Phosphorylation of p38 MAPK, which is an important mediator
      in the pathogenesis of isoprenaline-induced cardiac fibrosis, was inhibited by
      IDHP. This inhibition of phospho-p38 by IDHP was dependent on decreased
      generation of ROS. These effects of IDHP were abolished in NRCFs treated with
      siRNA for NOX2. CONCLUSIONS AND IMPLICATIONS: IDHP attenuated the cardiac
      fibrosis induced by isoprenaline through a NOX2/ROS/p38 pathway. These novel
      findings suggest that IDHP is a potential pharmacological candidate for the
      treatment of cardiac fibrosis, induced by beta-adrenoceptor agonists.

PMID- 25766078
TI  - Nanocarrier-based interventions for the management of MDR/XDR-TB.
AB  - Emergence of multidrug-resistant TB (MDR-TB) and extensively drug-resistant TB
      over the past decade presents an unprecedented public health challenge to which
      countries of concern are responding far too slowly. Global Tuberculosis Report
      2014 marks the 20th anniversary of the Global Project on Anti-Tuberculosis Drug
      Resistance Surveillance, indicating the highest global level of drug-resistance
      ever recorded detection of 97 000 patients with MDR-TB resulting in 170 000
      deaths in 2013. Treatment of MDR-TB is expensive, complex, prolonged (18-24
      months) and associated with a higher incidence of adverse events. In this
      context, nanocarrier delivery systems (NDSs) efficiently encapsulating
      considerable amounts of second-line anti tubercular drugs ((s)ATDs), eliciting
      controlled, sustained and more profound effect to trounce the need to administer
      (s)ATDs at high and frequent doses, would assist in improving patient compliance
      and avoid hepatotoxicity and/or nephrotoxicity/ocular toxicity/ototoxicity
      associated with the prevalent (s)ATDs. Besides, NDSs are also known to inhibit
      the P-glycoprotein efflux, reduce metabolism by gut cytochrome P-450 enzymes and
      circumnavigate the hepatic first-pass effect, facilitating absorption of drugs
      via intestinal lymphatic pathways. This review first provides a holistic account
      on MDR-TB and discusses the molecular basis of Mycobacterium tuberculosis
      resistance to anti-tubercular drugs. It also provides an updated bird's eye view
      on current treatment strategies and laboratory diagnostic test for MDR-TB.
      Furthermore, a relatively pithy view on patent studies on second-line
      chemotherapy using NDSs will be discussed. 

PMID- 25766079
TI  - Intracellular target delivery of 10-hydroxycamptothecin with solid lipid
      nanoparticles against multidrug resistance.
AB  - The main objective of this study was to design a suitable drug delivery system
      for 10-hydroxycamptothecin (HCPT). In this study, HCPT-loaded solid lipid
      nanoparticle (HCPT-loaded SLN) was successfully prepared. The HCPT-loaded SLN was
      characterized by size, entrapment efficiency and drug release manner. The
      cytotoxicity of HCPT-loaded SLN was assessed in vitro using HepG2/HCPT cells and
      in vivo utilizing human tumor xenograft nude mouse model. HCPT-loaded SLN
      indicated the ability to target HepG2/HCPT cells and accumulated higher drug
      content in HepG2/HCPT cells. HCPT-loaded SLN enhanced the cytotoxicity of HCPT in
      a concentration-dependent manner. Based on these results, HCPT-loaded SLN
      suggested being a promising vehicle for liver-targeted drug delivery. Moreover,
      it can be of clinical interest to overcome multidrug resistance (MDR)
      effectively. 

PMID- 25766080
TI  - The alpha-fetoprotein third domain receptor binding fragment: in search of
      scavenger and associated receptor targets.
AB  - Recent studies have demonstrated that the carboxyterminal third domain of alpha
      fetoprotein (AFP-CD) binds with various ligands and receptors. Reports within the
      last decade have established that AFP-CD contains a large fragment of amino acids
      that interact with several different receptor types. Using computer software
      specifically designed to identify protein-to-protein interaction at amino acid
      sequence docking sites, the computer searches identified several types of
      scavenger-associated receptors and their amino acid sequence locations on the AFP
      CD polypeptide chain. The scavenger receptors (SRs) identified were CD36, CD163,
      Stabilin, SSC5D, SRB1 and SREC; the SR-associated receptors included the mannose,
      low-density lipoprotein receptors, the asialoglycoprotein receptor, and the
      receptor for advanced glycation endproducts (RAGE). Interestingly, some SR
      interaction sites were localized on the AFP-derived Growth Inhibitory Peptide
      (GIP) segment at amino acids #480-500. Following the detection studies, a
      structural subdomain analysis of both the receptor and the AFP-CD revealed the
      presence of epidermal growth factor (EGF) repeats, extracellular matrix-like
      protein regions, amino acid-rich motifs and dimerization subdomains. For the
      first time, it was reported that EGF-like sequence repeats were identified on
      each of the three domains of AFP. Thereafter, the localization of receptors on
      specific cell types were reviewed and their functions were discussed. 

PMID- 25766081
TI  - Effect of the Mediterranean diet on the lipid-lipoprotein profile: is it
      influenced by the family history of dyslipidemia?
AB  - BACKGROUND/AIMS: To examine whether a family history of dyslipidemia influences
      the lipid-lipoprotein response to the Mediterranean diet (MedDiet). METHODS: We
      recruited 36 individuals with a positive family history of dyslipidemia (i.e.
      having at least one first-degree relative with a diagnosis of dyslipidemia) and
      28 individuals with a negative family history of dyslipidemia, aged between 24
      and 53 years, who had slightly elevated low-density lipoprotein cholesterol (LDL
      C) concentrations (3.4-4.9 mmol/l) or a total cholesterol to high-density
      lipoprotein cholesterol (HDL-C) ratio>=5.0. Variables related to the lipid
      lipoprotein profile were measured before and after a 4-week isocaloric MedDiet
      during which all foods and drinks were provided to participants. RESULTS: A group
      by time interaction was noted for plasma total cholesterol concentrations
      (p=0.03), subjects with a negative family history of dyslipidemia having greater
      decreases than those with a positive family history of dyslipidemia (-11.3 vs. 
      5.1%, respectively). Decreases in LDL-C, HDL-C, total cholesterol to HDL-C ratio,
      LDL-C to HDL-C ratio, apo B, apo A-1, apo A-2 and apo B to apo A-1 ratio were
      noted, with no difference between groups (p for group by time interaction>=0.11).
      CONCLUSIONS: Results highlight that inherited susceptibilities to dyslipidemia
      may explain at least in part the heterogeneity in the cholesterol-lowering
      effects of the MedDiet.

PMID- 25766082
TI  - Reflexed Compression Suture for the Management of Atonic Postpartum Hemorrhage
      with an Abnormally Adherent Placenta.
AB  - BACKGROUND/AIMS: Postpartum hemorrhage (PPH) is a life-threatening condition with
      a worldwide occurrence. The purpose of this study is to evaluate the efficacy and
      safety of a reflexed compression suture in controlling severe atonic PPH with
      placenta accreta. METHODS: Eleven women with severe PPH due to uterine inertia or
      placenta accreta were administered the reflexed compression suture. The procedure
      was to reflex the fundus onto the anterior wall of the uterus for compressing
      hemostasis and to form a 'belt-like' binding suture to reinforce the
      effectiveness of pressing the myometrium. RESULTS: Ten of the 11 women (90.9%)
      were successfully treated with the suture, and the uterus was preserved. None of
      these patients developed complications related to this method. Only in 1 patient
      with placenta increta could the bleeding not be stanched, and a peripartum
      hysterectomy was performed. Two women had pregnancies after the suture.
      CONCLUSION: The reflexed compression suture is a simple, swift, safe and
      effective technique of controlling uterine atonic bleeding, particularly in
      patients with an abnormally adherent placenta. The advantage of not having to
      conduct a hysterotomy also lies in reducing the duration of anesthesia and blood
      loss.

PMID- 25766083
TI  - Suppressing side-lobe radiations of horn antenna by loading metamaterial lens.
AB  - We propose a new approach to control the amplitude and phase distributions of
      electromagnetic fields over the aperture of a horn antenna. By loading a
      metamaterial lens inside the horn antenna, a tapered amplitude distribution of
      the aperture field is achieved, which can suppress the side-lobe radiations of
      the antenna. The metamaterial is further manipulated to achieve a flat phase
      distribution on the horn aperture to avoid the gain reduction that usually
      suffers in the conventional low-sidelobe antenna designs. A prototype of the
      metamaterial-loaded horn antenna is designed and fabricated. Both numerical
      simulations and measured results demonstrate the tapered aperture-field
      distribution and significant reduction of side-lobe and back-lobe radiations in
      the operating frequency band. 

PMID- 25766085
TI  - A Stillinger-Weber potential for single-layered black phosphorus, and the
      importance of cross-pucker interactions for a negative Poisson's ratio and edge
      stress-induced bending.
AB  - The distinguishing structural feature of single-layered black phosphorus is its
      puckered structure, which leads to many novel physical properties. In this work,
      we first present a new parameterization of the Stillinger-Weber potential for
      single-layered black phosphorus. In doing so, we reveal the importance of a cross
      pucker interaction term in capturing its unique mechanical properties, such as a
      negative Poisson's ratio. In particular, we show that the cross-pucker
      interaction enables the pucker to act as a re-entrant hinge, which expands in the
      lateral direction when it is stretched in the longitudinal direction. As a
      consequence, single-layered black phosphorus has a negative Poisson's ratio in
      the direction perpendicular to the atomic plane. As an additional demonstration
      of the impact of the cross-pucker interaction, we show that it is also the key
      factor that enables capturing the edge stress-induced bending of single-layered
      black phosphorus that has been reported in ab initio calculations. 

PMID- 25766084
TI  - Efficient ethanol production from potato and corn processing industry waste using
      E. coli engineered to express Vitreoscilla haemoglobin.
AB  - Engineering of ethanologenic E. coli to express the haemoglobin (VHb) from the
      bacterium Vitreoscilla has been shown to enhance ethanol production by
      fermentation of pure sugars, sugars from hydrolysis of lignocellulose, components
      of whey, and sugars from wastewater produced during potato processing. Here,
      these studies were extended to see whether the same effect could be seen when a
      mixture of waste materials from processing of potatoes and corn into potato and
      corn chips were used as sugar sources. Consistent increases in ethanol production
      coincident with VHb expression were seen in shake flasks at both low aeration and
      high aeration conditions. The ethanol increases were due almost entirely to
      increases in the amount of ethanol produced per unit of cell mass. The VHb
      strategy for increasing fermentation to ethanol (and perhaps other valuable
      fermentation products) may be of general use, particularly regarding conversion
      of otherwise discarded materials into valuable commodities. 

PMID- 25766086
TI  - The nuclear medicine therapy care coordination service: a model for radiologist
      driven patient-centered care.
AB  - We developed a longitudinal care coordination service to proactively deliver high
      quality and family-centered care in patients receiving radioiodine therapy for
      thyroid cancer. In an iterative, multidisciplinary team manner, a pretherapy
      consultation service, which included scripted interactions, documentation, and
      checklists for quality control, evolved over time into a robust patient-centered
      longitudinal care coordination nuclear medicine service. Radiation safety
      precautions, the rationale for therapy, and management of patient expectations
      were addressed through the initial consultation, and discharge and posttreatment
      care were managed during subsequent follow-up. The patient-physician relationship
      created during longitudinal nuclear medicine therapy care is one tool to help
      counteract the growing commoditization of radiology. This article describes the
      process that the nuclear medicine specialists in our department established to
      enhance radiologist value by providing both exceptional thyroid cancer treatment
      and continuity of care.

PMID- 25766087
TI  - The Cognitive Assessment scale for Stroke Patients (CASP) vs. MMSE and MoCA in
      non-aphasic hemispheric stroke patients.
AB  - INTRODUCTION: CASP specifically assesses post-stroke cognitive impairments. Its
      items are visual and as such can be administered to patients with severe
      expressive aphasia. We have previously shown that the CASP was more suitable than
      the Mini Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA)
      in aphasic patients. Our objective was to compare the above scales in non-aphasic
      stroke patients, and assess to what extent the solely visual items of the CASP
      were problematic in cases of neurovisual impairments. METHODS: Fifty non-aphasic
      patients admitted to Physical Medicine and Rehabilitation (PM&R) units after a
      recent left- or right-hemisphere stroke were evaluated with the CASP, MMSE and
      MoCA. We compared these three scales in terms of feasibility, concordance, and
      influence of neurovisual impairments on the total score. RESULTS: Twenty-nine men
      and 21 women were included (mean age 63 +/- 14). For three patients, the MoCa was
      impossible to administer. It took significantly less time to administer the CASP
      (10 +/- 5 min) than the MoCA (11 +/- 5 min, P=0.02), yet it still took more time
      than MMSE administration (7 +/- 3 min, P<10(-6)). Neurovisual impairments
      affected equally the total scores of the three tests. Concordance between these
      scores was poor and only the CASP could specifically assess unilateral spatial
      neglect. CONCLUSION: The sole visual format of the CASP scale seems suitable for
      administration in post-stroke patients.

PMID- 25766088
TI  - What are the perspectives for ventilated tetraplegics? A French retrospective
      study of 108 patients with cervical spinal cord injury.
AB  - OBJECTIVE: Tetraplegic patients are often difficult to manage in intensive care
      units (ICU). The aim of our study was to calculate the incidence of patients in
      ICU with cervical spinal cord injury with special focus on tetraplegic patients
      on ventilation support and their future perspectives. MATERIALS AND METHODS: This
      retrospective study included patients with cervical spinal cord injury in Upper
      Normandy, between 2002 and 2012. Data analyzed included age, sex, past medical
      history, date of onset of quadriplegia, level of neurological involvement, AIS
      grade, and ventilatory status. RESULTS: One hundred and eight patients were
      included (49.0 +/- 21.1 years). The most common etiology was fall (50 patients
      [46.3%]). Incidence was calculated at 12.7 per one million inhabitants.
      Tracheotomy was performed in 40.7% of patients. Long-term mechanical ventilation
      was required for 6.5%. At the end of the study, 9 patients (9.6%) were
      permanently hospitalized, 61 patients (64.9%) had returned home but none of the
      four ventilated patients had been discharged. CONCLUSION: The conclusion of this
      work is that the future of highly tetraplegic patients is compromised, especially
      for those who remain reliant on mechanical ventilation.

PMID- 25766089
TI  - Absence of Microsatellite Instability In Soft Tissue Sarcomas.
AB  - OBJECTIVE: Here, we analyze a series of soft tissue sarcomas (STS), which are a
      heterogeneous group of mesenchymal neoplasms, for the presence and frequency of
      microsatellite instability (MSI). MSI has been proposed to be clinically relevant
      for colorectal cancer, yet on STS its role is not consensual, partly due to the
      limited number of cases analyzed and methodology issues. METHODS: The detailed
      evaluation of MSI in tumor samples from 71 STS patients was performed by
      pentaplex PCR of the MSI markers NR-27, NR-21, NR-24, BAT-25, and BAT-26,
      followed by capillary electrophoresis. The expression of DNA mismatch repair
      (MMR) proteins (MLH1, MSH2, MSH6, and PMS2) was also evaluated in suspected MSI
      positive cases by immunohistochemistry. RESULTS: The MSI analysis showed
      instability of one MSI marker in a total of 3 cases (4.2%). However, MMR protein
      expression was not affected, demonstrating that all cases were microsatellite
      stable. CONCLUSION: Our results suggest that MSI does not play a role in STS
      tumorigenesis. (c) 2015 S. Karger AG, Basel.

PMID- 25766090
TI  - Systemic responses following brain injuries and inflammatory process activation
      induced by a neurotoxin of Androctonus scorpion venom.
AB  - OBJECTIVE: Kaliotoxin 2 (KTX2), a neurotoxin isolated from Androctonus australis
      hector scorpion venom, presents a high affinity with the voltage-gated potassium
      channels. The targets of KTX2 in the brain and its toxic effects on the cerebral
      cortex have been extensively studied; however, its deleterious systemic effects
      on other organ systems have not yet been investigated. Inflammatory response
      induced by KTX2 is supported by cytokine release which could provoke multiple
      organ dysfunction and diverse biological disorders in mammals. The possibility
      that inflammatory response and brain injuries induced by KTX2 may lead to
      functional disturbances, e.g. in the pancreas and the liver, were investigated.
      The contribution of IL-6 and TNF-alpha to the modulation of pathophysiological
      effects induced by KTX2 was also tested. METHODS: NMRI mice were injected by the
      intracerebroventricular route with a sublethal dose of KTX2 or saline solution.
      Inflammatory response and oxidative stress were assessed in sera and tissue
      homogenates. Biomarkers of pancreatic and hepatic functions and the correlation
      with tissue damage in the brain, liver and pancreas were also analyzed. RESULTS:
      The obtained results revealed that KTX2 injection induced an inflammatory process
      activation and imbalanced redox status. It also induced severe alterations in
      cerebral cortex, hepatic and pancreatic tissues associated with a significant
      increase in pancreatic and hepatic pathological biomarkers. Cytokine antagonists
      injected 30 min prior to KTX2 led to a significant reduction of all disturbances
      induced by KTX2. CONCLUSION: In addition to its significant toxicity on the
      central nervous system, KTX2 can also affect pancreatic and hepatic functions,
      probably by an indirect mechanism involving activation of the inflammatory
      response with release of IL-6 and TNF-alpha.

PMID- 25766091
TI  - Heteronuclear 3 d/Dy(III) coordination clusters as catalysts in a domino
      reaction.
AB  - Three isoskeletal tetranuclear coordination clusters with general formula [M(II)
      2 Dy(III) 2 L4 (EtOH)6 ](ClO4 )2 ?2 EtOH, (M=Co, 1; M=Ni, 2) and [Ni(II) 2
      Dy(III) 2 L4 Cl2 (CH3 CN)2 ]?2 CH3 CN (3), have been synthesized and
      characterized. These air-stable compounds, and in particular 3, display efficient
      homogeneous catalytic behavior in the room-temperature synthesis of trans-4,5
      diaminocyclopent-2-enones from 2-furaldehyde and primary or secondary amines
      under a non-inert atmosphere. 

PMID- 25766092
TI  - E-learning in advanced life support--an evaluation by the Resuscitation Council
      (UK).
AB  - AIM: To descriptively analyse the outcomes following the national roll out of an
      e-Learning advanced life support course (e-ALS) compared to a conventional 2-day
      ALS course (c-ALS). METHOD: Between 1st January 2013 and 30th June 2014, 27,170
      candidates attended one of the 1350 Resuscitation Council (UK) ALS courses across
      the UK. 18,952 candidates were enrolled on a c-ALS course and 8218 on an e-ALS
      course. Candidates participating in the e-ALS course completed 6-8h of online e
      Learning prior to attending the 1 day modified face-to-face course. Candidates
      participating in the c-ALS course undertook the Resuscitation Council (UK) 2-day
      face-to-face course. All candidates were assessed by a pre- and post-course MCQ
      and a practical cardiac arrest simulation (CAS-test). Demographic data were
      collected in addition to assessment outcomes. RESULTS: Candidates on the e-ALS
      course had higher scores on the pre-course MCQ (83.7%, SD 7.3) compared to those
      on the c-ALS course (81.3%, SD 8.2, P<0.001). Similarly, they had slightly higher
      scores on the post-course MCQ (e-ALS 87.9%, SD 6.4 vs. c-ALS 87.4%, SD 6.5;
      P<0.001). The first attempt CAS-test pass rate on the e-ALS course was higher
      than the pass rate on the c-ALS course (84.6% vs. 83.6%; P=0.035). The overall
      pass rate was 96.6% on both the e-ALS and c-ALS courses (P=0.776). CONCLUSION:
      The e-ALS course demonstrates equivalence to traditional face-to-face learning in
      equipping candidates with ALS skills when compared to the c-ALS course. Value is
      added when considering benefits such as increased candidate autonomy, cost
      effectiveness, decreased instructor burden and improved standardisation of course
      material. Further dissemination of the e-ALS course should be encouraged.

PMID- 25766093
TI  - Cardiac arrest diagnostic accuracy of 9-1-1 dispatchers: a prospective multi
      center study.
AB  - INTRODUCTION: We sought to determine the ability of 9-1-1 dispatchers to
      accurately determine the presence of out-of-hospital cardiac arrest (OOHCA) over
      the telephone, and to determine the frequency with which CPR instructions are
      initiated and chest compressions delivered in patients not in cardiac arrest.
      METHODS: We conducted a multi-center, prospective cohort study of adult OOHCA
      patients not witnessed by EMS for which resuscitation was attempted. Dispatchers
      were not health care professionals and received 6 weeks of training followed by a
      6-month preceptorship. We reviewed 9-1-1 call digital recordings for all
      unconscious patients for which the possibility of cardiac arrest was considered
      using a piloted standardized data collection sheet. RESULTS: We reviewed 2260
      recordings occurring between January 2008 and October 2009. Among those, 1536
      were confirmed OOHCA, and 724 were not. Among the 1536 confirmed OOHCA cases,
      1012 were recognized by dispatchers and 524 were not. Among the 724 cases not in
      cardiac arrest, dispatchers suspected cardiac arrest was present in 490 and
      absent in 234. OOHCA diagnostic accuracy characteristics were: sensitivity 65.9%
      (95% CI 63.5-68.2%), specificity 32.3% (95% CI 29.0-35.9%), PPV 67.4%, and NPV
      30.9%. Dispatchers believed that OOHCA was present in 490/2260 (21.7%) cases when
      it was not, resulting in 54/490 (11.0%) patients inappropriately receiving chest
      compressions, or 54/2260 (2.4%) of the whole cohort. CONCLUSIONS: Dispatchers had
      a fair sensitivity and modest specificity for the recognition of OOHCA. We found
      a very small number of patients receiving CPR when not in cardiac arrest,
      supporting the current use of dispatch-assisted CPR instructions.

PMID- 25766094
TI  - Mechanical chest compressions improved aspects of CPR in the LINC trial.
AB  - AIM: We studied resuscitation process metrics in patients with out-of-hospital
      cardiac arrest enrolled in a randomized trial comparing one protocol designed to
      best use a mechanical CPR device, with another based on the 2005 European
      Resuscitation Council guidelines for manual CPR. METHODS: We analyzed clinical
      data, ECG signals, and transthoracic impedance signals for a subset of the
      patients in the LUCAS in Cardiac Arrest (LINC) trial, including 124 patients
      randomized to mechanical and 82 to manual CPR. Chest compression fraction (CCF)
      was defined as the fraction of time during cardiac arrest that chest compressions
      were administered. RESULTS: Patients in the mechanical CPR group had a higher CCF
      than those in the manual CPR group [0.84 (0.78, 0.91) vs. 0.79 (0.70, 0.86), p <
      0.001]. The median duration of their pauses for defibrillation was also shorter
      [0 s (0, 6.0) vs. 10.0 s (7.0, 14.3), p < 0.001]. Compressions were interrupted
      for a median of 36.0 s to apply the compression device. There was no difference
      between groups in duration of the longest pause in compressions [32.5s vs. 26.0
      s, p = 0.24], number of compressions received per minute [86.5 vs. 88.3, p =
      0.47], defibrillation success rate [73.2% vs. 81.0%, p = 0.15], or refibrillation
      rate [74% vs. 77%, p = 0.79]. CONCLUSIONS: A protocol using mechanical chest
      compression devices reduced interruptions in chest compressions, and enabled
      defibrillation during ongoing compressions, without adversely affecting other
      resuscitation process metrics. Future emphasis on optimizing device deployment
      may be beneficial.

PMID- 25766097
TI  - A review of phalangeal neck fractures in children.
AB  - Phalangeal neck fractures are uncommon and are almost exclusively seen in
      children. Most paediatric hand fractures are treated conservatively and an
      excellent outcome is expected in almost all cases. Paediatric phalangeal neck
      fractures are different mainly because they are unstable and have a high risk of
      complications. Even minimally displaced phalangeal neck fractures are known to be
      unstable following reduction and hence k-wire fixation is required. Furthermore,
      complications such as persistent deformity, nonunion, and avascular necrosis are
      commonly seen following management of phalangeal neck fractures; such
      complications are extremely rare in other paediatric hand fractures. The current
      paper aims to review the diagnosis, classification, management and complications
      of these fractures in children. The paper also aims to introduce an extended
      classification of phalangeal neck fractures and to explain the clinical relevance
      of the extended classification. 

PMID- 25766096
TI  - Collider bias in trauma comparative effectiveness research: the stratification
      blues for systematic reviews.
AB  - BACKGROUND: Collider bias, or stratifying data by a covariate consequence rather
      than cause (confounder) of treatment and outcome, plagues randomised and
      observational trauma research. Of the seven trials of prehospital hypertonic
      saline in dextran (HSD) that have been evaluated in systematic reviews, none
      found an overall between-group difference in survival, but four reported
      significant subgroup effects. We hypothesised that an avoidable type of collider
      bias often introduced inadvertently into trauma comparative effectiveness
      research could explain the incongruous findings. METHODS: The two most recent HSD
      trials, a single-site pilot and a multi-site pivotal study, provided data for a
      secondary analysis to more closely examine the potential for collider bias. The
      two trials had followed the a priori statistical analysis plan to subgroup
      patients by a post-randomisation covariate and well-established surrogate for
      bleeding severity, massive transfusion (MT), >= 10 unit of red blood cells within
      24h of admission. Despite favourable HSD effects in the MT subgroup, opposite
      effects in the non-transfused subgroup halted the pivotal trial early. In
      addition to analyzing the data from the two trials, we constructed causal
      diagrams and performed a meta-analysis of the results from all seven trials to
      assess the extent to which collider bias could explain null overall effects with
      subgroup heterogeneity. RESULTS: As in previous trials, HSD induced significantly
      greater increases in systolic blood pressure (SBP) from prehospital to admission
      than control crystalloid (p=0.003). Proportionately more HSD than control
      decedents accrued in the non-transfused subgroup, but with paradoxically longer
      survival. Despite different study populations and a span of over 20 years across
      the seven trials, the reported mortality effects were consistently null, summary
      RR=0.99 (p=0.864, homogeneity p=0.709). CONCLUSIONS: HSD delayed blood
      transfusion by modifying standard triggers like SBP with no detectable effect on
      survival. The reported heterogeneous HSD effects in subgroups can be explained by
      collider bias that trauma researchers can avoid by improved covariate selection
      and data capture strategies.

PMID- 25766095
TI  - Restoration of mitochondria function as a target for cancer therapy.
AB  - Defective oxidative phosphorylation has a crucial role in the attenuation of
      mitochondrial function, which confers therapy resistance in cancer. Various
      factors, including endogenous heat shock proteins (HSPs) and exogenous agents
      such as dichloroacetate, restore respiratory and other physiological functions of
      mitochondria in cancer cells. Functional mitochondria might ultimately lead to
      the restoration of apoptosis in cancer cells that are refractory to current
      anticancer agents. Here, we summarize the key reasons contributing to
      mitochondria dysfunction in cancer cells and how restoration of mitochondrial
      function could be exploited for cancer therapeutics. 

PMID- 25766098
TI  - De novo assembly and characterization of transcriptomes of early-stage fruit from
      two genotypes of Annona squamosa L. with contrast in seed number.
AB  - BACKGROUND: Annona squamosa L., a popular fruit tree, is the most widely
      cultivated species of the genus Annona. The lack of transcriptomic and genomic
      information limits the scope of genome investigations in this important shrub. It
      bears aggregate fruits with numerous seeds. A few rare accessions with very few
      seeds have been reported for Annona. A massive pyrosequencing (Roche, 454 GS
      FLX+) of transcriptome from early stages of fruit development (0, 4, 8 and 12
      days after pollination) was performed to produce expression datasets in two
      genotypes, Sitaphal and NMK-1, that show a contrast in the number of seeds set in
      fruits. The data reported here is the first source of genome-wide differential
      transcriptome sequence in two genotypes of A. squamosa, and identifies several
      candidate genes related to seed development. RESULTS: Approximately 1.9 million
      high-quality clean reads were obtained in the cDNA library from the developing
      fruits of both the genotypes, with an average length of about 568 bp. Quality
      reads were assembled de novo into 2074 to 11004 contigs in the developing fruit
      samples at different stages of development. The contig sequence data of all the
      four stages of each genotype were combined into larger units resulting into 14921
      (Sitaphal) and 14178 (NMK-1) unigenes, with a mean size of more than 1 Kb.
      Assembled unigenes were functionally annotated by querying against the protein
      sequences of five different public databases (NCBI non redundant, Prunus persica,
      Vitis vinifera, Fragaria vesca, and Amborella trichopoda), with an E-value cut
      off of 10(-5). A total of 4588 (Sitaphal) and 2502 (NMK-1) unigenes did not match
      any known protein in the NR database. These sequences could be genes specific to
      Annona sp. or belong to untranslated regions. Several of the unigenes
      representing pathways related to primary and secondary metabolism, and seed and
      fruit development expressed at a higher level in Sitaphal, the densely seeded
      cultivar in comparison to the poorly seeded NMK-1. A total of 2629 (Sitaphal) and
      3445 (NMK-1) Simple Sequence Repeat (SSR) motifs were identified respectively in
      the two genotypes. These could be potential candidates for transcript based
      microsatellite analysis in A. squamosa. CONCLUSION: The present work provides
      early-stage fruit specific transcriptome sequence resource for A. squamosa. This
      repository will serve as a useful resource for investigating the molecular
      mechanisms of fruit development, and improvement of fruit related traits in A.
      squamosa and related species.

PMID- 25766099
TI  - Small T-antigen of the TS-associated polyomavirus activates factors implicated in
      the MAPK pathway.

PMID- 25766100
TI  - Interrelations between pain and alcohol: An integrative review.
AB  - Pain and alcohol use are both highly prevalent in the general population, and
      pain-alcohol interrelations are of increasing empirical interest. Previous
      research has identified associations between pain and alcohol dependence, and the
      current review provides novel contributions to this emerging domain by
      incorporating studies that have tested relations between pain and low-to-moderate
      alcohol consumption, and by identifying potential psychosocial mechanisms of
      action. Specifically, we sought to integrate evidence of pain-alcohol relations
      derived from two directions of empirical inquiry (i.e., effects of alcohol on
      pain and effects of pain on alcohol use) across psychological, social, and
      biological literatures. We observed converging evidence that associations between
      alcohol consumption and pain may be curvilinear in nature. Whereas moderate
      alcohol use was observed to be associated with positive pain-related outcomes
      (e.g., greater quality of life), excessive drinking and alcohol use disorder
      appear to be associated with deleterious pain-related outcomes (e.g., greater
      pain severity). We also observed evidence that alcohol administration confers
      acute pain-inhibitory effects, and that situational pain may motivate alcohol
      consumption (e.g., drinking for pain-coping). Future research can inform
      theoretical and clinical applications through examination of temporal relations
      between pain and alcohol consumption, tests of hypothesized mechanisms, and the
      development of novel interventions.

PMID- 25766104
TI  - 1- and 2-year-olds' expectations about third-party communicative actions.
AB  - Infants expect people to direct actions toward objects, and they respond to
      actions directed to themselves, but do they have expectations about actions
      directed to third parties? In two experiments, we used eye tracking to
      investigate 1- and 2-year-olds' expectations about communicative actions
      addressed to a third party. Experiment 1 presented infants with videos where an
      adult (the Emitter) either uttered a sentence or produced non-speech sounds. The
      Emitter was either face-to-face with another adult (the Recipient) or the two
      were back-to-back. The Recipient did not respond to any of the sounds. We found
      that 2-, but not 1-year-olds looked quicker and longer at the Recipient following
      speech than non-speech, suggesting that they expected her to respond to speech.
      These effects were specific to the face-to-face context. Experiment 2 presented 1
      year-olds with similar face-to-face exchanges but modified to engage infants and
      minimize task demands. The infants looked quicker to the Recipient following
      speech than non-speech, suggesting that they expected a response to speech. The
      study suggests that by 1 year of age infants expect communicative actions to be
      directed at a third-party listener. 

PMID- 25766103
TI  - Maternal prenatal psychological distress and temperament in 1-4 month old infants
      - A study in a non-western population.
AB  - In this longitudinal study, conducted in women attending antenatal visits at the
      obstetrics and gynecology clinic of a general hospital in Bangalore, India, we
      aimed to assess the relationship between prenatal distress in mothers, and
      maternal report of infant temperament at four months. 100 mothers with normal
      full term deliveries completed the General Health Questionnaire-28 item version
      (GHQ) in the third trimester and postnatally. Salivary cortisol and temperament
      (using the Early Infancy Temperament Questionnaire - EITQ) were assessed in their
      infants aged 1-4 months. In this study, maternal prenatal psychological distress
      was not significantly associated with maternal report of difficult temperament in
      infants. Infants of mothers who were a negative screen for psychological distress
      (GHQ<7), n=85 had higher scores on the adaptability and approach dimensions of
      temperament. Infant salivary cortisol was significantly higher in infants with
      higher intensity scores. These results introduce the possibility of cultural
      differences in the relationship between prenatal distress in the mother and
      infant temperament. These could be factors linked to child rearing practices or
      to the measures employed to study infant temperament. These findings derive from
      a small sample with few mothers with psychological distress, and need replication
      in a larger sample. 

PMID- 25766105
TI  - Colonoscopy-assisted laparoscopic resection of an obstructing 'giant' lipoma of
      the transverse colon.

PMID- 25766106
TI  - Effects of simulated oxidation on the in vitro wear and mechanical properties of
      irradiated and melted highly crosslinked UHMWPE.
AB  - Radiation crosslinked ultrahigh molecular weight polyethylene (UHMWPE) have
      reduced the wear rate of the bearing surface in total joint arthroplasty and the
      incidence of peri-prosthetic bone loss due to wear particles. The oxidation
      potential afforded to the material by the trapped residual free radicals after
      irradiation was addressed in first generation crosslinked UHMWPEs by using
      thermal treatments such as annealing or melting after irradiation.
      Postirradiation melted crosslinked UHMWPE did not contain detectable free
      radicals at the time of implantation and was expected to be resistant against
      oxidation for the lifetime of the implants. Recent analyses of long-term
      retrievals showed it was possible for irradiated and melted UHMWPEs to oxidize in
      vivo but studies on the effects of oxidation on these materials have been
      limited. In this study, we determined the effects of in vitro aging on the wear
      and mechanical properties of irradiated and melted UHMWPE as a function of
      radiation dose and found that even small amount of oxidation (oxidation index of
      0.1) can have detrimental effects on its mechanical properties. There was a
      gradual increase in the wear rate below an oxidation index of 1 and a drastic
      increase thereafter. Therefore, it was shown in a simulated environment that
      oxidation can have detrimental effects to the clinically relevant properties of
      irradiated and melted UHMWPEs.

PMID- 25766107
TI  - Sirtuins in vascular diseases: Emerging roles and therapeutic potential.
AB  - Silent information regulator-2 (Sir-2) proteins, or sirtuins, are a highly
      conserved protein family of histone deacetylases that promote longevity by
      mediating many of the beneficial effects of calorie restriction which extends
      life span and reduces the incidence of cancer, cardiovascular disease (CVD), and
      diabetes. Here, we review the role of sirtuins (SIRT1-7) in vascular homeostasis
      and diseases by providing an update on the latest knowledge about their roles in
      endothelial damage and vascular repair mechanisms. Among all sirtuins, in the
      light of the numerous functions reported on SIRT1 in the vascular system, herein
      we discuss its roles not only in the control of endothelial cells (EC)
      functionality but also in other cell types beyond EC, including endothelial
      progenitor cells (EPC), smooth muscle cells (SMC), and immune cells. Furthermore,
      we also provide an update on the growing field of compounds under clinical
      evaluation for the modulation of SIRT1 which, at the state of the art, represents
      the most promising target for the development of novel drugs against CVD,
      especially when concomitant with type 2 diabetes. 

PMID- 25766108
TI  - The flavo-oxidase QSOX1 supports vascular smooth muscle cell migration and
      proliferation: Evidence for a role in neointima growth.
AB  - Quiescin sulfhydryl oxidase 1 (QSOX1) is a flavoenzyme largely present in the
      extracellular milieu whose physiological functions and substrates are not known.
      QSOX1 has been implicated in the regulation of tumor cell survival, proliferation
      and migration, in addition to extracellular matrix (ECM) remodeling. However,
      data regarding other pathophysiological conditions are still lacking. Arterial
      injury by balloon catheter is an established model of post-angioplasty
      restenosis. This technique induces neointima formation due to migration and
      proliferation of vascular smooth muscle cells (VSMC), followed by ECM synthesis
      and remodeling. Here, we show that QSOX1 knockdown inhibited VSMC migration and
      proliferation in vitro. In contrast, QSOX1 overexpression stimulated these
      processes. While migration could be induced by the incubation of cells with the
      active recombinant QSOX1, proliferation was induced by addition of the active and
      also of an inactive mutant QSOX1 protein. The proliferation induced by both
      recombinants was independent of intracellular hydrogen peroxide and dependent of
      the MEK/ERK pathway. To recapitulate in vivo VSMC pathophysiology, balloon
      induced arterial injury was performed. The expression of QSOX1 in the neointimal
      layer of balloon-injured rat carotids was high and peaked at 14 days post-injury.
      In vivo QSOX1 knockdown led to a significant decrease in PCNA expression at day
      14 post-injury and a decreased intima/media area ratio at day 21 post-injury,
      compared with scrambled siRNA transfection. In summary, our findings demonstrate
      that QSOX1 induces VSMC migration and proliferation in vitro and contributes to
      neointima thickening in balloon-injured rat carotids.

PMID- 25766109
TI  - Hymenobacter wooponensis sp. nov., isolated from wetland freshwater.
AB  - A non-motile and rod-shaped bacterium, designated strain WM78T, was isolated from
      freshwater collected from the Woopo wetland (Republic of Korea). Cells were Gram
      stain-negative, aerobic, catalase-positive and oxidase-negative. The major fatty
      acids were iso-C15:0, anteiso-C15:0, C16:1omega7c and/or C16:1omega6c and iso
      C17:1 I and/or anteiso-C17:1 B. The strain contained MK-7 as the major isoprenoid
      quinone, phosphatidylethanolamine as the major polar lipid and sym-homospermidine
      as the major polyamine. The genomic DNA G+C content was 62 mol%. A phylogenetic
      tree based on 16S rRNA gene sequences showed that strain WM78T forms evolutionary
      lineage within the radiation comprising members of the genus Hymenobacter with
      Hymenobacter gelipurpurascens Txg1T (97.7 % sequence similarity) as its nearest
      neighbour. A number of phenotypic characteristics distinguished strain WM78T from
      related members of the genus Hymenobacter. The evidence presented in this study
      support the designation of strain WM78T as a representative of a novel species in
      the genus Hymenobacter for which the name Hymenbactor wooponensis sp. nov. is
      proposed. The type strain is WM78T ( = KCTC 32528T = JCM 19491T).

PMID- 25766110
TI  - Amphritea spongicola sp. nov., isolated from a marine sponge, and emended
      description of the genus Amphritea.
AB  - A Gram-stain-negative, rod-shaped (1.2-2.1 MUm * 0.8-0.9 MUm), flagellated and
      motile marine bacterium, designated MEBiC05461T, was isolated from a marine
      sponge inhabiting Micronesia. Strain MEBiC05461T was oxidase-negative and
      catalase-positive. Growth was observed at 8.0-35.6  degrees C (optimum 30.0 
      degrees C), at pH 5.0-9.0 (optimum pH 7.0) and with 1.5-6.0 % (w/v, optimum 2.0
      2.5 %) NaCl. 16S rRNA gene sequence analysis revealed that strain MEBiC05461T
      showed high similarity to members of the genus Amphritea (96.4-96.6 %). The
      predominant cellular fatty acids were C16:0 (23.9 %), summed feature 3
      (C16:1omega7c and/or C16:1omega6c; 39.7 %) and summed feature 8 (C18:1omega7c
      and/or C18:1omega6c; 22.0 %). The DNA G+C content was 48.5 mol%. The major
      respiratory quinone was Q-8.Phosphatidylethanolamine, phosphatidylglycerol, one
      unidentified glycolipid, one unidentified aminolipid, one unidentified
      glycophospholipid and two unidentified lipids were detected as the major polar
      lipids. On the basis of the data from this polyphasic taxonomic study, strain
      MEBiC05461T should be classified as a representative of a novel species in the
      genus Amphritea, and the name proposed is Amphritea spongicola sp. nov. The type
      strain is MEBiC05461T ( = KCCM 42943T = JCM 16668T). Emendations of the genus
      Amphritea and species Amphritea atlanticaGartner et al. 2008 and Amphritea
      balenaeMiyazaki et al. 2008 are were also given.

PMID- 25766112
TI  - The Interleukin-13 Receptor-alpha1 Chain Is Essential for Induction of the
      Alternative Macrophage Activation Pathway by IL-13 but Not IL-4.
AB  - Macrophages coexpress both the interleukin (IL)-2Rgamma chain (gamma(c)) and IL
      13Ralpha1. These receptor chains can heterodimerize with IL-4Ralpha to form type
      I or type II IL-4 receptor complexes, respectively. We used macrophages derived
      from Il2rg and Il13ra1 knockout (KO) mice to evaluate the requirements for these
      receptor chains for induction of the alternative macrophage activation (AMA)
      pathway by IL-4 and IL-13. Absence of gamma(c) significantly decreased activation
      of STAT6 by IL-4 but not IL-13. However, although activation of STAT6 by IL-4 was
      markedly reduced in gamma(c) KO macrophages, it was not abolished, indicating
      that IL-4 can still signal through type II IL-4 receptors via the IL-13Ralpha1
      chain. IL-13 failed to activate STAT6 in macrophages derived from Il13ra1 KO
      mice; however, these cells remained fully responsive to IL-4. The inability of IL
      13 but not IL-4 to signal in Il13ra1(-/-) macrophages correlated with the
      inability of IL-13 but not IL-4 to induce expression of genes such as Arg1,
      Retnla and Ccl11 that are characteristically expressed by alternatively activated
      macrophages. In addition, IL-13 but not IL-4 failed to induce membrane fusion and
      giant cell formation by Il13ra1 KO macrophages. These findings demonstrate that
      the IL-13Ralpha1 chain is essential for induction of the AMA pathway by IL-13 but
      not IL-4.

PMID- 25766113
TI  - Catholuminescence properties of rare earth doped CaSnO3 phosphor.
AB  - The present study describes cathodoluminescence (CL) properties of CaSnO3
      phosphors doped with Eu(3+), Tb(3+) and Dy(3+) synthesized by a solid-state
      method. X-ray diffraction (XRD) patterns confirm that CaSnO3 sintered at 1200
      degrees C exhibits orthorhombic structure. The evidence and rationale for two
      strong broad emission bands appeared at 360 and 780nm for undoped CaSnO3 are
      presented. The CL measurements exhibit that the 4f-4f emissions from (5)D4->(7)F6
      (490nm), (5)D4 ->(7)F5 (544nm), (5)D4 ->(7)F4 (586nm) and (5)D4 ->(7)F3 (622nm),
      assigned to possible transitions of Tb(3+) ions are seen. The strongest one,
      observed at 544nm, due to its probability of both magnetic and electric
      transitions make the sample emission green. Emissions at 480, 574, 662 and 755nm
      were detected for the CaSnO3:Dy(3+) and attributed to the transitions from the
      (4)F9/2 to various energy levels (6)H15/2, (6)H13/2, (6)H11/2 and
      (6)H9/2+(6)F11/2 of Dy(3+), respectively. CL spectra of Eu doped CaSnO3 reveal
      that there is a strong emission peak appeared at 615nm due to the electric dipole
      transition (5)D0->(7)F2 (red). Finally, our results show that the rare earth
      doped CaSnO3 have remarkable potential for applications as optical materials
      since it exhibits efficient and sharp emission due to rare earth ions. 

PMID- 25766114
TI  - Radiotracer investigation in an industrial-scale oxidizer.
AB  - A radiotracer investigation was carried out in an industrial-scale oxidizer. The
      main objectives of the investigation were to measure residence time distribution
      (RTD) of organic process fluid, determine the mean residence time (MRT) and
      investigate the degree of axial mixing. Bromine-82 as p-dibromo biphenyl was used
      as a radiotracer for measuring RTD of the organic process fluid. The MRT of the
      fluid in the oxidizer was determined to be 390min. An ideal stirred tank model
      with a plug flow reactor in recirculation stream was used to simulate the
      measured RTD data and was found suitable for describing flow in the system. Based
      on the model simulation the mean residence times in oxidizer and recycle stream
      were estimated. The results of the investigation showed that the oxidizer behaved
      as a well-mixed reactor whereas the recycle stream behaved as a plug flow
      reactor. 

PMID- 25766115
TI  - Simulation of metal-organic framework self-assembly.
AB  - Spontaneous growth of metal-organic frameworks (MOFs) composed of metal ions and
      4,4'-bipyridine ligands was successfully demonstrated by molecular dynamics
      simulations, starting from a random initial placement of the metals and the
      ligands. The effect of the metal-ligand binding strength upon the MOF self
      assembly was investigated. We found that the metal-ligand binding strength should
      be within a window around the optimum values for the regular MOF growth. 

PMID- 25766116
TI  - Morphology of human sweat ducts observed by optical coherence tomography and
      their frequency of resonance in the terahertz frequency region.
AB  - It is crucial to understand the various biological effects induced by terahertz
      (THz) electromagnetic waves with the rapid development of electronic and photonic
      devices operating in the THz frequency region. The presence of sweat glands plays
      an important role in THz wave interactions with human skin. We investigated the
      morphological features of sweat ducts using optical coherence tomography (OCT) to
      further understand such phenomena. We observed remarkable features of the ducts,
      such as their clear helical structure. The intersubject and intrasubject
      variations in the diameter of sweat ducts were considerably smaller than the
      variations in other structural parameters, such as length and number of turns.
      Based on the sweat duct dimensions and THz dielectric properties of skin measured
      using terahertz time-domain spectroscopy (THz-TDS), we calculated the resonating
      frequency of the sweat duct under the assumption of it functioning as a helical
      antenna. Here, we show that the resonance frequency in the axial mode of
      operation lies in the THz wave region with a centre frequency of 0.44 +/- 0.07
      THz. We expect that these findings will further our understanding of the various
      health consequences of the interaction of THz waves with human beings.

PMID- 25766117
TI  - Virus genome dynamics under different propagation pressures: reconstruction of
      whole genome haplotypes of West Nile viruses from NGS data.
AB  - BACKGROUND: Extensive focus is placed on the comparative analyses of consensus
      genotypes in the study of West Nile virus (WNV) emergence. Few studies account
      for genetic change in the underlying WNV quasispecies population variants. These
      variants are not discernable in the consensus genome at the time of emergence,
      and the maintenance of mutation-selection equilibria of population variants is
      greatly underestimated. The emergence of lineage 1 WNV strains has been studied
      extensively, but recent epidemics caused by lineage 2 WNV strains in Hungary,
      Austria, Greece and Italy emphasizes the increasing importance of this lineage to
      public health. In this study we explored the quasispecies dynamics of minority
      variants that contribute to cell-tropism and host determination, i.e. the ability
      to infect different cell types or cells from different species from Next
      Generation Sequencing (NGS) data of a historic lineage 2 WNV strain. RESULTS:
      Minority variants contributing to host cell membrane association persist in the
      viral population without contributing to the genetic change in the consensus
      genome. Minority variants are shown to maintain a stable mutation-selection
      equilibrium under positive selection, particularly in the capsid gene region.
      CONCLUSIONS: This study is the first to infer positive selection and the
      persistence of WNV haplotype variants that contribute to viral fitness without
      accompanying genetic change in the consensus genotype, documented solely from NGS
      sequence data. The approach used in this study streamlines the experimental
      design seeking viral minority variants accurately from NGS data whilst minimizing
      the influence of associated sequence error.

PMID- 25766118
TI  - A Markov model to evaluate cost-effectiveness of antiangiogenesis therapy using
      bevacizumab in advanced cervical cancer.
AB  - OBJECTIVE: To evaluate the cost-effectiveness of bevacizumab in
      recurrent/persistent and metastatic cervical cancer using recently reported
      updated survival and toxicology data. METHODS: A Markov decision tree based on
      the Gynecologic Oncology Group 240 randomized trial was created. The 2013
      MediCare Services Drug Payment Table and Physician Fee Schedule provided costs.
      In the 5-year model subjects transitioned through the following states: response,
      progression, minor complications, severe complications, and death. Patients
      experiencing a health utility per month according to treatment effectiveness were
      calculated. Because cervical cancer survival is measured in months rather than
      years, results were reported in both quality adjusted cervical cancer life months
      and years (QALmonth, QALY), adjusted from a baseline of having advanced cervical
      cancer during a month. RESULTS: The estimated total cost of therapy with
      bevacizumab is approximately 13.2 times that for chemotherapy alone, adding
      $73,791 per 3.5months (0.29year) of life gained, resulting in an incremental cost
      effectiveness ratio (ICER) of $21.083 per month of added life. The ICER increased
      to $5775 per month of added life and $24,597/QALmonth ($295,164/QALY) due to the
      smaller difference in QALmonths. With 75% bevacizumab cost reduction, the ICER is
      $6737/QALmonth ($80,844/QALY), which translates to $23,580 for the 3.5month
      (0.29year) gain in OS. CONCLUSIONS: Increased costs are primarily related to the
      cost of drug and not the management of bevacizumab-induced complications. Cost
      reductions in bevacizumab result in dramatic declines in the ICER, suggesting
      that cost reconciliation in advanced cervical cancer may be possible through the
      availability of biosimilars, and/or less expensive, equally efficacious anti
      angiogenesis agents.

PMID- 25766119
TI  - A population-based comparison of open versus minimally invasive abdominoperineal
      resection.
AB  - BACKGROUND: Although minimally invasive colorectal surgery increases widely,
      outcomes following its use in complex operations such as the abdominoperineal
      resection (APR) remain indeterminate. METHODS: A review of the Nationwide
      Inpatient Sample (2008 to 2011) of all patients undergoing elective laparoscopic
      or open APR was conducted. Risk-adjusted 30-day outcomes were assessed using
      regression modeling accounting for patient characteristics, comorbidities, and
      surgical procedure. RESULTS: We identified 3,191 admissions meeting inclusion
      criteria (1,019 laparoscopic; 2,172 open). The conversion rate was 5%. Mortality
      was low and similar between groups (.88% vs .83%, P = .91). In-hospital
      complication rates were lower in the laparoscopic group (19% vs 29%, odds ratio
      .59, 95% confidence interval .49 to .71, P < .01), but conversion was associated
      with a higher rate (29% vs 18%, P < .01). Finally, a laparoscopic APR was
      associated with a shorter length of stay (5.3 vs 7.0 days, P < .01). CONCLUSION:
      Laparoscopic APR is associated with improved outcomes and may be the preferred
      approach by surgeons with appropriate skills and experience.

PMID- 25766120
TI  - Flow Cytometry and Electron Microscopy Study of Staphylococcus aureus and
      Escherichia coli Treated with Mdc-Hly.
AB  - In our previous study, a novel hybrid protein combining human lysozyme (Hly) with
      Musca domestica cecropin (Mdc) was successfully constructed. The broad
      antibacterial activity against various foodborne pathogens of Mdc-hly suggests
      its scope as a food preservative. The aim of the present study was to investigate
      the antibacterial mechanism of the recombinant Mdc-hly. The damage induced by Mdc
      hly on Staphylococcus aureus and Escherichia coli was investigated using flow
      cytometry (FC), scanning electron microscopy (SEM), and transmission electron
      microscopy (TEM). The results of FC showed that Mdc-hly causes bacterial membrane
      permeabilization. SEM and TEM studies revealed that Mdc-hly is capable of
      damaging both the membrane and the wall of bacteria, resulting in efflux of
      essential cytoplasmic contents. Both FC and EM revealed that the effects of Mdc
      hly were greater than its parental peptides. Understanding the antibacterial
      mechanism of Mdc-hly is of a great interest in further utilization of its use in
      treatment of food and in clinical environments. 

PMID- 25766121
TI  - Post stroke pain: identification, assessment, and therapy.
AB  - BACKGROUND: Pain is a common complication after stroke and is associated with the
      presence of depression, cognitive dysfunction, and impaired quality of life. It
      remains underdiagnosed and undertreated, despite evidence that effective
      treatment of pain may improve function and quality of life. SUMMARY: We provide
      an overview of the means for clinical assessment and risk factors for the
      development of post-stroke pain, then review the newest available literature
      regarding the commonest post-stroke pain syndromes, including central post-stroke
      pain, complex regional pain syndrome, musculoskeletal pain including shoulder
      subluxation, spasticity-related pain, and post-stroke headache, as well as the
      available epidemiology and current treatment options. Key Messages: In the best
      interests of optimizing quality of life and function after stroke, clinicians
      should be aware of pain as a common complication after stroke, identify those
      patients at highest risk, directly inquire as to the presence and characteristics
      of pain, and should be aware of the options for treatment for the various pain
      syndromes.

PMID- 25766122
TI  - Genome-wide expression profiling and phenotypic evaluation of European maize
      inbreds at seedling stage in response to heat stress.
AB  - BACKGROUND: Climate change will lead in the future to an occurrence of heat waves
      with a higher frequency and duration than observed today, which has the potential
      to cause severe damage to seedlings of temperate maize genotypes. In this study,
      we aimed to (I) assess phenotypic variation for heat tolerance of temperate
      European Flint and Dent maize inbred lines, (II) investigate the transcriptomic
      response of temperate maize to linearly increasing heat levels and, (III)
      identify genes associated with heat tolerance in a set of genotypes with
      contrasting heat tolerance behaviour. RESULTS: Strong phenotypic differences with
      respect to heat tolerance were observed between the examined maize inbred lines
      on a multi-trait level. We identified 607 heat responsive genes as well as 39
      heat tolerance genes. CONCLUSION: Our findings indicate that individual inbred
      lines developed different genetic mechanisms in response to heat stress. We
      applied a novel statistical approach enabling the integration of multiple
      genotypes and stress levels in the analysis of abiotic stress expression studies.

PMID- 25766123
TI  - The direct conversion of sugars into 2,5-furandicarboxylic acid in a triphasic
      system.
AB  - A one-pot conversion of sugars into 2,5-furandicarboxylic acid (FDCA) is
      demonstrated in a triphasic system: tetraethylammonium bromide (TEAB) or water
      methyl isobutyl ketone (MIBK)-water. In this reaction, sugars are first converted
      into 5-hydroxymethylfurfural (HMF) in TEAB or water (Phase I). The HMF in Phase I
      is then extracted to MIBK (Phase II) and transferred to water (Phase III), where
      HMF is converted into FDCA. Phase II plays multiple roles: as a bridge for HMF
      extraction, transportation and purification. Overall FDCA yields of 78 % and 50 %
      are achieved from fructose and glucose respectively. 

PMID- 25766124
TI  - Lung Volume Reduction Coil Treatment: Is There an Indication for Antibiotic
      Prophylaxis?

PMID- 25766125
TI  - Alcohol Use Disorders and Community-Acquired Pneumococcal Pneumonia: Associated
      Mortality, Prolonged Hospital Stay and Increased Hospital Spending.
AB  - INTRODUCTION: The aim of this study was to investigate the impact of alcohol use
      disorders (AUD) on community-acquired pneumococcal pneumonia (CAPP) admissions,
      in terms of in-hospital mortality, prolonged stay and increased hospital
      spending. METHODS: Retrospective observational study of a sample of CAPP patients
      from the minimum basic datasets of 87 Spanish hospitals during 2008-2010.
      Mortality, length of hospital stay and additional spending attributable to AUD
      were calculated after multivariate covariance analysis for variables such as age
      and sex, type of hospital, addictions and comorbidities. RESULTS: Among 16,202
      non-elective admissions for CAPP in patients aged 18-74years, 2,685 had AUD.
      Patients admitted with CAPP and AUD were predominantly men with a higher
      prevalence of tobacco or drug use disorders and higher Charlson comorbidity
      index. Patients with CAPP and AUD had notably higher in-hospital mortality
      (50.8%; CI95%: 44.3-54.3%), prolonged length of stay (2.3days; CI95%: 2.0
      2.7days) and increased costs (1,869.2?; CI95%: 1,498.6-2,239.8?). CONCLUSIONS:
      According to the results of this study, AUD in CAPP patients was associated with
      increased in-hospital mortality, length of hospital stay and hospital spending.

PMID- 25766126
TI  - Association of Three Developmental Lung Anomalies in an Adult.

PMID- 25766127
TI  - Bilateral Oleothorax.

PMID- 25766128
TI  - Correlation between abdominal rectus diastasis width and abdominal muscle
      strength.
AB  - BACKGROUND: Surgery for Abdominal Rectus Diastasis (ARD) is a controversial topic
      and some argue that it is solely an aesthetic problem. Many symptoms in these
      patients are indefinite, and no objective criteria have been established,
      indicating which patients are likely to benefit from surgery. This study
      investigated the correlation between preoperative assessment and intraoperative
      measurement of ARD width, and objective measurements of muscle strength. METHODS:
      57 patients undergoing surgery for ARD underwent preoperative assessment of ARD
      width by clinical measurement and CT scan, and thereafter intraoperative
      measurement. Abdominal muscle strength was investigated using the Biodex System 4
      including flexion, extension and isometric measurements. Correlations were
      calculated by the Spearman test. RESULTS: Intraoperative ARD width between the
      umbilicus and the symphysis correlated strongly with Biodex measurements during
      flexion (p = 0.007, R = -0.35) and isometric work load (p = 0.01, R = -0.34). The
      following measurements showed no correlation: between muscle strength and BMI;
      muscle strength and waistline; or between muscle strength and ARD width above the
      umbilicus, assessed preoperatively at the outpatient clinic, by CT scan, or
      measured intraoperatively. CONCLUSION: There is a strong correlation between
      intraoperatively measured ARD width below the umbilicus and flexion and isometric
      abdominal muscle strength measured with the Biodex System 4.

PMID- 25766129
TI  - BRAF, KIT and NRAS mutations and expression of c-KIT, phosphorylated
      extracellular signal-regulated kinase and phosphorylated AKT in Japanese melanoma
      patients.
AB  - To clarify the status of gene mutation and activation of growth signal in
      melanoma of Japanese patients in vivo, we analyzed the mutation of BRAF exon 15,
      NRAS exon 2, and KIT exons 9, 11, 13, 17 and 18 in melanoma cells obtained by
      laser capture microdissection, and performed direct sequencing in 20 cases of
      acral lentiginous melanoma (ALM) and 17 cases of superficial spreading melanoma
      (SSM). In the study of the mutation of BRAF, pyrosequencing was also done. To
      examine the cell proliferation signaling, immunohistochemistry for phosphorylated
      extracellular signal-regulated kinase (pERK), phosphorylated AKT (phosphorylated
      AKT) and c-KIT was done. The mutation of BRAF p.V600E was detected in 13 cases of
      ALM (65.0%) and 12 cases of SSM (70.6%). No NRAS mutation was found in all cases.
      The mutation in exons 9, 11, and 18 of KIT was detected in nine cases. The
      mutation of BRAF and KIT showed no correlation with clinical stage, lymph node
      metastasis, tumor thickness, ulceration and histology. pERK and pAKT was observed
      in small population of melanoma cells and there was no correlation with gene
      mutation. Our results indicate that the mutations of BRAF and KIT exist in
      Japanese melanoma patients, however, the cell growth signaling may be regulated
      by not only these mutated genes, but by other unknown regulatory factors, which
      may affect the prognosis of melanoma. 

PMID- 25766130
TI  - Is Repeated Fine-Needle Aspiration Biopsy of Nodules with Bethesda Category III
      (Atypia of Undetermined Significance/Follicular Lesion of Undetermined
      Significance) Associated with a Decreased or Increased Malignancy Rate?

PMID- 25766131
TI  - Functionalisation of hollow gold nanospheres for use as stable, red-shifted SERS
      nanotags.
AB  - Hollow Gold Nanospheres (HGNs) exhibit a unique combination of properties which
      provide great scope for their use in many biomedical applications. However, they
      are highly unstable to changes in their surrounding environment and have a
      tendency to aggregate, particularly when exposed to high salt concentrations or
      changes in pH which is not ideal for applications such as cell imaging and drug
      delivery where stable solutions are required for efficient cellular uptake.
      Therefore there is a significant need to find a suitable stabilising agent for
      HGNs, however potential stabilising agents for these nanostructures have not
      previously been compared. Within this work we present an improved method for
      stabilising HGNs which simultaneously shifts the SPR from around 700 nm to 800 nm
      or greater. Herein, we compare three different materials which are commonly used
      as stabilising agents; polymers, sugars and silica in order to determine the
      optimum stabilising agent for HGNs. Analysis was performed using extinction
      spectroscopy and dynamic light scattering, supported with SEM imaging. Results
      showed PEG to be the most suitable stabilising agent for HGNs displaying both an
      increased stability to changes in salt concentration and pH as well as increased
      long term stability in solution. Furthermore, we demonstrate that in addition to
      increased stability, SERS detection can be achieved at both 1064 nm and 785 nm
      excitation. This combination of improved stability with a SPR in the NIR region
      along with SERS detection demonstrates the great potential for these
      nanostructures to be used in applications such as biological SERS imaging and
      drug delivery. 

PMID- 25766132
TI  - Polyphosphate, an active molecule derived from probiotic Lactobacillus brevis,
      improves the fibrosis in murine colitis.
AB  - Inflammatory bowel disease frequently causes intestinal obstruction because of
      extensive fibrosis. This study investigated whether polyphosphate (poly P), an
      active molecule derived from Lactobacillus brevis, could improve the fibrosis in
      a model of chronic colitis. In this study, dextran sodium sulfate (DSS)-induced
      chronic colitis models and trinitrobenzene sulfonic acid (TNBS)-induced colitis
      models were used as models of fibrosis. To clarify the mechanism responsible for
      the observed effects, Caco-2/brush border epithelial (BBE) and naive T helper
      lymphocyte (THP)-1 cells were treated with lipopolysaccharide (LPS) to induce
      inflammation. Non-cancer human colon fibroblast (CCD-18) cells were treated with
      transforming growth factor beta 1 (TGF-beta1) to induce fibrosis. The expression
      levels of fibrosis- and inflammation-associated molecules were evaluated by both
      a Western blotting analysis and reverse transcriptase-polymerase chain reaction
      (RT-PCR). The histologic inflammation and fibrosis were significantly improved in
      the group administered poly P in both the DSS and TNBS colitis models. The levels
      of interleukin 1beta (IL-1beta) and tumor necrosis factor alpha (TNF-alpha) were
      significantly decreased by poly P treatment. The expression levels of TGF-beta1
      and collagens in the colitis mice were decreased by poly P. The LPS-induced
      expressions of IL-1beta and TGF-beta1 in Caco-2/BBE cells and of TNF-alpha in THP
      1 cells were reduced by poly P treatment. Poly P did not affect the expression of
      collagens and connective tissue growth factor in the CCD-18 cells. In conclusion,
      poly P suppresses intestinal inflammation and fibrosis by downregulating the
      expression of inflammation- and fibrosis-associated molecules in the intestinal
      epithelium. The administration of poly P is therefore a novel option to treat
      fibrosis because of chronic intestinal inflammation.

PMID- 25766134
TI  - Success with SNRS grants.

PMID- 25766133
TI  - Alteration of enteric monoamines with monoamine receptors and colonic dysmotility
      in 6-hydroxydopamine-induced Parkinson's disease rats.
AB  - Constipation is common in Parkinson's disease (PD), in which monoamines (dopamine
      [DA], norepinephrine [NE], and 5-hydroxytryptamine [5-HT]) play an important
      role. Rats microinjected with 6-hydroxydopamine (6-OHDA) into the bilateral
      substantia nigra (SN) exhibit constipation, but the role of monoamines and their
      receptors is not clear. In the present study, colonic motility, monoamine
      content, and the expression of monoamine receptors were examined using strain
      gauge force transducers, ultraperformance liquid chromatography tandem mass
      spectrometry, immunofluorescence, and Western blot. The 6-OHDA rats displayed a
      significant reduction in dopaminergic neurons in the SN and a decreased time on
      rota-rod test and a marked decrease in daily fecal production and fecal water
      content. The amplitude of colonic spontaneous contraction was obviously decreased
      in 6-OHDA rats. Blocking D1-like receptor and beta3-adrenoceptor (beta3-AR)
      significantly reduced the inhibition of DA and NE on the colonic motility,
      respectively, whereas the 5-HT and 5-HT4 receptor agonists promoted the colonic
      motility. Moreover, DA content was increased in the colonic muscularis externa of
      6-OHDA rats. The protein expression of beta3-ARs was notably upregulated, but 5
      HT4 receptors were significantly decreased in the colonic muscularis externa of 6
      OHDA rats. We conclude that enhanced DA and beta3-ARs and decreased 5-HT4
      receptors may be contributed to the colonic dysmotility and constipation observed
      in 6-OHDA rats.

PMID- 25766136
TI  - Controlled synthesis of Fe3O4/ZIF-8 nanoparticles for magnetically separable
      nanocatalysts.
AB  - Fe3O4/ZIF-8 nanoparticles were synthesized through a room-temperature reaction
      between 2-methylimidazolate and zinc nitrate in the presence of Fe3O4
      nanocrystals. The particle size, surface charge, and magnetic loading can be
      conveniently controlled by the dosage of Zn(NO3)2 and Fe3O4 nanocrystals. The as
      prepared particles show both good thermal stability (stable to 550  degrees C)
      and large surface area (1174 m(2) g(-1)). The nanoparticles also have a
      superparamagnetic response, so that they can strongly respond to an external
      field during magnetic separation and disperse back into the solution after
      withdrawal of the magnetic field. For the Knoevenagel reaction, which is
      catalyzed by alkaline active sites on external surface of catalyst, small
      Fe3O4/ZIF-8 nanoparticles show a higher catalytic activity. At the same time, the
      nanocatalysts can be continuously used in multiple catalytic reactions through
      magnetic separation, activation, and redispersion with little loss of activity.

PMID- 25766137
TI  - CKD in disadvantaged populations.

PMID- 25766138
TI  - Genome-scale analysis reveals a role for NdgR in the thiol oxidative stress
      response in Streptomyces coelicolor.
AB  - BACKGROUND: NdgR is an IclR-type transcription factor that regulates leucine
      biosynthesis and other metabolic pathways in Streptomyces coelicolor. Recent
      study revealed that NdgR is one of the regulatory targets of SigR, an oxidative
      stress response sigma factor, suggesting that the NdgR plays an important
      physiological role in response to environmental stresses. Although the regulatory
      functions of NdgR were partly characterized, determination of its regulon is
      required for better understanding of the transcriptional regulatory network
      related with the oxidative stress response. RESULTS: We determined genome-wide
      binding loci of NdgR by using chromatin immunoprecipitation coupled with
      sequencing (ChIP-seq) and explored its physiological roles. The ChIP-seq profiles
      revealed 19 direct binding loci with a 15-bp imperfect palindromic motif,
      including 34 genes in their transcription units. Most genes in branched-chain
      amino acid and cysteine biosynthesis pathways were involved in the NdgR regulon.
      We proved that ndgR is induced by SigR under the thiol oxidation, and that an
      ndgR mutant strain is sensitive to the thiol oxidizing agent, diamide. Through
      the expression test of NdgR and the target genes for NdgR under diamide
      treatment, regulatory motifs were suggested. Interestingly, NdgR constitutes two
      regulatory motifs, coherent and incoherent feed-forward loops (FFL), in order to
      control its regulon under the diamide treatment. Using the regulatory motifs,
      NdgR regulates cysteine biosynthesis in response to thiol oxidative stress,
      enabling cells to maintain sulfur assimilation with homeostasis under stress
      conditions. CONCLUSIONS: Our analysis revealed that NdgR is a global
      transcriptional regulator involved in the regulation of branched-chain amino
      acids biosynthesis and sulphur assimilation. The identification of the NdgR
      regulon broadens our knowledge regarding complex regulatory networks governing
      amino acid biosynthesis in the context of stress responses in S. coelicolor.

PMID- 25766139
TI  - Psychometric Evaluation of Lexical Diversity Indices: Assessing Length Effects.
AB  - PURPOSE: Several novel techniques have been developed recently to assess the
      breadth of a speaker's vocabulary exhibited in a language sample. The specific
      aim of this study was to increase our understanding of the validity of the scores
      generated by different lexical diversity (LD) estimation techniques. Four
      techniques were explored: D, Maas, measure of textual lexical diversity, and
      moving-average type-token ratio. METHOD: Four LD indices were estimated for
      language samples on 4 discourse tasks (procedures, eventcasts, story retell, and
      recounts) from 442 adults who are neurologically intact. The resulting data were
      analyzed using structural equation modeling. RESULTS: The scores for measure of
      textual lexical diversity and moving-average type-token ratio were stronger
      indicators of the LD of the language samples. The results for the other 2
      techniques were consistent with the presence of method factors representing
      construct-irrelevant sources. CONCLUSION: These findings offer a deeper
      understanding of the relative validity of the 4 estimation techniques and should
      assist clinicians and researchers in the selection of LD measures of language
      samples that minimize construct-irrelevant sources.

PMID- 25766140
TI  - Presynaptic architecture of the larval zebrafish neuromuscular junction.
AB  - This article shows the ultrastructural architecture of larval zebrafish (Danio
      rerio) neuromuscular junctions in three dimensions. We compare classical electron
      microscopy fixation techniques with high-pressure freezing followed by freeze
      substitution (HPF/FS) in combination with electron tomography. Furthermore, we
      compare the structure of neuromuscular junctions in 4- and 8-dpf zebrafish larvae
      with HPF/FS because this allows for close-to-native ultrastructural preservation.
      We discovered that synaptic vesicles of 4-dpf zebrafish larvae are larger than
      those of 8-dpf larvae. Furthermore, we describe two types of dense-core vesicles
      and quantify a filamentous network of small filaments interconnecting synaptic
      vesicles as well as tethers connecting synaptic vesicles to the presynaptic cell
      membrane. In the center of active zones, we found elaborate electron-dense
      projections physically connecting vesicles of the synaptic vesicle pool to the
      presynaptic membrane. Overall this study establishes the basis for systematic
      comparisons of synaptic architecture at high resolution in three dimensions of an
      intact vertebrate in a close-to-native state. Furthermore, we provide
      quantitative information that builds the basis for diverse systems biology
      approaches in neuroscience, from comparative anatomy to cellular simulations.

PMID- 25766141
TI  - Viremia levels in hepatitis C infection among Egyptian blood donors and
      implications for transmission risk with different screening scenarios.
AB  - BACKGROUND: Knowledge about the viral load (VL) distributions in different stages
      of hepatitis C virus (HCV) infection is essential to compare the efficacy of
      serologic screening and nucleic acid testing (NAT) in preventing transfusion
      transmission risk. We studied HCV-RNA levels in Egyptian blood donors in the
      preseroconversion window period (WP) and in later anti-HCV-positive stages of
      infection. STUDY DESIGN AND METHODS: Subsets of individual-donation (ID)-NAT and
      anti-HCV-yield samples from a screening study among 119,756 donors were tested
      for VL by quantitative polymerase chain reaction (qPCR). Low viremia levels below
      the quantification limit of qPCR were determined by probit analysis using the
      proportion of reactive results on replicate NATs. Poisson distribution statistics
      were used to estimate transmission risk in different stages of HCV infection
      based on 50% minimum infectious doses (MID50 ) of 3.2 (1-10) and 316 (100-1000)
      virions in the absence and presence of anti-HCV, respectively. RESULTS: Rates of
      total HCV infections and WP-NAT-yield donations in two Egyptian blood centers
      varied between 2.6% to 4.5% and 1:3100 to 1:9500, respectively. VLs ranged from
      82 to 3 * 10(7) copies/mL in WP and from fewer than 1600 to 1.6 * 10(6) copies/mL
      in anti-HCV-positive carrier donations. Only two (1.1%) of 175 donors with
      probable resolved infection had detectable RNA on replicate testing (estimated
      VLs of 0.5 and 1.8 copies/mL). This translates to an estimated transmission risk
      of 0.028% if ID-NAT-nonreactive, anti-HCV-positive donations would be used for
      RBC transfusions. CONCLUSION: Almost 99% of anti-HCV-reactive donations without
      detectable HCV-RNA on initial ID-NAT screening had eradicated the virus from the
      circulation, while 1% had extremely low VLs and are likely not infectious. The
      incremental safety offered by serologic testing of ID-NAT-screened blood seems
      minimal.

PMID- 25766142
TI  - Comparison of experimental respiratory tularemia in three nonhuman primate
      species.
AB  - Tularemia is a zoonotic disease caused by Francisella tularensis, which is
      transmitted to humans most commonly by contact with infected animals, tick bites,
      or inhalation of aerosolized bacteria. F. tularensis is highly infectious via the
      aerosol route; inhalation of as few as 10-50 organisms can cause pneumonic
      tularemia. Left untreated, the pneumonic form has more than >30% case-fatality
      rate but with early antibiotic intervention can be reduced to 3%. This study
      compared tularemia disease progression across three species of nonhuman primates
      [African green monkey (AGM), cynomolgus macaque (CM), and rhesus macaque (RM)]
      following aerosolized F. tularensis Schu S4 exposure. Groups of the animals
      exposed to various challenge doses were observed for clinical signs of infection
      and blood samples were analyzed to characterize the disease pathogenesis. Whereas
      the AGMs and CMs succumbed to disease following challenge doses of 40 and 32
      colony forming units (CFU), respectively, the RM lethal dose was 276,667 CFU.
      Following all challenge doses that caused disease, the NHPs experienced weight
      loss, bacteremia, fever as early as 4 days post exposure, and tissue burden.
      Necrotizing-to-pyogranulomatous lesions were observed most commonly in the lung,
      lymph nodes, spleen, and bone marrow. Overall, the CM model consistently
      manifested pathological responses similar to those resulting from inhalation of
      F. tularensis in humans and thereby most closely emulates human tularemia
      disease. The RM model displayed a higher tolerance to infection and survived
      exposures of up to 15,593 CFU of aerosolized F. tularensis.

PMID- 25766143
TI  - Resistance is not futile: gliotoxin biosynthesis, functionality and utility.
AB  - Gliotoxin biosynthesis is encoded by the gli gene cluster in Aspergillus
      fumigatus. The biosynthesis of gliotoxin is influenced by a suite of
      transcriptionally-active regulatory proteins and a bis-thiomethyltransferase. A
      self-protection system against gliotoxin is present in A. fumigatus. Several
      additional metabolites are also produced via the gliotoxin biosynthetic pathway.
      Moreover, the biosynthesis of unrelated natural products appears to be influenced
      either by gliotoxin or by the activity of specific reactions within the
      biosynthetic pathway. The activity of gliotoxin against animal cells and fungi,
      often mediated by interference with redox homeostasis or protein modification, is
      revealing new metabolic interactions within eukaryotic systems. Nature has
      provided a most useful natural product with which to reveal some of its many
      molecular secrets. 

PMID- 25766145
TI  - How a zigzag carbon nanotube grows.
AB  - Owing to the unique structure of zigzag (ZZ) carbon nanotubes (CNTs), their ring
      by-ring growth behavior is different from that of chiral or armchair (AC) CNTs,
      on the rims of which kinks serve as active sites for carbon attachment. Through
      first-principle calculations, we found that, because of the high energy barrier
      of initiating a new carbon ring at the rim of a ZZ CNT, the growth rate of a ZZ
      CNT is proportional to its diameter and significantly (10-1000 times) slower than
      that of other CNTs. This study successfully explained the broad experimental
      observation of the lacking of ZZ CNTs in CNT samples and completed the theory of
      CNT growth. 

PMID- 25766146
TI  - Will someone explain please?

PMID- 25766147
TI  - Newer oral anticoagulants.

PMID- 25766144
TI  - HIV cell-to-cell transmission: effects on pathogenesis and antiretroviral
      therapy.
AB  - HIV spreads more efficiently in vitro when infected cells directly contact
      uninfected cells to form virological synapses. A hallmark of virological synapses
      is that viruses can be transmitted at a higher multiplicity of infection (MOI)
      that, in vitro, results in a higher number of proviruses. Whether HIV also
      spreads by cell-cell contact in vivo is a matter of debate. Here we discuss
      recent data that suggest that contact-mediated transmission largely manifests
      itself in vivo as CD4+ T cell depletion. The assault of a cell by a large number
      of incoming particles is likely to be efficiently sensed by the innate cellular
      surveillance to trigger cell death. The large number of particles transferred
      across virological synapses has also been implicated in reduced efficacy of
      antiretroviral therapies. Thus, antiretroviral therapies must remain effective
      against the high MOI observed during cell-to-cell transmission to inhibit both
      viral replication and the pathogenesis associated with HIV infection. 

PMID- 25766148
TI  - Pharmaceuticals: timing of extraction.

PMID- 25766149
TI  - Oral surgery: checklists and double checks.

PMID- 25766150
TI  - Oral health: reverse referral.

PMID- 25766151
TI  - Turn off the tap.

PMID- 25766152
TI  - Orthodontics: fast and furious.

PMID- 25766153
TI  - Anaesthesia: bilateral guidelines.

PMID- 25766154
TI  - Hospital dentistry: publicise emergency options.

PMID- 25766155
TI  - Standard manual brushes.

PMID- 25766156
TI  - Careers: what is community dentistry?

PMID- 25766157
TI  - Call for coordinated offensive on obesity and dental decay.

PMID- 25766160
TI  - BDA Museum: 'Father of BDA' turns 200.

PMID- 25766161
TI  - BRITISH DENTAL ASSOCIATION (THE 'COMPANY') (REGISTERED IN ENGLAND AND WALES WITH
      COMPANY NUMBER 14161): Notice of Annual General Meeting.

PMID- 25766162
TI  - David Arkush.

PMID- 25766163
TI  - Pre- and postoperative management techniques. Before and after. Part 1: medical
      morbidities.
AB  - This article provides readers with an overview of available evidence in relation
      to providing care to patients in different medical circumstances within oral
      surgery. There is evidence available to support discussions with patients taking
      particular medications (such as bisphosphonates, anticoagulants and
      corticosteroids) and also to try to prevent certain complications (such as 'dry
      socket'). In order to reduce the risks of potential morbidities, either
      perioperatively or postoperatively, operators must use high-quality, reliable and
      informed protocols, management techniques, advice and interventions to provide
      patients with the best care. These are used both preoperatively and
      postoperatively and patients should be consented appropriately, in a manner
      tailored to their own individual circumstances, but also using available evidence
      to explain the benefits and harms of any given procedure. In this short series we
      will outline and discuss common pre- and postoperative management techniques,
      protocols and instructions, and the evidence available to support these. 

PMID- 25766164
TI  - Pre- and postoperative management techniques. Before and after. Part 2: the
      removal of third molars.
AB  - This article aims to highlight the strengths and weaknesses within the selected
      evidence to aid readers in clinical decision-making when managing patients before
      and after third molar surgery. Preoperative methods to prevent nerve damage,
      including the use of computed tomography (CT), are discussed. Preoperative
      considerations are also summarised, including risk factors such as increasing the
      occurrence of nerve deficit, weakness and damage, and the role of cone beam CT
      and when this should be used. The postoperative complications pain, swelling and
      infection are considered and the available evidence for the use of different
      protocols, regimes and combinations of therapies summarised. 

PMID- 25766166
TI  - Corrigendum. Practice article (BDJ 2015; 218: 69-74). A review of dental
      treatment of head and neck cancer patients, before, during and after
      radiotherapy: part 2.

PMID- 25766165
TI  - Fractured root tips during dental extractions and retained root fragments. A
      clinical dilemma?
AB  - Root tip fracture can occur during the extraction of teeth. The clinician must
      then decide to either leave the root fragment in situ, or to attempt its removal.
      A similar decision is made when retained root fragments are found incidentally on
      oral radiographs. The prevalence of retained root fragments is reported as 11
      37%. This article aims to highlight the risk benefit matrix of the removal or
      retention of retained root fragments, in light of the present evidence base. 

PMID- 25766170
TI  - Summary of: Implant surface characteristics and their effect on osseointegration.

PMID- 25766171
TI  - Summary of: Is there a role for community pharmacists in promoting oral health?

PMID- 25766172
TI  - Would you choose an academic career? Views of current dental clinical academic
      trainees.
AB  - OBJECTIVE: To determine the views of current dental clinical academic trainees
      regarding their current posts. DESIGN: Online questionnaire emailed to 51 dental
      academic trainees. Survey results were collected over a six-week period. Eighteen
      closed statement questions were included using a five-point scale from 'strongly
      agree' to 'strongly disagree'. All questions had a section for open text
      comments. RESULTS: The response rate for the survey was 73%. A total of 38% were
      male and 62% female. Just under half of the sample (43%) had a higher teaching
      qualification. The majority of trainees were from oral surgery (22%), closely
      followed by restorative and dental public health (both 14%). The main reason
      trainees stated for choosing an academic post was to be involved in research
      (68%). The majority of dental clinical academic trainees would recommend a career
      in academia. CONCLUSION: The majority of dentistry's academic trainees (73%)
      would recommend an academic career to their peers, a positive change in the
      culture of modern clinical academia.

PMID- 25766173
TI  - The importance of, and the benefits derived from, forward dental peripatetic
      clinics in Afghanistan.
AB  - The majority of dental care for military personnel is carried out in clinics that
      would be familiar to all dental professionals. In times of conflict, however,
      dental care is often required to travel to those in need. Dental morbidity has a
      detrimental effect on a fighting force, both at the personal level and for
      maintaining combat efficiency. In Afghanistan, two main dental centres provided
      the majority of emergency care to coalition forces, but from March to September
      2012, 23 peripatetic clinics also took place with 472 dental casualties treated.
      Assessment of these peripatetic clinics demonstrates both quantitative and
      qualitative benefits. Return travel to main base clinics takes between three to
      five days. If all personnel during this period had attended a main base and
      returned to their duty station in only three days, over 1,000 duty days would
      have been lost. This compares to the 32 days actually lost by attending
      peripatetic clinics instead and illustrates the considerable time that was saved.
      Additionally, time spent travelling in a hostile environment is also time at risk
      of attack. Forty-one anonymous comments about the clinics were left by personnel.
      All were positive and enthusiastic. The results of this review demonstrate that
      these clinics save considerable mission time, reduce risk to military personnel,
      and were greatly valued by those suffering dental problems. 

PMID- 25766174
TI  - Corrigendum. Practice article (BDJ 2015; 218: 151-156). The developing occlusion
      of children and young people in general practice: when to watch and when to
      refer.

PMID- 25766191
TI  - Special care dentistry: two sides of a coin.
AB  - Facilitating oral care for patients with a disability or impairment is affected
      by considerations for the patient and the actions of the dental team. This
      article, and the associated session at the 2015 British Dental Conference
      &Exhibition, reviews the wide range of areas that special care dentistry covers.
      The article and session will also provide tips and techniques for providing
      special adjustments and how to understand the expectations of patients with
      additional needs. 

PMID- 25766192
TI  - John Anthony Pettifer.

PMID- 25766193
TI  - Andy Williams.

PMID- 25766194
TI  - Is there a role for community pharmacists in promoting oral health?
AB  - AIM: The main aim of the present study was to investigate whether pharmacists
      recognised that they have a role in the promotion of oral health advice within
      the community. METHODS: A cross sectional survey was conducted using a structured
      questionnaire which was distributed to randomly selected pharmacies (n = 1,500)
      in the London area. RESULTS: Six hundred and forty-five pharmacies (43%)
      responded to the initial invitation and 589 (39%) of pharmacy participants
      acknowledged that pharmacists should have a role in oral health promotion.
      Participants from 354 pharmacies (23.6%) subsequently agreed to complete the
      questionnaire. Of those pharmacies completing the questionnaire, 99.4% of the
      pharmacy participants recognised that there was a role for pharmacists in oral
      health promotion. Although 91.5% of the pharmacists reported a fairly high level
      of knowledge for most of the common oral conditions, they also indicated that
      they were interested in receiving further training on oral conditions through
      continuing professional development (CPD) courses. A number of the pharmacies
      (72.5%) expressed a willingness to incorporate oral health promotion within the
      NHS pharmacy contract. CONCLUSION: Pharmacies may be used effectively in oral
      health promotion by virtue of their frequent contact with members of public. As a
      result of their established role in promoting and improving the health within the
      community, it may possible to incorporate oral health within the existing NHS
      contract.

PMID- 25766195
TI  - Intravenous sedation as an adjunct to advanced comprehensive dental implantology:
      the patient's perspective and operator satisfaction.
AB  - OBJECTIVES: The aim of this three-year study was to evaluate whether elective
      comprehensive dental implant procedures involving guided bone and soft tissue
      regeneration carried out under intravenous sedation (midazolam) would be
      influenced by patient self-reported pre-operative anxiety levels; age and gender;
      effect the level of sedation with respect to the amount of sedative administered
      and the time taken in the procedures; effect patient intra-operative cooperation,
      and post-operative levels of patient satisfaction; influence further acceptance
      of dental implant surgical procedures; effect intra-operative surgeon
      satisfaction and consequently his/her post-operative sense of achievement.Design
      Single centre general dental practice, open study as a clinical audit. METHOD:
      One hundred and seventy-three consecutive patients undergoing prolonged surgical
      procedures involving dental implantology with the adjunctive facility of
      intravenous sedation were monitored with respect to self-reported levels of
      anxiety. Vital signs of heart rate, mean systolic and diastolic blood pressure
      and arterial oxygen saturation were recorded and monitored pre-intra- and post
      surgery. A post-operative questionnaire was completed as to the perceptions of
      the level of sedation. RESULTS: A distinct relationship between self-reported pre
      operative anxiety levels, age and gender were recorded - the younger the age, the
      higher the anxiety, with females dominating. Females required more midazolam than
      males. However, the analysis of the data as a whole, incorporating both genders,
      revealed a non-significant correlation result. The correlation between the
      midazolam dosage and the Corah anxiety score produced a p value result of: r
      (161) = 0.008, p <0.01. Forty-four percent of the patients described themselves
      as having 'high anxiety and fear of the dentist', however, 99.4% of the patients
      answered 'yes' to having sedation again in the future. For the purpose of this
      study, detailed consideration was given to the gender specific results in order
      to reveal a wider understanding of who poses as a 'cooperative patient'.
      CONCLUSIONS: The results should prompt a rethink as to who a cooperative patient
      is, and whether the self-assessed level of anxiety will influence further
      acceptance of dental implant surgical procedures under intravenous sedation.

PMID- 25766197
TI  - Halide abstraction from halogenated acetate ligands by actinyls: a competition
      between bond breaking and bond making.
AB  - Transfer of halogen atoms from halogenated acetate ligands, CX3CO2 (X = F, Cl,
      Br), to actinyls, AnO2(2+) (An = U, Np, Pu) is stimulated by collision-induced
      dissociation (CID) in a quadrupole ion trap. CID of [AnO2(CF3CO2)3](-) complexes
      results exclusively in F atom transfer, concomitant with elimination of CF2CO2,
      to produce [(CF3CO2)2AnO2F](-), [(CF3CO2)AnO2F2](-), and [AnO2F3](-). This
      contrasts with CID of transition metal fluoroacetates for which CO2-elimination
      to produce organometallics is an important pathway, a disparity that can be
      attributed to the differing bond dissociation energies (BDEs) of the created
      metal-carbon and metal-fluorine bonds. The dominant pathway for CID of
      [AnO2(CF3CO2)(CCl3CO2)(CBr3CO2)](-) is Br-atom transfer to produce
      [(CF3CO2)(CCl3CO2)AnO2Br](-). The preferential formation of bromides, despite
      that the BDEs of An-F bonds are substantially greater than those of An-Br bonds,
      is attributed to the offsetting effect of higher BDEs for C-F versus C-Br bonds.
      The results for the trihaloacetates are similar for uranyl, neptunyl and
      plutonyl, indicating that for all three the An-X bond dissociation energies are
      sufficiently high that X atom transfer is overwhelmingly dominant. CID of
      [UO2(CH2XCO2)2(CX3CO2)](-) (X = F, Cl, Br) resulted in F-transfer only from
      CH2XCO2, but Cl- and Br-transfer from both CH2XCO2 and CX3CO2, a manifestation of
      the characteristic increase in BDE[C-F] in CHx-nFn species as n increases; the
      overall thermochemistry determines the observed CID processes, providing clear
      distinctions between fluorides and chlorides/bromides. The results of this work
      reveal the propensity of the actinides to form strong bonds with halogens, and
      suggest that there is not a large variation in actinyl-halogen BDEs between
      uranyl, neptunyl, and plutonyl. 

PMID- 25766198
TI  - A review of the risks and consequences of adolescent pregnancy.
AB  - OBJECTIVE: To evaluate the risks and consequences of young maternal age on both
      the mother and the newborn. STUDY DESIGN: A comprehensive literature review on
      the risks and consequences of adolescent pregnancy was performed. RESULTS: Young
      maternal age is associated with an increased risk of maternal anemia, infections,
      eclampsia and preeclampsia, emergency cesarean delivery, postpartum depression
      and inadequate breastfeeding initiation. Infants of teenage mothers are more
      likely to be premature and have a low birth weight, and are at an increased risk
      for respiratory distress syndrome and autism later in life. CONCLUSIONS:
      Adolescent pregnancy is a prevalent phenomenon associated with increased risks of
      both maternal and neonatal complications during and after pregnancy. Being aware
      of such adverse outcomes is imperative to improving prenatal and perinatal care.
      Pregnancy progression can also be influenced by the mother's culture,
      environment, and economic status; advancement in which may be a possible course
      for future improvement.

PMID- 25766196
TI  - Implant surface characteristics and their effect on osseointegration.
AB  - AIM: The aim of this literature review is to find current knowledge of dental
      implants focusing on materials, designs and surface modifications and to
      understand which implant surfaces have more predictable clinical outcomes.
      RESEARCH MATERIAL AND METHODS: An electronic search using PubMed/Medline, Scopus
      and The Cochrane Library databases from 1950 onwards was conducted using keywords
      and terms. Published papers were then obtained online or from specialist
      libraries. References from individual published papers were also searched for
      relevant publications. RESULTS: Different designs, materials and methods to
      modify surfaces of implants have been discussed in this paper. Many laboratory
      studies using animal models reported improved biological outcomes with surface
      modification of implants at the microscopic level. Despite pure titanium being
      commercially the prime material of choice, ceramics have the potential to become
      the next generation of dental implants. Presently there is not sufficient
      scientific evidence for routine use of ceramic implants. CONCLUSIONS: Pure
      titanium is the ideal material for implants. Rough implant surfaces are believed
      to deliver better osseointegration compared with smooth surfaces however, results
      from different studies vary. It is not clear which combination of different
      surface modifications provide a more predictable outcome. More standardised high
      quality prospective studies are required to prove which implant surfaces have the
      optimum properties for replacing missing teeth.

PMID- 25766199
TI  - Factors influencing independent oral feeding in preterm infants.
AB  - OBJECTIVE: Determine the mean post-menstrual age when preterm infants attain
      independent oral feeding skills and whether gestational age, common neonatal
      morbidities, gender, race, delivery route, or birth year affects this reflex.
      METHODS: A retrospective chart review of 2700 preterm infants, born before 37
      weeks gestational age admitted to a level III NICU between January 1978 and July
      2013, to determine the post-menstrual age when independent oral feedings occur.
      RESULTS: Mean post-menstrual age at achievement of independent oral feeding was
      36 + 4/7 weeks +/- 14 days. Gestational age under 29 weeks correlated with
      delayed post-menstrual age at achievement of independent oral feeding at 37 + 3/7
      weeks versus 36 + 1/7 weeks for gestational age 29-33 weeks and 36 + 3/7 weeks
      for late preterm infants (p < 0.0001). Preterm infants with certain morbidities
      experienced a delay in independent oral feeding: necrotizing enterocolitis at 38
      + 6/7 weeks (p < 0.0001), bronchopulmonary dysplasia at 38 + 1/7 weeks (p <
      0.0001), severe intraventricular hemorrhage at 37 + 6/7 weeks (p < 0.001).
      Preterm infants born before the year 2000 achieved independent oral feeding two
      days later than preterm infants born since the year 2000 (p < 0.0001). Preterm
      infants delivered vaginally achieved independent oral feeding three days sooner
      than infants delivered via c-section (p < 0.0001). Female infants orally fed one
      day sooner than male preterm infants (p = 0.0008). CONCLUSIONS: Preterm infants
      achieve independent oral feeding at 36 + 4/7 weeks. Factors negatively
      influencing when the preterm infant will achieve independent oral feeding include
      gestational age under 29 weeks and major morbidities, whereas vaginal delivery
      and ongoing advances in neonatal care may accelerate the transition to
      independent oral feeding.

PMID- 25766200
TI  - Gestational autoimmune disease in newborns with an indeterminate cause of death
      following a complete autopsy.
AB  - Gestational alloimmune liver disease (GALD) is the result of neonatal complement
      mediated severe liver injury mediated by maternal alloantibodies, which is
      detected by immunohistochemistry staining for the complement C5b-9 complex. GALD
      leads to the neonatal hemochromatosis (NH) phenotype, which also shows
      extrahepatic siderosis, and can result in neonatal death. At autopsy, the
      histologic damage of the liver in GALD may be subtle and misinterpreted as non
      specific post-mortem changes, resulting in the cause of death classified as
      indeterminate. We reviewed the pathologic diagnoses from autopsy material from
      1996 to 2011 of infants 0-90 days of age from our institution. Liver samples were
      stained with H&E, trichrome and for C5b-9. 13 cases originally diagnosed as
      indeterminate cause of death were identified and divided in 3 groups: (1) No
      clinical or autopsy-derived diagnoses (n = 7), (2) Defined clinical diagnoses but
      no cause of death determined at autopsy (n = 2), and (3) Liver disease, but no
      clinical or autopsy diagnoses to establish the cause of the liver injury (n = 4).
      On reexamination, all group 1 and 3 cases were reclassified as GALD, based on a
      positive C5b-9 stain. Group 2 cases were not GALD, retaining the original,
      clinically-based cause of death. We conclude that, in cases of indeterminate
      cause of neonatal death, very careful examination for hepatocyte injury/necrosis,
      extrahepatic siderosis, liver fibrosis and/or C5b-9 stain should be considered.

PMID- 25766201
TI  - Placental pathology in asphyxiated newborns treated with therapeutic hypothermia.
AB  - OBJECTIVE: To describe the placental findings in asphyxiated newborns treated
      with hypothermia and to determine their association with the presence and
      severity of later brain injury. METHODS: Prospective cohort study of the
      placentas of asphyxiated newborns treated with hypothermia, in whom later brain
      injury was defined by brain imaging and/or autopsy results. RESULTS: Of the 142
      asphyxiated newborns meeting the criteria for hypothermia, 73% had placenta and
      brain MRI/autopsy available for analysis. Fifty-one percent of these newborns
      developed brain injury. Sixty-five percent had microscopic placental findings
      involving the fetal vascular supply, which were comparable in asphyxiated
      newborns developing or not developing brain injury. Among the asphyxiated
      newborns with normal placental growth, the placental microscopic findings tended
      to be more common in those developing brain injury compared to those who did not:
      chorionic plate meconium in 50% compared to 36%, chorioamnionitis in 75% compared
      to 44%, and villitis of unknown etiology in 67% compared to 33%, but this did not
      reach statistical significance. CONCLUSIONS: Antenatal placental processes are
      common in term asphyxiated newborns treated with hypothermia. The placenta of
      each asphyxiated term newborn treated with hypothermia should be carefully
      examined to better understand its role in the progression from perinatal
      depression to brain injury.

PMID- 25766202
TI  - Noninvasive imaging of peripheral nerves.
AB  - Recent developments in the field of peripheral nerve imaging extend the
      capabilities of imaging modalities to assist in the diagnosis and treatment of
      patients with peripheral nerve maladies. Methods such as magnetic resonance
      imaging (MRI) and its derivative diffusion tensor imaging (DTI), ultrasound (US)
      and positron emission tomography (PET) are capable of assessing nerve structure
      and function following injury and relating the state of the nerve to
      electrophysiological and histological analysis. Of the imaging methods surveyed
      here, each offered unique and interesting advantages related to the field. MRI
      offered the opportunity to visualize immune activity on the injured nerve
      throughout the course of the regeneration process, and DTI offered numerical
      characterization of the injury and the ability to develop statistical bases for
      diagnosing injury. US extends imaging to the treatment phase by enabling more
      precise analgesic applications following surgery, and PET represents a novel
      method of assessing nerve injury through analysis of relative metabolism rates in
      injured and healthy tissue. Exciting new possibilities to enhance and extend the
      abilities of imaging methods are also discussed, including innovative contrast
      agents, some of which enable multimodal imaging approaches and present
      opportunities for treatment application.

PMID- 25766203
TI  - PIF direct immune regulation: Blocks mitogen-activated PBMCs proliferation,
      promotes TH2/TH1 bias, independent of Ca(2+).
AB  - PreImplantation Factor (PIF(9&15)) secreted by viable embryos exerts an essential
      transplant acceptance and immune regulatory role in pregnancy. Synthetic PIF
      replicates endogenous PIF's effect in pregnant and non-pregnant immune disorder
      models. PIF binds macrophages to regulate CD3/CD28-induced T-cell response. We
      present evidence that PIF regulates the co-stimulatory T-cell receptor, CD2,
      which binds to and is activated by phytohemagglutinin (PHA), a potent mitogen,
      confirming PIF's ability to systemically respond to diverse immune stimulants.
      PIF's effect on PHA-activated PBMC (male and non-pregnant females) proliferation
      and cytokine secretion was tested, showing that both PIF(9&15) block PHA-induced
      PBMC proliferation and promote anti-inflammatory IL10 secretion, while reducing
      pro-inflammatory IFNgamma secretion. Thus favoring a T(H)2 cytokine bias. Surface
      plasmon resonance spectroscopy, immunocytochemistry and Flex station experiments
      reveal that PIF effect is direct. PIF targets intracellular targets but does not
      affect early Ca(2+) mobilization. By promoting the CD2 receptor in activated T
      cells and through inhibition of co-ligand CD58 expression, PIF regulates antigen
      presenting cell (APC)-T-cell interactions required for PHA action. Structure
      based design demonstrated that PIF15 offers improved target specificity as
      compared to PIF9. Collectively, PIF directly regulates mitogen-induced PBMC
      activation. Results support PIF translation for therapy of immune disorders.

PMID- 25766204
TI  - Anti-CD83 promotes IgG1 isotype switch in marginal zone B cells in response to TI
      2 antigen.
AB  - CD83 is a transmembrane glycoprotein that is rapidly up-regulated on activated B
      cells. Although CD83 itself is incapable to transduce intracellular signaling, it
      acts as a negative regulator of B cell function. We have recently described that
      a single application of anti-CD83 antibody results in dramatically enhanced
      production of antigen-specific IgG1 but not other isotypes upon immunization of
      mice with the TI-2 model antigen (Ag) NIP-Ficoll. This effect was mediated by the
      binding of anti-CD83 to CD83 on the surface of B cells themselves. In the current
      study we show that administration of anti-CD83 enhances IgG1-production
      independent of IL-4. Application of anti-CD83 does not alter the proliferation
      and general expansion of NIP-specific B cells. In the presence of anti-CD83,
      immunized mice develop normal frequencies of plasmablasts in response to NIP
      Ficoll of which an increased number produces IgG1. These cells localize in
      extrafollicular foci in the spleen of immunized mice and originate from the
      marginal zone B cell pool. Taken together, our results indicate that CD83
      engagement in vivo does not generally enhance B cell activation but selectively
      promotes IgG1 class switch in marginal zone B cells in response to TI-2 Ag. 

PMID- 25766205
TI  - Synthetic magnetoelectric coupling in a nanocomposite multiferroic.
AB  - Given the paucity of single phase multiferroic materials (with large
      ferromagnetic moment), composite systems seem an attractive solution to realize
      magnetoelectric coupling between ferromagnetic and ferroelectric order
      parameters. Despite having antiferromagnetic order, BiFeO3 (BFO) has nevertheless
      been a key material due to excellent ferroelectric properties at room
      temperature. We studied a superlattice composed of 8 repetitions of 6 unit cells
      of La0.7Sr0.3MnO3 (LSMO) grown on 5 unit cells of BFO. Significant net
      uncompensated magnetization in BFO, an insulating superlattice, is demonstrated
      using polarized neutron reflectometry. Remarkably, the magnetization enables
      magnetic field to change the dielectric properties of the superlattice, which we
      cite as an example of synthetic magnetoelectric coupling. Importantly, controlled
      creation of magnetic moment in BFO is a much needed path toward design and
      implementation of integrated oxide devices for next generation magnetoelectric
      data storage platforms.

PMID- 25766206
TI  - Brain science and illness beliefs: an unexpected explanation of the healing power
      of therapeutic conversations and the family interventions that matter.
AB  - Paradigm families and paradigm practice moments have shown me that therapeutic
      conversations between nurses and families can profoundly and positively change
      illness beliefs in family members and nurses and contribute to healing from
      serious illness. The integration of brain science into nursing practice offers
      further understanding of the importance of illness beliefs and the role they may
      play in helping individual and family healing. Brain science offers explanations
      that connect how certain family nursing interventions that soften suffering and
      challenge constraining illness beliefs may result in changes in brain structure
      and functioning. New illness beliefs may result in new neural pathways in the
      brain, and therefore, possibilities for a new way of being in relationship with
      illness and in relationship with others can also develop. Newly acquired practice
      skills and interventions that have emerged from an understanding of brain science
      plus the reemphasis of other interventions utilized in the Illness Beliefs Model
      are offered to enhance our care of families suffering with illness. 

PMID- 25766207
TI  - Chemistry embraced by all.

PMID- 25766209
TI  - Particle Physics. Excitement, anxiety greet LHC restart.

PMID- 25766210
TI  - Atmospheric Science. California fogs are thinning.

PMID- 25766211
TI  - Archaeology. Militants leave trail of destruction at Iraqi sites.

PMID- 25766212
TI  - Neuroscience. Can sound open the brain for therapies?

PMID- 25766213
TI  - Virology. Bird flu virus's promiscuity raises red flags.

PMID- 25766214
TI  - Infectious Diseases. As Ebola fades, a new threat.

PMID- 25766215
TI  - The synthesis machine.

PMID- 25766216
TI  - Second sight.

PMID- 25766217
TI  - Chemistry. Toward substitution with no regrets.

PMID- 25766218
TI  - Physics. A walk across a quantum lattice.

PMID- 25766219
TI  - Immunology. Getting sepsis therapy right.

PMID- 25766220
TI  - Organometallic Chemistry. Catalysis by nickel in its high oxidation state.

PMID- 25766221
TI  - Oceans. How climate influences sea-floor topography.

PMID- 25766222
TI  - Environment and Development. Get the science right when paying for nature's
      services.

PMID- 25766223
TI  - Emergency response for marine diseases.

PMID- 25766224
TI  - Sparing grasslands: map misinterpreted.

PMID- 25766225
TI  - Sparing grasslands: FAO's active role.

PMID- 25766226
TI  - Design, synthesis, and carbon-heteroatom coupling reactions of organometallic
      nickel(IV) complexes.
AB  - Homogeneous nickel catalysis is used for the synthesis of pharmaceuticals,
      natural products, and polymers. These reactions generally proceed via nickel
      intermediates in the Ni(0), Ni(I), Ni(II), and/or Ni(III) oxidation states. In
      contrast, Ni(IV) intermediates are rarely accessible. We report herein the
      design, synthesis, and characterization of a series of organometallic Ni(IV)
      complexes, accessed by the reaction of Ni(II) precursors with the widely used
      oxidant S-(trifluoromethyl)dibenzothiophenium triflate. These Ni(IV) complexes
      undergo highly selective carbon(sp(3))-oxygen, carbon(sp(3))-nitrogen, and
      carbon(sp(3))-sulfur coupling reactions with exogenous nucleophiles. The observed
      reactivity has the potential for direct applications in the development of nickel
      catalyzed carbon-heteroatom coupling reactions. 

PMID- 25766229
TI  - Strongly correlated quantum walks in optical lattices.
AB  - Full control over the dynamics of interacting, indistinguishable quantum
      particles is an important prerequisite for the experimental study of strongly
      correlated quantum matter and the implementation of high-fidelity quantum
      information processing. We demonstrate such control over the quantum walk-the
      quantum mechanical analog of the classical random walk-in the regime where
      dynamics are dominated by interparticle interactions. Using interacting bosonic
      atoms in an optical lattice, we directly observed fundamental effects such as the
      emergence of correlations in two-particle quantum walks, as well as strongly
      correlated Bloch oscillations in tilted optical lattices. Our approach can be
      scaled to larger systems, greatly extending the class of problems accessible via
      quantum walks. 

PMID- 25766228
TI  - A young multilayered terrane of the northern Mare Imbrium revealed by Chang'E-3
      mission.
AB  - China's Chang'E-3 (CE-3) spacecraft touched down on the northern Mare Imbrium of
      the lunar nearside (340.49 degrees E, 44.12 degrees N), a region not directly
      sampled before. We report preliminary results with data from the CE-3 lander
      descent camera and from the Yutu rover's camera and penetrating radar. After the
      landing at a young 450-meter crater rim, the Yutu rover drove 114 meters on the
      ejecta blanket and photographed the rough surface and the excavated boulders. The
      boulder contains a substantial amount of crystals, which are most likely
      plagioclase and/or other mafic silicate mineral aggregates similar to terrestrial
      dolerite. The Lunar Penetrating Radar detection and integrated geological
      interpretation have identified more than nine subsurface layers, suggesting that
      this region has experienced complex geological processes since the Imbrian and is
      compositionally distinct from the Apollo and Luna landing sites. 

PMID- 25766227
TI  - Synthesis of many different types of organic small molecules using one automated
      process.
AB  - Small-molecule synthesis usually relies on procedures that are highly customized
      for each target. A broadly applicable automated process could greatly increase
      the accessibility of this class of compounds to enable investigations of their
      practical potential. Here we report the synthesis of 14 distinct classes of small
      molecules using the same fully automated process. This was achieved by
      strategically expanding the scope of a building block-based synthesis platform to
      include even C(sp3)-rich polycyclic natural product frameworks and discovering a
      catch-and-release chromatographic purification protocol applicable to all of the
      corresponding intermediates. With thousands of compatible building blocks already
      commercially available, many small molecules are now accessible with this
      platform. More broadly, these findings illuminate an actionable roadmap to a more
      general and automated approach for small-molecule synthesis.

PMID- 25766230
TI  - Coulomb crystallization of highly charged ions.
AB  - Control over the motional degrees of freedom of atoms, ions, and molecules in a
      field-free environment enables unrivalled measurement accuracies but has yet to
      be applied to highly charged ions (HCIs), which are of particular interest to
      future atomic clock designs and searches for physics beyond the Standard Model.
      Here, we report on the Coulomb crystallization of HCIs (specifically (40)Ar(13+))
      produced in an electron beam ion trap and retrapped in a cryogenic linear
      radiofrequency trap by means of sympathetic motional cooling through Coulomb
      interaction with a directly laser-cooled ensemble of Be(+) ions. We also
      demonstrate cooling of a single Ar(13+) ion by a single Be(+) ion-the
      prerequisite for quantum logic spectroscopy with a potential 10(-19) accuracy
      level. Achieving a seven-orders-of-magnitude decrease in HCI temperature starting
      at megakelvin down to the millikelvin range removes the major obstacle for HCI
      investigation with high-precision laser spectroscopy. 

PMID- 25766231
TI  - Glacial cycles drive variations in the production of oceanic crust.
AB  - Glacial cycles redistribute water between oceans and continents, causing pressure
      changes in the upper mantle, with consequences for the melting of Earth's
      interior. Using Plio-Pleistocene sea-level variations as a forcing function,
      theoretical models of mid-ocean ridge dynamics that include melt transport
      predict temporal variations in crustal thickness of hundreds of meters. New
      bathymetry from the Australian-Antarctic ridge shows statistically significant
      spectral energy near the Milankovitch periods of 23, 41, and 100 thousand years,
      which is consistent with model predictions. These results suggest that abyssal
      hills, one of the most common bathymetric features on Earth, record the magmatic
      response to changes in sea level. The models and data support a link between
      glacial cycles at the surface and mantle melting at depth, recorded in the
      bathymetric fabric of the sea floor. 

PMID- 25766232
TI  - Reduced vaccination and the risk of measles and other childhood infections post
      Ebola.
AB  - The Ebola epidemic in West Africa has caused substantial morbidity and mortality.
      The outbreak has also disrupted health care services, including childhood
      vaccinations, creating a second public health crisis. We project that after 6 to
      18 months of disruptions, a large connected cluster of children unvaccinated for
      measles will accumulate across Guinea, Liberia, and Sierra Leone. This pool of
      susceptibility increases the expected size of a regional measles outbreak from
      127,000 to 227,000 cases after 18 months, resulting in 2000 to 16,000 additional
      deaths (comparable to the numbers of Ebola deaths reported thus far). There is a
      clear path to avoiding outbreaks of childhood vaccine-preventable diseases once
      the threat of Ebola begins to recede: an aggressive regional vaccination campaign
      aimed at age groups left unprotected because of health care disruptions. 

PMID- 25766233
TI  - Conservatives report, but liberals display, greater happiness.
AB  - Research suggesting that political conservatives are happier than political
      liberals has relied exclusively on self-report measures of subjective well-being.
      We show that this finding is fully mediated by conservatives' self-enhancing
      style of self-report (study 1; N = 1433) and then describe three studies drawing
      from "big data" sources to assess liberal-conservative differences in happiness
      related behavior (studies 2 to 4; N = 4936). Relative to conservatives, liberals
      more frequently used positive emotional language in their speech and smiled more
      intensely and genuinely in photographs. Our results were consistent across large
      samples of online survey takers, U.S. politicians, Twitter users, and LinkedIn
      users. Our findings illustrate the nuanced relationship between political
      ideology, self-enhancement, and happiness and illuminate the contradictory ways
      that happiness differences can manifest across behavior and self-reports. 

PMID- 25766234
TI  - Direct evidence for human reliance on rainforest resources in late Pleistocene
      Sri Lanka.
AB  - Human occupation of tropical rainforest habitats is thought to be a mainly
      Holocene phenomenon. Although archaeological and paleoenvironmental data have
      hinted at pre-Holocene rainforest foraging, earlier human reliance on rainforest
      resources has not been shown directly. We applied stable carbon and oxygen
      isotope analysis to human and faunal tooth enamel from four late Pleistocene-to
      Holocene archaeological sites in Sri Lanka. The results show that human foragers
      relied primarily on rainforest resources from at least ~20,000 years ago, with a
      distinct preference for semi-open rainforest and rain forest edges. Homo sapiens'
      relationship with the tropical rainforests of South Asia is therefore long
      standing, a conclusion that indicates the time-depth of anthropogenic reliance
      and influence on these habitats. 

PMID- 25766235
TI  - Control of mammalian G protein signaling by N-terminal acetylation and the N-end
      rule pathway.
AB  - Rgs2, a regulator of G proteins, lowers blood pressure by decreasing signaling
      through Galphaq. Human patients expressing Met-Leu-Rgs2 (ML-Rgs2) or Met-Arg-Rgs2
      (MR-Rgs2) are hypertensive relative to people expressing wild-type Met-Gln-Rgs2
      (MQ-Rgs2). We found that wild-type MQ-Rgs2 and its mutant, MR-Rgs2, were
      destroyed by the Ac/N-end rule pathway, which recognizes N(alpha)-terminally
      acetylated (Nt-acetylated) proteins. The shortest-lived mutant, ML-Rgs2, was
      targeted by both the Ac/N-end rule and Arg/N-end rule pathways. The latter
      pathway recognizes unacetylated N-terminal residues. Thus, the Nt-acetylated Ac
      MX-Rgs2 (X = Arg, Gln, Leu) proteins are specific substrates of the mammalian
      Ac/N-end rule pathway. Furthermore, the Ac/N-degron of Ac-MQ-Rgs2 was
      conditional, and Teb4, an endoplasmic reticulum (ER) membrane-embedded ubiquitin
      ligase, was able to regulate G protein signaling by targeting Ac-MX-Rgs2 proteins
      for degradation through their N(alpha)-terminal acetyl group. 

PMID- 25766236
TI  - K2P channel gating mechanisms revealed by structures of TREK-2 and a complex with
      Prozac.
AB  - TREK-2 (KCNK10/K2P10), a two-pore domain potassium (K2P) channel, is gated by
      multiple stimuli such as stretch, fatty acids, and pH and by several drugs.
      However, the mechanisms that control channel gating are unclear. Here we present
      crystal structures of the human TREK-2 channel (up to 3.4 angstrom resolution) in
      two conformations and in complex with norfluoxetine, the active metabolite of
      fluoxetine (Prozac) and a state-dependent blocker of TREK channels. Norfluoxetine
      binds within intramembrane fenestrations found in only one of these two
      conformations. Channel activation by arachidonic acid and mechanical stretch
      involves conversion between these states through movement of the pore-lining
      helices. These results provide an explanation for TREK channel
      mechanosensitivity, regulation by diverse stimuli, and possible off-target
      effects of the serotonin reuptake inhibitor Prozac. 

PMID- 25766238
TI  - Time-restricted feeding attenuates age-related cardiac decline in Drosophila.
AB  - Circadian clocks orchestrate periods of rest or activity and feeding or fasting
      over the course of a 24-hour day and maintain homeostasis. To assess whether a
      consolidated 24-hour cycle of feeding and fasting can sustain health, we explored
      the effect of time-restricted feeding (TRF; food access limited to daytime 12
      hours every day) on neural, peripheral, and cardiovascular physiology in
      Drosophila melanogaster. We detected improved sleep, prevention of body weight
      gain, and deceleration of cardiac aging under TRF, even when caloric intake and
      activity were unchanged. We used temporal gene expression profiling and
      validation through classical genetics to identify the TCP-1 ring complex (TRiC)
      chaperonin, the mitochondrial electron transport chain complexes, and the
      circadian clock as pathways mediating the benefits of TRF. 

PMID- 25766237
TI  - Interleukin-3 amplifies acute inflammation and is a potential therapeutic target
      in sepsis.
AB  - Sepsis is a frequently fatal condition characterized by an uncontrolled and
      harmful host reaction to microbial infection. Despite the prevalence and severity
      of sepsis, we lack a fundamental grasp of its pathophysiology. Here we report
      that the cytokine interleukin-3 (IL-3) potentiates inflammation in sepsis. Using
      a mouse model of abdominal sepsis, we showed that innate response activator B
      cells produce IL-3, which induces myelopoiesis of Ly-6C(high) monocytes and
      neutrophils and fuels a cytokine storm. IL-3 deficiency protects mice against
      sepsis. In humans with sepsis, high plasma IL-3 levels are associated with high
      mortality even after adjusting for prognostic indicators. This study deepens our
      understanding of immune activation, identifies IL-3 as an orchestrator of
      emergency myelopoiesis, and reveals a new therapeutic target for treating sepsis.

PMID- 25766239
TI  - Into the wilderness.

PMID- 25766241
TI  - Studies for development of novel quinazolinones: new biomarker for EGFR.
AB  - The binding capabilities of a series of novel quinazolinone molecules were
      established and stated in a comprehensive computational methodology as well as by
      in vitro analysis. The main focus of this work was to achieve more insight of the
      interactions with crystal structure of PDB ID: 1M17 and predict their binding
      mode to EGFR. Three molecules were screened for further examination, which were
      synthesized and characterized using spectroscopic techniques. The persuasive
      affinity of these molecules towards EGFR inhibition (IC50 for QT=45nM) was
      established and validated from specific kinase assay including the cell viability
      spectrophotometric assay (QT=12nM). Drug likeliness property were also considered
      by analysing, the ADME of these molecules by using scintigraphic techniques. The
      result showed antitumour activity of QT (4.17 tumour/muscle at 4h). Further photo
      physical properties were also analysed to see in vitro HSA binding to QT. 

PMID- 25766242
TI  - Theoretical model to investigate the alkyl chain and anion dependent interactions
      of gemini surfactant with bovine serum albumin.
AB  - Surfactants are used to prevent the irreversible aggregation of partially
      refolded proteins and they also assist in protein refolding. We have reported the
      design and screening of gemini surfactant to stabilize bovine serum albumin (BSA)
      with the help of computational tool (iGEMDOCK). A series of gemini surfactant has
      been designed based on bis-N-alkyl nicotinate dianion via varying the alkyl group
      and anion. On changing the alkyl group and anion of the surfactant, the value of
      Log P changes means polarity of surfactant can be tuned. Further, the virtual
      screening of the gemini surfactant has been carried out based on generic
      evolutionary method. Herein, thermodynamic data was studied to determine the
      potential of gemini surfactant as BSA stabilizer. Computational tools help to
      find out the efficient gemini surfactant to stabilize the BSA rather than to use
      the surfactant randomly and directionless for the stabilization. It can be
      confirmed through the experimental techniques. Previously, researcher synthesized
      one of the designed and used gemini surfactant to stabilize the BSA and their
      interactions were confirmed through various techniques and computational docking.
      But herein, the authors find the most competent gemini surfactant to stabilize
      BSA using computational tools on the basis of energy score. Different from the
      single chain surfactant, the gemini surfactants exhibit much stronger
      electrostatic and hydrophobic interactions with the protein and are thus
      effective at much lower concentrations. Based on the present study, it is
      expected that gemini surfactants may prove useful in the protein stabilization
      operations and may thus be effectively employed to circumvent the problem of
      misfolding and aggregation. 

PMID- 25766243
TI  - [Comparison of droperidol and ondansetron prophylactic effect on subarachnoid
      morphine-induced pruritus].
AB  - BACKGROUND AND OBJECTIVES: The prophylactic effect of ondansetron on subarachnoid
      morphine-induced pruritus is controversial, while evidence suggests that
      droperidol prevents pruritus. The aim of this study is to compare the effects of
      droperidol and ondansetron on subarachnoid morphine-induced pruritus. METHODS:
      180 ASA I or II patients scheduled to undergo cesarean sections under
      subarachnoid anesthesia combined with morphine 0.2mg were randomized to receive,
      after the child's birth, metoclopramide 10mg (Group I - control), droperidol
      2.5mg (Group II) or ondansetron 8mg (Group III). Postoperatively, the patients
      were assessed for pruritus (absent, mild, moderate or severe) or other side
      effects by blinded investigators. Patients were also blinded to their group
      allocation. The tendency to present more severe forms of pruritus was compared
      between groups. NNT was also determined. RESULTS: Patients assigned to receive
      droperidol [Proportional odds ratio: 0.45 (95% confidence interval 0.23-0.88)]
      reported less pruritus than those who received metoclopramide. Ondansetron effect
      was similar to metoclopramide [Proportional odds ratio: 0.95 (95% confidence
      interval 0.49-1.83)]. The NNT for droperidol and ondansetron was 4.0 and 14.7,
      respectively. CONCLUSIONS: Ondansetron does not inhibit subarachnoid morphine
      induced pruritus.

PMID- 25766240
TI  - Modeling infectious disease dynamics in the complex landscape of global health.
AB  - Despite some notable successes in the control of infectious diseases,
      transmissible pathogens still pose an enormous threat to human and animal health.
      The ecological and evolutionary dynamics of infections play out on a wide range
      of interconnected temporal, organizational, and spatial scales, which span hours
      to months, cells to ecosystems, and local to global spread. Moreover, some
      pathogens are directly transmitted between individuals of a single species,
      whereas others circulate among multiple hosts, need arthropod vectors, or can
      survive in environmental reservoirs. Many factors, including increasing
      antimicrobial resistance, increased human connectivity and changeable human
      behavior, elevate prevention and control from matters of national policy to
      international challenge. In the face of this complexity, mathematical models
      offer valuable tools for synthesizing information to understand epidemiological
      patterns, and for developing quantitative evidence for decision-making in global
      health. 

PMID- 25766247
TI  - A modified dose calculation formalism for electronic brachytherapy sources.
AB  - PURPOSE: To propose a modification of the current dose calculation formalism
      introduced in the Task Group No. 43 Report (TG-43) to accommodate an air-kerma
      rate standard for electronic brachytherapy sources as an alternative to an air
      kerma strength standard. METHODS: Electronic brachytherapy sources are miniature
      x-ray tubes emitting low energies with high-dose-rates. The National Institute of
      Standards and Technology (NIST) has introduced a new primary air-kerma rate
      standard for one of these sources, in contrast to air-kerma strength. A
      modification of the TG-43 protocol for calculation of dose-rate distributions
      around electronic brachytherapy sources including sources in an applicator is
      presented. It cannot be assumed that the perturbations from sources in an
      applicator are negligible, and thus, the applicator is incorporated in the
      formalism. The modified protocol mimics the fundamental methodology of the
      original TG-43 formalism, but now incorporates the new NIST-traceable source
      strength metric of air-kerma rate at 50 cm and introduces a new subscript, i, to
      denote the presence of an applicator used in treatment delivery. Applications of
      electronic brachytherapy sources for surface brachytherapy are not addressed in
      this Technical Note since they are well documented in other publications.
      RESULTS: A modification of the AAPM TG-43 protocol has been developed to
      accommodate an air-kerma rate standard for electronic brachytherapy sources as an
      alternative to an air-kerma strength standard. CONCLUSIONS: The modified TG-43
      formalism allows dose calculations to be performed using a new NIST-traceable
      source strength metric and introduces the concept of applicator-specific
      formalism parameters denoted with subscript, i.

PMID- 25766250
TI  - Facile electrodeposition of reduced graphene oxide hydrogels for high-performance
      supercapacitors.
AB  - We report both a facile, scalable method to prepare reduced graphene oxide
      hydrogels through the electrodeposition of graphene oxide and its use as an
      electrode for high-performance supercapacitors. Such systems exhibited specific
      capacitances of 147 and 223 F g(-1) at a current density of 10 A g(-1) when using
      H2SO4 and H2SO4 + hydroquinone redox electrolytes, respectively. 

PMID- 25766248
TI  - DNA-templated in situ growth of AgNPs on SWNTs: a new approach for highly
      sensitive SERS assay of microRNA.
AB  - In this communication, we find that the single-walled carbon nanotubes (SWNTs)
      can demonstrate an excellent ssDNA concentration-dependent surface enhanced Raman
      scattering (SERS) effect after the decoration of DNA-templated in situ grown
      AgNPs on the surface. Inspired by this, the SWNT@AgNPs hybrid nanocomposite was
      employed to achieve microRNA detection which is also sensitive to crude
      extraction from human breast cancer cells and even patient tissues before and
      after chemotherapy. 

PMID- 25766244
TI  - cAMP-dependent activation of protein kinase A as a therapeutic target of skin
      hyperpigmentation by diphenylmethylene hydrazinecarbothioamide.
AB  - BACKGROUND AND PURPOSE: cAMP as a second messenger stimulates expression of
      microphthalmia-associated transcription factor (MITF) or the tyrosinase gene in
      UVB-induced skin pigmentation. Diphenylmethylene hydrazinecarbothioamide (QNT 3
      80) inhibits alpha-melanocyte-stimulating hormone (alpha-MSH)-induced melanin
      production in B16 murine melanoma cells but its molecular basis remains to be
      defined. Here, we investigated the mechanism underlying the amelioration of skin
      hyperpigmentation by QNT 3-80. EXPERIMENTAL APPROACH: We used melanocyte cultures
      with raised levels of cAMP and UVB-irradiated dorsal skin of guinea pigs for
      pigmentation assays. Immunoprecipitation, kemptide phosphorylation, fluorescence
      analysis and docking simulation were applied to elucidate a molecular mechanism
      of QNT 3-80. KEY RESULTS: QNT 3-80 inhibited melanin production in melanocyte
      cultures with elevated levels of cAMP, including those from human foreskin. This
      compound also ameliorated hyperpigmentation in vivo in UVB-irradiated dorsal skin
      of guinea pigs. As a mechanism, QNT 3-80 directly antagonized cAMP binding to the
      regulatory subunit of PKA, nullified the dissociation and activation of inactive
      PKA holoenzyme in melanocytes and fitted into the cAMP-binding site on the
      crystal structure of human PKA under the most energetically favourable
      simulation. QNT 3-80 consequently inhibited cAMP- or UVB-induced phosphorylation
      (activation) of cAMP-responsive element-binding protein in vitro and in vivo,
      thus down-regulating expression of genes for MITF or tyrosinase in the
      melanogenic process. CONCLUSIONS AND IMPLICATIONS: Our data suggested that QNT 3
      80 could contribute significantly to the treatment of skin disorders with
      hyperpigmented patches with the cAMP-binding site of PKA as its molecular target.

PMID- 25766251
TI  - Gonadotropin Therapy versus Laparoscopic Ovarian Drilling in Clomiphene Citrate
      Resistant Polycystic Ovary Syndrome Patients: A Retrospective Cost-Effectiveness
      Analysis.
AB  - BACKGROUND: Gonadotropin therapy and laparoscopic ovarian drilling (LOD) are
      treatment options for ovulation induction (OI) in clomiphene citrate (CC)
      resistant polycystic ovary syndrome (PCOS) patients. The current evidence of the
      cost-effectiveness of both treatments is scarce, conflicting and performed from
      different health-economic perspectives. METHODS: A retrospective health-economic
      evaluation was performed from a societal perspective in which human menopausal
      gonadotropin (hMG) therapy (n = 43) was compared with LOD (n = 35), followed by
      OI with CC and/or hMG if spontaneous ovulation did not occur within 2 months.
      Data were collected until the patients were pregnant, with a time limit of 6
      months after the onset of treatment. Outcomes were expressed as ongoing pregnancy
      rate and number of live-born children. RESULTS: The ongoing pregnancy rate was
      21/35 (60%) after LOD and 30/43 (69.8%) after hMG treatment (relative risk 0.85,
      95% CI 0.61-1.19). The societal cost per patient, up to an ongoing pregnancy, was
      significantly higher after LOD versus hMG treatment (adjusted mean difference EUR
      1,073, 95% CI 180-1,967). CONCLUSION: This economic evaluation based on real-life
      data shows that the societal cost up to an ongoing pregnancy is less after hMG
      treatment when compared with LOD surgery in CC-resistant PCOS patients.

PMID- 25766253
TI  - Nutritional problems and solutions for the modern health epidemic.

PMID- 25766252
TI  - Lipidomic-based investigation into the regulatory effect of Schisandrin B on
      palmitic acid level in non-alcoholic steatotic livers.
AB  - Schisandrin B (SchB) is one of the most abundant bioactive dibenzocyclooctadiene
      derivatives found in the fruit of Schisandra chinensis. Here, we investigated the
      potential therapeutic effects of SchB on non-alcoholic fatty-liver disease
      (NAFLD). In lipidomic study, ingenuity pathway analysis highlighted palmitate
      biosynthesis metabolic pathway in the liver samples of SchB-treated high-fat-diet
      fed mice. Further experiments showed that the SchB treatment reduced expression
      and activity of fatty acid synthase, expressions of hepatic mature sterol
      regulatory element binding protein-1 and tumor necrosis factor-alpha, and hepatic
      level of palmitic acid which is known to promote progression of steatosis to
      steatohepatitis. Furthermore, the treatment also reduced hepatic fibrosis,
      activated nuclear factor-erythroid-2-related factor-2 which is known to attenuate
      the progression of NASH-related fibrosis. Interestingly, in fasting mice, a
      single high-dose SchB induced transient lipolysis and increased the expressions
      of adipose triglyceride lipase and phospho-hormone sensitive lipase. The
      treatment also increased plasma cholesterol levels and 3-hydroxy-3-methylglutaryl
      CoA reductase activity, reduced the hepatic low-density-lipoprotein receptor
      expression in these mice. Our data not only suggest SchB is a potential
      therapeutic agent for NAFLD, but also provided important information for a safe
      consumption of SchB because SchB overdosed under fasting condition will have
      adverse effects on lipid metabolism. 

PMID- 25766255
TI  - FGF22 signaling regulates synapse formation during post-injury remodeling of the
      spinal cord.
AB  - The remodeling of axonal circuits after injury requires the formation of new
      synaptic contacts to enable functional recovery. Which molecular signals initiate
      such axonal and synaptic reorganisation in the adult central nervous system is
      currently unknown. Here, we identify FGF22 as a key regulator of circuit
      remodeling in the injured spinal cord. We show that FGF22 is produced by spinal
      relay neurons, while its main receptors FGFR1 and FGFR2 are expressed by cortical
      projection neurons. FGF22 deficiency or the targeted deletion of FGFR1 and FGFR2
      in the hindlimb motor cortex limits the formation of new synapses between
      corticospinal collaterals and relay neurons, delays their molecular maturation,
      and impedes functional recovery in a mouse model of spinal cord injury. These
      results establish FGF22 as a synaptogenic mediator in the adult nervous system
      and a crucial regulator of synapse formation and maturation during post-injury
      remodeling in the spinal cord. 

PMID- 25766257
TI  - New Mutations of the ID1 Gene in Acute Myeloid Leukemia Patients.
AB  - OBJECTIVES: Overexpression of the inhibitor of DNA binding 1 (ID1) protein is
      found in many types of cancer. In acute myeloid leukemia (AML), the expression of
      ID1 is induced by abnormal tyrosine kinases, such as FLT3 and BCR-ABL. High level
      expression of ID1 is associated with poor prognosis in young patients. We aimed
      to explore the ID1 mutation and its prognosis in AML patients. METHODS: Two
      hundred and sixty-three AML patients were included. Cytogenetic results and ID1
      mutation were compared. The ID1 gene was amplified by nested PCR, and the
      mutation was identified by direct sequencing. RESULTS: Four new ID1 mutations
      (G40C, A124G, A230G, A349G) were identified in the normal karyotype patients. The
      A349G mutation, located in the nuclear export signal domain of the ID1 protein,
      was predicted by the in silico method as a damaged protein. Meanwhile, another
      new mutation, A290G, found in cases with 11q23 deletion, corresponded to the
      amino acid 97 in the helix 1 position of the ID1 protein. It could interfere with
      the dimerization of ID1 and EST-1, leading to a disruption of cell proliferation.
      CONCLUSIONS: In this study, we found 5 mutations in 260 AML patients. ID1
      mutations were not commonly observed in AML. This may differ in other hematologic
      malignancies. Further studies in other types of hematologic malignancy will help
      to clarify the importance of ID1 mutations. (c) 2015 S. Karger AG, Basel.

PMID- 25766254
TI  - Application of biomaterials to advance induced pluripotent stem cell research and
      therapy.
AB  - Derived from any somatic cell type and possessing unlimited self-renewal and
      differentiation potential, induced pluripotent stem cells (iPSCs) are poised to
      revolutionize stem cell biology and regenerative medicine research, bringing
      unprecedented opportunities for treating debilitating human diseases. To overcome
      the limitations associated with safety, efficiency, and scalability of
      traditional iPSC derivation, expansion, and differentiation protocols,
      biomaterials have recently been considered. Beyond addressing these limitations,
      the integration of biomaterials with existing iPSC culture platforms could offer
      additional opportunities to better probe the biology and control the behavior of
      iPSCs or their progeny in vitro and in vivo. Herein, we discuss the impact of
      biomaterials on the iPSC field, from derivation to tissue regeneration and
      modeling. Although still exploratory, we envision the emerging combination of
      biomaterials and iPSCs will be critical in the successful application of iPSCs
      and their progeny for research and clinical translation. 

PMID- 25766256
TI  - Prevalence of EGFR mutations in newly diagnosed locally advanced or metastatic
      non-small cell lung cancer Spanish patients and its association with histological
      subtypes and clinical features: The Spanish REASON study.
AB  - BACKGROUND AND OBJECTIVES: The aim of the REASON study is to determine the
      frequency of EGFR mutation in advanced non-small cell lung cancer (aNSCLC)
      patients in Spain (all histologies), and to better understand the clinical
      factors (gender, smoking habits and histological subtypes) that may be associated
      with EGFR mutations, in an unselected sample of aNSCLC patients. METHODS: All
      newly diagnosed aNSCLC patients from 40 selected centers in Spain were
      prospectively included for a 6-month period. Patient characteristics were
      obtained from clinical records. Mutation testing was performed on available tumor
      samples. Exploratory analyses were performed to characterize the clinico
      pathological factors associated with presence of EGFR mutations. RESULTS: From
      March 2010 to March 2011, 1113 patients were included in the study, of which 1009
      patients provided sample for EGFR mutation analysis (90.7%). Mutation analysis
      was not feasible in 146/1113 patients (13.1%) due to either sample unavailability
      (79/1113; 7.1%) or sample inadequacy (67/1113; 6.0%). Twenty-five out of 1113
      patients (2.3%) were excluded due to unavailable information. Most patients
      (99.5%) were Caucasian, 74.5% were male, and predominantly were current (38.1%)
      or former smokers (44.0%). Median age was 66 years (range 25-90) and 70.7% of
      patients had non-squamous histology (57.8% adenocarcinoma, 1.8% bronchoalveolar,
      11.1% large-cell carcinoma). Exon 19 deletions and the exon 21 L858R point
      mutation were analyzed in 942/1009 (93.4%) samples. Mutation rate was 11.6%
      (82.6% exon 19 dels and 17.4% L858R). To be never smoker (38.1%), female (25.4%),
      with bronchioloalveolar carcinoma (22.2%) or adenocarcinoma (15.4%) histology was
      associated with a higher prevalence of EGFR mutations. Exons 18, 20 and 21
      (excluding L858R) were analyzed in 505/942 samples, and EGFR mutations were found
      in 22/505 samples (4.4%). CONCLUSION: The estimated prevalence of sensitizing
      EGFR mutations (exon 19 del, exon 21 L858R) in an unselected samples of newly
      diagnosed aNSCLC patients in Spain (all histologies) is consistent with previous
      published data in Caucasian patients. When a sample is available, EGFR mutation
      testing is feasible in over 90% of cases, and may therefore be suitable for
      routine clinical practice. CLINICALTRIALS. GOV IDENTIFIER: NCT01081496.

PMID- 25766258
TI  - Effect of platelet-derived growth factor-B on renal cell carcinoma growth and
      progression.
AB  - BACKGROUND: Platelet-derived growth factor-B (PDGF-B) expression promotes the
      proliferation of mural cells surrounding the blood vessels during angiogenesis.
      The effect of PDGF-B involved in angiogenesis on tumor growth and progression in
      clear cell renal cell carcinoma (ccRCC) is unknown. METHODS: We examined the
      expression of PDGF-B and its receptor PDGFR-beta in 174 patients with ccRCC by
      microarray analysis. Cancer-specific survival was estimated using the Kaplan
      Meier method. PDGF-B-transfected and mock-transfected ACHN cells were implanted
      into mice to induce tumor formation and tumor growth, respectively, and
      progression in mice models was assessed using immunohistochemistry and
      histomorphology. The role of PDGF-B during angiogenesis in vitro was evaluated by
      flow cytometry analysis, cell migration, and tube formation assay. RESULTS: High
      expression of PDGF-B was associated with significantly decreased risk of cancer
      specific mortality (P <= 0.001). The data indicated significant inhibition of
      tumor growth (P <= 0.05) and a reduction in proliferating tumor cells (P = 0.019)
      in vivo. PDGF-B also inhibits tumor metastasis and invasion events in tumor
      bearing mice models. In vitro studies revealed that the tube formation capability
      of vascular smooth muscle cells (VSMCs), which are believed to be the precursors
      to pericytes in vivo, significantly induced by PDGF-B. The PDGF-B overexpression
      also results in a tendency to reside in S and G2/M phases of the cell cycle (P =
      0.001) and increasing migration capability of VSMCs (P <= 0.001). CONCLUSION: Our
      results demonstrated that PDGF-B, which increased VSMCs proliferation and
      migration capability during angiogenesis, limited tumor growth and progression in
      ccRCC. Therefore, PDGF-B may be a novel and promising prognostic marker.

PMID- 25766259
TI  - Formation of an imino-stabilized cyclic tin(II) cation from an
      amino(imino)stannylene.
AB  - The novel amino(imino)stannylene 1 was prepared by conversion of HNIPr (NIPr =
      bis(2,6-diisopropylphenyl)imidazolin-2-imino) with one equivalent of Lappert's
      tin reagent (Sn[N(SiMe3)2]2). Treatment of 1 with DMAP (4-dimethylaminopyridine)
      yields its Lewis acid-base adduct 2. The reaction of 1 with one equivalent of
      trimethylsilyl azide results in replacement of the amino group at the tin center
      by an N3 substituent with concomitant elimination of N(SiMe3)3 to afford dimeric
      [N3SnNIPr]2 (3). Remarkably, the reaction of 1 with B(C6F5)3 produces the novel
      tin(II) monocation 4(+)[MeB(C6F5)3](-) comprising a four-membered stannacycle
      through methyl-abstraction from the trimethylsilyl group.

PMID- 25766260
TI  - Preliminary study on dermoscopic features of vulvar lichen planus: new insights
      for diagnosis.

PMID- 25766261
TI  - The Benefit of a Glucose-Sparing PD Therapy on Glycemic Control Measured by Serum
      Fructosamine in Diabetic Patients in a Randomized, Controlled Trial (IMPENDIA).
AB  - BACKGROUND/AIMS: Poor glycemic control can lead to increased morbidity and
      mortality in peritoneal dialysis (PD) patients. Serum fructosamine may be a more
      reliable marker of glycemic control than HbA1c in dialysis patients. METHODS: We
      evaluated the effects of a glucose-sparing PD regimen on serum fructosamine. In
      the multicenter, controlled IMPENDIA trial, eligible diabetic PD patients were
      randomized (1:1) to a 24-hour combination of a glucose sparing regimen (n = 89)
      or a glucose-based therapy (n = 91). Serum fructosamine and HbA1c were measured
      at baseline, 3 months and 6 months; fructosamine measurements were corrected for
      serum albumin (AlbF). RESULTS: Serum fructosamine decreased from 297 to 253
      umol/l in the glucose-sparing group (95% confidence interval [CI] for the
      difference, -26 to -68, p < 0.001), and increased from 311 to 314 umol/l in the
      glucose-only group (95% CI for the difference, -23 to +19, p = 0.87). The mean
      difference in change of fructosamine levels between groups at 6 months was 64
      umol/l (95% CI 29-99, p < 0.001). HbA1c decreased versus baseline in both groups
      (treatment difference 0.3%, p = 0.07). The correlation between AlbF and baseline
      fasting serum glucose was stronger than that seen between HbA1c and baseline
      fasting serum glucose (r = 0.47, p < 0.0001 and r = 0.31, p < 0.0001,
      respectively). CONCLUSION: A glucose-sparing regimen (P-E-N) improved glycemic
      control as measured by serum fructosamine. Further studies are needed to
      establish fructosamine targets that will reduce the morbidity risk related to
      hyperglycemia in PD patients.

PMID- 25766263
TI  - Diminished P300 to physical risk in sensation seeking.
AB  - Zuckerman's theory proposes individual differences in optimal arousal and
      arousability level as the root of the sensation-seeking trait. The current study
      addressed how sensation seeking influences responses to emotional arousal at the
      electrophysiological level during a passive viewing task and at the
      psychometrical level during a self-assessment task. Electrophysiologically, high
      sensation seekers (HSSs) compared to low sensation seekers (LSSs) exhibited a
      reduced P300 for high-arousing stimuli (adventure and surreal pictures), but not
      for low-arousing stimuli (leisure and neutral pictures). Psychometrically, HSSs
      displayed a higher preference for adventure and surreal pictures whereas LSSs
      showed a higher preference for leisure pictures. Instead of supporting the
      optimal arousal hypothesis, these findings suggest that sensation seeking is
      associated with diminished P300 to physical risk, which may be driven by a
      hypoactive avoidance system in sensation seeking.

PMID- 25766262
TI  - Cortisol secretion and change in sleep problems in early childhood: Moderation by
      maternal overcontrol.
AB  - Childhood sleep problems are prevalent and relate to a wide range of negative
      psychological outcomes. However, it remains unclear how biological processes,
      such as HPA activity, may predict sleep problems over time in childhood in the
      context of certain parenting environments. Fifty-one mothers and their 18-20
      month-old toddlers participated in a short-term longitudinal study assessing how
      shared variance among morning levels, diurnal change, and nocturnal change in
      toddlers' cortisol secretion predicted change in sleep problems in the context of
      maternal overprotection and critical control. A composite characterized by low
      variability in, and, to a lesser extent, high morning values of cortisol,
      predicted increasing sleep problems from age 2 to age 3 when mothers reported
      high critical control. Results suggest value in assessing shared variance among
      different indices of cortisol secretion patterns and the interaction between
      cortisol and the environment in predicting sleep problems in early childhood.

PMID- 25766264
TI  - Sensory gating in adult with attention-deficit/hyperactivity disorder: Event
      evoked potential and perceptual experience reports comparisons with
      schizophrenia.
AB  - BACKGROUND: In daily life, adults with attention-deficit/hyperactivity disorder
      (ADHD) report abnormal perceptual experiences that can be related to sensory
      gating deficit. This study investigated and compared P50 suppression (a
      neurophysiological measure of sensory gating) and perceptual abnormalities
      related to sensory gating deficit in ADHD and schizophrenias patients. METHODS:
      Three groups were compared: 24 adults with ADHD, 24 patients with schizophrenia
      and 24 healthy subjects. The Sensory Gating Inventory (SGI), a validated self
      report questionnaire, was used to measure perceptual abnormalities related to
      sensory gating deficit. P50 suppression was measured by P50 amplitude changes in
      a dual-click conditioning-testing auditory event-related potential procedure.
      RESULTS: Adults with ADHD had significantly higher scores on the SGI and
      significantly lower P50 suppression than healthy subjects. These deficits were
      similar to those found in patients with schizophrenia. A correlation was found
      between both the SGI and P50 suppression data in adults with ADHD and patients
      with schizophrenia. DISCUSSION: The findings confirm previous results found in
      patients with schizophrenia. Moreover, adults with ADHD, similar to patients with
      schizophrenia, had abnormal P50 suppression and reported being flooded with
      sensory stimuli. Abnormal neurophysiologic responses to repetitive stimuli gave
      rise to clinically abnormal perceptions.

PMID- 25766265
TI  - Strategies for continuing professional development among younger, middle-aged,
      and older nurses: a biographical approach.
AB  - BACKGROUND: A nursing career can last for more than 40 years, during which
      continuing professional development is essential. Nurses participate in a variety
      of learning activities that correspond with their developmental motives. Lifespan
      psychology shows that work-related motives change with age, leading to the
      expectation that motives for continuing professional development also change.
      Nevertheless, little is known about nurses' continuing professional development
      strategies in different age groups. OBJECTIVES: To explore continuing
      professional development strategies among younger, middle-aged, and older nurses.
      METHODS: A qualitative study using semi-structured interviews, from a
      biographical perspective. Data were analysed using a vertical process aimed at
      creating individual learning biographies, and a horizontal process directed at
      discovering differences and similarities between age groups. PARTICIPANTS: Twenty
      one nurses in three age groups from general and academic hospitals in the
      Netherlands. RESULTS: In all age groups, daily work was an important trigger for
      professional development on the ward. Performing extra or new tasks appeared to
      be an additional trigger for undertaking learning activities external to the
      ward. Learning experiences in nurses' private lives also contributed to their
      continuing professional development. Besides these similarities, the data
      revealed differences in career stages and private lives, which appeared to be
      related to differences in continuing professional development strategy; 'gaining
      experience and building a career' held particularly true among younger nurses,
      'work-life balance' and 'keeping work interesting and varied' to middle-aged
      nurses, and 'consistency at work' to older nurses. CONCLUSIONS: Professional
      development strategies can aim at performing daily patient care, extra tasks and
      other roles. Age differences in these strategies appear to relate to tenure,
      perspectives on the future, and situations at home. These insights could help
      hospitals to orientate continuing professional development approaches toward the
      needs of all age groups. This should be particularly relevant in the face of
      present demographic changes in the nursing workforce.

PMID- 25766266
TI  - Professional integration as a process of professional resocialization:
      internationally educated health professionals in Canada.
AB  - This paper examines the process of professional resocialization among
      internationally educated health care professionals (IEHPs) in Canada. Analyzing
      data from qualitative interviews with 179 internationally educated physicians,
      nurses, and midwives and 70 federal, provincial and regional stakeholders
      involved in integration of IEHPs, we examine (1) which aspects of professional
      work are modified in transition to a new health care system; (2) which aspects of
      professional practice are learned by IEHPs in the new health environment, and (3)
      how IEHPs maintain their professional identity in transition to a new health care
      system. In doing so, we compare the accounts of IEHPs with the policy
      stakeholders' positions and analyze the similarities and the differences across
      three health care professions (medicine, nursing, and midwifery). This enables us
      to explore the issue of professional resocialization from the analytical
      intersection of gender, professional dominance, and institutional/organizational
      lenses. 

PMID- 25766267
TI  - Abnormal functional connectivity of EEG gamma band in patients with depression
      during emotional face processing.
AB  - OBJECTIVE: This paper evaluates the large-scale structure of functional brain
      networks using graph theoretical concepts and investigates the difference in
      brain functional networks between patients with depression and healthy controls
      while they were processing emotional stimuli. METHODS: Electroencephalography
      (EEG) activities were recorded from 16 patients with depression and 14 healthy
      controls when they performed a spatial search task for facial expressions.
      Correlations between all possible pairs of 59 electrodes were determined by
      coherence, and the coherence matrices were calculated in delta, theta, alpha,
      beta, and gamma bands (low gamma: 30-50Hz and high gamma: 50-80Hz, respectively).
      Graph theoretical analysis was applied to these matrices by using two indexes:
      the clustering coefficient and the characteristic path length. RESULTS: The
      global EEG coherence of patients with depression was significantly higher than
      that of healthy controls in both gamma bands, especially in the high gamma band.
      The global coherence in both gamma bands from healthy controls appeared higher in
      negative conditions than in positive conditions. All the brain networks were
      found to hold a regular and ordered topology during emotion processing. However,
      the brain network of patients with depression appeared randomized compared with
      the normal one. The abnormal network topology of patients with depression was
      detected in both the prefrontal and occipital regions. The negative bias from
      healthy controls occurred in both gamma bands during emotion processing, while it
      disappeared in patients with depression. CONCLUSIONS: The proposed work studied
      abnormally increased connectivity of brain functional networks in patients with
      depression. By combing the clustering coefficient and the characteristic path
      length, we found that the brain networks of patients with depression and healthy
      controls had regular networks during emotion processing. Yet the brain networks
      of the depressed group presented randomization trends. Moreover, negative bias
      was detected in the healthy controls during emotion processing, while it was not
      detected in patients with depression, which might be related to the types of
      negative stimuli used in this study. SIGNIFICANCE: The brain networks from both
      patients with depression and healthy controls were found to hold a regular and
      ordered topology. Yet the brain networks of patients with depression had
      randomization trends.

PMID- 25766268
TI  - Use of flexor carpi radialis turnover in fasciotomy defects.

PMID- 25766269
TI  - Brief culturally adapted CBT (CaCBT) for depression: a randomized controlled
      trial from Pakistan.
AB  - OBJECTIVES: To determine the efficacy of brief Culturally adapted CBT (CaCBT) for
      depression when added to Treatment As usual (TAU)-delivered by trained therapists
      using a manual compared with alone TAU. METHODS: This was an assessor-blinded,
      randomised controlled clinical trial. Particpants with a diagnosis of depression,
      attending psychiatry departments of three teaching hospitals in Lahore, Pakistan,
      were included in the study. We screened a total of 280 patients and randomly
      allocated 137 of them to CaCBT plus Treatment As Usual (TAU) [Treatment group] or
      to TAU alone [Control group]. Assessments were completed at baseline, at 3 months
      and at 9 months after baseline. Reduction in depression score (Hospital Anxiety
      and Depression-Depression Subscale) at 3 months was primary outcome measure. The
      secondary outcome measures included anxiety scores (Hospital Anxiety and
      Depression-Anxiety Subscale), somatic symptoms (Bradford Somatic Inventory),
      disability (Brief Disability Questionnaire) and satisfaction with the treatment.
      FINDINGS: A total of 69 participants were randomised to Treatment group and 68 to
      Control group. Participants in Treatment group showed statistically significant
      improvement in depression (p=0.000), anxiety (p=0.000), somatic symptoms
      (p=0.005) and disability (p=0.000). This effect was sustained at 9 months after
      baseline (Except for disability). Participants in Treatment group also reported
      higher satisfaction with treatment compared with those in Control group.
      CONCLUSION: Brief CaCBT can be effective in improving depressive symptoms, when
      compared with treatment as usual. This is the first report of a trial of
      Culturally adapted CBT from South Asia and further studies are needed to
      generalise these findings.

PMID- 25766270
TI  - Association of the COMT synonymous polymorphism Leu136Leu and missense variant
      Val158Met with mood disorders.
AB  - BACKGROUND: Major depressive disorder (MDD) and bipolar disorder (BD) are the two
      most common mood disorders. Given the recognized involvement of catecholamines in
      depression, genetic research focused on the evaluation of polymorphisms in genes
      coding for proteins that regulate neurotransmitter release, transport and
      degradation. Here we aimed at evaluating the distribution of two genetic variants
      of catechol-O-methyltransferase (COMT), namely the well characterized missense
      polymorphism G1947A (Val158Met) and the recently reported synonymous polymorphism
      C1886G (Leu136Leu), in MDD and BD patients compared with healthy subjects.
      METHODS: Genotyping for COMT polymorphisms was carried out by DNA direct
      sequencing in 112 patients (54 MDD and 58 BD) and 58 healthy subjects. RESULTS:
      We did not find significant differences in the Val158Met variant distribution
      between patients and controls. Instead, we found that the C1886 major allele and
      the CC1886 wild-type genotype frequencies were significantly higher in controls
      than in both groups of patients. On the contrary, the G1886 minor allele and the
      heterozygous CG1886 genotype were significantly more present in both MDD and BD
      patients than in healthy subjects. When looking at combined polymorphisms, we
      found a significantly higher frequency of the double heterozygous diplotype
      CG/GAVal/Met158 in both MDD and BD patients than in controls. Instead, the
      diplotype CC/GAVal/Met158 showed a significantly higher frequency in controls
      than in BD patients. LIMITATIONS: The small size of our study cohort may limit
      the generalizability of the present findings. CONCLUSIONS: This work first showed
      the association of combined Leu136Leu and Val158Met variants of COMT gene with
      MDD and BD.

PMID- 25766271
TI  - Biocompatibility of calcium phosphate bone cement with optimized mechanical
      properties.
AB  - The broad aim of this work was to investigate and optimize the properties of
      calcium phosphate bone cements (CPCs) for use in vertebroplasty to achieve
      effective primary fixation of spinal fractures. The incorporation of collagen,
      both bovine and from a marine sponge (Chondrosia reniformis), into a CPC was
      investigated. The biological properties of the CPC and collagen-CPC composites
      were assessed in vitro through the use of human bone marrow stromal cells.
      Cytotoxicity, proliferation, and osteoblastic differentiation were evaluated
      using lactate dehydrogenase, PicoGreen, and alkaline phosphatase activity assays,
      respectively. The addition of both types of collagen resulted in an increase in
      cytotoxicity, albeit not to a clinically relevant level. Cellular proliferation
      after 1, 7, and 14 days was unchanged. The osteogenic potential of the CPC was
      reduced through the addition of bovine collagen but remained unchanged in the
      case of the marine collagen. These findings, coupled with previous work showing
      that incorporation of marine collagen in this way can improve the physical
      properties of CPCs, suggest that such a composite may offer an alternative to
      CPCs in applications where low setting times and higher mechanical stability are
      important.

PMID- 25766272
TI  - Process parameter dependent growth phenomena of naproxen nanosuspension
      manufactured by wet media milling.
AB  - The production of nanosuspensions has proved to be an effective method for
      overcoming bioavailability challenges of poorly water soluble drugs. Wet milling
      in stirred media mills and planetary ball mills has become an established top
      down-method for producing such drug nanosuspensions. The quality of the resulting
      nanosuspension is determined by the stability against agglomeration on the one
      hand, and the process parameters of the mill on the other hand. In order to
      understand the occurring dependencies, a detailed screening study, not only on
      adequate stabilizers, but also on their optimum concentration was carried out for
      the active pharmaceutical ingredient (API) naproxen in a planetary ball mill. The
      type and concentration of the stabilizer had a pronounced influence on the
      minimum particle size obtained. With the best formulation the influence of the
      relevant process parameters on product quality was investigated to determine the
      grinding limit of naproxen. Besides the well known phenomenon of particle
      agglomeration, actual naproxen crystal growth and morphology alterations occurred
      during the process which has not been observed before. It was shown that, by
      adjusting the process parameters, those effects could be reduced or eliminated.
      Thus, besides real grinding and agglomeration a process parameter dependent
      ripening of the naproxen particles was identified to be a concurrent effect
      during the naproxen fine grinding process. 

PMID- 25766273
TI  - Increase in maternal death-related venous thromboembolism during pregnancy in
      Japan (2010-2013).
AB  - BACKGROUND: The aim of the present work was to understand the current
      circumstances of maternal-death-related venous thromboembolism (MD-VTE) in Japan.
      We retrospectively investigated the characteristics of cases of MD-VTE, and
      compared past and present rates of occurrence. METHODS AND RESULTS: We examined
      the Japanese data for MD-VTE in 2010-2013, and compared it with that from 1991
      1992. MD-VTE occurred in 17 women in 1991-1992, and in 13 women in 2010-2013. The
      maternal mortality ratio of MD-VTE was 0.7 per 100,000 in 1991-1992 and 0.4 per
      100,000 in 2010-2013. Both the maternal mortality ratio and rate of MD-VTE in
      2010-2013 deceased significantly compared with 1991-1992 (P<0.05). However, the
      number of cases of MD-VTE during pregnancy was 6 among 13 women (41%) in 2010
      2013, but 1 in 17 women (6%) in 1991-1992, showing an increase (P<0.05). In the
      present study, cesarean delivery was more frequently associated with MD-VTE.
      CONCLUSIONS: MD-VTE overall has decreased within the past 20 years in Japan. But,
      MD-VTE during pregnancy in 2010-2013 increased relative to 1991-1992. Future
      guidelines for prevention of VTE may need to extend beyond the perioperative
      period to decrease the incidence of MD-VTE.

PMID- 25766275
TI  - Modulation of autoimmunity and atherosclerosis - common targets and promising
      translational approaches against disease.
AB  - Atherosclerosis is a chronic inflammatory disease of the arterial wall that is
      influenced by several risk factors, including hyperlipidemia and hypertension.
      Autoimmune diseases substantially increase the risk for cardiovascular disease
      (CVD). Although atherosclerotic CVD, such as myocardial and stroke, is much more
      prevalent than classical autoimmune conditions such as rheumatoid arthritis,
      psoriasis, and systemic lupus erythematosus, these types of pathology have many
      similarities, raising the possibility that therapies against autoimmune disease
      can have beneficial effects on CVD. Substantial clinical and experimental data
      support the potential for immunomodulatory approaches to combating both
      autoimmune and cardiovascular diseases, including classical immunosuppressants,
      anticytokine therapy, the targeting of T and B cells and their responses, and
      vaccination. In this review, we discuss experimental and clinical studies that
      have used immunomodulatory approaches to mitigate autoimmune reactions and
      examine their potential to prevent and treat atherosclerotic CVD.

PMID- 25766277
TI  - Nanoalloy electrocatalysis: simulating cyclic voltammetry from configurational
      thermodynamics with adsorbates.
AB  - We simulate the adsorption isotherms for alloyed nanoparticles (nanoalloys) with
      adsorbates to determine cyclic voltammetry (CV) during electrocatalysis. The
      effect of alloying on nanoparticle adsorption isotherms is provided by a hybrid
      ensemble Monte Carlo simulation that uses the cluster expansion method extended
      to non-exchangeable coupled lattices for nanoalloys with adsorbates. Exemplified
      here for the hydrogen evolution reaction, a 2-dimensional CV is mapped for Pd-Pt
      nanoalloys as a function of both electrochemical potential and the global Pt
      composition, and shows a highly non-linear alloying effect on CV. Detailed
      features in CV arise from the interplay among the H-adsorption in multiple sites
      that is closely correlated with alloy configurations, which are in turn affected
      by the H-coverage. The origins of specific features in CV curves are assigned.
      The method provides a more complete means to design nanoalloys for
      electrocatalysis. 

PMID- 25766274
TI  - Ninjurin1 is a novel factor to regulate angiogenesis through the function of
      pericytes.
AB  - BACKGROUND: Capillary pericytes (cPCs), the mural cells of microvessels, play an
      important role in the formation and maintenance of microvessels; however, little
      is known about the mechanisms of how cPCs regulate angiogenesis. To identify
      factors that modulate cPC function, genes whose levels were altered in cPCs
      during neovessel formation were identified through a microarray screen. METHODS
      AND RESULTS: Ninjurin1 (nerve injury-induced protein, Ninj1) was selected as a
      candidate factor for angiogenesis regulation. Ninj1 was expressed in capillary
      cells including endothelial cells (cECs) and was expressed at a higher level in
      cPCs. Hypoxia induced the gene expression of Ninj1 in addition of vascular
      endothelial growth factor (VEGF) in cPCs. When cPCs were co-incubated with a
      thoracic aorta in a three-dimensional Matrigel system, the length of the EC-tubes
      sprouting from the aorta was increased. Small interfering RNA-mediated
      downregulation of Ninj1 in cPCs enhanced these cPCs-mediated angiogenic effects,
      whereas overexpression of Ninj1 attenuated their effects. The production of
      angiogenic growth factors, such as VEGF and angiopoietin 1, by cPCs was enhanced
      by the downregulation of Ninj1, and reduced by the overexpression of Ninj1.
      CONCLUSIONS: Ninj1 is a novel regulator for the angiogenic effect of PCs.
      Specifically, Ninj1 negatively regulates the formation of neovessels, that is,
      the EC-tube, by reducing the trophic effects of cPCs.

PMID- 25766276
TI  - Potassium abnormalities in current clinical practice: frequency, causes, severity
      and management.
AB  - OBJECTIVE: We aimed to investigate the prevalence and etiology of potassium
      abnormalities (hypokalemia and hyperkalemia) and management approaches for
      hospitalized patients. SUBJECTS AND METHODS: Over a 4-month period, all
      hospitalized patients at Hacettepe University Medical Faculty Hospitals who
      underwent at least one measurement of serum potassium during hospitalization were
      included. Data on serum levels of electrolytes, demographic characteristics,
      cause(s) of hospitalization, medications, etiology of potassium abnormality and
      treatment approaches were obtained from the hospital records. RESULTS: Of the
      9,045 hospitalized patients, 1,265 (14.0%) had a serum potassium abnormality; 604
      (6.7%) patients had hypokalemia and 661 (7.30%) had hyperkalemia. In the
      hypokalemic patients, the most important reasons were gastrointestinal losses in
      555 (91.8%) patients and renal losses in 252 (41.7%) patients. The most frequent
      treatment strategies were correcting the underlying cause and replacing the
      potassium deficit. Of the 604 hypokalemic patients, 319 (52.8%) were normokalemic
      at hospital discharge. The most common reason for hyperkalemia was treatment with
      renin-angiotensin-aldosterone system blockers in 228 (34.4%) patients, followed
      by renal failure in 191 (28.8%). Two hundred and ninety-eight (45.0%) patients
      were followed without any specific treatment. Of the 661 hyperkalemic patients,
      324 (49.0%) were normokalemic at hospital discharge. CONCLUSION: This study
      showed a high prevalence of potassium imbalance among hospitalized patients.
      Although most of the potassium abnormalities were mild/moderate, approximately
      half of the patients treated for hypokalemia or hyperkalemia were discharged from
      the hospital with ongoing dyskalemia.

PMID- 25766278
TI  - Salicylic-acid elicited phospholipase D responses in Capsicum chinense cell
      cultures.
AB  - The plant response to different stress types can occur through stimulus
      recognition and the subsequent signal transduction through second messengers that
      send information to the regulation of metabolism and the expression of defense
      genes. The phospholipidic signaling pathway forms part of the plant response to
      several phytoregulators, such as salicylic acid (SA), which has been widely used
      to stimulate secondary metabolite production in cell cultures. In this work, we
      studied the effects of SA treatment on [(32)-P]Pi phospholipid turnover and
      phospholipase D (PLD) activity using cultured Capsicum chinense cells. In
      cultured cells, the PIP2 turnover showed changes after SA treatment, while the
      most abundant phospholipids (PLs), such as phosphatidylcholine (PC), did not show
      changes during the temporal course. SA treatment significantly increased
      phosphatidic acid (PA) turnover over time compared to control cells. The PA
      accumulation in cells treated with 1-butanol showed a decrease in messengers; at
      the same time, there was a 1.5-fold increase in phosphatidylbutanol. These
      results suggest that the participation of the PLD pathway is a source of PA
      production, and the activation of this mechanism may be important in the cell
      responses to SA treatment.

PMID- 25766279
TI  - Protective effect of botulinum toxin A after cutaneous ischemia-reperfusion
      injury.
AB  - Botulinum toxin A (BTX-A) blocks the release of acetylcholine vesicles into the
      synaptic space, and has been clinically used for aesthetic indications,
      neuromuscular disorders and hyperhidrosis. Several studies have demonstrated that
      BTX-A enhanced the blood flow and improved ischemia in animal models. Our
      objective was to assess the effects of BTX-A on cutaneous ischemia-reperfusion
      (I/R) injuries, mimicking decubitus ulcers. The administration of BTX-A in I/R
      areas significantly inhibited the formation of decubitus-like ulcer in cutaneous
      I/R injury mouse model. The number of CD31(+) vessels and alphaSMA(+) pericytes
      or myofibroblasts in wounds were significantly increased in the I/R mice treated
      with BTX-A. The hypoxic area and the number of oxidative stress-associated DNA
      damaged cells and apoptotic cells in the I/R sites were reduced by BTX-A
      administration. In an in vitro assay, BTX-A significantly prevented the oxidant
      induced intracellular accumulation of reactive oxygen species (ROS) in vascular
      endothelial cells. Furthermore, the administration of BTX-A completely suppressed
      the ulcer formation in an intermittent short-time cutaneous I/R injury model.
      These results suggest that BTX-A might have protective effects against ulcer
      formation after cutaneous I/R injury by enhancing angiogenesis and inhibiting
      hypoxia-induced cellular damage. Exogenous application of BTX-A might have
      therapeutic potential for cutaneous I/R injuries. 

PMID- 25766280
TI  - Regulation of microRNAs miR-30a and miR-143 in cerebral vasculature after
      experimental subarachnoid hemorrhage in rats.
AB  - BACKGROUND: microRNAs (miRNAs) are important regulators of translation and have
      been implicated in the pathogenesis of a number of cardiovascular diseases,
      including stroke, and suggested as possible prognostic biomarkers. Our aim was to
      identify miRNAs that are differentially regulated in cerebral arteries after
      subarachnoid hemorrhage (SAH), using a rat injection model of SAH and a qPCR
      based screen of 728 rat miRNAs. Additionally, serum was analyzed for a possible
      spill-over to the circulation of regulated miRNAs from the vessel walls. RESULTS:
      We identified 482 different miRNAs expressed in cerebral arteries post-SAH. Two
      miRNAs, miR-30a and miR-143, were significantly upregulated in cerebral arteries
      after SAH when compared to sham-operated animals. However, none of these
      exhibited significantly altered serum levels after SAH versus post-sham surgery.
      The most robust upregulation was seen for miR-143, which has several predicted
      targets and is a strong regulator of vascular morphology. We hypothesize that miR
      30a and miR-143 may play a role in the vascular wall changes seen after SAH.
      CONCLUSIONS: We report that miR-30a and miR-143 in the cerebral arteries show
      significant changes over time after SAH, but do not differ from sham-operated
      rats at 24 h post-SAH. Although this finding suggests interesting novel possible
      mechanisms involved in post-SAH cerebrovascular changes, the lack of regulation
      of these miRNAs in serum excludes their use as blood-borne biomarkers for
      cerebrovascular changes following SAH.

PMID- 25766281
TI  - The early stages of the immune response of the European abalone Haliotis
      tuberculata to a Vibrio harveyi infection.
AB  - Vibrio harveyi is a marine bacterial pathogen responsible for episodic abalone
      mortalities in France, Japan and Australia. In the European abalone, V. harveyi
      invades the circulatory system in a few hours after exposure and is lethal after
      2 days of infection. In this study, we investigated the responses of European
      abalone immune cells over the first 24 h of infection. Results revealed an
      initial induction of immune gene expression including Rel/NF-kB, Mpeg and
      Clathrin. It is rapidly followed by a significant immuno-suppression
      characterized by reduced cellular hemocyte parameters, immune response gene
      expressions and enzymatic activities. Interestingly, Ferritin was overexpressed
      after 24 h of infection suggesting that abalone attempt to counter V. harveyi
      infection using soluble effectors. Immune function alteration was positively
      correlated with V. harveyi concentration. This study provides the evidence that
      V. harveyi has a hemolytic activity and an immuno-suppressive effect in the
      European abalone. 

PMID- 25766282
TI  - Sequence analysis and characterisation of virally induced viperin in the
      saltwater crocodile (Crocodylus porosus).
AB  - A number of pathogens have been detected in crocodiles, however little is known
      about their ability to control these pathogens. The interferon stimulated gene
      (ISG), viperin, has gained attention recently as an important host protein
      involved in multiple arms of the immune response. Viperin in concert with a
      number of other ISGs was upregulated in response to viral nucleic acid mimics and
      sendai virus in the C. porosus cell line, LV-1, indicating an intact early innate
      response to viral infection in these animals for the first time. Viperin was
      cloned from the LV-1 cell line and shown to have similar localisation patterns as
      human viperin, as well as demonstrating extremely high conservation with the
      human orthologue, excepting at the N-terminus. Interestingly, C. porosus viperin
      was also able to inhibit Dengue virus replication in vitro, showing a high level
      of intact functionality for this protein across divergent animal species, and
      perhaps demonstrating its importance in the early innate response to pathogens in
      the animal kingdom. 

PMID- 25766283
TI  - A potential role for the midbrain in integrating fat-free mass determined energy
      needs: An H2 (15) O PET study.
AB  - Little is known on how sensing of energy needs is centrally represented,
      integrated, and translated into the behavioral aspects of energy homeostasis. Fat
      free mass (FFM) is the major determinant of energy expenditure. We investigated
      how interindividual variances in FFM relate to neuronal activity in humans.
      Healthy adults (n = 64, 21F/43M; age 31.3 +/- 9.1y; percentage of body fat [PFAT]
      25.6 +/- 10.7%; BMI 30.4 +/- 9) underwent a 36h fast and subsequent H(2) (15) O
      positron emission tomographic (PET) measurement of regional cerebral blood flow
      (rCBF). Multiple variable regression analysis revealed significant associations
      of FFM with rCBF within the midbrain [including parts of the periaqueductal gray
      (PAG), ventral tegmental area (VTA), thalamic and hypothalamic regions], the
      bilateral parahippocampal region, left anterior cingulate, left insular cortex,
      right cerebellum, and distinct regions within the temporal and occipital cortex.
      In contrast, no significant associations were found for fat mass (FM). We
      investigated the potential functional-anatomical link between FFM and central
      regulation of food intake by performing a conjunction analysis of FFM and the
      perceived hunger feelings. This showed a significant overlap within the midbrain
      PAG. Mediation analysis demonstrated a significant indirect effect of FFM on
      hunger with PAG rCBF as mediator. Most regions we found to be associated with FFM
      form part in ascending homeostatic pathways and cortical circuitries implicated
      in the regulation of basic bodily functions indicating a potential role of these
      central networks in the integration of FFM determined energy needs.

PMID- 25766285
TI  - Influenza surveillance: 2014-2015 H1N1 "swine"-derived influenza viruses from
      India.
AB  - The 2014-15 H1N1 outbreak in India has reportedly led to 800 fatalities. The
      reported influenza hemagglutinin sequences from India indicate that these viruses
      contain amino acid changes linked to enhanced virulence and are potentially
      antigenically distinct from the current vaccine containing 2009 (Cal0709) H1N1
      viral hemagglutinin. 

PMID- 25766284
TI  - Computational approaches to influenza surveillance: beyond timeliness.
AB  - Several digital data sources and systems have been advanced for use in augmenting
      traditional influenza surveillance systems. Although timeliness is one of the
      main advantages of these tools, there are several other recognizable uses and
      potential impact of these systems on the public and global public health. 

PMID- 25766286
TI  - A serpin takes a bite out of the flu.
AB  - Other than annual vaccinations, there are few remedies for seasonal influenza
      virus infections. A recent study in Cell from Dittmann et al. (2015) designed to
      reveal immune strategies against the flu has uncovered an Achilles' heel for
      influenza replication based on its requirement for host proteolytic machinery to
      enable efficient spread. 

PMID- 25766287
TI  - RIG-I works double duty.
AB  - The pathogen sensor RIG-I recognizes viral RNA and signals to induce an antiviral
      response. In this issue of Cell Host & Microbe, Weber et al. (2015), along with
      recent work by Sato et al. (2015), demonstrate that RIG-I directly inhibits viral
      replication independent of antiviral signaling.

PMID- 25766288
TI  - Caps off to poxviruses.
AB  - In this issue of Cell Host & Microbe, Liu et al. (2015) and Burgess and Mohr
      (2015) describe how two poxvirus mRNA decapping enzymes hijack a host 5'-to-3'
      exoribonuclease to evade antiviral innate immunity by limiting accumulation of
      double-stranded RNA. 

PMID- 25766289
TI  - Inflammasomes in aspergillosis--it takes two to tango.
AB  - Intracellular inflammasome complexes regulate critical cytokine responses to
      infections. In this issue of Cell Host & Microbe,Karki et al. (2015) show that
      protection against the fungus Aspergillus requires the combined efforts of the
      NLRP3 and AIM2 inflammasomes and involves both caspase-1 and caspase-8.

PMID- 25766290
TI  - H10N8 and H6N1 maintain avian receptor binding.
AB  - Influenza viruses of animals can cross species and infect humans. In this issue
      of Cell Host & Microbe, Zhang et al. (2015) and Tzarum et al. (2015) describe
      crystal structures and receptor-binding properties of hemagglutinins of avian
      origin H10N8 and H6N1 influenza viruses. Human infections with these viruses are
      not associated with a switch favoring human receptor binding.

PMID- 25766291
TI  - Influenza vaccines: challenges and solutions.
AB  - Vaccination is the best method for the prevention and control of influenza.
      Vaccination can reduce illness and lessen severity of infection. This review
      focuses on how currently licensed influenza vaccines are generated in the U.S.,
      why the biology of influenza poses vaccine challenges, and vaccine approaches on
      the horizon that address these challenges. 

PMID- 25766292
TI  - Predicting vaccine responsiveness.
AB  - Vaccination has saved many lives and prevented needless suffering from disease,
      but it is not always effective. Immune responses are a highly "personalized"
      aspect of an individual's biology, as they are subject to germline genetic
      influences but are embodied in cell populations that continuously sample the
      environment. Additionally, immunity is shaped by memory of prior infectious
      diseases and other antigenic exposures. Here, we review examples of recent
      technical advances and insights into human vaccine responses that are helping to
      define the features associated with successful vaccination and that may enable a
      more predictive vaccinology in the future. 

PMID- 25766293
TI  - Poxvirus decapping enzymes enhance virulence by preventing the accumulation of
      dsRNA and the induction of innate antiviral responses.
AB  - Poxvirus replication involves synthesis of double-stranded RNA (dsRNA), which can
      trigger antiviral responses by inducing phosphorylation-mediated activation of
      protein kinase R (PKR) and stimulating 2'5'-oligoadenylate synthetase (OAS). PKR
      inactivates the translation initiation factor eIF2alpha via phosphorylation,
      while OAS induces the endonuclease RNase L to degrade RNA. We show that poxvirus
      decapping enzymes D9 and D10, which remove caps from mRNAs, inhibit these
      antiviral responses by preventing dsRNA accumulation. Catalytic site mutations of
      D9 and D10, but not of either enzyme alone, halt vaccinia virus late protein
      synthesis and inhibit virus replication. Infection with the D9-D10 mutant was
      accompanied by massive mRNA reduction, cleavage of ribosomal RNA, and
      phosphorylation of PKR and eIF2alpha that correlated with a ~ 15-fold increase in
      dsRNA compared to wild-type virus. Additionally, mouse studies show extreme
      attenuation of the mutant virus. Thus, vaccinia virus decapping, in addition to
      targeting mRNAs for degradation, prevents dsRNA accumulation and anti-viral
      responses.

PMID- 25766294
TI  - Cellular 5'-3' mRNA exonuclease Xrn1 controls double-stranded RNA accumulation
      and anti-viral responses.
AB  - By accelerating global mRNA decay, many viruses impair host protein synthesis,
      limiting host defenses and stimulating virus mRNA translation. Vaccinia virus
      (VacV) encodes two decapping enzymes (D9, D10) that remove protective 5' caps on
      mRNAs, presumably generating substrates for degradation by the host exonuclease
      Xrn1. Surprisingly, we find VacV infection of Xrn1-depleted cells inhibits
      protein synthesis, compromising virus growth. These effects are aggravated by D9
      deficiency and dependent upon a virus transcription factor required for
      intermediate and late mRNA biogenesis. Considerable double-stranded RNA (dsRNA)
      accumulation in Xrn1-depleted cells is accompanied by activation of host dsRNA
      responsive defenses controlled by PKR and 2'-5' oligoadenylate synthetase (OAS),
      which respectively inactivate the translation initiation factor eIF2 and
      stimulate RNA cleavage by RNase L. This proceeds despite VacV-encoded PKR and
      RNase L antagonists being present. Moreover, Xrn1 depletion sensitizes uninfected
      cells to dsRNA treatment. Thus, Xrn1 is a cellular factor regulating dsRNA
      accumulation and dsRNA-responsive innate immune effectors.

PMID- 25766295
TI  - Structure and receptor binding of the hemagglutinin from a human H6N1 influenza
      virus.
AB  - Avian influenza viruses that cause infection and are transmissible in humans
      involve changes in the receptor binding site (RBS) of the viral hemagglutinin
      (HA) that alter receptor preference from alpha2-3-linked (avian-like) to alpha2-6
      linked (human-like) sialosides. A human case of avian-origin H6N1 influenza virus
      was recently reported, but the molecular mechanisms contributing to it crossing
      the species barrier are unknown. We find that, although the H6 HA RBS contains
      D190V and G228S substitutions that potentially promote human receptor binding,
      recombinant H6 HA preferentially binds alpha2-3-linked sialosides, indicating no
      adaptation to human receptors. Crystal structures of H6 HA with avian and human
      receptor analogs reveal that H6 HA preferentially interacts with avian receptor
      analogs. This binding mechanism differs from other HA subtypes due to a unique
      combination of RBS residues, highlighting additional variation in HA-receptor
      interactions and the challenges in predicting which influenza strains and
      subtypes can infect humans and cause pandemics.

PMID- 25766297
TI  - SnapShot: Evolution of human influenza A viruses.
AB  - The major natural hosts of influenza A viruses are wild aquatic birds.
      Occasionally, viruses are transmitted to mammalian and other avian species,
      including humans. Due to the high mutation rate and reassortment of the viral
      genome, the viruses may undergo adaptation to humans and then give rise to a
      pandemic. 

PMID- 25766296
TI  - A human-infecting H10N8 influenza virus retains a strong preference for avian
      type receptors.
AB  - Recent avian-origin H10N8 influenza A viruses that have infected humans pose a
      potential pandemic threat. Alterations in the viral surface glycoprotein,
      hemagglutinin (HA), typically are required for influenza A viruses to cross the
      species barrier for adaptation to a new host, but whether H10N8 contains
      adaptations supporting human infection remains incompletely understood. We
      investigated whether H10N8 HA can bind human receptors. Sialoside glycan
      microarray analysis showed that the H10 HA retains a strong preference for avian
      receptor analogs and negligible binding to human receptor analogs. Crystal
      structures of H10 HA with avian and human receptor analogs revealed the basis for
      preferential recognition of avian-like receptors. Furthermore, introduction of
      mutations into the H10 receptor-binding site (RBS) known to convert other HA
      subtypes from avian to human receptor specificity failed to switch preference to
      human receptors. Collectively, these findings suggest that the current H10N8
      human isolates are poorly adapted for efficient human-to-human transmission.

PMID- 25766298
TI  - Obituary: A/Prof John MacMillan (1959-2014).

PMID- 25766299
TI  - Changes in Gut Microbiota May Be Early Signs of Liver Toxicity Induced by
      Epoxiconazole in Rats.
AB  - OBJECTIVE: The gut microbiome is essential for human health due to its effects on
      disease development, drug metabolism and the immune system. It may also play a
      role in the interaction with environmental toxicants. However, the effect of
      epoxiconazole, a fungicide active ingredient from the class of azoles developed
      to protect crops, on the abundance and composition of the gut microbiome has
      never been studied. We put forward the hypothesis that changes in gut microbiota
      may be early signs of toxicity induced by epoxiconazole. METHODS: In this study,
      female rats were fed with epoxiconazole-adulterated diets (0, 4 and 100
      mg/kg/day) for 90 days. The gut microbiome was determined by 16S rRNA gene
      sequencing. Body and organ weight, and blood biochemistry were also measured
      after 90 days of oral epoxiconazole exposure. RESULTS: Interestingly, the
      abundance of gut Firmicutes decreased, and Bacteroidetes and Proteobacteria
      increased. At family level, Lachnospiraceae and Enterobacteriaceae were
      selectively enriched following epoxiconazole exposure. Our results indicate that
      epoxiconazole exposure may induce changes in the gut microbiome and potential
      liver toxicity. CONCLUSION: Changes in the gut microbiome may be used as early
      indicators for monitoring the health risk of the host.

PMID- 25766300
TI  - A Rabbit Model of Acanthamoeba Keratitis That Better Reflects the Natural Human
      Infection.
AB  - Acanthamoeba species are ubiquitous, free-living protozoa that can invade the
      cornea and result in Acanthamoeba keratitis (AK), a painful progressive sight
      threatening corneal disease. Disease progression in current animal models is too
      rapid to mimic AK in humans accurately. This study provides a novel method for
      establishing AK in rabbits and compared it with the conventional method with
      regard to pathogenesis and immune response in humans. The New Zealand white
      rabbits were randomly divided into two experimental groups (Groups A and B).
      Rabbits in the Group A (n = 14) received intrastromal injections of 1 * 10(4)
      /100 uL Acanthamoeba healyi trophozoites (conventional AK model). The Group B
      animals (n = 14) received microinjections of 1 * 10(4) /10 uL A. healyi
      trophozoites between the corneal epithelium and Bowman's layer, anterior to the
      corneal stroma (novel AK model). In addition, two rabbits were left untreated as
      normal controls. AK in the treated rabbits was evaluated clinically,
      histopathologically, and immunologically for 35 days. AK was successfully
      established in both the conventional and novel model groups. Compared with the
      Group A, AK in the Group B displayed an efficient immune response with less
      severe pathology. Moreover, the self-limiting but chronic nature of the infection
      in the Group B was strikingly similar to that of AK in humans. The novel animal
      model for AK described here more closely simulates the pathogenesis and immune
      response of Acanthamoeba corneal infection in humans than the animal models
      currently in use.

PMID- 25766301
TI  - Voltage attenuation of the electrocardiogram QRS complexes in a patient with
      "scorpion envenomation"-induced Takotsubo syndrome.

PMID- 25766302
TI  - Navigation surgery using an augmented reality for pancreatectomy.
AB  - AIM: The aim of this study was to evaluate the utility of navigation surgery
      using augmented reality technology (AR-based NS) for pancreatectomy. METHODS: The
      3D reconstructed images from CT were created by segmentation. The initial
      registration was performed by using the optical location sensor. The
      reconstructed images were superimposed onto the real organs in the monitor
      display. Of the 19 patients who had undergone hepatobiliary and pancreatic
      surgery using AR-based NS, the accuracy, visualization ability, and utility of
      our system were assessed in five cases with pancreatectomy. RESULTS: The position
      of each organ in the surface-rendering image corresponded almost to that of the
      actual organ. Reference to the display image allowed for safe dissection while
      preserving the adjacent vessels or organs. The locations of the lesions and
      resection line on the targeted organ were overlaid on the operating field. The
      initial mean registration error was improved to approximately 5 mm by our
      refinements. However, several problems such as registration accuracy, portability
      and cost still remain. CONCLUSION: AR-based NS contributed to accurate and
      effective surgical resection in pancreatectomy. The pancreas appears to be a
      suitable organ for further investigations. This technology is promising to
      improve surgical quality, training, and education.

PMID- 25766303
TI  - Serum omentin levels: A possible contribution to vascular involvement in patients
      with systemic sclerosis.
AB  - Adipokines have been shown to be potentially involved in various pathological
      processes of systemic sclerosis (SSc), including inflammation, vasculopathy and
      fibrosis, through their pleiotropic effects. Omentin is a member of the
      adipokines, and has a protective effect against vascular inflammation and
      pathological remodeling leading to atherosclerosis as well as a vasodilatory
      effect. To assess the potential role of omentin in the development of SSc, we
      determined serum omentin levels by enzyme-linked immunosorbent assay in 66 SSc
      and 21 control subjects and evaluated their clinical correlation. Serum omentin
      levels were significantly decreased in diffuse cutaneous SSc patients compared
      with limited cutaneous SSc patients, while comparable between total SSc patients
      and healthy controls. In diffuse cutaneous (dc)SSc, patients with a disease
      duration of 5 years or less had serum omentin levels significantly lower than
      those with a disease duration of more than 5 years. In total SSc, serum omentin
      levels were significantly higher in patients with elevated right ventricular
      systolic pressure than in the others, while serum omentin levels did not
      correlate with fibrotic and systemic inflammatory parameters. These results
      suggest that a loss of omentin-dependent protection against vascular inflammation
      and remodeling may be related to pathological vascular events of early dcSSc. The
      elevation of serum omentin levels may serve as a marker of vascular involvement
      leading to pulmonary arterial hypertension in SSc, which is possibly due to the
      compensatory induction of omentin against the increased pulmonary vascular tone. 

PMID- 25766304
TI  - Tuning the self-assembly of surfactants by the confinement of carbon nanotube
      arrays: a cornucopia of lamellar phase variants.
AB  - Tuning the self-assembly of building blocks to obtain a kaleidoscope of
      nanostructures is very important and challenging for the preparation of advanced
      nanomaterials. Amphiphiles confined within carbon nanotube (CNT) arrays can self
      assemble into complex structures that maintain the "bilayer" characteristic of a
      lamellar phase, we call them "lamellar phase variants (LPVs)". In this work, we
      carried out coarse-grained molecular dynamics (MD) studies to uncover novel LPVs.
      By varying the pattern of a CNT array, we obtained the "bilayer tube (BT)
      series", which contains circular, hexagonal, octagonal, and elliptical nanotubes.
      Furthermore, by introducing dislocation to CNT arrays, we obtained the "bilayer
      scroll (BS) series" that contains polymorphic nano-scrolls. These nanostructures
      are very novel and intriguing. To gain insights into the formation of LPVs, we
      studied the morphology evolution, which was demonstrated to be an unfamiliar
      "successive self-assembly process". These unusual self-assembling nanostructures
      and the formation process could provide clues for further studies on tuning the
      self-assembly of building blocks. The strategies developed in this work to obtain
      novel nanostructures are expected to facilitate the design and fabrication of
      nano-devices. 

PMID- 25766305
TI  - Predictive Risk Factors for Fear of Hypoglycemia and Anxiety-Related Emotional
      Disorders among Adolescents with Type 1 Diabetes.
AB  - OBJECTIVE: To explore the fear of hypoglycemia (FOH) and anxiety-related
      emotional disorders and their risk factors among adolescents with type 1 diabetes
      mellitus (T1DM). SUBJECTS AND METHODS: A cross-sectional study was conducted
      among 187 adolescents (aged 13-18 years; 92 males, 95 females) with T1DM at the
      Diabetes Treatment Center, Prince Sultan Military Medical City, Riyadh, Saudi
      Arabia, from June 2013 to February 2014. The participants were interviewed using
      FOH and Screen for Child Anxiety-Related Disorders (SCARED) scales. RESULTS:
      Females had significantly higher scores on all FOH and SCARED subscales compared
      to males. The mean scores for many subscales of FOH and SCARED were higher in the
      older age group (16-18 years), in those under multiple-dose injection (MDI)
      treatment (compared with the insulin pump treatment), and in those with a longer
      duration of T1DM. Similarly, significant differences were observed in those with
      high frequencies of hypoglycemia, passing out, hypoglycemia while asleep and
      awake, and hypoglycemia in front of friends and at school. Regression analysis
      revealed that higher age, female gender, MDI treatment, longer duration of T1DM,
      higher frequencies of hypoglycemia, passing out, hypoglycemia while asleep and
      awake, and hypoglycemia in front of friends and at school were the risk factors
      associated with the majority of the FOH and SCARED subscales. The behavior of the
      FOH subscale correlated with all the subscales of SCARED except the subscale of
      generalized anxiety disorder. Similarly, the FOH subscale of worry significantly
      correlated with all the subscales of SCARED. CONCLUSION: The strongest
      determinants of higher risk for the majority of the FOH and SCARED subscales were
      higher age, female gender, MDI treatment, longer duration of T1DM, higher
      frequency of hypoglycemia, passing out due to hypoglycemia, hypoglycemia while
      asleep and awake, and hypoglycemia in front of friends and at school.

PMID- 25766306
TI  - Investigation of the Occurrence of Porcine Reproductive and Respiratory Virus in
      Swine Herds Participating in an Area Regional Control and Elimination Project in
      Ontario, Canada.
AB  - The main goal of this study was to investigate the occurrence of porcine
      reproductive and respiratory syndrome virus (PRRSV)-specific genotypes in swine
      sites in Ontario (Canada) using molecular, spatial and network data from a
      porcine reproductive and respiratory syndrome (PRRS) regional control project.
      For each site, location, animal movement service provider (truck companies),
      PRRSV status and sequencing data of the open reading frame 5 (ORF5) were
      obtained. Three-kilometre buffers were created to evaluate neighbourhood
      characteristics for each site. Social network analysis was conducted on swine
      sites and trucking companies to assemble the network and define network
      components. Three different PRRSV genotypes were used as outcomes for statistical
      analysis based on the region's phylogenetic tree of the ORF5. Multivariable exact
      logistic regression was conducted to investigate the association between being
      positive for a specific genotype and two main exposures of interest: (i) having
      at least one neighbour within three km also positive for the same genotype
      outside the production system and (ii) having at least one positive site for the
      same genotype in the same truck network component outside the production system.
      Results showed that the importance of area spread and truck network on PRRSV
      occurrence differed according to genotype. Additionally, the Ontario PRRS
      database appears suitable for conducting regional disease investigations.
      Finally, the use of relatively new tools available for network, spatial and
      molecular analysis could be useful in investigation, control and prevention of
      endemic infectious diseases in animal populations.

PMID- 25766307
TI  - Unusually short chalcogen bonds involving organoselenium: insights into the Se-N
      bond cleavage mechanism of the antioxidant ebselen and analogues.
AB  - Structural studies on the polymorphs of the organoselenium antioxidant ebselen
      and its derivative show the potential of organic selenium to form unusually short
      Se???O chalcogen bonds that lead to conserved supramolecular recognition units.
      Se???O interactions observed in these polymorphs are the shortest such chalcogen
      bonds known for organoselenium compounds. The FTIR spectral evolution
      characteristics of this interaction from solution state to solid crystalline
      state further validates the robustness of this class of supramolecular
      recognition units. The strength and electronic nature of the Se???O chalcogen
      bonds were explored using high-resolution X-ray charge density analysis and atons
      in-molecules (AIM) theoretical analysis. A charge density study unravels the
      strong electrostatic nature of Se???O chalcogen bonding and soft-metal-like
      behavior of organoselenium. An analysis of the charge density around Se-N and Se
      C covalent bonds in conjunction with the Se???O chalcogen bonding modes in
      ebselen and its analogues provides insights into the mechanism of drug action in
      this class of organoselenium antioxidants. The potential role of the
      intermolecular Se???O chalcogen bonding in forming the intermediate
      supramolecular assembly that leads to the bond cleavage mechanism has been
      proposed in terms of electron density topological parameters in a series of
      molecular complexes of ebselen with reactive oxygen species (ROS).

PMID- 25766308
TI  - Genome-wide characterization of developmental stage- and tissue-specific
      transcription factors in wheat.
AB  - BACKGROUND: Wheat (Triticum aestivum) is one of the most important cereal crops,
      providing food for humans and feed for other animals. However, its productivity
      is challenged by various biotic and abiotic stresses such as fungal diseases,
      insects, drought, salinity, and cold. Transcription factors (TFs) regulate gene
      expression in different tissues and at various developmental stages in plants and
      animals, and they can be identified and classified into families according to
      their structural and specialized DNA-binding domains (DBDs). Transcription
      factors are important regulatory components of the genome, and are the main
      targets for engineering stress tolerance. RESULTS: In total, 2407 putative TFs
      were identified from wheat expressed sequence tags, and then classified into 63
      families by using Hmm searches against hidden Markov model (HMM) profiles. In
      this study, 2407 TFs represented approximately 2.22% of all genes in the wheat
      genome, a smaller proportion than those reported for other cereals in PlantTFDB
      V3.0 (3.33%-5.86%) and PlnTFDB (4.30%-6.46%). We assembled information from the
      various databases for individual TFs, including annotations and details of their
      developmental stage- and tissue-specific expression patterns. Based on this
      information, we identified 1257 developmental stage-specific TFs and 1104 tissue
      specific TFs, accounting for 52.22% and 45.87% of the 2407 wheat TFs,
      respectively. We identified 338, 269, 262, 175, 49, and 18 tissue-specific TFs in
      the flower, seed, root, leaf, stem, and crown, respectively. There were 100, 6,
      342, 141, 390, and 278 TFs specifically expressed at the dormant seed,
      germinating seed, reproductive, ripening, seedling, and vegetative stages,
      respectively. We constructed a comprehensive database of wheat TFs, designated as
      WheatTFDB ( http://xms.sicau.edu.cn/wheatTFDB/ ). CONCLUSIONS: Approximately
      2.22% (2407 genes) of all genes in the wheat genome were identified as TFs, and
      were clustered into 63 TF families. We identified 1257 developmental stage
      specific TFs and 1104 tissue-specific TFs, based on information about their
      developmental- and tissue-specific expression patterns obtained from publicly
      available gene expression databases. The 2407 wheat TFs and their annotations are
      summarized in our database, WheatTFDB. These data will be useful identifying
      target TFs involved in the stress response at a particular stage of development.

PMID- 25766309
TI  - The Influence of Phonomotor Treatment on Word Retrieval Abilities in 26
      Individuals With Chronic Aphasia: An Open Trial.
AB  - PURPOSE: The ultimate goal of aphasia therapy should be to achieve gains in
      function that generalize to untrained exemplars and daily conversation. Anomia is
      one of the most disabling features of aphasia. The predominantly lexical/semantic
      approaches used to treat anomia have low potential for generalization due to the
      orthogonality of semantic and phonologic representations; this has been borne out
      in a meta-analysis of treatment studies. The intensive, neurally distributed,
      phonologic therapy reported here can, in principle, generalize to untrained
      phonologic sequences because of extant regularities in phonologic sequence
      knowledge and should, in principle, generalize to production of words trained as
      well as those untrained. METHOD: Twenty-six persons with chronic aphasia due to
      stroke were treated, in a staggered (immediate vs. delayed treatment) open trial
      design, with 60 hr of intensive, multimodal therapy designed to enhance access to
      and efficiency of phonemes and phonologic sequences. RESULTS: There was an
      absolute increase of 5% in confrontation naming of "untrained" nouns at 3 months,
      and there were 9% to 10% increases on measures of generalization of phonologic
      processes. CONCLUSION: The results of this trial demonstrate generalization of
      training effects on laboratory measures, which were sustained at 3 months, and
      provide support for the theories that motivated the treatment.

PMID- 25766310
TI  - One-year mortality rates in US children with end-stage renal disease.
AB  - BACKGROUND/AIMS: Few published data describe survival rates for pediatric end
      stage renal disease (ESRD) patients. We aimed to describe one-year mortality
      rates for US pediatric ESRD patients over a 15-year period. METHODS: In this
      retrospective cohort study, we used the US Renal Data System database to identify
      period-prevalent cohorts of patients aged younger than 19 for each year during
      the period 1995-2010. Yearly cohorts averaged approximately 1,200 maintenance
      dialysis patients (60% hemodialysis, 40% peritoneal dialysis) and 1,100
      transplant recipients. Patients were followed for up to 1 year and censored at
      change in modality, loss to follow-up, or death. We calculated the unadjusted
      model-based mortality rates per time at risk, within each cohort year, by
      treatment modality (hemodialysis, peritoneal dialysis, transplant) and patient
      characteristics; percentage of deaths by cause; and overall adjusted odds of
      mortality by characteristics and modality. RESULTS: Approximately 50% of patients
      were in the age group 15-18, 55% were male, and 45% were female. The most common
      causes of ESRD were congenital/reflux/obstructive causes (55%) and
      glomerulonephritis (30%). One-year mortality rates showed evidence of a decrease
      in the number of peritoneal dialysis patients (6.03 per 100 patient-years, 1995;
      2.43, 2010; p = 0.0263). Mortality rates for transplant recipients (average 0.68
      per 100 patient-years) were consistently lower than the rates for all dialysis
      patients (average 4.36 per 100 patient-years). CONCLUSIONS: One-year mortality
      rates differ by treatment modality in pediatric ESRD patients.

PMID- 25766312
TI  - Histone deacetylation meets miRNA: epigenetics and post-transcriptional
      regulation in cancer and chronic diseases.
AB  - INTRODUCTION: Epigenetic regulation via DNA methylation, histone acetylation, as
      well as by microRNAs (miRNAs) is currently in the scientific focus due to its
      role in carcinogenesis and its involvement in initiation, progression and
      metastasis. While many target genes of DNA methylation, histone acetylation and
      miRNAs are known, even less information exists as to how these mechanisms
      cooperate and how they may regulate each other in a specific pathological
      context. For further development of therapeutic approaches, this review presents
      the current status of the crosstalk of histone acetylation and miRNAs in human
      carcinogenesis and chronic diseases. AREAS COVERED: This article reviews
      information from comprehensive PubMed searches to evaluate relevant literature
      with a focus on possible association between histone acetylation, miRNAs and
      their targets. Our analysis identified specific miRNAs which collaborate with
      histone deacetylases (HDACs) and cooperatively regulate several relevant target
      genes. EXPERT OPINION: Fourteen miRNAs could be linked to the expression of eight
      HDACs influencing the alpha-(1,6)-fucosyltransferase, polycystin-2 and the
      fibroblast-growth-factor 2 pathways. Focusing on the complex linkage of miRNA and
      HDAC expression could give deeper insights in new 'druggable' targets and might
      provide possible novel therapeutic approaches in future.

PMID- 25766313
TI  - In vitro evaluation of cytomegalovirus-specific hyperimmune globulins vs.
      standard intravenous immunoglobulins.
AB  - BACKGROUND AND OBJECTIVES: To evaluate standard intravenous immunoglobulin (IVIG)
      as an alternative to intravenous cytomegalovirus hyperimmune immunoglobulin
      (CMVIG) for prophylaxis and therapy of cytomegalovirus (CMV) disease, we measured
      the ELISA and neutralizing titres of CMV-specific antibodies in CMVIG and IVIG
      preparations. MATERIALS AND METHODS: Anti-CMV-IgG ELISA and neutralizing titres
      (fibroblast-based test) in CMVIG CG (Cytogam(r), n = 20), CMVIG CT (Cytotect(r)
      CP, n = 3), IVIG P (Privigen(r), n = 32) and IVIG K/G (Kiovig(r)/Gammagard(r), n
      = 5) were compared, and IgG subclasses 1-4 were determined by nephelometry.
      RESULTS: Cytomegalovirus hyperimmune immunoglobulins contained more than fourfold
      higher CMV ELISA and CMV-neutralizing activity per gram of IgG than the standard
      IVIGs. Pooled data for all four products showed a significant correlation between
      anti-CMV-IgG ELISA and neutralizing titres (r = 0.93, P < 0.001). There was a
      good correlation between the IgG3 content and CMV-neutralizing antibodies amongst
      lots of CMVIGs (r = 0.91, P = 0.01), but this did not extend to the IVIGs. CMVIG
      CG contained the highest CMV-neutralizing activity (3497 +/- 395 PEIU/g IgG) of
      any product tested. CONCLUSION: The higher anti-CMV neutralization capacity of
      CMVIG per gram of IgG vs. standard IVIG suggests that standard IVIGs are not
      equivalent to or interchangeable with CMVIG.

PMID- 25766314
TI  - Screening for autism spectrum disorder in very preterm infants during early
      childhood.
AB  - AIM: The aim of the study was to screen very preterm infants for autism spectrum
      disorder (ASD) with comparisons to a group of term controls. The study also aimed
      to identify maternal and neonatal risk factors, development and behaviour
      associated with a positive screen in the preterm group. METHOD: Preterm infants
      born <= 30 weeks gestation and term infants were recruited at two years of age.
      The mothers were posted the questionnaires and completed the Modified Checklist
      for Autism in Toddlers (M-CHAT), the Child Behaviour Checklist (CBCL) and the
      Depression, Anxiety and Stress Scales (DASS). Previously collected data from the
      mothers at 12 months--the Edinburgh Postnatal Depression Scales (EPDS) were
      analysed. The children had neurodevelopmental assessment including the Bayley
      III. Infants positive on M-CHAT screen had an M-CHAT follow-up interview by phone
      and then were assessed by a developmental paediatrician as indicated with a
      diagnosis of autism being made on clinical judgement. RESULTS: 13 (13.4%) of the
      97 preterm infants screened positive on the M-CHAT compared to three (3.9%) of
      the 77 term infants (p = 0.036). On follow-up interview, three of the preterm
      infants remained positive (one was diagnosed with autism) compared to none of the
      term infants. The preterm infants who screened positive were born to younger, non
      Caucasian mothers and were of lower birth weight and had a higher incidence of
      being small for gestational age (SGA). The infants had lower composite scores on
      Bayley-III and had more internalising and externalising behaviours on the CBCL.
      The mothers had more emotional problems on the DASS and higher scores on the
      EPDS. On multivariate analysis, SGA, greater internalising behaviours and higher
      EPDS scores remained statistically significant. CONCLUSIONS: A positive screen on
      the M-CHAT occurs more commonly in very preterm infants than those born at term.
      Internalising behaviours and maternal mental health are associated with a
      positive screen in the preterm cohort.

PMID- 25766315
TI  - Synthesis of difluoromethyl thioethers from difluoromethyl trimethylsilane and
      organothiocyanates generated in situ.
AB  - A copper-CF2 H complex generated in situ from copper thiocyanate and TMS?CF2 H
      smoothly converts organothiocyanates into valuable difluoromethyl thioethers.
      This reaction step can be combined with several thiocyanation methods to one-pot
      protocols, allowing late-stage difluoromethylthiolations of widely available
      alkyl halides and arenediazonium salts. This strategy enables the introduction of
      difluoromethylthio groups-a largely unexplored substituent with highly promising
      properties-into drug-like molecules. 

PMID- 25766316
TI  - MicroRNA-532-3p regulates mitochondrial fission through targeting apoptosis
      repressor with caspase recruitment domain in doxorubicin cardiotoxicity.
AB  - Doxorubicin (DOX) is a wide-spectrum antitumor drug, but its clinical application
      is limited by its cardiotoxicity. However, the mechanisms underlying DOX-induced
      cardiomyopathy remain mostly unclear. Here we observed that apoptosis repressor
      with caspase recruitment domain (ARC) was downregulated in mouse heart and
      cardiomyocytes upon DOX treatment. Furthermore, enforced expression of ARC
      attenuated DOX-induced cardiomyocyte mitochondrial fission and apoptosis. ARC
      transgenic mice demonstrated reduced cardiotoxicity upon DOX administration. DOX
      induced mitochondrial fission required the activity of dynamin-related protein 1
      (Drp1). In elucidating the molecular mechanism by which ARC was downregulated
      upon DOX treatment, miR-532-3p was found to directly target ARC and participated
      in DOX-induced mitochondrial fission and apoptosis. MiR-532-3p was not involved
      in DOX-induced apoptosis in cancer cells. Taken together, these findings provide
      novel evidence that miR-532-3p and ARC constitute an antiapoptotic pathway that
      regulates DOX cardiotoxicity. Therefore, the development of new therapeutic
      strategies based on ARC and miR-532-3p is promising for overcoming the
      cardiotoxicity of chemotherapy for cancer therapy. 

PMID- 25766317
TI  - Reactive oxygen species and p21Waf1/Cip1 are both essential for p53-mediated
      senescence of head and neck cancer cells.
AB  - Treatment of head and neck squamous cell carcinoma, HNSCC, often requires
      multimodal therapy, including radiation therapy. The efficacy of radiotherapy in
      controlling locoregional recurrence, the most frequent cause of death from HNSCC,
      is critically important for patient survival. One potential biomarker to
      determine radioresistance is TP53 whose alterations are predictive of poor
      radiation response. DNA-damaging reactive oxygen species (ROS) are a by-product
      of ionizing radiation that lead to the activation of p53, transcription of
      p21(cip1/waf1) and, in the case of wild-type TP53 HNSCC cells, cause senescence.
      The expression of p21 and production of ROS have been associated with the
      induction of cellular senescence, but the intricate relationship between p21 and
      ROS and how they work together to induce senescence remains elusive. For the
      first time, we show that persistent exposure to low levels of the ROS, hydrogen
      peroxide, leads to the long-term expression of p21 in HNSCC cells with a
      partially functional TP53, resulting in senescence. We conclude that the level of
      ROS is crucial in initiating p53's transcription of p21 leading to senescence. It
      is p21's ability to sustain elevated levels of ROS, in turn, that allows for a
      long-term oxidative stress, and ensures an active p53-p21-ROS signaling loop. Our
      data offer a rationale to consider the use of either ROS inducing agents or
      therapies that increase p21 expression in combination with radiation as
      approaches in cancer therapy and emphasizes the importance of considering TP53
      status when selecting a patient's treatment options. 

PMID- 25766318
TI  - A transgenic mouse model to inducibly target prosurvival Bcl2 proteins with
      selective BH3 peptides in vivo.

PMID- 25766319
TI  - Variola virus F1L is a Bcl-2-like protein that unlike its vaccinia virus
      counterpart inhibits apoptosis independent of Bim.
AB  - Subversion of host cell apoptosis is an important survival strategy for viruses
      to ensure their own proliferation and survival. Certain viruses express proteins
      homologous in sequence, structure and function to mammalian pro-survival B-cell
      lymphoma 2 (Bcl-2) proteins, which prevent rapid clearance of infected host
      cells. In vaccinia virus (VV), the virulence factor F1L was shown to be a potent
      inhibitor of apoptosis that functions primarily be engaging pro-apoptotic Bim.
      Variola virus (VAR), the causative agent of smallpox, harbors a homolog of F1L of
      unknown function. We show that VAR F1L is a potent inhibitor of apoptosis, and
      unlike all other characterized anti-apoptotic Bcl-2 family members lacks affinity
      for the Bim Bcl-2 homology 3 (BH3) domain. Instead, VAR F1L engages Bid BH3 as
      well as Bak and Bax BH3 domains. Unlike its VV homolog, variola F1L only protects
      against Bax-mediated apoptosis in cellular assays. Crystal structures of variola
      F1L bound to Bid and Bak BH3 domains reveal that variola F1L forms a domain
      swapped Bcl-2 fold, which accommodates Bid and Bak BH3 in the canonical Bcl-2
      binding groove, in a manner similar to VV F1L. Despite the observed conservation
      of structure and sequence, variola F1L inhibits apoptosis using a startlingly
      different mechanism compared with its VV counterpart. Our results suggest that
      unlike during VV infection, Bim neutralization may not be required during VAR
      infection. As molecular determinants for the human-specific tropism of VAR remain
      essentially unknown, identification of a different mechanism of action and
      utilization of host factors used by a VAR virulence factor compared with its VV
      homolog suggest that studying VAR directly may be essential to understand its
      unique tropism. 

PMID- 25766321
TI  - PAK1 regulates RUFY3-mediated gastric cancer cell migration and invasion.
AB  - Actin protrusion at the cell periphery is central to the formation of invadopodia
      during tumor cell migration and invasion. Although RUFY3 (RUN and FYVE domain
      containing 3)/SINGAR1 (single axon-related1)/RIPX (Rap2 interacting protein X)
      has an important role in neuronal development, its pathophysiologic role and
      relevance to cancer are still largely unknown. The purpose of this study was to
      elucidate the molecular mechanisms by which RUFY3 involves in gastric cancer cell
      migration and invasion. Here, our data show that overexpression of RUFY3 leads to
      the formation of F-actin-enriched protrusive structures at the cell periphery and
      induces gastric cancer cell migration. Furthermore, P21-activated kinase-1 (PAK1)
      interacts with RUFY3, and promotes RUFY3 expression and RUFY3-induced gastric
      cancer cell migration; inhibition of PAK1 attenuates RUFY3-induced SGC-7901 cell
      migration and invasion. Importantly, we found that the inhibitory effect of cell
      migration and invasion is significantly enhanced by knockdown of both PAK1 and
      RUFY3 compared with knockdown of RUFY3 alone or PAK1 alone. Strikingly, we found
      significant upregulation of RUFY3 in gastric cancer samples with invasive
      carcinoma at pathologic TNM III and TNM IV stages, compared with their non-tumor
      counterparts. Moreover, an obvious positive correlation was observed between the
      protein expression of RUFY3 and PAK1 in 40 pairs of gastric cancer samples.
      Therefore, these findings provide important evidence that PAK1 can positively
      regulate RUFY3 expression, which contribute to the metastatic potential of
      gastric cancer cells, maybe blocking PAK1-RUFY3 signaling would become a
      potential metastasis therapeutic strategy for gastric cancer. 

PMID- 25766320
TI  - KLF17 empowers TGF-beta/Smad signaling by targeting Smad3-dependent pathway to
      suppress tumor growth and metastasis during cancer progression.
AB  - Inhibition of tumor suppressive signaling is linked to cancer progression,
      metastasis and epithelial-mesenchymal transition (EMT). Transforming growth
      factor-beta1 (TGF-beta)/Smad signaling plays an important role in tumor
      suppression. Kruppel-like-factor 17 (KLF17) is a negative regulator of metastasis
      and EMT. However, underlying mechanisms leading to tumor suppressive and anti
      metastatic function of KLF17 still remains unknown. Here, we show that KLF17
      plays an integral role in potentiating TGF-beta/Smad signaling via Smad3
      dependent pathway to suppress tumor progression. Intriguingly, TGF-beta/Smad3
      signaling induces KLF17 expression, generating a positive feedback loop. TGF
      beta/Smad3-KLF17 loop is critical for anti-metastasis and tumor inhibition in
      cancer cells. Mechanistically, silencing KLF17 reduced Smad3-DNA complex
      formation on Smad binding element (SBE) and affects the expression of TGF
      beta/Smad target genes. Moreover, KLF17 alters Smad3 binding pattern on
      chromatin. KLF17 regulates TGF-beta target genes that are Smad3-dependent. Smad3
      and KLF17 physically interact with each other via KLF17 responsive elements/SBE
      region. Intriguingly, TGF-beta stimulates the recruitment of KLF17 on chromatin
      to subsets of metastasis-associated genes. Functionally, depletion of KLF17
      enhanced tumorigenic features in cancer cells. KLF17 is critical for full
      cytostatic function of TGF-beta/Smad signaling. Clinically, KLF17 expression
      significantly decreases during advance HCC. KLF17 shows positive correlation with
      Smad3 levels in cancer samples. Our data shows that enhance KLF17 activity has
      important therapeutic implications for targeted-therapies aimed at TGF-beta/Smad3
      pathway. These findings define novel mechanism by which TGF-beta/Smad-KLF17
      pathway mutually affect each other during cancer metastasis, provide a new model
      of regulation of TGF-beta/Smad signaling by KLF17 and defines new insights into
      anti-metastatic function of KLF17. 

PMID- 25766322
TI  - Plasma membrane poration by opioid neuropeptides: a possible mechanism of
      pathological signal transduction.
AB  - Neuropeptides induce signal transduction across the plasma membrane by acting
      through cell-surface receptors. The dynorphins, endogenous ligands for opioid
      receptors, are an exception; they also produce non-receptor-mediated effects
      causing pain and neurodegeneration. To understand non-receptor mechanism(s), we
      examined interactions of dynorphins with plasma membrane. Using fluorescence
      correlation spectroscopy and patch-clamp electrophysiology, we demonstrate that
      dynorphins accumulate in the membrane and induce a continuum of transient
      increases in ionic conductance. This phenomenon is consistent with stochastic
      formation of giant (~2.7 nm estimated diameter) unstructured non-ion-selective
      membrane pores. The potency of dynorphins to porate the plasma membrane
      correlates with their pathogenic effects in cellular and animal models. Membrane
      poration by dynorphins may represent a mechanism of pathological signal
      transduction. Persistent neuronal excitation by this mechanism may lead to
      profound neuropathological alterations, including neurodegeneration and cell
      death. 

PMID- 25766323
TI  - BAG3 regulates formation of the SNARE complex and insulin secretion.
AB  - Insulin release in response to glucose stimulation requires exocytosis of insulin
      containing granules. Glucose stimulation of beta cells leads to focal adhesion
      kinase (FAK) phosphorylation, which acts on the Rho family proteins (Rho, Rac and
      Cdc42) that direct F-actin remodeling. This process requires docking and fusion
      of secretory vesicles to the release sites at the plasma membrane and is a
      complex mechanism that is mediated by SNAREs. This transiently disrupts the F
      actin barrier and allows the redistribution of the insulin-containing granules to
      more peripheral regions of the beta cell, hence facilitating insulin secretion.
      In this manuscript, we show for the first time that BAG3 plays an important role
      in this process. We show that BAG3 downregulation results in increased insulin
      secretion in response to glucose stimulation and in disruption of the F-actin
      network. Moreover, we show that BAG3 binds to SNAP-25 and syntaxin-1, two
      components of the t-SNARE complex preventing the interaction between SNAP-25 and
      syntaxin-1. Upon glucose stimulation BAG3 is phosphorylated by FAK and
      dissociates from SNAP-25 allowing the formation of the SNARE complex,
      destabilization of the F-actin network and insulin release. 

PMID- 25766325
TI  - A benzimidazole derivative exhibiting antitumor activity blocks EGFR and HER2
      activity and upregulates DR5 in breast cancer cells.
AB  - Aberrant expression or function of epidermal growth factor receptor (EGFR) or the
      closely related human epidermal growth factor receptor 2 (HER2) can promote cell
      proliferation and survival, thereby contributing to tumorigenesis. Specific
      antibodies and low-molecular-weight tyrosine kinase inhibitors of both proteins
      are currently in clinical trials for cancer treatment. Benzimidazole derivatives
      possess diverse biological activities, including antitumor activity. However, the
      anticancer mechanism of 5a (a 2-aryl benzimidazole compound; 2-chloro-N-(2-p
      tolyl-1H-benzo[d]imidazol-5-yl)acetamide, C(16)H(14)ClN(3)O, MW299), a novel 2
      aryl benzimidazole derivative, toward breast cancer is largely unknown. Here, we
      demonstrate that 5a potently inhibited both EGFR and HER2 activity by reducing
      EGFR and HER2 tyrosine phosphorylation and preventing downstream activation of
      PI3K/Akt and MEK/Erk pathways in vitro and in vivo. We also show that 5a
      inhibited the phosphorylation of FOXO and promoted FOXO translocation from the
      cytoplasm into the nucleus, resulting in the G1-phase cell cycle arrest and
      apoptosis. Moreover, 5a potently induced apoptosis via the c-Jun N-terminal
      kinase (JNK)-mediated death receptor 5 upregulation in breast cancer cells. The
      antitumor activity of 5a was consistent with additional results demonstrating
      that 5a significantly reduced tumor volume in nude mice in vivo. Analysis of the
      primary breast cancer cell lines with HER2 overexpression further confirmed that
      5a significantly inhibited Akt Ser473 and Bad Ser136 phosphorylation and reduced
      cyclin D3 expression. On the basis of our findings, further development of this 2
      aryl benzimidazole derivative, a new class of multitarget anticancer agents, is
      warranted and represents a novel strategy for improving breast cancer treatment.

PMID- 25766324
TI  - Readthrough acetylcholinesterase (AChE-R) and regulated necrosis: pharmacological
      targets for the regulation of ovarian functions?
AB  - Proliferation, differentiation and death of ovarian cells ensure orderly
      functioning of the female gonad during the reproductive phase, which ultimately
      ends with menopause in women. These processes are regulated by several
      mechanisms, including local signaling via neurotransmitters. Previous studies
      showed that ovarian non-neuronal endocrine cells produce acetylcholine (ACh),
      which likely acts as a trophic factor within the ovarian follicle and the corpus
      luteum via muscarinic ACh receptors. How its actions are restricted was unknown.
      We identified enzymatically active acetylcholinesterase (AChE) in human ovarian
      follicular fluid as a product of human granulosa cells. AChE breaks down ACh and
      thereby attenuates its trophic functions. Blockage of AChE by huperzine A
      increased the trophic actions as seen in granulosa cells studies. Among ovarian
      AChE variants, the readthrough isoform AChE-R was identified, which has further,
      non-enzymatic roles. AChE-R was found in follicular fluid, granulosa and theca
      cells, as well as luteal cells, implying that such functions occur in vivo. A
      synthetic AChE-R peptide (ARP) was used to explore such actions and induced in
      primary, cultured human granulosa cells a caspase-independent form of cell death
      with a distinct balloon-like morphology and the release of lactate dehydrogenase.
      The RIPK1 inhibitor necrostatin-1 and the MLKL-blocker necrosulfonamide
      significantly reduced this form of cell death. Thus a novel non-enzymatic
      function of AChE-R is to stimulate RIPK1/MLKL-dependent regulated necrosis
      (necroptosis). The latter complements a cholinergic system in the ovary, which
      determines life and death of ovarian cells. Necroptosis likely occurs in the
      primate ovary, as granulosa and luteal cells were immunopositive for phospho
      MLKL, and hence necroptosis may contribute to follicular atresia and luteolysis.
      The results suggest that interference with the enzymatic activities of AChE
      and/or interference with necroptosis may be novel approaches to influence ovarian
      functions. 

PMID- 25766326
TI  - Endometrial cancer-associated mutants of SPOP are defective in regulating
      estrogen receptor-alpha protein turnover.
AB  - Increasing amounts of evidence strongly suggests that dysregulation of ubiquitin
      proteasome system is closely associated with cancer pathogenesis. Speckle-type
      POZ protein (SPOP) is an adapter protein of the CUL3-based E3 ubiquitin ligase
      complexes. It selectively recruits substrates for their ubiquitination and
      subsequent degradation. Recently, several exome-sequencing studies of endometrial
      cancer revealed high frequency somatic mutations in SPOP (5.7-10%). However, how
      SPOP mutations contribute to endometrial cancer remains unknown. Here, we
      identified estrogen receptor-alpha (ERalpha), a major endometrial cancer
      promoter, as a substrate for the SPOP-CUL3-RBX1 E3 ubiquitin ligase complex. SPOP
      specifically recognizes multiple Ser/Thr (S/T)-rich degrons located in the AF2
      domain of ERalpha, and triggers ERalpha degradation via the ubiquitin-proteasome
      pathway. SPOP depletion by siRNAs promotes endometrial cells growth. Strikingly,
      endometrial cancer-associated mutants of SPOP are defective in regulating ERalpha
      degradation and ubiquitination. Furthermore, we found that SPOP participates in
      estrogen-induced ERalpha degradation and transactivation. Our study revealed
      novel molecular mechanisms underlying the regulation of ERalpha protein
      homeostasis in physiological and pathological conditions, and provided insights
      in understanding the relationship between SPOP mutations and the development of
      endometrial cancer. 

PMID- 25766327
TI  - Fgf9 inhibition of meiotic differentiation in spermatogonia is mediated by Erk
      dependent activation of Nodal-Smad2/3 signaling and is antagonized by Kit Ligand.
AB  - Both fibroblast growth factor 9 (Fgf9) and Kit Ligand (Kl) signal through
      tyrosine kinase receptors, yet they exert opposite effects on meiotic
      differentiation in postnatal spermatogonia, Fgf9 acting as a meiosis-inhibiting
      substance and Kl acting as a promoter of the differentiation process. To
      understand the molecular mechanisms that might underlie this difference, we tried
      to dissect the intracellular signaling elicited by these two growth factors. We
      found that both Fgf9 and Kl stimulate Erk1/2 activation in Kit+ (differentiating)
      spermatogonia, even though with different time courses, whereas Kl, but not Fgf9,
      elicits activation of the Pi3k-Akt pathway. Sustained Erk1/2 activity promoted by
      Fgf9 is required for induction of the autocrine Cripto-Nodal-Smad2/3 signaling
      loop in these cells. Nodal signaling, in turn, is essential to mediate Fgf9
      suppression of the meiotic program, including inhibition of Stra8 and Scp3
      expression and induction of the meiotic gatekeeper Nanos2. On the contrary,
      sustained activation of the Pi3k-Akt pathway is required for the induction of
      Stra8 expression elicited by Kl and retinoic acid. Moreover, we found that Kl
      treatment impairs Nodal mRNA expression and Fgf9-mediated Nanos2 induction,
      reinforcing the antagonistic effect of these two growth factors on the meiotic
      fate of male germ cells. 

PMID- 25766328
TI  - Prognostic significance of Cbx4 expression and its beneficial effect for
      transarterial chemoembolization in hepatocellular carcinoma.
AB  - Our recent investigations showed that polycomb chromobox 4 (Cbx4) promotes
      angiogenesis and metastasis of hepatocellular carcinoma (HCC) through its
      sumoylating action on hypoxia-inducible factor-1alpha protein. Here, we attempt
      to identify the prognostic significances of Cbx4 by a retrospective analyses in
      727 cases of HCC patients with and without postoperative transarterial
      chemoembolization (TACE) or transarterial embolization (TAE). Binary logistic
      regression tests indicated that Cbx4 is correlated with histological grading,
      tumor-node-metastasis stage, microvessel density, distant metastasis and
      hematogenous metastasis of HCC. By univariate and multivariate analyses, we show
      that Cbx4 is an independent prognostic factor of HCC, and both TAE and TACE
      treatments have no effects on the overall survival in HCC patients with low Cbx4
      expression. More intriguingly, TACE prolongs, while TAE shortens, the overall
      survival of HCC patients with high Cbx4 expression, indicating that Cbx4 is a
      good biomarker on decision-making to perform postoperative TACE in HCC patients.
      Moreover, Cbx4 overexpression enhances while Cbx4 silencing antagonizes
      doxorubicin-induced cell death of HCC cell lines. In conclusion, Cbx4 is an
      independent prognostic factor for HCC patients, and the patients with high Cbx4
      expression should receive postoperative TACE treatment to improve their survival.

PMID- 25766329
TI  - Life or death by NFkappaB, Losartan promotes survival in dy2J/dy2J mouse of
      MDC1A.
AB  - Inflammation and fibrosis are well-defined mechanisms involved in the
      pathogenesis of the incurable Laminin alpha2-deficient congenital muscular
      dystrophy (MDC1A), while apoptosis mechanism is barely discussed. Our previous
      study showed treatment with Losartan, an angiotensin II type I receptor
      antagonist, improved muscle strength and reduced fibrosis through transforming
      growth factor beta (TGF-beta) and mitogen-activated protein kinases (MAPK)
      signaling inhibition in the dy(2J)/dy(2J) mouse model of MDC1A. Here we show for
      the first time that Losartan treatment up-regulates and shifts the nuclear factor
      kappa B (NFkappaB) signaling pathway to favor survival versus apoptosis/damage in
      this animal model. Losartan treatment was associated with significantly increased
      serum tumor necrosis factor alpha (TNF-alpha) level, p65 nuclei accumulation, and
      decreased muscle IkappaB-beta protein level, indicating NFkappaB activation.
      Moreover, NFkappaB anti-apoptotic target genes TNF receptor-associated factor 1
      (TRAF1), TNF receptor-associated factor 2 (TRAF2), cellular inhibitor of
      apoptosis (cIAP2), and Ferritin heavy chain (FTH1) were increased following
      Losartan treatment. Losartan induced protein expression toward a pro-survival
      profile as BCL-2 expression levels were increased and Caspase-3 expression levels
      were decreased. Muscle apoptosis reduction was further confirmed using terminal
      deoxynucleotidyltransferase-mediated dUTP nick end labeling (TUNEL) assay. Thus,
      along with TGF-beta and MAPK signaling, NFkappaB serves as an important
      regulatory pathway which following Losartan treatment promotes survival in the
      dy(2J)/dy(2J) mouse model of MDC1A. 

PMID- 25766332
TI  - Ultrafast Electron Transfer Dynamics in a Series of Porphyrin/Viologen Complexes:
      Involvement of Electronically Excited Radical Pair Products.
AB  - Ultrafast electron transfer was studied for a series of
      metalloporphyrin/bipyridinium complexes in aqueous solution, using laser
      excitation in the Soret or Q-bands of the porphyrin. Electron transfer occurred
      before electronic and vibrational relaxation of the initial excited state. This
      allowed for a thorough investigation of the dependence of electron transfer rate
      constants on the driving force and the nature of the product state. The driving
      force dependence showed that electron transfer from the S2 state occurred to an
      electronically excited radical pair state, and the present results provide the
      most direct evidence to date for the formation of such states in photoinduced
      electron transfer reactions. We also found that subsequent recombination of the
      radical pair produced vibrationally excited ground states; the excess energy of
      the radical pair generated from the initial state is not completely dissipated
      during the lifetime of the radical pair. The porphyrin/bipyridinium complexes
      where recombination lies deeper in the Marcus inverted region show less formation
      of unrelaxed ground states, contrary to what is expected from equilibrium
      electron transfer theories. Instead, the rate of the electron transfer, which
      competes with vibrational relaxation, was the main parameter controlling the
      relative yield of unrelaxed ground states within this series of complexes. 

PMID- 25766331
TI  - NIK is required for NF-kappaB-mediated induction of BAG3 upon inhibition of
      constitutive protein degradation pathways.
AB  - Recently, we reported that induction of the co-chaperone Bcl-2-associated
      athanogene 3 (BAG3) is critical for recovery of rhabdomyosarcoma (RMS) cells
      after proteotoxic stress upon inhibition of the two constitutive protein
      degradation pathways, that is, the ubiquitin-proteasome system by Bortezomib and
      the aggresome-autophagy system by histone deacetylase 6 (HDAC6) inhibitor ST80.
      In the present study, we investigated the molecular mechanisms mediating BAG3
      induction under these conditions. Here, we identify nuclear factor-kappa B (NF
      kappaB)-inducing kinase (NIK) as a key mediator of ST80/Bortezomib-stimulated NF
      kappaB activation and transcriptional upregulation of BAG3. ST80/Bortezomib
      cotreatment upregulates mRNA and protein expression of NIK, which is accompanied
      by an initial increase in histone H3 acetylation. Importantly, NIK silencing by
      siRNA abolishes NF-kappaB activation and BAG3 induction by ST80/Bortezomib.
      Furthermore, ST80/Bortezomib cotreatment stimulates NF-kappaB transcriptional
      activity and upregulates NF-kappaB target genes. Genetic inhibition of NF-kappaB
      by overexpression of dominant-negative IkappaBalpha superrepressor (IkappaBalpha
      SR) or by knockdown of p65 blocks the ST80/Bortezomib-stimulated upregulation of
      BAG3 mRNA and protein expression. Interestingly, inhibition of lysosomal activity
      by Bafilomycin A1 inhibits ST80/Bortezomib-stimulated IkappaBalpha degradation,
      NF-kappaB activation and BAG3 upregulation, indicating that IkappaBalpha is
      degraded via the lysosome in the presence of Bortezomib. Thus, by demonstrating a
      critical role of NIK in mediating NF-kappaB activation and BAG3 induction upon
      ST80/Bortezomib cotreatment, our study provides novel insights into mechanisms of
      resistance to proteotoxic stress in RMS. 

PMID- 25766330
TI  - Cytochrome c oxidase deficiency accelerates mitochondrial apoptosis by activating
      ceramide synthase 6.
AB  - Although numerous pathogenic changes within the mitochondrial respiratory chain
      (RC) have been associated with an elevated occurrence of apoptosis within the
      affected tissues, the mechanistic insight into how mitochondrial dysfunction
      initiates apoptotic cell death is still unknown. In this study, we show that the
      specific alteration of the cytochrome c oxidase (COX), representing a common
      defect found in mitochondrial diseases, facilitates mitochondrial apoptosis in
      response to oxidative stress. Our data identified an increased ceramide synthase
      6 (CerS6) activity as an important pro-apoptotic response to COX dysfunction
      induced either by chemical or genetic approaches. The elevated CerS6 activity
      resulted in accumulation of the pro-apoptotic C16 : 0 ceramide, which facilitates
      the mitochondrial apoptosis in response to oxidative stress. Accordingly,
      inhibition of CerS6 or its specific knockdown diminished the increased
      susceptibility of COX-deficient cells to oxidative stress. Our results provide
      new insights into how mitochondrial RC dysfunction mechanistically interferes
      with the apoptotic machinery. On the basis of its pivotal role in regulating cell
      death upon COX dysfunction, CerS6 might potentially represent a novel target for
      therapeutic intervention in mitochondrial diseases caused by COX dysfunction. 

PMID- 25766333
TI  - Computed tomography and magnetic resonance imaging findings of ureteral myxedema
      in Graves' disease.
AB  - Ureteral myxedema is exceptionally rare. We describe computed tomography and
      magnetic resonance imaging findings in a case of ureteral myxedema. The
      demonstration of water-like hyperintensity around the ureteral lumen on heavily
      T2-weighted sequences should be considered a strongly suggestive sign for
      ureteral myxedema. 

PMID- 25766334
TI  - Elevated serum free pregnancy-associated plasma protein-A independently predicts
      mortality in haemodialysis patients but is not associated with recurrent
      haemodialysis-induced ischaemic myocardial injury.
AB  - BACKGROUND/AIMS: Pregnancy-associated plasma protein-A (PAPP-A) is a putative
      marker of atheroma instability and ischaemic myocardial stress prior to necrosis.
      Total PAPP-A (tPAPP-A) levels in acute coronary syndromes predict adverse
      outcomes. However, free PAPP-A (fPAPP-A) predominates in the circulation.
      Ischaemic haemodialysis (HD)-induced cardiac injury (myocardial stunning) is
      common and is associated with markers of myocardial necrosis, inflammation,
      cardiovascular events and mortality. Coronary plaque instability in
      pathophysiology of HD-induced myocardial stunning has not been studied. We aimed
      to investigate the relationship of fPAPP-A with stunning and mortality. METHODS:
      130 prevalent patients from two HD centres (Finland and UK) were studied. Pre-HD
      free, complexed and total PAPP-A were measured by immunoassay. A subset of 62
      patients underwent echocardiography to assess HD-induced myocardial stunning. The
      mean duration of follow-up was 407 +/- 98 days. RESULTS: fPAPP-A was elevated
      (median: 3.45 mIU/l) and correlated with dialysis vintage (r = 0.391, p < 0.001),
      cardiac troponin T (cTnT; r = 0.29, p = 0.001) and cardiac troponin I (cTnI; r =
      0.22, p = 0.01). PAPP-A was not related to stunning. Dialysis vintage and cTnT
      independently predicted Ln fPAPP-A (model R = 0.463). fPAPP-A, cTnT and age
      independently predicted death (Nagelkerke R(2) = 0.362). CONCLUSIONS: fPAPP-A, a
      novel predictor of HD-related mortality, demonstrates better prognostic power
      than tPAPP-A. Coronary plaque instability may contribute to sub-lethal myocardial
      injury, but may not be critical in pathogenesis of HD-induced ischaemic cardiac
      injury.

PMID- 25766335
TI  - Improving peri-operative patient care: the surgical safety checklist.

PMID- 25766336
TI  - Managing advanced stage Hodgkin lymphoma.

PMID- 25766337
TI  - Refining a socio-economic status scale for use in community-based health research
      in India.
AB  - OBJECTIVE: Socio economic status is an important determinant of health and
      disease in population. Various scales for measuring the same exist in modern
      Indian society each with it's own limitations. Present study was done to abridge
      the existing and latest available Aggarwal Scale. STUDY DESIGN: Cross Sectional
      Study. MATERIAL AND METHODS: All relevant information pertaining to Aggarwal et
      al scale was collected for 197 households and analyzed in SPSS 16. Data reduction
      was done using Factor Analysis (FA) under which Principal Components Analysis
      (PCA) was used. RESULTS: Four components were selected based on criteria Eigen
      value of more than one and elbowing in scree plot. All the 22 items of Aggarwal
      et al were divided among these 4 components. Based on factor loadings four
      reduced scales were constructed. Percentage agreement of reduced scales with
      original scale increased as we increased the number of items in the scale.
      Analysis narrowed down the 22 items of Aggarwal et al scale to six items e.g.
      locality, education of husband/ wife, occupation of husband/ wife, family
      possessions, caste and monthly per capita income. These 6 items together
      accounted for 49% of the variation and can be taken as a surrogate measure of SES
      of the family. CONCLUSION: We have presented reduced versions of Aggarwal et al
      scale along with degree of agreement with the original scale. Authors propose the
      use of these scales to measure SES to overcome the time constraint in practicing
      research.

PMID- 25766338
TI  - An audit of histopathology reports of carcinoma endometrium: experience from a
      tertiary referral center.
AB  - BACKGROUND: The aim was to assess compliance to reporting minimum data sets in
      carcinoma endometrium reports, in a team of 13 pathologists, and also to analyze
      parameters such as. tumor size, type, grade, depth of myometrial invasion, lymph
      node yield, pTNM stage etc. MATERIALS AND METHODS: Reports of 114 cases of
      carcinoma endometrium, that were operated in-house during the years 2008 to 2010
      were analyzed from the files of the Pathology department of our hospital.
      RESULTS: The median age was 58.04 years and median tumor size was 4 cm.
      Endometrioid adenocarcinoma was the most common type (82.5%), followed by
      malignant mixed Mullerian tumor (MMMT) (6.1%) and Serous carcinoma (3.5%). Grade
      2 was the commonest tumor grade (42.1%). Less than half of myometrial invasion
      was seen in 50% of the cases and more than half of the myometrial invasion was
      seen in 46.5% of cases. (Information was not available in four cases).
      Parametrial involvement was seen in 5.3% cases. The pTNM stage was not mentioned
      in 71.9% reports. The median lymph node yield was 15. CONCLUSION: The compliance
      to adhere to and to provide minimum data information in carcinoma endometrium
      reports is generally good. Lymph node yield is reasonable. Mentioning of pTNM
      staging is to be done more meticulously. Use of proformas/checklists is
      recommended.

PMID- 25766339
TI  - Treatment results in advanced stage Hodgkin's lymphoma: a retrospective study.
AB  - BACKGROUND: Hodgkin's lymphoma displays distinct epidemiological attributes in
      Asian population thus making it relevant to study whether there are any
      differences in treatment outcomes too when treated with current standard of care.
      AIM: To evaluate the treatment outcomes of de-novo advanced stage HL in adults.
      MATERIALS AND METHODS: This retrospective study included de-novo advanced stage
      HL patients (>=15 years) registered at our center from January 2004 to December
      2007. Treatment outcomes were measured in terms of response rates, overall
      survival (OS) and progression-free survival (PFS). Overall and PFS were
      calculated with Kaplan-Meier methodology and Cox-proportional hazards model was
      used for multivariate analysis to identify prognostic factors. RESULTS: There
      were 125 patients (males 77%) who received minimum one cycle of chemotherapy with
      median age of 32 years (Range 15-65 years). Stage IV disease was seen in (46
      patients) 37%; 75% (94 patients) patients had B symptoms. International
      prognostic score (IPS) <=4 was seen in 95/112 (85%) patients. ABVD (adriamycin,
      bleomycin, vinblastine, dacarbazine) chemotherapy was given to 94%. Radiation to
      residual/bulky sites was given to 36% (45 patients). Response data was available
      for 112 patients; complete response in 76%; partial response in 10 % and
      progressive disease in 3 patients. Nineteen deaths (progressive disease-7,
      toxicity-8, unrelated cause-4) were observed. At median follow-up of 28 months,
      estimated 5-year OS and PFS were 60% and 58%, respectively. On multivariate
      analysis, IPS and response to treatment were significant factors for both OS and
      PFS. CONCLUSIONS: The treatment outcomes in this study are comparable with the
      published literature with limited follow-up data.

PMID- 25766340
TI  - Surgical checklist application and its impact on patient safety in pediatric
      surgery.
AB  - BACKGROUND: Surgical care is an essential component of health care of children
      worldwide. Incidences of congenital anomalies, trauma, cancers and acquired
      diseases continue to rise and along with that the impact of surgical intervention
      on public health system also increases. It then becomes essential that the
      surgical teams make the procedures safe and error proof. The World Health
      Organization (WHO) has instituted the surgical checklist as a global initiative
      to improve surgical safety. AIMS: To assess the acceptance, application and
      adherence to the WHO Safe Surgery Checklist in Pediatric Surgery Practice at a
      university teaching hospital. MATERIALS AND METHODS: In a prospective study,
      spanning 2 years, the checklist was implemented for all patients who underwent
      operative procedures under general anesthesia. The checklist identified three
      phases of an operation, each corresponding to a specific period in the normal
      flow of work: Before the induction of anesthesia ("sign in"), before the skin
      incision ("time out") and before the patient leaves the operating room ("sign
      out"). In each phase, an anesthesiologist,-"checklist coordinator," confirmed
      that the anesthesia, surgery and nursing teams have completed the listed tasks
      before proceeding with the operation and exit. The checklist was used for 3000
      consecutive patients. RESULTS: No major perioperative errors were noted. In 54
      (1.8%) patients, children had the same names and identical surgical procedure
      posted on the same operation list. The patient identification tag was missing in
      four (0.1%) patients. Mention of the side of procedures was missing in 108 (3.6%)
      cases. In 0.1% (3) of patients there was mix up of the mention of side of
      operation in the case papers and consent forms. In 78 (2.6%) patients, the
      consent form was not signed by parents/guardians or the side of the procedure was
      not quoted. Antibiotic orders were missing in five (0.2%) patients. In 12 (0.4%)
      cases, immobilization of the patients was suboptimal, which led to displacement
      of diathermy grounding pad. In 54 (1.8%) patients, the checklist was not used at
      all. In 76 (2.5%) patients the checklist was found to be incompletely filled.
      CONCLUSIONS: Our study supports the use of the checklist as an essential safety
      tool and reinforcement of the same. The checklist may act as a valuable prompt to
      focus the team, to ensure that even the simple things have been cared for.

PMID- 25766341
TI  - Medical students and interns' knowledge about and attitude towards homosexuality.
AB  - BACKGROUND AND RATIONALE: Medical professionals' attitude towards homosexuals
      affects health care offered to such patients with a different sexual orientation.
      There is absence of literature that explores the attitudes of Indian medical
      students or physicians towards homosexuality. AIM: This study aimed to evaluate
      Indian medical students and interns' knowledge about homosexuality and attitude
      towards homosexuals. MATERIALS AND METHODS: After IEC approval and written
      informed consent, a cross-sectional study was conducted on a purposive sample of
      undergraduate medical students and interns studying in one Indian medical
      college. The response rate was 80.5%. Only completely and validly filled
      responses (N = 244) were analyzed. The participants filled the Sex Education and
      Knowledge about Homosexuality Questionnaire (SEKHQ) and the Attitudes towards
      Homosexuals Questionnaire (AHQ). SEKHQ consisted of 32 statements with response
      chosen from 'true', 'false', or 'don't know'. AHQ consisted of 20 statements
      scorable on a 5-point Likert scale. Multiple linear regression was used to find
      the predictors of knowledge and attitude. RESULTS: Medical students and interns
      had inadequate knowledge about homosexuality, although they endorsed a neutral
      stance insofar as their attitude towards homosexuals is concerned. Females had
      more positive attitudes towards homosexuals. Knowledge emerged as the most
      significant predictor of attitude; those having higher knowledge had more
      positive attitudes. CONCLUSION: Enhancing knowledge of medical students by
      incorporation of homosexuality related health issues in the curriculum could help
      reduce prejudice towards the sexual minority and thus impact their future
      clinical practice.

PMID- 25766343
TI  - A case of probable bemiparin-induced HIT type II managed with low-dose
      fondaparinux.

PMID- 25766342
TI  - Heart failure: novel therapeutic approaches.
AB  - Heart failure (HF) is a complex clinical syndrome that can result from any
      structural or functional cardiac disorders that impairs the ability of the
      ventricle to fill with or eject blood. Despite effective medical interventions,
      mortality and morbidity remain substantial. There have been significant advances
      in the therapy of HF in recent decades, such as the introduction of beta-blockers
      and antagonists of the renin-angiotensin system but still there is a major unmet
      need for better therapies for HF. In the present era, pathophysiology of HF has
      been explored. Various novel pathways, molecular sites have been identified,
      which contribute to the progression of the disease. By targeting these sites,
      newer pharmacological agents have been developed, which can play a promising role
      in the treatment of HF. This article focuses on recent advancements in
      pharmacotherapy of HF, which include agents targeting myocardial contractility,
      cytokines and inflammation, fibrosis and remodeling, myocardial metabolism,
      oxidative stress, and other newly defined pathways. 

PMID- 25766344
TI  - Iatrogenic nocturnal eneuresis - an overlooked side effect of anti histamines?
AB  - Nocturnal enuresis is a common disorder in childhood, but its pathophysiological
      mechanisms have not been fully elucidated. Iatrogenic nocturnal enuresis has been
      described following treatment with several psychotropic medications. Herein, we
      describe a 6-year-old child who experienced nocturnal enuresis during treatment
      with the antihistamine cetirizine. Drug rechallenge was positive. Several
      neurotransmitters are implicated in the pathogenesis of nocturnal enuresis,
      including noradrenaline, serotonin and dopamine. Antihistamine treatment may
      provoke functional imbalance of these pathways resulting in incontinence. 

PMID- 25766345
TI  - Hemophagocytic lymphohistiocytosis secondary to infections: a tropical
      experience!
AB  - Hemophagocytic lymphohistiocytosis (HLH) is a potentially fatal hyper
      inflammatory condition, if not recognized and treated in time. A high index of
      suspicion can help identify the condition early. This condition can occur in the
      primary or secondary form. Secondary HLH or hemophagocytic syndrome (HPS)
      secondary to infections is an important clinical entity especially in tropical
      world. In this article, we share our experience with this entity and make an
      attempt to explore literature about ravenous macrophages which occurs secondary
      to infections. It is a series of six cases of HLH secondary to infectious disease
      in our center in a coastal city in South India over last one year with follow up.

PMID- 25766346
TI  - Painful legs and moving toes syndrome responsive to pregabalin.
AB  - Report three cases of painful legs and moving toes (PLMT) syndrome responsive to
      pregabalin along with a review of its literature. Three patients with PLMT
      syndrome improved with pregabalin. The first and third patient reported
      improvement in pain scores, quality of life, and quality of sleep sustained over
      time. The second and third patient had near complete remission of toe movements,
      but pregabalin was discontinued in the second patient due to aggravation of leg
      edema. PLMT is a rare and debilitating disorder characterized by lower limb pain
      and involuntary toes or feet movements. Its pathophysiology remains unknown and
      its therapy refractory to most drugs, except for pregabalin, as shown in this
      case series. PLMT is a rare and incapacitating syndrome due to the lack of an
      effective pain therapy. We report three patients with PLMT who favorable
      responded to pregabalin. We propose pregabalin be considered in the management of
      PLMT. 

PMID- 25766347
TI  - Muckle-Wells syndrome in an Indian family associated with NLRP3 mutation.
AB  - Muckle-Wells syndrome (MWS) is a rare autosomal dominant disease that belongs to
      a group of hereditary periodic fever syndromes. It is part of the wider spectrum
      of the cryopyrin-associated periodic syndrome (CAPS) which has only rarely been
      described in non-Caucasian individuals. It is characterized by recurrent self
      limiting episodes of fever, urticaria, arthralgia, myalgia and conjunctivitis
      from childhood. Progressive sensorineural hearing loss and amyloidosis are two
      late complications. MWS is caused by gain of function mutations in the NLRP3
      gene, which encodes cryopyrin, a protein involved in regulating the production of
      proinflammatory cytokines. We report two patients with MWS in an Indian family
      associated with the p.D303N mutation in the NLRP3 gene. These findings promote
      awareness of these hereditary periodic fever syndromes as a cause for recurrent
      fevers from childhood in the Indian population.

PMID- 25766348
TI  - Hospital-acquired pneumonia due to Leclercia adecarboxylata in a neurosurgical
      centre.
AB  - Leclercia adecarboxylata, a gram-negative bacillus of the Enterobacteriaceae
      family, is an uncommonly identified human pathogen. The organism has been
      reported worldwide and isolated from various environmental sources. Most human
      infections are polymicrobial and commonly occur in immunocompromised hosts,
      although nosocomial infections in immunocompetent hosts have been documented. We
      describe three case reports of L. adecarboxylata isolation from cases of hospital
      acquired pneumonia admitted to a tertiary care center for neurosurgical care.

PMID- 25766349
TI  - Primary renal primitive neuroectodermal tumor.
AB  - Primitive Neuroectodermal Tumor of the kidney is a rare entity. Very few cases of
      primary renal PNET have been reported to date. Most literature about rPNET is
      isolated case reports. We report a case of rPNET in a 39-year-old male with a pre
      operative diagnosis of renal cell carcinoma with renal vein thrombosis. The
      patient underwent radical nephrectomy with thrombolectomy, and histopathological
      examination revealed a highly aggressive tumor composed of monotonous sheets of
      round cells. Tumor cells were positive for CD 99 and FLI-1, hence confirming the
      diagnosis of Primitive Neuroectodermal Tumor. Post-surgery, patient was given
      VAC/IE-based adjuvant chemotherapy. In view of highly aggressive nature of this
      tumor, prompt diagnosis and imparting effective chemotherapy regimen to the
      patient is required, and it is important to differentiate PNET from other small
      round-cell tumors because of different therapeutic approach. 

PMID- 25766350
TI  - Systemic lupus erythematosus presenting as acute lupus pneumonitis in a young
      female.
AB  - Acute lupus pneumonitis is a rare initial presentation of systemic lupus
      erythematosus (SLE). We report a 19-year-old female presenting with fever and
      recurrent hemoptysis with radiological evidence of parenchymal lung involvement
      with mild pleural effusion. Subsequent development of malar and discoid rash with
      anti-nuclear antibodies (ANA) and anti-dsDNA positivity clinched the diagnosis.
      Her clinical signs and symptoms resolved with a course of intravenous pulse
      methyl-prednisolone along with radiological resolution. 

PMID- 25766351
TI  - Mycobacterium abscessus: causing fatal endocarditis after cardiac
      catheterization.
AB  - Mycobacterium abscessus is an unusual cause of infection in immunocompetent
      patients. The intrinsic and acquired resistance of this organism to multiple
      antibiotics is a major issue in planning treatment regimens. We report a case of
      M. abscessus endocarditis of the native aortic valve in an immunocompetent
      patient following coronary angiography with a fatal outcome. The case highlights
      an unfortunate intervention-related nosocomial infection and the difficulties in
      chemotherapeutic options for this organism, particularly in the presence of renal
      failure.

PMID- 25766352
TI  - A case of intestinal MALToma with co-existent tuberculosis and Peutz-Jeghers
      polyp.
AB  - A 22-year-old male patient underwent a segmental resection of the ileum due to
      clinical symptoms of bowel obstruction and radiological evidence of ileal wall
      thickening and enlarged mesenteric nodes. Histopathological examination of the
      resected specimen revealed an extranodal marginal zone B-cell lymphoma(MALToma)
      of the intestine and tuberculous lesions along with a solitary Peutz-Jeghers
      polyp. The case is presented for its rarity and to stress upon the clinical and
      radiological challenges that arise when lymphomas and tuberculous lesions co
      exist at the same site. 

PMID- 25766353
TI  - Development of chronic myelogenous leukemia in a case of chronic lymphocytic
      leukemia with Tp53 gene deletion.

PMID- 25766354
TI  - Nodular granular muscle degeneration of the appendix and obesity.

PMID- 25766355
TI  - The peculiar case of a blue man.

PMID- 25766356
TI  - A novel option for treatment of primary axillary hyperhidrosis: fractionated
      microneedle radiofrequency.

PMID- 25766357
TI  - Nasal conidiobolomycosis: a successful treatment option for localized disease.

PMID- 25766358
TI  - Comment on the article "Outcome of surgically treated octogenarians with breast
      cancer".

PMID- 25766359
TI  - Offender: virus or parasite or both.

PMID- 25766360
TI  - Longitudinal extensive transverse myelitis due to tuberculosis: a report of four
      cases.

PMID- 25766361
TI  - Relatives' experiences in acute care settings: barriers and remedial measures.

PMID- 25766362
TI  - Establishing correlation between genetics and nonresponse.

PMID- 25766363
TI  - A clinical, histopathologic, and outcome study of melanonychia striata in
      childhood.
AB  - BACKGROUND: The current literature suggests that approximately 5% to 10% of
      melanonychia striata cases in adults are the result of subungual melanoma.
      OBJECTIVE: We sought to evaluate the clinical and histopathologic features and to
      determine the outcomes and causes of melanonychia striata in a cohort of
      children. METHODS: We assessed 30 childhood cases of melanonychia striata for
      features typically associated with melanoma such as Hutchinson sign, width of the
      pigmented band, evolution, color, and nail dystrophy. We assessed the
      histopathology of lesional biopsy specimens, including melanocyte counts and
      suprabasal movement of melanocytes. Clinical follow-up information was reviewed
      when available. RESULTS: Histopathologic diagnoses included subungual lentigo in
      20 cases, subungual nevus in 5 cases, and atypical melanocytic hyperplasia in 5
      cases. Although a number of cases exhibited worrisome clinical or histopathologic
      features, none showed evidence of aggressive behavior or warranted a diagnosis of
      melanoma. LIMITATIONS: The sample size and follow-up times are limited.
      CONCLUSIONS: Melanonychia striata is typically associated with benign stable
      melanocytic proliferations in childhood. The overwhelming majority of cases can
      be managed conservatively. Biopsy is required in select cases.

PMID- 25766364
TI  - Reticular infantile hemangiomas with minimal or arrested growth associated with
      lipoatrophy.
AB  - BACKGROUND: Reticular infantile hemangioma (RIH) with minimal or arrested growth
      (MAG) is an underrecognized variant of infantile hemangioma (IH). OBJECTIVE: We
      describe a new clinical subtype of RIH-MAG associated with lipoatrophy. METHODS:
      The medical charts and serial clinical photographs and imaging studies of 53
      children given a diagnosis between 2004 and 2013 labeled as "abortive," "minimal
      or arrested growth," "reticular," or "congenital" hemangiomas were reviewed in
      the departments of dermatology and infantile plastic surgery of 2 French
      university hospital centers. RESULTS: Seven children were identified with RIH-MAG
      associated with lipoatrophy. There were 3 main patterns: (1) a focal cutaneous
      depression; (2) semicircular lipoatrophy with a horizontal bandlike depression;
      and (3) segmental soft-tissue atrophy. One case of segmental RIH-MAG of the back
      of the foot was associated with genital abnormalities reminiscent of perineal
      hemangioma, external genitalia malformations, lipomyelomeningocele, vesicorenal
      abnormalities, imperforate anus, and skin tags (PELVIS) syndrome. LIMITATIONS:
      The limitations were the retrospective study design, the small number of cases,
      and selection bias based on recall and photography. CONCLUSION: RIH-MAG with
      lipoatrophy is an uncommon variant of IH that may be confused with other vascular
      anomalies, particularly capillary malformation, focal and atrophic cutis
      marmorata congenita telangiectatica, and rapidly involuting congenital hemangioma
      with lipoatrophy as a sequela.

PMID- 25766365
TI  - Unified model of hyperthermia via hysteresis heating in systems of interacting
      magnetic nanoparticles.
AB  - We present a general study of the frequency and magnetic field dependence of the
      specific heat power produced during field-driven hysteresis cycles in magnetic
      nanoparticles with relevance to hyperthermia applications in biomedicine.
      Employing a kinetic Monte-Carlo method with natural time scales allows us to go
      beyond the assumptions of small driving field amplitudes and negligible inter
      particle interactions, which are fundamental to the applicability of the standard
      approach based on linear response theory. The method captures the
      superparamagnetic and fully hysteretic regimes and the transition between them.
      Our results reveal unexpected dipolar interaction-induced enhancement or
      suppression of the specific heat power, dependent on the intrinsic statistical
      properties of particles, which cannot be accounted for by the standard theory.
      Although the actual heating power is difficult to predict because of the effects
      of interactions, optimum heating is in the transition region between the
      superparamagnetic and fully hysteretic regimes. 

PMID- 25766367
TI  - Angiomatous meningioma in Sturge-Weber syndrome.
AB  - We report a case of an intraventricular angiomatous meningioma arising in a 3
      year-old boy diagnosed with Sturge-Weber syndrome (SWS) who presented with
      intractable epilepsy and right-sided hemiparesis. He underwent surgical resection
      of the epileptogenic focus. Histologic sections showed the typical findings of
      SWS accompanied by adjacent mild focal cortical dysplasia (International League
      Against Epilepsy Type Ib pattern; Palmini et al. Type IA). A small
      intraventricular mass, which was incidentally noted on imaging studies, was also
      excised. The mass showed a prominent venous vasculature with intermixed
      meningothelial cells, consistent with an angiomatous meningioma World Health
      Organization Grade I. SWS is a rare, sporadically occurring disorder marked by a
      port wine stain (hemangioma of the skin) arising in the distribution of the
      trigeminal nerve accompanied by an angiomatous proliferation in the
      leptomeninges. The underlying cortex often shows prominent dystrophic
      mineralization and gliosis. Patients often present with seizures and may require
      surgical resection when seizures prove to be pharmacoresistant. Meningiomas in
      SWS are a rare occurrence (only one known previously reported case) and
      angiomatous meningioma in SWS has never been described. The literature is briefly
      reviewed and the pathogenesis of hemangiomas in SWS and its implication in
      angiomatous meningioma is discussed. 

PMID- 25766366
TI  - Best evidence in multimodal pain management in spine surgery and means of
      assessing postoperative pain and functional outcomes.
AB  - Multimodal approaches to pain management have arisen with the goal of improving
      postoperative pain and reducing opioid analgesic use. We performed a
      comprehensive literature review to determine grades of recommendation for
      commonly used agents in multimodal pain management and provide a best practice
      guideline. To evaluate common drugs used in multimodal treatment of pain, a
      search was performed on English language publications on Medline (PubMed;
      National Library of Medicine, Bethesda, MD, USA). Manuscripts were rated as Level
      I-V according to the North American Spine Society's (NASS) standardized levels of
      evidence tables. Grades of recommendation were assigned for each drug based on
      the NASS Clinical Guidelines for Multidisciplinary Spine Care. There is good
      (Grade A) evidence gabapentinoids, acetaminophen, neuraxial blockade and extended
      release local anesthetics reduce postoperative pain and narcotic requirements.
      There is fair (Grade B) evidence that preemptive analgesia and nonsteroidal anti
      inflammatory drugs (NSAID) result in reduced postoperative pain. There is
      insufficient and/or conflicting (Grade I) evidence that muscle relaxants and
      ketamine provide a significant reduction in postoperative pain or narcotic usage.
      There is fair (Grade B) evidence that short-term use of NSAID result in no long
      term reduction in bone healing or fusion rates. Comprehensive assessment of the
      effectiveness of perioperative pain control can be accomplished through the use
      of validated measures. Multimodal pain management protocols have consistently
      been demonstrated to allow for improved pain control with less reliance on
      opioids. There is good quality evidence that supports many of the common agents
      utilized in multimodal therapy, however, there is a lack of evidence regarding
      optimal postoperative protocols or pathways. 

PMID- 25766368
TI  - Hirayama disease.
AB  - This article discusses three patients with likely Hirayama disease. They have no
      other significant past medical history and no personal or family history of other
      neurological disorders. Hirayama disease is a form of cervical myelopathy
      attributed to forward displacement of the posterior cervical dural sac on neck
      flexion with resultant cord compression and/or venous congestion. It is
      characterized by a pure motor focal amyotrophy in the distribution of C7, C8 and
      T1 spinal segmental-innervated muscles and differs from other motor neuron
      diseases by virtue of its ultimately non-progressive course. 

PMID- 25766370
TI  - Complete information acquisition in dynamic force microscopy.
AB  - Scanning probe microscopy has emerged as a primary tool for exploring and
      controlling the nanoworld. A critical part of scanning probe measurements is the
      information transfer from the tip-surface junction to the measurement system.
      This process reduces responses at multiple degrees of freedom of the probe to
      relatively few parameters recorded as images. Similarly, details of dynamic
      cantilever response at sub-microsecond time scales, higher-order eigenmodes and
      harmonics are lost by transitioning to the millisecond time scale of pixel
      acquisition. Hence, information accessible to the operator is severely limited,
      and its selection is biased by data processing methods. Here we report a
      fundamentally new approach for dynamic Atomic Force Microscopy imaging based on
      information-theory analysis of the data stream from the detector. This approach
      allows full exploration of complex tip-surface interactions, spatial mapping of
      multidimensional variability of material's properties and their mutual
      interactions, and imaging at the information channel capacity limit. 

PMID- 25766369
TI  - Regulation of matrix remodelling phenotype in gingival fibroblasts by substratum
      topography.
AB  - Gingival connective tissue often has a composition resembling that of scar
      surrounding dental implant abutments. Increased cell adhesion, alpha-smooth
      muscle actin (alpha-SMA) expression and increased extracellular matrix deposition
      are a hallmark of fibrotic cells, but how topographic features influence gingival
      fibroblast adhesion and adoption of the alpha-SMA positive myofibroblast
      phenotype associated with scarring is unknown. The purpose of the present study
      was to demonstrate whether implant topographies that limit adhesion formation
      would reduce myofibroblast differentiation and extracellular matrix deposition.
      Human gingival fibroblasts were cultured on PT (smooth) and SLA (roughened)
      titanium discs for varying time-points. At 1 and 2 weeks after seeding,
      incorporation of alpha-SMA into stress-fibre bundles and fibronectin deposition
      was significantly higher on PT than SLA surfaces indicating differentiation of
      the cells towards a myofibroblast phenotype. Analysis of adhesion formation
      demonstrated that cells formed larger adhesions and more stable adhesions on PT,
      with more nascent adhesions observed on SLA. Gene expression analysis identified
      up-regulation of 15 genes at 24 hrs on SLA versus PT associated with matrix
      remodelling. Pharmacological inhibition of Src/FAK signalling in gingival
      fibroblasts on PT reduced fibronectin deposition and CCN2 expression. We conclude
      that topographical features that reduce focal adhesion stability could be applied
      to inhibit myofibroblast differentiation in gingival fibroblasts. 

PMID- 25766371
TI  - Coumarin benzothiazole derivatives as chemosensors for cyanide anions.
AB  - Four coumarin benzothiazole derivatives, N-(benzo[d]thiazol-2-yl)-2-oxo-2H
      chromene-3-carboxamide (1), (Z)-N-(3-methylbenzo[d]thiazol-2(3H)-ylidene)-2-oxo
      2H-chromene-3-carboxamide (2), 7-(diethylamino)-N-(benzo[d]thiazol-2-yl)-2-oxo-2H
      chromene-3-carboxamide (3) and (Z)-7-(diethylamino)-N-(3-methylbenzo[d]thiazol
      2(3H)-ylidene)-2-oxo-2H-chromene-3-carboxamide) (4), have been synthesized. Their
      crystal structures, photophysical properties in acetonitrile and recognition
      properties for cyanide anions have been investigated. All the compounds are
      generally planar, especially compound 1 exhibits perfect planarity with dihedral
      angle between benzothiazolyl group and coumarin group being only 3.63 degrees .
      Coumarin benzothiazole compounds 1 and 3 can recognize cyanide anions by Michael
      addition reaction and compound 3 exhibits color change from yellow to colorless
      and green fluorescence was quenched completely, which can be observed by naked
      eye. Coumarin benzothiazolyliden compound 4 can recognize cyanide anions with
      fluorescence turn-on response based on the copper complex ensemble displacement
      mechanism. 

PMID- 25766372
TI  - Exploring the chemical bonding, infrared and UV-vis absorption spectra of OH
      radicals adsorption on the smallest fullerene.
AB  - In the present work, the density-functional theory calculations were performed on
      C20 hydroxylated fullerene. B3LYP functionals with 6-31G(d,p) basis set were
      utilized to gain insight into the bonding characters and intramolecular
      interactions of hydroxyl groups adsorbed on the cage. Interestingly, we observed
      that the C20 cage has the bonding patterns with spherical orbitals configuration
      [1S(2)1P(6)1D(10)1F(2)], and the adsorbed hydroxyl groups significantly affect
      the chemical bonding of the cage surface. Analysis of vertical electron
      affinities and vertical ionization potentials indicates that the polyhydroxylated
      derivative with eight hydroxyl groups is more stable than others. The
      intramolecular interaction of these derivatives considered here reveals that the
      more the hydroxyl groups in derivatives, the stronger the interaction in
      stabilizing structures. On the basis of theoretical studies, the hydroxyl groups
      largely enhance the infrared intensities, especially for the polyhydroxylated
      derivatives. 

PMID- 25766373
TI  - [Inadequate management of a difficult airway. Case SENSAR of the trimester].
AB  - A clinical case reported to SENSAR is presented (www.sensar.org). A patient came
      to the operating room for surgery for parathyroidectomy. She had several
      predictors of difficult airway management, including a story of difficulties in
      previous intubations in other hospitals, as the patient reported. Therefore,
      after evaluation in preoperative consultation, fibreoptic bronchoscopy intubation
      was recommended. The day of surgery after induction of general anesthesia direct
      laryngoscopy was performed, without recognizing any glottic structure (Cormack
      Lehane grade iv). Conventional laryngoscope was changed to a videolaryngoscope
      (Airtraq((r))) to try to improve the laryngoscopic view, but there were
      difficulties with handling and insertion of it, causing minor injuries to the
      lingual mucosa. Finally, tracheal intubation was achieved after several attempts.
      Analysis of the incident revealed the active error due to lack of experience of
      the professional who performed intubation maneuvers, favored by latent factors or
      contributors as were the complex pathology of the patient and the absence of
      protocols to difficult airway management in the hospital. Communication and
      analysis of this incident served to highlight the importance of the security
      protocols in Anesthesia, and as a result a working group that conducted the
      current algorithm approach to a difficult airway management was formed,
      established guidelines for further information patient and deals since clinical
      training and professional practice for the management of airway devices
      availables in the hospital. 

PMID- 25766374
TI  - A Content Analysis of Infant and Toddler Food Advertisements in Taiwanese Popular
      Pregnancy and Early Parenting Magazines.
AB  - BACKGROUND: Mothers who are exposed to formula advertisements (ads) are less
      likely to initiate breastfeeding and more likely to breastfeed for a shorter
      duration than other mothers. OBJECTIVE: The purpose of this study was to examine
      infant and toddler food ads in pregnancy and early parenting magazines. METHODS:
      A content analysis of infant and toddler food ads printed in 12 issues of 4
      magazines published in 2011 was performed. Coding categories of ads included
      product category, advertisement category, marketing information, and advertising
      appeal. The target age and health-related message of each product were coded.
      RESULTS: The researchers identified 756 infant and toddler food ads in the
      magazines. Compared with complementary food ads, formula product ads used more
      marketing strategies such as antenatal classes and baby contests to influence
      consumers and promote products. Nutritional quality and child health benefits
      were the two most frequently used advertising appeals. In addition, this study
      identified 794 formula products and 400 complementary food products; 42.8% of the
      complementary food products were intended for 4-month-old infants. Furthermore,
      91.9% of the ads for formula products and 81% of the ads for complementary food
      products contained claims concerning health function or nutrient content.
      CONCLUSIONS: Taiwanese pregnancy and early parenting magazines contain numerous
      infant and toddler food ads. These ads generally use health-related claims
      regarding specific nutrient content and health functions to promote infant and
      toddler foods. Health professionals should provide more information to parents on
      the differences between breast milk and formula milk, and they should be aware of
      the potential effect of infant and toddler food ads on parents' infant feeding
      decisions.

PMID- 25766376
TI  - Preface.

PMID- 25766377
TI  - Comment on: Comparison of the effects of Roux-en-Y gastrojejunostomy and LRYGB
      with small stomach pouch on type 2 diabetes mellitus in patients with BMI<35
      kg/m(2).

PMID- 25766375
TI  - Future technology insight: mass spectrometry imaging as a tool in drug research
      and development.
AB  - In pharmaceutical research, understanding the biodistribution, accumulation and
      metabolism of drugs in tissue plays a key role during drug discovery and
      development. In particular, information regarding pharmacokinetics,
      pharmacodynamics and transport properties of compounds in tissues is crucial
      during early screening. Historically, the abundance and distribution of drugs
      have been assessed by well-established techniques such as quantitative whole-body
      autoradiography (WBA) or tissue homogenization with LC/MS analysis. However, WBA
      does not distinguish active drug from its metabolites and LC/MS, while highly
      sensitive, does not report spatial distribution. Mass spectrometry imaging (MSI)
      can discriminate drug and its metabolites and endogenous compounds, while
      simultaneously reporting their distribution. MSI data are influencing drug
      development and currently used in investigational studies in areas such as
      compound toxicity. In in vivo studies MSI results may soon be used to support new
      drug regulatory applications, although clinical trial MSI data will take longer
      to be validated for incorporation into submissions. We review the current and
      future applications of MSI, focussing on applications for drug discovery and
      development, with examples to highlight the impact of this promising technique in
      early drug screening. Recent sample preparation and analysis methods that enable
      effective MSI, including quantitative analysis of drugs from tissue sections will
      be summarized and key aspects of methodological protocols to increase the
      effectiveness of MSI analysis for previously undetectable targets addressed.
      These examples highlight how MSI has become a powerful tool in drug research and
      development and offers great potential in streamlining the drug discovery
      process. 

PMID- 25766378
TI  - An efficient computational model to predict protonation at the amide nitrogen and
      reactivity along the C-N rotational pathway.
AB  - N-Protonation of amides is critical in numerous biological processes, including
      amide bonds proteolysis and protein folding as well as in organic synthesis as a
      method to activate amide bonds towards unconventional reactivity. A computational
      model enabling prediction of protonation at the amide bond nitrogen atom along
      the C-N rotational pathway is reported. Notably, this study provides a blueprint
      for the rational design and application of amides with a controlled degree of
      rotation in synthetic chemistry and biology. 

PMID- 25766380
TI  - Understanding the conductive channel evolution in Na:WO(3-x)-based planar
      devices.
AB  - An ion migration process in a solid electrolyte is important for ion-based
      functional devices, such as fuel cells, batteries, electrochromics, gas sensors,
      and resistive switching systems. In this study, a planar sandwich structure is
      prepared by depositing tungsten oxide (WO(3-x)) films on a soda-lime glass
      substrate, from which Na(+) diffuses into the WO(3-x) films during the
      deposition. The entire process of Na(+) migration driven by an alternating
      electric field is visualized in the Na-doped WO(3-x) films in the form of
      conductive channel by in situ optical imaging combined with infrared spectroscopy
      and near-field imaging techniques. A reversible change of geometry between a
      parabolic and a bar channel is observed with the resistance change of the
      devices. The peculiar channel evolution is interpreted by a thermal-stress
      induced mechanical deformation of the films and an asymmetric Na(+) mobility
      between the parabolic and the bar channels. These results exemplify a typical ion
      migration process driven by an alternating electric field in a solid electrolyte
      with a low ion mobility and are expected to be beneficial to improve the
      controllability of the ion migration in ion-based functional devices, such as
      resistive switching devices.

PMID- 25766381
TI  - Asymmetric warming significantly affects net primary production, but not
      ecosystem carbon balances of forest and grassland ecosystems in northern China.
AB  - We combine the process-based ecosystem model (Biome-BGC) with climate change
      scenarios based on both RegCM3 model outputs and historic observed trends to
      quantify differential effects of symmetric and asymmetric warming on ecosystem
      net primary productivity (NPP), heterotrophic respiration (Rh) and net ecosystem
      productivity (NEP) of six ecosystem types representing different climatic zones
      of northern China. Analysis of covariance shows that NPP is significant greater
      at most ecosystems under the various environmental change scenarios once
      temperature asymmetries are taken into consideration. However, these differences
      do not lead to significant differences in NEP, which indicates that asymmetry in
      climate change does not result in significant alterations of the overall carbon
      balance in the dominating forest or grassland ecosystems. Overall, NPP, Rh and
      NEP are regulated by highly interrelated effects of increases in temperature and
      atmospheric CO2 concentrations and precipitation changes, while the magnitude of
      these effects strongly varies across the six sites. Further studies underpinned
      by suitable experiments are nonetheless required to further improve the
      performance of ecosystem models and confirm the validity of these model
      predictions. This is crucial for a sound understanding of the mechanisms
      controlling the variability in asymmetric warming effects on ecosystem structure
      and functioning. 

PMID- 25766382
TI  - Ask not what personalized medicine can do for you--ask what you can do for
      personalized medicine.
AB  - BACKGROUND: Personalized medicine (PM) aims to offer tailored health care to
      individuals on the basis of their genetic profile. This paper explores the types
      of behaviors and practices that citizens are expected to adopt under PM, examines
      whether such expectations are realistic, and proposes strategies that could
      support citizens in the adoption of these behaviors. METHODS: Recent reports from
      national and international medical organizations and funders of PM are reviewed
      to investigate the types of behaviors and practices that citizens are expected to
      adopt under PM. These behaviors are examined in light of the current knowledge
      regarding citizen involvement in health care. RESULTS: Under PM, citizens are
      expected to be much more educated, proactive, and engaged in their health care
      than under conventional medical models. Actualizing such behaviors and practices
      may, however, be difficult or even unattainable for some groups of citizens.
      CONCLUSIONS: Educating citizens in PM, as proposed in the reports, is important
      but may not suffice for the adoption of new behaviors and practices by a majority
      of citizens. Approaches taking into consideration the heterogeneity of
      backgrounds, abilities, and resources among citizens are needed and include
      modifying reimbursement and pricing mechanisms, diversifying research, and
      developing low-cost PM programs.

PMID- 25766384
TI  - Analysis of cerebrospinal fluid for xanthochromia versus modern computed
      tomography scanners in the diagnosis of subarachnoid haemorrhage: experience at a
      tertiary trauma referral centre.
AB  - BACKGROUND: Diagnosis of subarachnoid haemorrhage, a neurosurgical emergency in
      patients with headache remains a logistical challenge. The rationale of the
      traditional pathway of cerebrospinal fluid xanthochromia analysis following
      negative computed tomography head scans to exclude subarachnoid haemorrhage has
      been challenged by the increasing accuracy of modern computed tomography
      scanners. AIM: We set out to establish whether our xanthochromia service was
      adding value to the diagnostic pathway for subarachnoid haemorrhage or whether it
      was acting merely as a supportive test. METHOD: A retrospective audit of all
      cerebrospinal fluid requests received since the inception of Xanthochromia
      service at a tertiary trauma centre. Cases interpreted as being consistent with
      subarachnoid haemorrhage based on cerebrospinal fluid xanthochromia analysis were
      selected for in-depth review from the total number of cases. RESULTS: In total
      660 requests were received for cerebrospinal fluid xanthochromia between August
      2009 and July 2012. A total 28 of these were interpreted as being consistent with
      subarachnoid haemorrhage. Only 18 (64.3%) of requests were deemed appropriate as
      the clinical presentation in the remaining 10 (35.7%) was strongly suggestive of
      other causes of headache. A final clinical diagnosis of subarachnoid haemorrhage
      was made in 11 of the 18 patients who had cerebrospinal fluid xanthochromia
      requested appropriately. From these 11, five (45%) were deemed initially computed
      tomography negative and cerebrospinal fluid analysis led to final correct
      diagnosis of subarachnoid haemorrhage and appropriate surgical management.
      CONCLUSION: Despite improved computed tomography scanning technology,
      cerebrospinal fluid xanthochromia interpretation aids in the definitive diagnosis
      of subarachnoid haemorrhage. When requested appropriately cerebrospinal fluid
      xanthochromia analysis remains a vital service as results impact on clinical
      decision making, especially when computed tomography scan results are equivocal
      and is also important in later presenting patients when computed tomography
      accuracy decreases.

PMID- 25766383
TI  - A novel variant of aquaporin 3 is expressed in killifish (Fundulus heteroclitus)
      intestine.
AB  - Killifish (Fundulus heteroclitus) are euryhaline teleosts that are widely used in
      environmental and toxicological studies, and they are tolerant to arsenic, in
      part due to very low assimilation of arsenic from the environment. The mechanism
      of arsenic uptake by the intestine, a major route of arsenic uptake in humans is
      unknown. Thus, the goal of this study was to determine if aquaglyceroporins
      (AQPs), which transport water and other small molecules including arsenite across
      cell membranes, are expressed in the killifish intestine, and whether AQP
      expression is affected by osmotic stress. Through RT-PCR and sequence analysis of
      PCR amplicons, we demonstrated that the intestine expresses kfAQP3a and kfAQP3b,
      two previously identified variants, and also identified a novel variant of
      killifish AQP3 (kfAQP3c) in the intestine. The variants likely represent
      alternate splice forms. A BLAST search of the F. heteroclitus reference genome
      revealed that the AQP3 gene resides on a single locus, while an alignment of the
      AQP3 sequence among 384 individuals from eight population ranging from Rhode
      Island to North Carolina revealed that its coding sequence was remarkably
      conserved with no fixed polymorphism residing in the region that distinguishes
      these variants. We further demonstrate that the novel variant transports arsenite
      into HEK293T cells. Whereas kfAQP3a, which does not transport arsenite, was
      expressed in both freshwater (FW) and saltwater (SW) acclimated fish, kfAQP3b, an
      arsenic transporter, was expressed only in FW acclimated fish, and kfAQP3c was
      expressed only in SW acclimated fish. Thus, we have identified a novel, putative
      splice variant of kfAQP3, kfAQP3c, which transports arsenic and is expressed only
      in SW acclimated fish. 

PMID- 25766385
TI  - Cystatin C- and creatinine-based equations in the assessment of renal function in
      HIV-positive patients prior to commencing Highly Active Antiretroviral Therapy.
AB  - BACKGROUND: We evaluated the accuracy and precision of creatinine- and cystatin C
      based prediction equations for estimating glomerular filtration rate compared to
      measured glomerular filtration rate in an antiretroviral-naive human
      immunodeficiency virus population. METHODS: The study population consisted of 100
      treatment-naive HIV patients. Glomerular filtration rate was estimated using the
      Cockcroft-Gault, Modification of Diet in Renal Disease (MDRD) and Chronic Kidney
      Disease Epidemiology Collaboration (CKD-EPI) equations, as well as cystatin C
      based equations (CKD-EPIcystatin C, cystatin Cvan Deventer and CKD-EPIcombined))
      compared to (51)Cr-EDTA plasma clearance-measured glomerular filtration rate. We
      calculated percentage bias, standard deviation of the differences, accuracy
      within 15 and 30% of measured glomerular filtration rate and sensitivity and
      specificity for predicting measured glomerular filtration rate <60 mL/min/1.73
      m(2). RESULTS: Bias for all estimating glomerular filtration rate equations
      ranged from -9.4% to 38.4%. The CKD-EPIcombined without ethnicity correction
      factor equation had the least bias, 2.9% (-2.9 to 8.8). Bias was higher for the
      Modification of Diet in Renal Disease and CKD-EPI equation with the African
      American ethnicity factor (38.4 and 33.7%) than without (14.2 and 15.3%).
      Standard deviation of the differences ranged from 29.2% (CKD-EPIcombined without
      ethnicity factor) to 54.0% (Modification of Diet in Renal Disease with ethnicity
      factor). Accuracy within 30% of measured glomerular filtration rate ranged from
      78% for CKD-EPIcombined without ethnicity factor to 56.7% for the Cockcroft-Gault
      equation. Sensitivity for creatinine-based equations was less than 50% and for
      the CKD-EPIcystatin C equation was 75%. CONCLUSION: Sensitivity of creatinine
      based equations for predicting glomerular filtration rate was poor in this group
      of patients. The CKD-EPIcombined equation performed better than creatinine-based
      equations.

PMID- 25766386
TI  - Safety assessment and therapeutic efficacy of percutaneous microwave ablation
      therapy combined with percutaneous ethanol injection for hepatocellular carcinoma
      adjacent to the gallbladder.
AB  - OBJECTIVE: This study sought to evaluate the safety and efficacy of ultrasound
      guided (US-guided) percutaneous microwave (MW) ablation combined with
      percutaneous ethanol injection (PEI) to treat liver tumours adjacent to the
      gallbladder. MATERIALS AND METHODS: A total of 136 patients with hepatocellular
      carcinoma (HCC) adjacent to the gallbladder, who underwent ultra-sonographically
      guided percutaneous MW ablation, which was combined with PEI in 132 patients,
      were retrospectively assessed. The patient population characteristics, tumour
      features, local tumour progression and treatment were compared and analysed. The
      safety and efficacy of the therapy were assessed by clinical data and imaging in
      follow-up examinations. RESULTS: All patients were completely treated with two
      sessions; 120 patients underwent one session, 16 patients underwent two sessions.
      The primary technique was effective in 95.6% of the cases, according to the
      computed tomography (CT) or magnetic resonance imaging (MRI) in the one-month
      follow-up (132 of 138 sessions). PEI and other therapies were performed in the
      patients who had been incompletely treated (all six patients underwent PEI, and
      some underwent other therapies, including one transcatheter arterial
      chemoembolisation (TACE), one liver transplantation and two liver resections).
      There was a median follow-up period of 30.1 months and a range of 4 to 68 months.
      None of the patients had major complications. There were no treatment-related
      deaths. Twenty-six patients died of primary disease progression that was not
      directly attributable to MW ablation (19.1%, 26/136). Local tumour progression
      was noted in five patients (3.7%, 5/136), who had completely ablated tumours at
      follow-up. The patients with locally progressing tumours underwent additional
      therapy (three patients underwent PEI, one patient TACE, and one liver
      resection). CONCLUSION: Ultrasound-guided percutaneous MW ablation, in
      combination with percutaneous ethanol injection and thermal monitoring, is a safe
      and effective treatment for HCC adjacent to the gallbladder.

PMID- 25766388
TI  - Dynamics of carrying a load with a handle suspension.
AB  - Carrying loads with a compliant pole or backpack suspension can reduce the peak
      forces of the load acting on the body when the suspension natural frequency is
      tuned below the stepping frequency. Here we investigate a novel application for a
      load suspension that could be used to carry a load by hand, which is a common yet
      difficult method of load carriage and results in inherently asymmetric dynamics
      during load carriage. We hypothesize that the asymmetric dynamics of carrying a
      load in one hand will result in multiple locomotion frequency modes which can
      affect the forces of carrying a load with a handle suspension. We tested an
      adjustable-stiffness hand-held load suspension with four different natural
      frequency values while walking and running compared to a rigid handle. As
      expected, the peak forces acting on the body decrease compared to a rigid handle
      as the effective suspension stiffness decreases below the stepping frequency.
      However, the asymmetric dynamics of carrying a load with one hand introduce
      another frequency mode at half the stepping frequency which increases the peak
      forces acting on the body when the natural frequency of the handle is tuned near
      this frequency. We conclude that hand-held load suspensions should be designed to
      have a natural frequency below the half-stepping frequency of walking to minimize
      the peak forces and the musculoskeletal stress on the human body while carrying
      loads with one hand. 

PMID- 25766387
TI  - Temperature-sensitive liposome-mediated delivery of thrombolytic agents.
AB  - BACKGROUND: Clinical efficacy of thrombolytic drugs is limited by lack of
      specific delivery and requires large therapeutic doses which increase toxicity.
      Encapsulating these drugs in temperature-sensitive liposomes and applying
      hyperthermia to deliver thrombolytic agents locally to thrombus might
      theoretically favourably alter the therapeutic window. The objectives of this
      study were to formulate liposomes encapsulating thrombolytics and assess
      thrombolytic activity following hyperthermia. METHODS: Three liposome
      formulations were investigated: temperature-sensitive liposome (TSL, DPPC:DSPE
      PEG2000 (mol% 95:5)), low temperature-sensitive liposome (LTSL, DPPC:MSPC:DSPE
      PEG2000 (mol% 85.3:9.7:5)), and traditional temperature-sensitive liposome (TTSL,
      DPPC:HSPC:Chol:DSPE-PEG2000 (mol% 55:25:15:5)). To characterise temperature
      dependent release of high molecular weight cargo from each formulation,
      fluorescein-conjugated dextrans (70 kDa) were loaded and release was quantified
      via spectrophotometry. Staphylokinase (SAK), urokinase, and tissue-type
      plasminogen activator were also loaded individually into each liposome
      formulation. Leakage at 37  degrees C and release at 38-44  degrees C were
      quantified via chromogenic enzymatic activity assay. Clot lysis was evaluated by
      measuring mass of blood clots before and after thrombolytic liposome treatment.
      RESULTS: The LTSL formulation had optimal release characteristics with maximum
      release at 41.3  degrees C. Release of dextrans from LTSLs was observed to be
      11.5 +/- 1.5%, 79.7 +/- 1.6%, and 93.6 +/- 3.7% after 15 min in plasma at 37
      degrees , 39 degrees , and 41.3  degrees C, respectively. The SAK LTSL had the
      highest release/leakage ratio and demonstrated greater clot lysis. CONCLUSIONS:
      The SAK LTSL achieves significant clot lysis in vitro. When combined with local
      hyperthermia, the SAK LTSL potentially produces sufficient thrombolysis while
      minimising systemic side effects.

PMID- 25766389
TI  - Mechanical assessment of cervical remodelling in pregnancy: insight from a
      synthetic model.
AB  - During the gestation and the cervical remodelling, several changes occur
      progressively in the structure of the tissue. An increase in the hydration,
      disorganisation of collagen network and decrease in elasticity can be observed.
      The collagen structure disorganisation is particularly complex: collagen fibres
      turn thicker and more wavy as the gestation progresses in a transition from
      relatively straight fibres to wavy fibres, while pores between collagen fibres
      become larger and separated. Shear wave elastography is a promising but not yet
      fully understood tool to assess these structural changes and the cervix's ability
      to dilate. To this end, a numerical histo-mechanical model is proposed in the
      present study, which aims at linking variations in the microscopic histo
      biomechanical processes with shear wave propagation characteristics. Parametric
      simulations are carried out for a broad range of mechanical and geometrical
      parameters. Results show a direct relationship between the histological and
      morphological changes during pregnancy and the viscoelastic behaviour of the
      tissue.

PMID- 25766390
TI  - The sensitivity of cartilage contact pressures in the knee joint to the size and
      shape of an anatomically shaped meniscal implant.
AB  - Since meniscal geometry affects the cartilage contact pressures, it is essential
      to carefully define the geometry of the synthetic meniscal implant that we
      developed. Recently, six independent modes of size- and shape-related geometry
      variation were identified through 3D statistical shape modeling (SSM) of the
      medial meniscus. However, this model did not provide information on the
      functional importance of these geometry characteristics. Therefore, in this study
      finite element simulations were performed to determine the influence of
      anatomically-based meniscal implant size and shape variations on knee cartilage
      contact pressures. Finite element simulations of the knee joint were performed
      for a total medial meniscectomy, an allograft, the average implant geometry, six
      implant sizes and ten shape variations. The geometries of the allograft and all
      implant variations were based on the meniscus SSM. Cartilage contact pressures
      and implant tensile strains were evaluated in full extension under 1200N of axial
      compression. The average implant induced cartilage peak pressures intermediate
      between the allograft and meniscectomy and also reduced the cartilage area
      subjected to pressures >5MPa compared to the meniscectomy. The smaller implant
      sizes resulted in lower cartilage peak pressures and compressive strains than the
      allograft, yet high implant tensile strains were observed. Shape modes 2, 3 and 6
      affected the cartilage contact stresses but to a lesser extent than the size
      variations. Shape modes 4 and 5 did not result in changes of the cartilage stress
      levels. The present study indicates that cartilage contact mechanics are more
      sensitive to implant size than to implant shape. Down-sizing the implant resulted
      in more favorable contact mechanics, but caused excessive material strains.
      Further evaluations are necessary to balance cartilage contact pressures and
      material strains to ensure cartilage protection and longevity of the implant. 

PMID- 25766391
TI  - Comparison of the biomechanical tensile and compressive properties of
      decellularised and natural porcine meniscus.
AB  - Meniscal repair is widely used as a treatment for meniscus injury. However, where
      meniscal damage has progressed such that repair is not possible, approaches for
      partial meniscus replacement are now being developed which have the potential to
      restore the functional role of the meniscus, in stabilising the knee joint,
      absorbing and distributing stress during loading, and prevent early degenerative
      joint disease. One attractive potential solution to the current lack of meniscal
      replacements is the use of decellularised natural biological scaffolds, derived
      from xenogeneic tissues, which are produced by treating the native tissue to
      remove the immunogenic cells. The current study investigated the effect of
      decellularisation on the biomechanical tensile and compressive (indentation and
      unconfined) properties of the porcine medial meniscus through an experimental
      computational approach. The results showed that decellularised medial porcine
      meniscus maintained the tensile biomechanical properties of the native meniscus,
      but had lower tensile initial elastic modulus. In compression, decellularised
      medial porcine meniscus generally showed lower elastic modulus and higher
      permeability compared to that of the native meniscus. These changes in the
      biomechanical properties, which ranged from less than 1% to 40%, may be due to
      the reduction of glycosaminoglycans (GAG) content during the decellularisation
      process. The predicted biomechanical properties for the decellularised medial
      porcine meniscus were within the reported range for the human meniscus, making it
      an appropriate biological scaffold for consideration as a partial meniscus
      replacement. 

PMID- 25766393
TI  - Comparison of Histochemical Staining Methods and Correlation with Transient
      Elastography in Acute Hepatitis.
AB  - OBJECTIVE: To compare Masson's trichrome (MT), Sirius red (SR) and orcein
      staining in acute hepatitis (AH) and to correlate them with transient
      elastography (TE), a noninvasive method to assess hepatic fibrosis. METHODS: We
      evaluated liver stiffness by TE in a cohort of 34 consecutive patients and
      assessed MT-, SR- and orcein-stained biopsies using the METAVIR scoring system
      and digital image analysis (DIA). RESULTS: MT and SR both showed severe fibrosis
      (stage III-IV, DIA = 12.7%). Orcein showed absent or mild fibrosis (stage 0-II,
      DIA = 4.4%; p < 0.05). In 29/34 cases (85%), stiffness values were >12.5 kPa, in
      keeping with SR/MT but not with orcein results. CONCLUSIONS: Even though in AH
      true elastic fibrosis is typically absent or mild, TE shows elevated stiffness
      values, in keeping with SR/MT evaluations. If not properly evaluated in the
      clinical context, these results would lead to an overestimation of fibrosis.
      Orcein is the only staining able to evidence the absence of true elastic
      fibrosis, which is a typical feature of AH. This is the first study comparing
      different staining procedures performed on AH biopsies by DIA versus TE. (c) 2015
      S. Karger AG, Basel.

PMID- 25766392
TI  - NGS population genetics analyses reveal divergent evolution of a Lyme Borreliosis
      agent in Europe and Asia.
AB  - Borrelia bavariensis is a recently described agent of Lyme disease within the B.
      burgdorferi sensu lato species complex and exhibits a strong capacity for human
      pathogenicity. B. bavariensis strains are widely distributed in Eurasia spanning
      the distribution range of the tick vectors Ixodes persulcatus and I. ricinus. It
      has been suggested that B. bavariensis forms two populations, one of which arose
      through vector adaptation and geographic expansion. We have performed
      phylogenetic and population genetic analyses with next-generation sequencing data
      of 26 strains of B. bavariensis targeting the main linear chromosome and two
      plasmids (lp54, cp26). A very low number of single nucleotide polymorphisms
      (SNPs) was found in the European population and a deep branching pattern between
      European and Asian B. bavariensis was observed in all phylogenies. The results
      confirm the population structure of B. bavariensis and strongly support the
      hypothesis of clonal expansion of the European population of B. bavariensis. In
      addition, signals of positive selection identified in the populations further
      support the hypothesis that the European population of B. bavariensis likely
      underwent vector adaptation in its recent evolutionary history. Identified genes
      represent promising candidates for experimental vector adaptation studies. Thus,
      this species forms a very good model to study vector adaptation, which is known
      to play an important role in the geographic distribution of B. burgdorferi.
      Analysis of well known virulence determinants that are attributed to severity of
      clinical manifestation in B. burgdorferi s.s. revealed no variation within the
      European population of B. bavariensis, underlining the importance of including
      various Borrelia species into investigations that aim to understand the
      pathogenesis of Lyme disease agents. 

PMID- 25766394
TI  - Spectral tuning in the eyes of deep-sea lanternfishes (Myctophidae): a novel
      sexually dimorphic intra-ocular filter.
AB  - Deep-sea fishes possess several adaptations to facilitate vision where light
      detection is pushed to its limit. Lanternfishes (Myctophidae), one of the world's
      most abundant groups of mesopelagic fishes, possess a novel and unique visual
      specialisation, a sexually dimorphic photostable yellow pigmentation,
      constituting the first record of a visual sexual dimorphism in any non-primate
      vertebrate. The topographic distribution of the yellow pigmentation across the
      retina is species specific, varying in location, shape and size.
      Spectrophotometric analyses reveal that this new retinal specialisation differs
      between species in terms of composition and acts as a filter, absorbing maximally
      between 356 and 443 nm. Microspectrophotometry and molecular analyses indicate
      that the species containing this pigmentation also possess at least 2 spectrally
      distinct rod visual pigments as a result of a duplication of the Rh1 opsin gene.
      After modelling the effect of the yellow pigmentation on photoreceptor spectral
      sensitivity, we suggest that this unique specialisation acts as a filter to
      enhance contrast, thereby improving the detection of bioluminescent emissions and
      possibly fluorescence in the extreme environment of the deep sea. The fact that
      this yellow pigmentation is species specific, sexually dimorphic and isolated
      within specific parts of the retina indicates an evolutionary pressure to
      visualise prey/predators/mates in a particular part of each species' visual
      field.

PMID- 25766395
TI  - On exploration of geometrically constrained space by medicinal leeches Hirudo
      verbana.
AB  - Leeches are fascinating creatures: they have simple modular nervous circuitry yet
      exhibit a rich spectrum of behavioural modes. Leeches could be ideal blue-prints
      for designing flexible soft robots which are modular, multi-functional, fault
      tolerant, easy to control, capable for navigating using optical, mechanical and
      chemical sensorial inputs, have autonomous inter-segmental coordination and
      adaptive decision-making. With future designs of leech-robots in mind we study
      how leeches behave in geometrically constrained spaces. Core results of the paper
      deal with leeches exploring a row of rooms arranged along a narrow corridor. In
      laboratory experiments we find that rooms closer to ends of the corridor are
      explored by leeches more often than rooms in the middle of the corridor. Also, in
      series of scoping experiments, we evaluate leeches capabilities to navigating in
      mazes towards sources of vibration and chemo-attraction. We believe our results
      lay foundation for future developments of robots mimicking behaviour of leeches. 

PMID- 25766396
TI  - Trifluoromethylation-initiated remote cross-coupling of carbonyl compounds to
      form carbon-heteroatom/carbon bonds.
AB  - By involving the reversal of conventional reactivity expectations without
      external oxidants, we describe a novel and convenient protocol of remote cross
      coupling of carbonyl compounds with a series of common and simple nucleophiles.
      This cross-coupling is triggered by radical trifluoromethylation of alkenes,
      thereby achieving highly selective remote difunctionalization of alkenes and
      alpha-position of the carbonyl group for facile access to trifluoromethyl alpha
      halo- and alpha-cyanocarbonyl compounds. The reaction exhibits a broad substrate
      scope with excellent functionality tolerance and many different types of
      nucleophiles; further synthetic applicability of the obtained compounds proved to
      be suitable, thus showing great potential for synthetic utility. 

PMID- 25766397
TI  - Surprise within a meningioma: case report of signet ring cell carcinoma
      metastasis in a meningioma.

PMID- 25766398
TI  - Pancreatic polypeptide response to a mixed meal is blunted in pancreatic head
      cancer associated with diabetes mellitus.
AB  - INTRODUCTION: Pancreatic polypeptide (PP) is a hormone secreted by islet cells of
      the ventral pancreas. It has been proposed that a blunted PP response to a mixed
      meal can distinguish diabetes mellitus (DM) secondary to pancreatic disease from
      other types of DM. We performed a proof of concept study to determine if PP
      response to a mixed meal discriminates DM secondary to pancreatic cancer (PaCDM)
      from type 2 DM (T2DM). METHODS: We studied 18 subjects with new onset DM (PaCDM
      (n = 9) and T2DM (n = 9); matched for age and gender). Serum PP levels were
      measured at 0, 30, and 60 min following a mixed meal. Increases in PP levels from
      baseline were compared using the Wilcoxon test. RESULTS: In PaCDM the PP increase
      following a mixed meal was less than T2DM at 30 min (median 60.0%, IQR, 33.0
      119.8 vs. 134.5%, IQR, 117.5-265.9; p = 0.03), but statistically similar at 60
      min (median 55.8%, interquartile range (IQR) 23.7-121.5 vs. 100.0%, IQR, 47.7
      202.5; p = 0.17). In PaCDM subjects, the PP increase over baseline was smaller in
      those with a tumor located in the pancreatic head (n = 6) compared to the
      body/tail (n = 3) at 30 min (41.3% vs. 158.7%, p = 0.02) and at 60 min (37.4% vs.
      167.4%,p = 0.04). CONCLUSIONS: Subjects with PaCDM have a blunted PP response to
      a mixed meal compared to T2DM. However, the blunted PP response is only observed
      in those PaC subjects with a tumor located in the head of the pancreas.
      Confirmation in larger studies may suggest this could be used to aid screening
      for sporadic PaC.

PMID- 25766399
TI  - Influence of collagen source on fibrillar architecture and properties of
      vitrified collagen membranes.
AB  - Collagen vitrigel membranes are transparent biomaterials characterized by a
      densely organized, fibrillar nanostructure that show promise in the treatment of
      corneal injury and disease. In this study, the influence of different type I
      collagen sources and processing techniques, including acid-solubilized collagen
      from bovine dermis (Bov), pepsin-solubilized collagen from human fibroblast cell
      culture (HuCC), and ficin-solubilized collagen from recombinant human collagen
      expressed in tobacco leaves (rH), on the properties of the vitrigel membranes was
      evaluated. Postvitrification carbodiimide crosslinking (CX) was also carried out
      on the vitrigels from each collagen source, forming crosslinked counterparts
      BovXL, HuCCXL, and rHXL, respectively. Collagen membrane ultrastructure and
      biomaterial properties were found to rely heavily on both collagen source and
      crosslinking. Bov and HuCC samples showed a random fibrillar organization of
      collagen, whereas rH vitrigels showed remarkable regional fibril alignment. After
      CX, light transmission was enhanced in all groups. Denaturation temperatures
      after CX increased in all membranes, of which the highest increase was seen in rH
      (14.71 degrees C), suggesting improved thermal stability of the collagen fibrils
      in the membranes. Noncrosslinked rH vitrigels may be reinforced through CX to
      reach levels of mechanical strength and thermal stability comparable to Bov.

PMID- 25766400
TI  - Leveraging state cancer registries to measure and improve the quality of cancer
      care: a potential strategy for California and beyond.
AB  - Despite recent increased attention to healthcare performance and the burden of
      disease from cancer, measures of quality of cancer care are not readily
      available. In 2013, the California HealthCare Foundation convened an expert
      workgroup to explore the potential for leveraging data in the California Cancer
      Registry (CCR), one of the world's largest population-based cancer registries,
      for measuring and improving the quality of cancer care. The workgroup assessed
      current registry operations, the value to be gained by linking CCR data with
      health insurance claims or encounter data and clinical data contained in health
      system electronic health records, and potential barriers to these linkages. The
      workgroup concluded that: 1) The CCR mandate should be expanded to include use of
      its data for quality of cancer care measurement and public reporting; and 2) a
      system should be developed to support linkage of registry data with both claims
      data and provider electronic health record data. 

PMID- 25766401
TI  - Re: a cancer theory kerfuffle can lead to new lines of research.

PMID- 25766402
TI  - Response.

PMID- 25766403
TI  - The role of C/EBP-beta LIP in multidrug resistance.
AB  - BACKGROUND: Chemotherapy triggers endoplasmic reticulum (ER) stress, which in
      turn regulates levels of the active (LAP) and the natural dominant-negative (LIP)
      forms of the transcription factor C/EBP-beta. LAP upregulates and LIP
      downregulates the multidrug resistance (MDR) protein P-glycoprotein (Pgp), but it
      is not known how critical is their role in establishing MDR. METHODS: Cell
      viability was quantitated by crystal violet staining and measuring absorbance at
      540nm. Expression of various proteins was determined by immunoblotting. mRNA
      levels were determined by quantitative reverse transcriptase polymerase chain
      reaction (RT-PCR). LIP and LAP were overexpressed using expression plasmids
      followed by selection with blasticidin. Tumor cells expressing doxycycline
      inducible LIP were orthotopically implanted in mice (n = 15 mice per group), and
      tumor size was measured daily by caliper. Tumor sections were stained with
      hematoxylin and eosin and immunostained for Pgp, proliferation, and ER stress
      markers. RESULTS: MDR cells do not express basal, chemotherapy-triggered, or ER
      stress-triggered LIP and fail to activate the CHOP-caspase-3 death-triggering
      axis upon ER stress or chemotherapy challenge. Overexpression of LIP reversed the
      MDR phenotype in vitro and in tumors implanted in mice. LIP was undetectable in
      MDR cells, probably due to its ubiquitination, which was 3.56-fold higher,
      resulting in lysosomal and proteasomal degradation of LIP. CONCLUSIONS:
      Spontaneous and drug-selected MDR cells lack LIP, which is eliminated by
      ubiquitin-mediated degradation. Loss of LIP drives MDR not only by increasing Pgp
      expression but also by a two-fold attenuation of ER stress-triggered cell death.

PMID- 25766406
TI  - Echocardiographic assessment of the cardiac amyloidoses.
AB  - Cardiac amyloidosis is a cardiomyopathy characterized by increased left
      ventricular (LV) wall thickness and normal or decreased LV cavity size.
      Congestive heart failure in cardiac amyloidosis is generally considered a
      predominantly diastolic phenomenon, with systolic dysfunction only occurring in
      late-stage disease. Echocardiography is a noninvasive, reproducible method of
      assessing cardiac features and function in cardiac amyloidosis, and some
      echocardiographic indices are prognostic for the amyloidoses, with M-mode and 2
      dimensional echocardiography able to detect increased LV wall thickness.
      Moreover, Doppler flow measurements can incrementally assess diastolic LV
      dysfunction, which is characteristic of cardiac amyloidosis, and provide
      important prognostic information. Additionally, tissue Doppler imaging can detect
      subtle changes in both systolic and diastolic LV function, which cannot be
      detected by Doppler flow measurements, and LV longitudinal strain assessed by
      color tissue Doppler and speckle tracking echocardiography can provide more
      accurate LV functional and prognostic information than tissue Doppler imaging.
      This review describes the advances in echocardiography and its crucial role in
      the diagnosis and management of cardiac amyloidosis.

PMID- 25766405
TI  - MiR-26a modulates extracellular matrix homeostasis in cartilage.
AB  - MicroRNAs (miRNAs) may represent new therapeutic targets for bone and joint
      diseases. We hypothesized that several cartilage-specific proteins are targeted
      by a single miRNA and used bioinformatics to identify a miRNA that can modulate
      extracellular matrix (ECM) homeostasis in cartilage. Bioinformatic analysis of
      miRNA binding sequences in the 3'-untranslated region (3'-UTR) of target genes
      was performed to identify a miRNA that could bind to the 3'-UTR of cartilage
      matrix-related genes. MiRNA expression was studied by quantitative PCR of
      microdissected growth plate cartilage and binding to the 3'-UTR sequences was
      analyzed by luciferase interaction studies. Levels of proteins encoded by target
      genes in cultures of miR-26a mimic- or inhibitor-transfected chondrocytes were
      determined by FACS or immunoblot analysis. The complementary binding sequence of
      miR-26a and miR-26b was found in the 3'-UTR of the prehypertrophic/hypertrophic
      specific genes Cd200, Col10a1 as well as Col9a1 and Ctgf. Both miRNAs were
      expressed in cartilage and only miR-26a was downregulated in hypertrophic growth
      plate cartilage. MiR-26a could interact with the 3'-UTR of Cd200 and Col10a1 in
      luciferase binding studies, but not with Col9a1 and Ctgf. However, protein
      expression of target genes and the ECM adaptor genes matrilin-3 and COMP was
      significantly altered in miR-26a mimic- or inhibitor-transfected chondrocytes,
      whereas the abundance of the cell surface receptor for insulin was not changed.
      In conclusion, miR-26a suppresses hypertrophic and ECM adaptor protein
      production. Dysregulation of miR-26a expression could contribute to ECM changes
      in cartilage diseases and this miRNA may therefore act as a therapeutic target. 

PMID- 25766404
TI  - Whole-exome sequencing identifies MDH2 as a new familial paraganglioma gene.
AB  - Disruption of the Krebs cycle is a hallmark of cancer. IDH1 and IDH2 mutations
      are found in many neoplasms, and germline alterations in SDH genes and FH
      predispose to pheochromocytoma/paraganglioma and other cancers. We describe a
      paraganglioma family carrying a germline mutation in MDH2, which encodes a Krebs
      cycle enzyme. Whole-exome sequencing was applied to tumor DNA obtained from a man
      age 55 years diagnosed with multiple malignant paragangliomas. Data were analyzed
      with the two-sided Student's t and Mann-Whitney U tests with Bonferroni
      correction for multiple comparisons. Between six- and 14-fold lower levels of
      MDH2 expression were observed in MDH2-mutated tumors compared with control
      patients. Knockdown (KD) of MDH2 in HeLa cells by shRNA triggered the
      accumulation of both malate (mean +/- SD: wild-type [WT] = 1+/-0.18; KD = 2.24+/
      0.17, P = .043) and fumarate (WT = 1+/-0.06; KD = 2.6+/-0.25, P = .033), which
      was reversed by transient introduction of WT MDH2 cDNA. Segregation of the
      mutation with disease and absence of MDH2 in mutated tumors revealed MDH2 as a
      novel pheochromocytoma/paraganglioma susceptibility gene. 

PMID- 25766407
TI  - Early detection of vulnerable atherosclerotic plaque for risk reduction of acute
      aortic rupture and thromboemboli and atheroemboli using non-obstructive
      angioscopy.
AB  - The mortality rate due to rupture of aortic dissection and aortic aneurysm is
      approximately 90%. Acute aortic rupture can be fatal prior to hospitalization and
      has proven difficult to diagnose correctly or predict. The in-hospital mortality
      rate of ruptured aortic aneurysm ranges from 53 to 66%. Emergency surgical and
      endovascular treatments are the only options for ruptured aortic dissection and
      aortic aneurysm. No method of systematic early detection or inspection of vessel
      injury is available at the prevention stage. Regardless of the improvement in
      many imaging modalities, aortic diameter has remained a major criterion for
      recommending surgery in diagnosed patients. Previous reports have suggested a
      relationship between vulnerable plaque and atherosclerotic aortic aneurysm. Non
      obstructive angioscopy is a new method for evaluating intimal injury over the
      whole aorta. It has been used to identify many advanced atherosclerotic plaques
      that were missed on traditional imaging modalities before aneurysm formation. Non
      obstructive angioscopy has shown that atherosclerosis of the aorta begins before
      that of the coronary artery, which had been noted on autopsy "in vivo". Strong or
      repetitive aortic injuries might cause sudden aortic disruption. Aortic atheroma
      is also a risk factor of stroke and perivascular embolism. Detecting aortic
      vulnerable atherosclerotic plaque on non-obstructive angioscopy may not only
      clarify the pathogenesis of acute aortic rupture and "aortogenic" thromboemboli
      and atheroemboli but also play a role in the pre-emptive medicine.

PMID- 25766408
TI  - The Evaluation of the Neutrophil-to-Lymphocyte Ratio in Coronary Chronic Total
      Occlusion.

PMID- 25766409
TI  - Thermodynamically neutral Kubas-type hydrogen storage using amorphous Cr(III)
      alkyl hydride gels.
AB  - In this paper we present amorphous chromium(III) hydride gels that show promise
      as reversible room temperature hydrogen storage materials with potential for
      exploitation in mobile applications. The material uses hydride ligands as a light
      weight structural feature to link chromium(III) metal centres together which act
      as binding sites for further dihydrogen molecules via the Kubas interaction, the
      mode of hydrogen binding confirmed by high pressure Raman spectroscopy. The best
      material possesses a reversible gravimetric storage of 5.08 wt% at 160 bar and 25
      degrees C while the volumetric density of 78 kgH2 m(-3) compares favourably to
      the DOE ultimate system goal of 70 kg m(-3). The enthalpy of hydrogen adsorption
      is +0.37 kJ mol(-1) H2 as measured directly at 40  degrees C using an isothermal
      calorimeter coupled directly to a Sieverts gas sorption apparatus. These data
      support a mechanism confirmed by computations in which the deformation enthalpy
      required to open up binding sites is almost exactly equal and opposite to the
      enthalpy of hydrogen binding to the Kubas sites, and suggests that this material
      can be used in on-board applications without a heat management system.

PMID- 25766411
TI  - Serum fibroblast growth factor 21 levels are increased in atrial fibrillation
      patients.
AB  - BACKGROUND: Fibroblast growth factor 21 (FGF-21), a newly discovered adipokine,
      plays an important role in glucose and lipid metabolism and is associated with
      the development of metabolic disorders, such as obesity, and cardiovascular
      diseases. This study aimed to investigate the association of serum FGF-21 levels
      with the presence of atrial fibrillation (AF). METHODS: Total 113 patients with
      AF and 60 healthy control subjects were enrolled. All AF cases were categorized
      into paroxysmal, persistent and permanent AF. Serum levels of FGF-21, high
      sensitivity C-reactive protein (hs-CRP) and other routine biochemical parameters
      were measured. RESULTS: Serum FGF-21 levels were significantly higher in AF
      patients than in controls (250.12+/-78.48 vs. 144.15+/-56.31pg/mL, P<0.001), and
      hs-CRP levels were significantly higher in AF patients than in controls (2.36+/
      1.10 vs. 1.24+/-0.82, P<0.05). In subgroup studies, patients with permanent AF
      had higher serum FGF-21 levels than those with persistent and paroxysmal AF.
      After the adjustment of the age, gender and body mass index, serum FGF-21 levels
      were positively correlated with left atrial diameter (LAD) (P<0.01). A
      multivariate logistic regression analysis showed that FGF-21, LAD and hs-CRP were
      correlated with AF (P<0.05). CONCLUSIONS: Our data demonstrate that serum FGF-21
      levels are elevated in AF patients and associated with atrial remolding,
      independent of established risk factors such as C-reactive protein.

PMID- 25766410
TI  - MitoCeption as a new tool to assess the effects of mesenchymal stem/stromal cell
      mitochondria on cancer cell metabolism and function.
AB  - Mitochondrial activity is central to tissue homeostasis. Mitochondria dysfunction
      constitutes a hallmark of many genetic diseases and plays a key role in tumor
      progression. The essential role of mitochondria, added to their recently
      documented capacity to transfer from cell to cell, obviously contributes to their
      current interest. However, determining the proper role of mitochondria in defined
      biological contexts was hampered by the lack of suitable experimental tools. We
      designed a protocol (MitoCeption) to directly and quantitatively transfer
      mitochondria, isolated from cell type A, to recipient cell type B. We validated
      and quantified the effective mitochondria transfer by imaging, fluorescence
      activated cell sorting (FACS) and mitochondrial DNA analysis. We show that the
      transfer of minute amounts of mesenchymal stem/stromal cell (MSC) mitochondria to
      cancer cells, a process otherwise occurring naturally in coculture, results in
      cancer cell enhanced oxidative phosphorylation (OXPHOS) activity and favors
      cancer cell proliferation and invasion. The MitoCeption technique, which can be
      applied to different cell systems, will therefore be a method of choice to
      analyze the metabolic modifications induced by exogenous mitochondria in host
      cells. 

PMID- 25766412
TI  - The recent escalation in strength of pyrethroid resistance in Anopheles coluzzi
      in West Africa is linked to increased expression of multiple gene families.
AB  - BACKGROUND: Since 2011, the level of pyrethroid resistance in the major malaria
      mosquito, Anopheles coluzzi, has increased to such an extent in Burkina Faso that
      none of the long lasting insecticide treated nets (LLINs) currently in use
      throughout the country kill the local mosquito vectors. We investigated whether
      this observed increase was associated with transcriptional changes in field
      caught Anopheles coluzzi using two independent whole-genome microarray studies,
      performed in 2011 and 2012. RESULTS: Mosquitoes were collected from south-west
      Burkina Faso in 2011 and 2012 and insecticide exposed or non-exposed insects were
      compared to laboratory susceptible colonies using whole-genome microarrays. Using
      a stringent filtering process we identified 136 genes, including the well-studied
      detoxification enzymes (p450 monoxygenases and esterases) and non-detoxification
      genes (e.g. cell transporters and cuticular components), associated with
      pyrethroid resistance, whose basal expression level increased during the
      timeframe of the study. A subset of these were validated by qPCR using samples
      from two study sites, collected over 3 years and marked increases in expression
      were observed each year. We hypothesise that these genes are contributing to this
      rapidly increasing resistance phenotype in An. coluzzi. A comprehensive analysis
      of the knockdown resistance (kdr) mutations (L1014S, L1014F and N1575Y) revealed
      that the majority of the resistance phenotype is not explained by target-site
      modifications. CONCLUSIONS: Our data indicate that the recent and rapid increase
      in pyrethroid resistance observed in south-west Burkina Faso is associated with
      gene expression profiles described here. Over a third of these candidates are
      also overexpressed in multiple pyrethroid resistant populations of An. coluzzi
      from neighbouring Cote d'Ivoire. This suite of molecular markers can be used to
      track the spread of the extreme pyrethroid resistance phenotype that is sweeping
      through West Africa and to determine the functional basis of this trait.

PMID- 25766413
TI  - Meta-analytic investigations of structural grey matter, executive domain-related
      functional activations, and white matter diffusivity in obsessive compulsive
      disorder: an integrative review.
AB  - Obsessive-compulsive disorder (OCD) is a debilitating disorder. However, existing
      neuroimaging findings involving executive function and structural abnormalities
      in OCD have been mixed. Here we conducted meta-analyses to investigate
      differences in OCD samples and controls in: Study 1 - grey matter structure;
      Study 2 - executive function task-related activations during (i) response
      inhibition, (ii) interference, and (iii) switching tasks; and Study 3 - white
      matter diffusivity. Results showed grey matter differences in the frontal,
      striatal, thalamus, parietal and cerebellar regions; task domain-specific neural
      differences in similar regions; and abnormal diffusivity in major white matter
      regions in OCD samples compared to controls. Our results reported concurrence of
      abnormal white matter diffusivity with corresponding abnormalities in grey matter
      and task-related functional activations. Our findings suggested the involvement
      of other brain regions not included in the cortico-striato-thalamo-cortical
      network, such as the cerebellum and parietal cortex, and questioned the
      involvement of the orbitofrontal region in OCD pathophysiology. Future research
      is needed to clarify the roles of these brain regions in the disorder. 

PMID- 25766414
TI  - Neurobiological and clinical variables associated with alcohol abuse in bulimia
      nervosa.
AB  - The study was aimed at analysing the reciprocal relationships of several clinical
      and neurobiological items in order to predict alcohol misuse in patients with
      bulimia nervosa (BN). Seventy BN patients and 70 healthy controls were assessed
      for depression, impulsivity, borderline personality traits and self-defeating
      behaviours using specific scales; serum cortisol and 24-hour urinary excretion of
      serotonin and 5-hydroxiindolacetic acid were also assessed. The study confirmed
      the implications of these clinical factors for alcohol misuse in BN patients, but
      the results suggested that depressive symptoms and hypercortisolism could lie
      behind these relationships.

PMID- 25766415
TI  - Long-term everolimus treatment of patients with pancreatic neuroendocrine tumors.
AB  - BACKGROUND/AIMS: Based on the significant prolongation of progression-free
      survival in a randomized phase III trial, RADIANT-3 (RAD001 in Advanced
      Neuroendocrine Tumors, Third Trial), everolimus has been approved for the
      management of advanced, progressive pancreatic neuroendocrine tumors (pNET).
      Here, we describe 15 participants in RADIANT-3 who were treated with everolimus
      at our study center. We report the long-term survival of a subset of patients.
      METHODS: Patients with advanced, progressive pNET were randomly assigned to the
      everolimus arm of RADIANT-3 or received everolimus as open-label treatment after
      experiencing progression on placebo or during the unblinded phase. RESULTS: Five
      patients on everolimus (5-10 mg/day) had stable disease for >43 to >76 months
      after initiating treatment. Three patients achieved stable disease for 19-25
      months, but died of progressive malignancy thereafter. Seven patients had stable
      disease for <=11 months after initiating everolimus therapy. CONCLUSION: Patients
      with advanced, progressive pNET can obtain long-term benefit from daily oral
      treatment with everolimus.

PMID- 25766417
TI  - Dutch police officers' preparation and performance of their arrest and self
      defence skills: a questionnaire study.
AB  - We investigated how Dutch police officers perceive their preparation for arrest
      and self-defence skills (ASDS) and their ability to manage violence on duty.
      Furthermore, we assessed whether additional experience (i.e., by having
      encountered violence on duty or by practicing martial arts) and self-perceived
      anxiety have an influence on these perceptions. Results of an online
      questionnaire (n = 922) showed that having additional experience was associated
      with self-perceived better performance. Officers who experience anxiety more
      often, on the other hand, reported more problems. Although most officers report
      sufficiently effective performance on duty, they, especially those with
      additional experience, feel that training frequency is too low and that the
      currently taught ASDS are only moderately usable (at least with the current
      amount of training). Based on the results, we suggest that increasing officers'
      ASDS experience, teaching officers to perform with high anxiety, or reconsidering
      the taught skills, may be necessary to further improve performance of police
      officers on duty.

PMID- 25766416
TI  - Influence of musculoskeletal pain on workers' ergonomic risk-factor assessments.
AB  - This study compares the ergonomic risk-factor assessments of workers with and
      without musculoskeletal pain. A questionnaire on the musculoskeletal pain
      experienced in various body regions during the 12 months and seven days preceding
      the data collection was administered to 473 workers from three industrial
      sectors. The Ergonomic Workplace Analysis method, developed by the Finnish
      Institute of Occupational Health (FIOH), was then used by the workers and an
      ergonomics expert to assess the workstations. The ergonomic quality of the
      workstations and the need for change were also assessed by the expert and the
      workers at the workstation, using visual analog scales (VAS). Results show that
      the workers in this study were exposed to significant musculoskeletal disorder
      (MSD) risk factors, according to the FIOH assessment and the high percentages of
      reported pain. The results also show that those who reported pain in the seven
      days prior to the assessment evaluated their workstations more negatively than
      subjects who reported no pain, while the expert found no difference between the
      two groups' exposure to MSD risk factors.

PMID- 25766418
TI  - Reduction in predicted survival times in cold water due to wind and waves.
AB  - Recent marine accidents have called into question the level of protection
      provided by immersion suits in real (harsh) life situations. Two immersion suit
      studies, one dry and the other with 500 mL of water underneath the suit, were
      conducted in cold water with 10-12 males in each to test body heat loss under
      three environmental conditions: calm, as mandated for immersion suit
      certification, and two combinations of wind plus waves to simulate conditions
      typically found offshore. In both studies mean skin heat loss was higher in wind
      and waves vs. calm; deep body temperature and oxygen consumption were not
      different. Mean survival time predictions exceeded 36 h for all conditions in the
      first study but were markedly less in the second in both calm and wind and waves.
      Immersion suit protection and consequential predicted survival times under
      realistic environmental conditions and with leakage are reduced relative to calm
      conditions.

PMID- 25766419
TI  - Driving performance and driver discomfort in an elevated and standard driving
      position during a driving simulation.
AB  - The primary purposes of a vehicle driver's seat, is to allow them to complete the
      driving task comfortably and safely. Within each class of vehicle (e.g.
      passenger, commercial, industrial, agricultural), there is an expected driving
      position to which a vehicle cabin is designed. This paper reports a study that
      compares two driving positions, in relation to Light Commercial Vehicles (LCVs),
      in terms of driver performance and driver discomfort. In the 'elevated' driving
      position, the seat is higher than usually used in road vehicles; this is compared
      to a standard driving position replicating the layout for a commercially
      available vehicle. It is shown that for a sample of 12 drivers, the elevated
      position did not, in general, show more discomfort than the standard position
      over a 60 min driving simulation, although discomfort increased with duration.
      There were no adverse effects shown for emergency stop reaction time or for
      driver headway for the elevated posture compared to the standard posture. The
      only body part that showed greater discomfort for the elevated posture compared
      to the standard posture was the right ankle. A second experiment confirmed that
      for 12 subjects, a higher pedal stiffness eliminated the ankle discomfort
      problem.

PMID- 25766420
TI  - Effects of wearing gumboots and leather lace-up boots on lower limb muscle
      activity when walking on simulated underground coal mine surfaces.
AB  - This study aimed to investigate the effects of wearing two standard underground
      coal mining work boots (a gumboot and a leather lace-up boot) on lower limb
      muscle activity when participants walked across simulated underground coal mining
      surfaces. Quadriceps (rectus femoris, vastus medialis, vastus lateralis) and
      hamstring (biceps femoris, semitendinosus) muscle activity were recorded as
      twenty male participants walked at a self-selected pace around a circuit while
      wearing each boot type. The circuit consisted of level, inclined and declined
      surfaces composed of rocky gravel and hard dirt. Walking in a leather lace-up
      boot, compared to a gumboot, resulted in increased vastus lateralis and increased
      biceps femoris muscle activity when walking on sloped surfaces. Increased muscle
      activity appears to be acting as a slip and/or trip prevention strategy in
      response to challenging surfaces and changing boot features. 

PMID- 25766421
TI  - The influence of gait cadence on the ground reaction forces and plantar pressures
      during load carriage of young adults.
AB  - Biomechanical gait parameters--ground reaction forces (GRFs) and plantar
      pressures--during load carriage of young adults were compared at a low gait
      cadence and a high gait cadence. Differences between load carriage and normal
      walking during both gait cadences were also assessed. A force plate and an in
      shoe plantar pressure system were used to assess 60 adults while they were
      walking either normally (unloaded condition) or wearing a backpack (loaded
      condition) at low (70 steps per minute) and high gait cadences (120 steps per
      minute). GRF and plantar pressure peaks were scaled to body weight (or body
      weight plus backpack weight). With medium to high effect sizes we found greater
      anterior-posterior and vertical GRFs and greater plantar pressure peaks in the
      rearfoot, forefoot and hallux when the participants walked carrying a backpack at
      high gait cadences compared to walking at low gait cadences. Differences between
      loaded and unloaded conditions in both gait cadences were also observed.

PMID- 25766422
TI  - The validity of the first and second generation Microsoft KinectTM for
      identifying joint center locations during static postures.
AB  - The KinectTM sensor released by Microsoft is a low-cost, portable, and marker
      less motion tracking system for the video game industry. Since the first
      generation Kinect sensor was released in 2010, many studies have been conducted
      to examine the validity of this sensor when used to measure body movement in
      different research areas. In 2014, Microsoft released the computer-used second
      generation Kinect sensor with a better resolution for the depth sensor. However,
      very few studies have performed a direct comparison between all the Kinect sensor
      identified joint center locations and their corresponding motion tracking system
      identified counterparts, the result of which may provide some insight into the
      error of the Kinect-identified segment length, joint angles, as well as the
      feasibility of adapting inverse dynamics to Kinect-identified joint centers. The
      purpose of the current study is to first propose a method to align the coordinate
      system of the Kinect sensor with respect to the global coordinate system of a
      motion tracking system, and then to examine the accuracy of the Kinect sensor
      identified coordinates of joint locations during 8 standing and 8 sitting
      postures of daily activities. The results indicate the proposed alignment method
      can effectively align the Kinect sensor with respect to the motion tracking
      system. The accuracy level of the Kinect-identified joint center location is
      posture-dependent and joint-dependent. For upright standing posture, the average
      error across all the participants and all Kinect-identified joint centers is 76
      mm and 87 mm for the first and second generation Kinect sensor, respectively. In
      general, standing postures can be identified with better accuracy than sitting
      postures, and the identification accuracy of the joints of the upper extremities
      is better than for the lower extremities. This result may provide some
      information regarding the feasibility of using the Kinect sensor in future
      studies.

PMID- 25766423
TI  - Effect of gait on formation of thermal environment inside footwear.
AB  - In this study, the relationship between the gait condition and foot temperature
      distributions inside footwear was investigated using subject experiments.
      Mechanical, physical, and physiological variables such as the foot contact force,
      landing speed, and metabolic heat generation were also measured. Gait motion
      measurements showed that a large contact force was concentrated in the small area
      of the heel at the initial contact and later at the forefoot. A faster gait
      produced a larger contact force, higher landing velocity, higher skin
      temperature, and larger metabolism during gait. The temperature at the bottom of
      the foot increased, and the temperature on the upper side decreased. The
      metabolic heat generation had a basic impact on the temperature profile, and skin
      temperatures tended to increase gradually. In addition, high-temperature
      elevation regions such as the big toe and heel coincided with regions with high
      contact loads, which suggested a relationship between the temperature elevation
      and contact load. 

PMID- 25766424
TI  - Partly visible periods in posture observation from video: prevalence and effect
      on summary estimates of postures in the job.
AB  - This paper investigated the extent to which observers rated clearly visible
      postures on video differently from partly visible postures, and whether
      visibility affected full-shift posture summaries. Trunk and upper arm postures
      were observed from 10,413 video frames representing 80 shifts of baggage
      handling; observers reported postures as fully or only partly visible. Postures
      were summarized for each shift into several standard metrics using all available
      data, only fully visible frames, or only partly visible frames. 78% of trunk and
      70% of upper arm postural observations were inferred. When based on all data,
      mean and 90th percentile trunk postures were 1.8 degrees  and 5.6 degrees  lower,
      respectively, than when based only on fully visible situations. For the arm;
      differences in mean and 90th percentile were 0.7 degrees  and 8.2 degrees . Daily
      posture summaries were significantly influenced by whether partly visible
      postures are included or not. 

PMID- 25766425
TI  - Intraoperative consultation on pediatric central nervous system tumors by squash
      cytology.
AB  - Squash cytology (SC) is a very useful procedure during neurosurgical
      intraoperative consultation (IOC), and it is especially recommended for the
      evaluation of soft tumors or tumors that are highly cellular (just the
      characteristics of pediatric central nervous system [CNS] tumors). The aim of
      this review is to familiarize pathologists with the range of cytomorphologic
      appearances that can occur during IOC for pediatric CNS tumors and with the
      diagnostic dilemmas and pitfalls encountered in this setting. This article is
      based on the medical literature and the authors' experience with a large series
      of cases accrued over a 12-year period at 3 institutions. SC is a specially
      recommended procedure in IOC for pediatric CNS tumors; it reveals the fine
      cellular details and background features in a manner not seen in corresponding
      frozen sections. Indeed, a differential diagnosis between histologically look
      alike processes can be achieved with more confidence if SC is employed.

PMID- 25766426
TI  - Tetraparesis and failure of pacemaker capture induced by severe hyperkalemia:
      case report and systematic review of available literature.
AB  - BACKGROUND: In severe hyperkalemia, neurologic symptoms are described more rarely
      than cardiac manifestations. We report a clinical case; present a systematic
      review of available literature on secondary hyperkalemic paralysis (SHP); and
      also discuss pathogenesis, clinical effects, and therapeutic options. CASE
      REPORT: A 75-year-old woman presented to the emergency department complaining of
      tetraparesis. Her serum potassium level was 11.4 mEq/L. Electrocardiogram (ECG)
      showed a pacemaker (PMK)-induced rhythm, with loss of atrial capture and wide QRS
      complexes. After emergency treatment to restore cell membrane potential threshold
      and lower serum potassium, neurologic and ECG signs completely disappeared. An
      acute myocardial infarction subsequently occurred, possibly linked to tachycardia
      induced by salbutamol therapy. We reviewed 99 articles (119 patients). Mean serum
      potassium was 8.8 mEq/L. In most cases, ECG showed the presence of tall T waves;
      loss of PMK atrial capture was documented in 5 patients. In 94 patients, flaccid
      paralysis was described and in 25, severe muscular weakness; in 65 patients,
      these findings were associated with other symptoms. Concurrent renal failure was
      often documented. The most frequent treatments were dialysis and infusion of
      insulin and glucose. Eighty-seven percent of patients had complete resolution of
      symptoms. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Severe
      hyperkalemia is always a life-threatening medical emergency, as it can
      precipitate fatal dysrhythmias and paralysis. SHP should be considered in the
      differential diagnosis of neurologic signs and symptoms of uncertain etiology,
      especially in a subject with kidney failure or who is taking medications that may
      worsen renal function. The presence of a PMK does not necessarily impede
      hyperkalemic cardiac toxicity.

PMID- 25766427
TI  - Use of quality improvement interventions and the link to performance on
      percutaneous intervention for acute myocardial infarction.
AB  - BACKGROUND: Despite numerous calls for hospitals to employ quality improvement
      (QI) interventions to improve emergency department (ED) performance, their impact
      has not been explored in multi-site investigations. OBJECTIVE: We investigated
      the association between use of QI interventions (patient flow strategies, ED
      electronic dashboards, and five-level triage systems) and hospital performance on
      receipt of percutaneous intervention (PCI) within 90 min for acute myocardial
      infarction patients, a publicly available quality measure. METHODS: This was an
      exploratory, cross-sectional analysis of secondary data from 292 hospitals. Data
      were drawn from the Quality Improvement Activities Survey, the American Hospital
      Association's Annual Survey, and Hospital Compare. Linear regression models were
      used to detect differences in PCI performance scores based on whether hospitals
      employed one or more QI interventions. RESULTS: Fifty-three percent of hospitals
      reported widespread use of patient flow strategies, 62% reported using a
      dashboard, and 74% reported using a five-level triage system. Time to PCI
      performance scores were 3.5 percentage points higher (i.e., better) for hospitals
      that used patient flow strategies and 6.2 percentage points higher for hospitals
      that used a five-level triage system. Scores were 10.4 percentage points higher
      at hospitals that employed two quality improvement interventions and 12.8
      percentage points higher at hospitals that employed three. CONCLUSION: Employing
      QI interventions was associated with better PCI scores. More research is needed
      to explore the direction of this relationship, but results suggest that hospitals
      should consider adopting patient flow strategies, electronic dashboards, and five
      level triage systems to improve PCI scores.

PMID- 25766429
TI  - New surgical approach for giant paraesophageal hernia repair: closure of the
      esophageal hiatus anteriorly using the left triangular ligament.
AB  - BACKGROUND: Obtaining a tension-free repair for giant paraesophageal hernias
      (PEH) is often challenging. Many different techniques have been proposed,
      including laparoscopic posterior hiatoplasty with the use of prosthetic or
      biologic mesh as well as the use of autologous teres or falciform ligament flaps.
      In this report, we describe the use of the left triangular ligament as an onlay
      autologous vascularized flap to bridge the anterior residual defect after
      posterior cruroplasty. METHODS: A novel technique of paraesophageal hiatal hernia
      repair is described. Posterior hiatoplasty is performed, including the
      approximation of the diaphragmatic crural fibers to the extent possible. The left
      triangular ligament is then mobilized and sutured to the right and left crural
      fibers lining the esophageal hiatus to seal the anterior residual diaphragmatic
      defect. RESULTS: This technique has been performed in 4 patients with a mean age
      of 71 years and a 3:1 female to male ratio. The average hiatal defect size was
      5.5 cm and the average length of operation was 122 min. There was no evidence of
      radiologic or clinical recurrence on follow-up. CONCLUSION: The use of the left
      triangular ligament flap is feasible and may be a valuable tool for closure of an
      anterior diaphragmatic defect in giant PEHs. Additional studies to validate its
      long-term function are needed.

PMID- 25766428
TI  - Critical role of Rgs19 in mouse embryonic stem cell proliferation and
      differentiation.
AB  - Mouse embryonic stem cells (ESCs) are self-renewing, pluripotent, and have the
      ability to differentiate into the three germ layers required to form all
      embryonic tissues. These properties are maintained by both intrinsic and
      extrinsic factors. Many studies have contributed to the understanding of the
      molecular signal transduction required for pluripotency and controlled
      differentiation. Such an understanding is important in the potential application
      of stem cells to cell therapy for disease, and thus there is an interest in
      understanding the cell cycle regulation, pluripotency, and differentiation of
      ESCs. The regulator of G protein signaling (RGS) family consists of over 20
      members. Rgs19, one such protein, specifically interacts with Galphai to enhance
      its GTPase activity. Growth factor receptors use Gi proteins for signal
      transduction, and Rgs19 may thus be involved in the regulation of cell
      proliferation. In a previous gain-of-function study, Rgs19 overexpression was
      found to enhance proliferation in various cell types. Our data demonstrate a role
      for Rgs19 in the regulation of ESC differentiation. Based on the presence of
      Rgs19 in ESCs, the morphological and molecular properties of wild-type and Rgs19
      +/- ESCs during LIF withdrawal, in vitro differentiation, and teratoma formation
      were compared. Our findings provide insight for the first time into the
      mechanisms involved in Rgs19 regulation of mouse ESC proliferation and
      differentiation. 

PMID- 25766430
TI  - Eruptive melanocytic nevi with satellite lesions following insulin treatment in a
      girl with type 1 diabetes mellitus.

PMID- 25766431
TI  - Interactions of PLGA nanoparticles with blood components: protein adsorption,
      coagulation, activation of the complement system and hemolysis studies.
AB  - The intravenous administration of poly(lactic-co-glycolic) acid (PLGA)
      nanoparticles has been widely reported as a promising alternative for delivery of
      drugs to specific cells. However, studies on their interaction with diverse blood
      components using different techniques are still lacking. Therefore, in the
      present work, the interaction of PLGA nanoparticles with blood components was
      described using different complementary techniques. The influence of different
      encapsulated compounds/functionalizing agents on these interactions was also
      reported. It is worth noting that all these techniques can be simply performed,
      without the need for highly sophisticated apparatus or skills. Moreover, their
      transference to industries and application of quality control could be easily
      performed. Serum albumin was adsorbed onto all types of tested nanoparticles. The
      saturation concentration was dependent on the nanoparticle size. In contrast,
      fibrinogen aggregation was dependent on nanoparticle surface charge. The
      complement activation was also influenced by the nanoparticle functionalization;
      the presence of a functionalizing agent increased complement activation, while
      the addition of an encapsulated compound only caused a slight increase. None of
      the nanoparticles influenced the coagulation cascade at low concentrations.
      However, at high concentrations, cationized nanoparticles did activate the
      coagulation cascade. Interactions of nanoparticles with erythrocytes did not
      reveal any hemolysis. Interactions of PLGA nanoparticles with blood proteins
      depended both on the nanoparticle properties and the protein studied. Independent
      of their loading/surface functionalization, PLGA nanoparticles did not influence
      the coagulation cascade and did not induce hemolysis of erythrocytes; they could
      be defined as safe concerning induction of embolization and cell lysis. 

PMID- 25766432
TI  - The serine protease inhibitor camostat mesilate attenuates the progression of
      chronic kidney disease through its antioxidant effects.
AB  - BACKGROUND/AIMS: We have so far demonstrated the renoprotective effect of
      camostat mesilate (CM) in 5/6 nephrectomized rats at least partly through its
      antioxidant effect. However, precise mechanisms were not fully clarified.
      Therefore, we now examined the renoprotective and antioxidant mechanisms of CM by
      using the adenine-induced chronic kidney disease (CKD) rat model. METHODS: In
      protocol 1, we analyzed the effect of CM on CKD. Rats were fed on a 0.75% adenine
      diet for 3 weeks to induce CKD followed by the experimental period with vehicle,
      CM, or hydralazine (HYD) treatment for 5 weeks. In protocol 2, we examined the
      safety of CM and HYD on the normal rats. In addition, we explored free radical
      scavenging activities of CM and its metabolites in vitro using electron
      paramagnetic resonance (EPR) spectroscopy. RESULTS: CM, but not HYD,
      significantly reduced the serum creatinine levels, although both treatments
      showed similar reduction in the blood pressure. CM decreased mRNA expression and
      protein levels of fibrotic markers, the severity of renal fibrosis, the
      accumulation of oxidative stress, and the expression of NADPH oxidase components
      in the kidney. In the protocol 2, there were no statistically significant
      differences in general parameters except for the systolic blood pressure in HYD
      group. EPR study revealed that CM and its metabolites have potent hydroxyl
      radical scavenging activities in vitro. CONCLUSION: Our findings indicate that CM
      significantly ameliorates the progression of CKD partly through its antioxidant
      effect independently from its blood pressure-lowering effect. Our results suggest
      the possibility that CM could be a new therapeutic agent that could arrest the
      progression of CKD.

PMID- 25766433
TI  - Enzymatic enantioselective decarboxylative protonation of heteroaryl malonates.
AB  - The enzyme aryl/alkenyl malonate decarboxylase (AMDase) catalyses the
      enantioselective decarboxylative protonation (EDP) of a range of disubstituted
      malonic acids to give homochiral carboxylic acids that are valuable synthetic
      intermediates. AMDase exhibits a number of advantages over the non-enzymatic EDP
      methods developed to date including higher enantioselectivity and more
      environmentally benign reaction conditions. In this report, AMDase and engineered
      variants have been used to produce a range of enantioenriched heteroaromatic
      alpha-hydroxycarboxylic acids, including pharmaceutical precursors, from readily
      accessible alpha-hydroxymalonates. The enzymatic method described here represents
      an improvement upon existing synthetic chemistry methods that have been used to
      produce similar compounds. The relationship between the structural features of
      these new substrates and the kinetics associated with their enzymatic
      decarboxylation is explored, which offers further insight into the mechanism of
      AMDase. 

PMID- 25766434
TI  - Inflammatory pseudotumour-like follicular dendritic cell tumour of the spleen.
AB  - We describe an unusual case of a 73-year-old woman presenting with a solitary
      splenic mass 8 cm in diameter and an elevation of serum soluble interleukin-2
      receptor level. The preoperative diagnosis was primary malignant lymphoma of the
      spleen. Splenectomy was conducted. Histological analysis confirmed an
      inflammatory pseudotumour-like follicular dendritic cell tumour that showed
      different clinicopathological features from those of the classic follicular
      dendritic cell tumour. Only 33 cases of inflammatory pseudotumour-like follicular
      dendritic cell tumour have so far been reported. We discuss the incidence,
      presentation and management of this rare disease.

PMID- 25766435
TI  - Triceps tendon rupture: an uncommon orthopaedic condition.
AB  - Triceps tendon disruption is a rare orthopaedic injury that can lead to poor
      outcomes if misdiagnosed or managed inappropriately. This case report illustrates
      the importance of early, precise diagnosis of triceps rupture by clinical and
      radiological examination with appropriate management. A weightlifter who had
      fallen while riding his bike presented with pain, swelling around the posterior
      aspect of the left arm just above the elbow. Physical examination revealed
      ecchymosis and weakness in elbow extension. A radiograph of the elbow showed a
      small fleck of bone proximal to the tip of the olecranon. The patient was
      initially stabilised. Early intervention in the form of primary tendon repair was
      performed within 3 days and rehabilitation was started. The patient improved
      significantly to his best possible functional status with Mayo elbow score of 85.
      Early intervention was the key to better prognosis.

PMID- 25766436
TI  - Macular pattern dystrophy and homonymous hemianopia in MELAS syndrome.
AB  - We report an unusual association of a pattern dystrophy of the retinal pigment
      epithelium and homonymous hemianopia in a woman diagnosed with mitochondrial
      myopathy, encephalopathy, lactic acidosis and stroke-like episodes syndrome. 

PMID- 25766437
TI  - Incidental detection of ascariasis worms on USG in a protein energy malnourished
      (PEM) child with abdominal pain.
AB  - A 10-year-old child presented with dull aching periumbilical abdominal pain for
      15 days. The child was not gaining weight despite a good appetite. Physical
      examination of the child revealed grade-I protein energy malnourishment (PEM)
      according to IAP (Indian Academic of Paediatrics) classification. The rest of the
      systemic examination was normal. Routine blood investigation revealed anaemia
      with eosinophilia. Abdominal ultrasonography did not show any abnormality with
      curvilinear transducer (3.5-5 MHz), however, linear ultrasound transducer (7.5-12
      MHz) with harmonic tissue imaging showed worms in the lumen of the small
      intestine with curling movement on real time scanning. Stool examination for the
      eggs of ascariasis was positive. The patient was treated with antihelminthic
      drugs. Dietary modification for the PEM was advised. After 3 months of treatment,
      the patient improved and stool examination for Ascaris was negative on follow-up.

PMID- 25766438
TI  - Sturge-Weber syndrome: oral and extra-oral manifestations.
AB  - Sturge-Weber syndrome is a rare, congenital, neuro-oculo-cutaneous disorder which
      is characterised extra-orally by unilateral port wine stains on the face,
      glaucoma, seizures and mental retardation, and intra-orally by ipsilateral
      gingival haemangioma which frequently affects the maxilla or mandible. In the
      present case, a 15-year-old female patient presented with a port wine stain on
      the right side of the face and glaucoma of the right eye, and intra-orally with
      gingival haemangioma on the right side of the maxilla. 

PMID- 25766439
TI  - Accessory pancreatic lobe with gastric duplication cyst: diagnostic challenges of
      a rare congenital anomaly.
AB  - Reports of combined congenital abnormalities of gastric duplication cysts and
      accessory pancreatic lobes are rarely reported. Patients with such anomalies may
      require appropriate surgical intervention tailored to the individual patient for
      complete cure. A multimodality diagnostic approach using ultrasonography, CT and
      MRI is useful for appreciation of the relevant anatomy of the congenital
      abnormality and for proper surgical planning. We present a case of a gastric
      duplication cyst with accessory pancreatic lobe and ectopic pancreatic rest in a
      5-year-old child presenting with symptoms of recurrent pancreatitis. 

PMID- 25766440
TI  - Renal pelvis rupture during pregnancy: diagnosing a confusing source of despair.
AB  - We present an impressive case of a pregnant woman presenting with severe right
      flank pains. A rare rupture of the right renal pelvis turned out to be the cause
      of her problems. Renal pelvis rupture in pregnancy is difficult to diagnose. It
      is easily confused with other more prevalent diagnoses, like hydronephrosis,
      ureteral distension, renal calculus and pyelonephritis. Ultrasonography is not
      always conclusive. Pyelography seems to be a good diagnostic tool, this case
      shows that MRI is another option. Renal pelvis rupture can be effectively treated
      with the insertion of a JJ-stent. 

PMID- 25766441
TI  - Use of congenital pouch colon for augmenting the neurogenic bladder in a child: a
      13-year follow-up.
AB  - Congenital pouch colon is an anomaly always associated with anorectal
      malformation, where the colon is replaced by or terminates into a large
      aperistaltic intestinal pouch. Vertebral anomalies leading to neurogenic bladder
      are rare associated malformations. The pouch is aperistaltic and thus a poor
      rectal substitute but this very property makes it ideal for bladder augmentation.
      We report the first case where the pouch has been used to augment a high-pressure
      neurogenic bladder. 

PMID- 25766442
TI  - Acute exacerbation of dysphagia due to foreign body impaction in an oesophageal
      stricture due to eosinophilic esophagitis.
AB  - A 43-year woman with a 4-year history of swallowing difficulty for solids
      presented with absolute dysphagia, which was only slightly relieved by
      intravenous relaxant given in the emergency department. Barium swallow showed a
      smooth polypoid filling defect in the mid-oesophagus, with a hold-up at this
      level. Gastroscopy showed a narrowed ringed oesophagus with an impacted foreign
      body. This was extracted with a basket, with relief of the dysphagia. Oesophageal
      biopsies confirmed the diagnosis of eosinophilic esophagitis. 

PMID- 25766443
TI  - Gallstone pancreatitis secondary to a pathological cystic duct stump in a setting
      of chronic pain syndrome: a diagnostic dilemma.
AB  - A 32-year-old woman presented with epigastric pain. She was a patient with
      chronic pain syndrome and had visited the emergency department several times over
      the past year. She did not drink alcohol. She had a laparoscopic cholecystectomy
      for gallstone pancreatitis 4 years ago. Her lipase was 2020 with normal
      bilirubin. MR cholangiopancreatography revealed a cystic structure resembling a
      gallbladder in the gallbladder fossa. This was in connection with the biliary
      system. The structure also contained stones. A review of the histology did
      confirm the gallbladder had been removed. She proceeded to have a laparoscopic re
      cholecystectomy and made an unremarkable recovery.

PMID- 25766444
TI  - Steroid-responsive encephalopathy: an under recognised aspect of Hashimoto's
      thyroiditis.
AB  - We present a case of a patient who was diagnosed with Hashimoto's encephalopathy
      based on the presence of subacute behavioural changes, negative work up for
      infection and immunological serology except for high serum titres of thyroid
      autoantibodies. Thyroid function tests (TFTs) and MRI of the brain were normal.
      EEG showed low amplitude, slow waves and theta waves at both frontal areas. His
      condition improved dramatically after treated with high-dose glucocorticoid.
      After 2 years of a relapsing-remitting course, a new episode occurred. There was
      an abrupt change of TFTs within 5 days: free thyroxine (fT4) from 1.52 to 1.53
      ng/mL, free triiodothyronine (fT3) from 3.25 to >30 pg/mL and thyroid-stimulating
      hormone (TSH) from 5.08 to 0.78 mIU/L. On the following day found fT4 2.58, fT3
      14.67 and TSH 0.042. The patient was diagnosed with Hashitoxicosis. High-dose
      glucocorticoid and beta-blockers were initiated. The symptoms gradually improved
      and TFTs normalised within 2 weeks. 

PMID- 25766445
TI  - Cardiac rhabdomyoma: an antenatal illustration.

PMID- 25766447
TI  - Eccrine squamous syringometaplasia of underlying syringoma associated with
      Tegafur/Gimeracil/Oteracil (TS-1).

PMID- 25766446
TI  - High correlation between genotypes and phenotypes of environmental bacteria
      Comamonas testosteroni strains.
AB  - BACKGROUND: Members of Comamonas testosteroni are environmental microorganisms
      that are usually found in polluted environment samples. They utilize steroids and
      aromatic compounds but rarely sugars, and show resistance to multiple heavy
      metals and multiple drugs. However, comprehensive genomic analysis among the C.
      testosteroni strains is lacked. RESULTS: To understand the genome bases of the
      features of C. testosteroni, we sequenced 10 strains of this species and analyzed
      them together with other related published genome sequences. The results revealed
      that: 1) the strains of C. testosteroni have genome sizes ranging from 5.1 to 6.0
      Mb and G + C contents ranging from 61.1% to 61.8%. The pan-genome contained
      10,165 gene families and the core genome contained 3,599 gene families. Heap's
      law analysis indicated that the pan-genome of C. testosteroni may be open (alpha
      = 0.639); 2) by analyzing 31 phenotypes of 11 available C. testosteroni strains,
      99.4% of the genotypes (putative genes) were found to be correlated to the
      phenotypes, indicating a high correlation between phenotypes and genotypes; 3)
      gene clusters for nitrate reduction, steroids degradation and metal and multi
      drug resistance were found and were highly conserved among all the genomes of
      this species; 4) the genome similarity of C. testosteroni may be related to the
      geographical distances. CONCLUSIONS: This work provided an overview on the
      genomes of C. testosteroni and new genome resources that would accelerate the
      further investigations of this species. Importantly, this work focused on the
      analysis of potential genetic determinants for the typical characters and found
      high correlation between the phenotypes and their corresponding genotypes.

PMID- 25766449
TI  - In memoriam: D. Alan Stubbs, 1940-2014.

PMID- 25766448
TI  - Effect of the cumin cyminum L. Intake on Weight Loss, Metabolic Profiles and
      Biomarkers of Oxidative Stress in Overweight Subjects: A Randomized Double-Blind
      Placebo-Controlled Clinical Trial.
AB  - BACKGROUND: The current study was performed to determine the effects of cumin
      cyminum L. intake on weight loss and metabolic profiles among overweight
      subjects. METHODS: This randomized double-blind placebo-controlled clinical trial
      was conducted among 78 overweight subjects (male, n = 18; female, n = 60) aged 18
      60 years old. Participants were randomly assigned into three groups to receive:
      (1) cumin cyminum L. capsule (n = 26); (2) orlistat120 capsule (n = 26) and (3)
      placebo (n = 26) three times a day for 8 weeks. Anthropometric measures and
      fasting blood samples were taken at baseline and after 8 weeks of intervention.
      RESULTS: Consumption of the Cuminum cyminum L. and orlistat120 resulted in a
      similar significant decrease in weight (-1.1 +/- 1.2 and -0.9 +/- 1.5 vs. 0.2 +/-
      1.5 kg, respectively, p = 0.002) and BMI (-0.4 +/- 0.5 and -0.4 +/- 0.6 vs. 0.1
      +/- 0.6 kg/m(2), respectively, p = 0.003) compared with placebo. In addition,
      taking Cuminum cyminum L., compared with orlistat and placebo, led to a
      significant reduction in serum insulin levels (-1.4 +/- 4.5 vs. 1.3 +/- 3.3 and
      0.3 +/- 2.2 uIU/ml, respectively, p = 0.02), HOMA-B (-5.4 +/- 18.9 vs. 5.8 +/-
      13.3 and 1.0 +/- 11.0, respectively, p = 0.02) and a significant rise in QUICKI
      (0.01 +/- 0.01 vs. -0.005 +/- 0.01 and -0.004 +/- 0.01, respectively, p = 0.02).
      CONCLUSION: Taking cumin cyminum L. for eight weeks among overweight subjects had
      the same effects of orlistat120 on weight and BMI and beneficial effects on
      insulin metabolism compared with orlistat120 and placebo.

PMID- 25766450
TI  - Arbitrary conditional discriminative functions of meaningful stimuli and enhanced
      equivalence class formation.
AB  - Equivalence class formation by college students was influenced through the prior
      acquisition of conditional discriminative functions by one of the abstract
      stimuli (C) in the to-be-formed classes. Participants in the GR-0, GR-1, and GR-5
      groups attempted to form classes under the simultaneous protocol, after mastering
      0, 1, or 5 conditional relations between C and other abstract stimuli (V, W, X,
      Y, Z) that were not included in the to-be-formed classes (ABCDE). Participants in
      the GR-many group attempted to form classes that contained four abstract stimuli
      and one meaningful picture as the C stimulus. In the GR-0, GR-1, GR-5, and GR
      many groups, classes were formed by 17, 25, 58, and 67% of participants,
      respectively. Thus, likelihood of class formation was enhanced by the prior
      formation of five C-based conditional relations (the GR-5 vs. GR-0 condition), or
      the inclusion of a meaningful stimulus as a class member (the GR-many vs. GR-0
      condition). The GR-5 and GR-many conditions produced very similar yields,
      indicating that class formation was enhanced to a similar degree by including a
      meaningful stimulus or an abstract stimulus that had become a member of five
      conditional relations prior to equivalence class formation. Finally, the low and
      high yields produced by the GR-1 and GR-5 conditions showed that the class
      enhancement effect of the GR-5 condition was due to the number of conditional
      relations established during preliminary training and not to the sheer amount of
      reinforcement provided while learning these conditional relations. Class
      enhancement produced by meaningful stimuli, then, can be attributed to their
      acquired conditional discriminative functions as well as their discriminative,
      connotative, and denotative properties. 

PMID- 25766451
TI  - Is there time discounting for risk premium?
AB  - Individuals with a higher subjective discount rate concentrate more on the
      present and delay is more significant for them. However, when a risky asset is
      delayed, not only is the outcome delayed but also the risk. In this paper, we
      suggest a new, two-stage experimental method with real monetary incentives that
      allows us to distinguish between the effect of the risk and the effect of the
      time when pricing a risky asset. We show that when individuals have greater
      preference for the present, their risk aversion for a risky asset realized in the
      future decreases. We argue that the effect of the risk for future asset is lower
      for individuals with higher time preference because they discount not only the
      outcome but also the risks. 

PMID- 25766452
TI  - Conditioned reinforcement and information theory reconsidered.
AB  - The idea that stimuli might function as conditioned reinforcers because of the
      information they convey about primary reinforcers has a long history in the study
      of learning. However, formal application of information theory to conditioned
      reinforcement has been largely abandoned in modern theorizing because of its
      failures with respect to observing behavior. In this paper we show how recent
      advances in the application of information theory to Pavlovian conditioning offer
      a novel approach to conditioned reinforcement. The critical feature of this
      approach is that calculations of information are based on reductions of
      uncertainty about expected time to primary reinforcement signaled by a
      conditioned reinforcer. Using this approach, we show that previous failures of
      information theory with observing behavior can be remedied, and that the
      resulting framework produces predictions similar to Delay Reduction Theory in
      both observing-response and concurrent-chains procedures. We suggest that the
      similarity of these predictions might offer an analytically grounded reason for
      why Delay Reduction Theory has been a successful theory of conditioned
      reinforcement. Finally, we suggest that the approach provides a formal basis for
      the assertion that conditioned reinforcement results from Pavlovian conditioning
      and may provide an integrative approach encompassing both domains. 

PMID- 25766453
TI  - Quotation. Paul Souriau on self-awareness.

PMID- 25766455
TI  - Effect of abdominal resistance exercise on abdominal subcutaneous fat of obese
      women: a randomized controlled trial using ultrasound imaging assessments.
AB  - OBJECTIVES: The aim of this study was to compare the effect of diet and an
      abdominal resistance training program to diet alone on abdominal subcutaneous fat
      thickness and waist circumference of overweight and obese women. METHODS: This
      randomized clinical trial included 40 overweight and obese women randomly divided
      into 2 groups: diet only and diet combined with 12 weeks of abdominal resistance
      training. Waist and hip circumferences and abdominal skin folds of the subjects
      were measured at the beginning and 12 weeks after the interventions. In addition,
      abdominal subcutaneous fat thickness of the subjects was measured using
      ultrasonography. Percentage body fat and lean body mass of all the subjects were
      also measured using a bioelectric impedance device. RESULTS: After 12 weeks of
      intervention, the weight of participants in both groups decreased; but the
      difference between the 2 groups was not significant (P = .45). Similarly, other
      variables including abdominal subcutaneous fat, waist circumference, hip
      circumference, body mass index, body fat percentage, and skin fold thickness were
      reduced in both groups; but there were no significant differences between the
      groups. CONCLUSIONS: This study found that abdominal resistance training besides
      diet did not reduce abdominal subcutaneous fat thickness compared to diet alone
      in overweight or obese women.

PMID- 25766456
TI  - Feedback for patients reporting adverse drug reactions; satisfaction and
      expectations.
AB  - OBJECTIVE: Due to the rising number of patient reports in pharmacovigilance, the
      manner in which feedback is provided to patients is an element to be considered.
      The objective is to explore the satisfaction of patients towards personalized and
      general feedback in response to their reported adverse drug reactions (ADRs).
      METHODS: Patients who reported an ADR to the Dutch Pharmacovigilance Centre for
      the first time in the period between October 2012 and April 2013 were included.
      Reporters received personalized feedback or a general acknowledgement letter.
      Satisfaction towards the received feedback, expressed on a 5-point Likert scale
      (1 very good to 5 very poor), was studied using a web-based questionnaire. Data
      were analyzed using Pearson Chi-square test and linear regression analysis.
      Statistical significance was based on p < 0.05. RESULTS: A total of 471 patient
      reporters were contacted with a total response of 52.5%. Respondents of both
      groups were satisfied with the received feedback, average score 2 (good).
      Respondents of the personalized feedback-group were however more satisfied score
      2.0 versus 2.5 (p < 0.001) and considered the feedback more clear and useful
      compared with respondents of the acknowledgement letter-group, respectively score
      1.6 versus 1.7 (p = 0.01) and score 2.1 versus 2.5 (p < 0.001). CONCLUSION:
      Patients reporting ADRs are satisfied with feedback received from the
      pharmacovigilance centre, whether this is a personalized feedback or a general
      acknowledgment letter. They find it clear, useful and it meets their expectation.
      Although differences were found between the two types of feedback, these
      differences did not indicate dissatisfaction towards the received feedback.

PMID- 25766457
TI  - The impact of the Bellagio Report on healthy agriculture, healthy nutrition,
      healthy people: scientific and policy aspects and the International Network of
      Centers for Genetics, Nutrition and Fitness for Health.
AB  - The Bellagio Report on Healthy Agriculture, Healthy Nutrition, Healthy People was
      the result of a meeting held at the Rockefeller Foundation Bellagio Center in the
      fall of 2012. The meeting was science based but policy oriented. The Bellagio
      Report concluded that: (1) sugar consumption, especially in the form of high
      energy fructose in soft drinks, poses a major and insidious health threat,
      particularly for children; (2) current diets in most populations, albeit with
      regional differences, are deficient in omega-3 fatty acids but too high in omega
      6 fatty acid intake, and (3) not all calories are the same since calories from
      different sources (i.e. glucose or fructose or omega-6 or omega-3 fatty acids)
      have different metabolic and neurohormonal effects. This paper summarizes the
      scientific progress and policy actions that have occurred in these three areas.
      Genetic variation in populations and gene-nutrient interactions are fundamental
      concepts that need to be taken into consideration in growth and development and
      in the prevention and management of chronic noncommunicable diseases since there
      is enormous variation in both the frequency of genetic variants and dietary
      composition worldwide. Furthermore, this paper updates the Bellagio Report in
      terms of the scientific and policy aspects, both of which have expanded over the
      past 2 years, and describes the progress made in establishing an International
      Network of Centers for Genetics, Nutrition and Fitness for Health.

PMID- 25766458
TI  - Automated point-of-care testing for ABO agglutination test: proof of concept and
      validation.
AB  - BACKGROUND AND OBJECTIVES: ABO-incompatible red blood cell transfusions still
      represent an important hazard in transfusion medicine. Therefore, some countries
      have introduced a systematic bedside ABO agglutination test checking that the
      right blood is given to the right patient. However, this strategy requires an
      extremely time-consuming learning programme and relies on a subjective
      interpretation of ABO test cards agglutination. We developed a prototype of a
      fully automated device performing the bedside agglutination test that could be
      completed by reading of a barcoded wristband. This POCT checks the ABO
      compatibility between the patient and the blood bag. MATERIALS AND METHODS: Proof
      of concept and analytical validation of the prototype has been completed on 451
      blood samples: 238 donor packed red blood cells, 137 consecutive unselected
      patients for whom a blood group determination had been ordered and on 76 patient
      samples selected with pathology that could possibly interfere with or impair
      performances of the assay. RESULTS: We observed 100% concordance for ABO blood
      groups between the POCT and the laboratory instrument. CONCLUSION: These
      preliminary results demonstrate the feasibility of ABO determination with a
      simple POCT device eliminating manipulation and subjective interpretation
      responsible for transfusion errors. This device should be linked to the blood
      bank system allowing all cross-check of the results.

PMID- 25766459
TI  - Tsutomu Katsuki (1946-2014).

PMID- 25766460
TI  - Response to "Setbacks of transoral temporomandibular joint ankylotic mass
      excision".

PMID- 25766461
TI  - Assessment of sagittal split ramus osteotomy rigid internal fixation techniques
      using a finite element method.
AB  - In this study, finite element analysis (FEA) was used to evaluate nine rigid
      internal fixation techniques for sagittal split ramus osteotomy. To achieve this,
      a computed tomography (CT) scan of a healthy patient was obtained and used to
      generate the geometry of a half-mandible. The geometries of bicortical screws,
      miniplates, and monocortical screws were designed and combined with the mandible
      in nine models simulating various techniques. Four models used bicortical screws
      in various arrangements and four used miniplates of various designs. One model
      represented a hybrid technique. A load of 500 N was applied to the posterior
      teeth and FEA was applied. The most stable techniques were the hybrid technique
      and a single straight miniplate, presenting the least displacement among all
      models. Bicortical screws, while presenting reasonable stability, showed high
      strain areas near the anterior ramus ridge, superoposterior to the screws,
      implying a risk of bone fracture in this area. On the other hand, the T-shaped
      and double Y-shaped miniplates were associated with high von Mises stresses that
      would impair their rigidity, especially where angles appeared in their designs.
      We recommend the use of a single straight miniplate because it provides
      sufficient stable fixation with minimal risks or disadvantages.

PMID- 25766462
TI  - Neuromyelitis optica with cutaneous findings: case report and review of the
      literature.
AB  - Neuromyelitis optica (NMO) is an autoimmune, relapsing central nervous system
      demyelinating disease. There is a known association between NMO and autoimmune
      disease. However, cutaneous findings in these cases and in the setting of
      isolated NMO have rarely been described. We report the case of a 60-year-old
      Chinese female who presented with nonspecific cutaneous findings and acute onset
      paraplegia and was subsequently found to be seropositive for aquaporin-4 (NMO
      IgG) antibodies, consistent with a diagnosis of NMO spectrum disorder. Serologic
      testing prompted by history and cutaneous stigmata revealed additional humoral
      derangements, together suggestive of an overlap syndrome with features of
      amyopathic dermatomyositis, rheumatoid arthritis and lupus erythematosus. We
      review the existing literature on the cutaneous manifestations of this entity.
      Awareness of the cutaneous signs and heralding symptoms of this devastating
      neurologic syndrome by dermatologists will ensure prompt diagnosis and initiation
      of treatment that can minimize neurologic sequelae.

PMID- 25766464
TI  - Controlling multidrug-resistant Gram-negative bacilli in your hospital: a
      transformational journey.
AB  - During the past two decades, the world has experienced a proliferation of
      multidrug-resistant Gram-negative organisms. This paper is an account of the
      author's personal experience of implementing a bundle of interventions aimed at
      controlling carbapenem-resistant Acinetobacter baumannii, and of the cultural
      transformation that was required for effective control. 

PMID- 25766465
TI  - Association between hyperglycemia and retinopathy of prematurity: a systemic
      review and meta-analysis.
AB  - As the role of hyperglycemia in the development of retinopathy of prematurity
      (ROP) has not been well established, a meta-analysis of the association between
      hyperglycemia and ROP was conducted. Studies were identified through literature
      search in MEDLINE and EMBASE up to June 20, 2014 with keywords related to
      "hyperglycaemia" and "ROP". Nine eligible studies involving 1939 neonates with
      509 cases of ROP were included. Unadjusted analyses showed that hyperglycemia was
      significantly associated with ROP (Odds ratio [OR] = 4.16, P<0.0001). Comparing
      with the control, subjects in the ROP group had a significantly longer duration
      of hyperglycemia (Standardized mean difference [SMD] = 1.21, P< 0.0001), and
      higher mean glucose level. (SMD = 0.88, P = 0.0004) However, when combining the
      adjusted OR (after adjustment for birth weight, gestational age and other
      factors) provided from individual studies, only borderline significant
      association were observed on duration of hyperglycemia with ROP (adjusted OR
      1.08, P = 0.03); and no significant association on mean glucose level with ROP
      (adjusted OR = 1.08, P = 0.15). Hence, hyperglycemia cannot be definitely
      considered as a risk factor for ROP, and further studies should adjust for
      potential confounding factors to clarify this association. 

PMID- 25766466
TI  - The risk of manipulation under anesthesia due to unsatisfactory knee flexion
      after fast-track total knee arthroplasty.
AB  - BACKGROUND: Fast-track TKA has significantly shortened the time available for
      physiotherapists to optimize knee ROM before discharge. Safety aspects concerning
      knee stiffness and the need for manipulation in a fast-track setting need to be
      illuminated. The study aims were to analyze if fast-track TKA can be considered
      safe considering rates of knee manipulation and if there is an association
      between knee ROM at time of discharge and the need for later manipulation.
      METHODS: Primary TKAs operated in 2011 at our institution were eligible for
      inclusion. The study group consisted of 359 TKAs. RESULTS: Manipulation of the
      knee was performed in 21 of 359 TKAs (5.8%). Seventy-one percent were discharged
      with a flexion >=70 degrees  combined with an extension deficit of <=10 degrees .
      The occurrence of MUA for these patients was 4.3%. The prevalence of knee
      manipulation showed a statistically significant association with the achieved
      knee flexion at discharge (p=0.02). Median length of stay was two days.
      CONCLUSION: Compared with literature findings fast-track TKA surgery may be
      considered safe based on the acceptable rate of knee manipulations after TKA
      (5.8%). We suggest ROM of >=70 degrees  flexion combined with an extension
      deficit of <=10 degrees  as an "optimal-zone" for ROM at discharge. The reason
      for this is the low occurrence of MUA (4.3%) in relation to the large amount of
      TKAs it represents (71%). The indication for MUA is multifactorial and ROM at
      discharge serves only as an indicator of later MUA risk.

PMID- 25766469
TI  - Comparison of chemical composition of enamel and dentine in human, bovine,
      porcine and ovine teeth.
AB  - OBJECTIVE: The aim of this paper was to compare the chemical composition of human
      teeth with other mammal species that are likely candidates for replacing them in
      studies that test dental material. DESIGN: Dentine and enamel fragments extracted
      from 400 sound human, bovine, porcine and ovine - 100 teeth per species -
      incisors and molars were mechanically ground up to a final particle size of less
      than 100 MUm. C/N analysis, thermogravimetric analysis coupled to mass
      spectrometry (TG-MS), and wavelength dispersive X-ray fluorescence (WDXRF) were
      used to analyse the samples' composition. RESULTS: Elemental analysis showed more
      organic carbon and nitrogen in dentine than in enamel. Human enamel was the most
      highly mineralised, with C and N values close to hydroxyapatite. Bovine dentine
      and enamel were the most similar to human. TG-MS: in all species, enamel
      contained less carbon and organic matter than dentine. Thermal decomposition of
      human enamel showed great similarity to synthetic hydroxyapatite, and large
      differences from bovine, ovine and porcine enamel. Thermal decomposition showed
      the greatest similarity between human and bovine dentine. WDXRF: Dentine
      contained larger quantities of Mg, S, Sr and Zn than enamel. Enamel contained
      larger quantities of P, Ca, Cl, Cu, K and Ca/P ratio than dentine. Human enamel
      and dentine contained a higher Ca/P ratio, larger quantities of Cl and Cu and
      lower quantities of Mg, S, Zn than the animal species. CONCLUSIONS: Elemental
      analysis, TG-MS and WDXRF have shown that human and bovine enamel and dentine
      show the greatest similarity among the species analysed.

PMID- 25766468
TI  - Radiotherapy effect on nano-mechanical properties and chemical composition of
      enamel and dentine.
AB  - OBJECTIVE: To understand radiotherapy-induced dental lesions characterized by
      enamel loss or delamination near the dentine-enamel junction (DEJ), this study
      evaluated enamel and dentine nano-mechanical properties and chemical composition
      before and after simulated oral cancer radiotherapy. DESIGN: Sections from seven
      non-carious third molars were exposed to 2 Gy fractions, 5 days/week for 7 weeks
      for a total of 70 Gy. Nanoindentation was used to evaluate Young's modulus, while
      Raman microspectroscopy was used to measure protein/mineral ratios,
      carbonate/phosphate ratios, and phosphate peak width. All measures were completed
      prior to and following radiation at the same four buccal and lingual sites 500
      and 30 MUm from the DEJ in enamel and dentine (E-500, E-30, D-30 and D-500).
      RESULTS: The elastic modulus of enamel and dentine was significantly increased (P
      <= 0.05) following radiation. Based on Raman spectroscopic analysis, there was a
      significant decrease in the protein to mineral ratio (2931/430 cm(-1)) following
      radiation at all sites tested except at D-500, while the carbonate to phosphate
      ratio (1070/960 cm(-1)) increased at E-30 and decreased at D-500. Finally,
      phosphate peak width as measured by FWHM at 960 cm(-1) significantly decreased at
      both D-30 and D-500 following radiation. CONCLUSIONS: Simulated radiotherapy
      produced an increase in the stiffness of enamel and dentine near the DEJ.
      Increased stiffness is speculated to be the result of the radiation-induced
      decrease in the protein content, with the percent reduction much greater in the
      enamel sites. Such changes in mechanical properties and chemical composition
      could potentially contribute to DEJ biomechanical failure leading to enamel
      delamination that occurs post-radiotherapy. However, other analyses are required
      for a better understanding of radiotherapy-induced effects on tooth structure to
      improve preventive and restorative treatments for oral cancer patients.

PMID- 25766470
TI  - Effect of alendronate sodium on tooth movement in ovariectomized rats.
AB  - OBJECTIVES: The aim of the present study was to evaluate the effect of two
      different dosages of alendronate on induced orthodontic movement in an
      experimental model involving rats with osteoporosis following ovariectomy.
      DESIGN: Female Wistar rats (Rattus norvegicus) eight weeks of age were divided
      into four groups (n=12/group): ovariectomized (OVX group); ovariectomized and
      treated with alendronate sodium at 1mg/kg (Group OVX+ALN1); ovariectomized and
      treated with alendronate sodium at 2mg/kg (Group OVX+ALN2); and sham operated
      (control). Three months after ovariectomy, the maxillary right first molar was
      submitted to movement for five and seven days. After the death of the animals,
      the maxilla were removed and processed for microscopic evaluation. The maxillary
      left first molar (without movement) was used for comparison purposes in all
      groups. The samples were processed for the quantification of alveolar bone and
      tooth movement. RESULTS: Intragroup comparisons showed significant movement after
      five and seven days (p<0.05) for all groups. Comparison among groups revealed
      greater tooth movement in the OVX group (p<0.05), on day 7. CONCLUSIONS: Both
      alendronate sodium doses similarly decreased tooth movement in ovariectomized
      rats (p>0.05). Movement in ovariectomized+alendronate groups were also smaller
      than non-ovariectomized rats, however without statistical difference.

PMID- 25766467
TI  - Perinatally administered losartan augments renal ACE2 expression but not cardiac
      or renal Mas receptor in spontaneously hypertensive rats.
AB  - Since the identification of the alternative angiotensin converting enzyme
      (ACE)2/Ang-(1-7)/Mas receptor axis, renin-angiotensin system (RAS) is a new
      complex target for a pharmacological intervention. We investigated the expression
      of RAS components in the heart and kidney during the development of hypertension
      and its perinatal treatment with losartan in young spontaneously hypertensive
      rats (SHR). Expressions of RAS genes were studied by the RT-PCR in the left
      ventricle and kidney of rats: normotensive Wistar, untreated SHR, SHR treated
      with losartan since perinatal period until week 9 of age (20 mg/kg/day) and SHR
      treated with losartan only until week 4 of age and discontinued until week 9. In
      the hypertrophied left ventricle of SHR, cardiac expressions of Ace and Mas were
      decreased while those of AT1 receptor (Agtr1a) and Ace2 were unchanged.
      Continuous losartan administration reduced LV weight (0.43 +/- 0.02; P < 0.05
      versus SHR) but did not influence altered cardiac RAS expression. Increased blood
      pressure in SHR (149 +/- 2 in SHR versus 109 +/- 2 mmHg in Wistar; P < 0.05) was
      associated with a lower renal expressions of renin, Agtr1a and Mas and with an
      increase in ACE2. Continuous losartan administration lowered blood pressure to
      control levels (105 +/- 3 mmHg; P < 0.05 versus SHR), however, only renal renin
      and ACE2 were significantly up-regulated (for both P < 0.05 versus SHR).
      Conclusively, prevention of hypertension and LV hypertrophy development by
      losartan was unrelated to cardiac or renal expression of Mas. Increased renal
      Ace2, and its further increase by losartan suggests the influence of locally
      generated Ang-(1-7) in organ response to the developing hypertension in SHRs.

PMID- 25766471
TI  - The frequency of Helicobacter pylori in dental plaque is possibly underestimated.
AB  - OBJECTIVE: The commonest bacteria, causing infection across the world is
      Helicobacter pylori, which colonizes the human stomach. This bacteria has also
      been detected in some extra-gastric ecological niches such as the oral cavity and
      water. However, the results of H. pylori detection in extra-gastric ecological
      niche are controversial. The improvement of the sensitivity and the specificity
      of the detection methods appear to be some of the main bottleneck issues in
      providing compelling evidence. The aim of this study was to detect the presence
      of this organism in dental plaque samples using an analytically sensitive and
      specific Polymerase Chain Reaction (PCR) as well as a new nucleic acid detection
      method termed the Loop-mediated Isothermal Amplification (LAMP). DESIGN: In a
      descriptive cross-sectional study 45 participants enrolled and dental plaque
      samples were collected from at least two teeth surfaces (one anterior and one
      posterior tooth) using a sterile periodontal curette. The DNA content was
      extracted from the samples and the presence of H. pylori was determined by PCR
      and LAMP reactions. RESULTS: The frequency of detection of H. pylori in the
      dental plaque samples were 44% (20/45), 66.67% (30/45) and 77.78% (35/45) using
      PCR, LAMP and positivity for both tests, respectively. CONCLUSION: The high
      frequency of H. pylori was detected in the dental plaque samples of the
      participants, which concurs with the high prevalence of this bacteria in the
      population. This is one of the highest reported rates around the world. The
      results reveal that dental plaque can be one of the main causes of re-infection
      and also be the cause of oral-oral transmission.

PMID- 25766472
TI  - Oral administration of 5-hydroxytryptophan aggravated periodontitis-induced
      alveolar bone loss in rats.
AB  - OBJECTIVE: 5-Hydroxytryptophan (5-HTP) is the precursor of serotonin and 5-HTP
      has been widely used as a dietary supplement to raise serotonin level. Serotonin
      has recently been discovered to be a novel and important player in bone
      metabolism. As peripheral serotonin negatively regulates bone, the regular take
      of 5-HTP may affect the alveolar bone metabolism and therefore influence the
      alveolar bone loss induced by periodontitis. The aim of this study was to
      investigate the effect of 5-HTP on alveolar bone destruction in periodontitis.
      DESIGN: Male Sprague-Dawley rats were randomly divided into the following four
      groups: (1) the control group (without ligature); (2) the 5-HTP group (5-HTP at
      25 mg/kg/day without ligature); (3) the L group (ligature+saline placebo); and
      (4) the L+5-HTP group (ligature+5-HTP at 25 mg/kg/day). Serum serotonin levels
      were determined by ELISA. The alveolar bones were evaluated with micro-computed
      tomography and histology. Tartrate-resistant acid phosphatase staining was used
      to assess osteoclastogenesis. The receptor activator of NF-kB ligand (RANKL) and
      osteoprotegerin (OPG) expression in the periodontium as well as the interleukin-6
      positive osteocytes were analysed immunohistochemically. RESULTS: 5-HTP
      significantly increased serum serotonin levels. In rats with experimental
      periodontitis, 5-HTP increased alveolar bone resorption and worsened the micro
      structural destruction of the alveolar bone. 5-HTP also stimulated
      osteoclastogenesis and increased RANKL/OPG ratio and the number of IL-6 positive
      osteocytes. However, 5-HTP treatment alone did not cause alveolar bone loss in
      healthy rats. CONCLUSION: The present study showed that 5-HTP aggravated alveolar
      bone loss, deteriorated alveolar bone micro-structure in the presence of
      periodontitis, which suggests 5-HTP administration may increase the severity of
      periodontitis.

PMID- 25766474
TI  - Scaled Quantum Mechanical scale factors for vibrational calculations using
      alternate polarized and augmented basis sets with the B3LYP density functional
      calculation model.
AB  - The Scaled Quantum Mechanical (SQM) method of scaling calculated force constants
      to predict theoretically calculated vibrational frequencies is expanded to
      include a broad array of polarized and augmented basis sets based on the split
      valence 6-31G and 6-311G basis sets with the B3LYP density functional. Pulay's
      original choice of a single polarized 6-31G(d) basis coupled with a B3LYP
      functional remains the most computationally economical choice for scaled
      frequency calculations. But it can be improved upon with additional polarization
      functions and added diffuse functions for complex molecular systems. The new
      scale factors for the B3LYP density functional and the 6-31G, 6-31G(d), 6
      31G(d,p), 6-31G+(d,p), 6-31G++(d,p), 6-311G, 6-311G(d), 6-311G(d,p), 6
      311G+(d,p), 6-311G++(d,p), 6-311G(2d,p), 6-311G++(2d,p), 6-311G++(df,p) basis
      sets are shown. The double d polarized models did not perform as well and the
      source of the decreased accuracy was investigated. An alternate system of
      generating internal coordinates that uses the out-of plane wagging coordinate
      whenever it is possible; makes vibrational assignments via potential energy
      distributions more meaningful. Automated software to produce SQM scaled
      vibrational calculations from different molecular orbital packages is presented. 

PMID- 25766473
TI  - Notch1-Dll4 signalling and mechanical force regulate leader cell formation during
      collective cell migration.
AB  - At the onset of collective cell migration, a subset of cells within an initially
      homogenous population acquires a distinct 'leader' phenotype with characteristic
      morphology and motility. However, the factors driving the leader cell formation
      as well as the mechanisms regulating leader cell density during the migration
      process remain to be determined. Here we use single-cell gene expression analysis
      and computational modelling to show that the leader cell identity is dynamically
      regulated by Dll4 signalling through both Notch1 and cellular stress in a
      migrating epithelium. Time-lapse microscopy reveals that Dll4 is induced in
      leader cells after the creation of the cell-free region and leader cells are
      regulated via Notch1-Dll4 lateral inhibition. Furthermore, mechanical stress
      inhibits Dll4 expression and leader cell formation in the monolayer.
      Collectively, our findings suggest that a reduction of mechanical force near the
      boundary promotes Notch1-Dll4 signalling to dynamically regulate the density of
      leader cells during collective cell migration. 

PMID- 25766475
TI  - A Cu2+-selective fluorescent chemosensor based on BODIPY with two pyridine
      ligands and logic gate.
AB  - A novel near-infrared fluorescent chemosensor based on BODIPY (Py-1) has been
      synthesized and characterized. Py-1 displays high selectivity and sensitivity for
      sensing Cu(2+) over other metal ions in acetonitrile. Upon addition of Cu(2+)
      ions, the maximum absorption band of Py-1 in CH3CN displays a red shift from 603
      to 608 nm, which results in a visual color change from pink to blue. When Py-1 is
      excited at 600 nm in the presence of Cu(2+), the fluorescent emission intensity
      of Py-1 at 617 nm is quenched over 86%. Notably, the complex of Py-1-Cu(2+) can
      be restored with the introduction of EDTA or S(2-). Consequently, an IMPLICATION
      logic gate at molecular level operating in fluorescence mode with Cu(2+) and S(2
      ) as chemical inputs can be constructed. Finally, based on the reversible and
      reproducible system, a nanoscale sequential memory unit displaying "Writing
      Reading-Erasing-Reading" functions can be integrated.

PMID- 25766476
TI  - Structural, optical, thermal and mechanical properties of Urea tartaric acid
      single crystals.
AB  - Urea tartaric acid (UT) an organic nonlinear optical (NLO) material was
      synthesized from aqueous solution and the crystals were grown by the slow
      evaporation technique. The single crystal X-ray diffraction (XRD) analysis
      revealed that the UT crystal belongs to the orthorhombic system. The functional
      groups of UT have been identified by the Fourier transform infrared spectral
      studies. The optical transparent window in the visible and near the IR regions
      was investigated. The transmittance of UT has been used to calculate the
      refractive index (n) as a function of the wavelength. The nonlinear optical
      property of the grown crystal has been confirmed by the Kurtz powder second
      harmonic generation test. The birefringence of the crystal was determined using a
      tungsten halogen lamp source. The laser induced surface damage threshold for the
      grown crystal was measured using the Nd:YAG laser. The anisotropic in mechanical
      property of the grown crystals was studied using Vicker's microhardness tester at
      different planes. The etch pit density of UT crystals was investigated. The
      thermal behavior of UT was investigated using the TG-DTA and DSC studies.

PMID- 25766477
TI  - Highly efficient donor-acceptor hydrazone dyes-inorganic Si/TiO2 hybrid solar
      cells.
AB  - We have synthesized the two donor-bridge-acceptor organic dyes (hydrazone dye 1
      (HD1) and hydrazone dye 2 (HD2)) with the aim to enhance intra-molecular charge
      transfer then characterized by FTIR and NMR. The ground state geometries have
      been optimized at three different levels of theories, i.e., B3LYP/6-31G, B3LYP/6
      31G and Hartee-Fock HF/6-31G. The absorption spectra and oscillator strengths in
      different solvents have been computed and compared with the experimental data.
      The vibrational spectral assignments have been performed on the recorded FTIR
      spectra based on the theoretical predicted wavenumbers at three different levels
      of theories. The effect of different solvents (CHCl3, CH3CN and C2H5OH) has been
      studied on the absorption wavelengths. Furthermore, we have computed the
      ionization potentials, electron affinities and reorganization energies of studied
      compounds and shed light on the charge transport properties. The hetero-junction
      solar cell devices were fabricated by organic-inorganic hetero-junction
      (Si/TiO2/dye) then the efficiency has been measured by applying the incident
      power 30, 50 and 70 mW/cm(2). The maximum efficiency 3.12% has been observed for
      HD1.

PMID- 25766478
TI  - Structural, optical and electrical properties of Zr-doped In2O3 thin films.
AB  - Undoped and zirconium doped indium oxide (ZrIO) thin films were deposited on
      glass substrate at a substrate temperature of 450 degrees C by spray pyrolysis
      method. The effect of zirconium (Zr) dopant concentration (0-11 at.%) on the
      structural, morphological, optical and electrical properties of n-type ZrIO films
      were studied. X-ray diffraction (XRD) results confirmed the polycrystalline
      nature of the ZrIO thin film with cubic structure. The grain size was decreased
      from 25 to 15.75 nm with Zr doping. The scanning electron microscopy (SEM) showed
      that the surface morphology of the films were changed with Zr doping. The surface
      roughness of the films was investigated by atomic force microscopy (AFM) and was
      found to be increased with the increasing of Zr doping percentage. A blue shift
      of the optical band gap was observed. The optical band was gap decreased from
      3.50 to 3.0eV with increase in Zr concentrations. Room temperature
      photoluminescence (PL) measurement of the deposited films indicated the
      incorporation of Zr in In2O3 lattice. The film had low resistivity of 6.4 * 10(
      4)Omegacm and higher carrier concentration of 2.5 * 10(20) was obtained at a
      doping ratio of 7 at.%.

PMID- 25766479
TI  - Chemometrics-assisted spectrophotometric method for simultaneous determination of
      Pb2+ and Cu2+ ions in different foodstuffs, soil and water samples using 2
      benzylspiro [isoindoline-1,5'-oxazolidine]-2',3,4'-trione using continuous
      wavelet transformation and partial least squares - calculation of pKf of
      complexes with rank annihilation factor analysis.
AB  - A new multi-component analysis method based on zero-crossing point-continuous
      wavelet transformation (CWT) was developed for simultaneous spectrophotometric
      determination of Cu(2+) and Pb(2+) ions based on the complex formation with 2
      benzyl espiro[isoindoline-1,5 oxasolidine]-2,3,4 trione (BSIIOT). The absorption
      spectra were evaluated with respect to synthetic ligand concentration, time of
      complexation and pH. Therefore according the absorbance values, 0.015 mmol L(-1)
      BSIIOT, 10 min after mixing and pH 8.0 were used as optimum values. The complex
      formation between BSIIOT ligand and the cations Cu(2+) and Pb(2+) by application
      of rank annihilation factor analysis (RAFA) were investigated. Daubechies-4
      (db4), discrete Meyer (dmey), Morlet (morl) and Symlet-8 (sym8) continuous
      wavelet transforms for signal treatments were found to be suitable among the
      wavelet families. The applicability of new synthetic ligand and selected mother
      wavelets were used for the simultaneous determination of strongly overlapped
      spectra of species without using any pre-chemical treatment. Therefore, CWT
      signals together with zero crossing technique were directly applied to the
      overlapping absorption spectra of Cu(2+) and Pb(2+). The calibration graphs for
      estimation of Pb(2+) and Cu (2+)were obtained by measuring the CWT amplitudes at
      zero crossing points for Cu(2+) and Pb(2+) at the wavelet domain, respectively.
      The proposed method was validated by simultaneous determination of Cu(2+) and
      Pb(2+) ions in red beans, walnut, rice, tea and soil samples. The obtained
      results of samples with proposed method have been compared with those predicted
      by partial least squares (PLS) and flame atomic absorption spectrophotometry
      (FAAS).

PMID- 25766480
TI  - Antifouling coatings for dental implants: Polyethylene glycol-like coatings on
      titanium by plasma polymerization.
AB  - Titanium dental implants are commonly used for the replacement of lost teeth, but
      they present a considerable number of failures due to the infection on
      surrounding tissues. The aim of this paper is the development of a polyethylene
      glycol-like (PEG-like) coating on the titanium surface by plasma polymerization
      to obtain a novel improved surface with suitable low bacterial adhesion and
      adequate cell response. Surface analysis data of these coatings are presented, in
      particular, water contact angle, surface roughness, and film chemistry,
      demonstrating the presence of a PEG-like coating. Streptococcus sanguinis and
      Lactobacillus salivarius bacterial adhesion assays showed a decreased adhesion on
      the plasma polymerized samples, while cell adhesion of fibroblasts and
      osteoblasts on the treated surfaces was similar to control surfaces. Thus, the
      PEG-like antifouling coating obtained by plasma polymerization on Ti confers this
      biomaterial's highly suitable properties for dental applications, as they reduce
      the possibility of infection while allowing the tissue integration around the
      implant. 

PMID- 25766481
TI  - Identification of Campylobacter jejuni and determination of point mutations
      associated with macrolide resistance using a multiplex TaqMan MGB real-time PCR.
AB  - AIMS: The aim of the study was to develop a multiplex real-time PCR method to
      identify Campylobacter jejuni containing mutations commonly associated with
      macrolide resistance. METHODS AND RESULTS: A multiplex fluorescence real-time PCR
      assay was developed based on TaqMan minor groove binder (MGB) probes. The VS1-MGB
      probe was designed based on the VS1 gene and was used to identify Camp. jejuni.
      The 23S rDNA-MGB probe was designed to distinguish macrolide resistance mutations
      in 23S rDNA, while 57D-MGB and 74D-MGB were designed to detect resistance
      mutations in ribosomal protein L4. The specificity and accuracy of our method
      were identical to the conventional biochemical tests, mapA PCR, minimum
      inhibitory concentration (MIC) determination and DNA sequencing. The linear
      detection limit of the method was 0.03 ng genomic DNA and three colony formation
      unit (CFU) per reaction. In 6 of 18 cases, the nature of Erythromycin resistance
      could be correctly determined from natural isolates; absence of the tested
      mutations was demonstrated in the remaining four resistant isolates. CONCLUSIONS:
      A multiplex TaqMan MGB real-time PCR assay with high specificity and accuracy was
      developed to simultaneously identify Camp. jejuni and detect the gene mutations
      associated with macrolide resistance. SIGNIFICANCE AND IMPACT OF THE STUDY: This
      multiplex method can potentially simplify the identification of Camp. jejuni and
      determine macrolide resistance due to mutations in 23S rDNA or ribosomal protein
      L4. This method has a potential for application in different research areas and
      molecular surveillance.

PMID- 25766483
TI  - Integrating Different Aspects of Resting Brain Activity: A Review of
      Electroencephalographic Signatures in Resting State Networks Derived from
      Functional Magnetic Resonance Imaging.
AB  - Electroencephalography (EEG) is an established measure in the field of brain
      resting state with a range of quantitative methods (qEEG) that yield unique
      information about neuronal activation and synchronization. Meanwhile, in the last
      decade, functional magnetic resonance imaging (fMRI) studies have revealed the
      existence of more than a dozen resting state networks (RSNs), and combined qEEG
      and fMRI have allowed us to gain understanding about the relationship of qEEG and
      fMRI-RSNs. However, the overall picture is less clear because there is no a
      priori hypothesis about which EEG features correspond well to fMRI-RSNs. We
      reviewed the associations of several types of qEEG features to four RSNs
      considered as neurocognitive systems central for higher brain processes: the
      default mode network, dorsal and ventral frontoparietal networks, and the
      salience network. We could identify 12 papers correlating qEEG and RSNs in adult
      human subjects and employing a simultaneous design under a no-task resting state
      condition. A systematic overview investigates which qEEG features replicably
      relate to the chosen RSNs. This review article leads to the conclusion that
      spatially delimited theta and whole/local alpha may be the most promising
      measures, but the time domain methods add important additional information. (c)
      2015 S. Karger AG, Basel.

PMID- 25766482
TI  - CD14 expression is increased on monocytes in patients with anti-neutrophil
      cytoplasm antibody (ANCA)-associated vasculitis and correlates with the
      expression of ANCA autoantigens.
AB  - Monocyte subsets with differing functional properties have been defined by their
      expression of CD14 and CD16. We investigated these subsets in anti-neutrophil
      cytoplasm antibody (ANCA)-associated vasculitis (AAV) and determined their
      surface expression of ANCA autoantigens. Flow cytometry was performed on blood
      from 14 patients with active AAV, 46 patients with AAV in remission and 21
      controls. The proportion of classical (CD14(high) CD16(neg/low)), intermediate
      (CD14(high) CD16(high)) and non-classical (CD14(low) CD16(high)) monocytes and
      surface expression levels of CD14 and CD16 were determined, as well as surface
      expression of proteinase 3 (PR3) and myeloperoxidase (MPO) on monocyte subsets.
      There was no change in the proportion of monocytes in each subset in patients
      with AAV compared with healthy controls. The expression of CD14 on monocytes from
      patients with active AAV was increased, compared with patients in remission and
      healthy controls (P < 0.01). Patients with PR3-ANCA disease in remission also had
      increased monocyte expression of CD14 compared with controls (P < 0.01); however,
      levels in patients with MPO-ANCA disease in remission were lower than active MPO
      ANCA patients, and not significantly different from controls. There was a
      correlation between CD14 and both PR3 and MPO expression on classical monocytes
      in AAV patients (r = 0.79, P < 0.0001 and r = 0.42, P < 0.005, respectively). In
      conclusion, there was an increase in monocyte CD14 expression in active AAV and
      PR3-ANCA disease in remission. The correlation of CD14 expression with ANCA
      autoantigen expression in AAV may reflect cell activation, and warrants further
      investigation into the potential for increased CD14 expression to trigger disease
      induction or relapse.

PMID- 25766484
TI  - Effect of Patient Demographic Characteristics and Radiation Timing on PSA
      Reduction in Patients Treated With Definitive Radiation Therapy for Prostate
      Cancer.
AB  - INTRODUCTION: The purpose of this study was to assess how demographic
      characteristics and temporal factors including time to treatment (TTT) and
      elapsed time of treatment (ETT) affect prostate-specific antigen (PSA) levels
      during and after radiation treatment for low- and intermediate-risk prostate
      cancer. PATIENTS AND METHODS: A retrospective review of 1584 patients was
      conducted on patients diagnosed with prostate cancer between 2005 and 2013, from
      which 147 patients were found to have completed definitive external beam
      radiation therapy (EBRT) monotherapy. Demographic data, TTT (days between
      diagnosis and EBRT start date), ETT (days between EBRT start and stop date), and
      Gleason score were collected on these patients and analysis of variance was
      performed to analyze the relationship of these factors with PSA changes. PSA
      changes were calculated during treatment as the difference between pre- and
      posttreatment PSA levels and after treatment as 3-year and overall PSA
      velocities. RESULTS: Patients who spoke Haitian Creole (P = .039) and those with
      a longer ETT (P = .029) had significantly greater PSA decline during treatment,
      primarily as a result of higher pretreatment PSA levels. Patients with Gleason
      score 4+3 disease had significantly greater 3-year (P = .033) and overall (P =
      .019) PSA velocities. Race and/or ethnicity, insurance type, marital status, and
      age were not associated with any PSA variable. CONCLUSION: Disparities in
      prostate cancer are not reflected in PSA dynamics during or after radiation
      treatment, but are evident in PSA level at presentation. Timeliness of treatment
      was not found to affect true PSA change due to EBRT in low- and intermediate-risk
      prostate cancer patients.

PMID- 25766485
TI  - Hydroxylamine-O-sulfonic acid as an efficient coreactant for luminol
      chemiluminescence for selective and sensitive detection.
AB  - Hydroxylamine-O-sulfonic acid, a versatile reagent for organic synthesis, has
      been explored as an effective coreactant for luminol chemiluminescence. Co(2+)
      can dramatically enhance the chemiluminescence of this system. The sensitive
      detection of Co(2+), luminol and HOSA, including highly selective Co(2+)
      detection, is achieved. 

PMID- 25766486
TI  - Superhydrophobic nanocoatings: from materials to fabrications and to
      applications.
AB  - Superhydrophobic nanocoatings, a combination of nanotechnology and
      superhydrophobic surfaces, have received extraordinary attention recently,
      focusing both on novel preparation strategies and on investigations of their
      unique properties. In the past few decades, inspired by the lotus leaf, the
      discovery of nano- and micro-hierarchical structures has brought about great
      change in the superhydrophobic nanocoatings field. In this paper we review the
      contributions to this field reported in recent literature, mainly including
      materials, fabrication and applications. In order to facilitate comparison,
      materials are divided into 3 categories as follows: inorganic materials, organic
      materials, and inorganic-organic materials. Each kind of materials has itself
      merits and demerits, as well as fabrication techniques. The process of each
      technique is illustrated simply through a few classical examples. There is, to
      some extent, an association between various fabrication techniques, but many are
      different. So, it is important to choose appropriate preparation strategies,
      according to conditions and purposes. The peculiar properties of superhydrophobic
      nanocoatings, such as self-cleaning, anti-bacteria, anti-icing, corrosion
      resistance and so on, are the most dramatic. Not only do we introduce application
      examples, but also try to briefly discuss the principle behind the phenomenon.
      Finally, some challenges and potential promising breakthroughs in this field are
      also succinctly highlighted. 

PMID- 25766487
TI  - A new model of tethered cord syndrome produced by slow traction.
AB  - The development of a suitable animal model is important for clarifying the
      pathogenesis of tethered cord syndrome (TCS). This study was undertaken to
      develop a new animal model for investigating the pathogenesis and therapeutic
      strategies for TCS. A traction device, a filum terminale tractor, was designed
      exclusively for this experiment. A TCS model was produced in cats using the
      tractor to fixate the filum terminale to the dorsal aspect of the second sacrum.
      The responses to tethering were evaluated by electron microscopy and
      electromyography for detection of somatosensory evoked potentials (SEPs) and
      motor evoked potentials (MEPs) at designated time points. Progressive swaying
      gait and lameness in clinical performance were observed with cord traction.
      Histopathological examination revealed an association between the increasing
      traction in the spinal cord and the increase in impaired nerve cells. No changes
      of SEPs and MEPs were detected in the untethered cats, while the latencies of
      SEPs and MEPs significantly increased in the tethered cats. The TCS model
      established in this study is simple and reproducible, in which varying degrees of
      tension could be applied to the neural elements. 

PMID- 25766488
TI  - Pharmacogenetic profile of a South Portuguese population: results from the pilot
      study of the European Health Examination Survey in Portugal.
AB  - BACKGROUND: The genetic inter-individual variability of drug response can lead to
      therapeutic failure or adverse drug reactions (ADRs). The aims of this study were
      to assess the pharmacogenetic profile of a South Portuguese population according
      to established dosing guidelines for commonly prescribed drugs and to compare it
      with that of previously genotyped populations. METHODS: A cross-sectional study
      was developed in the context of the Portuguese Component of the European Health
      Examination Survey (EHES). A total of 47 pharmacogenetically relevant variants in
      23 different genes were genotyped in 208 participants. Allelic and genotypic
      frequencies were calculated, and the pharmacogenetic profile of the participants
      was defined. A comparative analysis was conducted through electronic database
      search. Pairwise Fst calculations were performed to assess the genetic distance
      between populations. RESULTS: We found a significant small differentiation
      between the Portuguese regional populations regarding CYP2C9 rs1057910, CYP2D6
      rs3892097, MTHFR rs1801133 and F5 rs6025. When consid-ering 4 HapMap populations,
      ADH1B rs2066702, ADH1B rs1229984, NAT2 rs1799931 and VKORC1 rs9923231 displayed a
      significant population differentiation. We found that 18.9% of the participants
      are intermediate or poor metabolizers for at least 3 drugs simultaneously and
      that 84.6% of the participants have at least one therapeutic failure or ADR risk
      allele for the considered drugs. CONCLUSIONS: There is a high prevalence of risk
      alleles associated with an altered drug metabolism regarding drugs largely used
      by the South Portuguese population. This knowledge contributes to the prediction
      of their clinical efficacy and/or toxicity, optimizing therapeutic response while
      improving cost-effectiveness.

PMID- 25766489
TI  - DIRECT secure messaging as a common transport layer for reporting structured and
      unstructured lab results to outpatient providers.
AB  - This report describes a grant-funded project to explore the use of DIRECT secure
      messaging for the electronic delivery of laboratory test results to outpatient
      physicians and electronic health record systems. The project seeks to leverage
      the inherent attributes of DIRECT secure messaging and electronic provider
      directories to overcome certain barriers to the delivery of lab test results in
      the outpatient setting. The described system enables laboratories that generate
      test results as HL7 messages to deliver these results as structured or
      unstructured documents attached to DIRECT secure messages. The system
      automatically analyzes generated HL7 messages and consults an electronic provider
      directory to determine the appropriate DIRECT address and delivery format for
      each indicated recipient. The system also enables lab results delivered to
      providers as structured attachments to be consumed by HL7 interface engines and
      incorporated into electronic health record systems. Lab results delivered as
      unstructured attachments may be printed or incorporated into patient records as
      PDF files. The system receives and logs acknowledgement messages to document the
      status of each transmitted lab result, and a graphical interface allows searching
      and review of this logged information. The described system is a fully
      implemented prototype that has been tested in a laboratory setting. Although this
      approach is promising, further work is required to pilot test the system in
      production settings with clinical laboratories and outpatient provider
      organizations. 

PMID- 25766490
TI  - Autonomous motivation is associated with hearing aid adoption.
AB  - OBJECTIVE: To use the self-determination theory of motivation to investigate
      whether different forms of motivation were associated with adults' decisions
      whether or not to adopt hearing aids. DESIGN: A quantitative approach was used in
      this cohort study. Participants completed the treatment self-regulation
      questionnaire (TSRQ), which measured autonomous and controlled motivation for
      hearing aid adoption. Sociodemographic data and audiometric information were also
      obtained. STUDY SAMPLE: Participants were 253 adults who had sought information
      about their hearing but had not consulted with a hearing professional.
      Participants were categorized as hearing aid adopters if they had been fitted
      with hearing aids 4-6 months after completing the TSRQ, and as non-adopters if
      they had not. RESULTS: Multivariate logistic regression was used to examine
      associations between autonomous and controlled motivation, sociodemographic and
      audiometric variables, and hearing aid adoption (n = 160). Three factors were
      significantly associated with increased hearing aid adoption when the influence
      of other variables was accounted for: autonomous motivation, perceived hearing
      difficulty, and poorer hearing. Controlled motivation was not found to influence
      hearing aid adoption. CONCLUSION: These empirical findings that link autonomous
      motivation to decisions of hearing help-seekers have implications for the ways
      practitioners may evaluate motivation and could inform discussions with clients
      about hearing aid adoption.

PMID- 25766491
TI  - Long-term electrode impedance changes and failure prevalence in cochlear
      implants.
AB  - OBJECTIVE: This study assessed the prevalence of electrode failures and electrode
      impedance measures in Nucleus cochlear implants around initial activation (an
      average of 16 days after surgery) and after 8 to 12 years of device use. DESIGN:
      Retrospective data from the Melbourne Cochlear Implant Clinic was collated and
      analysed. STUDY SAMPLE: Included in this study were 232 adults, all of whom were
      implanted at the clinic between March 1998 and August 2005. RESULTS: Overall 0.5%
      of electrodes failed over the entire test period, with 5.6% of devices showing
      one or more electrode failure. The majority of these failures were recorded by
      initial activation. The numbers of electrode failures have decreased over time
      with array type, such that no failures were recorded with the currently available
      Contour Advance array. Array type was shown to affect electrode impedance at both
      time points, with the Contour and Contour Advance arrays having significantly
      higher absolute values than the Banded array. However, the Banded array had
      significantly higher area-normalized impedances at initial and final measures
      than the Contour and Contour Advance array. CONCLUSIONS: A relatively low
      incidence of electrode failures were recorded for the Nucleus devices of these
      recipients. Electrode impedance dropped for all array types after 8 to 12 years
      of device use.

PMID- 25766492
TI  - Identifying a context-effective school hearing screening test: An emic/etic
      framework.
AB  - OBJECTIVE: To identify a context-effective hearing screening test for primary
      schools in the Western Cape, South Africa using an emic-etic framework for test
      selection. DESIGN: A sequential mixed methods design was used to: (1) Identify
      test properties needed to successfully screen hearing in primary school children
      in the Western Cape, (2) select the hearing screening test most likely to succeed
      in this context, and (3) assess the use of the test in context. STUDY SAMPLE:
      Three nurses, two nursing assistants, two paediatric audiologists, and 100 grade
      one children participated. RESULTS: Distortion product otoacoustic emissions
      (DPOAEs) were identified as the test most likely to succeed as a hearing
      screening test in primary school children in the Western Cape. While school
      nurses were able to successfully apply OAE testing in this context, its
      sensitivity to hearing loss in these children was 57.14%. CONCLUSIONS: The
      sensitivity would need to be improved before OAE testing could be used as a
      context-effective screening test for primary school children in the Western Cape.
      The study demonstrated the value of collaborative program planning using an emic
      etic framework to ensure that screening tests are contextually appropriate.

PMID- 25766493
TI  - Investigating the association between tinnitus severity and symptoms of
      depression and anxiety, while controlling for neuroticism, in a large middle-aged
      UK population.
AB  - OBJECTIVE: Clinical studies indicate increased risk for depression and anxiety
      among tinnitus patients. However population data are scarce, and no studies have
      controlled for neuroticism. We examined associations between tinnitus and
      symptoms of depression and anxiety in a large UK population, controlling for
      neuroticism, to explore whether neuroticism, as previously reported, fully
      explains the association between symptoms of depression and anxiety, and
      tinnitus. DESIGN: We used the UK Biobank resource. STUDY SAMPLE: 171 728
      participants answered hearing questions. RESULTS: Using generalized linear
      modelling, we examined associations between tinnitus (mild to severe) and
      symptoms of depression and anxiety. Controlling for neuroticism, patients with
      severe tinnitus were at increased risk of depression (odds ratio (OR) = 1.27) and
      anxiety (OR = 1.11) symptoms, compared to those without tinnitus. CONCLUSIONS:
      Although it is not possible to determine whether tinnitus is a predisposing
      factor to depression, these results suggest an association. We suggest further
      exploration to determine the clinical significance of this association. Early
      psychosocial intervention aimed at reducing anxiety and depression in patients at
      increased risk might influence the extent to which tinnitus is experienced as
      troubling, and therefore psychological distress associated with it. Likewise,
      with tinnitus patients, assessment for anxiety/depression should be considered.

PMID- 25766494
TI  - Correct assignment of lipophilic dye mixtures? A case study for high-performance
      thin-layer chromatography-mass spectrometry and performance data for the TLC-MS
      Interface.
AB  - The TLC-MS Interface, the successor of the ChromeXtract, has been available for
      elution head-based coupling of high-performance thin-layer chromatography with
      mass spectrometry (HPTLC-MS) since 2009, and is meanwhile widespread in use,
      mainly for compound confirmation. Until now, quantitative performance data has
      not been reported in detail and thus were investigated in this study. The
      performance data of HPTLC-electrospray ionization (ESI)-MS via the TLC-MS
      Interface showed good mean precisions (%RSD, n=5) for 6 dyes in a commercially
      available dye mixture investigated at two different concentrations (7.3% for the
      1:8 dilution, and 10.1% for the 1:16 diluted) in a selected worst case scenario.
      The respective mean precisions of absorbance measurements were <=1.3%. For
      calibrations by HPTLC-ESI-MS, the mean determination coefficient was 0.9975 for
      the 6 dyes (versus 0.9997 for absorbance measurement). HPTLC-MS analysis revealed
      the incorrect assignment of components in two commercially available dye
      mixtures. Using an additional software (MassWorks) that delivered a 100 times
      increased mass accuracy, the proposal of molecular formulae was shown to be
      obtainable under certain conditions with a low resolution single quadrupole mass
      spectrometer and in the case of helpful information such as the double bond
      equivalents. This enabled the identification of the incorrectly assigned unknown
      dyes and clearly demonstrated the benefit of using HPTLC-MS for zone
      confirmation. 

PMID- 25766495
TI  - Investigation, comparison and design of chambers used in centrifugal partition
      chromatography on the basis of flow pattern and separation experiments.
AB  - In centrifugal partition chromatography (CPC) the separation efficiency is mainly
      influenced by the hydrodynamic of mobile and stationary phase in the chambers.
      Thus, the hydrodynamic has to be investigated and understood in order to enhance
      a CPC separation run. Different chamber geometries have been developed in the
      past and the influence of several phase systems and CPC operating conditions were
      investigated for these chambers. However, a direct comparison between the
      different chamber types has not been performed yet. In order to investigate the
      direct influence of the chamber design on the hydrodynamic, several chamber
      designs - partially similar in geometry to commercial available designs - are
      investigated under standardized conditions in the present study. The results show
      the influence of geometrical aspects of the chamber design on the hydrodynamic
      and therewith, on the separation efficiency. As a conclusion of the present
      study, some ideas for an optimal chamber design for laboratory and industrial
      purpose are proposed. 

PMID- 25766496
TI  - Analysis of volatile phenols in alcoholic beverage by ethylene glycol
      polydimethylsiloxane based stir bar sorptive extraction and gas chromatography
      mass spectrometry.
AB  - An ethylene glycol (EG)/polydimethylsiloxane (PDMS) copolymer based stir bar
      sorptive extraction (SBSE)-GC-MS method was developed for the analysis of
      volatile phenols (4-ethylphenol, 4-vinylphenol, 4-ethylguaiacol, and 4
      vinylguaiacol) in alcoholic beverages. The beverage samples were diluted with
      phosphate buffer (1M, pH 7) and extracted with an EG/PDMS stir bar. Volatile
      phenols were thermally desorbed and analyzed by GC-MS. Parameters affecting
      extraction efficiency were studied including ionic strength, pH, extraction time,
      ethanol content and nonvolatile matrix. Good correlation coefficients with R(2)
      in the range of 0.994-0.999 were obtained for volatile phenol concentration of 5
      500MUg/L. Recovery for all phenols were from 95.7% to 104.4% in a beer matrix and
      81.4% to 97.6% in a wine matrix. The method had a standard deviation less than
      5.8% for all volatile phenols. The limit of quantification (LOQs) in beer samples
      was lower than 3MUg/L. The method was further applied to analyze the
      concentrations of volatile phenols in beer, wine and other alcoholic beverage
      samples. 

PMID- 25766497
TI  - Incidence of primary hypertension in a population-based cohort of HIV-infected
      compared with non-HIV-infected persons and the effect of combined antiretroviral
      therapy.
AB  - Literature remains scarce on the impact of antiretroviral medications on
      hypertension in the HIV population. We used the South Carolina Medicaid database
      linked with the enhanced HIV/AIDS system surveillance database for 1994-2011 to
      evaluate incident hypertension and the impact of combination antiretroviral
      therapy (cART) in HIV/AIDS population compared with a propensity- matched non-HIV
      control group. Multivariable, time-dependent survival analysis suggested no
      significant difference in incidence of hypertension between the HIV group and the
      non-HIV control group. However, subgroup analysis suggested that among the HIV
      infected group, months of exposure to both non-nucleoside reverse transcriptase
      inhibitors (adjusted hazard ratio, 1.52; 95% confidence interval, 1.3-1.75) and
      protease inhibitors (adjusted hazard ratio, 1.26; 95% confidence interval, 1.11
      1.44) were associated with an increased risk of incident hypertension after
      adjusting for traditional demographic and metabolic risk factors. In people with
      HIV/AIDS, prolonged exposure to both protease inhibitor-based and non-nucleoside
      reverse transcriptase inhibitor-based cART may increase the risk of incident
      hypertension.

PMID- 25766498
TI  - Risk factor panels associated with hypertension in obstructive sleep apnea
      patients with different body mass indexes.
AB  - Although hypertension (HTN), obstructive sleep apnea (OSA), and obesity
      frequently co-occur, the precise role of obesity in this interrelationship is not
      completely understood. A total of 727 OSA patients were assigned to body mass
      index (BMI) <25 (27.6%; n = 201), 25<= BMI <29.99 (53.4%; n = 388), and BMI >=30
      (19%; n = 138). HTN risk factors in each group were evaluated. A total of 244
      (33.6%) patients exhibited co-morbid HTN, of whom 20.5% (50/244), 52.9%
      (129/244), and 26.6% (65/244) were distributed between the BMI <25, 25<= BMI
      <29.99, and BMI >=30 groups, respectively. Multiple logistic regression indicated
      that age, male gender, triglycerides (TG), low-density lipoprotein cholesterol
      (LDL-C), and apnea-hypopnea index (AHI) scores were HTN risk factors for the
      BMI<25 group. In the 25<= BMI <29.99 group, risk factors were age, BMI, diabetes,
      and AHI. Finally, in the BMI >=30 group, risk factors were age, diabetes, TG, LDL
      C and AHI. These results demonstrate that different risk factor panels were
      associated with HTN in OSA patients with different BMIs.

PMID- 25766499
TI  - Ileo-colonic intussusception.

PMID- 25766500
TI  - Di-(2-ethylhexyl)-phthalate induces oxidative stress in human endometrial stromal
      cells in vitro.
AB  - Di-(2-ethylhexyl)-phthalate (DEHP) accumulates in the environment, and its
      exposure is possibly associated with endocrine-related disease in women of
      reproductive age. The effects of DEHP on human endometrial cells are unknown. We
      treated human endometrial stromal cells with 10, 100, and 1000 pmol of DEHP and
      measured reactive oxygen species (ROS) generation, expression levels of
      antioxidant enzymes, alteration of MAPK/NF-kappaB signaling and hormonal
      receptors. DEHP increased reactive oxygen species (ROS) generation and decreased
      expression of superoxide dismutase (SOD), glutathione peroxidase (GPX), heme
      oxygenase (HO), and catalase (CAT). By DEHP exposure, p-ERK/p-p38 and NF-kappaB
      mediated transcription was increased. Additionally, DEHP induced estrogen
      receptor-alpha (ER-alpha) expression in a dose-dependent manner. This study shows
      the need for future mechanistic studies of oxidative stress, MAPK/NF-kappaB
      signaling, and ER-alpha as molecular mediators of DEHP-associated endometrial
      stromal cell alterations, which may be associated with the development of
      endocrine-related disease such as endometriosis.

PMID- 25766501
TI  - Novel activating mutation of human calcium-sensing receptor in a family with
      autosomal dominant hypocalcaemia.
AB  - INTRODUCTION: Autosomal dominant hypocalcaemia (ADH) is caused by activating
      mutations in the calcium sensing receptor gene (CaR) and characterised by mostly
      asymptomatic mild to moderate hypocalcaemia with low, inappropriately serum
      concentration of PTH. OBJECTIVE: The purpose of the present study was to
      biochemically and functionally characterise a novel mutation of CaR. PATIENTS: A
      female proband presenting with hypocalcaemia was diagnosed to have "idiopathic
      hypoparathyroidism" at the age of 10 with a history of muscle pain and cramps.
      Further examinations demonstrated hypocalcaemia in nine additional family
      members, affecting three generations. MAIN OUTCOME MEASURE: P136L CaR mutation
      was predicted to cause gain of function of CaR. RESULTS: Affected family members
      showed relevant hypocalcaemia (mean +/- SD; 1.9 +/- 0.1 mmol/l). Patient history
      included mild seizures and recurrent nephrolithiasis. Genetic analysis confirmed
      that hypocalcaemia cosegregated with a heterozygous mutation at codon 136 (CCC ->
      CTC/Pro -> Leu) in exon 3 of CaR confirming the diagnosis of ADH. For in vitro
      studies P136L mutant CaR was generated by site-directed mutagenesis and examined
      in transiently transfected HEK293 cells. Extracellular calcium stimulation of
      transiently transfected HEK293 cells showed significantly increased intracellular
      Ca(2+) mobilisation and MAPK activity for mutant P136L CaR compared to wild type
      CaR. CONCLUSIONS: The present study gives insight about a novel activating
      mutation of CaR and confirms that the novel P136L-CaR mutation is responsible for
      ADH in this family.

PMID- 25766502
TI  - Bradykinin-activated contractile signalling pathways in human myometrial cells
      are differentially regulated by arrestin proteins.
AB  - Bradykinin is associated with infections and inflammation, which given the strong
      correlation between uterine infection and preterm labour may imply that it could
      play a role in this process. Therefore, we investigated bradykinin signalling,
      and the roles that arrestin proteins play in their regulation in human myometrial
      cells. Bradykinin induced rapid, transient intracellular Ca(2+) increases that
      were inhibited following B2 receptor (B2R) antagonism. Arrestin2 or arrestin3
      depletion enhanced and prolonged bradykinin-stimulated Ca(2+) responses, and
      attenuated B2R desensitisation. Knockdown of either arrestin enhanced B2R
      stimulated ERK1/2 signals. Moreover, depletion of either arrestin elevated peak
      phase p38-MAPK signalling, yet only arrestin3 depletion prolonged B2R-induced p38
      MAPK signals. Arrestin2-knockdown augmented bradykinin-induced cell movement.
      Bradykinin stimulates pro-contractile signalling mechanisms in human myometrial
      cells and arrestin proteins play key roles in their regulation. Our data suggest
      bradykinin not only acts as an utertonin, but may also have the potential to
      enhance the contractile environment of the uterus. 

PMID- 25766503
TI  - Silencing Mediator of Retinoid and Thyroid Hormone Receptors (SMRT) regulates
      glucocorticoid action in adipocytes.
AB  - Local modulation of glucocorticoid action in adipocytes regulates adiposity and
      systemic insulin sensitivity. However, the specific cofactors that mediate
      glucocorticoid receptor (GR) action in adipocytes remain unclear. Here we show
      that the silencing mediator of retinoid and thyroid hormone receptors (SMRT) is
      recruited to GR in adipocytes and regulates ligand-dependent GR function.
      Decreased SMRT expression in adipocytes in vivo increases expression of
      glucocorticoid-responsive genes. Moreover, adipocytes with decreased SMRT
      expression exhibit altered glucocorticoid regulation of lipolysis. We conclude
      that SMRT regulates the metabolic functions of GR in adipocytes in vivo.
      Modulation of GR-SMRT interactions in adipocytes represents a novel approach to
      control the local degree of glucocorticoid action and thus influence adipocyte
      metabolic function. 

PMID- 25766504
TI  - Catalytic asymmetric addition of Meldrum's acid, malononitrile, and 1,3
      dicarbonyls to ortho-quinone methides generated in situ under basic conditions.
AB  - A new approach to the utilization of highly reactive and unstable ortho-quinone
      methides (o-QMs) in catalytic asymmetric settings is presented. The
      enantioselective reactions are catalysed by bifunctional organocatalysts, and the
      o-QM intermediates are formed in situ from 2-sulfonylalkyl phenols through base
      promoted elimination of sulfinic acid. The use of mild Bronsted basic conditions
      for transiently generating o-QMs in catalytic asymmetric processes is
      unprecedented, and allows engaging productively in the reactions nucleophiles
      such as Meldrum's acid, malononitrile and 1,3-dicarbonyls. The catalytic
      transformations give new and general entries to 3,4-dihydrocoumarins, 4H
      chromenes and xanthenones. These frameworks are recurring structures in natural
      product and medicinal chemistry, as testified by the formal syntheses of (R)
      tolterodine and (S)-4-methoxydalbergione from the catalytic adducts. 

PMID- 25766505
TI  - Percentage Change in Plasma Cytokeratin 18 Is Associated with Clinical Outcomes
      in Patients Receiving Pemetrexed and Carboplatin for the Adenocarcinoma Subtype
      of NSCLC.
AB  - BACKGROUND: The adenocarcinoma subtype of non-small cell lung cancer (adeno
      NSCLC) is routinely treated with chemotherapy if patients do not have molecular
      aberrations such as epidermal growth factor receptor mutations or anaplastic
      lymphoma kinase rearrangements. There are currently no validated biomarkers that
      can predict if patients will gain clinical benefit from chemotherapy, leading to
      a majority of patients receiving many cycles of unnecessary chemotherapy. We
      hypothesized that the percentage rise in plasma caspase-cleaved cytokeratin 18
      (cCK18) and total cytokeratin 18 (tCK18) assessed before and after chemotherapy
      correlates with the radiological response to chemotherapy. METHODS: Plasma
      samples from 40 patients with stage IV adeno-NSCLC, treated with first-line
      chemotherapy with carboplatin (AUC5) plus pemetrexed (500 mg/m(2)), were
      collected prior to chemotherapy and 48 h after treatment. ELISA was used to
      quantify cCK18 and tCK18. RESULTS: The male-to-female ratio was 3:1, and the
      median age of patients was 63 years. Patients who had a clinical benefit
      (complete response, partial response or stable disease) at the first radiological
      assessment following chemotherapy had a significantly higher percentage change in
      plasma tCK18 levels compared to those who had no clinical benefit, i.e.
      progressive disease (69.5 +/- 75.1 vs. 25.3 +/- 30.9%, respectively; p = 0.042).
      The receiver operating characteristic area was 0.712 (p = 0.039). There was an
      increase in the percentage change in cCK18 in patients with clinical benefit
      compared to those without clinical benefit but this was not statistically
      significant (57.6 +/- 112.8 vs. 24.38 +/- 45.1%, respectively; p = 0.85).
      CONCLUSIONS: The percentage change in plasma tCK18 levels before and after the
      first cycle of pemetrexed and carboplatin chemotherapy is associated with
      clinical benefit. If validated in larger cohorts, this test can be used to
      identify patients unlikely to respond to treatment who can thus be offered
      alternative treatments or entry into clinical trials.

PMID- 25766506
TI  - Optimal Analysis to Discriminate Males' Osteoporosis With Simple Physiological
      Indicators: A Cutoff Point Study.
AB  - Males account for one third of global hip fracture patients, and their hip
      fracture-related mortality rate is higher than that of females. Scholars have
      primarily investigated self-evaluation indicators for elderly Caucasians and
      other ethnicities, and have rarely conducted large-scale cutoff point studies on
      Asian males. In this study, a large-scale database on bone mineral density (BMD)
      examinations was used to conduct a cutoff point study on males with osteoporosis.
      This study involved a retrospective research design. Males who accepted BMD
      examinations from 2009 to 2012 at a large teaching hospital in Taiwan were
      sampled in this study. This study used the database for analyzing effects with
      using osteoporosis self-assessment indicator, age, body weight, and body mass
      index (BMI) to discriminate osteoporosis in males, specifically focusing on
      accuracy, cutoff point, sensitivity, specificity, and positive and negative
      predictive values. Overall, receiver operating characteristic curve for the
      samples reached 70%. These cutoff points included: a body weight is less than
      58.8 kg, BMI is 23 kg/m2, and the osteoporosis self-assessment score is -1.86, to
      identify osteoporosis. Involving body weight and BMI as optimal assessing
      indicators for assessing osteoporosis among males younger than 65 years, and the
      osteoporosis self-assessment tool was ideal for measuring males older than 65
      years. Professional health staff should apply convenient, low-cost, and accurate
      evaluation tools that can assist Asian males in planning preventive osteoporosis
      strategies to avoid osteoporotic fractures and death.

PMID- 25766507
TI  - Past-day recall of sedentary time: Validity of a self-reported measure of
      sedentary time in a university population.
AB  - OBJECTIVES: To assess the validity of the Past-day Adults' Sedentary Time
      University (PAST-U) questionnaire, modified for a university population, compared
      with activPAL. DESIGN: Participants (n=57, age=18-55 years, 47% female, 65%
      students) were recruited from the University of Queensland (students and staff).
      METHODS: Participants answered the PAST-U questionnaire, which asked about time
      spent sitting or lying down for work, study, travel, television viewing, leisure
      time computer use, reading, eating, socialising and other purposes, during the
      previous day. Times reported for these questions were summed to provide a measure
      of total sedentary time. Participants also wore an activPAL device for the full
      day prior to completing the questionnaire and recorded their wake and sleep times
      in an activity log. Total waking sedentary time derived from the activPAL was
      used as the criterion measure. Correlation (intraclass correlation coefficient,
      ICC) and agreement (Bland-Altman plots) between PAST-U and activPAL sedentary
      time were examined. RESULTS: Participants were sedentary (activPAL-determined)
      for 66% of waking hours. The correlation between PAST-U and activPAL sedentary
      time for the whole sample was ICC=0.64 [95% confidence interval (CI)=0.45, 0.77];
      and higher for non-students (ICC=0.78, 95%CI 0.52, 0.91) than students (ICC=0.59,
      95%CI 0.33, 0.77). Bland-Altman plots revealed that the mean difference between
      the two measures was 5min although limits of agreement were wide (95% limits of
      agreement: -3.9 to 4.1h). CONCLUSIONS: The PAST-U provides an acceptable measure
      of sedentary time in this population, which included students and adults with
      high workplace sitting time.

PMID- 25766508
TI  - Associations between organized sports participation and objectively measured
      physical activity, sedentary time and weight status in youth.
AB  - OBJECTIVES: The purpose of this study was to examine whether participation in
      organized sports is related to achieving physical activity recommendations, body
      mass index (BMI), objectively measured PA intensity and time spent sedentary.
      DESIGN: Cross-sectional study. METHODS: The sample comprised 973 children and
      adolescents (427 boys, 546 girls) aged 10-18 years (Mage=14.1+/-2.4). Organized
      sport was self-reported. Physical activity and time spent in moderate and
      vigorous intensity PA (MVPA) and sedentary time was assessed with accelerometers.
      RESULTS: More boys (51.3%) than girls (28.3%) reported to be involved in
      organized sports participation (p<0.001). Those who were engaged in organized
      sports were more likely to achieve physical activity guidelines (OR=1.64, 95% CI:
      1.14-2.35, p<0.01), spent more time in MPA (OR=1.01, 95% CI: 1.01-1.02, p<0.01),
      VPA (OR=1.09, 95% CI: 1.05-1.13, p<0.001), and MVPA (OR=1.01, 95% CI: 1.01-1.02,
      p<0.001) than those who did not participate in organized sports. No associations
      between organised sport participation and time spent sedentary or BMI was
      observed. CONCLUSIONS: Engagement in organized sports is related to higher levels
      of objectively measured MPA, VPA and achieving the recommended levels of MVPA in
      youth; however participation in sports appears unrelated to time spent sedentary
      and BMI. Our results suggest that promoting organised sport may increase physical
      activity of at least moderate intensity in young people.

PMID- 25766509
TI  - Plyometric training improves voluntary activation and strength during isometric,
      concentric and eccentric contractions.
AB  - OBJECTIVES: This study investigated effects of plyometric training (6 weeks, 3
      sessions/week) on maximum voluntary contraction (MVC) strength and neural
      activation of the knee extensors during isometric, concentric and eccentric
      contractions. DESIGN: Twenty-seven participants were randomly assigned to the
      intervention or control group. METHODS: Maximum voluntary torques (MVT) during
      the different types of contraction were measured at 110 degrees  knee flexion
      (180 degrees =full extension). The interpolated twitch technique was applied at
      the same knee joint angle during isometric, concentric and eccentric contractions
      to measure voluntary activation. In addition, normalized root mean square of the
      EMG signal at MVT was calculated. The twitch torque signal induced by electrical
      nerve stimulation at rest was used to evaluate training-related changes at the
      muscle level. In addition, jump height in countermovement jump was measured.
      RESULTS: After training, MVT increased by 20Nm (95% CI: 5-36Nm, P=0.012), 24Nm
      (95% CI: 9-40Nm, P=0.004) and 27Nm (95% CI: 7-48Nm, P=0.013) for isometric,
      concentric and eccentric MVCs compared to controls, respectively. The strength
      enhancements were associated with increases in voluntary activation during
      isometric, concentric and eccentric MVCs by 7.8% (95% CI: 1.8-13.9%, P=0.013),
      7.0% (95% CI: 0.4-13.5%, P=0.039) and 8.6% (95% CI: 3.0-14.2%, P=0.005),
      respectively. Changes in the twitch torque signal of the resting muscle, induced
      by supramaximal electrical stimulation of the femoral nerve, were not observed,
      indicating no alterations at the muscle level, whereas jump height was increased.
      CONCLUSIONS: Given the fact that the training exercises consisted of eccentric
      muscle actions followed by concentric contractions, it is in particular relevant
      that the plyometric training increased MVC strength and neural activation of the
      quadriceps muscle regardless of the contraction mode.

PMID- 25766510
TI  - Diagnosing infection with small ruminant lentiviruses of genotypes A and B by
      combining synthetic peptides in ELISA.
AB  - The major challenges in diagnosing small ruminant lentivirus (SRLV) infection
      include early detection and genotyping of strains of epidemiological interest. A
      longitudinal study was carried out in Rasa Aragonesa sheep experimentally
      infected with viral strains of genotypes A or B from Spanish neurological and
      arthritic SRLV outbreaks, respectively. Sera were tested with two commercial
      ELISAs, three based on specific peptides and a novel combined peptide ELISA.
      Three different PCR assays were used to further assess infection status. The
      kinetics of anti-viral antibody responses were variable, with early diagnosis
      dependent on the type of ELISA used. Peptide epitopes of SRLV genotypes A and B
      combined in the same ELISA well enhanced the overall detection rate, whereas
      single peptides were useful for genotyping the infecting strain (A vs. B). The
      results of the study suggest that a combined peptide ELISA can be used for
      serological diagnosis of SRLV infection, with single peptide ELISAs useful for
      subsequent serotyping.

PMID- 25766511
TI  - Social odors conveying dominance and reproductive information induce rapid
      physiological and neuromolecular changes in a cichlid fish.
AB  - BACKGROUND: Social plasticity is a pervasive feature of animal behavior. Animals
      adjust the expression of their social behavior to the daily changes in social
      life and to transitions between life-history stages, and this ability has an
      impact in their Darwinian fitness. This behavioral plasticity may be achieved
      either by rewiring or by biochemically switching nodes of the neural network
      underlying social behavior in response to perceived social information.
      Independent of the proximate mechanisms, at the neuromolecular level social
      plasticity relies on the regulation of gene expression, such that different
      neurogenomic states emerge in response to different social stimuli and the
      switches between states are orchestrated by signaling pathways that interface the
      social environment and the genotype. Here, we test this hypothesis by
      characterizing the changes in the brain profile of gene expression in response to
      social odors in the Mozambique Tilapia, Oreochromis mossambicus. This species has
      a rich repertoire of social behaviors during which both visual and chemical
      information are conveyed to conspecifics. Specifically, dominant males increase
      their urination frequency during agonist encounters and during courtship to
      convey chemical information reflecting their dominance status. RESULTS: We
      recorded electro-olfactograms to test the extent to which the olfactory
      epithelium can discriminate between olfactory information from dominant and
      subordinate males as well as from pre- and post-spawning females. We then
      performed a genome-scale gene expression analysis of the olfactory bulb and the
      olfactory cortex homolog in order to identify the neuromolecular systems involved
      in processing these social stimuli. CONCLUSIONS: Our results show that different
      olfactory stimuli from conspecifics' have a major impact in the brain
      transcriptome, with different chemical social cues eliciting specific patterns of
      gene expression in the brain. These results confirm the role of rapid changes in
      gene expression in the brain as a genomic mechanism underlying behavioral
      plasticity and reinforce the idea of an extensive transcriptional plasticity of
      cichlid genomes, especially in response to rapid changes in their social
      environment.

PMID- 25766512
TI  - In-hospital management and outcomes of acute coronary syndromes in relation to
      prior history of heart failure.
AB  - INTRODUCTION: The prognostic significance of prior heart failure in acute
      coronary syndromes has not been well studied. Accordingly, we evaluated the
      baseline characteristics, management patterns and clinical outcomes in patients
      with acute coronary syndromes who had prior heart failure. METHODS AND RESULTS:
      The study population consisted of acute coronary syndrome patients in the Global
      Registry of Acute Coronary Events, expanded Global Registry of Acute Coronary
      Events and Canadian Registry of Acute Coronary Events between 1999 and 2008. Of
      the 13,937 eligible patients (mean age 66+/-13 years, 33% female and 28.3% with
      ST-elevation myocardial infarction), 1498 (10.7%) patients had a history of heart
      failure. Those with prior heart failure tended to be older, female and had lower
      systolic blood pressure, higher Killip class and creatinine on presentation.
      Prior heart failure was also associated with significantly worse left ventricular
      systolic function and lower rates of cardiac catheterization and coronary
      revascularization. The group with previous heart failure had significantly higher
      rates of acute decompensated heart failure, cardiogenic shock, myocardial
      (re)infarction and mortality in hospital. In multivariable analysis, prior heart
      failure remained an independent predictor of in-hospital mortality (odds ratio
      1.48, 95% confidence interval 1.08-2.03, p=0.015). CONCLUSIONS: Prior heart
      failure was associated with high risk features on presentation and adverse
      outcomes including higher adjusted in-hospital mortality in acute coronary
      syndrome patients. However, acute coronary syndrome patients with prior heart
      failure were less likely to receive evidence-based therapies, suggesting
      potential opportunities to target more intensive treatment to improve their
      outcome.

PMID- 25766513
TI  - Efficacy of cardiopulmonary rehabilitation with adaptive servo-ventilation in
      patients undergoing off-pump coronary artery bypass grafting.
AB  - BACKGROUND: Postoperative complications after cardiac surgery increase mortality.
      This study aimed to evaluate the efficacy of cardiopulmonary rehabilitation with
      adaptive servo-ventilation (ASV) in patients undergoing off-pump coronary artery
      bypass grafting (OPCAB). METHODS AND RESULTS: A total of 66 patients undergoing
      OPCAB were enrolled and divided into 2 groups according to the use of ASV (ASV
      group, 30 patients; non-ASV group, 36 patients). During the perioperative period,
      all patients undertook cardiopulmonary rehabilitation. ASV was used from
      postoperative day (POD) 1 to POD5. Hemodynamics showed a different pattern in the
      2 groups. Blood pressure (BP) on POD6 in the ASV group was significantly lower
      than that in the non-ASV group (systolic BP, 112.9+/-12.6 vs. 126.2+/-15.8 mmHg,
      P=0.0006; diastolic BP, 62.3+/-9.1 vs. 67.6+/-9.3 mmHg, P=0.0277). The incidence
      of postoperative atrial fibrillation (POAF) was lower in the ASV group than in
      the non-ASV group (10% vs. 33%, P=0.0377). The duration of oxygen inhalation in
      the ASV group was significantly shorter than that in the non-ASV group (5.1+/-2.2
      vs. 7.6+/-6.0 days, P=0.0238). The duration of postoperative hospitalization was
      significantly shorter in the ASV group than in the non-ASV group (23.5+/-6.6 vs.
      29.0+/-13.1 days, P=0.0392). CONCLUSIONS: Cardiopulmonary rehabilitation with ASV
      after OPCAB reduces both POAF occurrence and the duration of hospitalization.

PMID- 25766514
TI  - Speckle tracking echocardiography - Quo Vadis?
AB  - Although echocardiography is a noninvasive means of visualizing the heart,
      quantitative and reproducible assessment of myocardial motion remains to be
      established. Tissue Doppler imaging (TDI) emerged in the early 1990 s as a tool
      to measure tissue motion velocity. For the purpose of analyzing regional
      myocardial motion quantitatively, the myocardial velocity gradient (MVG) across
      the myocardial wall was first introduced by using TDI. MVG is mathematically
      equal to strain rate. Initially, strain was derived as the time integral of the
      TDI-derived strain rate, but it revealed substantial errors of measurement, which
      basically arose from the confusion of Eulerian coordinates with Lagrangian
      coordinates in fluid dynamics. Speckle tracking echocardiography (STE) has
      subsequently emerged as a technique that analyzes motion by tracking "speckles"
      on echocardiograms based on Lagrangian coordinates. Although STE-derived strain
      is a robust parameter of myocardial deformation, the stress-strain relationship
      has often been overlooked in the assessment of myocardial function. We should
      consider (1) blood pressure, (2) left ventricular size, and (3) left ventricular
      wall thickness, as well as strain. Practical means of normalizing strain by
      stress should be pursued in the quantitative assessment of myocardial function.
      Consideration of stress-strain relationships is mandatory when interpreting STE
      derived strain.

PMID- 25766515
TI  - Primary stenting in femoropopliteal occlusive disease - what is the appropriate
      role?
AB  - Endovascular treatment of femoropopliteal occlusive disease is challenging and
      often limited by its unique anatomic, hemodynamic and biomechanical constraints.
      Despite technical improvement, percutaneous transluminal angioplasty alone is not
      adequate to provide satisfactory long-term patency. Several randomized controlled
      trials have shown that primary nitinol stenting can provide a better short-term
      radiological patency in intermediate lesion, but the results were often limited
      by intrinsic stent complications, particularly in-stent restenosis. Solutions to
      long lesions have been more elusive. To date, many novel technologies have been
      developed with a goal of improving stent design for this specific environment.
      Interwoven stents are made to provide a higher radial strength and kink
      resistance. Covered stents are designed to prevent the ingrowth of intimal
      hyperplasia, which is the main cause of restenosis in bare metal stent. Drug
      eluting stents have shown improved patency in clinical trials. Bioabsorbable
      stents, combining biological agents and mechanical scaffold, provide temporary
      vascular support while reducing implant-related vascular inflammation in the long
      term. New developments in balloon angioplasty, such as drug elution, provide a
      challenge to stenting in this arena. Although these technologies look promising,
      a uniform reporting system and large-scale comparative studies with longer follow
      up are needed to evaluate their clinical effectiveness in the future.

PMID- 25766516
TI  - Boron nitride nanotube-enhanced osteogenic differentiation of mesenchymal stem
      cells.
AB  - The interaction between boron nitride nanotubes (BNNTs) layer and mesenchymal
      stem cells (MSCs) is evaluated for the first time in this study. BNNTs layer
      supports the attachment and growth of MSCs and exhibits good biocompatibility
      with MSCs. BNNTs show high protein adsorption ability, promote the proliferation
      of MSCs and increase the secretion of total protein by MSCs. Especially, BNNTs
      enhance the alkaline phosphatase (ALP) activity as an early marker of
      osteoblasts, ALP/total protein and osteocalcin (OCN) as a late marker of
      osteogenic differentiation, which shows that BNNTs can enhance osteogenesis of
      MSCs. The release of trace boron and the stress on cells exerted by BNNTs with a
      fiber structure may account for the enhanced differentiation of MSCs into
      osteoblasts. Therefore BNNTs are potentially useful for bone regeneration in
      orthopedic applications.

PMID- 25766517
TI  - Activated Platelets Induce Estrogen Receptor beta Expression in Endometriotic
      Stromal Cells.
AB  - BACKGROUND/AIMS: Endometriosis is viewed first and foremost as an estrogen
      dependent disease, featuring not only excessive estrogen production but also
      aberrant expression of estrogen receptors (ERs), particularly ERbeta, that
      mediate the estrogen action. ERbeta is the predominant ER in mediating estrogen
      action in endometriosis, and estrogen plays a vital role in the development of
      endometriosis; thus, ERbeta is viewed as a strong candidate for therapeutic
      targeting. Given our recent finding that platelets aggregate in endometriotic
      lesions, we sought to investigate whether activated platelets can upregulate
      ERbeta. METHODS: Using primary endometriotic stromal cells derived from patients
      with ovarian endometriomas and platelets harvested from healthy donors, we
      performed real-time RT-PCR analysis of mRNA abundance (n = 8) and Western blot
      analysis of protein expression (n = 8) of ERalpha and ERbeta when co-cultured
      with phosphate-buffered saline, platelets, thrombin alone, and platelets plus
      thrombin for 48 h. RESULTS: Treatment of endometriotic stromal cells with
      activated platelets resulted in the upregulation of ERbeta gene and protein
      expression. CONCLUSION: In the presence of aggregated and thus activated
      platelets in endometriotic lesions, ERbeta, but not ERalpha, is upregulated in
      endometriotic stromal cells. Our result suggests that the use of antiplatelet
      therapy may have potential in the treatment of endometriosis.

PMID- 25766518
TI  - Poly(norepinephrine) as a functional bio-interface for neuronal differentiation
      on electrospun fibers.
AB  - Based on the catecholic chemistry of a mussel inspired coating, norepinephrine
      (NE), a catecholamine found both in neurotransmitters and mussel adhesive
      proteins, was for the first time applied as a unique bio-interface integrating
      multi-functions facilitating PC12 neuron-like differentiation. A uniform, ultra
      smooth pNE coating was achieved on electrospun submicron PLCL fibers, proven by
      surface characterization. The introduced catechol groups from pNE were further
      used to not only anchor collagen to enhance cell adhesion but also localize nerve
      growth factor to promote neuron-like differentiation. The obtained pNE-collagen
      coating was found to be a superior substrate for PC12 differentiation, confirmed
      by both cellular toxicity/viability assays and immunochemical staining. The
      aligned PLCL fiber conformation further steered neurite formation along the fiber
      direction and contributed to neurite extension and increased the number of
      neurites per cell body. This facile pNE coating might lead to a more efficient
      use of growth factor, drugs and other bioactive molecules with lower loading
      dosage and sustained activity resulting in enhanced therapeutic effects and
      decreased adverse effects. 

PMID- 25766519
TI  - Fly-scan ptychography.
AB  - We report an experimental ptychography measurement performed in fly-scan mode.
      With a visible-light laser source, we demonstrate a 5-fold reduction of data
      acquisition time. By including multiple mutually incoherent modes into the
      incident illumination, high quality images were successfully reconstructed from
      blurry diffraction patterns. This approach significantly increases the throughput
      of ptychography, especially for three-dimensional applications and the
      visualization of dynamic systems.

PMID- 25766520
TI  - Learning and memory: Steroids and epigenetics.
AB  - Memory formation and utilization is a complex process involving several brain
      structures in conjunction as the hippocampus, the amygdala and the adjacent
      cortical areas, usually defined as medial temporal lobe structures (MTL). The
      memory processes depend on the formation and modulation of synaptic connectivity
      affecting synaptic strength, synaptic plasticity and synaptic consolidation. The
      basic neurocognitive mechanisms of learning and memory are shortly recalled in
      the initial section of this paper. The effect of sex hormones (estrogens,
      androgens and progesterone) and of adrenocortical steroids on several aspects of
      memory processes are then analyzed on the basis of animal and human studies. A
      specific attention has been devoted to the different types of steroid receptors
      (membrane or nuclear) involved and on local metabolic transformations when
      required. The review is concluded by a short excursus on the steroid activated
      epigenetic mechanisms involved in memory formation. 

PMID- 25766521
TI  - RNASeqBrowser: a genome browser for simultaneous visualization of raw strand
      specific RNAseq reads and UCSC genome browser custom tracks.
AB  - BACKGROUND: Strand specific RNAseq data is now more common in RNAseq projects.
      Visualizing RNAseq data has become an important matter in Analysis of sequencing
      data. The most widely used visualization tool is the UCSC genome browser that
      introduced the custom track concept that enabled researchers to simultaneously
      visualize gene expression at a particular locus from multiple experiments. Our
      objective of the software tool is to provide friendly interface for visualization
      of RNAseq datasets. RESULTS: This paper introduces a visualization tool
      (RNASeqBrowser) that incorporates and extends the functionality of the UCSC
      genome browser. For example, RNASeqBrowser simultaneously displays read coverage,
      SNPs, InDels and raw read tracks with other BED and wiggle tracks -- all being
      dynamically built from the BAM file. Paired reads are also connected in the
      browser to enable easier identification of novel exon/intron borders and
      chimaeric transcripts. Strand specific RNAseq data is also supported by
      RNASeqBrowser that displays reads above (positive strand transcript) or below
      (negative strand transcripts) a central line. Finally, RNASeqBrowser was designed
      for ease of use for users with few bioinformatic skills, and incorporates the
      features of many genome browsers into one platform. CONCLUSIONS: The features of
      RNASeqBrowser: (1) RNASeqBrowser integrates UCSC genome browser and NGS
      visualization tools such as IGV. It extends the functionality of the UCSC genome
      browser by adding several new types of tracks to show NGS data such as individual
      raw reads, SNPs and InDels. (2) RNASeqBrowser can dynamically generate RNA
      secondary structure. It is useful for identifying non-coding RNA such as miRNA.
      (3) Overlaying NGS wiggle data is helpful in displaying differential expression
      and is simple to implement in RNASeqBrowser. (4) NGS data accumulates a lot of
      raw reads. Thus, RNASeqBrowser collapses exact duplicate reads to reduce
      visualization space. Normal PC's can show many windows of NGS individual raw
      reads without much delay. (5) Multiple popup windows of individual raw reads
      provide users with more viewing space. This avoids existing approaches (such as
      IGV) which squeeze all raw reads into one window. This will be helpful for
      visualizing multiple datasets simultaneously. RNASeqBrowser and its manual are
      freely available at
      http://www.australianprostatecentre.org/research/software/rnaseqbrowser or
      http://sourceforge.net/projects/rnaseqbrowser/.

PMID- 25766522
TI  - 'Wind-up' in Parkinson's disease: A functional magnetic resonance imaging study.
AB  - BACKGROUND: Parkinson's disease (PD) is a neurodegenerative disorder mainly
      marked by selective degeneration of dopaminergic neurons that leads to disabling
      motor and cognitive impairment. This condition is less widely appreciated as a
      disease associated with a substantial variety of pain syndromes, although the
      prevalence of pain is relatively high. Repeated painful stimulation of peripheral
      nerves can cause pain 'wind-up' if the frequency of the stimulation is adequate
      and specifically stimulates the afferent C-fibres. We presumed that in case of
      PD, pain or pain severeness might be frequently caused by the aggravation of the
      'wind-up' phenomenon due to any central or peripheral lesions or functional
      alterations. METHODS: To test for this hypothesis, we compared three groups
      (patients with left- and right-dominant PD and control subjects) using functional
      magnetic resonance imaging and thermally induced pain. RESULTS: Patient showed
      higher average 'wind-up' scores, compared to the healthy subjects, with lower
      values on the more affected sides compared to the less affected ones. In group
      level comparisons, patients had higher activation during 'wind-up' compared to
      control subjects in two main areas; these were the posterior division of
      cingulate gyrus and the precuneus cortex. In case of patients, further analyses
      showed that applied heat pain on the less affected side elicited higher
      activation in the supramarginal and postcentral gyri. CONCLUSIONS: These
      differences may arise from the deficiency in the efferent information, as well as
      the alterations in the central processing. It is highly likely that both
      processes contribute to this phenomenon simultaneously.

PMID- 25766523
TI  - Nitrous oxide related behavioral and histopathological changes may be related to
      oxidative stress.
AB  - Nitrous oxide (N2O) toxicity can result in myelin loss and hyperhomocysteinemia
      similar to cobalamin (Cbl) deficiency. Studies on N2O exposure can help in
      understanding the mechanism of demyelination. In view of paucity of studies on
      N2O toxicity in rats this study was undertaken. Six male wistar rats were exposed
      to 1.5L/min N2O with 1:1 O2 for 90 min daily for 1 month. After 1-month exposure
      blood homocysteine (HCY) and oxidative stress parameters glutathione (GSH) and
      total antioxidant capacity (TAC) were measured. Brain and spinal cord was
      subjected to histopathological examination. The neurobehavioral changes,
      oxidative stress parameters and histopathological changes were correlated with
      serum B12 and HCY level. After 1-month exposure, the rats appeared sluggish,
      lethargic and developed predominantly hind limb weakness for 1-1.5h. In the
      exposed group, the total distance traveled (2001.66 +/- 118.27 cm; p=0.037), time
      moving (80.16 +/- 5.7s; p=0.028), number of rearing (10.33 +/- 1.45; p=0.014) and
      grip strength (1042.40 +/- 51.3N; p=0.041) were significantly decreased whereas,
      resting time significantly increased (219.83 +/- 5.7s; p=0.030) compared to
      controls. Serum HCY level was significantly increased (20.56 +/- 1.296 MUm/ml;
      p=0.0007) in the exposed group. However, serum B12 and folic acid levels were not
      significantly different. GSH significantly decreased (2.21 +/- 0.60 mg/dl;
      p=0.018) along with TAC (0.76 +/- 0.16 Trolox_Eq_mmol/l; p=0.036). The
      histopathological studies revealed shrinkage and vacuolation of neurons in
      cerebral cortex, focal myelin loss, vacuolation in subcortical white matter and
      spinal cord. N2O exposure results in behavioral alterations,
      hyperhomocysteinemia, cortical and spinal cord demyelination which were
      associated with decrease GSH and TAC highlighting pathophysiological role of
      oxidative stress.

PMID- 25766524
TI  - SIRT1 suppresses doxorubicin-induced cardiotoxicity by regulating the oxidative
      stress and p38MAPK pathways.
AB  - BACKGROUND: SIRT1, which belongs to the Sirtuin family of NAD-dependent enzymes,
      plays diverse roles in aging, metabolism, and disease biology. It could regulate
      cell survival and has been shown to be a protective factor in heart function.
      Hence, we verified the mechanism by which SIRT1 regulates doxorubicin induced
      cardiomyocyte injury in vivo and in vitro. METHODS: We analyzed SIRT1 expression
      in doxorubicin-induced neonatal rat cardiomyocyte injury model and adult mouse
      heart failure model. SIRT1 was over-expressed in cultured neonatal rat
      cardiomyocyte by adenovirus mediated gene transfer. SIRT1 agonist resveratrol was
      used to treat the doxorubicin-induced heart failure mouse model.
      Echocardiography, reactive oxygen species (ROS) production, TUNEL, qRT-PCR, and
      Western blotting were performed to analyze cell survival, oxidative stress, and
      inflammatory signal pathways in cardiomyocytes. RESULTS: SIRT1 expression was
      down-regulated in doxorubicin induced cardiomocyte injury, accompanied by
      elevated oxidative stress and cell apoptosis. SIRT1 over-expression reduced
      doxorubicin induced cardiomyocyte apoptosis with the attenuated ROS production.
      SIRT1 also reduced cell apoptosis by inhibition of p38MAPK phosphorylation and
      caspase-3 activation. The SIRT1 agonist resveratrol was able to prevent
      doxorubicin-induced heart function loss. Moreover, the SIRT1 inhibitor
      niacinamide could reverse SIRT1's protective effect in cultured neonatal rat
      cardiomyocytes. CONCLUSIONS: These results support the role of SIRT1 as an
      important regulator of cardiomyocyte apoptosis during doxorubicin-induced heart
      injury, which may represent a potential therapeutic target for doxorubicin
      induced cardiomyopathy.

PMID- 25766525
TI  - Mitomycin C induces apoptosis in rheumatoid arthritis fibroblast-like
      synoviocytes via a mitochondrial-mediated pathway.
AB  - BACKGROUND/AIMS: Rheumatoid arthritis (RA) is a systemic chronic inflammatory
      disease characterised by prominent synoviocyte hyperplasia and a potential
      imbalance between the growth and death of fibroblast-like synoviocytes (FLS).
      Mitomycin C (MMC) has previously been demonstrated to inhibit fibroblast
      proliferation and to induce fibroblast apoptosis. However, the effects of MMC on
      the proliferation and apoptosis of human RA FLS and the potential mechanisms
      underlying its effects remain unknown. METHODS: Cell viability was determined
      using the Cell Counting Kit-8 assay. Apoptotic cell death was analysed via
      Annexin V-FITC/PI double staining and terminal deoxynucleotidyl transferase
      mediated dUTP-biotin nick-end labelling. The production of intracellular reactive
      oxygen species (ROS) was assessed via flow cytometry, and the changes in
      mitochondrial membrane potential (DeltaPsim) were visualized based on JC-1
      staining via fluorescence microscopy. The expression of apoptosis-related
      proteins was determined via Western blot. RESULTS: Treatment with MMC
      significantly reduced cell viability and induced apoptosis in RA FLS.
      Furthermore, MMC exposure was found to stimulate the production of ROS and to
      disrupt the DeltaPsim compared to the control treatment. Moreover, MMC increased
      the release of mitochondrial cytochrome c, the ratio of Bax/Bcl-2, the activation
      of caspase-9 and caspase-3, and the subsequent cleavage of poly(ADP-ribose)
      polymerase. CONCLUSION: Our findings suggest that MMC inhibits cell proliferation
      and induces apoptosis in RA FLS, and the mechanism underlying this MMC-induced
      apoptosis may involve a mitochondrial signalling pathway.

PMID- 25766526
TI  - Characterization and functions of vascular adventitial fibroblast subpopulations.
AB  - BACKGROUND: Adventitial fibroblasts have been shown to play an important role in
      vascular remodeling and contribute to neointimal formation in vascular diseases.
      However, little is known about adventitial fibroblast subpopulations. This study
      explored the process of isolating rat thoracic aorta adventitial fibroblast
      subpopulations and characterized their properties following stimulation with
      angiotensin II (ANG II), a critical factor involved in cardiovascular diseases
      such as hypertension. METHODS: Adventitial fibroblasts were isolated and cultured
      from rat aorta. Fibroblast subpopulations were individually expanded using
      cloning ring techniques. Cells were treated with ANG II (10 nM, 100 nM and 1 MUM)
      for 0.5, 1, 1.5, 3, 6, 12, or 24 h, and ANG II-induced proliferation and
      migration were measured by MTT assay and Transwell. Cells were treated with ANG
      II (100 nM) in the presence or absence of ANG II receptor antagonists (100 MUM),
      losartan (for AT1) and PD-123319 (for AT2). PreproET-1 mRNA and ET-1 were
      determined by RT-PCR and ELISA, respectively. Collagen type I was detected by
      western blotting. RESULTS: Two major fibroblast subpopulations were found in the
      adventitia, epithelioid-like cells and spindle-like cells; Although ANG II
      promotes the growth of both subpopulations, epithelioid-like cell proliferation
      shows dose-dependency on ANG II from 10 nM to 1 MUM, while proliferation of
      spindle-like cells reaches a peak value following 100 nM ANG II stimulation; ANG
      II stimulation enhanced epithelioid-like but not spindle-like cell migration; ANG
      II dose-dependently increased the expression of preproET-1 and collagen type I,
      and enhanced ET-1 secretion in epithelioid-like but not spindle-like cells,
      effects abolished by the AT1 receptor antagonist, but not with AT2 receptor
      antagonist. CONCLUSION: Adventitial fibroblasts are heterogeneous and epithelioid
      like subpopulations with high sensitivity to ANG II stimulation may be implicated
      in the pathophysiological mechanisms of vascular remodeling, reparative processes
      and cardiovascular diseases.

PMID- 25766527
TI  - Gas6 delays senescence in vascular smooth muscle cells through the PI3K/ Akt/FoxO
      signaling pathway.
AB  - BACKGROUND/AIMS: Growth arrest-specific protein 6 (Gas6) is a cytokine that can
      be synthesized by a variety of cell types and secreted into the extracellular
      matrix. Previous studies have confirmed that Gas6 is involved in certain
      pathophysiological processes of the cardiovascular system through binding to its
      receptor, Axl. In the present study, we investigated the role of Gas6 in cellular
      senescence and explored the mechanisms underlying its activity. METHODS: We used
      vascular smooth muscle cells (VSMCs) to create two cellular senescence models,
      one for replicative senescence (RS) and one for induced senescence (IS), to test
      the hypothesis that Gas6 delays senescence. RESULTS: Gas6-treated cells appear
      relatively younger compared with non-Gas6-treated cells. In particular, Gas6
      treated cells displayed decreased staining for SA-beta-Gal, fewer G1 phase cells,
      and decreased levels of p16(INK4a) and p21(Cip1) expression; conversely, Gas6
      treated cells displayed more S phase cells and significantly increased
      proliferation indexes. Furthermore, in both the IS and RS models with Gas6
      treatment, the levels of PI3K, p-Akt, and p-FoxO3a decreased following Axl
      inhibition by R428; similarly, the levels of p-Akt and p-FoxO3a also decreased
      following PI3K inhibition by LY294002. CONCLUSION: Gas6/Axl signaling is
      essential for delaying the cellular senescence process regulated by the
      PI3K/Akt/FoxO signaling pathway.

PMID- 25766528
TI  - MiR-940 inhibited pancreatic ductal adenocarcinoma growth by targeting MyD88.
AB  - BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is an almost universally
      lethal disease. Deregulation or dysfunction of miRNAs contribute to cancer
      development. The role of miR-940 in PDAC remains unclear. METHODS: The level of
      miR-940 in PDAC tissues and cell lines was measured by qRT-PCR. MiR-940 was over
      expressed by miRNAs mimics transfection and reduced by miRNAs antisense
      oligonucleotides (ASO) transfection. Cell proliferation was analyzed by MTT assay
      and cell apoptosis was evaluated by FACS analysis. Targeted genes were predicted
      by a bioinformatics algorithm and confirmed by a dual luciferase reporter assay.
      Myeloid differentiation primary response gene (88) (MyD88) protein level was
      assayed by immunohistochemistry and Western blot analysis. RESULTS: Low miR-940
      level and high MyD88 protein level in PDAC tissues were both correlated with low
      survival rate. Up-regulation of miR-940 inhibited PDAC cell lines growth while
      down-regulation induced cell growth. The 3' UTR of MyD88 was targeted by miR-940.
      CONCLUSIONS: Low level of miR-940 and high level of MyD88 in PDAC promoted PDAC
      cells growth which might be related to the low survival rate of PDAC patients.
      MiR-940 exerted its effect by targeting MyD88.

PMID- 25766529
TI  - Expression and potential role of microRNA-29b in mouse early embryo development.
AB  - BACKGROUND/AIMS: MicroRNA-29b (miR29b) has been previously identified in early
      mouse embryos through miRNA microarray analysis. Recent research has indicated
      that miR29b participates in DNA methylation by regulating DNA methyltransferase
      3a/3b (Dnmt3a/3b) expression. However, the expression pattern and biological
      function of miR29b in mouse preimplantation embryonic development remain unknown.
      METHODS: In this study, we examined the expression patterns of miR29b and
      Dnmt3a/3b in mouse early embryos at different developmental stages. Subsequently,
      expression and localization of DNMT3A/3B protein was analyzed in mouse early
      embryos by immunofluorescence staining. The biological function of miR29b in
      mouse early embryos was analyzed by microinjection of commercially available
      miRNA-specific inhibitors and mimics. RESULTS: Our data showed that Dnmt3a/3b
      mRNA expression is negatively regulated by miR29b in mouse early embryos.
      Immunofluorescence analysis revealed that DNMT3A/3B protein expression is
      predominantly localized within the nucleoplasm of embryos. Alterations to the
      activity of miR29b could change the DNA methylation levels in mouse
      preimplantation embryos and lead to a developmental blockade, from the morula to
      the blastocyst stage. CONCLUSION: These results indicated a role for the miR29b
      Dnmt3a/3b-DNA methylation axis in mouse early embryonic development, and we
      provide evidence that miR29b is indispensable for mouse early embryonic
      development. This study contributes to a preliminary understanding of the role of
      miR29b during mouse embryonic development.

PMID- 25766530
TI  - Prognostic role of tissue and circulating microRNA-200c in malignant tumors: a
      systematic review and meta-analysis.
AB  - BACKGROUND: Recently, many studies have shown that microRNAs (miRNA) exhibit
      altered expression in various cancers and may serve as prognostic biomarkers. We
      performed a systematic review and meta-analysis to evaluate the prognostic role
      of miR-200c expression in different cancers. METHODS: Studies were recruited by
      searching PubMed, Embase and the Cochrane Library (last search update was May
      2014) and assessed by further quality evaluation. RESULTS: A total of 25 studies
      dealing with various carcinomas were identified for systematic review. Among
      them, 18 studies were ultimately included in the meta-analysis. Our results
      indicated that the expression of tissue miR-200c was not associated with OS and
      PFS in various carcinomas; however, downregulation of tissue miR-200c did predict
      poor OS of patients with stage I disease (HR=0.41, 95% CI 0.25-0.68, P=0.001).
      Furthermore, overexpression of blood miR-200c was significantly related to poor
      OS and PFS (HR=3.07 95% CI 1.58-5.96 P=0.001, HR=2.26 95% CI 1.66-3.08 P<0.001,
      respectively), especially in patients with advanced disease. CONCLUSION: This
      systematic review and meta-analysis clarified that low expression of miR-200c in
      primary tissue was significantly associated with poor survival in cancer patients
      at early stage, whereas a high level of blood miR-200c predicted poor prognosis
      in patients with advanced tumors.

PMID- 25766531
TI  - Nitro-oleic acid attenuates OGD/R-triggered apoptosis in renal tubular cells via
      inhibition of Bax mitochondrial translocation in a PPAR-gamma-dependent manner.
AB  - BACKGROUND: Nitroalkene derivatives of oleic acid (OA-NO2) serve as high-affinity
      ligand for PPAR-gamma, which regulates apoptosis, oxidation and inflammation and
      plays a central role in ischemia-reperfusion injury. In the present study, we
      elucidated the protective mechanisms of OA-NO2 against renal ischemia-reperfusion
      injury. METHODS: HK-2 cells were subjected to oxygen and glucose deprivation
      followed by re-oxygenation (OGD/R) to mimic renal ischemia-reperfusion injury.
      Cell apoptosis was analyzed by flow cytometry. Bax mitochondrial translocation,
      cytochrome c and apoptosis-inducing factor (AIF) cytosolic leakage and Akt/Gsk
      3beta phosphorylation were evaluated by Western blotting. Bax activation was
      visualized by immunocytochemistry. GW9662 and siRNA transfection were employed to
      examine the involvement of PPAR-gamma. RESULTS: OGD/R injury promoted
      mitochondrial translocation and activation of Bax, leakage of cytochrome c and
      AIF, subsequent caspase-3 activation, and eventually cell apoptosis. Pre
      incubation with OA-NO2 (1.25 uM, 45min) inhibited Bax activation and blocked
      apoptotic cascade, while the protective effects were negated by GW9662 or PPAR
      gamma siRNA. Moreover, OA-NO2 restored Akt and Gsk 3beta phosphorylation in a
      PPAR-gamma-dependent way. CONCLUSION: These findings suggest that OA-NO2
      attenuates OGD/R-induced apoptosis by inhibiting Bax translocation and activation
      and the subsequent mitochondria-dependent apoptotic cascade in a PPAR-gamma
      dependent manner.

PMID- 25766532
TI  - Mesenchymal stem cells promote cardiac muscle repair via enhanced
      neovascularization.
AB  - BACKGROUND/AIMS: Transplantation of bone-marrow derived stem/progenitor cells has
      an established therapeutic effect on cardiac muscle repair after injury. However,
      the exact mechanism that underlies this phenomenon is not completely understood.
      METHODS: Here we transplanted mesenchymal stem cells (MSCs), a major population
      from the bone-marrow derived stem/progenitor cells, and studied its effects on
      cardiac muscle repair after injury. RESULTS: MSCs transplantation significantly
      improved cardiac muscle repair after injury. The grafted MSCs did not
      significantly differentiate into cardiac muscle cells themselves, but appeared to
      induce neovascularization in the injured heart. In a loss-of-function experiment,
      we further show that production and secretion of placental growth factor, but not
      vascular endothelial growth factor A in MSCs, were essential for the MSCs-induced
      neovasularization after cardiac muscle injury to facilitate cardiac muscle
      repair. CONCLUSION: Our study thus sheds light on an undescribed role of
      placental growth factor in cardiac muscle regeneration.

PMID- 25766533
TI  - Induction of haemeoxygenase-1 improves FFA-induced endothelial dysfunction in rat
      aorta.
AB  - BACKGROUND: The induction of haemeoxygenase-1 (HO-1) exerts beneficial effects in
      the setting of endothelial dysfunction in obesity. High free fatty acid (FFA)
      levels are a common feature of obesity and are the primary cause of endothelial
      dysfunction. The objective of our study was to explore the effects of HO-1
      induction on FFA-induced endothelial dysfunction in rats. METHODS: Rats received
      FFA treatment with either cobalt protoporphyrin (CoPP) to induce HO-1 or stannous
      protoporphyrin (SnPP) to inhibit HO-1. Endothelial function was determined by
      measuring endothelium-dependent vasodilatation (EDV). Nitric oxide (NO)
      production, superoxide production and nuclear factor (NF)-kappaB expression in
      the aorta were each determined. The levels of adenosine monophosphate (AMP)
      activated kinase (AMPK) and endothelial nitric oxide synthase (eNOS) expression
      in endothelial cells were determined via Western blotting. RESULTS: Induction of
      HO-1 by CoPP decreased circulating FFA, high-sensitivity C-reactive protein and
      malondialdehyde levels and increased serum adiponectin and glutathione levels
      compared with the FFA group (P<0.05). High FFA levels resulted in EDV impairment,
      which was improved by HO-1 induction (P<0.05). Induction of HO-1 increased NO
      levels and reduced aortic superoxide production and NF-kappaB expression compared
      with the FFA group. The FFA group exhibited decreased AMPK expression and eNOS
      phosphorylation, both of which were enhanced via HO-1 induction (P<0.05). The
      beneficial effects of CoPP on EDV were partially attenuated in vitro in the
      presence of inhibitors of AMPK, phosphatidylinositol 3-kinase (PI3K), and eNOS.
      CONCLUSIONS: HO-1 induction with CoPP improves FFA-induced endothelial
      dysfunction in the rat aorta. The protective mechanism appears to be related to
      the activation of the AMPK-PI3K-eNOS pathway as a result of increased adiponectin
      levels as well as decreased inflammation and oxidative stress.

PMID- 25766535
TI  - Erratum.

PMID- 25766534
TI  - Increased oxidative stress and mitochondrial dysfunction in zucker diabetic rat
      liver and brain.
AB  - BACKGROUND/AIMS: The Zucker diabetic fatty (ZDF, FA/FA) rat is a genetic model of
      type 2 diabetes, characterized by insulin resistance with progressive metabolic
      syndrome. We have previously demonstrated mitochondrial dysfunction and oxidative
      stress in the heart, kidneys and pancreas of ZDF rats. However, the precise
      molecular mechanism of disease progression is not clear. Our aim in the present
      study was to investigate oxidative stress and mitochondrial dysfunction in the
      liver and brain of ZDF rats. METHODS: In this study, we have measured
      mitochondrial oxidative stress, bioenergetics and redox homeostasis in the liver
      and brain of ZDF rats. RESULTS: Our results showed increased reactive oxygen
      species (ROS) production in the ZDF rat brain compared to the liver, while nitric
      oxide (NO) production was markedly increased both in the brain and liver. High
      levels of lipid and protein peroxidation were also observed in these tissues.
      Glutathione metabolism and mitochondrial respiratory functions were adversely
      affected in ZDF rats when compared to Zucker lean (ZL, +/FA) control rats.
      Reduced ATP synthesis was also observed in the liver and brain of ZDF rats.
      Western blot analysis confirmed altered expression of cytochrome P450 2E1, iNOS,
      p-JNK, and IkappaB-alpha confirming an increase in oxidative and metabolic stress
      in ZDF rat tissues. CONCLUSIONS: Our data shows that, like other tissues, ZDF rat
      liver and brain develop complications associated with redox homeostasis and
      mitochondrial dysfunction. These results, thus, might have implications in
      understanding the etiology and pathophysiology of diabesity which in turn, would
      help in managing the disease associated complications.

PMID- 25766537
TI  - A strong field and a deserving winner.

PMID- 25766536
TI  - Risk of Adverse Pregnancy Outcomes in Women with CKD.
AB  - CKD is increasingly prevalent in pregnancy. In the Torino-Cagliari Observational
      Study (TOCOS), we assessed whether the risk for adverse pregnancy outcomes is
      associated with CKD by comparing pregnancy outcomes of 504 pregnancies in women
      with CKD to outcomes of 836 low-risk pregnancies in women without CKD. The
      presence of hypertension, proteinuria (>1 g/d), systemic disease, and CKD stage
      (at referral) were assessed at baseline. The following outcomes were studied:
      cesarean section, preterm delivery, and early preterm delivery; small for
      gestational age (SGA); need for neonatal intensive care unit (NICU); new onset of
      hypertension; new onset/doubling of proteinuria; CKD stage shift; "general"
      combined outcome (preterm delivery, NICU, SGA); and "severe" combined outcome
      (early preterm delivery, NICU, SGA). The risk for adverse outcomes increased
      across stages (for stage 1 versus stages 4-5: "general" combined outcome, 34.1%
      versus 90.0%; "severe" combined outcome, 21.4% versus 80.0%; P<0.001). In women
      with stage 1 CKD, preterm delivery was associated with baseline hypertension
      (odds ratio [OR], 3.42; 95% confidence interval [95% CI], 1.87 to 6.21), systemic
      disease (OR, 3.13; 95% CI, 1.51 to 6.50), and proteinuria (OR, 3.69; 95% CI, 1.63
      to 8.36). However, stage 1 CKD remained associated with adverse pregnancy
      outcomes (general combined outcome) in women without baseline hypertension,
      proteinuria, or systemic disease (OR, 1.88; 95% CI, 1.27 to 2.79). The risk of
      intrauterine death did not differ between patients and controls. Findings from
      this prospective study suggest a "baseline risk" for adverse pregnancy-related
      outcomes linked to CKD.

PMID- 25766538
TI  - Unravelling the 'tangled web': chemotherapy for tuberculosis in Britain, 1940-70
      the William Bynum prize essay.
AB  - The introduction and assimilation of chemotherapy to treat pulmonary tuberculosis
      (TB) during the mid-twentieth century appears at first sight to be a success
      story dominated by the use of streptomycin in a series of randomised clinical
      trials run under the auspices of the Medical Research Council (MRC). However,
      what this standard rhetoric overlooks is the complexity of TB chemotherapy, and
      the relationship between this and two other ways of treating the disease, bed
      rest and thoracic surgery. During the late 1940s and 1950s, these three treatment
      strands overlapped one another, and determining best practice from a plethora of
      prescribing choices was a difficult task. This article focuses on the clinical
      decision-making underpinning the evolution of successful treatment for TB using
      drugs alone. Fears over the risk of streptomycin-resistant organisms entering the
      community meant that, initially, the clinical application of streptomycin was
      limited. Combining it with other drugs lessened this risk, but even so the
      potential of chemotherapy as a curative option for TB was not immediately
      apparent. The MRC ran a series of clinical trials in the post-war period but not
      all of their recommendations were adopted by clinicians in the field. Rather, a
      range of different determinants, including the timing of trials, the time taken
      for results to emerge, and whether these results 'fitted' with individual
      experience all influenced the translation of trial results into clinical
      practice. 

PMID- 25766539
TI  - Nurturing the citizens of the future: milk stations and child nutrition in Puerto
      Rico, 1929-60.
AB  - Between the 1930s and 1960s Puerto Rico was transformed from a marginal United
      States territory into an industrialised 'showcase of development'. This article
      investigates the organisation of milk station programmes on the island during
      this crucial period and how these reflected the circulation of child welfare
      knowledge, nutrition expertise and public health practices. During the
      Depression, these perspectives fostered a recast of the eugenic regeneration
      ideologies motivating medical assessments of and sanitary interventions with
      Puerto Rico's rural poor since the nineteenth century. Innovations in nutrition
      knowledge and an emerging rural hygiene movement highlighted the negative health
      effects of the island's monocrops economy. In this context, the nourishment of
      children's bodies assumed symbolic and instrumental significance for the
      reconfiguration of colonial and developmental models promoted by the new Popular
      Democratic Party (PPD). The experience of public health professionals in relief
      work during the 1930s contributed to the articulation of food and nutrition as
      key elements of this party's populist discourse. Programmes like milk stations
      became part of strategies to rear and manage the labour force needed in the
      industrial development model promoted by the PPD. From the perspective of poor
      Puerto Ricans, however, they were part of the materialisation of its promise of
      social justice for the poorer classes. 

PMID- 25766540
TI  - Venereology at the polyclinic: postgraduate medical education among general
      practitioners in England, 1899-1914.
AB  - In 1899 the British Medical Journal enthusiastically announced that a new
      postgraduate teaching college was to open in London. The aim of the Medical
      Graduates' College and Polyclinic (MGC) was to provide continuing education to
      general practitioners. It drew upon emerging specialisms and in so doing built
      upon the generalist training received at an undergraduate level. Courses were
      intended to refresh knowledge and to introduce general practitioners to new
      knowledge claims and clinical practices. The establishment of postgraduate
      institutions such as the MGC marked an important stage in the development of
      medical education in England. Yet these institutions, and the emergence of
      postgraduate medical education more broadly, have been largely overlooked by
      historians. Moreover the history of venereological training among medical
      undergraduates and postgraduates alike has been overlooked. The study of such
      special subjects characterised postgraduate study. This article examines the
      dissemination of venereological knowledge among subscribers to MGC as an
      important case study for the development of institutionalised postgraduate
      medical education in England at the turn of the twentieth century. 

PMID- 25766541
TI  - Cullen, a cautionary tale.
AB  - Some ideas return after the briefest of exiles: reductionism is back in vogue.
      Existential questions - about who we are, about our origins and future, about
      what is valuable - no longer require difficult soul searching, especially when
      straightforward answers are expected from the neurosciences. History is being
      rewritten with the brain as its centrepiece; the search for great men and big
      ideas of the past begins again. William Cullen (1710-90), whose work on neurosis
      was once part of the history of psychoanalysis, is now well placed to become part
      of such a neuro-history. This article attempts to subvert this process, by
      rebuilding the original meaning of neurosis through Cullen's physiological and
      medical works, in comparison with his predecessor, Robert Whytt (1714-66), and
      illustrating this meaning using one particular neurosis: hypochondriasis. The
      result is a more complicated version of neurosis which, importantly, carries
      significant insights into the nature and practice of medicine. Moreover, this
      article examines how Cullen's standing fell in the 1820s as British physicians
      and surgeons turned to an idea which promised to reform medicine: pathological
      anatomy. When these hopes faded, Cullen became a figure obsessed with the nerves.
      This image has survived to the present, a blank canvas onto which any theory can
      be projected. It also values precisely what Cullen warned against: simplistic
      explanations of the body and disease, and unthinking confidence in the next big
      idea or silver bullet. Neurosis was not simply a nervous ailment, but it is a
      warning against reductionism in history making. 

PMID- 25766542
TI  - Forgotten dreams: recalling the patient in British psychotherapy, 1945-60.
AB  - The forgotten dream proved central to the early development of Sigmund Freud's
      psychoanalytic technique in The Interpretation of Dreams (1900). However, little
      attention has been paid to the shifting uses of forgotten dreams within
      psychotherapeutic practice over the course of the twentieth century. This paper
      argues that post-war psychotherapists in London, both Jungian and Freudian,
      developed a range of subtly different approaches to dealing with their patients'
      forgotten dreams. Theoretical commitments and institutional cultures shaped the
      work of practitioners including Donald Winnicott, Melanie Klein, Anna Freud, and
      Edward Griffith. By drawing on diaries and case notes, this paper also identifies
      the active role played by patients in negotiating the mechanics of therapy, and
      the appropriate response to a forgotten dream. This suggests a broader need for a
      detailed social history of post-Freudian psychotherapeutic technique, one that
      recognises the demands of both patients and practitioners. 

PMID- 25766543
TI  - Pain and Surgery in England, circa 1620-circa 1740.
AB  - The scholarship on the discussion and role of pain in early modern English
      surgery is limited. Scholars have given little consideration to how surgeons
      described and comprehended pain in their patients' bodies in early modern
      England, including how these understandings connected to notions of the humours,
      nerves and sex difference. This article focuses on the attention that surgeons
      paid to pain in their published and manuscript casebooks and manuals available in
      English, circa 1620-circa 1740. Pain was an important component of surgery in
      early modern England, influencing diagnosis, treatment and technique. Surgeons
      portrayed a complex and multi-dimensional understanding of their patients' bodies
      in pain, which was further connected to their portrayals of their professional
      ability. 

PMID- 25766544
TI  - Greek manuscripts at the Wellcome Library in London: a descriptive catalogue.
AB  - This article presents a new, detailed catalogue of the Greek manuscripts at the
      Wellcome Library in London. It consists of an introduction to the history of the
      collection and its scholarly importance, followed by separate entries for each
      manuscript. Each entry identifies the text(s) found in the respective manuscript 
      including reference to existing printed edition(s) of such texts - and gives a
      physical description of the codex, details on its provenance and bibliographical
      references. 

PMID- 25766560
TI  - Enterovirus D68: a new threat to hematology patients?

PMID- 25766561
TI  - Thucydides and longer-lived plasma cells.

PMID- 25766562
TI  - Heat-shock proteins: a c-Myc lymphoma target?

PMID- 25766563
TI  - A "RANning" leap with "XPOrt" into TKI resistance.

PMID- 25766564
TI  - The end of the line for neutrophils.

PMID- 25766565
TI  - C-reactive protein boosts antibody-mediated platelet destruction.

PMID- 25766566
TI  - CD56(dim)CD16- NK cell phenotype can be induced by cryopreservation.

PMID- 25766567
TI  - Liberation of ATP secondary to hemolysis is not mutually exclusive of regulated
      export.

PMID- 25766568
TI  - Response: Hemolysis is a primary and physiologically relevant ATP release
      mechanism in human erythrocytes.

PMID- 25766569
TI  - [The French society of medical mycology in 2015].

PMID- 25766570
TI  - Prognostic Factors of Patients with Gastric Gastrointestinal Stromal Tumor after
      Curative Resection: A Retrospective Analysis of 406 Consecutive Cases in a
      Multicenter Study.
AB  - BACKGROUND/PURPOSE: Gastric gastrointestinal stromal tumors (GISTs) have a highly
      variable clinical course, and recurrent disease sometimes develops despite
      curative surgery. This study was undertaken to investigate the surgical role in
      treating gastric GISTs and evaluate the clinicopathological features of a large
      series of patients who underwent curative resection for gastric GISTs to clarify
      which features were independent prognostic factors. METHODS: The
      clinicopathological data of 406 patients with gastric GISTs who underwent
      curative resection at 4 university hospitals in Daegu, South Korea, from March
      1998 to March 2012 were reviewed. All cases were confirmed as gastric GISTs by
      immunohistochemical staining, in which CD117 or CD34 was positive. Clinical
      follow-up was performed periodically, and disease-free survival rates were
      retrospectively investigated using the medical records. RESULTS: The mean follow
      up period was 42.9 months (range: 2-166). There were 11 recurrent patients
      (2.7%). Due to the small number of recurrences, age, sex and location were
      controlled using propensity score matching before performing any statistical
      analysis. Tumor size, mitotic count, NIH classification, and cellularity were
      judged to be independent prognostic factors for recurrence by univariate
      analysis. In a multivariate analysis, tumor size and mitotic count were
      significantly and independently related to recurrence, and tumor size was
      determined to be the most important prognostic factor for recurrence after
      curative resection (hazard ratio: 1.204; p < 0.01). CONCLUSIONS: The results of
      this multicenter study demonstrate that disease-free survival rates are good.
      Tumor size was disclosed as the most important factor for recurrence in gastric
      GIST patients who underwent radical resection.

PMID- 25766571
TI  - Effects of ultrasound frequency and tissue stiffness on the histotripsy intrinsic
      threshold for cavitation.
AB  - Histotripsy is an ultrasound ablation method that depends on the initiation of a
      cavitation bubble cloud to fractionate soft tissue. Previous work has indicated
      that a cavitation cloud can be formed by a single pulse with one high-amplitude
      negative cycle, when the negative pressure amplitude directly exceeds a pressure
      threshold intrinsic to the medium. We hypothesize that the intrinsic threshold in
      water-based tissues is determined by the properties of the water inside the
      tissue, and changes in tissue stiffness or ultrasound frequency will have a
      minimal impact on the histotripsy intrinsic threshold. To test this hypothesis,
      the histotripsy intrinsic threshold was investigated both experimentally and
      theoretically. The probability of cavitation was measured by subjecting tissue
      phantoms with adjustable mechanical properties and ex vivo tissues to a
      histotripsy pulse of 1-2 cycles produced by 345-kHz, 500-kHz, 1.5-MHz and 3-MHz
      histotripsy transducers. Cavitation was detected and characterized by passive
      cavitation detection and high-speed photography, from which the probability of
      cavitation was measured versus pressure amplitude. The results revealed that the
      intrinsic threshold (the negative pressure at which probability = 0.5) is
      independent of stiffness for Young's moduli (E) <1 MPa, with only a small
      increase (~2-3 MPa) in the intrinsic threshold for tendon (E = 380 MPa).
      Additionally, results for all samples revealed only a small increase of ~2-3 MPa
      when the frequency was increased from 345 kHz to 3 MHz. The intrinsic threshold
      was measured to be between 24.7 and 30.6 MPa for all samples and frequencies
      tested in this study. Overall, the results of this study indicate that the
      intrinsic threshold to initiate a histotripsy bubble cloud is not significantly
      affected by tissue stiffness or ultrasound frequency in the hundreds of kilohertz
      to megahertz range.

PMID- 25766572
TI  - On the relationship between microbubble fragmentation, deflation and broadband
      superharmonic signal production.
AB  - Acoustic angiography imaging of microbubble contrast agents uses the
      superharmonic energy produced from excited microbubbles and enables high
      contrast, high-resolution imaging. However, the exact mechanism by which
      broadband harmonic energy is produced is not fully understood. To elucidate the
      role of microbubble shell fragmentation in superharmonic signal production,
      simultaneous optical and acoustic measurements were performed on individual
      microbubbles at transmit frequencies from 1.75 to 3.75 MHz and pressures near the
      shell fragmentation threshold for microbubbles of varying diameter. High
      amplitude, broadband superharmonic signals were produced with shell
      fragmentation, whereas weaker signals (approximately 25% of peak amplitude) were
      observed in the presence of shrinking bubbles. Furthermore, when populations of
      stationary microbubbles were imaged with a dual-frequency ultrasound imaging
      system, a sharper decline in image intensity with respect to frame number was
      observed for 1-MUm bubbles than for 4-MUm bubbles. Finally, in a study of two
      rodents, increasing frame rate from 4 to 7 Hz resulted in decreases in mean
      steady-state image intensity of 27% at 1000 kPa and 29% at 1300 kPa. Although the
      existence of superharmonic signals when bubbles shrink has the potential to
      prolong the imaging efficacy of microbubbles, parameters such as frame rate and
      peak pressure must be balanced with expected re-perfusion rate to maintain
      adequate contrast during in vivo imaging. 

PMID- 25766573
TI  - Tinea nigra showing a parallel ridge pattern on dermoscopy.
AB  - An 18-year-old healthy female student noticed a brown macule measuring 21 mm in
      diameter on the left palm and visited our clinic concerned about a cancerous
      mole. Dermoscopic examination revealed a brown, fine-dotted and granule-like
      structure overlapping an amorphous light brown macule. However, unlike previous
      cases, analysis of the high dynamic range-converted image revealed the parallel
      ridge pattern frequently observed in malignant melanomas. Brown mycelia were
      detected on direct microscopic examination; black colonies were isolated on
      fungal culture and the fungus was identified as Hortaea werneckii. The lesion was
      treated with topical ketoconazole cream, and it diminished 1 month later. 

PMID- 25766574
TI  - Synthesis of novel tryptamine-based macrocycles using an Ugi 4-CR/microwave
      assisted click-cycloaddition reaction protocol.
AB  - A practical synthesis of novel tryptamine-based macrocycles using an Ugi 4
      CR/click-cycloaddition sequential reaction protocol is described. The main
      features of the macrocyclic scaffolds are a peptoid moiety, a 1,3-substituted
      indole nucleus, and a triazole ring. 

PMID- 25766575
TI  - Role of amyloid from a multiple sclerosis perspective: a literature review.
AB  - The traditional concept of multiple sclerosis (MS), that it is primarily a white
      matter inflammatory disease, has changed a great deal. Thanks to the recent
      development witnessed in MS research, a whole new idea has emerged that MS is a
      neurodegenerative disease, and neurodegeneration occurs rather earlier in the
      pathological process. This has also led to the foundation of the hypothesis that
      two fundamentally different diseases, Alzheimer's disease (AD) and MS, may share
      a common mechanism of neurodegeneration. Conventionally, amyloid is thought to be
      a consequence of protein misfolding and aggregation and is most notorious for its
      association with debilitating and chronic human diseases. Amyloid is implicated
      to be related with the deterioration and progression of AD. The finding of
      amyloid precursor protein expression in axons around the plaque in MS, as well as
      the correlation of amyloid-beta (Abeta) with different stages of MS, has clearly
      indicated that amyloid plays some kind of key role in MS disease pathogenesis.
      Excitingly, a paradoxical phenomenon of Abeta has also been observed in several
      studies recently. It has been shown that amyloid might actually be helping in
      ameliorating the inflammatory effect in diseases like AD and MS. Amyloid imaging
      allows earlier diagnosis of MS by taking advantage of the relation of amyloid
      with MS. This will have a big impact on patient diagnosis and management. In this
      review I have included the findings of research studies dating from several years
      back to the most recent ones. Through this review I have tried to show the
      critical role of amyloid in MS and the importance of investigating through PET
      imaging. 

PMID- 25766577
TI  - Choice of PCR microtube can impact on the success of long-range PCRs.
AB  - We compared four brands of microtubes with respect to their suitability for long
      range polymerase chain reactions (PCRs). One of the four brands was found to have
      an inhibitory effect, decreasing PCR yields. The effect was universal across
      different PCR or enzyme systems. Increased ultraviolet absorbance suggests
      leaching of unknown chemical species into PCR mixtures. However, this could not
      be confirmed by high-performance liquid chromatography-mass spectrometry
      analysis. Nevertheless, our article demonstrates a clear impact of the choice of
      microtubes on long-range PCR success. Due consideration should be given to the
      PCR microtubes when determining optimal reaction conditions for long-range PCR. 

PMID- 25766578
TI  - A targeted metabolomics approach toward understanding metabolic variations in
      rice under pesticide stress.
AB  - Diazinon insecticide is widely applied throughout rice (Oryza sativa L.) fields
      in Iran. However, concerns are now being raised about its potential adverse
      impacts on rice fields. In this study, a time-course metabolic change in rice
      plants was investigated after diazinon treatment using gas chromatography-mass
      spectrometry (GC-MS), and subsequently the statistical strategy of random forest
      (RF) was performed in order to find the stress-associated effects. According to
      the results, a wide range of metabolites were dynamically varied as a result of
      the plant response to diazinon such as biosynthesis and metabolism of sugars,
      amino acids, organic acids, and phenylpropanoids, all correlating with the
      exposure time. Plant response was involved in multiple metabolic pathways, most
      of which were correlated with the exposure time. In this study, RF was explored
      as a potential multivariate method for GC-MS analysis of metabolomics data of
      rice (O. sativa L.) plants under diazinon stress; more than 31 metabolites were
      quantitatively determined, and time-course metabolic response of the plant during
      different days after treatment was measured. Results demonstrated RF as a
      potential multivariate method for GC-MS analysis of changes in plant metabolome
      under insecticide stress. 

PMID- 25766576
TI  - MTRAQ-based quantitative analysis combined with peptide fractionation based on
      cysteinyl peptide enrichment.
AB  - In the present study, the fractionation scheme for cysteinyl peptide enrichment
      (CPE) was combined with the mass differential tags for relative and absolute
      quantification (mTRAQ) method to reduce sample complexity and increase proteome
      coverage. Cysteine residues of the proteins were first alkylated using iodoacetyl
      PEG2-biotin instead of other conventional alkylating agents such as
      iodoacetamide. After trypsin digestion, amine groups were labeled with mTRAQ, and
      these labeled peptides were fractionated according to the presence or absence of
      cysteine residues using avidin-biotin affinity chromatography. With these
      approaches, we were able to divide the peptides into the two fractions with more
      than 90% fractionation efficiency for standard protein and MCF7 cell lysate. When
      the fractionation strategy was applied to colorectal cancer tissue samples, we
      were able to obtain quantitative information that was consistent with the
      previous study based on mTRAQ quantification, implying that the cysteine-based
      fractionation method does not affect mTRAQ quantification. We expect that the
      mTRAQ-based quantitative analysis combined with peptide fractionation through the
      CPE strategy would allow for deep-down analysis of proteome samples and
      ultimately for increasing proteome coverage with simultaneous quantification for
      biomarker discovery. 

PMID- 25766579
TI  - Detection of carcinoembryonic antigen using single-domain or full-size antibodies
      stained with quantum dot conjugates.
AB  - Compact single-domain antibodies (sdAbs) are nearly 13 times smaller than full
      size monoclonal antibodies (mAbs) and have a number of advantages for
      biotechnological applications, such as small size, high specificity, solubility,
      stability, and great refolding capacity. Carcinoembryonic antigen (CEA) is a
      tumor-associated glycoprotein expressed in a variety of cancers. Detection of CEA
      on the tumor cell surface may be carried out using anti-CEA antibodies and
      conventional fluorescent dyes. Semiconductor quantum dots (QDs) are brighter and
      more photostable than organic dyes; they provide the possibility for labeling of
      different recognition molecules with QDs of different colors but excitable with
      the same wavelength of excitation. In this study, the abilities for specific
      detection of CEA expressed by tumor cells with anti-CEA sdAbs biotinylated in
      vitro and in vivo, as well as with anti-CEA mAbs biotinylated in vitro, were
      compared using flow cytometry and the conjugates of streptavidin with QDs (SA
      QDs). The results demonstrated that either in vitro or in vivo biotinylated anti
      CEA sdAbs are more sensitive for cell staining compared to biotinylated anti-CEA
      mAbs. The data also show that simultaneous use of biotinylated sdAbs with highly
      fluorescent SA-QDs can considerably improve the sensitivity of detection of CEA
      on tumor cell surfaces.

PMID- 25766580
TI  - Dividing a complex reaction involving a hypervalent iodine reagent into three
      limiting mechanisms by ab initio molecular dynamics.
AB  - The electrophilic N-trifluoromethylation of MeCN with a hypervalent iodine
      reagent to form a nitrilium ion, that is rapidly trapped by an azole nucleophile,
      is thought to occur via reductive elimination (RE). A recent study showed that,
      depending on the solvent representation, the S(N)2 is favoured to a different
      extent over the RE. However, there is a discriminative solvent effect present,
      which calls for a statistical mechanics approach to fully account for the
      entropic contributions. In this study, we perform metadynamic simulations for two
      trifluoromethylation reactions (with N- and S-nucleophiles), showing that the RE
      mechanism is always favoured in MeCN solution. These computations also indicate
      that a radical mechanism (single electron transfer) may play an important role.
      The computational protocol based on accelerated molecular dynamics for the
      exploration of the free energy surface is transferable and will be applied to
      similar reactions to investigate other electrophiles on the reagent. Based on the
      activation parameters determined, this approach also gives insight into the
      mechanistic details of the trifluoromethylation and shows that these commonly
      known mechanisms mark the limits within which the reaction proceeds.

PMID- 25766581
TI  - Photoinduced formation of an azobenzene-based CD-active supramolecular cyclic
      dimer.
AB  - A series of new photo-responsive amino acid-derived azobenzenedicarboxylic acid
      derivatives (S)-1 a-e were synthesized. Compound (S)-1 a in the trans form
      exhibited no circular dichroism (CD) signal in DMF under ambient conditions,
      whereas intense Cotton effects were observed upon UV irradiation, indicating the
      formation of a chiral supramolecular structure in the cis form. The CD signals
      disappeared when trifluoroacetic acid (TFA) was added to the solution. The ester
      counterpart [(S)-1 a'] showed no CD signal. Hydrogen bonding between the carboxy
      groups seemed necessary for constructing the supramolecular structure. The
      kinetic studies of cis to trans isomerization of (S)-1 a demonstrated that the
      formation of a chiral supramolecule enhances the stability of the cis-azobenzene
      structure. The ESI mass spectrum of stilbenedicarboxylic acid (S)-4, an analogue
      of (S)-1 b, confirmed the formation of a dimer. A theoretical CD study revealed
      that (S)-1 a in the cis form should be present as a cyclic chiral dimer. 

PMID- 25766582
TI  - IPred - integrating ab initio and evidence based gene predictions to improve
      prediction accuracy.
AB  - BACKGROUND: Gene prediction is a challenging but crucial part in most genome
      analysis pipelines. Various methods have evolved that predict genes ab initio on
      reference sequences or evidence based with the help of additional information,
      such as RNA-Seq reads or EST libraries. However, none of these strategies is bias
      free and one method alone does not necessarily provide a complete set of accurate
      predictions. RESULTS: We present IPred (Integrative gene Prediction), a method to
      integrate ab initio and evidence based gene identifications to complement the
      advantages of different prediction strategies. IPred builds on the output of gene
      finders and generates a new combined set of gene identifications, representing
      the integrated evidence of the single method predictions. CONCLUSION: We evaluate
      IPred in simulations and real data experiments on Escherichia Coli and human
      data. We show that IPred improves the prediction accuracy in comparison to single
      method predictions and to existing methods for prediction combination.

PMID- 25766583
TI  - Release of Ciprofloxacin and Moxifloxacin From Daily Disposable Contact Lenses
      From an In Vitro Eye Model.
AB  - PURPOSE: To analyze the release of two fluoroquinolones, ciprofloxacin and
      moxifloxacin, from conventional hydrogel (CH) and silicone hydrogel (SH) daily
      disposable contact lenses (CLs), comparing release from a fixed-volume vial and a
      novel in vitro eye model. METHODS: Four CH CLs (nelfilcon A, omafilcon A,
      etafilcon A, ocufilcon B) and three SH CLs (somofilcon A, narafilcon A,
      delefilcon A) were used. The lenses were incubated in drug solutions for 24
      hours. After the incubation period, the lenses were placed in two release
      conditions: (1) a vial containing 4.8 mL PBS for 24 hours and (2) an in vitro eye
      model with a flow rate at 4.8 mL over 24 hours. RESULTS: Release in the vial for
      both drugs was rapid, reaching a plateau between 15 minutes and 2 hours for all
      lenses. In contrast, under physiological flow conditions, a constant and slow
      release was observed over 24 hours. The amounts of ciprofloxacin released from
      the lenses ranged between 49.6 +/- 0.7 and 62.8 +/- 0.3 MUg per lens in the vial,
      and between 35.0 +/- 7.0 and 109.0 +/- 5.0 MUg per lens in the eye model.
      Moxifloxacin release ranged from 24.0 +/- 4.0 to 226.0 +/- 2.0 MUg per lens for
      the vial, and between 13.0 +/- 2.0 and 151.0 +/- 10.0 MUg per lens in the eye
      model. In both systems and for both drugs, HEMA-based CLs released more drugs
      than other materials. CONCLUSIONS: The parameters of the release system, in
      particular the volume and flow rate, have a significant influence on measured
      release profiles. Under physiological flow, release profiles are significantly
      slower and constant when compared with release in a vial.

PMID- 25766584
TI  - Influence of the beta2-Subunit of L-Type Voltage-Gated Cav Channels on the
      Structural and Functional Development of Photoreceptor Ribbon Synapses.
AB  - PURPOSE: The cacnb2 gene encodes the beta2 subunit (Cavbeta2) of voltage-gated
      Ca2+ channels in photoreceptors, and its targeted deletion in mice has previously
      been shown to cause altered retinal morphology and synaptic transmission. The
      purpose of this study was to provide a detailed morphologic study combined with
      experiments on the altered functions of photoreceptor ribbon synapses lacking
      Cavbeta2. METHODS: A cacnb2-deficient mouse strain was generated and deletion of
      the Cavbeta2 in the retina documented by biochemical and immunhistochemical
      approaches. Ultrastructural changes of photoreceptor ribbon synapses were
      examined by electronmicroscopy and functional implications of the lack of
      Cavbeta2 studied by depolarization-induced Ca2+ influx into isolated
      photoreceptor cells and electroretinography. RESULTS: Voltage-gated Ca2+ influx
      into rod photoreceptors lacking Cavbeta2 was abolished and the typical rod ribbon
      type active zones were absent in Cavbeta2-deficient retinas. The active zone and
      the architecture of the presynaptic terminals were severely altered in rod
      synapses. Cone photoreceptor and the bipolar cell ribbon synapses were largely
      spared from ultrastructural changes although peanut agglutinin (PNA) labelling
      and photopic ERG analyses demonstrated that also cone pathways were disturbed in
      Cavbeta2-deficient retinas. CONCLUSIONS: The presence of the Cavbeta2 is
      essential for the structural integrity and function of the rod photoreceptor
      synapse. The Cavbeta2 is less essential for the morphology of cone and bipolar
      cell ribbon synapses, although the impaired photopic electroretinogram suggests a
      functional alteration also of the cone-mediated signaling in Cavbeta2-deficient
      retinas.

PMID- 25766585
TI  - Antiangiogenic Effectiveness of the Urokinase Receptor-Derived Peptide UPARANT in
      a Model of Oxygen-Induced Retinopathy.
AB  - PURPOSE: Pharmacologic control of neovascularization is a promising approach for
      the treatment of retinal angiogenesis. UPARANT, an inhibitor of the urokinase
      type plasminogen activator receptor (uPAR), inhibits VEGF-driven angiogenesis in
      vitro and in vivo. This study investigates for the first time the effectiveness
      of UPARANT in counteracting pathologic neovascularization in the retina. METHODS:
      Murine retinal fragments and a mouse model of oxygen-induced retinopathy (OIR)
      were used. In mice with OIR, UPARANT-treated retinas were analyzed for avascular
      area and neovascular tuft formation. Levels of transcription and proangiogenic
      factors were determined. UPARANT effects on the blood-retinal barrier (BRB),
      visual function, retinal cytoarchitecture, and inflammatory markers were also
      assessed. Human umbilical vein endothelial cells (HUVECs) and chick embryo
      chorioallantoic membrane (CAM) in which angiogenesis was induced by the vitreous
      fluid from patients with proliferative diabetic retinopathy (PDR) were also used.
      RESULTS: UPARANT reduced VEGF-induced angiogenesis in retinal fragments. In mice
      with OIR, UPARANT decreased neovascular response, VEGF, and VEGF receptor-2
      activity. Transcription factors regulating VEGF expression were also reduced.
      UPARANT restored BRB integrity, recovered visual loss, and reduced levels of
      inflammatory markers. Restored electroretinogram does not involve any rescue in
      the retinal cytoarchitecture. Finally, UPARANT blocked PDR vitreous fluid-induced
      angiogenesis in HUVEC and CAM assays. CONCLUSIONS: The finding that UPARANT is
      effective against neovascularization may help to establish uPAR as a target in
      the treatment of proliferative retinopathies. The potential application of
      UPARANT in retinal diseases is further supported by UPARANT capacity to
      counteract the angiogenic activity of PDR vitreous fluid.

PMID- 25766586
TI  - Difficulties With Goals of the Dutch ICF Activity Inventory: Perceptions of Those
      With Retinitis Pigmentosa and of Those Who Support Them.
AB  - PURPOSE: To provide a comprehensive overview of the perceived difficulties with
      visual activities and participation by those with retinitis pigmentosa (RP), and
      as perceived by those who support people with RP. Further, to examine the
      performance of the Dutch ICF Activity Inventory (D-AI) using Rasch analysis.
      METHODS: Three hundred fifty people with RP and 75 supporters of people with RP
      provided demographic information and completed the D-AI at goal level (47 goals).
      RESULTS: Following removal of four goals, the D-AI behaved well in Rasch
      analysis, but with limitations to its unidimensionality. The most difficult goals
      for people with RP related to mobility and to work-related activities. Greater
      difficulty was associated with higher visual impairment registration status, use
      of mobility aids, and longer duration of visual impairment. For those with less
      severe visual loss, goals relating to communicating with people were relatively
      more difficult. In more severe loss, goals involving good central vision (e.g.,
      dealing with correspondence) were relatively more difficult. The perceptions of
      supporters matched those of the people with RP relatively well, but with a
      tendency for supporters to overestimate the difficulty of goals, which related to
      administration and domestic chores, and to underestimate difficulty with goals
      relating to communication with people. CONCLUSIONS: The results indicate
      important areas of rehabilitation to address in addition to orientation and
      mobility in those with RP, including work-related activities and goals involving
      good central vision. Both people with RP and those supporting them could benefit
      from help addressing difficulties with communication.

PMID- 25766588
TI  - Sorsby Fundus Dystrophy: Novel Mutations, Novel Phenotypic Characteristics, and
      Treatment Outcomes.
AB  - PURPOSE: To report novel TIMP3 mutations, and to characterize the ocular
      phenotype of Sorsby fundus dystrophy (SFD), including a novel early sign for the
      disease and to report the effect of anti-VEGF therapy. METHODS: Twenty-one
      probands of three unrelated families with SFD were investigated using wide-field
      imaging, confocal laser scanning ophthalmoscopy with autofluorescence imaging,
      optical coherence tomography (OCT), indocyanine green-angiography (ICG-A), and
      molecular diagnostic for causative mutations. RESULTS: Molecular genetic analysis
      revealed two novel (p.Tyr174Cys, p.Tyr177Cys) and one previously described
      (p.Tyr182Cys) missense mutations in TIMP3. In families with p.Tyr177Cys and
      p.Tyr182Cys, metamorphopsia and/or decrease in visual acuity were the initial
      symptoms occurring at approximately the sixth decade of life. The p.Tyr174Cys
      mutation carriers had first symptoms at approximately the third decade with dark
      adaptation problems and visual field defects. The ocular phenotype included
      drusen-like deposits, rapidly progressive geographic atrophy, choroidal
      neovascularization (CNV), and polypoidal choroidal neovascularization (PCV). Late
      disease manifestations were uniform with widespread chorioretinal atrophy,
      fibrosis, and choroidal thinning. Three asymptomatic young carriers of a TIMP3
      mutation with otherwise normal findings on funduscopy and retinal imaging showed
      a characteristically reduced fluorescence on late-phase ICG-A images. This
      phenotypic sign was more pronounced and widespread in later disease stages.
      Patients with CNV or PCV showed a favorable response to therapy with
      intravitreally injected bevacizumab. CONCLUSIONS: This study expands the spectrum
      of mutations in the TIMP3 gene and associated phenotypic findings. Imaging using
      late-phase ICG-A may be useful for early identification of individuals at risk
      for developing SFD. Intravitreal anti-VEGF therapy if initiated timely is
      effective in SFD patients with CNV.

PMID- 25766589
TI  - Lack of Interphotoreceptor Retinoid Binding Protein Caused by Homozygous Mutation
      of RBP3 Is Associated With High Myopia and Retinal Dystrophy.
AB  - PURPOSE: We present a detailed clinical and molecular study of four patients from
      two consanguineous families with a similar childhood-onset retinal dystrophy
      resulting from novel homozygous nonsense mutations in RBP3. METHODS: Four
      children with mutations in RBP3 encoding interphotoreceptor binding protein
      (IRBP) were ascertained by whole exome sequencing and subsequent direct Sanger
      sequencing. Detailed phenotyping was performed, including full clinical
      evaluation, electroretinography, fundus photography, fundus autofluorescence
      (FAF) imaging, and spectral-domain optical coherence tomography (OCT). RESULTS:
      Two novel homozygous nonsense mutations (c.1530T>A;p.Y510* and
      c.3454G>T;p.E1152*) in RBP3 were identified in four patients from two families.
      All four patients had a similar, unusual retinal dystrophy characterized by
      childhood onset high myopia, generalized rod and cone dysfunction, and an
      unremarkable fundus appearance. The FAF imaging showed multiple paracentral foci
      of low autofluorescence in one patient and patchy increased FAF in the region of
      the vascular arcades in another. The OCT showed loss of outer retinal bands over
      peripheral macular areas in all 4 cases. CONCLUSIONS: To our knowledge, this
      report is the first to describe the retinal dystrophy in children caused by
      homozygous nonsense RBP3 mutations, highlighting the requirement for IRBP in
      normal eye development and visual function. Longitudinal study will reveal if the
      four children reported here will progress to a more typical retinitis pigmentosa
      phenotype described previously in adults with RBP3 mutations. The RBP3-related
      disease should be considered in children with high myopia and retinal dystrophy,
      particularly when there are no significant fundus changes.

PMID- 25766591
TI  - Regional diffusion of botulinum toxin in facial muscles: a randomised double
      blind study and a consideration for clinical studies with split-face design.
AB  - Despite the extensive use of botulinum toxin A (BoNTA) in medical and cosmetic
      treatments, the potential spreading of BoNTA to surrounding tissues remains
      unknown. A patient with hemifacial paralysis upon blepharospasm treatment with
      low dose of BoNTA, prompted us to investigate the spreading effect. A randomised,
      double-blind study was conducted in which 5 healthy women (33-52 years) were
      treated with different doses of onabotulinum toxin unilaterally in the corrugator
      muscle. Parameters of efficacy and diffusion (CMAP; EMG and jitter analysis) in
      both glabellar and frontalis muscles were assessed at baseline, 2 and 4 weeks
      following BoNTA injection. CMAP of the treated glabellar muscles was reduced to
      approximately 40% in all dose groups. Additionally, contralateral CMAP reduction
      was observed in 3 of 5 subjects. These data confirm regional diffusion of BoNTA
      in facial muscle application, which raises question on the reliability of split
      face models in BoNTA studies. 

PMID- 25766590
TI  - Retinal Ganglion Cell Loss and Mild Vasculopathy in Methylene Tetrahydrofolate
      Reductase (Mthfr)-Deficient Mice: A Model of Mild Hyperhomocysteinemia.
AB  - PURPOSE: Methylenetetrahydrofolate reductase (Mthfr) is a key enzyme in
      homocysteine-methionine metabolism. We investigated Mthfr expression in retina
      and asked whether mild hyperhomocysteinemia, due to Mthfr deficiency, alters
      retinal neurovascular structure and function. METHODS: Expression of Mthfr was
      investigated at the gene and protein level using quantitative (q) RT-PCR, in situ
      hybridization, immunoblotting, and immunohistochemistry (IHC). The Mthfr+/+ and
      Mthfr+/- mice were subjected to comprehensive evaluation using ERG, funduscopy,
      fluorescein angiography (FA), spectral-domain optical coherence tomography (SD
      OCT), HPLC, and morphometric and IHC analysis of glial fibrillary acidic protein
      (GFAP) at 8 to 24 weeks. RESULTS: Gene and protein analyses disclosed widespread
      retinal expression of Mthfr. Electroretinography (ERG) revealed a significant
      decrease in positive scotopic threshold response in retinas of Mthfr+/- mice at
      24 weeks. Fundus examination in mice from both groups was normal; FA revealed
      areas of focal vascular leakage in 20% of Mthfr+/- mice at 12 to 16 weeks and 60%
      by 24 weeks. The SD-OCT revealed a significant decrease in nerve fiber layer
      (NFL) thickness at 24 weeks in Mthfr+/- compared to Mthfr+/+ mice. There was a 2
      fold elevation in retinal hcy at 24 weeks in Mthfr+/- mice by HPLC and IHC.
      Morphometric analysis revealed an approximately 20% reduction in cells in the
      ganglion cell layer of Mthfr+/- mice at 24 weeks. The IHC indicated significantly
      increased GFAP labeling suggestive of Muller cell activation. CONCLUSIONS: Mildly
      hyperhomocysteinemic Mthfr+/- mice demonstrate reduced ganglion cell function,
      thinner NFL, and mild vasculopathy by 24 weeks. The retinal phenotype is similar
      to that of hyperhomocysteinemic mice with deficiency of cystathionine-beta
      synthase (Cbs) reported earlier. The data support the hypothesis that
      hyperhomocysteinemia may be causative in certain retinal neurovasculopathies.

PMID- 25766592
TI  - Effects of a High-Protein/Low-Carbohydrate versus a Standard Hypocaloric Diet on
      Weight and Cardiovascular Risk Factors during 9 Months: Role of a Genetic
      Variation in the Cannabinoid Receptor Gene (CNR1) (G1359A Polymorphism).
AB  - OBJECTIVE: We decided to investigate the role of this polymorphism on
      cardiovascular risk factors and weight loss secondary to a high-protein/low
      carbohydrate vs. a standard hypocaloric diet (1,000 kcal/day) over a period of 9
      months. MATERIAL AND METHODS: A nutritional evaluation was performed at the
      beginning and at the end of a 9-month period in which subjects received 1 of 2
      diets (diet HP: high protein/low carbohydrate vs. S: standard diet). RESULTS: One
      hundred and four patients (54.7%) had the genotype G1359G and 86 (45.3%) patients
      had G1359A (77 patients, 25.8%) or A1359A (9 patients, 3.7%) (A-allele-carriers).
      In subjects with both genotypes, the body mass index, weight, fat mass, waist
      circumference and systolic blood pressures decreased with both diets. After the
      diet type HP and in subjects with both genotypes, the glucose, leptin, total
      cholesterol, LDL-cholesterol, insulin and HOMA-R levels decreased. After diet S
      and in all subjects, the total cholesterol, LDL cholesterol and leptin levels
      decreased, too. CONCLUSION: Our interventional study didn't show a relationship
      between the rs1049353 CNR-1 polymorphism and body weight response after two
      different hypocaloric (low carbohydrate/high protein vs. standard) diets over a
      period of 9 months. However, a low-carbohydrate/high-protein diet for 9 months
      improved glucose metabolism in subjects with both genotypes.

PMID- 25766593
TI  - A porcine reproductive and respiratory syndrome virus vaccine candidate based on
      PRRSV glycoprotein 5 and the Toll-like receptor 5 agonist Salmonella typhimurium
      flagellin.
AB  - Glycoprotein 5 (GP5) from porcine reproductive and respiratory syndrome virus
      (PRRSV) is a key inducer of neutralizing antibodies. A truncated GP5 gene lacking
      the signal peptide and transmembrane sequences was amplified via an overlap PCR
      method and inserted into prokaryotic expression vectors, pET32a or pGEX-6p-1, to
      add an His or GST tag, respectively. His-tagged GP5 was induced with IPTG,
      verified by SDS-PAGE and Western blotting, and purified to serve as an immunogen
      accompanied with the Salmonella typhimurium flagellin (FliC), a Toll-like
      receptor 5 (TLR5) agonist. Levels of TLR5 and cytokine mRNAs in spleens of mice
      following injection with FliC were detected by qRT-PCR to verify the activation
      of innate immunity. FliC was used as an adjuvant and administered with the GP5 to
      C57BL/6 mice via intraperitoneal injection. Coadministration of GP5 with FliC
      induced a significantly enhanced GP5-specific IgG and IFN-gamma response compared
      with administration of GP5 alone, and the GP5-specific titer in the GP5 + FliC
      coadministration group was elevated almost twofold after the third immunization.
      These results indicate that FliC is an effective adjuvant, increasing the
      induction of antibodies against GP5 with the induction of both humoral and
      cellular immune responses.

PMID- 25766594
TI  - Investigational drugs for affective disorders. Foreword.

PMID- 25766597
TI  - Meniere's disease: histopathology, cytochemistry, and imaging.
AB  - Meniere's disease is a poorly understood, disabling syndrome causing spells of
      vertigo, hearing fluctuation, tinnitus, and aural fullness. In this paper, we
      present a review of the histopathology, cytochemistry, and imaging of Meniere's
      disease. Histopathology is significant for neuroepithelial damage with hair cell
      loss, basement membrane thickening, and perivascular microvascular damage.
      Cytochemical alterations are significant for altered AQP4 and AQP6 expression in
      the supporting cell, and altered cochlin and mitochondrial protein expression.
      Current developments include imaging techniques to determine the degree and
      presence of endolymphatic hydrops, and future studies will endeavor to correlate
      the observance of hydrops with clinical findings. 

PMID- 25766596
TI  - Targeting FcRn for the modulation of antibody dynamics.
AB  - The MHC class I-related receptor, FcRn, is a multitasking protein that transports
      its IgG ligand within and across cells of diverse origins. The role of this
      receptor as a global regulator of IgG homeostasis and transport, combined with
      knowledge of the molecular details of FcRn-IgG interactions, has led to
      opportunities to modulate the in vivo dynamics of antibodies and their antigens
      through protein engineering. Consequently, the generation of half-life extended
      antibodies has shown a rapid expansion over the past decade. Further, FcRn itself
      can be targeted by inhibitors to induce decreased levels of circulating IgGs,
      which could have applications in multiple clinical settings. The engineering of
      antibody-antigen interactions to reduce antibody-mediated buffering of soluble
      ligand has also developed into an active area of investigation, leading to novel
      antibody platforms designed to result in more effective antigen clearance.
      Similarly, the target-mediated elimination of antibodies by internalizing,
      membrane bound antigens (receptors) can be decreased using novel engineering
      approaches. These strategies, combined with subcellular trafficking analyses of
      antibody/antigen/FcRn behavior in cells to predict in vivo behavior, have
      considerable promise for the production of next generation therapeutics and
      diagnostics. 

PMID- 25766598
TI  - Morphometry of the amygdala in schizophrenia and psychotic bipolar disorder.
AB  - Volumetric studies suggest smaller amygdalae in subjects with schizophrenia (SZ)
      than with bipolar disorder (BP). We use morphometry to identify subregions of
      amygdala differentially affected in SZ and psychotic BP. Based on template
      centered population analysis, the shape of the amygdala in psychotic BP differs
      from SZ (pleft=0.044, pright=0.042). Using a high-field 7 T atlas, the bilateral
      basolateral, basomedial and centromedial subregions and the right lateral
      subregion were significantly atrophied in SZ compared to psychotic BP (p<0.02).
      These results suggest that change in shape of amygdala may represent a
      morphologic feature distinguishing SZ from psychotic BP.

PMID- 25766599
TI  - Human urine is not sterile - shift of paradigm.
AB  - OBJECTIVE: Until recently the generally accepted paradigm implied that urine of
      healthy people is sterile. In the present study, urine of healthy subjects was
      investigated by extended bacteriological methods. MATERIAL AND METHODS: Three
      midstream urine samples from 52 healthy subjects each (24 females, 28 males; 18
      25 years of age) were investigated by an extended set of culture media for
      identification of facultative aerobic (FAB) and nonclostridial anaerobic bacteria
      (NCAB). Ward's method (Euclidean distance) was used for similarity analysis.
      RESULTS: The bacterial count of FAB in urine was usually low (<= 10(2) colony
      forming units/ml) in both groups. In contrast, the bacterial count of NCAB was
      higher (>= 10(3) colony-forming units/ml), at least in some species, with
      significant differences between genders. The average number of bacterial species
      found was 5.8 in female and 7.1 in male urine. Half of the females were assigned
      to a specific 'female' microbial spectrum, different from that of males. In the
      mixed-gender clusters, the males showed a greater similarity among themselves.
      CONCLUSIONS: As also shown by other investigators, urine of healthy people is
      normally not sterile. The role of the routinely not cultivated bacteria in
      healthy and diseased subjects needs to be established. It may alter the
      diagnostics of infectious and inflammatory diseases of the urogenital tract.

PMID- 25766600
TI  - A mutasynthesis approach with a Penicillium chrysogenum DeltaroqA strain yields
      new roquefortine D analogues.
AB  - Penicillium chrysogenum, which lacks the roqA gene, processes synthetic,
      exogenously added histidyltryptophanyldiketopiperazine (HTD) to yield a set of
      roquefortine-based secondary metabolites also produced by the wild-type strain.
      Feeding a number of synthetic HTD analogues to the DeltaroqA strain gives rise to
      the biosynthesis of a number of new roquefortine D derivatives, depending on the
      nature of the synthetic HTD added. Besides delivering semisynthetic roquefortine
      analogues, the mutasynthesis studies presented here also shed light on the
      substrate preferences and molecular mechanisms employed by the roquefortine C/D
      biosynthesis gene cluster, knowledge that may be tapped for the future
      development of more complex semisynthetic roquefortine-based secondary
      metabolites. 

PMID- 25766601
TI  - Detecting Dengue Virus Nonstructural Protein 1 (NS1) in Urine Samples Using ELISA
      for the Diagnosis of Dengue Virus Infection.
AB  - Dengue virus (DENV) infection is a serious global health threat. For the
      surveillance and control of dengue, there is a need for robust diagnostic tools
      that are relatively easy to use and reliable in various clinical settings. We
      investigated the applicability of NS1 antigen detection in urine samples for the
      diagnosis of DENV. About 118 urine samples, obtained from 96 dengue patients at
      various phases of disease, were used for this study. NS1 antigen was detected by
      ELISA in the urine samples obtained from patients after 2-17 days of disease
      onset. Positive detection rates of NS1 antigen ranged between 13-43%. Based on
      real-time RT-PCR, positive detection rates of viral genome in the urine samples
      ranged between 20-33% on days 0 to >=15. On days 11 to >=15 after the disease
      onset, NS1 antigen was detected at similar rates in serum and urine samples.
      Additionally, NS1 antigen was detected in 2 urine samples, but not in the serum
      samples, on days 7 and 16 after the onset of the disease. The results confirm the
      applicability of NS1 antigen detection in urine samples using ELISA to diagnose
      acute DENV infection and suggests that the assay is potentially useful when only
      limited amounts of serum samples are available and in limited resource settings. 

PMID- 25766602
TI  - Immunogenicity of a Candidate DNA Vaccine Based on the prM/E Genes of a Dengue
      Type 2 Virus Cosmopolitan Genotype Strain.
AB  - The development of a dengue virus vaccine is a major priority in efforts to
      control the diseases. Several researchers are currently using the Asian 1 and
      Asian 2 genotypes as vaccine candidates for dengue type 2 virus (DENV-2).
      However, in this study, we constructed a recombinant plasmid-based prM/E gene,
      from a DENV-2 Cosmopolitan genotype strain as a dengue DNA vaccine candidate. The
      protein expression of the recombinant plasmid in CHO cells was analyzed using an
      enzyme-linked immunosorbent assay, western blotting, and sucrose gradient
      sedimentation. After being used to immunize ddY mice three times at doses of 25
      or 100 MUg, the DNA vaccine induced humoral immune responses. There was no
      difference in the neutralizing antibody titer (focus reduction neutralization
      test 50% value) of mice immunized with 25 and 100 MUg DNA vaccine doses. When
      challenged with 3 * 10(5) FFU DENV-2, immunized mice could raise anamnestic
      neutralizing antibody responses, which were observed at day 4 and day 8 post
      challenge. Analysis of immunogenicity using BALB/c mice showed that their
      antibody neutralization titers were lower than those of ddY mice. In addition,
      the antibodies produced after immunization and challenge could also neutralize a
      DENV-2 Asian 2 genotype (New Guinea C) strain. Therefore, the DENV-2 Cosmopolitan
      genotype may be a DENV-2 vaccine candidate. 

PMID- 25766603
TI  - Sexual Practices and the Prevalence of HIV and Syphilis among Men Who Have Sex
      with Men in Lanzhou, China.
AB  - We aimed to assess the risk of infections caused by sexual practices and
      determine the factors affecting the prevalence of human immunodeficiency virus
      (HIV) and syphilis among men who have sex with men (MSM) in Lanzhou, China. A
      survey including 600 MSM was conducted from March 2008 to December 2009.
      Demographic and sexual behavior data were collected using the snowball sampling
      technology, and blood samples were obtained. Multivariate logistic regression
      models were used to determine the predictors of HIV and syphilis infection. The
      seroprevalence of HIV, syphilis, HCV, and co-infection of HIV with syphilis was
      6.0%, 18.0%, 1.3%, and 2.5%, respectively. Use of condoms was more inconsistent
      in vaginal sex than that in anal sex, buying sex or selling sex. Multivariate
      analysis showed that MSM with syphilis infection, MSM from other provinces, and
      MSM of Han ethnicity were more likely to have HIV infection. Further, MSM with
      HIV infection, inconsistent condom use, and less knowledge about AIDS prevention
      were more likely to have syphilis infection. Their social background, habit of
      condom use, and infection status may affect the prevalence of HIV or syphilis.
      These findings may have important implications for further behavioral
      interventions among this population. 

PMID- 25766604
TI  - Pseudomonas oleovorans Sepsis in a Child: The First Reported Case in India.

PMID- 25766605
TI  - Genomic Analysis of Single Nucleotide Polymorphisms Asp299Gly and Thr399Ile in
      Japanese Patients with Invasive Aspergillosis.
AB  - Single nucleotide polymorphisms (SNPs) 1063A/G (Asp299Gly) and 1363C/T
      (Thr399Ile) in the gene encoding Toll-like receptor 4 (TLR4) increase
      susceptibility to invasive aspergillosis. However, limited information is
      available on the prevalence of these SNPs in Japan. Therefore, we surveyed these
      TLR4 SNPs by using formalin-fixed and paraffin-embedded tissue blocks obtained
      from autopsies of patients with invasive pulmonary aspergillosis. Tissue samples
      of approximately 30% patients were included in genomic analysis. However, none of
      these samples showed the presence of TLR4 Asp299Gly and Thr399Ile polymorphisms.
      Thus, the present study provided information on the prevalence of TLR4 SNPs in
      Japanese patients with invasive aspergillosis and indicated that these SNPs
      played a minor role in increasing the susceptibility of Japanese individuals to
      invasive aspergillosis. 

PMID- 25766606
TI  - Multidrug-Resistant Vibrio cholerae O1 was Responsible for a Cholera Outbreak in
      2013 in Bagalkot, North Karnataka.
AB  - Cholera is a major cause of illness in the developing world. During the monsoon
      season, small sporadic clusters of cholera cases are reported on an annual basis
      in Karnataka, India. During the monsoons of 2013, there was a cholera outbreak in
      Badami, a remote area of Bagalkot district in Karnataka. The multi-drug-resistant
      Vibrio cholerae O1 serotype Ogawa was found to be responsible for this outbreak.
      On 5 August 2013, a 30-year-old woman presented with severe dehydration and
      watery diarrhea at the Aganwadi Health Centre in Badami. A total of 49 suspected
      cholera cases were reported, with an attack rate of 3.5%. The V. cholerae
      isolates exhibited resistance to a wide range of drugs, including ampicillin, co
      trimoxazole, nitrofurantoin, carbenicillin, and third generation cephalosporins,
      and showed reduced susceptibility to third generation fluoroquinolones. All of
      the cephalosporin-resistant V. cholerae strains produced extended-spectrum beta
      lactamase. All V. cholerae O1 isolates harbored virulent genes (ctxA, ctxB, tcpA
      El Tor, Tox S, VPI, ToxT, ToxR, ToxRS, ace, zot, and tcpP) and were found to be
      genetically similar as determined by randomly amplified polymorphic DNA
      fingerprinting assay. To the best of our knowledge, this is the first report of a
      cholera outbreak in the district of Bagalkot. The resistance of V. cholerae to
      commonly used antimicrobial drugs is becoming a major public health concern in
      the region as clinicians are left with a limited choice of antibiotics for the
      treatment of cholera. 

PMID- 25766607
TI  - Active Surveillance of Methicillin-Resistant Staphylococcus aureus Using a Fully
      Automated Molecular Test in an Emergency Medical Center.
AB  - The prevention and control of methicillin-resistant Staphylococcus aureus (MRSA)
      are important, particularly in emergency units. The active surveillance of MRSA
      was prospectively performed at the emergency medical center of Nagasaki
      University Hospital. After obtaining nasal swab specimens, a fully automated
      molecular test (FAMT) and a culture-screening method were utilized for MRSA
      detection. A total of 150 patients were enrolled in the study, and 366 nasal swab
      specimens were obtained. MRSA was detected by culture in 11 (7.3%) patients
      including one new acquisition and by the FAMT in 34 (22.7%) patients including 13
      new acquisitions. The sensitivity, specificity, positive predictive value, and
      negative predictive value of the FAMT at the patient level were 86.7, 85.2, 39.4,
      and 98.3%, respectively, when compared with the culture-based results. An FAMT
      can effectively detect MRSA colonization, which may remain undetected with the
      conventional method, and it may be useful in detecting newly acquired MRSAs. 

PMID- 25766608
TI  - Coexistence of Avian Influenza Virus H10 and H9 Subtypes among Chickens in Live
      Poultry Markets during an Outbreak of Infection with a Novel H10N8 Virus in
      Humans in Nanchang, China.
AB  - Infection with the novel H10N8 virus in humans has raised concerns about its
      pandemic potential worldwide. We report the results of a cross-sectional study of
      avian influenza viruses (AIVs) in live poultry markets (LPMs) in Nanchang, China,
      after the first human case of H10N8 virus infection was reported in the city. A
      total of 201 specimens tested positive for AIVs among 618 samples collected from
      24 LPMs in Nanchang from December 2013 to January 2014. We found that the LPMs
      were heavily contaminated by AIVs, with H9, H10, and H5 being the predominant
      subtypes and more than half of the LPMs providing samples that were positive for
      the H10 subtype. Moreover, the coexistence of different subtypes was common in
      LPMs. Of the 201 positive samples, 20.9% (42/201) had mixed infections with AIVs
      of different HA subtypes. Of the 42 mixed infections, 50% (21/42) showed the
      coexistence of the H9 and H10 subtypes, with or without H5, and were from chicken
      samples. This indicated that the H10N8 virus probably originated from segment
      reassortment of the H9 and H10 subtypes. 

PMID- 25766609
TI  - Severe Toxoplasmic Hepatitis in an Immunocompetent Patient.
AB  - Acute Toxoplasma gondii infection causes different clinical courses in 10-20% of
      cases. In immunocompetent patients, toxoplasmosis most often presents as
      asymptomatic cervical lymphadenopathy. Clinical manifestations such as pneumonia,
      myocarditis, hepatitis, and encephalitis are rarely reported. We present the case
      of an immunocompetent patient with a serious and complicated clinical course of
      toxoplasmic hepatitis with a maculopapular rash. The diagnosis was confirmed by
      serology and identification of bradyzoites in liver biopsy samples. 

PMID- 25766610
TI  - Turtle-Associated Salmonella Infections in Kanagawa, Japan.
AB  - In this paper, we examine 2 case reports for different reptile-related Salmonella
      enterica subspecies enterica serotypes. In case 1, a 5-year-old boy presented
      with gastroenteritis caused by S. enterica subspecies enterica serovar Poona. The
      suspected source of infection was a turtle kept at the patient's home. In case 2,
      a 4-year-old boy presented with gastroenteritis caused by S. enterica subspecies
      enterica serovar Abony. The Pulsed-field gel electrophoresis analysis suggested
      that a tortoise kept at the patient's home was the source of infection. This
      paper presents a review of the literature and an examination of cases regarding
      turtle-associated salmonellosis in Japan. 

PMID- 25766611
TI  - Susceptibility of Indigenous and Transplanted Mosquito Spp. to Dengue Virus in
      Japan.
AB  - Dengue fever, an acute, mosquito-borne, febrile illness caused by Flavivirus
      spp., is a problem in Africa, South and Southeast Asia, Latin America, and the
      Caribbean. A dengue outbreak occurred after nearly 70 years of absence or no
      detection, and then 158 autochthonous cases occurred in Japan from August to
      October 15, 2014. The most competent mosquito vectors for dengue virus
      transmission were Aedes aegypti and A. albopictus. Since A. albopictus is widely
      distributed across Japan and A. aegypti recently invaded Japan by airplane, we
      examined the susceptibility of these species to infection by dengue virus. 

PMID- 25766612
TI  - Association between RABV G Proteins Transported from the Perinuclear Space to the
      Cell Surface Membrane and N-Glycosylation of the Sequon Asn(204).
AB  - In this study, G proteins of the rabies virus (RABV) Kyoto strain were detected
      in the cytoplasm but not distributed at the cell membrane of mouse neuroblastoma
      (MNA) cells. G proteins of CVS-26 were detected in both the cell membrane and
      perinuclear space of MNA cells. We found that N-glycosylation of street RABV G
      protein by the insertion of the sequon Asn(204) induced the transfer of RABV G
      proteins to the cell surface membrane. Fixed RABV budding from the plasma
      membrane has been found to depend not only on G protein but also on other
      structural proteins such as M protein. However, the differing N-glycosylation of
      G protein could be associated with the distinct budding and antigenic features of
      RABV in street and fixed viruses. Our study of the association of N-glycan of G
      protein at Asn(204) with the transport of RABV G protein to the cell surface
      membrane contributes to the understanding of the evolution of fixed virus from
      street virus, which in turn would help for determine the mechanism underlying
      RABV budding and enhanced host immune responses. 

PMID- 25766613
TI  - Biting Density and Distribution of Aedes albopictus during the September 2014
      Outbreak of Dengue Fever in Yoyogi Park and the Vicinity of Tokyo Metropolis,
      Japan.
AB  - A total of 160 autochthonous dengue cases transmitted by Aedes albopictus were
      reported between August and October of 2014 in Tokyo Metropolis, Japan. Ae.
      albopictus is a medically important vector of dengue virus, which has expanded
      its geographic distribution in temperate regions. Understanding the distribution
      and biting density of Ae. albopictus during the 2014 dengue outbreak in Tokyo is
      important to evaluate the epidemic risks of dengue fever in other highly
      populated cities in Europe and Asia. Of the 160 patients, 134 visited the same
      park (Yoyogi Park) located in central Tokyo. Mosquitoes infected with dengue
      virus were collected from this park, suggesting that it was the exclusive
      location for the transmission of dengue. This study aimed to collect referential
      data to estimate the transmission threshold of dengue virus in terms of biting
      density of Ae. albopictus and determined high transmission risk areas of dengue
      virus in Yoyogi Park and its vicinity. The overall mean density of biting Ae.
      albopictus (7.13/man/8 min) was sufficiently high for successful transmission of
      dengue virus, and areas with biting densities higher than the overall mean
      density were classified as high risk areas for the transmission of dengue virus
      in Yoyogi Park.

PMID- 25766614
TI  - Genetic variations of human papillomavirus type 16: implications for cervical
      carcinogenesis.
AB  - Human papillomaviruses (HPVs) are the causative agent of cervical cancer, and
      among approximately 15 high-risk genotypes, HPV16 accounts for more than half the
      cases of cervical cancer worldwide. Recent progress in determining HPV genomic
      sequences from clinical samples has revealed a wide variety in HPV16 genome
      sequences, and has allowed for comprehensive classification of intratype HPV16
      variants. These consist of four variant lineages containing nucleotide variations
      in 1.0%-10.0% of the complete viral genome sequence. Epidemiological data suggest
      that the non-European-Asian lineages of HPV16 entail a higher risk of progression
      to invasive cervical cancer than the European-Asian lineage. Deep sequencing
      analysis has recently demonstrated that HPV16 genome sequences are highly
      homogeneous in individual clinical specimens compared with those of RNA viruses.
      However, an extremely sensitive PCR method, differential DNA denaturation PCR,
      has detected hypermutations from C to T or G to A in the E2 gene and the long
      control region of the HPV16 genome, which suggests the involvement of cellular
      apolipoprotein B mRNA editing enzyme, catalytic polypeptide-like (APOBEC)
      proteins in this hypermutation. The quasispecies status of the HPV16 genome in
      the infected cervix may affect the development of cervical cancer and warrants
      further investigation. 

PMID- 25766615
TI  - Special issue on neurodegenerative diseases and their therapeutic approaches.

PMID- 25766616
TI  - Degradation of misfolded proteins in neurodegenerative diseases: therapeutic
      targets and strategies.
AB  - Mammalian cells remove misfolded proteins using various proteolytic systems,
      including the ubiquitin (Ub)-proteasome system (UPS), chaperone mediated
      autophagy (CMA) and macroautophagy. The majority of misfolded proteins are
      degraded by the UPS, in which Ub-conjugated substrates are deubiquitinated,
      unfolded and cleaved into small peptides when passing through the narrow chamber
      of the proteasome. The substrates that expose a specific degradation signal, the
      KFERQ sequence motif, can be delivered to and degraded in lysosomes via the CMA.
      Aggregation-prone substrates resistant to both the UPS and the CMA can be
      degraded by macroautophagy, in which cargoes are segregated into autophagosomes
      before degradation by lysosomal hydrolases. Although most misfolded and
      aggregated proteins in the human proteome can be degraded by cellular protein
      quality control, some native and mutant proteins prone to aggregation into beta
      sheet-enriched oligomers are resistant to all known proteolytic pathways and can
      thus grow into inclusion bodies or extracellular plaques. The accumulation of
      protease-resistant misfolded and aggregated proteins is a common mechanism
      underlying protein misfolding disorders, including neurodegenerative diseases
      such as Huntington's disease (HD), Alzheimer's disease (AD), Parkinson's disease
      (PD), prion diseases and Amyotrophic Lateral Sclerosis (ALS). In this review, we
      provide an overview of the proteolytic pathways in neurons, with an emphasis on
      the UPS, CMA and macroautophagy, and discuss the role of protein quality control
      in the degradation of pathogenic proteins in neurodegenerative diseases.
      Additionally, we examine existing putative therapeutic strategies to efficiently
      remove cytotoxic proteins from degenerating neurons. 

PMID- 25766617
TI  - Sleep, circadian rhythms, and the pathogenesis of Alzheimer disease.
AB  - Disturbances in the sleep-wake cycle and circadian rhythms are common symptoms of
      Alzheimer Disease (AD), and they have generally been considered as late
      consequences of the neurodegenerative processes. Recent evidence demonstrates
      that sleep-wake and circadian disruption often occur early in the course of the
      disease and may even precede the development of cognitive symptoms. Furthermore,
      the sleep-wake cycle appears to regulate levels of the pathogenic amyloid-beta
      peptide in the brain, and manipulating sleep can influence AD-related pathology
      in mouse models via multiple mechanisms. Finally, the circadian clock system,
      which controls the sleep-wake cycle and other diurnal oscillations in mice and
      humans, may also have a role in the neurodegenerative process. In this review, we
      examine the current literature related to the mechanisms by which sleep and
      circadian rhythms might impact AD pathogenesis, and we discuss potential
      therapeutic strategies targeting these systems for the prevention of AD. 

PMID- 25766618
TI  - Insulin resistance as a key link for the increased risk of cognitive impairment
      in the metabolic syndrome.
AB  - Metabolic syndrome (MetS) is a cluster of cardiovascular risk factors that
      includes obesity, diabetes, and dyslipidemia. Accumulating evidence implies that
      MetS contributes to the development and progression of Alzheimer's disease (AD);
      however, the factors connecting this association have not been determined.
      Insulin resistance (IR) is at the core of MetS and likely represent the key link
      between MetS and AD. In the central nervous system, insulin plays key roles in
      learning and memory, and AD patients exhibit impaired insulin signaling that is
      similar to that observed in MetS. As we face an alarming increase in obesity and
      T2D in all age groups, understanding the relationship between MetS and AD is
      vital for the identification of potential therapeutic targets. Recently, several
      diabetes therapies that enhance insulin signaling are being tested for a
      potential therapeutic benefit in AD and dementia. In this review, we will discuss
      MetS as a risk factor for AD, focusing on IR and the recent progress and future
      directions of insulin-based therapies. 

PMID- 25766619
TI  - The role of mitochondrial DNA mutation on neurodegenerative diseases.
AB  - Many researchers have reported that oxidative damage to mitochondrial DNA (mtDNA)
      is increased in several age-related disorders. Damage to mitochondrial
      constituents and mtDNA can generate additional mitochondrial dysfunction that may
      result in greater reactive oxygen species production, triggering a circular chain
      of events. However, the mechanisms underlying this vicious cycle have yet to be
      fully investigated. In this review, we summarize the relationship of oxidative
      stress-induced mitochondrial dysfunction with mtDNA mutation in neurodegenerative
      disorders. 

PMID- 25766620
TI  - Stem cell therapy for Alzheimer's disease and related disorders: current status
      and future perspectives.
AB  - Underlying cognitive declines in Alzheimer's disease (AD) are the result of
      neuron and neuronal process losses due to a wide range of factors. To date, all
      efforts to develop therapies that target specific AD-related pathways have failed
      in late-stage human trials. As a result, an emerging consensus in the field is
      that treatment of AD patients with currently available drug candidates might come
      too late, likely as a result of significant neuronal loss in the brain. In this
      regard, cell-replacement therapies, such as human embryonic stem cell- or induced
      pluripotent stem cell-derived neural cells, hold potential for treating AD
      patients. With the advent of stem cell technologies and the ability to transform
      these cells into different types of central nervous system neurons and glial
      cells, some success in stem cell therapy has been reported in animal models of
      AD. However, many more steps remain before stem cell therapies will be clinically
      feasible for AD and related disorders in humans. In this review, we will discuss
      current research advances in AD pathogenesis and stem cell technologies;
      additionally, the potential challenges and strategies for using cell-based
      therapies for AD and related disorders will be discussed. 

PMID- 25766621
TI  - Patient and tumor characteristics predictive of primary parotid gland malignancy:
      A 20-year experience at the University of Wisconsin.
AB  - PURPOSE: To identify patient and tumor characteristics predictive of primary
      parotid malignancy. MATERIALS AND METHODS: Records were reviewed for patients who
      underwent parotidectomy at the University of Wisconsin from 1994 to 2013.
      Patients with primary parotid neoplasms were separated into benign or malignant
      subgroups. A multivariate logistic regression model was employed to compare
      categorical (gender, lesion side, nature of presentation, recurrence) and
      numerical variables (age, tumor size) between the benign and malignant groups.
      Mean BMI was compared between the groups by univariate analysis. RESULTS: 771
      patients underwent parotidectomy from 1994 to 2013, and 474 had a primary parotid
      neoplasm. No relationship existed between malignancy and gender (p=0.610), lesion
      side (p=0.110), or BMI (p=0.196). Mean age (p=0.015) and tumor size (p=0.011)
      were significantly different between the benign and malignant groups. Patient
      presentation was classified into three categories: symptomatic (n=109), palpable
      and asymptomatic (n=303), and incidentally noted on imaging (n=57). From all
      patients with symptomatic, asymptomatic or incidentally noted masses, 41.3%,
      10.6% and 5.3%, respectively, were diagnosed with malignant disease. There was a
      significant relationship between the patient's initial presentation and
      malignancy (p<0.001), and patients with facial nerve dysfunction or skin
      involvement had the greatest likelihood of malignancy. Finally, there was a
      significant association between malignancy and recurrence (p=0.001). CONCLUSIONS:
      In this study, age, tumor size, and nature of presentation were all associated
      with primary parotid malignancy. Understanding the impact of these features on
      the probability of malignancy is valuable in decision making and counseling of
      patients presenting with a newly diagnosed parotid neoplasm.

PMID- 25766622
TI  - Evaluation of middle ear pressure in the early period after adenoidectomy in
      children with adenoid hypertrophy without otitis media with effusion.
AB  - OBJECTIVE: Our aim was to analyze the changes in middle ear pressure in the early
      period after adenoidectomy in children with adenoid hypertrophy without otitis
      media with effusion. METHODS: This prospective, descriptive study was performed
      on 64 patients (with normal tympanic membranes and tympanograms) undergoing
      adenoidectomy or adenotonsillectomy. All patients were operated by single
      experienced team using curettage technique. First tympanometry was done on the
      day before surgery. Tympanometry was repeated on the first-, third-, and seventh
      day after the operation. Patients are separated into two groups according to age
      as patients younger than 6 years (Group A) and patients older than 6 years (Group
      B). All data were separately evaluated for each ear using Jerger Classification.
      RESULTS: Of the 64 patients included in the study, 35 were male and 29 were
      female, and the average age was 91.01 +/- 37.4 (35-178) months. Pathological
      decreases in the middle ear pressures of at least one ear were determined in 48
      (75%) patients on the first postoperative day and in 10 (15.6%) patients on the
      third postoperative day. Middle ear pressures returned to preoperative values by
      the seventh postoperative day except in two patients. There were statistically
      significant differences (p<0.0001) among preoperative and first, third, and
      seventh postoperative day mean middle ear pressure. There were no statistically
      significant differences between Groups A and B in terms of tympanometry values of
      both ears obtained preoperatively and on the first, third, and seventh
      postoperative day. CONCLUSION: In our study, temporary eustachian dysfunction and
      aural fullness occur in the early period after adenoidectomy and/or
      adenotonsillectomy. This situation may be due to post-surgery clots and edema in
      nasopharynx. We consider that tubal orifice can be exposed to surgical trauma as
      adenoidectomy surgeries are done by curettage technique. There is a need for
      comparative studies using microdebrider or laser adenoidectomy accompanied by an
      endoscope.

PMID- 25766623
TI  - Near-total removal of facial nerve schwannomas: long-term outcomes.
AB  - OBJECTIVE: The study aimed to present long-term outcomes of near-total removal of
      facial nerve schwannomas (FNS) with good facial nerve function (HB Grade III or
      better). METHODS: We successfully performed near-total removal of FNS (tumor
      removal of 95% or greater) on 13 cases, and the remaining 6 cases who failed
      underwent total tumor removal and nerve grafting. Patients were divided into near
      total removal group and total removal group according to surgical approach, and
      they were followed up for 7.38 +/- 1.98 years (range, 5 to 11 years) and 6.66 +/-
      1.63 years (range, 5 to 9 years), respectively. RESULTS: 12 of 13 cases (92.3%)
      in the near-total removal group successfully maintained at least Grade III except
      one who recurred and underwent complete tumor removal and nerve grafting, and 10
      cases (76.9%) achieved Grade I or Grade II. 5 of 6 cases (83.3%) in the total
      removal group obtained Grade III, but none recovered to Grade I or II. Tumor
      growth was noted in only one case (7.7%) among the near-total removal group
      during the follow-up. CONCLUSIONS: Long-term outcomes of near-total removal of
      FNS were favorable, which may be a good choice for the old patients with good
      facial nerve function.

PMID- 25766624
TI  - Cardiovascular MR angiography in partial anomalous pulmonary venous connection.

PMID- 25766626
TI  - Innovative approaches to the design and synthesis of small molecule libraries.

PMID- 25766625
TI  - Transport of organic anions and cations in murine embryonic kidney development
      and in serially-reaggregated engineered kidneys.
AB  - Recent advances in renal tissue engineering have shown that dissociated, early
      renogenic tissue from the developing embryo can self-assemble into
      morphologically accurate kidney-like organs arranged around a central collecting
      duct tree. In order for such self-assembled kidneys to be useful therapeutically
      or as models for drug screening, it is necessary to demonstrate that they are
      functional. One of the main functional characteristics of mature kidneys is
      transport of organic anions and cations into and out of the proximal tubule.
      Here, we show that the transport function of embryonic kidneys allowed to develop
      in culture follows a developmental time-course that is comparable to embryonic
      kidney development in vivo. We also demonstrate that serially-reaggregated
      engineered kidneys can transport organic anions and cations through specific
      uptake and efflux channels. These results support the physiological relevance of
      kidneys grown in culture, a commonly used model for kidney development and
      research, and suggest that serially-reaggregated kidneys self-assembled from
      separated cells have some functional characteristics of intact kidneys. 

PMID- 25766627
TI  - Aminobenzoic acid incorporated octapeptides for cation transport.
AB  - Robust oligopeptides that mimic natural ion channels are attractive for use as
      molecular switches or model systems to study ion transport. Herein, we report
      octapeptides derived from aminobenzoic acid and l/d amino acids. Two of the
      alanine containing peptides were found to be most active and the peptide
      containing p-aminobenzoic acid was found to be most active (2.4 times its m
      analog). Experimental studies indicate the peptides do not transport halides and
      transport alkali metal ions. 

PMID- 25766628
TI  - Synthesis and antifungal activity of 5-iodo-1,4-disubstituted-1,2,3-triazole
      derivatives as pyruvate dehydrogenase complex E1 inhibitors.
AB  - To identify new antifungal lead compound based on inhibitors of pyruvate
      dehydrogenase complex E1, a series of 5-iodo-1,4-disubstituted-1,2,3-triazole
      derivatives 3 were prepared and evaluated for their Escherichia coli PDHc-E1
      inhibitory activity and antifungal activity. The in vitro bioassay for the PDHc
      E1 inhibition indicated all the compounds exhibited significant inhibition
      against E. coli PDHc-E1 (IC50<21MUM), special compound 3g showed the most potent
      inhibitory activity (IC50=4.21+/-0.11MUM) and was demonstrated to act as a
      competitive inhibitor of PDHc-E1. Meanwhile, inhibitor 3g exhibited very good
      enzyme-selective inhibition of PDHc-E1 between pig heart and E. coli. The assay
      of antifungal activity showed compounds 3e, 3g, and 3n exhibited fair to good
      activity against Rhizoctonia solani and Botrytis cinerea even at 12.5MUg/mL.
      Especially compound 3n (EC50=5.4MUg/mL; EC90=21.1MUg/mL) exhibited almost 5.50
      times inhibitory potency against B. cinerea than that of pyrimethanil
      (EC50=29.6MUg/mL; EC90=113.4MUg/mL). Therefore, in this study, compound 3n was
      found to be a novel lead compound for further optimization to find more potent
      antifungal compounds as microbial PDHc-E1 inhibitors.

PMID- 25766629
TI  - Development of 2-amino-5-phenylthiophene-3-carboxamide derivatives as novel
      inhibitors of Mycobacterium tuberculosis DNA GyrB domain.
AB  - DNA gyrase is the only type II topoisomerase in Mycobacterium tuberculosis (Mtb),
      unlike other bacteria and its absence in human being makes it a clinically
      validated target for developing anti-tubercular leads against Mtb. In the present
      study, our effort was to optimize and synthesize a series of compounds by a
      combination of molecular docking, and synthetic chemistry approach for better
      activity. A series of twenty eight substituted 2-amino-5-phenylthiophene-3
      carboxamide derivatives were designed based on our earlier reported Mtb GyrB
      inhibitor lead. Hit expansion of the previously identified lead by chemical
      synthesis led to improved inhibitor with an IC50 value of 0.86+/-0.81MUM against
      Mtb DNA gyrase supercoiling and Mycobacterium smegmatis GyrB IC50 of 1.35+/
      0.58MUM. Further a biophysical investigation using differential scanning
      fluorimetry experiments re-ascertained the affinity of these molecules towards
      the GyrB domain.

PMID- 25766630
TI  - A class of sulfonamide carbonic anhydrase inhibitors with neuropathic pain
      modulating effects.
AB  - A series of benzene sulfonamide carbonic anhydrase (CA, EC 4.2.1.1) inhibitors
      which incorporate lipophilic 4-alkoxy- and 4-aryloxy moieties, together with
      several derivatives of ethoxzolamide and sulfanilamide are reported. These
      derivatives were investigated as inhibitors of the metalloenzyme carbonic
      anhydrase (CA, EC 4.2.1.1) of which multiple isoforms are known, and some appear
      to be involved in pain. These sulfonamides showed modest inhibition against the
      cytosolic isoform CA I, but were generally effective, low nanomolar CA II, VII,
      IX and XII inhibitors. X-ray crystallographic data for the adduct of several such
      sulfonamides with CA II allowed us to rationalize the good inhibition data. In a
      mice model of neuropathic pain induced by oxaliplatin, one of the strong CA
      II/VII inhibitors reported here induced a long lasting pain relieving effect, a
      fact never observed earlier. This is the first report of rationally designed
      sulfonamide CA inhibitors with pain effective modulating effects. 

PMID- 25766631
TI  - Design, synthesis and biological evaluation of functionalized phthalimides: a new
      class of antimalarials and inhibitors of falcipain-2, a major hemoglobinase of
      malaria parasite.
AB  - Phthalimides functionalized with cyclic amines were synthesized, characterized
      and screened for their in vitro antimalarial efficacy against Plasmodium
      falciparum (Pf3D7). Of all the listed phthalimides evaluated, 14 and 24 were
      identified as potent antimalarial agents as advocated by assessment of their
      ability to inhibit [(3)H] hypoxanthine incorporation in the nucleic acid of
      parasites. In addition, phthalimides 14 and 24 were incubated for 60 and 90h and
      an enhanced antimalarial effect was noticed with increase in time to great
      extent. A reduction in IC50 values was observed with increase in exposure time of
      the parasite to the compounds. A symmetric phthalimide, 24 possessing piperazine
      as linker unit was identified as the most potent antimalarial agent with IC50
      values of 5.97+/-0.78, 2.0+/-1.09 and 1.1+/-0.75MUM on incubation period of 42,
      60 and 90h, respectively. The abnormal morphologies such as delay in
      developmental stages, growth arrest and condensed nuclei of parasite were
      observed with the aid of microscopic studies upon exposure with 14 and 24. The
      evaluation of 14 and 24 against chloroquine resistant strain, (Pf7GB) of P.
      falciparum afforded IC50 values, 13.29+/-1.20 and 7.21+/-0.98MUM, respectively.
      The combination of 24 with artemisinin (ART) showed enhanced killing of parasite
      against Pf3D7. Further, all phthalimides were evaluated for their activity
      against falcipain-2 (FP2), a major hemoglobinase of malarial parasite. The
      enzymatic assay afforded 6 as most active member against FP2. To the best of our
      knowledge this is the initial study represents phthalimide protected amino acids
      functionalized with cyclic amines as potent antimalarial agents.

PMID- 25766632
TI  - Synthesis and biological evaluation of spirocyclic antagonists of CCR2 (chemokine
      CC receptor subtype 2).
AB  - Activation of chemokine CC receptors subtype 2 (CCR2) plays an important role in
      chronic inflammatory processes such as atherosclerosis, multiple sclerosis and
      rheumatoid arthritis. A diverse set of spirocyclic butanamides 4 (N-benzyl-4-(3,4
      dihydrospiro[[2]benzopyran-1,4'-piperidin]-1'-yl)butanamides) was prepared by
      different combination of spirocyclic piperidines 8 (3,4
      dihydrospiro[[2]benzopyran-1,4'-piperidines]) and gamma-halobutanamides 11. A key
      step in the synthesis of spirocyclic piperidines 8 was an Oxa-Pictet-Spengler
      reaction of beta-phenylethanols 5 with piperidone acetal 6. The substituted gamma
      hydroxybutanamides 11c-e were prepared by hydroxyethylation of methyl acetates 13
      with ethylene sulfate giving the gamma-lactones 14c and 14e. Aminolysis of the
      gamma-lactones 14c and 14e with benzylamines provided the gamma
      hydroxybutanamides 15c-e, which were converted into the bromides 11c-e by an
      Appel reaction using polymer-bound PPh3. In radioligand binding assays the
      spirocyclic butanamides 4 did not displace the iodinated radioligand (125)I-CCL2
      from the human CCR2. However, in the Ca(2+)-flux assay using human CCR2 strong
      antagonistic activity of butanamides 4 was detected. Analysis of the IC50-values
      led to clear relationships between the structure and the inhibition of the Ca(2+)
      flux. 4g (4-(3,4-dihydrospiro[[2]benzopyran-1,4'-piperidin]-1'-yl)-N-[3,5
      bis(trifluoromethylbenzyl)]-2-(4-fluorophenyl)butanamide) and 4o (N-[3,5
      bis(trifluoromethyl)benzyl]-2-cyclopropyl-4-(3,4-dihydrospiro[[2]benzopyran-1,4'
      piperidin]-1'-yl)butanamide) represent the most potent CCR2 antagonists with IC50
      values of 89 and 17nM, respectively. Micromolar activities were found in the beta
      arrestin recruitment assay with murine CCR2, but the structure-activity
      relationships detected in the Ca(2+)-flux assay were confirmed. 

PMID- 25766634
TI  - Coronary microvascular dysfunction correlates with the new onset of cardiac
      allograft vasculopathy in heart transplant patients with normal coronary
      angiography.
AB  - Coronary microvascular dysfunction is emerging as a strong predictor of outcome
      in heart transplantation (HT). We assessed the validity of microvascular
      dysfunction, defined by means of a reduced coronary flow reserve (CFR), as a
      factor associated with new onset epicardial cardiac allograft vasculopathy (CAV)
      or death. We studied 105 patients at 4 +/- 1 years post-HT with a normal coronary
      angiography (CA). New onset CAV was assessed by CA. CFR was assessed in the left
      anterior descending (LAD) coronary artery by transthoracic Doppler
      echocardiography and calculated as the ratio of hyperaemic to basal blood flow
      velocity. A CFR <= 2.5 was considered abnormal. Epicardial CAV onset or death was
      assessed during a follow-up of 10 years. New onset CAV was diagnosed in 30
      patients (28.6%) (Group A), and the CA was normal in the remaining 75 patients
      (71.4%) (Group B). Group A had reduced CFR compared with group B (2.4 +/- 0.6 vs.
      3.2 +/- 0.7, p < 0.0001). A CFR <= 2.5 was independently associated with a higher
      probability of new onset CAV (p < 0.0001) and a higher probability of death,
      regardless of CAV onset (p < 0.01). Microvascular dysfunction is independently
      associated with the onset of epicardial CAV, and associated with a higher risk of
      death, regardless of CAV onset. 

PMID- 25766635
TI  - Surface modification-induced phase transformation of hexagonal close-packed gold
      square sheets.
AB  - Conventionally, the phase transformation of inorganic nanocrystals is realized
      under extreme conditions (for example, high temperature or high pressure). Here
      we report the complete phase transformation of Au square sheets (AuSSs) from
      hexagonal close-packed (hcp) to face-centered cubic (fcc) structures at ambient
      conditions via surface ligand exchange, resulting in the formation of (100)f
      oriented fcc AuSSs. Importantly, the phase transformation can also be realized
      through the coating of a thin metal film (for example, Ag) on hcp AuSSs.
      Depending on the surfactants used during the metal coating process, two
      transformation pathways are observed, leading to the formation of (100)f-oriented
      fcc Au@Ag core-shell square sheets and (110)h/(101)f-oriented hcp/fcc mixed Au@Ag
      nanosheets. Furthermore, monochromated electron energy loss spectroscopy reveals
      the strong surface plasmon resonance absorption of fcc AuSS and Au@Ag square
      sheet in the infrared region. Our findings may offer a new route for the crystal
      phase and shape-controlled synthesis of inorganic nanocrystals. 

PMID- 25766633
TI  - Dual inhibition of allosteric mitogen-activated protein kinase (MEK) and
      phosphatidylinositol 3-kinase (PI3K) oncogenic targets with a bifunctional
      inhibitor.
AB  - The MAP kinase (Ras/MEK/ERK) and PI3K/Akt/mTOR oncogenic signaling pathways are
      central regulators of KRAS-mediated transformation. Molecular reciprocity between
      the Ras/MEK/ERK and PI3K/Akt/mTOR pathways provides cancer cells with the ability
      to evade treatment when targeting only one pathway with monotherapy. Multi-kinase
      targeting was explored through the development of a single bivalent chemical
      entity by covalent linking of high-affinity MEK and PI3K inhibitors. A prototype
      dual-acting agent (compound 8) designed using the PI3K inhibitor ZSTK474 and the
      Raf/MEK inhibitor RO5126766 as scaffolds displayed high in vitro inhibition of
      both PI3K (IC50=172nM) and MEK1 (IC50=473nM). Additionally, compound 8
      demonstrated significant modulation of MEK and PI3K signaling pathway activity in
      human A549 human lung adenocarcinoma cells and pancreatic cancer cells (PANC-1)
      and also decreased cellular viability in these two cell lines.

PMID- 25766636
TI  - Types of homes and ways of life: a territorial analysis of the environmental
      determinants that factor into the proliferation of malaria vectors in the rural
      region of Allada in Benin.
AB  - INTRODUCTION: Anthropogenic factors, as well as environmental factors, can
      explain fine-scale spatial differences in vector densities and seasonal
      variations in malaria. In this pilot study, numbers of Anopheles gambiae were
      quantified in concessions in a rural area of southern Benin, West Africa, in
      order to establish whether vector number and human factors, such as habitat and
      living practices, are related. METHODS: The courtyard homes of 64 concessions
      (houses and private yards) were systematically and similarly photographed.
      Predefined features in the photographed items were extracted by applying an
      analysis grid that listed vector resting sites or potential breeding sites and
      also more general information about the building materials used. These data were
      analysed with respect to entomological data (number of mosquitoes caught per
      night) using the Kruskal-Wallis test, Pearson correlation coefficients, and
      analysis of covariance (ANCOVA). RESULTS: Three recurrent habitat/household types
      and living practices were identified that corresponded to different standards of
      living. These were related to the average number of mosquitoes captured per
      night: type I=0.88 anopheles/night; type II=0.85; and type III 0.55, but this was
      not statistically significant (Kruskal-Wallis test; p=0.41). There were no
      significant relationships between the number of potential breeding sites and
      number of mosquitoes caught (Pearson's correlation coefficient=-0.09, p=0.53).
      ANCOVA analysis of building materials and numbers of openings did not explain
      variation in the number of mosquitoes caught. CONCLUSIONS: Three dwelling types
      were identified by using predetermined socio-environmental characteristics but
      there was no association found in this study between vector number and habitat
      characteristics as was suspected.

PMID- 25766637
TI  - Pressure resistance of cold-shocked Escherichia coli O157:H7 in ground beef, beef
      gravy and peptone water.
AB  - AIMS: (i) To study the effects of cold shock on Escherichia coli O157:H7 cells.
      (ii) To determine if cold-shocked E. coli O157:H7 cells at stationary and
      exponential phases are more pressure-resistant than their non-cold-shocked
      counterparts. (iii) To investigate the baro-protective role of growth media (0.1%
      peptone water, beef gravy and ground beef). METHODS AND RESULTS: Quantitative
      estimates of lethality and sublethal injury were made using the differential
      plating method. There were no significant differences (P > 0.05) in the number of
      cells killed; cold-shocked or non-cold-shocked. Cells grown in ground beef
      (stationary and exponential phases) experienced lowest death compared with
      peptone water and beef gravy. Cold-shock treatment increased the sublethal injury
      to cells cultured in peptone water (stationary and exponential phases) and ground
      beef (exponential phase), but decreased the sublethal injury to cells in beef
      gravy (stationary phase). CONCLUSIONS: Cold shock did not confer greater
      resistance to stationary or exponential phase cells pressurized in peptone water,
      beef gravy or ground beef. Ground beef had the greatest baro-protective effect.
      SIGNIFICANCE AND IMPACT OF THE STUDY: Real food systems should be used in
      establishing food safety parameters for high-pressure treatments; micro-organisms
      are less resistant in model food systems, the use of which may underestimate the
      organisms' resistance.

PMID- 25766638
TI  - viral silencing suppressors: Tools forged to fine-tune host-pathogen coexistence.
AB  - RNA silencing is a homology-dependent gene inactivation mechanism that regulates
      a wide range of biological processes including antiviral defense. To deal with
      host antiviral responses viruses evolved mechanisms to avoid or counteract this,
      most notably through expression of viral suppressors of RNA silencing. Besides
      working as silencing suppressors, these proteins may also fulfill other functions
      during infection. In many cases the interplay between the suppressor function and
      other "unrelated" functions remains elusive. We will present host factors
      implicated in antiviral pathways and summarize the current status of knowledge
      about the diverse viral suppressors' strategies acting at various steps of
      antiviral silencing in plants. Besides, we will consider the multi-functionality
      of these versatile proteins and related biochemical processes in which they may
      be involved in fine-tuning the plant-virus interaction. Finally, we will present
      the current applications and discuss perspectives of the use of these proteins in
      molecular biology and biotechnology. 

PMID- 25766639
TI  - Large dsDNA chloroviruses encode diverse membrane transport proteins.
AB  - Many large DNA viruses that infect certain isolates of chlorella-like green algae
      (chloroviruses) are unusual because they often encode a diverse set of membrane
      transport proteins, including functional K(+) channels and aquaglyceroporins as
      well as K(+) transporters and calcium transporting ATPases. Some chloroviruses
      also encode putative ligand-gated-like channel proteins. No one protein is
      present in all of the chloroviruses that have been sequenced, but the K(+)
      channel is the most common as only two chloroviruses have been isolated that lack
      this complete protein. This review describes the properties of these membrane
      transporting proteins and suggests possible physiological functions and
      evolutionary histories for some of them. 

PMID- 25766641
TI  - Event-Related Synchronization and Desynchronization of High-Frequency
      Electroencephalographic Activity during a Visual Go/No-Go Paradigm.
AB  - OBJECTIVE: High-frequency electroencephalography (EEG) activity has been observed
      in association with cognitive processing, including stimulus perception,
      consciousness and selective attention, in humans. The aim of this study was to
      compare visual-motor integrated processing between execution and inhibition of a
      motor response using event-related synchronization (ERS) and desynchronization
      (ERD) in the 15- to 80-Hz range and to investigate a relationship between event
      related potentials (ERPs) and ERS/ERD in 10 normal young subjects. METHODS: EEGs
      were recorded from 21 scalp sites during a visual go/no-go paradigm. For ERPs, 40
      artifact-free trials were averaged off-line referenced to linked ear lobes. In
      the beta and gamma bands, ERS and ERD were calculated by time-frequency analysis.
      RESULTS: Go N2 and no-go N2 were elicited 200-250 ms after stimuli, and their
      distributions were predominant at Fz. Go P3 was predominantly elicited 340-360 ms
      after stimuli at Pz, whereas no-go P3 was predominantly elicited 360-380 ms after
      stimuli at Cz. ERD of the beta band at Fz and Cz during 300-600 ms showed in the
      go condition, whereas ERD showed between 39 and 42 Hz at F3 in the no-go
      condition. CONCLUSION: Oscillatory cortical response-related beta and gamma
      activities differ between the processing of execution and inhibition in motor
      responses. beta ERDs in the sensorimotor areas with go stimuli may be related to
      motor responses, and gamma ERDs in the left frontal area with no-go stimuli may
      be involved in the processing of inhibition of motor responses. (c) 2015 S.
      Karger AG, Basel.

PMID- 25766640
TI  - Anti-tumour necrosis factor treatment increases circulating T helper type 17
      cells similarly in different types of inflammatory arthritis.
AB  - We investigated changes in circulating T helper type 17 (Th17) cells following
      anti-tumour necrosis factor (TNF) in rheumatoid arthritis (RA), ankylosing
      spondylitis (AS) and psoriatic arthritis (PsA) patients. Peripheral blood
      mononuclear cells (PBMC) were isolated from 25 RA, 15 AS and eight PsA patients
      at baseline 4 and 12 weeks after treatment, and Th17 cell frequencies were
      analysed using interleukin (IL)-17 enzyme-linked immunospot (ELISPOT) and flow
      cytometry. A significant increase in IL-17-producing cells was observed by
      ELISPOT in RA and AS patients at 12 weeks. Flow cytometry confirmed significant
      increases in CD4(+) IL-17(+) cells at 12 weeks in RA and AS and 4 weeks in PsA
      patients. Anti-TNF treatment increases circulating Th17 cells in three different
      diseases. 

PMID- 25766642
TI  - Aberrant C-terminal domain of polymerase eta targets the functional enzyme to the
      proteosomal degradation pathway.
AB  - Xeroderma pigmentosum variant (XP-V) is a rare genetic disease, characterized by
      sunlight sensitivity and predisposition to cutaneous malignancies. XP-V is caused
      by a deficiency in DNA polymerase eta (Poleta) that plays a pivotal role in
      translesion synthesis by bypassing UV-induced pyrimidine dimers. Previously we
      identified a new Poleta variant containing two missense mutations, one mutation
      within the bipartite NLS (T692A) and a second mutation on the stop codon (X714W)
      leading to a longer protein with an extra 8 amino acids (721 instead of 713 AA).
      First biochemical analysis revealed that this Poleta missense variant was barely
      detectable by western blot. As this mutant is extremely unstable and is nearly
      undetectable, a definitive measure of its functional deficit in cells has not
      been explored. Here we report the molecular and cellular characterization of this
      missense variant. In cell free extracts, the extra 8 amino acids in the C
      terminal of Poleta(721) only slightly reduce the bypass efficiency through CPD
      lesions. In vivo, Poleta(721) accumulates in replication factories and interacts
      with mUb-PCNA albeit at lower level than Poleta(wt). XP-V cells overexpressing
      Poleta(721) were only slightly UV-sensitive. Altogether, our data strongly
      suggest that Poleta(721) is functional and that the patient displays a XP-V
      phenotype because the mutant protein is excessively unstable. We then
      investigated the molecular mechanisms involved in this excessive proteolysis. We
      showed that Poleta(721) is degraded by the proteasome in an ubiquitin-dependent
      manner and that this proteolysis is independent of the E3 ligases, CRL4(cdt2) and
      Pirh2, reported to promote Poleta degradation. We then demonstrated that the
      extra 8 amino acids of Poleta(721) do not act as a degron but rather induce a
      conformational change of the Poleta C-terminus exposing its bipartite NLS as well
      as a sequence close to its UBZ to the ubiquitin/proteasome system. Interestingly
      we showed that the clinically approved proteasome inhibitor, Bortezomib restores
      the levels of Poleta(721) suggesting that this might be a therapeutic approach to
      preventing tumor development in certain XP-V patients harboring missense
      mutations. 

PMID- 25766643
TI  - The steady-state level and stability of TLS polymerase eta are cell cycle
      dependent in the yeast S. cerevisiae.
AB  - Polymerase eta (Pol eta) is a ubiquitous translesion DNA polymerase that is
      capable of bypassing UV-induced pyrimidine dimers in an error-free manner.
      However, this specialized polymerase is error prone when synthesizing through an
      undamaged DNA template. In Saccharomyces cerevisiae, both depletion and
      overproduction of Pol eta result in mutator phenotypes. Therefore, regulation of
      the cellular abundance of this enzyme is of particular interest. However, based
      on the investigation of variously tagged forms of Pol eta, mutually contradictory
      conclusions have been reached regarding the stability of this polymerase in
      yeast. Here, we optimized a protocol for the detection of untagged yeast Pol eta
      and established that the half-life of the native enzyme is 80 +/- 14 min in
      asynchronously growing cultures. Experiments with synchronized cells indicated
      that the cellular abundance of this translesion polymerase changes throughout the
      cell cycle. Accordingly, we show that the stability of Pol eta, but not its mRNA
      level, is cell cycle stage dependent. The half-life of the polymerase is more
      than fourfold shorter in G1-arrested cells than in those at G2/M. Our results, in
      concert with previous data for Rev1, indicate that cell cycle regulation is a
      general property of Y family TLS polymerases in S. cerevisiae.

PMID- 25766644
TI  - Phloroglucinol enhances the repair of UVB radiation-induced DNA damage via
      promotion of the nucleotide excision repair system in vitro and in vivo.
AB  - Exposure to solar UVB radiation can lead to the formation of DNA lesions such as
      cyclobutane pyrimidine dimers (CPDs). Nucleotide excision repair (NER) is
      critical for the repair of CPDs induced by UV radiation. The purpose of this
      study was to investigate the ability of phloroglucinol to protect against the
      formation of UVB-induced CPDs in vitro and in vivo. Exposure to UVB radiation
      increased the number of CPDs in both HaCaT keratinocytes and mouse skin; however,
      these increases were reduced by treatment with phloroglucinol. Expression levels
      of xeroderma pigmentosum complementation group C (XPC) and excision repair cross
      complementation 1 (ERCC1), which are essential components of the NER pathway,
      were reduced following UVB exposure, although phloroglucinol treatment recovered
      these levels in both HaCaT keratinocytes and mouse skin. Phloroglucinol also
      inhibited UVB-induced reductions in binding of the transcription factors
      specificity protein 1 to the XPC promoter. These results demonstrate that
      phloroglucinol can protect cells against UVB-induced DNA damage by inducing NER. 

PMID- 25766645
TI  - Zincation of 4,4-dimethyloxazoline using TMPZnCl.LiCl. A new preparation of 2
      aryloxazolines.
AB  - The metalation of 4,4-dimethyloxazoline using TMPZnCl.LiCl provides a stable 2
      zincated oxazolinyl reagent which readily undergoes palladium-catalyzed Negishi
      cross-couplings allowing a new access to 2-aryloxazolines. Cu-mediated acylation
      and allylation reactions also proceed in good yields. 

PMID- 25766647
TI  - A plasmonic nanosensor for lipase activity based on enzyme-controlled gold
      nanoparticles growth in situ.
AB  - A plasmonic nanosensor for lipase activity was developed based on one-pot
      nanoparticle growth. Tween 80 was selected not only as the substrate for lipase
      recognition but also as the reducing and stabilizing agent for the sensor
      fabrication. The different molecular groups in Tween 80 could have different
      roles in the fabrication procedure; the H2O2 produced by the autoxidation of the
      ethylene oxide subunits in Tween 80 could reduce the AuCl4(-) ions to Au atoms,
      meanwhile, the lipase could hydrolyze its carboxyl ester bond, which could, in
      turn, control the rate of nucleation of the gold nanoparticles (AuNPs) and tailor
      the localized surface plasmon resonance (LSPR) of the AuNP transducers. The color
      changes, which depend on the absence or presence of the lipase, could be used to
      sense the lipase activity. A linear response ranging from 0.025 to 4 mg mL(-1)
      and a detection limit of the lipase as low as 3.47 MUg mL(-1) were achieved. This
      strategy circumvents the problems encountered by general enzyme assays that
      require sophisticated instruments and complicated assembling steps. The
      methodology can benefit the assays of heterogeneous-catalyzed enzymes. 

PMID- 25766648
TI  - Microencapsulation of metal-based phase change material for high-temperature
      thermal energy storage.
AB  - Latent heat storage using alloys as phase change materials (PCMs) is an
      attractive option for high-temperature thermal energy storage. Encapsulation of
      these PCMs is essential for their successful use. However, so far, technology for
      producing microencapsulated PCMs (MEPCMs) that can be used above 500 degrees C
      has not been established. Therefore, in this study, we developed Al-Si alloy
      microsphere MEPCMs covered by alpha-Al2O3 shells. The MEPCM was prepared in two
      steps: (1) the formation of an AlOOH shell on the PCM particles using a boehmite
      treatment, and (2) heat-oxidation treatment in an O2 atmosphere to form a stable
      alpha-Al2O3 shell. The MEPCM presented a melting point of 573 degrees C and
      latent heat of 247 J g(-1). The cycling performance showed good durability. These
      results indicated the possibility of using MEPCM at high temperatures. The MEPCM
      developed in this study has great promise in future energy and chemical
      processes, such as exergy recuperation and process intensification.

PMID- 25766649
TI  - Interactions between Neutrophils and Leishmania braziliensis Amastigotes
      Facilitate Cell Activation and Parasite Clearance.
AB  - Leishmania braziliensis and Leishmania amazonensis are both causative agents of
      cutaneous leishmaniasis in South America. However, patient prognosis and the host
      immune response differ considerably depending on the infecting parasite species.
      The mechanisms underlying these differences appear to be multifactorial, with
      both host and parasite components contributing to disease outcome. As neutrophils
      are a prominent component of the inflammatory infiltrate in chronic cutaneous,
      diffuse cutaneous and mucocutaneous lesions, we examined neutrophil activation
      and microbicidal activity against amastigotes of L. amazonensis and L.
      braziliensis. We found that murine neutrophils internalized L. braziliensis
      amastigotes with greater efficiency than did L. amazonensis amastigotes.
      Additionally, L. braziliensis infection was a potent trigger for neutrophil
      activation, oxidative burst, degranulation and the production of interleukin (IL)
      22 and IL-10, while L. amazonensis amastigotes poorly induced these responses.
      Finally, neutrophils were able to kill L. braziliensis amastigotes, especially
      when cells were activated with phorbol myristate acetate. L. amazonensis
      amastigotes, however, were highly resistant to neutrophil microbicidal
      mechanisms. This study reveals, for the first time, differential neutrophil
      responsiveness to distinct species of Leishmania amastigotes and highlights the
      complexity of neutrophil-amastigote interactions during chronic leishmaniasis.

PMID- 25766650
TI  - Changes in the Lemann Index Values During the First Years of Crohn's Disease.
AB  - BACKGROUND & AIMS: Stricturing or penetrating lesions develop over time in most
      patients with Crohn's disease. The Lemann Index indicates the degree of digestive
      damage at a given time in an individual. We tracked changes in Lemann Index
      scores in an inception cohort of patients and looked for factors associated with
      digestive damage. METHODS: We studied 221 patients diagnosed with Crohn's disease
      from 2004 through 2011 who received 2 or 3 serial morphologic evaluations over a
      period of 2 to 10 years. We collected cross-sectional images and had them
      reviewed by a gastroenterologist and a radiologist; Lemann index scores were
      calculated. A value of 2 was chosen as the cut-off value for substantial
      transparietal damage. Factors associated with a score greater than 2 at the last
      evaluation and progression of index scores were identified using univariate
      analysis and logistic regression analyses. RESULTS: The median index Lemann Index
      scores were 2.3 (interquartile range [IQR], 1.2-3.9) at first evaluation, 3.5
      (IQR, 1.2-8.6) at 2 to 5 years after diagnosis, and 8.3 (IQR, 1.2-12.1) at 5 to
      10 years after diagnosis. Index scores increased significantly at each stage
      compared with initial or previous values (P < .0001). After 73 months (IQR, 51-96
      mo) of follow-up evaluation, 138 patients had a Lemann Index score greater than
      2.0. The only early factor that predicted later damage was the first index value.
      Intestinal resection, time, and the percentage of time elapsed with a clinically
      active disease were associated with progressing damage. CONCLUSIONS: Based on an
      analysis of patients with Crohn's disease using the Lemann Index, nearly two
      thirds had substantial mucosal damage 2 to 10 years after diagnosis. High Lemann
      index scores at the first evaluation, time, persistent clinical activity, and
      intestinal resection are associated with damage.

PMID- 25766651
TI  - A Markov Decision Model to Guide Treatment of Recurrent Colonic Diverticulitis.
AB  - BACKGROUND & AIMS: Although colonic diverticulitis is a common disorder, there is
      no clear treatment strategy for patients with recurrent episodes of
      diverticulitis. We investigated whether colonic resection or conservative or
      medical treatments have the greatest effects on quality-adjusted life-years
      (QALYs). METHODS: A Markov model simulating patients with 2 episodes of non
      surgically treated diverticulitis was used to simulate all relevant outcomes of
      each treatment strategy. A 1-year cycle length with 10-year follow-up period was
      used to allow for chance of recurrent diverticulitis. Primary outcome was QALYs
      gained from each strategy. Factors considered were morbidity, mortality, chance
      of colostomy formation, risk of recurrence, and persistence of abdominal pain.
      The probabilities of clinical events were determined by using the best available
      published data. RESULTS: A strategy in which colonic resection was performed
      after 2 episodes of diverticulitis was associated with the lowest quality
      adjusted survival (a gain of 8.66 QALYs) and highest chance of stoma formation
      (1.1%) but the lowest chance of a mild (3.5%) or severe (1.1%) recurrence. The
      strategies of colonic resection or conservative or medical treatment after the
      third episode of diverticulitis were comparable in terms of quality-adjusted
      survival, providing 8.78, 8.76, and 8.74 QALYs, respectively. Probabilistic
      sensitivity analysis did not change these results. Persistent abdominal
      complaints were lowest in the medical treatment strategy. CONCLUSIONS: Elective
      surgery after 2 episodes of diverticulitis should be questioned in terms of
      QALYs. After the third episode of diverticulitis, surgical or conservative or
      medical treatments provide similar QALYs, but rates of abdominal symptoms are
      lower with the medical treatment strategy. This Markov decision model has
      limitations when the individual patient and physician face a complex decision
      weighing early and long-term risks and benefits of elective surgery or
      conservative management.

PMID- 25766652
TI  - Performance and characteristics of the Newborn Hearing Screening Programme in
      England: The first seven years.
AB  - OBJECTIVE: To assess the performance of the universal newborn hearing screen in
      England. DESIGN: Retrospective analysis of population screening records. STUDY
      SAMPLE: A total of 4 645 823 children born 1 April 2004 to 31 March 2013.
      RESULTS: 97.5% of the eligible population complete screening by 4/5 weeks of age
      and 98.9% complete screening by three months of age. The refer rate for the 12/13
      birth cohort is 2.6%. The percentage of screen positive (i.e. referred) babies
      commencing follow up by four weeks of age and six months of age is 82.5% and
      95.8% respectively. The yield of bilateral PCHL from the screen is around 1/1000.
      For bilateral PCHL in the 12/13 birth cohort the median age is nine days at
      screen completion, 30 days at entry into follow up, 49 days at confirmation, 50
      days at referral to early intervention, and 82 days at hearing-aid fitting.
      CONCLUSION: The performance of the newborn hearing screening programme has
      improved continuously. The yield of bilateral PCHL from the screen is about
      1/1000 as expected. The age of identification and management is well within the
      first six months of life, although there remains scope for further improvement
      with respect to timely entry into follow up.

PMID- 25766653
TI  - Structure and composition of mixed micelles of polymerized and monomeric
      surfactants.
AB  - Micelle structure and composition has been determined by small-angle neutron
      scattering for mixed micellar solutions of in situ polymerized omega
      methacryloyloxyundecyl-trimethylammonium bromide (MUTAB) in equilibrium with its
      monomeric form at various concentrations, as well as in mixtures with a
      fluorinated cationic surfactant, heptadecafluorodecylpyridinium chloride
      (HFDePC), and the non-ionic surfactant, C12E7. Whereas polymerized MUTAB is
      immiscible with HFDePC and forms two populations of distinct spheroidal micelles,
      it mixes with C12E7 in all proportions and forms a single average micelle
      structure depending on composition. These results allow us to explain the origin
      of the previously reported formation of mixed worm-like micelles of polymerized
      and monomeric MUTAB that coexist with globular monomeric MUTAB micelles as a
      consequence of the unfavourable electrostatic interactions that accompany the
      uncoiling of polymerized MUTAB chains in unimer micelles when swollen by
      monomeric cationic surfactants. 

PMID- 25766654
TI  - Coalescence behavior of oil droplets coated in irreversibly-adsorbed surfactant
      layers.
AB  - Coalescence between oil caps with irreversibly adsorbed layers of nonionic
      surfactant is characterized in deionized water and electrolyte solution. The
      coalescence is characterized using a modified capillary tensiometer allowing for
      accurate measurement of the coalescence time. Results suggest two types of
      coalescence behavior, fast coalescence at low surface coverages that are
      independent of ionic strength and slow coalescence at high coverage. These slow
      coalescence events (orders of magnitude slower) are argued to be due to electric
      double layer forces or more complicated stabilization mechanisms arising from
      interfacial deformation and surface forces. A simple film drainage model is used
      in combination with measured values for interfacial properties to quantify the
      interaction potential between the two interfaces. Since this approach allows the
      two caps to have the same history, interfacial coverage and curvature, the
      results offer a tool to better understand a mechanism that is important to
      emulsion stability. 

PMID- 25766655
TI  - Disability levels and correlates among older mobile home dwellers, an NHATS
      analysis.
AB  - BACKGROUND: Although remarkably understudied, manufactured or mobile homes are
      the housing choice for nearly 20 million Americans and little is known about the
      health of older persons living in mobile homes. OBJECTIVE: We sought to
      investigate disability levels and other health correlates among older adults
      living in mobile or manufactured homes compared to their counterparts living in
      other types of homes. METHODS: We sampled non-institutional adults aged 65 years
      or older (n = 7609), of whom 344 lived in mobile homes, from the 2011 National
      Health and Aging Trends Study (NHATS). RESULTS: Respondents living in mobile
      homes (average age = 75.1 years; SD = 0.5) had lower education and income and
      medical insurance than older adults living in other types of community residence
      (average age = 77.5 years; SD = 0.2). They were more likely to smoke, have lung
      and heart disease, and report fair or poor general health status. Mobile home
      dwellers reported more difficulty or inability in performing the following
      activities of daily living when compared to their counterparts: stooping and
      kneeling (64.9% vs 60.8%, p = 0.007), walking 6 blocks (46.5% vs 41.5%, p =
      0.001), walking 3 blocks (37.7% vs 33.5%, p = 0.002), and climbing up to 20
      stairs (39.2% vs 34.8%, p = 0.02). Among those reporting disability, mobile home
      dwellers had fewer bathroom safety modifications. CONCLUSION: There is higher
      prevalence of chronic conditions, functional and cognitive impairment in older
      mobile home dwellers compared to older adults living in other types of housing.

PMID- 25766656
TI  - Bavachalcone-induced manganese superoxide dismutase expression through the AMP
      activated protein kinase pathway in human endothelial cells.
AB  - Mitochondrial oxidative stress has been suggested as a major etiological factor
      in cardiovascular diseases. Manganese superoxide dismutase (MnSOD) is an
      essential antioxidant mitochondrial enzyme. Although polyphenols can induce MnSOD
      expression, their mechanism of action remains unclear. We examined the effect of
      bavachalcone, a bioactive compound isolated from Psoralea corylifolia, on MnSOD
      protein expression and explored whether this effect is mediated through the AMP
      activated protein kinase (AMPK) signaling pathway. Our data showed that
      bavachalcone enhanced the luciferase activity of the MnSOD promoter and increased
      MnSOD mRNA and protein expressions. Moreover, bavachalcone suppressed the
      mitochondrial superoxide production in endothelial cells. Conversely,
      bavachalcone stimulated liver kinase B1 and AMPKalpha phosphorylation. mRNA
      interference by using short hairpin RNA (shRNA) of AMPK inhibited bavachalcone
      induced MnSOD expression. A-769662, an AMPK activator, also stimulated AMPK
      activity and increased MnSOD expression. Furthermore, AMPK knockdown by shRNA
      AMPK reversed the inhibitory effects of bavachalcone on mitochondrial superoxide
      production in endothelial cells. These findings indicate that bavachalcone can
      protect the endothelial function by increasing AMPK activity and MnSOD expression
      and reducing mitochondrial oxidative stress. .

PMID- 25766657
TI  - Synchronous small intestinal and appendiceal neuroendocrine tumours: a rare case.

PMID- 25766658
TI  - Nuclear factor of activated T cells in cancer development and treatment.
AB  - Since nuclear factor of activated T cells (NFAT) was first identified as a
      transcription factor in T cells, various NFAT isoforms have been discovered and
      investigated. Accumulating studies have suggested that NFATs are involved in many
      aspects of cancer, including carcinogenesis, cancer cell proliferation,
      metastasis, drug resistance and tumor microenvironment. Different NFAT isoforms
      have distinct functions in different cancers. The exact function of NFAT in
      cancer or the tumor microenvironment is context dependent. In this review, we
      summarize our current knowledge of NFAT regulation and function in cancer
      development and treatment. NFATs have emerged as a potential target for cancer
      prevention and therapy. 

PMID- 25766660
TI  - Resection of Borderline Resectable and Locally Advanced Pancreatic
      Adenocarcinomas after Neoadjuvant Chemotherapy.
AB  - OBJECTIVE: To report the outcomes of surgical resection of borderline resectable
      (BL) and locally advanced (LA) 'unresectable' pancreatic cancer after neoadjuvant
      chemotherapy. METHODS: A review of a prospectively maintained database for
      pancreatic resections was undertaken to identify patients undergoing resection
      for BL and LA pancreatic cancer after neoadjuvant chemotherapy between January
      2007 and December 2012. Clinicopathological, surgical and survival outcomes were
      analyzed. RESULTS: A total of 45 patients with LA (n = 34) or BL cancer (n = 11)
      underwent surgery after a mean (+/- SD) of 7 +/- 4 preoperative chemotherapy
      cycles. Ninety-day mortality was 6.7%, and overall morbidity was 33.3%. An R0
      resection was achieved in 34 patients, and 4 patients showed a complete
      pathological response. Overall median postoperative survival was 17 months (21
      after the start of neoadjuvant treatment). Overall and disease-free survival was
      74.9 and 43.6% at 1 year and 21.2 and 10.3% at 3 years, respectively. In BL
      cancer patients, the 3-year survival was significantly higher compared to that of
      LA cancer patients (p = 0.02). CONCLUSIONS: Curative intent resection in BL and
      LA cancer patients after neoadjuvant chemotherapy can be achieved with reasonable
      mortality and morbidity and an encouraging 3-year survival. After neoadjuvant
      therapy, resection provides a better overall survival for BL compared to LA
      cancer patients.

PMID- 25766661
TI  - Interobserver agreement and accuracy of non-invasive diagnosis of endometriosis
      by transvaginal sonography.
AB  - OBJECTIVES: To evaluate interobserver agreement and accuracy of transvaginal
      sonography (TVS) in diagnosing deep infiltrating endometriosis (DIE) and
      endometriomas. METHODS: A total of 67 consecutive patients referred to a pelvic
      pain clinic and scheduled for laparoscopy were enrolled in the study between
      January 2013 and January 2014. Patients were independently examined prospectively
      by two experienced sonographers (Observers A and B) who were blinded to the
      other's results. For the two observers, Gwet's first-order agreement coefficient
      (Gwet's AC1) was used to calculate interobserver agreement and diagnostic
      accuracy, as well as sensitivity, specificity, positive (PPV) and negative (NPV)
      predictive values using TVS, as compared to laparoscopy, for diagnosing DIE and
      endometriomas. RESULTS: Among the 67 patients enrolled, 65 were analyzed. For the
      diagnosis of DIE and endometriomas by TVS, the level of agreement (Gwet's AC1)
      between Observers A and B and sensitivity/specificity values for the respective
      Observers were, by site: vagina (Gwet's AC1, 0.933; 62%/94% and 82%/94%), bladder
      (Gwet's AC1, 1.00; 67%/97% and 67%/97%), uterosacral ligaments (Gwet's AC1, 0.84;
      73%/83% and 53%/90%), adnexa (Gwet's AC1, 0.95; 71%/93% and 71%/93%),
      rectovaginal septum (Gwet's AC1, 0.95; 40%/90% and 33%/87%) and rectosigmoid
      (Gwet's AC1, 0.98; 93%/96% and 94%/98%) which reflected high interobserver
      agreement. With the exception of sensitivity of diagnosis of DIE affecting the
      RVS, similar results were observed when TVS was compared with laparoscopy.
      CONCLUSIONS: TVS is a highly accurate and reproducible method for non-invasive
      diagnosis of DIE by well-trained professionals.

PMID- 25766662
TI  - Ethical Guidelines for Organ Transplantation from Deceased Donors.

PMID- 25766659
TI  - Molecular mechanisms of ethanol-associated oro-esophageal squamous cell
      carcinoma.
AB  - Alcohol drinking is a major etiological factor of oro-esophageal squamous cell
      carcinoma (OESCC). Both local and systemic effects of ethanol may promote
      carcinogenesis, especially among chronic alcoholics. However, molecular
      mechanisms of ethanol-associated OESCC are still not well understood. In this
      review, we summarize current understandings and propose three mechanisms of
      ethanol-associated OESCC: (1) Disturbance of systemic metabolism of nutrients:
      during ethanol metabolism in the liver, systemic metabolism of retinoids, zinc,
      iron and methyl groups is altered. These nutrients are known to be associated
      with the development of OESCC. (2) Disturbance of redox metabolism in squamous
      epithelial cells: when ethanol is metabolized in oro-esophageal squamous
      epithelial cells, reactive oxygen species are generated and produce oxidative
      damage. Meanwhile, ethanol may also disturb fatty-acid metabolism in these cells.
      (3) Disturbance of signaling pathways in squamous epithelial cells: due to its
      physico-chemical properties, ethanol changes cell membrane fluidity and shape,
      and may thus impact multiple signaling pathways. Advanced molecular techniques in
      genomics, epigenomics, metabolomics and microbiomics will help us elucidate how
      ethanol promotes OESCC. 

PMID- 25766663
TI  - Early Efficacy Analysis of Biatrial Ablation versus Left and Simplified Right
      Atrial Ablation for Atrial Fibrillation Treatment in Patients with Rheumatic
      Heart Disease.
AB  - BACKGROUND: Atrial fibrillation (AF) is the most common sustained arrhythmia.
      About 60% of patients with rheumatic heart disease have persistent AF. METHODS: A
      total of 197 patients underwent valve replacement concomitant bipolar
      radiofrequency ablation (BRFA). Patients were divided into the biatrial ablation
      group and the simplified right atrial ablation group. In biatrial ablation group,
      the patients underwent a complete left and right atrial ablation. In simplified
      right atrial ablation group, the patients underwent a complete left atrial
      ablation and a simplified right atrial ablation. RESULTS: The conversion of sinus
      rhythm (SR) was high in both groups during the follow-up period. In the
      simplified right atrial ablation group, SR conversion rate was 88.29% at
      discharge. At six months and 12 months after surgery, 87.39% of patients and
      86.49% of patients were in SR free of antiarrhythmic drugs, respectively. While
      in the biatrial ablation group, SA conversion rate was 89.53% at discharge.
      Percentage of patients in SR free of antiarrhythmic drugs was 88.37% and 88.37%
      at six months and 12 months after surgery, respectively. Echocardiography showed
      left atrial diameter decreased significantly after the surgery in the two groups.
      The ejection fraction and fractional shortening were improved significantly,
      without significant differences between the two groups. CONCLUSIONS: The results
      suggest that the concomitant left atrial and simplified right atrial BRFA for AF
      in patients undergoing valve replacement can achieve similar early efficiency as
      biatrial ablation.

PMID- 25766664
TI  - The Role of Colchicine in Pericarditis--A Systematic Review and Meta-analysis of
      Randomised Trials.
AB  - INTRODUCTION: Colchicine has been used in diverse clinical settings. Primary
      idiopathic pericarditis is complicated by recurrence in 15 to 30% of cases.
      Aspirin, non-steroidal anti-inflammatory drugs, colchicine and steroids are the
      commonly prescribed medications. We synthesised the available evidence from the
      randomised trials to assess the efficacy and safety of colchicine in primary and
      recurrent pericarditis. METHODS: A systematic search was conducted using MEDLINE,
      PubMed, EMBASE, Current Contents Connect, Cochrane library, Google Scholar,
      Science Direct, and Web of Science. Original data was abstracted from each study
      and used to calculate an odds ratio (OR) and 95% confidence interval (95% CI).
      RESULTS: Seven randomised trials comprising 1275 patients met full criteria for
      analysis. Two open label randomised controlled trials and five double-blind
      randomised controlled trials were included. Colchicine was useful in reducing the
      incidence of primary pericarditis (OR: 0.38, 95% CI: 0.22- 0.65) as well as
      recurrent pericarditis (OR: 0.31, 95% CI: 0.22-0.44). The most common side
      effects were related to the gastrointestinal system and no severe adverse events
      were observed. Colchicine cessation either by patient or physician was similar in
      both groups (OR: 1.53, 95% CI: 0.86-2.71). CONCLUSION: Colchicine is effective in
      preventing both primary and recurrent episodes of pericarditis. The number needed
      to treat for preventing recurrent pericarditis was five. Gastrointestinal side
      effects were the most common adverse events.

PMID- 25766666
TI  - Small exotic companion mammal wellness management and environmental enrichment.
AB  - Wellness management and environmental enrichment are important components of
      preventative veterinary medical care. Small exotic mammals represent a diverse
      group of pets with widely varying types of care, diet, and husbandry
      considerations; thus, environmental enrichment must go beyond the cage or tank
      design in order to provide proper mental fitness in meeting any pet's
      psychological needs. Addressing the pet's environmental, dietary, exercise, and
      social needs is vital to keeping these animals healthier and more disease
      resistant. The key to accomplishing this is largely impacted by the annual or
      biannual veterinary wellness visit and a commitment from the pet's owner. 

PMID- 25766665
TI  - Role of capsular modified heptose in the virulence of Campylobacter jejuni.
AB  - The Campylobacter jejuni capsular polysaccharide is important for virulence and
      often contains a modified heptose. In strain ATCC 700819 (a.k.a. NCTC 11168), the
      modified heptose branches off from the capsular backbone and is directly exposed
      to the environment. We reported previously that the enzymes encoded by wcaG,
      mlghB and mlghC are involved in heptose modification. Here, we show that
      inactivation of any of these genes leads to production of capsule lacking
      modified heptose and alters the transcription of other capsule modification genes
      differentially. Inactivation of mlghB or mlghC, but not of wcaG, decreased
      susceptibility to bile salts and abrogated invasion of intestinal cells. All
      mutants showed increased sensitivity to serum killing, especially wcaG::cat, and
      had defects in colonization and persistence in chicken intestine, but did not
      show significant differences in adhesion, phagocytosis and intracellular survival
      in murine macrophages. Together, our findings suggest that the capsular heptose
      modification pathway contributes to bacterial resistance against gastrointestinal
      host defenses and supports bacterial persistence via its role in serum resistance
      and invasion of intestinal cells. Our data further suggest a dynamic regulation
      of expression of this pathway in the gastrointestinal tract. 

PMID- 25766667
TI  - Reptile wellness management.
AB  - Proper care and husbandry are the most important factors in keeping captive
      reptiles healthy. Improper nutrition, supplementation, caging, lighting,
      substrate, temperature, and humidity can all lead to stress and development of
      disease. Presented here are current recommendations for keeping captive reptiles.
      Care has moved away from sterile, spartan enclosures to larger, more naturalistic
      habitats. These habitats provide more space and choices for the reptile, leading
      to higher activity levels, reduced stress, and more opportunities to exhibit
      natural behaviors. Reptiles benefit from enrichment and are amenable to training
      in order to reduce stress and allow easier handling and veterinary care. 

PMID- 25766669
TI  - Outcomes following implementation of symptom triggered diagnostic testing for
      ovarian cancer.
AB  - OBJECTIVES: UK is the first country to implement symptom triggered testing for
      suspected ovarian cancer (OC) following guidance from National Institute of
      Clinical Excellence in 2011. We evaluated its impact on cancer outcomes and
      implications on clinical practice. STUDY DESIGN: This is a cohort study and we
      analysed data for all new urgent referrals for suspected OC from two large
      teaching hospitals using a prospectively collected electronic referral database,
      supplemented with clinical data from electronic records. We evaluated outcomes
      prior to (2011) and after (2013) implementation of guidance to evaluate stage
      shift, referrals workload and surgical procedures generated. RESULTS: Secondary
      care received 2185 new referrals from primary care for women with suspected
      gynaecological cancer in post guideline cohort. Of these, 217 women were referred
      for suspected OC. 90% of primary care referrals were not compliant with guidance.
      Following implementation of guidance, more women with OC were diagnosed through
      urgent referral (rapid access clinics): Almost double, 21 of the total 67
      (31.34%) OCs in 2013 (post guidance) in comparison to only 11 of 69 OCs (15.94%)
      were diagnosed in 2011 (pre guidance) through urgent referrals, p=0.03. The
      predictive value of detecting cancer through rapid access clinics increased, from
      4.5% to 9.6%, p=0.04; however, no stage shift was noted. Over 25% of patients
      underwent surgeries for non-malignant conditions in the post-guideline cohort. No
      increase was seen in workload of cancer clinics. CONCLUSION: Implementation of
      Symptom-triggered testing is challenging in clinical practice. Such testing
      results in more patients with OC accessing expedited care pathways leading to
      streamlined routes of diagnosis and care. However, current implementation does
      not lead to stage shift in diagnosis and may not achieve significant mortality
      benefit.

PMID- 25766670
TI  - Is weight loss an outcome of or a contributory factor for vascular dementia in
      frail elderly people?

PMID- 25766668
TI  - The germline of the malaria mosquito produces abundant miRNAs, endo-siRNAs,
      piRNAs and 29-nt small RNAs.
AB  - BACKGROUND: Small RNAs include different classes essential for endogenous gene
      regulation and cellular defence against genomic parasites. However, a
      comprehensive analysis of the small RNA pathways in the germline of the mosquito
      Anopheles gambiae has never been performed despite their potential relevance to
      reproductive capacity in this malaria vector. RESULTS: We performed small RNA
      deep sequencing during larval and adult gonadogenesis and find that they
      predominantly express four classes of regulatory small RNAs. We identified 45
      novel miRNA precursors some of which were sex-biased and gonad-enriched , nearly
      doubling the number of previously known miRNA loci. We also determine multiple
      genomic clusters of 24-30 nt Piwi-interacting RNAs (piRNAs) that map to
      transposable elements (TEs) and 3'UTR of protein coding genes. Unusually, many
      TEs and the 3'UTR of some endogenous genes produce an abundant peak of 29-nt
      small RNAs with piRNA-like characteristics. Moreover, both sense and antisense
      piRNAs from TEs in both Anopheles gambiae and Drosophila melanogaster reveal
      novel features of piRNA sequence bias. We also discovered endogenous small
      interfering RNAs (endo-siRNAs) that map to overlapping transcripts and TEs.
      CONCLUSIONS: This is the first description of the germline miRNome in a mosquito
      species and should prove a valuable resource for understanding gene regulation
      that underlies gametogenesis and reproductive capacity. We also provide the first
      evidence of a piRNA pathway that is active against transposons in the germline
      and our findings suggest novel piRNA sequence bias. The contribution of small RNA
      pathways to germline TE regulation and genome defence in general is an important
      finding for approaches aimed at manipulating mosquito populations through the use
      of selfish genetic elements.

PMID- 25766671
TI  - Reaction-diffusion degradation model for delayed erosion of cross-linked
      polyanhydride biomaterials.
AB  - We develop a theoretical model to explain the long induction interval of water
      intake that precedes the onset of erosion due to degradation caused by hydrolysis
      in the recently synthesized and studied cross-linked polyanhydrides. Various
      kinetic mechanisms are incorporated in the model in an attempt to explain the
      experimental data for the mass loss profile. Our key finding is that the observed
      long induction interval is attributable to the nonlinear dependence of the
      degradation rate constants on the local water concentration, which essentially
      amounts to the breakdown of the standard rate-equation approach, potential causes
      for which are then discussed. Our theoretical results offer physical insights
      into which microscopic studies will be required to supplement the presently
      available macroscopic mass-loss data in order to fully understand the origin of
      the observed behavior. 

PMID- 25766672
TI  - Silicene nanomesh.
AB  - Similar to graphene, zero band gap limits the application of silicene in
      nanoelectronics despite of its high carrier mobility. By using first-principles
      calculations, we reveal that a band gap is opened in silicene nanomesh (SNM) when
      the width W of the wall between the neighboring holes is even. The size of the
      band gap increases with the reduced W and has a simple relation with the ratio of
      the removed Si atom and the total Si atom numbers of silicene. Quantum transport
      simulation reveals that the sub-10 nm single-gated SNM field effect transistors
      show excellent performance at zero temperature but such a performance is greatly
      degraded at room temperature.

PMID- 25766673
TI  - Manipulations of amyloid precursor protein cleavage disrupt the circadian clock
      in aging Drosophila.
AB  - Alzheimer's disease (AD) is a neurodegenerative disease characterized by severe
      cognitive deterioration. While causes of AD pathology are debated, a large body
      of evidence suggests that increased cleavage of Amyloid Precursor Protein (APP)
      producing the neurotoxic Amyloid-beta (Abeta) peptide plays a fundamental role in
      AD pathogenesis. One of the detrimental behavioral symptoms commonly associated
      with AD is the fragmentation of sleep-activity cycles with increased nighttime
      activity and daytime naps in humans. Sleep-activity cycles, as well as
      physiological and cellular rhythms, which may be important for neuronal
      homeostasis, are generated by a molecular system known as the circadian clock.
      Links between AD and the circadian system are increasingly evident but not well
      understood. Here we examined whether genetic manipulations of APP-like (APPL)
      protein cleavage in Drosophila melanogaster affect rest-activity rhythms and core
      circadian clock function in this model organism. We show that the increased beta
      cleavage of endogenous APPL by the beta-secretase (dBACE) severely disrupts
      circadian behavior and leads to reduced expression of clock protein PER in
      central clock neurons of aging flies. Our data suggest that behavioral rhythm
      disruption is not a product of APPL-derived Abeta production but rather may be
      caused by a mechanism common to both alpha and beta-cleavage pathways.
      Specifically, we show that increased production of the endogenous Drosophila
      Amyloid Intracellular Domain (dAICD) caused disruption of circadian rest-activity
      rhythms, while flies overexpressing endogenous APPL maintained stronger circadian
      rhythms during aging. In summary, our study offers a novel entry point toward
      understanding the mechanism of circadian rhythm disruption in Alzheimer's
      disease. 

PMID- 25766674
TI  - Zn II(atsm) is protective in amyotrophic lateral sclerosis model mice via a
      copper delivery mechanism.
AB  - Mutations in the metalloprotein Cu,Zn-superoxide dismutase (SOD1) cause
      approximately 20% of familial cases of amyotrophic lateral sclerosis (ALS), a
      fatal neurodegenerative disease for which effective therapeutics do not yet
      exist. Transgenic rodent models based on over-expression of mutant SOD1 have been
      developed and these have provided opportunity to test new therapeutic strategies
      and to study the mechanisms of mutant SOD1 toxicity. Although the mechanisms of
      mutant SOD1 toxicity are yet to be fully elucidated, incorrect or incomplete
      metallation of SOD1 confers abnormal folding, aggregation and biochemical
      properties, and improving the metallation state of SOD1 provides a viable
      therapeutic option. The therapeutic effects of delivering copper (Cu) to mutant
      SOD1 have been demonstrated recently. The aim of the current study was to
      determine if delivery of zinc (Zn) to SOD1 was also therapeutic. To investigate
      this, SOD1G37R mice were treated with the metal complex diacetyl-bis(4
      methylthiosemicarbazonato)zinc(II) [Zn(II)(atsm)]. Treatment resulted in an
      improvement in locomotor function and survival of the mice. However, biochemical
      analysis of spinal cord tissue collected from the mice revealed that the
      treatment did not increase overall Zn levels in the spinal cord nor the Zn
      content of SOD1. In contrast, overall levels of Cu in the spinal cord were
      elevated in the Zn(II)(atsm)-treated SOD1G37R mice and the Cu content of SOD1 was
      also elevated. Further experiments demonstrated transmetallation of Zn(II)(atsm)
      in the presence of Cu to form the Cu-analogue Cu(II)(atsm), indicating that the
      observed therapeutic effects for Zn(II)(atsm) in SOD1G37R mice may in fact be due
      to in vivo transmetallation and subsequent delivery of Cu.

PMID- 25766675
TI  - SOX11 identified by target gene evaluation of miRNAs differentially expressed in
      focal and non-focal brain tissue of therapy-resistant epilepsy patients.
AB  - MicroRNAs (miRNAs) are small non-coding RNAs that post-transcriptionally control
      the expression of their target genes via RNA interference. There is increasing
      evidence that expression of miRNAs is dysregulated in neuronal disorders,
      including epilepsy, a chronic neurological disorder characterized by spontaneous
      recurrent seizures. Mesial temporal lobe epilepsy (MTLE) is a common type of
      focal epilepsy in which disease-induced abnormalities of hippocampal neurogenesis
      in the subgranular zone as well as gliosis and neuronal cell loss in the cornu
      ammonis area are reported. We hypothesized that in MTLE altered miRNA-mediated
      regulation of target genes could be involved in hippocampal cell remodeling. A
      miRNA screen was performed in hippocampal focal and non-focal brain tissue
      samples obtained from the temporal neocortex (both n=8) of MTLE patients. Out of
      215 detected miRNAs, two were differentially expressed (hsa-miR-34c-5p: mean
      increase of 5.7 fold (p=0.014), hsa-miR-212-3p: mean decrease of 76.9%
      (p=0.0014)). After in-silico target gene analysis and filtering, reporter gene
      assays confirmed RNA interference for hsa-miR-34c-5p with 3'-UTR sequences of
      GABRA3, GRM7 and GABBR2 and for hsa-miR-212-3p with 3'-UTR sequences of SOX11,
      MECP2, ADCY1 and ABCG2. Reporter gene assays with mutated 3'-UTR sequences of the
      transcription factor SOX11 identified two different binding sites for hsa-miR-212
      3p and its primary transcript partner hsa-miR-132-3p. Additionally, there was an
      inverse time-dependent expression of Sox11 and miR-212-3p as well as miR-132-3p
      in rat neonatal cortical neurons. Transfection of neurons with anti-miRs for miR
      212-3p and miR-132-3p suggest that both miRNAs work synergistically to control
      Sox11 expression. Taken together, these results suggest that differential miRNA
      expression in neurons could contribute to an altered function of the
      transcription factor SOX11 and other genes in the setting of epilepsy, resulting
      not only in impaired neural differentiation, but also in imbalanced neuronal
      excitability and accelerated drug export. 

PMID- 25766677
TI  - D1 dopamine receptor stimulation impairs striatal proteasome activity in
      Parkinsonism through 26S proteasome disassembly.
AB  - Among the mechanisms underlying the development of L-dopa-induced dyskinesia
      (LID) in Parkinson's disease, complex alterations in dopamine signaling in D1
      receptor (D1R)-expressing medium spiny striatal neurons have been unraveled such
      as, but not limited to, dysregulation of D1R expression, lateral diffusion,
      intraneuronal trafficking, subcellular localization and desensitization, leading
      to a pathological anchorage of D1R at the plasma membrane. Such anchorage is
      partly due to a decreased proteasomal activity that is specific of the L-dopa
      exposed dopamine-depleted striatum, results from D1R activation and feeds-back
      the D1R exaggerated cell surface abundance. The precise mechanisms by which L
      dopa affects striatal proteasome activity remained however unknown. We here show,
      in a series of in vitro ex vivo and in vivo models, that such rapid modulation of
      striatal proteasome activity intervenes through D1R-mediated disassembly of the
      26S proteasome rather than change in transcription or translation of proteasome
      or proteasome subunits intraneuronal relocalization. 

PMID- 25766676
TI  - Alterations in sociability and functional brain connectivity caused by early-life
      seizures are prevented by bumetanide.
AB  - There is a well-described association between infantile epilepsy and pervasive
      cognitive and behavioral deficits, including a high incidence of autism spectrum
      disorders. Despite the robustness of the relationship between early-life seizures
      and the development of autism, the pathophysiological mechanism by which this
      occurs has not been explored. As a result of increasing evidence that autism is a
      disorder of brain connectivity we hypothesized that early-life seizures would
      interrupt normal brain connectivity during brain maturation and result in an
      autistic phenotype. Normal rat pups underwent recurrent flurothyl-induced
      seizures from postnatal (P)days 5-14 and then tested, along with controls, for
      developmental alterations of development brain oscillatory activity from P18-P25.
      Specifically we wished to understand how normal changes in rhythmicity in and
      between brain regions change as a function of age and if this rhythmicity is
      altered or interrupted by early life seizures. In rat pups with early-life
      seizures, field recordings from dorsal and ventral hippocampus and prefrontal
      cortex demonstrated marked increase in coherence as well as a decrease in voltage
      correlation at all bandwidths compared to controls while there were minimal
      differences in total power and relative power spectral densities. Rats with early
      life seizures had resulting impairment in the sociability and social novelty
      tests but demonstrated no evidence of increased activity or generalized anxiety
      as measured in the open field. In addition, rats with early-life seizures had
      lower seizure thresholds than controls, indicating long-standing alterations in
      the excitatory/inhibition balance. Bumetanide, a pharmacological agent that
      blocks the activity of NKCC1 and induces a significant shift of ECl toward more
      hyperpolarized values, administration at the time of the seizures precluded the
      subsequent abnormalities in coherence and voltage correlation and resulted in
      normal sociability and seizure threshold. Taken together these findings indicate
      that early-life seizures alter the development of oscillations and result in
      autistic-like behaviors. The altered communication between these brain regions
      could reflect the physiological underpinnings underlying social cognitive
      deficits seen in autism spectrum disorders. 

PMID- 25766678
TI  - Sleep impairment and reduced interneuron excitability in a mouse model of Dravet
      Syndrome.
AB  - Dravet Syndrome (DS) is caused by heterozygous loss-of-function mutations in
      voltage-gated sodium channel NaV1.1. Our mouse genetic model of DS recapitulates
      its severe seizures and premature death. Sleep disturbance is common in DS, but
      its mechanism is unknown. Electroencephalographic studies revealed abnormal sleep
      in DS mice, including reduced delta wave power, reduced sleep spindles, increased
      brief wakes, and numerous interictal spikes in Non-Rapid-Eye-Movement sleep.
      Theta power was reduced in Rapid-Eye-Movement sleep. Mice with NaV1.1 deleted
      specifically in forebrain interneurons exhibited similar sleep pathology to DS
      mice, but without changes in circadian rhythm. Sleep architecture depends on
      oscillatory activity in the thalamocortical network generated by excitatory
      neurons in the ventrobasal nucleus (VBN) of the thalamus and inhibitory GABAergic
      neurons in the reticular nucleus of the thalamus (RNT). Whole-cell NaV current
      was reduced in GABAergic RNT neurons but not in VBN neurons. Rebound firing of
      action potentials following hyperpolarization, the signature firing pattern of
      RNT neurons during sleep, was also reduced. These results demonstrate imbalance
      of excitatory vs. inhibitory neurons in this circuit. As predicted from this
      functional impairment, we found substantial deficit in homeostatic rebound of
      slow wave activity following sleep deprivation. Although sleep disorders in
      epilepsies have been attributed to anti-epileptic drugs, our results show that
      sleep disorder in DS mice arises from loss of NaV1.1 channels in forebrain
      GABAergic interneurons without drug treatment. Impairment of NaV currents and
      excitability of GABAergic RNT neurons are correlated with impaired sleep quality
      and homeostasis in these mice. 

PMID- 25766680
TI  - Whole genome comparative analysis of transposable elements provides new insight
      into mechanisms of their inactivation in fungal genomes.
AB  - BACKGROUND: Transposable Elements (TEs) are key components that shape the
      organization and evolution of genomes. Fungi have developed defense mechanisms
      against TE invasion such as RIP (Repeat-Induced Point mutation), MIP (Methylation
      Induced Premeiotically) and Quelling (RNA interference). RIP inactivates repeated
      sequences by promoting Cytosine to Thymine mutations, whereas MIP only methylates
      TEs at C residues. Both mechanisms require specific cytosine DNA
      Methyltransferases (RID1/Masc1) of the Dnmt1 superfamily. RESULTS: We annotated
      TE sequences from 10 fungal genomes with different TE content (1-70%). We then
      used these TE sequences to carry out a genome-wide analysis of C to T mutations
      biases. Genomes from either Ascomycota or Basidiomycota that were massively
      invaded by TEs (Blumeria, Melampsora, Puccinia) were characterized by a low
      frequency of C to T mutation bias (10-20%), whereas other genomes displayed
      intermediate to high frequencies (25-75%). We identified several dinucleotide
      signatures at these C to T mutation sites (CpA, CpT, and CpG). Phylogenomic
      analysis of fungal Dnmt1 MTases revealed a previously unreported association
      between these dinucleotide signatures and the presence/absence of sub-classes of
      Dnmt1. CONCLUSIONS: We identified fungal genomes containing large numbers of TEs
      with many C to T mutations associated with species-specific dinucleotide
      signatures. This bias suggests that a basic defense mechanism against TE invasion
      similar to RIP is widespread in fungi, although the efficiency and specificity of
      this mechanism differs between species. Our analysis revealed that dinucleotide
      signatures are associated with the presence/absence of specific Dnmt1
      subfamilies. In particular, an RID1-dependent RIP mechanism was found only in
      Ascomycota.

PMID- 25766681
TI  - Development and evaluation of short forms of the Pain Catastrophizing Scale and
      the Pain Self-efficacy Questionnaire.
AB  - BACKGROUND: To facilitate efficient screening and reduce the length of
      comprehensive self-report batteries, a four-item short form of the Pain
      Catastrophizing Scale (PCS) and a two-item short form of the Pain Self-Efficacy
      Questionnaire (PSEQ) have been developed and evaluated in samples of patients
      with arm and upper extremity pain. AIMS: The first aim of this study was to
      evaluate these short forms in a heterogeneous sample of patients seeking
      treatment for chronic musculoskeletal pain, using a priori criteria for
      determining adequate internal consistency, construct validity and sensitivity to
      change. In addition, the findings of past studies were used to identify items
      suitable for new and potentially stronger short forms of these measures. METHOD:
      Data were provided by 280 patients who completed the original PCS and PSEQ as
      part of an interdisciplinary rehabilitation programme. RESULTS: The previously
      developed four-item PCS and the newly developed six-item short form of the PCS
      both met the internal consistency and construct validity criteria. They did not
      meet the criterion regarding sensitivity to change. However, similar to what was
      obtained using the original PCS, large effect sizes were found when using these
      short forms to examine pre-treatment to post-treatment changes in
      catastrophizing. For the PSEQ, the new four-item short form was clearly superior
      to the other alternatives and met all three criteria. CONCLUSION: The strongest
      short forms of the PCS and PSEQ could facilitate the assessment of pain
      catastrophizing and self-efficacy in situations in which the use of the longer
      original measures is not feasible.

PMID- 25766682
TI  - Association between the interleukin-6 gene polymorphisms and renal cancer risk.
AB  - INTRODUCTION: Interleukin-6 (IL-6), a central proinflammatory cytokine, may be
      involved in the host response to cancer. We therefore aimed to evaluate the
      association of the IL-6 gene polymorphisms at positions -174 and -572 with
      predisposition to renal cancer. MATERIALS AND METHODS: We conducted a hospital
      based case-control study. A total of 432 subjects, including 216 pathologically
      proven renal cancer cases and 216 age- and gender-matched healthy controls, were
      recruited in this study. Polymorphism for the IL-6 gene was genotyped by
      polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP).
      RESULTS: Patients with renal cancer had a significantly higher frequency of IL-6 
      174 CC genotype [odds ratio (OR)=2.08, 95% confidence interval (CI)=1.05, 4.13;
      P=0.04] than healthy controls. When stratifying by the grade, patients with
      higher grade (grade 3 or 4) renal cancer had a significantly higher frequency of
      IL-6 -174 CC genotype (OR=2.33, 95% CI=1.04, 5.23; P=0.04). CONCLUSION: This
      study is, to our knowledge, the first to examine prospectively an increased risk
      role of IL-6 -174 CC genotype in renal cancer susceptibility.

PMID- 25766679
TI  - Glia and alpha-synuclein in neurodegeneration: A complex interaction.
AB  - alpha-Synucleinopathies (ASP) comprise adult-onset, progressive neurodegenerative
      disorders such as Parkinson's disease (PD), dementia with Lewy bodies (DLB) and
      multiple system atrophy (MSA) that are characterized by alpha-synuclein (AS)
      aggregates in neurons or glia. PD and DLB feature neuronal AS-positive inclusions
      termed Lewy bodies (LB) whereas glial cytoplasmic inclusions (GCIs, Papp-Lantos
      bodies) are recognized as the defining hallmark of MSA. Furthermore, AS-positive
      cytoplasmic aggregates may also be seen in astroglial cells of PD/DLB and MSA
      brains. The glial AS-inclusions appear to trigger reduced trophic support
      resulting in neuronal loss. Moreover, microgliosis and astrogliosis can be found
      throughout the neurodegenerative brain and both are key players in the initiation
      and progression of ASP. In this review, we will highlight AS-dependent
      alterations of glial function and their impact on neuronal vulnerability thereby
      providing a detailed summary on the multifaceted role of glia in ASP. 

PMID- 25766684
TI  - Metagenomics: a new frontier for translational research and personalized
      therapeutics in psychiatry?

PMID- 25766683
TI  - Enrichment of inflammatory bowel disease and colorectal cancer risk variants in
      colon expression quantitative trait loci.
AB  - BACKGROUND: Genome-wide association studies (GWAS) have identified single
      nucleotide polymorphisms (SNPs) associated with diseases of the colon including
      inflammatory bowel diseases (IBD) and colorectal cancer (CRC). However, the
      functional role of many of these SNPs is largely unknown and tissue-specific
      resources are lacking. Expression quantitative trait loci (eQTL) mapping
      identifies target genes of disease-associated SNPs. This study provides a
      comprehensive eQTL map of distal colonic samples obtained from 40 healthy African
      Americans and demonstrates their relevance for GWAS of colonic diseases. RESULTS:
      8.4 million imputed SNPs were tested for their associations with 16,252
      expression probes representing 12,363 unique genes. 1,941 significant cis-eQTL,
      corresponding to 122 independent signals, were identified at a false discovery
      rate (FDR) of 0.01. Overall, among colon cis-eQTL, there was significant
      enrichment for GWAS variants for IBD (Crohn's disease [CD] and ulcerative colitis
      [UC]) and CRC as well as type 2 diabetes and body mass index. ERAP2, ADCY3,
      INPP5E, UBA7, SFMBT1, NXPE1 and REXO2 were identified as target genes for IBD
      associated variants. The CRC-associated eQTL rs3802842 was associated with the
      expression of C11orf93 (COLCA2). Enrichment of colon eQTL near transcription
      start sites and for active histone marks was demonstrated, and eQTL with high
      population differentiation were identified. CONCLUSIONS: Through the
      comprehensive study of eQTL in the human colon, this study identified novel
      target genes for IBD- and CRC-associated genetic variants. Moreover,
      bioinformatic characterization of colon eQTL provides a tissue-specific tool to
      improve understanding of biological differences in diseases between different
      ethnic groups.

PMID- 25766685
TI  - What causes eating disorders, and what do they cause?

PMID- 25766686
TI  - Valuation and cognitive circuitry in anorexia nervosa: disentangling appetite
      from the effort to obtain a reward.

PMID- 25766688
TI  - Correction.

PMID- 25766687
TI  - Electronic cigarettes: pro.

PMID- 25766690
TI  - Year in review 2014. Paediatric and adult clinical studies.

PMID- 25766689
TI  - Role of primary care in the follow-up of patients with obstructive sleep apnoea
      undergoing CPAP treatment: a randomised controlled trial.
AB  - OBJECTIVE: To evaluate whether follow-up of patients with obstructive sleep
      apnoea (OSA) undergoing CPAP treatment could be performed in primary care (PC)
      settings. DESIGN: Non-inferiority, randomised, prospective controlled study.
      SETTINGS: Sleep unit (SU) at the University Hospital and in 8 PC units in Lleida,
      Spain. PARTICIPANTS: Patients with OSA were randomised to be followed up at the
      SU or PC units over a 6-month period. MAIN OUTCOMES MEASURED: The primary outcome
      was CPAP compliance at 6 months. The secondary outcomes were Epworth Sleep Scale
      (ESS) score, EuroQoL, patient satisfaction, body mass index (BMI), blood pressure
      and cost-effectiveness. RESULTS: We included 101 patients in PC ((mean+/-SD)
      apnoea-hypopnoea index (AHI) 50.8+/-22.9/h, age 56.2+/-11 years, 74% male) and
      109 in the SU (AHI 51.4+/-24.4/h, age 55.8+/-11 years, 77% male)). The CPAP
      compliance was (mean (95% CI) 4.94 (4.47 to 5.5) vs 5.23 (4.79 to 5.66) h,
      p=0.18) in PC and SU groups, respectively. In the SU group, there were greater
      improvements in ESS scores (mean change 1.79, 95% CI +0.05 to +3.53, p=0.04) and
      patient satisfaction (-1.49, 95% CI -2.22 to -0.76); there was a significant mean
      difference in BMI between the groups (0.57, 95% CI +0.01 to +1.13, p=0.04). In
      the PC setting, there was a cost saving of 60%, with similar effectiveness, as
      well as a decrease in systolic blood pressure (-5.32; 95% CI -10.91 to +0.28,
      p=0.06). CONCLUSIONS: For patients with OSA, treatment provided in a PC setting
      did not result in worse CPAP compliance compared with a specialist model and was
      shown to be a cost-effective alternative. TRIAL REGISTRATION NUMBER: Clinical
      Trials NCT01918449.

PMID- 25766691
TI  - Max Klein: a great man and a great paediatrician.

PMID- 25766693
TI  - A 1D pulse wave propagation model of the hemodynamics of calf muscle pump
      function.
AB  - The calf muscle pump is a mechanism which increases venous return and thereby
      compensates for the fluid shift towards the lower body during standing. During a
      muscle contraction, the embedded deep veins collapse and venous return increases.
      In the subsequent relaxation phase, muscle perfusion increases due to increased
      perfusion pressure, as the proximal venous valves temporarily reduce the distal
      venous pressure (shielding). The superficial and deep veins are connected via
      perforators, which contain valves allowing flow in the superficial-to-deep
      direction. The aim of this study is to investigate and quantify the physiological
      mechanisms of the calf muscle pump, including the effect of venous valves,
      hydrostatic pressure, and the superficial venous system. Using a one-dimensional
      pulse wave propagation model, a muscle contraction is simulated by increasing the
      extravascular pressure in the deep venous segments. The hemodynamics are studied
      in three different configurations: a single artery-vein configuration with and
      without valves and a more detailed configuration including a superficial vein.
      Proximal venous valves increase effective venous return by 53% by preventing
      reflux. Furthermore, the proximal valves shielding function increases perfusion
      following contraction. Finally, the superficial system aids in maintaining the
      perfusion during the contraction phase and reduces the refilling time by 37%.

PMID- 25766694
TI  - BRCA1 and CtIP promote alternative non-homologous end-joining at uncapped
      telomeres.

PMID- 25766695
TI  - Continuous Positive Airway Pressure Treatment Increases Serum Vitamin D Levels in
      Male Patients with Obstructive Sleep Apnea.
AB  - STUDY OBJECTIVE: Recent studies report a link between obstructive sleep apnea
      (OSA) syndrome, low vitamin D levels, and high parathyroid hormone (PTH)
      concentrations. The aim of the current study is to evaluate the effect of 7-night
      continuous positive airway pressure (CPAP) therapy on serum vitamin D, PTH, and
      calcium levels in patients with severe OSA syndrome. METHODS: Patients with
      severe OSA were enrolled into the study and compared to control subjects.
      Patients with OSA underwent CPAP therapy for 7 nights and were consequently
      divided into responders (OSA-R, mean residual AHI < 5/h) and nonresponders (OSA
      nR, mean residual AHI > 5/h). Serum vitamin D, PTH, and calcium levels were
      measured at baseline in patients with severe OSA (apnea-hypopnea index > 30/h)
      and control subjects. Patients with OSA underwent a final morning blood sample
      after 7-night CPAP therapy. RESULTS: We enrolled 90 patients with OSA into the
      study (65 OSA-R and 25 OSA-nR) compared to 32 control subjects. At baseline,
      lower vitamin D and higher PTH levels were detected in the OSA group compared to
      controls. After 7-night CPAP therapy, male OSA-R patients showed a significant
      increase in vitamin D levels. Conversely, female OSA-R patients did not show the
      same increase in vitamin D levels. It was also observed that OSA-nR subjects did
      not show modifications of serum markers after nCPAP-therapy. CONCLUSIONS: The
      study demonstrates that short-term nCPAP treatment is able to promote the
      recovery of vitamin D homeostasis in male patients with OSA. The mediation of
      sexual hormones in regulating vitamin D is a possible explanation of the lack of
      recovery of vitamin D homeostasis in female patients with OSA as it often affects
      postmenopausal women.

PMID- 25766696
TI  - Risk of psychiatric disorders in patients with chronic insomnia and sedative
      hypnotic prescription: a nationwide population-based follow-up study.
AB  - STUDY OBJECTIVES: Previous epidemiological studies have established insomnia as a
      major risk factor for mood, anxiety, and substance use disorders. However, the
      associations between insomnia with sedative-hypnotic prescriptions and various
      psychiatric disorders have not been thoroughly examined. The current study
      involved evaluating the risk of psychiatric disorders, namely schizophrenia,
      mood, anxiety, somatoform, and substance-related disorders, over a 6-y follow-up
      period in three groups: patients with insomnia and sedative-hypnotic
      prescriptions (Inso-Hyp), those with insomnia and without sedative-hypnotic
      prescriptions (Inso-NonHyp), and those with neither insomnia nor sedative
      hypnotic prescriptions (NonInso-NonHyp). METHODS: We used a historical cohort
      study design to compare the risk of psychiatric disorders among the three groups.
      Data regarding these patients were derived from reimbursement claims recorded in
      Taiwan's National Health Insurance Research Database. Cox proportional hazards
      regression was used to compare the 6-y risk of subsequent psychiatric disorders
      among the Inso-Hyp, Inso-NonHyp, and NonInso-NonHyp groups. RESULTS: Compared
      with the Inso-NonHyp and NonInso-NonHyp group patients, the Inso-Hyp group
      patients exhibited a higher risk of psychiatric disorders, particularly bipolar
      disorders (adjusted hazard ratio [AHR]: 7.60; 95% confidence interval [CI]: 5.31
      10.89 and AHR: 14.69; 95% CI: 11.11-19.43, respectively). Moreover, among the
      Inso-Hyp patient group, insomnia prescribed with benzodiazepine, a longer
      duration of sedative-hypnotic action, and higher doses of sedativehypnotics were
      significantly associated with a higher risk of depressive and anxiety disorders.
      CONCLUSION: The Inso-Hyp group exhibited a higher risk of developing psychiatric
      disorders than did the Inso-NonHyp and NonInso-NonHyp groups. The results
      regarding patients with insomnia and sedative-hypnotic prescriptions associated
      with the risk of psychiatric disorders can serve as a reference for care
      providers when managing sleep disturbances.

PMID- 25766697
TI  - Nocturnal Hypoxemia and Severe Obstructive Sleep Apnea are Associated with
      Incident Type 2 Diabetes in a Population Cohort of Men.
AB  - STUDY OBJECTIVES: Studies examining the longitudinal association of untreated
      obstructive sleep apnea (OSA) with diabetes in population samples are limited.
      This study therefore examined the relationship between previously undiagnosed OSA
      with incident type 2 diabetes in community-dwelling men aged >= 40 y. METHODS:
      The Men Androgen Inflammation Lifestyle Environment and Stress (MAILES) Study is
      a longitudinal population-based cohort in Adelaide, South Australia. Clinic
      assessments at baseline and follow-up identified diabetes (self-reported doctor
      diagnosed, fasting plasma glucose >= 7.0 mmol/L, glycated hemoglobin >= 6.5% or
      diabetes medication use) and included anthropometry. At cohort follow-up (2010
      2012), n = 837 underwent full in-home unattended polysomnography (PSG, Embletta
      X100, Broomfield, CO). RESULTS: Of 736 men free of diabetes at baseline, incident
      diabetes occurred in 66 (9.0%) over a mean follow-up time of 56 mo (standard
      deviation = 5, range: 48-74 mo). Incident diabetes was associated with current
      oxygen desaturation index (3%) >= 16 events/h (odds ratio [OR]: 1.85 [1.06
      3.21]), and severe OSA [OR: 2.6 (1.1-6.1)], in adjusted models including age,
      percentage total body fat, and weight gain (> 5 cm waist circumference). An age
      adjusted association of incident diabetes with percentage of total sleep time
      with oxygen saturation < 90% did not persist after adjustment for percentage of
      body fat. No modification of these relationships by excessive daytime sleepiness
      was observed. CONCLUSIONS: Severe undiagnosed OSA and nocturnal hypoxemia were
      independently associated with the development of diabetes. A reduction in the
      burden of undiagnosed OSA and undiagnosed diabetes is likely to occur if patients
      presenting with one disorder are assessed for the other.

PMID- 25766698
TI  - Worsening of Obstructive Sleep Apnea Associated with Catheter-Related Superior
      Vena Cava Syndrome.
AB  - ABSTRACT: There is growing evidence that fluid accumulation in the neck
      contributes to the pathogenesis of obstructive sleep apnea (OSA). We describe a
      case of catheter-related superior v ena cava (SVC) thrombosis revealed by rapid
      onset of typical symptoms of OSA. A marked improvement in OSA severity was
      observed after central venous catheter removal, anticoagulant therapy, and SVC
      angioplasty.

PMID- 25766700
TI  - Rates of OSA in Patients with Major Depressive Disorder Who Were Judged To Be Low
      Risk for OSA.

PMID- 25766699
TI  - Relationship between Oral Flow Patterns, Nasal Obstruction, and Respiratory
      Events during Sleep.
AB  - STUDY OBJECTIVES: Sleep breathing patterns are altered by nasal obstruction and
      respiratory events. This study aimed to describe the relationships between
      specific sleep oral flow (OF) patterns, nasal airway obstruction, and respiratory
      events. METHODS: Nasal flow and OF were measured simultaneously by
      polysomnography in 85 adults during sleep. OF was measured 2 cm in front of the
      lips using a pressure sensor. RESULTS: OF could be classified into three
      patterns: postrespiratory event OF (postevent OF), during-respiratory event OF
      (during-event OF), and spontaneous arousal-related OF (SpAr-related OF).
      Postevent OFs begin at the end of airflow reduction, are preceded by respiratory
      arousal, and are accompanied by postapneic hyperventilation; during-event OFs
      occur during nasal flow reduction; and SpAr-related OFs to OF begin during stable
      breathing, and are preceded by spontaneous arousal but are rarely accompanied by
      apnea/hypopnea. Multivariate regression showed that nasal obstruction was
      predictive of SpAr-related OF. The relative frequency of SpAr-related OF events
      was negatively correlated with the apnea-hypopnea index. The fraction of SpAr
      related OF duration relative to total OF duration was significantly greater in
      patients with nasal obstruction than in those without. CONCLUSION: SpAr-related
      OF was associated with nasal obstruction, but not respiratory events. This
      pattern thus functions as a "nasal obstruction bypass", mainly in normal subjects
      and patients with mild sleep disordered breathing (SDB). By contrast, the other
      two types were related to respiratory events and were typical patterns seen in
      patients with moderate and severe SDB.

PMID- 25766701
TI  - Obstructive sleep apnea and mandibular advancement splints.

PMID- 25766702
TI  - Commercial Drivers with Sleep Apnea: It's Still Hit or Miss.

PMID- 25766703
TI  - Home Sleep Testing: It's Not How You Play the Game, It's Whether You Win or Lose.

PMID- 25766704
TI  - Should the arousal scoring rule be changed?

PMID- 25766705
TI  - Acoustic Analysis of Snoring in the Diagnosis of Obstructive Sleep Apnea
      Syndrome: A Call for More Rigorous Studies.
AB  - BACKGROUND: Snoring is a common symptom of obstructive sleep apnea syndrome (OSA)
      and has recently been considered for diagnosis of OSA. OBJECTIVES: The goal of
      the current study was to systematically determine the accuracy of acoustic
      analysis of snoring in the diagnosis of OSA using a meta-analysis. METHODS:
      PubMed, Cochrane Library database, and EMBASE were searched up to July 15, 2014.
      A systematic review and meta-analysis of sensitivity, specificity, and other
      measures of accuracy of acoustic analysis of snoring in the diagnosis of OSA were
      conducted. The median of apneahypopnea index threshold was 10 events/h, range: 5
      15 or 10-15 if aforementioned suggestion is adopted. RESULTS: A total of seven
      studies with 273 patients were included in the meta-analysis. The pooled
      estimates were as follows: sensitivity, 88% (95% confidence interval [CI]: 82
      93%); specificity, 81% (95% CI: 72-88%); positive likelihood ratio (PLR), 4.44
      (95% CI: 2.39-8.27); negative likelihood ratio (NLR), 0.15 (95% CI: 0.10-0.24);
      and diagnostic odds ratio (DOR), 32.18 (95% CI: 13.96-74.81). chi(2) values of
      sensitivity, specificity, PLR, NLR, and DOR were 2.37, 10.39, 12.57, 3.79, and
      6.91 respectively (All p > 0.05). The area under the summary receiver operating
      characteristic curve was 0.93. Sensitivity analysis demonstrated that the pooled
      estimates were stable and reliable. The results of publication bias were not
      significant (p = 0.30). CONCLUSIONS: Acoustic analysis of snoring is a relatively
      accurate but not a strong method for diagnosing OSA. There is an urgent need for
      rigorous studies involving large samples and single snore event tests with an
      efficacy criterion that reflects the particular features of snoring acoustics for
      OSA diagnosis.

PMID- 25766706
TI  - Sleep Related Cognitions in Individuals with Symptoms of Insomnia and Depression.
AB  - STUDY OBJECTIVES: Depression has been identified as the most common condition
      comorbid to insomnia, with findings pointing to the possibility that these
      disorders may be causally related to each other or may share common mechanisms.
      Some have suggested that comorbid insomnia and depression may have a different
      clinical course than either condition alone, and may thus require specific
      treatment procedures. In this report we examined the clinical characteristics of
      individuals referred to an academic sleep center who report comorbid symptoms of
      insomnia and depression and those with symptoms of insomnia outside the context
      of meaningful depression, and we identified differences between these groups with
      regard to several cognitive-related variables. METHODS: Logistic regression
      analyses examined whether past week worry, dysfunctional beliefs about sleep, and
      insomnia symptom-focused rumination predicted group membership. RESULTS:
      Individuals with comorbid symptoms of insomnia and depression reported more past
      week worry, dysfunctional beliefs about sleep, and insomnia symptom-focused
      rumination, than those with symptoms of insomnia without significant depression
      symptoms. When including all three cognitive-related variables in our model,
      those with comorbid symptoms reported more severe insomnia symptom-focused
      rumination, even when controlling for insomnia and mental health severity, among
      other relevant covariates. CONCLUSION: The findings contribute to our
      understanding of the complex nature of comorbid symptoms of insomnia and
      depression and the specific symptom burden experienced by those with significant
      depression symptoms in the presence of insomnia. The findings also highlight the
      need for increased clinical attention to the sleep-focused rumination reported by
      these patients.

PMID- 25766707
TI  - Predictors for Progression of Sleep Disordered Breathing among Public Transport
      Drivers: A 3-Year Follow-Up Study.
AB  - STUDY OBJECTIVES: Sleep-disordered breathing (SDB) is associated with an
      increased risk of motor vehicle crashes. This study aimed to understand SDB
      progression and related factors among professional drivers. METHODS: A total of
      524 professional male drivers from a transportation company were included in this
      study. These drivers completed overnight in-home pulse oximetry studies both in
      2006 and in 2009. Participants with abnormal results (oxygen desaturation index
      [ODI] >= 10 events/h) comprised the SDB group. Data included questionnaire
      information on demographics, medical history, SDB symptoms, and anthropometric
      measurements. RESULTS: A total of 318 male workers were recruited for further
      analysis. Fifty of these workers belonged to the SDB group. Workers with
      untreated SDB significantly progressed to a more severe state after three years.
      Baseline body mass index (BMI), baseline ODI, and change in BMI were all
      significant positive predictors of SDB progression (beta = 0.823, 0.242, and
      1.626; p = 0.047, 0.013, and 0.004, respectively). Compared with non-SDB drivers,
      SDB subjects showed a greater proportion of newly diagnosed cardiovascular
      disease (38.0%) at follow-up. CONCLUSIONS: Untreated SDB was a gradually
      progressive disorder in professional drivers over a three-year period. Subjects
      with high BMI and moderate to severe SDB should be closely monitored to allow for
      early detection of worsening SDB. Weight control should be highlighted in the
      management of SDB. COMMENTARY: A commentary on this article appears in this issue
      on page 409.

PMID- 25766708
TI  - All APAPs Are Not Equivalent for the Treatment of Sleep Disordered Breathing: A
      Bench Evaluation of Eleven Commercially Available Devices.
AB  - STUDY OBJECTIVES: This study challenged on a bench-test the efficacy of auto
      titrating positive airway pressure (APAP) devices for obstructive sleep
      disordered breathing treatment and evaluated the accuracy of the device reports.
      METHODS: Our bench consisted of an active lung simulator and a Starling resistor.
      Eleven commercially available APAP devices were evaluated on their reactions to
      single-type SDB sequences (obstructive apnea and hypopnea, central apnea, and
      snoring), and to a long general breathing scenario (5.75 h) simulating various
      SDB during four sleep cycles and to a short scenario (95 min) simulating one
      sleep cycle. RESULTS: In the single-type sequence of 30-minute repetitive
      obstructive apneas, only 5 devices normalized the airflow (> 70% of baseline
      breathing amplitude). Similarly, normalized breathing was recorded with 8 devices
      only for a 20-min obstructive hypopnea sequence. Five devices increased the
      pressure in response to snoring. Only 4 devices maintained a constant minimum
      pressure when subjected to repeated central apneas with an open upper airway. In
      the long general breathing scenario, the pressure responses and the treatment
      efficacy differed among devices: only 5 devices obtained a residual obstructive
      AHI < 5/h. During the short general breathing scenario, only 2 devices reached
      the same treatment efficacy (p < 0.001), and 3 devices underestimated the AHI by
      > 10% (p < 0.001). The long scenario led to more consistent device reports.
      CONCLUSION: Large differences between APAP devices in the treatment efficacy and
      the accuracy of report were evidenced in the current study.

PMID- 25766709
TI  - Lessons Learned from Sleep Education in Schools: A Review of Dos and Don'ts.
AB  - STUDY OBJECTIVES: Sleep duration and quality are associated with negative
      neuropsychological and psychosocial outcomes in children and adolescents.
      However, community awareness of this is low and sleep education programs in
      schools are attempting to address this issue. Several studies now exist assessing
      the efficacy of these sleep education programs for improving sleep knowledge,
      sleep hygiene and sleep patterns. This paper presents these sleep education
      programs, most particularly, it presents the strengths and weaknesses of the
      current available studies in the hope that this can identify areas where future
      sleep education programs can improve. METHODS: A systematic search of all school
      based sleep education studies in adolescents was undertaken. Studies were
      scrutinized for author, teacher and participant comment regarding strengths and
      limitations of each study, which were then extracted and summarized. RESULTS: Two
      specific types of sleep education programs emerged from the review, those that
      sought to change sleep behavior and those that sought simply to disseminate
      information. Issues that dictated the strength or weakness of a particular study
      including who delivers the program, the theoretical basis, the tools utilized to
      measure sleep patterns, the content, and their capacity to engage students were
      assessed. Sleep education was considered important by teachers, students and
      parents alike. CONCLUSIONS: Future sleep education programs need to take into
      account lessons learned from previous sleep education efforts in order to
      maximize the potential for sleep education programs to improve the sleep health
      of our young people. COMMENTARY: A commentary on this article appears in this
      issue on page 595.

PMID- 25766710
TI  - Mandibular movements identify respiratory effort in pediatric obstructive sleep
      apnea.
AB  - STUDY OBJECTIVES: Obstructive sleep apnea-hypopnea (OAH) diagnosis in children is
      based on the quantification of flow and respiratory effort (RE). Pulse transit
      time (PTT) is one validated tool to recognize RE. Pattern analysis of mandibular
      movements (MM) might be an alternative method to detect RE. We compared several
      patterns of MM to concomittant changes in PTT during OAH in children with
      adenotonsillar hypertrophy. METHODS:  PARTICIPANTS: 33 consecutive children with
      snoring and symptoms/signs of OAH. MEASUREMENTS: MMs were measured during
      polysomnography with a magnetometer device (Brizzy Nomics, Liege, Belgium) placed
      on the chin and forehead. Patterns of MM were evaluated representing peak to peak
      fluctuations > 0.3 mm in mandibular excursion (MML), mandibular opening (MMO),
      and sharp MM (MMS), which closed the mouth on cortical arousal (CAr). RESULTS:
      The median (95% CI) hourly rate of at least 1 MM (MML, or MMO, or MMS) was 18.1
      (13.2-36.3) and strongly correlated with OAHI (p = 0.003) but not with central
      apnea-hypopnea index (CAHI; p = 0.292). The durations when the MM amplitude was >
      0.4 mm and PTT > 15 ms were strongly correlated (p < 0.001). The mean (SD) of MM
      peak to peak amplitude was larger during OAH than CAH (0.9 +/- 0.7 mm and 0.2 +/-
      0.3 mm; p < 0.001, respectively). MMS at the termination of OAH had larger
      amplitude compared to MMS with CAH (1.5 +/- 0.9 mm and 0.5 +/- 0.7 mm,
      respectively, p < 0.001). CONCLUSIONS: MM > 0.4 mm occurred frequently during
      periods of OAH and were frequently terminated by MMS corresponding to mouth
      closure on CAr. The MM findings strongly correlated with changes in PTT. MM
      analysis could be a simple and accurate promising tool for RE characterization
      and optimization of OAH diagnosis in children.

PMID- 25766711
TI  - The Role of Trauma Type in the Risk for Insomnia.
AB  - OBJECTIVE: Insomnia is common following exposure to trauma and can occur
      independently or as a feature of posttraumatic stress disorder (PTSD). However,
      there is limited research identifying risk factors associated with the
      development of insomnia following exposure to a traumatic event. The goal of this
      study was to evaluate the role of specific trauma types in the risk for insomnia
      in a community sample of urban African Americans young adults. METHODS: A sample
      of 554 nonclinical, urban, young adult African Americans was recruited for a
      larger study from which 465 participants were utilized for this study based on
      their completion of all study self-report measures. Participants were initially
      screened by phone to determine whether they provisionally met study criteria.
      Once selected, participants underwent informed consent and then completed a
      battery of self-report measures that included the Life Events Checklist, the PTSD
      Checklist, the Insomnia Severity Index, and the Fear of Sleep Index. RESULTS: Of
      the seven trauma categories that were endorsed by at least 20% of the sample,
      results from logistic regression models indicated that sexual trauma, physical
      assault, accidents, natural disasters, and sudden violent death predicted
      insomnia independent of sex. However, PTSD symptom severity and nocturnal fears
      differentially influenced the relationship between trauma type and risk for
      insomnia. CONCLUSIONS: Exposure to specific types of trauma increases the odds of
      insomnia twofold to threefold. Additionally, PTSD symptom severity and nocturnal
      fears contribute differentially to the relationship between trauma exposure and
      insomnia suggesting the possibility of multiple underlying pathways.

PMID- 25766712
TI  - Minimal Effect of Daytime Napping Behavior on Nocturnal Sleep in Pregnant Women.
AB  - STUDY OBJECTIVES: To assess whether daytime naps negatively impact nocturnal
      sleep. DESIGN: Longitudinal, prospective cohort design. PARTICIPANTS: 161
      pregnant women recruited and evaluated in early gestation (10-20 weeks).
      MEASUREMENTS AND RESULTS: Daily sleep information was collected in three 2-week
      periods (10-12, 14-16, and 18-20 weeks gestation) with a daily sleep diary and an
      actigraph. The average number of naps, as well as the average length of each nap,
      were calculated from sleep diaries. Women were categorized first as non nappers
      (0 naps/2-week period), moderate nappers (1-3 naps/2-week period), or frequent
      nappers (>= 4 naps/2-week period). Then, based on the average nap length, they
      were categorized as short (< 90 min) or long (>= 90 min) nappers. Nocturnal sleep
      parameters included SOL, WASO, SE, and TST. SAS procedure MIXED was used for
      modeling the main effects of nap group and time, and time by nap group
      interactions. Women who took naps had a decrease in diary-assessed nocturnal TST,
      but not actigraphy-assessed TST. This observation was group- and time-specific.
      There were no other group differences. Women who napped >= 90 min had poorer
      diary-assessed SE and lower diary-assessed TST than those who took shorter naps.
      Length of nap was not associated with any other sleep measures. CONCLUSIONS: The
      number of daytime naps have minimal impact on nocturnal sleep parameters;
      however, long nappers did exhibit modestly impaired sleep continuity and sleep
      quality. Overall, we propose that daytime naps provide a beneficial
      countermeasure to the sleep disruption commonly reported by pregnant women. This
      may be clinically beneficial given that sleep continuity and quality are
      important correlates of pregnancy outcomes. COMMENTARY: A commentary on this
      article appears in this issue on page 593.

PMID- 25766713
TI  - Noninvasive ventilation improves sleep in amyotrophic lateral sclerosis: a
      prospective polysomnographic study.
AB  - STUDY OBJECTIVE: To evaluate the effects of noninvasive ventilation (NIV) on
      sleep in patients with amyotrophic lateral sclerosis (ALS) after meticulous
      titration with polysomnography (PSG). METHODS: In this prospective observational
      study, 24 ALS patients were admitted to the sleep laboratory during 4 nights for
      in-hospital NIV titration with PSG and nocturnal capnography. Questionnaires were
      used to assess subjective sleep quality and quality of life (QoL). Patients were
      readmitted after one month. RESULTS: In the total group, slow wave sleep and REM
      sleep increased and the arousal-awakening index improved. The group without
      bulbar involvement (non-bulbar) showed the same improvements, together with an
      increase in sleep efficiency. Nocturnal oxygen and carbon dioxide levels improved
      in the total and non-bulbar group. Except for oxygen saturation during REM sleep,
      no improvement in respiratory function or sleep structure was found in bulbar
      patients. However, these patients showed less room for improvement. Patient
      reported outcomes showed improvement in sleep quality and QoL for the total and
      non-bulbar group, while bulbar patients only reported improvements in very few
      subscores. CONCLUSIONS: This study shows an improvement of sleep architecture,
      carbon dioxide, and nocturnal oxygen saturation at the end of NIV titration and
      after one month of NIV in ALS patients. More studies are needed to identify the
      appropriate time to start NIV in bulbar patients. Our results suggest that
      accurate titration of NIV by PSG improves sleep quality. COMMENTARY: A commentary
      on this article appears in this issue on page 511.

PMID- 25766714
TI  - Sleep Disturbances in Pediatric Chronic Fatigue Syndrome: A Review of Current
      Research.
AB  - OBJECTIVE: Children and adolescents with chronic fatigue syndrome (CFS)
      frequently report sleep disturbances. However, little is known about the nature
      and severity of sleep disturbance and factors associated with sleep problems in
      pediatric CFS. The purpose of this review was to synthesize and critically
      appraise existing literature relating to sleep disturbances in pediatric CFS.
      METHODS: Embase, CINAHL, PsychINFO, PubMed. and Medline databases were searched
      to retrieve all studies that included an assessment of sleep in pediatric CFS.
      Two reviewers independently assessed eligibility, extracted data, and
      systematically assessed reporting quality. RESULTS: Six studies were included and
      these were mostly case-controlled designs. Findings varied across studies;
      however, most studies found that children and adolescents with CFS had
      significantly more sleep disturbances when compared to healthy controls.
      Significant methodological variations and limitations were apparent. CONCLUSIONS:
      This review suggests that children and adolescents with CFS experience sleep
      disturbances. However, results need to be interpreted cautiously given the
      limited evidence available and its overall low quality. More research is required
      to elucidate the nature and extent of sleep disturbance in pediatric CFS and
      should focus on (1) identifying the specific types, causes, and severity of sleep
      disturbances; (2) the specific consequences of sleep disturbances; and (3) the
      most effective interventions for sleep problems in this population.

PMID- 25766715
TI  - Obstructive Sleep Apnea in Obese Hospitalized Patients: A Single Center
      Experience.
AB  - STUDY OBJECTIVES: Obstructive sleep apnea (OSA) is an important health problem
      associated with significant morbidity and mortality. This condition often is
      underrecognized in hospitalized patients. The aim of this study was to conduct a
      clinical pathway evaluation (CPE) among obese patients admitted to a tertiary
      care hospital. We also assessed oxygen desaturation index (ODI, measured by
      overnight pulse oximetry) as a potential low-cost screening tool for identifying
      OSA. METHODS: This was a prospective study of 754 patients admitted to an
      academic medical center between February 2013 and February 2014. Consecutive
      obese patients (body mass index >= 30) admitted to the hospital (medical
      services) were screened and evaluated for OSA with the snoring, tiredness during
      daytime, observed apnea, high blood pressure (STOP) questionnaire. The admitting
      team was advised to perform follow-up evaluation, including polysomnography, if
      the test was positive. RESULTS: A total of 636 patients were classified as high
      risk and 118 as low risk for OSA. Within 4 w of discharge, 149 patients underwent
      polysomnography, and of these, 87% (129) were shown to have OSA. An optimal
      screening cutoff point for OSA (apnea-hypopnea index >= 10/h) was determined to
      be ODI >= 10/h [Matthews correlation coefficient = 0.36, 95% confidence interval
      = 0.24-0.47]. Significantly more hospitalized patients were identified and
      underwent polysomnography compared with the year prior to introduction of the
      CPE. CONCLUSIONS: Our results indicate that the CPE increased the identification
      of OSA in this population. Furthermore, ODI derived from overnight pulse oximetry
      may be a cost-effective strategy to screen for OSA in hospitalized patients.

PMID- 25766716
TI  - Identifying Insomnia in Early Pregnancy: Validation of the Insomnia Symptoms
      Questionnaire (ISQ) in Pregnant Women.
AB  - STUDY OBJECTIVES: Although a substantial number of pregnant women report symptoms
      of insomnia, few studies have used a validated instrument to determine the
      prevalence in early gestation. Identification of insomnia in pregnancy is vital
      given the strong connection between insomnia and the incidence of depression,
      cardiovascular disease, or immune dysregulation. The goal of this paper is to
      provide additional psychometric evaluation and validation of the Insomnia Symptom
      Questionnaire (ISQ) and to establish prevalence rates of insomnia among a cohort
      of pregnant women during early gestation. METHODS: The ISQ was evaluated in 143
      pregnant women at 12 weeks gestation. The internal consistency and criterion
      validity of the dichotomized ISQ were compared to traditional measures of sleep
      from sleep diaries, actigraphy, and the Pittsburgh Sleep Quality Index using
      indices of sensitivity, specificity, positive and negative predictive value (PPV,
      NPV), and likelihood ratio (LR) tests. RESULTS: The ISQ identified 12.6% of the
      sample as meeting a case definition of insomnia, consistent with established
      diagnostic criteria. Good reliability was established with Cronbach alpha = 0.86.
      The ISQ had high specificity (most > 85%), but sensitivity, PPV, NPV, and LRs
      varied according to which sleep measure was used as the validating criterion.
      CONCLUSIONS: Insomnia is a health problem for many pregnant women at all stages
      in pregnancy. These data support the validity and reliability of the ISQ to
      identify insomnia in pregnant women. The ISQ is a short and cost-effective tool
      that can be quickly employed in large observational studies or in clinical
      practice where perinatal women are seen. COMMENTARY: A commentary on this article
      appears in this issue on page 593.

PMID- 25766717
TI  - Improved Sleep Quality is Associated with Reductions in Depression and PTSD
      Arousal Symptoms and Increases in IGF-1 Concentrations.
AB  - STUDY OBJECTIVES: One-third of deployed military personnel will be diagnosed with
      insomnia, placing them at high risk for comorbid depression, posttraumatic stress
      disorder (PTSD), and medical conditions. The disruption of trophic factors has
      been implicated in these comorbid conditions, which can impede postdeployment
      recovery. This study determined if improved sleep quality is associated with (1)
      reductions in depression and posttraumatic symptoms, as well as enrichments in
      health-related quality of life (HRQOL), and (2) changes in plasma concentrations
      of brain derived neurotrophic factor (BDNF) and insulin-like growth factor-1 (IGF
      1). METHODS: Forty-four military personnel diagnosed with insomnia underwent
      clinical evaluations and blood draws at pretreatment and at posttreatment
      following cognitive behavioral therapy for insomnia and automatic positive airway
      pressure treatment. Participants were classified as sleep improved (n = 28) or
      sleep declined (n = 16) based on their change in pretreatment to posttreatment
      Pittsburgh Sleep Quality Index (PSQI) score. Both groups were compared on
      outcomes of depression, PTSD, HRQOL, BDNF, and IGF-1. RESULTS: Paired t-tests of
      the sleep improved group revealed significant declines in depression (p = 0.005)
      and posttraumatic arousal (p = 0.006) symptoms, and a significant increase in
      concentrations of IGF-1 (p = 0.009). The sleep declined group had no relevant
      change in psychiatric symptoms or trophic factors, and had further declines on
      five of eight dimensions of HRQOL. Between-group change score differences were
      significant at p < 0.05. CONCLUSIONS: These findings suggest that interventions,
      which successfully improve sleep quality, are an effective means to reduce the
      depression and posttraumatic arousal symptoms common to military personnel, as
      well as increase protective trophic factors implicated in these conditions.

PMID- 25766718
TI  - Long-Term Effectiveness and Safety of Maxillomandibular Advancement for Treatment
      of Obstructive Sleep Apnea.
AB  - STUDY OBJECTIVE: To determine the long-term clinical effectiveness and safety of
      maxillomandibular advancement (MMA) for the treatment of moderate to severe
      obstructive sleep apnea (OSA). METHODS: A prospective two-center cohort study
      design was used to evaluate OSA patients who underwent MMA > 2 years ago. The
      primary outcome measure was the apnea-hypopnea index (AHI). Secondary outcome
      measures included blood pressure (BP), sleepiness (Epworth Sleepiness Scale
      [ESS]), and quality of life (Functional Outcomes of Sleep Questionnaire [FOSQ]).
      RESULTS: 30 adult patients (80% men, age 50.5 +/- 9.6 years [mean +/- SD])
      participated in the study. The AHI decreased from a mean of 49 to 10.9 events/h
      (p < 0.0001) at the time of long-term evaluation (6.6 +/- 2.8 years after MMA),
      with 46.7% of patients obtaining an AHI < 5 and 83.4% of patients attaining an
      AHI <= 15 events/h. The mean diastolic BP decreased from 83.7 to 79.0 mm Hg (p <
      0.05). ESS decreased from a mean of 12.1 to 6.0 (p < 0.01). FOSQ increased from a
      mean of 12.6 to 17.3 (p < 0.05). Few long-term treatment-related adverse events
      occurred, which had minimal impact on quality of life (QOL). CONCLUSIONS: MMA is
      a clinically effective and safe long-term treatment for most patients with
      moderate-to-severe OSA as demonstrated by significant decreases in AHI, diastolic
      BP, and subjective sleepiness, with concomitant significant improvements in QOL.
      The results of this small cohort study suggest that MMA should be considered as
      the alternative treatment of choice for patients with severe OSA who cannot fully
      adhere to CPAP therapy.

PMID- 25766719
TI  - Is There a Clinical Role For Smartphone Sleep Apps? Comparison of Sleep Cycle
      Detection by a Smartphone Application to Polysomnography.
AB  - STUDY OBJECTIVES: Several inexpensive, readily available smartphone apps that
      claim to monitor sleep are popular among patients. However, their accuracy is
      unknown, which limits their widespread clinical use. We therefore conducted this
      study to evaluate the validity of parameters reported by one such app, the Sleep
      Time app (Azumio, Inc., Palo Alto, CA, USA) for iPhones. METHODS: Twenty
      volunteers with no previously diagnosed sleep disorders underwent in-laboratory
      polysomnography (PSG) while simultaneously using the app. Parameters reported by
      the app were then compared to those obtained by PSG. In addition, an epoch-by
      epoch analysis was performed by dividing the PSG and app graph into 15-min
      epochs. RESULTS: There was no correlation between PSG and app sleep efficiency (r
      = -0.127, p = 0.592), light sleep percentage (r = 0.024, p = 0.921), deep sleep
      percentage (r = 0.181, p = 0.444) or sleep latency (rs = 0.384, p = 0.094). The
      app slightly and nonsignificantly overestimated sleep efficiency by 0.12% (95%
      confidence interval [CI] -4.9 to 5.1%, p = 0.962), significantly underestimated
      light sleep by 27.9% (95% CI 19.4-36.4%, p < 0.0001), significantly overestimated
      deep sleep by 11.1% (CI 4.7-17.4%, p = 0.008) and significantly overestimated
      sleep latency by 15.6 min (CI 9.7-21.6, p < 0.0001). Epochwise comparison showed
      low overall accuracy (45.9%) due to poor interstage discrimination, but high
      accuracy in sleep-wake detection (85.9%). The app had high sensitivity but poor
      specificity in detecting sleep (89.9% and 50%, respectively). CONCLUSIONS: Our
      study shows that the absolute parameters and sleep staging reported by the Sleep
      Time app (Azumio, Inc.) for iPhones correlate poorly with PSG. Further studies
      comparing app sleep-wake detection to actigraphy may help elucidate its potential
      clinical utility. COMMENTARY: A commentary on this article appears in this issue
      on page 695.

PMID- 25766721
TI  - Why many semiempirical molecular orbital theories fail for liquid water and how
      to fix them.
AB  - Water is an extremely important liquid for chemistry and the search for more
      accurate force fields for liquid water continues unabated. Neglect of diatomic
      differential overlap (NDDO) molecular orbital methods provide and intriguing
      generalization of classical force fields in this regard because they can account
      both for bond breaking and electronic polarization of molecules. However, we show
      that most standard NDDO methods fail for water because they give an incorrect
      description of hydrogen bonding, water's key structural feature. Using force
      matching, we design a reparameterized NDDO model and find that it qualitatively
      reproduces the experimental radial distribution function of water, as well as
      various monomer, dimer, and bulk properties that PM6 does not. This suggests that
      the apparent limitations of NDDO models are primarily due to poor
      parameterization and not to the NDDO approximations themselves. Finally, we
      identify the physical parameters that most influence the condensed phase
      properties. These results help to elucidate the chemistry that a semiempirical
      molecular orbital picture of water must capture. We conclude that properly
      parameterized NDDO models could be useful for simulations that require
      electronically detailed explicit solvent, including the calculation of redox
      potentials and simulation of charge transfer and photochemistry.

PMID- 25766720
TI  - Retrospective Assessment of Home Ventilation to Reduce Rehospitalization in
      Chronic Obstructive Pulmonary Disease.
AB  - BACKGROUND: Healthcare systems are attempting to reduce hospital readmissions due
      to chronic obstructive pulmonary disease (COPD). METHODS: A retrospective study
      of a quality improvement (QI) program performed at a single center whose
      multifaceted intervention included nocturnal administration of advanced positive
      airway pressure (PAP) modality (or noninvasive positive pressure ventilation
      [NIPPV]) called averaged volume assured pressure support (AVAPS-AE) initiation by
      a respiratory therapist (RT), medication reconciliation by a pharmacist, adequate
      provision of oxygen, and ongoing RT-led care. In this QI program, consecutive
      patients who had been hospitalized twice in a single year with an acute COPD
      exacerbation underwent such interventions after they met specific selection
      criteria. RESULTS: Three-hundred ninety-seven consecutive patients were eligible
      for the program because they had two or more hospitalizations in the previous
      year. The proportion of patients who were readmitted on two or more occasions
      decreased from 100% (397 of 397) in the year prior to initiation of intervention
      to 2.2% (9 of 397) in the following year (chi(2) = 758, p < 0.0001). Seventy
      patients died over the one year following initiation of the multifaceted
      intervention. A composite outcome of rehospitalization and death was associated
      with inhaled steroids (adjusted odds ratio [adjOR] of 2.13; 95% confidence
      interval [CI] 1.09, 4.17; p = 0.02), whereas inhaled antimuscarinics tended to be
      associated with less risk for rehospitalization or death (adjOR 0.56; 95% CI
      0.34, 1.03; p = 0.06). CONCLUSION: In a retrospective cohort study of a QI
      initiative undertaken at a single center, we have observed that a multifaceted
      intervention that involved initiation of nocturnal advanced PAP (NIPPV) modality,
      RT-led respiratory care, medication reconciliation, appropriate oxygen therapy
      initiation, and patient education led to significant reduction in
      rehospitalization.

PMID- 25766722
TI  - Exceptional Response to Pazopanib in a Patient with Urothelial Carcinoma
      Harboring FGFR3 Activating Mutation and Amplification.

PMID- 25766723
TI  - Prostate-specific antigen pox virus vaccination for recurrent prostate cancer.

PMID- 25766726
TI  - Palladium-catalyzed oxidative C-H/C-H cross-coupling of 1-substituted 1,2,3
      triazoles with furans and thiophenes.
AB  - Palladium-catalyzed heteroarylation of 1-substituted 1,2,3-triazoles with furans
      and thiophenes has been developed in the presence of pyridine and Ag2CO3. The
      procedure is suitable for the regioselective preparation of 1,5-disubstituted
      1,2,3-triazoles through conventional heating at reaction temperatures of 90-100 
      degrees C for 18 h. 

PMID- 25766724
TI  - Phase 3 study of nilotinib vs imatinib in Chinese patients with newly diagnosed
      chronic myeloid leukemia in chronic phase: ENESTchina.
AB  - Treatment with a tyrosine kinase inhibitor (TKI) targeting BCR-ABL1 is currently
      the standard of care for patients with chronic myeloid leukemia (CML) in chronic
      phase (CML-CP). In this study, we present results of the ENESTchina (Evaluating
      Nilotinib Efficacy and Safety in Clinical Trials-China) that was conducted to
      investigate nilotinib 300 mg twice daily vs imatinib 400 mg once daily in a
      Chinese population. ENESTchina met its primary end point with a statistically
      significant higher rate of major molecular response (MMR; BCR-ABL1 <=0.1% on the
      International Scale) at 12 months in the nilotinib arm vs the imatinib arm (52.2%
      vs 27.8%; P < .0001), and MMR rates remained higher with nilotinib vs imatinib
      throughout the follow-up period. Rates of complete cytogenetic response (0%
      Philadelphia chromosome-positive [Ph+] metaphases by standard cytogenetics) were
      comparable and >=80% by 24 months in both arms. The estimated rate of freedom
      from progression to accelerated phase/blast crisis at 24 months was 95.4% in each
      arm. The safety profiles of both drugs were similar to those from previous
      studies. In conclusion, rates of MMR at 12 months were superior with nilotinib vs
      imatinib in Chinese patients with newly diagnosed Ph+ CML-CP. This trial was
      registered at www.clinicaltrials.gov as #NCT01275196. 

PMID- 25766725
TI  - Allogeneic HY antibodies detected 3 months after female-to-male HCT predict
      chronic GVHD and nonrelapse mortality in humans.
AB  - Allogeneic antibodies against minor histocompatibility antigens encoded on the Y
      chromosome (HY-Abs) develop after hematopoietic cell transplant (HCT) of male
      recipients with female donors (F->M). However, the temporal association between
      HY-Ab development and chronic graft-versus-host disease (cGVHD) has yet to be
      elucidated. We studied 136 adult F->M HCT patients, with plasma prospectively
      collected through 3 years posttransplant, and measured immunoglobulin G against 6
      H-Y antigens. Multiple HY-Abs were frequently detected beginning at 3 months
      posttransplant: 78 (57%) of F->M patients were seropositive for at least 1 of the
      6 HY-Abs, and 3-month seropositivity for each HY-Ab was associated with a
      persistent seropositive response throughout the posttransplant follow-up period
      (P < .001 in each). There were no associations between pretransplant features and
      3-month overall HY-Ab development. Detection of multiple HY-Abs at 3 months
      (represented by HY score) was significantly associated with an increased risk of
      cGVHD (P < .0001) and nonrelapse mortality (P < .01). Compared to clinical
      factors alone, the addition of HY score to clinical factors improved the
      predictive potential of cGVHD (P < .01). Monitoring HY-Ab development thus
      stratifies cGVHD risk in F->M HCT patients and may support preemptive prophylaxis
      therapy for cGVHD beginning at 3 months posttransplant.

PMID- 25766727
TI  - Comparison of automated breast ultrasonography to handheld ultrasonography in
      detecting and diagnosing breast lesions.
AB  - BACKGROUND: Automated breast ultrasonography (ABUS) is increasingly used as a
      screening tool. Several studies have demonstrated a similar diagnostic
      performance for ABUS compared with handheld ultrasonography (HHUS), but the
      overall results have been controversial. PURPOSE: To compare the clinical utility
      of ABUS and HHUS for detection and diagnosis of breast lesions. MATERIAL AND
      METHODS: ABUS and HHUS images of suspicious breast lesions were obtained for 173
      consecutive women scheduled to undergo ultrasonography (US)-guided or
      stereotactic biopsy. There were a total of 206 lesions, 46 of which were
      malignant and 160 benign. Three breast radiologists took part in this study: two
      reviewed the ABUS images, and the third reviewed all of the images, ABUS and
      HHUS, as well as the patients' medical records. The biopsied-lesion-detection
      rates were obtained. Using the Breast Imaging Reporting and Data System (BI
      RADS), the images of the biopsied lesions were evaluated. Factors affecting ABUS
      detectability were analyzed. RESULTS: The overall detection rates were 83.0% for
      ABUS and 94.2% for HHUS. Ten lesions were not detected on either HHUS or ABUS and
      these were microcalcifications (one malignancy and nine benign lesions). Of the
      194 HHUS-detected lesions, 169 were detected by ABUS and 25 benign were not. ABUS
      less frequently detected lesions of smaller size as well as those of benign
      appearance and lower final-assessment category (P = 0.011 and P < 0.0001,
      respectively). CONCLUSION: ABUS detected all of the malignant lesions that were
      detected on HHUS. ABUS missed several smaller benign lesions.

PMID- 25766728
TI  - Cardiac MRI in patients with cardiac pacemakers: practical methods for reducing
      susceptibility artifacts and optimizing image quality.
AB  - BACKGROUND: Magnetic resonance imaging (MRI) of pacemaker patients has become
      available despite of previous contraindications. However, pacing systems
      containing ferromagnetic material may hamper the diagnostic quality of cardiac MR
      (CMR) images. PURPOSE: To study methods for reducing susceptibility-based
      artifacts in CMR examinations of pacemaker patients. MATERIAL AND METHODS:
      Altogether 16 patients were scanned with 1.5T MRI scanner using cine balanced
      steady-state free-precession (bSSFP) and spoiled gradient echo (SPGR) sequences.
      The use of frequency-scout was also evaluated. For myocardial late gadolinium
      enhanced (LGE) imaging, SPGR or bSSFP readout inversion-recovery prepared
      gradient echo sequences were used with and without phase-sensitive inversion
      recovery (PSIR). Two radiologists subjectively compared the image quality (IQ)
      and the ranges of susceptibility artifacts were evaluated objectively. RESULTS:
      The IQ proved adequate for diagnosing each patient, although in a few patients
      with a left-side implanted generator, artifacts hampered IQ in the anterior and
      anteroseptal segments of the myocardium in bSSFP cine and LGE sequences. In bSSFP
      cine, the use of frequency-scout could often transfer the banding artifacts away
      from the left ventricular myocardium. In LGE imaging, the artifacts were more
      pronounced in IR-bSSFP and PSIR than in IR-SPGR sequences. The ranges of
      generator-based artifacts were greater in bSSFP (10-12 cm) than in SPGR (6 cm)
      sequences due to banding artifacts. CONCLUSION: The artifacts caused by
      pacemakers typically did not compromise the diagnostic IQ. The use of frequency
      scout prior to bSSFP cine or the use of SPGR-based sequences could also improve
      IQ.

PMID- 25766730
TI  - Systematic regionalization of stroke care.

PMID- 25766729
TI  - High 18F-FDG uptake in PMAH correlated with normal expression of Glut1, HK1, HK2,
      and HK3.
AB  - BACKGROUND: Primary macronodular adrenal hyperplasia (PMAH) is a rare cause of
      Cushing's syndrome, characterized by functioning adrenal macronodules and
      variable cortisol production. Recently, we demonstrated a high 18F-FDG uptake in
      PMAH, an unexpected finding for a benign disorder. PURPOSE: To investigate
      whether there is a correlation between 18F-FDG high uptake and the expression
      levels of the glycolytic pathway components GLUT1, HK1, HK2, and HK3 in PMAH.
      MATERIAL AND METHODS: We selected 12 patients undergoing surgery for PMAH who had
      preoperatively undergone 18F-FDG PET/CT. mRNA and protein expression of the
      selected genes were evaluated in the adrenal nodules from patients who underwent
      surgery through quantitative RT-PCR and by immunohistochemistry, respectively.
      RESULTS: SUVmax in PMAH was in the range of 3.3-8.9 and the adrenal size was in
      the range of 3.5-15 cm. A strong correlation between 18F-FDG uptake and largest
      adrenal diameter was observed in patients with PMAH. However, no correlation
      between 18F-FDG uptake and GLUT1, HK1, HK2, HK3 mRNA, and protein expression was
      observed. CONCLUSION: High 18F-FDG uptake is observed in the majority of PMAH
      cases. However, 18F-FDG uptake in PMAH is independent of the expression levels of
      GLUT1, HK1, HK2, and HK3. Further investigation is required to elucidate the
      molecular mechanisms underlying increased 18F-FDG uptake in PMAH.

PMID- 25766731
TI  - Effects of a family-assisted smoking cessation intervention based on motivational
      interviewing among low-motivated smokers in China.
AB  - OBJECTIVE: To test the efficacy of a family-assisted smoking cessation
      intervention based on Motivational interviewing (MI) among low-motivated Chinese
      smokers. METHODS: A two-armed randomized controlled trial study design was
      utilized. 159 Smoker-supporter pairs were randomly allocated to the intervention
      (a family-assisted MI intervention-77) or control (an intensity-matched health
      education-82) group (IG & CG). Change in smoking characteristics, communication
      characteristics, Partner Intervention Questionnaire (PIQ), Decisional Balance
      Scale (DBL), and Situational Temptations Scale (STP) were measured at baseline,
      post-intervention, 3-month and 6-month follow-up. RESULTS: Compared to CG, IG had
      more significant increase over time in self-report quitting attempts of at least
      24h, biochemically verified 7-day smoking abstinence, the Positive dimension of
      PIQ and the Cons in DBL, whereas the daily cigarettes smoked, the Pros in DBL and
      STP were showed more significant decrease over time in IG (P<0.05). After
      intervention, the communication frequency and satisfactory were also improved by
      smokers (P<0.01). CONCLUSION: The family-assisted MI intervention is more
      effective in changing the smoking behaviors and increasing the communication
      between smokers and family, than health education. PRACTICAL IMPLICATIONS: Using
      the family-assisted smoking cessation intervention based on MI, community health
      service providers can influence and empower low-motivated smokers positively for
      quit smoking.

PMID- 25766732
TI  - Quality of radiologists' communication with other clinicians--As experienced by
      radiologists.
AB  - OBJECTIVE: The objective was to study radiologists' experiences of written and
      oral communication with referring clinicians, and its potential implications for
      decision making and patient care. METHODS: Focus group discussions with 12
      radiologists were carried out. Content analysis was used for interpretation of
      the data. RESULTS: Radiologists reported many problems with the request forms:
      improper choice of imaging examinations and procedures, insufficient patient
      history/information, unclear clinical questions, lack of specific terms and
      unclear abbreviations on the request form. Radiologists also mentioned other
      difficulties: insufficient attention among participating clinicians during
      conferences, difficulties in reaching the referring clinicians by telephone, and
      communication difficulties in making priorities between patients. To overcome
      these problems, radiologists suggested increased contacts between radiologists
      and clinicians, and educational activities. CONCLUSION: A number of difficulties
      in oral and written communication were highlighted. The use of medical imaging
      may be optimized by joint discussions on indications and methodology and
      educational activities, such as lectures, seminars and conferences, directed to
      the medical community at large. PRACTICE IMPLICATIONS: Improved communication
      between radiologists and referring clinicians should be encouraged to ensure
      diagnostic quality, correct patient prioritization and patient safety, and to
      avoid unnecessary delays and costs.

PMID- 25766733
TI  - Comparison of Intraoperative Aberrometry, OCT-Based IOL Formula, Haigis-L, and
      Masket Formulae for IOL Power Calculation after Laser Vision Correction.
AB  - PURPOSE: To compare the accuracy of intraoperative aberrometry technology and the
      Fourier-domain optical coherence tomography (OCT)-based intraocular lens (IOL)
      formula for IOL power calculation in eyes undergoing cataract surgery after
      previous laser vision correction (LVC) compared with established methods. DESIGN:
      Retrospective consecutive case series. PARTICIPANTS: Patients undergoing cataract
      surgery with a history of LASIK or photorefractive keratectomy. METHODS: The IOL
      power was estimated preoperatively using the IOLMaster 500 (Carl Zeiss Meditec,
      Dublin, CA) to calculate the Haigis-L and Masket regression formulae (when prior
      data were available), and the Optovue RTVue (Optovue Inc, Fremont, CA) spectral
      domain OCT was used to obtain the Fourier-domain OCT-based IOL formula. The
      Optiwave Refractive Analysis (ORA) System (WaveTec Vision Systems Inc, Aliso
      Viejo, CA) wavefront aberrometer measured aphakic refractive measurements
      intraoperatively and calculated the IOL power with a modified vergence formula.
      Comparative analysis was done for predictive accuracy of IOL power determination
      using 2 conventional methods and 2 new technologies: the Haigis-L formula, Masket
      regression formula, ORA intraoperative aberrometry, and Optovue RTVue Fourier
      domain OCT-based IOL formula. Patients without historical data (N = 39) were
      compared using 3 methods (Haigis-L, ORA, and Optovue), and patients with
      historical data (N = 20) were compared using all methods (Masket regression
      formula, Haigis-L, ORA, and Optovue). MAIN OUTCOME MEASURES: Median absolute
      error (MedAE), mean absolute error (MAE), and percentage of eyes within +/-0.25,
      +/-0.50, +/-0.75, and +/-1.00 diopters (D) of refractive prediction error.
      RESULTS: A total of 39 eyes of 29 patients without historical data were analyzed
      separately from 20 eyes of 20 patients with historical data. In the group without
      historical data (N = 39), 49% of eyes were within +/-0.25 D, 69% to 74% of eyes
      were within +/-0.50 D, 87% to 97% of eyes were within +/-0.75 D, and 92% to 97%
      of eyes were within +/-1.00 D of targeted refractive IOL power prediction error.
      The MedAE was 0.26 D for Haigis-L, 0.29 D for ORA, and 0.28 D for Optovue. The
      MAE was 0.37 D for Haigis-L, 0.34 D for ORA, and 0.39 D for Optovue. In the group
      with historical data (N = 20), 35% to 70% of eyes were within +/-0.25 D, 60% to
      85% of eyes were within +/-0.50 D, 80% to 95% of eyes were within +/-0.75 D, and
      90% to 95% of eyes were within +/-1.00 D of targeted refractive IOL power
      prediction error. The MedAE was 0.21 D for the Masket regression formula, 0.22 D
      for the Haigis-L formula, 0.25 D for ORA, and 0.39 for Optovue. The MAE was 0.28
      D for the Masket regression formula, 0.31 D for the Haigis-L formula, 0.37 D for
      ORA, and 0.44 D for Optovue. There was no statistically significant difference
      among the methods. CONCLUSIONS: Newer technology to estimate IOL power
      calculations in eyes after LVC shows promising results when compared with
      established methods.

PMID- 25766734
TI  - The origins of vestibular science.
AB  - The vestibular system conveys information about body motion and gravity. It was
      one of the first sensory systems to emerge in evolution; however, it was also the
      last to be discovered. The causal relationship between diseases of the ear and
      the symptom of vertigo was not recognized until the mid-19th century. Only a few
      years later, the basic principle of semicircular canal function was elucidated
      almost simultaneously by three scientists with completely different backgrounds.
      This historical review describes the major milestones in the discoveries of the
      anatomy and the physiology of the vestibular system that paved the way for the
      establishment of neurotology as a clinical subspecialty. 

PMID- 25766735
TI  - Prevalence of antibiotic resistance in Escherichia coli isolated from urine
      samples routinely referred by general practitioners in a large urban centre in
      south-west England.

PMID- 25766736
TI  - Metagenomic analysis of the impact of nitrofurantoin treatment on the human
      faecal microbiota.
AB  - OBJECTIVES: The objective was to study changes in the faecal microbiota of
      patients with uncomplicated urinary tract infections (UTIs) treated with
      nitrofurantoin and of non-treated healthy controls using 16S rRNA analysis.
      METHODS: Serial stool samples were collected from patients receiving
      nitrofurantoin treatment at different timepoints [before treatment (day 1; T1),
      within 48 h of end of treatment (days 5-15; T2) and 28 days after treatment (days
      31-43; T3)], as well as from healthy controls. Direct DNA extraction (PowerSoil
      DNA Isolation Kit, MoBio Laboratories, Carlsbad, CA, USA) from stool samples was
      followed by pyrosequencing (454 GS FLX Titanium) of the V3-V5 region of the
      bacterial 16S rRNA gene. RESULTS: Among UTI patients, mean proportions of the
      Actinobacteria phylum increased by 19.6% in the first follow-up sample (T2) in
      comparison with the pretreatment baseline stool sample (T1) (P = 0.026). However,
      proportions of Actinobacteria reversed to 'normal' pre-antibiotic levels, with a
      mean difference of 1.0% compared with baseline proportions, in the second follow
      up sample (T3). The increase in Actinobacteria was specifically due to an
      increase in the Bifidobacteriaceae family (Bifidobacterium genus), which
      constituted 81.0% (95% CI +/-7.4%) of this phylum. CONCLUSIONS: No significant
      impact was observed other than a temporary increase in the beneficial
      Bifidobacterium genus following nitrofurantoin treatment, which supports its
      reintroduction into clinical use.

PMID- 25766737
TI  - Novel model-based dosing guidelines for gentamicin and tobramycin in preterm and
      term neonates.
AB  - OBJECTIVES: In the heterogeneous group of preterm and term neonates, gentamicin
      and tobramycin are mainly dosed according to empirical guidelines, after which
      therapeutic drug monitoring and subsequent dose adaptation are applied. In view
      of the variety of neonatal guidelines available, the purpose of this study was to
      evaluate target concentration attainment of these guidelines, and to propose a
      new model-based dosing guideline for these drugs in neonates. METHODS:
      Demographic characteristics of 1854 neonates (birth weight 390-5200 g, post-natal
      age 0-27 days) were extracted from earlier studies and sampled to obtain a test
      dataset of 5000 virtual patients. Monte Carlo simulations on the basis of
      validated models were undertaken to evaluate the attainment of target peak (5-12
      mg/L) and trough (<0.5 mg/L) concentrations, and cumulative AUC, with the
      existing and proposed guidelines. RESULTS: Across the entire neonatal age and
      weight range, the Dutch National Formulary for Children, the British National
      Formulary for Children, Neofax and the Red Book resulted in adequate peak but
      elevated trough concentrations (63%-90% above target). The proposed dosing
      guideline (4.5 mg/kg gentamicin or 5.5 mg/kg tobramycin) with a dosing interval
      based on birth weight and post-natal age leads to adequate peak concentrations
      with only 33%-38% of the trough concentrations above target, and a constant AUC
      across weight and post-natal age. CONCLUSIONS: The proposed neonatal dosing
      guideline for gentamicin and tobramycin results in improved attainment of target
      concentrations and should be prospectively evaluated in clinical studies to
      evaluate the efficacy and safety of this treatment.

PMID- 25766739
TI  - Visualising substrate-fingermark interactions: Solid-state NMR spectroscopy of
      amino acid reagent development on cellulose substrates.
AB  - Most spectroscopic studies of the reaction products formed by ninhydrin, 1,2
      indanedione-zinc (Ind-Zn) and 1,8-diazafluoren-9-one (DFO) when reacted with
      amino acids or latent fingermarks on paper substrates are focused on visible
      absorption or luminescence spectroscopy. In addition, structural elucidation
      studies are typically limited to solution-based mass spectrometry or liquid
      nuclear magnetic resonance (NMR) spectroscopy, which does not provide an accurate
      representation of the fingermark development process on common paper substrates.
      The research presented in this article demonstrates that solid-state carbon-13
      magic angle spinning NMR ((13)C-MAS-NMR) is a technique that can not only be
      utilised for structural studies of fingermark enhancement reagents, but is a
      promising technique for characterising the effect of paper chemistry on
      fingermark deposition and enhancement. The latter opens up a research area that
      has been under-explored to date but has the potential to improve our
      understanding of how fingermark secretions and enhancement reagents interact with
      paper substrates. 

PMID- 25766738
TI  - A competitive enzyme immunoassay for the quantitative detection of cocaine from
      banknotes and latent fingermarks.
AB  - A sensitive and versatile competitive enzyme immunoassay (cEIA) has been
      developed for the quantitative detection of cocaine in complex forensic samples.
      Polyclonal anti-cocaine antibody was purified from serum and deposited onto
      microtiter plates. The concentration of the cocaine antibody adsorbed onto the
      plates, and the dilution of the cocaine-HRP hapten were both studied to achieve
      an optimised immunoassay. The method was successfully used to quantify cocaine in
      extracts taken from both paper currency and latent fingermarks. The limit of
      detection (LOD) of 0.162ngmL(-1) achieved with the assay compares favourably to
      that of conventional chromatography-mass spectroscopy techniques, with an
      appropriate sensitivity for the quantification of cocaine at the low
      concentrations present in some forensic samples. The cEIA was directly compared
      to LC-MS for the analysis of ten UK banknote samples. The results obtained from
      both techniques were statistically similar, suggesting that the immunoassay was
      unaffected by cross-reactivity with potentially interfering compounds. The cEIA
      was used also for the detection of cocaine in extracts from latent fingermarks.
      The results obtained were compared to the cocaine concentrations detected in oral
      fluid sampled from the same individual. Using the cEIA, we have shown, for the
      first time, that endogeneously excreted cocaine can be detected and quantified
      from a single latent fingermark. Additionally, it has been shown that the
      presence of cocaine, at similar concentrations, in more than one latent
      fingermark from the same individual can be linked with those concentrations found
      in oral fluid. These results show that detection of drugs in latent fingermarks
      could directly indicate whether an individual has consumed the drug. The
      specificity and feasibility of measuring low concentrations of cocaine in complex
      forensic samples demonstrate the effectiveness and robustness of the assay. The
      immunoassay presents a simple and cost-effective alternative to the current mass
      spectrometry based techniques for the quantitation of cocaine at forensically
      significant concentrations. 

PMID- 25766740
TI  - The Relationship between Acidic Urinary pH and Overactive Bladder; Alkalization
      of Urine Improves the Symptoms of Overactive Bladder.
AB  - BACKGROUND: To determine association between urine pH and OAB symptoms and to
      determine if urinary alkalization improves overactive bladder (OAB) symptoms.
      METHODS: 659 patients with OAB were enrolled in this study between June 2012 and
      May 2014. 329 patients (group 1) were included in the final analysis. 201 adults
      were used as a control group (group 2). 24-hour urinary pH and the validated
      Turkish version of the OAB-V8 questionnaire were performed in patients. A 24-hour
      urine pH <6.2 was considered acidic urine. In the second part, a diet program was
      performed for 4 weeks in 30 participants. Urine pH values and OAB-V8 scoring
      results were recorded before the diet program and 2 and 4 weeks after the diet
      program. RESULTS: Acidic urinary pH was determined in 61.4% of patients with OAB.
      There was a significant association between the presence of acidic urine and OAB.
      Also, the OAB-V8 scores of patients were significantly higher in patients with
      acidic urine than nonacidic urine. OAB-V8 scores of patients showed statistically
      significant improvement after diet therapy (17.87 +/- 6.52 vs. 10.43 +/- 7.17; p
      < 0.001). CONCLUSIONS: We found that acidic urinary pH was closely associated
      with OAB, and alkalization of urine improved lower urinary tract symptoms. We
      suggest that urinary pH should be considered as a parameter in treatment planning
      of patients with OAB.

PMID- 25766742
TI  - Effect on Liver Enzymes of Biliopancreatic Diversion: 4 Years of Follow-Up.
AB  - BACKGROUND: Elevated serum aminotransferase levels are commonly associated with
      obesity and with a progression to chronic liver disease. Bariatric surgery is the
      most effective strategy to achieve weight loss. METHODS: We conducted the present
      study with the aim of evaluating the influence of biliopancreatic diversion (BPD)
      on liver enzymes levels during 4 years in morbid obese patients with normal
      aminotransferase (n = 65) and in morbid obese patients with high aminotransferase
      basal levels (n = 50). RESULTS: A decrease in alanine aminotransferase and
      aspartate aminotransferase activities was significant after biliopancreatic
      diversion. The basal percentage of high aminotransferase levels and percentage of
      ratio ALT/AST <1 also decreased significantly at 1-, 2-, 3- and 4-years of follow
      up in both groups. ALT (52 to 20%), AST (42 to 10%) and ALT/AST (80 to 22%) in
      patients with normal aminotransferase. ALT (82 to 20%), AST (70 to 6%) and
      ALT/AST (90 to 20%) in patients with elevated transaminase basal levels.
      Bariatric surgery was associated with a significant and sustained decrease in
      body weight in both groups. Serum trasnaminases level changes were positively
      correlated to body weight changes during follow-up. CONCLUSION: BPD is an
      effective method of achieving sustainable weight loss and reduced
      aminotransferase levels and enzyme ratios of liver damage.

PMID- 25766741
TI  - Horizontal transfer of a non-autonomous Helitron among insect and viral genomes.
AB  - BACKGROUND: The movement of mobile elements among species by horizontal
      transposon transfer (HTT) influences the evolution of genomes through the
      modification of structure and function. Helitrons are a relatively new lineage of
      DNA-based (class II) transposable elements (TEs) that propagate by rolling-circle
      replication, and are capable of acquiring host DNA. The rapid spread of Helitrons
      among animal lineages by HTT is facilitated by shuttling in viral particles or by
      unknown mechanisms mediated by close organism associations (e.g. between hosts
      and parasites). RESULTS: A non-autonomous Helitron independently annotated as
      BmHel-2 from Bombyx mori and the MITE01 element from Ostrinia nubilalis was
      predicted in the genomes of 24 species in the insect Order Lepidoptera.
      Integrated Helitrons retained >= 65% sequence identity over a 250 bp consensus,
      and were predicted to retain secondary structures inclusive of a 3'-hairpin and a
      5'-subterminal inverted repeat. Highly similar Hel-2 copies were predicted in the
      genomes of insects and associated viruses, which along with a previous documented
      case of real-time virus-insect cell line transposition suggests that this
      Helitron has likely propagated by HTT. CONCLUSIONS: These findings provide
      evidence that insect virus may mediate the HTT of Helitron-like TEs. This
      movement may facilitate the shuttling of DNA elements among insect genomes.
      Further sampling is required to determine the putative role of HTT in insect
      genome evolution.

PMID- 25766743
TI  - Nestin-expressing hair follicle-accessible pluripotent stem cells for nerve and
      spinal cord repair.
AB  - Nestin-expressing stem cells of the hair follicle, discovered by our laboratory,
      have been shown to be able to form neurons and other nonfollicle cell types. We
      have shown that the nestin-expressing stem cells from the hair follicle can
      effect the repair of peripheral nerve and spinal cord injury. The hair follicle
      stem cells differentiate into neuronal and glial cells after transplantation to
      the injured peripheral nerve and spinal cord, and enhance injury repair and
      locomotor recovery. We have termed these cells hair follicle-accessible
      pluripotent (HAP) stem cells. When the excised hair follicle with its nerve stump
      was placed in Gelfoam 3D histoculture, HAP stem cells grew and extended the hair
      follicle nerve which consisted of betaIII-tubulin-positive fibers with F-actin
      expression at the tip. These findings indicate that betaIII-tubulin-positive
      fibers elongating from the whisker follicle sensory nerve stump were growing
      axons. The growing whisker sensory nerve was highly enriched in HAP stem cells,
      which appeared to play a major role in its elongation and interaction with other
      nerves in 3D Gelfoam histoculture, including the sciatic nerve, the trigeminal
      nerve, and the trigeminal nerve ganglion. Our results suggest that a major
      function of the HAP stem cells in the hair follicle is for growth of the follicle
      sensory nerve. HAP stem cells have critical advantages over embryonic stem cells
      and induced pluripotent stem cells in that they are highly accessible, require no
      genetic manipulation, are nontumorigenic, and do not present ethical issues for
      regenerative medicine.

PMID- 25766744
TI  - Magnetic interactions in BiFe0.5Mn0.5O3 films and BiFeO3/BiMnO3 superlattices.
AB  - The clear understanding of exchange interactions between magnetic ions in
      substituted BiFeO3 is the prerequisite for the comprehensive studies on magnetic
      properties. BiFe0.5Mn0.5O3 films and BiFeO3/BiMnO3 superlattices have been
      fabricated by pulsed laser deposition on (001) SrTiO3 substrates. Using
      piezoresponse force microscopy (PFM), the ferroelectricity at room temperature
      has been inferred from the observation of PFM hysteresis loops and electrical
      writing of ferroelectric domains for both samples. Spin glass behavior has been
      observed in both samples by temperature dependent magnetization curves and decay
      of thermo-remnant magnetization with time. The magnetic ordering has been studied
      by X-ray magnetic circular dichroism measurements, and Fe-O-Mn interaction has
      been confirmed to be antiferromagnetic (AF). The observed spin glass in
      BiFe0.5Mn0.5O3 films has been attributed to cluster spin glass due to Mn-rich
      ferromagnetic (FM) clusters in AF matrix, while spin glass in BiFeO3/BiMnO3
      superlattices is due to competition between AF Fe-O-Fe, AF Fe-O-Mn and FM Mn-O-Mn
      interactions in the well ordered square lattice with two Fe ions in BiFeO3 layer
      and two Mn ions in BiMnO3 layer at interfaces.

PMID- 25766745
TI  - Lung abscess as a complication of bronchial thermoplasty.
AB  - BACKGROUND: Bronchial thermoplasty (BT) is an emerging treatment modality for
      patients with difficult to treat asthma. It has been shown to be beneficial for
      symptom control and improves quality of life and reduces frequency of
      hospitalization. Safety data from the two major trials of BT indicate that
      patients who undergo these procedures are most likely to experience adverse
      respiratory events in the first six weeks post treatment. Lung abscess has never
      been reported as a direct complication of BT. In this case; we report a lung
      abscess as an immediate complication of BT, which we believe may be the first
      case. CASE PRESENTATION: We describe a forty three year old Caucasian female
      presented three days post-bronchial thermoplasty with left sided chest pain
      radiating to the back associated with shortness of breath, wheeze and dry cough.
      She had also started to feel hot and cold and generally unwell. CONCLUSION: It
      remains unclear why this patient developed a lung abscess so acutely post BT
      treatment. It is important that safety data continues to be collated and
      published as the procedure becomes more widely available with further long term
      follow-up in particular.

PMID- 25766746
TI  - Activation of Type I and Type III Interferons in Chronic Hepatitis C.
AB  - Infection with hepatitis C virus (HCV) results in chronic and progressive liver
      disease. Persistency rates add up to 85%. Despite recognition of the virus by the
      human host in peripheral blood and in the liver, immune response appears to be
      ineffective in clearing infection. The ability to spontaneously eradicate the
      virus as well as the outcome of infection upon therapy with human recombinant
      interferon-alpha (IFN-alpha) was found to correlate most closely with genetic
      variations within the region encoding the IFN-lambda genes, as revealed by genome
      wide association studies on main ethnic populations in 2009. This review
      summarizes the induction of type I and type III IFN genes and their effectors,
      the IFN-stimulated genes. It focusses on the in vivo situation in chronic HCV
      infection in man both in the peripheral blood compartment and in the liver. It
      also addresses the impact of genetic polymorphisms in the region of type III IFN
      genes on their activation. Finally, it discusses how antiviral drugs (i.e. IFN
      alpha, ribavirin and the direct-acting antivirals) may complementarily control
      the activation of endogenous IFNs and succeed in combatting infections.

PMID- 25766747
TI  - Bioactive compounds of Crocus sativus L. and their semi-synthetic derivatives as
      promising anti-Helicobacter pylori, anti-malarial and anti-leishmanial agents.
AB  - Crocus sativus L. is known in herbal medicine for the various pharmacological
      effects of its components, but no data are found in literature about its
      biological properties toward Helicobacter pylori, Plasmodium spp. and Leishmania
      spp. In this work, the potential anti-bacterial and anti-parasitic effects of
      crocin and safranal, two important bioactive components in C. sativus, were
      explored, and also some semi-synthetic derivatives of safranal were tested in
      order to establish which modifications in the chemical structure could improve
      the biological activity. According to our promising results, we virtually
      screened our compounds by means of molecular modeling studies against the main H.
      pylori enzymes in order to unravel their putative mechanism of action. 

PMID- 25766748
TI  - Palladium nanotubes formed by lipid tubule templating and their application in
      ethanol electrocatalysis.
AB  - Palladium nanotubes were fabricated by using lipid tubules as templates for the
      first time in a controlled manner. The positively charged lipid 1,2-dioleoyl-3
      trimethylammoniumpropane (DOTAP) was doped into lipid tubules to adsorb PdCl4 (2
      ) on the tubule surfaces for further reduction. The lipid tubule formation was
      optimized by studying the growing dynamics and ethanol/water ratio. The DOTAP
      doped tubules showed pH stability from 0 to 14, which makes them ideal templates
      for metal plating. The Pd nanotubes are open-ended with a tunable wall thickness.
      They exhibited good electrocatalytic performance in ethanol. Their
      electrochemically active surface areas were 6.5, 10.6, and 83.2 m(2)  g(-1) for
      Pd nanotubes with 77, 101, and 150 nm wall thickness, respectively. These Pd
      nanotubes have great potential in fuel cells. The method demonstrated also opens
      up a way to synthesize hollow metal nanotubes.

PMID- 25766749
TI  - Dialysate Lavage: An Alternative Solution for Reducing the Peritoneal
      Implantation of Poorly Differentiated Gastric Cancer Cells.
AB  - BACKGROUND: Peritoneal lavage after cancer surgery is performed to reduce
      microscopic residual tumors in the peritoneum. This study evaluated the effects
      and mechanism of dialysate lavage in reducing the peritoneal implantation of
      gastric cancer cells. METHODS: Gastric cancer cells (MKN45 or AGS) were cultured
      with 1.5% peritoneal dialysate (PD) or normal saline (NS) for 30 min. The in
      vitro cell susceptibility to dialysate, including cell proliferation, cell death,
      cleaved PARP expression, and mitochondrial membrane potential, was evaluated. A
      murine model for gastric cancer cell peritoneal seeding was established to test
      the effects of PD and NS lavage on animal survival and tumor growth. RESULTS: A
      significant decrease in cell proliferation in PD and NS (75.2 +/- 0.1 vs. 12.4 +/
      0.2% in MKN45, p = 0.009; 58.2 +/- 0.01 vs. 28.0 +/- 0.01% in AGS, p = 0.008),
      an increase in mitochondrial permeability transition (93.0 +/- 2.6 vs. 18.0 +/-
      2.9% in MKN45, p = 0.021; 86.8 +/- 4.6 vs. 47.7 +/- 10.2% in AGS, p < 0.001), and
      an increase in the expression of cleaved PARP and increased death (25.6 +/- 9.4
      vs. 16.9 +/- 5.3% in MKN45, p = 0.031; 39.5 +/- 5.1 vs. 20.9 +/- 3.9% in AGS, p =
      0.008) were recorded for gastric cancer cells separately exposed to PD and NS.
      Twenty-four days after inoculating MKN45 cells (5 * 10(6)/0.1 ml) in the
      peritoneal cavity, the average number of seeded tumors was 67.3 +/- 10.8, 92.3 +/
      6.0, and 29.2 +/- 16.7 (p = 0.032), and the total weight of tumors was 0.98 +/-
      0.21, 0.58 +/- 0.12, and 0.31 +/- 0.17 g (p = 0.008), respectively, for mice
      receiving sham operation, NS lavage, and PD lavage. The 45-day survival rate for
      the PD lavage group was 22% compared to 0% for the sham injection and NS lavage
      groups (p = 0.034). CONCLUSION: PD induced significant cytotoxicity in gastric
      cancer cells that was related to mitochondrial perturbation. The use of PD lavage
      was effective in reducing the peritoneal implantation of gastric cancers in a
      murine model.

PMID- 25766750
TI  - Cell wall metabolism of peaches and nectarines treated with UV-B radiation: a
      biochemical and molecular approach.
AB  - BACKGROUND: Ultra-violet B (UV-B) radiation has been shown to improve, at least
      in selected genotypes, both the health-promoting potential and the aesthetic
      properties of tomato and peach fruits during their post-harvest period. The
      effects of post-harvest UV-B treatment on the cell-wall metabolism of peaches and
      nectarines (Prunus persica L. Batsch) were assessed in this study. Three
      cultivars, Suncrest (melting flesh, MF) and Babygold 7 (non-melting flesh, NMF)
      peaches and Big Top (slow melting, SM) nectarine, differing in the
      characteristics of textural changes and softening during ripening, were analysed.
      RESULTS: The effects of UV-B differ in relation to the cultivar considered. In MF
      'Suncrest' fruit, UV-B treatment significantly reduced the loss of flesh firmness
      despite the slight increase in the presence and activity of endo
      polygalacturonase. The activity of exo-polygalacturonase increased as well, while
      endo-1,4-beta-D-glucanase/beta-D-glucosidase, beta-galactosidase and pectin
      methylesterase were substantially unaffected by the treatment. The UV-B-induced
      reduction of flesh softening was paralleled by the inhibition of PpExp gene
      transcription and expansin protein accumulation. The UV-B treatment did not
      induce differences in flesh firmness between control and UV-B-treated NMF
      'Babygold 7' and SM 'Big Top' fruit. CONCLUSION: Based on these results, post
      harvest UV-B treatment may be considered a promising tool to improve shelf-life
      and quality of peach fruit.

PMID- 25766751
TI  - Nutritional or pharmacological activation of HCA(2) ameliorates
      neuroinflammation.
AB  - Neuroinflammation is a pathology common to many neurological diseases, including
      multiple sclerosis (MS) and stroke. However, therapeutic attempts to modulate
      neuroinflammation have proved difficult. Neuroinflammatory cells express HCA2, a
      receptor for the endogenous neuroprotective ketone body beta-hydroxybutyrate
      (BHB) as well as for the drugs dimethyl fumarate (DMF) and nicotinic acid, which
      have established efficacy in the treatment of MS and experimental stroke,
      respectively. This review summarizes the evidence that HCA2 is involved in the
      therapeutic effects of DMF, nicotinic acid, and ketone bodies in reducing
      neuroinflammation. Furthermore, we discuss the mechanisms underlying the
      beneficial effects of HCA2 activation in neuroinflammatory diseases and the
      therapeutic potential of recently developed synthetic ligands of HCA2. 

PMID- 25766752
TI  - N-Branched acyclic nucleoside phosphonates as monomers for the synthesis of
      modified oligonucleotides.
AB  - Protected N-branched nucleoside phosphonates containing adenine and thymine bases
      were prepared as the monomers for the introduction of aza-acyclic nucleotide
      units into modified oligonucleotides. The phosphotriester and phosphoramidite
      methods were used for the incorporation of modified and natural units,
      respectively. The solid phase synthesis of a series of nonamers containing one
      central modified unit was successfully performed in both 3'->5' and 5'->3'
      directions. Hybridization properties of the prepared oligoribonucleotides and
      oligodeoxyribonucleotides were evaluated. The measurement of thermal
      characteristics of the complexes of modified nonamers with the complementary
      strand revealed a considerable destabilizing effect of the introduced units. We
      also examined the substrate/inhibitory properties of aza-acyclic nucleoside
      phosphono-diphosphate derivatives (analogues of nucleoside triphosphates) but
      neither inhibition of human and bacterial DNA polymerases nor polymerase-mediated
      incorporation of these triphosphate analogues into short DNA was observed. 

PMID- 25766753
TI  - Relationship Between Psychosocial Burden of Skin Conditions and Symptoms:
      Measuring the Attributable Fraction.
AB  - Skin conditions often have a severe impact on the physical and psychosocial
      domains of patients' quality of life, but the relationship between these domains
      has been studied little. This study estimated the fraction of psychosocial burden
      that may be attributable to symptoms, using the Skindex-17 quality of life
      questionnaire (symptoms and psychosocial scales) in 2,487 outpatients. The excess
      proportion of psychosocial burden for each skin condition was computed. Overall,
      79.8% of the psychosocial burden of patients with severe symptoms may be
      attributable to the symptoms. For patients with mild symptoms this figure is
      49.7%. A great heterogeneity was observed, from -0.9% for patients with scars, up
      to more than 90% for conditions such as lichen planus and psoriasis. While these
      results will have to be confirmed in longitudinal studies, they seem to indicate
      that, by targeting specific symptoms, a substantial portion of the psychosocial
      burden of skin diseases could be spared. 

PMID- 25766754
TI  - The specificity of neural responses to music and their relation to voice
      processing: an fMRI-adaptation study.
AB  - Several studies have identified, using functional magnetic resonance imaging
      (fMRI), a region within the superior temporal gyrus that preferentially responds
      to musical stimuli. However, in most cases, significant responses to other
      complex stimuli, particularly human voice, were also observed. Thus, it remains
      unknown if the same neurons respond to both stimulus types, albeit with different
      strengths, or whether the responses observed with fMRI are generated by distinct,
      overlapping neural populations. To address this question, we conducted an fMRI
      experiment in which short music excerpts and human vocalizations were presented
      in a pseudo-random order. Critically, we performed an adaptation-based analysis
      in which responses to the stimuli were analyzed taking into account the category
      of the preceding stimulus. Our results confirm the presence of a region in the
      anterior STG that responds more strongly to music than voice. Moreover, we found
      a music-specific adaptation effect in this area, consistent with the existence of
      music-preferred neurons. Lack of differences between musicians and non-musicians
      argues against an expertise effect. These findings provide further support for
      neural separability between music and speech within the temporal lobe. 

PMID- 25766755
TI  - MPTP-induced parkinsonism in mice alters striatal and nigral xCT expression but
      is unaffected by the genetic loss of xCT.
AB  - Nigral cell loss in Parkinson's disease (PD) is associated with disturbed
      glutathione (GSH) and glutamate levels, leading to oxidative stress and
      excitotoxicity, respectively. System xc- is a plasma membrane antiporter that
      couples cystine import (amino acid that can be further used for the synthesis of
      GSH) with glutamate export to the extracellular environment, and can thus affect
      both oxidative stress and glutamate excitotoxicity. In the current study, we
      evaluated the involvement of system xc- in a progressive 1-methyl-4-phenyl
      1,2,3,6-tetrahydropyridine (MPTP) mouse model of PD. Our results indicate that
      the expression of xCT (the specific subunit of system xc-) undergoes region
      specific changes in MPTP-treated mice, with increased expression in the striatum,
      and decreased expression in the substantia nigra. Furthermore, mice lacking xCT
      were equally sensitive to the neurotoxic effects of MPTP compared to wild-type
      (WT) mice, as they demonstrate similar decreases in striatal dopamine content,
      striatal tyrosine hydroxylase (TH) expression, nigral TH immunopositive neurons
      and forelimb grip strength, five weeks after commencing MPTP treatment.
      Altogether, our data indicate that progressive lesioning with MPTP induces
      striatal and nigral dysregulation of system xc-. However, loss of system xc- does
      not affect MPTP-induced nigral dopaminergic neurodegeneration and motor
      impairment in mice.

PMID- 25766757
TI  - Electroencephalographic Finding in Idiopathic REM Sleep Behavior Disorder.
AB  - The REM sleep behavior disorder (RBD) is a type of parasomnia manifested by
      vivid, often frightening dreams associated with motor behaviors during REM sleep,
      sometimes causing injuries to patients themselves or to their bed partners. The
      polysomnographic features of RBD include increased muscle activity during REM
      sleep (REM sleep without atonia). The majority of RBD-affected persons are older
      men. The disorder might be idiopathic (iRBD) or secondary to neurological
      disorders of various kinds. iRBD management with pharmaceutical measures is
      usually straightforward and effective. Several longitudinal studies have revealed
      that a high proportion of iRBD patients convert to alpha-synucleinopathies such
      as Parkinson's disease and dementia with Lewy body disease (DLB). Considering
      this, many studies have been conducted to identify common clinical markers
      between alpha-synucleinopathies and iRBD or indicators for the future development
      of alpha-synucleinopathies in iRBD patients. In this context,
      electroencephalographic (EEG) slowing occurring while awake and asleep, which is
      frequently observed in DLB, has received much attention. Clarification of the
      association between EEG slowing and the presence of mild cognitive impairment,
      which is also commonly seen in early stages of DLB, has been particularly
      expected to offer a breakthrough for the identification of cases which might
      convert to alpha-synucleinopathies. In this article, we introduce the progress in
      quantitative EEG research in iRBD during the past decade. We also discuss the
      relationship between EEG findings and cognitive decline as well as the mechanisms
      of EEG changes or cognitive abnormalities in patients with the disorder. (c) 2015
      S. Karger AG, Basel.

PMID- 25766756
TI  - Altered serum glyceraldehyde-derived advanced glycation end product (AGE) and
      soluble AGE receptor levels indicate carbonyl stress in patients with
      schizophrenia.
AB  - Recent cross-sectional and longitudinal studies indicate that measurements of
      peripheral blood carbonyl stress markers such as the advanced glycation end
      product (AGE) pentosidine and the reactive carbonyl-detoxifying B6 vitamin
      pyridoxal could be used as therapeutic biological markers in subpopulations of
      schizophrenia patients. Glyceraldehyde-derived AGEs (Glycer-AGE) have strong
      neurotoxicity, and soluble receptors for AGEs (sRAGE) may ameliorate the effects
      of AGEs. In the present study, we measured Glycer-AGEs and sRAGE levels to
      determine their potential as diagnostic, therapeutic, or clinical biological
      markers in patients with schizophrenia. After enrollment of 61 admitted Japanese
      patients with acute schizophrenia and 39 healthy volunteers, 54 patients were
      followed up from the acute stage to remission. Serum biomarkers were measured in
      blood samples taken before breakfast using competitive enzyme-linked
      immunosorbent assays, and Glycer-AGEs were significantly higher and sRAGE levels
      were significantly lower in patients with acute schizophrenia than in healthy
      controls. Glycer-AGEs/sRAGE ratios were also higher in schizophrenia patients and
      were stable during the clinical course. Furthermore, discriminant analyses
      confirmed that Glycer-AGEs and Glycer-AGEs/sRAGE ratios are significant
      diagnostic markers for schizophrenia, and distinguished between patients and
      healthy controls in 70.0% of cases. However, these markers of carbonyl stress
      were not correlated with clinical features, including disease severity, or with
      daily chlorpromazine doses. These data indicate the potential of Glycer-AGEs,
      RAGEs, and their relative ratios as diagnostic markers for patients with
      schizophrenia. 

PMID- 25766758
TI  - Role of the luxS gene in initial biofilm formation by Streptococcus mutans.
AB  - Quorum sensing (QS) is a process by which bacteria communicate with each other by
      secreting chemical signals called autoinducers (AIs). Among Gram-negative and
      Gram-positive bacteria, AI-2 synthesized by the LuxS enzyme is widespread. The
      aim of this study was to evaluate the effect of QS luxS gene on initial biofilm
      formation by Streptococcus mutans. The bacterial cell surface properties,
      including cell hydrophobicity (bacterial adherence to hydrocarbons) and
      aggregation, which are important for initial adherence during biofilm
      development, were investigated. The biofilm adhesion assay was evaluated by the
      MTT method. The structures of the 5-hour biofilms were observed by using confocal
      laser scanning microscopy, and QS-related gene expressions were investigated by
      real-time PCR. The luxS mutant strain exhibited higher biofilm adherence and
      aggregation, but lower hydrophobicity than the wild-type strain. The confocal
      laser scanning microscopy images revealed that the wild-type strain tended to
      form smaller aggregates with uniform distribution, whereas the luxS mutant strain
      aggregated into distinct clusters easily discernible in the generated biofilm.
      Most of the genes examined were downregulated in the biofilms formed by the luxS
      mutant strain, except the gtfB gene. QS luxS gene can affect the initial biofilm
      formation by S. mutans.

PMID- 25766760
TI  - Squamous cell carcinoma of the scrotum: the revisit of a rare disease.

PMID- 25766759
TI  - Anti-phospholipase A2 receptor antibodies in recurrent membranous nephropathy.
AB  - About 70% of patients with primary membranous nephropathy (MN) have circulating
      anti-phospholipase A2 receptor (PLA2R) antibodies that correlate with disease
      activity, but their predictive value in post-transplant (Tx) recurrent MN is
      uncertain. We evaluated 26 patients, 18 with recurrent MN and 8 without
      recurrence, with serial post-Tx serum samples and renal biopsies to determine if
      patients with pre-Tx anti-PLA2R are at increased risk of recurrence as compared
      to seronegative patients and to determine if post-Tx changes in anti-PLA2R
      correspond to the clinical course. In the recurrent group, 10/17 patients had
      anti-PLA2R at the time of Tx versus 2/7 patients in the nonrecurrent group. The
      positive predictive value of pre-Tx anti-PLA2R for recurrence was 83%, while the
      negative predictive value was 42%. Persistence or reappearance of post-Tx anti
      PLA2R was associated with increasing proteinuria and resistant disease in 6/18
      cases; little or no proteinuria occurred in cases with pre-Tx anti-PLA2R and
      biopsy evidence of recurrence in which the antibodies resolved with standard
      immunosuppression. Some cases with positive pre-Tx anti-PLA2R were seronegative
      at the time of recurrence. In conclusion, patients with positive pre-Tx anti
      PLA2R should be monitored closely for recurrent MN. Persistence or reappearance
      of antibody post-Tx may indicate a more resistant disease.

PMID- 25766761
TI  - Interplay between the Virus and Host in Rift Valley Fever Pathogenesis.
AB  - Rift Valley fever virus (RVFV) belongs to the genus Phlebovirus, family
      Bunyaviridae, and carries single-stranded tripartite RNA segments. The virus is
      transmitted by mosquitoes and has caused large outbreaks among ruminants and
      humans in sub-Saharan African and Middle East countries. The disease is
      characterized by a sudden onset of fever, headache, muscle pain, joint pain,
      photophobia, and weakness. In most cases, patients recover from the disease after
      a period of weeks, but some also develop retinal or macular changes, which result
      in vision impairment that lasts for an undefined period of time, and severe
      disease, characterized by hemorrhagic fever or encephalitis. The virus also
      causes febrile illness resulting in a high rate of spontaneous abortions in
      ruminants. The handling of wild-type RVFV requires high-containment facilities,
      including biosafety level 4 or enhanced biosafety level 3 laboratories.
      Nonetheless, studies clarifying the mechanisms of the RVFV-induced diseases and
      preventing them are areas of active research throughout the world. By primarily
      referring to recent studies using several animal model systems, protein
      expression systems, and specific mutant viruses, this review describes the
      current knowledge about the mechanisms of pathogenesis of RVF and biological
      functions of various viral proteins that affect RVFV pathogenicity. 

PMID- 25766762
TI  - Dynamic designing of microstructures by chemical gradient-mediated growth.
AB  - Shape is one of the most important determinants of the properties of
      microstructures. Despite of a recent progress on microfabrication techniques,
      production of three-dimensional micro-objects are yet to be fully achieved.
      Nature uses reaction-diffusion process during bottom-up self-assembly to create
      functional shapes and patterns with high complexity. Here we report a method to
      produce polymeric microstructures by using a dynamic reaction-diffusion process
      during top-down photolithography, providing unprecedented control over shape and
      composition. In radical polymerization, oxygen inhibits reaction, and therefore
      diffusion of oxygen significantly alters spatial distribution of growth rate.
      Therefore, growth pathways of the microstructures can be controlled by
      engineering a concentration gradient of oxygen. Moreover, stepwise control of
      chemical gradients enables the creation of highly complex microstructures. The
      ease of use and high controllability of this technology provide new opportunities
      for microfabrication and for fundamental studies on the relationships between
      shape and function for the materials. 

PMID- 25766763
TI  - Imiquimod-induced AMPK activation causes translation attenuation and apoptosis
      but not autophagy.
AB  - BACKGROUND: AMP-activated protein kinase (AMPK), a principal intracellular energy
      sensor, plays a crucial role in cell growth, proliferation, apoptosis and
      autophagy. Imiquimod (IMQ) directly exhibits anti-tumor activity through the
      induction of apoptosis and autophagic cell death. OBJECTIVE: To evaluate the role
      of AMPK in IMQ-induced apoptosis and autophagy. METHODS: The phosphorylation of
      AMPK and its substrates was detected by immunoblotting. ATP contents were
      analyzed by an ATP bioluminescence assay. The upstream signaling for AMPK
      activation was dissected by examination of TLR7/8 expression, over-expression of
      TLR7/8, the addition of AMPK kinase inhibitors, and the genetic silencing of
      Myd88 and LKB1. The role of AMPK activation in IMQ-induced autophagy and
      apoptosis was assessed by inhibiting AMPK, genetically silencing AMPK and over
      expressing AMPK dominant-negative mutants. Autophagy and apoptosis were evaluated
      by a DNA content assay, immunoblotting, EGFP-LC3 puncta detection and acridine
      orange staining. RESULTS: IMQ could activate AMPK and autophagy in cancer cells
      not expressing TLR7/8. IMQ caused ATP depletion and induced LKB1-mediated AMPK
      activation. The down-regulation of AMPK activity via pharmacological inhibition
      and genetic silencing resulted in reduced IMQ-induced apoptosis but did not
      influence autophagy, and this rescue effect was associated with the retention of
      translation factor activity and anti-apoptotic Bcl-2 family member Mcl-1 protein
      expression levels. CONCLUSION: IMQ induces AMPK activation independent of TLR7/8
      expression, resulting in translation inhibition and subsequent apoptosis through
      ATP depletion and LKB1 signaling, in skin tumor cells.

PMID- 25766765
TI  - Possible involvement of CCR4+ CD8+ T cells and elevated plasma CCL22 and CCL17 in
      patients with rhododenol-induced leukoderma.

PMID- 25766764
TI  - Mutation study for 9 genes in 23 unrelated patients with autosomal recessive
      congenital ichthyosis in Japan and Malaysia.

PMID- 25766766
TI  - Hedgehog signaling in basal cell carcinoma.
AB  - Basal cell carcinoma (BCC), the most common type of skin cancer, is occasionally
      aggressive with deep invasion, destruction of adjacent structures, recurrence
      and, on very rare occasions, regional and distant metastases. Mutations that
      occur in BCC in hedgehog (Hh) pathway genes primarily involve the genes encoding
      patched homolog (PTCH) and smoothened homolog (SMO). Several animal models have
      demonstrated the functional relevance of genetic alterations in the Hh pathway
      during tumorigenesis. Recently, targeted therapy has become available both
      commercially and in the context of human clinical trials. Interestingly, Hh
      pathway inhibitors not only suppress BCC progression but also promote acquired
      immune responses. Since immune responses are crucial for long-term tumor control,
      new clinical trials, such as those involving a combination of Hh inhibitors with
      immune modifiers, are needed to supplement standard methods of tumor control. 

PMID- 25766767
TI  - Development and utility of the FDA 'GutProbe' DNA microarray for identification,
      genotyping and metagenomic analysis of commercially available probiotics.
AB  - AIM: Lactic acid bacteria are beneficial microbes added to many food products and
      dietary supplements for their purported health benefits. Proper identification of
      bacteria is important to assess safety as well as proper product labelling. A
      custom microarray (FDA GutProbe) was developed to verify accurate labelling in
      commercial dietary supplements. METHODS AND RESULTS: Strain-specific attribution
      was achieved with GutProbe array which contains genes from the most commonly
      found species in probiotic supplements and food ingredients. Applied utility of
      the array was assessed with direct from product DNA hybridization to determine
      (i) if identification of multiple strains in one sample can be conducted and (ii)
      if any lot-to-lot variations exist with eight probiotics found on the US market.
      CONCLUSIONS: GutProbe is a useful tool in identifying a mixture of microbials in
      probiotics and did reveal some product variations. In addition, the array is able
      to identify lot-to-lot differences in these products. These strain level
      attribution may be useful for routine monitoring of batch variation as part of a
      'Good Manufacturing Practices' process. SIGNIFICANCE AND IMPACT OF THE STUDY: The
      FDA GutProbe is an efficient and reliable platform to identify the presence of
      microbial ingredients and determining microbe differences in dietary supplements.
      The GutProbe is a fast, rapid method for direct community profiling or food
      matrix sampling.

PMID- 25766768
TI  - Copper(I)-catalyzed heteroannulation of [60]fullerene with ketoxime acetates:
      preparation of novel 1-fulleropyrrolines.
AB  - A cuprous bromide-catalyzed heteroannulation reaction of [60]fullerene with
      ketoxime acetates has been exploited to prepare novel 1-fulleropyrrolines through
      the cleavage of N-O and C-H bonds and formation of C-C and C-N bonds under
      thermal conditions. A plausible mechanism for the formation of 1
      fulleropyrrolines is proposed on the basis of the experimental results. The
      electrochemistry of the obtained products has also been investigated. 

PMID- 25766769
TI  - Detection of monoclonal integration of bovine leukemia virus proviral DNA as a
      malignant marker in two enzootic bovine leukosis cases with difficult clinical
      diagnosis.
AB  - Monoclonal integration of bovine leukemia virus (BLV) proviral DNA into bovine
      genomes was detected in peripheral blood from two clinical cases of enzootic
      bovine leukosis (EBL) without enlargement of superficial lymph nodes. A BLV
      specific probe hybridized with 1 to 3 EcoRI and HindIII fragments in these 2
      atypical EBL cattle by Southern blotting and hybridization, as well as in 3
      typical EBL cattle. The probe also hybridized to a large number of EcoRI and
      HindIII fragments in 5 cattle with persistent leukosis. These results suggest
      that the detection of monoclonal integration of BLV provirus into the host genome
      may serve as a marker of monoclonal proliferation and malignancy in difficult to
      diagnose EBL cattle. 

PMID- 25766770
TI  - Chordoma of the thoracic vertebrae in a Bengal tiger (Panthera tigris tigris).
AB  - A 19-year-old female Bengal tiger (Panthera tigris tigris) was presented with
      hind limb weakness, ataxia and respiratory distress. Computed tomography revealed
      a mass between the left side of the T7 vertebra and the base of the left 7th rib.
      The tiger then died, and necropsy was performed. Grossly, the vertebral mass was
      6 * 5.7 * 3 cm, and invaded the adjacent vertebral bone and compressed the T7
      spinal cord. Histologically, the mass was composed of large, clear, vacuolated
      and polygonal cells with osteochondral matrix. Cellular and nuclear atypia were
      moderate. The vacuolated cells stained positively for cytokeratin and vimentin
      and negatively for S-100. Based on these findings, the present case was diagnosed
      as a vertebral chordoma; the first report in a tiger. 

PMID- 25766771
TI  - Cytocompatibility of PLA/Nano-HA composites for interface fixation.
AB  - OBJECTIVE: When preliminary tests have confirmed a nano-hydroxyapatite (Nano-HA)
      content of 20% of the polylactic acid (PLA) composite material of Nano-HA
      interface fixation material for biomechanical requirements, there is a need for
      further observation of its biocompatibility and clinical applications, to provide
      reference data. METHODS: Preparation of Nano-HA content of 20% PLA composite Nano
      HA bone substitute material and extract. The establishment of the negative
      control group (containing 10% fetal bovine serum in DMEM complete medium),
      experimental group (extract), the positive control group (mass concentration of
      0.64% phenol), and a co-culture of rabbit bone marrow mesenchymal stem cells
      (rBMSC) and materials extraction liquid. Observation of the morphological changes
      in rBMSC in culture at time points of 3, 5, and 7 days, the use of the MTT assay,
      and determination of the relative growth in the above set of rBMSC in cell
      culture at 3, 5, and 7 days, to judge the material's cytotoxicity. RESULTS: With
      time, the absorbance value of the three groups of cells were significantly
      increased (P < 0.01). The relative growth of the rBMSCs in experimental group in
      the first 3, 5, and 7 days was 95.3%, 96.8% and 97.6%; the cytotoxicity was
      according to the national standards I; the difference was not significant (P >
      0.05) between the the experimental group and the negative control group; there
      was a significant difference between the positive control group and the other 2
      groups (P < 0.05). Cells in the experimental group were seen having normal
      morphology, and spindle-shaped adherent growth. CONCLUSION: PLA composite
      artificial bone materials and Nano-HA show good cell compatibility, and the
      values for cytotoxicity, with reference to GB/T16886.5.2003 (China) standards,
      are in the safe range.

PMID- 25766772
TI  - Age-related differences in electroencephalogram connectivity and network
      topology.
AB  - To better understand age-related differences in brain function and behavior,
      connectivity between brain regions was estimated from electroencephalogram source
      time series in eyes closed versus eyes open resting condition. In beta band,
      decrease of connectivity upon eyes opening was more pronounced in younger than in
      older participants. The extent of this decrease was associated with reaction time
      in attention tasks, and this relationship was fully mediated by participants'
      age, implying that physiological processes, which lead to age-related slowing,
      include changes in beta reactivity. Graph-theoretical analysis showed a decrease
      of modularity and clustering in beta and gamma band networks in older adults,
      implying that age makes brain networks more random. The overall number of nodes
      identified as hubs in posterior cortical regions decreased in older participants.
      At the same time, increase of connectedness of anterior nodes, probably
      reflecting compensatory activation of the anterior attentional system, was
      observed in beta-band network of older adults. These findings show that normal
      aging mostly affects interactions in beta band, which are probably involved in
      attentional processes. 

PMID- 25766773
TI  - Prevalence of hepatitis B and C infection and associated factors in people living
      with HIV in Midwestern Brazil.
AB  - This study aimed to estimate the prevalence of infection by the hepatitis B virus
      (HBV) and hepatitis C virus (HCV) in people infected by the human
      immunodeficiency virus (HIV) and analyze sociodemographic and behavioral factors
      associated with such co-infection. A cross-section study was performed in 495
      individuals treated at a public center in the city of Goiania. Participants were
      interviewed and blood collected for evaluation of serological and molecular
      markers for HBV and HCV. The rate of exposure to HBV was 33.5% (95% CI 29.4
      37.9). Nineteen patients (3.8%) were diagnosed as HBV carriers, of whom 68.4%
      were HBV DNA positive. The prevalence of anti-HCV was 9.7% (95% CI 7.3-12.7).
      Genotype 1a was identified in 72.7% of the PCR samples positive for HCV. Co
      infection by all three viruses was 4.4% (95% CI 2.9-6.8). Being, male, aged >=40
      years, history of sexually transmitted disease (STD), and having homosexual
      practices were independently associated with the presence of markers of HBV
      exposure. A history of injectable drugs use and STDs showed association with HCV
      seropositivity. Approximately 50% of participants were not aware of their HBV and
      HCV serostatus. The results obtained may contribute to assess the burden of viral
      hepatitis in people living with HIV and to guiding preventive measures for more
      vulnerable groups. 

PMID- 25766774
TI  - Ventricular arrhythmias from the coronary venous system: Prevalence, mapping, and
      ablation.
AB  - BACKGROUND: The coronary venous system (CVS) is linked to the origin of
      idiopathic epicardial ventricular arrhythmias (VAs). OBJECTIVE: The purpose of
      this study was to identify the prevalence and effective mapping/ablation
      strategies for idiopathic VAs mapped to the CVS. METHODS: Detailed activation and
      pace-mapping of the right ventricle (RV), left ventricle (LV), CVS, and aortic
      cusps was performed, followed by attempted catheter ablation. RESULTS: Forty
      seven of 511 patients with non-scar-related VAs (21 males, age 55 +/- 15) had
      earliest activation in the CVS, 39 +/- 18 ms before QRS. Twenty-five (53%) were
      in the great cardiac vein, 19 (40%) in the anterior interventricular vein, and 3
      (7%) in the middle cardiac vein. We ablated inside CVS in 32 patients (68%) at
      the earliest activation site, in 18 patients at an adjacent CVS site, and in 14
      patients because of an inability to advance the catheter in 4, inadequate power
      delivery in 2, and for safer distance from the coronary artery in 8. Proximity to
      coronaries precluded ablation inside the CVS in the remaining 15 patients (32%),
      who underwent ablation from adjacent left sinus of Valsalva, RV or LV
      endocardium, or LV epicardium. Success was achieved in 17 of 18 (94%) ablated at
      the earliest CVS site and in 16 of 29 (55%) ablated at adjacent CVS or non-CVS
      sites. CONCLUSION: Idiopathic VAs are occasionally (9%) linked to CVS. Although
      ablation at the earliest CVS site is effective, it is often (62%) precluded,
      mainly because of proximity to coronary arteries. Ablation at adjacent CVS and
      non-CVS sites can be successful in 55% of these anatomically challenging cases,
      for an overall ablation success rate of 70%.

PMID- 25766775
TI  - Ablation of atrial fibrillation and esophageal injury: Role of bipolar and
      unipolar energy using a novel multipolar irrigated ablation catheter.
AB  - BACKGROUND: The circular nMARQ ablation catheter is a useful tool for pulmonary
      vein isolation (PVI). Some studies reported a high incidence of esophageal
      lesions by using this catheter. OBJECTIVE: The primary aim of this study was to
      compare the effects on the esophageal wall of bipolar and unipolar energy applied
      by the nMARQ ablation catheter during AF ablation. METHODS: Forty patients (mean
      age 53 +/- 8 years; 26 [65%] men) were enrolled to perform PVI for symptomatic
      atrial fibrillation. Thirty patients underwent PVI with the nMARQ catheter (group
      1) and 10 patients with the ThermoCool Surround Flow catheter (group 2). The
      procedures were performed with the CARTO3 system. All patients received an
      esophageal temperature probe. In group 1, we delivered unipolar energy on the
      left posterior wall with power between 15 and 18 W or bipolar energy with power
      at 15 W. In group 2, unipolar energy was delivered on the posterior atrial wall
      at 20-25 W power. All patients underwent esophagoscopy the day after the
      procedure. RESULTS: No patients had procedural complications. In group 1, bipolar
      energy was associated with a lower esophageal temperature increase as compared
      with unipolar energy (0.6 degrees C [range 0-2.2 degrees C] vs 2.1 degrees C
      [range 0.8-2.9 degrees C]; P < .001). Unipolar energy was associated with a
      similar temperature increase in the 2 groups (1.9 degrees C [range 0.8-2.9
      degrees C] in group 1 vs 1.7 degrees C [range 0.7-2.9 degrees C] in group 2; P =
      .49). No patient had esophageal injury. CONCLUSION: The use of the nMARQ catheter
      for PVI is feasible and safe. The use of 15 W for bipolar energy or 15-18 W for
      unipolar energy is an optimal strategy to avoid esophageal injury with this new
      catheter.

PMID- 25766776
TI  - Accuracy of first-trimester ultrasound in diagnosis of tubal ectopic pregnancy in
      the absence of an obvious extrauterine embryo: systematic review and meta
      analysis.
AB  - OBJECTIVES: To determine the accuracy of ultrasound in the diagnosis of a tubal
      ectopic pregnancy in the absence of an obvious extrauterine embryo. METHODS: This
      was a systematic review conducted in accordance with the PRISMA statement and
      registered with PROSPERO. We searched MEDLINE, EMBASE and The Cochrane Library
      for relevant citations from database inception to July 2014. Studies were
      selected in a two-stage process and their data extracted by two reviewers.
      Accuracy measures were calculated for each ultrasound sign, i.e. empty uterus,
      pseudosac, adnexal mass and free fluid in the pouch of Douglas, alone and in
      various combinations. Individual study estimates were plotted in summary receiver
      operating characteristics curves and forest plots for examination of
      heterogeneity. The quality of included studies was assessed. RESULTS: Thirty-one
      studies including 5858 women were selected from 19,959 citations. Following meta
      analysis, an empty uterus on ultrasound was found to predict an ectopic pregnancy
      with a sensitivity of 81.1% (95% CI, 42.1-96.2%) and specificity of 79.5% (95%
      CI, 68.9-87.1%). The corresponding performance of the pseudosac, adnexal mass and
      free fluid were: 5.5% (95% CI, 3.3-9.0%) and 94.2% (95% CI, 75.9-98.8%); 63.5%
      (95% CI, 48.5-76.3%) and 91.4% (95% CI, 83.6-95.7%); and 47.2% (95% CI, 33.2
      61.7%) and 92.3% (95% CI, 85.6-96.0%), respectively. CONCLUSION: Visualization of
      an empty uterus, adnexal mass, free fluid or a pseudosac has poor sensitivity for
      the diagnosis of a tubal pregnancy when an obvious extrauterine embryo is absent,
      but it has good specificity. We can therefore infer that ultrasound is more
      useful for 'ruling in' a tubal pregnancy than 'ruling out' one. However, the
      findings were limited by the poor quality of some included studies and
      heterogeneity in the index test and reference standard.

PMID- 25766777
TI  - A murine monoclonal antibody to glycogen: characterization of epitope-fine
      specificity by saturation transfer difference (STD) NMR spectroscopy and its use
      in mycobacterial capsular alpha-glucan research.
AB  - Mycobacterium tuberculosis, the causative agent of tuberculosis (TB), is a major
      pathogen responsible for 1.5 million deaths annually. This bacterium is
      characterized by a highly unusual and impermeable cell envelope, which plays a
      key role in mycobacterial survival and virulence. Although many studies have
      focused on the composition and functioning of the mycobacterial cell envelope,
      the capsular alpha-glucan has received relatively minor attention. Here we show
      that a murine monoclonal antibody (Mab) directed against glycogen cross-reacts
      with mycobacterial alpha-glucans, polymers of alpha(1-4)-linked glucose residues
      with alpha(1-6)-branch points. We identified the Mab epitope specificity by
      saturation transfer difference NMR and show that the alpha(1-4)-linked glucose
      residues are important in glucan-Mab interaction. The minimal epitope is formed
      by (linear) maltotriose. Notably, a Mycobacterium mutant lacking the branching
      enzyme GlgB does not react with the Mab; this suggests that the alpha(1-6)
      branches form part of the epitope. These seemingly conflicting data can be
      explained by the fact that in the mutant the linear form of the alpha-glucan
      (amylose) is insoluble. This Mab was subsequently used to develop several
      techniques helpful in capsular alpha-glucan research. By using a capsular glucan
      screening methodology based on this Mab we were able to identify several unknown
      genes involved in capsular alpha-glucan biogenesis. Additionally, we developed
      two methods for the detection of capsular alpha-glucan levels. This study
      therefore opens new ways to study capsular alpha-glucan and to identify possible
      targets for further research. 

PMID- 25766778
TI  - FoxP3+ T regulatory cells and immunomodulation after Schistosoma mansoni egg
      antigen immunization in experimental model of inflammatory bowel disease.
AB  - To assess the effect of Schistosoma mansoni egg antigen immunization on the
      immunomodulation in dextran sodium sulfate (DSS) induced colitis as an
      experimental model of IBD in comparison to non immunization and healthy control.
      The study was performed on 180 mice; 25 healthy control, 15 to identify the
      inflammatory peak of DSS, 25 received DSS for 7 days; 90 infected with S. mansoni
      cercariae to collect eggs for antigen preparation, and 25 immunized with the
      prepared antigen then received DSS course. Disease activity index, macroscopic &
      microscopic inflammatory scores, FoxP3+ T regulatory cell count, myeloperoxidase
      activity, and Th1/Th2 cytokine profile were compared in studied groups.
      Immunization induced both FoxP3+ T(regs) and Th2 cytokines to establish a state
      of immune homeostasis and create a quiescent steadier immune response to DSS. S.
      mansoni egg antigen succeeded in acting like a prophylactic helminthic therapy as
      it has a profitable modulatory effect on DSS-induced colitis model.

PMID- 25766780
TI  - Comparing Mycobacterium tuberculosis genomes using genome topology networks.
AB  - BACKGROUND: Over the last decade, emerging research methods, such as comparative
      genomic analysis and phylogenetic study, have yielded new insights into genotypes
      and phenotypes of closely related bacterial strains. Several findings have
      revealed that genomic structural variations (SVs), including gene gain/loss, gene
      duplication and genome rearrangement, can lead to different phenotypes among
      strains, and an investigation of genes affected by SVs may extend our knowledge
      of the relationships between SVs and phenotypes in microbes, especially in
      pathogenic bacteria. RESULTS: In this work, we introduce a 'Genome Topology
      Network' (GTN) method based on gene homology and gene locations to analyze
      genomic SVs and perform phylogenetic analysis. Furthermore, the concept of
      'unfixed ortholog' has been proposed, whose members are affected by SVs in genome
      topology among close species. To improve the precision of 'unfixed ortholog'
      recognition, a strategy to detect annotation differences and complete gene
      annotation was applied. To assess the GTN method, a set of thirteen complete M.
      tuberculosis genomes was analyzed as a case study. GTNs with two different gene
      homology-assigning methods were built, the Clusters of Orthologous Groups (COG)
      method and the orthoMCL clustering method, and two phylogenetic trees were
      constructed accordingly, which may provide additional insights into whole genome
      based phylogenetic analysis. We obtained 24 unfixable COG groups, of which most
      members were related to immunogenicity and drug resistance, such as PPE-repeat
      proteins (COG5651) and transcriptional regulator TetR gene family members
      (COG1309). CONCLUSIONS: The GTN method has been implemented in PERL and released
      on our website. The tool can be downloaded from
      http://homepage.fudan.edu.cn/zhouyan/gtn/ , and allows re-annotating the 'lost'
      genes among closely related genomes, analyzing genes affected by SVs, and
      performing phylogenetic analysis. With this tool, many immunogenic-related and
      drug resistance-related genes were found to be affected by SVs in M. tuberculosis
      genomes. We believe that the GTN method will be suitable for the exploration of
      genomic SVs in connection with biological features of bacterial strains, and that
      GTN-based phylogenetic analysis will provide additional insights into whole
      genome-based phylogenetic analysis.

PMID- 25766781
TI  - Optimizing strontium ruthenate thin films for near-infrared plasmonic
      applications.
AB  - Several new plasmonic materials have recently been introduced in order to achieve
      better temperature stability than conventional plasmonic metals and control field
      localization with a choice of plasma frequencies in a wide spectral range. Here,
      epitaxial SrRuO3 thin films with low surface roughness fabricated by pulsed laser
      deposition are studied. The influence of the oxygen deposition pressure (20-300
      mTorr) on the charge carrier dynamics and optical constants of the thin films in
      the near-infrared spectral range is elucidated. It is demonstrated that SrRuO3
      thin films exhibit plasmonic behavior of the thin films in the near-infrared
      spectral range with the plasma frequency in 3.16-3.86 eV range and epsilon-near
      zero wavelength in 1.11-1.47 MUm range that could be controlled by the deposition
      conditions. The possible applications of these films range from the heat
      generating nanostructures in the near-infrared spectral range, to metamaterial
      based ideal absorbers and epsilon-near-zero components, where the interplay
      between real and imaginary parts of the permittivity in a given spectral range is
      needed for optimizing the spectral performance.

PMID- 25766782
TI  - Chemokine CXCL-1: activity in the vitreous during proliferative
      vitreoretinopathy.
AB  - The aim of this study was to investigate CXCL-1 chemokine levels in the vitreous
      during rhegmatogenous retinal detachment (RRD) with and without proliferative
      vitreoretinopathy (PVR) and identify possible correlations with clinical
      parameters (extent and duration or RRD and PVR grade). Vitreous samples from
      patients with primary RRD with or without PVR were collected and assayed using a
      double antibody enzyme-linked immunosorbent assay (ELISA). Eleven vitreous
      samples from organ donors were employed as a control group. CXCL-1 levels were
      measured in 35 vitreous samples from 35 RRD patients. Mean CXCL-1 levels (64.82
      +/- 6.47 pg/ml) were significantly higher (P = 0.048) compared to controls. There
      was a significant positive correlation between CXCL-1 levels and the extent of
      the detachment (r = 0.794, P = 0.006). Peak CXCL-1 levels coincided with 3+
      quadrant RRD, an interim of 29-60 days' duration and PVR grade B. Increased CXCL
      1 levels may be indicative of mild inflammation in the detached retina and the
      adjacent vitreous. The results of the present study may provide novel insight
      into the complex interactions taking place during the early and late stages of
      RRD complicated by PVR. 

PMID- 25766783
TI  - The Corynebacterium glutamicum mycothiol peroxidase is a reactive oxygen species
      scavenging enzyme that shows promiscuity in thiol redox control.
AB  - Cysteine glutathione peroxidases (CysGPxs) control oxidative stress levels by
      reducing hydroperoxides at the expense of cysteine thiol (-SH) oxidation, and the
      recovery of their peroxidatic activity is generally accomplished by thioredoxin
      (Trx). Corynebacterium glutamicum mycothiol peroxidase (Mpx) is a member of the
      CysGPx family. We discovered that its recycling is controlled by both the Trx and
      the mycothiol (MSH) pathway. After H2 O2 reduction, a sulfenic acid (-SOH) is
      formed on the peroxidatic cysteine (Cys36), which then reacts with the resolving
      cysteine (Cys79), forming an intramolecular disulfide (S-S), which is reduced by
      Trx. Alternatively, the sulfenic acid reacts with MSH and forms a mixed
      disulfide. Mycoredoxin 1 (Mrx1) reduces the mixed disulfide, in which Mrx1 acts
      in combination with MSH and mycothiol disulfide reductase as a biological
      relevant monothiol reducing system. Remarkably, Trx can also take over the role
      of Mrx1 and reduce the Mpx-MSH mixed disulfide using a dithiol mechanism.
      Furthermore, Mpx is important for cellular survival under H2 O2 stress, and its
      gene expression is clearly induced upon H2 O2 challenge. These findings add a new
      dimension to the redox control and the functioning of CysGPxs in general. 

PMID- 25766784
TI  - Physics for better human societies: reply to comments on "Statistical physics of
      crime: a review".

PMID- 25766785
TI  - Structural and electronic properties of organo-halide hybrid perovskites from ab
      initio molecular dynamics.
AB  - The last two years have seen the unprecedentedly rapid emergence of a new class
      of solar cells, based on hybrid organic-inorganic halide perovskites. The success
      of this class of materials is due to their outstanding photoelectrochemical
      properties coupled to their low cost, mainly solution-based, fabrication
      techniques. Solution processed materials are however often characterized by an
      inherent flexible structure, which is hardly mapped into a single local minimum
      energy structure. In this perspective, we report on the interplay between
      structural and electronic properties of hybrid lead iodide perovskites
      investigated using ab initio molecular dynamics (AIMD) simulations, which allow
      the dynamical simulation of disordered systems at finite temperature. We compare
      the prototypical MAPbI3 (MA = methylammonium) perovskite in its cubic and
      tetragonal structure with the trigonal phase of FAPbI3 (FA = formamidinium),
      investigating different starting arrangements of the organic cations. Despite the
      relatively short time scale amenable to AIMD, typically a few tens of ps, this
      analysis demonstrates the sizable structural flexibility of this class of
      materials, showing that the instantaneous structure could significantly differ
      from the time and thermal averaged structure. We also highlight the importance of
      the organic-inorganic interactions in determining the fluxional properties of
      this class of materials. A peculiar spatial localization of the valence and
      conduction band edges is also found, with a dynamics in the range of 0.1 ps,
      which is associated with the positional dynamics of the organic cations within
      the cubo-octahedral perovskite cage. This asymmetry in the spatial localization
      of the band edges is expected to ease exciton dissociation and assist the initial
      stages of charge separation, possibly constituting one of the key factors for the
      impressive photovoltaic performances of hybrid lead-iodide perovskites. 

PMID- 25766786
TI  - Bilateral minimal tension sacrospinous fixation in pelvic organ prolapse: an
      observational study.
AB  - OBJECTIVE: To evaluate the safety and the subjective and objective outcomes of
      bilateral minimal tension sacrospinous fixation for pelvic organ prolapse. STUDY
      DESIGN: This was a single-centre observational study conducted at the University
      Hospital, Urogynaecological Unit, with a certified urogynaecological surgeon. A
      cohort of 110 patients receiving modified bilateral sacrospinous fixation
      following a diagnosis of grade II-IV pelvic organ prolapse and defects of three
      pelvic compartments. Non-absorbable sutures were placed on each side of the
      sacrospinous ligament. The main aim was to achieve a minimal tension situation by
      intentionally leaving suture bridges on both sides of the suspension. The post
      surgical follow-up period was 14+/-7 months. The three characteristics of cure in
      functional surgery - anatomy, function, and subjective patient's judgement - were
      evaluated in this study. Primary outcomes were anatomic, functional, and
      subjective cures, that were measured pre- and postoperatively using the POP-Q
      system values, a validated pelvic quality-of-life questionnaire (P-QoL/D), and
      interviews regarding expectations, goal-setting, goal achievement, and
      satisfaction. Secondary outcome measures included data on surgical complications.
      Data analysis was performed with descriptive statistics, Wilcoxon tests, and Mann
      Whitney U-tests. RESULTS: A total of 110 patients underwent anterior and
      posterior colporrhaphy and minimal tension bilateral sacrospinous fixation. An
      objective anatomic cure was reported for 94.5% of patients, and significant
      improvement of all prolapse symptoms was observed following surgery (p<0.001).
      Full or partial fulfilment of the criteria for a subjective cure was demonstrated
      in 96% of the patients. Only 5.5% of the patients experienced postoperative
      urinary tract infections. No other complications requiring medical or surgical
      interventions were reported. CONCLUSION: Bilateral minimal tension sacrospinous
      fixation was associated with low morbidity, as well as excellent anatomic,
      functional, and subjective results at follow-up.

PMID- 25766787
TI  - Delivery rates after elective single cryopreserved embryo transfer related to
      embryo survival.
AB  - OBJECTIVE: The objective of this study was to assess if eSCET (elective Single
      Cryopreserved Embryo Transfer) outcome is related to blastomere survival rate.
      The final objective was to avoid multiple pregnancies and offer the best chances
      to women to achieve pregnancy even during their frozen-thawed embryo transfer
      (FET) cycles. STUDY DESIGN: Patients were included in this prospective
      observational study if they met the following criteria: (i) women age <37 years
      old; (ii) IVF of ICSI cycle rank <=2, (iii) eSET proposed during fresh embryo
      transfer cycle and (iv) >=1 good quality cryopreserved embryos available (<20%
      fragmentation and 4-5 blastomeres at day-2 or 7-9 blastomeres at day-3). Live
      birth rates (LBR) were compared into eSCET groups according to embryo survival
      (partially damaged or intact transferred embryo). RESULTS: We observed among
      selected patients, that partial loss of blastomeres (1 blastomere for day-2
      embryos, 1 or 2 blastomeres for day-3 embryos) following FET cycles did not
      affect LBR compared with intact embryo. CONCLUSION: These results underline the
      relevance of eSCET as a strategy to reduce multiple pregnancies frequency without
      reducing LBR.

PMID- 25766788
TI  - Covalent coupling of gum arabic onto superparamagnetic iron oxide nanoparticles
      for MRI cell labeling: physicochemical and in vitro characterization.
AB  - Gum arabic (GA) is a hydrophilic composite polysaccharide derived from exudates
      of Acacia senegal and Acacia seyal trees. It is biocompatible, possesses
      emulsifying and stabilizing properties and has been explored as coating agent of
      nanomaterials for biomedical applications, namely magnetic nanoparticles (MNPs).
      Previous studies focused on the adsorption of GA onto MNPs produced by co
      precipitation methods. In this work, MNPs produced by a thermal decomposition
      method, known to produce uniform particles with better crystalline properties,
      were used for the covalent coupling of GA through its free amine groups, which
      increases the stability of the coating layer. The MNPs were produced by thermal
      decomposition of Fe(acac)3 in organic solvent and, after ligand-exchange with
      meso-2,3-dimercaptosuccinic acid (DMSA), GA coating was achieved by the
      establishment of a covalent bond between DMSA and GA moieties. Clusters of
      several magnetic cores entrapped in a shell of GA were obtained, with good
      colloidal stability and promising magnetic relaxation properties (r2 /r1 ratio of
      350). HCT116 colorectal carcinoma cell line was used for in vitro cytotoxicity
      evaluation and cell-labeling efficiency studies. We show that, upon
      administration at the respective IC50 , GA coating enhances MNP cellular uptake
      by 19 times compared to particles bearing only DMSA moieties. Accordingly, in
      vitro MR images of cells incubated with increasing concentrations of GA-coated
      MNP present dose-dependent contrast enhancement. The obtained results suggest
      that the GA magnetic nanosystem could be used as a MRI contrast agent for cell
      labeling applications.

PMID- 25766790
TI  - Development of a genome copy specific RT-qPCR assay for divergent strains of type
      2 porcine reproductive and respiratory syndrome virus.
AB  - Porcine reproductive and respiratory syndrome virus (PRRSV) became a significant
      pathogen of swine upon its emergence in the late 1980s and since then has
      exemplified a rapidly evolving, constantly re-emerging pathogen. In addition to
      the challenges faced in development of vaccines and diagnostics, research on the
      basic molecular pathogenesis of PRRSV is also restrained by the ability to
      accurately and comparatively quantitate levels of replication in different
      tissues and between strains. This is further complicated by the presence of non
      genomic RNA within infected tissues which are generally detected with equivalent
      efficiency by RT-qPCR based techniques, thereby introducing inherent error in
      these measurements that may differ significantly by tissue and strain. To address
      this, an RT-qPCR based technique was developed which targets the viral RNA
      dependent RNA polymerase gene (nsp9) which is unique to genomic RNA, being absent
      from all subgenomic and heteroclite RNAs. This assay targets a region of
      considerable sequence conservation, and based on sequence only, should be
      quantitative for approximately 40% of all Type 2 PRRSV strains in GenBank for
      which nsp9 sequence is available. The assay was demonstrated to be linear over
      nine orders of magnitude (10(10)-10(2) copies) and can be readily adapted for
      multiplex detection of additional divergent PRRSV strains. This assay will add
      significantly to the ability to assess and compare PRRSV replication in a variety
      of tissues and between divergent strains, including highly pathogenic strains of
      considerable concern to the global pork industry. 

PMID- 25766789
TI  - Transcriptional regulation of N-acetylaspartate metabolism in the 5xFAD model of
      Alzheimer's disease: evidence for neuron-glia communication during energetic
      crisis.
AB  - N-acetylaspartate (NAA) provides a non-invasive clinical index of neuronal
      metabolic integrity across the entire neurodegenerative spectrum. While NAA
      function is not comprehensively defined, reductions in the brain are associated
      with compromised mitochondrial metabolism and are tightly linked to ATP. We have
      undertaken an analysis of abnormalities in NAA during early stage pathology in
      the 5xFAD mouse model of familial Alzheimer's disease and show here that
      dysregulated expression of the gene encoding for the rate-limiting NAA synthetic
      enzyme (Nat8L) is associated with deficits in mitochondrial oxidative
      phosphorylation in this model system. Downreguation of Nat8L is particularly
      pronounced in the 5xFAD hippocampus, and is preceded by a significant
      upregulation of oligodendrocytic aspartoacylase (aspa), which encodes for the
      sole known NAA-catabolizing enzyme in the brain. Reductions in 5xFAD NAA and
      Nat8L cannot be accounted for by discrepancies in either neuron content or
      activity of the substrate-providing malate-aspartate shuttle, thereby implicating
      transcriptional regulation in a coordinated response to pathological energetic
      crisis. A central role for ASPA in this response is supported by a parallel
      developmental analysis showing highly significant increases in Nat8L expression
      in an ASPA-null mouse model during a period of early postnatal development
      normally punctuated by the transcriptional upregulation of aspa. These results
      provide preliminary evidence of a signaling mechanism in Alzheimer's disease that
      involves cross talk between neurons and oligodendrocytes, and suggest that ASPA
      acts to negatively regulate Nat8L expression. This mechanism is proposed to be a
      fundamental means by which the brain conserves available substrate during energy
      crises. 

PMID- 25766791
TI  - Effects of beta2 agonists on post-thoracotomy pain incidence.
AB  - BACKGROUND: Pre-clinical research has shown beta2 -adrenoceptors to be essential
      for the antiallodynic action of antidepressant drugs in murine models of
      neuropathic pain and that sustained treatment with beta2 -agonists has an
      antiallodynic action. Here, we clinically investigated whether chronic beta2 
      agonist treatments may influence the incidence of post-thoracotomy chronic pain,
      defined as pain that recurs or persists along a thoracotomy scar more than 2
      months after surgery, either neuropathic or non-neuropathic. METHODS: We
      conducted an epidemiological study on patients operated by thoracotomy.
      Demographic data, medical history and treatments concomitant to the surgery were
      recorded at a follow-up visit. Information on perioperative treatments was
      collected from the anaesthesia records and confirmed by the patients. In patients
      with pain at the surgery level, post-thoracotomy chronic pain was assessed by
      clinical examination and numeric scale. Physical examination and DN4
      questionnaire were used to discriminate neuropathic and non-neuropathic chronic
      pain at scar level. RESULTS: One hundred and eighty-nine patients were included.
      Eighty-one patients reported persisting thoracic pain, with neuropathic
      characteristics in 58 of them (30% of the 189 patients). The most common chronic
      drugs during the perioperative period were inhaled beta2 -agonists (28.6%). The
      chronic use of beta2 -agonists was an independent predictor of thoracic
      neuropathic pain (but not of non-neuropathic pain) and was associated with a five
      fold decrease in the relative incidence of neuropathic pain [OR = 0.19 (0.06
      0.45)]. CONCLUSIONS: These data suggest a possible influence of chronic beta2 
      agonist treatments on neuropathic pain secondary to thoracotomy. This apparent
      preventive effect of beta2 -agonist treatments should warrant controlled clinical
      trials.

PMID- 25766792
TI  - Genotypic variability and antifungal susceptibility of Candida tropicalis
      isolated from patients with candiduria.
AB  - BACKGROUND: Candida tropicalis is an emerging major human pathogen in nosocomial
      infections, and it is considered the second or third species of Candida most
      isolated from urine cultures. AIMS: The study aimed at characterizing
      genotypically C. tropicalis strains from patients with candiduria in a university
      hospital, and assessed the antifungal susceptibility profile. METHODS: The study
      was conducted with hospitalized patients who developed urinary tract infection
      from C. tropicalis from June 2010 to June 2011 at the Grande Dourados University
      Hospital of the Federal University, Dourados, MS, Brazil. Susceptibility to the
      antifungal agents amphotericin B and fluconazole was determined by broth
      microdilution. The genotypic variability of isolates of C. tropicalis was
      analyzed by microsatellite markers and RAPD-PCR. RESULTS: Only one isolate was
      resistant to amphotericin B (MIC->16MUg/ml); the others were susceptible to
      fluconazole and amphotericin B. The genotypic variability by RAPD-PCR resulted in
      distinct profiles for RAPD markers. A total of 10 alleles were observed for the
      microsatellite loci, URA3 and CT14, which were grouped differently, and four
      associations were observed for locus URA3 and eight for locus CT14. CONCLUSIONS:
      C. tropicalis isolates from urine were susceptible to the antifungal agents
      tested. The genotyping techniques make possible proving the similarity and
      genetic diversity among isolates of C. tropicalis involved in nosocomial
      infections. This knowledge is important for the control and prevention of
      nosocomial infections caused by this yeast species.

PMID- 25766793
TI  - Nematophagous fungi from decomposing cattle faeces in Argentina.
AB  - BACKGROUND: Biological control of gastrointestinal nematodes of ruminants by use
      of nematophagous fungi would become part of any livestock parasite integral
      control system. Identifying autochthonous species that could then be selected for
      mass production is an important phase in the practical use of biological control.
      AIMS: To search for nematophagous fungi with potential use as biological control
      agents against gastrointestinal nematodes in Argentina. METHODS: Decomposing
      cattle faeces sampled in different locations were incubated in water agar 2% with
      Panagrellus sp. The developed nematophagous fungi were transferred to new water
      agar 2% plates and then to corn meal agar plates in order to carry out their
      identification. Fungal diversity and richness were also assessed. RESULTS:
      Seventeen species from nine genera of nematophagous fungi were found. Twelve
      species were nematode-trapping fungi and three species plus two fungi identified
      to genus level corresponded to endoparasitic fungi. Arthrobotrys conoides,
      Arthrobotrys oligospora, Duddingtonia flagrans, Monacrosporium doedycoides,
      Arthrobotrys robusta and Drechmeria coniospora were the most frequently isolated
      species overall in the whole study (6.6%, 5.7%, 5.7%, 5.7%, 4.7% and 4.7%,
      respectively) although other species were more frequently recorded at local
      levels such as Arthrobotrys pyriformis (18.8%). Only A. conoides has been
      previously isolated from ruminant faecal samples in Argentina. Five nematode
      trapping fungal species are mentioned for the first time in the Americas
      CONCLUSIONS: D. flagrans and A. conoides, both identified in the present study,
      are among the most promising ones as biological control agents against
      gastrointestinal nematodes of ruminants.

PMID- 25766794
TI  - Oxidative stress-mediated antiproliferative effects of furan-containing sulfur
      flavors in human leukemia Jurkat cells.
AB  - Antiproliferative effects of 15 sulfides were investigated in human leukemia
      Jurkat cells. Treatment with 5-50 MUM of nine monosulfides and two linear
      disulfides did not induce DNA fragmentation. Whereas, furan-containing sulfur
      flavors including methyl 2-methyl-3-furyl disulfide (MMFDS), bis (2-methyl-3
      furyl) disulfide (BMFDS), methyl furfuryl disulfide (MFDS) and difurfuryl
      disulfide (DFDS) induced DNA fragmentation to a varying extent in Jurkat cells.
      The cell viability-reduction effect of these sulfur flavors was in the following
      order: DFDS>BMFDS>MMFDS>>MFDS based on the IC50 values. MMFDS and BMFDS, but not
      DFDS, significantly increased the intracellular ROS level by 1.90- and 3.02-fold,
      respectively. Addition of N-acetylcysteine (NAC) or glutathione (GSH) partially
      suppressed induction of DNA fragmentation, apoptosis and caspase-3 activation by
      MMFDS and BMFDS. These results suggest that the furan-containing disulfides have
      a strong antiproliferative effect, and the oxidative stress and subsequent
      caspase-3 activation are involved in antiproliferative effect induced by MMFDS
      and BMFDS in Jurkat cells.

PMID- 25766795
TI  - Development of a multiplex PCR-ELISA method for the genetic authentication of
      Thunnus species and Katsuwonus pelamis in food products.
AB  - In the present work a PCR-ELISA technique for the authentication of Thunnus
      species was developed. This method is composed by four systems that can be used
      in a hierarchical way allowing the identification of several scombroids species;
      or each individual system independently. The hierarchical strategy, proposes a
      first step, to assign one sample to the Thunnus genus. Next, if the result is
      positive, several tests can be applied to assign the sample to some particular
      species of the Thunnus genus. In the case that the result is negative (absence of
      Thunnus species), it is possible to verify if Katsuwonus pelamis is included in
      the sample. The method even allows the detection of mixtures of these species in
      relatively low amounts (up to 1%). Finally, this method was applied to 11
      commercial samples to verify the labelling status of tuna products in the market,
      detecting that 18% were mislabelling. 

PMID- 25766796
TI  - Volatile profile of breast milk subjected to high-pressure processing or thermal
      treatment.
AB  - The effect of Holder pasteurisation (HoP) (62.5 degrees C for 30 min) or high
      pressure treatments (400 or 600 MPa for 3 or 6 min) on the volatile compound
      profile of human breast milk was evaluated, in order to compare both preservation
      technologies. A total of 46 different volatile compounds was found in milk
      samples. The most abundant compounds detected were aliphatic hydrocarbons. In
      general, the effect of some high-pressure treatments on the volatile profile of
      human milk was less intense than that caused by HoP. The treatments at 400 and
      600 MPa for 3 min maintained the volatile compounds at similar levels to those
      found in control milk samples. However, the application of 600 MPa for 6 min
      changed the original volatile compounds of human milk, even more than HoP. Since,
      HPP at 400 or 600 MPa for 3 min preserved the original volatile compounds of
      human milk, this novel process may be an alternative to thermal pasteurisation.

PMID- 25766797
TI  - Phenolic compounds and antioxidant activity of red wine made from grapes treated
      with different fungicides.
AB  - The effect of treating grapes with six fungicides, applied under critical
      agricultural practices (CAP) on levels of phenolic compounds and antioxidant
      activity of red wines of Monastrell variety was studied. Vinifications were
      performed through addition of active dry yeast (ADY). Measurement of phenolic
      compounds was made with HPLC-DAD. Determination of antioxidant activity was
      through reaction of the wine sample with the DPPH radical. The wine prepared from
      grapes treated with quinoxyfen shows a greater increase of phenolic compounds
      than the control wine. In contrast, the wine obtained from grapes treated with
      trifloxystrobin showed lower total concentration of phenolic compounds, including
      stilbenes, whilst treatments with kresoxim-methyl, fluquinconazole, and
      famoxadone slightly reduced their content. Hence, the use of these last four
      fungicides could cause a decrease in possible health benefits to consumers.
      Antioxidant activity hardly varied in the assays with quinoxyfen, fluquinconazole
      and famoxadone, and decreased in the other wines. 

PMID- 25766798
TI  - Development of a simple, sensitive and inexpensive ion-pairing cloud point
      extraction approach for the determination of trace inorganic arsenic species in
      spring water, beverage and rice samples by UV-Vis spectrophotometry.
AB  - The determination of inorganic arsenic species in water, beverages and foods
      become crucial in recent years, because arsenic species are considered
      carcinogenic and found at high concentrations in the samples. This communication
      describes a new cloud-point extraction (CPE) method for the determination of low
      quantity of arsenic species in the samples, purchased from the local market by UV
      Visible Spectrophotometer (UV-Vis). The method is based on selective ternary
      complex of As(V) with acridine orange (AOH(+)) being a versatile fluorescence
      cationic dye in presence of tartaric acid and polyethylene glycol tert
      octylphenyl ether (Triton X-114) at pH 5.0. Under the optimized conditions, a
      preconcentration factor of 65 and detection limit (3S blank/m) of 1.14 MUg L(-1)
      was obtained from the calibration curve constructed in the range of 4-450 MUg L(
      1) with a correlation coefficient of 0.9932 for As(V). The method is validated by
      the analysis of certified reference materials (CRMs).

PMID- 25766799
TI  - Textural and rheological properties of Pacific whiting surimi as affected by nano
      scaled fish bone and heating rates.
AB  - Textural and rheological properties of Pacific whiting (PW) surimi were
      investigated at various heating rates with the use of nano-scaled fish bone (NFB)
      and calcium chloride. Addition of NFB and slow heating improved gel strength
      significantly. Activity of endogenous transglutaminase (ETGase) from PW surimi
      was markedly induced by both NFB calcium and calcium chloride, showing an optimal
      temperature at 30 degrees C. Initial storage modulus increased as NFB calcium
      concentration increased and the same trend was maintained throughout the
      temperature sweep. Rheograms with temperature sweep at slow heating rate (1
      degrees C/min) exhibited two peaks at ~ 35 degrees C and ~ 70 degrees C. However,
      no peak was observed during temperature sweep from 20 to 90 degrees C at fast
      heating rate (20 degrees C/min). Protein patterns of surimi gels were affected by
      both heating rate and NFB calcium concentration. Under slow heating, myosin heavy
      chain intensity decreased with NFB calcium concentration, indicating formation of
      epsilon-(gamma-glutamyl) lysine cross-links by ETGase and NFB calcium ion.

PMID- 25766800
TI  - Absorption mechanism of whey-protein-delivered curcumin using Caco-2 cell
      monolayers.
AB  - Curcumin (CCM) is a bioactive polyphenolic compound that suffers a low
      bioavailability because of its low water solubility. In this work beta
      lactoglobulin (beta-Lg) and nanoemulsion were used as carriers to deliver
      curcumin. The pH stability of beta-Lg-CCM was investigated. The digestion of beta
      Lg-CCM and the nanoemulsion was studied using an in vitro gastrointestinal model.
      The effect of different carriers on the permeability of curcumin was assessed
      using the Caco-2 cell monolayer model. The results revealed that the water
      solubility and the pH stability of curcumin significantly increased by binding
      with beta-Lg. In SDS-PAGE experiments the beta-Lg-CCM complex and nanoemulsion
      were found to be resistant to pepsin digestion but sensitive to trypsin. In the
      permeability experiment it was shown that the digested nanoemulsion and beta-Lg
      CCM improved significantly the permeation rate of curcumin. 

PMID- 25766801
TI  - Phenylalanine and urea foliar applications to grapevine: effect on wine phenolic
      content.
AB  - Phenolic compounds play a key role in the organoleptic properties of wines.
      Viticultural practices may influence grape and wine phenolic content, thus
      determining their quality. The objective of this study was to evaluate the effect
      of foliar applications of phenylalanine and urea, at two different doses, on wine
      phenolic composition. Grapes were harvested at their optimal technological
      maturity and their respective wines were elaborated at small scale. Wine detailed
      phenolic composition was determined. Results revealed that the content of several
      anthocyanins and flavonols was enhanced by the application of both phenylalanine
      doses and by the application of the low dose of urea. In contrast, flavanols and
      non-flavonoid compounds were less affected by the foliar treatments. The findings
      seem to be related to the time of application, since anthocyanins and flavonols
      are accumulated after veraison. In conclusion, nitrogen foliar fertilization
      increased the phenolic content of Tempranillo wines. This could be of interest
      since anthocyanins and flavonols are associated with wine quality, especially
      with its color. 

PMID- 25766802
TI  - Production and characterization of functional biscuits obtained from purple
      wheat.
AB  - Purple wheat contains higher levels of anthocyanins than conventional wheat
      cultivars. The aim of this work was to produce anthocyanin-rich biscuits from
      purple wheat, and to characterize the final product. Control biscuits, having the
      same formulation but obtained from a non-pigmented wheat cultivar, were used for
      comparisons. Purple biscuits showed a level of total anthocyanins of 13.86 mg/kg
      cyanidin 3-O-glucoside and exhibited higher antioxidant activity than control.
      The volatile compounds profile of purple biscuits showed lower levels of lipid
      derived carboxylic acids and higher levels of alcohols and aldehydes than control
      biscuits, indicating a lower oxidative degradation of the lipid fraction. In
      particular, the ratio (lipid-derived alcohols+aldehydes)/acids accounted for 5.9
      in purple and 3.0 in control biscuits. The sensory score for friability and the
      spread ratio of purple biscuits accounted for 2.6 and 6.0, respectively.

PMID- 25766803
TI  - Structure and rheological characteristics of fucoidan from sea cucumber
      Apostichopus japonicus.
AB  - Sea cucumber is a traditional health food consumed in East Asia. In this study,
      fucoidan from sea cucumber Apostichopus japonicus (Aj-FUC) was isolated, and its
      structure and rheological characteristics were elucidated for the first time. Aj
      FUC was a branched polysaccharide mainly composed of a novel repeating unit
      [alpha-L-Fucp2(OSO3(-))-1 -> 3,(alpha-L-Fucp-1 -> 4-alpha-L-Fucp-1 ->)4-alpha-L
      Fucp2(OSO3(-))-1 -> 3-alpha-L-Fucp2(OSO3(-))], clarified by using a combination
      of infrared spectroscopy, methylation analysis, enzymatic degradation and nuclear
      magnetic resonance. In steady shear measurement, Aj-FUC manifested a non
      Newtonian shear-thinning behaviour at low shear rate (1-100 S(-1)) while
      exhibiting a non-Newtonian shear-thickening behaviour at high shear rate (100
      1000 S(-1)); salts had limited impact on its flow curve. Comparative study on
      viscosity and rheological behaviour of Aj-FUC and a linear fucoidan extracted
      from sea cucumber Acaudina molpadioides suggested that the presence of branch
      structure might significantly influence the rheological characteristics of
      fucoidan.

PMID- 25766804
TI  - Influence of roasting conditions on health-related compounds in different nuts.
AB  - Due to their health-beneficial ingredients the consumption of nuts can contribute
      to a healthy diet. The composition of hazelnuts, almonds, macadamia nuts,
      pistachios and walnuts regarding health-promoting and potentially harmful
      compounds was examined before and after roasting under different time and
      temperature conditions. Fatty acid compositions were not affected by roasting.
      Malondialdehyde increased with higher roasting temperatures (17-fold in walnuts).
      Levels of tocopherol isomers were reduced after roasting (alpha-T: 38%, beta-T:
      40%, gamma-T: 70%) and hydrophilic antioxidant capacity decreased significantly
      in hazelnuts (1.4-fold), macadamia nuts (1.7-fold) and walnuts (3.7-fold).
      Increasing roasting temperatures supported the formation of significant amounts
      of acrylamide only in almonds (1220 MUg kg(-1)). In general, nuts roasted at
      low/middle temperatures (120-160 degrees C) exhibited best sensory properties.
      Therefore, desired sensory quality along with a favourable healthy nut
      composition may be achieved by roasting over a low to medium temperature range.

PMID- 25766805
TI  - Polyphenols in whole rice grain: genetic diversity and health benefits.
AB  - Polyphenols, such as phenolic acid, anthocyanin and proanthocyanidins, have both
      nutraceutical properties and functional significance for human health.
      Identification of polyphenolic compounds and investigation of their genetic basis
      among diverse rice genotypes provides the basis for the improvement of the
      nutraceutical properties of whole rice grain. This review focuses on current
      information on the identification, genetic diversity, formation and distribution
      patterns of the phenolic acid, anthocyanin, and proanthocyanidins in whole rice
      grain. The genetic analysis of polyphenol content and antioxidant capacity allows
      the identification of several candidate genes or quantitative trait loci (QTL)
      responsible for polyphenol variation, which may be useful in improvement of these
      phytochemicals by breeding. Future challenges such as how to mitigate the effects
      of climate change while improving nutraceutical properties in whole grain, and
      how to use new technology to develop new rice high in nutraceutical properties
      are also presented. 

PMID- 25766806
TI  - Characterization of natural low-methoxyl pectin from sunflower head extracted by
      sodium citrate and purified by ultrafiltration.
AB  - Sunflower head pectin was extracted by 0.6% (w/v) sodium citrate under 85 degrees
      C, 3.5h with a solid to liquid ratio of 1:40, giving the maximum uronic acid
      yield of 16.90% (w/w). The extract was purified by an ultrafiltration membrane
      with the molecular weight cut-off of 8000 Da and dried by spray-drying to obtain
      SFHP(A) powders with particle diameters of 2-5 MUm. In comparison to the SFHP(B)
      extracted by ammonium oxalate and isolated by alcohol, SFHP(A) had a close DM
      (22.56%) but a considerably lower DAm (3.42%). HPSEC-MALLS analysis suggested
      that SFHP(A) has undergo a deeper degradation resulting in smaller Mw and Mn.
      HPAEC-PAD showed that SFHP(A) contains more neutral sugars since the degraded RG
      fragments have been retained during ultrafiltration. Finally, pectin aggregation
      in aqueous was investigated by FEG-SEM, which reveals that pectin network
      structure is constructed by microfilaments via coiling, intertwining and
      crosslinking.

PMID- 25766807
TI  - Blasting extrusion processing: the increase of soluble dietary fiber content and
      extraction of soluble-fiber polysaccharides from wheat bran.
AB  - In this study, soluble dietary fiber (SDF) content of wheat bran was
      significantly increased from 9.82 +/- 0.16 (w/w, %) to 16.72 +/- 0.28 (w/w, %) by
      a novel blasting extrusion processing with enhanced water retention capacity and
      the swelling capacity. In addition, a water-soluble polysaccharide (WBP) was
      isolated and extracted from extruded SDF. WBP was successfully purified from SDF
      by column chromatography systems with the average molecular weight (Mw) of 4.7 *
      10(4)Da, containing arabinose, xylose, glucose, and galactose. With the molar
      ratio of 0.76:0.99:1.00:0.12. Our results suggest that WBP owned 1 -> 2, 1 -> 3,
      1 -> 2, 6 and 1 -> 4, 1 -> 4, 6 glycosidic bonds in the absence of 1 ->, 1 -> 6
      glycosidic bonds. In vitro antioxidant assays (DPPH, ABTS+ radical scavenging
      capacities, and ferric ion reducing capacity) demonstrated that WBP possesses
      good antioxidant capacity, and it could be potentially used as a natural
      antioxidant for use in functional food, cosmetic and pharmaceutical industries.

PMID- 25766808
TI  - Sorghum flour fractions: correlations among polysaccharides, phenolic compounds,
      antioxidant activity and glycemic index.
AB  - Nutrients composition, phenolic compounds, antioxidant activity and estimated
      glycemic index (EGI) were evaluated in sorghum bran (SB) and decorticated sorghum
      flour (DSF), obtained by a rice-polisher, as well as whole sorghum flour (WSF).
      Correlation between EGI and the studied parameters were determined. SB presented
      the highest protein, lipid, ash, beta-glucan, total and insoluble dietary fiber
      contents; and the lowest non-resistant and total starch contents. The highest
      carbohydrate and resistant starch contents were in DSF and WSF, respectively.
      Phenolic compounds and antioxidant activities were concentrated in SB. The EGI
      values were: DSF 84.5 +/- 0.41; WSF 77.2 +/- 0.33; and SB 60.3 +/- 0.78. Phenolic
      compounds, specific flavonoids and antioxidant activities, as well as total,
      insoluble and soluble dietary fiber and beta-glucans of sorghum flour samples
      were all negatively correlated to EGI. RS content was not correlated to EGI.

PMID- 25766809
TI  - A study on starch profile of rajma bean (Phaseolus vulgaris) incorporated noodle
      dough and its functional characteristics.
AB  - Starch profile reflects functional characteristics like digestibility and product
      quality. A study was aimed to incorporate rajma in noodle processing to improve
      product and nutritional quality and also to reduce starch digestibility. It is
      known that some of the pulses like Kidney beans have an isoforms of Starch
      Branching-Enzyme (SBE) helps in converting amylose to amylopectin. Rajma flour
      was incorporated at 10%, 20% and 30% with Triticumdurum and subjected to
      rheological, physico-chemical and amylose/amylopectin determination using High
      Performance-Size-Exclusion-Chromatography (HPSEC). Results revealed that rajma
      flour decreased peak-viscosity from 954 to 683 BU and increased water absorption.
      Protein and dietary fiber content increased significantly. Sensory profile showed
      higher overall quality (>8.5). In vitro starch digestibility reduced from 65% to
      49%. Starch profile from HPSEC showed changes in amylose:amylopectin peak, this
      may be because of the presence of SBE, further studies may be required to support
      the hypothesis.

PMID- 25766810
TI  - An investigation of Turkish honeys: their physico-chemical properties,
      antioxidant capacities and phenolic profiles.
AB  - This study investigated some physico-chemical and biochemical characteristics of
      different honey types belonging to Turkish flora. Sixty-two honey samples were
      examined on the basis of pollen analyses, including 11 unifloral honeys
      (chestnut, heather, chaste tree, rhododendron, common eryngo, lavender, Jerusalem
      tea, astragalus, clover and acacia), two different honeydew honeys (lime and
      oak), and 7 different multifloral honeys. Electrical conductivity, moisture,
      Hunter color values, HMF, proline, diastase number, and sugar analyses of the
      honey samples were assessed for chemical characterization. Some phenolic
      components were analyzed by reverse phase high performance liquid chromatography
      (RP-HPLC) to determine honeys' phenolic profiles. Total phenolic compounds, total
      flavonoids, ferric reducing antioxidant capacity (FRAP) and 2,2-diphenyl-1
      picryhydrazyl (DPPH) free radical scavenging activity were measured as
      antioxidant determinants. The study results confirm that physico-chemical and
      biological characteristics of honeys are closely related to their floral sources,
      and that dark-colored honeys such as oak, chestnut and heather, have a high
      therapeutic potential. 

PMID- 25766811
TI  - Electrochemical fabrication of polymerized imidazole-based ionic liquid bearing
      pyrrole moiety for sensitive determination of hexestrol in chicken meat.
AB  - 1-[3-(tert-Butoxycarbonylamino)propyl]-3-[3-(N-pyrrole)propyl]imidazolium
      tetrafluoroborate [(t-Boc-APPPI)BF4], which is a novel pyrrolyl-functionalized
      ionic liquid, was synthesized and characterized. Subsequently, it was
      electrochemically deposited onto a glassy carbon electrode surface to fabricate a
      polymerized ionic liquid film electrode. X-ray photoelectron spectroscopy,
      scanning electron microscope and electrochemical impedance spectroscopy were used
      to confirm the successful polymerization of ionic liquid. Voltammetric behaviors
      of hexestrol at the film electrode were investigated. The oxidation peak slightly
      shifted towards positive potential, however, dramatically increased in peak
      current. Experimental conditions for hexestrol determination were optimized. The
      oxidation peak current is linear with hexestrol concentration in the range of 1.0
      * 10(-8)-1.0 * 10(-5) mol L(-1). The detection limit is estimated to be 2.1 * 10(
      9) mol L(-1) (S/N=3). Hexestrol in chicken meat was determined using the film
      electrode with good accuracy.

PMID- 25766812
TI  - Kinetics of immobilisation and release of tryptophan, riboflavin and peptides
      from whey protein microbeads.
AB  - This study investigated the kinetics of immobilisation and release of riboflavin,
      amino acids and peptides from whey microbeads. Blank whey microbeads were placed
      in solutions of the compounds. As the volume of microbeads added to the solution
      was increased, the uptake of the compounds increased, to a maximum of 95% for the
      pentapeptide and 56%, 57% and 45% for the dipeptide, riboflavin and tryptophan
      respectively, however, the rate of uptake remained constant. The rate of uptake
      increased with increasing molecule hydrophobicity. The opposite was observed in
      the release studies, the more hydrophobic compounds had lower release rate
      constants (kr). When whey microbeads are used as sorbents, they show excellent
      potential to immobilise small hydrophobic molecules and minimise subsequent
      diffusion, even in high moisture environments. 

PMID- 25766813
TI  - Electrochemical behavior and voltammetric determination of vanillin based on an
      acetylene black paste electrode modified with graphene-polyvinylpyrrolidone
      composite film.
AB  - The graphene-polyvinylpyrrolidone composite film modified acetylene black paste
      electrode (GR-PVP/ABPE) was fabricated and used to determine vanillin. In 0.1M
      H3PO4 solution, the oxidation peak current of vanillin increased significantly at
      GR-PVP/ABPE compared with bare ABPE, PVP/ABPE and GR/ABPE. The oxidation
      mechanism was discussed. The experimental conditions that exert influence on the
      voltammetric determination of vanillin, such as supporting electrolytes, pH
      values, accumulation potential and accumulation time, were optimized. Besides,
      the interference, repeatability, reproducibility and stability measurements were
      also evaluated. Under the optimal experimental conditions, the oxidation peak
      current was proportional to vanillin concentration in the range of 0.02-2.0 MUM,
      2.0-40 MUM and 40-100 MUM. The detection limit was 10nM. This sensor was used
      successfully for vanillin determination in various food samples.

PMID- 25766814
TI  - The effect of addition of skimmed milk on the characteristics of Myzithra
      cheeses.
AB  - Myzithra cheese is a traditional Greek whey cheese. Three types of Myzithra
      cheese were produced from A: 100% whey; B: 90% whey+10% ovine milk and C: 90%
      whey+10% skimmed ovine milk and were evaluated. The addition of skimmed milk to
      whey resulted in a new dietary product, containing 9.24% fat, with good quality,
      a harder texture and higher levels of ash, Ca, Mg and K than those of
      experimental cheeses A and B. Electrophoretic patterns and HPLC chromatograms of
      the proteins of Myzithra cheeses revealed the presence or not of alphas-CN to the
      whey cheeses. In addition, SDS-electrophoresis of proteins under special
      preparation of samples permitted for first time the separation of whey-cheese
      protein (WP) components that had been denatured during cooking of the whey. 

PMID- 25766815
TI  - Changes on grape phenolic composition induced by grapevine foliar applications of
      phenylalanine and urea.
AB  - Grapevines may require the input of nitrogen to grow and to guarantee an
      appropriate grape composition. Recently there has been a growing interest in
      foliar fertilization, which entails a fast and efficient assimilation of the
      products. The aim of this work was to study the influence of foliar applications
      of phenylalanine and urea, at two different doses, on grape anthocyanins,
      flavonols, flavan-3-ols, phenolic acids, and stilbenes. All treatments were
      applied at veraison and one week later at doses of 0.9 and 1.5 kg N/ha. The
      results showed that the synthesis of phenolic compounds was favoured by foliar
      applications of phenylalanine and urea. The application of the lowest dose of
      urea was the most effective treatment, increasing the content of several
      anthocyanins and flavonols. Moreover, none of the foliar treatments worsened the
      grape phenolic composition. In conclusion, foliar application of phenylalanine
      and especially urea, could be an interesting management tool for improving grape
      quality and their health-promoting properties.

PMID- 25766816
TI  - The effect of fermentation and addition of vegetable oil on resistant starch
      formation in wholegrain breads.
AB  - Resistant starch has potential health benefits but the factors affecting its
      formation in bread and baked products are not well studied. Here, the formation
      of resistant starch in wholemeal bread products was evaluated in relation to the
      processing conditions including fermentation time, temperature and the inclusion
      of palm oil as a vitamin source. The effects of each the factor were assessed
      using a full factorial design. The impact on final starch content of traditional
      sourdough fermentation of wholemeal rye bread, as well as the bulk fermentation
      process of wheat and wheat/oat blends of wholemeal bread, was also assessed by
      enzyme assay. Palm oil content was found to have a significant effect on the
      formation of resistant starch in all of the breads while fermentation time and
      temperature had no significant impact. Sourdough fermentation of rye bread was
      found to have a greater impact on resistant starch formation than bulk
      fermentation of wheat and wheat blend breads, most likely due the increased
      organic acid content of the sourdough process. 

PMID- 25766817
TI  - Trace analysis of Ponceau 4R in soft drinks using differential pulse stripping
      voltammetry at SWCNTs composite electrodes based on PEDOT:PSS derivatives.
AB  - Ponceau 4R, an edible synthetic colorant used in drinks, syrups, and sweets, has
      been successfully detected using differential pulse voltammetry at a single
      walled carbon nanotubes-modified composite electrode based on poly(3,4
      ethylenedioxythiophene):poly(styrene sulfonate) and two derivatives thereof. The
      electrochemical parameters of three Ponceau 4R sensors, such as pH value, pre
      concentration time, and scan rate, have been optimized, and their electrochemical
      performances have been compared. A poly(acrylate-modified 3,4
      ethylenedioxythiophene-co-3,4-ethylenedioxythiophene):poly(styrene sulfonate)
      single-walled carbon nanotubes-poly(vinyl alcohol)-modified electrode showed the
      best electrocatalytic activity, with the highest response current, lowest
      detection limit (1.8 nm), widest linear range (0.0055-110.6 MUm), and best
      sensing stability. Additionally, the modified electrode has also been
      successfully employed for real sample analysis with soft drinks. Satisfactory
      results were obtained, demonstrating this to be an easy and effective approach
      for trace analysis of Ponceau 4R in food samples.

PMID- 25766818
TI  - Identification and characterization of antioxidant peptides from chickpea protein
      hydrolysates.
AB  - Oxidative stress due to the excess of radical oxygen species (ROS) contribute to
      the development of different diseases. The use of antioxidants may prevent the
      development of these diseases by counteracting ROS levels. There is an increasing
      interest in natural antioxidants as they are safer for consumers than synthetic
      antioxidants. In this work, reducing power, free radical scavenging and cellular
      antioxidant activities of chickpea peptides fractions have been investigated.
      Peptide sequences included in fractions with antioxidant activity were
      identified. Main sequences, ALEPDHR, TETWNPNHPEL, FVPH and SAEHGSLH, corresponded
      to legumin, the main seed protein. Most peptides contained histidine, which has
      shown antioxidant activity. Two peptides also included tryptophan and
      phenylalanine, in which the phenolic group could also serve as hydrogen donor.
      These results show that legumin is a source of antioxidant peptides of high
      interest for food and pharmaceutical industries to develop new nutraceuticals and
      functional foods. 

PMID- 25766819
TI  - Green tea catechins reduced the glycaemic potential of bread: an in vitro
      digestibility study.
AB  - Green tea catechins are potent inhibitors of enzymes for carbohydrate digestion.
      However, the potential of developing low glycaemic index bakery food using green
      tea extract has not been investigated. Results of this study showed that addition
      of green tea extract (GTE) at 0.45%, 1%, and 2% concentration levels
      significantly reduced the glycaemic potential of baked and steamed bread. The
      average retention levels of catechins in the baked and steamed bread were 75.3
      89.5% and 81.4-99.3%, respectively. Bread fortified with 2% GTE showed a
      significantly lower level of glucose release during the first 90 min of
      pancreatic digestion as well as a lower content of rapidly digested starch (RDS)
      content. A significantly negative correlation was found between the catechin
      retention level and the RDS content of bread. The potential of transforming bread
      into a low GI food using GTE fortification was proven to be promising.

PMID- 25766820
TI  - Clarification of pomegranate juice with chitosan: changes on quality
      characteristics during storage.
AB  - In this study, for the first time, the use of chitosan as a clarifying agent in
      the production of clear pomegranate juice was evaluated and its effects on
      quality characteristics of juice were investigated. A central composite face
      centered design was used to establish the optimum conditions for clarification of
      pomegranate juice (PJ) using response surface methodology. The three factors were
      concentration of chitosan (10-120 mg/100ml), process temperature (10-20 degrees
      C), and process time (30-90 min) and their effects on turbidity and a(*) values
      were investigated. Using a desirability function method, the optimum process
      conditions were found to be 68.93 mg/100ml chitosan at a process temperature and
      time of 10 degrees C and 30 min, respectively. PJ was produced using the optimum
      conditions and the quality characteristics such as turbidity, colour
      characteristics (L(*), a(*), b(*), C(*)), titratable acidity, total phenolic,
      monomeric anthocyanin, and protein contents were evaluated during storage at 4
      and 20 degrees C for 6 months.

PMID- 25766821
TI  - Production of ready-to-eat lentil sprouts with improved antioxidant capacity:
      optimization of elicitation conditions with hydrogen peroxide.
AB  - This study evaluates the optimal conditions for elicitation with H2O2 for
      improving the antioxidant capacity of lentil sprouts. Generally, except for 3-day
      old sprouts, elicitation increased phenolic content (in respect to the control).
      The highest phenolic content was determined for 2-day-old sprouts treated with 15
      mM H2O2 (0.71 mg/gf.m.). All the studied modifications increased the antioxidant
      potential of sprouts. The highest elevation (3.2-fold) was found for 5-day-old
      sprouts (single 15 mM H2O2 treatment). A significant increase was also found on
      the 2nd and 4th days (2.13- and 2.14-fold, respectively). Elicitation induced
      tyrosine and phenylalanine ammonia-lyases activities. H2O2 treatments induced the
      activity of catalase - especially for 2-day-old sprouts treated with 150 mM H2O2
      (597 U/gf.m.). Elicitation with H2O2 is a useful tool for designing some features
      of sprouts. Phenolic content and antioxidant capacity are strongly affected by
      concentration of the elicitor, and time and intervals of its application.

PMID- 25766822
TI  - Pre-heating and polyphenol oxidase inhibition impact on extraction of purple
      sweet potato anthocyanins.
AB  - Purple sweet potatoes (PSP) have been used as a natural food colorant with high
      acylated anthocyanins concentrations. Commercially extracting pigments from PSP
      can be challenging due to firm texture and high polyphenol oxidase (PPO) content.
      These studies evaluated hot water immersions (30, 50, 70, and 90 degrees C for 10
      min) as pre-heating treatments and addition of PPO inhibitors (citric acid,
      oxalic acid, and sodium borate) to aqueous extraction solutions to aid pigment
      recovery. Predominant PSP anthocyanins included acylated cyanidin or peonidin
      derivatives. Non-pigmented cinnamates acted as oxidase substrates and induced co
      oxidation reactions with anthocyanins. Pre-heating PSP significantly increased
      polyphenolic yields in a temperature-dependent manner, consistent with tissue
      softening and PPO inactivation. The use of solvent modifiers in the extraction
      solution associated with heat helped minimize enzyme action and increased
      polyphenolic recovery. Minimizing the impact of PPO with heat was critical to the
      extraction and recovery of PSP anthocyanins, suitable for food use.

PMID- 25766823
TI  - Chlorogenic acid-mediated gel formation of oxidatively stressed myofibrillar
      protein.
AB  - The effect of chlorogenic acid (CA) at different concentration levels (0, 6, 30,
      and 150 MUmol/g protein) on porcine myofibrillar protein (MP) gelling potential
      in relation to chemical and structural changes was investigated. The results
      showed that CA generally inhibited protein carbonyl formation but did not prevent
      sulphydryl and amine losses caused by oxidation. The presence of CA intensified
      oxidation-initiated loss of alpha-helix conformation as well as tertiary
      structure of MP. CA at 150 MUmol/g produced the greatest increase in MP surface
      hydrophobicity and insolubility. The physicochemical changes with 6 and 30
      MUmol/g CA led to a remarkably enhanced gelling capacity of MP and augmented the
      positive effect of oxidation in building an elastic gel network. However, CA at
      150 MUmol/g was detrimental to the MP gelation. The result can explain why
      processed meats with phenolic-rich spices and herbs often exhibit variable
      texture-forming properties.

PMID- 25766824
TI  - Solubility and thermodynamic function of vanillin in ten different
      environmentally benign solvents.
AB  - The solubility of vanillin in ten different environmentally benign solvents
      namely water, ethanol, ethylene glycol (EG), ethyl acetate (EA), isopropanol
      (IPA), propylene glycol (PG), polyethylene glycol-400 (PEG-400), Transcutol,
      butanol-1 and butanol-2 was measured and correlated at T=(298-318)K. The
      resulting experimental data were correlated with the modified Apelblat and Van't
      Hoff models. Both the models showed good correlation of experimental solubility
      data with calculated ones with root mean square deviations in the range of (0.08
      1.55)%. The mole fraction solubility of vanillin was observed highest in PEG-400
      (4.29 * 10(-1) at 298 K) followed by Transcutol, EA, butanol-2, ethanol, EG, PG,
      IPA, butanol-1 and water from T=(298-318)K. The results of thermodynamic function
      in terms of dissolution enthalpy, Gibbs energy and dissolution entropy showed
      endothermic, spontaneous and entropy-driven dissolution of vanillin in all
      environmentally benign solvents.

PMID- 25766825
TI  - Comprehensive lipidome profiling of Sauvignon blanc grape juice.
AB  - This study presents a comprehensive lipidome analysis of Sauvignon blanc grape
      juice by combining GC-MS based fatty acid profiling with shotgun lipidomics
      strategy. We observed that despite grape juice being a water based matrix it
      contains a diverse range of lipid species, including common saturated and
      unsaturated free and intact fatty acids as well as odd-numbered and hydroxy fatty
      acids. Based on GC-MS quantitative data, we found that the total lipid content of
      grape juice could be as high as 2.80 g/L. The majority of lipids were present in
      the form of complex lipids with relatively small amount of free fatty acids
      (<15%). Therefore we concluded that the lipidome should be considered an
      important component of grape juice with the potential to impact on fermentation
      processes as well as on the sensorial properties of fermented products. This work
      serves as a hypothesis generating tool, the results of which justify follow-up
      studies to explore the influence of the grape juice lipidome and lipid metabolism
      in yeast on the aroma profile of wine.

PMID- 25766826
TI  - Electrostatic modulation and enzymatic cross-linking of interfacial layers
      impacts gastrointestinal fate of multilayer emulsions.
AB  - In this study, membrane properties were modulated using layer-by-layer
      electrostatic depositioning in combination with salt and/or enzyme treatment to
      control the gastrointestinal fate of emulsified oils. Lipid droplets coated by a
      single-layer of biopolymers (gelatin) were prepared by high pressure
      homogenization. Lipid droplets coated by a double-layer of biopolymers (gelatin
      pectin) were prepared by electrostatically depositing sugar beet pectin on the
      gelatin-coated droplets. Laccase was added to the double-layer emulsions to
      covalently crosslink the adsorbed pectin molecules, whereas sodium chloride was
      added to modulate interfacial properties through electrostatic screening effects.
      Non-cross-linked and cross-linked double-layer emulsions (with and without salt)
      were then passed through a simulated gastrointestinal tract (GIT) that included
      mouth, gastric and intestinal phases. Free fatty acid release profiles suggested
      that the stability of the emulsified droplets within the GIT played a more
      important role in determining the rate and extent of lipid digestion than the
      initial interfacial layer properties. 

PMID- 25766827
TI  - Improved evaporative light scattering detection for carbohydrate analysis.
AB  - Optimization and validation of evaporative light scattering detector (ELSD),
      aided by response surface methodology (RSM), has been developed for the liquid
      chromatography analysis of a wide molecular weight (MW) range of carbohydrates,
      including polysaccharides and oligosaccharides. Optimal experimental parameters
      for the ELSD detection were: 88.8 degrees C evaporator temperature, 77.9 degrees
      C nebulizer temperature and 1.1 standard litres per minute nitrogen flow rate.
      Optimal ELSD detection, used together with high performance size exclusion
      chromatography (HPSEC) of carbohydrates, gave a linear range from 250 to 1000 mg
      L(-1) (R(2)>0.998), with limits of detection and quantitation of 4.83-11.67 and
      16.11-38.91 mg L(-1), respectively. Relative standard deviation was lower than
      1.8% for intra-day and inter-day repeatability for apple pectin, inulin,
      verbascose, stachyose and raffinose. Recovery ranged from 103.7% to 118.3% for
      fructo-oligosaccharides, alpha-galacto-oligosaccharides and disaccharides.
      Optimized and validated ELSD detection is proposed for the analysis of high- to
      low-MW carbohydrates with high sensitivity, precision and accuracy.

PMID- 25766828
TI  - Model system-based mechanistic studies of black tea thearubigin formation.
AB  - Thearubigins are the most abundant pigments found in black tea, comprising
      polyphenolic oxidation products, whose composition and chemical nature have
      remained unresolved until recently. In the course of studying the mechanism of
      thearubigin formation from green tea flavan-3-ols, a model system, based on
      electrochemical oxidation of one of the main tea flavan-3-ol substrates,
      epigallocatechin gallate (EGCG), was employed. Reaction intermediates and
      products were subsequently analysed using mass spectrometry techniques, allowing
      for the identification of key intermediates and products. The results provided,
      for the first time, spectroscopic evidence for the structures of primary
      oxidation products, and led to the conclusion that oxidation is mainly taking
      place on the B-ring and the galloyl group, where the oxidized components undergo
      oxidative coupling for the formation of theaflavins, theasinensins and
      polyhydroxylated flavan-3-ols, all precursors for thearubigin formation.
      Furthermore, density functional theory (DFT) calculations were carried out to
      support key findings. 

PMID- 25766829
TI  - Determination of the phenolic composition from Brazilian tropical fruits by UHPLC
      MS/MS.
AB  - Although Brazil is the third largest fruit producer in the world, several
      specimens consumed are not well studied from the chemical viewpoint, especially
      for quantitative analysis. For this reason and the crescent employment of mass
      spectrometry (MS) techniques in food science we selected twenty-two phenolic
      compounds with important biological activities and developed an ultra-high
      performance liquid chromatography tandem mass spectrometry (UHPLC-MS/MS) method
      using electrospray (ESI) in negative ion mode aiming their quantification in
      largely consumed Brazilian fruits (acai-do-Amazonas, acerola, cashew apple, camu
      camu, pineapple and tapereba). Multiple reaction monitoring (MRM) was applied and
      the selection of proper product ions for each transition assured high
      selectivity. Linearity (0.995<r(2)<0.999), limit of detection (28.85-333.3
      pg/mL), limit of quantification (96.15-1111 pg/mL), inter- and intraday accuracy
      (>80%), precision (CV<20%) and extraction recovery rate (>80%) were satisfactory
      and showed that the method provides an efficient protocol to analyze phenolic
      compounds in fruit pulp extracts.

PMID- 25766830
TI  - Comparative study of transgenic and non-transgenic maize (Zea mays) flours
      commercialized in Brazil, focussing on proteomic analyses.
AB  - Genetically modified foods are a major concern around the world due to the lack
      of information concerning their safety and health effects. This work evaluates
      differences, at the proteomic level, between two types of crop samples:
      transgenic (MON810 event with the Cry1Ab gene, which confers resistance to
      insects) and non-transgenic maize flour commercialized in Brazil. The 2-D DIGE
      technique revealed 99 differentially expressed spots, which were collected in 2-D
      PAGE gels and identified via mass spectrometry (nESI-QTOF MS/MS). The abundance
      of protein differences between the transgenic and non-transgenic samples could
      arise from genetic modification or as a result of an environmental influence
      pertaining to the commercial sample. The major functional category of proteins
      identified was related to disease/defense and, although differences were observed
      between samples, no toxins or allergenic proteins were found. 

PMID- 25766831
TI  - Treatment with oleic acid reduces IgE binding to peanut and cashew allergens.
AB  - Oleic acid (OA) is known to bind and change the bioactivities of proteins, such
      as alpha-lactalbumin and beta-lactoglobulin in vitro. The objective of this study
      was to determine if OA binds to allergens from a peanut extract or cashew
      allergen and changes their allergenic properties. Peanut extract or cashew
      allergen (Ana o 2) was treated with or without 5mM sodium oleate at 70 degrees C
      for 60 min (T1) or under the same conditions with an additional overnight
      incubation at 37 degrees C (T2). After treatment, the samples were dialyzed and
      analyzed by SDS-PAGE and for OA content. IgE binding was evaluated by ELISA and
      western blot, using a pooled serum or plasma from individuals with peanut or
      cashew allergies. Results showed that OA at a concentration of 5mM reduced IgE
      binding to the allergens. Peanut sample T2 exhibited a lower IgE binding and a
      higher OA content (protein-bound) than T1. Cashew allergen T2 also showed a
      reduction in IgE binding. We conclude that OA reduces the allergenic properties
      of peanut extract and cashew allergen by binding to the allergens. Our findings
      indicate that OA in the form of sodium oleate may be potentially useful as a
      coating to reduce the allergenic properties of peanut and cashew allergens.

PMID- 25766832
TI  - Carotenoids in durian fruit pulp during growth and postharvest ripening.
AB  - Durian (Durio zibethinus) cvs. Chanee and Monthong fruit were severed from the
      tree during 14 day intervals, from 10 weeks after anthesis until commercial
      maturity. We determined the pulp (i.e. aril; fruit flesh) carotenoid composition,
      together with pulp firmness, color and total soluble solids (TSS) and postharvest
      quality. In ripe cv. Chanee fruit the main carotenoids were beta-carotene (about
      80%), and alpha-carotene (20%), with minor levels of lutein and zeaxanthin. In
      ripe fruit total carotenoid concentration (expressed per gram FW) was about 9
      fold higher in cv. Chanee than in cv. Monthong. Large differences between the
      cultivars were also found in beta-carotene levels (about 11 times more in cv.
      Chanee), and even larger ones in those of alpha-carotene. Differences in lutein
      and zeaxanthin concentrations were small. Pulp color was deeper yellow in cv.
      Chanee than in cv. Monthong, which was correlated with alpha-carotene and beta
      carotene concentrations. Durian contains a high fat percentage, which is
      conducive to carotenoid uptake. It is concluded that it is advisable to consume
      cv. Chanee rather than cv. Monthong if intake of carotenoids is considered
      important.

PMID- 25766833
TI  - Tea and soybean extracts in combination with milk fermentation inhibit growth and
      enterocyte adherence of selected foodborne pathogens.
AB  - This study examined the antibacterial and anti-adhesive properties of pure plant
      extracts (PPEs) of green tea (GT), black tea (BT) and soybean individually or in
      combination with milk. Fermented phenolic enriched-milk (fPEM) was prepared by
      combining PPEs with milk and fermented with lactic acid bacteria. Antimicrobial
      activity of extracts was evaluated by broth-dilution and agar diffusion assay.
      Anti-adhesive property of extracts was evaluated in Caco-2 cell model. Results
      from antibacterial tests showed that PPEs exhibited a dose-dependent growth
      inhibitory effect. Tea extracts were more effective in inhibiting Gram-positive
      bacteria while soybean extract exhibited similar effects against all pathogens
      tested. For fPEM, although total phenolic contents decreased compared with those
      in PPEs, growth inhibitory effect of fPEM containing tea extracts was greatly
      enhanced. All extracts showed significant inhibition against pathogen adhesion to
      Caco-2 cells. In particular, adhesion inhibition against Staphylococcus aureus
      and Listeria monocytogenes was >89% when fPEM extracts were applied. 

PMID- 25766834
TI  - Different autosomes evolved into sex chromosomes in the sister genera of Salix
      and Populus.
AB  - Willows (Salix) and poplars (Populus) are dioecious plants in Salicaceae family.
      Sex chromosome in poplar genome was consistently reported to be associated with
      chromosome XIX. In contrast to poplar, this study revealed that chromosome XV was
      sex chromosome in willow. Previous studies revealed that both ZZ/ZW and XX/XY sex
      determining systems could be present in some species of Populus. In this study,
      sex of S. suchowensis was found to be determined by the ZW system in which the
      female was the heterogametic gender. Gene syntenic and collinear comparisons
      revealed macrosynteny between sex chromosomes and the corresponding autosomes
      between these two lineages. By contrast, no syntenic segments were found to be
      shared between poplar's and willow's sex chromosomes. Syntenic analysis also
      revealed substantial chromosome rearrangements between willow's alternate sex
      chromatids. Since willow and poplar originate from a common ancestor, we proposed
      that evolution of autosomes into sex chromosomes in these two lineages occurred
      after their divergence. Results of this study indicate that sex chromosomes in
      Salicaceae are still at the early stage of evolutionary divergence. Additionally,
      this study provided valuable information for better understanding the genetics
      and evolution of sex chromosome in dioecious plants. 

PMID- 25766835
TI  - Serum klotho: relation to fibroblast growth factor-23 and other regulators of
      phosphate metabolism in children with chronic kidney disease.
AB  - FGF23 and Klotho synergize to regulate phosphate homeostasis by promoting renal
      phosphate excretion. Chronic kidney disease (CKD) may be viewed as a state of
      FGF23 resistance caused by Klotho deficiency. This viewpoint explains several
      observations on phosphate metabolism in CKD that lack mechanistic insights. Our
      objectives were to correlate serum klotho and FGF-23 with other variables that
      regulate phosphate metabolism. We studied 40 patients with CKD on conservative
      treatment (group A), 44 patients with end-stage renal disease (ESRD) on regular
      hemodialysis (group B), 40 kidney transplant recipients (KTR) (group C) and 40
      healthy controls for measuring serum klotho and FGF-23. Blood samples were
      withdrawn for measuring the levels of serum Calcium (Ca), Phosphorus (P),
      alkaline phosphatase (ALP), 1,25 (OH)2 D3, intact parathyroid hormone (PTH), FGF
      23 and alpha klotho. The mean levels of FGF-23 and alpha klotho in control group
      were 225.78 +/- 111.05 pg/ml (range: 102.4, 418.5) and 6.78 +/- 1.90 ng/ml
      (range: 4, 11), respectively. The mean levels of FGF-23 in the 3 studied groups
      were 1,034.2 +/- 84.6, 1,288.7 +/- 131.4 and 1,008.7 +/- 117.6 pg/ml,
      respectively. The median levels of s-klotho in the 3 studied groups were 3.15,
      2.3 and 2.95, respectively. It was found that FGF-23 was significantly increased
      and alpha klotho was significantly decreased in all patients when compared with
      those in the control group (p < 0.001, <0.001, respectively). We found that there
      was a significant inverse correlation between serum Ca and alpha klotho in the
      studied groups. There was no significant correlation between FGF-23 and alpha
      klotho in the studied groups (p > 0.05). We have shown that circulating s-klotho
      was not related to FGF-23 in CKD, dialysis and KTR patients. In addition, we
      demonstrated a novel association between serum Ca and s-klotho that needs to be
      further studied.

PMID- 25766836
TI  - Crizotinib resistance in acute myeloid leukemia with inv(2)(p23q13)/RAN binding
      protein 2 (RANBP2) anaplastic lymphoma kinase (ALK) fusion and monosomy 7.
AB  - This is the first report on the development of a p.G1269A mutation within the
      kinase domain (KD) of ALK after crizotinib treatment in RANBP2-ALK acute myeloid
      leukemia (AML). An elderly woman with AML with an inv(2)(p23q13)/RANBP2-ALK and
      monosomy 7 was treated with crizotinib. After a short-term hematological response
      and the restoration of normal hematopoiesis, she experienced a relapse of AML.
      Fluorescence in situ hybridization using the ALK break-apart probe confirmed the
      inv(2)(p23q13), while G-banded karyotyping revealed the deletion of a segment of
      the short arm of chromosome 1 [del(1)(p13p22)] after crizotinib therapy. The ALK
      gene carried a heterozygous mutation at the nucleotide position g.716751G>C
      within exon 25, causing the p.G1269A amino acid substitution within the ALK-KD.
      Reverse transcriptase PCR revealed that the mutated ALK allele was selectively
      transcribed and the mutation occurred in the ALK allele rearranged with RANBP2.
      As both the del(1)(p13p22) at the cytogenetic level and p.G1269A at the
      nucleotide level newly appeared after crizotinib treatment, it is likely that
      they were secondarily acquired alterations involved in crizotinib resistance.
      Although secondary genetic abnormalities in ALK are most frequently described in
      non-small cell lung cancers harboring an ALK alteration, this report suggests
      that an ALK-KD mutation can occur independently of the tumor cell type or fusion
      partner after crizotinib treatment.

PMID- 25766837
TI  - Exploring the link between scavenger receptor B1 expression and chronic
      obstructive pulmonary disease pathogenesis.
AB  - Chronic obstructive pulmonary disease (COPD) has been recognized as one of the
      major causes of morbidity and mortality in the United States; it is the third
      leading cause of deaths in the United States, with approximately 15 million
      Americans affected with COPD. Although exposure to cigarette smoke has been shown
      to be the main, if not the only, risk factor for COPD, the mechanisms underlying
      this association remain unclear. Most smokers do not develop COPD, suggesting
      that a combination of exposure and susceptibility (genetic background) is
      required. Several mechanisms contribute to the pathogenesis of COPD, such as
      influx of inflammatory cells into the lung, imbalance between proteolytic and
      antiproteolytic molecules, disruption of the balance between apoptosis and
      replenishment of structural cells in the lung, and disruption of
      oxidant/antioxidant balance. The scavenger receptor BI (SRB1) plays an important
      role in mediating the uptake of high-density lipoprotein (HDL)-derived
      cholesterol and cholesteryl ester in tissues. In addition to its role as the HDL
      receptor, SRB1 is also involved in pathogen recognition, identification of
      apoptotic cells, tissue antioxidant uptake (tocopherol and carotenoids), and lung
      surfactant composition, all factors involved in COPD pathogenesis. Therefore, it
      is possible that lung SRB1 levels are involved in the development of COPD.

PMID- 25766840
TI  - Benzodiazepine use and aggressive behaviour.

PMID- 25766838
TI  - Inhibition of lethal inflammatory responses through the targeting of membrane
      associated Toll-like receptor 4 signaling complexes with a Smad6-derived peptide.
AB  - We have previously reported that Smad6, one of the inhibitory Smads of
      transforming growth factor-beta (TGF-beta)/bone morphogenetic protein (BMP)
      signaling, inhibits Toll-like receptor (TLR) 4 signaling by disrupting the
      Pellino-1-mediated TLR4 signaling complex. Here, we developed Smaducin-6, a novel
      membrane-tethered palmitic acid-conjugated Smad6-derived peptide composed of
      amino acids 422-441 of Smad6. Smaducin-6 interacted with Pellino-1, located in
      the inner membrane, thereby disrupting the formation of IRAK1-, RIP1-, IKKepsilon
      mediated TLR4 signaling complexes. Systemic administration of Smaducin-6 showed a
      significant therapeutic effect on mouse TLR4-mediated inflammatory disease
      models, cecal-ligation-puncture (CLP)-induced sepsis, and lipopolysaccharide
      induced endotoxemia, by inhibiting pro-inflammatory cytokine production and
      apoptosis while enhancing neutrophil migration and bacterial clearance. Our
      findings provide clues to develop new peptide-based drugs to target Pellino-1
      protein in TLR4 signaling pathway for the treatment of sepsis.

PMID- 25766839
TI  - Attention Stabilizes Representations in the Human Hippocampus.
AB  - Attention and memory are intricately linked, but how attention modulates brain
      areas that subserve memory, such as the hippocampus, is unknown. We hypothesized
      that attention may stabilize patterns of activity in human hippocampus, resulting
      in distinct but reliable activity patterns for different attentional states. To
      test this prediction, we utilized high-resolution functional magnetic resonance
      imaging and a novel "art gallery" task. On each trial, participants viewed a room
      containing a painting, and searched a stream of rooms for a painting from the
      same artist (art state) or a room with the same layout (room state). Bottom-up
      stimulation was the same in both tasks, enabling the isolation of neural effects
      related to top-down attention. Multivariate analyses revealed greater pattern
      similarity in all hippocampal subfields for trials from the same, compared with
      different, attentional state. This stability was greater for the room than art
      state, was unrelated to univariate activity, and, in CA2/CA3/DG, was correlated
      with behavior. Attention therefore induces representational stability in the
      human hippocampus, resulting in distinct activity patterns for different
      attentional states. Modulation of hippocampal representational stability
      highlights the far-reaching influence of attention outside of sensory systems. 

PMID- 25766841
TI  - Synthesis of chitin and chitosan stereoisomers by thermostable alpha-glucan
      phosphorylase-catalyzed enzymatic polymerization of alpha-D-glucosamine 1
      phosphate.
AB  - The relationship between two aminopolysaccharide stereoisomers, namely alpha-(1
      >4)- and beta-(1->4)-linked (N-acetyl)-D-glucosamine polymers, is of significant
      interest within the field of polysaccharide science, as they correspond to amino
      analogs of the representative abundant natural polysaccharides, viz. amylose and
      cellulose. While the latter glucosamine polymer is the basis of well-known
      natural polysaccharides, chitin and chitosan (linear polysaccharides composed of
      beta-(1->4)-linked N-acetyl-D-glucosamine and D-glucosamine), to the best of our
      knowledge, the former (alpha-(1->4)-linked) has not been observed in nature. For
      the purpose of these studies, the synthesis of such non-natural
      aminopolysaccharides was performed by the thermostable alpha-glucan phosphorylase
      (from Aquifex aeolicus VF5)-catalyzed enzymatic polymerization of alpha-D
      glucosamine 1-phosphate (GlcN-1-P), via successive alpha-glucosaminylations, in
      ammonia buffer containing Mg(2+) ions, resulting in the production of the alpha
      (1->4)-linked D-glucosamine polymers, corresponding to the structure of the
      chitosan stereoisomer. Subsequent N-acetylation of the products gave the
      aminopolysaccharides, corresponding to the chitin stereoisomer.

PMID- 25766843
TI  - Genotyping and immunohistochemistry of gastrointestinal stromal tumors: An
      update.
AB  - Gastrointestinal stromal tumors (GISTs) were originally thought to harbor either
      KIT or platelet-derived growth factor receptor A (PDGFRA) mutations only.
      However, more recent discoveries have highlighted additional, less common
      oncogenic driver mutations including NF1, BRAF, and succinate dehydrogenase (SDH)
      mutations. Genotyping GISTs has become more important since not all genotypes
      respond equally to FDA-approved tyrosine kinase inhibitors. GIST is a paradigm
      for personalized cancer therapy. Recent studies demonstrate how
      immunohistochemistry can be used both to diagnose GIST and to screen for specific
      mutations. DOG1 is particularly useful in the diagnosis of KIT-negative GIST,
      including tumors with PDGFRA mutations, which can also potentially be identified
      by immunohistochemistry for PDGFRA. SDHB immunohistochemistry is useful in
      characterizing GISTs with SDHA-D mutations, whereas SDHA immunohistochemistry is
      able to identify SDHA mutant GISTs. 

PMID- 25766842
TI  - Multidisciplinary neoadjuvant management for potentially curable pancreatic
      cancer.
AB  - Pancreatic adenocarcinoma remains the fourth leading cause of cancer mortality in
      the U.S. Despite advances in surgical technique, radiotherapy technologies, and
      chemotherapeutics, the 5-year survival rate remains approximately 20% for the 15%
      of patients who are eligible for surgical resection. The majority of this group
      suffers metastatic recurrence. However, despite advances in therapies for
      patients with advanced pancreatic cancer, only surgery has consistently proven to
      improve long-term survival. Various combinations of chemotherapy, biologic
      targeted therapy, and radiotherapy have been evaluated in different settings to
      improve outcomes. In this context, a neoadjuvant (preoperative) treatment
      strategy offers numerous potential benefits: (1) ensuring delivery of early,
      systemic therapy, (2) improving selection of patients for surgical therapy with
      truly localized disease, (3) potential downstaging of the neoplasm facilitating a
      negative margin resection in patients with locally advanced disease, and (4)
      providing a superior clinical trial mechanism capable of rapid assessment of the
      efficacy of novel therapeutics. This article reviews the recent trends in the
      management of pancreatic adenocarcinoma, with a particular emphasis on a
      multidisciplinary neoadjuvant approach to treatment. 

PMID- 25766845
TI  - Brain training, exercise, and healthy eating slow cognitive decline in elderly
      people at risk, study finds.

PMID- 25766844
TI  - LS-VISM: A software package for analysis of biomolecular solvation.
AB  - We introduce a software package for the analysis of biomolecular solvation. The
      package collects computer codes that implement numerical methods for a
      variational implicit-solvent model (VISM). The input of the package includes the
      atomic data of biomolecules under consideration and the macroscopic parameters
      such as solute-solvent surface tension, bulk solvent density and ionic
      concentrations, and the dielectric coefficients. The output includes estimated
      solvation free energies and optimal macroscopic solute-solvent interfaces that
      are obtained by minimizing the VISM solvation free-energy functional among all
      possible solute-solvent interfaces enclosing the solute atoms. We review the VISM
      with various descriptions of electrostatics. We also review our numerical methods
      that consist mainly of the level-set method for relaxing the VISM free-energy
      functional and a compact coupling interface method for the dielectric Poisson
      Boltzmann equation. Such numerical methods and algorithms constitute the central
      modules of the software package. We detail the structure of the package, format
      of input and output files, workflow of the codes, and the postprocessing of
      output data. Our demo application to a host-guest system illustrates how to use
      the package to perform solvation analysis for biomolecules, including ligand
      receptor binding systems. The package is simple and flexible with respect to
      minimum adjustable parameters and a wide range of applications. Future extensions
      of the package use can include the efficient identification of ligand binding
      pockets on protein surfaces.

PMID- 25766846
TI  - Cytological Diagnoses of Adenocarcinoma in situ of the Cervix: Common
      Misdiagnoses.
AB  - OBJECTIVE: In routine screening, glandular lesions have high false-negative and
      false-positive rates. Our study sought to improve the cytological diagnoses and
      differentiation of glandular lesions. STUDY DESIGN: A total of 24 cytology slides
      were retrospectively reviewed. Among these slides, 15 were confirmed via
      histology to have varying amounts of adenocarcinoma in situ (AIS) components. The
      other 9 cytology slides exhibited AIS mimics that had been originally considered
      to be AIS or atypical glandular cells (AGCs) and were selected for
      differentiation from AIS. RESULTS: Overall, 12 of the 15 cytological slides
      exhibited significant atypical glandular features that met the criteria for AIS.
      However, the original cytological diagnoses included 2 cases of AIS, 3 AGCs-favor
      neoplasia (AGC-FN), 2 AGCs, 1 case that was not otherwise specified (AGC-NOS), 1
      NILM (negative for intraepithelial lesion and malignancy), 3 HSILs (high-grade
      squamous intraepithelial lesions), and 2 ASC-Hs (atypical squamous cells, cannot
      exclude HSIL). The latter 9 cytological slides were subsequently histologically
      confirmed to be 2 metaplasias, 2 reactive lesions, 1 decidual change, 3 serous
      adenocarcinomas, and 1 SCNEC (small-cell neuroendocrine carcinoma). CONCLUSION:
      Cytological screening will be valuable for identifying glandular lesions as
      effectively as squamous lesions if the doubly high false rates can be decreased.

PMID- 25766847
TI  - Emerging concepts in the therapy of mitochondrial disease.
AB  - Mitochondrial disorders are an important group of genetic conditions
      characterized by impaired oxidative phosphorylation. Mitochondrial disorders come
      with an impressive variability of symptoms, organ involvement, and clinical
      course, which considerably impact the quality of life and quite often shorten the
      lifespan expectancy. Although the last 20 years have witnessed an exponential
      increase in understanding the genetic and biochemical mechanisms leading to
      disease, this has not resulted in the development of effective therapeutic
      approaches, amenable of improving clinical course and outcome of these conditions
      to any significant extent. Therapeutic options for mitochondrial diseases still
      remain focused on supportive interventions aimed at relieving complications.
      However, new therapeutic strategies have recently been emerging, some of which
      have shown potential efficacy at the pre-clinical level. This review will present
      the state of the art on experimental therapy for mitochondrial disorders.

PMID- 25766848
TI  - High resolution separation of recombinant monoclonal antibodies by size-exclusion
      ultra-high performance liquid chromatography (SE-UHPLC).
AB  - Size-exclusion chromatography (SEC) is an important mode of separation used in
      monoclonal antibody (mAb) characterization and quality control. SEC separates
      mAbs into three major species: high molecular weight species, main peak
      (predominantly monomer), and low molecular weight species. However, mAb SEC
      separations have low resolution between the different sized species, and the
      analysis is slow with low sample throughput. The introduction of size-exclusion
      ultra-high performance liquid chromatography (SE-UHPLC) columns offers a new
      opportunity to improve both the resolution and throughput of SEC analysis. This
      study demonstrates that SE-UHPLC columns deliver better resolution of size
      variants in a shorter period of time than conventional SEC columns. For example,
      an SE-UHPLC column 300-mm in length produced separation of mAb Fab/c fragments in
      less than 10min, in comparison to a conventional SEC column output, where these
      fragments co-elute with the main peak. Furthermore, we observed that high back
      pressure does not generate HMWS under optimized mobile phase conditions for mAbs.
      The platform SE-UHPLC method has been demonstrated to be suitable for the
      analysis of multiple mAbs, with greatly improved sample throughput and peak
      resolution of mAb size variants.

PMID- 25766849
TI  - Characterization and quantification of the chemical compositions of Scutellariae
      Barbatae herba and differentiation from its substitute by combining UHPLC-PDA
      QTOF-MS/MS with UHPLC-MS/MS.
AB  - The aim of this study was to investigate the possibility of using the non
      official species Scutellaria indica L. as the substitute for the official species
      Scutellaria barbata D. Don. A sensitive, precise and accurate method was
      developed to identify their chemical compositions from the crude extracts using
      UHPLC-PDA-QTOF-MS/MS. 36 peaks were detected and 28 peaks have been tentatively
      and structurally characterized by comparing their retention times, UV spectra and
      HR-MS data with those of the reference substances and/or the data of the
      literatures. Additionally, 5 flavonoids have been quantified by multiple reaction
      monitoring (MRM) in the negative ionization mode. The results demonstrated that
      there were 23 common peaks between these two species. However, the other 13 peaks
      from S. barbata could not be detected in S. indica. Furthermore, the content of 5
      flavonoids is significantly different. Scutellarein cannot be detected in S.
      indica, which was considered as the characteristic component for distinguishing
      the two species. Our data, therefore, clearly demonstrate that S. indica may not
      be used as the substitute for S. barbata and further investigation is needed to
      determine through investigation of their therapeutic efficacy.

PMID- 25766850
TI  - Concurrent quantification and comparative pharmacokinetic analysis of bioactive
      compounds in the Herba Ephedrae-Semen Armeniacae Amarum herb pair.
AB  - The Mahuang-Xingren herb-pair (MX), the combination of Herba Ephedrae (Mahuang in
      Chinese) and Semen Armeniacae Amarum (Xingren in Chinese), is a classical
      combination used in traditional Chinese Medicine to treat asthma and bronchitis.
      A simple and reliable ultra-performance liquid chromatography-tandem mass
      spectrometry method was developed to simultaneously quantify and compare the
      pharmacokinetics of 5 ephedra alkaloids and epimers of amygdalin and prunasin in
      rat plasma after oral administration of Mahuang, Xingren, and MX aqueous
      extracts. Samples were pretreated by a single-step protein precipitation with
      acetonitrile, and diphenhydramine hydrochloride and puerarin were used as
      internal standards. Pharmacokinetic parameters were investigated using DAS 3.2.2
      (Mathematical Pharmacology Professional Committee of China, Shanghai, China). The
      validated method demonstrated adequate sensitivity, selectivity, and process
      efficiency for the bioanalysis of 8 compounds, including 3 pairs of epimers. MX
      administration improved the bioavailability of amygdalin and prunasin.
      Furthermore, MX facilitated intake of lower doses of ephedra alkaloids and
      increased elimination rates in comparison with Mahuang alone. These results
      illustrate the rationale behind the preferred use of the combination of Mahuang
      and Xingren. To our knowledge, this is the first report of stereo-selective
      metabolism of amygdalin. Further, the metabolic mechanism underlying this
      phenomenon merits future research attention.

PMID- 25766851
TI  - Effect of sample preparation on components and liver toxicity of Polygonum
      multiflorum.
AB  - It was shown that different extracts had significant differences in the toxicity
      of Polygonum multiflorum. In this study, the effect of sample preparation on
      components and liver toxicity of different extracts from P. multiflorum were
      determined. Hepatoxic components were discovered based on biomembrane extraction.
      Comparative chemistry and toxicology between ethanol and water extracts were also
      performed. The results showed that ethanol extract had much stronger
      hepatotoxicity, the content of emodin-8-O-beta-d-glucopyranoside, physcion-8-O
      beta-d-glucopyranoside, emodin and physcion was significantly higher in ethanol
      extract than in water extract, while the human hepatocytes extraction showed that
      2,3,5,4'-tetrahydroxystilbene-2-O-beta-d-glucopyranoside, emodin-8-O-beta-d
      glucopyranoside, physcion-8-O-beta-d-glucopyranoside, emodin and physcion had
      interaction with human hepatocytes. The hepatotoxic effect of these components
      was investigated on human hepatocytes LO2 cells and emodin-8-O-beta-d
      glucopyranoside, physcion-8-O-beta-d-glucopyranoside, emodin and physcion were
      finally confirmed to be, at least partial, hepatotoxic components. The results
      showed that sample preparation has significant effect on components in extracts
      of P. multiflorum especially the components related to hepatotoxicity. Water
      extract, the conventional administration form of Chinese herbs, is prefer for
      phytotherapy before well understanding their chemistry and biological activities.

PMID- 25766852
TI  - Evaluation of a Telehealth Service for COPD and HF patients: Clinical outcome and
      patients' perceptions.
AB  - NHS Croydon Health Services and NHS Croydon Clinical Commissioning Group have
      been providing telehealth services for the past 36 months. The aim of this study
      was to measure the impact of telehealth when implemented as a service within a
      standard patient care pathway. To measure the clinical outcomes, the number of
      A&E visits and hospital admissions, recorded on the NHS Secondary Uses Service
      database, were compared before and after the implementation of the telehealth
      service. The number of all events despite its cause and the number of events
      related to the patients' diagnosed condition were collected. To elicit patients'
      perceptions about the telehealth service, a cross sectional survey of patients
      registered on the triage manager database was used to explore their perceptions,
      concerns and general satisfaction with the telehealth service via a 4 point
      likert scale questionnaire. The data of 48 patients were collected and telehealth
      reduced the number of both A&E and hospital admission due to all causes by 13% (P
      = 0.42) and 22% (P = 0.048), respectively. When only the events directly related
      to the patient's diagnosed condition were considered, a reduction by 36% (P =
      0.03) and 28% (P = 0.02) was recorded for A&E visits and hospital admission
      respectively. 27 patients consented to participate in the survey. Overall,
      patients were very satisfied with telehealth services. Patients agreed that
      telehealth had improved their health, it was a convenient form of health care
      delivery for them and they were more involved in the decisions about their care
      or treatment. In addition, since being on telehealth, patients' confidence in
      managing their health increased from somewhat confident to confident. Telehealth,
      when provided as a service within a standard care pathway, seems to decrease
      hospital admissions and A&E visits. Good patient satisfaction suggests that the
      current service is accepted and it could be further expanded to include a larger
      number of patients.

PMID- 25766853
TI  - A comparison of telemedicine teaching to in-person teaching for the acquisition
      of an ultrasound skill - a pilot project.
AB  - Telemedicine is widely used for medical education but few studies directly
      investigate how telemedicine teaching compares to conventional in-person
      teaching. Here we determine whether telemedicine teaching is as effective as in
      person teaching for the acquisition of an ultrasound skill important in trauma
      care. Nurses with no prior ultrasound experience (n = 10) received study material
      and a teaching session on how to locate and image the hepatorenal space
      (Morison's pouch). One group of nurses was taught in-person (In-person Group) and
      the other group was taught via telemedicine (Telemedicine Group). Telemedicine
      allowed two-way audio and visual communication between the instructor and the
      nurses. A comparison of the teaching techniques showed that telemedicine teaching
      was equivalent to in-person teaching for the acquisition of practical and
      theoretical skills required to locate Morison's pouch. The average time required
      to locate Morison's pouch after teaching was similar between both groups. The
      results demonstrate that telemedicine teaching is as effective as in-person
      teaching for the acquisition of bedside ultrasound skills necessary to identify
      Morison's pouch. Remote teaching of these bedside ultrasound skills may help in
      the diagnosis of intra-abdominal bleeding in rural healthcare centers. 

PMID- 25766854
TI  - Point-of-care monitoring of warfarin treatment in community dwelling elderly--A
      randomised controlled study.
AB  - The objective of this study was to assess clinical effectiveness and costs of
      launching point-of-care monitoring of warfarin treatment in community dwelling
      frail elderly patients. A prospective multicentre controlled randomised study
      over 12 months comparing a point-of-care strategy with usual monitoring routines
      was carried out in primary healthcare centres and anticoagulation clinics in
      southeast Sweden. The subjects were community dwelling elderly across rural
      southeast Sweden on chronic warfarin treatment. Main outcome measures were time
      in therapeutic range (TTR), rate of treatment-related adverse events and costs.
      The study comprised 103 elderly people (61% women) mean age 86 yrs (range 75-98)
      treated with warfarin for median 9 yrs (range 1-18). Patients randomised to start
      point-of-care monitoring (n = 55) showed 75.9% in TTR before trial vs. 72.6%
      during trial (ns). The patients randomised to continue on usual monitoring
      routines (n = 48) showed 75.2% in TTR prior to trial vs. 72.9% during trial (ns).
      The point-of-care monitoring showed potential savings of SEK 624 per patient
      annually (based partly on effects that were not statistically significant). The
      study shows that point-of-care monitoring of warfarin treatment in community
      dwelling elderly in rural areas is as effective as usual monitoring routines and
      that it may offer savings to society.

PMID- 25766855
TI  - If home telemonitoring reduces mortality in heart failure, is this just due to
      better guideline-based treatment?
AB  - To investigate, in a 'real-world' setting, the impact of home telemonitoring
      (HTM) compared to usual care on achieved dose of guideline-recommended
      medication, hospitalisation rate and mortality in patients with heart failure
      (HF). METHODS: We retrospectively analyzed data on 333 patients with HF referred
      to a HTM service supported by a nurse-specialist (mean age 71+/-12 years, mean
      left ventricular ejection fraction (LVEF) 36 +/- 11% and median N-Terminal pro B
      type Natriuretic Peptide (NT-proBNP) 2,972 ng/L (interquartile range (IQR): 1,447
      7,801 ng/L)). Most patients (n = 278) accepted HTM (HTM-group) but 55 refused and
      received usual care (UC-group). In the HTM-group, weight, heart rate, blood
      pressure and symptom severity were measured daily. RESULTS: At referral,
      respectively 90%, 90%, 67% and 94% of patients with LVEF <=40% (n = 229) were
      treated with beta-blockers (BB), angiotensin converting enzyme-inhibitors (ACE-I)
      or angiotensin receptor blockers (ARB), mineralocorticoid receptor antagonists
      (MRA) and diuretics, with rates similar between groups. After 6 months,
      prescription of BB (92% vs 83%), ACE-I/ARB (92% vs 90%) and MRA (68% vs 67%) did
      not differ significantly between groups. The proportions of patients who achieved
      >=50% and >=100% of target doses of BB, ACE-I/ARB and MRA were also similar in
      each group. However, during a median follow-up of 1094 days (IQR 767-1419) fewer
      patients who chose HTM died (33% vs 49%; P = 0.002). CONCLUSION: Patients who
      choose HTM have a better prognosis than those who do not but this does not appear
      to be mediated through greater prescription of key HF medications.

PMID- 25766856
TI  - Investigating the quality of video consultations performed using fourth
      generation (4G) mobile telecommunications.
AB  - The use of fourth-generation (4G) mobile telecommunications to provide real-time
      video consultations were investigated in this study with the aims of determining
      if 4G is a suitable telecommunications technology; and secondly, to identify if
      variation in perceived audio and video quality were due to underlying network
      performance. Three patient end-points that used 4G Internet connections were
      evaluated. Consulting clinicians recorded their perception of audio and video
      quality using the International Telecommunications Union scales during clinics
      with these patient end-points. These scores were used to calculate a mean opinion
      score (MOS). The network performance metrics were obtained for each session and
      the relationships between these metrics and the session's quality scores were
      tested. Clinicians scored the quality of 50 hours of video consultations,
      involving 36 clinic sessions. The MOS for audio was 4.1 +/- 0.62 and the MOS for
      video was 4.4 +/- 0.22. Image impairment and effort to listen were also rated
      favourably. There was no correlation between audio or video quality and the
      network metrics of packet loss or jitter. These findings suggest that 4G networks
      are an appropriate telecommunication technology to deliver real-time video
      consultations. Variations in quality scores observed during this study were not
      explained by the packet loss and jitter in the underlying network. Before
      establishing a telemedicine service, the performance of the 4G network should be
      assessed at the location of the proposed service. This is due to known
      variability in performance of 4G networks. 

PMID- 25766857
TI  - TulaSalud: An m-health system for maternal and infant mortality reduction in
      Guatemala.
AB  - The Guatemalan NGO (Non-Governmental Organization) TulaSalud has implemented an m
      health project in the Department of Alta Verapaz. This Department has 1.2 million
      inhabitants (78% living in rural areas and 89% from indigenous communities) and
      in 2012, had a maternal mortality rate of 273 for every 100,000 live births. This
      m-health initiative is based on the provision of a cell phone to community
      facilitators (CFs). The CFs are volunteers in rural communities who perform
      health prevention, promotion and care. Thanks to the cell phone, the CFs have
      become tele-CFs who able to carry out consultations when they have questions;
      send full epidemiological and clinical information related to the cases they
      attend to; receive continuous training; and perform activities for the prevention
      and promotion of community health through distance learning sessions in the
      Q'eqchi and/or Poqomchi' languages. In this study, rural populations served by
      tele-CFs were selected as the intervention group while the control group was
      composed of the rural population served by CFs without Information and
      Communication Technology (ICT) tools. As well as the achievement of important
      process results (116,275 medical consultations, monitoring of 6,783 pregnant
      women, and coordination of 2,014 emergency transfers), the project has
      demonstrated a statistically significant decrease in maternal mortality (p <
      0.05) and in child mortality (p = 0.054) in the intervention group compared with
      rates in the control group. As a result of the telemedicine initiative, the
      intervention areas, which were selected for their high maternal and infant
      mortality rates, currently show maternal and child mortality indicators that are
      not only lower than the indicators in the control area, but also lower than the
      provincial average (which includes urban areas).

PMID- 25766858
TI  - Should Infant Formula Provide Both Omega-3 DHA and Omega-6 Arachidonic Acid?

PMID- 25766859
TI  - A novel Schistosoma japonicum endonuclease homologous to DNase II.
AB  - BACKGROUND: Recent advances in studies of the Schistosoma japonicum genome have
      opened new avenues for the elucidation of parasite biology and the identification
      of novel targets for vaccines, drug development and early diagnostic tools.
      RESULTS: In this study, we surveyed the S. japonicum genome database for genes
      encoding nucleases. A total of 130 nucleases of 3 classes were found.
      Transcriptional analysis of these genes using a genomic DNA microarray revealed
      that the majority of the nucleases were differentially expressed in parasites of
      different developmental stages or different genders, whereas no obvious
      transcriptional variation was detected in parasites from different hosts. Further
      analysis of the putative DNases of S. japonicum revealed a novel DNase II
      homologue (Sjda) that contained a highly conserved catalytic domain. A
      recombinant Sjda-GST protein efficiently hydrolysed genomic DNA in the absence of
      divalent iron. Western-blot and immunofluorescence assays showed that Sjda was
      mainly expressed on the teguments of female adult parasites and induced early
      humoral immune responses in infected mice. CONCLUSIONS: A novel DNase II
      homologue, Sjda, was identified in S. japonicum. Sjda was mainly distributed on
      the teguments of adult female parasites and possessed a typical divalent iron
      independent DNA catalytic activity. This protein may play an important role in
      the host-parasite interaction.

PMID- 25766860
TI  - Down-regulation of suppressor of cytokine signaling 3 by miR-122 enhances
      interferon-mediated suppression of hepatitis B virus.
AB  - MicroRNA-122 (miR-122) is involved in the pathogenesis of several liver diseases,
      including chronic hepatitis B infection and hepatocellular carcinoma. This study
      aimed to explore the potential role of miR-122 in the interferon (IFN)-mediated
      suppression of hepatitis B virus (HBV) in hepatocytes. We found that elevated
      expression of suppressor of cytokine signaling 3 (SOCS3) following HBV infection,
      contributed to the inactivation of the IFN signaling pathway. Based on previous
      studies from our laboratory showing that miR-122 can modulate type I IFN
      expression by inhibiting SOCS1 expression, we analyzed the SOCS3 mRNA sequence
      for putative miR-122 binding sites. We demonstrate that miR-122 inhibits SOCS3
      expression by targeting the 3'-untranslated region of the SOCS3 mRNA within the
      region 1887-1910 nucleotides. Finally, we demonstrate that significantly
      increased levels of IFN lead to decreased HBV expression in miR-122 mimic-treated
      Huh7 cells, whereas inhibition of endogenous miR-122 leads to enhanced viral
      production, owing to a marked decrease in IFN expression. Taken together, our
      results demonstrate that miR-122 down-regulates SOCS3, thus positively affecting
      the anti-HBV efficiency of endogenous type I IFN. Our study suggests that
      suppression of miR-122 induced by HBV infection, leads to the inactivation of IFN
      expression, which in turn enhances HBV replication, contributing to viral
      persistence and hepatocarcinogenesis. 

PMID- 25766861
TI  - Increased risk of non-AIDS-related events in HIV subjects with persistent low CD4
      counts despite cART in the CoRIS cohort.
AB  - The aim was to analyze clinical complications in HIV-infected subjects who
      persistently maintain low CD4 levels despite virological response to cART in the
      Spanish CoRIS cohort. The main inclusion criteria were CD4 counts <200cells/mm(3)
      at cART-initiation and at least 2years under cART achieving a viral load
      <500copies/mL. Those patients with CD4 counts <250cells/mm(3) 2years after cART
      were classified as the Low-CD4 group, and clinical events were collected from
      this time-point. Poisson regression models were used to calculate incidence rate
      ratios of death, AIDS-defining events, serious non-AIDS-defining events (NAE) and
      of each specific NAE category (non-AIDS-defining malignancies (non-ADM),
      cardiovascular, kidney- and liver-related events). Of 9667 patients in the
      cohort, a total of 1128 met the criteria and 287 (25.4%) were classified in the
      Low-CD4 group. A higher risk of death (aIRR: 4.71; 95% CI: 1.88-11.82; p
      value=0.001) and of non-ADM were observed in this group (aIRR: 2.23; 95% CI: 1.07
      4.63; p=0.03). Our results stress the need to control accelerated aging in this
      population to counter their increased risk of non-AIDS-defining diseases,
      particularly cancer, and are consistent with the concept that clinical
      complications are potentially affected by genetics and lifestyle. 

PMID- 25766862
TI  - Enzymatic synthesis of acyclic nucleoside thiophosphonate diphosphates: effect of
      the alpha-phosphorus configuration on HIV-1 RT activity.
AB  - The acyclic nucleosides thiophosphonates (9-[2
      (thiophosphonomethoxy)ethyl]adenine (S-PMEA) and (R)-9-[2
      (thiophosphonomethoxy)propyl]adenine (S-PMPA), exhibit antiviral activity against
      HIV-1, -2 and HBV. Their diphosphate forms S-PMEApp and S-PMPApp, synthesized as
      stereoisomeric mixture, are potent inhibitors of wild-type (WT) HIV-1 RT.
      Understanding HIV-1 RT stereoselectivity, however, awaits resolution of the
      diphosphate forms into defined stereoisomers. To this aim, thiophosphonate
      monophosphates S-PMEAp and S-PMPAp were synthesized and used in a
      stereocontrolled enzyme-catalyzed phosphoryl transfer reaction involving either
      nucleoside diphosphate kinase (NDPK) or creatine kinase (CK) to obtain
      thiophosphonate diphosphates as separated isomers. We then quantified substrate
      preference of recombinant WT HIV-1 RT toward pure stereoisomers using in vitro
      steady-state kinetic analyses. The crystal structure of a complex between
      Dictyostelium NDPK and S-PMPApp at 2.32A allowed to determine the absolute
      configuration at the alpha-phosphorus atom in relation to the stereo-preference
      of studied enzymes. The RP isomer of S-PMPApp and S-PMEApp are the preferred
      substrate over SP for both NDPK and HIV-1 RT. 

PMID- 25766863
TI  - Cost-effectiveness analysis of ferric carboxymaltose in iron-deficient patients
      with chronic heart failure in Sweden.
AB  - OBJECTIVE: Iron deficiency is a common but treatable comorbidity in chronic heart
      failure (CHF) that is associated with impaired health-related quality-of-life
      (HRQoL). This study evaluates the cost-effectiveness of the intravenous iron
      preparation ferric carboxymaltose (FCM) for the treatment of iron deficiency in
      CHF from a Swedish healthcare perspective. METHODS: A cost-effectiveness analysis
      with a time horizon of 24 weeks was performed to compare FCM treatment with
      placebo. Data on health outcomes and medical resource use were mainly taken from
      the FAIR-HF trial and combined with Swedish cost data. An incremental cost
      effectiveness ratio (ICER) was calculated as well as the change in per-patient
      costs for primary care and hospital care. RESULTS: In the FCM group compared with
      placebo, quality-adjusted life years (QALYs) are higher (difference = 0.037
      QALYs), but so are per-patient costs [(difference = SEK 2789 (?303)]. Primary
      care and hospital care equally share the additional costs, but within hospitals
      there is a major shift of costs from inpatient care to outpatient care. The ICER
      is SEK 75,389 (?8194) per QALY. The robustness of the result is supported by
      sensitivity analyses. CONCLUSIONS: Treatment of iron deficiency in CHF with FCM
      compared with placebo is estimated to be cost-effective. The ICER in the base
      case scenario is twice as high as previously thought, but noticeably below SEK
      500,000 (?54,300) per QALY, an informal average reference value used by the
      Swedish Dental and Pharmaceutical Benefits Agency. Increased HRQoL and fewer
      hospitalizations are the key drivers of this result.

PMID- 25766864
TI  - Prognostic factors for survival following initiation of second-line treatment
      with everolimus for metastatic renal cell carcinoma: evidence from a nationwide
      sample of clinical practice in the United States.
AB  - OBJECTIVE: Comparing prognostic factors for overall survival (OS) in community
      practice metastatic renal cell carcinoma (mRCC) patients receiving second-line
      everolimus with those previously reported in clinical trials. RESEARCH DESIGN AND
      METHODS: Two separate chart sets (2009 - 2012) were used to develop and validate
      a prognostic model for patients initiating second-line everolimus after first
      line tyrosine kinase inhibitor (TKI). MAIN OUTCOME MEASURES: Prognostic factors
      for OS have been identified and validated in separate samples. RESULTS: One-year
      OS probabilities in the study (n = 220) and validation (n = 97) samples were 68
      and 67%; median OS was 19 and 23 months - higher than the 1-year OS of 60% and
      median OS of 14.8 months of RECORD-1. Karnofsky performance score < 80%, duration
      of mRCC < 1 year, progression on first-line TKI, liver metastasis and clear cell
      histology were significant prognostic factors for shorter survival. One-year OS
      estimates were 84% for validation sample patients with 0 - 2 risk factors, 63%
      for 3 risk factors and 22% for 4 - 5 risk factors (log-rank p < 0.001).
      CONCLUSION: Real-world prognostic factors for OS following second-line everolimus
      for mRCC were largely consistent with those previously identified in trial data;
      however, OS was longer in the practice setting than in clinical trials and was
      not associated with type of first-line TKI.

PMID- 25766865
TI  - Hydroamination reactions of alkynes with ortho-substituted anilines in ball
      mills: synthesis of benzannulated N-heterocycles by a cascade reaction.
AB  - It was demonstrated that ortho-substituted anilines are prone to undergo
      hydroamination reactions with diethyl acetylenedicarboxylate in a planetary ball
      mill. A sequential coupling of the intermolecular hydroamination reaction with
      intramolecular ring closure was utilized for the syntheses of benzooxazines,
      quinoxalines, and benzothiazines from readily available building blocks, that is,
      electrophilic alkynes and anilines with OH, NH, or SH groups in the ortho
      position. For the heterocycle formation, it was shown that several stress
      conditions were able to initiate the reaction in the solid state. Processing in a
      ball mill seemed to be advantageous over comminution with mortar and pestle with
      respect to process control. In the latter case, significant postreaction
      modification occurred during solid-state analysis. Cryogenic milling proved to
      have an adverse effect on the molecular transformation of the reagents. 

PMID- 25766866
TI  - Increased cause-specific mortality in patients with mild and severe psoriasis: a
      population-based Swedish register study.
AB  - Several studies have shown excess risk for a number of comorbidities in patients
      with psoriasis compared with the general population, but data on cause-specific
      mortality in this patient population are limited. The aim of this study was to
      estimate the associations of psoriasis and 12 specific causes of death and all
      cause mortality in patients with mild and severe psoriasis. The study was based
      on data from Swedish administrative registers and compared the risk of death in
      39,074 patients with psoriasis with 154,775 sex-, age- and residency-matched
      referents using Cox proportional hazards models. In patients with mild and severe
      psoriasis, the strongest associations were observed for deaths due to kidney
      disease (hazard ratio [HR]=2.20, p < 0.01) and liver disease (HR = 4.26, p <
      0.001), respectively. Whilst cardiovascular disease was the main driver of excess
      mortality in absolute terms, the risks for other causes of death were also
      substantially elevated in patients with psoriasis compared with matched
      referents. 

PMID- 25766867
TI  - Neuroanatomical and morphological trait clusters in the ant genus Pheidole:
      evidence for modularity and integration in brain structure.
AB  - A central question in brain evolution concerns how selection has structured
      neuromorphological variation to generate adaptive behavior. In social insects,
      brain structures differ between reproductive and sterile castes, and worker
      behavioral specializations related to morphology, age, and ecology are associated
      with intra- and interspecific variation in investment in functionally different
      brain compartments. Workers in the hyperdiverse ant genus Pheidole are
      morphologically and behaviorally differentiated into minor and major subcastes
      that exhibit distinct species-typical patterns of brain compartment size
      variation. We examined integration and modularity in brain organization and its
      developmental patterning in three ecotypical Pheidole species by analyzing intra-
      and interspecific morphological and neuroanatomical covariation. Our results
      identified two trait clusters, the first involving olfaction and social
      information processing and the second composed of brain regions regulating
      nonolfactory sensorimotor functions. Patterns of size covariation between brain
      compartments within subcastes were consistent with levels of behavioral
      differentiation between minor and major workers. Globally, brains of mature
      workers were more heterogeneous than brains of newly eclosed workers, suggesting
      diversified developmental trajectories underscore species- and subcaste-typical
      brain organization. Variation in brain structure associated with the striking
      worker polyphenism in our sample of Pheidole appears to originate from initially
      differentiated brain templates that further diverge through species- and subcaste
      specific processes of maturation and behavioral development.

PMID- 25766868
TI  - Compound-specific stable carbon isotopic signature of carbohydrate pyrolysis
      products from C3 and C4 plants.
AB  - BACKGROUND: Pyrolysis-compound specific isotopic analysis (Py-CSIA: Py-GC-(FID)-C
      IRMS) is a relatively novel technique that allows on-line quantification of
      stable isotope proportions in chromatographically separated products released by
      pyrolysis. Validation of the Py-CSIA technique is compulsory for molecular
      traceability in basic and applied research. In this work, commercial sucrose from
      C4 (sugarcane) and C3 (sugarbeet) photosystem plants and admixtures were studied
      using analytical pyrolysis (Py-GC/MS), bulk delta(13)C IRMS and delta(13)C Py
      CSIA. RESULTS: Major pyrolysis compounds were furfural (F), furfural-5
      hydroxymethyl (HMF) and levoglucosan (LV). Bulk and main pyrolysis compound
      delta(13)C (0/00) values were dependent on plant origin: C3 (F, -24.65 +/- 0.89;
      HMF, -22.07 +/- 0.410/00; LV, -21.74 +/- 0.170/00) and C4 (F, -14.35 +/-
      0.890/00; HMF, -11.22 +/- 0.540/00; LV, -11.44 +/- 1.260/00). Significant
      regressions were obtained for delta(13)C of bulk and pyrolysis compounds in C3
      and C4 admixtures. Furfural (F) was found (13)C depleted with respect to bulk and
      HMF and LV, indicating the incorporation of the light carbon atom in position 6
      of carbohydrates in the furan ring after pyrolysis. CONCLUSION: This is the first
      detailed report on the delta(13)C signature of major pyrolytically generated
      carbohydrate-derived molecules. The information provided by Py-CSIA is valuable
      for identifying source marker compounds of use in food science/fraud detection or
      in environmental research.

PMID- 25766869
TI  - Manual assembly of nanocrystals for enhanced photoelectrochemical efficiency of
      hematite film.
AB  - To improve the optoelectronic properties of hematite film as a photoanode,
      hematite film was orientated on the (012) plane by the secondary growth of
      organized microcrystals. The resultant film showed promising photoelectrochemical
      effects compared with a randomly oriented one, with a maximum photocurrent of 0.8
      mA cm(-2) at 1.23 V vs. RHE under the illumination of 1 sun. 

PMID- 25766870
TI  - Magnetic properties in alpha-MnO2 doped with alkaline elements.
AB  - alpha-MnO2 nanotubes were fabricated using a hydrothermal technique. Li, Na and K
      ions were introduced into MnO2 nanotubes to tailor their magnetic properties. It
      was found that with a doping concentration lower than 12 at%, the nanotubes
      showed ferromagnetic-like ordering at low temperature (<50 K), while
      antiferromagnetic coupling dominated their physical behavior with doping
      concentrations beyond 12 at%. Such experimental phenomenon was in very good
      agreement with associated first principle calculations. The ferromagnetic-like
      ordering originates from the breaking of equivalence between two different Mn-O
      octahedrals in alpha-MnO2 due to the filling of alkaline ions in the tunnels.
      Both small charge transfer and lattice distortion play important roles in the
      ferromagnetic ordering.

PMID- 25766871
TI  - New insights into redox regulation of stem cell self-renewal and differentiation.
AB  - BACKGROUND: Reactive oxygen species (ROS), the natural byproducts of aerobic
      metabolism, are precisely orchestrated to evoke diverse signaling pathways. To
      date, studies have focused mainly on the detrimental effects of ROS in stem
      cells. Recently, accumulating evidence has suggested that ROS also function as
      second messengers that modulate stem cell self-renewal and differentiation by
      regulating intricate signaling networks. Although many efforts have been made to
      clarify the general effects of ROS on signal transduction in stem cells, less is
      known about the initial and direct executors of ROS signaling, which are known as
      'redox sensors'. SCOPE OF REVIEW: Modifications of cysteine residues in redox
      sensors are of significant importance in the modulation of protein function in
      response to different redox conditions. Intriguingly, most key molecules in ROS
      signaling and cell cycle regulation (including transcriptional factors and
      kinases) that are crucial in the regulation of stem cell self-renewal and
      differentiation have the potential to be redox sensors. MAJOR CONCLUSIONS: We
      highlight herein the importance of redox regulation of these key regulators in
      stem cell self-renewal and differentiation. GENERAL SIGNIFICANCE: Understanding
      the mechanisms of redox regulation in stem cell self-renewal and differentiation
      will open exciting new perspectives for stem cell biology. This article is part
      of a Special Issue entitled Redox regulation of differentiation and de
      differentiation.

PMID- 25766872
TI  - Pin1: Intimate involvement with the regulatory protein kinase networks in the
      global phosphorylation landscape.
AB  - BACKGROUND: Protein phosphorylation is a universal regulatory mechanism that
      involves an extensive network of protein kinases. The discovery of the
      phosphorylation-dependent peptidyl-prolyl isomerase Pin1 added an additional
      layer of complexity to these regulatory networks. SCOPE OF REVIEW: We have
      evaluated interactions between Pin1 and the regulatory kinome and proline
      dependent phosphoproteome taking into consideration findings from targeted
      studies as well as data that has emerged from systematic phosphoproteomic
      workflows and from curated protein interaction databases. MAJOR CONCLUSIONS: The
      relationship between Pin1 and the regulatory protein kinase networks is not
      restricted simply to the recognition of proteins that are substrates for proline
      directed kinases. In this respect, Pin1 itself is phosphorylated in cells by
      protein kinases that modulate its functional properties. Furthermore, the
      phosphorylation-dependent targets of Pin1 include a number of protein kinases as
      well as other enzymes such as phosphatases and regulatory subunits of kinases
      that modulate the actions of protein kinases. GENERAL SIGNIFICANCE: As a result
      of its interactions with numerous protein kinases and their substrates, as well
      as itself being a target for phosphorylation, Pin1 has an intricate relationship
      with the regulatory protein kinase and phosphoproteomic networks that orchestrate
      complex cellular processes and respond to environmental cues. This article is
      part of a Special Issue entitled Proline-directed Foldases: Cell Signaling
      Catalysts and Drug Targets.

PMID- 25766873
TI  - The role of His-83 of yeast apurinic/apyrimidinic endonuclease Apn1 in catalytic
      incision of abasic sites in DNA.
AB  - BACKGROUND: The apurinic/apyrimidinic (AP) endonuclease Apn1 from Saccharomyces
      cerevisiae is a key enzyme involved in the base excision repair (BER) at the
      cleavage stage of abasic sites (AP sites) in DNA. The crystal structure of Apn1
      from S. cerevisiae is unresolved. Based on its high amino acid homology to
      Escherichia coli Endo IV, His-83 is believed to coordinate one of three Zn2+ ions
      in Apn1's active site similar to His-69 in Endo IV. Substituting His-83 with Ala
      is proposed to decrease the AP endonuclease activity of Apn1 owing to weak
      coordination of Zn2+ ions involved in enzymatic catalysis. METHODS: The kinetics
      of recognition, binding, and incision of DNA substrates with the H83A Apn1 mutant
      was investigated. The stopped-flow method detecting fluorescence intensity
      changes of 2-aminopurine (2-aPu) was used to monitor the conformational dynamics
      of DNA at pre-steady-state conditions. RESULTS: We found substituting His-83 with
      Ala influenced catalytic complex formation and further incision of the damaged
      DNA strand. The H83A Apn1 catalysis depends not only on the location of the
      mismatch relative to the abasic site in DNA, but also on the nature of damage.
      CONCLUSIONS: We consider His-83 properly coordinates the active site Zn2+ ion
      playing a crucial role in catalytic incision stage. Our data prove suppressed
      enzymatic activity of H83A Apn1 results from the reduced number of active site
      Zn2+ ions. GENERAL SIGNIFICANCE: Our study provides insights into mechanistic
      specialty of AP site repair by yeast AP endonuclease Apn1 of Endo IV family,
      which members are not found in mammals, but are present in many microorganisms.
      The results will provide useful guidelines for design of new anti-fungal and anti
      malarial agents.

PMID- 25766874
TI  - Anthropometric and nutritional parameters in Egyptian children and adolescents
      with osteogenesis imperfecta.
AB  - BACKGROUND/AIMS: Patients with osteogenesis imperfecta (OI) present with various
      degrees of short stature and nutritional disorders. Thus, we aimed to evaluate
      anthropometric and nutritional parameters in OI children and their variability
      among various types. METHODS: Eighty-four patients with OI (types I, II, and IV)
      were subjected to the following anthropometric measurements: standing height
      (Ht), sitting height (SH), arm span, weight (Wt), and head circumference (HC),
      with calculation of Ht, SH, Wt, body mass index (BMI), and HC standard deviation
      scores (SDSs), and relative arm span. Triceps skinfold thickness (TSFT),
      subscapular skinfold thickness (SSFT), and mid upper arm circumference (MUAC)
      were measured, as well as dietary intake of macronutrients and calcium; also,
      energy requirements were calculated. RESULTS: Ht SDS was reduced in OI-III and OI
      IV compared to OI-I; SH SDS was reduced in OI-III compared to OI-I. HC SDS was
      more increased in OI-III than in OI-I and OI-IV. BMI SDS correlated with TSFT,
      SSFT, and MUAC. OI-III patients had the highest percentage of energy intake. The
      frequency of low macronutrient and calcium intake was highest in OI-III, while
      the frequency of low fat intake was highest in OI-I. CONCLUSIONS: Anthropometric
      and nutritional parameters differ among OI types. Assessment of anthropometric
      measurements and nutritional status in OI patients is important.

PMID- 25766875
TI  - Sumoylation controls the timing of Tup1-mediated transcriptional deactivation.
AB  - The small ubiquitin-like modifier (SUMO) is implicated in various cellular
      activities, including transcriptional regulation. We previously showed that the
      yeast activator Gcn4 becomes sumoylated during activation, facilitating its
      eventual promoter eviction and transcriptional shut off. Here we show that the
      corepressor Tup1 is sumoylated, at two specific lysines, under various stress
      conditions. Mutation of these sites has no effect on Tup1 recruitment or RNAP II
      promoter occupancy immediately following induction. However, Tup1 levels
      subsequently decrease, while RNAP II and transcription increase in Tup1 mutant
      cells. Consistent with this, a Tup1 mutant displaying increased sumoylation led
      to reduced transcription. We also show that coordinated sumoylation of Gcn4 and
      Tup1 enhances Gcn4 promoter eviction and that multiple Tup1-interacting proteins
      become sumoylated after stress. Together, our studies provide evidence that
      coordinated sumoylation of Gcn4, Tup1 and likely other factors dampens activated
      transcription by stabilizing Tup1 binding and stimulating Gcn4 and RNAP II
      removal. 

PMID- 25766877
TI  - Survey on specific nursing competences: Students' perceptions.
AB  - INTRODUCTION: The nursing profession requires sophisticated interdisciplinary
      knowledge and skills, which is why numerous nursing curricula are being developed
      all across the world. The aim of the study was to assess students' perspectives
      about competences, defined by the Tuning project, they acquired and developed
      since enrolment in the undergraduate nursing study programme. METHODS: A survey
      was performed amongst 69 postgraduate Master degree students at the Faculty of
      Health Sciences University of Maribor, Slovenia (nursing graduates) and the
      research results were analysed using conventional statistical and correspondence
      analysis. RESULTS: Most of the participants felt that they are more competent in
      their awareness of different roles, responsibilities and functions of a nurse
      together with the ability to practice within the context of professional,
      ethical, regulatory and legal codes. However they felt less competent in
      leadership, management, and team competences. CONCLUSIONS: According to the
      students' perceptions the current Nursing curriculum should be more future
      oriented and needs some core changes regarding the scope and level competences
      taught.

PMID- 25766876
TI  - Rat Cytomegalovirus Vaccine Prevents Accelerated Chronic Rejection in CMV-Naive
      Recipients of Infected Donor Allograft Hearts.
AB  - Cytomegalovirus accelerates transplant vascular sclerosis (TVS) and chronic
      rejection (CR) in solid organ transplants; however, the mechanisms involved are
      unclear. We determined the efficacy of a CMV vaccine in preventing CMV
      accelerated rat cardiac allograft rejection in naive recipients of CMV+ donor
      hearts. F344 donor rats were infected with RCMV 5 days prior to heterotopic
      cardiac transplantation into CMV-naive or H2 O2 -inactivated RCMV-vaccinated
      Lewis recipients. Recipients of RCMV-infected donor hearts rejected at POD59,
      whereas vaccinated recipients exhibited a significantly prolonged time to
      rejection-POD97, similar to recipients of uninfected donor hearts (POD108).
      Although all of the donor hearts were preinfected, the vaccinated recipients had
      lower graft and PBMC viral loads at POD 7 compared to unvaccinated controls.
      Adoptive T cell and passive antibody transfers from vaccinated Lewis rats into
      naive recipients demonstrate that both T-cell and B-cell arms of the adaptive
      immune response provide protection against CMV-accelerated rejection. Similar
      findings were obtained when testing three different adjuvants in passive transfer
      experiments. We have determined that the timing of the vaccine prior to
      transplantation and the specific adjuvant play critical roles in mediating anti
      viral responses and promoting graft survival. CMV vaccination prior to
      transplantation may effectively increase graft survival. 

PMID- 25766878
TI  - Molecular characterization, modeling and docking of CYP107CB2 from Bacillus
      lehensis G1, an alkaliphile.
AB  - Cytochrome P450s are a superfamily of heme monooxygenases which catalyze a wide
      range of biochemical reactions. The reactions involve the introduction of an
      oxygen atom into an inactivated carbon of a compound which is essential to
      produce an intermediate of a hydroxylated product. The diversity of chemical
      reactions catalyzed by cytochrome P450s has led to their increased demand in
      numerous industrial and biotechnology applications. A recent study showed that a
      gene sequence encoding a CYP was found in the genome of Bacillus lehensis G1, and
      this gene shared structural similarity with the bacterial vitamin D hydroxylase
      (Vdh) from Pseudonocardia autotrophica. The objectives of present study was to
      mine, for a novel CYP from a new isolate B. lehensis G1 alkaliphile and determine
      the biological properties and functionalities of CYP in this bacterium. Our study
      employed the usage of computational methods to search for the novel CYP from CYP
      structural databases to identify the conserved pattern, functional domain and
      sequence properties of the uncharacterized CYP from B. lehensis G1. A
      computational homology model of the protein's structure was generated and a
      docking analysis was performed to provide useful structural knowledge on the
      enzyme's possible substrate and their interaction. Sequence analysis indicated
      that the newly identified CYP, termed CYP107CB2, contained the fingerprint heme
      binding sequence motif FxxGxxxCxG at position 336-345 as well as other highly
      conserved motifs characteristic of cytochrome P450 proteins. Using docking
      studies, we identified Ser-79, Leu-81, Val-231, Val-279, Val-383, Ala-232, Thr
      236 and Thr-283 as important active site residues capable of stabilizing
      interactions with several potential substrates, including vitamin D3, 25
      hydroxyvitamin D3 and 1alpha-hydroxyvitamin D3, in which all substrates docked
      proximally to the enzyme's heme center. Biochemical analysis indicated that
      CYP107CB2 is a biologically active protein to produce 1alpha,25-dihydroxyvitamin
      D3 from 1alpha-hydroxyvitamin D3. Based on these results, we conclude that the
      novel CYP107CB2 identified from B. lehensis G1 is a putative vitamin D
      hydroxylase which is possibly capable of catalyzing the bioconversion of parental
      vitamin D3 to calcitriol, or related metabolic products. 

PMID- 25766879
TI  - Chirality sensing using Ag+-thiol coordination polymers.
AB  - We report here chirality sensing using achiral Ag(+)-thiol coordination polymers
      as the framework which becomes CD active upon interaction with chiral species,
      taking p-mercaptophenylboronic acid as a thiol ligand that bears a binding group
      for monosaccharides. 

PMID- 25766880
TI  - Study of surface damage on cell envelope assessed by AFM and flow cytometry of
      Lactobacillus plantarum exposed to ethanol and dehydration.
AB  - AIMS: In this work, we evaluated freeze-drying damage at the surface level of
      oenological strain Lactobacillus plantarum UNQLp155, as well as its ability to
      grow in a synthetic wine with and without pre-acclimation. METHODS AND RESULTS:
      Damage on cell surface was studied by flow cytometry, zeta potential and atomic
      force microscopy, and cell survival was analysed by plate count. Results showed
      that beside cells acclimated at lower ethanol concentration (6% v/v) became more
      susceptible to drying than nonacclimated ones, after rehydration they maintain
      their increased ability to grow in a synthetic wine. Acclimation at a higher
      ethanol concentration (10% v/v) produces several damages on the cell surface
      losing its ability to grow in a synthetic wine. CONCLUSIONS: In this work, we
      showed for the first time that sublethal alterations on bacterial surface induced
      by a pre-acclimation with a low ethanol concentration (6%), upon a freeze-drying
      process, result in a better bacterial adaptation to the stress conditions of wine
      like medium, as well as to the preservation process. SIGNIFICANCE AND IMPACT OF
      THE STUDY: Understanding the adaptation to ethanol of oenological strains and
      their effects on the preservation process has a strong impact on winemaking
      process and allows to define the most appropriate conditions to obtain malolactic
      starters cultures.

PMID- 25766881
TI  - Role of genetics in lung transplant complications.
AB  - There is increasing knowledge that patients can be predisposed to a certain
      disease by genetic variations in their DNA. Extensive genetic variation has been
      described in molecules involved in short- and long-term complications after lung
      transplantation (LTx), such as primary graft dysfunction (PGD), acute rejection,
      respiratory infection, chronic lung allograft dysfunction (CLAD), and mortality.
      Several of these studies could not be confirmed or were not reproduced in other
      cohorts. However, large multicenter prospective studies need to be performed to
      define the real clinical consequence and significance of genotyping the donor and
      receptor of a LTx. The current review presents an overview of genetic
      polymorphisms (SNP) investigating an association with different complications
      after LTx. Finally, the major drawbacks, clinical relevance, and future
      perspectives will be discussed. 

PMID- 25766882
TI  - [Considerations on the use of transcranial ultrasound in diagnosing brain death].

PMID- 25766883
TI  - Identification of drug targets related to the induction of ventricular
      tachyarrhythmia through a systems chemical biology approach.
AB  - Ventricular tachyarrhythmia (VT) is one of the most serious adverse drug
      reactions leading to death. The in vitro assessment of the interaction of lead
      compounds with HERG potassium channels, which is one of the primary known causes
      of VT induction, is an obligatory test during drug development. However,
      experimental and clinical data support the hypothesis that the inhibition of ion
      channels is not the only mechanism of VT induction. Therefore, the identification
      of other drug targets contributing to the induction of VT is crucial. We
      developed a systems chemical biology approach for searching for such targets.
      This approach involves the following steps: (1) creation of special sets of VT
      causing and non-VT-causing drugs, (2) statistical analysis of in silico predicted
      drug-target interaction profiles of studied drugs with 1738 human protein targets
      for the identification of potential VT-related targets, (3) gene ontology and
      pathway enrichment analysis of the revealed targets for the identification of
      biological processes underlying drug-induced VT etiology, (4) creation of a
      cardiomyocyte regulatory network (CRN) based on general and heart-specific
      signaling and regulatory pathways, and (5) simulation of changes in the behavior
      of the CRN caused by the inhibition of each node for the identification of
      potential VT-related targets. As a result, we revealed 312 potential VT-related
      targets and classified them into 3 confidence categories: high (36 proteins),
      medium (111 proteins), and low (165 proteins) classes. The most probable targets
      may serve as a basis for experimental confirmation and may be used for in vitro
      or in silico assessments of the relationships between drug candidates and drug
      induced VT, the understanding of contraindications of drug application and
      dangerous drug combinations.

PMID- 25766884
TI  - In vivo imaging of cell proliferation for a dynamic, whole body, analysis of
      undesired drug effects.
AB  - Noninvasive in vivo imaging offers a novel approach to preclinical studies
      opening the possibility of investigating biological events in the spatiotemporal
      dimension (eg, in any district of the body in time). Toxicological analysis may
      benefit from this novel approach through precise identification of the time and
      the target organs of toxicity manifestations, and assessment of the reversibility
      of toxic insults. The current limitation for routine application of this
      technology is the lack of appropriate surrogate markers for imaging toxicological
      events. Here, we demonstrate that in vivo imaging of a proliferation marker is
      capable of measuring the reduction of cell proliferation due to
      genotoxic/apoptotic agents, gamma rays or antineoplastic drugs, or the increased
      proliferation associated with the inflammatory and regenerative reactions
      occurring after a toxic insult. A number of tools are currently available for
      imaging proliferation in preclinical and clinical settings, however our data
      provide a novel way to translate the evidence of toxic effects obtained in
      preclinical animal studies, by the direct, noninvasive measure of dividing cells
      in humans.

PMID- 25766885
TI  - Morphine-Induced Constipation Develops With Increased Aquaporin-3 Expression in
      the Colon via Increased Serotonin Secretion.
AB  - Aquaporin-3 (AQP3) is a water channel that is predominantly expressed in the
      colon, where it plays a critical role in the regulation of fecal water content.
      This study investigated the role of AQP3 in the colon in morphine-induced
      constipation. AQP3 expression levels in the colon were analyzed after oral
      morphine administration to rats. The degree of constipation was analyzed after
      the combined administration of HgCl(2) (AQP3 inhibitor) or fluoxetine (5-HT
      reuptake transporter [SERT] inhibitor) and morphine. The mechanism by which
      morphine increased AQP3 expression was examined in HT-29 cells. AQP3 expression
      levels in rat colon were increased during morphine-induced constipation. The
      combination of HgCl(2) and morphine improved morphine-induced constipation.
      Treatment with morphine in HT-29 cells did not change AQP3 expression. However, 5
      HT treatment significantly increased the AQP3 expression level and the nuclear
      translocation of peroxisome proliferator-activated receptor gamma (PPARgamma) 1 h
      after treatment. Pretreatment with fluoxetine significantly suppressed these
      increases. Fluoxetine pretreatment suppressed the development of morphine-induced
      constipation and the associated increase in AQP3 expression in the colon. The
      results suggest that morphine increases the AQP3 expression level in the colon,
      which promotes water absorption from the luminal side to the vascular side and
      causes constipation. This study also showed that morphine-induced 5-HT secreted
      from the colon was taken into cells by SERT and activated PPARgamma, which
      subsequently increased AQP3 expression levels.

PMID- 25766886
TI  - The Food-Associated Ribotoxin Deoxynivalenol Modulates Inducible NO Synthase in
      Human Intestinal Cell Model.
AB  - The intestinal epithelium possesses active immune functions including the
      production of proinflammatory cytokines and antimicrobial molecules such as
      nitric oxide (NO). As observed with immune cells, the production of NO by the
      intestinal epithelium is mainly due to the expression of the inducible NO
      synthase (iNOS or NOS2). Epithelial immune functions could be affected by many
      factors including pathogenic microorganisms and food-associated toxins (bacterial
      and fungal). Among the various mycotoxins, deoxynivalenol (DON) is known to alter
      the systemic and intestinal immunity. However, little is known about the effect
      of DON on the production of NO by the intestinal epithelium. We studied the
      impact of DON on the intestinal expression of iNOS using the Caco-2 cell model.
      In line with its proinflammatory activity, we observed that DON dose-dependently
      up-regulates the expression of iNOS mRNA. Surprisingly, DON failed to increase
      the expression of iNOS protein. When testing the effects of DON on cytokine
      mediated induction of iNOS, we found that very low concentrations of DON (ie, 1
      uM) decrease the amount of iNOS protein but not of iNOS mRNA. We demonstrated
      that DON's effect on iNOS protein relies on its ability to activate signal
      pathways and to increase iNOS ubiquitinylation and degradation through the
      proteasome pathway. Taken together, our results demonstrate that although DON
      causes intestinal inflammation, it suppresses the ability of the gut epithelium
      to express iNOS and to produce NO, potentially explaining the increased
      susceptibility of animals to intestinal infection following exposure to low doses
      of DON. 

PMID- 25766887
TI  - Sample size calculations for the design of cluster randomized trials: A summary
      of methodology.
AB  - Cluster randomized trial designs are growing in popularity in, for example,
      cardiovascular medicine research and other clinical areas and parallel
      statistical developments concerned with the design and analysis of these trials
      have been stimulated. Nevertheless, reviews suggest that design issues associated
      with cluster randomized trials are often poorly appreciated and there remain
      inadequacies in, for example, describing how the trial size is determined and the
      associated results are presented. In this paper, our aim is to provide pragmatic
      guidance for researchers on the methods of calculating sample sizes. We focus
      attention on designs with the primary purpose of comparing two interventions with
      respect to continuous, binary, ordered categorical, incidence rate and time-to
      event outcome variables. Issues of aggregate and non-aggregate cluster trials,
      adjustment for variation in cluster size and the effect size are detailed. The
      problem of establishing the anticipated magnitude of between- and within-cluster
      variation to enable planning values of the intra-cluster correlation coefficient
      and the coefficient of variation are also described. Illustrative examples of
      calculations of trial sizes for each endpoint type are included. 

PMID- 25766888
TI  - Interactive effects of supplemental UV-B and temperature in European aspen
      seedlings: Implications for growth, leaf traits, phenolic defense and associated
      organisms.
AB  - Past studies reveal opposite effects of elevated UV-B and temperature on plant
      growth and concentrations of UV-B absorbing compounds, yet few studies have dealt
      with the combined and interactive effects of these two climate change factors on
      woody dioecious plants. We investigated the interactive effects of UV-B and
      temperature treatments on growth, leaf traits and phenolic concentrations in
      Populus tremula L. (European aspen) seedlings. We also considered the
      consequences of these effects on their associated organisms: herbivorous insects,
      rust pathogens, the presence of endophytic fungi and whether or not the responses
      differ between genders and genotypes. Supplemental temperature and UV-B were
      modulated to +2  degrees C and +30.77% above ambient conditions, respectively.
      Warming increased growth, photosynthesis and foliar nitrogen concentration but
      reduced leaf thickness and phenolic concentrations. On the other hand,
      supplemental UV-B increased total phenolic glycosides, mainly flavonols and
      phenolic acids, and partially counteracted the positive effects of warming on
      growth. Fast growing genotypes were less susceptible to the growth-reducing
      effect of combined UVB + T, less infected with rust disease and less prone to
      insect damage probably due to their higher salicylate and lower nitrogen
      concentrations. Under ambient temperature, the males of European aspen were
      taller and had bigger leaves than the females, while under elevated temperature,
      females grew bigger and, under UV-B, had more tremulacin than males. The multiple
      interactive effects of UV-B and temperature on growth, leaf traits and phenolic
      compounds, highlight the importance of multifactor experiments as a realistic
      predictor of plant responses to climate change.

PMID- 25766889
TI  - Anal sphincter trauma and anal incontinence in urogynecological patients.
AB  - OBJECTIVES: To determine the prevalence of evidence of residual obstetric anal
      sphincter injury, to evaluate its association with anal incontinence (AI) and to
      establish minimal diagnostic criteria for significant (residual) external anal
      sphincter (EAS) trauma. METHODS: This was a retrospective analysis of ultrasound
      volume datasets of 501 patients attending a tertiary urogynecological unit. All
      patients underwent a standardized interview including determination of St Mark's
      score for those presenting with AI. Tomographic ultrasound imaging (TUI) was used
      to evaluate the EAS and the internal anal sphincter (IAS). RESULTS: Among a total
      of 501 women, significant EAS and IAS defects were found in 88 and 59,
      respectively, and AI was reported by 69 (14%). Optimal prediction of AI was
      achieved using a model that included four abnormal slices of the EAS on TUI. IAS
      defects were found to be less likely to be associated with AI. In a multivariable
      model controlling for age and IAS trauma, the presence of at least four abnormal
      slices gave an 18-fold (95% CI, 9-36; P < 0.0001) increase in the likelihood of
      AI, compared with those with fewer than four abnormal slices. Using receiver
      operating characteristics curve statistics, this model yielded an area under the
      curve of 0.86 (95% CI, 0.80-0.92). CONCLUSIONS: Both AI and significant EAS
      trauma are common in patients attending urogynecological units, and are strongly
      associated with each other. Abnormalities of the IAS seem to be less important in
      predicting AI. Our data support the practice of using, as a minimal criterion,
      defects present in four of the six slices on TUI for the diagnosis of significant
      EAS trauma.

PMID- 25766890
TI  - Matrix metalloproteinase inhibition by heterotrimeric triple-helical Peptide
      transition state analogues.
AB  - Matrix metalloproteinases (MMPs) have been implicated in numerous pathologies. An
      overall lack of selectivity has rendered active-site-targeted MMP inhibitors
      problematic. The present study describes MMP inhibitors that function by binding
      both secondary binding sites (exosites) and the active site. Heterotrimeric
      triple-helical peptide transition-state analogue inhibitors (THPIs) were
      assembled utilizing click chemistry. Three different heterotrimers were
      constructed, allowing for the inhibitory phosphinate moiety to be present
      uniquely in the leading, middle, or trailing strand of the triple helix. All
      heterotrimeric constructs had sufficient thermally stability to warrant analysis
      as inhibitors. The heterotrimeric THPIs were effective against MMP-13 and MT1
      MMP, with Ki values spanning 100-400 nM. Unlike homotrimeric THPIs, the
      heterotrimeric THPIs offered complete selectivity between MT1-MMP and MMP-1.
      Exosite-based approaches such as this provide inhibitors with desired MMP
      selectivities. 

PMID- 25766891
TI  - Approaches to reducing radiation dose from radionuclide myocardial perfusion
      imaging.
AB  - Radionuclide myocardial perfusion imaging (MPI) plays a vital role in the
      evaluation and management of patients with coronary artery disease. However,
      because of a steep growth in MPI in the mid 2000s, concerns about inappropriate
      use of MPI and imaging-related radiation exposure increased. In response, the
      professional societies developed appropriate-use criteria for MPI.
      Simultaneously, novel technology, image-reconstruction software for traditional
      scanners, and dedicated cardiac scanners emerged and facilitated the performance
      of MPI with low-dose and ultra-low-dose radiotracers. This paper provides a
      practical approach to performing low-radiation-dose MPI using traditional and
      novel technologies. 

PMID- 25766892
TI  - Predictive Value of Early-Stage Uptake of 3'-Deoxy-3'-18F-Fluorothymidine in
      Cancer Cells Treated with Charged Particle Irradiation.
AB  - The aim of this study was to investigate whether 3'-deoxy-3'-(18)F
      fluorothymidine ((18)F-FLT) can monitor the early response of tumor cell
      proliferation to charged particle irradiation in vitro and in vivo. METHODS: In
      vitro, after 0.1, 0.5, 1, 5, and 10 Gy of proton or carbon ion irradiation, (18)F
      FLT cell uptake was examined at 24 h and cell proliferation ability was measured
      from days 1 to 4. In vivo, after 0.5, 1, and 5 Gy of proton or carbon ion
      irradiation, (18)F-FLT PET imaging was performed on tumor-bearing BALB/c nu/nu
      mice at 24 h and tumor growth was measured from days 1 to 7. Tumor-to-background
      ratios of standardized uptake values were calculated to assess the (18)F-FLT
      accumulation in tumors. Both cells and mice also received x-irradiation as a
      control. RESULTS: In vitro, (18)F-FLT cell uptake was significantly lower after 1
      Gy of proton irradiation (P < 0.05) and carbon ion irradiation (P < 0.05) and
      after 5 Gy of x-irradiation (P < 0.01), but cell proliferation ability at these
      doses did not show significant differences until day 3. In vivo, (18)F-FLT tumor
      uptake was significantly lower after 1 Gy of proton (P < 0.001) and carbon ion
      irradiation (P < 0.01) and after 5 Gy of x-irradiation (P < 0.001), but tumor
      growth did not significantly differ at these doses until day 4 after proton
      irradiation, day 3 after carbon ion irradiation, and day 5 after x-irradiation.
      CONCLUSION: The reduction in (18)F-FLT uptake after charged particle irradiation
      was more rapid than the change in tumor growth in vivo or the change in cell
      proliferation ability in vitro. Therefore, (18)F-FLT is a promising tracer for
      monitoring the early response of cancer to charged particle irradiation.

PMID- 25766893
TI  - Comprehensive radionuclide esophagogastrointestinal transit study: methodology,
      reference values, and initial clinical experience.
AB  - A radionuclide methodology and reference values have been developed for a single
      gastrointestinal transit study including esophageal transit, liquid and solid
      gastric emptying, and small- and large-bowel transit, using (111)In
      diethylenetriaminepentaacetic acid (DTPA) with the standardized (99m)Tc-labeled
      solid meal. METHODS: Eighteen healthy subjects and 18 patients were investigated.
      The esophageal transit study was performed with 3.7 MBq (0.1 mCi) of (111)In-DTPA
      in 15 mL of water. A liquid-only 30-min gastric-emptying study followed, with
      ingestion of 3.7 MBq (0.1 mCi) of (111)In-DTPA in 300 mL of water. Then, a
      simultaneous solid-liquid emptying study was acquired after ingestion of a solid
      (99m)Tc-sulfur colloid-labeled meal and 7.4 MBq (0.2 mCi) of (111)In-DTPA in 120
      mL of water. Images were acquired intermittently for 4 h. Additional (111)In
      images were acquired at 5 and 6 h to measure small-bowel transit, and at 24, 48,
      and 72 h for large-bowel transit. RESULTS: Reference values were determined for
      esophageal transit (transit time, percentage emptying at 10 s), liquid-only
      gastric emptying (emptying half-time), liquid and solid emptying in a dual-phase
      solid-liquid study (emptying half-time and percentage emptying at 1, 2, 3, and 4
      h), small-bowel transit index (percentage transit to ileocecal valve at 6 h), and
      colonic transit (geometric center and percentage colonic emptying) at 24, 48, and
      72 h. Results from the first 18 patients found abnormal transit in 72% (13/18);
      clinical management changed in 61% (11/18). CONCLUSION: We have developed a
      radionuclide methodology and derived reference values for a comprehensive
      gastrointestinal transit study using (111)In-DTPA with the standardized (99m)Tc
      labeled solid meal. Our initial clinical experience suggests clinical value.

PMID- 25766894
TI  - Clinical Usefulness of 18F-FDG PET/CT for the Detection of Infections of Unknown
      Origin in Patients Undergoing Maintenance Hemodialysis.
AB  - Patients with end-stage renal disease undergoing maintenance hemodialysis (MHD)
      are highly prone to infections. The potential clinical usefulness of (18)F-FDG
      PET/CT for the detection of infections of unknown origin in this patient
      population remains unclear. This study was designed to investigate this issue.
      METHODS: Between October 2011 and July 2014, a total of 104 adult MHD patients
      with sepsis underwent (18)F-FDG PET/CT for the detection of unknown infection
      foci. Follow-up was continued until October 2014. Positive (18)F-FDG PET/CT
      findings and mortality served as the main outcome measures. RESULTS: Of the 104
      study patients, 73 (70.2%) had positive (18)F-FDG PET/CT findings, and a total of
      95 major infection foci were identified. Eighteen patients (24.6%) had at least 2
      infection foci on (18)F-FDG PET/CT scans. Seven (53.8%) of the 13 patients with
      primary vascular access-related infections had concurrent metastatic foci. Twenty
      eight patients (26.9%) had their treatments modified by (18)F-FDG PET/CT results.
      Multivariate logistic regression analysis demonstrated that low hemoglobin and
      high C-reactive protein levels at diagnosis were the independent predictors of
      positive (18)F-FDG PET/CT results. Twenty-seven patients (26.0%) died during
      their hospital stay, and 24 of them had positive (18)F-FDG PET/CT findings (P =
      0.014). Positive (18)F-FDG PET/CT results were an independent predictor of
      mortality (hazard ratio, 3.896; 95% confidence interval, 1.039-14.613; P =
      0.044). CONCLUSION: Our results suggest that (18)F-FDG PET/CT may be clinically
      useful for detecting occult infection foci in end-stage renal disease patients
      undergoing MHD. In this population, positive (18)F-FDG PET/CT findings may lead
      to a significant change in clinical management and independently predict
      mortality.

PMID- 25766895
TI  - The role of exploratory investigational new drugs for translating
      radiopharmaceuticals into first-in-human studies.
AB  - The Food and Drug Administration has provided a mechanism to reduce time and
      resources expended on new pharmaceuticals, including radiopharmaceuticals, in
      order to identify the most promising agents for further development. The
      exploratory investigational new drug guidance describes early phase 1 exploratory
      approaches involving microdoses of potential drug candidates that are consistent
      with regulatory requirements while maintaining the safety needed for human
      subjects, allowing sponsors to move ahead more quickly with the development of
      new agents. 

PMID- 25766896
TI  - Will comprehensive assessment from esophagus to large bowel revive the momentum
      for radionuclide gastrointestinal transit studies?

PMID- 25766897
TI  - Shine-Through in PET/MR Imaging: Effects of the Magnetic Field on Positron Range
      and Subsequent Image Artifacts.
AB  - Simultaneous PET/MR imaging is an emerging hybrid modality for clinical and
      preclinical imaging. The static magnetic field of the MR imaging device affects
      the trajectory of the positrons emitted by the PET radioisotopes. This effect
      translates into an improvement of the spatial resolution in transaxial images.
      However, because of the elongation of the positron range distribution along the
      magnetic field, the axial resolution worsens and shine-through artifacts may
      appear. These artifacts can lead to misinterpretation and overstaging. The aim of
      this work was to study the relevance of this effect. METHODS: Measurements were
      performed in a 3-tesla PET/MR scanner. A 1-cm(2) piece of paper, soaked with a
      radioisotope and placed in air, was scanned, and the magnitude of the shine
      through was quantified from the PET images for various radioisotopes.
      Additionally, PET/MR and PET/CT images of the lungs and the larynx with trachea
      of a deceased swine were obtained after injecting a mixture of NiSO4 and (68)Ga
      to simulate hot tumor lesions. RESULTS: For the radioactive paper, shine-through
      artifacts appeared in the location of the acrylic glass backplane, located 3 cm
      from the source in the axial direction. The ratio between the activity of the
      shine-through and the activity reconstructed in the original location ranged from
      0.9 ((18)F) to 5.7 ((68)Ga). For the larynx-with-trachea images, the magnitude of
      the artifacts depended on the organ orientation with respect to the magnetic
      field. The shine-through activity could reach 46% of the reconstructed activity
      (larynx lesion). The lesion within the trachea produced 2 artifacts,
      symmetrically aligned with the magnetic field and characterized by artifact-to
      lesion volume-of-interest ratios ranging from 21% to 30%. CONCLUSION: In
      simultaneous PET/MR imaging, the effect of the magnetic field on positrons may
      cause severe artifacts in the PET image when the lesions are close to air
      cavities and high-energy radioisotopes are used. For accurate staging and
      interpretation, this effect needs to be recognized and adequate compensation
      techniques should be developed.

PMID- 25766898
TI  - Cerebellum Can Serve As a Pseudo-Reference Region in Alzheimer Disease to Detect
      Neuroinflammation Measured with PET Radioligand Binding to Translocator Protein.
AB  - Alzheimer disease (AD) is associated with an increase in the brain of the 18-kDa
      translocator protein (TSPO), which is overexpressed in activated microglia and
      reactive astrocytes. Measuring the density of TSPO with PET typically requires
      absolute quantitation with arterial blood sampling, because a reference region
      devoid of TSPO does not exist in the brain. We sought to determine whether a
      simple ratio method could substitute for absolute quantitation of binding with
      (11)C-PBR28, a second-generation radioligand for TSPO. METHODS: (11)C-PBR28 PET
      imaging was performed in 21 healthy controls, 11 individuals with mild cognitive
      impairment, and 25 AD patients. Group differences in (11)C-PBR28 binding were
      compared using 2 methods. The first was the gold standard method of calculating
      total distribution volume (V(T)), using the 2-tissue-compartment model with the
      arterial input function, corrected for plasma-free fraction of radiotracer
      (f(P)). The second method used a ratio of brain uptake in target regions to that
      in cerebellum-that is, standardized uptake value ratio (SUVR). RESULTS: Using
      absolute quantitation, we confirmed that TSPO binding (V(T)/f(P)) was greater in
      AD patients than in healthy controls in expected temporoparietal regions and was
      not significantly different among the 3 groups in the cerebellum. When the
      cerebellum was used as a pseudo-reference region, the SUVR method detected
      greater binding in AD patients than controls in the same regions as absolute
      quantification and in 1 additional region, suggesting SUVR may have greater
      sensitivity. Coefficients of variation of SUVR measurements were about two-thirds
      lower than those of absolute quantification, and the resulting statistical
      significance was much higher for SUVR when comparing AD and healthy controls
      (e.g., P < 0.0005 for SUVR vs. P = 0.023 for VT/fP in combined middle and
      inferior temporal cortex). CONCLUSION: To measure TSPO density in AD patients and
      control subjects, a simple ratio method SUVR can substitute for, and may even be
      more sensitive than, absolute quantitation. The SUVR method is expected to
      improve subject tolerability by allowing shorter scanning time and not requiring
      arterial catheterization. In addition, this ratio method allows smaller sample
      sizes for comparable statistical significance because of the relatively low
      variability of the ratio values.

PMID- 25766899
TI  - Standardization of administered activities in pediatric nuclear medicine: a
      report of the first nuclear medicine global initiative project, part 1-statement
      of the issue and a review of available resources.
AB  - The Nuclear Medicine Global Initiative (NMGI) was formed in 2012 and consists of
      13 international organizations with direct involvement in nuclear medicine. The
      underlying objectives of the NMGI were to promote human health by advancing the
      field of nuclear medicine and molecular imaging, encourage global collaboration
      in education, and harmonize procedure guidelines and other policies that
      ultimately lead to improvements in quality and safety in the field throughout the
      world. For its first project, the NMGI decided to consider the issues involved in
      the standardization of administered activities in pediatric nuclear medicine.
      This article presents part 1 of the final report of this initial project of the
      NMGI. It provides a review of the value of pediatric nuclear medicine, the
      current understanding of the carcinogenic risk of radiation as it pertains to the
      administration of radiopharmaceuticals in children, and the application of
      dosimetric models in children. A listing of pertinent educational and reference
      resources available in print and online is also provided. The forthcoming part 2
      report will discuss current standards for administered activities in children and
      adolescents that have been developed by various organizations and an evaluation
      of the current practice of pediatric nuclear medicine specifically with regard to
      administered activities as determined by an international survey of nuclear
      medicine clinics and centers. Lastly, the part 2 report will recommend a path
      forward toward global standardization of the administration of
      radiopharmaceuticals in children. 

PMID- 25766901
TI  - Strong second harmonic generation in SiC, ZnO, GaN two-dimensional hexagonal
      crystals from first-principles many-body calculations.
AB  - The second harmonic generation (SHG) intensity spectrum of SiC, ZnO, GaN two
      dimensional hexagonal crystals is calculated by using a real-time first
      principles approach based on Green's function theory [Attaccalite et al., Phys.
      Rev. B: Condens. Matter Mater. Phys. 2013 88, 235113]. This approach allows one
      to go beyond the independent particle description used in standard first
      principles nonlinear optics calculations by including quasiparticle corrections
      (by means of the GW approximation), crystal local field effects and excitonic
      effects. Our results show that the SHG spectra obtained using the latter approach
      differ significantly from their independent particle counterparts. In particular
      they show strong excitonic resonances at which the SHG intensity is about two
      times stronger than within the independent particle approximation. All the
      systems studied (whose stabilities have been predicted theoretically) are
      transparent and at the same time exhibit a remarkable SHG intensity in the range
      of frequencies at which Ti:sapphire and Nd:YAG lasers operate; thus they can be
      of interest for nanoscale nonlinear frequency conversion devices. Specifically
      the SHG intensity at 800 nm (1.55 eV) ranges from about 40-80 pm V(-1) in ZnO and
      GaN to 0.6 nm V(-1) in SiC. The latter value in particular is 1 order of
      magnitude larger than values in standard nonlinear crystals. 

PMID- 25766900
TI  - Late-responding normal tissue cells benefit from high-precision radiotherapy with
      prolonged fraction delivery times via enhanced autophagy.
AB  - High-precision radiotherapy (HPR) has established its important role in the
      treatment of tumors due to its precise dose distribution. Given its more
      complicated delivery process, HPR commonly requires more fraction delivery time
      (FDT). However, it is unknown whether it has an identical response of prolonged
      FDT on different normal tissues. Our results showed that fractionated irradiation
      with prolonged FDTs (15, 36, and 50 minutes) enhanced cell surviving fractions
      for normal tissue cells compared with irradiation with an FDT of 2 minutes.
      However, the late-responding normal cell line HEI-OC1 was more responsive to
      prolonged FDTs and demonstrated higher surviving fractions and significantly
      decreased apoptosis and DNA damage compared to the acute-responding normal cell
      line HaCaT. Increased autophagy mediated via the ATM-AMPK pathway was observed in
      HEI-OC1 cells compared with HaCaT cells when irradiated with prolonged FDTs.
      Furthermore, treatment with the autophagy inhibitor 3-MA or ATM inhibitor KU55933
      resulted in enhanced ROS accumulation and attenuation of the effect of prolonged
      FDT-mediated protection on irradiated HEI-OC1 cells. Our results indicated that
      late-responding normal tissue cells benefitted more from prolonged FDTs compared
      with acute-responding tissue cells, which was mainly attributed to enhanced
      cytoprotective autophagy mediated via the ATM/AMPK signaling pathway. 

PMID- 25766902
TI  - The Neandertals of northeastern Iberia: new remains from the Cova del Gegant
      (Sitges, Barcelona).
AB  - The present study describes a new juvenile hominin mandible and teeth and a new
      juvenile humerus from level V of the GP2 gallery of Cova del Gegant (Spain). The
      mandible (Gegant-5) preserves a portion of the right mandibular corpus from the
      M1 distally to the socket for the dc mesially, and the age at death is estimated
      as 4.5-5.0 years. Gegant-5 shows a single mental foramen located under the
      dm1/dm2 interdental septum, a relatively posterior placement compared with recent
      hominins of a similar developmental age. The mental foramen in Gegant-5 is also
      placed within the lower half of the mandibular corpus, as in the previously
      described late adolescent/adult mandible (Gegant-1) from this same Middle
      Paleolithic site. The Gegant-5 canine shows pronounced marginal ridges, a distal
      accessory ridge, and a pronounced distolingual tubercle. The P3 shows a lingually
      displaced protoconid cusp tip and a distal accessory ridge. The P4 shows a
      slightly asymmetrical crown outline, a continuous transverse crest, a mesially
      placed metaconid cusp tip, a slight distal accessory ridge, and an accessory
      lingual cusp. The M1 shows a Y5 pattern of cusp contact and a well-developed and
      deep anterior fovea bounded posteriorly by a continuous midtrigonid crest. Gegant
      4 is the distal portion of a left humerus from a juvenile estimated to be between
      5 and 7 years old at death. The specimen shows thick cortical bone. Although
      fragmentary, the constellation of morphological and metric features indicates
      Neandertal affinities for these specimens. Their spatial proximity at the site
      and similar ages at death suggest these remains may represent a single
      individual. The addition of these new specimens brings the total number of
      Neandertal remains from the Cova del Gegant to five, and this site documents the
      clearest evidence for Neandertal fossils associated with Middle Paleolithic stone
      tools in this region of the Iberian Peninsula. 

PMID- 25766903
TI  - Dioxin inhibition of swim bladder development in zebrafish: is it secondary to
      heart failure?
AB  - The swim bladder is a gas-filled organ that is used for regulating buoyancy and
      is essential for survival in most teleost species. In zebrafish, swim bladder
      development begins during embryogenesis and inflation occurs within 5 days post
      fertilization (dpf). Embryos exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin
      (TCDD) before 96 h post fertilization (hpf) developed swim bladders normally
      until the growth/elongation phase, at which point growth was arrested. It is
      known that TCDD exposure causes heart malformations that lead to heart failure in
      zebrafish larvae, and that blood circulation is a key factor in normal
      development of the swim bladder. The adverse effects of TCDD exposure on the
      heart occur during the same period of time that swim bladder development and
      growth occurs. Based on this coincident timing, and the dependence of swim
      bladder development on proper circulatory development, we hypothesized that the
      adverse effects of TCDD on swim bladder development were secondary to heart
      failure. We compared swim bladder development in TCDD-exposed embryos to: (1)
      silent heart morphants, which lack cardiac contractility, and (2) transiently
      transgenic cmlc2:caAHR-2AtRFP embryos, which mimic TCDD-induced heart failure via
      heart-specific, constitutive activation of AHR signaling. Both of these treatment
      groups, which were not exposed to TCDD, developed hypoplastic swim bladders of
      comparable size and morphology to those found in TCDD-exposed embryos.
      Furthermore, in all treatment groups swim bladder development was arrested during
      the growth/elongation phase. Together, these findings support a potential role
      for heart failure in the inhibition of swim bladder development caused by TCDD.

PMID- 25766904
TI  - ATML1 and PDF2 Play a Redundant and Essential Role in Arabidopsis Embryo
      Development.
AB  - The epidermis of shoot organs in plants develops from the outermost layer (L1) of
      the shoot apical meristem. In Arabidopsis, a pair of homeobox genes, ARABIDOPSIS
      THALIANA MERISTEM LAYER1 (ATML1) and PROTODERMAL FACTOR2 (PDF2), play a role in
      regulating the expression of L1-specific genes. atml1-1 pdf2-1 double mutants
      show striking defects in the differentiation of shoot epidermal cells. However,
      because atml1-1 and pdf2-1 have a T-DNA inserted downstream of the respective
      homeobox sequences, these alleles may not represent null mutations. Here we
      characterized additional mutant alleles that have a T-DNA insertion at different
      positions of each gene. Double mutants of a strong atml1-3 allele with each pdf2
      allele were found to cause embryonic arrest at the globular stage. Although with
      low frequency, all double mutant combinations of a weak atml1-1 allele with each
      pdf2 allele germinated and showed phenotypes defective in shoot epidermal cell
      differentiation. We further confirmed that transgenic induction of PDF2 fused to
      the Drosophila Engrailed repressor domain temporarily interferes with epidermal
      cell differentiation in the wild-type background. These results indicate that
      ATML1 and PDF2 act redundantly as a positive regulator of shoot epidermal cell
      differentiation and at least one copy of these genes is essential for embryo
      development. 

PMID- 25766905
TI  - A Brief History of Marchantia from Greece to Genomics.
AB  - While written accounts of plants date back thousands of years, due to the
      degradation of scientific literature during the dark ages descriptions descended
      from Greek writings are sometimes equivocal as to species identity. Such is the
      case with Marchantia in the pre-Renaissance literature; however, indisputable
      illustrations of Marchantia polymorpha were made as early as the mid-15th
      century, beginning a rich historical literature on its taxonomy, development and
      physiology. In this review, I present three vignettes, each of which are
      themselves abbreviated due to space constraints. The first presents the role of
      Marchantia and related liverwort species in the discovery of sex in cryptogams,
      from the elucidation of liverwort life cycles the 18th century to the sequence of
      the Y chromosome in the 21st. A second vignette describes the use of M.
      polymorpha as a model organism in the early 19th century debate concerning the
      cellular nature of organisms and the origin of new cells-an endeavor that
      provided us with Charles-Francois Brisseau de Mirbel's memoire containing
      beautiful, if slightly fanciful, illustrations of the Marchantia life cycle. The
      final vignette chronicles the use of M. polymorpha gemmae over the past two
      centuries to elucidate the mechanism by which a dorsiventral body plan is
      established from an initially apolar gemma. While only covering a fraction of the
      literature available, these vignettes provide a glimpse of historical and recent
      discoveries available upon which to build a molecular genetic and genomic
      understanding of Marchantia. 

PMID- 25766906
TI  - Role of theory of mind in emotional awareness and alexithymia: Implications for
      conceptualization and measurement.
AB  - The goal of this study was to determine whether alexithymia, which is
      characterized by difficulty in recognizing and describing emotions, is associated
      with impairments in the ability to mentally represent emotional states. We
      studied 89 outpatients including 29 conversion disorder patients, 30 functional
      somatic syndrome [e.g. fibromyalgia] patients and 30 medical controls. Groups did
      not differ on affective or cognitive Theory of Mind (ToM) measures, the Levels of
      Emotional Awareness Scale (LEAS) or the Twenty-Item Toronto Alexithymia Scale
      (TAS-20) after adjusting for Positive and Negative Affect Scale (PANAS)
      variables. Across all patients, LEAS but not TAS-20 correlated positively with
      affective and cognitive ToM measures after adjusting for PANAS scores.
      Impairments in ToM functioning influence LEAS performance but not TAS-20 scores.
      These findings support the distinction between a milder "anomia" form of
      alexithymia associated with impaired emotion naming and a more severe "agnosia"
      form associated with impaired mental representation of emotion. 

PMID- 25766907
TI  - Recent advances regarding constituents and bioactivities of plants from the genus
      Hypericum.

PMID- 25766908
TI  - From the sequence to the conformation of the unabridged transmembrane domains TM1
      and TM2 of the cASIC1a ion channel - a parallel tempering approach.
AB  - This work was devised to unravel, along replica-exchange molecular-dynamics
      (REMD) simulations, the conformation in solution of the TM1 and TM2 transmembrane
      domains of the homotrimeric cASIC1a ion channel. This includes the head of TM1
      and tail of TM2 that had previously defied X-ray diffraction analysis in the
      crystal. The structure of the open-channel complex of cASIC1a with psalmotoxin 1
      (PcTx1) was chosen here as a basis, although, to make the simulations affordable,
      the procedure was limited to the missing portions, including a few adjacent alpha
      helical turns. The latter were held fixed during the simulations. Reassembling
      the whole subunit, by superimposition of the fixed portions, resulted in diving
      of both TM1 and TM2 as continuous alpha-helices into the cytoplasm. At completion
      of this work, it appeared, from similar X-ray diffraction studies, that TM2 for
      both the complex of cASIC1a with the coral snake MitTx toxin, and the isolated
      desensitized ion channel, is discontinuous, with the triad G443-A444-S445 taking
      an extended, belt-like conformation. In this way, a filter ring against hydrated
      ions is formed by G443 in the trimer. Our REMD examination of this complex
      revealed a strong resistance by G443, and only that residue, to take dihedral
      angle values compatible with an alpha-helical conformation. This suggests that
      the flexibility of glycine alone does not explain formation of the extended, belt
      like conformation of the triad G443-A444-S445. This also requires cooperation in
      the trimer. 

PMID- 25766909
TI  - A new DNA-intercalative cytotoxic allylic xanthone from Swertia corymbosa.
AB  - Phytochemical investigation of the CHCl3 fraction of Swertia corymbosa resulted
      in the isolation of a new 3-allyl-2,8-dihydroxy-1,6-dimethoxy-9H-xanthen-9-one
      (1), along with four known xanthones, gentiacaulein (3), norswertianin (4),
      1,3,6,8-tetrahydroxyxanthone (5), and 1,3-dihydroxyxanthone (6). Structure of
      compound 1 was elucidated with the aid of IR, UV, NMR, and MS data, and chemical
      transformation via new allyloxy xanthone derivative (2). Compounds 1-6 exhibited
      various levels of antioxidant and anti-alpha-glucosidase activities. Absorption
      and fluorescence spectroscopic studies on 1-6 indicated that these compounds
      could interact with calf thymus DNA (CT-DNA) through intercalation and with
      bovine serum albumin (BSA) in a static quenching process. Compound 1 was found to
      be significantly cytotoxic against human cancer cell lines HeLa, HCT116, and AGS,
      and weakly active against normal NIH 3T3 cell line. 

PMID- 25766910
TI  - Drimane sesquiterpenoids from the Aspergillus oryzae QXPC-4.
AB  - Three new drimane sesquiterpenoids, astellolides C-E (1-3, resp.), four new
      drimane sesquiterpenoid p-hydroxybenzoates, astellolides F-I (4-7, resp.),
      together with two known compounds astellolides A and B (8 and 9, resp.), have
      been isolated from the liquid culture of Aspergillus oryzae (strain No. QXPC-4).
      Their structures were established by comprehensive analysis of spectroscopic
      data. The relative and absolute configurations were determined on the basis of
      NOESY and CD data, together with single-crystal X-ray diffraction analyses of
      compounds 1-3. The metabolites were evaluated for their cytotoxic activities,
      however, no compounds showed a significant cytotoxicity against the tested cell
      lines at a concentration of 20 MUM. 

PMID- 25766911
TI  - A comparative study on hulled adlay and unhulled adlay through evaluation of
      their LPS-induced anti-inflammatory effects, and isolation of pure compounds.
AB  - Coicis semen (=the hulled seed of Coix lacryma-jobi L. var. ma-yuen (Rom.Caill.)
      Stapf; Gramineae), commonly known as adlay and Job's tears, is widely used in
      traditional medicine and as a nutritious food. Bioassay-guided fractionation of
      the AcOEt fraction of unhulled adlays, using measurement of nitric oxide (NO)
      production on lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophage cells, led
      to the isolation and identification of two new stereoisomers, (+)
      (7'S,8'R,7"S,8"R)-guaiacylglycerol beta-O-4'-dihydrodisinapyl ether (1) and (+)
      (7'S,8'R,7"R,8"R)-guaiacylglycerol beta-O-4'-dihydrodisinapyl ether (2), together
      with six known compounds, 3-8. Compounds 3 and 4 exhibited inhibitory activities
      on LPS-induced NO production with IC50 values of 1.4 and 3.7 MUM, respectively,
      and suppressed inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX
      2) protein expressions in RAW 264.7 macrophage cells. Simple high-performance
      liquid chromatography with ultraviolet detection (HPLC/UV) was used to compare
      the AcOEt fraction of unhulled adlays responsible for the anti-inflammatory
      activity in RAW 264.7 cells and the inactive AcOEt fraction of hulled adlays. 

PMID- 25766912
TI  - Terpenoids from rhizomes of Alpinia japonica inhibiting nitric oxide production.
AB  - A new sesquiterpenoid, 1, and three new diterpenoids, 3-5, along with five known
      compounds, 2 and 6-9, were isolated from rhizomes of Alpinia japonica. The
      structures of the new compounds were determined as (1R,4R,6S,7S,9S)-4alpha
      hydroxy-1,9-peroxybisabola-2,10-diene (1), methyl (12E)-16-oxolabda-8(17),12-dien
      15-oate (3), (12R)-15-ethoxy-12-hydroxylabda-8(17),13(14)-dien-16,15-olide (4),
      and methyl (11E)-14,15,16-trinorlabda-8(17),11-dien-13-oate (5) by means of
      spectroscopic data. The absolute configurations at C(4) in 1 and C(12) in 4 were
      deduced from the circular dichroism (CD) data of the in situ-formed [Rh2 (CF3
      COO)4 ] complexes. Inhibitory effects of the isolates on NO production in
      lipopolysaccharide-induced RAW264.7 macrophages were evaluated, and 2-4, 6, and 7
      were found to exhibit inhibitory activities with IC50 values between 14.6 and
      34.3 MUM. 

PMID- 25766913
TI  - Content of fatty acids and phenolics in Coratina olive oil from Tunisia:
      influence of irrigation and ripening.
AB  - The quality indices and chemical composition of Coratina olive oil produced in
      the northern region of Tunisia were evaluated, to determine the effect of three
      different irrigation regimes of the trees on the olive oils. The olives were
      sampled at two different stages of maturity, the oils were extracted, and
      standard methods were used to analyze the composition and quality of the oils.
      The fatty-acid contents and quality parameters were only slightly affected by the
      irrigation regime. The contents of palmitic, oleic, and linoleic acids were above
      12, 72, and 8%, respectively, for the second harvest, regardless of the
      irrigation level of the olive trees. Parameters such as the alpha-tocopherol
      content and the phenolic profile were found to be significantly affected by the
      harvesting time; however, inconsistent changes were observed for the irrigation
      regimes, especially for the oil of the second harvest. It was shown that the
      irrigation conditions of the olive trees as well as the harvesting time of the
      fruits gave rise to a diverse range of olive oils in Tunisia. 

PMID- 25766914
TI  - Chemical composition and biological activity of Abies alba and A. koreana seed
      and cone essential oils and characterization of their seed hydrolates.
AB  - The chemical composition, including the enantiomeric excess of the main terpenes,
      the antimicrobial and antiradical activities, as well as the cytotoxicity of
      Abies alba and A. koreana seed and cone essential oils were investigated.
      Additionally, their seed hydrolates were characterized. In the examined oils and
      hydrolates, a total of 174 compounds were identified, which comprised 95.6-99.9%
      of the volatiles. The essential oils were mainly composed of monoterpene
      hydrocarbons, whereas the composition of the hydrolates, differing from the seed
      oils of the corresponding fir species, consisted mainly of oxygenated derivatives
      of sesquiterpenes. The seed and cone essential oils of both firs exhibited DPPH
      radical-scavenging properties and low antibacterial activity against the
      bacterial strains tested. Moreover, they evoked only low cytotoxicity towards
      normal fibroblasts and the two cancer cell lines MCF-7 and MDA-MBA-231. At
      concentrations up to 50 MUg/ml, all essential oils were safe in relation to
      normal fibroblasts. Although they induced cytotoxicity towards the cancer cells
      at concentrations slightly lower than those required for the inhibition of
      fibroblast proliferation, their influence on cancer cells was weak, with IC50
      values similar to those observed towards normal fibroblasts. 

PMID- 25766915
TI  - Biochemical characterization of Helichrysum italicum (Roth) G.Don subsp. italicum
      (Asteraceae) from Montenegro: phytochemical screening, chemotaxonomy, and
      antioxidant properties.
AB  - The chemical composition and antioxidant properties of the essential oil and EtOH
      extract of immortelle (Helichrysum italicum (Roth) G.Don subsp. italicum,
      Asteraceae) collected in Montenegro were evaluated. The essential oil was
      characterized by GC/MS analysis, and the content of total phenolics and
      flavonoids in the EtOH extract was determined using the Folin?Ciocalteu reagent.
      The free-radical-scavenging capacity (RSC) of both the essential oil and the EtOH
      extract was assessed with the 2,2-diphenyl-1-pycrylhydrazyl (DPPH) method.
      Moreover, the inhibition of hydroxyl radical ((.) OH) generation by the EtOH
      extract of immortelle was evaluated for the first time here. Neryl acetate
      (28.2%) and gamma-curcumene (18.8%) were the main compounds in the essential oil,
      followed by neryl propionate (9.1%) and ar-curcumene (8.3%). The chemical
      composition of the oils of the examined and additional 16 selected Helichrysum
      italicum taxa described in literature were compared using principal component
      (PCA) and cluster (CA) analyses. The results of the statistical analyses implied
      the occurrence of at least four different main and three subchemotypes of
      essential oils. Considering the antioxidant properties, the EtOH extract of
      immortelle exhibited similar potential as propyl gallate and quercetin, while the
      essential oil exhibited relatively weak DPPH(.) -scavenging capacity.

PMID- 25766916
TI  - Bioprospection of cytotoxic compounds in fungal strains recovered from sediments
      of the Brazilian coast.
AB  - The cytotoxic activities of extracts (50 MUg/ml) from 48 fungal strains,
      recovered from sediments of Pecem's offshore port terminal (Northeast coast of
      Brazil), against HCT-116 colon cancer cell lines were investigated. The most
      promising extract was obtained from strain BRF082, identified as Dichotomomyces
      cejpii by phylogenetic analyses of partial RPB2 gene sequence. Thus, it was
      selected for bioassay-guided isolation of the cytotoxic compounds. Large-scale
      fermentation of BRF082 in potato dextrose broth, followed by chromatographic
      purification of the bioactive fractions from the liquid medium, yielded gliotoxin
      (4) and its derivatives acetylgliotoxin G (3),
      bis(dethio)bis(methylsulfanyl)gliotoxin (1), acetylgliotoxin (5), 6
      acetylbis(dethio)bis(methylsulfanyl)gliotoxin (2), besides the quinazolinone
      alkaloid fiscalin B. All isolated compounds were tested for their cytotoxicities
      against the tumor cell lines HCT-116, revealing 4 and 3 as the most cytotoxic
      ones (IC50 0.41 and 1.06 MUg/ml, resp.). 

PMID- 25766917
TI  - Bioactive diphenyl ether derivatives from a gorgonian-derived fungus Talaromyces
      sp.
AB  - Three new diphenyl ether derivatives, talaromycins A-C (1-3, resp.), together
      with six known analogs, 4-9, were isolated from a gorgonian-derived fungus,
      Talaromyces sp. The structures of the new compounds were determined by analysis
      of extensive NMR spectroscopic data. All of the isolated metabolites, 1-9, were
      evaluated for their cytotoxic and antifouling activities. Compound 4 exhibited
      pronounced cytotoxicity against the tested human cell lines with the IC50 values
      ranging from 4.3 to 9.8 MUM. Compounds 3, 5, 8, and 9 showed potent antifouling
      activities against the larval settlement of the barnacle Balanus amphitrite with
      the EC50 values ranging from 2.2 to 4.8 MUg/ml. 

PMID- 25766918
TI  - Role of fluorine 18 fluorodeoxyglucose positron emission tomography/computed
      tomography in gastrointestinal cancers.
AB  - Fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography
      (FDG-PET/CT) has become a routine imaging modality for many malignancies and its
      use is currently increasing. In the present review article, we will summarize the
      evidence for FDG-PET/CT use in digestive cancers (excluding neuroendocrine
      tumours), and review the existing recommendations. While PET/CT is nowadays
      considered to be an important tool in the initial workup of oesophageal and anal
      cancers, new data are emerging regarding its use in assessing therapeutic
      efficacy, radiotherapy treatment planning, and detection of recurrence in case of
      isolated tumour marker elevation. Moreover, PET/CT may help decision making by
      detecting distant metastatic sites especially in potentially resectable
      metastatic colorectal cancer and, to a lesser extent, in localized gastric and
      pancreatic cancers. Finally, incidental focal colonic FDG uptakes require
      exploration by colonoscopy, as they are often associated with premalignant or
      malignant lesions. 

PMID- 25766919
TI  - Pneumoperitoneum due to cat scratch colon. Is it really such an innocent disease?

PMID- 25766920
TI  - A near-infrared two-photon-sensitive peptide-mediated liposomal delivery system.
AB  - Tumour-oriented nanocarrier drug delivery approaches with photo-sensitivity have
      been drawing considerable attention over the years. However, due to its low
      penetrability and ability to induce tissue damage, the use of UV light for
      triggered nanocarrier release in in vivo applications has been limited. Compared
      with UV light, near-infrared (NIR) light deeply penetrates tissues and is less
      damaging to cells. Here, we report on the development of a novel method employing
      photo-sensitive cell-penetrating peptides (CPPs), which can be used to trigger
      the transport of liposomes into cells following stimulation, which was
      irradiation with NIR light in this case. The positive charges of the lysine
      residues on the CPP were temporarily caged by a NIR two-photon excitation
      responsive protective group (PG), thereby forming photo-sensitive peptides
      (PSPs). The PSP was connected with DSPE via a polyethylene glycol (PEG) spacer to
      prepare the modified liposomes (PSP-L). Once illuminated by NIR light in tumour
      tissues, these PGs were cleaved, and the positively charged CPP regained its
      activity and facilitated rapid intracellular delivery of the liposomes into
      cancer cells. The PSP-L carrying vinorelbine bitartrate prepared in this work
      possessed suitable physiochemical properties. In addition, strong cellular uptake
      and cytotoxic activity of PSP-L in MCF-7 cells were correlated with NIR
      illumination. Furthermore, triggered NIR activation of PSP-L led to higher
      antitumour efficacy in the MCF-7 tumour model in nude mice compared with the
      unmodified liposomes (N-L). In conclusion, the application of PSP modifications
      to drug-carrying liposomes may provide an approach for the targeted delivery of
      antitumour agents. 

PMID- 25766921
TI  - Rod shaped nanocrystals exhibit superior in vitro dissolution and in vivo
      bioavailability over spherical like nanocrystals: a case study of lovastatin.
AB  - The objective of this study was to compare the in vitro and in vivo performance
      of rod shaped and spherical like nanocrystals for oral administration. Lovastatin
      (LOV) was chosen as the model drug and LOV rod shaped nanocrystals (LOV-RNs) and
      spherical like nanocrystals (LOV-SNs) were prepared by sonoprecipitation and bead
      milling, respectively. The dry powders obtained following freeze-drying were
      characterized by hydrodynamic diameter, polydispersity index, zeta potential,
      transmission electron microscope, scanning electron microscope, atomic force
      microscope, differential scanning calorimetry, Fourier transform infrared
      spectroscopy, and in vitro dissolution test. The pharmacokinetic study was
      performed in beagle dogs. The results obtained showed that LOV-RNs and LOV-SNs
      had similar hydrodynamic diameters (500.6+/-21.0 nm versus 503.2+/-20.4 nm), and
      the same crystalline state. The dissolution test showed that LOV-RNs had a higher
      dissolution rate than LOV-SNs. The AUC(0-24h) values of LOV-RNs and LOV-SNs were
      higher than Junning(r) for both LOV (p<0.05 for LOV-RNs, and p>0.05 for LOV-SNs)
      and lovastatin acid (p>0.05). More importantly, the oral bioavailability of LOV
      RNs was higher than LOV-SNs (p>0.05). The findings of this study show that the
      crystal shape has a significant effect on oral bioavailability.

PMID- 25766922
TI  - Nanoformulation of poly(ethylene glycol) polymerized organic insect repellent by
      PIT emulsification method and its application for Japanese encephalitis vector
      control.
AB  - The utilization of increased dosage of insect repellents to overcome mosquito
      resistance has raised environmental concerns globally. In accord to this, we have
      formulated an efficacious, water-dispersive, nanometric formulation of a poor
      water-soluble insect repellent, diethylphenylacetamide (DEPA) by poly(ethylene
      glycol) (PEG) polymerization followed by PIT emulsification method. The critical
      micelle concentration of PEG in the spontaneously emulsified conventional DEPA
      droplets was determined, based on the droplets physical stability. Subjecting
      them to PIT emulsification yielded monodispersed polymeric nanomicelles of DEPA
      (Nano DEPA) with hydrodynamic mean diameter of 153.74 nm. The high-resolution
      scanning and transmission electron microscopic studies revealed the
      characteristic core-shell structure of micelle. The comparative efficacy of Bulk
      DEPA and Nano DEPA was evaluated by larvicidal and WHO cone bioassay against the
      Japanese encephalitis vector Culex tritaeniorhynchus. The median lethal
      concentrations (48 h) for 3rd instars C. tritaeniorhynchus larvae were found to
      be 0.416 mg/L for Bulk DEPA and 0.052 mg/L for Nano DEPA, respectively. The
      median knockdown concentrations (60 min) for the two to three-day-old, sucrose
      fed, female adult mosquitoes were 5.372% (v/v) and 3.471% (v/v) for Bulk and Nano
      DEPA, respectively. Further investigation by histopathological and biochemical
      studies propound that Nano DEPA exerted better bioefficacy as comparative to its
      bulk form even at minimal exposure concentrations. Hence, Nano DEPA will serve as
      an effective alternate in controlling the vector expansion with reduced dosage.

PMID- 25766923
TI  - Formulation of resveratrol entrapped niosomes for topical use.
AB  - A new approach to the formulation of resveratrol (RSV) entrapped niosomes for
      topical use is proposed in this work. Niosomes were formulated with Gelot 64
      (G64) as surfactant, and two skin-compatible unsaturated fatty acids (oleic and
      linoleic acids), commonly used in pharmaceutical formulations, as penetration
      enhancers. Niosomes were prepared by two different methods: a thin film hydration
      method with minor modifications followed by a sonication stage (TFH-S), and an
      ethanol injection modified method (EIM). Niosomes prepared with the EIM method
      were in the range of 299-402 nm, while the TFH-S method produced larger niosomes
      in the range of 293-496 nm. Moreover, niosomes with higher RSV entrapment
      efficiency (EE) and better stability were generated by the EIM method. Ex vivo
      transdermal experiments, carried out in Franz diffusion cells on newborn pig
      skin, indicated that niosomes prepared by the EIM method were more effective for
      RSV penetration in epidermis and dermis (EDD), with values up to 21% for both
      penetration enhancers tested. The EIM method, which yielded the best RSV
      entrapped niosomes, seems to be the most suitable for scaling up.

PMID- 25766924
TI  - Nanostructures of an amphiphilic zinc phthalocyanine polymer conjugate for
      photodynamic therapy of psoriasis.
AB  - Psoriasis is a chronic inflammatory skin disease affecting 2-5% of the population
      worldwide and it severely affects patient quality of life. In this study, an
      amphiphilic zinc phthalocyanine polymer conjugate (ZPB) was synthesized, in which
      zinc phthalocyanine (ZnPc) was conjugated with the poly(ethylene glycol) (PEG)
      chain of Brij 58. ZPB showed two maximum UV-vis absorption wavelengths, 348 nm
      and 678 nm. A monomolecular micelle of ZPB formed in water with a mean size of 25
      nm and zeta potential of -15 mV. The nanostructures aggregated into cloudy
      precipitates, which were easily dispersed. The nanostructure showed the shell
      core structure with the ZnPc segments as the core and the PEG chains as the
      shell. The anti-psoriasis effect of the ZPB nanostructure was explored using a
      guinea pig psoriasis model. After comparing the anti-psoriasis effects of saline,
      light alone, ZPB alone, and the combination of light and ZPB, the combination of
      light and ZPB showed the best photodynamic therapy of psoriasis based on the
      light excitation of the photosensitizer ZPB and the psoriasis was nearly cured
      according to the histopathological investigation. The ZPB nanostructure is a
      promising anti-psoriasis nanomedicine based on photodynamic therapy.

PMID- 25766925
TI  - Higher order microfibre modes for dielectric particle trapping and propulsion.
AB  - Optical manipulation in the vicinity of optical micro- and nanofibres has shown
      potential across several fields in recent years, including microparticle control,
      and cold atom probing and trapping. To date, most work has focussed on the
      propagation of the fundamental mode through the fibre. However, along the maximum
      mode intensity axis, higher order modes have a longer evanescent field extension
      and larger field amplitude at the fibre waist compared to the fundamental mode,
      opening up new possibilities for optical manipulation and particle trapping. We
      demonstrate a microfibre/optical tweezers compact system for trapping and
      propelling dielectric particles based on the excitation of the first group of
      higher order modes at the fibre waist. Speed enhancement of polystyrene particle
      propulsion was observed for the higher order modes compared to the fundamental
      mode for particles ranging from 1 MUm to 5 MUm in diameter. The optical
      propelling velocity of a single, 3 MUm polystyrene particle was found to be 8
      times faster under the higher order mode than the fundamental mode field for a
      waist power of 25 mW. Experimental data are supported by theoretical
      calculations. This work can be extended to trapping and manipulation of laser
      cooled atoms with potential for quantum networks.

PMID- 25766926
TI  - Quantification of serum apolipoproteins A-I and B-100 in clinical samples using
      an automated SISCAPA-MALDI-TOF-MS workflow.
AB  - A fully automated workflow was developed and validated for simultaneous
      quantification of the cardiovascular disease risk markers apolipoproteins A-I
      (apoA-I) and B-100 (apoB-100) in clinical sera. By coupling of stable-isotope
      standards and capture by anti-peptide antibodies (SISCAPA) for enrichment of
      proteotypic peptides from serum digests to matrix-assisted laser
      desorption/ionization time-of-flight (MALDI-TOF) MS detection, the standardized
      platform enabled rapid, liquid chromatography-free quantification at a relatively
      high throughput of 96 samples in 12h. The average imprecision in normo- and
      triglyceridemic serum pools was 3.8% for apoA-I and 4.2% for apoB-100 (4
      replicates over 5 days). If stored properly, the MALDI target containing enriched
      apoA-1 and apoB-100 peptides could be re-analyzed without any effect on bias or
      imprecision for at least 7 days after initial analysis. Validation of the
      workflow revealed excellent linearity for daily calibration with external, serum
      based calibrators (R(2) of 0.984 for apoA-I and 0.976 for apoB-100 as average
      over five days), and absence of matrix effects or interference from
      triglycerides, protein content, hemolysates, or bilirubins. Quantification of
      apoA-I in 93 normo- and hypertriglyceridemic clinical sera showed good agreement
      with immunoturbidimetric analysis (slope = 1.01, R(2) = 0.95, mean bias = 4.0%).
      Measurement of apoB-100 in the same clinical sera using both methods, however,
      revealed several outliers in SISCAPA-MALDI-TOF-MS measurements, possibly as a
      result of the lower MALDI-TOF-MS signal intensity (slope = 1.09, R(2) = 0.91,
      mean bias = 2.0%). The combination of analytical performance, rapid cycle time
      and automation potential validate the SISCAPA-MALDI-TOF-MS platform as a valuable
      approach for standardized and high-throughput quantification of apoA-I and apoB
      100 in large sample cohorts.

PMID- 25766927
TI  - Methods of isolating extracellular vesicles impact down-stream analyses of their
      cargoes.
AB  - Viable tumor cells actively release vesicles into the peripheral circulation and
      other biologic fluids, which exhibit proteins and RNAs characteristic of that
      cell. Our group demonstrated the presence of these extracellular vesicles of
      tumor origin within the peripheral circulation of cancer patients and proposed
      their utility for diagnosing the presence of tumors and monitoring their response
      to therapy in the 1970s. However, it has only been in the past 10 years that
      these vesicles have garnered interest based on the recognition that they serve as
      essential vehicles for intercellular communication, are key determinants of the
      immunosuppressive microenvironment observed in cancer and provide stability to
      tumor-derived components that can serve as diagnostic biomarkers. To date, the
      clinical utility of extracellular vesicles has been hampered by issues with
      nomenclature and methods of isolation. The term "exosomes" was introduced in 1981
      to denote any nanometer-sized vesicles released outside the cell and to
      differentiate them from intracellular vesicles. Based on this original
      definition, we use "exosomes" as synonymous with "extracellular vesicles." While
      our original studies used ultracentrifugation to isolate these vesicles, we
      immediately became aware of the significant impact of the isolation method on the
      number, type, content and integrity of the vesicles isolated. In this review, we
      discuss and compare the most commonly utilized methods for purifying exosomes for
      post-isolation analyses. The exosomes derived from these approaches have been
      assessed for quantity and quality of specific RNA populations and specific marker
      proteins. These results suggest that, while each method purifies exosomal
      material, there are pros and cons of each and there are critical issues linked
      with centrifugation-based methods, including co-isolation of non-exosomal
      materials, damage to the vesicle's membrane structure and non-standardized
      parameters leading to qualitative and quantitative variability. The down-stream
      analyses of these resulting varying exosomes can yield misleading results and
      conclusions.

PMID- 25766928
TI  - Chemistry of lipid peroxidation products and their use as biomarkers in early
      detection of diseases.
AB  - We developed a novel method to measure hydroxyoctadecadienoic acid (HODE) levels
      in biological fluids and tissue samples. This method can be used to measure the
      oxidation products of linoleic acid. Reduction and saponification enabled us to
      measure hydroperoxides and hydroxides of both free and esterified forms of
      linoleic acid as total HODE, which includes the enzymatic and non-enzymatic
      products 9- and 13-(Z, E)-HODEs; the non-enzymatic free radical-mediated products
      9- and 13-(E, E)-HODEs; and the specific non-enzymatic singlet oxygen-mediated
      products 10- and 12-(Z, E)-HODEs. We have recently reported HODE levels in plasma
      and erythrocytes from healthy volunteers and patients with several diseases and
      determined that its levels are much higher in patients with lifestyle-related
      diseases than in healthy volunteers. Furthermore, 10- and 12-(Z, E)-HODE plasma
      levels can serve as promising biomarkers for the early detection of diabetes.
      Thus, HODE is a useful biomarker for the assessment of oxidative status, and its
      efficiency as a biomarker can be improved by using it in combination with other
      typical biomarkers. This review article focuses on lipid peroxidation biomarkers,
      including HODE, and discusses their potential in practical and clinical
      applications in disease prediction. 

PMID- 25766929
TI  - Factors affecting the phase behavior and antimicrobial activity of carvacrol
      microemulsions.
AB  - The aim of this study was to investigate some factors that can contribute to the
      formulation of aqueous-based carvacrol microemulsion that can potentially be used
      in food preservation or disinfection. For this purpose the capacity of formation
      of carvacrol microemulsion was first revealed by studying the phase behavior of
      that compound in five different non-ionic microemulsion systems. Factors
      affecting that phase behavior like the type of non-ionic surfactant and presence
      of solubilization enhancers were also studied. The fully dilutable microemulsion
      system that can incorporate high carvacrol amount, as revealed from the phase
      diagrams, was chosen for the antibacterial evaluation study. The same
      microemulsion system was re-formulated in a cationic form by substituting the non
      ionic surfactant, Tween 20 (T20) with the cationic cetylpyridinium chloride
      (CPC). The disc diffusion method was used to evaluate the activity of these
      microemulsion systems against different pathogenic bacteria. Results of the phase
      behavior study showed that carvacrol is a challenging phenolic compound which did
      not lend itself easily for solubilization in a fully dilutable non-ionic
      microemulsion. Incorporation of some solubilization enhancers like propylene
      glycol (PG) or short chain alcohols can fulfill this purpose however high
      surfactant/carvacrol ratio (9:1) was still required to solubilize only 1.0 wt%
      carvacrol in dilutable microemulsion. The antibacterial evaluation study at that
      concentration revealed that non-ionic carvacrol microemulsion formulated with T20
      and a solubilization enhancer did not exhibit better antimicrobial activity than
      the same concentration of carvacrol formulated in surfactant-free aqueous
      solution composed of water/PG (1:1). On the other hand, the CPC-formulated
      carvacrol microemulsion showed significantly higher antibacterial activity than
      T20-formulated microemulsion. Results of the current investigation shed the light
      on the solubilization capacity and phase behavior of carvacrol in non-ionic
      microemulsion and the potential of using cationic carvacrol microemulsion in
      disinfection and decontamination applications. 

PMID- 25766930
TI  - Effects of different fatty acid chain lengths on fatty acid oxidation-related
      protein expression levels in rat skeletal muscles.
AB  - Skeletal muscles can adapt to dietary interventions that affect energy
      metabolism. Dietary intake of medium-chain fatty acids (MCFAs) enhances
      mitochondrial oxidation of fatty acids (FAO) in type IIa skeletal muscle fibers.
      However, the effect of MCFAs diet on mitochondrial or cytoplasmic FAO-related
      protein expression levels in different types of muscle fibers remains unclear.
      This study aims to examine the effects of a high-fat diet, containing MCFAs, on
      mitochondrial enzyme activities and heart-type fatty acid-binding protein (H
      FABP) levels in different types of skeletal muscle fibers. Five-week-old male
      Wistar rats were assigned to one of the following three dietary conditions:
      standard chow (SC, 12% of calories from fat), high-fat MCFA, or high-fat long
      chain fatty acids (LCFAs) diet (60% of calories from fat for both). The animals
      were provided food and water ad libitum for 4 weeks, following which citrate
      synthase (CS) activity and H-FABP concentration were analyzed. The epididymal fat
      pads (EFP) were significantly smaller in the MCFA group than in the LCFA group (p
      < 0.05). MCFA-fed group displayed an increase in CS activity compared with that
      observed in SC-fed controls in all types of skeletal muscle fibers (triceps,
      surface portion of gastrocnemius (gasS), deep portion of gastrocnemius (gasD),
      and soleus; p < 0.05,). H-FABP concentration was significantly higher in the LCFA
      group than in both the SC-fed and MCFA-fed groups (triceps, gasS, gasD, and
      soleus; p < 0.05,). However, no significant difference was observed in the H-FABP
      concentrations between the SC-fed and MCFA-fed groups. The results of this study
      showed that the MCFA diet can increase the expression of the mitochondrial enzyme
      CS, but not that of H-FABP, in both fast- and slow-twitch muscle fibers,
      suggesting that H-FABP expression is dependent on the chain length of fatty acids
      in the cytoplasm of skeletal muscles cells. 

PMID- 25766931
TI  - Analysis of carbonyl value of frying oil by fourier transform infrared
      spectroscopy.
AB  - A rapid method for determining the carbonyl value of frying oils has been
      developed using Fourier-transform infrared (FTIR) spectroscopy and chemometrics.
      One hundred and fifty-six frying oils with different carbonyl values were
      collected from an actual potato frying process. FTIR spectra in the range of 4000
      650 cm(-1) were scanned with a FTIR spectroscopy apparatus using the attenuated
      total reflectance (ATR) method. A good calibration model was obtained using the
      partial least-squares (PLS) regression method with full cross validation for
      predicting the carbonyl value of frying oils. For the model, the coefficients of
      determination (R(2)), standard errors of cross validation (SECV) and standard
      errors of prediction (SEP) were 0.99, 1.87 MUmol g(-1) and 1.93 MUmol g(-1),
      respectively. Moreover, standard deviation ratios of reference data in the
      validation sample set to the SEP were higher than 3. This study shows that the
      carbonyl value of frying oils can be successfully determined to a high accuracy
      using FTIR spectroscopy combined with PLS regression. 

PMID- 25766932
TI  - O/W nano-emulsion formation using an isothermal low-energy emulsification method
      in a mixture of polyglycerol polyricinoleate and hexaglycerol monolaurate with
      glycerol system.
AB  - We investigated how phase behavior changes by replacing water with glycerol in
      water/mixture of polyglycerol polyricinoleate (PGPR) and hexaglycerol monolaurate
      (HGML) /vegetable oil system, and studied the effect of glycerol on o/w nano
      emulsion formation using an isothermal low-energy method. In the phase behavior
      study, the liquid crystalline phase (Lc) + the sponge phase (L3) expanded toward
      lower surfactant concentration when water was replaced with glycerol in a system
      containing surfactant HLP (a mixture of PGPR and HGML). O/W nano-emulsions were
      formed by emulsification of samples in a region of Lc + L3. In the
      glycerol/surfactant HLP/vegetable oil system, replacing water with glycerol was
      responsible for the expansion of a region containing Lc + L3 toward lower
      surfactant concentration, and as a result, in the glycerol/surfactant
      HLP/vegetable oil system, the region where o/w nano-emulsions or o/w emulsions
      could be prepared using an isothermal low-energy emulsification method was wide,
      and the droplet diameter of the prepared o/w emulsions was also smaller than that
      in the water/surfactant HLP/vegetable oil system. Therefore, glycerol was
      confirmed to facilitate the preparation of nano-emulsions from a system of
      surfactant HLP. Moreover, in this study, we could prepare o/w nano-emulsions with
      a simple one-step addition of water at room temperature without using a stirrer.
      Thus, the present technique is highly valuable for applications in several
      industries. 

PMID- 25766934
TI  - Lauric fat cocoa butter replacer from krabok (irvingia malayana) seed fat and
      coconut oil.
AB  - Lauric fat cocoa butter replacer (LCBR) was produced from a blend of krabok seed
      fat (KSF) and coconut oil (CO). Four fat blends with different ratios of KSF/CO
      (20/80, 40/60, 60/40 and 80/20 (%wt)), CO, KSF and a commercial LCBR (C-LCBR)
      were characterized using various techniques. It was found that blend 60/40
      exhibited SFC curve and crystallization/melting behavior most similar to that of
      C-LCBR. The blend met the requirements to be considered as LCBR and has potential
      as an alternative to commercial LCBR that are being used nowadays and hence it
      was recommended as LCBR (called R-LCBR). The polymorphic behavior of both C-LCBR
      and R-LCBR was investigated and both fats displayed mainly short spacing pattern
      associated with beta' polymorph, a required polymorph for LCBR. The compatibility
      between R-LCBR and CB was investigated by mixing the R-LCBR with CB in different
      proportions and softening due to the eutectic effect was observed in the mixed
      fats. This limits the proportion of CB and the R-LCBR in compound coatings to no
      more than 5% of CB in the total fat phase. 

PMID- 25766933
TI  - Bio-lubricants derived from waste cooking oil with improved oxidation stability
      and low-temperature properties.
AB  - Waste cooking oil (WCO) was chemically modified via epoxidation using H2O2
      followed by transesterification with methanol and branched alcohols (isooctanol,
      isotridecanol and isooctadecanol) to produce bio-lubricants with improved
      oxidative stability and low temperature properties. Physicochemical properties of
      synthesized bio-lubricants such as pour point (PP), cloud point (CP), viscosity,
      viscosity index (VI), oxidative stability, and corrosion resistant property were
      determined according to standard methods. The synthesized bio-lubricants showed
      improved low temperature flow performances compared with WCO, which can be
      attributing to the introduction of branched chains in their molecular structures.
      What's more, the oxidation stability of the WCO showed more than 10 folds
      improvement due to the elimination of -C=C-bonds in the WCO molecule.
      Tribological performances of these bio-lubricants were also investigated using
      four-ball friction and wear tester. Experimental results showed that derivatives
      of WCO exhibited favorable physicochemical properties and tribological
      performances which making them good candidates in formulating eco-friendly
      lubricants. 

PMID- 25766935
TI  - Lysophosphatidylcholine synthesis by lipase-catalyzed ethanolysis.
AB  - Lysophosphatidylcholine (LPC) is amphiphilic substance, and possesses excellent
      physiological functions. In this study, LPC was prepared through ethanolysis of
      phosphatidylcholine (PC) in n-hexane or solvent free media catalyzed by Novozym
      435 (from Candida antarctica), Lipozyme TLIM (from Thermomcyces lanuginosus) and
      Lipozyme RMIM (from Rhizomucor miehei). The results showed that three immobilized
      lipases from Candida Antarctica, Thermomcyces lanuginosus and Rhizomucor miehei
      could catalyze ethanolysis of PC efficiently. In n-hexane, the LPC conversions of
      ethanolysis of PC catalyzed by Novozyme 435, Lipozyme TLIM and Lipozyme RMIM
      could reach to 98.5 +/- 1.6%, 94.6 +/- 1.4% and 93.7 +/- 1.8%, respectively. In
      solvent free media, the highest LPC conversions of ethanolysis of PC catalyzed by
      Novozyme 435, Lipozyme TL IM and Lipozyme RM IM were 97.7 +/- 1.7%, 93.5 +/- 1.2%
      and 93.8 +/- 1.9%, respectively. The catalytic efficiencies of the three lipases
      were in the order of Novozyme 435 > Lipozyme TLIM > Lipozyme RMIM. Furthermore,
      their catalytic efficiencies in n-hexane were better than those in solvent free
      media. 

PMID- 25766936
TI  - Elucidating the effects of cholesterol on the molecular packing of double-chained
      cationic lipid langmuir monolayers by infrared reflection-absorption
      spectroscopy.
AB  - Cholesterol has been suggested to play a role in stable vesicle formation by
      adjusting the molecular packing of the vesicular bilayer. To explore the
      mechanisms involved in adjusting the bilayer structure by cholesterol, the
      molecular packing behavior in a mimic outer layer of cationic
      dialkyldimethylammonium bromide (DXDAB)/cholesterol vesicular bilayer was
      investigated by the Langmuir monolayer approach with infrared reflection
      absorption spectroscopy (IRRAS). The results indicated that the addition of
      cholesterol in the DXDAB Langmuir monolayers not only restrained the desorption
      of the DXDAB with short hydrocarbon chains, such as ditetradecyldimethylammonium
      bromide or dihexadecyldimethylammonium bromide, into the aqueous phase but also
      induced a condensing effect on the DXDAB monolayers. At a liquid-expanded (LE)
      state, the ordering effect of cholesterol accompanying the condensing effect
      occurred in the mixed DXDAB/cholesterol monolayers due to the tendency of
      maximizing hydrocarbon chain contact between cholesterol and the neighboring
      hydrocarbon chains. However, for the mixed monolayers containing the DXDAB with
      long hydrocarbon chains, such as dioctadecyldimethylammonium bromide (DODAB), the
      disordering effect of cholesterol took place at a liquid-condensed (LC) state.
      This was related to the molecular structure of cholesterol and hydrocarbon chain
      length of DODAB. The rigid sterol ring of cholesterol hindered the portion of
      neighboring hydrocarbon chains from motion. However, the flexible alkyl side
      chain of cholesterol along with the corresponding portion of neighboring
      hydrocarbon chains formed a fluidic region, counteracting the enhanced
      conformational order induced by the sterol ring of cholesterol. Furthermore, the
      long hydrocarbon chains of DODAB possessed a more pronounced motion freedom,
      resulting in a more disordered packing of the monolayers. 

PMID- 25766937
TI  - Paradoxical widespread c-Fos expression induced by a GABA agonist in the
      forebrain of transgenic mice with ectopic expression of the GABA(A) alpha6
      subunit.
AB  - A GABA-site agonist gaboxadol (4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridin-3-ol) at
      3 mg/kg induces strong anxiolytic response in a transgenic Thy1alpha6 mouse line
      ectopically expressing the GABA(A) receptor alpha6 subunit gene under the Thy-1.2
      promoter. Now, we compared brain activation patterns between Thy1alpha6 and wild
      type mice to identify brain structures potentially mediating this anxiolytic
      response. Acutely efficient anxiolytics such as benzodiazepines typically depress
      most brain regions while activating specifically neurons within the central
      extended amygdala. Gaboxadol treatment (3 mg/kg, i.p., 2 h) induced a significant
      increase in c-Fos expression selectively in many Thy1alpha6 brain regions
      including the limbic cortex, anterior olfactory nucleus, septal area and central
      and basolateral nuclei of amygdala. It failed to activate the lateral part of
      mediodorsal thalamic nucleus (MDL) in the Thy1alpha6 mice that was activated in
      the wild-type mice. Detailed mapping of the alpha6 subunit mRNA by in situ
      hybridization revealed expression in the middle layers of the isocortex,
      olfactory areas, hippocampal formation and basolateral nucleus of amygdala (BLA)
      in the Thy1alpha6 forebrain. The ligand autoradiographies (t
      butylbicyclophosphoro[(35)S]thionate ([(35)S]TBPS) and [(3)H]Ro 15-4513) revealed
      high levels of pharmacologically active extrasynaptic alpha6beta and
      alpha6betagamma2 GABA(A) receptors in these same areas. However, c-Fos induction
      by gaboxadol treatment in Thy1alpha6 brain was not restricted to areas highly
      expressing the alpha6-containing GABA(A) receptors suggesting that indirect
      pathways lead to the paradoxically widespread activation. Interestingly, the
      activation pattern by gaboxadol at the dose that is anxiolytic in Thy1alpha6 mice
      resembled closely that observed after various fear- and stress-provoking
      challenges. However, our results are consistent with a recent observation that
      optogenetic activation of specific neuronal pathways in the extended amygdala
      mediates anxiolytic responses. Our results suggest that the widespread neuronal
      inhibition as typically associated with benzodiazepines is not the exclusive
      mechanism of anxiolysis.

PMID- 25766938
TI  - Spatial cognitive deficits in an animal model of Wernicke-Korsakoff syndrome are
      related to changes in thalamic VDAC protein concentrations.
AB  - Proteomic profiles of the thalamus and the correlation between the rats'
      performance on a spatial learning task and differential protein expression were
      assessed in the thiamine deficiency (TD) rat model of Wernicke-Korsakoff
      syndrome. Two-dimensional gel-electrophoresis detected 320 spots and a
      significant increase or decrease in seven proteins. Four proteins were correlated
      to rat behavioral performance in the Morris Water Maze. One of the four proteins
      was identified by mass spectrometry as Voltage-Dependent Anion Channels (VDACs).
      The association of VDAC is evident in trials in which the rats' performance was
      worst, in which the VDAC protein was reduced, as confirmed by Western blot. No
      difference was observed on the mRNA of Vdac genes, indicating that the decreased
      VDAC expression may be related to a post-transcriptional process. The results
      show that TD neurodegeneration involves changes in thalamic proteins and suggest
      that VDAC protein activity might play an important role in an initial stage of
      the spatial learning process.

PMID- 25766939
TI  - Seasonal distribution of pharmaceuticals in marine water and sediment from a
      Mediterranean coastal lagoon (SE Spain).
AB  - The seasonal variations in the occurrence and distribution of pharmaceuticals
      were evaluated in seawater and sediment of Mar Menor lagoon from spring 2010 to
      winter 2011. A total of 20 pharmaceuticals in seawater and 14 in sediments were
      found at concentrations from low ngL(-)(1) up to 168ngL(-)(1) (azithromycin) in
      seawater and from low ngg(-1) up to 50.3ngg(-1) (xylazine) in sediments.
      Azithromycin, xylazine and metoprolol were the most ubiquitous compounds in
      seawater since they were found in all seawater samples collected. Seven compounds
      were quantified in both matrices: clarithromycin, erythromycin,
      hydrochlorothiazide, irbesartan, losartan, salicylic acid and valsartan. Seasonal
      distribution profiles revealed different sources of pollutants associated to
      both, El Albujon watercourse (which receives the input of a WWTP) and other non
      controlled discharges, into the lagoon. In summer the highest concentrations in
      seawater for most of the pharmaceuticals were detected close to main touristic
      nuclei, probably as consequence of sources such as the excretion from bathers
      and/or other non-controlled discharges, these being significantly higher than in
      autumn and winter for antibiotics. On the contrary, the mean concentration of
      lorazepam was significantly higher in colder seasons than in warmer ones.
      Sulfamethoxazole, erythromycin and especially clarithromycin showed hazard
      quotients higher than 1 in seawater at some areas of this lagoon indicating a
      potential risk to aquatic organisms in such specific areas. 

PMID- 25766940
TI  - Spermatogenic capacity in fertile men with elevated exposure to polychlorinated
      biphenyls.
AB  - BACKGROUND: Endocrine disrupting industrial chemicals, such as polychlorinated
      biphenyls (PCBs), are suspected to adversely affect male reproductive functions.
      OBJECTIVES: The Faroe Islands community exhibits an unusually wide range of
      exposures to dietary contaminants, and in this setting we examined the possible
      association between PCB exposure and semen quality and reproductive hormones in
      fertile Faroese men. METHODS: Participants in this cross-sectional study include
      266 proven fertile men residing in the Faroe Islands. PCB levels and hormone
      profiles were measured in serum samples taken at the clinical examination that
      included semen quality parameters. RESULTS: A significant positive association
      was seen between serum-PCB and the testosterone/estradiol ratio (p=0.04). In the
      unadjusted analyses, elevated PCB exposure was associated with increased serum
      concentrations of SHBG (p=0.01) and FSH (p=0.05). We found no association between
      the serum PCB concentration and the semen quality variables. CONCLUSION: In this
      population of highly exposed fertile men, the current serum-PCB concentration was
      associated with higher androgen/estrogen ratio. Further studies are needed to
      establish the findings and further document PCB-associated hormonal effects, any
      time windows of increased susceptibility, and the role of PCB in sub-fecundity.

PMID- 25766942
TI  - Do we really know the CvLPRIT in Myocardial infarction? or just stent all
      lesions?

PMID- 25766941
TI  - Randomized trial of complete versus lesion-only revascularization in patients
      undergoing primary percutaneous coronary intervention for STEMI and multivessel
      disease: the CvLPRIT trial.
AB  - BACKGROUND: The optimal management of patients found to have multivessel disease
      while undergoing primary percutaneous coronary intervention (P-PCI) for ST
      segment elevation myocardial infarction is uncertain. OBJECTIVES: CvLPRIT
      (Complete versus Lesion-only Primary PCI trial) is a U.K. open-label randomized
      study comparing complete revascularization at index admission with treatment of
      the infarct-related artery (IRA) only. METHODS: After they provided verbal assent
      and underwent coronary angiography, 296 patients in 7 U.K. centers were
      randomized through an interactive voice-response program to either in-hospital
      complete revascularization (n = 150) or IRA-only revascularization (n = 146).
      Complete revascularization was performed either at the time of P-PCI or before
      hospital discharge. Randomization was stratified by infarct location
      (anterior/nonanterior) and symptom onset (<= 3 h or >3 h). The primary endpoint
      was a composite of all-cause death, recurrent myocardial infarction (MI), heart
      failure, and ischemia-driven revascularization within 12 months. RESULTS: Patient
      groups were well matched for baseline clinical characteristics. The primary
      endpoint occurred in 10.0% of the complete revascularization group versus 21.2%
      in the IRA-only revascularization group (hazard ratio: 0.45; 95% confidence
      interval: 0.24 to 0.84; p = 0.009). A trend toward benefit was seen early after
      complete revascularization (p = 0.055 at 30 days). Although there was no
      significant reduction in death or MI, a nonsignificant reduction in all primary
      endpoint components was seen. There was no reduction in ischemic burden on
      myocardial perfusion scintigraphy or in the safety endpoints of major bleeding,
      contrast-induced nephropathy, or stroke between the groups. CONCLUSIONS: In
      patients presenting for P-PCI with multivessel disease, index admission complete
      revascularization significantly lowered the rate of the composite primary
      endpoint at 12 months compared with treating only the IRA. In such patients,
      inpatient total revascularization may be considered, but larger clinical trials
      are required to confirm this result and specifically address whether this
      strategy is associated with improved survival.

PMID- 25766943
TI  - Pre-frailty and risk of cardiovascular disease in elderly men and women: the
      Pro.V.A. study.
AB  - BACKGROUND: Frailty is an important risk factor for cardiovascular disease (CVD),
      but the impact of early, potentially reversible stages of frailty on CVD risk is
      unknown. OBJECTIVES: This study sought to ascertain whether pre-frailty can
      predict the onset of CVD in a cohort of community-dwelling, not disabled, elderly
      people. METHODS: A sample of 1,567 participants age 65 to 96 years without
      frailty or disability at baseline was followed for 4.4 years. Pre-frailty was
      defined as the presence of 1 or 2 modified Fried criteria (unintentional weight
      loss, low physical activity level, weakness, exhaustion, and slow gait speed),
      and incident CVD as onset of coronary artery diseases, heart failure, stroke,
      peripheral artery disease, or CVD-related mortality. RESULTS: During follow-up,
      551 participants developed CVD. Compared with participants who did not become
      frail, those with 1 modified Fried criterion (p = 0.03) and those with 2 criteria
      (p = 0.001) had a significantly higher risk of CVD, even after adjusting for
      several potential confounders (traditional risk factors for CVD, inflammatory
      markers, and hemoglobin A1c levels). Low energy expenditure (p = 0.03),
      exhaustion (p = 0.01), and slow gait speed (p = 0.03) were significantly
      associated with the onset of CVD, whereas unintentional weight loss and weakness
      were not. CONCLUSIONS: Our findings suggest that pre-frailty, which is
      potentially reversible, is independently associated with a higher risk of older
      adults developing CVD. Among the physical domains of pre-frailty, low gait speed
      seems to be the best predictor of future CVD.

PMID- 25766944
TI  - Which came first, the frailty or the heart disease?: exploring the vicious cycle.

PMID- 25766945
TI  - Importance of CMR within the Task Force Criteria for the diagnosis of ARVC in
      children and adolescents.
AB  - BACKGROUND: Cardiac magnetic resonance (CMR) is a component of the revised Task
      Force Criteria (rTFC) for the diagnosis of arrhythmogenic right ventricular
      cardiomyopathy (ARVC). However, its diagnostic value in a pediatric population is
      unknown. OBJECTIVES: This study examined the contribution of CMR to diagnosing
      ARVC using the rTFC in a pediatric population. METHODS: Clinical CMR studies of
      142 pediatric patients evaluated for ARVC between 2005 and 2009 were reviewed.
      Patients were categorized into "definitive," "borderline," "possible," or "no"
      ARVC diagnostic groups based on the rTFC. The extent to which each element of the
      rTFC contributed to diagnosing ARVC was determined using a c-statistics model.
      RESULTS: A total of 23 (16%), 32 (23%), 37 (26%), and 50 (35%) patients had
      definite, borderline, possible, and no ARVC, respectively, applying the rTFC. The
      prevalence of regional wall motion abnormalities in these groups was 83%, 53%,
      22%, and 16%, respectively (p < 0.001). By CMR, right ventricular end-diastolic
      volumes were 118 +/- 31 cc/m2, 108 +/- 22 cc/m2, 94 +/- 14 cc/m2, and 92 +/- 18
      cc/m2, respectively (p < 0.001). Right ventricular fatty infiltration and
      fibrosis were detected in only 1 and 3 patients, respectively, all of whom had
      definitive ARVC. Of all rTFC major criteria, CMR had the largest c-statistic
      decline (c = -0.163). Eleven of the 23 patients (48%) with definite ARVC would
      not have been in this group if CMR had not been performed. CONCLUSIONS: CMR
      parameters are important contributors to a diagnosis of ARVC in children, using
      the rTFC. Fatty infiltration and myocardial fibrosis provide limited value in
      children and adolescents.

PMID- 25766946
TI  - Imaging criteria for arrhythmogenic right ventricular cardiomyopathy: an
      incomplete journey.

PMID- 25766948
TI  - Intervention or exercise?: the answer is yes!

PMID- 25766950
TI  - Cardiovascular health: China's choices.

PMID- 25766947
TI  - Supervised exercise, stent revascularization, or medical therapy for claudication
      due to aortoiliac peripheral artery disease: the CLEVER study.
AB  - BACKGROUND: Treatment for claudication that is due to aortoiliac peripheral
      artery disease (PAD) often relies on stent revascularization (ST). However,
      supervised exercise (SE) is known to provide comparable short-term (6-month)
      improvements in functional status and quality of life. Longer-term outcomes are
      not known. OBJECTIVES: The goal of this study was to report the longer-term (18
      month) efficacy of SE compared with ST and optimal medical care (OMC). METHODS:
      Of 111 patients with aortoiliac PAD randomly assigned to receive OMC, OMC plus
      SE, or OMC plus ST, 79 completed the 18-month clinical and treadmill follow-up
      assessment. SE consisted of 6 months of SE and an additional year of telephone
      based exercise counseling. Primary clinical outcomes included objective treadmill
      based walking performance and subjective quality of life. RESULTS: Peak walking
      time improved from baseline to 18 months for both SE (5.0 +/- 5.4 min) and ST
      (3.2 +/- 4.7 min) significantly more than for OMC (0.2 +/- 2.1 min; p < 0.001 and
      p = 0.04, respectively). The difference between SE and ST was not significant (p
      = 0.16). Improvement in claudication onset time was greater for SE compared with
      OMC, but not for ST compared with OMC. Many disease-specific quality-of-life
      scales demonstrated durable improvements that were greater for ST compared with
      SE or OMC. CONCLUSIONS: Both SE and ST had better 18-month outcomes than OMC. SE
      and ST provided comparable durable improvement in functional status and in
      quality of life up to 18 months. The durability of claudication exercise
      interventions merits its consideration as a primary PAD claudication treatment.

PMID- 25766949
TI  - Status of cardiovascular health in Chinese adults.
AB  - BACKGROUND: Cardiovascular disease has become the leading cause of death in
      China. OBJECTIVES: The goal of this study was to evaluate the current status of
      cardiovascular health in Chinese adults. METHODS: Cardiovascular health data were
      collected from a nationally representative sample of 96,121 Chinese adults age >=
      20 years in 2010. Ideal cardiovascular health was defined according to the
      American Heart Association's 2020 Strategic Impact Goals as follows: the
      simultaneous presence of 4 favorable health behaviors (ideal smoking status,
      ideal body mass index, physical activity at goal, and healthy dietary habits) and
      4 favorable health factors (ideal smoking status, untreated total cholesterol
      <200 mg/dl, untreated blood pressure <120/<80 mm Hg, and untreated fasting plasma
      glucose <100 mg/dl) in the absence of a history of cardiovascular disease.
      RESULTS: The estimated percentage of ideal cardiovascular health was 0.2% in the
      general adult population in China (0.1% in men and 0.4% in women). An estimated
      0.7% (0.4% in men and 1.0% in women) of Chinese adults had all 4 ideal health
      behaviors, and 13.5% (5.0% in men and 22.3% in women) had all 4 ideal health
      factors. Men most frequently had 3 to 4 ideal components, and women most commonly
      had 4 to 5 ideal components of the 7 cardiovascular health metrics. Ideal diet
      (1.6%) was the least common among all cardiovascular health metrics. Female sex
      and younger age were the 2 most common protective factors for cardiovascular
      health in Chinese adults. CONCLUSIONS: The percentage of ideal cardiovascular
      health in Chinese adults is extremely low. Both population-wide and high-risk
      strategies should be implemented with great effort to promote cardiovascular
      health in China.

PMID- 25766951
TI  - The path to an angiotensin receptor antagonist-neprilysin inhibitor in the
      treatment of heart failure.
AB  - The PARADIGM-HF (Prospective comparison of ARNi with ACEi to Determine Impact on
      Global Mortality and Morbidity in Heart Failure) trial demonstrated that a new
      angiotensin receptor antagonist-neprilysin inhibitor was superior to an
      angiotensin-converting enzyme inhibitor in reducing mortality in patients with
      heart failure and reduced ejection fraction. This paper traces the research path
      that culminated in the development of this drug. The first phase, elucidation of
      the renin-angiotensin-aldosterone system, began with Tigerstedt's discovery of
      renin, followed by isolation of angiotensin, isolation of angiotensin-converting
      enzyme, and synthesis of its inhibitors and of angiotensin receptor blockers.
      Phase 2 began with de Bold's discovery of atrial natriuretic peptide, followed by
      isolation of the enzyme that degrades it (neprilysin) and its inhibitors. Phase 3
      consists of blocking both the renin-angiotensin-aldosterone and atrial
      natriuretic peptide-degrading systems simultaneously. A molecular complex,
      LCZ696, developed by scientists at Novartis, combines an angiotensin receptor
      blocker with a neprilysin inhibitor, is well tolerated, and represents an
      important step in the management of heart failure and reduced ejection fraction. 

PMID- 25766953
TI  - Challenging inertia by taking risks: a motivating tool for editors, authors, and
      students.

PMID- 25766954
TI  - Launching the new American College of Cardiology Research Network: advancing high
      value collaborative research via "innovative networking".

PMID- 25766952
TI  - Dietary sodium and health: more than just blood pressure.
AB  - Sodium is essential for cellular homeostasis and physiological function. Excess
      dietary sodium has been linked to elevations in blood pressure (BP). Salt
      sensitivity of BP varies widely, but certain subgroups tend to be more salt
      sensitive. The mechanisms underlying sodium-induced increases in BP are not
      completely understood but may involve alterations in renal function, fluid
      volume, fluid-regulatory hormones, the vasculature, cardiac function, and the
      autonomic nervous system. Recent pre-clinical and clinical data support that even
      in the absence of an increase in BP, excess dietary sodium can adversely affect
      target organs, including the blood vessels, heart, kidneys, and brain. In this
      review, the investigators review these issues and the epidemiological research
      relating dietary sodium to BP and cardiovascular health outcomes, addressing
      recent controversies. They also provide information and strategies for reducing
      dietary sodium. 

PMID- 25766955
TI  - Cardiac determinants of heterogeneity in fitness change in response to moderate
      intensity aerobic exercise training: the DREW study.

PMID- 25766956
TI  - Aortic calcifications present the next challenge after TAVR.

PMID- 25766957
TI  - Considerations for drug development for heart failure.

PMID- 25766958
TI  - Reply: considerations for drug development for heart failure.

PMID- 25766959
TI  - Short-term mechanical circulatory support: the problem of the uninsured.

PMID- 25766960
TI  - Administrative data: proceed with caution.

PMID- 25766961
TI  - Reward responsiveness in patients with chronic pain.
AB  - BACKGROUND: It is proposed that changes in reward processing in the brain are
      involved in the pathophysiology of pain based on experimental studies. The first
      aim of the present study was to investigate if reward drive and/or reward
      responsiveness was altered in patients with chronic pain (PCP) compared to
      controls matched for education, age and sex. The second aim was to investigate
      the relationship between reward processing and nucleus accumbens volume in PCP
      and controls. Nucleus accumbens is central in reward processing and its structure
      has been shown to be affected by chronic pain conditions in previous studies.
      METHODS: Reward drive and responsiveness were assessed with the Behavioral
      Inhibition Scale/Behavioral Activation Scale, and nucleus accumbens volumes
      obtained from T1-weighted brain MRIs obtained at 3T in 19 PCP of heterogeneous
      aetiologies and 20 age-, sex- and education-matched healthy controls. Anhedonia
      was assessed with Beck's Depression Inventory II. RESULTS: The PCP group had
      significantly reduced scores on the reward responsiveness, but not reward drive.
      There was a trend towards smaller nucleus accumbens volume in the PCP compared to
      control group. There was a significant positive partial correlation between
      reward responsiveness and nucleus accumbens volume in the PCP group adjusted for
      anhedonia, which was significantly different from the same relationship in the
      control group. CONCLUSIONS: Reward responsiveness is reduced in chronic pain
      patients of heterogeneous aetiology, and this reduction was associated with
      nucleus accumbens volume. Reduced reward responsiveness could be a marker of
      chronic pain vulnerability, and may indicate reduced opioid function.

PMID- 25766962
TI  - Editors' Picks for 2014 and a Look into the Future.

PMID- 25766963
TI  - MPs criticise "diluted" priority for cancer services over past two years.

PMID- 25766965
TI  - Amine-catalyzed tunable reactions of allenoates with dithioesters: formal [4+2]
      and [2+2] cycloadditions for the synthesis of 2,3-dihydro-1,4-oxathiines and
      enantioenriched thietanes.
AB  - The chemoselective [4+2] vs. [2+2] cycloaddition between allenoates and
      dithioesters can be controlled by switching the nucleophilic amine catalyst. The
      two modes of cyclizations represent the first example of controllable and
      chemoselective annulations between allenoates and dienophiles catalyzed by amine.
      These cyclizations are useful in offering a divergent synthesis of sulfur
      containing heterocycles. On the basis of this investigation, it can be realized
      that dithioesters with a vicinal electron-withdrawing group can react not only
      like a Michael acceptor but also as a ketone or imine. 

PMID- 25766964
TI  - The Relationship Between Cochleovestibular Orientation, Age, and Sensorineural
      Hearing Loss: Implications for Cochlear Implantation.
AB  - OBJECTIVES: To determine if spatial orientation of the cochlea within the
      temporal bone is related to age or sensorineural hearing loss (SNHL) and describe
      the implications for cochlear implantation. METHODS: Five angles of cochlear
      orientation were determined from computed tomography (CT) imaging of the temporal
      bones in adults with (n = 55) and without (n = 27) sensorineural hearing loss
      (SNHL) and children with (n = 45) and without (n = 12) SNHL: facial recess versus
      basal turn, posterior semicircular canal versus basal turn, round window versus
      basal turn (axial view), round window versus basal turn (coronal view), and the
      cochlear axis versus the mastoid facial nerve. RESULTS: All angles showed
      substantial variation between subjects and between ears. The angles between the
      round window and basal turn (coronal view) and the posterior semicircular canal
      and basal turn were significantly correlated with age for all subjects with SNHL
      (r = 0.22, P = .002 and r = 0.15, P = .03, respectively). Patients with SNHL had
      significantly more acute angles (46.6 degrees  vs 55.8 degrees ) between the
      round window versus basal turn (axial orientation) compared to controls (P <
      .001). CONCLUSIONS: Cochlear orientation within the temporal bone changes with
      age and the degree of SNHL. These results suggest that the approach to the round
      window for electrode insertion might differ between children and adults.

PMID- 25766966
TI  - Endothelial dysfunction and metabolic syndrome in preeclampsia: an alternative
      viewpoint.
AB  - Several clinical and basic science reports have elucidated partial aspects of the
      pathophysiology of preeclampsia and have led many authors to conclude that
      different "subtypes" of the disease exist. All these subtypes share the main
      clinical features of the disease and present additional characteristics that
      define different clinical phenotypes. Nevertheless, immunological alterations,
      endothelial dysfunction, and insulin resistance constantly characterize this
      syndrome. These aspects are intimately related at a molecular level; thus, we
      propose an alternative approach to explaining biologically the main intracellular
      processes that occur in preeclampsia and this may yield an insight into the
      pathogenesis. 

PMID- 25766967
TI  - Comparing perfusion CT evaluation algorithms for predicting outcome after
      endovascular treatment in anterior circulation ischaemic stroke.
AB  - AIM: To analyse perfusion CT (PCT) evaluation algorithms for their predictive
      value for outcome after endovascular therapy (ET) in acute ischaemic stroke.
      MATERIALS AND METHODS: Twenty-six patients were prospectively enrolled to undergo
      endovascular therapy for moderate to severe [National Institute of Health Stroke
      Scale (NIHSS) score of >=5] anterior circulation stroke <=6 h of onset. PCT
      datasets were evaluated according to three algorithms: visual mismatch estimate
      (VME), Alberta Stroke Programme Early CT Score (ASPECTS) perfusion, and
      quantitative perfusion ratios (QPRs: RCBF, RCBV) of cerebral blood flow (CBF) and
      volume (CBV). Results were correlated with outcome measures [NIHSS score at
      discharge, NIHSS score change until discharge (DeltaNIHSSA/D), mRS at 90 days
      (mRS90d)] and compared with a matched control group. RESULTS: Recanalization was
      achieved in 73%, median NIHSS score decreased from 14 to 5 at discharge. The
      treatment and control group did not differ by VME and ASPECTS perfusion, nor did
      VME correlate with any of the three outcome measures. ASPECTS perfusion was not
      predictive of any outcome measure in the ET group. RCBF and RCBV were associated
      with DeltaNIHSSA/D in controls and, inversely, the ET group, but not with mRS90d.
      Receiver operating characteristic (ROC) analysis of RCBF (and RCBV) showed a
      positive predictive and negative predictive value of 87% (78%) and 74% (73%),
      respectively, for discriminating major neurological improvement (DeltaNIHSSA/D <7
      versus >=7). CONCLUSIONS: Implementation of QPRs for CBF and CBV are superior to
      clinically used VME and ASPECTS perfusion evaluation methods for predicting early
      outcome after ET for anterior circulation stroke.

PMID- 25766968
TI  - Brain imaging in lung cancer patients without symptoms of brain metastases: a
      national survey of current practice in England.
AB  - AIM: To determine current practice regarding brain imaging for newly diagnosed
      lung cancer patients without symptoms of brain metastases. MATERIALS AND METHODS:
      A survey questionnaire was sent by e-mail to all the lung cancer lead clinicians
      in England currently on the National Cancer Intelligence Network database. The
      survey asked whether brain imaging was used in new lung cancer patients without
      symptoms or signs to suggest brain metastases; and if so, which patient subgroups
      were imaged according to cell type, stage of disease, and intention to treat, and
      which techniques were used to image these patients. Responses were received
      between February and May 2014. RESULTS: Fifty-nine of 154 centres replied to the
      survey (38%). Thirty of the 59 centres (51%) did not image the brain in these
      patients. Twenty-nine of the 59 (49%) centres imaged the brain in at least
      certain subgroups. Of those centres that did image the brain 21 (72%) used CT as
      the first-line imaging technique and six (20%) used MRI. Twenty-five of 59 (42%)
      centres stated that the 2011 NICE guidelines had led to a change in their
      practice. CONCLUSION: There is wide variation in practice regarding brain imaging
      in this patient group in England, with no brain imaging at all in approximately
      half of centres and a spectrum of imaging in the other half. When the brain is
      imaged, CT is the technique most commonly used. The 2011 NICE guidelines have led
      to some change in practice but not to national uniformity.

PMID- 25766969
TI  - Inhomogeneity of the amorphous solid water dangling bonds.
AB  - Amorphous solid water (ASW) is one of the most widely studied molecular systems
      because of its importance in the physics and chemistry of the interstellar medium
      and the upper layers of the Earth's atmosphere. Although the global structure of
      this material, i.e. the bulk and the surface, is well characterised, we are far
      from having an overall understanding of the changes induced upon chemical or
      physical perturbation. More specifically, the behaviour of the surface and the
      immediate sublayers upon mid-infrared irradiation must be understood due to its
      direct effect on the adsorption capacities of the ASW surface. Small molecules
      can accrete or form at the surface, adsorbed on the dangling OH groups of surface
      water molecules. This behaviour allows further reactivity which, in turn, could
      lead to more complex molecular systems. We have already demonstrated that
      selective IR irradiations of surface water molecules induce a modification of the
      surface and the production of a new monomer species which bonds to the surface
      via its two electronic doublets. However, we did not probe the structure of the
      dangling bands, namely their homogeneity or inhomogeneity. The structure and
      orientation of these surface molecules are closely linked to the way the surface
      can relax its vibrational energy. In this work, we have focussed our attention on
      the two dH dangling bonds, carrying out a series of selective irradiations which
      reveal the inhomogeneity of these surface modes. We have also studied the effects
      of irradiation duration on the surface reorientation, determining that the
      maximum photoinduced isomerisation yield is ~15%. 

PMID- 25766970
TI  - Electrocardiographic prediction of lateral involvement in acute non-anterior wall
      myocardial infarction.
AB  - PURPOSE: Recent research has established that a tall R-wave in V1 indicates
      lateral wall involvement in non-anterior wall myocardial infarction (MI). The
      objective of this study was to assess the value of the admission
      electrocardiogram (ECG) to predict R-waves and consequently lateral wall damage
      in the late phase of non-anterior MI. METHODS: ECGs of 69 patients were analyzed.
      ST-segment changes in representative leads for lateral wall infarction such as
      V1, V2, V6 and I were correlated with the extent of QRS-wave changes in V1 and
      V6. RESULTS: ST-segment elevation in V6 showed correlations with R/S ratio in V1
      (r=0.802, B=0.440, P=<0.001) and with the depth of Q-waves in V6 (r=0.671,
      B=0.441, P=0.007). This correlation was higher in a small subgroup where the left
      circumflex branch (Cx) was the culprit vessel (r=0.888, B=1.469 and P=0.018). ST
      segment depression in lead I correlated with the height of R and the surface of R
      in V1 (height times width of R) (r=0.542, B=-0.150, P=0.005 and r=0.538, B=
      0.153, P=0.005 respectively), especially in the subgroup without proximal
      occlusions of RCA (r=0.711 and r=0.699). ST-segment depression in lead I also
      predicted Q-waves in V6 (r=0.538, B=0.114, P=0.006). ST-segment changes in V2
      showed no significant correlation with either R- or Q-wave measurements.
      CONCLUSIONS: ST-segment elevation in V6 in the acute phase of non-anterior MI
      predicts lateral involvement as expressed by the R/S ratio in V1 in the post
      reperfusion phase. A subgroup with Cx occlusion showed especially strong
      correlations, although the size of the group was small. In lead I ST-segment
      depression is correlated to height and surface of R in V1 and Q-waves in V6.

PMID- 25766971
TI  - New paradigms for the chiral synthesis of inositol phosphates.
AB  - Paradigms found: Inositol phosphates are biomolecules found ubiquitously in
      eukaryotes, in which they play a number of vital biological roles. Their
      enantioselective synthesis has recently received a boost from two complementary
      phosphorylation methods that could change the way they are synthesised, and
      hopefully provide invaluable chemical biology tools to further our understanding
      of this large family. 

PMID- 25766972
TI  - Improving cancer clinical research and trials with Hispanic populations: training
      and outreach efforts between Moffitt Cancer Center and the Ponce School of
      Medicine.

PMID- 25766973
TI  - Low-molecular-weight heparins and cancer: focus on antitumoral effect.
AB  - A close relationship between cancer and thrombosis does exist, documented by the
      fact that an overall 7-fold increased risk of venous thromboembolism (VTE) has
      been reported in patients with malignancy compared to non-malignancy. The
      potential impact of antithrombotic agents in cancer-associated VTE has long been
      recognized, and, in particular, several clinical trials in the last 20 years have
      reported the safety and efficacy of low-molecular-weight heparins (LMWHs) for
      treatment and prophylaxis of VTE in patients with various types of cancer. More
      recently, a number of preclinical and clinical studies have suggested that LMWHs
      may improve survival in cancer patients with mechanisms that are different from
      its antithrombotic effect but are linked to the ability of influencing directly
      the tumor biology. This paper reviews the evidence around the potential survival
      benefits of LMWHs by analyzing the suggested mechanisms and the available
      clinical data. 

PMID- 25766974
TI  - Flow velocity waveforms of the ductus venosus and atrioventricular valves in a
      case of fetal hemangiolymphangioma.

PMID- 25766975
TI  - Copper-mediated ortho C-H sulfonylation of benzoic acid derivatives with sodium
      sulfinates.
AB  - Copper-mediated direct ortho C-H bond sulfonylation of benzoic acid derivatives
      with sodium sulfinates was achieved by employing an 8-aminoquinoline moiety as
      the bidentate directing group. Various aryl sulfones were synthesized in good
      yields with excellent regioselectivity. 

PMID- 25766976
TI  - Refinement of a thermal threshold probe to prevent burns.
AB  - Thermal threshold testing is commonly used for pain research. The stimulus may
      cause burning and merits prevention. Thermal probe modifications hypothesized to
      reduce burning were evaluated for practicality and effect. Studies were conducted
      on two humans and eight cats. Unmodified probe 0 was tested on two humans and
      promising modifications were also evaluated on cats. Probe 1 incorporated rapid
      cooling after threshold was reached: probe 1a used a Peltier system and probe 1b
      used water cooling. Probe 2 released skin contact immediately after threshold.
      Probe 3 (developed in the light of evidence of 'hot spots' in probe 0)
      incorporated reduced thermal mass and even heating across the skin contact area.
      Human skin was heated to 48C (6C above threshold) and the resulting burn was
      evaluated using area of injury and a simple descriptive scale (SDS). Probe 1a
      cooled the skin but required further heat dissipation, excessive power, was not
      'fail-safe' and was inappropriate for animal mounting. Probe 1b caused less
      damage than no cooling (27 +/- 13 and 38 +/- 11 mm(2) respectively, P = 0.0266;
      median SDS 1.5 and 4 respectively, P = 0.0317) but was cumbersome. Probe 2 was
      unwieldy and was not evaluated further. Probe 3 produced even heating without
      blistering in humans. With probe 3 in cats, after opioid treatment, thermal
      threshold reached cut-out (55C) on 24 occasions, exceeded 50C in a further 32
      tests and exceeded 48C in the remainder. No skin damage was evident immediately
      after testing and mild hyperaemia in three cats at 2-3 days resolved rapidly.
      Probe 3 appeared to be suitable for thermal threshold testing.

PMID- 25766977
TI  - Indoor air quality, ventilation and respiratory health in elderly residents
      living in nursing homes in Europe.
AB  - Few data exist on respiratory effects of indoor air quality and comfort
      parameters in the elderly. In the context of the GERIE study, we investigated for
      the first time the relationships of these factors to respiratory morbidity among
      elderly people permanently living in nursing homes in seven European countries.
      600 elderly people from 50 nursing homes underwent a medical examination and
      completed a standardised questionnaire. Air quality and comfort parameters were
      objectively assessed in situ in the nursing home. Mean concentrations of air
      pollutants did not exceed the existing standards. Forced expiratory volume in 1
      s/forced vital capacity ratio was highly significantly related to elevated levels
      of particles with a 50% cut-off aerodynamic diameter of <0.1 um (PM0.1) (adjusted
      OR 8.16, 95% CI 2.24-29.3) and nitrogen dioxide (aOR 3.74, 95% CI 1.06-13.1).
      Excess risks for usual breathlessness and cough were found with elevated PM10
      (aOR 1.53 (95% CI 1.15-2.07) and aOR 1.73 (95% CI 1.17-10.3), respectively) and
      nitrogen dioxide (aOR 1.58 (95% CI 1.15-2.20) and aOR 1.56 (95% CI 1.03-2.41),
      respectively). Excess risks for wheeze in the past year were found with PM0.1
      (aOR 2.82, 95% CI 1.15-7.02) and for chronic obstructive pulmonary disease and
      exhaled carbon monoxide with formaldehyde (aOR 3.49 (95% CI 1.17-10.3) and aOR
      1.25 (95% CI 1.02-1.55), respectively). Breathlessness and cough were associated
      with higher carbon dioxide. Relative humidity was inversely related to wheeze in
      the past year and usual cough. Elderly subjects aged >=80 years were at higher
      risk. Pollutant effects were more pronounced in the case of poor ventilation.
      Even at low levels, indoor air quality affected respiratory health in elderly
      people permanently living in nursing homes, with frailty increasing with age. The
      effects were modulated by ventilation.

PMID- 25766978
TI  - Expression of BKV and JCV encoded microRNA in human cerebrospinal fluid, plasma
      and urine.
AB  - BACKGROUND: BK and JC polyomaviruses encode microRNAs which may facilitate the
      establishment of persistent infection. MicroRNAs contribute to disease
      pathogenesis, and may provide useful tools in laboratory diagnostics and patient
      management. OBJECTIVES: In this pilot work we studied whether viral and cellular
      microRNAs can be extracted and detected from body fluids to provide added value
      in a diagnostic laboratory. STUDY DESIGN: Altogether 120 human plasma, urine, and
      cerebrospinal fluid samples from individuals diagnosed with, or suspected of, a
      severe polyomavirus associated disease, were included in the study. The samples
      were spiked with unrelated synthetic microRNA to control for sample quality and
      inhibition. BKV specific bkv-miR-B1-5p, JCV specific jcv-miR-J1-5p, and bkv-miR
      B1-3p/jcv-miR-J1-3p, sharing identical sequences between the two viruses, were
      amplified from human samples using specific TaqMan assays. Expression of 84
      circulating human microRNAs was studied in four selected plasma samples in
      microarray. RESULTS: jcv-miR-J1-5p and bkv-miR-B1-3p/jcv-miR-J1-3p were
      frequently amplified from human plasma, urine, and cerebrospinal fluid samples.
      bkv-miR-B1-5p was amplified from one-third of the samples, which often contained
      high viral DNA loads. A microarray screen of human microRNAs in plasma samples
      suggested regulation of several human microRNA expression in BKV positive vs
      negative samples. CONCLUSIONS: Viral and cellular microRNAs can be processed and
      detected from human body fluids. They may prove useful in the diagnosis and
      management of severe polyomavirus associated diseases, calling for further
      clinical evaluation.

PMID- 25766979
TI  - Nucleic acid testing by public health referral laboratories for public health
      laboratories using the U.S. HIV diagnostic testing algorithm.
AB  - BACKGROUND: Many public health laboratories adopting the U.S. HIV laboratory
      testing algorithm do not have a nucleic acid test (NAT), which is needed when the
      third- or fourth-generation HIV screening immunoassay is reactive and the
      antibody-based supplemental test is non-reactive or indeterminate. OBJECTIVES:
      Among public health laboratories utilizing public health referral laboratories
      for NAT conducted as part of the algorithm, we evaluated the percentage of
      screening immunoassays needing NAT, the number of specimens not meeting APTIMA
      (NAT) specifications, time to APTIMA result, the proportion of acute infections
      (i.e., reactive APTIMA) among total infections, and screening immunoassay
      specificity. STUDY DESIGN: From August 2012 to April 2013, 22 laboratories
      enrolled to receive free APTIMA (NAT) at New York or Florida public health
      referral laboratories. Data were analyzed for testing conducted until June 2013.
      RESULTS: Submitting laboratories conducted a median of 4778 screening
      immunoassays; 0-1.3% (median 0.2%) needed NAT. Of 140 specimens received, 9
      (6.4%) did not meet NAT specifications. The median time from specimen collection
      to reporting the 11 reactive NAT results was ten days, including six days from
      receipt in the submitting laboratory to shipment to the referral laboratory.
      Acute infections ranged from 0 to 12.5% (median 0%) of total infections. Third-
      and fourth-generation immunoassays met package insert specificity values.
      CONCLUSIONS: Public health referral laboratories provide a feasible option for
      conducting NAT. Reducing the time from specimen collection to submission of
      specimens for NAT is an important step toward maximizing the public health impact
      of identifying acute infections.

PMID- 25766980
TI  - Clinical diagnosis of early dengue infection by novel one-step multiplex real
      time RT-PCR targeting NS1 gene.
AB  - BACKGROUND: Dengue is a mosquito-borne disease that causes a public health
      problem in tropical and subtropical countries. Current immunological diagnostics
      based on IgM and/or nonstructural protein 1 (NS1) antigen are limited for acute
      dengue infection due to low sensitivity and accuracy. OBJECTIVES: This study
      aimed to develop a one-step multiplex real-time RT-PCR assay showing higher
      sensitivity and accuracy than previous approaches. STUDY DESIGN: Serotype
      specific primers and probes were designed through the multiple alignment of NS1
      gene. The linearity and limit of detection (LOD) of the assay were determined.
      The assay was clinically validated with an evaluation panel that was
      immunologically tested by WHO and Malaysian specimens. RESULTS: The LOD of the
      assay was 3.0 log10 RNA copies for DENV-1, 2.0 for DENV-3, and 1.0 for DENV-2 and
      DENV-4. The assay showed 95.2% sensitivity (20/21) in an evaluation panel,
      whereas NS1 antigen- and anti-dengue IgM-based immunological assays exhibited 0%
      and 23.8-47.6% sensitivities, respectively. The assay showed 100% sensitivity
      both in NS1 antigen- and anti-dengue IgM-positive Malaysian specimens (26/26).
      The assay provided the information of viral loads and serotype with
      discrimination of heterotypic mixed infection. CONCLUSIONS: The assay could be
      clinically applied to early dengue diagnosis, especially during the first 5 days
      of illness and approximately 14 days after infection showing an anti-dengue IgM
      positive response.

PMID- 25766981
TI  - An atypical course of coxsackievirus A6 associated hand, foot and mouth disease
      in extremely low birth weight preterm twins.
AB  - The incidence of coxsackievirus A6 (CV-A6) associated hand, foot and mouth
      disease (HFMD) has reportedly increased since 2008 with sometimes severe
      complications. We here describe an atypical course of CV-A6-associated HFMD in
      extremely low birth weight twins. The CV-A6-strains are genetically closely
      related to international strains isolated from HFMD outbreaks. 

PMID- 25766982
TI  - Absence of novel human parvovirus (PARV4) in Danish mothers and children.
AB  - BACKGROUND: The recently discovered human parvovirus 4 (PARV4) is found most
      frequently in injection drug users, HIV-positive patients, and in haemophiliacs.
      Studies from Ghana report the finding of PARV4 in plasma from 2 to 12% of
      children without acute infection, and in nasal secretions and faecal samples.
      Studies of PARV4 in children from industrialized countries are few. OBJECTIVES:
      We aimed to describe the occurrence of PARV4 in a population-based birth cohort
      of 228 Danish mothers and their healthy children who previously participated in a
      study of respiratory tract infections in infancy. STUDY DESIGN: Children were
      included over a whole calendar year and were monitored through monthly home
      visits through the first year of life. Plasma samples for the present study were
      available from 228 mothers, 176 newborns, and 202 12-months-old children. All
      samples were analysed for the presence of PARV4 antibodies by enzyme immunoassay,
      and samples with detectable antibodies were in addition studied by real-time PCR.
      RESULTS: One (0.4%) of 228 mothers had PARV4 IgG exceeding the cut-off absorbance
      level and another had borderline IgG reactivity. No mother among these two had an
      acute infection, as they were IgM and PARV4 DNA negative. All blood samples from
      newborns and one-year-old children had IgG and IgM reactivity below cut-off.
      CONCLUSIONS: PARV4 is rare in Danish mothers and infants. Further studies are
      needed, in both rural and urban settings, to investigate the epidemiology and
      clinical significance of this novel human parvovirus.

PMID- 25766983
TI  - Molecular characterization of respiratory syncytial viruses infecting children
      reported to have received palivizumab immunoprophylaxis.
AB  - BACKGROUND: Respiratory syncytial virus (RSV) is a major cause of respiratory
      infections in children. Palivizumab (PZ) is the only RSV-specific
      immunoprophylaxis approved by the U.S. Food and Drug Administration. Mutations
      leading to amino acid substitutions in the PZ binding site of the RSV F protein
      have been associated with breakthrough RSV infections in patients receiving PZ.
      OBJECTIVE: To detect PZ resistance conferring mutations in RSV strains from
      children who received PZ. STUDY DESIGN: Children aged <= 24 months on October 31
      who were hospitalized or had outpatient visits for respiratory illness and/or
      fever during October-May 2001-2008 in 3 US counties were included. PZ receipt was
      obtained from parent interviews and medical records among children subsequently
      infected with RSV. Archived nasal/throat swab specimens were tested for RSV by
      real-time RT-PCR. The coding region of the PZ binding site of the RSV F protein
      was sequenced using both Sanger and pyrosequencing methods. RESULTS: Of 8762
      enrolled children, 375 (4.3%) were tested for RSV and had a history of PZ
      receipt, of which 56 (14.9%) were RSV-positive and 45 of these had available
      archived specimens. Molecular typing identified 42 partial F gene sequences in
      specimens from 39 children: 19 single RSV subgroup A, 17 subgroup B and 3 mixed
      infections. Nucleotide substitutions were identified in 12/42 (28.6%) RSV
      strains. PZ resistance mutations were identified in 4 (10.2%) of the 39 children,
      of which one had documented PZ receipt. CONCLUSIONS: Although RSV PZ resistance
      mutations were infrequent, most RSV-associated illnesses in children with a
      history of PZ receipt were not due to strain resistance.

PMID- 25766984
TI  - A single chimpanzee-human neutralizing monoclonal antibody provides post-exposure
      protection against type 1 and type 2 polioviruses.
AB  - BACKGROUND: Development of anti-poliovirus therapies to complement vaccination is
      an urgent priority. A number of antiviral drugs are in development. Recently we
      have developed human monoclonal antibodies that could be used for treatment of
      chronically infected individuals and emergency response to potential reappearance
      of polioviruses after eradication. OBJECTIVE: The aim of this study was to
      characterize neutralizing activity of anti-poliovirus monoclonal antibody A12
      against wild type, vaccine-derived, and drug-resistant poliovirus strains,
      evaluate in vivo pre- and post-exposure protective properties of the antibody
      against polioviruses of serotypes 1 and 2, and to determine whether it interferes
      with response to immunization with poliovirus vaccine. STUDY DESIGN:
      Immunogenicity studies were performed in CD1 mice. Poliovirus neutralizing titers
      were determined in poliovirus microneutralization assay. Poliovirus immunization
      challenge experiments were performed in poliovirus-susceptible TgPVR21 mice.
      RESULTS: We show that monoclonal antibody A12 effectively neutralizes in vitro a
      broad range of type 1 and type 2 wild and vaccine-derived polioviruses, provides
      effective pre- and post-exposure protection of TgPVR21 mice from challenge with a
      lethal dose of poliovirus. Treatment of animals with the antibody concurrent with
      IPV immunization does not prevent immune response to the vaccine. CONCLUSIONS:
      Anti-poliovirus antibody A12 effectively neutralizes a range of wild and VDPV
      strains and protectstransgenic mice susceptible to poliovirus against lethal
      challenge upon pre- and post-exposure administration. This suggests that the
      antibodies could be used in combination with drugs and/or vaccine to improve
      their efficacy and prevent emergence of resistant variants, and provides a
      justification for initiating their clinical evaluation.

PMID- 25766985
TI  - A simple method to elute cell-free HIV from dried blood spots improves their
      usefulness for monitoring therapy.
AB  - BACKGROUND: Dried blood spots (DBS) improve access to HIV viral load (VL)
      testing, but yield increased VL measurements compared to the plasma reference
      method because of cell-associated viral nucleic acid. In clinical settings, DBS
      methods may falsely categorize many patients as failing therapy. OBJECTIVES:
      Description of a simple method, free virus elution (FVE), to preferentially elute
      plasma-associated virus from DBS samples with phosphate-buffered saline, and an
      initial HIV VL performance comparison with standard DBS elution methods. STUDY
      DESIGN: The mechanism of action of FVE was studied with model DBS samples
      containing purified virus or washed HIV-containing cells, and with a DNA-specific
      HIV PCR. Using clinical samples, VL results from the new FVE method were compared
      to results from a dried fluid spot procedure (DFSP) protocol, which uses a
      guanidinium-based elution method, using plasma VL as the reference method.
      RESULTS: Model system experiments suggest that the method efficiently separates
      virus from cell-associated HIV, with a wide tolerance for incubation time and
      temperature. In 196 clinical samples, FVE reduced VL over-quantification from
      DBS, and improved DBS clinical concordance with plasma from 67% to 95%.
      CONCLUSIONS: A simple elution in PBS significantly reduced the over
      quantification of HIV VL in DBS. Additional studies are needed to validate the
      method in fingerstick-collected specimens and to further understand the
      compartmentalization of HIV DNA and RNA in DBS specimens.

PMID- 25766986
TI  - Viral load in children with congenital cytomegalovirus infection identified on
      newborn hearing screening.
AB  - BACKGROUND: Congenital cytomegalovirus (CMV) infection is the most common non
      genetic cause of sensorineural hearing loss (SNHL) in children. However,
      congenital SNHL without other clinical abnormalities is rarely diagnosed as CMV
      related in early infancy. OBJECTIVES: The aim of this study was to identify and
      treat patients with congenital CMV-related SNHL or CMV-related clinical
      abnormalities other than SNHL. The association between CMV load and SNHL was also
      evaluated. STUDY DESIGN: Newborns who had abnormal hearing screening results or
      other clinical abnormalities were screened for congenital CMV infection by PCR of
      saliva or urine specimens, and identified infected patients were treated with
      valganciclovir (VGCV) for 6 weeks. The CMV load of patients with or without SNHL
      was compared at regular intervals during as well as after VGCV treatment.
      RESULTS: Of 127 infants with abnormal hearing screening results, and 31 infants
      with other clinical abnormalities, CMV infection was identified in 6 and 3
      infants, respectively. After VGCV treatment, 1 case had improved hearing but the
      other 5 SNHL cases had little or no improvement. Among these 9 patients with or
      without SNHL at 1 year of age, there was no significant difference in CMV blood
      or urine load at diagnosis, but both were significantly higher in patients with
      SNHL during VGCV treatment. CONCLUSIONS: Selective CMV screening of newborns
      having an abnormal hearing screening result would be a reasonable strategy for
      identification of symptomatic congenital CMV infection. Prolonged detection of
      CMV in blood could be a risk factor for SNHL.

PMID- 25766987
TI  - Relationship of herpes simplex encephalitis and transcranial direct current
      stimulation--a case report.
AB  - We report a rare case of relapsing herpes simplex encephalitis in a-37-year-old
      patient which was previously confirmed by positive polymerase chain reaction,
      herpes simplex virus (HSV) type1 IgG antibodies in cerebrospinal fluid and
      characterized on MRI. During the first admission, he was treated with continuous
      acyclovir treatment for one month with clinical improvement except for residual
      aphasia, for which he received a course of outpatient transcranial direct current
      stimulation (tDCS). A constant current of 1.2 mA was applied for 20 min twice
      daily. After the 4th day the patient was found to be irritable and uncooperative
      by staff and family members. A subsequent MRI showed significant deterioration of
      the lesion on comparison to the first MRI which led to discontinuation of
      tDCS.The relatively rapid exacerbation of HSV in only a few days is unusual. Our
      aim is to discuss if tDCS is related to HSV relapse and in doing so highlight
      possible mechanisms.

PMID- 25766989
TI  - HCV RNA measurement in samples with diverse genotypes using versions 1 and 2 of
      the Roche COBAS(r) AmpliPrep/COBAS(r) TaqMan(r) HCV test.
AB  - BACKGROUND: Accurate HCV RNA measurement is required for monitoring treatment.
      Underquantification has been reported with some genotypes, particularly genotype
      4, using version 1 of the Roche COBAS((r)) AmpliPrep/COBAS((r)) TaqMan((r)) HCV
      Test. OBJECTIVES: Compare the viral loads of clinical specimens representing
      diverse genotypes from across the United States using versions 1 (V1) and 2 (V2)
      of the Roche COBAS((r)) AmpliPrep/COBAS((r)) TaqMan((r)) HCV Test. Assess the
      frequency of nt145 and nt165 variants in the 5' UTR associated with detection
      failures and underquantification in a large clinical sample database. STUDY
      DESIGN: Three hundred archived clinical samples were measured using V1 and V2.
      Bland-Altman analysis was performed on log-transformed results and compared by
      genotype. The frequencies of nt145 and nt165 variants from 15,817 sequences were
      calculated. RESULTS: On average, V2 results were 0.16 logIU/mL lower than V1
      results. The average genotype 4 sample was 0.08 logIU/mL higher in V1 than V2.
      The largest individual sample differences were -2.10 (genotype 2b) and 1.57
      (genotype 2a) logIU/mL. For genotype 4 samples, the greatest underquantification
      by V1 was 1.46 logIU/mL. There were 13 (0.082%) variants at nt145 and 24 variants
      at nt165 (0.152%), including one sequence with variants at both positions
      (0.0063%). CONCLUSIONS: Genotype 4 samples from the U.S. are rarely
      underquantified and not disproportionately so compared to other genotypes using
      the COBAS((r)) AmpliPrep/COBAS((r)) TaqMan((r)) HCV Tests. Variants at the nt145
      and nt165 positions are uncommon in the U.S. and double variants are exceedingly
      rare. Underquantification of HCV samples with the V1 assay is likely a very rare
      occurrence in U.S.

PMID- 25766988
TI  - Prevalence of HCV NS3 pre-treatment resistance associated amino acid variants
      within a Scottish cohort.
AB  - BACKGROUND: Protease inhibitors (PI) including boceprevir, telaprevir and
      simeprevir have revolutionised HCV genotype 1 treatment since their introduction.
      A number of pre-treatment resistance associated amino acid variants (RAVs) and
      polymorphisms have been associated with reduced response to treatment.
      OBJECTIVES: We measured the prevalence of RAVs/polymorphisms in a PI treatment
      naive HCV genotype 1 Scottish cohort using Sanger sequencing. STUDY DESIGN:
      Chronically infected, treatment-naive, HCV genotype 1 patients (n = 146)
      attending NHS Greater Glasgow and Clyde clinics were investigated for
      RAVs/polymorphisms to the PIs boceprevir, telaprevir and simeprevir. The NS3/4A
      region was amplified by nested polymerase chain reaction. The 1.4 kb amplified
      product was sequenced using an ABI 3710XL DNA sequencer. Sequence analysis was
      performed using web-based ReCall (beta 2.10). Amino acid positions 36, 41, 43,
      54, 55, 80, 109, 122, 155, 156, 168 and 170 were analysed for RAVs/polymorphisms.
      RESULTS: Overall, 23.29% (34/146) of patients had an RAV or polymorphism
      detected. Overall, 13.69% (20/146) of patients had HCV virus that contained the
      Q8 K polymorphism. Other RAVs detected were: V36 M 0.70% (1/146), V36L 0.70%
      (1/146), T54S 6.85% (10/146), V55A 3.42% (5/146) and V/I170A 0.68% (1/146). Four
      patients had dual combinations of mutations (T54S+V36L; T54S+V55A and 2 patients
      with T54S+Q80K). CONCLUSIONS: Q80K was the most prevalent baseline polymorphism
      detected in the Scottish cohort. Simeprevir treatment is not recommended in
      patients infected with the Q80K genotype 1a variant. This highlights the need for
      baseline sequencing prior to administration of this drug in this population.

PMID- 25766990
TI  - Novel reassortant H10N7 avian influenza viruses isolated from chickens in Eastern
      China.
AB  - BACKGROUND: Since 2004, the H10N7 subtype avian influenza virus (AIV) has caused
      sporadic human infections with variable clinical symptoms world-wide. However,
      there is limited information pertaining to the molecular characteristics of H10N7
      AIVs in China. OBJECTIVE: To more fully characterize the genetic relationships
      between three novel H10N7 strains isolated from chickens in Eastern China and the
      strains isolated from birds throughout Asia, and to determine the pathogenicity
      of the H10N7 isolates in vivo. STUDY DESIGN: All eight gene segments from the
      Chinese H10N7 strains were sequenced and compared with AIV strains available in
      GenBank. The virulence of the three isolates was determined in chickens and mice.
      RESULTS: Three H10N7 subtype avian influenza viruses were isolated from chickens
      in live poultry markets in Eastern China in 2014: (1)
      A/chicken/Zhejiang/2C66/2014(H10N7) (ZJ-2C66), (2)
      A/chicken/Zhejiang/2CP2/2014(H10N7) (ZJ-2CP2), and (3)
      A/chicken/Zhejiang/2CP8/2014(H10N7) (ZJ-2CP8). Phylogenetic analysis indicated
      that the viruses contained genetic material from H10, H2, H7, and H3 AIV strains
      that were circulating at the same time. The reassortant H10N7 viruses were found
      to be minimally pathogenic in chickens and moderately pathogenic in mice. The
      viruses were able to replicate in mice without prior adaptation. CONCLUSION:
      These results suggest that H10N7 surveillance in poultry should be used as an
      early warning system for avian influenza outbreaks. The novel strains identified
      here may post a threat to human health in the future if they continue to
      circulate.

PMID- 25766991
TI  - TLR3 polymorphisms are associated with virologic response to hepatitis C virus
      (HCV) treatment in HIV/HCV coinfected patients.
AB  - BACKGROUND: Toll-like receptor-3 (TLR3) is a cellular receptor that may recognize
      double-stranded RNA (dsRNA) from viruses, resulting in production of
      proinflammatory cytokines and interferons, which are important for the adaptive
      immune response. OBJECTIVES: To analyze the association between Toll-like
      receptor-3 (TLR3) polymorphisms (rs3775291 and rs13126816) and virologic response
      to pegylated interferon-alpha plus ribavirin (pegIFNalpha/RBV) therapy in HIV/HCV
      coinfected patients. STUDY DESIGN: We performed a retrospective study in 321
      naive patients treated with pegIFNalpha/RBV. Genotyping was performed by using
      the GoldenGate((r)) assay with VeraCode((r)). The outcome variables were early
      virologic response (EVR) and sustained virologic response (SVR). RESULTS: In a
      multivariate analysis, rs3775291 A allele decreased the likelihood of achieving
      EVR (aOR = 0.20; p = 0.018) and SVR (aOR = 0.38; p = 0.024). Regarding
      rs13126816, the percentage of EVR decreased with each minor A allele (p = 0.034)
      in HCV-GT2/3 patients, although no significant association was obtained in the
      multivariate analysis (p = 0.076). Regarding TLR3 haplotypes (comprised of
      rs3775291 and rs13126816), GT2/3 patients with AA haplotype had decreased odds of
      achieving EVR (p = 0.030), whereas GG haplotype increased the likelihood (p =
      0.018). Regarding SVR, GG haplotype carriers had increased odds of achieving SVR
      (p = 0.019, p = 0.043 and p = 0.070 for all, GT2/3 and GT1/4 patients,
      respectively). Besides, GT1/4 patients with GA haplotype had lower odds of
      achieving SVR (p = 0.039). CONCLUSIONS: Our study shows the first evidence that
      two TLR3 polymorphisms (rs3775291 and rs13126816) seem to be related to the HCV
      therapy response in HCV/HIV coinfected patients.

PMID- 25766992
TI  - Effects of sequence alterations on results from genotypic tropism testing.
AB  - BACKGROUND: geno2pheno[coreceptor] is a bioinformatic method for genotypic
      tropism determination (GTD) which has been extensively validated. OBJECTIVES: GTD
      can be affected by sequencing/base-calling variability and unreliable
      representation of minority populations in Sanger bulk sequencing. This study aims
      at quantifying the robustness of geno2pheno[coreceptor] with respect to these
      issues. GTD with a single amplification or in triplicate (henceforth
      singleton/triplicate) is considered. STUDY DESIGN: From a dataset containing
      67,997HIV-1 V3 nucleotide sequences, two datasets simulating sequencing
      variability were created. Further two datasets were created to simulate
      unreliable representation of minority variants. After interpretation of all
      sequences with geno2pheno[coreceptor], probabilities of change of predicted
      tropism were calculated. RESULTS: geno2pheno[coreceptor] tends to report reduced
      false-positive rates (FPRs) when sequence alterations are present. Triplicate
      FPRs tend to be lower than singleton FPRs, resulting in a bias towards
      classifying viruses as X4-capable. Alterations introduced into nucleotide
      sequences by simulation change singleton predicted tropism with a probability <=
      2%. Triplicate prediction lowers this probability for predicted X4 tropism, but
      raises it for predicted R5 tropism <= 6%. Simulated limited detection of minority
      variants in X4 sequences resulted in unchanged predicted tropism with probability
      above 90% as compared to probability above 98% with triplicate FPRs. CONCLUSIONS:
      geno2pheno[coreceptor] proved to be robust when sequence alterations are present
      and when detectable minorities are missed by bulk sequencing. Changes in tropism
      prediction due to sequence alterations as well as triplicate prediction are much
      more likely to result in false X4-capable predictions than in false R5
      predictions.

PMID- 25766993
TI  - The evaluation method for assessing a diagnostic test of HIV: some noteworthy
      issues.

PMID- 25766994
TI  - Seroprevalence of trichodysplasia spinulosa-associated polyomavirus in Japan.
AB  - BACKGROUND: Trichodysplasia spinulosa-associated polyomavirus (TSV) was
      identified in, and shown to be the probable cause of, trichodysplasia spinulosa,
      a rare skin disease. To date, serological analyses have revealed that TSV
      infection is common among adults in the general population of Europe and
      Australia. However, there have been no reports of TSV in Asia. OBJECTIVE: To
      study the prevalence of TSV infection in Japan. STUDY DESIGN: TSV-VP1 expressed
      in a recombinant baculovirus expression system in an insect cell line, Tn5, self
      assembled into virus-like particles. Overall, 1000 serum samples were examined by
      enzyme-linked immunosorbent assays using virus-like particles of TSV as antigen.
      Participants ranged in age from 0 to 94 years. RESULTS: Overall, 629 of 1000
      serum samples (62.9%) were positive for anti-TSV antibodies. The seropositive
      rate increased with age and the seroprevalence of TSV significantly increased
      from 17.1% (25/146) in children aged from 0 to 4 years to 78.7% (472/600) in
      adults aged over 20 years (odds ratio = 0.056, 95% confidence interval = 0.035
      0.900, P = 0.000, Chi-squared test). TSV seropositivity was not different between
      sera obtained in 1980 and 2012, and was not associated with sex. Competitive
      assay demonstrated that TSV antibodies did not cross-react with BK virus or
      Merkel cell polyomavirus. CONCLUSIONS: These results provide evidence that TSV
      circulates widely in the Japanese population, with primary exposure occurring
      mainly at early childhood, similar to that previously reported in other
      countries.

PMID- 25766995
TI  - Head-to-head comparison of the diagnostic accuracies of BD VeritorTM System RSV
      and Quidel(r) Sofia(r) RSV FIA systems for respiratory syncytial virus (RSV)
      diagnosis.
AB  - BACKGROUND: Respiratory syncytial virus (RSV) is one of the most common causes of
      severe lower respiratory tract disease among infants and young children. BD
      VeritorTM System RSV (BD) and Quidel((r)) Sofia((r)) RSV FIA (QD) are the new
      generation lateral flow digital immunoassay (DIA) tests with an instrumented read
      for the qualitative detection of RSV viral antigens. OBJECTIVE: To compare the
      diagnostic accuracies of BD and QD for RSV detection using fresh nasopharyngeal
      aspirates and nasopharyngeal swab specimens collected in universal transport
      media during 2013-2014 respiratory season. STUDY DESIGN: The two DIA tests were
      performed simultaneously on randomly selected specimens on a weekly basis during
      the RSV season until 200 fresh remnant specimens were enrolled. Real-time RT-PCR
      assay results were used to compare and evaluate the performance of both RSV DIA
      assays. RESULTS: Among 200 specimens tested, RSV real-time RT-PCR assay detected
      RSV in 104 samples, while QD detected 84 samples and BD detected 74 samples as
      positive. The overall sensitivity for detection of RSV in comparison to PCR was
      71.15% (61.3-79.4) for BD and 80.77% (71.6-87.6) for QD system (P=0.36). The
      specificity was 100% (95.2-100) for both systems. The work flow analysis revealed
      that the overall specimen processing time was significantly lower for BD as
      compared with the QD assay. CONCLUSIONS: In comparison with the real-time PCR,
      the QD system showed a higher sensitivity than that of the BD system, but the
      difference did not reach statistical significance (P=0.36). Both BD and QD
      systems were found comparable in terms of specificity.

PMID- 25766996
TI  - Circulating cytomegalic cells in a patient with advanced HIV presenting with
      cytomegalovirus rhinosinusitis.
AB  - We report a patient with newly diagnosed late-stage HIV presenting with fever,
      rhinosinusitis and cognitive impairment. Analysis of cerebrospinal fluid and
      nasal turbinate tissue confirmed cytomegalovirus (CMV) infection. CMV pp65
      antigen assay conducted on peripheral blood leukocytes revealed large CMV
      infected mononuclear cells (diameter ~ 50 MUm) with an unusual cytoplasmic
      pattern of pp65 staining. These large cells were also seen in buffy coat Wright's
      stained smears; their size, morphology and pp65 antigen uptake pattern were
      consistent with CMV infected cytomegalic endothelial cells. While CMV sinus
      infections are occasionally encountered in AIDS patients, this is the first
      report to document CMV infection of the nasal mucosa with secondary sinusitis and
      chronic suppurative otitis media. Furthermore, the detection of circulating
      cytomegalic cells is described--a rare finding with pathological and clinical
      significance in immunocompromised patients with CMV disease.

PMID- 25766997
TI  - A ruthenium-based biomimetic hydrogen cluster for efficient photocatalytic
      hydrogen generation from formic acid.
AB  - A ruthenium-based biomimetic hydrogen cluster, [Ru2 (CO)6 (MU-SCH2 CH2 CH2 S)]
      (1), has been synthesized and, in the presence of the P ligand tri(o
      tolyl)phosphine, demonstrated efficient photocatalytic hydrogen generation from
      formic acid decomposition. Turnover frequencies (TOFs) of 5500 h(-1) and turnover
      numbers (TONs) over 24 700 were obtained with less than 50 ppm of the catalyst,
      thus representing the highest TOFs for ruthenium complexes as well as the best
      efficiency for photocatalytic hydrogen production from formic acid. Moreover, 1
      showed high stability with no significant degradation of the photocatalyst
      observed after prolonged photoirradiation at 90  degrees C.

PMID- 25766998
TI  - Initial stages of oxide formation on the Zr surface at low oxygen pressure: An in
      situ FIM and XPS study.
AB  - An improved methodology of the Zr specimen preparation was developed which allows
      fabrication of stable Zr nanotips suitable for FIM and AP applications. Initial
      oxidation of the Zr surface was studied on a Zr nanotip by FIM and on a
      polycrystalline Zr foil by XPS, both at low oxygen pressure (10(-8)-10(-7)mbar).
      The XPS data reveal that in a first, fast stage of oxidation, a Zr suboxide
      interlayer is formed which contains three suboxide components (Zr(+1), Zr(+2) and
      Zr(+3)) and is located between the Zr surface and a stoichiometric ZrO2 overlayer
      that grows in a second, slow oxidation stage. The sole suboxide layer has been
      observed for the first time at very early states of the oxidation (oxygen
      exposure <= 4L). The Ne(+) FIM observations are in accord with a two stage
      process of Zr oxide formation.

PMID- 25766999
TI  - The relationship between grain boundary structure, defect mobility, and grain
      boundary sink efficiency.
AB  - Nanocrystalline materials have received great attention due to their potential
      for improved functionality and have been proposed for extreme environments where
      the interfaces are expected to promote radiation tolerance. However, the precise
      role of the interfaces in modifying defect behavior is unclear. Using long-time
      simulations methods, we determine the mobility of defects and defect clusters at
      grain boundaries in Cu. We find that mobilities vary significantly with boundary
      structure and cluster size, with larger clusters exhibiting reduced mobility, and
      that interface sink efficiency depends on the kinetics of defects within the
      interface via the in-boundary annihilation rate of defects. Thus, sink efficiency
      is a strong function of defect mobility, which depends on boundary structure, a
      property that evolves with time. Further, defect mobility at boundaries can be
      slower than in the bulk, which has general implications for the properties of
      polycrystalline materials. Finally, we correlate defect energetics with the
      volumes of atomic sites at the boundary. 

PMID- 25767000
TI  - [Hemoperitoneum: A rare complication after diagnostic colonoscopy].

PMID- 25767001
TI  - [Psychoneuroimmunology in irritable bowel syndrome].

PMID- 25767002
TI  - [Terminology changes in serum tumor markers].

PMID- 25767003
TI  - [Peritoneal mesothelioma unmasked by an acute appendicitis].

PMID- 25767004
TI  - Noninvasive prenatal diagnosis of Huntington disease: detection of the paternally
      inherited expanded CAG repeat in maternal plasma.
AB  - OBJECTIVE: With a shift towards noninvasive testing, we have explored and
      validated the use of noninvasive prenatal diagnosis (NIPD) for Huntington disease
      (HD). METHODS: Fifteen couples have been included, assessing a total of n = 20
      pregnancies. Fetal paternally inherited CAG repeat length was determined in total
      cell-free DNA from maternal plasma using a direct approach by PCR and subsequent
      fragment analysis. RESULTS: All fetal HD (n = 7) and intermediate (n = 3) CAG
      repeats could be detected in maternal plasma. Detection of repeats in the normal
      range (n = 10) was successful in n = 5 cases where the paternal repeat size could
      be distinguished from maternal repeat patterns after fragment analysis. In all
      other cases (n = 5), the paternal peaks coincided with the maternal peak pattern.
      All NIPD results were concordant with results from routine diagnostics on fetal
      genomic DNA from chorionic villi. CONCLUSION: In this validation study, we
      demonstrated that all fetuses at risk for HD could be identified noninvasively in
      maternal plasma. Additionally, we have confirmed results from previously
      described case reports that NIPD for HD can be performed using a direct approach
      by PCR. For future diagnostics, parental CAG profiles can be used to predict the
      success rate for NIPD prior to testing.

PMID- 25767005
TI  - A case of rectal carcinoma with skin and bone marrow metastasis with concurrent
      extensive visceral involvement; unusual and dismal co-incidence.
AB  - Novel systemic therapies and modern surgical and ablative approaches have
      improved the survival rates for the patients with metastatic colorectal cancer.
      However, there are still patients with poor prognosis and underlying mechanisms
      that could not be defined clearly. Metastatic colorectal cancer patients with
      skin metastasis have a poor prognosis. A 45-year-old man, who presented with
      large bowel obstruction, was diagnosed with metastatic rectal adenocarcinoma.
      Unresectable liver metastases were found at diagnosis. FOLFOX plus bevacizumab
      treatment was started, but the patient developed bowel obstruction after the
      third cycle. Therefore, ileostomy was performed. Multiple skin, lung, liver and
      bone metastases appeared during that time. Bone marrow biopsy demonstrated
      diffuse infiltration by adenocarcinoma cells. Even though partial remission was
      achieved after 4 cycles of FOLFIRI-cetuximab, the disease progressed after the
      8th cycle. The patient lost his life due to disease progression 8 months after
      the diagnosis. Bone marrow and skin are unusual sites of metastasis for
      colorectal carcinoma. Metastases in bone marrow and skin develop at later stages
      of metastatic disease. This patient lived only 4 months after the development of
      skin and bone marrow metastases. Skin and bone marrow metastases may be the
      harbingers of short survival. Biopsy of metastatic sites is crucial for diagnosis
      and detailed molecular analysis. Molecular pathway alterations underlying worse
      disease course may be found, and hence probable targets for drug improvement may
      be indicated. 

PMID- 25767006
TI  - Management of acute chest pain: A major role for coronary CT angiography.
AB  - Most patients presenting with acute chest pain (ACP) at the emergency unit do not
      have any marked electrocardiogram abnormalities or known history of heart
      disease. Identifying the few patients who have, or will actually develop acute
      coronary syndrome in this group that is considered to be at low risk, is an
      actual clinical challenge for emergency department physicians. In these patients,
      the goal of complementary non-invasive morphological or functional imaging tests
      is to exclude heart disease. The diagnostic values of coronary CT angiography
      include a sensitivity of 96% and a negative likelihood ratio of 0.09, which are
      highly contributory to the diagnosis, and the integration of this imaging test
      into a decision tree algorithm appears to be the least expensive strategy with
      the best cost/effective ratio. Coronary CT angiography is indicated in the
      presence of ACP associated with an inconclusive electrocardiogram, in the absence
      of any other obvious diagnoses, when the ultrasensitive troponin assay is
      negative or the dynamic changes are modest, slow and/or inconclusive. Ideally,
      coronary CT angiography should be performed within 3 to 48hours after the initial
      consultation. 

PMID- 25767007
TI  - About the article: Effect of combined aerobic and resistance training versus
      aerobic training on arterial stiffness.

PMID- 25767008
TI  - Thoracic aortic dissection and rupture in conotruncal cardiac defects: A
      population-based study.
AB  - BACKGROUND: Although the risk of thoracic aortic dissection and rupture (TAD) is
      well-known in bicuspid aortic valve (BAV), the risk of TAD in other congenital
      heart diseases (CHD), particularly conotruncal lesions like tetralogy of Fallot
      (TOF), truncus arteriosus, D-transposition of the great arteries (D-TGA), and
      double outlet right ventricle is currently unknown. The primary purpose of this
      study was to describe TAD in conotruncal CHD, and the secondary purpose was to
      explore whether an association exists between TAD and conotruncal CHD. METHODS
      AND RESULTS: Using the Texas Inpatient Public Use Data File, an administrative
      database of all Texas hospitalizations, including >37.9 million hospitalizations
      from January 1999 through June 2012, 12,016 cases of TAD and 214 cases of TAD in
      CHD were identified. The most common lesions were BAV (42%), atrial septal defect
      (21%), aortic coarctation (7%), ventricular septal defect (6%), and patent ductus
      arteriosus (4%). Three patients with TOF, 2 with D-TGA, and 1 with truncus
      arteriosus were admitted with TAD. An exploratory case-control study in patients
      older than 1 year using multilevel logistic regression models to evaluate the
      association between CHD and TAD that controlled for known TAD risk factors
      demonstrated a significant association between TAD and BAV (OR 10, 95% CI 8.2-13)
      but not coarctation of the aorta or any conotruncal lesion. CONCLUSIONS: TAD in
      conotruncal CHD is exquisitely rare. In our hospitalized population, there was no
      increased occurrence of TAD in conotruncal CHD above what would be expected in
      the rest of the hospitalized population.

PMID- 25767009
TI  - Beta blocker for patients with pulmonary arterial hypertension: A single center
      experience.

PMID- 25767010
TI  - Five-year clinical outcomes in patients with significant coronary artery spasm: A
      propensity score-matched analysis.
AB  - BACKGROUND: Coronary artery spasm (CAS) is known to be a risk factor of acute
      coronary syndrome and angina pectoris. However, there is no currently available
      data with larger study population regarding long-term clinical outcomes of CAS in
      real world clinical practice. OBJECTIVES: We evaluated the prevalence of CAS and
      the impact of CAS on 5-year clinical outcomes in a series of Asian CAS patients
      documented by intracoronary acetylcholine (Ach) provocation test. METHODS: A
      total of 1413 consecutive patients without significant coronary artery disease
      (CAD) who underwent Ach provocation test between Nov. 2004 and Oct. 2008 were
      enrolled. Significant CAS was defined as >70% of narrowing by incremental
      intracoronary injection of 20, 50 and 100 MUg. Patients were divided into two
      groups based on the presence of significant CAS (the non-CAS group: n=640, the
      CAS group; n=773). To adjust potential confounders, a propensity score matched
      (PSM) analysis was performed using the logistic regression model. RESULTS: A
      total of 54.7% (773/1413) patients were diagnosed as CAS documented by Ach
      provocation test. After PSM analysis, 2 propensity-matched groups (451 pairs,
      n=902, C-statistic=0.677) were generated. Despite of similar incidence of
      individual hard endpoints including mortality, myocardial infarction and
      revascularization, the CAS group showed the higher trend of recurrent angina
      requiring follow up angiography than the non-CAS group up to 5 years (HR; 1.56,
      95% C.I.; 0.99-2.46, p=0.054). CONCLUSIONS: The prevalence of CAS was 54.7%.
      Although the cumulative incidence of recurrent angina requiring follow up
      coronary angiography seems to be increased up to 5 years in CAS patients, CAS
      patients was not associated with major individual and composite clinical outcomes
      such as mortality, MI, PCI, CVA with optimal medical therapy as compared with
      patients without CAS.

PMID- 25767011
TI  - High CHA2DS2-VASc score predicts left atrial thrombus or spontaneous echo
      contrast detected by transesophageal echocardiography.

PMID- 25767012
TI  - Risk of myocardial infarction in trials with Dipeptidyl Peptidase-4 inhibitors:
      Is duration of study a real issue?

PMID- 25767013
TI  - Can thyroid break your heart? Role of thyroid in Takotsubo cardiomyopathy: A
      single center retrospective study.

PMID- 25767014
TI  - Localised right precordial QRS prolongation - A novel form of calculation.

PMID- 25767015
TI  - Fatal dynamic mitral regurgitation as a presentation of benfluorex-Induced
      valvular heart toxicity.

PMID- 25767016
TI  - Palliative needs for heart failure or chronic obstructive pulmonary disease:
      Results of a multicenter observational registry.
AB  - BACKGROUND: Heart failure (HF) and chronic obstructive pulmonary disease (COPD)
      share a common organ failure trajectory marked by prognostic uncertainty, which
      is a barrier to appropriate provision of palliative care. We describe in a
      prospective cohort from specialist hospital services the epidemiology and late
      clinical course of these chronic diseases to trace criteria for transition to
      palliative care in the community. METHODS AND RESULTS: Seven centers enrolled 267
      patients with advanced HF (n=174) or COPD (n=93) using common (multiple
      hospitalizations or severely impaired functional status or cachexia) and disease
      specific (HF: systolic dysfunction, NYHA classes III-IV, end-organ hypoperfusion;
      COPD: very severe airflow obstruction, hypoxemia, hypercapnia, or long-term
      oxygen therapy) entry criteria. These patients represented 7.2% and 13%
      respectively of the overall HF and COPD population hospitalized during one year.
      They showed similar symptom burden, functional and quality of life impairment,
      recurrent hospitalizations, and 6-month mortality (39% and 37%, respectively).
      Organ failure progression was the cause of death in >75%. In-hospital overall
      stay during the previous year was the main mortality predictor in both. Disease
      specific predictors included anemia, hyponatremia, no beta-blockers in HF; older
      age, hypercapnia in COPD. CONCLUSIONS: Patients with advanced HF/COPD represent
      almost 10% of subjects hospitalized yearly with a primary diagnosis of HF or
      COPD, have similarly impaired functional status, disabling symptoms and reduced
      survival. Overall days spent in-hospital during the previous year, a "red flag"
      in the late clinical course of both diseases, might be used as a simple, reliable
      screening tool for appropriate transition to palliative care in the community.

PMID- 25767017
TI  - Selective and non-selective non-steroidal anti-inflammatory drugs differentially
      regulate pulmonary vein and atrial arrhythmogenesis.
AB  - BACKGROUND: Non-steroidal anti-inflammatory drugs (NSAIDs) increase the risk of
      atrial fibrillation (AF). This study investigated whether selective and non
      selective NSAIDs differentially regulate the arrhythmogenesis of pulmonary veins
      and atria. METHODS: Conventional microelectrodes were used to record action
      potentials (APs) in isolated rabbit PVs, sinoatrial node (SAN), left atrium (LA),
      and right atrium (RA) preparations before and after celecoxib or indomethacin
      administration. A whole-cell patch clamp was used to record the sodium-calcium
      exchanger (NCX) current, L-type calcium current (ICa-L), and late sodium current
      (INa-late) before and after celecoxib administration in isolated PV
      cardiomyocytes. RESULTS: Celecoxib (0.3, 1, and 3 MUM) reduced PV spontaneous
      beating rates, and induced delayed afterdepolarizations and burst firings in four
      of eight PV preparations (50%, p<0.05). Celecoxib also reduced SAN beating rates
      and decreased AP durations (APDs) in RA and LA, but did not change the resting
      membrane potential. Indomethacin (0.3, 1, 3, and 10 MUM) changed neither the PV
      or SAN beating rates nor RA APDs, but it reduced LA APDs. Celecoxib (3 MUM)
      significantly increased the NCX current and decreased the ICa-L, but did not
      change the INa-late. Ranolazine (10 MUM) suppressed celecoxib (3 MUM)-induced PV
      burst firings in 6 (86%, p<0.05) of 7 PVs. KB-R7943 (10 MUM) suppressed celecoxib
      (3 MUM)-induced PV burst firings in 5 (71%, p<0.05) of 7 PVs. CONCLUSIONS:
      Selective and non-selective NSAIDs differentially modulate PV and atrial
      electrophysiological characteristics. Celecoxib increased PV triggered activity
      through enhancement of the NCX current, which contributed to its
      arrhythmogenesis.

PMID- 25767018
TI  - Adaptive licensing - A way forward in the approval process of new therapeutic
      agents in Europe.

PMID- 25767019
TI  - Plant sterol supplementation on top of lipid-lowering therapies in familial
      hypercholesterolemia.

PMID- 25767020
TI  - Studies of chronic disease in Seventh-day Adventists.

PMID- 25767021
TI  - Renal denervation in resistant arterial hypertension: Effects on neurohormonal
      activation and cardiac natriuretic peptides.

PMID- 25767031
TI  - Possible mechanisms underlying slow component of VO2 on-kinetics in skeletal
      muscle.
AB  - A computer model of a skeletal muscle bioenergetic system is used to study the
      background of the slow component of oxygen consumption VO2 on-kinetics in
      skeletal muscle. Two possible mechanisms are analyzed: inhibition of ATP
      production by anaerobic glycolysis by progressive cytosol acidification (together
      with a slow decrease in ATP supply by creatine kinase) and gradual increase of
      ATP usage during exercise of constant power output. It is demonstrated that the
      former novel mechanism is potent to generate the slow component. The latter
      mechanism further increases the size of the slow component; it also moderately
      decreases metabolite stability and has a small impact on muscle pH. An increase
      in anaerobic glycolysis intensity increases the slow component, elevates cytosol
      acidification during exercise, and decreases phosphocreatine and Pi stability,
      although slightly increases ADP stability. A decrease in the P/O ratio (ATP
      molecules/O2 molecules) during exercise cannot also be excluded as a relevant
      mechanism, although this issue requires further study. It is postulated that both
      the progressive inhibition of anaerobic glycolysis by accumulating protons
      (together with a slow decrease of the net creatine kinase reaction rate) and
      gradual increase of ATP usage during exercise, and perhaps a decrease in P/O,
      contribute to the generation of the slow component of the VO2 on-kinetics in
      skeletal muscle.

PMID- 25767030
TI  - Can intradermal administration of angiotensin II influence human heat loss
      responses during whole body heat stress?
AB  - It is unclear if angiotensin II, which can increase the production of reactive
      oxygen species (oxidative stress), modulates heat loss responses of cutaneous
      blood flow and sweating. We tested the hypothesis that angiotensin II-induced
      increases in oxidative stress impair cutaneous perfusion and sweating during rest
      and exercise in the heat. Eleven young (24 +/- 4 yr) healthy adults performed two
      30-min cycling bouts at a fixed rate of metabolic heat production (400 W) in the
      heat (35 degrees C). The first and second exercises were followed by a 20- and 40
      min recovery. Four microdialysis fibers were placed in the forearm skin for
      continuous administration of either: 1) lactated Ringer (control), 2) 10 MUM
      angiotensin II, 3) 10 mM ascorbate (an antioxidant), or 4) a combination of 10
      MUM angiotensin II + 10 mM ascorbate. Cutaneous vascular conductance (CVC; laser
      Doppler perfusion units/mean arterial pressure) and sweating (ventilated capsule)
      were evaluated at each skin site. Compared with control, angiotensin II reduced
      both CVC and sweating at baseline resting and during each recovery in the heat
      (all P < 0.05). However, during both exercise bouts, there were no differences in
      CVC or sweating between the treatment sites (all P > 0.05). When ascorbate was
      coinfused with angiotensin II, the effect of angiotensin II on sweating was
      abolished (all P > 0.05); however, its effect on CVC at baseline resting and
      during each recovery remained intact (all P < 0.05). We show angiotensin II
      impairs cutaneous perfusion independent of oxidative stress, while it impairs
      sweating through increasing oxidative stress during exposure to an ambient heat
      stress before and following exercise.

PMID- 25767032
TI  - Torque decrease during submaximal evoked contractions of the quadriceps muscle is
      linked not only to muscle fatigue.
AB  - The aim of this study was to analyze the neuromuscular mechanisms involved in the
      torque decrease induced by submaximal electromyostimulation (EMS) of the
      quadriceps muscle. It was hypothesized that torque decrease after EMS would
      reflect the fatigability of the activated motor units (MUs), but also a reduction
      in the number of MUs recruited as a result of changes in axonal excitability
      threshold. Two experiments were performed on 20 men to analyze 1) the
      supramaximal twitch superimposed and evoked at rest during EMS (Experiment 1, n =
      9) and 2) the twitch response and torque-frequency relation of the MUs activated
      by EMS (Experiment 2, n = 11). Torque loss was assessed by 15 EMS-evoked
      contractions (50 Hz; 6 s on/6 s off), elicited at a constant intensity that
      evoked 20% of the maximal voluntary contraction (MVC) torque. The same
      stimulation intensity delivered over the muscles was used to induce the torque
      frequency relation and the single electrical pulse evoked after each EMS
      contraction (Experiment 2). In Experiment 1, supramaximal twitch was induced by
      femoral nerve stimulation. Torque decreased by ~60% during EMS-evoked
      contractions and by only ~18% during MVCs. This was accompanied by a rightward
      shift of the torque-frequency relation of MUs activated and an increase of the
      ratio between the superimposed and posttetanic maximal twitch evoked during EMS
      contraction. These findings suggest that the torque decrease observed during
      submaximal EMS-evoked contractions involved muscular mechanisms but also a
      reduction in the number of MUs recruited due to changes in axonal excitability.

PMID- 25767029
TI  - Emerging roles of GPER in diabetes and atherosclerosis.
AB  - The G protein-coupled estrogen receptor (GPER) is a 7-transmembrane receptor
      implicated in rapid estrogen signaling. Originally cloned from vascular
      endothelial cells, GPER plays a central role in the regulation of vascular tone
      and cell growth as well as lipid and glucose homeostasis. This review highlights
      our knowledge of the physiological and pathophysiological functions of GPER in
      the pancreas, peripheral and immune tissues, and the arterial vasculature. Recent
      findings on its roles in obesity, diabetes, and atherosclerosis, including GPER
      dependent regulation of lipid metabolism and inflammation, are presented. The
      therapeutic potential of targeting GPER-dependent pathways in chronic diseases
      such as coronary artery disease and diabetes and in the context of menopause is
      also discussed. 

PMID- 25767033
TI  - Mechanical ventilation triggers abnormal mitochondrial dynamics and morphology in
      the diaphragm.
AB  - The diaphragm is a unique skeletal muscle designed to be rhythmically active
      throughout life, such that its sustained inactivation by the medical intervention
      of mechanical ventilation (MV) represents an unanticipated physiological state in
      evolutionary terms. Within a short period after initiating MV, the diaphragm
      develops muscle atrophy, damage, and diminished strength, and many of these
      features appear to arise from mitochondrial dysfunction. Notably, in response to
      metabolic perturbations, mitochondria fuse, divide, and interact with neighboring
      organelles to remodel their shape and functional properties-a process
      collectively known as mitochondrial dynamics. Using a quantitative electron
      microscopy approach, here we show that diaphragm contractile inactivity induced
      by 6 h of MV in mice leads to fragmentation of intermyofibrillar (IMF) but not
      subsarcolemmal (SS) mitochondria. Furthermore, physical interactions between
      adjacent organellar membranes were less abundant in IMF mitochondria during MV.
      The profusion proteins Mfn2 and OPA1 were unchanged, whereas abundance and
      activation status of the profission protein Drp1 were increased in the diaphragm
      following MV. Overall, our results suggest that mitochondrial morphological
      abnormalities characterized by excessive fission-fragmentation represent early
      events during MV, which could potentially contribute to the rapid onset of
      mitochondrial dysfunction, maladaptive signaling, and associated contractile
      dysfunction of the diaphragm.

PMID- 25767034
TI  - [18F]-FDG positron emission tomography--an established clinical tool opening a
      new window into exercise physiology.
AB  - Positron emission tomography (PET) with [(18)F]-fluorodeoxyglucose (FDG) is an
      established clinical tool primarily used to diagnose and evaluate disease status
      in patients with cancer. PET imaging using FDG can be a highly valuable tool to
      investigate normal human physiology by providing a noninvasive, quantitative
      measure of glucose uptake into various cell types. Over the past years it has
      also been increasingly used in exercise physiology studies to identify changes in
      glucose uptake, metabolism, and muscle activity during different exercise
      modalities. Metabolically active cells transport FDG, an (18)fluorine-labeled
      glucose analog tracer, from the blood into the cells where it is then
      phosphorylated but not further metabolized. This metabolic trapping process forms
      the basis of this method's use during exercise. The tracer is given to a
      participant during an exercise task, and the actual PET imaging is performed
      immediately after the exercise. Provided the uptake period is of sufficient
      duration, and the imaging is performed shortly after the exercise; the captured
      image strongly reflects the metabolic activity of the cells used during the task.
      When combined with repeated blood sampling to determine tracer blood
      concentration over time, also known as the input function, glucose uptake rate of
      the tissues can be quantitatively calculated. This synthesis provides an
      accounting of studies using FDG-PET to measure acute exercise-induced skeletal
      muscle activity, describes the advantages and limitations of this imaging
      technique, and discusses its applications to the field of exercise physiology. 

PMID- 25767035
TI  - Muscle-specific glucose and free fatty acid uptake after sprint interval and
      moderate-intensity training in healthy middle-aged men.
AB  - We tested the hypothesis that sprint interval training (SIT) causes larger
      improvements in glucose and free fatty acid uptake (FFAU) in lower and upper body
      muscles than moderate-intensity training (MIT). Twenty-eight healthy, untrained,
      middle-aged men were randomized into SIT (n = 14, 4-6 * 30 s of all-out cycling/4
      min recovery) and MIT groups [n = 14, 40-60 min cycling at 60% of peak O2 uptake
      (Vo2 peak)] and completed six training sessions within 2 wk. Pre- and
      postmeasurements included Vo2 peak, whole body (M-value), muscle-specific insulin
      stimulated glucose uptake (GU), and fasting FFAU measured with positron emission
      tomography in thigh [quadriceps femoris (QF) and hamstrings] and upper body
      (deltoids, biceps, and triceps brachii) muscles. Vo2 peak and M-value improved
      significantly by 6 and 12% in SIT, and 3 and 8% in MIT, respectively,. GU
      increased significantly only in the QF, and there was no statistically
      significant difference between the training modes. GU increased in all four heads
      of QF in response to SIT, but only in the vasti muscles in response to MIT,
      whereas in rectus femoris the response was completely lacking. Training response
      in FFAU in QF was smaller and nonsignificant, but it also differed between the
      training modes in the rectus femoris. In conclusion, SIT and MIT increased
      insulin-stimulated GU only in the main working muscle QF and not in the upper
      body muscles. In addition, the biarticular rectus femoris did not respond to
      moderate-intensity training, reflecting most probably poor activation of it
      during moderate-intensity cycling.

PMID- 25767036
TI  - Effect of unilateral nasal obstruction on tongue protrusion forces in growing
      rats.
AB  - Mouth breathing caused by nasal obstruction affects the normal growth and
      development of craniofacial structures, including changes in the orofacial
      muscles. Tongue muscles play an important role in patency of the pharyngeal
      airway, and changes in the breathing pattern may influence tongue function. The
      purpose of this study was to evaluate the effect of unilateral nasal obstruction
      during growth on contractile properties of the tongue-protruding muscles. Sixty 6
      day-old male Wistar albino rats were divided randomly into control (n = 30) and
      experimental (n = 30) groups. Rats in the experimental group underwent a
      unilateral nasal obstruction after cauterization of the external nostril at the
      age of 8 days, and muscle contractile characteristics were measured at 5, 7, and
      9 wk of age. The specific parameters measured were twitch force, contraction
      time, half-decay time, tetanic force, and fatigue index. Repeated-measures
      multivariate analysis of variance was used for intergroup and intragroup
      statistical comparisons. Twitch contraction force and half-decay time were
      significantly increased in the experimental group at all ages. Tetanic forces at
      60 and 80 Hz were significantly higher in the experimental group at all ages. The
      fatigue index was decreased significantly in the experimental group at the age of
      5 wk. These results suggest that early unilateral nasal obstruction may increase
      the contraction force of the tongue-protruding muscles and prolong the duration
      of muscle contraction, which may influence the shape and development of the
      craniofacial complex.

PMID- 25767037
TI  - Cationic amphipathic peptides KT2 and RT2 are taken up into bacterial cells and
      kill planktonic and biofilm bacteria.
AB  - We investigated the mechanisms of two tryptophan-rich antibacterial peptides (KT2
      and RT2) obtained in a previous optimization screen for increased killing of both
      Gram-negative and Gram-positive bacteria pathogens. At their minimal inhibitory
      concentrations (MICs), these peptides completely killed cells of multidrug
      resistant, enterohemorrhagic pathogen Escherichia coli O157:H7 within 1-5 min. In
      addition, both peptides exhibited anti-biofilm activity at sub-MIC levels.
      Indeed, these peptides prevented biofilm formation and triggered killing of cells
      in mature E. coli O157:H7 biofilms at 1 MUM. Both peptides bound to bacterial
      surface LPS as assessed using the dansyl-polymyxin displacement assay, and were
      able to interact with the lipids of liposomes as determined by observing a
      tryptophan blue shift. Interestingly, even though these peptides were highly
      antimicrobial, they did not induce pore formation or aggregates in bacterial cell
      membranes. Instead these peptides readily penetrated into bacterial cells as
      determined by confocal microscopy of labeled peptides. DNA binding assays
      indicated that both peptides bound to DNA with higher affinity than the positive
      control peptide buforin II. We propose that cationic peptides KT2 and RT2 bind to
      negatively-charged LPS to enable self-promoted uptake and, subsequently interact
      with cytoplasmic membrane phospholipids through their hydrophobic domains
      enabling translocation across the bacterial membrane and entry into cells within
      minutes and binding to DNA and other cytoplasmic membrane. Due to their dual
      antimicrobial and anti-biofilm activities, these peptides may find use as an
      alternative to (or in conjunction with) conventional antibiotics to treat acute
      infections caused by planktonic bacteria and chronic, biofilm-related infections.

PMID- 25767038
TI  - Docosahexaenoic acid promotes micron scale liquid-ordered domains. A comparison
      study of docosahexaenoic versus oleic acid containing phosphatidylcholine in raft
      like mixtures.
AB  - The understanding of the functional role of the lipid diversity in biological
      membranes is a major challenge. Lipid models have been developed to address this
      issue by using lipid mixtures generating liquid-ordered (Lo)/liquid-disordered
      (Ld) immiscibility. The present study examined mixtures comprising Egg
      sphingomyelin (SM), cholesterol (chol) and phosphatidylcholine (PC) either
      containing docosahexaenoic (PDPC) or oleic acid (POPC). The mixtures were
      examined in terms of their capability to induce phase separation at the micron-
      and nano-scales. Fluorescence microscopy, electron spin resonance (ESR), X-ray
      diffraction (XRD) and calorimetry methods were used to analyze the lateral
      organization of the mixtures. Fluorescence microscopy of giant vesicles could
      show that the temperature of the micron-scale Lo/Ld miscibility is higher for
      PDPC than for POPC ternary mixtures. At 37 degrees C, no micron-scale Lo/Ld phase
      separation could be identified in the POPC containing mixtures while it was
      evident for PDPC. In contrast, a phase separation was distinguished for both PC
      mixtures by ESR and XRD, indicative that PDPC and POPC mixtures differed in
      micron vs nano domain organization. Compared to POPC, the higher line tension of
      the Lo domains observed in PDPC mixtures is assumed to result from the higher
      difference in Lo/Ld order parameter rather than hydrophobic mismatch. 

PMID- 25767040
TI  - Multiplexity versus correlation: the role of local constraints in real
      multiplexes.
AB  - Several systems can be represented as multiplex networks, i.e. in terms of a
      superposition of various graphs, each related to a different mode of connection
      between nodes. Hence, the definition of proper mathematical quantities aiming at
      capturing the added level of complexity of those systems is required. Various
      steps in this direction have been made. In the simplest case, dependencies
      between layers are measured via correlation-based metrics, a procedure that we
      show to be equivalent to the use of completely homogeneous benchmarks specifying
      only global constraints. However, this approach does not take into account the
      heterogeneity in the degree and strength distributions, which is instead a
      fundamental feature of real-world multiplexes. In this work, we compare the
      observed dependencies between layers with the expected values obtained from
      maximum-entropy reference models that appropriately control for the observed
      heterogeneity in the degree and strength distributions. This information
      theoretic approach results in the introduction of novel and improved multiplexity
      measures that we test on different datasets, i.e. the International Trade Network
      and the European Airport Network. Our findings confirm that the use of
      homogeneous benchmarks can lead to misleading results, and highlight the
      important role played by the distribution of hubs across layers. 

PMID- 25767039
TI  - Phase I trial of systemic intravenous infusion of interleukin-13-Pseudomonas
      exotoxin in patients with metastatic adrenocortical carcinoma.
AB  - Adrenocortical carcinoma (ACC) is a rare but lethal malignancy without effective
      current therapy for metastatic disease. IL-13-PE is a recombinant cytotoxin
      consisting of human interleukin-13 (IL-13) and a truncated form of Pseudomonas
      exotoxin A (PE). The main objectives of this Phase I dose-escalation trial were
      to assess the maximum-tolerated dose (MTD), safety, and pharmacokinetics (PK) of
      IL-13-PE in patients with metastatic ACC. Eligible patients had confirmed IL-13
      receptor alpha 2 (IL-13Ralpha2) expressions in their tumors. IL-13-PE at dose of
      1-2 MUg/kg was administered intravenously (IV) on day 1, 3, and 5 in a 4-week
      cycle. Six patients received 1 MUg/kg and two patients received 2 MUg/kg of IL-13
      PE. Dose-limiting toxicity was observed at 2 MUg/kg, at which patients exhibited
      thrombocytopenia and renal insufficiency without requiring dialysis. PK analysis
      demonstrated that at MTD, the mean maximum serum concentration (Cmax ) of IL-13
      PE was 21.0 ng/mL, and the terminal half-life of IL-13-PE was 30-39 min. Two
      (25%) of the eight patients had baseline neutralizing antibodies against PE.
      Three (75%) of the remaining four tested patients developed neutralizing
      antibodies against IL-13-PE within 14-28 days of initial treatment. Of the five
      patients treated at MTD and assessed for response, one patient had stable disease
      for 5.5 months before disease progression; the others progressed within 1-2
      months. In conclusion, systemic IV administration of IL-13-PE is safe at 1
      MUg/kg. All tested patients developed high levels of neutralizing antibodies
      during IL-13-PE treatment. Use of strategies for immunodepletion before IL-13-PE
      treatment should be considered in future trials. 

PMID- 25767041
TI  - Novel carbapenem chalcone derivatives: synthesis, cytotoxicity and molecular
      docking studies.
AB  - A one-pot efficient synthetic protocol is described for the synthesis of
      carbapenem chalcone derivatives using AAPTMS@MCM-41 heterogeneous catalyst.
      Various substituted aromatic aldehydes were attached to highly chiral and
      reactive carbapenem using this approach. The cytotoxic activity evaluation of all
      synthesized compounds was performed against lung cancer cell lines (A-549) and
      breast cancer cell lines (MCF-7) using the MTT assay. Among the tested compounds,
      compound CPC-2 showed better activity against MCF-7 cell lines with an IC50 value
      2.52 MUM mL(-1); whereas compound CPC-4 showed good activity against A-549 cell
      lines with an IC50 value 1.59 MUM mL(-1). In order to support the observed
      activity profiles, the representative compounds were flexibly docked into the
      active sites of the Anaplastic Lymphoma Kinase (ALK) enzyme and the Estrogen
      receptor (ERbeta). The most active anticancer compounds exhibited stronger
      binding affinities for proteins. 

PMID- 25767042
TI  - [Psychiatric disorders in palliative care and at the end of life].
AB  - Patients confronted to advanced organic diseases at a palliative stage can
      present psychological distress that might announce the occurrence of genuine
      psychiatric disorders. Some frequent and comprehensible symptoms such as sadness,
      mild agitation, anxiety or more disturbing such as hallucinations, delusions or
      suicidal ideations must alert the clinician who should not minimize them by
      attributing them in a reactive way to the consequences of the evolution of
      physical disease or treatment's side effects. Literature data regarding
      psychiatric disorders (mainly anxiety disorders, delirium and depressive
      disorders) in palliative care are emerging and can guide clinicians in their role
      to detect them and providing early and efficient management. Occurrence of
      warning symptoms of psychiatric disorders can impaired quality of life and impact
      the prognosis of patients already weakened by the context of an advanced physical
      disease. The clinician will have to be careful to any psychiatric prodromic
      symptom and not hesitate to treat and to refer if necessary to a heath mental
      professional.

PMID- 25767043
TI  - Fibromuscular dysplasia and coronary heart disease.

PMID- 25767044
TI  - Coherent quantum depletion of an interacting atom condensate.
AB  - Sufficiently strong interactions promote coherent quantum transitions in spite of
      thermalization and losses, which are the adversaries of delicate effects such as
      reversibility and correlations. In atomic Bose-Einstein condensates (BECs),
      strong atom-atom interactions can eject atoms from the BEC to the normal
      component, yielding quantum depletion instead of temperature depletion. A recent
      experiment has already been verified to overcome losses. Here I show that it also
      achieves coherent quantum-depletion dynamics in a BEC swept fast enough from weak
      to strong atom-atom interactions. The elementary coherent process first excites
      the normal component into a liquid state that evolves into a spherical shell
      state, where the atom occupation peaks at a finite momentum to shield 50% of the
      BEC atoms from annihilation. The identified coherent processes resemble ultrafast
      semiconductor excitations expanding the scope of BEC explorations to many-body
      non-equilibrium studies. 

PMID- 25767045
TI  - Theory of solar energy materials.

PMID- 25767046
TI  - Dendritic spine dysgenesis: An emerging concept in neuropsychiatric disease.

PMID- 25767047
TI  - Pyogenic arthritis of native joints in non-intravenous drug users: A detailed
      analysis of 268 cases attended in a tertiary hospital over a 22-year period.
AB  - OBJECTIVE: To analyze the clinical features, microbiological spectrum, diagnostic
      procedures and outcomes in native joint pyogenic arthritis among non-intravenous
      drug users. METHODS: We collected all microbiologically proved cases of
      infectious arthritis at our hospital between 1992 and 2013. Patients with
      prosthetic joint infection were excluded, as were patients with non-pyogenic
      arthritis and intravenous drug users. RESULTS: We identified 268 patients; the
      mean age was 61 +/- 14.7 years and 62% were men. The incidence increased over the
      period of study. In 188 patients (70%), one or more underlying medical illnesses
      were found. The mean symptom duration was 8.9 +/- 9.5 days. Globally, 311
      affected joints were found, 232 (75%) involving peripheral joints and 79 (25%)
      axial joints. Staphylococci (55%) and Streptococci (29%) were the predominant
      microorganisms. Blood cultures were positive in 78% (173/223) of the cases. In 81
      patients (30%), one or more concomitant infectious processes were found.
      Antimicrobial therapy was prescribed 4-8 weeks in most cases, and surgical
      drainage was performed in 65% of patients. Four patients relapsed and 23 (8%)
      died. CONCLUSIONS: The prevalence of pyogenic native joint arthritis in non
      intravenous drug users is increasing, frequently affecting old patients with
      underlying medical conditions. Although large joints are the most frequently
      compromised, the involvement of axial joints is a relevant feature that has not
      been recognized in other series. Staphylococci and Streptococci are the main
      causative agents. Bacteremia and concomitant infectious processes are frequent
      complications. Diagnostic delay and mortality continue to be important concerns.

PMID- 25767048
TI  - Prevalence of BRAF and NRAS mutations in cutaneous melanoma patients in Taiwan.
AB  - BACKGROUND/PURPOSE: BRAF and NRAS mutations have been described in melanomas
      among Caucasians and some Asian populations. However, few large-scale studies
      have investigated the status and clinical significance of BRAF and NRAS mutations
      in a Taiwanese population. METHODS: Melanoma samples (n = 119) were analyzed for
      mutations in exons 11 and 15 of the BRAF gene, and in exons 1 and 2 of the NRAS
      gene. The samples were studied in genomic DNA, using polymerase chain reaction
      amplification and Sanger sequencing. Mutations of the BRAF and NRAS genes were
      then correlated with clinicopathological features and patients' prognosis.
      RESULTS: The incidence of somatic mutations within the BRAF and NRAS genes was
      14.3% (17/119 patients) and 10.1% (12/119 patients), respectively. Among the 17
      patients with BRAF mutations, 15 (88.2%) had V600E mutations. BRAF mutation was
      frequently detected in younger patients (p = 0.0035), in thin melanomas (p =
      0.0181), and in melanomas with less ulceration (p = 0.0089). NRAS mutation was
      more often seen in patients with lymph node metastasis (p = 0.0332). Both BRAF
      and NRAS mutations were not significantly correlated with overall survival and
      disease-free survival. CONCLUSION: As BRAF and NRAS mutations are rare in Taiwan,
      BRAF- or NRAS-targeted therapies may be effective only for selected Taiwanese
      melanoma patients.

PMID- 25767050
TI  - Novel pseudo[2]rotaxanes constructed by the self-assembly of dibenzyl
      tetramethylene bis-carbamate derivatives and per-ethylated pillar[5]arene.
AB  - Novel neutral guest molecules, G1-G7, are studied for their host-guest
      complexation with per-ethylated pillar[5]arene (EtP[5]A). Among them, G1 and G7 ,
      dibenzyl tetramethylene bis-carbamate derivatives, are found to afford a novel
      stable pseudo[2]rotaxane with EtP[5]A, respectively, and G7 ? EtP[5]A shows
      photoresponsive properties.

PMID- 25767049
TI  - Correcting positional correlations in Affymetrix(r) genome chips.
AB  - We report and model a previously undescribed systematic error causing spurious
      excess correlations that depend on the distance between probes on Affymetrix(r)
      microarrays. The phenomenon affects pairs of features with large chip
      separations, up to over 100 probes apart. The effect may have a significant
      impact on analysis of correlations in large collections of expression data, where
      the systematic experimental errors are repeated in many data sets. Examples of
      such studies include analysis of functions and interactions in groups of genes,
      as well as global properties of genomes. We find that the average correlations
      between probes on Affymetrix microarrays are larger for smaller chip distances,
      which points out to a previously undescribed positional artifact. The magnitude
      of the artifact depends on the design of the chip, and we find it to be
      especially high for the yeast S98 microarray, where spurious excess correlations
      reach 0.1 at a distance of 50 probes. We have designed an algorithm to correct
      this bias and provide new data sets with the corrected expression values. This
      algorithm was successfully implemented to remove the positional artifact from the
      S98 chip data while preserving the integrity of the data. 

PMID- 25767051
TI  - Changing fitness of a necrotrophic plant pathogen under increasing temperature.
AB  - Warmer temperatures associated with climate change are expected to have a direct
      impact on plant pathogens, challenging crops and altering plant disease profiles
      in the future. In this study, we have investigated the effect of increasing
      temperature on the pathogenic fitness of Fusarium pseudograminearum, an important
      necrotrophic plant pathogen associated with crown rot disease of wheat in
      Australia. Eleven wheat lines with different levels of crown rot resistance were
      artificially inoculated with F. pseudograminearum and maintained at four diurnal
      temperatures 15/15 degrees C, 20/15 degrees C, 25/15 degrees C and 28/15 degrees
      C in a controlled glasshouse. To quantify the success of F. pseudograminearum
      three fitness measures, these being disease severity, pathogen biomass in stem
      base and flag leaf node, and deoxynivalenol (DON) in stem base and flag leaf node
      of mature plants were used. F. pseudograminearum showed superior overall fitness
      at 15/15 degrees C, and this was reduced with increasing temperature. Pathogen
      fitness was significantly influenced by the level of crown rot resistance of
      wheat lines, but the influence of line declined with increasing temperature.
      Lines that exhibited superior crown rot resistance in the field were generally
      associated with reduced overall pathogen fitness. However, the relative
      performance of the wheat lines was dependent on the measure of pathogen fitness,
      and lines that were associated with one reduced measure of pathogen fitness did
      not always reduce another. There was a strong correlation between DON in stem
      base tissue and disease severity, but length of browning was not a good predictor
      of Fusarium biomass in the stem base. We report that a combination of host
      resistance and rising temperature will reduce pathogen fitness under increasing
      temperature, but further studies combining the effect of rising CO2 are essential
      for more realistic assessments. 

PMID- 25767052
TI  - Concurrence of rule- and similarity-based mechanisms in artificial grammar
      learning.
AB  - A current theoretical debate regards whether rule-based or similarity-based
      learning prevails during artificial grammar learning (AGL). Although the majority
      of findings are consistent with a similarity-based account of AGL it has been
      argued that these results were obtained only after limited exposure to study
      exemplars, and performance on subsequent grammaticality judgment tests has often
      been barely above chance level. In three experiments the conditions were
      investigated under which rule- and similarity-based learning could be applied.
      Participants were exposed to exemplars of an artificial grammar under different
      (implicit and explicit) learning instructions. The analysis of receiver operating
      characteristics (ROC) during a final grammaticality judgment test revealed that
      explicit but not implicit learning led to rule knowledge. It also demonstrated
      that this knowledge base is built up gradually while similarity knowledge
      governed the initial state of learning. Together these results indicate that rule
      and similarity-based mechanisms concur during AGL. Moreover, it could be
      speculated that two different rule processes might operate in parallel; bottom-up
      learning via gradual rule extraction and top-down learning via rule testing.
      Crucially, the latter is facilitated by performance feedback that encourages
      explicit hypothesis testing. 

PMID- 25767053
TI  - A molecular dynamics study of model SI clathrate hydrates: the effect of guest
      size and guest-water interaction on decomposition kinetics.
AB  - One of the options suggested for methane recovery from natural gas hydrates is
      molecular replacement of methane by suitable guests like CO2 and N2. This
      approach has been found to be feasible through many experimental and molecular
      dynamics simulation studies. However, the long term stability of the resultant
      hydrate needs to be evaluated; the decomposition rate of these hydrates is
      expected to depend on the interaction between these guest and water molecules. In
      this work, molecular dynamics simulation has been performed to illustrate the
      effect of guest molecules with different sizes and interaction strengths with
      water on structure I (SI) hydrate decomposition and hence the stability. The van
      der Waals interaction between water of hydrate cages and guest molecules is
      defined by Lennard Jones potential parameters. A wide range of parameter spaces
      has been scanned by changing the guest molecules in the SI hydrate, which acts as
      a model gas for occupying the small and large cages of the SI hydrate. All
      atomistic simulation results show that the stability of the hydrate is sensitive
      to the size and interaction of the guest molecules with hydrate water. The
      increase in the interaction of guest molecules with water stabilizes the hydrate,
      which in turn shows a slower rate of hydrate decomposition. Similarly guest
      molecules with a reasonably small (similar to Helium) or large size increase the
      decomposition rate. The results were also analyzed by calculating the structural
      order parameter to understand the dynamics of crystal structure and correlated
      with the release rate of guest molecules from the solid hydrate phase. The
      results have been explained based on the calculation of potential energies felt
      by guest molecules in amorphous water, hydrate bulk and hydrate-water interface
      regions. 

PMID- 25767054
TI  - Interaction of Globular Plasma Proteins with Water-Soluble CdSe Quantum Dots.
AB  - The interactions between water-soluble semiconductor quantum dots [hydrophilic 3
      mercaptopropionic acid (MPA)-coated CdSe] and three globular plasma proteins,
      namely, bovine serum albumin (BSA), beta-lactoglobulin (beta-Lg) and human serum
      albumin (HSA), are investigated. Acidic residues of protein molecules form
      electrostatic interactions with these quantum dots (QDs). To determine the
      stoichiometry of proteins bound to QDs, we used dynamic light scattering (DLS)
      and zeta potential techniques. Fluorescence resonance energy transfer (FRET)
      experiments revealed energy transfer from tryptophan residues in the proteins to
      the QD particles. Quenching of the intrinsic fluorescence of protein molecules
      was noticed during this binding process (hierarchy HSA<beta-Lg <BSA, lower
      binding affinity for hydrophobic protein molecules). Upon binding with QD
      particles, the protein molecules underwent substantial conformational changes at
      the secondary-structure level (50 % helicity lost), due to loss in hydration.

PMID- 25767055
TI  - Dienogest reduces HSD17beta1 expression and activity in endometriosis.
AB  - Endometriosis is an estrogen-dependent disease. Abnormally biosynthesized
      estrogens in endometriotic tissues induce the growth of the lesion and worsen
      endometriosis-associated pelvic pain. Dienogest (DNG), a selective progesterone
      receptor agonist, is widely used to treat endometriosis and efficiently relieves
      the symptoms. However, its pharmacological action remains unknown. In this study,
      we elucidated the effect of DNG on enzymes involved in local estrogen metabolism
      in endometriosis. Surgically obtained specimens of 23 ovarian endometriomas (OE)
      and their homologous endometrium (EE), ten OE treated with DNG (OE w/D), and 19
      normal endometria without endometriosis (NE) were analyzed. Spheroid cultures of
      stromal cells (SCs) were treated with DNG and progesterone. The expression of
      aromatase, 17beta-hydroxysteroid dehydrogenase 1 (HSD17beta1), HSD17beta2,
      HSD17beta7, HSD17beta12, steroid sulfatase (STS), and estrogen sulfotransferase
      (EST) was evaluated by real-time quantitative PCR. The activity and protein level
      of HSD17beta1 were measured with an enzyme assay using radiolabeled estrogens and
      immunohistochemistry respectively. OESCs showed increased expression of
      aromatase, HSD17beta1, STS, and EST, along with decreased HSD17beta2 expression,
      when compared with stromal cells from normal endometria without endometriosis
      (NESCs) (P<0.01) or stromal cells from homologous endometrium (EESCs) (P<0.01).
      In OESCs, DNG inhibited HSD17beta1 expression and enzyme activity at 10(-7) M
      (P<0.01). Results of immunohistochemical analysis displayed reduced HSD17beta1
      staining intensity in OE w/D (P<0.05). In conclusion, DNG exerts comprehensive
      inhibition of abnormal estrogen production through inhibition of aromatase and
      HSD17beta1, contributing to a therapeutic effect of DNG on endometriosis.

PMID- 25767056
TI  - Chronic erythropoietin treatment improves diet-induced glucose intolerance in
      rats.
AB  - Erythropoietin (EPO) ameliorates glucose metabolism through mechanisms not fully
      understood. In this study, we investigated the effect of EPO on glucose
      metabolism and insulin signaling in skeletal muscle. A 2-week EPO treatment of
      rats fed with a high-fat diet (HFD) improved fasting glucose levels and glucose
      tolerance, without altering total body weight or retroperitoneal fat mass.
      Concomitantly, EPO partially rescued insulin-stimulated AKT activation, reduced
      markers of oxidative stress, and restored heat-shock protein 72 expression in
      soleus muscles from HFD-fed rats. Incubation of skeletal muscle cell cultures
      with EPO failed to induce AKT phosphorylation and had no effect on glucose uptake
      or glycogen synthesis. We found that the EPO receptor gene was expressed in
      myotubes, but was undetectable in soleus. Together, our results indicate that EPO
      treatment improves glucose tolerance but does not directly activate the
      phosphorylation of AKT in muscle cells. We propose that the reduced systemic
      inflammation or oxidative stress that we observed after treatment with EPO could
      contribute to the improvement of whole-body glucose metabolism.

PMID- 25767058
TI  - Postsynthetic ligand exchange for the synthesis of benzotriazole-containing
      zeolitic imidazolate framework.
AB  - The introduction of a triazole-based ligand to the zeolitic imidazolate framework
      7 via a postsynthetic ligand exchange strategy not only maintains its framework,
      high stability and morphology, but also provides extra uncoordinated nitrogen
      atoms to improve the pi-pi and Lewis acid-base interactions. 

PMID- 25767057
TI  - Cell wall maturation of Arabidopsis trichomes is dependent on exocyst subunit
      EXO70H4 and involves callose deposition.
AB  - Arabidopsis (Arabidopsis thaliana) leaf trichomes are single-cell structures with
      a well-studied development, but little is understood about their function.
      Developmental studies focused mainly on the early shaping stages, and little
      attention has been paid to the maturation stage. We focused on the EXO70H4
      exocyst subunit, one of the most up-regulated genes in the mature trichome. We
      uncovered EXO70H4-dependent development of the secondary cell wall layer, highly
      autofluorescent and callose rich, deposited only in the upper part of the
      trichome. The boundary is formed between the apical and the basal parts of mature
      trichome by a callose ring that is also deposited in an EXO70H4-dependent manner.
      We call this structure the Ortmannian ring (OR). Both the secondary cell wall
      layer and the OR are absent in the exo70H4 mutants. Ecophysiological aspects of
      the trichome cell wall thickening include interference with antiherbivore defense
      and heavy metal accumulation. Ultraviolet B light induces EXO70H4 transcription
      in a CONSTITUTIVE PHOTOMORPHOGENIC1-dependent way, resulting in stimulation of
      trichome cell wall thickening and the OR biogenesis. EXO70H4-dependent trichome
      cell wall hardening is a unique phenomenon, which may be conserved among a
      variety of the land plants. Our analyses support a concept that Arabidopsis
      trichome is an excellent model to study molecular mechanisms of secondary cell
      wall deposition.

PMID- 25767059
TI  - Traditional karyotyping vs copy number variation sequencing for detection of
      chromosomal abnormalities associated with spontaneous miscarriage.
AB  - OBJECTIVES: To compare the performance of traditional G-banding karyotyping with
      that of copy number variation sequencing (CNV-Seq) for detection of chromosomal
      abnormalities associated with miscarriage. METHODS: Products of conception (POC)
      were collected from spontaneous miscarriages. Chromosomal abnormalities were
      detected using high-resolution G-banding karyotyping and CNV sequencing.
      Quantitative fluorescent polymerase chain reaction analysis of maternal and POC
      DNA for short tandem repeat (STR) markers was used to both monitor maternal cell
      contamination and confirm the chromosomal status and sex of the miscarriage
      tissue. RESULTS: A total of 64 samples of POC, comprising 16 with an abnormal and
      48 with a normal karyotype, were selected and coded for analysis by CNV-Seq. CNV
      Seq results were concordant for 14 (87.5%) of the 16 gross chromosomal
      abnormalities identified by karyotyping, including 11 autosomal trisomies and
      three sex chromosomal aneuploidies (45,X). Of the two discordant results, a
      69,XXX polyploidy was missed by CNV-Seq, although supporting STR marker analysis
      confirmed the triploidy. In contrast, CNV-Seq identified a sample with 45,X
      karyotype as a 45,X/46,XY mosaic. In the remaining 48 samples of POC with a
      normal karyotype, CNV-Seq detected a 2.58-Mb 22q deletion associated with
      DiGeorge syndrome and nine different smaller CNVs of no apparent clinical
      significance. CONCLUSIONS: CNV-Seq used in parallel with STR profiling is a
      reliable and accurate alternative to karyotyping for identifying chromosome copy
      number abnormalities associated with spontaneous miscarriage.

PMID- 25767060
TI  - A Diagnosis of Insomnia Is Associated With Differential Expression of Sleep
      Regulating Genes in Military Personnel.
AB  - Sleep disturbance is a common and disturbing symptom in military personnel, with
      many individuals progressing to the development of insomnia, which is
      characterized by increased arousals, wakefulness after sleep onset, and distorted
      sleep architecture. The molecular mechanisms underlying insomnia remain elusive,
      limiting future therapeutic development to address this critical issue. We
      examined whole gene expression profiles associated with insomnia. We compared
      subjects with insomnia (n = 25) to controls (n = 13) without insomnia using
      microarray gene expression profiles obtained from peripheral samples of whole
      blood obtained from military personnel. Compared to controls, participants with
      insomnia had differential expression of 44 transcripts from 43 identified genes.
      Among the identified genes, urotensin 2 was downregulated by more than 6 times in
      insomnia participants, and the fold-change remained significant after controlling
      for depression, posttraumatic stress disorder, and medication use. Urotensin 2 is
      involved in regulation of orexin A and B activity and rapid eye movement during
      sleep. These findings suggest that differential expression of these sleep
      regulating genes contributes to symptoms of insomnia and, specifically, that
      switching between rapid eye movement and nonrapid eye movement sleep stages
      underlies insomnia symptoms. Future work to identify therapeutic agents that are
      able to regulate these pathways may provide novel treatments for insomnia.

PMID- 25767061
TI  - Most clinical trials fail to meet FDA requirement to publish results within a
      year.

PMID- 25767062
TI  - Effective use of Biobrane as a temporary wound dressing prior to definitive split
      skin graft in the treatment of severe burn: A retrospective analysis.
AB  - AIMS: To report on the use of Biobrane, a synthetic skin substitute, as a
      temporary wound cover in patients with severe burn. In particular we wished to
      examine the role of Biobrane in maintaining a healthy wound bed following
      surgical excision and identify factors associated with regrafting. METHODS: A
      retrospective case series review was performed on patients with severe burns (>=
      20% TBSA), admitted to the Victorian Adult Burns Service, in Melbourne, from
      January 2009 to June 2012. Logistic regression analysis was performed to identify
      factors associated with regrafting. RESULTS: Out of 58 patients with median %TBSA
      burn of 30%, 22 patients (37.9%) required regrafting of at least one area
      previously treated with Biobrane and split-skin graft. On univariate analysis,
      need for regrafting was significantly associated with increasing %TBSA (OR 1.04,
      95% CI: 1.01-1.08; p=0.02); and after multivariate analysis to adjust for this
      effect, hospital LOS (OR 1.04, 95% CI: 1.02-1.07; p=0.001); total operative time
      (OR 1.16, 95% CI; 1.06-1.28; p=0.002) and total number of surgeries (OR 1.69, 95%
      CI: 1.27-2.26, p<0.001) remained significantly associated with regrafting. Age,
      gender, time to surgical debridement and Biobrane application, and anatomical
      region were not found to be associated with regraft. CONCLUSION: At our
      institution, Biobrane has emerged as an alternative option to maintain a healthy
      wound bed after burn excision and prior to grafting. Our small number of
      extensive graft failures, small areas of regrafting and low infection rate
      following Biobrane application reflects our current experience with Biobrane.
      Precise indications and most appropriate methods for Biobrane use are yet to be
      established.

PMID- 25767063
TI  - Measurement of change in the mechanical properties of burned skin to therapist
      intervention with a vacuum device.
AB  - INTRODUCTION: The currently available clinical scales used to describe healed
      burn wounds have limitations. Quantitative measurement of the outcomes from burn
      therapy treatment would be useful in planning clinical care, resource allocation
      and research. The purpose of this study was to observe the measurements of a
      portable materials testing device before and after burn therapist intervention
      for closed burns. METHODS: A recording was taken using a hand-held vacuum device
      to measure deformation of the skin in the same location prior to and following a
      treatment session with a burn therapist in an outpatient clinic at a tertiary
      burn center. RESULTS: Twenty-eight subjects were recruited to the study.
      Statistically significant differences were noted in modulus and elasticity change
      between sheet and meshed split thickness autografts (p=0.0233). Positive change
      in modulus was correlated with increasing therapy time (R=0.46), specifically for
      meshed grafts (R=0.70). Positive change in modulus was noted in therapy time
      greater than 48 min. CONCLUSIONS: Quantitative measurement of the outcomes of
      burn therapies on the mechanical properties of healed burns is possible in an
      outpatient clinic setting. Improvement in the stiffness of burn scars was
      observed in treatment sessions that last at least 48 min.

PMID- 25767065
TI  - Do wild carnivores forage for prey or for nutrients? Evidence for nutrient
      specific foraging in vertebrate predators.
AB  - A widespread perception is that carnivores are limited by the amount of prey that
      can be captured rather than their nutritional quality, and thus have no need to
      regulate macronutrient balance. Contrary to this view, recent laboratory studies
      show macronutrient-specific food selection by both invertebrate and vertebrate
      predators, and in some cases also associated performance benefits. The question
      thus arises of whether wild predators might likewise feed selectively according
      to the macronutrient content of prey. Here we review laboratory studies
      demonstrating the regulation of macronutrient intake by invertebrate and
      vertebrate predators, and address the question of whether this is likely to also
      occur in the wild. We conclude that it is highly likely that wild predators
      select prey or selectively feed on body parts according to their macronutrient
      composition, a possibility that could have significant implications for
      ecological and foraging theory, as well as applied wildlife conservation and
      management. 

PMID- 25767064
TI  - Shot-noise limited Faraday rotation spectroscopy for detection of nitric oxide
      isotopes in breath, urine, and blood.
AB  - Measurement of NO and/or its metabolites in the various body compartments has
      transformed our understanding of biology. The inability of the current NO
      measurement methods to account for naturally occurring and experimental NO
      isotopes, however, has prevented the scientific community from fully understating
      NO metabolism in vivo. Here we present a mid-IR Faraday rotation spectrometer
      (FRS) for detection of NO isotopes. The instrument utilizes a novel dual
      modulation/demodulation (DM) FRS method which exhibits noise performance at only
      2 times the fundamental quantum shot-noise level and provides the record
      sensitivity in its class. This is achieved with a system that is fully
      autonomous, robust, transportable, and does not require cryogenic cooling. The DM
      FRS enables continuous monitoring of nitric oxide isotopes with the detection
      limits of 3.72 ppbv/Hz(1/2) to(14)NO and 0.53 ppbv/Hz(1/2) to(15)NO using only 45
      cm active optical path. This DM-FRS measurement method can be used to improve the
      performance of conventional FRS sensors targeting other radical species. The
      feasibility of the instrument to perform measurements relevant to studies of NO
      metabolism in humans is demonstrated. 

PMID- 25767066
TI  - Can clinical factors predict postoperative temporomandibular disorders in
      orthognathic patients? A retrospective study of 219 patients.
AB  - OBJECTIVE: To determine the predictive value of preoperative clinical factors for
      postoperative temporomandibular disorders (TMDs) in patients receiving combined
      surgical-orthodontic treatment. STUDY DESIGN: TMDs were classified according to
      Research Diagnostic Criteria for TMD in 219 patients. The severity of the TMD was
      scored according to the Helkimo anamnestic index (Ai) and clinical dysfunction
      index (Di). RESULTS: Anamnestic TMJ clicking was the only significant predictor
      of TMD (odds ratio [OR] = 3.61, P = .006). The mean difference between clinical
      dysfunction index points was significant for pain on masticatory muscle
      palpation. CONCLUSION: This study demonstrated that in orthognathic patients, the
      following factors had high predictive value: (1) anamnestic TMJ clicking for TMD,
      (2) TMJ clicking, TMJ pain on palpation and bimaxillary surgery for Ai worsening,
      (3) maxillary retrusion and mandibular excess for Ai improvement, and (4) pain on
      masticatory muscle palpation for Di worsening.

PMID- 25767067
TI  - Complications related to surgically assisted rapid palatal expansion.
AB  - OBJECTIVE: The goals of this retrospective clinical study were to identify
      surgically assisted rapid palatal expansion (SARPE) complications and assess
      their incidence, with the aim of informing surgeons and orthodontists of the
      risks of this widely used procedure before they recommend it to patients. STUDY
      DESIGN: Between June 2008 and July 2010, 60 patients (23 women and 37 men)
      underwent SARPE according to a defined multidisciplinary protocol at the
      University of Marmara, Istanbul, Turkey. RESULTS: Twelve patients (20%) suffered
      from nasal bleeding. Of these 12, 2 patients suffered late-onset bleeding
      beginning on postoperative day 8, and in the other 10, nasal bleeding was
      insignificant. Three patients reported excessive lacrimation postoperatively.
      Minor problems related to pain and numbness were all temporary. CONCLUSIONS:
      SARPE procedures have traditionally been reported to be associated with low
      morbidity, especially in comparison with other orthognathic surgical procedures.
      However, many complications have been reported.

PMID- 25767068
TI  - Should aspirin be stopped before tooth extraction? A meta-analysis.
AB  - OBJECTIVE: To carry out a standard meta-analysis to determine if aspirin should
      be stopped before tooth extraction. STUDY DESIGN: The PubMed, ScienceDirect,
      EBSCOhost, and Science Citation Index databases were searched for studies
      published up to September 30, 2014. Eligible studies were restricted to
      randomized controlled trials (RCTs) and controlled, nonrandomized trials.
      RESULTS: Three RCTs and seven controlled trials met the inclusion criteria
      (covering 1752 patients: 529 on aspirin therapy and 1223 not on aspirin therapy).
      The results showed that the risk of postoperative hemorrhage was significantly
      higher in patients on aspirin therapy (relative risk [RR] = 2.46; 95% confidence
      interval [CI]: 1.45-4.81) but that bleeding time (BT) was not significantly
      different between the two groups (standardized mean difference [SMD] = 0.63; 95%
      CI: -0.04 to 1.31). Sensitivity analyses showed that the results were unstable.
      CONCLUSIONS: We could reach a conclusion that BT is prolonged or hemorrhage is
      exacerbated by long-term use of aspirin. We recommend not stopping long-term
      aspirin use before tooth extraction but enhancing hemostasis methods, if
      necessary.

PMID- 25767069
TI  - Factors affecting patient movement and re-exposure in cone beam computed
      tomography examination.
AB  - OBJECTIVE: To assess operator-, examination-, and patient-related factors,
      affecting patient movement and re-exposure in cone beam computed tomography
      (CBCT) examination. STUDY DESIGN: The sample consisted of 248 CBCT examinations
      in 190 patients video-recorded during examination. Three observers scored the
      videos; the patient moved or did not move. Operator-, examination-, and patient
      related factors were evaluated separately (chi-square test) and by multivariate
      regression analyses (patient movement and re-exposure as separate outcomes).
      RESULTS: The prevalence of movement was 21%. Cotton roll stabilizing patient's
      jaws, CBCT unit touching patient's hair, and patient's age 15 years or greater
      were related to movement. Age 15 years or greater had a significant impact on
      movement (P < .001; odds ratio [OR] 11.0). There were 16 re-exposures (6.4%). Age
      15 years or greater, presence of a cotton roll, and field of view (FOV) were
      related to re-exposure. Use of a large FOV had significant impact on re-exposure
      (P = .04; OR 5.8). CONCLUSIONS: Operator-, examination-, and patient-related
      factors may affect patient movement and re-exposure in CBCT examination.

PMID- 25767070
TI  - Competing Photocurrent Mechanisms in Quasi-Metallic Carbon Nanotube pn Devices.
AB  - Photodetectors based on quasi-metallic carbon nanotubes exhibit unique
      optoelectronic properties. Due to their small bandgap, photocurrent generation is
      possible at room temperature. The origin of this photocurrent is investigated to
      determine the underlying mechanism, which can be photothermoelectric effect or
      photovoltaic effect, depending on the bandgap magnitude of the quasi-metallic
      nanotube. 

PMID- 25767071
TI  - Development and initial validation of a damage index (DIAPS) in patients with
      thrombotic antiphospholipid syndrome (APS).
AB  - INTRODUCTION: In antiphospholipid syndrome (APS), certain principal
      manifestations are associated with a worse prognosis and organ damage. OBJECTIVE:
      The objective of this paper is to describe the development and initial content,
      criterion and construct validity of a disease-specific cumulative damage index in
      patients with thrombotic APS (DIAPS). METHODS: Through expert panel agreement, 47
      items were considered to reflect damage in APS. This preliminary version of the
      DIAPS was submitted to four local and international clinical and research experts
      in APS who ranked each item according to severity. A Delphi exercise resulted in
      a final 37 item instrument. In the second phase, a cross-sectional study was
      conducted applying the DIAPS in patients included in a multicenter electronic
      registry of patients with APS. Quality of life related to health status was
      evaluated with the EuroQol for construct validation. An alpha Cronbach and
      correlation with the EuroQol scale were calculated with SPSS 20.0 (p < 0.05).
      RESULTS: We evaluated the DIAPS in 156 patients, 77% female, with a mean age at
      diagnosis 34.7 +/- 5.5 years. A total of 69% had primary APS. Common
      comorbidities included obesity, depression and dyslipidemia. The most frequent
      manifestations resulting in sequelae were deep venous thrombosis and ischemic
      stroke. Blindness, retinal occlusive vessel disease, myocardial infarction,
      cardiac valve requiring replacement, mesenteric thrombosis, and renal
      insufficiency also occurred. Homogeneity: alpha Cronbach 0.619. DIAPS items
      correlated with EuroQol domains with the exception of pulmonary, renal,
      gastrointestinal, and endocrine systems. CONCLUSION: This study demonstrates
      content, criterion and construct validity of a new physician-reported instrument
      to assess the DIAPS. In addition, the DIAPS correlated with the EuroQol.

PMID- 25767072
TI  - The role of cytokines in the pathogenesis of cutaneous lupus erythematosus.
AB  - Cutaneous lupus erythematosus (CLE) is an inflammatory disease with a broad range
      of cutaneous manifestations that may be accompanied by systemic symptoms. The
      pathogenesis of CLE is complex, multifactorial and incompletely defined. Below we
      review the current understanding of the cytokines involved in these processes.
      Ultraviolet (UV) light plays a central role in the pathogenesis of CLE,
      triggering keratinocyte apoptosis, transport of nucleoprotein autoantigens to the
      keratinocyte cell surface and the release of inflammatory cytokines (including
      interferons (IFNs), tumor necrosis factor (TNF)-alpha, interleukin (IL)-1, IL-6,
      IL-8, IL-10 and IL-17). Increased IFN, particularly type I IFN, is central to the
      development of CLE lesions. In CLE, type I IFN is produced in response to nuclear
      antigens, immune complexes and UV light. Type I IFN increases leukocyte
      recruitment to the skin via inflammatory cytokines, chemokines, and adhesion
      molecules, thereby inducing a cycle of cutaneous inflammation. Increased TNFalpha
      in CLE may also cause inflammation. However, decreasing TNFalpha with an anti
      TNFalpha agent can induce CLE-like lesions. TNFalpha regulates B cells, increases
      the production of inflammatory molecules and inhibits the production of IFN
      alpha. An increase in the inflammatory cytokines IL-1, IL-6, IL-10, IL-17 and IL
      18 and a decrease in the anti-inflammatory cytokine IL-12 also act to amplify
      inflammation in CLE. Specific gene mutations may increase the levels of these
      inflammatory cytokines in some CLE patients. New drugs targeting various aspects
      of these cytokine pathways are being developed to treat CLE and systemic lupus
      erythematosus (SLE). 

PMID- 25767073
TI  - Emerging roles for scavenger receptor SREC-I in immunity.
AB  - SREC-I is a class F scavenger receptor with key role in the immune response,
      particularly in antigen presenting cell (APC) such as macrophages and dendritic
      cells (DC). This receptor is able to mediate engulfment of dead cells as well as
      endocytosis of heat shock protein (HSP)-antigen complexes. SREC-I could thus
      potentially mediate the tolerizing influence of apoptotic cells or the
      immunostimulatory effects of HSP-peptide complexes, depending on context. This
      receptor was able to mediate presentation of external antigens, bound to HSPs
      through both the class II pathway as well as cross presentation via MHC class I
      complexes. In addition to its recently established role in adaptive immunity,
      emerging studies are indicating a broad role in innate immunity and regulation of
      cell signaling through Toll Like Receptors (TLR). SREC-I may thus play a key role
      in APC function by coordinating immune responses to internal and external
      antigens in APC. 

PMID- 25767075
TI  - Direct conversion of human fibroblasts into dopaminergic neural progenitor-like
      cells using TAT-mediated protein transduction of recombinant factors.
AB  - Recent progress in the generation of induced neural progenitor cells (iNPCs)
      holds tremendous potential for regenerative medicine. However, a major limitation
      is the lack of a reliable source for cell replacement therapy in neurological
      diseases such as Parkinson's disease (PD). Here, we show that the combination of
      small molecules (SM) and TAT-mediated protein transduction of SOX2 and LMX1a in a
      3D sphere culture directly convert human fibroblasts to induced dopaminergic
      neural progenitor-like cells (iDPCs). The generated iDPCs expressed various NPC
      markers (SOX2, PAX6, NESTIN, OLIG2) and midbrain progenitor markers (EN1, LMX1a,
      FOXA2, WNT1) as detected by immunostaining and real-time PCR. Following
      differentiation, the majority of cells expressed neuronal dopaminergic markers as
      indicated by co-expression of TH with NURR1, and/or PITX3. We found that SOX2 and
      LMX1a TAT-mediated protein transduction in the combination of SM could directly
      convert human fibroblasts to self-renewal iDPCs. In conclusion, to our best
      knowledge, this is the first report of generation of safe DPCs and may suggest an
      alternative strategy for cell therapy for the treatment of neurodegenerative
      disorders. 

PMID- 25767074
TI  - Inhibitory effect of cucurbitacin B on imiquimod-induced skin inflammation.
AB  - Psoriasis is a common skin disease, of which pathogenesis involves the increase
      of inflammatory reaction in epidermal cells. In an attempt to find therapeutics
      for psoriasis, we found that cucurbitacin B has an inhibitory potential on
      imiquimod-induced inflammation of keratinocytes. Cucurbitacin B significantly
      inhibited imiquimod-induced expression of crucial psoriatic cytokines, such as IL
      8 and CCL20, via down-regulation of NF-kappaB and STAT3 signaling pathway in
      human keratinocytes. In addition, keratinocyte proliferation was markedly
      inhibited by cucurbitacin B. The potential beneficial effect of cucurbitacin B on
      psoriasis was further validated in imiquimod-induced psoriasiform dermatitis of
      experimental animal. Topical application of cucurbitacin B resulted in
      significant reduction of epidermal hyperplasia and inflammatory cytokines
      production, and ameliorated the psoriatic symptom. Taken together, these results
      suggest that cucurbitacin B may be a potential candidate for the treatment of
      psoriasis. 

PMID- 25767076
TI  - Oxaliplatin triggers necrosis as well as apoptosis in gastric cancer SGC-7901
      cells.
AB  - Intrinsic apoptotic pathway is considered to be responsible for cell death
      induced by platinum anticancer drugs. While in this study, we found that,
      necrosis is an indispensable pathway besides apoptosis in oxaliplatin-treated
      gastric cancer SGC-7901 cells. Upon exposure to oxaliplatin, both apoptotic and
      necrotic features were observed. The majority of dead cells were double positive
      for Annexin V and propidium iodide (PI). Moreover, mitochondrial membrane
      potential collapsed and caspase cascades were activated. However, ultrastructural
      changes under transmission electron microscope, coupled with the release of
      cellular contents, demonstrated the rupture of the plasma membrane. Oxaliplatin
      administration did not stimulate reactive oxygen species (ROS) production and
      autophagy, but elevated the protein level of Bmf. In addition, receptor
      interacting protein 1 (RIP1), but not receptor interacting protein 3 (RIP3) and
      its downstream components participated in this death process. Necrostatin-1 (Nec
      1) blocked oxaliplatin-induced cell death nearly completely, whereas z-VAD-fmk
      could partially suppress cell death. Oxaliplatin treatment resulted in poly(ADP
      ribose) polymerase-1 (PARP-1) overactivation, as indicated by the increase of
      poly(ADP-ribose) (PAR), which led to NAD(+) and ATP depletion. PARP-1 inhibitor,
      olaparib, could significantly block oxaliplatin-induced cell death, thus
      confirming that PARP-1 activation is mainly responsible for the cytotoxicity of
      oxaliplatin. Phosphorylation of H2AX at Ser139 and translocalization of apoptosis
      inducing factor (AIF) are critical for this death process. Taken together, these
      results indicate that oxaliplatin can bypass canonical cell death pathways to
      kill gastric cancer cells, which may be of therapeutic advantage in the treatment
      of gastric cancer. 

PMID- 25767077
TI  - Up-regulation of megakaryocytic Na(+)/Ca(2+) exchange in klotho-deficient mice.
AB  - The active form of vitamin D, 1,25(OH)2D3, is a powerful regulator of cytosolic
      Ca(2+)-concentration ([Ca(2+)]i) in a variety of cell types. The formation of
      1,25(OH)2D3 is inhibited by FGF23, an effect requiring presence of klotho.
      1,25(OH)2D3 plasma levels are excessive in klotho-deficient mice (kl/kl). A
      previous study revealed that klotho-deficiency is followed by decreased
      activation of platelets, an effect at least in part due to blunted store operated
      Ca(2+) entry (SOCE). In other cell types 1,25(OH)2D3 has been shown to up
      regulate the Na(+)/Ca(2+)-exchanger, which could, depending on cell membrane
      potential and cytosolic Na(+) concentration, either decrease or increase
      [Ca(2+)]i. The present study explored whether Na(+)/Ca(2+)-exchanger activity is
      different in megakaryocytes isolated from kl/kl mice than in megakaryocytes
      isolated from wild type mice. Na(+)/Ca(2+)-exchanger induced currents were
      determined by whole cell patch clamp and the Na(+)/Ca(2+)-exchanger induced
      alterations of [Ca(2+)]i by Fura-2 fluorescence. As a result, the inward current
      and the increase of [Ca(2+)]i following replacement of extracellular Na(+) by
      NMDG were higher in kl/kl megakaryocytes than in wild type megakaryocytes, a
      difference abrogated by treatment of the mice with low Vitamin D diet.
      Pretreatment of wild type megakaryocytes with 1,25(OH)2D3 (100 nM, 48 h) was
      followed by enhancement of both, inward current and increase of [Ca(2+)]i
      following replacement of extracellular Na(+) by NMDG. In conclusion, the present
      observations reveal a powerful stimulating effect of 1,25(OH)2D3 on Na(+)/Ca(2+)
      exchanger activity in megakaryocytes.

PMID- 25767078
TI  - Improving litter size by boar spermatozoa: application of combined H33258/CTC
      staining in field trial with artificial insemination.
AB  - Conventional semen analysis offers basic information on infertility; however, its
      clinical value in predicting fertility status is unclear. To establish an
      accurate diagnosis of male fertility, semen analysis under capacitation condition
      is necessary because only capacitated spermatozoa are capable of fertilizing
      oocytes. The objective of this study was to verify male fertility based on
      conventional semen analysis before and after capacitation, including the
      assessment of motility (%), motion kinematics, and capacitation status of
      spermatozoa. A computer-assisted sperm analysis system and chlortetracycline
      staining were applied to evaluate the motility parameters and capacitation
      status, respectively. To enable efficacy of the two methods for predicting
      fertility, correlation analysis was performed with the historic litter size. Our
      results showed that sperm motility (%), motion kinematics, and their variations
      before and after capacitation represented a statistical non-significant
      correlation with litter size. Litter size showed significant correlation with
      acrosome reaction (AR) after capacitation (r = 0.375), as well as differences
      (Delta) in AR (r = 0.333) and capacitated (B) pattern (r = -0.447) before and
      after capacitation. The overall accuracy of the assay for predicting litter sizes
      using the AR and differences (Delta) in the AR and B pattern was 70%. On the
      basis of these results, we propose that capacitation status of spermatozoa is a
      more reliable indicator for evaluating male fertility status compared to motility
      parameters. Therefore, we suggest that analysis of capacitation status in company
      with conventional semen analysis may accept to evaluate more accurate diagnosis
      or prognosis of male fertility.

PMID- 25767080
TI  - A concise synthetic approach to brazilin via Pd-catalyzed allylic arylation.
AB  - A short synthetic route to the trimethyl ether of brazilin was developed in 6
      steps from 7-methoxychromene with 78% overall yield. Regioselective installation
      of a formyl group onto 7-methoxychromene followed by reduction and acetylation
      afforded allylic acetate. Palladium-catalyzed allylic coupling of allylic acetate
      with arylboronic acid provided direct access to 3-benzylchromene which was
      converted to the target molecule upon ensuing dihydroxylation and acid-catalyzed
      cyclization in a highly concise manner. 

PMID- 25767081
TI  - Energy band alignment in chalcogenide thin film solar cells from photoelectron
      spectroscopy.
AB  - Energy band alignment plays an important role in thin film solar cells. This
      article presents an overview of the energy band alignment in chalcogenide thin
      film solar cells with a particular focus on the commercially available material
      systems CdTe and Cu(In,Ga)Se2. Experimental results from two decades of
      photoelectron spectroscopy experiments are compared with density functional
      theory calculations taken from literature. It is found that the experimentally
      determined energy band alignment is in good agreement with theoretical
      predictions for many interfaces. These alignments, in particular the
      theoretically predicted alignments, can therefore be considered as the intrinsic
      or natural alignments for a given material combination. The good agreement
      between experiment and theory enables a detailed discussion of the interfacial
      composition of Cu(In,Ga)Se2/CdS interfaces in terms of the contribution of
      ordered vacancy compounds to the alignment of the energy bands. It is furthermore
      shown that the most important interfaces in chalcogenide thin film solar cells,
      those between Cu(In,Ga)Se2 and CdS and between CdS and CdTe are quite insensitive
      to the processing of the layers. There are plenty of examples where a significant
      deviation between experimentally-determined band alignment and theoretical
      predictions are evident. In such cases a variation of band alignment of sometimes
      more than 1 eV depending on interface preparation can be obtained. This variation
      can lead to a significant deterioration of device properties. It is suggested
      that these modifications are related to the presence of high defect
      concentrations in the materials forming the contact. The particular defect
      chemistry of chalcogenide semiconductors, which is related to the ionicity of the
      chemical bond in these materials and which can be beneficial for material and
      device properties, can therefore cause significant device limitations, as e.g. in
      the case of the CuInS2 thin film solar cells or for new chalcogenide absorber
      materials.

PMID- 25767079
TI  - Risk factors for neurodegeneration in idiopathic rapid eye movement sleep
      behavior disorder: a multicenter study.
AB  - OBJECTIVE: To assess whether risk factors for Parkinson disease and dementia with
      Lewy bodies increase rate of defined neurodegenerative disease in idiopathic
      rapid eye movement (REM) sleep behavior disorder (RBD). METHODS: Twelve centers
      administered a detailed questionnaire assessing risk factors for
      neurodegenerative synucleinopathy to patients with idiopathic RBD. Variables
      included demographics, lifestyle factors, pesticide exposures, occupation,
      comorbid conditions, medication use, family history, and autonomic/motor
      symptoms. After 4 years of follow-up, patients were assessed for dementia or
      parkinsonism. Disease risk was assessed with Kaplan-Meier analysis, and
      epidemiologic variables were compared between convertors and those still
      idiopathic using logistic regression. RESULTS: Of 305 patients, follow-up
      information was available for 279, of whom 93 (33.3%) developed defined
      neurodegenerative disease. Disease risk was 25% at 3 years and 41% after 5 years.
      Patients who converted were older (difference = 4.5 years, p < 0.001), with
      similar sex distribution. Neither caffeine, smoking, nor alcohol exposure
      predicted conversion. Although occupation was similar between groups, those who
      converted had a lower likelihood of pesticide exposure (occupational insecticide
      = 2.3% vs 9.0%). Convertors were more likely to report family history of dementia
      (odds ratio [OR] = 2.09), without significant differences in Parkinson disease or
      sleep disorders. Medication exposures and medical history were similar between
      groups. Autonomic and motor symptoms were more common among those who converted.
      Risk factors for primary dementia and parkinsonism were generally similar, except
      for a notably higher clonazepam use in dementia convertors (OR = 2.6).
      INTERPRETATION: Patients with idiopathic RBD are at very high risk of
      neurodegenerative synucleinopathy. Risk factor profiles between convertors and
      nonconvertors have both important commonalities and differences.

PMID- 25767082
TI  - Ketamine: promising path or false prophecy in the development of novel
      therapeutics for mood disorders?

PMID- 25767083
TI  - Postmortem brain: an underutilized substrate for studying severe mental illness.

PMID- 25767084
TI  - Ruthenium complexes with dendritic ferrocenyl phosphanes: synthesis,
      characterization, and application in the catalytic redox isomerization of allylic
      alcohols.
AB  - An efficient system for the catalytic redox isomerization of the allylic alcohol
      1-octen-3-ol to 3-octanone is presented. The homogeneous ruthenium(II) catalyst
      contains a monodentate phosphane ligand with a ferrocene moiety in the backbone
      and provides 3-octanone in quantitative yields. The activity is increased by
      nearly 90 % with respect to the corresponding triphenyl phosphane ruthenium(II)
      complex. By grafting the catalyst at the surface of a dendrimer, the catalytic
      activity is further increased. By introducing different spacers between ferrocene
      and phosphorus, the influence on the electronic properties of the complexes is
      shown by evaluating the electrochemical behavior of the compounds.

PMID- 25767085
TI  - Remodelling of cardiac sympathetic re-innervation with thoracic spinal cord
      stimulation improves left ventricular function in a porcine model of heart
      failure.
AB  - AIMS: Thoracic spinal cord stimulation (SCS) has been shown to improve left
      ventricular ejection fraction (LVEF) in heart failure (HF). Nevertheless, the
      optimal duration (intermittent vs. continuous) of stimulation and the mechanisms
      of action remain unclear. METHODS AND RESULTS: We performed chronic thoracic SCS
      at the level of T1-T3 (50 Hz, pulse width 0.2 ms) in 30 adult pigs with HF
      induced by myocardial infarction and rapid ventricular pacing for 4 weeks. All
      the animals were treated with daily oral metoprolol succinate (25 mg) plus
      ramipril (2.5 mg), and randomized to a control group (n = 10), intermittent SCS
      (4 h *3, n = 10) or continuous SCS (24 h, n = 10) for 10 weeks. Serial
      measurements of LVEF and +dP/dt and serum levels of norepinephrine and B-type
      natriuretic peptide (BNP) were measured. After sacrifice, immunohistological
      studies of myocardial sympathetic and parasympathetic nerve sprouting and
      innervation were performed. Echocardiogram revealed a significant increase in
      LVEF and +dP/dt at 10 weeks in both the intermittent and continuous SCS group
      compared with controls (P < 0.05). In both SCS groups, there was diffuse
      sympathetic nerve sprouting over the infarct, peri-infarct, and normal regions
      compared with only the peri-infarct and infarct regions in the control group. In
      addition, sympathetic innervation at the peri-infarct and infarct regions was
      increased following SCS, but decreased in the control group. Myocardium
      norepinephrine spillover and serum BNP at 10 weeks was significantly decreased
      only in the continuous SCS group (P < 0.05). CONCLUSIONS: In a porcine model of
      HF, SCS induces significant remodelling of cardiac sympathetic innervation over
      the peri-infarct and infarct regions and is associated with improved LV function
      and reduced myocardial norepinephrine spillover.

PMID- 25767087
TI  - Anatomical variations of the coronary sinus valve (Thebesian valve): implications
      for electrocardiological procedures.
AB  - AIMS: The Thebesian valve (TV) can be a significant obstacle to coronary sinus
      (CS) cannulation. The aim of this study was to evaluate the characteristic
      features of the CS valve--TV anatomy. In particular, emphasis was placed on
      identifying specific structures of the TV that could potentially complicate CS
      cannulation. METHODS AND RESULTS: We examined 273 autopsied human hearts. The
      height of the TV and the diameter of the CS were measured. The valves were
      classified according to their shape into five types: remnant, semilunar, fold,
      cord, and mesh and fenestrated. The mean transverse CS ostium (CSO) diameter was
      12.2 +/- 3.5 mm. The TV was present in 224 (82.1%) cases. The most common type of
      TV was semilunar: 32.6%; followed by remnant: 25.5%; fold: 17.4%; cord: 14.3%;
      and lastly mesh and fenestrated: 10.3%. The mean TV height for remnant-semilunar
      fold types was 5.8 +/- 3.0 mm. In seven cases, the present TV (2.6%) covered the
      entire orifice of the CS. Hearts with larger CSO diameter had lower TV height (P
      < 0.001). CONCLUSIONS: We propose a new classification of the TV shapes based on
      the largest sample to date. We assessed that only in 2.6% of all 273 cases the
      presence of an obstructive TV can cause unsuccessful cannulation. The height of
      the TV was inversely correlated to the CSO diameter (r = -0.33; P < 0.001).

PMID- 25767086
TI  - Pulmonary embolism in patients with transvenous cardiac implantable electronic
      device leads.
AB  - BACKGROUND: Cardiac implantable electronic devices (CIEDs) are commonly
      associated with transvenous lead-related thrombi that can cause pulmonary
      embolism (PE). METHODS AND RESULTS: We retrospectively evaluated all patients
      with transvenous CIED leads implanted at Mayo Clinic Rochester between 1 January
      2000, and 25 October 2010. Pulmonary embolism outcomes during follow-up were
      screened using diagnosis codes and confirmed with imaging study reports. Of 5646
      CIED patients (age 67.3 +/- 16.3 years, 64% men, mean follow-up 4.69 years) 88
      developed PE (1.6%), incidence 3.32 [95% confidence interval (CI) 2.68-4.07] per
      1000 person-years [men: 3.04 (95% CI 2.29-3.96) per 1000 person-years; women:
      3.81 (95% CI 2.72-5.20) per 1000 person-years]. Other than transvenous CIED
      lead(s), 84% had another established risk factor for PE such as deep vein
      thrombosis (28%), recent surgery (27%), malignancy (25%), or prior history of
      venous thromboembolism (15%). At the time of PE, 22% had been hospitalized for >=
      48 h, and 59% had been hospitalized in the preceding 30 days. Pulmonary embolism
      occurred in 22% despite being on systemic anticoagulation therapy. Out of 88
      patients with PE, 45 subsequently died, mortality rate 93 (95% CI 67-123) per
      1000 person-years (hazard ratio 2.0, 95% CI 1.5-2.7, P < 0.0001). CONCLUSIONS:
      Though lead-related thrombus is commonly seen in patients with transvenous CIED
      leads, clinical PE occurs with a low incidence. It is possible that embolism of
      lead thrombus is uncommon or emboli are too small to cause consequential
      pulmonary infarction.

PMID- 25767088
TI  - Contrast-enhanced magnetic resonance imaging in carbamazepine-induced aseptic
      meningitis.

PMID- 25767089
TI  - Quantum dynamical simulation of photoinduced electron transfer processes in dye
      semiconductor systems: theory and application to coumarin 343 at TiO2.
AB  - A recently developed methodology to simulate photoinduced electron transfer
      processes at dye-semiconductor interfaces is outlined. The methodology employs a
      first-principles-based model Hamiltonian and accurate quantum dynamics
      simulations using the multilayer multiconfiguration time-dependent Hartree
      approach. This method is applied to study electron injection in the dye
      semiconductor system coumarin 343-TiO2. Specifically, the influence of electronic
      vibrational coupling is analyzed. Extending previous work, we consider the
      influence of Dushinsky rotation of the normal modes as well as anharmonicities of
      the potential energy surfaces on the electron transfer dynamics. 

PMID- 25767090
TI  - Rural West has highest rate of cold related deaths in US, CDC report shows.

PMID- 25767091
TI  - Nurse practitioner graduates "Speak Out" about the adequacy of their educational
      preparation to care for older adults: A qualitative study.
AB  - PURPOSE: With a shortage of primary care providers prepared to care for an aging
      U.S. population, nurse practitioner (NP) programs are integrating gerontological
      content. This qualitative descriptive study explored NP graduate perceptions on
      the adequacy of their education to prepare them to care for seniors. METHODS:
      Twenty-three graduates of NP program options at two universities in the western
      U.S. participated in focus group discussions or interviews. Participants shared
      their perceptions of their NP educational preparation and suggestions for
      enhancing gerontologic curriculum. CONCLUSIONS: Four main domains emerged from
      analysis of qualitative data: (a) "Getting your boots on and getting into the
      role"; (b) "Older people are more complex than we were prepared to care for"; (c)
      "It is very different as a provider, but I am so glad I was a nurse with
      experience first"; (d) "NPs have a scope of practice, physician assistants (PAs)
      have a job description-but I wish we had their [procedural] preparation."
      IMPLICATIONS FOR PRACTICE: Graduates identified a need for more educational
      content and clinical experiences specific to the care of older adults. Some
      suggested a postgraduate residency or mentoring option to assist NP role
      transition and progression and limit role confusion.

PMID- 25767092
TI  - Hyaluronic acid injections protect patellar tendon from detraining-associated
      damage.
AB  - INTRODUCTION: Having previously demonstrated that detraining affects patellar
      tendon (PT) proteoglycan content and collagen fiber organization, we undertook
      the present study with two aims: to improve knowledge on the adaptation of PT and
      its enthesis to detraining from a histological and histomorphometric point of
      view, and to investigate the hypothesis that repeated peri-patellar injections of
      hyaluronic acid (HA) on detrained PT may reduce and limit detrained associated
      damage. METHODS: Twenty-four male Sprague-Dawley rats were divided into 3 groups:
      Untrained (n=6), Trained (n=6) (10 wks-treadmill) and Detrained (n=12). In the
      detrained rats, the left tendon was untreated while the right tendon received
      repeated peri-patellar injections of either HA or saline (NaCl). Structure and
      morphology of PTs (modified Movin score, tear density, collagen type I and III)
      and enthesis (cell morphology, chondrocyte cluster formation, tidemark integrity,
      matrix staining and vascularization) were evaluated. RESULTS: The left PT and
      enthesis of the Detrained groups showed altered structure and morphology with the
      highest Movin score values, the highest percentage of collagen III and the lowest
      of collagen I; the lowest score values were observed in the Trained and Detrained
      HA groups. Detrained-NaCl PTs showed the highest collagen III and the lowest
      collagen I values with respect to Detrained-HA PTs. CONCLUSION: This study
      strengthens previously published data showing the alteration in tendon and
      enthesis morphology due to discontinuation of training, and provides new data
      showing that treatment with HA is effective in the maintenance of the structural
      properties of PT and enthesis in Detrained rats. Such beneficial effects could
      play a significant role in the management of conservative and rehabilitation
      strategies in athletes that change type, intensity and duration of training.

PMID- 25767093
TI  - Using psychophysics to ask if the brain samples or maximizes.
AB  - The two-alternative forced-choice (2AFC) task is the workhorse of psychophysics
      and is used to measure the just-noticeable difference, generally assumed to
      accurately quantify sensory precision. However, this assumption is not true for
      all mechanisms of decision making. Here we derive the behavioral predictions for
      two popular mechanisms, sampling and maximum a posteriori, and examine how they
      affect the outcome of the 2AFC task. These predictions are used in a combined
      visual 2AFC and estimation experiment. Our results strongly suggest that subjects
      use a maximum a posteriori mechanism. Further, our derivations and experimental
      paradigm establish the already standard 2AFC task as a behavioral tool for
      measuring how humans make decisions under uncertainty. 

PMID- 25767094
TI  - How people achieve their amazing temporal precision in interception.
AB  - People can hit rapidly moving balls with amazing precision. To determine how they
      manage to do so, we explored how various factors that we could manipulate
      influenced people's precision when intercepting virtual targets. We found that
      temporal precision was highest for fast targets that subjects were free to
      intercept wherever they wished. Temporal precision was much poorer when the point
      of interception was specified in advance. Examining responses to abrupt
      perturbations of the target's motion revealed that people adjusted where rather
      than when they would hit the target if given the choice. A model that combines
      judging how long it will take to reach the target's path with estimating the
      target's position at that time from its visually perceived position and velocity
      could account for the observed precision with reasonable values for all the
      parameters. The model considers all relevant sources of errors, together with the
      delays with which the various aspects can be adjusted. Our analysis provides a
      biologically plausible explanation for how light falling on the eye can guide the
      hand to intercept a moving ball with such high precision. 

PMID- 25767096
TI  - Stop trying to integrate organisations.

PMID- 25767095
TI  - Walking, biking or sport: how Spanish women attending breast cancer screening
      meet physical activity recommendations?
AB  - BACKGROUND: The aim is to analyse physical activity (PA), the fulfillment
      recommendation of at least 150 min of moderate PA, through walking/biking (W&B),
      sport, both types of PA and the factors associated with inactivity by Spanish
      women who attended breast cancer screening programmes. METHODS: The DDM-Spain is
      a multicentre cross-sectional study involving 3584 women, aged 45-68, attending
      screening in seven Spanish cities. Data were collected using a questionnaire,
      including age, socio-demographic and lifestyle characteristics, family burden and
      PA. PA was converted into metabolic equivalent of task (METs), categorized as low
      <= 600 METs min per week (m/w), moderate 600-3000 METs m/w and high >= 3000 METs
      m/w. A multivariate logistic regression was performed to identify variables
      associated with inactivity for each type of PA. RESULTS: No women achieved a high
      level of PA through sport. 79.2% achieved a high or moderate level of PA by W&B.
      Lack of sport was associated with being overweight (odds ratio OR = 1.31; 95%
      confidence interval CI: 1.06 to 1.62), body mass index (BMI) >= 30 (OR = 1.85;
      95% CI: 1.44 to 2.38), smoking (OR = 1.56; 95% CI: 1.22 to 2.00) and living with
      a disabled person (OR = 1.64; 95% CI: 1.0 to 2.81), whereas enough sport practice
      was associated with higher educational or socio-economic level (SEL). Regarding
      W&B, inactivity was associated with BMI >= 30 (OR = 1.91; 95% CI: 1.49 to 2.45)
      and living with someone >74 (OR = 1.96; 95% CI: 1.48 to 2.58). Inactivity for
      both types of exercise was associated with a BMI >= 30 (OR = 2.13; 95% CI: 1.63
      to 2.8), smoking (OR = 1.41; 95% CI: 1.09 to 1.81) and living with someone >74
      (OR = 1.69; 95% CI: 1.24 to 2.28). CONCLUSIONS: Family burden and BMI >= 30 are
      inversely associated with both types of PA. W&B is the most common type of PA
      regardless of educational and SEL.

PMID- 25767097
TI  - Searching for new TiO2 crystal phases with better photoactivity.
AB  - Using the recently developed stochastic surface walking global optimization
      method, this work explores the potential energy surface of TiO2 crystals aiming
      to search for likely phases with higher photocatalytic activity. Five new phases
      of TiO2 are identified and the lowest energy phase transition pathways connecting
      to the most abundant phases (rutile and anatase) are determined. Theory shows
      that a high-pressure phase, alpha-PbO2-like form (TiO2II) acts as the key
      intermediate in between rutile and anatase. The phase transition of anatase to
      rutile belongs to the diffusionless Martensitic phase transition, occurring
      through a set of habit planes, rutile(101)//TiO2II(001), and
      TiO2II(100)//anatase(112). With regard to the photocatalytic activity, three pure
      phases (#110, pyrite and fluorite) are found to possess the band gap narrower
      than rutile, but they are unstable at the low-pressure condition. Instead, a
      mixed anatase-TiO2II phase is found to have good stability and narrower band gap
      than both parent phases. Because of the phase separation, the mixed phase is also
      expected to improve the photocatalytic performance by reducing the probability of
      the electron-hole pair recombination. 

PMID- 25767099
TI  - Reply to Robinson and Brown: It is the combination of ERAP1 allotypes that
      identifies individuals with Ankylosing Spondylitis.

PMID- 25767098
TI  - STAT3-driven transcription depends upon the dimethylation of K49 by EZH2.
AB  - Several transcription factors, including p53, NF-kappaB, and STAT3, are modified
      by the same enzymes that also modify histones, with important functional
      consequences. We have identified a previously unrecognized dimethylation of K49
      of STAT3 that is crucial for the expression of many IL-6-dependent genes,
      catalyzed by the histone-modifying enzyme enhancer of zeste homolog 2 (EZH2).
      Loss of EZH2 is protumorigenic in leukemias, but its overexpression is
      protumorigenic in solid cancers. Connecting EZH2 to a functionally important
      methylation of STAT3, which is constitutively activated in many tumors, may help
      reveal the basis of the opposing roles of EZH2 in liquid and solid tumors and
      also may identify novel therapeutic opportunities. 

PMID- 25767100
TI  - ERAP1 biology and assessment in Ankylosing Spondylitis.

PMID- 25767101
TI  - Modeling the surface photovoltage of silicon slabs with varying thickness.
AB  - The variation with thickness of the energy band gap and photovoltage at the
      surface of a thin semiconductor film are of great interest in connection with
      their surface electronic structure and optical properties. In this work, the
      change of a surface photovoltage (SPV) with the number of layers of a crystalline
      silicon slab is extracted from models based on their atomic structure. Electronic
      properties of photoexcited slabs are investigated using generalized gradient and
      hybrid density functionals, and plane wave basis sets. Si(1 1 1) surfaces have
      been terminated by hydrogen atoms to compensate for dangling bonds and have been
      described by large supercells with periodic boundary conditions. Calculations of
      the SPV of the Si slabs have been done in terms of the reduced density matrix of
      the photoactive electrons including dissipative effects due to their interaction
      with medium phonons and excitons. Surface photovoltages have been calculated for
      model Si slabs with 4-12, and 16 layers, to determine convergence trends versus
      slab thickness. Band gaps and the inverse of the SPVs have been found to scale
      nearly linearly with the inverse thickness of the slab, while the electronic
      density of states increases quadratically with thickness. Our calculations show
      the same trends as experimental values indicating band gap reduction and
      absorption enhancement for Si films of increasing thickness. Simple arguments on
      confined electronic structures have been used to explain the main effects of
      changes with slab thickness. A procedure involving shifted electron excitation
      energies is described to improve results from generalized gradient functionals so
      they can be in better agreement with the more accurate but also more computer
      intensive values from screened exchange hybrid functionals.

PMID- 25767102
TI  - Trigeminal neuralgia.

PMID- 25767103
TI  - Barrett's Oesophagus Surveillance versus endoscopy at need Study (BOSS): protocol
      and analysis plan for a multicentre randomized controlled trial.
AB  - OBJECTIVES: The absolute annual risk of patients with Barrett's oesophagus (BO)
      developing oesophageal adenocarcinoma (OAC) is <= 0.5%. Screening BO patients for
      malignant progression using endoscopic surveillance is widely practised. To
      assess the efficacy and cost-effectiveness of this, we developed a protocol for a
      randomized controlled trial of surveillance versus 'at need' endoscopy. METHODS:
      In a multicentre trial, 3400 BO patients randomized to either 2-yearly endoscopic
      surveillance or 'at need' endoscopy will be followed up for 10 years. Urgent
      endoscopy will be offered to all patients who develop symptoms of dysphagia,
      unexplained weight loss > 7lb (3.2 kg), iron deficiency anaemia, recurrent
      vomiting, or worsening upper gastrointestinal symptoms. Participants must have
      endoscopically and histologically confirmed BO, with circumferential BO >= 1 cm
      or maximal tongue/island length >= 2 cm. Candidates with existing oesophageal
      high-grade dysplasia or cancer, or previous upper gastrointestinal cancer will be
      excluded. Primary outcome will be overall survival. Secondary outcomes will be
      cost effectiveness (cost per life year saved and quality adjusted life years);
      cancer-specific survival; time to OAC diagnosis and stage at diagnosis; morbidity
      and mortality related to any interventions; and frequency of endoscopy.
      CONCLUSIONS: This randomized trial will provide data to evaluate the efficacy and
      cost-effectiveness of screening BO patients for OAC.

PMID- 25767104
TI  - A note on the design of cancer screening trials.
AB  - OBJECTIVES: To investigate the consequences of different cancer screening trial
      designs and follow-up options for accuracy of the estimate of the effect of
      screening on disease-specific mortality. METHODS: We consider a randomized trial
      of breast cancer screening with a screening phase in which the intervention group
      is offered screening and the control group is not, and optional further follow-up
      after this screening phase. Postulating a lead time effect similar to that
      observed in breast cancer screening trials, we calculate the observed relative
      risk of disease-specific mortality and compare this with the true relative risk,
      for four design options: (1) no follow-up beyond the screening phase, ie. the
      screening phase and the observation period are identical; (2) follow-up
      continuing beyond the screening phase, all cancer-specific deaths counted,
      including those diagnosed after the screening phase; (3) follow-up continuing
      beyond the screening phase, but with only deaths from cancers diagnosed during
      the screening phase included; and (4) follow-up continuing beyond the screening
      phase, a single screen of the control group conducted at the end of the screening
      phase, and only deaths from cancers diagnosed during the screening phase in both
      arms up to completion of the single control screen included. RESULTS: All designs
      in which follow-up for mortality continues beyond the screening phase incurred a
      bias against screening. The design in which the control group undergoes a single
      screen at the end of the screening phase was least biased in the example used.
      CONCLUSIONS: The expedient of a single screen of the control group at the end of
      the screening phase has acceptable accuracy, but is still slightly conservatively
      biased.

PMID- 25767105
TI  - Linker dependence of interfacial electron transfer rates in Fe(II)-polypyridine
      sensitized solar cells.
AB  - Dye-sensitized solar cells (DSSCs) convert solar energy to electricity employing
      dye molecules attached to a semiconductor surface. Some of the most efficient
      DSSCs use Ru-based chromophores. Fe-based dyes represent a cheaper and more
      environmentally friendly alternative to these expensive and toxic dyes. The
      photoactive state of Fe-based chromophores responsible for charge-separation at
      the dye-semiconductor interface is, however, deactivated on a sub-picosecond time
      scale via the intersystem crossing (ISC) into a manifold of low-lying photo
      inactive quintet states. Therefore, development of Fe-based dyes capable of fast
      interfacial electron transfer (IET) leading to efficient charge separation on a
      time scale competitive with the ISC events is important. This work investigates
      how linker groups anchoring a prototypical Fe-based dye [Fe(bpy-L)2(CN)2] (bpy =
      2,2'-bipyridine, L = linker group) onto the TiO2 semiconductor surface influence
      the IET rates in the dye-semiconductor assemblies. Linker groups investigated
      include carboxylic acid, phosphonic acid, hydroxamate, catechol, and
      acetylacetonate. We employ time-dependent density functional theory (TD-DFT) to
      obtain absorption spectra of [Fe(bpy-L)2(CN)2] with each linker, and quantum
      dynamics simulations to investigate the IET rates between the dye and the (101)
      TiO2 anatase surface. For all attachments, TD-DFT calculations show similar
      absorption spectra with two main bands corresponding to the metal-to-ligand
      charge transfer transitions. The quantum dynamics simulations predict that the
      utilization of the hydroxamate linker instead of the commonly used carboxylic
      acid linker will lead to a more efficient IET and better photon-to-current
      conversion efficiencies in Fe(II)-polypyridine sensitized solar cells. 

PMID- 25767106
TI  - Africa launches forum to promote scientific research excellence.

PMID- 25767107
TI  - Coupled quantum-classical method for long range charge transfer: relevance of the
      nuclear motion to the quantum electron dynamics.
AB  - Charge and excitonic-energy transfer phenomena are fundamental for energy
      conversion in solar cells as well as artificial photosynthesis. Currently, much
      interest is being paid to light-harvesting and energy transduction processes in
      supramolecular structures, where nuclear dynamics has a major influence on
      electronic quantum dynamics. For this reason, the simulation of long range
      electron transfer in supramolecular structures, under environmental conditions
      described within an atomistic framework, has been a difficult problem to study.
      This work describes a coupled quantum mechanics/molecular mechanics method that
      aims at describing long range charge transfer processes in supramolecular
      systems, taking into account the atomistic details of large molecular structures,
      the underlying nuclear motion, and environmental effects. The method is applied
      to investigate the relevance of electron-nuclei interaction on the mechanisms for
      photo-induced electron-hole pair separation in dye-sensitized interfaces as well
      as electronic dynamics in molecular structures. 

PMID- 25767108
TI  - Expression of the Yersinia enterocolitica O:3 LPS O-antigen and outer core gene
      clusters is RfaH-dependent.
AB  - The antiterminator RfaH is required for the expression of LPS, capsule,
      haemolysin, exotoxin, haemin uptake receptor and F pilus. As these structures are
      critical for bacterial virulence, loss of RfaH usually leads to attenuation.
      Here, we inactivated the rfaH gene of Yersinia enterocolitica O:3 to study its
      role in this enteropathogen. RNA sequencing of the WT and DeltarfaH strain
      transcriptomes revealed that RfaH acted as a highly specific regulator that
      enhanced the transcription of the operons involved in biosynthesis of LPS O
      antigen and outer core (OC), but did not affect the expression of enterobacterial
      common antigen. Interestingly, the transcriptome of the DeltarfaH strain was very
      similar to that of an O-antigen-negative mutant. This indicated that some of the
      changes seen in the DeltarfaH strain, such as the genes involved in outer
      membrane homeostasis or in the stress-response-associated Cpx pathway, were
      actually due to indirect responses via the loss of O-antigen. The decreased
      amount of LPS on the DeltarfaH strain cell surface resulted in an attenuated
      stress response, and lower resistance to compounds such as SDS and polymyxin B.
      However, the DeltarfaH strain was significantly more resistant to complement
      mediated killing by normal human serum. Taken together, our results revealed a
      novel role of RfaH acting as a highly specific regulator of O-antigen and OC of
      LPS in Y. enterocolitica O:3. It may be speculated that RfaH might have an in
      vivo role in controlling tissue-specific expression of bacterial surface
      oligo/polysaccharides. 

PMID- 25767109
TI  - Identification of self-growth-inhibiting compounds lauric acid and 7-(Z)
      tetradecenoic acid from Helicobacter pylori.
AB  - Helicobacter pylori growth medium is usually supplemented with horse serum (HS)
      or FCS. However, cyclodextrin derivatives or activated charcoal can replace
      serum. In this study, we purified self-growth-inhibiting (SGI) compounds from H.
      pylori growth medium. The compounds were recovered from porous resin, Diaion HP
      20, which was added to the H. pylori growth medium instead of known supplements.
      These SGI compounds were also identified from 2,6-di-O-methyl-beta-cyclodextrin,
      which was supplemented in a pleuropneumonia-like organisms broth. The growth
      inhibiting compounds were identified as lauric acid (LA) and 7-(Z)-tetradecenoic
      acid [7-(Z)-TDA]. Although several fatty acids had been identified in H. pylori,
      these specific compounds were not previously found in this species. However, we
      confirmed that these fatty acids were universally present in the cultivation
      medium of the H. pylori strains examined in this study. A live/dead assay carried
      out without HS indicated that these compounds were bacteriostatic; however, no
      significant growth-inhibiting effect was observed against other tested bacterial
      species that constituted the indigenous bacterial flora. These findings suggested
      that LA and 7-(Z)-TDA might play important roles in the survival of H. pylori in
      human stomach epithelial cells. 

PMID- 25767110
TI  - Electronic properties of nickel-doped TiO2 anatase.
AB  - Atomistic details of electron transfer in semiconductor materials are
      characterized for TiO2 thin film surfaces doped with nickel. A periodic slab
      model of eight atomic layers exposes the (1 0 0) crystallographic surface and is
      covered with a monolayer of water. The density of states, absorption spectra,
      partial charge densities, molecular dynamics, and non-adiabatic couplings are
      compared between doped and undoped models. Our results show that Ni doping
      improves several electronic properties including lowering the band gap,
      increasing visible light absorption, and shortening the relaxation time of holes
      rather than electrons, which maximizes charge separation. The different
      mechanisms of electron and hole dynamics are discussed. The computed
      characteristics of a doped semiconductor material have practical potential for
      increasing efficiency of a photo-electrochemical cells. 

PMID- 25767111
TI  - Structure-based directed evolution of a monomeric triosephosphate isomerase:
      toward a pentose sugar isomerase.
AB  - Through structure-based and directed evolution approaches, a new catalytic
      activity has been established on the (beta/alpha)8 barrel enzyme triosephosphate
      isomerase (TIM). This work started from ml8bTIM, a monomeric variant of TIM, in
      which the phosphate-binding loop (loop-8) had been shortened. Structure analysis
      suggested an additional point mutation (V233A), converting ml8bTIM into A-TIM. A
      TIM has no detectable TIM activity, but it binds the TIM transition state analog,
      2-phosphoglycollate. In an in vivo selection approach, we aimed at transferring
      the activity of three sugar isomerases (L-arabinose isomerase (L-AI), D-xylose
      isomerase A (D-XI) and D-ribose-5-phosphate isomerase (D-RPI)) onto A-TIM.
      Escherichia coli knockout variants were constructed, lacking E. coli L-AI, D-XI
      and D-RPI activities, respectively. Through a systematic approach, new A-TIM
      variants were obtained only from selection experiments with the L-AI knockout
      strain. Selection for D-RPI activity was impossible because of an impaired strain
      due to the gene knockouts. The selection for D-XI activity was unsuccessful,
      showing the importance of the starting protein for obtaining new biocatalytic
      properties. The L-AI-directed evolution experiments show that A-TIM already has
      residual in vivo L-AI activity. Most of the mutations providing A-TIM with
      enhanced L-AI activity are located in the loops between beta-strands and the
      subsequent alpha-helices.

PMID- 25767112
TI  - Calculated photo-isomerization efficiencies of functionalized azobenzene
      derivatives in solar energy materials: azo-functional organic linkers for porous
      coordinated polymers.
AB  - Recently, we used a local orbital density functional theory code called FIREBALL,
      to study the photoisomerization process in azobenzene derivatives for solar
      energy materials. Azobenzene functional groups undergo photoisomerization upon
      light irradiation or application of heat. Zhou et al (2012 J. Am. Chem. Soc. 134
      99-102) showed that these azobenzenes can then be introduced into metal-organic
      frameworks via an organic linker in order to create a reversible switch for CO2
      adsorption. In this manuscript, we examined how the addition of organic linkers
      (isophthalic acid) changes the relaxation times, isomerization mechanism, and
      quantum yield for both the cis<->trans pathways. We then tuned these properties
      by substituting functional groups, finding an increase in quantum yield as well
      as improved optical properties. 

PMID- 25767113
TI  - Specificity for a CCR5 Inhibitor Is Conferred by a Single Amino Acid Residue:
      ROLE OF ILE198.
AB  - The chemokine receptors CCR5 and CCR2b share 89% amino acid homology. CCR5 is a
      co-receptor for HIV and CCR5 antagonists have been investigated as inhibitors of
      HIV infection. We describe the use of two CCR5 antagonists, Schering-C (SCH-C),
      which is specific for CCR5, and TAK-779, a dual inhibitor of CCR5 and CCR2b, to
      probe the CCR5 inhibitor binding site using CCR5/CCR2b chimeric receptors.
      Compound inhibition in the different chimeras was assessed by inhibition of
      chemokine-induced calcium flux. SCH-C inhibited RANTES (regulated on activation,
      normal T cell expressed and secreted) (CCL5)-mediated calcium flux on CCR5 with
      an IC50 of 22.8 nM but was inactive against monocyte chemoattractant protein-1
      (CCL2)-mediated calcium flux on CCR2b. However, SCH-C inhibited CCL2-induced
      calcium flux against a CCR5/CCR2b chimera consisting of transmembrane domains IV
      VI of CCR5 with an IC50 of 55 nM. A sequence comparison of CCR5 and CCR2b
      identified a divergent amino acid sequence located at the junction of
      transmembrane domain V and second extracellular loop. Transfer of the CCR5
      sequence KNFQTLKIV into CCR2b conferred SCH-C inhibition (IC50 of 122 nM) into
      the predominantly CCR2b chimera. Furthermore, a single substitution, R206I,
      conferred partial but significant inhibition (IC50 of 1023 nM) by SCH-C. These
      results show that a limited amino acid sequence is responsible for SCH-C
      specificity to CCR5, and we propose a model showing the interaction with CCR5
      Ile(198).

PMID- 25767114
TI  - Distinct pathways regulate Syk protein activation downstream of immune tyrosine
      activation motif (ITAM) and hemITAM receptors in platelets.
AB  - Tyrosine kinase pathways are known to play an important role in the activation of
      platelets. In particular, the GPVI and CLEC-2 receptors are known to activate Syk
      upon tyrosine phosphorylation of an immune tyrosine activation motif (ITAM) and
      hemITAM, respectively. However, unlike GPVI, the CLEC-2 receptor contains only
      one tyrosine motif in the intracellular domain. The mechanisms by which this
      receptor activates Syk are not completely understood. In this study, we
      identified a novel signaling mechanism in CLEC-2-mediated Syk activation. CLEC-2
      mediated, but not GPVI-mediated, platelet activation and Syk phosphorylation were
      abolished by inhibition of PI3K, which demonstrates that PI3K regulates Syk
      downstream of CLEC-2. Ibrutinib, a Tec family kinase inhibitor, also completely
      abolished CLEC-2-mediated aggregation and Syk phosphorylation in human and murine
      platelets. Furthermore, embryos lacking both Btk and Tec exhibited cutaneous
      edema associated with blood-filled vessels in a typical lymphatic pattern similar
      to CLEC-2 or Syk-deficient embryos. Thus, our data show, for the first time, that
      PI3K and Tec family kinases play a crucial role in the regulation of platelet
      activation and Syk phosphorylation downstream of the CLEC-2 receptor. 

PMID- 25767115
TI  - Intracellular Na+ regulates epithelial Na+ channel maturation.
AB  - Epithelial Na(+) channel (ENaC) function is regulated by the intracellular Na(+)
      concentration ([Na(+)]i) through a process known as Na(+) feedback inhibition.
      Although this process is known to decrease the expression of proteolytically
      processed active channels on the cell surface, it is unknown how [Na(+)]i alters
      ENaC cleavage. We show here that [Na(+)]i regulates the posttranslational
      processing of ENaC subunits during channel biogenesis. At times when [Na(+)]i is
      low, ENaC subunits develop mature N-glycans and are processed by proteases.
      Conversely, glycan maturation and sensitivity to proteolysis are reduced when
      [Na(+)]i is relatively high. Surface channels with immature N-glycans were not
      processed by endogenous channel activating proteases, nor were they sensitive to
      cleavage by exogenous trypsin. Biotin chase experiments revealed that the
      immature surface channels were not converted into mature cleaved channels
      following a reduction in [Na(+)]i. The hypothesis that [Na(+)]i regulates ENaC
      maturation within the biosynthetic pathways is further supported by the finding
      that Brefeldin A prevented the accumulation of processed surface channels
      following a reduction in [Na(+)]i. Therefore, increased [Na(+)]i interferes with
      ENaC N-glycan maturation and prevents the channel from entering a state that
      allows proteolytic processing. 

PMID- 25767116
TI  - Bicarbonate Modulates Photoreceptor Guanylate Cyclase (ROS-GC) Catalytic
      Activity.
AB  - By generating the second messenger cGMP in retinal rods and cones, ROS-GC plays a
      central role in visual transduction. Guanylate cyclase-activating proteins
      (GCAPs) link cGMP synthesis to the light-induced fall in [Ca(2+)]i to help set
      absolute sensitivity and assure prompt recovery of the response to light. The
      present report discloses a surprising feature of this system: ROS-GC is a sensor
      of bicarbonate. Recombinant ROS-GCs synthesized cGMP from GTP at faster rates in
      the presence of bicarbonate with an ED50 of 27 mM for ROS-GC1 and 39 mM for ROS
      GC2. The effect required neither Ca(2+) nor use of the GCAPs domains; however,
      stimulation of ROS-GC1 was more powerful in the presence of GCAP1 or GCAP2 at low
      [Ca(2+)]. When applied to retinal photoreceptors, bicarbonate enhanced the
      circulating current, decreased sensitivity to flashes, and accelerated flash
      response kinetics. Bicarbonate was effective when applied either to the outer or
      inner segment of red-sensitive cones. In contrast, bicarbonate exerted an effect
      when applied to the inner segment of rods but had little efficacy when applied to
      the outer segment. The findings define a new regulatory mechanism of the ROS-GC
      system that affects visual transduction and is likely to affect the course of
      retinal diseases caused by cGMP toxicity.

PMID- 25767117
TI  - Amyloid precursor protein enhances Nav1.6 sodium channel cell surface expression.
AB  - Amyloid precursor protein (APP) is commonly associated with Alzheimer disease,
      but its physiological function remains unknown. Nav1.6 is a key determinant of
      neuronal excitability in vivo. Because mouse models of gain of function and loss
      of function of APP and Nav1.6 share some similar phenotypes, we hypothesized that
      APP might be a candidate molecule for sodium channel modulation. Here we report
      that APP colocalized and interacted with Nav1.6 in mouse cortical neurons.
      Knocking down APP decreased Nav1.6 sodium channel currents and cell surface
      expression. APP-induced increases in Nav1.6 cell surface expression were Go
      protein-dependent, enhanced by a constitutively active Go protein mutant, and
      blocked by a dominant negative Go protein mutant. APP also regulated JNK activity
      in a Go protein-dependent manner. JNK inhibition attenuated increases in cell
      surface expression of Nav1.6 sodium channels induced by overexpression of APP.
      JNK, in turn, phosphorylated APP. Nav1.6 sodium channel surface expression was
      increased by T668E and decreased by T668A, mutations of APP695 mimicking and
      preventing Thr-668 phosphorylation, respectively. Phosphorylation of APP695 at
      Thr-668 enhanced its interaction with Nav1.6. Therefore, we show that APP
      enhances Nav1.6 sodium channel cell surface expression through a Go-coupled JNK
      pathway. 

PMID- 25767118
TI  - Crystal Structure of the N-Acetylmuramic Acid alpha-1-Phosphate (MurNAc-alpha1-P)
      Uridylyltransferase MurU, a Minimal Sugar Nucleotidyltransferase and Potential
      Drug Target Enzyme in Gram-negative Pathogens.
AB  - The N-acetylmuramic acid alpha-1-phosphate (MurNAc-alpha1-P) uridylyltransferase
      MurU catalyzes the synthesis of uridine diphosphate (UDP)-MurNAc, a crucial
      precursor of the bacterial peptidoglycan cell wall. MurU is part of a recently
      identified cell wall recycling pathway in Gram-negative bacteria that bypasses
      the general de novo biosynthesis of UDP-MurNAc and contributes to high intrinsic
      resistance to the antibiotic fosfomycin, which targets UDP-MurNAc de novo
      biosynthesis. To provide insights into substrate binding and specificity, we
      solved crystal structures of MurU of Pseudomonas putida in native and ligand
      bound states at high resolution. With the help of these structures, critical
      enzyme-substrate interactions were identified that enable tight binding of MurNAc
      alpha1-P to the active site of MurU. The MurU structures define a "minimal
      domain" required for general nucleotidyltransferase activity. They furthermore
      provide a structural basis for the chemical design of inhibitors of MurU that
      could serve as novel drugs in combination therapy against multidrug-resistant
      Gram-negative pathogens. 

PMID- 25767119
TI  - Mutant p53 promotes tumor cell malignancy by both positive and negative
      regulation of the transforming growth factor beta (TGF-beta) pathway.
AB  - Specific p53 mutations abrogate tumor-suppressive functions by gaining new
      abilities to promote tumorigenesis. Inactivation of p53 is known to distort TGF
      beta signaling, which paradoxically displays both tumor-suppressive and pro
      oncogenic functions. The molecular mechanisms of how mutant p53 simultaneously
      antagonizes the tumor-suppressive and synergizes the tumor-promoting function of
      the TGF-beta pathway remain elusive. Here we demonstrate that mutant p53
      differentially regulates subsets of TGF-beta target genes by enhanced binding to
      the MH2 domain in Smad3 upon the integration of ERK signaling, therefore
      disrupting Smad3/Smad4 complex formation. Silencing Smad2, inhibition of ERK, or
      introducing a phosphorylation-defective mutation at Ser-392 in p53 abrogates the
      R175H mutant p53-dependent regulation of these TGF-beta target genes. Our study
      shows a mechanism to reconcile the seemingly contradictory observations that
      mutant p53 can both attenuate and cooperate with the TGF-beta pathway to promote
      cancer cell malignancy in the same cell type. 

PMID- 25767121
TI  - MPs vote for standardised packaging of tobacco products.

PMID- 25767120
TI  - The predominant molecular state of bound enzyme determines the strength and type
      of product inhibition in the hydrolysis of recalcitrant polysaccharides by
      processive enzymes.
AB  - Processive enzymes are major components of the efficient enzyme systems that are
      responsible for the degradation of the recalcitrant polysaccharides cellulose and
      chitin. Despite intensive research, there is no consensus on which step is rate
      limiting for these enzymes. Here, we performed a comparative study of two well
      characterized enzymes, the cellobiohydrolase Cel7A from Hypocrea jecorina and the
      chitinase ChiA from Serratia marcescens. Both enzymes were inhibited by their
      disaccharide product, namely chitobiose for ChiA and cellobiose for Cel7A. The
      products behaved as noncompetitive inhibitors according to studies using the
      (14)C-labeled crystalline polymeric substrates (14)C chitin nanowhiskers and
      (14)C-labeled bacterial microcrystalline cellulose for ChiA and Cel7A,
      respectively. The resulting observed Ki (obs) values were 0.45 +/- 0.08 mm for
      ChiA and 0.17 +/- 0.02 mm for Cel7A. However, in contrast to ChiA, the Ki (obs)
      of Cel7A was an order of magnitude higher than the true Ki value governed by the
      thermodynamic stability of the enzyme-inhibitor complex. Theoretical analysis of
      product inhibition suggested that the inhibition strength and pattern can be
      accounted for by assuming different rate-limiting steps for ChiA and Cel7A.
      Measuring the population of enzymes whose active site was occupied by a polymer
      chain revealed that Cel7A was bound predominantly via its active site.
      Conversely, the active-site-mediated binding of ChiA was slow, and most ChiA
      exhibited a free active site, even when the substrate concentration was
      saturating for the activity. Collectively, our data suggest that complexation
      with the polymer chain is rate-limiting for ChiA, whereas Cel7A is limited by
      dissociation. 

PMID- 25767122
TI  - Discovery and characterization of Ku acetylation in Mycobacterium smegmatis.
AB  - Lysine acetylation is an important post-translational modification and is known
      to regulate many eukaryotic cellular processes. Little, however, is known about
      acetylated proteins in prokaryotes. Here, using immunoblotting, mass spectrometry
      and mutagenesis studies, we investigate the acetylation dynamics of the DNA
      repair protein Ku and its relationship with the deacetylase protein Sir2 and the
      non-homologous end joining (NHEJ) pathway in Mycobacterium smegmatis. We report
      that acetylation of Ku increases with growth, while NHEJ activity decreases,
      providing support for the hypothesis that acetylation of Ku may be involved in
      the DNA damage response in bacteria. Ku has multiple lysine sites. Our results
      indicate that K29 is an important acetylation site and that deficiency of Sir2 or
      mutation of K29 affects the quantity of Ku and its acetylation dynamics. Our
      findings expand knowledge of acetylation targets in prokaryotes and indicate a
      new direction for further research on bacterial DNA repair mechanisms. 

PMID- 25767123
TI  - England launches programme to prevent type 2 diabetes.

PMID- 25767124
TI  - Distress improves after mindfulness training for progressive MS: A pilot
      randomised trial.
AB  - BACKGROUND: Mindfulness-based interventions have been shown to effectively reduce
      anxiety, depression and pain in patients with chronic physical illnesses.
      OBJECTIVES: We assessed the potential effectiveness and cost-effectiveness of a
      specially adapted Skype distant-delivered mindfulness intervention, designed to
      reduce distress for people affected by primary and secondary progressive MS.
      METHODS: Forty participants were randomly assigned to the eight-week intervention
      (n = 19) or a waiting-list control group (n = 21). Participants completed
      standardised questionnaires to measure mood, impact of MS and symptom severity,
      quality of life and service costs at baseline, post-intervention and three-month
      follow-up. RESULTS: Distress scores were lower in the intervention group compared
      with the control group at post-intervention and follow-up (p < 0.05), effect size
      -0.67 post-intervention and -0.97 at follow-up. Mean scores for pain, fatigue,
      anxiety, depression and impact of MS were reduced for the mindfulness group
      compared with control group at post-therapy and follow-up; effect sizes ranged
      from -0.27 to -0.99 post-intervention and -0.29 to -1.12 at follow-up. There were
      no differences in quality-adjusted life years, but an 87.4% probability that the
      intervention saves on service costs and improves outcome. CONCLUSIONS: A
      mindfulness intervention delivered through Skype video conferences appears
      accessible, feasible and potentially effective and cost-effective for people with
      progressive MS.

PMID- 25767125
TI  - The role of epidemiology in MS research: Past successes, current challenges and
      future potential.
AB  - Multiple sclerosis (MS) is a multifaceted condition, with a range of
      environmental, behavioural and genetic factors implicated in its aetiology and
      clinical course. Successes in advancing our appreciation of the roles of Epstein
      Barr virus, vitamin D/UV and the HLA-DRB1 locus; and our greater understanding of
      these and related factors' modes of action in MS and other conditions, can be
      attributed in no small part to the work of generations of epidemiologists. Hardly
      content to rest on our laurels, however, there are yet a range of unsolved
      conundrums in MS, including some changes in epidemiological characteristics (e.g.
      increasing incidence and sex ratio), to say nothing of the unresolved parts
      regarding what underlies MS risk and its clinical course. There is evidence that
      epidemiology will continue to play a crucial role in unravelling the architecture
      of MS causation and clinical course. While classic epidemiological methods are
      ongoing, novel avenues for research include gene-environment interaction studies,
      the world of '-omic' research, and the utilisation of mobile and social media
      tools to both access and track study populations, which means that the
      epidemiological discoveries of the past century may be but a glimpse of our
      understanding in the next few decades. 

PMID- 25767126
TI  - Vitamin D in multiple sclerosis patients: Not the same risk for everybody.

PMID- 25767130
TI  - Temporomandibular disorders.

PMID- 25767129
TI  - Risk of neuropsychiatric adverse events associated with varenicline: systematic
      review and meta-analysis.
AB  - OBJECTIVE: To determine the risk of neuropsychiatric adverse events associated
      with use of varenicline compared with placebo in randomised controlled trials.
      DESIGN: Systematic review and meta-analysis comparing study effects using two
      summary estimates in fixed effects models, risk differences, and Peto odds
      ratios. DATA SOURCES: Medline, Embase, PsycINFO, the Cochrane Central Register of
      Controlled Trials (CENTRAL), and clinicaltrials.gov. ELIGIBILITY CRITERIA FOR
      SELECTING STUDIES: Randomised controlled trials with a placebo comparison group
      that reported on neuropsychiatric adverse events (depression, suicidal ideation,
      suicide attempt, suicide, insomnia, sleep disorders, abnormal dreams, somnolence,
      fatigue, anxiety) and death. Studies that did not involve human participants, did
      not use the maximum recommended dose of varenicline (1 mg twice daily), and were
      cross over trials were excluded. RESULTS: In the 39 randomised controlled trials
      (10,761 participants), there was no evidence of an increased risk of suicide or
      attempted suicide (odds ratio 1.67, 95% confidence interval 0.33 to 8.57),
      suicidal ideation (0.58, 0.28 to 1.20), depression (0.96, 0.75 to 1.22),
      irritability (0.98, 0.81 to 1.17), aggression (0.91, 0.52 to 1.59), or death
      (1.05, 0.47 to 2.38) in the varenicline users compared with placebo users.
      Varenicline was associated with an increased risk of sleep disorders (1.63, 1.29
      to 2.07), insomnia (1.56, 1.36 to 1.78), abnormal dreams (2.38, 2.05 to 2.77),
      and fatigue (1.28, 1.06 to 1.55) but a reduced risk of anxiety (0.75, 0.61 to
      0.93). Similar findings were observed when risk differences were reported. There
      was no evidence for a variation in depression and suicidal ideation by age group,
      sex, ethnicity, smoking status, presence or absence of psychiatric illness, and
      type of study sponsor (that is, pharmaceutical industry or other). CONCLUSIONS:
      This meta-analysis found no evidence of an increased risk of suicide or attempted
      suicide, suicidal ideation, depression, or death with varenicline. These findings
      provide some reassurance for users and prescribers regarding the neuropsychiatric
      safety of varenicline. There was evidence that varenicline was associated with a
      higher risk of sleep problems such as insomnia and abnormal dreams. These side
      effects, however, are already well recognised. SYSTEMATIC REVIEW REGISTRATION:
      PROSPERO 2014:CRD42014009224.

PMID- 25767131
TI  - Association of a lifestyle index with MRI-determined liver fat content in a
      general population study.
AB  - BACKGROUND: In prior studies, lifestyle indices were associated with numerous
      disease end points, but the association with fatty liver disease (FLD), a key
      correlate of cardiometabolic risk, is unknown. The aim was to investigate
      associations between a lifestyle index with liver fat content. METHODS: Liver fat
      was quantified by MRI as liver signal intensity (LSI) in 354 individuals selected
      from a population-based cohort from Germany. Exposure to favourable lifestyle
      factors was quantified using an additive score with each factor modelled as a
      dichotomous trait. Favourable lifestyle factors were defined as waist
      circumference below 102 (men) or 88 cm (women), physical activity >=3.5 h/week,
      never-smoking and a favourable dietary pattern, which was derived to explain
      liver fat variation. In a cross-sectional study, multivariable adjusted linear
      and logistic regression was applied to investigate the association between the
      lifestyle index (range 0-4, exposure) and LSI (modelled as a continuous trait or
      dichotomised as a FLD indicator variable, respectively). RESULTS: Individuals
      with four favourable lifestyle factors (n=9%) had lower LSI values (beta -0.40;
      95% CI -0.61 to -0.19) and a lower OR (0.09; 95% CI 0.03 to 0.30) for FLD
      compared with individuals with zero favourable lifestyle factors (n=10%).
      CONCLUSIONS: A healthy lifestyle pattern was associated with less liver fat.
      Prospective studies are warranted.

PMID- 25767132
TI  - Long working hours and physical activity.
AB  - BACKGROUND: It is widely believed that persons employed in jobs demanding long
      working hours are at greater risk of physical inactivity than other workers,
      primarily because they have less leisure time available to undertake physical
      activity. The aim of this study was to test this hypothesis using prospective
      data obtained from a nationally representative sample of employed persons.
      METHODS: Longitudinal data from the Household, Income and Labour Dynamics in
      Australia Survey (93,367 observations from 17,893 individuals) were used to
      estimate conditional fixed effects logistic regression models of the likelihood
      of moderate or vigorous physical exercise for at least 30 min, at least four
      times a week. RESULTS: No significant associations between long working hours and
      the incidence of healthy levels of physical activity were uncovered once other
      exogenous influences on activity levels were controlled for. The odds of men or
      women who usually work 60 or more hours per week exercising at healthy levels
      were 6% and 11% less, respectively, than those of comparable persons working a
      more standard 35-40 h/week; however, neither estimate was significantly different
      from 0 at 95% CI. CONCLUSIONS: The findings suggest that there is no trade-off
      between long working hours and physical activity in Australia. It is argued that
      these findings are broadly consistent with previous research studies from Anglo
      Saxon countries (where long working hours are pervasive) that employed large
      nationally representative samples.

PMID- 25767133
TI  - Transnational research partnerships: leveraging big data to enhance US health.

PMID- 25767134
TI  - Circadian Variation in Arterial Blood Pressure and Glaucomatous Optic Neuropathy-
      A Systematic Review and Meta-Analysis.
AB  - BACKGROUND: Epidemiological studies have led to equivocal results concerning the
      role of arterial blood pressure as a risk factor for the development of
      glaucomatous damage and progressive visual field loss in glaucoma has been
      attributed to low nighttime blood pressure, especially when oral
      antihypertensives have been combined with beta-blocking eyedrops. In order to
      answer the question whether nocturnal blood pressure or blood pressure dip during
      ambulatory blood pressure monitoring are associated with progressive visual field
      loss we performed a systematic review and meta-analysis of studies in patients
      with primary open-angle glaucoma and normal tension glaucoma. METHODS: After
      searching MEDLINE, the Cochrane Library, and EMBASE, only 5 studies could be
      found reporting information on the method of ambulatory blood pressure
      measurements, separate data for daytime and nighttime blood pressure, definition
      of nocturnal blood pressure dip, and assessment of visual fields over a period of
      at least 2 years. RESULTS: There was no difference in mean systolic or diastolic
      diurnal and nocturnal blood pressure between patients with or without progressive
      visual field loss. The odds ratio for deteriorating visual fields over 2 years
      with nocturnal dips >10% in systolic or diastolic blood pressure was 3.32 (1.84
      6.00) and 2.09 (1.20-3.64), respectively. Data allowing a separate analysis of
      over-dipping were not available. CONCLUSIONS: Nocturnal blood pressure fall is a
      risk factor for progressive visual field loss in glaucoma. However, prospective
      studies are needed to define a tolerable degree of dipping. Antihypertensive
      therapy in glaucomatous patients should be controlled with ambulatory blood
      pressure monitoring.

PMID- 25767135
TI  - Elevation of (Pro)Renin and (Pro)Renin Receptor in Preeclampsia.
AB  - OBJECTIVE: Preeclampsia (preE), a syndrome of hypertension, proteinuria, and
      edema, has many elusive triggers. The renin-angiotensin system has been
      implicated in preE pathogenesis. In this study, we test the hypothesis that
      (pro)renin levels are increased in preE patients and that levels of (pro)renin
      and (pro)renin receptor ((P)RR) are elevated in a rat model of preE. METHODS: We
      recruited 30 preE and 43 normal pregnant consenting patients. We used normally
      pregnant rats (NP, n = 10) and pregnant rats receiving weekly injections of
      desoxycorticosterone acetate and whose drinking water was replaced with 0.9%
      saline (preE, n = 10). Plasma and placental levels of (pro)renin were assayed by
      ELISA. Placental and kidney (P)RR was measured both by immunoblotting and
      immunohistochemistry. RESULTS: The mean plasma (pro)renin of 27.1+/-5.2 in preE
      patients differs from that in patients without preE: 14.8+/-5.2 ng Ang I/ml/hour
      (P < 0.0001). In rats, both plasma (NP: 22.7+/-4.3 and preE: 49.2+/-10.0 ng Ang
      I/ml/hour) and placental (NP: 152+/-24 and preE: 302+/-39 ng/g tissue) levels of
      (pro)renin were higher (P < 0.001) in preE compared to NP rats. (P)RR expression
      was greater (P < 0.05) in placental tissue of preE rats, while kidney (P)RR
      expression was similar. CONCLUSION: Elevated levels of circulating (pro)renin
      have been observed in preE patients and in a rat model of preE. We also found the
      increased expression of placental (P)RR in preE rats.

PMID- 25767136
TI  - Influence of Renal Sympathetic Denervation on Cardiac Extracellular Matrix
      Turnover and Cardiac Fibrosis.
AB  - BACKGROUND: Renal sympathetic denervation (RSD) represents an effective treatment
      option for patients with resistant arterial hypertension (HT). Extracellular
      matrix (ECM) turnover and deposition are essential processes in HT-related
      cardiovascular remodeling, fibrosis, and cardiac hypertrophy and contribute to
      hypertensive heart disease. OBJECTIVES: The primary aim of the present study was
      to examine the effect of RSD on increased collagen turnover as reflected by serum
      levels of amino-terminal pro-peptides (PINP, PIIINP) and a carboxyl-terminal pro
      peptide (PICP), specific biomarkers for cardiac ECM turnover and cardiovascular
      fibrosis. METHODS: A total of 100 consecutive patients (mean age: 65.9+/-10.1
      years) undergoing RSD were included in this study. A therapeutic response was
      defined as an office systolic blood pressure (SBP) reduction of >10mm Hg 6 months
      after RSD. Venous serum samples for measurement of PICP, PINP, and PIIINP were
      collected prior to and 6 months after RSD. RESULTS: A significant reduction in
      the office SBP of 24.3 mm Hg (SBP baseline: 166.9+/-14.3 mm Hg (P < 0.001) was
      documented 6 months after RSD. At this time point, the serum levels of PICP,
      PINP, and PIIINP (P < 0.01) were significantly decreased compared to baseline
      values in patients with an increased collagen turnover, showing significant
      differences comparing BP responders and nonresponders. CONCLUSION: In addition to
      the effective blood pressure reduction in response to RSD, this study
      demonstrates a positive effect of RSD on biomarkers reflecting cardiovascular ECM
      turnover and deposition. These results suggest a beneficial effect of RSD on
      cardiovascular fibrosis, hypertensive heart disease, and end-organ damage in high
      risk patients.

PMID- 25767137
TI  - Orthostatic Changes in Blood Pressure and Mortality in the Elderly: The Pro.V.A
      Study.
AB  - BACKGROUND: An extensive, albeit contrasting literature has suggested a possible
      role for orthostatic hypotension as a risk factor for cardiovascular (CVD) and
      non-CVD mortality, while no data are available for orthostatic hypertension. We
      investigated whether orthostatic changes in blood pressure (BP) were associated
      with any increased risk of all-cause, CVD or non-CVD mortality in a group of
      elderly people. METHODS: Two thousand seven hundred and eighty six community
      dwelling older participants were followed for 4.4 years. Participants were
      grouped according to whether they had a drop <=20 mm Hg in systolic, or <=10 mm
      Hg in diastolic BP (orthostatic hypotension), an increase in mean orthostatic
      systolic BP >=20 (orthostatic hypertension), or normal changes within 3 minutes
      of orthostatism. RESULTS: During follow-up, 640 subjects died, 208 of them for
      CVD-related reasons. Adjusted Cox's regression analysis revealed that, compared
      with normal changes, orthostatic hypertension was associated with higher all
      cause (HR = 1.23; 95% CI: 1.02-1.39) and CVD-related mortality (HR = 1.41; 95%
      CI: 1.08-1.74), while orthostatic hypotension was only associated with a higher
      non-CVD mortality (HR = 1.19; 95% CI: 1.01-1.60). Orthostatic hypertension
      emerged as a predictor of all-cause mortality for: participants over 75 years
      old; participants with a BMI below 25 kg/m2; participants with no CVD or
      disabilities; and those taking less than three medications. Orthostatic
      hypertension also predicted CVD-related mortality in individuals with no
      hypertension, heart failure, coronary artery disease, or atrial fibrillation.
      CONCLUSIONS: Orthostatic hypertension and hypotension both seem to be relevant
      risk factors for mortality in the elderly, orthostatic hypertension correlating
      with all-cause and CVD-related mortality and orthostatic hypotension with non-CVD
      mortality.

PMID- 25767138
TI  - A combination of resistance and endurance training increases leg muscle strength
      in COPD: An evidence-based recommendation based on systematic review with meta
      analyses.
AB  - Resistance training (RT) is thought to be effective in preventing muscle
      depletion, whereas endurance training (ET) is known to improve exercise capacity
      and health-related quality of life (HRQoL) in chronic obstructive pulmonary
      disease (COPD). Our objectives were to assess the efficiency of combining RT with
      ET compared with ET alone. We identified eligible studies through a systematic
      multi-database search. One author checked titles and abstracts for relevance
      using broad inclusion criteria, whilst two independent authors checked the full
      text copies for eligibility. Two authors independently extracted data, and we
      assessed the risk of bias and quality of evidence according to the Grading of
      Recommendations Assessment, Development and Evaluation guidelines. We included 11
      randomized controlled trials (331 participants) and 2 previous systematic
      reviews. The meta-analyses showed equal improvements in HRQoL, walking distance
      and exercise capacity. However, we found moderate quality evidence of a
      significant increase in leg muscle strength favouring a combination of RT and ET
      (standardized mean difference of 0.69 (95% confidence interval: 0.39-0.98). In
      conclusion, we found significantly increased leg muscle strength favouring a
      combination of RT with ET compared with ET alone. Therefore, we recommend that RT
      should be incorporated in rehabilitation of COPD together with ET. 

PMID- 25767139
TI  - Molecular aspects of bovine cystic ovarian disease pathogenesis.
AB  - Cystic ovarian disease (COD) is one of the main causes of reproductive failure in
      cattle and causes severe economic loss to the dairy farm industry because it
      increases both days open in the post partum period and replacement rates due to
      infertility. This disease is the consequence of the failure of a mature follicle
      to ovulate at the time of ovulation in the estrous cycle. This review examines
      the evidence for the role of altered steroid and gonadotropin signaling systems
      and the proliferation/apoptosis balance in the ovary with cystic structures. This
      evidence suggests that changes in the expression of ovarian molecular components
      associated with these cellular mechanisms could play a fundamental role in the
      pathogenesis of COD. The evidence also shows that gonadotropin receptor
      expression in bovine cystic follicles is altered, which suggests that changes in
      the signaling system of gonadotropins could play a fundamental role in the
      pathogenesis of conditions characterized by altered ovulation, such as COD.
      Ovaries from animals with COD exhibit a disrupted steroid receptor pattern with
      modifications in the expression of coregulatory proteins. These changes in the
      pathways of endocrine action would trigger the changes in proliferation and
      apoptosis underlying the aberrant persistence of follicular cysts. Free Spanish
      abstract: A Spanish translation of this abstract is freely available at
      http://www.reproduction-online.org/content/149/6/R251/suppl/DC1.

PMID- 25767140
TI  - Effect of hyperandrogenism on ovarian function.
AB  - The objective of this work was to study the ovarian function when follicular
      development is induced during a hyperandrogenic condition. Female rats were
      injected with either equine chorionic gonadotropin (eCG group) to induce
      folliculogenesis or eCG together with DHEA to induce folliculogenesis in a
      hyperandrogenic condition (eCG+HA group). The control group was injected with
      vehicle. Ovarian mRNA levels of the peroxisome proliferator-activated receptor
      gamma (PPARgamma) co-activator PGC1alpha, the PPARgamma co-repressor NCoR, the
      main enzymes involved in the ovarian steroidogenesis (CYP17, 3beta-hydroxysteroid
      dehydrogenase (3beta-HSD), 17beta-HSD, and CYP19A), and cyclooxygenase 2 (COX2)
      were evaluated only by real-time PCR. COX2 was evaluated by both real-time PCR
      and western blot. Serum steroid hormones and both the oxidative and inflammatory
      statuses were also quantified. We found that eCG-induced folliculogenesis induced
      increased mRNA levels of PGC1alpha and decreased those of NCoR when compared with
      controls. In addition, we found an increase in serum estradiol (E2) levels and
      enhanced mRNA expression of CYP19A. A pro-inflammatory status and a pro-oxidant
      status were also established. When folliculogenesis was induced in a
      hyperandrogenic condition, the mRNA levels of the PPARgamma co-repressor NCoR
      remained higher than in controls and the pro-inflammatory and pro-oxidant
      statuses were enhanced. In addition, the enzymes involved in ovarian
      steroidogenesis were altered leading to the accumulation of testosterone and an
      unfavorable E2/testosterone ratio. These alterations led to abnormal follicular
      development. 

PMID- 25767141
TI  - Human spermatozoa possess an IL4I1 l-amino acid oxidase with a potential role in
      sperm function.
AB  - Reactive oxygen species (ROS) are known to play an important role in the
      regulation of human sperm function. In this study, we demonstrate for the first
      time that human spermatozoa possess interleukin-induced gene 1 (IL4I1), an l
      amino acid oxidase (LAAO) which is capable of generating ROS on exposure to
      aromatic amino acids in the presence of oxygen. The preferred substrates were
      found to be phenylalanine and tryptophan while the enzyme was located in the
      acrosomal region and midpiece of these cells. In contrast to equine and bovine
      spermatozoa, enzyme activity was lost as soon as the spermatozoa became non
      viable. On a cell-to-cell basis human spermatozoa were also shown to generate
      lower levels of hydrogen peroxide than their equine counterparts on exposure to
      phenylalanine. Stimulation of LAAO activity resulted in the induction of several
      hallmarks of capacitation including tyrosine phosphorylation of the sperm
      flagellum and concomitant activation of phospho-SRC expression. In addition,
      stimulation of LAAO resulted in an increase in the levels of acrosomal exocytosis
      in both the presence and absence of progesterone stimulation, via mechanisms that
      could be significantly reversed by the presence of catalase. As is often the case
      with free radical-mediated phenomena, prolonged exposure of human spermatozoa to
      phenylalanine resulted in the stimulation of apoptosis as indicated by
      significant increases in mitochondrial superoxide generation and the activation
      of intracellular caspases. These results confirm the existence of an LAAO in
      human spermatozoa with a potential role in driving the redox regulation of sperm
      capacitation and acrosomal exocytosis. 

PMID- 25767142
TI  - Personal message cards: An evaluation of an alternative method of delivering
      simulated presence therapy.
AB  - Simulated presence therapy is a technique which utilises a familiar recorded
      voice to calm and reassure people with dementia who are agitated or anxious.
      Although simulated presence therapy has shown potential benefits in small-scale
      studies, practical limitations in making and playing the recordings have
      restricted its use. An alternative method of delivering a message from an
      attachment figure is through a personal message card. This was one of seven
      products used within the Bath Memory Technology Library which was made available
      free of charge to people affected by dementia and their carers. This paper
      provides an evaluation of the personal message cards. Although feedback was
      received on only 10 of the 24 cards that were distributed, for nine people there
      was evidence that the cards met the goals that had been set either fully or in
      part, and that people affected by even quite severe levels of dementia could
      benefit from them.

PMID- 25767143
TI  - Developmental thermal plasticity of prey modifies the impact of predation.
AB  - Environmental conditions during embryonic development can influence the mean
      expression of phenotypes as well as phenotypic responses to environmental change
      later in life. The resulting phenotypes may be better matched to their
      environment and more resilient to environmental change, including human-induced
      climate change. However, whether plasticity does improve success in an ecological
      context is unresolved. In a microcosm experiment, we show that developmental
      plasticity in embryos of the frog Limnodynastes peronii is beneficial by
      increasing survivorship of tadpoles in the presence of predators when egg
      incubation (15 or 25 degrees C) and tadpole acclimation temperature in microcosms
      (15 or 25 degrees C) coincided at 15 degrees C. Tadpoles that survived predation
      were smaller, and had faster burst swimming speeds than those kept in no-predator
      control conditions, but only at high (25 degrees C) egg incubation or subsequent
      microcosm temperatures. Metabolic rates were determined by a three-way
      interaction between incubation and microcosm temperatures and predation; maximal
      glycolytic and mitochondrial metabolic capacities (enzyme activities) were lower
      in survivors from predation compared with controls, particularly when eggs were
      incubated at 25 degrees C. We show that thermal conditions experienced during
      early development are ecologically relevant by modulating survivorship from
      predation. Importantly, developmental thermal plasticity also impacts population
      phenotypes indirectly by modifying species interactions and the selection
      pressure imposed by predation.

PMID- 25767144
TI  - Predatory feeding behaviour in Pristionchus nematodes is dependent on phenotypic
      plasticity and induced by serotonin.
AB  - Behavioural innovation and morphological adaptation are intrinsically linked but
      their relationship is often poorly understood. In nematodes, a huge diversity of
      feeding morphologies and behaviours can be observed to meet their distinctive
      dietary and environmental demands. Pristionchus and their relatives show varied
      feeding activities, both consuming bacteria and also predating other nematodes.
      In addition, Pristionchus nematodes display dimorphic mouth structures triggered
      by an irreversible developmental switch, which generates a narrower mouthed form
      with a single tooth and a wider mouthed form with an additional tooth. However,
      little is known about the specific predatory adaptations of these mouth forms or
      the associated mechanisms and behaviours. Through a mechanistic analysis of
      predation behaviours, in particular in the model organism Pristionchus pacificus,
      we reveal multifaceted feeding modes characterised by dynamic rhythmic switching
      and tooth stimulation. This complex feeding mode switch is regulated by the
      neurotransmitter serotonin in a previously uncharacterised role, a process that
      appears conserved across several predatory nematode species. Furthermore, we
      investigated the effects of starvation, prey size and prey preference on P.
      pacificus predatory feeding kinetics, revealing predation to be a fundamental
      component of the P. pacificus feeding repertoire, thus providing an additional
      rich source of nutrition in addition to bacteria. Finally, we found that mouth
      form morphology also has a striking impact on predation, suppressing predatory
      behaviour in the narrow mouthed form. Our results therefore hint at the
      regulatory networks involved in controlling predatory feeding and underscore P.
      pacificus as a model for understanding the evolution of complex behaviours.

PMID- 25767145
TI  - Effects of acceleration on gait measures in three horse gaits.
AB  - Animals switch gaits according to locomotor speed. In terrestrial locomotion,
      gaits have been defined according to footfall patterns or differences in center
      of mass (COM) motion, which characterizes mechanisms that are more general and
      more predictive than footfall patterns. This has generated different variables
      designed primarily to evaluate steady-speed locomotion, which is easier to
      standardize in laboratory conditions. However, in the ecology of an animal,
      steady-state conditions are rare and the ability to accelerate, decelerate and
      turn is essential. Currently, there are no data available that have tested
      whether COM variables can be used in accelerative or decelerative conditions.
      This study used a data set of kinematics and kinetics of horses using three gaits
      (walk, trot, canter) to evaluate the effects of acceleration (both positive and
      negative) on commonly used gait descriptors. The goal was to identify variables
      that distinguish between gaits both at steady state and during
      acceleration/deceleration. These variables will either be unaffected by
      acceleration or affected by it in a predictable way. Congruity, phase shift and
      COM velocity angle did not distinguish between gaits when the dataset included
      trials in unsteady conditions. Work (positive and negative) and energy recovery
      distinguished between gaits and showed a clear relationship with acceleration.
      Hodographs are interesting graphical representations to study COM mechanics, but
      they are descriptive rather than quantitative. Force angle, collision angle and
      collision fraction showed a U-shaped relationship with acceleration and seem
      promising tools for future research in unsteady conditions. 

PMID- 25767146
TI  - Hummingbird flight stability and control in freestream turbulent winds.
AB  - Airflow conditions close to the Earth's surface are often complex, posing
      challenges to flight stability and control for volant taxa. Relatively little is
      known about how well flying animals can contend with complex, adverse air flows,
      or about the flight control mechanisms used by animals to mitigate wind
      disturbances. Several recent studies have examined flight in the unsteady von
      Karman vortex streets that form behind cylinders, generating flow disturbances
      that are predictable in space and time; these structures are relatively rare in
      nature, because they occur only the immediate, downstream vicinity of an object.
      In contrast, freestream turbulence is characterized by rapid, unpredictable flow
      disturbances across a wide range of spatial and temporal scales, and is nearly
      ubiquitous in natural habitats. Hummingbirds are ideal organisms for studying the
      influence of freestream turbulence on flight, as they forage in a variety of
      aerial conditions and are powerful flyers. We filmed ruby-throated hummingbirds
      (Archilochus colubris) maintaining position at a feeder in laminar and strongly
      turbulent (intensity ~15%) airflow environments within a wind tunnel and compared
      their mean kinematics of the head, body, tail and wing, as well as variability in
      these parameters. Hummingbirds exhibited remarkably stable head position and
      orientation in both smooth and turbulent flow while maintaining position at the
      feeder. However, the hummingbird's body was less stable in turbulent flow and
      appeared to be most sensitive to disturbances along the mediolateral axis,
      displaying large lateral accelerations, translations and rolling motions during
      flight. The hummingbirds mitigated these disturbances by increasing mean wing
      stroke amplitude and stroke plane angle, and by varying these parameters
      asymmetrically between the wings and from one stroke to the next. They also
      actively varied the orientation and fan angle of the tail, maintaining a larger
      mean fan angle when flying in turbulent flow; this may improve their passive
      stability, but probably incurs an energetic cost as a result of increased drag.
      Overall, we observed many of the same kinematic changes noted previously for
      hummingbirds flying in a von Karman vortex street, but we also observed kinematic
      changes associated with high force production, similar to those seen during load
      lifting or high-speed flight. These findings suggest that flight may be
      particularly costly in fully mixed, freestream turbulence, which is the flow
      condition that hummingbirds are likely to encounter most frequently in natural
      habitats.

PMID- 25767147
TI  - Single-click beam patterns suggest dynamic changes to the field of view of
      echolocating Atlantic spotted dolphins (Stenella frontalis) in the wild.
AB  - Echolocating animals exercise an extensive control over the spectral and temporal
      properties of their biosonar signals to facilitate perception of their actively
      generated auditory scene when homing in on prey. The intensity and directionality
      of the biosonar beam defines the field of view of echolocating animals by
      affecting the acoustic detection range and angular coverage. However, the spatial
      relationship between an echolocating predator and its prey changes rapidly,
      resulting in different biosonar requirements throughout prey pursuit and capture.
      Here, we measured single-click beam patterns using a parametric fit procedure to
      test whether free-ranging Atlantic spotted dolphins (Stenella frontalis) modify
      their biosonar beam width. We recorded echolocation clicks using a linear array
      of receivers and estimated the beam width of individual clicks using a parametric
      spectral fit, cross-validated with well-established composite beam pattern
      estimates. The dolphins apparently increased the biosonar beam width, to a large
      degree without changing the signal frequency, when they approached the recording
      array. This is comparable to bats that also expand their field of view during
      prey capture, but achieve this by decreasing biosonar frequency. This behaviour
      may serve to decrease the risk that rapid escape movements of prey take them
      outside the biosonar beam of the predator. It is likely that shared sensory
      requirements have resulted in bats and toothed whales expanding their acoustic
      field of view at close range to increase the likelihood of successfully acquiring
      prey using echolocation, representing a case of convergent evolution of
      echolocation behaviour between these two taxa.

PMID- 25767148
TI  - Examining Drinking Patterns and High-Risk Drinking Environments Among College
      Athletes at Different Competition Levels.
AB  - This study examined drinking patterns of three different college student groups:
      (a) intercollegiate athletes, (b) intramural/club athletes, and (c) nonathletes.
      Additionally, we investigated whether a relationship exists between drinking
      setting and risk of increased drinking. We analyzed data on the athletic
      involvement, drinking behaviors, and drinking settings of 16,745 undergraduate
      students. The findings revealed that drinking patterns for intramural/club
      athletes remained relatively consistent at all quantity levels; however,
      intercollegiate athletes consumed alcohol in higher quantities. Further,
      intramural/club athletes drank in almost every drinking setting, whereas
      intercollegiate athletes were more limited. The drinking patterns and settings
      suggest a stronger social motivation for drinking among intramural/club athletes
      than among intercollegiate athletes and point to a need to specify competition
      level when studying college athletes. 

PMID- 25767150
TI  - An in vitro study of thermal necrosis in ultrasonic-assisted drilling of bone.
AB  - In case of human bone fracture, the best way to better and faster knitting is
      when a traumatologist fixes the fractured bone ends by drilling and setting the
      immobilization plates by screws. Heat generation during bone drilling may result
      in thermal injury due to exposure to elevated temperatures, with potentially
      devastating effect on the outcome of orthopedic surgery. A recent and promising
      method for reducing temperature in bone drilling is the use of ultrasonic
      assistance, where high-frequency and low-amplitude vibrations are added in feed
      direction during cutting process. In this research, experimental tests are
      carried out in five cutting speeds and three feed rates. The results demonstrate
      that ultrasonic-assisted drilling offered lower thrust forces and lower process
      temperatures as compared to conventional drilling at 1000 r/min. In addition, it
      is obvious that at 2000 r/min, since the values of temperature rise and thermal
      injury are independent from the feed rate, this method can be applied in the
      orthopedic surgery.

PMID- 25767149
TI  - Variation in viscoelastic properties of bovine articular cartilage below, up to
      and above healthy gait-relevant loading frequencies.
AB  - The aim of this study was to determine the variation in viscoelastic properties
      of femoral head bovine articular cartilage, on-bone, over five orders of
      magnitude of loading frequency. These frequencies ranged from below, up to and
      above healthy gait-relevant frequencies, using<1, 1-5 and 10 Hz, respectively.
      Dynamic mechanical analysis was used to measure storage and loss stiffness. A
      maximum compressive force of 36 N was applied through a chamfered-end, 5.2-mm
      diameter, indenter. This induced a maximum nominal stress of 1.7 MPa. The ratio
      of storage to loss stiffness increased from near parity (2.5) at low frequencies
      to 11.4 at 10 Hz. This was the result of a significant logarithmic increase (p <
      0.05) in storage stiffness with frequency, from 367 N/mm (0.001 Hz) up to 1460
      N/mm (10 Hz). In contrast, the loss stiffness remained approximately constant. In
      conclusion, viscoelastic properties of articular cartilage measured at
      frequencies below those of gait activities are poor predictors of its relevant
      dynamic mechanical behaviour.

PMID- 25767151
TI  - Reverse engineering of complex biological body parts by squared distance enabled
      non-uniform rational B-spline technique and layered manufacturing.
AB  - In tissue engineering, the successful modeling of scaffold for the replacement of
      damaged body parts depends mainly on external geometry and internal architecture
      in order to avoid the adverse effects such as pain and lack of ability to
      transfer the load to the surrounding bone. Due to flexibility in controlling the
      parameters, layered manufacturing processes are widely used for the fabrication
      of bone tissue engineering scaffold with the given computer-aided design model.
      This article presents a squared distance minimization approach for weight
      optimization of non-uniform rational B-spline curve and surface to modify the
      geometry that exactly fits into the defect region automatically and thus to
      fabricate the scaffold specific to subject and site. The study showed that though
      the errors associated in the B-spline curve and surface were minimized by squared
      distance method than point distance method and tangent distance method, the
      errors could be minimized further in the rational B-spline curve and surface as
      the optimal weight could change the shape that desired for the defect site. In
      order to measure the efficacy of the present approach, the results were compared
      with point distance method and tangent distance method in optimizing the non
      rational and rational B-spline curve and surface fitting for the defect site. The
      optimized geometry then allowed to construct the scaffold in fused deposition
      modeling system as an example. The result revealed that the squared distance
      based weight optimization of the rational curve and surface in making the defect
      specific geometry best fits into the defect region than the other methods used. 

PMID- 25767152
TI  - Investigations of micron and submicron wear features of diseased human cartilage
      surfaces.
AB  - Osteoarthritis is a common disease. However, its causes and morphological
      features of diseased cartilage surfaces are not well understood. The purposes of
      this research were (a) to develop quantitative surface characterization
      techniques to study human cartilages at a micron and submicron scale and (b) to
      investigate distinctive changes in the surface morphologies and biomechanical
      properties of the cartilages in different osteoarthritis grades. Diseased
      cartilage samples collected from osteoarthritis patients were prepared for image
      acquisition using two different techniques, that is, laser scanning microscopy at
      a micrometer scale and atomic force microscopy at a nanometer scale. Three
      dimensional, digital images of human cartilages were processed and analyzed
      quantitatively. This study has demonstrated that high-quality three-dimensional
      images of human cartilage surfaces could be obtained in a hydrated condition
      using laser scanning microscopy and atomic force microscopy. Based on the
      numerical data extracted from improved image quality and quantity, it has been
      found that osteoarthritis evolution can be identified by specific surface
      features at the micrometer scale, and these features are amplitude and functional
      property related. At the submicron level, the spatial features of the surfaces
      were revealed to differ between early and advanced osteoarthritis grades. The
      effective indentation moduli of human cartilages effectively revealed the
      cartilage deterioration. The imaging acquisition and numerical analysis methods
      established allow quantitative studies of distinctive changes in cartilage
      surface characteristics and better understanding of the cartilage degradation
      process. 

PMID- 25767153
TI  - Effect of swirling blood flow on vortex formation at post-stenosis.
AB  - Various clinical observations reported that swirling blood flow is a normal
      physiological flow pattern in various vasculatures. The swirling flow has
      beneficial effects on blood circulation through the blood vessels. It enhances
      oxygen transfer and reduces low-density lipoprotein concentration in the blood
      vessel by enhancing cross-plane mixing of the blood. However, the fluid-dynamic
      roles of the swirling flow are not yet fully understood. In this study,
      inhibition of material deposition at the post-stenosis region by the swirling
      flow was observed. To reveal the underlying fluid-dynamic characteristics,
      pathline flow visualization and time-resolved particle image velocimetry
      measurements were conducted. Results showed that the swirling inlet flow
      increased the development of vortices at near wall region of the post-stenosis,
      which can suppress further development of stenosis by enhancing transport and
      mixing of the blood flow. The fluid-dynamic characteristics obtained in this
      study would be useful for improving hemodynamic characteristics of vascular
      grafts and stents in which the stenosis frequently occurred. Moreover, the time
      resolved particle image velocimetry measurement technique and vortex
      identification method employed in this study would be useful for investigating
      the fluid-dynamic effects of the swirling flow on various vascular environments. 

PMID- 25767155
TI  - Drug survival of anti-tumour necrosis factor alpha therapy in
      spondyloarthropathies: results from the Spanish emAR II Study.
AB  - OBJECTIVE: To assess drug survival and the reasons for switching anti-TNF-alpha
      therapy in SpA patients in a Spanish nationwide study. METHODS: A cross-sectional
      study was performed. Sample size was calculated to represent all regions and
      hospitals throughout the country. Demographic data, patient characteristics and
      disease activity parameters were obtained. Drug survival and reasons for
      switching anti-TNF therapy were also recorded. RESULTS: A total of 467 SpA
      patients receiving at least one anti-TNF agent were identified. Among patients
      who received a first, second and third anti-TNF course, 39.4%, 37.4% and 23.1%
      discontinued treatment, respectively. The main reasons for switching anti-TNF
      agents in the first course were lack or loss of efficacy (LOE) and adverse events
      (AEs) in 40% and 30% of switchers, respectively. Similarly, reasons for switching
      during the second anti-TNF course were LOE in 48% and AEs in 28% of switchers. Of
      the 467 SpA patients starting anti-TNF therapy, 28% switched to a second and 8%
      switched to a third therapy. Mean drug survival for the first, second and third
      anti-TNF courses were 84.4 (95% CI 78.4, 90.5), 70.2 (95% CI 61.6, 78.9) and 64.8
      (95% CI 51.1, 78.5) months, respectively (P = 0.315). CONCLUSION: Twenty-eight
      per cent of SpA patients starting anti-TNF therapy switched to a second anti-TNF
      agent. Drug survival did not differ among anti-TNF courses. The main reason for
      switching anti-TNF therapy was LOE. Switchers were more frequently women and had
      higher disease activity parameters at the time of the study than non-switchers.

PMID- 25767157
TI  - Belief in the malleability of groups strengthens the tenuous link between a
      collective apology and intergroup forgiveness.
AB  - Although it is widely assumed that collective apologies for intergroup harms
      facilitate forgiveness, evidence for a strong link between the two remains
      elusive. In four studies we tested the proposition that the apology-forgiveness
      link exists, but only among people who hold an implicit belief that groups can
      change. In Studies 1 and 2, perceived group malleability (measured and
      manipulated, respectively) moderated the responses to an apology by Palestinian
      leadership toward Israelis: Positive responses such as forgiveness increased with
      greater belief in group malleability. In Study 3, university students who
      believed in group malleability were more forgiving of a rival university's
      derogatory comments in the presence (as opposed to the absence) of an apology. In
      Study 4, perceived perpetrator group remorse mediated the moderating effect of
      group malleability on the apology-forgiveness link (assessed in the context of a
      corporate transgression). Implications for collective apologies and movement
      toward reconciliation are discussed. 

PMID- 25767156
TI  - Cytokines in systemic juvenile idiopathic arthritis and haemophagocytic
      lymphohistiocytosis: tipping the balance between interleukin-18 and interferon
      gamma.
AB  - OBJECTIVES: To study the role of IFN-gamma in the pathogenesis of systemic JIA
      (sJIA) and haemophagocytic lymphohistiocytosis (HLH) by searching for an IFN
      gamma profile, and to assess its relationship with other cytokines. METHODS:
      Patients with inactive (n = 10) and active sJIA (n = 10), HLH [n = 5; of which 3
      had sJIA-associated macrophage activation syndrome (MAS)] and healthy controls (n
      = 16) were enrolled in the study. Cytokines and IFN-gamma-induced genes and
      proteins were determined in plasma, in patient peripheral blood mononuclear cells
      (PBMCs) and in lymph node biopsies of one patient during both sJIA and MAS
      episodes. IFN-gamma responses were investigated in healthy donor PBMCs, primary
      fibroblasts and endothelial cells. RESULTS: Plasma IFN-gamma, IL-6 and IL-18 were
      elevated in active sJIA and HLH. Levels of IFN-gamma and IFN-gamma-induced
      proteins (IP-10/CXCL-10, IL-18BP and indoleamine 2,3-dioxygenase) in HLH were
      much higher than levels in active sJIA. Free IL-18 and ratios of IL-18/IFN-gamma
      were higher in active sJIA compared with HLH. HLH PBMCs showed hyporesponsiveness
      to IFN-gamma in vitro when compared with control and sJIA PBMCs. Endothelial
      cells and fibroblasts expressed IFN-gamma-induced proteins in situ in lymph node
      staining of a MAS patient and in vitro upon stimulation with IFN-gamma.
      CONCLUSION: Patients with active sJIA and HLH/MAS show distinct cytokine
      profiles, with highly elevated plasma levels of IFN-gamma and IFN-gamma-induced
      proteins typically found in HLH/MAS. In addition to PBMCs, histiocytes,
      endothelial cells and fibroblasts may contribute to an IFN-gamma profile in
      plasma. Increasing levels of IFN-gamma compared with IL-18 may raise suspicion
      about the development of MAS in sJIA.

PMID- 25767158
TI  - Failure and the aging of society.

PMID- 25767160
TI  - International medical graduates: past, present, and future.

PMID- 25767161
TI  - The PAUSE approach to practising in long-term care.

PMID- 25767164
TI  - Time to rethink EMRs?

PMID- 25767165
TI  - Updated CMPA resource.

PMID- 25767166
TI  - Correction.

PMID- 25767168
TI  - Artificial nutrition and hydration in advanced dementia.

PMID- 25767167
TI  - Frailty: Identifying elderly patients at high risk of poor outcomes.
AB  - OBJECTIVE: To help family physicians better recognize frailty and its
      implications for managing elderly patients. SOURCES OF INFORMATION: PubMed
      MEDLINE was searched from 1990 to 2013. The search was restricted to English
      language articles using the following groups of MeSH headings and key words:
      frail elderly, frail, frailty; aged, geriatrics, geriatric assessment, health
      services for the aged; and primary health care, community health services, and
      family practice. MAIN MESSAGE: Frailty is common, particularly in elderly persons
      with complex chronic conditions such as heart failure and chronic obstructive
      pulmonary disease. Emerging evidence demonstrates the value of frailty as a
      predictor of adverse outcomes in older persons. While there is currently a lack
      of consensus as to how best to assess and diagnose frailty in primary care
      practice, individual markers of frailty such as low gait speed offer a promising
      feasible means of screening for frailty. Identification of frailty in primary
      care might provide an opportunity to delay the progression of frailty through
      proactive interventions such as exercise, and awareness of frailty can guide
      appropriate counseling and anticipatory preventive measures for patients when
      considering medical interventions. Recognition of frailty might also help
      identify and optimize the management of coexisting conditions that might
      contribute to or be affected by frailty. Further research should be directed at
      identifying feasible and effective ways to appropriately assess and manage these
      vulnerable patients at the primary care level. CONCLUSION: Despite its
      importance, little attention has been given to the concept of frailty in family
      medicine. Frailty is easily overlooked because its manifestations can be subtle,
      slowly progressive, and thus dismissed as normal aging; and physician training
      has been focused on specific medical diseases rather than overall vulnerability.
      For primary care physicians, recognition of frailty might help them provide
      appropriate counseling to patients and family members about the risks of medical
      interventions.

PMID- 25767169
TI  - Does ezetimibe modify clinical outcomes?

PMID- 25767170
TI  - Patient with dementia and basal cell carcinoma.

PMID- 25767172
TI  - Painting the landscape of rural medicine.

PMID- 25767171
TI  - Test ordering for preventive health care among family medicine residents.
AB  - OBJECTIVE: To determine which screening tests family medicine residents order as
      part of preventive health care. DESIGN: A cross-sectional survey. SETTING:
      Alberta and Ontario. PARTICIPANTS: First- and second-year family medicine
      residents at the University of Alberta in Edmonton, the University of Calgary in
      Alberta, and McMaster University in Hamilton, Ont, during the 2011 to 2012
      academic year. MAIN OUTCOME MEASURES: Demographic information, Likert scale
      ratings assessing ordering attitudes, and selections from a list of 38 possible
      tests that could be ordered for preventive health care for sample 38-year-old and
      55-year-old female and male patients. Descriptive and comparative statistics were
      calculated. RESULTS: A total of 318 of 482 residents (66%) completed the survey.
      Recommended or appropriate tests were ordered by 82% (for cervical cytology) to
      95% (for fasting glucose measurement) of residents. Across the different sample
      patients, residents ordered an average of 3.3 to 5.7 inappropriate tests per
      patient, with 58% to 92% ordering at least 1 inappropriate test per patient. The
      estimated average excess costs varied from $38.39 for the 38-year-old man to
      $106.46 for the 55-year-old woman. More regular use of a periodic health
      examination screening template did not improve ordering (P = .88). CONCLUSION: In
      general, residents ordered appropriate preventive health tests reasonably well
      but also ordered an average of 3.3 to 5.7 inappropriate tests for each patient.
      Training programs need to provide better education for trainees around
      inappropriate screening and work hard to establish good ordering behaviour in
      preparation for entering practice.

PMID- 25767174
TI  - Crowdsourcing and patient engagement in research.

PMID- 25767175
TI  - We are standing.

PMID- 25767178
TI  - Turbulent times.

PMID- 25767180
TI  - Assessment of structural cardiac abnormalities and diastolic function in women
      with gestational diabetes mellitus.
AB  - BACKGROUND: The main manifestation of hyperglycaemia during pregnancy is
      gestational diabetes mellitus. It can herald diabetes mellitus type 2 and its
      deleterious long-term effects, such as hypertension and cardiovascular disease.
      The aim of this study was to assess diastolic function in women with gestational
      diabetes mellitus, one of the first signs of future cardiovascular disease.
      METHODS: A total of 21 women with gestational diabetes mellitus and 23 healthy
      pregnant women (control group) between 34 and 37 weeks of gestation underwent
      echocardiographic assessment. The diagnosis of gestational diabetes mellitus was
      made in agreement with the American Diabetes Association criteria.
      Echocardiographic images obtained were analysed according to the criteria of the
      American Society of Echocardiography. Data were analysed using Pearson
      correlation coefficient, analysis of variance and Student's t-test. RESULTS:
      Women with gestational diabetes mellitus had higher posterior wall and
      interventricular septum thickness, increased left ventricular mass and left
      ventricular mass index, lower early diastolic annular velocity and early
      diastolic annular velocity/late diastolic annular velocity ratio. There was a
      positive correlation between left ventricular mass index and fasting glucose and
      pregnancy body mass index. CONCLUSION: Patients with gestational diabetes
      mellitus seem to have a different diastolic profile as well as a mildly
      dysfunctional pattern on echocardiogram, which may show a need for greater
      glycaemic control.

PMID- 25767181
TI  - Role of mitochondrial dysfunction in hyperglycaemia-induced coronary
      microvascular dysfunction: Protective role of resveratrol.
AB  - Microvascular complications are now recognized to play a major role in diabetic
      complications, and understanding the mechanisms is critical. Endothelial
      dysfunction occurs early in the course of the development of complications; the
      precise mechanisms remain poorly understood. Mitochondrial dysfunction may occur
      in a diabetic rat heart and may act as a source of the oxidative stress. However,
      the role of endothelial cell-specific mitochondrial dysfunction in diabetic
      vascular complications is poorly studied. Here, we studied the role of diabetes
      induced abnormal endothelial mitochondrial function and the resultant endothelial
      dysfunction. Understanding the role of endothelial mitochondrial dysfunction in
      diabetic vasculature is critical in order to develop new therapies. We
      demonstrate that hyperglycaemia leads to mitochondrial dysfunction in
      microvascular endothelial cells, and that mitochondrial inhibition induces
      endothelial dysfunction. Additionally, we show that resveratrol acts as a
      protective agent; resveratrol-mediated mitochondrial protection may be used to
      prevent long-term diabetic cardiovascular complications. 

PMID- 25767182
TI  - Effect of short-term sensitivity loss in LiF:Mg,Cu,P thermoluminescent dosemeter
      and its implications on personnel dosimetry operations.
AB  - A short-term sensitivity loss in LiF:Mg,Cu,P thermoluminescent dosemeters (TLDs)
      was observed and is described. Its observation occurred during a pre-irradiation
      anneal with a slightly elevated maximum temperature (5-15 degrees C), which
      causes notable under-response (5-10 %) of the subsequent read at the recommended
      time-temperature profile (TTP), which has a peak temperature of 260 degrees C. A
      subsequent irradiation and reading using the recommended TTP showed partial or
      complete recovery of the TLD's sensitivity. To the best of our knowledge, there
      were no publications on possible implications of a one-time 5-15 degrees C
      overheat of LiF:Mg,Cu,P TLDs during anneal. This is not unusual when several
      readers with some variations in their heating cycles are used to calibrate and
      process the same population of dosemeters. A special test to identify if a small
      uncontrolled overheating of a dosemeter element has occurred was developed and
      tested. Two practical implications of the effect of a short-term sensitivity loss
      in LiF:Mg,Cu,P, e.g. inconsistency in results of metrological traceability
      verification and reporting of false neutron doses, are described in detail.
      Simple indicators of a small uncontrolled overheating are provided.

PMID- 25767183
TI  - HydroCoils reduce recurrence rates in recently ruptured medium-sized intracranial
      aneurysms: a subgroup analysis of the HELPS trial.
AB  - BACKGROUND AND PURPOSE: The HydroCoil Endovascular Aneurysm Occlusion and Packing
      Study (HELPS) was a randomized, controlled trial comparing HydroCoils with bare
      platinum coils. The purpose of this study was to perform a subgroup analysis of
      angiographic and clinical outcomes of medium-sized aneurysms in the HELPS trial.
      MATERIALS AND METHODS: Patients with medium-sized aneurysms (5-9.9 mm) were
      selected from the HELPS trial. Outcomes compared between the HydroCoil and bare
      platinum groups included the following: 1) any recurrence, 2) major recurrence,
      3) retreatment, and 4) mRS score of <=2. Subgroup analysis by rupture status was
      performed. Multivariate logistic regression analysis adjusting for aneurysm neck
      size, shape, use of adjunctive device, and rupture status was performed. RESULTS:
      Two hundred eighty-eight patients with medium-sized aneurysms were randomized
      (144 in each group). At 15-18 months posttreatment, the major recurrence rate was
      significantly lower in the HydroCoil group than in controls (18.6% versus 30.8%,
      P = .03, respectively). For patients with recently ruptured aneurysms, the major
      recurrence rate was significantly lower for the HydroCoil group than for controls
      (20.3% versus 47.5%, P = .003), while rates were similar between groups for
      unruptured aneurysms (16.7% versus 14.8%, P = .80). Multivariate analysis of
      patients with recently ruptured aneurysms demonstrated a lower odds of major
      recurrence with HydroCoils (OR = 0.27; 95% CI, 0.12-0.58; P = .0007). No
      difference in retreatment rates or mRS of <=2 was seen between groups.
      CONCLUSIONS: HydroCoils were associated with statistically significant and
      clinically relevant lower rates of major recurrence for recently ruptured, medium
      sized aneurysms in the HELPS trial. Because this was not a prespecified subgroup
      analysis, these results should not alter clinical practice but, rather, provide
      insight into the design of future clinical trials comparing bare platinum with
      second-generation coils.

PMID- 25767184
TI  - Prospective Study of Early MRI Appearances following Flow-Diverting Stent
      Placement for Intracranial Aneurysms.
AB  - BACKGROUND AND PURPOSE: MR imaging findings of aneurysm enlargement, aneurysm
      wall enhancement, perianeurysmal edema, and embolic phenomena following
      deployment of flow-diverting stents may be relevant to those patients who
      subsequently experience procedure-related intracranial hemorrhage. We sought to
      document the routine early postoperative MR imaging findings following flow
      diverting stent insertion. MATERIALS AND METHODS: Patients requiring flow
      diverting stent placement for treatment or retreatment of cerebral aneurysms were
      prospectively included in the study during a 26-month period. Early
      postprocedural MR imaging studies were obtained and compared with preoperative
      imaging. Patient clinical outcome data were also collected. RESULTS: There were
      34 stent-placement procedures during the study period. Aneurysm mural enhancement
      and mild new perianeurysmal edema were present in 50% and 14%, respectively. Any
      DWI lesion was present in 57% of cases. New or possibly new foci of
      susceptibility effect were found ipsilateral to the stent and not associated with
      diffusion restriction in 66% of cases. There were 2 cases (6%) of parenchymal
      hemorrhage and 2 major clinical complications (6%) causing permanent morbidity.
      CONCLUSIONS: Asymptomatic aneurysm mural enhancement is frequently seen following
      flow-diverting stent placement and should not necessarily be interpreted as a
      sign of impending aneurysm rupture. This finding often persists despite complete
      aneurysm occlusion. New small brain parenchymal susceptibility foci following
      stent placement have not previously been reported, to our knowledge, but were
      common in our series.

PMID- 25767185
TI  - Use of Standardized Uptake Value Ratios Decreases Interreader Variability of
      [18F] Florbetapir PET Brain Scan Interpretation.
AB  - BACKGROUND AND PURPOSE: Fluorine-18 florbetapir is a recently developed beta
      amyloid plaque positron-emission tomography imaging agent with high sensitivity,
      specificity, and accuracy in the detection of moderate-to-frequent cerebral
      cortical beta-amyloid plaque. However, the FDA has expressed concerns about the
      consistency of interpretation of [(18)F] florbetapir PET brain scans. We
      hypothesized that incorporating automated cerebral-to-whole-cerebellar
      standardized uptake value ratios into [(18)F] florbetapir PET brain scan
      interpretation would reduce this interreader variability. MATERIALS AND METHODS:
      This randomized, blinded-reader study used previously acquired [(18)F]
      florbetapir scans from 30 anonymized patients who were enrolled in the
      Alzheimer's Disease Neuroimaging Initiative 2. In 4 separate, blinded-reading
      sessions, 5 readers classified 30 cases as positive or negative for significant
      beta-amyloid deposition either qualitatively alone or qualitatively with
      additional adjunct software that determined standardized uptake value ratios. A
      kappa coefficient was used to calculate interreader agreement with and without
      the use of standardized uptake value ratios. RESULTS: There was complete
      interreader agreement on 20/30 cases of [(18)F] florbetapir PET brain scans by
      using qualitative interpretation and on 27/30 scans interpreted with the adjunct
      use of standardized uptake value ratios. The kappa coefficient for the studies
      read with standardized uptake value ratios (0.92) was significantly higher
      compared with the qualitatively read studies (0.69, P = .006). CONCLUSIONS: Use
      of standardized uptake value ratios improves interreader agreement in the
      interpretation of [(18)F] florbetapir images.

PMID- 25767186
TI  - Optimal MRI sequence for identifying occlusion location in acute stroke: which
      value of time-resolved contrast-enhanced MRA?
AB  - BACKGROUND AND PURPOSE: Identifying occlusion location is crucial for determining
      the optimal therapeutic strategy during the acute phase of ischemic stroke. The
      purpose of this study was to assess the diagnostic efficacy of MR imaging,
      including conventional sequences plus time-resolved contrast-enhanced MRA in
      comparison with DSA for identifying arterial occlusion location. MATERIALS AND
      METHODS: Thirty-two patients with 34 occlusion levels referred for thrombectomy
      during acute cerebral stroke events were consecutively included from August 2010
      to December 2012. Before thrombectomy, we performed 3T MR imaging, including
      conventional 3D-TOF and gradient-echo T2 sequences, along with time-resolved
      contrast-enhanced MRA of the extra- and intracranial arteries. The 3D-TOF,
      gradient-echo T2, and time-resolved contrast-enhanced MRA results were
      consensually assessed by 2 neuroradiologists and compared with prethrombectomy
      DSA results in terms of occlusion location. The Wilcoxon test was used for
      statistical analysis to compare MR imaging sequences with DSA, and the kappa
      coefficient was used to determine intermodality agreement. RESULTS: The occlusion
      level on the 3D-TOF and gradient-echo T2 images differed significantly from that
      of DSA (P < .001 and P = .002, respectively), while no significant difference was
      observed between DSA and time-resolved contrast-enhanced MRA (P = .125). kappa
      coefficients for intermodality agreement with DSA (95% CI, percentage agreement)
      were 0.43 (0.3%-0.6; 62%), 0.32 (0.2%-0.5; 56%), and 0.81 (0.6%-1.0; 88%) for 3D
      TOF, gradient-echo T2, and time-resolved contrast-enhanced MRA, respectively.
      CONCLUSIONS: The time-resolved contrast-enhanced MRA sequence proved reliable for
      identifying occlusion location in acute stroke with performance superior to that
      of 3D-TOF and gradient-echo T2 sequences.

PMID- 25767187
TI  - Usefulness of quantitative susceptibility mapping for the diagnosis of Parkinson
      disease.
AB  - BACKGROUND AND PURPOSE: Quantitative susceptibility mapping allows overcoming
      several nonlocal restrictions of susceptibility-weighted and phase imaging and
      enables quantification of magnetic susceptibility. We compared the diagnostic
      accuracy of quantitative susceptibility mapping and R2* (1/T2*) mapping to
      discriminate between patients with Parkinson disease and controls. MATERIALS AND
      METHODS: For 21 patients with Parkinson disease and 21 age- and sex-matched
      controls, 2 radiologists measured the quantitative susceptibility mapping values
      and R2* values in 6 brain structures (the thalamus, putamen, caudate nucleus,
      pallidum, substantia nigra, and red nucleus). RESULTS: The quantitative
      susceptibility mapping values and R2* values of the substantia nigra were
      significantly higher in patients with Parkinson disease (P < .01); measurements
      in other brain regions did not differ significantly between patients and
      controls. For the discrimination of patients with Parkinson disease from
      controls, receiver operating characteristic analysis suggested that the optimal
      cutoff values for the substantia nigra, based on the Youden Index, were >0.210
      for quantitative susceptibility mapping and >28.8 for R2*. The sensitivity,
      specificity, and accuracy of quantitative susceptibility mapping were 90% (19 of
      21), 86% (18 of 21), and 88% (37 of 42), respectively; for R2* mapping, they were
      81% (17 of 21), 52% (11 of 21), and 67% (28 of 42). Pair-wise comparisons showed
      that the areas under the receiver operating characteristic curves were
      significantly larger for quantitative susceptibility mapping than for R2* mapping
      (0.91 versus 0.69, P < .05). CONCLUSIONS: Quantitative susceptibility mapping
      showed higher diagnostic performance than R2* mapping for the discrimination
      between patients with Parkinson disease and controls.

PMID- 25767188
TI  - Reply: To PMID 24948499.

PMID- 25767189
TI  - Head circumference: a key sign in dating abusive head trauma.

PMID- 25767190
TI  - Language and culture modulate online semantic processing.
AB  - Language has been shown to influence non-linguistic cognitive operations such as
      colour perception, object categorization and motion event perception. Here, we
      show that language also modulates higher level processing, such as semantic
      knowledge. Using event-related brain potentials, we show that highly fluent Welsh
      English bilinguals require significantly less processing effort when reading
      sentences in Welsh which contain factually correct information about Wales, than
      when reading sentences containing the same information presented in English.
      Crucially, culturally irrelevant information was processed similarly in both
      Welsh and English. Our findings show that even in highly proficient bilinguals,
      language interacts with factors associated with personal identity, such as
      culture, to modulate online semantic processing. 

PMID- 25767191
TI  - Angiotensin II increases matrix metalloproteinase 2 expression in human aortic
      smooth muscle cells via AT1R and ERK1/2.
AB  - Increased levels of angiotensin II (Ang II) and activated matrix
      metalloproteinase 2 (MMP-2) produced by human aortic smooth muscle cells (human
      ASMCs) have recently been implicated in the pathogenesis of thoracic aortic
      aneurysm (TAA). Additionally, angiotensin II type 1 receptor (AT1R)-mediated
      extracellular signal-regulated kinase (ERK)1/2 activation contributes to TAA
      development in Marfan Syndrome. However, there is scant data regarding the
      relationship between Ang II and MMP-2 expression in human ASMCs. Therefore, we
      investigated the effect of Ang II on MMP-2 expression in human ASMCs and used
      Western blotting to identify the Ang II receptors and intracellular signaling
      pathways involved. Reverse transcription polymerase chain reaction (RT-PCR) and
      immunofluorescence data demonstrated that Ang II receptors were expressed on
      human ASMCs. Additionally, Ang II increased the expression of Ang II type 2
      receptor (AT2R) but not AT1R at both the transcriptional and translational
      levels. Furthermore, Western blotting showed that Ang II increased MMP-2
      expression in human ASMCs in a dose- and time-dependent manner. This response was
      completely inhibited by the AT1R inhibitor candesartan but not by the AT2R
      blocker PD123319. In addition, Ang II-induced upregulation of MMP-2 was mediated
      by the activation of ERK1/2, whereas p38 mitogen-activated protein kinase (p38
      MAPK) and c-Jun N-terminal kinase (JNK) had no effect on this process. In
      conclusion, these results indicate that Ang II can increase the expression of MMP
      2 via AT1 receptor and ERK1/2 signaling pathways in human ASMCs and suggest that
      antagonists of AT1R and ERK1/2 may be useful for treating TAAs. 

PMID- 25767193
TI  - Schizophrenia: Stigma and the Impact of Literature.

PMID- 25767192
TI  - Fibrin patch-based insulin-like growth factor-1 gene-modified stem cell
      transplantation repairs ischemic myocardium.
AB  - Bone marrow mesenchymal stem cells (BMSCs), tissue-engineered cardiac patch, and
      therapeutic gene have all been proposed as promising therapy strategies for
      cardiac repair after myocardial infarction. In our study, BMSCs were modified
      with insulin-like growth factor-1 (IGF-1) gene, loaded into a fibrin patch, and
      then transplanted into a porcine model of ischemia/reperfusion (I/R) myocardium
      injury. The results demonstrated that IGF-1 gene overexpression could promote
      proliferation of endothelial cells and cardiomyocyte-like differentiation of
      BMSCs in vitro. Four weeks after transplantation of fibrin patch loaded with gene
      modified BMSCs, IGF-1 overexpression could successfully promote angiogenesis,
      inhibit remodeling, increase grafted cell survival and reduce apoptosis. In
      conclusion, the integrated strategy, which combined fibrin patch with IGF-1 gene
      modified BMSCs, could promote the histological cardiac repair for a clinically
      relevant porcine model of I/R myocardium injury.

PMID- 25767194
TI  - Compulsory community and involuntary outpatient treatment for people with severe
      mental disorders.
AB  - There is controversy as to whether compulsory community treatment (CCT) for
      people with severe mental illness (SMI) reduces health service use or improves
      clinical outcome and social functioning. To examine the effectiveness of CCT for
      people with SMI. We searched the Cochrane Schizophrenia Group's Trials Register
      and Science Citation Index (2003, 2008, 2012, and 2013). We obtained all
      references of identified studies and contacted authors where necessary. All
      relevant randomized controlled clinical trials (RCTs) of CCT compared with
      standard care for people with SMI (mainly schizophrenia and schizophrenia-like
      disorders, bipolar disorder, or depression with psychotic features). Standard
      care could be voluntary treatment in the community or another preexisting form of
      compulsory community treatment such as supervised discharge. We found 3 trials
      with a total of 752 people. Two trials compared a form of CCT called 'Outpatient
      Commitment' (OPC) versus standard voluntary care, whereas the third compared
      Community Treatment Orders with intermittent supervised discharge. CCT was no
      more likely to result in better service use, social functioning, mental state, or
      quality of life compared with either standard voluntary or supervised care.
      However, people receiving CCT were less likely to be victims of crime than those
      on voluntary care. Further research is indicated into the effects of different
      types of CCT as these results are based on 3 relatively small trials. 

PMID- 25767195
TI  - Biomechanical Analysis of an Arthroscopic Brostrom Ankle Ligament Repair and a
      Suture Anchor-Augmented Repair.
AB  - BACKGROUND: Secondary surgical repair of ankle ligaments is often indicated in
      cases of chronic lateral ankle instability. Recently, arthroscopic Brostrom
      techniques have been described, but biomechanical information is limited. The
      purpose of the present study was to analyze the biomechanical properties of an
      arthroscopic Brostrom repair and augmented repair with a proximally placed suture
      anchor. It was hypothesized that the arthroscopic Brostrom repairs would compare
      favorably to open techniques and that augmentation would increase the mean repair
      strength at time zero. METHODS: Twenty (10 matched pairs) fresh-frozen foot and
      ankle cadaveric specimens were obtained. After sectioning of the lateral ankle
      ligaments, an arthroscopic Brostrom procedure was performed on each ankle using
      two 3.0-mm suture anchors with #0 braided polyethylene/polyester multifilament
      sutures. One specimen from each pair was augmented with a 2.9-mm suture anchor
      placed 3 cm proximal to the inferior tip of the lateral malleolus. Repairs were
      isolated and positioned in 20 degrees of inversion and 10 degrees of
      plantarflexion and loaded to failure using a dynamic tensile testing machine.
      Maximum load (N), stiffness (N/mm), and displacement at maximum load (mm) were
      recorded. RESULTS: There were no significant differences between standard
      arthroscopic repairs and the augmented repairs for mean maximum load and
      stiffness (154.4 +/- 60.3 N, 9.8 +/- 2.6 N/mm vs 194.2 +/- 157.7 N, 10.5 +/- 4.7
      N/mm, P = .222, P = .685). CONCLUSIONS: Repair augmentation did not confer a
      significantly higher mean strength or stiffness at time zero. CLINICAL RELEVANCE:
      Mean strength and stiffness for the arthroscopic Brostrom repair compared
      favorably with previous similarly tested open repair and reconstruction methods,
      validating the clinical feasibility of an arthroscopic repair. However,
      augmentation with an additional proximal suture anchor did not significantly
      strengthen the repair.

PMID- 25767196
TI  - Obesity Is Associated With Increased Complications After Operative Management of
      End-Stage Ankle Arthritis.
AB  - BACKGROUND: Total ankle arthroplasty (TAA) and ankle arthrodesis (AA) are two
      operative options for the management of end-stage ankle arthritis that has failed
      conservative interventions. Obesity is associated with a greater incidence of
      musculoskeletal disease, particularly osteoarthritis of the weight-bearing
      joints, including the ankle. The objective of the present study was to use a
      national database to examine the association between obesity and postoperative
      complications after TAA and AA. METHODS: The PearlDiver database was queried for
      patients undergoing AA and TAA using International Classification of Diseases,
      9th Revision (ICD-9) procedure codes. Patients were divided into obese (body mass
      index >=30 kg/m(2)) and nonobese (body mass index <30 kg/m(2)) cohorts using ICD
      9 codes for body mass index and obesity. Complications within 90 days
      postoperatively were assessed using ICD-9 and Current Procedural Terminology
      (CPT) codes. RESULTS: 23,029 patients were identified from 2005 to 2011,
      including 5361 with TAA and 17,668 with AA. Obese TAA patients had a
      significantly increased risk of 90-day major, minor, local, systemic, venous
      thromboembolic, infectious, and medical complications compared with nonobese
      patients. The incidence of revision TAA was also significantly higher in obese
      patients compared with nonobese patients. Findings were similar for AA, as all
      types of complications were significantly higher in obese patients compared with
      nonobese patients. CONCLUSION: Obesity was associated with significantly
      increased rates of all complications after both TAA and AA. The cause of this
      association was likely multifactorial, including increased rates of medical
      comorbidities, intraoperative factors, and larger soft tissue envelopes. LEVEL OF
      EVIDENCE: Level III, comparative series.

PMID- 25767197
TI  - Oklahoma Retailers' Perspectives on Mutual Benefit Exchange to Limit Point-of
      Sale Tobacco Advertisements.
AB  - Businesses changing their practices in ways that support tobacco control efforts
      recently have gained interest, as demonstrated by CVS Health's voluntary policy
      to end tobacco sales. Point-of-sale (POS) advertisements are associated with
      youth smoking initiation, increased tobacco consumption, and reduced quit
      attempts among smokers. There is interest in encouraging retailers to limit
      tobacco POS advertisements voluntarily. This qualitative exploratory study
      describes Oklahoma tobacco retailers' perspectives on a mutual benefit exchange
      approach, and preferred message and messenger qualities that would entice them to
      take voluntary action to limit tobacco POS advertisements. This study found that
      mutual benefit exchange could be a viable option along with education and law as
      strategies to create behavior change among tobacco retailers. Many retailers
      stated that they would be willing to remove noncontractual POS advertisements for
      a 6-month commitment period when presented with mutual exchange benefit, tailored
      message, and appropriate messenger. Mutual benefit exchange, as a behavior change
      strategy to encourage voluntary removal of POS tobacco advertisements, was
      acceptable to retailers, could enhance local tobacco control in states with
      preemption, and may contribute to setting the foundation for broader legislative
      efforts. 

PMID- 25767198
TI  - Ingenious strategies of microbial pathogens.

PMID- 25767199
TI  - Membrane traffic: endocytotic dynamics and regulation.

PMID- 25767200
TI  - Control of cellular homeostasis: organelles take the pilot's seat.

PMID- 25767201
TI  - Cell motion and mechanobiology.

PMID- 25767202
TI  - Lipids, GTPases, and their regulators in membrane dynamics: an intracellular
      menage a trois.

PMID- 25767203
TI  - Protein sorting to intracellular compartments.

PMID- 25767204
TI  - Quantitative Description of a Protein Fitness Landscape Based on Molecular
      Features.
AB  - Understanding the driving forces behind protein evolution requires the ability to
      correlate the molecular impact of mutations with organismal fitness. To address
      this issue, we employ here metallo-beta-lactamases as a model system, which are
      Zn(II) dependent enzymes that mediate antibiotic resistance. We present a study
      of all the possible evolutionary pathways leading to a metallo-beta-lactamase
      variant optimized by directed evolution. By studying the activity, stability and
      Zn(II) binding capabilities of all mutants in the preferred evolutionary
      pathways, we show that this local fitness landscape is strongly conditioned by
      epistatic interactions arising from the pleiotropic effect of mutations in the
      different molecular features of the enzyme. Activity and stability assays in
      purified enzymes do not provide explanatory power. Instead, measurement of these
      molecular features in an environment resembling the native one provides an
      accurate description of the observed antibiotic resistance profile. We report
      that optimization of Zn(II) binding abilities of metallo-beta-lactamases during
      evolution is more critical than stabilization of the protein to enhance fitness.
      A global analysis of these parameters allows us to connect genotype with fitness
      based on quantitative biochemical and biophysical parameters. 

PMID- 25767206
TI  - Corrigendum: The unforeseen costs of extraordinary experience.
AB  - Cooney, G., Gilbert, D. T., & Wilson, T. D. (2014). The unforeseen costs of
      extraordinary experience. Psychological Science, 25, 2259-2265. (Original DOI:
      10.1177/0956797614551372). 

PMID- 25767207
TI  - Corrigendum: Life paths and accomplishments of mathematically precocious males
      and females four decades later.
AB  - Lubinski, D., Benbow, C. P., & Kell, H. J. (2014). Life paths and accomplishments
      of mathematically precocious males and females four decades later. Psychological
      Science, 25, 2217-2232. (Original DOI: 10.1177/0956797614551371). 

PMID- 25767205
TI  - Ancient Origin and Recent Innovations of RNA Polymerase IV and V.
AB  - Small RNA-mediated chromatin modification is a conserved feature of eukaryotes.
      In flowering plants, the short interfering (si)RNAs that direct transcriptional
      silencing are abundant and subfunctionalization has led to specialized machinery
      responsible for synthesis and action of these small RNAs. In particular, plants
      possess polymerase (Pol) IV and Pol V, multi-subunit homologs of the canonical
      DNA-dependent RNA Pol II, as well as specialized members of the RNA-dependent RNA
      Polymerase (RDR), Dicer-like (DCL), and Argonaute (AGO) families. Together these
      enzymes are required for production and activity of Pol IV-dependent (p4-)siRNAs,
      which trigger RNA-directed DNA methylation (RdDM) at homologous sequences. p4
      siRNAs accumulate highly in developing endosperm, a specialized tissue found only
      in flowering plants, and are rare in nonflowering plants, suggesting that the
      evolution of flowers might coincide with the emergence of specialized RdDM
      machinery. Through comprehensive identification of RdDM genes from species
      representing the breadth of the land plant phylogeny, we describe the ancient
      origin of Pol IV and Pol V, suggesting that a nearly complete and functional RdDM
      pathway could have existed in the earliest land plants. We also uncover
      innovations in these enzymes that are coincident with the emergence of seed
      plants and flowering plants, and recent duplications that might indicate
      additional subfunctionalization. Phylogenetic analysis reveals rapid evolution of
      Pol IV and Pol V subunits relative to their Pol II counterparts and suggests that
      duplicates were retained and subfunctionalized through Escape from Adaptive
      Conflict. Evolution within the carboxy-terminal domain of the Pol V largest
      subunit is particularly striking, where illegitimate recombination facilitated
      extreme sequence divergence. 

PMID- 25767208
TI  - Bilingualism modulates infants' selective attention to the mouth of a talking
      face.
AB  - Infants growing up in bilingual environments succeed at learning two languages.
      What adaptive processes enable them to master the more complex nature of
      bilingual input? One possibility is that bilingual infants take greater advantage
      of the redundancy of the audiovisual speech that they usually experience during
      social interactions. Thus, we investigated whether bilingual infants' need to
      keep languages apart increases their attention to the mouth as a source of
      redundant and reliable speech cues. We measured selective attention to talking
      faces in 4-, 8-, and 12-month-old Catalan and Spanish monolingual and bilingual
      infants. Monolinguals looked more at the eyes than the mouth at 4 months and more
      at the mouth than the eyes at 8 months in response to both native and nonnative
      speech, but they looked more at the mouth than the eyes at 12 months only in
      response to nonnative speech. In contrast, bilinguals looked equally at the eyes
      and mouth at 4 months, more at the mouth than the eyes at 8 months, and more at
      the mouth than the eyes at 12 months, and these patterns of responses were found
      for both native and nonnative speech at all ages. Thus, to support their dual
      language acquisition processes, bilingual infants exploit the greater perceptual
      salience of redundant audiovisual speech cues at an earlier age and for a longer
      time than monolingual infants. 

PMID- 25767209
TI  - Sadness shifts to anxiety over time and distance from the national tragedy in
      Newtown, Connecticut.
AB  - How do increasing temporal and spatial distance affect the emotions people feel
      and express in response to tragic events? Standard views suggest that emotional
      intensity should decrease but are silent on changes in emotional quality. Using a
      large Twitter data set, we identified temporal and spatial patterns in use of
      emotional and cognitive words in tweets about the Sandy Hook Elementary School
      shooting. Although use of sadness words decreased with time and spatial distance,
      use of anxiety words showed the opposite pattern and was associated with
      concurrent increases in language reflecting causal thinking. In a follow-up
      experiment, we found that thinking about abstract causes (as opposed to concrete
      details) of this event similarly evoked decreased sadness but increased anxiety,
      which was associated with perceptions that a similar event might occur in the
      future. These data challenge current theories of emotional reactivity and
      identify time, space, and abstract causal thinking as factors that elicit
      categorical shifts in emotional responses to tragedy. 

PMID- 25767212
TI  - Residents' awareness and attitudes about an ongoing community-based genome cohort
      study in Nagahama, Japan.
AB  - This study's objective was to examine residents' attitudes toward and factors
      associated with an ongoing, real genome cohort study based on a community in
      Japan. After the genome cohort study's launch in 2007, in November and December
      2009, a self-administered questionnaire survey was conducted with 2500 randomly
      sampled residents aged 30-74 years, living in Nagahama, Japan. Responses were
      received from 1363 people (response rate = 54.5%), of whom 187 respondents had
      already participated in the study. Although the local government and researchers
      disseminated information through leaflets and citizen-information papers to every
      household, sent notices by personalized letter, and held symposia and other
      meetings, 65.7% of males and 47.2% of females first became aware of the study
      when they received our questionnaire. Among all respondents, 81.2% of those who
      knew that the genome cohort study had begun and 68.6% of those who did not know
      had a positive attitude toward the study. Their attitudes were significantly
      associated with high health consciousness and the desire for an extensive health
      check-up. Although for males there were no particular negative aspects of the
      genome study, for females, positive aspects were associated with participating in
      community activities and desiring an extensive health check-up. Although
      promoting a community-based genome cohort study requires huge effort, it is
      essential to popularize it. Actions are vital both for monitoring public
      awareness and attitudes at a community level and for keeping communication
      channels open.

PMID- 25767210
TI  - Homologous Mutation to Human BRAF V600E Is Common in Naturally Occurring Canine
      Bladder Cancer--Evidence for a Relevant Model System and Urine-Based Diagnostic
      Test.
AB  - Targeted cancer therapies offer great clinical promise, but treatment resistance
      is common, and basic research aimed at overcoming this challenge is limited by
      reduced genomic and biologic complexity in artificially induced rodent tumors
      compared with their human counterparts. Animal models that more faithfully
      recapitulate genotype-specific human pathology could improve the predictive value
      of these investigations. Here, a newly identified animal model for oncogenic BRAF
      driven cancers is described. With 20,000 new cases in the United States each
      year, canine invasive transitional cell carcinoma of the bladder (InvTCC) is a
      common, naturally occurring malignancy that shares significant histologic,
      biologic, and clinical phenotypes with human muscle invasive bladder cancer. In
      order to identify somatic drivers of canine InvTCC, the complete transcriptome
      for multiple tumors was determined by RNAseq. All tumors harbored a somatic
      mutation that is homologous to the human BRAF(V600E) mutation, and an identical
      mutation was present in 87% of 62 additional canine InvTCC tumors. The mutation
      was also detectable in the urine sediments of all dogs tested with mutation
      positive tumors. Functional experiments suggest that, like human tumors, canine
      activating BRAF mutations potently stimulate the MAPK pathway. Cell lines with
      the mutation have elevated levels of phosphorylated MEK, compared with a line
      with wild-type BRAF. This effect can be diminished through application of the
      BRAF(V600E) inhibitor vemurafenib. These findings set the stage for canine InvTCC
      as a powerful system to evaluate BRAF-targeted therapies, as well as therapies
      designed to overcome resistance, which could enhance treatment of both human and
      canine cancers IMPLICATIONS: This study demonstrates the activating BRAF mutation
      (V600E), which is found in multiple human cancers, is a driver of canine InvTCC,
      and highlights a urine-based test for quick diagnosis.

PMID- 25767211
TI  - Targeting nodal in conjunction with dacarbazine induces synergistic anticancer
      effects in metastatic melanoma.
AB  - Metastatic melanoma is a highly aggressive skin cancer with a poor prognosis.
      Despite a complete response in fewer than 5% of patients, the chemotherapeutic
      agent dacarbazine (DTIC) remains the reference drug after almost 40 years. More
      recently, FDA-approved drugs have shown promise but patient outcome remains
      modest, predominantly due to drug resistance. As such, combinatorial targeting
      has received increased attention, and will advance with the identification of new
      molecular targets. One attractive target for improving melanoma therapy is the
      growth factor Nodal, whose normal expression is largely restricted to embryonic
      development, but is reactivated in metastatic melanoma. In this study, we sought
      to determine how Nodal-positive human melanoma cells respond to DTIC treatment
      and to ascertain whether targeting Nodal in combination with DTIC would be more
      effective than monotherapy. A single treatment with DTIC inhibited cell growth
      but did not induce apoptosis. Rather than reducing Nodal expression, DTIC
      increased the size of the Nodal-positive subpopulation, an observation coincident
      with increased cellular invasion. Importantly, clinical tissue specimens from
      patients with melanomas refractory to DTIC therapy stained positive for Nodal
      expression, both in pre- and post-DTIC tumors, underscoring the value of
      targeting Nodal. In vitro, anti-Nodal antibodies alone had some adverse effects
      on proliferation and apoptosis, but combining DTIC treatment with anti-Nodal
      antibodies decreased cell growth and increased apoptosis synergistically, at
      concentrations incapable of producing meaningful effects as monotherapy.
      IMPLICATIONS: Targeting Nodal in combination with DTIC therapy holds promise for
      the treatment of metastatic melanoma.

PMID- 25767213
TI  - Characterization of diastolic dysfunction heart failure following an acute
      hospitalization for heart failure in an urban, underserved population.
AB  - OBJECTIVES: The aim of this retrospective study was to describe demographic and
      clinical characteristics of patients with diastolic dysfunction heart failure
      (DHF) in a safety-net institution. METHODS: Descriptive statistics were used to
      summarize characteristics for adults with DHF hospitalized for acute
      decompensated heart failure (ADHF) between 1 January 2009 and 30 June 2010.
      RESULTS: Of 483 patients with an ADHF-related admission, only 83 (17.2%) had pure
      DHF. Mean age was 59.6 +/- 13.1 years old, with nearly equal proportions of male
      and female patients. Hypertension (89.2%), coronary artery disease (74.7%), and
      diabetes (63.9%) comorbidities were most common. Diuretics (91.6%), angiotensin
      converting enzyme inhibitors or angiotensin receptor blockers (69.9%), and beta
      blockers (60.3%) were most frequently prescribed on discharge. CONCLUSION: In our
      population, DHF is more prevalent in younger patients of any ethnicity,
      especially Hispanic/Latino and black ethnicities, compared with nationwide
      estimates. Our patients with DHF had higher ejection fractions and were
      prescribed higher rates of traditional heart failure medications.

PMID- 25767215
TI  - Potential Impact and Cost-effectiveness of Self-Testing for HIV in Low-Income
      Countries.

PMID- 25767214
TI  - Assessment of the Potential Impact and Cost-effectiveness of Self-Testing for HIV
      in Low-Income Countries.
AB  - BACKGROUND: Studies have demonstrated that self-testing for human
      immunodeficiency virus (HIV) is highly acceptable among individuals and could
      allow cost savings, compared with provider-delivered HIV testing and counseling
      (PHTC), although the longer-term population-level effects are uncertain. We
      evaluated the cost-effectiveness of introducing self-testing in 2015 over a 20
      year time frame in a country such as Zimbabwe. METHODS: The HIV synthesis model
      was used. Two scenarios were considered. In the reference scenario, self-testing
      is not available, and the rate of first-time and repeat PHTC is assumed to
      increase from 2015 onward, in line with past trends. In the intervention
      scenario, self-testing is introduced at a unit cost of $3. RESULTS: We predict
      that the introduction of self-testing would lead to modest savings in healthcare
      costs of $75 million, while averting around 7000 disability-adjusted life-years
      over 20 years. Findings were robust to most variations in assumptions; however,
      higher cost of self-testing, lower linkage to care for people whose diagnosis is
      a consequence of a positive self-test result, and lower threshold for
      antiretroviral therapy eligibility criteria could lead to situations in which
      self-testing is not cost-effective. CONCLUSIONS: This analysis suggests that
      introducing self-testing offers some health benefits and may well save costs.

PMID- 25767216
TI  - Macrolides Promote CCL2-Mediated Macrophage Recruitment and Clearance of
      Nasopharyngeal Pneumococcal Colonization in Mice.
AB  - BACKGROUND: Streptococcus pneumoniae (pneumococcus) colonizes mucosal surfaces of
      the upper respiratory tract (URT), resulting in invasive disease. Macrolides are
      known for their immunomodulatory effects. We investigated the potency of
      macrolides to reduce pneumococcal colonization by activating host innate
      immunity. METHODS: The kinetics of colonization, cellular response, and
      inflammatory cytokine levels in the URT were assessed after nasal inoculation of
      pneumococci. EM900 (a novel 12-membered nonantibiotic macrolide with an
      immunomodulatory effect) was orally administered throughout the experiment.
      Survival was evaluated for 10 days. Macrolide-mediated CCL2 production from
      peritoneal macrophages was determined by enzyme-linked immuosorbent assay. The
      cell-signaling pathway was analyzed by means of Western blotting and gene
      silencing assays. RESULTS: Streptococcus pneumoniae was significantly reduced
      from EM900-treated mice 14 days after pneumococcal inoculation. Macrophage
      recruitment and Ccl2 messenger RNA expression were promoted. CCL2 production from
      peritoneal macrophages was significantly induced by macrolides and was dependent
      on NF-kappaB phosphorylation through the myeloid differentiation primary-response
      gene 88- or TIR domain-containing adapter-inducing interferon-beta-mediated
      pathway. Mortality of mice with invasive pneumococcal disease was improved by
      pretreatment with EM900. CONCLUSIONS: Macrolides may inhibit invasive
      pneumococcal infections by accelerating the clearance of pneumococcal
      nasopharyngeal colonization via promotion of macrophage-mediated innate immunity.

PMID- 25767217
TI  - Whole-Genome Sequence for Methicillin-Resistant Staphylococcus aureus Strain ATCC
      BAA-1680.
AB  - We report here the whole-genome sequence of the USA300 strain of methicillin
      resistant Staphylococcus aureus (MRSA), designated ATCC BAA-1680, and commonly
      referred to as community-associated MRSA (CA-MRSA). This clinical MRSA isolate is
      commercially available from the American Type Culture Collection (ATCC) and is
      widely utilized as a control strain for research applications and clinical
      diagnosis. The isolate was propagated in ATCC medium 18, tryptic soy agar, and
      has been utilized as a model S. aureus strain in several studies, including MRSA
      genetic analysis after irradiation with 470-nm blue light. 

PMID- 25767218
TI  - Complete coding genome sequence of putative novel bluetongue virus serotype 27.
AB  - We announce the complete coding genome sequence of a novel bluetongue virus (BTV)
      serotype (BTV-n = putative BTV-27) detected in goats in Corsica, France, in 2014.
      Sequence analysis confirmed the closest relationship between sequences of the
      novel BTV serotype and BTV-25 and BTV-26, recently discovered in Switzerland and
      Kuwait, respectively. 

PMID- 25767219
TI  - Whole-Genome Sequence of "Candidatus Rickettsia asemboensis" Strain NMRCii,
      Isolated from Fleas of Western Kenya.
AB  - Herein we present the draft genome sequence and annotation of "Candidatus
      Rickettsia asemboensis" strain NMRCii. "Ca. Rickettsia asemboensis" is
      phylogenetically related to but distinct from the flea-borne spotted fever
      pathogen Rickettsia felis. "Ca. Rickettsia asemboensis" was initially identified
      in and subsequently isolated from Ctenocephalides cat and dog fleas from Kenya. 

PMID- 25767220
TI  - Draft Genome Sequence of Halomonas sp. KHS3, a Polyaromatic Hydrocarbon
      Chemotactic Strain.
AB  - The draft genome sequence of Halomonas sp. KHS3, isolated from seawater from Mar
      del Plata harbor, is reported. This strain is able to grow using aromatic
      compounds as a carbon source and shows strong chemotactic response toward these
      substrates. Genes involved in motility, chemotaxis, and degradation of aromatic
      hydrocarbons were identified. 

PMID- 25767221
TI  - Genome Sequence of Acinetobacter baumannii Strain A1, an Early Example of
      Antibiotic-Resistant Global Clone 1.
AB  - Acinetobacter baumannii isolate A1 was recovered in the United Kingdom in 1982
      and belongs to global clone 1 (GC1). Here, we present its complete 3.91-Mbp
      genome sequence, generated via a combination of short-read sequencing (Illumina),
      long-read sequencing (PacBio), and manual finishing. 

PMID- 25767222
TI  - Genomes of Geoalkalibacter ferrihydriticus Z-0531T and Geoalkalibacter
      subterraneus Red1T, Two Haloalkaliphilic Metal-Reducing Deltaproteobacteria.
AB  - We sequenced and annotated genomes of two haloalkaliphilic Deltaproteobacteria,
      Geoalkalibacter ferrihydriticus Z-0531(T) (DSM 17813) and Geoalkalibacter
      subterraneus Red1(T) (DSM 23483). During assembly, we discovered that the DSMZ
      stock culture of G. subterraneus was contaminated. We reisolated G. subterraneus
      in axenic culture and redeposited it in DSMZ and JCM. 

PMID- 25767223
TI  - Complete Genome Sequence of a Metronidazole-Resistant Helicobacter pylori Strain.
AB  - We report here the complete genome sequence of a metronidazole-resistant
      Helicobacter pylori strain (MET(r)). The MET(r) strain was obtained under
      exposure of H. pylori 26695 on agar plates with low metronidazole concentrations.
      The genome data provide insight into the genomic changes of H. pylori under
      selection by metronidazole in vitro. 

PMID- 25767224
TI  - Complete Genome Sequence of Paenibacillus polymyxa Strain Sb3-1, a Soilborne
      Bacterium with Antagonistic Activity toward Plant Pathogens.
AB  - The genome of Paenibacillus polymyxa Sb3-1, a strain that shows antagonistic
      activities against pathogenic fungi and bacteria, consists of one 5.6-Mb circular
      chromosome and two plasmids of 223 kb and 8 kb. The genome reveals several genes
      that potentially contribute to its antagonistic and plant growth promotion
      activity. 

PMID- 25767225
TI  - Draft Genome Sequence of the Filamentous Fungus Penicillium paxilli (ATCC 26601).
AB  - Penicillium paxilli ATCC 26601 is an asexual filamentous fungal species known for
      its production of the mycotoxin paxilline. We present here the 35-Mb draft genome
      sequence for this organism. 

PMID- 25767226
TI  - Draft Genome Sequences of Clostridium tyrobutyricum Strains FAM22552 and
      FAM22553, Isolated from Swiss Semihard Red-Smear Cheese.
AB  - Clostridium tyrobutyricum is the main microorganism responsible for late blowing
      defect in cheeses. Here, we present the draft genome sequences of two C.
      tyrobutyricum strains isolated from a Swiss semihard red-smear cheese. The two
      draft genomes comprise 3.05 and 3.08 Mbp and contain 3,030 and 3,089 putative
      coding sequences, respectively. 

PMID- 25767227
TI  - Draft Genome Sequence of Nocardia seriolae Strain N-2927 (NBRC 110360), Isolated
      as the Causal Agent of Nocardiosis of Yellowtail (Seriola quinqueradiata) in
      Kochi Prefecture, Japan.
AB  - We report the draft genome sequence of Nocardia seriolae strain N-2927 (NBRC
      110360), isolated from cultured yellowtail Seriola quinqueradiata. RAST
      annotation of the genome revealed 117 genes involved in the virulence, disease,
      and defense subsystem. Eleven of these genes were predicted as antibiotic
      resistance genes. 

PMID- 25767228
TI  - Two Complete and One Draft Genome Sequence of Nonproteolytic Clostridium
      botulinum Type E Strains NCTC 8266, NCTC 8550, and NCTC 11219.
AB  - Group II (gII) nonproteolytic Clostridium botulinum strains are a major cause of
      foodborne botulism outbreaks. Here, we report two complete genome sequences of
      gII type E strains NCTC 8266 and NCTC 8550 and one draft genome sequence of type
      E NCTC 11219. 

PMID- 25767229
TI  - Complete Genome Sequence of Bacillus subtilis subsp. subtilis Strain 3NA.
AB  - Bacillus subtilis 3NA reaches high cell densities during fed-batch fermentation
      and is an interesting target for further optimization as a production strain.
      Here, we announce the full genome of B. subtilis 3NA. The presence of specific
      Bacillus subtilis 168 and W23 genetic features suggests that 3NA is a hybrid of
      these strains. 

PMID- 25767230
TI  - Complete genome sequence of emerging porcine circovirus types 2a and 2b from
      India.
AB  - We report here the first characterized complete genome sequence of porcine
      circovirus types 2a and 2b from northeastern states of India. These isolates may
      serve as a potential reference for the Indian strains of porcine circovirus types
      2a and 2b. 

PMID- 25767231
TI  - Draft Genome Sequences of Two Strains of Serratia spp. from the Midgut of the
      Malaria Mosquito Anopheles gambiae.
AB  - Here, we report the annotated draft genome sequences of two strains of Serratia
      spp., Ag1 and Ag2, isolated from the midgut of two different strains of Anopheles
      gambiae. The genomes of these two strains are almost identical. 

PMID- 25767233
TI  - Genome Sequences of Mannheimia haemolytica Serotype A2 Isolates D171 and D35,
      Recovered from Bovine Pneumonia.
AB  - Here, we report two genomes, one complete and one draft, from isolates of
      serotype A2 Mannheimia haemolytica recovered from pneumonic bovine lung. 

PMID- 25767232
TI  - High-Quality Draft Genome Sequence of Desulfovibrio carbinoliphilus FW-101-2B, an
      Organic Acid-Oxidizing Sulfate-Reducing Bacterium Isolated from Uranium(VI)
      Contaminated Groundwater.
AB  - Desulfovibrio carbinoliphilus subsp. oakridgensis FW-101-2B is an anaerobic,
      organic acid/alcohol-oxidizing, sulfate-reducing delta-proteobacterium. FW-101-2B
      was isolated from contaminated groundwater at The Field Research Center at Oak
      Ridge National Lab after in situ stimulation for heavy metal-reducing conditions.
      The genome will help elucidate the metabolic potential of sulfate-reducing
      bacteria during uranium reduction. 

PMID- 25767234
TI  - Draft Genome Sequence of Lactobacillus plantarum Lp90 Isolated from Wine.
AB  - Here, we describe the draft genome sequence and annotation of Lactobacillus
      plantarum strain Lp90, the first sequenced genome of a L. plantarum strain
      isolated from wine. This strain has a noticeable ropy phenotype and showed
      potential probiotic properties. The genome consists of 3,324,076 bp (33 contigs)
      and contains 3,155 protein coding genes, 34 pseudogenes, and 84 RNA genes. 

PMID- 25767235
TI  - Complete Genome Sequence of Bacillus amyloliquefaciens Strain BH072, Isolated
      from Honey.
AB  - The genome of Bacillus amyloliquefaciens strain BH072, isolated from a honey
      sample and showing strong antimicrobial activity against plant pathogens, is 4.07
      Mb and harbors 3,785 coding sequences (CDS). Several gene clusters for
      nonribosomal synthesis of antimicrobial peptides and a complete gene cluster for
      biosynthesis of mersacidin were detected. 

PMID- 25767236
TI  - Draft Genome Sequences of Vibrio renopiscarius Strains CECT 8603T and CECT 8604,
      Two Marine Gammaproteobacteria Isolated from Cultured Gilthead Sea Bream (Sparus
      aurata).
AB  - Vibrio renopiscarius DCR 1-4-2(T) (CECT 8603(T)) and DCR 1-4-12 (CECT 8604) were
      isolated from healthy gilthead sea bream (Sparus aurata) from Mediterranean fish
      farms (Castellon, Spain). Their draft genome sequences (30 and 44 contigs,
      respectively) have 4.3 Mbp and a G+C content of 45.2 mol% and contain almost
      3,700 protein-encoding genes. 

PMID- 25767237
TI  - Genome Sequence Analysis Reveals Evidence of Quorum-Sensing Genes Present in
      Aeromonas hydrophila Strain M062, Isolated from Freshwater.
AB  - Aeromonas hydrophila has emerged worldwide as a human pathogen. Here, we report
      the draft whole-genome sequence of a freshwater isolate from Malaysia, A.
      hydrophila strain M062, and its N-acylhomoserine lactone genes are also reported
      here. 

PMID- 25767238
TI  - Genome Sequence of an Efficient Indole-Degrading Bacterium, Cupriavidus sp.
      Strain IDO, with Potential Polyhydroxyalkanoate Production Applications.
AB  - Cupriavidus sp. strain IDO has been shown to efficiently transform indole, and
      the genus of Cupriavidus has been described as a promising cell factory for
      polyhydroxyalkanoate synthesis from low-cost wastes. Here, we report the draft
      genome sequence of strain IDO, which may provide useful genetic information on
      indole metabolism and polyhydroxyalkanoate production. 

PMID- 25767239
TI  - Draft genome sequences of gammaproteobacterial methanotrophs isolated from lake
      washington sediment.
AB  - The genomes of Methylosarcina lacus LW14(T) (=ATCC BAA-1047(T) = JCM 13284(T)),
      Methylobacter sp. strain 21/22, Methylobacter sp. strain 31/32, Methylomonas sp.
      strain LW13, Methylomonas sp. strain MK1, and Methylomonas sp. strain 11b were
      sequenced and are reported here. All the strains are obligately methanotrophic
      bacteria isolated from the sediment of Lake Washington. 

PMID- 25767240
TI  - Complete genomic sequence for an avian group G rotavirus from South Africa.
AB  - We report the first complete sequence for an avian group G rotavirus (RVG) genome
      from Africa, which is the third publically available RVG genome. These RVG
      genomes are highly diverse, especially in their VP4, VP7, NSP4, and NSP3
      segments, indicating that RVG diversity is comparable to that of rotavirus A. 

PMID- 25767241
TI  - Genome Sequence of Corynebacterium ulcerans Strain FRC11.
AB  - Here, we present the genome sequence of Corynebacterium ulcerans strain FRC11.
      The genome includes one circular chromosome of 2,442,826 bp (53.35% G+C content),
      and 2,210 genes were predicted, 2,146 of which are putative protein-coding genes,
      with 12 rRNAs and 51 tRNAs; 1 pseudogene was also identified. 

PMID- 25767242
TI  - Genome Sequence of the Urethral Catheter Isolate Pseudomonas aeruginosa MH19.
AB  - Pseudomonas aeruginosa is a frequent agent of complicated catheter-associated
      urinary tract infections (CAUTIs). Here, we present the improved 7.1-Mb draft
      genome sequence of P. aeruginosa MH19, which was isolated from a patient with an
      acute hospital-acquired CAUTI. It includes unique genes not represented in other
      P. aeruginosa genomes. 

PMID- 25767243
TI  - Genome sequences of equid herpesviruses 2 and 5.
AB  - We resequenced the genome of equid herpesvirus 2 (EHV2) strain 86/67 and
      sequenced the genomes of EHV2 strain G9/92 and equid herpesvirus 5 (EHV5) strain
      2-141/67. The most prominent genetic differences are the dissimilar locations of
      the interleukin-10 (IL-10)-like genes and the presence of an OX-2-like gene in
      EHV5 only. 

PMID- 25767244
TI  - Draft Genome Sequence of Bordetella avium Nh1210, an Outbreak Strain of Lockjaw
      Syndrome.
AB  - Bordetella avium is a highly contagious bacterium that infects the upper
      respiratory tract of birds. B. avium Nh1210 is an outbreak strain of lockjaw
      syndrome in juvenile cockatiel chicks (Nymphicus hollandicus). Here, we report
      the draft genome sequence of strain Nh1210. 

PMID- 25767245
TI  - Complete Genome Sequence of Mycoplasma flocculare Strain Ms42T (ATCC 27399T).
AB  - Mycoplasma flocculare is a commensal or low-virulence pathogen of swine. The
      complete 778,866-bp genome sequence of M. flocculare strain Ms42(T) has been
      determined, enabling further comparison to genomes of the closely related
      pathogen Mycoplasma hyopneumoniae. The absence of the p97 and glpD genes may
      contribute to the attenuated virulence of M. flocculare. 

PMID- 25767246
TI  - Complete Genome Sequences of Influenza A/H1N1 Strains Isolated from Patients
      during the 2013-2014 Epidemic Season in Finland.
AB  - Here, we report 40 complete genome sequences of influenza A/H1N1 strains isolated
      from 33 nonhospitalized and 7 hospitalized patients during the 2013-2014 epidemic
      season in Finland. An analysis of the aligned sequences revealed no oseltamivir
      resistant genotypes. As a whole, the recent viruses have drifted from the
      prototype A/California/7/2009 virus by ca. 1.3%. 

PMID- 25767247
TI  - Draft Genome Sequences of Five Spore-Forming Food Isolates of Bacillus pumilus.
AB  - Here, we report the draft genome sequences of five food isolates of Bacillus
      pumilus, a spore-forming Gram-positive bacterium. 

PMID- 25767248
TI  - De novo assembly and annotation of the Asian tiger mosquito (Aedes albopictus)
      repeatome with dnaPipeTE from raw genomic reads and comparative analysis with the
      yellow fever mosquito (Aedes aegypti).
AB  - Repetitive DNA, including transposable elements (TEs), is found throughout
      eukaryotic genomes. Annotating and assembling the "repeatome" during genome-wide
      analysis often poses a challenge. To address this problem, we present dnaPipeTE-a
      new bioinformatics pipeline that uses a sample of raw genomic reads. It produces
      precise estimates of repeated DNA content and TE consensus sequences, as well as
      the relative ages of TE families. We shows that dnaPipeTE performs well using
      very low coverage sequencing in different genomes, losing accuracy only with old
      TE families. We applied this pipeline to the genome of the Asian tiger mosquito
      Aedes albopictus, an invasive species of human health interest, for which the
      genome size is estimated to be over 1 Gbp. Using dnaPipeTE, we showed that this
      species harbors a large (50% of the genome) and potentially active repeatome with
      an overall TE class and order composition similar to that of Aedes aegypti, the
      yellow fever mosquito. However, intraorder dynamics show clear distinctions
      between the two species, with differences at the TE family level. Our pipeline's
      ability to manage the repeatome annotation problem will make it helpful for new
      or ongoing assembly projects, and our results will benefit future genomic studies
      of A. albopictus. 

PMID- 25767254
TI  - A proposed nationwide reporting system to satisfy the ethical obligation to
      prevent drug diversion-related transmission of hepatitis C in healthcare
      facilities.
AB  - In 2012, dozens of patients of Exeter Hospital in New Hampshire contracted new
      hepatitis C infections that were tracked back to a cardiac technician who
      ultimately confessed to drug diversion. A multistate epidemiological
      investigation of hepatitis C cases occurring in multiple hospitals revealed that
      the technician had been fired from prior institutions due to similar drug
      diversion activity, about which Exeter Hospital had not been notified. In this
      article, we highlight the institutional ethical issues raised by this outbreak,
      and propose a national centralized reporting system to support institutional
      fulfillment of the ethical obligation to protect the health of patients by
      preventing such nosocomial outbreaks. 

PMID- 25767249
TI  - Detecting endogenous retrovirus-driven tissue-specific gene transcription.
AB  - Transposable elements (TEs) comprise approximately half of the human genome, and
      several independent lines of investigation have demonstrated their role in
      rewiring gene expression during development, evolution, and oncogenesis. The
      identification of their regulatory effects has largely been idiosyncratic, by
      linking activity with isolated genes. Their distribution throughout the genome
      raises critical questions-do these elements contribute to broad tissue- and
      lineage-specific regulation? If so, in what manner, as enhancers, promoters,
      RNAs? Here, we devise a novel approach to systematically dissect the genome-wide
      consequences of TE insertion on gene expression, and test the hypothesis that
      classes of endogenous retrovirus long terminal repeats (LTRs) exert tissue
      specific regulation of adjacent genes. Using correlation of expression patterns
      across 18 tissue types, we reveal the tissue-specific uncoupling of gene
      expression due to 62 different LTR classes. These patterns are specific to the
      retroviral insertion, as the same genes in species without the LTRs do not
      exhibit the same effect. Although the LTRs can be transcribed themselves, the
      most highly transcribed TEs do not have the largest effects on adjacent
      regulation of coding genes, suggesting they function predominantly as enhancers.
      Moreover, the tissue-specific patterns of gene expression that are detected by
      our method arise from a limited number of genes, rather than as a general
      consequence of LTR integration. These findings identify basic principles of co
      opting LTRs for genome evolution, and support the utility of our method for the
      analysis of TE, or other specific gene sets, in relation to the rest of the
      genome. 

PMID- 25767255
TI  - Stopping possible sexual transmission of filoviruses.

PMID- 25767257
TI  - Thalassemia major is a major risk factor for pediatric melioidosis in Kota
      Kinabalu, Sabah, Malaysia.
AB  - BACKGROUND: Melioidosis is an important cause of community-acquired infection in
      Southeast Asia and northern Australia. Studies from endemic countries have
      demonstrated differences in the epidemiology and clinical features among children
      diagnosed with melioidosis. This suggests that local data are needed to determine
      the risk factors and outcome in specific areas. METHODS: This was a retrospective
      study of all children admitted to Likas Women's and Children Hospital, Kota
      Kinabalu, Sabah, Malaysia, with a blood or clinical sample positive for
      Burkholderia pseudomallei from 2001 to 2012. RESULTS: Of 28 children with
      confirmed melioidosis, 27 records were reviewed including 11 (41%) children with
      thalassemia major. Twenty of the children had bacteremia, and 16 (59%) had a
      fatal outcome. Six children had chronic disease, and none died. Empiric use of
      antibiotics not specific for B. pseudomallei was associated with increased risk
      of death (P < .001). The annual incidence of melioidosis in children with
      thalassemia major from 2001 to 2010 was 140 per 100 000/year vs 0.33 per 100
      000/year for other children (P < .001). After institution of iron chelation
      therapy in 2010, no child with thalassemia major was diagnosed with melioidosis
      in 2011 or 2012. CONCLUSIONS: Pediatric melioidosis in Sabah is associated with a
      high proportion of bacteremia and death. Thalassemia major was a major risk
      factor for melioidosis among children from 2001 to 2010, but infections decreased
      markedly from 2011 to 2012 after universal availability of iron chelation
      therapy. Inappropriate empiric therapy was associated with an increased risk of
      death.

PMID- 25767258
TI  - Ten-year Survival by Race/Ethnicity and Sex Among Treated, HIV-infected Adults in
      the United States.
AB  - BACKGROUND: Ensuring equal access to antiretroviral therapy (henceforth therapy)
      should alleviate disparities in health outcomes among persons infected with human
      immunodeficiency virus (HIV). However, evidence supporting the persistence of
      disparities in survival following therapy initiation is mixed. METHODS: Patients
      initiating therapy in eight academic medical centers in the Centers for AIDS
      Research Network of Integrated Clinical Systems between 1 January 1998 and 30
      December 2011. Patients (n = 10 017) were followed from therapy initiation until
      death from any cause, administrative censoring at 10 years after therapy
      initiation or the end of follow-up on 31 December 2011. The 10-year risk of all
      cause mortality was calculated from standardized Kaplan-Meier survival curves.
      RESULTS: Patients were followed for a median of 4.7 years (interquartile range:
      2.2, 8.2). During 51 121 person-years of follow-up, 1224 of the 10 017 patients
      died. The overall 10-year mortality risk was 20.2% (95% confidence interval [CI],
      19.2%, 21.3%). Black men and women experienced standardized 10-year all-cause
      mortality risks that were 7.2% (95% CI, 4.3%, 10.1%) and 7.9% (95% CI, 3.9%,
      12.0%) larger (absolute difference) than white men. White women, Hispanic men,
      and Hispanic women all had lower 10-year mortality than white men. CONCLUSIONS:
      These data serve as a call to action to identify modifiable mechanisms leading to
      these observed mortality disparities among HIV-infected black patients. Effective
      interventions are needed to ensure that the goal of the National HIV/AIDS
      Strategy to overcome health disparities becomes a reality.

PMID- 25767256
TI  - Comparison of the metabolic effects of ritonavir-boosted darunavir or atazanavir
      versus raltegravir, and the impact of ritonavir plasma exposure: ACTG 5257.
AB  - BACKGROUND: Metabolic effects following combination antiretroviral therapy (cART)
      vary by regimen type. Changes in metabolic effects were assessed following cART
      in the AIDS Clinical Trials Group (ACTG) A5257 study, and correlated with plasma
      ritonavir trough concentrations (C24). METHODS: Treatment-naive adult subjects
      were randomized to ritonavir-boosted atazanavir or darunavir, or raltegravir
      based cART. Changes in lipids and other metabolic outcomes over time were
      estimated. Differences between arms were estimated with 97.5% confidence
      intervals and compared using pairwise Student t tests. Associations between
      ritonavir C24 and lipid changes at week 48 were evaluated via linear regression.
      RESULTS: Analyses included 1797 subjects with baseline fasting data. Baseline
      lipid profiles and metabolic syndrome rates (approximately 21%) were similar
      across arms. Comparable increases occurred in total cholesterol, triglycerides,
      and low-density lipoprotein cholesterol with the boosted protease inhibitors
      (PIs); each PI had greater increases relative to raltegravir (all P <= .001 at
      week 96). Metabolic syndrome incident rates by week 96 (approximately 22%) were
      not different across arms. Ritonavir C24 was not different by arm (P = .89)
      (median, 69 ng/mL and 74 ng/mL in the atazanavir and darunavir arms,
      respectively) and were not associated with changes in lipid measures (all P >
      .1). CONCLUSIONS: Raltegravir produced the most favorable lipid profile.
      Metabolic syndrome rates were high at baseline and increased to the same degree
      in all arms. Ritonavir C24 was not different in the PI arms and had no
      relationship with the modest but comparable increases in lipids observed with
      either atazanavir or darunavir. The long-term clinical significance of the lipid
      changes noted with the PIs relative to raltegravir deserves further evaluation.
      CLINICAL TRIALS REGISTRATION: NCT 00811954.

PMID- 25767259
TI  - Selective sodium-dependent glucose transporter 1 inhibitors block glucose
      absorption and impair glucose-dependent insulinotropic peptide release.
AB  - GSK-1614235 and KGA-2727 are potent, selective inhibitors of the SGLT1 sodium
      dependent glucose transporter. Nonclinical (KGA-2727) and clinical (GSK-1614235)
      trials assessed translation of SGLT1 inhibitor effects from rats to normal human
      physiology. In rats, KGA-2727 (0.1 mg/kg) or vehicle was given before oral
      administration of 3-O-methyl-alpha-d-glucopyranose (3-O-methylglucose, 3-OMG)
      containing 3-[3H]OMG tracer. Tracer absorption and distribution were assessed
      from plasma, urine, and fecal samples. SGLT1 inhibition reduced urine 3-OMG
      recovery and increased fecal excretion. SGLT1 inhibitor effects on plasma
      glucose, insulin, gastric inhibitory peptide (GIP), and glucagon-like peptide-1
      (GLP-1) concentrations were also measured during a standard meal. Incremental
      glucose, insulin, and GIP concentrations were decreased, indicating
      downregulation of beta-cell and K cell secretion. Minimal effects were observed
      in the secretion of the L cell product, GLP-1. With the use of a three-way,
      crossover design, 12 healthy human subjects received placebo or 20 mg GSK-1614235
      immediately before or after a meal. Five minutes into the meal, 3-OMG was
      ingested. Postmeal dosing had little impact, yet premeal dosing delayed and
      reduced 3-OMG absorption, with an AUC0-10 of 231+/-31 vs. 446+/-31 MUg.h(-1).ml(
      1), for placebo. Recovery of tracer in urine was 1.2+/-0.7 g for premeal dosing
      and 2.2+/-0.1 g for placebo. Incremental concentrations of insulin, C-peptide,
      and GIP were reduced for 2 h with premeal GSK-1614235. Total GLP-1 concentrations
      were significantly increased, and a trend for increased peptide YY (PYY) was
      noted. SGLT1 inhibitors block intestinal glucose absorption and reduce GIP
      secretion in rats and humans, suggesting SGLT1 glucose transport is critical for
      GIP release. Conversely, GLP-1 and PYY secretion are enhanced by SGLT1 inhibition
      in humans.

PMID- 25767260
TI  - Zinc deficiency mediates alcohol-induced apoptotic cell death in the liver of
      rats through activating ER and mitochondrial cell death pathways.
AB  - Hepatic zinc deficiency has been well documented in alcoholic patients, but the
      mechanisms by which zinc deficiency mediates cell death have not been well
      defined. The objectives of this study were to determine whether alcohol perturbs
      subcellular zinc homeostasis and how organelle zinc depletion may link with cell
      death pathways. Wistar rats were pair-fed with the Lieber-DeCarli control or
      ethanol diet for 5 mo. Chronic alcohol exposure significantly reduced zinc level
      in isolated hepatic endoplasmic reticulum (ER) and mitochondria. Among the
      detected zinc transporters, ER Zrt/Irt-like protein (ZIP)13 and mitochondrial
      ZIP8, which transport zinc from ER and mitochondria to cytosol, were
      significantly increased. Mitochondrial zinc transporter (ZnT) 4, which transports
      zinc from cytosol to mitochondria, was also increased. ER phosphorylated
      eukaryotic initiation factor 2alpha, activating transcription factor 4, and C/EBP
      homologous protein were significantly upregulated, and mitochondrial cytochrome c
      release and Bax insertion were detected in association with caspase-3 activation
      and apoptotic cell death. To define the role of zinc deficiency in ER and
      mitochondrial stress, H4IIEC3 cells were treated with 3 MUM N,N,N',N'-tetrakis (2
      pyridylmethyl) ethylenediamine for 6 h with or without supplementation with zinc
      or N-acetylcysteine (NAC). The results demonstrated that zinc deprivation induced
      caspase-3 activation and apoptosis in association with ER and mitochondria
      dysfunction, which were inhibited by zinc as low as 10 MUM but not by 2 mM NAC.
      These results suggest that chronic ethanol exposure induced in ER and
      mitochondrial zinc deficiency might activate intrinsic cell death signaling
      pathway, which could not be effectively rescued by antioxidant treatment.

PMID- 25767262
TI  - Animal models of gastrointestinal and liver diseases. Animal models of visceral
      pain: pathophysiology, translational relevance, and challenges.
AB  - Visceral pain describes pain emanating from the thoracic, pelvic, or abdominal
      organs. In contrast to somatic pain, visceral pain is generally vague, poorly
      localized, and characterized by hypersensitivity to a stimulus such as organ
      distension. Animal models have played a pivotal role in our understanding of the
      mechanisms underlying the pathophysiology of visceral pain. This review focuses
      on animal models of visceral pain and their translational relevance. In addition,
      the challenges of using animal models to develop novel therapeutic approaches to
      treat visceral pain will be discussed. 

PMID- 25767263
TI  - Invited commentary: driving for further evolution.
AB  - The concept of translational cancer epidemiology has evolved since its early
      beginnings in 1937 with the establishment of the National Cancer Institute.
      Conceptual models of cancer control research have also evolved over the last 30
      years, to the point where we now have 4 stages of translational research (T0-T4).
      The current review by Lam et al. (Am J Epidemiol. 2015;181(7):451-458) covers
      cancer epidemiology research supported by the National Cancer Institute and a
      selected sample of the cancer epidemiology literature. It suggests that most
      cancer epidemiology in the last 10 years has been in pure discovery research.
      Current "drivers" of cancer epidemiology research, including new technologies,
      team science multilevel research, and knowledge integration, are not strongly
      represented in the review. However, the use of epidemiology in the latter stages
      of translation may not have been captured by the scope of this review. The closer
      epidemiologists get to advanced stages of translation, the more likely they are
      to work with investigators in other disciplines in other sectors of society. An
      argument can be made that regardless of whether this kind of research is not
      happening or was just missed by the current review, the field of cancer
      epidemiology can expand its scope and further evolve towards more effective
      applications in population health. 

PMID- 25767264
TI  - Lam et al. respond to "Driving for further evolution".

PMID- 25767265
TI  - Evolution of the "drivers" of translational cancer epidemiology: analysis of
      funded grants and the literature.
AB  - Concurrently with a workshop sponsored by the National Cancer Institute, we
      identified key "drivers" for accelerating cancer epidemiology across the
      translational research continuum in the 21st century: emerging technologies, a
      multilevel approach, knowledge integration, and team science. To map the
      evolution of these "drivers" and translational phases (T0-T4) in the past decade,
      we analyzed cancer epidemiology grants funded by the National Cancer Institute
      and published literature for 2000, 2005, and 2010. For each year, we evaluated
      the aims of all new/competing grants and abstracts of randomly selected PubMed
      articles. Compared with grants based on a single institution, consortium-based
      grants were more likely to incorporate contemporary technologies (P = 0.012),
      engage in multilevel analyses (P = 0.010), and incorporate elements of knowledge
      integration (P = 0.036). Approximately 74% of analyzed grants and publications
      involved discovery (T0) or characterization (T1) research, suggesting a need for
      more translational (T2-T4) research. Our evaluation indicated limited research in
      1) a multilevel approach that incorporates molecular, individual, social, and
      environmental determinants and 2) knowledge integration that evaluates the
      robustness of scientific evidence. Cancer epidemiology is at the cusp of a
      paradigm shift, and the field will need to accelerate the pace of translating
      scientific discoveries in order to impart population health benefits. While multi
      institutional and technology-driven collaboration is happening, concerted efforts
      to incorporate other key elements are warranted for the discipline to meet future
      challenges.

PMID- 25767266
TI  - Incidence of Secondary Intra-articular Injuries With Time to Anterior Cruciate
      Ligament Reconstruction.
AB  - BACKGROUND: Precise locations of chondral and meniscal damage with increased time
      to anterior cruciate ligament reconstruction (ACLR) have not been well described.
      PURPOSE/HYPOTHESIS: The purpose of the study was to determine the relationship
      between delay in primary ACLR and incidence of secondary intra-articular injury.
      The hypothesis was that patients with increased time between initial injury and
      ACLR will exhibit greater incidence of secondary intra-articular injury when
      compared with those who receive surgical intervention promptly after injury. A
      second hypothesis was that patients with higher preinjury activity levels or
      older age will exhibit greater secondary injury when compared with those with
      minimal preinjury activity levels and younger age. STUDY DESIGN: Cohort study;
      Level of evidence, 3. METHODS: A retrospective review was performed on 1434
      patients with an anterior cruciate ligament deficiency who underwent primary ACLR
      at a single institution between 2009 and 2013. Patients were grouped according to
      time to surgery after initial injury: 0-3, 4-12, and >12 months. Operative notes
      were used to analyze 10 variables across time-to-surgery groups: cartilage damage
      in the patella, trochlea, medial femoral condyle, lateral femoral condyle, medial
      tibial plateau, and lateral tibial plateau; medial and lateral meniscal injury;
      and the incidence of procedures involving either the meniscus or cartilage.
      Patient age and preinjury activity level were also analyzed for the 10 variables
      based on time-to-surgery groups. RESULTS: An association was noted between time
      to surgery and increased incidence of injury in the trochlea, lateral femoral
      condyle, medial tibial plateau, and medial meniscus (P < .001). Different
      significant findings within each age group were observed, but overall positive
      findings were seen in the same 4 locations described above. On the basis of
      preinjury activity level, the less active patients were most at risk for medial
      meniscal and trochlear injury, while the more active patients were most at risk
      for medial tibial plateau injury with increased time from injury to ACLR.
      CONCLUSION: Increasing time from injury to ACLR was associated with increased
      incidence of secondary injury seen in the trochlea, lateral femoral condyle,
      medial tibial plateau, and medial meniscus. Separate analyses of patient age and
      preinjury activity level showed similar findings, thus supporting the primary
      analysis.

PMID- 25767261
TI  - Novel insights into the function and dynamics of extracellular matrix in liver
      fibrosis.
AB  - Emerging evidence suggests that altered components and posttranslational
      modifications of proteins in the extracellular matrix (ECM) may both initiate and
      drive disease progression. The ECM is a complex grid consisting of multiple
      proteins, most of which play a vital role in containing the essential information
      needed for maintenance of a sophisticated structure anchoring the cells and
      sustaining normal function of tissues. Therefore, the matrix itself may be
      considered as a paracrine/endocrine entity, with more complex functions than
      previously appreciated. The aims of this review are to 1) explore key structural
      and functional components of the ECM as exemplified by monogenetic disorders
      leading to severe pathologies, 2) discuss selected pathological posttranslational
      modifications of ECM proteins resulting in altered functional (signaling)
      properties from the original structural proteins, and 3) discuss how these
      findings support the novel concept that an increasing number of components of the
      ECM harbor signaling functions that can modulate fibrotic liver disease. The ECM
      entails functions in addition to anchoring cells and modulating their migratory
      behavior. Key ECM components and their posttranslational modifications often
      harbor multiple domains with different signaling potential, in particular when
      modified during inflammation or wound healing. This signaling by the ECM should
      be considered a paracrine/endocrine function, as it affects cell phenotype,
      function, fate, and finally tissue homeostasis. These properties should be
      exploited to establish novel biochemical markers and antifibrotic treatment
      strategies for liver fibrosis as well as other fibrotic diseases. 

PMID- 25767267
TI  - Platelet-Rich Plasma Reduces Retear Rates After Arthroscopic Repair of Small- and
      Medium-Sized Rotator Cuff Tears but Is Not Cost-Effective.
AB  - BACKGROUND: It has been suggested that platelet-rich plasma (PRP) improves
      healing after arthroscopic rotator cuff repair. The current literature provides
      ample but inconsistent data on this topic. PURPOSE: To systematically review the
      current in vivo evidence for the use of platelet concentrates (PRP) in the
      arthroscopic treatment of rotator cuff tears to assess effectiveness, safety, and
      cost-effectiveness. STUDY DESIGN: Meta-analysis and cost-effectiveness analysis.
      METHODS: Published evidence from controlled, human trials of rotator cuff repair
      augmented with platelet concentrates was systematically gathered, and data on
      retear rates were extracted. Mathematical and clinical heterogeneity was
      evaluated, and fixed-effect meta-analysis was performed to calculate the risk
      ratio (RR) of retears and the number needed to treat (NNT). Subgroup analyses
      were made for small/medium tears (n = 404) and large/massive tears (n = 374).
      Cost-effectiveness was assessed using data from this meta-analysis and using cost
      data from the literature, including extensive sensitivity analyses, to calculate
      the incremental cost-effectiveness ratio (ICER). RESULTS: Thirteen studies
      published between 2010 and 2014 were identified for analysis. The RR for retear
      for all patients was 0.87 (95% CI, 0.67-1.12; P = .286). For small- and medium
      sized tears (<3 cm), the RR for retear was 0.60 (95% CI, 0.37-0.97), consistent
      with a significant difference in favor of PRP use (P = .038). This translated
      into an NNT of 14 (95% CI, 7-125). However, at an ICER of US$127,893 per quality
      adjusted life year gained, assuming a 5% revision rate, the use of PRP was not
      cost-effective for small- and medium-sized tears. CONCLUSION: In large tears,
      even with double-row repair, the beneficial effects of PRP alone are insufficient
      to compensate the progressed tissue damage. The study data suggest that PRP may
      promote healing of small- and medium-sized tears to reduce retear rates. However,
      despite the substantial biological effect, at current cost, the use of PRP is not
      cost-effective in arthroscopic repair of small- and medium-sized tears.

PMID- 25767268
TI  - Injuries and illnesses in the preparticipation evaluation data of 1693 college
      student-athletes.
AB  - BACKGROUND: While the preparticipation evaluation (PPE) is widely used by medical
      practitioners, its overall effectiveness is unknown, in part because there are no
      standardized or centralized mechanisms to collect and analyze medical history
      information. PURPOSE: To report on the injuries and illnesses identified with the
      use of an electronic PPE (ePPE) completed by first-time National Collegiate
      Athletic Association Division 1 varsity sport participants (N = 1693; 797 women,
      896 men) upon entry to a single institution between 2010 and 2013. STUDY DESIGN:
      Cross-sectional study; Level of evidence, 3. RESULTS: In total, 3126 discrete
      past injuries were reported (women, 1473 injuries; men, 1653 injuries). Time loss
      from sport participation averaged 31.4 days for each injury (women, 32.2 days;
      men, 30.7 days), and aggregate time loss from sport for all student-athletes
      before the ePPE was 256 years. Eleven percent of student-athletes had injuries
      that were unresolved and still symptomatic at the time of the ePPE. Thirty
      percent of injured student-athletes had a history of >=1 surgeries for an injury
      (women, 176; men, 213), and these accounted for 57% of the time lost from sport
      before college participation. Head injuries accounted for 9% (110 women, 173
      men), and loss of consciousness was reported in 19% of these. One in 3 student
      athletes answered "yes" to >=1 of the American Heart Association questions on
      cardiovascular health. While 15% of women reported a history of stress fracture,
      only 3% reported a diagnosed eating disorder. CONCLUSION: While some data in this
      population are self-evident, we were not aware of the high frequency of past
      injuries, the magnitude of time lost from sport, the high frequency of past
      surgery, and the number of participants still symptomatic from injuries. The ePPE
      is a valuable tool for collecting and analyzing aggregate injury and illness data
      in athletes, such as the finding that 11% of injuries that were reported were
      unresolved and still symptomatic.

PMID- 25767269
TI  - Biomechanical comparison of 2 anterior cruciate ligament graft preparation
      techniques for tibial fixation: adjustable-length loop cortical button or
      interference screw.
AB  - BACKGROUND: Cortical button fixation at the femoral side and interference screws
      within the tibial bone tunnel are widely used for anterior cruciate ligament
      graft fixation. Using a bone socket instead of a full tunnel allows cortical
      button fixation on the tibial side as well. If adjustable-length loop cortical
      button devices are used for femoral and tibial fixation, the tendon graft has to
      be secured with sutures in a closed tendon loop. The increased distance of
      fixation points and potential slippage of the tendon strands at the securing
      sutures might lead to greater risk of postoperative graft elongation when
      compared with conventional graft preparation with tibial interference screw
      fixation. HYPOTHESIS: Compared with an anterior cruciate ligament graft with
      tibial adjustable-length loop cortical button fixation, a graft with tibial
      interference screw fixation will show less graft elongation during cyclic loading
      and lower ultimate failure loads. STUDY DESIGN: Controlled laboratory study.
      METHODS: Grafts with tibial adjustable-length loop cortical button fixation and
      grafts with tibial interference screw fixation were biomechanically tested in
      calf tibiae (n = 10 per group). Femoral fixation was equivalent for both groups,
      using an adjustable-length loop cortical button. Specimens underwent cyclic
      loading followed by a load-to-failure test. RESULTS: Grafts with screw fixation
      showed significantly less initial elongation (cycles 1-5: 1.46 +/- 0.26 mm),
      secondary elongation (cycles 6-1000: 1.87 +/- 0.67 mm), and total elongation
      (cycles 1-1000: 3.33 +/- 0.83 mm) in comparison with grafts with button fixation
      (2.47 +/- 0.26, 3.56 +/- 0.39, and 6.03 +/- 0.61 mm, respectively) (P < .001).
      While pull-out stiffness was significantly higher for grafts with screw fixation
      (309.5 +/- 33.2 vs 185.6 +/- 16.4 N/mm) (P < .001), grafts with button fixation
      were able to withstand significantly higher ultimate failure loads (908 +/- 74 vs
      693 +/- 119 N) (P < .001). CONCLUSION: Grafts with tibial adjustable-length loop
      cortical button fixation resulted in higher graft elongation during cyclic
      loading and showed higher ultimate failure loads in comparison with conventional
      graft preparation with tibial interference screw fixation at time zero. CLINICAL
      RELEVANCE: The results of this biomechanical study suggest that grafts with
      tibial interference screw fixation provide better knee stability at time zero
      because of reduced graft elongation and greater stiffness in comparison with
      grafts with tibial adjustable-length loop cortical button fixation.

PMID- 25767270
TI  - ATG16L1 Expression in Carotid Atherosclerotic Plaques Is Associated With Plaque
      Vulnerability.
AB  - OBJECTIVE: Autophagy has emerged as a cell survival mechanism critical for
      cellular homeostasis, which may play a protective role in atherosclerosis.
      ATG16L1, a protein essential for early stages of autophagy, has been implicated
      in the pathogenesis of Crohn's disease. However, it is unknown whether ATG16L1 is
      involved in atherosclerosis. Our aim was to analyze ATG16L1 expression in carotid
      atherosclerotic plaques in relation to markers of plaque vulnerability. APPROACH
      AND RESULTS: Histological analysis of 143 endarterectomized human carotid
      atherosclerotic plaques revealed that ATG16L1 was expressed in areas surrounding
      the necrotic core and the shoulder regions. Double immunofluorescence labeling
      revealed that ATG16L1 was abundantly expressed in phagocytic cells (CD68),
      endothelial cells (CD31), and mast cells (tryptase) in human advanced plaques.
      ATG16L1 immunogold labeling was predominantly observed in endothelial cells and
      foamy smooth muscle cells of the plaques. ATG16L1 protein expression correlated
      with plaque content of proinflammatory cytokines and matrix metalloproteinases.
      Analysis of Atg16L1 at 2 distinct stages of the atherothrombotic process in a
      murine model of plaque vulnerability by incomplete ligation and cuff placement in
      carotid arteries of apolipoprotein-E-deficient mice revealed a strong
      colocalization of Atg16L1 and smooth muscle cells only in early atherosclerotic
      lesions. An increase in ATG16L1 expression and autophagy flux was observed during
      foam cell formation in human macrophages using oxidized-LDL. CONCLUSIONS: Taken
      together, this study shows that ATG16L1 protein expression is associated with
      foam cell formation and inflamed plaque phenotype and could contribute to the
      development of plaque vulnerability at earlier stages of the atherogenic process.

PMID- 25767271
TI  - Clinical experience with novel oral anticoagulants for thromboprophylaxis after
      elective hip and knee arthroplasty.
AB  - Anticoagulant medications help to reduce the risk of thromboembolic events after
      total hip arthroplasty and total knee arthroplasty. Traditionally, this has been
      accomplished with medications, such as low-molecular-weight heparin and warfarin.
      However, these traditional anticoagulants possess a variety of shortcomings that
      leave much room for improvement. A new class of oral anticoagulants is now
      available, and present a more convenient option for safe and efficacious
      thromboprophylaxis in post arthroplasty patients, particularly in the outpatient
      setting. This review focuses on the direct thrombin inhibitor, dabigatran, and
      the selective factor Xa inhibitors, rivaroxaban and apixaban, and the clinical
      data to date about their use in total hip arthroplasty and total knee
      arthroplasty patients. 

PMID- 25767272
TI  - Deletion of Myeloid GSK3alpha Attenuates Atherosclerosis and Promotes an M2
      Macrophage Phenotype.
AB  - OBJECTIVE: Glycogen synthase kinase (GSK)-3alpha/beta has been implicated in the
      pathogenesis of diabetes mellitus, cancer, Alzheimer, and atherosclerosis. The
      tissue- and homolog-specific functions of GSK3alpha and beta in atherosclerosis
      are unknown. This study examines the effect of hepatocyte or myeloid cell
      deletion of GSK3alpha or GSK3beta on atherosclerosis in low-density lipoprotein
      receptor (LDLR)(-/-) mice. APPROACH AND RESULTS: We ablated GSK3alpha or GSK3beta
      expression in hepatic or myeloid cells of LDLR(-/-) mice, and mice were fed a
      high-fat diet for 10 weeks. GSK3alpha or GSK3beta deficiency in hepatic or
      myeloid cells did not affect metabolic parameters, including plasma lipid levels.
      Hepatic deletion of GSK3alpha or GSK3beta did not affect the development of
      atherosclerosis or hepatic lipid content. Myeloid deletion of GSK3alpha, but not
      of GSK3beta, reduced atherosclerotic lesion volume and lesion complexity. Mice
      lacking GSK3alpha in myeloid cells had a less inflammatory and more anti
      inflammatory plasma cytokine profile. Macrophages within atherosclerotic lesions
      of myeloid GSK3alpha-deficient mice, but not of GSK3beta-deficient mice,
      displayed reduced expression of markers associated with M1 macrophage
      polarization and enhanced expression of the M2 markers. Finally, bone marrow
      derived macrophages were isolated and differentiated into classical M1
      macrophages or alternative M2 macrophages in vitro. GSK3alpha deletion, but not
      GSK3beta deletion, attenuated the expression of genes associated with M1
      polarization while promoting the expression of genes associated with M2
      polarization by modulating STAT3 and STAT6 activation. CONCLUSIONS: Our findings
      suggest that deletion of myeloid GSK3alpha attenuates the progression of
      atherosclerosis by promoting an M2 macrophage phenotype.

PMID- 25767273
TI  - Absence of Four-and-a-Half LIM Domain Protein 2 Decreases Atherosclerosis in ApoE
      /- Mice.
AB  - OBJECTIVE: Four-and-a-half LIM domain protein-2 (FHL2) is expressed in
      endothelial cells, vascular smooth muscle cells, and leukocytes. It regulates
      cell survival, migration, and inflammatory response, but its role in
      atherogenesis is unknown. APPROACH AND RESULTS: To investigate the role of FHL2
      in atherosclerosis, FHL2-deficient mice were crossed with ApoE-deficient mice, to
      generate ApoE/FHL2-/- mice. After high-fat diet, ApoE/FHL2-/- mice had
      significantly smaller atherosclerotic plaques than ApoE-/- mice in the aortic
      sinus, the brachiocephalic artery, and the aorta. This was associated with
      enhanced collagen and smooth muscle cell contents and a 2-fold reduction in
      macrophage content within the plaques of ApoE/FHL-2-/- versus ApoE-/- mice. This
      could be explained, in part, by the reduction in aortic ICAM-1 (intracellular
      adhesion molecule) mRNA and VCAM-1 (vascular cell adhesion molecule) protein
      expression in the plaque. Aortic gene expression of the chemokines CX3CL1 and
      CCL5 was increased in ApoE/FHL2-/- versus ApoE-/- mice. Peritoneal thioglycollate
      injection elicited equivalent numbers of monocytes and macrophages in both
      groups, but a significantly lower number of proinflammatory Ly6C high monocytes
      were recruited in ApoE/FHL2-/- versus ApoE-/- mice. Furthermore, mRNA levels of
      CX3CR1 were 2-fold higher in monocytes from ApoE/FHL2-/- versus ApoE-/- mice.
      Finally, we investigated the potential importance of myeloid cell FHL2 deficiency
      in atherosclerosis. After being irradiated, ApoE-/- or ApoE/FHL2-/- mice were
      transplanted with ApoE-/- or ApoE/FHL2-/- bone marrow. After high-fat diet, both
      chimeric groups developed smaller plaques than ApoE-/- transplanted with ApoE-/-
      bone marrow. CONCLUSIONS: These results suggest that FHL2 in both myeloid and
      vascular cells may play an important role in atherosclerosis by promoting
      proinflammatory chemokine production, adhesion molecule expression, and
      proinflammatory monocyte recruitment.

PMID- 25767274
TI  - Endothelial Jagged1 antagonizes Dll4 regulation of endothelial branching and
      promotes vascular maturation downstream of Dll4/Notch1.
AB  - OBJECTIVE: Notch signaling controls cardiovascular development and has been
      associated with several pathological conditions. Among its ligands, Jagged1 and
      Dll4 were shown to have opposing effects in developmental angiogenesis, but the
      underlying mechanism and the role of Jagged1/Notch signaling in adult
      angiogenesis remain incompletely understood. The current study addresses the
      importance of endothelial Jagged1-mediated Notch signaling in the context of
      adult physiological angiogenesis and the interactions of Jagged1 and Dll4 on
      angiogenic response and vascular maturation processes. APPROACH AND RESULTS: The
      role of endothelial Jagged1 in wound healing kinetics and angiogenesis was
      investigated with endothelial-specific Jag1 gain-of-function and loss-of-function
      mouse mutants (eJag1OE and eJag1cKO). To study the interactions between the 2
      Notch ligands, genetic mouse models were combined with pharmacological inhibition
      of Dll4 or Jagged1, respectively. Jagged1 overexpression in endothelial cells
      increased vessel density, maturation, and perfusion, thus accelerating wound
      healing. The opposite effect was seen in eJag1cKO animals. Interestingly, Dll4
      blockade in these animals led to an increase in vascular density but induced a
      greater decrease in perivascular cell coverage. However, Jagged1 inhibition in
      Dll4 gain-of-function (eDll4OE) mutants, with reduced angiogenesis, further
      diminished angiogenic growth and hampered perivascular cell coverage. Our
      findings suggest that as Dll4 blocks endothelial activation through Notch1
      signaling, it also induces Jagged1 expression. Jagged1 then blocks Dll4 signaling
      through Notch1, allowing endothelial activation by vascular endothelial growth
      factor and endothelial layer growth. Jagged1 also initiates maturation of the
      newly formed vessels, possibly by binding and activating endothelial Notch4.
      Importantly, mice administered with a Notch4 agonistic antibody mimicked the
      mural cell phenotype of eJag1OE mutants without affecting angiogenic growth,
      which is thought to be Notch1 dependent. CONCLUSIONS: Endothelial Jagged1 is
      likely to operate downstream of Dll4/Notch1 signaling to activate Notch4 and
      regulate vascular maturation. Thus, Jagged1 not only counteracts Dll4/Notch in
      the endothelium but also generates a balance between angiogenic growth and
      maturation processes in vivo.

PMID- 25767275
TI  - Collectivization of Vascular Smooth Muscle Cells via TGF-beta-Cadherin-11
      Dependent Adhesive Switching.
AB  - OBJECTIVE: Smooth muscle cells (SMCs) in healthy arteries are arranged as a
      collective. However, in diseased arteries, SMCs commonly exist as individual
      cells, unconnected to each other. The purpose of this study was to elucidate the
      events that enable individualized SMCs to enter into a stable and interacting
      cell collective. APPROACH AND RESULTS: Human SMCs stimulated to undergo
      programmed collectivization were tracked by time-lapse microscopy. We uncovered a
      switch in the behavior of contacting SMCs from semiautonomous motility to cell
      cell adherence. Central to the cell-adherent phenotype was the formation of
      uniquely elongated adherens junctions, up to 60 MUm in length, which appeared to
      strap adjacent SMCs to each other. Remarkably, these junctions contained both N
      cadherin and cadherin-11. Ground-state depletion super-resolution microscopy
      revealed that these hybrid assemblies were comprised of 2 parallel nanotracks of
      each cadherin, separated by 50 nm. Blocking either N-cadherin or cadherin-11
      inhibited collectivization. Cell-cell adhesion and adherens junction elongation
      were associated with reduced transforming growth factor-beta signaling, and
      exogenous transforming growth factor-beta1 suppressed junction elongation via the
      noncanonical p38 pathway. Imaging of fura-2-loaded SMCs revealed that SMC
      assemblies displayed coordinated calcium oscillations and cell-cell transmission
      of calcium waves which, together with increased connexin 43-containing junctions,
      depended on cadherin-11 and N-cadherin function. CONCLUSIONS: SMCs can self
      organize, structurally and functionally, via transforming growth factor-beta-p38
      dependent adhesive switching and a novel adherens junction architecture comprised
      of hybrid nanotracks of cadherin-11 and N-cadherin. The findings define a
      mechanism for the assembly of SMCs into networks, a process that may be relevant
      to the stability and function of blood vessels.

PMID- 25767276
TI  - Light to Moderate Alcohol Consumption Is Associated With Lower Risk of Aortic
      Valve Sclerosis: The Study of Health in Pomerania (SHIP).
AB  - OBJECTIVE: In developed countries, sclerotic and calcific degeneration of the
      aortic valve is a common disorder showing pathophysiologic similarities with
      atherothrombotic coronary disease. Light to moderate alcohol consumption has been
      associated with a lower risk for atherothrombotic coronary disease and mortality.
      Whether alcohol consumption affects the development of aortic valve sclerosis
      (AVS) is not well known. In the present study, we aim to analyze the cross
      sectional association between average daily alcohol consumption and AVS in the
      general population. APPROACH AND RESULTS: We analyzed cross-sectional data from
      2022 men and women, aged 45 to 81 years, from the population-based Study of
      Health in Pomerania. We used a computer-assisted interview that included beverage
      specific questions about quantity and frequency of alcohol over the last 30 days
      to calculate the average quantity of alcohol consumption (in grams of ethanol per
      day). AVS was ascertained by echocardiography. The prevalence of AVS was 32.3%.
      Average daily alcohol intake displayed a J-type relation with AVS (fully adjusted
      P value: 0.005). Compared with individuals with an average consumption of 10 g of
      alcohol per day, multivariable-adjusted odds ratios were 1.60 (95% confidence
      interval, 1.19-2.14) among current abstainers and 1.56 (95% confidence interval,
      1.01-2.41) among individuals with an average consumption of 60 g per day.
      CONCLUSIONS: Our findings indicate that light to moderate alcohol consumption was
      associated with a lower odd of having AVS. Prospective data need to address
      whether alcohol consumption and related changes over time in several biological
      markers affect the progression of AVS.

PMID- 25767278
TI  - Digestive bleeding in a Georgian liver transplant recipient.

PMID- 25767277
TI  - FKBPL is a critical antiangiogenic regulator of developmental and pathological
      angiogenesis.
AB  - OBJECTIVE: The antitumor effects of FK506-binding protein like (FKBPL) and its
      extracellular role in angiogenesis are well characterized; however, its role in
      physiological/developmental angiogenesis and the effect of FKBPL ablation has not
      been evaluated. This is important as effects of some angiogenic proteins are
      dosage dependent. Here we evaluate the regulation of FKBPL secretion under
      angiogenic stimuli, as well as the effect of FKBPL ablation in angiogenesis using
      mouse and zebrafish models. APPROACH AND RESULTS: FKBPL is secreted maximally by
      human microvascular endothelial cells and fibroblasts, and this was specifically
      downregulated by proangiogenic hypoxic signals, but not by the angiogenic
      cytokines, VEGF or IL8. FKBPL's critical role in angiogenesis was supported by
      our inability to generate an Fkbpl knockout mouse, with embryonic lethality
      occurring before E8.5. However, whilst Fkbpl heterozygotic embryos showed some
      vasculature irregularities, the mice developed normally. In murine angiogenesis
      models, including the ex vivo aortic ring assay, in vivo sponge assay, and tumor
      growth assay, Fkbpl(+/-) mice exhibited increased sprouting, enhanced vessel
      recruitment, and faster tumor growth, respectively, supporting the antiangiogenic
      function of FKBPL. In zebrafish, knockdown of zFkbpl using morpholinos disrupted
      the vasculature, and the phenotype was rescued with hFKBPL. Interestingly, this
      vessel disruption was ineffective when zcd44 was knocked-down, supporting the
      dependency of zFkbpl on zCd44 in zebrafish. CONCLUSIONS: FKBPL is an important
      regulator of angiogenesis, having an essential role in murine and zebrafish blood
      vessel development. Mouse models of angiogenesis demonstrated a proangiogenic
      phenotype in Fkbpl heterozygotes.

PMID- 25767280
TI  - Introduction to a compendium on hypertension.

PMID- 25767281
TI  - The epidemiology of blood pressure and its worldwide management.
AB  - Despite the vast amount of evidence on the benefits of blood pressure lowering
      accumulated to date, elevated blood pressure is still the leading risk factor for
      disease and disability worldwide. The purpose of this review is to summarize the
      epidemiological evidence underpinning the association between blood pressure and
      a range of conditions. This review focuses on the association between systolic
      and diastolic blood pressures and the risk of cardiovascular and renal disease.
      Evidence for and against the existence of a J-shaped curve association between
      blood pressure and cardiovascular risk, and differences in the predictive power
      of systolic, diastolic, and pulse pressure, are described. In addition, global
      and regional trends in blood pressure levels and management of hypertension are
      reviewed. 

PMID- 25767282
TI  - Genetic and molecular aspects of hypertension.
AB  - Until recently, significant advances in our understanding of the mechanisms of
      blood pressure regulation arose from studies of monogenic forms of hypertension
      and hypotension, which identified rare variants that primarily alter renal salt
      handling. Genome-wide association and exome sequencing studies over the past 6
      years have resulted in an unparalleled burst of discovery in the genetics of
      blood pressure regulation and hypertension. More importantly, genome-wide
      association studies, while expanding the list of common genetic variants
      associated with blood pressure and hypertension, are also uncovering novel
      pathways of blood pressure regulation that augur a new era of novel drug
      development, repurposing, and stratification in the management of hypertension.
      In this review, we describe the current state of the art of the genetic and
      molecular basis of blood pressure and hypertension. 

PMID- 25767283
TI  - Hypertension: renin-angiotensin-aldosterone system alterations.
AB  - Blockers of the renin-angiotensin-aldosterone system (RAAS), that is, renin
      inhibitors, angiotensin (Ang)-converting enzyme (ACE) inhibitors, Ang II type 1
      receptor antagonists, and mineralocorticoid receptor antagonists, are a
      cornerstone in the treatment of hypertension. How exactly they exert their
      effect, in particular in patients with low circulating RAAS activity, also taking
      into consideration the so-called Ang II/aldosterone escape that often occurs
      after initial blockade, is still incompletely understood. Multiple studies have
      tried to find parameters that predict the response to RAAS blockade, allowing a
      personalized treatment approach. Consequently, the question should now be
      answered on what basis (eg, sex, ethnicity, age, salt intake, baseline renin, ACE
      or aldosterone, and genetic variance) a RAAS blocker can be chosen to treat an
      individual patient. Are all blockers equal? Does optimal blockade imply maximum
      RAAS blockade, for example, by combining >=2 RAAS blockers or by simply
      increasing the dose of 1 blocker? Exciting recent investigations reveal a range
      of unanticipated extrarenal effects of aldosterone, as well as a detailed insight
      in the genetic causes of primary aldosteronism, and mineralocorticoid receptor
      blockers have now become an important treatment option for resistant
      hypertension. Finally, apart from the deleterious ACE-Ang II-Ang II type 1
      receptor arm, animal studies support the existence of protective aminopeptidase A
      Ang III-Ang II type 2 receptor and ACE2-Ang-(1 to 7)-Mas receptor arms, paving
      the way for multiple new treatment options. This review provides an update about
      all these aspects, critically discussing the many controversies and allowing the
      reader to obtain a full understanding of what we currently know about RAAS
      alterations in hypertension. 

PMID- 25767284
TI  - The sympathetic nervous system alterations in human hypertension.
AB  - Several articles have dealt with the importance and mechanisms of the sympathetic
      nervous system alterations in experimental animal models of hypertension. This
      review addresses the role of the sympathetic nervous system in the
      pathophysiology and therapy of human hypertension. We first discuss the strengths
      and limitations of various techniques for assessing the sympathetic nervous
      system in humans, with a focus on heart rate, plasma norepinephrine,
      microneurographic recording of sympathetic nerve traffic, and measurements of
      radiolabeled norepinephrine spillover. We then examine the evidence supporting
      the importance of neuroadrenergic factors as promoters and amplifiers of human
      hypertension. We expand on the role of the sympathetic nervous system in 2
      increasingly common forms of secondary hypertension, namely hypertension
      associated with obesity and with renal disease. With this background, we examine
      interventions of sympathetic deactivation as a mode of antihypertensive
      treatment. Particular emphasis is given to the background and results of recent
      therapeutic approaches based on carotid baroreceptor stimulation and
      radiofrequency ablation of the renal nerves. 

PMID- 25767286
TI  - The structural factor of hypertension: large and small artery alterations.
AB  - Pathophysiological studies have extensively investigated the structural factor in
      hypertension, including large and small artery remodeling and functional changes.
      Here, we review the recent literature on the alterations in small and large
      arteries in hypertension. We discuss the possible mechanisms underlying these
      abnormalities and we explain how they accompany and often precede hypertension.
      Finally, we propose an integrated pathophysiological approach to better
      understand how the cross-talk between large and small artery changes interacts in
      pressure wave transmission, exaggerates cardiac, brain and kidney damage, and
      lead to cardiovascular and renal complications. We focus on patients with
      essential hypertension because this is the most prevalent form of hypertension,
      and describe other forms of hypertension only for contrasting their
      characteristics with those of uncomplicated essential hypertension. 

PMID- 25767285
TI  - Obesity-induced hypertension: interaction of neurohumoral and renal mechanisms.
AB  - Excess weight gain, especially when associated with increased visceral adiposity,
      is a major cause of hypertension, accounting for 65% to 75% of the risk for human
      primary (essential) hypertension. Increased renal tubular sodium reabsorption
      impairs pressure natriuresis and plays an important role in initiating obesity
      hypertension. The mediators of abnormal kidney function and increased blood
      pressure during development of obesity hypertension include (1) physical
      compression of the kidneys by fat in and around the kidneys, (2) activation of
      the renin-angiotensin-aldosterone system, and (3) increased sympathetic nervous
      system activity. Activation of the renin-angiotensin-aldosterone system is likely
      due, in part, to renal compression, as well as sympathetic nervous system
      activation. However, obesity also causes mineralocorticoid receptor activation
      independent of aldosterone or angiotensin II. The mechanisms for sympathetic
      nervous system activation in obesity have not been fully elucidated but may
      require leptin and activation of the brain melanocortin system. With prolonged
      obesity and development of target organ injury, especially renal injury, obesity
      associated hypertension becomes more difficult to control, often requiring
      multiple antihypertensive drugs and treatment of other risk factors, including
      dyslipidemia, insulin resistance and diabetes mellitus, and inflammation. Unless
      effective antiobesity drugs are developed, the effect of obesity on hypertension
      and related cardiovascular, renal and metabolic disorders is likely to become
      even more important in the future as the prevalence of obesity continues to
      increase. 

PMID- 25767288
TI  - Clinical value of ambulatory blood pressure: evidence and limits.
AB  - This article reviews the clinical value of ambulatory blood pressure (BP) vis-a
      vis the traditional BP measurements taken in the physician's office or in the
      hospital. Mention is initially made that longitudinal studies conducted in the
      general population or in hypertensive cohorts have shown that ambulatory BP
      provides a more accurate prediction of outcome than office BP. Namely, that (1)
      the risk of cardiovascular events increases in a less steep fashion with office
      than with 24-hour mean BP, (2) the 24-hour BP-dependent prediction is maintained
      after adjustment for office BP values, and (3) among individuals with normal
      office BP, those with increased ambulatory BP (masked hypertension) have an
      increased prevalence of organ damage, a more frequent unfavorable metabolic
      profile and a higher risk of new onset sustained hypertension, diabetes mellitus,
      and cardiovascular events than those with normal ambulatory BP. It is further
      mentioned, however, that more recently similar observations have been made for
      individuals with high office but normal ambulatory BP (white coat hypertension)
      suggesting a complementary role of out-of-office and office BP values in the
      determination of patients' prognosis. The evidence in favor of an independent
      prognostic value also of some within 24-hour BP phenomena (night BP reduction or
      absolute values, short-term BP variations, and morning BP surge) is then
      critically appraised for its elements of strength and weakness. Finally, whether
      the clinical advantages of ambulatory BP make this approach necessary for all
      patients with hypertension is discussed. The conclusion is that this is at
      present still premature because crucial evidence pro or against routine use of
      this approach in untreated and treated hypertensives is not yet available. It
      will be crucial for future studies to determine whether, compared with a
      treatment guided by office BP, a treatment tailored on ambulatory BP allows to
      improve prevention or regression of organ damage as well as protection from major
      cardiovascular complications to a degree that justifies the complexity and cost
      of the procedure. 

PMID- 25767289
TI  - Sodium intake and cardiovascular health.
AB  - Sodium is an essential nutrient. Increasing sodium intake is associated with
      increasing blood pressure, whereas low sodium intake results in increased renin
      and aldosterone levels. Randomized controlled trials have reported reductions in
      blood pressure with reductions in sodium intake, to levels of sodium intake <1.5
      g/d, and form the evidentiary basis for current population-wide guidelines
      recommending low sodium intake. Although low sodium intake (<2.0 g/d) has been
      achieved in short-term feeding clinical trials, sustained low sodium intake has
      not been achieved by any of the longer term clinical trials (>6-month duration).
      It is assumed that the blood pressure-lowering effects of reducing sodium intake
      to low levels will result in large reductions in cardiovascular disease globally.
      However, current evidence from prospective cohort studies suggests a J-shaped
      association between sodium intake and cardiovascular events, based on studies
      from >300 000 people, and suggests that the lowest risk of cardiovascular events
      and death occurs in populations consuming an average sodium intake range (3-5
      g/d). The increased risk of cardiovascular events associated with higher sodium
      intake (>5 g/d) is most prominent in those with hypertension. A major deficit in
      the field is the absence of large randomized controlled trials to provide
      definitive evidence on optimal sodium intake for preventing cardiovascular
      events. Pending such trials, current evidence would suggest a recommendation for
      moderate sodium intake in the general population (3-5 g/d), with targeting the
      lower end of the moderate range among those with hypertension. 

PMID- 25767287
TI  - Inflammation, immunity, and hypertensive end-organ damage.
AB  - For >50 years, it has been recognized that immunity contributes to hypertension.
      Recent data have defined an important role of T cells and various T cell-derived
      cytokines in several models of experimental hypertension. These studies have
      shown that stimuli like angiotensin II, deoxycorticosterone acetate-salt, and
      excessive catecholamines lead to formation of effector like T cells that
      infiltrate the kidney and perivascular regions of both large arteries and
      arterioles. There is also accumulation of monocyte/macrophages in these regions.
      Cytokines released from these cells, including interleukin-17, interferon-gamma,
      tumor necrosis factoralpha, and interleukin-6 promote both renal and vascular
      dysfunction and damage, leading to enhanced sodium retention and increased
      systemic vascular resistance. The renal effects of these cytokines remain to be
      fully defined, but include enhanced formation of angiotensinogen, increased
      sodium reabsorption, and increased renal fibrosis. Recent experiments have
      defined a link between oxidative stress and immune activation in hypertension.
      These have shown that hypertension is associated with formation of reactive
      oxygen species in dendritic cells that lead to formation of gamma ketoaldehydes,
      or isoketals. These rapidly adduct to protein lysines and are presented by
      dendritic cells as neoantigens that activate T cells and promote hypertension.
      Thus, cells of both the innate and adaptive immune system contribute to end-organ
      damage and dysfunction in hypertension. Therapeutic interventions to reduce
      activation of these cells may prove beneficial in reducing end-organ damage and
      preventing consequences of hypertension, including myocardial infarction, heart
      failure, renal failure, and stroke. 

PMID- 25767290
TI  - Randomized controlled trials of blood pressure lowering in hypertension: a
      critical reappraisal.
AB  - Sixty-eight blood pressure (BP)-lowering randomized controlled trials (defined as
      randomized controlled trials comparing active treatment with placebo, or less
      active treatment, achieving a BP difference, performed between 1966 and end 2013
      in cohorts with >= 40% hypertensive patients, and exclusive of trials in acute
      myocardial infarction, heart failure, acute stroke, and dialysis) were identified
      and meta-analyzed grouping the randomized controlled trials on the basis of
      clinically relevant questions: (1) does BP lowering reduce all types of
      cardiovascular outcome? (2) Is prevention of all outcomes proportional to the
      extent of systolic, diastolic, and pulse BP? (3) Have all classes of BP-lowering
      drugs been shown capable of reducing all types of cardiovascular outcome? (4) Is
      BP lowering beneficial when intervention is initiated at any grade (or stage) of
      hypertension? (5) Do BP-lowering randomized controlled trials provide evidence
      about systolic BP and diastolic BP targets of treatment? (6) Should BP-lowering
      treatment be preferentially addressed to patients in higher risk categories
      promising larger absolute treatment benefits? The results of these meta-analyses
      provide further support to current hypertension treatment guidelines by showing
      that BP lowering can significantly reduce major cardiovascular outcomes largely
      independent of the agents used, significant risk reduction is found at all
      hypertension grades (stages), and when systolic BP is lowered below a cut off of
      140 mm Hg with some further reduction limited to stroke at systolic BP values
      just <130 mm Hg. Absolute risk reduction progressively increases higher is total
      cardiovascular risk, but this greater benefit is associated with a progressively
      higher residual risk, ie, higher treatment failures.

PMID- 25767291
TI  - New approaches in the treatment of hypertension.
AB  - Hypertension is the most common modifiable risk factor for cardiovascular disease
      and death, and lowering blood pressure with antihypertensive drugs reduces target
      organ damage and prevents cardiovascular disease outcomes. Despite a plethora of
      available treatment options, a substantial portion of the hypertensive population
      has uncontrolled blood pressure. The unmet need of controlling blood pressure in
      this population may be addressed, in part, by developing new drugs and
      devices/procedures to treat hypertension and its comorbidities. In this
      Compendium Review, we discuss new drugs and interventional treatments that are
      undergoing preclinical or clinical testing for hypertension treatment. New drug
      classes, eg, inhibitors of vasopeptidases, aldosterone synthase and soluble
      epoxide hydrolase, agonists of natriuretic peptide A and vasoactive intestinal
      peptide receptor 2, and a novel mineralocorticoid receptor antagonist are in
      phase II/III of development, while inhibitors of aminopeptidase A, dopamine beta
      hydroxylase, and the intestinal Na(+)/H(+) exchanger 3, agonists of components of
      the angiotensin-converting enzyme 2/angiotensin(1-7)/Mas receptor axis and
      vaccines directed toward angiotensin II and its type 1 receptor are in phase I or
      preclinical development. The two main interventional approaches, transcatheter
      renal denervation and baroreflex activation therapy, are used in clinical
      practice for severe treatment resistant hypertension in some countries. Renal
      denervation is also being evaluated for treatment of various comorbidities, eg,
      chronic heart failure, cardiac arrhythmias and chronic renal failure. Novel
      interventional approaches in early development include carotid body ablation and
      arteriovenous fistula placement. Importantly, none of these novel drug or device
      treatments has been shown to prevent cardiovascular disease outcomes or death in
      hypertensive patients. 

PMID- 25767292
TI  - Iron homeostasis and pulmonary hypertension: iron deficiency leads to pulmonary
      vascular remodeling in the rat.
AB  - RATIONALE: Iron deficiency without anemia is prevalent in patients with
      idiopathic pulmonary arterial hypertension and associated with reduced exercise
      capacity and survival. OBJECTIVES: We hypothesized that iron deficiency is
      involved in the pathogenesis of pulmonary hypertension and iron replacement is a
      possible therapeutic strategy. METHODS AND RESULTS: Rats were fed an iron
      deficient diet (IDD, 7 mg/kg) and investigated for 4 weeks. Iron deficiency was
      evident from depleted iron stores (decreased liver, serum iron, and ferritin),
      reduced erythropoiesis, and significantly decreased transferrin saturation and
      lung iron stores after 2 weeks IDD. IDD rats exhibited profound pulmonary
      vascular remodeling with prominent muscularization, medial hypertrophy, and
      perivascular inflammatory cell infiltration, associated with raised pulmonary
      artery pressure and right ventricular hypertrophy. IDD rat lungs demonstrated
      increased expression of hypoxia-induced factor-1alpha and hypoxia-induced factor
      2alpha, nuclear factor of activated T cells and survivin, and signal transducers
      and activators of transcription-3 activation, which promote vascular cell
      proliferation and resistance to apoptosis. Biochemical examination showed reduced
      mitochondrial complex I activity and mitochondrial membrane hyperpolarization in
      mitochondria from IDD rat pulmonary arteries. Along with upregulation of the
      glucose transporter, glucose transporter 1, and glycolytic genes, hk1 and pdk1,
      lung fluorine-18-labeled 2-fluoro-2-deoxyglucose ligand uptake was significantly
      increased in IDD rats. The hemodynamic and pulmonary vascular remodeling were
      reversed by iron replacement (ferric carboxymaltose, 75 mg/kg) and attenuated in
      the presence of iron deficiency by dichloroacetate and imatinib, 2 putative
      treatments explored for pulmonary arterial hypertension that target aerobic
      glycolysis and proliferation, respectively. CONCLUSIONS: These data suggest a
      major role for iron in pulmonary vascular homeostasis and support the clinical
      evaluation of iron replacement in patients with pulmonary hypertension.

PMID- 25767294
TI  - Improving the consistency of domain annotation within the Conserved Domain
      Database.
AB  - When annotating protein sequences with the footprints of evolutionarily conserved
      domains, conservative score or E-value thresholds need to be applied for RPS
      BLAST hits, to avoid many false positives. We notice that manual inspection and
      classification of hits gathered at a higher threshold can add a significant
      amount of valuable domain annotation. We report an automated algorithm that
      'rescues' valuable borderline-scoring domain hits that are well-supported by
      domain architecture (DA, the sequential order of conserved domains in a protein
      query), including tandem repeats of domain hits reported at a more conservative
      threshold. This algorithm is now available as a selectable option on the public
      conserved domain search (CD-Search) pages. We also report on the possibility to
      'suppress' domain hits close to the threshold based on a lack of well-supported
      DA and to implement this conservatively as an option in live conserved domain
      searches and for pre-computed results. Improving domain annotation consistency
      will in turn reduce the fraction of NR sequences with incomplete DAs.

PMID- 25767295
TI  - Detention, Democracy, and Inequality in a Divided Society.

PMID- 25767293
TI  - AXL Is a Logical Molecular Target in Head and Neck Squamous Cell Carcinoma.
AB  - PURPOSE: Head and neck squamous cell carcinoma (HNSCC) represents the eighth most
      common malignancy worldwide. Standard-of-care treatments for patients with HNSCC
      include surgery, radiation, and chemotherapy. In addition, the anti-EGFR
      monoclonal antibody cetuximab is often used in combination with these treatment
      modalities. Despite clinical success with these therapeutics, HNSCC remains a
      difficult malignancy to treat. Thus, identification of new molecular targets is
      critical. EXPERIMENTAL DESIGN: In the current study, the receptor tyrosine kinase
      AXL was investigated as a molecular target in HNSCC using established cell lines,
      HNSCC patient-derived xenografts (PDX), and human tumors. HNSCC dependency on AXL
      was evaluated with both anti-AXL siRNAs and the small-molecule AXL inhibitor
      R428. Furthermore, AXL inhibition was evaluated with standard-of-care treatment
      regimens used in HNSCC. RESULTS: AXL was found to be highly overexpressed in
      several models of HNSCC, where AXL was significantly associated with higher
      pathologic grade, presence of distant metastases, and shorter relapse-free
      survival in patients with HNSCC. Further investigations indicated that HNSCC
      cells were reliant on AXL for cellular proliferation, migration, and invasion. In
      addition, targeting AXL increased HNSCC cell line sensitivity to chemotherapy,
      cetuximab, and radiation. Moreover, radiation-resistant HNSCC cell line
      xenografts and PDXs expressed elevated levels of both total and activated AXL,
      indicating a role for AXL in radiation resistance. CONCLUSIONS: This study
      provides evidence for the role of AXL in HNSCC pathogenesis and supports further
      preclinical and clinical evaluation of anti-AXL therapeutics for the treatment of
      patients with HNSCC.

PMID- 25767296
TI  - Forced evolution in silico by artificial transposons and their genetic operators:
      The ant navigation problem.
AB  - Modern evolutionary computation utilizes heuristic optimizations based upon
      concepts borrowed from the Darwinian theory of natural selection. Their
      demonstrated efficacy has reawakened an interest in other aspects of contemporary
      biology as an inspiration for new algorithms. However, amongst the many excellent
      candidates for study, contemporary models of biological macroevolution attract
      special attention. We believe that a vital direction in this field must be
      algorithms that model the activity of "genomic parasites", such as transposons,
      in biological evolution. Many evolutionary biologists posit that it is the co
      evolution of populations with their genomic parasites that permits the high
      efficiency of evolutionary searches found in the living world. This publication
      is our first step in the direction of developing a minimal assortment of
      algorithms that simulate the role of genomic parasites. Specifically, we started
      in the domain of genetic algorithms (GA) and selected the Artificial Ant Problem
      as a test case. This navigation problem is widely known as a classical benchmark
      test and possesses a large body of literature. We add new objects to the standard
      toolkit of GA - artificial transposons and a collection of operators that operate
      on them. We define these artificial transposons as a fragment of an ant's code
      with properties that cause it to stand apart from the rest. The minimal set of
      operators for transposons is a transposon mutation operator, and a transposon
      reproduction operator that causes a transposon to multiply within the population
      of hosts. An analysis of the population dynamics of transposons within the course
      of ant evolution showed that transposons are involved in the processes of
      propagation and selection of blocks of ant navigation programs. During this time,
      the speed of evolutionary search increases significantly. We concluded that
      artificial transposons, analogous to real transposons, are truly capable of
      acting as intelligent mutators that adapt in response to an evolutionary problem
      in the course of co-evolution with their hosts.

PMID- 25767297
TI  - Strength Training Improves Body Image and Physical Activity Behaviors Among
      Midlife and Older Rural Women.
AB  - The effect of strength training on body image is understudied. The Strong Women
      Program, a 10-week, twice weekly strength-training program, was provided by
      Extension agents to 341 older rural women (62+/-12 years); changes in body image
      and other psychosocial variables were evaluated. Paired-sample t-test analyses
      were conducted to assess mean differences pre- to post-program. Strength training
      was associated with significant improvements in several dimensions of body image,
      health-related quality of life, and physical activity behaviors, satisfaction,
      and comfort among rural aging women-an often underserved population that stands
      to benefit considerably from similar programs.

PMID- 25767298
TI  - Bioconversion of 6-epi-Notoamide T Produces Metabolites of Unprecedented
      Structures in a Marine-derived Aspergillus sp.
AB  - We previously described the bioconversion of Notoamide T into (+)-Stephacidin A
      and (-)-Notoamide B, which suggested that Versicolamide B (8) is biosynthesized
      from 6-epi-Notoamide T (10) via 6-epi-Stephacidin A. Here we report that [13C]2
      10 was incorporated into isotopically enriched 8 and seven new metabolites, which
      were not produced under normal culture conditions. The results suggest that the
      addition of excess precursor activated the expression of dormant tailoring genes
      giving rise to these structurally unprecedented metabolites.

PMID- 25767299
TI  - Increasing organ donation by presumed consent and allocation priority: Chile.
AB  - Chile, a middle-income country, recently joined Israel and Singapore as the
      world's only countries to require reciprocity as a precondition for organ
      transplantation. The Chilean reform includes opt-out provisions designed to
      foster donation and priority for organ transplantation for registered people.
      Although the reform has had serious difficulties in achieving its mission, it can
      be reviewed by other countries that seek to address the serious shortage of
      organs. As increased organ donation can substantially enhance or save more lives,
      the effect on organ availability due to incentives arising from rules of
      preference should not be underestimated. 

PMID- 25767301
TI  - Agreement to build better scientific journals in Colombia: the San Francisco
      Declaration on Research Assessment.

PMID- 25767300
TI  - Big data in global health: improving health in low- and middle-income countries.
AB  - Over the last decade, a massive increase in data collection and analysis has
      occurred in many fields. In the health sector, however, there has been relatively
      little progress in data analysis and application despite a rapid rise in data
      production. Given adequate governance, improvements in the quality, quantity,
      storage and analysis of health data could lead to substantial improvements in
      many health outcomes. In low- and middle-income countries in particular, the
      creation of an information feedback mechanism can move health-care delivery
      towards results-based practice and improve the effective use of scarce resources.
      We review the evolving definition of big data and the possible advantages of -
      and problems in - using such data to improve health-care delivery in low- and
      middle-income countries. The collection of big data as mobile-phone based
      services improve may mean that development phases required elsewhere can be
      skipped. However, poor infrastructure may prevent interoperability and the safe
      use of patient data. An appropriate governance framework must be developed and
      enforced to protect individuals and ensure that health-care delivery is tailored
      to the characteristics and values of the target communities. 

PMID- 25767302
TI  - NAT2 gene polymorphisms in three indigenous groups in the Colombian Caribbean
      Coast region.
AB  - OBJECTIVE: To study the NAT2 gene polymorphisms 481T, 590A and 857A in the
      Chimila, Wiwa and Wayuu indigenous groups of the Colombian Caribbean to determine
      the frequencies of the alleles NAT2*4, NAT2*5, NAT2*6, and NAT2*7 and to
      determine the types of acetylators present in these populations. METHODS: A total
      of 202 subjects were studied: 47 Chimila, 55 Wiwa, and 100 Wayuu. The
      polymorphisms were identified using a real-time PCR method for allelic
      discrimination designed using Taqman of Applied Biosystems. RESULTS: The
      following alleles were found at the highest frequency in the following groups:
      the NAT2*4 allele (wild type) in the Wayuu group (55.3%), the NAT2*5 allele in
      the Wiwa group (34.5%), and the NAT2*7 allele in the Chimila group (24.2%). A
      higher frequency of the rapid acetylator status was found in the Wayuu group
      (31.3%) and Chimila group (29.5%) compared with the Wiwa group (12.7%). The
      intermediate acetylator status distribution was very similar in all three groups,
      and the frequency of the slow acetylator status was higher in the Wiwa group
      (32.7%) compared with the Chimila and Wayuu groups (20.5% and 21.2%,
      respectively). CONCLUSION: The results demonstrated the allelic distribution and
      pharmacogenetic differences of the three groups studied and revealed the most
      frequent acetylator status and phenotype. Because of the high prevalence of slow
      acetylators, a greater incidence of tuberculosis (TB) drug-induced hepatotoxicity
      is predicted in these populations, with a higher frequency in the Wiwa group.

PMID- 25767303
TI  - Global differential expression of genes located in the Down Syndrome Critical
      Region in normal human brain.
AB  - BACKGROUND: The information of gene expression obtained from databases, have made
      possible the extraction and analysis of data related with several molecular
      processes involving not only in brain homeostasis but its disruption in some
      neuropathologies; principally in Down syndrome and the Alzheimer disease.
      OBJECTIVE: To correlate the levels of transcription of 19 genes located in the
      Down Syndrome Critical Region (DSCR) with their expression in several
      substructures of normal human brain. METHODS: There were obtained expression
      profiles of 19 DSCR genes in 42 brain substructures, from gene expression values
      available at the database of the human brain of the Brain Atlas of the Allen
      Institute for Brain Sciences", (http://human.brain-map.org/). The co-expression
      patterns of DSCR genes in brain were calculated by using multivariate statistical
      methods. RESULTS: Highest levels of gene expression were registered at caudate
      nucleus, nucleus accumbens and putamen among central areas of cerebral cortex.
      Increased expression levels of RCAN1 that encode by a protein involved in signal
      transduction process of the CNS were recorded for PCP4 that participates in the
      binding to calmodulin and TTC3; a protein that is associated with differentiation
      of neurons. That previously identified brain structures play a crucial role in
      the learning process, in different class of memory and in motor skills.
      CONCLUSION: The precise regulation of DSCR gene expression is crucial to maintain
      the brain homeostasis, especially in those areas with high levels of gene
      expression associated with a remarkable process of learning and cognition.

PMID- 25767304
TI  - Characterization of treatment failure in HIV positive patients in the Colombian
      Caribbean region.
AB  - BACKGROUND: Treatment failure (TF) in patients receiving antiretroviral therapy
      against human immunodeficiency virus (HIV) is always a concern. OBJECTIVE: To
      examine the correlates associated with TF in patients living in the Colombian
      Caribbean city of Barranquilla, an aspect that was poorly studied in this region.
      METHODS: Treatment failure was evaluated in a cross-sectional study from
      virological, immunological and clinical standpoints. RESULTS: It was established
      that 29.5% of patients under highly active antiretroviral therapy (ART) could be
      considered in TF. Among those, virological failure was most frequent (20.9%),
      followed by immunological- (14.0%) and clinical failure (4.7%). In patients
      showing lack of adherence to the treatment, the likelihood of suffering from TF
      and virogical failure were respectively increased by 6.67-fold and 12.19-fold,
      compared with patients showing good adherence. Although there was no
      statistically significant association, TF tended to be more frequent in young
      adults, in patients with low income and, low level of education. When ART
      regimens were compared, there was no apparent difference in TF between regimens
      based on non-nucleoside reverse transcriptase inhibitors and those based on
      protease inhibitors. This is very important in the context of recent ART
      strategies, such as early-initiated ART, aimed at achieving long-term infection
      control. CONCLUSIONS: Is confirmed the importance of treatment adherence to avoid
      TF and further highlights the importance of educating HIV-infected patients in
      all parts of the world, especially those individuals with a lower socio-economic
      status.

PMID- 25767305
TI  - The impact of foot arch height on quality of life in 6-12 year olds.
AB  - OBJECTIVE: To determine whether arch height has an effect on the health-related
      quality of life of schoolchildren. METHODS: One hundred and thirteen
      schoolchildren attended an out-patient centre where self-reported data were
      recorded, their feet were classified into one of three groups according to their
      arch index (high, normal or low) and the scores obtained from the Foot Health
      Status Questionnaire (FHSQ - Spanish version) were compared. RESULTS: The groups
      with high, low and normal arch recorded lower scores in Section One for the
      general foot health and footwear domains and higher scores in foot pain and foot
      function. In Section Two they obtained lower scores in general health and higher
      scores in physical activity, social capacity and vigour. CONCLUSIONS: Comparison
      of the scores obtained reveals that arch height has a negative impact on quality
      of life. Given the limited extent of available evidence in respect of the
      aetiology and treatment of foot diseases and deformities, these findings reveal
      the need to implement programmes to promote foot health and carry out further
      research into this commonly occurring disabling condition.

PMID- 25767306
TI  - Intra- and interobserver agreement on the Oestern and Tscherne classification of
      soft tissue injury in periarticular lower-limb closed fractures.
AB  - BACKGROUND: The soft tissues injury in periarticular fractures of the lower
      extremities determines the proper time to perform bone fixation. OBJECTIVE: The
      aim of this study was to determine the intra and interobserver agreement in the
      Tscherne classification. METHODS: This is a descriptive, prospective study for
      patients admitted to the Pablo Tobon Uribe Hospital (PTUH) with tibial plateau or
      tibial pilon fractures. We performed a standardize evaluation using video
      photography at the time of admission and 24, 48, and 72 h after admission.
      Fifteen five reviewers who had various levels of training produced a total of
      1,200 observations. The intra- and interobserver agreement was assessed using a
      weighted kappa for multiple raters and more than two categories. RESULTS: Twenty
      patients were admitted with tibial plateau and tibial pilon fractures. The
      intraobserver agreement for all 15 raters was kappa 0.81 (95% CI 0.79-0.83), and
      the interobserver agreement for all 15 raters was kappa 0.65 (95% CI 0.55-0.73).
      The interobserver agreement at 24 h was kappa 0.67 (95% CI 0.46-0.86).
      CONCLUSIONS: Classifying the severity of soft tissue injury is critical in
      planning the surgical management of fractures of the lower extremities. Based on
      our results, we can reasonably argue that the Tscherne classification produced an
      adequate level of agreement and could be used to standardize and to guide the
      treatment, and to conduct research studies.

PMID- 25767307
TI  - Elders Health Empowerment Scale: Spanish adaptation and psychometric analysis.
AB  - INTRODUCTION: Empowerment refers to patient skills that allow them to become
      primary decision-makers in control of daily self-management of health problems.
      As important the concept as it is, particularly for elders with chronic diseases,
      few available instruments have been validated for use with Spanish speaking
      people. OBJECTIVE: Translate and adapt the Health Empowerment Scale (HES) for a
      Spanish-speaking older adults sample and perform its psychometric validation.
      METHODS: The HES was adapted based on the Diabetes Empowerment Scale-Short Form.
      Where "diabetes" was mentioned in the original tool, it was replaced with
      "health" terms to cover all kinds of conditions that could affect health
      empowerment. Statistical and Psychometric Analyses were conducted on 648 urban
      dwelling seniors. RESULTS: The HES had an acceptable internal consistency with a
      Cronbach's alpha of 0.89. The convergent validity was supported by significant
      Pearson's Coefficient correlations between the HES total and item scores and the
      General Self Efficacy Scale (r= 0.77), Swedish Rheumatic Disease Empowerment
      Scale (r= 0.69) and Making Decisions Empowerment Scale (r= 0.70). Construct
      validity was evaluated using item analysis, half-split test and corrected item to
      total correlation coefficients; with good internal consistency (alpha> 0.8). The
      content validity was supported by Scale and Item Content Validity Index of 0.98
      and 1.0, respectively. CONCLUSIONS: HES had acceptable face validity and
      reliability coefficients; which added to its ease administration and users'
      unbiased comprehension, could set it as a suitable tool in evaluating elder's
      outpatient empowerment-based medical education programs.

PMID- 25767308
TI  - Histoplasmosis laryngeal: report first case in Colombia.
AB  - Laryngeal histoplasmosis is a fungal infection that is frequent in Colombia.
      Laryngeal histoplasmosis usually occurs in immunocompromised patients through the
      dissemination of the fungus from the lungs to other organs. Histoplasmosis
      isolated laryngeal (primary) is rare. If a patient presents with a history of
      immunosuppression by renal transplant, primary laryngeal histoplasmosis with
      supraglottic granulomatous inflammation that was treated with amphotericin B and
      Itraconazole, with complete resolution of laryngeal lesions. 

PMID- 25767311
TI  - Editor's Note.

PMID- 25767310
TI  - Quasi-Experimental Study of Functional Family Therapy Effectiveness for Juvenile
      Justice Aftercare in a Racially and Ethnically Diverse Community Sample.
AB  - Functional Family Therapy (FFT) is an intensive community-based treatment program
      designed to reduce youth behavior problems such as violence, drug use, and other
      delinquency. Although there is evidence of FFT efficacy and effectiveness with
      predominantly White samples, there is very little evidence with racial/ethnic
      minority samples. In light of the over-representation of African American and
      Latino youth in the juvenile justice system, this study examined the
      effectiveness of FFT and an adaptation of FFT to probation supervision, called
      Functional Family Probation (FFP), among a predominantly Latino and African
      American sample of youth returning home from court-ordered out-of-home placements
      (OHP). Propensity score weighting was used to compare the likelihood of
      subsequent OHPs among youth receiving standard probation (Comparison group), and
      youth receiving FFT (with standard probation), youth receiving FFP (instead of
      standard probation), and youth receiving FFT in combination with FFP. Results
      indicated that youth receiving FFT (both with standard probation and FFP),
      relative to Comparison youth receiving standard probation only, had significantly
      lower likelihood of OHP during the first two months following release, but this
      advantage disappeared in later months. Youth receiving only FFP also had lower
      likelihood of OHP than Comparison youth in the first two months, though not
      significantly. These findings provide encouraging evidence of positive effects of
      FFT, in combination with FFP or standard probation, among a diverse sample of
      juvenile justice system-involved youth.

PMID- 25767309
TI  - Fragile X syndrome.
AB  - Fragile X Syndrome (FXS) is a genetic disease due to a CGG trinucleotide
      expansion, named full mutation (greater than 200 CGG repeats), in the fragile X
      mental retardation 1 gene locus Xq27.3; which leads to an hypermethylated region
      in the gene promoter therefore silencing it and lowering the expression levels of
      the fragile X mental retardation 1, a protein involved in synaptic plasticity and
      maturation. Individuals with FXS present with intellectual disability, autism,
      hyperactivity, long face, large or prominent ears and macroorchidism at puberty
      and thereafter. Most of the young children with FXS will present with language
      delay, sensory hyper arousal and anxiety. Girls are less affected than boys, only
      25% have intellectual disability. Given the genomic features of the syndrome,
      there are patients with a number of triplet repeats between 55 and 200, known as
      premutation carriers. Most carriers have a normal IQ but some have developmental
      problems. The diagnosis of FXS has evolved from karyotype with special culture
      medium, to molecular techniques that are more sensitive and specific including
      PCR and Southern Blot. During the last decade, the advances in the knowledge of
      FXS, has led to the development of investigations on pharmaceutical management or
      targeted treatments for FXS. Minocycline and sertraline have shown efficacy in
      children. 

PMID- 25767312
TI  - Current scenario of spurious and substandard medicines in India: a systematic
      review.
AB  - Globally, every country is the victim of substandard or spurious drugs, which
      result in life threatening issues, financial loss of consumer and manufacturer
      and loss in trust on health system. The aim of this enumerative review was to
      probe the extent on poor quality drugs with their consequences on public health
      and the preventive measures taken by the Indian pharmaceutical regulatory system.
      Government and non-government studies, literature and news were gathered from
      journals and authentic websites. All data from 2000 to 2013 were compiled and
      interpreted to reveal the real story of poor quality drugs in India. For
      minimizing spurious/falsely-labelled/falsified/counterfeit drugs or not of
      standard quality drugs, there is urgent requirement of more stringent regulation
      and legal action against the problem. However, India has taken some preventive
      steps in the country to fight against the poor quality drugs for protecting and
      promoting the public health. 

PMID- 25767313
TI  - Myths and Facts about Vitiligo: An Epidemiological Study.
AB  - Vitiligo is a pigmentary disorder associated with many disease conditions that
      necessitates multiple drug regimens, which make the treatment complicated. This
      stigmatic disease forces the patient to approach all system of medicines as well
      as alternative medicines of non proven value, which further worsens the
      situation. At the same time the nonadherence to the treatment reflects poor
      prognosis, which is misunderstood for lack of response resulting in poor faith to
      the medications. The aim of this work was to assess the patient compliance and
      the factors affecting, and to monitor the adverse effects as well as drug
      interactions. The study was carried out in the Institute of Applied Dermatology
      for a period of one year. Patient compliance was assessed using Morisky
      Medication Adherence Scale and found that 71% of the patients were low adherent
      to medications. Family support, faith in doctor, higher educational status and
      effectiveness of the treatment were some of the reasons for medication adherence
      whereas forgetfulness, feasibility, occupational problem, polypharmacy, longer
      duration of treatment and the feeling that the disease under is control were some
      of the reasons listed for nonadherence. Three adverse reactions were reported
      with narrow band ultraviolet B and topical tacrolimus therapy and they were
      categorized into possible and probable according to causality assessment by
      Naranjo scale. Five drug interactions were reported and the causality assessment
      was done using drug interaction probability scale. None of the reactions were
      serious or life threatening. The present study revealed the hurdles in providing
      safe and effective treatment to the patients and also it suggest the need of
      doing more research on this disease since there is a general belief that vitiligo
      is an incurable disease. 

PMID- 25767314
TI  - Liquid Chromatographic Method for Irinotecan Estimation: Screening of P-gp
      Modulators.
AB  - The present work is aimed to develop a simple, sensitive, robust and reliable
      HPLC method for the estimation of irinotecan in the physiological media in order
      to assess the permeability profile of irinotecan, using the everted gut sac, in
      the presence of various P-gp modulators. Separation was achieved using, C18
      column with mobile phase consisting of acetonitrile and 0.045 uM sodium
      dihydrogen phosphate dihydrate buffer containing ion pair agent heptane sulphonic
      acid sodium salt (0.0054 uM), pH 3. The flow rate was maintained at 1 ml/min and
      analysis was performed at 254.9 nm using PDA detector. Calibration data showed an
      excellent linear relationship between peak-area verses drug concentration (r(2),
      0.9999). Linearity was found to be in the range of 0.060-10.0 ug/ml. Limits of
      detection and quantification were found to ~0.020 ug/ml and ~0.060 ug/ml,
      respectively. The developed method was found to be precise (RSD < 1.5%, for
      repeatability and <2.55% for intermediate precision, acceptable ranges of
      precision), accurate (The recovered content of irinotecan in the presence of
      various P-gp modulators varied from 96.11-101.51%, within acceptable range, 80
      120%), specific and robust (% RSD < 2). Developed method has been applied
      successfully for the evaluation of eleven P-gp modulators from diverse chemical
      class. 

PMID- 25767315
TI  - Novel 3,4-Methylenedioxybenzene Scaffold Incorporated 1,3,5-Trisubstituted-2
      pyrazolines: Synthesis, Characterization and Evaluation for Chemotherapeutic
      Activity.
AB  - A series of novel 3, 4-methylenedioxybenzene scaffold incorporated 1,3,5
      trisubstituted-2-pyrazoline derivatives was synthesised as potent antitubercular
      agents via chalcone intermediates by reaction with hydrazines. The structures of
      the compounds were confirmed by IR, 1HNMR, 13CNMR and mass spectral data. The
      novel pyrazolines were screened for in vitro antitubercular activity by almar
      blue dye method against M. tuberculosis H37Rv. All the compounds exhibited
      excellent activity that could be due to the presence of 3,4-methylenedioxybenzene
      frame work in the molecules. Some of the compounds also showed in vitro
      cytotoxicity on EAC cell lines in tryphan blue exclusion assay suggesting their
      safety. 

PMID- 25767316
TI  - Preparation and crystallographic analysis of gliclazide polymorphs.
AB  - Since the introduction of gliclazide in the pharmaceutical industry, a large
      number of research groups have been engaged in various investigations aiming to
      enhance its biomedical application. But, very limited efforts have been made to
      study polymorphism of gliclazide. Therefore, this study focuses on solvent
      induced polymorphism of gliclazide and its characterization by thermal methods.
      Three polymorphs namely, Form-I, II and III and an amorphous powder were produced
      from different solvents and solvent mixtures. Crystals were analyzed using
      infrared spectroscopy, differential scanning calorimetry, X-ray powder
      diffraction and single crystal x-ray diffraction. Polymorph Form-I is found to
      exist in centro-symmetric triclinic P-1 space group and has endothermic peak at
      162.93 degrees . Form-II has endothermic peak from 171.2 degrees  to 172.35
      degrees  and exists in centro-symmetric monoclinic P21/a space group while Form
      III has endothermic peak from 168.93 degrees  to 169.86 degrees  and exists in
      centro-symmetric monoclinic P21/n space group. The equilibrium solubility values
      of Form-I, II, III and the amorphous form were 0.4825+/-0.025, 0.2341+/-0.042,
      0.2581+/-0.038 and 0.5213+/-0.072 mg/ml, respectively. The Form-I has relatively
      higher solubility and similar to that of amorphous gliclazide. Form-II and Form
      III are relatively most stable and least soluble. However, there was no
      remarkable difference in their aqueous solubility under the conditions in which
      study was conducted. 

PMID- 25767317
TI  - In vitro Antioxidant Potential in Sequential Extracts of Curcuma caesia Roxb.
      Rhizomes.
AB  - Present study deals with antioxidant potential of sequential extracts of fresh
      and dried rhizomes of Curcuma caesia, using solvents viz., hexane, petroleum
      ether, benzene, chloroform, ethyl acetate, methanol and water, which was analyzed
      by 2,2-diphenyl-1-picrylhydrazyl radical scavenging assay, total antioxidant
      capacity, ferric reducing activity and thiobarbituric acid reactive species
      assay. Total phenol content was estimated by the Folin-Ciocalteau method. C.
      caesia showed significant antioxidant activity in chloroform, benzene and ethyl
      acetate extracts. The chloroform extract was highly effective as free radical
      scavengers, electron-donating agents and reducing molybdate ions except for
      reducing lipid peroxidation. The highest total phenol content was also exhibited
      by chloroform and benzene extracts. Antioxidant potential expressed by C. caesia
      in the sequential extracts could be effectively utilized for identification of
      the bioactive compounds for future phytopharmacological applications. 

PMID- 25767318
TI  - Matrix Solid-Phase Dispersion Extraction and Quantification of Alpinetin in
      Amomum Seed using Validated HPLC and HPTLC Methods.
AB  - Alpinetin is a flavonoidal constituent of seeds of Amomum subulatum Roxb.,
      recently reported to possess vasorelaxant and antiHIV activities. Simple,
      accurate and precise HPLC and HPTLC methods were developed for the analysis of
      alpinetin in A. subulatum seed extracts and extraction technique was optimized to
      get maximum yield using conventional, ultrasonic and matrix solid phase
      dispersion extraction. HPLC was performed on a C18 column with methanol and water
      (70:30, v/v) as mobile phase at a flow rate of 1.0 ml/min whereas HPTLC on silica
      aluminum sheet (60F254) using toluene, dichloromethane and ethyl acetate as
      solvent system. A sharp peak was obtained for alpinetin at a retention time (Rt)
      of 5.7 min by HPLC and retardation factor (Rf) of 0.48 by HPTLC. Both methods
      were validated as per the ICH guidelines and the content of alpinetin was
      estimated in different extracts. Matrix solid phase dispersion technique was
      found most suitable for extracting alpinetin as compared to other techniques.
      Validation data are indicative of good precision and accuracy and proved the
      reliability of the methods. 

PMID- 25767319
TI  - Bioadhesive films containing fluconazole for mucocutaneous candidiasis.
AB  - Fluconazole is a broad spectrum antifungal agent that has been extensively
      applied for the management of oral, pharyngeal and cutaneous candidiasis.
      Fluconazole has a high volume of distribution (0.55-0.65 l/kg) and has systemic
      toxicity due to high drug-drug interaction. The present study focuses on the
      formulation of bioadhesive film as a controlled release carrier for fluconazole.
      The formulation was intended to provide localized delivery of fluconazole
      exclusively at the site of infection, thereby reducing its total dose and hence,
      dose-related toxicities. Bioadhesive films were prepared by solvent casting
      method using sodium alginate and polyvinyl alcohol alone as well as in various
      combinations. Prepared films were evaluated for physical characteristics like,
      weight and content uniformity, film thickness, swelling index, microenvironment
      pH and folding endurance. In vitro drug release, in vitro and ex vivo residence
      time, bioadhesive strength and skin irritation were also studied. Accelerated
      stability study was conducted on the optimized formulation as per ICH guidelines.
      Weight of all the films were not more than 20 mg. Thickness of the films ranged
      between 0.09 to 0.15 mm whereas swelling indices showed a high extent of
      variation. Films composed of polyvinyl alcohol alone provided a swelling index of
      6%. Bioadhesive strength was found to be more than 18 g. Microenvironment pH was
      near to 7.0 for most of the formulations. Ex vivo residence time of optimized
      batch was more than 5 h and it provided controlled drug release up to 8 h. As
      revealed in FT-IR and DSC studies, drug was found to be compatible with the
      excipients used in this study. 

PMID- 25767320
TI  - Single and dual drug release patterns from shellac wax-lutrol matrix tablets
      fabricated with fusion and molding techniques.
AB  - The objective of this investigation was to prepare the shellac wax matrix tablets
      by fusion and molding technique incorporated with Lutrol in different ratios to
      modify the hydrophobicity of matrix tablet. The matrix tablets with single drug
      were loaded either with propranolol hydrochloride or hydrochlorothiazide as
      hydrophilic and hydrophobic model drugs, and a dual drug formula was also
      prepared. The single and dual drug release patterns were studied in a dissolution
      apparatus using distilled water as medium. Propranolol hydrochloride released
      from matrix was easier than hydrochlorothiazide. Drug release from shellac wax
      matrix could be enhanced by incorporation of Lutrol. However retardation of drug
      release from some matrix tablets was evident for the systems that could form
      dispersion in the dissolution medium. The gel network from high content of Lutrol
      was hexagonal which was a dense and more compact structure than the other
      structures found when low amounts of Lutrol were present in the formula.
      Therefore, the formulae with high content of Lutrol could prolong drug release
      more efficiently than those containing low content of Lutrol. Hence shellac wax
      matrix could modulate the drug release with the addition of Lutrol. Sustainable
      dual drug release was also obtained from these developed matrix tablets. Thus
      shellac wax-Lutrol component could be used as a potential matrix tablet prepared
      with fusion and molding technique with excellent controlled drug release. 

PMID- 25767321
TI  - Identification and Characterization of Hydrolytic Degradation Products of
      Cefditoren Pivoxil using LC and LC-MS/TOF.
AB  - The present research work was carried out to determine stability of cefditoren
      pivoxil, an orally absorbed prodrug that is rapidly hydrolysed by intestinal
      esterases to the active cephalosporin cefditoren. Cefditoren was subjected to
      stress conditions recommended by the International Conference on Harmonization of
      Technical Requirements for Registration of Pharmaceuticals for Human Use
      guideline Q1A (R2). Cefditoren pivoxil was susceptible for degradation under
      acidic, alkaline and neutral hydrolytic conditions while it was stable under
      photolytic and thermal stress conditions. Separation of cefditoren and
      degradation products were carried out by using HPLC. The unknown degradation
      products were characterized by liquid chromatography-mass spectrometry/time of
      flight studies. Structures were proposed for each fragment based on best possible
      molecular formula and complete degradation pathways were reported for cefditoren
      and its degradants. 

PMID- 25767322
TI  - Formulation and evaluation of mouth disintegrating tablets of atenolol and
      atorvastatin.
AB  - In this study, mouth-disintegrating tablets of atenolol and atorvastatin
      combination were formulated using superdisintegrants to impart fast
      disintegration. Fifteen formulations were prepared based on different
      concentrations of two superdisintegrants, croscarmellose sodium and Kyron-T134.
      Three different techniques such as direct compression, effervescent and
      sublimation were used to study the effect of manufacturing processes, nature and
      concentration of superdisintegrants on various features of these tablets. Five
      formulations were made using each method. Precompression studies like bulk
      density, tapped density, angle of repose, Carr's compressibility index, Hausner's
      ratio and compatibility studies such as Fourier transform infrared spectroscopy
      and differential scanning calorimetry were performed. Various features such as
      hardness, thickness, diameter, weight variation, friability, disintegration time,
      dissolution studies, wetting time, wetting volume, water absorption ratio,
      modified disintegration, uniformity of contents and stability were evaluated.
      Finally results were statistically analyzed by the application of one way ANOVA
      test. Formulation F13 containing Kyron-T134 (6%) and croscarmellose sodium (2%)
      was found to be the best among all fifteen formulations prepared in all aspects
      evaluated. Sublimation method is found to be the best among three methods of
      preparation used. 

PMID- 25767323
TI  - Separation and Identification of Phenolic Acid and Flavonoids from Nerium indicum
      Flowers.
AB  - Four major compounds were separated and identified from the methanol extracts of
      Nerium indicum flowers (Arali) using HPLC and mass spectral data. Through mass
      data, the chemical structures were elucidated as: trans5-O-caffeoylquinic acid
      (1), quercetin-3-O- rutinoside (2), luteolin-5-O-rutinoside (3) and luteolin-7-O
      rutinoside (4). In addition, the cis isomers of 5-O-caffeoylquinic acid in Nerium
      indicum flowers were confirmed by Mass, HPLC and UV. The structures of these
      compounds confirmed with the help of liquid chromatography mass spectrometry. 

PMID- 25767324
TI  - Protective effect of sitagliptin and rosuvastatin combination on vascular
      endothelial dysfunction in type-2 diabetes.
AB  - The present investigation aimed to evaluate the protective effects of
      sitagliptin, glimepiride, rosuvastatin and their combinations on oxidative stress
      and endothelial dysfunction in the aortic tissues in fructose-fed type-2 diabetic
      rats. Sitagliptin (20 mg/kg, p.o.), glimepiride (2 mg/kg, p.o.), rosuvastatin (5
      mg/kg, p.o.) and their combinations were administered for 6 w after induction of
      diabetes by fructose (66%, w/v solution, p.o. for 8 w) in wistar rats. The
      effects were examined on body weight, serum glucose, triglyceride, cholesterol,
      blood pressure, heart rate, nitric oxide and antioxidant defensive enzymes. After
      completion of treatment schedule, the blood pressure was determined by invasive
      method and vascular reactivity was tested with adrenaline, noradrenaline and
      phenylephrine. Endothelial dysfunction was determined by acetylcholine and sodium
      nitroprusside-induced vasorelaxation studies on isolated rat aortas. Long term
      treatments significantly decreased body weight gain, serum glucose, triglyceride
      and cholesterol levels; normalize the heart rate, and blood pressure in fructose
      fed rats. The treatments significantly improved vascular reactivity to
      catecholamines with reduction in elevated blood pressure in type-2 diabetic rats.
      The significant improvement in the relaxant response to acetylcholine and sodium
      nitroprusside was obtained on isolated aortas. All the treatments were effective
      in restoring defensive antioxidant enzymes. Sitagliptin and rosuvastatin were
      able to reverse endothelial dysfunction in type-2 diabetes, but better
      ameliorating potential was found when used in combination. 

PMID- 25767325
TI  - Effect of atracylodes rhizome polysaccharide in rats with adenine-induced chronic
      renal failure.
AB  - The aim of the study was to elucidate the therapeutic effects of Atracylodes
      rhizome polysaccharide on adenine-induced chronic renal failure in rats. Fifty
      male Sprague Dawley rats were selected and randomly divided in to 5 groups (n=10
      rats per group): The normal control group, the chronic renal failure pathological
      control group, the dexamethasone treatment group and two Atracylodes rhizome
      polysaccharide treatment groups, treated with two different concentrations of the
      polysaccharide, the Atracylodes rhizome polysaccharide high group and the
      Atracylodes rhizome polysaccharide low group. All the rats, except those in the
      normal control group were fed adenine-enriched diets, containing 10 g adenine per
      kg food for 3 weeks. After being fed with adenine, the dexamethasone treatment
      group, Atracylodes rhizome polysaccharide high group and Atracylodes rhizome
      polysaccharide low group rats were administered the drug orally for 2 weeks. On
      day 35, the kidney coefficient of the rats and the serum levels of creatinine,
      blood urea nitrogen, total protein and hemalbumin were determined. Subsequent to
      experimentation on a model of chronic renal failure in rats, the preparation was
      proven to be able to reduce serum levels of creatinine, blood urea nitrogen and
      hemalbumin levels (P<0.05) and improve renal function. Atracylodes rhizome
      polysaccharide had reversed the majority of the indices of chronic renal failure
      in rats. 

PMID- 25767326
TI  - Preparation and characterization of (125)i labeled bovine serum albumin.
AB  - Bovine serum albumin is a model protein, which has been conventionally used as
      protein standard and in many areas of biochemistry, pharmacology and medicine.
      Radioiodination procedure for bovine serum albumin employing chloramine-T as an
      oxidant with slight modification was evaluated critically to establish the
      optimal conditions for the preparation of radiolabeled tracer ((125)I-BSA) with
      required specific activity without impairing the immune reactivity and biological
      activity. Optimized radioiodination procedure involving 10 ug of chloramine-T
      along with 20 ug of sodium metabisulphite with 60 seconds incubation at 2 degrees
      yielded (125)I-BSA with high integrity. 

PMID- 25767327
TI  - TLC and HPTLC Fingerprints of Various Secondary Metabolites in the Stem of the
      Traditional Medicinal Climber, Solena amplexicaulis.
AB  - Aim of this study was to develop a TLC and a HPTLC fingerprint profiles for
      various secondary metabolites of methanol extracts of the stem of the traditional
      medicinal climber, Solena amplexicaulis. These studies were carried out as per
      the methods of Harborne and Wagner et al. The profiles of various individual
      secondary metabolites were made and developed for authentication. The methanol
      extract of the stem showed the presence of 6 alkaloids, 6 flavonoids, 2
      glycosides, 9 saponins and 3 terpenoids. Owing to the presence of rich variety of
      secondary metabolites, the stem extract of S. amplexicaulis is expected to
      exhibit therapeutic properties. 

PMID- 25767328
TI  - Microwave-assisted Extraction of Alantolactone and Isoalantolactone from Inula
      helenium.
AB  - Microwave-assisted extraction was used for the extraction of alantolactone and
      isoalantolactone from Inula helenium. Effects of various experimental factors
      including ethanol concentration, particle size, microwave radiation time, the
      ratio of material to liquid and extraction temperature on yield of alantolactone
      and isoalantolactone were evaluated. The optimal extracting process of the
      alantolactone and isoalantolactone from the root of the Inula helenium was 1 g
      plant sample (sifted through 140 mesh) mixed with 15 ml of 80% ethanol solution,
      microwave radiation 120 s at 50 degrees . Under these optimal conditions, the
      yield of alantolactone and isoalantolactone was 31.83+/-2.08 mg/g and 21.25+/
      1.37 mg/g, respectively. Compared with heat reflux extraction, ultrasound
      assisted extraction, microwave-assisted extraction was more efficient and
      timesaving for the extraction of alantolactone and isoalantolactone from Inula
      helenium. 

PMID- 25767329
TI  - Determination of ethanol content in ayurvedic formulations kumaryasava and
      mustakarista by gas chromatography.
AB  - In the present study, two brands of Kumaryasava and Mustakarista medicinally
      important ayurvedic preparations were studied for quality control parameters like
      physiochemical properties, ethanol content by specific gravity and gas
      chromatographic methods and the total phenolic content. Evaluation of
      physiochemical properties and total phenolic contents resulted in establishing
      ranges for routine analysis. In both the formulations, ethanol content observed
      by specific gravity method varied from 0.9 to 1.9% on day 0 and reduced on
      storage for 30 days ranging from 0.1-0.6% v/v. Similarly, ethanol content
      determined by GC on day 0 varied from 0.1-1.6% v/v and on 30th day from 0.011
      0.025% v/v. This reduction in ethanol content on storage might be due to loss
      caused by frequent opening of the container. 

PMID- 25767330
TI  - Age at Childbearing over Two Generations and Grandchildren's Cognitive
      Achievement.
AB  - We examine whether grandparents' and parents' ages at birth are associated with
      grandchildren's early cognitive achievement, and whether grandparents' or
      parents' socioeconomic status, health, and marital status mediate those
      associations. Our analysis is based on data from the Panel Study of Income
      Dynamics and its Child Development Supplement. A grandparent's age at the birth
      of their own children is robustly and positively associated with grandchildren's
      verbal achievement, but not with grandchildren's applied mathematics achievement,
      after controlling for parents' age at the grandchild's birth. The associations
      are similar in magnitude for grandmothers and grandfathers. A variety of
      indicators of social class in the grandparent and parent generations did not
      mediate this age effect. However, many of those indicators of grandparents'
      social class were directly or indirectly related to grandchildren's achievement.

PMID- 25767331
TI  - A New Augmentation Based Algorithm for Extracting Maximal Chordal Subgraphs.
AB  - A graph is chordal if every cycle of length greater than three contains an edge
      between non-adjacent vertices. Chordal graphs are of interest both theoretically,
      since they admit polynomial time solutions to a range of NP-hard graph problems,
      and practically, since they arise in many applications including sparse linear
      algebra, computer vision, and computational biology. A maximal chordal subgraph
      is a chordal subgraph that is not a proper subgraph of any other chordal
      subgraph. Existing algorithms for computing maximal chordal subgraphs depend on
      dynamically ordering the vertices, which is an inherently sequential process and
      therefore limits the algorithms' parallelizability. In this paper we explore
      techniques to develop a scalable parallel algorithm for extracting a maximal
      chordal subgraph. We demonstrate that an earlier attempt at developing a parallel
      algorithm may induce a non-optimal vertex ordering and is therefore not
      guaranteed to terminate with a maximal chordal subgraph. We then give a new
      algorithm that first computes and then repeatedly augments a spanning chordal
      subgraph. After proving that the algorithm terminates with a maximal chordal
      subgraph, we then demonstrate that this algorithm is more amenable to
      parallelization and that the parallel version also terminates with a maximal
      chordal subgraph. That said, the complexity of the new algorithm is higher than
      that of the previous parallel algorithm, although the earlier algorithm computes
      a chordal subgraph which is not guaranteed to be maximal. We experimented with
      our augmentation-based algorithm on both synthetic and real-world graphs. We
      provide scalability results and also explore the effect of different choices for
      the initial spanning chordal subgraph on both the running time and on the number
      of edges in the maximal chordal subgraph.

PMID- 25767332
TI  - Efficient Data Mining for Local Binary Pattern in Texture Image Analysis.
AB  - Local binary pattern (LBP) is a simple gray scale descriptor to characterize the
      local distribution of the grey levels in an image. Multi-resolution LBP and/or
      combinations of the LBPs have shown to be effective in texture image analysis.
      However, it is unclear what resolutions or combinations to choose for texture
      analysis. Examining all the possible cases is impractical and intractable due to
      the exponential growth in a feature space. This limits the accuracy and time- and
      space-efficiency of LBP. Here, we propose a data mining approach for LBP, which
      efficiently explores a high-dimensional feature space and finds a relatively
      smaller number of discriminative features. The features can be any combinations
      of LBPs. These may not be achievable with conventional approaches. Hence, our
      approach not only fully utilizes the capability of LBP but also maintains the low
      computational complexity. We incorporated three different descriptors (LBP, local
      contrast measure, and local directional derivative measure) with three spatial
      resolutions and evaluated our approach using two comprehensive texture databases.
      The results demonstrated the effectiveness and robustness of our approach to
      different experimental designs and texture images.

PMID- 25767333
TI  - ISU201 enhances the resolution of airway inflammation in a mouse model of an
      acute exacerbation of asthma.
AB  - Glucocorticoids are commonly used for treating asthma and its exacerbations but
      have well-recognised adverse effects and are not always effective. Few
      alternative treatments exist. Using a murine model of an acute exacerbation of
      asthma, we assessed the ability of ISU201, a novel protein drug, to suppress the
      inflammatory response when administered after induction of an exacerbation.
      Sensitised mice were chronically challenged with a low mass concentration of
      aerosolised ovalbumin, and then received a single moderate-level challenge to
      simulate an allergen-induced exacerbation. ISU201 was administered to mice 2 and
      8 hours later, while pulmonary inflammation and expression of mRNA for chemokines
      and proinflammatory cytokines were assessed after 4, 12, and 24 hours. Relative
      to vehicle-treated controls, ISU201 suppressed accumulation of pulmonary
      neutrophils and eosinophils, while accelerating the decline in CXCL1, TNF-alpha,
      and IL-6 in lavage fluid and lung tissue. ISU201 significantly reduced peak
      expression of mRNA for the chemokines Cxcl9 and Cxcl10, the adhesion molecules
      Icam1 and Vcam1, and the proinflammatory cytokines Il1b, Il12p40, and Csf1. The
      ability of ISU201 to promote resolution of inflammation suggests that it may have
      potential as an alternative to glucocorticoids in the management of asthma,
      including when administered after the onset of an acute exacerbation. 

PMID- 25767334
TI  - The olive oil-based lipid clinoleic blocks leukocyte recruitment and improves
      survival during systemic inflammation: a comparative in vivo study of different
      parenteral lipid emulsions.
AB  - Although fish oil-based and olive oil-based lipid emulsions have been shown to
      exert anti-inflammatory functions, the immunomodulating properties of lipids are
      still controversial. Therefore, we investigated the anti-inflammatory effect of
      three different parenterally administered lipid emulsions in vivo: olive oil
      based Clinoleic, fish oil-based Smoflipid, and soybean oil-based Lipofundin. We
      observed leukocyte recruitment in inflamed murine cremaster muscle using
      intravital microscopy and survival in a murine model of LPS-induced systemic
      inflammation and analyzed expression of leukocyte and endothelial adhesion
      molecules. Olive oil-based Clinoleic and fish oil-based Smoflipid profoundly
      inhibited leukocyte adhesion compared to Lipofundin during LPS-induced
      inflammation of the murine cremaster muscle. In the trauma model of cremaster
      muscle inflammation, Lipofundin was the only lipid emulsion that even augmented
      leukocyte adhesion. In contrast to Smoflipid and Lipofundin, Clinoleic
      effectively blocked leukocyte recruitment and increased survival during lethal
      endotoxemia. Flow chamber experiments and analysis of adhesion molecule
      expression suggest that both endothelial and leukocyte driven mechanisms might
      contribute to anti-inflammatory effects of Clinoleic. We conclude that the anti
      inflammatory properties of Clinoleic are superior to those of Smoflipid and
      Lipofundin even during systemic inflammation. Thus, these results should
      stimulate further studies investigating parenteral lipids as an anti-inflammatory
      strategy in critically ill patients. 

PMID- 25767335
TI  - Oral hybrid verrucous carcinoma: a clinical study.
AB  - Hybrid Verrucous Carcinoma is an uncommon tumour wherein Verrucous Carcinoma (VC)
      is coexisting with conventional Squamous Cell Carcinoma (SCC) within same
      maternal field. The heterogeneous nature, infrequency of occurrence and the
      difficulties associated with diagnosis and management of this tumor is discussed
      through a retrospective study. Patients of primary hybrid VC treated from Jan
      2010 to May 2013 at a tertiary institute were analyzed on multivariate cox
      regression model. During the above mentioned period; 37 patients of hybrid VC
      were reported; 18(48.6 %) were male and 19(51.3 %) were female. Age ranged
      between 33 years to 78 years. Median follow up period was 32 months. T stage
      status and Stage grouping was not statistically significant for mortality (p
      value: 0.338). In the multivariate cox-regression model, the presence of second
      primary oral cancer was significantly associated with mortality, adjusted HR;
      23.10 (95 % CI: 1.73, 307.65) (p = 0.017). Tumour staging is often unreliable in
      predicting prognosis of hybrid VC, occurrence of second primary oral cancer and
      recurrence appears to be significant factors effecting prognosis. 

PMID- 25767336
TI  - Dr. Thomas cherian; father of cancer surgery in kerala.
AB  - Dr. Thomas Cherian (1940-2014) is one of the first surgical oncologists from
      State of Kerala, India. A humble human being, dexterous surgeon, untiring worker,
      and a dynamic personality that was Dr. Thomas Cherian. His vision, hardworking
      abilities and indomitable spirit were exemplary. He has paved path for the
      development of surgical oncology in Kerala. This article portrays not only the
      life of a selfless man, but also the beginning of a new speciality of Surgical
      Oncology in Kerala. 

PMID- 25767337
TI  - Factors affecting health related quality of life of rectal cancer patients
      undergoing surgery.
AB  - Maintaining quality of life (QOL) is one of the important aims of cancer
      treatment. Quality of life of a cancer patient is affected by various factors,
      which may be disease related, patient related, or treatment related. To study
      changes in health-related quality of life (HRQOL) brought about by treatment of
      rectal cancer and factors affecting the changes using Malayalam translation of
      FACT-C (Functional Assessment of Cancer Therapy-Colorectal) Questionnaire. Also
      to detect the minimally important clinical changes (MICC) in health-related
      quality of life of patients with carcinoma rectum, who have undergone surgery.
      Forty-five patients diagnosed with carcinoma rectum, who have undergone curative
      surgery, were studied. HRQOL was assessed at baseline 2 weeks after surgery and 3
      months after surgery. The changes in scores were correlated with various
      demographic factors like age, sex, marital status, number of children, number of
      married children, and education and occupation of the patient and spouse. Also
      the treatment-related factors like presence of stoma, presence of morbidity,
      previous treatment, stage of disease, and administration of chemotherapy before
      and after surgery were correlated. All the subscales of FACT-C tool, except
      emotional well-being, were significantly reduced 2 weeks after surgery and
      increased slightly above pre-treatment level 3 months after surgery. The
      Chronbach alpha values were 0.88, 0.89 and 0.86 on three occasions, respectively,
      establishing internal validity of the test. Baseline HRQOL scores were better in
      males compared to females. Among the various subscales, the drops in SWB, FWB,
      FACT-G, total Score and TOI were significant (P < .05).There were no significant
      differences in scores between patients who have undergone open surgery and
      minimally invasive surgery or patients who had permanent colostomy versus no
      colostomy. The HRQOL scores after surgery reduced 2 weeks after surgery and
      improved above pre-surgical levels 3 months after surgery. The approach of
      surgery (minimally invasive versus open) or presence or absence of permanent
      colostomy didn't make any significant change in HRQOL. But since the sample size
      of the study was small, we need further larger studies to arrive at definite
      conclusions. 

PMID- 25767339
TI  - Tuberculous celiac axis lymphadenopathy mimicking cystic pancreatic neoplasm - a
      diagnostic dilemma.
AB  - Cystic pancreatic neoplasms are tumors with malignant potential treated
      surgically. Isolated tuberculosis of celiac lymph nodes is rare, treatment of
      this entity being non-surgical. Radiological appearances of cystic pancreatic
      neoplasm and tuberculous peripancreatic lymph nodal mass is similar and difficult
      to differentiate. Here we present a case of mass lesion in the region of
      pancreatic head mimicking cystic pancreatic neoplasm which was actually abdominal
      tuberculous lymphadenopathy proven by biopsy. 

PMID- 25767338
TI  - "Peripherally inserted central catheters: our experience from a cancer research
      centre".
AB  - Peripherally inserted central catheter (PICC) is a modern drug delivery system
      utilised in oncology practice. The purpose of this study was to determine the
      complications associated with PICCs within a one year study period. PICCs
      inserted in patients registered at Dharamshila Cancer Hospital and research
      centre from 1st July 2012 to 30th June 2013 were studied. Data was retrieved from
      the procedure room records, medical records department, department of radiology
      and department of microbiology. Data was collected by oncology residents and
      procedure team. A total of 246 PICCs were inserted during the one year period.
      Complete data was not available in 23 patients. 223 results were included in the
      final analysis. USG guidance was required in 14 patients (6.3%). Optimal PICC
      duration was achieved in 151 patients (67.7%). 28 patient developed culture
      positive infective complications (12.5%). 44 patients developed mechanical
      complications (19.7%). Our study shows a relatively higher rate of infective
      complications. PICC is an acceptable means of drug delivery system. 

PMID- 25767340
TI  - Can molecular subtyping replace axillary nodal status as prognostic marker in
      breast cancer?
AB  - Subtypes are an established prognostic factor of BC in western population but its
      significance in Indian BC patients has not been evaluated. Thus this study
      provides an insight into the prognostic significance of molecular classification
      and its effect on the survival of BC patients in Eastern India. In this hospital
      based study 242 BC patients attending a Comprehensive Breast Service Clinic of a
      reputed institute in Eastern India and having IDC were studied over a period of 7
      years (January 2007 to October 2013). Nonluminal HER-2-positive and Triple
      negative tumors were associated with advanced stage of disease, metastatic lymph
      nodes and NPI >=5.4, whereas Luminal 1 and Luminal 2 tumors were associated with
      early stage, uninvolved lymph nodes and NPI <5.4. Better survival was observed
      for the patients with Luminal 1 [OS = 57.1 % (n = 36)] and Luminal 2 [OS = 60.0 %
      (n = 6)], compared to Triple negative [OS = 33.6 % (n = 38)] and nonluminal HER-2
      positive tumors [OS = 32.1 % (n = 18)]. This study provided some idea about the
      pattern of BC on the basis of classification by molecular profiling. Our study
      indicated that Triple negative and nonluminal HER-2-positive tumors have reduced
      DFS and OS compared with luminal 1 and 2 subtypes. In our patients, Triple
      negative and nonluminal HER-2-positive tumors were associated with established
      unfavorable prognostic indicators and this reflects the data in the western
      literature. The results suggest that the molecular subtypes are an independent
      prognostic and predictive marker in Indian BC patients. Whether or not molecular
      subtyping of breast cancer can replace axillary lymph nodes as the standard in
      prognosis remains to be seen, but if molecular subtyping can provide more
      information than the axilla about the prognosis and treatment option, it may well
      be the future of prognostication. 

PMID- 25767341
TI  - Follicular Dendritic Cell Sarcoma Mediastinum - a case report.
AB  - Follicular dendritic cell tumor (FDCT) are extremely rare difficult to diagnose
      category tumors.There has been a considerable controversy in medical community
      regarding precise classification and optimal management of this tumor with some
      treating it as a form of non Hodgkins lymphoma and some as soft tissue
      sarcomas.The number of published cases are still low and documentation too
      heterogenous to give statistically ified therapeutic recommendation of these
      tumors.This case report aims to highlight various aspects of diagnosing and
      treating this rare entity. 

PMID- 25767342
TI  - Cervical chondrosarcoma- rare malignancy: a case report.
AB  - To highlight an uncommon bone malignancy, which presented to our institute, as a
      neck swelling in the supraclavicular region. A 30 year old man presented with
      history of swelling on the left side of neck since 1 year and numbness of left
      upper limb since 6 months. Magnetic Resonance Imaging of the Cervical spine & MR
      Angiography showed a 7.4 * 4.6 cm expansile lesion involving transverse process
      of C5-C7 vertebrae. As the tumour was found to be deep to the phrenic nerve &
      brachial plexus, a dual approach was used, anteriorly via neck incision and
      posteriorly via the spine. The tumour was resected & iliac crest grafted along
      with stabilization of the cervical spine. Patient is disease free and the
      cervical spine stabilized with normal movements at two and half years follow up.
      We need to consider tumour arising from the vertebra as a differential diagnosis
      for any deep seated hard neck swelling in the supraclavicular region. Even low
      grade malignancy of this region when resected en-bloc will have a good prognosis.

PMID- 25767343
TI  - Congenital infantile fibrosarcoma of scalp. Is adjuvant therapy essential ?
AB  - Congenital infantile fibrosarcoma (IFS) is a rare tumour. Involvement of scalp is
      extremely rare and only a few case reports have been published till now. The
      exact management of these tumours is controversial. Their counterparts which
      involve the limbs more commonly can be radically excised, however this option is
      not possible in scalp. Adjuvant radiotherapy and chemotherapy has been advocated
      in such cases. Local recurrences and distant metastasis have been reported
      inspite of such therapy. We report a rare case of scalp IFS which was present
      since birth and was managed by surgical excision without radio and chemotherapy.
      Patient is well after 10 years of follow up. 

PMID- 25767344
TI  - Rare gigantic giant cell tumor of anterior ribs in a young lady.
AB  - Any mass arising from the breast region need not to be breast carcinoma! A
      rapidly growing mass from the chest wall need not to be highly malignant! The
      present case report defines the thin line between the two extremes and high
      lightens the importance of a good clinical examination followed by a judicial
      management. The lady in question had a huge Giant cell tumor in the Anterior arc
      of ribs which is quite rare, making it the second largest tumor been reported so
      far and the largest in Asia. The patient was referred to us by the Department of
      Thoracic Surgery in view of the aggressive nature of the lesion and the
      requirement of a major reconstructive surgery for the chest wall. The
      reconstructive procedure chosen was time tested and not new yet not so popular in
      the present time. It could cover such a huge chest wall defect with minimum
      morbidity and good results. 

PMID- 25767345
TI  - Metachronous metastasis to the oral cavity from carcinoma rectum - a case report
      and review of literature.
AB  - The common patterns of dissemination and recurrence of rectal cancer are known
      and well documented. However extravisceral involvement is a relatively uncommon
      entity. Therefore, these metastases are not well studied in sufficiently large
      numbers to formulate evidence based recommendations regarding their optimal
      treatment. This report describes a case of carcinoma of the rectum metastatic to
      the oral cavity causing symptoms severe enough to necessitate operative
      management. 

PMID- 25767346
TI  - "Difficult to flush chemoport: an important clinical sign".
AB  - A central venous access device is an intravenous device whose internal tip lies
      in a large central vein. Chemoport is a central venous device which serves
      various purposes in oncology practice apart from optimum delivery of
      chemotherapy. Various early and late complications have been frequently reported
      with the use of these devices. Fracture-embolization of the port catheter is an
      uncommon but life-threatening complication. Timely recognition and management is
      important to minimize the morbidity and mortality. 

PMID- 25767347
TI  - Unusual late complication following anterior pelvic exenteration and ileal
      conduit.
AB  - We report an unusual case of Conduit Perineal Fistula following Anterior Pelvic
      Exenteration and Ileal conduit, performed for cancer cervix in a patient who had
      post radiotherapy residual disease. Revision surgery and redo conduit with
      transverse colon was done. Patient tolerated the procedure well and postoperative
      period was uneventful. Patient was subsequently disease free for 27 months. She
      developed a pelvic recurrence and lived with the disease for another 36 months
      and was then lost to follow up. 

PMID- 25767348
TI  - Spindle cell sarcoma of thyroid: a case report.
AB  - Spindle cell sarcoma of thyroid represents a rare entity that may arise primarily
      from thyroid gland as a variant of thyroid cancer or as metastatic. We report a
      case of 60 year old man who presented with 2 months history of rapidly growing
      thyroid enlargement with no obstructive features and preliminary diagnosis of
      spindle cell lesion of thyroid was made with cytological examination. He
      underwent total thyroidectomy and histological examination revealed spindle cell
      sarcoma of thyroid confirmed by immunohistochemical reactions. He was subjected
      to adjuvant chemoradiotherapy and is on follow up. Sarcoma of thyroid is rarely
      encountered in routine practice and is diagnosed by microscopic evaluation and
      immunohistochemical staining which determines the cellular origin and histologic
      type of tumor . Sarcoma thyroid is best managed with surgery and adjuvant
      chemoradiotherapy according to the grade of the lesion. In addition overall
      prognosis in thyroid sarcoma is poor due to late presentation and aggressive
      nature of the tumour. 

PMID- 25767349
TI  - Rehabilitation of post surgical maxillectomy defects using interim obturators-a
      case series.
AB  - Prosthetic rehabilitation of extensive maxillectomy defects are exigent given the
      difficulties faced due to loss of palatal bone,teeth and surrounding supporting
      tissues which help in retention, support and stability of the prosthesis. An
      interim maxillary obturator is a prosthesis which is made after surgical
      resection of a portion or all of one or both maxilla where initial healing is
      completed. Frequently many or all teeth in the defect area are replaced by this
      prosthesis. It plays a vital role in preventing the facial disfigurement and
      irritation to the surgical site thereby enhancing the healing and restores the
      functional capabilities such as speech, mastication, deglutition etc. To gain
      better retention and stability, preservation of the unaffected regions is needed
      which can be achieved by proper surgical planning and designing of the
      prosthesis. This case series describes rehabilitation of three extensive
      maxillectomy defects with hollow open and closed interim obturators. 

PMID- 25767350
TI  - Papillary thyroid carcinoma in a 5-year-old child-case report.

PMID- 25767351
TI  - Spontaneous chemoport fracture and cardiac migration.
AB  - Central venous access devices are routinely used in oncology for delivering
      chemotherapy of which implantable chemoports are the most common. Spontaneous
      breakage and migration of the catheters is a very rare but known complication of
      the procedure. Patients will usually present with cardiac manifestations in form
      of chest pain or arrythmias. Herein we report a case of spontaneous breakage and
      cardiac migration in which the patient was asymptomatic. Patient was successfully
      managed by an interventional cardiologist. 

PMID- 25767352
TI  - H1N1: The dental perspective.

PMID- 25767353
TI  - Myeloperoxidase level around dental implants as an indicator of an inflammatory
      process.
AB  - AIM: Myeloperoxidase (MPO) has been widely used as an inflammatory marker of both
      acute and chronic conditions. The aim of the present study was to analyze MPO
      found in the peri-implant sulcus fluid of implants (PISF) and gingival cervicular
      fluid (GCF) of natural teeth in healthy or diseased states. MATERIAL AND METHODS:
      A total of 107 dental implant sites, either healthy/noninflamed, inflamed or
      affected by periodontitis, were classified and GCF/PISF samples were obtained.
      GCF/PISF MPO was spectrophotometrically determined. RESULTS: Both the GCF and the
      PISF volumes exhibited a gradual increase with gingival inflammation (P < 0.05).
      PISF from inflamed sites (P = 0.0001) and GCF from the gingivitis and
      periodontitis sites showed significantly higher total MPO levels (P < 0.05) in
      comparison with the noninflamed sites. The volumetric similarities of PISF and
      GCF in terms of response to inflammation were seen in the present study. However,
      some differences in PISF and GCF were observed. CONCLUSION: PISF may be suggested
      to have a considerable diagnostic potential as it exhibits the biologic changes
      around load-bearing endosseous dental implants.

PMID- 25767354
TI  - To determine and compare the position of neutral zone in relation to crest of
      mandibular alveolar ridge with different duration of edentulousness: A clinico
      radiographic study.
AB  - PURPOSE: The purpose of this study was to establish a relation between the crest
      of alveolar ridge and functionally obtained neutral zone and to determine the
      effect of duration of edentulousness on the location of neutral zone in relation
      to the crest of residual alveolar ridge. MATERIALS AND METHODS: The study
      included three groups: Group I-15 subjects edentulous for 0 months to 2 years;
      Group 2-15 subjects edentulous for 2-5 years; and Group 3-15 subjects edentulous
      for more than 5 years. Neutral zone recording was performed for each subject and
      the buccolingual relationship of the crest of the mandibular alveolar ridge and
      position of the neutral zone was examined. The results were analyzed by the
      Kruskal-Wallis H test and the Chi-square test. RESULTS: The results suggested
      that the location of the neutral zone varies from individual to individual
      depending on their musculature and that there is a significant relation to the
      duration of edentulousness. As edentulousness increases, there is more lingual
      positioning of the neutral zone at the molar region of both sides of the arch. At
      the premolar region, there is no change in position of the neutral zone; it
      remains constant as resorption of the alveolar ridge is directly under the
      buttress. In the anterior region, there is more labial positioning of the neutral
      zone as edentulousness increases. CONCLUSIONS: This technique proves itself to be
      an easy and inexpensive way to determine the relationship between the crest of
      alveolar ridge and neutral zone. Incorporating this technique into practice will
      be a great aid that can be exploited by the clinicians for functional and
      psychological comfort of the patients.

PMID- 25767355
TI  - Relative efficacy of pimecrolimus cream and triamcinolone acetonide paste in the
      treatment of symptomatic oral lichen planus.
AB  - BACKGROUND AND OBJECTIVES: Oral lichen planus (OLP) is a relatively common,
      chronic inflammatory condition that frequently presents with symptoms of pain and
      burning sensation. It is generally a very unrelenting disorder despite several
      kinds of treatment. Only symptomatic OLP requires treatment, and it remains a
      challenging predicament. Efforts are made in a sustained manner for searching for
      novel therapies for symptomatic OLP. Therefore, this study was aimed to compare
      the efficacy of treatment with topical pimecrolimus cream 1% with that of
      triamcinolone acetonide oral paste 0.1% in subjects with symptomatic OLP.
      MATERIALS AND METHODS: A prospective, parallel-group, randomized, active control
      clinical study was conducted among 30 symptomatic OLP subjects (20 females and 10
      males, with 15 patients in each treatment group) treated with topical
      pimecrolimus 1% cream and triamcinolone acetonide 0.1% oral paste four times
      daily for two consecutive months and treatment-free follow-up was performed for 2
      months. Pain or burning sensation, mean clinical score and presence of
      erythematous areas were assessed. The data obtained were statistically analyzed
      using Wilcoxon's Rank test and the Mann Whitney test. RESULTS: Subjects in both
      the groups showed significant improvement in symptom scores; however, the overall
      treatment response was higher in the pimecrolimus group compared with the
      triamcinolone acetonide group. On intergroup comparison, there was no
      statistically significant difference between the groups in the reduction in
      burning sensation (P = 0.18) and erythematous area (P = 0.07), but there was a
      statistically highly significant improvement in reduction of clinical scoring (P
      < 0.01%). Following the termination of the treatment, sustained remission of
      symptoms and long-lasting therapeutic effects was detected in 93.3% of the
      patients treated with pimecrolimus. INTERPRETATION AND CONCLUSION: Topical
      pimecrolimus 1% cream showed better therapeutic response compared with
      triamcinolone acetonide 0.1% oral paste in subjects with symptomatic OLP.

PMID- 25767356
TI  - Comparison of Periochip (chlorhexidine gluconate 2.5 mg) and Arestin (Minocycline
      hydrochloride 1 mg) in the management of chronic periodontitis.
AB  - BACKGROUND: The aim of the study was to compare the efficacy of chlorhexidine
      gluconate 2.5 mg (Periochip) and Minocycline hydrochloride 1 mg (Arestin) as
      local drug delivery agents in the management of chronic periodontitis. MATERIALS
      AND METHODS: Twenty patients in the age group of 30-50 years suffering from
      chronic periodontitis (12 males and 8 females), with almost identical probing
      depth bilaterally (5-8 mm), and exhibiting bleeding on probing were selected and
      divided into two groups: Group I consisted of periodontal pockets on the left
      side and received Periochip and group II consisted of periodontal pockets on the
      right side and received Arestin. Patients were recalled after 6 weeks and 3
      months intervals from the baseline visit to record plaque index, gingival index,
      and probing depth. RESULTS: There was reduction in all the parameters in both the
      groups at 6 weeks and 3 months as compared to baseline. CONCLUSION: From the
      results of the present study, it was concluded that both the drugs were equally
      effective in reduction of plaque scores as well as gingival scores. It was
      further observed that Arestin resulted in better results at 6 weeks while
      Periochip showed better results at 3 months with respect to probing depth
      reduction.

PMID- 25767357
TI  - Prevalence of Taurodont molars in a North Indian population.
AB  - BACKGROUND: It is very important for dentists to be familiar with anomalies of
      teeth not only for the clinical complications but also their management.
      Taurodontism also provides a valuable clue in detecting its association with
      various syndromes and other systemic conditions. The purpose of this study was to
      assess the prevalence of Taurodont molars among a North Indian population.
      MATERIALS AND METHODS: A total of 1000 patients' full-mouth periapical
      radiographs were screened. The radiographs were evaluated under optimal
      conditions using double magnifying glasses. A total of 7615 molars (including
      third molars) were evaluated. The relative incidence and the correlations
      regarding the location of Taurodont teeth (right versus left side and maxillary
      versus mandibular) were analyzed using the Chi-square test. RESULTS: Twenty-eight
      patients were found to have a Taurodont molar (11 women and 17 men [P = 0.250]).
      The prevalence of Taurodont molar was 2.8%. Males had a higher prevalence rate
      than females (3.4% vs. 2.2%, respectively). A cluster analysis of total
      Taurodonts in the mandible (45%) versus maxilla (55%) of both males and females
      combined showed a statistically significant difference (P < 0.05). CONCLUSION:
      The occurrence of Taurodontism is basically based on racial expression in
      different populations. These variations in prevalence between different
      populations may be due to ethnic variations. The occurrence of Taurodont molars
      among this Indian population was rare.

PMID- 25767358
TI  - Prevalence of psychiatric co-morbidity among patients attending dental OPD and
      the role of consultation-liaison psychiatry in dental practice in a tertiary care
      general hospital.
AB  - BACKGROUND: Psychiatric co-morbidities are frequent among patients attending
      dental OPD, some of which go unrecognized and hence untreated. AIMS: The present
      study has been carried out to detect the psychiatric co-morbidities among dental
      patients and determine the scope of consultation-liaison (C-L) psychiatry in a
      rural teaching hospital regarding comprehensive management of the patients.
      SETTINGS AND DESIGN: This cross-sectional, descriptive type study was conducted
      in a multi-speciality tertiary care teaching hospital in the northern part of
      West Bengal, India. MATERIALS AND METHODS: One hundred patients attending the
      dental OPD were randomly included in the study and every patient was
      consecutively referred to psychiatry department for assessment, during the period
      from 1(st) November 2013 to 30(th) April 2014. All referred patients were
      clinically examined and psychiatric co-morbidity was assessed by the help of
      General Health Questionnaire (GHQ)-28 and Mental Status Examination. STATISTICAL
      ANALYSIS USED: The data were subjected to statistical package for social sciences
      (SPSS), version 16, and statistically analyzed using Cross tab and Chi test. P
      <0.05 was considered to be statistically significant. RESULTS: The commonest
      dental illness was dental caries (22%). More than two-third of the patients had
      psychiatric co-morbidity according to GHQ-28 total score. Sixty-eight patients
      were diagnosed to have mental disorder on mental status examination. Somatoform
      disorder (25%) was the commonest type of mental disorder, followed by mixed
      anxiety and depression (14%). CONCLUSIONS: This study has pointed the need for
      psychological examination of patients visiting dental specialty with unexplained
      physical symptoms. Such patients can be identified and treated, provided a
      psychiatric consultation service exists.

PMID- 25767359
TI  - Role of bacteria in oral carcinogenesis.
AB  - Oral cancer appears to be increasing in incidence, and mortality has hardly
      improved over the past 25 years. Better understanding of the etiopathogenesis
      should lead to more accurate and earlier diagnosis and more effective treatments
      with fewer adverse effects. Despite increasing interest in the possible
      relationships between bacteria and the different stages of cancer development,
      the association of bacteria with cancer of the oral cavity has yet to be
      adequately examined. Different bacteria have been proposed to induce
      carcinogenesis, either through induction of chronic inflammation or by
      interference, either directly or indirectly, with eukaryotic cell cycle and
      signaling pathways or by metabolism of potentially carcinogenic substances like
      acetaldehyde, causing mutagenesis. This review presents the possible
      carcinogenesis pathway involved in bacterial carcinogenesis, commonly implicated
      bacteria in oral carcinogenesis and their role in cancer therapeutics as well. 

PMID- 25767360
TI  - Accessory mental foramina, incisive nerve plexus and lingual canals with unusual
      emergence paths: Report of two rare cases.
AB  - Being knowledgeable of neurovascularization of anterior mandible is crucial for
      successful local anesthesia and for safe minor and major oral surgeries of this
      part. The first case was 62 years old and was found to have two accessory mental
      foramina with buccal emergence on the left side and two accessory mental foramina
      with buccal and lingual emergence paths on the right side (overall five mental
      foramina). Incisive nerve plexus with multiple cephalic branching was obvious on
      both sides. The second case was 60 years of age and had two lingual foramina on
      the lingual side with two accessory foramina on the buccal side of the symphysis.
      Considering our findings, a pre-operation limited cone beam computed tomography
      is suggested to avoid inadvertent damage, especially when planning a surgery in
      the mandibular inter-mental region. 

PMID- 25767361
TI  - Solitary lipoma in the retromandibular region.
AB  - Lipomas are the most common subcutaneous soft-tissue tumors. These are benign
      tumors originating from the adipocytes. They may be located in any part of the
      body and can be confused clinically with other soft tissue masses. They
      infrequently occur in the head and neck region. We present a case of solitary
      lipoma arising in the neck region that was reported to our division of oral and
      maxillofacial surgery. 

PMID- 25767362
TI  - Malignant peripheral nerve sheath tumor: A rarity.
AB  - Malignant peripheral nerve sheath tumor (MPNST) of the mandible is an uncommon
      tumor that develops either from a preexisting neurofibroma or de novo. MPNSTs are
      sarcomas that originate from peripheral nerves or from cells associated with the
      nerve sheath, such as Schwann cells, perineural cells or from fibroblasts.
      Because MPNSTs can arise from multiple cell types, the overall appearance can
      vary greatly from one case to the next. A case of MPNST of the right side of the
      mandible in a 23-year-old female is reported. 

PMID- 25767363
TI  - Off-label drug use in Psychiatry Outpatient Department: A prospective study at a
      Tertiary Care Teaching Hospital.
AB  - INTRODUCTION: Off-label drug prescribing is very common in Psychiatry. US-Food
      and Drug Administration has defined off-label drug as "use of drugs for the
      indication, dosage form, regimen, patient or other use constraint not mentioned
      in the approved labeling." OBJECTIVE: The objective was to evaluate off-label
      drug use in patients attending Outpatient Department of Psychiatry. MATERIALS AND
      METHODS: One year prospective, cross sectional study was conducted on patients
      attending Psychiatry Outpatient Department. Demographic data, clinical history,
      and complete prescription were noted in the predesigned proforma and
      prescriptions were analyzed for off-label drug use as per British National
      Formulary-2011. RESULT: A total of 250 patients were enrolled with mean age 40.36
      +/- 12.3 years. Most common diagnosis was major depressive disorder 101 (40.4%).
      A total of 980 drugs (mean 3.68 +/- 1.42) were prescribed out of which 387
      (39.5%) were off-label. Of 250 patients, 198 (79.2%) received at least one off
      label drug. Psychopharmacological agents most frequently used in off-label manner
      were clonazepam 31 (12.4%), lorazepam 30 (12%), and trihexyphenidyl HCl 25 (10%).
      Prevalence of off-label use of these three drugs was significantly higher than
      other off-label drugs (P < 0.0001, P < 0.0001 and P < 0.0001 respectively).
      Inappropriate indication was the most common category of off-label use. There was
      positive and significant correlation between off-label prescribing and number of
      drugs (r = 0.722, P <= 0.000). Off-label prescribing was statistically
      significantly higher in 21-40 year age group, but no difference was seen in any
      co-morbid condition or in between any psychiatric disorder. CONCLUSION: Off-label
      drugs use is common in psychiatric OPD in our setup. Clonazepam, lorazepam, and
      trihexyphenidyl HCl were the most frequently used drugs in off-label manner.

PMID- 25767364
TI  - Assessment and comparison of clinical dental status and its impact on oral health
      related quality of life among rural and urban adults of Udaipur, India: A cross
      sectional study.
AB  - BACKGROUND: Dental diseases negatively influence people's oral health-related
      quality of life (OHRQoL) and thus their perceived need for dental care. QoL is
      increasingly acknowledged as a valid, appropriate and significant indicator of
      service need and intervention outcomes in contemporary public health research and
      practice. OBJECTIVES: (1) To assess the psychometric properties of oral health
      impact profile-14 (OHIP-14) scale among rural and urban OHIP of Udaipur
      population. (2) To assess and compare clinical dental status (dental caries,
      periodontal disease and prosthetic status) and its impacts on OHRQoL rural and
      urban population of Udaipur. MATERIALS AND METHODS: A cross-sectional descriptive
      survey was conducted among rural (600) and urban (600) population of Udaipur that
      have age ranges between 20 and 79 years, chosen from outpatient department of
      Pacific Dental College and Hospital. The OHIP-14 was tested for validity and
      reliability. Chi-square, Student's t-test, analysis of variance and multiple
      logistic regression analysis were employed for statistical analysis. RESULTS: The
      Cronbach's alpha of the scale was found to be 0.85 among the rural population and
      0.89 among the urban population. Prevalence of periodontal disease (community
      periodontal index and loss of attachment) was found greater among the rural
      population than the urban population. Urban population showed significantly
      greater proportion of subjects with prosthesis (including partial, fixed and
      total) as compared to the rural population. Among study population, OHIP-14 was
      significantly (P <= 0.05) associated with age, gender, presence of decayed teeth
      (DT), missing teeth (MT), and location. Significantly greater odds ratio (OR)
      (OHIP-14) were revealed among males (OR = 1.35, P = 0.02), urban residents (OR =
      1.13, P = 0.002), those < 45 years of age (OR = 1.23, P = 0.01), those without DT
      (OR = 1.48, P = 0.002) and without MT (OR = 1.08, P = 0.03). CONCLUSION: The
      rural and urban study subjects had a fair clinical status. The presence of dental
      caries had greatest impacts on OHRQoL. In addition, rural subjects faced greater
      impact than urban subjects.

PMID- 25767365
TI  - High acid phosphatase level in the gingival tissues of periodontitis subjects.
AB  - AIM: Periodontitis is one of the major problems slowly progressing and could
      affect 70% of the global population. The prevalence of periodontitis differs from
      mild to moderate forms of race and geographic region. The aim of this study is to
      determine the acid phosphatase (ACP) activity in the gingival tissues of
      periodontitis subjects. In this study, the activity of ACP in the gingival tissue
      of subjects with periodontitis was examined. MATERIALS AND METHODS: A total of 30
      subjects were selected for the study and are divided into group I (n = 15,
      healthy subjects in control) and in group II (n = 15, periodontitis subjects).
      The gingival tissue from group I and group II subjects were collected after the
      surgery and the ACP enzyme level was analyzed using ultraviolet
      spectrophotometer. Assessment of periodontitis was done based on periodontal
      probing depth (PPD) and clinical attachment level (CAL). The statistical analysis
      applied was independent sample t-test, P < 0.05 was considered as significant.
      RESULTS: The results of group II periodontitis subjects showed statistically
      significant increased gingival tissues ACP level when compared with the control
      group I subject. The mean levels of CAL and PPD were significantly >4 mm in
      periodontitis subjects when compared to control. CONCLUSIONS: The elevated level
      of ACP in the gingival tissue and Gram-negative microorganisms found in sub
      gingival plaque was greater in periodontitis. Based on these results, gingival
      tissue ACP level can be considered as an independent risk factor for evaluating
      the microbial status and periodontal tissue damage.

PMID- 25767366
TI  - A retrospective study on the incidences of adverse drug events and analysis of
      the contributing trigger factors.
AB  - OBJECTIVES: To retrospectively determine the extent and types of adverse drug
      events (ADEs) from the patient cases sheets and identify the contributing factors
      of medication errors. To assess causality and severity using the World Health
      Organization (WHO) probability scale and Hartwig's scale, respectively. METHODS:
      Hundred patient case sheets were randomly selected, modified version of the
      Institute for Healthcare Improvement (IHI) Global Trigger Tool was utilized to
      identify the ADEs; causality and severity were calculated utilizing the WHO
      probability scale and Hartwig's severity assessment scale, respectively. RESULTS:
      In total, 153 adverse events (AEs) were identified using the IHI Global Trigger
      Tool. Majority of the AEs are due to medication errors (46.41%) followed by 60
      adverse drug reactions (ADRs), 15 therapeutic failure incidents, and 7 over-dose
      cases. Out of the 153 AEs, 60 are due to ADRs such as rashes, nausea, and
      vomiting. Therapeutic failure contributes 9.80% of the AEs, while overdose
      contributes to 4.58% of the total 153 AEs. Using the trigger tools, we were able
      to detect 45 positive triggers in 36 patient records. Among it, 19 AEs were
      identified in 15 patient records. The percentage of AE/100 patients is 17%. The
      average ADEs/1000 doses is 2.03% (calculated). CONCLUSION: The IHI Global Trigger
      Tool is an effective method to aid provisionally-registered pharmacists to
      identify ADEs quicker.

PMID- 25767367
TI  - Antiedematogenic and antioxidant properties of high molecular weight protein sub
      fraction of Calotropis procera latex in rat.
AB  - OBJECTIVES: The aim was to evaluate the effect of high molecular weight protein
      fraction of Calotropis procera latex on edema formation and oxidative stress in
      carrageenan-induced paw inflammation. METHODS: A sub-plantar injection of
      carrageenan was given to induce edema in the hind paw of the rat. The inhibitory
      effect of high molecular weight protein fraction of C. procera latex was
      evaluated following intravenous administration (5 and 25 mg/kg body weight) and
      was compared with that of diclofenac given orally (5 mg/kg). The levels of
      reduced glutathione (GSH), thiobarbituric acid reactive substances (TBARS) and
      myeloperoxidase (MPO) were measured in the inflamed paw tissue at the end of the
      study. RESULTS: The high molecular weight protein fraction obtained from the
      latex of C. procera produced a dose-dependent inhibition of edema formation that
      was accompanied by normalization of levels of oxidative stress markers (GSH and
      TBARS) and MPO, a marker for neutrophils in the paw tissue. CONCLUSIONS: The high
      molecular weight protein fraction of C. procera latex ameliorates acute
      inflammation in the paw through its antioxidant effect.

PMID- 25767368
TI  - Isoniazid induced childhood diabetes: A rare phenomenon.
AB  - Drugs raise blood glucose concentrations via two broad mechanisms: By reducing
      insulin biosynthesis or secretion, or by reducing tissue sensitivity to insulin.
      Until date, there have been very few reported cases of isoniazid induced
      diabetes. We are presenting a case report of 6-year-old child with isoniazid
      induced diabetes who was misdiagnosed initially as a case of type 1 diabetes
      mellitus. We hereby stress that before diagnosing a patient with diabetes-type 1
      or 2, a detailed history of drug intake for any such drugs, which can cause
      hyperglycemia has to be taken. Clear cut knowledge/cognizance of all such culprit
      drugs is therefore required. 

PMID- 25767369
TI  - Elevating vitamin C content via overexpression of myo-inositol oxygenase and l
      gulono-1,4-lactone oxidase in Arabidopsis leads to enhanced biomass and tolerance
      to abiotic stresses.
AB  - l-Ascorbic acid (vitamin C) is an abundant metabolite in plant cells and tissues.
      Ascorbate functions as an antioxidant, as an enzyme cofactor, and plays essential
      roles in multiple physiological processes including photosynthesis,
      photoprotection, control of cell cycle and cell elongation, and modulation of
      flowering time, gene regulation, and senescence. The importance of this key
      molecule in regulating whole plant morphology, cell structure, and plant
      development has been clearly established via characterization of low vitamin C
      mutants of Arabidopsis, potato, tobacco, tomato, and rice. However, the
      consequences of elevating ascorbate content in plant growth and development are
      poorly understood. Here we demonstrate that Arabidopsis lines over-expressing a
      myo-inositol oxygenase or an l-gulono-1,4-lactone oxidase, containing elevated
      ascorbate, display enhanced growth and biomass accumulation of both aerial and
      root tissues. To our knowledge this is the first study demonstrating such a
      marked positive effect in plant growth in lines engineered to contain elevated
      vitamin C content. In addition, we present evidence showing that these lines are
      tolerant to a wide range of abiotic stresses including salt, cold, and heat.
      Total ascorbate content of the transgenic lines remained higher than those of
      controls under the abiotic stresses tested. Interestingly, exposure to pyrene, a
      polycyclic aromatic hydrocarbon and known inducer of oxidative stress in plants,
      leads to stunted growth of the aerial tissue, reduction in the number of root
      hairs, and inhibition of leaf expansion in wild type plants, while these symptoms
      are less severe in the over-expressers. Our results indicate the potential of
      this metabolic engineering strategy to develop crops with enhanced biomass,
      abiotic stress tolerance, and phytoremediation capabilities.

PMID- 25767370
TI  - Is There an Islamist Political Advantage?
AB  - There is a widespread presumption that Islamists have an advantage over their
      opponents when it comes to generating mass appeal and winning elections. The
      question remains, however, as to whether these advantages-or, what we refer to
      collectively as an Islamist political advantage-actually exist. We argue that-to
      the extent that Islamists have a political advantage-the primary source of this
      advantage is reputation rather than the provision of social services,
      organizational capacity, or ideological hegemony. Our purpose is not to dismiss
      the main sources of the Islamist governance advantage identified in scholarly
      literature and media accounts, but to suggest a different causal path whereby
      each of these factors individually and sometimes jointly promotes a reputation
      for Islamists as competent, trustworthy, and pure. It is this reputation for good
      governance that enables Islamists to distinguish themselves in the streets and at
      the ballot box.

PMID- 25767371
TI  - Lack of the effect of lobeglitazone, a peroxisome proliferator-activated receptor
      gamma agonist, on the pharmacokinetics and pharmacodynamics of warfarin.
AB  - AIMS: Lobeglitazone has been developed for the treatment of type 2 diabetes
      mellitus. This study was conducted to evaluate potential drug-drug interactions
      between lobeglitazone and warfarin, an anticoagulant with a narrow therapeutic
      index. METHODS: In this open-label, three-treatment, crossover study, 24 healthy
      male subjects were administered lobeglitazone (0.5 mg) for 1-12 days with
      warfarin (25 mg) on day 5 in one period. After a washout interval, subjects were
      administered warfarin (25 mg) alone in the other period. Pharmacokinetics of R-
      and S-warfarin and lobeglitazone, as well as pharmacodynamics of warfarin, as
      measured by international normalized ratio (INR) and factor VII activity, were
      assessed. RESULTS: The geometric mean ratios (GMRs) and 90% confidence intervals
      (CIs) for area under the curve from time zero to the time of the last
      quantifiable concentration (AUClast) for warfarin + lobeglitazone: warfarin alone
      were 1.0076 (90% CI: 0.9771, 1.0391) for R-warfarin and 0.9880 (90% CI: 0.9537,
      1.0235) for S-warfarin. The maximum observed plasma concentration (C max) values
      were 1.0167 (90% CI: 0.9507, 1.0872) for R-warfarin and 1.0028 (90% CI: 0.9518,
      1.0992) for S-warfarin, both of which were contained in the interval 0.80-1.25.
      Lobeglitazone had no effect on the area under the effect-time curve from time 0
      to 168 hours (AUEC) of INR and factor VII activity, as demonstrated by the GMRs
      of 1.0091 (90% CI: 0.9872, 1.0314) and 0.9355 (90% CI: 0.9028, 0.9695),
      respectively. In addition, the pharmacokinetics of lobeglitazone was also
      unaffected by warfarin. CONCLUSION: Concomitant administration of lobeglitazone
      and warfarin was well tolerated. Lobeglitazone had no meaningful effect on the
      pharmacokinetics or pharmacodynamics of warfarin. These findings indicate that
      lobeglitazone and warfarin can be coadministered without dosage adjustments for
      either drug.

PMID- 25767372
TI  - A pharmacokinetic and pharmacodynamic drug interaction between rosuvastatin and
      valsartan in healthy subjects.
AB  - PURPOSE: Valsartan, an angiotensin-receptor blocker, and rosuvastatin, a
      competitive inhibitor of the 3-hydroxy-3-methylglutaryl coenzyme A reductase, are
      frequently coadministered to treat patients with hypertension and dyslipidemia.
      The study reported here sought to evaluate the pharmacokinetic and
      pharmacodynamic interactions between rosuvastatin and valsartan in healthy Korean
      subjects. SUBJECTS AND METHODS: Thirty healthy male Korean subjects were
      administered with rosuvastatin (20 mg/day), valsartan (160 mg/day), and both
      drugs concomitantly for 4 days in a randomized, open-label, multiple-dose, three
      treatment, three-period crossover study. Plasma concentrations of rosuvastatin, N
      desmethyl rosuvastatin, and valsartan were determined using validated high
      performance liquid chromatography with tandem mass spectrometry. Lipid profiles
      and vital signs (systolic and diastolic blood pressure and pulse rate) were
      measured for the pharmacodynamic assessment. RESULTS: For rosuvastatin, the
      geometric mean ratios (90% confidence intervals [CIs]) of coadministration to
      mono-administration were 0.8809 (0.7873-0.9857) for maximum plasma concentration
      at steady state and 0.9151 (0.8632-0.9701) for area under the concentration-time
      curve (AUC) over a dosing interval at steady state. For valsartan, the geometric
      mean ratios (90% CIs) of those were 0.9300 (0.7946-1.0884) and 1.0072 (0.8893
      1.1406), respectively. There were no significant differences in the metabolic
      ratio of N-desmethyl rosuvastatin AUC to rosuvastatin AUC between
      coadministration and rosuvastatin alone. No interaction was found in terms of
      systolic or diastolic blood pressure or lipid profiles. Combined treatment with
      valsartan and rosuvastatin was generally well tolerated without serious adverse
      events. CONCLUSION: The pharmacokinetic profiles of rosuvastatin and valsartan in
      combination were comparable with those of rosuvastatin and valsartan administered
      individually, suggesting that their individual pharmacokinetics were not affected
      by their coadministration. No dose adjustment was required and the results are
      supportive of a study in a larger patient population.

PMID- 25767373
TI  - A phase 1 randomized study evaluating the effect of omeprazole on the
      pharmacokinetics of a novel 5-hydroxytryptamine receptor 4 agonist, revexepride
      (SSP-002358), in healthy adults.
AB  - BACKGROUND: About 30% of patients with gastroesophageal reflux disease continue
      to experience symptoms despite treatment with proton pump inhibitors. The 5
      hydroxytryptamine 4 receptor agonist revexepride (SSP-002358) is a novel
      prokinetic that stimulates gastrointestinal motility, which has been suggested as
      a continued cause of symptoms in these patients. The aim of this study was to
      assess whether revexepride pharmacokinetics were affected by co-administration of
      omeprazole, in preparation for a proof-of-concept evaluation of revexepride added
      to proton pump inhibitor treatment. METHODS: In this phase 1, open-label,
      randomized, two-period crossover study, healthy adults aged 18-55 years were
      given a single dose of revexepride 1 mg or revexepride 1 mg + omeprazole 40 mg.
      Pharmacokinetic parameters were assessed for up to 48 hours after administration
      of the investigational product. Adverse events, clinical chemistry and hematology
      parameters, electrocardiograms, and vital signs were monitored. RESULTS: In
      total, 42 participants were enrolled and 40 completed the study. The median age
      was 24 years (18-54 years), 55% were women and 93% were white. The
      pharmacokinetic parameters of revexepride were similar without or with omeprazole
      co-administration. The mean area under the plasma concentration-time curve from
      time 0 to infinity (AUC0-infinity) was 23.3 ng . h/mL (standard deviation [SD]:
      6.33 ng . h/mL) versus 24.6 ng . h/mL (SD: 6.31 ng . h/mL), and maximum plasma
      concentrations (Cmax) were 3.89 ng/mL (SD: 1.30 ng/mL) and 4.12 ng/mL (SD: 1.29
      ng/mL) in participants without and with omeprazole, respectively. For AUC0
      infinity and Cmax, the 90% confidence intervals for the ratios of geometric least
      squares means (with:without omeprazole) were fully contained within the pre
      defined equivalence limits of 0.80-1.25. Mean apparent terminal phase half-life
      was 9.95 hours (SD: 2.06 hours) without omeprazole, and 11.0 hours (SD: 3.25
      hours) with omeprazole. CONCLUSION: Co-administration of the 5-hydroxytryptamine
      receptor 4 agonist revexepride with omeprazole did not affect the
      pharmacokinetics of revexepride in healthy adults.

PMID- 25767374
TI  - Antitumoral materials with regenerative function obtained using a layer-by-layer
      technique.
AB  - A layer-by layer technique was successfully used to obtain
      collagen/hydroxyapatite-magnetite-cisplatin (COLL/HAn-Fe3O4-CisPt, n=1-7)
      composite materials with a variable content of hydroxyapatite intended for use in
      the treatment of bone cancer. The main advantages of this system are the
      possibility of controlling the rate of delivery of cytostatic agents, the
      presence of collagen and hydroxyapatite to ensure more rapid healing of the
      injured bone tissue, and the potential for magnetite to be a passive antitumoral
      component that can be activated when an appropriate external electromagnetic
      field is applied. In vitro cytotoxicity assays performed on the COLL/HAn-Fe3O4
      CisPt materials obtained using a layer-by layer method confirmed their
      antitumoral activity. Samples with a higher content of hydroxyapatite had more
      antitumoral activity because of their better absorption of cisplatin and
      consequently a higher amount of cisplatin being present in the matrices. 

PMID- 25767375
TI  - In vitro and in vivo anti-angiogenic activity of girinimbine isolated from
      Murraya koenigii.
AB  - Girinimbine is a carbazole alkaloid isolated from the stem bark and root of
      Murraya koenigii. Here we report that girinimbine is an inhibitor of angiogenic
      activity both in vitro and in vivo. MTT results showed that girinimbine inhibited
      proliferation of human umbilical vein endothelial cells, while results from
      endothelial cell invasion, migration, tube formation, and wound healing assays
      demonstrated significant time- and dose-dependent inhibition by girinimbine. A
      proteome profiler array done on girinimbine-treated human umbilical vein
      endothelial cells showed that girinimbine had mediated regulation of pro
      angiogenic and anti-angiogenic proteins. The anti-angiogenic potential of
      girinimbine was also evidenced in vivo in the zebrafish embryo model wherein
      girinimbine inhibited neo vessel formation in zebrafish embryos following 24
      hours of exposure. Together, these results showed that girinimbine could
      effectively suppress angiogenesis, suggestive of its therapeutic potential as a
      novel angiogenesis inhibitor. 

PMID- 25767376
TI  - Danusertib, a potent pan-Aurora kinase and ABL kinase inhibitor, induces cell
      cycle arrest and programmed cell death and inhibits epithelial to mesenchymal
      transition involving the PI3K/Akt/mTOR-mediated signaling pathway in human
      gastric cancer AGS and NCI-N78 cells.
AB  - Gastric cancer is the second leading cause of cancer-related death worldwide,
      with a poor response to current chemotherapy. Danusertib is a pan-inhibitor of
      the Aurora kinases and a third-generation Bcr-Abl tyrosine kinase inhibitor with
      potent anticancer effects, but its antitumor effect and underlying mechanisms in
      the treatment of human gastric cancer are unknown. This study aimed to
      investigate the effects of danusertib on cell growth, apoptosis, autophagy, and
      epithelial to mesenchymal transition and the molecular mechanisms involved in
      human gastric cancer AGS and NCI-N78 cells. The results showed that danusertib
      had potent growth-inhibitory, apoptosis-inducing, and autophagy-inducing effects
      on AGS and NCI-N78 cells. Danusertib arrested AGS and NCI-N78 cells in G2/M
      phase, with downregulation of expression of cyclin B1 and cyclin-dependent kinase
      1 and upregulation of expression of p21 Waf1/Cip1, p27 Kip1, and p53. Danusertib
      induced mitochondria-mediated apoptosis, with an increase in expression of
      proapoptotic protein and a decrease in antiapoptotic proteins in both cell lines.
      Danusertib induced release of cytochrome c from the mitochondria to the cytosol
      and triggered activation of caspase 9 and caspase 3 in AGS and NCI-N78 cells.
      Further, danusertib induced autophagy, with an increase in expression of beclin 1
      and conversion of microtubule-associated protein 1A/1B-light chain 3 (LC3-I) to
      LC3-II in both cell lines. Inhibition of phosphatidylinositol 3-kinase
      (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) and p38
      mitogen-activated protein kinase pathways as well as activation of 5' AMP
      activated protein kinase contributed to the proautophagic effect of danusertib in
      AGS and NCI-N78 cells. SB202191 and wortmannin enhanced the autophagy-inducing
      effect of danusertib in AGS and NCI-N78 cells. In addition, danusertib inhibited
      epithelial to mesenchymal transition with an increase in expression of E-cadherin
      and a decrease in expression of N-cadherin in both cell lines. Taken together,
      danusertib has potent inducing effects on cell cycle arrest, apoptosis, and
      autophagy, but has an inhibitory effect on epithelial to mesenchymal transition,
      with involvement of signaling pathways mediated by PI3K/Akt/mTOR, p38 mitogen
      activated protein kinase, and 5' AMP-activated protein kinase in AGS and NCI-N78
      cells. 

PMID- 25767377
TI  - Antitumor activity of SA12, a novel peptide, on SKBr-3 breast cancer cells via
      the mitochondrial apoptosis pathway.
AB  - Breast cancer is considered to be the most common malignancy in women. Treatment
      of breast cancer has been focused on molecular targeted therapy, and anticancer
      peptides are considered to be some of the most promising candidate drugs. In the
      current study, we used mRNA-peptide display technology to screen antibreast
      cancer peptides and identified a novel peptide, SA12, which showed significant
      activity in the inhibition of proliferation and induction of apoptosis in SKBr-3
      breast cancer cells. The mechanism by which SA12 peptide triggers apoptosis was
      further investigated using a pull-down assay, reverse transcription-polymerase
      chain reaction, and Western blotting analysis. The results demonstrated that this
      peptide could interact with tumor-associated proteins MECP2 and CDC20B, which
      further induced apoptosis of tumor cells via the mitochondrial pathway involving
      the Bcl-2 family and related caspases. We propose that the novel SA12 peptide has
      the potential to provide a new strategy for the development of targeted therapy
      in breast cancer. 

PMID- 25767379
TI  - Frailty in patients with acute coronary syndrome: comparison between tools for
      comprehensive geriatric assessment and the Tilburg Frailty Indicator.
AB  - PURPOSE: It is a known fact that age is a strong predictor of adverse events in
      acute coronary syndrome (ACS). In this context, the main risk factor in elderly
      patients, ie, frailty syndrome, gains special importance. The availability of
      tools to identify frail people is relevant for both research and clinical
      purposes. The purpose of this study was to investigate the correlation of a scale
      for assessing frailty - the Tilburg Frailty Indicator (TFI) and its domains
      (mental and physical) - with other research tools commonly used for comprehensive
      geriatric assessment in patients with ACS. PATIENTS AND METHODS: The study
      covered 135 people and was carried out in the cardiology ward at T Marciniak
      Lower Silesian Specialist Hospital in Wroclaw, Poland. The patients were admitted
      with ACS. ST segment elevation myocardial infarction and non-ST segment elevation
      myocardial infarction were defined by the presence of certain conditions in
      reference to the literature. The Polish adaptation of the TFI was used for the
      frailty syndrome assessment, which was compared to other single measures used in
      geriatric assessment: the Mini-Mental State Examination (MMSE), the Hospital
      Anxiety and Depression Scale (HADS), and Katz Index of Independence in Activities
      of Daily Living (ADLs). RESULTS: The mean TFI value in the studied group amounted
      to 7.13+/-2.81 (median: 7, interquartile range: 5-9, range [0, 14]). Significant
      correlations were demonstrated between the values of the TFI and other scales:
      positive for HADS (r=0.602, P<0.001) and the reverse for MMSE (r=-0.603, P<0.001)
      and IADL (r=-0.462, P<0.001). Patients with a TFI score >=5 revealed considerably
      higher values on HADS (P<0.001) and considerably lower values on the MMSE
      (P<0.001) and IADL scales (P=0.001). CONCLUSION: The results for the TFI comply
      with the results of other scales (MMSE, HADS, ADL, IADL), which confirm the
      credibility of the Polish adaptation of the tool. Stronger correlations were
      observed for mental components and the mental scales turned out to be
      independently related to the TFI in a multidimensional analysis.

PMID- 25767378
TI  - Antithrombotic therapy in elderly patients with non-valvular atrial fibrillation:
      a pilot study.
AB  - OBJECTIVE: Non-valvular atrial fibrillation (NVAF) is one common arrhythmia in
      the elderly. However, use of antithrombotic therapy in this population is not
      well known in the People's Republic of China. This study aimed at investigating
      antithrombotic therapy status in elderly patients with NVAF in our hospital.
      METHODS: A cross-sectional study of consecutive geriatric patients aged >=60
      years with NVAF who discharged from our hospital between January 2012 and
      December 2013 were collected. CHA2DS2-VASc score (cardiac failure or dysfunction,
      hypertension, age >=75 [doubled], diabetes, stroke or transient ischemic attack
      [doubled], vascular disease, age 65-74, and sex category [female]) was used to
      analyze antithrombotic indication. RESULTS: We consecutively collected data of
      1,000 discharged elderly patients (>=60 years) with NVAF (mean age 75.3+/-8.0
      years, 75 years or older 54.7%, female 42.7%). The proportion of paroxysmal
      atrial fibrillation and non-paroxysmal atrial fibrillation (persistent or
      permanent) patients were 39.4% and 60.6%, respectively. Among 1,000 patients,
      29.1% received oral anticoagulant therapy (OAT), including warfarin (27.8%) and
      novel oral anticoagulants (1.3%), 39.5% of patients received antiplatelet
      therapy, and 31.4% received neither therapy. Based on CHA2DS2-VASc score for
      stroke risk stratification, 68.9% patients with score >=1 and 70.2% patients with
      score >=2 received antithrombotic therapy, while the rates of OAT were 29.1% and
      29.5%, respectively. Among patients with high stroke risk, those with paroxysmal
      atrial fibrillation were less likely to receive OAT compared with the patients
      with non-paroxysmal atrial fibrillation (19.5% vs 35.7%, P<0.001). The patients
      >=75 years old had lower rate of OAT than the patients <75 years old (25.8% vs
      34.8%, P=0.003). The patients with coronary artery disease had lower rate of OAT
      than the patients without coronary artery disease (24.4% vs 33.4%, P=0.003). Sex
      and history of stroke or transient ischemic attack had no effect on the use of
      OAT (30.8% vs 27.9%, P=0.326 and 28.8% vs 29.8%, P=0.761, respectively).
      CONCLUSION: OAT in elderly patients with NVAF in our hospital is underused,
      especially in those patients with higher risk of stroke.

PMID- 25767380
TI  - Effects of different resistance training frequencies on flexibility in older
      women.
AB  - OBJECTIVE: The main purpose of the investigation reported here was to analyze the
      effect of resistance training (RT) performed at different weekly frequencies on
      flexibility in older women. PARTICIPANTS AND METHODS: Fifty-three older women
      (>=60 years old) were randomly assigned to perform RT either two (n=28; group
      "G2x"), or three (n=25; group "G3x") times per week. The RT program comprised
      eight exercises in which the participants performed one set of 10-15 repetitions
      maximum for a period of 12 weeks. Anthropometric, body-composition, and
      flexibility measurements were made at baseline and post-study. The flexibility
      measurements were obtained by a fleximeter. RESULTS: A significant group-by-time
      interaction (P<0.01) was observed for frontal hip flexion, in which G3x showed a
      higher increase than G2x (+12.8% and +3.0%, respectively). Both groups increased
      flexibility in cervical extension (G2x=+19.1%, G3x=+20.0%), right hip flexion
      (G2x=+14.6%, G3x=+15.9%), and left hip flexion (G2x=+25.7%, G3x=+19.2%), with no
      statistical difference between groups. No statistically significant differences
      were noted for the increase in skeletal muscle mass between training three versus
      two times a week (+7.4% vs +4.4%, respectively). CONCLUSION: Twelve weeks of RT
      improves the flexibility of different joint movements in older women, and the
      higher frequency induces greater increases for frontal hip flexion.

PMID- 25767381
TI  - Influence of indacaterol on daily physical activity in patients with untreated
      chronic obstructive pulmonary disease.
AB  - BACKGROUND: Indacaterol, a once-daily, long-acting beta2-agonist, may improve not
      only respiratory function, dyspnea symptoms, and quality of life, but also
      physical activity for patients with chronic obstructive pulmonary disease (COPD).
      This study aimed to evaluate the effect of 12-week indacaterol therapy on daytime
      physical activity in patients with untreated COPD. METHODS: The subjects were
      stable and untreated COPD outpatients with a percent predicted forced expiratory
      volume in 1 second (%FEV1) below 80%. Baseline assessments included clinical
      assessment, respiratory function testing, arterial blood gas analysis, the COPD
      assessment test (CATTM), and the Medical Outcomes Study 36-Item Short-Form Health
      Survey, Japanese version 2 (SF-36v2((r))). Patients underwent monitoring by
      uniaxial accelerometer before and after 12 weeks once-daily inhalation of
      indacaterol 150 MUg/day. RESULTS: Eighteen patients were evaluable. Patient
      characteristics included a mean age of 74.2 years, and three patients were
      current smokers. Indacaterol improved mean (+/- standard deviation [SD]) %FEV1
      from 55.2% (+/-17.9%) to 61.0% (+/-17.3%) (P=0.003), CAT scores from 16.4 (+/
      10.2) points to 12.4 (+/-8.2) points (P=0.04), some scales of the SF-36v2
      (physical component summary, 41.6+/-9.7 points to 45.1+/-7.9 points, P=0.03), and
      number of daily steps (3,311.5+/-2,103.3 steps/day to 3,841.8+/-2,096.8
      steps/day, P=0.02), but did not affect daily energy expenditure (85.0+/-77.2 kcal
      change to 90.9+/-56.8 kcal, P=0.29) or exercise duration of an intensity of level
      1 or more (36.4+/-23.9 minutes increase to 40.8+/-21.6 minutes, P=0.12).
      CONCLUSION: Twelve weeks of indacaterol improved respiratory function and quality
      of life, but did not significantly affect physical activity in patients with
      moderate-to-severe COPD.

PMID- 25767382
TI  - A pilot study: mindfulness meditation intervention in COPD.
AB  - Living well with chronic obstructive pulmonary disease (COPD) requires people to
      manage disease-related symptoms in order to participate in activities of daily
      living. Mindfulness practice is an intervention that has been shown to reduce
      symptoms of chronic disease and improve accurate symptom assessment, both of
      which could result in improved disease management and increased wellness for
      people with COPD. A randomized controlled trial was conducted to investigate an 8
      week mindful meditation intervention program tailored for the COPD population and
      explore the use of breathing timing parameters as a possible physiological
      measure of meditation uptake. Results demonstrated that those randomized to the
      mindful meditation intervention group (N=19) had a significant increase in
      respiratory rate over time as compared to those randomized to the wait-list group
      (N=22) (P=0.045). It was also found that the mindful meditation intervention
      group demonstrated a significant decrease in level of mindfulness over time as
      compared to the wait-list group (P=0.023). When examining participants from the
      mindful meditation intervention who had completed six or more classes, it was
      found that respiratory rate did not significantly increase in comparison to the
      wait-list group. Furthermore, those who completed six or more classes (N=12)
      demonstrated significant improvement in emotional function in comparison to the
      wait-list group (P=0.032) even though their level of mindfulness did not improve.
      This study identifies that there may be a complex relationship between breathing
      parameters, emotion, and mindfulness in the COPD population. The results describe
      good feasibility and acceptability for meditation interventions in the COPD
      population. 

PMID- 25767383
TI  - Amoxicillin concentrations in relation to beta-lactamase activity in sputum
      during exacerbations of chronic obstructive pulmonary disease.
AB  - BACKGROUND: Acute exacerbations of chronic obstructive pulmonary disease (COPD)
      are often treated with antibiotics. Theoretically, to be maximally effective, the
      antibiotic concentration at sites of infection should exceed the minimum
      inhibitory concentration at which 90% of the growth of potential pathogens is
      inhibited (MIC90). A previous study showed that most hospitalized COPD patients
      had sputum amoxicillin concentrations <LMIC90 when treated with
      amoxicillin/clavulanic acid. Those with adequate sputum concentrations had better
      clinical outcomes. Low amoxicillin concentrations can be caused by beta-lactamase
      activity in the lungs. This study investigated whether patients with sputum
      amoxicillin concentrations <MIC90 had higher beta-lactamase activity in sputum
      than patients with a concentration >=MIC90. METHODS: In total, 23 patients
      hospitalized for acute exacerbations of COPD and treated with
      amoxicillin/clavulanic acid were included. Sputum and serum samples were
      collected at day 3 of treatment to determine beta-lactamase activity in sputum
      and amoxicillin concentrations in both sputum and serum. RESULTS: We found no
      difference in beta-lactamase activity between patients with sputum amoxicillin
      concentrations <MIC90 and >=MIC90 (P=0.79). Multivariate logistic regression
      analysis showed no significant relationship between beta-lactamase activity and
      sputum amoxicillin concentrations <MIC90 or >=MIC90 (odds ratio 0.53; 95%
      confidence interval 0.23-1.2; P=0.13). Amoxicillin concentrations were <MIC90 in
      78% of sputum samples and in 30% of serum samples. CONCLUSION: In patients
      treated with amoxicillin/clavulanic acid for an acute exacerbation of COPD,
      sputum beta-lactamase activity did not differ between those with sputum
      amoxicillin concentrations <MIC90 or >=MIC90. The finding that the majority of
      patients had sputum amoxicillin concentrations <MIC90 suggests that current
      treatment with antibiotics for acute exacerbations of COPD should be optimized.

PMID- 25767384
TI  - Effect of a single nucleotide polymorphism in miR-146a on COX-2 protein
      expression and lung function in smokers with chronic obstructive pulmonary
      disease.
AB  - OBJECTIVE: To evaluate the effect of a single nucleotide polymorphism (rs2910164)
      in the miR-146a precursor on the expression level of miR-146a, cyclooxygenase-2
      (COX2), and production of prostaglandin E2 (PGE2) in lung tissue harvested from
      smokers with chronic obstructive pulmonary disease, as well as the lung function
      and disease stages from the same patient population. METHODS AND RESULTS: One
      hundred and sixty-eight smokers with diagnosed chronic obstructive pulmonary
      disease were recruited. The patients were genotyped for rs2910164 polymorphism
      using Sanger sequencing, and their lung function/disease stages were evaluated
      following Global Initiative for Chronic Obstructive Lung Disease (GOLD) criteria.
      Meanwhile, messenger ribonucleic acid and protein expression levels of miR-146a
      and COX2 as well as PGE2 production were determined in 66 lung tissue samples
      collected in the patients who received surgical treatment. We confirmed that COX2
      is a validated target of miR-146a in human fibroblast cells, and identified the
      differential expression patterns of miR-146a and COX2 in each rs2910164 genotype
      group. We observed a significant association between rs2910164 in miR-146a and
      the levels of either COX2 or PGE2 using real-time polymerase chain reaction and
      Western blot. Consistently, we were able to demonstrate that the rs2910164 single
      nucleotide polymorphism has a functional effect on the baseline lung function in
      the study population. CONCLUSION: In the present study, the rs2910164 CC and GC
      genotype was found to be associated with an improved lung function and milder
      disease stages, at least partially, mediated by its ability to increase in COX2
      expression and PGE2 production.

PMID- 25767385
TI  - Calcium-activated gene transfection from DNA/poly(amic acid-co-imide) complexes.
AB  - In this study, we synthesized a water-soluble poly(amic acid-co-imide) (PA-I)
      from ethylenediaminetetraacetic dianhydride (EDTA) and 2,2'
      (ethylenedioxy)bis(ethylamine) that possesses comparable transfection efficiency
      to that of polyethylenimine (PEI), when prepared in combination with divalent
      calcium cations. The polycondensation of monomers afforded poly(amic acid) (PA)
      precursors, and subsequent thermal imidization resulted in the formation of PA-I.
      At a polymer/DNA ratio (indicated by the molar ratio of nitrogen in the polymer
      to phosphate in DNA) of 40, complete retardation of the DNA band was observed by
      gel electrophoresis, indicating the strong association of DNA with PA-I. A zeta
      potential of -22 mV was recorded for the PA-I polymer solution, and no apparent
      cytotoxicity was observed at concentrations up to 500 MUg.mL(-1). In the presence
      of divalent Ca(2+), the transfection efficiency of PA-I was higher than that of
      PA, due to the formation of a copolymer/Ca(2+)/DNA polyplex and the reduction in
      negative charge due to thermal cyclization. Interestingly, a synergistic effect
      of Ca(2+) and the synthesized copolymer on DNA transfection was observed. The use
      of Ca(2+) or copolymer alone resulted in unsatisfactory delivery, whereas the
      formation of three-component polyplexes synergistically increased DNA
      transfection. Our findings demonstrated that a PA-I/Ca(2+)/DNA polyplex could
      serve as a promising candidate for gene delivery. 

PMID- 25767386
TI  - Antileukemic effect of zerumbone-loaded nanostructured lipid carrier in WEHI-3B
      cell-induced murine leukemia model.
AB  - Cancer nanotherapy is progressing rapidly with the introduction of many
      innovative drug delivery systems to replace conventional therapy. Although the
      antitumor activity of zerumbone (ZER) has been reported, there has been no
      information available on the effect of ZER-loaded nanostructured lipid carrier
      (NLC) (ZER-NLC) on murine leukemia cells. In this study, the in vitro and in vivo
      effects of ZER-NLC on murine leukemia induced with WEHI-3B cells were
      investigated. The results from 3-[4,5-dimethylthiazol-2-yl]-2,5
      diphenyltetrazolium bromide, Hoechst 33342, Annexin V, cell cycle, and caspase
      activity assays showed that the growth of leukemia cells in vitro was inhibited
      by ZER-NLC. In addition, outcomes of histopathology, transmission electron
      microscopy, and Tdt-mediated dUTP nick-end labeling analyses revealed that the
      number of leukemia cells in the spleen of BALB/c leukemia mice significantly
      decreased after 4 weeks of oral treatment with various doses of ZER-NLC. Western
      blotting and reverse-transcription quantitative polymerase chain reaction assays
      confirmed the antileukemia effects of ZER-NLC. In conclusion, ZER-NLC was shown
      to induce a mitochondrial-dependent apoptotic pathway in murine leukemia. Loading
      of ZER in NLC did not compromise the anticancer effect of the compound,
      suggesting ZER-NLC as a promising and effective delivery system for treatment of
      cancers. 

PMID- 25767387
TI  - An efficient method for in vitro gene delivery via regulation of cellular
      endocytosis pathway.
AB  - Transfection efficiency was the primary goal for in vitro gene delivery mediated
      by nonviral gene carriers. Here, we report a modified gene transfection method
      that could greatly increase the efficiency of, and accelerate the process
      mediated by, 25 kDa branched polyethyleneimine and LipofectamineTM 2000 in a
      broad range of cell strains, including tumor, normal, primary, and embryonic stem
      cells. In this method, the combination of transfection procedure with optimized
      complexation volume had a determinant effect on gene delivery result. The
      superiorities of the method were found to be related to the change of cellular
      endocytosis pathway and decrease of particle size. The efficient and simple
      method established in this study can be widely used for in vitro gene delivery
      into cultured cells. We think it may also be applicable for many more nonviral
      gene delivery materials than polyethyleneimine and liposome. 

PMID- 25767388
TI  - Magnetic resonance hypointensive signal primarily originates from extracellular
      iron particles in the long-term tracking of mesenchymal stem cells transplanted
      in the infarcted myocardium.
AB  - PURPOSE: The long-lasting hypointensities in cardiac magnetic resonance (CMR)
      were believed to originate from superparamagnetic iron oxide (SPIO)-engulfed
      macrophages during long-term stem cell tracking. However, the iron clearance
      capacity of the ischemic heart was limited. Therefore, we speculated that the
      extracellular SPIO particles may also be involved in the generation of false
      positive signals. METHODS AND RESULTS: Male swine mesenchymal stem cells (MSCs)
      were incubated with SPIO for 24 hours, and SPIO labeling had no significant
      effects on either cell viability or differentiation. In vitro studies showed that
      magnetic resonance failed to distinguish SPIO from living SPIO-MSCs or dead SPIO
      MSCs. Two hours after the establishment of the female swine acute myocardial
      infarction model, 2*10(7) male SPIO-labeled MSCs (n=5) or unlabeled MSCs (n=5)
      were transextracardially injected into the infarcted myocardium at ten distinct
      sites. In vivo CMR with T2 star weighted imaging-flash-2D sequence revealed a
      signal void corresponding to the initial SPIO-MSC injection sites. At 6 months
      after transplantation, CMR identified 32 (64%) of the 50 injection sites, where
      massive Prussian blue-positive iron deposits were detected by pathological
      examination. However, iron particles were predominantly distributed in the
      extracellular space, and a minority was distributed within CD68-positive
      macrophages and other CD68-negative cells. No sex-determining region Y DNA of
      donor MSCs was detected. CONCLUSION: CMR hypointensive signal is primarily caused
      by extracellular iron particles in the long-term tracking of transplanted MSCs
      after myocardial infarction. Consideration should be given to both the false
      positive signal and the potential cardiac toxicity of long-standing iron deposits
      in the heart.

PMID- 25767389
TI  - Management of chronic hepatitis C virus infection in patients with end-stage
      renal disease: a review.
AB  - Infection with hepatitis C virus (HCV) is highly prevalent in chronic kidney
      disease (CKD) patients, mainly in those on hemodialysis (HD). The seroprevalence
      of HCV in developing countries ranges between 7% and 40%. Risk factors for this
      infection in the CKD population include the number of blood transfusions,
      duration of end-stage renal disease (ESRD), and prevalence of HCV in HD. Chronic
      HCV infection in patients with ESRD is associated with an increase in morbidity
      and mortality in the pre and post kidney transplant periods. The increase in
      mortality is directly associated with liver complications and an elevated
      cardiovascular risk in HCV-infected patients on hemodialysis. Antiviral treatment
      may improve the prognosis of patients with HCV, and standard interferon remains
      the cornerstone of treatment. Treatment of HCV in patients with CKD is complex,
      but achieving a sustained viral response may decrease the frequency of
      complications after transplantation. It appears that HCV-infected patients who
      remain on maintenance dialysis are at increased risk of death compared with HCV
      patients undergoing renal transplantation. 

PMID- 25767390
TI  - Risk of breast cancer recurrence in patients receiving manual lymphatic drainage:
      a hospital-based cohort study.
AB  - BACKGROUND: This retrospective cohort study evaluated whether manual lymphatic
      drainage (MLD) therapy increases the risk of recurrence of breast cancer.
      METHODS: We analyzed 1,106 women who were diagnosed with stage 0-3 breast cancer
      between 2007 and 2011 and experienced remission after surgery and adjuvant
      therapy. The patients were divided into two groups: group A (n=996), in which
      patients did not participate in any MLD therapy, regardless of whether they
      developed breast cancer-related lymphedema (BCRL) after cancer treatment; and
      group B (n=110), in which patients participated in MLD therapy for BCRL. All
      patients were monitored until October 2013 to determine whether breast cancer
      recurrence developed, including local or regional recurrence and distant
      metastasis. Patients who developed cancer recurrence prior to MLD therapy were
      excluded from analysis. Risk factors associated with cancer recurrence were
      evaluated using Cox proportional hazards models. RESULTS: During the monitoring
      period, 166 patients (15.0%) developed cancer recurrence, including 154 (15.5%)
      in group A and 12 (10.9%) in group B. The median period from surgery to cancer
      recurrence was 1.85 (interquartile range 1.18-2.93) years. Independent risk
      factors for cancer recurrence were tumor histological grading of grade 3, high
      number (>=3) of axillary lymph node invasion, and a large tumor size (>5 cm).
      Factors protecting against recurrence were positive progesterone receptor status
      and receiving radiation therapy. Receiving MLD therapy was not an outcome factor
      in multivariate analyses (hazard ratio 0.71, 95% confidence interval 0.39-1.29,
      P=0.259). CONCLUSION: MLD is a gentle procedure that does not increase the risk
      of breast cancer recurrence in patients who develop BCRL.

PMID- 25767391
TI  - Update on therapeutic management of idiopathic pulmonary fibrosis.
AB  - Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive diffuse parenchymal
      lung disease of unknown origin, with a mortality rate exceeding that of many
      cancers. The diagnostic process is complex and relies on the clinician
      integrating clinical, laboratory, radiological, and histological data. In the
      last decade, major advances in our understanding of the pathogenesis of IPF have
      shifted the paradigm from a primarily inflammatory process evolving to fibrosis
      to a condition driven by aberrant wound healing following alveolar epithelial
      cell injury that results in scarring of the lung, architectural distortion, and
      irreversible loss of function. Improved understanding of disease pathogenesis has
      led to the identification of several therapeutic targets and the design of high
      quality clinical trials evaluating novel compounds. However, the results of these
      studies have been mostly disappointing, probably due to the plethora of
      mediators, growth factors, and signaling pathways involved in the fibrotic
      process. Most recently, pirfenidone and nintedanib, two compounds with
      pleiotropic anti-fibrotic properties, have been proven effective in reducing
      functional decline and disease progression in IPF. This is a major breakthrough.
      Nevertheless, we still have a long way to go. In fact, neither pirfenidone nor
      nintedanib is a cure for IPF, and most patients continue to progress despite
      treatment. As such, comprehensive care of patients with IPF, including management
      of concomitant conditions and physical debility, as well as timely referral for
      lung transplantation, remains essential. Several agents with a high potential are
      currently being tested, and many more are ready for clinical trials. Their
      completion is critical for achieving the ultimate goal of curing patients with
      IPF. 

PMID- 25767392
TI  - Therapeutic effect of hybrid training of voluntary and electrical muscle
      contractions in middle-aged obese women with nonalcoholic fatty liver disease: a
      pilot trial.
AB  - BACKGROUND: Exercise training is an effective therapy for nonalcoholic fatty
      liver disease (NAFLD). Hybrid training (HYB) of voluntary and electrical muscle
      contractions was developed to prevent disuse atrophy during space flight. HYB can
      be applied to obtain a strength training effect accompanying articular movement.
      In this pilot study, we aimed to investigate the therapeutic efficacy of HYB in
      NAFLD. METHODS: A total of 15 middle-aged obese women with NAFLD who had no
      improvement in serum alanine aminotransferase levels and/or liver fat deposition
      after 12 weeks of lifestyle counseling participated in an HYB program. HYB of the
      quadriceps and hamstrings was conducted for 20 minutes twice a week for 24 weeks.
      RESULTS: NAFLD patients showed attenuated intramyocellular lipid levels in the
      quadriceps after the HYB intervention (-15.5%). Levels of leptin (-17.4%), tumor
      necrosis factor-alpha (-23.2%), and interleukin-6 (-30.5%) were also decreased
      after the intervention. HYB led to a significant body weight reduction (-4.7%),
      which in turn was associated with a significant decrease in serum alanine
      aminotransferase (-35.8%), gamma-glutamyl transpeptidase (-21.6%), ferritin (
      16.0%), oxidative stress (-17.8%) levels, and insulin resistance values (-2.7%).
      CONCLUSION: In NAFLD, HYB exerts an antiobesity effect and attenuates liver
      dysfunction and insulin resistance in association with an increase in muscle
      strength and a decrease in ectopic muscle fat. Therefore, HYB has great potential
      as a new type of exercise therapy for liver disease in patients with NAFLD.

PMID- 25767393
TI  - Quality improvements in decreasing medication administration errors made by
      nursing staff in an academic medical center hospital: a trend analysis during the
      journey to Joint Commission International accreditation and in the post
      accreditation era.
AB  - BACKGROUND: Medication errors may occur during prescribing, transcribing,
      prescription auditing, preparing, dispensing, administration, and monitoring.
      Medication administration errors (MAEs) are those that actually reach patients
      and remain a threat to patient safety. The Joint Commission International (JCI)
      advocates medication error prevention, but experience in reducing MAEs during the
      period of before and after JCI accreditation has not been reported. METHODS: An
      intervention study, aimed at reducing MAEs in hospitalized patients, was
      performed in the Second Affiliated Hospital of Zhejiang University, Hangzhou,
      People's Republic of China, during the journey to JCI accreditation and in the
      post-JCI accreditation era (first half-year of 2011 to first half-year of 2014).
      Comprehensive interventions included organizational, information technology,
      educational, and process optimization-based measures. Data mining was performed
      on MAEs derived from a compulsory electronic reporting system. RESULTS: The
      number of MAEs continuously decreased from 143 (first half-year of 2012) to 64
      (first half-year of 2014), with a decrease in occurrence rate by 60.9% (0.338%
      versus 0.132%, P<0.05). The number of MAEs related to high-alert medications
      decreased from 32 (the second half-year of 2011) to 16 (the first half-year of
      2014), with a decrease in occurrence rate by 57.9% (0.0787% versus 0.0331%,
      P<0.05). Omission was the top type of MAE during the first half-year of 2011 to
      the first half-year of 2014, with a decrease by 50% (40 cases versus 20 cases).
      Intravenous administration error was the top type of error regarding
      administration route, but it continuously decreased from 64 (first half-year of
      2012) to 27 (first half-year of 2014). More experienced registered nurses made
      fewer medication errors. The number of MAEs in surgical wards was twice that in
      medicinal wards. Compared with non-intensive care units, the intensive care units
      exhibited higher occurrence rates of MAEs (1.81% versus 0.24%, P<0.001).
      CONCLUSION: A 3-and-a-half-year intervention program on MAEs was confirmed to be
      effective. MAEs made by nursing staff can be reduced, but cannot be eliminated.
      The depth, breadth, and efficiency of multidiscipline collaboration among
      physicians, pharmacists, nurses, information engineers, and hospital
      administrators are pivotal to safety in medication administration. JCI
      accreditation may help health systems enhance the awareness and ability to
      prevent MAEs and achieve successful quality improvements.

PMID- 25767394
TI  - Matrix metalloproteinases in atherosclerosis: role of nitric oxide, hydrogen
      sulfide, homocysteine, and polymorphisms.
AB  - Atherosclerosis is an inflammatory process that involves activation of matrix
      metalloproteinases (MMPs); MMPs degrade collagen and allow for smooth-muscle cell
      migration within a vessel. Moreover, this begets an accumulation of other
      cellular material, resulting in occlusion of the vessel and ischemic events to
      tissues in need of nutrients. Homocysteine has been shown to activate MMPs via an
      increase in oxidative stress and acting as a signaling molecule on receptors like
      the peroxisome proliferator activated receptor-gamma and N-methyl-D-aspartate
      receptor. Nitric oxide has been shown to be beneficial in some cases of
      deactivating MMPs. However, in other cases, it has been shown to be harmful.
      Further studies are warranted on the scenarios that are beneficial versus
      destructive. Hydrogen sulfide (H2S) has been shown to decrease MMP activities in
      all cases in the literature by acting as an antioxidant and vasodilator. Various
      MMP-knockout and gene-silencing models have been used to determine the function
      of the many different MMPs. This has allowed us to discern the role that each MMP
      has in promoting or alleviating pathological conditions. Furthermore, there has
      been some study into the MMP polymorphisms that exist in the population. The
      purpose of this review is to examine the role of MMPs and their polymorphisms on
      the development of atherosclerosis, with emphasis placed on pathways that involve
      nitric oxide, hydrogen sulfide, and homocysteine. 

PMID- 25767395
TI  - Adherence to guideline-recommended therapies among patients with diverse
      manifestations of vascular disease.
AB  - BACKGROUND: Current guidelines recommend aspirin, statins, angiotensin-converting
      enzyme inhibitors (ACEIs), and smoking abstinence for all patients with vascular
      disease. There is little data on the variation in adherence to guideline
      recommended therapies among patients with different clinical manifestations of
      vascular disease. PURPOSE: To analyze the variation in adherence to guideline
      recommended therapies among patients with diverse manifestations of vascular
      disease. METHODS: We analyzed a comprehensive database of all patients with
      critical limb ischemia, claudication, acute limb ischemia, carotid artery
      stenosis, subclavian artery stenosis, renal artery stenosis, or mesenteric
      ischemia who underwent angiography between 2006 and 2013 at a multidisciplinary
      vascular center. RESULTS: Among 1,114 patients with vascular disease, adherence
      to guideline-recommended therapy at time of angiography included use of aspirin
      in 936 (84%), statins in 753 (68%), ACEIs in 673 (60%), and smoking abstinence in
      788 (71%). A total of 335 (30%) patients utilized all four guideline-recommended
      therapies. Adherence to four guideline-recommended therapies was lowest among
      patients with acute limb ischemia (14%) and highest among patients with renal
      artery stenosis (37%). Among all patients with vascular disease, the range of
      adherence to individual guidelines was 64%-91% for aspirin, 43%-83% for statins,
      49%-66% for ACEIs, and 47%-78% for smoking abstention. CONCLUSION: The majority
      of patients with diverse manifestations of vascular disease take aspirin and
      abstain from smoking while fewer patients are prescribed ACEIs and statins. Among
      the current recommendations, statins have the widest variation in adherence. Less
      than one-third of patients with diverse manifestations of vascular disease are
      prescribed all four guideline-recommended therapies.

PMID- 25767396
TI  - Cell death in response to antimetabolites directed at ribonucleotide reductase
      and thymidylate synthase.
AB  - New agent development, mechanistic understanding, and combinatorial partnerships
      with known and novel modalities continue to be important in the study of
      pancreatic cancer and its improved treatment. In this study, known antimetabolite
      drugs such as gemcitabine (ribonucleotide reductase inhibitor) and 5-fluorouracil
      (thymidylate synthase inhibitor) were compared with novel members of these two
      drug families in the treatment of a chemoresistant pancreatic cancer cell line
      PANC-1. Cellular survival data, along with protein and messenger ribonucleic acid
      expression for survivin, XIAP, cIAP1, and cIAP2, were compared from both the cell
      cytoplasm and from exosomes after single modality treatment. While all
      antimetabolite drugs killed PANC-1 cells in a time- and dose-dependent manner,
      neither family significantly altered the cytosolic protein level of the four
      inhibitors of apoptosis (IAPs) investigated. Survivin, XIAP, cIAP1, and cIAP2
      were found localized to exosomes where no significant difference in expression
      was recorded. This inability for significant and long-lasting expression may be a
      reason why pancreatic cancer lacks responsiveness to these and other cancer
      killing agents. Continued investigation is required to determine the
      responsibilities of these IAPs in their role in chemoresistance in pancreatic
      adenocarcinoma. 

PMID- 25767397
TI  - Comparison between three oxaliplatin-based regimens with bevacizumab in patients
      with metastatic colorectal cancer.
AB  - BACKGROUND: A previous pivotal Phase III study (NO16966) demonstrated the benefit
      of the addition of bevacizumab (BV) to oxaliplatin-based regimens in metastatic
      colorectal cancer (MCRC). Our study evaluated the safety and efficacy of three
      oxaliplatin-based chemotherapy regimens (FOLFOX4 [intravenous twice-bolus and
      twice-infusional 5-fluorouracil/folinic acid plus oxaliplatin], mFOLFOX6
      [intravenous once-bolus and once-infusional 5-fluorouracil/folinic acid plus
      oxaliplatin], and XELOX [capecitabine plus oxaliplatin]) plus BV in the first
      line treatment of MCRC patients. METHODS: Patients with MCRC who started
      treatment between June 2007 and September 2010 were evaluated in this
      retrospective cohort study. We also evaluated early objective tumor response
      (EOTR) within 12 weeks, which was defined as a relative change of >=30% in the
      sum of the longest diameters of target lesions when compared with baseline. The
      primary study endpoints were progression-free survival (PFS) and response rate.
      RESULTS: A total of 185 patients received the following chemotherapy: FOLFOX4 +
      BV (FF4 arm, n=85), mFOLFOX6 + BV (FF6 arm, n=40), and XELOX + BV (XELOX arm,
      n=60). The overall response rates were 61.2%, 72.5%, and 75.0% (95% confidence
      interval: 50.6%-71.8%, 58.0%-87.0%, and 63.7%-86.3%). Median PFS was 18.0, 15.5,
      and 13.7 months, respectively (log-rank: P=0.254; data cut-off: May 2013).
      Patients with EOTR (n=117) had significantly better PFS than those without-EOTR
      (n=68) (17.5 versus 12.7 months, P=0.004). CONCLUSION: This study suggests that
      these three BV plus oxaliplatin-based treatments might have comparable benefit in
      terms of tumor response and PFS. Moreover, EOTR may be a predictive factor for
      PFS in patients with MCRC.

PMID- 25767398
TI  - The role of miR-29b in cancer: regulation, function, and signaling.
AB  - MicroRNAs (miRNAs) are endogenous small non-coding RNAs with the capacity to
      regulate gene expression post-transcriptionally. The miRNA-29 family consists of
      miR-29a, miR-29b, and miR-29c, among which miR-29b is the most highly expressed
      and is found at two genomic loci. Recently, numerous studies have demonstrated
      that aberrant expression of miR-29b is common in the majority of human cancers.
      miR-29b is known to critically affect cancer progression by functioning as a
      tumor suppressor. However, it may also act as an oncogene under certain
      conditions. In this review, we illustrate the role of miR-29b in cancer
      regulation, function, and signaling. This is the first review highlighting the
      role of miR-29b in cancer. Our review aims to summarize the effects of miR-29b on
      cancer activity and its interactions with target genes and signaling pathways, as
      well as to provide therapeutic implications for overcoming cancer
      chemoresistance. 

PMID- 25767399
TI  - Accumulation of p53 is prognostic for aromatase inhibitor resistance in early
      stage postmenopausal patients with ER-positive breast cancer.
AB  - OBJECTIVE: Studies have indicated that p53 protein accumulation exerts an adverse
      effect on the survival of breast cancer patients; however, the prognostic value
      of p53 protein accumulation for aromatase inhibitor (AI) resistance in ER
      positive breast cancer is uncertain. METHODS: The expression level of p53 protein
      was detected by immunohistochemistry in primary early-stage ER-positive breast
      tumor specimens from 293 postmenopausal breast cancer patients who received first
      line AI treatment (letrozole, anastrozole, or exemestane) until relapse, and
      analysis was performed to determine whether expression of p53 protein affected
      the response to endocrine therapy. RESULTS: Of the 293 invasive ductal
      carcinomas, 65.4% were positive for p53 protein expression. All patients received
      AI therapy as first-line treatment until relapse. The 5-year disease-free
      survival rates in p53-positive and p53-negative patients were 78% and 89%,
      respectively. Patients with primary breast tumors that had p53 protein
      accumulation showed significantly more resistance to AI treatment (hazard
      ratio=1.729, 95% confidence interval=1.038-2.880, P=0.035). CONCLUSION: This
      study demonstrated that p53 protein accumulation was helpful in choosing patients
      who may benefit from AI treatment and is a prognostic marker in ER-positive early
      stage breast cancer.

PMID- 25767400
TI  - Cost-effectiveness of using an extensively hydrolyzed casein formula plus the
      probiotic Lactobacillus rhamnosus GG compared to an extensively hydrolyzed
      formula alone or an amino acid formula as first-line dietary management for cow's
      milk allergy in the US.
AB  - OBJECTIVES: The aim was to estimate the cost-effectiveness of using an
      extensively hydrolyzed casein formula (eHCF) plus the probiotic Lactobacillus
      rhamnosus GG (eHCF + LGG; Nutramigen LGG) compared to an eHCF alone (Nutramigen)
      and an amino acid formula (AAF; Neocate) as first-line dietary management for
      cow's milk allergy (CMA) in the US. METHODS: Using a cohort study design, the
      analysis was based on the case records of 136 eHCF-fed, 59 eHCF + LGG-fed, and
      217 matched AAF-fed infants extracted from the Truven Health MarketScan((r))
      Commercial Claims Database (a nationally representative database of the
      commercially insured population of the US). Clinical outcomes and health care
      resource use (with corresponding costs at 2012 prices), following first-line
      dietary management with each formula, were estimated over 12 months from the
      start of feeding. Differences in infants' outcomes and resource use between
      groups were adjusted for any differences in baseline covariates. RESULTS: Infants
      were <6 months of age at presentation. Fifty-six percent of eHCF + LGG-fed
      infants were estimated to have been successfully managed by 9 months compared to
      38% of eHCF-fed infants and 35% of AAF-fed infants (P<0.05 and P=0.003
      respectively). Infants in the AAF group used significantly more health care
      resources and prescribed drugs than infants in the other two groups. The
      estimated cost of managing a CMA infant over the first 12 months following the
      start of feeding was $3,577, $3,781, and $6,255 for an eHCF + LGG-fed, eHCF-fed,
      and AAF-fed infant, respectively. Parents' costs accounted for up to 10% of the
      total costs and the remainder was incurred by insurers. The analyses were robust
      to plausible changes in all variables. CONCLUSION: Using real world evidence,
      initial dietary management with eHCF + LGG appears to afford a more cost
      effective use of health care resources than initial dietary management with eHCF
      or AAF since it releases health care resources for alternative use within the
      system and reduces costs without impacting on the time needed to manage the
      allergy.

PMID- 25767401
TI  - Withdrawal of sulfonylureas from patients with type 2 diabetes receiving long
      term sulfonylurea and insulin combination therapy results in deterioration of
      glycemic control: a randomized controlled trial.
AB  - BACKGROUND: The benefit of sulfonylureas (SUs) to patients with type 2 diabetes
      mellitus receiving long-term insulin treatment is unclear. This study evaluated
      glycemic control and beta-cell function after SU withdrawal in these patients.
      METHODS: In this 8-week randomized controlled study, patients with type 2
      diabetes who had been treated with insulin for at least 3 years plus moderate to
      high doses of SUs were randomly assigned to withdrawal (n=16) or continuation
      (n=16) of SUs. Clinical characteristics, glycemic control, hypoglycemic events,
      and insulin secretion, including homeostasis model assessment of beta-cell
      function (HOMA-B) score, C-peptide concentration, and Matsuda index, were
      evaluated at baseline and after 2 and 8 weeks. RESULTS: Thirty patients (16 in
      the SU withdrawal group and 14 in the SU continuation group) completed the study.
      Median duration of diabetes was 17 (range 5-40) years. Baseline clinical
      characteristics, glycemic control, and HOMA-B were similar in the two groups, but
      the mean fasting C-peptide concentration was higher in the SU withdrawal group.
      After 8 weeks, the SU withdrawal group showed a significant increase in mean
      glycosylated hemoglobin levels from 7.8%+/-0.5% (62+/-5 mmol/mol) to 8.6%+/-1.2%
      (71+/-13 mmol/mol; P=0.002), whereas the SU continuation group showed a slight
      but not significant increase from 7.7%+/-0.5% (61+/-5 mmol/mol) to 7.9%+/-1.2%
      (63+/-13 mmol/mol; P=0.37). Insulin secretion, as measured by C-peptide and HOMA
      B, decreased by 18% and 36%, respectively, in the SU withdrawal group.
      Hypoglycemic events were significantly more frequent in the SU continuation group
      whereas body weight did not change significantly in either group. CONCLUSION:
      Withdrawal of SU from patients with type 2 diabetes receiving long-term
      combination treatment with SU and insulin resulted in deterioration of glycemic
      control and insulin secretion.

PMID- 25767403
TI  - Bicytopenia as a paraneoplastic syndrome for pseudomyxoma peritonei. Hematologic
      manifestations of a subtle disease.

PMID- 25767402
TI  - From observational to analytical morphology of the stratum corneum: progress
      avoiding hazardous animal and human testings.
AB  - BACKGROUND: In cosmetic science, noninvasive sampling of the upper part of the
      stratum corneum is conveniently performed using strippings with adhesive-coated
      discs (SACD) and cyanoacrylate skin surface strippings (CSSSs). METHODS: Under
      controlled conditions, it is possible to scrutinize SACD and CSSS with
      objectivity using appropriate methods of analytical morphology. These procedures
      apply to a series of clinical conditions including xerosis grading, comedometry,
      corneodynamics, corneomelametry, corneosurfametry, corneoxenometry, and dandruff
      assessment. RESULTS: With any of the analytical evaluations, SACD and CSSS
      provide specific salient information that is useful in the field of cosmetology.
      In particular, both methods appear valuable and complementary in assessing the
      human skin compatibility of personal skincare products. CONCLUSION: A set of
      quantitative analytical methods applicable to the minimally invasive and low-cost
      SACD and CSSS procedures allow for a sound assessment of cosmetic effects on the
      stratum corneum. Under regular conditions, both methods are painless and do not
      induce adverse events. Globally, CSSS appears more precise and informative than
      the regular SACD stripping.

PMID- 25767404
TI  - Case of cytomegalovirus colitis in an immunocompetent patient: a rare cause of
      abdominal pain and diarrhea in the elderly.
AB  - Cytomegalovirus (CMV) colitis usually occurs in immunocompromised patients after
      undergoing organ transplantation or chemotherapy. We report the case of a 60-year
      old immunocompetent Japanese woman who presented with abdominal pain and bloody
      diarrhea. She was initially diagnosed as having ischemic colitis with
      pseudomembranous colitis on the basis of her symptoms, Clostridium difficile
      antigen positivity, and colonoscopic findings, which showed ulcer formation from
      the sigmoid colon to rectum. In spite of bowel rest and administration of
      metronidazole, her symptoms did not improve. On follow-up colonoscopy,
      ulcerations remained unchanged. Biopsy of the ulceration revealed CMV-infected
      cells leading to a diagnosis of CMV colitis. CMV colitis is a rare but possible
      differential diagnosis in immunocompetent patients. We recommend endoscopic
      biopsy in a case of refractory abdominal pain and bloody diarrhea. 

PMID- 25767405
TI  - Risk factors and effective management of preeclampsia.
AB  - Preeclampsia, a hypertensive disorder of pregnancy is estimated to complicate 2%
      8% of pregnancies and remains a principal cause of maternal and fetal morbidity
      and mortality. Preeclampsia may present at any gestation but is more commonly
      encountered in the third trimester. Multiple risk factors have been documented,
      including: family history, nulliparity, egg donation, diabetes, and obesity.
      Significant progress has been made in developing tests to predict risk of
      preeclampsia in pregnancy, but these remain confined to clinical trial settings
      and center around measuring angiogenic profiles, including placental growth
      factor or newer tests involving metabolomics. Less progress has been made in
      developing new treatments and therapeutic targets, and aspirin remains one of the
      few agents shown to consistently reduce the risk of developing preeclampsia. This
      review serves to discuss recent advances in risk factor identification,
      prediction techniques, and management of preeclampsia in antenatal, intrapartum,
      and postnatal patients. 

PMID- 25767406
TI  - Sodium hypochlorite accident resulting in life-threatening airway obstruction
      during root canal treatment: a case report.
AB  - AIM: This case report describes a serious and life-threatening complication of
      the use of sodium hypochlorite as an irrigation solution in root canal therapy.
      SUMMARY: This case report describes a hypochlorite accident that occurred in a
      healthy 42-year-old female who was undergoing routine root canal therapy for the
      lower right central incisor (tooth #41). After approximately 1 hour of irrigation
      with 3% sodium hypochlorite (for a total of 12 cc), the patient complained of
      severe pain and burning in the lip. The swelling progressed over the next 8 hours
      to involve the sublingual and submental fascial spaces with elevation of the
      tongue and resultant upper airway obstruction. The patient was intubated and
      remained on mechanical ventilation for 3 days. She recovered without any skin
      necrosis or nerve deficits. KEY LEARNING POINTS: This case report highlights the
      importance of carefully performing root canal irrigation with sodium hypochlorite
      to avoid complications. Careful injection without pressure, the use of proper
      rubber dam isolation, and the use of the endodontic needle are necessary to avoid
      this type of complication. Although it is a safe root canal irrigation solution,
      its use may lead to life-threatening complications. Early recognition and
      management of the untoward effects of sodium hypochlorite are vital for the
      patient's safety.

PMID- 25767407
TI  - Successful focal ablation in a patient with electrical storm in the early
      postinfarction period: case report.
AB  - Electrical storm (ES) is associated with a poor prognosis if it occurs in the
      early postinfarction period (within 4 weeks). There are limited data on the
      efficacy and safety of catheter ablation in the early period. In the patients
      with postinfarction cardiomyopathy, ventricular tachycardia (VT) is usually
      caused by re-entry through slowly conducting tissue within areas of a myocardial
      scar, whereas for the early postinfarction period, the underlying mechanism of ES
      is not fully understood. We report a case of ES for which macroreentry was
      excluded as a mechanism of VT because of the clinical and electrophysiological
      properties of the tachycardia. The tachycardia was terminated by focal
      radiofrequency catheter ablation of the earliest site. The total procedure time
      was only 35 minutes. During a 12-month follow-up period, the patient has remained
      free of monomorphic VT episodes. On the basis of this case, we aimed to discuss
      the underlying mechanism of ES in the early postinfarction period and to evaluate
      the role of radiofrequency catheter ablation as a primary approach for treating
      ES. 

PMID- 25767408
TI  - N-acetylcysteine overdose after acetaminophen poisoning.
AB  - N-acetylcysteine (NAC) is used widely and effectively in oral and intravenous
      forms as a specific antidote for acetaminophen poisoning. Here we report a rare
      case of iatrogenic NAC overdose following an error in preparation of the
      solution, and describe its clinical symptoms. Laboratory results and are
      presented and examined. A 23-year-old alert female patient weighing 65 kg
      presented to the emergency ward with weakness, lethargy, extreme fatigue, nausea,
      and dizziness. She had normal arterial blood gas and vital signs. An excessive
      dosage of NAC over a short period of time can lead to hemolysis,
      thrombocytopenia, and acute renal failure in patients with normal glucose-6
      phosphate dehydrogenase, and finally to death. Considering the similarity between
      some of the clinical symptoms of acetaminophen overdose and NAC overdose, it is
      vitally important for the administration phases and checking of the patient's
      symptoms to be carried out attentively and cautiously. 

PMID- 25767409
TI  - Is there an association between insomnia symptoms, aggressive behavior, and
      suicidality in adolescents?
AB  - PURPOSE: Sleep disturbances are a common problem during adolescence. Often there
      is a relationship with the mental health of the affected person. The existing
      literature concerning the link between sleep disturbances and aggressive behavior
      and sleep disturbances and suicidality during adolescence shows no clear results.
      The present study tested a mediation model to prove the relation between sleep
      problems, aggressive behavior, and suicidality during adolescence. To take the
      link between suicidality and depression into account, the amount of depressive
      symptoms was included into the mediation model. METHODS: A sample of 93
      adolescents aged 14-18 years (30% male) was studied. A survey was conducted to
      interview the adolescents about their mental health, sleep-related behaviors,
      aggressive behavior, and suicidality. RESULTS: Sleep problems and suicidality
      measures were significantly related to each other. Furthermore, aggressive
      behavior and suicidality showed a significant relationship. The expected link
      between sleep problems and aggressive behavior was not significant. For the
      mediation model, no significant influence of aggressive behavior on the
      relationship between the amount of sleep problems and suicidality was found.
      However, the impact of depressive symptoms on the relationship between sleep
      problems and suicidality was significant. CONCLUSION: Sleep problems and overall
      suicidality in adolescents are significantly connected, even after adjusting for
      several possible influencing factors. Aggressive behavior could not be confirmed
      as a mediator for the association between sleep problems and suicidality in
      adolescents. Further studies to examine the link between insomnia symptoms,
      aggressive behavior, and suicidality in adolescents are necessary.

PMID- 25767410
TI  - Identifying the prevalence, trajectory, and determinants of psychological
      distress in extremity sarcoma.
AB  - Objective. Extremity sarcoma (ES) is a rare cancer that presents with unique
      challenges. This study was performed to identify the prevalence, trajectory, and
      determinants of distress and characterise sources of stress in this cohort.
      Methods. Consecutive patients with ES were prospectively recruited between May
      2011 and December 2012. Questionnaires were administered during initial diagnosis
      and then six months and one year after surgery. Results. Distress was reported by
      about a third of our cohort and associated with poorer physical function, poorer
      quality of life, and pain. In addition to fears regarding mortality and life role
      changes, the most common sources of stress were centered on dissatisfaction with
      the healthcare system, such as frustrations with a lack of communication with the
      hospital regarding appointments and lack of education regarding management and
      outcomes. Conclusions. Psychological distress presents early in the cancer
      journey and persists up to one year after surgery. Distress is associated with
      negative outcomes. Active screening and effective interventions are necessary to
      improve outcomes. Sources of stress have been identified that may be amenable to
      targeted interventions. 

PMID- 25767412
TI  - High prevalence of workplace violence among nurses working at public health
      facilities in Southern Ethiopia.
AB  - BACKGROUND: The rising rate of workplace violence in health care facilities has
      become a major problem for health care providers including nurses. However,
      evidences are lacking in Ethiopia particularly in the study area. The aim of this
      study is to assess the prevalence and associated factors of workplace violence
      among nurses working at health care facilities in Hawassa City Administration,
      Southern Ethiopia. METHODS: An institution-based cross-sectional study was
      conducted on 660 randomly selected nurses working at public health facilities in
      Hawassa City Administration in April 2014. A pre-tested and structured
      questionnaire was used to collect the data. Data were entered using EPI-Info and
      exported to SPSS for further analysis. Descriptive statistics were done. Logistic
      regression analyses were used to see the association between different variables
      and the outcome variable. Odds ratios with 95% Confidence Interval (CI) were
      computed to determine the presence and strength of the association. RESULTS: In
      this study, the prevalence of workplace violence was 29.9% [95% CI: 26.5, 33.5)]
      of which physical violence accounted for 36 (18.22%), verbal abuse for 172
      (89.58%) and sexual harassment for 25 (13.02%). Female sex [AOR=2.00, 95% CI:
      (1.28, 2.39)], short work experience [AOR=8.86, 95% CI: (3.47, 22.64)], age group
      of 22-25 [AOR=4.17, 95% CI: (2.46, 7.08)], age group of (26-35) [AOR=1.9, 95% CI
      (1.16, 3.1)], work in emergency [(AOR=4.28, 95% CI: (1.39, 4.34)] and work in the
      Inpatient Department [(AOR=2.11, 95% CI: (1.98, 2.64)] were the factors
      positively associated with workplace violence. CONCLUSIONS: A significant
      proportion of nurses faced violence while providing care at in public health
      facilities. Being female, younger age, short work experience, and assignment in
      emergency and inpatient departments were positively associated with workplace
      violence. Policy makers and stakeholders should focus on workplace violence
      prevention strategies.

PMID- 25767413
TI  - A tool to support meaningful person-centred activity for clients with dementia -
      a Delphi study.
AB  - BACKGROUND: This paper reports on a study to validate the concept of the
      'Activity Support Tool' that aimed to assist dementia service workers to identify
      and act upon the support needs of people with dementia living alone, in line with
      the person-centred ideal. METHODS: The tool was part of a two-stage exploratory
      qualitative study, which used interview and observational data from seven people
      with dementia living alone. Findings highlighted that people with dementia use
      objects and spaces within their homes to maintain or re-enact identities from the
      past. Thematic results from interviews were translated into a tool, with
      construct validation using the Delphi technique. Eighteen expert health
      professionals received round one of the questionnaire and six participants
      completed round three. The first round directed our focus towards
      operationalizing the person-centred ideal of dementia care. RESULTS: The tool was
      considered by almost all advisory panel members to be a potentially valuable
      resource for helping to address impediments to integrated, effective and person
      centred dementia care. Specific strengths identified were simplicity, person
      centeredness and applicability across service settings. Issues of concern
      included practicability, risk management, gender stereotyping and terminology.
      The results support the findings of previous research into the intuitive and
      ethical appeal, but problematic applicability, of person-centred dementia
      services. CONCLUSION: Health professionals with a range of service-related
      expertise found the concept of person-centred care compelling, but required
      tangible, enduring structures to translate the ideal into practical action. The
      tool now requires further research to test its usefulness in practice.

PMID- 25767411
TI  - Effects of parecoxib on analgesia benefit and blood loss following open
      prostatectomy: a multicentre randomized trial.
AB  - BACKGROUND: This multi-centre, prospective, randomized, double-blind, placebo
      controlled study was designed to test the hypotheses that parecoxib improves
      patients' postoperative analgesia without increasing surgical blood loss
      following radical open prostatectomy. METHODS: 105 patients (64 +/- 7 years old)
      were randomized to receive either parecoxib or placebo with concurrent morphine
      patient controlled analgesia. Cumulative opioid consumption (primary objective)
      and the overall benefit of analgesia score (OBAS), the modified brief pain
      inventory short form (m-BPI-sf), the opioid-related symptom distress scale (OR
      SDS), and perioperative blood loss (secondary objectives) were assessed. RESULTS:
      In each group 48 patients received the study medication for 48 hours
      postoperatively. Parecoxib significantly reduced cumulative opioid consumption by
      24% (43 +/- 24.1 mg versus 57 +/- 28 mg, mean +/- SD, p=0.02), translating into
      improved benefit of analgesia (OBAS: 2(0/4) versus 3(1/5.25), p=0.01), pain
      severity (m-BPI-sf: 1(1/2) versus 2(2/3), p < 0.01) and pain interference (m-BPI
      sf: 1(0/1) versus 1(1/3), p=0.001), as well as reduced opioid-related side
      effects (OR-SDS score: 0.3(0.075/0.51) versus 0.4(0.2/0.83), p=0.03). Blood loss
      was significantly higher at 24 hours following surgery in the parecoxib group
      (4.3 g?dL(-1) (3.6/4.9) versus (3.2 g?dL(-1) (2.4/4.95), p=0.02). CONCLUSIONS:
      Following major abdominal surgery, parecoxib significantly improves patients'
      perceived analgesia. Parecoxib may however increase perioperative blood loss.
      Further trials are needed to evaluate the effects of selective cyclooxygenase-2
      inhibitors on blood loss. TRIAL REGISTRATION: ClinicalTrials.gov Identifier:
      NCT00346268.

PMID- 25767414
TI  - Long-term home visiting with vulnerable young mothers: an interpretive
      description of the impact on public health nurses.
AB  - BACKGROUND: The Nurse-Family Partnership (NFP) is a targeted, nurse home
      visitation program for young, low-income, first-time mothers. While the
      effectiveness of the NFP has been established in the United States, and is
      currently being evaluated in the Canadian public health care system, we have
      minimal understanding of how work of this nature impacts public health nurses
      (PHNs), an essential component of this program delivery model, on both
      professional and personal levels. METHODS: This two-phase study consisted of a
      qualitative secondary analysis of data from five focus groups conducted with PHNs
      (N = 6) who delivered the NFP intervention as part of a pilot study assessing
      feasibility and acceptability conducted in Hamilton, Ontario. The second phase,
      an interpretive description of individual interviews with the PHNs (N = 10) who
      have delivered the NFP in this context, further explored themes identified in the
      first phase. A practice, problem and needs analysis was conducted to describe and
      understand the phenomenon and promote sustainability of PHNs in this practice
      environment. Conventional content analysis was used to code and categorize data
      in the two datasets. RESULTS: The nurse-client relationship, the core elements
      and structure of the NFP program and support of NFP colleagues were described as
      rewarding factors, while workload and workplace factors were identified as
      significant contributors to stress. PHNs described transforming their nursing
      practice through redefining success and shifting to a philosophy where the client
      is the expert of her own life. PHNs described the personal impact of worry about
      clients and doubt about their effectiveness in addressing client concerns. High
      levels of satisfaction were described in relation to the depth and intensity of
      relationships with clients and seeing them succeed over time. CONCLUSIONS: PHNs
      are impacted in multiple ways by their work with vulnerable, young mothers. The
      study findings have implications for identification of strategies to support PHNs
      in reducing staff turnover, PHN burnout, secondary traumatic stress and
      compassion fatigue, and improving program delivery.

PMID- 25767415
TI  - Family Social Status and Preschoolers' Persistence: The Role of Maternal Values
      and Quality of Parenting.
AB  - Children who develop persistence in the preschool years are likely to function
      more effectively during the transition into school. In this study of 231 3-year
      old children and their mothers, we examined the relations among family social
      status, maternal values of self-direction, and quality of parenting and
      children's persistence in challenging tasks. Results of SEM path analysis
      indicated that family social status was related to maternal values of self
      direction, which in turn were associated with the quality of maternal cognitive
      stimulation and emotional support and child persistence at preschool-age. Family
      social status and maternal values were indirectly related to child persistence
      through emotional support. Focusing on parental values of self-direction and
      provision of support during challenging tasks may help to reduce the gap in
      school success between children from lower and higher social status families.

PMID- 25767416
TI  - Barbed Sutures and Tendon Repair-a Review.
AB  - INTRODUCTION: Traumatic tendon lacerations are a common problem encountered by
      hand surgeons worldwide. Although the use of barbed suture to repair tendon
      lacerations has gained theoretical popularity in recent years, there is little
      information available regarding the safety, efficacy, longevity, or complications
      encountered when used in tenorraphy. In this study, we review the available
      literature on the use of barbed suture in tendon repair. METHODS: Studies
      conducted between 1980 and 2014 were identified using several databases,
      including EMBASE, SCOPUS, MEDLINE, and Web of Science. Keywords used to search
      for appropriate studies included the following: barbed, v loc, quill, tendon,
      tendon injuries, suture, tenorraphy, injury, and laceration, in various
      combinations. RESULTS: Our initial literature search identified 47 articles, and
      8 were deemed appropriate for review after applying our exclusion criteria. The
      data from each of the articles is reviewed for the following major
      categories:Maximum load to failureMode of failureLoad to 2-mm gapChange in cross
      sectional areaType of repair. CONCLUSIONS: Barbed suture tenorraphy has a myriad
      of theoretical advantages, supported by varying ex vivo studies, as compared to
      traditional techniques. However, due to the non-uniformity in current studies and
      the lack of available data in a live model, we are unable to argue for or against
      barbed suture tenorraphy. We believe our review provides the most in-depth
      analysis of barbed suture tenorraphy to date, illuminates the potential
      advantages of using barbed sutures, and highlights the need for further
      investigation into this technique.

PMID- 25767417
TI  - A brief review of extensor tendon injuries specific to the pediatric patient.
AB  - Extensor tendon injuries in the pediatric population require careful evaluation
      and treatment. This article focuses on the differences in injury type and
      treatment of pediatric versus adult extensor tendon injuries. A detailed history
      and physical examination is crucial in the management of extensor tendon injuries
      of the young patient. Treatment of pediatric extensor tendon injuries depends
      largely on the site of injury. A majority of these injuries may be treated with
      splinting or primary repair. Treatment methods that require high compliance must
      be adjusted for the young child. 

PMID- 25767418
TI  - Composite grafting for pediatric fingertip injuries.
AB  - BACKGROUND: Fingertip injuries are common in the pediatric population. Composite
      grafting is a frequently used technique for distal amputations in children given
      the reported success rate. We sought to study the early clinical results of
      composite grafting for fingertip injuries in the pediatric population. METHODS: A
      retrospective review was performed over a 5-year period at a tertiary care
      pediatric hospital to identify those patients who underwent composite grafting of
      fingertip injuries. Patients were included if they were 18 years old or younger
      and sustained an injury distal to the distal interphalangeal joint (or thumb
      interphalangeal joint). Demographic information was recorded. Graft viability was
      characterized as no take, partial take, or complete take. The number of secondary
      procedures and number and duration of follow-up appointments were recorded.
      Hypothesis testing was done using ordinal logistic regression analysis. RESULTS:
      Thirty-nine patients underwent fingertip composite grafting. The mean age was 5.9
      years (1-18 years); there were 24 males (61.5 %) and 15 females (38.5 %).
      Thirteen patients had no graft take (33.3 %), 23 patients had partial take (59.0
      %), and three patients had complete take (7.7 %). Only four patients underwent
      secondary revision (10 %). The median number of follow-up appointments was 3 and
      the average follow-up time was 4.5 months. Age did not appear to have a
      statistically significant influence on graft take. CONCLUSIONS: Fingertip
      composite grafts rarely take completely even in young children. Despite poor
      viability, however, most patients will have at least partial graft take and do
      not undergo additional reconstructive procedures.

PMID- 25767419
TI  - Mini-open versus extended open release for severe carpal tunnel syndrome.
AB  - BACKGROUND: This study aims to compare surgical outcomes of severe carpal tunnel
      syndrome (CTS) treated with mini-incision versus extensile release. METHODS: The
      method employed in this study was a retrospective review of patients with severe
      CTS, defined by electrophysiologic studies showing non-recordable distal sensory
      latency of the median nerve. Patients underwent either a mini-incision (2 cm)
      release of the transverse carpal ligament (group 1) or extensile release proximal
      to the wrist flexion crease (group 2). Exclusion criteria included prior carpal
      tunnel release, use of muscle flap, multiple concurrent procedures, or a prior
      diagnosis of peripheral neuropathy. Group 1 included 70 wrists (40 females, 30
      males). Group 2 included 64 wrists (35 females, 29 males). Reported outcomes
      included pre- and post-operative grip strength as well as Boston Carpal Tunnel
      Questionnaires (BCTQ). RESULTS: Patients in group 1 had a 22.6 % increase in grip
      strength postoperatively (4.5 months +/- 5.0), while patients in group 2 had a
      59.3 % increase (10.0 months +/- 6.9). BCTQ surveys from group 1 (n = 46)
      demonstrated a symptom severity score of 12.93 and functional status score of
      9.39 at an average follow-up of 41.9 +/- 10.6 months. Group 2 (n = 42) surveys
      demonstrated averages of 12.88 and 9.10 at 43.1 +/- 11.6 months. One patient in
      the mini-incision cohort required revision surgery after 2 years, while no
      patient in the extended release cohort underwent revision. CONCLUSION: No
      significant differences between the two procedures with regard to patient-rated
      symptom severity or functional status outcomes were found. Both techniques were
      demonstrated to be effective treatment options for severe CTS.

PMID- 25767420
TI  - A non-scalpel technique for minimally invasive surgery: percutaneously looped
      thread transection of the transverse carpal ligament.
AB  - PURPOSE: This study aims to develop an alternate technique for improving the
      surgical procedure of carpal tunnel release. METHOD: The transverse carpal
      ligament is transected by utilizing a piece of thread looped percutaneously under
      the visualization of ultrasound. The procedure, the thread carpal tunnel release
      (TCTR), was performed on 34 hands of 20 patients. Self-administrated Levine-Katz
      questionnaire was used for assessing the symptom severity and functional status
      of the outcomes. RESULTS: TCTR was performed in each case with no unintended
      consequences. The average duration for a procedure was 7 min, excluding time of
      preparation. Significant improvements in subjective sensibility were reported
      within 24 h, and sleep quality improved for all cases. There were no
      postoperative complications. The scores of questionnaire 3 months postoperatively
      were comparable to the literature controls. CONCLUSION: TCTR is a safe and
      effective minimally invasive surgery performed under local anesthesia in a clinic
      based procedure room and results in only one-needle entrance point at the wrist
      and one-needle exit point in the palm. The feature of the procedure includes the
      potentials of reduced risk of iatrogenic injury, reduced surgical cost, and
      reduced patient recovery time. The study has shown encouraging promise for
      optimizing the technique of carpal tunnel release, and more clinical trials are
      necessary to confirm the findings.

PMID- 25767421
TI  - Prospective comparison of the six-item carpal tunnel symptoms scale and portable
      nerve conduction testing in measuring the outcomes of treatment of carpal tunnel
      syndrome with steroid injection.
AB  - BACKGROUND: We prospectively studied patients clinically diagnosed with carpal
      tunnel syndrome (CTS) and treated with the injection of corticosteroid into their
      carpal tunnel in order to compare changes in the six-item CTS symptoms scale and
      portable nerve conduction study (NCS) parameters as outcome tools. Our pilot
      study was the first to assess the utility of the six-item CTS symptom scale (CTS
      6) with steroid injections as a patient-directed outcome measure for the
      treatment of CTS. METHODS: We enrolled patients who presented to our county
      hospital orthopedic surgery clinic from August 2012 through August 2013. The
      patients were clinically diagnosed with CTS. After completing the six-item CTS
      symptoms scale questionnaire, portable NCS was obtained. Each patient then
      received an injection of 1 ml of triamcinolone acetonide 40 mg/ml mixed with 1 ml
      of 1 % lidocaine into the carpal tunnel. Six weeks postinjection, each patient
      repeated a CTS-6 questionnaire and underwent a repeat portable NCS. The CTS-6 and
      NCS results were analyzed using the paired samples t test. A Pearson correlation
      was used to assess the correlation between the changes in the CTS-6 and the NCS
      measurements. Statistical significance was set at P < 0.05. RESULTS: Thirty-two
      wrists in 20 patients were evaluated. There was a statistically significant
      difference between the CTS-6 scores before and after injection. There were also
      statistically significant changes in the five of the NCS parameters. None of the
      correlations between the CTS-6 and the NCS parameters were statistically
      significant. CONCLUSIONS: The six-item CTS symptoms scale and portable NCS are
      both useful measures for evaluating the results of steroid injections. The CTS-6
      is an effective tool because of its ease of use, low cost, correspondence with
      changes in NCS, and ability to monitor the outcome of steroid treatment for
      carpal tunnel syndrome.

PMID- 25767422
TI  - Use of peripheral nerve transfers in tetraplegia: evaluation of feasibility and
      morbidity.
AB  - BACKGROUND: Peripheral nerve transfers are being used to improve upper extremity
      function in cervical spinal cord injury (SCI) patients. The purpose of this study
      was to evaluate feasibility and perioperative complications following these
      procedures. METHODS: Eligible SCI patients with upper extremity dysfunction were
      assessed and followed for a minimum of 3 months after surgery. Data regarding
      demographics, medical history, physical examination, electrodiagnostic testing,
      intraoperative nerve stimulation, recipient nerve histomorphometry, surgical
      procedure, and complications were collected. RESULTS: Seven patients had surgery
      on eight limbs, mean age of 28 +/- 9.9 years and mean time from SCI injury of 5.1
      +/- 5.2 years. All patients had volitional elbow flexion and no volitional hand
      function. The nerve to the brachialis muscle was used as the expendable donor,
      and the recipients included the anterior interosseous nerve (AIN) (for volitional
      prehension), nerve branches to the flexor carpi radialis, and flexor digitorum
      superficialis. Two patients underwent additional nerve transfers: (1) supinator
      to extensor carpi ulnaris or (2) deltoid to triceps. No patients had any loss of
      baseline upper extremity function, seven of eight AIN nerve specimens had
      preserved micro-architecture, and all intraoperative stimulation of recipient
      neuromuscular units was successful further supporting feasibility. Four patients
      had perioperative complications; all resolved or improved (paresthesias).
      CONCLUSION: Nerve transfers can be used to reestablish volitional control of hand
      function in SCI. This surgery does not downgrade existing function, uses
      expendable donor nerve, and has no postoperative immobilization, which might make
      it a more viable option than traditional tendon transfer and other procedures.

PMID- 25767423
TI  - Alternatives to sural nerve grafts in the upper extremity.
AB  - BACKGROUND: The sural nerve is the most common nerve graft donor despite
      requiring a second operative limb and causing numbness of the lateral foot. The
      purposes of this study were to review our experience using nerve autografts in
      upper extremity nerve reconstruction and develop recommendations for donor
      selection. METHODS: A retrospective case series study was performed of all
      consecutive patients undergoing nerve grafting procedures for upper extremity
      nerve injuries over an 11-year period (2001-2012). RESULTS: Eighty-six patients
      received 109 nerve grafts over the study period. Mean patient age was 42.9 +/-
      18.3 years; 57 % were male. There were 51 median (59 %), 26 ulnar (30 %), 14
      digital (13 %), 13 radial (16 %), and 3 musculocutaneous (4 %) nerve injuries
      repaired with 99 nerve autografts (71 from upper extremity, 28 from lower
      extremity). Multiple upper extremity nerve autograft donors were utilized,
      including the medial antebrachial cutaneous nerve (MABC), third webspace branch
      of median, lateral antebrachial cutaneous nerve (LABC), palmar cutaneous, and
      dorsal cutaneous branch of ulnar nerve. By using an upper-extremity donor, a
      second operative limb was avoided in 58 patients (67 %), and a second incision
      was avoided in 26 patients (30 %). The frequency of sural graft use declined from
      40 % (n = 17/43) to 11 % (n = 7/64). CONCLUSIONS: Our algorithm for selecting
      nerve graft material has evolved with our growing understanding of nerve internal
      topography and the drive to minimize additional incisions, maximize ease of
      harvest, and limit donor morbidity. This has led us away from using the sural
      nerve when possible and allowed us to avoid a second operative limb in two thirds
      of the cases.

PMID- 25767424
TI  - Basal joint osteoarthritis of the thumb: comparison of suture button versus
      abductor pollicis longus suspensionplasty.
AB  - BACKGROUND: Our purpose was to compare the outcomes of patients with severe
      basilar thumb osteoarthritis treated with trapeziectomy and suspensionplasty
      using abductor pollicis longus (APL) tendon versus a suture button device.
      METHODS: A retrospective study was performed for patients undergoing
      trapeziectomy and suspensionplasty with APL tendon or suture button fixation.
      Outcome measures included disabilities of the arm, shoulder, and hand (DASH);
      visual analog score (VAS); grip strength; key pinch; tip pinch; and thumb
      opposition. Radiographic measurements, surgical times, and complications were
      recorded. RESULTS: Thirty-three patients in the APL tendon group and 27 patients
      in the suture button group had a minimum 6-month follow-up. VAS, DASH, and
      functional measurements improved after surgery for both groups. Mean operative
      time was 68 min for the APL tendon group and 48 min for the suture button group.
      Complications were similar between groups. CONCLUSIONS: The use of suture button
      fixation when compared to APL tendon suspensionplasty offers similar clinical
      outcomes. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic III.

PMID- 25767425
TI  - Dorsal fracture-dislocations of the proximal interphalangeal joint: evaluation of
      closed reduction and percutaneous Kirschner wire pinning.
AB  - BACKGROUND: The purpose of this study is to evaluate the outcome of closed
      reduction and percutaneous Kirschner wire pinning in acute dorsal fracture
      dislocations of the proximal interphalangeal (PIP) joint. METHODS: Eight men and
      one woman were treated with closed reduction and percutaneous Kirschner wire
      pinning by one orthopaedic surgeon. The ring finger was injured in six patients,
      the small finger in two patients and the middle finger in one patient. The mean
      joint surface involvement was 36 % (range, 26-49 %). The Kirschner wires were
      removed after an average of 28 days (range, 24-37 days). RESULTS: All patients
      demonstrated a painless, but fusiform, swollen PIP joint after a mean follow-up
      of 6.5 months. The average flexion of the PIP joint was 106 degrees  (range, 80
      110), and the average extension of the PIP joint was 4 degrees  short of full
      extension (range, 10 hyperextension-15 flexion contracture). All patients had a
      concentrically reduced PIP joint with a healed fracture on radiographs. Two
      patients had radiographic evidence of degenerative changes, but were
      asymptomatic. One patient developed a superficial pin track infection, which
      quickly resolved with a short course of antibiotics, and avascular necrosis
      affecting one of the condyles of the proximal phalanx. CONCLUSIONS: In agreement
      with previous studies, closed reduction and percutaneous Kirschner wire pinning
      in dorsal fracture-dislocations of the PIP joint is a minimally invasive and
      simple technique which appears to give satisfactory outcomes in the short to
      intermediate term.

PMID- 25767426
TI  - Biomechanical evaluation of metacarpal fracture fixation: application of a 90
      degrees  internal fixation model.
AB  - PURPOSE: Complications in metacarpal fracture treatment increase in proportion to
      the severity of the initial injury and the invasiveness of the surgical fixation
      technique. This manuscript evaluates the feasibility of minimizing internal
      fixation construct size and soft tissue dissection, while preserving the
      advantages of stable internal fixation in a biomechanical model. We hypothesized
      that comparable construct stability could be achieved with mini-plates in an
      orthogonal (90/90) configuration compared with a standard dorsal plating
      technique. METHODS: This hypothesis was evaluated in a transverse metacarpal
      fracture model. Twelve metacarpals were subject to either placement of a 2.0-mm
      six-hole dorsal plate or two 1.5-mm four-hole mini-plates in a 90/90
      configuration. These constructs were tested to failure in a three-point bending
      apparatus, attaining failure force, displacement, and stiffness. RESULTS: Mean
      failure force was 353.5 +/- 121.1 N for the dorsal plating construct and 358.8 +/
      77.1 N for the orthogonal construct. Mean failure displacement was 3.3 +/- 1.2
      mm for the dorsal plating construct and 4.1 +/- 0.9 mm for the orthogonal
      construct. Mean stiffness was 161.3 +/- 50.0 N/mm for the dorsal plating
      construct and 122.1 +/- 46.6 N/mm for the orthogonal construct. Mean failure
      moment was 3.09 +/- 1.06 Nm for the dorsal plating construct and 3.14 +/- 0.67 Nm
      for the orthogonal construct. The dorsal plating group failed via screw pullout,
      whereas the orthogonal failed either by screw pullout or breakage of the plate.
      CONCLUSIONS: When subject to apex dorsal bending, the orthogonal construct and
      the standard dorsal plate construct behaved comparably. These data suggest that
      despite its shorter length, lower profile, and less substantial screws, the
      orthogonal construct provides sufficient rigidity. CLINICAL RELEVANCE: This study
      represents a "proof of concept" regarding the applicability of orthogonal plating
      in the metacarpal and provides the foundation for minimizing construct size and
      profile.

PMID- 25767427
TI  - Dimensional analysis of the distal phalanx with consideration of distal
      interphalangeal joint arthrodesis using a headless compression screw.
AB  - BACKGROUND: Headless compression screws have been used for arthrodesis of the
      distal interphalangeal joint with good clinical results. However, some distal
      phalanges are too small, thus precluding their use, or increasing complication
      rates. METHODS: In order to validate our digital measurements, radiographs of
      five cadaveric hands were obtained. The distal phalanges of these fingers were
      measured using our institution's digital radiograph software. The cadavers were
      then dissected, and the actual phalanges were measured to confirm the accuracy of
      the digital measurements; 200 consecutive hand radiographs were then measured to
      obtain average width and heights of the narrowest measurements of the distal
      phalanx of each finger. Subgroup analysis of each finger for age and gender was
      completed. RESULTS AND CONCLUSIONS: Females were routinely smaller than their
      male counterparts. No age-related differences were seen. A substantial number of
      fingers were found to be too small to allow for use of headless compression
      screws; 42 % of small finger distal phalanges are too small to accommodate 2.8-mm
      threads, and that number increases to 81 % with 3.2-mm threads and 97 % with 3.5
      mm threads. Few distal phalanges, regardless of which finger, are large enough to
      accommodate 3.5-mm-diameter threads; 22% of female ring finger distal phalanges
      are smaller than 2.8 mm, and 66 % of ring fingers are smaller than 3.2 mm. Based
      on our measurements, a surprising number of distal phalanges are smaller than the
      trailing thread diameter of commonly commercially available headless screws. Care
      must be taken in selecting implants for distal interphalangeal (DIP) fusion.

PMID- 25767428
TI  - Effect of preservation of corticoperiosteal attachment on bone healing at
      osteotomy sites after ulna-shortening osteotomy.
AB  - BACKGROUND: Although precise ulna-shortening osteotomy is popular, the procedure
      sometimes results in delayed union or nonunion. The periosteum including the
      inner cambium layer plays an important role in fracture healing. We tested the
      hypothesis that preservation of the corticoperiosteal attachment may accelerate
      healing at osteotomy sites after ulna-shortening osteotomy. METHODS: We performed
      a chart review of 32 patients who underwent ulna-shortening osteotomy for ulnar
      impaction syndrome or triangular fibrocartilage complex tears in a retrospective
      single-surgeon series. Of the 32 cases, the periosteum was preserved in 21
      osteotomies performed from April 2009 onwards (periosteum-preserved group) and
      not preserved in 11 osteotomies performed before April 2009 (control group).
      Following sugar tong immobilization, patients in both groups used a short wrist
      supporter during the first two postoperative weeks (POW) and up to at least four
      POW. Union of the osteotomy site was assessed at 2-week intervals using
      radiographs taken at three different projections until 12 POW and at 4-week
      intervals thereafter until 24 POW. Ulna shortening was performed using a
      transverse osteotomy cut with the aid of a commercially available compression
      device. RESULTS: All osteotomies achieved complete union except in one case in
      the control group. The mean interval to complete cortical union was 7.7 weeks in
      the periosteum-preserved group and 9.5 weeks in the control group. The
      corresponding mean times for endosteal union were 15.6 and 21.8 weeks. The
      periosteum-preserved group had reduced times for both types of union but only the
      endosteal union time was significantly different from the control group.
      CONCLUSIONS: Preservation of the corticoperiosteal attachment significantly
      shortened the endosteal union time. Our results indicate that preservation of the
      periosteum may accelerate bone healing after ulna-shortening osteotomy.

PMID- 25767429
TI  - Phenolization and coralline hydroxyapatite grafting following meticulous
      curettage for the treatment of enchondroma of the hand. A case series of 82
      patients with 5-year follow-up.
AB  - BACKGROUND: Enchondromas are benign cartilaginous tumours. The most common
      location is in the long bones of the hand. Treatment methods fall into a broad
      spectrum ranging from conservative, medical therapies, to a variety of surgical
      procedures, which may or may not employ the use of local adjuvant treatment or
      bone grafting. The purpose of this study was to report our experience and
      evaluate the long-term results of patients with enchondroma of the hand, treated
      in our department with meticulous curettage, phenolization and coralline
      hydroxyapatite grafting. METHODS: We present 82 patients with hand enchondromas
      treated surgically in our department during the last 10 years. The patients were
      treated operatively with meticulous curettage of the bone lesion, with use of
      phenol 5 % as local adjuvant and coralline hydroxyapatite bone graft to fill in
      the remaining cavity. RESULTS: At a minimum of 5-year follow-up, radiographs and
      clinical examination showed adequate bone formation at the site of enchondroma
      excavation and no evidence of recurrence, fracture, infection or other
      complication related to the procedure. CONCLUSION: We concluded that the
      combination of meticulous curettage of the lesion, with the use of phenol as
      local adjuvant and coralline hydroxyapatite graft is a safe technique that
      prevents recurrence and allows adequate and uncomplicated local new bone
      formation.

PMID- 25767430
TI  - Implanted passive engineering mechanism improves hand function after tendon
      transfer surgery: a cadaver-based study.
AB  - PURPOSE: The purpose of this study was to investigate if a new tendon transfer
      surgical procedure that uses an implanted passive engineering mechanism for
      attaching multiple tendons to a single donor muscle in place of directly suturing
      the tendons to the muscle improves hand function in physical interaction tasks
      such as grasping. METHODS: The tendon transfer surgery for high median ulnar
      palsy was used as an exemplar, where all four flexor digitorum profundus (FDP)
      tendons are directly sutured to the extensor carpi radialis longus (ECRL) muscle
      to restore flexion. The new procedure used a passive hierarchical artificial
      pulley system to connect the muscle to the tendons. Both the suture-based and
      pulley-based procedures were conducted on N = 6 cadaver hands. The fingers'
      ability to close around four objects when the ECRL tendon was pulled was tested.
      Post-surgery hand function was evaluated based on the actuation force required to
      create a grasp and the slip between the fingers and the object after the grasp
      was created. RESULTS: When compared with the suture-based procedure, the pulley
      based procedure (i) reduced the actuation force required to close all four
      fingers around the object by 45 % and (ii) improved the fingers' individual
      adaptation to the object's shape during the grasping process and reduced slip by
      52 % after object contact (2.99 degrees  +/- 0.28 degrees  versus 6.22 degrees 
      +/- 0.66 degrees ). CONCLUSIONS: The cadaver study showed that the implanted
      engineering mechanism for attaching multiple tendons to one muscle significantly
      improved hand function in grasping tasks when compared with the current
      procedure.

PMID- 25767431
TI  - One-per-mil tumescent technique for bone and joint surgery in hand.
AB  - BACKGROUND: This study aims to explore the effectiveness of one-per-mil tumescent
      technique in hand surgery, which involves bone and joint. METHODS: This is a case
      series study on 14 patients with 15 operative fields. One-per-mil solution is
      formulated by mixing 0.05 mL of 1:1,000 epinephrine and 100 mg lidocaine in 50-mL
      saline solution. The solution was injected subcutaneously into the operative area
      until the skin turned pale. The surgery started 7-10 min after the last
      injection. We classified the operative field clarity into four categories:
      totally bloodless, minimum bleeding, acceptable bleeding, and bloody operative
      field. We also recorded the amount of tumescent solution, top-ups needed, length
      of surgery, type of anesthesia, and intraoperative pain reported by the patients
      under local anesthesia. RESULTS: Five patients were operated on under local
      anesthesia while the other ten were under general anesthesia. Eight cases yielded
      totally bloodless operative fields, while seven were classified as acceptable
      bleeding. There were no top-ups and conversion of anesthesia needed during
      surgery. CONCLUSIONS: We consider one-per-mil tumescent technique as a promising
      successor of pneumatic tourniquet in bone and joint surgery, especially for
      lengthy procedures on hand and upper extremity.

PMID- 25767432
TI  - The internet as a source of information for De Quervain's tendinitis.
AB  - BACKGROUND: Many individuals are turning to the Internet for information about
      various health conditions, and in our study we evaluated the quality and
      readability of information on the internet about De Quervain's tendinitis.
      METHODS: We chose the search terms "De Quervain's Tendinitis," "De Quervain's
      Tenosynovitis," and "De Quervain's Syndrome," and entered them into the search
      engines "Google," "Bing," and "Yahoo" and compiled the search results. The
      websites were then evaluated and assigned a quality score, a Flesch-Kincaid (FK)
      reading level, and a subjective quality score. They were then grouped according
      to the search term used, search engine used, and the order (priority) returned by
      the search engines. ANOVA analysis and pairwise comparisons of quality and
      readability among groups, as well as correlation analysis were performed.
      RESULTS: The FK readability average was 10.3, above the recommended level. The
      search term De Quervain's tenosynovitis returned the highest objective quality
      results. There was no statistical difference found between the different search
      engines. The first 10 results from the searches were of higher quality than
      results 11-20, and there was a positive correlation between objective and
      subjective quality scores but no correlation between readability and objective
      quality. CONCLUSIONS: We concluded that quality information about De Quervain's
      tendinitis is available on the internet and is most likely to be found using the
      search term De Quervain's tenosynovitis and in the first 10 results of an
      internet search. However, most information is written above the recommended 6th
      grade reading level.

PMID- 25767433
TI  - Workshop report: INCF short course on neuroinformatics, neurogenomics, and brain
      disease, 14-21 September 2013.

PMID- 25767434
TI  - Long-term depression is differentially expressed in distinct lamina of
      hippocampal CA1 dendrites.
AB  - Information storage in CA1 hippocampal pyramidal neurons is compartmentalized in
      proximal vs. distal apical dendrites, cell bodies, and basal dendrites. This
      compartmentalization is thought to be essential for synaptic integration.
      Differences in the expression of long-term potentiation (LTP) in each of these
      compartments have been described, but less is known regarding potential
      differences in long-term depression (LTD). Here, to directly compare LTD
      expression in each compartment and to bypass possible differences in input
      specificity and stimulation of presynaptic inputs, we used global application of
      NMDA to induce LTD. We then examined LTD expression in each dendritic sub-region
      proximal and distal apical, and basal dendrites-and in cell bodies.
      Interestingly, we found that distal apical dendrites exhibited the greatest
      magnitude of LTD of all areas tested and this LTD was maintained, whereas LTD in
      proximal apical dendrites was not maintained. In basal dendrites, LTD was also
      maintained, but the magnitude of LTD was less than in distal apical dendrites.
      Blockade of inhibition blocked LTD maintenance in both distal apical and basal
      dendrites. Population spikes recorded from the cell body layer correlated with
      apical dendrite field EPSP (fEPSP), where LTD was maintained in distal dendrites
      and decayed in proximal dendrites. On the other hand, LTD of basal dendrite
      fEPSPs was maintained but population spike responses were not. Thus E-S coupling
      was distinct in basal and apical dendrites. Our data demonstrate cell autonomous
      differential information processing in somas and dendritic sub-regions of CA1
      pyramidal neurons in the hippocampus, where LTD expression is intrinsic to
      distinct dendritic regions, and does not depend on the nature of stimulation and
      input specificity. 

PMID- 25767436
TI  - A chicken model for studying the emergence of invariant object recognition.
AB  - "Invariant object recognition" refers to the ability to recognize objects across
      variation in their appearance on the retina. This ability is central to visual
      perception, yet its developmental origins are poorly understood. Traditionally,
      nonhuman primates, rats, and pigeons have been the most commonly used animal
      models for studying invariant object recognition. Although these animals have
      many advantages as model systems, they are not well suited for studying the
      emergence of invariant object recognition in the newborn brain. Here, we argue
      that newly hatched chicks (Gallus gallus) are an ideal model system for studying
      the emergence of invariant object recognition. Using an automated controlled
      rearing approach, we show that chicks can build a viewpoint-invariant
      representation of the first object they see in their life. This invariant
      representation can be built from highly impoverished visual input (three images
      of an object separated by 15 degrees  azimuth rotations) and cannot be accounted
      for by low-level retina-like or V1-like neuronal representations. These results
      indicate that newborn neural circuits begin building invariant object
      representations at the onset of vision and argue for an increased focus on chicks
      as an animal model for studying invariant object recognition. 

PMID- 25767438
TI  - Emergence of spatially heterogeneous burst suppression in a neural field model of
      electrocortical activity.
AB  - Burst suppression in the electroencephalogram (EEG) is a well-described
      phenomenon that occurs during deep anesthesia, as well as in a variety of
      congenital and acquired brain insults. Classically it is thought of as spatially
      synchronous, quasi-periodic bursts of high amplitude EEG separated by low
      amplitude activity. However, its characterization as a "global brain state" has
      been challenged by recent results obtained with intracranial electrocortigraphy.
      Not only does it appear that burst suppression activity is highly asynchronous
      across cortex, but also that it may occur in isolated regions of circumscribed
      spatial extent. Here we outline a realistic neural field model for burst
      suppression by adding a slow process of synaptic resource depletion and recovery,
      which is able to reproduce qualitatively the empirically observed features during
      general anesthesia at the whole cortex level. Simulations reveal heterogeneous
      bursting over the model cortex and complex spatiotemporal dynamics during
      simulated anesthetic action, and provide forward predictions of neuroimaging
      signals for subsequent empirical comparisons and more detailed characterization.
      Because burst suppression corresponds to a dynamical end-point of brain activity,
      theoretically accounting for its spatiotemporal emergence will vitally contribute
      to efforts aimed at clarifying whether a common physiological trajectory is
      induced by the actions of general anesthetic agents. We have taken a first step
      in this direction by showing that a neural field model can qualitatively match
      recent experimental data that indicate spatial differentiation of burst
      suppression activity across cortex. 

PMID- 25767437
TI  - Ontogenesis of oxytocin pathways in the mammalian brain: late maturation and
      psychosocial disorders.
AB  - Oxytocin (OT), the main neuropeptide of sociality, is expressed in neurons
      exclusively localized in the hypothalamus. During the last decade, a plethora of
      neuroendocrine, metabolic, autonomic and behavioral effects of OT has been
      reported. In the urgency to find treatments to syndromes as invalidating as
      autism, many clinical trials have been launched in which OT is administered to
      patients, including adolescents and children. However, the impact of OT on the
      developing brain and in particular on the embryonic and early postnatal
      maturation of OT neurons, has been only poorly investigated. In the present
      review we summarize available (although limited) literature on general features
      of ontogenetic transformation of the OT system, including determination,
      migration and differentiation of OT neurons. Next, we discuss trajectories of OT
      receptors (OTR) in the perinatal period. Furthermore, we provide evidence that
      early alterations, from birth, in the central OT system lead to severe
      neurodevelopmental diseases such as feeding deficit in infancy and severe defects
      in social behavior in adulthood, as described in Prader-Willi syndrome (PWS). Our
      review intends to propose a hypothesis about developmental dynamics of central OT
      pathways, which are essential for survival right after birth and for the
      acquisition of social skills later on. A better understanding of the embryonic
      and early postnatal maturation of the OT system may lead to better OT-based
      treatments in PWS or autism. 

PMID- 25767435
TI  - Targeted pharmacological treatment of autism spectrum disorders: fragile X and
      Rett syndromes.
AB  - Autism spectrum disorders (ASDs) are genetically and clinically heterogeneous and
      lack effective medications to treat their core symptoms. Studies of syndromic
      ASDs caused by single gene mutations have provided insights into the
      pathophysiology of autism. Fragile X and Rett syndromes belong to the syndromic
      ASDs in which preclinical studies have identified rational targets for drug
      therapies focused on correcting underlying neural dysfunction. These preclinical
      discoveries are increasingly translating into exciting human clinical trials.
      Since there are significant molecular and neurobiological overlaps among ASDs,
      targeted treatments developed for fragile X and Rett syndromes may be helpful for
      autism of different etiologies. Here, we review the targeted pharmacological
      treatment of fragile X and Rett syndromes and discuss related issues in both
      preclinical studies and clinical trials of potential therapies for the diseases. 

PMID- 25767439
TI  - Dicholine succinate, the neuronal insulin sensitizer, normalizes behavior, REM
      sleep, hippocampal pGSK3 beta and mRNAs of NMDA receptor subunits in mouse models
      of depression.
AB  - Central insulin receptor-mediated signaling is attracting the growing attention
      of researchers because of rapidly accumulating evidence implicating it in the
      mechanisms of plasticity, stress response, and neuropsychiatric disorders
      including depression. Dicholine succinate (DS), a mitochondrial complex II
      substrate, was shown to enhance insulin-receptor mediated signaling in neurons
      and is regarded as a sensitizer of the neuronal insulin receptor. Compounds
      enhancing neuronal insulin receptor-mediated transmission exert an antidepressant
      like effect in several pre-clinical paradigms of depression; similarly, such
      properties for DS were found with a stress-induced anhedonia model. Here, we
      additionally studied the effects of DS on several variables which were
      ameliorated by other insulin receptor sensitizers in mice. Pre-treatment with DS
      of chronically stressed C57BL6 mice rescued normal contextual fear conditioning,
      hippocampal gene expression of NMDA receptor subunit NR2A, the NR2A/NR2B ratio
      and increased REM sleep rebound after acute predation. In 18-month-old C57BL6
      mice, a model of elderly depression, DS restored normal sucrose preference and
      activated the expression of neural plasticity factors in the hippocampus as shown
      by Illumina microarray. Finally, young naive DS-treated C57BL6 mice had reduced
      depressive- and anxiety-like behaviors and, similarly to imipramine-treated mice,
      preserved hippocampal levels of the phosphorylated (inactive) form of GSK3 beta
      that was lowered by forced swimming in pharmacologically naive animals. Thus, DS
      can ameliorate behavioral and molecular outcomes under a variety of stress- and
      depression-related conditions. This further highlights neuronal insulin signaling
      as a new factor of pathogenesis and a potential pharmacotherapy of affective
      pathologies. 

PMID- 25767441
TI  - Propensity to obesity impacts the neuronal response to energy imbalance.
AB  - The mechanisms responsible for the propensity to gain weight or remain normal
      weight are poorly understood. The objective of this study was to study the
      neuronal response to visual food cues during short-term energy imbalance in
      healthy adults recruited as obesity-resistant (OR) or obesity-prone (OP) based on
      self-identification, body mass index, and personal/family weight history. Twenty
      five OR and 28 OP subjects were studied in underfed (UF) and overfed (OF) as
      compared to eucaloric (EU) conditions in a randomized crossover design. Each
      study phase included a 3-day run-in diet, 1 day of controlled feeding (basal
      energy needs for EU, 40% above/below basal energy needs for OF/UF), and a test
      day. On the test day, fMRI was performed in the acute fed stated (30 min after a
      test meal) while subjects viewed images of foods of high hedonic value and
      neutral non-food objects. Measures of appetite and hormones were also performed
      before and every 30 min after the test meal. UF was associated with significantly
      increased activation of insula, somatosensory cortex, inferior and medial
      prefrontal cortex (PFC), parahippocampus, precuneus, cingulate, and visual cortex
      in OR. However, UF had no impact in OP. As a result, UF was associated with
      significantly greater activation, specifically in the insula, inferior PFC, and
      somatosensory cortex in OR as compared to OP. While OF was overall associated
      with reduced activation of inferior visual cortex, no group interaction was
      observed with OF. In summary, these findings suggest that individuals resistant
      to weight gain and obesity are more sensitive to short-term energy imbalance,
      particularly with UF, than those prone to weight gain. The inability to sense or
      adapt to changes in energy balance may represent an important mechanism
      contributing to excess energy intake and risk for obesity. 

PMID- 25767440
TI  - Social behavioral changes in MPTP-treated monkey model of Parkinson's disease.
AB  - Parkinsonian patients experience not only the physical discomfort of motor
      disorders but also the considerable psychological distress caused by cognitive
      deficits and behavioral disorders. These two factors can result in a disruption
      of social relationships during the symptomatic and even the presymptomatic motor
      states of the disease. However, it remains difficult, if not impossible, to
      evaluate social relationships in presymptomatic patients. The present study
      focused on the evaluation of social relationships within a group of female long
      tailed macaques during presymptomatic and symptomatic motor states induced by
      Chronic Low-Dose (CLD) and then Chronic High-Dose (CHD) systemic administration
      of 1-methyl-4-phenyl-l,2,3,6-tetrahydropyridine (MPTP). Dopaminergic denervation
      within basal ganglia and cortical areas was evaluated using Positron Emission
      Tomography (PET) scans with (18)F-DOPA (6-[18F]-fluoro-L-3,4
      dihydroxyphenylalanine) radiotracer. Interestingly, social behavioral changes
      could be identified in the presymptomatic motor state before any motor and/or
      cognitive impairment occurred. Stronger effects were observed in subordinate
      animals compared to dominant animals. From baseline state to CLD-presymptomatic
      motor state, the frequency of emitted affiliative and aggressive behaviors
      increased. From CLD-presymptomatic to CHD-presymptomatic motor states, the
      frequency of the three categories of social behaviors (aggressive, submissive and
      affiliative) decreased. At this time, quantitative data analysis in PET scans
      highlighted a dopaminergic denervation in the insula and the posterior caudate
      nucleus. Finally, the frequency of the three categories of social behaviors
      decreased during the stable-symptomatic motor state compared to baseline and
      presymptomatic motor states; this was also associated with motor and cognitive
      disorders and a dopaminergic denervation in all the evaluated cortical and
      subcortical structures. 

PMID- 25767442
TI  - Take a stand on understanding: electrophysiological evidence for stem access in
      German complex verbs.
AB  - The lexical representation of complex words in Indo-European languages is
      generally assumed to depend on semantic compositionality. This study investigated
      whether semantically compositional and noncompositional derivations are accessed
      via their constituent units or as whole words. In an overt visual priming
      experiment (300 ms stimulus onset asynchrony, SOA), event-related potentials
      (ERPs) were recorded for verbs (e.g., ziehen, "pull") that were preceded by
      purely semantically related verbs (e.g., zerren, "drag"), by morphologically
      related and semantically compositional verbs (e.g., zuziehen, "pull together"),
      by morphologically related and semantically noncompositional verbs (e.g.,
      erziehen, "educate"), by orthographically similar verbs (e.g., zielen, "aim"), or
      by unrelated verbs (e.g., tarnen, "mask"). Compared to the unrelated condition,
      which evoked an N400 effect with the largest amplitude at centro-parietal
      recording sites, the N400 was reduced in all other conditions. The rank order of
      N400 amplitudes turned out as follows: morphologically related and semantically
      compositional ~ morphologically related and semantically noncompositional <
      purely semantically related < orthographically similar < unrelated. Surprisingly,
      morphologically related primes produced similar N400 modulations-irrespective of
      their semantic compositionality. The control conditions with orthographic
      similarity confirmed that these morphological effects were not the result of a
      simple form overlap between primes and targets. Our findings suggest that the
      lexical representation of German complex verbs refers to their base form,
      regardless of meaning compositionality. Theories of the lexical representation of
      German words need to incorporate this aspect of language processing in German. 

PMID- 25767443
TI  - Brain activations during bimodal dual tasks depend on the nature and combination
      of component tasks.
AB  - We used functional magnetic resonance imaging to investigate brain activations
      during nine different dual tasks in which the participants were required to
      simultaneously attend to concurrent streams of spoken syllables and written
      letters. They performed a phonological, spatial or "simple" (speaker-gender or
      font-shade) discrimination task within each modality. We expected to find
      activations associated specifically with dual tasking especially in the frontal
      and parietal cortices. However, no brain areas showed systematic dual task
      enhancements common for all dual tasks. Further analysis revealed that dual tasks
      including component tasks that were according to Baddeley's model "modality
      atypical," that is, the auditory spatial task or the visual phonological task,
      were not associated with enhanced frontal activity. In contrast, for other dual
      tasks, activity specifically associated with dual tasking was found in the left
      or bilateral frontal cortices. Enhanced activation in parietal areas, however,
      appeared not to be specifically associated with dual tasking per se, but rather
      with intermodal attention switching. We also expected effects of dual tasking in
      left frontal supramodal phonological processing areas when both component tasks
      required phonological processing and in right parietal supramodal spatial
      processing areas when both tasks required spatial processing. However, no such
      effects were found during these dual tasks compared with their component tasks
      performed separately. Taken together, the current results indicate that
      activations during dual tasks depend in a complex manner on specific demands of
      component tasks. 

PMID- 25767444
TI  - Changes in EEG complexity with electroconvulsive therapy in a patient with autism
      spectrum disorders: a multiscale entropy approach.
AB  - Autism spectrum disorders (ASD) are heterogeneous neurodevelopmental disorders
      that are reportedly characterized by aberrant neural networks. Recently developed
      multiscale entropy analysis (MSE) can characterize the complexity inherent in
      electroencephalography (EEG) dynamics over multiple temporal scales in the
      dynamics of neural networks. We encountered an 18-year-old man with ASD whose
      refractory catatonic obsessive-compulsive symptoms were improved dramatically
      after electroconvulsive therapy (ECT). In this clinical case study, we strove to
      clarify the neurophysiological mechanism of ECT in ASD by assessing EEG
      complexity using MSE. Along with ECT, the frontocentral region showed decreased
      EEG complexity at higher temporal scales, whereas the occipital region expressed
      an increase at lower temporal scales. Furthermore, these changes were associated
      with clinical improvement associated with the elevation of brain-derived
      neurotrophic factor, which is a molecular hypothesis of ECT, playing key roles in
      ASD pathogenesis. Changes in EEG complexity in a region-specific and temporal
      scale-specific manner that we found might reflect atypical EEG dynamics in ASD.
      Although MSE is not a direct approach to measuring neural connectivity and the
      results are from only a single case, they might reflect specific aberrant neural
      network activity and the therapeutic neurophysiological mechanism of ECT in ASD. 

PMID- 25767446
TI  - Phase-dependent modulation as a novel approach for therapeutic brain stimulation.
AB  - Closed-loop paradigms provide us with the opportunity to optimize stimulation
      protocols for perturbation of pathological oscillatory activity in brain-related
      disorders. In this vein, spiking activity of motor cortex neurons and beta
      activity of local field potentials in the subthalamic nucleus have both been used
      independently of each other as neuronal signals to trigger deep brain stimulation
      for alleviating Parkinsonism. These approaches were superior to the standard
      continuous high-frequency stimulation protocols used in daily practice. However,
      they achieved their effects by bursts of stimulation that were applied at high
      frequency as well, i.e., independent of the phase information in the stimulated
      region. In this context, we propose that, by timing stimulation pulses relative
      to the ongoing oscillation, an alternative approach, namely the targeted
      perturbation of pathological rhythms, could be obtained. In this modeling study,
      we first captured the underlying dynamics of neuronal oscillations in the human
      subthalamic nucleus by phased coupled neuronal oscillators. We then quantified
      the nature of the interaction between these coupled oscillators by obtaining a
      physiologically informed phase response curve from local field potentials.
      Reconstruction of the phase response curve predicted the sensitivity of the phase
      oscillator to external stimuli, revealing phase intervals that optimally
      maximized the degree of perturbation. We conclude that our specifically timed
      intervention based on the coupled oscillator concept will enable us to identify
      personalized ways of delivering stimulation pulses in closed-loop paradigms
      triggered by the phase of pathological oscillations. This will pave the way for
      novel physiological insights and substantial clinical benefits. In addition, this
      precisely phased modulation may be capable of modifying the effective
      interactions between oscillators in an entirely new manner. 

PMID- 25767447
TI  - Decoding of human hand actions to handle missing limbs in neuroprosthetics.
AB  - The only way we can interact with the world is through movements, and our primary
      interactions are via the hands, thus any loss of hand function has immediate
      impact on our quality of life. However, to date it has not been systematically
      assessed how coordination in the hand's joints affects every day actions. This is
      important for two fundamental reasons. Firstly, to understand the representations
      and computations underlying motor control "in-the-wild" situations, and secondly
      to develop smarter controllers for prosthetic hands that have the same
      functionality as natural limbs. In this work we exploit the correlation structure
      of our hand and finger movements in daily-life. The novelty of our idea is that
      instead of averaging variability out, we take the view that the structure of
      variability may contain valuable information about the task being performed. We
      asked seven subjects to interact in 17 daily-life situations, and quantified
      behavior in a principled manner using CyberGlove body sensor networks that, after
      accurate calibration, track all major joints of the hand. Our key findings are:
      (1) We confirmed that hand control in daily-life tasks is very low-dimensional,
      with four to five dimensions being sufficient to explain 80-90% of the
      variability in the natural movement data. (2) We established a universally
      applicable measure of manipulative complexity that allowed us to measure and
      compare limb movements across tasks. We used Bayesian latent variable models to
      model the low-dimensional structure of finger joint angles in natural actions.
      (3) This allowed us to build a naive classifier that within the first 1000 ms of
      action initiation (from a flat hand start configuration) predicted which of the
      17 actions was going to be executed-enabling us to reliably predict the action
      intention from very short-time-scale initial data, further revealing the
      foreseeable nature of hand movements for control of neuroprosthetics and tele
      operation purposes. (4) Using the Expectation-Maximization algorithm on our
      latent variable model permitted us to reconstruct with high accuracy (<5-6
      degrees  MAE) the movement trajectory of missing fingers by simply tracking the
      remaining fingers. Overall, our results suggest the hypothesis that specific hand
      actions are orchestrated by the brain in such a way that in the natural tasks of
      daily-life there is sufficient redundancy and predictability to be directly
      exploitable for neuroprosthetics. 

PMID- 25767448
TI  - Coordination of dendritic inhibition through local disinhibitory circuits.
AB  - It has been recognized for some time that different subtypes of cortical
      inhibitory interneurons innervate specific dendritic domains of principal cells
      and release GABA at particular times during behaviorally relevant network
      oscillations. However, the lack of basic information on how the activity of
      interneurons can be controlled by GABA released in particular behavioral states
      has hindered our understanding of the rules that govern the spatio-temporal
      organization and function of dendritic inhibition. Similar to principal cells,
      any given interneuron may receive several functionally distinct inhibitory inputs
      that target its specific subcellular domains. We recently found that local
      circuitry of the so-called interneuron-specific (IS) interneurons is responsible
      for dendritic inhibition of different subtypes of hippocampal interneurons with a
      great impact on cell output. Here, we will review the properties and the
      specificity of connections of IS interneurons in the CA1 hippocampus and
      neocortex, and discuss their possible role in the activity-dependent regulation
      of dendritic inhibition received by pyramidal neurons. 

PMID- 25767445
TI  - State-dependencies of learning across brain scales.
AB  - Learning is a complex brain function operating on different time scales, from
      milliseconds to years, which induces enduring changes in brain dynamics. The
      brain also undergoes continuous "spontaneous" shifts in states, which, amongst
      others, are characterized by rhythmic activity of various frequencies. Besides
      the most obvious distinct modes of waking and sleep, wake-associated brain states
      comprise modulations of vigilance and attention. Recent findings show that
      certain brain states, particularly during sleep, are essential for learning and
      memory consolidation. Oscillatory activity plays a crucial role on several
      spatial scales, for example in plasticity at a synaptic level or in communication
      across brain areas. However, the underlying mechanisms and computational rules
      linking brain states and rhythms to learning, though relevant for our
      understanding of brain function and therapeutic approaches in brain disease, have
      not yet been elucidated. Here we review known mechanisms of how brain states
      mediate and modulate learning by their characteristic rhythmic signatures. To
      understand the critical interplay between brain states, brain rhythms, and
      learning processes, a wide range of experimental and theoretical work in animal
      models and human subjects from the single synapse to the large-scale cortical
      level needs to be integrated. By discussing results from experiments and
      theoretical approaches, we illuminate new avenues for utilizing neuronal learning
      mechanisms in developing tools and therapies, e.g., for stroke patients and to
      devise memory enhancement strategies for the elderly. 

PMID- 25767449
TI  - Aberrant Functional Connectivity in the Default Mode and Central Executive
      Networks in Subjects with Schizophrenia - A Whole-Brain Resting-State ICA Study.
AB  - Neurophysiological changes of schizophrenia are currently linked to disturbances
      in connectivity between functional brain networks. Functional magnetic resonance
      imaging studies on schizophrenia have focused on a few selected networks. Also
      previously, it has not been possible to discern whether the functional
      alterations in schizophrenia originate from spatial shifting or amplitude
      alterations of functional connectivity. In this study, we aim to discern the
      differences in schizophrenia patients with respect to spatial shifting vs. signal
      amplitude changes in functional connectivity in the whole-brain connectome. We
      used high model order-independent component analysis to study some 40 resting
      state networks (RSN) covering the whole cortex. Group differences were analyzed
      with dual regression coupled with y-concat correction for multiple comparisons.
      We investigated the RSNs with and without variance normalization in order to
      discern spatial shifting from signal amplitude changes in 43 schizophrenia
      patients and matched controls from the Northern Finland 1966 Birth Cohort. Voxel
      level correction for multiple comparisons revealed 18 RSNs with altered
      functional connectivity, 6 of which had both spatial and signal amplitude
      changes. After adding the multiple comparison, y-concat correction to the
      analysis for including the 40 RSNs as well, we found that four RSNs showed still
      changes. These robust changes actually seem encompass parcellations of the
      default mode network and central executive networks. These networks both have
      spatially shifted connectivity and abnormal signal amplitudes. Interestingly the
      networks seem to mix their functional representations in areas like left caudate
      nucleus and dorsolateral prefrontal cortex. These changes overlapped with areas
      that have been related to dopaminergic alterations in patients with schizophrenia
      compared to controls. 

PMID- 25767450
TI  - Circuit to construct mapping: a mathematical tool for assisting the diagnosis and
      treatment in major depressive disorder.
AB  - Major depressive disorder (MDD) is a serious condition with a lifetime prevalence
      exceeding 16% worldwide. MDD is a heterogeneous disorder that involves multiple
      behavioral symptoms on the one hand and multiple neuronal circuits on the other
      hand. In this review, we integrate the literature on cognitive and physiological
      biomarkers of MDD with the insights derived from mathematical models of brain
      networks, especially models that can be used for fMRI datasets. We refer to the
      recent NIH research domain criteria initiative, in which a concept of
      "constructs" as functional units of mental disorders is introduced. Constructs
      are biomarkers present at multiple levels of brain functioning - cognition,
      genetics, brain anatomy, and neurophysiology. In this review, we propose a new
      approach which we called circuit to construct mapping (CCM), which aims to
      characterize causal relations between the underlying network dynamics (as the
      cause) and the constructs referring to the clinical symptoms of MDD (as the
      effect). CCM involves extracting diagnostic categories from behavioral data,
      linking circuits that are causal to these categories with use of clinical
      neuroimaging data, and modeling the dynamics of the emerging circuits with
      attractor dynamics in order to provide new, neuroimaging-related biomarkers for
      MDD. The CCM approach optimizes the clinical diagnosis and patient
      stratification. It also addresses the recent demand for linking circuits to
      behavior, and provides a new insight into clinical treatment by investigating the
      dynamics of neuronal circuits underneath cognitive dimensions of MDD. CCM can
      serve as a new regime toward personalized medicine, assisting the diagnosis and
      treatment of MDD. 

PMID- 25767451
TI  - Balanced bilingualism and early age of second language acquisition as the
      underlying mechanisms of a bilingual executive control advantage: why variations
      in bilingual experiences matter.
AB  - Recent studies revealed inconsistent evidences of a bilingual advantage in
      executive processing. One potential source of explanation is the multifaceted
      experience of the bilinguals in these studies. This study seeks to test whether
      bilinguals who engage in language selection more frequently would perform better
      in executive control tasks than those bilinguals who engage in language selection
      less frequently. We examined the influence of the degree of bilingualism (i.e.,
      language proficiency, frequency of use of two languages, and age of second
      language acquisition) on executive functioning in bilingual young adults using a
      comprehensive battery of executive control tasks. Seventy-two 18- to 25-years-old
      English-Mandarin bilinguals performed four computerized executive function (EF)
      tasks (Stroop, Eriksen flanker, number-letter switching, and n-back task) that
      measure the EF components: inhibition, mental-set shifting, and information
      updating and monitoring. Results from multiple regression analyses, structural
      equation modeling, and bootstrapping supported the positive association between
      age of second language acquisition and the interference cost in the Stroop task.
      Most importantly, we found a significant effect of balanced bilingualism
      (balanced usage of and balanced proficiency in two languages) on the Stroop and
      number-letter task (mixing cost only), indicating that a more balanced use and a
      more balanced level of proficiency in two languages resulted in better executive
      control skills in the adult bilinguals. We did not find any significant effect of
      bilingualism on flanker or n-back task. These findings provided important
      insights to the underlying mechanisms of the bilingual cognitive advantage
      hypothesis, demonstrating that regular experience with extensive practice in
      controlling attention to their two language systems results in better performance
      in related EFs such as inhibiting prepotent responses and global set-shifting. 

PMID- 25767452
TI  - The relationships of character strengths with coping, work-related stress, and
      job satisfaction.
AB  - Personality traits have often been highlighted to relate to how people cope with
      stressful events. The present paper focuses on character strengths as positive
      personality traits and examines two basic assumptions that were derived from a
      core characteristic of character strengths (i.e., to determine how individuals
      deal with adversities): (1) character strengths correlate with coping and (2)
      buffer the effects of work-related stress on job satisfaction. Two different
      samples (i.e., a mixed sample representing various occupations [N = 214] and a
      nurses sample [N = 175]) filled in measures for character strengths, coping, work
      related stress, and job satisfaction. As expected, intellectual, emotional, and
      interpersonal strengths were related to coping. Interpersonal strengths played a
      greater role for coping among nurses, as interactions with others are an
      essential part of their workday. Furthermore, intellectual strengths partially
      mediated the negative effect of work-related stress on job satisfaction. These
      findings open a new field for research on the role of personality in coping with
      work-related stress. Character strengths are trainable personal characteristics,
      and therefore valuable resources to improve coping with work-related stress and
      to decrease the negative effects of stress. Further research is needed to
      investigate this assumed causality. 

PMID- 25767453
TI  - The influence of negative stimulus features on conflict adaption: evidence from
      fluency of processing.
AB  - Cognitive control enables adaptive behavior in a dynamically changing
      environment. In this context, one prominent adaptation effect is the sequential
      conflict adjustment, i.e., the observation of reduced response interference on
      trials following conflict trials. Increasing evidence suggests that such response
      conflicts are registered as aversive signals. So far, however, the functional
      role of this aversive signal for conflict adaptation to occur has not been put to
      test directly. In two experiments, the affective valence of conflict stimuli was
      manipulated by fluency of processing (stimulus contrast). Experiment 1 used a
      flanker interference task, Experiment 2 a color-word Stroop task. In both
      experiments, conflict adaptation effects were only present in fluent, but absent
      in disfluent trials. Results thus speak against the simple idea that any aversive
      stimulus feature is suited to promote specific conflict adjustments. Two
      alternative but not mutually exclusive accounts, namely resource competition and
      adaptation-by-motivation, will be discussed. 

PMID- 25767455
TI  - Parsing (malicious) pleasures: schadenfreude and gloating at others' adversity.
AB  - We offer the first empirical comparison of the pleasure in seeing (i.e.,
      schadenfreude) and in causing (i.e., gloating) others' adversity. In Study 1, we
      asked participants to recall and report on an (individual or group) episode of
      pleasure that conformed to our formal definition of schadenfreude, gloating,
      pride, or joy, without reference to an emotion word. Schadenfreude and gloating
      were distinct in the situational features of the episode, participants'
      appraisals of it, and their expressions of pleasure (e.g., smiling, boasting). In
      Study 2, we had participants imagine being in an (individual or group) emotion
      episode designed to fit our conceptualization of schadenfreude or gloating.
      Individual and group versions of the emotions did not differ much in either
      study. However, the two pleasures differed greatly in their situational features,
      appraisals, experience, and expression. This parsing of the particular pleasures
      of schadenfreude and gloating brings nuance to the study of (malicious) pleasure,
      which tends to be less finely conceptualized and examined than displeasure
      despite its importance to social relations. 

PMID- 25767454
TI  - The association between imitation recognition and socio-communicative
      competencies in chimpanzees (Pan troglodytes).
AB  - Imitation recognition provides a viable platform from which advanced social
      cognitive skills may develop. Despite evidence that non-human primates are
      capable of imitation recognition, how this ability is related to social cognitive
      skills is unknown. In this study, we compared imitation recognition performance,
      as indicated by the production of testing behaviors, with performance on a series
      of tasks that assess social and physical cognition in 49 chimpanzees. In the
      initial analyses, we found that males were more responsive than females to being
      imitated and engaged in significantly greater behavior repetitions and testing
      sequences. We also found that subjects who consistently recognized being imitated
      performed better on social but not physical cognitive tasks, as measured by the
      Primate Cognitive Test Battery. These findings suggest that the neural constructs
      underlying imitation recognition are likely associated with or among those
      underlying more general socio-communicative abilities in chimpanzees.
      Implications regarding how imitation recognition may facilitate other social
      cognitive processes, such as mirror self-recognition, are discussed. 

PMID- 25767456
TI  - Linguistic influence on mathematical development is specific rather than
      pervasive: revisiting the Chinese Number Advantage in Chinese and English
      children.
AB  - The relative linguistic transparency of the Asian counting system has been used
      to explain Asian students' relative superiority in cross-cultural comparisons of
      mathematics achievement. To test the validity and extent of linguistic
      transparency in accounting for mathematical abilities, this study tested Chinese
      and British primary school children. Children in Hong Kong can learn mathematics
      using languages with both regular (Chinese) and irregular (English) counting
      systems, depending on their schools' medium of instruction. This makes it
      possible to compare groups with varying levels of exposure to the regular and
      irregular number systems within the same educational system, curriculum, and
      cultural environment. The study included three groups of first/second graders and
      third/fourth graders with varying degrees of experience to the Chinese language
      and counting systems: no experience (UK; n = 49); spoke Chinese at home and
      learnt to count in English at school (HK-E; n = 43); spoke Chinese at home and
      learnt to count in Chinese at school (HK-C; n = 47). They were compared on
      counting, numerical abilities and place value representation. The present study
      also measured nonverbal reasoning, attitude toward mathematics, involvement of
      parents, and extra-curricular mathematics lessons to explore alternative
      explanations of children's numeric ability. Results indicated that students in HK
      C were better at counting backward and on the numeric skills test than those in
      HK-E, who were in turn better than the UK students. However, there was no
      statistical difference in counting forward, place value understanding, and a
      measure of arithmetic. Our findings add to existent literature suggesting that
      linguistic transparency does not have an all-pervasive influence on cross
      national differences in arithmetic performance. 

PMID- 25767457
TI  - Are past and future symmetric in mental time line?
AB  - A growing body of evidence has suggested that time, from early to late, or from
      past to future, was represented in a spatially oriented mental time line.
      However, little is known about its characteristics. The present study provided
      the first empirical evidence to explore the symmetry of spatial representations
      of past and future in the mental time line. Specifically, we compared the Spatial
      Temporal Association Response Codes (STARC) effects and distance effects of past
      and future in four experiments. Results showed that for near past and near
      future, STARC effects were similar (Experiment 1). For distant past, the STARC
      effect was significant, but not for distant future (Experiment 2). Furthermore,
      the distance effect in the past was significantly stronger than in the future
      (Experiments 3, 4). These findings supported the idea that time points are not
      evenly distributed in mental time line. Spatial representations of the past and
      the future are asymmetric, and the spatial representation of past seems stronger
      than future. The logarithmic pattern of internal spatial representation of past
      or future is also discussed. 

PMID- 25767458
TI  - Rethinking the role of sham TMS.
AB  - Sham transcranial magnetic stimulation (TMS) approaches are widely used in basic
      and clinical research to ensure that observed effects are due to the intended
      neural manipulation instead of being caused by various possible side effects. We
      here critically discuss several methodological aspects of sham TMS. Importantly,
      we propose to carefully distinguish between the placebo versus sensory side
      effects of TMS. In line with this conceptual distinction, we describe current
      limitations of sham TMS approaches in the context of placebo effects and blinding
      success, followed by a short review of our own work demonstrating that the
      sensory side effects of sham TMS are not unspecific as often falsely assumed.
      Lastly, we argue that sham TMS approaches are inherently insufficient as full
      fledged control conditions as they fail to demonstrate the specificity of TMS
      effects to a particular brain area or time point of stimulation. Sham TMS should
      therefore only complement alternative control strategies in TMS research. 

PMID- 25767459
TI  - Short-term meditation increases blood flow in anterior cingulate cortex and
      insula.
AB  - Asymmetry in frontal electrical activity has been reported to be associated with
      positive mood. One form of mindfulness meditation, integrative body-mind training
      (IBMT) improves positive mood and neuroplasticity. The purpose of this study is
      to determine whether short-term IBMT improves mood and induces frontal asymmetry.
      This study showed that 5-days (30-min per day) IBMT significantly enhanced
      cerebral blood flow (CBF) in subgenual/adjacent ventral anterior cingulate cortex
      (ACC), medial prefrontal cortex and insula. The results showed that both IBMT and
      relaxation training increased left laterality of CBF, but only IBMT improved CBF
      in left ACC and insula, critical brain areas in self-regulation. 

PMID- 25767460
TI  - Elevated romantic love and jealousy if relationship status is declared on
      Facebook.
AB  - Declared relationship status on Facebook can serve as a public commitment and as
      an extra layer of a couple's security. However, the question arises: do those who
      report the relationship status feel stronger romantic love and jealousy toward
      their partners than those who do not share such information publicly? To test
      this assumption, profile information and questionnaire data of romantic love and
      jealousy were gathered from 292, 230 females) respondents that were in a
      relationship. Our results suggest that announcing the relationship status is
      associated with elevated romantic love and jealousy. Therefore, being "Facebook
      official" can be interpreted as a tie-sign indicating that the couple is "out of
      the market," and can promote their unity as a "digital wedding ring." 

PMID- 25767461
TI  - A Framework for Quantitative Modeling of Neural Circuits Involved in Sleep-to
      Wake Transition.
AB  - Identifying the neuronal circuits and dynamics of sleep-to-wake transition is
      essential to understanding brain regulation of behavioral states, including sleep
      wake cycles, arousal, and hyperarousal. Recent work by different laboratories has
      used optogenetics to determine the role of individual neuromodulators in state
      transitions. The optogenetically driven data do not yet provide a multi
      dimensional schematic of the mechanisms underlying changes in vigilance states.
      This work presents a modeling framework to interpret, assist, and drive research
      on the sleep-regulatory network. We identify feedback, redundancy, and gating
      hierarchy as three fundamental aspects of this model. The presented model is
      expected to expand as additional data on the contribution of each transmitter to
      a vigilance state becomes available. Incorporation of conductance-based models of
      neuronal ensembles into this model and existing models of cortical excitability
      will provide more comprehensive insight into sleep dynamics as well as sleep and
      arousal-related disorders. 

PMID- 25767462
TI  - Digital Health Revolution: Is it Time for Affordable Remote Monitoring for
      Parkinson's Disease?

PMID- 25767464
TI  - Identification of essential amino acid residues in the nisin dehydratase NisB.
AB  - Nisin is a posttranslationally-modified antimicrobial peptide that has the
      ability to induce its own biosynthesis. Serines and threonines in the modifiable
      core peptide part of precursor nisin are dehydrated to dehydroalanines and
      dehydrobutyrines by the dehydratase NisB, and subsequently cysteines are coupled
      to the dehydroamino acids by the cyclase NisC. In this study, we applied
      extensive site-directed mutagenesis, together with direct binding studies, to
      investigate the molecular mechanism of the dehydratase NisB. We use a natural
      nisin-producing strain as a host to probe mutant-NisB functionality. Importantly,
      we are able to differentiate between intracellular and secreted fully dehydrated
      precursor nisin, enabling investigation of the NisB properties needed for the
      release of dehydrated precursor nisin to its devoted secretion system NisT. We
      report that single amino acid substitutions of conserved residues, i.e., R83A,
      R83M, and R87A result in incomplete dehydration of precursor nisin and prevention
      of secretion. Single point NisB mutants Y80F and H961A, result in a complete lack
      of dehydration of precursor nisin, but do not abrogate precursor nisin binding.
      The data indicate that residues Y80 and H961 are directly involved in catalysis,
      fitting well with their position in the recently published 3D-structure of NisB.
      We confirm, by in vivo studies, results that were previously obtained from in
      vitro experiments and NisB structure elucidation and show that previous findings
      translate well to effects seen in the original production host. 

PMID- 25767463
TI  - Structure-function relationships of glycoprotein hormones and their subunits'
      ancestors.
AB  - Glycoprotein hormones (GPHs) are the most complex molecules with hormonal
      activity. They exist only in vertebrates but the genes encoding their subunits'
      ancestors are found in most vertebrate and invertebrate species although their
      roles are still unknown. In the present report, we review the available
      structural and functional data concerning GPHs and their subunits' ancestors. 

PMID- 25767465
TI  - Exploration of Aspergillus fumigatus Ras pathways for novel antifungal drug
      targets.
AB  - Ras pathway signaling is a critical virulence determinant for pathogenic fungi.
      Localization of Ras to the plasma membrane (PM) is required for Ras network
      interactions supporting fungal growth and virulence. For example, loss of
      Aspergillus fumigatus RasA signaling at the PM via inhibition of palmitoylation
      leads to decreased growth, altered hyphal morphogenesis, decreased cell wall
      integrity and loss of virulence. In order to be properly localized and activated,
      Ras proteins must transit a series of post-translational modification (PTM)
      steps. These steps include farnesylation, proteolytic cleavage of terminal amino
      acids, carboxymethylation, and palmitoylation. Because Ras activation drives
      tumor development, Ras pathways have been extensively studied in mammalian cells
      as a potential target for anti-cancer therapy. Inhibitors of mammalian Ras
      interactions and PTM components have been, or are actively being, developed. This
      review will focus on the potential for building upon existing scaffolds to
      exploit fungal Ras proteins for therapy, synthesizing data from studies employing
      both mammalian and fungal systems. 

PMID- 25767466
TI  - Spatial distribution of bacterial communities driven by multiple environmental
      factors in a beach wetland of the largest freshwater lake in China.
AB  - The spatial distributions of bacterial communities may be driven by multiple
      environmental factors. Thus, understanding the relationships between bacterial
      distribution and environmental factors is critical for understanding wetland
      stability and the functioning of freshwater lakes. However, little research on
      the bacterial communities in deep sediment layers exists. In this study, thirty
      clone libraries of 16S rRNA were constructed from a beach wetland of the Poyang
      Lake along both horizontal (distance to the water-land junction) and vertical
      (sediment depth) gradients to assess the effects of sediment properties on
      bacterial community structure and diversity. Our results showed that bacterial
      diversity increased along the horizontal gradient and decreased along the
      vertical gradient. The heterogeneous sediment properties along gradients
      substantially affected the dominant bacterial groups at the phylum and species
      levels. For example, the NH(+) 4 concentration decreased with increasing depth,
      which was positively correlated with the relative abundance of
      Alphaproteobacteria. The changes in bacterial diversity and dominant bacterial
      groups showed that the top layer had a different bacterial community structure
      than the deeper layers. Principal component analysis revealed that both
      gradients, not each gradient independently, contributed to the shift in the
      bacterial community structure. A multiple linear regression model explained the
      changes in bacterial diversity and richness along the depth and distance
      gradients. Overall, our results suggest that spatial gradients associated with
      sediment properties shaped the bacterial communities in the Poyang Lake beach
      wetland. 

PMID- 25767467
TI  - The broad-spectrum antibiotic, zeamine, kills the nematode worm Caenorhabditis
      elegans.
AB  - Soil bacteria can be prolific producers of secondary metabolites and other
      biologically active compounds of economic and clinical importance. These natural
      products are often synthesized by large multi-enzyme complexes such as polyketide
      synthases (PKSs) or non-ribosomal peptide synthases (NRPSs). The plant-associated
      Gram-negative bacterium, Serratia plymuthica A153, produces several secondary
      metabolites and is capable of killing the nematode worm Caenorhabditis elegans; a
      commonly used model for the study of bacterial virulence. In this study, we show
      that disruption of the hybrid PKS/NRPS zeamine (zmn) gene cluster results in the
      attenuation of "fast-killing" of C. elegans, indicating that zeamine has
      nematicidal activity. C. elegans also exhibits age-dependent susceptibility to
      zeamine, with younger worms being most sensitive to the bioactive molecule. The
      zmn gene cluster is widely distributed within Serratia and phytopathogenic
      Dickeya species and investigation of strains harboring the zmn gene cluster
      showed that several of them are highly virulent in C. elegans. Zeamine was
      described previously as a phytotoxin and broad-spectrum antibacterial compound.
      In addition to its nematicidal properties, we show here that zeamine can also
      kill Saccharomyces cerevisiae and Schizosaccharomyces pombe. The expression of
      the zmn gene cluster and regulation of zeamine production were also investigated.
      Transcription of the cluster was growth phase-dependent, and was modulated by the
      post-transcriptional RNA chaperone, Hfq. The results of this study show that
      zeamine is a highly toxic molecule with little, or no, apparent host specificity
      in very diverse biological systems. In its current form, zeamine(s) may be useful
      as a lead compound suitable for chemical modification and structure-activity
      assays. However, because of widespread non-selective toxicity in multiple
      bioassays, unmodified zeamine(s) is unlikely to be suitable as a therapeutic
      antibiotic. 

PMID- 25767468
TI  - Ecological perspectives on synthetic biology: insights from microbial population
      biology.
AB  - The metabolic capabilities of microbes are the basis for many major
      biotechnological advances, exploiting microbial diversity by selection or
      engineering of single strains. However, there are limits to the advances that can
      be achieved with single strains, and attention has turned toward the metabolic
      potential of consortia and the field of synthetic ecology. The main challenge for
      the synthetic ecology is that consortia are frequently unstable, largely because
      evolution by constituent members affects their interactions, which are the basis
      of collective metabolic functionality. Current practices in modeling consortia
      largely consider interactions as fixed circuits of chemical reactions, which
      greatly increases their tractability. This simplification comes at the cost of
      essential biological realism, stripping out the ecological context in which the
      metabolic actions occur and the potential for evolutionary change. In other
      words, evolutionary stability is not engineered into the system. This realization
      highlights the necessity to better identify the key components that influence the
      stable coexistence of microorganisms. Inclusion of ecological and evolutionary
      principles, in addition to biophysical variables and stoichiometric modeling of
      metabolism, is critical for microbial consortia design. This review aims to bring
      ecological and evolutionary concepts to the discussion on the stability of
      microbial consortia. In particular, we focus on the combined effect of spatial
      structure (connectivity of molecules and cells within the system) and ecological
      interactions (reciprocal and non-reciprocal) on the persistence of microbial
      consortia. We discuss exemplary cases to illustrate these ideas from published
      studies in evolutionary biology and biotechnology. We conclude by making clear
      the relevance of incorporating evolutionary and ecological principles to the
      design of microbial consortia, as a way of achieving evolutionarily stable and
      sustainable systems. 

PMID- 25767469
TI  - CD4+CD25+CD127(low) Regulatory T Cells Play Predominant Anti-Tumor Suppressive
      Role in Hepatitis B Virus-Associated Hepatocellular Carcinoma.
AB  - BACKGROUND: Hepatocellular carcinoma (HCC) is the second leading cause of cancer
      death worldwide and hepatitis B is one of the commonest causes. T regulatory
      cells (Tregs) are strong immunomodulators and are likely to play a major role in
      HCC development. HBV infection is reported to induce expansion of Tregs. We
      investigated the CD4+CD25+CD127(-ve)FoxP3+ Tregs in HBV-related HCC as compared
      to non-HBV-HCC. PATIENTS AND METHODS: Whole blood immunophenotyping was analyzed
      by multicolor flow cytometry in patients with HBV-related HCC (HBV-HCC, n = 17),
      non-HBV-HCC (n = 22; NASH = 16, alcohol-related = 6), and chronic hepatitis B
      infection (CHBV; n = 10). Tregs functionality was checked by in vitro suppression
      assays using CD4+ CD25+ CD127(low) Tregs. Levels of serum alpha-fetoprotein
      (AFP), expression of FoxP3, IL-10, PD1, TGF-beta, and Notch in Tregs, and liver
      explants were analyzed by flow cytometry, immunohistochemistry, and quantitative
      RT-PCR. RESULTS: CD4+CD25+(hi) and Foxp3 expression in CD4+CD25+(hi)CD127(low)
      was significantly increased (P = 0.04, P = 0.007) in HBVHCC compared to non
      HBVHCC and CHBV patients. HBVHCC also showed high IL-10 and TGF-beta secreting
      CD4 + CD25 + (hi)Tregs. The PD1 expression in CD4 + CD25+(hi) was significantly
      decreased in the HBVHCC than non-HBVHCC. In HBVHCC, AFP levels were significantly
      high (median 941, range 2-727940) than non-HBVHCC (median 13.5, range 2-18,900).
      In HBVHCC, patients with high AFP (range; 3982-727940 ng/ml) showed positive
      correlation with Foxp3 expression in CD4+CD25+(hi) CD127(low) (r = 0.857, P =
      0.014). Reduced PD1 expression in HBVHCC also had negative correlation with FOXP3
      in CD4+CD25+(hi) CD127(low) (r = -0.78, P = 0.04). However, AFP levels in non
      HBVHCC showed negative correlation with (R = -0.67, P = 0.005) with CD4+CD25+(hi)
      Tregs. CONCLUSION: Our results demonstrate that CD4+ CD25+(hi) Tregs from HBVHCC
      patients have decreased expression of PD1, resulting in higher IL-10 and TGF-beta
      secretion. Increased suppressive ability of Tregs in HBV-related HCC confers
      increased anti-tumor suppressive response than in non-HBV-HCC. Modulation of
      Tregs and PD1 may serve as useful therapeutic targets.

PMID- 25767470
TI  - Methodologies for the Analysis of HCV-Specific CD4(+) T Cells.
AB  - Virus-specific CD4(+) T cells play a major role in viral infections, such as
      hepatitis C virus (HCV). Viral clearance is associated with vigorous and multi
      specific CD4(+) T-cell responses, while chronic infection has been shown to be
      associated with weak or absent T-cell responses. Most of these studies have used
      functional assays to analyze virus-specific CD4(+) T-cell responses; however,
      these and other detection methods have various limitations. Therefore, the
      important question of whether virus-specific CD4(+) T cells are completely absent
      or primarily impaired in specific effector functions during chronic infection,
      has yet to be analyzed in detail. A novel assay, in which virus-specific CD4(+) T
      cell frequencies can be determined by de novo CD154 (CD40 ligand) expression in
      response to viral antigens, can help to overcome some of the limitations of
      functional assays and restrictions of multimer-based methods. This and other
      current established methods for the detection of HCV-specific CD4(+) T cells will
      be discussed in this review. 

PMID- 25767471
TI  - Thymic stromal alterations and genetic disorders of immune system.

PMID- 25767473
TI  - Predawn and high intensity application of supplemental blue light decreases the
      quantum yield of PSII and enhances the amount of phenolic acids, flavonoids, and
      pigments in Lactuca sativa.
AB  - To evaluate the effect of blue light intensity and timing, two cultivars of
      lettuce [Lactuca sativa cv. "Batavia" (green) and cv. "Lollo Rossa" (red)] were
      grown in a greenhouse compartment in late winter under natural light and
      supplemental high pressure sodium (SON-T) lamps yielding 90 (+/-10) MUmol m(-2)
      s(-1) for up to 20 h, but never between 17:00 and 21:00. The temperature in the
      greenhouse compartments was 22/11 degrees C day/night, respectively. The five
      light-emitting diode (LED) light treatments were Control (no blue addition), 1B
      06-08 (Blue light at 45 MUmol m(-2) s(-1) from 06:00 to 08:00), 1B 21-08 (Blue
      light at 45 MUmol m(-2) s(-1) from 21:00 to 08:00), 2B 17-19 (Blue at 80 MUmol m(
      2) s(-1) from 17:00 to 19:00), and 1B 17-19 (Blue at 45 MUmol m(-2) s(-1) from
      17:00 to 19:00). Total fresh and dry weight was not affected with additional blue
      light; however, plants treated with additional blue light were more compact. The
      stomatal conductance in the green lettuce cultivar was higher for all treatments
      with blue light compared to the Control. Photosynthetic yields measured with
      chlorophyll fluorescence showed different response between the cultivars; in red
      lettuce, the quantum yield of PSII decreased and the yield of non-photochemical
      quenching increased with increasing blue light, whereas in green lettuce no
      difference was observed. Quantification of secondary metabolites showed that all
      four treatments with additional blue light had higher amount of pigments,
      phenolic acids, and flavonoids compared to the Control. The effect was more
      prominent in red lettuce, highlighting that the results vary among treatments and
      compounds. Our results indicate that not only high light level triggers
      photoprotective heat dissipation in the plant, but also the specific spectral
      composition of the light itself at low intensities. However, these plant
      responses to light are cultivar dependent. 

PMID- 25767474
TI  - A high-sensitivity optical device for the early monitoring of plant pathogen
      attack via the in vivo detection of ROS bursts.
AB  - Biotic stressors, especially pathogenic microorganisms, are rather difficult to
      detect. In plants, one of the earliest cellular responses following pathogen
      infection is the production of reactive oxygen species (ROS). In this study, a
      novel optical device for the early monitoring of Pseudomonas attack was
      developed; this device measures the ROS level via oxidation-sensitive 2', 7'
      dichlorodihydrofluorescein diacetate (H2DCFDA)-mediated fluorescence, which could
      provide early monitoring of attacks by a range of plant pathogen; ROS bursts were
      detected in vivo in Arabidopsis thaliana with higher sensitivity and accuracy
      than those of a commercial luminescence spectrophotometer. Additionally, the DCF
      fluorescence truly reflected early changes in the ROS level, as indicated by an
      evaluation of the H2O2 content and the tight association between the ROS and
      Pseudomonas concentration. Moreover, compared with traditional methods for
      detecting plant pathogen attacks based on physiological and biochemical
      measurements, our proposed technique also offers significant advantages, such as
      low cost, simplicity, convenient operation and quick turnaround. These results
      therefore suggest that the proposed optical device could be useful for the rapid
      monitoring of attacks by plant pathogen and yield results considerably earlier
      than the appearance of visual changes in plant morphology or growth. 

PMID- 25767472
TI  - Platelets and infections - complex interactions with bacteria.
AB  - Platelets can be considered sentinels of vascular system due to their high number
      in the circulation and to the range of functional immunoreceptors they express.
      Platelets express a wide range of potential bacterial receptors, including
      complement receptors, FcgammaRII, Toll-like receptors but also integrins
      conventionally described in the hemostatic response, such as GPIIb-IIIa or GPIb.
      Bacteria bind these receptors either directly, or indirectly via fibrinogen,
      fibronectin, the first complement C1q, the von Willebrand Factor, etc. The fate
      of platelet-bound bacteria is questioned. Several studies reported the ability of
      activated platelets to internalize bacteria such as Staphylococcus aureus or
      Porphyromonas gingivalis, though there is no clue on what happens thereafter. Are
      they sheltered from the immune system in the cytoplasm of platelets or are they
      lysed? Indeed, while the presence of phagolysosome has not been demonstrated in
      platelets, they contain antimicrobial peptides that were shown to be efficient on
      S. aureus. Besides, the fact that bacteria can bind to platelets via receptors
      involved in hemostasis suggests that they may induce aggregation; this has indeed
      been described for Streptococcus sanguinis, S. epidermidis, or C. pneumoniae. On
      the other hand, platelets are able to display an inflammatory response to an
      infectious triggering. We, and others, have shown that platelet release soluble
      immunomodulatory factors upon stimulation by bacterial components. Moreover,
      interactions between bacteria and platelets are not limited to only these two
      partners. Indeed, platelets are also essential for the formation of neutrophil
      extracellular traps by neutrophils, resulting in bacterial clearance by trapping
      bacteria and concentrating antibacterial factors but in enhancing thrombosis. In
      conclusion, the platelet-bacteria interplay is a complex game; its fine analysis
      is complicated by the fact that the inflammatory component adds to the
      aggregation response. 

PMID- 25767475
TI  - Control of Rubisco function via homeostatic equilibration of CO2 supply.
AB  - Rubisco is the most abundant protein on Earth that serves as the primary engine
      of carbon assimilation. It is characterized by a slow rate and low specificity
      for CO2 leading to photorespiration. We analyze here the challenges of operation
      of this enzyme as the main carbon fixation engine. The high concentration of
      Rubisco exceeds that of its substrate CO2 by 2-3 orders of magnitude; however,
      the total pool of available carbon in chloroplast, i.e., mainly bicarbonate, is
      comparable to the concentration of Rubisco active sites. This makes the reactant
      stationary assumption (RSA), which is essential as a condition of satisfying the
      Michaelis-Menten (MM) kinetics, valid if we assume that the delivery of CO2 from
      this pool is not limiting. The RSA is supported by active carbonic anhydrases
      (CA) that quickly equilibrate bicarbonate and CO2 pools and supply CO2 to
      Rubisco. While the operation of stromal CA is independent of light reactions, the
      thylakoidal CA associated with PSII and pumping CO2 from the thylakoid lumen is
      coordinated with the rate of electron transport, water splitting and proton
      gradient across the thylakoid membrane. At high CO2 concentrations, CA becomes
      less efficient (the equilibrium becomes unfavorable), so a deviation from the MM
      kinetics is observed, consistent with Rubisco reaching its Vmax at approximately
      50% lower level than expected from the classical MM curve. Previously, this
      deviation was controversially explained by the limitation of RuBP regeneration.
      At low ambient CO2 and correspondingly limited capacity of the bicarbonate pool,
      its depletion at Rubisco sites is relieved in that the enzyme utilizes O2 instead
      of CO2, i.e., by photorespiration. In this process, CO2 is supplied back to
      Rubisco, and the chloroplastic redox state and energy level are maintained. It is
      concluded that the optimal performance of photosynthesis is achieved via the
      provision of continuous CO2 supply to Rubisco by carbonic anhydrases and
      photorespiration. 

PMID- 25767476
TI  - Jasmonate-responsive expression of paclitaxel biosynthesis genes in Taxus
      cuspidata cultured cells is negatively regulated by the bHLH transcription
      factors TcJAMYC1, TcJAMYC2, and TcJAMYC4.
AB  - Taxus cell suspension culture is a sustainable technology for the industrial
      production of paclitaxel (Taxol(r)), a highly modified diterpene anti-cancer
      agent. The methyl jasmonate (MJ)-mediated paclitaxel biosynthetic pathway is not
      fully characterized, making metabolic engineering efforts difficult. Here,
      promoters of seven genes (TASY, T5alphaH, DBAT, DBBT, PAM, BAPT, and DBTNBT),
      encoding enzymes of the paclitaxel biosynthetic pathway were isolated and used to
      drive MJ-inducible expression of a GUS reporter construct in transiently
      transformed Taxus cells, showing that elicitation of paclitaxel production by MJ
      is regulated at least in part at the level of transcription. The paclitaxel
      biosynthetic pathway promoters contained a large number of E-box sites (CANNTG),
      similar to the binding sites for the key MJ-inducible transcription factor AtMYC2
      from Arabidopsis thaliana. Three MJ-inducible MYC transcription factors similar
      to AtMYC2 (TcJAMYC1, TcJAMYC2, and TcJAMYC4) were identified in Taxus.
      Transcriptional regulation of paclitaxel biosynthetic pathway promoters by
      transient over expression of TcJAMYC transcription factors indicated a negative
      rather than positive regulatory role of TcJAMYCs on paclitaxel biosynthetic gene
      expression. 

PMID- 25767477
TI  - Utilization of farm animal genetic resources in a changing agro-ecological
      environment in the Nordic countries.
AB  - Livestock production is the most important component of northern European
      agriculture and contributes to and will be affected by climate change.
      Nevertheless, the role of farm animal genetic resources in the adaptation to new
      agro-ecological conditions and mitigation of animal production's effects on
      climate change has been inadequately discussed despite there being several
      important associations between animal genetic resources and climate change
      issues. The sustainability of animal production systems and future food security
      require access to a wide diversity of animal genetic resources. There are several
      genetic questions that should be considered in strategies promoting adaptation to
      climate change and mitigation of environmental effects of livestock production.
      For example, it may become important to choose among breeds and even among farm
      animal species according to their suitability to a future with altered production
      systems. Some animals with useful phenotypes and genotypes may be more useful
      than others in the changing environment. Robust animal breeds with the potential
      to adapt to new agro-ecological conditions and tolerate new diseases will be
      needed. The key issue in mitigation of harmful greenhouse gas effects induced by
      livestock production is the reduction of methane (CH4) emissions from ruminants.
      There are differences in CH4 emissions among breeds and among individual animals
      within breeds that suggest a potential for improvement in the trait through
      genetic selection. Characterization of breeds and individuals with modern genomic
      tools should be applied to identify breeds that have genetically adapted to
      marginal conditions and to get critical information for breeding and conservation
      programs for farm animal genetic resources. We conclude that phenotyping and
      genomic technologies and adoption of new breeding approaches, such as genomic
      selection introgression, will promote breeding for useful characters in livestock
      species. 

PMID- 25767479
TI  - History, chance and selection during phenotypic and genomic experimental
      evolution: replaying the tape of life at different levels.

PMID- 25767478
TI  - Substrate recognition and function of the R2TP complex in response to cellular
      stress.
AB  - The R2TP complex is a HSP90 co-chaperone, which consists of four subunits:
      PIH1D1, RPAP3, RUVBL1, and RUVBL2. It is involved in the assembly of large
      protein or protein-RNA complexes such as RNA polymerase, small nucleolar
      ribonucleoproteins (snoRNPs), phosphatidylinositol 3 kinase-related kinases
      (PIKKs), and their complexes. While RPAP3 has a HSP90 binding domain and the
      RUVBLs comprise ATPase activities important for R2TP functions, PIH1D1 contains a
      PIH-N domain that specifically recognizes phosphorylated substrates of the R2TP
      complex. In this review we provide an overview of the current knowledge of the
      R2TP complex with the focus on the recently identified structural and mechanistic
      features of the R2TP complex functions. We also discuss the way R2TP regulates
      cellular response to stress caused by low levels of nutrients or by DNA damage
      and its possible exploitation as a target for anti-cancer therapy. 

PMID- 25767481
TI  - Proteolipid protein 1 gene sequencing of hereditary spastic paraplegia.
AB  - PCR amplification and sequencing of whole blood DNA from an individual with
      hereditary spastic paraplegia, as well as family members, revealed a fragment of
      proteolipid protein 1 (PLP1) gene exon 1, which excluded the possibility of
      isomer 1 expression for this family. The fragment sequence of exon 3 and exon 5
      was consistent with the proteolipid protein 1 sequence at NCBI. In the proband
      samples, a PLP1 point mutation in exon 4 was detected at the basic group of
      position 844, T->C, phenylalanine->leucine. In proband samples from a male
      cousin, the basic group at position 844 was C, but gene sequencing signals
      revealed mixed signals of T and C, indicating possible mutation at this locus.
      Results demonstrated that changes in PLP1 exon 4 amino acids were associated with
      onset of hereditary spastic paraplegia. 

PMID- 25767480
TI  - Influence of RNA interference on the mitochondrial subcellular localization of
      alpha-synuclein and on the formation of Lewy body-like inclusions in the
      cytoplasm of human embryonic kidney 293 cells induced by the overexpression of
      alpha-synuclein.
AB  - The specific and effective alpha-synuclein RNA interference (RNAi) plasmids, and
      the alpha-synuclein-pEGFP recombinant plasmids were co-transfected into human
      embryonic kidney 293 (HEK293) cells using the lipofectamine method. Using an
      inverted fluorescence microscope, alpha-synuclein proteins were observed to
      aggregate in the cytoplasm and nucleus. Wild-type alpha-synuclein proteins co
      localized with mitochondria. Hematoxylin-eosin staining revealed round
      eosinophilic bodies (Lewy body-like inclusions) in the cytoplasm of some cells
      transfected with alpha-synuclein-pEGFP plasmid. However, the formation of Lewy
      body-like inclusions was not observed following transfection with the RNAi pSYN-1
      plasmid. RNAi blocked Lewy body-like inclusions in the cytoplasm of HEK293 cells
      induced by wild-type alpha-synuclein overexpression, but RNAi did not affect the
      subcellular localization of wild-type alpha-synuclein in mitochondria. 

PMID- 25767482
TI  - Correlation between human seizure-related gene 6 variants and idiopathic
      generalized epilepsy in a Southern Chinese Han population.
AB  - This study sought to analyze the genotype and gene mutations of human seizure
      related gene 6 in 98 patients with idiopathic generalized epilepsy (non-febrile
      seizures), who were selected from three generations of the Chinese Han population
      living in Shanghai, Zhejiang Province, Wuxi of Jiangsu Province, and Jiangxi
      Province of Southern China. Twenty-six patients' parents were available as a
      first-degree relatives group and 100 biologically unrelated healthy controls were
      collected as the control group. Based on the age of onset and seizure type, the
      patients were divided into six subgroups. Polymerase chain reaction and DNA
      direct sequencing analysis showed that the most frequent mutations c.1249dupC
      (p.Gly418Argfx31) and c.1636A > G (p.Thr546Ala) were detected in some idiopathic
      generalized epilepsy patients and their asymptomatic first-degree relatives
      (30.6% vs. 19.2% and 11.2% vs. 26.9%). A novel mutation c.1807G > A (p.Val603Met)
      was found in a patient with late-onset idiopathic generalized epilepsy. There was
      no significant difference in the incidence of these three mutations among the
      different subgroups of idiopathic generalized epilepsy and controls. Thus,
      further analysis of a larger population is needed to confirm the assumption that
      human seizure-related gene 6 is a susceptibility gene for idiopathic generalized
      epilepsy with various sub-syndromes. 

PMID- 25767483
TI  - Changes in social emotion recognition following traumatic frontal lobe injury.
AB  - Changes in social and emotional behaviour have been consistently observed in
      patients with traumatic brain injury. These changes are associated with emotion
      recognition deficits which represent one of the major barriers to a successful
      familiar and social reintegration. In the present study, 32 patients with
      traumatic brain injury, involving the frontal lobe, and 41 age- and education
      matched healthy controls were analyzed. A Go/No-Go task was designed, where each
      participant had to recognize faces representing three social emotions (arrogance,
      guilt and jealousy). Results suggested that ability to recognize two social
      emotions (arrogance and jealousy) was significantly reduced in patients with
      traumatic brain injury, indicating frontal lesion can reduce emotion recognition
      ability. In addition, the analysis of the results for hemispheric lesion location
      (right, left or bilateral) suggested the bilateral lesion sub-group showed a
      lower accuracy on all social emotions. 

PMID- 25767484
TI  - The calcium uniporter regulates the permeability transition pore in isolated
      cortical mitochondria.
AB  - To investigate the influence of the mitochondrial calcium uniporter on the
      mitochondrial permeability transition pore, the present study observed
      mitochondrial morphology in cortical neurons isolated from adult rats using
      transmission electron microscopy, and confirmed the morphology and activity of
      isolated mitochondria by detecting succinic dehydrogenase and monoamine oxidase,
      two mitochondrial enzymes. Isolated mitochondria were treated with either
      ruthenium red, an inhibitor of the uniporter, spermine, an activator of the
      uniporter, or in combination with cyclosporin A, an inhibitor of the
      mitochondrial permeability transition pore. Results showed that ruthenium red
      inhibited CaCl2-induced mitochondrial permeability transition pore opening,
      spermine enhanced opening, and cyclosporin A attenuated the effects of spermine.
      Results demonstrated that the mitochondrial calcium uniporter plays a role in
      regulating the mitochondrial permeability transition pore in mitochondria
      isolated from the rat brain cortex. 

PMID- 25767485
TI  - Effects of minocycline on learning and memory of mice following ischemic-hypoxic
      cerebral injuries.
AB  - An ischemic-hypoxic animal model was established using right common carotid
      artery occlusions and inhalation of low concentrations of oxygen in mice. At 10
      days after the ischemic-hypoxic injuries, saline-treated mice exhibited
      significantly prolonged escape latencies in water-maze tests and significantly
      shorter memory latencies and more mistakes in step-down tests. In contrast, mice
      treated with 5 mg/kg minocycline exhibited significant reversals of each of these
      effects compared with the saline-treated control mice. Moreover, we found that
      minocycline can relieve brain water content and morphological changes in mice
      following ischemic-hypoxic cerebral injuries. Accordingly, our findings indicate
      that minocycline provides some protections against the deleterious effects of
      these injuries in mice. 

PMID- 25767486
TI  - Altered expression of metabotropic glutamate receptor 1 alpha after acute diffuse
      brain injury: Effect of the competitive antagonist 1-aminoindan-1, 5-dicarboxylic
      acid.
AB  - The diffuse brain injury model was conducted in Sprague-Dawley rats, according to
      Marmarou's free-fall attack. The water content in brain tissue, expression of
      metabotropic glutamate receptor 1alpha mRNA and protein were significantly
      increased after injury, reached a peak at 24 hours, and then gradually decreased.
      After treatment with the competitive antagonist of metabotropic glutamate
      receptor 1alpha, (RS)-1-aminoindan-1, 5-dicarboxylic acid, the water content of
      brain tissues decreased between 12-72 hours after injury, and neurological
      behaviors improved at 2 weeks. These experimental findings suggest that the 1
      aminoindan-1, 5-dicarboxylic acid may result in marked neuroprotection against
      diffuse brain injury. 

PMID- 25767487
TI  - Dynamic expression of cerebral cortex and hippocampal glutamate transporters in a
      rat model of chest compression-induced global cerebral ischemia.
AB  - The present study established a rat model of global cerebral ischemia induced by
      chest compression for six minutes to dynamically observe expressional changes of
      three glutamate transporters in the cerebral cortex and hippocampus. After 24
      hours of ischemia, expression of glutamate transporter-1 significantly decreased
      in the cerebral cortex and hippocampus, which was accompanied by neuronal
      necrosis. At 7 days post-ischemia, expression of excitatory amino acid carrier 1
      decreased in the hippocampal CA1 region and cortex, and was accompanied by
      apoptosis. Expression of glutamate-aspartate transporter remained unchanged at 6
      hours-7 days after ischemia. These results suggested that glutamate transporter
      levels were altered at different periods of cerebral ischemia. 

PMID- 25767488
TI  - Rizatriptan benzoate influences the endogenous pain modulatory system in a rat
      model of migraine.
AB  - The present study utilized a nitroglycerin-induced rat model of migraine to
      detect the effects of rizatriptan benzoate on proenkephalin and substance P gene
      expression in the midbrain using real-time quantitative polymerase chain reaction
      and investigate whether rizatriptan benzoate can regulate the endogenous pain
      modulatory system. The results showed that rizatriptan benzoate significantly
      reduced expression of the mRNAs for proenkephalin and substance P. Rizatriptan
      benzoate may inhibit the analgesic effect of the endogenous pain modulatory
      system. 

PMID- 25767489
TI  - Calcium channel blockers and Alzheimer's disease.
AB  - Alzheimer's disease is characterized by two pathological hallmarks: amyloid
      plaques and neurofibrillary tangles. In addition, calcium homeostasis is
      disrupted in the course of human aging. Recent research shows that dense plaques
      can cause functional alteration of calcium signals in mice with Alzheimer's
      disease. Calcium channel blockers are effective therapeutics for treating
      Alzheimer's disease. This review provides an overview of the current research of
      calcium channel blockers involved in Alzheimer's disease therapy. 

PMID- 25767490
TI  - The role of autophagy in Parkinson's disease.
AB  - Although Parkinson's disease is the most common neurodegenerative movement
      disorder, the mechanisms of pathogenesis remain poorly understood. Recent
      findings have shown that deregulation of the autophagy-lysosome pathway is
      involved in the pathogenesis of Parkinson's disease. This review summarizes the
      most recent findings and discusses the unique role of the autophagy-lysosome
      pathway in Parkinson's disease to highlight the possibility of Parkinson's
      disease treatment strategies that incorporate autophagy-lysosome pathway
      modulation. 

PMID- 25767491
TI  - Tissue plasminogen activator-independent roles of neuroserpin in the central
      nervous system.
AB  - A number of studies have confirmed the existence of tissue-type plasminogen
      activator-independent roles of neuroserpin, a member of the serine protease
      inhibitor superfamily. In this review article, we aim to clarify this role. These
      unique roles of neuroserpin are involved in its neuroprotective effect during
      ischemic brain injury, its regulation of tumorigenesis, and the mediation of
      emotion and cognition through the inhibition of urokinase-type plasminogen
      activator and fibrinolysin, modification of Th cells, reducing plaque formation,
      promoting process growth and intracellular adhesion, and altering the expression
      of cadherin and nuclear factor kappa B. 

PMID- 25767492
TI  - Literature study on clinical treatment of facial paralysis in the last 20 years
      using Web of Science: Comparison between rehabilitation, physiotherapy and
      acupuncture.
AB  - BACKGROUND: Facial paralysis is defined as severe or complete loss of facial
      muscle motor function. OBJECTIVE: The study was undertaken to explore a
      bibliometric approach to quantitatively assess the research on clinical treatment
      of facial paralysis using rehabilitation, physiotherapy and acupuncture using Web
      of Science from 1992 to 2011. DESIGN: Bibliometric approach. DATA RETRIEVAL: A
      bibliometric analysis based on the publications on Web of Science was performed
      using key words such as "facial paralysis", "rehabilitation", "physiotherapy" and
      "acupuncture". INCLUSIVE CRITERIA: (1) Research articles on the clinical
      treatment of facial paralysis using acupuncture or physiotherapy (e.g. exercise,
      electro-stimulation) and other rehabilitation methods; (2) researches on human
      and animal fundamentals, clinical trials and case reports; (3) Article types:
      article, review, proceedings paper, note, letter, editorial material, discussion,
      book chapter. (4) Publication year: 1992-2011 inclusive. EXCLUSION CRITERIA: (1)
      Articles on the causes and diagnosis on facial paralysis; (2) Type of articles:
      correction; (3) Articles from following databases: all databases related to
      social science and chemical databases in Web of Science. MAIN OUTCOME MEASURES:
      (1) Overall number of publications; (2) number of publications annually; (3)
      number of citations received annually; (4) top cited paper; (5) subject
      categories of publication; (6) the number of countries in which the article is
      published; (7) distribution of output in journals. RESULTS: Overall population
      stands at 3 543 research articles addressing the clinical treatment of facial
      paralysis in Web of Science during the study period. There is also a markedly
      increase in the number of publications on the subject "facial paralysis
      treatments using rehabilitation" during the first decade of the 21(st) century,
      except in 2004 and 2006 when there are perceptible drops in the number of
      articles published. The only other year during the study period saw such a drop
      is 1993. Specifically, there are 192 published articles on facial paralysis
      treated by rehabilitation in the past two decades, far more than the output of
      physiotherapy treatment. Physiotherapy treatment scored only 25 articles
      including acupuncture treatment, with over 80% of these written by Chinese
      researchers and clinicians. Ranked by regions, USA is by far the most productive
      country in terms of the number of publications on facial paralysis rehabilitation
      and physiotherapy research. Seeing from another angle, the journals that focus on
      otolaryngology published the most number of articles in rehabilitation and
      physiotherapy studies, whereas most acupuncture studies on facial paralysis were
      published in the alternative and complementary medicine journals. CONCLUSION:
      Study of facial paralysis remains an area of active investigation and innovation.
      Further clinical studies in humans addressing the use of growth factors or stem
      cells continue to successful facial nerve regeneration.

PMID- 25767493
TI  - Anchanling reduces pathology in a lactacystin- induced Parkinson's disease model.
AB  - A rat model of Parkinson's disease was induced by injecting lactacystin
      stereotaxically into the left mesencephalic ventral tegmental area and substantia
      nigra pars compacta. After rats were intragastrically perfused with Anchanling, a
      Chinese medicine, mainly composed of magnolol, for 5 weeks, when compared with
      Parkinson's disease model rats, tyrosine hydroxylase expression was increased,
      alpha-synuclein and ubiquitin expression was decreased, substantia nigra cell
      apoptosis was reduced, and apomorphine-induced rotational behavior was improved.
      Results suggested that Anchanling can ameliorate Parkinson's disease pathology
      possibly by enhancing degradation activity of the ubiquitin-proteasome system. 

PMID- 25767494
TI  - Protective effects of curcumin against human immunodeficiency virus 1 gp120 V3
      loop-induced neuronal injury in rats.
AB  - Curcumin improves the learning and memory deficits in rats induced by the gp120
      V3 loop. The present study cultured rat hippocampal neurons with 1 nM gp120 V3
      loop and 1 MUM curcumin for 24 hours. The results showed that curcumin inhibited
      the gp120 V3 loop-induced mitochondrial membrane potential decrease, reduced the
      mRNA expression of the pro-apoptotic gene caspase-3, and attenuated hippocampal
      neuronal injury. 

PMID- 25767496
TI  - Effect of single-use versus combined-use moschus and diazepam on expression of
      amino acid neurotransmitters in the rat corpus striatum.
AB  - The present study analyzed expressional changes of excitatory neurotransmitters
      and inhibitory neurotransmitters in the rat corpus striatum after single-use and
      combined-use diazepam and Chinese herb moschus. The influence of moschus on the
      central nervous system was analyzed, in particular whether moschus increased
      penetration of other drugs into the brain. Reverse-phase high-performance liquid
      chromatography, which included pre-column derivation with orthophthaladehyde
      detection, showed varied increased levels of excitatory neurotransmitters,
      including aspartate and glutamate, and inhibitory neurotransmitters, including
      glycine and gamma-aminobutyric acid, in the corpus striatum after treatment with
      moschus alone, diazepam alone, or a combination of both. Compared with the
      diazepam group, aspartate levels significantly decreased at 30 and 60-105 minutes
      after combined treatment with moschus, while glutamate significantly increased at
      45 and 75-105 minutes, glycine levels significantly increased at 105 minutes, and
      gamma-aminobutyric acid increased at 30 and 75-105 minutes. These findings
      suggested that moschus increased the inhibition effects of diazepam on the brain.

PMID- 25767495
TI  - Neuroprotective effects of total saponins from Rubus parvifolius L. on cerebral
      ischemia/reperfusion injury in rats.
AB  - This study examines the neuroprotective effects and mechanisms of action of total
      saponins from Rubus parvifolius L. (TSRP) on focal cerebral ischemia and
      reperfusion injury in rats. Focal cerebral ischemia and reperfusion injury was
      performed in rats using the suture method. The results indicate that intragastric
      injection of TSRP, at 5, 10 and 20 mg/kg, could decrease neurological impairment,
      reduce cerebral infarct volume, diminish pathological changes, and significantly
      inhibit the apoptosis of neurons surrounding the ischemic area. In addition, TSRP
      upregulated the expression of the anti-apoptotic factor Bcl-2, at the protein and
      mRNA levels, and it downregulated the expression of the pro-apoptotic factor Bax,
      at the protein and mRNA levels. These findings indicate that TSRP protects
      against cerebral ischemia/reperfusion injury, and that it may do so by regulating
      the expression of Bcl-2 and Bax. 

PMID- 25767497
TI  - Influence of Xingnao Jieyu capsule on hippocampal and frontal lobe neuronal
      growth in a rat model of post-stroke depression.
AB  - The present study established a rat model of post-stroke depression using
      incomplete ischemia induced by unilateral carotid artery ligation in combination
      with solitary raising and subcutaneous injection of a small dose of reserpine.
      After intragastric perfusion with 45 mg/100 g, 15 mg/100 g, and 7.5 mg/100 g of
      Xingnao Jieyu for 7, 14 and 21 days, neuronal morphology in the frontal lobe and
      hippocampus was improved, depression state and voluntary behaviors were also
      effectively improved in rats with post-stroke depression. Moreover, the effects
      of Xingnao Jieyu at a dose of 45 and 15 mg/100 g were similar to the traditional
      antidepressant Prozac. 

PMID- 25767498
TI  - Effects of Yulangsan polysaccharide on monoamine neurotransmitters, adenylate
      cyclase activity and brain-derived neurotrophic factor expression in a mouse
      model of depression induced by unpredictable chronic mild stress.
AB  - The present study established a mouse model of depression induced by
      unpredictable chronic mild stress. The model mice were treated with Yulangsan
      polysaccharide (YLSPS; 150, 300 and 600 mg/kg) for 21 days, and compared with
      fluoxetine-treated and normal control groups. Enzyme-linked immunosorbent assay,
      radioimmunity and immunohistochemical staining showed that following treatment
      with YLSPS (300 and 600 mg/kg), monoamine neurotransmitter levels, prefrontal
      cortex adenylate cyclase activity and hippocampal brain-derived neurotrophic
      factor expression were significantly elevated, and depression-like behaviors were
      improved. Open-field and novelty-suppressed feeding tests showed that mouse
      activity levels were increased and feeding latency was shortened following
      treatment. Our results indicate that YLSPS inhibits depression by upregulating
      monoamine neurotransmitters, prefrontal cortex adenylate cyclase activity and
      hippocampal brain-derived neurotrophic factor expression. 

PMID- 25767499
TI  - Sericin can reduce hippocampal neuronal apoptosis by activating the Akt signal
      transduction pathway in a rat model of diabetes mellitus.
AB  - In the present study, a rat model of type 2 diabetes mellitus was established by
      continuous peritoneal injection of streptozotocin. Following intragastric
      perfusion of sericin for 35 days, blood glucose levels significantly reduced,
      neuronal apoptosis in the hippocampal CA1 region decreased, hippocampal
      phosphorylated Akt and nuclear factor kappa B expression were enhanced, but Bcl
      xL/Bcl-2 associated death promoter expression decreased. Results demonstrated
      that sericin can reduce hippocampal neuronal apoptosis in a rat model of diabetes
      mellitus by regulating abnormal changes in the Akt signal transduction pathway. 

PMID- 25767500
TI  - Protective effects of Purendan superfine powder on retinal neuron apoptosis in a
      rat model of type 2 diabetes mellitus.
AB  - This study sought to investigate the effects of Purendan superfine powder
      comprised of Momordica charantia, Radix Ginseng, and Radix Salviae Miltiorrhiae
      on neuronal apoptosis and expression of bcl-2, bax, and caspase-3, which are
      retinal apoptosis-associated factors in rats with diabetes mellitus induced by
      continuous intraperitoneal injection of streptozotocin. The results showed that
      Purendan superfine powder could upregulate the expression of bcl-2 protein and
      mRNA, and downregulate the expression of bax and caspase-3 in the retina of
      diabetes mellitus rats. In addition, Purendan superfine powder was shown to
      reduce the number of apoptotic neurons. Our experimental findings indicate that
      Purendan superfine powder can inhibit neuronal apoptosis in the retina of
      diabetes mellitus rats and has protective effects on diabetic retinopathy. 

PMID- 25767501
TI  - Effects of electroacupuncture on the expression of p70 ribosomal protein S6
      kinase and ribosomal protein S6 in the hippocampus of rats with vascular
      dementia.
AB  - This study investigated the mechanism underlying electroacupuncture therapy for
      vascular dementia through electroacupuncture at the acupoints of Baihui (DU20),
      Dazhui (DU14), and bilateral Shenshu (BL23) in a rat model of vascular dementia
      produced by bilateral middle cerebral artery occlusion. Morris water maze test
      showed that electroacupuncture improved the learning ability of vascular dementia
      rats. Western blot assay revealed that the expression of p70 ribosomal protein S6
      kinase and ribosomal protein S6 in vascular dementia rats was significantly
      increased after electroacupuncture, compared with the model group that was not
      treated with acupuncture. The average escape latency was also shortened after
      electroacupuncture, and escape strategies in the spatial probe test improved from
      edge and random searches, to linear and trending swim pathways. The experimental
      findings indicate that electroacupuncture improves learning and memory ability by
      up-regulating expression of p70 ribosomal protein S6 kinase and ribosomal protein
      S6 in the hippocampus of vascular dementia rats. 

PMID- 25767502
TI  - Acupuncture effects on the hippocampal cholinergic system in a rat model of
      neuropathic pain.
AB  - The present study observed the effects of repeated electroacupuncture of Zusanli
      (ST36) and Yanglingquan (GB34) on expression of hippocampal acetylcholinesterase,
      vesicular acetylcholine transporter, and muscarinic M1 receptor mRNA in chronic
      constrictive injury (neuropathic pain) and/or ovariotomy rats. Results
      demonstrated increased expression of hippocampal acetylcholinesterase, vesicular
      acetylcholine transporter, and muscarinic M1 receptor mRNA, as well as decreased
      pain threshold, in a rat model of chronic neuropathic pain after
      electroacupuncture. The effects of electroacupuncture increased with prolonged
      time, but the above-mentioned effects decreased in memory-deficient animals.
      Results indicated that repeated electroacupuncture has a cumulative analgesic
      effect, which is closely associated with upregulation of acetylcholinesterase and
      vesicular acetylcholine transporter activity, as well as M1 receptor mRNA
      expression and memory. 

PMID- 25767503
TI  - Analgesic action of suspended moxibustion in rats with chronic visceral
      hyperalgesia correlates with enkephalins in the spinal cord.
AB  - Rats that modeled chronic visceral hyperalgesia received suspended moxibustion at
      bilateral Tianshu (ST25) and Shangjuxu (ST37) once daily over a period of 7 days.
      Results show that suspended moxibustion significantly depressed abdominal
      withdrawal reflex scores and increased enkephalin concentration in the spinal
      cord. The experimental findings suggest that spinal enkephalins contributed to
      the analgesic effect of suspended moxibustion in rats with chronic visceral
      hyperalgesia. 

PMID- 25767504
TI  - Cerebral autosomal dominant arteriopathy with subcortical infarcts and
      leukoencephalopathy in a Chinese pedigree: A case report using brain magnetic
      resonance imaging and biospy.
AB  - The present study enrolled a Chinese family that comprised 34 members and spanned
      three generations. Eight members were diagnosed with cerebral autosomal dominant
      arteriopathy with subcortical infarcts and leukoencephalopathy, and disease
      diagnoses corresponded with autosomal incomplete dominance inheritance. The
      primary clinical manifestations included paralysis, dysarthria, and mild
      cognitive deficits. Magnetic resonance imaging revealed diffuse
      leukoencephalopathy with involvement of bilateral anterior temporal lobes, in
      particular the pons. In addition, multiple cerebral infarction was identified in
      the proband. Sural nerve biopsy findings of the proband revealed granular
      osmophilic material deposits in the extracellular matrix, which were adjacent to
      smooth muscle cells of dermal arterioles. Screening exons 2-4 for NOTCH 3
      mutations by direct sequencing did not reveal any abnormalities. 

PMID- 25767505
TI  - Validation of hyperintense middle cerebral artery sign in acute ischemic stroke:
      Comparison between magnetic resonance imaging and angiography.
AB  - We performed a retrospective analysis of non-contrast computed tomography (CT)
      scans, immediately subsequent magnetic resonance imaging (MRI), and cerebral
      angiography data from 30 consecutive patients with acute ischemic stroke within 6
      hours after symptom onset. Results showed that eleven patients developed
      subsequent hemorrhagic transformation at follow-up. A hyperintense middle
      cerebral artery sign on MRI was found in six hemorrhagic patients, all of who had
      acute thrombosis formation on magnetic resonance angiography and digital
      subtraction angiography. No patients in the non-hemorrhagic group had
      hyperintense middle cerebral artery sign on MRI. The sensitivity, specificity,
      and positive predictive values of the hyperintense middle cerebral artery sign on
      MRI T1-weighted image for subsequent hemorrhagic transformation were 54.5%, 100%,
      and 100% respectively. Hyperdense middle cerebral artery sign on non-contrast CT
      was observed in nine patients, five of who developed hemorrhagic transformation.
      These data suggest that hyperintense middle cerebral artery sign on MRI T1
      weighted image is a highly specific and moderately sensitive indicator of
      subsequent hemorrhagic transformation in patients after acute ischemic stroke,
      and its specificity is superior to CT. 

PMID- 25767506
TI  - Association between AKT1 gene polymorphisms and depressive symptoms in the
      Chinese Han population with major depressive disorder.
AB  - For this study, 461 Chinese Han patients with depressive disorder were recruited.
      The AKT1 genotype and allele distribution were determined by PCR amplification
      and direct sequencing. UNPHASED software was used to analyze associations between
      the 17-item Hamilton Depression Rating Scale, total score, four factors and the
      AKT1 rs2494746 and rs3001371 polymorphisms. The results indicate that there is a
      significant association between suicidal ideation and anxiety symptoms in
      depressed patients and the rs2494746 polymorphism. The other AKT1 polymorphism,
      rs3001371, was significantly associated with work and activities. Patients with
      the rs3001371-A allele had a significantly more severe illness compared to
      patients with the rs3001371-G allele. Thus, AKT1 polymorphisms appear to be
      associated with depression severity, anxiety symptoms, work and activities, and
      suicide attempts in patients with depressive disorder. 

PMID- 25767507
TI  - Paederus beetles: the agent of human dermatitis.
AB  - BACKGROUND: Rove beetles of the genus Paederus cause dermatitis when they come in
      contact with human skin. This condition is prevalent in some tropical and
      subtropical regions, such as in northern Pakistan, where it was recorded for the
      first time by US troops. Despite much research from other countries on this
      subject, few studies, mostly clinical, have been performed in a Pakistani
      context. A survey was carried out in villages, towns and cities of Punjab
      province, Pakistan, to explore the rove beetle population dynamics and to develop
      a model to elucidate the symptoms, preventive measures and treatment strategies
      for this dermatitis. METHODS: The prospective observational and patient surveys
      were performed bimonthly over a period of two years, in different districts of
      Punjab province. Collection was carried out in fields, gardens and houses during
      every visit with the aid of a pitfall trap, light trap, flight intercept trap,
      Berlese funnel trap and sweep netting. These traps were installed for four days
      during every visit. Interviews of ten individuals of different ages and sexes
      from each site were recorded during each visit. RESULTS: Out of 980 individuals,
      26.4% were found to suffer from Paederus dermatitis. Lesions were most commonly
      found on the neck followed by the face. In July-August during the rainy season,
      this skin irritation was most prevalent and the population of these beetles
      peaked (36.2%). During May-June, the beetle population was lowest (7.85%) due to
      soil dryness. About 70% of such irritation cases were from individuals living in
      farming villages or in farmhouses. Their houses typically (80%) had broken doors
      and screen-less windows while 97% of the residents were unaware of how they may
      have come into contact with these beetles. In most cases (91% from villages/small
      towns and 24% from cities and adjoining areas) the local residents were unaware
      of modern treatment strategies. CONCLUSIONS: Paederus dermatitis is extremely
      frequent in villages with poor housing facilities and could be avoided via
      community awareness.

PMID- 25767508
TI  - Procoagulatory state in inflammatory bowel diseases is promoted by impaired
      intestinal barrier function.
AB  - Inflammatory and immune mediated disorders are risk factors for arterial and
      venous thromboembolism. Inflammatory bowel diseases (IBD) confer an even greater
      risk of thromboembolic events than other inflammatory conditions. It has been
      shown that IBD patients display defective intestinal barrier functions. Thus,
      pathogen-associated molecular patterns (PAMPs) coming from the intestinal
      bacterial burden might reach systemic circulation and activate innate immunity
      receptors on endothelial cells and platelets, promoting a procoagulative state.
      Aim of the study was to test this hypothesis, correlating the presence of
      circulating PAMPs with the activation of innate immune system and the activation
      of the coagulatory cascade in IBD patients. Specifically, we studied
      lipopolysaccharide (LPS), Toll-like receptor (TLR) 2, TLR4, and markers of
      activated coagulation (i.e., D-Dimer and prothrombin fragment F1+2) in the serum
      and plasma of IBD patients. We found that LPS levels are increased in IBD and
      correlate with TLR4 concentrations; although a mild correlation between LPS and
      CRP levels was detected, clinical disease activity does not appear to influence
      circulating LPS. Instead, serum LPS correlates with both D-Dimer and F1+2
      measurements. Taken together, our data support the role of an impairment of
      intestinal barrier in triggering the activation of the coagulatory cascade in
      IBD. 

PMID- 25767509
TI  - Gastric collision tumors: an insight into their origin and clinical significance.
AB  - Collision tumors are rare neoplasms displaying two distinct cell populations
      developing in juxtaposition to one another without areas of intermingling. They
      are rare entities with only 63 cases described in English literature. Tumors
      encountered are gastric adenocarcinomas colliding with lymphomas,
      gastrointestinal stromal tumors, squamous cell carcinomas, and neuroendocrine
      tumors. Their cell origin is obsolete by the time of diagnosis. Different
      tumorigenesis theories have been suggested to explain their behavior, yet none
      has managed to provide satisfactory explanation for all cases. Clinically they
      are indistinguishable from the dominant tumor. Lack of data does not allow
      detailed assessment of their behavior yet they seem aggressive neoplasms with
      dismal prognosis. The majority of cases have been diagnosed postoperatively
      during histologic examination of specimens. There are no guidelines or concrete
      evidence to support best way of adjuvant or other types of treatment. However,
      these rare neoplasms might help in unlocking secrets of cancer behavior including
      tumorigenesis, differentiation, and adhesion and thus clinicians should be aware
      of their existence. 

PMID- 25767510
TI  - The impact of a pure protein load on the glucose levels in type 1 diabetes
      patients treated with insulin pumps.
AB  - We aimed to estimate the impact of ingestion of a pure protein load on the
      glucose levels in T1DM patients treated with insulin pumps. We examined 10 T1DM
      patients (6 females, mean age-32.3 years, mean HbA1c-6.8%) treated with insulin
      pumps equipped with a continuous glucose monitoring system (CGMS). In Phase I,
      baseline insulin infusion was optimized to minimize the differences in fasting
      glucose levels to less than 30 mg/dL between any two time points between 9 a.m.
      and 3 p.m. In Phase II, the patients were exposed to single pure protein load.
      CGMS record was performed and the glucose pattern was defined for 6 hours of each
      phase. The maximal glucose level increment was similar for the entire duration of
      the fasting and the protein load test (26.6 versus 27.6 mg/dL, resp., P < 0.78).
      There was only a borderline difference in change between baseline versus 6th hour
      glucose (12.5 and 19.0 mg/dL, P = 0.04). Glucose variability, assessed by
      standard deviation of mean glucose levels, was 36.4 and 37.9 mg/dL, respectively
      (P = 0.01). The administration of a pure protein load does not seem to have a
      clinically significant impact on glucose levels in T1DM patients treated with
      insulin pumps. 

PMID- 25767511
TI  - Acute retinal pigment epitheliitis: spectral domain optical coherence tomography,
      fluorescein angiography, and autofluorescence findings.
AB  - A 17-year-old presented with central and paracentral scotomas in his right eye
      for one week. There was no remarkable medical or ocular history. Blood analyses
      were within normal range. At presentation both eyes' best-corrected visual
      acuities were 20/20. Slit-lamp examination result was normal. Fundus examination
      revealed yellow-white hypopigmented areas in the macula. Fluorescein angiography
      (FA) showed hypofluorescence surrounded by ring of hyperfluorescence. Fundus
      autofluorescence (FAF) was slightly increased. Spectral domain optical coherence
      tomography (SD-OCT) showed disruption of IS/OS junction with expansion of
      abnormal hyperreflectivity from retinal pigment epithelium to the outer nuclear
      layer (ONL). One month later fundus examination showed disappearance of the
      lesions. FA revealed transmission hyperfluorescence. FAF showed increased
      autofluorescence and pigment clumping. Hyperreflective band in SD-OCT
      disappeared. Loss of photoreceptor segment layers was observed in some of the
      macular lesions. The diagnosis of acute retinal pigment epitheliitis can be
      challenging after disappearance of fundus findings. FA, FAF, and SD-OCT are
      important tests for diagnosis after resolution of the disease. 

PMID- 25767512
TI  - Alkaline phosphatase in stem cells.
AB  - Alkaline phosphatase is an enzyme commonly expressed in almost all living
      organisms. In humans and other mammals, determinations of the expression and
      activity of alkaline phosphatase have frequently been used for cell determination
      in developmental studies and/or within clinical trials. Alkaline phosphatase also
      seems to be one of the key markers in the identification of pluripotent embryonic
      stem as well as related cells. However, alkaline phosphatases exist in some
      isoenzymes and isoforms, which have tissue specific expressions and functions.
      Here, the role of alkaline phosphatase as a stem cell marker is discussed in
      detail. First, we briefly summarize contemporary knowledge of mammalian alkaline
      phosphatases in general. Second, we focus on the known facts of its role in and
      potential significance for the identification of stem cells. 

PMID- 25767513
TI  - Matrix metalloproteinase 9 secreted by hypoxia cardiac fibroblasts triggers
      cardiac stem cell migration in vitro.
AB  - Cessation of blood supply due to myocardial infarction (MI) leads to complicated
      pathological alteration in the affected regions. Cardiac stem cells (CSCs)
      migration plays a major role in promoting recovery of cardiac function and
      protecting cardiomyocytes in post-MI remodeling. Despite being the most abundant
      cell type in the mammalian heart, cardiac fibroblasts (CFs) were underestimated
      in the mechanism of CSCs migration. Our objective in this study is therefore to
      investigate the migration related factors secreted by hypoxia CFs in vitro and
      the degree that they contribute to CSCs migration. We found that supernatant from
      hypoxia induced CFs could accelerate CSCs migration. Four migration-related
      cytokines were reported upregulated both in mRNA and protein levels. Upon adding
      antagonists of these cytokines, the number of migration cells significantly
      declined. When the cocktail antagonists of all above four cytokines were added,
      the migration cells number reduced to the minimum level. Besides, MMP-9 had an
      important effect on triggering CSCs migration. As shown in our results, MMP-9
      induced CSCs migration and the underlying mechanism might involve TNF-alpha
      signaling which induced VEGF and MMP-9 expression. 

PMID- 25767514
TI  - Atorvastatin and prevention of contrast induced nephropathy following coronary
      angiography.
AB  - BACKGROUND: Contrast induced nephropathy (CIN) is one of the most common
      complications after radiographic procedures using intravascular radiocontrast
      media. The aim of the current study was to assess the effect of atorvastatin on
      prevention of CIN in patients undergoing coronary angiography. MATERIALS AND
      METHODS: In a clinical trial study, 200 patients referred for angiography were
      randomly divided into two groups of using 80 mg atorvastatin and placebo before
      the procedure. Furthermore, 100 patients who were under chronic treatment of
      statins were included as the third group. Serum creatinine (Scr) levels before
      and after the procedure were evaluated and incidence of CIN (post-procedural Scr
      of >0.5 mg/dl or >25% from baseline) was assessed. RESULTS: Mean age of the
      participants was 60.06 +/- 0.69 years and 276 (92%) were male. There were no
      significant differences between group with respect to age and gender. In pre
      operation atorvastatin, placebo and long term statin groups, the incidence of CIN
      was 1%, 2% and 1%, and mean changes of Glomerular filtration rate (GFR) was 3.68
      +/- 1.32, -0.77 +/- 1.21 and 1.37 +/- 0.86; and mean changes of creatinine (Cr)
      was -0.05 +/- 0.02, 0.02 +/- 0.02 and -0.01 +/- 0.01 respectively. (P = 0.776,
      0.026 and 0.041 respectively). In pre-operation atorvastatin group, Cr decreased,
      and GFR increased significantly (P = 0.019 and 0.007 respectively). CONCLUSION:
      pre-operation short term high dose atorvastatin use was associated with a
      significant decrease in serum Cr level and increase in GFR after angiography.

PMID- 25767515
TI  - Analysis of radiation risk to patients from intra-operative use of the mobile X
      ray system (C-arm).
AB  - BACKGROUND: The aim of this study was to investigate clinical applications of
      mobile C-arms and consequent radiation risk, to increase medical attention on
      radiation protection, and to provide basic data for safe radiation use in the
      operating room. MATERIALS AND METHODS: In this study, a total of 374 surgical
      operations, conducted using a portable fluoroscopic X-ray system from January to
      March of 2013, were analyzed. Dose summaries produced by the General Electric C
      arm and data elements in digital imaging and communications in the medicine
      header of Ziehm C-arm, fluoroscopy time were used to obtain dose-area product
      (DAP) and effective dose. Corresponding mean and maximum values were calculated,
      and the resulting data on the frequency of application, fluoroscopy time, DAP,
      and effective dose were compared and analyzed in terms of surgical specialty and
      operation types. RESULTS: Orthopedic surgery was the most frequent with 165 cases
      (44.1%). The highest DAP value and effective dose were found in liver transplant
      among surgical specialty fields, with mean values of 2.90 +/- 3.76 mGy?m(2) and
      58 +/- 75.2 mSv, respectively (P = 0.0001). The highest DAP value and effective
      dose were observed in intra-operative mesenteric portography among types of
      surgery, showing mean values of 2.90 +/- 3.81 mGy?m(2) and 58.03 +/- 76.24 mSv,
      respectively (P = 0.0001). CONCLUSION: Because DAP varies significantly across
      surgical specialties and types of operation, aggressive efforts to understand the
      effects of radiation dose is critical for radiation protection from intra
      operative use of mobile C-arms.

PMID- 25767516
TI  - Pimpinella anisum in the treatment of functional dyspepsia: A double-blind,
      randomized clinical trial.
AB  - BACKGROUND: We aimed to evaluate the effects of Pimpinella anisum (anise) from
      Apiaceae family on relieving the symptoms of postprandial distress syndrome (PDS)
      in this double-blind randomized clinical trial. MATERIALS AND METHODS: Totally,
      107 patients attending the gastroenterology clinic, aged 18-65 years, diagnosed
      with PDS according to ROME III criteria and signed a written consent form were
      enrolled. They were randomized to receive either anise or placebo, blindly, for 4
      weeks. Anise group included 47 patients and received anise powders, 3 g after
      each meal (3 times/day). Control group involved 60 patients and received placebo
      powders (corn starch), 3 gafter each meal (3 times/day). The severity of
      Functional dyspepsia (FD) symptoms was assessed by FD severity scale. Assessments
      were done at baseline and by the end of weeks 2, 4 and 12. Mean scores of
      severity of FD symptoms and the frequency distribution of patients across the
      study period were compared. RESULTS: The age, sex, body mass index, smoking
      history, and coffee drinking pattern of the intervention and control groups were
      not significantly different. Mean (standard deviation) total scores of FD
      severity scale before intervention in the anise and control groups were 10.6
      (4.1) and 10.96 (4.1), respectively (P = 0.6). They were 7.04 (4.1) and 12.30
      (4.3) by week 2, respectively (P = 0.0001), 2.44 (4.2) and 13.05 (5.2) by week 4,
      respectively (P = 0.0001), and 1.08 (3.8) and 13.30 (6.2) by week 12,
      respectively (P = 0.0001). CONCLUSION: This study showed the effectiveness of
      anise in relieving the symptoms of postpartum depression. The findings were
      consistent across the study period at weeks 2, 4 and 12.

PMID- 25767517
TI  - How the anal gland orifice could be found in anal abscess operations.
AB  - BACKGROUND: On an average 30-50% of patients who undergo incision and drainage (I
      and D) of anal abscess will develop recurrence or fistula formation. It is
      claimed that finding the internal orifice of anal abscess to distract the
      corresponding anal gland duct; will decline the rate of future anal fistula.
      Surgeons supporting I and D alone claim that finding the internal opening is
      hazardous. This study is conducted to assess short-term results of optional
      method to manage patients with anal abscess and fitula-in-ano at the same time.
      MATERIALS AND METHODS: In this cross-sectional descriptive study 49 from 77
      patients with anal abscess whose internal orifice was not identified by pressing
      on the abscess, diluted hydrogen peroxide (2%) and methylene blue was injected
      into the abscess cavity and the anal canal was inspected to find out the internal
      opening. Once the opening was distinguished, an incision was given from the anal
      verge to the internal opening. RESULTS: The internal orifice was identified in 44
      out of 49 patients (90%) who underwent this new technique. Up to 18 months during
      follow-up, only 2.5% of patients with primary fistulotomy developed fistula on
      the site of a previous abscess. CONCLUSION: Conventional method to seek the
      internal orifice of anal abscesses is successful in about one-third of cases. By
      applying this new technique, surgeons would properly find the internal opening in
      >90% of patients. Needless to say, safe identification of the anal gland orifice
      in anal abscess disease best helps surgeons to do primary fistulotomy and in turn
      it would significantly decrease the rate of recurrence in anal abscess and
      fistula formation.

PMID- 25767518
TI  - Rapid diagnosis of pleural tuberculosis by Xpert MTB/RIF assay using pleural
      biopsy and pleural fluid specimens.
AB  - BACKGROUND: Early pleural tuberculosis (TB) diagnosis is particularly difficult.
      The aim of this study was to investigate the diagnostic accuracy of the Xpert
      MTB/RIF (Xpert) (Cepheid, Sunnyvale, CA) assay using pleural biopsy and pleural
      fluid specimens in patients with suspected pleural TB but who had a negative
      sputum acid-fast bacilli (AFB) smear. MATERIALS AND METHODS: In this study, 134
      sputum smear-negative suspected pleural TB patients were selected. Paired pleural
      fluid and pleural biopsy specimens were tested for Mycobacterium tuberculosis by
      standard smear-microscopy, Lowenstein-Jensen and mycobacterial growth indicator
      tube (MGIT) culture, and the Xpert assay. Mycobacterial culture from pleural
      biopsy specimens was used as a reference standard for sensitivity and specificity
      calculations. Detection of rifampicin resistance was compared with the MGIT
      method. RESULTS: Of 126 evaluable patients, 55 received a diagnosis of pleural
      TB. The sensitivity of the Xpert assay using pleural biopsy specimens for the
      diagnosis of pleural TB was 85.5%, and specificity was 97.2%. The sensitivity and
      specificity of the Xpert assay in pleural fluid were 43.6% and 98.6%,
      respectively. The Xpert assay correctly identified 90.0% of phenotypic rifampicin
      resistant cases and 93.9% of phenotypic rifampicin-susceptible cases. CONCLUSION:
      The Xpert assay on pleural biopsy specimens may provide an accurate diagnosis of
      pleural TB in patients who had a negative AFB smear.

PMID- 25767519
TI  - Does Vitamin C improve endothelial function in patients with Kawasaki disease?
AB  - BACKGROUND: Improvement of endothelial dysfunction could prevent or delay the
      occurrence of the atherosclerosis process in patients with Kawasaki disease (KD).
      It is suggested that Vitamin C could improve endothelial dysfunction. In this
      study, we investigated whether administration of Vitamin C as a water-soluble
      antioxidant could be effective in this regard among patients with KD. MATERIALS
      AND METHODS: In this case control analytic-experimental study, children aged 3-18
      years with KD, and a group of healthy children evaluated. Vitamin C (250
      mg/daily) administrated for the two studied groups for 1 month. Endothelial
      function evaluated by flow-mediated dilatation (FMD) and intima-media thickness
      (IMT) measurement using vascular Doppler ultrasonography, before and after trial.
      RESULTS: In this study, 16 patients with KD and 19 normal children were studied.
      At baseline mean of IMT and FMD was not different in the two studied groups (P >
      0.05). After Vitamin C administration IMT decreased significantly in two studied
      groups (from 27.06 +/- 6.27 to 21.56 +/- 3.77 in KD group and from 27.66 +/- 5.66
      to 23.33 +/- 3.66 in control group [P < 0.05]). FMD increased in two studied
      groups, but the difference was significant in the control group (from 6.84 +/-
      2.51 to 7.03 +/- 2.87 in KD group and from 6.53 +/- 2.36 to 7.82 +/- 2.14 in the
      control group). CONCLUSION: Vitamin C might improve the endothelial function of
      patients with KD.

PMID- 25767520
TI  - Finding of a clinical trial on symptoms and patients satisfaction under surgery
      with tissue expander with external port.
AB  - BACKGROUND: Tissue expanders are devices which are used to create enough skin to
      form suitable flap in restoration of great skin deficiencies which are not
      modified initially. The current study aimed at investigating the patients'
      satisfaction and the complications such as rupture, hematoma, wound infection,
      seroma, leakage, chronic pain, and expander expose of internal (implanted under
      the skin) and external (implanted outside) ports. MATERIALS AND METHODS: In a
      prospective quasiexperimental study conducted at Alzahra and Imam Musa al-Kadhim
      educational referral hospitals in Isfahan, two matched groups of patients each
      one contained 38 patients undergone, external and internal ports, were followed
      up weekly until the removal of expander and the injection was done weekly through
      port. The frequency of complications and patients' satisfaction between two
      groups were compared. RESULTS: The of age for patients in internal and external
      groups were 25.5 +/- 8.7 and 24.7 +/- 9, respectively (P = 0.71). There was
      significant difference between average of operation time of internal and external
      group (97.3 vs. 79.6; P < 0.001). The rate of complications such as infection,
      hematoma, skin necrosis, and expander expose between two groups was comparable,
      while significant difference was found between groups in terms of pain intensity
      in injection [4.92(1.2) vs. 1.53(0.69), P < 0.001]. There was no significant
      difference between groups in terms of symptom incidence and tissue expander
      insertion place as well as patients' satisfaction. CONCLUSION: Although internal
      port has favorite appearance; however, some complications such as skin infection
      due to frequent injection, pain rate are higher than external port lead to its
      more acceptability by the patients.

PMID- 25767521
TI  - Nutritional status, glycemic control and its associated risk factors among a
      sample of type 2 diabetic individuals, a pilot study.
AB  - BACKGROUND: The prevalence of type 2 diabetes is increasing in Malaysia, with
      most patients poorly controlled. Hence, this study aimed to determine nutritional
      and metabolic status as well as blood pressure of Malaysian patients with type 2
      diabetes mellitus and identify associated risk factors for poor glycemic control.
      MATERIALS AND METHODS: A total of 104 type 2 diabetic patients were recruited and
      completed a questionnaire covering socio-demographic status, 3-day diet records,
      and physical activity. Anthropometry and glycemic control parameters, lipid
      profile and blood pressure were also measured. RESULTS: Subjects were on average
      56.7+/-9.9 years old with a mean duration of diabetes of 6.5 +/- 5.0 years. The
      mean hemoglobin A1c of the subjects was 7.6% +/- 1.4%, with only 20.2% achieving
      the target goal of <6.5% with no significant differences between genders. The
      mean body mass index was 26.9 +/- 4.7 kg/m(2), with 86.5% either were overweight
      or obese. Only 10.6% of the subjects exercised daily. The proportions of
      macronutrients relative to total energy intake were consistent with the
      recommendations of most diabetes associations. The adjusted odds of having poor
      glycemic control were 3.235 (1.043-10.397) (P < 0.05) higher among those who had
      high density lipoprotein cholesterol levels below the normal range. Those taking
      one or two types of oral anti-diabetic drugs had 19.9 (2.959-87.391) (P < 0.01)
      and 14.3 (2.647-77.500) (P < 0.01) higher odds of poor glycemic control
      respectively compared to those who were being treated by diet alone. CONCLUSION:
      Poor glycemic control was prevalent among Malaysian diabetic patients, and this
      could be associated with low levels of HDL and being treated with oral anti
      diabetes agents.

PMID- 25767522
TI  - The effect of purslane seeds on glycemic status and lipid profiles of persons
      with type 2 diabetes: A randomized controlled cross-over clinical trial.
AB  - BACKGROUND: We are aware of limited data about the effects of purslane on
      diabetes. Earlier studies have mostly indicated the beneficial effects in animal
      models. This study aimed to evaluate the effect of purslane seeds on glycemic
      status and lipid profiles of persons with type 2 diabetes. MATERIALS AND METHODS:
      This cross-over randomized controlled clinical trial was conducted on 48 persons
      with type 2 diabetes. Participants were randomly assigned to receive either 10
      g/day purslane seeds with 240 cc low-fat yogurt (intervention group) or only 240
      cc low-fat yogurt (as a control group) for 5 weeks. After a 2-week washout
      period, subjects were moved to the alternate arm for an additional 5 weeks. At
      baseline and end of each phase of the study, fasting blood samples were collected
      to quantify plasma glucose levels, as well as serum insulin and lipid profiles.
      Within-group and between-group changes in anthropometric measures, as well as
      biochemical indicators, were compared using a paired-samples t-test. RESULTS:
      Mean age of study participants was 51.4 +/- 6.0 year. We found a significant
      reduction in weight (-0.57 vs. 0.09 kg, P = 0.003) and body mass index (-0.23 vs.
      0.02 kg/m(2), P = 0.004) following purslane seeds consumption. Despite a slight
      reduction in fasting plasma glucose levels (-2.10 vs. -2.77 mg/dL, P = 0.90), we
      failed to find any significant effect on serum insulin levels and homeostatic
      model of assessment of insulin resistance score. Furthermore, purslane
      consumption decreased serum triglyceride levels (-25.5 vs. -1.8 mg/dL, P = 0.04)
      but could not affect serum high-density lipoprotein cholesterol, low-density
      lipoprotein cholesterol, and total cholesterol levels. We observed a significant
      reduction in systolic blood pressure (-3.33 vs. 0.5 mmHg, P = 0.01) and a
      borderline significant decrease in diastolic blood pressure (-3.12 vs. -0.93
      mmHg, P = 0.09) after purslane seeds intake. CONCLUSION: In summary, consumption
      of purslane seeds for 5 weeks in persons with type 2 diabetes might improve their
      anthropometric measures, serum triglyceride levels, and blood pressure. Further
      studies are required to determine the appropriate dosage for these patients.

PMID- 25767523
TI  - Lifestyle interventions for hypertension treatment among Iranian women in primary
      health-care settings: Results of a randomized controlled trial.
AB  - BACKGROUND: Lifestyle factors such as weight, salt intake, and physical activity
      have shown to be important in treating hypertension. The object of this study was
      to describe feasibility and to assess the effectiveness of a multicomponent
      lifestyle intervention on high blood pressure (BP) of Iranian women. MATERIALS
      AND METHODS: This randomized controlled trial was conducted in four health
      centers by recruiting 161 women aged 35-65 years with high BP and randomizing
      them to a 4-week lifestyle modification (n = 80) or control group (n = 81). BP
      level and other health behavioral factors were assessed before and after the 4
      week intervention and also after 6 months. RESULTS: The mean systolic BP changed
      from 158.8 (+/-8.1) mmHg to 153.2 (+/-6.4) mmHg during 4-week and to 145.5 (+/
      4.6)) mmHg after 6 months in the intervention group (P < 0.001). There was a
      significant difference between two groups of study after 4-week mean = 5.6
      (confidence interval [CI] = 5.1-6.6) and 6 months follow mean (CI = 12.3-14.6).(P
      < 0.001) A significant correlation was detected between systolic BP (SBP) and
      diastolic BP (DBP) with weight, body mass index, waist circumference, salt
      intake, and physical activity level (P < 0.001). Stepwise regression analyses
      indicated that the weight, dietary salt intake, and physical activity level were
      significant predictors of SBP and DBP. CONCLUSION: The results of this study
      suggest that lifestyle modification program is associated with improvements in BP
      level in Iranian women.

PMID- 25767524
TI  - Relationship between craniofacial photographic analysis and severity of
      obstructive sleep apnea/hypopnea syndrome in Iranian patients.
AB  - BACKGROUND: Considering the effectiveness of craniofacial photographic analysis
      for diagnosis and management of obstructive sleep apnea-hypopnea syndrome (OSAHS)
      as well as ethnic differences in indexes measured by this method, this study
      designed to compare the surface facial dimensions, including nose width,
      intercanthal width and mandibular width of Iranian patients with mild, moderate
      and severe OSAHS. MATERIALS AND METHODS: In this cross sectional study subjects
      with mild, moderate and severe OSAHS based on apnea-hypopnea index, were studied.
      To determine cephalometric measurements, face and neck digital photographs were
      taken from participants following a standardized procedure. Cephalometric
      measurements including face, intercanthal and mandibular widths were compared
      between studied groups. RESULTS: In this study, 100 participants enrolled. From
      which 20 (20.8%), 35 (36.45%) and 41 (42.7%) of them had mild, moderate and
      severe OSAHS, respectively. Mean of nose, intercanthal and mandibular width were
      significantly higher in patients with severe OSAHS than those with mild or
      moderate OSAHS (P < 0.05). In both genders, mandibular width were higher in
      severe forms of OSAHS. Disease severity was significantly associated with
      increased age and mandibular width (P < 0.05). CONCLUSION: Mandibular width was
      the most important index, which had a significant association with the disease
      severity. It seems that our results could be used both for diagnosis and follow
      up of OSAHS management. They could be used as baseline information as well as a
      clinical and research tool in the field of OSAHS.

PMID- 25767525
TI  - Study of child language development and disorders in Iran: A systematic review of
      the literature.
AB  - Child language development and disorder in Iran has been the focus for research
      by different professions, the most prominent ones among them being psychologists
      and speech therapists. Epidemiological studies indicate that between 8% and 12%
      of children show noticeable signs of language impairment in the preschool years;
      however, research on child language in Iran is not extensive compared to studies
      in English speaking countries, which are currently the basis of clinical decision
      making in Iran. Consequently, there is no information about the prevalence of
      child language disorders in Iranian population. This review summarizes Iranian
      studies on child language development and disorder in the preschool years and
      aims to systematically find the most studied topics in the field of normal
      development, the assessment and diagnosis of language impairments as well as
      exploring the current gaps within the body of literature. Three main Iranian
      academic websites of indexed articles along with four other nonIranian databases
      were scrutinized for all relevant articles according to the inclusion criteria:
      Iranian studies within the field of Persian language development and disorders in
      preschool children published up to December 2013. They are classified according
      to the hierarchy of evidence and weighed against the criteria of critical
      appraisal of study types. As this is a type of nonintervention systematic review,
      the preferred reporting items for systematic reviews and meta-analyses is
      modified to be more compatible to the designs of eligible studies, including
      descriptive studies, test-developing and/or diagnostic studies. Several
      limitations made the process of searching and retrieving problematic; e.g., lack
      of unified keywords and incompatibility of Persian typing structure embedded in
      Iranian search engines. Overall, eligible studies met the criteria up to the
      third level of the hierarchy of evidence that shows the necessity of conducting
      studies with higher levels of design and quality. 

PMID- 25767527
TI  - Evaluation of routine postoperative chest roentgenogram for determination of the
      correct position of permanent central venous catheters tip.
AB  - BACKGROUND: Proper placement of central venous catheter (CVC) tip could reduce
      early and late catheter-related complications. Although the live fluoroscopy is
      standard of care for placement of the catheter, it is not available in many
      centers. Therefore, the present study evaluated the sensitivity and specificity
      of bedside chest X-ray (CXR) for proper positioning of the catheter tip.
      MATERIALS AND METHODS: A total of 82 adult patients undergoing elective placement
      of tunneled CVC were enrolled in this study during 2010-2012. The catheter tip
      position was evaluated by postoperative bedside chest radiographs as well as
      trans-thoracic echocardiogram as definite diagnostic tool. The catheter position
      was considered correct if the tip was positioned in the right atrium both in CXR
      or echocardiography. Finally, CXRs interpreted by expert radiologist. Thus
      findings were compared by echocardiography. Sensitivity, specificity, accuracy,
      positive, and negative predictive values were calculated. Data were analyzed
      using SPSS version 16 (SPSS Inc., Chicago, IL), and P < 0.05 considered as
      significant. RESULTS: The patients were 57.37 +/- 18.91 years of age, weighed
      65.79 +/- 15.58 kg and were 166.36 +/- 9.91 cm tall. Sensitivity and specificity
      of CXR for proper catheter tip position were 74.3% and 58.3%, respectively.
      Positive and negative predictive values were 91.2% and 28%. In addition accuracy,
      positive likelihood ratio, and negative likelihood ratio were 71.9%, 1.78, and
      2.27 respectively. CONCLUSION: Bedside CXR alone does not reliably predict
      malpositioning after CVC placement.

PMID- 25767526
TI  - Prevalence and occurrence rate of Mycobacterium tuberculosis Haarlem family multi
      drug resistant in the worldwide population: A systematic review and meta
      analysis.
AB  - BACKGROUND: Transmission of Mycobacterium tuberculosis (M. tuberculosis) can
      occur in different ways. Furthermore, drug resistant in M. tuberculosis family is
      a major problem that creates obstacles in treatment and control of tuberculosis
      (TB) in the world. One of the most prevalent families of M. tuberculosis is
      Haarlem, and it is associated with drug resistant. Our objectives of this study
      were to determine the prevalence and occurrence rate of M. tuberculosis Haarlem
      family multi-drug resistant (MDR) in the worldwide using meta-analysis based on a
      systematic review that performed on published articles. MATERIALS AND METHODS:
      Data sources of this study were 78 original articles (2002-2012) that were
      published in the literatures in several databases including PubMed, Science
      Direct, Google Scholar, Biological abstracts, ISI web of knowledge and IranMedex.
      The articles were systematically reviewed for prevalence and rate of MDR. Data
      were analyzed using meta-analysis and random effects models with the software
      package Meta R, Version 2.13 (P < 0.10). RESULTS: Final analysis included 28601
      persons in 78 articles. The highest and lowest occurrence rate of Haarlem family
      in M. tuberculosis was in Hungary in 2006 (66.20%) with negative MDR-TB and in
      China in 2010 (0.8%), respectively. From 2002 to 2012, the lowest rate of
      prevalence was in 2010, and the highest prevalence rate was in 2012. Also 1.076%
      were positive for MDR and 9.22% were negative (confidence interval: 95%).0020.
      CONCLUSION: Many articles and studies are performed in this field globally, and
      we only chose some of them. Further studies are needed to be done in this field.
      Our study showed that M. tuberculosis Haarlem family is prevalent in European
      countries. According to the presence of MDR that was seen in our results,
      effective control programs are needed to control the spread of drug-resistant
      strains, especially Haarlem family.

PMID- 25767528
TI  - Human Multidrug Resistance 1 gene polymorphisms and Idiopathic Pulmonary
      Fibrosis.
AB  - BACKGROUND: For the first time we tested an association between the human
      multidrug resistance gene 1 (MDR1) polymorphisms (SNPs) and idiopathic pulmonary
      fibrosis (IPF). Several MDR1 polymorphisms are associated with pathologies in
      which they modify the drug susceptibility and pharmacokinetics. MATERIALS AND
      METHODS: We genotyped three MDR1 polymorphisms of 48 IPF patients and 100 control
      subjects with Italian origins. RESULTS: No evidence of association was detected.
      CONCLUSION: There are 50 known MDR1 SNPs, and their role is explored in terms of
      the effectiveness of drug therapy. We consider our small-scale preliminary study
      as a starting point for further research.

PMID- 25767529
TI  - Percutaneous retrieval of an intracardiac central venous port fragment using
      snare with triple loops.
AB  - Peripherally inserted venous ports fracture with embolization in patients who
      received chemotherapy is a serious and rare complication, and few cases have been
      reported in children. We report a successful endovascular technique using a snare
      for retrieving broken peripherally inserted venous ports in a child for
      chemotherapy. Catheter fragments may cause complications such as cardiac
      perforation, arrhythmias, sepsis, and pulmonary embolism. A 12-year-old female
      received chemotherapy for acute lymphocytic leukemia through a central venous
      port implanted into her right subclavian area. The patient completed chemotherapy
      without complications 6 months ago. Venous port was accidentally fractured during
      its removal. Chest radiographs of the patient revealed intracardiac catheter
      fragment extending from the right subclavian to the right atrium (RA) and looping
      in the RA. The procedure was performed under ketamine and midazolam anesthesia
      and fluoroscopic guidance using a percutaneous femoral vein approach. A snare
      with triple loops (10 mm in diameter) was used to successfully retrieve the
      catheter fragments without any complication. Percutaneous transcatheter retrieval
      of catheter fragments is occasionally extremely useful and should be considered
      by interventional cardiologists for retrieving migrated catheters and can be
      chosen before resorting to surgery, which has potential risks related to
      thoracotomy, cardiopulmonary bypass, and general anesthesia. 

PMID- 25767530
TI  - Tuberculosis of symphysis pubis: A case report.
AB  - Symphysis pubis is an uncommon site of tuberculosis and only few cases have been
      reported in the literature. It is important to distinguish it from the more
      common entities like Osteitis pubis and Osteomyelitis of pubis symphysis to
      prevent delay in diagnosis and minimize morbidity and prevent complications. We
      report a rare case of tuberculosis of symphysis pubis in a 50-year-old Indian
      female from low socioeconomic status. Diagnosis is not difficult if one is aware
      of the condition. A high index of suspicion along with radiograph and fine needle
      aspiration led to the diagnosis. The patient had an excellent outcome following a
      complete course of anti-tuberculous chemotherapy for tuberculosis. 

PMID- 25767531
TI  - Mucinous adenocarcinoma of the appendix.

PMID- 25767532
TI  - Does disease duration influence the exercise training responses of patients with
      type 2 diabetes?

PMID- 25767533
TI  - Lessons learnt from the 2014 Ebola outbreak in West-Africa.

PMID- 25767534
TI  - Approach to neurometabolic diseases from a pediatric neurological point of view.
AB  - Objective Neurometabolic disorders are an important group of diseases that mostly
      are presented in newborns and infants. Neurological manifestations are the
      prominent signs and symptoms in this group of diseases. Seizures are a common
      sign and are often refractory to antiepileptic drugs in untreated neurometabolic
      patients. The onset of symptoms for neurometabolic disorders appears after an
      interval of normal or near normal growth and development.Additionally, affected
      children may fare well until a catabolic crisis occurs. Patients with
      neurometabolic disorders during metabolic decompensation have severe clinical
      presentation, which include poor feeding, vomiting, lethargy, seizures, and loss
      of consciousness. This symptom is often fatal but severe neurological insult and
      regression in neurodevelopmental milestones can result as a prominent sign in
      patients who survived. Acute symptoms should be immediately treated regardless of
      the cause. A number of patients with neurometabolic disorders respond favorably
      and, in some instances, dramatically respond to treatment. Early detection and
      early intervention is invaluable in some patients to prevent catabolism and
      normal or near normal neurodevelopmental milestones. This paper discusses
      neurometabolic disorders, approaches to this group of diseases (from the view of
      a pediatric neurologist), clinical and neurological manifestations, neuroimaging
      and electroencephalography findings, early detection, and early treatment. 

PMID- 25767535
TI  - Diagnostic accuracy of frozen section of central nervous system lesions: a 10
      year study.
AB  - OBJECTIVE: Definitive diagnosis of the central nervous system (CNS) lesions is
      unknown prior to histopathological examination. To determine the method and the
      endpoint for surgery, intraoperative evaluation of the lesion helps the surgeon.
      In this study, the diagnostic accuracy and pitfalls of using frozen section (FS)
      of CNS lesions is determined. MATERIALS & METHODS: In this retrospective study,
      we analyzed the results of FS and permanent diagnoses of all CNS lesions by
      reviewing reports from 3 general hospitals between March 2001 and March 2011.
      RESULTS: 273 cases were reviewed and patients with an age range from 3 to 77
      years of age were considered. 166 (60.4%) had complete concordance between FS and
      permanent section diagnosis, 83 (30.2%) had partial concordance, and 24 cases
      (9.5%) were discordant. Considering the concordant and partially concordant
      cases, the accuracy rate was 99.5%, sensitivity was 91.4%, specificity was 99.7%,
      and positive and negative predictive values were 88.4% and 99.8%, respectively.
      CONCLUSION: Our results show high sensitivity and specificity of FS diagnosis in
      the evaluation of CNS lesions. A Kappa agreement score of 0.88 shows high
      concordance for FS results with permanent section. Pathologist's
      misinterpretation, small biopsy samples (not representative of the entire tumor),
      suboptimal slides, and inadequate information about tumor location and radiologic
      findings appear to be the major causes for these discrepancies indicated from our
      study.

PMID- 25767536
TI  - Spinal Fluid Lactate Dehydrogenase Level Differentiates between Structural and
      Metabolic Etiologies of Altered Mental Status in Children.
AB  - OBJECTIVE: Altered mental status is a common cause of intensive care unit
      admission in children. Differentiating structural causes of altered mental status
      from metabolic etiologies is of utmost importance in diagnostic approach and
      management of the patients. Among many biomarkers proposed to help stratifying
      patients with altered mental status, spinal fluid lactate dehydrogenase appears
      to be the most promising biomarker to predict cellular necrosis. MATERIALS &
      METHODS: In this cross sectional study we measured spinal fluid level of lactate
      dehydrogenase in children 2 months to 12 years of age admitted to a single center
      intensive care unit over one year. Spinal fluid level of lactate dehydrogenase in
      40 pediatric cases of febrile seizure was also determined as the control group.
      RESULTS: The study group included 35 boys (58.3%) and 25 girls (41.7%). Their
      mean age was 2.7+/-3 years and their mean spinal fluid lactate dehydrogenase
      level was 613.8+/-190.4 units/liter. The control group included 24 boys (55.8%)
      and 19 girls (44.2%). Their mean age was 1.3+/-1.2 years and their mean spinal
      fluid lactate dehydrogenase level was 18.9+/-7.5 units/liter. The mean spinal
      fluid lactate dehydrogenase level in children with abnormal head CT scan was
      246.3+/-351.5 units/liter compared to 164.5+/-705.7 in those with normal CT scan
      of the head (p=0.001). CONCLUSION: Spinal fluid lactate dehydrogenase level is
      useful in differentiating structural and metabolic causes of altered mental
      status in children.

PMID- 25767537
TI  - The POLG Polyglutamine Tract Variants in Iranian Patients with Multiple
      Sclerosis.
AB  - OBJECTIVE: Multiple Sclerosis (MS) is a common disease of the central nervous
      system. The interaction between inflammatory and neurodegenerative processes
      typically results in irregular neurological disturbances followed by progressive
      disability. Mitochondrial dysfunction has been implicated in neurodegenerative
      disorders. The DNA polymerase-gamma (POLG) gene, which encodes the catalytic
      subunit of enzyme responsible for directing mtDNA replication, contains a poly
      glutamine tract (poly-Q) in the N-terminal, encoded by a CAG sequence in exon 2.
      MATERIALS & METHODS: We analyzed the POLG trinucleotide repeats in 40 Iranian
      patients with MS (27 females and 13 males with an age range of 18-55); and 47
      healthy age, gender, and ethnic matched controls were chosen by PCR-SSCP
      analysis. RESULTS: Our results indicated that the most common allele in patients
      had 10 consecutive CAG repeats (10Q). Other alleles of 11and 12 trinucleotide
      repeats were detected. We did not find any difference between the CAG repeat
      length distribution in controls and MS patients. CONCLUSION: No correlation was
      observed in the POLG gene CAG repeat with pathogenesis of MS, but it looks that
      other point mutations in POLG gene may have an important role in the disease's
      pathogenesis and produced more significant results.

PMID- 25767538
TI  - Exon deletion pattern in duchene muscular dystrophy in north west of iran.
AB  - OBJECTIVE: Duchene and Becker Muscular Dystrophy (DMD/ BMD) are x-linked
      disorders that both are the result of heterogeneous mutations in the dystrophin
      gene. The frequency and distribution of dystrophin gene deletions in DMD/ BMD
      patients show different patterns among different populations. This study
      investigates the deletion rate, type, and distribution of this gene in the Azeri
      Turk population of North West Iran. MATERIALS &METHODS: In this study, 110
      patients with DMD/ BMD were studied for intragenic deletions in 24 exons and
      promoter regions of dystrophin genes by using multiplex PCR. RESULTS: Deletions
      were detected in 63 (57.3%) patients, and around 83% localized in the mid-distal
      hotspot of the gene (on exons 44-52), 21 cases (33.3 %) with single-exon
      deletions, and 42 cases (66.6%) with multi-exonic deletions. The most frequent
      deleted exons were exon 50 (15 %) and exon 49 (14%). No deletion was detected in
      exon 3. CONCLUSION: This study suggests that the frequency and pattern of
      dystrophin gene deletions in DMD/ BMD in the Azeri Turk population of North West
      Iran occur in the same pattern when compared with other ethnic groups.

PMID- 25767539
TI  - Comparative efficacy of zonisamide and pregabalin as an adjunctive therapy in
      children with refractory epilepsy.
AB  - OBJECTIVE: Approximately one third of epileptic children are resistant to
      anticonvulsant drugs. This study evaluates the effectiveness, safety, and
      tolerability of pregabalin as adjunctive therapy in epileptic children relative
      to Zonisamide. MATERIALS & METHODS: From April 2012 to November 2012,121 children
      were referred to Mofid Children's Hospital with intractable epilepsy and enrolled
      in the study. The patients were divided into two groups (A and B) randomly. Group
      A was treated with Zonisamide and group B was treated with Pregabalin in addition
      to prior medication. We assessed seizure frequency and severity during a 4-week
      interval from the beginning of the drug treatment and compared the efficacy of
      each in these two groups. RESULTS: Group A consists of 61 patients, 26 (42.6%)
      girls, and35 (57.4%) boys with an age range from 1.5 months-14 years (mean,
      73.9+/- 44.04 months). Group B consists of 60 patients, 31(51.7%) girls, 29
      (48.3%) boys with an age range from 6 months-16 years (mean, 71+/-42.9 months).
      Age, gender, seizure onset, seizure frequency, seizure type, and previous
      antiepileptic medications showed that there was no significant difference between
      the groups (P>0.05). Zonisamide and pregabalin reduced more than 50% of seizure
      intensity in 40.2%; 45.8% of patients also had a seizure frequency decline
      between35.8-44.4%, respectively and there was no significant superiority between
      these two novel anticonvulsants (P>0.05). CONCLUSION: In this survey both
      pregabalin and Zonisamide were impressive for seizure control in children with
      intractable epilepsy and well sustained with mild complications that were
      completely reversible.

PMID- 25767540
TI  - Frequency, Causes, and Findings of Brain CT Scans of Neonatal Seizure at Besat
      Hospital, Hamadan, Iran.
AB  - OBJECTIVE: Neonatal seizures are the most common neurological symptoms and often
      signal an underlying serious neurologic condition. This study determines the
      frequency of neonatal seizure, predisposing factors, and brain computed
      tomography (CT) scan findings. MATERIALS & METHODS: In a descriptive cross
      sectional study, we evaluated all neonates with seizures who had been
      hospitalized in Besat hospital from 2007-2012. All data were gathered with
      questionnaires and used to compare with statistical tests by SPSS (ver 16).
      RESULTS: 141 (4.08%) neonates (M:F; 1:2.2) were diagnosed with neonatal seizures.
      From the total number of 3,452 neonatal hospitalization, 78% of neonates with
      seizures were less than 10 days old and 60.3% of infants were born from natural
      vaginal delivery. As the most common cause, hypoxic-ischemic encephalopathy in
      this study was associated with 31.3% (n=44) of neonatal seizures and with the
      highest mortality rate (n=6). Among admitted neonates with seizures, the overall
      mortality rate was 12.8% (18 cases). A total of 33.3% of patients (47 cases) had
      abnormal CT scan reports and 24.8% (35 cases) of patients were not evaluated with
      a CT scan. Hypoxic-ischemic encephalopathy (47%) and local ischemic changes
      (25.5%) were the most common findings in the CT scans of neonates with seizures.
      CONCLUSION: There was a significant correlation between neonatal seizures and
      delivery circumstances (p-value < 0.05). Therefore, with improvement of obstetric
      and delivery circumstances, early detection of predisposing factors and other
      rare conditions, and rapid effective treatment of these contributing factors, the
      rate of neonatal seizure in this period can be reduced.

PMID- 25767541
TI  - A comparative study of sustained attentional bias on emotional processing in ADHD
      children to pictures with eye-tracking.
AB  - OBJECTIVE: ADHD children have anomalous and negative behavior especially in
      emotionally related fields when compared to other. Evidence indicates that
      attention has an impact on emotional processing. The present study evaluates the
      effect of emotional processing on the sustained attention of children with ADHD
      type C. MATERIALS & METHODS: Sixty participants form two equal groups (each with
      30 children) of normal and ADHD children) and each subject met the required
      selected criterion as either a normal or an ADHD child. Both groups were aged
      from 6-11-years-old. All pictures were chosen from the International Affective
      Picture System (IAPS) and presented paired emotional and neutral scenes in the
      following categories: pleasant-neutral; pleasant-unpleasant; unpleasant-neutral;
      and neutral-neutral. Sustained attention was evaluated based on the number and
      duration of total fixation and was compared between the groups with MANOVA
      analysis. RESULTS: The duration of sustained attention on pleasant in the
      pleasant-unpleasant pair was significant. Bias in duration of sustained attention
      on pleasant scenes in pleasant-neutral pairs is significantly different between
      the groups. CONCLUSION: Such significant differences might be indicative of ADHD
      children deficiencies in emotional processing. It seems that the highly deep
      effect of emotionally unpleasant scenes to gain the focus of ADHD children's
      attention is responsible for impulsiveness and abnormal processing of emotional
      stimuli.

PMID- 25767542
TI  - Causes and Associated Factors of Headaches among 5 to 15-year-old Children
      Referred to a Neurology Clinic in Kashan, Iran.
AB  - OBJECTIVE: Headaches are common neurologic problems for children and adolescents.
      They are divided into two types: primary and secondary. Primary headaches include
      migraines and tension-type as well as comprise the majority of headaches. We
      detect the causes of headaches and their associations with demographic variables
      among children and adolescents. MATERIALS & METHODS: This cross-sectional study
      was performed on 5-15 year-old children with headaches from March 2010 to April
      2012 who presented at a pediatric neurology clinic in Kashan, Iran. Diagnosis of
      headaches was done in accordance with the International Classification of
      Headache Disorders. Data regarding the type of headache, age, gender, pain
      severity, aura, family history, and sleep disorder were collected. RESULTS: One
      hundred fourteen children (44 male and 70 female) with headaches were enrolled in
      the study. The types of headaches were comprised as follows: 67 cases of
      migraines, 38 cases of tension-type headaches, 2 cases of cluster headaches, and
      7 cases of secondary headaches. Pulsating headaches, family history of headaches,
      insomnia, and pain severity had higher prevalence in migrainous patients.
      CONCLUSION: Physicians should extend their information gathering about primary
      and secondary headaches. Sleep disturbances and a family history of headaches
      were the most important factors associated with migraine headaches.

PMID- 25767543
TI  - Psychometric properties of the persian version of cerebral palsy quality of life
      questionnaire for children.
AB  - OBJECTIVE: Cerebral palsy (CP) is the most common cause of chronic disability
      that restricts participation in daily life for children. Thereby, it is comprised
      of quality of life. Quality of life (QOL) measures have been a vital part of
      health outcome appraisals for individuals with CP and to obtain empirical
      evidence for the effectiveness of a range of interventions. The CP QOL-Child is a
      condition-specific QOL questionnaire designed for children with CP to assess well
      being rather than ill-being. MATERIALS & METHODS: Forward and backward
      translations of the CP QOL-Child were performed for: (1) the primary caregiver
      form (for parents of children with CP aged 4-12 years); and (2) the child self
      report form (for children with cerebral palsy aged 9-12 years). Psychometric
      properties assessment included reliability, internal consistency, and item
      discrimination, construct validity with Gross Motor Function Classification
      System (GMFCS) and Manual Ability Classification System (MACS) was done. SPSS was
      used to analyze the results of this study. RESULTS: A sample of 200 primary
      caregivers forchildren with CP (mean = 7.7 years) and 40 children (mean = 10.2
      years) completed. Internal consistency ranged from 0.61-0.87 for the primary
      caregivers form, and 0.64-0.86 for the child self-report form. Reliability ranged
      from 0.47-0.84. Item discrimination analysis revealed that a majority of the
      items (80%) have high discriminating power. Confirmatory factor analysis
      demonstrated a distinguishable domain structure as in the original English
      version. Moderate associations were found between lower QOL and more severe motor
      disability(GMFCS; r = .18-.32; p < .05 and MACS; r= .13 - .40; p < .05). The
      highest correlation between the primary caregiver and child forms on QOL was in
      the domain of functioning and consistent with the English version. CONCLUSION:
      Content validity, item discriminant validity, internal consistency, and test
      retest reliability of the Persian version of the CP QOL- Child were all
      acceptable. Further study of concurrent validity of this version is needed.

PMID- 25767544
TI  - Neural differentiation of human umbilical cord mesenchymal stem cells by
      cerebrospinal fluid.
AB  - OBJECTIVE: Wharton's jelly (WJ) is the gelatinous connective tissue from the
      umbilical cord. It is composed of mesenchymal stem cells, collagen fibers, and
      proteoglycans. The stem cells in WJ have properties that are interesting for
      research. For example, they are simple to harvest by noninvasive methods, provide
      large numbers of cells without risk to the donor, the stem cell population may be
      expanded in vitro, cryogenically stored, thawed, genetically manipulated, and
      differentiated in vitro. In our study, we investigated the effect of human
      cerebrospinal fluid (CSF) on neural differentiation of human WJ stem cells.
      MATERIAL & METHODS: The cells in passage 2 were induced into neural
      differentiation with different concentrations of human cerebrospinal fluid.
      Differentiation along with neural lineage was documented by expression of three
      neural markers: Nestin, Microtubule-Associated Protein 2 (MAP2), and Glial
      Fibrillary Astrocytic Protein (GFAP) for 21 days. The expression of the
      identified genes was confirmed by Reverse Transcriptase PCR (RT-PCR). RESULTS:
      Treatment with 100 and 200MUg/ml CSF resulted in the expression of GFAP and glial
      cells marker on days 14 and 21. The expression of neural-specific genes following
      CSF treatment was dose-dependent and time-dependent. Treatment of the cells with
      a twofold concentration of CSF, led to the expression of MAP2 on day 14 of
      induction. No expression of GFAP was detected before day 14 or MAP2 before day
      21, which shows the importance of the treatment period. In the present study,
      expression analysis for the known neural markers: Nestin, GFAP, and MAP2 using RT
      PCR were performed. The data demonstrated that CSF could play a role as a strong
      inducer. CONCLUSION: RT-PCR showed that cerebrospinal fluid promotes the
      expression of Nestin, MAP2, and GFAP mRNA in a dose-dependent manner, especially
      at a concentration of 200 MUl/ml. In summary, CSF induces neurogenesis of WJ stem
      cells that encourages tissue engineering applications with these cells for
      treatments of neurodegenerative defects and traumatic brain injury.

PMID- 25767545
TI  - Homocystinuria: Diagnosis and Neuroimaging Findings of Iranian Pediatric
      patients.
AB  - OBJECTIVE: Homocystinuria is a neurometabolic diseases characterized by symptoms
      include Neurodevelopmental delay, lens dislocation, long limbs and thrombosis.
      MATERIALS & METHODS: The patients who were diagnosed as homocystinuria marfaniod
      habits, seizure in the Neurology Department of Mofid Children's Hospital in
      Tehran, Iran between 2004 and 2014 were included in our study. The disorder was
      confirmed by clinical andneuroimaging findings along withneurometabolic and
      genetic assessment fromreference laboratory in Germany. We assessed age, gender,
      past medical history, developmental status, clinical manifestations, and
      neuroimaging findings of 20 patients with homocystinuria. RESULTS: A total of 75%
      of patients were offspring from consanguineous marriages. A total of 95% of
      patients had a history of developmental delay and 40% had developmental
      regression. A total of 75% had seizures from these 45% showed refractory
      seizures. Seizures among 13 patients werecontrolled with suitable homocystinuria
      treatment. The patients with homocystinuriawere followed for approximately 10
      years and the follow-ups showed that the patients with an early diagnosis and
      treatment had more favorable clinical responses for growth index, controlled
      refractory seizures, neurodevelopmental status, and neuroimaging findings.
      Neuroimaging findings include brain atrophy and/or white matter involvement.
      CONCLUSION: According to the results of this study, we suggest that early
      assessment and detectionplayan important role in the prevention of disease
      progression and clinical signs. Homocystinuria in patients with a positive family
      history, developmental delays, or regression, refractory, or recurrent seizures
      should take precedence over other causes.

PMID- 25767546
TI  - Beta-lactam antibiotics as a possible novel therapy for managing epilepsy and
      autism, a case report and review of literature.
AB  - Autism is a disorder of unknown etiology. There are few FDA approved medications
      for treating autism. Co-occurring autism and epilepsy is common, and glutamate
      antagonists improve some symptoms of autism. Ceftriaxone, a beta-lactam
      antibiotic, increases the expression of the glutamate transporter 1 which
      decreases extracellular glutamate levels. It is hypothesized that modulating
      astrocyte glutamate transporter expression by ceftriaxone or cefixime might
      improve some symptoms of autism. This case report of a child with autism and
      epilepsy suggests a decrease in seizures after taking cefixime. 

PMID- 25767547
TI  - Small Duplication of HPRT 1 Gene May Be Causative For Lesh-Nyhan Disease in
      Iranian Patients.
AB  - Deficiency of hypoxanthine-guanine phosphoribosyltransferase (HGPRT) is a rare
      inborn error of purine metabolism and is characterized by uric acid
      overproduction along with a variety of neurological manifestations that depend on
      a degree of the enzymatic deficiency. Inheritance of HPRT deficiency is X-linked
      recessive; thus, males are generally more affected and heterozygous females are
      carriers (usually asymptomatic). Human HPRT is encoded by a single structural
      gene on the long arm of the X chromosome at Xq26. More than 300 mutations in the
      HPRT1 gene have been detected. Diagnosis can be based on clinical and biochemical
      findings as well as enzymatic and molecular testing. Molecular diagnosis is the
      best way as it allows for faster and more accurate carrier and prenatal
      diagnosis. In this report, a new small duplication in the HPRT1 gene was found by
      sequencing, which has yet to be reported. 

PMID- 25767548
TI  - Epstein-barr virus encephalitis: a case report.
AB  - Many neurologic manifestations of Epstein-Barr virus (EBV) infection have been
      documented, including encephalitis, aseptic meningitis, transverse myelitis, and
      Guillain-Barre syndrome. These manifestations can occur alone or coincidentally
      with the clinical picture of infectious mononucleosis. EBV encephalitis is rare
      and is indicated as a wide range of clinical manifestations. We report a 10-year
      old girl presented with fever, gait disturbance, and bizarre behavior for one
      week. The results of the physical examination were unremarkable. The diagnosis of
      EBV encephalitis was made by changes in titers of EBV specific antibodies and MRI
      findings. A cranial MRI demonstrated abnormal high signal intensities in the
      basal ganglia and the striatal body, especially in the putamen and caudate
      nucleus. EBV infection should be considered when lesions are localized to the
      basal ganglia. 

PMID- 25767549
TI  - Cachexia & debility diagnoses in hospitalized children and adolescents with
      complex chronic conditions: evidence from the Kids' Inpatient Database.
AB  - OBJECTIVE: To characterize the frequency, cost, and hospital-reported outcomes of
      cachexia and debility in children and adolescents with complex chronic conditions
      (CCCs). METHODS: We identified children and adolescents (aged <=20 years) with
      CCCs, cachexia, and debility in the Kids' Inpatient Database [Healthcare Cost and
      Utilization Project, Agency for Healthcare Research & Quality]. We then compared
      the characteristics of patients and hospitalizations, including cost and duration
      of stay, for CCCs with and without cachexia and/or debility. We examined factors
      that predict risk of inpatient mortality in children and adolescents with CCCs
      using a logistic regression model. We examined factors that impact duration of
      stay and cost in children and adolescents with CCCs using negative binomial
      regression models. All costs are reported in US dollars in 2014 using Consumer
      Price Index inflation adjustment. RESULTS: We estimated the incidence of
      hospitalization of cachexia in children and adolescents with CCCs at 1,395
      discharges during the sample period, which ranged from 277 discharges in 2003 to
      473 discharges in 2012. We estimated the incidence of hospitalization due to
      debility in children and adolescents with CCCs at 421 discharges during the
      sample period, which ranged from 39 discharges in 2003 to 217 discharges in 2012.
      Cachexia was associated with a 60% increase in the risk of inpatient mortality,
      whereas debility was associated with a 40% decrease in the risk of mortality.
      Cachexia and debility increased duration of stay in hospital (17% and 39% longer
      stays, respectively). Median cost of hospitalization was $15,441.59 and
      $23,796.16 for children and adolescents with cachexia and debility, respectively.
      CONCLUSIONS: Incidence of hospitalization for cachexia in children and
      adolescents with CCCs is less than that for adults but the frequency of cachexia
      diagnoses increased over time. Estimates of the incidence of hospitalization with
      debility in children and adolescents with CCCs have not been reported, but our
      study demonstrates that the frequency of these discharges is also increasing.

PMID- 25767550
TI  - Safety and pharmacokinetics of extended use of palivizumab in Saudi Arabian
      infants and children.
AB  - BACKGROUND: The peak season of respiratory syncytial virus (RSV) infections in
      warmer climates may extend beyond the typical five-month RSV season of temperate
      regions. Additional monthly doses of palivizumab may be necessary in warmer
      regions to protect children at high risk for serious infection by the RSV.
      METHODS: In a Phase II, single-arm, single-center, non-comparative, open-label,
      prospective study conducted in Saudi Arabia, children at high risk for RSV
      infection received up to seven monthly injections of palivizumab (15 mg/kg)
      during the 2000-2001 RSV season. Key enrollment criteria were no previous
      exposure to palivizumab and gestational age <=35 weeks, <=6 months of age at
      enrollment, or chronic lung disease and <=24 months of age at enrollment. We
      wished to assess the safety, immunogenicity, and pharmacokinetics of palivizumab
      as an extended seven-dose regimen. RESULTS: Of 18 enrolled patients, 17 patients
      received seven palivizumab injections. Seven adverse events (AEs) occurred in
      five patients. Bronchiolitis was the most commonly reported AE. Six serious AEs
      occurred in four patients. No AEs were considered related to palivizumab. Trough
      levels of palivizumab in serum were >40 MUg/mL in most patients after the first
      injection and in 16/18 and 14/17 patients after the fourth and sixth injections,
      respectively. Except for one patient at one visit, the anti-palivizumab titer was
      <1:10 at all visits. CONCLUSION: These data suggest that an extended palivizumab
      regimen of up to seven monthly doses during the RSV season exhibited an
      acceptable safety profile in children at high risk for RSV infection in Saudi
      Arabia.

PMID- 25767551
TI  - Microcurrent stimulation at shenmen acupoint facilitates EEG associated with
      sleepiness and positive mood: a randomized controlled electrophysiological study.
AB  - To examine the electrophysiological effects of microcurrent stimulation at the
      Shenmen acupoint, 40 healthy normal subjects were randomly assigned to a placebo
      group (sham stimulation) and an experimental group (bilateral electrocutaneous
      stimulation at the Shenmen). The following two electroencephalographic indicators
      were used to measure brain activity. (1) Arousal level was measured with
      reference to log-transformed absolute alpha power and power source and analyzed
      using low-resolution electromagnetic tomography and (2) frontal alpha asymmetry
      was used as an indicator of mood. After real stimulation for 10 minutes, absolute
      alpha power was globally reduced in the experimental group, particularly in the
      anterior and centrotemporal regions of the brain. This indicates a decline in the
      brain activity associated with arousal. Moreover, the reduction was more
      prominent in the left frontal region, as compared to the right frontal region,
      resulting in significant increase from negative to positive frontal alpha
      asymmetry scores and reflecting an increase in the brain activity associated with
      enhanced mood. However, the placebo group exhibited no significant changes in two
      indicators after sham stimulation. This study provides initial
      electrophysiological evidence of changes in brain activity associated with
      reduced arousal (and thus greater sleepiness) and enhanced mood after
      microcurrent stimulation at the Shenmen acupoint. 

PMID- 25767552
TI  - Suppression of Inflammation and Arthritis by Orally Administrated Cardiotoxin
      from Naja naja atra.
AB  - Cardiotoxin (CTX) from Naja naja atra venom (NNAV) reportedly had analgesic
      effect in animal models but its role in inflammation and arthritis was unknown.
      In this study, we investigated the analgesic, anti-inflammatory, and
      antiarthritic actions of orally administered CTX-IV isolated from NNAV on rodent
      models of inflammation and adjuvant arthritis. CTX had significant anti
      inflammatory effects in models of egg white induced nonspecific inflammation,
      filter paper induced rat granuloma formation, and capillary osmosis tests. CTX
      significantly reduced the swelling of paw induced by egg white, the inflammatory
      exudation, and the formation of granulomas. CTX reduced the swelling of paw, the
      AA clinical scores, and pathological alterations of joint. CTX significantly
      decreased the number of the CD4 T cells and inhibited the expression of relevant
      proinflammatory cytokines IL-17 and IL-6. CTX significantly inhibited the
      secretion of proinflammatory cytokine IL-6 and reduced the level of p-STAT3 in
      FLS. These results suggest that CTX inhibits inflammation and inflammatory pain
      and adjuvant-induced arthritis. CTX may be a novel therapeutic drug for treatment
      of arthritis. 

PMID- 25767553
TI  - Inhibitory properties of aqueous ethanol extracts of propolis on alpha
      glucosidase.
AB  - The objective of the present study was to evaluate the inhibitory properties of
      various extracts of propolis on alpha-glucosidase from baker's yeast and
      mammalian intestine. Inhibitory activities of aqueous ethanol extracts of
      propolis were determined by using 4-nitrophenyl-D-glucopyranoside, sucrose and
      maltose as substrates, and acarbose as a positive reference. All extracts were
      significantly effective in inhibiting alpha-glucosidase from baker's yeast and
      rat intestinal sucrase in comparison with acarbose (P < 0.05). The 75% ethanol
      extracts of propolis (75% EEP) showed the highest inhibitory effect on alpha
      glucosidase and sucrase and were a noncompetitive inhibition mode. 50% EEP, 95%,
      EEP and 100% EEP exhibited a mixed inhibition mode, while water extracts of
      propolis (WEP) and 25% EEP demonstrated a competitive inhibition mode.
      Furthermore, WEP presented the highest inhibitory activity against maltase. These
      results suggest that aqueous ethanol extracts of propolis may be used as
      nutraceuticals for the regulation of postprandial hyperglycemia. 

PMID- 25767554
TI  - The Effect of Hydrocotyle sibthorpioides Lam. Extracts on In Vitro Dengue
      Replication.
AB  - Objective. To investigate the potential effect of Hydrocotyle sibthorpioides Lam.
      (H. sibthorpioides) extracts against in vitro dengue viral replication. Methods.
      The cytotoxicity of H. sibthorpioides was evaluated using a cell viability assay.
      Cells were pre- and posttreated with water and methanol extracts of H.
      sibthorpioides, and the viral inhibitory effect was investigated by observing the
      morphological changes, which were further confirmed by plaque assay. Results. The
      methanolic extract cytotoxicity was higher in Vero and C6/36 cells than the
      cytotoxicity of the water extract. Preincubation of the cells with H.
      sibthorpioides extract showed nonexistent to mild prophylactic effects. The
      posttreatment of Vero cells with H. sibthorpioides methanolic extract presented
      higher antidengue activities when compared with the water extract. Surprisingly,
      posttreatment of C6/36 cells resulted in an enhancement of viral replication.
      Conclusion. H. sibthorpioides had variable effects on dengue viral replication,
      depending on the treatment, cell lines, and solvent types. This study provides
      important novel insights on the phytomedicinal properties of H. sibthorpioides
      extracts on dengue virus. 

PMID- 25767555
TI  - Effects of Selected Physicochemical Parameters on Zerumbone Production of
      Zingiber zerumbet Smith Cell Suspension Culture.
AB  - Zingiber zerumbet Smith is an important herb that contains bioactive
      phytomedicinal compound, zerumbone. To enhance cell growth and production of this
      useful compound, we investigated the growth conditions of cell suspension
      culture. Embryogenic callus generated from shoot bud was used to initiate cell
      suspension culture. The highest specific growth rate of cells was recorded when
      it was cultured in liquid Murashige and Skoog basal medium containing 3% sucrose
      with pH 5.7 and incubated under continuous shaking condition of 70 rpm for 16 h
      light and 8 h dark cycle at 24 degrees C. Our results also revealed that the type
      of carbohydrate substrate, light regime, agitation speed, and incubation
      temperature could affect the production of zerumbone. Although the zerumbone
      produced in this study was not abundant compared to rhizome of Z. zerumbet, the
      possibility of producing zerumbone during early stage could serve as a model for
      subsequent improvement. 

PMID- 25767556
TI  - The effect of dietary education on ADHD, a randomized controlled clinical trial.
AB  - BACKGROUND: The purpose of this research was to study the effectiveness of the
      overall dietary intervention rather than a single nutrient on children with
      attention deficit hyperactivity disorder (ADHD). METHODS: This is a randomized
      controlled trial conducted at a child psychiatry clinic in Iran. Participants
      were 106 children and adolescents with ADHD. One group received methylphenidate
      plus dietary recommendations, while the other group only received
      methylphenidate. ADHD DSM-IV checklist was used to assess inattentiveness and
      hyperactivity/impulsivity scores at baseline and at the end of the trial.
      RESULTS: The results revealed no significant difference between the two groups
      regarding mean age, gender ratio, body mass index, baseline inattentiveness
      score, and baseline hyperactivity score. Linear regression analysis considering
      the covariant variables showed that the inattentive score at the end of the trial
      was significantly associated with the mean change of favorite diet scores.
      CONCLUSION: This is the first clinical trial examining the effect of overall
      dietary characteristics rather than a single nutrient on the children formally
      diagnosed with ADHD. According to the results, un-favorite diet had no effects on
      inattentive or hyperactivity/impulsivity score. Encouraging the children with
      ADHD to increase their intake of recommended diet markedly improves their
      attention. TRIAL REGISTRATION: The trial was registered at the Iranian Clinical
      Trials Registry (Irct ID: IRCT201311303930N29).

PMID- 25767557
TI  - Organizational Wellbeing among Workers in Mental Health Services: A Pilot Study.
AB  - INTRODUCTION: Organizational wellbeing in mental health services influences the
      outcomes of users and their families. Workers should be motivated, have a
      positive morale and be able to recognize values and the deep meaning of their
      work. This survey aims to examine the organizational wellbeing of the services
      provided by the Department of Mental Health (DSM) in Lanusei (Italy) and the
      correlations between job satisfaction and the psychosomatic health of its
      workers. MATERIALS AND METHODOLOGY: Descriptive-correlational study on a
      population of 43 mental health workers. Organizational wellbeing, as well as
      workers' job satisfaction and psychosomatic health, were measured using the
      "Multidimensional Organizational Health Questionnaire" (MOHQ). It is a self
      report questionnaire able to examine 14 dimensions of organizational wellbeing,
      14 indicators about individual discomfort, 12 indicators about individual
      wellbeing, 8 psychosomatic symptoms related to job distress. RESULTS: 31 workers
      (72%) participated in the survey. Regarding the organizational wellbeing of DSM,
      the general profile mean+/-sd was 2.66+/-0.28 (values from 1 to 4: 1=never,
      4=often). Job satisfaction was negatively correlated with headaches and
      concentration difficulties (R=-.584, p=0.001), nervousness, restlessness, anxiety
      (R=-.571, p=0.001), sense of excessive fatigue (R=-.634, p=0.000) and sense of
      depression (R=-.558, p=0.001) reported by workers. CONCLUSIONS: Data denoted an
      overall healthy state of the DSM. There were significant correlations between
      workers' job satisfaction and their psychosomatic health. The recognition and
      restitution about the weakness and strengths of the services could be useful to
      point out some organizational development perspectives.

PMID- 25767558
TI  - Flexible ACT & Resource-group ACT: Different Working Procedures Which Can
      Supplement and Strengthen Each Other. A Response.
AB  - This article is a response to Norden and Norlander's 'Absence of Positive Results
      for Flexible Assertive Community Treatment. What is the next approach?'[1], in
      which they assert that 'at present [there is] no evidence for Flexible ACT and...
      that RACT might be able to provide new impulses and new vitality to the treatment
      mode of ACT'. We question their analyses and conclusions. We clarify Flexible
      ACT, referring to the Flexible Assertive Community Treatment Manual (van
      Veldhuizen, 2013) [2] to rectify misconceptions. We discuss Norden and
      Norlander's interpretation of research on Flexible ACT. The fact that too little
      research has been done and that there are insufficient positive results cannot
      serve as a reason to propagate RACT. However, the Resource Group method does
      provide inspiration for working with clients to involve their networks more
      effectively in Flexible ACT. 

PMID- 25767559
TI  - Plant phenotyping: from bean weighing to image analysis.
AB  - Plant phenotyping refers to a quantitative description of the plant's anatomical,
      ontogenetical, physiological and biochemical properties. Today, rapid
      developments are taking place in the field of non-destructive, image-analysis 
      based phenotyping that allow for a characterization of plant traits in high
      throughput. During the last decade, 'the field of image-based phenotyping has
      broadened its focus from the initial characterization of single-plant traits in
      controlled conditions towards 'real-life' applications of robust field techniques
      in plant plots and canopies. An important component of successful phenotyping
      approaches is the holistic characterization of plant performance that can be
      achieved with several methodologies, ranging from multispectral image analyses
      via thermographical analyses to growth measurements, also taking root phenotypes
      into account. 

PMID- 25767560
TI  - Monitoring leaf water content with THz and sub-THz waves.
AB  - Terahertz technology is still an evolving research field that attracts scientists
      with very different backgrounds working on a wide range of subjects. In the past
      two decades, it has been demonstrated that terahertz technology can provide a non
      invasive tool for measuring and monitoring the water content of leaves and
      plants. In this paper we intend to review the different possibilities to perform
      in-vivo water status measurements on plants with the help of THz and sub-THz
      waves. The common basis of the different methods is the strong absorption of THz
      and sub-THz waves by liquid water. In contrast to simpler, yet destructive,
      methods THz and sub-THz waves allow for the continuous monitoring of plant water
      status over several days on the same sample. The technologies, which we take into
      focus, are THz time domain spectroscopy, THz continuous wave setups, THz quasi
      time domain spectroscopy and sub-THz continuous wave setups. These methods differ
      with respect to the generation and detection schemes, the covered frequency
      range, the processing and evaluation of the experimental data, and the mechanical
      handling of the measurements. Consequently, we explain which method fits best in
      which situation. Finally, we discuss recent and future technological developments
      towards more compact and budget-priced measurement systems for use in the field. 

PMID- 25767561
TI  - Method for 3D airway topology extraction.
AB  - In lungs the number of conducting airway generations as well as bifurcation
      patterns varies across species and shows specific characteristics relating to
      illnesses or gene variations. A method to characterize the topology of the mouse
      airway tree using scanning laser optical tomography (SLOT) tomograms is presented
      in this paper. It is used to test discrimination between two types of mice based
      on detected differences in their conducting airway pattern. Based on
      segmentations of the airways in these tomograms, the main spanning tree of the
      volume skeleton is computed. The resulting graph structure is used to distinguish
      between wild type and surfactant protein (SP-D) deficient knock-out mice. 

PMID- 25767562
TI  - Hepato-pancreato-biliary emergencies for the acute care surgeon: etiology,
      diagnosis and treatment.
AB  - Hepatopancreatobiliary (HPB) emergencies include an ample range of conditions
      with overlapping clinical presentations and diverse therapeutic options. The most
      common etiologies are related to cholelithiasis (acute cholecystitis,
      pancreatitis, and cholangitis) and non-traumatic injuries (common bile duct or
      duodenal). Although the true incidence of HPB emergencies is difficult to
      determine due to selection and reporting biases, a population-based report showed
      a decline in the global incidence of all severe complications of cholelithiasis,
      primarily based on a reduction in acute cholecystitis. Even though patients may
      present with overlapping symptoms, treatment options can be varied. The treatment
      of these conditions continues to evolve and patients may require endoscopic,
      surgical, and/or percutaneous techniques. Thus, it is essential that a
      multidisciplinary team of HPB surgeons, interventional gastroenterologists and
      radiologists are available on an as needed basis to the Acute Care Surgeon. This
      focused manuscript is a contemporary review of the literature surrounding HPB
      emergencies in the context of the acute care surgeon. The main aim of this review
      is to offer an update of the diagnosis and management of HPB issues in the acute
      care setting to improve the care of patients with potential HPB emergencies. 

PMID- 25767563
TI  - Uterine leiomyosarcoma with central nervous system metastases.
AB  - Leiomyosarcoma (LMS) is a rare tumour and comprises 2-3% of all malignant uterus
      neoplasms [1]. Leiomyosarcoma is characterised by aggressive behaviour, high
      recurrence rates, and poor overall survival, despite multimodal treatment [3].
      Surgery is the main treatment and consists of total abdominal hysterectomy. A
      randomised trial consisting of 224 patients diagnosed with uterine sarcomas stage
      I and II showed that adjuvant radiotherapy improves locoregional control. The
      role of adjuvant chemotherapy is still unclear [1]. Unfortunately, roughly 50% of
      patients with organ-confined disease will usually develop distant metastasis to
      lung, peritoneum, liver, pelvic, and para-aortic lymph nodes. Brain metastases
      are extremely rare [5]. 

PMID- 25767564
TI  - Case report of a medication error by look-alike packaging: a classic surrogate
      marker of an unsafe system.
AB  - BACKGROUND: The acronym LASA (look-alike sound-alike) denotes the problem of
      confusing similar- looking and/or sounding drugs accidentally. The most common
      causes of medication error jeopardizing patient safety are LASA as well as high
      workload. CASE PRESENTATION: A critical incident report of medication errors of
      opioids for postoperative analgesia by look-alike packaging highlights the LASA
      aspects in everyday scenarios. A change to a generic brand of medication saved
      costs of up to 16% per annum. Consequently, confusion of medication incidents
      occurred due to the similar appearance of the newly introduced generic opioid.
      Due to consecutive underdosing no life-threatening situation arose out of this
      LASA based medication error. CONCLUSIONS: Current recommendations for the
      prevention of LASA are quite extensive; still, in a system with a lump sum
      payment per case not all of these security measures may be feasible. This issue
      remains to be approached on an individual basis, taking into consideration local
      set ups as well as financial issues.

PMID- 25767565
TI  - Cost-effectiveness of clostridial collagenase ointment on wound closure in
      patients with diabetic foot ulcers: economic analysis of results from a
      multicenter, randomized, open-label trial.
AB  - BACKGROUND: Approximately 10%-15% of people with diabetes develop at least one
      foot ulcer during their lifetime. Treatment of diabetic foot ulcers (DFUs)
      represents a significant economic burden. Enzymatic debridement with clostridial
      collagenase ointment (CCO) can be used to remove necrotic tissue from wounds.
      This study examined the impact of CCO as an effective adjunct therapy to serial
      sharp debridement (SSD) and assessed the cost-effectiveness of CCO compared with
      standard DFU treatments over 1 year. METHODS: Adults 18 years or older with a
      diagnosis of type 1 or type 2 diabetes who had a neuropathic DFU were enrolled in
      a 12-week, randomized, open-label trial. Patients were randomly assigned to
      either treatment with CCO + SSD or to investigator-selected supportive care + SSD
      (Control). A 3-state Markov model with a 1-week cycle length was developed using
      wound-closure rates from the trial to estimate the number of healed-wound weeks
      and the expected DFU cost per patient. The 3 states included unhealed, healed,
      and death. Results were extrapolated to 1 year to estimate the number of healed
      wound weeks per treatment and the average cost to achieve epithelialization. The
      perspective of the analysis was that of the payer, specifically, the third party
      payer. RESULTS: The study sample included 55 patients (28 in CCO group; 27
      Control). The majority were men (74.5%) with a mean age of 57.9 years. Projected
      healing rates were greater for the CCO + SSD group compared to Control (89% vs.
      80%, respectively). The expected number of epithelialized weeks accumulated over
      1 year was 25% greater in the CCO + SSD group than for Control (35 vs. 28 weeks,
      respectively). Over a 1-year time horizon, the expected cost per DFU was greater
      in the Control group than the CCO group ($2,376 vs. $2,099, respectively). The
      estimated cost per ulcer-free week was 40% higher for Control ($85/closed-wound
      week) than for CCO + SSD ($61/closed-wound week). CONCLUSIONS: CCO + SSD therapy
      is a cost-effective method of debridement in the management of patients with
      DFUs, providing better outcomes at a lower cost. Further high quality trials are
      needed to confirm this finding. TRIAL REGISTRATION: This study was registered at
      ClinicalTrials.gov as NCT01408277.

PMID- 25767566
TI  - Predicting volume of distribution with decision tree-based regression methods
      using predicted tissue:plasma partition coefficients.
AB  - BACKGROUND: Volume of distribution is an important pharmacokinetic property that
      indicates the extent of a drug's distribution in the body tissues. This paper
      addresses the problem of how to estimate the apparent volume of distribution at
      steady state (Vss) of chemical compounds in the human body using decision tree
      based regression methods from the area of data mining (or machine learning).
      Hence, the pros and cons of several different types of decision tree-based
      regression methods have been discussed. The regression methods predict Vss using,
      as predictive features, both the compounds' molecular descriptors and the
      compounds' tissue:plasma partition coefficients (Kt:p) - often used in
      physiologically-based pharmacokinetics. Therefore, this work has assessed whether
      the data mining-based prediction of Vss can be made more accurate by using as
      input not only the compounds' molecular descriptors but also (a subset of) their
      predicted Kt:p values. RESULTS: Comparison of the models that used only molecular
      descriptors, in particular, the Bagging decision tree (mean fold error of 2.33),
      with those employing predicted Kt:p values in addition to the molecular
      descriptors, such as the Bagging decision tree using adipose Kt:p (mean fold
      error of 2.29), indicated that the use of predicted Kt:p values as descriptors
      may be beneficial for accurate prediction of Vss using decision trees if prior
      feature selection is applied. CONCLUSIONS: Decision tree based models presented
      in this work have an accuracy that is reasonable and similar to the accuracy of
      reported Vss inter-species extrapolations in the literature. The estimation of
      Vss for new compounds in drug discovery will benefit from methods that are able
      to integrate large and varied sources of data and flexible non-linear data mining
      methods such as decision trees, which can produce interpretable models. Graphical
      AbstractDecision trees for the prediction of tissue partition coefficient and
      volume of distribution of drugs.

PMID- 25767567
TI  - Smartphones in remote medicine and daily neurosurgery: The Sabah update.
AB  - INTRODUCTION: Healthcare costs continue to rise every day as the demand outgrows
      the supply of surgeons. The application of telephone consultation for immediate
      management is needed as most neurosurgeons are technology orientated. This
      enables a specialist at a remote mobile site to receive the necessary information
      and reduce transmission time, from the second the patient is seen till the
      management is obtained. MATERIALS AND METHODS: We conducted a survey on
      smartphone ownership among doctors and gathered cases that needed neurosurgical
      input from 1(st) November 2012 till 30(th) April 2013 from all 24 district
      hospitals in Sabah, Malaysia. RESULTS: The percentage of smartphone ownership
      among doctors surveyed and usage of it for remote and daily medicine at various
      departments at Queen Elizabeth Hospital, Kota Kinabalu, which shows at least 90%
      smartphone ownership and proves 100% ownership of cross-platform instant
      messaging applications and its usage for remote and daily medicine. It also
      proves to be a more popular mode of referral compared to "teleconsultation" (TC).
      DISCUSSION: In Sabah, the TC service is used for remote medical consultation and
      only available at four hospitals. The sender needs direct access to a computer
      with the TC software, and it causes delay whereas doctors using smartphones will
      just need to discuss the case on the spot and obtain the appropriate management
      within minutes. Smartphone usage is also important in daily neurosurgery
      especially at the department level to promote efficient communication,
      organization, and interaction between all the staff. As for the department's
      administrative sector, it is useful to notify if anyone is on leave, attending
      courses or even meetings as the shortage can be avoided, and redistribution
      easily done. It also allows us to transfer simple intra-departmental data at any
      time, and any place whenever required. CONCLUSION: With all the given fact, it is
      clear that a day without utilizing this service in our daily life will leave us
      handicapped and struggling with time and resources.

PMID- 25767568
TI  - Early clinical and radiographical results of keel-less and shallow keel cervical
      disc replacement.
AB  - BACKGROUND: Cervical disc replacements has been shown to be as effective as
      fusions in the treatment of radiculopathy or myelopathy due to disc prolapse.
      Newer implants were designed to reduce the difficulty of end-plate preparation.
      Since 2010, the authors have started using Discocerv (Alphatec Spine, Carlsbad,
      USA) a keel-less implant and Activ-C (B. Braun, Sheffield, UK), a shallow keel
      implant. AIM: The aim of this study was to compare the duration of surgery
      between cervical disc replacement and anterior cervical discectomy and fusion,
      and also to evaluate the functional outcome, complications, and radiographic
      outcome of cervical disc replacement. RESULTS: Fifty patients were included (20
      disc replacement and 30 fusion). This was a single surgeon retrospective study,
      with all surgery performed by the senior author (RT). The mean operation duration
      for single-level disc replacement was 2.6 h, and for single-level fusion was 2.4
      h (P = 0.4684). For 2-levels surgery, the result was 3.5 h for 2-level hybrid
      surgery (one level disc replacement and one level fusion) and 3.4 h for fusion (P
      = 0.4489). Disc replacement resulted in preservation of an average of 67% of the
      angle of motion at the sagittal plane (FFflexion-extension). The average range of
      motion after disc replacement was 6.1 degrees . The median clinical follow-up
      duration was 2 years (average 1.8 years). There was no incidence of major
      complications or significant neurovascular injury in this series of patients. A
      significant improvement in short form-36 scores was seen as early as 3 months
      postoperative (from 58 preoperative to 92 at 3 months). The improvement was
      sustained up to the fourth year of follow-up. CONCLUSION: Cervical arthroplasty
      with keel-less and shallow keel implants are safe and relatively easy to perform.
      The surgical time for disc replacement is not significantly longer than standard
      fusion surgery. There is reasonably good preservation of motion. The short-term
      functional improvement is good, and we await further long-term outcome results.
      The authors felt that cervical disc replacement will have an important role in
      the treatment of cervical degenerative disc disease in the future.

PMID- 25767570
TI  - Management of superior sagittal sinus injury encountered in traumatic head injury
      patients: Analysis of 15 cases.
AB  - BACKGROUND: Significant dural sinus injury occurs in 1.5- 5% of all head injuries
      and injury to superior sagittal sinus accounts for 70-80% of these. Its
      management is also a challenging issue to every neurosurgeon. MATERIALS AND
      METHODS: In a period of one year (Aug 2011 to july2012) out of 549 cases of head
      injuries operated in our department analysis of 15 cases (2.73%) shown to have
      superior sagittal sinus injury. Three dimensional reconstruction of skull bone
      during CT scan helped us to diagnose possible dural sinus injury pre-operatively.
      RESULTS: SSS injury was due to direct impact of fracture segment (5 cases),
      extension of fracture line over sinus area (4 cases) or due to coronal suture
      diastases (6 cases). Injury to anterior third of sagittal sinus occurred in 12
      cases (80%) and injury to middle third occurred in 3 cases (20%). Small tear over
      superior sagittal sinus was found in 7 cases (46.66%) and was managed with
      Gelfoam((r)) compression only and in two cases (13.33%) were large tear, which
      was managed with sinoraphy. In four cases (36.34%) hitch stitches over
      Gelfoam((r)) to adjacent bone given and in rest two cases (13.33%) a strip of
      bone was left over the sinus area and bilateral hitch stitches were applied.
      CONCLUSION: Injury to SSS in traumatic head injury patient though rarely
      encountered during surgery, the management is challenging to every neurosurgeon.
      Preoperative suspicion and combination of surgical techniques rather than one
      single technique may be effective in decreasing the sinus related mortality rate.

PMID- 25767569
TI  - Endoscopic endonasal trans-sphenoid management of craniopharyngiomas.
AB  - INTRODUCTION: Craniopharyngiomas treatment has been challenging because of their
      anatomical location. The endoscopic endonasal (EE) trans-sphenoidal approach is
      indicated in sellar, supra sellar, selected intraventricular lesions in adults
      and children. We are reporting our initial experience of 44 patients managed by
      EE approach. MATERIALS AND METHODS: This is a retrospective study of 44
      craniopharyngiomas. The goal of surgery was gross-total resection in all cases.
      All patients underwent pre- and post-operative comprehensive ophthalmological and
      endocrinological evaluation. Lumbar drain at the start of the operation was used
      in all cases with tumor larger than 3 cm maximum diameter. Binostril technique
      vascularized nasoseptal flap and multilayer closure of the dural defect were
      used. Wide sphenoidotomy, posterior ethmoidectomy, tuberculum selle, and planum
      removal were performed in all cases. Perioperative antibiotic prophylaxis was
      used for 72 h. RESULTS: There were 44 patients of age ranging from 8 to 65 (mean:
      42) years. Diameter of the tumor varied from 3.1 cm to 6.6 cm (average: 4.3 cm).
      Visual and pituitary dysfunctions were observed in 44 and 33, respectively,
      before surgery. Vision improvement, gross-total removal, cerebrospinal fluid
      (CSF) leak and recurrence were observed in 34, 26, four and six patients,
      respectively. Average follow-up was 19 months. CONCLUSION: Endoscopic endonasal
      trans-sphenoidal approach for craniopharyngioma is safe and effective alternative
      to transcranial approach in selected patients. Although this technique is
      associated with effective tumor removal and improved visual outcome, CSF leak,
      and endocrine dysfunctions remain a major challenge.

PMID- 25767571
TI  - One decade follow up after nucleoplasty in the management of degenerative disc
      disease causing low back pain and radiculopathy.
AB  - OBJECTIVES: Nucleoplasty is a minimally invasive procedure that is developed to
      treat patients with symptomatic, but contained disc herniations or bulging discs.
      The purpose of this study was to evaluate a decade follow-up of coblation
      nucleoplasty treatment for protruded lumbar intervertebral disc. METHODS: In this
      retrospective study there a total 50 patients who underwent intradiscal coblation
      therapy for symptomatic, but contained lumbar degenerative disc disease were
      included. Relief of low back pain, leg pain and numbness after the operation were
      assessed by visual analog pain scale (VAS). Function of lower limb and daily
      living of patients were evaluated by the Oswestry disability index (ODI) and
      subjective global rating of overall satisfaction were recorded and analyzed.
      RESULTS: There were 27 male and 23 female with followup mean follow up of 115
      months (range 105-130 months) with a mean age was 52 years (range 26-74 years).
      Analgesic consumption was reduced or stopped in 90% of these cases after 1 year.
      At 24 months follow up VAS was four points and ODI was 7.2. In three patients, we
      repeated the cool ablation after 36 months, at L3-4 level in two cases. Ten
      patients continue to be asymptomatic after 114 months of intervention. There were
      no complications with the procedure including nerve root injury, discitis or
      allergic reactions. CONCLUSIONS: Nucleoplasty may provide intermittent relief in
      contained disc herniation without significant complications and minimal
      morbidity. In accordance with the literature the evidence for intradiscal
      coablation therapy is moderate in managing chronic discogenic low back pain;
      nucleoplasty appears to be safe and effective.

PMID- 25767572
TI  - The impact of size and location on rupture of intracranial aneurysms.
AB  - OBJECTIVE: For effective management of patients with unruptured intracranial
      aneurysms, prognostic criteria for rupture, of which aneurysm size, location, and
      multiplicity are key factors. The aim of this study is to determine the
      correlation between the aneurysm size, location, and multiplicity, and their
      effect on aneurysmal rupture. MATERIALS AND METHODS: Eighty one patients with
      diagnosis of intracranial aneurysms were managed at our center from January 2008
      through July 2011. The characteristics of aneurysms, such as size, location,
      multiplicity, and presentation were retrospectively reviewed from their charts
      and radiological findings. RESULTS: Eighty one patients harboring 104 aneurysms
      were diagnosed, of them 45 were males (55.5%) and 36 were females (44.5%).
      Seventy-six patients (94%) presented with subarachnoid hemorrhage (SAH) due to
      ruptured aneurysm. Thirty-three patients who were presented with SAH (43%) had
      their ruptured aneurysm located at the anterior communicating artery with a mean
      size 5.8 mm. Most of the small (<7 mm) ruptured aneurysms were located at the
      anterior communicating artery, distal anterior cerebral arteries, posterior
      communicating arteries, and internal carotid artery bifurcation (51%, 13%, 11%,
      and 11%), respectively. There were 24 small unruptured aneurysms, 10 of them
      (42%) located at the middle cerebral arteries, while only 2 of them (8%) located
      at the anterior communicating artery. CONCLUSIONS: The aneurysm size and location
      play a substantial role in determining the risk of rupture. The most common
      location of rupture of small aneurysms was the anterior communicating artery,
      while the middle cerebral artery was the commonest site for small unrupured
      aneurysms.

PMID- 25767573
TI  - Circumferential fusion for severe post surgical cervical kyphosis.
AB  - Cervical kyphosis-though a common occurrence after surgery and other conditions
      like trauma, infections, etc., is usually restricted to around 20-40 degrees . It
      is more common in children. Angulations of more than 70-80 degrees  are
      exceedingly uncommon and present more treatment challenges. We discuss here the
      management of a 14-year-old child with a severe postoperative cervical kyphotic
      angulation of 92 degrees . The child presented 10 months after surgery for a C3
      C4 intramedullary cyst with neck deformity and near tetraplegic state. He
      underwent a combined anterior-posterior approach for correction after a trial of
      skull traction. Six months after the surgery, the child was ambulatory with
      almost total correction of the deformity. Surgical correction of postoperative
      cervical kyphosis usually involves a posterior approach for small angles and an
      anterior approach for larger angulations. The combined anterior-posterior
      approach is preferred for severe angulations or for those cases not correctable
      by a single approach. A purely posterior approach may be the only option for
      those cases where the anterior approach is impossible. 

PMID- 25767574
TI  - Brain metastasis from pancreatic cancer: A case report and literature review.
AB  - A 68-year-old man presented to our hospital with a 1-month history of slowly
      progressing altered mental status and gait disturbance. Magnetic resonance
      imaging and abdominal computed tomography revealed advanced pancreatic cancer
      (PC) with brain and para-aortic lymph node metastases. Gross total resection of
      the brain metastatic tumor was performed. Although symptoms improved, the patient
      died 3 months postoperatively. In general, the prognosis for PC patients with
      brain metastasis is very poor. Surgical resection of brain metastasis may play a
      very limited role in allowing long-term survival of patients for whom the primary
      PC is controlled or with particular oncocytic-type tumors. 

PMID- 25767575
TI  - Primary intracranial malignant melanoma: A rare casewith review of literature.
AB  - We present a rare case of the primary intracranial melanoma in the right
      parafalcine frontal region in a 65-year-old male. Computed tomography and
      magnetic resonance imaging showed a Space occupying lesion in the right
      parafalcine frontal region with necrosis, vasogenic edema and mass effect. A
      rather well-defined, dark brown-black tumor was totally removed and
      histologically diagnosed as malignant melanoma. The patient improved after
      surgery. In our case, no systemic melanomas were found in close clinical
      examinations, there was a single nodular tumor attached to the leptomeninges and
      a favorable outcome was obtained by surgical treatment alone. Primary central
      nervous system melanomas have rarely been reported, and this case is reported for
      its rarity. 

PMID- 25767576
TI  - Cervical intramedullary schwannoma mimicking a glioma.
AB  - We present a case of a cervical intramedullary schwannoma (IS), which resembled a
      glioma on radiology. Somatic and root pain, the most common presenting complaints
      of IS, were lacking in our patient, and the characteristic magnetic resonance
      finding of an enhancing thickened nerve root in IS, was absent in our case.
      Preoperative diagnosis of a cervical IS is not always possible. Complete tumor
      resection is the ideal treatment for IS. Intraoperative frozen section can be a
      useful for decision making though the tumor-cord plane will ultimately decide if
      the tumor can be radically excised. 

PMID- 25767577
TI  - Brainstem epidermoid cyst: An update.

PMID- 25767578
TI  - An outcome measure of functionality and pain in patients with low back disorder:
      A validation study of the Iranian version of Core Outcome Measures Index.
AB  - BACKGROUND: Lumbar Disc Herniation (LDH) and Lumbar Spinal Stenosis (LSS) are the
      most common diagnoses of low back and leg pain symptoms. This study aimed to
      cross-culturally translate, and validate the Core Outcome Measures Index (COMI)
      in Iran. METHODS: The translation and cross-cultural adaptation of the original
      questionnaire were performed in accordance with published guidelines. A total of
      121 patients with LDH or LSS were asked to respond to the questionnaire at two
      points in time: Pre and postoperative assessments (6 months follow-up). The
      Oswestry Disability Index (ODI) also was completed. To test the reliability, the
      internal consistency was assessed by Cronbach's alpha coefficient, and validity
      was assessed using convergent validity. Responsiveness to change also was
      assessed for comparing patients' pre and postoperative scores. RESULTS: The
      Cronbach's alpha coefficients for the COMI at pre and postoperative assessments
      ranged from 0.79 to 0.82, indicating a good internal consistency. The change in
      the ODI after surgery was strongly correlated with change in the COMI, lending
      support to its good convergent validity (r = 0.79 for LDH and r = 0.77 for LSS; P
      < 0.001). In addition, the correlation of each item with its hypothesized
      subscale of the COMI showed satisfactory results suggesting, that the items had a
      substantial association with the subscale, representing the concept. Further
      analysis also indicated that the questionnaire was responsive to change (P <
      0.0001). CONCLUSION: The Iranian version of COMI performed well, and the findings
      suggest that it is a reliable and valid measure of back pain treatment evaluation
      among LDH and lumbar canal stenosis patients.

PMID- 25767579
TI  - Posterior fossa arachnoid cysts in adults: Surgical strategy: Case series.
AB  - INTRODUCTION AND AIM: The management of posterior fossa arachnoid cyst (PFAC) in
      adults is controversial. To review our cases and literature, propose a
      practically useful surgical strategy, which gives excellent long-term outcome in
      management of PFAC. MATERIALS AND METHODS: We analyzed our case records of 26
      large intracranial arachnoid cysts in adults treated over 12 years. Of them, we
      had 7 patients with symptomatic PFAC. Reviewed the literature of 174 PFAC cases
      (1973-2012) and added 7 of our new cases with a follow-up ranging from 3 to 12
      years. RESULTS: In 6 cases the PFAC was located in the midline. In the 7(th)
      case, it was located laterally in the cerebello-pontine (CP) angle. All patients
      were treated surgically. Excision of the cyst was performed in 5 of these cases.
      Among the two intra-fourth ventricular cysts, in both the cases cysto-peritoneal
      shunt was performed. Postoperative computed tomography/magnetic resonance imaging
      showed variable decrease in size of the cyst even though clinically all patients
      improved. We propose a surgical strategy for the management of these cases which
      would aid the surgeon in decision making. DISCUSSION: We observed that these
      PFACs can occur either in the midline within the fourth ventricle or retroclival
      region or extra-fourth ventricular region. It can also develop laterally in the
      CP angle or behind the cerebellum or as intracerebellar cyst. Importance of this
      is except for Midline Intra-fourth ventricular cyst/retroclival cyst, the rest
      all can be safely excised with excellent long term outcome. The treatment
      strategy for Midline Intra-fourth ventricular cyst/retroclival cyst can be either
      cysto-peritoneal shunt or endoscopic fenestration of the cyst.

PMID- 25767580
TI  - Microsurgical management of aneurysms of the superior cerebellar artery - lessons
      learnt: An experience of 14 consecutive cases and review of the literature.
AB  - OBJECTIVE: This is a retrospective study from January 2002 to December 2012
      analyzing the results of microsurgical clipping for aneurysms arising from the
      superior cerebellar artery (SCA). MATERIALS AND METHODS: All patients with SCA
      were evaluated with computerized tomography angiography and/or digital
      subtraction angiography (DSA) prior to surgery. All patients in our series
      underwent microsurgical clipping and postoperative DSA to assess the extent of
      aneurysm occlusion. The Glasgow outcome scale (GOS) and the modified Rankin's
      scale (mRS) were used to grade their postoperative neurological status at
      discharge and 6 months, respectively. RESULTS: Fourteen patients had SCA
      aneurysms (ruptured-9, unruptured-5). There were 10 females and 4 males with the
      mean age of 47.2 years (median - 46 years, range = 24-66 years). Subarachnoid
      hemorrhage (SAH) was seen in 11 patients. The mean duration of symptoms was 2.5
      days (range = 1-7 days). The WFNS score at presentation was as follows: Grade 1
      in 10 cases, II in 2 cases, III in 1 case and IV in 1 case. In the 9 cases with
      ruptured SCA aneurysm, average size of the ruptured aneurysms was 7.3 mm (range =
      2.5-27 mm, median = 4.9 mm). The subtemporal approach was used in the first 7
      cases. The extradural temporopolar (EDTP) approach was used in the last 5 cases.
      Complications include vasospasm (n = 6), third nerve palsy (n = 5) and
      hydrocephalus (n = 3). Two patients died following surgery. At mean follow-up
      33.8 months (median - 25 months, range = 19-96 months), no patient had a rebleed.
      At discharge 9 (64%), had a GOS of 4 or 5 and 3 (21%) had a GOS of 3. At 6 months
      follow-up, 10/14 (71%) patients had mRS of 0-2, and 2 (14%) had mRS of 5.
      CONCLUSIONS: Aneurysms of the SCA are uncommon and tend to rupture even when the
      aneurysm size is small (<7 mm). They commonly present with SAH. The EDTP approach
      avoids complication caused by temporal lobe retraction and injury to the vein of
      Labbe.

PMID- 25767581
TI  - E-learning for neurosurgeons: Getting the most from the new web tools.
AB  - As open access resource, the role of Internet has been increasing in our
      professional life. There are several emergent new tools that can facilitate and
      make it more efficient to get accurate and reliable information. In this article,
      we discuss how we can manage to get the most from these new instruments, like
      blogs, Facebook, Twitter, and LinkedIn, in order to improve clinical practice.
      With good sense and some caution, these can turn to be of valuable help in our
      careers. 

PMID- 25767582
TI  - Cavernomas: Outcomes after gamma-knife radiosurgery in Iran.
AB  - BACKGROUND: Treatment of cavernomas remains a challenge in surgically
      inaccessible regions. The purpose of this study was to evaluate outcomes after
      gamma-knife surgery (GKS) for these patients. MATERIALS AND METHODS: A
      retrospective review of 100 patients treated between 2003 and 2011 was conducted
      in order to evaluate hemorrhage rates, complications, radiation effects after
      GKS. Dosage at the tumor margin was stratified into two groups: those that
      received <=13 Gy; and those who received >13 Gy. The demographic and clinical
      characteristics of patients including age, gender, and hemorrhage rates were
      extracted from care records. RESULTS: The median age was 32.5 years (ranging from
      15 to 79). 44% were female. The median follow-up time was 42.2 months (ranging
      from 24 to 90). The median volume of the lesions was 1050.0 mm(3) (ranging from
      112.0 to 4100.0) before GKS. A reduction of 27.5% in median size of cavernomas
      was achieved at the last follow-up. There was 12% treatment-related morbidity
      after GKS. The hemorrhage rate in the first 2 years after GKS was 4.1% and 1.9%
      thereafter. There was no mortality due to GKS, and 93 patients were alive at the
      last follow-up. The radiation-related complication developed with marginal dose
      13 Gy. CONCLUSION: The GKS for cavernomas appears to be a safe and beneficial in
      carefully selected patients. Low-dose GKS may be effective for the management of
      cavernous malformations.

PMID- 25767583
TI  - Medulloblastoma: A common pediatric tumor: Prognostic factors and predictors of
      outcome.
AB  - BACKGROUND: Medulloblastoma is a common malignancy in the pediatric population,
      accounting for 25% of all childhood brain tumors and relatively uncommon in
      adults. This review was to investigate treatment outcome and prognostic factors
      after treatment of medulloblastoma. MATERIALS AND METHODS: A total of 53 patients
      with histological confirmed medulloblastoma cases treated at our institute
      between 2006 and 2012 were included in the study. Demographic variables, clinical
      variables, radiological findings and treatment details with respect to age, sex,
      signs and symptoms, location of tumor, extent of surgical resection,
      histopathology type, radiotherapy dose, follow-up period and outcomes were
      recorded. Survival was analyzed by using these parameters. RESULTS: Thirty-one
      (58.5%) patients were pediatric (<14 years), and 22 (41.5%) patients were adults
      (>=14 years). Duration of symptoms were <3 months in 19 (36%) and more than 3
      months in 34 (64%) patients. Tumor resection was performed in all patients with
      gross total resection in 8 (15%) patients, near total resection in 34 (64%)
      patients and subtotal resection in 11 (21%) patients. All patients underwent
      postoperative craniospinal irradiation (CSI) delivering a median craniospinal
      dose of 36 Gy with additional boosts to the posterior fossa up to 54 Gy. Median
      overall survival was 50 months for the total group whereas 36 months for
      pediatric age group and 70 months for adult group. Desmoplastic histology showed
      an improved outcome compared with other histologies with a median survival of 71
      months compared with that of classical medulloblastoma histology being 36 months
      and other histologies shown a median survival of 34 only. CONCLUSIONS: Treatment
      of medulloblastoma with surgery and CSI yields long survival rates in both
      children and adults. Adult age group and desmoplastic histology were associated
      with a favorable outcome.

PMID- 25767584
TI  - Posterior lumbar interbody fusion and posterolateral fusion: Analogous procedures
      in decreasing the index of disability in patients with spondylolisthesis.
AB  - OBJECTIVE: The purpose of this study was to evaluate the disability in patients
      with spondylolisthesis who assigned either to posterolateral fusion (PLF) or
      posterior lumbar interbody fusion (PLIF) and to compare it between two groups.
      METHODS: In a prospective observational study, 102 surgical candidates with low
      grade degenerative and isthmic spondylolisthesis enrolled from 2012 to 2014, and
      randomly assigned into two groups: PLF and PLIF. Evaluation of disability has
      been done by a questionnaire using Oswestry Disability Index (ODI). The
      questionnaire was completed by all patients before the surgery, the day after
      surgery, after 6 months and after 1-year. RESULTS: There were no statistically
      significant differences in terms of age and sex distribution and pre-operation
      ODI between groups (P > 0.05). Comparison of the mean ODI scores of two groups
      over the whole study period showed no significant statistical difference (P =
      0.074). ODIs also showed no significant differences between two groups the day
      after surgery, 6(th) months and 1-year after surgery (P = 0.385, P = 0.093, P =
      0.122 and P = 433) respectively. Analyzing the course of ODI over the study
      period, showed a significant descending pattern for either of groups (P <
      0.0001). CONCLUSION: Both surgical fusion techniques (PLF and PLIF) were
      efficient to lessen the disability of patients with spondylolisthesis, and none
      of the fusion techniques were related to a better outcome in terms of disability.

PMID- 25767585
TI  - Role of endoscopy in multi-modality monitoring during aneurysm surgery: A single
      center experience with 175 consecutive unruptured aneurysms.
AB  - OBJECTIVE AND BACKGROUND: Unruptured aneurysm surgery is a challenge to all
      vascular neurosurgeons as the patient is asymptomatic and no even slight
      neurological deficits should be expected postoperatively. To this aim, multi
      modality checking of the vessels during the surgery is highly recommended to
      assure of the patency of the parent and perforator arteries next to an aneurysm.
      In this paper, we present our experience in the last 1.5 years with emphasis on
      the role of endoscope assisted microsurgery. METHODS: One hundred and seventy
      five patients with unruptured intracranial aneurysms were operated in our
      institute in the last 11/2 years. All patients underwent endoscope assisted
      microsurgery with pre- and post-clipping indocyanine green angiography. In
      selected cases, motor evoked potential monitoring was implemented. RESULTS: No
      mortality was observed in this period, and only 6 patients (3.4%) suffered new
      permanent neurological deficits postoperatively. Our illustrative cases show how
      endoscopy may help the surgeon to visualize hidden vessels behind and medial to
      an aneurysm. CONCLUSIONS: Our results indicated that multi-modality monitoring
      during unruptured aneurysm surgeries is associated with excellent outcome.
      Endoscope is able to show blind corners during aneurysm surgery which cannot be
      routinely observed with microscope and its application in aneurysm surgery
      assists the surgeon to make certain of complete neck clipping and preservation of
      perforating arteries around the aneurysm.

PMID- 25767586
TI  - Cervical spine fracture in a patient with ankylosing spondylitis causing a C2-T9
      spinal epidural hematoma- Treatment resulted in a rapid and complete recovery
      from tetraplegia: Case report and literature review.
AB  - Full recovery from tetraplegia is uncommon in cervical spine injury. This has not
      being reported for cervical spine fracture in a patient with ankylosing
      spondylitis causing spinal epidural hematoma. We report on a case of cervical
      spine fracture in a patient with ankylosing spondylitis who came with
      tetraplegia. He underwent a two stage fixation and fusion. He had a complete
      recovery. Two hours after the operation he regained full strength in all the
      limbs while in the Intensive Care Unit. He went back to full employment. There
      are only two other reports in the literature where patients with ankylosing
      spondylitis and extradural hematoma who underwent treatment within 12 h and
      recovered completely from tetraparesis and paraplegia respectively. Patient with
      ankylosing spondylitis has a higher incidence of spinal fracture and extradural
      hematoma. Good outcome can be achieved by early diagnosis and treatment. This can
      ensure not only a stable spine, but also a rapid and complete recovery in a
      tetraplegic patient. 

PMID- 25767587
TI  - Clear cell meningioma in a child: A case report and review of literature.
AB  - An 11-year-old boy presented with holocranial headache associated with vomiting
      and heaviness in right paranasal region. On examination, he had left sided upper
      motor neuron type facial palsy along with a subtle ipsilateral hemiparesis (grade
      4/5 Medical Research Council). Magnetic resonance imaging brain revealed a
      contrast enhancing large well-defined extra-axial mass lesion in right middle
      cranial fossa with extension into the infratemporal fossa. The mass was excised
      in two stages. Histopathology was suggestive of clear cell meningioma (CCM).
      Supratentorial pediatric CCM is a rare entity. The case is discussed along with
      review of literature on this rare clinico-pathological entity. 

PMID- 25767588
TI  - Spontaneous epidural hematoma of spine associated with clopidogrel: A case study
      and review of the literature.
AB  - Spontaneous spinal epidural hematoma (SSEH) is an uncommon neurological emergency
      which can present with the features ranging from simple back pain with
      radiculopathy to complete paraplegia or quadriplegia depending on the site and
      severity of the compression. Spinal hemorrhage associated with anti-platelet
      drugs is rarely seen. We report a case of SSEH in a 68-year-old hypertensive male
      who was on a low dose clopidogrel for secondary stroke prophylaxis and presented
      with bilateral lower limb paralysis, preceeded by severe back bain. A spinal
      magnetic resonance imaging scan was performed which revealed a posterior epidural
      hematoma of the thoraco-lumbar spine. To the best of our knowledge, not more than
      four cases of clopidogrel related spinal epidural hematoma have been reported.
      Emergent decompressive laminectomy was done within 4 hours of the presentation
      with excellent clinical outcome. Clinicians should, therefore, consider the
      remote risk of SSEH in hypertensive patients who are on anti-platelet drugs as
      early decompressive laminectomy and evacuation of the hematoma minimizes the
      permanent neurological damage. 

PMID- 25767589
TI  - Contralateral transvenous approach and embolization with 360 degrees  guglielmi
      detachable coils for the treatment of cavernous sinus dural fistula.
AB  - carotid-cavernous fistulas are spontaneours acquired connections between the
      carotid artery and the cavernous cavernous sinus, being classified as direct or
      indirect; being usually diagnosed in postmenopausal women, but are also
      associated with other pathoogies such as pregnancy, sinusitis and cavernous sinus
      thrombosis. They are clinically characterized by ophthalmological symptoms and
      pulsatile tinnitus. A 51-year-old woman who started her current condition about 4
      years ago with pulsatile tinnitus, to which were added progressively: Pain,
      conjunctival erythema, right eye proptosis and the occasional headache of
      moderate intensity. Caotid-cavernous fistula wes diagnosed, for the technical
      difficulty inherent in the case was made a contralateral transvenous approach and
      embolization with 360 degrees  GDG coils, with successful evolution of the
      patient. The endovascular management of these lesions is currently possible with
      excellent results. 

PMID- 25767590
TI  - Isolated unilateral oculomotor nerve neuropraxia following a trivial fall in a
      patient with calcified posterior petroclinoid ligament.
AB  - Isolated traumatic oculomotor nerve palsy caused by a trivial fall is extremely
      rare. We report a case of this condition. A 49-year-old woman had distal radius
      fracture and ptosis on the same side after having a trivial domestic fall. She
      did not show any clinical or radiological signs of head injury. Computerized
      tomography revealed a calcified posterior petroclinoid ligament which has direct
      anatomical and pathological relation with the oculomotor nerve. 

PMID- 25767591
TI  - Atypical craniocerebral eumycetoma: A case report and review of literature.
AB  - Craniocerebral eumycetomas are rare. They usually present with scalp swelling and
      discharging sinuses. Radiologically, they present as space-occupying lesions. We
      report a case of eumycetoma involving the left parietal cortex, bone, and
      subcutaneous tissue in a young male, farm laborer, who presented with seizures
      and blurring of vision. Imaging showed a dural based lesions enhancing moderately
      on contrast. To the best of our knowledge and belief, ours is the first published
      case in the English Literature where a eumycetoma has presented as a mass lesion
      without discharging sinuses. It is imperative to keep such atypical features of
      an infective etiology in mind because they may be one of differentials of "dural"
      based lesions where only a biopsy may suffice in the absence of significant mass
      effect to prove the diagnosis. 

PMID- 25767592
TI  - Solitary juvenile xanthogranuloma of the cervical spine in a child: A case report
      and review of literature.
AB  - The authors present a case of 15 years male child who presented with neck pain
      and progressive ascending quadriparesis. Magnetic resonance imaging showed lytic
      mass involving C5 and C6 vertebra with soft tissue extension. Surgical excision
      of mass done using anterior cervical approach. Postoperatively, patient showed
      improvement in spasticity and power. Histopathological examination of mass was
      suggestive of juvenile xanthogranuloma (JXG). At 6 months follow-up, patient was
      improving without any evidence of recurrence. Only 12 cases of JXG of spine have
      been reported till date including only four cases involving the cervical spine
      and among these four cases only two were of pediatric age group. 

PMID- 25767593
TI  - Surgical removal of the solitary metastasis of renal cell carcinoma in the third
      ventricle using an interhemispheric transcallosal trans-choroidal approach.
AB  - We herein describe a case of a solitary metastasis of renal cell carcinoma (RCC)
      in the third ventricle, which was totally removed via an interhemispheric trans
      callosal trans-choroidal approach. The histological examination revealed a
      solitary metastasis of RCC. The postoperative course was uneventful. A
      stereotactic cyber knife was additionally used for the tumor cavity. As of 2
      years after surgery, the patient has been doing well without recurrence. This
      case highlights the urgent need for an early diagnosis and surgical treatment for
      solitary metastasis of RCC to the third ventricle due to its critical course. 

PMID- 25767594
TI  - Infected epidural hematoma of the lumbar spine associated with invasive
      pneumococcal disease.
AB  - Spinal epidural abscess (SEA) and spinal epidural hematoma (SEH) are neurologic
      emergencies with distinct etiologies and treatment. Despite similarities on
      magnetic resonance imaging (MRI), their differentiation is usually possible with
      meticulous history taking and neurologic examinations. We report an unusual case
      of SEA that developed from preceding SEH, posing a diagnostic challenge to
      physicians. A 65-year-old diabetic man suddenly experienced back pain and
      weakness of both legs when he lifted heavy luggage. He was afebrile, and his
      laboratory tests were mostly unremarkable. Spinal MRI consisting of T1-weighted,
      T2-weighted, and fat-suppressed T2-weighted images revealed an epidural mass over
      the L2-L4 spinous process. He was diagnosed with SEH based on his symptoms and
      MRI findings, and was treated conservatively using steroid pulse therapy. Despite
      initial improvement, he suddenly developed into septic shock and coma on the
      10(th) hospital day, and died shortly thereafter. An autopsy revealed massive pus
      accumulation in the lumbar epidural space and brain, and a postmortem diagnosis
      of infected SEH associated with invasive pneumococcal disease was established.
      Serial MRI studies, including diffusion-weighted and/or gadolinium-enhanced T1
      weighted images are warranted in patients with a presumed diagnosis of SEH
      receiving steroid therapy to detect such infectious transformation. 

PMID- 25767595
TI  - Refractory hypokalemia during barbiturate coma therapy used for treating
      refractory intracranial hypertension in traumatic brain injury.
AB  - Barbiturate coma therapy (BCT) is a choice treatment for refractory intracranial
      hypertension after all surgical or medical managements have failed to control the
      intracranial pressure (ICP). It helps to reduce cerebral blood flow, cerebral
      metabolic rate of oxygen consumption and ICP. However, this therapy can also
      cause many complications. One of the underreported, but life-threatening
      complications is refractory hypokalemia, which can lead to subsequent rebound
      hyperkalemia after sudden cessation. We report our experience of managing unusual
      complication of refractory hypokalemia during BCT with thiopentone in
      postdecompressive craniectomy patient. 

PMID- 25767596
TI  - Metachronous spinal metastases from supratentorial anaplastic astrocytoma.
AB  - Leptomeningeal spinal metastases from supratentorial high-grade glioma are
      relatively rare. Authors report an unusual case of metachronous, symptomatic,
      dual spinal drop metastases in a 20-year-old male patient who was operated for
      right insular anaplastic astrocytoma 20 months earlier. Surgical decompression of
      the symptomatic D11-L2 drop metastasis was carried out. Histo-pathological
      examination revealed features suggestive of glioblastoma multiforme. Patient was
      advised postoperative radiotherapy. The pertinent literature is reviewed
      regarding this uncommon entity. 

PMID- 25767597
TI  - Pan ventricular neurocytoma.
AB  - Central neurocytomas are intraventricular benign neoplasms located within the
      lateral ventricle adjacent to foramen of Monro. A rare case of a central
      neurocytoma extending throughout the entire ventricular system at the time of
      presentation is reported. The clinical course of this tumor in a 25-year-old male
      and its management are presented with relevant review of the literature. 

PMID- 25767598
TI  - Orbital intraconal abducens nerve schwannoma: A case report and review of the
      literature.
AB  - Authors report a case of right orbital intraconal abducens nerve schwannoma in a
      32-year lady, who presented with a sense of tightness and discomfort in right eye
      on looking extreme right side since 4 months. The tumor was totally excised with
      functional preservation of the nerve by superior orbitotomy. The clinical,
      radiological features and the management are discussed. 

PMID- 25767599
TI  - Association between CYP1A1 Ile462Val Polymorphism and Oral Squamous Cell
      Carcinoma Susceptibility: Evidence from 13 Investigations.
AB  - CYP1A1 Ile462Val polymorphism might play a key role in pathogenesis of oral
      squamous cell carcinoma (OSCC). Many case-control studies have investigated the
      association between CYP1A1 Ile462Val polymorphism and OSCC susceptibility.
      However, the conclusions are inconsistent. To aim a convincible conclusion, we
      carried out a meta-analysis to systematically evaluate the association of CYP1A1
      Ile462Val polymorphism with OSCC susceptibility. We searched Pubmed, Web of
      Science, Ovid and Embase databases for available publications. The odds ratio
      (OR) with the corresponding 95% confidence interval (95% CI) was carried out to
      estimate the association. A total of 13 papers including 1468 cases and 2183
      controls were included, a significant increased OSCC risk was observed in
      recessive model (OR=1.64, 95% CI=1.08-2.49), but not other genetic models. Our
      results suggest that the homozygous variant of CYP1A1 Ile462Val might be a risk
      factor of OSCC. 

PMID- 25767600
TI  - Association of Body Mass Index Changes during Neoadjuvant Chemotherapy with
      Pathologic Complete Response and Clinical Outcomes in Patients with Locally
      Advanced Breast Cancer.
AB  - The purpose of this study was to determine the association between body mass
      index (BMI) measurements (baseline BMI and changes in BMI during neoadjuvant
      systemic treatment [NST]) and clinical efficacy (pathologic complete response
      [pCR] rate and survival outcomes) in locally advanced breast cancer (LABC). We
      hypothesized that high baseline BMI and increases in BMI during NST are
      associated with lower pCR rates and poorer clinical outcomes in LABC. We
      retrospectively reviewed the medical records of 1002 patients, 204 with primary
      inflammatory breast cancer (IBC) and 798 with stage III non-IBC, who underwent
      standard NST and definitive surgery between November 1, 2006, and December 31,
      2012. The median follow-up time for the survivors was 19.6 months (0.4 - 67.8
      months). The pCR rates of patients whose BMI increased or decreased were 23.2%
      and 18.1%, respectively, (p=0.048). The unadjusted overall survival (OS) was
      significantly better in the group with increased BMI (p=0.006). However,
      increased BMI was not an independent predictor of pCR and clinical outcomes
      (recurrence-free survival and OS) after adjusting for other clinical variables.
      In subset analyses, increased BMI as a continuous variable was an independent
      predictor of higher pCR rates in the normal BMI/underweight group (odds ratio
      [OR]=1.35, 95% confidence interval [CI]: 1.06-0.71, p=0.015). Increased BMI (BMI
      change >=0 vs. <0) was also an independent predictor of pCR (OR=1.65, 95% CI:
      1.00-2.72, p=0.049) in the postmenopausal group. Our results show that increasing
      BMI shows improved clinical outcome in terms of better pCR rates in normal
      BMI/underweight group and in the postmenopausal group. These results contradict
      previously reported findings on the association between high BMI and poor
      clinical efficacy regarding pCR rate and survival outcomes in early-stage breast
      cancer. Thus, the role of BMI in breast cancer may depend on patients' clinical
      characteristics such as advanced stage. 

PMID- 25767601
TI  - YSY01A, a Novel Proteasome Inhibitor, Induces Cell Cycle Arrest on G2 Phase in
      MCF-7 Cells via ERalpha and PI3K/Akt Pathways.
AB  - Given that the proteasome is essential for multiple cellular processes by
      degrading diverse regulatory proteins, inhibition of the proteasome has emerged
      as an attractive target for anti-cancer therapy. YSY01A is a novel small molecule
      compound targeting the proteasome. The compound was found to suppress viability
      of MCF-7 cells and cause limited cell membrane damage as determined by
      sulforhodamine B assay (SRB) and CytoTox 96((r)) non-radioactive cytotoxicity
      assay. High-content screening (HCS) further shows that YSY01A treatment induces
      cell cycle arrest on G2 phase within 24 hrs. Label-free quantitative proteomics
      (LFQP), which allows extensive comparison of cellular responses following YSY01A
      treatment, suggests that various regulatory proteins including cell cycle
      associated proteins and PI3K/Akt pathway may be affected. Furthermore, YSY01A
      increases p-CDC-2, p-FOXO3a, p53, p21(Cip1) and p27(Kip1) but decreases p-Akt, p
      ERalpha as confirmed by Western blotting. Therefore, YSY01A represents a
      potential therapeutic for breast cancer MCF-7 by inducing G2 phase arrest via
      ERalpha and PI3K/Akt pathways. 

PMID- 25767602
TI  - Induction of BCL2-Interacting Killer, BIK, is Mediated for Anti-Cancer Activity
      of Curcumin in Human Head and Neck Squamous Cell Carcinoma Cells.
AB  - Naturally occurring diarylheptanoid curcumin (CUR), a principal component of the
      Asian spice turmeric, has been shown to have anti-cancer effects in many tumor
      types. However, a detailed mechanism regarding CUR induced tumor cell killing
      remain to be comprehensively explored. Using two head neck squamous cell
      carcinoma (HNSCC) cell lines FaDu (hypopharyngeal) and Cal27 (tongue), we
      demonstrated a novel mechanism by which CUR levies the cytotoxic effect. We found
      that CUR induced upregulation of pro-apoptotic Bik, down-regulation of survival
      signaling by AKT and NF-kappaB prior to the induction of the caspase-cascade
      reduction of cell proliferation, are primary mechanisms of CUR-induced cell
      death, thus providing insights into the anti-tumor activity of CUR in HNSCC
      cells. 

PMID- 25767603
TI  - Expression and Splice Variant Analysis of Human TCF4 Transcription Factor in
      Esophageal Cancer.
AB  - OBJECTIVE: The human T cell transcription factor-4 (TCF4) interacts functionally
      with beta-catenin in the Wnt signaling pathway, whose deregulation is involved in
      the tumorigenesis of various types of cancers. Recent studies showed that TCF4
      mRNAs were subject to alternative splicing, which was proposed to be important in
      regulating transactivational properties of the corresponding protein isoforms.
      Here we investigated the splicing isoforms and the roles of TCF4 in human
      esophageal squamous cell carcinoma. METHODS: RT-PCR and subsequent cloning and
      sequencing were applied to identify the splicing isoforms. Western blotting and
      realtime PCR were used to analyze the expression of TCF4. Knockdown of TCF4 was
      achieved with siRNA and stable transfection of expression vectors was performed.
      RESULTS: Our results showed there were a lot of different isoforms of TCF4 mRNA
      both in human esophageal cancers and cell line. Further, knockdown of TCF4E
      isoform expression in EC109 cells inhibited the cell growth, while overexpression
      of TCF4M isoform did not alter its transcription activity. Moreover, sixteen
      potential binding proteins of TCF4 were preliminarily identified by mass
      spectrometry. CONCLUSIONS: Our data suggested that deregulation of TCF4 isoforms
      may contribute to the tumorigenesis of ESCC.

PMID- 25767604
TI  - Grainyhead-like 2 Promotes Tumor Growth and is Associated with Poor Prognosis in
      Colorectal Cancer.
AB  - GRHL2 was implicated in regulating cancer development. Our previous study
      demonstrated that knockdown GRHL2 in colorectal cancer (CRC) cells inhibited cell
      proliferation by targeting ZEB1. It is unclear whether GRHL2 expression may have
      diagnostic or prognostic value in colorectal carcinoma. Additionally, how GRHL2
      is associated with the clinical features of colorectal carcinoma is not known. In
      current study, immunohistochemistry stains were performed to examine GRHL2 in 171
      colorectal cancers and paired normal colon mucosa. The prognostic value of GRHL2
      was investigated in a retrospective cohort study with a five-year follow-up. The
      effects of GRHL2 on cell growth in vitro and in vivo were explored by GRHL2 over
      expressing in HT29 and SW620 CRC cells. Further, the regulation of cell cycle and
      proliferation proteins by GRHL2 were assessed by flow cytometry and western blot.
      We found that GRHL2 was over-expressed in CRC tissues, and played an important
      role in CRC tumorigenesis. GRHL2 expression positively correlated with tumor size
      and TNM stage. Kaplan-Meier analysis showed that GRHL2 was an independent
      prognostic factor for both overall survival and recurrence-free survival. Ectopic
      over-expression of GRHL2 in CRC cell line HT29 and SW620 induced an increase of
      cellular proliferation in vitro and promoting tumor growth in vivo. The
      acquisition of GRHL2 regulated cell cycle and modulates the expression of
      proliferation proteins p21, p27, cyclin A and cyclin D1. Together, our findings
      reveal GRHL2 can be used as a novel predictive biomarker and represent a
      potential therapeutic target against CRC. 

PMID- 25767605
TI  - Expression and Function of HAX-1 in Human Cutaneous Squamous Cell Carcinoma.
AB  - HAX-1 is an anti-apoptotic factor and overexpressed in many types of cancers.
      However, the functional role of HAX-1 in human cutaneous squamous cell carcinoma
      (cSCC) remains unclear. Our aim was to investigate the expression of HAX-1 in
      cSCC and its relationship with the development of cSCC. HAX-1 expression in cSCC
      tissues and in-vitro cell models were evaluated by real-time quantitative PCR (RT
      qPCR), Western blot and immunohistochemistry. And the RNAi strategy was used to
      observe the relationship of HAX-1 and cSCC in A431 cells. The mRNA and protein
      level of HAX-1 were significantly higher in cSCC compared with normal tissue.
      There were significant differences in thickness (P=0.014), differentiation
      (P=0.027) and TNM stages (P=0.007). After knockdown the expression of HAX-1 by
      siRNA, the proliferation and the motility of A431 cell was inhibited obviously,
      and the apoptosis of A431 cells were induced too. HAX-1 may be a risk factor for
      patients with cSCC. As a potential tumor promoter in cSCC, HAX-1 may be a novel
      potential therapeutic target for cSCC treatment and deserves further
      investigation. 

PMID- 25767606
TI  - Could Somatostatin Enhance the Outcomes of Chemotherapeutic Treatment in SCLC?
AB  - PURPOSE: Somatostatin is a peptide with a potent and broad antisecretory action,
      which makes it an invaluable drug target for the pharmacological management of
      pituitary adenomas and neuroendocrine tumors. Furthermore, somatostatin (SST)
      receptors (SSTR1, 2A and B, 3, 4 and 5) belong to the G protein coupled receptor
      family and are overexpressed in tumors. Since, human small-cell lung cancer
      overexpresses somatostatin receptors (STTR), they could be legitimate targets for
      treating SCLC.The aim of this study was the evaluation of cytotoxicity of
      somatostatin in combination with several anticancer drugs in HTB-175 cell line
      (Small Cell Lung Cancer Cell line that expresses neuron specific enolase).
      METHODS: Docetaxel, Paclitaxel, Carboplatin, Cisplatin, Etoposide, Gemzar,
      Navelbine, Fluorouracil, Farmorubicin are the chemotherapeutic drugs that we used
      for the combination before and after adding somatostatin in SCLC cell culture.
      HTB-175 cell line was purchased from ATCC LGC Standards.At indicated time-point,
      48h after the combination, cell viability and apoptosis were measured with
      Annexin V staining by flow cytometry. RESULTS: Flow cytometry showed that
      Docetaxel, Paclitaxel, Gemzar and Cisplatin induced apoptosis more when they were
      added before somatostatin, whereas etoposide induced apoptosis more after
      somatostatin treatment. Navelbine alone or in combination with somatostatin
      showed no differences in apoptosis. Farmorubicin showed equal toxicity in all
      combinations. Fluorouracil and Carboplatin induced apoptosis more when added
      alone in HTB-175 cell line. However, increased apoptosis was also observed when
      Carboplatin was administered before somatostatin in higher concentrations.
      CONCLUSION: Our results indicated that depending on the drug, somatostatin
      treatment before or after chemotherapeutic drugs increased apoptosis in small
      cell lung cancer cells. We suggest that long acting somatostatin analogues could
      be used as additive and maintenance therapy in combination to antineoplastic
      agents in SCLC patients.

PMID- 25767607
TI  - Clinical Significance of Female-hormones and Cytokines in Breast Cancer Patients
      Complicated with Aromatase Inhibitor-related Osteoarthropathy - Efficacy of
      Vitamin E.
AB  - INTRODUCTION: Aromatase inhibitor use for postmenopausal hormone-sensitive breast
      cancer patients often results in drug-induced osteoarthropathy, while its
      accurate mechanism has not been clarified. We investigated the implication of
      female hormones and several cytokines in osteoarthropathy complicated with
      aromatase inhibitor treatment, and the efficacy of vitamin E on the severity of
      osteoarthropathy, in breast cancer patients. METHODS: Sixty two breast cancer
      patients treated with aromatase inhibitor for average of 1.77 years were
      included. These patients were orally administered vitamin E (150mg/day) for 29.8
      days to alleviate aromatase inhibitor-related osteoarthropathy. Severity of
      osteoarthropathy was scored, and the patients were grouped based on the severity
      or vitamin E efficacy. Serum estradiol, progesterone, vitamin E, interferon-gamma
      (IFN-gamma), tumor necrosis factor-alpha (TNF-alpha), IL-2, IL-4, IL-6, IL-10,
      and IL-17A concentrations were measured by ELISA or beads array procedures
      followed by flow cytometry. RESULTS: There was no significant difference in serum
      concentrations of the biomarkers between the severe and the mild osteoarthropathy
      groups before vitamin E administration. The osteoarthropathy scores significantly
      decreased after vitamin E administration (p=0.0243), while serum-estradiol
      concentrations did not change. The serum-estradiol concentrations before vitamin
      E administration in the group sensitive to the vitamin E efficacy were
      significantly lower, as compared with those in the insensitive group (p=0.0005).
      The rate of the highly sensitive patients to the vitamin E efficacy in those
      exhibiting low serum-estradiol concentrations was significantly higher than that
      in the high serum-estradiol group (p=0.0004). In the sensitive group, serum
      estradiol concentrations after taking vitamin E were significantly higher than
      those before taking vitamin E (p=0.0124). CONCLUSIONS: Vitamin E administration
      seemed to be a potential way for relieving osteoarthropathy complicated with
      aromatase inhibitor use. Using serum-estradiol concentration, it would be
      possible to select out the breast cancer patients who will respond well to the
      vitamin E therapy for osteoarthropathy complicated with aromatase inhibitor.

PMID- 25767608
TI  - Tailoring Pelvic Lymphadenectomy for Patients with Stage IA2, IB1, and IIA1
      Uterine Cervical Cancer.
AB  - PURPOSE: The purpose of this study was to assess the risk factors for pelvic
      lymph node metastasis (PLNM) in patients with early-stage uterine cervical
      cancer. METHODS: A total of 192 patients with early-stage uterine cervical cancer
      (FIGO stage IA2, IB1, and IIA1) receiving radical hysterectomy with pelvic
      lymphadenectomy were included in the statistical analysis. RESULTS: Thirty-six
      patients (18.8%) developed PLNM, and the incidences of PLNM in patients with
      stage IA2, stage IB2, and stage IIA1 were 0% (0/6), 13.9% (20/144), and 38.1%
      (16/42), respectively. The most common location of PLNM was the obturator lymph
      node. Univariate analysis showed that stage IIA1 (p < 0.001), tumor size greater
      than 3 cm (p = 0.019), deep-full thickness stromal invasion (p < 0.001), and
      lymphovascular invasion (p = 0.001) were associated with PLNM. Multivariate
      analysis showed that deep or full-thickness stromal invasion and lymphovascular
      invasion were significantly and independently associated with PLNM (p < 0.05 for
      both). The incidence of PLNM was 34.9% and 28.7% in patients with deep-full
      thickness stromal invasion and lymphovascular invasion, respectively, but that
      was only 5.7% and 9.2% in patients with superficial-middle stromal invasion and
      absence of lymphovascular invasion, respectively. CONCLUSION: Patients with
      superficial-middle stromal invasion and without lymphovascular invasion may be
      avoided pelvic lymphadenectomy in stage IA2, IB1, IIA1 uterine cervical cancer.

PMID- 25767609
TI  - The Effect of Tumor Microenvironment on Autophagy and Sensitivity to Targeted
      Therapy in EGFR-Mutated Lung Adenocarcinoma.
AB  - Lung cancer is the top cancer killer worldwide. Tyrosine kinase inhibitors
      (TKIs), for example erlotinib, are commonly used to target epidermal growth
      factor receptor (EGFR)-mutated lung adenocarcinoma (ADC). Autophagy is a cellular
      response to stress, serving as a protective mechanism during anticancer therapy.
      The tumor microenvironment (TME) is composed of non-tumor cells that include
      fibroblasts. Our study aimed to investigate the effect of TME on autophagy and
      TKI sensitivity. Following cell sorting after direct co-culturing, autophagy and
      cytokine production were observed in both HCC827 and MRC-5 cells. The synergistic
      combination of erlotinib and chloroquine (autophagy inhibitor) was observed under
      TME. Tumor growth was significantly suppressed with combined
      erlotinib/chloroquine compared with erlotinib in HCC827 xenografts. 

PMID- 25767610
TI  - Comparison of RECIST 1.0 and RECIST 1.1 in Patients with Metastatic Cancer: A
      Pooled Analysis.
AB  - BACKGROUND: We conducted this pooled analysis to investigate the impact of RECIST
      1.1 on the selection of target lesions and classification of tumor response, in
      comparison with RECIST 1.0. Methods : We searched MEDLINE and EMBASE for articles
      with terms of RECIST 1.0 or RECIST 1.1. We looked into all abstracts and virtual
      meeting presentations from the conferences of ASCO and ESMO between 2009 and
      2013. RESULTS: There were six articles in the literature comparing the clinical
      impacts of RECIST 1.0 and RECIST 1.1 in patients with metastatic cancer. A total
      of 359 patients were recruited from the six trials; 217 with non-small cell lung
      cancer, 61 with gastric cancer, 58 with colorectal cancer, and 23 with thyroid
      cancer. The number of target lesions by RECIST 1.1 was significantly lower than
      that by RECIST 1.0 (P<0.001). Because of new lymph node criteria, fourteen
      patients (3.1%) had no target lesions when adopting RECIST 1.1. RECIST 1.1 showed
      high concordance with RECIST 1.0 in the assessment of tumor responses (k =
      0.903). Sixteen patients (4.8%) showed disagreement between the two criteria.
      CONCLUSION: This pooled study demonstrated that RECIST 1.1 showed a highly
      concordant response assessment with RECIST 1.0 in patients with metastatic
      cancer.

PMID- 25767611
TI  - Clinical implication of performance status in patients with hepatocellular
      carcinoma complicating with cirrhosis.
AB  - BACKGROUND AND AIMS: The aims of our study were to elucidate the relationship
      between baseline characteristics of hepatocellular carcinoma (HCC) patients
      complicating with liver cirrhosis (LC) and performance status (PS) and to
      investigate the impact of PS on survival in patients with HCC complicating with
      LC. METHODS: In a total of 1003 patients diagnosed with HCC complicating with LC,
      we divided into two groups of PS >=1 (n=251) and PS 0 (n=752) as evaluated by
      using the Eastern Cooperative Oncology Group criteria at the time of HCC
      diagnosis. Baseline characteristics between these two groups were compared. We
      also performed univariate and multivariate analyses of factors contributing to
      overall survival (OS). RESULTS: The median follow-up period was 1.6 years in the
      PS >=1 group and 3.1 years in the PS 0 group. The 1-, 3- and 5-year OS rates
      after each initial therapy for HCC were 90.3%, 67.4% and 49.8%, respectively, in
      the PS 0 group and 73.4%, 42.0% and 17.7%, respectively, in the PS >=1 group
      (P<0.001). A worse PS was significantly associated with age, gender, Child-Pugh
      classification, HCC stage, Japan Integrated Staging score, initial treatment
      option for HCC, maximum tumor size, alanine aminotransferase value,
      hypoalbuminemia, hyperbilirubinemia, renal insufficiency, hyponatremia,
      prothrombin time prolongation, platelet count and tumor marker level. In
      multivariate analyses, poorer PS was an independent predictor linked to OS with a
      hazard ratio of 1.773 (P<0.001). CONCLUSIONS: PS was closely associated with
      status of HCC patients with LC and could be an important predictor for these
      populations.

PMID- 25767612
TI  - CFD modeling and image analysis of exhaled aerosols due to a growing bronchial
      tumor: towards non-invasive diagnosis and treatment of respiratory obstructive
      diseases.
AB  - Diagnosis and prognosis of tumorigenesis are generally performed with CT, PET, or
      biopsy. Such methods are accurate, but have the limitations of high cost and
      posing additional health risks to patients. In this study, we introduce an
      alternative computer aided diagnostic tool that can locate malignant sites caused
      by tumorigenesis in a non-invasive and low-cost way. Our hypothesis is that
      exhaled aerosol distribution is unique to lung structure and is sensitive to
      airway structure variations. With appropriate approaches, it is possible to
      locate the disease site, determine the disease severity, and subsequently
      formulate a targeted drug delivery plan to treat the disease. This study
      numerically evaluated the feasibility of the proposed breath test in an image
      based lung model with varying pathological stages of a bronchial squamous tumor.
      Large eddy simulations and a Lagrangian tracking approach were used to model
      respiratory airflows and aerosol dynamics. Respirations of tracer aerosols of 1
      um at a flow rate of 20 L/min were simulated, with the distributions of exhaled
      aerosols recorded on a filter at the mouth exit. Aerosol patterns were quantified
      with multiple analytical techniques such as concentration disparity, spatial
      scanning and fractal analysis. We demonstrated that a growing bronchial tumor
      induced notable variations in both the airflow and exhaled aerosol distribution.
      These variations became more apparent with increasing tumor severity. The exhaled
      aerosols exhibited distinctive pattern parameters such as spatial probability,
      fractal dimension, and multifractal spectrum. Results of this study show that
      morphometric measures of the exhaled aerosol pattern can be used to detect and
      monitor the pathological states of respiratory diseases in the upper airway. The
      proposed breath test also has the potential to locate the site of the disease,
      which is critical in developing a personalized, site-specific drug delivery
      protocol. 

PMID- 25767613
TI  - An anion-induced hydrothermal oriented-explosive strategy for the synthesis of
      porous upconversion nanocrystals.
AB  - Rare-earth (RE)-doped upconversion nanocrystals (UCNCs) are deemed as the
      promising candidates of luminescent nanoprobe for biological imaging and
      labeling. A number of methods have been used for the fabrication of UCNCs, but
      their assembly into porous architectures with desired size, shape and
      crystallographic phase remains a long-term challenging task. Here we report a
      facile, anion-induced hydrothermal oriented-explosive method to simultaneously
      control size, shape and phase of porous UCNCs. Our results confirmed the anion
      induced hydrothermal oriented-explosion porous structure, size and phase
      transition for the cubic/hexagonal phase of NaLuF4 and NaGdF4 nanocrystals with
      various sizes and shapes. This general method is very important not only for
      successfully preparing lanthanide doped porous UCNCs, but also for clarifying the
      formation process of porous UCNCs in the hydrothermal system. The synthesized
      UCNCs were used for in vitro and in vivo CT imaging, and could be acted as the
      potential CT contrast agents. 

PMID- 25767614
TI  - Nano-enabled SERS reporting photosensitizers.
AB  - To impart effective cellular damage via photodynamic therapy (PDT), it is vital
      to deliver the appropriate light dose and photosensitizer concentration, and to
      monitor the PDT dose delivered at the site of interest. In vivo monitoring of
      photosensitizers has in large part relied on their fluorescence emission.
      Palladium-containing photosensitizers have shown promising clinical results by
      demonstrating near full conversion of light to PDT activity at the cost of having
      undetectable fluorescence. We demonstrate that, through the coupling of plasmonic
      nanoparticles with palladium-photosensitizers, surface-enhanced Raman scattering
      (SERS) provides both reporting and monitoring capability to otherwise quiescent
      molecules. Nano-enabled SERS reporting of photosensitizers allows for the
      decoupling of the therapeutic and imaging mechanisms so that both phenomena can
      be optimized independently. Most importantly, the design enables the use of the
      same laser wavelength to stimulate both the PDT and imaging features, opening the
      potential for real-time dosimetry of photosensitizer concentration and PDT dose
      delivery by SERS monitoring. 

PMID- 25767615
TI  - MRI visible drug eluting magnetic microspheres for transcatheter intra-arterial
      delivery to liver tumors.
AB  - Magnetic resonance imaging (MRI)-visible amonafide-eluting alginate microspheres
      were developed for targeted arterial-infusion chemotherapy. These alginate
      microspheres were synthesized using a highly efficient microfluidic gelation
      process. The microspheres included magnetic clusters formed by USPIO
      nanoparticles to permit MRI and a sustained drug-release profile. The
      biocompatibility, MR imaging properties and amonafide release kinetics of these
      microspheres were investigated during in vitro studies. A xenograft rodent model
      was used to demonstrate the feasibility to deliver these microspheres to liver
      tumors using hepatic transcatheter intra-arterial infusions and potential to
      visualize the intra-hepatic delivery of these microspheres to both liver tumor
      and normal tissues with MRI immediately after infusion. This approach offer the
      potential for catheter-directed drug delivery to liver tumors for reduced
      systemic toxicity and superior therapeutic outcomes. 

PMID- 25767616
TI  - Magnetoliposomes loaded with poly-unsaturated fatty acids as novel theranostic
      anti-inflammatory formulations.
AB  - We describe the preparation, physico-chemical characterization and anti
      inflammatory properties of liposomes containing the superparamagnetic
      nanoparticle Nanotex, the fluorescent dye Rhodamine-100 and omega-3
      polyunsaturated fatty acid ethyl ester (omega-3 PUFA-EE), as theranostic anti
      inflammatory agents. Liposomes were prepared after drying chloroform suspensions
      of egg phosphatidylcholine, hydration of the lipid film with aqueous phases
      containing or not Nanotex, Rhodamine-100 dye or omega-3 PUFA-EE, and eleven
      extrusion steps through nanometric membrane filters. This resulted in uniform
      preparations of liposomes of approximately 200 nm diameter. Extraliposomal
      contents were removed from the preparation by gel filtration chromatography. High
      Resolution Magic Angle Spinning (1)H NMR Spectroscopy of the liposomal
      preparations containing omega-3 PUFA-EE revealed well resolved (1)H resonances
      from highly mobile omega-3 PUFA-EE, suggesting the formation of very small (ca.
      10 nm) omega-3 PUFA-EE nanogoticules, tumbling fast in the NMR timescale.
      Chloroform extraction of the liposomal preparations revealed additionally the
      incorporation of omega-3 PUFA-EE within the membrane domain. Water diffusion
      weighted spectra, indicated that the goticules of omega-3 PUFA-EE or its
      insertion in the membrane did not affect the average translational diffusion
      coefficient of water, suggesting an intraliposomal localization, that was
      confirmed by ultrafiltration. The therapeutic efficacy of these preparations was
      tested in two different models of inflammatory disease as inflammatory colitis or
      the inflammatory component associated to glioma development. Results indicate
      that the magnetoliposomes loaded with omega-3 PUFA-EE allowed MRI visualization
      in vivo and improved the outcome of inflammatory disease in both animal models,
      decreasing significantly colonic inflammation and delaying, or even reversing,
      glioma development. Together, our results indicate that magnetoliposomes loaded
      with omega-3 PUFA-EE may become useful anti-inflammatory agents for image guided
      drug delivery. 

PMID- 25767617
TI  - Autoregulation of inducible nitric oxide synthase expression by RNA interference
      provides neuroprotection in neonatal rats.
AB  - We have shown that autoregulation of gene expression by RNA interference is
      achievable in cell cultures. To determine whether this novel concept could be
      used to produce neuroprotection under in vivo condition, postnatal day (PND) 3
      rats received intracerebroventricular injection of lentivirus that carried or did
      not carry code for short hairpin RNA (shRNA) of inducible nitric oxide synthase
      (iNOS). The expression of this shRNA was controlled by an iNOS promoter (piNOS
      shRNA) or cytomegalovirus promoter (pCMV-shRNA). The rats were subjected to brain
      hypoxia-ischemia at PND7. Ischemic brain tissues had increased iNOS expression.
      This increase was attenuated by virus carrying piNOS-shRNA. Virus carrying pCMV
      shRNA reduced iNOS to a level that was lower than control. Brain tissue loss and
      functional impairment after the hypoxia-ischemia were attenuated by the virus
      carrying piNOS-shRNA but not by pCMV-shRNA. Our results provide proof-of-concept
      evidence that autoregulation of iNOS expression by RNA interference induces
      neuroprotection in vivo and that appropriate regulation of gene expression is
      important. 

PMID- 25767618
TI  - Molecular magnetic resonance imaging of angiogenesis in vivo using polyvalent
      cyclic RGD-iron oxide microparticle conjugates.
AB  - Angiogenesis is an essential component of tumour growth and, consequently, an
      important target both therapeutically and diagnostically. The cell adhesion
      molecule alpha(v)beta(3) integrin is a specific marker of angiogenic vessels and
      the most prevalent vascular integrin that binds the amino acid sequence arginine
      glycine-aspartic acid (RGD). Previous studies using RGD-targeted nanoparticles
      (20-50 nm diameter) of iron oxide (NPIO) for magnetic resonance imaging (MRI) of
      tumour angiogenesis, have identified a number of limitations, including non
      specific extravasation, long blood half-life (reducing specific contrast) and low
      targeting valency. The aim of this study, therefore, was to determine whether
      conjugation of a cyclic RGD variant [c(RGDyK)], with enhanced affinity for
      alpha(v)beta(3), to microparticles of iron oxide (MPIO) would provide a more
      sensitive contrast agent for imaging of angiogenic tumour vessels. Cyclic RGD
      [c(RGDyK)] and RAD [c(RADyK)] based peptides were coupled to 2.8 MUm MPIO, and
      binding efficacy tested both in vitro and in vivo. Significantly greater specific
      binding of c(RGDyK)-MPIO to S-nitroso-n-acetylpenicillamine (SNAP)-stimulated
      human umbilical vein endothelial cells in vitro than PBS-treated cells was
      demonstrated under both static (14-fold increase; P < 0.001) and flow (44-fold
      increase; P < 0.001) conditions. Subsequently, mice bearing subcutaneous
      colorectal (MC38) or melanoma (B16F10) derived tumours underwent in vivo MRI pre-
      and post-intravenous administration of c(RGDyK)-MPIO or c(RADyK)-MPIO. A
      significantly greater volume of MPIO-induced hypointensities were found in
      c(RGDyK)-MPIO injected compared to c(RADyK)-MPIO injected mice, in both tumour
      models (P < 0.05). Similarly, administration of c(RGDyK)-MPIO induced a greater
      reduction in mean tumour T(2)* relaxation times than the control agent in both
      tumour models (melanoma P < 0.001; colorectal P < 0.0001). Correspondingly, MPIO
      density per tumour volume assessed immunohistochemically was significantly
      greater for c(RGDyK)-MPIO than c(RADyK)-MPIO injected animals, in both melanoma
      (P < 0.05) and colorectal (P < 0.0005) tumours. In both cases, binding of
      c(RGDyK)-MPIO co-localised with alpha(v)beta(3) expression. Comparison of RGD
      targeted and dynamic contrast enhanced (DCE) MRI assessment of tumour perfusion
      indicated sensitivity to different vascular features. This study demonstrates
      specific binding of c(RGDyK)-MPIO to alpha(v)beta(3) expressing neo-vessels, with
      marked and quantifiable contrast and rapid clearance of unbound particles from
      the blood circulation compared to NPIO. Combination of this molecular MRI
      approach with conventional DCE MRI will enable integrated molecular, anatomical
      and perfusion tumour imaging.

PMID- 25767620
TI  - Two independent epigenetic biomarkers predict survival in neuroblastoma.
AB  - BACKGROUND: Neuroblastoma (NB) is the most common extracranial pediatric solid
      tumor with a highly variable clinical course, ranging from spontaneous regression
      to life-threatening disease. Survival rates for high-risk NB patients remain
      disappointingly low despite multimodal treatment. Thus, there is an urgent
      clinical need for additional biomarkers to improve risk stratification, treatment
      management, and survival rates in children with aggressive NB. RESULTS: Using
      gene promoter methylation analysis in 48 neuroblastoma tumors with microarray
      technology, we found a strong association between survival and gene promoter
      hypermethylation (P = 0.036). Hypermethylation of 70 genes significantly
      differentiated high-risk survivor patients from those who died during follow-up
      time. Sixteen genes with relevant roles in cancer biology were further validated
      in an additional cohort of 83 neuroblastoma tumors by bisulfite pyrosequencing.
      High promoter methylation rates of these genes were found in patients with
      metastatic tumors (either stage metastatic (M) or metastatic special (MS)), 18
      months or older at first diagnosis, MYCN amplification, relapsed, and dead.
      Notably, the degree of methylation of retinoblastoma 1 (RB1) and teratocarcinoma
      derived growth factor 1 (TDGF1) predicts event-free and overall survival
      independently of the established risk factors. In addition, low RB1 mRNA
      expression levels associate with poor prognosis suggesting that promoter
      methylation could contribute to the transcriptional silencing of this gene in NB.
      CONCLUSIONS: We found a new epigenetic signature predictive for NB patients'
      outcome: the methylation status of RB1 and TDGF1 associate with poorer survival.
      This information is useful to assess prognosis and improve treatment selection.

PMID- 25767622
TI  - Message from the New Editor-in-Chief.

PMID- 25767621
TI  - Identification of subgroup-specific miRNA patterns by epigenetic profiling of
      sporadic and Lynch syndrome-associated colorectal and endometrial carcinoma.
AB  - BACKGROUND: Altered expression of microRNAs (miRNAs) commonly accompanies
      colorectal (CRC) and endometrial carcinoma (EC) development, but the underlying
      mechanisms and clinicopathological correlations remain to be clarified. We
      focused on epigenetic mechanisms and aimed to explore if DNA methylation patterns
      in tumors depend on DNA mismatch repair (MMR) status, sporadic vs. Lynch
      associated disease, and geographic origin (Finland vs. Australia). Treatment of
      cancer cell lines with demethylating agents revealed 109 significantly
      upregulated miRNAs. Seven met our stringent criteria for possible methylation
      sensitive miRNAs and were used to screen patient specimens (205 CRCs and 36 ECs)
      by methylation-specific multiplex ligation-dependent probe amplification.
      RESULTS: Three miRNAs (129-2, 345, and 132) with low methylation levels in normal
      tissue and frequent hypermethylation in tumors were of particular interest.
      Hypermethylation of miR-345 and miR-132 associated with MMR deficiency in CRC
      regardless of geographic origin, and hypermethylation of miR-132 distinguished
      sporadic MMR-deficient CRC from Lynch-CRC. Finally, hypermethylation of miRNAs
      stratified 49 endometrial hyperplasias into low-methylator (simple hyperplasia)
      and high-methylator groups (complex hyperplasia with or without atypia) and
      suggested that miR-129-2 methylation in particular could serve as a marker of
      progression in early endometrial tumorigenesis. CONCLUSIONS: Our study identifies
      miR-345 and miR-132 as novel differentially methylated miRNAs in CRC, thereby
      facilitating sub-classification of CRC and links miR-129-2 methylation to early
      endometrial tumorigenesis.

PMID- 25767619
TI  - Theranostic impact of NG2/CSPG4 proteoglycan in cancer.
AB  - NG2/CSPG4 is an unusual cell-membrane integral proteoglycan widely recognized to
      be a prognostic factor, a valuable tool for ex vivo and non-invasive molecular
      diagnostics and, by virtue of its tight association with malignancy, a
      tantalizing therapeutic target in several tumour types. Although the biology
      behind its involvement in cancer progression needs to be better understood,
      implementation of NG2/CSPG4 in the routine clinical practice is attainable and
      has the potential to contribute to an improved individualized management of
      cancer patients. In this context, its polymorphic nature seems to be particularly
      valuable in the effort to standardize informative diagnostic procedures and
      consolidate forcible immunotherapeutic treatment strategies. We discuss here the
      underpinnings for this potential and highlight the benefits of taking advantage
      of the intra-tumour and inter-patient variability in the regulation of NG2/CSPG4
      expression. We envision that NG2/CSPG4 may effectively be exploited in
      therapeutic interventions aimed at averting resistance to target therapy agents
      and at interfering with secondary lesion formation and/or tumour recurrence. 

PMID- 25767623
TI  - Metastatic Neuroendocrine Tumour in a Renal Transplant Recipient: Dual-Tracer PET
      CT with (18)F-FDG and (68)Ga-DOTANOC in This Rare Setting.
AB  - Recipients of renal transplant are at increased risk of developing various
      malignancies, especially post-transplant lymphoproliferative disorder (PTLD) and
      skin cancers. Neuroendocrine tumours (NET) of the gastrointestinal tract have not
      been reported in this setting. Here we describe the case of a 75-year-old male
      who had undergone renal transplant 8 years back and now presented with
      significant weight loss and backache, clinically suspected as PTLD. (18)F
      Fluordeoxyglucose ((18)F-FDG) positron emission tomography-computed tomography
      (PET-CT) showed hypermetabolic lesions in the liver and rectum, raising the
      suspicion of PTLD. However, biopsy from the liver lesion showed poorly
      differentiated NET. (68)Ga-labelled [1,4,7,10-tetraazacyclododecane-1,4,7,10
      tetraacetic acid]-1-NaI(3)-octreotide ((68)Ga-DOTANOC) PET-CT was then done,
      which confirmed the primary lesion in the rectum with liver metastases. 

PMID- 25767624
TI  - Usefulness of Additional SPECT/CT Identifying Lymphatico-renal Shunt in a Patient
      with Chyluria.
AB  - Lymphoscintigraphy is known to be a useful and non-invasive modality for the
      evaluation of lymphatic abnormality. However, lymphoscintigraphy has limitations
      in evaluating chyluria because of its lack of anatomical information. Additional
      single-photon emission computed tomography (SPECT) combined with computed
      tomography (CT) was considered to be potentially helpful in detecting the
      abnormal lymphatico-renal communication. A 20-year-old male patient was referred
      to our hospital for evaluation of recurrent chyluria. During the third recurrence
      of chyluria, additional SPECT/CT along with lymphoscintigraphy was performed for
      evaluation. From the combined SPECT/CT images, lymphatic drainage of radiotracers
      to the kidney was well visualized, helping diagnosis of a patient with chyluria. 

PMID- 25767625
TI  - Unexpected Second Primary Malignancies Detected by F-18 FDG PET/CT During Follow
      up for Primary Malignancy: Two Case Reports.
AB  - As the survival rate of cancer patients has increased over the last few decades,
      the risk of cancer survivors developing second primary malignancies has gained
      attention. We report two rare cases of second primary hematologic malignancy
      detected by (18)F-fluorodeoxyglucose (F-18 FDG) positron emission
      tomography/computed tomography (PET/CT) during follow-up for primary solid
      malignancies. Acute lymphoblastic leukemia developed in a breast cancer patient
      and non-Hodgkin lymphoma in an anal cancer patient. F-18 FDG PET/CT findings led
      to the diagnosis of unexpected second primary hematologic malignancy in cancer
      survivors in these two cases. 

PMID- 25767626
TI  - Retroperitoneal Bronchogenic Cyst Presenting Paraadrenal Tumor Incidentally
      Detected by (18)F-FDG PET/CT.
AB  - A follow-up (18)F-fluorodeoxyglucose ((18)F-FDG) PET/CT scan of a 57-year-old
      asymptomatic male who had undergone total thyroidectomy for thyroid cancer
      revealed a 5.0 * 4.0-cm, well-defined, ovoid-shaped mass around the left adrenal
      gland without definite FDG uptake. On the adrenal CT scan, the left paraadrenal
      tumor showed high attenuation on the precontrast scan without enhancement. The
      average Hounsfield unit (HU) was 58.1 on the precontrast scan and 58.4 on the
      postcontrast scan. The patient underwent laparoscopic adrenalectomy for resection
      of the left paraadrenal tumor. The final histopathologic examination revealed a
      bronchogenic cyst. Although retroperitoneal bronchogenic cysts are rare, they
      should be considered in the differential diagnosis of retroperitoneal cystic
      tumors. The preoperative diagnosis is difficult, but a contrast-enhanced CT scan
      or (18)F-FDG PET/CT scan may be useful for differentiating hyperattenuated cysts
      from other soft tissue masses. 

PMID- 25767627
TI  - Unusual Adrenal Gland Metastasis in a Patient with Follicular Carcinoma of the
      Thyroid Evidenced by (18)F-FDG PET/CT and Confirmed by Biopsy.

PMID- 25767628
TI  - (18)F-FDG PET/CT for Detection of Metachronous Hodgkin's Disease in Patients with
      Myelofibrosis.

PMID- 25767629
TI  - Cardiac amyloidosis detected on tc-99m bone scan.

PMID- 25767630
TI  - RETRACTED ARTICLE: A Case Series of Four Patients With Clinically Significant
      Radiomicrosphere Pneumonitis After Yttrium-90 Radioembolization from the
      Perspective of Lung Dosimetry.

PMID- 25767631
TI  - Evidence for an association between tako-tsubo cardiomyopathy and bronchial
      asthma: retrospective analysis in a primary care hospital.
AB  - OBJECTIVE: We investigated the prevalence of bronchial asthma in patients with
      Tako-Tsubo Syndrome (TTS). DESIGN: This retrospective case-series study was
      conducted in a primary care hospital in Zurich, Switzerland. Data of all patients
      with newly diagnosed TTS (2002 - 2012) were assessed electronically by the use of
      ICD-10. Asthma prevalence was compared to published epidemiologic data. SETTING:
      Bronchial asthma is characterized by airway inflammation and, during attack,
      release of endogenous catecholamines. Sympathomimetic drugs are the mainstay of
      treatment for asthma patients. Likewise, catecholamine mediated diffuse
      microvascular myocardial dysfunction seems to be of critical importance for the
      development of TTS. RESULTS: 20 cases of TTS were identified. 90% were female,
      showed a median age of 70+/-13y [25y - 90y], an apical and/or midventricular
      ballooning pattern with preserved basal function and a median initial LVEF of
      34+/-9% [25% - 55%]. 65% of patients underwent coronary angiography to rule out
      significant coronary artery disease. Hypertension was present in 45% of patients,
      35% were smokers, none was suffering from diabetes. Prevalence of asthma in
      patients with TTS was significantly higher compared to the normal population (25%
      vs. 7%, p=0.012). In 30% of the TTS patients an iatrogenic cause for development
      of TTS was identified. CONCLUSION: Prevalence of asthma was significantly higher
      in patients with TTS compared to epidemiologic data from an age-matched
      population. Phenotypes of patients developing obstructive ventilatory disease and
      TTS might share common pathogenic mechanisms beyond the use of bronchodilatators.
      In addition, we identified other iatrogenic etiologies in patients with TTS.

PMID- 25767633
TI  - LETTER TO THE EDITOR Performance of the ViroSeq(r) HIV-1 Genotyping System v2.0
      in Central Africa.
AB  - Resistance genotypes in pol gene of HIV-1 were obtained by the ViroSeq((r)) HIV-1
      Genotyping System v2.0 (Celera Diagnostics, Alameda, CA, USA) in 138 of 145 (95%)
      antiretroviral treatment-experienced adults in virological failure living in
      Central Africa (Cameroon, Central African Republic, Chad, Gabon). HIV-1 group M
      exhibited broad genetic diversity. Performance of the 7 ViroSeq((r)) sequencing
      primers showed high failure rate, from 3% to 76% (D: 76%; F: 17%; A and H: 15%; G
      and B: 4%; C: 3%). These findings emphasize the need of updating the ViroSeq((r))
      HIV-1 genotyping system for non-B subtypes HIV-1. 

PMID- 25767632
TI  - Theory of Inpatient Circadian Care (TICC): A Proposal for a Middle-Range Theory.
AB  - The circadian system controls the daily rhythms of a variety of physiological
      processes. Most organisms show physiological, metabolic and behavioral rhythms
      that are coupled to environmental signals. In humans, the main synchronizer is
      the light/dark cycle, although non-photic cues such as food availability, noise,
      and work schedules are also involved. In a continuously operating hospital, the
      lack of rhythmicity in these elements can alter the patient's biological rhythms
      and resilience. This paper presents a Theory of Inpatient Circadian Care (TICC)
      grounded in circadian principles. We conducted a literature search on biological
      rhythms, chronobiology, nursing care, and middle-range theories in the databases
      PubMed, SciELO Public Health, and Google Scholar. The search was performed
      considering a period of 6 decades from 1950 to 2013. Information was analyzed to
      look for links between chronobiology concepts and characteristics of inpatient
      care. TICC aims to integrate multidisciplinary knowledge of biomedical sciences
      and apply it to clinical practice in a formal way. The conceptual points of this
      theory are supported by abundant literature related to disease and altered
      biological rhythms. Our theory will be able to enrich current and future
      professional practice. 

PMID- 25767634
TI  - Comparison of Rates of Death Having any Death-Certificate Mention of Heart,
      Kidney, or Liver Disease Among Persons Diagnosed with HIV Infection with those in
      the General US Population, 2009-2011.
AB  - OBJECTIVE: Compare age-adjusted rates of death due to liver, kidney, and heart
      diseases during 2009-2011 among US residents diagnosed with HIV infection with
      those in the general population. METHODS: Numerators were numbers of records of
      multiple-cause mortality data from the national vital statistics system with an
      ICD-10 code for the disease of interest (any mention, not necessarily the
      underlying cause), divided into those 1) with and 2) without an additional code
      for HIV infection. Denominators were 1) estimates of persons living with
      diagnosed HIV infection from national HIV surveillance system data and 2) general
      population estimates from the US Census Bureau. We compared age-adjusted rates
      overall (unstratified by sex, race/ethnicity, or region of residence) and
      stratified by demographic group. RESULTS: Overall, compared with the general
      population, persons diagnosed with HIV infection had higher age-adjusted rates of
      death reported with hepatitis B (rate ratio [RR]=42.6; 95% CI: 34.7-50.7),
      hepatitis C (RR=19.4; 95% CI: 18.1-20.8), liver disease excluding hepatitis B or
      C (RR=2.1; 95% CI: 1.8-2.3), kidney disease (RR=2.4; 95% CI: 2.2-2.6), and
      cardiomyopathy (RR=1.9; 95% CI: 1.6-2.3), but lower rates of death reported with
      ischemic heart disease (RR=0.6; 95% CI: 0.6-0.7) and heart failure (RR=0.8; 95%
      CI: 0.6-0.9). However, the differences in rates of death reported with the heart
      diseases were insignificant in some demographic groups. CONCLUSION: Persons with
      HIV infection have a higher risk of death with liver and kidney diseases reported
      as causes than the general population.

PMID- 25767635
TI  - Surgery and diagnostic imaging in abdominal Crohn's disease.
AB  - Surgery is well-established option for the treatment of Crohn's disease that is
      refractory to medical therapy and for complications of the disease, including
      strictures, fistulas, abscesses, bleeding that cannot be controlled
      endoscopically, and neoplastic degeneration. For a condition like Crohn's
      disease, where medical management is the rule, other indications for surgery are
      considered controversial, because the therapeutic effects of surgery are limited
      to the resolution of complications and the rate of recurrence is high, especially
      at sites of the surgical anastomosis. In the authors' opinion, however, surgery
      should not be considered a last-resort treatment: in a variety of situations, it
      should be regarded as an appropriate solution for managing this disease. Based on
      a review of the literature and their own experience, the authors examine some of
      the possibilities for surgical interventions in Crohn's disease and the roles
      played in these cases by diagnostic imaging modalities. 

PMID- 25767637
TI  - Ultrasound findings in the omental bursa: a short pictorial essay.
AB  - The omental bursa is a complex and important anatomical region. It serves as a
      barrier to block pathological processes, but it is also a channel for disease
      spread in the abdominal cavity. It is a large recess of the peritoneal cavity
      formed by a double-layered fold of serous peritoneum situated inferiorly to the
      liver, posteriorly to the lesser omentum and the stomach and anteriorly to the
      pancreas. Ultrasound (US) has an important role in the study of the omental
      bursa, as it is generally the first examination to be performed in the presence
      of abdominal pain. US is inexpensive, widely available and able to identify many
      of the alterations that may occur in the abdomen. However, US findings are often
      varied and unspecific, ranging from fluid collections to diffuse infiltration.
      Familiarity with the various diseases that may affect the omental bursa is
      essential in order to be able to identify them during US examination of the
      abdomen. US imaging is useful in the follow-up after treatment and to guide
      drainage of fluid collections. 

PMID- 25767636
TI  - Imaging techniques and combined medical and surgical treatment of perianal
      Crohn's disease.
AB  - Crohn's disease is a chronic inflammatory disease which may involve any segment
      of the gastrointestinal tract, most frequently the terminal ileum, the large
      intestine, and the perianal region. The symptoms of perianal Crohn's disease
      include skin disorders, hemorrhoids, anal ulcers, anorectal stenosis, perianal
      abscesses and fistulas, rectovaginal fistulas and carcinoma of the perianal
      region. The perianal manifestations of Crohn's disease cause great discomfort to
      the patient and are among the most difficult aspects to treat. Management of
      perianal disease requires a combination of different imaging modalities and a
      close cooperation between gastroenterologists and dedicated surgeons. 

PMID- 25767638
TI  - Post-treatment sequential ultrasound imaging of follicular cyst in a crossbred
      dairy cow.
AB  - Several studies in dairy cattle have investigated the final outcome of different
      treatment regimens in follicular cyst condition. However, sequential monitoring
      of the response of follicular cysts to these treatments is rather scanty. In this
      paper, we present the response of a large follicular cyst in a pluriparous
      crossbred dairy cow with prolonged conception failure to human chorionic
      gonadotropin, hCG (3,000 IU; day 0) and cloprostenol (500 MUg; day 9) treatment.
      Using transrectal ultrasonography (USG), reproductive tract was imaged daily
      beginning day 0 until day 11. The follicular cyst showed a consistent regression
      to a very small anechoic area on day 7 and was undetectable thereafter.
      Concurrently, there was development of a new dominant follicle that was first
      detected on day 4 and showed progressive growth to preovulatory stage. The cow
      was inseminated and ovulation occurred, as diagnosed by the presence of a corpus
      luteum (CL) 7 days later, but conception did not occur. The animal was re
      inseminated after estrus detection in the estrous cycle that immediately
      followed. Pregnancy diagnosis was performed on 30 and 60 days post-insemination
      (DPI) and the cow was confirmed to be pregnant. This paper underscores the
      importance of diagnostic ultrasound in veterinary medicine, especially in the
      management of reproductive problems. 

PMID- 25767639
TI  - Ultrasonographic findings in Crohn's disease.
AB  - In recent years transabdominal bowel sonography has become a first-line modality
      both in the diagnosis and in the follow-up of inflammatory bowel diseases,
      especially Crohn's disease, reaching values of sensitivity ranging from 84 to 93
      %. In particular, its role is very useful in the early diagnosis of complications
      such as stenosis, phlegmons, abscesses and fistulae. According to the available
      literature the ability of US to provide information about disease activity is
      still under debate and further studies are necessary. In this regard, of
      fundamental importance is the use of additional techniques such as color- and
      power-Doppler and contrast-enhanced ultrasound. The purpose of this paper is to
      report the main sonographic intestinal and extraintestinal findings detectable in
      Crohn's disease. 

PMID- 25767640
TI  - Power Doppler sonography to predict the risk of surgical recurrence of Crohn's
      disease.
AB  - PURPOSE: The aim of this work is to investigate the role of power Doppler
      sonography as an additional predictor of surgical recurrence in Crohn's disease.
      METHODS: A sample of 33 patients, with ileal or ileocolonic Crohn's disease, that
      had underwent intestinal resection, were retrospectively enrolled. All patients
      had bowel ultrasonography 7-16 months after resection. Power Doppler sonography
      of the preanastomotic ileum was evaluated as a possible prognostication tool to
      assess the risk of long-term need for reoperation. RESULTS: The absolute
      incidence of surgical recurrence in those who had a positive power Doppler was 42
      %, while that of those who had a negative power Doppler was 28.6 %. Combining the
      power Doppler with bowel wall thickness, the surgical recurrence risk grew from
      41.2 % of those with a positive power Doppler and thickness >3 mm to 55.6 % of
      those with a positive power Doppler and thickness >6 mm. CONCLUSIONS: Power
      Doppler look to be another useful prediction tool for the personalization of
      patient's care. It could be useful to perform power Doppler in all patients with
      a wall thickness >5 mm: for those who have a positive power Doppler it may be
      indicated as a more aggressive prophylactic therapy.

PMID- 25767642
TI  - Premenstrual inguinal swelling and pain caused by endometriosis in the Bartholin
      gland: a case report.
AB  - Endometriosis is a pathological condition characterized by the presence of
      endometrial tissue outside the endometrium. The authors describe a case of
      endometriosis in the Bartholin gland, which was initially diagnosed as a
      Bartholin gland cyst. The correct diagnosis was later made on the basis of the
      patient history and the results of the ultrasound examination. Endometriosis in
      the Bartholin gland should be considered in the presence of dyspareunia, cyclic
      swelling and pain at the vulvar level, and characteristic ultrasound findings. 

PMID- 25767641
TI  - Diagnostic accuracy of emergency physician performed graded compression
      ultrasound study in acute appendicitis: a prospective study.
AB  - PURPOSE: Accurate early diagnosis of appendicitis can decrease its complications
      and minimize the mortality, morbidity and costs. This prospective study evaluates
      the accuracy of bedside emergency physician performed ultrasound study diagnosis
      in acute appendicitis. METHODS: Patients who were suspicious to have appendicitis
      based on their clinical findings were included and underwent emergency physician
      performed ultrasound study. Then they were followed up until the recognition of
      final diagnosis based on pathology report or identification of an alternative
      diagnosis. Ultrasound studies were done by post-graduate year three emergency
      medicine residents or emergency medicine attending physicians who were attended
      in a 4 h didactic and practical course and with 7.5 MHz linear probe both in
      longitudinal and axial axes. RESULTS: Ninety-seven patients were included and
      analyzed. 27 (27.8 %) of patients had appendicitis according to the results of
      emergency physicians performed ultrasound studies. 19 (70.37 %) of them had
      appendicitis according to their pathologic reports too. Forty-three (44.3 %) of
      patients had appendicitis according to pathology reports. Only 19 (44.18 %) of
      them were diagnosed by emergency physicians. Emergency physician performed
      ultrasound study had a sensitivity of 44.18 %, specificity of 85.18 %, positive
      predictive value of 70.37 %, negative predictive value of 65.71 % and overall
      accuracy of 67.01 % in diagnosing appendicitis in patients clinically suspicious
      to have acute appendicitis. CONCLUSION: Emergency physician performed bedside
      ultrasound has an acceptable overall accuracy but its sensitivity is low thus it
      can help emergency physicians to diagnose the acute appendicitis when used in
      conjunction with other clinical and para-clinical evaluations but not per se.

PMID- 25767643
TI  - Acquired unilateral pulmonary vein atresia in a 3-year-old boy.
AB  - While unilateral pulmonary venous atresia (UPVA) most commonly presents as an
      extremely rare late embryological defect resulting in complete occlusion or
      absence of the PV pathway, it may also be an acquired pathology. We present a 3
      year-old boy who presented with mild respiratory distress. Neonatal
      echocardiographic investigations revealed normal mediastinal anatomy and
      pulmonary vasculature with a bicuspid aortic valve. However, follow-up Doppler
      investigation revealed a pulmonary artery size difference with minimal forward
      flow and reverse flow during diastole. Absence of the left pulmonary veins and
      the presence of collaterals draining to the innominate vein confirmed the
      diagnosis of acquired UPVA. Our case represents the first case of acquired UPVA
      in conjunction with a normally functioning bicuspid aortic valve. The Doppler
      flow patterns discussed might be of significant interest to pediatricians,
      cardiologists and imaging specialists. These findings suggest that acquired UPVA
      should be considered in the differential diagnosis of such patients when
      radiographic and echocardiographic findings may rule out other more common
      diagnoses. While the management of such a condition remains unclear and
      conservative management was agreed upon for our patient, the vulnerability of
      such cases warrants timely diagnosis and routine monitoring. 

PMID- 25767644
TI  - Sonographic findings of extensor digiti minimi triggering caused by thickened
      extensor retinaculum.
AB  - Trigger finger is a common well recognized condition and involves the flexor
      tendons at the A1 pulley in the palm. Triggering of the extensor tendons is a
      very rare clinical entity. We report a rare case of extensor triggering of little
      finger caused by constriction of the extensor digiti minimi by a markedly
      thickened extensor retinaculum (ER) at the wrist, well delineated dynamically by
      real-time high-resolution ultrasound. The patient underwent release of thickened
      ER and was asymptomatic immediately. 

PMID- 25767645
TI  - In-continuity neuroma of the median nerve after surgical release for carpal
      tunnel syndrome: case report.
AB  - Iatrogenic injuries of the median nerve after surgical release for carpal tunnel
      syndrome resulting in the formation of a neuroma are rare. We present here the
      case of two patients, one with a bifid median nerve, showing in-continuity
      neuroma after surgical release for carpal tunnel syndrome. The patients reported
      persistent post-operative pain and showing symptoms. In both cases, ultrasound
      showed an in-continuity neuroma with a hypoechoic and enlarged median nerve at
      the carpal tunnel. The case report shows that ultrasound may be helpful in
      confirming the clinical diagnosis of neuroma and it is useful for evaluation of
      the percentage of the area affected by the tear. 

PMID- 25767646
TI  - Diagnosis and management of Crohn's disease.

PMID- 25767647
TI  - Morel-Lavallee lesion of the knee in a soccer player.

PMID- 25767648
TI  - The Use of the Internet to Meet Sexual Partners: A Comparison of Non
      Heterosexually-Identified Men with Heterosexually-Identified Men and Women.
AB  - In 2008, we conducted online interviews with 65 self-identified adult
      heterosexual men and women and gay/bisexual men to explore perceptions and
      experiences with meeting people online. Reasons for meeting people online,
      desired partner characteristics, and the process of connecting for sex paralleled
      those observed in real-life; but the Internet allowed people to identify more
      partners and specific partner characteristics. "Background checks" of online
      partners, even though often believed to be false, increased familiarity and trust
      leading to reduced perceived need for condom use. Participants said online condom
      use negotiation was easier, but usually occurred in face-to-face contexts in
      practice. (99).

PMID- 25767649
TI  - [Apnea during foreseeable difficult intubation for a large laryngeal cyst].

PMID- 25767650
TI  - Castle man disease: a case report and review of the literature.
AB  - The Castleman disease (CD) is a rare disease of unknown etiology, characterized
      histologically by angiofollicular lymphoid hyperplasia. It comes in two forms,
      unicentric and multicentric. We report a case of Castleman disease in a 58 year
      old man, who had consulted for chronic cervical lymphadenopathy. This case was a
      multicenteric and rapidly fatal despite aggressive treatment with
      corticosteroids, and chemotherapy. 

PMID- 25767651
TI  - [Multi-compartmentalized retroperitoneal cystic mass: hydatid cyst or nerve
      tumor?].

PMID- 25767652
TI  - [Pneumopericardium complicating thoracoabdominal trauma by hoof kick].

PMID- 25767653
TI  - [Neonatal infections: what is the place of obstetric history in the prevention of
      risk?].

PMID- 25767654
TI  - [Full term heterotopic pregnancy: report of a case].

PMID- 25767655
TI  - Hyperparathyroidism related to an ectopic parathyroid adenoma.

PMID- 25767656
TI  - Barriers to pilot mobile teleophthalmology in a rural hospital in Southern
      Malawi.
AB  - INTRODUCTION: Malawi has one of the highest HIV prevalences in Sub-Saharan
      Africa. The rate of eligible HIV-infected people being initiated on
      antiretroviral therapy (ART) and retained in HIV-care is currently far from
      adequate. Consequently, many people continue present with advanced
      immunosuppression at public health facilities, often with undiagnosed
      opportunistic infections (OIs). METHODS: In this context, mHealth was the
      innovation chosen to assist Eye Clinical Officers in early diagnosis of HIV
      related diseases having eye manifestations in a rural hospital in Thyolo,
      Southern Malawi. RESULTS: The mTeleophthalmology program began in October 2013,
      but was stopped prematurely due to organizational and technological barriers that
      compromised its feasibility. CONCLUSION: Sharing these barriers might be useful
      to inform the design of similar innovations in other resource-limited settings
      with a high HIV prevalence and a dearth of eye specialists with capacity to
      diagnose HIV-related retinopathies.

PMID- 25767658
TI  - [Angiomyolipoma of the kidney: about eight cases].

PMID- 25767657
TI  - Thyroid autoimmunity and function among Ugandan children and adolescents with
      type-1 diabetes mellitus.
AB  - INTRODUCTION: Up to 30% of type-1 diabetes mellitus (T1DM) patients have co
      existent thyroid autoimmunity with up to 50% of them having associated thyroid
      dysfunction. Routine screening for thyroid autoimmunity and dysfunction is
      recommended in all T1DM patients. However, this was not currently practiced in
      Ugandan paediatric diabetes clinics. There was also paucity of data regarding
      thyroid autoimmunity and dysfunction in African children and adolescents with
      diabetes mellitus. The objective of this study was to quantify the magnitude of
      thyroid autoimmunity and dysfunction in Ugandan children with TIDM. METHODS: This
      was a cross sectional descriptive study to determine the prevalence of thyroid
      autoantibodies and describe thyroid function among children and adolescents aged
      1-19 years with diabetes mellitus attending the paediatric diabetes clinic at
      Mulago National Referral Hospital, Kampala, Uganda. Following enrollment, we
      obtained details of clinical history and performed physical examination. Blood
      (plasma) was assayed to determine levels of antibodies to thyroid peroxidase
      (antiTPO), free thyroxine (FT4) and thyrotropin (TSH). RESULTS: The prevalence of
      thyroid autoimmunity was 7.3% (5/69). All antiTPO positive subjects were post
      pubertal, aged between 13-17 years with females comprising 3/5 of the antiTPO
      positive subjects. All study subjects were clinically euthyroid; however, 7.3%
      (5/69) of the study subjects had subclinical hypothyroidism. CONCLUSION: These
      data strengthen the argument for routine screening of all diabetic children and
      adolescents for thyroid autoimmunity (particularly anti-TPO) as recommended by
      international guidelines. We also recommend evaluation of thyroid function in
      diabetic children and adolescents to minimize the risk of undiagnosed thyroid
      dysfunction.

PMID- 25767659
TI  - [Diffuse brain atrophy in a Goldenhar syndrome: report of a case].

PMID- 25767660
TI  - [Decrease in HDL-cholesterol indicator of oxidative stress in type 2 diabetes].

PMID- 25767661
TI  - [Atypical praevia obstacle: about a case].

PMID- 25767662
TI  - Giant basal cell carcinoma of the scalp.

PMID- 25767663
TI  - [A baby like no other].

PMID- 25767664
TI  - [Vegetating idiopathic pyoderma gangrenosum].

PMID- 25767665
TI  - [Unusual presentations of Plummer-Vinson syndrome in Black African: report of two
      cases].

PMID- 25767666
TI  - Vestibular disorders in elderly patients: characteristics, causes and
      consequences.
AB  - INTRODUCTION: This study assessed vestibular disorders in elderly patients,
      describing the causes, clinical characteristics, therapies and treatment
      outcomes. METHODS: Five-year hospital-based prospective study, conducted at the
      ENT clinic of a tertiary referral center. Subjects were consecutive elderly
      patients with dizziness, treated and followed-up for a minimum of six months.
      Data was generated using structured questionnaire and case record files. Analyzed
      results were presented in simple descriptive forms as graphs and tables. RESULTS:
      Among the elderly patients, prevalence of vestibular disorders was 18.6%, 49.1%
      were retired, 71.9% were married, M:F was 1:1.1. Mean age+/-SD were 69.4+/-1.1
      and 69.0+/-0.8 years for males and females respectively. 56.9% of the patients
      presented early on experiencing the vestibular symptoms. The symptoms were
      associated with nausea or vomiting in 26.3%, with an aura in 12.3%. While 50.9%
      of the patients experienced intermittent symptoms, laterality of the symptoms was
      not clear in 45.6%. Positional vertigo was diagnosed in 33.3% while in 17.5%, the
      symptoms could be attributable to previous trauma or assaults. 31.6% of the
      elderly were referred to ENT surgeons by other specialties, 45.6% were managed
      with multidisciplinary approach, while 82.5% had the vestibular symptoms
      initially controlled with labyrinthine sedatives. At follow-up, 43.9% had
      intermittent periods of recurrence of symptoms. CONCLUSION: Prevalence of
      vestibular disorders in elderly patients is high, most patients present early
      with intermittent, relatively innocuous symptoms which may be difficult to
      lateralize. Positional vertigo was the most common cause, it is frequently
      relieved with labyrinthine sedatives but tends to recur intermittently.

PMID- 25767667
TI  - Clear cell sarcoma of tendons and aponeuroses of the parapharyngeal space: an
      unusual localization of a rare tumor (a case report and review of the
      literature).
AB  - The clear cell sarcoma of tendons and aponeuroses (CCSTA) is a rare soft tissue
      sarcoma in the head and neck region and parapharyngeal space. Over 95% of CCSTAs
      present in the extremities, with the head and neck region (1.9%) being an unusual
      site. This study presents an additional case of CCSTA of the head and neck region
      involving the parapharyngeal space in a 48-year-old men and review of the
      literature on CCSTA. 

PMID- 25767668
TI  - Prevalence of stress in Casablanca medical students: a cross-sectional study.
AB  - INTRODUCTION: Recently, an important literature data has reported that medical
      students experience stress more than students in other disciplines. In contrast,
      there is a significant shortage of the stress impact on the academic performance.
      The primary purpose of our study was to determine the prevalence of stress among
      Casablanca Medical students and to investigate if there is an association between
      stress and academic skills. METHODS: A total of 275 participants studying at
      Casablanca Medical School were included. The study was conducted using a self
      administered, anonymous questionnaire, which included four subscales on academic
      skills perception (Academic competence, Test competence, Time management and
      Strategic study habits) and a Test Anxiety scale to assess the degree of stress
      related to exams among medical students. RESULTS: The overall findings showed
      that 52.7% of respondents were stressed by examinations, and the highest stress
      prevalence was among the fifth-year medical students. Measures of comparative
      stress degrees between male and female students did not show any statistical
      significant differences (p=0.34). Correlation analysis revealed negative
      association between stress and academic competence (-0.394), test competence (
      0.426), time management (-0.240), strategic study (-0.183) respectively
      (p<0.001). CONCLUSION: Medical educators and psychologists have to increase
      clinical awareness of stress among medical students, by establishing strategies
      for stress management.

PMID- 25767669
TI  - [Congenital ptosis: experience of a tertiary Moroccan center and latest
      development].

PMID- 25767670
TI  - [Aorto-mesenteric compression syndrome in children: report of a case].

PMID- 25767671
TI  - Carcinoid tumor revealing pernicious anemia.

PMID- 25767672
TI  - Barriers to successful implementation of prevention-of-mother-to-child
      transmission (PMTCT) of HIV programmes in Malawi and Nigeria: a critical
      literature review study.
AB  - Mother-to-child-transmission (MTCT) of HIV still remains a significant route of
      new HIV infection in children in Malawi and Nigeria, despite the introduction of
      Prevention-of-Mother-to-Child-Transmission (PMTCT) of HIV programmes in both
      countries. A critical literature review, based on the findings from 12 primary
      research articles, explores the reasons for the inadequacy and failure of PMTCT.
      Findings show socioeconomic and sociocultural factors as the biggest barriers to
      the success of PMTCT programmes. Other factors include: limited male involvement,
      the organization of PMTCT and health workers' inefficiency. In conclusion, PMTCT
      programmes will remain inefficient unless these factors are addressed. There is
      an urgent need to strengthen PMTCT programmes by stakeholders through a
      collaborative strategic effort to ensure high PMTCT programme uptake in Malawi
      and Nigeria, in order to eliminate HIV/AIDS in children. 

PMID- 25767673
TI  - Assessing causes of death in the Cardiology Department of Yalgado Ouedraogo
      University Hospital.
AB  - INTRODUCTION: Analysis of the underlying causes of death can develop action plans
      for prevention of death that could be avoided. The aim of our study was to
      analyse the causes of cardiovascular deaths in the cardiology department of
      Yalgado Ouedraogo University Hospital. METHODS: The study was a descriptive
      retrospective study over a 24 month period among patients who died in the
      department. RESULTS: Prevalence of death in the cardiology department was of
      13.2%. Sex ratio was of 1.2 and 72.7% of patients were residing in Ouagadougou.
      Mean age of patients was 56.1 years and 59.4% of patients were under 65 years
      old. Hypertension was the major cardiovascular risk factor (46.1%) and 27.4% of
      patients had a medical history of dilated cardiomyopathy. Cardiogenic shock was
      the immediate cause of death in 55.5% of cases and the initial cause of death was
      hypertension and its complications in 46.1% of cases. Death was not notified in
      18% of cases and no death had been medically certified. CONCLUSION: Death
      statistics are the most reliable data for public health interventions. However,
      it is necessary to establish an effective method of data gathering according to
      the WHO standards in order to facilitate international comparison.

PMID- 25767674
TI  - Maxillofacial metastasis from breast cancer.
AB  - Metastatic tumors to paranasal sinuses are exclusively rare. In this paper, we
      report a case of breast carcinoma metastasizing to the right maxilla. The
      metastasis occurred 5 years after radical mastectomy and presented as a primary
      sinonasal mass. The diagnosis was confirmed with histopathologic and
      immunohistochemical examination however the patient died before starting any
      specific treatment because of tumor bleeding.

PMID- 25767675
TI  - [Lymph node tuberculosis: epidemiology, diagnostic and therapeutic aspects, about
      357 cases].

PMID- 25767676
TI  - [Place of intraoperative isotopic markers in the management of osteoid osteoma].

PMID- 25767677
TI  - Cancer metabolism: strategic diversion from targeting cancer drivers to targeting
      cancer suppliers.
AB  - Drug development groups are close to discovering another pot of gold-a
      therapeutic target-similar to the success of imatinib (Gleevec) in the field of
      cancer biology. Modern molecular biology has improved cancer therapy through the
      identification of more pharmaceutically viable targets, and yet major problems
      and risks associated with late-phase cancer therapy remain. Presently, a growing
      number of reports have initiated a discussion about the benefits of metabolic
      regulation in cancers. The Warburg effect, a great discovery approximately 70
      years ago, addresses the "universality" of cancer characteristics. For instance,
      most cancer cells prefer aerobic glycolysis instead of mitochondrial respiration.
      Recently, cancer metabolism has been explained not only by metabolites but also
      through modern molecular and chemical biological techniques. Scientists are
      seeking context-dependent universality among cancer types according to metabolic
      and enzymatic pathway signatures. This review presents current cancer metabolism
      studies and discusses future directions in cancer therapy targeting bio
      energetics, bio-anabolism, and autophagy, emphasizing the important contribution
      of cancer metabolism in cancer therapy. 

PMID- 25767678
TI  - Shikonin Isolated from Lithospermum erythrorhizon Downregulates Proinflammatory
      Mediators in Lipopolysaccharide-Stimulated BV2 Microglial Cells by Suppressing
      Crosstalk between Reactive Oxygen Species and NF-kappaB.
AB  - According to the expansion of lifespan, neuronal disorder based on inflammation
      has been social problem. Therefore, we isolated shikonin from Lithospermum
      erythrorhizon and evaluated anti-inflammatory effects of shikonin in
      lipopolysaccharide (LSP)-stimulated BV2 microglial cells. Shikonin dose
      dependently inhibits the expression of the proinflammatory mediators, nitric
      oxide (NO), prostaglandin E2 (PGE2), and tumor necrosis factor-alpha (TNF-alpha)
      as well as their main regulatory genes and products such as inducible NO synthase
      (iNOS), cyclooxygenase-2 (COX-2), and TNF-alpha in LPS-stimulated BV2 microglial
      cells. Additionally, shikonin suppressed the LPS-induced DNA-binding activity of
      nuclear factor-kappaB (NF-kappaB) to regulate the key regulatory genes of the
      proinflammatory mediators, such as iNOS, COX-2, and TNF-alpha, accompanied with
      downregulation of reactive oxygen species (ROS) generation. The results indicate
      that shikonin may downregulate the expression of proinflammatory genes involved
      in the synthesis of NO, PGE2, and TNF-alpha in LPS-treated BV2 microglial cells
      by suppressing ROS and NF-kappaB. Taken together, our results revealed that
      shikonin exerts downregulation of proinflammatory mediators by interference the
      ROS and NF-kappaB signaling pathway. 

PMID- 25767679
TI  - Inhibitory Effect of 3-(4-Hydroxyphenyl)-1-(thiophen-2-yl) prop-2-en-1-one, a
      Chalcone Derivative on MCP-1 Expression in Macrophages via Inhibition of ROS and
      Akt Signaling.
AB  - Chalcones (1,3-diaryl-2-propen-1-ones), a subfamily of flavonoid, are widely
      known to possess potent anti-inflammatory and anti-oxidant properties. In this
      study, we investigated the effect of 3-(4-Hydroxyphenyl)-1-(thio3-(4
      Hydroxyphenyl phen-2-yl)prop-2-en-1-one (TI-I-175), a synthetic chalcone
      derivative, on endotoxin-induced expression of monocyte chemoattractant protein-1
      (MCP-1), one of the key chemokines that regulates migration and infiltration of
      immune cells, and its potential mechanisms. TII-175 potently inhibited MCP-1 mRNA
      expression stimulated by lipopolysaccharide (LPS) in RAW 264.7 macrophages
      without significant effect on cell viability. Treatment of cells with TI-I-175
      markedly prevented LPS-induced transcriptional activation of activator protein-1
      (AP-1) as measured by luciferase reporter assay, while nuclear factor-kappaB (NF
      kappaB) activity was not inhibited by TI-I-175, implying that TI-I-175 suppressed
      MCP-1 expression probably via regulation of AP-1. In addition, TI-I-175 treatment
      significantly inhibited LPS-induced Akt phosphorylation and led to a significant
      decrease in reactive oxygen species (ROS) production by LPS, which act as up
      stream signaling events required for AP-1 activation in RAW 264.7 macrophages.
      Taken together, these results indicate that TI-I-175 suppresses MCP-1 gene
      expression in LPS-stimulated RAW 264.7 macrophages via suppression of ROS
      production and Akt activation. 

PMID- 25767680
TI  - The Cytotoxicity of Kahweol in HT-29 Human Colorectal Cancer Cells Is Mediated by
      Apoptosis and Suppression of Heat Shock Protein 70 Expression.
AB  - Although coffee is known to have antioxidant, anti-inflammatory, and antitumor
      properties, there have been few reports about the effect and mechanism of coffee
      compounds in colorectal cancer. Heat shock proteins (HSPs) are molecular
      chaperones that prevent cell death. Their expression is significantly elevated in
      many tumors and is accompanied by increased cell proliferation, metastasis and
      poor response to chemotherapy. In this study, we investigated the cytotoxicity of
      four bioactive compounds in coffee, namely, caffeine, caffeic acid, chlorogenic
      acid, and kahweol, in HT-29 human colon adenocarcinoma cells. Only kahweol showed
      significant cytotoxicity. Specifically, kahweol increased the expression of
      caspase-3, a pro-apoptotic factor, and decreased the expression of anti-apoptotic
      factors, such as Bcl-2 and phosphorylated Akt. In addition, kahweol significantly
      attenuated the expression of HSP70. Inhibition of HSP70 activity with triptolide
      increased kahweol-induced cytotoxicity. In contrast, overexpression of HSP70
      significantly reduced kahweol-induced cell death. Taken together, these results
      demonstrate that kahweol inhibits colorectal tumor cell growth by promoting
      apoptosis and suppressing HSP70 expression. 

PMID- 25767681
TI  - ATF3 Mediates Anti-Cancer Activity of Trans-10, cis-12-Conjugated Linoleic Acid
      in Human Colon Cancer Cells.
AB  - Conjugated linoleic acids (CLA) are a family of isomers of linoleic acid. CLA
      increases growth arrest and apoptosis of human colorectal cancer cells through an
      isomer-specific manner. ATF3 belongs to the ATF/CREB family of transcription
      factors and is associated with apoptosis in colorectal cancer. The present study
      was performed to investigate the molecular mechanism by which t10, c12-CLA
      stimulates ATF3 expression and apoptosis in human colorectal cancer cells. t10,
      c12-CLA increased an apoptosis in human colorectal cancer cells in dose dependent
      manner. t10, c12-CLA induced ATF3 mRNA and luciferase activity of ATF3 promoter
      in a dose-dependent manner. The responsible region for ATF3 transcriptional
      activation by t10, c12-CLA is located between -147 and -1850 of ATF3 promoter.
      mRNA stability of ATF3 was not affected by t10, c12-CLA treatment. t10, c12-CLA
      increases GSK3beta expression and suppresses IGF-1-stimulated phosphorylation of
      Akt. The knockdown of ATF3 suppressed expression of GSK3beta and NAG-1 and PARP
      cleavage. The results suggest that t10, c12-CLA induces apoptosis through ATF3
      mediated pathway in human colorectal cancer cells. 

PMID- 25767682
TI  - Cardamonin Suppresses TGF-beta1-Induced Epithelial Mesenchymal Transition via
      Restoring Protein Phosphatase 2A Expression.
AB  - Epithelial mesenchymal transition (EMT) is the first step in metastasis and
      implicated in the phenotype of cancer stem cells. Therefore, understanding and
      controlling EMT, are essential to the prevention and cure of metastasis. In the
      present study, we examined, by Western blot, reverse transcription polymerase
      chain reaction (RT-PCR), and confocal microscopy, the effects of cardamonin (CDN)
      on transforming growth factor-beta1 (TGF-beta1)-induced EMT of A549 lung
      adenocarcinoma cell lines. TGF-beta1 induced expression of N-cadherin and
      decreased expression of E-cadherin. CDN suppressed N-cadherin expression and
      restored E-cadherin expression. Further, TGF-beta1 induced migration and invasion
      of A549 cancer cells, which was suppressed by CDN. TGF-beta1 induced c-Jun N
      terminal kinase (JNK) activation during EMT, but CDN blocked it. Protein
      serine/threonine phosphatase 2A (PP2A) expression in A549 cancer cells was
      reduced by TGF-beta1 but CDN restored it. The overall data suggested that CDN
      suppresses TGF-beta1-induced EMT via PP2A restoration, making it a potential new
      drug candidate that controls metastasis. 

PMID- 25767683
TI  - Inhibitory effects of yuzu and its components on human platelet aggregation.
AB  - Our previous study demonstrated that yuzu has an anti-platelet effect in rat
      blood. In the present study, we examined whether the anti-platelet effect of yuzu
      can be extended to human blood by investigating its ability to inhibit
      aggregations induced by various agonists in human platelet rich plasma (PRP).
      This study also investigated the underlying mechanism of yuzu focusing on ADP
      granule secretion, TXB2 formations, and PLCgamma/Akt signaling. The results from
      this study showed that ethanolic yuzu extract (YE), and its components,
      hesperidin and naringin, inhibited human platelet aggregation in a concentration
      dependent manner. YE, hesperidin and naringin also inhibited TXB2 formation and
      ADP release. The phosphorylation of PLCgamma and Akt was significantly inhibited
      by YE, heperidin and naringin. Furthermore, we demonstrated that YE, heperidin
      and naringin has anti-platelet effects in rat ex vivo studies, and lower side
      effects in mice tail bleeding time studies. The results from this study suggest
      that YE, hesperidin and naringin can inhibit human platelet aggregation, at least
      partly through the inhibition of PLCgamma and Akt, leading to a decrease in TXB2
      formation and granule secretion. 

PMID- 25767684
TI  - Spinosin, a C-Glucosylflavone, from Zizyphus jujuba var. spinosa Ameliorates
      Abeta1-42 Oligomer-Induced Memory Impairment in Mice.
AB  - Alzheimer's disease (AD) is a neurodegenerative disorder associated with
      progressive memory loss and neuronal cell death. Although numerous previous
      studies have been focused on disease progression or reverse pathological
      symptoms, therapeutic strategies for AD are limited. Alternatively, the
      identification of traditional herbal medicines or their active compounds has
      received much attention. The aims of the present study were to characterize the
      ameliorating effects of spinosin, a C-glucosylflavone isolated from Zizyphus
      jujuba var. spinosa, on memory impairment or the pathological changes induced
      through amyloid-beta1-42 oligomer (AbetaO) in mice. Memory impairment was induced
      by intracerebroventricular injection of AbetaO (50 MUM) and spinosin (5, 10, and
      20 mg/kg) was administered for 7 days. In the behavioral tasks, the subchronic
      administration of spinosin (20 mg/kg, p.o.) significantly ameliorated AbetaO
      induced cognitive impairment in the passive avoidance task or the Y-maze task. To
      identify the effects of spinosin on the pathological changes induced through
      AbetaO, immunohistochemistry and Western blot analyses were performed. Spinosin
      treatment also reduced the number of activated microglia and astrocytes observed
      after AbetaO injection. In addition, spinosin rescued the AbetaO-induced decrease
      in choline acetyltransferase expression levels. These results suggest that
      spinosin ameliorated memory impairment induced through AbetaO, and these effects
      were regulated, in part, through neuroprotective activity via the anti
      inflammatory effects of spinosin. Therefore, spinosin might be a useful agent
      against the amyloid b protein-induced cognitive dysfunction observed in AD
      patients. 

PMID- 25767685
TI  - Galangin (3,5,7-trihydroxyflavone) shields human keratinocytes from ultraviolet B
      induced oxidative stress.
AB  - Most skin damage caused by ultraviolet B (UVB) radiation is owing to the
      generation of reactive oxygen species. Phytochemicals can act as antioxidants
      against UVB-induced oxidative stress. This study investigated the protective
      effects of the flavone galangin against UVB-induced oxidative damage in human
      keratinocytes. Galangin efficiently scavenged free radicals and reduced UVB
      induced damage to cellular macromolecules, such as DNA, lipids, and proteins.
      Furthermore, galangin rescued cells undergoing apoptosis induced by UVB radiation
      via recovering mitochondrial polarization and down-regulating apoptotic proteins.
      These results showed that galangin protects human keratinocytes against UVB
      radiation-induced cellular damage and apoptosis via its antioxidant effects. 

PMID- 25767686
TI  - Hair growth promoting potential of phospholipids purified from porcine lung
      tissues.
AB  - BP201, porcine lung tissue-derived phospholipids, consists of phosphatidylcholine
      as a major phospholipid species. BP201 promoted hair growth after application
      onto the shaved backs of BALB/c and C3H mice. Its effect was enhanced when
      applied together with minoxidil (MNX) in C3H mice. When the tissue specimens
      prepared from the shaved skins of BP201-treated and control mice were
      microscopically examined, the total numbers of hair follicles in both anagen and
      telogen phases of BP201-treated mice were significantly higher than those of
      control mice. The numbers of hair follicles in the anagen phase of BP201-treated
      mice were also higher than those of control mice. In combination with MNX, BP201
      further increased the total number of hair follicles, but did not alter the
      percentage of hair follicles in the anagenic phase. BP201 also increased the
      proliferation of human hair follicle dermal papilla cells. Collectively, BP201
      possesses hair growth promoting potential, which would suggest its use singly or
      in combination for hair growth products. 

PMID- 25767687
TI  - Diallyl Disulfide Prevents Cyclophosphamide-Induced Hemorrhagic Cystitis in Rats
      through the Inhibition of Oxidative Damage, MAPKs, and NF-kappaB Pathways.
AB  - This study investigated the possible effects and molecular mechanisms of diallyl
      disulfide (DADS) against cyclophosphamide (CP)-induced hemorrhagic cystitis (HC)
      in rats. Inflammation response was assessed by histopathology and serum cytokines
      levels. We determined the protein expressions of nuclear transcription factor
      kappa-B (NF-kappaB), inducible nitric oxide synthase (iNOS), cyclooxygenase-2
      (COX-2), and tumor necrosis factor-alpha (TNF-alpha), oxidative stress, urinary
      nitrite-nitrate, malondialdehyde (MDA), and 8-hydroxy-2'-deoxyguanosine (8-OHdG).
      Finally, we studied the involvement of mitogen-activated protein kinases (MAPKs)
      signaling in the protective effects of DADS against CP-induced HC. CP treatment
      caused a HC which was evidenced by an increase in histopathological changes,
      proinflammatory cytokines levels, urinary nitrite-nitrate level, and the protein
      expression of NF-kappaB, COX-2, iNOS, TNF-alpha, p-c-Jun N-terminal kinase (JNK),
      and p-extracellular signal regulated kinase (ERK). The significant decreases in
      glutathione content and glutathione-S-transferase and glutathione reductase
      activities, and the significant increase in MDA content and urinary MDA and 8
      OHdG levels indicated that CP-induced bladder injury was mediated through
      oxidative DNA damage. In contrast, DADS pretreatment attenuated CP-induced HC,
      including histopathological lesion, serum cytokines levels, oxidative damage, and
      urinary oxidative DNA damage. DADS also caused significantly decreased the
      protein expressions of NF-kappaB, COX-2, iNOS, TNF-alpha, p-JNK, and p-ERK. These
      results indicate that DADS prevents CP-induced HC and that the protective effects
      of DADS may be due to its ability to regulate proinflammatory cytokines
      production by inhibition of NF-kappaB and MAPKs expressions, and its potent anti
      oxidative capability through reduction of oxidative DNA damage in the bladder. 

PMID- 25767688
TI  - Functional Significance of Cytochrome P450 1A2 Allelic Variants, P450 1A2*8, *15,
      and *16 (R456H, P42R, and R377Q).
AB  - P450 1A2 is responsible for the metabolism of clinically important drugs and the
      metabolic activation of environmental chemicals. Genetic variations of P450 1A2
      can influence its ability to perform these functions, and thus, this study aimed
      to characterize the functional significance of three P450 1A2 allelic variants
      containing nonsynonymous single nucleotide polymorphisms (P450 1A2*8, R456H; *15,
      P42R; *16, R377Q). Variants containing these SNPs were constructed and the
      recombinant enzymes were expressed and purified in Escherichia coli. Only the
      P42R variant displayed the typical CO-binding spectrum indicating a P450
      holoenzyme with an expression level of ~ 170 nmol per liter culture, but no P450
      spectra were observed for the two other variants. Western blot analysis revealed
      that the level of expression for the P42R variant was lower than that of the wild
      type, however the expression of variants R456H and R377Q was not detected. Enzyme
      kinetic analyses indicated that the P42R mutation in P450 1A2 resulted in
      significant changes in catalytic activities. The P42R variant displayed an
      increased catalytic turnover numbers (k cat) in both of methoxyresorufin O
      demethylation and phenacetin O-deethylation. In the case of phenacetin O
      deethylation analysis, the overall catalytic efficiency (k cat/K m) increased up
      to 2.5 fold with a slight increase of its K m value. This study indicated that
      the substitution P42R in the N-terminal proline-rich region of P450 contributed
      to the improvement of catalytic activity albeit the reduction of P450 structural
      stability or the decrease of substrate affinity. Characterization of these
      polymorphisms should be carefully examined in terms of the metabolism of many
      clinical drugs and environmental chemicals. 

PMID- 25767689
TI  - Effect of methotrexate on collagen-induced arthritis assessed by micro-computed
      tomography and histopathological examination in female rats.
AB  - We tested the hypothesis that micro-computed tomography (micro-CT) analysis
      provides a better quantitative readout of the therapeutic potential of
      methotrexate (MTX) for treating collagen-induced arthritis (CIA) in rats and
      compared to conventional histopathological examination. Rats were divided into
      three groups: Group 1 (G1) was treated with 0.9% saline, whereas groups 2 (G2)
      and 3 (G3) were boosted with type II collagen at days 0 and 7. Following the
      first collagen immunization, rats in G1 and G2 were treated with 0.9% saline and
      those in G3 were treated with 1.5 mg/kg MTX from day 14 to 28. All rats were
      sacrificed on day 28, at which point and all hind knee joints were analyzed by
      micro-CT and histopathological examination. Micro-CT analyses showed that bone
      volume and trabecular number were significantly decreased in G2 and G3 compared
      to G1 (p<0.01), as was percent bone volume (p<0.05 and p<0.01, respectively).
      However, bone surface/bone volume was significantly increased in G2 and G3
      compared to G1 (p<0.05 and p<0.01, respectively). Trabecular separation was
      significantly increased in G3 compared to G1 (p<0.05). Histopathological
      examination showed that knee joints of rats in G2 and G3 showed severe joint
      destruction with inflammatory cell infiltration. However, cartilage destruction
      was slightly reduced in G3 compared to G2. Taken together, these results suggest
      that MTX treatment reduced cartilage destruction in rats with CIA, and micro-CT
      analyses made it possible to quantify arthritic bony lesion. 

PMID- 25767690
TI  - Effects of baicalin on oral pharmacokinetics of caffeine in rats.
AB  - Scutellaria baicalensis is one of the most widely used herbal medicines in East
      Asia. Because baicalein and baicalin are major components of this herb, it is
      important to understand the effects of these compounds on drug metabolizing
      enzymes, such as cytochrome P450 (CYP), for evaluating herb-drug interaction. The
      effects of baicalin and baicalein on activities of ethoxyresorufin O-deethylase
      (EROD), methoxyresorufin O-demethylase (MROD), benzyloxyresorufin O-debenzylase
      (BROD), p-nitrophenol hydroxylase and erythromycin N-demethylase were assessed in
      rat liver microsomes in the present study. In addition, the pharmacokinetics of
      caffeine and its three metabolites (i.e., paraxanthine, theobromine and
      theophylline) in baicalin-treated rats were compared with untreated control. As
      results, EROD, MROD and BROD activities were inhibited by both baicalin and
      baicalein. However, there were no significant differences in the pharmacokinetic
      parameters of oral caffeine and its three metabolites between control and
      baicalin-treated rats. When the plasma concentration of baicalin was determined,
      the maximum concentration of baicalin was below the estimated IC50 values
      observed in vitro. In conclusion, baicalin had no effects on the pharmacokinetics
      of caffeine and its metabolites in vivo, following single oral administration in
      rats. 

PMID- 25767692
TI  - Pulse splitter-based nonlinear microscopy for live-cardiomyocyte imaging.
AB  - Second harmonic generation (SHG) microscopy is a new imaging technique used in
      sarcomeric-addition studies. However, during the early stage of cell culture in
      which sarcomeric additions occur, the neonatal cardiomyocytes that we have been
      working with are very sensitive to photodamage, the resulting high rate of cell
      death prevents systematic study of sarcomeric addition using a conventional SHG
      system. To address this challenge, we introduced use of the pulse-splitter system
      developed by Na Ji et al. in our two photon excitation fluorescence (TPEF) and
      SHG hybrid microscope. The system dramatically reduced photodamage to neonatal
      cardiomyocytes in early stages of culture, greatly increasing cell viability.
      Thus continuous imaging of live cardiomyocytes was achieved with a stronger laser
      and for a longer period than has been reported in the literature. The pulse
      splitter-based TPEF-SHG microscope constructed in this study was demonstrated to
      be an ideal imaging system for sarcomeric addition-related investigations of
      neonatal cardiomyocytes in early stages of culture.

PMID- 25767691
TI  - A True Multi-modality Approach for High Resolution Optical Imaging: Photo
      Magnetic Imaging.
AB  - Multi-modality imaging leverages the competitive advantage of different imaging
      systems to improve the overall resolution and quantitative accuracy. Our new
      technique, Photo-Magnetic Imaging (PMI) is one of these true multi-modality
      imaging approaches, which can provide quantitative optical absorption map at MRI
      spatial resolution. PMI uses laser light to illuminate tissue and elevate its
      temperature while utilizing MR thermometry to measure the laser-induced
      temperature variation with high spatial resolution. The high-resolution
      temperature maps are later converted to tissue absorption maps by a finite
      element based inverse solver that is based on modeling of photon migration and
      heat diffusion in tissue. Previously, we have demonstrated the feasibility of PMI
      with phantom studies. Recently, we have managed to reduce the laser power under
      ANSI limit for maximum skin exposure therefore, we have well positioned PMI for
      in vivo imaging. Currently we are expanding our system by adding multi-wavelength
      imaging capability. This will allow us not only to resolve spatial distribution
      of tissue chromophores but also exogenous contrast agents. Although we test PMIs
      feasibility with animal studies, our future goal is to use PMI for breast cancer
      imaging due to its high translational potential.

PMID- 25767693
TI  - Fast fluorescence holographic microscopy.
AB  - FINCHSCOPE is a new technology of fluorescence holographic microscopy. It has
      been successfully applied to recording high-resolution three-dimensional
      fluorescence images of biological specimens without the need for scanning. In
      this study, we revealed and analyzed an intrinsic phenomenon, called ghost lens
      effect, on spatial light modulator which is the core element enabling the
      incoherent correlation in the FINCHSCOPE. The ghost lens effect can degrade the
      imaging quality by introducing multiple spherical waves with different focal
      lengths into the correlation and thus increasing the noise in the recorded
      holograms.

PMID- 25767695
TI  - Open peer review at four STEM journals: an observational overview.
AB  - Open peer review, peer review where authors' and reviewers' identities are
      disclosed to one another, is a growing trend in scholarly publishing. Through
      observation of four journals in STEM disciplines, PLoS One, Atmospheric Chemistry
      & Physics, PeerJ, and F1000Research, an observational overview is conducted. The
      overview relies on defined characteristics of open peer review. Results show that
      despite differing open peer review implementations, each journal retains
      editorial involvement in scholarly publishing. Further, the analysis shows that
      only one of these implementations is fully transparent in its peer review and
      decision making process. Finally, the overview contends that journals should
      clearly outline peer review and editorial processes in order to allow for open
      peer review to be better understood and adopted by authors, reviewers, editors,
      and readers of science communications. 

PMID- 25767694
TI  - K-core decomposition of a protein domain co-occurrence network reveals lower
      cancer mutation rates for interior cores.
AB  - BACKGROUND: Network biology currently focuses primarily on metabolic pathways,
      gene regulatory, and protein-protein interaction networks. While these approaches
      have yielded critical information, alternative methods to network analysis will
      offer new perspectives on biological information. A little explored area is the
      interactions between domains that can be captured using domain co-occurrence
      networks (DCN). A DCN can be used to study the function and interaction of
      proteins by representing protein domains and their co-existence in genes and by
      mapping cancer mutations to the individual protein domains to identify signals.
      RESULTS: The domain co-occurrence network was constructed for the human proteome
      based on PFAM domains in proteins. Highly connected domains in the central cores
      were identified using the k-core decomposition technique. Here we show that these
      domains were found to be more evolutionarily conserved than the peripheral
      domains. The somatic mutations for ovarian, breast and prostate cancer diseases
      were obtained from the TCGA database. We mapped the somatic mutations to the
      individual protein domains and the local false discovery rate was used to
      identify significantly mutated domains in each cancer type. Significantly mutated
      domains were found to be enriched in cancer disease pathways. However, we found
      that the inner cores of the DCN did not contain any of the significantly mutated
      domains. We observed that the inner core protein domains are highly conserved and
      these domains co-exist in large numbers with other protein domains. CONCLUSION:
      Mutations and domain co-occurrence networks provide a framework for understanding
      hierarchal designs in protein function from a network perspective. This study
      provides evidence that a majority of protein domains in the inner core of the DCN
      have a lower mutation frequency and that protein domains present in the
      peripheral regions of the k-core contribute more heavily to the disease. These
      findings may contribute further to drug development.

PMID- 25767696
TI  - Enhancement of COPD biological networks using a web-based collaboration
      interface.
AB  - The construction and application of biological network models is an approach that
      offers a holistic way to understand biological processes involved in disease.
      Chronic obstructive pulmonary disease (COPD) is a progressive inflammatory
      disease of the airways for which therapeutic options currently are limited after
      diagnosis, even in its earliest stage. COPD network models are important tools to
      better understand the biological components and processes underlying initial
      disease development. With the increasing amounts of literature that are now
      available, crowdsourcing approaches offer new forms of collaboration for
      researchers to review biological findings, which can be applied to the
      construction and verification of complex biological networks. We report the
      construction of 50 biological network models relevant to lung biology and early
      COPD using an integrative systems biology and collaborative crowd-verification
      approach. By combining traditional literature curation with a data-driven
      approach that predicts molecular activities from transcriptomics data, we
      constructed an initial COPD network model set based on a previously published non
      diseased lung-relevant model set. The crowd was given the opportunity to enhance
      and refine the networks on a website ( https://bionet.sbvimprover.com/) and to
      add mechanistic detail, as well as critically review existing evidence and
      evidence added by other users, so as to enhance the accuracy of the biological
      representation of the processes captured in the networks. Finally, scientists and
      experts in the field discussed and refined the networks during an in-person
      jamboree meeting. Here, we describe examples of the changes made to three of
      these networks: Neutrophil Signaling, Macrophage Signaling, and Th1-Th2
      Signaling. We describe an innovative approach to biological network construction
      that combines literature and data mining and a crowdsourcing approach to generate
      a comprehensive set of COPD-relevant models that can be used to help understand
      the mechanisms related to lung pathobiology. Registered users of the website can
      freely browse and download the networks. 

PMID- 25767697
TI  - A case study evaluation of competitors undertaking an antarctic ultra-endurance
      event: nutrition, hydration and body composition variables.
AB  - BACKGROUND: The nutritional demands of ultra-endurance racing are well
      documented. However, the relationship between nutritional consumption and
      performance measures are less obvious for athletes competing in Polar conditions.
      Therefore, the aim of this study was to evaluate dietary intake, hydration
      status, body composition and performance times throughout an 800-km Antarctic
      race. METHODS: The event organisers declared that 17 competitors would
      participate in the South Pole race. Of the 17 competitors, pre-race data were
      collected from 13 participants (12 males and 1 female (M +/- SD): age: 40.1 +/-
      8.9 years; weight: 83.9 +/- 10.3 kg; and body fat percentage: 21.9 +/- 3.8%).
      Dietary recall, body composition and urinary osmolarity were assessed pre-race,
      midway checkpoint and end race. Data were compared on the basis of fast finishers
      (the Norwegian team (n = 3) who won in a record of 14 days) and slower finishers
      (the remaining teams (n = 10) reaching the South Pole between 22 and 28 days).
      RESULTS: The percentage contribution of macronutrients to daily energy intake for
      all participants was as follows: carbohydrate (CHO) = 23.7% (221 +/- 82 g.day(
      1)), fat = 60.6% (251 +/- 127 g.day(-1)) and protein = 15.7% (117 +/- 52 g.day(
      1)). Energy demands were closer met by faster finishers compared to slower
      finishers (5,332 +/- 469 vs. 3,048 +/- 1,140 kcal.day(-1), p = 0.02). Average
      reduction in body mass throughout the race was 8.3 +/- 5.5 kg, with an average
      loss of lean mass of 2.0 +/- 4.1 kg. There was a significant negative correlation
      between changes in lean mass and protein intake (p = 0.03), and lean mass and
      energy intake (p = 0.03). End-race urinary osmolarity was significantly elevated
      for faster finishers compared to slower finishers and control volunteers (faster
      finishers: 933 +/- 157 mOsmol.L(-1); slower finishers: 543 +/- 92 mOsmol.L(-1);
      control: 515 +/- 165 mOsmol.L(-1), p = 0.04). CONCLUSIONS: Throughout the race,
      both groups were subjected to a negative change in energy balance which partly
      explained reduced body mass. Carbohydrate availability was limited inferring a
      greater reliance on fat and protein metabolism. Consequently, loss in fat-free
      mass was more prevalent with insufficient protein and caloric intake, which may
      relate to performance.

PMID- 25767698
TI  - Career perspective: Alf O. Brubakk-looking back to see ahead.
AB  - The following describes my professional life up till today, but it also describes
      what I think lies ahead. I have led an interesting professional life and been
      lucky enough to be at the centre of some of the important development in modern
      medicine and diving, namely ultrasound in cardiology and the mechanisms of
      decompression. I therefore should be able to see some of the most challenging and
      exciting problems ahead. Ultrasound in cardiology has developed from simply
      listening to the Doppler signal to determine the velocity of blood flow to the
      complicated description of images presented today. Diving, in addition to being
      an important commercial and environmental activity, exposes the individual to
      intermittent hyperoxia and pressure reductions. These challenges evoke the
      production of radical oxygen species (ROS) and microparticles (MP) that also are
      central to many pathophysiologic mechanisms that are involved in a number of
      severe human diseases. Thus, diving can be regarded as an important model of
      disease and allows us to study their effects on healthy young individuals. The
      future thus points towards an integration of environmental physiology with
      detailed physiological and pathophysiological mechanisms and makes diving
      physiology a potentially very important field of study. 

PMID- 25767699
TI  - Tumoral calcinosis in a patient with hypoparathyroidism, sensorineural deafness,
      and renal dysplasia syndrome undergoing hemodialysis.
AB  - We describe a hemodialysis patient with hypoparathyroidism due to HDR
      (hypoparathyroidism, sensorineural deafness, and renal dysplasia) syndrome caused
      by GATA3 mutation. She presents tumoral calcinosis which is a rare complication
      of end-stage renal failure. A novel mutation of GATA3 is identified in this
      patient. 

PMID- 25767701
TI  - (18)F-Fluorine-18-l-dihydroxyphenylalanine ((18)F-DOPA) positive isolated
      peritoneal carcinomatosis from a MENII-related medullary thyroid carcinoma. About
      an atypical metastatic site and utility of (18)F-FDOPA.
AB  - A patient, operated for a medullary thyroid carcinoma (MTC) with a positive RET
      mutation, showed several peritoneal nodes on a computed tomography (CT), with
      increased Thyrocalcitonine. A (18)F-Fluorine-18-l-dihydroxyphenylalanine (18-F
      FDOPA) positron emission tomography (PET/CT) showed isolated tracer uptake on the
      nodes. A biopsy confirmed that it was from the MTC, with the same RET mutation as
      in blood. 

PMID- 25767700
TI  - A very rare case of primary meningococcal arthritis in an adult male.
AB  - We report here a very rare case of primary meningococcal arthritis of the knee
      joint without clinical features associated with meningococcemia, meningitis, or
      meningococcal complications. The patient suffered from diabetes mellitus and had
      experienced two episodes of joint trauma. Intravenous infusion of
      ampicillin/sulbactam for 18 consecutive days was successful. 

PMID- 25767702
TI  - Meningeal involvement in multiple myeloma.
AB  - A patient with multiple myeloma with a mass in the nasopharyngeal was diagnosed.
      He received melphalan autograft and radiotherapy, and obtained complete
      remission. He relapsed 3 months later, with meningeal involvement and without
      systemic relapse. He received intrathecal and systemic chemotherapy, without
      neurological improvement and died 4 weeks after relapse. 

PMID- 25767703
TI  - Increased eculizumab requirements during pregnancy in a patient with paroxysmal
      nocturnal hemoglobinuria: case report and review of the literature.
AB  - Paroxysmal nocturnal hemoglobinuria (PNH) results from reduced complement
      regulatory proteins on hematopoietic cells, predisposing patients to
      intravascular hemolysis, thrombophilia, and cytopenias. Women diagnosed in
      pregnancy can experience significant maternofetal complications. Trials of
      eculizumab in PNH excluded pregnant women. Here, we report the first Canadian
      patient taken through pregnancy on eculizumab. 

PMID- 25767704
TI  - Prenatal diagnosis of trisomy 6q25.3-qter and monosomy 10q26.12-qter by array CGH
      in a fetus with an apparently normal karyotype.
AB  - We present the prenatal case of a 12.5-Mb duplication involving 6q25-qter and a
      12.2-Mb deletion encompassing 10q26-qter diagnosed by aCGH, while conventional
      karyotype showed normal results. The genotype-phenotype correlation between
      individual microarray and clinical findings adds to the emerging atlas of
      chromosomal abnormalities associated with specific prenatal ultrasound
      abnormalities. 

PMID- 25767705
TI  - A case of metastasis-induced acute pancreatitis in a patient with small cell lung
      cancer.
AB  - We report a rare case of metastasis-induced acute pancreatitis (MIAP) from small
      cell lung cancer (SCLC) diagnosed on autopsy, indicating a diagnosis of MIAP with
      SCLC. Our case suggests that MIAP can arise as a complication of SCLC and has an
      extremely poor prognosis. 

PMID- 25767706
TI  - Soft-tissue tumor of the perineum: an exceptional case of bilateral perineal
      myoma.
AB  - Perineal myomas in female are exceptional. We report the second case in
      literature of perineal myomas. It is a case of bilateral perineal myomas lifting
      the skin occurring in a female patient of 49 years old. She was operated by
      perineal incisions. Histopathology confirmed the fibromatous nature without signs
      of malignancy. 

PMID- 25767707
TI  - Thyrotoxic hypokalemic periodic paralysis in an African male: a case report.
AB  - Thyrotoxic hypokalemic periodic paralysis is a rare manifestation of
      thyrotoxicosis and is rarely reported in non-Asian populations. A 26-year-old
      Ethiopian male who presented with recurrent flaccid tetraparesis, hypokalemia,
      and hyperthyroidism is reported here. Thyroid function should be routinely
      checked in patients with acute or recurrent hypokalemic paralysis. 

PMID- 25767708
TI  - Prenatal diagnosis of pyriform sinus fistula: case report and literature review.
AB  - We describe a case of prenatal diagnosis of a pharyngeal cyst as a pyriform sinus
      fistula on the findings of ultrasonography and magnetic resonance imaging. 

PMID- 25767709
TI  - A case report of de novo missense FOXP1 mutation in a non-Caucasian patient with
      global developmental delay and severe speech impairment.
AB  - The FOXP protein family (FOXP1-4) is a group of transcription factors that play
      important roles in embryological, immunological, hematological, and speech and
      language development. Here, we report FOXP1 de novo mutation and severe speech
      delay in an individual belonging to a non-Caucasian population. 

PMID- 25767710
TI  - Molecular prenatal diagnosis of megalencephalic leukoencephalopathy with
      subcortical cysts in a child from southwest of Iran.
AB  - Megalencephalic leukoencephalopathy (MLC) is a rare neurological disorder with an
      autosomal recessive pattern. Clinical diagnosis was based on macrocephaly,
      recurrent seizure, and magnetic resonance imaging (MRI). Here we report first
      finding of a novel homozygous single base deletion in the MLC1 gene in an
      affected Iranian child causing a premature stop codon (p.L150fs.160X). 

PMID- 25767711
TI  - An unusual case of phenotype switch between AML FAB subtypes.
AB  - Phenotypic switch between any leukemia subtypes is of concern to a treating
      physician and more so, in acute myelocytic leukemia (AML) as the mechanisms for
      switch and subsequent chemotherapy regimen to be used remain unclear. AML-non-M3
      from AML-M3 subtype needs special mention as this has been unheard off. 

PMID- 25767712
TI  - Toxic epidermal necrolysis and hemophagocytic lymphohistiocytosis: a case report
      and literature review.
AB  - Diagnostic criteria for hemophagocytic lymphohistiocytosis should be reviewed
      early in critically ill patients with toxic epidermal necrolysis, multisystem
      dysfunction, and a deteriorating clinical trajectory. 

PMID- 25767713
TI  - Angiotensin-converting enzyme inhibitors-induced angioedema treated by C1
      esterase inhibitor concentrate (Berinert(r)): about one case and review of the
      therapeutic arsenal.
AB  - C1 esterase inhibitor (Berinert(r)) is generally used to treat severe attack of
      hereditary angioedema. We describe here the case of a patient who presented with
      a severe angioedema induced by angiotensin-converting enzyme inhibitors (ACEIs)
      endangering her life. It could be successfully treated with that medicine. 

PMID- 25767714
TI  - Snapshot in surgery: intraperitoneal encapsulated fat necrosis.
AB  - A 66-year-old man with rectal cancer was found to have an incidental ring-like
      lesion in the left rectovesical pouch. Histology revealed an encapsulated fat
      necrosis. Intraperitoneal encapsulated fat necroses are postulated to be a result
      of infarcted epiploic appendages resulting in a free-floating lesion. 

PMID- 25767716
TI  - Programmed death ligand-1 expression in adrenocortical carcinoma: an exploratory
      biomarker study.
AB  - BACKGROUND: Adrenocortical carcinoma (ACC) is a rare tumor in which prognostic
      factors are still not well established. Programmed Death Ligand-1 (PD-L1)
      expression in ACC and its association with clinico-pathological features and
      survival outcomes are unknown. METHODS: Formalin-fixed paraffin-embedded (FFPE)
      specimens were obtained from 28 patients with ACC. PD-L1 expression was evaluated
      by immunohistochemistry (IHC) in both tumor cell membrane and tumor infiltrating
      mononuclear cells (TIMC). PD-L1 positivity on tumor cells was defined as >=5%
      tumor cell membrane staining. TIMC were evaluated by IHC using a CD45 monoclonal
      antibody. For PD-L1 expression in TIMC, a combined score based on the extent of
      infiltrates and percentage of positive cells was developed. Any score greater
      that zero was considered PD-L1 positive. Baseline clinico-pathological
      characteristics and follow up data were retrospectively collected. Comparisons
      between PD-L1 expression and clinico-pathological features were evaluated using
      unpaired t-test and Fisher's exact test. Kaplan-Meier method and log-rank test
      were used to assess association between PD-L1 expression and 5-year overall
      survival (OS). RESULTS: Among 28 patients with surgically treated ACC, 3 (10.7%)
      were considered PD-L1 positive on tumor cell membrane. On the other hand, PD-L1
      expression in TIMC was performed in 27 specimens and PD-L1 positive staining was
      observed in 19 (70.4%) patients. PD-L1 positivity in either tumor cell membrane
      or TIMC was not significantly associated with higher stage at diagnosis, higher
      tumor grade, excessive hormone secretion, or OS. CONCLUSIONS: PD-L1 expression
      can exist in ACC in both tumor cell membrane and TIMC with no relationship to
      clinico-pathologic parameters or survival.

PMID- 25767717
TI  - Work-related COPD after years of occupational exposure.
AB  - BACKGROUND: Cigarette smoking is known as the most important risk factor of
      chronic obstructive pulmonary disease (COPD). However, occupational exposure to
      other substances can result in COPD. CASE REPORT: A 76-year-old man with
      occupational exposures to mixtures of silica dust, gas, and fumes for 10 years
      and with a 25 pack-year smoking history was diagnosed with COPD. His computed
      tomogram scan revealed some hyperinflation with emphysematous change in both
      upper lobes. In the pulmonary function tests, his post-bronchodilator forced
      vital capacity (FVC), forced expiratory volume in one second (FEV1), and
      FEV1/FVC% were 2.20 L (67% of the predicted value), 1.12 L (52% of the predicted
      value), and 51%, respectively, indicating moderate COPD. This case of COPD was
      confirmed as a work-related disease by the Occupational Lung Disease Research
      Institute in Korea Workers' Compensation & Welfare Service. CONCLUSION: Exposure
      to various substances such as silica dust, gas, and fumes from furnace and boiler
      installation was likely the cause of COPD in this patient. Thus, occupational
      exposure should be considered an important risk factor of COPD.

PMID- 25767718
TI  - Bacterial infections in patients with type 1 diabetes: a 14-year follow-up study.
AB  - OBJECTIVE: This study explored the annual occurrence/incidence of bacterial
      infections, and their association with chronic hyperglycemia and diabetic
      nephropathy, in patients with type 1 diabetes. DESIGN: In a register-based follow
      up study, we investigated the frequency of bacterial infections in patients with
      type 1 diabetes (n=4748) and age-matched and sex-matched non-diabetic control
      (NDC) subjects (n=12 954) using nationwide register data on antibiotic drug
      prescription purchases and hospital discharge diagnoses, collected between 1996
      and 2009. Diabetic nephropathy was classified based on the urinary albumin
      excretion rate (AER). RESULTS: The hospitalization rate due to bacterial
      infections was higher in patients with diabetes compared with NDCs (rate ratio
      (RR) 2.30 (95% CI 2.11 to 2.51)). The rate correlated with the severity of
      diabetic nephropathy: RR for microalbuminuria was 1.23 (0.94 to 1.60), 1.97 (1.49
      to 2.61) for macroalbuminuria, 11.2 (8.1 to 15.5) for dialysis, and 6.72 (4.92 to
      9.18) for kidney transplant as compared to patients with diabetes and normal AER.
      The annual number of antibiotic purchases was higher in patients with diabetes
      (1.00 (1.00 to 1.01)) as compared with NDCs (0.47 (0.46 to 0.47)), RR=1.71 (1.65
      to 1.77). Annual antibiotic purchases were 1.18-fold more frequent in patients
      with microalbuminuria, 1.29-fold with macroalbuminuria, 2.43-fold with dialysis,
      and 2.74-fold with kidney transplant as compared to patients with normal AER.
      Each unit of increase in glycated hemoglobin was associated with a 6-10% increase
      in the number of annual antibiotic purchases. CONCLUSIONS: The incidence of
      bacterial infections was significantly higher in patients with type 1 diabetes
      compared with age-matched and sex-matched NDC subjects, and correlated with the
      severity of diabetic nephropathy in inpatient and outpatient settings.

PMID- 25767719
TI  - Antibacterial and Antibiofilm Activities of Makaluvamine Analogs.
AB  - Streptococcus mutans is a key etiological agent in the formation of dental
      caries. The major virulence factor is its ability to form biofilms. Inhibition of
      S. mutans biofilms offers therapeutic prospects for the treatment and the
      prevention of dental caries. In this study, 14 analogs of makaluvamine, a marine
      alkaloid, were evaluated for their antibacterial activity against S. mutans and
      for their ability to inhibit S. mutans biofilm formation. All analogs contained
      the tricyclic pyrroloiminoquinone core of makaluvamines. The structural
      variations of the analogs are on the amino substituents at the 7-position of the
      ring and the inclusion of a tosyl group on the pyrrole ring N of the makaluvamine
      core. The makaluvamine analogs displayed biofilm inhibition with IC50 values
      ranging from 0.4 MUM to 88 MUM. Further, the observed bactericidal activity of
      the majority of the analogs was found to be consistent with the anti-biofilm
      activity, leading to the conclusion that the anti-biofilm activity of these
      analogs stems from their ability to kill S. mutans. However, three of the most
      potent N-tosyl analogs showed biofilm IC50 values at least an order of magnitude
      lower than that of bactericidal activity, indicating that the biofilm activity of
      these analogs is more selective and perhaps independent of bactericidal activity.

PMID- 25767720
TI  - The impact of migraine on posterior ocular structures.
AB  - Purpose. To investigate the thickness of the retinal nerve fiber layer (RNFL) and
      choroid in patients who have migraines in comparison to healthy controls.
      Methods. This study included 76 eyes and patients in the migraine group, 36 with
      aura (MWA group) and 40 without (MWoA group), and 38 eyes as control subjects.
      The RNFL and macular thicknesses were analysed with standard OCT protocol while
      choroidal thickness was analysed with EDI protocol in all subjects. Choroidal
      thickness was measured at the fovea, 1500 um nasal and 1500 um temporal to the
      fovea in a horizontal section. Results. The mean RNFL thickness for nasal and
      nasal inferior sectors was significantly thinner (P <= 0.018) in the migraineurs'
      eyes than in those of the controls, as was the mean choroid thickness at the
      fovea and measured points (P < 0.0001). However, the mean macular thickness was
      not significantly different between the groups. Conclusions. This study suggests
      that migraine leads to a reduction in the peripapillary RNFL thickness and to
      thinning in choroidal structures. These findings can be explained by a chronic
      ischemic insult related to migraine pathogenic mechanisms and these findings are
      considered supportive of the relationship between glaucoma and migraine. 

PMID- 25767721
TI  - Insects' RNA Profiling Reveals Absence of "Hidden Break" in 28S Ribosomal RNA
      Molecule of Onion Thrips, Thrips tabaci.
AB  - With an exception of aphids, insects' 28S rRNA is thought to harbor a "hidden
      break" which cleaves under denaturing conditions to comigrate with 18S rRNA band
      to exhibit a degraded appearance on native agarose gels. The degraded appearance
      confounds determination of RNA integrity in laboratories that rely on gel
      electrophoresis. To provide guidelines for RNA profiles, RNA from five major
      insect orders, namely, Diptera, Hemiptera, Thysanoptera, Hymenoptera, and
      Lepidoptera, was compared under denaturing and nondenaturing conditions. This
      study confirmed that although present in most of insect's RNA, the "hidden break"
      is absent in the 28S rRNA of onion thrips, Thrips tabaci. On the other hand,
      presence of "hidden break" was depicted in whiteflies' 28S rRNA despite their
      evolutionary grouping under same order with aphids. Divergence of 28S rRNA
      sequences confirms variation of both size and composition of gap region among
      insect species. However, phylogeny reconstruction does not support speciation as
      a possible source of the hidden break in insect's 28S rRNA. In conclusion, we
      show that RNA from a given insect order does not conform to a particular banding
      profile and therefore this approach cannot be reliably used to characterize newly
      discovered species. 

PMID- 25767722
TI  - Correlation between clinical characteristics and chest computed tomography
      findings of pulmonary cryptococcosis.
AB  - OBJECTIVE: The aim of this study was to review HIV-negative patients with
      pulmonary cryptococcosis to analyze the correlations between clinical
      characteristics and chest computed tomography (CT) findings. METHODS: We
      retrospectively analyzed medical records of 16 HIV-negative patients with
      pulmonary cryptococcosis diagnosed at our institution, and clinical
      characteristics of the patients with nodules or masses without ground-glass
      attenuation (GGA)/consolidation type were compared with those of patients with
      inclusive GGA or consolidation type. RESULTS: Host status was immunocompromised
      (81.2%) in most of the patients, and 6 (37.5%) were asymptomatic. The most
      frequent radiologic abnormalities on chest CT scans were one or more nodules
      (87.5%), GGA (37.5%), and consolidations (18.8%). Most lesions were located in
      the lower lung. Levels of hemoglobin and platelets were significantly lower in
      patients with inclusive GGA or consolidation type. Although the differences were
      not significant, patients with inclusive GGA or consolidation type tended to have
      a C-reactive protein level of >=1.0 mg/dL. CONCLUSION: If a patient with anemia
      and thrombocytopenia shows GGA or consolidation in the lung, pulmonary
      cryptococcosis should be given careful consideration.

PMID- 25767723
TI  - Phytochemical Analysis and Biological Activities of Cola nitida Bark.
AB  - Kola nut is chewed in many West African cultures and is used ceremonially. The
      aim of this study is to investigate some biological effects of Cola nitida's bark
      after phytochemical screening. The bark was collected, dried, and then powdered
      for the phytochemical screening and extractions. Ethanol and ethyl acetate
      extracts of C. nitida were used in this study. The antibacterial activity was
      tested on ten reference strains and 28 meat isolated Staphylococcus strains by
      disc diffusion method. The antifungal activity of three fungal strains was
      determined on the Potato-Dextrose Agar medium mixed with the appropriate extract.
      The antioxidant activity was determined by DPPH and ABTS methods. Our data
      revealed the presence of various potent phytochemicals. For the reference and
      meat isolated strains, the inhibitory diameter zone was from 17.5 +/- 0.7 mm (C.
      albicans) to 9.5 +/- 0.7 mm (P. vulgaris). The MIC ranged from 0.312 mg/mL to
      5.000 mg/mL and the MBC from 0.625 mg/mL to >20 mg/mL. The highest antifungal
      activity was observed with F. verticillioides and the lowest one with P.
      citrinum. The two extracts have an excellent reducing free radical activity. The
      killing effect of A. salina larvae was perceptible at 1.04 mg/mL. The purified
      extracts of Cola nitida's bark can be used to hold meat products and also like
      phytomedicine. 

PMID- 25767725
TI  - Intralipid therapy for inadvertent peripheral nervous system blockade resulting
      from local anesthetic overdose.
AB  - Although local anesthetics have an acceptable safety profile, significant
      morbidity and mortality have been associated with their use. Inadvertent
      intravascular injection of local anesthetics and/or the use of excessive doses
      have been the most frequent causes of local anesthetic systemic toxicity (LAST).
      Furthermore, excessive doses of local anesthetics injected locally into the
      tissues may lead to inadvertent peripheral nerve infiltration and blockade.
      Successful treatment of LAST with intralipid has been reported. We describe a
      case of local anesthetic overdose that resulted in LAST and in unintentional
      blockade of peripheral nerves of the lower extremity; both effects completely
      resolved with administration of intralipid. 

PMID- 25767724
TI  - Expression of p53 target genes in the early phase of long-term potentiation in
      the rat hippocampal CA1 area.
AB  - Gene expression plays an important role in the mechanisms of long-term
      potentiation (LTP), which is a widely accepted experimental model of synaptic
      plasticity. We have studied the expression of at least 50 genes that are
      transcriptionally regulated by p53, as well as other genes that are related to
      p53-dependent processes, in the early phase of LTP. Within 30 min after Schaffer
      collaterals (SC) tetanization, increases in the mRNA and protein levels of Bax,
      which are upregulated by p53, and a decrease in the mRNA and protein levels of
      Bcl2, which are downregulated by p53, were observed. The inhibition of Mdm2 by
      nutlin-3 increased the basal p53 protein level and rescued its tetanization
      induced depletion, which suggested the involvement of Mdm2 in the control over
      p53 during LTP. Furthermore, nutlin-3 caused an increase in the basal expression
      of Bax and a decrease in the basal expression of Bcl2, whereas tetanization
      induced changes in their expression were occluded. These results support the
      hypothesis that p53 may be involved in transcriptional regulation during the
      early phase of LTP. We hope that the presented data may aid in the understanding
      of the contribution of p53 and related genes in the processes that are associated
      with synaptic plasticity. 

PMID- 25767726
TI  - STEMI Associated with Overuse of Energy Drinks.
AB  - Coronary artery disease (CAD) and ST-elevation myocardial infarction (STEMI) are
      predominantly diseases of middle-aged and older adults and when found in younger
      adults are usually associated with a strong family history. However, this report
      details the case of a nonobese 26-year-old Hispanic male who presented with an
      acute STEMI despite having no family history or other apparent risk factors for
      CAD or STEMI beyond a two pack-year smoking history and excessive energy drink
      consumption. The patient reported consuming between eight and ten 473 mL cans per
      day. Cardiac catheterization subsequently confirmed total occlusion of his left
      circumflex coronary artery. 

PMID- 25767727
TI  - Periorbital edema secondary to positive airway pressure therapy.
AB  - Two patients developed bilateral, periorbital edema after initiating positive
      airway pressure (PAP) therapy with a full face mask. The periorbital edema was
      more pronounced in the morning and would dissipate throughout the day. This
      phenomenon seemed to be correlated with the direct pressure of the full face
      mask, which may have impaired lymphatic and venous drainage. To test this
      hypothesis, each patient was changed to a nasal pillow interface with subsequent
      improvement in the periorbital edema.

PMID- 25767728
TI  - Joint preservation of the wrist using articulated distraction arthroplasty: a
      case report of a novel technique.
AB  - Distraction arthroplasty of the ankle, elbow, and hip has become widely accepted
      and used within the orthopaedic community with excellent initial results which
      appear sustained. To date it has not been applied to the wrist in the same
      manner. A novel technique, drawn upon past success of articulated ankle
      distraction and static wrist distraction, was devised and evaluated by
      application of articulated wrist distraction performed over a 12-week period in a
      patient with poor functional outcome following limited wrist fusion.
      Posttreatment results showed improvement in range of motion (100-degree arc),
      subjective pain, and functional outcome measures (DASH 21.7, Mayo Wrist Score 80)
      comparable or better than either limited wrist fusion or proximal row carpectomy.
      Articulated wrist distraction initially appears to be a promising therapeutic
      option for the management of the stiff and painful wrist to maintain maximal
      function for which formal wrist arthrodesis may be the only alternative. 

PMID- 25767729
TI  - Osteoma presenting as a painless solitary mastoid swelling.
AB  - Introduction. Osteoma of the temporal bone is a very uncommon benign tumor of
      bone. Osteomas may occur in the external auditory canals but are reported to be
      very rare in the mastoid bone. Case Report. A 36-year-old male presented to our
      department with a hard swelling behind the right ear diagnosed as osteoma.
      Complete excision was done through a postauricular approach. Histopathology
      confirmed the diagnosis of osteoma. Conclusion. Osteomas, although rare, should
      be considered when dealing with any hard mastoid swelling. Complete removal can
      be ensured by drilling till the normal cortical bone is reached to avoid
      recurrence. A cortical mastoidectomy should be done if the mastoid air cell
      system is involved. 

PMID- 25767730
TI  - IgG4-Related Nasal Pseudotumor.
AB  - IgG4-related disease is recognized as one form of autoimmune pancreatitis. During
      the last ten years, it has also been described in several other organs. We
      present two patients with lesions showing a histological picture of fibrosis and
      lymphoplasmacytic infiltrations with abundant IgG4 positive plasma cells at
      hitherto unreported symmetrical nasal locations. The symmetrical complex
      consisted of one central lesion in the anterior nasal septum and the two others
      in each of the lateral nasal walls. The lesions extended from the anterior part
      of the inferior concha into the vestibulum and caused severe nasal obstruction. 

PMID- 25767731
TI  - Inverted lymphoglandular polyp in descending colon.
AB  - A 47-year-old male with a history of left colon cancer, status post left colon
      resection for 12 years, presented with rectal bleeding. Colonoscopic examination
      revealed an 8 mm sessile polyp in the proximal descending colon. Microscopic
      examination showed that the surface of this polyp was covered with a layer of
      normal colonic mucosa with focal surface erosion. In the submucosal layer, an
      intimate admixture of multiple cystically dilated glands and prominent lymphoid
      aggregates with germinal centers was seen. The glands were lined by columnar
      epithelium. Immunohistochemical staining showed the glands were positive for CK20
      and CDX2 and negative for CK7, with a low proliferative index, mostly consistent
      with reactive colonic glands. The patient remained asymptomatic after one-year
      follow-up. A review of the literature shows very rare descriptions of similar
      lesions, but none fits exactly this pattern. We would designate this inverted
      lymphoglandular polyp and present this case to raise the awareness of recognizing
      this unusual histological entity. 

PMID- 25767732
TI  - Early-onset neutropenia induced by rituximab in a patient with lupus nephritis
      and hemolytic anemia.
AB  - Rituximab is an anti-CD20 monoclonal antibody that has been used to treat several
      complications of systemic lupus erythematosus (SLE) including nephritis,
      cerebritis, and hematological disorders. Neutropenia is among the adverse events
      associated with rituximab; this usually occurs several weeks after therapy.
      However, early-onset neutropenia has been reported only in a few cases. Herein,
      we describe a 36-year-old Hispanic SLE woman who developed severe early-onset
      neutropenia (0.3 * 10(9)/L) after the second weekly rituximab infusion (375
      mg/m(2) weekly * 4) given for nephritis and hemolytic anemia. She also had early
      onset thrombocytopenia after rituximab therapy. Both hematological disorders
      resolved 12 days after the fourth and final dose. This case, together with few
      others, suggests that early-onset neutropenia may occur during rituximab therapy.
      Even though rituximab-induced neutropenia seems to be transient, it may
      predispose SLE patients to severe complications such as infections. 

PMID- 25767733
TI  - Elevated Troponin Serum Levels in Adult Onset Still's Disease.
AB  - Adult onset Still's disease (AOSD) is a rare inflammatory systemic disease that
      occasionally may affect myocardium. Diagnosis is based on typical AOSD symptoms
      after the exclusion of well-known infectious, neoplastic, or
      autoimmune/autoinflammatory disorders. In the case of abrupt, recent onset AOSD,
      it could be particularly difficult to make the differential diagnosis and in
      particular to early detect the possible heart involvement. This latter event is
      suggested by the clinical history of the four patients described here,
      incidentally observed at our emergency room. All cases were referred because of
      acute illness (high fever, malaise, polyarthralgias, skin rash, and sore throat),
      successively classified as AOSD, and they presented abnormally high levels of
      serum troponin without overt symptoms of cardiac involvement. The timely
      treatment with steroids (3 cases) or ibuprofen (1 case) leads to the remission of
      clinicoserological manifestations within few weeks. These observations suggest
      that early myocardial injury might be underestimated or entirely overlooked in
      patients with AOSD; routine cardiac assessment including troponin evaluation
      should be mandatory in all patients with suspected AOSD. 

PMID- 25767734
TI  - Inflammatory myofibroblastic tumor of the breast.
AB  - Inflammatory myofibroblastic tumors (IMTs) of the breast represent extremely rare
      lesions. Due to the scarcity of reports, their natural history, recurrence, and
      metastatic potential remain poorly defined. We report on a case of a primary
      breast IMT in a postmenopausal female patient treated successfully with breast
      conserving surgery and review the literature pertaining to this rare entity. 

PMID- 25767735
TI  - First reported case of isolated persistent genital arousal disorder in a male.
AB  - Introduction. Persistent genital arousal disorder (PGAD) is a newly recognized
      disorder in women. It is described as unwanted, persistent feelings of genital
      arousal unrelated to sexual desire and not relieved by orgasm. Its prevalence is
      estimated to approach 1% of young women. Until now, this has not been described
      in men. Aim. Here we present a case of a 27-year-old male with symptoms
      consistent with PGAD and describe successful treatment. Methods. A 27-year-old
      male presented to urology clinic with the chief complain of persistent feelings
      of impending orgasm. He reported a sensation similar, but not identical, to
      sexual arousal that did not occur in the setting of sexual thoughts or desire.
      Orgasm alleviated the arousal for only a short time after which the symptoms
      would return. This had become quite bothersome to him. Results. After assessing
      for a neurological cause and finding none, the patient was started on paroxetine
      daily with complete resolution of symptoms. Conclusions. PGAD is a disorder
      previously described only in females. Although symptoms of PGAD have been
      described in a male as part of another disorder complex, this report describes
      the first reported isolated case in a male and the successful treatment. 

PMID- 25767736
TI  - Patient related factors affecting adherence to antimalarial medication in an
      urban estate in ghana.
AB  - Our aim was to measure the adherence to Artemisinin based Combination Therapy and
      to determine patient related factors that affect adherence. Three hundred (300)
      patients receiving ACT treatment dispensed from the community pharmacy were
      randomly selected and followed up on the fourth day after the start of their
      three-day therapy to assess adherence. Adherence was measured by pill count.
      Quantitative interviews using a semistructured questionnaire were used to assess
      patients' knowledge and beliefs on malaria and its treatment. Adherence levels to
      the ACTs were 57.3%. Patient related factors that affected adherence to ACTs were
      patients' knowledge on the dosage (P = 0.007; v = 0.457), efficacy (P = 0.009; v
      = 0.377), and side effects (P = 0.000; v = 0.403) of the ACTs used for the
      management of malaria, patients' awareness of the consequences of not completing
      the doses of antimalarial dispensed (P = 0.001; v = 0.309), and patients' belief
      that "natural remedies are safer than medicines" and "prescribers place too much
      trust in medicines." There was no significant relationship between adherence and
      patients' knowledge on the causes, signs, and symptoms of malaria. There is the
      need for pharmacy staff to stress on these variables when counseling patients on
      antimalarials as these affect adherence levels. 

PMID- 25767737
TI  - Salivary acetylcholinesterase activity is increased in Parkinson's disease: a
      potential marker of parasympathetic dysfunction.
AB  - Introduction. Decreased salivary flow and xerostomia are frequent findings in
      Parkinson's disease (PD), possibly caused by alterations in the parasympathetic
      tonus. Here we explore salivary acetylcholinesterase (AChE) activity as a
      potential biomarker in PD. Methods. We measured salivary flow, AChE activity, and
      total protein concentration in 30 PD patients and 49 healthy controls. We also
      performed exploratory correlation analyses with disease duration, motor symptom
      severity, autonomic complaints, and other nonmotor symptoms. Results. PD patients
      displayed significantly decreased salivary flow rate, significantly increased
      salivary AChE activity, and total protein concentration. Importantly, the AChE
      activity/total protein ratio was significantly increased in PD patients,
      suggesting that increased AChE activity cannot be explained solely by
      upconcentration of saliva. The Unified PD Rating Scale (UPDRS) score displayed
      significant correlation with total salivary protein (P = 0.002) and near
      significant correlation with salivary flow (P = 0.07). Color vision test scores
      were also significantly correlated with AChE activity (P = 0.04) and total
      protein levels (P = 0.002). Conclusion. Salivary AChE activity is increased in PD
      patients compared to healthy controls. Future studies are needed to elucidate
      whether this parameter reflects the extent of neuronal damage and parasympathetic
      denervation in the salivary glands of PD patients. 

PMID- 25767738
TI  - Statistical Methods for the Investigation of Solvolysis Mechanisms Illustrated by
      the Chlorides of the Carbomethoxy Protecting Groups NVOC and FMOC.
AB  - The solvolysis of 4,5-dimethoxy-2-nitrobenzyl chloroformate (NVOC-Cl, 1) is
      followed at 25.0 degrees C in twenty hydroxylic solvents. A comparison with
      previously published rates for benzyl chloroformate and p-nitrobenzyl
      chloroformate indicates that the inductive effect of the nitro and the two
      methoxy groups strongly influences the rate of reaction. For 1, the specific
      rates of solvolysis are correlated using an extended Grunwald-Winstein (G-W)
      treatment. A direct comparison with the data for phenyl chloroformate (PhOCOCl)
      in identical solvents strongly suggests that the addition step within an addition
      elimination mechanism is rate-determining for both substrates. A reevaluation of
      the kinetic data for 9-fluorenylmethyl chloroformate (FMOC-Cl, 2) involves a
      correlation of log?(k/k o )2 versus log?(k/k o )PhOCOCl. In this plot, deviations
      were observed in solvents rich in a hydrogen-bonding fluoroalcohol component.
      Omitting the aqueous fluoroalcohol rate measurements for 2 in an analysis using
      the extended G-W equation suggested the occurrence of dual pathways differing in
      the dependences upon the ionizing power and nucleophilicity of the solvent. In
      addition, the fluorenyl ring is rotated out of the plane containing the ether
      oxygen and, as a result, PhOCOCl is found to solvolyze 20 times faster than 2 in
      ethanol and methanol. 

PMID- 25767739
TI  - Application of Design of Experiment and Simulation Methods to Liquid
      Chromatography Analysis of Topical HIV Microbicides Stampidine and HI443.
AB  - This study intended to determine if experimental design and Monte Carlo
      simulation methods can be utilized to optimize the liquid chromatography (LC)
      analysis of active molecules. The method was applied for the simultaneous
      analysis of two topical microbicides, stampidine (STP) and HI443 in bulk and
      nanoformulations. The Plackett-Burman design was used for screening; whereas, Box
      Behnken design was used to evaluate the main and interaction effects of the
      selected factors on the responses, namely peak area of STP (Y1), HI443 (Y2),
      tailing of STP (Y3), and HI443 (Y4). The Monte Carlo simulation was applied to
      get the minimum defect rate (DR) of the process. The optimized LC conditions were
      found to be X1; flow rate: 0.6 mL/min, X2; injection volume: 18 MUL, and X3;
      initial gradient acetonitrile ratio: 92% v/v with a minimal DR of 0.077%. The
      optimized method was applied to determine the percent encapsulation efficiency
      (%EE) and in vitro release profile of STP and HI443 from solid lipid
      nanoparticles (SLNs). The %EE of STP and HI443 in SLNs was found to be 30.56 +/-
      9.44 and 94.80 +/- 21.90% w/w, respectively, (n=3). It was observed that the
      release kinetics of STP followed the first order, whereas, HI443 followed the
      Peppas kinetic model in SLNs. The LC method was also applied for the estimation
      of molar extinction coefficients (epsilon270 ) of both drugs for the first time.
      These values were estimated to be 7,569.03 +/- 217.96 and 17,823.67 +/- 88.12
      L/mol/cm for STP and HI443, respectively, (n=3). The results suggest that
      experimental design and Monte Carlo simulation can be effectively used to reduce
      the DR of a process and to optimize the chromatographic conditions for the
      analysis of bio-active agents as applied in this study.

PMID- 25767740
TI  - Disability, Health Insurance and Psychological Distress among US Adults: An
      Application of the Stress Process.
AB  - Structural resources, including access to health insurance, are understudied in
      relation to the stress process. Disability increases the likelihood of mental
      health problems, but health insurance may moderate this relationship. We explore
      health insurance coverage as a moderator of the relationship between disability
      and psychological distress. A pooled sample from 2008-2010 (N=57,958) was
      obtained from the Integrated Health Interview Series. Chow tests were performed
      to assess insurance group differences in the association between disability and
      distress. Results indicated higher levels of distress associated with disability
      among uninsured adults compared to their peers with public or private insurance.
      The strength of the relationship between disability and distress was weaker for
      persons with public compared to private insurance. As the Affordable Care Act is
      implemented, decision-makers should be aware of the potential for insurance
      coverage, especially public, to ameliorate secondary conditions such as
      psychological distress among persons who report a physical disability.

PMID- 25767742
TI  - Long-term survival in a patient with progressive multifocal leukoencephalopathy
      after therapy with rituximab, fludarabine and cyclophosphamide for chronic
      lymphocytic leukemia.
AB  - A 50-year-old male with chronic lymphocytic leukemia (CLL) was treated with
      fludarabine, cyclophosphamide and rituximab, which produced a complete remission.
      Eight months after the last dose of rituximab he had visual disturbance,
      diminished muscular strength in the right arm and vesicular-papular lesions in
      the left ophthalmic branch region of the V cranial nerve. These were initially
      interpreted as herpes virus encephalopathy (HVE), but brain magnetic resonance
      imaging (MRI) showed evidence of demyelination consistent with progressive
      multifocal leukoencephalopathy (PML). Cerebrospinal fluid (CSF) analysis was
      negative for varicella zoster virus (VZV) and John Cunningham virus (JCV) DNA.
      The clinical suggestion of PML prompted us to perform a brain biopsy and to start
      treatment with mefloquine. In the brain biopsy, histopathological features of
      demyelination were described and the polymerase chain reaction (PCR) identified
      JCV, confirming the diagnosis of PML. Treatment with mefloquine (250 mg/week) and
      dexamethasone (4 mg/day) was started and maintained for 6 months. A year later
      there was an almost complete resolution of the MRI lesions and the patient
      achieved a stable clinical state with persisting motor impairment and severe
      epilepsy. The patient is alive 38 months after diagnosis of PML, which is the
      longest known survival to date. 

PMID- 25767741
TI  - Interaction with the effector dynamin-related protein 1 (Drp1) is an ancient
      function of Rab32 subfamily proteins.
AB  - The mitochondria-associated membrane (MAM) is an endoplasmic reticulum (ER)
      domain that forms contacts with mitochondria and accommodates Ca2+ transfer
      between the two organelles. The GTPase Rab32 regulates this function of the MAM
      via determining the localization of the Ca2+ regulatory transmembrane protein
      calnexin to the MAM. Another function of the MAM is the regulation of
      mitochondrial dynamics mediated by GTPases such as dynamin-related protein 1
      (Drp1). Consistent with the importance of the MAM for mitochondrial dynamics and
      the role of Rab32 in MAM enrichment, the inactivation of Rab32 leads to
      mitochondrial collapse around the nucleus. However, Rab32 and related Rabs also
      perform intracellular functions at locations other than the MAM including
      melanosomal trafficking, autophagosome formation and maturation, and retrograde
      trafficking to the trans-Golgi network (TGN). This plethora of functions raises
      questions concerning the original cellular role of Rab32 in the last common
      ancestor of animals and its possible role in the last eukaryotic common ancestor
      (LECA). Our results now shed light on this conundrum and identify a role in Drp1
      mediated mitochondrial dynamics as one common denominator of this group of Rabs,
      which includes the paralogues Rab32A and Rab32B, as well as the more recently
      derived Rab29 and Rab38 proteins. Moreover, we provide evidence that this
      mitochondrial function is dictated by the extent of ER-association of Rab32
      family proteins.

PMID- 25767743
TI  - Free Care Is Not Enough: Barriers to Attending Free Clinic Visits in a Sample of
      Uninsured Individuals with Diabetes.
AB  - Free care does not always lead to improved outcomes. Attendance at free clinic
      appointments is unpredictable. Understanding barriers to care could identify
      innovative interventions. The purpose of this study was to examine patient
      characteristics, biophysical outcomes, and health care utilization in uninsured
      persons with diabetes at a free clinic. A sample of 3139 patients with at least
      one chronic condition was identified and comparisons were made between two
      groups: those who attended all scheduled appointments and those who did not.
      Geographic distance to clinic and multiple chronic conditions were identified as
      barriers to attendance. After one year, missing more than one visit had a
      positive correlation with increased weight, A1C, and lipids. Additionally,
      patients who missed visits had higher blood pressure, depression scores, and
      numbers of medications. Future research should further enhance understanding of
      barriers to care, build knowledge of how social and behavioral determinants
      contribute to negative outcomes in the context of rurality. Innovative methods to
      deliver more frequent and intensive interventions will not be successful if they
      are not accessible to patients.

PMID- 25767745
TI  - A Pilot Study on Feasibility and Effectiveness of Intraoperative Spectral-Domain
      Optical Coherence Tomography in Glaucoma Procedures.
AB  - PURPOSE: To demonstrate the use of a spectral-domain optical coherence tomography
      (SDOCT) integrated surgical microscope in glaucoma surgery. METHODS: An SDOCT
      system was used to interface directly with an ophthalmic surgical microscope, to
      allow real-time intraoperative SDOCT (iOCT) imaging during glaucoma procedures
      like phaco-trabeculectomy, Ahmed glaucoma valve (AGV) implantation, gonio
      synechiolysis, and bleb needling. The various surgical steps during glaucoma
      surgeries where iOCT can be of potential help in guiding the surgeon were
      recorded. RESULTS: High-resolution, cross-sectional images of the relevant
      structures were achieved with the iOCT system in all procedures. The surgeon
      could determine the depth of the scleral dissection, the intrastomal bed, the
      path of the AGV tube in the eye, the release of peripheral anterior synechiae and
      the efficacy of needling with respect to breakage of loculations; most of these
      are technically 'blind' procedures, where the outcomes are determined
      postoperatively. Metallic instruments cast a shadow on tissues below, thereby
      restricting the use of the device in its current state. CONCLUSIONS: The iOCT
      system provided high quality, intraoperative, real-time imaging, which could
      possibly improve the safety and efficacy of the surgical procedures in glaucoma.
      Further studies and modifications to the iOCT are required to better understand
      and increase the uptake of this technology in daily practice. TRANSLATIONAL
      RELEVANCE: The iOCT, with further advancements in its technology, could
      potentially provide the surgeon both quantitative and qualitative, real-time
      depth and tissue proximity details, thus improving the safety and accuracy of
      glaucoma surgery.

PMID- 25767744
TI  - Why Do People (Still) Go Blind from Glaucoma?

PMID- 25767746
TI  - Central Executive Dysfunction and Deferred Prefrontal Processing in Veterans with
      Gulf War Illness.
AB  - Gulf War Illness is associated with toxic exposure to cholinergic disruptive
      chemicals. The cholinergic system has been shown to mediate the central executive
      of working memory (WM). The current work proposes that impairment of the
      cholinergic system in Gulf War Illness patients (GWIPs) leads to behavioral and
      neural deficits of the central executive of WM. A large sample of GWIPs and
      matched controls (MCs) underwent functional magnetic resonance imaging during a
      varied-load working memory task. Compared to MCs, GWIPs showed a greater decline
      in performance as WM-demand increased. Functional imaging suggested that GWIPs
      evinced separate processing strategies, deferring prefrontal cortex activity from
      encoding to retrieval for high demand conditions. Greater activity during high
      demand encoding predicted greater WM performance. Behavioral data suggest that WM
      executive strategies are impaired in GWIPs. Functional data further support this
      hypothesis and suggest that GWIPs utilize less effective strategies during high
      demand WM.

PMID- 25767747
TI  - Controlled protein delivery in the generation of microvascular networks.
AB  - Rapid induction and stabilization of new microvascular networks is essential for
      the proper functioning of engineered tissues. Many efforts to achieve this goal
      have used proangiogenic proteins-such as vascular endothelial growth factors-to
      induce the formation of new microvessels. These proteins have demonstrated
      promise in improving vascularization, but it is also clear that the spatial and
      temporal presentation of these signals is important for achieving proper vascular
      function. Delivery systems that present proteins in a localized and sustained
      manner, can promote the formation and stabilization of microvascular networks by
      precisely presenting proangiogenic proteins at desired locations, and for
      specified durations. Further, these systems allow for some control over the
      sequence of release of multiple proteins, and it has become clear that such
      coordination is critical for the development of fully functional and mature
      vascular structures. This review focuses on the actions of proangiogenic proteins
      and the innovations in controlled release technologies that precisely deliver
      these to stimulate microvascular network formation and stabilization. 

PMID- 25767749
TI  - Do provider attitudes about electronic health records predict future  electronic
      health record use?
AB  - INTRODUCTION: Prior research has shown that provider attitudes about EHRs are
      associated with successful adoption. There is no evidence on whether comfort with
      technology and more positive attitudes about EHRs affect use of EHR functions
      once they are adopted. METHODS: We used data from a survey of providers in the
      Primary Care Information Project, a bureau of the New York City Department of
      Health and Mental Hygiene and measures of use from their EHRs. The main predictor
      variables were scores on three indices: comfort with computers, positive
      attitudes about EHRs, and negative attitudes about EHRs. The main outcome
      measures were four measures of use of EHR functions. We used linear regression
      models to test the association between the three indices and measures of EHR use.
      RESULTS: The mean comfort with computers score was 2.37 (SD0.53) on a scale of 1
      3 with 3 being the most comfortable. The mean positive attitude score was 2.74
      (SD 0.40) on a scale of 1-3 with 3 being more positive. The mean negative
      attitude score was 1.81 (SD 0.54) on a scale of 1-3 with 3 being more negative.
      Within the first twelve months of having the EHR, 59.5% of visits had allergy
      information entered into a structured field, 64.8% had medications reviewed, and
      74.3% had blood pressured entered. Among visits with a prescription generated,
      24.5% had prescriptions electronically. In multivariate regression analysis, we
      found no significant correlations between comfort with computers, positive
      attitudes about EHRs, or negative attitudes about EHRs and any of the measures of
      use. DISCUSSION: Comfort with computers and attitudes about EHRs did not predict
      future use of the EHR functions. Our findings suggest that meaningful use of the
      EHR may not be affected by providers' prior attitudes about EHRs.

PMID- 25767750
TI  - Assessing and improving data quality from community health workers: a successful
      intervention in Neno, Malawi.
AB  - SETTING: A community health worker (CHW) program was established in Neno
      District, Malawi, in 2007 by Partners In Health in support of Ministry of Health
      activities. Routinely generated CHW data provide critical information for program
      monitoring and evaluation. Informal assessments of the CHW reports indicated poor
      quality, limiting the usefulness of the data. OBJECTIVES: 1) To establish the
      quality of aggregated measures contained in CHW reports; 2) to develop
      interventions to address poor data quality; and 3) to evaluate changes in data
      quality following the intervention. DESIGN: We developed a lot quality assurance
      sampling-based data quality assessment tool to identify sites with high or low
      reporting quality. Following the first assessment, we identified challenges and
      best practices and followed the interventions with two subsequent assessments.
      RESULTS: At baseline, four of five areas were classified as low data quality.
      After 8 months, all five areas had achieved high data quality, and the reports
      generated from our electronic database became consistent and plausible.
      CONCLUSION: Program changes included improving the usability of the reporting
      forms, shifting aggregation responsibility to designated assistants and providing
      aggregation support tools. Local quality assessments and targeted interventions
      resulted in immediate improvements in data quality.

PMID- 25767751
TI  - Antioxidant activity and total phenolic content of Boerhavia elegans (choisy)
      grown in Baluchestan, Iran.
AB  - OBJECTIVE: Boerhaavia elegans L. (Nyctaginaceae) is a medicinal plant used for
      the treatment of kidney disorders, urinary tract disorders and blood purification
      in Baluch tribe. The aim of present study is to evaluate the antioxidant property
      of B. elegans species for the first time. MATERIALS AND METHODS: Different parts
      (leaf, stem and fruit) of the plant were extracted by using various solvents
      (water, methanol, chloroform and ethyl acetate) and evaluated for their
      antioxidant activity using DPPH (2, 2-diphenyl-1 picryl hydrazyl) and FRAP
      (ferric reducing antioxidant power) methods. In addition, total phenolic content
      was determined by Folin-Ciocalteu reagent. RESULTS: Antioxidant results were
      expressed as IC50. The antioxidant power in DPPH and FRAP assay were evaluated as
      shown in decreasing order: Methanolic extract > Aqueous extract > Ethyl acetate
      extract > Chloroform extract, for all parts of the plant. In both methods of
      antioxidant assay and Folin-Ciocalteu method, methanolic extract of leaf
      exhibited the highest activity and the most phenolic content IC50= 6.85 ppm and
      16.41 mg GA/g d w respectively. Total phenolic content had a positive
      relationship with antioxidant capacity in extracts and there was a high
      correlation (r=1.00, p<0.01) between antioxidant activities as determined by both
      antioxidant assays for various parts. CONCLUSION: The results of the experiments
      showed that B. elegans extract had significant antioxidant effects. This high
      antioxidant activity may be linked to phenolic contents of the plant but
      complementary investigations are suggested in order to determine active elements.

PMID- 25767748
TI  - Impact of Cannabis Use on the Development of Psychotic Disorders.
AB  - The link between cannabis use and psychosis comprises three distinct
      relationships: acute psychosis associated with cannabis intoxication, acute
      psychosis that lasts beyond the period of acute intoxication, and persistent
      psychosis not time-locked to exposure. Experimental studies reveal that cannabis,
      tetrahydrocannabinol (THC) and synthetic cannabinoids reliably produce transient
      positive, negative, and cognitive symptoms in healthy volunteers. Case-studies
      indicate that cannabinoids can induce acute psychosis which lasts beyond the
      period of acute intoxication but resolves within a month. Exposure to cannabis in
      adolescence is associated with a risk for later psychotic disorder in adulthood;
      this association is consistent, temporally related, shows a dose-response, and is
      biologically plausible. However, cannabis is neither necessary nor sufficient to
      cause a persistent psychotic disorder. More likely it is a component cause that
      interacts with other factors to result in psychosis. The link between cannabis
      and psychosis is moderated by age at onset of cannabis use, childhood abuse and
      genetic vulnerability. While more research is needed to better characterize the
      relationship between cannabinoid use and the onset and persistence of psychosis,
      clinicians should be mindful of the potential risk of psychosis especially in
      vulnerable populations, including adolescents and those with a psychosis
      diathesis.

PMID- 25767752
TI  - Neuroprotective, antimicrobial, antioxidant, chemotherapeutic, and antidiabetic
      properties of Salvia Reuterana: A mini review.
AB  - OBJECTIVES: Herbal medicine is known as a valid alternative treatment. Salvia
      Reuterana, which has been used in the Iranian traditional medicine, is mostly
      distributed in the central highlands of Iran. Salvia Reuterana is a medicinal
      herb with various therapeutic usages. The aim of the present review is to take
      account of pharmacological properties of Salvia Reuterana. MATERIALS AND METHODS:
      The present review summarizes the literature with respect to various
      pharmacological properties of Salvia Reuterana. RESULTS: Salvia Reuterana
      possesses neurological, antimicrobial, antioxidant, chemotherapeutic, and
      antidiabetic properties. CONCLUSIONS: Salvia Reuterana can be used as an
      alternative for treatment of several disorders.

PMID- 25767753
TI  - Renal effects of Anchomanes difformis crude extract in wistar rats.
AB  - OBJECTIVE: Anchomanes difformis is a member of the plant family Araceae which is
      used as a diuretic but also has other medicinal applications. This study
      investigates the dietary effects of A. difformis on the kidneys of adult wistar
      rats. MATERIALS AND METHODS: Sixteen rats were used and were weighed, before and
      after the experiment. All rats were randomly divided into four groups. All groups
      were treated with the following regimen for two weeks. The control group (A) was
      fed on feed mash and water ad libitum throughout the period. The treatment groups
      B, C, and D received feed mash mixed with crude extract of A. difformis in the
      following proportions: 25:75(g), 50:50(g), and 75:25(g), respectively. The
      kidneys of the experimental animals were histologically examined for morphologic
      changes. RESULTS: RESULTS showed a significant difference (p<0.05) in the kidney
      weight of the treatment groups compared with the control. Histological
      examination of the renal tissues also showed considerable lesions such as
      inflammation, focal cortical and interstitial hemorrhage, and fibrosis in the
      treated rats compared with the control. CONCLUSION: The current study results
      suggest renal toxicity with excessive consumption of A.difformis.

PMID- 25767754
TI  - Effect of five year storage on total phenolic content and antioxidant capacity of
      almond (Amygdalus communisL.) hull and shell from different genotypes.
AB  - OBJECTIVES: Almond (Prunus amygdalus) hull and shell are agricultural by-products
      that are a source of phenolic compounds.The processing of almond produce shell
      and hull, accounts for more than 50% by dry weight of the almond fruits.
      Recently, more studies have focused on the influence of storage conditions and
      postharvest handling on the nutritional quality of fruits, especially the
      antioxidant phenolics. In this study, influence of long-term storage (five years)
      on the total phenolic and antioxidant capacity of almond hull and shell from
      different genotypes was evaluated. MATERIALS AND METHODS: The fruits of subjected
      genotypes were collected and their hull and shell were separated. They were dried
      and reduced to fine powder. This powder stored at room temperature for five
      years. The total phenolic content (TPC) and bioactivities (antioxidant potential:
      DPPH and ABTS radical scavenging and reducing power) of extracts were evaluated
      using spectrophotometric methods. RESULTS: It was found that TPC content and
      bioactivity levels in the stored almond hull and shell were different, compared
      to the hulls and shells which were evaluated in 2007. S1-4 genotype had the
      highest TPC and reducing power in its hull and shell.Low correlation coefficient
      was observed between phenolic content and the DPPH radical scavenging percentage
      in hull and shell extract. CONCLUSIONS: For the first time, results of this
      investigation showed that storage can influence the antioxidant and antiradical
      potential of almond hull and shell.

PMID- 25767755
TI  - Efficacy of Cuminum cyminum essential oil on FUM1 gene expression of fumonisin
      producing Fusarium verticillioides strains.
AB  - OBJECTIVES: The purpose of this study was to evaluate the effect of Cuminum
      cyminum (C. cyminum) essential oil on the growth and FUM1 gene expression of
      fumonisin-producing Fusarium verticillioides (F. verticillioides) strains
      isolated from maize. MATERIALS AND METHODS: All fungal strains were cultured on
      potato dextrose agar (PDA) slopes at 30 degrees C for 7 days. The antifungal
      activity was evaluated by broth microdilution assay. One set of primers was F.
      verticillioides species specific, which selectively amplified the intergenic
      space region of rDNA. The other set of primers was specific to FUM1 gene region
      of fumonisin-producing F. verticillioides. FUM1 transcript levels were quantified
      using a reverse transcription-polymerase chain reaction (RT-PCR) protocol.
      RESULTS: Minimum inhibitory concentration (MIC) values of C. cyminum oil against
      F. verticillioides strains varied from 0.195 to 0.781 ul.ml(-1) (mean MIC value:
      0.461 ul.ml(-1)) indicating 54.5% of the fungal strains inhibited at 0.390 ul.ml(
      1). PCR analysis of FUM1 gene expression revealed that DNA fragment of 183 bp was
      amplified in all the isolates of F. verticillioides before treatment with C.
      cyminum essential oil. Based on RT-PCR analyses, reduction in the expression of
      fumonisin biosynthetic genes was significant only for FUM1 gene (p<0.05), while
      no effect was observed on ITS gene. CONCLUSIONS: This study showed that all F.
      verticillioides isolates were susceptible to C. cyminum essential oil, indicating
      a significant reduction in the growth of fungal isolates. In addition, this oil
      completely inhibited the expression of FUM1 gene in concentrations dose
      dependently.

PMID- 25767756
TI  - Pomegranate seed hydroalcoholic extract improves memory deficits in
      ovariectomized rats with permanent cerebral hypoperfusion /ischemia.
AB  - OBJECTIVES: Estrogen deficit following menopause results in cognitive behaviors
      impairment. This study aimed to evaluate the effects of pomegranate seed extract
      (PGSE) on avoidance memories after permanent bilateral common carotid arteries
      occlusion (2CCAO) in ovariectomized (OVX) rats. MATERIALS AND METHODS: Adult
      female Wistar rats were divided randomly into eight groups with 8 rats in each
      group: 1) Sham-operated for ovaries and 2CCAO (ShO); 2) OVX and sham operated for
      ischemia (OShI); 3-7) OVX with 2CCAO (OI) received PGSE (100, 200, 400 and 800
      mg/2ml/kg or normal saline, orally) for 14 days (OI+E100, 200, 400, 800 or
      OI+Veh); 8) OShI received most effective dose of PGSE (200 and 400 mg/kg for
      passive and active avoidance memories respectively). Active and passive avoidance
      tasks were measured in Y-maze and two-way shuttle box respectively. Data were
      analyzed with one-way and RM-ANOVA followed by HSD post-hoc test. RESULTS:
      Sensorimotor impaired in OShI+Veh and OI+Veh (P<0.001 vs. ShO). PGSE improved it
      significantly in dose dependently manner (P<0.001 vs. OI+Veh). Both types of
      memories were significantly impaired in OVX rats before and after 2CCAO
      (P<0.001). PGSE treatment significantly improved memories in OI groups (P<0.05,
      P<0.01 and P<0.001) compared with OI+Veh. No toxicity was observed with PGSE
      consumption (800 mg/kg, 2 weeks, orally). CONCLUSION: PGSE exhibits therapeutic
      potential for avoidance memories, which is most likely related at least in part
      to its phytoestrogenic and also antioxidative actions.

PMID- 25767757
TI  - Antibacterial and antifungal activities of the endemic species Glaucium
      vitellinum Boiss. and Buhse.
AB  - OBJECTIVES: Belonging to Papaveraceae family, Glaucium vitellinum is one of the
      Persian endemic plants which has not been investigated biologically. The present
      paper focused on the assessment of the antibacterial and antifungal activities of
      the total methanol extract and alkaloid sub-fraction of the flowering aerial
      parts of G. vitellinum. MATERIALS AND METHODS: The antibacterial and antifungal
      activities were investigated using cup plate method and disc diffusion assay,
      respectively. The MIC values of the active samples were determined using micro
      plate dilution method. RESULTS: The crude extract and alkaloid sub-fraction of G.
      vitellinum had significant inhibition activity on the growth of S. aureus and S.
      typhi. From antifungal assay, it is concluded that only the yeast C. albicans,
      showed a high sensitivity to the extract and especially to the related alkaloid
      sub-fraction. CONCLUSIONS: Regarding the results, G. vitellinum could be employed
      as a natural antibacterial and antifungal agent against S. aureus, S. typhi, and
      C. albicans, respectively. Moreover, based on the results of this study, further
      in vivo and ex vivo confirmatory tests for total methanol extract and alkaloid
      sub-fraction are recommended.

PMID- 25767758
TI  - Immunomudulatory effects of hydroalcoholic extract of Hypericum perforatum.
AB  - OBJECTIVE: Hypericum perforatum (St. John's Wort) has long been used in
      traditional medicine to treat a variety of internal and external ailments. The
      present study was done to evaluate the immumodulatory potentials of the
      hydroalcoholic extract of H. perforatum. MATERIALS AND METHODS: Twenty male
      BALB/c-mice were randomly allocated in two equal groups and immunized with sheep
      red blood cells (SRBCs) and complete Freund's adjuvant. Mice in the treatment
      group orally received hydroalcoholic extract of H. perforatum (110 mg/Kg daily)
      from the beginning of the study which continued for 2 weeks. RESULTS: The data
      indicated a significant increase in the level of anti-SRBC antibody and
      simultaneously a significant decrease in the level of cellular immunity, an
      enhancement in foot pad thickness, in treatment group compared to control group.
      The level of the respiratory burst in phagocytic cells and the level of
      lymphocyte proliferation in splenocytes were significantly decreased in the
      treatment group compared to control group. Moreover, extract caused a significant
      reduction in the production of pro-inflammatory IL-17 as well as IFN-gamma,
      parallel to increasing the level of IL-6. CONCLUSIONS: The hydroalcoholic extract
      of H. perforatum may be used as a natural source for treatment of
      immunopathologic conditions.

PMID- 25767759
TI  - Anti-inflammatory, Analgesic and Antiulcer properties of Porphyra vietnamensis.
AB  - OBJECTIVES: Aim of the present work was to investigate the anti-inflammatory,
      analgesic and antiulcer effects of red seaweed Porphyra vietnamensis (P.
      vietnamenis). MATERIALS AND METHODS: Aqueous (POR) and alcoholic (PE) fractions
      were successfully isolated from P. vietnamenis. Further biological investigations
      were performed using a classic test of paw edema induced by carrageenan, writhing
      induced by acetic acid, hot plate method and naproxen induced gastro-duodenal
      ulcer. RESULTS: Among the fractions POR showed better activity. POR and PE
      significantly (p < 0.05) reduced carrageenan induced paw edema in a dose
      dependent manner. In the writhing test POR significantly (p < 0.05) reduced
      abdominal writhes than PE. In hot plate method POR showed better analgesic
      activity than PE. POR showed comparable ulcers reducing potential (p<0.01) to
      that of omeprazole, and has more ulcer reducing potential then PE. CONCLUSIONS:
      The results of this study demonstrated that P. vietnamenis aqueous fraction
      possesses biological activity that is close to the standards taken for the
      treatment of peripheral painful or/and inflammatory and ulcer conditions.

PMID- 25767761
TI  - Reforming craniofacial orthodontics via stem cells.
AB  - Stem cells are the most interesting cells in cell biology. They have the
      potential to evolve as one of the most powerful technologies in the future. The
      future refers to an age where it will be used extensively in various fields of
      medical and dental sciences. Researchers have discovered a number of sources from
      which stem cells can be derived. Craniofacial problems are very common and occur
      at all ages. Stem cells can be used therapeutically in almost every field of
      health science. In fact, many procedures will be reformed after stem cells come
      into play. This article is an insight into the review of the current researches
      being carried out on stem cells and its use in the field of orthodontics, which
      is a specialized branch of dentistry. Although the future is uncertain, there is
      a great possibility that stem cells will be used extensively in almost all major
      procedures of orthodontics. 

PMID- 25767760
TI  - Biofilm in endodontics: A review.
AB  - Endodontic disease is a biofilm-mediated infection, and primary aim in the
      management of endodontic disease is the elimination of bacterial biofilm from the
      root canal system. The most common endodontic infection is caused by the surface
      associated growth of microorganisms. It is important to apply the biofilm concept
      to endodontic microbiology to understand the pathogenic potential of the root
      canal microbiota as well as to form the basis for new approaches for
      disinfection. It is foremost to understand how the biofilm formed by root canal
      bacteria resists endodontic treatment measures. Bacterial etiology has been
      confirmed for common oral diseases such as caries and periodontal and endodontic
      infections. Bacteria causing these diseases are organized in biofilm structures,
      which are complex microbial communities composed of a great variety of bacteria
      with different ecological requirements and pathogenic potential. The biofilm
      community not only gives bacteria effective protection against the host's defense
      system but also makes them more resistant to a variety of disinfecting agents
      used as oral hygiene products or in the treatment of infections. Successful
      treatment of these diseases depends on biofilm removal as well as effective
      killing of biofilm bacteria. So, the fundamental to maintain oral health and
      prevent dental caries, gingivitis, and periodontitis is to control the oral
      biofilms. From these aspects, the formation of biofilms carries particular
      clinical significance because not only host defense mechanisms but also
      therapeutic efforts including chemical and mechanical antimicrobial treatment
      measures have the most difficult task of dealing with organisms that are gathered
      in a biofilm. The aim of this article was to review the mechanisms of biofilms'
      formation, their roles in pulpal and periapical pathosis, the different types of
      biofilms, the factors influencing biofilm formation, the mechanisms of their
      antimicrobial resistance, techniques to identify biofilms. 

PMID- 25767762
TI  - A comprehensive comparative analysis of articles retracted in 2012 and 2013 from
      the scholarly literature.
AB  - BACKGROUND: Science is a dynamic subject with ever-changing concepts and is said
      to be self-correcting. One of the major mechanisms of self-correction is
      retraction of flawed work. AIM: To study the various parameters associated with
      retraction of scientific articles in 2012 and 2013 and discuss the current trends
      in article retraction over the period of 2 years. MATERIALS AND METHODS: Data
      were retrieved from MEDLINE (via PubMed) using the keywords retraction of
      articles, retraction notice, and withdrawal of article in January 2014, and
      analysis of articles published in 2012 and 2013 was carried out. RESULTS: A total
      of 155 articles in 2012 and 182 in 2013 were retracted, and original articles
      followed by case reports constituted major part of it. The most cited reasons for
      retraction were mistakes, plagiarism, and duplicate submission, and the time
      interval between submission and retraction had reduced in 2013. CONCLUSION:
      Although retracted articles constitute the tip of an iceberg, they are still a
      matter of major concern in the scientific world. So, editors should follow the
      Committee on Publication Ethics (COPE) guidelines and make an effective strategy
      in order to reduce such misconduct, as it reflects very adversely not only in the
      scientific community but also in the general public.

PMID- 25767763
TI  - Gingival crevicular fluid: As a diagnostic marker in HIV positive patients.
AB  - OBJECTIVE: To determine the utility of gingival crevicular fluid (GCF) for the
      detection of anti-HIV antibodies in human immunodeficiency virus (HIV)-infected
      individuals using enzyme linked immunosorbent assay (ELISA) with respect to their
      CD4 counts. MATERIALS AND METHODS: The study was carried out between 37
      seropositive (37GCF, 10 saliva) and 37 seronegative (GCF) individuals for a
      period of 7-8 months in GDC Nagpur. Thirty-seven GCF and 10 whole saliva samples
      were collected from the same patient. GCF samples were collected from gingival
      crevice with the help of Kimble disposable microcapillary. Saliva was collected
      by asking the patient to bend forward. The drooling saliva was collected in a
      sterile bottle and stored at Minus 20 degrees C (-20 degrees C). After the
      clinical observations the data were collected and tabulated for statistical
      analysis. RESULTS: When compared with serum, the sensitivity, specificity, and
      positive and negative predictive values of GCF were 100% respectively.
      CONCLUSION: All the above findings are suggestive of GCF being a better
      diagnostic medium than saliva.

PMID- 25767764
TI  - Mutans streptococci estimation in saliva before and after consumption of
      probiotic curd among school children.
AB  - BACKGROUND: According to the World Health Organization, probiotics are live
      microorganisms which when administered in adequate amounts and confer a health
      benefit to the host. Use of probiotics in children to improve oral health may
      lead to non-pathogenic bacteria replacing cariogenic bacteria. Dairy foods like
      cheese, curd, and milk are considered useful vehicles for probiotic bacteria.
      AIM: To compare the levels of salivary mutans streptococci before and after
      consumption of probiotic curd. MATERIALS AND METHODS: Thirty school children of
      Mathura city who were caries free, in the age group of 12-14 years, were selected
      and divided equally into group I and II which were given 200 ml probiotic curd
      and normal curd for 7 days, respectively. Assessment of saliva samples was done
      at baseline, 1 h after consumption, and on the 7(th) day. Mitis Salivarius
      Bacitracin Agar was used for analysis. The number of colonies was counted and
      subjected to statistical analysis using unpaired Student's t-test. RESULTS: The
      study showed mark reduction in salivary mutans streptococci counts in saliva
      after 1 h and on the 7(th) day in the probiotic group. Results were found to be
      statistically significant (P <= 0.05) when the differences in the reduction of
      mutans streptococci counts with probiotic curd and normal curd at 1 h and on the
      7(th) day were compared. CONCLUSION: Pathogenic microorganisms could be displaced
      by probiotic bacteria. Thus, use of probiotic products could be exploited for the
      prevention of enamel demineralization.

PMID- 25767765
TI  - Oral health concerns with sweetened medicaments: Pediatricians' acuity.
AB  - BACKGROUND: Administration of sweetened medicaments poses many oral health
      related problems in children due to the lack of awareness among the pediatricians
      regarding their ill effects. PURPOSE: To assess pediatricians' awareness and
      attitudes toward the use of liquid pediatric medicines and their relationship
      with dental caries and erosion. MATERIALS AND METHODS: A cross-sectional
      descriptive study was conducted among the pediatricians residing in Nellore city.
      Data were obtained from 55 pediatricians using questionnaires. RESULTS: Among the
      respondents, 95.6% prescribed liquid medicaments, 51.1% expressed that they may
      be associated with dental effects, 60% were not aware regarding the sweetness of
      medicaments, whereas majority of them (77.8%) opined that children complained
      regarding the taste, 73.3% stated that sugar substitutes were used as sweetening
      agents, 70.9% believed that they were not acidic, 68.9% did not recommend
      brushing after intake of medicines, 90% failed to deliver oral health
      instructions, and 54.5% believed that lack of oral hygiene was a contributing
      factor for development of dental caries. CONCLUSION: Majority of the respondents
      prescribed liquid medicaments and were unaware regarding the sweetening agents
      and acidity, which cause ill effects on the dental hard tissues. Most of them
      neither recommended nor delivered oral hygiene instructions (OHI) after
      prescribing sweetened liquid medicaments. Hence, OHI should be delivered to
      enhance the oral health related quality of life in children.

PMID- 25767766
TI  - Career satisfaction among dental practitioners in Srikakulam, India.
AB  - BACKGROUND: This cross-sectional study was designed to measure the level and
      distribution of job satisfaction of registered dental practitioners and to
      explore the factors associated with it. MATERIALS AND METHODS: The study was
      conducted among 66 registered dentists in Srikakulam, India. Job satisfaction was
      measured by using a modified version of the Dentists Satisfaction Survey
      questionnaire. The statistical tests employed were "t" test and analysis of
      variance (ANOVA). Post hoc test (Scheffe test) was employed for multiple
      comparisons. RESULTS: The response rate was 82.5%. The mean score of overall job
      satisfaction among dentists was 3.08 out of 5. The most satisfying aspect was
      income (3.7) and the least satisfying aspect was staff (2.5). Overall
      satisfaction increased with age. Male practitioners showed less satisfaction with
      staff, income, and overall satisfaction and more satisfaction in professional
      relations and time, when compared to females. Job satisfaction was found to be
      more in practitioners with postgraduate qualification. CONCLUSION: This study
      suggests that patient relations, perception of income, personal time, and staff
      are the important factors for job satisfaction among dentists. The findings of
      this study will be helpful to policymakers to design plans in order to increase
      the level of job satisfaction.

PMID- 25767767
TI  - Evaluation of preparedness for medical emergencies at dental offices: A survey.
AB  - BACKGROUND: The best way to handle an emergency is to be prepared in advance. The
      purpose of this study was to assess the availability of medical emergency drugs
      at dental offices and to determine the level of knowledge and preparedness of
      dentists to manage medical emergencies at their dental offices. MATERIALS AND
      METHODS: A descriptive cross-sectional study was conducted from January to June
      2014 with 250 dental graduates to determine their knowledge and ability in the
      management of medical emergencies and assess availability of emergency drugs and
      equipments in dental offices in the Ahmedabad and Udaipur areas of India. The
      questionnaire consisted of mainly objective questions, requiring a simple yes or
      no reply. Mann-Whitney test was used for the analysis. A 95% confidence level was
      used and a P value of less than or equal to 0.05 was considered statistically
      significant. RESULTS: The results of our study showed that almost all the
      surveyed dentists (98%) enquired about medical history, but only 12% obtained
      filled health history proforma from patients regarding the above. Only 38.4%
      participants recorded the vital signs of patients before commencing any
      treatment. Also, 7.6% reported about having attended any workshops on emergency
      training or management programs. Emergency kits were available with only 24%
      participants and the available kits were assessed for the availability of
      emergency drugs. Also, 34% were confident about giving intramuscular injection
      and only 6.6% were sure about giving intravenous injections. The P value was
      found to be highly statistically significant. CONCLUSION: The results of our
      study reflect an alarming situation about the capability of dentists to deal with
      such conditions.

PMID- 25767768
TI  - Caries experience and its association with weight status among 8-year-old
      children in Qingdao, China.
AB  - OBJECTIVES: Childhood obesity/underweight status and caries are both important
      public health problems. This study aims to investigate the caries status and its
      association with body weight in 8-year-old children in Qingdao, China. MATERIALS
      AND METHODS: We initiated a cross-sectional investigation on 744 children aged 8
      years during the Oral Health Survey in 2012. Dental caries assessments were
      carried out and weight status was recorded accordingly. The resulting caries
      status including caries prevalence, dmft (deciduous dentition), and (dmft + DMFT)
      (mixed dentition), as well as BMI indices were analyzed for comparison and
      correlation. RESULTS: The prevalence of dental caries among the 744 children aged
      8 years participating in this survey was 86.3%. The caries status represented by
      dmft (deciduous dentition) and (dmft + DMFT) (mixed dentition) values was 4.31
      and 4.85, respectively, and the restoration rate was extremely low, which was no
      more than 3.0%. Significant difference was found in dmft/(dmft + DMFT) values
      between different BMI groups, and underweight individuals were found to have the
      highest dmft/(dmft + DMFT) value. An inverse relationship between body BMI and
      dmft/(dmft + DMFT) index was identified based on Pearson's correlation.
      CONCLUSIONS: A severe state of caries disease was revealed in 8-year-old children
      in the Chinese city of Qingdao, for whom urgent dental intervention and treatment
      were needed. Furthermore, underweight individuals were found with the most severe
      caries experience, indicating caries may affect the development and growth of the
      afflicted children. Thus, more emphasis should be placed on improving their
      dental health, with caries prevention being given the priority.

PMID- 25767769
TI  - Prevalence of dental caries and oral hygiene status of a screened population in
      Port Harcourt, Rivers State, Nigeria.
AB  - OBJECTIVES: The study was designed to determine the prevalence of dental caries
      and partial edentulism, in addition to assessing the oral hygiene status and
      restorative care among adults in a community-based outreach program in Port
      Harcourt. MATERIALS AND METHODS: A cross-sectional study was conducted among
      adults who participated in oral health screening program, which took place in
      Alakahia and Obigbo rural communities in Port Harcourt, Rivers State, Nigeria.
      After a brief oral health education, clinical examination was conducted and the
      diagnosis of caries was made based on the guidelines laid down by World Health
      Organization. Prevalence of caries was measured using decayed missing and filled
      teeth (DMFT) index, and oral hygiene status was assessed using the OHI-S. The
      restorative index [(F/F + D) *100] was also calculated and the sociodemographic
      factors of the subjects were noted. Chi-square test, independent t-test and
      descriptive statistic were employed for analysis. RESULTS: One fifty-five females
      (53.8%) and 133 males (46.2%) attended the events and their mean age was 29.3 +/-
      10.5 years. About one-third of the participants (35.1%) presented with dental
      caries. The mean DMFT for the whole group was 0.67 +/- 2.0. The restorative index
      for the subjects was 26.8%. The oral hygiene status of most of the participants
      was fair. This was significantly better in females than in males (P = 0.002).
      CONCLUSION: Although about one-third of the participants had dental caries, only
      a quarter of them had received restorative care. Most of the respondents had fair
      and poor oral hygiene, this suggests the need to educate and motivate the
      community toward adopting and maintaining positive oral health attitudes and
      practices.

PMID- 25767770
TI  - Premolar extraction in orthodontics: Does it have any effect on patient's facial
      height?
AB  - OBJECTIVES: Facial esthetics is an important part of the orthodontic treatment.
      Many cases frequently require premolar extraction, either for relief of crowding
      or for profile change. Supposedly, extraction provides some vertical reduction.
      This investigation challenges the clinical effects of such treatment protocols.
      PATIENTS AND METHODS: This was a retrospective and quasi-experimental study.
      Records of 60 patients in their post-pubertal age were randomly selected for this
      study. The criteria for case selection were: Class II Division I malocclusion
      with either two upper or four upper and lower first premolars extraction.
      Patients were not vertical-sensitive type of face. Pre- and post-treatment X-rays
      were scanned and digitized with Dolphin V 10.0 software. The X-rays of both
      groups were compared based upon the following cephalometric measurements: Lower
      anterior facial height (LAFH), Me-PP, Pal-MeGe, LAFH/total anterior facial height
      (TAFH) * 100, upper anterior facial height (UAFH)/TAFH * 100, U6 to PP, L6 to MP,
      and U6D-PTV. RESULTS: In the four bicuspid group, a statistically significant
      increase was observed in all measurements: 2.53 mm increase in LAFH (P <= 0.04),
      2.92 mm increase in Me-PP (P <= 0.01), 0.65 degrees  increase in Pal-MeGe (P <=
      0.02), 0.66 degrees  increase in LAFH/TAFH * 100 (P <= 0.01), 1.26 mm increase in
      U6 to PP (P <= 0.02), 1.96 mm increase in L6 to MP (P <= 0.002), and 3.06 mm
      increase in U6D-PTV (P <= 0.0001). But a decrease of 0.66 degrees  in UAFH/TAFH *
      100 (P <= 0.01) was observed. In the two bicuspid group, a significant increase
      was generally recorded: 2.06 mm increase in LAFH (P <= 0.05), 1.19 degrees 
      increase in Pal-MeGe (P <= 0.02), 1.39 mm increase in L6 to MP (P <= 0.002), and
      2.37 mm increase in U6D-PTV (P <= 0.004). CONCLUSIONS: The results of this study
      are indicative of no change in patient's facial height with bicuspid extraction.
      In fact, extrusive effect of all types of tooth movement mostly overcomes the
      benefits of "wedging effect concept."

PMID- 25767771
TI  - Comparative evaluation of four transport media for maintaining cell viability in
      transportation of an avulsed tooth - An in vitro study.
AB  - OBJECTIVES: The study was performed to compare and evaluate the efficacy of four
      experimental storage media (Hank's balanced salt solution, Ringer's lactate
      solution, tender coconut water, and green tea extract) for maintaining cell
      viability of human periodontal cells at different time intervals of 15 min 30
      min, 60 min, and 90 min. MATERIALS AND METHODS: Human periodontal cells were
      cultured and stored in the four media. After 15 min 30 min, 60 min, and 90 min,
      the different media were examined under optical microscope and viabilities
      analyzed using an optical calorimeter. Mean and standard deviation were estimated
      from the results that were statistically analyzed using one-way analysis of
      variance (ANOVA) to identify the significant groups. RESULTS: The results
      indicated that there was no difference in cell viability between the four media
      up to a period of 60 min, whereas green tea extract showed a lower cell viability
      after 90 min. CONCLUSION: Within the limitations of the present study, it appears
      that due to superior osmolality, cost effectiveness, and easier availability,
      Ringer's lactate, tender coconut water, and green tea extract can be used as
      alternate storage media for avulsed tooth.

PMID- 25767772
TI  - Clinical implications of circulating tumor cells of breast cancer patients: role
      of epithelial-mesenchymal plasticity.
AB  - There is increasing interest in circulating tumor cells (CTCs) due to their
      purported role in breast cancer metastasis, and their potential as a "liquid
      biopsy" tool in breast cancer diagnosis and management. There are, however,
      questions with regards to the reliability and consistency of CTC detection and to
      the relationship between CTCs and prognosis, which is limiting their clinical
      utility. There is increasing acceptance that the ability of CTCs to alter from an
      epithelial to mesenchymal phenotype plays an important role in determining the
      metastatic potential of these cells. This review examines the phenotypic and
      genetic variation, which has been reported within CTC populations. Importantly,
      we discuss how the detection and characterization of CTCs provides additional and
      often differing information from that obtained from the primary tumor, and how
      this may be utilized in determining prognosis and treatment options. It has been
      shown for example that hormone receptor status often differs between the primary
      tumor and CTCs, which may help to explain failure of endocrine treatment. We
      examine how CTC status may introduce alternative treatment options and also how
      they may be used to monitor treatment. Finally, we discuss the most interesting
      current clinical trials involving CTC analysis and note further research that is
      required before the breast cancer "liquid biopsy" can be realized. 

PMID- 25767774
TI  - All arthroscopic stabilization of acute acromioclavicular joint dislocation with
      fiberwire and endobutton system.
AB  - INTRODUCTION: acromioclavicular (AC) joint dislocation is common in athletes and
      in contact sports and about 9% of shoulder injuries involves this joint. The
      majority of these AC lesions can be successfully treated conservatively but high
      grade dislocation and some cases of type III dislocation need a surgical
      treatment. Many different operative techniques have been described over the
      years. The purpose of this study is to evaluate the results of arthroscopic
      stabilization of AC joint dislocation with TightRope(r) system. MATERIALS AND
      METHODS: nineteen patients with acute AC dislocation were treated by arthroscopic
      fixation with TightRope(r) system. Any associated lesions were repaired. All
      patients were assessed before surgery (T0), at 3 months (T1), at 6 months (T2)
      and at 1 year after the surgery (T3) using a visual analogic scale (VAS) and
      Constant-Murley Score (CMS). All patients were evaluated with X-ray. RESULTS: six
      AC-joint dislocations involved the right shoulder and thirteen the left shoulder.
      Ten were type III dislocation, three were type IV and six were type V
      dislocation. We found a statistically significant reduction of pain (p< 0.01) at
      T1 compared to the pretreatment scores. The CMS measures showed an improvement
      between T1, T2 and T3, but the difference was statistically significant only
      between T1 and T3 (p= 0.017). The postoperative X-Ray of the shoulder showed a
      good reduction of the AC joint dislocation. We had 1 case of recurrence and 2
      cases of loss of intraoperative reduction. CONCLUSION: arthroscopic technique for
      acute AC joint dislocations with the use of the TightRope(r) device is minimally
      invasive and it allows an anatomic restoration of the joint. It is a safe and
      effective procedure ensuring stable AC joint reconstruction and good cosmetic
      results.

PMID- 25767775
TI  - Skin closure after arthroscopy utilizing a pull-out bow-tie subcuticular suture.
AB  - BACKGROUND: suturing techniques employed to close subcuticular surgical incisions
      are varied. PURPOSE: we present the "bow-tie" stitch, which is removed by pulling
      one side of the stitch with no need for sharp object stitch cutting. The stitch
      results in good approximation and scarring while enabling proper oozing. METHODS:
      we have used this suture repeatedly for wound closure after hip and knee
      arthroscopy; its application to other superficial skin closures is easily
      appreciated. RESULTS: this method of skin closure allows for ease of tying for
      the surgeon, aesthetically pleasing results for the patient, pain-free suture
      removal, no risk of suture knots becoming embedded in healing tissue, and
      decreased risk of infection and damage to skin, as instruments are not required
      for suture removal.

PMID- 25767773
TI  - Epithelial-to-Mesenchymal Plasticity Harnesses Endocytic Circuitries.
AB  - The ability of cells to alter their phenotypic and morphological characteristics,
      known as cellular plasticity, is critical in normal embryonic development and
      adult tissue repair and contributes to the pathogenesis of diseases, such as
      organ fibrosis and cancer. The epithelial-to-mesenchymal transition (EMT) is a
      type of cellular plasticity. This transition involves genetic and epigenetic
      changes as well as alterations in protein expression and post-translational
      modifications. These changes result in reduced cell-cell adhesion, enhanced cell
      adhesion to the extracellular matrix, and altered organization of the
      cytoskeleton and of cell polarity. Among these modifications, loss of cell
      polarity represents the nearly invariable, distinguishing feature of EMT that
      frequently precedes the other traits or might even occur in their absence. EMT
      transforms cell morphology and physiology, and hence cell identity, from one
      typical of cells that form a tight barrier, like epithelial and endothelial
      cells, to one characterized by a highly motile mesenchymal phenotype. Time
      resolved proteomic and phosphoproteomic analyses of cells undergoing EMT recently
      identified thousands of changes in proteins involved in many cellular processes,
      including cell proliferation and motility, DNA repair, and - unexpectedly -
      membrane trafficking (1). These results have highlighted a picture of great
      complexity. First, the EMT transition is not an all-or-none response but rather a
      gradual process that develops over time. Second, EMT events are highly dynamic
      and frequently reversible, involving both cell-autonomous and non-autonomous
      mechanisms. The net results is that EMT generates populations of mixed cells,
      with partial or full phenotypes, possibly accounting (at least in part) for the
      physiological as well as pathological cellular heterogeneity of some tissues.
      Endocytic circuitries have emerged as complex connectivity infrastructures for
      numerous cellular networks required for the execution of different biological
      processes, with a primary role in the control of polarized functions. Thus, they
      may be relevant for controlling EMT or certain aspects of it. Here, by discussing
      a few paradigmatic cases, we will outline how endocytosis may be harnessed by the
      EMT process to promote dynamic changes in cellular identity, and to increase
      cellular flexibility and adaptation to micro-environmental cues, ultimately
      impacting on physiological and pathological processes, first and foremost cancer
      progression. 

PMID- 25767776
TI  - Treatment of the calcific tendinopathy of the rotator cuff by ultrasound-guided
      percutaneous needle lavage. Two years prospective study.
AB  - PURPOSE: to evaluate the short and long term effectiveness of ultrasonography
      (US)-guided percutaneous needle lavage in calcific tendinopathy of the rotator
      cuff. To study the evolution of the size of calcifications and pain in the two
      years after treatment. METHODS: a 2 year longitudinal prospective study is
      carried out after applying the UGPL technique on a number of patients diagnosed
      with calcific tendinitis of the rotator cuff. Clinical, ultrasound and radiology
      follow-up controls were performed, 3 months, 6 months, one year and two years
      after the treatment. The Visual Analog Scale (VAS) was used to assess the pain.
      The degree and point of pain is selected on a 10cm line, arranged horizontally or
      vertically. The "0" represents no pain and "10" represents worst pain. The
      population studied was made up of 121 patients that required our service as a
      result of suffering from a painful shoulder. RESULTS: the pain (VAS) and the size
      of the calcification significantly decreased with the application of the
      technique (p< 0,001 in both cases) and regardless of the sex (p: 0.384 for pain
      and p: 0.578 for the size of the calcification). This occurred from the first
      check-up (3 months) and was maintained for two year. CONCLUSION: we consider this
      technique to be a valid alternative as a first-choice treatment of calcific
      tendinitis of the shoulder. The intervention is simple, cost-effective, does not
      require hospitalization, involves no complications, rehabilitation treatment is
      not required and it shows very few side effects without sequelae, significantly
      reducing the size of the calcification and pain in the majority of patients.

PMID- 25767777
TI  - Exercise protocol induces muscle, tendon, and bone adaptations in the rat
      shoulder.
AB  - BACKGROUND: a rat model of supraspinatus overuse has suggested mechanisms
      governing tendon degeneration; however, delineating which changes are pathologic
      or simply physiologic adaptations to increased loading remains a question. The
      objective of this study was to develop and characterize a rat exercise model that
      induces systemic and local shoulder adaptations without mechanical injury to the
      supraspinatus tendon. METHODS: exercise rats completed a treadmill training
      protocol for 12 weeks. Body, fat pad, and heart weights were determined.
      Supraspinatus tendon collagen content, cross-sectional area, and mechanical
      properties were measured. Supraspinatus muscle cross-sectional area, weight, and
      the expression of mitochondrial oxidative phosphorylation (OXPHOS) proteins were
      measured. Humeri were analyzed with MUCT and mechanically tested. RESULTS:
      exercise decreased fat pad mass. Supraspinatus muscle hypertrophied and had
      increased OXPHOS proteins. Humerus trabecular bone had increased anisotropic
      orientation, and cortical bone showed increased bone and tissue mineral density.
      Importantly, the supraspinatus tendon did not have diminished mechanical
      properties, indicating that this protocol was not injurious to the tendon.
      CONCLUSION: this study establishes the first rat exercise protocol that induces
      adaptations in the shoulder. Future research can use this as a comparison model
      to study how the supraspinatus tendon adapts to loading and undergoes
      degeneration with overuse.

PMID- 25767778
TI  - Surgical and non-surgical treatment of frozen shoulder. Survey on surgeons
      treatment preferences.
AB  - BACKGROUND: frozen shoulder is a common condition and its management can be
      surgical or non-surgical. The aim was to determine current trends in the
      management of frozen shoulder amongst surgical members of the British Elbow and
      Shoulder Society (BESS). METHODS: a single electronic questionnaire was emailed
      to surgical members of the BESS. Participants were asked about their surgical and
      non-surgical treatments of choice and the reasoning behind that, as well as which
      components of arthroscopic arthrolysis they favoured. RESULTS: 87 BESS members
      completed the questioner. The majority of respondents used physiotherapy as their
      preferred means of non-surgical management while arthroscopic arthrolysis was the
      most frequently used surgical intervention. A substantial proportion of surgeons
      based their choice on personal experience and training rather than published
      evidence. CONCLUSIONS: management of frozen shoulder amongst surgeons varies
      substantially and is highly based on personal experience and training rather than
      strong evidence. Arthroscopic arthrolysis is a heterogeneous procedure with a
      wide variation in the use of its various components. Our results highlight the
      need for high quality clinical trials to compare the management options
      available.

PMID- 25767779
TI  - Tendon transfer for irreparable rotator cuff tears: indications and surgical
      rationale.
AB  - BACKGROUND: treatment of symptomatic irreparable rotator cuff tears is extremely
      challenging because, at present, there are no ideal solutions to this problem.
      Many patients respond favorably to nonsurgical treatment. However, when
      conservative measures fail to improve the patient's pain and disability, surgery
      should be considered. METHODS: different surgical techniques are available and
      the choice of the most appropriate procedure depends on the presenting symptoms,
      age of the patient, functional demand, medical comorbidities, joint stability and
      presence of arthritic changes. The transposition of the surrounding muscles to
      replace the rotator cuff function represents a viable option in the treatment of
      younger patients without glenohumeral osteoarthritis and with severe functional
      limitation. PURPOSE: aim of this study is to give an overview of the currently
      available evidence regarding tendon transfer procedures for irreparable rotator
      cuff tears.

PMID- 25767780
TI  - Diverse muscle architecture adaptations in a rabbit tibial lengthening model.
AB  - BACKGROUND: during limb lengthening, muscles are thought to increase the number
      of sarcomeres. However, this adaptation may differ among muscles with diverse
      architecture. PURPOSE: this study wish to clarify the differences in muscle
      adaptation in a rabbit model of tibial lengthening. METHODS: twelve rabbits
      underwent tibial lengthening (0.7 mm/day for 4 weeks), with the contralateral
      limb serving as a control, and were euthanized after either the lengthening or
      the consolidation period. Six muscles around the tibia were investigated in terms
      of muscle belly length, muscle weight, sarcomere length and serial sarcomere
      number. RESULTS: muscle belly length increased in all the lengthened muscles. No
      increases in muscle mass were noted. Sarcomere length increased in the ankle
      plantar-flexors and was kept longer than the optimal sarcomere length after the
      consolidation period. Nevertheless, significant increases in sarcomere number
      were observed in two ankle plantar-flexors. CONCLUSION: this study demonstrated
      that muscle belly length largely adapted to the lengthening. The increase in
      sarcomere number did not match the increase in muscle belly length. We estimated
      that elongation of the intramuscular aponeuroses is another mechanism of the
      adaptation in addition to the increase in sarcomere number.

PMID- 25767781
TI  - The development of swimming power.
AB  - PURPOSE: the aim of this study was to investigate the effects of the transfer
      strength training method on swimming power. METHODS: twenty male swimmers
      "master" were randomly allocated to strength (n= 10, ST) and swimming training
      (n=10, SW) groups. Both groups performed six-weeks training based on swimming
      training for SW and strength training which consisted in a weight training
      session immediately followed by the maximum swimming velocity. The performance in
      both groups was assessed by Maximal-Mechanical-External-Power (MMEP) before and
      after the six-weeks period, using a custom ergometer that provided force,
      velocity, and power measurement in water. RESULTS: a significant increased MMEP
      in ST group (5.73% with p< 0.05) was obtained by an increased strength (11.70%
      with p< 0.05) and a decreased velocity (4.99% with p> 0.05). Conversely, in the
      SW group there was a decreased in MMEP (7.31%; p< 0.05), force and velocity
      (4.16%, and 3.45; respectively p> 0.05). CONCLUSION: this study showed that the
      transfer training method, based on combination of weight training (in dry
      condition) immediately followed by fast swim (in water) significantly improves
      swimming-power in master.

PMID- 25767782
TI  - Matrix metalloproteinase-2 plays a critical role in overload induced skeletal
      muscle hypertrophy.
AB  - BACKGROUND: extracellular matrix (ECM) components are instrumental in maintaining
      homeostasis and muscle fiber functional integrity. Skeletal muscle hypertrophy is
      associated with ECM remodeling. Specifically, recent studies have reported the
      involvement of matrix metalloproteinases (MMPs) in muscle ECM remodeling.
      However, the functional role of MMPs in muscle hypertrophy remains largely
      unknown. METHODS: in this study, we examined the role of MMP-2 in skeletal muscle
      hypertrophy using a previously validated method where the plantaris muscle of
      mice were subjected to mechanical overload due to the surgical removal of
      synergist muscles (gastrocnemius and soleus). RESULTS: following two weeks of
      overload, we observed a significant increase in MMP-2 activity and up-regulation
      of ECM components and remodeling enzymes in the plantaris muscles of wild-type
      mice. However, MMP-2 knockout mice developed significantly less hypertrophy and
      ECM remodeling in response to overload compared to their wild-type littermates.
      Investigation of protein synthesis rate and Akt/mTOR signaling revealed no
      difference between wild-type and MMP-2 knockout mice, suggesting that a
      difference in hypertrophy was independent of protein synthesis. CONCLUSION: taken
      together, our results suggest that MMP-2 is a key mediator of ECM remodeling in
      the setting of skeletal muscle hypertrophy.

PMID- 25767783
TI  - Treatment algorithm for chronic lateral ankle instability.
AB  - INTRODUCTION: ankle sprains are a common sports-related injury. A 20% of acute
      ankle sprains results in chronic ankle instability, requiring surgery. Aim of
      this paper is to report the results of a series of 38 patients treated for
      chronic lateral ankle instability with anatomic reconstruction. MATERIALS AND
      METHODS: thirty-eight patients were enrolled in the study. Seventeen patients
      underwent a surgical repair using the Brostrom-modified technique, while the
      remaining underwent anatomic reconstruction with autologous or allogenic graft.
      RESULTS: at a mean follow-up of 5 years the AOFAS score improved from 66.1 +/-
      5.3 to 92.2 +/- 5.6. DISCUSSION: the findings of this study confirm that anatomic
      reconstruction is an effective procedure with satisfactory subjective and
      objective results which persist at long-term follow-up along with a low
      complication rate. No differences, in term of clinical and functional outcomes,
      were observed between the Brostrom-modified repair and the anatomic
      reconstruction technique. LEVEL OF EVIDENCE: level IV.

PMID- 25767784
TI  - Platelet-rich plasma treatment improves outcomes for chronic proximal hamstring
      injuries in an athletic population.
AB  - BACKGROUND: chronic proximal hamstring tendinopathies is a disabling activity
      related condition. Currently, there is no well-accepted or extensively documented
      non-operative treatment option that provides consistently successful results.
      PURPOSE: to evaluate the efficacy of ultrasound guided platelet-rich plasma
      injections in treating chronic proximal hamstring tendinopathies. METHODS: a
      total of 18 consecutive patients were retrospectively analyzed. All patients
      received a single injection of platelet rich plasma via ultra-sound guidance by a
      single radiologist. Outcome measures included a questionnaire evaluating previous
      treatments, visual analog scale (VAS) for pain, subjective improvement, history
      of injury, and return to activity. RESULTS: the patient population included 12
      females and 6 males. The average age at the time of the injection was 42.6 years
      (19-60). Provocative activities included running, biking, swimming. The average
      body mass index of patients was 22.9 (17.2-30.2). The average time of chronic
      pain prior to receiving the first injection was 32.6 months (6-120). All patients
      had attempted other forms of non-surgical treatment prior to entering the study.
      The average VAS pre-injection was 4.6 (0-8). Six months after the injection,
      10/18 patients had 80% or greater improvement in their VAS. Overall, the average
      improvement was 63% (5-100). The only documented side effect was post-injection
      discomfort that resolved within seventy-two hours. CONCLUSION: chronic hamstring
      tendinopathy is a debilitating condition secondary to the pain, which limits an
      athlete's ability to perform. For refractory cases of chronic insertional
      proximal hamstring injuries, platelet-rich plasma injections are safe and show
      benefit in the majority of patients in our study, allowing return to pre-injury
      activities. STUDY DESIGN: Case series; Level of evidence, 4.

PMID- 25767785
TI  - Posterior cruciate ligament reconstruction with "all-inside" technique: a
      technical note.
AB  - INTRODUCTION: posterior cruciate ligament (PCL) injuries are an increasingly
      recognized cause of knee instability in the practice of orthopaedic surgery and
      sports medicine. Clinical interest in these injuries has been increasing over the
      last several decades as knowledge and understanding of the biomechanical
      consequences and surgical reconstruction options have progressed. These injuries
      can be extremely challenging for the treating physician as substantial
      controversy exists regarding the optimal management of this problem. There has
      also been increasing interest and recognition of the importance of secondary
      stabilizing structures, including the posterolateral and posteromedial corner
      injuries as well as the issues with malalignment that must also be addressed at
      the time of PCL surgery to optimize results. Thanks to the continuous research
      for a correct anatomical placement and new systems of fixation, we can now
      perform the tibial and femoral bone tunnel more easily and safely by retrograde
      out-in approach with a special "drill-pin". CONCLUSION: this technique provides a
      graduated precise execution of the tunnels. New methods were also developed to
      determine the so-called "second-generation cortical suspensory fixations" that
      have the feature of being "Adjustable": shortens implant by pulling on strands to
      allow cinching graft passing and tensioning button to regulate their length after
      fixation and then to create tension in the new graft, once introduced into the
      joint.

PMID- 25767786
TI  - You are not walking alone in the PRP consensus road.

PMID- 25767787
TI  - Merchants shall be expelled from the Temple: the PRGF((r)) (Plasma-Preparation
      Rich in Growth Factors)-Endoret((r)) case.

PMID- 25767788
TI  - The effect of Norouz holiday on anthropometric measures and body composition.
AB  - BACKGROUND: This study examined the effect of holiday season on the
      anthropometric measures in Shariati hospital staff. METHODS: This study was
      conducted in 2014 on 66 subjects, aged 21-68 years. Weight, height, waist
      circumference (WC), hip circumference (HC), waist -to-hip ratio (WHR), waist-to-
      height ratio (WHtR) and physical activity were measured. Bioelectrical impedance
      analysis (BIA) method and the Tanita body composition analyzer were used to
      analyze body composition. RESULTS: In this study, 80.3% of subjects were female
      and 19.7% were male. The mean age of subjects was 39.5 (SD: 9.7) years (range: 21
      68). The percentage of overweight and obesity in the study population were 40.9%
      and 12.1%, respectively. After the holiday, participants gained 0.58 kg of weight
      and 0.19 units of BMI) P < 0.001). The average of WC, WHR and WHtR also increased
      after the holiday; however they were not statistically significant. Basal
      metabolic rate and fat free mass raised significantly, but the amount of fat mass
      decreased after the holiday. CONCLUSION: The holiday season is a critical period
      for weight gain and body fat. It's highly recommended to weight daily during the
      holiday season and to increase their physical activity while limiting high
      calorie foods.

PMID- 25767789
TI  - Immune cells: more than simple carriers for systemic delivery of oncolytic
      viruses.
AB  - Oncolytic virotherapy on its own has numerous drawbacks, including an inability
      of the virus to actively target tumor cells and systemic toxicities at the high
      doses necessary to effectively treat tumors. Addition of immune cell-based
      carriers of oncolytic viruses holds promise as a technique in which oncolytic
      virus can be delivered directly to tumors in smaller and less toxic doses.
      Interestingly, the cell carriers themselves have also demonstrated antitumor
      effects, which can be augmented further by tailoring the appropriate oncolytic
      virus to the appropriate cell type. This review discusses the multiple factors
      that go into devising an effective, cell-based delivery system for oncolytic
      viruses.

PMID- 25767791
TI  - Feeding modalities and the onset of the neonatal abstinence syndrome.
AB  - Breast milk has been reported to ameliorate the severity and outcome of neonatal
      abstinence syndrome (NAS). The mechanism of this beneficial effect of breast milk
      on NAS remains unclear, as the negligible amount of methadone transmitted via
      breast milk is unlikely to have an impact on NAS. The aim of this study was to
      compare the impact of different feeding modalities on the onset of NAS. A
      retrospective medical record review was conducted on 194 methadone-maintained
      mother/infant dyads. Infants were categorized on the first 2 days of life as
      predominantly breastfed, fed expressed human breast milk (EBM), or formula fed.
      The feeding categories were then analyzed using the onset of NAS as the outcome
      measure. After adjusting for confounders, there was no significant effect of the
      modality of feeding on the rates of NAS requiring treatment (p = 0.11).
      Breastfeeding significantly delayed the onset of NAS (p = 0.04). The act of
      breastfeeding in the first 2 days of life had no effect on whether an infant
      required treatment for NAS when compared to those fed EBM or formula. This only
      suggests that the advantages of breastfeeding on NAS cannot be substantiated in a
      small cohort and should not discourage breastfeeding. 

PMID- 25767790
TI  - Testosterone replacement alters the cell size in visceral fat but not in
      subcutaneous fat in hypogonadal aged male rats as a late-onset hypogonadism
      animal model.
AB  - BACKGROUND: Patients with late-onset hypogonadism (LOH) benefit from testosterone
      replacement by improvement in the parameters of the metabolic syndrome, but fat
      cell morphology in these patients is still unclear. This study aims to determine
      the effect of testosterone replacement on the morphology of fat cells in
      subcutaneous and visceral adipose tissue and on erectile function in hypogonadal
      aged male rats as a model of LOH. METHODS: Ten male Sprague-Dawley rats aged 20
      22 months were randomly allocated to two groups, ie, aged male controls (control
      group, n=5) and aged males treated with testosterone replacement therapy (TRT
      group, n=5). Testosterone enanthate 25 mg was injected subcutaneously every 2
      weeks for 6 weeks. At 6 weeks, the intracavernous pressure (ICP) and mean
      arterial blood pressure (MAP) ratio was assessed. Visceral and subcutaneous
      adipose tissue specimens were collected and analyzed using Image-J software.
      RESULTS: Body weight at 2, 4, and 6 weeks after TRT was 800.0+/-35.4 g, 767.5+/
      46.3 g, and 780+/-40.4 g, respectively (not statistically significant). The
      ICP/MAP ratio was 0.341+/-0.015 in the TRT group and 0.274+/-0.049 in the control
      group (not statistically significant). The median subcutaneous fat cell size was
      4.85*10(3) (range 0.85-12.53*10(3)) MUm(2) in the control group and 4.93*10(3)
      (range 6.42-19.7*10(3)) MUm(2) in the TRT group (not statistically significant).
      In contrast, median visceral fat cell size was significantly smaller in the TRT
      group (4.93*10(3) MUm(2) [range 0.51-14.88*10(3)]) than in the control group
      (6.08*10(3) MUm(2) [0.77-19.97*10(3)]; P<0.001, Mann-Whitney U test). CONCLUSION:
      This is the first study clearly indicating that TRT can decrease visceral fat
      cell size, which is a key modulator in the metabolic syndrome. However, a short
      course of TRT could not improve the ICP response in hypogonadal aged male rats.
      Further investigation is necessary to clarify the exact rationale of TRT on the
      visceral fat cell.

PMID- 25767792
TI  - Leadership in public health: new competencies for the future.

PMID- 25767793
TI  - Undergraduate public health, lessons learned from undergraduate health
      administration education.

PMID- 25767794
TI  - On the Slow Diffusion of Point-of-Care Systems in Therapeutic Drug Monitoring.
AB  - Recent advancements in point-of-care (PoC) technologies show great transformative
      promises for personalized preventative and predictive medicine. However, fields
      like therapeutic drug monitoring (TDM), that first allowed for personalized
      treatment of patients' disease, still lag behind in the widespread application of
      PoC devices for monitoring of patients. Surprisingly, very few applications in
      commonly monitored drugs, such as anti-epileptics, are paving the way for a PoC
      approach to patient therapy monitoring compared to other fields like intensive
      care cardiac markers monitoring, glycemic controls in diabetes, or bench-top
      hematological parameters analysis at the local drug store. Such delay in the
      development of portable fast clinically effective drug monitoring devices is in
      our opinion due more to an inertial drag on the pervasiveness of these new
      devices into the clinical field than a lack of technical capability. At the same
      time, some very promising technologies failed in the clinical practice for
      inadequate understanding of the outcome parameters necessary for a relevant
      technological breakthrough that has superior clinical performance. We hope, by
      over-viewing both TDM practice and its yet unmet needs and latest advancement in
      micro- and nanotechnology applications to PoC clinical devices, to help bridging
      the two communities, the one exploiting analytical technologies and the one
      mastering the most advanced techniques, into translating existing and forthcoming
      technologies in effective devices. 

PMID- 25767795
TI  - Transcription interference and ORF nature strongly affect promoter strength in a
      reconstituted metabolic pathway.
AB  - Fine tuning of individual enzyme expression level is necessary to alleviate
      metabolic imbalances in synthetic heterologous pathways. A known approach
      consists of choosing a suitable combination of promoters, based on their
      characterized strengths in model conditions. We questioned whether each step of a
      multiple-gene synthetic pathway could be independently tunable at the
      transcription level. Three open reading frames, coding for enzymes involved in a
      synthetic pathway, were combinatorially associated to different promoters on an
      episomal plasmid in Saccharomyces cerevisiae. We quantified the mRNA levels of
      the three genes in each strain of our generated combinatorial metabolic library.
      Our results evidenced that the ORF nature, position, and orientation induce
      strong discrepancies between the previously reported promoters' strengths and the
      observed ones. We conclude that, in the context of metabolic reconstruction, the
      strength of usual promoters can be dramatically affected by many factors. Among
      them, transcriptional interference and ORF nature seem to be predominant. 

PMID- 25767797
TI  - A novel function of RIP1 in postnatal development and immune homeostasis by
      protecting against RIP3-dependent necroptosis and FADD-mediated apoptosis.
AB  - RIP1 is an adaptor kinase originally identified as being able to associate with
      TNFR1 and Fas, and is later shown to be involved in signaling induced by TLRs.
      Major signaling pathways regulated by RIP1 include necroptosis, apoptosis, and
      pro-survival/inflammation NF-kappaB activation. Previous studies show that RIP1
      deficiency has no effect on mouse embryogenesis, but blocks postnatal
      development. This phenotype could not readily be explained, since mice lacking
      TNFR1, Fas, or TLRs show no apparent developmental defect. Certain types of RIP1
      deficient cells are hypersensitive to TNF-induced apoptosis. However, in our
      previous study, deletion of the apoptotic adaptor protein, FADD, provides
      marginal improvement of postnatal development of rip1 (-/-) mice. Remarkably, the
      current data shows that haploid insufficiency of RIP3, a known mediator of
      necroptosis, allowed survival of rip1 (-/-) fadd (-/-) mice beyond weaning age,
      although the resulting rip1(-/-)fadd(-/-) rip3(+/-) mice were significant smaller
      in size and weight. Moreover, complete absence of RIP3 further improved postnatal
      development of the resulting rip1 (-/-) fadd (-/-) rip3 (-/-) mice, which display
      normal size and weight. In such triple knockout (TKO) mice, lymphocytes underwent
      normal development, but progressively accumulated as mice age. This
      lymphoproliferative (lpr) disease in TKO mice is, however, less severe than that
      of fadd(-/-)rip3 (-/-) double knockout mice. In total, the data show that the
      postnatal developmental defect in rip1 (-/-) mice is due in part to FADD-mediated
      apoptosis as well as RIP3-dependent necroptosis. Moreover, the function of RIP1
      contributes to development of lpr diseases. 

PMID- 25767796
TI  - Rethinking gene regulatory networks in light of alternative splicing,
      intrinsically disordered protein domains, and post-translational modifications.
AB  - Models for genetic regulation and cell fate specification characteristically
      assume that gene regulatory networks (GRNs) are essentially deterministic and
      exhibit multiple stable states specifying alternative, but pre-figured cell
      fates. Mounting evidence shows, however, that most eukaryotic precursor RNAs
      undergo alternative splicing (AS) and that the majority of transcription factors
      contain intrinsically disordered protein (IDP) domains whose functionalities are
      context dependent as well as subject to post-translational modification (PTM).
      Consequently, many transcription factors do not have fixed cis-acting regulatory
      targets, and developmental determination by GRNs alone is untenable. Modeling
      these phenomena requires a multi-scale approach to explain how GRNs operationally
      interact with the intra- and intercellular environments. Evidence shows that AS,
      IDP, and PTM complicate gene expression and act synergistically to facilitate and
      promote time- and cell-specific protein modifications involved in cell signaling
      and cell fate specification and thereby disrupt a strict deterministic GRN
      phenotype mapping. The combined effects of AS, IDP, and PTM give proteomes
      physiological plasticity, adaptive responsiveness, and developmental versatility
      without inefficiently expanding genome size. They also help us understand how
      protein functionalities can undergo major evolutionary changes by buffering
      mutational consequences. 

PMID- 25767798
TI  - The Helicobacter pylori dupA: A Novel Biomarker for Digestive Diseases.

PMID- 25767799
TI  - Gut microbiota: the next-gen frontier in preventive and therapeutic medicine?
AB  - Our gut harbors an extremely diverse collection of trillions of microbes that,
      besides degrading the complex dietary constituents, execute numerous activities
      vital for our metabolic and immune health. Although the importance of gut
      microbiota in maintaining digestive health has long been believed, its close
      correlation with numerous chronic ailments has recently been noticed, thanks to
      the innovative mechanistic studies on the compositional and functional aspects of
      gut microbial communities using germ-free or humanized animal models. Since a
      myriad of mysteries about the precise structures and functions of gut microbial
      communities in specific health situations still remains to be explicated, the
      emerging field of gut microbiota remains a foremost objective of research for
      microbiologists, immunologists, computational biologists, clinicians, food and
      nutrition experts, etc. Nevertheless, it is only after a comprehensive
      understanding of the structure, density, and function of the gut microbiota that
      the new therapeutic targets could be captured and utilized for a healthier gut as
      well as improved overall well-being. 

PMID- 25767800
TI  - Social participation of diabetes and ex-leprosy patients in the Netherlands and
      patient preference for combined self-care groups.
AB  - INTRODUCTION: Earlier, we showed that neuropathic complications limit social
      participation of ex-leprosy patients, even in a non-endemic leprosy setting like
      the Netherlands. Self-care groups for ex-leprosy patients can strengthen self
      worth of participants, prevent further handicap, and enable the exchange of
      coping strategies. For non-endemic leprosy settings with a very low rate of
      leprosy patients, a self-care group exclusively for (ex)leprosy patients is not
      likely to be feasible. A combined group with patients facing comparable morbidity
      would be more efficient than disease-specific self-care groups. Here, we studied
      the comparability in social constraints of diabetic patients and ex-leprosy
      patients. Moreover, we investigated if combined self-care groups for ex-leprosy
      patients and diabetic patients would be desirable and acceptable for possible
      participants. METHODS: Social participation was studied based on in-depth
      interviews and Participation Scale information collected from 41 diabetic
      patients and compared with the data of 31 ex-leprosy patients from a prior study.
      Moreover, we made an inventory of potential strengths and limitations and
      attitudes toward combined self-care groups for diabetic patients with neuropathy.
      RESULTS: The following themes emerged among diabetic patients: disease
      confrontation, dependency, conflict with partner or relatives, feelings of
      inferiority, stigma, abandoning social activities, fear of the future, lack of
      information, and hiding the disease. These themes were very similar to those
      voiced by the previously interviewed ex-leprosy patients. The latter more often
      mentioned stigma and disease ignorance among Dutch health care workers. Whereas
      ex-leprosy patients perceived stigma on multiple fronts, diabetic patients only
      mentioned feeling inferior. Diabetic patients experienced some form of
      participation restriction in 39% of the cases as opposed to 71% of the ex-leprosy
      patients. Diabetic patients did acknowledge the comparability with leprosy as far
      as their neuropathic complaints concerned. Yet only 17% showed interest in
      combined self-care groups. The majority preferred disease-specific self-care
      groups only focused on diabetic patients. This might have been caused partly by
      the perception that a self-care group is yet another disease-related demand on
      their time, rather than an opportunity to become less dependent on health care
      services. CONCLUSION: The physical complications and social problems in ex
      leprosy and diabetic patients with neuropathy are similar. Both groups show
      social participation limitations, yet in contrast to diabetic patients, ex
      leprosy patients perceive stigma in more domains in life. Despite the fact that
      diabetic patients preferred disease-specific, homogeneous self-care groups, we
      believe that the option of combined groups with ex-leprosy patients and possibly
      even other people needing chronic wound care is a promising strategy. Therefore,
      further research is warranted into the acceptance and impact of self-care groups
      as a strategy to reduce social constraints by diseases causing neuropathy.

PMID- 25767801
TI  - Use of recombinant human soluble thrombomodulin in patients with sepsis-induced
      disseminated intravascular coagulation after intestinal perforation.
AB  - BACKGROUND: Anticoagulant therapy has been evaluated with respect to its
      potential usefulness in reducing the high mortality rates associated with severe
      sepsis, including sepsis-induced disseminated intravascular coagulation (DIC)
      after intestinal perforation. We examined the hypothesis that recombinant human
      soluble thrombomodulin (rhTM) is effective in the treatment of patients with
      septic shock with sepsis-induced DIC after laparotomy for intestinal perforation.
      METHODS: We performed propensity-score and instrumental variable analyses of the
      Japanese Diagnosis Procedure Combination in-patient database, a nationwide
      administrative database. The main outcome was 28-day in-hospital all-cause
      mortality. RESULTS: We categorized eligible patients (n = 2202) from 622
      hospitals into the rhTM group (n = 726) and control group (n = 1476). Propensity
      score matching created 621 matched pairs of patients with and without rhTM. There
      was neither significant difference in 28-day mortality between the two groups in
      the unmatched analysis (rhTM vs. control, 25.3 vs. 23.4%, respectively;
      difference, 1.9%; 95% CI, -1.9 to 5.7) nor in the propensity-score-matched
      analysis (rhTM vs. control, 26.1 vs. 24.8%, respectively; difference, 1.3%; 95%
      CI, -3.6 to 6.1). The logistic analysis showed no significant association between
      the use of rhTM and the mortality in propensity-score-matched patients (OR, 1.1;
      95% CI, 0.82-1.4). The instrumental variable analyses, using the hospital rhTM
      prescribing proportion as the variable, found that receipt of rhTM was not
      associated with the reduction in the mortality (risk difference, -6.7%; 95% CI, 
      16.4 to 3.0). CONCLUSION: We found no association between administration of rhTM
      and 28-day mortality in mechanically ventilated patients with septic shock and
      concurrent DIC after intestinal perforation.

PMID- 25767802
TI  - Preeclampsia - will orphan drug status facilitate innovative biological
      therapies?
AB  - It is generally accepted that the development of novel therapies to treat
      pregnancy-related disorders, such as preeclampsia, is hampered by the paucity of
      research funding. Hence, it is with great interest to become aware of at least
      three novel therapeutic approaches for the treatment of this disorder: exploiting
      either the anticoagulant activity of antithrombin, the free radical scavenging
      activity of alpha-1-microglobulin, or the regenerative capacity of placenta
      derived mesenchymal stem cells. As these projects are being carried out by small
      biotech enterprises, the question arises of how they are able to fund such
      undertakings. A novel strategy adopted by two of these companies is that they
      successfully petitioned US and EU agencies in order that preeclampsia is accepted
      in the register of rare or orphan diseases. This provides a number of benefits
      including market exclusivity, assistance with clinical trials, and dedicated
      funding schemes. Other strategies to supplement meager research funds, especially
      to test novel approaches, could be crowdfunding, a venture that relies on
      intimate interaction with advocacy groups. In other words, preeclampsia meets
      Facebook. Perhaps similar strategies can be adopted to examine novel therapies
      targeting either the imbalance in pro- or anti-angiogenic growth factors,
      complement activation, reduced levels of placenta protein 13, or excessive
      neutrophil activation evident in preeclampsia. 

PMID- 25767803
TI  - Cellular responses evoked by different surface characteristics of intraosseous
      titanium implants.
AB  - The properties of biomaterials, including their surface microstructural
      topography and their surface chemistry or surface energy/wettability, affect
      cellular responses such as cell adhesion, proliferation, and migration. The
      nanotopography of moderately rough implant surfaces enhances the production of
      biological mediators in the peri-implant microenvironment with consequent
      recruitment of differentiating osteogenic cells to the implant surface and
      stimulates osteogenic maturation. Implant surfaces with moderately rough
      topography and with high surface energy promote osteogenesis, increase the ratio
      of bone-to-implant contact, and increase the bonding strength of the bone to the
      implant at the interface. Certain features of implant surface chemistry are also
      important in enhancing peri-implant bone wound healing. It is the purpose of this
      paper to review some of the more important features of titanium implant surfaces
      which have an impact on osseointegration. 

PMID- 25767804
TI  - Analysis for clinical effect of virtual windowing and poking reduction treatment
      for Schatzker III tibial plateau fracture based on 3D CT data.
AB  - OBJECTIVE: To explore the applications of preoperative planning and virtual
      surgery including surgical windowing and elevating reduction and to determine the
      clinical effects of this technology on the treatment of Schatzker type III tibial
      plateau fractures. METHODS: 32 patients with Schatzker type III tibial plateau
      fractures were randomised upon their admission to the hospital using a sealed
      envelope method. Fourteen were treated with preoperative virtual design and
      assisted operation (virtual group) and 18 with direct open reduction and internal
      fixation (control group). RESULTS: All patients achieved primary incision
      healing. Compared with control group, virtual groups showed significant
      advantages in operative time, incision length, and blood loss (P < 0.001). The
      virtual surgery was consistent with the actual surgery. CONCLUSION: The virtual
      group was better than control group in the treatment of tibial plateau fractures
      of Schatzker type III, due to shorter operative time, smaller incision length,
      and lower blood loss. The reconstructed 3D fracture model could be used to
      preoperatively determine the surgical windowing and elevating reduction method
      and simulate the operation for Schatzker type III tibial plateau fractures.

PMID- 25767805
TI  - Determination of the in vitro and in vivo antimicrobial activity on salivary
      Streptococci and Lactobacilli and chemical characterisation of the phenolic
      content of a Plantago lanceolata infusion.
AB  - Introduction. Plant extracts may be suitable alternative treatments for caries.
      Aims. To investigate the in vitro and in vivo antimicrobial effects of Plantago
      lanceolata herbal tea (from flowers and leaves) on cariogenic bacteria and to
      identify the major constituents of P. lanceolata plant. Materials and Methods.
      The MIC and MBC against cariogenic bacteria were determined for P. lanceolata
      tea. Subsequently, a controlled random clinical study was conducted. Group A was
      instructed to rinse with a P. lanceolata mouth rinse, and Group B received a
      placebo mouth rinse for seven days. The salivary colonisation by streptococci and
      lactobacilli was investigated prior to treatment and on the fourth and seventh
      days. Finally, the P. lanceolata tea was analysed for its polyphenolic content,
      and major phenolics were identified. Results and Discussion. P. lanceolata teas
      demonstrate good in vitro antimicrobial activity. The in vivo test showed that
      Group A subjects presented a significant decrease in streptococci compared to
      Group B. The phytochemical analysis revealed that flavonoids, coumarins, lipids,
      cinnamic acids, lignans, and phenolic compounds are present in P. lanceolata
      infusions. Conclusions. P. lanceolata extract could represent a natural
      anticariogenic agent via an antimicrobial effect and might be useful as an
      ancillary measure to control the proliferation of cariogenic flora. 

PMID- 25767806
TI  - Characterizing facial skin ageing in humans: disentangling extrinsic from
      intrinsic biological phenomena.
AB  - Facial skin ageing is caused by intrinsic and extrinsic mechanisms. Intrinsic
      ageing is highly related to chronological age. Age related skin changes can be
      measured using clinical and biophysical methods. The aim of this study was to
      evaluate whether and how clinical characteristics and biophysical parameters are
      associated with each other with and without adjustment for chronological age.
      Twenty-four female subjects of three age groups were enrolled. Clinical
      assessments (global facial skin ageing, wrinkling, and sagging), and biophysical
      measurements (roughness, colour, skin elasticity, and barrier function) were
      conducted at both upper cheeks. Pearson's correlations and linear regression
      models adjusted for age were calculated. Most of the measured parameters were
      correlated with chronological age (e.g., association with wrinkle score, r =
      0.901) and with each other (e.g., residual skin deformation and wrinkle score, r
      = 0.606). After statistical adjustment for age, only few associations remained
      (e.g., mean roughness (R z ) and luminance (L (*)),  beta = -0.507, R (2) =
      0.377). Chronological age as surrogate marker for intrinsic ageing has the most
      important influence on most facial skin ageing signs. Changes in skin elasticity,
      wrinkling, sagging, and yellowness seem to be caused by additional extrinsic
      ageing. 

PMID- 25767807
TI  - Aquaporin 5 expression in mouse mammary gland cells is not driven by promoter
      methylation.
AB  - Several studies have revealed that aquaporins play a role in tumor progression
      and invasion. In breast carcinomas, high levels of aquaporin 5 (AQP5), a membrane
      protein involved in water transport, have been linked to increased cell
      proliferation and migration, thus facilitating tumor progression. Despite the
      potential role of AQP5 in mammary oncogenesis, the mechanisms controlling mammary
      AQP5 expression are poorly understood. In other tissues, AQP5 expression has been
      correlated with its promoter methylation, yet, very little is known about AQP5
      promoter methylation in the mammary gland. In this work, we used the mouse
      mammary gland cell line EpH4, in which we controlled AQP5 expression via the
      steroid hormone dexamethasone (Dex) to further investigate mechanisms regulating
      AQP5 expression. In this system, we observed a rapid drop of AQP5 mRNA levels
      with a delay of several hours in AQP5 protein, suggesting transcriptional control
      of AQP5 levels. Yet, AQP5 expression was independent of its promoter methylation,
      or to the presence of negative glucocorticoid receptor elements (nGREs) in its
      imminent promoter region, but was rather influenced by the cell proliferative
      state or cell density. We conclude that AQP5 promoter methylation is not a
      universal mechanism for AQP5 regulation and varies on cell and tissue type. 

PMID- 25767808
TI  - Quadruple burden of HIV/AIDS, tuberculosis, chronic intestinal parasitoses, and
      multiple micronutrient deficiency in ethiopia: a summary of available findings.
AB  - Human immunodeficiency virus (HIV), tuberculosis (TB), and helminthic infections
      are among the commonest public health problems in the sub-Saharan African
      countries like Ethiopia. Multiple micronutrient deficiencies also known as the
      "hidden hunger" are common in people living in these countries either playing a
      role in their pathogenesis or as consequences. This results in a vicious cycle of
      multiple micronutrient deficiencies and infection/disease progression. As
      infection is profoundly associated with nutritional status resulting from
      decreased nutrient intake, decreased nutrient absorption, and nutrient losses,
      micronutrient deficiencies affect immune system and impact infection and diseases
      progression. As a result, micronutrients, immunity, and infection are
      interrelated. The goal of this review is therefore to provide a summary of
      available findings regarding the "quadruple burden trouble" of HIV, TB,
      intestinal parasitic infections, and multiple micronutrient deficiencies to
      describe immune-modulating effects related to disorders. 

PMID- 25767809
TI  - Protection against multiple subtypes of influenza viruses by virus-like particle
      vaccines based on a hemagglutinin conserved epitope.
AB  - We selected the conserved sequence in the stalk region of influenza virus
      hemagglutinin (HA) trimmer, the long alpha helix (LAH), as the vaccine candidate
      sequence, and inserted it into the major immunodominant region (MIR) of hepatitis
      B virus core protein (HBc), and, by using the E. coli expression system, we
      prepared a recombinant protein vaccine LAH-HBc in the form of virus-like
      particles (VLP). Intranasal immunization of mice with this LAH-HBc VLP plus
      cholera toxin B subunit with 0.2% of cholera toxin (CTB(*)) adjuvant could
      effectively elicit humoral and cellular immune responses and protect mice against
      a lethal challenge of homologous influenza viruses (A/Puerto Rico/8/1934 (PR8)
      (H1N1)). In addition, passage of the immune sera containing specific antibodies
      to naive mice rendered them resistant against a lethal homologous challenge.
      Immunization with LAH-HBc VLP vaccine plus CTB(*) adjuvant could also fully
      protect mice against a lethal challenge of the 2009 pandemic H1N1 influenza virus
      or the avian H9N2 virus and could partially protect mice against a lethal
      challenge of the avian H5N1 influenza virus. This study demonstrated that the LAH
      HBc VLP vaccine based on a conserved sequence of the HA trimmer stalk region is a
      promising candidate vaccine for developing a universal influenza vaccine against
      multiple influenza viruses infections. 

PMID- 25767810
TI  - Fan-shaped complete block on helical tomotherapy for esophageal cancer: a phantom
      study.
AB  - Radiation pneumonitis (RP) is a common complication for radiotherapy of
      esophageal cancer and is associated with the low dose irradiated lung volume.
      This study aims to reduce the mean lung dose (MLD) and the relative lung volume
      at 20 Gy (V 20) and at low dose region using various designs of the fan-shaped
      complete block (FSCB) in helical tomotherapy. Hypothetical esophageal tumor was
      delineated on an anthropomorphic phantom. The FSCB was defined as the fan-shaped
      radiation restricted area located in both lungs. Seven treatment plans were
      performed with nonblock design and FSCB with different fan angles, that is, from
      90 degrees  to 140 degrees , with increment of 10 degrees . The homogeneous
      index, conformation number, MLD, and the relative lung volume receiving more than
      5, 10, 15, and 20 Gy (V 5, V 10, V 15, and V 20) were determined for each
      treatment scheme. There was a substantial reduction in the MLD, V 5, V 10, V 15,
      and V 20 when using different types of FSCB as compared to the nonblock design.
      The reduction of V 20, V 15, V 10, and V 5 was 6.3%-8.6%, 16%-23%, 42%-57%, and
      42%-66% for FSCB 90 degrees -140 degrees , respectively. The use of FSCB in
      helical tomotherapy is a promising method to reduce the MLD, V 20, and relative
      lung volume in low dose region, especially in V 5 and V 10 for esophageal cancer.

PMID- 25767812
TI  - Fruit and vegetable consumption and the related factors among Iranian female high
      school students, Gochan, Iran, 2013.

PMID- 25767811
TI  - Synergistic activations of REG I alpha and REG I beta promoters by IL-6 and
      Glucocorticoids through JAK/STAT pathway in human pancreatic beta cells.
AB  - Reg (Regenerating gene) gene was originally isolated from rat regenerating islets
      and its encoding protein was revealed as an autocrine/paracrine growth factor for
      beta cells. Rat Reg gene is activated in inflammatory conditions for beta cell
      regeneration. In human, although five functional REG family genes (REG Ialpha,
      REG Ibeta, REG III, HIP/PAP, and REG IV) were isolated, their expressions in beta
      cells under inflammatory conditions remained unclear. In this study, we found
      that combined addition of IL-6 and dexamethasone (Dx) induced REG Ialpha and REG
      Ibeta expression in human 1.1B4 beta cells. Promoter assay revealed that a signal
      transducer and activator of transcription- (STAT-) binding site in each promoter
      of REG Ialpha (TGCCGGGAA) and REG Ibeta (TGCCAGGAA) was essential for the IL-6+Dx
      induced promoter activation. A Janus kinase 2 (JAK2) inhibitor significantly
      inhibited the IL-6+Dx-induced REG Ialpha and REG Ibeta transcription.
      Electrophoretic mobility shift assay and chromatin immunoprecipitation revealed
      that IL-6+Dx stimulation increased STAT3 binding to the REG Ialpha promoter.
      Furthermore, small interfering RNA-mediated targeting of STAT3 blocked the IL
      6+Dx-induced expression of REG Ialpha and REG Ibeta. These results indicate that
      the expression of REG Ialpha and REG Ibeta should be upregulated in human beta
      cells under inflammatory conditions through the JAK/STAT pathway. 

PMID- 25767813
TI  - Learning theories application in nursing education.
AB  - Learning theories are the main guide for educational systems planning in the
      classroom and clinical training included in nursing. The teachers by knowing the
      general principles of these theories can use their knowledge more effectively
      according to various learning situations. In this study, Eric, Medline, and
      Cochrane databases were used for articles in English and for the Persian
      literature, Magiran, Iran doc, Iran medex, and Sid databases were used with the
      help of keywords including social cognitive learning, learning theory, behavioral
      theory, cognitive theory, constructive theory, and nursing education. The search
      period was considered from 1990 to 2012. Some related books were also studied
      about each method, its original vision, the founders, practical application of
      the training theory, especially training of nursing and its strengths and
      weaknesses. Behaviorists believe that learning is a change in an observable
      behavior and it happens when the communication occurs between the two events, a
      stimulus and a response. Among the applications of this approach is the influence
      on the learner's emotional reactions. Among the theories of this approach,
      Thorndike and Skinner works are subject to review and critique. Cognitive
      psychologists unlike the behaviorists believe that learning is an internal
      process objective and they focus on thinking, understanding, organizing, and
      consciousness. Fundamentalists believe that learners should be equipped with the
      skills of inquiry and problem solving in order to learn by the discovery and
      process of information. Among this group, we will pay attention to analyze
      Wertheimer, Brunner, Ausubel theories, Ganyeh information processing model, in
      addition to its applications in nursing education. Humanists in learning pay
      attention to the feelings and experiences. Carl Rogers support the retention of
      learning-centered approach and he is believed to a semantic continuum. At the
      other end of the continuum, experiential learning is located with the meaning and
      meaningful. It applies the minds and feelings of the person. From this group, the
      main focus will be on the works of Rogers and Novels. Finally, it could be
      concluded that the usage of any of these theoriesin its place would be desired
      and useful. 

PMID- 25767814
TI  - Investigating the relationship between the demographic variables associated with
      suicide in different seasons, among suicidal people in the Shahid Mohammadi
      Hospital, Bandar Abass, Iran.
AB  - INTRODUCTION: Suicide is committed by a person himself or herself and whether
      conscious or semiconscious it is aimed to end one's life. This action is not
      committed inadvertently or incongruously. However, it could be related to one's
      unmet needs and feelings of despair. Studies on the prevalence of suicide are
      related to environmental and seasonal circumstances. As there are diverse
      populations in Bandar Abbas of different races due to its geographical position,
      and as its weather condition is different from the other parts of country there
      is no study with this regard. Hence, the aim of this research is to investigate
      the correlations between and among demographical variables and suicide in
      different seasons of the year. MATERIALS AND METHODS: This study is a cross
      sectional one. Participants included 80 persons who had attempted suicide and
      were hospitalized within 2011 in the Ebnesina Hospital of Bandar Abases, Iran.
      The variables under investigation are the suicidal patients' demographic
      characteristics, where, when, and how the person had committed suicide. All of
      these data were available in their profiles. These data were analyzed by using
      the SSPS software. RESULTS: The results showed that 45% of the suicidal people
      were the young and adolescent. Also, 75.5% of these people were single and 22.5%
      of them were married. Most suicides occurred in summer, which makes up 41.3% of
      all the suicidal people. On the other hand 11.3% of the suicides were committed
      successfully and 88.7% of them had been unsuccessful; 42.5% of suicidal people
      had used drugs and 38.8% of them had used pesticides to commit suicide - 78.8% of
      these patients had psychotic disorders and 12.5% of them suffered from mental
      disorders such as schizophrenia. Furthermore, a significant relationship was
      found between seasons in which suicide was committed, marital status, age, mental
      illness, and educational and occupational characteristics of suicidal patients.
      CONCLUSION: This study showed that the most vulnerable people committing suicide
      were from among the young and adolescent. Singles had attempted suicide more than
      the married. Most of suicide attempters had used drugs to commit suicide.
      Generally, in the current study, some variables including season, marital status,
      age, history of mental illnesses, and educational and occupational variables were
      all associated with committing suicide.

PMID- 25767815
TI  - The effect of preventive educational program in cigarette smoking: Extended
      Parallel Process Model.
AB  - BACKGROUND: Cigarette smoking is one of the preventable causes of diseases and
      deaths. The most important preventive measure is technique to resist against peer
      pressure. Any educational program should design with an emphasis upon theories of
      behavioral change and based on effective educational program. To investigate the
      interventions through educational program in prevention of cigarette smoking,
      this paper has used the Extended Parallel Process Model (EPPM). MATERIALS AND
      METHODS: This study is a quasi-experimental study. Two middle schools were
      randomly selected from male students in Shiraz. Therefore, we randomly selected
      120 students for the experimental group and 120 students for the control group.
      After diagnostic evaluation, educational interventions on the consequences of
      smoking and preventive skills were applied. RESULTS: Our results indicated that
      there was a significant difference between students in the control and
      experimental groups in the means of perceived susceptibility (P < 0.000, t =
      6.84), perceived severity (P < 0.000, t = -11.46), perceived response efficacy (P
      < 0.000, t = -7.07), perceived self-efficacy (P < 0.000, t = -11.64), and
      preventive behavior (P < 0.000, t = -24.36). CONCLUSIONS: EPPM along with
      educating skills necessary to resist against peer pressure had significant level
      of efficiency in improving preventive behavior of cigarette smoking among
      adolescents. However, this study recommends further studies on ways of increasing
      perceived susceptibility in cigarette smoking among adolescents.

PMID- 25767816
TI  - Analysis of the quality of hospital information systems in Isfahan teaching
      hospitals based on the DeLone and McLean model.
AB  - BACKGROUND: Quality is one of the most important criteria for the success of an
      information system, which refers to its desirable features of the processing
      system itself. The aim of this study was the analysis of system quality of
      hospital information systems (HIS) in teaching hospitals of Isfahan based on the
      DeLone and McLean model. MATERIALS AND METHODS: This research was an applied and
      analytical-descriptive study. It was performed in teaching hospitals of Isfahan
      in 2010. The research population consisted of the HIS's users, system designers
      and hospital information technology (IT) authorities who were selected by random
      sampling method from users' group (n = 228), and system designers and IT
      authorities (n = 52) using census method. The data collection tool was two
      researcher-designed questionnaires. Questionnaires' reliability was estimated by
      using Cronbach's alpha was calculated. It was 97.1% for the system designers and
      IT authorities' questionnaire and 92.3% for system users' questionnaire. RESULTS:
      Findings showed that the mean of system quality score in a variety of HIS and
      among different hospitals was significantly different and not the same (P value
      >= 0.05). In general, Kosar (new version) system and Rahavard Rayaneh system have
      dedicated the highest and the lowest mean scores to themselves. The system
      quality criterion overall mean was 59.6% for different HIS and 57.5% among
      different hospitals respectively. CONCLUSION: According to the results of the
      research, it can be stated that based on the applied model, the investigated
      systems were relatively desirable in terms of quality. Thus, in order to achieve
      a good optimal condition, it is necessary to pay particular attention to the
      improving factors of system quality, type of activity, type of specialty and
      hospital ownership type.

PMID- 25767818
TI  - Need assessment of staffs' welfare services at tehran university of medical
      sciences: a cross-sectional study.
AB  - BACKGROUND: Reviewing the human resources management literature shows an absence
      of attention given to the employee's benefits. Taking a look at functions of the
      Tehran University of Medical Sciences' wellbeing services system, it uncovers a
      gap between employees' real needs and what is delivered to meet their needs. So
      it requires an improved comprehensive system for delivering wellbeing services
      (financial, insurance, health care services, educational and training services,
      etc). Wellbeing need assessment can helps planners to identify vital needs of
      employee and response to them effectively. Moreover it can be used to evaluate
      the effectiveness of the current services which are delivered. Thus, the aim of
      this study is to assess wellbeing services of staffs working in TUMS to (1)
      evaluate the satisfactory rate of services which are delivered, and (2) exploring
      those wellbeing needs which were not fulfilled by the organization. MATERIAL AND
      METHODS: Being a cross-sectional and analytic-descriptive survey including 98
      responding participants, it is conducted by a questionnaire collecting employees'
      demographic information, their satisfactory rate of the implemented services, and
      determines unfulfilled wellbeing needs which were not already covered. RESULT:
      Results indicated that services related to financial, educational, non-financial,
      insurance, occupational health and tourism/recreational services were the most
      satisfactory services successively. 'Staff's unwillingness to receive services'
      and 'poor announcement' (unawareness on the wellbeing services),' were found to
      be the most frequent reasons for not receiving the existing wellbeing services.
      CONCLUSION: To increase the satisfaction rate and responsiveness to the real
      needs of the staff, the current delivery system of wellbeing services in the TUMS
      should be redesigned by defining new wellbeing packages.

PMID- 25767817
TI  - Women's needs and expectations during normal labor and delivery.
AB  - BACKGROUND: Pregnancy and birth are unique processes for women. Women and
      families hold different expectation during childbearing based on their knowledge,
      experiences, belief systems, culture, and social and family backgrounds. These
      differences should be understood and respected, and care is adapted and organized
      to meet the individualized needs of women and families. The purpose of this study
      was to explore Iranian parturient needs, values and preferences during normal
      labor and delivery. MATERIALS AND METHODS: An exploratory qualitative study was
      used. Twenty-four parturient women from three governmental medical training
      centers in Isfahan, Iran were recruited using purposive sampling. Participants
      were recruited to low-risk women after they had given birth, but before they were
      discharged from hospital. Data were collected through semi-structured in-depth
      interviews, informal observations and field notes. Interviews were transcribed
      verbatim and analyzed by the conventional content analysis according to Graneheim
      and Lundman approach. RESULTS: Women's needs and expectations fell into seven
      main categories: Physiological, psychological, informational, social and
      relational, esteem, security and medical needs. All of the key needs in these
      data relates to a fundamental need, named "sense of control and empowerment in
      childbirth." CONCLUSION: Knowing a woman's needs, values, preferences and
      expectations during normal labor and delivery assists healthcare professionals
      especially midwives in providing high-quality care to parturient women.

PMID- 25767819
TI  - Preconception care in diabetic women.
AB  - INTRODUCTION: Diabetes is increasingly becoming prevalent worldwide. Pregnancy
      with diabetes is prone to maternal and fetal complications. Preconception care
      (PCC) is an important factor in alleviating gestational complications in those
      women who suffer from diabetes. This study seeks to gain insight into experiences
      of diabetic women and providers about PCC. SUBJECTS AND METHODS: The present
      research was a qualitative research conducted on eight women with diabetes during
      the reproductive age and 15 health care providers of the public and private
      medical centers, which provide health care for women with diabetes in Isfahan
      (Iran), with a qualitative approach. Based on the aims of research, purposive
      sampling was done through semi-structuralized individual interview. Data were
      analyzed using conventional qualitative content analysis method. RESULTS: Data
      analysis revealed three major categories: (1) Health centers weakness in
      providing PCC for diabetic women, (2) lack of a comprehensive PCC plan for
      diabetic women and (3) diabetic women's negligence about having planned
      pregnancy. CONCLUSION: In order to improve diabetic women's health, precise
      training of students, health care providers and patients themselves with respect
      to PCCs should be taken into account. Designing diabetic PCC system is an
      essential factor to succeed in this trend.

PMID- 25767820
TI  - Analysis of some predictive factors of quality of life among type 2 diabetic
      patients.
AB  - INTRODUCTION: Considering the chronic nature of diabetes and its significant
      effect on quality of life of patients, the present study was conducted to
      evaluate predictors of quality of life in these patients in order to facilitate
      planning health promotion intervention programs. MATERIALS AND METHODS: The
      present study was designed as a cross-sectional study on 140 type 2 diabetic
      patients of Om-ol-Banin Diabetes Center of Isfahan. Data collection tool was a
      multidimensional questionnaire including demographic and disease related data (12
      items), the standard scale for diabetes distress (17 items), the standard scale
      for self-efficacy in diabetic patients (8 items), and standard scale for specific
      quality of life of diabetic patients (15 items). Collected data were evaluated by
      SPSS version 11.5 using the Chi-square test, Independent T-test, ANOVA, Pearson
      correlation and multivariate regression analysis. RESULTS: Results showed that
      the quality of life of diabetic patients had a statistically significant
      correlation with diabetes distress variable (P < 0.001) and self-efficacy
      variable (P < 0.001). In this study R(2) (predictive power) was 0.66.
      Multivariate regression model indicated diabetes distress (beta = -0.277, P =
      0.01) and self-efficacy (beta = -0.161, P < 0.001) as variables influencing
      adjusted self-management for other variables. CONCLUSION: The result of the
      present study urges that in planning health promotion interventions in the field
      of diabetes, more attention be paid to self-efficacy and diabetes distress
      variables in order to improve the efficiency and effectiveness of the
      interventions carried out.

PMID- 25767821
TI  - Effect of a supportive-educative program in the math class for stress, anxiety,
      and depression in female students in the third level of junior high school: An
      action research.
AB  - BACKGROUND AND AIM: Students in junior high school, particularly in the third
      level, are prone to a variety of stressors. This in turn might lead to stress,
      anxiety, depression, and other health-related problems. There are a very limited
      number of action research studies to identify the effect of stress management
      techniques among students. Therefore, a study was conducted to assess the effect
      of a program used in the math class to decrease the student's level of stress,
      anxiety, and depression. MATERIAL AND METHODS: This was an action research study,
      which was conducted in region three of the Education and Training Office of
      Isfahan, in the year 2012. Fifty-one students in a junior high school were
      selected and underwent a comprehensive stress management program. This program
      was prepared in collaboration with the students, their parents, teachers, and
      managers of the school, and was implemented approximately during a four-month
      period. The student's stress, anxiety, and depression were measured before and
      after the program using the DASS-21 questionnaire. FINDINGS: The t-test
      identified that the mean scores of stress, anxiety, and depression after the
      intervention were significantly lower than the corresponding scores before the
      program. One-way analysis of variance (ANOVA) also showed that the students from
      the veterans (Janbaz) families had higher levels of stress compared to their
      classmates, who belonged to the non-veteran families (P< 0.05). RESULTS:
      Education and implementation of stress management techniques including cognitive
      and behavioral interventions along with active and collaborative methods of
      learning in the math class might be useful both inside and outside the class, for
      better management of stress and other health-related problems of students.

PMID- 25767822
TI  - Investigating the prevalence and causes of events leading to falls among the
      elderly hospitalized in Bandar Abbas hospitals.
AB  - BACKGROUND AND PURPOSE OF STUDY: Statistical indices show a growing increase in
      the elderly population around the world and our country. On the one hand, senior
      citizens are more exposed to tragic events than other age groups due to natural
      physiological changes. Falling down, accidents and scalds are among the most
      prevalent deadly events in this age group. Environmental security is vital in
      maintaining the elderly's health. Therefore, the present research was conducted
      seeking to determine the prevalence and causes of falls among the elderly
      hospitalized in Bandar Abbas hospitals. METHODS AND MATERIALS: The present
      research is of a descriptive, cross-sectional type. Research population is
      comprised of all the elderly patients in Bandar Abbas hospitals. The sample
      included 300 individuals who were selected according to convenience sampling
      method till the sample was saturated. The instrument used was a questionnaire and
      the data were also gathered through interviews. The collected data were later
      analyzed by SPSS version 16. To analyze the data, descriptive statistics
      (frequency and percentage) were used along with the Chi-squared test. The
      significance level was set at P < 0.05. RESULTS: From among the 300 subjects,
      47.3% had experienced falls since the age of 60. In 22 of cases, it had led to
      injury and they were obliged to visit a doctor. The results of this research
      revealed that the causes of falls among the elderly were respectively: 43.33% of
      unbalance, 12.3% of poor eyesight, 11.66% of non-existing handles or fences, 12%
      of slippery ground, 2.66% of insufficient lightning, 8.66% of unbalance and poor
      eyesight and 9.33% of other reasons. As the results revealed, a correlation
      existed between falls and educational level (P < 0.025). Moreover, a significant
      correlation was found between sex and falls (P < 0.011). A similar significant
      correlation was also observed between the place of residence and falling down (P
      < 0.045). CONCLUSION: According to the research results, planning to prevent
      events and traumas among the elderly and securing their residential environment
      is of an essential significance.

PMID- 25767823
TI  - The PBDE metabolite 6-OH-BDE 47 affects melanin pigmentation and THRbeta MRNA
      expression in the eye of zebrafish embryos.
AB  - Polybrominated diphenyl ethers and their hydroxyl-metabolites (OH-BDEs) are
      commonly detected contaminants in human serum in the US population. They are also
      considered to be endocrine disruptors, and are specifically known to affect
      thyroid hormone regulation. In this study, we investigated and compared the
      effects of a PBDE and its OH-BDE metabolite on developmental pathways regulated
      by thyroid hormones using zebrafish as a model. Exposure to 6-OHBDE 47 (10-100
      nM), but not BDE 47 (1-50 MUM), led to decreased melanin pigmentation and
      increased apoptosis in the retina of zebrafish embryos in a concentration
      dependent manner in short-term exposures (4 - 30 hours). Six-OH-BDE 47 exposure
      also significantly decreased thyroid hormone receptor beta (THRbeta) mRNA
      expression, which was confirmed using both RT-PCR and in situ hybridization
      (whole mount and paraffin- section). Interestingly, exposure to the native
      thyroid hormone, triiodothyronine (T3) also led to similar responses: decreased
      THRbeta mRNA expression, decreased melanin pigmentation and increased apoptosis,
      suggesting that 6-OH-BDE 47 may be acting as a T3 mimic. To further investigate
      short-term effects that may be regulated by THRbeta, experiments using a
      morpholino gene knock down and THRbeta mRNA over expression were conducted. Knock
      down of THRbeta led to decreases in melanin pigmentation and increases in
      apoptotic cells in the eye of zebrafish embryos, similar to exposure to T3 and 6
      OH-BDE 47, but THRbeta mRNA overexpression rescued these effects. Histological
      analysis of eyes at 22 hpf from each group revealed that exposure to T3 or to 6
      OH-BDE 47 was associated with a decrease of melanin and diminished proliferation
      of cells in layers of retina near the choroid. This study suggests that 6-OH-BDE
      47 disrupts the activity of THRbeta in early life stages of zebrafish, and
      warrants further studies on effects in developing humans.

PMID- 25767824
TI  - Ultrastructural analysis of Leishmania infantum chagasi promastigotes forms
      treated in vitro with usnic acid.
AB  - Leishmaniasis is considered by the World Health Organization as one of the
      infectious parasitic diseases endemic of great relevance and a global public
      health problem. Pentavalent antimonials used for treatment of this disease are
      limited and new phytochemicals emerge as an alternative to existing treatments,
      due to the low toxicity and cost reduction. Usnic acid is uniquely found in
      lichens and is especially abundant in genera such as Alectoria, Cladonia,
      Evernia, Lecanora, Ramalina, and Usnea. Usnic acid has been shown to exhibit
      antiviral, antiprotozoal, antiproliferative, anti-inflammatory, and analgesic
      activity. The aim of this study was to evaluate the antileishmanial activity of
      usnic acid on Leishmania infantum chagasi promastigotes and the occurrence of
      drug-induced ultrastructural damage in the parasite. Usnic acid was effective
      against the promastigote forms (IC50=18.30+/-2.00 ug/mL). Structural and
      ultrastructural aspects of parasite were analyzed. Morphological alterations were
      observed as blebs in cell membrane and shapes given off, increasing the number of
      cytoplasmic vacuoles, and cellular and mitochondrial swelling, with loss of cell
      polarity. We concluded that the usnic acid presented antileishmanial activity
      against promastigote forms of Leishmania infantum chagasi and structural and
      ultrastructural analysis reinforces its cytotoxicity. Further, in vitro studies
      are warranted to further evaluate this potential.

PMID- 25767825
TI  - Effects of storage time on total protein and globulin concentrations in bovine
      fresh frozen plasma obtained for transfusion.
AB  - To evaluate the effects of storage conditions on total protein (TP) and globulin
      fractions in fresh frozen bovine plasma units prepared and stored for
      transfusion, TP and globulin fractions were evaluated in fresh plasma and at 1
      month and 6 and 12 months after blood collection in plasma stored at -20 degrees
      C. Significant differences in concentrations were found in the median
      concentration of total protein (P=0.0336), between 0 months and 1 month
      (P=0.0108), 0 and 6 months (P=0.0023), and 0 and 12 months (P=0.0027), in mean
      concentration (g/dL) of albumin (P=0.0394), between 0 months and 1 month
      (P=0.0131), 0 and 6 months (P=0.0035), and 0 and 12 months (P=0.0038), and beta-2
      fraction (P=0.0401), between 0 and 6 months (P=0.0401) and 0 and 12 months
      (P=0.0230). This study suggests that total gamma globulin concentration in bovine
      frozen plasma is stable for 12 months at -20 degrees C. Total protein, ALB, and
      beta-2 fraction have significantly different concentrations (g/dL) when compared
      to prestorage. This study has shown IgG protein fraction stability in bovine
      fresh frozen plasma collected for transfusion; therefore, bovine fresh frozen
      plasma seems to be suitable for the treatment of hypogammaglobulinemia (failure
      of passive transfer) in calves when stored for 12 months at -20 degrees C.

PMID- 25767826
TI  - Geometric data perturbation-based personal health record transactions in cloud
      computing.
AB  - Cloud computing is a new delivery model for information technology services and
      it typically involves the provision of dynamically scalable and often virtualized
      resources over the Internet. However, cloud computing raises concerns on how
      cloud service providers, user organizations, and governments should handle such
      information and interactions. Personal health records represent an emerging
      patient-centric model for health information exchange, and they are outsourced
      for storage by third parties, such as cloud providers. With these records, it is
      necessary for each patient to encrypt their own personal health data before
      uploading them to cloud servers. Current techniques for encryption primarily rely
      on conventional cryptographic approaches. However, key management issues remain
      largely unsolved with these cryptographic-based encryption techniques. We propose
      that personal health record transactions be managed using geometric data
      perturbation in cloud computing. In our proposed scheme, the personal health
      record database is perturbed using geometric data perturbation and outsourced to
      the Amazon EC2 cloud. 

PMID- 25767827
TI  - Stabilization of a highly porous metal-organic framework utilizing a carborane
      based linker.
AB  - The first tritopic carborane-based linker, H3BCA (C15B24O6H30), based on closo
      1,10-C2B8H10, has been synthesized and incorporated into a metal-organic
      framework (MOF), NU-700 (Cu3(BCA)2). In contrast to the analogous MOF-143, NU-700
      can be activated with retention of porosity, yielding a BET surface area of 1870
      m(2) g(-1).

PMID- 25767828
TI  - Towards neat methanol operation of direct methanol fuel cells: a novel self
      assembled proton exchange membrane.
AB  - We report here a novel proton exchange membrane with remarkably high methanol
      permeation resistivity and excellent proton conductivity enabled by carefully
      designed self-assembled ionic conductive channels. A direct methanol fuel cell
      utilizing the membrane performs well with a 20 M methanol solution, very close to
      the concentration of neat methanol. 

PMID- 25767829
TI  - The dielectric study of insulin-loaded reverse hexagonal (H(II)) liquid crystals.
AB  - The dielectric behavior of the insulin-loaded HII mesophase (containing GMO-TAG
      water-glycerol-insulin) was studied using two empty reference systems (GMO-TAG
      water and GMO-TAG-water-glycerol) at a frequency range of 10(-2)-10(6) Hz, and a
      temperature range of 290-333 K. Three clearly defined relaxation processes were
      observed and assigned to the reorientation of GMO polar heads, the tangential
      movement of counterions at the interface, and the movements of TAGs through the
      lipid tail. Upon addition of glycerol, a heterogeneous inner structure was formed
      within the HII cylinders: the water-glycerol core surrounded by a water rigid
      layer. Upon heating, two critical points were detected referring to the
      dehydration of the GMO heads (at 304 K, similar to the water-filled HII system)
      and to energetic modifications (at 316 K), resulting in breaking of the water
      layer allowing on-demand controlled release. Insulin incorporation combined the
      features of both reference HII systems. Yet, unlike the empty HII systems,
      insulin perturbed the GMO-water interface while decreasing the movement of the
      GMO headgroup, and reducing T0 (296 K). No interactions were formed between the
      dipole of each counterion at the interface region and the matrix (the GMO),
      fitting the Debye process. Dynamic behavior was observed, pointing to mobility
      between the hexagonal rods themselves, enabling controlled release from the HII
      carrier. 

PMID- 25767831
TI  - pH-Assisted control over the binding and relocation of an acridine guest between
      a macrocyclic nanocarrier and natural DNA.
AB  - The differential binding affinity of the hydroxypropyl-beta-cyclodextrin
      (HPbetaCD) macrocycle, a drug delivery vehicle, towards the protonated and
      deprotonated forms of the well-known DNA binder and model anticancer drug
      acridine has been exploited as a strategy for dye-drug transportation and pH
      responsive delivery to a natural DNA target. From pH-sensitive changes in the
      ground state absorption and steady-state fluorescence characteristics of the
      studied acridine dye-HPbetaCD-DNA ternary system and strongly supported by
      fluorescence lifetime, fluorescence anisotropy, Job's plots, (1)H NMR and
      circular dichroism results, it is revealed that in a moderately alkaline solution
      (pH ~ 8.5), the dye can be predominantly bound to the HPbetaCD macrocycle and
      when the pH is lowered to a moderately acidic region (pH ~ 4), the dye
      efficiently detaches from the HPbetaCD cavity and almost exclusively binds to
      DNA. In the present study we are thus able to construct a pH-sensitive
      supramolecular assembly where pH acts as a simple stimulus for controlled uptake
      and targeted release of the dye-drug. As pH is an essential and sensitive factor
      in various biological processes, a simple yet reliable pH-sensitive model such as
      is demonstrated here can have promising applications in the host-assisted
      delivery of prodrug to the target sites, such as cancer or tumour
      microenvironments, with an enhanced stability, bioavailability and activity, and
      also in the design of new fluorescent probes, sensors and smart materials for
      applications in nano-science. 

PMID- 25767830
TI  - Orbital entanglement and CASSCF analysis of the Ru-NO bond in a Ruthenium
      nitrosyl complex.
AB  - Complete active space self-consistent field (CASSCF) wavefunctions and an orbital
      entanglement analysis obtained from a density-matrix renormalisation group (DMRG)
      calculation are used to understand the electronic structure, and, in particular,
      the Ru-NO bond of a Ru nitrosyl complex. Based on the configurations and orbital
      occupation numbers obtained for the CASSCF wavefunction and on the orbital
      entropy measurements evaluated for the DMRG wavefunction, we unravel electron
      correlation effects in the Ru coordination sphere of the complex. It is shown
      that Ru-NO pi bonds show static and dynamic correlation, while other Ru-ligand
      bonds feature predominantly dynamic correlation. The presence of static
      correlation requires the use of multiconfigurational methods to describe the Ru
      NO bond. Subsequently, the CASSCF wavefunction is analysed in terms of
      configuration state functions based on localised orbitals. The analysis of the
      wavefunctions in the electronic singlet ground state and the first triplet state
      provides a picture of the Ru-NO moiety beyond the standard representation based
      on formal oxidation states. A distinct description of the Ru and NO fragments is
      advocated. The electron configuration of Ru is an equally weighted superposition
      of Ru(II) and Ru(III) configurations, with the Ru(III) configuration originating
      from charge donation mostly from Cl ligands. However, and contrary to what is
      typically assumed, the electronic configuration of the NO ligand is best
      described as electroneutral. 

PMID- 25767832
TI  - Elucidating the enhancement in optical properties of low band gap polymers by
      tuning the structure of alkyl side chains.
AB  - We carry out a computational study of optical properties of two novel 5,6
      difluorobenzo[c][1,2,5]-thiadiazole-based polymers, PFBT-T20TT and PFBT-T12TT, to
      elucidate the surprisingly superior performance of polymer solar cells based on
      the former, when it differs from the latter only in the alkyl side chains.
      Density Functional Theory (DFT) based geometry optimization at the B3LYP/6-31G(d)
      level reveals differences in internal coordinates, which are important in tuning
      the electronic and optical properties. We further calculate the electronic
      structure at room temperature by employing molecular dynamics (MD) simulations in
      combination with DFT techniques. The energies of the highest occupied molecular
      orbital (HOMO) are found to be in reasonable agreement with the available
      experimental data and the HOMO-lowest unoccupied MO energy gap is found to be
      similar for both the molecules. The electronic density of the HOMO in PFBT-T20TT
      is, however, found to be significantly more delocalized along the backbone, which
      is proposed to be conducive for the formation of charge separated states leading
      to an improved device performance. Furthermore, via fitting the absorption
      spectra calculated with the multi-mode Brownian Oscillator model, we have also
      extracted a weaker exciton-phonon coupling parameter in PFBT-T20TT, consistent
      with the trends revealed via the DFT-MD results. 

PMID- 25767833
TI  - The modification of ferroelectric LiNbO3(0001) surfaces using chromium oxide thin
      films.
AB  - The impact of ferroelectric polarization on the chemical and electronic
      properties of atomically thin layers of non-polar chromium oxide deposited on
      positively and negatively poled LiNbO3(0001) was studied. Chromium(III) oxide
      readily forms on LiNbO3; however, annealing at high temperatures was required to
      maintain well-ordered films as the thickness increased. Prolonged heating at
      these temperatures caused Cr diffusion into the LiNbO3 substrate. Comparing Cr 2p
      X-ray photoelectron spectroscopy (XPS) peak positions as a function of
      temperature and substrate polarization revealed no evidence of shifts from the
      peak positions expected for Cr2O3. The lack of any band offset between Cr2O3 on
      the oppositely poled surface suggests that charge compensation of the
      ferroelectric substrate occurs at least predominantly at the surface of the film,
      as opposed to the film-substrate interface. No evidence of shifts due to
      oxidation or reduction of the Cr was observed indicating that charge compensation
      did not involve a change in the ionic state of the Cr. Exposing the films to
      reactive oxygen species emitted from an oxygen plasma, however, caused a distinct
      high binding energy shoulder on the Cr 2p3/2 XPS peaks that could be associated
      with oxygen adsorption on surface Cr and concomitant oxidation to Cr(5+). This
      feature was used to gauge the concentration of O adatoms on the surfaces as a
      function of temperature for oppositely poled substrates; these measurements did
      not reveal any significant polarization dependence for oxygen desorption.
      Further, temperature programmed desorption measurements for a Cr2O3 film on alpha
      Al2O3 showed a similar trend in O2 desorption. Therefore, it is concluded that
      the reactivity of Cr2O3 toward O is at least largely independent of substrate
      polarization despite data suggestive of charge compensation at the film surfaces.

PMID- 25767834
TI  - Dissociative dynamics of O2 on Ag(110).
AB  - We study the dissociative dynamics of O2 on Ag(110) by performing classical and
      quasiclassical trajectory calculations on an adiabatic six-dimensional potential
      energy surface (PES). The PES is constructed from the interpolation of a large
      set of energies that are calculated using spin-polarized density functional
      theory. The minimum energy barrier to dissociation amounts to 0.36 eV. This
      value, which is considerably lower than the barriers of about 1.1 eV found in the
      Ag(100) and Ag(111) surfaces, is in line with the measured much higher reactivity
      of the (110) surface. Our classical dynamics calculations show that under normal
      incidence conditions no significant dissociation occurs below an initial energy
      of 0.9 eV (0.6 eV in the quasiclassical calculations). This result is an
      indication of a very much reduced configurational space leading to dissociation
      and also explains why direct dissociation has not been observed experimentally at
      low incidence energies. Our calculations also show that for off-normal incidence,
      most of the dissociation takes place close to the long-bridge site, a region of
      the configurational space where the energy barriers to dissociation are higher
      than 0.7 eV, resulting in still lower dissociation probabilities. 

PMID- 25767835
TI  - Structural, elastic and vibrational properties of nanocrystalline lutetium
      gallium garnet under high pressure.
AB  - An ab initio study of the structural, elastic and vibrational properties of the
      lutetium gallium garnet (Lu3Ga5O12) under pressure has been performed in the
      framework of the density functional theory, up to 95 GPa. Pressure dependence of
      the elastic constants and the mechanical stability are analyzed, showing that the
      garnet structure is mechanically unstable above 87 GPa. Lattice-dynamics
      calculations in bulk at different pressures have been performed and compared with
      Raman scattering measurements of the nanocrystalline Tm(3+)-doped Lu3Ga5O12 up to
      60 GPa. The theoretical frequencies and pressure coefficients of the Raman active
      modes for bulk Lu3Ga5O12 are in good agreement with the experimental data
      measured for the nano-crystals. The contributions of the different atoms to the
      vibrational modes have been analyzed based on the calculated total and partial
      phonon density of states. The vibrational modes have been discussed in relation
      to the internal and external modes of the GaO4 tetrahedron and the GaO6
      octahedron. The calculated infrared modes and their pressure dependence are also
      reported. Our results show that with this nano-garnet size the sample has
      essentially bulk properties. 

PMID- 25767836
TI  - Conformational steering in dicarboxy acids: the native structure of succinic
      acid.
AB  - Succinic acid, a dicarboxylic acid molecule, has been investigated
      spectroscopically with computational support to elucidate the complex aspects of
      its conformational composition. Due to the torsional freedom of the carbon
      backbone and hydroxy groups, a large number of potentially plausible conformers
      can be generated with an indication that the gauche conformer is favored over the
      trans form. The microwave and millimeter wave spectra have been analyzed and
      accurate spectroscopic constants have been derived that correlate best with those
      of the lowest energy gauche conformer. For an unambiguous conformational
      identification measurements were extended to the monosubstituted isotopologues,
      precisely determining the structural properties. Besides bond distances and
      angles, particularly the dihedral angle has been determined to be 67.76(11)
      degrees , confirming the anomalous tendency of the methylene units to favor
      gauche conformers when a short aliphatic segment is placed between two carbonyl
      groups. 

PMID- 25767837
TI  - Words of wisdom. Re: functional magnetic resonance imaging during urodynamic
      testing identifies brain structures initiating micturition.

PMID- 25767838
TI  - Cerebral blood flow regulation   during hypoxia.

PMID- 25767839
TI  - The carotid body and its relevance in pathophysiology.

PMID- 25767840
TI  - Response.

PMID- 25767842
TI  - American Academy of Nursing announced engagement in National Choosing Wisely
      Campaign.

PMID- 25767841
TI  - Same-sex partnership rights: health care decision making and hospital visitation.

PMID- 25767843
TI  - Response.

PMID- 25767844
TI  - Response.

PMID- 25767845
TI  - Social behaviour: Indecent advances.

PMID- 25767846
TI  - Measuring the psychosocial burden in women  with low-grade abnormal cervical
      cytology in the  TOMBOLA trial: psychometric properties of the  Process and
      Outcome Specific Measure (POSM).
AB  - Background: There is a need for an instrument to measure the psychosocial burden
      of receiving an abnormal cervical cytology result which can be used regardless of
      the clinical management women receive.Methods: 3331 women completed the POSM as
      part of baseline psychosocial assessment in a trial of management of low grade
      cervical cytological abnormalities. Factor analysis and reliability assessment of
      the POSM were conducted.Results: Two factors were extracted from the POSM: Factor
      1, containing items related to worry; and Factor 2 containing items relating to
      satisfaction with information and support received and change in the way women
      felt about themselves. Factor 1 had good reliability (Cronbach's alpha 0.769),
      however reliability of the Factor 2 was poorer(0.482). Data collected at four
      subsequent time points demonstrated that the factor structure was stable over
      time.Conclusion: This study demonstrates the presence and reliability of a scale
      measuring worries within the POSM. This analysis will inform its future use in
      this population and in other related contexts.

PMID- 25767847
TI  - Response.

PMID- 25767848
TI  - Captopril and lisinopril only inhibit matrix metalloproteinase-2 (MMP-2) activity
      at millimolar concentrations.
AB  - Matrix metalloproteinase-2 (MMP-2) shares structural similarities with the
      angiotensin-converting enzyme (ACE). ACE inhibitors have been described to
      inhibit MMP-2, but this inhibitory potential was not shown using a highly
      purified MMP-2. This study aimed to investigate the inhibitory potential of
      captopril and lisinopril regarding MMP-2 activity. The first objective was to
      test the potential of captopril to change the pH of the buffer solution. The
      second objective was to test the direct inhibitory effect of captopril and
      lisinopril on plasma MMP-2 and on recombinant human MMP-2 (rhMMP-2). The in vitro
      activity assays included gelatin zymography and a fluorimetric assay. Captopril
      solubilization significantly decreased the pH of the 50 mM Tris buffer solution
      at the following concentrations: 2 mM (p < 0.05), 4 mM and 8 mM (p < 0.01), while
      only the 8 mM lisinopril induced a drop in pH (p < 0.05). Thus, only 200 mM
      buffer solutions were used. Zymography results of plasma MMP-2 and rhMMP-2 showed
      that inhibition only happened at captopril concentrations >= 4 and 1 mM,
      respectively (p < 0.05), while only the higher concentration of lisinopril (8 mM)
      inhibited plasma MMP-2 (p < 0.05). In the fluorimetric assay, captopril led to
      significant inhibition of the rhMMP-2 activity at concentrations >=2 mM (p <
      0.01), whereas aminophenylmercuric acetate-activated rhMMP-2 was inhibited by 0.5
      mM captopril (p < 0.01). The captopril and lisinopril concentrations found to
      inhibit MMP-2 are 3 orders of magnitude higher than those present in vivo after
      drug administration. We also discuss possible pitfalls for gelatinase inhibitory
      assays (besides the obvious pH problem already cited). In conclusion, this
      study's data show that captopril and lisinopril did not inhibit MMP-2 directly at
      the concentrations reached in vivo.

PMID- 25767849
TI  - Editor's note for 'Post procedural pain withphotodynamic therapy is more severe
      than skinsurgery--prospective data'.

PMID- 25767850
TI  - Local-scale biogeography and spatiotemporal variability in  communities of
      mycorrhizal fungi.
AB  - Knowledge of spatiotemporal patterns in species distribution is fundamental to
      understanding the ecological and evolutionary processes shaping communities. The
      emergence of DNA-based tools has expanded the geographic and taxonomic scope of
      studies examining spatial and temporal distribution of mycorrhizal fungi.
      However, the nature of spatiotemporal patterns documented and subsequent
      interpretation of ecological processes can vary significantly from study to
      study. In order to look for general patterns we synthesize the available data
      across different sampling scales and mycorrhizal types. The results of this
      analysis shed light on the relative importance of space, time and vertical soil
      structure on community variability across different mycorrhizal types. Although
      we found no significant trend in spatiotemporal variation amongmycorrhizal types,
      the vertical community variation was distinctly greater than the spatial and
      temporal variability in mycorrhizal fungal communities. Both spatial and temporal
      variability of communities was greater in topsoil compared with lower horizons,
      suggesting that greater environmental heterogeneity drives community variation on
      a fine scale. This further emphasizes the importance of both niche
      differentiation and environmental filtering in maintaining diverse fungal
      communities.

PMID- 25767851
TI  - Author response.

PMID- 25767853
TI  - Retraction: Rgulation of Wnt/beta-catenin pathway by cPLA2 and PPARdelta.

PMID- 25767854
TI  - [The masochism puzzle. "Pain and pleasure have a common final pathway"].

PMID- 25767855
TI  - [Help for children with psychiatric illnesses. "We must consider the family"].

PMID- 25767856
TI  - [Is phimosis the cause? This boy is tormented by an itchy penis].

PMID- 25767857
TI  - [Progress in the treatment of ulcerative colitis].

PMID- 25767858
TI  - Berwick sees the possible in healthcare.

PMID- 25767859
TI  - Patients share more with computers than clinicians.

PMID- 25767860
TI  - Yes, you can ask about gun ownership.

PMID- 25767861
TI  - [Uncertain resuscitation standards for emergency physicians. The blind spots in
      emergency medicine].

PMID- 25767862
TI  - [On call service. May I not claim C-reactive protein test fee?].

PMID- 25767863
TI  - [Saturday office hours. One can also restrict consultation to prevention].

PMID- 25767864
TI  - [Risk factor for mental decline. First depressed, then demented?].

PMID- 25767865
TI  - [Effectiveness of antidepressants. Faith strengthens the cortex].

PMID- 25767866
TI  - [Are antidepressants a risk for the fetus?].

PMID- 25767867
TI  - [Acute bronchitis. Phytotherapy instead of antibiotic: proactive communication!].

PMID- 25767868
TI  - [Interview with PD Dr. Anton Gillessen, Munster. Non-alcoholic fatty liver:
      change in the life style!].

PMID- 25767869
TI  - [Vertigo in the elderly. Effective therapy options].

PMID- 25767870
TI  - Prostate field cancerization: deregulated expression of macrophage inhibitory
      cytokine 1 (MIC-1) and platelet derived growth factor A (PDGF-A) in tumor
      adjacent tissue.
AB  - Prostate field cancerization denotes molecular alterations in histologically
      normal tissues adjacent to tumors. Such alterations include deregulated protein
      expression, as we have previously shown for the key transcription factor early
      growth response 1 (EGR-1) and the lipogenic enzyme fatty acid synthase (FAS).
      Here we add the two secreted factors macrophage inhibitory cytokine 1 (MIC-1) and
      platelet derived growth factor A (PDGF-A) to the growing list of protein markers
      of prostate field cancerization. Expression of MIC-1 and PDGF-A was measured
      quantitatively by immunofluorescence and comprehensively analyzed using two
      methods of signal capture and several groupings of data generated in human
      cancerous (n = 25), histologically normal adjacent (n = 22), and disease-free (n
      = 6) prostate tissues. A total of 208 digitized images were analyzed. MIC-1 and
      PDGF-A expression in tumor tissues were elevated 7.1x to 23.4x and 1.7x to 3.7x
      compared to disease-free tissues, respectively (p<0.0001 to p = 0.08 and p<0.01
      to p = 0.23, respectively). In support of field cancerization, MIC-1 and PDGF-A
      expression in adjacent tissues were elevated 7.4x to 38.4x and 1.4x to 2.7x,
      respectively (p<0.0001 to p<0.05 and p<0.05 to p = 0.51, respectively). Also, MIC
      1 and PDGF-A expression were similar in tumor and adjacent tissues (0.3x to 1.0x;
      p<0.001 to p = 0.98 for MIC-1; 0.9x to 2.6x; p<0.01 to p = 1.00 for PDGF-A). All
      analyses indicated a high level of inter- and intra-tissue heterogeneity across
      all types of tissues (mean coefficient of variation of 86.0%). Our data shows
      that MIC-1 and PDGF-A expression is elevated in both prostate tumors and
      structurally intact adjacent tissues when compared to disease-free specimens,
      defining field cancerization. These secreted factors could promote tumorigenesis
      in histologically normal tissues and lead to tumor multifocality. Among several
      clinical applications, they could also be exploited as indicators of disease in
      false negative biopsies, identify areas of repeat biopsy, and add molecular
      information to surgical margins. 

PMID- 25767871
TI  - Tracking the fate of stem cell implants with fluorine-19 MRI.
AB  - BACKGROUND: In this study we used cellular magnetic resonance imaging (MRI) to
      detect mesenchymal stem cells (MSC) labeled with a Fluorine-19 (19F) agent. 19F
      MRI offers unambiguous detection and in vivo quantification of labeled cells.
      METHODS: We investigated two common stem cell transplant mouse models: an immune
      competent, syngeneic transplant model and an immune compromised, xenograft
      transplant model. 19F labelled stem cells were implanted intramuscularly into the
      hindlimb of healthy mice. The transplant was then monitored for up to 17 days
      using 19F-MRI, after which the tissue was excised for fluorescence microscopy and
      immunohistochemisty. RESULTS: Immediately following transplantation, 19F-MRI
      quantification correlated very well with the expected cell number in both models.
      The 19F signal decreased over time in both models, with a more rapid decrease in
      the syngeneic model. By endpoint, only 2/7 syngeneic mice had any detectable 19F
      signal. In the xenograft model, all mice had detectable signal at endpoint.
      Fluorescence microscopy and immunohistochemistry were used to show that the 19F
      signal was related to the presence of bystander labeled macrophages, and not
      original MSC. CONCLUSIONS: Our results show that 19F-MRI is an excellent tool for
      verifying the delivery of therapeutic cells early after transplantation. However,
      in certain circumstances the transfer of cellular label to other bystander cells
      may confuse interpretation of the long-term fate of the transplanted cells.

PMID- 25767872
TI  - Worldwide enucleation techniques and materials for treatment of retinoblastoma:
      an international survey.
AB  - PURPOSE: To investigate the current practice of enucleation with or without
      orbital implant for retinoblastoma in countries across the world. METHODS: A
      digital survey identifying operation techniques and material used for orbital
      implants after enucleation in patients with retinoblastoma. RESULTS: We received
      a response of 58 surgeons in 32 different countries. A primary artificial implant
      is routinely inserted by 42 (72.4%) surgeons. Ten (17.2%) surgeons leave the
      socket empty, three (5.2%) decide per case. Other surgeons insert a dermis fat
      graft as a standard primary implant (n=1), or fill the socket in a standard
      secondary procedure (n=2; one uses dermis fat grafts and one artificial
      implants). The choice for porous implants was more frequent than for non-porous
      implants: 27 (58.7%) and 15 (32.6%), respectively. Both porous and non-porous
      implant types are used by 4 (8.7%) surgeons. Twenty-five surgeons (54.3%) insert
      bare implants, 11 (23.9%) use separate wrappings, eight (17.4%) use implants with
      prefab wrapping and two insert implants with and without wrapping depending on
      type of implant. Attachment of the muscles to the wrapping or implant (at various
      locations) is done by 31 (53.4%) surgeons. Eleven (19.0%) use a myoconjunctival
      technique, nine (15.5%) suture the muscles to each other and seven (12.1%) do not
      reattach the muscles. Measures to improve volume are implant exchange at an older
      age (n=4), the use of Restylane SQ (n=1) and osmotic expanders (n=1). Pegging is
      done by two surgeons. CONCLUSION: No (worldwide) consensus exists about the use
      of material and techniques for enucleation for the treatment of retinoblastoma.
      Considerations for the use of different techniques are discussed.

PMID- 25767873
TI  - How moving backgrounds influence interception.
AB  - Reaching movements towards an object are continuously guided by visual
      information about the target and the arm. Such guidance increases precision and
      allows one to adjust the movement if the target unexpectedly moves. On-going arm
      movements are also influenced by motion in the surrounding. Fast responses to
      motion in the surrounding could help cope with moving obstacles and with the
      consequences of changes in one's eye orientation and vantage point. To further
      evaluate how motion in the surrounding influences interceptive movements we asked
      subjects to tap a moving target when it reached a second, static target. We
      varied the direction and location of motion in the surrounding, as well as
      details of the stimuli that are known to influence eye movements. Subjects were
      most sensitive to motion in the background when such motion was near the targets.
      Whether or not the eyes were moving, and the direction of the background motion
      in relation to the direction in which the eyes were moving, had very little
      influence on the response to the background motion. We conclude that the
      responses to background motion are driven by motion near the target rather than
      by a global analysis of the optic flow and its relation with other information
      about self-motion. 

PMID- 25767874
TI  - CCAAT/enhancer binding protein beta is dispensable for development of lung
      adenocarcinoma.
AB  - Lung cancer is the leading cause of cancer death worldwide. Although disruption
      of normal proliferation and differentiation is a vital component of
      tumorigenesis, the mechanisms of this process in lung cancer are still unclear. A
      transcription factor, C/EBPbeta is a critical regulator of proliferation and/or
      differentiation in multiple tissues. In lung, C/EBPbeta is expressed in alveolar
      pneumocytes and bronchial epithelial cells; however, its roles on normal lung
      homeostasis and lung cancer development have not been well described. Here we
      investigated whether C/EBPbeta is required for normal lung development and
      whether its aberrant expression and/or activity contribute to lung tumorigenesis.
      We showed that C/EBPbeta was expressed in both human normal pneumocytes and lung
      adenocarcinoma cell lines. We found that overall lung architecture was maintained
      in Cebpb knockout mice. Neither overexpression of nuclear C/EBPbeta nor
      suppression of CEBPB expression had significant effects on cell proliferation.
      C/EBPbeta expression and activity remained unchanged upon EGF stimulation.
      Furthermore, deletion of Cebpb had no impact on lung tumor burden in a lung
      specific, conditional mutant EGFR lung cancer mouse model. Analyses of data from
      The Cancer Genome Atlas (TCGA) revealed that expression, promoter methylation, or
      copy number of CEBPB was not significantly altered in human lung adenocarcinoma.
      Taken together, our data suggest that C/EBPbeta is dispensable for development of
      lung adenocarcinoma. 

PMID- 25767875
TI  - Fission yeast Scp3 potentially maintains microtubule orientation through
      bundling.
AB  - Microtubules play important roles in organelle transport, the maintenance of cell
      polarity and chromosome segregation and generally form bundles during these
      processes. The fission yeast gene scp3+ was identified as a multicopy suppressor
      of the cps3-81 mutant, which is hypersensitive to isopropyl N-3
      chlorophenylcarbamate (CIPC), a poison that induces abnormal multipolar spindle
      formation in higher eukaryotes. In this study, we investigated the function of
      Scp3 along with the effect of CIPC in the fission yeast Schizosaccharomyces
      pombe. Microscopic observation revealed that treatment with CIPC, cps3-81
      mutation and scp3+ gene deletion disturbed the orientation of microtubules in
      interphase cells. Overexpression of scp3+ suppressed the abnormal orientation of
      microtubules by promoting bundling. Functional analysis suggested that Scp3
      functions independently from Ase1, a protein largely required for the bundling of
      the mitotic spindle. A strain lacking the ase1+ gene was more sensitive to CIPC,
      with the drug affecting the integrity of the mitotic spindle, indicating that
      CIPC has a mitotic target that has a role redundant with Ase1. These results
      suggested that multiple systems are independently involved to ensure microtubule
      orientation by bundling in fission yeast. 

PMID- 25767876
TI  - Spot the difference-development of a syndrome based protein microarray for
      specific serological detection of multiple flavivirus infections in travelers.
AB  - BACKGROUND: The family Flaviviridae, genus Flavivirus, holds many of the world's
      most prevalent arboviral diseases that are also considered the most important
      travel related arboviral infections. In most cases, flavivirus diagnosis in
      travelers is primarily based on serology as viremia is often low and typically
      has already been reduced to undetectable levels when symptoms set in and patients
      seek medical attention. Serological differentiation between flaviviruses and the
      false-positive results caused by vaccination and cross-reactivity among the
      different species, are problematic for surveillance and diagnostics of
      flaviviruses. Their partially overlapping geographic distribution and symptoms,
      combined with increase in travel, and preexisting antibodies due to flavivirus
      vaccinations, expand the need for rapid and reliable multiplex diagnostic tests
      to supplement currently used methods. GOAL: We describe the development of a
      multiplex serological protein microarray using recombinant NS1 proteins for
      detection of medically important viruses within the genus Flavivirus. Sera from
      clinical flavivirus patients were used for primary development of the protein
      microarray. RESULTS: Results show a high IgG and IgM sensitivity and specificity
      for individual NS1 antigens, and limited cross reactivity, even within
      serocomplexes. In addition, the serology based on this array allows for
      discrimination between infection and vaccination response for JEV vaccine, and no
      cross-reactivity with TBEV and YFV vaccine induced antibodies when testing for
      antibodies to other flaviviruses. CONCLUSION: Based on these data, multiplex NS1
      based protein microarray is a promising tool for surveillance and diagnosis of
      flaviviruses.

PMID- 25767877
TI  - Retinal photoreceptor expresses toll-like receptors (TLRs) and elicits innate
      responses following TLR ligand and bacterial challenge.
AB  - Toll-like receptors (TLRs) play an important role in host defense against
      microbial pathogens. Our previous studies have shown that TLRs are expressed on
      various retinal cells (Microglia and Muller glia) and orchestrate retinal innate
      responses in bacterial endophthalmitis. In this study, we used a well
      characterized mouse cone photoreceptor cell line (661W); and demonstrated that
      these cells express all known TLRs. Although the stimulation of 661W cells with
      TLR ligands (Pam3Cys, PolyI:C, LPS, Flagellin, Poly DT, and ODN) did not alter
      TLR expression, downstream TLR-signaling pathways (NF-kappaB, p38, and ERK) are
      activated. Moreover, TLR-activated 661W cells secreted significant amounts of
      inflammatory mediators (IL-6, IL-1beta, MIP-2, and KC) in their culture
      supernatant, as assessed by ELISA. A similar trend was observed in 661W cells
      challenged with live bacteria (Staphylococcus aureus). Interestingly, the
      neutralization of TLR2, a major receptor for S. aureus recognition, did not
      significantly attenuate bacterial-induced inflammatory mediators, suggesting the
      existence of TLR2-independent mechanisms in photoreceptor cells. Together, these
      results indicate that photoreceptors constitutively express functional TLRs and
      possess the ability to initiate innate responses following pathogen challenge,
      implicating their role in retinal innate immunity. 

PMID- 25767878
TI  - The NDST gene family in zebrafish: role of NDST1B in pharyngeal arch formation.
AB  - Heparan sulfate (HS) proteoglycans are ubiquitous components of the extracellular
      matrix and plasma membrane of metazoans. The sulfation pattern of the HS
      glycosaminoglycan chain is characteristic for each tissue and changes during
      development. The glucosaminyl N-deacetylase/N-sulfotransferase (NDST) enzymes
      catalyze N-deacetylation and N-sulfation during HS biosynthesis and have a key
      role in designing the sulfation pattern. We here report on the presence of five
      NDST genes in zebrafish. Zebrafish ndst1a, ndst1b, ndst2a and ndst2b represent
      duplicated mammalian orthologues of NDST1 and NDST2 that arose through teleost
      specific genome duplication. Interestingly, the single zebrafish orthologue
      ndst3, is equally similar to tetrapod Ndst3 and Ndst4. It is likely that a local
      duplication in the common ancestor of lobe-finned fish and tetrapods gave rise to
      these two genes. All zebrafish Ndst genes showed distinct but partially
      overlapping expression patterns during embryonic development. Morpholino
      knockdown of ndst1b resulted in delayed development, craniofacial cartilage
      abnormalities, shortened body and pectoral fin length, resembling some of the
      features of the Ndst1 mouse knockout. 

PMID- 25767879
TI  - Hyperphosphorylation of intrinsically disordered tau protein induces an
      amyloidogenic shift in its conformational ensemble.
AB  - Tau is an intrinsically disordered protein (IDP) whose primary physiological role
      is to stabilize microtubules in neuronal axons at all stages of development. In
      Alzheimer's and other tauopathies, tau forms intracellular insoluble amyloid
      aggregates known as neurofibrillary tangles, a process that appears in many cases
      to be preceded by hyperphosphorylation of tau monomers. Understanding the shift
      in conformational bias induced by hyperphosphorylation is key to elucidating the
      structural factors that drive tau pathology, however, as an IDP, tau is not
      amenable to conventional structural characterization. In this work, we employ a
      straightforward technique based on Time-Resolved ElectroSpray Ionization Mass
      Spectrometry (TRESI-MS) and Hydrogen/Deuterium Exchange (HDX) to provide a
      detailed picture of residual structure in tau, and the shifts in conformational
      bias induced by hyperphosphorylation. By comparing the native and
      hyperphosphorylated ensembles, we are able to define specific conformational
      biases that can easily be rationalized as enhancing amyloidogenic propensity.
      Representative structures for the native and hyperphosphorylated tau ensembles
      were generated by refinement of a broad sample of conformations generated by low
      computational complexity modeling, based on agreement with the TRESI-HDX
      profiles. 

PMID- 25767880
TI  - Circulating level of CTRP1 in patients with nonalcoholic fatty liver disease
      (NAFLD): is it through insulin resistance?
AB  - Nonalcoholic fatty liver disease (NAFLD) is considered as one of the most common
      liver diseases. It is robustly linked to obesity and insulin resistance and is
      regarded as hepatic manifestation of metabolic syndrome (MetS). Adipokines are
      involved in the pathophysiology of liver diseases. The aim of this study was to
      evaluate the plasma concentrations of CTRP1 (complement-C1q TNF-related protein
      1) in 22 patients with NAFLD, 22 patients with type 2 diabetes mellitus (T2DM),
      22 patients with NAFLD+T2DM and 21 healthy controls, as well as their correlation
      with the level of metabolic and hepatic parameters. Plasma concentration of CTRP1
      was measured with ELISA method. Plasma concentration of CTRP1 in patients with
      NAFLD, T2DM and NAFLD+T2DM were significantly higher than healthy subjects
      (p<0.0001). Moreover, we observed significant positive correlations between
      plasma level of CTRP1 and fasting blood glucose (FBG) (p<0.001), homeostasis
      model assessment of insulin resistance (HOMA-IR) (p<0.001), body mass index (BMI)
      (p = 0.001), alanine amino transferase (ALT) (p = 0.002), gamma glutamyl
      transferase (gamma-GT) (p<0.001) and liver stiffness (LS) (p<0.001). Our results
      indicate the strong association of CTRP1 with insulin resistance in NAFLD. Also,
      it seems that CTRP1 can be considered as an emerging biomarker for NAFLD,
      however, more studies are necessary to unravel the role of CTRP1 in NAFLD
      pathogenesis. 

PMID- 25767881
TI  - Diminished response of arctic plants to warming over time.
AB  - The goal of this study is to determine if the response of arctic plants to
      warming is consistent across species, locations and time. This study examined the
      impact of experimental warming and natural temperature variation on plants at
      Barrow and Atqasuk, Alaska beginning in 1994. We considered observations of plant
      performance collected from 1994-2000 "short-term" and those from 2007-2012 "long
      term". The plant traits reported are the number of inflorescences, inflorescence
      height, leaf length, and day of flower emergence. These traits can inform us
      about larger scale processes such as plant reproductive effort, plant growth, and
      plant phenology, and therefore provide valuable insight into community dynamics,
      carbon uptake, and trophic interactions. We categorized traits of all species
      monitored at each site into temperature response types. We then compared response
      types across traits, plant growth forms, sites, and over time to analyze the
      consistency of plant response to warming. Graminoids were the most responsive to
      warming and showed a positive response to temperature, while shrubs were
      generally the least responsive. Almost half (49%) of response types (across all
      traits, species, and sites combined) changed from short-term to long-term. The
      percent of plants responsive to warming decreased from 57% (short-term) to 46%
      (long-term). These results indicate that the response of plants to warming varies
      over time and has diminished overall in recent years. 

PMID- 25767883
TI  - A streamlined artificial variable free version of simplex method.
AB  - This paper proposes a streamlined form of simplex method which provides some
      great benefits over traditional simplex method. For instance, it does not need
      any kind of artificial variables or artificial constraints; it could start with
      any feasible or infeasible basis of an LP. This method follows the same pivoting
      sequence as of simplex phase 1 without showing any explicit description of
      artificial variables which also makes it space efficient. Later in this paper, a
      dual version of the new method has also been presented which provides a way to
      easily implement the phase 1 of traditional dual simplex method. For a problem
      having an initial basis which is both primal and dual infeasible, our methods
      provide full freedom to the user, that whether to start with primal artificial
      free version or dual artificial free version without making any reformulation to
      the LP structure. Last but not the least, it provides a teaching aid for the
      teachers who want to teach feasibility achievement as a separate topic before
      teaching optimality achievement. 

PMID- 25767882
TI  - Enterovirus 71 infection causes severe pulmonary lesions in gerbils, meriones
      unguiculatus, which can be prevented by passive immunization with specific
      antisera.
AB  - Neurogenic pulmonary edema caused by severe brainstem encephalitis is the leading
      cause of death in young children infected by Enterovirus 71 (EV71). However, no
      pulmonary lesions have been found in EV71-infected transgenic or non-transgenic
      mouse models. Development of a suitable animal model is important for studying
      EV71 pathogenesis and assessing effect of therapeutic approaches. We had found
      neurological disorders in EV71-induced young gerbils previously. Here, we report
      severe pulmonary lesions characterized with pulmonary congestion and hemorrhage
      in a gerbil model for EV71 infection. In the EV71-infected gerbils, six 21-day
      old or younger gerbils presented with a sudden onset of symptoms and rapid
      illness progression after inoculation with 1*105.5 TCID50 of EV71 via
      intraperitoneal (IP) or intramuscular (IM) route. Respiratory symptoms were
      observed along with interstitial pneumonia, pulmonary congestion and extensive
      lung hemorrhage could be detected in the lung tissues by histopathological
      examination. EV71 viral titer was found to be peak at late stages of infection.
      EV71-induced pulmonary lesions, together with severe neurological disorders were
      also observed in gerbils, accurately mimicking the disease process in EV71
      infected patients. Passive transfer with immune sera from EV71 infected adult
      gerbils with a neutralizing antibody (GMT=89) prevented severe pulmonary lesion
      formation after lethal EV71 challenge. These results establish this gerbil model
      as a useful platform for studying the pathogenesis of EV71-induced pulmonary
      lesions, immunotherapy and antiviral drugs. 

PMID- 25767885
TI  - Hurricane risk variability along the Gulf of Mexico coastline.
AB  - Hurricane risk characteristics are examined across the U. S. Gulf of Mexico
      coastline using a hexagonal tessellation. Using an extreme value model,
      parameters are collected representing the rate or lambda (frequency), the scale
      or sigma (range), and the shape or xi (intensity) of the extreme wind
      distribution. These latent parameters and the 30-year return level are visualized
      across the grid. The greatest 30-year return levels are located toward the center
      of the Gulf of Mexico, and for inland locations, along the borders of Louisiana,
      Mississippi, and Alabama. Using a geographically weighted regression model, the
      relationship of these parameters to sea surface temperature (SST) is found to
      assess sensitivity to change. It is shown that as SSTs increase near the coast,
      the frequency of hurricanes in these grids decrease significantly. This
      reinforces the importance of SST in areas of likely tropical cyclogenesis in
      determining the number of hurricanes near the coast, along with SSTs along the
      lifespan of the storm, rather than simply local SST. The range of hurricane wind
      speeds experienced near Florida is shown to increase with increasing SSTs
      (insignificant), suggesting that increased temperatures may allow hurricanes to
      maintain their strength as they pass over the Florida peninsula. The modifiable
      areal unit problem is assessed using multiple grid sizes. Moran's I and the local
      statistic G are calculated to examine spatial autocorrelation in the parameters.
      This research opens up future questions regarding rapid intensification and decay
      close to the coast and the relationship to changing SSTs. 

PMID- 25767884
TI  - Specific deletion of AMP-activated protein kinase (alpha1AMPK) in murine oocytes
      alters junctional protein expression and mitochondrial physiology.
AB  - Oogenesis and folliculogenesis are dynamic processes that are regulated by
      endocrine, paracrine and autocrine signals. These signals are exchanged between
      the oocyte and the somatic cells of the follicle. Here we analyzed the role of
      AMP-activated protein kinase (AMPK), an important regulator of cellular energy
      homeostasis, by using transgenic mice deficient in alpha1AMPK specifically in the
      oocyte. We found a decrease of 27% in litter size was observed in ZP3-alpha1AMPK
      /- (ZP3-KO) female mice. Following in vitro fertilization, where conditions are
      stressful for the oocyte and embryo, ZP3-KO oocytes were 68% less likely to pass
      the 2-cell stage. In vivo and in cumulus-oocyte complexes, several proteins
      involved in junctional communication, such as connexin37 and N-cadherin were down
      regulated in the absence of alpha1AMPK. While the two signalling pathways (PKA
      and MAPK) involved in the junctional communication between the cumulus/granulosa
      cells and the oocyte were stimulated in control oocytes, ZP3-KO oocytes exhibited
      only low phosphorylation of MAPK or CREB proteins. In addition, MII oocytes
      deficient in alpha1AMPK had a 3-fold lower ATP concentration, an increase in
      abnormal mitochondria, and a decrease in cytochrome C and PGC1alpha levels,
      suggesting perturbed energy production by mitochondria. The absence of alpha1AMPK
      also induced a reduction in histone deacetylase activity, which was associated
      with an increase in histone H3 acetylation (K9/K14 residues). Together, the
      results of the present study suggest that absence of AMPK, modifies oocyte
      quality through energy processes and oocyte/somatic cell communication. The
      limited effect observed in vivo could be partly due to a favourable follicle
      microenvironment where nutrients, growth factors, and adequate cell interaction
      were present. Whereas in a challenging environment such as that of in vitro
      culture following IVF, the phenotype is revealed. 

PMID- 25767886
TI  - Impact of a dengue outbreak experience in the preventive perceptions of the
      community from a temperate region: Madeira Island, Portugal.
AB  - The ability to effectively modify behaviours is increasingly relevant to attain
      and maintain a good health status. Current behaviour-change models and theories
      present two main approaches for (healthier) decision-making: one
      analytical/logical, and one experiential/emotional/intuitive. Therefore, to
      achieve an integral and dynamic understanding of the public perceptions both
      approaches should be considered: community surveys should measure cognitive
      understanding of health-risk contexts, and also explore how past experiences
      affect this understanding. In 2011, community perceptions regarding domestic
      source reduction were assessed in Madeira Island?. After Madeira's first dengue
      outbreak (2012) a unique opportunity to compare perceptions before and after the
      outbreak-experience occurred. This was the aim of this study, which constituted
      the first report on the effect of an outbreak experience on community perceptions
      regarding a specific vector-borne disease. A cross-sectional survey was performed
      within female residents at the most aegypti-infested areas. Perceptions regarding
      domestic source reduction were assessed according to the Essential Perception
      (EP)-analysis tool. A matching process paired individuals from studies performed
      before and after the outbreak, ensuring homogeneity in six determinant variables.
      After the outbreak, there were more female residents who assimilated the concepts
      considered to be essential to understand the proposed behaviour. Nevertheless, no
      significant difference was observed in the number of female residents who
      achieved the defined 'minimal understanding''. Moreover, most of the population
      (95.5%) still believed at least in one of the identified myths. After the
      outbreak some myths disappeared and others appeared. The present study quantified
      and explored how the experience of an outbreak influenced the perception
      regarding a dengue-preventive behaviour. The outbreak experience surprisingly led
      to the appearance of new myths within the population, apart from the expected
      increase of relevant concepts' assimilation. Monitoring public perceptions is
      therefore crucial to make preventing dengue campaigns updated and worthy. 

PMID- 25767887
TI  - A neural mechanism for background information-gated learning based on axonal
      dendritic overlaps.
AB  - Experiencing certain events triggers the acquisition of new memories. Although
      necessary, however, actual experience is not sufficient for memory formation. One
      trial learning is also gated by knowledge of appropriate background information
      to make sense of the experienced occurrence. Strong neurobiological evidence
      suggests that long-term memory storage involves formation of new synapses. On the
      short time scale, this form of structural plasticity requires that the axon of
      the pre-synaptic neuron be physically proximal to the dendrite of the post
      synaptic neuron. We surmise that such "axonal-dendritic overlap" (ADO)
      constitutes the neural correlate of background information-gated (BIG) learning.
      The hypothesis is based on a fundamental neuroanatomical constraint: an axon must
      pass close to the dendrites that are near other neurons it contacts. The
      topographic organization of the mammalian cortex ensures that nearby neurons
      encode related information. Using neural network simulations, we demonstrate that
      ADO is a suitable mechanism for BIG learning. We model knowledge as associations
      between terms, concepts or indivisible units of thought via directed graphs. The
      simplest instantiation encodes each concept by single neurons. Results are then
      generalized to cell assemblies. The proposed mechanism results in learning real
      associations better than spurious co-occurrences, providing definitive cognitive
      advantages. 

PMID- 25767888
TI  - Structure-based virtual screening and discovery of New PPARdelta/gamma dual
      agonist and PPARdelta and gamma agonists.
AB  - Peroxisome proliferator-activated receptors (PPARs) are involved in the control
      of carbohydrate and lipid metabolism and are considered important targets to
      treat diabetes mellitus and metabolic syndrome. The available PPAR ligands have
      several side effects leading to health risks justifying the search for new
      bioactive ligands to activate the PPAR subtypes, in special PPARdelta, the less
      studied PPAR isoform. Here, we used a structure-based virtual screening protocol
      in order to find out new PPAR ligands. From a lead-like subset of purchasable
      compounds, we identified 5 compounds with potential PPAR affinity and, from
      preliminary in vitro assays, 4 of them showed promising biological activity.
      Therefore, from our in silico and in vitro protocols, new PPAR ligands are
      potential candidates to treat metabolic diseases. 

PMID- 25767889
TI  - TORC1 promotes phosphorylation of ribosomal protein S6 via the AGC kinase Ypk3 in
      Saccharomyces cerevisiae.
AB  - The target of rapamycin complex 1 (TORC1) is an evolutionarily conserved sensor
      of nutrient availability. Genetic and pharmacological studies in the yeast
      Saccharomyces cerevisiae have provided mechanistic insights on the regulation of
      TORC1 signaling in response to nutrients. Using a highly specific antibody that
      recognizes phosphorylation of the bona fide TORC1 target ribosomal protein S6
      (Rps6) in yeast, we found that nutrients rapidly induce Rps6 phosphorylation in a
      TORC1-dependent manner. Moreover, we demonstrate that Ypk3, an AGC kinase which
      exhibits high homology to human S6 kinase (S6K), is required for the
      phosphorylation of Rps6 in vivo. Rps6 phosphorylation is completely abolished in
      cells lacking Ypk3 (ypk3Delta), whereas Sch9, previously reported to be the yeast
      ortholog of S6K, is dispensable for Rps6 phosphorylation. Phosphorylation
      deficient mutations in regulatory motifs of Ypk3 abrogate Rps6 phosphorylation,
      and complementation of ypk3Delta cells with human S6 kinase restores Rps6
      phosphorylation in a rapamycin-sensitive manner. Our findings demonstrate that
      Ypk3 is a critical component of the TORC1 pathway and that the use of a phospho
      S6 specific antibody offers a valuable tool to identify new nutrient-dependent
      and rapamycin-sensitive targets in vivo. 

PMID- 25767890
TI  - miR-185 plays an anti-hypertrophic role in the heart via multiple targets in the
      calcium-signaling pathways.
AB  - MicroRNA (miRNA) is an endogenous non-coding RNA species that either inhibits RNA
      translation or promotes degradation of target mRNAs. miRNAs often regulate
      cellular signaling by targeting multiple genes within the pathways. In the
      present study, using Gene Set Analysis, a useful bioinformatics tool to identify
      miRNAs with multiple target genes in the same pathways, we identified miR-185 as
      a key candidate regulator of cardiac hypertrophy. Using a mouse model, we found
      that miR-185 was significantly down-regulated in myocardial cells during cardiac
      hypertrophy induced by transverse aortic constriction. To confirm that miR-185 is
      an anti-hypertrophic miRNA, genetic manipulation studies such as overexpression
      and knock-down of miR-185 in neonatal rat ventricular myocytes were conducted.
      The results showed that up-regulation of miR-185 led to anti-hypertrophic
      effects, while down-regulation led to pro-hypertrophic effects, suggesting that
      miR-185 has an anti-hypertrophic role in the heart. Our study further identified
      Camk2d, Ncx1, and Nfatc3 as direct targets of miR-185. The activity of Nuclear
      Factor of Activated T-cell (NFAT) and calcium/calmodulin-dependent protein kinase
      II delta (CaMKIIdelta) was negatively regulated by miR-185 as assessed by NFAT
      luciferase activity and western blotting. The expression of phospho-phospholamban
      (Thr-17), a marker of CaMKIIdelta activity, was also significantly reduced by miR
      185. In conclusion, miR-185 effectively blocked cardiac hypertrophy signaling
      through multiple targets, rendering it a potential drug target for diseases such
      as heart failure. 

PMID- 25767891
TI  - Significant reduction of antibiotic consumption and patients' costs after an
      action plan in China, 2010-2014.
AB  - INTRODUCTION: On July 1, 2011, the Chinese government launched a national Action
      Plan for antibiotic stewardship targeting antibiotic misuse in public hospitals.
      The aim of this study was to evaluate the impacts of the Action Plan in terms of
      frequency and intensity of antibiotic utilization and patients costs in public
      general hospitals. METHODS: Administrative pharmacy data from July 2010 to June
      2014 were sampled from 65 public general hospitals and divided into three
      segments: (1) July 2010 to June 2011 as the preparation period; (2) July 2011 to
      June 2012 as the intervention period; and (3) July 2012 to June 2014 as the
      assessment period. The outcome measures included (1) antibiotic prescribing
      rates; (2) intensity of antibiotic consumption; (3) patients costs; and (4)
      duration of peri-operative antibiotic treatment in clean surgeries of
      thyroidectomy, breast, hernia, and orthopedic procedures. Longitudinal and cross
      sectional analyses were conducted. RESULTS: Longitudinal analyses showed
      significant trend changes in the frequency and intensity of antibiotic
      consumption, the patients' costs on antibiotics, and the duration of antibiotic
      treatment received by surgical patients undergoing the 4 clean procedures during
      the intervention period. Cross-sectional analyses showed that the antibiotic
      prescribing rates were reduced to 35.3% and 12.9% in inpatient and outpatient
      settings, that the intensity of antibiotic consumption was reduced to 35.9
      DDD/100 bed-days, that patients' costs on antibiotics were reduced significantly,
      and that the duration of peri-operative antibiotic treatment received by surgical
      patients undergoing the 4 types of clean procedures decreased to less than 24
      hour during the assessment period. CONCLUSION: The Action Plan, as a combination
      of managerial and professional strategies, was effective in reducing the
      frequency and intensity of antibiotic consumption, patients' costs on
      antibiotics, and the duration of peri-operative antibiotic treatment in the 4
      clean surgeries.

PMID- 25767893
TI  - Phenotypic and genotypic characterization of four factor VII deficiency patients
      from central China.
AB  - Hereditary coagulation factor VII deficiency (FVIID) is a rare autosomal,
      recessive inherited hemorrhagic disorder related to a variety of mutations or
      polymorphisms throughout the factor VII (FVII) gene (F7). The aims of this study
      were to characterize the molecular defect of the F7 gene in four unrelated
      patients with FVIID and to find the genotype-phenotype correlation. All nine
      exons, exon-intron boundaries, and 5' and 3'-untranslated regions of the F7 gene
      were amplified by PCR and the purified PCR products were sequenced directly.
      Suspected mutations were confirmed by another PCR and sequencing of the opposite
      strand. Family studies were also performed. A total of five unique lesions were
      identified, including three missense mutations (c.384A>G, c.839A>C, c.1163T>G,
      predicting p.Tyr128Cys, p.Glu280Ala and p.Phe388Cys substitution, respectively)
      and two splice junction mutations (c.572-1G>A, c.681+1G>T), among which two
      (p.Glu280Ala, p.Phe388Cys) were novel. A previously reported mutation p.Tyr128Cys
      was seen in the homozygous state in two unrelated patients. The other two cases
      were both compound heterozygotes of a missense mutation and a splicing site
      mutation. Multiple sequence alignment using DNAMAN analysis showed that all the
      missense mutations were found in residues that highly conserved across species
      and vitamin K-dependent serine proteases. Online software Polyphen and SIFT were
      used to confirm the pathogenic of the missense mutation. p.Tyr128Cys seems to be
      a hotspot of the F7 gene in ethnic Han Chinese population. 

PMID- 25767892
TI  - Paternal Urinary Concentrations of Parabens and Other Phenols in Relation to
      Reproductive Outcomes among Couples from a Fertility Clinic.
AB  - BACKGROUND: Human exposure to phenols, including bisphenol A and parabens, is
      widespread. Evidence suggests that paternal exposure to environmental chemicals
      may adversely affect reproductive outcomes. OBJECTIVES: We evaluated associations
      of paternal phenol urinary concentrations with fertilization rate, embryo
      quality, implantation, and live birth. METHODS: Male-female couples who underwent
      in vitro fertilization (IVF) and/or intrauterine insemination (IUI) cycles in a
      prospective study of environmental determinants of fertility and pregnancy
      outcomes were included. The geometric mean of males' specific gravity-adjusted
      urinary phenol concentrations measured before females' cycle was quantified.
      Associations between male urinary phenol concentrations and fertilization rate,
      embryo quality, implantation, and live birth were investigated using generalized
      linear mixed models to account for multiple cycles per couple. RESULTS: Couples
      (n = 218) underwent 195 IUI and 211 IVF cycles. Paternal phenol concentrations
      were not associated with fertilization or live birth following IVF. In adjusted
      models, compared with the lowest quartile of methyl paraben, paternal
      concentrations in the second quartile were associated with decreased odds of live
      birth following IUI (adjusted odds ratio = 0.19; 95% CI: 0.04, 0.82).
      CONCLUSIONS: To our knowledge, these are some of the first data on the
      association of paternal urinary phenol concentrations with reproduction and
      pregnancy outcomes. Although these results do not preclude possible adverse
      effects of paternal paraben exposures on such outcomes, given the modest sample
      size, further understanding could result from confirmation using a larger and
      more diverse population.

PMID- 25767894
TI  - Utility of a high VWF: FVIII ratio in preventing FVIII accumulation: a study in
      VWF-deficient mice.
AB  - Treatment of von Willebrand disease typically requires multiple infusions of von
      Willebrand factor (VWF)/factor VIII (FVIII) concentrate. Accumulation of FVIII is
      a clinical concern due to potential risk for thromboembolism. This study sought
      to determine whether VWF/FVIII concentrate of high VWF:FVIII ratio can prevent
      FVIII accumulation. VWF-deficient knockout mice received four 150 IU/kg
      VWF:ristocetin cofactor (RCo) infusions at 3-h intervals, with VWF/FVIII
      concentrates of a high (Haemate P/Humate-P) or low (Wilate) VWF:FVIII ratio.
      After each infusion, trough FVIII and VWF levels in plasma were determined.
      Separately, pharmacokinetic analysis was performed after single 250-IU/kg VWF:RCo
      infusions of each concentrate. Over the course of the four infusions, trough
      FVIII increased significantly in the group receiving Wilate (P < 0.001), but not
      Haemate P/Humate P (P = 0.058). After the first infusion, mean trough FVIII level
      in the Wilate group (31.7 IU/dl) was greater by 82% (P = 0.017) than that in the
      Haemate P/Humate P group (17.4 IU/dl). After the final infusion, mean trough
      FVIII of animals receiving Wilate (55.1 IU/dl) continued to exceed that of
      Haemate P/Humate P recipients (30.2 IU/dl) significantly (P < 0.001). Trough VWF
      levels were similar in the two groups. The VWF pharmacokinetics of the two
      concentrates coincided closely; however, the FVIII peak concentration and area
      under the curve were approximately twice as great in the mice treated with
      Wilate. In a murine model of severe von Willebrand disease, a VWF/FVIII
      concentrate with a high VWF:FVIII ratio prevented persistent exposure to elevated
      trough FVIII levels. 

PMID- 25767895
TI  - Adult severe haemophilia A patients under long-term prophylaxis with factor VIII
      in routine clinical practice.
AB  - There is no clear consensus on the best practice for long-term prophylaxis in
      adults with severe haemophilia A. This is a single-centre prospective case series
      study. We describe here the demographic data, type and reason of prophylaxis in
      adult patients (>18 years old) with severe (<1%) haemophilia A, treated in our
      centre from 2006 to 2013. Prophylaxis was tailored according to pharmacokinetic
      studies and posterior factor VIII (FVIII) trough level adjustment. We analysed
      FVIII consumption, bleeding rate, adherence and adverse events in this group of
      patients. In adult patients who initiated long-term prophylaxis during this
      period, we compared FVIII consumption and bleeding rate with the previous on
      demand period. We analysed data from 18 patients. Median annual FVIII consumption
      was 2374.2 IU/kg/year. Among the patients receiving tertiary prophylaxis,
      initiated from 2006 onwards, the annual FVIII consumption was 2557.8 vs. 1696.8
      IU/kg per year during the on-demand period (P = 0.312). In this group of
      patients, there was a decrease in annual bleeding events of 88.3% during
      prophylaxis compared with the on-demand therapy (P < 0.0001). A high adherence to
      prophylaxis was observed (84%). No cases of anaphylaxis or symptomatic
      thromboembolic events were recorded. In adult severe haemophilia A patients, the
      type of and reason to indicate long-term prophylaxis are diverse nowadays. FVIII
      consumption varies depending on the justification of prophylaxis. The
      observations reported provide further support for the efficacy of long-term
      prophylaxis in adult haemophilia A patients. 

PMID- 25767896
TI  - The effect of Helicobacter pylori eradication therapy on the development of
      gastroesophageal reflux disease.
AB  - BACKGROUND: It is uncertain whether the Helicobacter pylori eradication therapy
      makes a role in the progression of gastroesophageal reflux disease (GERD).
      METHODS: A meta-analysis was undertaken to investigate the effect of H pylori
      eradication therapy on the development of GERD. RESULTS: Overall, 16 cohort
      studies were included. The authors demonstrated that H pylori eradication had no
      significant effect on the occurrence of GERD in these cohort studies (odds ratio
      = 0.87, 95% confidence interval = 0.66-1.14, I = 32.4%, P = 0.103). CONCLUSIONS:
      In general, H pylori eradication has no significant effect on the development of
      GERD in the long term. However, eradication therapy should be taken once there is
      H pylori infection, because H pylori infection is acknowledged to be a major
      cause of acute and chronic gastritis and peptic ulcer diseases and has been
      established as a definite etiologic factor for gastric cancer.

PMID- 25767897
TI  - Electrospray-processed soluble acenes toward the realization of high-performance
      field-effect transistors.
AB  - Functionalized acenes have proven to be promising compounds in the field of
      molecular electronics because of their unique features in terms of the stability,
      performance, and ease of processing. The emerging concept of large-area
      compatible techniques for flexible electronics has brought about a wide variety
      of well-established techniques for the deposition of soluble acenes, with spray
      coating representing an especially fruitful approach. In the present study,
      electrostatic spray deposition is proposed as an alternative to the conventional
      spray-coating processes, toward the realization of high-performance organic field
      effect transistors (OFETs), on both rigid and flexible substrates. Particularly,
      a thorough study on the effect of the solvent and spraying regime on the
      resulting crystalline film's morphology is performed. By optimization of the
      process conditions in terms of control over the size as well as the
      crystallization scheme of the droplets, desirable morphological features along
      with high-quality crystal domains are obtained. The fabricated OFETs exhibit
      excellent electrical characteristics, with high field-effect mobility up to 0.78
      cm(2)/(V s), I(on)/I(off) >10(4), and near-zero threshold voltages. Additionally,
      the good performance of the OFETs realized on plastic substrates gives great
      potentiality to the proposed method for applications in the challenging field of
      large-area electronics.

PMID- 25767898
TI  - Accelerated gradient-based free form deformable registration for online adaptive
      radiotherapy.
AB  - The registration of planning fan-beam computed tomography (FBCT) and daily cone
      beam CT (CBCT) is a crucial step in adaptive radiation therapy. The current
      intensity-based registration algorithms, such as Demons, may fail when they are
      used to register FBCT and CBCT, because the CT numbers in CBCT cannot exactly
      correspond to the electron densities. In this paper, we investigated the effects
      of CBCT intensity inaccuracy on the registration accuracy and developed an
      accurate gradient-based free form deformation algorithm (GFFD). GFFD
      distinguishes itself from other free form deformable registration algorithms by
      (a) measuring the similarity using the 3D gradient vector fields to avoid the
      effect of inconsistent intensities between the two modalities; (b) accommodating
      image sampling anisotropy using the local polynomial approximation-intersection
      of confidence intervals (LPA-ICI) algorithm to ensure a smooth and continuous
      displacement field; and (c) introducing a 'bi-directional' force along with an
      adaptive force strength adjustment to accelerate the convergence process. It is
      expected that such a strategy can decrease the effect of the inconsistent
      intensities between the two modalities, thus improving the registration accuracy
      and robustness. Moreover, for clinical application, the algorithm was implemented
      by graphics processing units (GPU) through OpenCL framework. The registration
      time of the GFFD algorithm for each set of CT data ranges from 8 to 13 s. The
      applications of on-line adaptive image-guided radiation therapy, including auto
      propagation of contours, aperture-optimization and dose volume histogram (DVH) in
      the course of radiation therapy were also studied by in-house-developed software.

PMID- 25767899
TI  - Unusual retinopathy associated with hemochromatosis.
AB  - PURPOSE: To describe unusual retinal findings of a patient affected by
      hemochromatosis. METHODS: Case report of a 49-year-old patient who presented a
      progressive loss of vision. Fundus photography, fluorescein angiography, full
      field electroretinogram, autofluorescence imaging, and spectral domain optical
      coherence tomography were performed. The patient was known to be homozygous for
      the C282Y mutation in the HFE gene. RESULTS: Visual acuity was measured at 20/20
      on his right eye and 20/25 on his left eye. Retinal imaging showed alterations of
      the retinal pigment epithelium clearly visible on fundus autofluorescence and
      fluorescein angiography. The spectral domain optical coherence tomography showed
      retinal pigmentary epithelial atrophy associated with irregularities and focal
      interruption of the ellipsoid zone. A thin retina was also observed in the
      foveolar region associated to a thickened choroid. Full-field electroretinogram
      showed a decrease of rods and cones responses. CONCLUSION: Here, the authors
      describe the retinal findings of a patient affected by hemochromatosis,
      characterized by unusual retinal pigment epithelium changes associated to altered
      visual function. The authors hypothesize that the retinopathy could be linked to
      hemochromatosis because of the pathophysiology of iron homeostasis and the
      toxicity of iron overload for the photoreceptors.

PMID- 25767900
TI  - Chandelier-assisted external drainage of subretinal fluid.
AB  - PURPOSE: External drainage could be indicated for long-standing nonresolving
      exudative retinal detachment secondary to chronic central serous
      chorioretinopathy, capillary hemangioma, and Coats disease. The authors report a
      modified technique of external drainage of subretinal fluid using Chandelier
      illumination. METHODS: Muscles were tagged after conjunctival exposure. After
      placing the Chandelier illumination at the 12-o'clock position, 26-gauge needle
      attached with cannula is inserted externally at the equator into the subretinal
      space. Under direct visualization through surgical microscope, subretinal fluid
      was slowly removed and the needle was withdrawn. After maintaining the
      intraocular pressure, retina was examined and was found to be attached. RESULTS:
      Successful removal of subretinal fluid achieved without any complications.
      CONCLUSION: Chandelier-assisted external drainage of subretinal fluid is easier,
      well-controlled, and a convenient technique, which provides continuous direct
      visualization during external drainage of subretinal fluid to achieve excellent
      anatomical and visual outcome and prevent complications.

PMID- 25767901
TI  - The Effects of Social Anxiety and State Anxiety on Visual Attention: Testing the
      Vigilance-Avoidance Hypothesis.
AB  - A growing theoretical and research literature suggests that trait and state
      social anxiety can predict attentional patterns in the presence of emotional
      stimuli. The current study adds to this literature by examining the effects of
      state anxiety on visual attention and testing the vigilance-avoidance hypothesis,
      using a method of continuous visual attentional assessment. Participants were 91
      undergraduate college students with high or low trait fear of negative evaluation
      (FNE), a core aspect of social anxiety, who were randomly assigned to either a
      high or low state anxiety condition. Participants engaged in a free view task in
      which pairs of emotional facial stimuli were presented and eye movements were
      continuously monitored. Overall, participants with high FNE avoided angry stimuli
      and participants with high state anxiety attended to positive stimuli.
      Participants with high state anxiety and high FNE were avoidant of angry faces,
      whereas participants with low state and low FNE exhibited a bias toward angry
      faces. The study provided partial support for the vigilance-avoidance hypothesis.
      The findings add to the mixed results in the literature that suggest that both
      positive and negative emotional stimuli may be important in understanding the
      complex attention patterns associated with social anxiety. Clinical implications
      and suggestions for future research are discussed. 

PMID- 25767902
TI  - Single carbon nanotube-based reversible regulation of biological motor activity.
AB  - Because of their small size and high thermal conductivity, carbon nanotubes
      (CNTs) are excellent candidates for exploring heat transfer at the level of
      individual molecules in biological research. With a view toward examining the
      thermal regulation of single biomolecules, we here developed single CNTs as a new
      platform for observing the motile activity of myosin motors. On multiwall CNTs
      (diameter ~170 nm; length ~10 MUm) coated with skeletal-muscle myosin, the ATP
      driven sliding of single actin filaments was clearly observable. The normal
      sliding speed was ~6 MUm/s. Locally irradiating one end of the CNT with a red
      laser (642 nm), without directly irradiating the active myosin motors,
      accelerated the sliding speed to ~12 MUm/s, indicating the reversible activation
      of protein function on a single CNT in real time. The temperature along the CNT,
      which was estimated from the temperature-dependence of the sliding speed,
      decreased with the distance from the irradiated spot. Using these results with
      the finite element method, we calculated a first estimation of the thermal
      conductivity of multiwall CNTs in solution, as 1540 +/- 260 (Wm(-1) K(-1)), which
      is consistent with the value estimated from the width dependency of multiwall
      CNTs and the length dependency of single-wall CNTs in a vacuum or air. The
      temporal regulation of local temperature through individual CNTs should be
      broadly applicable to the selective activation of various biomolecules in vitro
      and in vivo. 

PMID- 25767903
TI  - Complete mitochondrial genome sequence of black mustard (Brassica nigra; BB) and
      comparison with Brassica oleracea (CC) and Brassica carinata (BBCC).
AB  - Crop species of Brassica (Brassicaceae) consist of three monogenomic species and
      three amphidiploid species resulting from interspecific hybridizations among
      them. Until now, mitochondrial genome sequences were available for only five of
      these species. We sequenced the mitochondrial genome of the sixth species,
      Brassica nigra (nuclear genome constitution BB), and compared it with those of
      Brassica oleracea (CC) and Brassica carinata (BBCC). The genome was assembled
      into a 232 145 bp circular sequence that is slightly larger than that of B.
      oleracea (219 952 bp). The genome of B. nigra contained 33 protein-coding genes,
      3 rRNA genes, and 17 tRNA genes. The cox2-2 gene present in B. oleracea was
      absent in B. nigra. Although the nucleotide sequences of 52 genes were identical
      between B. nigra and B. carinata, the second exon of rps3 showed differences
      including an insertion/deletion (indel) and nucleotide substitutions. A PCR test
      to detect the indel revealed intraspecific variation in rps3, and in one line of
      B. nigra it amplified a DNA fragment of the size expected for B. carinata. In
      addition, the B. carinata lines tested here produced DNA fragments of the size
      expected for B. nigra. The results indicate that at least two mitotypes of B.
      nigra were present in the maternal parents of B. carinata. 

PMID- 25767904
TI  - Method development and validation of arene substituted regioisomers in a
      pharmaceutical candidate by high temperature GC-FID.
AB  - This paper describes the development and validation of a high temperature gas
      chromatography flame ionization detection (HTGC-FID) method for the purity
      evaluation of arene substituted regioisomers in a key starting material of a
      pharmaceutical candidate in Phase 3 studies. The chromatographic conditions of
      the method employ a (5%-phenyl)-methylpolysiloxane packed column (30m*0.25mm) at
      a constant flow of 1.0mLmin(-1) with a gradient temperature program from 150
      degrees C to 400 degrees C with injector and detector temperatures of 300 degrees
      C and 340 degrees C, respectively. The calibration curve for the desired product
      (r=0.9999) was assessed for five points in the range from approximately 1.0MUgmL(
      1) to 40MUgmL(-1). The precision (% RSD) of the method was calculated for six
      replicate injections and found to be 0.81%. The limits of detection and
      quantitation were determined to be 0.06 and 0.20MUgmL(-1), respectively.

PMID- 25767905
TI  - Quantitation of pregabalin in dried blood spots and dried plasma spots by
      validated LC-MS/MS methods.
AB  - In this paper, novel LC-MS/MS methods for the determination of antiepileptic drug
      pregabalin in dried matrix spots (DMS) are presented. This attractive technique
      of sample collection in micro amount was utilized in the form of dried blood
      spots (DBS) and dried plasma spots (DPS). Following a pre-column derivatization
      procedure, using n-propyl chloroformate in the presence of n-propanol, and
      consecutive liquid-liquid extraction, derivatized pregabalin and its internal
      standard, 4-aminocyclohexanecarboxylic acid, were detected in positive ion mode
      by applying two SRM transitions per analyte. A YMC-Pack Octyl column (50mm*4.0mm,
      3MUm particle size) maintained at 30 degrees C, was utilized with running mobile
      phase composed of acetonitrile: 0.15% formic acid (85:15, v/v). Flow rate was
      550MUL/min and total run time 2min. Established methods were fully validated over
      the concentration range of 0.200-20.0MUg/mL for DBS and 0.400-40.0MUg/mL for DPS,
      respectively, while specificity, accuracy, precision, recovery, matrix-effect,
      stability, dilution integrity and spot homogeneity were found within acceptance
      criteria. Validated methods were applied for the determination of pregabalin
      levels in dried blood and plasma samples obtained from patients with epilepsy,
      after per os administration of commercial capsules. Comparison of drug level in
      blood and plasma, as well as correction steps undertaken in order to overcome
      hematocrit issue, when analyzing DBS, are also given.

PMID- 25767906
TI  - Identification of ginsenoside markers from dry purified extract of Panax ginseng
      by a dereplication approach and UPLC-QTOF/MS analysis.
AB  - A dry purified extract of Panax ginseng (PEG) was prepared using a manufacturing
      process that includes column chromatography, acid hydrolysis, and an enzyme
      reaction. During the manufacturing process, the more polar ginsenosides were
      altered into less polar forms via cleavage of their sugar chains and structural
      modifications of the aglycones, such as hydroxylation and dehydroxylation. The
      structural changes of ginsenosides during the intermediate steps from dried
      ginseng extract (DGE) to PEG were monitored by ultra-performance liquid
      chromatography coupled with quadrupole time-of-flight mass spectroscopy (UPLC
      QTOF/MS). 22 ginsenosides isolated from PEG were used as the reference standards
      for determining of unknown ginsenosides and further suggesting of the metabolic
      markers. The elution order of 22 ginsenosides based on the type of aglycones, and
      the location and number of sugar chains can be used for the structural
      elucidation of unknown ginsenosides. This information could be used in a
      dereplication process for quick and efficient identification of ginsenoside
      derivatives in ginseng preparations. A dereplication approach helped the
      identification of the metabolic markers in the UPLC-QTOF/MS chromatograms during
      the conversion process with multivariate analyses, including principal component
      analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS
      DA) plots. These metabolic markers were identified by comparing with the
      dereplication information of the reference standards of 22 ginsenosides, or they
      were assigned using the pattern of the MS/MS fragmented ions. Consequently, the
      developed metabolic profiling approach using UPLC-QTOF/MS and multivariate
      analysis represents a new method for providing quality control as well as useful
      criteria for a similarity evaluation of the manufacturing process of ginseng
      preparations.

PMID- 25767907
TI  - Using in situ Raman spectroscopy to study the drug precipitation inhibition and
      supersaturation mechanism of Vitamin E TPGS from self-emulsifying drug delivery
      systems (SEDDS).
AB  - We are reporting a new methodology of using Raman spectroscopy for studying the
      drug surfactant interactions in self-emulsifying drug delivery systems (SEDDS).
      The physicochemical properties of surfactants could affect the performance of
      drugs from lipid delivery systems. Thus the purpose of our research was to study
      the drug surfactant interactions on a molecular level to understand the mechanism
      of supersaturation and precipitation inhibition. Two surfactants, Labrasol(r) and
      Vitamin E TPGS, were used to formulate several SEDDS. The optimized SEDDS were
      further evaluated by a kinetic solubility study and in situ Raman spectroscopy
      for two model drugs. It was found that both drugs precipitated from Labrasol(r)
      SEDDS whereas TPGS was able to inhibit precipitation and achieve high drug
      supersaturation levels. In situ Raman spectroscopy indicated that hydrogen
      bonding with TPGS was the main factor responsible for inhibiting precipitation.
      This study was able to correlate the structure and physicochemical properties of
      the drugs and surfactants to their ability to prevent drug precipitation. Our
      study brings up a possible new systematic approach by using Raman spectroscopy in
      the development and optimization of lipid based delivery systems.

PMID- 25767908
TI  - Development and validation of a simple UHPLC-MS/MS method for the simultaneous
      determination of trimethylamine N-oxide, choline, and betaine in human plasma and
      urine.
AB  - A simple, sensitive, and precise ultra-high performance liquid chromatography
      tandem mass spectrometry method was developed and validated for the simultaneous
      determination of trimethylamine N-oxide, choline, and betaine in human plasma and
      urine. Sample preparation involved protein precipitation with methanol containing
      internal standards. Chromatographic separation was achieved using an Acquity BEH
      Amide (2.1mm*50mm, 1.7MUm) analytical column with gradient elution of solvent A
      (10mM ammonium formate, pH 3.5) and solvent B (acetonitrile). The flow rate was
      0.4mL/min and the total run time was 5min. Detection of analytes was performed
      using heated electrospray ionization (positive mode) and selected reaction
      monitoring. Excellent linearity was observed over the standard curve
      concentration ranges of 0.010-5.00MUg/mL (plasma) and 1.00-150MUg/mL (urine) for
      all analytes. The intra- and inter-day accuracy and precision for all quality
      controls were within +/-10%. Excellent recovery was observed. The method is
      rapid, accurate and reproducible, and was successfully applied to a pilot study
      of markers of atherosclerosis in patients with kidney disease who underwent
      successful kidney transplantation.

PMID- 25767909
TI  - Quantitative structure-retention relationships of cannabimimetic aminoalkilindole
      derivatives and their metabolites.
AB  - Development of chromatographic analyses of synthetic cannabinoids is complicated
      by the lack of commercial reference standards, especially for new analogues
      introduced in the clandestine market to bypass legal controls and for their
      metabolites. In the present work, we explore the possibility of predicting the
      retention behaviour of the cannabimimetic aminoalkilindoles and their urinary
      metabolites in high-performance liquid-chromatography using a quantitative
      structure-retention relationship (QSRR) generated by multilinear regression. To
      represent the structure of the 43 investigated analytes, 617 computational
      molecular descriptors are subjected to genetic algorithm variable selection aimed
      at identifying a small but informative subset. Predictive performance of the QSRR
      model is evaluated on an external set consisting of 10 representative compounds,
      including both drugs and their metabolites, and, successively by a Monte Carlo
      validation method. The best QSRR model, based on six molecular descriptors,
      exhibits a promising predictive performance and robustness.

PMID- 25767911
TI  - Identification of total reversible cysteine oxidation in an atherosclerosis model
      using a modified biotin switch assay.
AB  - Oxidative stress due to the imbalance of reactive oxygen species (ROS) and the
      resulting reversible cysteine oxidation (CysOX) are involved in the early
      proatherogenic aspect of atherosclerosis. Given that the corresponding redox
      signaling pathways are still unclear, a modified biotin switch assay was
      developed to quantify the reversible CysOX in an atherosclerosis model
      established by using a monocytic cell line treated with platelet releasate. The
      accumulation of ROS was observed in the model system and validated in human
      primary monocytes. Through the application of the modified biotin switch assay,
      we obtained the first reversible CysOX proteome for this model. A total of 75
      peptides, corresponding to 53 proteins, were quantified with oxidative
      modification. The bioinformatics analysis of these CysOX-containing proteins
      highlighted biological processes including glycolysis, cytoskeleton arrangement,
      and redox regulation. Moreover, the reversible oxidation of three glycolysis
      enzymes was observed using this method, and the regulation influence was verified
      by an enzyme activity assay. NADPH oxidase (NOX) inhibition treatment, in
      conjunction with the modified biotin switch method, was used to evaluate the
      global CysOX status. In conclusion, this versatile modified biotin switch assay
      provides an approach for the quantification of all reversible CysOX and for the
      study of redox signaling in atherosclerosis as well as in diseases in other
      biological systems. 

PMID- 25767910
TI  - Common and Dissociable Dysfunction of the Reward System in Bipolar and Unipolar
      Depression.
AB  - Unipolar and bipolar depressive episodes have a similar clinical presentation
      that suggests common dysfunction of the brain's reward system. Here, we evaluated
      the relationship of both dimensional depression severity and diagnostic category
      to reward system function in both bipolar and unipolar depression. In total, 89
      adults were included, including 27 with bipolar depression, 25 with unipolar
      depression, and 37 healthy comparison subjects. Subjects completed both a
      monetary reward task and a resting-state acquisition during 3T BOLD fMRI. Across
      disorders, depression severity was significantly associated with reduced
      activation for wins compared with losses in bilateral ventral striatum, anterior
      cingulate cortex, posterior cingulate cortex, and right anterior insula. Resting
      state connectivity within this reward network was also diminished in proportion
      to depression severity, most notably connectivity strength in the left ventral
      striatum. In addition, there were categorical differences between patient groups:
      resting-state connectivity at multiple reward network nodes was higher in bipolar
      than in unipolar depression. Reduced reward system task activation and resting
      state connectivity therefore appear to be a brain phenotype that is dimensionally
      related to depression severity in both bipolar and unipolar depression. In
      contrast, categorical differences in reward system resting connectivity between
      unipolar and bipolar depression may reflect differential risk of mania. Reward
      system dysfunction thus represents a common brain mechanism with relevance that
      spans categories of psychiatric diagnosis. 

PMID- 25767912
TI  - Interventions for improving community ambulation in individuals with stroke.
AB  - BACKGROUND: Community ambulation refers to the ability of a person to walk in
      their own community, outside of their home and also indoors in private or public
      locations. Some people choose to walk for exercise or leisure and may walk with
      others as an important aspect of social functioning. Community ambulation is
      therefore an important skill for stroke survivors living in the community whose
      walking ability has been affected. OBJECTIVES: To determine: (1) whether
      interventions improve community ambulation for stroke survivors, and (2) if any
      specific intervention method improves community ambulation more than other
      interventions. SEARCH METHODS: We searched the Cochrane Stroke Group Trials
      Register (September 2014), the Cochrane Central Register of Controlled Trials
      (CENTRAL) (November 2013), PubMed (1946 to November 2013), EMBASE (1980 to
      November 2013), CINAHL (1982 to November 2013), PsycINFO (1887 to November 2013),
      Scopus (1960 to November 2013), Web of Science (1900 to November 2013),
      SPORTDiscus (1975 to November 2013), and PEDro, CIRRIE and REHABDATA (November
      2013). We also searched ongoing trials registers (November 2013) and reference
      lists, and performed a cited reference search. SELECTION CRITERIA: Selection
      criteria included parallel-group randomised controlled trials (RCTs) and cross
      over RCTs, studies in which participants are adult (aged 18 years or more) stroke
      survivors, and interventions that were aimed at improving community ambulation.
      We defined the primary outcome as participation; secondary outcomes included
      activity level outcomes related to gait and self-efficacy. DATA COLLECTION AND
      ANALYSIS: One review author independently screened titles. Two review authors
      screened abstracts and full text articles, with a third review author was
      available to resolve any disagreements. Two review authors extracted data and
      assessed risk of bias. All outcomes were continuous. The analysis for the primary
      outcome used the generic inverse variance methods for meta-analysis, using the
      standardised mean difference (SMD) and standard error (SE) from the participation
      outcomes. Analyses for secondary outcomes all used SMD or mean difference (MD).
      We completed analyses for each outcome with all studies, and by type of community
      ambulation intervention (community or outdoor ambulation practice, virtual
      practice, and imagery practice). We considered trials for each outcome to be of
      low quality due to some trial design considerations, such as who knew what group
      the participants were in, and the number of people who dropped out of the
      studies. MAIN RESULTS: We included five studies involving 266 participants (136
      intervention; 130 control). All participants were adult stroke survivors, living
      in the community or a care home. Programmes to improve community ambulation
      consisted of walking practice in a variety of settings and environments in the
      community, or an indoor activity that mimicked community walking (including
      virtual reality or mental imagery). Three studies were funded by government
      agencies, and two had no funding.From two studies of 198 people there was low
      quality evidence for the effect of intervention on participation compared with
      control (SMD, 0.08, 95% confidence interval (CI) -0.20 to 0.35 (using inverse
      variance). The CI for the effect of the intervention on gait speed was wide and
      does not exclude no difference (MD 0.12, 95% CI -0.01 to 0.24; four studies, 98
      participants, low quality evidence). We considered the quality of the evidence to
      be low for all the remaining outcomes in our review: Community Walk Test (MD 
      6.35, 95% CI -21.59 to 8.88); Walking Ability Questionnaire (MD 0.53, 95% CI 
      5.59 to 6.66); Six-Minute Walk Test (MD 39.62 metres, 95% CI -8.26 to 87.51) and
      self-efficacy (SMD 0.32, 95% CI -0.09 to 0.72). We downgraded the quality of the
      evidence because of a high risk of bias and imprecision. AUTHORS' CONCLUSIONS:
      There is currently insufficient evidence to establish the effect of community
      ambulation interventions or to support a change in clinical practice. More
      research is needed to determine if practicing outdoor or community walking will
      improve participation and community ambulation skills for stroke survivors living
      in the community.

PMID- 25767913
TI  - Identification of genes involved in the drought adaptation and recovery in
      Portulaca oleracea by differential display.
AB  - Portulaca oleracea is one of the richest plant sources of omega-3 and omega-6
      fatty acids and other compounds potentially valuable for nutrition. It is broadly
      established in arid, semiarid and well-watered fields, thus making it a promising
      candidate for research on abiotic stress resistance mechanisms. It is capable of
      withstanding severe drought and then of recovering upon rehydration. Here, the
      adaptation to drought and the posterior recovery was evaluated at transcriptomic
      level by differential display validated by qRT-PCR. Of the 2279 transcript
      derived fragments amplified, 202 presented differential expression. Ninety of
      them were successfully isolated and sequenced. Selected genes were tested against
      different abiotic stresses in P. oleracea and the behavior of their orthologous
      genes in Arabidopsis thaliana was also explored to seek for conserved response
      mechanisms. In drought adapted and in recovered plants changes in expression of
      many protein metabolism-, lipid metabolism- and stress-related genes were
      observed. Many genes with unknown function were detected, which also respond to
      other abiotic stresses. Some of them are also involved in the seed
      desiccation/imbibition process and thus would be of great interest for further
      research. The potential use of candidate genes to engineer drought tolerance
      improvement and recovery is discussed.

PMID- 25767914
TI  - Fungal and bacterial metabolites associated with natural contamination of locally
      processed rice (Oryza sativa L.) in Nigeria.
AB  - This study reports the fungal and bacterial metabolites associated with natural
      contamination of 38 composite samples of locally processed rice from five agro
      ecological zones of Nigeria (AEZs). The samples were evaluated for the presence
      of microbial metabolites by LC-MS/MS. Among the identified metabolites, 63 fungal
      and 5 bacterial metabolites were measured at varying concentrations and
      occurrence levels. Fusarium toxins had the highest incidence of 79%, but occurred
      in low amounts with fumonisin B1 (FB1) having the highest percentage incidence of
      39.5% and a mean of 18.5 ug/kg. Among the Aspergillus toxins, aflatoxins (AFs)
      occurred in 36.9% of the rice samples, with aflatoxin B1 (AFB1) having the
      highest occurrence level of 18.4% and a mean value of 5 ug/kg. About 12
      metabolites had incidence levels > 50%, including beauvericin (BEA) and
      tryptophol, which had occurrence levels of 100%. Among the emerging toxins under
      evaluation by international organisations such as the European Food Safety
      Authority (EFSA) and the Food and Agriculture Organisation of the United Nations
      (FAO), citrinin, sterigmatocystin (STER) and beauvericin were detected with
      maximum values of 207, 125 and 131 MUg/kg, respectively. This paper also reports
      the first documented evidence of the contamination of Nigerian rice by bacterial
      and Alternaria metabolites, nivalenol, kojic acid, STER, moniliformin, fusaric
      acid, fumonisin B3, citrinin, 3-nitropropionic acid, andrastin A, cytochalasins,
      emodin and physicon.

PMID- 25767915
TI  - Simultaneous analysis of zolpidem and its metabolite in whole blood and oral
      fluid samples by SPE-LC/MS for clinical and forensic purposes.
AB  - PURPOSE: The new analytical method of qualitative and quantitative determination
      of zolpidem and qualitative analysis of its main metabolite in blood and oral
      fluid samples was developed. MATERIALS AND METHODS: Sample preparation was
      carried out using a polymeric ion-exchange sorbent in solid phase extraction
      (SPE). Analysis was realized using liquid chromatography with mass spectrometry
      detection (LC/MS). The method was validated in terms of few parameters. LOD, LOQ,
      linearity, precision, selectivity, ion suppression and stability were estimated.
      RESULTS: Obtained method showed good linearity with determination coefficient
      (R(2)) of 0.9989 and 0.9998 for blood and oral fluid samples, respectively. LOD
      and LOQ of zolpidem were 0.2ng/mL and 1.0ng/mL, respectively, for both blood and
      oral fluid samples. SPE method recovery varies from 79.9+/-12.6 to 104.1+/-1.77
      for blood sample and 80.2+/-0.48 to 103.8+/-1.51 for oral fluid sample. Samples
      collected from patients taking zolpidem with a prescription were analyzed.
      Detection of zolpidem was possible after 15h from ingestion of 10mg zolpidem
      tartrate in both types of samples. CONCLUSION: The developed method allows
      quantitation of zolpidem in therapeutic and subtherapeutic range as well as
      qualitative analysis of its main metabolite in blood and oral fluid samples. This
      method meets criteria required for bioanalytical applications and can be used for
      clinical and forensic purposes.

PMID- 25767916
TI  - Surface plasmon coupled metal enhanced spectral and charge transport properties
      of poly(3,3'''-dialkylquarterthiophene) Langmuir Schaefer films.
AB  - The coupling of organic molecule excitons with metal nano-structure surface
      plasmons can improve the performance of optoelectronic devices. This paper
      presents the effect of localized silver metal surface plasmons on spectral as
      well as charge transport properties of ordered molecular Langmuir Schaefer (LS)
      films of a fluorescent conducting multifunctional organic polymer: poly (3,3'''
      dialkylquarterthiophene) [PQT-12]. The stability and thickness of the PQT-12 LS
      film were studied by the pressure vs. area isotherm curve. Atomic force
      microscopy images indicate the formation of a smooth ordered polymer thin LS film
      of PQT-12 over silver nanostructure island films [SNIF] (~40 to 50 nm in size).
      Raman, electronic absorption and fluorescence spectral measurements of the PQT-12
      LS film, near SNIF i.e. the near field, show a plasmon coupled enhancement of ~13
      fold in the intensity of Raman bands along with a two-fold enhancement in the
      absorption band (531 nm) and a six-fold enhancement in the fluorescence band (665
      nm) coupled with a decrease in fluorescence decay time with improved
      photostability as compared to an identical control sample containing no SNIF i.e.
      the far field condition. These results indicate the formation of a plasmon
      coupled unified fluorophore system due to adsorption of the PQT-12 LS film over
      SNIF. The effect of plasmonic coupling is also studied by applying an electric
      field in sandwiched structures of Al/PQT-12 LS/SNIF/ITO with respect to Al/PQT-12
      LS/ITO. Nearly three orders of magnitude enhancement in the current density (J-V
      plot) of the PQT-12 LS film is observed in the presence of SNIF, which further
      increases, on illuminating the film by green laser light [532 nm], while the
      fluorescence intensity and decay time decrease. X-ray photoelectron spectroscopic
      measurements of SNIF also show a red shift in 3d3/2 and 3d5/2 transitions of
      silver in the PQT-12 coated LS film, which indicates partial charge transfer from
      the PQT-12 polymer backbone to SNIF and causes an enhancement in conductivity.
      This again supports the formation of a field controlled radiating plasmon coupled
      fluorophore unified system. These findings show greater potential in developing a
      voltage controlled high photon flux electroluminescent material for multifarious
      applications.

PMID- 25767917
TI  - Feasibility of protein turnover studies in prototroph Saccharomyces cerevisiae
      strains.
AB  - Quantitative proteomics studies of yeast that use metabolic labeling with amino
      acids rely on auxotrophic mutations of one or more genes on the amino acid
      biosynthesis pathways. These mutations affect yeast metabolism and preclude the
      study of some biological processes. Overcoming this limitation, it has recently
      been described that proteins in a yeast prototrophic strain can also be
      metabolically labeled with heavy amino acids. However, the temporal profiles of
      label incorporation under the different phases of the prototroph's growth have
      not been examined. Labeling trajectories are important in the study of protein
      turnover and dynamics, in which label incorporation into proteins is monitored
      across many time points. Here we monitored protein labeling trajectories for 48 h
      after a pulse with heavy lysine in a yeast prototrophic strain and compared them
      with those of a lysine auxotrophic yeast. Labeling was successful in prototroph
      yeast during exponential growth phase but not in stationary phase. Furthermore,
      we were able to determine the half-lives of more than 1700 proteins during
      exponential phase of growth with high accuracy and reproducibility. We found a
      median half-life of 2 h in both strains, which corresponds with the cellular
      doubling time. Nucleolar and ribosomal proteins showed short half-lives, whereas
      mitochondrial proteins and other energy production enzymes presented longer half
      lives. Except for some proteins involved in lysine biosynthesis, we observed a
      high correlation in protein half-lives between prototroph and auxotroph strains.
      Overall, our results demonstrate the feasibility of using prototrophs for
      proteomic turnover studies and provide a reliable data set of protein half-lives
      in exponentially growing yeast. 

PMID- 25767918
TI  - Drug-induced death of eosinophils. Promises and pitfalls.

PMID- 25767919
TI  - Lost in translation: failure of tracheal tube modifications to impact ventilator
      associated pneumonia.

PMID- 25767920
TI  - What the genetics "RTEL"ing us about telomeres and pulmonary fibrosis.

PMID- 25767921
TI  - Can particulate pollution affect lung function in healthy adults?

PMID- 25767922
TI  - The imitation game in pulmonary arterial hypertension. Sex, bone morphogenetic
      protein receptor, and the estrogen paradox.

PMID- 25767923
TI  - New therapy for apnea of prematurity?

PMID- 25767924
TI  - Muscle dysfunction in patients with lung diseases: a growing epidemic.

PMID- 25767925
TI  - Rapidly progressive pulmonary hypertension in a patient with pulmonary tumor
      thrombotic microangiopathy.

PMID- 25767926
TI  - Orenitram . . . not verified.

PMID- 25767927
TI  - Airway epithelium defects and risks of allergic diseases: multiple associations
      revealed by a biomarker study among adolescents.

PMID- 25767928
TI  - An alternative perspective regarding the "myth of the workforce crisis".

PMID- 25767929
TI  - Intensivist workforce in the United States: the crisis is real, not imagined.

PMID- 25767930
TI  - Reply: "An alternative perspective regarding the 'myth of the workforce crisis'"
      and "Intensivist workforce in the United States: the crisis is real, not
      imagined".

PMID- 25767931
TI  - Comment on article entitled: "PLAY Project Home Consultation intervention program
      for young children with autism spectrum disorders: a randomized controlled
      trial".

PMID- 25767932
TI  - Do pediatricians recognize fetal alcohol spectrum disorders in children with
      developmental and behavioral problems?
AB  - OBJECTIVE: Limited studies have examined pediatricians' knowledge, attitudes, and
      practice about fetal alcohol spectrum disorders (FASDs), and none have examined
      alcohol-related neurodevelopmental disabilities (ARND). This study examined
      whether pediatricians consider FASDs in children with developmental and
      behavioral problems. METHODS: All 149 pediatricians, 55 males and 94 females, in
      New Haven County, CT, were contacted to complete a web-based survey. They were
      given cases of preschool boys with (1) fetal alcohol syndrome (FAS), (2) ARND,
      and (3) Williams Syndrome (WS) and asked to provide a diagnosis and rate their
      confidence in this. They could access up to 7 additional pieces of information.
      RESULTS: Sixty-six pediatricians responded (44.3%), and 46 had complete data
      (30.9%). Eight (17.4%) correctly identified FAS and 29 (63.1%) ARND.
      Significantly fewer pediatricians diagnosed FAS versus ARND and WS (p < .001),
      and they were less confident in identifying FAS and ARND than WS (10.9 % and
      45.7% vs. 73.9%, p < .01). After viewing the photographs with sentinel
      dysmorphology and case description, respondents were more likely to diagnose WS
      (37%) versus FAS (19.6%) (p = .064), less confident in their diagnosis (p =
      .009), and required more information to make an FAS diagnosis (p = .002).
      CONCLUSIONS: Pediatricians underrecognize FASDs, lack confidence in making this
      diagnosis, and are unfamiliar with the diagnostic criteria. They need more
      training to consider the possibility of an FASD when seeing children with
      developmental and behavioral problems.

PMID- 25767934
TI  - Magnetic ordering and anisotropy in heavy atom radicals.
AB  - Recent developments in stable radical chemistry have afforded "heavy atom"
      radicals, neutral open-shell (S = 1/2) molecular species containing heavy p-block
      elements (S, Se), which display solid-state magnetic properties once considered
      exclusive to conventional metal-based magnets. These highly spin-delocalized
      radicals do not associate in the solid state and yet display extensive networks
      of close intermolecular interactions. Spin density on the heavy atoms allows for
      increased isotropic and spin-orbit mediated anisotropic exchange effects.
      Structural variations induced by chemical modification and physical pressure,
      coupled with ab-initio methods to estimate exchange energies, have facilitated
      the development of predictive structure/property relationships. These results,
      coupled with detailed theoretical analyses and magnetic resonance spectroscopic
      measurements, have provided insight into the magnetic structure of ferromagnetic
      and spin-canted antiferromagnetic ordered materials as well as an understanding
      of the importance of spin-orbit coupling contributions to magnetic hysteresis and
      anisotropy. Isotropic and anisotropic ferromagnetic exchange can also be enhanced
      indirectly by the incorporation of heavy atoms into nonspin-bearing sites, where
      they can contribute to multi-orbital spin-orbit coupling. 

PMID- 25767935
TI  - Monte Carlo calculation of specific absorbed fractions: variance reduction
      techniques.
AB  - The purpose of the present work is to calculate specific absorbed fractions using
      variance reduction techniques and assess the effectiveness of these techniques in
      improving the efficiency (i.e. reducing the statistical uncertainties) of
      simulation results in cases where the distance between the source and the target
      organs is large and/or the target organ is small. The variance reduction
      techniques of interaction forcing and an ant colony algorithm, which drives the
      application of splitting and Russian roulette, were applied in Monte Carlo
      calculations performed with the code penelope for photons with energies from 30
      keV to 2 MeV. In the simulations we used a mathematical phantom derived from the
      well-known MIRD-type adult phantom. The thyroid gland was assumed to be the
      source organ and urinary bladder, testicles, uterus and ovaries were considered
      as target organs. Simulations were performed, for each target organ and for
      photons with different energies, using these variance reduction techniques, all
      run on the same processor and during a CPU time of 1.5 . 10(5) s. For energies
      above 100 keV both interaction forcing and the ant colony method allowed reaching
      relative uncertainties of the average absorbed dose in the target organs below 4%
      in all studied cases. When these two techniques were used together, the
      uncertainty was further reduced, by a factor of 0.5 or less. For photons with
      energies below 100 keV, an adapted initialization of the ant colony algorithm was
      required. By using interaction forcing and the ant colony algorithm, realistic
      values of the specific absorbed fractions can be obtained with relative
      uncertainties small enough to permit discriminating among simulations performed
      with different Monte Carlo codes and phantoms. The methodology described in the
      present work can be employed to calculate specific absorbed fractions for
      arbitrary arrangements, i.e. energy spectrum of primary radiation, phantom model
      and source and target organs.

PMID- 25767936
TI  - Computations on the primary photoreaction of Br2 with CO2: stepwise vs concerted
      addition of Br atoms.
AB  - It was proposed previously that Br2-sensitized photolysis of liquid CO2 proceeds
      through a metastable primary photoproduct, CO2Br2. Possible mechanisms for such a
      photoreaction are explored here computationally. First, it is shown that the
      CO2Br radical is not stable in any geometry. This rules out a free-radical
      mechanism, for example, photochemical splitting of Br2 followed by stepwise
      addition of Br atoms to CO2-which in turn accounts for the lack of previously
      observed Br2+CO2 photochemistry in gas phases. A possible alternative mechanism
      in liquid phase is formation of a weakly bound CO2:Br2 complex, followed by
      concerted photoaddition of Br2. This hypothesis is suggested by the previously
      published spectroscopic detection of a binary CO2:Br2 complex in the
      supersonically cooled gas phase. We compute a global binding-energy minimum of 
      6.2 kJ mol(-1) for such complexes, in a linear geometry. Two additional local
      minima were computed for perpendicular (C2v) and nearly parallel asymmetric
      planar geometries, both with binding energies near -5.4 kJ mol(-1). In these two
      latter geometries, C-Br and O-Br bond distances are simultaneously in the range
      of 3.5-3.8 A, that is, perhaps suitable for a concerted photoaddition under the
      temperature and pressure conditions where Br2 + CO2 photochemistry has been
      observed. 

PMID- 25767937
TI  - Direct ortho-C-H functionalization of aromatic alcohols masked by acetone oxime
      ether via exo-palladacycle.
AB  - A simple and practical exo-oxime ether auxilixary for ortho-C-H functionalization
      of aromatic alcohols has been developed. Selective olefination of aromatic
      alcohols were first achieved via a six- or seven-membered exo-acetone oxime ether
      palladacycle with broad substrate scope. In addition, the crystal of the exo
      palladacycle intermediate was obtained for the first time, and the application of
      this method in total synthesis of 3-deoxyisoochracinic acid was accomplished via
      a novel retro-synthetic disconnection approach, thus demonstrating the utility of
      this transformation. 

PMID- 25767938
TI  - Impact of three-dimensional imaging in acquisition of laparoscopic skills in
      novice operators.
AB  - BACKGROUND: Three-dimensional (3D) laparoscopes have been developed to maintain
      the perception of depth in the operating field. Two-dimensional (2D) imaging
      relies on tactile feedback, visual cues, and previous experience. The aim of this
      study was to test if 3D laparoscopic vision is superior to 2D laparoscopic vision
      in training novice operators in completing set laparoscopic tasks. MATERIALS AND
      METHODS: The study population consisted of 20 interns and medical students. The
      participants were randomized to completing tasks using a 2D or 3D system. These
      included pegboard transfer (PT), continuous suturing (CS), and intracorporeal
      knot-tying (IK). The time to complete the task and number of errors made were
      recorded. RESULTS: Following adjustment for potential confounders, time to
      complete CS and IK was significantly longer among participants who used the 2D
      laparoscope compared with those who used the 3D laparoscope (CS, P<.0001; IK,
      P<.0001). This same effect was not demonstrated in time to perform PT (PT,
      P=.04). The 2D laparoscope was associated with a significant increase in the
      number of errors on the IK task (P<.0001) but not on the PT or CS tasks (PT,
      P=.35; CS, P=.26). CONCLUSIONS: The 3D system assists novice operators perform
      more complex laparoscopic tasks in a decreased amount of time and with fewer
      errors.

PMID- 25767939
TI  - Asymmetric total synthesis of Apocynaceae hydrocarbazole alkaloids (+)
      deethylibophyllidine and (+)-limaspermidine.
AB  - An unprecedented asymmetric catalytic tandem aminolysis/aza-Michael addition
      reaction of spirocyclic para-dienoneimides has been designed and developed
      through organocatalytic enantioselective desymmetrization. A unified strategy
      based on this key tandem methodology has been divergently explored for the
      asymmetric total synthesis of two natural Apocynaceae alkaloids, (+)
      deethylibophyllidine and (+)-limaspermidine. The present studies not only enrich
      the tandem reaction design concerning the asymmetric catalytic assembly of a
      chiral all-carbon quaternary stereocenter contained in the densely functionalized
      hydrocarbazole synthons but also manifest the potential for the application of
      the asymmetric catalysis based on the para-dienone chemistry in asymmetric
      synthesis of natural products. 

PMID- 25767940
TI  - Unilateral streak ovary in Turner syndrome.

PMID- 25767941
TI  - Ebola in pregnancy: have we learned any lessons?

PMID- 25767942
TI  - Mid-trimester maternal serum AFP and hCG as markers of preterm and term adverse
      pregnancy outcomes.
AB  - OBJECTIVE: To evaluate the predictive values of mid-trimester serum alpha
      fetoprotein (AFP) and human chorionic gonadotropin (hCG) for preterm and term
      placenta-mediated adverse pregnancy outcomes (PMAPOs). METHODS: We extracted data
      for nulliparous women with a singleton pregnancy without aneuploidy or lethal
      fetal anomalies from a prospective cohort study. Maternal serum AFP and hCG
      measured between 13 and 17 weeks of gestation and expressed as multiples of the
      median (MoM) for gestational age were compared between women who developed a
      PMAPO (preeclampsia, intrauterine growth restriction, fetal death) before term or
      at term and women who did not develop any of these complications. RESULTS: Among
      3466 nulliparous women, maternal serum AFP and hCG levels were available in 2110
      and 2125 cases, respectively. Women who developed a PMAPO before term had a
      higher median level of serum AFP (1.4 vs. 1.1 MoM; P < 0.01) and hCG (1.3 vs. 1.1
      MoM; P < 0.01) than controls. A serum hCG > 2.0 MoM was associated with a higher
      risk of PMAPO before term (RR 4.6; CI 95% 2.3 to 9.1) but had no impact on the
      risk of PMAPO at term (RR 1.1; CI 95% 0.7 to 1.7). Maternal serum AFP > 2.0 MoM
      was also associated with a significant increase in the risk of preterm PMAPO (RR
      3.9; CI 95% 1.6 to 9.8) but not term PMAPO (RR 1.2; CI 95% 0.6 to 2.3).
      CONCLUSION: Maternal serum AFP or hCG > 2.0 MoM increases the risk of preterm
      PMAPO but not term PMAPO in our population. We suggest that women with elevated
      serum AFP or hCG should receive standard pregnancy care once they have reached 37
      weeks of gestation if fetal growth is in the normal range.

PMID- 25767943
TI  - A retrospective analysis of stillbirth epidemiology and risk factors among First
      Nations and non-First Nations pregnancies in Alberta from 2000 to 2009.
AB  - OBJECTIVE: Using a large administrative dataset we examined stillbirth
      epidemiology in First Nations and non-First Nations pregnancies in Alberta,
      focusing on previously unexplored longitudinal trends. METHODS: We undertook a
      retrospective analysis of de-identified data from 426 945 delivery records for
      the years 2000 to 2009. Age-adjusted prevalence of antepartum and intrapartum
      stillbirth were calculated and compared by ethnicity, as were longitudinal
      changes via average annual percent change analyses. Risk factors were explored
      via multivariable logistic regression analysis. RESULTS: Overall age-adjusted
      prevalence of antepartum and intrapartum stillbirth was significantly higher (P <
      0.001) in First Nations pregnancies than in non-First Nations pregnancies, and
      prevalence remained stable over time in both groups. Pre-existing diabetes was a
      strong predictor of stillbirth. CONCLUSION: Stillbirth prevalence remains higher
      in First Nations pregnancies than in non-First Nations. Improved awareness of pre
      existing diabetes and effective interventions are needed in First Nations women
      to decrease stillbirth risk.

PMID- 25767944
TI  - HPV awareness in higher-risk young women: the need for a targeted HPV catch-up
      vaccination program.
AB  - OBJECTIVE: To determine levels of HPV awareness and knowledge in higher-risk
      young women and their attitudes toward HPV vaccination and catch-up programs.
      METHODS: An anonymous, cross-sectional, Internet-based, self-reported
      questionnaire was completed by women ages 13 to 25 attending two outreach
      clinics. Primary outcomes were HPV infection/vaccine awareness, vaccination
      rates, and catch-up program acceptability. Chi-square, Fisher exact test, and
      logistic regression analyses were performed. RESULTS: Of 105 respondents (mean
      age 19.32), 66.7% received social assistance and 54.3% relied on walk-in clinics.
      Overall HPV awareness was 81.0% and vaccine awareness was 76.2%. HPV awareness
      was significantly higher in women < 20 years old (P = 0.032) and with past
      sexually transmitted infection (STI) history (P = 0.039) but didn't differ by
      education level. Vaccine awareness differed significantly with STI history (P =
      0.031) but not by age or education level. Awareness of HPV's association with
      genital warts and cervical cancer was low (30.0%, 41.9%) and didn't differ by
      education level or sexually transmitted infection history. Thirty percent had
      been vaccinated (of those, 42% had received 3 doses), mainly in school-based
      programs (71%). Odds of vaccination were significantly higher in those with a
      family doctor (OR 8.08). Reasons for not being vaccinated included: "Did not know
      about it"(28.5%) and "Don't know" (28.5%). Catch-up program acceptability was
      high (92.8%, 95.2% if free) and did not differ significantly by age or education
      level. CONCLUSION: Higher-risk young women may have high levels of HPV
      infection/vaccine awareness but lack knowledge of HPV consequences. Those who
      missed or did not complete HPV vaccination opportunities would support free catch
      up vaccination programs in accessible, youth-friendly centres.

PMID- 25767945
TI  - Bilateral sacrospinous vault fixation with tailored synthetic mesh arms: clinical
      outcomes at one year.
AB  - OBJECTIVES: Bilateral sacrospinous fixation with tailored mesh arms (bSSVF) uses
      polypropylene mesh to suspend the vault to the sacrospinous ligaments bilaterally
      with minimal tension, recreating nulliparous midline anatomy. It can be used with
      uterine conservation. Our primary objective was to determine objective cure rate
      at one year following bSSVF compared with a control group undergoing abdominal
      sacrocolpopexy (ASC). Secondary objectives were to compare symptoms, quality of
      life, sexual function, pain, and global satisfaction before and after surgery and
      between bSSVF and ASC groups at one year. METHODS: This prospective cohort study
      enrolled patients with symptomatic prolapse who chose to undergo bSSVF or ASC.
      Baseline demographics were obtained. Prolapse quantification, validated symptom
      questionnaire scores, and McGill pain scores were obtained at baseline, six
      weeks, and one-year postoperatively. Global satisfaction was recorded. The
      primary outcome measure was the difference in cure rate (vault stage <= 1)
      between groups. RESULTS: Fifty patients were recruited: 30 underwent bSSVF and 17
      ASC. Forty-three patients were available for one-year follow-up. Baseline data
      were similar. There was no difference in vault stage between bSSVF and ASC groups
      at one year. Five women who underwent bSSVF had cervical elongation, and four of
      these were classified as POP recurrence. Women who underwent bSSVF had more
      anterior recurrences but fewer postoperative complications, shorter hospital
      stay, and less use of narcotics than controls. Questionnaire scores were similar
      at one year. All respondents felt subjective improvement after either surgical
      procedure. CONCLUSIONS: Objective and subjective cure rates are comparable after
      bSSVF and ASC. Hysteropexy may cause cervical elongation that merits further
      research.

PMID- 25767946
TI  - The impact of qualitative research on gynaecologic oncology guidelines.
AB  - OBJECTIVE: Inherent in the care provided to patients with cancer is an important
      psychosocial element which has been explored scientifically through qualitative
      research. The purpose of our study was to evaluate the availability of
      qualitative research in gynaecologic oncology and to measure its integration in
      gynaecologic oncology practice guidelines. METHODS: We searched Medline, CINHAL,
      Scopus, and Web of Science databases to identify the availability of qualitative
      research conducted in the past 20 years on the three most prevalent gynaecologic
      cancers: endometrial, ovarian, and cervical cancer. National and international
      practice guidelines on management of gynaecologic cancers were selected using the
      National Guideline Clearinghouse website, the Society of Obstetricians and
      Gynaecologists of Canada website, and the Standards and Guidelines Evidence
      directory of cancer guidelines. Bibliometric analysis was used to determine the
      frequency of qualitative references cited in these guidelines. RESULTS: One
      hundred thirteen qualitative research papers on gynaecologic cancers were
      identified focusing on psychological impacts, social dynamics, and doctor-patient
      interactions during cancer treatment and recovery. Among the 15 national and
      international clinical practice guidelines identified on management of
      gynaecologic cancer, there were a total of 2272 references, and of these only
      three references citing qualitative research were identified (0.1%) in only one
      of the 15 practice guidelines. CONCLUSION: Although qualitative research is being
      carried out in gynaecologic oncology, its integration into clinical practice
      guidelines is essentially absent. Efforts to narrow the gap between qualitative
      research and clinical practice are essential in ensuring a comprehensive approach
      to the treatment of patients with gynaecologic cancer.

PMID- 25767947
TI  - Surgical treatment of intractable pelvic, groin, and perineal neuropathic pain in
      a gynaecologic patient: triple neurectomy.
AB  - BACKGROUND: Gynaecologists who are asked to assess patients with pain in the
      genital area are not generally trained to consider neurogenic causes for the
      pain, nor are they generally familiar with the surgical procedures that can
      eliminate this pain. CASE: A 54-year-old woman who had undergone multiple
      laparotomies for Caesarean section, abdominal hysterectomy, treatment of ovarian
      cysts, and lysis of adhesions through a transverse abdominal approach presented
      with a seven- to eight-month history of severe neuropathic left-sided groin,
      labial, and perineal pain. Neurectomy involving the iliohypogastric,
      ilioinguinal, and genitofemoral nerves was performed. Postoperatively the patient
      experienced complete resolution of the pain. CONCLUSION: Neuropathic pain should
      be considered in the differential diagnosis of women with an extensive history of
      lower abdominal surgery. Neurectomy is an effective treatment for this.

PMID- 25767948
TI  - Exposure to nitrofurantoin during early pregnancy and congenital malformations: a
      systematic review and meta-analysis.
AB  - OBJECTIVE: Because of an increased resistance of urinary pathogens to penicillin
      derivatives, nitrofurantoin is commonly used as an alternative in treating
      urinary tract infection because a wide range of both Gram negative and positive
      organisms are sensitive to it. The safety of the fetus after exposure to
      nitrofurantoin remains controversial. METHODS: We conducted a systematic review
      and meta-analysis to evaluate the fetal safety of nitrofurantoin. We searched
      Medline, EMBASE, references from published reports, and meeting abstracts for
      relevant studies. Articles were included in the review if they were human
      studies, reported pregnancy outcomes, reported the use of nitrofurantoin in the
      first trimester of pregnancy, and included a comparator group of unexposed
      pregnancies. The primary outcome was the rate of major malformations; secondary
      outcomes were rates of craniosynostosis, cleft lip or palate defects,
      cardiovascular defects, and hypoplastic left heart syndrome. RESULTS: Eight
      studies reporting on 91 115 exposed cases and 1 578 745 unexposed controls were
      included in the primary meta-analysis examining the risk of major malformation.
      Five cohort studies reported on 9275 exposed and 1 491 933 unexposed infants,
      resulting in an overall RR of 1.01 (95% CI 0.81 to 1.26); however, three case
      control studies with a total of 39 268 cases of major malformations and 129 394
      controls gave an overall OR of 1.22 (95% CI 1.02 to 1.45). No increased risk for
      cardiovascular malformations, oral cleft, or craniosynostosis was identified. For
      assessing risk of hypoplastic left heart syndrome, only three articles were
      eligible; these demonstrated an OR of 3.07 (95% CI 1.59 to 5.93). CONCLUSION:
      While no association was found between fetal exposure to nitrofurantoin and major
      malformation in cohort studies, there was a slight but significant teratogenic
      risk in case-control studies, which are more sensitive to adverse effects.

PMID- 25767949
TI  - The management of uterine leiomyomas.
AB  - OBJECTIVES: The aim of this guideline is to provide clinicians with an
      understanding of the pathophysiology, prevalence, and clinical significance of
      myomata and the best evidence available on treatment modalities. OPTIONS: The
      areas of clinical practice considered in formulating this guideline were
      assessment, medical treatments, conservative treatments of myolysis, selective
      uterine artery occlusion, and surgical alternatives including myomectomy and
      hysterectomy. The risk-to-benefit ratio must be examined individually by the
      woman and her health care provider. OUTCOMES: Implementation of this guideline
      should optimize the decision-making process of women and their health care
      providers in proceeding with further investigation or therapy for uterine
      leiomyomas, having considered the disease process and available treatment
      options, and reviewed the risks and anticipated benefits. EVIDENCE: Published
      literature was retrieved through searches of PubMed, CINAHL, and Cochrane
      Systematic Reviews in February 2013, using appropriate controlled vocabulary
      (uterine fibroids, myoma, leiomyoma, myomectomy, myolysis, heavy menstrual
      bleeding, and menorrhagia) and key words (myoma, leiomyoma, fibroid, myomectomy,
      uterine artery embolization, hysterectomy, heavy menstrual bleeding,
      menorrhagia). The reference lists of articles identified were also searched for
      other relevant publications. Results were restricted to systematic reviews,
      randomized control trials/controlled clinical trials, and observational studies.
      There were no date limits but results were limited to English or French language
      materials. Searches were updated on a regular basis and incorporated in the
      guideline to January 2014. Grey (unpublished) literature was identified through
      searching the websites of health technology assessment and health technology
      related agencies, clinical practice guideline collections, and national and
      international medical specialty societies. BENEFITS, HARMS, AND COSTS: The
      majority of fibroids are asymptomatic and require no intervention or further
      investigations. For symptomatic fibroids such as those causing menstrual
      abnormalities (e.g. heavy, irregular, and prolonged uterine bleeding), iron
      defficiency anemia, or bulk symptoms (e.g., pelvic pressure/pain, obstructive
      symptoms), hysterectomy is a definitive solution. However, it is not the
      preferred solution for women who wish to preserve fertility and/or their uterus.
      The selected treatment should be directed towards an improvement in
      symptomatology and quality of life. The cost of the therapy to the health care
      system and to women with fibroids must be interpreted in the context of the cost
      of untreated disease conditions and the cost of ongoing or repeat investigative
      or treatment modalities. VALUES: The quality of evidence in this document was
      rated using the criteria described in the Report of the Caadian Task Force on
      Preventive Health Care (Table 1). Summary Statements 1. Uterine fibroids are
      common, appearing in 70% of women by age 50; the 20% to 50% that are symptomatic
      have considerable social and economic impact in Canada. (II-3) 2. The presence of
      uterine fibroids can lead to a variety of clinical challenges. (III) 3. Concern
      about possible complications related to fibroids in pregnancy is not an
      indication for myomectomy except in women who have had a previous pregnancy with
      complications related to these fibroids. (III) 4. Women who have fibroids
      detected in pregnancy may require additional maternal and fetal surveillance. (II
      2) 5. Effective medical treatments for women with abnormal uterine bleeding
      associated with uterine fibroids include the levonorgestrel intrauterine system,
      (I) gonadotropin-releasing hormone analogues, (I) selective progesterone receptor
      modulators, (I) oral contraceptives, (II-2) progestins, (II-2) and danazol. (II
      2) 6. Effective medical treatments for women with bulk symptoms associated with
      fibroids include selective progesterone receptor modulators and gonadotropin
      releasing hormone analogues. (I) 7. Hysterectomy is the most effective treatment
      for symptomatic uterine fibroids. (III) 8. Myomectomy is an option for women who
      wish to preserve their uterus or enhance fertility, but carries the potential for
      further intervention. (II-2) 9. Of the conservative interventional treatments
      currently available, uterine artery embolization has the longest track record and
      has been shown to be effective in properly selected patients. (II-3) 10. Newer
      focused energy delivery methods are promising but lack long-term data. (III)
      Recommendations 1. Women with asymptomatic fibroids should be reassured that
      there is no evidence to substantiate major concern about malignancy and that
      hysterectomy is not indicated. (III-D) 2. Treatment of women with uterine
      leiomyomas must be individualized based on symptomatology, size and location of
      fibroids, age, need and desire of the patient to preserve fertility or the
      uterus, the availability of therapy, and the experience of the therapist. (III-B)
      3. In women who do not wish to preserve fertility and/or their uterus and who
      have been counselled regarding the alternatives and risks, hysterectomy by the
      least invasive approach possible may be offered as the definitive treatment for
      symptomatic uterine fibroids and is associated with a high level of satisfaction.
      (II-2A) 4. Hysteroscopic myomectomy should be considered first-line conservative
      surgical therapy for the management of symptomatic intracavitary fibroids. (II
      3A) 5. Surgical planning for myomectomy should be based on mapping the location,
      size, and number of fibroids with the help of appropriate imaging. (III-A) 6.
      When morcellation is necessary to remove the specimen, the patient should be
      informed about possible risks and complications, including the fact that in rare
      cases fibroid(s) may contain unexpected malignancy and that laparoscopic power
      morcellation may spread the cancer, potentially worsening their prognosis. (III
      B) 7. Anemia should be corrected prior to proceeding with elective surgery. (II
      2A) Selective progesterone receptor modulators and gonadotropin-releasing hormone
      analogues are effective at correcting anemia and should be considered
      preoperatively in anemic patients. (I-A) 8. Use of vasopressin, bupivacaine and
      epinephrine, misoprostol, peri-cervical tourniquet, or gelatin-thrombin matrix
      reduce blood loss at myomectomy and should be considered. (I-A) 9. Uterine artery
      occlusion by embolization or surgical methods may be offered to selected women
      with symptomatic uterine fibroids who wish to preserve their uterus. Women
      choosing uterine artery occlusion for the treatment of fibroids should be
      counselled regarding possible risks, including the likelihood that fecundity and
      pregnancy may be impacted. (II-3A) 10. In women who present with acute uterine
      bleeding associated with uterine fibroids, conservative management with
      estrogens, selective progesterone receptor modulators, antifibrinolytics, Foley
      catheter tamponade, and/or operative hysteroscopic intervention may be
      considered, but hysterectomy may become necessary in some cases. In centres where
      available, intervention by uterine artery embolization may be considered. (III
      B).

PMID- 25767950
TI  - SOGC committee opinion on the management of a pregnant woman exposed to or
      infected with Ebola virus disease in Canada.
AB  - OBJECTIVE: To review the evidence and provide recommendations on the general
      management of a pregnant woman exposed to or infected with Ebola virus disease
      (EVD). OUTCOMES: OUTCOMES evaluated include general principles of approach and
      specific aspects of management of EVD relevant to pregnancy. EVIDENCE: Published
      literature was retrieved through searches of Medline, EMBASE, and CINAHL in
      October 2014 using appropriate controlled vocabulary and key words (Ebola and
      pregnancy; hemorrhagic fever and pregnancy). Results were restricted to
      systematic reviews, randomized control trials/controlled clinical trials, and
      observational studies published in English. Searches were updated and
      incorporated in the guideline to November 7, 2014. Grey (unpublished) literature
      was identified through searching the websites of health technology assessment and
      health technology assessment-related agencies, clinical practice guideline
      collections, and national and international medical specialty societies. VALUES:
      The quality of evidence in this document was rated using the criteria described
      in Report of the Canadian Task Force on Preventive Health Care (Table 1).
      CONCLUSION: Individuals incubating EVD but who do not yet have symptoms are not
      infectious. The chance of a pregnant woman presenting with EVD in Canada is
      minimal, as are the chances of her infecting others if reasonable precautions are
      in place. EVIDENCE of maternal-fetal transmission is limited and anecdotal.

PMID- 25767951
TI  - New insights in the control of vascular permeability: vascular endothelial
      cadherin and other players.
AB  - PURPOSE OF REVIEW: The control of the endothelial barrier function is essential
      for vascular homeostasis and is mainly mediated by cell-to-cell junctions that
      tightly regulate permeability to plasma solutes and circulating cells such as
      leukocytes and tumor cells. While in some circumstances the transient dismantling
      of endothelial cell junctions might be beneficial, in pathological conditions,
      such as cancer, severe alterations of endothelial junction composition and
      function are detrimental, causing massive edema and increased interstitial
      pressure. Here, we aim to discuss the newly and most recently identified
      molecular mechanisms that cooperate in the control of vascular permeability.
      RECENT FINDINGS: Although the involvement of vascular endothelial-cadherin in the
      regulation of vascular leakage is well known, recent findings shed light on
      additional molecules involved in the control of vascular endothelial-cadherin
      phosphorylation in physiological and pathological conditions, and identified new
      unknown regulators of the endothelial barrier function. SUMMARY: In the past
      years, several studies explored the contribution of various signaling pathways in
      the regulation of vascular leakage. Despite encouraging results, a more
      comprehensive understanding of the molecular mechanisms involved in this process
      will define druggable targets for new therapeutic interventions to limit
      endothelial barrier dysfunctions.

PMID- 25767952
TI  - Erythropoiesis and transferrin receptors.
AB  - PURPOSE OF REVIEW: The type 1 transferrin receptor (TfR1) is well known as a key
      player in erythroid differentiation through its role in iron uptake. Recently, it
      has been demonstrated that TfR1 could also have signaling functions in erythroid
      cells. Moreover, the second transferrin receptor, TfR2, whose signaling functions
      in hepatic cells are well established, was recently shown to be a partner of the
      erythropoietin receptor (EpoR) and thereby likely to play a role in erythroid
      differentiation. RECENT FINDINGS: This review reports recent findings regarding
      the specificities of the regulation of TfR1 expression and iron uptake in
      erythroblasts. The newly discovered noncanonical actions of TfR1 and TfR2 in
      erythroid cells are also discussed. SUMMARY: Erythrocytes contain more than 60%
      of the iron of the body and each day, differentiating erythroid cells uptake
      around 20 mg of iron for heme synthesis. Accordingly, TfR1 is one of the most
      abundant membrane proteins of the erythroblasts and it is not surprising that
      specific regulations regarding both its expression and its mechanism of action
      operate in erythroblasts. The signaling functions of both TfR1 and TfR2 in
      erythroid cells were unexpected and these recent findings open a new field of
      research regarding the last steps of erythroid differentiation and their
      regulation.

PMID- 25767953
TI  - Endothelial cells and cancer cells: metabolic partners in crime?
AB  - PURPOSE OF REVIEW: Endothelial cells line the blood vessel lumen and are critical
      for blood flow homeostasis. Excessive and deregulated vessel overgrowth is a
      hallmark of pathological (tumor) angiogenesis. The purpose of this review is to
      describe the metabolic features of endothelial cells, in comparison with those of
      the cancer cells, and to discuss novel antiangiogenesis approaches based on
      targeting endothelial cell metabolism. RECENT FINDINGS: To form new blood
      vessels, endothelial cells switch from quiescence to a highly active state,
      characterized by migration and proliferation of endothelial cells. To date,
      growth factors, cytokines, and other molecules have been demonstrated to regulate
      vessel sprouting. However, recent evidence indicates that endothelial cell
      metabolism also importantly regulates angiogenesis. Whereas cancer cell
      metabolism has been studied extensively, endothelial cell metabolism is still in
      its infancy. SUMMARY: We will discuss metabolic pathways that regulate vessel
      sprouting, and highlight the commonalities with cancer cells for as much as
      studied. We will also consider new opportunities for the development of
      alternative antiangiogenic therapies by targeting endothelial cell metabolism.

PMID- 25767954
TI  - Posttranscriptional adaptations of the vascular endothelium to hypoxia.
AB  - PURPOSE OF REVIEW: Remarkable new advances have been made in the field of
      posttranscriptional gene regulation over recent years. These include the
      revelation of noncoding RNAs, such as microRNAs, antisense transcripts and their
      interactions with RNA-binding proteins (RBPs) in the context of both health and
      disease settings, such as hypoxia. In particular, these discoveries bear much
      relevance to the field of vascular biology, which historically has focused upon
      transcriptional processes. Thus, the contributions of these posttranscriptional
      gene regulatory mechanisms to vascular and endothelial biology represent a newer
      concept that warrants discussion. RECENT FINDINGS: Recent studies have revealed
      two emerging themes that are critical to endothelial/vascular biology and
      function. First is the functional integration between the microRNA pathway and
      the cellular hypoxic response, which, in addition to specific microRNAs, involves
      key components of the microRNA biogenesis machinery. A key concept here is the
      regulation of a master transcriptional programme through posttranscriptional
      mechanisms. The second major theme involves the dynamic interactions between
      RBPs, microRNAs and antisense RNAs. The condition-dependent collaborations and
      competitions between these different classes of posttranscriptional regulators
      reveal a critical layer of control for gene expression. SUMMARY: Taken together,
      these findings bear significant diagnostic and therapeutic implications for
      vascular disease.

PMID- 25767955
TI  - Differentiation of pluripotent stem cells into endothelial cells.
AB  - PURPOSE OF REVIEW: Methods to isolate endothelial cells from murine and human
      pluripotent stem cells continue to evolve and increasingly diverse endothelial
      cell populations have been generated. This review provides an update of key
      articles published within the past year that report on some of those advances.
      RECENT FINDINGS: Cooperative interactions among microRNA (miRNA), transcription
      factors and some downstream interacting proteins have been reported to enhance
      endothelial specification from embryonic stem cells (ESCs) and induced
      pluripotent stem cells (iPSCs). Endothelial cell differentiation can also be
      modulated by various growth factor additions, Notch pathway activation or
      inhibition, and modulation of the microenvironment of the differentiating ESC and
      iPSC. Functionality of the derived endothelium has been demonstrated by a variety
      of in-vitro and in-vivo assays. Finally, two recent reports have identified
      endothelial progenitor populations with robust proliferative potential. SUMMARY:
      Progress in differentiating endothelial cells from ESC and iPSC has been made.
      The recent report of formation of endothelial colony forming cells from human ESC
      and iPSC provides a protocol that can generate clinically relevant numbers of
      cells for human cell therapy.

PMID- 25767956
TI  - Host-parasite interactions that guide red blood cell invasion by malaria
      parasites.
AB  - PURPOSE OF REVIEW: Malaria is caused by the infection and proliferation of
      parasites from the genus Plasmodium in red blood cells (RBCs). A free Plasmodium
      parasite, or merozoite, released from an infected RBC must invade another RBC
      host cell to sustain a blood-stage infection. Here, we review recent advances on
      RBC invasion by Plasmodium merozoites, focusing on specific molecular
      interactions between host and parasite. RECENT FINDINGS: Recent work highlights
      the central role of host-parasite interactions at virtually every stage of RBC
      invasion by merozoites. Biophysical experiments have for the first time measured
      the strength of merozoite-RBC attachment during invasion. For P. falciparum,
      there have been many key insights regarding the invasion ligand PfRh5 in
      particular, including its influence on host species tropism, a co-crystal
      structure with its RBC receptor basigin, and its suitability as a vaccine target.
      For P. vivax, researchers identified the origin and emergence of the parasite
      from Africa, demonstrating a natural link to the Duffy-negative RBC variant in
      African populations. For the simian parasite P. knowlesi, zoonotic invasion into
      human cells is linked to RBC age, which has implications for parasitemia during
      an infection and thus malaria. SUMMARY: New studies of the molecular and cellular
      mechanisms governing RBC invasion by Plasmodium parasites have shed light on
      various aspects of parasite biology and host cell tropism, and indicate
      opportunities for malaria control.

PMID- 25767957
TI  - Update of hematopoietic cell transplantation for sickle cell disease.
AB  - PURPOSE OF REVIEW: Hematopoietic cell transplantation (HCT) is a curative therapy
      for sickle cell disease (SCD) that is utilized very rarely because of limited
      allogeneic donor availability, limited healthcare resources needed to expand the
      treatment to regions in the world where most affected individuals reside, and by
      a view among SCD experts that HCT lacks the evidential rigor with short and long
      term toxicity profiles that together might support its broader application.
      RECENT FINDINGS: In this update, recent advances focused on donor selection,
      reduced toxicity preparation for HCT, and treatment of young adults will be
      presented. The current status of conventional bone marrow transplantation with a
      human leukocyte antigen-identical sibling donor is summarized. SUMMARY: HCT for
      SCD is curative in almost all children who have a human leukocyte antigen-matched
      sibling donor. The future of this therapy will hinge on expanding the number of
      individuals who might be treated.

PMID- 25767958
TI  - New imaging methods and tools to study vascular biology.
AB  - PURPOSE OF REVIEW: Throughout history, development of novel microscopy techniques
      has been of fundamental importance to advance the vascular biology field.This
      review offers a concise summary of the most recently developed imaging techniques
      and discusses how they can be applied to vascular biology. In addition, we
      reflect upon the most important fluorescent reporters for vascular research that
      are currently available. RECENT FINDINGS: Recent advances in light sheet-based
      imaging techniques now offer the ability to live image the vascular system in
      whole organs or even in whole animals during development and in pathological
      conditions with a satisfactory spatial and temporal resolution. Conversely, super
      resolution microscopy now allows studying cellular processes at a near-molecular
      resolution. SUMMARY: Major recent improvements in a number of imaging techniques
      now allow study of vascular biology in ways that could not be considered
      previously. Researchers now have well-developed tools to specifically examine the
      dynamic nature of vascular development during angiogenic sprouting, remodeling
      and regression as well as the vascular responses in disease situations in vivo.
      In addition, open questions in endothelial and lymphatic cell biology that
      require subcellular resolution such as actin dynamics, junctional complex
      formation and stability, vascular permeability and receptor trafficking can now
      be approached with high resolution.

PMID- 25767959
TI  - Regioselectivity in ligand substitution reactions on diiron complexes governed by
      nucleophilic and electrophilic ligand properties.
AB  - The discovery of a diiron organometallic site in nature within the diiron
      hydrogenase, [FeFe]-H2ase, active site has prompted revisits of the classic
      organometallic chemistry involving the Fe-Fe bond and bridging ligands,
      particularly of the (MU-SCH2XCH2S)[Fe(CO)3]2 and (MU-SCH2XCH2S)[Fe(CO)2L]2 (X =
      CH2, NH; L = PMe3, CN(-), and NHC's (NHC = N-heterocyclic carbene)), derived from
      CO/L exchange reactions. Through the synergy of synthetic chemistry and density
      functional theory computations, the regioselectivity of nucleophilic (PMe3 or CN(
      )) and electrophilic (nitrosonium, NO(+)) ligand substitution on the diiron
      dithiolate framework of the (MU-pdt)[Fe(CO)2NHC][Fe(CO)3] complex (pdt =
      propanedithiolate) reveals the electron density shifts in the diiron core of such
      complexes that mimic the [FeFe]-H2ase active site. While CO substitution by PMe3,
      followed by reaction with NO(+), produces (MU-pdt)(MU
      CO)[Fe(NHC)(NO)][Fe(CO)2PMe3](+), the alternate order of reagent addition
      produces the structural isomer (MU-pdt)[Fe(NHC)(NO)PMe3][Fe(CO)3](+),
      illustrating how the nucleophile and electrophile choose the electron-poor metal
      and the electron-rich metal, respectively. Theoretical explorations of simpler
      analogues, (MU-pdt)[Fe(CO)2CN][Fe(CO)3](-), (MU-pdt)[Fe(CO)3]2, and (MU
      pdt)[Fe(CO)2NO][Fe(CO)3](+), provide an explanation for the role that the
      electron-rich iron moiety plays in inducing the rotation of the electron-poor
      iron moiety to produce a bridging CO ligand, a key factor in stabilizing the
      electron-rich iron moiety and for support of the rotated structure as found in
      the enzyme active site. 

PMID- 25767961
TI  - Informing policy to deliver comprehensive care for women veterans.

PMID- 25767962
TI  - A partnered research initiative to accelerate implementation of comprehensive
      care for women veterans: the VA women's health CREATE.

PMID- 25767964
TI  - Traumatic brain injury among women veterans: an invisible wound of intimate
      partner violence.
AB  - BACKGROUND: Intimate partner violence (IPV) is prevalent among women Veterans and
      is known to increase women's risk for traumatic brain injury (TBI). IPV-related
      TBI has not been examined in the women Veteran population. OBJECTIVES: To
      identify the occurrence of IPV-related TBI in a sample of women Veterans and
      examine the associations of IPV-related TBI with sociodemographic
      characteristics, health symptoms, health care utilization, and IPV experiences.
      RESEARCH DESIGN: Cross-sectional mail survey conducted in 2013. SUBJECTS: The
      sample comprised 176 New England Department of Veterans Affairs (VA) women
      Veteran patients. MEASURES: Self-reported IPV-related TBI was assessed with a
      modified VA TBI screening tool. The survey included validated measures of
      depression (Center for Epidemiologic Studies Depression Scale) and posttraumatic
      stress disorder (PTSD; Posttraumatic Disorder Checklist) symptoms, as well as
      overall mental and physical health (SF-12), and IPV (Conflict Tactics Scales
      Revised-2). Questions assessed past-year VA and non-VA health care use. RESULTS:
      A total of 18.8% (n=33) met screening criteria for IPV-related TBI history. Women
      who experienced IPV-related TBI reported significantly higher depression (mean
      Center for Epidemiologic Studies Depression Scale scores: 26.6 vs. 20.7,
      P<0.0001) and PTSD (mean Posttraumatic Disorder Checklist scores: 53.2 vs. 34.1,
      P<0.0001) symptoms, and poorer perceptions of physical health (mean SF-12 34.6
      vs. 42.3, P<0.01) than women who experienced IPV to the head without TBI. IPV
      related TBI was also associated with poorer perceptions of mental health, as well
      as more frequent VA health care utilization and overall IPV. CONCLUSIONS: IPV
      related TBI is associated with poorer mental and physical health in women
      Veterans. This invisible injury is associated with greater VA health care
      utilization and IPV exposure. Implications for VA practice and policy are
      discussed.

PMID- 25767963
TI  - Sex differences in mental health and substance use disorders and treatment entry
      among justice-involved Veterans in the Veterans Health Administration.
AB  - BACKGROUND: Over half of veterans in the criminal justice system have mental
      health or substance use disorders. However, there is a critical lack of
      information about female veterans in the criminal justice system and how
      diagnosis prevalence and treatment entry differ by sex. OBJECTIVES: To document
      prevalence of mental health and substance use disorder diagnoses and treatment
      entry rates among female veterans compared with male veterans in the justice
      system. RESEARCH DESIGN: Retrospective cohort study using national Veterans
      Health Administration clinical/administrative data from veterans seen by Veterans
      Justice Outreach Specialists in fiscal years 2010-2012. SUBJECTS: A total of 1535
      females and 30,478 male veterans were included. MEASURES: Demographic
      characteristics (eg, sex, age, residence, homeless status), mental health
      disorders (eg, depression, post-traumatic stress disorder), substance use
      disorders (eg, alcohol and opioid use disorders), and treatment entry (eg,
      outpatient, residential, pharmacotherapy). RESULTS: Among female veterans,
      prevalence of mental health and substance use disorders was 88% and 58%,
      respectively, compared with 76% and 72% among male veterans. Women had higher
      odds of being diagnosed with a mental health disorder [adjusted odds ratio
      (AOR)=1.98; 95% confidence interval (CI), 1.68-2.34] and lower odds of being
      diagnosed with a substance use disorder (AOR=0.50; 95% CI, 0.45-0.56) compared
      with men. Women had lower odds of entering mental health residential treatment
      (AOR=0.69; 95% CI, 0.57-0.83). CONCLUSIONS: Female veterans involved in the
      justice system have a high burden of mental health disorders (88%) and more than
      half have substance use disorders (58%). Entry to mental health residential
      treatment for women is an important quality improvement target.

PMID- 25767965
TI  - The effect of medical comorbidities on male and female Veterans' use of
      psychotherapy for PTSD.
AB  - BACKGROUND: Posttraumatic stress disorder (PTSD) is associated with an increased
      risk for medical comorbidities that may prevent participation in psychotherapy.
      The present study investigated whether medical comorbidities were associated with
      lower initiation rates and fewer psychotherapy visits for PTSD. Because women are
      more likely to initiate psychotherapy after traumatic events, we also assessed
      whether relationships were weaker among women. METHODS: Veterans (N=482, 47%
      women) recently diagnosed with PTSD completed a survey assessing demographics,
      mood, functional status, and interest in treatment. Data on medical
      comorbidities, psychotherapy visits, antidepressant prescriptions, and service
      connection were assessed longitudinally through administrative files. Logistic
      and negative binomial regressions assessed associations between number of medical
      comorbidities in the 2 years before the survey and the initiation and number of
      psychotherapy visits for PTSD in the year after the survey. All analyses were
      stratified by sex and controlled for survey and administrative variables.
      RESULTS: The relationship between medical comorbidities and number of
      psychotherapy visits was stronger among women than among men. A greater number of
      medical comorbidities was associated with significantly fewer psychotherapy
      visits in the total sample [incidence rate ratio: 0.91; 95% confidence interval
      (CI): 0.83, 1.00] and among women (incidence rate ratio: 0.87; 95% CI: 0.77,
      0.99), but not among men (95% CI: 0.75, 1.01). Medical comorbidities were not
      associated with the initiation of psychotherapy among men or women. CONCLUSIONS:
      Addressing medical comorbidities may help individuals remain in psychotherapy for
      PTSD. Medical comorbidities may play a larger role in the number of psychotherapy
      visits among women than men.

PMID- 25767966
TI  - Associations between race-based and sex-based discrimination, health, and
      functioning: a longitudinal study of Marines.
AB  - BACKGROUND: Only a few studies have examined race-based discrimination (RBD) and
      sex-based discrimination (SBD) in military samples and all are cross-sectional.
      OBJECTIVES: The current study examined associations between both RBD and SBD
      experienced during Marine recruit training and several health and functioning
      outcomes 11 years later in a racially/ethnically diverse sample of men and women.
      RESEARCH DESIGN: Linear multiple regression models were used to examine
      associations between sex, race/ethnicity, RBD and SBD, and later outcomes
      (physical health, self-esteem, and occupational/vocational functioning),
      accounting for baseline levels and covariates. SUBJECTS: Data were drawn from a
      larger longitudinal investigation of US Marine Corps recruits. The sample (N=471)
      was comprised of white men (34.6%), white women (37.6%), racial/ethnic minority
      men (12.7%), and racial/ethnic minority women (15.1%). MEASURES: Self-report
      measures of sex and race (T1), RBD and SBD (T2), social support (T2), mental
      health (T2), physical health (T2 and T5), self-esteem (T2 and T5), and
      occupational/vocational functioning (T5) were included. RESULTS: Over a decade
      later, experiences of RBD were negatively associated with physical health and
      self-esteem. Social support was the strongest predictor of
      occupational/vocational functioning. Effects of sex, SBD, and minority status
      were not significant in regressions after accounting for other variables.
      CONCLUSIONS: Health care providers can play a key role in tailoring care to the
      needs of these important subpopulations of veterans by assessing and
      acknowledging experiences of discrimination and remaining aware of the potential
      negative associations between discrimination and health and functioning above and
      beyond the contributions of sex and race/ethnicity.

PMID- 25767967
TI  - Post-sexual assault health care utilization among OEF/OIF servicewomen.
AB  - BACKGROUND AND OBJECTIVES: Few who experience sexual assault seek health care
      immediately. Yet many become heavy users of health care resources in the years
      postassault because sexual violence has been linked with both acute and chronic
      health consequences. Our objective was to investigate servicewomen's medical and
      mental health (MH) care utilization after sexual assault in-military (SAIM) and
      identify reasons for not seeking care. METHODS: In a retrospective cross
      sectional Midwestern community sample of OEF/OIF Active Component and
      Reserve/National Guard servicewomen, currently serving and veterans, computer
      assisted telephone interviews were conducted with 207 servicewomen who
      experienced SAIM. RESULTS: A quarter (25%) received post-SAIM MH care and 16%
      medical care. Utilization of medical care tended to be sooner (within the first
      month) and MH care later (6 mo to 1+ y). Most sought care on a military base, a
      third from civilian providers, and 10% sought MH from Veterans Health
      Administration. Servicewomen were more likely to have utilized medical care if
      they had experienced a completed SAIM and made a Department of Defense SAIM
      report and MH care if they were white, experienced on-duty SAIM, and made a
      Department of Defense SAIM report. The most common reason for not seeking medical
      care was due to belief that care was not needed. Reasons for not utilizing
      medical or MH care included embarrassment, confidentiality concerns, and fear of
      adverse career consequences. CONCLUSIONS: Few servicewomen utilized post-SAIM
      care, thus assault-specific health consequences were likely unaddressed. Given
      the severe and chronic consequences of sexual assault, our findings emphasize
      need for military, Veterans Health Administration, and civilian providers to
      query SAIM history to provide timely and optimal care.

PMID- 25767968
TI  - Chronic multisymptom illness among female Veterans deployed to Iraq and
      Afghanistan.
AB  - BACKGROUND: Chronic multisymptom illness (CMI) may be more prevalent among female
      Operation Enduring Freedom/Operation Iraqi Freedom/Operation New Dawn
      (OEF/OIF/OND) deployed Veterans due to deployment-related experiences.
      OBJECTIVES: To investigate CMI-related diagnoses among female OEF/OIF/OND
      Veterans. RESEARCH DESIGN: We estimated the prevalence of the International
      Classification of Disease-9th edition-Clinical Modification coded CMI-related
      diagnoses of chronic fatigue syndrome, fibromyalgia (FM), and irritable bowel
      syndrome (IBS) among female OEF/OIF/OND Veterans with Veterans Health
      Administration (VHA) visits, FY2002-2012 (n=78,435). We described the
      characteristics of female Veterans with and without CMI-related diagnoses and VHA
      settings of first CMI-related diagnoses. RESULTS: The prevalence of CMI-related
      diagnoses among female OEF/OIF/OND Veterans was 6397 (8.2%), over twice as high
      as the prevalence 95,424 (3.9%) among the totality of female Veterans currently
      accessing VHA (P<0.01). There were statistically significant differences in age,
      education, marital status, military component, service branch, and proportions of
      those with depression and/or post-traumatic stress disorder diagnoses across
      females with and without CMI-related diagnoses. Diagnoses were mainly from
      primary care, women's health, and physical medicine and rehabilitation clinics.
      CONCLUSIONS: CMI-related diagnoses were more prevalent among female OEF/OIF/OND
      Veterans compared with all female Veterans who currently access VHA. Future
      studies of the role of mental health diagnoses as confounders or mediators of the
      association of OEF/OIF/OND deployment and CMI are warranted. These and other
      factors associated with CMI may provide a basis for enhanced screening to
      facilitate recognition of these conditions. Further work should evaluate models
      of care and healthcare utilization related to CMI in female Veterans.

PMID- 25767969
TI  - Women with breast cancer in the Veterans Health Administration: demographics,
      breast cancer characteristics, and trends.
AB  - An increasing number of women are being cared for within the Veterans Health
      Administration (VA). However, the demographics and trends of women with breast
      cancer at the VA has not been documented. We describe the demographics and breast
      cancer characteristics of the 4445 women enrolled in the VA and reported to the
      Department of Veterans Affairs Central Cancer Registry diagnosed with breast
      cancer from 1995 to 2012. The cases of breast cancer per year increased over time
      to 365 in 2012. Black women represented only 16% of women diagnosed with breast
      cancer in the VA in 1995-1999 but increased to 25% by 2010-2012 (P<0.001). The
      median age at diagnosis in 1995-1999 was 58.4 and decreased to 56.8 by 2010-2012
      (P<0.02). The fraction of breast cancers that were node negative was 45% in 1995
      1999 and increased to 64% in 2010-2012; correspondingly, women presented at an
      earlier stage in more recent years (P<0.001). Urban women with breast cancer
      cared for within the VA are more likely to be younger (P=0.04) and nonwhite
      (P<0.001) compared with rural women, but the breast tumor characteristics appear
      similar. Oncology physicians at the VA must be prepared to care for breast cancer
      among women as the number of cases is growing. With only 365 women diagnosed with
      breast cancer at the VA as per year 2012 and nearly 150 treating VA facilities,
      the number of breast cancer patients seen by a particular physician could be
      quite low, and this fact suggests a need for an evaluation of the quality and
      outcomes of breast cancer care at the VA. 

PMID- 25767970
TI  - Travel time and attrition from VHA care among women veterans: how far is too far?
AB  - BACKGROUND: Travel time, an access barrier, may contribute to attrition of women
      veterans from Veterans Health Administration (VHA) care. OBJECTIVE: We examined
      whether travel time influences attrition: (a) among women veterans overall, (b)
      among new versus established patients, and (c) among rural versus urban patients.
      RESEARCH DESIGN: This retrospective cohort study used logistic regression to
      estimate the association between drive time and attrition, overall and for
      new/established and rural/urban patients. SUBJECTS: In total, 266,301 women
      veteran VHA outpatients in the Fiscal year 2009. MEASURES: An "attriter" did not
      return for VHA care during the second through third years after her first 2009
      visit (T0). Drive time (log minutes) was between the patient's residence and her
      regular source of VHA care. "New" patients had no VHA visits within 3 years
      before T0. Models included age, service-connected disability, health status, and
      utilization as covariates. RESULTS: Overall, longer drive times were associated
      with higher odds of attrition: drive time adjusted odds ratio=1.11 (99%
      confidence interval, 1.09-1.14). The relationship between drive time and
      attrition was stronger among new patients but was not modified by rurality.
      CONCLUSIONS: Attrition among women veterans is sensitive to longer drive time.
      Linking new patients to VHA services designed to reduce distance barriers
      (telemedicine, community-based clinics, mobile clinics) may reduce attrition
      among women new to VHA.

PMID- 25767971
TI  - Creating a roadmap for delivering gender-sensitive comprehensive care for women
      Veterans: results of a national expert panel.
AB  - BACKGROUND: Women Veterans are a significant minority of users of the VA
      healthcare system, limiting provider and staff experience meeting their needs in
      environments historically designed for men. The VA is nonetheless committed to
      ensuring that women Veterans have access to comprehensive care in environments
      sensitive to their needs. OBJECTIVES: We sought to determine what aspects of care
      need to be tailored to the needs of women Veterans in order for the VA to deliver
      gender-sensitive comprehensive care. RESEARCH DESIGN: Modified Delphi expert
      panel process. SUBJECTS: Eleven clinicians and social scientists with expertise
      in women's health, primary care, and mental health. MEASURES: Importance of
      tailoring over 100 discrete aspects of care derived from the Institute of
      Medicine's definition of comprehensive care and literature-based domains of sex
      sensitive care on a 5-point scale. RESULTS: Panelists rated over half of the
      aspects of care as very-to-extremely important (median score 4+) to tailor to the
      needs of women Veterans. The panel arrived at 14 priority recommendations that
      broadly encompassed the importance of (1) the design/delivery of services
      sensitive to trauma histories, (2) adapting to women's preferences and
      information needs, and (3) sex awareness and cultural transformation in every
      facet of VA operations. CONCLUSIONS: We used expert panel methods to arrive at
      consensus on top priority recommendations for improving delivery of sex-sensitive
      comprehensive care in VA settings. Accomplishment of their breadth will require
      national, regional, and local strategic action and multilevel stakeholder
      engagement, and will support VA's national efforts at improving customer service
      for all Veterans.

PMID- 25767972
TI  - Assessment of the healthcare needs and barriers to VA use experienced by women
      veterans: findings from the national survey of women Veterans.
AB  - BACKGROUND: Prior regional studies of women Veterans identified barriers to
      Veterans Affairs (VA) healthcare use. However, these studies do not reflect the
      demographic profile of women Veterans nationally, recent advances in VA women's
      healthcare, and the national context of expanded healthcare alternatives.
      OBJECTIVE: To characterize health, VA perceptions, barriers, healthcare delivery
      preferences, and reasons for VA or non-VA healthcare use in a national women
      Veteran sample. METHODS: Cross-sectional, population-based 2008-2009 National
      Survey of Women Veterans (n=3611). RESULTS: VA users had worse physical and
      mental health than non-VA-only users and healthcare nonusers. Older women
      Veterans had worse physical health, whereas younger groups had worse mental
      health. Healthcare use was highest for dual users, followed by VA-only users, but
      did not differ by age group. Healthcare nonusers were most likely to lack a
      regular source for healthcare. Perceptions of VA care quality and sex
      appropriateness were highest for VA-only, followed by dual, then non-VA-only
      users. VA perceptions were guided by personal experience for 90% of VA users,
      versus media or other secondhand sources for 70% of other groups. Non-VA-only
      users and healthcare nonusers had more knowledge gaps about VA and misperceptions
      about VA eligibility and services; non-VA-only users more likely encountered VA
      enrollment barriers. CONCLUSIONS: Many nonusers had healthcare needs that were
      not met. Positive VA perceptions by women with first-hand VA experience,
      contrasted with VA knowledge gaps by those without such exposure, suggests the
      need for more education about available VA healthcare services. VA planning
      should account for mental health needs and healthcare use by younger women
      Veterans.

PMID- 25767973
TI  - Military and mental health correlates of unemployment in a national sample of
      women veterans.
AB  - BACKGROUND: The unemployment rate is currently higher among women Veterans than
      among male Veterans and civilian women. Employment is a key social determinant of
      health, with unemployment being strongly associated with adverse health.
      OBJECTIVE: To identify military-related and health-related characteristics
      associated with unemployment in women Veterans. RESEARCH DESIGN AND SUBJECTS:
      Secondary analysis of workforce participants (n=1605) in the National Survey of
      Women Veterans telephone survey. MEASURES: Demographics, mental health
      conditions, health care utilization, and military experiences and effects.
      Unemployment was defined as being in the labor force but unemployed and looking
      for work. ANALYSIS: The chi analyses to identify characteristics of unemployed
      women Veterans; logistic regression to identify independent factors associated
      with unemployment. RESULTS: Ten percent of women Veterans were unemployed.
      Independent correlates of unemployment were screening positive for depression
      [odds ratio (OR)=4.7; 95% confidence interval [CI], 1.8-12.4], military service
      during wartime (OR=2.9; 95%, CI 1.1-7.3), and service in the regular military
      (vs. in the National Guards/Reserves only) (OR=6.8; 95% CI, 2.2-20.5). Two
      postactive duty perceptions related to not being respected and understood as a
      Veteran were each independently associated with unemployment. CONCLUSIONS:
      Whether depression underlies unemployment, is exacerbated by unemployment, or
      both, it is critical to identify and treat depression among women Veterans, and
      also to investigate women Veterans' experiences and identities in civilian life.
      Community-based employers may need education regarding women Veterans' unique
      histories and strengths. Women who served in the regular military and during
      wartime may benefit from job assistance before and after they leave the military.
      Gender-specific adaptation of employment services may be warranted.

PMID- 25767974
TI  - Readying the workforce: evaluation of VHA's comprehensive women's health primary
      care provider initiative.
AB  - BACKGROUND: Veterans Health Administration (VHA) primary care providers (PCPs)
      often see few women, making it challenging to maintain proficiency in women's
      health (WH). Therefore, VHA in 2010 established Designated WH Providers, who
      would maintain proficiency in comprehensive WH care and be preferentially
      assigned women patients. OBJECTIVE: To evaluate early implementation of this
      national policy. METHODS: At each VHA health care system (N=140), the Women
      Veterans Program Manager completed a Fiscal Year 2012 workforce capacity
      assessment (response rate, 100%), representing the first time the national
      Designated WH Provider workforce had been identified. Assessment data were linked
      to administrative data. RESULTS: Of all VHA PCPs, 23% were Designated WH
      Providers; 100% of health care systems and 83% of community clinics had at least
      1 Designated WH Provider. On average, women veterans comprised 19% (SD=27%) of
      the patients Designated WH Providers saw in primary care, versus 5% (SD=7%) for
      Other PCPs (P<0.001). For women veterans using primary care (N=313,033), new
      patients were less likely to see a Designated WH Provider than established women
      veteran patients (52% vs. 64%; P<0.001). CONCLUSIONS: VHA has achieved its goal
      of a Designated WH Provider in every health care system, and is approaching its
      goal of a Designated WH Provider at every hospital/community clinic. Designated
      WH Providers see more women than do Other PCPs. However, as the volume of women
      patients remains low for many providers, attention to alternative approaches to
      maintaining proficiency may prove necessary, and barriers to assigning new women
      patients to Designated WH Providers merit attention.

PMID- 25767976
TI  - The role of research in a time of rapid change: lessons from research on women
      veterans' health.

PMID- 25767975
TI  - Associations between provider designation and female-specific cancer screening in
      women Veterans.
AB  - BACKGROUND: In 2010, the Department of Veterans Affairs Healthcare System (VA)
      implemented policy to provide Comprehensive Primary Care (for acute, chronic, and
      female-specific care) from designated Women's Health providers (DWHPs) at all VA
      sites. However, since that time no comparisons of quality measures have been
      available to assess the level of care for women Veterans assigned to these
      providers. OBJECTIVES: To evaluate the associations between cervical and breast
      cancer screening rates among age-appropriate women Veterans and designation of
      primary-care provider (DWHP vs. non-DWHP). RESEARCH DESIGN: Cross-sectional
      analyses using the fiscal year 2012 data on VA women's health providers,
      administrative files, and patient-specific quality measures. SUBJECTS: The sample
      included 37,128 women Veterans aged 21 through 69 years. MEASURES: Variables
      included patient demographic and clinical factors (ie, age, race, ethnicity,
      mental health diagnoses, obesity, and site), and provider factors (ie, DWHP
      status, sex, and panel size). Screening measures were defined by age-appropriate
      subgroups using VA national guidelines. RESULTS: Female-specific cancer screening
      rates were higher among patients assigned to DWHPs (cervical cytology 94.4% vs.
      91.9%, P<0.0001; mammography 86.3% vs. 83.3%, P<0.0001). In multivariable models
      with adjustment for patient and provider characteristics, patients assigned to
      DWHPs had higher odds of cervical cancer screening (odds ratio, 1.26; 95%
      confidence interval, 1.07-1.47; P<0.0001) and breast cancer screening (odds
      ratio, 1.24; 95% CI, 1.10-1.39; P<0.0001). CONCLUSIONS: As the proportion of
      women Veterans increases, assignment to DWHPs may raise rate of female-specific
      cancer screening within VA. Separate evaluation of sex neutral measures is needed
      to determine whether other measures accrue benefits for patients with DWHPs.

PMID- 25767977
TI  - Prevalence and correlates of cigarette smoking among operation Iraqi freedom-era
      and operation enduring freedom-era women from the Active Component military and
      Reserve/National Guard.
AB  - BACKGROUND: Tobacco use adversely affects the health and readiness of military
      personnel. Although rates of cigarette smoking have historically been elevated
      among men serving in the military, less is known about tobacco use in
      servicewomen. OBJECTIVES: To examine the prevalence and correlates of tobacco use
      among women serving in the Active Component (AC) and Reserve/National Guard (RNG)
      as well as factors associated with starting to smoke during military service.
      METHODS: Cross-sectional surveys of 1320 women serving in the AC or RNG were used
      to examine cigarette use in servicewomen. Associations between self-reported
      tobacco use history, sociodemographics, military service, and psychosocial
      factors were investigated using logistic regression analyses. RESULTS: Thirty-six
      percent of servicewomen had a lifetime history of cigarette use, with 18%
      reporting current smoking. Thirty-one percent of lifetime smokers initiated
      smoking during military service. Factors associated with current smoking included
      pay grade, marital status, use of psychotropic medications, past-year alcohol
      use, and lifetime illicit drug or illegal prescription medication use. An
      enlisted pay grade, being white, and a history of deployment were all associated
      with starting to smoke during military service. CONCLUSIONS: Although progress
      has been made in reducing the gap in tobacco use between military and civilian
      populations, nearly 1 in 5 servicewomen in our sample smoked cigarettes. Further
      efforts are needed to address tobacco use in this population. In addition to
      providing resources to assist smokers with quitting, additional attention should
      be given to preventing smoking initiation, particularly among deployed female
      personnel.

PMID- 25767978
TI  - Reproductive health diagnoses of women veterans using department of Veterans
      Affairs health care.
AB  - BACKGROUND: Little is known regarding the reproductive health needs of women
      Veterans using Department of Veterans Affairs (VA) health care. OBJECTIVE: To
      describe the reproductive health diagnoses of women Veterans using VA health
      care, how these diagnoses differ across age groups, and variations in
      sociodemographic and clinical characteristics by presence of reproductive health
      diagnoses. RESEARCH DESIGN: This study is a cross-sectional analysis of VA
      administrative and clinical data. SUBJECTS: The study included women Veterans
      using VA health care in FY10. MEASURES: Reproductive health diagnoses were
      identified through presence of International Classification of Disease, 9th
      Revision (ICD-9) codes in VA clinical and administrative records. The prevalence
      of specific diagnosis categories were examined by age group (18-44, 45-64, >=65
      y) and the most frequent diagnoses for each age group were identified.
      Sociodemographic and clinical characteristics were compared by presence of at
      least 1 reproductive health diagnosis. RESULTS: The most frequent reproductive
      health diagnoses were menstrual disorders and endometriosis among those aged 18
      44 years (n=16,658, 13%), menopausal disorders among those aged 45-64 years
      (n=20,707, 15%), and osteoporosis among those aged >=65 years (n=8365, 22%).
      Compared with women without reproductive health diagnoses, those with such
      diagnoses were more likely to have concomitant mental health (46% vs. 37%,
      P<0.001) and medical conditions (75% vs. 63%, P<0.001). CONCLUSIONS: Women
      Veterans using VA health care have diverse reproductive health diagnoses. The
      high prevalence of comorbid medical and mental health conditions among women
      Veterans with reproductive health diagnoses highlights the importance of
      integrating reproductive health expertise into all areas of VA health care,
      including primary, mental health, and specialty care.

PMID- 25767979
TI  - Infertility care among OEF/OIF/OND women Veterans in the Department of Veterans
      Affairs.
AB  - BACKGROUND: An increasing number of young women Veterans seek reproductive health
      care through the VA, yet little is known regarding the provision of infertility
      care for this population. The VA provides a range of infertility services for
      Veterans including artificial insemination, but does not provide in vitro
      fertilization. This study will be the first to characterize infertility care
      among OEF/OIF/OND women Veterans using VA care. METHODS: We analyzed data from
      the OEF/OIF/OND roster file from the Defense Manpower Data Center (DMDC)
      Contingency Tracking System Deployment file of military discharges from October
      1, 2001-December 30, 2010, which includes 68,442 women Veterans between the ages
      of 18 and 45 who utilized VA health care after separating from military service.
      We examined the receipt of infertility diagnoses and care using ICD-9 and CPT
      codes. RESULTS: Less than 2% (n=1323) of OEF/OIF/OND women Veterans received an
      infertility diagnosis during the study period. Compared with women VA users
      without infertility diagnosis, those with infertility diagnosis were younger,
      obese, black, or Hispanic, have a service-connected disability rating, a positive
      screen for military sexual trauma, and a mental health diagnosis. Overall, 22% of
      women with an infertility diagnosis received an infertility assessment or
      treatment. Thirty-nine percent of women Veterans receiving infertility assessment
      or treatment received this care from non-VA providers. CONCLUSIONS: Overall, a
      small proportion of OEF/OIF/OND women Veterans received infertility diagnoses
      from the VA during the study period, and an even smaller proportion received
      infertility treatment. Nearly 40% of those who received infertility treatments
      received these treatments from non-VA providers, indicating that the VA may need
      to examine the training and resources needed to provide this care within the VA.
      Understanding women's use of VA infertility services is an important component of
      understanding VA's commitment to comprehensive medical care for women Veterans.

PMID- 25767980
TI  - Gynecologists in the VA: do they enhance availability of sex-specific services
      and policies in the emergency department?
AB  - OBJECTIVES: To examine the association between on-site gynecology and
      availability of sex-specific services and policies in Department of Veterans
      Affairs (VA) emergency departments (EDs). RESEARCH DESIGN: Cross-sectional
      analysis using data from a VA national inventory of emergency services for women
      and gynecologist staffing information from the VA Office of Productivity,
      Efficiency, and Staffing. SUBJECTS: ED directors from all VA medical centers
      (N=120). MEASURES: We used logistic regression to evaluate the association
      between on-site gynecologist full-time equivalents (FTEs, <0.5 and >=0.5), and
      availability of sex-specific ED services, such as consult and follow-up within VA
      by a gynecologist, emergency contraception, rho (D) immunoglobulin, pelvic
      ultrasound, and transfer policies for obstetric and gynecologic emergencies. All
      analyses were adjusted for number of ED encounters by women. RESULTS: Greater
      gynecologist FTE (>=0.5 vs. <0.5) was associated with increased odds of on-site
      availability of a gynecology consultation in the ED [odds ratio (OR)=10.9; 95%
      confidence interval (CI): 3.2, 36.6] and gynecologist follow-up within VA after
      an ED encounter (OR=2.5; 95% CI: 1.0, 6.2). A positive trend was seen in
      availability of rho (D) immunoglobulin (OR=1.4; 95% CI: 0.6, 3.5) and presence of
      transfer policies for obstetric (OR=1.7; 95% CI: 0.7, 4.5) and gynecologic
      emergencies (OR=1.6; 95% CI: 0.6, 4.2). Half of the facilities with <0.5 FTE did
      not have transfer policies in place or under development. CONCLUSIONS: On-site
      gynecologist FTE is associated with improved availability of sex-specific care in
      EDs. Development of transfer processes for obstetric and gynecologic emergencies
      in settings with limited on-site gynecology is needed.

PMID- 25767981
TI  - Care coordination for women veterans: bridging the gap between systems of care.

PMID- 25767982
TI  - Building capacity in VA to provide emergency gynecology services for women.
AB  - BACKGROUND: Visits to Veterans Administration (VA) emergency departments (EDs)
      are increasingly being made by women. A 2011 national inventory of VA emergency
      services for women revealed that many EDs have gaps in their resources and
      processes for gynecologic emergency care. OBJECTIVES: To guide VA in addressing
      these gaps, we sought to understand factors acting as facilitators and/or
      barriers to improving VA ED capacity for, and quality of, emergency gynecology
      care. RESEARCH DESIGN: Semistructured interviews with VA emergency and women's
      health key informants. SUBJECTS: ED directors/providers (n=14), ED nurse managers
      (n=13), and Women Veteran Program Managers (n=13) in 13 VA facilities. RESULTS:
      Leadership, staff, space, demand, funding, policies, and community were noted as
      important factors influencing VA EDs building capacity and improving emergency
      gynecologic care for women Veterans. These factors are intertwined and cross
      multiple organizational levels so that each ED's capacity is a reflection not
      only of its own factors, but also those of its local medical center and non-VA
      community context as well as VA regional and national trends and policies.
      CONCLUSIONS: Policies and quality improvement initiatives aimed at building VA's
      emergency gynecologic services for women need to be multifactorial and aimed at
      multiple organizational levels. Policies need to be flexible to account for wide
      variations across EDs and their medical center and community contexts. Approaches
      that build and encourage local leadership engagement, such as evidence-based
      quality improvement methodology, are likely to be most effective.

PMID- 25767983
TI  - Early lessons learned in implementing a women's health educational and virtual
      consultation program in VA.
AB  - BACKGROUND: Many Veterans Health Administration primary care providers (PCPs)
      have small female patient caseloads, making it challenging for them to build and
      maintain their women's health (WH) knowledge and skills. To address this issue,
      we implemented a longitudinal WH-focused educational and virtual consultation
      program using televideo conferencing. OBJECTIVE: To perform a formative
      evaluation of the program's development and implementation. RESEARCH DESIGN: We
      used mixed methods including participant surveys, semi-structured interviews,
      stakeholder meeting field notes, and participation logs. We conducted qualitative
      content analysis for interviews and field notes, and quantitative tabulation for
      surveys and logs. SUBJECTS: Veterans Health Administration WH PCPs. RESULTS: In
      53 postsession surveys received, 47(89%) agreed with the statement, "The
      information provided in the session would influence my patient care." Among 18
      interviewees, all reported finding the program useful for building and
      maintaining WH knowledge. All interviewees also reported that sessions being
      conducted during their lunch hour limited consistent participation. Logs showed
      that PCPs participated more consistently in the 1 health care system that
      provided time specifically allocated for this program. Key stakeholder
      discussions revealed that rotating specialists and topics across the breadth of
      WH limited submission of cases. CONCLUSIONS: Our WH education and virtual
      consultation program is a promising modality for building and maintaining PCP
      knowledge of WH, and influencing patient care. However, allocated time for PCPs
      to participate is essential for robust and consistent participation. Narrowing
      the modality's focus to gynecology, rather than covering the breadth WH topics,
      may facilitate PCPs having active cased-based questions for sessions.

PMID- 25767984
TI  - Gender-specific mental health care needs of women veterans treated for
      psychiatric disorders in a Veterans Administration Women's Health Clinic.
AB  - OBJECTIVE: This pilot study aims to ascertain the prevalence of self-reported
      premenstrual, perinatal, and perimenopausal influences on mental health, and of
      gynecologic conditions that could interact with psychiatric conditions, among
      women veterans receiving psychiatric care within a Veterans Administration (VA)
      Women's Health Clinic (WHC). METHODS: Participants included all women veterans
      (N=68) who received psychiatric evaluations within a VA WHC over a 5-month
      period. This setting encompasses colocated and coordinated primary care,
      gynecologic and mental health services. Evaluations included a Women's Mental
      Health Questionnaire, a psychiatric interview, and medical record review.
      Deidentified data were extracted from a clinical data repository for this
      descriptive study. RESULTS: High proportions of study participants reported that
      their emotional problems intensified premenstrually (42.6%), during pregnancy
      (33.3%), in the postpartum period (33.3%), or during perimenopause (18.2%).
      Unintended pregnancy (70.0% of pregnancies) and pregnancy loss (63.5% of women
      who had been pregnant) were prominent sex-linked stressors. Dyspareunia (22.1% of
      participants) and pelvic pain (17.6% of participants) were frequent
      comorbidities. CONCLUSIONS: Among women veterans receiving psychiatric care
      within a VA WHC, there are high rates of self-reported premenstrual, perinatal,
      and perimenopausal influences on mental health. This population also has
      substantial comorbidity of psychiatric disorders with dyspareunia and pelvic
      pain. This underscores the importance of recognizing and addressing women
      veterans' sex-specific care needs, including interactions among reproductive
      cycle phases, gynecologic pain, and psychiatric symptoms. The findings support
      the need for greater awareness of the sex-specific mental health needs of women
      veterans, and for more definitive studies to further characterize these needs.

PMID- 25767985
TI  - Access to mental health care among women Veterans: is VA meeting women's needs?
AB  - BACKGROUND: Patient-centered access to mental health describes the fit between
      patient needs and resources of the system. To date, little data are available to
      guide implementation of services to women veterans, an underrepresented minority
      within Department of Veteran Affairs (VA) health care. The current study examines
      access to mental health care among women veterans, and identifies gender-related
      indicators of perceived access to mental health care. METHODS: A population-based
      sample of 6287 women veterans using VA primary care services participated in a
      survey of past year perceived need for mental health care, mental health
      utilization, and gender-related mental health care experiences. Subjective rating
      of how well mental health care met their needs was used as an indicator of
      perceived access. RESULTS: Half of all women reported perceived mental health
      need; 84.3% of those women received care. Nearly all mental health users (90.9%)
      used VA services, although only about half (48.8%) reported that their mental
      health care met their needs completely or very well. Gender related experiences
      (availability of female providers, women-only treatment settings, women-only
      treatment groups, and gender-related comfort) were each associated with 2-fold
      increased odds of perceived access, and associations remained after adjusting for
      ease of getting care. CONCLUSIONS: Women VA users demonstrate very good objective
      access to mental health services. Desire for, and access to specialized mental
      health services for women varies across the population and are important aspects
      of shared decision making in referral and treatment planning for women using VA
      primary care.

PMID- 25767986
TI  - Plant compounds enhance the assay sensitivity for detection of active Bacillus
      cereus toxin.
AB  - Bacillus cereus is an important food pathogen, producing emetic and diarrheal
      syndromes, the latter mediated by enterotoxins. The ability to sensitively trace
      and identify this active toxin is important for food safety. This study evaluated
      a nonradioactive, sensitive, in vitro cell-based assay, based on B. cereus toxin
      inhibition of green fluorescent protein (GFP) synthesis in transduced monkey
      kidney Vero cells, combined with plant extracts or plant compounds that reduce
      viable count of B. cereus in food. The assay exhibited a dose dependent GFP
      inhibition response with ~25% inhibition at 50 ng/mL toxin evaluated in culture
      media or soy milk, rice milk or infant formula, products associated with food
      poisonings outbreak. The plant extracts of green tea or bitter almond and the
      plant compounds epicatechin or carvacrol were found to amplify the assay response
      to ~90% inhibition at the 50 ng/mL toxin concentration greatly increasing the
      sensitivity of this assay. Additional studies showed that the test formulations
      also inhibited the growth of the B. cereus bacteria, likely through cell membrane
      disruption. The results suggest that the improved highly sensitive assay for the
      toxin and the rapid inactivation of the pathogen producing the toxin have the
      potential to enhance food safety. 

PMID- 25767987
TI  - Case-control Studies on the Effectiveness of Breast Cancer Screening: Insights
      from the UK Age Trial.
AB  - BACKGROUND: Ongoing breast cancer screening programs can only be evaluated using
      observational study designs. Most studies have observed a reduction in breast
      cancer mortality, but design differences appear to have resulted in different
      estimates. Direct comparison of case-control and trial analyses gives more
      insight into this variation. Here, we performed case-control analyses within the
      randomized UK Age Trial. METHODS: The Age Trial assessed the effect of screening
      on breast cancer mortality in women ages 40-49 years. In our approach, case
      subjects were defined as breast cancer deaths between trial entry (1991-1997) and
      2004. Women were ages 39-41 years at entry. For every case subject, five control
      subjects were selected. All case subjects were included in analyses of screening
      invitation (356 case subjects, 1,780 controls), whereas analyses of attendance
      were restricted to women invited to screening (105 case subjects, 525 age-matched
      controls). Odds ratios (OR) were estimated with conditional logistic regression.
      We used and compared two methods to correct for self-selection bias. RESULTS:
      Screening invitation resulted in a breast cancer mortality reduction of 17% (95%
      confidence interval [CI]: -36%, +6%), similar to trial results. Different
      exposure definitions and self-selection adjustments influenced the observed
      breast cancer mortality reduction. Depending on the method, "ever screened"
      appeared to be associated with a small reduction (OR: 0.86, 95% CI: 0.40, 1.89)
      or no reduction (OR: 1.02, 95% CI: 0.48, 2.14) using the two methods of
      correction. Recent attendance resulted in an adjusted mortality reduction of 36%
      (95% CI: -69%, +31%) or 45% (95% CI: -71%, +5%). CONCLUSIONS: Observational
      studies, and particularly case-control studies, are an important monitoring tool
      for breast cancer screening programs. The focus should be on diminishing bias in
      observational studies and gaining a better understanding of the influence of
      study design on estimates of mortality reduction.

PMID- 25767988
TI  - Elevated risk of nicotine dependence among sib-pairs discordant for maternal
      smoking during pregnancy: evidence from a 40-year longitudinal study.
AB  - BACKGROUND: Compelling evidence links maternal smoking during pregnancy with
      elevated risk of nicotine dependence among the offspring. However, no study to
      date has examined the maternal smoking during pregnancy-nicotine dependence link
      among sibling-pairs discordant for maternal smoking during pregnancy. We tested
      two hypotheses that, if supported, suggest that the maternal smoking during
      pregnancy-nicotine dependence link may be physiologically mediated. METHODS:
      Study participants were adult offspring of women enrolled in the Providence and
      Boston sites of the Collaborative Perinatal Project (1959-1966). Approximately
      10% of these adult offspring (average age: 39.6 years) were enrolled in the New
      England Family Study (n = 1,783), a follow-up study that oversampled families
      with multiple siblings. Logistic regression models predicting maternal smoking
      during pregnancy risk on various prospectively collected smoking and marijuana
      use outcomes, including nicotine dependence, were fit using models that allowed
      between-mother effects of maternal smoking during pregnancy exposure to differ
      from within-mother effects. In the absence of significant effect heterogeneity,
      we calculated a combined estimate. RESULTS: Maternal smoking during pregnancy
      predicted progression from weekly smoking to nicotine dependence (odds ratio =
      1.4 [95% confidence interval = 1.2, 1.8]), but not weekly smoking or progression
      to marijuana dependence. CONCLUSIONS: Current evidence from sibling-pairs
      discordant for maternal smoking during pregnancy is consistent with previous
      reports of a dose-response association between maternal smoking during pregnancy
      and nicotine dependence, as well as of up-regulation of nicotine receptors among
      animals exposed to maternal smoking during pregnancy. Together, they provide
      support for the existence of a physiologically mediated link between maternal
      smoking during pregnancy and nicotine dependence.

PMID- 25767989
TI  - Shape tailored green synthesis of CeO2:Ho3+ nanopowders, its structural,
      photoluminescence and gamma radiation sensing properties.
AB  - CeO2:Ho(3+) (1-9 mol%) nanopowders have been prepared by efficient and
      environmental friendly green combustion method using Aloe vera gel as fuel for
      the first time. The final products are well characterized by powder X-ray
      diffraction (PXRD), scanning electron microscopy (SEM), fourier transform
      infrared (FTIR). Bell, urchin, core shell and flower like morphologies are
      observed with different concentrations of the A. vera gel. It is apparent that by
      adjusting the concentration of the gel, considerable changes in the formation of
      CeO2:Ho(3+) nano structures can be achieved. Photoluminescence (PL) studies show
      green (543, 548 nm) and red (645, 732 nm) emissions upon excited at 400 nm
      wavelength. The emission peaks at ~526, 548, 655 and 732 nm are associated with
      the transitions of (5)F3->(5)I8, (5)S2->(5)I8, (5)F5->(5)I8 and (5)S2->(5)I7,
      respectively. Three TL glow peaks are observed at 118, 267 and 204 degrees C for
      all the gamma irradiated samples which specify the surface and deeper traps.
      Linear TL response in the range 0.1-2kGy shows that phosphor is fairly useful as
      gamma radiation dosimeter. Kinetic parameters associated with the glow peaks are
      estimated using Chen's half width method. The CIE coordinate values show that
      phosphor is quite useful for the possible applications in WLEDs as orange red
      phosphor.

PMID- 25767990
TI  - Coordination behavior of new bis Schiff base ligand derived from 2-furan
      carboxaldehyde and propane-1,3-diamine. Spectroscopic, thermal, anticancer and
      antibacterial activity studies.
AB  - Novel bis Schiff base ligand, [N1,N3-bis(furan-2-ylmethylene)propane-1,3
      diamine], was prepared by the condensation of furan-2-carboxaldehyde with propane
      1,3-diamine. Its conformational changes on complexation with transition metal
      ions [Co(II), Ni(II), Cu(II), Mn(II), Cd(II), Zn(II) and Fe(III)] have been
      studied on the basis of elemental analysis, conductivity measurements, spectral
      (infrared, (1)H NMR, electronic), magnetic and thermogravimetric studies. The
      conductance data of the complexes revealed their electrolytic nature suggesting
      them as 1:2 (for bivalent metal ions) and 1:3 (for Fe(III) ion) electrolytes. The
      complexes were found to have octahedral geometry based on magnetic moment and
      solid reflectance measurements. Thermal analysis data revealed the decomposition
      of the complexes in successive steps with the removal of anions, coordinated
      water and bis Schiff base ligand. The thermodynamic parameters were calculated
      using Coats-Redfern equation. The Anticancer screening studies were performed on
      human colorectal cancer (HCT), hepatic cancer (HepG2) and breast cancer (MCF-7)
      cell lines. The antimicrobial activity of all the compounds was studied against
      Gram negative (Escherichia coli and Proteus vulgaris) and Gram positive (Bacillus
      vulgaris and Staphylococcus pyogones) bacteria. It was observed that the
      coordination of metal ion has a pronounced effect on the microbial activities of
      the bis Schiff base ligand. All the metal complexes have shown higher
      antimicrobial effect than the free bis Schiff base ligand. 

PMID- 25767991
TI  - A highly sensitive fluorescence probe for metallothioneins based on tiron-copper
      complex.
AB  - The fabrication of tiron-copper complex as a novel fluorescence probe for the
      sensitive directly detection of metallothioneins at nanomolar levels was
      demonstrated. In Britton-Robinson (B-R) buffer (pH 7.50), the interaction of
      bis(tiron)copper(II) complex cation [Cu(tiron)2](2+) and metallothioneins
      enhanced the fluorescence intensity of the system. The fluorescence enhancement
      at 347 nm was proportional to the concentration of metallothioneins. The
      mechanism was studied and discussed in terms of the fluorescence spectra. Under
      the optimal experimental conditions, at 347 nm, there was a linear relationship
      between the fluorescence intensity and the concentration of the metallothioneins
      in the range of 8.80 * 10(-9)-7.70 * 10(-7)mol L(-1), with a correlation
      coefficient of r=0.995 and detection limit 2.60 * 10(-9)mol L(-1). The relative
      standard deviation was 0.77% (n=11), and the average recovery 94.4%. The method
      proposed was successfully reliable, selective and sensitive in determining of
      trace metallothioneins in fish visceral organ samples with the results in good
      agreement with those obtained by HPLC.

PMID- 25767992
TI  - 3-Iodobenzaldehyde: XRD, FT-IR, Raman and DFT studies.
AB  - The structure of 3-iodobenzaldehyde (3IB) was 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 3IB were examined using density functional theory
      (DFT) method, with the Becke-3-Lee-Yang-Parr (B3LYP) functional and the 6
      311+G(3df,p) basis set for all atoms except for iodine. The LANL2DZ effective
      core basis set was used for iodine. Potential energy distribution (PED) analysis
      of normal modes was performed to identify characteristic frequencies. 3IB
      crystallizes in monoclinic space group P21/c with the O-trans form. There is a
      good agreement between the theoretically predicted structural parameters, and
      vibrational frequencies and those obtained experimentally. In order to understand
      halogen effect, 3-halogenobenzaldehyde [XC6H4CHO; X=F, Cl and Br] was also
      studied theoretically. The free energy difference between the isomers is small
      but the rotational barrier is about 8kcal/mol. An atypical behavior of fluorine
      affecting conformational preference is observed. 

PMID- 25767995
TI  - Highlights in advanced prostate cancer from the 2014 AUA and ASCO meetings.

PMID- 25767993
TI  - Synthesis, spectral characterization, thermal behaviour, antibacterial activity
      and DFT calculation on N'-[bis(methylsulfanyl) methylene]-2-hydroxybenzohydrazide
      and N'-(4-methoxy benzoyl)-hydrazinecarbodithioic acid ethyl ester.
AB  - Two new compounds N'-[bis(methylsulfanyl) methylene]-2-hydroxybenzohydrazide
      {Hbmshb (1)} and N'-(4-methoxy benzoyl)-hydrazinecarbodithioic acid ethyl ester
      {H2mbhce (2)} have been synthesized and characterized with the aid of elemental
      analyses, IR, NMR and single crystal X-ray diffraction data. Compounds 1 and 2
      crystallize in orthorhombic and monoclinic systems with space group Pna21 and
      P21/n, respectively. Inter and intra molecular hydrogen bonding link two
      molecules and provide linear chain structure. In addition to this, compound 2 is
      stabilized by CH?pi and NH?pi interactions. Molecular geometry from X-ray
      analysis, geometry optimization, charge distribution, bond analysis, frontier
      molecular orbital (FMO) analysis and non-linear optical (NLO) effects have been
      performed using the density functional theory (DFT) with the B3LYP functional.
      The bioefficacy of compounds has been examined against the growth of bacteria to
      evaluate their anti-microbial potential. Compounds 1 and 2 are thermally stable
      and show NLO behaviour better than the urea crystal.

PMID- 25767996
TI  - Synthesis and properties of 6'-fluoro-tricyclo-DNA.
AB  - The synthesis of the two fluorinated tricyclic nucleosides 6'-F-tc-T and 6'-F-tc
      5(Me)C, as well as the corresponding building blocks for oligonucleotide
      assembly, was accomplished. An X-ray analysis of N(4)-benzoylated 6'-F-tc-(5Me)C
      reavealed a 2'-exo (north) conformation of the furanose ring, characterizing it
      as an RNA mimic. In contrast to observations in the bicyclo-DNA series, no short
      contact between the fluorine atom and the H6 of the base, reminiscent of a
      nonclassical F...H hydrogen bond, could be observed. Tm measurements of modified
      oligodeoxynucleotides with complementary RNA showed slightly sequence-dependent
      duplex stabilization profiles with maximum DeltaTm/mod values of +4.5  degrees C
      for 6'-F-tc-(5Me)C and +1  degrees C for 6'-F-tc-T. In comparison with parent tc
      modified oligonucleotides, no relevant changes in Tm were detected, attributing
      the fluorine substituent a neutral role in RNA affinity. A structural analysis of
      duplexes with DNA and RNA by CD-spectroscopy revealed a shift from B- to A-type
      conformation induced by the 6'-F-tc-nucleosides. This is not a specific "fluorine
      effect", as the same is also observed for the parent tc-modifications. The two
      fluorinated tc-nucleosides were also incorporated into a pure tricyclo-DNA
      backbone and showed no discrimination in Tm with complementary RNA, demonstrating
      that 6'-F substitution is also compatible within fully modified tc
      oligonucleotides. 

PMID- 25767997
TI  - Specimen extraction from the defunctioning ileostomy site or Pfannenstiel
      incision during total laparoscopic low anterior resection for rectal cancer.
AB  - INTRODUCTION: Laparoscopic low anterior resection is commonly performed, but
      there is controversy about the optimal specimen extraction site. The purpose of
      the study was to evaluate the outcomes of two different specimen extraction
      sites. MATERIALS AND METHODS: In this prospective study of total laparoscopic low
      anterior resection for rectal cancer, we compared the outcomes of specimen
      extraction from a right lower quadrant trocar site that is also used for a
      defunctioning ileostomy (21 patients) or a Pfannenstiel incision (25 patients).
      RESULTS: The median visual analog pain score on postoperative Days 1 and 3 and
      meperidine requirement were significantly higher in the Pfannenstiel than in the
      ileostomy site group. Time to resumption of oral diet and hospital stay were
      significantly shorter in the ileostomy site than in the Pfannenstiel group. All
      four parastomal hernias were observed in the ileostomy site group. CONCLUSIONS:
      Use of the stoma site for specimen extraction in total laparoscopic low anterior
      resection for rectal cancer may minimize abdominal wall incisions, decrease
      postoperative recovery time, decrease pain level and analgesic requirement, and
      improve cosmesis. Although this procedure may increase the incidence of
      parastomal hernia, hernia repair may be performed during ileostomy takedown
      surgery, and the temporary stoma site (which also is the right lower quadrant
      trocar entry site) may be suggested as a proper specimen extraction site.

PMID- 25767998
TI  - Speech recognition across the lifespan: Longitudinal changes from middle age to
      older adults.
AB  - Purpose: To provide an overview of evidence of age-related declines in speech
      recognition in middle-age to older adults, review contributions of pure-tone
      thresholds, age, and gender, and report preliminary results from a longitudinal
      study. Methods: Pure-tone thresholds and word recognition in quiet and babble are
      being measured in a large sample of adults yearly or every 2-3 years. Analyses
      included >1,200 adults whose ages ranged from 40s to 90s, with >16,000 audiograms
      and speech recognition scores. A multivariable generalized linear repeated mixed
      model assessed changes in thresholds and speech recognition over time. Results:
      Word recognition in quiet declined significantly while controlling for threshold
      increases, and declines appeared to accelerate near age 65-70. Scores for males
      were poorer than for females even after controlling for gender differences in
      thresholds, but rates of decline did not differ by gender. Smaller declines in
      key word recognition in babble were observed and declines appeared to accelerate
      near age 75-80. Conclusions: Additional evidence is needed from large-scale
      longitudinal cohort studies to determine rates of change of auditory function
      across the lifespan. These studies can identify associations with modifiable risk
      factors and potential mechanisms to reduce, prevent, or delay the onset of age
      related hearing loss.

PMID- 25767999
TI  - Plasmonics on the slope of enlightenment: the role of transition metal nitrides.
AB  - The key problem currently faced by plasmonics is related to material limitations.
      After almost two decades of extreme excitement and research largely based on the
      use of noble metals, scientists have come to a consensus on the importance of
      exploring alternative plasmonic materials to address application-specific
      challenges to enable the development of new functional devices. Such a change in
      motivation will undoubtedly lead to significant advancements in plasmonics
      technology transfer and could have a revolutionary impact on nanophotonic
      technologies in general. Here, we report on one of the approaches that, together
      with other new material platforms, mark an insightful technology-driven era for
      plasmonics. Our study focuses on transition metal nitrides as refractory
      plasmonic materials that exhibit appealing optical properties in the visible and
      near infrared regions, along with high temperature durability. We take heat
      assisted magnetic recording as a case study for plasmonic technology and show
      that a titanium nitride antenna satisfies the requirements for an optically
      efficient, durable near field transducer paving the way to the next-generation
      data recording systems. 

PMID- 25768000
TI  - Regenerating gene 1B silencing inhibits colon cancer cell HCT116 proliferation
      and invasion.
AB  - BACKGROUND: The human regenerating gene 1B (REG1B) is found to be frequently up
      regulated in many types of human tumors. It is unclear whether REG1B expression
      may have therapeutic value in colorectal carcinoma. Additionally, how REG1B is
      associated with the clinical features of colorectal carcinoma is not known. To
      investigate the relationship between REG1B and colorectal cancer, we analyzed
      REG1B expression in clinical specimens and cell lines and the effect of down
      regulation of REG1B by short hairpin RNA (shRNA) in HCT116 cells. METHODS:
      Paraffin-embedded specimens from 30 pairs of colorectal cancer tissues and
      adjacent colon tissues were used to investigate the expression of REG1B by
      immunohistochemistry. We also examined whether REG1B itself may be related to
      cell proliferation, cell cycle arrest, apoptosis, migration and invasion in colon
      cancer HCT116 cells. RESULTS: Our results showed that REG1B was highly expressed
      in colorectal carcinoma and was significantly associated with cell
      differentiation status. The results also illustrated that REG1B silencing with
      shRNA inhibited cell proliferation, migration and invasion but did not induce
      apoptosis. Furthermore, down-regulation of REG1B induces G1-phase cell cycle
      arrest in colon cancer cells. CONCLUSIONS: Knockdown of REG1B can inhibit cell
      proliferation, migration and invasion. It may act by a mechanism regulating cell
      cycle progression. Thus, REG1B may be a novel candidate therapeutic target for
      colorectal cancer.

PMID- 25768002
TI  - Electrical delay line multiplexing for pulsed mode radiation detectors.
AB  - Medical imaging systems are composed of a large number of position sensitive
      radiation detectors to provide high resolution imaging. For example, whole-body
      Positron Emission Tomography (PET) systems are typically composed of thousands of
      scintillation crystal elements, which are coupled to photosensors. Thus, PET
      systems greatly benefit from methods to reduce the number of data acquisition
      channels, in order to reduce the system development cost and complexity. In this
      paper we present an electrical delay line multiplexing scheme that can
      significantly reduce the number of readout channels, while preserving the signal
      integrity required for good time resolution performance. We experimented with two
      4 * 4 LYSO crystal arrays, with crystal elements having 3 mm * 3 mm * 5 mm and 3
      mm * 3 mm * 20 mm dimensions, coupled to 16 Hamamatsu MPPC S10931-050P SiPM
      elements. Results show that each crystal could be accurately identified, even in
      the presence of scintillation light sharing and inter-crystal Compton scatter
      among neighboring crystal elements. The multiplexing configuration degraded the
      coincidence timing resolution from ~243 ps FWHM to ~272 ps FWHM when 16 SiPM
      signals were combined into a single channel for the 4 * 4 LYSO crystal array with
      3 mm * 3 mm * 20 mm crystal element dimensions, in coincidence with a 3 mm * 3 mm
      * 5 mm LYSO crystal pixel. The method is flexible to allow multiplexing
      configurations across different block detectors, and is scalable to an entire
      ring of detectors. 

PMID- 25768001
TI  - The Genetic Architecture of Arsenic Metabolism Efficiency:A SNP-Based
      Heritability Study of Bangladeshi Adults.
AB  - BACKGROUND: Consumption of arsenic-contaminated drinking water adversely affects
      health. There is interindividual variation in arsenic metabolism efficiency,
      partially due to genetic variation in the arsenic methyltransferase (AS3MT) gene
      region. OBJECTIVES: The goal of this study was to assess the overall contribution
      of genetic factors to variation in arsenic metabolism efficiency, as measured by
      the relative concentration of dimethylarsinic acid (DMA%) in urine. METHODS:
      Using data on genome-wide single nucleotide polymorphisms (SNPs) and urinary DMA%
      for 2,053 arsenic-exposed Bangladeshi individuals, we employed various SNP-based
      approaches for heritability estimation and polygenic modeling. RESULTS: Using
      data on all participants, the percent variance explained (PVE) for DMA% by all
      measured and imputed SNPs was 16% (p = 0.08), which was reduced to 5% (p = 0.34)
      after adjusting for AS3MT SNPs. Using information on close relatives only, the
      PVE was 63% (p = 0.0002), but decreased to 41% (p = 0.01) after adjusting for
      AS3MT SNPs. Regional heritability analysis confirmed 10q24.32 (AS3MT) as a major
      arsenic metabolism locus (PVE = 7%, p = 4.4 * 10(-10)), but revealed no
      additional regions. We observed a moderate association between a polygenic score
      reflecting elevated DMA% (composed of thousands of non-AS3MT SNPs) and reduced
      skin lesion risk in an independent sample (p < 0.05). We observed no associations
      for SNPs reported in prior candidate gene studies of arsenic metabolism.
      CONCLUSIONS: Our results suggest that there are common variants outside of the
      AS3MT region that influence arsenic metabolism in Bangladeshi individuals, but
      the effects of these variants are very weak compared with variants near AS3MT.
      The high heritability estimates observed using family-based heritability
      approaches suggest substantial effects for rare variants and/or unmeasured
      environmental factors.

PMID- 25768003
TI  - Towards the systematic mapping and engineering of the protein prenylation
      machinery in Saccharomyces cerevisiae.
AB  - Protein prenylation is a widespread and highly conserved eukaryotic post
      translational modification that endows proteins with the ability to reversibly
      attach to intracellular membranes. The dynamic interaction of prenylated proteins
      with intracellular membranes is essential for their signalling functions and is
      frequently deregulated in disease processes such as cancer. As a result, protein
      prenylation has been pharmacologically targeted by numerous drug discovery
      programs, albeit with limited success. To a large extent, this can be attributed
      to an insufficient understanding of the interplay of different protein
      prenyltransferases and the combinatorial diversity of the prenylatable sequence
      space. Here, we report a high-throughput, growth-based genetic selection assay in
      Saccharomyces cerevisiae based on the Ras Recruitment System which, for the first
      time, has allowed us to create a comprehensive map of prenylatable protein
      sequences in S. cerevisiae. We demonstrate that potential prenylatable space is
      sparsely (6.2%) occupied leaving room for creation of synthetic orthogonal
      prenylatable sequences. To experimentally demonstrate that, we used the developed
      platform to engineer mutant farnesyltransferases that efficiently prenylate
      substrate motives that are not recognised by endogenous protein
      prenyltransferases. These uncoupled mutants can now be used as starting points
      for the systematic engineering of the eukaryotic protein prenylation machinery. 

PMID- 25768004
TI  - Immunization with an autotransporter protein of Orientia tsutsugamushi provides
      protective immunity against scrub typhus.
AB  - BACKGROUND: Scrub typhus is an acute febrile disease caused by Orientia
      tsutsugamushi infection. Recently, the rapid increase of scrub typhus incidence
      in several countries within the endemic region has become a serious public health
      issue. Despite the wide range of preventative approaches that have been attempted
      in the past 70 years, all have failed to develop an effective prophylactic
      vaccine. Currently, the selection of the proper antigens is one of the critical
      barriers to generating cross-protective immunity against antigenically-variable
      strains of O. tsutsugamushi. METHODOLOGY/PRINCIPAL FINDINGS: We examined the
      potential role of ScaA protein, an autotransporter protein of O. tsutsugamushi,
      in bacterial pathogenesis and evaluated the protective attributes of ScaA
      immunization in lethal O. tsutsugamushi infection in mice. Our findings
      demonstrate that ScaA functions as a bacterial adhesion factor, and anti-ScaA
      antibody significantly neutralizes bacterial infection of host cells. In
      addition, immunization with ScaA not only provides protective immunity against
      lethal challenges with the homologous strain, but also confers significant
      protection against heterologous strains when combined with TSA56, a major outer
      membrane protein of O. tsutsugamushi. CONCLUSIONS/SIGNIFICANCE: Immunization of
      ScaA proteins provides protective immunity in mice when challenged with the
      homologous strain and significantly enhanced protective immunity against
      infection with heterologous strains. To our knowledge, this is the most promising
      result of scrub typhus vaccination trials against infection of heterologous
      strains in mouse models thus far.

PMID- 25768005
TI  - Schistosoma haematobium infection and CD4+ T-cell levels: a cross-sectional study
      of young South African women.
AB  - Schistosoma (S.) haematobium causes urogenital schistosomiasis and has been
      hypothesized to adversely impact HIV transmission and progression. On the other
      hand it has been hypothesized that HIV could influence the manifestations of
      schistosomiasis. In this cross-sectional study, we explored the association
      between urogenital S. haematobium infection and CD4 cell counts in 792 female
      high-school students from randomly selected schools in rural KwaZulu-Natal, South
      Africa. We also investigated the association between low CD4 cell counts in HIV
      positive women and the number of excreted schistosome eggs in urine. Sixteen
      percent were HIV positive and 31% had signs of urogenital schistosomiasis (as
      determined by genital sandy patches and / or abnormal blood vessels on ectocervix
      / vagina by colposcopy or presence of eggs in urine). After stratifying for HIV
      status, participants with and without urogenital schistosomiasis had similar CD4
      cell counts. Furthermore, there was no significant difference in prevalence of
      urogenital schistosomiasis in HIV positive women with low and high CD4 cell
      counts. There was no significant difference in the number of eggs excreted in
      urine when comparing HIV positive and HIV negative women. Our findings indicate
      that urogenital schistosomiasis do not influence the number of circulating CD4
      cells. 

PMID- 25768006
TI  - Gender-based differences on the association between salt-sensitive genes and
      obesity in Korean children aged between 8 and 9 years.
AB  - BACKGROUND: High sodium intake is associated with the development of chronic
      diseases such as obesity. Although its role in obesity remains controversial,
      there may be a correlation between salt sensitivity and the early onset of
      chronic diseases in obese children. METHODS: In all, 2,163 Korean children (1,106
      boys and 1,057 girls) aged 8-9 years were recruited from seven elementary schools
      in Seoul. To evaluate whether obesity risk was modulated by the salt sensitivity,
      11 SNPs related to salt sensitive genes (SSG) became the target of sodium intakes
      in obese children. RESULTS: BP, HOMA-IR, LDLc, TG, and the girls' sodium intake
      significantly increased, but HDLc significantly decreased with increase in BMI.
      Regardless of sex, the obesity risk was 5.27-fold (CI; 1.320-27.560) higher in
      the Q2 to Q5 of sodium intake adjusted by energy (4044.9-5058.9 mg/day) than in
      the lowest Q1 level (2287.6 mg/day) in obese children. BP was sensitively
      dependent on insulin resistance and lipid accumulation in all subjects; however,
      sodium intake may be an independent risk factor of obesity without increasing BP
      in girls. GRK4 A486V mutant homozygote was highly distributed in the obese group,
      but other SNPs had no impact. The obesity risk increased 7.06, 16.8, and 46.09
      fold more in boys with GRK4 A486V, ACE, and SLC12A3 mutants as sodium intake
      increased. Among girls, the obesity risk increased in GRK4 A486V heterozygote and
      CYP11beta-2 mutant homozygote although sodium intake was relatively lower,
      implying that ACE, SLC12A, CYP11beta-2, and GRK4 A486V polymorphisms showed
      gender-based differences with regard to interaction between sodium intake and
      obesity. CONCLUSION: A high sodium intake markedly increased the obesity risk in
      variants of GRK4 A486V regardless of sex. The obesity risk increased with GRK4
      A486V, ACE, and SLC12A3 variants in boys, whereas it increased with GRK4 A486V
      and CYP11B2 variants in girls as sodium intake increased. Obese children with the
      specific gene variants are recommended to reduce their sodium intake.

PMID- 25768007
TI  - Improved protocol for rapid identification of certain spa types using high
      resolution melting curve analysis.
AB  - Methicillin-resistant Staphylococcus aureus is one of the most significant
      pathogens associated with health care. For efficient surveillance, control and
      outbreak investigation, S. aureus typing is essential. A high resolution melting
      curve analysis was developed and evaluated for rapid identification of the most
      frequent spa types found in an Austrian hospital consortium covering 2,435 beds.
      Among 557 methicillin-resistant Staphylococcus aureus isolates 38 different spa
      types were identified by sequence analysis of the hypervariable region X of the
      protein A gene (spa). Identification of spa types through their characteristic
      high resolution melting curve profiles was considerably improved by double
      spiking with genomic DNA from spa type t030 and spa type t003 and allowed
      unambiguous and fast identification of the ten most frequent spa types t001
      (58%), t003 (12%), t190 (9%), t041 (5%), t022 (2%), t032 (2%), t008 (2%), t002
      (1%), t5712 (1%) and t2203 (1%), representing 93% of all isolates within this
      hospital consortium. The performance of the assay was evaluated by testing
      samples with unknown spa types from the daily routine and by testing three
      different high resolution melting curve analysis real-time PCR instruments. The
      ten most frequent spa types were identified from all samples and on all
      instruments with 100% specificity and 100% sensitivity. Compared to classical spa
      typing by sequence analysis, this gene scanning assay is faster, cheaper and can
      be performed in a single closed tube assay format. Therefore it is an optimal
      screening tool to detect the most frequent endemic spa types and to exclude non
      endemic spa types within a hospital. 

PMID- 25768008
TI  - A cost-effectiveness analysis of a program to control rheumatic fever and
      rheumatic heart disease in Pinar del Rio, Cuba.
AB  - BACKGROUND: Acute rheumatic fever (ARF) and rheumatic heart disease (RHD) persist
      in many low- and middle-income countries. To date, the cost-effectiveness of
      population-based, combined primary and secondary prevention strategies has not
      been assessed. In the Pinar del Rio province of Cuba, a comprehensive ARF/RHD
      control program was undertaken over 1986-1996. The present study analyzes the
      cost-effectiveness of this Cuban program. METHODS AND FINDINGS: We developed a
      decision tree model based on the natural history of ARF/RHD, comparing the costs
      and effectiveness of the 10-year Cuban program to a "do nothing" approach. Our
      population of interest was the cohort of children aged 5-24 years resident in
      Pinar del Rio in 1986. We assessed costs and health outcomes over a lifetime
      horizon, and we took the healthcare system perspective on costs but did not apply
      a discount rate. We used epidemiologic, clinical, and direct medical cost inputs
      that were previously collected for publications on the Cuban program. We
      estimated health gains as disability-adjusted life years (DALYs) averted using
      standard approaches developed for the Global Burden of Disease studies. Cost
      effectiveness acceptability thresholds were defined by one and three times per
      capita gross domestic product per DALY averted. We also conducted an uncertainty
      analysis using Monte Carlo simulations and several scenario analyses exploring
      the impact of alternative assumptions about the program's effects and costs. We
      found that, compared to doing nothing, the Cuban program averted 5051 DALYs (1844
      per 100,000 school-aged children) and saved $7,848,590 (2010 USD) despite a total
      program cost of $202,890 over 10 years. In the scenario analyses, the program
      remained cost saving when a lower level of effectiveness and a reduction in
      averted years of life lost were assumed. In a worst-case scenario including 20
      fold higher costs, the program still had a 100% of being cost-effective and an
      85% chance of being cost saving. CONCLUSIONS: A 10-year program to control
      ARF/RHD in Pinar del Rio, Cuba dramatically reduced morbidity and premature
      mortality in children and young adults and was cost saving. The results of our
      analysis were robust to higher program costs and more conservative assumptions
      about the program's effectiveness. It is possible that the program's
      effectiveness resulted from synergies between primary and secondary prevention
      strategies. The findings of this study have implications for non-communicable
      disease policymaking in other resource-limited settings.

PMID- 25768009
TI  - The impact of tumor nitric oxide production on VEGFA expression and tumor growth
      in a zebrafish rat glioma xenograft model.
AB  - To investigate the effect of nitric oxide on tumor development, we established a
      rat tumor xenograft model in zebrafish embryos. The injected tumor cells formed
      masses in which nitric oxide production could be detected by the use of the cell
      permeant DAF-FM-DA (diaminofluorophore 4-amino-5-methylamino-2'-7'
      difluorofluorescein diacetate) and DAR-4M-AM (diaminorhodamine-4M). This method
      revealed that nitric oxide production could be co-localized with the tumor
      xenograft in 46% of the embryos. In 85% of these embryos, tumors were
      vascularized and blood vessels were observed on day 4 post injection.
      Furthermore, we demonstrated by qRT-PCR that the transplanted glioma cells highly
      expressed Nos2, Vegfa and Cyclin D1 mRNA. In the xenografted embryos we also
      found increased zebrafish vegfa expression. Glioma and zebrafish derived Vegfa
      and tumor Cyclin D1 expression could be down regulated by the nitric oxide
      scavenger 2-(4-Carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide or
      CPTIO. We conclude that even if there is a heterogeneous nitric oxide production
      by the xenografted glioma cells that impacts Vegfa and Cyclin D1 expression
      levels, our results suggest that reduction of nitric oxide levels by nitric oxide
      scavenging could be an efficient approach to treat glioma. 

PMID- 25768010
TI  - Altered spontaneous brain activity in patients with acute spinal cord injury
      revealed by resting-state functional MRI.
AB  - BACKGROUND: Previous neuroimaging studies have provided evidence of structural
      and functional reorganization of brain in patients with chronic spinal cord
      injury (SCI). However, it remains unknown whether the spontaneous brain activity
      changes in acute SCI. In this study, we investigated intrinsic brain activity in
      acute SCI patients using a regional homogeneity (ReHo) analysis based on resting
      state functional magnetic resonance imaging. METHODS: A total of 15 patients with
      acute SCI and 16 healthy controls participated in the study. The ReHo value was
      used to evaluate spontaneous brain activity, and voxel-wise comparisons of ReHo
      were performed to identify brain regions with altered spontaneous brain activity
      between groups. We also assessed the associations between ReHo and the clinical
      scores in brain regions showing changed spontaneous brain activity. RESULTS:
      Compared with the controls, the acute SCI patients showed decreased ReHo in the
      bilateral primary motor cortex/primary somatosensory cortex, bilateral
      supplementary motor area/dorsal lateral prefrontal cortex, right inferior frontal
      gyrus, bilateral dorsal anterior cingulate cortex and bilateral caudate; and
      increased ReHo in bilateral precuneus, the left inferior parietal lobe, the left
      brainstem/hippocampus, the left cingulate motor area, bilateral insula, bilateral
      thalamus and bilateral cerebellum. The average ReHo values of the left thalamus
      and right insula were negatively correlated with the international standards for
      the neurological classification of spinal cord injury motor scores. CONCLUSION:
      Our findings indicate that acute distant neuronal damage has an immediate impact
      on spontaneous brain activity. In acute SCI patients, the ReHo was prominently
      altered in brain regions involved in motor execution and cognitive control,
      default mode network, and which are associated with sensorimotor compensatory
      reorganization. Abnormal ReHo values in the left thalamus and right insula could
      serve as potential biomarkers for assessment of neuronal damage and the
      prediction of clinical outcomes in acute SCI.

PMID- 25768011
TI  - NOD/SCID-GAMMA mice are an ideal strain to assess the efficacy of therapeutic
      agents used in the treatment of myeloma bone disease.
AB  - Animal models of multiple myeloma vary in terms of consistency of onset, degree
      of tumour burden and degree of myeloma bone disease. Here we describe five pre
      clinical models of myeloma in NOD/SCID-GAMMA mice to specifically study the
      effects of therapeutic agents on myeloma bone disease. Groups of 7-8 week old
      female irradiated NOD/SCID-GAMMA mice were injected intravenously via the tail
      vein with either 1x106 JJN3, U266, XG-1 or OPM-2 human myeloma cell lines or
      patient-derived myeloma cells. At the first signs of morbidity in each tumour
      group all animals were sacrificed. Tumour load was measured by histological
      analysis, and bone disease was assessed by micro-CT and standard
      histomorphometric methods. Mice injected with JJN3, U266 or OPM-2 cells showed
      high tumour bone marrow infiltration of the long bones with low variability,
      resulting in osteolytic lesions. In contrast, mice injected with XG-1 or patient
      derived myeloma cells showed lower tumour bone marrow infiltration and less bone
      disease with high variability. Injection of JJN3 cells into NOD/SCID-GAMMA mice
      resulted in an aggressive, short-term model of myeloma with mice exhibiting signs
      of morbidity 3 weeks later. Treating these mice with zoledronic acid at the time
      of tumour cell injection or once tumour was established prevented JJN3-induced
      bone disease but did not reduce tumour burden, whereas, carfilzomib treatment
      given once tumour was established significantly reduced tumour burden. Injection
      of U266, XG-1, OPM-2 and patient-derived myeloma cells resulted in less
      aggressive longer-term models of myeloma with mice exhibiting signs of morbidity
      8 weeks later. Treating U266-induced disease with zoledronic acid prevented the
      formation of osteolytic lesions and trabecular bone loss as well as reducing
      tumour burden whereas, carfilzomib treatment only reduced tumour burden. In
      summary, JJN3, U266 or OPM-2 cells injected into NOD/SCID-GAMMA mice provide
      robust models to study anti-myeloma therapies, particularly those targeting
      myeloma bone disease. 

PMID- 25768012
TI  - The effect on the transcriptome of Anemone coronaria following infection with
      rust (Tranzschelia discolor).
AB  - In order to understand plant/pathogen interaction, the transcriptome of
      uninfected (1S) and infected (2I) plant was sequenced at 3'end by the GS FLX 454
      platform. De novo assembly of high-quality reads generated 27,231 contigs leaving
      37,191 singletons in the 1S and 38,393 in the 2I libraries. ESTcalc tool
      suggested that 71% of the transcriptome had been captured, with 99% of the genes
      present being represented by at least one read. Unigene annotation showed that
      50.5% of the predicted translation products shared significant homology with
      protein sequences in GenBank. In all 253 differential transcript abundance (DTAs)
      were in higher abundance and 52 in lower abundance in the 2I library. 128 higher
      abundance DTA genes were of fungal origin and 49 were clearly plant sequences. A
      tBLASTn-based search of the sequences using as query the full length predicted
      polypeptide product of 50 R genes identified 16 R gene products. Only one R gene
      (PGIP) was up-regulated. The response of the plant to fungal invasion included
      the up-regulation of several pathogenesis related protein (PR) genes involved in
      JA signaling and other genes associated with defense response and down regulation
      of cell wall associated genes, non-race-specific disease resistance1 (NDR1) and
      other genes like myb, presqualene diphosphate phosphatase (PSDPase), a UDP
      glycosyltransferase 74E2-like (UGT). The DTA genes identified here should provide
      a basis for understanding the A. coronaria/T. discolor interaction and leads for
      biotechnology-based disease resistance breeding. 

PMID- 25768013
TI  - Early onset of hypersynchronous network activity and expression of a marker of
      chronic seizures in the Tg2576 mouse model of Alzheimer's disease.
AB  - Cortical and hippocampal hypersynchrony of neuronal networks seems to be an early
      event in Alzheimer's disease pathogenesis. Many mouse models of the disease also
      present neuronal network hypersynchrony, as evidenced by higher susceptibility to
      pharmacologically-induced seizures, electroencephalographic seizures accompanied
      by spontaneous interictal spikes and expression of markers of chronic seizures
      such as neuropeptide Y ectopic expression in mossy fibers. This network
      hypersynchrony is thought to contribute to memory deficits, but whether it
      precedes the onset of memory deficits or not in mouse models remains unknown. The
      earliest memory impairments in the Tg2576 mouse model of Alzheimer's disease have
      been observed at 3 months of age. We thus assessed network hypersynchrony in
      Tg2576 and non-transgenic male mice at 1.5, 3 and 6 months of age. As soon as 1.5
      months of age, Tg2576 mice presented higher seizure susceptibility to systemic
      injection of a GABAA receptor antagonist. They also displayed spontaneous
      interictal spikes on EEG recordings. Some Tg2576 mice presented hippocampal
      ectopic expression of neuropeptide Y which incidence seems to increase with age
      among the Tg2576 population. Our data reveal that network hypersynchrony appears
      very early in Tg2576 mice, before any demonstrated memory impairments. 

PMID- 25768014
TI  - Diversity and antioxidant activity of culturable endophytic fungi from alpine
      plants of Rhodiola crenulata, R. angusta, and R. sachalinensis.
AB  - Rhodiola spp. are rare and endangered alpine plants widely used as medicines and
      food additives by many civilizations since ancient times. Their main effective
      ingredients (such as salidroside and p-tyrosol) are praised to exhibit
      pharmacologic effects on high-altitude sickness and possess anti-aging and other
      adaptogenic capacities based on their antioxidant properties. In this study, 347
      endophytic fungi were isolated from R. crenulata, R. angusta, and R.
      sachalinensis, and the molecular diversity and antioxidant activities of these
      fungi were investigated for the first time. These fungi were categorized into 180
      morphotypes based on cultural characteristics, and their rRNA gene ITS sequences
      were analyzed by BLAST search in the GenBank database. Except for 12 unidentified
      fungi (6.67%), all others were affiliated to at least 57 genera in 20 orders of
      four phyla, namely, Ascomycota (88.89%), Basidiomycota (2.78%), Zygomycota
      (1.11%), and Glomeromycota (0.56%), which exhibited high abundance and diversity.
      Antioxidant assay showed that the DPPH radical-scavenging rates of 114 isolates
      (63.33%) were >50%, and those of five isolates (Rct45, Rct63, Rct64, Rac76, and
      Rsc57) were >90%. The EC50 values of five antioxidant assays suggested
      significant potential of these fungi on scavenging DPPH*, O2-*, and OH* radicals,
      as well as scavenging nitrite and chelating Fe2+, which showed preference and
      selection between endophytic fungi and their hosts. Further research also
      provided the first evidence that Rac12 could produce salidrosides and p-tyrosol.
      Results suggested that versatile endophytic fungi associated with Rhodiola known
      as antioxidants could be exploited as potential sources of novel antioxidant
      products. 

PMID- 25768015
TI  - Factors associated with malaria parasitemia, anemia and serological responses in
      a spectrum of epidemiological settings in Uganda.
AB  - BACKGROUND: Understanding the current epidemiology of malaria and the
      relationship between intervention coverage, transmission intensity, and burden of
      disease is important to guide control activities. We aimed to determine the
      prevalence of anemia, parasitemia, and serological responses to P. falciparum
      antigens, and factors associated with these indicators, in three different
      epidemiological settings in Uganda. METHODS AND FINDINGS: In 2012, cross
      sectional surveys were conducted in 200 randomly selected households from each of
      three sites: Walukuba, Jinja district (peri-urban); Kihihi, Kanungu district
      (rural); and Nagongera, Tororo district (rural) with corresponding estimates of
      annual entomologic inoculation rates (aEIR) of 3.8, 26.6, and 125.0,
      respectively. Of 2737 participants, laboratory testing was done in 2227 (81.4%),
      including measurement of hemoglobin, parasitemia using microscopy, and
      serological responses to P. falciparum apical membrane antigen 1 (AMA-1) and
      merozoite surface protein 1, 19 kilodalton fragment (MSP-119). Analysis of
      laboratory results was restricted to 1949 (87.5%) participants aged <= 40 years.
      Prevalence of anemia (hemoglobin < 11.0 g/dL) was significantly higher in
      Walukuba (18.9%) and Nagongera (17.4%) than in Kihihi (13.1%), and was strongly
      associated with decreasing age for those <= 5 years at all sites. Parasite
      prevalence was significantly higher in Nagongera (48.3%) than in Walukuba (12.2%)
      and Kihihi (12.8%), and significantly increased with age to 11 years, and then
      significantly decreased at all sites. Seropositivity to AMA-1 was 53.3% in
      Walukuba, 63.0% in Kihihi, and 83.7% in Nagongera and was associated with
      increasing age at all sites. AMA-1 seroconversion rates strongly correlated with
      transmission intensity, while serological responses to MSP-119 did not.
      CONCLUSION: Anemia was predominant in young children and parasitemia peaked by 11
      years across 3 sites with varied transmission intensity. Serological responses to
      AMA-1 appeared to best reflect transmission intensity, and may be a more accurate
      indicator for malaria surveillance than anemia or parasitemia.

PMID- 25768016
TI  - Differences in type I interferon signaling antagonism by dengue viruses in human
      and non-human primate cell lines.
AB  - BACKGROUND/OBJECTIVES: In vitro studies have shown that dengue virus (DENV) can
      thwart the actions of interferon (IFN)-alpha/beta and prevent the development of
      an antiviral state in infected cells. Clinical studies looking at gene expression
      in patients with severe dengue show a reduced expression of interferon stimulated
      genes compared to patients with dengue fever. Interestingly, there are
      conflicting reports as to the ability of DENV or other flaviviruses to inhibit
      IFN-alpha/beta signaling. METHODOLOGY/PRINCIPAL FINDINGS: In order to determine
      the relative inhibition of IFN-alpha/beta signaling by DENVs, a method combining
      flow cytometry and a four-parameter logistic regression model was established. A
      representative isolate from DENV-1, -3 and -4 and seventeen representative
      isolates encompassing all DENV-2 genotypes were evaluated. All of the DENVs
      evaluated in this study were capable of inhibiting IFN-alpha/beta signaling. Most
      of the strains were able to inhibit IFN-alpha/beta to a degree similar to DENV
      strain 16681; however, DENV-2 sylvatic strains demonstrated an increased
      inhibition of phosphorylated signal transducer and activator of transcription
      (pSTAT1). Surprisingly, we were unable to observe inhibition of pSTAT1 by DENV-2
      sylvatic strains or the Asian strain 16681 in non-human primate (NHP) cell lines.
      Analysis in primary Rhesus macaque dendritic cells suggests that DENVs are
      capable of inhibiting IFN signaling in these cells. However, contrary to human
      dendritic cells, production of IFN-alpha was detected in the supernatant of DENV
      infected Rhesus macaque dendritic cells. CONCLUSIONS: The ability of DENVs to
      inhibit IFN-alpha/beta signaling is conserved. Although some variation in the
      inhibition was observed, the moderate differences may be difficult to correlate
      with clinical outcomes. DENVs were unable to inhibit pSTAT1 in NHP cell lines,
      but their ability to inhibit pSTAT1 in primary Rhesus macaque dendritic cells
      suggests that this may be a cell specific phenomena or due to the transformed
      nature of the cell lines.

PMID- 25768017
TI  - The ATM signaling cascade promotes recombination-dependent pachytene arrest in
      mouse spermatocytes.
AB  - Most mutations that compromise meiotic recombination or synapsis in mouse
      spermatocytes result in arrest and apoptosis at the pachytene stage of the first
      meiotic prophase. Two main mechanisms are thought to trigger arrest: one
      independent of the double-strand breaks (DSBs) that initiate meiotic
      recombination, and another activated by persistent recombination intermediates.
      Mechanisms underlying the recombination-dependent arrest response are not well
      understood, so we sought to identify factors involved by examining mutants
      deficient for TRIP13, a conserved AAA+ ATPase required for the completion of
      meiotic DSB repair. We find that spermatocytes with a hypomorphic Trip13 mutation
      (Trip13mod/mod) arrest with features characteristic of early pachynema in wild
      type, namely, fully synapsed chromosomes without incorporation of the histone
      variant H1t into chromatin. These cells then undergo apoptosis, possibly in
      response to the arrest or in response to a defect in sex body formation. However,
      TRIP13-deficient cells that additionally lack the DSB-responsive kinase ATM
      progress further, reaching an H1t-positive stage (i.e., similar to mid/late
      pachynema in wild type) despite the presence of unrepaired DSBs. TRIP13-deficient
      spermatocytes also progress to an H1t-positive stage if ATM activity is
      attenuated by hypomorphic mutations in Mre11 or Nbs1 or by elimination of the ATM
      effector kinase CHK2. These mutant backgrounds nonetheless experience an
      apoptotic block to further spermatogenic progression, most likely caused by
      failure to form a sex body. DSB numbers are elevated in Mre11 and Nbs1 hypomorphs
      but not Chk2 mutants, thus delineating genetic requirements for the ATM-dependent
      negative feedback loop that regulates DSB numbers. The findings demonstrate for
      the first time that ATM-dependent signaling enforces the normal pachytene
      response to persistent recombination intermediates. Our work supports the
      conclusion that recombination defects trigger spermatocyte arrest via pathways
      than are genetically distinct from sex body failure-promoted apoptosis and
      confirm that the latter can function even when recombination-dependent arrest is
      inoperative. Implications of these findings for understanding the complex
      relationships between spermatocyte arrest and apoptosis are discussed. 

PMID- 25768020
TI  - Correction: Knowledge retrieval from PubMed abstracts and electronic medical
      records with the multiple sclerosis ontology.

PMID- 25768018
TI  - Increased plasma levels of heat shock protein 70 associated with subsequent
      clinical conversion to mild cognitive impairment in cognitively healthy elderly.
AB  - BACKGROUND AND AIMS: Heat shock proteins (HSPs) have been regarded as
      cytoprotectants that protect brain cells during the progression of
      neurodegenerative diseases and from damage resulting from cerebral ischemia. In
      this study, we assessed the association between plasma HSP 70/27 levels and
      cognitive decline. METHODS: Among participants in the community-based cohort
      study of dementia called the Gwangju Dementia and Mild Cognitive Impairment
      Study, subjects without cognitive impairment at baseline, who then either
      remained without impairment (non-conversion group), or suffered mild cognitive
      impairment (MCI) (conversion group) (non-conversion group, N = 36; conversion
      group, N = 30) were analyzed. RESULTS: After a five to six year follow-up period,
      comparison of the plasma HSP 70 and HSP 27 levels of the two groups revealed that
      only the plasma HSP 70 level was associated with a conversion to MCI after
      adjustments for age, gender, years of education, follow-up duration, APOE e4,
      hypertension, and diabetes (repeated measure analysis of variance: F = 7.59, p =
      0.008). Furthermore, an increase in plasma HSP 70 level was associated with
      cognitive decline in language and executive function (linear mixed model: Korean
      Boston Naming Test, -0.426 [-0.781, -0.071], p = 0.019; Controlled Oral Word
      Association Test, -0.176 [-0.328, -0.023], p = 0.024; Stroop Test, -0.304 [
      0.458, -0.150], p<0.001). CONCLUSIONS: These findings suggest that the plasma HSP
      70 level may be related to cognitive decline in the elderly.

PMID- 25768019
TI  - Effect of fatty acids on human bone marrow mesenchymal stem cell energy
      metabolism and survival.
AB  - Successful stem cell therapy requires the optimal proliferation, engraftment, and
      differentiation of stem cells into the desired cell lineage of tissues. However,
      stem cell therapy clinical trials to date have had limited success, suggesting
      that a better understanding of stem cell biology is needed. This includes a
      better understanding of stem cell energy metabolism because of the importance of
      energy metabolism in stem cell proliferation and differentiation. We report here
      the first direct evidence that human bone marrow mesenchymal stem cell (BMMSC)
      energy metabolism is highly glycolytic with low rates of mitochondrial oxidative
      metabolism. The contribution of glycolysis to ATP production is greater than 97%
      in undifferentiated BMMSCs, while glucose and fatty acid oxidation combined only
      contribute 3% of ATP production. We also assessed the effect of physiological
      levels of fatty acids on human BMMSC survival and energy metabolism. We found
      that the saturated fatty acid palmitate induces BMMSC apoptosis and decreases
      proliferation, an effect prevented by the unsaturated fatty acid oleate.
      Interestingly, chronic exposure of human BMMSCs to physiological levels of
      palmitate (for 24 hr) reduces palmitate oxidation rates. This decrease in
      palmitate oxidation is prevented by chronic exposure of the BMMSCs to oleate.
      These results suggest that reducing saturated fatty acid oxidation can decrease
      human BMMSC proliferation and cause cell death. These results also suggest that
      saturated fatty acids may be involved in the long-term impairment of BMMSC
      survival in vivo. 

PMID- 25768021
TI  - Comparative metabolic analysis of CHO cell clones obtained through cell
      engineering, for IgG productivity, growth and cell longevity.
AB  - Cell engineering has been used to improve animal cells' central carbon
      metabolism. Due to the central carbon metabolism's inefficiency and limiting
      input of carbons into the TCA cycle, key reactions belonging to these pathways
      have been targeted to improve cultures' performance. Previous works have shown
      the positive effects of overexpressing PYC2, MDH II and fructose transporter.
      Since each of these modifications was performed in different cell lines and
      culture conditions, no comparisons between these modifications can be made. In
      this work we aim at contrasting the effect of each of the modifications by
      comparing pools of transfected IgG producing CHO cells cultivated in batch
      cultures. Results of the culture performance of engineered clones indicate that
      even though all studied clones had a more efficient metabolism, not all of them
      showed the expected improvement on cell proliferation and/or specific
      productivity. CHO cells overexpressing PYC2 were able to improve their
      exponential growth rate but IgG synthesis was decreased, MDH II overexpression
      lead to a reduction in cell growth and protein production, and cells transfected
      with the fructose transporter gene were able to increase cell density and reach
      the same volumetric protein production as parental CHO cells in glucose. We
      propose that a redox unbalance caused by the new metabolic flux distribution
      could affect IgG assembly and protein secretion. In addition to reaction
      dynamics, thermodynamic aspects of metabolism are also discussed to further
      understand the effect of these modifications over central carbon metabolism. 

PMID- 25768022
TI  - Uncovering the nutritional landscape of food.
AB  - Recent progresses in data-driven analysis methods, including network-based
      approaches, are revolutionizing many classical disciplines. These techniques can
      also be applied to food and nutrition, which must be studied to design healthy
      diets. Using nutritional information from over 1,000 raw foods, we systematically
      evaluated the nutrient composition of each food in regards to satisfying daily
      nutritional requirements. The nutrient balance of a food was quantified and
      termed nutritional fitness; this measure was based on the food's frequency of
      occurrence in nutritionally adequate food combinations. Nutritional fitness
      offers a way to prioritize recommendable foods within a global network of foods,
      in which foods are connected based on the similarities of their nutrient
      compositions. We identified a number of key nutrients, such as choline and alpha
      linolenic acid, whose levels in foods can critically affect the nutritional
      fitness of the foods. Analogously, pairs of nutrients can have the same effect.
      In fact, two nutrients can synergistically affect the nutritional fitness,
      although the individual nutrients alone may not have an impact. This result,
      involving the tendency among nutrients to exhibit correlations in their
      abundances across foods, implies a hidden layer of complexity when exploring for
      foods whose balance of nutrients within pairs holistically helps meet nutritional
      requirements. Interestingly, foods with high nutritional fitness successfully
      maintain this nutrient balance. This effect expands our scope to a diverse
      repertoire of nutrient-nutrient correlations, which are integrated under a common
      network framework that yields unexpected yet coherent associations between
      nutrients. Our nutrient-profiling approach combined with a network-based analysis
      provides a more unbiased, global view of the relationships between foods and
      nutrients, and can be extended towards nutritional policies, food marketing, and
      personalized nutrition. 

PMID- 25768023
TI  - Telecare for diabetes, CHF or COPD: effect on quality of life, hospital use and
      costs. A randomised controlled trial and qualitative evaluation.
AB  - OBJECTIVES: To assess the effect of telecare on health related quality of life,
      self-care, hospital use, costs and the experiences of patients, informal carers
      and health care professionals. METHODS: Patients were randomly assigned either to
      usual care or to additionally entering their data into a commercially-available
      electronic device that uploaded data once a day to a nurse-led monitoring
      station. Patients had congestive heart failure (Site A), chronic obstructive
      pulmonary disease (Site B), or any long-term condition, mostly diabetes (Site C).
      Site C contributed only intervention patients - they considered a usual care
      option to be unethical. The study took place in New Zealand between September
      2010 and February 2012, and lasted 3 to 6 months for each patient. The primary
      outcome was health-related quality of life (SF36). Data on experiences were
      collected by individual and group interviews and by questionnaire. RESULTS: There
      were 171 patients (98 intervention, 73 control). Quality of life, self-efficacy
      and disease-specific measures did not change significantly, while anxiety and
      depression both decreased significantly with the intervention. Hospital
      admissions, days in hospital, emergency department visits, outpatient visits and
      costs did not differ significantly between the groups. Patients at all sites were
      universally positive. Many felt safer and more cared-for, and said that they and
      their family had learned more about managing their condition. Staff could all see
      potential benefits of telecare, and, after some initial technical problems, many
      staff felt that telecare enabled them to effectively monitor more patients.
      CONCLUSIONS: Strongly positive patient and staff experiences and attitudes
      complement and contrast with small or non-significant quantitative changes.
      Telecare led to patients and families taking a more active role in self
      management. It is likely that subgroups of patients benefitted in ways that were
      not measured or visible within the quantitative data, especially feelings of
      safety and being cared-for. TRIAL REGISTRATION: Australian New Zealand Clinical
      Trials Registry ACTRN12610000269033.

PMID- 25768024
TI  - Association of histamine N-methyltransferase Thr105Ile polymorphism with
      Parkinson's disease and schizophrenia in Han Chinese: a case-control study.
AB  - Parkinson's disease (PD) and schizophrenia (SCZ) are frequent central nervous
      disorders that have unclear etiologies but that show similarities in their
      pathogenesis. Since elevated histamine levels in the brain have been associated
      with PD and SCZ, we wanted to explore whether the Thr105Ile substitution in the
      histamine N-methyltransferase gene (HNMT-Thr105Ile), which impairs histamine
      degradation, is associated with either disease. We used the ligase detection
      reaction to genotype a case-control cohort of Han Chinese patients with PD or SCZ
      and healthy controls at the HNMT-Thr105Ile locus. The Ile allele was associated
      with reduced risk of PD (OR 0.516, 95% CI 0.318 to 0.838, p = 0.007) and of SCZ
      (OR 0.499, 95% CI 0.288 to 0.865, p = 0.011). Genotype frequencies and minor
      allele frequencies were similar between patients and controls when we compared
      males with females or early-onset patients with late-onset ones. Genotype and
      allele frequencies were not significantly different between PD patients with
      dyskinesia and PD patients without dyskinesia. Our results suggest that the
      heterozygous Thr/Ile genotype at the HNMT-Thr105Ile locus and the minor Ile105
      allele protect against PD and SCZ in Han Chinese.

PMID- 25768026
TI  - Treatment of Perimembranous Ventricular Septal Defect in Children Weighing Less
      than 15 kg: Minimally Invasive Periventricular Device Occlusion versus Right
      Subaxillary Small Incision Surgical Repair.
AB  - BACKGROUND: To compare the treatment outcomes between minimally invasive
      periventricular device occlusion (MIPDO) and right subaxillary incision surgical
      repair (RSISR) on perimembranous ventricular septal defect (PmVSD) in children
      weighing less than 15 kg. METHODS: From January 2010 to January 2013, 538 infants
      (age < 3 years, weight < 15 kg) with PmVSD were randomly divided into two groups
      according to different treatment methods. Group 1 (265 cases) had periventricular
      device occlusion through a lower partial median sternotomy under transesophageal
      echocardiography (TEE); group 2 (265 cases) underwent surgical repair on
      cardiopulmonary bypass (CPB) through a right subaxillary incision. A prospective
      randomized controlled study was performed regarding success rate, operation time,
      volume of blood loss and transfusion, length of intubation and intensive care
      unit (ICU) stay, complications, expenses, and follow-up results. RESULTS: All
      patients had effective treatment with no death or serious life-threatening
      complications. In group 1, 255 cases (96.23%) underwent successful
      periventricular device occlusion. The remaining 10 cases (3.77%) were
      successfully converted to conventional operation. Different arrhythmias arose in
      30 cases (11.76%), trivial residual shunt (RS) in 18 cases (7.06%), and new
      trivial tricuspid regurgitation (TR) in 29 cases (11.37%). In group 2, all
      patients (100%) underwent successful surgical repair. Different arrhythmias
      occurred in 116 cases (43.77%), trivial RS in 16 cases (6.04%), new trivial TR in
      11 cases (4.15%), and heart dysfunction in 17 patients (6.42%). All patients were
      followed for more than 12 months. The final treatment effects were similar in
      both groups, but group 1 was significantly superior to group 2 regarding
      operation time, volume of blood loss, length of intubation and ICU stay,
      hospitalizations, and costs (all p < 0.05). TR incidence was higher in group 1 (p
      < 0.05), and that of right bundle branch block was higher in group 2 (p < 0.05).
      The incision was longer in group 2, but in a less exposed location. CPB was not
      needed in group 1, but anticoagulants were required for 3 to 6 months.
      CONCLUSION: Both RSISR and MIPDO are effective treatment methods for PmVSD.
      Though having some limitations, MIPDO not only minimized the surgical trauma to
      patients but also ensured safety to the maximum extent. However, patient
      selection is vital. For selected patients, especially those with moderate PmVSDs
      with obvious clinical symptoms and no valve regurgitation, it seems an ideal
      approach.

PMID- 25768025
TI  - Kinetic Analysis and Quantification of [11C]Martinostat for in Vivo HDAC Imaging
      of the Brain.
AB  - Epigenetic mechanisms mediated by histone deacetylases (HDACs) have been
      implicated in a wide-range of CNS disorders and may offer new therapeutic
      opportunities. In vivo evaluation of HDAC density and drug occupancy has become
      possible with [(11)C]Martinostat, which exhibits selectivity for a subset of
      class I/IIb HDAC enzymes. In this study, we characterize the kinetic properties
      of [(11)C]Martinostat in the nonhuman primate (NHP) brain in preparation for
      human neuroimaging studies. The goal of this work was to determine whether
      classic compartmental analysis techniques were appropriate and to further
      determine if arterial plasma is required for future NHP studies. Using an
      arterial plasma input function, several analysis approaches were evaluated for
      robust outcome measurements. [(11)C]Martinostat showed high baseline distribution
      volume (VT) ranging from 29.9 to 54.4 mL/cm(3) in the brain and large changes in
      occupancy (up to 99%) with a blocking dose approaching full enzyme saturation. An
      averaged nondisplaceable tissue uptake (VND) of 8.6 +/- 3.7 mL/cm(3) suggests
      high specific binding of [(11)C]Martinostat. From a two-tissue compartment model,
      [(11)C]Martinostat exhibits a high K1 (averaged K1 of 0.65 mL/cm(3)/min) and a
      small k4 (average of 0.0085 min(-1)). Our study supports that [(11)C]Martinostat
      can be used to detect changes in HDAC density and occupancy in vivo and that
      simplified analysis not using arterial blood could be appropriate. 

PMID- 25768027
TI  - Comparison of Postoperative Pain after Different Thoracic Surgery Approaches as
      Measured by Electrical Stimulation.
AB  - BACKGROUND: Postoperative pain is commonly evaluated using the numerous rating
      scale (NRS), visual analogue scale, or pain scale; however, these assessments are
      easily affected by various subjective factors. We measured the degree of
      postoperative chest pain among different thoracic surgery approaches using NRS
      and electrical stimulation measurements. METHODS: Seventy patients who underwent
      lobectomy or segmentectomy were enrolled. Concomitant with NRS, pain scores were
      quantitatively measured on postoperative day 2 using an electrical
      neurostimulator to compare the degree of pain among three different surgical
      approaches: pure video-assisted thoracic surgery (VATS), hybrid VATS, and
      conventional thoracotomy. The risk factors associated with postoperative pain
      were also analyzed. RESULTS: Thirty patients underwent lung resection with pure
      VATS, while 30 had hybrid VATS, and 10 had conventional thoracotomy. Among the
      three surgical approaches, analyzing the pain score indicated statistically
      significant differences (pure, 159.50 +/- 26.22; hybrid, 269.36 +/- 30.49;
      thoracotomy, 589.40 +/- 141.11; p = 0.003); however, NRS did not obtain a
      statistically significant difference between the three approaches (pure, 4.26 +/-
      0.27; hybrid, 4.96 +/- 0.30; thoracotomy, 5.50 +/- 0.68; p = 0.105). A
      multivariate analysis showed that the surgical approach was an independent risk
      factor for postoperative pain as determined by the pain score (pure vs. hybrid, p
      = 0.076; pure vs. thoracotomy, p < 0.001). CONCLUSION: For lung surgery, the
      differences in surgical approach were an independent risk factor for
      postoperative pain. In the early postoperative period, pure VATS was shown to be
      the least painful of the three surgical approaches.

PMID- 25768028
TI  - A critical study of different Monte Carlo scoring methods of dose average linear
      energy-transfer maps calculated in voxelized geometries irradiated with clinical
      proton beams.
AB  - We compare unrestricted dose average linear energy transfer (LET) maps calculated
      with three different Monte Carlo scoring methods in voxelized geometries
      irradiated with proton therapy beams with three different Monte Carlo scoring
      methods. Simulations were done with the Geant4 (Geometry ANd Tracking) toolkit.
      The first method corresponds to a step-by-step computation of LET which has been
      reported previously in the literature. We found that this scoring strategy is
      influenced by spurious high LET components, which relative contribution in the
      dose average LET calculations significantly increases as the voxel size becomes
      smaller. Dose average LET values calculated for primary protons in water with
      voxel size of 0.2 mm were a factor ~1.8 higher than those obtained with a size of
      2.0 mm at the plateau region for a 160 MeV beam. Such high LET components are a
      consequence of proton steps in which the condensed-history algorithm determines
      an energy transfer to an electron of the material close to the maximum value,
      while the step length remains limited due to voxel boundary crossing. Two
      alternative methods were derived to overcome this problem. The second scores LET
      along the entire path described by each proton within the voxel. The third
      followed the same approach of the first method, but the LET was evaluated at each
      step from stopping power tables according to the proton kinetic energy value. We
      carried out microdosimetry calculations with the aim of deriving reference dose
      average LET values from microdosimetric quantities. Significant differences
      between the methods were reported either with pristine or spread-out Bragg peaks
      (SOBPs). The first method reported values systematically higher than the other
      two at depths proximal to SOBP by about 15% for a 5.9 cm wide SOBP and about 30%
      for a 11.0 cm one. At distal SOBP, the second method gave values about 15% lower
      than the others. Overall, we found that the third method gave the most consistent
      performance since it returned stable dose average LET values against simulation
      parameter changes and gave the best agreement with dose average LET estimations
      from microdosimetry calculations. 

PMID- 25768029
TI  - Grey matter, an endophenotype for schizophrenia? A voxel-based morphometry study
      in siblings of patients with schizophrenia.
AB  - BACKGROUND: Grey matter, both volume and concentration, has been proposed as an
      endophenotype for schizophrenia given a number of reports of grey matter
      abnormalities in relatives of patients with schizophrenia. However, previous
      studies on grey matter abnormalities in relatives have produced inconsistent
      results. The aim of the present study was to examine grey matter differences
      between controls and siblings of patients with schizophrenia and to examine
      whether the age, genetic loading or subclinical psychotic symptoms of selected
      individuals could explain the previously reported inconsistencies. METHODS: We
      compared the grey matter volume and grey matter concentration of healthy siblings
      of patients with schizophrenia and healthy controls matched for age, sex and
      education using voxel-based morphometry (VBM). Furthermore, we selected
      subsamples based on age (< 30 yr), genetic loading and subclinical psychotic
      symptoms to examine whether this would lead to different results. RESULTS: We
      included 89 siblings and 69 controls in our study. The results showed that
      siblings and controls did not differ significantly on grey matter volume or
      concentration. Furthermore, specifically selecting participants based on age,
      genetic loading or subclinical psychotic symptoms did not alter these findings.
      LIMITATIONS: The main limitation was that subdividing the sample resulted in
      smaller samples for the subanalyses. Furthermore, we used MRI data from 2
      different scanner sites. CONCLUSION: These results indicate that grey matter
      measured through VBM might not be a suitable endophenotype for schizophrenia.

PMID- 25768030
TI  - Monocyte and microglial activation in patients with mood-stabilized bipolar
      disorder.
AB  - BACKGROUND: Bipolar disorder is associated with medical comorbidities that have
      been linked to systemic inflammatory mechanisms. There is, however, limited
      evidence supporting a role of neuroinflammation in bipolar disorder. Here we
      tested whether microglial activation and associated tissue remodelling processes
      are related to bipolar disorder by analyzing markers in cerebrospinal fluid (CSF)
      and serum from patients and healthy controls. METHODS: Serum was sampled from
      euthymic patients with bipolar disorder and healthy controls, and CSF was sampled
      from a large subset of these individuals. The levels of monocyte chemoattractant
      protein-1 (MCP-1), YKL-40, soluble cluster of differentiation 14 (sCD14), tissue
      inhibitor of metalloproteinases-1 (TIMP-1) and tissue inhibitor of
      metalloproteinases-2 (TIMP-2), were measured, and we adjusted comparisons between
      patients and controls for confounding factors. RESULTS: We obtained serum samples
      from 221 patients and 112 controls and CSF samples from 125 patients and 87
      controls. We found increased CSF levels of MCP-1 and YKL-40 and increased serum
      levels of sCD14 and YKL-40 in patients compared with controls; these differences
      remained after controlling for confounding factors, such as age, sex, smoking,
      blood-CSF barrier function, acute-phase proteins and body mass index. The CSF
      levels of MCP-1 and YKL-40 correlated with the serum levels, whereas the
      differences between patients and controls in CSF levels of MCP-1 and YKL-40 were
      independent of serum levels. LIMITATIONS: The cross-sectional study design
      precludes conclusions about causality. CONCLUSION: Our results suggest that both
      neuroinflammatory and systemic inflammatory processes are involved in the
      pathophysiology of bipolar disorder. Importantly, markers of immunological
      processes in the brain were independent of peripheral immunological activity.

PMID- 25768032
TI  - Highlights in NSCLC from the 2014 American Society of Clinical Oncology annual
      meeting.

PMID- 25768033
TI  - Highlights in NSCLC from the 2014 ASCO meeting.

PMID- 25768031
TI  - Chimeric rabies virus-like particles containing membrane-anchored GM-CSF enhances
      the immune response against rabies virus.
AB  - Rabies remains an important public health threat in most developing countries. To
      develop a more effective and safe vaccine against rabies, we have constructed a
      chimeric rabies virus-like particle (VLP), which containing glycoprotein (G) and
      matrix protein (M) of rabies virus (RABV) Evelyn-Rokitnicki-Abelseth (ERA)
      strain, and membrane-anchored granulocyte-macrophage colony-stimulating factor
      (GM-CSF), and it was named of EVLP-G. The immunogenicity and protective efficacy
      of EVLP-G against RABV were evaluated by intramuscular administration in a mouse
      model. The EVLP-G was successfully produced in insect cells by coinfection with
      three recombinant baculoviruses expressing G, M, and GM-CSF, respectively. The
      membrane-anchored GM-CSF possesses a strong adjuvant activity. More B cells and
      dendritic cells (DCs) were recruited and/or activated in inguinal lymph nodes in
      mice immunized with EVLP-G. EVLP-G was found to induce a significantly increased
      RABV-specific virus-neutralizing antibody and elicit a larger and broader
      antibody subclass responses compared with the standard rabies VLP (sRVLP,
      consisting of G and M). The EVLP-G also elicited significantly more IFN-gamma- or
      IL-4-secreting CD4+ and CD8+ T cells than the sRVLP. Moreover, the immune
      responses induced by EVLP-G protect all vaccinated mice from lethal challenge
      with RABV. These results suggest that EVLP-G has the potential to be developed as
      a novel vaccine candidate for the prevention and control of animal rabies.

PMID- 25768034
TI  - Analysis of the interaction of surfactants oleic acid and oleylamine with iron
      oxide nanoparticles through molecular mechanics modeling.
AB  - The interface interactions between surfactants oleic acid and oleylamine and
      magnetic nanoparticles are studied via molecular mechanics and dynamics. Mixtures
      of these two surfactants are widely advocated in the chemical synthesis of
      nanoparticles. However, the exact dynamic mechanism remains unclear. Here we
      report, for the first time, a comprehensive qualitative model showing the
      importance of acid-base complex formation between oleic acid and oleylamine as
      well as the presence of free protons in the engineering of nanoparticles of
      specific shapes and sizes. We show why critical parameters such as surfactant
      concentration may modify iron oxide nanoparticle shape and size and how this can
      be understood in the light of acid-base complex pair formation. We report on the
      influence these parameters have on both the in situ nanoparticle surface charge
      and zeta potential. Transmission electron microscopy (TEM), FTIR, and pH studies
      are used to confirm the validity of the calculated binding energies and number of
      acid-base pairs. 

PMID- 25768035
TI  - Accurate fluorescence quantum yield determination by fluorescence correlation
      spectroscopy.
AB  - Here, we present a comparative method for the accurate determination of
      fluorescence quantum yields (QYs) by fluorescence correlation spectroscopy. By
      exploiting the high sensitivity of single-molecule spectroscopy, we obtain the
      QYs of samples in the microliter range and at (sub)nanomolar concentrations.
      Additionally, in combination with fluorescence lifetime measurements, our method
      allows the quantification of both static and collisional quenching constants.
      Thus, besides being simple and fast, our method opens up the possibility to
      photophysically characterize labeled biomolecules under application-relevant
      conditions and with low sample consumption, which is often important in single
      molecule studies. 

PMID- 25768036
TI  - CoMoO4/CuMo0.9W0.1O4 mixture as an efficient piezochromic sensor to detect
      temperature/pressure shock parameters.
AB  - A mixture of two piezochromic compounds can be used as a universal shock
      detector, i.e., to determine the shock pressure without knowing a priori the
      temperature at which the shock occurred. For this purpose, both piezochromic
      compounds must exhibit different temperature influences in their transition
      pressure values. This demonstration uses two piezochromic compounds (CoMoO4 and
      CuMoO4-type oxides) that exhibit a first-order phase transition between their two
      allotropic forms associated with a drastic color change. The colorimetric
      coordinates of the mixture indicate the pressure and temperature of a shock. 

PMID- 25768037
TI  - Band Alignment in WSe2-Graphene Heterostructures.
AB  - Using different types of WSe2 and graphene-based heterostructures, we
      experimentally determine the offset between the graphene neutrality point and the
      WSe2 conduction and valence band edges, as well as the WSe2 dielectric constant
      along the c-axis. In a first heterostructure, consisting of WSe2-on-graphene, we
      use the WSe2 layer as the top dielectric in dual-gated graphene field-effect
      transistors to determine the WSe2 capacitance as a function of thickness, and the
      WSe2 dielectric constant along the c-axis. In a second heterostructure consisting
      of graphene-on-WSe2, the lateral electron transport shows ambipolar behavior
      characteristic of graphene combined with a conductivity saturation at
      sufficiently high positive (negative) gate bias, associated with carrier
      population of the conduction (valence) band in WSe2. By combining the
      experimental results from both heterostructures, we determine the band offset
      between the graphene charge neutrality point, and the WSe2 conduction and valence
      band edges. 

PMID- 25768038
TI  - Food coloring agents and plant food supplements derived from Vitis vinifera: a
      new source of human exposure to ochratoxin A.
AB  - Grape pomaces are increasingly being used as starting material in the industrial
      production of plant food supplements (PFS), food coloring, and tartrates, but
      they are at risk of ochratoxin A (OTA) contamination, a mycotoxin with
      nephrotoxic and carcinogenic effects. We analyzed 24 commercial PFS and 13 food
      coloring samples derived from Vitis vinifera, mainly pomaces, using a HPLC-FLD
      method for OTA determination. OTA was found in 75% of PFS samples and 69% of food
      coloring samples at levels of <1.16-20.23 MUg/kg and <1.16-32.00 MUg/kg,
      respectively. The four commercial leavening agents containing tartrates were
      found to be negative for OTA. All eight samples collected in two distilleries
      that use grape pomaces and wine lees to produce tartrates and other byproducts
      contained OTA at levels of <1.16-240.93 MUg/kg. The high incidence of OTA
      contamination in PFS and food coloring agents derived from V. vinifera suggests
      that maximum permitted level(s) should be established for this mycotoxin in these
      products. 

PMID- 25768040
TI  - Multifunctional dendrimer-entrapped gold nanoparticles modified with RGD peptide
      for targeted computed tomography/magnetic resonance dual-modal imaging of tumors.
AB  - We report the use of multifunctional dendrimer-entrapped gold nanoparticles (Au
      DENPs) loaded with gadolinium (Gd) chelator/Gd(III) complexes and surface
      modified with thiolated cyclo(Arg-Gly-Asp-Phe-Lys(mpa)) (RGD) peptide for
      targeted dual-mode computed tomography (CT)/magnetic resonance (MR) imaging of
      small tumors. In this study, amine-terminated generation 5 poly(amidoamine)
      dendrimers were used as a nanoplatform to be covalently modified with Gd
      chelator, RGD via a polyethylene glycol (PEG) spacer, and PEG monomethyl ether.
      Then the multifunctional dendrimers were used as templates to entrap gold
      nanoparticles, followed by chelating Gd(III) ions and acetylation of the
      remaining dendrimer terminal amines. The thus-formed multifunctional Au DENPs (in
      short, Gd-Au DENPs-RGD) were characterized via different techniques. We show that
      the multifunctional Au DENPs with a Au core size of 3.8 nm are water-dispersible,
      stable under different pH (5-8) and temperature conditions (4-50  degrees C), and
      noncytotoxic at a Au concentration up to 100 MUM. With the displayed X-ray
      attenuation property and the r1 relaxivity (2.643 mM(-1) s(-1)), the developed Gd
      Au DENPs-RGD are able to be used as a dual-mode nanoprobe for targeted CT/MR
      imaging of an alphavbeta3 integrin-overexpressing xenografted small tumor model
      in vivo via RGD-mediated active targeting pathway. The developed multifunctional
      Gd-Au DENPs-RGD may be used as a promising dual-mode nanoprobe for targeted CT/MR
      imaging of different types of alphavbeta3 integrin-overexpressing cancer. 

PMID- 25768041
TI  - Rhodium-catalyzed cyclopropanation of fluorinated olefins: a straightforward
      route to highly functionalized fluorocyclopropanes.
AB  - An efficient access to highly functionalized monofluorocyclopropanes is
      described. The developed methodology allowed straightforward access to a large
      panel of polysubstituted fluorinated cyclopropanes in good to excellent yields
      and good diastereoselectivities. The Rh-catalyzed cyclopropanation proved to be
      efficient on several fluorinated olefins and several diazo compounds. This method
      represents the first general route to complex fluorinated cyclopropanes. 

PMID- 25768039
TI  - Pd(II)-catalyzed C-H functionalizations directed by distal weakly coordinating
      functional groups.
AB  - Ortho-C(sp(2))-H olefination and acetoxylation of broadly useful synthetic
      building blocks phenylacetyl Weinreb amides, esters, and ketones are developed
      without installing an additional directing group. The interplay between the
      distal weak coordination and the ligand-acceleration is crucial for these
      reactions to proceed under mild conditions. The tolerance of longer distance
      between the target C-H bonds and the directing functional groups also allows for
      the functionalizations of more distal C-H bonds in hydrocinnamoyl ketones,
      Weinreb amides, and biphenyl Weinreb amides. Mechanistically, the coordination of
      these carbonyl groups and the bisdentate amino acid ligand with Pd(II) centers
      provides further evidence for our early hypothesis that the carbonyl groups of
      the potassium carboxylate are responsible for the directed C-H activation of
      carboxylic acids. 

PMID- 25768042
TI  - Stable luminescent metal-organic frameworks as dual-functional materials to
      encapsulate ln(3+) ions for white-light emission and to detect nitroaromatic
      explosives.
AB  - A stable porous carbazole-based luminescent metal-organic framework, NENU-522,
      was successfully constructed. It is extremely stable in air and acidic/basic
      aqueous solutions, which provides the strategy for luminescent material
      encapsulation of Ln(3+) ions with tunable luminescence for application in light
      emission. More importantly, Ln(3+)@NENU-522 can emit white light by encapsulating
      different molar ratios of Eu(3+) and Tb(3+) ions. Additionally, Tb(3+)@NENU-522
      is found to be useful as a fluorescent indicator for the qualitative and
      quantitative detection of nitroaromatic explosives with different numbers of -NO2
      groups, and the concentrations of complete quenching are about 2000, 1000, and 80
      ppm for nitrobenzene, 1,3-dinitrobenzene, and 2,4,6-trinitrophenol, respectively.
      Meanwhile, Tb(3+)@NENU-522 displays high selectivity and recyclability in the
      detection of nitroaromatic explosives. 

PMID- 25768043
TI  - Reaction between CH3O2 and BrO radicals: a new source of upper troposphere lower
      stratosphere hydroxyl radicals.
AB  - Over the last two decades it has emerged that measured hydroxyl radical levels in
      the upper troposphere are often underestimated by models, leading to the
      assertion that there are missing sources. Here we report laboratory studies of
      the kinetics and products of the reaction between CH3O2 and BrO radicals that
      shows that this could be an important new source of hydroxyl radicals:BrO + CH3O2
      -> products (1). The temperature dependent value in Arrhenius form of k(T) is k1
      = (2.42-0.72+1.02) * 10-14 exp[(1617 +/- 94)/T] cm3 molecule-1 s-1. In addition,
      CH2OO and HOBr are believed to be the major products. Global model results
      suggest that the decomposition of H2COO to form OH could lead to an enhancement
      in OH of up to 20% in mid-latitudes in the upper troposphere and in the lower
      stratosphere enhancements in OH of 2-9% are inferred from model integrations. In
      addition, reaction 1 aids conversion of BrO to HOBr and slows polar ozone loss in
      the lower stratosphere.

PMID- 25768044
TI  - Whole left ventricular functional assessment from two minutes free breathing
      multi-slice CINE acquisition.
AB  - Two major challenges in cardiovascular MRI are long scan times due to slow MR
      acquisition and motion artefacts due to respiratory motion. Recently, a Motion
      Corrected-Compressed Sensing (MC-CS) technique has been proposed for free
      breathing 2D dynamic cardiac MRI that addresses these challenges by
      simultaneously accelerating MR acquisition and correcting for any arbitrary
      motion in a compressed sensing reconstruction. In this work, the MC-CS framework
      is combined with parallel imaging for further acceleration, and is termed Motion
      Corrected Sparse SENSE (MC-SS). Validation of the MC-SS framework is demonstrated
      in eight volunteers and three patients for left ventricular functional assessment
      and results are compared with the breath-hold acquisitions as reference. A non
      significant difference (P > 0.05) was observed in the volumetric functional
      measurements (end diastolic volume, end systolic volume, ejection fraction) and
      myocardial border sharpness values obtained with the proposed and gold standard
      methods. The proposed method achieves whole heart multi-slice coverage in 2 min
      under free breathing acquisition eliminating the time needed between breath-holds
      for instructions and recovery. This results in two-fold speed up of the total
      acquisition time in comparison to the breath-hold acquisition. 

PMID- 25768045
TI  - Supramolecular Polymers: Historical Development, Preparation, Characterization,
      and Functions.

PMID- 25768047
TI  - Correct positioning of central venous catheters using a new electric method.
AB  - PURPOSE: In order to find the correct final position of the tip of a central
      venous catheter, we have developed a new electric method (the Proximity of
      Cardiac Motion (PCM) method), designed to work in tandem with the existing ECG
      based method. METHODS: A small, patient-safe, high-frequency current is fed
      through the catheter (via the saline-filled lumen of the catheter, or a stylet).
      Simultaneously, the resulting voltage is measured by two electrodes on the
      frontal thoracic skin. The catheter tip hence functions as a current source
      inside the vasculature. The cardiac motion produces a variation in the amplitude
      of the measured voltage in the rhythm of the cardiac cycle, and the strength of
      this oscillatory variation is proportional to the strength of the incident
      current field on the heart, which is a rapidly decaying function of the distance
      between the catheter tip and the cavoatrial junction (CAJ). Hence the strength of
      this oscillatory variation is a strong indicator for the proximity of the
      catheter tip with respect to the CAJ. RESULTS: The new method has been tested in
      an animal model, yielding an average final position of the catheter tip of 2.1 cm
      above the CAJ, with a maximum deviation of 0.5 cm. CONCLUSIONS: We conclude that
      the new PCM method can be combined with the existing ECG method, and may
      potentially have significant added value when the ECG method cannot be applied,
      for example, in patients with atrial fibrillation or a pacemaker.

PMID- 25768046
TI  - Phage-display-guided nanocarrier targeting to atheroprone vasculature.
AB  - In regions of the circulation where vessels are straight and unbranched, blood
      flow is laminar and unidirectional. In contrast, at sites of curvature, branch
      points, and regions distal to stenoses, blood flow becomes disturbed.
      Atherosclerosis preferentially develops in these regions of disturbed blood flow.
      Current therapies for atherosclerosis are systemic and may not sufficiently
      target these atheroprone regions. In this study, we sought to leverage the
      alterations on the luminal surface of endothelial cells caused by this
      atheroprone flow for nanocarrier targeting. In vivo phage display was used to
      discover unique peptides that selectively bind to atheroprone regions in the
      mouse partial carotid artery ligation model. The peptide GSPREYTSYMPH (PREY) was
      found to bind 4.5-fold more avidly to the region of disturbed flow and was used
      to form targeted liposomes. When administered intravenously, PREY-targeted
      liposomes preferentially accumulated in endothelial cells in the partially
      occluded carotid artery and other areas of disturbed flow. Proteomic analysis and
      immunoblotting indicated that fibronectin and Filamin-A were preferentially bound
      by PREY nanocarriers in vessels with disturbed flow. In additional experiments,
      PREY nanocarriers were used therapeutically to deliver the nitric oxide synthase
      cofactor tetrahydrobiopterin (BH4), which we have previously shown to be
      deficient in regions of disturbed flow. This intervention increased vascular BH4
      and reduced vascular superoxide in the partially ligated artery in wild-type mice
      and reduced plaque burden in the partially ligated left carotid artery of fat fed
      atheroprone mice (ApoE(-/-)). Targeting atheroprone sites of the circulation with
      functionalized nanocarriers provides a promising approach for prevention of early
      atherosclerotic lesion formation. 

PMID- 25768048
TI  - Congenital anomalies of superior vena cava and their implications in central
      venous catheterization.
AB  - Congenital anomalies of superior vena cava (SVC) are generally discovered
      incidentally during central venous catheter (CVC) insertion, pacemaker electrode
      placement, and cardiopulmonary bypass surgery. Persistent left SVC (PLSVC) is a
      rare (0.3%) anomaly in healthy subjects, usually asymptomatic, but when present
      and undiagnosed, it may be associated with difficulties and complications of CVC
      placement. In individuals with congenital heart anomalies, its prevalence may be
      up to 10 times higher than in the general population.In this perspective,
      awareness of the importance of the incidental finding of PLSV during CVC
      placement is crucial. To improve knowledge of this rare but potentially dangerous
      condition, we describe the embryological origin of SVC, its normal anatomy, and
      possible congenital anomalies of the venous system and of the heart, including
      the presence of a right to left cardiac shunt. Diagnosis of PLSVC as well as the
      clinical complications and technical impact of SVC congenital anomalies for CVC
      placement are emphasized. 

PMID- 25768050
TI  - Pseudoendogenous origin of prednisolone in pigs from the food chain.
AB  - The debate about the origin of prednisolone in animal organisms has lasted for 5
      years. Bovine species have been the most studied, but studies on humans and
      horses are also present in the literature. Even if prednisolone in pigs does not
      yet represent a problem for control agencies, interest has recently increased
      with regard to this species. To date, there has been just a single study in the
      literature about this topic, performed on 10 sows treated with prednisolone or a
      synthetic analogue of adrenocorticotropic hormone. We therefore initiated a study
      on 80 pigs, a number considered representative in relation to the expected
      frequency (prevalence) of prednisolone detection in urine collected at slaughter.
      Prednisolone was detected in urine both at the farm and at the slaughterhouse,
      with a concentration and frequency higher at slaughter. The presence of
      prednisolone was also studied in the adrenal glands, where the corticosteroids
      are produced in response to stress, and it was detected in 89% of the samples.
      These results, together with the similar behaviours of prednisolone and cortisol,
      i.e. a mutual rise in the two corticosteroids in urine collected at the
      slaughterhouse and the correlation between the concentrations of the two
      corticosteroids in the adrenal glands, seem to indicate an endogenous origin of
      prednisolone in pigs.

PMID- 25768049
TI  - Insights into PBDE Uptake, Body Burden, and Elimination Gained from Australian
      Age-Concentration Trends Observed Shortly after Peak Exposure.
AB  - BACKGROUND: Population pharmacokinetic models combined with multiple sets of age
      concentration biomonitoring data facilitate back-calculation of chemical uptake
      rates from biomonitoring data. OBJECTIVES: We back-calculated uptake rates of
      PBDEs for the Australian population from multiple biomonitoring surveys (top
      down) and compared them with uptake rates calculated from dietary intake
      estimates of PBDEs and PBDE concentrations in dust (bottom-up). METHODS: Using
      three sets of PBDE elimination half-lives, we applied a population
      pharmacokinetic model to the PBDE biomonitoring data measured between 2002-2003
      and 2010-2011 to derive the top-down uptake rates of four key PBDE congeners and
      six age groups. For the bottom-up approach, we used PBDE concentrations measured
      around 2005. RESULTS: Top-down uptake rates of Sigma4BDE (the sum of BDEs 47, 99,
      100, and 153) varied from 7.9 to 19 ng/kg/day for toddlers and from 1.2 to 3.0
      ng/kg/day for adults; in most cases, they were--for all age groups--higher than
      the bottom-up uptake rates. The discrepancy was largest for toddlers with factors
      up to 7-15 depending on the congener. Despite different elimination half-lives of
      the four congeners, the age-concentration trends showed no increase in
      concentration with age and were similar for all congeners. CONCLUSIONS: In the
      bottom-up approach, PBDE uptake is underestimated; currently known pathways are
      not sufficient to explain measured PBDE concentrations, especially in young
      children. Although PBDE exposure of toddlers has declined in the past years, pre-
      and postnatal exposure to PBDEs has remained almost constant because the mothers'
      PBDE body burden has not yet decreased substantially.

PMID- 25768051
TI  - 13C isotopic fractionation during biodegradation of agricultural wastes.
AB  - Significant differences in delta(13)C signatures occur within and between plant
      tissues and their constituent biochemical entities, and also within and between
      heterotrophic bacteria and fungi and their metabolic products. Furthermore, (13)C
      isotopic fractionation occurs during the biodegradation of organic molecules as
      seen in the substrate, respired CO(2) and the microbial biomass, which could be
      related to substrate composition and/or microbial metabolism. The (13)C isotopic
      fractionation observed during the decomposition of a single defined C substrate
      appears to be due to the intra-molecular heterogeneity in (13)C in the substrate
      and to (13)C isotopic fractionation during microbial metabolism. Very limited
      data suggest that the latter may be quantitatively more important than the
      former. Studies with defined fungi in culture media have highlighted the
      complexities associated with the interpretation of the observed patterns of (13)C
      isotopic fractionation when a single defined C source is added to the culture
      medium which itself contains one or more C sources. Techniques involving (13)C
      enrichment or paired treatments involving an equivalent C(3)- and C(4)-derived
      substrate have been devised to overcome the problem of background C in the
      culture medium and (13)C isotopic fractionation during metabolism. Studies with
      complex substrates have shown an initial (13)C depletion phase in respired CO(2)
      followed by a (13)C enrichment phase which may or may not be followed by another
      (13)C depletion phase. Basic studies involving an integrated approach are
      required to gain a new insight into (13)C isotopic fractionation during organic
      residue decomposition, by simultaneous measurements of delta(13)C in all C
      moieties. New analytical tools to measure real-time changes in delta(13)CO(2) and
      the intra-molecular delta(13)C distribution within plant biochemical entities
      offer new opportunities for unravelling the complex interactions between
      substrate and microbial metabolism with respect to (13)C isotopic fractionation
      during biodegradation.

PMID- 25768052
TI  - Destination memory and cognitive theory of mind in normal ageing.
AB  - Destination memory is the ability to remember the destination to which a piece of
      information has been addressed (e.g., "Did I tell you about the promotion?").
      This ability is found to be impaired in normal ageing. Our work aimed to link
      this deterioration to the decline in theory of mind. Forty younger adults (M age
      = 23.13 years, SD = 4.00) and 36 older adults (M age = 69.53 years, SD = 8.93)
      performed a destination memory task. They also performed the False-belief test
      addressing cognitive theory of mind and the Reading the mind in the eyes test
      addressing affective theory of mind. Results showed significant deterioration in
      destination memory, cognitive theory of mind and affective theory of mind in the
      older adults. The older adults' performance on destination memory was
      significantly correlated with and predicted by their performance on cognitive
      theory of mind. Difficulties in the ability to interpret and predict others'
      mental states are related to destination memory decline in older adults. 

PMID- 25768053
TI  - Genetic characterization, nickel tolerance, biosorption, kinetics, and uptake
      mechanism of a bacterium isolated from electroplating industrial effluent.
AB  - Electroplating industries in Madurai city produce approximately 49,000 L of
      wastewater and 1200 L of sludge every day revealing 687-5569 ppm of nickel (Ni)
      with other contaminants. Seventeen Ni-tolerant bacterial strains were isolated
      from nutrient-enriched effluents. Among them one hyper Ni accumulating strain was
      scored and identified as Bacillus cereus VP17 on the basis of morphology,
      biochemical tests, 16S rDNA gene sequencing, and phylogenetic analysis.
      Equilibrium data of Ni(II) ions using the bacterium as sorbent at isothermal
      conditions (37  degrees C) and pH 6 were best adjusted by Langmuir (R(2) =
      0.6268) and Freundlich models (R(2) = 0.9505). Experimental validation reveals Ni
      sorption takes place on a heterogeneous surface of the biosorbent, and predicted
      metal sorption capacity is 434 ppm. The pseudo-second-order kinetic model fitted
      the biosorption kinetic data better than the pseudo-first-order kinetic model
      (R(2) = 0.9963 and 0.3625). Scanning electron microscopy, energy dispersive X
      ray, and Fourier transform infrared spectroscopy studies of the bacterial strain
      with and without Ni(II) ion reveals the biosorption mechanism. The results
      conclude possibilities of using B. cereus VP17 for Ni bioremediation.

PMID- 25768054
TI  - Detection of tissue edema in breast cancer-associated lymphedema.

PMID- 25768057
TI  - Unilateral sequential endoscopic thoracic sympathectomy for palmar hyperhidrosis:
      a proposed technique to overcome compensatory hyperhidrosis and improve plantar
      hyperhidrosis.
AB  - BACKGROUND: Although endoscopic thoracic sympathectomy (ETS) offers permanent
      cure of palmar hyperhidrosis (PH), compensatory hyperhidrosis (CH) often
      complicates the procedure. We analyzed the outcomes of a 2-month interval for
      unilateral sequential ETS (S-ETS) in comparison with simultaneous bilateral ETS
      (B-ETS), notably regarding CH and associated plantar hyperhidrosis, in treating
      patients with PH. PATIENTS AND METHODS: Four hundred seven patients with
      intractable PH were randomly assigned into two groups: the B-ETS group (204
      patients) and the S-ETS group (203 patients). RESULTS: Three hundred sixty-four
      patients completed the study. Complication rates were comparable for both groups.
      No patient died perioperatively, and no conversion was necessary. Treatment
      success on follow-up was 97.2% for S-ETS and 96.7% for B-ETS. The incidence of CH
      was decreased substantially from 131 (71.1%) patients in the B-ETS group to 22
      (12.2%) patients in the S-ETS group (P<.001), with no patient suffering severe CH
      in the S-ETS group compared with 33 (25.5%) patients in the B-ETS group. Eighty
      four (58.3%) patients in the S-ETS group had simultaneous disappearance or
      decreased perspiration on the soles. All patients in the S-ETS group were
      satisfied, whereas 37.9% of B-ETS patients were unsatisfied with their operation,
      mostly because of CH and recurrences. CONCLUSIONS: Although both sympathectomies
      were effective, safe, and minimally invasive methods for treatment of PH,
      unilateral sequential ETS appeared to be a more optimal technique in terms of
      reduction of CH to a minimum and improvement of associated plantar hyperhidrosis.

PMID- 25768058
TI  - Implementation of the Centers for Medicare & Medicaid Services' Nonpayment Policy
      for Preventable Hospital-Acquired Conditions in Rural and Nonrural US Hospitals.
AB  - Preventable adverse patient outcomes and hospital characteristics in rural versus
      nonrural US hospitals under the new Centers for Medicare & Medicaid Services
      reimbursement policy were examined using the American Hospital Association Annual
      Survey and Hospital Compare data. Under the new Centers for Medicare & Medicaid
      Services policy, rural hospitals tended to have fewer hospital-acquired
      conditions than nonrural hospitals except for patient falls. Case mix was
      consistently related to falls after controlling for hospital characteristics. 

PMID- 25768059
TI  - Impact of Magnet Culture in Maintaining Quality Outcomes During Periods of
      Organizational Transition.
AB  - Organizational transition presents substantial risk to maintaining quality
      outcomes. The leadership style and culture present during periods of change and
      transition empower the frontline staff to react quickly and identify
      opportunities. The culture of Magnet develops the skill set that enables staff to
      be leaders in problem solving and identifying creative care delivery approaches.
      Objectives of this study were to analyze the impact of organizational transition
      on patient and staff satisfaction, quality, and safety in a Magnet-designated
      hospital and determine key factors contributing to these outcomes. 

PMID- 25768060
TI  - Long-term disability associated with war-related experience among Vietnam
      veterans: retrospective cohort study.
AB  - BACKGROUND: Recent combat operations have involved large numbers of personnel.
      Long-term health effects of military deployment remain largely unknown.
      OBJECTIVES: To examine patterns and trends in long-term disability among combat
      veterans and to relate disability to aspects of wartime experience. PARTICIPANTS:
      A total of 60,228 Australian military personnel deployed between 1962 and 1975
      during the Vietnam War, and 82,877 military personnel who were not deployed
      overseas. OUTCOME MEASURES: Accepted physician-assessed disability claims were
      evaluated over follow-up periods up to 50 years after deployment, and compared
      with age-matched controls. Multivariable analysis was used to examine differences
      by service branch, rank, age, and deployment duration. RESULTS: The steepest rise
      in disability incidence was observed among Vietnam veterans starting in the
      1990s, around 20-30 years after deployment for most veterans. After 1994, when
      Statements of Principles were introduced to guide evaluation of disability
      claims, the hazard ratio for disability incidence was 1.53 (95% confidence
      interval, 1.32-1.77) compared with the prior period. By January 2011, after an
      average follow-up of 42.5 years, 69.7% (95% confidence interval, 69.4%-70.1%) of
      veterans had at least 1 war-related disability. Many veterans had multiple
      disabilities, with leading causes being eye and ear disorders (48.0%), mental
      health conditions (47.9%), and musculoskeletal disorders (18.4%). For specific
      categories of disability, relative risks for accepted claims among veterans
      compared with controls were highest for mental health disorders, at 22.9 (21.9
      24.0) and lowest for injuries, at 1.5 (1.4-1.6) with a relative risk for any
      disability of 3.7 (3.7-3.8). Veterans with service of >1 year were 2.5 (2.2-2.7)
      times more likely to have a mental health disability than those who served <100
      days, and 2.3 (2.1-2.5) times more likely to have other disabilities.
      CONCLUSIONS: Long-term effects of deployment into military conflicts are
      substantial, and likelihood of war-related disability is associated with service
      history. If similar patterns follow from more recent conflicts, significant
      additional resources will be needed to prevent and treat long-term health
      conditions among veterans.

PMID- 25768061
TI  - Implementation of an analytical model for leakage neutron equivalent dose in a
      proton radiotherapy planning system.
AB  - Equivalent dose from neutrons produced during proton radiotherapy increases the
      predicted risk of radiogenic late effects. However, out-of-field neutron dose is
      not taken into account by commercial proton radiotherapy treatment planning
      systems. The purpose of this study was to demonstrate the feasibility of
      implementing an analytical model to calculate leakage neutron equivalent dose in
      a treatment planning system. Passive scattering proton treatment plans were
      created for a water phantom and for a patient. For both the phantom and patient,
      the neutron equivalent doses were small but non-negligible and extended far
      beyond the therapeutic field. The time required for neutron equivalent dose
      calculation was 1.6 times longer than that required for proton dose calculation,
      with a total calculation time of less than 1 h on one processor for both
      treatment plans. Our results demonstrate that it is feasible to predict neutron
      equivalent dose distributions using an analytical dose algorithm for individual
      patients with irregular surfaces and internal tissue heterogeneities. Eventually,
      personalized estimates of neutron equivalent dose to organs far from the
      treatment field may guide clinicians to create treatment plans that reduce the
      risk of late effects. 

PMID- 25768062
TI  - Validation of the Andon KD-5851 upper arm blood pressure monitor, for self
      measurement according to the European Society of Hypertension International
      Protocol revision 2010.
AB  - OBJECTIVE: This study aimed to validate the Andon KD-5851 upper arm blood
      pressure (BP) monitor according to the European Society of Hypertension
      International Protocol (ESH-IP) revision 2010. METHODS: A total of 33 eligible
      participants were included in the study. Sequential measurements of BPs were
      performed using a mercury sphygmomanometer and the device, and the data analysis
      was carried out following precisely the ESH-IP revision 2010. RESULTS: The device
      had 82, 98, and 99 measurements within 5, 10, and 15 mmHg for systolic blood
      pressure and 85, 95, and 99 measurements for diastolic blood pressure,
      respectively. The average device-observer difference was -0.53+/-4.00 mmHg for
      systolic blood pressure and -1.15+/-4.06 mmHg for diastolic blood pressure. The
      device passed all the criteria according to the ESH-IP revision 2010. CONCLUSION:
      According to the validation results on the basis of the ESH-IP revision 2010, the
      Andon KD-5851 upper arm BP monitor can be recommended for self/home measurement
      in adults.

PMID- 25768063
TI  - Validation of the A&D BP UB-543 wrist device for home blood pressure measurement
      according to the European Society of Hypertension International Protocol revision
      2010.
AB  - The aim of this study was to determine the accuracy of the A&D BP UB-543 wrist
      device for home blood pressure (BP) measurement according to the International
      Protocol of the European Society of Hypertension. The A&D BP UB-543 monitor is
      provided with a correct position guidance (CPG) indicator that ensures the
      correct placement of the wrist at the heart level. Device evaluation was carried
      out in 33 patients with the CPG indicator on. The mean age of the patients was
      53.1+/-16.4 years, the mean systolic BP was 141.8+/-25.1 mmHg (range 84 : 196),
      the mean diastolic BP was 88.2+/-14.5 mmHg (range 34 : 132), the mean arm
      circumference was 29.0+/-3.6 cm (range 21 : 38), and the mean wrist circumference
      was 17.5+/-1.4 cm (range 15 : 20). The protocol requirements were followed
      precisely. The device passed all requirements, fulfilling the standards of the
      protocol. On average, the device overestimated the systolic BP by 1.1+/-2.9 mmHg
      and underestimated diastolic BP by 0.1+/-3.0 mmHg. These data show that the A&D
      BP UB-543 wrist device used correctly with the CPG indicator on met the
      requirements for validation by the International Protocol and can be recommended
      for clinical use in the adult population. 

PMID- 25768064
TI  - Impact of 24 Weeks of Resistance and Endurance Exercise on Glucose Tolerance in
      Persons with Multiple Sclerosis.
AB  - BACKGROUND: Recently, the authors reported an elevated prevalence of impaired
      glucose tolerance in individuals with multiple sclerosis (MS), compared with
      matched healthy controls, indicating metabolic defects that may increase
      comorbidity. MS also leads to a more inactive lifestyle, increasing the
      likelihood to develop fat accumulation, muscle wasting/weakness, and exercise
      intolerance. In other populations, these health complications can partly be
      reversed by physical exercise. OBJECTIVE: The aim of this study was to determine
      the impact of a mild-to-moderate-intensity exercise program on glucose tolerance,
      ranging between normal and impaired, in persons with MS. DESIGN: Persons with MS
      (mean expanded disability status scale, 3.3 +/- 0.2; mean age, 48 +/- 15 yrs)
      were randomized to an exercise group (n = 29) or a nonexercise control group (n =
      15). Glucose tolerance, as well as muscle strength, exercise tolerance, and body
      composition to validate the applied exercise program, was determined in both
      groups at baseline and after 6, 12, and 24 wks of mild-to-moderate-intensity
      combined endurance and resistance training. RESULTS: No effects on blood glucose
      and serum insulin were detected. However, 6 mos of exercise improved muscle
      strength, exercise tolerance, and lean tissue mass within the intervention group
      as compared with baseline. In the control group, no changes were detected.
      CONCLUSION: Twenty-four weeks of mild-to-moderate-intensity combined endurance
      and resistance training was not able to improve glycemic control in this cohort
      of persons with MS. Future research is warranted to investigate the influence of
      higher exercise intensities on glucose tolerance, in an attempt to remediate
      metabolic deficits and to decrease the prevalence of comorbidities in MS.

PMID- 25768065
TI  - Investigation of the Impact of Sports, Exercise, and Recreation Participation on
      Psychosocial Outcomes in a Population of Veterans with Disabilities: A Cross
      sectional Study.
AB  - OBJECTIVE: The aim of this study was to investigate possible effects that
      participation in sports, exercise, and recreation may have on self-esteem and
      quality-of-life in service members/veterans with disabilities. DESIGN: Two
      hundred twenty service members/veterans with disabilities who were participants
      in one of three annual adaptive sporting events took part in this cross-sectional
      study. Variables of interest were years of sport, exercise, and recreation
      participation since the onset of disability as well as the type of activity they
      engaged in. Main outcome measures were self-esteem and quality-of-life. RESULTS:
      A positive relationship was found between participant quality-of-life and the
      number of years spent participating in sports, exercise, and recreation since the
      onset of their disability. A significant difference was found between pre-event
      and postevent self-esteem scores. A significant difference was also found in self
      esteem scores between the levels of years of participation in sports, exercise,
      and recreation when averaged across activity type. Finally, there were
      significant differences found on self-esteem scores between the levels of type of
      activity averaged across years of participation. CONCLUSIONS: Our results
      indicate that participation in sports, exercise, and recreation has a positive
      influence on self-esteem and quality-of-life in individuals with disabilities.

PMID- 25768066
TI  - Upper esophageal sphincter opening during swallow in stroke survivors.
AB  - OBJECTIVE: Timely and efficient upper esophageal sphincter (UES) opening may be
      critical to safe transport of food or liquid to the stomach and to prevent
      aspiration during the swallow. The purpose of this study was to examine the
      temporal and biomechanical characteristics of the UES opening in stroke
      survivors. METHOD: Maximum duration and width of the UES opening were obtained
      from 15 stroke survivors with aspiration and 15 stroke survivors with no
      aspiration. The control group was composed of 15 normal subjects undergoing
      videofluoroscopic swallowing examinations. The videofluoroscopic swallowing
      examination protocol was as follows: two swallows of 5 ml thin liquid and two
      swallows of 10 ml thin liquid. Statistical comparisons were made by repeated
      measurements of analysis of variance, and the significance level was set at P <
      0.025. RESULT: The stroke survivors with aspiration, the stroke survivors without
      aspiration, and the control group differed significantly for duration of UES
      opening (P < 0.01) but not maximum width of UES opening. CONCLUSION: Prolonged
      UES opening may be related to prolonged pharyngeal transition of the bolus and
      slower UES muscle contraction and hyolaryngeal excursion after stroke.

PMID- 25768067
TI  - Benefits for Adults with Transfemoral Amputations and Peripheral Artery Disease
      Using Microprocessor Compared with Nonmicroprocessor Prosthetic Knees.
AB  - OBJECTIVE: Approximately 50% of people with leg amputation fall annually.
      Evidence suggests that microprocessor knees (MK) may decrease falls and improve
      prosthetic function in people with traumatic amputations. This study explored
      whether adults with transfemoral amputations and peripheral artery disease would
      have reduced falls and improved balance confidence, balance, and walking ability
      when using prostheses with MK compared with non-MK. DESIGN: This was a
      prospective cohort study. RESULTS: Eight subjects averaged 60.8 +/- 11.3 yrs or
      age and 9.5 +/- 16.1 yrs since first amputation. Four were K1-K2-level and four
      were K3-level functional walkers; only Houghton prosthetic use score was
      different between K1-K2 and K3 walkers (P = 0.03). After 48.3 +/- 38.1 wks of
      acclimation using MK, subjects demonstrated improvements in fear of falling,
      balance confidence, Timed Up-and-Go time, and rate of falls (P < 0.05). The
      improvements in fear of falling, balance confidence, and rate of falls had large
      effect sizes (d > 0.80). Average decreased Timed Up-and-Go time (12.3 secs) had a
      medium effect size (d = 0.34). Decreases in the number of falls correlated with
      faster Timed Up-and-Go speed (rho = -0.76) and greater balance confidence (rho =
      0.83). CONCLUSIONS: People with peripheral artery disease and transfemoral
      amputations had fewer falls and improved balance confidence and walking
      performance when using prostheses with MK.

PMID- 25768068
TI  - Intensive Gait Training for Older Adults with Symptomatic Knee Osteoarthritis.
AB  - OBJECTIVE: The objective of this study was to determine whether individualized
      gait training is more effective than usual care for reducing mobility disability
      and pain in individuals with symptomatic knee osteoarthritis. DESIGN: Adults aged
      60 yrs or older with symptomatic knee osteoarthritis and mobility limitations
      were randomized to physical therapist-directed gait training on an instrumented
      treadmill, with biofeedback individualized to optimize knee movements, biweekly
      for 3 mos or usual care (control). Mobility disability was defined using Late
      Life Function and Disability Index Basic Lower Limb Function score (primary);
      mobility limitations, using timed 400-m walk, chair-stand, and stair-climb tests;
      and symptoms, using the Knee Injury/Osteoarthritis Outcome Score at baseline, as
      well as at 3, 6, and 12 mos. The analyses used longitudinal mixed models.
      RESULTS: There were no significant intergroup differences between the 35 gait
      training (74.3% women; age, 69.7 +/- 8.2 yrs) and 21 control (57.1% women; age,
      68.9 +/- 6.5 yrs) participants at baseline. At 3 mos, the gait-training
      participants had greater improvement in mobility disability (4.3 +/- 1.7; P =
      0.0162) and symptoms (8.6 +/- 4.1; P = 0.0420). However, there were no intergroup
      differences detected for pain, 400-m walk, chair-stand, or stair-climb times at 3
      mos or for any outcomes at 6 or 12 mos. CONCLUSIONS: Compared with usual care,
      individualized gait training resulted in immediate improvements in mobility
      disability knee symptoms in adults with symptomatic knee osteoarthritis, but
      these effects were not sustained.

PMID- 25768070
TI  - Effectiveness of Ultrasound Guidance on Intraarticular and Periarticular Joint
      Injections: Systematic Review and Meta-analysis of Randomized Trials.
AB  - OBJECTIVE: The aim of this study was to evaluate the effectiveness and accuracy
      of ultrasound-guided intraarticular and periarticular joint injections as
      compared with landmark-guided injections technique. METHODS: A systematic
      literature search was performed in Medline, Web of Science, Embase, the Cochrane
      Central Register of Controlled Trials, reference lists of articles, and other
      sources. Only randomized controlled trials were included. Two reviewers
      independently selected and assessed each study for quality and extracted data.
      RESULTS: Twelve randomized controlled trials were included in the meta-analysis.
      The results indicated that ultrasound-guided intraarticular and periarticular
      joint injections were more accurate than the landmark-guided injections (odds
      ratio, 0.36; 95% confidence interval, 0.22-0.60). Ultrasound-guided joint
      injections significantly decreased the visual analog scale scores at both 2 wks
      (mean difference, -9.57; 95% confidence interval, -13.14 to -5.99) (P < 0.00001)
      and 6 wks (mean difference, -14.21; 95% confidence interval, -18.20 to -10.21) (P
      < 0.00001) after injection. There was no statistically significant difference in
      visual analog scale score at 12 wks between ultrasound-guided and landmark-guided
      intraarticular and periarticular joint injections (mean difference, -4.42; 95%
      confidence interval, -11.71 to 2.87) (P = 0.23). CONCLUSIONS: Intraarticular and
      periarticular injections using ultrasound guidance significantly improves the
      accuracy of joint injections, and there is a significant decrease in visual
      analog scale scores for up to 6 wks after injection. The effect of ultrasound
      guidance on the long-term outcome of joint injections is inconclusive. The
      improved accuracy of injections was associated with pain relief. The authors
      recommend routine ultrasound guidance for intraarticular and periarticular
      injections.

PMID- 25768069
TI  - Is Pain in One Knee Associated with Isometric Muscle Strength in the
      Contralateral Limb?: Data From the Osteoarthritis Initiative.
AB  - OBJECTIVE: Knee pain and muscle weakness confer risk for knee osteoarthritis
      incidence and progression. The purpose of this study was to determine whether
      unilateral knee pain influences contralateral thigh muscle strength. DESIGN: Of
      4796 Osteoarthritis Initiative participants, 224 (mean +/- SD age, 63.9 +/- 8.9
      yrs) cases could be matched to a control. Cases were defined as having unilateral
      knee pain (numerical rating scale, >= 4/10; >=infrequent pain) and one pain-free
      knee (numerical rating scale, 0-1; <=infrequent pain; Western Ontario and
      McMaster Universities Arthritis Index, <= 1). Controls were defined as having
      bilaterally pain-free knees (numerical rating scale, 0-1; <=infrequent pain;
      Western Ontario and McMaster Universities Arthritis Index, <= 1). Maximal
      isometric muscle strength (N) was compared between limbs in participants with
      unilateral pain (cases) as well as between pain-free limbs of cases and controls.
      RESULTS: Knee extensor/flexor strength in pain-free limbs of the cases was lower
      than that in bilaterally pain-free controls (-5.5%/-8.4%; P = 0.043/P = 0.022).
      Within the cases, maximum extensor/flexor strength was significantly lower in the
      painful limb than in the pain-free limb (-6.3%/4.1%; P < 0.0001/P = 0.015).
      CONCLUSIONS: These results suggest that strength in limbs without knee pain is
      associated with the pain status of the contralateral knee. The strength
      difference between unilateral pain-free cases and matched bilateral pain-free
      controls was similar to that between limbs in persons with unilateral knee pain.
      Lower strength caused by contralateral knee pain might be centrally mediated.

PMID- 25768071
TI  - Evidence for the Use of Ischemic Compression and Dry Needling in the Management
      of Trigger Points of the Upper Trapezius in Patients with Neck Pain: A Systematic
      Review.
AB  - The aim of this review was to describe the effects of ischemic compression and
      dry needling on trigger points in the upper trapezius muscle in patients with
      neck pain and compare these two interventions with other therapeutic
      interventions aiming to inactivate trigger points. Both PubMed and Web of Science
      were searched for randomized controlled trials using different key word
      combinations related to myofascial neck pain and therapeutic interventions. Four
      main outcome parameters were evaluated on short and medium term: pain, range of
      motion, functionality, and quality-of-life, including depression. Fifteen
      randomized controlled trials were included in this systematic review. There is
      moderate evidence for ischemic compression and strong evidence for dry needling
      to have a positive effect on pain intensity. This pain decrease is greater
      compared with active range of motion exercises (ischemic compression) and no or
      placebo intervention (ischemic compression and dry needling) but similar to other
      therapeutic approaches. There is moderate evidence that both ischemic compression
      and dry needling increase side-bending range of motion, with similar effects
      compared with lidocaine injection. There is weak evidence regarding its effects
      on functionality and quality-of-life. On the basis of this systematic review,
      ischemic compression and dry needling can both be recommended in the treatment of
      neck pain patients with trigger points in the upper trapezius muscle. Additional
      research with high-quality study designs are needed to develop more conclusive
      evidence. 

PMID- 25768072
TI  - Is There an Association Between Lumbosacral Radiculopathy and Painful Gluteal
      Trigger Points?: A Cross-sectional Study.
AB  - OBJECTIVE: The objective of this study was to compare the prevalence of gluteal
      trigger point in patients with lumbosacral radiculopathy with that in healthy
      volunteers. DESIGN: In a cross-sectional, multistage sampling method, patients
      with clinical, electromyographic, and magnetic resonance imaging findings
      consistent with lumbosacral radiculopathy were examined for the presence of
      gluteal trigger point. Age- and sex-matched clusters of healthy volunteers were
      selected as the control group. The primary outcome of the study was the presence
      or absence of gluteal trigger point in the gluteal region of the patients and the
      control group. RESULTS: Of 441 screened patients, 271 met all the inclusion
      criteria for lumbosacral radiculopathy and were included in the study. Gluteal
      trigger point was identified in 207 (76.4%) of the 271 patients with
      radiculopathy, compared with 3 (1.9%) of 152 healthy volunteers (P < 0.001). The
      location of gluteal trigger point matched the side of painful radiculopathy in
      74.6% of patients with a unilateral radicular pain. There was a significant
      correlation between the side of the gluteal trigger point and the side of
      patients' radicular pain (P < 0.001). CONCLUSIONS: Although rare in the healthy
      volunteers, most of the patients with lumbosacral radiculopathy had gluteal
      trigger point, located at the painful side. Further studies are required to test
      the hypothesis that specific gluteal trigger point therapy could be beneficial in
      these patients.

PMID- 25768073
TI  - Back pain in a middle-aged man: alkaptonuria.

PMID- 25768074
TI  - Rectus abdominis denervation after subcostal open laparotomy.

PMID- 25768075
TI  - Injury of the oculomotor nerve after aneurysmal subarachnoid hemorrhage:
      diffusion tensor tractography study.

PMID- 25768076
TI  - Sural Neuroma with Lumbosacral Radiculopathy-like Symptoms Diagnosed by
      Electrodiagnosis and Ultrasound.

PMID- 25768077
TI  - Dose delivered to the lumbosacral plexus from high-dose-rate brachytherapy for
      cervical cancer.
AB  - OBJECTIVE: To calculate dose delivered to the lumbosacral plexus (LSP) with
      cervical brachytherapy using 3-dimensional imaging, and to compare this with the
      position of the tandem in the pelvis using bony landmarks. We also report long
      term LSP toxicity outcomes. METHODS AND MATERIALS: Treatment planning images from
      55 patients treated with tandem and ring brachytherapy from October 2009 through
      November 2012 were reviewed. The LSP was contoured on planning computed
      tomographic scans to calculate dose received. Lumbosacral plexus dose was studied
      as a function of tandem distance from the sacrum and pubic symphysis (STratio)
      measured on digitally reconstructed radiographs. Patient and implant
      characteristics were included as covariates on LSP dose. Clinical follow up on
      LSP toxicity was recorded. RESULTS: Patients were prescribed 550 to 700 cGy using
      computed tomography-based imaged-guided brachytherapy for 4 to 5 fractions. The
      maximum dose to 2 cc (D2cc) of LSP ranged from 44 to 287 cGy per implant. The
      median D2cc was 118 cGy, corresponding to 18% of prescription dose. Patients with
      an STratio less than 0.33 (closer to the sacrum) and at least 0.33 had median LSP
      doses of 138 and 98 cGy, respectively. Lumbosacral plexus dose did not change
      significantly with body mass index, uterus position, or tumor stage. Two patients
      reported symptoms of peripheral neuropathy, with a median follow-up of 14.7
      months. CONCLUSIONS: The mean D2cc per fraction to the LSP is roughly 20% of the
      prescribed high dose-rate and varies with the position of the tandem from the
      sacrum. The dose threshold for radiation-induced neuropathy of the LSP remains
      undefined.

PMID- 25768078
TI  - The Use of Transvaginal Ultrasound in Type II Endometrial Cancer.
AB  - OBJECTIVE: To determine the use of the transvaginal ultrasound (TVUS) in
      postmenopausal women with type II endometrial cancer. METHODS/MATERIALS: A
      retrospective review was conducted for 173 women with pathology proven type II
      endometrial cancer at a single institution. Those who underwent preoperative TVUS
      were included, and the following data were obtained: endometrial stripe (EMS)
      measurement, uterine and/or adnexal findings, and uterine size/volume.
      Clinicopathologic factors were abstracted. Descriptive and regression analyses
      were performed. RESULTS: Fifty-eight women comprised the cohort, and the median
      age was 66.5 years (50-85 years). The most commonly reported symptom was
      postmenopausal bleeding in 53 patients (91.4%). The EMS was reported as thin (<=
      5 mm) or indistinct in 16 patients (27.5%). Approximately 60% of patients had 1
      or more ultrasound abnormalities: intracavitary mass (31%), intracavitary fluid
      (12.1%), myometrial lesion (31.03%), and adnexal mass (12.1%). Poorly
      differentiated endometrioid cancer (53.45%) represented the predominant
      histology. Of the 16 (27.5%) women with a thin/indistinct EMS, 5 women (8.6%) did
      not have any abnormal ultrasound findings whatsoever. CONCLUSIONS: Women with
      type II endometrial cancer had a thin/indistinct EMS on TVUS in approximately 25%
      of cases. Lack of any ultrasound abnormality, including a thickened EMS, was
      noted in approximately 10% of patients. The use of TVUS, which has been of value
      in type I cancer, is limited in type II endometrial cancer. Therefore,
      endometrial sampling should be included in the evaluation of all women with
      postmenopausal bleeding, regardless of EMS thickness.

PMID- 25768080
TI  - Strong correlation between molecular changes in endometrial carcinomas and
      concomitant hyperplasia.
AB  - OBJECTIVE: Endometrial cancer (EC) results from the accumulation of numerous
      genetic abnormalities contributing to the progression from hyperplasia to EC.
      Information on these various genetic changes has been primarily derived from
      studying groups of either hyperplasias or cancers.We evaluated both hyperplastic
      and EC tissue obtained from the same surgical specimens for KRAS mutations,
      microsatellite instability (MSI), and mismatch repair gene methylation, and
      results were correlated between the paired hyperplastic tissue and EC. The aim
      was to determine if molecular alterations appearing in ECs might also be present
      in the premalignant (hyperplastic) region of the tumor. METHODS: One hundred
      ninety-seven cases of EC with associated hyperplasia were evaluated. DNA samples
      were studied using primer sets for KRAS gene codons 12/13 and for MSI utilizing
      the Bethesda panel. Methylation testing was performed on specimens that were
      microsatellite unstable using the MRC Holland SALSA MS-MLPA methylation-specific
      DNA detection kit. RESULTS: Forty-one (20.8%) of 197 cancers demonstrated a KRAS
      mutation, with 35 (85.4%) of 41 accompanying hyperplasias also containing a KRAS
      mutation. Forty-five cancers (22.8%) were microsatellite unstable, with 38
      (84.4%) of 45 accompanying hyperplasias also demonstrating instability. Of the 45
      microsatellite unstable cancers, 28 (62.2%) demonstrated methylation in both the
      cancer and the accompanying hyperplasia, whereas 9 pairs (20%) showed no
      methylation for either the cancer or hyperplasia. CONCLUSIONS: Approximately 95%
      of endometrial specimens demonstrated identical molecular findings regarding KRAS
      mutation and microsatellite stability in the paired cancer and hyperplastic
      tissue. The same methylation pattern was found in 82.2% of the studied paired
      samples. Our findings strongly suggest that the molecular changes of KRAS
      mutation, MSI, and methylation occur early in the neoplastic process. We propose
      that endometrial biopsies revealing only hyperplasia should be studied for these
      molecular alterations as an indicator of possible early carcinogenesis.

PMID- 25768079
TI  - Sentinel Lymph Node Biopsy in Vulvar Cancer Using Combined Radioactive and
      Fluorescence Guidance.
AB  - OBJECTIVE: Near-infrared (NIR) fluorescence imaging using indocyanine green (ICG)
      has recently been introduced to improve the sentinel lymph node (SLN) procedure.
      Several optical tracers have been successfully tested. However, the optimal
      tracer formulation is still unknown. This study evaluates the performance of ICG
      technetium-99m (99mTc)-nanocolloid in relation to 2 most commonly used ICG-based
      formulas during SLN biopsy in vulvar cancer. METHODS AND MATERIALS: Twelve women
      who planned to undergo SLN biopsy for stage I vulvar cancer were prospectively
      included. Sentinel lymph node mapping was performed using the dual-modality
      radioactive and NIR fluorescence tracer ICG-99mTc-nanocolloid. All patients
      underwent combined SLN localization using NIR fluorescence and the (current) gold
      standard using blue dye and radioactive guidance. RESULTS: In all 12 patients, at
      least 1 SLN was detected during surgery. A total of 21 lymph nodes (median 2;
      range, 1-3) were resected. Median time between skin incision and first SLN
      detection was 8 (range, 1-22) minutes. All resected SLNs were both radioactive
      and fluorescent, although only 13 (62%) of 21 SLNs stained blue. Median
      brightness of exposed SLNs, expressed as signal-to-background ratio, was 5.4
      (range, 1.8-11.8). Lymph node metastases were found in 3 patients. CONCLUSIONS:
      Near-infrared fluorescence-guided SLN mapping is feasible and outperforms blue
      dye staining. Premixing ICG with 99mTc-nanocolloid provides real-time
      intraoperative imaging of the SN and seems to be the optimal tracer combination
      in terms of intraoperative detection rate of the SN (100%). Moreover, ICG-99mTc
      nanocolloid allows the administration of a 5-times lower injected dose of ICG
      (compared with ICG and ICG absorbed to human serum albumin) and can be injected
      up to 20 hours before surgery.

PMID- 25768081
TI  - Prognostic factors for ovarian epithelial cancer in the elderly: a case-control
      study.
AB  - OBJECTIVES: Ovarian cancer is the leading cause of mortality by gynecologic
      cancers in Western countries. Many publications have suggested that age may be an
      independent prognostic factor in ovarian carcinoma. There are only few data
      concerning the impact of treatments and geriatric features within the elderly
      population. METHODS/MATERIALS: We collected data of older (>= 70 years old)
      patients treated in our institution for an invasive ovarian carcinoma between
      1995 and 2011. First we described usual clinical and pathological features for
      these patients, as well as their outcome. We compared these parameters with that
      of young (<70 years old) patients treated during the same period. We then
      observed geriatric features in our set: Eastern Cooperative Oncology Group
      performance status, number of medications, Charlson index, body mass index,
      hemoglobin, and glomerular filtration rate. We finally looked for prognostic
      factors specific of the elderly population. RESULTS: One hundred nine elderly
      patients were identified and compared with 488 younger cases. There was no
      difference concerning clinicopathologic data. Surgery was more frequently
      complete in young women (58% vs 41.7%), and older patients received less
      chemotherapy courses and less taxanes (38.4% vs 67.1%). Young patients had a
      longer overall survival (median, 65.2 vs 26.2 months, P = 8.5E-10, log-rank
      test). Multivariate analyses confirmed that age was an independent prognostic
      factor and that within the elderly set the International Federation of Gynecology
      and Obstetrics stage, surgery results, number of chemotherapy cycles administered
      and performance status had a significant prognostic value. No clear correlation
      could be observed between geriatric characteristics and treatments
      administration. CONCLUSIONS: Ovarian cancer prognosis is poorer for older women,
      but they are more frequently suboptimally treated. No correlation could be
      observed between geriatric factors and surgery or chemotherapy achievement.
      Treatment decision should be based on objective geriatric assessment in order to
      improve outcome in this population.

PMID- 25768082
TI  - Schizophrenia: when clozapine fails.
AB  - PURPOSE OF REVIEW: This article reviews the recent evidence for therapeutic
      strategies for patients with treatment-resistant schizophrenia (TRS) not
      responding to or only partially responding to clozapine. RECENT FINDINGS: A
      number of pharmacological and nonpharmacological biological approaches for
      clozapine-resistant TRS have been evaluated in clinical trials. Among these, the
      evidence supporting clozapine augmentation by pharmacological approaches is weak
      and the reported benefits were modest at best. However, the results of a recent
      randomized trial suggest that electroconvulsive therapy (ECT) may be efficacious
      for the short-term treatment of patients with clozapine-resistant TRS. SUMMARY:
      There is currently insufficient evidence for efficacy of pharmacological
      augmentation strategies to clozapine. ECT may be a promising option, but further
      research is necessary to confirm its long-term effects. Moreover, further
      controlled studies are warranted to clarify the potential of other biological and
      psychosocial approaches to serve as adjuvant treatments in patients with
      clozapine-resistant TRS.

PMID- 25768083
TI  - Transcranial magnetic stimulation, transcranial direct current stimulation and
      electroconvulsive therapy for medication-resistant psychosis of schizophrenia.
AB  - PURPOSE OF REVIEW: Despite adequate antipsychotic treatment, 20-30% of patients
      with schizophrenia fail to obtain remission from psychosis. Physical stimulation
      treatments may provide an alternative therapy. In this review, we summarize the
      most recent studies regarding repetitive transcranial magnetic stimulation
      (rTMS), transcranial direct current stimulation (tDCS) and electroconvulsive
      therapy (ECT) for medication-resistant psychosis in schizophrenia. RECENT
      FINDINGS: Stimulation techniques in the treatment of medication-resistant
      psychosis have shown inconsistent results. Initial results of rTMS for auditory
      verbal hallucinations (AVH) were promising, but three recent large randomized
      controlled trials (RCTs) show similar results of rTMS as placebo. tDCS has shown
      initial promise as a treatment for AVH, but only in case studies and in two small
      RCTs. Larger studies are needed to define its efficacy. Although psychotic
      symptoms generally decrease after ECT, its efficacy has not been demonstrated in
      comparison with placebo. SUMMARY: Although previous meta-analyses indicate
      significant mean effect sizes for rTMS for intractable AVH, three recent large
      RCTs indicate no effect compared with placebo. The use of tDCS for resistant AVH
      and ECT for intractable psychosis has shown some initial promise, but adequately
      sized placebo-controlled RCTs are now needed. Taken together, the evidence for
      physical stimulation techniques to relieve medication-resistant psychosis is
      currently weak.

PMID- 25768084
TI  - Schizophrenia and psychoneuroimmunology: an integrative view.
AB  - PURPOSE OF REVIEW: Since decades immunological aberrancies have been reported in
      schizophrenia patients. As schizophrenia represents a heterogenous disorder with
      a variety of clinical manifestations, complex interactions between the immune
      system in the brain might have important etiological implications. RECENT
      FINDINGS: Recent findings of altered expression of immune-related genes, changes
      of peripheral and central cytokines, antibodies and immune cells point toward
      dysbalanced immune response processes in schizophrenia. SUMMARY: Based on
      immunogenetic factors, immune dysfunctions caused by infections, increased
      autoimmune reactivity and low-grade inflammatory processes in the periphery as
      well as in central nervous system may affect neurobiological circuits including
      changed neurotransmitter metabolisms contributing to pathophysiological
      alterations in schizophrenia. These immunological abnormalities might provide
      tools for better diagnostic characterization of this heterogenous disease and on
      the other side, they may also support the development of immune-related
      therapeutic strategies.

PMID- 25768085
TI  - Social impairment in schizophrenia: new approaches for treating a persistent
      problem.
AB  - PURPOSE OF REVIEW: Deficits in social cognition are an important determinant of
      social functioning in schizophrenia, a core feature of the illness that persists
      despite treatment. Recent research in neuroplasticity-based therapeutics shows
      that neural systems supporting core cognitive skills improve after targeted
      cognitive training, suggesting that social cognition, and concomitant social
      functioning, may be improved by targeting the neural systems supporting social
      cognition. However, the success of this approach depends on the extent to which
      the social brain is malleable. We review the neural effects of training programs
      focused on improving social cognition in healthy, schizophrenia, and other
      clinical samples. RECENT FINDINGS: The current literature suggests that the
      neural mechanisms underlying social cognition show neuroplastic changes after
      behavioral training and these neural changes confer concomitant benefits to
      social cognition and social behavior. Most research in schizophrenia has focused
      on emotion recognition, and although emotion recognition training has behavioral
      and neural benefits for schizophrenia, more advanced social cognitive processes
      need to be examined. SUMMARY: The data suggest that targeting neural systems
      underlying social cognition through socially focused behavioral interventions may
      improve social functioning impairments in schizophrenia. Questions remain
      regarding how to optimize training, which should be addressed in future work.

PMID- 25768086
TI  - Connectome and schizophrenia.
AB  - PURPOSE OF REVIEW: The neural connections, interconnections and organized
      networks of the central nervous system (CNS), which represent the human
      connectome, are critical for intact brain function. Consequently, disturbances at
      any level or juncture of these networks may alter behaviour and/or lead to brain
      dysfunction. In this review, we focus on highlighting recent work using advanced
      imaging methods to address alterations in the structural and functional
      connectome in patients with schizophrenia. RECENT FINDINGS: Using structural,
      diffusion, resting-state and task-related functional imaging and advanced
      computational analysis methods such as graph theory, more than 200 publications
      have addressed different aspects of structural and/or functional connectivity in
      schizophrenia over the last year. These studies have focused on determining how
      brain networks differ from those in controls, interact with symptom profiles
      within and across diagnoses, interface with disease-related cognitive impairments
      and confer genetic risk for the disorder. SUMMARY: Much existing evidence
      supports the view that schizophrenia is a disorder of altered brain connectivity.
      Recent and continued characterization of the structural and functional connectome
      in schizophrenia patients have advanced our understanding of the neurobiology
      underlying clinical symptoms and cognitive impairments in a particular patient,
      their overlaps with other neuropsychiatric disorders sharing common features as
      well as the contributions of genetic risk factors. Although the clinical utility
      of the schizophrenia connectome remains to be realized, recent findings provide
      further promise that research in this area may lead to improved diagnosis,
      treatments and clinical outcomes.

PMID- 25768087
TI  - An ADAM33 polymorphism associates with progression of preschool wheeze into
      childhood asthma: a prospective case-control study with replication in a birth
      cohort study.
AB  - BACKGROUND: The influence of asthma candidate genes on the development from
      wheeze to asthma in young children still needs to be defined. OBJECTIVE: To link
      genetic variants in asthma candidate genes to progression of wheeze to persistent
      wheeze into childhood asthma. MATERIALS AND METHODS: In a prospective study,
      children with recurrent wheeze from the ADEM (Asthma DEtection and Monitoring)
      study were followed until the age of six. At that age a classification (transient
      wheeze or asthma) was based on symptoms, lung function and medication use. In 198
      children the relationship between this classification and 30 polymorphisms in 16
      asthma candidate genes was assessed by logistic regression. In case of an
      association based on a p<0.10, replication analysis was performed in an
      independent birth cohort study (KOALA study, n = 248 included for the present
      analysis). RESULTS: In the ADEM study, the minor alleles of ADAM33 rs511898 and
      rs528557 and the ORMDL3/GSDMB rs7216389 polymorphisms were negatively associated,
      whereas the minor alleles of IL4 rs2243250 and rs2070874 polymorphisms were
      positively associated with childhood asthma. When replicated in the KOALA study,
      ADAM33 rs528557 showed a negative association of the CG/GG-genotype with
      progression of recurrent wheeze into childhood asthma (0.50 (0.26-0.97) p = 0.04)
      and no association with preschool wheeze. CONCLUSION: Polymorphisms in ADAM33,
      ORMDL3/GSDMB and IL4 were associated with childhood asthma in a group of children
      with recurrent wheeze. The replication of the negative association of the CG/GG
      genotype of rs528557 ADAM33 with childhood asthma in an independent birth cohort
      study confirms that a compromised ADAM33 gene may be implicated in the
      progression of wheeze into childhood asthma.

PMID- 25768088
TI  - Cartilage conduction is characterized by vibrations of the cartilaginous portion
      of the ear canal.
AB  - Cartilage conduction (CC) is a new form of sound transmission which is induced by
      a transducer being placed on the aural cartilage. Although the conventional forms
      of sound transmission to the cochlea are classified into air or bone conduction
      (AC or BC), previous study demonstrates that CC is not classified into AC or BC
      (Laryngoscope 124: 1214-1219). Next interesting issue is whether CC is a hybrid
      of AC and BC. Seven volunteers with normal hearing participated in this
      experiment. The threshold-shifts by water injection in the ear canal were
      measured. AC, BC, and CC thresholds at 0.5-4 kHz were measured in the 0%-, 40%-,
      and 80%-water injection conditions. In addition, CC thresholds were also measured
      for the 20%-, 60%-, 100%-, and overflowing-water injection conditions. The
      contributions of the vibrations of the cartilaginous portion were evaluated by
      the threshold-shifts. For AC and BC, the threshold-shifts by the water injection
      were 22.6-53.3 dB and within 14.9 dB at the frequency of 0.5-4 kHz, respectively.
      For CC, when the water was filled within the bony portion, the thresholds were
      elevated to the same degree as AC. When the water was additionally injected to
      reach the cartilaginous portion, the thresholds at 0.5 and 1 kHz dramatically
      decreased by 27.4 and 27.5 dB, respectively. In addition, despite blocking AC by
      the injected water, the CC thresholds in force level were remarkably lower than
      those for BC. The vibration of the cartilaginous portion contributes to the sound
      transmission, particularly in the low frequency range. Although the airborne
      sound is radiated into the ear canal in both BC and CC, the mechanism underlying
      its generation is different between them. CC generates airborne sound in the
      canal more efficiently than BC. The current findings suggest that CC is not a
      hybrid of AC and BC. 

PMID- 25768089
TI  - Fibroblast growth factor-9 enhances M2 macrophage differentiation and attenuates
      adverse cardiac remodeling in the infarcted diabetic heart.
AB  - Inflammation has been implicated as a perpetrator of diabetes and its associated
      complications. Monocytes, key mediators of inflammation, differentiate into pro
      inflammatory M1 macrophages and anti-inflammatory M2 macrophages upon
      infiltration of damaged tissue. However, the inflammatory cell types, which
      propagate diabetes progression and consequential adverse disorders, remain
      unclear. The current study was undertaken to assess monocyte infiltration and the
      role of fibroblast growth factor-9 (FGF-9) on monocyte to macrophage
      differentiation and cardioprotection in the diabetic infarcted heart. Db/db
      diabetic mice were assigned to sham, myocardial infarction (MI), and MI+FGF-9
      groups. MI was induced by permanent coronary artery ligation and animals were
      subjected to 2D transthoracic echocardiography two weeks post-surgery.
      Immunohistochemical and immunoassay results from heart samples collected suggest
      significantly increased infiltration of monocytes (Mean +/- SEM; MI: 2.02% +/-
      0.23% vs. Sham 0.75% +/- 0.07%; p<0.05) and associated pro-inflammatory cytokines
      (TNF-alpha, MCP-1, and IL-6), adverse cardiac remodeling (Mean +/- SEM; MI: 33%
      +/- 3.04% vs. Sham 2.2% +/- 0.33%; p<0.05), and left ventricular dysfunction
      (Mean +/- SEM; MI: 35.4% +/- 1.25% vs. Sham 49.19% +/- 1.07%; p<0.05) in the MI
      group. Importantly, treatment of diabetic infarcted myocardium with FGF-9
      resulted in significantly decreased monocyte infiltration (Mean +/- SEM; MI+FGF
      9: 1.39% +/- 0.1% vs. MI: 2.02% +/- 0.23%; p<0.05), increased M2 macrophage
      differentiation (Mean +/- SEM; MI+FGF-9: 4.82% +/- 0.86% vs. MI: 0.85% +/- 0.3%;
      p<0.05) and associated anti-inflammatory cytokines (IL-10 and IL-1RA), reduced
      adverse remodeling (Mean +/- SEM; MI+FGF-9: 11.59% +/- 1.2% vs. MI: 33% +/-
      3.04%; p<0.05), and improved cardiac function (Fractional shortening, Mean +/-
      SEM; MI+FGF-9: 41.51% +/- 1.68% vs. MI: 35.4% +/- 1.25%; p<0.05). In conclusion,
      our data suggest FGF-9 possesses novel therapeutic potential in its ability to
      mediate monocyte to M2 differentiation and confer cardiac protection in the post
      MI diabetic heart. 

PMID- 25768090
TI  - Head and neck mycetoma: the mycetoma research centre experience.
AB  - Mycetoma is a unique neglected tropical disease which is endemic in what is known
      as the "mycetoma belt". The disease has many devastating impacts on patients and
      communities in endemic area and is characterised by massive deformity,
      destruction and disability. Mycetoma is commonly seen in the foot and hand and
      less frequent in other parts of the body. Mycetoma of the head and neck is a
      rarity and is associated with high morbidity and even mortality if not treated
      early. In this communication we report on 49 patients with head and neck mycetoma
      followed up at the Mycetoma Research Centre in Khartoum. Most of the reported
      patients had actinomycetoma and the majority were young adult males from mycetoma
      endemic areas in the Sudan. Most of them were students, farmers and workers.
      Prior to presentation the majority had long disease duration and the cause was
      multifactorial. Advanced disease with massive lesion, deformity and disability
      was the common presentation. There was no obvious history of local trauma,
      familial tendency or other predisposing factor identified in this group of
      patients. MRI and CT scan were the most accurate diagnostic tools to determine
      the disease extent. The treatment outcome was rather poor and characterised by
      low cure rate, poor outcome and high follows-up dropout. Such a gloomy outcome
      calls for structured and objective health education programs. 

PMID- 25768091
TI  - In silico screening, genotyping, molecular dynamics simulation and activity
      studies of SNPs in pyruvate kinase M2.
AB  - Role of, 29-non-synonymous, 15-intronic, 3-close to UTR, single nucleotide
      polymorphisms (SNPs) and 2 mutations of Human Pyruvate Kinase (PK) M2 were
      investigated by in-silico and in-vitro functional studies. Prediction of
      deleterious substitutions based on sequence homology and structure based servers,
      SIFT, PANTHER, SNPs&GO, PhD-SNP, SNAP and PolyPhen, depicted that 19% emerged
      common between all the mentioned programs. SNPeffect and HOPE showed three
      substitutions (C31F, Q310P and S437Y) in-silico as deleterious and functionally
      important. In-vitro activity assays showed C31F and S437Y variants of PKM2 with
      reduced activity, while Q310P variant was catalytically inactive. The allosteric
      activation due to binding of fructose 1-6 bisphosphate (FBP) was compromised in
      case of S437Y nsSNP variant protein. This was corroborated through molecular
      dynamics (MD) simulation study, which was also carried out in other two variant
      proteins. The 5 intronic SNPs of PKM2, associated with sporadic breast cancer in
      a case-control study, when subjected to different computational analyses,
      indicated that 3 SNPs (rs2856929, rs8192381 and rs8192431) could generate an
      alternative transcript by influencing splicing factor binding to PKM2. We propose
      that these, potentially functional and important variations, both within exons
      and introns, could have a bearing on cancer metabolism, since PKM2 has been
      implicated in cancer in the recent past. 

PMID- 25768092
TI  - [Combination of Excessive Weight Gain and Interleukin-8: A Possible Predictor of
      Necrotising Enterocolitis in Neonates?].
AB  - BACKGROUND: Weight gain before the clinical diagnosis of necrotising
      enterocolitis (NEC) is described as a predictive factor. HYPOTHESIS: Weight gain
      of more than 5% one day prior to clinical suspicion plus increase of plasma
      Iinterleukin-8 (IL-8) are predictive for NEC. METHODS: 48 infants with diagnosis
      of NEC stage II and III were enrolled in a case-control study. Oral and
      parenteral nutrition, diuresis and kinetics of weight and of IL-8 were
      documented. RESULTS: 31 infants with NEC-II and 17 infants with NEC-III were
      enrolled. Weight gain>5% occurred in 35.3% of NEC-III, in 0% of NEC-II and in
      4.2% of the control group. IL-8 increased significantly [NEC-III (6 561.4 pg/mL)
      vs. NEC-II: (326.7 pg/mL) vs. control group (38.9 pg/mL); p<0.05]. Sensitivity of
      IL-8 in NEC-II was 87.10% (70.15-96.25) and in NEC-III 100.00% (80.33-100.00).
      Sensitivity of weight gain was 0.00% (0.00-11.32) in NEC-II and 35.29% (14.30
      61.65) in NEC-III. CONCLUSION: Weight gain>5% was found in only 35.3% of the
      cases with NEC-III. Combination of weight gain and IL-8 did not improve the
      diagnosis of NEC.

PMID- 25768093
TI  - [Foetal Mortality in Singleton Foetuses at and beyond Term - An Analysis of
      German Perinatal Data 2004-2013].
AB  - BACKGROUND: Foetal mortality appears to increase in postmature pregnancies. There
      is debate on the optimal timing of induction of labour vs. watchful waiting. The
      literature on retrospective analyses of secondary data is inconclusive. Different
      approaches to calculate foetal risk exist. Recent and relevant data are needed in
      order to realise an appropriate discussion. MATERIAL AND METHODS: Mortality in
      singleton foetuses in Germany, between 2004 and 2013 was analysed in relation to
      gestational age. Risk for foetal death is described comparing stillbirths per
      1,000 births at a particular gestational age (GA) vs. stillbirths per 1,000
      ongoing pregnancies ("fetus-at-risk" model). Access to German routine perinatal
      data was granted. We included all stillbirths in singleton foetuses with no
      malformations after 36+6 weeks gestational age from 2004 until 2013. RESULTS:
      5,933,117 births fulfilled our inclusion criteria. Foetal mortality per 1,000
      births during that week of pregnancy is lowest between 41+0 and 41+6 days of
      (0.7/1,000). Mortality then increases to 2.3/1,000 in 42+0 to 42+6 GA. With the
      "fetus-at-risk" model, mortality is low between 37+0 and 39+6 GA, ranging from
      0.2/1,000 ongoing pregnancies, increasing to 0.6/1,000 between 41+0 and 41+6, and
      2.3/1,000 in the following week. For pregnancies lasting longer than 42+6 weeks,
      the stillbirth risk is identical at 6.3/1,000 with both calculation methods.
      CONCLUSION: Fetal mortality is low until 41+6 weeks of pregnancy. Interpretation
      of current data does not support a policy of routine IOL before this gestational
      age in singleton foetuses.

PMID- 25768095
TI  - Defining robustness protocols: a method to include and evaluate robustness in
      clinical plans.
AB  - We aim to define a site-specific robustness protocol to be used during the
      clinical plan evaluation process. Plan robustness of 16 skull base IMPT plans to
      systematic range and random set-up errors have been retrospectively and
      systematically analysed. This was determined by calculating the error-bar dose
      distribution (ebDD) for all the plans and by defining some metrics used to define
      protocols aiding the plan assessment. Additionally, an example of how to
      clinically use the defined robustness database is given whereby a plan with sub
      optimal brainstem robustness was identified. The advantage of using different
      beam arrangements to improve the plan robustness was analysed. Using the ebDD it
      was found range errors had a smaller effect on dose distribution than the
      corresponding set-up error in a single fraction, and that organs at risk were
      most robust to the range errors, whereas the target was more robust to set-up
      errors. A database was created to aid planners in terms of plan robustness aims
      in these volumes. This resulted in the definition of site-specific robustness
      protocols. The use of robustness constraints allowed for the identification of a
      specific patient that may have benefited from a treatment of greater
      individuality. A new beam arrangement showed to be preferential when balancing
      conformality and robustness for this case. The ebDD and error-bar volume
      histogram proved effective in analysing plan robustness. The process of
      retrospective analysis could be used to establish site-specific robustness
      planning protocols in proton therapy. These protocols allow the planner to
      determine plans that, although delivering a dosimetrically adequate dose
      distribution, have resulted in sub-optimal robustness to these uncertainties. For
      these cases the use of different beam start conditions may improve the plan
      robustness to set-up and range uncertainties. 

PMID- 25768094
TI  - A hybrid computational method for the discovery of novel reproduction-related
      genes.
AB  - Uncovering the molecular mechanisms underlying reproduction is of great
      importance to infertility treatment and to the generation of healthy offspring.
      In this study, we discovered novel reproduction-related genes with a hybrid
      computational method, integrating three different types of method, which offered
      new clues for further reproduction research. This method was first executed on a
      weighted graph, constructed based on known protein-protein interactions, to
      search the shortest paths connecting any two known reproduction-related genes.
      Genes occurring in these paths were deemed to have a special relationship with
      reproduction. These newly discovered genes were filtered with a randomization
      test. Then, the remaining genes were further selected according to their
      associations with known reproduction-related genes measured by protein-protein
      interaction score and alignment score obtained by BLAST. The in-depth analysis of
      the high confidence novel reproduction genes revealed hidden mechanisms of
      reproduction and provided guidelines for further experimental validations. 

PMID- 25768096
TI  - Discriminatory components retracing strategy for monitoring the preparation
      procedure of Chinese patent medicines by fingerprint and chemometric analysis.
AB  - Chinese patent medicines (CPM), generally prepared from several traditional
      Chinese medicines (TCMs) in accordance with specific process, are the typical
      delivery form of TCMs in Asia. To date, quality control of CPMs has typically
      focused on the evaluation of the final products using fingerprint technique and
      multi-components quantification, but rarely on monitoring the whole preparation
      process, which was considered to be more important to ensure the quality of CPMs.
      In this study, a novel and effective strategy labeling "retracing" way based on
      HPLC fingerprint and chemometric analysis was proposed with Shenkang injection
      (SKI) serving as an example to achieve the quality control of the whole
      preparation process. The chemical fingerprints were established initially and
      then analyzed by similarity, principal component analysis (PCA) and partial least
      squares-discriminant analysis (PLS-DA) to evaluate the quality and to explore
      discriminatory components. As a result, the holistic inconsistencies of ninety
      three batches of SKIs were identified and five discriminatory components
      including emodic acid, gallic acid, caffeic acid, chrysophanol-O-glucoside, and p
      coumaroyl-O-galloyl-glucose were labeled as the representative targets to explain
      the retracing strategy. Through analysis of the targets variation in the
      corresponding semi-products (ninety-three batches), intermediates (thirty-three
      batches), and the raw materials, successively, the origins of the discriminatory
      components were determined and some crucial influencing factors were proposed
      including the raw materials, the coextraction temperature, the sterilizing
      conditions, and so on. Meanwhile, a reference fingerprint was established and
      subsequently applied to the guidance of manufacturing. It was suggested that the
      production process should be standardized by taking the concentration of the
      discriminatory components as the diagnostic marker to ensure the stable and
      consistent quality for multi-batches of products. It is believed that the
      effective and practical strategy would play a critical role in the guidance of
      manufacturing and help improve the safety of the final products. 

PMID- 25768098
TI  - Preoperative statins and outcomes after cardiac surgery: do not throw out the
      baby with the bathwater.

PMID- 25768097
TI  - Feasibility and results of a fast-track protocol in thoracic surgery.
AB  - BACKGROUND: A rehabilitation program, a multimodal strategy favoring rapid
      postoperative return to autonomy, has rarely been undertaken after thoracic
      surgery compared to colectomy. The primary outcome of this fast-track program was
      the length of postoperative stay. Secondary outcomes concerned the feasibility of
      this strategy, the incidence of postoperative complications and 3-month
      postoperative mortality. METHODS: Patients were included in this prospective
      single-center observational study if they were scheduled for lung resection
      (lobectomy or wedge resection) performed by posterolateral thoracotomy. The
      rehabilitation program, coordinated by a referent nurse, included a list of
      actions to be done, especially early feeding and ambulation, multimodal analgesia
      including epidural analgesia, early removal of chest tube. RESULTS: One hundred
      and two patients were included in total with two exclusions (failure of epidural
      analgesia). The postoperative hospital stay was 8 (7-10) days (median [25-75th
      percentiles]); this duration was similar to that of the historical cohort which
      was 9 [7-13] days (P=0.06). Most actions were conducted with a high level of
      acceptance except for the insertion of a single chest tube (19%) and its removal
      later than expected in the program. Only 50% of patients left hospital shortly
      after exit criteria were met suggesting failure in the organization. Patients'
      satisfaction rate reached 77% and no postoperative death was reported during the
      follow-up period. CONCLUSION: A program for early rehabilitation is feasible
      after thoracotomy. Chest drainage and organization to optimize the length of stay
      are crucial points.

PMID- 25768099
TI  - Interventions to treat premature ejaculation: a systematic review short report.
AB  - BACKGROUND: Premature ejaculation (PE) is commonly defined as ejaculation with
      minimal sexual stimulation before, on or shortly after penetration and before the
      person wishes it. PE can be either lifelong and present since first sexual
      experiences (primary), or acquired (secondary), beginning later (Godpodinoff ML.
      Premature ejaculation: clinical subgroups and etiology. J Sex Marital Ther
      1989;15:130-4). Treatments include behavioural and pharmacological interventions.
      OBJECTIVE: To systematically review evidence for clinical effectiveness of
      behavioural, topical and systemic treatments for PE. DATA SOURCES: The following
      databases were searched from inception to 6 August 2013 for published and
      unpublished research evidence: MEDLINE; EMBASE; Cumulative Index to Nursing and
      Allied Health Literature; The Cochrane Library including the Cochrane Systematic
      Reviews Database, Cochrane Controlled Trials Register, Database of Abstracts of
      Reviews of Effects and the Health Technology Assessment database; ISI Web of
      Science, including Science Citation Index, and the Conference Proceedings
      Citation Index-Science. The US Food and Drug Administration website and the
      European Medicines Agency (EMA) website were also searched. METHODS: Randomised
      controlled trials (RCTs) in adult men with PE were eligible (or non-RCTs in the
      absence of RCTs). RCT data were extrapolated from review articles when available.
      The primary outcome was intravaginal ejaculatory latency time (IELT). Data were
      meta-analysed when possible. Other outcomes included sexual satisfaction, control
      over ejaculation, relationship satisfaction, self-esteem, quality of life,
      treatment acceptability and adverse events (AEs). RESULTS: A total of 103 studies
      (102 RCTs, 65 from reviews) were included. RCTs were available for all
      interventions except yoga. The following interventions demonstrated significant
      improvements (p < 0.05) in arithmetic mean difference in IELT compared with
      placebo: topical anaesthetics - eutectic mixture of local anaesthetics
      (EMLA((r)), AstraZeneca), topical eutectic mixture for PE (Plethora Solutions
      Ltd) spray; selective serotonin reuptake inhibitors (SSRIs) - citalopram
      (Cipramil((r)), Lundbeck), escitalopram (Cipralex((r)), Lundbeck), fluoxetine,
      paroxetine, sertraline, dapoxetine (Priligy((r)), Menarini), 30 mg or 60 mg;
      serotonin-noradrenaline reuptake inhibitors - duloxetine (Cymbalta((r)), Eli
      Lilly & Co Ltd); tricyclic antidepressants - inhaled clomipramine 4 mg;
      phosphodiesterase-5 (PDE5) inhibitors - vardenafil (Levitra((r)), Bayer),
      tadalafil (Cialis((r)), Eli Lilly & Co Ltd); opioid analgesics - tramadol (Zydol
      SR((r)), Grunenthal). Improvements in sexual satisfaction and other outcomes
      compared with placebo were evident for SSRIs, PDE5 inhibitors and tramadol.
      Outcomes for interventions not compared with placebo were as follows: behavioural
      therapies - improvements over wait list control in IELT and other outcomes,
      behavioural therapy plus pharmacotherapy better than either therapy alone; alpha
      blockers - terazosin (Hytrin((r)), AMCO) not significantly different to
      antidepressants in ejaculation control; acupuncture - improvements over sham
      acupuncture in IELT, conflicting results for comparisons with SSRIs; Chinese
      medicine - improvements over treatment as usual; delay device - improvements in
      IELT when added to stop-start technique; yoga - improved IELT over baseline,
      fluoxetine better than yoga. Treatment-related AEs were evident with most
      pharmacological interventions. LIMITATIONS: Although data extraction from reviews
      was optimised when more than one review reported data for the same RCT, the
      reliability of the data extraction within these reviews cannot be guaranteed by
      this assessment report. CONCLUSIONS: Several interventions significantly improved
      IELT. Many interventions also improved sexual satisfaction and other outcomes.
      However, assessment of longer-term safety and effectiveness is required to
      evaluate whether or not initial treatment effects are maintained long term,
      whether or not dose escalation is required, how soon treatment effects end
      following treatment cessation and whether or not treatments can be stopped and
      resumed at a later time. In addition, assessment of the AEs associated with long
      term treatment and whether or not different doses have differing AE profiles is
      required. STUDY REGISTRATION: This study is registered as PROSPERO
      CRD42013005289. FUNDING: The National Institute for Health Research Health
      Technology Assessment programme.

PMID- 25768101
TI  - Advances in the treatment of gastroenteropancreatic neuroendocrine tumors.

PMID- 25768100
TI  - Identification of suitable reference genes for gene expression studies in tendons
      from patients with rotator cuff tear.
AB  - Rotator cuff tear is one of the most common causes of shoulder dysfunction. Gene
      expression analysis may be a useful tool for understanding tendon tears and the
      failure of cuff healing, and reverse-transcription quantitative polymerase chain
      reaction (RT-qPCR) has become an effective method for such studies. However, this
      technique requires the use of suitable reference genes for data normalization.
      Here, we evaluate the suitability of six reference genes (18S, ACTB, B2M, GAPDH,
      HPRT1 and TBP) using samples from the rotator cuff tendons of 28 individuals with
      tendon tears (3 tendons regions) and 8 controls (2 tendon regions); for the tear
      patients, we evaluated ruptured and non-ruptured tendon samples. The stability of
      the candidate reference genes was determined using the NormFinder, geNorm,
      BestKeeper and DataAssist software packages. Overall, HPRT1 was the best single
      reference gene, and HPRT1+TBP composed the best pair and HPRT1+TBP+ACTB composed
      the best trio of reference genes from the analysis of different groups, including
      the simultaneous analysis of all tissue samples. To identify the optimal
      combination of reference genes, we evaluated the expression of COL1A1 and COL3A1,
      and no obvious differences were observed when using 2, 3 or 4 reference genes for
      most of the analyses. However, COL3A1 expression differed between ruptured and
      non-ruptured (posterior superior region) tendons of patients only when normalized
      by HPRT1+TBP+B2M and HPRT1+TBP. On the other hand, the comparison between these
      two groups using the best trio of reference genes (HPRT1+TBP+ACTB) and 4
      reference genes did not revealed a significant difference in COL3A1 expression.
      Consequently, the use of suitable reference genes for a reliable gene expression
      evaluation by RT-qPCR should consider the type of tendon samples investigated.
      HPRT1+TBP+ACTB seems to be the best combination of reference genes for the
      analysis of involving different tendon samples of individuals with rotator cuff
      tears. 

PMID- 25768103
TI  - Gastroenteropancreatic neuroendocrine tumors (GEP-NETs): a closer look at the
      characteristics of these diverse tumors.

PMID- 25768104
TI  - New directions in the treatment of gastroenteropancreatic neuroendocrine tumors
      (GEP-NETs): shifting from symptom management to targeting tumors.

PMID- 25768105
TI  - Clinical scenario 1: Advanced, grade 2, neuroendocrine tumor in the midgut.

PMID- 25768106
TI  - Clinical scenario 2: Exploring treatment options for patients with symptomatic,
      progressive GEP-NETs.

PMID- 25768107
TI  - Continued advances in targeting gastroenteropancreatic neuroendocrine tumors:
      general discussion.

PMID- 25768109
TI  - Electronic and vibrational spectra of positive polarons and bipolarons in
      regioregular poly(3-hexylthiophene) doped with ferric chloride.
AB  - We studied the carriers generated in regioregular poly(3-hexylthiophene) (P3HT)
      upon FeCl3 vapor and solution doping using visible/near-infrared (VIS/NIR)
      absorption, infrared (IR), and Raman spectroscopy. Upon doping with an FeCl3
      solution in air, the main carriers that were generated were positive polarons.
      Upon doping with FeCl3 vapor, positive polarons also formed initially, but at
      higher doping levels, positive bipolarons formed with the concomitant
      disappearance of the positive polarons. The Raman and IR spectra of the positive
      bipolarons and the positive polarons were obtained. Raman spectroscopy is very
      useful for characterizing positive polarons and bipolarons. The Raman results
      indicated that the positive bipolarons were converted to polarons upon heating to
      85  degrees C, indicating that the positive bipolarons formed a metastable state.
      The temporal changes in the electrical conductivity of a P3HT film upon doping
      with FeCl3 vapor were measured. The conductivity reached a maximum and then
      decreased by 2 orders of magnitude. This result suggests that the mobility of the
      polarons is approximately 100 times as high as that of the bipolarons. 

PMID- 25768108
TI  - Z-Spectrum analysis provides proton environment data (ZAPPED): a new two-pool
      technique for human gray and white matter.
AB  - A new technique - Z-spectrum Analysis Provides Proton Environment Data (ZAPPED) -
      was used to map cross-relaxing free and restricted protons in nine healthy
      subjects plus two brain tumor patients at 3T. First, MT data were acquired over a
      wide symmetric range of frequency offsets, and then a trio of quantitative
      biomarkers, i.e., the apparent spin-spin relaxation times (T2,f, T2,r) in both
      free and restricted proton pools as well as the restricted pool fraction Fr, were
      mapped by fitting the measured Z-spectra to a simple two-Lorentzian compartment
      model on a voxel-by-voxel basis. The mean restricted exchangeable proton
      fraction, Fr, was found to be 0.17 in gray matter (GM) and 0.28 in white matter
      (WM) in healthy subjects. Corresponding mean values for apparent spin-spin
      relaxation times were 785 us (T2,f) and 17.7 us (T2,r) in GM, 672 us (T2,f) and
      23.4 us (T2,r) in WM. The percentages of Ff and Fr in GM are similar for all
      ages, whereas Fr shows a tendency to decrease with age in WM among healthy
      subjects. The patient ZAPPED images show higher contrast between tumor and normal
      tissues than traditional T2-weighted and T1-weighted images. The ZAPPED method
      provides a simple phenomenological approach to estimating fractions and apparent
      T2 values of free and restricted MT-active protons, and it may offer clinical
      useful information. 

PMID- 25768110
TI  - Deep sequencing and ecological characterization of gut microbial communities of
      diverse bumble bee species.
AB  - Gut bacterial communities of bumble bees are correlated with defense against
      pathogens. Further understanding this host-microbe association is vitally
      important as bumble bees are currently experiencing global population declines,
      potentially due in part to emergent diseases. In this study, we used
      pyrosequencing and community fingerprinting (ARISA) to characterize the gut
      microbial communities of nine bumble species from across the Bombus phylogeny.
      Overall, we delimited 74 bacterial taxa (operational taxonomic units or OTUs)
      belonging to Betaproteobacteria, Gammaproteobacteria, Bacilli, Actinobacteria,
      Flavobacteria and Alphaproteobacteria. Each bacterial community was taxonomically
      simple, containing an average of 1.9 common (relative abundance per sample > 5%)
      bacterial OTUs. The most abundant and prevalent (occurring in 92% of the samples)
      bacterial OTU, based on 16S rRNA sequences, closely matched that of the
      previously described Betaproteobacteria species Snodgrassella alvi. Bacteria that
      were first described in bee-related external environments dominated a number of
      gut bacterial communities, suggesting that they are not strictly dependent on the
      internal gut environment. The ARISA data showed a correlation between bacterial
      community structures and the geographic locations where the bees were sampled,
      suggesting that at least a subset of the bacterial species may be transmitted
      environmentally. Using light and fluorescent microscopy, we demonstrated that the
      gut bacteria form a biofilm on the internal epithelial surface of the ileum,
      corroborating results obtained from Apis mellifera. 

PMID- 25768111
TI  - Vigilance and activity time-budget adjustments of wintering hooded cranes, Grus
      monacha, in human-dominated foraging habitats.
AB  - Due to loss and degradation of natural wetlands, waterbirds increasingly rely on
      surrounding human-dominated habitats to obtain food. Quantifying vigilance
      patterns, investigating the trade-off among various activities, and examining the
      underlying mechanisms will help us understand how waterbirds adapt to human
      caused disturbances. During two successive winters (November-February of 2012-13
      and 2013-14), we studied the hooded crane, Grus monacha, in the Shengjin Lake
      National Nature Reserve (NNR), China, to investigate how the species responds to
      human disturbances through vigilance and activity time-budget adjustments. Our
      results showed striking differences in the behavior of the cranes when foraging
      in the highly disturbed rice paddy fields found in the buffer zone compared with
      the degraded natural wetlands in the core area of the NNR. Time spent vigilant
      decreased with flock size and cranes spent more time vigilant in the human
      dominated buffer zone. In the rice paddy fields, the birds were more vigilant but
      also fed more at the expense of locomotion and maintenance activities. Adult
      cranes spent more time vigilant and foraged less than juveniles. We recommend
      habitat recovery in natural wetlands and community co-management in the
      surrounding human-dominated landscape for conservation of the hooded crane and,
      generally, for the vast numbers of migratory waterbirds wintering in the middle
      and lower reaches of the Yangtze River floodplain. 

PMID- 25768113
TI  - Chain conformation and dynamics in spin-assisted weak polyelectrolyte
      multilayers.
AB  - We report on the effect of the deposition technique on film layering, stability,
      and chain mobility in weak polyelectrolyte layer-by-layer (LbL) films.
      Ellipsometry and neutron reflectometry (NR) showed that shear forces arising
      during spin-assisted assembly lead to smaller amounts of adsorbed
      polyelectrolytes within LbL films, result in a higher degree of internal film
      order, and dramatically improve stability of assemblies in salt solutions as
      compared to dip-assisted LbL assemblies. The underlying flattening of
      polyelectrolyte chains in spin-assisted LbL films was also revealed as an
      increase in ionization degree of the assembled weak polyelectrolytes. As
      demonstrated by fluorescence recovery after photobleaching (FRAP), strong binding
      between spin-deposited polyelectrolytes results in a significant slowdown of
      chain diffusion in salt solutions as compared to dip-deposited films. Moreover,
      salt-induced chain intermixing in the direction perpendicular to the substrate is
      largely inhibited in spin-deposited films, resulting in only subdiffusional (<2
      A) chain displacements even after 200 h exposure to 1 M NaCl solutions. This
      persistence of polyelectrolyte layering has important ramifications for
      multistage drug delivery and optical applications of LbL assemblies. 

PMID- 25768112
TI  - Associations of objectively assessed physical activity and sedentary time with
      all-cause mortality in US adults: the NHANES study.
AB  - BACKGROUND: Sedentary behavior is related to increased mortality risk. Whether
      such elevated risk can be offset by enhanced physical activity has not been
      examined using accelerometry data. MATERIALS AND METHODS: We examined the
      relations of sedentary time and physical activity to mortality from any cause
      using accelerometry data among 1,677 women and men aged 50 years or older from
      the National Health and Nutrition Examination Survey (NHANES) 2003-2004 cycle
      with follow-up through December 31, 2006. RESULTS: During an average follow-up of
      34.67 months and 4,845.42 person-years, 112 deaths occurred. In multivariate Cox
      proportional hazard models, greater sedentary time (>= median of 8.60 hours/day)
      was associated with increased risk of mortality from any cause (relative risk
      (RR) = 2.03; 95% confidence interval (CI) = 1.09-3.81). Low level of moderate to
      vigorous physical activity (< median of 6.60 minutes/day) was also related to
      enhanced all-cause mortality risk (RR = 3.30; 95% CI = 1.33-8.17). In combined
      analyses, greater time spent sedentary and low levels of moderate to vigorous
      physical activity predicted a substantially elevated all-cause mortality risk. As
      compared with the combination of a low sedentary level and a high level of
      moderate to vigorous physical activity, the risks of mortality from all causes
      were 4.38 (95% CI = 1.26-15.16) for low levels of both sedentary time and
      physical activity, 2.79 (95% CI = 0.77-10.12) for greater time spent sedentary
      and high physical activity level, and 7.79 (95% CI = 2.26-26.82) for greater time
      spent sedentary and low physical activity level. The interaction term between
      sedentary time and moderate to vigorous physical activity was not statistically
      significant (p = 0.508). CONCLUSIONS: Both high levels of sedentary time and low
      levels of moderate to vigorous physical activity are strong and independent
      predictors of early death from any cause. Whether a high physical activity level
      removes the increased risk of all-cause mortality related to sedentariness
      requires further investigation.

PMID- 25768114
TI  - Correction: UFSRAT: Ultra-Fast Shape Recognition with Atom Types--the discovery
      of novel bioactive small molecular scaffolds for FKBP12 and 11betaHSD1.

PMID- 25768115
TI  - The in vitro antifungal activity of sudanese medicinal plants against Madurella
      mycetomatis, the eumycetoma major causative agent.
AB  - Eumycetoma is a debilitating chronic inflammatory fungal infection that exists
      worldwide but it is endemic in many tropical and subtropical regions. The major
      causative organism is the fungus Madurella mycetomatis. The current treatment of
      eumycetoma is suboptimal and characterized by low cure rate and high recurrence
      rates. Hence, an alternative therapy is needed to address this. Here we
      determined the antifungal activity of seven Sudanese medicinal plant species
      against Madurella mycetomatis. Of these, only three species; Boswellia
      papyrifera, Acacia nubica and Nigella sativa, showed some antifungal activity
      against M. mycetomatis and were further studied. Crude methanol, hexane and
      defatted methanol extracts of these species were tested for their antifungal
      activity. B. papyrifera had the highest antifungal activity (MIC50 of 1 ug/ml)
      and it was further fractionated. The crude methanol and the soluble ethyl acetate
      fractions of B. papyrifera showed some antifungal activity. The Gas-Liquid
      Chromatography hybrid Mass-Spectrophotometer analysis of these two fractions
      showed the existence of beta-amyrin, beta-amyrone, beta-Sitosterol and
      stigmatriene. Stigmatriene had the best antifungal activity, compared to other
      three phytoconstituents, with an MIC-50 of 32 MUg/ml. Although the antifungal
      activity of the identified phytoconstituents was only limited, the antifungal
      activity of the complete extracts is more promising, indicating synergism.
      Furthermore these plant extracts are also known to have anti-inflammatory
      activity and can stimulate wound-healing; characteristics which might also be of
      great value in the development of novel therapeutic drugs for this chronic
      inflammatory disease. Therefore further exploration of these plant species in the
      treatment of mycetoma is encouraging. 

PMID- 25768116
TI  - The exocyst complex regulates free fatty acid uptake by adipocytes.
AB  - The exocyst is an octameric molecular complex that drives vesicle trafficking in
      adipocytes, a rate-limiting step in insulin-dependent glucose uptake. This study
      assessed the role of the exocyst complex in regulating free fatty acid (FFA)
      uptake by adipocytes. Upon differentiating into adipocytes, 3T3-L1 cells acquire
      the ability to incorporate extracellular FFAs in an insulin-dependent manner. A
      kinetic assay using fluoresceinated FFA (C12 dodecanoic acid) uptake allows the
      real-time monitoring of FFA internalization by adipocytes. The insulin-dependent
      uptake of C12 dodecanoic acid by 3T3-L1 adipocytes is mediated by Akt and
      phosphatidylinositol 3 (PI3)-kinase. Gene silencing of the exocyst components
      Exo70 and Sec8 significantly reduced insulin-dependent FFA uptake by adipocytes.
      Consistent with the roles played by Exo70 and Sec8 in FFA uptake, mCherry-tagged
      Exo70 and HA-tagged Sec8 partially colocalize with lipid droplets within
      adipocytes, suggesting their active roles in the development of lipid droplets.
      Tubulin polymerization was also found to regulate FFA uptake in collaboration
      with the exocyst complex. This study demonstrates a novel role played by the
      exocyst complex in the regulation of FFA uptake by adipocytes. 

PMID- 25768117
TI  - Diapers in war zones: ethnomedical factors in acute childhood gastroenteritis in
      Peshawar, Pakistan.
AB  - This article considers ethnomedical knowledge and practices among parents related
      to contraction of acute gastroenteritis among children in Peshawar, Pakistan.
      Research methods included analysis of the Emergency Pediatric Services' admission
      register, a structured interview administered to 47 parents of patients seen in
      the Khyber Medical College Teaching Hospital, semi-structured interviews of 12
      staff, and four home visits among families with children treated at the hospital.
      The use of native research assistants and participant observation contributed to
      the reliability of the findings, though the ethnographic, home-visit sample is
      small. Our research indicated that infection rates are exacerbated in homes
      through two culturally salient practices and one socioeconomic condition. Various
      misconceptions propagate the recurrence or perserverance of acute gastroenteritis
      including assumptions about teething leading to poor knowledge of disease
      etiology, rehydration solutions leading to increased severity of disease, and
      diaper usage leading to the spread of disease. In our Discussion, we suggest how
      hospital structures of authority and gender hierarchy may impact hospital
      interactions, the flow of information, and its respective importance to the
      patient's parents leading to possible propagation of disease. These ethnographic
      data offer a relatively brief but targeted course of action to improve the
      effectiveness of prevention and treatment efforts. 

PMID- 25768118
TI  - TEM and SP-ICP-MS analysis of the release of silver nanoparticles from decoration
      of pastry.
AB  - Metallic silver is an EU approved food additive referred to as E174. It is
      generally assumed that silver is only present in bulk form in the food chain.
      This work demonstrates that a simple treatment with water of "silver pearls",
      meant for decoration of pastry, results in the release of a subfraction of silver
      nanoparticles. The number-based size and shape distributions of the single,
      aggregated, and/or agglomerated particles released from the silver pearls were
      determined by combining conventional bright-field TEM imaging with semiautomatic
      particle detection and analysis. In addition, the crystal structure of the
      particles was studied by electron diffraction and chemical information was
      obtained by combining HAADF-STEM imaging with EDX spectroscopy and mapping. The
      TEM results were confirmed by SP-ICP-MS. The representative Ag test nanomaterial
      NM-300 K was used as a positive control to determine the uncertainty on the
      measurement of the size and shape of the particles.

PMID- 25768119
TI  - A zinc finger motif-containing protein is essential for chloroplast RNA editing.
AB  - C-to-U editing of transcripts in plant organelles is carried out by small (<400
      kD) protein complexes called editosomes. Recognition of the proper C target for
      editing is mediated by pentatricopeptide repeat (PPR) containing proteins that
      recognize cis-elements. Members of two additional gene families, the RIP/MORF and
      ORRM families, have each been found to be required for editing of particular sets
      of Cs in mitochondria and/or chloroplasts. By co-immunoprecipitation of the
      chloroplast editing factor ORRM1, followed by mass spectrometry, we have now
      identified a member of the RanBP2 type zinc fingers (pFAM00641) protein family
      that is required for editing of 14 sites in chloroplasts and affects editing
      efficiency of another 16 chloroplast C targets. In yeast two-hybrid assays, OZ1
      (Organelle Zinc finger 1) interacts with PPR site recognition factors whose
      cognate sites are affected when OZ1 is mutated. No interaction of OZ1 with the
      chloroplast editing factors RIP2 and RIP9 was detected; however, OZ1 interacts
      with ORRM1, which binds to RIP proteins, allowing us to build a model for the
      chloroplast RNA editosome. The RNA editosomes that act upon most chloroplast C
      targets are likely to contain a PPR protein recognition factor, either RIP2 or
      RIP9, ORRM1, and OZ1. The organelle zinc finger editing factor family (OZ)
      contains 4 members in Arabidopsis, three that are predicted to be targeted to
      chloroplasts and one to mitochondria. With the identification of OZ1, there are
      now 4 nuclear-encoded protein families known to be essential for plant organelle
      RNA editing. 

PMID- 25768120
TI  - Irritable brain caused by irritable bowel? A nationwide analysis for irritable
      bowel syndrome and risk of bipolar disorder.
AB  - OBJECTIVE: We explored the association between IBS and the development of bipolar
      disorder, and the risk factors for bipolar disorders in patients with IBS.
      METHODS: We identified patients who were newly diagnosed with IBS between 2000
      and 2010 in the Taiwan National Health Insurance Research Database. We also
      identified a comparison matched cohort without IBS. The occurrence of new-onset
      bipolar disorder was evaluated in both cohorts. RESULTS: The IBS cohort consisted
      of 30,796 patients and the comparison cohort consisted of 30,796 matched patients
      without IBS. The incidence of bipolar disorder (incidence rate ratio, 2.63, 95%
      confidence interval (CI) 2.10-3.31, P < .001) was higher in the IBS patients than
      in the matched cohort. Multivariate matched regression models indicated that
      autoimmune diseases (HR 1.52, 95% CI 1.07-2.17, P = .020), and asthma (HR 1.45,
      95% CI 1.08-1.95, P = .013) were independent risk factors for the development of
      bipolar disorder in the IBS patients. CONCLUSION: IBS may increase the risk of
      developing subsequent bipolar disorder. Additional prospective studies are
      required to confirm these findings.

PMID- 25768121
TI  - Low hemoglobin level is associated with the development of delirium after
      hepatectomy for hepatocellular carcinoma patients.
AB  - BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most common malignant
      tumors worldwide and liver resection is the only potential curative treatment
      option for those patients. Postoperative complications specific to elderly
      surgical patients such as delirium will be increasingly relevant in the coming
      decades. Herein, we aimed to investigate the risk factors for postoperative
      delirium in patients who have received hepatectomy for HCC. METHODS: This is a
      single medical center observational study and the study subjects comprised 401
      individuals who underwent liver resection for hepatocellular carcinoma during
      January 2009 to October 2013. Multivariate analysis was used to examine whether
      preoperative, intra-operative, or postoperative variables were associated with
      the development of delirium. RESULTS: Of the 401 patients who underwent
      hepatectomy, 34 developed postoperative delirium (8.4%). In the majority of those
      patients, symptoms and signs of the syndrome occurred on postoperative day 2 and
      the mean duration of symptoms was 3.61 +/- 3.71 days. Multivariate analysis
      revealed that advanced age (>71 years) [odds ratio (OR) = 1.133, 95% confidence
      interval (CI): 1.071-1.200, p<0.001], prolonged operative time (>190 minutes) (OR
      = 1.009, 95% CI: 1.000-1.017, p = 0.038), a decreased postoperative hemoglobin
      level (< 10.16 g/dL) (OR = 0.777, 95% CI: 0.613-0.983, p = 0.036), and history of
      hypnotic drug use (OR = 3.074, 95% CI: 1.045-9.039, p = 0.041) were independent
      risk factors for the development of postoperative delirium after hepatectomy.
      CONCLUSIONS: Although the mechanism of postoperative delirium is not well
      understood, numbers of studies have shown that patients with postoperative
      delirium tend to have prolonged hospital stay, worse postoperative outcome and an
      increased risk of short- and long-term mortality. In this study, we found that
      advanced age, prolonged operative time, postoperative low hemoglobin level and
      history of hypnotic drug use are independent risk factors for postoperative
      delirium.

PMID- 25768122
TI  - Hybrid paclitaxel and gold nanorod-loaded human serum albumin nanoparticles for
      simultaneous chemotherapeutic and photothermal therapy on 4T1 breast cancer
      cells.
AB  - The use of human serum albumin nanoparticles (HSAPs) as a drug carrier system for
      cancer treatment has proven successful through current marketable clinical
      formulations. Despite this success, there is a current lack of multifunctional
      HSAPs, which offer combinational therapies of more than one proven technique.
      Gold nanorods (AuNRs) have also shown medicinal promise due to their photothermal
      therapy capabilities. In this study, a desolvation and cross-linking approach was
      employed to successfully encapsulate gold nanorods into HSAPs simultaneously with
      the chemotherapeutic drug paclitaxel (PAC); forming PAC-AuNR-HSAPs with desirable
      overall particle sizes of 299 +/- 6 nm. The loading efficiency of paclitaxel into
      PAC-AuNR-HSAPs reached up to 3 MUg PAC/mg HSA. The PAC-AuNR-HSAPs experienced
      photothermal heating; with the bulk particle solution reaching up to 46  degrees
      C after 15 min of near-IR laser exposure. This heat increase marked the
      successful attainment of the temperature necessary to cause severe cellular
      hyperthermia and necrosis. The encasement strategy facilitated a colloidal hybrid
      treatment system capable of enhanced permeability and retention effects,
      photothermal ablation of cancer cells, and release of the active paclitaxel of up
      to 188 ng (from PAC-AuNR-HSAPs created with 30 mg HSA) in a single 15 min
      irradiation session. When treated with PAC-AuNR-HSAPs containing 20 MUg PAC/mL
      particle solution, 4T1 mouse breast cancer cells experienced ~82% cell death
      without irradiation and ~94% cell death after just one irradiation session. The
      results for PAC-AuNR-HSAPs were better than that of free PAC, which only killed
      ~77% of the cells without irradiation and ~80% with irradiation. The hybrid
      particle system also lends itself to future customizable external functionalities
      via conjugated targeting ligands, such as antibodies. Internal entrapment of
      patient tailored medication combinations are also possible with this combination
      treatment platform, which may result in improved quality of life for those
      undergoing treatment. 

PMID- 25768123
TI  - Shoulder kinematics and spatial pattern of trapezius electromyographic activity
      in real and virtual environments.
AB  - The design of an industrial workstation tends to include ergonomic assessment
      steps based on a digital mock-up and a virtual reality setup. Lack of interaction
      and system fidelity is often reported as a main issue in such virtual reality
      applications. This limitation is a crucial issue as thorough ergonomic analysis
      is required for an investigation of the biomechanics. In the current study, we
      investigated the biomechanical responses of the shoulder joint in a simulated
      assembly task for comparison with the biomechanical responses in virtual
      environments. Sixteen male healthy novice subjects performed the task on three
      different platforms: real (RE), virtual (VE), and virtual environment with force
      feedback (VEF) with low and high precision demands. The subjects repeated the
      task 12 times (i.e., 12 cycles). High density electromyography from the upper
      trapezius and rotation angles of the shoulder joint were recorded and split into
      the cycles. The angular trajectories and velocity profiles of the shoulder joint
      angles over a cycle were computed in 3D. The inter-subject similarity in terms of
      normalized mutual information on kinematics and electromyography was
      investigated. Compared with RE the task in VE and VEF was characterized by lower
      kinematic maxima. The inter-subject similarity in RE compared with intra-subject
      similarity across the platforms was lower in terms of movement trajectories and
      greater in terms of trapezius muscle activation. The precision demand resulted in
      lower inter- and intra-subject similarity across platforms. The proposed approach
      identifies biomechanical differences in the shoulder joint in both VE and VEF
      compared with the RE platform, but these differences are less marked in VE mostly
      due to technical limitations of co-localizing the force feedback system in the
      VEF platform. 

PMID- 25768124
TI  - Metal-free tetrathienoacene sensitizers for high-performance dye-sensitized solar
      cells.
AB  - A new series of metal-free organic chromophores (TPA-TTAR-A (1), TPA-T-TTAR-A
      (2), TPA-TTAR-T-A (3), and TPA-T-TTAR-T-A (4)) are synthesized for application in
      dye-sensitized solar cells (DSSC) based on a donor-pi-bridge-acceptor (D-pi-A)
      design. Here a simple triphenylamine (TPA) moiety serves as the electron donor, a
      cyanoacrylic acid as the electron acceptor and anchoring group, and a novel
      tetrathienoacene (TTA) as the pi-bridge unit. Because of the extensively
      conjugated TTA pi-bridge, these dyes exhibit high extinction coefficients (4.5
      5.2 * 10(4) M(-1) cm(-1)). By strategically inserting a thiophene spacer on the
      donor or acceptor side of the molecules, the electronic structures of these TTA
      based dyes can be readily tuned. Furthermore, addition of a thiophene spacer has
      a significant influence on the dye orientation and self-assembly modality on TiO2
      surfaces. The insertion of a thiophene between the pi-bridge and the cyanoacrylic
      acid anchoring group in TPA-TTAR-T-A (dye 3) promotes more vertical dye
      orientation and denser packing on TiO2 (molecular footprint = 79 A(2)), thus
      enabling optimal dye loading. Using dye 3, a DSSC power conversion efficiency
      (PCE) of 10.1% with Voc = 0.833 V, Jsc = 16.5 mA/cm(2), and FF = 70.0% is
      achieved, among the highest reported to date for metal-free organic DSSC
      sensitizers using an I(-)/I3(-) redox shuttle. Photophysical measurements on dye
      grafted TiO2 films reveal that the additional thiophene unit in dye 3 enhances
      the electron injection efficiency, in agreement with the high quantum efficiency.

PMID- 25768125
TI  - Quantitative effect of a CNV on a morphological trait in chickens.
AB  - Copy Number Variation has been associated with morphological traits,
      developmental defects or disease susceptibility. The autosomal dominant Pea-comb
      mutation in chickens is due to the massive amplification of a CNV in intron 1 of
      SOX5 and provides a unique opportunity to assess the effect of variation in the
      number of repeats on quantitative traits such as comb size and comb mass in Pea
      comb chickens. The quantitative variation of comb size was estimated by 2D
      morphometry and the number of repeats (RQ) was estimated by qPCR, in a total of
      178 chickens from 3 experimental lines, two of them showing segregation for the
      Pea-comb mutation. This study included only Pea-comb chickens. Analysis of
      variance showed highly significant effects of line and sex on comb measurements.
      Adult body weight (BW) and RQ were handled as covariates. BW significantly
      influenced comb mass but not comb size. RQ values significantly influenced comb
      size, and the linear regression coefficient was highest for heterozygous
      carriers: the higher the number of repeats, the smaller the comb size. A similar
      trend was observed for comb mass. The CNV contributed to 3.4% of the phenotypic
      variance of comb size in heterozygous carriers of the CNV, an order of magnitude
      frequently encountered for QTLs. Surprisingly, there was no such relationship
      between RQ values and comb size in the homozygous line. It may be concluded that
      heterozygosity for a CNV in a non-coding region may contribute to phenotypic
      plasticity. 

PMID- 25768127
TI  - Synthesis of polysubstituted quinolines via transition-metal-free oxidative
      cycloisomerization of o-cinnamylanilines.
AB  - An efficient synthesis of 2-aryl 4-substituted quinolines from stable and readily
      available o-cinnamylanilines, prepared from anilines and cinnamylalcohols, has
      been developed. The reaction occurred via a regioselective 6-endo-trig
      intramolecular oxidative cyclization using KO(t)Bu as a mediator and DMSO as an
      oxidant at rt. The reaction showed a broad substrate scope with good to excellent
      yields. 

PMID- 25768128
TI  - Activation of CH4 by Th(+) as studied by guided ion beam mass spectrometry and
      quantum chemistry.
AB  - The reaction of atomic thorium cations with CH4 (CD4) and the collision-induced
      dissociation (CID) of ThCH4(+) with Xe are studied using guided ion beam tandem
      mass spectrometry. In the methane reactions at low energies, ThCH2(+) (ThCD2(+))
      is the only product; however, the energy dependence of the cross-section is
      inconsistent with a barrierless exothermic reaction as previously assumed on the
      basis of ion cyclotron resonance mass spectrometry results. The dominant product
      at higher energies is ThH(+) (ThD(+)), with ThCH3(+) (ThCD3(+)) having a similar
      threshold energy. The latter product subsequently decomposes at still higher
      energies to ThCH(+) (ThCD(+)). CID of ThCH4(+) yields atomic Th(+) as the
      exclusive product. The cross-sections of all product ions are modeled to provide
      0 K bond dissociation energies (in eV) of D0(Th(+)-H) >= 2.25 +/- 0.18, D0(Th(+)
      CH) = 6.19 +/- 0.16, D0(Th(+)-CH2) >= 4.54 +/- 0.09, D0(Th(+)-CH3) = 2.60 +/-
      0.30, and D0(Th(+)-CH4) = 0.47 +/- 0.05. Quantum chemical calculations at several
      levels of theory are used to explore the potential energy surfaces for activation
      of methane by Th(+), and the effects of spin-orbit coupling are carefully
      considered. When spin-orbit coupling is explicitly considered, a barrier for C-H
      bond activation that is consistent with the threshold measured for ThCH2(+)
      formation (0.17 +/- 0.02 eV) is found at all levels of theory, whereas this
      barrier is observed only at the BHLYP and CCSD(T) levels otherwise. The
      observation that the CID of the ThCH4(+) complex produces Th(+) as the only
      product with a threshold of 0.47 eV indicates that this species has a Th(+)(CH4)
      structure, which is also consistent with a barrier for C-H bond activation. This
      barrier is thought to exist as a result of the mixed ((4)F,(2)D) electronic
      character of the Th(+) J = (3)/2 ground level combined with extensive spin-orbit
      effects. 

PMID- 25768126
TI  - IbeR facilitates stress-resistance, invasion and pathogenicity of avian
      pathogenic Escherichia coli.
AB  - Systemic infections by avian pathogenic Escherichia coli (APEC) are economically
      devastating to poultry industries worldwide. IbeR, located on genomic island
      GimA, was shown to serve as an RpoS-like regulator in rpoS gene mutation neonatal
      meningitis E. coli (NMEC) RS218. However, the role of IbeR in pathogenicity of
      APEC carrying active RpoS has not yet been investigated. We showed that the APEC
      IbeR could elicit antibodies in infected ducks, suggesting that IbeR might be
      involved in APEC pathogenicity. To investigate the function of IbeR in APEC
      pathogenesis, mutant and complementation strains were constructed and
      characterized. Inactivation of ibeR led to attenuated virulence and reduced
      invasion capacity towards DF-1 cells, brains and cerebrospinal fluid (CSF) in
      vitro and in vivo. Bactericidal assays demonstrated that the mutant strain had
      impaired resistance to environmental stress and specific pathogen-free (SPF)
      chicken serum. These virulence-related phenotypes were restored by genetic
      complementation. Quantitative real-time reverse transcription PCR revealed that
      IbeR controlled expression of stress-resistance genes and virulence genes, which
      might led to the associated virulence phenotype. 

PMID- 25768129
TI  - Subwavelength binary plasmonic solitons.
AB  - We study the formation of subwavelength solitons in binary metal-dielectric
      lattices. We show that the transverse modulation of the lattice constant breaks
      the fundamental plasmonic band and suppresses the discrete diffraction of surface
      plasmon waves. New types of plasmonic solitons are found, and their
      characteristics are analyzed. We also demonstrate the existence of photonic
      plasmonic vector solitons and elucidate their propagation properties. 

PMID- 25768130
TI  - 1-J operation of monolithic composite ceramics with Yb:YAG thin layers: multi
      TRAM at 10-Hz repetition rate and prospects for 100-Hz operation.
AB  - Experimental amplification of 10-ns pulses to energy of 1 J at repetition rate of
      10-100 Hz in cryogenic multipass total-reflection active-mirror (TRAM) amplifier
      is reported for the first time. By using a monolithic multi-TRAM, which is a YAG
      ceramic composite with three thin Yb:YAG active layers, efficient energy
      extraction was achieved without parasitic lasing. A detailed measurement of
      output characteristics of the laser amplifier is presented; results are discussed
      and compared with numerical calculations. 

PMID- 25768131
TI  - Information encryption in phase space.
AB  - In this Letter, we propose an information encryption technique based on the
      theory of phase-space optics. We show that encoding the plaintext in phase space
      provides a higher level of security: first, the key-space is significantly
      enlarged. Second, it is immune to various known-plaintext (cyphertext) attacks to
      which the double-random phase encryption (DRPE) is vulnerable. Third, the
      bilinearity of phase-space distributions offers additional security. Theoretical
      analysis and numerical calculation results show that the proposed technique has
      significantly different responses to errors added to the cypheretext and the two
      phase keys in comparison to the classical DRPE. 

PMID- 25768132
TI  - Markovian optical modes.
AB  - We describe the transition of a set of optical modes following a Markov chain
      process, where the mean value of the amplitude converge to a new type of
      partially coherent mode, with the property that the coherence features are easily
      tunable with the parameters of the chain. The amplitude of the resulting mode
      depends on the probability transition of the chain. As a prototype, we establish
      an analogy with gambler's chain ruin, using as a basis for the vector space the
      Bessel modes of integer order. Computer simulations are shown. 

PMID- 25768133
TI  - Optical bistability of localized Josephson surface plasmons in cuprate
      superconductors.
AB  - Microparticles made of high-T<sub>c</sub> cuprate superconductors are
      characterized by localized plasmonic excitations known as Josephson surface
      plasmons, whose electromagnetic response is intrinsically nonlinear, giving rise
      to yet unexplored optical phenomena. In this work bistability effects in the near
      resonance excitation of Josephson surface plasmons of dipolar symmetry are
      investigated for spheroidal superconducting particles. The threshold for the
      incident intensity is estimated, and experimental probing strategies are
      discussed. The system can be of interest in view of terahertz light switching and
      detection. 

PMID- 25768134
TI  - Optical reflection modulation using surface plasmon resonance in a graphene
      embedded hybrid plasmonic waveguide at an optical communication wavelength.
AB  - We propose a high-performance, graphene-based optical modulator with a surface
      plasmon resonance (SPR) at 1550 nm. In the proposed device, a graphene layer is
      embedded in a hybrid plasmonic waveguide to enhance the light-graphene
      interaction. The adjustment of the permittivity of the graphene causes a
      significant modulation of the absorption in the SPR through a variation of the
      field confinement in the graphene layer, in addition to a resonant angle shift.
      With an optimal thickness of a metal (Ag) film and the properly chosen operation
      point of the Fermi level of graphene, a modulation depth of ~100% was achieved.
      As the number of graphene layers in the proposed device increases, the insertion
      loss decreases. With five-layer graphene, a 6% insertion loss was achieved. 

PMID- 25768135
TI  - Continuous wave-pumped wavelength conversion in low-loss silicon nitride
      waveguides.
AB  - In this Letter we introduce a complementary metal-oxide semiconductor (CMOS)
      compatible low-loss Si<sub>3</sub>N<sub>4</sub> waveguide platform for nonlinear
      integrated optics. The waveguide has a moderate nonlinear coefficient of 285 
      W/km, but the achieved propagation loss of only 0.06  dB/cm and the ability to
      handle high optical power facilitate an optimal waveguide length for wavelength
      conversion. We observe a constant quadratic dependence of the four-wave mixing
      (FWM) process on the continuous-wave (CW) pump when operating in the C-band,
      which indicates that the waveguide has negligible high-power constraints owing to
      nonlinear losses. We achieve a conversion efficiency of -26.1  dB and idler power
      generation of -19.6  dBm. With these characteristics, we present for the first
      time, to the best of our knowledge, CW-pumped data conversion in a non-resonant
      Si<sub>3</sub>N<sub>4</sub> waveguide. 

PMID- 25768136
TI  - Observation of a classical Cheshire cat in an optical interferometer.
AB  - A recent neutron interferometry experiment claims to demonstrate a paradoxical
      phenomenon dubbed the "quantum Cheshire cat" [Nat. Commun.5, 4492 (2014)]. We
      have reproduced and extended these results with an equivalent optical
      interferometer. The results suggest that the photon travels through one arm of
      the interferometer, while its polarization travels through the other. However, we
      show that these experimental results belong to the domain where quantum and
      classical wave theories coincide; there is nothing uniquely quantum about the
      illusion of this Cheshire cat. 

PMID- 25768137
TI  - Improving cross-modal face recognition using polarimetric imaging.
AB  - We investigate the performance of polarimetric imaging in the long-wave infrared
      (LWIR) spectrum for cross-modal face recognition. For this work, polarimetric
      imagery is generated as stacks of three components: the conventional thermal
      intensity image (referred to as S<sub>0</sub>), and the two Stokes images,
      S<sub>1</sub> and S<sub>2</sub>, which contain combinations of different
      polarizations. The proposed face recognition algorithm extracts and combines
      local gradient magnitude and orientation information from S<sub>0</sub>,
      S<sub>1</sub>, and S<sub>2</sub> to generate a robust feature set that is well
      suited for cross-modal face recognition. Initial results show that polarimetric
      LWIR-to-visible face recognition achieves an 18% increase in Rank-1
      identification rate compared to conventional LWIR-to-visible face recognition. We
      conclude that a substantial improvement in automatic face recognition performance
      can be achieved by exploiting the polarization-state of radiance, as compared to
      using conventional thermal imagery. 

PMID- 25768138
TI  - Two-mode injection-locked FP laser receiver: a regenerator for long-distance
      stable fiber delivery of radio-frequency standards.
AB  - We propose and experimentally validate a new cost-effective optical receiver
      regenerator scheme for long-distance microwave-frequency standard dissemination,
      based on the properties of dual-wavelength injection locked Fabry-Perot (FP)
      lasers. The regenerator FP laser is injection locked to one of its longitudinal
      modes by the incoming intensity-modulated light carrying the microwave-frequency
      standard. The light of a local CW laser is also injected in the regenerator FP,
      locking it to an adjacent mode. The dual-injection locked laser reproduces the
      sinusoidal microwave-frequency standard on both wavelengths. The regenerated
      original signal is transmitted to the next node, whilst the local wavelength is
      fed back to the previous node for phase error extraction and link compensation.
      The performance of the proposed regenerator is demonstrated with Allan deviation
      and phase-noise measurements. 

PMID- 25768139
TI  - Influence of graphene coating on speckle-pattern rotation of light in gyrotropic
      optical fiber.
AB  - In the present work, change in speckle-pattern of linearly polarized light passed
      through graphene-covered optical fiber placed in external magnetic field is
      investigated. The possibility of magnetic speckle-pattern rotation suppression
      and inverse speckle-pattern rotation effect is shown. This effect can be
      controlled by a chemical potential of graphene layer, which can be changed easily
      by a gate voltage, for example. For quartz optical fiber at wavelength 0.633 MUm,
      core diameter 9 MUm, and fiber length 5 cm, an inverse rotation value of 17
      degrees  is reached at chemical potential of graphene layer about 1 eV and
      magnetic field strength 30 kOe. Results of the work may be useful for different
      magneto-optics, opto-electronics, and photonics applications. 

PMID- 25768140
TI  - Coupling-length phase matching for efficient third-harmonic generation based on
      parallel-coupled waveguides.
AB  - We study third-harmonic generation (THG) in parallel-coupled waveguides where the
      spatial modulation of the mode intensity provides quasi-phase matching, called
      coupling-length phase matching (CLPM), for efficient nonlinear frequency
      conversion. Different types of CLPM are investigated for THG, and it is found
      that two sets of CLPM conditions can be practically implemented with traditional
      waveguides. These two CLPM conditions are further investigated by considering
      nonlinear phase modulations, which can degrade the CLPM-based THG conversion.
      However, up to 45% efficiency is still possible in this scheme. The greatest
      significance of this approach is that the requirement of perfect phase matching
      in a single waveguide is no longer necessary, leading to an alternative waveguide
      design for THG. 

PMID- 25768141
TI  - Self-deflecting plasmonic lattice solitons and surface modes in chirped plasmonic
      arrays.
AB  - We show that chirped metal-dielectric waveguide arrays with focusing cubic
      nonlinearity can support plasmonic lattice solitons that undergo self-deflection
      in the transverse plane. Such lattice solitons are deeply subwavelength self
      sustained excitations, although they cover several periods of the array. Upon
      propagation, the excitations accelerate in the transverse plane and follow
      trajectories curved in the direction in which the separation between neighboring
      metallic layers decreases, a phenomenon that yields considerable deflection
      angles. The deflection angle can be controlled by varying the array chirp. We
      also reveal the existence of surface modes at the boundary of truncated plasmonic
      chirped array that form even in the absence of nonlinearity. 

PMID- 25768142
TI  - High-sensitivity ultrashort mid-infrared pulse characterization by modified
      interferometric field autocorrelation.
AB  - We report on spectral phase retrieval of 43 MHz, ~100  fs, 3.3 MUm pulses at
      energies down to 8.9 pJ by a modified interferometric field autocorrelation
      method. The simple setup consists of a Michelson interferometer, a 266 MUm thick
      AgGaSe<sub>2</sub> crystal, and a homemade spectrometer with an InGaAs point
      detector, which is readily applicable to measuring a 20 fs (1.8 cycles) pulse at
      3.3 MUm. The feasibility is verified by comparing with the results obtained by
      simulation and frequency-resolved optical gating for the spectral phase
      modulation because of a 4 mm thick germanium plate. 

PMID- 25768143
TI  - Optical levitation of a microdroplet containing a single quantum dot.
AB  - We demonstrate the optical levitation or trapping in helium gas of a single
      quantum dot (QD) within a liquid droplet. Bright single photon emission from the
      levitated QD in the droplet was observed for more than 200 s. The observed photon
      count rates are consistent with the value theoretically estimated from the two
      photon-action cross section. This Letter presents the realization of an optically
      levitated solid-state quantum emitter. 

PMID- 25768145
TI  - Experimental investigation of chirp properties induced by signal amplification in
      quantum-dot semiconductor optical amplifiers.
AB  - We experimentally show the dynamic frequency chirp properties induced by signal
      amplification in a quantum-dot semiconductor optical amplifier (QD-SOA) for the
      first time. We also compare the red and blue chirp peak values and temporal chirp
      changes while changing the gain and injected signal powers of the QD-SOA with
      those of a common SOA. 

PMID- 25768144
TI  - Simultaneous photoacoustic microscopy of microvascular anatomy, oxygen
      saturation, and blood flow.
AB  - Capitalizing on the optical absorption of hemoglobin, photoacoustic microscopy
      (PAM) is uniquely capable of anatomical and functional characterization of the
      intact microcirculation in vivo. However, PAM of the metabolic rate of oxygen
      (MRO<sub>2</sub>) at the microscopic level remains an unmet challenge, mainly due
      to the inability to simultaneously quantify microvascular diameter, oxygen
      saturation of hemoglobin (sO<sub>2</sub>), and blood flow at the same spatial
      scale. To fill this technical gap, we have developed a multi-parametric PAM
      platform. By analyzing both the sO<sub>2</sub>-encoded spectral dependence and
      the flow-induced temporal decorrelation of photoacoustic signals generated by the
      raster-scanned mouse ear vasculature, we demonstrated-for the first time
      simultaneous wide-field PAM of all three parameters down to the capillary level
      in vivo. 

PMID- 25768146
TI  - Resolving transient time profile in ToF imaging via log-sum sparse
      regularization.
AB  - Multi-frequency time-of-flight (ToF) cameras have been used to recover the
      transient time profiles of optical responses such that multipath interference can
      be separated. The resolution of the recovered time profiles is limited by the
      highest modulation frequency. Here, we demonstrate a method based on log-sum
      sparsity regularization to recover transient time profiles of specular
      reflections. We show that it improves the ability of separating pulses better
      than the state-of-the-art regularization methods. As an application, we
      demonstrate the encoding and decoding of hidden images using mirror reflections. 

PMID- 25768147
TI  - Nonclassical correlations between terahertz-bandwidth photons mediated by
      rotational quanta in hydrogen molecules.
AB  - Quantum photonics offers much promise for the development of new technologies.
      The ability to control the interaction of light and matter at the level of single
      quantum excitations is a prerequisite for the construction of potentially
      powerful devices. Here we use the rotational levels of a room temperature
      ensemble of hydrogen molecules to couple two distinct optical modes at the single
      photon level using femtosecond pulses with 2 THz bandwidth. We observe photon
      correlations that violate a Cauchy-Schwarz inequality, thereby verifying the
      creation of a nonclassical state. This work demonstrates the rich potential of
      molecules for use in ultrafast quantum photonic devices. 

PMID- 25768148
TI  - Implementation of transformed lenses in bed of nails reducing refractive index
      maximum value and sub-unity regions.
AB  - Transformation optics with quasi-conformal mapping is applied to design a
      Generalized Maxwell Fish-eye Lens (GMFEL) which can be used as a power splitter.
      The flattened focal line obtained as a result of the transformation allows the
      lens to adapt to planar antenna feeding systems. Moreover, sub-unity refraction
      index regions are reduced because of the space compression effect of the
      transformation, reducing the negative impact of removing those regions when
      implementing the lens. A technique to reduce the maximum value of the refractive
      index is presented to compensate for its increase because of the transformation.
      Finally, the lens is implemented with the bed of nails technology, employing a
      commercial dielectric slab to improve the range of the effective refractive
      index. The lens was simulated with a 3D full-wave simulator to validate the
      design, obtaining an original and feasible power splitter based on a dielectric
      lens. 

PMID- 25768149
TI  - Monolithic diamond Raman laser.
AB  - A monolithic diamond Raman laser is reported. It utilizes a 13-mm radius of
      curvature lens etched onto the diamond surface and dielectric mirror coatings to
      form a stable resonator. The performance is compared to that of a monolithic
      diamond Raman laser operating in a plane-plane cavity. On pumping with a compact
      Q-switched laser at 532 nm (16 MUJ pulse energy; 1.5 ns pulse duration; 10 kHz
      repetition-rate; M<sup>2</sup><1.5), laser action was observed at the first,
      second, and third Stokes wavelengths (573 nm, 620 nm and 676 nm, respectively) in
      both cases. For the microlens cavity, a conversion efficiency of 84% was achieved
      from the pump to the total Raman output power, with a slope efficiency of 88%.
      This compares to a conversion efficiency of 59% and a slope efficiency of 74% for
      the plane-plane case. Total Raman output powers of 134 and 96 mW were achieved
      for the microlens and plane-plane cavities, respectively. 

PMID- 25768150
TI  - Triple-layer Fabry-Perot/SPP aluminum absorber in the visible and near-infrared
      region.
AB  - We report a theoretical study on a novel type of absorber that can achieve near
      perfect absorption in the visible and near-infrared regions by utilizing the
      Fabry-Perot and the surface plasmon polariton (SPP) effects. The absorber
      consists of an Al/dielectric/Al triple-layered structure with the top Al layer
      consisting of an array of holes. The absorption features can be easily controlled
      by tuning the structural parameters, particularly the porous features of the top
      Al layer. When the porous features in the top Al layer are significantly smaller
      than the wavelength, light absorption is enabled through the Fabry-Perot effect.
      On the other hand, when the porous features in the top layer are at the
      subwavelength scale, new absorption peaks emerge due to the SPP effect.
      Furthermore, when the top Al layer consists of an array of hollow rings, the
      electric field at the interface between the top Al layer and the middle
      dielectric layer is greatly enhanced due to the plasmonic effect, indicating that
      the absorber reported here may be suitable for novel applications, e.g., the
      surface-enhanced Raman spectroscopy (SERS) substrates. 

PMID- 25768151
TI  - Infrared upconversion hyperspectral imaging.
AB  - In this Letter, hyperspectral imaging in the mid-IR spectral region is
      demonstrated based on nonlinear frequency upconversion and subsequent imaging
      using a standard Si-based CCD camera. A series of upconverted images are acquired
      with different phase match conditions for the nonlinear frequency conversion
      process. From this, a sequence of monochromatic images in the 3.2-3.4 MUm range
      is generated. The imaged object consists of a standard United States Air Force
      resolution target combined with a polystyrene film, resulting in the presence of
      both spatial and spectral information in the infrared image. 

PMID- 25768152
TI  - Digital image frequency spectrum method for analyzing speckle displacement in
      frequency domain.
AB  - A technique called the digital image frequency spectrum (DIFS) method, used for
      analyzing digital speckle patterns with deformations in the frequency domain, is
      proposed. Two subimages in the same position as two digital speckle patterns
      before and after deformation are used to form a Young's fringe. The parallel
      Young's fringe pattern is automatically analyzed in the frequency domain. One
      finds that the displacement between the two subimages can be directly obtained,
      and a matching procedure used in digital image correlation (DIC) is unnecessary
      when DIFS is applied. Experimental results show that the relative error of this
      method is less than 3%, and it takes less time in computing integer-pixel
      displacement procedure. 

PMID- 25768153
TI  - Time-stretch high-speed microscopic imaging system based on temporally and
      spectrally shaped amplified spontaneous emission.
AB  - In this Letter, a time-stretch high-speed microscopic imaging system based on
      temporally and spectrally shaped amplified spontaneous emission (ASE) is proposed
      and experimentally demonstrated. We significantly reduced the complexity and cost
      of the light source by applying ASE in the time-stretch microscopic imaging
      system. Furthermore, by slicing and preprocessing the spectrum of the ASE with a
      Fabry-Perot (F-P) filter, the random intensity vibration of the ASE can be
      significantly suppressed, which would notably simplify the image recovery process
      afterward. The resolution of the proposed system is better than 35 MUm and the
      effective 1D scan rate could reach 50 MHz. 

PMID- 25768154
TI  - Active phase-nulling of the self-mixing phase in a terahertz frequency quantum
      cascade laser.
AB  - We demonstrate an active phase-nulling scheme for terahertz (THz) frequency
      quantum cascade lasers (QCLs) under optical feedback, by active electronic
      feedback control of the emission frequency. Using this scheme, the frequency
      tuning rate of a THz QCL is characterized, with significantly reduced
      experimental complexity compared to alternative approaches. Furthermore, we
      demonstrate real-time displacement sensing of targets, overcoming the resolution
      limits imposed by quantization in previously implemented fringe-counting methods.
      Our approach is readily applicable to high-frequency vibrometry and surface
      profiling of targets, as well as frequency-stabilization schemes for THz QCLs. 

PMID- 25768155
TI  - Integral decomposition and polarization properties of depolarizing Mueller
      matrices.
AB  - We show that, by suitably defining the integral decomposition of a depolarizing
      Mueller matrix, it becomes possible to fully interpret the polarization response
      of the medium or structure under study in terms of mean values and variances
      covariances of a set of six integral polarization properties. The latter appear
      as natural counterparts of the elementary (differential) polarization properties
      stemming from the differential decomposition of the Mueller matrix. However,
      unlike the differential decomposition, the integral one is always mathematically
      and physically realizable and is furthermore unambiguously defined inasmuch as a
      nondepolarizing estimate of the initial Mueller matrix is secured. The
      theoretical results are illustrated on an experimental example. 

PMID- 25768156
TI  - Watt-level, gigahertz-linewidth difference-frequency generation in PPLN pumped by
      an nanosecond-pulse fiber laser source.
AB  - We obtained >1  W average power and up to 5 MUJ pulse energy at ~3520  nm
      wavelength via difference-frequency generation (DFG) of an all-fiber, few-ns
      pulse, variable pulse-repetition-frequency laser source operating at 1064 nm and
      10 mW, continuous-wave, 1525 nm single-frequency diode laser, within a 5 cm-long
      periodically poled lithium niobate (PPLN) crystal. To the best of our knowledge,
      this result amounts to the highest-average-power, spectrally bright mid-infrared
      radiation obtained via DFG. 

PMID- 25768157
TI  - Experimental measurements of the origin of self-phasing in passively coupled
      fiber lasers.
AB  - We have directly measured the intensity distribution, gain, and induced phase
      shift between two fiber lasers that are coherently combined by a Dammann grating.
      The induced phase shift between the lasers has been shown to approximately cancel
      out any applied phase error introduced into the cavity, allowing the combined
      resonator to operate at an efficient low-loss state. We show that the origin of
      this self-phasing stems from a redistribution of power between the two lasers.
      The resulting difference in circulating intensity produces a differential change
      in saturated gain, which in turn produces a differential Kramers-Kronig phase
      shift that effectively cancels the applied phase error. 

PMID- 25768158
TI  - Relative carrier-envelope phase stabilization of hybridly synchronized ultrafast
      Yb and Er fiber-laser systems with the feed-forward scheme.
AB  - Stabilization of the relative carrier-envelope (CE) phase for hybridly
      synchronized two-color fs Yb and Er fiber-laser systems is demonstrated for the
      first time by utilizing the feed-forward scheme based on an acousto-optic
      frequency shifter. The slow drift issues arising from the feed-forward scheme are
      solved by adding the in-loop relative CE frequency coarse stabilization via
      modulating the laser pump current. Sub-fs timing locking between the two-color
      pulses is still maintained due to the fast response and large locking range of
      hybrid synchronization. The approach provides an alternative way to obtain phase
      stable synchronized two-color pulses with higher pulse energies. 

PMID- 25768159
TI  - Quantitative imaging of microvasculature in deep tissue with a spectrum-based
      photo-acoustic microscopy.
AB  - We analyze photo-acoustic signals from capillaries and theoretically demonstrate
      the quantitative relationship between vascular diameter and spectral slope in a
      low-frequency band. Phantom experiments validate the theoretical analysis. Based
      on this finding, spectral slope is proposed as the imaging parameter of a photo
      acoustic microscopy. This system effectively quantifies the microvasculature with
      diameters of 60 and 150 MUm, which are smaller than the wavelength 342 MUm at the
      central frequency 4.39 MHz of ultrasound transducer. The low frequency also
      guarantees the imaging depth in the order of centimeters. The proposed scheme
      could be potential for noninvasive diagnosis of diseases related to abnormal
      vasoconstriction or angiectasis. 

PMID- 25768160
TI  - Multioctave, 3-18  MUm sub-two-cycle supercontinua from self-compressing, self
      focusing soliton transients in a solid.
AB  - Strongly coupled nonlinear spatiotemporal dynamics of ultrashort mid-infrared
      pulses undergoing self-focusing simultaneously with soliton self-compression in
      an anomalously dispersive, highly nonlinear solid semiconductor is shown to
      enable the generation of multioctave supercontinua with spectra spanning the
      entire mid-infrared range and compressible to subcycle pulse widths. With 7.9
      MUm, 150 fs, 2 MUJ, 1 kHz pulses used as a driver, 1.2 cycle pulses of mid
      infrared supercontinuum radiation with a spectrum spanning the range of
      wavelengths from 3 to 18 MUm were generated in a 5 mm GaAs plate. Further
      compression of these pulses to subcycle pulse widths is possible through
      compensation of the residual phase shift. 

PMID- 25768161
TI  - Coupling between surface plasmon polaritons and transverse electric polarized
      light via L-shaped nano-apertures.
AB  - Given that plasmonic fields are intrinsically transverse magnetic (TM), coupling
      surface plasmon polaritons (SPPs) and transverse electric (TE) polarized light,
      especially at nanoscale, remain challenging. We propose the use of L-shaped nano
      apertures to overcome this fundamental limitation and enable coupling between
      SPPs and TE polarized light. Polarization conversion originates from the
      interference of two resonant modes excited in the nano-apertures and the nearly
      180 degrees  phase retardation between them. The experiments show that both TE-to
      plasmon and plasmon-to-TE couplings can be implemented at the subwavelength
      scale. This discovery provides great freedom when manipulating light based on
      SPPs at the nanoscale and helps in using the energy of TE polarized light. 

PMID- 25768162
TI  - Anisotropy analysis of third-harmonic generation in a germanium-doped silica
      optical fiber.
AB  - We performed an intermodal third-harmonic generation around 516 nm in a germanium
      doped silica optical fiber. The analysis of the complex polarization behavior
      that was observed allowed us to determine the orientation symmetry group of the
      fiber and the relative values of the independent coefficients of the third-order
      electric susceptibility tensor. 

PMID- 25768163
TI  - Designing directional cloaks from localized fields.
AB  - Designs of cloaking devices and more general invisible objects have primarily
      applied the techniques of transformation optics and scattering cancellation to
      derive material structures that achieve the desired effects. In this Letter, we
      note that it is also possible to construct a broader class of invisible objects
      directly from the defining wave equation. The technique is demonstrated in a
      scalar formalism with illustrative examples. 

PMID- 25768164
TI  - Enhanced lasing assisted by the Ag-encapsulated Au plasmonic nanorods.
AB  - Threshold reduction and emission enhancement were reported for the waveguided
      random lasing, assisted by the Ag-encapsulated Au nanorods (Au@Ag NRs). The blend
      of tris(8-hydroxyquinolinato)aluminum (Alq<sub>3</sub>) and 4-(dicyanomethylene)
      2-tert-butyl-6(1,1,7,7-tetramethyljulolidyl-9-enyl)-4 H-pyran (DCJTB), which
      comprise the typical donor-acceptor lasing system, is used as the gain media.
      Compared with the Ag nanoparticles and Au nanorods, Au@Ag NRs exhibited the broad
      absorption spectra of localized surface plasmon resonance (LSPR) with multiple
      peaks, which sufficiently overlapped with both absorption and emission spectra of
      the donor-acceptor system of the gain media. This unique plasmonic characteristic
      of Au@Ag NRs leads to the lower lasing threshold and enhances the lasing
      efficiency by the effects of both enhancement of localized electromagnetic field
      and scattering. 

PMID- 25768165
TI  - Three-dimensional terahertz imaging using swept-frequency feedback interferometry
      with a quantum cascade laser.
AB  - We demonstrate coherent three-dimensional terahertz imaging by frequency
      modulation of a quantum cascade laser in a compact and experimentally simple self
      mixing scheme. Through this approach, we can realize significantly faster
      acquisition rates compared to previous schemes employing longitudinal mechanical
      scanning of a sample. We achieve a depth resolution of better than 0.1 MUm with a
      power noise spectral density below -50  dB/Hz, for a sampling time of 10 
      ms/pixel. 

PMID- 25768166
TI  - 40-Gb/s PDM-QPSK signal transmission over 160-m wireless distance at W-band.
AB  - We experimentally demonstrate a W-band optical-wireless transmission system over
      160-m wireless distance with a bit rate up to 40 Gb/s. The optical-wireless
      transmission system adopts optical polarization-division-multiplexing (PDM),
      multiple-input multiple-output (MIMO) reception and antenna polarization
      diversity. Using this system, we experimentally demonstrate the 2*2 MIMO wireless
      delivery of 20- and 40-Gb/s PDM quadrature-phase-shift-keying (PDM-QPSK) signals
      over 640- and 160-m wireless links, respectively. The bit-error ratios (BERs) of
      these transmission systems are both less than the forward-error-correction (FEC)
      threshold of 3.8*10<sup>-3</sup>. 

PMID- 25768167
TI  - Ptychographic ultrafast pulse reconstruction.
AB  - We demonstrate a new ultrafast pulse reconstruction modality that is somewhat
      reminiscent of frequency-resolved optical gating but uses a modified setup and a
      conceptually different reconstruction algorithm that is derived from
      ptychography. Even though it is a second-order correlation scheme, it shows no
      time ambiguity. Moreover, the number of spectra to record is considerably smaller
      than in most other related schemes which, together with a robust algorithm, leads
      to extremely fast convergence of the reconstruction. 

PMID- 25768168
TI  - Directional out-coupling of light from a plasmonic nanowire-nanoparticle
      junction.
AB  - We experimentally show how a single Ag nanoparticle (NP) coupled to an Ag
      nanowire (NW) can convert propagating surface plasmon polaritons to directional
      photons. By employing dual-excitation Fourier microscopy with spatially filtered
      collection-optics, we show single- and dual-directional out-coupling of light
      from NW-NP junction for plasmons excited through glass-substrate and air
      superstrate. Furthermore, we show NW-NP junction can influence the directionality
      of molecular-fluorescence emission, thus functioning as an optical antenna. The
      results discussed herein may have implications in realizing directional single
      photon sources and quantum plasmon circuitry. 

PMID- 25768169
TI  - Analysis of anisotropic epsilon-near-zero hetero-junction lens for concentration
      and beam splitting.
AB  - In this Letter, we analyze a recently reported hetero-junction lens of two
      anisotropic epsilon-near-zero (ENZ) media for its concentration and beam
      splitting properties. The equivalent lensmakers' equation of the concentrating
      mechanism is first derived using geometrical optics and dispersion relations; and
      aberrations are discussed. It is shown that the light concentrator's focal
      distance is directly proportional to the thickness of the lens, opposite to
      conventional dielectric lenses. It is then shown that the same hetero-junction
      structure can be used as a near-field beam-splitter when illuminated from the
      back, in addition to its concentration property. Equal and unequal beam
      splitting, as well as beam shifting can be achieved using a very thin device. 

PMID- 25768170
TI  - Stable and high-power few cycle supercontinuum for 2D ultrabroadband electronic
      spectroscopy.
AB  - Broadband supercontinuum (SC) pulses in the few cycle regime are a promising
      source for spectroscopic and imaging applications. However, SC sources are
      plagued by poor stability, greatly limiting their utility in phase-resolved
      nonlinear experiments such as 2D photon echo spectroscopy (2D PES). Here, we
      generated SC by two-stage filamentation in argon and air starting from 100 fs
      input pulses, which are sufficiently high-power and stable to record time
      resolved 2D PE spectra in a single laser shot. We obtain a total power of 400
      MUJ/pulse in the visible spectral range of 500-850 nm and, after compression,
      yield pulses with duration of 6 fs according to transient-grating frequency
      resolved optical gating (TG-FROG) measurements. We demonstrate the method on the
      laser dye, Cresyl Violet, and observe coherent oscillations indicative of nuclear
      wavepacket dynamics. 

PMID- 25768171
TI  - Incident-polarization-sensitive and large in-plane-photonic-spin-splitting at the
      Brewster angle.
AB  - In this Letter, we report a phenomenon of large in-plane-photonic-spin-splitting
      (IPPSS) in the case of a linear polarized Gaussian light beam reflected from an
      air-glass interface at the Brewster angle. The IPPSS-induced displacement reaches
      ~12.4  MUm, which is quite larger than the previously reported value.
      Particularly, the IPPSS is extremely sensitive (~70  MUm/deg) to the incident
      polarization. We also find that the direction of the spin accumulation can be
      switched by adjusting the incident polarization slightly. These findings may have
      useful applications in spin manipulation and precise polarization metrology. 

PMID- 25768172
TI  - Optically controlled low-power on-off mode resonant tunneling oscillator with a
      heterojunction phototransistor switch.
AB  - We report an optically controlled low-power on-off mode oscillator based on a
      resonant tunneling diode (RTD) that is monolithically integrated with a
      heterojunction phototransistor (HPT) optical switch. In order to achieve a low
      power operation at a wavelength of 1.55 MUm an InP-based quantum-effect tunneling
      diode is used for microwave signal generation based on a unique negative
      differential conductance (NDC) characteristic of the RTD at a low applied
      voltage. In addition, the high-gain HPT is used for converting incident optical
      data to an electrical data signal. The fabricated on-off mode oscillator shows a
      low-power consumption of 5 mW and a high-data-rate of 1  Gb/s at an oscillation
      frequency of 4.7 GHz. A good energy efficiency of 5  pJ/bit has been obtained due
      to the low DC power consumption along with high-data-rate performance of the RTD
      based optoelectronic integration scheme. 

PMID- 25768173
TI  - Generation of three-octave-spanning transient Raman comb in hydrogen-filled
      hollow-core PCF.
AB  - A noise-seeded transient comb of Raman sidebands spanning three octaves from 180
      to 2400 nm, is generated by pumping a hydrogen-filled hollow-core photonic
      crystal fiber with 26-MUJ, 300-fs pulses at 800 nm. The pump pulses are
      spectrally broadened by both Kerr and Raman-related self-phase modulation (SPM),
      and the broadening is then transferred to the Raman lines. In spite of the high
      intensity, and in contrast to bulk gas-cell based experiments, neither SPM
      broadening nor ionization are detrimental to comb formation. 

PMID- 25768174
TI  - Eyesafe coherent detection wind lidar based on a beam-combined pulsed laser
      source.
AB  - We report on a coherent wind lidar built with two coherently-beam-combined fiber
      amplifiers. The lidar performances of the combined-amplifier and the single
      amplifier are compared using two criterions: carrier-to-noise ratio and wind
      speed noise floor. In both cases, lidar performances are not degraded with a
      combined source and are close to the theoretical optimum. Combined sources are
      well suited to improve coherent wind lidar accuracy, range, and integration time.

PMID- 25768175
TI  - Volcanic CO2 detection with a DFM/OPA-based lidar.
AB  - The DFM/OPA-based lidar BILLI was used to investigate the volcanic plume released
      by the hydrothermal vent of Pisciarelli, in the Campi Flegrei volcano. BILLI
      remotely measured CO<sub>2</sub> concentrations in cross-sections of the near
      vent plume using the differential absorption technique. To our knowledge, this is
      the first example of lidar-based measurement of volcanic CO<sub>2</sub>. The
      spatial resolution was 1.5 m and the temporal resolution 20 s. 

PMID- 25768176
TI  - Composite multi-vortex diffraction-free beams and van-Hove singularities in
      honeycomb lattices.
AB  - We find diffraction-free beams for graphene and MoS<sub>2</sub>-type honeycomb
      optical lattices. The resulting composite solutions have the form of multi
      vortices, with spinor topological charges (n, n+/-1). Exact solutions for the
      spinor components are obtained in the Dirac limit. The effects of the valley
      degree of freedom and the mass are analyzed. Passing through the van Hove
      singularity, the topological structure of the solutions is modified. Exactly at
      the singularity, the diffraction-free beams take the form of strongly localized
      one-dimensional stripes. 

PMID- 25768177
TI  - Designing photonic crystal waveguides for broadband four-wave mixing
      applications.
AB  - We present photonic crystal waveguide designs which exhibit large four-wave
      mixing efficiencies over a wide wavelength region. These designs are identified
      using an optimization process taking into account sophisticated figure-of-merits
      that depend on the pump bandwidth and the signal/pump tunability. The obtained
      designs achieve up to -18.9  dB conversion efficiency, tunable over a 10 nm
      tunability range. We also present alternative designs that are less efficient but
      have smaller power requirements and are far more compact. 

PMID- 25768178
TI  - Stabilization of spatiotemporal solitons in Kerr media by dispersive coupling.
AB  - We introduce a mechanism to stabilize spatiotemporal solitons in Kerr nonlinear
      media, based on the dispersion of linear coupling between the field components
      forming the soliton states. Specifically, we consider solitons in a two-core
      guiding structure with inter-core coupling dispersion (CD). We show that CD
      profoundly affects properties of the solitons, causing the complete stabilization
      of the otherwise highly unstable spatiotemporal solitons in Kerr media with
      focusing nonlinearity. We also find that the presence of CD stimulates the
      formation of bound states, which, however, are unstable. 

PMID- 25768179
TI  - Differential-pressure-based fiber-optic temperature sensor using Fabry-Perot
      interferometry.
AB  - We propose a novel fiber-optic Fabry-Perot interferometric (FFPI) temperature
      sensor based on differential pressure resulting from thermal expansion of sealed
      air. A thin silicon diaphragm is sandwiched between two micro-circular cavity
      structured Pyrex plates to construct a FP and an air cavity. The thermal
      expansion of sealed air induces differential pressure variation between cavities
      and thus the deformation of thin diaphragm, which transfers temperature change
      into cavity length shift of FP interferometer. Theory analysis results indicate
      that the temperature-sensitivity can be designed flexibly by choosing the
      parameters of radius and thickness of silicon diaphragm, and the differential
      pressure between two cavities. Experimental results demonstrate that the
      temperature sensitivity of 6.07 nm/ degrees C is achieved with the resolution of
      0.10 degrees C under the range of -50 degrees C to 100 degrees C, and the
      response time is around 1.3 s with temperature change from 28 degrees C to 100
      degrees C. 

PMID- 25768180
TI  - Finite-difference complex-wavevector band structure solver for analysis and
      design of periodic radiative microphotonic structures.
AB  - We demonstrate a finite-difference approach to complex-wavevector band structure
      simulation and its use as a tool for the analysis and design of periodic leaky
      wave photonic devices. With the (usually real) operating frequency and unit-cell
      refractive index distribution as inputs, the eigenvalue problem yields the
      complex-wavevector eigenvalues and Bloch modes of the simulated structure. In a
      two-dimensional implementation for transverse-electric fields with radiation
      accounted for by perfectly matched layer boundaries, we validate the method and
      demonstrate its use in simulating the complex-wavevector band structures and
      modal properties of a silicon photonic crystal waveguide, an array-antenna
      inspired grating coupler with unidirectional radiation, and a recently
      demonstrated low-loss Bloch-mode-based waveguide crossing array. Additionally, we
      show the first direct solution of the recently proposed open-system low-loss
      Bloch modes. We expect this method to be a valuable tool in photonics design,
      enabling the rigorous analysis and synthesis of advanced periodic and quasi
      periodic photonic devices. 

PMID- 25768181
TI  - Creation of a three-dimensional spherical fluorescence spot for super-resolution
      microscopy using a two-color annular hybrid wave plate.
AB  - We fabricate a two-color annular hybrid wave plate (TAHWP) for fluorescence
      depletion super-resolution microscopy by combining quartz plates. Inserting the
      TAHWP into a commercial laser-scanning microscope together with a quarter-wave
      plate creates a three-dimensional spherical fluorescence spot smaller than the
      diffraction limit. Since a simple experimental setup easily provides a spot with
      a volume of ~100  nm<sup>3</sup>, the TAHWP can improve the performance of
      various microspectroscopic devices. 

PMID- 25768182
TI  - Ultra-compact resonant tunneling-based TE-pass and TM-pass polarizers for SOI
      platform.
AB  - We investigate the polarization-dependent resonance tunneling effect in silicon
      waveguides to achieve ultra-compact and highly efficient polarization fitters for
      integrated silicon photonics, to the best of our knowledge for the first time. We
      hence propose simple structures for silicon-on-insulator transverse electric (TE)
      pass and transverse magnetic (TM)-pass polarizers based on the resonance
      tunneling effect in silicon waveguides. The suggested TE-pass polarizer has
      insertion losses (IL), extinction ratio (ER), and return losses (RL) of 0.004 dB,
      18 dB, and 24 dB, respectively; whereas, the TM-pass polarizer is characterized
      by IL, ER, and RL of 0.15 dB, 20 dB, and 23 dB, respectively. Both polarizers
      have an ultra-short device length of only 1.35 and 1.31 MUm for the TE-pass and
      the TM-pass polarizers which are the shortest reported lengths to the best of our
      knowledge. 

PMID- 25768183
TI  - Harmonic mode locking of bound solitons.
AB  - We systematically investigate the passive harmonic mode locking (HML) of the
      bound states of two solitons in a fiber laser that has been mode locked by
      nonlinear polarization rotation (NPR). The experiment shows that the stable HML
      state of the bound solitons (BSs) with a fixed and discrete separation is
      obtained. The repetition rate changes by increasing the pump power and slightly
      altering the polarization state in the cavity. The dynamic is similar to the HML
      of a single-pulse operation. In our experiment, the repetition rate can be turned
      from the fundamental mode locking up to ninth-order HML when the pump power is
      increased from 168 to 476.1 mW. Once the BSs are obtained, their separation is
      fixed at 1.5 ps, regardless of the HML order. Under the direct BS interaction,
      the BS trains are very stable and easily reproducible. This HML behavior of BSs
      confirms that the BS is another intrinsic feature of the laser, except for the
      single soliton. 

PMID- 25768184
TI  - Three-octave-spanning supercontinuum generation and sub-two-cycle self
      compression of mid-infrared filaments in dielectrics.
AB  - We experimentally and numerically investigate the spectral and temporal structure
      of mid-infrared (mid-IR) filaments in bulk dielectrics with normal and anomalous
      group velocity dispersion (GVD) pumped by a 2.1 MUm optical parametric chirped
      pulse amplifier (OPCPA). The formation of stable and robust filaments with
      several microjoules of pulse energy is observed. We demonstrate a supercontinuum
      that spans more than three octaves from ZnS in the normal GVD regime and self
      compression of the mid-IR pulse to sub-two-cycle duration in CaF<sub>2</sub> in
      the anomalous GVD regime. The experimental observations quantitatively agree well
      with the numerical simulations based on a three-dimensional nonlinear wave
      equation that reveals the detailed spatio-temporal dynamics of mid-IR filaments
      in dielectrics. 

PMID- 25768185
TI  - Second-harmonic generation at 532 nm in K(3)B(6)O(10)Br crystal.
AB  - We demonstrate that an average power of 45.5 W at 532 nm is obtained with a 13 mm
      length K<sub>3</sub>B<sub>6</sub>O<sub>10</sub>Br (KBB) crystal corresponding to
      a conversion efficiency of 36.5% for the first time. The power stability of the
      532 nm output power measurement indicates that the standard deviation jitters of
      the average power are 1.46% and 1.50% at 24.8 and 43.8 W, respectively. The
      effective nonlinear optical coefficient d<sub>eff</sub> is also obtained as 0.92
      pm/V by the phase-matching (PM) method. The angle and temperature bandwidths of
      second-harmonic generation (SHG) for 1064 nm pump light are also investigated.
      Therefore, KBB crystal can be a promising nonlinear optical material for visible
      laser generation. 

PMID- 25768186
TI  - High-efficiency photon capturing in ultrathin silicon solar cells with front
      nanobowl texture and truncated-nanopyramid reflector.
AB  - We present a crystalline siliconthin-film (5 MUm) solar cell decorated by a front
      nanobowled texture and a rear truncated-nanopyramid silver reflector. This design
      substantially suppresses the overall light reflection and enhances the optical
      resonances inside the silicon film leading to the photon-capturing performance
      comparable to the Yablonovitch limit. We show that optical absorption can be
      greatly improved by adjusting the ratio of the periods between the rear and front
      nanostructures with an optimal ultimate photocurrent density around 35.3 
      mA/cm<sup>2</sup> and an enhancement of 42.6% relative to the planar counterpart.
      A thorough optoelectronic simulation predicts the light-conversion efficiency of
      around 15.5%, i.e., 67.3% higher than that of the planar system. 

PMID- 25768187
TI  - 1.8-10  MUm mid-infrared supercontinuum generated in a step-index chalcogenide
      fiber using low peak pump power.
AB  - By pumping an 11-cm-long step-index chalcogenide fiber with ~330  fs pulses at
      4.0 MUm from an optical parametric amplifier, mid-infrared supercontinuum
      generation spanning from ~1.8 to ~10  MUm within a dynamic range of +/-15  dB has
      been demonstrated at a relatively low power threshold of ~3000  W. 

PMID- 25768188
TI  - Generation of a widely tunable linearly chirped microwave waveform based on
      spectral filtering and unbalanced dispersion.
AB  - We propose a method to generate a widely tunable linearly chirped microwave
      waveform based on spectral filtering and unbalanced dispersion. Heterodyne
      beating between two differently dispersed optical pulses in a photodetector
      produces the linearly chirped microwave waveform. Desired waveforms with flexible
      and independent control of the center frequency and sweep bandwidth can be
      obtained by simply tuning two optical filters. Simulation and experimental
      investigations are carried out, and the results are in good agreement. The
      measured microwave waveform has ~5.2-ns pulse duration and ~64-GHz sweep
      bandwidth, corresponding to a time-bandwidth product of ~166.4 and a compression
      ratio of ~248. 

PMID- 25768189
TI  - Diffraction grating three-beam interferometry without self-imaging regime
      contrast modulations.
AB  - Achromatic grating shearing interferometry method for wave front sensing is
      developed. Two Fresnel diffraction patterns formed by grating three lowest
      diffraction orders are recorded. The beam-splitter grating is displaced laterally
      by half its period between exposures. Calculating the sum of two patterns results
      in a two-beam interferogram free of inherent light propagation direction and
      observation plane contrast modulations imposed by the self-imaging phenomenon
      (Talbot effect). Single-frame automatic fringe pattern processing provides the
      interferogram phase distribution. The technique enables continuous shear
      variations suitable for dynamic range sensing. Experimental works corroborate
      enhanced capabilities of the proposed approach. 

PMID- 25768190
TI  - Experimental observations of spectral changes produced by individual microscopic
      spheres.
AB  - Spectral changes in individual micrometer-sized scatters are experimentally
      measured. Using an interferometric microscope equipped with a wavelength-swept
      illumination, the optical fields diffracted from the individual scatters are
      measured precisely, from which 2D light scattering spectra were retrieved as
      functions of the wavelength and scattering angle. In the measured scattering
      spectra of individual scatters, spectral shifts were clearly observed, which is
      also directly explained using the Mie scattering theory. 

PMID- 25768191
TI  - Direct generation of 2  W average-power and 232  nJ picosecond pulses from an
      ultra-simple Yb-doped double-clad fiber laser.
AB  - We report the generation of 2.06 W average-power and 232 nJ picosecond mode
      locked pulses directly from an ultra-simple Yb-doped fiber laser. A section of Yb
      doped double-clad fiber pumped by a 976 nm laser diode provides the large gain,
      and the linear cavity is simply formed by a 1064 nm highly reflective fiber Bragg
      grating and a fiber loop mirror (FLM) using a 5/95 optical coupler. The
      asymmetric FLM not only acts as the output mirror for providing ~20% optical
      feedback, but also equivalently behaves as a nonlinear optical loop mirror (NOLM)
      to initiate the mode-locking operation in this cavity. Stable mode-locking is
      therefore achieved over a pump power of 3.76 W. The mode-locked pulses show the
      dissipative soliton resonance (DSR), which has the pulse duration of 695 ps to ~1
      ns, and the almost unchanged peak power of ~200  W as increasing the pump power.
      In particular, this laser can emit 232 nJ high-energy DSR pulses with an average
      output power of >2  W. This is, to the best of our knowledge, the first
      demonstration of such an ultra-simple, mode-locked fiber laser that enables watt
      level, high energy, picosecond DSR pulses. 

PMID- 25768192
TI  - 6.5 W ZnGeP(2) OPO directly pumped by a Q-switched Tm(3+)-doped single-oscillator
      fiber laser.
AB  - An efficient actively Q-switched Tm<sup>3+</sup>-doped single-oscillator fiber
      laser based on a silica polarization-maintaining (PM) double-clad fiber provided
      average powers of 23 W at pulse widths of 65 ns at 40 kHz pulse repetition
      frequency. It was used to directly pump a ZnGeP<sub>2</sub> optical parametric
      oscillator (OPO). Up to 6.5 W were generated in mid-IR wavelength range. 

PMID- 25768193
TI  - Elegant Cartesian Laguerre-Hermite-Gaussian laser cavity modes.
AB  - In this work, we present a new family of modes of confocal resonators
      eigenfunctions of the Fraunhofer diffraction integral, the elegant Cartesian
      Laguerre-Hermite-Gaussian modes. We show that these modes can be single-pass or
      round-trip eigenmodes of the resonator depending on the focal distance of the
      mirrors and their separation. We study their properties and compare them to the
      well known normal and elegant Hermite and Laguerre-Gauss modes of laser
      resonators. The new family of modes are not structurally stable on propagation as
      normal Gaussian modes nor present a monotonic intensity evolution as the normal
      and elegant Gaussian modes. We also demonstrate that on propagation, they present
      the self-healing property. 

PMID- 25768194
TI  - Distinguishing nonlinear processes in atomic media via orbital angular momentum
      transfer.
AB  - We suggest a technique based on the transfer of topological charge from applied
      laser radiation to directional and coherent optical fields generated in ladder
      type excited atomic media to identify the major processes responsible for their
      appearance. As an illustration, in Rb vapors, we analyze transverse intensity and
      phase profiles of the forward-directed collimated blue and near-IR light using
      self-interference and astigmatic transformation techniques when either or both of
      two resonant laser beams carry orbital angular momentum. Our observations
      unambiguously demonstrate that emission at 1.37 MUm is the result of a parametric
      four-wave mixing process involving only one of the two applied laser fields. 

PMID- 25768196
TI  - Fractional Schrodinger equation in optics.
AB  - In quantum mechanics, the space-fractional Schrodinger equation provides a
      natural extension of the standard Schrodinger equation when the Brownian
      trajectories in Feynman path integrals are replaced by Levy flights. Here an
      optical realization of the fractional Schrodinger equation, based on transverse
      light dynamics in aspherical optical cavities, is proposed. As an example, a
      laser implementation of the fractional quantum harmonic oscillator is presented
      in which dual Airy beams can be selectively generated under off-axis longitudinal
      pumping. 

PMID- 25768195
TI  - Assessing microstructures of the cornea with Gabor-domain optical coherence
      microscopy: pathway for corneal physiology and diseases.
AB  - Gabor-domain optical coherence microscopy (GD-OCM) was applied ex vivo in the
      investigation of corneal cells and their surrounding microstructures with
      particular attention to the corneal endothelium. Experiments using fresh pig
      eyeballs, excised human corneal buttons from patients with Fuchs' endothelial
      dystrophy (FED), and healthy donor corneas were conducted. Results show in a
      large field of view (1  mm*1  mm) high definition images of the different cell
      types and their surrounding microstructures through the full corneal thickness at
      both the central and peripheral locations of porcine corneas. Particularly, an
      image of the endothelial cells lining the bottom of the cornea is highlighted. As
      compared to healthy human corneas, the corneas of individuals with FED show
      characteristic microstructural alterations of the Descemet's membrane and
      increased size and number of keratocytes. The GD-OCM-based imaging system
      developed may constitute a novel tool for corneal imaging and disease diagnosis.
      Also, importantly, it may provide insights into the mechanism of corneal
      physiology and pathology, particularly in diseases of the corneal endothelium. 

PMID- 25768197
TI  - Continuous-variable entanglement measurement using an unbalanced Mach-Zehnder
      interferometer.
AB  - We propose a simple scheme using an unbalanced Mach-Zehnder interferometer to
      directly measure the entangled beams with correlation of amplitude quadratures
      and anticorrelation of phase quadratures. In the experiment, we use two fibers
      with lengths of 2 and 50 m to construct the interferometer. The correlation
      variances of amplitude difference and phase sum of the entangled beams from a
      nondegenerate optical parametric amplifier are simultaneously measured to be 1.79
      and 1.62 dB below the shot noise limit, respectively. Such a simple and
      convenient method has potential applications in quantum measurements. 

PMID- 25768198
TI  - Temporal imaging with squeezed light.
AB  - We generalize the scheme of conventional temporal imaging to quantum temporal
      imaging viable for nonclassical states of light. As an example, we apply our
      scheme to temporally broadband squeezed light and demonstrate a possibility of
      its noiseless magnification. In particular, we show that one can magnify by a
      given factor the coherence time of squeezed light and match it to the response
      time of the photodetector. This feature opens new possibilities for practical
      applications of temporally broadband squeezed light in quantum optics and quantum
      information. 

PMID- 25768199
TI  - Reconfigurable non-blocking four-port optical router based on microring
      resonators.
AB  - A reconfigurable non-blocking four-port optical router with the least optical
      switches is demonstrated. The device is based on microring resonators tuned
      through thermo-optic effect. The optical signal-to-noise ratio of the device at
      its nine routing states is about 15 dB. A 25 Gbps data transmission has been
      performed on its whole 12 optical links, and 8-channel wavelength division
      multiplexing data transmission has been implemented to expand its communication
      capacity. The energy efficiency of the device is 23 fJ/bit, and the response time
      of the device is about 25 MUs. 

PMID- 25768200
TI  - Coexistence of three-wave, four-wave, and five-wave mixing processes in a
      superconducting artificial atom.
AB  - We present a theoretical study of multiwave mixing in a driven superconducting
      quantum qubit (artificial atom) with a cyclic Xi-type three-level structure. We
      first show that three-wave mixing (3WM), four-wave mixing (4WM), and five-wave
      mixing (5WM) processes can coexist in the microwave regime in such an artificial
      system due to the absence of selection rules. Because of electromagnetically
      induced transparency suppression of linear absorption in a standard Xi-type
      configuration, the generated 4WM is enhanced greatly and its efficiency can be as
      high as 0.1% for only a single artificial atom. We also show that Autler-Townes
      splitting occurs in the 3WM and 5WM spectra and quantum interference has a
      significant impact on the total signal intensity being a coherent superposition
      of these two signals. 

PMID- 25768201
TI  - Sodium periodate mediated oxidative transformations in organic synthesis.
AB  - The investigation of new oxidative transformations for the synthesis of carbon
      heteroatom and heteroatom-heteroatom bonds is of fundamental importance in the
      synthesis of numerous bioactive molecules and fine chemicals. In this context,
      NaIO4, an exciting reagent, has attracted increasing attention enabling the
      development of these unprecedented oxidative transformations that are difficult
      to achieve otherwise. Thus, NaIO4 has been successfully explored as a versatile
      oxidant for a variety of fundamental organic transformations such as C-H
      activation, oxidative functionalization of alkenes and other interesting
      oxidative transformations and its application in the synthesis of bioactive
      natural products. This review summarizes recent developments in this area with
      NaIO4 as a versatile oxidant and brings out many challenges that still remain
      elusive for the future. 

PMID- 25768202
TI  - Macrophage motility is driven by frontal-towing with a force magnitude dependent
      on substrate stiffness.
AB  - The ability of macrophages to properly migrate is crucial to their success as
      early responders during the innate immune response. Furthermore, improper
      regulation of macrophage migration is known to contribute to several pathologies.
      The signaling mechanisms underlying macrophage migration have been previously
      studied but to date the mechanical mechanism of macrophage migration has not been
      determined. In this study, we have created the first traction maps of motile
      primary human macrophages by observing their migration on compliant
      polyacrylamide gels. We find that the force generated by migrating macrophages is
      concentrated in the leading edge of the cell - so-called frontal towing - and
      that the magnitude of this force is dependent on the stiffness of the underlying
      matrix. With the aid of chemical inhibitors, we show that signaling through the
      RhoA kinase ROCK, myosin II, and PI3K is essential for proper macrophage force
      generation. Finally, we show that Rac activation by its GEF Vav1 is crucial for
      macrophage force generation while activation through its GEF Tiam1 is
      unnecessary. 

PMID- 25768203
TI  - Synthesis of polyhydroxylated piperidine and pyrrolidine peptidomimetics via one
      pot sequential lactam reduction/Joullie-Ugi reaction.
AB  - A direct approach to the synthesis of polyhydroxylated piperidine and pyrrolidine
      peptidomimetics is described. The presented strategy is based on one-pot
      reduction of sugar-derived lactams with Schwartz's reagent followed by a
      multicomponent Ugi-Joullie reaction. 

PMID- 25768205
TI  - Stereocontrolled Formation of Several Carbon-Carbon Bonds in Acyclic Systems.

PMID- 25768206
TI  - Structures and energetics of (MgCO3)n clusters (n <= 16).
AB  - There is significant interest in the role of carbonate minerals for the storage
      of CO2 and the role of prenucleation clusters in their formation. Global minima
      for (MgCO3)n (n <= 16) structures were optimized using a tree growth-hybrid
      genetic algorithm in conjunction with MNDO/MNDO/d semiempirical molecular orbital
      calculations followed by density functional theory geometry optimizations with
      the B3LYP functional. The most stable isomers for (MgCO3)n (n < 5) are
      approximately 2-dimensional. Mg can be bonded to one or two O atoms of a CO3(2-),
      and the 1-O bonding scheme is more favored as the cluster becomes larger. The
      average C-Mg coordination number increases as the cluster size increases, and at
      n = 16, the average C-Mg coordination number was calculated to be 5.2. The
      normalized dissociation energy to form monomers increases as n increases. At n =
      16, the normalized dissociation energy is calculated to be 116.2 kcal/mol, as
      compared to the bulk value of 153.9 kcal/mol. The adiabatic reaction energies for
      the recombination reactions of (MgO)n clusters and CO2 to form (MgCO3)n were
      calculated. The exothermicity of the normalized recombination energy ?RE?CO2
      decreases as n increases and converged to the experimental bulk limit rapidly.
      The normalized recombination energy ?RE?CO2 was calculated to be -52.2 kcal/mol
      for the monomer and -30.7 kcal/mol for n = 16, as compared to the experimental
      value of -27.9 kcal/mol for the solid phase reaction. Infrared spectra for the
      lowest energy isomers were calculated, and absorption bands in the previous
      experimental infrared studies were assigned with our density functional theory
      predictions. The (13)C, (17)O, and (25) Mg NMR chemical shifts for the clusters
      were predicted. The results provide insights into the structural and energetic
      transitions from nanoclusters of (MgCO3)n to the bulk and the spectroscopic
      properties of clusters for their experimental identification. 

PMID- 25768204
TI  - Nanopore detection of 8-oxoguanine in the human telomere repeat sequence.
AB  - The human telomere repeat sequence 5'-TTAGGG-3' is a hot spot for oxidation at
      guanine, yielding 8-oxo-7,8-dihydroguanine (OG), a biomarker of oxidative stress.
      Telomere shortening resulting from oxidation will ultimately induce cellular
      senescence. In this study, alpha-hemolysin (alpha-HL) nanopore technology was
      applied to detect and quantify OG in the human telomeric DNA sequence. This
      repeat sequence adopts a basket G-quadruplex in the NaCl electrolyte used for
      analysis that enters the alpha-HL channel, slowly unfolds, and translocates. The
      basket fold containing OG disrupts the structure, leading to >10* increase in the
      unfolding kinetics without yielding a detectable current pattern. Therefore,
      detection of OG with alpha-HL required labeling of OG with aminomethyl-[18-crown
      6] using a mild oxidant. The labeled OG yielded a pulse-like signal in the
      current vs time trace when the DNA strand was electrophoretically passed through
      alpha-HL in NaCl electrolyte. However, the rate of translocation was too slow
      using NaCl salts, leading us to further refine the method. A mixture of NH4Cl and
      LiCl electrolytes induced the propeller fold that unravels quickly outside the
      alpha-HL channel. This electrolyte allowed observation of the labeled OG, while
      providing a faster recording of the currents. Lastly, OG distributions were
      probed with this method in a 120-mer stretch of the human telomere sequence
      exposed to the cellular oxidant (1)O2. Single-molecule profiles determined the OG
      distributions to be random in this context. Application of the method in
      nanomedicine can potentially address many questions surrounding oxidative stress
      and telomere attrition observed in various disease phenotypes including prostate
      cancer and diabetes. 

PMID- 25768207
TI  - [Repair of post-hysterectomy vesicovaginal fistulae: the state of the art].
AB  - In western countries, vesicovaginal fistulae (VVF) are mostly iatrogenic and in
      the majority of cases are secondary to hysterectomy. The golden standard for the
      treatment of VVF has remained largely unchanged since 1953 (Couvelaire): good
      visualization, good dissection, good approximation of the margins, and good urine
      drainage. However, several aspects are still being debated, including whether or
      not to pursue conservative repair, the timing for surgical repair, whether to
      perform excision of the fistula tract, the best type of surgical access, and
      whether or not to use tissue interposition. We decided to review the state of the
      art in the treatment of VVF, which are exclusively of a traumatic nature and non
      radiated, by performing a bibliography search carried on Pubmed using keywords
      such as "vesicovaginal fistula". The search focused on recent articles and was
      largely restricted to the past 10 years.

PMID- 25768208
TI  - A rapid method for tetrodotoxin (TTX) determination by LC-MS/MS from small
      volumes of human serum, and confirmation of pufferfish poisoning by TTX
      monitoring.
AB  - A simple and rapid detection method for tetrodotoxin (TTX), a powerful sodium
      channel blocker, in small volumes of the serum of patients with pufferfish
      poisoning, was developed using an ultrafiltration spin column. The separation and
      identification of TTX was performed by liquid chromatography (LC) with a multi
      mode ODS column and tandem mass spectrometry. TTX and an internal standard
      (voglibose) were monitored and quantitated using ion transitions: the respective
      precursor-to-product ion combinations, m/z 320/162 for TTX and 268/92 in MRM
      mode. The recoveries of TTX and voglibose were 91.0-110.8% and 104.7-107.4%,
      respectively, and with high accuracy (intra-run, 4.35-5.29%; inter-run, 2.95
      5.79%) and linearity (0.5-200 ng/ml serum: r = 0.9994). The lower limit of
      quantification was 0.5 ng/ml serum. In patients, maximum serum TTX concentrations
      were 30.2 ng/ml serum for patient 1 on day 0 and 56.1 ng/ml serum for patient 2
      on day 1. These results are important for the treatment of patients and for the
      identification of poisoning as well as for the determination of the cause of the
      food poisoning.

PMID- 25768210
TI  - Analysis of effects of climate change on runoff in an urban drainage system: a
      case study from Seoul, Korea.
AB  - Both water quantity and quality are impacted by climate change. In addition,
      rapid urbanization has also brought an immeasurable loss of life and property
      resulting from floods. Hence, there is a need to predict changes in rainfall
      events to effectively design stormwater infrastructure to protect urban areas
      from disaster. This study develops a framework for predicting future short
      duration rainfall intensity and examining the effects of climate change on urban
      runoff in the Gunja Drainage Basin. Non-stationarities in rainfall records are
      first analysed using trend analysis to extrapolate future climate change
      scenarios. The US Environmental Protection Agency Storm Water Management Model
      (SWMM) was used for single event simulation of runoff quantity from the study
      area. For the 1-hour and 24-hour durations, statistically significant upward
      trends were observed. Although the 10-minute duration was only nearly significant
      at the 90% level, the steepest slope was observed for this short duration.
      Moreover, it was observed that the simulated peak discharge from SWMM increases
      as the short duration rainfall intensity increases. The proposed framework is
      thought to provide a means to review the current design of stormwater
      infrastructures to determine their capacity, along with consideration of climate
      change impact. 

PMID- 25768211
TI  - Lead sorption performance on active silica derived from fly ash.
AB  - The object of this study was to estimate the sorption property of active silica
      derived from fly ash after separation of silica and aluminum. The specific
      surface area of active silica enlarged to 115 m(2)/g was compared with the
      original fly ash (4 m(2)/g). Field emission scanning electron microscopy
      displayed the active silica, which looked like a honeycomb or curly layer with
      many lamellae that formed many mesopores. The uptake kinetics indicated that the
      residual concentration of Pb(2+) in the aqueous solution decreased rapidly from
      the initial 1.25 mg/L to less than 10 MUg/L within 45 min. The removal efficiency
      of Pb(2+) on active silica was pH dependent. The increase in pH value promoted
      Pb(2+) removal because the negative surface provided more electrostatic
      attraction sites. A stepwise non-linear isotherm was obtained because the
      lamellae of active silica provided a heterogeneous surface with various kinds of
      active sites. The maximum sorption amount of Pb on active silica was more than 90
      mg/g, which was better than some pristine-activated carbon. 

PMID- 25768209
TI  - Persistent Organic Pollutants Modify Gut Microbiota-Host Metabolic Homeostasis in
      Mice Through Aryl Hydrocarbon Receptor Activation.
AB  - BACKGROUND: Alteration of the gut microbiota through diet and environmental
      contaminants may disturb physiological homeostasis, leading to various diseases
      including obesity and type 2 diabetes. Because most exposure to environmentally
      persistent organic pollutants (POPs) occurs through the diet, the host
      gastrointestinal tract and commensal gut microbiota are likely to be exposed to
      POPs. OBJECTIVES: We examined the effect of 2,3,7,8-tetrachlorodibenzofuran
      (TCDF), a persistent environmental contaminant, on gut microbiota and host
      metabolism, and we examined correlations between gut microbiota composition and
      signaling pathways. METHODS: Six-week-old male wild-type and Ahr-/- mice on the
      C57BL/6J background were treated with 24 MUg/kg TCDF in the diet for 5 days. We
      used 16S rRNA gene sequencing, 1H nuclear magnetic resonance (NMR) metabolomics,
      targeted ultra-performance liquid chromatography coupled with triplequadrupole
      mass spectrometry, and biochemical assays to determine the microbiota
      compositions and the physiological and metabolic effects of TCDF. RESULTS:
      Dietary TCDF altered the gut microbiota by shifting the ratio of Firmicutes to
      Bacteroidetes. TCDF-treated mouse cecal contents were enriched with Butyrivibrio
      spp. but depleted in Oscillobacter spp. compared with vehicle-treated mice. These
      changes in the gut microbiota were associated with altered bile acid metabolism.
      Further, dietary TCDF inhibited the farnesoid X receptor (FXR) signaling pathway,
      triggered significant inflammation and host metabolic disorders as a result of
      activation of bacterial fermentation, and altered hepatic lipogenesis,
      gluconeogenesis, and glycogenolysis in an AHR-dependent manner. CONCLUSION: These
      findings provide new insights into the biochemical consequences of TCDF exposure
      involving the alteration of the gut microbiota, modulation of nuclear receptor
      signaling, and disruption of host metabolism.

PMID- 25768212
TI  - Removal of hexavalent chromium from aqueous solutions using micro zero-valent
      iron supported by bentonite layer.
AB  - Hexavalent chromium Cr(VI) is of particular environmental concern due to its
      toxicity, mobility, and challenging removal from industrial wastewater. It is a
      strong oxidizing agent that is carcinogenic and mutagenic and diffuses quickly
      through soil and aquatic environments. Moreover, it does not form insoluble
      compounds in aqueous solutions; therefore, separation by precipitation is not
      feasible. While Cr(VI) oxyanions are very mobile and toxic in the environment,
      trivalent Cr(III) cations are the opposite and, like many metal cations, Cr(III)
      forms insoluble precipitates. Thus, reducing Cr(VI)-Cr(III) simplifies its
      removal from effluent and also reduces its toxicity and mobility. Permeable
      reactive barriers (PRBs) with zero-valent iron (ZVI) have been used to remediate
      contaminated groundwater with metals, but using ZVI in remediation of
      contaminated groundwater or wastewater is limited due to its lack of stability,
      easy aggregation, and difficulty in separation of iron from the treated solution.
      Thus, the technology used in the present study is developed to address these
      problems by placing a layer of bentonite after the PRB layer to remove iron from
      the treated water. The removal rates of Cr(VI) under different values of pH were
      investigated, and the results indicated the highest adsorption capacity at low
      pH. 

PMID- 25768213
TI  - Population dynamics of filamentous bacteria identified in Polish full-scale
      wastewater treatment plants with nutrients removal.
AB  - A comprehensive study of the identity and population dynamics of filamentous
      bacteria in five Polish full-scale municipal wastewater treatment plants (WWTPs)
      with nutrients removal had been carried out for 2 years. A quantitative culture
      independent, molecular method - fluorescence in situ hybridization - was applied
      to evaluate the structure of different filamentous bacteria populations and their
      temporal variations. Activated sludge was examined for the abundance of 11 groups
      of filamentous bacteria. On average, filaments constituted 28% of all bacteria.
      All samples presented a low diversity of probe-defined filamentous bacteria,
      usually with significant domination of Chloroflexi (with distinction to types
      1851, 0803 and others) and/or Microthrix (14% and 7% of EUBmix, respectively).
      Haliscomenobacter hydrossis, Mycolata, Skermania piniformis and TM7 were less
      abundant, whereas Curvibacter, Thiothrix/021N and family Gordonia have not been
      detected in any of the samples. The tested WWTPs showed similarity among species
      found and differences in their abundance. The composition of filamentous
      populations was rather stable in each plant and similar to those found in other
      European countries. Little differences between plants were shown by multivariate
      analysis of variance in terms of Chloroflexi and Microthrix. No significant
      general correlations have been found with Pearson product-moment correlation
      coefficient and Spearman's rank correlation coefficient. Medium correlation
      strength between the presence of different filaments was recorded only for
      Microthrix and Skermania piniformis. Deleterious effect on settling properties of
      sludge (measured as sludge volume index) was found only for abundance of
      Microthrix; a strong linear correlation was recorded between them. However, no
      other correlations with wastewater and operational data were revealed. 

PMID- 25768214
TI  - Development of low-cost rotational rheometer.
AB  - Liquids with non-Newtonian properties are presented in many engineering areas, as
      for example in membrane bioreactors where active sludge exhibits shear thinning
      properties. Therefore, the ability to determine the rheology's dependence on
      shear is important when optimising systems with such liquids. However, rheometers
      capable of determining the viscosity are often expensive and so a cheaper
      alternative is constructed with this exact capability. Using the principle of
      rotating rheometers, a low-cost rheometer was built to determine the rheology of
      Newtonian and non-Newtonian liquids. The general principles and background
      assumptions and the physics are described. The rheometer was calibrated by
      comparison with measurements conducted on a Brookfield viscometer for Newtonian
      liquids. For validation measurements on non-Newtonian liquids, xanthan gum
      solutions were made and compared with measurements on the Brookfield viscometer
      and with values from other sources. Furthermore, the effect of excluding the
      different shear rates in the system is discussed and good practice hereto is
      given. 

PMID- 25768215
TI  - Using hydrological simulation to detect human-disturbed epoch in runoff series.
AB  - Runoff in major rivers in China has been decreasing in recent decades, mainly due
      to climate change and human activity. River basin managers have a critical
      interest in detecting and diagnosing non-stationaries in runoff time series. Here
      we use a rainfall runoff model-based approach to identify the human-disturbed
      periods of the record. The method is applied to the Kuye River catchment, located
      in the Loess Plateau, China. The SimHyd model performs well for simulation of
      monthly natural discharges, and the method suggests that discernable human
      influence began in 1980. Anthropogenic effects were detectable several years
      earlier at the downstream stations than the upstream stations, consistent with
      pace and timing of soil and water conservation measures implemented across the
      Kuye River catchment. 

PMID- 25768216
TI  - Effect of sensor location on controller performance in a wastewater treatment
      plant.
AB  - Complete mixing is hard to achieve in large bioreactors in wastewater treatment
      plants. This often leads to a non-uniform distribution of components such as
      dissolved oxygen and, hence, the process rates depend on them. Furthermore, when
      these components are used as input for a controller, the location of the sensor
      can potentially affect the control action. In this contribution, the effect of
      sensor location and the choice of setpoint on the controller performance were
      examined for a non-homogeneously mixed pilot bioreactor described by a
      compartmental model. The impacts on effluent quality and aeration cost were
      evaluated. It was shown that a dissolved oxygen controller with a fixed setpoint
      performs differently as a function of the location of the sensor. When placed in
      a poorly mixed location, the controller increases the aeration intensity to its
      maximum capacity leading to higher aeration costs. When placed just above the
      aerated zone, the controller decreases the aeration rate resulting in lower
      dissolved oxygen concentrations in the remainder of the system, compromising
      effluent quality. In addition to the location of the sensor, the selection of an
      appropriate setpoint also impacts controller behavior. This suggests that mixing
      behavior of bioreactors should be better quantified for proper sensor location
      and controller design. 

PMID- 25768218
TI  - ATAD control goals through the analysis of process variables and evaluation of
      quality, production and cost.
AB  - The aim of this paper is to establish and quantify different operational goals
      and control strategies in autothermal thermophilic aerobic digestion (ATAD). This
      technology appears as an alternative to conventional sludge digestion systems.
      During the batch-mode reaction, high temperatures promote sludge stabilization
      and pasteurization. The digester temperature is usually the only online, robust,
      measurable variable. The average temperature can be regulated by manipulating
      both the air injection and the sludge retention time. An improved performance of
      diverse biochemical variables can be achieved through proper manipulation of
      these inputs. However, a better quality of treated sludge usually implies major
      operating costs or a lower production rate. Thus, quality, production and cost
      indices are defined to quantify the outcomes of the treatment. Based on these,
      tradeoff control strategies are proposed and illustrated through some examples.
      This paper's results are relevant to guide plant operators, to design automatic
      control systems and to compare or evaluate the control performance on ATAD
      systems. 

PMID- 25768217
TI  - Influence of COD/sulfate ratios on the integrated reactor system for simultaneous
      removal of carbon, sulfur and nitrogen.
AB  - An integrated reactor system was developed for the simultaneous removal of
      carbon, sulfur and nitrogen from sulfate-laden wastewater and for elemental
      sulfur (S degrees ) reclamation. The system mainly consisted of an expanded
      granular sludge bed (EGSB) for sulfate reduction and organic carbon removal (SR
      CR), an EGSB for denitrifying sulfide removal (DSR), a biological aerated filter
      for nitrification and a sedimentation tank for sulfur reclamation. This work
      investigated the influence of chemical oxygen demand (COD)/sulfate ratios on the
      performance of the system. Influent sulfate and ammonium were fixed to the level
      of 600 mg SO(4)(2-) L-1 and 120 mg NH(4)(+) L-1, respectively. Lactate was
      introduced to generate COD/SO(4)(2-) = 0.5:1, 1:1, 1.5:1, 2:1, 3:1, 3.5:1 and
      4:1. The experimental results indicated that sulfate could be efficiently reduced
      in the SR-CR unit when the COD/SO(4)(2-) ratio was between 1:1 and 3:1, and
      sulfate reduction was inhibited by the growth of methanogenic bacteria when the
      COD/SO(4)(2-) ratio was between 3.5:1 and 4:1. Meanwhile, the Org-C/S2-/NO(3)(-)
      ratios affected the S(0) reclamation efficiency in the DSR unit. When the
      influent COD/SO(4)(2-) ratio was between 1:1 and 3:1, appropriate Org-C/S2
      /NO(3)(-) ratios could be achieved to obtain a maximum S degrees  recovery in the
      DSR unit. For the microbial community of the SR-CR unit at different COD/SO(4)(2
      ) ratios, 16S rRNA gene-based high throughput Illumina MiSeq sequencing was used
      to analyze the diversity and potential function of the dominant species.

PMID- 25768219
TI  - Nitrogen removal efficiency and microbial community analysis of ANAMMOX biofilter
      at ambient temperature.
AB  - An upflow anaerobic biofilter (AF) was developed to investigate anaerobic
      ammonium-oxidizing (ANAMMOX) efficiency in treating low-strength wastewater at
      ambient temperature (15.3-23.2  degrees C). Denaturing gradient gel
      electrophoresis (DGGE) and fluorescence in situ hybridization were used to
      investigate treatment effects on the microbial community. Stepwise decreases in
      influent ammonia concentration could help ANAMMOX bacteria selectively acclimate
      to low-ammonia conditions. With an influent ammonia concentration of 46.5 mg/L,
      the AF reactor obtained an average nitrogen removal rate of 2.26 kg/(m3 day), and
      a removal efficiency of 75.9%. polymerase chain reaction-DGGE results showed that
      microbial diversity in the low matrix was greater than in the high matrix.
      Microbial community structures changed when the influent ammonia concentration
      decreased. The genus of functional ANAMMOX bacteria was Candidatus Kuenenia
      stuttgartiensis, which remained stationary across study phases. Visual
      observation revealed that the relative proportions of ANAMMOX bacteria decreased
      from 41.6 to 36.3% across three study phases. The AF bioreactor successfully
      maintained high activity due to the ANAMMOX bacteria adaptation to low
      temperature and substrate conditions.

PMID- 25768220
TI  - Acetic acid recovery from a hybrid biological-hydrothermal treatment process of
      sewage sludge - a pilot plant study.
AB  - A two-stage process consisting of anaerobic fermentation followed by sub-critical
      wet oxidation was used to generate acetic acid from sewage sludge at pilot scale.
      Volatile fatty acids, dominated by propionic acid, were produced over 4-6 days in
      the 2,000 L fermentation reactor, which also achieved 31% solids reduction.
      Approximately 96% of the carbon was retained in solution over the fermentation
      stage. Using a 200 L wet oxidation reactor operating in batch mode, the second
      stage achieved 98% volatile suspended solids (VSS) destruction and 67% total
      chemical oxygen demand (tCOD) destruction. Acetic acid produced in this stage was
      recalcitrant to further degradation and was retained in solution. The gross yield
      from VSS was 16% for acetic acid and 21% for volatile fatty acids across the
      process, higher than reported yields for wet oxidation alone. The pilot plant
      results showed that 72% of the incoming phosphorus was retained in the solids,
      94% of the nitrogen became concentrated in solution and 41% of the carbon was
      converted to a soluble state, in a more degradable form. Acetic acid produced
      from the process has the potential to be used to offset ethanol requirements in
      biological nutrient removal plants. 

PMID- 25768221
TI  - Cake porosity analysis using 1D-3D fractal dimensions in coagulation
      microfiltration of NOM.
AB  - Fouling during coagulation-ceramic microfiltration of natural organic matter was
      investigated. Two process configurations (inline coagulation (IC) and tank
      coagulation (TC)) and two process conditions (types of coagulants-aluminum-based
      PAX and iron-based PIX-and G-values) were studied. The rate of irreversible
      fouling corresponding to the increase of initial transmembrane pressure after
      backwash of IC-PAX was lowest followed by TC-PAX and TC-PIX, while the
      performance of IC-PIX was found worst. The 1D and 2D fractal analysis revealed
      that flocs from IC were morphologically different from those of TC, leading to
      different filtration characteristics. The 3D fractal analysis revealed two groups
      of morphologically similar flocs: one led to successful filtration experiments,
      whereas the other led to unsuccessful ones. Cake porosity was found dependent on
      the floc morphology. Thus, such an approach was found complementary with fouling
      analysis by means of a membrane fouling model and minimization of fouling
      phenomenon was achieved by combining the two approaches. 

PMID- 25768222
TI  - Adsorption of copper on tri-amino-functionalized mesoporous delta manganese
      dioxide from aqueous solution.
AB  - A novel adsorbent, named tri-amino-functionalized mesoporous delta manganese
      dioxide (NNN-MnO2), was synthesized by bonding trimethoxysilyl propyl
      diethylenetriamine onto the surface of delta manganese dioxide (delta-MnO2) and
      used as a Cu(II) adsorbent in aqueous solution. The graft of silane coupling
      agent onto delta-MnO2was verified by Fourier transform infrared spectroscopy. The
      crystalline structure of the adsorbents was indicated by an X-ray powder
      diffractometer. The specific surface area, pore volume, and Barrett-Joyner
      Halenda pore diameter of the NNN-MnO2were 93.50 m2 g(-1), 0.31 cm-1 g-1, and
      13.12 nm, respectively. The Elovich equation described well the Cu(II) adsorbing
      process and the negative values of DeltaG and the positive values of DeltaH and
      DeltaS indicated a spontaneous and endothermic process. The Langmuir equation
      fitted well the adsorption isotherm at 298 K and the maximum adsorption capacity
      of NNN-MnO2for Cu(II) at pH 4 was 87.72 mg g-1, which was higher than that of the
      un-functionalized delta-MnO2(66.67 mg g-1). The graft of tri-amino-functional
      groups enhanced the uptake of Cu(II), and NNN-MnO2was a promising candidate for
      Cu(II) removal from aqueous solution.

PMID- 25768223
TI  - Sequential recovery of copper and nickel from wastewater without net energy
      input.
AB  - A novel bioelectrochemical system (BES) was designed to recover copper and nickel
      from wastewater sequentially. The BES has two chambers separated by a bipolar
      membrane and two cathodes. Firstly, the copper ions were reduced on a graphite
      cathode with electricity output, and then with an additional bias-potential
      applied, the nickel ions were recovered sequentially on a copper sheet with
      electricity input. In this design, nickel and copper can be recovered and
      separated sequentially on two cathodes. By adjusting the molar ratio of copper
      and nickel ions to 2.99:1 in wastewater, 1.40 mmol Cu2+ could be recovered with
      143.78 J electricity outputs, while 50.68 J electricity was input for 0.32 mmol
      nickel reduction. The total energy output of copper recovery was far more than
      the electricity input of nickel reduction. The present technology provides a
      potential method for heavy metal ion separation and recovery.

PMID- 25768224
TI  - Trace organics removal using three membrane bioreactor configurations: MBR, IFAS
      MBR and MBMBR.
AB  - Seventeen pharmaceutically active compounds and 22 other trace organic pollutants
      were analysed regularly in the influent and permeate from a semi-real plant
      treating municipal wastewater. The plant was operated during 29 months with
      different configurations which basically differed in the type of biomass present
      in the system. These processes were the integrated fixed-film activated sludge
      membrane bioreactor (IFAS-MBR), which combined suspended and attached biomass,
      the moving bed membrane bioreactor (MBMBR) (only attached biomass) and the MBR
      (only suspended biomass). Moreover, removal rates were compared to those of the
      wastewater treatment plant (WWTP) operating nearby with conventional activated
      sludge treatment. Reverse osmosis (RO) was used after the pilot plant to improve
      removal rates. The highest elimination was found for the IFAS-MBR, especially for
      hormones (100% removal); this was attributed to the presence of biofilm, which
      may lead to different conditions (aerobic-anoxic-anaerobic) along its profile,
      which increases the degradation possibilities, and also to a higher sludge age of
      the biofilm, which allows complete acclimation to the contaminants. Operating
      conditions played an important role, high mixed liquor suspended solids (MLSS)
      and sludge retention time (SRT) being necessary to achieve these high removal
      rates. Although pharmaceuticals and linear alkylbenzene sulfonates showed high
      removal rates (65-100%), nonylphenols and phthalate could only be removed to 10
      30%. RO significantly increased removal rates to 88% mean removal rate. 

PMID- 25768225
TI  - Pretreatment of piggery wastewater by a stable constructed microbial consortium
      for improving the methane production.
AB  - A stable aerobic microbial consortium, established by successive subcultivation,
      was employed to solubilize the solid organic fraction in swine wastewater. In the
      30 days' successive biological pretreatments, 30-38% of volatile solids and 19
      28% total solids in raw slurry were solubilized after 10 hours at 37  degrees C.
      Meanwhile, soluble chemical oxygen demand (COD) and volatile fatty acid increased
      by 48%-56% and 600%-750%, respectively. Furthermore, the molecular microbial
      profile of the consortium in successive pretreatment was conducted by denaturing
      gradient gel electrophoresis (DGGE). The results indicated that bacterial species
      of the consortium rapidly overgrew the indigenous microbial community of raw
      water, and showed a stable predominance at the long-term treatment. As a
      consequence of biological pretreatment, pretreatment shortened digestion time by
      50% and increased biogas production by 45% compared to raw water in the anaerobic
      process. The microbial consortium constructed herein is a potential candidate
      consortium for biological pretreatment of swine wastewater to enhance biogas
      production. 

PMID- 25768226
TI  - N-methyl-2-pyrrolidone-degrading bacteria from activated sludge.
AB  - N-methyl-2-pyrrolidone (NMP) is a widely used solvent for many organic compounds
      and a component found in a vast array of chemical preparations. For this research
      paper, NMP degrading bacteria were isolated from two samples of activated sludge.
      They pertained to both Gram-negative and Gram-positive members, and belong to the
      Pseudomonas, Paracoccus, Acinetobacter and Rhodococcus genera. All the strains
      utilized 300 mg/L of NMP as the only source of carbon, energy and nitrogen over
      several days, and they were shown to additionally be able to degrade N
      acetylphenylalanine (NAP). The growth of all the isolated strains was recorded at
      different NMP concentrations, to a maximum of 20 g/L. 

PMID- 25768227
TI  - Simultaneous pollutant removal and electricity generation in denitrifying
      microbial fuel cell with boric acid-borate buffer solution.
AB  - A double-chamber denitrifying microbial fuel cell (MFC), using boric acid-borate
      buffer solution as an alternative to phosphate buffer solution, was set up to
      investigate the influence of buffer solution concentration, temperature and
      external resistance on electricity generation and pollutant removal efficiency.
      The result revealed that the denitrifying MFC with boric acid-borate buffer
      solution was successfully started up in 51 days, with a stable cell voltage of
      205.1 +/- 1.96 mV at an external resistance of 50 Omega. Higher concentration of
      buffer solution favored nitrogen removal and electricity generation. The maximum
      power density of 8.27 W/m(3) net cathodic chamber was obtained at a buffer
      solution concentration of 100 mmol/L. An increase in temperature benefitted
      electricity generation and nitrogen removal. A suitable temperature for this
      denitrifying MFC was suggested to be 25  degrees C. Decreasing the external
      resistance favored nitrogen removal and organic matter consumption by
      exoelectrogens. 

PMID- 25768228
TI  - Fenton oxidation of gallic and p-coumaric acids in water assisted by an activated
      carbon cloth.
AB  - The objective of this study was to investigate the effect of the presence of an
      activated carbon cloth (ACC) during the degradation and removal of gallic acid
      (GA) and p-coumaric acid (pCA) by Fenton oxidation using H2O2 and FeSO4 as
      catalyst. Removal of GA or pCA by Fenton oxidation was much higher than that of
      total organic carbon (TOC), indicating that a large proportion of GA or pCA
      degradation products was not mineralized. The presence of ACC increased the
      concentration of hydroxyl radicals generated in the FeSO4 + H2O2 system. The
      presence of ACC during Fenton oxidation largely increased TOC and GA removal,
      attributable to the adsorption of GA and its degradation products and the
      increased generation of OH(*) radicals that mineralize them. In the Fenton
      oxidation of pCA, the presence of ACC produced the same effects as for GA, but
      now the increased removal of pCA was due to adsorption on the activated carbon
      and not to the increased generation of hydroxyl radicals, due to the greater
      affinity of pCA for the carbon surface and its more difficult mineralization in
      comparison to GA. 

PMID- 25768229
TI  - Ammonia sanitization of blackwater for safe use as fertilizer.
AB  - Source-separated blackwater from low-flush toilets contains plant-available
      nutrients and can be used as a fertilizer. The aim of the study was to evaluate
      the impact on pathogen inactivation when treating blackwater with urea and/or
      lime. Blackwater was spiked with Salmonella typhimurium, Escherichia coli O157,
      Enterococcus faecalis, and Ascaris suum eggs, and treated with urea and/or lime
      in concentrations up to 0.1% w/w. The bottles were kept in a storage facility
      (manure slurry tank) for 102 days while monitoring the pathogen concentrations.
      The treatment time needed to meet the requirement for Salmonella and E. coli
      reduction could be reduced at least six-fold. The enterococci were more
      persistent, and only the highest treatment doses had a significantly higher
      inactivation than the controls. The Ascaris egg viability was only reduced by
      around 50%, so higher urea/lime doses and/or longer treatment times are required
      to fulfill the treatment requirements of 3 log10 reductions of parasite eggs. 

PMID- 25768230
TI  - Arteriovenous fistula stent infection diagnosed with radiolabelled leucocyte
      scintigraphy.
AB  - Infectious complications of haemodialysis in patients with arteriovenous fistula
      stent are rare. In addition, patients with low-grade infection are more difficult
      to diagnose. Here, we report the first case of low-grade infection of an
      arteriovenous fistula stent diagnosed using (99m)Tc-hexamethylpropylene amine
      oxime (HMPAO)-labelled leucocyte scintigraphy. A 62-year-old man with end-stage
      renal disease was referred for prolonged fever. We performed (99m)Tc-HMPAO
      labelled leucocyte scintigraphy following a work-up according to fever of unknown
      origin. A focal uptake on the left forearm compatible with the arteriovenous
      fistula stent insertion site was shown, and the stent was removed. (99m)Tc-HMPAO
      labelled leucocyte scintigraphy could be a suitable method for assessing vascular
      stent infection in low-grade fever. 

PMID- 25768231
TI  - VIM- and IMP-type metallo-beta-lactamase-producing Shigella spp. in childhood
      diarrhea from Andaman Islands.

PMID- 25768233
TI  - Living in history and living by the cultural life script: How older Germans date
      their autobiographical memories.
AB  - This study examines predictions from two theories on the organisation of
      autobiographical memory: Cultural Life Script Theory which conceptualises the
      organisation of autobiographical memory by cultural schemata, and Transition
      Theory which proposes that people organise their memories in relation to personal
      events that changed the fabric of their daily lives, or in relation to negative
      collective public transitions, called the Living-in-History effect. Predictions
      from both theories were tested in forty-eight-old Germans from Berlin and
      Northern Germany. We tested whether the Living-in-History effect exists for both
      negative (the Second World War) and positive (Fall of Berlin Wall) collectively
      experienced events, and whether cultural life script events serve as a prominent
      strategy to date personal memories. Results showed a powerful, long-lasting
      Living-in History effect for the negative, but not the positive event. Berlin
      participants dated 26% of their memories in relation to the Second World War.
      Supporting cultural life script theory, life script events were frequently used
      to date personal memories. This provides evidence that people use a combination
      of culturally transmitted knowledge and knowledge based on personal experience to
      navigate through their autobiographical memories, and that experiencing war has a
      lasting impact on the organisation of autobiographical memories across the life
      span. 

PMID- 25768232
TI  - Empathy and motivation for justice: Cognitive empathy and concern, but not
      emotional empathy, predict sensitivity to injustice for others.
AB  - Why do people tend to care for upholding principles of justice? This study
      examined the association between individual differences in the affective,
      motivational and cognitive components of empathy, sensitivity to justice, and
      psychopathy in participants (N 265) who were also asked to rate the
      permissibility of everyday moral situations that pit personal benefit against
      moral standards of justice. Counter to common sense, emotional empathy was not
      associated with sensitivity to injustice for others. Rather, individual
      differences in cognitive empathy and empathic concern predicted sensitivity to
      justice for others, as well as the endorsement of moral rules. Psychopathy
      coldheartedness scores were inversely associated with motivation for justice.
      Moreover, hierarchical multiple linear regression analysis revealed that self
      focused and other-focused orientations toward justice had opposing influences on
      the permissibility of moral judgments. High scores on psychopathy were associated
      with less moral condemnation of immoral behavior. Together, these results
      contribute to a better understanding of the information processing mechanisms
      underlying justice motivation, and may guide interventions designed to foster
      justice and moral behavior. In order to promote justice motivation, it may be
      more effective to encourage perspective taking and reasoning than emphasizing
      emotional sharing with the misfortune of others. 

PMID- 25768234
TI  - Preface.

PMID- 25768235
TI  - Modeling alternate RNA structures in genomic sequences.
AB  - We introduce the concept of RNA multistructures, which is a formal grammar-based
      framework specifically designed to model a set of alternate RNA secondary
      structures. Such alternate structures can either be a set of suboptimal foldings,
      or distinct stable folding states, or variants within an RNA family. We provide
      several such examples and propose an efficient algorithm to search for RNA
      multistructures within a genomic sequence. 

PMID- 25768236
TI  - Chaining sequence/structure seeds for computing RNA similarity.
AB  - We describe a new method to compare a query RNA with a static set of target RNAs.
      Our method is based on (i) a static indexing of the sequence/structure seeds of
      the target RNAs; (ii) searching the target RNAs by detecting seeds of the query
      present in the target, chaining these seeds in promising candidate homologs; and
      then (iii) completing the alignment using an anchor-based exact alignment
      algorithm. We apply our method on the benchmark Bralibase2.1 and compare its
      accuracy and efficiency with the exact method LocARNA and its recent seeds-based
      speed-up ExpLoc-P. Our pipeline RNA-unchained greatly improves computation time
      of LocARNA and is comparable to the one of ExpLoc-P, while improving the overall
      accuracy of the final alignments. 

PMID- 25768237
TI  - Metastatic Tumor Volume and Extranodal Tumor Extension: Clinical Significance in
      Patients With Stage II Breast Cancer.
AB  - CONTEXT: Lymph node status and the number of lymph node (LN) positive for cancer
      cells are the most important prognostic factors in breast cancer. Extranodal
      tumor extension (ENTE) has been used as a histopathologic feature to classify
      patients into high risk versus low risk for local recurrence. However, in the
      current era of early detection and systemic therapy, the prognostic significance
      of ENTE is not as well defined in patients with 1 to 3 LNs positive for cancer.
      OBJECTIVE: To determine whether the amount of tumor burden in an axillary
      dissection or the presence of ENTE provides any additional information regarding
      patient outcome in patents with 1 to 3 positive LN results. DESIGN: Clinical and
      pathologic factors were identified for 456 patients with breast cancer at the
      University of Texas MD Anderson Cancer Center, Houston, who had pT1 tumors and 1
      to 3 LNs positive for cancer and were treated by mastectomy, with or without
      postmastectomy radiotherapy, between 1978 and 2007. RESULTS: Of the 456 patients,
      257 (56.4%), 141 (31.6%), and 58 (12.7%) patients had 1, 2, or 3 positive LN
      results, respectively. Extranodal tumor extension was present in 99 patients
      (21.7%) and was absent in the remaining 357 cases (78.3%). Seventy-six patients
      (16.7%) received radiation therapy. Patients had both worse overall survival time
      and disease-free survival when ENTE was present, regardless of the amount, as
      long as the treatment era was not included in the multivariate analysis (pre-2000
      versus post-2000). However, ENTE was no longer significant on multivariate
      analysis when the year of treatment was taken into account. CONCLUSIONS: The
      number of positive LNs remains an important predictor of survival in patients
      with 1 to 3 positive LN results, but the prognostic significance of ENTE in this
      cohort of patients has diminished over time.

PMID- 25768238
TI  - Comparison of preoperative oral acetazolamide and intraperitoneal normal saline
      irrigation for reduction of postoperative pain after laparoscopic
      cholecystectomy.
AB  - PURPOSE: Visceral and shoulder tip pain following laparoscopic cholecystectomy is
      mainly due to carbon dioxide (CO2) insufflation. Various methods have been
      adopted to eliminate residual CO2. We compared the postoperative analgesic
      efficacy of intraperitoneal normal saline (30 mL/kg) irrigation with preoperative
      oral acetazolamide administration in patients undergoing laparoscopic
      cholecystectomy. MATERIALS AND METHODS: Sixty patients between 20 and 60 years of
      age were included in this prospective, randomized, double-blind study. Patients
      in Group I received placebo, Group II patients received preoperative oral
      acetazolamide (5 mg/kg), and Group III patients received intraperitoneal
      irrigation with 30 mL/kg of normal saline. Intravenous paracetamol (1 g) was
      administered every 6 hours for postoperative analgesia. Parietal and visceral
      pain scores at rest, on movement, and on coughing and shoulder tip pain were
      recorded using a visual analog scale after arrival in the postanesthesia care
      unit, at 1, 2, 4, 6, 12, and 24 hours after surgery. Rescue analgesia was
      provided with an intravenous fentanyl (1 MUg/kg) bolus whenever the visual analog
      scale score was >=4. RESULTS: Compared with Group I, Group III patients had
      significantly lower visceral pain scores at all time intervals except at 12
      hours. Group III patients also recorded significantly lower visceral pain scores
      than Group II from 2 to 24 hours. There was no significant difference in shoulder
      tip pain. The total dose of fentanyl used was significantly less in Group III.
      CONCLUSIONS: Intraperitoneal normal saline irrigation is more effective than
      acetazolamide in reducing postoperative visceral pain after laparoscopic
      cholecystectomy and has significant opioid-sparing effect. However, its effect on
      shoulder pain is comparable to that of acetazolamide.

PMID- 25768239
TI  - Cognitive functioning and walking speed in older adults as predictors of
      limitations in self-reported instrumental activity of daily living: prospective
      findings from the Obu Study of Health Promotion for the Elderly.
AB  - Our aim was to determine whether baseline measures of cognitive functioning,
      walking speed, and depressive status are independent predictors of limitations in
      instrumental activities of daily living (IADL) in older adults. The cross
      sectional study involved 1329 community-dwelling adults, aged 75 years or older.
      At baseline, the Mini-Mental State Examination (MMSE), Symbol Digit Substitution
      Test (SDST), Geriatric Depressive Scale (GDS), and a word list memory task were
      completed, and self-reported IADLs and walking speed were recorded. The
      longitudinal study involved 948 participants without baseline IADL limitation,
      which was assessed at baseline and 15-month follow up, using the three Kihon
      Checklist subitems. In cross-sectional analyses, participants with IADL
      limitation demonstrated greater GDS scores, slower walking speeds, and lower
      MMSE, word list memory task, and SDST (only for women) scores relative to those
      without IADL limitation. In the longitudinal analyses, baseline walking speed
      (men: OR 0.98; women: OR 0.97, p<0.05) and word list memory task scores (men: OR
      0.84; women: OR 0.83, p<0.05) in both sexes and SDST scores in women (OR 0.96,
      p=0.04) were independent predictors of subsequent IADL limitation. Walking speed,
      memory, and processing speed may be independent predictors of IADL limitation in
      older adults.

PMID- 25768240
TI  - Characterization of aminoglycoside resistance and virulence genes among
      Enterococcus spp. isolated from a hospital in China.
AB  - This study investigated the aminoglycoside resistance phenotypes and genotypes,
      as well as the prevalence of virulence genes, in Enterococcus species isolated
      from clinical patients in China. A total of 160 enterococcal isolates from
      various clinical samples collected from September 2013 to July 2014 were
      identified to the species level using the VITEK-2 COMPACT system. The
      antimicrobial susceptibilities of the identified Enterococcus strains were
      determined by the Kirby-Bauer (K-B) disc diffusion method. PCR-based assays were
      used to detect the aminoglycoside resistance and virulence genes in all
      enterococcal isolates. Of 160 Enterococcus isolates, 105 were identified as E.
      faecium, 35 as E. faecalis, and 20 isolates were classified as "other"
      Enterococcus species. High-level aminoglycoside resistance (HLAR) for gentamicin,
      streptomycin, and both antibiotics was identified in 58.8, 50, and 34.4% of
      strains, respectively. The most common virulence gene (50.6% of isolates) was
      efaA, followed by asa1 (28.8%). The most prevalent aminoglycoside resistance
      genes were aac(6')-Ie-aph(2''), aph(2')-Id, aph(3')-IIIa, and ant(6')-Ia, present
      in 49.4%, 1.3%, 48.8% and 31.3% of strains, respectively. Overall, E. faecium and
      E. faecalis were most frequently associated with hospital-acquired enterococcal
      infections in Zhejiang Province. All aminoglycoside resistance genes, except
      aph(2'')-Id, were significantly more prevalent in HLAR strains than amongst high
      level aminoglycoside susceptible (HLAS) strains, while there was no significant
      difference between HLAR and HLAS strains in regard to the prevalence of virulence
      genes, apart from esp, therefore, measures should be taken to manage infections
      caused by multi-drug resistant Enterococcus species. 

PMID- 25768241
TI  - Methicillin-resistant Staphylococcus aureus (MRSA) contamination in bedside
      surfaces of a hospital ward and the potential effectiveness of enhanced
      disinfection with an antimicrobial polymer surfactant.
AB  - The aim in this study was to assess the effectiveness of a quaternary ammonium
      chloride (QAC) surfactant in reducing surface staphylococcal contamination in a
      routinely operating medical ward occupied by patients who had tested positive for
      methicillin-resistant Staphylococcus aureus (MRSA). The QAC being tested is an
      antibacterial film that is sprayed onto a surface and can remain active for up to
      8 h. A field experimental study was designed with the QAC plus daily hypochlorite
      cleaning as the experimental group and hypochlorite cleaning alone as the control
      group. The method of swabbing on moistened surfaces was used for sampling. It was
      found that 83% and 77% of the bedside surfaces of MRSA-positive and MRSA-negative
      patients respectively were contaminated with staphylococci at 08:00 hours, and
      that the staphylococcal concentrations increased by 80% at 1200 h over a 4-hour
      period with routine ward and clinical activities. Irrespective of the MRSA status
      of the patients, high-touch surfaces around the bed-units within the studied
      medical ward were heavily contaminated (ranged 1 to 276 cfu/cm2 amongst the sites
      with positive culture) with staphylococcal bacteria including MRSA, despite the
      implementation of daily hypochlorite wiping. However, the contamination rate
      dropped significantly from 78% to 11% after the application of the QAC polymer.
      In the experimental group, the mean staphylococcal concentration of bedside
      surfaces was significantly (p<0.0001) reduced from 4.4+/-8.7 cfu/cm2 at 08:00
      hours to 0.07+/-0.26 cfu/cm2 at 12:00 hours by the QAC polymer. The results of
      this study support the view that, in addition to hypochlorite wiping, the tested
      QAC surfactant is a potential environmental decontamination strategy for
      preventing the transmission of clinically important pathogens in medical wards.

PMID- 25768242
TI  - South African foundation phase teachers' perceptions of ADHD at private and
      public schools.
AB  - This study investigated foundation phase teachers' perceptions of Attention
      Deficit Hyperactivity Disorder (ADHD). The teachers' views on the aetiology,
      appropriate interventions and incidence rates of ADHD were examined. A total of
      130 foundation phase teachers from mainstream private and public schools
      completed a self-developed questionnaire that had been piloted by the
      researchers. Both descriptive and inferential statistics were used to analyse the
      data, specifically to determine whether there were differences in responses
      between public and private school teachers. Thematic content analysis was used to
      identify the themes that emerged from the open-ended questions. It was found that
      the teachers had a limited understanding of ADHD, in terms of what it is as well
      as the aetiology. In addition, it emerged that medication was the preferred
      method of intervention despite the participants' awareness of alternative
      intervention methods. A comparison of the private and public school teachers'
      results indicated no significant difference in their perceptions regarding the
      aetiology, interventions or incidence rates of ADHD. 

PMID- 25768243
TI  - Lower AMP-activated protein kinase level is associated with the vulnerability of
      coronary atherosclerotic plaques by attenuating the expression of monocyte
      autophagy.
AB  - BACKGROUND: Coronary atherosclerotic plaque formation is driven by macrophage
      infiltration. Monocytes and macrophages contribute to the progression of
      atherosclerosis. However, research on the relationship between AMP-activated
      protein kinase (AMPK) and vulnerable atherosclerotic plaques is still
      insufficient. In the present study, we aimed to elucidate the adaptive mechanism
      between autophagy of peripheral blood monocytes (PBMs) and the rupture of
      atherosclerotic plaques. We investigated whether AMPK and autophagy of monocytes
      can enhance the stability of coronary atherosclerotic plaques in the human body.
      PATIENTS AND METHODS: Samples of PBMs were collected and isolated from all
      patients with stable angina pectoris (SAP), non-ST-segment elevation acute
      coronary syndrome, ST-segment elevation acute myocardial infarction, and without
      coronary artery disease (control). Then, western blot was used to detect the
      expression levels of AMPK and autophagy-related protein. RESULTS: The expression
      levels of beclin-1 and ATG7 were all significantly lower in the acute coronary
      syndrome groups than those in the SAP and control groups (all P<0.01). The level
      of phosphorylated AMPK was significantly decreased in patients with acute
      coronary syndrome compared with those in the SAP and control groups (P<0.01).
      However, there was no statistical difference between the SAP group and the
      control group. The activation of mTOR was distinctly increased in the STEMI group
      (P<0.05). CONCLUSION: Therefore, our work is novel in showing that AMPK of PBMs
      may decrease plaque vulnerability and subsequent plaque rupture through
      activation of autophagy.

PMID- 25768245
TI  - Multiple concomitant cranial nerve palsies secondary to preeclampsia.
AB  - A 32-year-old primigravid woman developed pre-eclampsia after delivery of twins
      along with left fifth, sixth, and seventh cranial neuropathies. She also had
      evidence of hepatic and renal involvement. Results of patient evaluation were
      otherwise unremarkable, and the palsies completely resolved over 3 months after
      treatment with valacyclovir and systemic corticosteroids. 

PMID- 25768244
TI  - Triple antithrombotic therapy versus dual antiplatelet therapy in patients with
      atrial fibrillation undergoing drug-eluting stent implantation.
AB  - BACKGROUND: The optimal antithrombotic regimen in patients with atrial
      fibrillation (AF) undergoing drug-eluting stent (DES) implantation for complex
      coronary artery disease is unclear. We compared the net clinical outcomes of
      triple antithrombotic therapy (TAT; aspirin, thienopyridine, and warfarin) and
      dual antiplatelet therapy (DAPT; aspirin and thienopyridine) in AF patients who
      had undergone DES implantation. METHODS: A total of 367 patients were enrolled
      and analyzed retrospectively; 131 patients (35.7%) received TAT and 236 patients
      (64.3%) received DAPT. DAPT and warfarin were maintained for a minimum of 12 and
      24 months, respectively. The primary endpoint was the 2-year net clinical
      outcomes, a composite of major bleeding and major adverse cardiac and cerebral
      events (MACCE). Propensity score-matching analysis was carried out in 99 patient
      pairs. RESULTS: The 2-year net clinical outcomes of the TAT group were worse than
      those of the DAPT group (34.3 vs. 21.1%, P=0.006), which was mainly due to the
      higher incidence of major bleeding (16.7 vs. 4.6%, P<0.001), without any
      significant increase in MACCE (22.1 vs. 17.7%, P=0.313). In the multivariate
      analysis, TAT was an independent predictor of worse net clinical outcomes (odds
      ratio 1.63, 95% confidence interval 1.06-2.50) and major bleeding (odds ratio
      3.54, 95% confidence interval 1.65-7.58). After propensity score matching, the
      TAT group still had worse net clinical outcomes and a higher incidence of major
      bleeding compared with the DAPT group. CONCLUSION: In AF patients undergoing DES
      implantation, prolonged administration of TAT may be harmful due to the
      substantial increase in the risk for major bleeding without any reduction in
      MACCE.

PMID- 25768246
TI  - Positive Apraclonidine Test in Horner Syndrome Caused by Thalamic Hemorrhage.
AB  - Reversal of anisocoria following instillation of apraclonidine 0.5% has been
      reported in Horner syndrome caused by lesions of the central and peripheral
      nervous system. The shortest documented latency between symptom onset and a
      positive apraclonidine test is 36 hours, occurring in a patient with a
      pontomedullary infarct. We present the case of a 69-year-old man with Horner
      syndrome due to thalamic hemorrhage in whom apraclonidine testing demonstrated
      reversal of anisocoria 4 days after symptom onset. This is the first reported
      case of a positive apraclonidine test in a Horner syndrome caused by a lesion at
      this site. It suggests that apraclonidine testing is useful in confirming the
      diagnosis within days of onset even in a lesion located at the most proximal
      portion of the oculosympathetic pathway. 

PMID- 25768247
TI  - Highlights From the 2014 Joint Americas Committee for Treatment and Research in
      Multiple Sclerosis (ACTRIMS)-European Committee for Treatment and Research in
      Multiple Sclerosis (ECTRIMS).

PMID- 25768248
TI  - HALF-DOSE PHOTODYNAMIC THERAPY COMBINED WITH BEVACIZUMAB FOR POLYPOIDAL CHOROIDAL
      VASCULOPATHY.
AB  - PURPOSE: To evaluate the efficacy of half-dose photodynamic therapy (PDT)
      combined with intravitreal bevacizumab (IVB) for polypoidal choroidal
      vasculopathy. METHODS: For this retrospective comparative study, data from 57
      patients (63 eyes) with at least 12 months of follow-up were reviewed. Full-dose
      or half-dose PDT combined with a single IVB treatment was performed according to
      the time period. From 3 months after the initial combination treatment,
      retreatment was performed mainly using anti-vascular endothelial growth factor
      injections on an as-needed basis. RESULTS: Consecutively, 33 eyes were treated
      with full-dose PDT/IVB and 30 eyes with half-dose PDT/IVB. At Month 3, half-dose
      PDT/IVB induced negligible damage to the physiologic choroid but was inferior to
      full-dose PDT/IVB in achieving complete polyp closure (43.3% vs. 72.7%, P =
      0.018) and improving mean best-corrected visual acuity (20/66 vs. 20/43, P =
      0.020). At Month 12, the half-dose group achieved comparable visual improvement
      (20/51 vs. 20/40, P = 0.254) but required more additional injections (a mean of
      2.80 vs. 1.03, P = 0.004). CONCLUSION: Despite inferior efficacy in inducing
      polyp closure, half-dose PDT/IVB followed by additional injections showed
      promising visual outcomes while avoiding damage to the physiologic choroid.
      Further long-term study is needed to evaluate the efficacy of half-dose PDT plus
      anti-vascular endothelial growth factor for polypoidal choroidal vasculopathy.

PMID- 25768249
TI  - PREVENTION OF RADIATION-INDUCED RETINOPATHY WITH AMIFOSTINE IN WISTAR ALBINO
      RATS.
AB  - PURPOSE: To evaluate the radioprotective efficacy of amifostine on irradiated
      mature rat retina. METHODS: A total of 108 Wistar albino rats were categorized
      into 3 groups, namely, apoptosis (n = 48), acute effects (n = 40), and late
      changes in retinal cell layers (n = 20). Each group was further subcategorized
      into 4 arms: control, amifostine (A), radiotherapy + placebo (RT), and RT + A
      arms, respectively. Intraperitoneal amifostine (260 mg/kg) was administrated to A
      and RT + A arms 30 minutes before irradiation. Control and A groups were sham
      irradiated, whereas a single dose of 20 Gy whole-cranium irradiation was
      delivered to RT and RT + A arms. Apoptosis was assessed in 8, 12, and 18 hours
      after irradiation. Electron microscope was used 2 weeks after irradiation for
      evaluation and scoring of early morphologic changes in retina. Late effects were
      assessed and scored accordingly by using both the electron and the light
      microscope on Week 10. RESULTS: At acute phase, although no notable change was
      seen in 8 hours, significant increase in apoptosis was detected in 12 hours in RT
      arm (P = 0.029). Comparative analyses between the groups in 3 different time
      points displayed a higher apoptotic rate in RT group than the RT + A group (P =
      0.008). Similarly, comparisons between groups for late effects on the basis of
      electron microscopic findings revealed lower scores in the RT + A than the RT arm
      (P < 0.001). CONCLUSION: This study suggested a potential radioprotective role
      for amifostine on mature rat retina by reducing radiation-induced apoptosis in
      retinal cells. These results form a basis for such preclinical investigations and
      call for future clinical studies.

PMID- 25768250
TI  - EPITHELIAL DOWNGROWTH IN THE VITREOUS CAVITY AND ON THE RETINA IN ENUCLEATED
      SPECIMENS AND IN EYES WITH VISUAL POTENTIAL.
AB  - PURPOSE: To report clinical course and visual and anatomical outcomes of six eyes
      with histopathologically confirmed vitreous cavity and retina epithelial
      downgrowth. METHODS: This is a retrospective 15-year review of archived
      pathologic slides and corresponding medical records of patients with vitreous
      cavity and retina epithelial downgrowth. Posterior segment epithelial downgrowth
      was defined as epithelial or goblet cells in the vitreous cavity or on the
      surface of the retina. RESULTS: Histopathologic diagnosis of epithelial
      downgrowth was made in 122 patients. Of those, 6 patients (5%) had vitreous
      cavity and retina epithelial downgrowth. Three patients developed blind painful
      eye, and epithelial downgrowth was identified in enucleated specimens. The other
      three eyes with visual potential presented with tractional retinal detachments.
      Epithelial downgrowth was identified in epiretinal membranes obtained during pars
      plana vitrectomy. The latter group had more previous surgeries (P = 0.03), and
      all had keratoprosthesis implantation as their last surgery. All three had
      pathologic specimens obtained at the time of the keratoprosthesis implantation;
      no anterior segment epithelial downgrowth was noted in two patients, and one
      patient had involvement of corneal button, iris, and posterior capsule. Final
      visual acuity ranged from hand motion to light perception. CONCLUSION: In the
      current study, vitreous cavity and retina epithelial downgrowth occurred after
      multiple intraocular surgeries, including repair of the open globe injuries both
      in enucleated specimens and in eyes with visual potential. In eyes with visual
      potential, keratoprosthesis implantation seems to predispose the development of
      posterior segment epithelial downgrowth.

PMID- 25768251
TI  - EPIRETINAL MEMBRANES IN NEOVASCULAR AGE-RELATED MACULAR DEGENERATION: Effect on
      Outcomes of Anti-vascular Endothelial Growth Factor Therapy.
AB  - PURPOSE: To iatients with neovascular age-related macular degenernvestigate the
      role of epiretinal membrane (ERM) on outcomes of anti-vascular endothelial growth
      factor therapy in pation (nAMD). METHODS: This study is a retrospective
      observational case series and was conducted at the Gazi University School of
      Medicine, Ankara, Turkey. The reports of the patients with a diagnosis of new
      onset nAMD, who were aged at least 50 years and treated with intravitreal anti
      vascular endothelial growth factors (ranibizumab or bevacuzimab) between October
      2010 and September 2013 in our retina clinic, were reviewed for the vitreomacular
      interface changes. RESULTS: The study included 90 eyes of 90 patients with nAMD.
      The mean age of the patients was 70 +/- 7.5 years, with 35 (38.9%) being male and
      55 (61.1%) being female. According to the examinations with optical coherence
      tomography and B-mode ultrasonography, 43 patients had "concurrent" vitreomacular
      adhesion (30 focal, 13 broad; Group 1). Twenty-nine patients had complete
      posterior vitreous detachment (Group 2) and 18 patients (Group 3) had ERM. The
      number of injections was highest for the patients with ERM (Group 3), and this
      difference was statistically significant (P < 0.001). The mean interval between
      injections and the mean longest interval were shorter in Group 3 (P < 0.05).
      CONCLUSION: The presence of ERM in association with nAMD seems to increase the
      number of anti-vascular endothelial growth factor injections and decrease the
      injection intervals for the treatment of nAMD. Although the anatomical and
      functional results are similar in eyes with or without ERM, the increased need
      for anti-vascular endothelial growth factors may mean that these membranes may
      decrease the penetration of the drugs through these membranes, which may act as a
      physical barrier. Additionally, increased inflammation in patients with ERM
      probably requires more frequent injections.

PMID- 25768252
TI  - Reactivation of retinopathy of prematurity after ranibizumab treatment.
AB  - INTRODUCTION: Retinopathy of prematurity (ROP) is a vasoproliferative disorder of
      the developing retina and a significant cause of childhood blindness around the
      world. Vascular endothelial growth factor (VEGF) plays an important role in the
      neovascular phase of ROP, and treatment with an anti-VEGF agent is justified in
      select cases. Bevacizumab is the most commonly used anti-VEGF agent in ROP, but
      ranibizumab has a shorter half-life with the potential for decreased systemic
      toxicity. The purpose of this study is to report our experience with anti-VEGF
      agents for the treatment of ROP. METHODS: A retrospective chart review was
      performed on consecutive infants screened for ROP. Infants treated with
      peripheral retinal ablation, bevacizumab 0.625 mg/0.025 mL, or ranibizumab 0.25
      mg/0.025 mL were specifically identified for review of their clinical outcomes.
      All treated infants had at least 6 months of follow-up with the treating team and
      were examined until total regression of ROP. RESULTS: One hundred and forty-two
      infants were screened over a two-year period. Six infants received anti-VEGF
      agents, with a mean gestational age of 23.48 weeks and mean birth weight of 620
      g. Ten eyes from the six infants received anti-VEGF treatment. All ten eyes
      demonstrated initial regression of ROP. However, ROP reactivation occurred in 5/6
      (83%) eyes treated with ranibizumab, on average 5.9 weeks after treatment;
      whereas none of the 4 eyes treated with bevacizumab experienced reactivation (P <
      0.05). One infant who received a unilateral injection of ranibizumab demonstrated
      bilateral regression of ROP. CONCLUSION: The role of anti-VEGF treatment for ROP
      is still being evaluated. Although the shorter half-life of ranibizumab makes it
      an attractive option, reactivation of ROP is possible. Physicians and families
      should be aware of this to follow infants closely for an extended period of time.

PMID- 25768253
TI  - REFRACTILE DRUSEN: Clinical Imaging and Candidate Histology.
AB  - PURPOSE: To evaluate eyes with refractile drusen using clinical imaging and to
      identify candidate histologic correlates of refractile drusen. METHODS:
      Refractile drusen were defined as drusenoid material containing small refractile
      spherules. Retrospective analysis of color, autofluorescence, and spectral domain
      optical coherence tomography images of eyes with refractile drusen was performed
      to characterize the morphology and topography of these lesions. Macular sections
      from donor eyes were processed with a von Kossa stain for calcium phosphate and
      viewed by light microscopy. Punches of retinal pigment epithelium-choroid from
      donors with geographic atrophy were prepared for transmission electron
      microscopy. RESULTS: Fundus findings of 14 eyes of 10 patients with age-related
      macular degeneration (age, 82.9 +/- 5.6 years) were evaluated. A generalized loss
      of autofluorescence signal over refractile drusen appeared to spread over a
      larger area than each druse, for drusen located centrally. By color fundus
      photography, refractile drusen showed corresponding depigmentation around drusen
      that were located in the center of the macula. Optical coherence tomography
      imaging of refractile drusen showed hyperreflective dots. In the histologic
      specimens, drusen contained many small spherules rich in calcium phosphate.
      Ultrastructural examination of the spherules showed complex assemblies consisting
      of concentric shells containing thin layers of calcium. CONCLUSION: Refractile
      drusen appear to be a stage of drusen regression marked by loss of retinal
      pigment epithelium, thus contributing to the development of geographic atrophy.
      Calcium-containing spherules appear to account for the glistening appearance.

PMID- 25768254
TI  - Multiplane peripheral vitreous dissection with perfluoro-n-octane and
      triamcinolone acetonide.

PMID- 25768255
TI  - MyD-88 L265P mutations are present in some cases of vitreoretinal lymphoma.
AB  - PURPOSE: To determine whether Myd88 L265P mutations occur in diffuse large B-cell
      vitreoretinal lymphomas. METHODS: The formalin-fixed paraffin-embedded cells from
      three patients with classic clinical findings of vitreoretinal lymphoma that also
      had histologic confirmation were evaluated using a validated amplification
      refractory mutation system polymerase chain reaction to determine the presence of
      the mutation. RESULTS: The 74 +/- 2 base pair product seen from the mutated Myd
      88 protein was noted in 2 of the 3 cases. CONCLUSION: Myd-88 L265P constitutive
      activating mutations are present in at least some cases of the diffuse large B
      cell lymphoma form of vitreoretinal lymphoma. Further studies on the incidence of
      this mutation in retinal lymphomas are warranted.

PMID- 25768256
TI  - Cadherin 17 is a sensitive and specific marker for metanephric adenoma.
AB  - Metanephric adenoma (MA) is a rare benign renal neoplasm that shares morphologic
      and immunophenotypic overlap with epithelial-predominant Wilms tumor (e-WT) and
      with the solid variant of papillary renal cell carcinoma (s-PRCC). Cadherin 17
      (CDH17) is expressed primarily in the normal intestine and digestive tract tumors
      and has not been detected in tumors from other sites including the kidney. We
      investigated the diagnostic utility of CDH17 in differentiating between MA, e-WT,
      and s-PRCC. Immunohistochemical analysis for CDH17, CD57, AMACR, WT-1, and CDX2
      was performed on 17 e-WTs, 15 s-PRCCs, and 21 MAs and assessed on the basis of a
      combined score of extent and intensity. Normal adult kidney parenchyma was
      negative for CDH17 staining. CDH17 was expressed in the late stages of fetal
      kidney development at the junction of the glomerular space and proximal nephron.
      The majority of MAs (81%) demonstrated membranous CDH17 immunoreactivity in all
      components (acinar, tubular, and papillary), whereas all cases of e-WTs and s
      PRCCs were negative (P<0.0001). WT-1 was negative in s-PRCC and was positive in
      all cases of e-WT and MA. All MAs were strongly positive for CD57; however, this
      marker was also moderate to strongly positive in 6 (35%) e-WTs and 2 (13%) s
      PRCCs. AMACR was strongly positive in all s-PRCCs, but moderate reactivity was
      seen in 3 (17%) e-WTs and 2 MAs (10%). CDH17 is a sensitive (81%) and highly
      specific (100%) marker for MA and should be considered in the
      immunohistochemistry panel for distinguishing MA from its mimics.

PMID- 25768257
TI  - Cytokeratin-positive fibroblastic reticular cell tumor with follicular dendritic
      cell features: a case report and review of the literature.
AB  - Fibroblastic reticular cell (FRC) neoplasms, which are one of the histiocyte
      tumor types, are very rare. Here we report a cytokeratin (CK)-positive FRC
      neoplasm having features of follicular dendritic cells in a 54-year-old woman
      with right axillary lymph node swelling. The resected lymph node showed multiple
      nodular aggregations simulating and replacing normal follicles. The tumor cells
      had a uniform, large and oval to polygonal shape, abundant cytoplasm, and various
      sizes of nuclei with central eosinophilic nucleoli and coarse nuclear chromatin.
      They were positive for CK AE1/AE3+CAM5.2, CK7, tenascin C, l-caldesomone, and
      CD21, weakly positive for S100, and negative for CD1a. Ultrastructurally, the
      tumor cells had long interdigitating microvillus-like cell processes and oval to
      elongated vesicular nuclei. In addition, the intercellular spaces contained
      accumulations of collagen, and some tumor cells had desmosomal-like junctions.
      These findings suggest that the present case is a CK-positive FRC tumor with
      follicular dendritic cell features. 

PMID- 25768258
TI  - Update on abusive head trauma.
AB  - PURPOSES OF REVIEW: This article provides an update on abusive head trauma (AHT),
      focusing on new developments most salient to the emergency medicine clinician,
      including epidemiology, clinical recognition, diagnostic work-up, management of
      neurologic injury, and public health implications. RECENT FINDINGS: The recent
      literature has focused on honing the clinician's ability to recognize AHT and its
      immediate sequelae, to more accurately distinguish between abusive and accidental
      head injuries by patterns of neuroimaging and retinal hemorrhages, and to
      appreciate the long-term impacts. Specifically, both a clinical prediction rule
      and biomarker show promise, and new research advocates for the early
      identification of subclinical seizures as well as cervical spine injuries.
      SUMMARY: The emergency medicine provider must be able to recognize and manage
      children who may have AHT and to appreciate when the diagnostic findings warrant
      consultation with a child protection team. These authors summarize the recent and
      notable advances in our understanding of AHT.

PMID- 25768259
TI  - New life for an old antibiotic.
AB  - Restoring the antibacterial properties of existing antibiotics is of great
      concern. Herein, we present, for the first time, the formation and deposition of
      stable antibiotic nanoparticles (NPs) on graphene oxide (GO) sheets by a facile
      one-step sonochemical technique. Sonochemically synthesized graphene
      oxide/tetracycline (GO/TET) composite shows enhanced activity against both
      sensitive and resistant Staphylococcus aureus (S. aureus). The size and
      deposition of tetracycline (TET) nanoparticles on GO can be controlled by varying
      the sonication time. The synthesized NPs ranged from 21 to 180 nm. Moreover,
      ultrasonic irradiation does not cause any structural and chemical changes to the
      TET molecule as confirmed by Fourier transform infrared spectroscopy (FTIR). The
      virtue of pi-pi stacking between GO and TET additionally facilitate the coating
      of TET NPs upon GO. A time dependent release kinetics of TET NPs from the GO
      surface is also monitored providing important insights regarding the mechanism of
      antibacterial activity of GO/TET composites. Our results show that the GO/TET
      composite is bactericidal in nature, resulting in similar values of minimal
      inhibitory concentration (MIC) and minimal bactericidal concentration (MBC). This
      composite is found to be active against TET resistant S. aureus at a
      concentration four times lower than the pristine TET. The sensitive S. aureus
      follows the same trend showing six times lower MIC values compared to pristine
      TET. GO shows no activity against both sensitive and resistant S. aureus even at
      a concentration as high as 1 mg/mL but influences the biocidal activity of the
      GO/TET composite. We propose that the unique structure and composition manifested
      by GO/TET composites may be further utilized for different formulations of
      antibiotics with GO. The sonochemical method used in this work can be precisely
      tailored for the stable deposition of a variety of antibiotics on the GO surface
      to reduce health risks and increase the spectrum of applications. 

PMID- 25768260
TI  - Avoiding Anomalous Tendon Harvest at the Pes Anserinus Insertion.

PMID- 25768261
TI  - Modified Protocol Decreases Surgical Site Infections after Total Knee
      Arthroplasty.

PMID- 25768262
TI  - Frost decreases content of sugars, ascorbic acid and some quercetin glycosides
      but stimulates selected carotenes in Rosa canina hips.
AB  - Primary and secondary metabolites of Rosa canina hips were determined by HPLC/MS
      during ripening and after frost damage. Rose hips were harvested six times from
      the beginning of September until the beginning of December. Color parameters a*,
      b* and L* decreased during maturation. Glucose and fructose were the predominant
      sugars representing up to 92% total sugars, and citric acid was the major organic
      acid detected in rose hips (constituting up to 58% total organic acids). Total
      sugar and ascorbic acid content significantly decreased after frost damage; from
      42.2 to 25.9 g 100 g(-1) DW for sugars and from 716.8 to 176.0 mg 100 g(-1) DW
      for ascorbic acid. Conversely, beta-carotene and lycopene levels increased in
      frostbitten rose hips to 22.1 and 113.2 mg 100 g(-1) DW, respectively. In
      addition to cyanidin-3-glucoside (highest level in hips was 125.7 MUg 100 g (-1)
      DW), 45 different phenolic compounds have been identified. The most abundant were
      proanthocyanidins (their levels amounted up to 90% of total flavanol content) and
      their content showed no significant differences during maturation. The levels of
      catechin, phloridzin, flavanones and several quercetin glycosides were highest on
      the first three sampling dates and decreased after frost. Antioxidant capacity
      similarly decreased in frostbitten rose hips. Total phenolic content increased
      until the third sampling and decreased on later samplings.

PMID- 25768263
TI  - Reference-free unwarping of single-shot spatiotemporally encoded MRI using
      asymmetric self-refocused echoes acquisition.
AB  - This paper presents a phase evolution rewinding algorithm for correcting the
      geometric and intensity distortions in single-shot spatiotemporally encoded
      (SPEN) MRI with acquisition of asymmetric self-refocused echo trains. Using the
      field map calculated from the phase distribution of the source image, the off
      resonance induced phase errors are successfully rewound through deconvolution.
      The alias-free partial Fourier transform reconstruction helps improve the signal
      to-noise ratio of the field maps and the output images. The effectiveness of the
      proposed algorithm was validated through 7 T MRI experiments on a lemon, a water
      phantom, and in vivo rat head. SPEN imaging was evaluated using rapid acquisition
      by sequential excitation and refocusing (RASER) which produces uniform T2
      weighting. The results indicate that the new technique can more robustly deal
      with the cases in which the images obtained with conventional single-shot spin
      echo EPI are difficult to be restored due to serious field variations.

PMID- 25768264
TI  - Competing Speech Perception in Middle Age.
AB  - PURPOSE: This research forum article summarizes research from our laboratory that
      assessed middle-aged adults' ability to understand speech in the presence of
      competing talkers. METHOD: The performance of middle-aged adults on laboratory
      based speech understanding tasks was compared to that of younger and older
      adults. RESULTS: Decline in the ability to understand speech in complex listening
      environments can be demonstrated in midlife. The specific auditory and cognitive
      contributors to these problems have yet to be established. CONCLUSION: There is
      evidence that the ability to understand a target speech message in the presence
      of competing speech messages changes relatively early in the aging process. The
      nature and impact of these changes warrant further investigation.

PMID- 25768265
TI  - Texture features on T2-weighted magnetic resonance imaging: new potential
      biomarkers for prostate cancer aggressiveness.
AB  - To explore contrast (C) and homogeneity (H) gray-level co-occurrence matrix
      texture features on T2-weighted (T2w) Magnetic Resonance (MR) images and apparent
      diffusion coefficient (ADC) maps for predicting prostate cancer (PCa)
      aggressiveness, and to compare them with traditional ADC metrics for
      differentiating low- from intermediate/high-grade PCas. The local Ethics
      Committee approved this prospective study of 93 patients (median age, 65 years),
      who underwent 1.5 T multiparametric endorectal MR imaging before prostatectomy.
      Clinically significant (volume >=0.5 ml) peripheral tumours were outlined on
      histological sections, contoured on T2w and ADC images, and their pathological
      Gleason Score (pGS) was recorded. C, H, and traditional ADC metrics (mean,
      median, 10th and 25th percentile) were calculated on the largest lesion slice,
      and correlated with the pGS through the Spearman correlation coefficient. The
      area under the receiver operating characteristic curve (AUC) assessed how
      parameters differentiate pGS = 6 from pGS >= 7. The dataset included 49
      clinically significant PCas with a balanced distribution of pGS. The Spearman rho
      and AUC values on ADC were: -0.489, 0.823 (mean); -0.522, 0.821 (median); -0.569,
      0.854 (10th percentile); -0.556, 0.854 (25th percentile); -0.386, 0.871 (C);
      0.533, 0.923 (H); while on T2w they were: -0.654, 0.945 (C); 0.645, 0.962 (H).
      AUC of H on ADC and T2w, and C on T2w were significantly higher than that of the
      mean ADC (p = 0.05). H and C calculated on T2w images outperform ADC parameters
      in correlating with pGS and differentiating low- from intermediate/high-risk
      PCas, supporting the role of T2w MR imaging in assessing PCa biological
      aggressiveness.

PMID- 25768267
TI  - Toxicity of CeO2 nanoparticles - the effect of nanoparticle properties.
AB  - Conflicting reports on the toxicity of CeO2 nanomaterials have been published in
      recent years, with some studies finding CeO2 nanoparticles to be toxic, while
      others found it to have protective effects against oxidative stress. To
      investigate the possible reasons for this, we have performed a comprehensive
      study on the physical and chemical properties of nanosized CeO2 from three
      different suppliers as well as CeO2 synthesized by us, and tested their toxicity.
      For toxicity tests, we have studied the effects of CeO2 nanoparticles on a Gram
      negative bacterium Escherichia coli in the dark, under ambient and UV
      illuminations. We have also performed toxicity tests on the marine diatom
      Skeletonema costatum under ambient and UV illuminations. We found that the CeO2
      nanoparticle samples exhibited significantly different toxicity, which could
      likely be attributed to the differences in interactions with cells, and possibly
      to differences in nanoparticle compositions. Our results also suggest that
      toxicity tests on bacteria may not be suitable for predicting the ecotoxicity of
      nanomaterials. The relationship between the toxicity and physicochemical
      properties of the nanoparticles is explicitly discussed in the light of the
      current results. 

PMID- 25768266
TI  - Oxytocin and HPA stress axis reactivity in postpartum women.
AB  - BACKGROUND: Lactation is thought to buffer stress reactivity via oxytocin (OT).
      Dysregulation of the HPA axis has been reported in women with postpartum
      depression (PPD). The co-occurrence of PPD and lactation failure suggests that
      abnormalities in OT signaling may play a role in PPD. We hypothesized that
      abnormal OT signaling is implicated in dysregulated HPA axis reactivity among
      postpartum women with mood symptoms. In a prospective perinatal cohort, we tested
      associations between OT levels during breastfeeding and stress reactivity.
      METHODS: We recruited 52 pregnant women who intended to breastfeed, among whom 47
      underwent a standardized stressor, the Trier Social Stress Test (TSST), at 8
      weeks postpartum. 39 were breastfeeding at time of TSST. We assessed mood
      symptoms using validated instruments and defined as symptomatic women with EPDS
      >= 10 and/or Spielberger >= 34. Following IV placement for blood draws, women
      breastfed their infants and then underwent the TSST. Mothers' hormone responses
      were quantified. RESULTS: Among symptomatic breastfeeding women (N=11;
      asymptomatic N=28), we found lower OT levels during breastfeeding (p<0.05) and
      higher CORT levels (p<0.05) both during breastfeeding and the TSST, as compared
      to asymptomatic breastfeeding women. In a mixed effects model examining CORT
      reactivity by symptom group and OT AUC, we observed a paradoxical response in
      symptomatic breastfeeding women during the TSST (group * time * OT AUC p<0.05);
      higher OT AUC was associated with higher CORT. CONCLUSIONS: In all breastfeeding
      women, the surge of OT during feeding appears to buffer subsequent stress-induced
      CORT secretion. However, in symptomatic breastfeeding women, we found a positive
      correlation between OT AUC and CORT, instead of the expected negative
      correlation, which we found among asymptomatic women.

PMID- 25768268
TI  - Obituary: John O. Corliss, February 23, 1922 - December 21, 2014.

PMID- 25768269
TI  - Advances in the treatment of relapsed/refractory acute lymphoblastic leukemia: a
      case study compendium.
AB  - Acute lymphoblastic leukemia (ALL) is a heterogeneous hematologic malignancy
      characterized by proliferation of immature lymphoid cells throughout the bone
      marrow and peripheral blood. Most cases are diagnosed before the age of 20 years.
      Adults have a worse prognosis than children. Approximately half of adult ALL
      patients relapse after their initial treatment. There is no standard treatment
      for ALL; strategies vary according to the patient's age, comorbidities, and
      Philadelphia chromosome status. Regimens used in pediatric patients are being
      adapted for use in adults. Frontline management can include hyperfractionated
      cyclophosphamide, vincristine, doxorubicin, and dexamethasone alternating with
      cycles of high-dose methotrexate and cytarabine (hyper-CVAD) and the Berlin
      Frankfurt-Munster regimen. Relapsed/refractory patients have several options,
      including a regimen consisting of fludarabine, high-dose cytarabine, and
      granulocyte colony-stimulating factor (FLAG); tyrosine kinase inhibitors; and
      chemotherapy. The US Food and Drug Administration recently approved 3 therapies
      for these patients: clofarabine, nelarabine, and vincristine sulfate liposome
      injection, a modified formulation of vincristine that allows the drug to be
      administered at a higher dosage. Several novel strategies are currently under
      investigation, including the monoclonal antibody blinatumomab, a bispecific T
      cell engager that targets the B-cell-specific antigen CD19 and activates T cells
      to exert cytotoxic activity against the target B cell. This clinical roundtable
      monograph features case studies that illustrate important points in the
      management of adult patients with relapsed/refractory ALL.

PMID- 25768273
TI  - At the physical limit - chemosensation in sperm.
AB  - Many cells probe their environment for chemical cues. Some cells respond to
      picomolar concentrations of neuropeptides, hormones, pheromones, or
      chemoattractants. At such low concentrations, cells encounter only a few
      molecules. The mechanistic underpinnings of single-molecule sensitivity are not
      known for any eukaryotic cell. Sea urchin sperm offer a unique model to unveil in
      quantitative terms the principles underlying chemosensation at the physical
      limit. Here, we discuss the mechanisms of such exquisite sensitivity and the
      computational operations performed by sperm during chemotactic steering.
      Moreover, we highlight commonalities and differences between signalling in sperm
      and photoreceptors and among sperm from different species. 

PMID- 25768275
TI  - New developments in acute lymphoblastic leukemia.
AB  - Acute lymphoblastic leukemia (ALL) occurs in both children and adults.
      Significant improvements in survival outcomes have been realized over the last
      decade for all age groups with de novo ALL. Frontline treatment incorporates a
      tailored approach, based on factors such as the patient's age and the disease
      subtype. Children, adolescents, and young adults are likely to receive
      intensifying or deintensifying chemotherapy regimens using standard
      chemotherapeutics (eg, anthracyclines, vincristine, asparaginase) based on risk
      stratification. Older adults appear to benefit from reduced-intensity
      chemotherapy regimens, which incorporate targeted therapy (eg, monoclonal
      antibodies). New data suggest that a more intensive pediatric protocol might be
      feasible in adult patients. More than half of ALL patients relapse, and their
      limited survival has led to the development of novel approaches. Recently
      approved chemotherapeutic agents include clofarabine, nelarabine, asparaginase
      Erwinia chrysanthemi, and vincristine sulfate liposome injection, a novel
      formulation that permits administration of a higher dosage of vincristine than
      that used in standard regimens. Approaches under investigation include cell
      therapy using autologous T-cell technologies, antibody-drug conjugates, and
      agents targeting common gene mutations. Many novel agents are undergoing
      evaluation in both the frontline and relapsed settings.

PMID- 25768277
TI  - Atypical presentation of gastrointestinal stromal tumor masquerading as a large
      duodenal cyst: A case report.
AB  - INTRODUCTION: Gastrointestinal stromal tumors (GIST) are solid tumors. A duodenal
      GIST masquerading as a cystic lesion has never been reported. We report a large
      duodenal cyst that finally turned out to be a GIST and was managed without a
      pancreaticoduodenectomy (PD). PRESENTATION OF CASE: A 55 year old lady presented
      with painful lump in epigastrium. A CT scan revealed a large exophytic cystic
      lesion from the duodenum with a small solid component. An endoscopy showed a
      polypoid lesion in the second part of the duodenum adjacent to what looked like a
      diverticulum. A sleeve duodenal resection, duodeno-duodenostomy and pyloric
      exclusion was done. The histopathology was duodenal GIST. DISCUSSION: This case
      posed diagnostic difficulty as it was thought to be either a duplication cyst or
      a diverticulum of duodenum. The odd point was the small solid component in it. We
      considered the possibility of a malignancy arising in these settings, which is
      has been occasionally reported. To our surprise, it turned out to be a GIST. An
      extensive literature search yielded only four reports that have reported cystic
      GISTS, all arising from the stomach or pancreas where they have been mistaken for
      pseudocysts or even a mucinous cystadenocarcinoma of the pancreas. This is the
      first report of a cystic GIST arising from the duodenum. CONCLUSION: GISTS can
      present as a predominantly cystic lesion and needs to be considered in the
      differential diagnosis of cystic lesions of the duodenum. Local resection is an
      attractive option in select cases and avoids a PD.

PMID- 25768278
TI  - Idiopathic juvenile osteoporosis: A case report and review of the literature.
AB  - INTRODUCTION: Idiopathic Juvenile Osteoporosis is an uncommon condition that has
      few case reports in the literature. Reported series indicate that it is a
      condition classically accompanying vertebral and metaphyseal fractures during the
      immediate pre-puberty years but that seems to develop naturally during puberty.
      Current clinical treatment is complicated because of lack of understanding on the
      origins of Idiopathic Juvenile Osteoporosis. PRESENTATION OF CASE: The 13-year
      old female patient with no former complaints had pain in her left hip while
      walking 2 years ago. Excluding the secondary osteoporosis reasons, the patient
      was diagnosed with Idiopathic Juvenile Osteoporosis and after the medical
      treatment she was followed-up. DISCUSSION: The patient was subjected to a
      rehabilitation program for muscle weakness. She had difficulty in walking as a
      result of prolonged immobilization. At the end of a two-year treatment,
      significant improvement was achieved in muscle strength in the extremities,
      walking distance, and posture. CONCLUSION: With this report, we would like to
      raise awareness about a possible association of persistent fractures with this
      rare metabolic disorder, Idiopathic Juvenile Osteoporosis, which should be
      included in differential diagnosis of patients with persistent appendicular
      skeleton fractures.

PMID- 25768279
TI  - Laparoscopic excision of primary retroperitoneal mucinous cystadenoma and
      malignant predicting factors derived from literature review.
AB  - INTRODUCTION: Primary retroperitoneal mucinous cystic neoplasm is very rare and
      its histogenesis is unclear. PRESENTATION OF CASE: This paper presents the case
      of a 31-year-old female in whom an incidentally detected retroperitoneal cystic
      mass, 6.5cm in size, was successfully resected through laparoscopic approach.
      Pathologic examination revealed a mucinous cystadenoma. The postoperative course
      was uneventful, and the patient remained free of recurrence six months after
      surgery. DISCUSSION: Literature review showed that male sex (p=0.019), and solid
      nodules in cysts (p<0.001) were both significantly associated with malignancy.
      CONCLUSION: When confronted with a cystic mass in the retroperitoneum, a primary
      mucinous cystic neoplasm should be considered and complete surgical removal of
      the tumor without spillage is recommended.

PMID- 25768280
TI  - The role of multifilament structures and lateral interactions in dynamics of
      cytoskeleton proteins and assemblies.
AB  - Microtubules and actin filaments are biopolymer molecules that are major
      components of cytoskeleton networks in biological cells. They play important
      roles in supporting fundamental cellular processes such as cell division,
      signaling, locomotion, and intracellular transport. In cells, cytoskeleton
      proteins function under nonequilibrium conditions that are powered by hydrolysis
      of adenosine triphosphate (ATP) or guanosine triphosphate (GTP) molecules
      attached to them. Although these biopolymers are critically important for all
      cellular processes, the mechanisms that govern their complex dynamics and force
      generation remain not well explained. One of the most difficult fundamental
      issues is to understand how different components of cytoskeleton proteins
      interact together. We develop an approximate theoretical approach for analyzing
      complex processes in cytoskeleton proteins that takes into account the
      multifilament structure, lateral interactions between parallel protofilaments,
      and the most relevant biochemical transitions during the biopolymer growth. It
      allows us to fully evaluate collective dynamic properties of cytoskeleton
      filaments as well as the effect of external forces on them. It is found that for
      the case of strong lateral interactions the stall force of the multifilament
      protein is a linear function of the number of protofilaments. However, for weak
      lateral interactions, deviations from the linearity are observed. We also show
      that stall forces, mean velocities, and dispersions are increasing functions of
      the lateral interactions. Physical-chemical explanations of these phenomena are
      presented. Our theoretical predictions are supported by extensive Monte Carlo
      computer simulations. 

PMID- 25768281
TI  - A DPP-4 inhibitor suppresses fibrosis and inflammation on experimental autoimmune
      myocarditis in mice.
AB  - Myocarditis is a critical inflammatory disorder which causes life-threatening
      conditions. No specific or effective treatment has been established. DPP-4
      inhibitors have salutary effects not only on type 2 diabetes but also on certain
      cardiovascular diseases. However, the role of a DPP-4 inhibitor on myocarditis
      has not been investigated. To clarify the effects of a DPP-4 inhibitor on
      myocarditis, we used an experimental autoimmune myocarditis (EAM) model in Balb/c
      mice. EAM mice were assigned to the following groups: EAM mice group treated with
      a DPP-4 inhibitor (linagliptin) (n = 19) and those untreated (n = 22).
      Pathological analysis revealed that the myocardial fibrosis area ratio in the
      treated group was significantly lower than in the untreated group. RT-PCR
      analysis demonstrated that the levels of mRNA expression of IL-2, TNF-alpha, IL
      1beta and IL-6 were significantly lower in the treated group than in the
      untreated group. Lymphocyte proliferation assay showed that treatment with the
      DPP-4 inhibitor had no effect on antigen-induced spleen cell proliferation.
      Administration of the DPP-4 inhibitor remarkably suppressed cardiac fibrosis and
      reduced inflammatory cytokine gene expression in EAM mice. Thus, the agents
      present in DPP-4 inhibitors may be useful to treat and/or prevent clinical
      myocarditis. 

PMID- 25768282
TI  - Anion-specific effects on the behavior of pH-sensitive polybasic brushes.
AB  - The anion-specific solvation and conformational behavior of weakly basic poly(2
      dimethylamino)ethyl methacrylate (poly(DMA)), poly(2-diethylamino)ethyl
      methacrylate (poly(DEA)), and poly(2-diisopropylamino)ethyl methacrylate
      (poly(DPA)) brushes, with correspondingly increasing inherent hydrophobicity,
      have been investigated using in situ ellipsometric and quartz crystal
      microbalance with dissipation (QCM-D) measurements. In the osmotic brush regime,
      as the initial low concentration of salt is increased, the brushes osmotically
      swell by the uptake of solvent as they become charged and the attractive
      hydrophobic inter- and intrachain interactions are overcome. With increased ionic
      strength, the brushes move into the salted brush regime where they desolvate and
      collapse as their electrostatic charge is screened. Here, as the brushes
      collapse, they transition to more uniform and rigid conformations, which
      dissipate less energy, than similarly solvated brushes at lower ionic strength.
      Significantly, in these distinct regimes brush behavior is not only ionic
      strength dependent but is also influenced by the nature of the added salt based
      on its position in the well-known Hofmeister or lyotropic series, with potassium
      acetate, nitrate, and thiocyanate investigated. The strongly kosmotropic acetate
      anions display low affinity for the hydrophobic polymers, and largely unscreened
      electrosteric repulsions allow the brushes to remain highly solvated at higher
      acetate concentrations. The mildly chaotropic nitrate and strongly chaotropic
      thiocyanate anions exhibit a polymer hydrophobicity-dependent affinity for the
      brushes. Increasing thiocyanate concentration causes the brushes to collapse at
      lower ionic strength than for the other two anions. This study of weak polybasic
      brushes demonstrates the importance of all ion, solvent, and polymer
      interactions. 

PMID- 25768283
TI  - Expression of dicer and its related miRNAs in the progression of prostate cancer.
AB  - Dicer is aberrantly expressed in several types of malignancies. Cleaved by Dicer,
      the small noncoding microRNAs (miRNAs) are considered potential tools for the
      diagnosis and prognosis of cancer. This study investigated the expression of
      miRNAs thought to target Dicer. Expression of 1,205 human miRNAs and miRNA*s were
      examined in four patients with prostate cancer (PCa) by miRNA array in which the
      threshold was set as two-fold. Seventy-three miRNAs and miRNA*s were
      significantly down-regulated while 10 were up-regulated in PCa tissues compared
      with matched histologically normal glands. Of these, miR-29b-1, miR-200a, miR
      370, and miR-31, which were the most down/up-regulated and closely potentially
      target to the Dicer 3' UTR, were investigated further. Tissues of primary tumors
      and matched normal prostate glands from 185 patients with PCa were collected for
      further investigation. Dicer mRNA levels were negatively correlated with miR-29b
      1 (rhos = -0.177, p = 0.017), miR-200a (rhos = -0.489, p < 0.0001) and miR-31
      (rhos = -0.314, p < 0.0001) expression. Compared with adjacent normal glands, PCa
      tissues showed significantly lower miR-200a and miR-31 expression levels.
      Furthermore, in metastatic PCa, the expression levels of miR-200a, miR-370, and
      miR-31 were dramatically higher than in localized PCa. Additionally, elevated
      expression levels of miR-200a and miR-31 appeared to be associated with
      castration-resistant PCa. These findings suggest possibilities that miR-200a and
      miR-31 target Dicer and are involved in the carcinogenesis, migration, and
      behavior of castration-resistant PCa, indicating that they could be potential
      biomarkers for monitoring PCa progression. 

PMID- 25768284
TI  - Targeting Ergosterol biosynthesis in Leishmania donovani: essentiality of sterol
      14 alpha-demethylase.
AB  - Leishmania protozoan parasites (Trypanosomatidae family) are the causative agents
      of cutaneous, mucocutaneous and visceral leishmaniasis worldwide. While these
      diseases are associated with significant morbidity and mortality, there are few
      adequate treatments available. Sterol 14alpha-demethylase (CYP51) in the parasite
      sterol biosynthesis pathway has been the focus of considerable interest as a
      novel drug target in Leishmania. However, its essentiality in Leishmania donovani
      has yet to be determined. Here, we use a dual biological and pharmacological
      approach to demonstrate that CYP51 is indispensable in L. donovani. We show via a
      facilitated knockout approach that chromosomal CYP51 genes can only be knocked
      out in the presence of episomal complementation and that this episome cannot be
      lost from the parasite even under negative selection. In addition, we treated
      wild-type L. donovani and CYP51-deficient strains with 4-aminopyridyl-based
      inhibitors designed specifically for Trypanosoma cruzi CYP51. While potency was
      lower than in T. cruzi, these inhibitors had increased efficacy in parasites
      lacking a CYP51 allele compared to complemented parasites, indicating inhibition
      of parasite growth via a CYP51-specific mechanism and confirming essentiality of
      CYP51 in L. donovani. Overall, these results provide support for further
      development of CYP51 inhibitors for the treatment of visceral leishmaniasis. 

PMID- 25768285
TI  - Circulating autoantibodies against the apolipoprotein B-100 peptides p45 and p210
      in relation to the occurrence of carotid plaques in 64-year-old women.
AB  - OBJECTIVES: Immune responses against oxidized low density lipoprotein (LDL) play
      a key role in atherosclerosis. Previous studies have indicated inverse
      associations between autoantibodies to epitopes in oxidized LDL and
      cardiovascular disease. In this study we investigated the associations between
      autoantibodies against the apolipoprotein B-100 (apoB-100) peptides p45 and p210
      and occurrence of carotid plaques. DESIGN: The study cohort consisted of a
      population-based sample of 64-year-old women with varying degrees of glucose
      tolerance (n=594). To identify and record the occurrence of carotid
      atherosclerotic plaques ultrasonography was used. Measurements of plasma IgM and
      IgG autoantibodies against the native and malondialdehyde (MDA)-modified apoB-100
      peptides p45 and p210 were performed by ELISA. RESULTS: Women with carotid
      plaques were found to have lower levels of IgM MDA-p210 autoantibodies compared
      to plaque-free women. The number of carotid plaques in each subject and the total
      carotid plaque area correlated inversely with IgM MDA-p210 levels (r=-0.11,
      P=0.009 and r=-0.11, P=0.013, respectively). Furthermore, levels of IgM MDA-p210
      above the lowest tertile were associated with an odds ratio of 0.55 (95% CI 0.38
      0.79, P=0.001) for occurrence of carotid plaques, independently of other risk
      markers and statin treatment. Associations between apo-B100 peptide
      autoantibodies and cardiovascular risk factors were generally weak but subjects
      with impaired glucose tolerance had higher levels of IgM against MDA-p210.
      CONCLUSION: The present study demonstrates that high levels of IgM against MDA
      p210 are associated with less severe carotid disease in women. These findings
      provide additional support for a role of immune responses against oxidized LDL in
      cardiovascular disease.

PMID- 25768286
TI  - SPARCoC: a new framework for molecular pattern discovery and cancer gene
      identification.
AB  - It is challenging to cluster cancer patients of a certain histopathological type
      into molecular subtypes of clinical importance and identify gene signatures
      directly relevant to the subtypes. Current clustering approaches have inherent
      limitations, which prevent them from gauging the subtle heterogeneity of the
      molecular subtypes. In this paper we present a new framework: SPARCoC (Sparse
      CoClust), which is based on a novel Common-background and Sparse-foreground
      Decomposition (CSD) model and the Maximum Block Improvement (MBI) co-clustering
      technique. SPARCoC has clear advantages compared with widely-used alternative
      approaches: hierarchical clustering (Hclust) and nonnegative matrix factorization
      (NMF). We apply SPARCoC to the study of lung adenocarcinoma (ADCA), an extremely
      heterogeneous histological type, and a significant challenge for molecular
      subtyping. For testing and verification, we use high quality gene expression
      profiling data of lung ADCA patients, and identify prognostic gene signatures
      which could cluster patients into subgroups that are significantly different in
      their overall survival (with p-values < 0.05). Our results are only based on gene
      expression profiling data analysis, without incorporating any other feature
      selection or clinical information; we are able to replicate our findings with
      completely independent datasets. SPARCoC is broadly applicable to large-scale
      genomic data to empower pattern discovery and cancer gene identification. 

PMID- 25768287
TI  - Impact of porcine epidemic diarrhea on performance of growing pigs.
AB  - The impact of porcine epidemic diarrhea virus (PEDv) infection on the US pork
      industry has mainly been attributed to the mortality that it causes in suckling
      piglets, and, consequently, much effort has been invested in the quantification
      of its effect in sow farms. However, no information on the performance of
      surviving pigs that were exposed to the PEDv as piglets is available. Here, a
      retrospective cohort study to evaluate the impact of porcine epidemic diarrhea
      virus (PEDv) infection on growing pigs' performance, as indicated by mortality,
      average daily gain (ADG), average daily feed intake (ADFI), and feed conversion
      ratio (FCR) was performed using production records from weaned pigs in nursery
      and wean-to-finish sites from sow farms that became PEDv-infected between May
      2013 and June 2014. Production records from the first batch of growing pigs
      weaned in infected flows after the PEDv outbreak ("infected batches") were
      compared with those from pigs weaned within the previous 14 to 120 days ("control
      batches"). Performance records from infected and control batches, paired by flow,
      were compared using non-parametric paired tests. Mortality, ADG and FCR were
      significantly different in PEDv-positive (infected) compared with PEDv-negative
      (control) batches, with a mean increase of mortality and FCR of 11% and 0.5,
      respectively, and a decrease of ADG of 0.16 lb/day. Our results demonstrate a
      poorer performance of growing pigs weaned after a PEDv outbreak compared with
      those weaned within the previous 14-120 days, suggesting that in addition to the
      mortality induced by PEDv in suckling pigs, the disease also impairs the
      performance of surviving pig. These findings help to quantify the impact of PEDv
      infection in the US and, ultimately, contribute to efforts to quantify the cost
      effectiveness of disease prevention and control measures. 

PMID- 25768288
TI  - Correction: A metatranscriptomic approach to the identification of microbiota
      associated with the ant Formica exsecta.

PMID- 25768290
TI  - Impact of phosphatidylethanolamine on the antioxidant activity of alpha
      tocopherol and trolox in bulk oil.
AB  - The amphiphilic phospholipids dioleoylphosphatidylcholine (DOPC) and
      dioleoylphosphatidylethanolamine (DOPE), can form reverse micelles in bulk oils,
      which affects lipid oxidation chemistry. Previous studies showed that reverse
      micelles formed by DOPC and DOPE shorten the oxidation lag phase of stripped
      soybean oil. This study examined how these reverse micelles influence the
      activity of primary antioxidants such as the nonpolar alpha-tocopherol and the
      polar trolox in stripped and commercial soybean oils. The results showed that
      DOPC reverse micelles decreased the activity of 100 MUM alpha-tocopherol or
      trolox. On the other hand, DOPE increased the antioxidant activity of both alpha
      tocopherol and trolox. The polar trolox exhibited better antioxidant activity
      than the nonpolar alpha-tocopherol in the presence of both DOPC and DOPE reverse
      micelles because trolox partitioned more at the interfaces, which was confirmed
      by a fluorescence steady state study. Different ratios of DOPE to DOPC were added
      to oil containing 100 MUM alpha-tocopherol, and antioxidant activity increased
      with increasing DOPE/DOPC ratio. Addition of DOPE to commercial oil inhibited
      lipid oxidation, whetrsd DOPC was ineffective. HPLC showed that DOPE regenerated
      alpha-tocopherol. This study indicates that the antioxidant activity of
      tocopherols could be improved by utilizing phosphatidylethanolamine (PE) to
      engineer the properties of reverse micelles in bulk oil. 

PMID- 25768289
TI  - Behavior training reverses asymmetry in hippocampal transcriptome of the cav3.2
      knockout mice.
AB  - Homozygous Cav3.2 knockout mice, which are defective in the pore-forming subunit
      of a low voltage activated T-type calcium channel, have been documented to show
      impaired maintenance of late-phase long-term potentiation (L-LTP) and defective
      retrieval of context-associated fear memory. To investigate the role of Cav3.2 in
      global gene expression, we performed a microarray transcriptome study on the
      hippocampi of the Cav3.2-/- mice and their wild-type littermates, either naive
      (untrained) or trace fear conditioned. We found a significant left-right
      asymmetric effect on the hippocampal transcriptome caused by the Cav3.2 knockout.
      Between the naive Cav3.2-/- and the naive wild-type mice, 3522 differentially
      expressed genes (DEGs) were found in the left hippocampus, but only 4 DEGs were
      found in the right hippocampus. Remarkably, the effect of Cav3.2 knockout was
      partially reversed by trace fear conditioning. The number of DEGs in the left
      hippocampus was reduced to 6 in the Cav3.2 knockout mice after trace fear
      conditioning, compared with the wild-type naive mice. To our knowledge, these
      results demonstrate for the first time the asymmetric effects of the Cav3.2 and
      its partial reversal by behavior training on the hippocampal transcriptome. 

PMID- 25768291
TI  - Olfactory thresholds of the U.S. Population of home-dwelling older adults:
      development and validation of a short, reliable measure.
AB  - Current methods of olfactory sensitivity testing are logistically challenging and
      therefore infeasible for use in in-home surveys and other field settings. We
      developed a fast, easy and reliable method of assessing olfactory thresholds, and
      used it in the first study of olfactory sensitivity in a nationally
      representative sample of U.S. home-dwelling older adults. We validated our method
      via computer simulation together with a model estimated from 590 normosmics.
      Simulated subjects were assigned n-butanol thresholds drawn from the estimated
      normosmic distribution and based on these and the model, we simulated
      administration of both the staircase and constant stimuli methods. Our results
      replicate both the correlation between the two methods and their reliability as
      previously reported by studies using human subjects. Further simulations
      evaluated the reliability of different constant stimuli protocols, varying both
      the range of dilutions and number of stimuli (6-16). Six appropriately chosen
      dilutions were sufficient for good reliability (0.67) in normosmic subjects.
      Finally, we applied our method to design a 5-minute, in-home assessment of older
      adults (National Social Life, Health and Aging Project, or NSHAP), which had
      comparable reliability (0.56), despite many subjects having estimated thresholds
      above the strongest dilution. Thus, testing with a fast, 6-item constant stimuli
      protocol is informative, and permits olfactory testing in previously inaccessible
      research settings. 

PMID- 25768292
TI  - A constitutive expression system for cellulase secretion in Escherichia coli and
      its use in bioethanol production.
AB  - The production of biofuels from lignocellulosic biomass appears to be attractive
      and viable due to the abundance and availability of this biomass. The hydrolysis
      of this biomass, however, is challenging because of the complex lignocellulosic
      structure. The ability to produce hydrolytic cellulase enzymes in a cost
      effective manner will certainly accelerate the process of making lignocellulosic
      ethanol production a commercial reality. These cellulases may need to be produced
      aerobically to generate large amounts of protein in a short time or anaerobically
      to produce biofuels from cellulose via consolidated bioprocessing. Therefore, it
      is important to identify a promoter that can constitutively drive the expression
      of cellulases under both aerobic and anaerobic conditions without the need for an
      inducer. Using lacZ as reporter gene, we analyzed the strength of the promoters
      of four genes, namely lacZ, gapA, ldhA and pflB, and found that the gapA promoter
      yielded the maximum expression of the beta-galactosidase enzyme under both
      aerobic and anaerobic conditions. We further cloned the genes for two
      cellulolytic enzymes, beta-1,4-endoglucanase and beta-1,4-glucosidase, under the
      control of the gapA promoter, and we expressed these genes in Escherichia coli,
      which secreted the products into the extracellular medium. An ethanologenic E.
      colistrain transformed with the secretory beta-glucosidase gene construct
      fermented cellobiose in both defined and complex medium. This recombinant strain
      also fermented wheat straw hydrolysate containing glucose, xylose and cellobiose
      into ethanol with an 85% efficiency of biotransformation. An ethanologenic strain
      that constitutively secretes a cellulolytic enzyme is a promising platform for
      producing lignocellulosic ethanol. 

PMID- 25768293
TI  - Involvement of the Cdc42 pathway in CFTR post-translational turnover and in its
      plasma membrane stability in airway epithelial cells.
AB  - Cystic fibrosis transmembrane conductance regulator (CFTR) is a chloride channel
      that is expressed on the apical plasma membrane (PM) of epithelial cells. The
      most common deleterious allele encodes a trafficking-defective mutant protein
      undergoing endoplasmic reticulum-associated degradation (ERAD) and presenting
      lower PM stability. In this study, we investigated the involvement of the Cdc42
      pathway in CFTR turnover and trafficking in a human bronchiolar epithelial cell
      line (CFBE41o-) expressing wild-type CFTR. Cdc42 is a small GTPase of the Rho
      family that fulfils numerous cell functions, one of which is endocytosis and
      recycling process via actin cytoskeleton remodelling. When we treated cells with
      chemical inhibitors such as ML141 against Cdc42 and wiskostatin against the
      downstream effector N-WASP, we observed that CFTR channel activity was inhibited,
      in correlation with a decrease in CFTR amount at the cell surface and an increase
      in dynamin-dependent CFTR endocytosis. Anchoring of CFTR to the cortical
      cytoskeleton was then presumably impaired by actin disorganization. When we
      performed siRNA-mediated depletion of Cdc42, actin polymerization was not
      impacted, but we observed actin-independent consequences upon CFTR. Total and PM
      CFTR amounts were increased, resulting in greater activation of CFTR. Pulse-chase
      experiments showed that while CFTR degradation was slowed, CFTR maturation
      through the Golgi apparatus remained unaffected. In addition, we observed
      increased stability of CFTR in PM and reduction of its endocytosis. This study
      highlights the involvement of the Cdc42 pathway at several levels of CFTR
      biogenesis and trafficking: (i) Cdc42 is implicated in the first steps of CFTR
      biosynthesis and processing; (ii) it contributes to the stability of CFTR in PM
      via its anchoring to cortical actin; (iii) it promotes CFTR endocytosis and
      presumably its sorting toward lysosomal degradation. 

PMID- 25768294
TI  - A matched cohort study of standard chemo-radiotherapy versus radiotherapy alone
      in elderly nasopharyngeal carcinoma patients.
AB  - The impact of standard chemo-radiotherapy (CRT) as preferred therapy for elderly
      patients (age>=60 years) with nasopharyngeal carcinoma (NPC) remains unclear.
      Therefore, a strict matched cohort study was conducted to compare the survival
      and treatment toxicity of standard chemo-radiotherapy in the elderly NPC patients
      with those of radiotherapy (RT) alone. From 1998 to 2003, total 498 newly
      diagnosed elderly non-metastatic NPC patients were abstracted and classified into
      two groups by the treatments they received. For each patient in the CRT group, a
      matched pair in RT group was identified by matching for gender, age, histological
      type, T and N classifications, RT dose to primary tumor and neck nodes, and days
      of radiotherapy. Treatment tolerability and toxicity were clarified, and
      treatment outcomes were calculated and compared between the two groups. Two
      groups were well balanced in clinical characteristics because of the strict
      matching conditions. Totally 87 pairs can be assessed according to the criteria.
      The 5-year OS, CSS, FFS, and LR-FFS for CRT and RT groups were 62% versus 40%
      (P=0.013), 67% versus 47% (P=0.018), 65% versus 53% (log-rank: P=0.064, Breslow:
      P=0.048), and 88% versus 72%, (P=0.019), respectively. There was no significant
      difference in 5-year D-FFS between the two groups (75% vs. 73%, P=0.456). The CRT
      group experienced significantly more Grade >=3 acute mucositis (46.0% vs. 28.7%,
      P= 0.019). We concluded that standard chemo-radiotherapy can achieve a reasonable
      local and regional control in elderly NPC patients with acceptable and reversible
      acute toxicity. However, distant metastasis remains the dominant failure pattern.
      When the elderly NPC patients are in good performance status following a complete
      evaluation of overall functional status and comorbidity conditions, standard
      chemo-radiotherapy is worthy of recommendation. 

PMID- 25768295
TI  - Air stable organic salt as an n-type dopant for efficient and stable organic
      light-emitting diodes.
AB  - Air-stable and low-temperature-evaporable n-type dopants are highly desired for
      efficient and stable organic light-emitting diodes (OLEDs). In this work, 2-(2
      Methoxyphenyl)-1,3-dimethyl-1H-benzoimidazol-3-ium iodide (o-MeO-DMBI-I), a
      thermally decomposable precursor of organic radical o-MeO-DMBI, has been employed
      as a novel n-type dopant in OLEDs, because of its air stability, low
      decomposition temperature, and lack of atom diffusion. The n-type electrical
      doping is evidenced by the rapid increase in current density of electron-only
      devices and the large improvement in conductivity, originated from increased
      electron concentration in electron-transport layer (ETL) and reduced electron
      injection barrier. A highly efficient and stable OLED is created using o-MeO-DMBI
      as an n-type dopant in Bphen. Compared with the control device with its high
      temperature-evaporable n-type dopant cesium carbonate (Cs2CO3), o-MeO-DMBI-doped
      device showed an incredible boom in current efficiency from 28.6 to 42.2 cd/A.
      Moreover, the lifetime (T(70%)) of o-MeO-DMBI-doped device is 45 h, more than 20
      times longer than that of the Cs2CO3-doped device (2 h). The enhanced efficiency
      and stability are attributed to the improved balance of holes and electrons in
      the emissive layer, and the eliminated atom diffusion of cesium.

PMID- 25768296
TI  - Correction: Architecture and gene repertoire of the flexible genome of the
      extreme acidophile Acidithiobacillus caldus.

PMID- 25768298
TI  - Activation and deactivation of a robust immobilized Cp*Ir-transfer hydrogenation
      catalyst: a multielement in situ X-ray absorption spectroscopy study.
AB  - A highly robust immobilized [Cp*IrCl2]2 precatalyst on Wang resin for transfer
      hydrogenation, which can be recycled up to 30 times, was studied using a novel
      combination of X-ray absorption spectroscopy (XAS) at Ir L3-edge, Cl K-edge, and
      K K-edge. These culminate in in situ XAS experiments that link structural changes
      of the Ir complex with its catalytic activity and its deactivation. Mercury
      poisoning and "hot filtration" experiments ruled out leached Ir as the active
      catalyst. Spectroscopic evidence indicates the exchange of one chloride ligand
      with an alkoxide to generate the active precatalyst. The exchange of the second
      chloride ligand, however, leads to a potassium alkoxide-iridate species as the
      deactivated form of this immobilized catalyst. These findings could be widely
      applicable to the many homogeneous transfer hydrogenation catalysts with Cp*IrCl
      substructure. 

PMID- 25768297
TI  - Time since onset of disease and individual clinical markers associate with
      transcriptional changes in uncomplicated dengue.
AB  - BACKGROUND: Dengue virus (DENV) infection causes viral haemorrhagic fever that is
      characterized by extensive activation of the immune system. The aim of this study
      is to investigate the kinetics of the transcriptome signature changes during the
      course of disease and the association of genes in these signatures with clinical
      parameters. METHODOLOGY/PRINCIPLE FINDINGS: Sequential whole blood samples from
      DENV infected patients in Jakarta were profiled using affymetrix microarrays,
      which were analysed using principal component analysis, limma, gene set analysis,
      and weighted gene co-expression network analysis. We show that time since onset
      of disease, but not diagnosis, has a large impact on the blood transcriptome of
      patients with non-severe dengue. Clinical diagnosis (according to the WHO
      classification) does not associate with differential gene expression. Network
      analysis however, indicated that the clinical markers platelet count, fibrinogen,
      albumin, IV fluid distributed per day and liver enzymes SGOT and SGPT strongly
      correlate with gene modules that are enriched for genes involved in the immune
      response. Overall, we see a shift in the transcriptome from immunity and
      inflammation to repair and recovery during the course of a DENV infection.
      CONCLUSIONS/SIGNIFICANCE: Time since onset of disease associates with the shift
      in transcriptome signatures from immunity and inflammation to cell cycle and
      repair mechanisms in patients with non-severe dengue. The strong association of
      time with blood transcriptome changes hampers both the discovery as well as the
      potential application of biomarkers in dengue. However, we identified gene
      expression modules that associate with key clinical parameters of dengue that
      reflect the systemic activity of disease during the course of infection. The
      expression level of these gene modules may support earlier detection of disease
      progression as well as clinical management of dengue.

PMID- 25768299
TI  - Regulation of autoimmune germinal center reactions in lupus-prone BXD2 mice by
      follicular helper T cells.
AB  - BXD2 mice spontaneously develop autoantibodies and subsequent glomerulonephritis,
      offering a useful animal model to study autoimmune lupus. Although initial
      studies showed a critical contribution of IL-17 and Th17 cells in mediating
      autoimmune B cell responses in BXD2 mice, the role of follicular helper T (Tfh)
      cells remains incompletely understood. We found that both the frequency of Th17
      cells and the levels of IL-17 in circulation in BXD2 mice were comparable to
      those of wild-type. By contrast, the frequency of PD-1+ CXCR5+ Tfh cells was
      significantly increased in BXD2 mice compared with wild-type mice, while the
      frequency of PD-1+ CXCR5+ Foxp3+ follicular regulatory T (Tfr) cells was reduced
      in the former group. The frequency of Tfh cells rather than that of Th17 cells
      was positively correlated with the frequency of germinal center B cells as well
      as the levels of autoantibodies to dsDNA. More importantly, CXCR5+ CD4+ T cells
      isolated from BXD2 mice induced the production of IgG from naive B cells in an IL
      21-dependent manner, while CCR6+ CD4+ T cells failed to do so. These results
      together demonstrate that Tfh cells rather than Th17 cells contribute to the
      autoimmune germinal center reactions in BXD2 mice.

PMID- 25768300
TI  - Ecological, evolutionary and social constraints on reproductive effort: are hoary
      marmots really biennial breeders?
AB  - Biennial breeding is a rare life-history trait observed in animal species living
      in harsh, unproductive environments. This reproductive pattern is thought to
      occur in 10 of 14 species in the genus Marmota, making marmots useful model
      organisms for studying its ecological and evolutionary implications. Biennial
      breeding in marmots has been described as an obligate pattern which evolved as a
      mechanism to mitigate the energetic costs of reproduction (Evolved Constraint
      hypothesis). However, recent anecdotal evidence suggests that it is a facultative
      pattern controlled by annual variation in climate and food availability
      (Environmental Constraint hypothesis). Finally, in social animals like marmots,
      biennial breeding could result from reproductive competition between females
      within social groups (Social Constraint hypothesis). We evaluated these three
      hypotheses using mark-recapture data from an 8-year study of hoary marmot
      (Marmota caligata) population dynamics in the Yukon. Annual variation in breeding
      probability was modeled using multi-state mark-recapture models, while other
      reproductive life-history traits were modeled with generalized linear mixed
      models. Hoary marmots were neither obligate nor facultative biennial breeders,
      and breeding probability was insensitive to evolved, environmental, or social
      factors. However, newly mature females were significantly less likely to breed
      than older individuals. Annual breeding did not result in increased mortality.
      Female survival and, to a lesser extent, average fecundity were correlated with
      winter climate, as indexed by the Pacific Decadal Oscillation. Hoary marmots are
      less conservative breeders than previously believed, and the evidence for
      biennial breeding throughout Marmota, and in other arctic/alpine/antarctic
      animals, should be re-examined. Prediction of future population dynamics requires
      an accurate understanding of life history strategies, and of how life history
      traits allow animals to cope with changes in weather and other demographic
      influences. 

PMID- 25768302
TI  - 2-(methoxycarbonyl)ethyl as a removable N-protecting group: synthesis of
      indoloisoquinolinones by Pd(II)-catalyzed intramolecular diamination of alkynes.
AB  - Pd(II)-catalyzed double cyclization of 1,2-diarylethynes bearing an N-methyl-N-[2
      (methoxycarbonyl)ethyl]amino and an aminocarbonyl group at the ortho positions of
      the two aromatic rings afforded the tetracyclic N-[2
      (methoxycarbonyl)ethyl]indoloisoquinolinones in good to excellent yields. The N
      [2-(methoxycarbonyl)ethyl] group is readily removed under basic conditions (DBU,
      DMF, 120  degrees C) to afford the corresponding tetracycles with a free indolyl
      nitrogen in excellent yields. The 2-(methoxycarbonyl)ethyl as a removable N
      protecting group is illustrated in other Pd(II)- and Pd(0)-catalyzed and selenium
      mediated transformations. 

PMID- 25768301
TI  - NatB domain-containing CRA-1 antagonizes hydrolase ACER-1 linking acetyl-CoA
      metabolism to the initiation of recombination during C. elegans meiosis.
AB  - The formation of DNA double-strand breaks (DSBs) must take place during meiosis
      to ensure the formation of crossovers, which are required for accurate chromosome
      segregation, therefore avoiding aneuploidy. However, DSB formation must be
      tightly regulated to maintain genomic integrity. How this regulation operates in
      the context of different chromatin architectures and accessibility, and how it is
      linked to metabolic pathways, is not understood. We show here that global histone
      acetylation levels undergo changes throughout meiotic progression. Moreover,
      perturbations to global histone acetylation levels are accompanied by changes in
      the frequency of DSB formation in C. elegans. We provide evidence that the
      regulation of histone acetylation requires CRA-1, a NatB domain-containing
      protein homologous to human NAA25, which controls the levels of acetyl-Coenzyme A
      (acetyl-CoA) by antagonizing ACER-1, a previously unknown and conserved acetyl
      CoA hydrolase. CRA-1 is in turn negatively regulated by XND-1, an AT-hook
      containing protein. We propose that this newly defined protein network links
      acetyl-CoA metabolism to meiotic DSB formation via modulation of global histone
      acetylation. 

PMID- 25768303
TI  - Modulation effect of interlayer spacing on the superconductivity of electron
      doped FeSe-based intercalates.
AB  - FeSe-based intercalates are regarded as promising candidates for high-critical
      temperature (Tc) superconductors. Here we present new Na- and Sr-intercalated
      FeSe superconductors with embedded linear diamines (H2N)CnH2n(NH2) (abbreviated
      as DA; n = 0, 2, 3, or 6) prepared using a low-temperature ammonothermal method
      to investigate the effect of interlayer spacing on the superconductivity of
      electron-doped FeSes. The embedded DA formed a monolayer or bilayer in the
      interlayer of FeSe. The interlayer spacing between nearest FeSe layers could be
      tuned from 0.87 to 1.14 nm without significant change in the Na/Sr content or the
      ratio of Fe to Se. Importantly, bilayer phases Na/ethylenediamine- and
      Sr/hydrazine-FeSe show improved structural stability compared to that of Na/NH3
      FeSe. The series of Na- and Sr-intercalated FeSe samples exhibited nearly the
      same high Tc values of 41-46 and 34-38 K, respectively, irrespective of rather
      different interlayer spacing d. The peculiar insensitivity for both series can be
      ascribed to the negligible dispersions of bands along the c axis; i.e., Fermi
      surfaces are nearly two-dimensional when d is larger than a certain threshold
      value (dsat) of ~0.9 nm. The Fermi surface shape is already optimal for Tc, and a
      larger d will not enhance Tc further. On the other hand, the difference in Tc
      between two series may be explained by the higher carrier doping level in Na/DA
      FeSes compared to that in Sr/DA-FeSes, resulting in the increased density of
      states at the Fermi level and superconducting pairing strength. 

PMID- 25768304
TI  - Correction: attributions of cancer 'alarm' symptoms in a community sample.

PMID- 25768305
TI  - Climate envelope modeling and dispersal simulations show little risk of range
      extension of the Shipworm, Teredo navalis (L.), in the Baltic sea.
AB  - The shipworm, Teredo navalis, is absent from most of the Baltic Sea. In the last
      20 years, increased frequency of T. navalis has been reported along the southern
      Baltic Sea coasts of Denmark, Germany, and Sweden, indicating possible range
      extensions into previously unoccupied areas. We evaluated the effects of
      historical and projected near-future changes in salinity, temperature, and oxygen
      on the risk of spread of T. navalis in the Baltic. Specifically, we developed a
      simple, GIS-based, mechanistic climate envelope model to predict the spatial
      distribution of favourable conditions for adult reproduction and larval
      metamorphosis of T. navalis, based on published environmental tolerances to these
      factors. In addition, we used a high-resolution three-dimensional hydrographic
      model to simulate the probability of spread of T. navalis larvae within the study
      area. Climate envelope modeling showed that projected near-future climate change
      is not likely to change the overall distribution of T. navalis in the region, but
      will prolong the breeding season and increase the risk of shipworm establishment
      at the margins of the current range. Dispersal simulations indicated that the
      majority of larvae were philopatric, but those that spread over a wider area
      typically spread to areas unfavourable for their survival. Overall, therefore, we
      found no substantive evidence for climate-change related shifts in the
      distribution of T. navalis in the Baltic Sea, and no evidence for increased risk
      of spread in the near-future. 

PMID- 25768307
TI  - Impedimetric transduction of swelling in pH-responsive hydrogels.
AB  - A pH-responsive hydrogel composed of an aliphatic diamine cross-linked with
      polyethylene glycol diglycidyl ether (PEGDGE) using a single, rapid
      polymerisation step has been used to detect glucose by entrapping glucose oxidase
      (GOx) within its cationic network. The swelling response of hydrogel disks on
      exposure to glucose were optimised through variation of factors including the
      cross-linking density of the network, GOx loading and the addition of catalase.
      Hydrogel-modified carbon cloth electrodes were also prepared and characterised
      using voltammetric and impedimetric techniques. Non-faradaic electrochemical
      impedance spectroscopy (EIS) and gravimetry were both employed to track the
      swelling response of the gels quantitatively. The clear potential of utilising
      impedance to transduce hydrogel swelling was demonstrated where a linear decrease
      in gel resistance (Rgel) corresponding to the swelling response was observed in
      the range 1 to 100 MUM. A dramatic increase in the limit of detection of six
      orders of magnitude over the gravimetric measurement was achieved (from 0.33 mM
      to 0.08 MUM). This increased sensitivity, coupled with the textile-based
      electrode substrate approach opens the potential applicability of this system for
      monitoring glucose concentration via the skin by sweat or interstitial fluid
      (ISF). 

PMID- 25768306
TI  - A naturally occurring null variant of the NMDA type glutamate receptor NR3B
      subunit is a risk factor of schizophrenia.
AB  - Hypofunction of the N-methyl-D-aspartate type glutamate receptor (NMDAR) has been
      implicated in the pathogenesis of schizophrenia. Here, we investigated the
      significance of a common human genetic variation of the NMDAR NR3B subunit that
      inserts 4 bases within the coding region (insCGTT) in the pathogenesis of
      schizophrenia. The cDNA carrying this polymorphism generates a truncated protein,
      which is electrophysiologically non-functional in heterologous expression
      systems. Among 586 schizophrenia patients and 754 healthy controls, insCGTT was
      significantly overrepresented in patients compared to controls (odds ratio =
      1.37, p = 0.035). Among 121 schizophrenia patients and 372 healthy controls,
      genetic analyses of normal individuals revealed that those carrying insCGTT have
      a predisposition to schizotypal personality traits (F1,356 = 4.69, p = 0.031).
      Furthermore, pre-pulse inhibition, a neurobiological trait disturbed in patients
      with schizophrenia, was significantly impaired in patients carrying insCGTT
      compared with those with the major allele (F1,116 = 5.72, p = 0.018, F1,238 =
      4.46, p = 0.036, respectively). These results indicate that a naturally occurring
      null variant in NR3B could be a risk factor of schizophrenia. 

PMID- 25768308
TI  - Vitronectin expression in the airways of subjects with asthma and chronic
      obstructive pulmonary disease.
AB  - Vitronectin, a multifunctional glycoprotein, is involved in coagulation,
      inhibition of the formation of the membrane attack complex (MAC), cell adhesion
      and migration, wound healing, and tissue remodeling. The primary cellular source
      of vitronectin is hepatocytes; it is not known whether resident cells of airways
      produce vitronectin, even though the glycoprotein has been found in exhaled
      breath condensate and bronchoalveolar lavage from healthy subjects and patients
      with interstitial lung disease. It is also not known whether vitronectin
      expression is altered in subjects with asthma and COPD. In this study, bronchial
      tissue from 7 asthmatic, 10 COPD and 14 control subjects was obtained at autopsy
      and analyzed by immunohistochemistry to determine the percent area of submucosal
      glands occupied by vitronectin. In a separate set of experiments, quantitative
      colocalization analysis was performed on tracheobronchial tissue sections
      obtained from donor lungs (6 asthmatics, 4 COPD and 7 controls). Vitronectin RNA
      and protein expressions in bronchial surface epithelium were examined in 12
      subjects who undertook diagnostic bronchoscopy. Vitronectin was found in the
      tracheobronchial epithelium from asthmatic, COPD, and control subjects, although
      its expression was significantly lower in the asthmatic group. Colocalization
      analysis of 3D confocal images indicates that vitronectin is expressed in the
      glandular serous epithelial cells and in respiratory surface epithelial cells
      other than goblet cells. Expression of the 65-kDa vitronectin isoform was lower
      in bronchial surface epithelium from the diseased subjects. The cause for the
      decreased vitronectin expression in asthma is not clear, however, the reduced
      concentration of vitronectin in the epithelial/submucosal layer of airways may be
      linked to airway remodeling. 

PMID- 25768311
TI  - Dynamic self-assembly of colloids through periodic variation of inter-particle
      potentials.
AB  - A short-ranged and time-varying attraction drives self-assembly of colloidal
      crystals from a suspension of colloidal spheres. Brownian dynamics simulations of
      this process demonstrate that the envelope for self-assembly of large, low defect
      crystals is broadened dramatically when this attractive interaction is switched
      on and off periodically in time. This process is termed dynamic self-assembly
      because temporal control of the inter-particle potential requires injection and
      extraction of energy from the self-assembling materials. We develop a theory
      using non-equilibrium statistical mechanics to determine the rate at which
      particles cross a similarly switched energy barrier, and show that there is a
      switching rate that maximizes barrier crossing. While barrier crossing towards
      thermodynamic equilibrium is limited by the Kramers hopping rate, the rate of out
      of-equilibrium barrier crossing can exceed this limit. In the context of self
      assembly, barrier crossing is the rate limiting step and responsible for both
      defect formation and slow nucleation. This simple theory is used to explain the
      optimal switching rate observed in our simulations of dynamic self-assembly.
      Dynamic self-assembly via switched potentials enables growth of ordered phases
      without thermodynamic constraints on the assembly kinetics. 

PMID- 25768310
TI  - A dual radiolabelling approach for tracking metal complexes: investigating the
      speciation of copper bis(thiosemicarbazonates) in vitro and in vivo.
AB  - Copper(II)bis(thiosemicarbazonato) complexes such as [(64)Cu]Cu-ATSM continue to
      be investigated for positron emission tomography (PET) imaging of tumour hypoxia.
      However, the currently proposed mechanisms for the mode of action of these
      complexes are unable to account fully for their observed biological behaviour. In
      order to examine the roles of the copper metal and the ligand, we designed a pair
      of (123)I/(64)Cu-copper bis(thiosemicarbazonates), radiolabelled at either the
      metal or at the ligand. In vitro cellular retention studies of the orthogonal
      pair demonstrate for the first time that retention under hypoxia involves
      dissociation of the copper bis(thiosemicarbazone) complex, consistent with the
      previously suggested mechanism of reductive trapping of copper. In contrast, in
      vivo biodistribution and dynamic PET/SPECT imaging of the orthogonally labelled
      complexes underline our previous findings for [(64)Cu]Cu-ATSM and [(64)Cu]Cu
      acetate, providing further support for the important contribution of copper
      metabolism in the in vivo hypoxia selectivity of Cu-ATSM. This dual
      radiolabelling approach may find applications for determining the speciation of
      other metal complexes in vitro and in vivo.

PMID- 25768309
TI  - Variation in honey bee gut microbial diversity affected by ontogenetic stage, age
      and geographic location.
AB  - Social honey bees, Apis mellifera, host a set of distinct microbiota, which is
      similar across the continents and various honey bee species. Some of these
      bacteria, such as lactobacilli, have been linked to immunity and defence against
      pathogens. Pathogen defence is crucial, particularly in larval stages, as many
      pathogens affect the brood. However, information on larval microbiota is
      conflicting. Seven developmental stages and drones were sampled from 3 colonies
      at each of the 4 geographic locations of A. mellifera carnica, and the samples
      were maintained separately for analysis. We analysed the variation and abundance
      of important bacterial groups and taxa in the collected bees. Major bacterial
      groups were evaluated over the entire life of honey bee individuals, where
      digestive tracts of same aged bees were sampled in the course of time. The
      results showed that the microbial tract of 6-day-old 5th instar larvae were
      nearly equally rich in total microbial counts per total digestive tract weight as
      foraging bees, showing a high percentage of various lactobacilli (Firmicutes) and
      Gilliamella apicola (Gammaproteobacteria 1). However, during pupation, microbial
      counts were significantly reduced but recovered quickly by 6 days post-emergence.
      Between emergence and day 6, imago reached the highest counts of Firmicutes and
      Gammaproteobacteria, which then gradually declined with bee age. Redundancy
      analysis conducted using denaturing gradient gel electrophoresis identified
      bacterial species that were characteristic of each developmental stage. The
      results suggest that 3-day 4th instar larvae contain low microbial counts that
      increase 2-fold by day 6 and then decrease during pupation. Microbial succession
      of the imago begins soon after emergence. We found that bacterial counts do not
      show only yearly cycles within a colony, but vary on the individual level.
      Sampling and pooling adult bees or 6th day larvae may lead to high errors and
      variability, as both of these stages may be undergoing dynamic succession. 

PMID- 25768312
TI  - Palladium-meta-terarylphosphine catalyst for the Mizoroki-Heck reaction of
      (hetero)aryl bromides and functional olefins.
AB  - The evolutionary meta-terarylphosphine ligand architecture of Cy*Phine was
      recently shown to be a key feature that imposed outstanding performance in
      palladium-catalyzed copper-free Sonogashira applications. Herein, the Pd-Cy*Phine
      combination has similarly proven to be a powerful catalyst system for the
      Mizoroki-Heck reaction. Using high-throughput screening (HTS) methodology, DMF
      and NaHCO3 were rapidly identified as the most effective solvent and base pair
      for the cross-coupling catalysis of challenging and industrially valuable
      substrates including highly electron-rich heteroaryl bromides and unactivated
      olefins. Unprotected functional groups were well tolerated using low catalyst
      loadings, and the simple protocol produced excellent yields (up to 99%) with
      unprecedented substrate diversity. The Pd-Cy*Phine system broadly outperformed
      many state-of-the-art commercial alternatives, which demonstrated its potential
      as a next-generation cross-coupling catalyst. 

PMID- 25768313
TI  - Electrochromic graphene molecules.
AB  - Polyclic aromatic hydrocarbons also called Graphene Molecules (GMs), with
      chemical composition C132H36(COOH)2 were synthesized in situ on the surface of
      transparent nanocrystalline indium tin oxide (nc-ITO) electrodes and their
      electronic structure was studied electrochemically and spectro-electrochemically.
      Variations in the potential applied onto the nc-ITO/GM electrodes induce only
      small changes in the observed current, but they produce dramatic changes in the
      absorption of the GMs, which are associated with their oxidation and reduction.
      Analysis of the absorption changes using a modified Nernst equation is used to
      determine standard potentials associated with the individual charge transfer
      processes. For the GMs prepared here, these were found to be E1,ox(0) = 0.77 +/-
      0.01 V and E2,ox(0) = 1.24 +/- 0.02 V vs NHE for the first and second oxidation
      and E1,red(0) = -1.50 +/- 0.04 V for the first reduction. The charge transfer
      processes are found to be nonideal. The nonideality factors associated with the
      oxidation and reduction processes are attributed to strong interactions between
      the GM redox centers. Under the conditions of potential cycling, GMs show rapid
      (seconds) color change with high contrast and stability. An electrochromic
      application is demonstrated wherein the GMs are used as the optically active
      component. 

PMID- 25768314
TI  - Atmospheric processes and their controlling influence on cloud condensation
      nuclei activity.

PMID- 25768315
TI  - Correction to "Investigation of the structure of ethanol-water mixtures by
      molecular dynamics simulation I: analyses concerning the hydrogen-bonded pairs".

PMID- 25768316
TI  - Pseudoendogenous presence of beta-boldenone sulphate and glucuronide in untreated
      young bulls from the food chain.
AB  - The administration of boldenone (bold) to bovines, either for growth promotion or
      therapeutic purposes, has been banned in the EU since 1981. It is, however, a
      pseudoendogenous hormone, thus its detection in bovine urine, in the form of
      alpha-boldenone conjugates, is considered fully compliant up to 2 ng ml(-1).
      Greater attention has been placed on beta-boldenone, the anabolic active epimer,
      whose conjugated form must be absent in urine. Recently, the identification of a
      biomarker representing unquestionable evidence of illicit treatment with bold or
      its precursor androstadienedione has been a major topic in the literature
      regarding the detection of residues in bovine urine, and beta-boldenone sulphate
      is a candidate molecule. In this study, we used a method previously validated
      according to the European Commission Decision 2002/657/EC for the determination
      of sulphate and glucuronide conjugates of beta-boldenone. We assessed the
      occurrence of these molecules in young bull urine, with the aim of understanding
      whether they could be of endogenous origin, and to check for a possible
      relationship with particular environmental and stress conditions. Urine samples
      from 56 young bulls were collected after transport stress, under non-stressful
      conditions and after transport and slaughter stress. Histopathological
      investigation of the hormone target organs, i.e. the bulbourethral and prostate
      glands, was also performed. The results indicate an inverse relationship between
      the presence and concentration of beta-boldenone sulpho- and gluco-conjugates in
      urine, and stress conditions, expressed by the absence of detection at the
      slaughterhouse. No significant macroscopic and histologic lesions were detected.
      Our study indicates that beta-boldenone sulphate could be a biomarker of
      treatment only at the slaughterhouse, while at the farm, in untreated animals
      (i.e. after a five-month period under the control of Official Veterinarians),
      sulphate and glucuronide metabolites were found with a frequency of 78% and 46%,
      respectively, showing the endogenous origin of boldenone. 

PMID- 25768318
TI  - Tumori Journal, 2015 and beyond: the right time for a change.

PMID- 25768317
TI  - Efficacy and safety of stereotactic ablative radiotherapy in patients with
      previous pneumonectomy.
AB  - BACKGROUND: Thoracic surgery for a newly diagnosed primary lung tumor following a
      previous pneumonectomy is rarely indicated. Stereotactic ablative radiotherapy
      (SABR) might represent a curative option. This report focuses on outcomes,
      toxicity and quality of life (QoL) after SABR. METHODS: Nine patients were
      treated with SABR between 2004 and 2011; median time since surgery was 8.4 years.
      In 4 cases, a histological confirmation was possible with bronchoscopy. In 5
      cases, the clinical proof of malignancy was based on radiological criteria.
      Forced expiratory volume in 1 second (FEV1) and diffusing capacity of the lung
      for carbon monoxide (DLCO) were tested in all patients. A SABR biologically
      equivalent dose of >100 Gy was prescribed in all cases. QoL questionnaire forms
      were administered before SABR and during follow-up. RESULTS: Median follow-up was
      41.8 months. We did not observe grade >=3 acute toxicity, and concerning late
      toxicity, we registered 2 cases. QoL was decreased during the first 12 months of
      follow-up, followed by a progressive improvement after this time. One patient had
      a local relapse at 7.4 years; 1 developed a new nodule at 5.5 years, associated
      with metastases; and 1 developed a new nodule without any systemic disease at 3
      years. There were 2 cancer-related deaths (18.2%) at 3 and 12 months after
      progression. CONCLUSIONS: Data support efficacy and safety of SABR in patients
      with a new primary lung cancer following previous pneumonectomy, with acceptable
      acute, late toxicity profile and without significant impairment of QoL. Our
      results were comparable to those in the literature.

PMID- 25768319
TI  - Quality of life and cosmesis after breast cancer: whole breast radiotherapy vs
      partial breast high-dose-rate brachytherapy.
AB  - AIM AND BACKGROUND: Conservative surgery and radiotherapy for early breast cancer
      offers a better quality of life than mastectomy. As 80-85% of breast relapses
      develop close to the tumour bed, partial breast irradiation was developed to
      overcome drawbacks with standard radiotherapy. This study compares quality of
      life and cosmesis after partial breast multi-catheter high-dose rate interstitial
      brachytherapy or standard radiotherapy. METHODS: A questionnaire, exploring body
      image, fear of recurrence, satisfaction with treatment and cosmesis, was
      administered to 39 partial and 78 whole breast patients at a median of 20 and 80
      months after radiotherapy. Patients' and physicians' cosmetic assessments were
      compared. RESULTS: Groups were well-matched, except for: a higher percentage of
      chemotherapy-treated patients in the whole breast group and a older median age
      and a higher percentage of infiltrating ductal carcinoma G1 in partial breast
      group. At first and second analysis no significant inter-group difference emerged
      on body image and fear of recurrence, while partial breast patients were more
      satisfied with cosmetic outcome and at first analysis with treatment. Comparing
      results from first and second analysis into each treatment group, body image was
      significantly better at the first analysis in both groups. Fear of recurrence was
      unchanged. No differences were found in cosmesis as assessed by patients. At
      first and second analyses physicians' assessment of cosmesis was significantly
      better in the partial breast group. CONCLUSIONS: Even at longer follow-up,
      quality of life is similar after partial or whole breast irradiation. Cosmesis is
      better after partial breast irradiation.

PMID- 25768320
TI  - Identification of hepatocellular carcinoma-associated hub genes and pathways by
      integrated microarray analysis.
AB  - AIMS AND BACKGROUND: Hepatocellular carcinoma (HCC) is a dismal malignancy
      associated with multiple molecular changes. The purpose of this study was to
      identify the differentially expressed genes and analyze the biological processes
      related to HCC. METHODS AND STUDY DESIGN: Datasets of HCC were obtained from the
      NCBI Gene Expression Omnibus. Integrated analysis of differentially expressed
      genes was performed using the INMEX program. Then Gene Ontology enrichment
      analyses and pathway analysis were performed based on the Gene Ontology website
      and Kyoto Encyclopedia of Genes and Genomes. A protein-protein interaction
      network was constructed using the Cytoscape software; the netwerk served to find
      hub genes for HCC. Real-time RT-PCR was used to validate the microarray data for
      hub genes. RESULTS: We identified 273 genes that were differentially expressed in
      HCC. Gene Ontology enrichment analyses revealed response to cadmium ion, cellular
      response to cadmium ion, and cellular response to zinc ion for these genes.
      Pathway analysis showed that significant pathways included fatty acid metabolism,
      butanoate metabolism, and PPAR signaling pathway. The protein-protein interaction
      network indicated that CDH1, ECHS1, ACAA1, MT2A, and MYC were important genes
      which participated in many interactions. Experimental validation of the role of
      four upregulated genes (ECHS1, ACAA1, MT2A and MYC) in the progression of HCC was
      carried out. CONCLUSIONS: Our study displayed genes that were consistently
      differentially expressed in HCC. The biological pathways and protein-protein
      interaction networks associated with those genes were also identified. We
      predicted that CDH1, ECHS1, ACAA1, MT2A, and MYC might be target genes for
      diagnosing HCC.

PMID- 25768321
TI  - Outcomes of trimodality approach in the management of T2N0M0 bladder cancer.
AB  - AIMS AND BACKGROUND: The main objective of this study is to evaluate outcomes of
      bladder preservation treatment for patients with muscle-invasive bladder cancer.
      METHODS AND STUDY DESIGN: 38 patients with histologically proven muscle-invasive
      bladder cancer treated at our department between January 2008 and December 2013
      were analyzed retrospectively. Age, gender, pathology, stage, 3-year overall
      survival, 3-year disease-free survival, radiotherapy (RT) dose, genitourinary and
      gastrointestinal toxicity scores and response evaluation of the patients were
      recorded. 3-year overall survival and 3-year disease-free survivals were
      calculated by Kaplan-Meier method along with the analysis of gender, pathology,
      stage and therapy response of the study group. RESULTS: 33 patients (86.8%) were
      managed with concomitant chemoradiotherapy whereas 5 patients (13.2%) received
      only radiation therapy due to renal insufficency and comorbid diseases. 6 (15.8%)
      out of 38 patients had partial response (PR) and remaining 32 (84.2%) patients
      experienced complete response (CR). The PR group underwent salvage cystectomy and
      CR group had been followed-up after radical radiotherapy. Mean age of the group
      was 70.9 (range 45-90) years. 26 of all patients were male (68.4%) and 12 were
      female (31.6%). Mean follow-up time after completion of radiotherapy was 24.7
      months (range 12-40). Mean RT dose was 64 Gy (range 60-66). 3-year overall
      survival was 64% and 3-year disease free survival was 73%. CONCLUSIONS: Bladder
      preserving approach is an alternative definitive therapy solution to radical
      cystectomy in the treatment of muscle-invasive bladder cancer with less
      morbidity, preserved natural bladder, and high quality of life.

PMID- 25768325
TI  - Social media and medical education: Exploring the potential of Twitter as a
      learning tool.
AB  - This study set out to explore the ways in which social media can facilitate
      learning in medical education. In particular we were interested in determining
      whether the use of Twitter during an academic conference can promote learning for
      participants. The Twitter transcript from the annual International Conference on
      Residency Education (ICRE) 2013 was qualitatively analysed for evidence of the
      three overarching cognitive themes: (1) preconceptions, (2) frameworks, and (3)
      metacognition/refl ection in regard to the National Research Council ' s (NRC)
      How People Learn framework . Content analysis of the Twitter transcript revealed
      evidence of the three cognitive themes as related to how people learn. Twitter
      appears to be most effective at stimulating individuals ' preconceptions, thereby
      engaging them with the new material acquired during a medical education
      conference. The study of social media data, such as the Twitter data used in this
      study, is in its infancy. Having established that Twitter does hold signifi cant
      potential as a learning tool during an academic conference, we are now in a
      better position to more closely examine the spread, depth, and sustainability of
      such learning during medical education meetings.

PMID- 25768323
TI  - The extent and consequences of p-hacking in science.
AB  - A focus on novel, confirmatory, and statistically significant results leads to
      substantial bias in the scientific literature. One type of bias, known as "p
      hacking," occurs when researchers collect or select data or statistical analyses
      until nonsignificant results become significant. Here, we use text-mining to
      demonstrate that p-hacking is widespread throughout science. We then illustrate
      how one can test for p-hacking when performing a meta-analysis and show that,
      while p-hacking is probably common, its effect seems to be weak relative to the
      real effect sizes being measured. This result suggests that p-hacking probably
      does not drastically alter scientific consensuses drawn from meta-analyses. 

PMID- 25768324
TI  - What are the potential benefits of using proton therapy in Taiwanese cancer
      patients?
AB  - The potential benefits of proton therapy have been established in pediatric
      cancer, skull base tumor, uveal melanoma, and other types of cancers. Western and
      Asian countries, however, have differences in the pattern of cancer incidence;
      this leads to the difference in patient demographics for proton therapy.
      Furthermore, the advancement of the scanning beam technique in proton therapy
      greatly expands the capability of proton therapy in disease sites with great
      complexity. In this review, we focus on the cancers with high incidence in
      Taiwan, based on the Cancer Registry Annual Report, 2011, Taiwan. The potential
      case number and clinical benefits from proton therapy are evaluated and
      discussed. Two endemic cancers, hepatocellular carcinoma and head and neck
      cancer, are considered to be the major disease types appropriate for proton
      therapy in Taiwan. Primary lung cancer and left side breast cancer, which are
      popular in western countries as well as in Taiwan, are included for discussion.
      The issue of cost-effectiveness for proton therapy is also reviewed. Finally, we
      point out the clinical trials that should be conducted for proton therapy in
      Taiwan. 

PMID- 25768326
TI  - Routine outcome measurement in Australia.
AB  - Australia has been implementing routine outcome measurement in its specialized
      public sector mental health services for over a decade. It uses a range of
      clinician-rated and consumer-rated measures that are administered at set times
      during episodes of inpatient, ambulatory and community residential episodes of
      care. Routine outcome measurement is now embedded in service delivery, and data
      are made available in a variety of ways to different audiences. These data are
      used by policy-makers and planners to inform decisions about system-wide reforms,
      by service managers to monitor quality and effectiveness, and by clinicians to
      guide clinical decision-making and to promote dialogue with consumers. Consumers,
      carers and the general community can use these data to ensure that services are
      accountable for the care they deliver. This paper describes the status quo in
      Australia with respect to routine outcome measurement, discusses the factors that
      led to its successful implementation, and considers the steps that are necessary
      for its continued development. 

PMID- 25768327
TI  - Benign Solid Thyroid Nodules: US-guided High-Intensity Focused Ultrasound
      Ablation-Initial Clinical Outcomes.
AB  - PURPOSE: To assess the short-term efficacy and safety of ultrasonographically
      (US)-guided high-intensity focused ultrasound (HIFU) ablation for treatment of
      benign solid thyroid nodules. MATERIALS AND METHODS: This prospective study was
      approved by the institutional ethics committee, and written informed consent was
      acquired. HIFU ablation was performed in one session with US guidance and
      conscious sedation in 20 euthyroid patients (mean age, 44.5 years) with a benign
      solitary or dominant thyroid nodule. Thyroid nodule volume, US structure, and
      Doppler pattern were assessed at baseline, at 1 week, and at 1, 3, and 6 months
      after treatment. Adverse events associated with HIFU were evaluated. Statistical
      analysis was conducted by using repeated measures analysis of variance, the
      Student t test, chi(2) test, and correlation analysis. RESULTS: The mean +/-
      standard deviation nodule volume was 4.96 mL +/- 2.79 at the start of the study.
      Nodule volume had decreased to 3.05 mL +/- 1.96 at the 3-month follow-up
      examination (n = 20, P < .001), and reached 2.91 mL +/- 2.43 by the 6-month
      follow-up examination (n = 16, P < .001). By then, the mean volume reduction was
      48.7% +/- 24.3 (P < .001). Isoechoic nodules showed greater reduction at 1 month
      than did hypoechoic nodules (31.6% +/- 18.1 vs 16.4% +/- 8.6, P = .053). Nodules
      with markedly increased blood flow showed smaller volume reduction at 3 months
      than did less-vascularized nodules (10.9% +/- 14.5 vs 41.5% +/- 20.3, P = .054).
      Minor transient complications (eg, subcutaneous edema, mild skin redness) were
      observed in two patients. CONCLUSION: Early data suggest that US-guided HIFU
      ablation is an effective and safe procedure for treatment of benign solid thyroid
      nodules. Initial US echogenicity and vascularization influence the ablation
      outcome.

PMID- 25768328
TI  - Re-do craniotomy for recurrent glioblastoma.

PMID- 25768330
TI  - Dendritic cell immunotherapy for solid tumors: evaluation of the DCVax(r)
      platform in the treatment of glioblastoma multiforme.
AB  - DCVax((r)) (Northwest Biotherapeutics, Inc., MD, USA) is a platform technology
      for delivering dendritic cell based therapeutic vaccines for a variety of
      cancers, including glioblastoma multiforme (GBM). DCVax((r))-L, one of the
      implementations of the DCVax platform, provides personalized active immunotherapy
      composed of autologous dendritic cells pulsed with autologous whole tumor lysate.
      Clinical trials with DCVax-L for GBM included previous Phase I/II clinical trials
      and an ongoing Phase III trial. Preliminary reports of patient outcomes after
      administration of the DCVax-L vaccine provide a promising therapeutic paradigm
      for patients with both initially diagnosed and recurrent GBM. Here we evaluate
      the current literature and clinical experience with the DCVax platform, with a
      particular focus on GBM treatment.

PMID- 25768331
TI  - Depression screening in patients with brain tumors: a review.
AB  - Brain tumor (BT) is often a devastating disease associated with poor prognosis.
      Depression is a common complication in BT patients that often remains under
      recognized and untreated. Implementation of reliable depression screening
      algorithms in routine neuro-oncology setting could potentially improve
      recognition of depression. The Hospital Anxiety and Depression scale-Depression
      subscale and Patient Health Questionnaire-9 demonstrated adequate psychometric
      properties for depressive disorder screening in glioma patients. Patients
      screened positive for depression should be referred for detailed psychiatric
      assessment prior to initiating anti-depressive treatment. Further
      methodologically rigorous studies investigating psychometric properties of single
      item and multiple-item depression scales are urgently warranted. Studies
      evaluating anti-depressive treatments' efficacy and clinical value of depression
      biomarkers are important avenues for future research endeavors in BT patients.

PMID- 25768332
TI  - Medulloblastoma development: tumor biology informs treatment decisions.
AB  - Medulloblastoma is the most common malignant pediatric brain tumor. Current
      treatments including surgery, craniospinal radiation and high-dose chemotherapy
      have led to improvement in survival. However, the risk for recurrence as well as
      significant long-term neurocognitive and endocrine sequelae associated with
      current treatment modalities underscore the urgent need for novel tumor-specific,
      normal brain-sparing therapies. It has also provided the impetus for research
      focused on providing a better understanding of medulloblastoma biology. The
      expectation is that such studies will lead to the identification of new
      therapeutic targets and eventually to an increase in personalized treatment
      approaches.

PMID- 25768333
TI  - Treating recurrent glioblastoma: an update.
AB  - Glioblastoma, the most aggressive of the gliomas, has a high recurrence and
      mortality rate. The nature of this poor prognosis resides in the molecular
      heterogeneity and phenotypic features of this tumor. Despite research advances in
      understanding the molecular biology, it has been difficult to translate this
      knowledge into effective treatment. Nearly all will have tumor recurrence, yet to
      date very few therapies have established efficacy as salvage regimens. This
      challenge is further complicated by imaging confounders and to an even greater
      degree by the ever increasing molecular heterogeneity that is thought to be both
      sporadic and treatment-induced. The development of novel clinical trial designs
      to support the development and testing of novel treatment regimens and drug
      delivery strategies underscore the need for more precise techniques in imaging
      and better surrogate markers to help determine treatment response. This review
      summarizes recent approaches to treat patients with recurrent glioblastoma and
      considers future perspectives.

PMID- 25768335
TI  - Laparoscopic choledochojejunostomy in various hepatobiliary and pancreatic
      surgeries: a single surgeon's experience.
AB  - BACKGROUND: The aims of this study were to measure the learning curve for
      laparoscopic choledochojejunostomy (LCJ), to describe the technical tips and to
      report the follow-up data. MATERIALS AND METHODS: The results of LCJ performed on
      84 patients were analyzed. Patients were divided into eight groups, by surgical
      order. The plateau of the learning curve was defined as the period during which
      the operative time showed a dramatic decrease. The exact operative time was
      recorded using video analysis. RESULTS: Compared with the first three groups, the
      fourth group showed a significantly shorter LCJ time. The subsequent groups
      showed a plateau, indicating that there were no more significant changes in the
      LCJ time. After the plateau of the learning curve was reached, the average LCJ
      time was 27.4+/-4.7 minutes. Six cases of postoperative bile leakage occurred,
      with all occurring before the plateau of the learning curve was reached. Five of
      the 6 cases of bile leakage had a nondilated common bile duct. CONCLUSIONS: Even
      for a surgeon experienced in laparoscopic surgery, there is a steep learning
      curve for the performance of LCJ. With careful video review, education of the
      surgical team, and various technical tips, the learning curve can be shortened.
      After the learning curve, experienced surgeons can perform LCJ with acceptable
      results.

PMID- 25768334
TI  - Stereotactic radiosurgery of glomus jugulare tumors: current concepts, recent
      advances and future perspectives.
AB  - Stereotactic radiosurgery (SRS), a very highly focused form of therapeutic
      irradiation, has been widely recognized as a viable treatment option in the
      management of intracranial pathologies including benign tumors, malign tumors,
      vascular malformations and functional disorders. The applications of SRS are
      continuously expanding thanks to the ever-increasing advances and corresponding
      improvements in neuroimaging, radiation treatment techniques, equipment,
      treatment planning and delivery systems. In the context of glomus jugulare tumors
      (GJT), SRS is being more increasingly used both as the upfront management
      modality or as a complementary or salvage treatment option. As its safety and
      efficacy is being evident with compiling data from studies with longer follow-up
      durations, SRS appears to take the lead in the management of most patients with
      GJT. Herein, we address current concepts, recent advances and future perspectives
      in SRS of GJT in light of the literature.

PMID- 25768336
TI  - Consolidation of novel word learning in native English-speaking adults.
AB  - Sleep has been shown to improve the retention of newly learned words. However,
      most methodologies have used artificial or foreign language stimuli, with
      learning limited to word/novel word or word/image pairs. Such stimuli differ from
      many word-learning scenarios in which definition strings are learned with novel
      words. Thus, we examined sleep's benefit on learning new words within a native
      language by using very low-frequency words. Participants learned 45 low-frequency
      English words and, at subsequent recall, attempted to recall the words when given
      the corresponding definitions. Participants either learned in the morning with
      recall in the evening (wake group), or learned in the evening with recall the
      following morning (sleep group). Performance change across the delay was
      significantly better in the sleep than the wake group. Additionally, the
      Levenshtein distance, a measure of correctness of the typed word compared with
      the target word, became significantly worse following wake, whereas sleep
      protected correctness of recall. Polysomnographic data from a subsample of
      participants suggested that rapid eye movement (REM) sleep may be particularly
      important for this benefit. These results lend further support for sleep's
      function on semantic learning even for word/definition pairs within a native
      language. 

PMID- 25768337
TI  - A meta-analysis comparing 18F-FLT PET with 18F-FDG PET for assessment of brain
      tumor recurrence.
AB  - OBJECTIVE: The purpose of this systematic meta-analysis was to evaluate the
      diagnostic accuracy of 3'-deoxy-3'-(18)F-fluorothymidine ((18)F-FLT) PET for the
      assessment of glioma recurrence and compare it with that of (18)F
      fluorodeoxyglucose ((18)F-FDG) PET. METHODS: The authors electronically and
      manually searched for studies from 1948 to 2014 that evaluated the diagnostic
      accuracy of (18)F-FDG or (18)F-FLT PET for glioma recurrence. The primary results
      of sensitivity, specificity, and diagnostic odds ratio (DOR) were summarized
      using the random-effects model. Summary receiver operating characteristic (ROC)
      curves and its area under the curve (AUC were used to summarize the overall
      diagnostic accuracy. Statistical analysis was performed with the software STATA
      (version 11.0). RESULTS: Twenty-four studies that included a total of 799
      patients were included in the meta-analysis. The pooled sensitivity, specificity,
      DOR, and summary ROC AUC for the overall diagnostic accuracy of (18)F-FDG PET
      were 0.78 (95% CI 0.69-0.85), 0.77 (95% CI 0.66-0.85), 12 (95% CI 6-22), and 0.84
      (95% CI 0.81-0.87), respectively. The pooled sensitivity, specificity, DOR, and
      summary ROC AUC for the overall diagnostic accuracy of (18)F-FLT PET were 0.82
      (95% CI 0.51-0.95), 0.76 (95% CI 0.50-0.91), 15 (95% CI 4-56), and 0.85 (95% CI
      0.81-0.88), respectively. Metaregression analysis showed that year of
      publication, male proportion, average age, and blinding review did not affect the
      test performance statistically significantly (all P > 0.05). CONCLUSION: This
      meta-analysis indicates that PET by using (18)F-FLT has a moderately better
      overall accuracy for diagnosing glioma recurrence compared with that by using
      (18)F-FDG. Video abstract: http://links.lww.com/NMC/A41.

PMID- 25768338
TI  - Three-dimensional cell culture: a breakthrough in vivo.
AB  - Cell culture is an important tool for biological research. Two-dimensional cell
      culture has been used for some time now, but growing cells in flat layers on
      plastic surfaces does not accurately model the in vivo state. As compared to the
      two-dimensional case, the three-dimensional (3D) cell culture allows biological
      cells to grow or interact with their surroundings in all three dimensions thanks
      to an artificial environment. Cells grown in a 3D model have proven to be more
      physiologically relevant and showed improvements in several studies of biological
      mechanisms like: cell number monitoring, viability, morphology, proliferation,
      differentiation, response to stimuli, migration and invasion of tumor cells into
      surrounding tissues, angiogenesis stimulation and immune system evasion, drug
      metabolism, gene expression and protein synthesis, general cell function and in
      vivo relevance. 3D culture models succeed thanks to technological advances,
      including materials science, cell biology and bioreactor design. 

PMID- 25768340
TI  - Palmitoylethanolamide inhibits glutamate release in rat cerebrocortical nerve
      terminals.
AB  - The effect of palmitoylethanolamide (PEA), an endogenous fatty acid amide
      displaying neuroprotective actions, on glutamate release from rat cerebrocortical
      nerve terminals (synaptosomes) was investigated. PEA inhibited the Ca2+-dependent
      release of glutamate, which was triggered by exposing synaptosomes to the
      potassium channel blocker 4-aminopyridine. This release inhibition was
      concentration dependent, associated with a reduction in cytosolic Ca2+
      concentration, and not due to a change in synaptosomal membrane potential. The
      glutamate release-inhibiting effect of PEA was prevented by the Ca(v)2.1 (P/Q
      type) channel blocker omega-agatoxin IVA or the protein kinase A inhibitor H89,
      not affected by the intracellular Ca2+ release inhibitors dantrolene and
      CGP37157, and partially antagonized by the cannabinoid CB1 receptor antagonist
      AM281. Based on these results, we suggest that PEA exerts its presynaptic
      inhibition, likely through a reduction in the Ca2+ influx mediated by Ca(v)2.1
      (P/Q-type) channels, thereby inhibiting the release of glutamate from rat
      cortical nerve terminals. This release inhibition might be linked to the
      activation of presynaptic cannabinoid CB1 receptors and the suppression of the
      protein kinase A pathway.

PMID- 25768341
TI  - Regulatory effects of caffeic acid phenethyl ester on neuroinflammation in
      microglial cells.
AB  - Microglial activation has been widely demonstrated to mediate inflammatory
      processes that are crucial in several neurodegenerative disorders.
      Pharmaceuticals that can deliver direct inhibitory effects on microglia are
      therefore considered as a potential strategy to counter balance neurodegenerative
      progression. Caffeic acid phenethyl ester (CAPE), a natural phenol in honeybee
      propolis, is known to possess antioxidant, anti-inflammatory and anti-microbial
      properties. Accordingly, the current study intended to probe the effects of CAPE
      on microglia activation by using in vitro and in vivo models. Western blot and
      Griess reaction assay revealed CAPE significantly inhibited the expressions of
      inducible nitric oxide synthase (NOS), cyclooxygenase (COX)-2 and the production
      of nitric oxide (NO). Administration of CAPE resulted in increased expressions of
      hemeoxygenase (HO)-1and erythropoietin (EPO) in microglia. The phosphorylated
      adenosine monophosphate-activated protein kinase (AMPK)-alpha was further found
      to regulate the anti-inflammatory effects of caffeic acid. In vivo results from
      immunohistochemistry along with rotarod test also revealed the anti
      neuroinflammatory effects of CAPE in microglia activation. The current study has
      evidenced several possible molecular determinants, AMPKalpha, EPO, and HO-1, in
      mediating anti-neuroinflammatory responses in microglial cells. 

PMID- 25768342
TI  - Extracellular production of a novel endo-beta-agarase AgaA from Pseudomonas
      vesicularis MA103 that cleaves agarose into neoagarotetraose and neoagarohexaose.
AB  - The gene agaA, of the isolated marine bacterium Pseudomonas vesicularis MA103,
      comprised 2958-bp nucleotides encoding a putative agarase AgaA of 985 amino
      acids, which was predicted to contain a signal peptide of 29 amino acids in the N
      terminus, a catalytic domain of glycoside hydrolase 16 (GH16) family, a bacterial
      immunoglobulin group 2 (Big 2), and three carbohydrate binding modules 6 (CBM 6).
      The gene agaA was cloned and overexpressed in Escherichia coli, and the optimum
      temperatures for AgaA overexpression were 16, 20 and 24  degrees C. The agaA was
      cloned without its signal peptide for cytosolic production overexpression,
      whereas it was cloned with the heterologous signal peptide PelB and its
      endogenous signal peptide for periplasmic and extracellular productions,
      respectively. Extracellular and periplasmic rAgaA showed greater activity than
      that of cytosolic rAgaA, indicating that membrane translocation of AgaA may
      encourage proper protein folding. Time-course hydrolysis of agarose by rAgaA was
      accomplished and the products were analyzed using thin layer chromatography and
      matrix-assisted laser desorption inoization-time of flight mass spectrometry,
      indicating that AgaA from P. vesicularis was an endo-type beta-1,4 agarase that
      cleaved agarose into neoagarotetraose and neoagarohexaose as the final products. 

PMID- 25768339
TI  - Mechanisms by which different functional states of mitochondria define yeast
      longevity.
AB  - Mitochondrial functionality is vital to organismal physiology. A body of evidence
      supports the notion that an age-related progressive decline in mitochondrial
      function is a hallmark of cellular and organismal aging in evolutionarily distant
      eukaryotes. Studies of the baker's yeast Saccharomyces cerevisiae, a unicellular
      eukaryote, have led to discoveries of genes, signaling pathways and chemical
      compounds that modulate longevity-defining cellular processes in eukaryotic
      organisms across phyla. These studies have provided deep insights into
      mechanistic links that exist between different traits of mitochondrial
      functionality and cellular aging. The molecular mechanisms underlying the
      essential role of mitochondria as signaling organelles in yeast aging have begun
      to emerge. In this review, we discuss recent progress in understanding mechanisms
      by which different functional states of mitochondria define yeast longevity,
      outline the most important unanswered questions and suggest directions for future
      research. 

PMID- 25768343
TI  - Effects of ration levels on growth and reproduction from larvae to first-time
      spawning in the female Gambusia affinis.
AB  - Somatic growth and reproduction were examined in individual laboratory-grown
      female Gambusia affinis fed with high (H), medium (M) and low (L) ration levels
      from birth to the first-time spawning. Results showed that the body length and
      weight, condition factor (CF), wet weight gain (WG(w)), specific growth rate in
      wet weight (SGR(w)) and ration levels in terms of energy (RL(e)) decreased
      significantly (p < 0.05) with decreasing ration levels from birth to first-time
      spawning. On the contrary, the food conversion efficiency in terms of energy
      (FCE(e)) increased significantly (p < 0.05) with the decreasing ration levels
      from birth to first-time sexual maturity. Furthermore, higher percentages of
      energy intake from food were allocated to somatic and gonad growth in M and L
      groups compared to the H group before sexual maturity; In addition, the time for
      first-time spawning in groups M and L was longer than that of the H group. As a
      result, the gonad-somatic index (GSI) and oocytes/embryos weight in M and L
      groups were similar to that of the H group, although the ovary weight and
      oocytes/embryos numbers were all lower than that of the H group. Also, similar
      growth performances were observed in second-generation offspring, which were
      produced by female parents fed with different ration levels. These findings
      suggest that the female G. affinis could produce a number of healthy offspring
      under conditions of food restriction, and that this could be achieved by
      increasing the energy allocated to gonad development, reducing fecundity and
      delaying spawning time. These life strategies ensured that G. affinis could
      survive and thrive in adverse environmental conditions and exhibit
      characteristics of invasive fish species.

PMID- 25768344
TI  - PEDF improves cardiac function in rats with acute myocardial infarction via
      inhibiting vascular permeability and cardiomyocyte apoptosis.
AB  - Pigment epithelium-derived factor (PEDF) is a pleiotropic gene with anti
      inflammatory, antioxidant and anti-angiogenic properties. However, recent reports
      about the effects of PEDF on cardiomyocytes are controversial, and it is not
      known whether and how PEDF acts to inhibit hypoxic or ischemic endothelial injury
      in the heart. In the present study, adult Sprague-Dawley rat models of acute
      myocardial infarction (AMI) were surgically established. PEDF-small interfering
      RNA (siRNA)-lentivirus (PEDF-RNAi-LV) or PEDF-LV was delivered into the
      myocardium along the infarct border to knockdown or overexpress PEDF,
      respectively. Vascular permeability, cardiomyocyte apoptosis, myocardial infarct
      size and animal cardiac function were analyzed. We also evaluated PEDF's effect
      on the suppression of the endothelial permeability and cardiomyocyte apoptosis
      under hypoxia in vitro. The results indicated that PEDF significantly suppressed
      the vascular permeability and inhibited hypoxia-induced endothelial permeability
      through PPARgamma-dependent tight junction (TJ) production. PEDF protected
      cardiomyocytes against ischemia or hypoxia-induced cell apoptosis both in vivo
      and in vitro via preventing the activation of caspase-3. We also found that PEDF
      significantly reduced myocardial infarct size and enhanced cardiac function in
      rats with AMI. These data suggest that PEDF could protect cardiac function from
      ischemic injury, at least by means of reducing vascular permeability,
      cardiomyocyte apoptosis and myocardial infarct size. 

PMID- 25768346
TI  - Novel cholesterol-based cationic lipids as transfecting agents of DNA for
      efficient gene delivery.
AB  - The design, synthesis and biological evaluation of the cationic lipid gene
      delivery vectors based on cholesterol and natural amino acids lysine or histidine
      are described. Cationic liposomes composed of the newly synthesized cationic
      lipids 1a or 1b and neutral lipid DOPE (1,2-dioleoyl-L-alpha-glycero-3
      phosphatidyl-ethanolamine) exhibited good transfection efficiency. pEGFP-N1
      plasmid DNA was transferred into 293T cells by cationic liposomes formed from
      cationic lipids 1a and 1b, and the transfection activity of the cationic lipids
      was superior (1a) or parallel (1b) to that of the commercially available 3beta-[N
      (N',N'-dimethylaminoethyl)-carbamoyl] cholesterol (DC-Chol) derived from the same
      cholesterol backbone with different head groups. Combined with the results of
      agarose gel electrophoresis, transfection experiments with various molar ratios
      of the cationic lipids and DOPE and N/P (+/-) molar charge ratios, a more
      effective formulation was formed, which could lead to relatively high
      transfection efficiency. Cationic lipid 1a represents a potential agent for the
      liposome used in gene delivery due to low cytotoxicity and impressive gene
      transfection activity.

PMID- 25768345
TI  - Molecular mechanisms underlying beta-adrenergic receptor-mediated cross-talk
      between sympathetic neurons and immune cells.
AB  - Cross-talk between the sympathetic nervous system (SNS) and immune system is
      vital for health and well-being. Infection, tissue injury and inflammation raise
      firing rates of sympathetic nerves, increasing their release of norepinephrine
      (NE) in lymphoid organs and tissues. NE stimulation of beta2-adrenergic receptors
      (ARs) in immune cells activates the cAMP-protein kinase A (PKA) intracellular
      signaling pathway, a pathway that interfaces with other signaling pathways that
      regulate proliferation, differentiation, maturation and effector functions in
      immune cells. Immune-SNS cross-talk is required to maintain homeostasis under
      normal conditions, to develop an immune response of appropriate magnitude after
      injury or immune challenge, and subsequently restore homeostasis. Typically,
      beta2-AR-induced cAMP is immunosuppressive. However, many studies report actions
      of beta2-AR stimulation in immune cells that are inconsistent with typical cAMP
      PKA signal transduction. Research during the last decade in non-immune organs,
      has unveiled novel alternative signaling mechanisms induced by beta2-AR
      activation, such as a signaling switch from cAMP-PKA to mitogen-activated protein
      kinase (MAPK) pathways. If alternative signaling occurs in immune cells, it may
      explain inconsistent findings of sympathetic regulation of immune function. Here,
      we review beta2-AR signaling, assess the available evidence for alternative
      signaling in immune cells, and provide insight into the circumstances necessary
      for "signal switching" in immune cells. 

PMID- 25768349
TI  - Prognosis and psychosocial outcomes of attempted suicide by early adolescence: a
      6-year follow-up of school students into early adulthood.
AB  - Adulthood psychiatric and psychosocial outcomes of early adolescence suicidal
      acts were studied. A representative sample of school adolescents (T1, mean age,
      13.7 years; n = 2464; 50.8% female; 88.3% participation) was followed up a year
      later with the same questionnaire (T2). High scorers of depression were matched
      with low or moderate scorers and interviewed using the Kiddie-Schedule for
      Affective Disorders and Schizophrenia-Present and Lifetime version (mean age,
      14.9 years; n = 345; 94% participation). They were reassessed after 5 years (T3,
      mean age, 20.0 years; n = 242; 73% participation). Those who attempted suicide
      before the age of 14 years and repeated suicidal acts between ages 14 and 15
      years had worser prognostic profiles than incident cases between ages 14 and 15
      years. Male attempters had better psychiatric prognosis than female attempters.
      Attempters were more likely to have contacted child protection services but not
      mental health services. Clinicians need to be aware of long-term pervasive
      outcomes of adolescent suicidality. 

PMID- 25768350
TI  - You tell me.

PMID- 25768348
TI  - Whole exome sequencing for a patient with Rubinstein-Taybi syndrome reveals de
      novo variants besides an overt CREBBP mutation.
AB  - Rubinstein-Taybi syndrome (RSTS) is a rare condition with a prevalence of 1 in
      125,000-720,000 births and characterized by clinical features that include
      facial, dental, and limb dysmorphology and growth retardation. Most cases of RSTS
      occur sporadically and are caused by de novo mutations. Cytogenetic or molecular
      abnormalities are detected in only 55% of RSTS cases. Previous genetic studies
      have yielded inconsistent results due to the variety of methods used for genetic
      analysis. The purpose of this study was to use whole exome sequencing (WES) to
      evaluate the genetic causes of RSTS in a young girl presenting with an Autism
      phenotype. We used the Autism diagnostic observation schedule (ADOS) and Autism
      diagnostic interview revised (ADI-R) to confirm her diagnosis of Autism. In
      addition, various questionnaires were used to evaluate other psychiatric
      features. We used WES to analyze the DNA sequences of the patient and her parents
      and to search for de novo variants. The patient showed all the typical features
      of Autism, WES revealed a de novo frameshift mutation in CREBBP and de novo
      sequence variants in TNC and IGFALS genes. Mutations in the CREBBP gene have been
      extensively reported in RSTS patients, while potential missense mutations in TNC
      and IGFALS genes have not previously been associated with RSTS. The TNC and
      IGFALS genes are involved in central nervous system development and growth. It is
      possible for patients with RSTS to have additional de novo variants that could
      account for previously unexplained phenotypes. 

PMID- 25768347
TI  - Coupling and coordination in gene expression processes with pre-mRNA splicing.
AB  - A processing is a tightly regulated and highly complex pathway which includes
      transcription, splicing, editing, transportation, translation and degradation. It
      has been well-documented that splicing of RNA polymerase II medicated nascent
      transcripts occurs co-transcriptionally and is functionally coupled to other RNA
      processing. Recently, increasing experimental evidence indicated that pre-mRNA
      splicing influences RNA degradation and vice versa. In this review, we summarized
      the recent findings demonstrating the coupling of these two processes. In
      addition, we highlighted the importance of splicing in the production of intronic
      miRNA and circular RNAs, and hence the discovery of the novel mechanisms in the
      regulation of gene expression. 

PMID- 25768351
TI  - How much more intelligent do we have to be about the burden of severe sepsis and
      septic shock?

PMID- 25768352
TI  - Early noninvasive detection of hypovolemia in trauma patients--are we there yet?

PMID- 25768353
TI  - Bespoke end-of-life decision making in ICU: has the tailor got the right
      measurements?

PMID- 25768354
TI  - Systemic antibiotics and respiratory tract colonization in critically ill
      patients: an unfinished story.

PMID- 25768355
TI  - Applied physiology and process of care for patients with acute respiratory
      distress syndrome.

PMID- 25768356
TI  - Hypothalamo-pituitary-adrenal axis dynamics: do apples and oranges increase our
      understanding of the hypothalamo-pituitary-adrenal axis in illness?

PMID- 25768357
TI  - Prehospital aspirin use and acute respiratory distress syndrome--a case for
      aspirin in the drinking water?

PMID- 25768358
TI  - Can we really predict morbidity and mortality in burn patients?

PMID- 25768359
TI  - I'm okay, you're not okay: moral distress in health care as an issue of affective
      perspective taking and in-group/out-group tensions.

PMID- 25768360
TI  - Ultrasound-guided vascular access in critical care: can a choice of real-time
      imaging axis view overcome the "curse of dimensionality"?

PMID- 25768361
TI  - Compressing the chest: are we on target?

PMID- 25768362
TI  - New application of a traditional vasoactive agent, sodium nitroprusside, in
      targeted temperature management during cardiac arrest and resuscitation.

PMID- 25768363
TI  - Get out of bed: immobility in the neurologic ICU.

PMID- 25768364
TI  - The evidence is in: noninvasive ventilation saves lives.

PMID- 25768365
TI  - Can we improve outcomes by using active compression-decompression and impedance
      threshold devices during resuscitation?

PMID- 25768366
TI  - Influenza and other respiratory viruses are underdiagnosed in critically ill
      patients.

PMID- 25768367
TI  - The authors reply.

PMID- 25768368
TI  - Withdrawal on ICU: when is the point of cardiac death?

PMID- 25768369
TI  - The authors reply.

PMID- 25768370
TI  - Neurologic assessment of comatose survivors of cardiac arrest: the details
      matter.

PMID- 25768371
TI  - The authors reply.

PMID- 25768372
TI  - What's new in Shock? April 2015.

PMID- 25768373
TI  - Angiotensin-converting enzyme inhibition attenuates lipopolysaccharide-induced
      lung injury by regulating the balance between angiotensin-converting enzyme and
      angiotensin-converting enzyme 2 and inhibiting mitogen-activated protein kinase
      activation.
AB  - Activation of the renin-angiotensin system (angiotensin-converting enzyme
      [ACE]/angiotensin II [Ang II] and angiotensin-converting enzyme 2 [ACE2]/Ang-1-7)
      has been implicated in the pathophysiology of inflammatory response and acute
      lung injury (ALI). Previous studies have shown that the ACE inhibitor captopril
      (Cap) may be a potent therapeutic drug for ALI. However, the mechanisms of its
      protective effects on ALI are still largely unknown. In this study, we evaluated
      the effects of Cap on preventing lipopolysaccharide (LPS)-induced lung injury and
      further investigated the underlying mechanisms of these protective effects. Rats
      were intraperitoneally pretreated with Cap (50 mg/kg) 30 min prior to an
      intravenous administration of LPS (7.5 mg/kg). Furthermore, following a 30-min
      pretreatment with Cap (10 mol/mL) or combined with the ACE2 inhibitor MLN4760 (10
      mol/mL), rat pulmonary microvascular endothelial cells (PMVECs) were stimulated
      with LPS (1 mg/mL). Captopril pretreatment significantly attenuated LPS-induced
      pathophysiological changes in the lung, inhibited secretion of tumor necrosis
      factor alpha and interleukin 6, reduced the ratio of Ang II to Ang-1-7, and
      reversed the increased ratio of ACE to ACE2, which was remarkably decreased from
      7.07 (LPS only) to 1.71 (LPS + Cap). The protective effects of Cap on ALI were
      also confirmed by in vitro studies, in which Cap suppressed LPS-induced secretion
      of proinflammatory cytokines and modulated the expression levels of ACE and ACE2.
      After Cap pretreatment, the ratio of ACE to ACE2 expression was remarkably
      decreased from 5.18 (LPS alone) to 1.52 (LPS + Cap). Furthermore, Cap given
      before LPS administration led to inhibition of p38 mitogen-activated protein
      kinase (MAPK), ERK (extracellular signal-regulated kinase) 1/2, and JNK (c-Jun N
      terminal kinase) phosphorylation in PMVECs, whereas MLN4760 abolished the
      protective effects of Cap on LPS-induced secretion of proinflammatory cytokines
      and abolished Cap-induced blockade of p38MAPK, ERK1/2, and JNK phosphorylation.
      Our findings reveal that Cap exerts protective effects on LPS-induced lung injury
      and the cytotoxicity of PMVECs, and these effects may, at least in part, regulate
      the balance of ACE and ACE2 expression and inhibit the activation of MAPKs. 

PMID- 25768374
TI  - Implementing refinements in preclinical sepsis modeling: walking a fine line
      between what ethics condones and the gaping investigative holes call for.

PMID- 25768375
TI  - Tocilizumab as an Adjuvant Therapy for Hemophagocytic Lymphohistiocytosis
      Associated With Visceral Leishmaniasis.
AB  - Leishmaniasis is important as a cause of hemophagocytic lymphohistiocytosis (HLH)
      and must be considered and excluded in patients with HLH because it can cause
      severe or even fatal complications. When HLH is present, there is a deficient
      downregulation of the immune response, leading to an uncontrolled inflammation.
      We report a case of visceral leishmaniasis-HLH where the therapy with
      tocilizumab, targeting interleukin 6, help to regulate the immune response for
      the infection of Leishmania. 

PMID- 25768376
TI  - Safety and Efficacy of Rocuronium With Sugammadex Reversal Versus Succinylcholine
      in Outpatient Surgery-A Multicenter, Randomized, Safety Assessor-Blinded Trial.
AB  - Complex surgical procedures are increasingly performed in an outpatient setting,
      with emphasis on rapid recovery and case turnover. In this study, the combination
      of rocuronium for neuromuscular blockade (NMB) reversed by single-dose sugammadex
      was compared with succinylcholine followed by spontaneous recovery in outpatient
      surgery. This multicenter, randomized, safety assessor-blinded study enrolled
      adults undergoing a short elective outpatient surgical procedure requiring NMB
      and tracheal intubation. Patients were randomized to NMB with either rocuronium
      0.6 mg/kg for tracheal intubation with incremental doses of rocuronium 0.15 mg/kg
      and subsequent reversal with sugammadex 4.0 mg/kg at 1-2 posttetanic counts or
      succinylcholine 1.0 mg/kg for intubation with spontaneous recovery. The primary
      efficacy end point was the time from sugammadex administration to recovery of the
      train-of-four ratio to 0.9; for succinylcholine, time from administration to
      recovery of the first twitch (T1) to 90% was assessed. From 167 patients
      enrolled, 150 received treatment. The all-subjects-treated population comprised
      70 patients in the rocuronium-sugammadex group and 80 in the succinylcholine
      group. Geometric mean (95% confidence interval) time from the start of sugammadex
      administration to recovery of the train-of-four ratio to 0.9 was 1.8 (1.6-2.0)
      minutes. Geometric mean (95% confidence interval) time from succinylcholine
      administration to recovery of T1 to 90% was 10.8 (10.1-11.5) minutes. Health
      outcome variables were similar between the groups. Adverse events were reported
      in 87.1% and 93.8% of patients for rocuronium-sugammadex and succinylcholine,
      respectively. In conclusion, rocuronium for intubation followed by sugammadex for
      reversal of NMB offers a viable treatment option in outpatient surgery without
      prolonging recovery duration or jeopardizing safety.

PMID- 25768377
TI  - Assessment of steady-state clopidogrel reactivity by using platelet reactivity
      units.
AB  - Platelet function testing is an important laboratory measure in clopidogrel
      treatment. We sought to investigate the stability of the reactivity of
      clopidogrel after 1 month of treatment. A prospective analysis was carried out
      using a matched study design to compare platelet reactivity units (PRUs) and
      platelet inhibition in clopidogrel-treated patients. Patients with various
      cardiac diseases were divided into 2 matched groups. The first group was treated
      on an inpatient acute basis, and the other group was treated on an outpatient
      chronic basis. PRU was measured 5 days after clopidogrel administration in the
      acute group and 1 month after chronic use for several cardiac indications in the
      second group. VerifyNow (Accumetrics) was used to detect platelet reactivity and
      calculate inhibition rates in response to clopidogrel. A total of 260 Saudi
      patients were enrolled, including 90 inpatients and 170 outpatients. A
      significant difference was observed in PRU (173.69 vs. 195) and percent
      inhibition (24.05% vs. 16.13%) between the outpatient and inpatient groups.
      Platelet function evolves over time and initial readings may not be constant.

PMID- 25768378
TI  - Efficacy of Continuous Positive Airway Pressure in the Treatment of Chronic
      Obstructive Pulmonary Disease Combined With Respiratory Failure.
AB  - Our aim is to investigate the efficacy of continuous positive airway pressure
      (CPAP) in chronic obstructive pulmonary disease (COPD) combined with respiratory
      failure. Electronic and manual searches were applied to retrieve published
      studies relevant to CPAP, COPD, and respiratory failure. The retrieved studies
      were screened based on stringent inclusion and exclusion criteria to identify
      high-quality clinical studies for meta-analysis. Comprehensive meta-analysis 2.0
      was conducted to statistical analysis. Initially, we retrieved 958 studies based
      on stringent inclusion and exclusion criteria, 10 studies, containing a total of
      372 patients with COPD combined with respiratory failure, were selected for meta
      analysis. The result of our meta-analysis revealed that partial pressure of
      carbon dioxide (PaCO2) in patients with COPD combined with respiratory failure
      was significantly lower 24 hours after CPAP treatment, and partial pressure of
      oxygen (PaO2) and pH were markedly higher 24 hours after CPAP treatment in the
      same patient group, indicating statistically significant differences as a result
      of CPAP treatment. Subgroup analysis based on ethnicity demonstrated that PaCO2
      in patients with COPD combined with respiratory failure is evidently lower 24
      hours after CPAP treatment among whites, but no such statistical correlation was
      observed among Asians. The results of this meta-analysis indicate that CPAP can
      effectively improve the respiratory function of patients with COPD combined with
      respiratory failure, and CPAP can be an effective way of treating COPD. 

PMID- 25768379
TI  - Tranexamic Acid Treatment Decreases Hidden Blood Loss in Total Knee Arthroplasty.
AB  - The aim of our meta-analysis is to investigate the effect of tranexamic acid
      (TXA) on hidden blood loss (HBL) in total knee arthroplasty (TKA). A literature
      search was undertaken to identify all cohort studies that investigated the effect
      of TXA on HBL in TKA. Both electronic database search and manual search were used
      to retrieve studies related to the topic, and the retrieved studies were screened
      according to our stringent inclusion and exclusion criteria. Comprehensive Meta
      analysis 2.0 software (CMA 2.0) was used for statistical analysis of the data
      retrieved from selected case-cohort studies. A total of 480 studies were
      initially retrieved, and after further screening and selection, 7 studies were
      eventually incorporated into our meta-analysis. The 7 studies included a total of
      530 osteoarthritis or rheumatic arthritis patients who had TKA, and among them,
      250 patients received an intravenous injection of TXA as cases and 280 patients
      received an intravenous injection of sodium chloride as sterile placebo controls.
      Our meta-analysis revealed that the volume of HBL of cases was lower than that of
      controls, which was statistically significant. The ethnicity-stratified analysis
      suggested that the volume of HBL of cases was significantly lower than that of
      controls in both the Asians and whites, also at statistically significant levels.
      Our meta-analysis provides strong evidence that TXA significantly reduces HBL in
      TKA, thus TXA can be used as a standard drug to prevent/reduce HBL in TKA.

PMID- 25768381
TI  - Farewell from Daniel M. Corcos, Editor-in-Chief Emeritus.

PMID- 25768380
TI  - Comparison of Treatment Outcomes of Different Spermatic Vein Ligation Procedures
      in Varicocele Treatment.
AB  - In this study, 4 different spermatic vein ligation procedures for varicocele (VC)
      treatment were compared based on recurrence rate, postoperative complications,
      and semen quality. Between January 2012 and May 2013, a total of 345 male
      patients with VC were recruited at The First Affiliated Hospital of Soochow
      University. Patients were performed by different ligation procedures, and they
      were divided into 4 groups: laparoscopic varicocelectomy group (LV group: n =
      84), microscopic inguinal varicocelectomy group (MIV group: n = 85), microscopic
      retroperitoneal varicocelectomy group (MRV group: n = 86), and microscopic
      subinguinal varicocelectomy group (MSV group: n = 90). In MSV group, the
      operative time was 55 +/- 6.9 minutes, which was significantly longer than LV,
      MIV, and MRV groups (P < 0.05). Recurrence rate in LV group was at 11.9%, the
      highest rate observed compared with the MIV, MRV, and MSV groups (P < 0.05).
      Scrotal edema and testicular atrophy in MSV group were markedly decreased (P <
      0.05), and scrotal pain was relieved in almost all patients in the MSV group at a
      significantly higher rate than LV, MIV, and MRV groups (P < 0.05). Sperm
      concentration, sperm count of grades a + b, and sperm motility (%) in the MSV
      group were sharply higher than LV, MIV, and MRV groups (all P < 0.05). Our study
      indicates that MSV is the most beneficial of the 4 spermatic vein ligation
      procedures and may be offered as the first-line treatment for VC in infertile
      men.

PMID- 25768382
TI  - Thank you to Dr. Daniel M. Corcos.

PMID- 25768383
TI  - Treating mood disorders in patients with a history of intestinal surgery: a
      systematic review.
AB  - Bariatric surgery is increasingly being performed, with the intended benefits of
      significant and durable weight loss. Radical surgical resection can result in
      short bowel syndrome (SBS), a rare and devastating condition. Psychological
      distress is common in these patients. Relevant articles were identified by
      searching Pubmed and EMBASE databases with the following keywords:
      'Bariatrics'[Mesh] OR 'Short Bowel Syndrome' AND 'Antidepressive Agents' OR
      'Psychotropic Drugs'[Mesh]. One in-vitro study, four clinical studies and six
      relevant case reports were identified. Most clinical studies on antidepressant
      focused on the Roux-en-Y gastric bypass (RYGB); these results are somewhat
      conflicting for a variety of reasons including different methodologies and small
      sample sizes. One month after RYGB, in patients receiving serotonin or
      serotonin/noradrenaline reuptake inhibitors, antidepressant levels decrease to
      50% of preoperative levels and return to baseline (or greater) by 6 months in
      almost all patients. Other pharmacokinetic studies have shown that, 1 year after
      RYGB, duloxetine and sertraline levels are significantly reduced in comparison
      with the control population. Paradoxically, in patients with SBS and a few years
      after surgery, high concentration to dose ratios have been reported for
      citalopram and escitalopram; this may be because of an intestinal adaptation.
      Surgery of the intestine is likely to modify absorption and first-pass metabolism
      of drugs; managing the treatment of depression and anxiety in bariatric and SBS
      patients therefore presents a major challenge. Close clinical follow-up,
      associated with therapeutic drug monitoring when available, should enable the
      optimization of treatment response and modulate the risk of adverse events.

PMID- 25768384
TI  - Fast and enhanced broadband photoresponse of a ZnO nanowire array/reduced
      graphene oxide film hybrid photodetector from the visible to the near-infrared
      range.
AB  - In the present work, a ZnO nanowire array/reduced graphene oxide film hybrid
      nanostructure was realized, and the photovoltaic responses from the visible to
      the near-infrared range were investigated. Compared with the pure ZnO nanowire
      array and rGO thin film, the hybrid composite exhibited a fast and greatly
      enhanced broadband photovoltaic response that resulted from the formation of
      interfacial Schottky junctions between ZnO and rGO. 

PMID- 25768385
TI  - Riboflavin-UV--a crosslinking for fixation of biosynthetic corneal collagen
      implants.
AB  - PURPOSE: To evaluate riboflavin-UV-A crosslinking as an alternative suture-free
      fixation method for biosynthetic corneal collagen implants. METHODS: A range of
      cell-free corneal implants consisting of recombinant human collagen type III were
      examined. In vitro, the implants were crosslinked with different riboflavin
      solutions and irradiations. Ex vivo, the biosynthetic corneal implants were
      placed on the anterior cornea of porcine and rabbit eyes after performing deep
      anterior lamellar keratoplasty with a trephine, femtosecond laser, or excimer
      laser. UV-A crosslinking was performed with isotonic or hypotonic riboflavin at
      either standard or rapid procedure. The corneas were excised, fixed in PFA 4%,
      and embedded in paraffin. Crosslinking effects on the implants and the adhesion
      between implant and corneal bed were evaluated by slit-lamp biomicroscopy,
      optical coherence tomography (OCT) images, and histologically. RESULTS: After the
      crosslinking procedure, the implants showed different degrees of thinning. The
      accuracy of cutting the corneal bed was highest with the excimer laser. Good
      adhesion of the implant in the corneal bed could be demonstrated in OCT images.
      This was more accurate in porcine eyes than in rabbit eyes. Histologically,
      crosslinks between implant and corneal stroma were demonstrated. There was no
      difference between standard and rapid crosslinking procedures. CONCLUSIONS:
      Riboflavin-UV-A crosslinking as a fixation method for biosynthetic corneal
      collagen implants was demonstrated to be promising. It can reduce suture-related
      complications such as haze formation and surface irregularity. Stability of the
      implants, especially shrinkage after riboflavin-UV-A crosslinking, needs to be
      further evaluated. Biostability, integration, and long-term outcome are further
      evaluated in in vivo animal experiments.

PMID- 25768386
TI  - Monitoring corneal densities following primary pterygium excision with adjuvant
      topical mitomycin-C application--an observational study of corneal scar changes.
AB  - PURPOSE: Corneal densitometry is an inherent feature of the Pentacam device. We
      aim to assess the changes in corneal scar density with serial Scheimpflug images
      following primary pterygium excision with topical application of mitomycin-C.
      METHODS: We recruited patients who underwent primary, single-headed pterygium
      excision with topical adjuvant mitomycin-C. Scheimpflug images were taken at
      postoperative weeks 1, 4, and 12, and all patients received topical
      corticosteroid and antibiotic treatment for at least 4 weeks postoperatively.
      Corneal scar densities were generated by the software for analysis. Secondary
      outcome measures included intraocular pressures and pterygium recurrence at the
      end of 12 weeks. Changes in corneal densities between weeks 12, 4, and 1 were
      calculated. RESULTS: We recruited 31 eyes of 31 patients, of whom 16 were male
      patients and 15 were female patients, with 19 left and 12 right eyes. Mean age at
      operation was 62.0 +/- 9.4 years. Mean reduction in density of the anterior 120
      MUm of cornea was -3.07 [95% confidence interval (CI), -6.600 to 0.460] and 
      3.455 (95% CI, -6.787 to -0.122) at postoperative 4 and 12 weeks, respectively,
      and mean reduction percentage was -4.7% (95% CI, -10.7% to 1.3%) and -6.3% (95%
      CI, -11.8% to -0.7%), respectively. No steroid response or pterygium recurrence
      was reported. CONCLUSIONS: Corneal densitometry is an objective measure to detect
      scar changes in zones and layers. The overall reduction of density was evident at
      12 weeks postoperatively. These results might serve as baseline figures for
      future studies in assessing modulation of corneal scars over time.

PMID- 25768387
TI  - Reproducibility of dynamic Scheimpflug-based pneumotonometer and its correlation
      with a dynamic bidirectional pneumotonometry device: methodological issues.

PMID- 25768388
TI  - Using Photovoice with youth to develop a drug prevention program in a rural
      Hawaiian community.
AB  - INTRODUCTION: Substance use represents a significant and persistent health
      disparity among Native Hawaiian youth and communities. A community-university
      participatory action research project was conducted to develop a Native Hawaiian
      model of drug prevention. METHODS: Ten youth participated in eight Photovoice
      focus groups. Focus group transcripts and the youths' SHOWED (see, happening,
      our, why, empower, do) worksheets were analyzed. RESULTS: Emergent analyses are
      described regarding focus group theme identification and the meaning of each
      theme. Youth-selected exemplary photographs and researcher-selected exemplary
      quotations are provided. IMPLICATIONS: Native Hawaiian drug prevention will be
      place-based in culturally significant community locations, experiential, and
      guided by multigenerational teaching and learning.

PMID- 25768389
TI  - The influence of an Alaska Native accent and reputation on perceived therapist
      credibility.
AB  - In this study, we examined the influence of an Alaska Native (AN) accent and
      reputation on perceived therapist credibility after controlling for universal
      diverse orientation. Participants listened to and rated therapist audio
      recordings that differed in AN accent (strong, minimal) and reputational cues
      (expert, recent graduate, student). While credibility ratings of the accent
      conditions did not differ in the expert and recent graduate scenarios, the
      graduate student therapist was seen as less attractive and useful when she spoke
      with a strong accent. 

PMID- 25768391
TI  - Latent class analysis of substance use and aggressive behavior in reservation
      based American Indian youth who attempted suicide.
AB  - American Indian (AI) adolescents who attempt suicide are heterogeneous. A latent
      class analysis was used to identify subgroups of reservation-based AI adolescents
      with recent suicide attempts. Indicators of class membership were substance abuse
      and aggressive behaviors; clinical correlates of subgroup membership included
      risky sexual behavior and recent exposure to suicidal behavior. Three subgroups
      were identified, representing low, medium, and high substance use and aggressive
      behavior. Suicide exposure was associated with membership in the lowest risk
      behavior subgroup; risky sexual behavior was associated with membership the
      highest risk behaviors subgroup. Findings suggest a continuum of risk behaviors
      in reservation-based AI youth who attempt suicide.

PMID- 25768392
TI  - Listening Comprehension in Middle-Aged Adults.
AB  - PURPOSE: The purpose of this summary is to examine changes in listening
      comprehension across the adult lifespan and to identify factors associated with
      individual differences in listening comprehension. METHOD: In this article, the
      author reports on both cross-sectional and longitudinal changes in listening
      comprehension. CONCLUSIONS: Despite significant declines in both sensory and
      cognitive abilities, listening comprehension remains relatively unchanged in
      middle-aged listeners (between the ages of 40 and 60 years) compared with young
      listeners. These results are discussed with respect to possible compensatory
      factors that maintain listening comprehension despite impaired hearing and
      reduced cognitive capacities.

PMID- 25768390
TI  - Healing of the canoe: preliminary results of a culturally tailored intervention
      to prevent substance abuse and promote tribal identity for Native youth in two
      Pacific Northwest tribes.
AB  - Using Community-based and Tribal Participatory Research (CBPR/TPR) approaches, an
      academic-tribal partnership between the University of Washington Alcohol and Drug
      Abuse Institute and the Suquamish and Port Gamble S'Klallam Tribes developed a
      culturally grounded social skills intervention to promote increased cultural
      belonging and prevent substance abuse among tribal youth. Participation in the
      intervention, which used the Canoe Journey as a metaphor for life, was associated
      with increased hope, optimism, and self-efficacy and with reduced substance use,
      as well as with higher levels of cultural identity and knowledge about alcohol
      and drugs among high school-age tribal youth. These results provide preliminary
      support for the intervention curricula in promoting positive youth development,
      an optimistic future orientation, and the reduction of substance use among Native
      youth. 

PMID- 25768393
TI  - A dimension map for molecular aggregates.
AB  - A pair of gyradius ratios, defined from the principal radii of gyration, are used
      to generate a dimension map that describes the geometry of molecular aggregates
      in water and in organic solvents. Molecular dynamics simulations were performed
      on the aggregation of representative biomolecules and polyaromatic compounds to
      demonstrate application of the dimension map. It was shown that molecular
      aggregate data on the dimension map were bounded by two boundary curves, and that
      the map could be separated into three regions representing three groups of
      structures: one-dimensional rod-like structures; two-dimensional planar
      structures or short-cylinder-like structures; and three-dimensional sphere-like
      structures. Examining the location of the aggregates on the dimension map and how
      the location changes with solvent type and solute material parameter provides a
      simple yet effective way to infer the aggregation manner and to study solubility
      and mechanism of aggregation. 

PMID- 25768394
TI  - Gelatin embedding: a novel way to preserve biological samples for terahertz
      imaging and spectroscopy.
AB  - Sample dehydration has traditionally been a challenging problem in ex vivo
      terahertz biomedical experiments as water content changes significantly affect
      the terahertz properties and can diminish important contrast features. In this
      paper, we propose a novel method to prevent sample dehydration using gelatin
      embedding. By looking at terahertz image data and calculating the optical
      properties of the gelatin-embedded sample, we find that our method successfully
      preserves the sample for at least 35 h, both for imaging and spectroscopy. Our
      novel preservation method demonstrates for the first time the capability to
      simultaneously maintain sample structural integrity and prevent dehydration at
      room temperature. This is particularly relevant for terahertz studies of freshly
      excised tissues but could be beneficial for other imaging and spectroscopy
      techniques. 

PMID- 25768395
TI  - Explaining the variation in lamb longissimus shear force across and within ageing
      periods using protein degradation, sarcomere length and collagen characteristics.
AB  - Meat tenderness is known to be affected by sarcomere length (SL), proteolysis and
      collagen content (CC). Sixty lambs were slaughtered and the Longissimus muscle
      was sampled. Samples for shear force (SF), SL, proteolysis indicators (desmin
      degradation, particle size: PS) and CC were taken after the allotted ageing
      periods (1, 7, and 14 days). PS explained a large part of the variation in shear
      force (approximately 34%) when modelled across ageing periods. Other factors (CC,
      SL) combined with proteolysis indicators (PS, desmin degradation) explained just
      under 40% of the variation in shear force. Within ageing periods SL explained a
      small, but significant, part of the variation in shear force after 14 days of
      ageing (8%) and at day 1 of ageing desmin degradation explained 17% of the
      variation in shear force. Methods to improve the tenderness of lamb longissimus
      muscle should focus on increasing the extent of post-mortem proteolysis, when
      processing conditions are sufficient to prevent muscle fibre shortening.

PMID- 25768396
TI  - Mutations of the human interferon alpha-2b (hIFN-alpha2b) gene in occupationally
      protracted low dose radiation exposed personnel.
AB  - Ionizing radiations impact human tissues by affecting the DNA bases which
      constitute genes. Human interferon alpha 2b gene synthesizes a protein which is
      an important anticancerous, immunomodulatory, anti-proliferative and antiviral
      protein. This study was aimed to identify interferon alpha-2b mutations as a
      consequence of the use of occupational chronic low dose radiation by hospital
      radiation exposed workers. A molecular analysis was done in which DNAs were
      extracted from blood samples from radiology, radiotherapy and nuclear medicine
      workers. The gene was amplified through polymerase chain reaction and further
      genetic data from sequencing results analyzed by bioinformatics tools in order to
      determine as to how mutations in interferon alpha 2b sequences will lead to
      changes in human interferon alpha-2b protein. A total of 41% gene mutations was
      detected among all radiation exposed workers in which higher percentage (5.4%) of
      base insertion mutations and 14% frameshift mutations were found in radiology
      workers. The chronic use of low dose of radiations by occupational workers has a
      significant correlation with mutational effects on interferon alpha 2b gene,
      further evident by depressed interferon alpha levels in serum. This can lead to
      depressed immunity in radiation exposed workers. Hematological profiling of this
      group also showed hyperimmune response in the form of lymphocytosis. 

PMID- 25768397
TI  - Assessing possible DSM-5 ASD subtypes in a sample of victims meeting caseness for
      DSM-5 ASD based on self-report following multiple forms of traumatic exposure.
AB  - Acute stress disorder (ASD) was introduced into the DSM-IV to recognize early
      traumatic responses and as a precursor of PTSD. Although the diagnostic criteria
      for ASD were altered and structured more similarly to the PTSD definition in DSM
      5, only the PTSD diagnosis includes a dissociative subtype. Emerging research has
      indicated that there also appears to be a highly symptomatic subtype for ASD.
      However, the specific nature of the subtype is currently unclear. The present
      study investigates the possible presence of ASD subtypes in a mixed sample of
      victims meeting caseness for DSM-5 ASD based on self-report following four
      different types of traumatic exposure (N=472). The results of latent profile
      analysis revealed a 5-class solution. The highly symptomatic class was marked by
      high endorsement on avoidance and dissociation compared to the other classes.
      Findings are discussed in regard to its clinical implications including the
      implications for the pending the ICD-11 and the recently released DSM-5. 

PMID- 25768398
TI  - Assessing the underlying dimensionality of DSM-5 PTSD symptoms in Chinese
      adolescents surviving the 2008 Wenchuan earthquake.
AB  - By analyzing data yielded from a sample of Chinese adolescents surviving a high
      intensity earthquake, this study investigated the underlying dimensionality of
      DSM-5 PTSD symptoms. The sample included 743 traumatized middle school students
      (396 females and 332 males) aged 11-17 years (mean=13.6, SD=1.0). Results of
      confirmatory factor analysis showed that an intercorrelated seven-factor model
      comprised of intrusion, avoidance, negative affect, anhedonia, externalizing
      behaviors, anxious arousal, and dysphoric arousal factors provided a significant
      better representation of DSM-5 PTSD symptoms than other alternative models.
      Further analyses indicated that external measures of major depression disorder
      and panic disorder symptoms displayed unique associations with four PTSD factors.
      The findings provide further support for the newly proposed seven-factor model of
      DSM-5 PTSD symptoms, add to very limited empirical knowledge on the latent
      structure of DSM-5 PTSD symptoms among adolescents, and carry implications for
      further refinement of the current classifications of PTSD symptoms and further
      clinical practice and research on posttraumatic stress symptomatology. 

PMID- 25768399
TI  - The prevalence of posttraumatic stress disorder in Operation Enduring
      Freedom/Operation Iraqi Freedom (OEF/OIF) Veterans: a meta-analysis.
AB  - Literature on posttraumatic stress disorder (PTSD) prevalence among Operations
      Enduring Freedom and Iraqi Freedom (OEF/OIF) veterans report estimates ranging
      from 1.4% to 60%. A more precise estimate is necessary for projecting healthcare
      needs and informing public policy. This meta-analysis examined 33 studies
      published between 2007 and 2013 involving 4,945,897 OEF/OIF veterans, and PTSD
      prevalence was estimated at 23%. Publication year and percentage of Caucasian
      participants and formerly active duty participants explained significant
      variability in prevalence across studies. PTSD remains a concern for a
      substantial percentage of OEF/OIF veterans. To date, most studies have estimated
      prevalence among OEF/OIF veterans using VA medical chart review. Thus, results
      generalize primarily to the prevalence of PTSD in medical records of OEF/OIF
      veterans who use VA services. Additional research is needed with randomly
      selected, representative samples administered diagnostic interviews. Significant
      financial and mental health resources are needed to promote recovery from PTSD. 

PMID- 25768400
TI  - Dysregulated choline metabolism in T-cell lymphoma: role of choline kinase-alpha
      and therapeutic targeting.
AB  - Cancer cells have distinct metabolomic profile. Metabolic enzymes regulate key
      oncogenic signaling pathways and have an essential role on tumor progression.
      Here, serum metabolomic analysis was performed in 45 patients with T-cell
      lymphoma (TCL) and 50 healthy volunteers. The results showed that dysregulation
      of choline metabolism occurred in TCL and was related to tumor cell
      overexpression of choline kinase-alpha (Chokalpha). In T-lymphoma cells,
      pharmacological and molecular silencing of Chokalpha significantly decreased Ras
      GTP activity, AKT and ERK phosphorylation and MYC oncoprotein expression, leading
      to restoration of choline metabolites and induction of tumor cell
      apoptosis/necropotosis. In a T-lymphoma xenograft murine model, Chokalpha
      inhibitor CK37 remarkably retarded tumor growth, suppressed Ras-AKT/ERK
      signaling, increased lysophosphatidylcholine levels and induced in situ cell
      apoptosis/necropotosis. Collectively, as a regulatory gene of aberrant choline
      metabolism, Chokalpha possessed oncogenic activity and could be a potential
      therapeutic target in TCL, as well as other hematological malignancies with
      interrupted Ras signaling pathways. 

PMID- 25768401
TI  - Evaluation of plitidepsin in patients with primary myelofibrosis and post
      polycythemia vera/essential thrombocythemia myelofibrosis: results of preclinical
      studies and a phase II clinical trial.
AB  - Previous data established that plitidepsin, a cyclic depsipeptide, exerted
      activity in a mouse model of myelofibrosis (MF). New preclinical experiments
      reported herein found that low nanomolar plitidepsin concentrations potently
      inhibited the proliferation of JAK2V617F-mutated cell lines and reduced colony
      formation by CD34+ cells of individuals with MF, at least in part through
      modulation of p27 levels. Cells of MF patients had significantly reduced p27
      content, that were modestly increased upon plitidepsin exposure. On these
      premise, an exploratory phase II trial evaluated plitidepsin 5 mg/m(2) 3-h
      intravenous infusion administered on days 1 and 15 every 4 weeks (q4wk). Response
      rate (RR) according to the International Working Group for Myelofibrosis Research
      and Treatment consensus criteria was 9.1% (95% CI, 0.2-41.3%) in 11 evaluable
      patients during the first trial stage. The single responder achieved a red cell
      transfusion independence and stable disease was reported in nine additional
      patients (81.8%). Eight patients underwent a short-lasting improvement of
      splenomegaly. In conclusion, plitidepsin 5 mg/m(2) 3-h infusion q4wk was well
      tolerated but had a modest activity in patients with primary, post-polycythaemia
      vera or post-essential thrombocythaemia MF. Therefore, this trial was prematurely
      terminated and we concluded that further clinical trials with plitidepsin as
      single agent in MF are not warranted. 

PMID- 25768402
TI  - Transmission of psoriasis by allogeneic bone marrow transplantation and blood
      transfusion.

PMID- 25768403
TI  - Subtotal splenectomy for the treatment of chronic lymphocytic leukemia.

PMID- 25768404
TI  - Human cord blood-derived primitive CD34-negative hematopoietic stem cells (HSCs)
      are myeloid-biased long-term repopulating HSCs.

PMID- 25768406
TI  - Drug response profiling can predict response to ponatinib in a patient with
      t(1;9)(q24;q34)-associated B-cell acute lymphoblastic leukemia.

PMID- 25768405
TI  - The relationship of TP53 R72P polymorphism to disease outcome and TP53 mutation
      in myelodysplastic syndromes.
AB  - Nonsynonymous TP53 exon 4 single-nucleotide polymorphism (SNP), R72P, is linked
      to cancer and mutagen susceptibility. R72P associations with specific cancer
      risk, particularly hematological malignancies, have been conflicting.
      Myelodysplastic syndrome (MDS) with chromosome 5q deletion is characterized by
      erythroid hypoplasia arising from lineage-specific p53 accumulation resulting
      from ribosomal insufficiency. We hypothesized that apoptotically diminished R72P
      C-allele may influence predisposition to del(5q) MDS. Bone marrow and blood DNA
      was sequenced from 705 MDS cases (333 del(5q), 372 non-del(5q)) and 157 controls.
      Genotype distribution did not significantly differ between del(5q) cases (12.6%
      CC, 38.1% CG, 49.2% GG), non-del(5q) cases (9.7% CC, 44.6% CG, 45.7% GG) and
      controls (7.6% CC, 37.6% CG, 54.8% GG) (P=0.13). Allele frequency did not differ
      between non-del(5q) and del(5q) cases (P=0.91) but trended towards increased C
      allele frequency comparing non-del(5q) (P=0.08) and del(5q) (P=0.10) cases with
      controls. Median lenalidomide response duration increased proportionate to C
      allele dosage in del(5q) patients (2.2 (CC), 1.3 (CG) and 0.89 years (GG)).
      Furthermore, C-allele homozygosity in del(5q) was associated with prolonged
      overall and progression-free survival and non-terminal interstitial deletions
      that excluded 5q34, whereas G-allele homozygozity was associated with inferior
      outcome and terminal deletions involving 5q34 (P=0.05). These findings comprise
      the largest MDS R72P SNP analysis.

PMID- 25768407
TI  - Histologically transformed follicular lymphoma exhibits protein profiles
      different from both non-transformed follicular and de novo diffuse large B-cell
      lymphoma.

PMID- 25768408
TI  - Integrating current treatment options for TKI-resistant chronic myeloid leukemia.
AB  - Chronic myeloid leukemia (CML) is a myeloproliferative disorder that accounts for
      approximately 10% of new cases of leukemia. The introduction of tyrosine kinase
      inhibitors (TKIs) has led to a reduction in mortality rates, and the estimated
      prevalence of CML is increasing accordingly. Most patients with CML are diagnosed
      in the chronic phase, and approximately 15% to 30% of these patients will meet
      some definition of resistance to imatinib. In the more advanced phases of
      disease, the rates of imatinib resistance are much higher. Both the National
      Comprehensive Cancer Network (NCCN) and the European LeukemiaNet (ELN) guidelines
      emphasize adequate monitoring of patients to ensure that they are meeting
      treatment milestones. Loss of response is most commonly associated with the
      acquisition of resistance-conferring kinase domain point mutations within BCR
      ABL1. The multiple treatment options available for patients with imatinib
      resistant CML include dasatinib, nilotinib, bosutinib, and ponatinib, as well as
      the non-TKI salvage agent omacetaxine mepesuccinate. Treatment selection is based
      on factors such as the patient's disease state, prior therapies, comorbidities,
      treatment toxicity, and goals of therapy. This clinical roundtable monograph
      provides expert discussion on the monitoring of TKI-resistant CML, when to change
      therapy, and how to select the best treatment option.

PMID- 25768412
TI  - Enhanced biomass and oil production from sugarcane bagasse hydrolysate (SBH) by
      heterotrophic oleaginous microalga Chlorella protothecoides.
AB  - The potential use of sugarcane bagasse hydrolysate (SBH) for microalgal oil in a
      heterotrophic mode and the oil accumulation mechanisms by SBH-induced Chlorella
      protothecoides cells were investigated in this study. Results demonstrated that
      SBH performed better than glucose for cell growth and lipid accumulation under
      the same reducing sugar concentration. The lipid productivity of 0.69g/L/d was
      accomplished at 40g/L of reducing sugar by batch culture. Under the fed-batch
      culture condition, the maximum biomass and lipid productivity were 24.01g/L and
      1.19g/L/d, respectively. Metabolic pathway analysis results indicated that xylose
      and arabinose involved in pentose phosphate pathway might be predominant over
      sole glucose involved in glycolysis for lipid accumulation in cells. Three
      metabolic checkpoints in the proposed metabolic network, including xylulose
      kinase, acyl-CoA dehydrogenase, and dihydrolipoyl dehydrogenase reveal new
      possibilities in developing genetic and metabolic engineering microalgae for
      desirable lipid productivity. 

PMID- 25768413
TI  - Ultrasound-assisted biodiesel production from Camelina sativa oil.
AB  - The main drawbacks of biodiesel production are high reaction temperatures,
      stirring and time. These could be alleviated by aiding transesterification with
      alternative energy sources, i.e. ultrasound (US). In this study, biodiesel was
      obtained from Camelina sativa oil, aided with an ultrasonic probe (20kHz, 70%
      duty cycle, 50% amplitude). Design of experiments included the combination of
      sonication and agitation cycles, w/wo heating (50 degrees C). To gain knowledge
      about the implications of the proposed methodology, conventional
      transesterification was optimized, resulting in higher needs on catalyst
      concentration and reaction time, compared to the proposed reaction. Although FAME
      content met EN 14103 standard, FAME yields were lower than those provided by US
      assisted transesterification. Energy consumption measurements showed that
      ultrasound assisted transesterification required lower energy, temperature,
      catalyst and reaction time. 

PMID- 25768414
TI  - Effects of ZnO nanoparticles on wastewater treatment and their removal behavior
      in a membrane bioreactor.
AB  - Long-term effects of ZnO nanoparticles on the system performance of an MBR were
      investigated together with their removal behavior in the system. Continuous
      operation over 242days showed that ZnO NPs at both 1.0 and 10.0mg/L caused
      moderate deterioration in the removal of COD, nitrogen and phosphorus.
      Denitrification was affected upon the exposure but recovered subsequently.
      Although no significant acute effect on ammonia-oxidization was observed,
      permanent inhibition occurred after long-term exposure. Nitrite-oxidization was
      not affected even with 10.0mg/L ZnO NPs. Significant changes were observed in
      activated sludge properties which resulted in severe membrane fouling. Although
      ZnO NPs caused changes in the bacteria community structure, the diversity however
      remain unchanged. ZnO NPs was removed effectively in the MBR (>98%) with
      biosorption being a major removal mechanism. Membrane filtration also played an
      important role (20% of the total removal) especially at high ZnO NPs
      concentrations (around 10.0mg/L). 

PMID- 25768415
TI  - Partial nitrification in an air-lift reactor with long-term feeding of increasing
      ammonium concentrations.
AB  - The partial nitrification (PN) performance under high ammonium concentrations was
      evaluated in an airlift reactor (ALR). The ALR was operated for 253days with
      stepwise elevation of ammonium concentration to 1400mg/L corresponding nitrogen
      loading rate of 2.1kg/m(3)/d. The ammonium removal rate was finally developed to
      2.0kg/m(3)/d with average removal efficiency above 91% and nitrite accumulation
      percentage of 80%. Results showed that the combined effect of limited DO, high
      bicarbonate, pH and free ammonia (FA) contributed to the stable nitrite
      accumulation substantially. The biomass in the ALR was improved with the
      inception of granulation. Precipitates on biomass surface was unexpectedly
      experienced which might improve the settleability of PN biomass. Organic
      functional groups attached to the PN biomass suggested the possible absorbability
      to different types of pollutant. The results provided important evidence for the
      possibility of applying an ALR to treat high strength ammonium wastewater. 

PMID- 25768416
TI  - Fermentative l-lactic acid production from pretreated whole slurry of oil palm
      trunk treated by hydrothermolysis and subsequent enzymatic hydrolysis.
AB  - A simple and cost-effective biochemical conversion process consisting of
      hydrothermal treatment, enzymatic hydrolysis and fermentation of pretreated whole
      slurry (PWS) was developed for producing l-lactic acid (L-LA) from oil palm trunk
      (OPT). When OPT was hydrothermally treated at optimal condition capable of
      achieving maximum yield of hemicellulosic sugars after enzymatic hydrolysis, the
      enzymatic digestibility of the PWS afforded a yield of 81.4% of the theoretical
      glucose yield (TGY). However, glucose yield from washed pretreated solid (WPS)
      was only 43.5% of TGY. The use of two hydrolysates from PWS and WPS for
      fermentation by Lactobacillus paracasei engineered to selectively produce L-LA
      afforded yields of 89.5% and 45.8% of the theoretical LA yield (TLY),
      respectively. This study confirmed the inevitable extensive sugar loss during
      washing of pretreated slurry due to loss of soluble starch. Alternatively, the
      proposed design process is considered suitable for converting OPT to L-LA without
      such starch loss. 

PMID- 25768417
TI  - Pretreatment of wheat straw with potassium hydroxide for increasing enzymatic and
      microbial degradability.
AB  - The pretreatment of wheat straw with potassium hydroxide (KOH) at ambient
      temperature (20 degrees C) was investigated. The pretreatment effects on chemical
      composition and physical structures, and subsequent enzymatic hydrolysis and
      anaerobic digestion were evaluated. Wheat straw at 10% total solids (TS) was
      treated with KOH solution for 24h at a wide range of KOH loadings from 2% to 50%
      (w/w dry basis). Higher KOH loading resulted in higher lignin reduction from the
      straw and chemical oxygen demand (COD) in the resulting black liquor. Maximum
      lignin reduction of 54.7% was observed at 50% KOH loading. In comparison to
      untreated straw, specific hydrolysis yields achieved 14.0-92.3% over the range of
      2-50% KOH loading, and methane yields increased 16.7-77.5% for KOH loadings of 10
      50%, respectively. Accounting for losses during pretreatment, 20% KOH loading
      resulted in maximum overall reducing sugar yield and methane yield and therefore
      is the recommended loading for pretreatment under these conditions. 

PMID- 25768418
TI  - Effect of pretreatment methods on the synergism of cellulase and xylanase during
      the hydrolysis of bagasse.
AB  - The effect of pretreatment with peracetic acid (PAA) or an ionic liquid (1-ethyl
      3-methylimidazolium acetate, [Emim][OAc]) on the synergism between endoglucanase
      and endoxylanase in the hydrolysis of bagasse was investigated. An endoglucanase,
      Cel6A, with a carbohydrate-binding module (CBM) and two endoxylanases, XynZ-C
      without a CBM and Xyn11A with an intrinsic xylan/cellulose binding module (XBM),
      were selected. The hemicellulose content, especially arabinan, and the cellulose
      crystallinity of bagasse were found to affect the cellulase-xylanase synergism.
      More specifically, higher synergism (above 3.4) was observed for glucan
      conversion, at low levels of arabinan (0.9%), during the hydrolysis of PAA
      pretreated bagasse. In contrast, [Emim][OAc] pretreated bagasse, showed lower
      cellulose crystallinity and achieved higher synergism (over 1.9) for xylan
      conversion. Ultimately, the combination of Cel6A and Xyn11A resulted in higher
      synergism for glucan conversion than the combination of Cel6A with XynZ-C,
      indicating the importance of the molecular architecture of enzymes for metabolic
      synergism. 

PMID- 25768419
TI  - Lignin-based polyoxyethylene ether enhanced enzymatic hydrolysis of
      lignocelluloses by dispersing cellulase aggregates.
AB  - Water-soluble lignin-based polyoxyethylene ether (EHL-PEG), prepared from
      enzymatic hydrolysis lignin (EHL) and polyethylene glycol (PEG1000), was used to
      improve enzymatic hydrolysis efficiency of corn stover. The glucose yield of corn
      stover at 72h was increased from 16.7% to 70.1% by EHL-PEG, while increase in
      yield with PEG4600 alone was 52.3%. With the increase of lignin content, EHL-PEG
      improved enzymatic hydrolysis of microcrystalline cellulose more obvious than
      PEG4600. EHL-PEG could reduce at least 88% of the adsorption of cellulase on the
      lignin film measured by quartz crystal microbalance with dissipation monitoring
      (QCM-D), while reduction with PEG4600 was 43%. Cellulase aggregated at 1220nm in
      acetate buffer analyzed by dynamic light scattering. EHL-PEG dispersed cellulase
      aggregates and formed smaller aggregates with cellulase, thereby, reduced
      significantly nonproductive adsorption of cellulase on lignin and enhanced
      enzymatic hydrolysis of lignocelluloses. 

PMID- 25768420
TI  - Influence of NaOH and thermal pretreatment on dewatered activated sludge
      solubilisation and subsequent anaerobic digestion: Focused on high-solid state.
AB  - In this study, the influence of NaOH and thermal pretreatment of dewatered
      activated sludge (DAS) on the high-solid solubilisation and anaerobic digestion
      was separately investigated by monitoring common parameters. The results
      indicated that COD, proteins and carbohydrates were efficiently solubilised in
      both NaOH and thermal pretreated DAS samples. For NaOH pretreatment, the
      concentrations of volatile fatty acids (VFAs) and total ammonium nitrogen (TAN)
      firstly increased followed by decreasing with NaOH dose increasing. However, they
      decreased with the severity of thermal pretreatment. During the batch digestion
      experiments (at 37 degrees C), for 80mg NaOHg(-1) total solid (TS) DAS
      pretreatment it resulted in a 6.99% decrease in cumulative methane yield (CMY)
      compared to untreated DAS. While for 80, 100, 120 degrees C and 20mg NaOH
      pretreatment, CMY increased by 15%, 42%, 71% and 35%, respectively, in comparison
      to untreated DAS. 

PMID- 25768421
TI  - Using carbon dioxide to maintain an elevated oleaginous microalga concentration
      in mixed-culture photo-bioreactors.
AB  - Microbial contamination of growth reactors is a major concern for microalgal
      biofuel production. In this study, the oleaginous, CO2-tolerant microalga
      Scenedesmus dimorphus was combined with a wastewater-derived microbial community
      and grown in replicated sequencing batch photobioreactors. The reactors were
      sparged with either ambient air or 20% v/v CO2. In the initial growth cycles, air
      and the 20% CO2 reactors were similar in terms of growth and microbial community
      structure. Beyond the fourth growth cycle, however, the ambient air reactors had
      larger decreases in cell density and growth rate, and increases in species
      richness and non-algal microorganisms compared to the 20% CO2 reactors. Both qPCR
      and rDNA sequence analyses demonstrated a greater loss in S. dimorphus enrichment
      in the ambient-air reactors compared to the 20% CO2 reactors. These results
      demonstrate that environmental parameters can be used to delay the adverse
      impacts of microbial contamination in open, mixed-culture microalgae bioreactors.

PMID- 25768422
TI  - Genotypic variation in the uptake, accumulation, and translocation of di-(2
      ethylhexyl) phthalate by twenty cultivars of rice (Oryza sativa L.).
AB  - Agricultural soil in China contains high levels of di-(2-ethylhexyl) phthalate
      (DEHP), especially in paddy-field soil of Guangdong province of China, but the
      accumulation and translocation of DEHP by rice (Oryza sativa L.) remains unknown.
      In the present study, twenty rice cultivars were cultivated in paddy soil spiked
      with DEHP, and variations in DEHP accumulation and translocation among various
      cultivars were investigated. Our results showed that DEHP concentrations in roots
      and shoots of different rice cultivars at four growth stages (i.e., ripening,
      tillering, jointing, and flowering stages) varied greatly from 0.26 to 11.8 mg/kg
      (dry weight, dw) and 0.40 to 7.58 mg/kg (dw), respectively. No obvious change
      over time was observed. The greatest variation in DEHP concentrations among the
      rice cultivars occurred at ripening stage, whereas the lowest variation at
      flowering stage. During ripening stage, the largest variation in DEHP
      concentrations among cultivars were observed in stems (varying from 0.35 to 13.2
      mg/kg), whereas the least one was observed in roots (ranging from 1.01 to 5.72
      mg/kg). Significant differences in DEHP concentrations in the roots, stems,
      leaves and grains of most rice cultivars were found. The translocation factors of
      DEHP from roots to stems or stems to leaves were higher than those from shoots to
      grains. Overall, cultivars Tianfengyou 316, Wuyou 308, and Peizataifeng, which
      contained low levels of DEHP in grains but high levels in shoots, were ideal
      cultivars for simultaneous production of safe food and phytoremediation of
      contaminated soil.

PMID- 25768423
TI  - Effects of microcystin-LR, cylindrospermopsin and a microcystin
      LR/cylindrospermopsin mixture on growth, oxidative stress and mineral content in
      lettuce plants (Lactuca sativa L.).
AB  - Toxic cyanobacterial blooms are documented worldwide as an emerging environmental
      concern. Recent studies support the hypothesis that microcystin-LR (MC-LR) and
      cylindrospermopsin (CYN) produce toxic effects in crop plants. Lettuce (Lactuca
      sativa L.) is an important commercial leafy vegetable that supplies essential
      elements for human nutrition; thus, the study of its sensitivity to MC-LR, CYN
      and a MC-LR/CYN mixture is of major relevance. This study aimed to assess the
      effects of environmentally relevant concentrations (1, 10 and 100 ug/L) of MC-LR,
      CYN and a MC-LR/CYN mixture on growth, antioxidant defense system and mineral
      content in lettuce plants. In almost all treatments, an increase in root fresh
      weight was obtained; however, the fresh weight of leaves was significantly
      decreased in plants exposed to 100 ug/L concentrations of each toxin and the
      toxin mixture. Overall, GST activity was significantly increased in roots,
      contrary to GPx activity, which decreased in roots and leaves. The mineral
      content in lettuce leaves changed due to its exposure to cyanotoxins; in general,
      the mineral content decreased with MC-LR and increased with CYN, and apparently
      these effects are time and concentration-dependent. The effects of the MC-LR/CYN
      mixture were almost always similar to the single cyanotoxins, although MC-LR
      seems to be more toxic than CYN. Our results suggest that lettuce plants in non
      early stages of development are able to cope with lower concentrations of MC-LR,
      CYN and the MC-LR/CYN mixture; however, higher concentrations (100 ug/L) can
      affect both lettuce yield and nutritional quality.

PMID- 25768424
TI  - Neurotoxic effect of triazophos on goldfish (Carassius auratus) and tissue
      specific antioxidant responses.
AB  - Due to the high chemical and photochemical stability, an organophosphorus
      pesticide triazophos might enter aquatic ecosystems and impose negative effect on
      aquatic organisms. In order to investigate short-term toxicity of triazophos on
      goldfish (Carassius auratus), antioxidant response in brain, spleen, kidney and
      liver was tested in this study. As a confirmation, the impact of triazophos on
      acetyl cholinesterase (AChE) activity was found a reduction in all studied
      tissues, especially in brain. In addition, 0.1 and 0.5 mg L(-1) triazophos
      induced MDA level increased, while glutathione content (GSH), superoxide
      dismutase (SOD), catalase (CAT) and lactate dehydrogenase (LDH) activities
      decreased. Of note, more prominent oxidative stress was provoked in kidney and
      liver, but weaker in brain and spleen. These results revealed that triazophos
      could cause a generalized oxidative stress and tissue specific antioxidant
      response in goldfish. Furthermore, neuroendocrine-growth-related gene expression
      (growth hormone (GH), luteinizing hormone (LH) and peptide YY) in brain was also
      changed by exposed to triazophos during 4 and 7d exposure periods. Linked with
      the above results, the present study pointed out that triazophos might induce a
      neurotoxic effect and oxidative damage in goldfish, and the goldfish brain should
      be a critical target for triazophos-induced damage.

PMID- 25768425
TI  - Ventromedial prefrontal cortex stimulation enhances memory and hippocampal
      neurogenesis in the middle-aged rats.
AB  - Memory dysfunction is a key symptom of age-related dementia. Although recent
      studies have suggested positive effects of electrical stimulation for memory
      enhancement, its potential targets remain largely unknown. In this study, we
      hypothesized that spatially targeted deep brain stimulation of ventromedial
      prefrontal cortex enhanced memory functions in a middle-aged rat model. Our
      results show that acute stimulation enhanced the short-, but not the long-term
      memory in the novel-object recognition task. Interestingly, after chronic high
      frequency stimulation, both the short- and long-term memories were robustly
      improved in the novel-object recognition test and Morris water-maze spatial task
      compared to sham. Our results also demonstrated that chronic ventromedial
      prefrontal cortex high-frequency stimulation upregulated neurogenesis-associated
      genes along with enhanced hippocampal cell proliferation. Importantly, these
      memory behaviors were strongly correlated with the hippocampal neurogenesis.
      Overall, these findings suggest that chronic ventromedial prefrontal cortex high
      frequency stimulation may serve as a novel effective therapeutic target for
      dementia-related disorders. 

PMID- 25768427
TI  - Gelation mechanism of tetra-armed poly(ethylene glycol) in aprotic ionic liquid
      containing nonvolatile proton source, protic ionic liquid.
AB  - We report the gelation mechanism of tetra-armed prepolymer chains in typical
      aprotic ionic liquid (aIL), i.e., A-B type cross-end coupling reaction of tetra
      armed poly(ethylene glycol)s with amine and activated ester terminals (TetraPEG
      NH2 and TetraPEG-NHS, respectively) in 1-ethyl-3-methylimidazolium
      bis(trifluoromethanesulfonyl)amide ([C2mIm][TFSA]). In the ion gel system, we
      focused on the pH (or H(+) concentration) dependence of the gelation reaction. We
      thus applied the protic ionic liquid (pIL), 1-ethylimidazolium TFSA
      ([C2ImH][TFSA]), as a nonvolatile H(+) source, and added it into the solvent aIL.
      It was found that the gelation time of TetraPEG ion gel can be successfully
      controlled from 1 min to 3 h depending on the concentration of pIL (cpIL = 0-3
      mM). This suggests that the acid-base properties of TetraPEG-NH2 showing acid
      base equilibrium (-NH2 + H(+) ? -NH3(+)) in the solutions play a key role in the
      gelation process. The acid dissociation constants, pKa's of TetraPEG-NH3(+) and
      C2ImH(+) (cation of pIL) in aIL were directly determined by potentiometric
      titration to be 16.4 and 13.7, respectively. This indicates that most of the H(+)
      ions bind to TetraPEG-NH2 and then C2ImH(+) exists as neutral C2Im. The reaction
      efficiency of amide bond (cross-linked point) systematically decreased with
      increasing cpIL, which was reflected to the mechanical strength of the ion gels.
      From these results, we discuss the gelation mechanism of TetraPEG in aIL to point
      out the relationship between polymer network structure and [H(+)] in the
      solutions. 

PMID- 25768426
TI  - Evolution of alternative biosynthetic pathways for vitamin C following plastid
      acquisition in photosynthetic eukaryotes.
AB  - Ascorbic acid (vitamin C) is an enzyme co-factor in eukaryotes that also plays a
      critical role in protecting photosynthetic eukaryotes against damaging reactive
      oxygen species derived from the chloroplast. Many animal lineages, including
      primates, have become ascorbate auxotrophs due to the loss of the terminal enzyme
      in their biosynthetic pathway, L-gulonolactone oxidase (GULO). The alternative
      pathways found in land plants and Euglena use a different terminal enzyme, L
      galactonolactone dehydrogenase (GLDH). The evolutionary processes leading to
      these differing pathways and their contribution to the cellular roles of
      ascorbate remain unclear. Here we present molecular and biochemical evidence
      demonstrating that GULO was functionally replaced with GLDH in photosynthetic
      eukaryote lineages following plastid acquisition. GULO has therefore been lost
      repeatedly throughout eukaryote evolution. The formation of the alternative
      biosynthetic pathways in photosynthetic eukaryotes uncoupled ascorbate synthesis
      from hydrogen peroxide production and likely contributed to the rise of ascorbate
      as a major photoprotective antioxidant.

PMID- 25768428
TI  - Effect of lipid headgroup charge and pH on the stability and membrane insertion
      potential of calcium condensed gene complexes.
AB  - Noncovalently condensed complexes of genetic material, cell penetrating peptides
      (CPPs), and calcium chloride present a nonviral route to improve transfection
      efficiency of nucleic acids (e.g., pDNA and siRNA). However, the exact mechanisms
      of membrane insertion and delivery of macromolecule complexes to intracellular
      locations as well as their stability in the intracellular environment are not
      understood. We show that calcium condensed gene complexes containing different
      hydrophilic (i.e., dTAT, K9, R9, and RH9) and amphiphilic (i.e., RA9, RL9, and
      RW9) CPPs formed stable cationic complexes of hydrodynamic radii 100 nm at
      neutral pH. However, increasing the acidity caused the complexes to become
      neutral or anionic and increase in size. Using zwitterionic and anionic
      phospholipid monolayers as models that mimic the membrane composition of the
      outer leaflet of cell membranes and intracellular vesicles and pHs that mimic the
      intracellular environment, we study the membrane insertion potential of these
      seven gene complexes (CPP/pDNA/Ca(2+) complexes) into model membranes. At neutral
      pH, all gene complexes demonstrated the highest insertion potential into anionic
      phospholipid membranes, with complexes containing amphiphilic peptides showing
      the maximum insertion. However, at acidic pH, the gene complexes demonstrated
      maximum monolayer insertion into zwitterionic lipids, irrespective of the
      chemical composition of the CPP in the complexes. Our results suggest that in the
      neutral environment the complexes are unable to penetrate the zwitterionic lipid
      membranes but can penetrate through the anionic lipid membranes. However, the
      acidic pH mimicking the local environment in the late endosomes leads to a
      significant increase in adsorption of the complexes to zwitterionic lipid
      headgroups and decreases for anionic headgroups. These membrane-gene complex
      interactions may be responsible for the ability of the complexes to efficiently
      enter the intracellular environment through endocytosis and escape from the
      endosomes to effectively deliver their genetic payload. 

PMID- 25768429
TI  - Sorption and release of organics by primary, anaerobic, and aerobic activated
      sludge mixed with raw municipal wastewater.
AB  - New activated sludge processes that utilize sorption as a major mechanism for
      organics removal are being developed to maximize energy recovery from wastewater
      organics, or as enhanced primary treatment technologies. To model and optimize
      sorption-based activated sludge processes, further knowledge about sorption of
      organics onto sludge is needed. This study compared primary-, anaerobic-, and
      aerobic activated sludge as sorbents, determined sorption capacity and kinetics,
      and investigated some characteristics of the organics being sorbed. Batch
      sorption assays were carried out without aeration at a mixing velocity of 200
      rpm. Only aerobic activated sludge showed net sorption of organics. Sorption of
      dissolved organics occurred by a near-instantaneous sorption event followed by a
      slower process that obeyed 1st order kinetics. Sorption of particulates also
      followed 1st order kinetics but there was no instantaneous sorption event;
      instead there was a release of particles upon mixing. The 5-min sorption capacity
      of activated sludge was 6.5+/-10.8 mg total organic carbon (TOC) per g volatile
      suspend solids (VSS) for particulate organics and 5.0+/-4.7 mgTOC/gVSS for
      dissolved organics. The observed instantaneous sorption appeared to be mainly due
      to organics larger than 20 kDa in size being sorbed, although molecules with a
      size of about 200 Da with strong UV absorbance at 215-230 nm were also rapidly
      removed. 

PMID- 25768430
TI  - Quantification of mature microRNAs using pincer probes and real-time PCR
      amplification.
AB  - The robust and reliable detection of small microRNAs (miRNAs) is important to
      understand the functional significance of miRNAs. Several methods can be used to
      quantify miRNAs. Selectively quantifying mature miRNAs among miRNA precursors,
      pri-miRNAs, and other miRNA-like sequences is challenging because of the short
      length of miRNAs. In this study, we developed a two-step miRNA quantification
      system based on pincer probe capture and real-time PCR amplification. The
      performance of the method was tested using synthetic mature miRNAs and clinical
      RNA samples. Results showed that the method demonstrated dynamic range of seven
      orders of magnitude and sensitivity of detection of hundreds of copies of miRNA
      molecules. The use of pincer probes allowed excellent discrimination of mature
      miRNAs from their precursors with five Cq (quantification cycle) values
      difference. The developed method also showed good discrimination of highly
      homologous family members with cross reaction less than 5%. The pincer probe
      based approach is a potential alternative to currently used methods for mature
      miRNA quantification. 

PMID- 25768431
TI  - Mesoporous silica-layered biopolymer hybrid nanofibrous scaffold: a novel
      nanobiomatrix platform for therapeutics delivery and bone regeneration.
AB  - Nanoscale scaffolds that characterize high bioactivity and the ability to deliver
      biomolecules provide a 3D microenvironment that controls and stimulates desired
      cellular responses and subsequent tissue reaction. Herein novel nanofibrous
      hybrid scaffolds of polycaprolactone shelled with mesoporous silica (PCL@MS) were
      developed. In this hybrid system, the silica shell provides an active
      biointerface, while the 3D nanoscale fibrous structure provides cell-stimulating
      matrix cues suitable for bone regeneration. The electrospun PCL nanofibers were
      coated with MS at controlled thicknesses via a sol-gel approach. The MS shell
      improved surface wettability and ionic reactions, involving substantial formation
      of bone-like mineral apatite in body-simulated medium. The MS-layered hybrid
      nanofibers showed a significant improvement in mechanical properties, in terms of
      both tensile strength and elastic modulus, as well as in nanomechanical surface
      behavior, which is favorable for hard tissue repair. Attachment, growth, and
      proliferation of rat mesenchymal stem cells were significantly improved on the
      hybrid scaffolds, and their osteogenic differentiation and subsequent
      mineralization were highly up-regulated by the hybrid scaffolds. Furthermore, the
      mesoporous surface of the hybrid scaffolds enabled the loading of a series of
      bioactive molecules, including small drugs and proteins at high levels. The
      release of these molecules was sustainable over a long-term period, indicating
      the capability of the hybrid scaffolds to deliver therapeutic molecules. Taken
      together, the multifunctional hybrid nanofibrous scaffolds are considered to be
      promising therapeutic platforms for stimulating stem cells and for the repair and
      regeneration of bone. 

PMID- 25768432
TI  - The diterpenoid 7-keto-sempervirol, derived from Lycium chinense, displays
      anthelmintic activity against both Schistosoma mansoni and Fasciola hepatica.
AB  - BACKGROUND: Two platyhelminths of biomedical and commercial significance are
      Schistosoma mansoni (blood fluke) and Fasciola hepatica (liver fluke). These
      related trematodes are responsible for the chronic neglected tropical diseases
      schistosomiasis and fascioliasis, respectively. As no vaccine is currently
      available for anti-flukicidal immunoprophylaxis, current treatment is mediated by
      mono-chemical chemotherapy in the form of mass drug administration (MDA)
      (praziquantel for schistosomiasis) or drenching (triclabendazole for
      fascioliasis) programmes. This overreliance on single chemotherapeutic classes
      has dramatically limited the number of novel chemical entities entering
      anthelmintic drug discovery pipelines, raising significant concerns for the
      future of sustainable blood and liver fluke control. METHODOLOGY/ PRINCIPLE
      FINDINGS: Here we demonstrate that 7-keto-sempervirol, a diterpenoid isolated
      from Lycium chinense, has dual anthelmintic activity against related S. mansoni
      and F. hepatica trematodes. Using a microtiter plate-based helminth fluorescent
      bioassay (HFB), this activity is specific (Therapeutic index = 4.2, when compared
      to HepG2 cell lines) and moderately potent (LD50 = 19.1 MUM) against S. mansoni
      schistosomula cultured in vitro. This anti-schistosomula effect translates into
      activity against both adult male and female schistosomes cultured in vitro where
      7-keto-sempervirol negatively affects motility/behaviour, surface architecture
      (inducing tegumental holes, tubercle swelling and spine loss/shortening),
      oviposition rates and egg morphology. As assessed by the HFB and microscopic
      phenotypic scoring matrices, 7-keto-sempervirol also effectively kills in vitro
      cultured F. hepatica newly excysted juveniles (NEJs, LD50 = 17.7 MUM). Scanning
      electron microscopy (SEM) evaluation of adult F. hepatica liver flukes co
      cultured in vitro with 7-keto-sempervirol additionally demonstrates phenotypic
      abnormalities including breaches in tegumental integrity and spine loss.
      CONCLUSIONS/ SIGNIFICANCE: 7-keto-sempervirol negatively affects the viability
      and phenotype of two related pathogenic trematodes responsible for significant
      human and animal infectious diseases. This plant-derived, natural product is also
      active against both larval and adult developmental forms. As such, the data
      collectively indicate that 7-keto-sempervirol is an important starting point for
      anthelmintic drug development. Medicinal chemistry optimisation of more potent 7
      keto-sempervirol analogues could lead to the identification of novel chemical
      entities useful for future combinatorial or replacement anthelmintic control.

PMID- 25768433
TI  - Dopaminergic modulation of the voltage-gated sodium current in the cochlear
      afferent neurons of the rat.
AB  - The cochlear inner hair cells synapse onto type I afferent terminal dendrites,
      constituting the main afferent pathway for auditory information flow. This
      pathway receives central control input from the lateral olivocochlear efferent
      neurons that release various neurotransmitters, among which dopamine (DA) plays a
      salient role. DA receptors activation exert a protective role in the over
      activation of the afferent glutamatergic synapses, which occurs when an animal is
      exposed to intense sound stimuli or during hypoxic events. However, the mechanism
      of action of DA at the cellular level is still not completely understood. In this
      work, we studied the actions of DA and its receptor agonists and antagonists on
      the voltage-gated sodium current (INa) in isolated cochlear afferent neurons of
      the rat to define the mechanisms of dopaminergic control of the afferent input in
      the cochlear pathway. Experiments were performed using the voltage and current
      clamp techniques in the whole-cell configuration in primary cultures of cochlear
      spiral ganglion neurons (SGNs). Recordings of the INa showed that DA receptor
      activation induced a significant inhibition of the peak current amplitude,
      leading to a significant decrease in cell excitability. Inhibition of the INa was
      produced by a phosphorylation of the sodium channels as shown by the use of
      phosphatase inhibitor that produced an inhibition analogous to that caused by DA
      receptor activation. Use of specific agonists and antagonists showed that
      inhibitory action of DA was mediated both by activation of D1- and D2-like DA
      receptors. The action of the D1- and D2-like receptors was shown to be mediated
      by a Galphas/AC/cAMP/PKA and Galphaq/PLC/PKC pathways respectively. These results
      showed that DA receptor activation constitutes a significant modulatory input to
      SGNs, effectively modulating their excitability and information flow in the
      auditory pathway. 

PMID- 25768434
TI  - Design and implementation of website information disclosure assessment system.
AB  - Internet application technologies, such as cloud computing and cloud storage,
      have increasingly changed people's lives. Websites contain vast amounts of
      personal privacy information. In order to protect this information, network
      security technologies, such as database protection and data encryption, attract
      many researchers. The most serious problems concerning web vulnerability are e
      mail address and network database leakages. These leakages have many causes. For
      example, malicious users can steal database contents, taking advantage of
      mistakes made by programmers and administrators. In order to mitigate this type
      of abuse, a website information disclosure assessment system is proposed in this
      study. This system utilizes a series of technologies, such as web crawler
      algorithms, SQL injection attack detection, and web vulnerability mining, to
      assess a website's information disclosure. Thirty websites, randomly sampled from
      the top 50 world colleges, were used to collect leakage information. This testing
      showed the importance of increasing the security and privacy of website
      information for academic websites. 

PMID- 25768436
TI  - Generation and regioselective trapping of a 3,4-piperidyne for the synthesis of
      functionalized heterocycles.
AB  - We report the generation of the first 3,4-piperidyne and its use as a building
      block for the synthesis of annulated piperidines. Experimental and computational
      studies of this intermediate are disclosed, along with comparisons to the well
      known 3,4-pyridyne. The distortion/interaction model is used to explain the
      observed regioselectivities. 

PMID- 25768437
TI  - Feeding ecology informs parasite epidemiology: prey selection modulates encounter
      rate with Echinococcus multilocularis in urban coyotes.
AB  - We investigated the role of urban coyote feeding ecology in the transmission of
      Echinococcus multilocularis, the causative agent of Alveolar Echinococcosis in
      humans. As coyotes can play a main role in the maintenance of this zoonotic
      parasite within North American urban settings, such study can ultimately aid
      disease risk management. Between June 2012 and June 2013, we collected 251 coyote
      feces and conducted trapping of small mammals (n = 971) in five parks in the city
      of Calgary, Alberta, Canada. We investigated E. multilocularis epidemiology by
      assessing seasonal variations of coyote diet and the selective consumption of
      different rodent intermediate host species. Furthermore, accounting for small
      mammal digestibility and coyote defecation rates we estimated the number of small
      mammal preys ingested by coyote and consequently, coyote encounter rates with the
      parasite. Dominant food items included small mammals, fruit and vegetation,
      although hare and deer were seasonally relevant. The lowest frequency of
      occurrence per scat of small mammals was recorded in winter (39.4%), when
      consumption of deer was highest (36.4%). However, highest encounter rates (number
      of infected hosts predated/season) with E. multilocularis (95% CI: 1.0-22.4),
      combined with the lack of predation on non-competent small mammal species,
      suggest that winter is the critical season for transmission and control of this
      parasite. Within the small mammal assemblage, voles (Microtus pennsylvanicus and
      Myodes gapperi) were the selected preys of urban coyotes and likely played a key
      role for the maintenance of the urban sylvatic life-cycle of E. multilocularis in
      Calgary.

PMID- 25768435
TI  - Recommendations for a core outcome set for measuring standing balance in adult
      populations: a consensus-based approach.
AB  - BACKGROUND: Standing balance is imperative for mobility and avoiding falls. Use
      of an excessive number of standing balance measures has limited the synthesis of
      balance intervention data and hampered consistent clinical practice. OBJECTIVE:
      To develop recommendations for a core outcome set (COS) of standing balance
      measures for research and practice among adults. METHODOLOGY: A combination of
      scoping reviews, literature appraisal, anonymous voting and face-to-face meetings
      with fourteen invited experts from a range of disciplines with international
      recognition in balance measurement and falls prevention. Consensus was sought
      over three rounds using pre-established criteria. DATA SOURCES: The scoping
      review identified 56 existing standing balance measures validated in adult
      populations with evidence of use in the past five years, and these were
      considered for inclusion in the COS. RESULTS: Fifteen measures were excluded
      after the first round of scoring and a further 36 after round two. Five measures
      were considered in round three. Two measures reached consensus for
      recommendation, and the expert panel recommended that at a minimum, either the
      Berg Balance Scale or Mini Balance Evaluation Systems Test be used when measuring
      standing balance in adult populations. LIMITATIONS: Inclusion of two measures in
      the COS may increase the feasibility of potential uptake, but poses challenges
      for data synthesis. Adoption of the standing balance COS does not constitute a
      comprehensive balance assessment for any population, and users should include
      additional validated measures as appropriate. CONCLUSIONS: The absence of a gold
      standard for measuring standing balance has contributed to the proliferation of
      outcome measures. These recommendations represent an important first step towards
      greater standardization in the assessment and measurement of this critical skill
      and will inform clinical research and practice internationally.

PMID- 25768438
TI  - Meta-analysis of studies using suppression subtractive hybridization and
      microarrays to investigate the effects of environmental stress on gene
      transcription in oysters.
AB  - Many microarray and suppression subtractive hybridization (SSH) studies have
      analyzed the effects of environmental stress on gene transcription in marine
      species. However, there have been no unifying analyses of these data to identify
      common stress response pathways. To address this shortfall, we conducted a meta
      analysis of 14 studies that investigated the effects of different environmental
      stressors on gene expression in oysters. The stressors tested included chemical
      contamination, hypoxia and infection, as well as extremes of temperature, pH and
      turbidity. We found that the expression of over 400 genes in a range of oyster
      species changed significantly after exposure to environmental stress. A repeating
      pattern was evident in these transcriptional responses, regardless of the type of
      stress applied. Many of the genes that responded to environmental stress encoded
      proteins involved in translation and protein processing (including molecular
      chaperones), the mitochondrial electron transport chain, anti-oxidant activity
      and the cytoskeleton. In light of these findings, we put forward a consensus
      model of sub-cellular stress responses in oysters. 

PMID- 25768439
TI  - Phase II study of Pseudomonas aeruginosa-Mannose-Sensitive hemagglutinin in
      combination with capecitabine for Her-2-negative metastatic breast cancer
      pretreated with anthracycline and taxane.
AB  - PURPOSE: Metastatic breast cancer (MBC) remains an incurable disease despite
      major therapeutic advances. Pseudomonas aeruginosa-mannose-sensitive
      hemagglutinin (PA-MSHA) has been established to have anti-proliferative effects
      against breast cancer cells in preclinical experiments, and is indicated for
      treatment of cancer in China. We performed a phase II trial combining PA-MSHA
      with capecitabine in patients with heavily pretreated MBC. METHODS: Eligibility
      criteria included human epidermal growth factor receptor 2-negative MBC, prior
      therapy with anthracyclines and taxanes, at least one prior chemotherapy regimen
      for metastatic disease or early relapse after a taxane plus anthracycline
      adjuvant regimen, and adequate organ function and performance status. PA-MSHA 1
      mg was administered subcutaneously every other day and capecitabine 1000 mg/m2
      orally twice a day for 2 weeks on, 1 week off. The primary end point was
      progression-free survival. RESULTS: A total of 97 patients were enrolled. Median
      progression-free survival (PFS) was 4.0 months [95 % confidence interval (CI) 3.0
      4.9], which was not significantly different from that in historical controls.
      However, median PFS was significantly longer (8.2 months; 95 % CI 6.7-9.7) in 24
      patients with moderate immune-related adverse events (irAEs) such as fever or
      skin induration at the injection site than in those with no or mild irAEs (3.1
      months, 95 % CI 2.5-3.6; p = 0.003). Overall survival was also improved in these
      patients (25.4 vs. 16.4 months; p = 0.044). PA-MSHA has a good safety profile,
      with only 6 patients (6.2 %) discontinuing treatment. PA-MSHA did not increase
      capecitabine-related toxicities such as hand-foot syndrome, nausea, and vomiting.
      CONCLUSION: Adding PA-MSHA to capecitabine has a good safety profile in patients
      with heavily pre-treated MBC, although benefit from this regimen might occur only
      in patients with moderate PA-MSHA-related adverse events. TRIAL REGISTRATION:
      ClinicalTrials.gov NCT01380808.

PMID- 25768440
TI  - Predictive parameters of arteriovenous fistula functional maturation in a
      population of patients with end-stage renal disease.
AB  - INTRODUCTION: With increasing numbers of patients diagnosed with ESRD,
      arteriovenous fistula (AVF) maturation has become a major factor in improving
      both dialysis related outcomes and quality of life of those patients. Compared to
      other types of access it has been established that a functional AVF access is the
      least likely to be associated with thrombosis, infection, hospital admissions,
      secondary interventions to maintain patency and death. AIM: Study of demographic
      factors implicated in the functional maturation of arteriovenous fistulas. Also,
      to explore any possible association between preoperative haematological
      investigations and functional maturation. METHODS: We performed a retrospective
      chart review of all patients with ESRD who were referred to the vascular service
      in the University Hospital of Limerick for creation of vascular access for HD. We
      included patients with primary AVFs; and excluded those who underwent secondary
      procedures. RESULTS: Overall AVF functional maturation rate in our study was
      53.7% (52/97). Female gender showed significant association with nonmaturation (P
      = 0.004) and was the only predictor for non-maturation in a logistic regression
      model (P = 0.011). Patients who had history of renal transplant (P = 0.036), had
      relatively lower haemoglobin levels (P = 0.01) and were on calcium channel
      blockers (P = 0.001) showed better functional maturation rates. CONCLUSION:
      Female gender was found to be associated with functional non-maturation, while a
      history kidney transplant, calcium channel-blocker agents and low haemoglobin
      levels were all associated with successful functional maturation. In view of the
      conflicting evidence in the literature, large prospective multi-centre registry
      based studies with well-defined outcomes are needed.

PMID- 25768441
TI  - Survival of proper hepatic artery lymph node metastasis in patients with gastric
      cancer: implications for D2 lymphadenectomy.
AB  - BACKGROUND AND AIMS: There is a discrepancy between the American Joint Committee
      on Cancer (AJCC) guidelines (7th edition) and the Japanese treatment guidelines
      (3rd edition) with regard to the extent of D2 lymphadenectomy for gastric cancer.
      In the AJCC, hepatic artery station (No.12a) lymph node (LN) metastasis is
      classified as distant metastasis, whereas in the Japanese guidelines, this
      classified is regional metastasis. This study aimed to evaluate whether it is
      appropriate to reclassify No.12a LN metastasis as distant metastasis in
      consideration of survival outcome. METHODS: In this retrospective analysis, data
      from patients with gastric cancer who underwent regular D2 or greater
      lymphadenectomy between 1996 and 2006 were evaluated to determine any association
      between the clinicopathological features of hepatic artery LNs and survival
      prognosis. RESULTS: Among the 247 patients with gastric cancer who underwent
      No.12 LN harvest, 45 (18.2%) were positive for No.12a LN metastasis. No.12a LN
      metastasis was significantly associated with poor clinicopathological features,
      advanced tumor stage, and poor overall survival. The 5-year survival rate of
      patients with No.12a LN metastasis was significantly better than that of patients
      with distant metastasis (P < 0.05), but was similar to that of patients with LN
      involvement in the D2 lymphadenectomy region (P > 0.05). No.12a LN metastasis was
      shown to significantly influence survival outcome in univariate analysis, but was
      not identified as a significant independent predictor in multivariate analysis.
      In logistic multivariate regression analysis, T stage, N stage, and station No.3,
      5, and 6 LN metastasis were independent predictors of No.12a LN involvement.
      CONCLUSIONS: It is inappropriate to reclassify No.12a LN metastasis as distant
      metastasis. We propose that this be considered as regional metastasis and be
      included in the extent of D2 lymphadenectomy to improve survival outcomes in
      patients with gastric cancer.

PMID- 25768443
TI  - Linear thermal circulator based on Coriolis forces.
AB  - We show that the presence of a Coriolis force in a rotating linear lattice
      imposes a nonreciprocal propagation of the phononic heat carriers. Using this
      effect we propose the concept of Coriolis linear thermal circulator which can
      control the circulation of a heat current. A simple model of three coupled
      harmonic masses on a rotating platform permits us to demonstrate giant
      circulating rectification effects for moderate values of the angular velocities
      of the platform. 

PMID- 25768444
TI  - Evidence of a one-step replica symmetry breaking in a three-dimensional Potts
      glass model.
AB  - We study a seven-state Potts glass model in three dimensions with first-, second
      , and third-nearest-neighbor interactions with a bimodal distribution of
      couplings by Monte Carlo simulations. Our results show the existence of a spin
      glass transition at a finite temperature T(c), a discontinuous jump of an order
      parameter at T(c) without latent heat, and a nontrivial structure in the order
      parameter distribution below T(c). They are compatible with one-step replica
      symmetry breaking.

PMID- 25768442
TI  - Activity prediction and molecular mechanism of bovine blood derived angiotensin I
      converting enzyme inhibitory peptides.
AB  - Development of angiotensin I-converting enzyme (ACE, EC 3.4.15.1) inhibitory
      peptides from food protein is under extensive research as alternative for the
      prevention of hypertension. However, it is difficult to identify peptides
      released from food sources. To accelerate the progress of peptide identification,
      a three layer back propagation neural network model was established to predict
      the ACE-inhibitory activity of pentapeptides derived from bovine hemoglobin by
      simulated enzyme digestion. The pentapeptide WTQRF has the best predicted value
      with experimental IC50 23.93 MUM. The potential molecular mechanism of the WTQRF
      / ACE interaction was investigated by flexible docking. 

PMID- 25768445
TI  - Shear-accelerated crystallization in a supercooled atomic liquid.
AB  - A bulk metallic glass forming alloy is subjected to shear flow in its supercooled
      state by compression of a short rod to produce a flat disk. The resulting
      material exhibits enhanced crystallization kinetics during isothermal annealing
      as reflected in the decrease of the crystallization time relative to the
      nondeformed case. The transition from quiescent to shear-accelerated
      crystallization is linked to strain accumulated during shear flow above a
      critical shear rate gamma(c)~0.3 s(-1) which corresponds to Peclet number,
      Pe~O(1). The observation of shear-accelerated crystallization in an atomic system
      at modest shear rates is uncommon. It is made possible here by the substantial
      viscosity of the supercooled liquid which increases strongly with temperature in
      the approach to the glass transition. We may therefore anticipate the encounter
      of nontrivial shear-related effects during thermoplastic deformation of similar
      systems.

PMID- 25768446
TI  - Tuning surface wettability by designing hairy structures.
AB  - We present a molecular dynamics simulation study on the controlling factors that
      influence the wettability of a hairy surface. By adopting the hairs with
      appropriate grafting density, hair length, and hair rigidity, the hairy surface
      shows good performance on droplet repellency. When the droplet sits on the hairy
      surface, the flexible hairs can spontaneously bundle with the appropriate amount
      of neighboring hairs to enhance the surface hydrophobicity, thus providing a new
      possibility to control the surface wettability. The hairy surface with tunable
      grafting density and hair rigidity, bridges the gap between surfaces with soft
      polymer brushes and surfaces that are completely hard but porous. 

PMID- 25768447
TI  - Gene regulation and noise reduction by coupling of stochastic processes.
AB  - Here we characterize the low-noise regime of a stochastic model for a negative
      self-regulating binary gene. The model has two stochastic variables, the protein
      number and the state of the gene. Each state of the gene behaves as a protein
      source governed by a Poisson process. The coupling between the two gene states
      depends on protein number. This fact has a very important implication: There
      exist protein production regimes characterized by sub-Poissonian noise because of
      negative covariance between the two stochastic variables of the model. Hence the
      protein numbers obey a probability distribution that has a peak that is sharper
      than those of the two coupled Poisson processes that are combined to produce it.
      Biochemically, the noise reduction in protein number occurs when the switching of
      the genetic state is more rapid than protein synthesis or degradation. We
      consider the chemical reaction rates necessary for Poisson and sub-Poisson
      processes in prokaryotes and eucaryotes. Our results suggest that the coupling of
      multiple stochastic processes in a negative covariance regime might be a
      widespread mechanism for noise reduction. 

PMID- 25768448
TI  - Reservoir computing with a single time-delay autonomous Boolean node.
AB  - We demonstrate reservoir computing with a physical system using a single
      autonomous Boolean logic element with time-delay feedback. The system generates a
      chaotic transient with a window of consistency lasting between 30 and 300 ns,
      which we show is sufficient for reservoir computing. We then characterize the
      dependence of computational performance on system parameters to find the best
      operating point of the reservoir. When the best parameters are chosen, the
      reservoir is able to classify short input patterns with performance that
      decreases over time. In particular, we show that four distinct input patterns can
      be classified for 70 ns, even though the inputs are only provided to the
      reservoir for 7.5 ns. 

PMID- 25768449
TI  - Noisy localized structures induced by large noise.
AB  - We investigate the influence of large noise on the formation of localized
      patterns in the framework of the cubic-quintic complex Ginzburg-Landau equation.
      The interaction of localization and noise can lead to filling in or noisy
      localized structures for fixed noise strength. To focus on the interaction
      between noise and localization we cover a region in parameter space, in
      particular, subcriticality, for which stationary stable deterministic pulses do
      not exist. Possible experimental tests of the work presented for autocatalytic
      chemical reactions and bioinspired systems are outlined. 

PMID- 25768450
TI  - Pair dispersion of turbulent premixed flame elements.
AB  - Flame particles are mathematical points comoving with a reacting isoscalar
      surface in a premixed flame. In this Rapid Communication, we investigate mean
      square pair separation of flame particles as a function of time from their
      positions tracked in two sets of direct numerical simulation solutions of H(2)
      air turbulent premixed flames with detailed chemistry. We find that, despite
      flame particles and fluid particles being very different concepts, a modified
      Batchelor's scaling of the form <|Delta(F)(t)
      Delta(F)(0)|(2)>=C(F)(<E>(0)(F)Delta(0)(F))(2/3)t(2) holds for flame particle
      pair dispersion. The proportionality constant, however, is not universal and
      depends on the isosurface temperature value on which the flame particles reside.
      Following this, we attempt to analytically investigate the rationale behind such
      an observation.

PMID- 25768451
TI  - High-density carbon capsule experiments on the national ignition facility.
AB  - Indirect-drive implosions with a high-density carbon (HDC) capsule were conducted
      on the National Ignition Facility (NIF) to test HDC properties as an ablator
      material for inertial confinement fusion. A series of five experiments were
      completed with 76-MUm-thick HDC capsules using a four-shock laser pulse optimized
      for HDC. The pulse delivered a total energy of 1.3 MJ with a peak power of 360
      TW. The experiment demonstrated good laser to target coupling (~90%) and
      excellent nuclear performance. A deuterium and tritium gas-filled HDC capsule
      implosion produced a neutron yield of 1.6*10^{15}+/-3*10(13), a yield over
      simulated in one dimension of 70%.

PMID- 25768452
TI  - Rectified motion in an asymmetric channel: the role of hydrodynamic interactions
      with walls.
AB  - Dynamics of a Brownian particle in an asymmetric microchannel that is subjected
      to an external oscillating force is numerically analyzed. In addition to the
      elastic collisions with the walls that are kind of short range interactions, the
      long range hydrodynamic influences of the walls have been considered in an
      approximate way. We demonstrate how the geometrical parameters of the channel
      change the rectified current of the particle. As a result of numerical
      calculations, we show that long range hydrodynamic interactions with walls
      decrease the efficiency of the Brownian ratchet. 

PMID- 25768453
TI  - Random walk model of subdiffusion in a system with a thin membrane.
AB  - We consider in this paper subdiffusion in a system with a thin membrane. The
      subdiffusion parameters are the same in both parts of the system separated by the
      membrane. Using the random walk model with discrete time and space variables the
      probabilities (Green's functions) P(x,t) describing a particle's random walk are
      found. The membrane, which can be asymmetrical, is characterized by the two
      probabilities of stopping a random walker by the membrane when it tries to pass
      through the membrane in both opposite directions. Green's functions are
      transformed to the system in which the variables are continuous, and then the
      membrane permeability coefficients are given by special formulas which involve
      the probabilities mentioned above. From the obtained Green's functions, we derive
      boundary conditions at the membrane. One of the conditions demands the continuity
      of a flux at the membrane, but the other one is rather unexpected and contains
      the Riemann-Liouville fractional time derivative P(x(N)(
      ),t)=lambda(1)P(x(N)(+),t)+lambda(2)?(alpha/2)P(x(N)(+),t)/?t(alpha/2), where
      lambda(1),lambda(2) depending on membrane permeability coefficients (lambda(1)=1
      for a symmetrical membrane), alpha is a subdiffusion parameter, and x(N) is the
      position of the membrane. This boundary condition shows that the additional
      "memory effect," represented by the fractional derivative, is created by the
      membrane. This effect is also created by the membrane for a normal diffusion case
      in which alpha=1.

PMID- 25768454
TI  - Active matter beyond mean-field: ring-kinetic theory for self-propelled
      particles.
AB  - Recently, Hanke et al. [Phys. Rev. E 88, 052309 (2013)] showed that mean-field
      kinetic theory fails to describe collective motion in soft active colloids and
      that correlations must not be neglected. Correlation effects are also expected to
      be essential in systems of biofilaments driven by molecular motors and in swarms
      of midges. To obtain correlations in an active matter system from first
      principles, we derive a ring-kinetic theory for Vicsek-style models of self
      propelled agents from the exact N-particle evolution equation in phase space. The
      theory goes beyond mean-field and does not rely on Boltzmann's approximation of
      molecular chaos. It can handle precollisional correlations and cluster formation,
      which are both important to understand the phase transition to collective motion.
      We propose a diagrammatic technique to perform a small-density expansion of the
      collision operator and derive the first two equations of the Bogoliubov-Born
      Green-Kirkwood-Yvon (BBGKY) hierarchy. An algorithm is presented that numerically
      solves the evolution equation for the two-particle correlations on a lattice.
      Agent-based simulations are performed and informative quantities such as
      orientational and density correlation functions are compared with those obtained
      by ring-kinetic theory. Excellent quantitative agreement between simulations and
      theory is found at not-too-small noises and mean free paths. This shows that
      there are parameter ranges in Vicsek-like models where the correlated closure of
      the BBGKY hierarchy gives correct and nontrivial results. We calculate the
      dependence of the orientational correlations on distance in the disordered phase
      and find that it seems to be consistent with a power law with an exponent around 
      1.8, followed by an exponential decay. General limitations of the kinetic theory
      and its numerical solution are discussed.

PMID- 25768455
TI  - Families of Fokker-Planck equations and the associated entropic form for a
      distinct steady-state probability distribution with a known external force field.
AB  - A method of finding entropic form for a given stationary probability distribution
      and specified potential field is discussed, using the steady-state Fokker-Planck
      equation. As examples, starting with the Boltzmann and Tsallis distribution and
      knowing the force field, we obtain the Boltzmann-Gibbs and Tsallis entropies.
      Also, the associated entropy for the gamma probability distribution is found,
      which seems to be in the form of the gamma function. Moreover, the related Fokker
      Planck equations are given for the Boltzmann, Tsallis, and gamma probability
      distributions. 

PMID- 25768456
TI  - Third law of thermodynamics as a key test of generalized entropies.
AB  - The laws of thermodynamics constrain the formulation of statistical mechanics at
      the microscopic level. The third law of thermodynamics states that the entropy
      must vanish at absolute zero temperature for systems with nondegenerate ground
      states in equilibrium. Conversely, the entropy can vanish only at absolute zero
      temperature. Here we ask whether or not generalized entropies satisfy this
      fundamental property. We propose a direct analytical procedure to test if a
      generalized entropy satisfies the third law, assuming only very general
      assumptions for the entropy S and energy U of an arbitrary N-level classical
      system. Mathematically, the method relies on exact calculation of beta=dS/dU in
      terms of the microstate probabilities p(i). To illustrate this approach, we
      present exact results for the two best known generalizations of statistical
      mechanics. Specifically, we study the Kaniadakis entropy S(kappa), which is
      additive, and the Tsallis entropy S(q), which is nonadditive. We show that the
      Kaniadakis entropy correctly satisfies the third law only for -1<kappa<+1,
      thereby shedding light on why kappa is conventionally restricted to this
      interval. Surprisingly, however, the Tsallis entropy violates the third law for
      q<1. Finally, we give a concrete example of the power of our proposed method by
      applying it to a paradigmatic system: the one-dimensional ferromagnetic Ising
      model with nearest-neighbor interactions.

PMID- 25768457
TI  - Competing reaction processes on a lattice as a paradigm for catalyst
      deactivation.
AB  - We mobilize both a generating function approach and the theory of finite Markov
      processes to compute the probability of irreversible absorption of a randomly
      diffusing species on a lattice with competing reaction centers. We consider an N
      site lattice populated by a single deep trap, and N-1 partially absorbing traps
      (absorption probability 0<s<1). The influence of competing reaction centers on
      the probability of reaction at a target site (the deep trap) and the mean walk
      length of the random walker before localization (a measure of the reaction
      efficiency) are computed for different geometries. Both analytic expressions and
      numerical results are given for reactive processes on two-dimensional surfaces of
      Euler characteristic Omega=0 and Omega=2. The results obtained allow a
      characterization of catalyst deactivation processes on planar surfaces and on
      catalyst pellets where only a single catalytic site remains fully active (deep
      trap), the other sites being only partially active as a result of surface
      poisoning. The central result of our study is that the predicted dependence of
      the reaction efficiency on system size N and on s is in qualitative accord with
      previously reported experimental results, notably catalysts exhibiting selective
      poisoning due to surface sites that have different affinities for chemisorption
      of the poisoning agent (e.g., acid zeolite catalysts). Deviations from the
      efficiency of a catalyst with identical sites are quantified, and we find that
      such deviations display a significant dependence on the topological details of
      the surface (for fixed values of N and s we find markedly different results for,
      say, a planar surface and for the polyhedral surface of a catalyst pellet). Our
      results highlight the importance of surface topology for the efficiency of
      catalytic conversion processes on inhomogeneous substrates, and in particular for
      those aimed at industrial applications. From our exact analysis we extract
      results for the two limiting cases s~1 and s~0, corresponding respectively to
      weak and strong catalyst poisoning (decreasing s leads to a monotonic decrease in
      the efficiency of catalytic conversion). The results for the s~0 case are
      relevant for the dual problem of light-energy conversion via trapping of
      excitations in the chlorophyll antenna network. Here, decreasing the probability
      of excitation trapping s at sites other than the target molecule does not result
      in a decrease of the efficiency as in the catalyst case, but rather in enhanced
      efficiency of light-energy conversion, which we characterize in terms of N and s.
      The one-dimensional case and its connection with a modified version of the
      gambler's ruin problem are discussed. Finally, generalizations of our model are
      described briefly. 

PMID- 25768458
TI  - Shear-stress relaxation and ensemble transformation of shear-stress
      autocorrelation functions.
AB  - We revisit the relation between the shear-stress relaxation modulus G(t),
      computed at finite shear strain 0<gamma?1, and the shear-stress autocorrelation
      functions C(t)|(gamma) and C(t)|(tau) computed, respectively, at imposed strain
      gamma and mean stress tau. Focusing on permanent isotropic spring networks it is
      shown theoretically and computationally that in general
      G(t)=C(t)|(tau)=C(t)|(gamma)+G(eq) for t>0 with G(eq) being the static
      equilibrium shear modulus. G(t) and C(t)|(gamma) thus must become different for
      solids and it is impossible to obtain G(eq) alone from C(t)|(gamma) as often
      assumed. We comment briefly on self-assembled transient networks where G(eq)(f)
      must vanish for a finite scission-recombination frequency f. We argue that
      G(t)=C(t)|(tau)=C(t)|(gamma) should reveal an intermediate plateau set by the
      shear modulus G(eq)(f=0) of the quenched network.

PMID- 25768459
TI  - Scaling phenomena driven by inhomogeneous conditions at first-order quantum
      transitions.
AB  - We investigate the effects of smooth inhomogeneities at first-order quantum
      transitions (FOQTs), such as those arising in the presence of a space-dependent
      external field, which smooths out the discontinuities of the low-energy
      properties at the transition. We argue that a universal scaling behavior emerges
      in the space transition region close to the point in which the external field
      takes the value for which the homogeneous system undergoes the FOQT. We verify
      the general theory in two model systems. We consider the quantum Ising chain in
      the ferromagnetic phase and the q-state Potts chain for q=10, investigating the
      scaling behavior which arises in the presence of an additional inhomogeneous
      parallel and transverse magnetic field, respectively. Numerical results are in
      full agreement with the general theory. 

PMID- 25768460
TI  - Active Brownian particles escaping a channel in single file.
AB  - Active particles may happen to be confined in channels so narrow that they cannot
      overtake each other (single-file conditions). This interesting situation reveals
      nontrivial physical features as a consequence of the strong interparticle
      correlations developed in collective rearrangements. We consider a minimal two
      dimensional model for active Brownian particles with the aim of studying the
      modifications introduced by activity with respect to the classical (passive)
      single-file picture. Depending on whether their motion is dominated by
      translational or rotational diffusion, we find that active Brownian particles in
      single file may arrange into clusters that are continuously merging and splitting
      (active clusters) or merely reproduce passive-motion paradigms, respectively. We
      show that activity conveys to self-propelled particles a strategic advantage for
      trespassing narrow channels against external biases (e.g., the gravitational
      field). 

PMID- 25768461
TI  - Thermodynamic Casimir effect in films: the exchange cluster algorithm.
AB  - We study the thermodynamic Casimir force for films with various types of boundary
      conditions and the bulk universality class of the three-dimensional Ising model.
      To this end, we perform Monte Carlo simulations of the improved Blume-Capel model
      on the simple cubic lattice. In particular, we employ the exchange or geometric
      cluster cluster algorithm [Heringa and Blote, Phys. Rev. E 57, 4976 (1998)]. In a
      previous work, we demonstrated that this algorithm allows us to compute the
      thermodynamic Casimir force for the plate-sphere geometry efficiently. It turns
      out that also for the film geometry a substantial reduction of the statistical
      error can achieved. Concerning physics, we focus on (O,O) boundary conditions,
      where O denotes the ordinary surface transition. These are implemented by free
      boundary conditions on both sides of the film. Films with such boundary
      conditions undergo a phase transition in the universality class of the two
      dimensional Ising model. We determine the inverse transition temperature for a
      large range of thicknesses L(0) of the film and study the scaling of this
      temperature with L(0). In the neighborhood of the transition, the thermodynamic
      Casimir force is affected by finite size effects, where finite size refers to a
      finite transversal extension L of the film. We demonstrate that these finite size
      effects can be computed by using the universal finite size scaling function of
      the free energy of the two-dimensional Ising model.

PMID- 25768462
TI  - Thermodynamic properties of supercritical carbon dioxide: Widom and Frenkel
      lines.
AB  - Supercritical fluids are widely used in a number of important technological
      applications, yet the theoretical progress in the field has been rather moderate.
      Fairly recently, a new understanding of the liquidlike and gaslike properties of
      supercritical fluids has come to the fore, particularly with the advent of the
      Widom and Frenkel lines that aim to demarcate different physical properties on
      the phase diagram. Here, we report the results of a computational study of
      supercritical carbon dioxide, one of the most important fluids in the chemical
      industry. We study the response functions of CO_{2} in the supercritical state
      and calculate the locations of their maxima (Widom lines). We also report the
      preliminary calculations of the Frenkel line, the line of crossover of
      microscopic dynamics of particles. Our insights are relevant to physical
      processes in the atmosphere of Venus and its evolution. 

PMID- 25768463
TI  - Complete graph asymptotics for the Ising and random-cluster models on five
      dimensional grids with a cyclic boundary.
AB  - The finite-size scaling behavior for the Ising model in five dimensions, with
      either free or cyclic boundary, has been the subject of a long-running debate.
      The older papers have been based on ideas from, e.g., field theory or
      renormalization. In this paper we propose a detailed and exact scaling picture
      for critical region of the model with cyclic boundary. Unlike the previous papers
      our approach is based on a comparison with the existing exact and rigorous
      results for the FK-random-cluster model on a complete graph. Based on those
      results we predict several distinct scaling regions in an L-dependent window
      around the critical point. We test these predictions by comparing with data from
      Monte Carlo simulations and find a good agreement. The main feature which differs
      between the complete graph and the five-dimensional model with free boundary is
      the existence of a bimodal energy distribution near the critical point in the
      latter. This feature was found by the same authors in an earlier paper in the
      form of a quasi-first-order phase transition for the same Ising model. 

PMID- 25768464
TI  - Active polymer translocation in the three-dimensional domain.
AB  - In this work we study the translocation process of a polymer through a
      nanochannel where a time dependent force is acting. Two conceptually different
      types of driving are used: a deterministic sinusoidal one and a random telegraph
      noise force. The mean translocation time presents interesting resonant minima as
      a function of the frequency of the external driving. For the computed sizes, the
      translocation time scales with the polymer length according to a power law with
      the same exponent for almost all the frequencies of the two driving forces. The
      dependence of the translocation time with the polymer rigidity, which accounts
      for the persistence length of the molecule, shows a different low frequency
      dependence for the two drivings. 

PMID- 25768465
TI  - Stochastic thermodynamics of a tagged particle within a harmonic chain.
AB  - We study the stochastic thermodynamics of an overdamped harmonic chain, which can
      be viewed equivalently as a one-dimensional Rouse chain or as an approximate
      model of single file diffusion. We discuss mainly two levels of description of
      this system: the Markovian level for which the trajectories of all the particles
      of the chain are known and the non-Markovian level in which only the motion of a
      tagged particle is available. For each case, we analyze the energy dissipation
      and its dependence on initial conditions. Surprisingly, we find that the average
      coarse-grained entropy production rate can become transiently negative when an
      oscillating force is applied to the tagged particle. This occurs due to memory
      effects as shown in a framework based on path integrals or on a generalized
      Langevin equation. 

PMID- 25768466
TI  - Exact results for a noise-induced bistable system.
AB  - A stochastic system where bistability is caused by noise has been recently
      investigated by Biancalani et al. [Phys. Rev. Lett. 112, 038101 (2014)]. They
      have computed the mean switching time for such a system using a continuous Fokker
      Planck equation derived from the Taylor expansion of the master equation to
      estimate the parameter of such a system from experiment. In this article, we
      provide the exact solution for the full discrete system without resorting to
      continuous approximation and obtain the expression for the mean switching time.
      We further extend this investigation by solving exactly the master equation and
      obtaining the expression of other quantities of interests such as the dynamics of
      the moments and the equilibrium time.

PMID- 25768467
TI  - Scaling of the spanning threshold in gradient percolation.
AB  - A simple and fast way to apply correlations in percolation simulations is to
      apply a uniform gradient to the occupancy probabilities. For small networks,
      exact results are presented here for the spanning thresholds in site percolation
      with a gradient for networks up to 4*4 in two dimensions and 2*2*2 in three
      dimensions. Numerical results are provided for larger networks that extrapolate
      to a linear modification of the threshold proportional to the gradient for
      moderate values of the gradient. 

PMID- 25768468
TI  - Optimal recruitment strategies for groups of interacting walkers with leaders.
AB  - We introduce a model of interacting random walkers on a finite one-dimensional
      chain with absorbing boundaries or targets at the ends. Walkers are of two types:
      informed particles that move ballistically towards a given target and diffusing
      uninformed particles that are biased towards close informed individuals. This
      model mimics the dynamics of hierarchical groups of animals, where an informed
      individual tries to persuade and lead the movement of its conspecifics. We
      characterize the success of this persuasion by the first-passage probability of
      the uninformed particle to the target, and we interpret the speed of the informed
      particle as a strategic parameter that the particle can tune to maximize its
      success. We find that the success probability is nonmonotonic, reaching its
      maximum at an intermediate speed whose value increases with the diffusing rate of
      the uninformed particle. When two different groups of informed leaders traveling
      in opposite directions compete, usually the largest group is the most successful.
      However, the minority can reverse this situation and become the most probable
      winner by following two different strategies: increasing its attraction strength
      or adjusting its speed to an optimal value relative to the majority's speed. 

PMID- 25768469
TI  - Scaling behavior near jamming in random sequential adsorption.
AB  - For the random sequential adsorption model, we introduce the "availability" as a
      variable corresponding to the number of available locations in which an adsorbate
      can be accommodated. We investigate the relation of the availability to the
      coverage of the adsorbent surface over time. Power law scaling between the two is
      obtained both through numerical simulations and analytical techniques for both
      one- and two-dimensional random sequential adsorption, as well as in the case of
      competitive random sequential adsorption in one dimension. 

PMID- 25768470
TI  - Exactly solvable model of a coalescing random graph.
AB  - An initially empty (no edges) graph of order M evolves by randomly adding one
      edge at a time. This edge connects either two linked components and forms a new
      component of larger order (coalescence of graphs) or increases (by one) the
      number of edges in a given linked component (cycling). Assuming that the vertices
      of the graph have a finite valence (the number of edges connected with a given
      vertex is limited) the kinetic equation for the distribution of linked components
      of the graph over their orders and valences is formulated and solved by applying
      the generating function method. The evolution process is shown to reveal a phase
      transition: the emergence of a giant linked component whose order is comparable
      to the total order of the graph. The kinetics of growth of this component is
      studied for arbitrary initial conditions. Found are the time dependences of the
      average order and the valence of the giant component. The distribution over
      orders and valences of the linked components of the graph is derived for an
      initially empty graph comprising M bare polyvalent vertices. 

PMID- 25768471
TI  - Understanding the ideal glass transition: lessons from an equilibrium study of
      hard disks in a channel.
AB  - We use an exact transfer-matrix approach to compute the equilibrium properties of
      a system of hard disks of diameter sigma confined to a two-dimensional channel of
      width 1.95sigma at constant longitudinal applied force. At this channel width,
      which is sufficient for next-nearest-neighbor disks to interact, the system is
      known to have a great many jammed states. Our calculations show that the
      longitudinal force (pressure) extrapolates to infinity at a well-defined packing
      fraction phi(K) that is less than the maximum possible phi(max), the latter
      corresponding to a buckled crystal. In this quasi-one-dimensional problem there
      is no question of there being any real divergence of the pressure at phi(K). We
      give arguments that this avoided phase transition is a structural feature, the
      remnant in our narrow channel system of the hexatic to crystal transition, but
      that it has the phenomenology of the (avoided) ideal glass transition. We
      identify a length scale xi(3) as our equivalent of the penetration length for
      amorphous order: In the channel system, it reaches a maximum value of around
      15sigma at phi(K), which is larger than the penetration lengths that have been
      reported for three-dimensional systems. It is argued that the alpha-relaxation
      time would appear on extrapolation to diverge in a Vogel-Fulcher manner as the
      packing fraction approaches phi(K).

PMID- 25768472
TI  - Peer pressure: enhancement of cooperation through mutual punishment.
AB  - An open problem in evolutionary game dynamics is to understand the effect of peer
      pressure on cooperation in a quantitative manner. Peer pressure can be modeled by
      punishment, which has been proved to be an effective mechanism to sustain
      cooperation among selfish individuals. We investigate a symmetric punishment
      strategy, in which an individual will punish each neighbor if their strategies
      are different, and vice versa. Because of the symmetry in imposing the
      punishment, one might intuitively expect the strategy to have little effect on
      cooperation. Utilizing the prisoner's dilemma game as a prototypical model of
      interactions at the individual level, we find, through simulation and theoretical
      analysis, that proper punishment, when even symmetrically imposed on individuals,
      can enhance cooperation. Also, we find that the initial density of cooperators
      plays an important role in the evolution of cooperation driven by mutual
      punishment. 

PMID- 25768473
TI  - Quantum spherical spins with local symmetry.
AB  - We construct a quantum system of spherical spins with a continuous local
      symmetry. The model is exactly soluble in the thermodynamic limit and exhibits a
      number of interesting properties. We show that the local symmetry is
      spontaneously broken at finite as well as zero temperatures, implying the
      existence of classical and quantum phase transitions with a nontrivial critical
      behavior. The dynamical generation of gauge fields and the equivalence with the
      CP((N-1)) model in the limit N->infinity are investigated. The dynamical
      generation of gauge fields is a consequence of the restoration of the local
      symmetry.

PMID- 25768474
TI  - Extreme-value statistics of work done in stretching a polymer in a gradient flow.
AB  - We analyze the statistics of work generated by a gradient flow to stretch a
      nonlinear polymer. We obtain the large deviation function (LDF) of the work in
      the full range of appropriate parameters by combining analytical and numerical
      tools. The LDF shows two distinct asymptotes: "near tails" are linear in work and
      dominated by coiled polymer configurations, while "far tails" are quadratic in
      work and correspond to preferentially fully stretched polymers. We find the
      extreme value statistics of work for several singular elastic potentials, as well
      as the mean and the dispersion of work near the coil-stretch transition. The
      dispersion shows a maximum at the transition. 

PMID- 25768475
TI  - Translational diffusion of water inside hydrophobic carbon micropores studied by
      neutron spectroscopy and molecular dynamics simulation.
AB  - When water molecules are confined to nanoscale spacings, such as in the nanometer
      size pores of activated carbon fiber (ACF), their freezing point gets suppressed
      down to very low temperatures (~150K), leading to a metastable liquid state with
      remarkable physical properties. We have investigated the ambient pressure
      diffusive dynamics of water in microporous Kynol ACF-10 (average pore size
      ~11.6A, with primarily slit-like pores) from temperature T=280 K in its stable
      liquid state down to T=230 K into the metastable supercooled phase. The observed
      characteristic relaxation times and diffusion coefficients are found to be,
      respectively, higher and lower than those in bulk water, indicating a slowing
      down of the water mobility with decreasing temperature. The observed temperature
      dependent average relaxation time <tau> when compared to previous findings
      indicate that it is the width of the slit pores-not their curvature-that
      primarily affects the dynamics of water for pore sizes larger than 10 A. The
      experimental observations are compared to complementary molecular dynamics
      simulations of a model system, in which we studied the diffusion of water within
      the 11.6 A gap of two parallel graphene sheets. We find generally a reasonable
      agreement between the observed and calculated relaxation times at the low
      momentum transfer Q(Q<=0.9A(-1)). At high Q, however, where localized dynamics
      becomes relevant, this ideal system does not satisfactorily reproduce the
      measurements. Consequently, the simulations are compared to the experiments at
      low Q, where the two can be best reconciled. The best agreement is obtained for
      the diffusion parameter D associated with the hydrogen-site when a representative
      stretched exponential function, rather than the standard bimodal exponential
      model, is used to parametrize the self-correlation function I(Q,t).

PMID- 25768476
TI  - Emergence of jams in the generalized totally asymmetric simple exclusion process.
AB  - The generalized totally asymmetric exclusion process (TASEP) [J. Stat. Mech.
      (2012) P05014] is an integrable generalization of the TASEP equipped with an
      interaction, which enhances the clustering of particles. The process interpolates
      between two extremal cases: the TASEP with parallel update and the process with
      all particles irreversibly merging into a single cluster moving as an isolated
      particle. We are interested in the large time behavior of this process on a ring
      in the whole range of the parameter lambda controlling the interaction. We study
      the stationary state correlations, the cluster size distribution, and the large
      time fluctuations of integrated particle current. When lambda is finite, we find
      the usual TASEP-like behavior: The correlation length is finite; there are only
      clusters of finite size in the stationary state and current fluctuations belong
      to the Kardar-Parisi-Zhang universality class. When lambda grows with the system
      size, so does the correlation length. We find a nontrivial transition regime with
      clusters of all sizes on the lattice. We identify a crossover parameter and
      derive the large deviation function for particle current, which interpolates
      between the case considered by Derrida-Lebowitz and a single-particle diffusion.

PMID- 25768477
TI  - Fluctuations of work in nearly adiabatically driven open quantum systems.
AB  - We extend the quantum jump method to nearly adiabatically driven open quantum
      systems in a way that allows for an accurate account of the external driving in
      the system-environment interaction. Using this framework, we construct the
      corresponding trajectory-dependent work performed on the system and derive the
      integral fluctuation theorem and the Jarzynski equality for nearly adiabatic
      driving. We show that such identities hold as long as the stochastic dynamics and
      work variable are consistently defined. We numerically study the emerging work
      statistics for a two-level quantum system and find that the conventional diabatic
      approximation is unable to capture some prominent features arising from driving,
      such as the continuity of the probability density of work. Our results reveal the
      necessity of using accurate expressions for the drive-dressed heat exchange in
      future experiments probing jump time distributions. 

PMID- 25768478
TI  - Anomalous velocity fluctuation in one-dimensional defect turbulence.
AB  - In this paper various eccentric hole dynamics are presented in defect turbulence
      of the one-dimensional complex Ginzburg-Landau equation. Each hole shows coherent
      particlelike motion with nonconstant velocity. On the other hand, successive hole
      velocities without discriminating each hole exhibit anomalous intermittent
      motions being subject to multi-time-scale non-Gaussian statistics. An alternate
      non-Markov stochastic differential equation is proposed, by which all these
      observed statistical properties can be described successfully. 

PMID- 25768479
TI  - Friction and noise for a probe in a nonequilibrium fluid.
AB  - We investigate the fluctuation dynamics of a probe around a deterministic motion
      induced by interactions with driven particles. The latter constitute the
      nonequilibrium medium in which the probe is immersed and is modeled as overdamped
      Langevin particle dynamics driven by nonconservative forces. The expansion that
      yields the friction and noise expressions for the reduced probe dynamics is based
      on linear response around a time-dependent nonequilibrium condition of the
      medium. The result contains an extension of the second fluctuation-dissipation
      relation between friction and noise for probe motion in a nonequilibrium fluid. 

PMID- 25768480
TI  - Exact finite-size corrections for the spanning-tree model under different
      boundary conditions.
AB  - We express the partition functions of the spanning tree on finite square lattices
      under five different sets of boundary conditions in terms of a principal
      partition function with twisted-boundary conditions. Based on these expressions,
      we derive the exact asymptotic expansions of the logarithm of the partition
      function for each case. We have also established several groups of identities
      relating spanning-tree partition functions for the different boundary conditions.
      We also explain an apparent discrepancy between logarithmic correction terms in
      the free energy for a two-dimensional spanning-tree model with periodic and free
      boundary conditions and conformal field theory predictions. We have obtained
      corner free energy for the spanning tree under free-boundary conditions in full
      agreement with conformal field theory predictions. 

PMID- 25768481
TI  - Brownian dynamics: from glassy to trivial.
AB  - We endow a system of interacting particles with two distinct, local, Markovian,
      and reversible microscopic dynamics that both converge to the Boltzmann-Gibbs
      equilibrium of standard liquids. While the first, standard, one leads to glassy
      dynamics, we use field-theoretical techniques to show that the latter displays no
      sign of glassiness. The approximations we use, akin to the mode-coupling
      approximation, are famous for magnifying glassy aspects of the dynamics,
      supposedly through the neglect of activated events. Despite this, the modified
      dynamics seem to stick to standard liquid relaxation. This finding singles out as
      applying to a realistic system of interacting particles in low dimensions and
      questions the role of the dynamical rules used to explore a given static free
      energy landscape. Moreover, our peculiar choice of dynamical rules offers the
      possibility of a direct connection with replica theory, and our findings
      therefore call for a clarification of the interplay between replica theory and
      the underlying dynamics of the system. 

PMID- 25768482
TI  - Asymptotic densities of ballistic Levy walks.
AB  - We propose an analytical method to determine the shape of density profiles in the
      asymptotic long-time limit for a broad class of coupled continuous-time random
      walks which operate in the ballistic regime. In particular, we show that
      different scenarios of performing a random-walk step, via making an instantaneous
      jump penalized by a proper waiting time or via moving with a constant speed,
      dramatically effect the corresponding propagators, despite the fact that the end
      points of the steps are identical. Furthermore, if the speed during each step of
      the random walk is itself a random variable, its distribution gets clearly
      reflected in the asymptotic density of random walkers. These features are in
      contrast with more standard nonballistic random walks. 

PMID- 25768483
TI  - Fourier Monte Carlo renormalization-group approach to crystalline membranes.
AB  - The computation of the critical exponent eta characterizing the universal elastic
      behavior of crystalline membranes in the flat phase continues to represent
      challenges to theorists as well as computer simulators that manifest themselves
      in a considerable spread of numerical results for eta published in the
      literature. We present additional insight into this problem that results from
      combining Wilson's momentum shell renormalization-group method with the power of
      modern computer simulations based on the Fourier Monte Carlo algorithm. After
      discussing the ideas and difficulties underlying this combined scheme, we present
      a calculation of the renormalization-group flow of the effective two-dimensional
      Young modulus for momentum shells of different thickness. Extrapolation to
      infinite shell thickness allows us to produce results in reasonable agreement
      with those obtained by functional renormalization group or by Fourier Monte Carlo
      simulations in combination with finite-size scaling. Moreover, our method allows
      us to obtain a decent estimate for the value of the Wegner exponent omega that
      determines the leading correction to scaling, which in turn allows us to refine
      our numerical estimate for eta previously obtained from precise finite-size
      scaling data. 

PMID- 25768484
TI  - Energy landscape of the finite-size mean-field 2-spin spherical model and
      topology trivialization.
AB  - Motivated by the recently observed phenomenon of topology trivialization of
      potential energy landscapes (PELs) for several statistical mechanics models, we
      perform a numerical study of the finite-size 2-spin spherical model using both
      numerical polynomial homotopy continuation and a reformulation via non-Hermitian
      matrices. The continuation approach computes all of the complex stationary points
      of this model while the matrix approach computes the real stationary points.
      Using these methods, we compute the average number of stationary points while
      changing the topology of the PEL as well as the variance. Histograms of these
      stationary points are presented along with an analysis regarding the complex
      stationary points. This work connects topology trivialization to two different
      branches of mathematics: algebraic geometry and catastrophe theory, which is
      fertile ground for further interdisciplinary research. 

PMID- 25768485
TI  - Vigorous thermal excitations in a double-tetrahedral chain of localized Ising
      spins and mobile electrons mimic a temperature-driven first-order phase
      transition.
AB  - A hybrid spin-electron system defined on a one-dimensional double-tetrahedral
      chain, in which the localized Ising spin regularly alternates with two mobile
      electrons delocalized over a triangular plaquette, is exactly solved with the
      help of generalized decoration-iteration transformation. It is shown that a
      macroscopic degeneracy of ferromagnetic and ferrimagnetic ground states arising
      from chiral degrees of freedom of the mobile electrons cannot be lifted by a
      magnetic field in contrast to a macroscopic degeneracy of the frustrated ground
      state, which appears due to a kinetically driven frustration of the localized
      Ising spins. An anomalous behavior of all basic thermodynamic quantities can be
      observed on account of massive thermal excitations, which mimic a temperature
      driven first-order phase transition from the nondegenerate frustrated state to
      the highly degenerate ferrimagnetic state at nonzero magnetic fields. A
      substantial difference in the respective degeneracies is responsible for an
      immense low-temperature peak of the specific heat and very abrupt (almost
      discontinuous) thermal variations of the entropy and sublattice magnetizations. 

PMID- 25768486
TI  - Consistent thermodynamic framework for interacting particles by neglecting
      thermal noise.
AB  - An effective temperature theta, conjugated to a generalized entropy s(q), was
      introduced recently for a system of interacting particles. Since theta presents
      values much higher than those of typical room temperatures T?theta, the thermal
      noise can be neglected (T/theta?0) in these systems. Moreover, the consistency of
      this definition, as well as of a form analogous to the first law of
      thermodynamics, du=thetads(q)+deltaW, were verified lately by means of a Carnot
      cycle, whose efficiency was shown to present the usual form, eta=1
      (theta(2)/theta(1)). Herein we explore further the heat contribution
      deltaQ=thetads(q) by proposing a way for a heat exchange between two such
      systems, as well as its associated thermal equilibrium. As a consequence, the
      zeroth principle is also established. Moreover, we consolidate the first-law
      proposal by following the usual procedure for obtaining different potentials,
      i.e., applying Legendre transformations for distinct pairs of independent
      variables. From these potentials we derive the equation of state, Maxwell
      relations, and define response functions. All results presented are shown to be
      consistent with those of standard thermodynamics for T>0.

PMID- 25768487
TI  - Constitutive relation for nonlinear response and universality of efficiency at
      maximum power for tight-coupling heat engines.
AB  - We present a unified perspective on nonequilibrium heat engines by generalizing
      nonlinear irreversible thermodynamics. For tight-coupling heat engines, a generic
      constitutive relation for nonlinear response accurate up to the quadratic order
      is derived from the stalling condition and the symmetry argument. By applying
      this generic nonlinear constitutive relation to finite-time thermodynamics, we
      obtain the necessary and sufficient condition for the universality of efficiency
      at maximum power, which states that a tight-coupling heat engine takes the
      universal efficiency at maximum power up to the quadratic order if and only if
      either the engine symmetrically interacts with two heat reservoirs or the
      elementary thermal energy flowing through the engine matches the characteristic
      energy of the engine. Hence we solve the following paradox: On the one hand, the
      quadratic term in the universal efficiency at maximum power for tight-coupling
      heat engines turned out to be a consequence of symmetry [Esposito, Lindenberg,
      and Van den Broeck, Phys. Rev. Lett. 102, 130602 (2009); Sheng and Tu, Phys. Rev.
      E 89, 012129 (2014)]; On the other hand, typical heat engines such as the Curzon
      Ahlborn endoreversible heat engine [Curzon and Ahlborn, Am. J. Phys. 43, 22
      (1975)] and the Feynman ratchet [Tu, J. Phys. A 41, 312003 (2008)] recover the
      universal efficiency at maximum power regardless of any symmetry.

PMID- 25768488
TI  - Nonextensive thermodynamic functions in the Schrodinger-Gibbs ensemble.
AB  - Schrodinger suggested that thermodynamical functions cannot be based on the
      gratuitous allegation that quantum-mechanical levels (typically the orthogonal
      eigenstates of the Hamiltonian operator) are the only allowed states for a
      quantum system [E. Schrodinger, Statistical Thermodynamics (Courier Dover,
      Mineola, 1967)]. Different authors have interpreted this statement by introducing
      density distributions on the space of quantum pure states with weights obtained
      as functions of the expectation value of the Hamiltonian of the system. In this
      work we focus on one of the best known of these distributions and prove that,
      when considered in composite quantum systems, it defines partition functions that
      do not factorize as products of partition functions of the noninteracting
      subsystems, even in the thermodynamical regime. This implies that it is not
      possible to define extensive thermodynamical magnitudes such as the free energy,
      the internal energy, or the thermodynamic entropy by using these models.
      Therefore, we conclude that this distribution inspired by Schrodinger's idea
      cannot be used to construct an appropriate quantum equilibrium thermodynamics. 

PMID- 25768489
TI  - Phase diagram of fluid phases in (3)He-(4)He mixtures.
AB  - Fluid parts of the phase diagram of (3)He-(4)He mixtures are obtained from a mean
      field analysis of a suitable lattice gas model for binary liquid mixtures. The
      proposed model takes into account the continuous rotational symmetry O(2) of the
      superfluid degrees of freedom associated with (4)He and includes the occurrence
      of vacancies. This latter degree of freedom allows the model to exhibit a vapor
      phase and hence can provide the theoretical framework to describe the
      experimental conditions for measurements of tricritical Casimir forces in (3)He
      (4)He wetting films.

PMID- 25768490
TI  - Harmonically bound Brownian motion in fluids under shear: Fokker-Planck and
      generalized Langevin descriptions.
AB  - We study the Brownian motion of a particle bound by a harmonic potential and
      immersed in a fluid with a uniform shear flow. We describe this problem first in
      terms of a linear Fokker-Planck equation which is solved to obtain the
      probability distribution function for finding the particle in a volume element of
      its associated phase space. We find the explicit form of this distribution in the
      stationary limit and use this result to show that both the equipartition law and
      the equation of state of the trapped particle are modified from their equilibrium
      form by terms increasing as the square of the imposed shear rate. Subsequently,
      we propose an alternative description of this problem in terms of a generalized
      Langevin equation that takes into account the effects of hydrodynamic
      correlations and sound propagation on the dynamics of the trapped particle. We
      show that these effects produce significant changes, manifested as long-time
      tails and resonant peaks, in the equilibrium and nonequilibrium correlation
      functions for the velocity of the Brownian particle. We implement numerical
      simulations based on molecular dynamics and multiparticle collision dynamics, and
      observe a very good quantitative agreement between the predictions of the model
      and the numerical results, thus suggesting that this kind of numerical
      simulations could be used as complement of current experimental techniques. 

PMID- 25768491
TI  - Leaf-excluded percolation in two and three dimensions.
AB  - We introduce the leaf-excluded percolation model, which corresponds to
      independent bond percolation conditioned on the absence of leaves (vertices of
      degree one). We study the leaf-excluded model on the square and simple-cubic
      lattices via Monte Carlo simulation, using a worm-like algorithm. By studying
      wrapping probabilities, we precisely estimate the critical thresholds to be
      0.3552475(8) (square) and 0.185022(3) (simple-cubic). Our estimates for the
      thermal and magnetic exponents are consistent with those for percolation,
      implying that the phase transition of the leaf-excluded model belongs to the
      standard percolation universality class. 

PMID- 25768492
TI  - Origin of a depth-independent drag force induced by stirring in granular media.
AB  - Experiments have shown that when a horizontal cylinder rotates around the
      vertical axis in a granular medium, the drag force in the stationary regime
      becomes independent of the depth, in contradiction with the frictional picture
      stipulating that the drag should be proportional to the hydrostatic pressure. The
      goal of this study is to understand the origin of this depth independence of the
      granular drag. Intensive numerical simulations using the discrete element method
      are performed giving access to the stress distribution in the packing during the
      rotation of the cylinder. It is shown that the rotation induces a strong
      anisotropy in the stress distribution, leading to the formation of arches that
      screen the hydrostatic pressure in the vicinity of the cylinder and create a
      bubble of low pressure. 

PMID- 25768493
TI  - Penetration depth scaling for impact into wet granular packings.
AB  - We present experimental measurements of penetration depths for the impact of
      spheres into wetted granular media. We observe that the penetration depth in the
      liquid saturated case scales with projectile density, size, and drop height in a
      fashion consistent with the scaling observed in the dry case, but with smaller
      penetrations. Neither viscous drag nor density effects can explain the
      enhancement to the stopping force. The penetration depth exhibits a complicated
      dependence on liquid fraction, accompanied by a change in the drop-height
      dependence, that must be the consequence of accompanying changes in the
      conformation of the liquid phase in the interstices. 

PMID- 25768494
TI  - Bonded-cell model for particle fracture.
AB  - Particle degradation and fracture play an important role in natural granular
      flows and in many applications of granular materials. We analyze the fracture
      properties of two-dimensional disklike particles modeled as aggregates of rigid
      cells bonded along their sides by a cohesive Mohr-Coulomb law and simulated by
      the contact dynamics method. We show that the compressive strength scales with
      tensile strength between cells but depends also on the friction coefficient and a
      parameter describing cell shape distribution. The statistical scatter of
      compressive strength is well described by the Weibull distribution function with
      a shape parameter varying from 6 to 10 depending on cell shape distribution. We
      show that this distribution may be understood in terms of percolating critical
      intercellular contacts. We propose a random-walk model of critical contacts that
      leads to particle size dependence of the compressive strength in good agreement
      with our simulation data. 

PMID- 25768495
TI  - Numerical investigation of the cylinder movement in granular matter.
AB  - We investigate numerically the mechanisms governing horizontal dragging of a
      rigid cylinder buried inside granular matter, with particular emphasis on
      enumerating drag and lift forces that resist cylinder movement. The recently
      proposed particle finite element method is employed, which combines the
      robustness of classical continuum mechanics formulations in terms of representing
      complex aspects of the material constitutive behavior, with the effectiveness of
      discrete element methods in simulating ultralarge deformation problems. The
      investigation focuses on the effect of embedment depth, cylinder roughness,
      granular matter macromechanical properties, and of the magnitude of the
      cylinder's horizontal displacement on the amplitude of the resisting forces,
      which are discussed in light of published experimental data. Interpretation of
      the results provides insight on how the material flow around the cylinder affects
      the developing resistance, and a mechanism is proposed to describe the
      development of a steady-state drag force at large horizontal movements of the
      cylinder. 

PMID- 25768496
TI  - Sound pulse broadening in stressed granular media.
AB  - The pulse broadening and decay of coherent sound waves propagating in disordered
      granular media are investigated. We find that the pulse width of these
      compressional waves is broadened when the disorder is increased by mixing the
      beads made of different materials. To identify the responsible mechanism for the
      pulse broadening, we also perform the acoustic attenuation measurement by
      spectral analysis and the numerical simulation of pulsed sound wave propagation
      along one-dimensional disordered elastic chains. The qualitative agreement
      between experiment and simulation reveals a dominant mechanism by scattering
      attenuation at the high-frequency range, which is consistent with theoretical
      models of sound wave scattering in strongly random media via a correlation
      length. 

PMID- 25768497
TI  - Phase transition and flow-rate behavior of merging granular flows.
AB  - Merging of granular flows is ubiquitous in industrial, mining, and geological
      processes. However, its behavior remains poorly understood. This paper studies
      the phase transition and flow-rate behavior of two granular flows merging into
      one channel. When the main channel is wider than the side channel, the system
      shows a remarkable two-sudden-drops phenomenon in the outflow rate when gradually
      increasing the main inflow. When gradually decreasing the main inflow, the system
      shows obvious hysteresis phenomenon. We study the flow-rate-drop phenomenon by
      measuring the area fraction and the mean velocity at the merging point. The phase
      diagram of the system is also presented to understand the occurrence of the
      phenomenon. We find that the dilute-to-dense transition occurs when the area
      fraction of particles at the joint point exceeds a critical value phi(c)=0.65+/
      0.03.

PMID- 25768498
TI  - Statistics of conserved quantities in mechanically stable packings of
      frictionless disks above jamming.
AB  - We numerically simulate mechanically stable packings of soft-core, frictionless,
      bidisperse disks in two dimensions, above the jamming packing fraction phi(J).
      For configurations with a fixed isotropic global stress tensor, we compute the
      averages, variances, and correlations of conserved quantities (stress Gamma(C),
      force-tile area A(C), Voronoi volume V(C), number of particles N(C), and number
      of small particles N(sC)) on compact subclusters of particles C, as a function of
      the cluster size and the global system stress. We find several significant
      differences depending on whether the cluster C is defined by a fixed radius R or
      a fixed number of particles M. We comment on the implications of our findings for
      maximum entropy models of jammed packings.

PMID- 25768499
TI  - Inherent structures, fragility, and jamming: insights from quasi-one-dimensional
      hard disks.
AB  - We study a quasi-one-dimensional system of hard disks confined between hard lines
      to explore the relationship between the inherent structure landscape, the
      thermodynamics, and the dynamics of the fluid. The transfer matrix method is used
      to obtain an exact description of the landscape, equation of state, and provide a
      mapping of configurations of the equilibrium fluid to their local jammed
      structures. This allows us to follow how the system samples the landscape as a
      function of occupied volume fraction phi. Configurations of the ideal gas map to
      the maximum in the distribution of inherent structures, with a jamming volume
      fraction phi(J)(*), and sample more dense basins with increasing phi. This
      suggests jammed states with a density below phi(J)(*) are inaccessible from the
      equilibrium fluid. The configurational entropy of the fluid decreases rapidly at
      intermediate phi before plateauing at a low value and going to zero as the most
      dense packing is approached. This leads to the appearance of a maximum in both
      the isobaric heat capacity and the inherent structure pressure. We also show that
      the system exhibits a crossover from fragile to strong fluid behavior, located at
      the heat capacity maximum. Structural relaxation in the fragile fluid is shown to
      be controlled by the presence of high order saddle points caused by neighboring
      defects that are unstable with respect to jamming and spontaneously rearrange to
      form a stable local environment. In the strong fluid, the defect concentration is
      low so that defects do not interact and relaxation occurs through the hopping of
      isolated defects between stable local packing environments.

PMID- 25768500
TI  - Significance of thermal fluctuations and hydrodynamic interactions in receptor
      ligand-mediated adhesive dynamics of a spherical particle in wall-bound shear
      flow.
AB  - The dynamics of adhesion of a spherical microparticle to a ligand-coated wall, in
      shear flow, is studied using a Langevin equation that accounts for thermal
      fluctuations, hydrodynamic interactions, and adhesive interactions. Contrary to
      the conventional assumption that thermal fluctuations play a negligible role at
      high Peclet numbers, we find that for particles with low surface densities of
      receptors, rotational diffusion caused by fluctuations about the flow and
      gradient directions aids in bond formation, leading to significantly greater
      adhesion on average, compared to simulations where thermal fluctuations are
      completely ignored. The role of wall hydrodynamic interactions on the steady
      state motion of a particle, when the particle is close to the wall, has also been
      explored. At high Peclet numbers, the shear induced force that arises due to the
      stresslet part of the Stokes dipole plays a dominant role, reducing the particle
      velocity significantly and affecting the states of motion of the particle. The
      coupling between the translational and rotational degrees of freedom of the
      particle, brought about by the presence of hydrodynamic interactions, is found to
      have no influence on the binding dynamics. On the other hand, the drag
      coefficient, which depends on the distance of the particle from the wall, plays a
      crucial role at low rates of bond formation. A significant difference in the
      effect of both the shear force and the position-dependent drag force on the
      states of motion of the particle is observed when the Peclet number is small. 

PMID- 25768501
TI  - Electrophoresis of electrically neutral porous spheres induced by selective
      affinity of ions.
AB  - I investigate the possibility that electrically neutral porous spheres
      electrophorese in electrolyte solutions with asymmetric affinity of ions to
      spheres on the basis of electrohydrodynamics and the Poisson-Boltzmann and Debye
      Bueche-Brinkman theories. Assuming a weak electric field and ignoring the double
      layer polarization, I obtain analytical expressions for electrostatic potential,
      electrophoretic mobility, and flow field. In the equilibrium state, the Galvani
      potential forms across the interface of the spheres. Under a weak electric field,
      the spheres show finite mobility with the same sign as the Galvani potential.
      When the radius of the spheres is significantly larger than the Debye and
      hydrodynamic screening length, the mobility monotonically increases with
      increasing salinity. 

PMID- 25768502
TI  - Dynamic simulation of sediment films of Yukawa-stabilized particles.
AB  - The fast lubrication dynamics method is applied to simulate the motion and
      deposition of charge-stabilized 100-nm-diam particles into sediment films from
      aqueous dispersions. Colloidal interactions are incorporated with a Yukawa
      potential and the effects of the screened-Coulomb potential strength and Peclet
      number (which controls the sedimentation driving force) on particle orientation
      are quantified with a sixfold bond order parameter. The effect of sediment growth
      rate on the order parameter is determined and related to a competition between
      the electrostatic interaction strength and sedimentation driving force.
      Increasing the electrostatic interaction strength and decreasing the Peclet
      number lead to lower sediment growth rates and consequently greater sixfold bond
      order. Our work demonstrates the feasibility of including lubrication
      interactions in dynamic simulations of sediment films and suggests that these
      interactions play a central role in the kinetics of film microstructure
      development and consequently in the degree of order within the film. 

PMID- 25768503
TI  - Swelling of pH-sensitive hydrogels.
AB  - A model is derived for the elastic response of polyelectrolyte gels subjected to
      unconstrained and constrained swelling. A gel is treated as a three-phase medium
      consisting of a solid phase (polymer network), solvent (water), and solutes
      (mobile ions). Transport of solvent and solutes is modeled as their diffusion
      through the network accelerated by an electric field formed by ions and
      accompanied by chemical reactions (dissociation of functional groups attached to
      the chains). Constitutive equations (including the van't Hoff law for ionic
      pressure and the Henderson-Hasselbach equation for ionization of chains) are
      derived by means of the free energy imbalance inequality. Good agreement is
      demonstrated between equilibrium swelling diagrams on several pH-sensitive gels
      and results of simulation. It is revealed that swelling of polyelectrolyte gels
      is driven by electrostatic repulsion of bound charges, whereas the effect of
      ionic pressure is of secondary importance. 

PMID- 25768504
TI  - Active swarms on a sphere.
AB  - We show that coupling to curvature nontrivially affects collective motion in
      active systems, leading to motion patterns not observed in flat space. Using
      numerical simulations, we study a model of self-propelled particles with polar
      alignment and soft repulsion confined to move on the surface of a sphere. We
      observe a variety of motion patterns with the main hallmarks being polar vortex
      and circulating band states arising due to the incompatibility between spherical
      topology and uniform motion-a consequence of the "hairy ball" theorem. We provide
      a detailed analysis of density, velocity, pressure, and stress profiles in the
      circulating band state. In addition, we present analytical results for a
      simplified model of collective motion on the sphere showing that frustration due
      to curvature leads to stable elastic distortions storing energy in the band. 

PMID- 25768505
TI  - Ray-theory approach to electrical-double-layer interactions.
AB  - A novel approach is presented for analyzing the double-layer interaction force
      between charged particles in electrolyte solution, in the limit where the Debye
      length is small compared with both interparticle separation and particle size.
      The method, developed here for two planar convex particles of otherwise arbitrary
      geometry, yields a simple asymptotic approximation limited to neither small zeta
      potentials nor the "close-proximity" assumption underlying Derjaguin's
      approximation. Starting from the nonlinear Poisson-Boltzmann formulation,
      boundary-layer solutions describing the thin diffuse-charge layers are
      asymptotically matched to a WKBJ expansion valid in the bulk, where the potential
      is exponentially small. The latter expansion describes the bulk potential as
      superposed contributions conveyed by "rays" emanating normally from the boundary
      layers. On a special curve generated by the centers of all circles maximally
      inscribed between the two particles, the bulk stress-associated with the ray
      contributions interacting nonlinearly-decays exponentially with distance from the
      center of the smallest of these circles. The force is then obtained by
      integrating the traction along this curve using Laplace's method. We illustrate
      the usefulness of our theory by comparing it, alongside Derjaguin's
      approximation, with numerical simulations in the case of two parallel cylinders
      at low potentials. By combining our result and Derjaguin's approximation, the
      interaction force is provided at arbitrary interparticle separations. Our theory
      can be generalized to arbitrary three-dimensional geometries, nonideal
      electrolyte models, and other physical scenarios where exponentially decaying
      fields give rise to forces. 

PMID- 25768506
TI  - Impact of hydrodynamics on effective interactions in suspensions of active and
      passive matter.
AB  - Passive particles exhibit unique properties when immersed in an active bath of
      self-propelling entities. In particular, an effective attraction can appear
      between particles that repel each other when in a passive solution. Here we
      numerically study the effect of hydrodynamics on an active-passive hybrid system,
      where we observe qualitative differences as compared to simulations with excluded
      volume effects alone. The results shed light on an existing discrepancy in pair
      lifetimes between simulation and experiment, due to the hydrodynamically enhanced
      stability of coupled passive particles. 

PMID- 25768507
TI  - Liquid-vapor interface of the Stockmayer fluid in a uniform external field.
AB  - The effect of a uniform (nonspatially varying) external field on the liquid-vapor
      interface of the Stockmayer fluid (Lennard-Jones particles embedded with a point
      dipole) has been investigated by molecular-dynamics simulations. The long-ranged
      parts of both the dipole and Lennard-Jones interactions are treated using an
      Ewald summation, which removes the effects of the cutoff. The direction of the
      field shifts the critical point and interfacial properties in different
      directions. For an external field parallel to the interface, the critical
      temperature increases, while for a field applied perpendicular to the interface,
      it decreases. The effects of the field on surface tension and interfacial width
      are also investigated. For zero field, dipoles near the liquid-vapor interface
      show a weak orientation parallel to the interface. For fields parallel to the
      interface, ordering in the liquid phase is greater than the vapor, while for
      fields perpendicular to the interface, the opposite is true. 

PMID- 25768508
TI  - Rotational dynamics of simple asymmetric molecules.
AB  - Molecular dynamic simulations were carried out on rigid diatomic molecules, which
      exhibit both alpha (structural) and beta (secondary) dynamics. The relaxation
      scenarios range from onset behavior, in which a distinct alpha process emerges on
      cooling, to merging behavior, associated with two relaxation peaks that converge
      at higher temperature. These properties, as well as the manifestation of the beta
      peak as an excess wing, depend not only on thermodynamic conditions, but also on
      both the symmetry of the molecule and the correlation function (odd or even) used
      to analyze its dynamics. These observations help to reconcile divergent results
      obtained from different experiments. For example, the beta process is more
      intense and the alpha-relaxation peak is narrower in dielectric relaxation
      spectra than in dynamic light scattering or NMR measurements. In the simulations
      herein, this follows from the weaker contribution of the secondary relaxation to
      even-order correlation functions, related to the magnitude of the relevant
      angular jumps. 

PMID- 25768509
TI  - Formation and liquid permeability of dense colloidal cube packings.
AB  - The liquid permeability of dense random packings of cubic colloids with rounded
      corners is studied for solid hematite cubes and hollow microporous silica cubes.
      The permeabilities of these two types of packings are similar, confirming that
      the micropores in the silica shell of the hollow cubes do not contribute to the
      permeability. From the Brinkman screening length ?k of ~16 nm, we infer that the
      relevant pores are indeed intercube pores. Furthermore, we relate the
      permeability to the volume fraction and specific solid volume of the cubes using
      the Kozeny-Carman relation. The Kozeny-Carman relation contains a constant that
      accounts for the topology and size distribution of the pores in the medium. The
      constant obtained from our study with aspherical particles is of the same order
      of magnitude as those from studies with spherical and ellipsoidal particles,
      which supports the notion that the Kozeny-Carman relation is applicable for any
      dense particle packing with (statistically) isotropic microstructures,
      irrespective of the particle shape.

PMID- 25768510
TI  - Quantum effects in the dynamics of deeply supercooled water.
AB  - Despite its simple chemical structure, water remains one of the most puzzling
      liquids with many anomalies at low temperatures. Combining neutron scattering and
      dielectric relaxation spectroscopy, we show that quantum fluctuations are not
      negligible in deeply supercooled water. Our dielectric measurements reveal the
      anomalously weak temperature dependence of structural relaxation in vapor
      deposited water close to the glass transition temperature T(g)~136K. We
      demonstrate that this anomalous behavior can be explained well by quantum
      effects. These results have significant implications for our understanding of
      water dynamics.

PMID- 25768511
TI  - Transport and diffusion properties of interacting colloidal particles in two
      dimensional microchannels with a periodic potential.
AB  - We report a Brownian dynamics simulation study of a two-dimensional system of
      repulsive colloidal particles in a channel geometry with a sinusoidal substrate
      potential under influence of a constant driving. The effect of this driving on
      the structure, mobility, and diffusion is discussed as well as the appearance of
      kink and antikink solitons. The competing order principles of the hexagonal
      crystal structure, the period of the substrate, and the layering due to the
      confining walls can be either commensurable or incommensurable. The combination
      of those three leads to new effects. The simultaneous occurrence of kinks and
      antikinks can be observed, due to the energy difference between boundary- and
      midlanes, and similarities to the electron-hole conductivity in a semiconductor
      can be found. 

PMID- 25768512
TI  - Atomistic mechanisms of intermittent plasticity in metals: dislocation avalanches
      and defect cluster pinning.
AB  - Intermittent plastic deformation in crystals with power-law behaviors has been
      reported in previous experimental studies. The power-law behavior is reminiscent
      of self-organized criticality, and mesoscopic models have been proposed that
      describe this behavior in crystals. In this paper, we show that intermittent
      plasticity in metals under tensile deformation can be observed in molecular
      dynamics models, using embedded atom method potentials for Ni, Cu, and Al. Power
      law behaviors of stress drop and waiting time of plastic deformation events are
      observed. It is shown that power-law behavior is due to dislocation avalanche
      motions in Cu and Ni. A different mechanism of dislocation pinning is found in
      Al. These different stress relaxation mechanisms give different power-law
      exponents. We propose a probabilistic model to describe the novel dislocation
      motion in Al and analytically deduce the power-law behavior. 

PMID- 25768513
TI  - Mesoscopic nucleation theory for confined systems: a one-parameter model.
AB  - Classical nucleation theory has been recently reformulated based on fluctuating
      hydrodynamics [J. F. Lutsko and M. A. Duran-Olivencia, Classical nucleation
      theory from a dynamical approach to nucleation, J. Chem. Phys. 138, 244908
      (2013). The present work extends this effort to the case of nucleation in
      confined systems such as small pores and vesicles. The finite available mass
      imposes a maximal supercritical cluster size and prohibits nucleation altogether
      if the system is too small. We quantity the effect of system size on the
      nucleation rate. We also discuss the effect of relaxing the capillary-model
      assumption of zero interfacial width resulting in significant changes in the
      nucleation barrier and nucleation rate.

PMID- 25768514
TI  - Formation and arrangement of pits by a corrosive gas.
AB  - When corroding or otherwise aggressive particles are incident on a surface, pits
      can form. For example, under certain circumstances rock surfaces that are exposed
      to salts can form regular tessellating patterns of pits known as "tafoni." We
      introduce a simple lattice model in which a gas of corrosive particles, described
      by a discrete, biased diffusion equation, drifts onto a surface. Each gas
      particle has a fixed probability of being absorbed and causing damage at each
      contact. The surface is represented by a lattice of strength numbers which reduce
      after each absorbtion event, with sites being removed when their strength becomes
      negative. Regular formations of pits arise spontaneously, with each pit having a
      characteristic trapezoidal geometry determined by the particle bias, absorbtion
      probability, and surface strength. The formation of this geometry may be
      understood in terms of a first order partial differential equation and is a
      consequence of particle concentration gradients which arise in the pits. By
      viewing pits as particle funnels, we are able to relate the gradient of pit walls
      to absorbtion probability and particle bias. 

PMID- 25768515
TI  - Confined disclinations: exterior versus material constraints in developable thin
      elastic sheets.
AB  - We examine the shape change of a thin disk with an inserted wedge of material
      when it is pushed against a plane, using analytical, numerical, and experimental
      methods. Such sheets occur in packaging, surgery, and nanotechnology. We
      approximate the sheet as having vanishing strain, so that it takes a conical form
      in which straight generators converge to a disclination singularity. Then, its
      shape is that which minimizes elastic bending energy alone. Real sheets are
      expected to approach this limiting shape as their thickness approaches zero. The
      planar constraint forces a sector of the sheet to buckle into the third
      dimension. We find that the unbuckled sector is precisely semicircular,
      independent of the angle delta of the inserted wedge. We generalize the analysis
      to include conical as well as planar constraints and thereby establish a law of
      corresponding states for shallow cones of slope epsilon and thin wedges. In this
      regime, the single parameter delta/epsilon^{2} determines the shape. We discuss
      the singular limit in which the cone becomes a plane, and the unexpected slow
      convergence to the semicircular buckling observed in real sheets. 

PMID- 25768516
TI  - Localized microjetting in the collapse of surface macrocavities.
AB  - This paper focuses on the multiscale mechanism of collapse of hemicylindrical
      annular surface macrocavities in steel caused by high-strain, high-strain rate
      plastic flow of copper. Experiments and simulations revealed that a two-stage
      process is responsible for the observed microjetting phenomena: the formation of
      lateral copper microjets from the localized shear flow in copper at the interface
      during the filling of the cavity, and their subsequent collision at the apex of
      the macrocavity generating two additional horizontal microjets. The lengths of
      these microjets were an order of magnitude smaller than the cavity size but
      linearly scaled with the cavity radius. This process of microjet development is
      sensitive to the cavity geometry and is unlike the previously observed jetting
      phenomena in cavitation, impact crater collapse, or shock-induced cavity
      collapse. 

PMID- 25768517
TI  - Implications of interface conventions for morphometric thermodynamics.
AB  - Several model fluids in contact with planar, spherical, and cylindrical walls are
      investigated for small number densities within density functional theory. The
      dependence of the solid-fluid interfacial tension on the curvature of spherical
      and cylindrical walls is examined and compared with the corresponding expression
      derived within the framework of morphometric thermodynamics. Particular attention
      is paid to the implications of the choice of the interface location, which
      underlies the definition of the interfacial tension. We find that morphometric
      thermodynamics is never exact for the considered systems and that its quality as
      an approximation depends sensitively on the choice of the interface location. 

PMID- 25768518
TI  - Interphase anisotropy effects on lamellar eutectics: a numerical study.
AB  - In directional solidification of binary eutectics, it is often observed that two
      phase lamellar growth patterns grow tilted with respect to the direction z of the
      imposed temperature gradient. This crystallographic effect depends on the
      orientation of the two crystal phases alpha and beta with respect to z. Recently,
      an approximate theory was formulated that predicts the lamellar tilt angle as a
      function of the anisotropy of the free energy of the solid(alpha)-solid(beta)
      interphase boundary. We use two different numerical methods-phase field (PF) and
      dynamic boundary integral (BI)-to simulate the growth of steady periodic patterns
      in two dimensions as a function of the angle theta(R) between z and a reference
      crystallographic axis for a fixed relative orientation of alpha and beta
      crystals, that is, for a given anisotropy function (Wulff plot) of the interphase
      boundary. For Wulff plots without unstable interphase-boundary orientations, the
      two simulation methods are in excellent agreement with each other and confirm the
      general validity of the previously proposed theory. In addition, a
      crystallographic "locking" of the lamellae onto a facet plane is well reproduced
      in the simulations. When unstable orientations are present in the Wulff plot, it
      is expected that two distinct values of the tilt angle can appear for the same
      crystal orientation over a finite theta(R) range. This bistable behavior, which
      has been observed experimentally, is well reproduced by BI simulations but not by
      the PF model. Possible reasons for this discrepancy are discussed.

PMID- 25768519
TI  - Molecular organization of nematic liquid crystals between concentric cylinders:
      role of the elastic anisotropy.
AB  - The orientational order in a nematic liquid crystal sample confined to an annular
      region between two concentric cylinders is investigated by means of lattice Monte
      Carlo simulations. Strong anchoring and homeotropic orientations, parallel to the
      radial direction, are implemented at the confining surfaces. The elastic
      anisotropy is taken into account in the bulk interactions by using the pair
      potential introduced by Gruhn and Hess [T. Gruhn and S. Hess, Z. Naturforsch. A
      51, 1 (1996)] and parametrized by Romano and Luckhurst [S. Romano, Int. J. Mod.
      Phys. B 12, 2305 (1998); Phys. Lett. A 302, 203 (2002); G. R. Luckhurst and S.
      Romano, Liq. Cryst. 26, 871 (1999)], i.e., the so-called GHRL potential. In the
      case of equal elastic constants, a small but appreciable deformation along the
      cylinder axis direction is observed, whereas when the values of K(11)/K(33) if
      K(22)=K(33) are low enough, all the spins in the bulk follow the orientation
      imposed by the surfaces. For larger values of K(11)/K(33), spontaneous
      deformations, perpendicular to the polar plane, increase significantly. Our
      findings indicate that the onset of these deformations also depends on the ratio
      K(22)/K(33) and on the radius of the cylindrical surfaces. Although expected from
      the elastic theory, no tangential component of the deformations was observed in
      the simulations for the set of parameters analyzed.

PMID- 25768520
TI  - Polarization-stiffened ferroelectric liquid crystals: a thickness-independent
      bistable switching voltage with a lower limit of about 2 V and the transition to
      thresholdless switching.
AB  - Typical ferroelectric Sm-C(*) liquid crystal (FLC) cells exhibit a voltage
      threshold for switching from one stable state to another despite the FLC's
      response being inherently continuous and thresholdless (free rotation of the
      director around the tilt cone). This switching threshold is due to FLC-surface
      interactions and to the chevron smectic structure commonly formed in cells. It is
      shown here that the FLC electrostatic energy contribution ~P(S)(2) responsible
      for thresholdless switching of high-P(S) FLCs also plays a key role in the
      bistable switching of lower-P(S) FLCs. Among the consequences are that it can be
      difficult to lower a cell's threshold below V(TB)~3.4(B/E(F))(1/2) (B and E(F)
      are the FLC's elastic and dielectric constants), that a cell's threshold becomes
      independent of cell thickness once it substantially exceeds the characteristic
      length xi(P)=(E(F)B)(1/2)/P(S), and that there are conditions under which
      alignment layer capacitance can decrease rather than increase the threshold
      (i.e., transition to thresholdless switching). A model that predicts and explains
      these behaviors is presented along with threshold measurements of representative
      FLC cells.

PMID- 25768521
TI  - Anisotropy of the electro-optic Kerr effect in polymer-stabilized blue phases.
AB  - Liquid crystalline polymer stabilized blue phases (PSBPs) are candidate materials
      for next generation electro-optic switching devices because they form a self
      organized three-dimensional periodic structure and exhibit a fast response time
      of submillisecond order. Considering the crystallographic structures of PSBPs, it
      is intuitive to believe that the electro-optic effect would depend on the
      direction of the applied electric field; however, this relationship has not yet
      been investigated. In this study, we prepared two kinds of samples in which the
      (110) and (200) planes were oriented parallel to the substrates, and investigated
      the electro-optic Kerr effect as a field was applied between the two substrates.
      The two samples exhibited differing behaviors, with the Kerr coefficient of the
      (110)-oriented sample being larger by 20% than that of the (200)-oriented sample.
      These results imply that the electro-optic Kerr effect of PSBPs is not isotropic
      but anisotropic, just like cubic optical crystals. 

PMID- 25768522
TI  - Using a Peclet number for the translocation of a polymer through a nanopore to
      tune coarse-grained simulations to experimental conditions.
AB  - Coarse-grained simulations are often employed to study the translocation of DNA
      through a nanopore. The majority of these studies investigate the translocation
      process in a relatively generic sense and do not endeavor to match any particular
      set of experimental conditions. In this manuscript, we use the concept of a
      Peclet number for translocation, P(t), to compare the drift-diffusion balance in
      a typical experiment vs a typical simulation. We find that the standard coarse
      grained approach overestimates diffusion effects by anywhere from a factor of 5
      to 50 compared to experimental conditions using double stranded DNA (dsDNA). By
      defining a Peclet control parameter, lambda, we are able to correct this and tune
      the simulations to replicate the experimental P(t) (for dsDNA and other
      scenarios). To show the effect that a particular P(t) can have on the dynamics of
      translocation, we perform simulations across a wide range of P(t) values for two
      different types of driving forces: a force applied in the pore and a pulling
      force applied to the end of the polymer. As P(t) brings the system from a
      diffusion dominated to a drift dominated regime, a variety of effects are
      observed including a non-monotonic dependence of the translocation time tau on
      P(t) and a steep rise in the probability of translocating. Comparing the two
      force cases illustrates the impact of the crowding effects that occur on the
      trans side: a non-monotonic dependence of the width of the tau distributions is
      obtained for the in-pore force but not for the pulling force.

PMID- 25768523
TI  - Structuring of polymer solutions upon solvent evaporation.
AB  - The morphology of solution-cast, phase-separated polymers becomes finer with
      increasing solvent evaporation rate. We address this observation theoretically
      for a model polymer where demixing is induced by steady solvent evaporation. In
      contrast to what is the case for a classical, thermal quench involving immiscible
      blends, the spinodal instability initially develops slowly and the associated
      length scale is not time invariant but decreases with time as t(-1/2). After a
      time lag, phase separation accelerates. Time lag and characteristic length
      exhibit power-law behavior as a function of the evaporation rate with exponents
      of -2/3 and -1/6. Interestingly, at later stages the spinodal structure
      disappears completely while a second length scale develops. The associated
      structure coarsens but does not follow the usual Lifshitz-Slyozov-Wagner
      kinetics.

PMID- 25768524
TI  - Atomistic study of macroscopic analogs to short-chain molecules.
AB  - We use a bath of chaotic surface waves in water to mechanically and
      macroscopically mimic the thermal behavior of a short articulated chain with only
      nearest-neighbor interactions. The chaotic waves provide isotropic and random
      agitation to which a temperature can be ascribed, allowing the chain to passively
      explore its degrees of freedom in analogy to thermal motion. We track the chain
      in real time and infer end-to-end potentials using Boltzmann statistics. We
      extrapolate our results, by using Monte Carlo simulations of self-avoiding
      polymers, to lengths not accessible in our system. In the long-chain limit we
      demonstrate universal scaling of the statistical parameters of all chains in
      agreement with well-known predictions for self-avoiding walks. However, we find
      that the behavior of chains below a characteristic length scale fundamentally
      differs. We find that short chains have much greater compressional stiffness than
      would be expected. However, chains rapidly soften as length increases to meet
      with expected scalings. 

PMID- 25768525
TI  - External forces influence the elastic coupling effects during cargo transport by
      molecular motors.
AB  - Cellular transport is achieved by the cooperative action of molecular motors
      which are elastically linked to a common cargo. When the motors pull on the cargo
      at the same time, they experience fluctuating elastic strain forces induced by
      the stepping of the other motors. These elastic coupling forces can influence the
      motors' stepping and unbinding behavior and thereby the ability to transport
      cargos. Based on a generic single motor description, we introduce a framework
      that explains the response of two identical molecular motors to a constant
      external force. In particular, we relate the single motor parameters, the
      coupling strength and the external load force to the dynamics of the motor pair.
      We derive four distinct transport regimes and determine how the crossover lines
      between the regimes depend on the load force. Our description of the overall
      cargo dynamics takes into account relaxational displacements of the cargo caused
      by the unbinding of one motor. For large forces and weak elastic coupling these
      back-shifts dominate the displacements. To develop an intuitive understanding
      about motor cooperativity during cargo transport, we introduce a time scale for
      load sharing. This time scale allows us to predict how the regulation of single
      motor parameters influences the cooperativity. As an example, we show that up
      regulating the single motor processivity enhances load sharing of the motor pair.

PMID- 25768526
TI  - Effective reaction rates in diffusion-limited phosphorylation-dephosphorylation
      cycles.
AB  - We investigate the kinetics of the ubiquitous phosphorylation-dephosphorylation
      cycle on biological membranes by means of kinetic Monte Carlo simulations on the
      triangular lattice. We establish the dependence of effective macroscopic reaction
      rate coefficients as well as the steady-state phosphorylated substrate fraction
      on the diffusion coefficient and concentrations of opposing enzymes: kinases and
      phosphatases. In the limits of zero and infinite diffusion, the numerical results
      agree with analytical predictions; these two limits give the lower and the upper
      bound for the macroscopic rate coefficients, respectively. In the zero-diffusion
      limit, which is important in the analysis of dense systems, phosphorylation and
      dephosphorylation reactions can convert only these substrates which remain in
      contact with opposing enzymes. In the most studied regime of nonzero but small
      diffusion, a contribution linearly proportional to the diffusion coefficient
      appears in the reaction rate. In this regime, the presence of opposing enzymes
      creates inhomogeneities in the (de)phosphorylated substrate distributions: The
      spatial correlation function shows that enzymes are surrounded by clouds of
      converted substrates. This effect becomes important at low enzyme concentrations,
      substantially lowering effective reaction rates. Effective reaction rates
      decrease with decreasing diffusion and this dependence is more pronounced for the
      less-abundant enzyme. Consequently, the steady-state fraction of phosphorylated
      substrates can increase or decrease with diffusion, depending on relative
      concentrations of both enzymes. Additionally, steady states are controlled by
      molecular crowders which, mostly by lowering the effective diffusion of
      reactants, favor the more abundant enzyme. 

PMID- 25768527
TI  - Cardiac contraction induces discordant alternans and localized block.
AB  - In this paper we use a simplified model of cardiac excitation-contraction
      coupling to study the effect of tissue deformation on the dynamics of alternans,
      i.e., alternations in the duration of the cardiac action potential, that occur at
      fast pacing rates and are known to be proarrhythmic. We show that small stretch
      activated currents can produce large effects and cause a transition from in-phase
      to off-phase alternations (i.e., from concordant to discordant alternans) and to
      conduction blocks. We demonstrate numerically and analytically that this effect
      is the result of a generic change in the slope of the conduction velocity
      restitution curve due to electromechanical coupling. Thus, excitation-contraction
      coupling can potentially play a relevant role in the transition to reentry and
      fibrillation. 

PMID- 25768528
TI  - Aggregation-fragmentation model of robust concentration gradient formation.
AB  - Concentration gradients of signaling molecules are essential for patterning
      during development and they have been observed in both unicellular and
      multicellular systems. In subcellular systems, clustering of the signaling
      molecule has been observed. We develop a theoretical model of cluster-mediated
      concentration gradient formation based on the Becker-Doring equations of
      aggregation-fragmentation processes. We show that such a mechanism produces
      robust concentration gradients on realistic time and spatial scales so long as
      the process of clustering does not significantly stabilize the signaling
      molecule. Finally, we demonstrate that such a model is applicable to the pom1p
      subcellular gradient in fission yeast. 

PMID- 25768529
TI  - Reproducible radiation-damage processes in proteins irradiated by intense x-ray
      pulses.
AB  - X-ray free-electron lasers have enabled femtosecond protein nanocrystallography,
      a novel method to determine the structure of proteins. It allows time-resolved
      imaging of nanocrystals that are too small for conventional crystallography. The
      short pulse duration helps in overcoming the detrimental effects of radiation
      damage because x rays are scattered before the sample has been significantly
      altered. It has been suggested that, fortuitously, the diffraction process self
      terminates abruptly once radiation damage destroys the crystalline order. Our
      calculations show that high-intensity x-ray pulses indeed trigger a cascade of
      damage processes in ferredoxin crystals, a particular metalloprotein of interest.
      However, we found that the damage process is initially not completely random.
      Correlations exist among the protein monomers, so that Bragg diffraction still
      occurs in the damaged crystals, despite significant atomic displacements. Our
      results show that the damage process is reproducible to a certain degree, which
      is potentially beneficial for the orientation step in single-molecule imaging. 

PMID- 25768530
TI  - Vibronically coherent speed-up of the excitation energy transfer in the Fenna
      Matthews-Olson complex.
AB  - We show that underdamped molecular vibrations fuel the efficient excitation
      energy transfer in the Fenna-Matthews-Olson molecular aggregate under realistic
      physiological conditions. By employing an environmental fluctuation spectral
      function derived from experiments, we obtain numerically exact results for the
      exciton quantum dynamics in the presence of underdamped vibrationally coherent
      quantum states. Assuming the prominent 180-cm(-1) vibrational mode to be
      underdamped, additional coherent transport channels for the excitation energy
      transfer open up and we observe an increase of the transfer speed towards the
      reaction center by up to 24%.

PMID- 25768531
TI  - Theoretical analysis of discreteness-induced transition in autocatalytic reaction
      dynamics.
AB  - Transitions in the qualitative behavior of chemical reaction dynamics with a
      decrease in molecule number have attracted much attention. Here, a method based
      on a Markov process with a tridiagonal transition matrix is applied to the
      analysis of this transition in reaction dynamics. The transition to bistability
      due to the small-number effect and the mean switching time between the bistable
      states are analytically calculated in agreement with numerical simulations. In
      addition, a novel transition involving the reversal of the chemical reaction flow
      is found in the model under an external flow, and also in a three-component
      model. The generality of this transition and its correspondence to biological
      phenomena are also discussed. 

PMID- 25768532
TI  - Protein unfolding from free-energy calculations: integration of the Gaussian
      network model with bond binding energies.
AB  - Motivated by single molecule experiments, we study thermal unfolding pathways of
      four proteins, chymotrypsin inhibitor, barnase, ubiquitin, and adenylate kinase,
      using bond network models that combine bond energies and elasticity. The protein
      elasticity is described by the Gaussian network model (GNM), to which we add
      prescribed bond binding energies that are assigned to all (nonbackbone)
      connecting bonds in the GNM of native state and assumed identical for simplicity.
      Using exact calculation of the Helmholtz free energy for this model, we consider
      bond rupture single events. The bond designated for rupture is chosen by
      minimizing the free-energy difference for the process, over all (nonbackbone)
      bonds in the network. Plotting the free-energy profile along this pathway at
      different temperatures, we observe a few major partial unfolding, metastable or
      stable, states, that are separated by free-energy barriers and change role as the
      temperature is raised. In particular, for adenylate kinase we find three major
      partial unfolding states, which is consistent with single molecule FRET
      experiments [Pirchi et al., Nat. Commun. 2, 493 (2011)] for which hidden Markov
      analysis reveals between three and five such states. Such states can play a major
      role in enzymatic activity.

PMID- 25768533
TI  - Effective rates from thermodynamically consistent coarse-graining of models for
      molecular motors with probe particles.
AB  - Many single-molecule experiments for molecular motors comprise not only the motor
      but also large probe particles coupled to it. The theoretical analysis of these
      assays, however, often takes into account only the degrees of freedom
      representing the motor. We present a coarse-graining method that maps a model
      comprising two coupled degrees of freedom which represent motor and probe
      particle to such an effective one-particle model by eliminating the dynamics of
      the probe particle in a thermodynamically and dynamically consistent way. The
      coarse-grained rates obey a local detailed balance condition and reproduce the
      net currents. Moreover, the average entropy production as well as the
      thermodynamic efficiency is invariant under this coarse-graining procedure. Our
      analysis reveals that only by assuming unrealistically fast probe particles, the
      coarse-grained transition rates coincide with the transition rates of the
      traditionally used one-particle motor models. Additionally, we find that for
      multicyclic motors the stall force can depend on the probe size. We apply this
      coarse-graining method to specific case studies of the F(1)-ATPase and the
      kinesin motor.

PMID- 25768534
TI  - Differential growth of wrinkled biofilms.
AB  - Biofilms are antibiotic-resistant bacterial aggregates that grow on moist
      surfaces and can trigger hospital-acquired infections. They provide a classical
      example in biology where the dynamics of cellular communities may be observed and
      studied. Gene expression regulates cell division and differentiation, which
      affect the biofilm architecture. Mechanical and chemical processes shape the
      resulting structure. We gain insight into the interplay between cellular and
      mechanical processes during biofilm development on air-agar interfaces by means
      of a hybrid model. Cellular behavior is governed by stochastic rules informed by
      a cascade of concentration fields for nutrients, waste, and autoinducers.
      Cellular differentiation and death alter the structure and the mechanical
      properties of the biofilm, which is deformed according to Foppl-Von Karman
      equations informed by cellular processes and the interaction with the substratum.
      Stiffness gradients due to growth and swelling produce wrinkle branching. We are
      able to reproduce wrinkled structures often formed by biofilms on air-agar
      interfaces, as well as spatial distributions of differentiated cells commonly
      observed with B. subtilis. 

PMID- 25768535
TI  - Competition between surface adsorption and folding of fibril-forming
      polypeptides.
AB  - Self-assembly of polypeptides into fibrillar structures can be initiated by
      planar surfaces that interact favorably with certain residues. Using a coarse
      grained model, we systematically studied the folding and adsorption behavior of a
      beta-roll forming polypeptide. We find that there are two different folding
      pathways depending on the temperature: (i) at low temperature, the polypeptide
      folds in solution into a beta-roll before adsorbing onto the attractive surface;
      (ii) at higher temperature, the polypeptide first adsorbs in a disordered state
      and folds while on the surface. The folding temperature increases with increasing
      attraction as the folded beta-roll is stabilized by the surface. Surprisingly,
      further increasing the attraction lowers the folding temperature again, as strong
      attraction also stabilizes the adsorbed disordered state, which competes with
      folding of the polypeptide. Our results suggest that to enhance the folding, one
      should use a weakly attractive surface. They also explain the recent experimental
      observation of the nonmonotonic effect of charge on the fibril formation on an
      oppositely charged surface [C. Charbonneau et al., ACS Nano 8, 2328 (2014)].

PMID- 25768536
TI  - Effects of extracellular potassium diffusion on electrically coupled neuron
      networks.
AB  - Potassium accumulation and diffusion during neuronal epileptiform activity have
      been observed experimentally, and potassium lateral diffusion has been suggested
      to play an important role in nonsynaptic neuron networks. We adopt a hippocampal
      CA1 pyramidal neuron network in a zero-calcium condition to better understand the
      influence of extracellular potassium dynamics on the stimulus-induced activity.
      The potassium concentration in the interstitial space for each neuron is
      regulated by potassium currents, Na(+)-K(+) pumps, glial buffering, and ion
      diffusion. In addition to potassium diffusion, nearby neurons are also coupled
      through gap junctions. Our results reveal that the latency of the first spike
      responding to stimulus monotonically decreases with increasing gap-junction
      conductance but is insensitive to potassium diffusive coupling. The duration of
      network oscillations shows a bell-like shape with increasing potassium diffusive
      coupling at weak gap-junction coupling. For modest electrical coupling, there is
      an optimal K(+) diffusion strength, at which the flow of potassium ions among the
      network neurons appropriately modulates interstitial potassium concentrations in
      a degree that provides the most favorable environment for the generation and
      continuance of the action potential waves in the network.

PMID- 25768537
TI  - Line tension of multicomponent bilayer membranes.
AB  - The line tension or edge energy of bilayer membranes self-assembled from binary
      amphiphilic molecules is studied using self-consistent-field theory (SCFT).
      Specifically, solutions of the SCFT equations corresponding to an infinite
      membrane with a circular pore, or an open membrane, are obtained for a coarse
      grained model in which the amphiphilic species and hydrophilic solvents are
      represented by ABandED diblock copolymers and C homopolymers, respectively. The
      edge energy of the membrane is extracted from the free energy of the open
      membranes. Results for membranes composed of mixtures of symmetric and cone- or
      inverse cone-shaped amphiphilic molecules with neutral and/or repulsive
      interactions are obtained and analyzed. It is observed that an increase in the
      concentration of the cone-shaped species leads to a decrease of the line tension.
      In contrast, adding inverse cone-shaped copolymers results in an increase of the
      line tension. Furthermore, the density profile of the copolymers reveals that the
      line tension is regulated by the distribution of the amphiphiles at the bilayer
      edge. 

PMID- 25768538
TI  - Photoactivated biological processes as quantum measurements.
AB  - We outline a framework for describing photoactivated biological reactions as
      generalized quantum measurements of external fields, for which the biological
      system takes on the role of a quantum meter. By using general arguments regarding
      the Hamiltonian that describes the measurement interaction, we identify the cases
      where it is essential for a complex chemical or biological system to exhibit
      nonequilibrium quantum coherent dynamics in order to achieve the requisite
      functionality. We illustrate the analysis by considering measurement of the solar
      radiation field in photosynthesis and measurement of the earth's magnetic field
      in avian magnetoreception. 

PMID- 25768539
TI  - Charge regulation in ionic solutions: thermal fluctuations and Kirkwood-Schumaker
      interactions.
AB  - We study the behavior of two macroions with dissociable charge groups, regulated
      by local variables such as pH and electrostatic potential, immersed in a
      monovalent salt solution, considering cases where the net charge can either
      change sign or remain of the same sign depending on these local parameters. The
      charge regulation in both cases is described by the proper free-energy function
      for each of the macroions, while the coupling between the charges is evaluated on
      the approximate Debye-Huckel level. The charge correlation functions and the
      ensuing charge fluctuation forces are calculated analytically and numerically.
      Strong attraction between like-charged macroions is found close to the point of
      zero charge, specifically due to asymmetric, anticorrelated charge fluctuations
      of the macroion charges. The general theory is then implemented for a system of
      two proteinlike macroions, generalizing the form and magnitude of the Kirkwood
      Schumaker interaction. 

PMID- 25768540
TI  - Influence of ibuprofen on phospholipid membranes.
AB  - A basic understanding of biological membranes is of paramount importance as these
      membranes comprise the very building blocks of life itself. Cells depend in their
      function on a range of properties of the membrane, which are important for the
      stability and function of the cell, information and nutrient transport, waste
      disposal, and finally the admission of drugs into the cell and also the
      deflection of bacteria and viruses. We have investigated the influence of
      ibuprofen on the structure and dynamics of L-alpha-phosphatidylcholine (SoyPC)
      membranes by means of grazing incidence small-angle neutron scattering, neutron
      reflectometry, and grazing incidence neutron spin echo spectroscopy. From the
      results of these experiments, we were able to determine that ibuprofen induces a
      two-step structuring behavior in the SoyPC films, where the structure evolves
      from the purely lamellar phase for pure SoyPC over a superposition of two
      hexagonal phases to a purely hexagonal phase at high concentrations. A
      relaxation, which is visible when no ibuprofen is present in the membrane,
      vanishes upon addition of ibuprofen. This we attribute to a stiffening of the
      membrane. This behavior may be instrumental in explaining the toxic behavior of
      ibuprofen in long-term application. 

PMID- 25768541
TI  - Detachment, futile cycling, and nucleotide pocket collapse in myosin-V stepping.
AB  - Myosin-V is a highly processive dimeric protein that walks with 36-nm steps along
      actin tracks, powered by coordinated adenosine triphosphate (ATP) hydrolysis
      reactions in the two myosin heads. No previous theoretical models of the myosin-V
      walk reproduce all the observed trends of velocity and run length with adenosine
      diphosphate (ADP), ATP and external forcing. In particular, a result that has
      eluded all theoretical studies based upon rigorous physical chemistry is that run
      length decreases with both increasing [ADP] and [ATP]. We systematically analyze
      which mechanisms in existing models reproduce which experimental trends and use
      this information to guide the development of models that can reproduce them all.
      We formulate models as reaction networks between distinct mechanochemical states
      with energetically determined transition rates. For each network architecture, we
      compare predictions for velocity and run length to a subset of experimentally
      measured values, and fit unknown parameters using a bespoke Monte Carlo simulated
      annealing optimization routine. Finally we determine which experimental trends
      are replicated by the best-fit model for each architecture. Only two models
      capture them all: one involving [ADP]-dependent mechanical detachment, and
      another including [ADP]-dependent futile cycling and nucleotide pocket collapse.
      Comparing model-predicted and experimentally observed kinetic transition rates
      favors the latter. 

PMID- 25768542
TI  - Statistics of a neuron model driven by asymmetric colored noise.
AB  - Irregular firing of neurons can be modeled as a stochastic process. Here we study
      the perfect integrate-and-fire neuron driven by dichotomous noise, a Markovian
      process that jumps between two states (i.e., possesses a non-Gaussian statistics)
      and exhibits nonvanishing temporal correlations (i.e., represents a colored
      noise). Specifically, we consider asymmetric dichotomous noise with two different
      transition rates. Using a first-passage-time formulation, we derive exact
      expressions for the probability density and the serial correlation coefficient of
      the interspike interval (time interval between two subsequent neural action
      potentials) and the power spectrum of the spike train. Furthermore, we extend the
      model by including additional Gaussian white noise, and we give approximations
      for the interspike interval (ISI) statistics in this case. Numerical simulations
      are used to validate the exact analytical results for pure dichotomous noise, and
      to test the approximations of the ISI statistics when Gaussian white noise is
      included. The results may help to understand how correlations and asymmetry of
      noise and signals in nerve cells shape neuronal firing statistics. 

PMID- 25768543
TI  - Modeling the electrical conduction in DNA nanowires: charge transfer and lattice
      fluctuation theories.
AB  - An analytical approach is proposed for the investigation of the conductivity
      properties of DNA. The charge mobility of DNA is studied based on an extended
      Peyrard-Bishop-Holstein model when the charge carrier is also subjected to an
      external electrical field. We have obtained the values of some of the system
      parameters, such as the electron-lattice coupling constant, by using the mean
      Lyapunov exponent method. On the other hand, the electrical current operator is
      calculated directly from the lattice operators. Also, we have studied Landauer
      resistance behavior with respect to the external field, which could serve as the
      interface between chaos theory tools and electronic concepts. We have examined
      the effect of two types of electrical fields (dc and ac) and variation of the
      field frequency on the current flowing through DNA. A study of the current
      voltage (I-V) characteristic diagram reveals regions with a (quasi-)Ohmic
      property and other regions with negative differential resistance (NDR). NDR is a
      phenomenon that has been observed experimentally in DNA at room temperature. We
      have tried to study the affected agents in charge transfer phenomena in DNA to
      better design nanostructures. 

PMID- 25768544
TI  - Polarization of cells and soft objects driven by mechanical interactions:
      consequences for migration and chemotaxis.
AB  - We study a generic model for the polarization and motility of self-propelled soft
      objects, biological cells, or biomimetic systems, interacting with a viscous
      substrate. The active forces generated by the cell on the substrate are modeled
      by means of oscillating force multipoles at the cell-substrate interface.
      Symmetry breaking and cell polarization for a range of cell sizes naturally
      "emerge" from long range mechanical interactions between oscillating units,
      mediated both by the intracellular medium and the substrate. However, the
      harnessing of cell polarization for motility requires substrate-mediated
      interactions. Motility can be optimized by adapting the oscillation frequency to
      the relaxation time of the system or when the substrate and cell viscosities
      match. Cellular noise can destroy mechanical coordination between force
      generating elements within the cell, resulting in sudden changes of polarization.
      The persistence of the cell's motion is found to depend on the cell size and the
      substrate viscosity. Within such a model, chemotactic guidance of cell motion is
      obtained by directionally modulating the persistence of motion, rather than by
      modulating the instantaneous cell velocity, in a way that resembles the run and
      tumble chemotaxis of bacteria. 

PMID- 25768545
TI  - Influence of organelle geometry on the apparent binding kinetics of peripheral
      membrane proteins.
AB  - Information processing in living cells frequently involves an exchange of
      peripheral membrane proteins between the cytosol and organelle membranes. The
      typical time scale tau of these association-dissociation cycles is commonly
      quantified in vivo via fluorescence recovery after photobleaching (FRAP).
      Contrary to common assumptions, we show here that tau values determined by FRAP
      depend on the size and number of target structures. Hence, FRAP times alone are
      insufficient to draw conclusions about the proteins' binding kinetics. In
      contrast, extracting primary molecular association and dissociation rates from
      FRAP approaches provides a size-independent and therefore robust measure for the
      proteins' binding kinetics. We support our theoretical considerations with
      experiments on the small GTPase Arf-1 that transiently associates with Golgi
      membranes: While Arf-1 recovery times in untreated cells and in cells with
      disrupted microtubules are significantly different, the molecular kinetic rates
      are shown to be the same in both cases. 

PMID- 25768546
TI  - Modeling spontaneous chiral symmetry breaking and deracemization phenomena:
      discrete versus continuum approaches.
AB  - We derive the class of population balance equations (PBE), recently applied to
      model the Viedma deracemization experiment, from an underlying microreversible
      kinetic reaction scheme. The continuum limit establishing the relationship
      between the micro- and macroscopic processes and the associated particle fluxes
      erases the microreversible nature of the molecular interactions in the population
      growth rate functions and limits the scope of such PBE models to strict kinetic
      control. The irreversible binary agglomeration processes modeled in those PBEs
      contribute an additional source of kinetic control. These limitations are crucial
      regarding the question of the origin of biological homochirality, where the
      interest in any model lies precisely in its ability for absolute asymmetric
      synthesis and the amplification of the tiny inherent statistical chiral
      fluctuations about the ideal racemic composition up to observable enantiometric
      excess levels. 

PMID- 25768547
TI  - Detrended fluctuation analysis as a regression framework: estimating dependence
      at different scales.
AB  - We propose a framework combining detrended fluctuation analysis with standard
      regression methodology. The method is built on detrended variances and
      covariances and it is designed to estimate regression parameters at different
      scales and under potential nonstationarity and power-law correlations. The former
      feature allows for distinguishing between effects for a pair of variables from
      different temporal perspectives. The latter ones make the method a significant
      improvement over the standard least squares estimation. Theoretical claims are
      supported by Monte Carlo simulations. The method is then applied on selected
      examples from physics, finance, environmental science, and epidemiology. For most
      of the studied cases, the relationship between variables of interest varies
      strongly across scales. 

PMID- 25768548
TI  - Anomalous scaling in an age-dependent branching model.
AB  - We introduce a one-parametric family of tree growth models, in which branching
      probabilities decrease with branch age tau as tau(-alpha). Depending on the
      exponent alpha, the scaling of tree depth with tree size n displays a transition
      between the logarithmic scaling of random trees and an algebraic growth. At the
      transition (alpha=1) tree depth grows as (logn)(2). This anomalous scaling is in
      good agreement with the trend observed in evolution of biological species, thus
      providing a theoretical support for age-dependent speciation and associating it
      to the occurrence of a critical point.

PMID- 25768549
TI  - Unambiguous reconstruction of network structure using avalanche dynamics.
AB  - A robust method for inferring the structure of networks is presented based on the
      one-to-one correspondence between the expected composition of cascades of bursts
      of activity, called crackling noise or avalanches, and the weight matrix. Using a
      model of neuronal avalanches as a paradigmatic example, we derive this
      correspondence exactly by calculating the closed-form expression of the joint
      probability distribution of avalanche sizes obtained by counting separately the
      number of elements active in each subnetwork during avalanches. 

PMID- 25768550
TI  - Sequential defense against random and intentional attacks in complex networks.
AB  - Network robustness against attacks is one of the most fundamental researches in
      network science as it is closely associated with the reliability and
      functionality of various networking paradigms. However, despite the study on
      intrinsic topological vulnerabilities to node removals, little is known on the
      network robustness when network defense mechanisms are implemented, especially
      for networked engineering systems equipped with detection capabilities. In this
      paper, a sequential defense mechanism is first proposed in complex networks for
      attack inference and vulnerability assessment, where the data fusion center
      sequentially infers the presence of an attack based on the binary attack status
      reported from the nodes in the network. The network robustness is evaluated in
      terms of the ability to identify the attack prior to network disruption under two
      major attack schemes, i.e., random and intentional attacks. We provide a
      parametric plug-in model for performance evaluation on the proposed mechanism and
      validate its effectiveness and reliability via canonical complex network models
      and real-world large-scale network topology. The results show that the sequential
      defense mechanism greatly improves the network robustness and mitigates the
      possibility of network disruption by acquiring limited attack status information
      from a small subset of nodes in the network. 

PMID- 25768551
TI  - Forest-fire model as a supercritical dynamic model in financial systems.
AB  - Recently large-scale cascading failures in complex systems have garnered
      substantial attention. Such extreme events have been treated as an integral part
      of self-organized criticality (SOC). Recent empirical work has suggested that
      some extreme events systematically deviate from the SOC paradigm, requiring a
      different theoretical framework. We shed additional theoretical light on this
      possibility by studying financial crisis. We build our model of financial crisis
      on the well-known forest fire model in scale-free networks. Our analysis shows a
      nontrivial scaling feature indicating supercritical behavior, which is
      independent of system size. Extreme events in the supercritical state result from
      bursting of a fat bubble, seeds of which are sown by a protracted period of a
      benign financial environment with few shocks. Our findings suggest that
      policymakers can control the magnitude of financial meltdowns by keeping the
      economy operating within reasonable duration of a benign environment. 

PMID- 25768552
TI  - Slow poisoning and destruction of networks: edge proximity and its implications
      for biological and infrastructure networks.
AB  - We propose a network metric, edge proximity, P(e), which demonstrates the
      importance of specific edges in a network, hitherto not captured by existing
      network metrics. The effects of removing edges with high P(e) might initially
      seem inconspicuous but are eventually shown to be very harmful for networks.
      Compared to existing strategies, the removal of edges by P(e) leads to a
      remarkable increase in the diameter and average shortest path length in
      undirected real and random networks till the first disconnection and well beyond.
      P(e) can be consistently used to rupture the network into two nearly equal parts,
      thus presenting a very potent strategy to greatly harm a network. Targeting by
      P(e) causes notable efficiency loss in U.S. and European power grid networks.
      P(e) identifies proteins with essential cellular functions in protein-protein
      interaction networks. It pinpoints regulatory neural connections and important
      portions of the neural and brain networks, respectively. Energy flow interactions
      identified by P(e) form the backbone of long food web chains. Finally, we
      scrutinize the potential of P(e) in edge controllability dynamics of directed
      networks.

PMID- 25768553
TI  - Flow and clogging of a sheep herd passing through a bottleneck.
AB  - We present an experimental study of a flock passing through a narrow door. Video
      monitoring of daily routines in a farm has enabled us to collect a sizable amount
      of data. By measuring the time lapse between the passage of consecutive animals,
      some features of the flow regime can be assessed. A quantitative definition of
      clogging is demonstrated based on the passage time statistics. These display
      broad tails, which can be fitted by power laws with a relatively large exponent.
      On the other hand, the distribution of burst sizes robustly evidences exponential
      behavior. Finally, borrowing concepts from granular physics and statistical
      mechanics, we evaluate the effect of increasing the door size and the performance
      of an obstacle placed in front of it. The success of these techniques opens new
      possibilities regarding their eventual extension to the management of human
      crowds. 

PMID- 25768554
TI  - Connectivity interplays with age in shaping contagion over networks with vital
      dynamics.
AB  - The effects of network topology on the emergence and persistence of infectious
      diseases have been broadly explored in recent years. However, the influence of
      the vital dynamics of the hosts (i.e., birth-death processes) on the network
      structure, and their effects on the pattern of epidemics, have received less
      attention in the scientific community. Here, we study Susceptible-Infected
      Recovered(-Susceptible) [SIR(S)] contact processes in standard networks (of Erdos
      Renyi and Barabasi-Albert type) that are subject to host demography. Accounting
      for the vital dynamics of hosts is far from trivial, and it causes the scale-free
      networks to lose their characteristic fat-tailed degree distribution. We
      introduce a broad class of models that integrate the birth and death of
      individuals (nodes) with the simplest mechanisms of infection and recovery, thus
      generating age-degree structured networks of hosts that interact in a complex
      manner. In our models, the epidemiological state of each individual may depend
      both on the number of contacts (which changes through time because of the birth
      death process) and on its age, paving the way for a possible age-dependent
      description of contagion and recovery processes. We study how the proportion of
      infected individuals scales with the number of contacts among them. Rather
      unexpectedly, we discover that the result of highly connected individuals at the
      highest risk of infection is not as general as commonly believed. In infections
      that confer permanent immunity to individuals of vital populations (SIR
      processes), the nodes that are most likely to be infected are those with
      intermediate degrees. Our age-degree structured models allow such findings to be
      deeply analyzed and interpreted, and they may aid in the development of effective
      prevention policies. 

PMID- 25768555
TI  - Self-organized correlations lead to explosive synchronization.
AB  - Very recently, a first-order phase transition, named explosive synchronization
      (ES), has attracted great attention due to its remarkable novelty in theory and
      significant impact in applications. However, so far, all observations of ES have
      been associated with various correlation constraints on system parameters, which
      restrict its generality and applications. Here we consider heterogeneous networks
      around Hopf bifurcation point described by chemical reaction-diffusion systems
      and also by their reduced order parameter versions, the complex Ginzburg-Landau
      equations, and demonstrate that explosive synchronization can appear as an
      emergent feature of oscillatory networks, and the restrictions on specific
      parameter correlations used so far for ES can be lifted entirely. Theoretical
      analyses and numerical simulations show with a perfect agreement that explosive
      synchronization can appear in networks with nodes having identical natural
      frequencies, and necessary correlation conditions for ES can be realized in a
      self-organized manner by network evolution. 

PMID- 25768556
TI  - Effect of zealotry in high-dimensional opinion dynamics models.
AB  - Most of the work on opinion dynamics models focuses on the case of two or three
      opinion types. We consider the case of an arbitrary number of opinions in the
      mean field case of the naming game model in which it is assumed the population is
      infinite and all individuals are neighbors. A particular challenge of the naming
      game model is that the number of variables, which corresponds to the number of
      possible sets of opinions, grows exponentially with the number of possible
      opinions. We present a method for generating mean field dynamical equations for
      the general case of k opinions. We calculate the steady states in two important
      special cases in arbitrarily high dimension: the case in which there exist
      zealots of only one type, and the case in which there are an equal number of
      zealots for each opinion. We show that in these special cases a phase transition
      occurs at critical values p(c) of the parameter p describing the fraction of
      zealots. In the former case, the critical value determines the threshold value
      beyond which it is not possible for the opinion with no zealots to be held by
      more nodes than the opinion with zealots, and this point remains fixed regardless
      of dimension. In the latter case, the critical point p(c) is the threshold value
      beyond which a stalemate between all k opinions is guaranteed, and we show that
      it decays precisely as a lognormal curve in k.

PMID- 25768557
TI  - Fault-induced delayed voltage recovery in a long inhomogeneous power-distribution
      feeder.
AB  - We analyze the dynamics of a distribution circuit loaded with many induction
      motors and subjected to sudden changes in voltage at the beginning of the
      circuit. As opposed to earlier work by Duclut et al. [Phys. Rev. E 87, 062802
      (2013)], the motors are disordered, i.e., the mechanical torque applied to the
      motors varies in a random manner along the circuit. In spite of the disorder,
      many of the qualitative features of a homogeneous circuit persist, e.g., long
      range motor-motor interactions mediated by circuit voltage and electrical power
      flows result in coexistence of the spatially extended and propagating normal and
      stalled phases. We also observed a new phenomenon absent in the case without
      inhomogeneity or disorder. Specifically, the transition front between the normal
      and stalled phases becomes somewhat random, even when the front is moving very
      slowly or is even stationary. Motors within the blurred domain appear in a normal
      or stalled state depending on the local configuration of the disorder. We
      quantify the effects of the disorder and discuss the statistics of distribution
      dynamics, e.g., the front position and width, total active and reactive
      consumption of the feeder, and maximum clearing time.

PMID- 25768558
TI  - Mean-field approximation for the Sznajd model in complex networks.
AB  - This paper studies the Sznajd model for opinion formation in a population
      connected through a general network. A master equation describing the time
      evolution of opinions is presented and solved in a mean-field approximation.
      Although quite simple, this approximation allows us to capture the most important
      features regarding the steady states of the model. When spontaneous opinion
      changes are included, a discontinuous transition from consensus to polarization
      can be found as the rate of spontaneous change is increased. In this case we show
      that a hybrid mean-field approach including interactions between second nearest
      neighbors is necessary to estimate correctly the critical point of the
      transition. The analytical prediction of the critical point is also compared with
      numerical simulations in a wide variety of networks, in particular Barabasi
      Albert networks, finding reasonable agreement despite the strong approximations
      involved. The same hybrid approach that made it possible to deal with second
      order neighbors could just as well be adapted to treat other problems such as
      epidemic spreading or predator-prey systems. 

PMID- 25768559
TI  - Efficient algorithm to compute mutually connected components in interdependent
      networks.
AB  - Mutually connected components (MCCs) play an important role as a measure of
      resilience in the study of interdependent networks. Despite their importance, an
      efficient algorithm to obtain the statistics of all MCCs during the removal of
      links has thus far been absent. Here, using a well-known fully dynamic graph
      algorithm, we propose an efficient algorithm to accomplish this task. We show
      that the time complexity of this algorithm is approximately O(N(1.2)) for random
      graphs, which is more efficient than O(N(2)) of the brute-force algorithm. We
      confirm the correctness of our algorithm by comparing the behavior of the order
      parameter as links are removed with existing results for three types of double
      layer multiplex networks. We anticipate that this algorithm will be used for
      simulations of large-size systems that have been previously inaccessible.

PMID- 25768560
TI  - Measuring graph similarity through continuous-time quantum walks and the quantum
      Jensen-Shannon divergence.
AB  - In this paper we propose a quantum algorithm to measure the similarity between a
      pair of unattributed graphs. We design an experiment where the two graphs are
      merged by establishing a complete set of connections between their nodes and the
      resulting structure is probed through the evolution of continuous-time quantum
      walks. In order to analyze the behavior of the walks without causing wave
      function collapse, we base our analysis on the recently introduced quantum Jensen
      Shannon divergence. In particular, we show that the divergence between the
      evolution of two suitably initialized quantum walks over this structure is
      maximum when the original pair of graphs is isomorphic. We also prove that under
      special conditions the divergence is minimum when the sets of eigenvalues of the
      Hamiltonians associated with the two original graphs have an empty intersection. 

PMID- 25768561
TI  - Critical noise of majority-vote model on complex networks.
AB  - The majority-vote model with noise is one of the simplest nonequilibrium
      statistical model that has been extensively studied in the context of complex
      networks. However, the relationship between the critical noise where the order
      disorder phase transition takes place and the topology of the underlying networks
      is still lacking. In this paper, we use the heterogeneous mean-field theory to
      derive the rate equation for governing the model's dynamics that can analytically
      determine the critical noise f(c) in the limit of infinite network size N
      >infinity. The result shows that f(c) depends on the ratio of <k> to <k(3/2)>,
      where <k> and <k(3/2)> are the average degree and the 3/2 order moment of degree
      distribution, respectively. Furthermore, we consider the finite-size effect where
      the stochastic fluctuation should be involved. To the end, we derive the Langevin
      equation and obtain the potential of the corresponding Fokker-Planck equation.
      This allows us to calculate the effective critical noise f(c)(N) at which the
      susceptibility is maximal in finite-size networks. We find that the f(c)-f(c)(N)
      decays with N in a power-law way and vanishes for N->infinity. All the
      theoretical results are confirmed by performing the extensive Monte Carlo
      simulations in random k-regular networks, Erdos-Renyi random networks, and scale
      free networks.

PMID- 25768562
TI  - Chimera states in time-varying complex networks.
AB  - Chimera states have been recently found in a variety of different coupling
      schemes and geometries. In most cases, the underlying coupling structure is
      considered to be static, while many realistic systems display significant
      temporal changes in the pattern of connectivity. In this work we investigate a
      time-varying network made of two coupled populations of Kuramoto oscillators,
      where the links between the two groups are considered to vary over time. As a
      main result we find that the network may support stable, breathing, and
      alternating chimera states. We also find that, when the rate of connectivity
      changes is fast, compared to the oscillator dynamics, the network may be
      described by a low-dimensional system of equations. Unlike in the static
      heterogeneous case, the onset of alternating chimera states is due to the
      presence of fluctuations, which may be induced either by the finite size of the
      network or by large switching times. 

PMID- 25768563
TI  - Explosive synchronization with partial degree-frequency correlation.
AB  - Networks of Kuramoto oscillators with a positive correlation between the
      oscillators frequencies and the degree of their corresponding vertices exhibit so
      called explosive synchronization behavior, which is now under intensive
      investigation. Here we study and discuss explosive synchronization in a situation
      that has not yet been considered, namely when only a part, typically a small
      part, of the vertices is subjected to a degree-frequency correlation. Our results
      show that in order to have explosive synchronization, it suffices to have degree
      frequency correlations only for the hubs, the vertices with the highest degrees.
      Moreover, we show that a partial degree-frequency correlation does not only
      promotes but also allows explosive synchronization to happen in networks for
      which a full degree-frequency correlation would not allow it. We perform a mean
      field analysis and our conclusions were corroborated by exhaustive numerical
      experiments for synthetic networks and also for the undirected and unweighed
      version of a typical benchmark biological network, namely the neural network of
      the worm Caenorhabditis elegans. The latter is an explicit example where partial
      degree-frequency correlation leads to explosive synchronization with hysteresis,
      in contrast with the fully correlated case, for which no explosive
      synchronization is observed. 

PMID- 25768564
TI  - Impact of a leader on cluster synchronization.
AB  - We study the mechanisms of frequency-synchronized cluster formation in coupled
      nonidentical oscillators and investigate the impact of presence of a leader on
      the cluster synchronization. We find that the introduction of a leader, a node
      having large parameter mismatch, induces a profound change in the cluster pattern
      as well as in the mechanism of the cluster formation. The emergence of a leader
      generates a transition from the driven to the mixed cluster state. The frequency
      mismatch turns out to be responsible for this transition. Additionally, for a
      chaotic evolution, the driven mechanism stands as a primary mechanism for the
      cluster formation, whereas for a periodic evolution the self-organization
      mechanism becomes equally responsible. 

PMID- 25768565
TI  - Front propagation in channels with spatially modulated cross section.
AB  - Propagation of traveling fronts in a three-dimensional channel with spatially
      varying cross section is reduced to an equivalent one-dimensional reaction
      diffusion-advection equation with boundary-induced advection term. Treating the
      advection term as a weak perturbation, an equation of motion for the front
      position is derived. We analyze channels whose cross sections vary periodically
      with L along the propagation direction of the front. Taking the Schlogl model as
      a representative example, we calculate analytically the nonlinear dependence of
      the front velocity on the ratio L/l where l denotes the intrinsic front width. In
      agreement with finite-element simulations of the three-dimensional reaction
      diffusion dynamics, our theoretical results predicts boundary-induced propagation
      failure for a finite range of L/l values. In particular, the existence of the
      upper bound of L/l can be completely understood based on the linear eikonal
      equation. Last, we demonstrate that the front velocity is determined by the
      suppressed diffusivity of the reactants for L?l. 

PMID- 25768566
TI  - State transition induced by higher-order effects and background frequency.
AB  - The state transition between the Peregrine rogue wave and W-shaped traveling wave
      induced by higher-order effects and background frequency is studied. We find that
      this intriguing transition, described by an exact explicit rational solution, is
      consistent with the modulation instability (MI) analysis that involves a MI
      region and a stability region in a low perturbation frequency region. In
      particular, the link between the MI growth rate and the transition characteristic
      analytically demonstrates that the localization characteristic of transition is
      positively associated with the reciprocal of the zero-frequency growth rate.
      Furthermore, we investigate the case for nonlinear interplay of multilocalized
      waves. It is interesting that the interaction of second-order waves in the
      stability region features a line structure rather than an elastic interaction
      between two W-shaped traveling waves. 

PMID- 25768567
TI  - General approach for dealing with dynamical systems with spatiotemporal
      periodicities.
AB  - Dynamical systems often contain oscillatory forces or depend on periodic
      potentials. Time or space periodicity is reflected in the properties of these
      systems through a dependence on the parameters of their periodic terms. In this
      paper we provide a general theoretical framework for dealing with these kinds of
      systems, regardless of whether they are classical or quantum, stochastic or
      deterministic, dissipative or nondissipative, linear or nonlinear, etc. In
      particular, we are able to show that simple symmetry considerations determine, to
      a large extent, how their properties depend functionally on some of the
      parameters of the periodic terms. For the sake of illustration, we apply this
      formalism to find the functional dependence of the expectation value of the
      momentum of a Bose-Einstein condensate, described by the Gross-Pitaewskii
      equation, when it is exposed to a sawtooth potential whose amplitude is
      periodically modulated in time. We show that, by using this formalism, a small
      set of measurements is enough to obtain the functional form for a wide range of
      parameters. This can be very helpful when characterizing experimentally the
      response of systems for which performing measurements is costly or difficult. 

PMID- 25768568
TI  - Early effect in time-dependent, high-dimensional nonlinear dynamical systems with
      multiple resonances.
AB  - We investigate high-dimensional nonlinear dynamical systems exhibiting multiple
      resonances under adiabatic parameter variations. Our motivations come from
      experimental considerations where time-dependent sweeping of parameters is a
      practical approach to probing and characterizing the bifurcations of the system.
      The question is whether bifurcations so detected are faithful representations of
      the bifurcations intrinsic to the original stationary system. Utilizing a
      harmonically forced, closed fluid flow system that possesses multiple resonances
      and solving the Navier-Stokes equation under proper boundary conditions, we
      uncover the phenomenon of the early effect. Specifically, as a control parameter,
      e.g., the driving frequency, is adiabatically increased from an initial value,
      resonances emerge at frequency values that are lower than those in the
      corresponding stationary system. The phenomenon is established by numerical
      characterization of physical quantities through the resonances, which include the
      kinetic energy and the vorticity field, and a heuristic analysis based on the
      concept of instantaneous frequency. A simple formula is obtained which relates
      the resonance points in the time-dependent and time-independent systems. Our
      findings suggest that, in general, any true bifurcation of a nonlinear dynamical
      system can be unequivocally uncovered through adiabatic parameter sweeping, in
      spite of a shift in the bifurcation point, which is of value to experimental
      studies of nonlinear dynamical systems. 

PMID- 25768569
TI  - Chimera states on the route from coherence to rotating waves.
AB  - We report different types of chimera states in the Kuramoto model with inertia.
      They arise on the route from coherence, via so-called solitary states, to the
      rotating waves. We identify the wide region in parameter space, in which a
      different type of chimera state, i.e., the imperfect chimera state, which is
      characterized by a certain number of oscillators that have escaped from the
      synchronized chimera's cluster, appears. We describe a mechanism for the creation
      of chimera states via the appearance of the solitary states. Our findings reveal
      that imperfect chimera states represent characteristic spatiotemporal patterns at
      the transition from coherence to incoherence. 

PMID- 25768570
TI  - Linear instability of a zigzag pattern.
AB  - Interacting particles confined in a quasi-one-dimensional channel are physical
      systems which display various equilibrium patterns according to the interparticle
      interaction and the transverse confinement potential. Depending on the
      confinement, the particles may be distributed along a straight line, in a
      staggered row (zigzag), or in a configuration in which the linear and zigzag
      phases coexist (distorted zigzag). In order to clarify the conditions of
      existence of each configuration, we have studied the linear stability of the
      zigzag pattern. We find an acoustic transverse mode that destabilizes the zigzag
      configuration for short-range interaction potentials, and we calculate the
      interaction range above which this instability disappears. In particular, we
      recover the unconditional stability of zigzag patterns for Coulomb interactions.
      We show that the domain of existence for the distorted zigzag patterns is
      accurately described by our linear stability analysis. We also emphasize the
      complexity of finite size effects. Last, we provide a criterion for the onset of
      instability in the thermodynamic limit and propose a biphasic model that explains
      some characteristics of the distorted zigzag patterns. 

PMID- 25768571
TI  - Chimera states on the surface of a sphere.
AB  - A chimera state is a spatiotemporal pattern in which a network of identical
      coupled oscillators exhibits coexisting regions of asynchronous and synchronous
      oscillation. Two distinct classes of chimera states have been shown to exist:
      "spots" and "spirals." Here we study coupled oscillators on the surface of a
      sphere, a single system in which both spot and spiral chimera states appear. We
      present an analysis of the birth and death of spiral chimera states and show that
      although they coexist with spot chimeras, they are stable in disjoint regions of
      parameter space. 

PMID- 25768572
TI  - Charge flipping vortices in the discrete nonlinear Schrodinger trimer and
      hexamer.
AB  - We examine the existence and properties of charge flipping vortices (CFVs),
      vortices which periodically flip the topological charge, in three-site (trimer)
      and six-site (hexamer) discrete nonlinear Schrodinger lattices. We demonstrate
      numerically that CFVs exist as exact quasiperiodic solutions in continuous
      families which connect two different stationary solutions without topological
      charge, and that it is possible to interpret the dynamics of certain CFVs as the
      result of perturbations of these stationary solutions. The CFVs are calculated
      with high numerical accuracy and we may therefore accurately determine many of
      their properties, such as their energy and linear stability, and the CFVs are
      found to be stable over large parameter regimes. We also show that, like in
      earlier studies for lattices with a multiple of four sites, trimer and hexamer
      CFVs can be obtained by perturbing stationary constant amplitude vortices with
      certain linear eigenmodes. However, in contrast to the former case where the
      perturbation could be infinitesimal, the magnitude of the perturbations for
      trimers and hexamers must overcome a quite large threshold value. These CFVs may
      be interpreted as exact quasiperiodic CFVs, with a small perturbation applied.
      The concept of a charge flipping energy barrier is introduced and discussed. 

PMID- 25768573
TI  - Friction phenomena in the overdamped three-layer model.
AB  - An overdamped three-layer model consisting of two harmonic chains of interacting
      particles, representing the upper and the middle layers, which move over the
      substrate potential, is studied in the present paper. A dc+ac force is applied
      only on the upper harmonic chain, and dynamics of both layers are investigated.
      The results show that the dynamical mode locking and Shapiro steps appear not
      only in the upper layer but also in the middle one. It is noted that the motion
      of particles in the upper layer corresponds to the standard Frenkel-Kontorova
      model. The dependence of the Shapiro steps of the middle layer on the system
      parameters are determined. It is shown that the height of the first Shapiro step
      of the upper layer is unrelated to the interaction parameters of the particles of
      both the upper and the middle layers, while the height of the first Shapiro step
      of the middle layer depend only on the interaction parameters of the particles of
      the middle layers. Two critical forces which transfer from locked state to the
      sliding one of both the upper and the middle layers are also studied. They depend
      on the amplitude and the frequency of the external ac driving force. 

PMID- 25768574
TI  - Ultradiscrete kinks with supersonic speed in a layered crystal with realistic
      potentials.
AB  - In this paper we develop a dynamical model of the propagating nonlinear localized
      excitations, supersonic kinks, in the cation layer in a silicate mica crystal. We
      start from purely electrostatic Coulomb interaction and add the Ziegler-Biersack
      Littmark short-range repulsive potential and the periodic potential produced by
      other atoms of the lattice. The proposed approach allows the construction of
      supersonic kinks which can propagate in the lattice within a large range of
      energies and velocities. Due to the presence of the short-range repulsive
      component in the potential, the interparticle distances in the lattice kinks with
      high energy are limited by physically reasonable values. The introduction of the
      periodic lattice potential results in the important feature that the kinks
      propagate with the single velocity and single energy, which are independent on
      the excitation conditions. The unique average velocity of the supersonic kinks on
      the periodic substrate potential we relate with the kink amplitude of the
      relative particle displacements, which is determined by the interatomic distance
      corresponding to the minimum of the total, interparticle plus substrate, lattice
      potential. The found kinks are ultradiscrete and can be described with the "magic
      wave number" q=2pi/3a, which was previously revealed in the nonlinear sinusoidal
      waves and supersonic kinks in the Fermi-Pasta-Ulam lattice. The extreme
      discreteness of the observed supersonic kinks, with basically two particles
      moving at the same time, allows the detailed interpretation of their double-kink
      structure, which is not possible for the multikinks without an account for the
      lattice discreteness. Analytical calculations of the displacement patterns and
      energies of the supersonic kinks are confirmed by numerical simulations. The
      computed energy of the found supersonic kinks in the considered realistic lattice
      potential is in a good agreement with the experimental evidence for the transport
      of localized energetic excitations in silicate mica crystals between the points
      of ^{40}K recoil and subsequent sputtering. 

PMID- 25768575
TI  - Shear-flow-controlled mode selection in a nonlinear autocatalytic medium.
AB  - The effect of shear flow on mode selection and the length scale of patterns
      formed in a nonlinear autocatalytic reaction-diffusion model is investigated. We
      predict analytically the existence of transverse and longitudinal modes. The type
      of the selected mode strongly depends on the difference in the flow rates of the
      participating species, quantified by the differential flow parameter. Spatial
      structures are obtained by varying the length scale of individual modes and
      superposing them via the differential flow parameter. Our predictions are in line
      with numerical results obtained from lattice Boltzmann simulations. 

PMID- 25768576
TI  - Encoding by control of the symbolic dynamics emitted by a chaotic laser.
AB  - Application to a chaotic erbium-doped fiber laser of the digital encoding
      technique by control of its emitted symbolic dynamics is numerically tested.
      Criteria to select the better working conditions and the perturbation to be
      introduced in any control parameter are proposed. Once they are chosen, the
      procedure to prepare the system for control and the way to carry it out are
      described. It is shown that the general method cannot be blindly applied, but it
      must be adapted to the particular case under analysis for a good performance.
      Finally, in relation to a possible experimental implementation, influence of
      noise in the bit error rate of the communication system is discussed. 

PMID- 25768577
TI  - Partial synchronization and partial amplitude death in mesoscale network motifs.
AB  - We study the interplay between network topology and complex space-time patterns
      and introduce a concept to analytically predict complex patterns in networks of
      Stuart-Landau oscillators with linear symmetric and instantaneous coupling based
      solely on the network topology. These patterns consist of partial amplitude death
      and partial synchronization and are found to exist in large variety for all
      undirected networks of up to 5 nodes. The underlying concept is proved to be
      robust with respect to frequency mismatch and can also be extended to larger
      networks. In addition it directly links the stability of complete in-phase
      synchronization to only a small subset of topological eigenvalues of a network. 

PMID- 25768578
TI  - Transitional behavior in hydrodynamically coupled oscillators.
AB  - In this article we consider the complete set of synchronized and phase-locked
      states available to pairs of hydrodynamically coupled colloidal rotors,
      consisting of spherical beads driven about circular paths in the same, and in
      opposing senses. Oscillators such as these have previously been used as coarse
      grained, minimal models of beating cilia. Two mechanisms are known to be
      important in establishing synchrony. The first involves perturbation of the
      driving force, and the second involves deformation of the rotor trajectory. We
      demonstrate that these mechanisms are of similar strength, in the regime of
      interest, and interact to determine observed behavior. Combining analysis and
      simulation with experiments performed using holographic optical tweezers, we show
      how varying the amplitude of the driving force perturbation leads to a transition
      from synchronized to phase-locked states. Analogies with biological systems are
      discussed, as are implications for the design of biomimetic devices. 

PMID- 25768579
TI  - Robustness of chimera states for coupled FitzHugh-Nagumo oscillators.
AB  - Chimera states are complex spatio-temporal patterns that consist of coexisting
      domains of spatially coherent and incoherent dynamics. This counterintuitive
      phenomenon was first observed in systems of identical oscillators with symmetric
      coupling topology. Can one overcome these limitations? To address this question,
      we discuss the robustness of chimera states in networks of FitzHugh-Nagumo
      oscillators. Considering networks of inhomogeneous elements with regular coupling
      topology, and networks of identical elements with irregular coupling topologies,
      we demonstrate that chimera states are robust with respect to these perturbations
      and analyze their properties as the inhomogeneities increase. We find that
      modifications of coupling topologies cause qualitative changes of chimera states:
      additional random links induce a shift of the stability regions in the system
      parameter plane, gaps in the connectivity matrix result in a change of the
      multiplicity of incoherent regions of the chimera state, and hierarchical
      geometry in the connectivity matrix induces nested coherent and incoherent
      regions. 

PMID- 25768580
TI  - Noise robustness of unpredictability in a chaotic laser system: toward reliable
      physical random bit generation.
AB  - We introduce a concept of noise robustness in dynamical systems with noise and
      argue that this concept is essential to guarantee the reliability of physical
      random bit generators (RBGs). As an example of promising physical RBGs we
      consider a chaotic laser system and show that it has the property of noise
      robustness with respect to changes in the temporal correlation of the noise
      source. Moreover, employing a simple model of tangent space dynamics, we give a
      theoretical interpretation of the numerical results and in particular show that
      the Lyapunov exponent determines a theoretical boundary of a noise-robust region
      in parameter space. These theoretical results are expected to be significant not
      only for chaotic lasers, but also for a broad class of chaotic dynamical systems
      with correlated noise. 

PMID- 25768581
TI  - Breather solutions of the integrable quintic nonlinear Schrodinger equation and
      their interactions.
AB  - We present breather solutions of the quintic integrable equation of the
      Schrodinger hierarchy. This equation has terms describing fifth-order dispersion
      and matching nonlinear terms. Using a Darboux transformation, we derive first
      order and second-order breather solutions. These include first- and second-order
      rogue-wave solutions. To some extent, these solutions are analogous with the
      corresponding nonlinear Schrodinger equation (NLSE) solutions. However, the
      presence of a free parameter in the equation results in specific solutions that
      have no analogues in the NLSE case. We analyze new features of these solutions. 

PMID- 25768582
TI  - Emergent hybrid synchronization in coupled chaotic systems.
AB  - We evidence an interesting kind of hybrid synchronization in coupled chaotic
      systems where complete synchronization is restricted to only a subset of
      variables of two systems while other subset of variables may be in a phase
      synchronized state or desynchronized. Such hybrid synchronization is a generic
      emergent feature of coupled systems when a controller based coupling, designed by
      the Lyapunov function stability, is first engineered to induce complete
      synchronization in the identical case, and then a large parameter mismatch is
      introduced. We distinguish between two different hybrid synchronization regimes
      that emerge with parameter perturbation. The first, called hard hybrid
      synchronization, occurs when the coupled systems display global phase
      synchronization, while the second, called soft hybrid synchronization,
      corresponds to a situation where, instead, the global synchronization feature no
      longer exists. We verify the existence of both classes of hybrid synchronization
      in numerical examples of the Rossler system, a Lorenz-like system, and also in
      electronic experiment. 

PMID- 25768583
TI  - Characterization of the chaos-hyperchaos transition based on return times.
AB  - We discuss the problem of the detection of hyperchaotic oscillations in coupled
      nonlinear systems when the available information about this complex dynamical
      regime is very limited. We demonstrate the ability of diagnosing the chaos
      hyperchaos transition from return times into a Poincare section and show that an
      appropriate selection of the secant plane allows a correct estimation of two
      positive Lyapunov exponents (LEs) from even a single sequence of return times. We
      propose a generalized approach for extracting dynamics from point processes that
      allows avoiding spurious identification of the dynamical regime caused by
      artifacts. The estimated LEs are nearly close to their expected values if the
      second positive LE is essentially different from the largest one. If both
      exponents become nearly close, an underestimation of the second LE may be
      obtained. Nevertheless, distinctions between chaotic and hyperchaotic regimes are
      clearly possible. 

PMID- 25768584
TI  - Delay-induced remote synchronization in bipartite networks of phase oscillators.
AB  - We study a system of mismatched oscillators on a bipartite topology with time
      delay coupling, and analyze the synchronized states. For a range of parameters,
      when all oscillators lock to a common frequency, we find solutions such that
      systems within a partition are in complete synchrony, while there is lag
      synchronization between the partitions. Outside this range, such a solution does
      not exist and instead one observes scenarios of remote synchronization-namely,
      chimeras and individual synchronization, where either one or both of the
      partitions are synchronized independently. In the absence of time delay such
      states are not observed in phase oscillators. 

PMID- 25768585
TI  - Coarsening of stripe patterns: variations with quench depth and scaling.
AB  - The coarsening of stripe patterns when the system is evolved from random initial
      states is studied by varying the quench depth epsilon, which is a measure of
      distance from the transition point of the stripe phase. The dynamics of the
      growth of stripe order, which is characterized by two length scales, depends on
      the quench depth. The growth exponents of the two length scales vary continuously
      with epsilon. The decay exponents for free energy, stripe curvature, and
      densities of defects like grain boundaries and dislocations also show similar
      variation. This implies a breakdown of the standard picture of nonequilibrium
      dynamical scaling. In order to understand the variations with epsilon we propose
      an additional scaling with a length scale dependent on epsilon. The main
      contribution to this length scale comes from the "pinning potential," which is
      unique to systems where the order parameter is spatially periodic. The periodic
      order parameter gives rise to an epsilon-dependent potential, which can pin
      defects like grain boundaries, dislocations, etc. This additional scaling
      provides a compact description of variations of growth exponents with quench
      depth in terms of just one exponent for each of the length scales. The relaxation
      of free energy, stripe curvature, and the defect densities have also been related
      to these length scales. The study is done at zero temperature using Swift
      Hohenberg equation in two dimensions. 

PMID- 25768586
TI  - Localized vegetation patterns, fairy circles, and localized patches in arid
      landscapes.
AB  - We investigate the formation of localized structures with varying widths in one-
      and two-dimensional systems. The mechanism of stabilization is attributed to
      strongly nonlocal coupling mediated by a Lorentzian type of kernel. We show that,
      in addition to stable dips found recently [see, e.g. Fernandez-Oto et al., Phys.
      Rev. Lett. 110, 174101 (2013)], there are stable localized peaks which appear as
      a result of strongly nonlocal coupling. We applied this mechanism to arid
      ecosystems by considering a prototype model of a Nagumo type. In one dimension,
      we study the front connecting the stable uniformly vegetated state to the bare
      one under the effect of strongly nonlocal coupling. We show that strongly
      nonlocal coupling stabilizes both-dip and peak-localized structures. We show
      analytically and numerically that the width of a localized structure, which we
      interpret as a fairy circle, increases strongly with the aridity parameter. This
      prediction is in agreement with published observations. In addition, we predict
      that the width of localized patch decreases with the degree of aridity. Numerical
      results are in close agreement with analytical predictions.

PMID- 25768587
TI  - Dynamics and properties of waves in a modified Noguchi electrical transmission
      line.
AB  - We consider a modified Noguchi electrical transmission line and examine the
      effects of a linear capacitance C(s) on the wave characteristics while
      considering the semidiscrete approximation. It appears that wave modulations in
      the network are governed by a dispersive nonlinear Schrodinger equation whose
      coefficients are shown to be a function of C(s). We show that the use of this
      linear capacitance makes the filter more selective. We also show that the width
      of the unstable regions increases while that of the stable regions decreases with
      C(s) adding consequently the width of the frequency domain where bright solitons
      exist. Furthermore, we establish the existence of one more region (compared to
      the work of Marquie et al. [Marquie et al., Phys. Rev. E 49, 828 (1994)]) in the
      dispersion curve that allows the motion of envelope solitons of higher frequency
      in the system. Numerical and experimental investigations done on the model
      confirm our analytical predictions.

PMID- 25768588
TI  - Analyzing long-term correlated stochastic processes by means of recurrence
      networks: potentials and pitfalls.
AB  - Long-range correlated processes are ubiquitous, ranging from climate variables to
      financial time series. One paradigmatic example for such processes is fractional
      Brownian motion (fBm). In this work, we highlight the potentials and conceptual
      as well as practical limitations when applying the recently proposed recurrence
      network (RN) approach to fBm and related stochastic processes. In particular, we
      demonstrate that the results of a previous application of RN analysis to fBm [Liu
      et al. Phys. Rev. E 89, 032814 (2014)] are mainly due to an inappropriate
      treatment disregarding the intrinsic nonstationarity of such processes.
      Complementarily, we analyze some RN properties of the closely related stationary
      fractional Gaussian noise (fGn) processes and find that the resulting network
      properties are well-defined and behave as one would expect from basic conceptual
      considerations. Our results demonstrate that RN analysis can indeed provide
      meaningful results for stationary stochastic processes, given a proper selection
      of its intrinsic methodological parameters, whereas it is prone to fail to
      uniquely retrieve RN properties for nonstationary stochastic processes like fBm.

PMID- 25768589
TI  - Dynamics of intracranial electroencephalographic recordings from epilepsy
      patients using univariate and bivariate recurrence networks.
AB  - Recently Andrezejak et al. combined the randomness and nonlinear independence
      test with iterative amplitude adjusted Fourier transform (iAAFT) surrogates to
      distinguish between the dynamics of seizure-free intracranial
      electroencephalographic (EEG) signals recorded from epileptogenic (focal) and
      nonepileptogenic (nonfocal) brain areas of epileptic patients. However,
      stationarity is a part of the null hypothesis for iAAFT surrogates and thus
      nonstationarity can violate the null hypothesis. In this work we first propose
      the application of the randomness and nonlinear independence test based on
      recurrence network measures to distinguish between the dynamics of focal and
      nonfocal EEG signals. Furthermore, we combine these tests with both iAAFT and
      truncated Fourier transform (TFT) surrogate methods, which also preserves the
      nonstationarity of the original data in the surrogates along with its linear
      structure. Our results indicate that focal EEG signals exhibit an increased
      degree of structural complexity and interdependency compared to nonfocal EEG
      signals. In general, we find higher rejections for randomness and nonlinear
      independence tests for focal EEG signals compared to nonfocal EEG signals. In
      particular, the univariate recurrence network measures, the average clustering
      coefficient C and assortativity R, and the bivariate recurrence network measure,
      the average cross-clustering coefficient C(cross), can successfully distinguish
      between the focal and nonfocal EEG signals, even when the analysis is restricted
      to nonstationary signals, irrespective of the type of surrogates used. On the
      other hand, we find that the univariate recurrence network measures, the average
      path length L, and the average betweenness centrality BC fail to distinguish
      between the focal and nonfocal EEG signals when iAAFT surrogates are used.
      However, these two measures can distinguish between focal and nonfocal EEG
      signals when TFT surrogates are used for nonstationary signals. We also report an
      improvement in the performance of nonlinear prediction error N and nonlinear
      interdependence measure L used by Andrezejak et al., when TFT surrogates are used
      for nonstationary EEG signals. We also find that the outcome of the nonlinear
      independence test based on the average cross-clustering coefficient C(cross) is
      independent of the outcome of the randomness test based on the average clustering
      coefficient C. Thus, the univariate and bivariate recurrence network measures
      provide independent information regarding the dynamics of the focal and nonfocal
      EEG signals. In conclusion, recurrence network analysis combined with
      nonstationary surrogates can be applied to derive reliable biomarkers to
      distinguish between epileptogenic and nonepileptogenic brain areas using EEG
      signals.

PMID- 25768590
TI  - Stochastic mean-field formulation of the dynamics of diluted neural networks.
AB  - We consider pulse-coupled leaky integrate-and-fire neural networks with randomly
      distributed synaptic couplings. This random dilution induces fluctuations in the
      evolution of the macroscopic variables and deterministic chaos at the microscopic
      level. Our main aim is to mimic the effect of the dilution as a noise source
      acting on the dynamics of a globally coupled nonchaotic system. Indeed, the
      evolution of a diluted neural network can be well approximated as a fully pulse
      coupled network, where each neuron is driven by a mean synaptic current plus
      additive noise. These terms represent the average and the fluctuations of the
      synaptic currents acting on the single neurons in the diluted system. The main
      microscopic and macroscopic dynamical features can be retrieved with this
      stochastic approximation. Furthermore, the microscopic stability of the diluted
      network can be also reproduced, as demonstrated from the almost coincidence of
      the measured Lyapunov exponents in the deterministic and stochastic cases for an
      ample range of system sizes. Our results strongly suggest that the fluctuations
      in the synaptic currents are responsible for the emergence of chaos in this class
      of pulse-coupled networks. 

PMID- 25768591
TI  - Buoyancy-driven instabilities around miscible A+B->C reaction fronts: a general
      classification.
AB  - Upon contact between miscible solutions of reactants A and B along a horizontal
      interface in the gravity field, various buoyancy-driven instabilities can develop
      when an A+B->C reaction takes place and the density varies with the
      concentrations of the various chemicals. To classify the possible convective
      instability scenarios, we analyze the spatial dependence of the large time
      asymptotic density profiles as a function of the key parameters of the problem,
      which are the ratios of diffusion coefficients and of solutal expansion
      coefficients of species A, B, and C. We find that 62 different density profiles
      can develop in the reactive problem, whereas only 6 of them can be obtained in
      the nonreactive one. 

PMID- 25768592
TI  - Dynamics of viscous liquid bridges inside microchannels subject to external
      oscillatory flow.
AB  - We report on two-dimensional simulations of liquid bridges' dynamics inside
      microchannels of uniform wettability and subject to an external oscillatory flow
      rate. The oscillatory flow results in a zero net flow rate and its effects are
      compared to those of a stationary system. To handle the three phase contact lines
      motion, Cahn-Hilliard diffuse-interface formulation was used and the flow
      equations were solved using the finite element method with adaptively refined
      unstructured grids. The results indicate that the liquid bridge responds in three
      different ways depending on the substrate wettability properties and the
      frequency of the oscillatory flow. In particular below a critical frequency, the
      liquid bridge will rupture when the channel walls are philic or detach from the
      surface when they are phobic. However, at high frequencies, the liquid bridge
      shows a perpetual periodic oscillatory motion for both philic and phobic
      surfaces. Furthermore, an increase in the frequency of the flow velocity results
      in stabilization effects and a behavior approaching that of the stationary system
      where no rupture or detachment can be observed. This stable behavior is the
      direct result of less deformation of the liquid bridge due to the fast flow
      direction change and motion of contact lines on the solid substrate. Moreover, it
      was found that the flow velocity is out of phase with the footprint and throat
      lengths and that the latter two also show a phase difference. These differences
      were explained in terms of the motion of the two contact lines on the solid
      substrates and the deformation of the two fluid-fluid interfaces. 

PMID- 25768593
TI  - Evolution and stability of shock waves in dissipative gases characterized by
      activated inelastic collisions.
AB  - Previous experiments have revealed that shock waves driven through dissipative
      gases may become unstable, for example, in granular gases and in molecular gases
      undergoing strong relaxation effects. The mechanisms controlling these
      instabilities are not well understood. We successfully isolated and investigated
      this instability in the canonical problem of piston-driven shock waves
      propagating into a medium characterized by inelastic collision processes. We
      treat the standard model of granular gases, where particle collisions are taken
      as inelastic, with a constant coefficient of restitution. The inelasticity is
      activated for sufficiently strong collisions. Molecular dynamic simulations were
      performed for 30,000 particles. We find that all shock waves investigated become
      unstable, with density nonuniformities forming in the relaxation region. The
      wavelength of these fingers is found to be comparable to the characteristic
      relaxation thickness. Shock Hugoniot curves for both elastic and inelastic
      collisions were obtained analytically and numerically. Analysis of these curves
      indicates that the instability is not of the Bethe-Zeldovich-Thompson or D'yakov
      Kontorovich type. Analysis of the shock relaxation rates and rates for clustering
      in a convected fluid element with the same thermodynamic history ruled out the
      clustering instability of a homogeneous granular gas. Instead, wave
      reconstruction of the early transient evolution indicates that the onset of
      instability occurs during repressurization of the gas following the initial
      relaxation of the medium behind the lead shock. This repressurization gives rise
      to internal pressure waves in the presence of strong density gradients. This
      indicates that the mechanism of instability is more likely of the vorticity
      generating Richtmyer-Meshkov type, relying on the action of the inner pressure
      wave development during the transient relaxation.

PMID- 25768594
TI  - Observations of spontaneous oscillations in simple two-fluid networks.
AB  - We investigate the laminar flow of two-fluid mixtures inside a simple network of
      interconnected tubes. The fluid system is composed of two miscible Newtonian
      fluids of different viscosity which do not mix and remain as nearly distinct
      phases. Downstream of a diverging network junction the two fluids do not
      necessarily split in equal fraction and thus heterogeneity is introduced into
      network. We find that in the simplest network, a single loop with one inlet and
      one outlet, under steady inlet conditions, the flow rates and distribution of the
      two fluids within the network loop can undergo persistent spontaneous
      oscillations. We develop a simple model which highlights the basic mechanism of
      the instability and we demonstrate that the model can predict the region of
      parameter space where oscillations exist. The model predictions are in good
      agreement with experimental observations. 

PMID- 25768595
TI  - Normal velocity freeze-out of the Richtmyer-Meshkov instability when a
      rarefaction is reflected.
AB  - The Richtmyer-Meshkov instability (RMI) develops when a shock front hits a
      rippled contact surface separating two different fluids. After the incident shock
      refraction, a transmitted shock is always formed and another shock or a
      rarefaction is reflected back. The pressure-entropy-vorticity fields generated by
      the rippled wave fronts are responsible for the generation of hydrodynamic
      perturbations in both fluids. In linear theory, the contact surface ripple
      reaches an asymptotic normal velocity which is dependent on the incident shock
      Mach number, fluids density ratio, and compressibilities. It was speculated in
      the past about the possibility of getting a zero value for the asymptotic normal
      velocity, a phenomenon that was called "freeze-out" [G. Fraley, Phys. Fluids 29,
      376 (1986); K. Mikaelian, Phys. Fluids 6, 356 (1994), A. L. Velikovich et al.,
      Phys. Plasmas 8, 592 (2001)]. In a previous paper, freeze-out was studied for the
      case when a shock is reflected at the contact surface [J. G. Wouchuk and K.
      Nishihara, Phys. Rev. E 70, 026305 (2004)]. In this work the freeze-out of the
      RMI is studied for the case in which a rarefaction is reflected back. Two
      different regimes are found: nearly equal preshock densities at the interface at
      any shock intensity, and very large density difference for strong shocks. The
      contour curves that relate shock Mach number and preshock density ratio are
      obtained in both regimes for fluids with equal and different compressibilities.
      An analysis of the temporal evolution of different cases of freeze-out is shown.
      It is seen that the freeze-out is the result of the interaction between the
      unstable interface and the rippled wave fronts. As a general and qualitative
      criterion to look for freeze-out situations, it is seen that a necessary
      condition for freeze-out is the same orientation for the tangential velocities
      generated at each side of the contact surface at t=0+. A comparison with the
      results of previous works is also shown.

PMID- 25768596
TI  - Marangoni instability of a liquid film flow with viscous dissipation.
AB  - A linear stability analysis of a thin liquid film flowing over a plate is
      performed. The plate is considered as impermeable and adiabatic. The upper
      surface of the film is assumed to be a free boundary with a non-negligible
      surface tension, characterized by a Robin thermal boundary condition. The
      thermoconvective instability is generated by the interplay between the heating
      due to viscous dissipation and the temperature-dependent surface tension at the
      free boundary. A basic parallel flow, arbitrarily oriented, is assumed and the
      basic temperature profile is determined analytically. In order to investigate the
      linear stability of the system, the normal mode method is employed. A system of
      ordinary differential equations defining an eigenvalue problem is thus obtained.
      The case of longitudinal rolls, where the base flow velocity is parallel to the
      axis rolls, is solved both analytically and numerically. Other possible
      inclinations of the base flow are investigated by means of a numerical procedure
      based on combining the Runge-Kutta and the shooting methods. 

PMID- 25768597
TI  - Wall-mode instability in plane shear flow of viscoelastic fluid over a deformable
      solid.
AB  - The linear stability analysis of a plane Couette flow of an Oldroyd-B
      viscoelastic fluid past a flexible solid medium is carried out to investigate the
      role of polymer addition in the stability behavior. The system consists of a
      viscoelastic fluid layer of thickness R, density rho, viscosity eta, relaxation
      time lambda, and retardation time betalambda flowing past a linear elastic solid
      medium of thickness HR, density rho, and shear modulus G. The emphasis is on the
      high-Reynolds-number wall-mode instability, which has recently been shown in
      experiments to destabilize the laminar flow of Newtonian fluids in soft-walled
      tubes and channels at a significantly lower Reynolds number than that for flows
      in rigid conduits. For Newtonian fluids, the linear stability studies have shown
      that the wall modes become unstable when flow Reynolds number exceeds a certain
      critical value Re(c) which scales as Sigma(3/4), where Reynolds number
      Re=rhoVR/eta,V is the top-plate velocity, and dimensionless parameter
      Sigma=rhoGR(2)/eta(2) characterizes the fluid-solid system. For high-Reynolds
      number flow, the addition of polymer tends to decrease the critical Reynolds
      number in comparison to that for the Newtonian fluid, indicating a destabilizing
      role for fluid viscoelasticity. Numerical calculations show that the critical
      Reynolds number could be decreased by up to a factor of 10 by the addition of
      small amount of polymer. The critical Reynolds number follows the same scaling
      Re(c)~Sigma(3/4) as the wall modes for a Newtonian fluid for very high Reynolds
      number. However, for moderate Reynolds number, there exists a narrow region in
      beta-H parametric space, corresponding to very dilute polymer solution
      (0.9?beta<1) and thin solids (H?1.1), in which the addition of polymer tends to
      increase the critical Reynolds number in comparison to the Newtonian fluid. Thus,
      Reynolds number and polymer properties can be tailored to either increase or
      decrease the critical Reynolds number for unstable modes, thus providing an
      additional degree of control over the laminar-turbulent transition.

PMID- 25768598
TI  - Dewetting films with inclined contact lines.
AB  - A partially wetting plate withdrawn from a liquid reservoir causes the deposition
      of a liquid film that is characterized by inclined contact lines. It has been
      experimentally indicated that the normal component of the contact-line velocity
      relative to the plate remains constant and is independent of the inclination
      angles, a fact that has never theoretically been justified. We demonstrate, in
      the framework of lubrication theory, that the speed-angle independence is only
      approximate and the normal velocity actually exhibits a weak decrease with the
      inclination angle of the contact line. This correlation is attributed to the
      variation of the effective separation of microscopic and macroscopic length
      scales. In addition, the inclination of the contact line results in a tangential
      flux of the liquid, which is confined in the vicinity of the contact line. Simple
      scaling relations are provided for both the normal velocity and the tangential
      flux. 

PMID- 25768599
TI  - Non-Newtonian flow effects on the coalescence and mixing of initially stationary
      droplets of shear-thinning fluids.
AB  - The coalescence of two initially stationary droplets of shear-thinning fluids in
      a gaseous environment is investigated numerically using the lattice Boltzmann
      method, with particular interest in non-Newtonian flow effects on the internal
      mixing subsequent to coalescence. Coalescence of equal-sized droplets, with one
      being Newtonian while the other is non-Newtonian, leads to the non-Newtonian
      droplet wrapping around the Newtonian one and hence minimal fine-scale mixing.
      For unequal-sized droplets, mixing is greatly promoted if both droplets are shear
      thinning. When only one of the droplets is shear-thinning, the non-Newtonian
      effect from the smaller droplet is found to be significantly more effective than
      that from the larger droplet in facilitating internal jetlike mixing. Parametric
      study with the Carreau-Yasuda model indicates that the phenomena are universal to
      a wide range of shear-thinning fluids, given that the extent of shear thinning
      reaches a certain level, and the internal jet tends to be thicker and develops
      more rapidly with increasing extent of the shear-thinning effect. 

PMID- 25768600
TI  - Numerical and experimental study of an invisibility carpet in a water channel.
AB  - We propose a numerical and an experimental study of an invisibility carpet for
      linear water waves. In the first part, we introduce the concept of an
      invisibility carpet in the case of linear water waves and apply this concept for
      a bounded problem: a wavetank. In the second part, we study a simpler case where
      we attempt to render invisible a vertical dihedral at the end of a wavetank. This
      is done by placing a structure consisting of 18 vertical poles with trapezoidal
      cross-sections in front of the dihedral. For these two configurations, with and
      without the carpet, we focus on the far-field reflected wave consisting of an
      inline mode and the first sloshing (plus progressive) mode. We show that our
      design achieves invisibility. 

PMID- 25768601
TI  - Generalization of Darcy's law for Bingham fluids in porous media: from flow-field
      statistics to the flow-rate regimes.
AB  - In this paper, we numerically investigate the statistical properties of the
      nonflowing areas of Bingham fluid in two-dimensional porous media. First, we
      demonstrate that the size probability distribution of the unyielded clusters
      follows a power-law decay with a large size cutoff. This cutoff is shown to
      diverge following a power law as the imposed pressure drop tends to a critical
      value. In addition, we observe that the exponents are almost identical for two
      different types of porous media. Finally, those scaling properties allow us to
      account for the quadratic relationship between the pressure gradient and
      velocity. 

PMID- 25768602
TI  - Optimal design of Purcell's three-link swimmer.
AB  - In this paper we address the question of the optimal design for the Purcell three
      link swimmer. More precisely, we investigate the best link length ratio which
      maximizes its displacement. The dynamics of the swimmer is expressed as an
      ordinary differential equation, using the resistive force theory. Among a set of
      optimal strategies of deformation (strokes), we provide an asymptotic estimate of
      the displacement for small deformations, from which we derive the optimal link
      ratio. Numerical simulations are in good agreement with this theoretical estimate
      and also cover larger amplitudes of deformation. Compared with the classical
      design of the Purcell swimmer, we observe a gain in displacement of roughly 60%. 

PMID- 25768603
TI  - Numerical investigation of dynamic effects for sliding drops on wetting defects.
AB  - The ability to trap or deflect sliding drops is of great interest in
      microfluidics, as it has several technological applications, ranging from self
      cleaning and fog harvesting surfaces to laboratory-on-a-chip devices. We present
      a three-dimensional numerical model that describes sliding droplets interacting
      with wetting defects of variable strength and size. This approach provides
      relevant insight if compared to simplified analytic models, as it allows us to
      assess the relevance of the internal degrees of freedom of the droplet. We
      observe that the deformation of the drop enhances the effective strength and
      range of the defect, and we quantify this effect by comparison to a point-mass
      model. We also analyze the role of the steepness and strength of the defect on
      the drop motion, observing that small, strong defects are more effective at
      trapping than large, shallow traps of same excess surface energy. Finally, our
      results show quantitative agreement with previously reported electrowetting
      experiments, suggesting a universal behavior in droplet trapping that does not
      depend strongly on the nature of the defect. 

PMID- 25768604
TI  - Self-propulsion of a spherical electric or magnetic microbot in a polar viscous
      fluid.
AB  - The self-propulsion of a sphere immersed in a polar liquid or ferrofluid is
      studied on the basis of ferrohydrodynamics. In the electrical case an oscillating
      charge density located inside the sphere generates an electrical field that
      polarizes the fluid. The lag of polarization with respect to the electrical field
      due to relaxation generates a time-independent electrical torque density acting
      on the fluid, causing it to move. The resulting propulsion velocity of the sphere
      is calculated in perturbation theory to second order in powers of the charge
      density. 

PMID- 25768605
TI  - Free-path distribution and Knudsen-layer modeling for gaseous flows in the
      transition regime.
AB  - In this paper, we use molecular dynamics (MD) simulations to study the mean free
      path distribution of nonequilibrium gases in micronanochannel and to model the
      Knudsen (Kn) layer effect. It is found that the mean free path is significantly
      reduced near the wall and rather insensitive to flow types (Poiseuille or
      Couette). The Cercignani relation between the mean free path and the viscosity is
      adopted to capture the velocity behavior of the special zone in the framework of
      the extended Navier-Stokes (NS) equations. MD simulations of flows are carried
      out at different Kn numbers. Results are then compared with the theoretical
      model. 

PMID- 25768606
TI  - Saffman-Taylor fingers with kinetic undercooling.
AB  - The mathematical model of a steadily propagating Saffman-Taylor finger in a Hele
      Shaw channel has applications to two-dimensional interacting streamer discharges
      which are aligned in a periodic array. In the streamer context, the relevant
      regularization on the interface is not provided by surface tension but instead
      has been postulated to involve a mechanism equivalent to kinetic undercooling,
      which acts to penalize high velocities and prevent blow-up of the unregularized
      solution. Previous asymptotic results for the Hele-Shaw finger problem with
      kinetic undercooling suggest that for a given value of the kinetic undercooling
      parameter, there is a discrete set of possible finger shapes, each analytic at
      the nose and occupying a different fraction of the channel width. In the limit in
      which the kinetic undercooling parameter vanishes, the fraction for each family
      approaches 1/2, suggesting that this "selection" of 1/2 by kinetic undercooling
      is qualitatively similar to the well-known analog with surface tension. We treat
      the numerical problem of computing these Saffman-Taylor fingers with kinetic
      undercooling, which turns out to be more subtle than the analog with surface
      tension, since kinetic undercooling permits finger shapes which are corner-free
      but not analytic. We provide numerical evidence for the selection mechanism by
      setting up a problem with both kinetic undercooling and surface tension and
      numerically taking the limit that the surface tension vanishes. 

PMID- 25768607
TI  - Resonant and antiresonant bouncing droplets.
AB  - When placed onto a vibrating liquid bath, a droplet may adopt a permanent
      bouncing behavior, depending on both the forcing frequency and the forcing
      amplitude. The relationship between the droplet deformations and the bouncing
      mechanism is studied experimentally and theoretically through an asymmetric and
      dissipative bouncing spring model. Antiresonance phenomena are evidenced.
      Experiments and theoretical predictions show that both resonance at specific
      frequencies and antiresonance at Rayleigh frequencies play crucial roles in the
      bouncing mechanism. In particular, we show that they could be exploited for
      bouncing droplet size selection. 

PMID- 25768608
TI  - Decoupling translational and rotational effects on the phase synchronization of
      rotating helices.
AB  - The locomotion of swimming microorganisms often relies on synchronized motions;
      examples include the bundling of flagella and metachronal coordination of cilia.
      It is now generally accepted that such behavior can result from hydrodynamic
      interactions alone. In this paper we consider the interactions between two side
      by-side rigid helices driven by constant torques. We use the method of
      regularized Stokeslets to simulate an end-pinned model, in which restoring forces
      and torques are applied at one end of each helix. This allows us to decouple the
      respective effects of translation and rotation on phase synchronization. We find
      that while translational freedom leads to synchrony, rotational freedom can
      result in either synchrony or antisynchrony, depending on the stiffness of the
      system. In addition, we characterize the nature of the physical mechanisms
      driving these behaviors, focusing on the individual effects of each applied force
      and torque. For translational freedom, there is a single underlying mechanism in
      which the interaction forces indirectly influence the helix rotation rates.
      Multiple mechanisms are at play for rotational freedom: the interaction torques
      may exert either direct or indirect influence depending on stiffness. These
      characterizations are important to the future development of reduced-order
      models, which should capture not only the expected end behaviors (synchrony or
      antisynchrony), but also the nature of the driving mechanisms. 

PMID- 25768609
TI  - Low-to-moderate Reynolds number swirling flow in an annular channel with a
      rotating end wall.
AB  - This paper presents a new method for solving analytically the axisymmetric
      swirling flow generated in a finite annular channel from a rotating end wall,
      with no-slip boundary conditions along stationary side walls and a slip condition
      along the free surface opposite the rotating floor. In this case, the end-driven
      swirling flow can be described from the coupling between an azimuthal shear flow
      and a two-dimensional meridional flow driven by the centrifugal force along the
      rotating floor. A regular asymptotic expansion based on a small but finite
      Reynolds number is used to calculate centrifugation-induced first-order
      correction to the azimuthal Stokes flow obtained as the solution at leading
      order. For solving the first-order problem, the use of an integral boundary
      condition for the vorticity is found to be a convenient way to attribute boundary
      conditions in excess for the stream function to the vorticity. The annular
      geometry is characterized by both vertical and horizontal aspect ratios, whose
      respective influences on flow patterns are investigated. The vertical aspect
      ratio is found to involve nontrivial changes in flow patterns essentially due to
      the role of corner eddies located on the left and right sides of the rotating
      floor. The present analytical method can be ultimately extended to cylindrical
      geometries, irrespective of the surface opposite the rotating floor: a wall or a
      free surface. It can also serve as an analytical tool for monitoring confined
      rotating flows in applications related to surface viscosimetry or crystal growth
      from the melt. 

PMID- 25768610
TI  - Azimuthal field instability in a confined ferrofluid.
AB  - We report the development of interfacial ferrohydrodynamic instabilities when an
      initially circular bubble of a nonmagnetic inviscid fluid is surrounded by a
      viscous ferrofluid in the confined geometry of a Hele-Shaw cell. The fluid-fluid
      interface becomes unstable due to the action of magnetic forces induced by an
      azimuthal field produced by a straight current-carrying wire that is normal to
      the cell plates. In this framework, a pattern formation process takes place
      through the interplay between magnetic and surface tension forces. By employing a
      perturbative mode-coupling approach we investigate analytically both linear and
      intermediate nonlinear regimes of the interface evolution. As a result, useful
      analytical information can be extracted regarding the destabilizing role of the
      azimuthal field at the linear level, as well as its influence on the interfacial
      pattern morphology at the onset of nonlinear effects. Finally, a vortex sheet
      formalism is used to access fully nonlinear stationary solutions for the two
      fluid interface shapes. 

PMID- 25768611
TI  - Bidirectional energy cascade in surface capillary waves.
AB  - Based on an experiment and simulations, we report that an energy cascade in
      surface capillary waves can be bidirectional, that is, can simultaneously flow
      towards large and small wavelength scales from the pumping scales. The
      bidirectional energy cascade provides an effective global coupling mechanism
      between the scales. We show that formation of the bidirectional cascade leads to
      creation of large-scale, large-amplitude waves on the fluid surface. 

PMID- 25768612
TI  - Permutation entropy and statistical complexity analysis of turbulence in
      laboratory plasmas and the solar wind.
AB  - The Bandt-Pompe permutation entropy and the Jensen-Shannon statistical complexity
      are used to analyze fluctuating time series of three different turbulent plasmas:
      the magnetohydrodynamic (MHD) turbulence in the plasma wind tunnel of the
      Swarthmore Spheromak Experiment (SSX), drift-wave turbulence of ion saturation
      current fluctuations in the edge of the Large Plasma Device (LAPD), and fully
      developed turbulent magnetic fluctuations of the solar wind taken from the Wind
      spacecraft. The entropy and complexity values are presented as coordinates on the
      CH plane for comparison among the different plasma environments and other
      fluctuation models. The solar wind is found to have the highest permutation
      entropy and lowest statistical complexity of the three data sets analyzed. Both
      laboratory data sets have larger values of statistical complexity, suggesting
      that these systems have fewer degrees of freedom in their fluctuations, with SSX
      magnetic fluctuations having slightly less complexity than the LAPD edge I(sat).
      The CH plane coordinates are compared to the shape and distribution of a spectral
      decomposition of the wave forms. These results suggest that fully developed
      turbulence (solar wind) occupies the lower-right region of the CH plane, and that
      other plasma systems considered to be turbulent have less permutation entropy and
      more statistical complexity. This paper presents use of this statistical analysis
      tool on solar wind plasma, as well as on an MHD turbulent experimental plasma.

PMID- 25768613
TI  - Ion potential in warm dense matter: wake effects due to streaming degenerate
      electrons.
AB  - The effective dynamically screened potential of a classical ion in a stationary
      flowing quantum plasma at finite temperature is investigated. This is a key
      quantity for thermodynamics and transport of dense plasmas in the warm-dense
      matter regime. This potential has been studied before within hydrodynamic
      approaches or based on the zero temperature Lindhard dielectric function. Here we
      extend the kinetic analysis by including the effects of finite temperature and of
      collisions based on the Mermin dielectric function. The resulting ion potential
      exhibits an oscillatory structure with attractive minima (wakes) and, thus,
      strongly deviates from the static Yukawa potential of equilibrium plasmas. This
      potential is analyzed in detail for high-density plasmas with values of the
      Brueckner parameter in the range 0.1<=r(s)<=1 for a broad range of plasma
      temperature and electron streaming velocity. It is shown that wake effects become
      weaker with increasing temperature of the electrons. Finally, we obtain the
      minimal electron streaming velocity for which attraction between ions occurs.
      This velocity turns out to be less than the electron Fermi velocity. Our results
      allow for reliable predictions of the strength of wake effects in nonequilibrium
      quantum plasmas with fast streaming electrons showing that these effects are
      crucial for transport under warm-dense-matter conditions, in particular for laser
      matter interaction, electron-ion temperature equilibration, and stopping power.

PMID- 25768614
TI  - Ion separation effects in mixed-species ablators for inertial-confinement-fusion
      implosions.
AB  - Recent efforts to demonstrate significant self-heating of the fuel and eventual
      ignition at the National Ignition Facility make use of plastic (CH) ablators [O.
      A. Hurricane et al., Phys. Plasmas 21, 056314 (2014)]. Mainline simulation
      techniques for modeling CH capsule implosions treat the ablator as an average
      atom fluid and neglect potential species separation phenomena. The mass-ablation
      process for a mixture is shown to lead to the potential for species separation,
      parasitic energy loss according to thermodynamic arguments, and reduced rocket
      efficiency. A generalized plasma barometric formula for a multispecies
      concentration gradient that includes collisionality and steady flows in spherical
      geometry is presented. A model based on plasma expansion into a vacuum is used to
      interpret reported experimental evidence for ablator species separation in an
      inertial-confinement-fusion target [J. S. Ross et al., Rev. Sci. Instrum. 83,
      10E323 (2012)]. The possibility of "runaway" hydrogen ions in the thermoelectric
      field of the ablation front is conjectured.

PMID- 25768615
TI  - Role of charge transfer in heavy-ion-beam-plasma interactions at intermediate
      energies.
AB  - In this paper we investigate the influence of the plasma properties on the charge
      state distribution of a swift heavy ion beam interacting with a plasma. The main
      finding is that the charge state in plasma can be lower than in cold matter. The
      charge state distribution is determined by the ionization and recombination rates
      which are balancing each other out. Both, ionization and recombination rates, as
      well as atomic excitation and decay rates, depend on the plasma parameters in
      different ways. These effects have been theoretically studied by Monte Carlo
      simulations on the example of an argon ion beam at an energy of 4MeV/u in a
      carbon plasma. This study covers a plasma parameter space ranging from ion
      densities from 10(18) to 10(23) cm(-3) and electron temperatures from 10 to 200
      eV.

PMID- 25768616
TI  - Ab initio calculation of shocked xenon reflectivity.
AB  - Reflectivity of shocked compressed xenon plasma is calculated within the
      framework of the density functional theory approach. Dependencies on the
      frequency of incident radiation and on the plasma density are analyzed. The
      Fresnel formula for the reflectivity is used. The longitudinal expression in the
      long-wavelength limit is applied for the calculation of the imaginary part of the
      dielectric function. The real part of the dielectric function is calculated by
      means of the Kramers-Kronig transformation. The results are compared with
      experimental data. The approach for the calculation of plasma frequency is
      developed. 

PMID- 25768617
TI  - Equations of state, transport properties, and compositions of argon plasma:
      combination of self-consistent fluid variation theory and linear response theory.
AB  - A consistent theoretical model that can be applied in a wide range of densities
      and temperatures is necessary for understanding the variation of a material's
      properties during compression and heating. Taking argon as an example, we show
      that the combination of self-consistent fluid variational theory and linear
      response theory is a promising route for studying warm dense matter. Following
      this route, the compositions, equations of state, and transport properties of
      argon plasma are calculated in a wide range of densities (0.001-20 g/cm(3)) and
      temperatures (5-100 kK). The obtained equations of state and electrical
      conductivities are found in good agreement with available experimental data. The
      plasma phase transition of argon is observed at temperatures below 30 kK and
      density about 2-6g/cm(3). The minimum density for the metallization of argon is
      found to be about 5.8 g/cm(3), occurring at 30-40 kK. The effects of many
      particle correlations and dynamic screening on the electrical conductivity are
      also discussed through the effective potentials.

PMID- 25768618
TI  - Self-generated magnetic dipoles in weakly magnetized beam-plasma system.
AB  - A self-generation mechanism of magnetic dipoles and the anomalous energy
      dissipation of fast electrons in a magnetized beam-plasma system are presented.
      Based on two-dimensional particle-in-cell simulations, it is found that the
      magnetic dipoles are self-organized and play important roles in the beam electron
      energy dissipation. These dipoles drift slowly in the direction of the return
      flow with a quasisteady velocity, which depends upon the magnetic amplitude of
      the dipole and the imposed external magnetic field. This dipole formation
      provides a mechanism for the anomalous energy dissipation of a relativistic
      electron beam, which would play an important role in collisionless shock and ion
      shock acceleration. 

PMID- 25768619
TI  - Practical expressions for the internal energy and pressure of Yukawa fluids.
AB  - Simple practical expressions that allow estimation of thermodynamic properties of
      Yukawa fluids in a wide range of coupling, up to the fluid-solid phase
      transition, are presented. These expressions demonstrate excellent agreement with
      the available results from numerical simulations. The approach provides simple
      and accurate tools to estimate thermodynamic properties of Yukawa fluids and
      related systems in a broad range of parameters. 

PMID- 25768620
TI  - Symmetry breaking of solitons in two-dimensional complex potentials.
AB  - Symmetry breaking is reported for continuous families of solitons in the
      nonlinear Schrodinger equation with a two-dimensional complex potential. This
      symmetry breaking is forbidden in generic complex potentials. However, for a
      special class of partially parity-time-symmetric potentials, it is allowed. At
      the bifurcation point, two branches of asymmetric solitons bifurcate out from the
      base branch of symmetry-unbroken solitons. Stability of these solitons near the
      bifurcation point are also studied, and two novel properties for the bifurcated
      asymmetric solitons are revealed. One is that at the bifurcation point, zero and
      simple imaginary linear-stability eigenvalues of asymmetric solitons can move
      directly into the complex plane and create oscillatory instability. The other is
      that the two bifurcated asymmetric solitons, even though having identical powers
      and being related to each other by spatial mirror reflection, can possess
      different types of unstable eigenvalues and thus exhibit nonreciprocal nonlinear
      evolutions under random-noise perturbations. 

PMID- 25768621
TI  - Symmetric solitonic excitations of the (1 + 1)-dimensional Abelian-Higgs
      classical vacuum.
AB  - We study the classical dynamics of the Abelian-Higgs model in (1 + 1) space-time
      dimensions for the case of strongly broken gauge symmetry. In this limit the
      wells of the potential are almost harmonic and sufficiently deep, presenting a
      scenario far from the associated critical point. Using a multiscale perturbation
      expansion, the equations of motion for the fields are reduced to a system of
      coupled nonlinear Schrodinger equations. Exact solutions of the latter are used
      to obtain approximate analytical solutions for the full dynamics of both the
      gauge and Higgs field in the form of oscillons and oscillating kinks. Numerical
      simulations of the exact dynamics verify the validity of these solutions. We
      explore their persistence for a wide range of the model's single parameter, which
      is the ratio of the Higgs mass (m(H)) to the gauge-field mass (m(A)). We show
      that only oscillons oscillating symmetrically with respect to the "classical
      vacuum," for both the gauge and the Higgs field, are long lived. Furthermore,
      plane waves and oscillating kinks are shown to decay into oscillon-like patterns,
      due to the modulation instability mechanism.

PMID- 25768622
TI  - Stability of optical solitons in parity-time-symmetric optical lattices with
      competing cubic and quintic nonlinearities.
AB  - The existence and stability of optical solitons in the semi-infinite gap of
      parity-time (PT)-symmetric optical lattices with competing cubic and quintic
      nonlinearities are investigated numerically. The fundamental and dipole solitons
      can exist only with focusing quintic nonlinearity; however, they are always
      linearly unstable. With the competing effect between cubic and quintic
      nonlinearities, the strength of the quintic nonlinearity should be larger than a
      threshold for the solitons' existence when the strength of the focusing cubic
      nonlinearity is fixed. The stability of both fundamental and dipole solitons is
      studied in detail. When the strength of the focusing quintic nonlinearity is
      fixed, solitons can exist at the whole interval of the strength of the cubic
      nonlinearity, but only a small part of the fundamental solitons are stable. We
      also study numerically nonlinear evolution of stable and unstable PT solitons
      under perturbation. 

PMID- 25768623
TI  - Acoustic solitons in waveguides with Helmholtz resonators: transmission line
      approach.
AB  - We report experimental results and study theoretically soliton formation and
      propagation in an air-filled acoustic waveguide side loaded with Helmholtz
      resonators. We propose a theoretical modeling of the system, which relies on a
      transmission-line approach, leading to a nonlinear dynamical lattice model. The
      latter allows for an analytical description of the various soliton solutions for
      the pressure, which are found by means of dynamical systems and multiscale
      expansion techniques. These solutions include Boussinesq-like and Korteweg-de
      Vries pulse-shaped solitons that are observed in the experiment, as well as
      nonlinear Schrodinger envelope solitons, that are predicted theoretically. The
      analytical predictions are in excellent agreement with direct numerical
      simulations and in qualitative agreement with the experimental observations. 

PMID- 25768624
TI  - Optical rogue waves associated with the negative coherent coupling in an
      isotropic medium.
AB  - Optical rogue waves of the coupled nonlinear Schrodinger equations with negative
      coherent coupling, which describe the propagation of orthogonally polarized
      optical waves in an isotropic medium, are reported. We construct and discuss a
      family of the vector rogue-wave solutions, including the bright rogue waves, four
      petaled rogue waves, and dark rogue waves. A bright rogue wave without a valley
      can split up, giving birth to two bright rogue waves, and an eye-shaped rogue
      wave can split up, giving birth to two dark rogue waves. 

PMID- 25768625
TI  - Conductivity of periodic composites made of matrix and polydispersed aggregates.
AB  - We present closed-form expressions of the effective conductivity of composites
      made of matrix and impenetrable polydispersed particles. The approach developed
      in a recent work has been generalized to treat periodic multiphase composite
      materials. Particular cases including orthorhombic arrangements of spherical or
      spheroidal inclusions and random distributions of spheres are considered where
      simple closed-form expressions are obtained. The case of random distributions
      allows us to recover Mori-Tanaka estimation after introducing partial structure
      factors as a statistical information on the microstructure. 

PMID- 25768626
TI  - Detecting radiation reaction at moderate laser intensities.
AB  - We propose a new method of detecting radiation reaction effects in the motion of
      particles subjected to laser pulses of moderate intensity and long duration. The
      effect becomes sizable for particles that gain almost no energy through the
      interaction with the laser pulse. Hence, there are regions of parameter space in
      which radiation reaction is actually the dominant influence on charged particle
      motion. 

PMID- 25768627
TI  - Nonlinear resonances and energy transfer in finite granular chains.
AB  - In the present work we test experimentally and compute numerically the stability
      and dynamics of harmonically driven monoatomic granular chains composed of an
      increasing number of particles N(N=1-50). In particular, we investigate the
      inherent effects of dissipation and finite size on the evolution of bifurcation
      instabilities in the statically compressed case. The findings of the study
      suggest that the nonlinear bifurcation phenomena, which arise due to finite size,
      can be useful for efficient energy transfer away from the drive frequency in
      transmitted waves. 

PMID- 25768628
TI  - Soliton transport in tubular networks: transmission at vertices in the shrinking
      limit.
AB  - Soliton transport in tubelike networks is studied by solving the nonlinear
      Schrodinger equation (NLSE) on finite thickness ("fat") graphs. The dependence of
      the solution and of the reflection at vertices on the graph thickness and on the
      angle between its bonds is studied and related to a special case considered in
      our previous work, in the limit when the thickness of the graph goes to zero. It
      is found that both the wave function and reflection coefficient reproduce the
      regime of reflectionless vertex transmission studied in our previous work. 

PMID- 25768629
TI  - Bilinearization of the generalized coupled nonlinear Schrodinger equation with
      variable coefficients and gain and dark-bright pair soliton solutions.
AB  - We investigate coupled nonlinear Schrodinger equations (NLSEs) with variable
      coefficients and gain. The coupled NLSE is a model equation for optical soliton
      propagation and their interaction in a multimode fiber medium or in a fiber
      array. By using Hirota's bilinear method, we obtain the bright-bright, dark
      bright combinations of a one-soliton solution (1SS) and two-soliton solutions
      (2SS) for an n-coupled NLSE with variable coefficients and gain. Crucial
      properties of two-soliton (dark-bright pair) interactions, such as elastic and
      inelastic interactions and the dynamics of soliton bound states, are studied
      using asymptotic analysis and graphical analysis. We show that a bright 2
      soliton, in addition to elastic interactions, also exhibits multiple inelastic
      interactions. A dark 2-soliton, on the other hand, exhibits only elastic
      interactions. We also observe a breatherlike structure of a bright 2-soliton, a
      feature that become prominent with gain and disappears as the amplitude acquires
      a minimum value, and after that the solitons remain parallel. The dark 2-soliton,
      however, remains parallel irrespective of the gain. The results found by us might
      be useful for applications in soliton control, a fiber amplifier, all optical
      switching, and optical computing. 

PMID- 25768630
TI  - Multipseudopotential interaction: a solution for thermodynamic inconsistency in
      pseudopotential lattice Boltzmann models.
AB  - Pseudopotential lattice Boltzmann (LB) models have been recognized as efficient
      numerical tools to simulate complex fluid systems, including those at
      thermodynamic equilibrium states and with phase transitions. However, when the
      equation of state (EOS) of real fluids is implemented, the existing
      pseudopotential LB models suffer from thermodynamic inconsistency. This study
      presents a multipseudopotential interparticle interaction (MPI) scheme, which is
      fully consistent with thermodynamics and applicable to engineering applications.
      In this framework, multiple pseudopotentials are employed to represent dominant
      interaction potentials at different extents of the mean free path of particles.
      By simulating van der Waals and Carnahan-Starling fluids, it is demonstrated that
      the MPI scheme can correctly simulate the physical nature of two-phase systems on
      the lattice including the continuum predictions of liquid-vapor coexistence
      states and the sound speeds in liquid and vapor phases. It is also shown that the
      lattice interactions of the MPI scheme represent underlying molecular
      interactions as they vary in a broad range from strong short-distance repulsions
      to weak long-distance attractions during phase transitions. Consequently, the MPI
      is proved to be a reliable LB scheme as it avoids generating unphysical
      potentials in implementing the EOSs of real fluids and limiting the spurious
      velocities at the interface of two-phase systems. Additionally, a straightforward
      procedure is suggested and discussed to preset the MPI system with the two-phase
      properties of a selected fluid. 

PMID- 25768631
TI  - Phasing a segmented telescope.
AB  - A crucial part of segmented or multiple-aperture systems is control of the
      optical path difference between the segments or subapertures. In order to achieve
      optimal performance we have to phase subapertures to within a fraction of the
      wavelength, and this requires high accuracy of positioning for each subaperture.
      We present simulations and hardware realization of a simulated annealing
      algorithm in an active optical system with sparse segments. In order to align the
      optical system we applied the optimization algorithm to the image itself. The
      main advantage of this method over traditional correction methods is that wave
      front-sensing hardware and software are no longer required, making the optical
      and mechanical system much simpler. The results of simulations and laboratory
      experiments demonstrate the ability of this optimization algorithm to correct
      both piston and tip-tilt errors. 

PMID- 25768632
TI  - Benchmark values for molecular two-electron integrals arising from the Dirac
      equation.
AB  - The two-center two-electron Coulomb and hybrid integrals arising in relativistic
      and nonrelativistic ab initio calculations on molecules are evaluated. Compact,
      arbitrarily accurate expressions are obtained. They are expressed through
      molecular auxiliary functions and evaluated with the numerical Global-adaptive
      method for arbitrary values of parameters in the noninteger Slater-type orbitals.
      Highly accurate benchmark values are presented for these integrals. The
      convergence properties of new molecular auxiliary functions are investigated. The
      comparison for two-center two-electron integrals is made with results obtained
      from single center expansions by translation of the wave function to a single
      center with integer principal quantum numbers and results obtained from the Cuba
      numerical integration algorithm, respectively. The procedures discussed in this
      work are capable of yielding highly accurate two-center two-electron integrals
      for all ranges of orbital parameters. 

PMID- 25768633
TI  - Lattice Boltzmann formulation for conjugate heat transfer in heterogeneous media.
AB  - In this paper, we propose an approach for studying conjugate heat transfer using
      the lattice Boltzmann method (LBM). The approach is based on reformulating the
      lattice Boltzmann equation for solving the conservative form of the energy
      equation. This leads to the appearance of a source term, which introduces the
      jump conditions at the interface between two phases or components with different
      thermal properties. The proposed source term formulation conserves conductive and
      advective heat flux simultaneously, which makes it suitable for modeling
      conjugate heat transfer in general multiphase or multicomponent systems. The
      simple implementation of the source term approach avoids any correction of
      distribution functions neighboring the interface and provides an algorithm that
      is independent from the topology of the interface. Moreover, our approach is
      independent of the choice of lattice discretization and can be easily applied to
      different advection-diffusion LBM solvers. The model is tested against several
      benchmark problems including steady-state convection-diffusion within two fluid
      layers with parallel and normal interfaces with respect to the flow direction,
      unsteady conduction in a three-layer stratified domain, and steady conduction in
      a two-layer annulus. The LBM results are in excellent agreement with analytical
      solution. Error analysis shows that our model is first-order accurate in space,
      but an extension to a second-order scheme is straightforward. We apply our LBM
      model to heat transfer in a two-component heterogeneous medium with a random
      microstructure. This example highlights that the method we propose is independent
      of the topology of interfaces between the different phases and, as such, is
      ideally suited for complex natural heterogeneous media. We further validate the
      present LBM formulation with a study of natural convection in a porous enclosure.
      The results confirm the reliability of the model in simulating complex coupled
      fluid and thermal dynamics in complex geometries. 

PMID- 25768634
TI  - Improved forcing scheme in pseudopotential lattice Boltzmann methods for
      multiphase flow at arbitrarily high density ratios.
AB  - The pseudopotential lattice Boltzmann method has been widely used to simulate
      many multiphase flow applications. However, there still exist problems with
      reproducing realistic values of density ratio and surface tension. In this study,
      a higher-order analysis of a general forcing term is derived. A forcing scheme is
      then constructed for the pseudopotential method that is able to accurately
      reproduce the full range of coexistence curves. As a result, multiphase flow of
      arbitrarily high density ratios independent of the surface tension can be
      simulated. Furthermore, the interface width can be tuned to allow for grid
      refinement and systematic error reduction. Numerical results confirm that the
      proposed scheme enables independent control of density ratio, surface tension,
      and interface width simultaneously. 

PMID- 25768635
TI  - Analysis of the phase transition in the two-dimensional Ising ferromagnet using a
      Lempel-Ziv string-parsing scheme and black-box data-compression utilities.
AB  - In this work we consider information-theoretic observables to analyze short
      symbolic sequences, comprising time series that represent the orientation of a
      single spin in a two-dimensional (2D) Ising ferromagnet on a square lattice of
      size L(2)=128(2) for different system temperatures T. The latter were chosen from
      an interval enclosing the critical point T(c) of the model. At small temperatures
      the sequences are thus very regular; at high temperatures they are maximally
      random. In the vicinity of the critical point, nontrivial, long-range
      correlations appear. Here we implement estimators for the entropy rate, excess
      entropy (i.e., "complexity"), and multi-information. First, we implement a Lempel
      Ziv string-parsing scheme, providing seemingly elaborate entropy rate and multi
      information estimates and an approximate estimator for the excess entropy.
      Furthermore, we apply easy-to-use black-box data-compression utilities, providing
      approximate estimators only. For comparison and to yield results for benchmarking
      purposes, we implement the information-theoretic observables also based on the
      well-established M-block Shannon entropy, which is more tedious to apply compared
      to the first two "algorithmic" entropy estimation procedures. To test how well
      one can exploit the potential of such data-compression techniques, we aim at
      detecting the critical point of the 2D Ising ferromagnet. Among the above
      observables, the multi-information, which is known to exhibit an isolated peak at
      the critical point, is very easy to replicate by means of both efficient
      algorithmic entropy estimation procedures. Finally, we assess how good the
      various algorithmic entropy estimates compare to the more conventional block
      entropy estimates and illustrate a simple modification that yields enhanced
      results.

PMID- 25768636
TI  - Analysis and improvement of Brinkman lattice Boltzmann schemes: bulk, boundary,
      interface. Similarity and distinctness with finite elements in heterogeneous
      porous media.
AB  - This work focuses on the numerical solution of the Stokes-Brinkman equation for a
      voxel-type porous-media grid, resolved by one to eight spacings per permeability
      contrast of 1 to 10 orders in magnitude. It is first analytically demonstrated
      that the lattice Boltzmann method (LBM) and the linear-finite-element method
      (FEM) both suffer from the viscosity correction induced by the linear variation
      of the resistance with the velocity. This numerical artefact may lead to an
      apparent negative viscosity in low-permeable blocks, inducing spurious velocity
      oscillations. The two-relaxation-times (TRT) LBM may control this effect thanks
      to free-tunable two-rates combination Lambda. Moreover, the Brinkman-force-based
      BF-TRT schemes may maintain the nondimensional Darcy group and produce viscosity
      independent permeability provided that the spatial distribution of Lambda is
      fixed independently of the kinematic viscosity. Such a property is lost not only
      in the BF-BGK scheme but also by "partial bounce-back" TRT gray models, as shown
      in this work. Further, we propose a consistent and improved IBF-TRT model which
      vanishes viscosity correction via simple specific adjusting of the viscous-mode
      relaxation rate to local permeability value. This prevents the model from
      velocity fluctuations and, in parallel, improves for effective permeability
      measurements, from porous channel to multidimensions. The framework of our exact
      analysis employs a symbolic approach developed for both LBM and FEM in single and
      stratified, unconfined, and bounded channels. It shows that even with similar
      bulk discretization, BF, IBF, and FEM may manifest quite different velocity
      profiles on the coarse grids due to their intrinsic contrasts in the setting of
      interface continuity and no-slip conditions. While FEM enforces them on the grid
      vertexes, the LBM prescribes them implicitly. We derive effective LBM continuity
      conditions and show that the heterogeneous viscosity correction impacts them, a
      property also shared by FEM for shear stress. But, in contrast with FEM,
      effective velocity conditions in LBM give rise to slip velocity jumps which
      depend on (i) neighbor permeability values, (ii) resolution, and (iii) control
      parameter Lambda, ranging its reliable values from Poiseuille bounce-back
      solution in open flow to zero in Darcy's limit. We suggest an "upscaling"
      algorithm for Lambda, from multilayers to multidimensions in random extremely
      dispersive samples. Finally, on the positive side for LBM besides its overall
      versatility, the implicit boundary layers allow for smooth accommodation of the
      flat discontinuous Darcy profiles, quite deficient in FEM. 

PMID- 25768637
TI  - Free energies of molecular clusters determined by guided mechanical disassembly.
AB  - The excess free energy of a molecular cluster is a key quantity in models of the
      nucleation of droplets from a metastable vapor phase; it is often viewed as the
      free energy arising from the presence of an interface between the two phases. We
      show how this quantity can be extracted from simulations of the mechanical
      disassembly of a cluster using guide particles in molecular dynamics. We
      disassemble clusters ranging in size from 5 to 27 argonlike Lennard-Jones atoms,
      thermalized at 60 K, and obtain excess free energies, by means of the Jarzynski
      equality, that are consistent with previous studies. We only simulate the cluster
      of interest, in contrast to approaches that require a series of comparisons to be
      made between clusters differing in size by one molecule. We discuss the
      advantages and disadvantages of the scheme and how it might be applied to more
      complex systems. 

PMID- 25768638
TI  - Meshless lattice Boltzmann method for the simulation of fluid flows.
AB  - A meshless lattice Boltzmann numerical method is proposed. The collision and
      streaming operators of the lattice Boltzmann equation are separated, as in the
      usual lattice Boltzmann models. While the purely local collision equation remains
      the same, we rewrite the streaming equation as a pure advection equation and
      discretize the resulting partial differential equation using the Lax-Wendroff
      scheme in time and the meshless local Petrov-Galerkin scheme based on augmented
      radial basis functions in space. The meshless feature of the proposed method
      makes it a more powerful lattice Boltzmann solver, especially for cases in which
      using meshes introduces significant numerical errors into the solution, or when
      improving the mesh quality is a complex and time-consuming process. Three well
      known benchmark fluid flow problems, namely the plane Couette flow, the circular
      Couette flow, and the impulsively started cylinder flow, are simulated for the
      validation of the proposed method. Excellent agreement with analytical solutions
      or with previous experimental and numerical results in the literature is observed
      in all the simulations. Although the computational resources required for the
      meshless method per node are higher compared to that of the standard lattice
      Boltzmann method, it is shown that for cases in which the total number of nodes
      is significantly reduced, the present method actually outperforms the standard
      lattice Boltzmann method. 

PMID- 25768639
TI  - Detecting vortices in superconductors: extracting one-dimensional topological
      singularities from a discretized complex scalar field.
AB  - In type II superconductors, the dynamics of superconducting vortices determine
      their transport properties. In the Ginzburg-Landau theory, vortices correspond to
      topological defects in the complex order parameter. Extracting their precise
      positions and motion from discretized numerical simulation data is an important,
      but challenging, task. In the past, vortices have mostly been detected by
      analyzing the magnitude of the complex scalar field representing the order
      parameter and visualized by corresponding contour plots and isosurfaces. However,
      these methods, primarily used for small-scale simulations, blur the fine details
      of the vortices, scale poorly to large-scale simulations, and do not easily
      enable isolating and tracking individual vortices. Here we present a method for
      exactly finding the vortex core lines from a complex order parameter field. With
      this method, vortices can be easily described at a resolution even finer than the
      mesh itself. The precise determination of the vortex cores allows the interplay
      of the vortices inside a model superconductor to be visualized in higher
      resolution than has previously been possible. By representing the field as the
      set of vortices, this method also massively reduces the data footprint of the
      simulations and provides the data structures for further analysis and feature
      tracking. 

PMID- 25768640
TI  - Reaction rates for mesoscopic reaction-diffusion kinetics.
AB  - The mesoscopic reaction-diffusion master equation (RDME) is a popular modeling
      framework frequently applied to stochastic reaction-diffusion kinetics in systems
      biology. The RDME is derived from assumptions about the underlying physical
      properties of the system, and it may produce unphysical results for models where
      those assumptions fail. In that case, other more comprehensive models are better
      suited, such as hard-sphere Brownian dynamics (BD). Although the RDME is a model
      in its own right, and not inferred from any specific microscale model, it proves
      useful to attempt to approximate a microscale model by a specific choice of
      mesoscopic reaction rates. In this paper we derive mesoscopic scale-dependent
      reaction rates by matching certain statistics of the RDME solution to statistics
      of the solution of a widely used microscopic BD model: the Smoluchowski model
      with a Robin boundary condition at the reaction radius of two molecules. We also
      establish fundamental limits on the range of mesh resolutions for which this
      approach yields accurate results and show both theoretically and in numerical
      examples that as we approach the lower fundamental limit, the mesoscopic dynamics
      approach the microscopic dynamics. We show that for mesh sizes below the
      fundamental lower limit, results are less accurate. Thus, the lower limit
      determines the mesh size for which we obtain the most accurate results. 

PMID- 25768641
TI  - Fluctuating multicomponent lattice Boltzmann model.
AB  - Current implementations of fluctuating lattice Boltzmann equations (FLBEs)
      describe single component fluids. In this paper, a model based on the continuum
      kinetic Boltzmann equation for describing multicomponent fluids is extended to
      incorporate the effects of thermal fluctuations. The thus obtained fluctuating
      Boltzmann equation is first linearized to apply the theory of linear
      fluctuations, and expressions for the noise covariances are determined by
      invoking the fluctuation-dissipation theorem directly at the kinetic level.
      Crucial for our analysis is the projection of the Boltzmann equation onto the
      orthonormal Hermite basis. By integrating in space and time the fluctuating
      Boltzmann equation with a discrete number of velocities, the FLBE is obtained for
      both ideal and nonideal multicomponent fluids. Numerical simulations are
      specialized to the case where mean-field interactions are introduced on the
      lattice, indicating a proper thermalization of the system. 

PMID- 25768642
TI  - Comment on "Casimir force in the O(n->infinity) model with free boundary
      conditions".
AB  - In a recent paper by D. Dantchev, J. Bergknoff, and J. Rudnick [Phys. Rev. E 89,
      042116 (2014)], the problem of the Casimir force in the O(n) model on a slab with
      free boundary conditions, investigated earlier by us [Europhys. Lett. 100, 10004
      (2012)], is reconsidered using a mean-spherical model with separate constraints
      for each layer. The authors (i) question the applicability of the Ginzburg-Landau
      Wilson approach to the low-temperature regime, arguing for the superiority of
      their model compared to the family of phi(4) models A and B whose numerically
      exact solutions we determined both for values of the coupling constant
      0<g<infinity and for g=infinity. They (ii) report consistency of their results
      with ours in the critical region and a strong manifestation of universality but
      (iii) point out discrepancies with our results in the region below T(c). Here we
      refute (i) and prove that our model B with g=infinity is identical to their
      spherical model. Hence evidence for the reported universality is already
      contained in our paper. Moreover, the results we determined for anyone of the
      models A and B for various thicknesses L are all numerically exact. (iii) is due
      to their misinterpretation of our results for the scaling limit. We also show
      that their low-temperature expansion, which does not hold inside the scaling
      regime, is limited to temperatures lower than they anticipated.

PMID- 25768643
TI  - Reply to "Comment on 'Casimir force in the O(n->infinity) model with free
      boundary conditions' ".
AB  - The preceding Comment raises a few points concerning our paper [Phys. Rev. E 89,
      042116 (2014)]. In this Reply we stress that although Diehl et al. [Europhys.
      Lett. 100, 10004 (2012) and Phys. Rev. E 89, 062123 (2014)] use three different
      models to study the Casimir force for the O(n->infinity) model with free boundary
      conditions we study a single model over the entire range of temperatures from
      above the bulk critical temperature T(c) to absolute temperatures down to T=0.
      The use of a single model renders more transparent the crossover from effects
      dominated by critical fluctuations in the vicinity of the bulk transition
      temperature to effects controlled by Goldstone modes at low temperatures.
      Contrary to the assertion in the Comment, we make no claim for the superiority of
      our model over any of those considered by Diehl et al. [Europhys. Lett. 100,
      10004 (2012) and Phys. Rev. E 89, 062123 (2014)]. We also present additional
      evidence supporting our conclusion in Dantchev et al. [Phys. Rev. E 89, 042116
      (2014)] that the temperature range in which our low-temperature analytical
      expansion for the Casimir force increases as L grows and remains accurate for
      values of the ratio T/T(c) that become closer and closer to unity, whereas T
      remains well outside of the critical region.

PMID- 25768644
TI  - Comment on "Calculations for the one-dimensional soft Coulomb problem and the
      hard Coulomb limit".
AB  - In the referred paper, the authors use a numerical method for solving ordinary
      differential equations and a softened Coulomb potential -1/?[x(2)+beta(2)] to
      study the one-dimensional Coulomb problem by approaching the parameter beta to
      zero. We note that even though their numerical findings in the soft potential
      scenario are correct, their conclusions do not extend to the one-dimensional
      Coulomb problem (beta=0). Their claims regarding the possible existence of an
      even ground state with energy -infinity with a Dirac-delta eigenfunction and of
      well-defined parity eigenfunctions in the one-dimensional hydrogen atom are
      questioned.

PMID- 25768645
TI  - Reply to "Comment on 'Calculations for the one-dimensional soft Coulomb problem
      and the hard Coulomb limit' ".
AB  - This is a response to the comment we received on our recent paper "Calculations
      for the one-dimensional soft Coulomb problem and the hard Coulomb limit." In that
      paper, we introduced a computational algorithm that is appropriate for solving
      stiff initial value problems, and which we applied to the one-dimensional time
      independent Schrodinger equation with a soft Coulomb potential. We solved for the
      eigenpairs using a shooting method and hence turned it into an initial value
      problem. In particular, we examined the behavior of the eigenpairs as the
      softening parameter approached zero (hard Coulomb limit). The commenters question
      the existence of the ground state of the hard Coulomb potential, which we
      inferred by extrapolation of the softening parameter to zero. A key distinction
      between the commenters' approach and ours is that they consider only the half
      line while we considered the entire x axis. Based on mathematical considerations,
      the commenters consider only a vanishing solution function at the origin, and
      they question our conclusion that the ground state of the hard Coulomb potential
      exists. The ground state we inferred resembles a delta(x), and hence it cannot
      even be addressed based on their argument. For the excited states, there is
      agreement with the fact that the particle is always excluded from the origin. Our
      discussion with regard to the symmetry of the excited states is an extrapolation
      of the soft Coulomb case and is further explained herein. 

PMID- 25768647
TI  - Controlled translocation of DNA through nanopores in carbon nano-, silicon
      nitride- and lipid-coated membranes.
AB  - We investigated experimentally and theoretically the translocation forces when a
      charged polymer is threaded through a solid-state nanopore and found distinct
      dependencies on the nanopore diameter as well as on the nano membrane material
      chemistry. For this purpose we utilized dedicated optical tweezers force
      mechanics capable of probing the insertion of negatively charged double-stranded
      DNA inside a helium-ion drilled nanopore. We found that both the diameter of the
      nanopore and the membrane material itself have significant influences on the
      electroosmotic flow through the nanopore and thus on the threading force.
      Compared to a bare silicon-nitride membrane, the threading of DNA through only 3
      nm thin carbon nano membranes as well as lipid bilayer-coated nanopores increased
      the threading force by 15% or 85%, respectively. This finding was quantitatively
      described by our recently developed theoretical model that also incorporates
      hydrodynamic slip effects on the translocating DNA molecule and the force
      dependence on the membrane thickness. The additional measurements presented in
      this paper further support our model. 

PMID- 25768646
TI  - Adenovirus entry from the apical surface of polarized epithelia is facilitated by
      the host innate immune response.
AB  - Prevention of viral-induced respiratory disease begins with an understanding of
      the factors that increase or decrease susceptibility to viral infection. The
      primary receptor for most adenoviruses is the coxsackievirus and adenovirus
      receptor (CAR), a cell-cell adhesion protein normally localized at the
      basolateral surface of polarized epithelia and involved in neutrophil
      transepithelial migration. Recently, an alternate isoform of CAR, CAREx8, has
      been identified at the apical surface of polarized airway epithelia and is
      implicated in viral infection from the apical surface. We hypothesized that the
      endogenous role of CAREx8 may be to facilitate host innate immunity. We show that
      IL-8, a proinflammatory cytokine and a neutrophil chemoattractant, stimulates the
      protein expression and apical localization of CAREx8 via activation of AKT/S6K
      and inhibition of GSK3beta. Apical CAREx8 tethers infiltrating neutrophils at the
      apical surface of a polarized epithelium. Moreover, neutrophils present on the
      apical-epithelial surface enhance adenovirus entry into the epithelium. These
      findings suggest that adenovirus evolved to co-opt an innate immune response
      pathway that stimulates the expression of its primary receptor, apical CAREx8, to
      allow the initial infection the intact epithelium. In addition, CAREx8 is a new
      target for the development of novel therapeutics for both respiratory
      inflammatory disease and adenoviral infection. 

PMID- 25768648
TI  - Lipid-free antigen B subunits from echinococcus granulosus: oligomerization,
      ligand binding, and membrane interaction properties.
AB  - BACKGROUND: The hydatid disease parasite Echinococcus granulosus has a restricted
      lipid metabolism, and needs to harvest essential lipids from the host. Antigen B
      (EgAgB), an abundant lipoprotein of the larval stage (hydatid cyst), is thought
      to be important in lipid storage and transport. It contains a wide variety of
      lipid classes, from highly hydrophobic compounds to phospholipids. Its protein
      component belongs to the cestode-specific Hydrophobic Ligand Binding Protein
      family, which includes five 8-kDa isoforms encoded by a multigene family (EgAgB1
      EgAgB5). How lipid and protein components are assembled into EgAgB particles
      remains unknown. EgAgB apolipoproteins self-associate into large oligomers, but
      the functional contribution of lipids to oligomerization is uncertain.
      Furthermore, binding of fatty acids to some EgAgB subunits has been reported, but
      their ability to bind other lipids and transfer them to acceptor membranes has
      not been studied. METHODOLOGY/PRINCIPAL FINDINGS: Lipid-free EgAgB subunits
      obtained by reverse-phase HPLC were used to analyse their oligomerization, ligand
      binding and membrane interaction properties. Size exclusion chromatography and
      cross-linking experiments showed that EgAgB8/2 and EgAgB8/3 can self-associate,
      suggesting that lipids are not required for oligomerization. Furthermore, using
      fluorescent probes, both subunits were found to bind fatty acids, but not
      cholesterol analogues. Analysis of fatty acid transfer to phospholipid vesicles
      demonstrated that EgAgB8/2 and EgAgB8/3 are potentially capable of transferring
      fatty acids to membranes, and that the efficiency of transfer is dependent on the
      surface charge of the vesicles. CONCLUSIONS/SIGNIFICANCE: We show that EgAgB
      apolipoproteins can oligomerize in the absence of lipids, and can bind and
      transfer fatty acids to phospholipid membranes. Since imported fatty acids are
      essential for Echinococcus granulosus, these findings provide a mechanism whereby
      EgAgB could engage in lipid acquisition and/or transport between parasite
      tissues. These results may therefore indicate vulnerabilities open to targeting
      by new types of drugs for hydatidosis therapy.

PMID- 25768649
TI  - Conjugation of the ubiquitin activating enzyme UBE1 with the ubiquitin-like
      modifier FAT10 targets it for proteasomal degradation.
AB  - The ubiquitin-like modifier HLA-F adjacent transcript 10 (FAT10) directly targets
      its substrates for proteasomal degradation by becoming covalently attached via
      its C-terminal diglycine motif to internal lysine residues of its substrate
      proteins. The conjugation machinery consists of the bispecific E1 activating
      enzyme Ubiquitin-like modifier activating enzyme 6 (UBA6), the likewise
      bispecific E2 conjugating enzyme UBA6-specific E2 enzyme 1 (USE1), and possibly
      E3 ligases. By mass spectrometry analysis the ubiquitin E1 activating enzyme
      ubiquitin-activating enzyme 1 (UBE1) was identified as putative substrate of
      FAT10. Here, we confirm that UBE1 and FAT10 form a stable non-reducible conjugate
      under overexpression as well as under endogenous conditions after induction of
      endogenous FAT10 expression with proinflammatory cytokines. FAT10ylation of UBE1
      depends on the diglycine motif of FAT10. By specifically downregulating FAT10,
      UBA6 or USE1 with siRNAs, we show that UBE1 modification depends on the FAT10
      conjugation pathway. Furthermore, we confirm that UBE1 does not act as a second
      E1 activating enzyme for FAT10 but that FAT10ylation of UBE1 leads to its
      proteasomal degradation, implying a putative regulatory role of FAT10 in the
      ubiquitin conjugation pathway. 

PMID- 25768650
TI  - Determination of the optimal training principle and input variables in artificial
      neural network model for the biweekly chlorophyll-a prediction: a case study of
      the Yuqiao Reservoir, China.
AB  - Predicting the levels of chlorophyll-a (Chl-a) is a vital component of water
      quality management, which ensures that urban drinking water is safe from harmful
      algal blooms. This study developed a model to predict Chl-a levels in the Yuqiao
      Reservoir (Tianjin, China) biweekly using water quality and meteorological data
      from 1999-2012. First, six artificial neural networks (ANNs) and two non-ANN
      methods (principal component analysis and the support vector regression model)
      were compared to determine the appropriate training principle. Subsequently,
      three predictors with different input variables were developed to examine the
      feasibility of incorporating meteorological factors into Chl-a prediction, which
      usually only uses water quality data. Finally, a sensitivity analysis was
      performed to examine how the Chl-a predictor reacts to changes in input
      variables. The results were as follows: first, ANN is a powerful predictive
      alternative to the traditional modeling techniques used for Chl-a prediction. The
      back program (BP) model yields slightly better results than all other ANNs, with
      the normalized mean square error (NMSE), the correlation coefficient (Corr), and
      the Nash-Sutcliffe coefficient of efficiency (NSE) at 0.003 mg/l, 0.880 and
      0.754, respectively, in the testing period. Second, the incorporation of
      meteorological data greatly improved Chl-a prediction compared to models solely
      using water quality factors or meteorological data; the correlation coefficient
      increased from 0.574-0.686 to 0.880 when meteorological data were included.
      Finally, the Chl-a predictor is more sensitive to air pressure and pH compared to
      other water quality and meteorological variables. 

PMID- 25768651
TI  - Quantifying BTEX in aqueous solutions with potentially interfering hydrocarbons
      using a partially selective sensor array.
AB  - Partially selective gold nanoparticle sensors have the sensitivity and
      selectivity to discriminate and quantify benzene, toluene, ethylbenzene, p-xylene
      and naphthalene (BTEXN) at concentrations relevant to the US Environmental
      Protection Agency. In this paper we demonstrate that gold nanoparticle
      chemiresistors can do so in the presence of 16 other hydrocarbons and that they
      did not reduce the discriminating power of the array. A two-level full factorial
      designed experiment was performed on unary, binary, ternary, quaternary, quinary
      combinations of BTEXN analytes with and without the possibly interfering
      hydrocarbons. The nominal component concentration of the mixtures was 100 MUg L(
      1), equivalent to approximately 100 parts per billion (ppb). Concentrations
      predicted with the random forests method had an average root mean square error of
      10-20% of the component concentrations. This level of accuracy was achieved
      regardless of whether or not the 16 possibly interfering hydrocarbons were
      present. This work shows that the sensitivity and selectivity of gold
      nanoparticles chemiresistor sensors towards BTEXN analytes are not unduly
      affected by the other hydrocarbons that are expected to be present at a petroleum
      remediation site. 

PMID- 25768652
TI  - Temporal Processing Deficits in Middle Age.
AB  - PURPOSE: The purpose of this brief report is to provide a synopsis of recent
      work, primarily from the authors' laboratory, that points to the emergence of
      temporal processing deficits relatively early in the aging process. METHOD: The
      approach taken was to provide a descriptive summary of selected published and
      current experiments focusing on the processing of temporal envelopes and fine
      structure. CONCLUSION: Deficits in both temporal envelope and temporal fine
      structure processing are evident during middle age even while audiometric hearing
      sensitivity remains normal.

PMID- 25768653
TI  - Synthesis and structural analysis of angular monoprotected diamines based on
      spiro[3.3]heptane scaffold.
AB  - The synthesis of all stereoisomers of spiro[3.3]heptane-1,6-diamines suitably
      protected for use as building blocks in drug discovery is reported. Structural
      analysis revealed the similarity between the spiro[3.3]heptane and cyclohexane
      scaffolds. Comparison of the distance between functional groups and their spatial
      orientation proved that (1S,4r,6R)- and (1R,4r,6S)-1,6-disubstituted
      spiro[3.3]heptanes can be considered as restricted surrogates of cis-1,4
      disubstituted cyclohexane derivatives. Similarly, (1S,4s,6R)- and (1R,4s,6S)-1,6
      disubstituted spiro[3.3]heptanes are the restricted surrogates of trans-1,3
      disubstituted cyclohexanes. Such replacement can be recommended for use in
      optimization of ADME parameters of lead compounds in drug discovery. 

PMID- 25768655
TI  - Design and Synthesis of Bubble-Nanorod-Structured Fe2O3-Carbon Nanofibers as
      Advanced Anode Material for Li-Ion Batteries.
AB  - A structure denoted as a "bubble-nanorod composite" is synthesized by introducing
      the Kirkendall effect into the electrospinning method. Bubble-nanorod-structured
      Fe2O3-C composite nanofibers, which are composed of nanosized hollow Fe2O3
      spheres uniformly dispersed in an amorphous carbon matrix, are synthesized as the
      target material. Post-treatment of the electrospun precursor nanofibers at 500 
      degrees C under 10% H2/Ar mixture gas atmosphere produces amorphous FeOx-carbon
      composite nanofibers. Post-treatment of the FeOx-carbon composite nanofibers at
      300  degrees C under air atmosphere produces the bubble-nanorod-structured Fe2O3
      C composite nanofibers. The solid Fe nanocrystals formed by the reduction of FeOx
      are converted into hollow Fe2O3 nanospheres during the further heating process by
      the well-known Kirkendall diffusion process. The discharge capacities of the
      bubble-nanorod-structured Fe2O3-C composite nanofibers and hollow bare Fe2O3
      nanofibers for the 300th cycles at a current density of 1.0 A g(-1) are 812 and
      285 mA h g(-1), respectively, and their capacity retentions measured from the
      second cycle are 84 and 24%, respectively. The hollow nanospheres accommodate the
      volume change that occurs during cycling. The unique structure of the bubble
      nanorod-structured Fe2O3-C composite nanofibers results in their superior
      electrochemical properties by improving the structural stability during long-term
      cycling. 

PMID- 25768654
TI  - Reproductive isolation of hybrid populations driven by genetic incompatibilities.
AB  - Despite its role in homogenizing populations, hybridization has also been
      proposed as a means to generate new species. The conceptual basis for this idea
      is that hybridization can result in novel phenotypes through recombination
      between the parental genomes, allowing a hybrid population to occupy ecological
      niches unavailable to parental species. Here we present an alternative model of
      the evolution of reproductive isolation in hybrid populations that occurs as a
      simple consequence of selection against genetic incompatibilities. Unlike
      previous models of hybrid speciation, our model does not incorporate inbreeding,
      or assume that hybrids have an ecological or reproductive fitness advantage
      relative to parental populations. We show that reproductive isolation between
      hybrids and parental species can evolve frequently and rapidly under this model,
      even in the presence of substantial ongoing immigration from parental species and
      strong selection against hybrids. An interesting prediction of our model is that
      replicate hybrid populations formed from the same pair of parental species can
      evolve reproductive isolation from each other. This non-adaptive process can
      therefore generate patterns of species diversity and relatedness that resemble an
      adaptive radiation. Intriguingly, several known hybrid species exhibit patterns
      of reproductive isolation consistent with the predictions of our model. 

PMID- 25768656
TI  - 7-glutathione pyrrole adduct: a potential DNA reactive metabolite of
      pyrrolizidine alkaloids.
AB  - Pyrrolizidine alkaloid (PA)-containing plants are the most common poisonous
      plants affecting livestock, wildlife, and humans. PAs require metabolic
      activation to form pyrrolic metabolites to exert cytotoxicity and tumorigenicity.
      We previously determined that metabolism of tumorigenic PAs produced four DNA
      adducts, designated as DHP-dG-3, DHP-dG-4, DHP-dA-3, and DHP-dA-4, that are
      responsible for liver tumor initiation. 7-Glutathione-(+/-)-6,7-dihydro-1
      hydroxymethyl-5H-pyrrolizine (7-GS-DHP), formed in vivo and in vitro, and 7,9-di
      GS-DHP, formed in vitro, are both considered detoxified metabolites. However, in
      this study we determined that incubation of 7-GS-DHP with 2'-deoxyguanosine (dG)
      and 2'-deoxyadenosine (dA) yields DHP-dG-3, DHP-dG-4, DHP-dA-3, and DHP-dA-4
      adducts as well as the reactive metabolite DHP. Furthermore, reaction of 7-GS-DHP
      with calf thymus DNA in aqueous solution at 37  degrees C for 4, 8, 16, 24, 48,
      or 72 h, followed by enzymatic hydrolysis yielded DHP-dG-3, DHP-dG-4, DHP-dA-3,
      and DHP-dA-4 adducts. Under our current experimental conditions, DHP-dA-3 and DHP
      dA-4 adducts were formed in a trace amount from the reaction of 7,9-di-GS-DHP
      with dA. No DHP-dG-3 or DHP-dG-4 adducts were detected from the reaction of 7,9
      di-GS-DHP with dG. This study represents the first report that the 7-GS-DHP
      adduct can be a potential reactive metabolite of PAs leading to DNA adduct
      formation. 

PMID- 25768657
TI  - Extending the short and long wavelength limits of bacteriochlorin near-infrared
      absorption via dioxo- and bisimide-functionalization.
AB  - Six new bacteriochlorins expanding the range of the strong near-infrared (NIR)
      absorption (Qy band) to both shorter and longer wavelengths (~690 to ~900 nm)
      have been synthesized and characterized. The architectures include
      bacteriochlorin-bisimides that have six-membered imide rings spanning the 3,5-
      and 13,15-macrocycle positions or five-membered imide rings spanning the beta
      pyrrolic 2,3- and 12,13-positions. Both bisimide types absorb at significantly
      longer wavelength than the bacteriochlorin precursors (no fused rings), whereas
      oxo-groups at the 7- or 7,17-positions shift the Qy band to a new short
      wavelength limit. Surprisingly, bacteriochlorin-bisimides with five-membered beta
      pyrrolic-centered imide rings have a Qy band closer to that of six-membered
      bacteriochlorin-monoimides. However, the five-membered bisimides (versus the six
      membered bacteriochlorin-monoimides) have significantly enhanced absorption
      intensity that is paralleled by an ~2-fold higher fluorescence yield (~0.16 vs
      ~0.07) and longer singlet excited-state lifetime (~4 ns vs ~2 ns). The
      photophysical enhancements derive in part from mixing of the lowest unoccupied
      frontier molecular orbitals of the five-membered imide ring with those of the
      bacteriochlorin framework. In general, all of the new bacteriochlorins have
      excited-state lifetimes (1-4 ns) that are sufficiently long for use in molecular
      based systems for photochemical applications. 

PMID- 25768658
TI  - Correction: preferential duplication of intermodular hub genes: an evolutionary
      signature in eukaryotes genome networks.

PMID- 25768659
TI  - Accessibility and vulnerabilty: ensuring security of data in telemedicine.

PMID- 25768660
TI  - Comparing bioenergy production sites in the Southeastern US regarding ecosystem
      service supply and demand.
AB  - Biomass for bioenergy is debated for its potential synergies or tradeoffs with
      other provisioning and regulating ecosystem services (ESS). This biomass may
      originate from different production systems and may be purposefully grown or
      obtained from residues. Increased concerns globally about the sustainable
      production of biomass for bioenergy has resulted in numerous certification
      schemes focusing on best management practices, mostly operating at the plot/field
      scale. In this study, we compare the ESS of two watersheds in the southeastern
      US. We show the ESS tradeoffs and synergies of plantation forestry, i.e., pine
      poles, and agricultural production, i.e., wheat straw and corn stover, with the
      counterfactual natural or semi-natural forest in both watersheds. The plantation
      forestry showed less distinct tradeoffs than did corn and wheat production, i.e.,
      for carbon storage, P and sediment retention, groundwater recharge, and
      biodiversity. Using indicators of landscape composition and configuration, we
      showed that landscape planning can affect the overall ESS supply and can partly
      determine if locally set environmental thresholds are being met. Indicators on
      landscape composition, configuration and naturalness explained more than 30% of
      the variation in ESS supply. Landscape elements such as largely connected forest
      patches or more complex agricultural patches, e.g., mosaics with shrub and
      grassland patches, may enhance ESS supply in both of the bioenergy production
      systems. If tradeoffs between biomass production and other ESS are not addressed
      by landscape planning, it may be reasonable to include rules in certification
      schemes that require, e.g., the connectivity of natural or semi-natural forest
      patches in plantation forestry or semi-natural landscape elements in agricultural
      production systems. Integrating indicators on landscape configuration and
      composition into certification schemes is particularly relevant considering that
      certification schemes are governance tools used to ensure comparable
      sustainability standards for biomass produced in countries with variable or
      absent legal frameworks for landscape planning. 

PMID- 25768662
TI  - Is duration of illness really influencing outcome in major psychoses?
AB  - BACKGROUND: An increasing number of studies identifies the duration of illness
      (DI) as an important predictor of outcome in patients affected by major psychoses
      (MP). The aim of the present paper was to revise medical literature about DI and
      its effects on MP, focusing in particular on the relationship between DI and
      outcome with particular reference to treatment response, suicidal risk, cognitive
      impairment and social functioning. METHODS: A search in the main database sources
      has been performed to obtain a comprehensive overview. Studies with different
      methodologies (open and double-blinded) have been included, while papers
      considering other variables such as duration of untreated episode/illness were
      excluded. MP included the diagnoses of schizophrenia, bipolar disorder and major
      depressive disorder. RESULTS: Available data show that DI influences treatment
      response, suicidal risk and loss of social functioning in schizophrenic patients,
      while results are more controversial with regard to cognitive impairment. In
      bipolar disorder, a long DI has been associated with less treatment response,
      more suicidal risk and cognitive impairment, but more data are needed to draw
      definitive conclusions. Finally, studies, regarding DI of illness and its
      predictive value of outcome in major depressive disorder show contradictory
      results. CONCLUSIONS: DI appears a negative outcome factor particularly for
      schizophrenia, while with regard to mood disorders, more data are needed to draw
      definitive sound conclusions.

PMID- 25768661
TI  - Identification of bacteriology and risk factor analysis of asymptomatic bacterial
      colonization in pacemaker replacement patients.
AB  - BACKGROUND: Recent researches revealed that asymptomatic bacterial colonization
      on PMs might be ubiquitous and increase the risk of clinical PM infection. Early
      diagnosis of patients with asymptomatic bacterial colonization could provide
      opportunity for targeted preventive measures. OBJECTIVE: The present study
      explores the incidence of bacterial colonization of generator pockets in
      pacemaker replacement patients without signs of infection, and to analyze risk
      factors for asymptomatic bacterial colonization. METHODS: From June 2011 to
      December 2013, 118 patients underwent pacemaker replacement or upgrade.
      Identification of bacteria was carried out by bacterial culture and 16S rRNA
      sequencing. Clinical risk characteristics were analyzed. RESULTS: The total
      bacterial positive rate was 37.3% (44 cases), and the coagulase-negative
      Staphylococcus aureus detection rate was the highest. Twenty two (18.6%) patients
      had positive bacterial culture results, of which 50% had coagulase-negative
      staphylococcus. The bacterial DNA detection rate was 36.4 % (43 cases). Positive
      bacterial DNA results from pocket tissues and the surface of the devices were
      22.0% and 29.7%, respectively. During follow-up (median, 27.0 months), three
      patients (6.8%, 3/44) became symptomatic with the same genus of microorganism, S.
      aureus (n=2) and S. epidermidis (n=1). Multivariable logistic regression analysis
      showed that history of bacterial infection, use of antibiotics, application of
      antiplatelet drugs, replacement frequency were independent risk factors for
      asymptomatic bacterial colonization. CONCLUSION: There was a high incidence of
      asymptomatic bacterial colonization in pacemaker patients with independent risk
      factors. Bacterial culture combined genetic testing could improve the detection
      rate.

PMID- 25768663
TI  - The association between interpersonal problems and treatment outcome in the
      eating disorders: A systematic review.
AB  - OBJECTIVE: To review systematically the eating disorder literature in order to
      examine the association between pre-treatment interpersonal problems and
      treatment outcome in people diagnosed with an eating disorder. METHODS: Six
      relevant databases were searched for studies in which interpersonal problems
      prior to treatment were examined in relation to treatment outcome in patients
      diagnosed with anorexia nervosa (AN), bulimia nervosa (BN) or eating disorders
      not otherwise specified (EDNOS). RESULTS: Thirteen studies were identified
      (containing 764 AN, 707 BN and 48 EDNOS). The majority of studies indicated that
      interpersonal problems at the start of therapy were associated with a detrimental
      treatment outcome. CONCLUSIONS: Individuals with a binge/purge-type of eating
      disorder may be particularly vulnerable to interpersonal issues and these issues
      may lead to poorer treatment recovery by reducing the individual's ability to
      engage in the treatment process on a functional level. The clinical and research
      implications are discussed.

PMID- 25768664
TI  - Effects of home telemonitoring interventions on patients with chronic heart
      failure: an overview of systematic reviews.
AB  - BACKGROUND: Growing interest on the effects of home telemonitoring on patients
      with chronic heart failure (HF) has led to a rise in the number of systematic
      reviews addressing the same or very similar research questions with a concomitant
      increase in discordant findings. Differences in the scope, methods of analysis,
      and methodological quality of systematic reviews can cause great confusion and
      make it difficult for policy makers and clinicians to access and interpret the
      available evidence and for researchers to know where knowledge gaps in the extant
      literature exist. OBJECTIVE: This overview aims to collect, appraise, and
      synthesize existing evidence from multiple systematic reviews on the
      effectiveness of home telemonitoring interventions for patients with chronic
      heart failure (HF) to inform policy makers, practitioners, and researchers.
      METHODS: A comprehensive literature search was performed on MEDLINE, EMBASE,
      CINAHL, and the Cochrane Library to identify all relevant, peer-reviewed
      systematic reviews published between January 1996 and December 2013. Reviews were
      searched and screened using explicit keywords and inclusion criteria.
      Standardized forms were used to extract data and the methodological quality of
      included reviews was appraised using the AMSTAR (assessing methodological quality
      of systematic reviews) instrument. Summary of findings tables were constructed
      for all primary outcomes of interest, and quality of evidence was graded by
      outcome using the GRADE (Grades of Recommendation, Assessment, Development, and
      Evaluation) system. Post-hoc analysis and subgroup meta-analyses were conducted
      to gain further insights into the various types of home telemonitoring
      technologies included in the systematic reviews and the impact of these
      technologies on clinical outcomes. RESULTS: A total of 15 reviews published
      between 2003 and 2013 were selected for meta-level synthesis. Evidence from high
      quality reviews with meta-analysis indicated that taken collectively, home
      telemonitoring interventions reduce the relative risk of all-cause mortality
      (0.60 to 0.85) and heart failure-related hospitalizations (0.64 to 0.86) compared
      with usual care. Absolute risk reductions ranged from 1.4%-6.5% and 3.7%-8.2%,
      respectively. Improvements in HF-related hospitalizations appeared to be more
      pronounced in patients with stable HF: hazard ratio (HR) 0.70 (95% credible
      interval [Crl] 0.34-1.5]). Risk reductions in mortality and all-cause
      hospitalizations appeared to be greater in patients who had been recently
      discharged (<=28 days) from an acute care setting after a recent HF exacerbation:
      HR 0.62 (95% CrI 0.42-0.89) and HR 0.67 (95% CrI 0.42-0.97), respectively.
      However, quality of evidence for these outcomes ranged from moderate to low
      suggesting that further research is very likely to have an important impact on
      our confidence in the observed estimates of effect and may change these
      estimates. The post-hoc analysis identified five main types of non-invasive
      telemonitoring technologies included in the systematic reviews: (1) video
      consultation, with or without transmission of vital signs, (2) mobile
      telemonitoring, (3) automated device-based telemonitoring, (4) interactive voice
      response, and (5) Web-based telemonitoring. Of these, only automated device-based
      telemonitoring and mobile telemonitoring were effective in reducing the risk of
      all-cause mortality and HF-related hospitalizations. More research data are
      required for interactive voice response systems, video-consultation, and Web
      based telemonitoring to provide robust conclusions about their effectiveness.
      CONCLUSIONS: Future research should focus on understanding the process by which
      home telemonitoring works in terms of improving outcomes, identify optimal
      strategies and the duration of follow-up for which it confers benefits, and
      further investigate whether there is differential effectiveness between chronic
      HF patient groups and types of home telemonitoring technologies.

PMID- 25768666
TI  - Correction: the nuclear receptor NR4A1 induces a form of cell death dependent on
      autophagy in mammalian cells.

PMID- 25768667
TI  - Odontoid pseudotumor and serial postfusion radiographic evaluation in a patient
      with a C1-2 mass.
AB  - Odontoid pseudotumor is a mass occurring around the odontoid process in the
      cervical spine and can cause significant neurological symptoms at the
      craniocervical junction due to compression of the spinal cord and
      cervicomedullary junction at this level. A literature review was performed to
      provide input on options for treatment and prognosis for this lesion. The
      literature search found 12 papers in which pseudotumor was treated with posterior
      decompression and fixation. Posterior decompression and fixation with serial
      imaging to monitor the size of the pseudotumor postsurgery is a safe and
      effective treatment option for odontoid pseudotumors. 

PMID- 25768665
TI  - Enrofloxacin and macrolides alone or in combination with rifampicin as
      antimicrobial treatment in a bovine model of acute Chlamydia psittaci infection.
AB  - Chlamydia psittaci is a zoonotic bacterium with a wide host range that can cause
      respiratory disease in humans and cattle. In the present study, effects of
      treatment with macrolides and quinolones applied alone or in combination with
      rifampicin were tested in a previously established bovine model of respiratory C.
      psittaci infection. Fifty animals were inoculated intrabronchially at the age of
      6-8 weeks. Seven served as untreated controls, the others were assigned to seven
      treatment groups: (i) rifampicin, (ii) enrofloxacin, (iii) enrofloxacin +
      rifampicin, (iv) azithromycin, (v) azithromycin + rifampicin, (vi) erythromycin,
      and (vii) erythromycin + rifampicin. Treatment started 30 hours after inoculation
      and continued until 14 days after inoculation (dpi), when all animals were
      necropsied. The infection was successful in all animals and sufficient antibiotic
      levels were detected in blood plasma and tissue of the treated animals.
      Reisolation of the pathogen was achieved more often from untreated animals than
      from other groups. Nevertheless, pathogen detection by PCR was possible to the
      same extent in all animals and there were no significant differences between
      treated and untreated animals in terms of local (i.e., cell count and
      differentiation of BALF-cells) and systemic inflammation (i.e. white blood cells
      and concentration of acute phase protein LBP), clinical signs, and pathological
      findings at necropsy. Regardless of the reduced reisolation rate in treated
      animals, the treatment of experimentally induced respiratory C. psittaci
      infection with enrofloxacin, azithromycin or erythromycin alone or in combination
      with rifampicin was without obvious benefit for the host, since no significant
      differences in clinical and pathological findings or inflammatory parameters were
      detected and all animals recovered clinically within two weeks.

PMID- 25768668
TI  - Traumatic spondyloptosis: a series of 20 patients.
AB  - OBJECT Spondyloptosis represents the most severe form of spondylolisthesis, which
      usually follows high-energy trauma. Few reports exist on this specific condition,
      and the largest series published to date consists of only 5 patients. In the
      present study the authors report the clinical observations and outcomes in a
      cohort of 20 patients admitted to a regional trauma center for severe injuries
      including spondyloptosis. METHODS The authors performed a retrospective chart
      review of patients admitted with spondyloptosis at their department over a 5-year
      period (March 2008-March 2013). Clinical, radiological, and operative details
      were reviewed for all patients. RESULTS In total, 20 patients with spondyloptosis
      were treated during the period reviewed. The mean age of the patients was 27
      years (range 12-45 years), and 17 patients were male (2 boys and 15 men) and 3
      were women. Fall from height (45%) and road traffic accidents (35%) were the most
      common causes of the spinal injuries. The grading of the American Spinal Injury
      Association (ASIA) was used to assess the severity of spinal cord injury, which
      for all patients was ASIA Grade A at the time of admission. In 11 patients (55%),
      the thoracolumbar junction (T10-L2) was involved in the injury, followed by the
      dorsal region (T1-9) in 7 patients (35%); 1 patient (5%) had lumbar and 1 patient
      (5%) sacral spondyloptosis. In 19 patients (95%), spondyloptosis was treated
      surgically, involving the posterior route in all cases. In 7 patients (37%),
      corpectomy was performed. None of the patients showed improvement in neurological
      deficits. The mean follow-up length was 37.5 months (range 3-60 months), and 5
      patients died in the follow-up period from complications due to formation of
      bedsores (decubitus ulcers). CONCLUSIONS To the authors' best knowledge, this
      study was the largest of its kind on traumatic spondyloptosis. Its results
      illustrate the challenges of treating patients with this condition. Despite
      deformity correction of the spine and early mobilization of patients, traumatic
      spondyloptosis led to high morbidity and mortality rates because the patients
      lacked access to rehabilitation facilities postoperatively. 

PMID- 25768669
TI  - Iodide- and glucose-handling gene expression regulated by sorafenib or
      cabozantinib in papillary thyroid cancer.
AB  - CONTEXT: The aberrant silencing of iodide-handling genes accompanied by up
      regulation of glucose metabolism presents a major challenge for radioiodine
      treatment of papillary thyroid cancer (PTC). OBJECTIVE: This study aimed to
      evaluate the effect of tyrosine kinase inhibitors on iodide-handling and glucose
      handling gene expression in BHP 2-7 cells harboring RET/PTC1 rearrangement. MAIN
      OUTCOME MEASURES: In this in vitro study, the effects of sorafenib or
      cabozantinib on cell growth, cycles, and apoptosis were investigated by cell
      proliferation assay, cell cycle analysis, and Annexin V-FITC apoptosis assay,
      respectively. The effect of both agents on signal transduction pathways was
      evaluated using the Western blot. Quantitative real-time PCR, Western blot,
      immunofluorescence, and radioisotope uptake assays were used to assess iodide
      handling and glucose-handling gene expression. RESULTS: Both compounds inhibited
      cell proliferation in a time-dependent and dose-dependent manner and caused cell
      cycle arrest in the G0/G1 phase. Sorafenib blocked RET, AKT, and ERK1/2
      phosphorylation, whereas cabozantinib blocked RET and AKT phosphorylation. The
      restoration of iodide-handling gene expression and inhibition of glucose
      transporter 1 and 3 expression could be induced by either drug. The robust
      expression of sodium/iodide symporter induced by either agent was confirmed, and
      (125)I uptake was correspondingly enhanced. (18)F-fluorodeoxyglucose accumulation
      was significantly decreased after treatment by either sorafenib or cabozantinib.
      CONCLUSIONS: Sorafenib and cabozantinib had marked effects on cell proliferation,
      cell cycle arrest, and signal transduction pathways in PTC cells harboring
      RET/PTC1 rearrangement. Both agents could be potentially used to enhance the
      expression of iodide-handling genes and inhibit the expression of glucose
      transporter genes.

PMID- 25768670
TI  - Bone material strength as measured by microindentation in vivo is decreased in
      patients with fragility fractures independently of bone mineral density.
AB  - CONTEXT: Bone mineral density (BMD) does not fully capture fracture risk as the
      majority of fractures occur in patients with osteopenia, suggesting that altered
      bone material properties and changes in microarchitecture may contribute to
      fracture risk. OBJECTIVE: This study aimed to evaluate the relationship between
      bone material strength (BMS), measured by microindentation in vivo, and fracture
      in patients with low bone mass. METHODS: BMS was measured in 90 patients (mean
      age, 61.0 y; range, 40.4-85.5 y) with low bone mass with or without a fragility
      fracture. Sixty-three patients had sustained one or more fragility fractures.
      RESULTS: There was a significant negative correlation between age and BMS (r = 
      0.539; P < .001) and with the 10-year fracture probability with and without
      inclusion of femoral neck BMD as calculated by FRAX (r = -0.383; P < .001 and r =
      -0.426; P < .001, respectively). BMS values were lower in patients with a
      fragility fracture compared with nonfracture patients (79.9 +/- 0.6 vs 82.4 +/-
      1.0; P = .032) despite similar BMD. BMS was comparable in patients with a
      fragility fracture whether they had osteopenia or osteoporosis (79.8 +/- 0.8 vs
      78.7 +/- 1.1; P = .456). In patients with osteopenia, BMS was significantly lower
      in fracture patients than in nonfracture patients (80.3 +/- 0.7 vs 83.9 +/- 1.2;
      P = .015). CONCLUSION: These data suggest that patients with fractures have
      altered material properties of bone that are not captured by BMD. Additional
      studies are required to establish the value of BMS in the prediction of fracture
      risk, especially in patients with osteopenia.

PMID- 25768671
TI  - Diagnostic Accuracy of Copeptin in the Differential Diagnosis of the Polyuria
      polydipsia Syndrome: A Prospective Multicenter Study.
AB  - CONTEXT: The polyuria-polydipsia syndrome comprises primary polydipsia (PP) and
      central and nephrogenic diabetes insipidus (DI). Correctly discriminating these
      entities is mandatory, given that inadequate treatment causes serious
      complications. The diagnostic "gold standard" is the water deprivation test with
      assessment of arginine vasopressin (AVP) activity. However, test interpretation
      and AVP measurement are challenging. OBJECTIVE: The objective was to evaluate the
      accuracy of copeptin, a stable peptide stoichiometrically cosecreted with AVP, in
      the differential diagnosis of polyuria-polydipsia syndrome. DESIGN, SETTING, AND
      PATIENTS: This was a prospective multicenter observational cohort study from four
      Swiss or German tertiary referral centers of adults >18 years old with the
      history of polyuria and polydipsia. MEASUREMENTS: A standardized combined water
      deprivation/3% saline infusion test was performed and terminated when serum
      sodium exceeded 147 mmol/L. Circulating copeptin and AVP levels were measured
      regularly throughout the test. Final diagnosis was based on the water
      deprivation/saline infusion test results, clinical information, and the treatment
      response. RESULTS: Fifty-five patients were enrolled (11 with complete central
      DI, 16 with partial central DI, 18 with PP, and 10 with nephrogenic DI). Without
      prior thirsting, a single baseline copeptin level >21.4 pmol/L differentiated
      nephrogenic DI from other etiologies with a 100% sensitivity and specificity,
      rendering a water deprivation testing unnecessary in such cases. A stimulated
      copeptin >4.9 pmol/L (at sodium levels >147 mmol/L) differentiated between
      patients with PP and patients with partial central DI with a 94.0% specificity
      and a 94.4% sensitivity. A stimulated AVP >1.8 pg/mL differentiated between the
      same categories with a 93.0% specificity and a 83.0% sensitivity. LIMITATION:
      This study was limited by incorporation bias from including AVP levels as a
      diagnostic criterion. CONCLUSION: Copeptin is a promising new tool in the
      differential diagnosis of the polyuria-polydipsia syndrome, and a valid surrogate
      marker for AVP. Primary Funding Sources: Swiss National Science Foundation,
      University of Basel.

PMID- 25768672
TI  - Quiet Submillimeter MR Imaging of the Lung Is Feasible with a PETRA Sequence at
      1.5 T.
AB  - PURPOSE: To assess lung magnetic resonance (MR) imaging with a respiratory-gated
      pointwise encoding time reduction with radial acquisition (PETRA) sequence at 1.5
      T and compare it with imaging with a standard volumetric interpolated breath-hold
      examination (VIBE) sequence, with extra focus on the visibility of bronchi and
      the signal intensity of lung parenchyma. MATERIALS AND METHODS: The study was
      approved by the local ethics committee, and all subjects gave written informed
      consent. Twelve healthy volunteers were imaged with PETRA and VIBE sequences.
      Image quality was evaluated by using visual scoring, numbering of visible
      bronchi, and quantitative measurement of the apparent contrast-to-noise ratio
      (CNR) and signal-to-noise ratio (SNR). For preliminary clinical assessment, three
      young patients with cystic fibrosis underwent both MR imaging and computed
      tomography (CT). Comparisons were made by using the Wilcoxon signed-rank test for
      means and the McNemar test for ratios. Agreement between CT and MR imaging
      disease scores was assessed by using the kappa test. RESULTS: PETRA imaging was
      performed with a voxel size of 0.86 mm(3). Overall image quality was good, with
      little motion artifact. Bronchi were visible consistently up to the fourth
      generation and in some cases up to the sixth generation. Mean CNR and SNR with
      PETRA were 32.4% +/- 7.6 (standard deviation) and 322.2% +/- 37.9, respectively,
      higher than those with VIBE (P < .001). Good agreement was found between CT and
      PETRA cystic fibrosis scores (kappa = 1.0). CONCLUSION: PETRA enables silent,
      free-breathing, isotropic, and submillimeter imaging of the bronchi and lung
      parenchyma with high CNR and SNR and may be an alternative to CT for patients
      with cystic fibrosis.

PMID- 25768673
TI  - Effect of the Availability of Prior Full-Field Digital Mammography and Digital
      Breast Tomosynthesis Images on the Interpretation of Mammograms.
AB  - PURPOSE: To assess the effect of and interaction between the availability of
      prior images and digital breast tomosynthesis (DBT) images in decisions to recall
      women during mammogram interpretation. MATERIALS AND METHODS: Verbal informed
      consent was obtained for this HIPAA-compliant institutional review board-approved
      protocol. Eight radiologists independently interpreted twice deidentified
      mammograms obtained in 153 women (age range, 37-83 years; mean age, 53.7 years +/
      9.3 [standard deviation]) in a mode by reader by case-balanced fully crossed
      study. Each study consisted of current and prior full-field digital mammography
      (FFDM) images and DBT images that were acquired in our facility between June 2009
      and January 2013. For one reading, sequential ratings were provided by using (a)
      current FFDM images only, (b) current FFDM and DBT images, and (c) current FFDM,
      DBT, and prior FFDM images. The other reading consisted of (a) current FFDM
      images only, (b) current and prior FFDM images, and (c) current FFDM, prior FFDM,
      and DBT images. Fifty verified cancer cases, 60 negative and benign cases
      (clinically not recalled), and 43 benign cases (clinically recalled) were
      included. Recall recommendations and interaction between the effect of prior FFDM
      and DBT images were assessed by using a generalized linear model accounting for
      case and reader variability. RESULTS: Average recall rates in noncancer cases
      were significantly reduced with the addition of prior FFDM images by 34% (145 of
      421) and 32% (106 of 333) without and with DBT images, respectively (P < .001).
      However, this recall reduction was achieved at the cost of a corresponding 7% (23
      of 345) and 4% (14 of 353) reduction in sensitivity (P = .006). In contrast,
      availability of DBT images resulted in a smaller reduction in recall rates (false
      positive interpretations) of 19% (76 of 409) and 26% (71 of 276) without and with
      prior FFDM images, respectively (P = .001). Availability of DBT images resulted
      in 4% (15 of 338) and 8% (25 of 322) increases in sensitivity, respectively (P =
      .007). The effects of the availability of prior FFDM images or DBT images did not
      significantly change regardless of the sequence in presentation (P = .81 and P =
      .47 for specificity and sensitivity, respectively). CONCLUSION: The availability
      of prior FFDM or DBT images is a largely independent contributing factor in
      reducing recall recommendations during mammographic interpretation.

PMID- 25768674
TI  - Brain oxygenation during laparoscopic correction of hypertrophic pyloric
      stenosis.
AB  - BACKGROUND: Concern remains about the safety of carbon dioxide (CO2)
      pneumoperitoneum (PP) in young infants having surgery for pyloric stenosis via
      laparoscopy. Interests here mainly focus on possible jeopardized organ perfusion
      and in particular brain oxygenation with possible adverse neurodevelopmental
      outcomes. The aim of this study was to investigate the intraoperative effects of
      CO2 gas PP on cerebral oxygenation during laparoscopic surgery for hypertrophic
      pyloric stenosis in young infants. PATIENTS AND METHODS: In this single-center
      prospective observational study, we investigated brain oxygenation in 12 young
      infants receiving laparoscopic pyloromyotomy with CO2 PP, with a pressure of 8 mm
      Hg and a flow rate of 5 L/minute. Intraoperative hemodynamic parameters and
      transcranial near-infrared spectroscopy to assess regional cerebral oxygen
      saturation (rScO2) were monitored continuously during the whole procedure.
      Parameters were analyzed in four intervals: before insufflation (T0), during
      (start [T1] and end [T2]), and after cessation (T3) of the CO2 PP. RESULTS: Blood
      pressure and end-tidal CO2 (etCO2) increased during the procedure: mean arterial
      pressure, 35+/-5 mm Hg at T0 to 43+/-9 mm Hg at T2; etCO2, 35+/-4 mm Hg at T0 to
      40+/-3 mm Hg at T3. The rScO2 remained stable throughout the whole anesthetic
      period. In none of the patients did the rScO2 drop below the safety threshold of
      55% (rScO2, 68+/-14% at T0 to 71+/-9% at T3). CONCLUSIONS: Our results indicate
      that a laparoscopic procedure with a CO2 PP of 8 mm Hg can be performed under
      safe anesthetic conditions in the presence of gradually increasing blood pressure
      and etCO2 without altering regional brain oxygenation levels.

PMID- 25768675
TI  - The role of surface-based representations of shape in visual object recognition.
AB  - This study contrasted the role of surfaces and volumetric shape primitives in
      three-dimensional object recognition. Observers (N = 50) matched subsets of
      closed contour fragments, surfaces, or volumetric parts to whole novel objects
      during a whole-part matching task. Three factors were further manipulated: part
      viewpoint (either same or different between component parts and whole objects),
      surface occlusion (comparison parts contained either visible surfaces only, or a
      surface that was fully or partially occluded in the whole object), and target
      distractor similarity. Similarity was varied in terms of systematic variation in
      nonaccidental (NAP) or metric (MP) properties of individual parts. Analysis of
      sensitivity (d') showed a whole-part matching advantage for surface-based parts
      and volumes over closed contour fragments--but no benefit for volumetric parts
      over surfaces. We also found a performance cost in matching volumetric parts to
      wholes when the volumes showed surfaces that were occluded in the whole object.
      The same pattern was found for both same and different viewpoints, and regardless
      of target-distractor similarity. These findings challenge models in which
      recognition is mediated by volumetric part-based shape representations. Instead,
      we argue that the results are consistent with a surface-based model of high-level
      shape representation for recognition.

PMID- 25768676
TI  - In vivo imaging of the inner ear at 7T MRI: image evaluation and comparison with
      3T.
AB  - OBJECTIVE: The implementation of 7T magnetic resonance imaging for human use has
      the potential to further advance spatial resolution beyond that of 3T. This could
      result in potential advantages in the depiction of the membranous structures of
      the inner ear. The inner ear is particularly challenging to visualize at 7T
      because of its anatomic location, which can lead to susceptibility banding
      artifacts and signal loss. STUDY DESIGN: Three healthy volunteers underwent
      magnetic resonance imaging at 3T and 7T scanner. At 7T, a unilateral dielectric
      pad was used for image optimization. Scan duration therefore doubled to a total
      of 15 minutes at 7T. METHODS: The depiction of 10 anatomic parts of the inner ear
      was evaluated by two independent readers using a four-point grading scale.
      RESULTS: The interscalar septum, utricular macula, and the nerve bundles in the
      internal auditory canal were visualized more clearly at 7T. CONCLUSION: Although
      reduction of image artifacts remains challenging, especially at 7T, all
      structures depicted at 3T could be depicted at 7T. Image quality for some
      anatomic structures was superior at 7T. Further improvement of image quality
      could be achieved by developing dedicated surface coils and by technical
      advancement in B1 shimming and dedicated radiofrequency pulses.

PMID- 25768677
TI  - A Comparative Study of Iron Uptake Rates and Mechanisms amongst Marine and Fresh
      Water Cyanobacteria: Prevalence of Reductive Iron Uptake.
AB  - In this contribution, we address the question of iron bioavailability to
      cyanobacteria by measuring Fe uptake rates and probing for a reductive uptake
      pathway in diverse cyanobacterial species. We examined three Fe-substrates:
      dissolved inorganic iron (Fe') and the Fe-siderophores Ferrioxamine B (FOB) and
      FeAerobactin (FeAB). In order to compare across substrates and strains, we
      extracted uptake rate constants (kin = uptake rate/[Fe-substrate]). Fe' was the
      most bioavailable Fe form to cyanobacteria, with kin values higher than those of
      other substrates. When accounting for surface area (SA), all strains acquired Fe'
      at similar rates, as their kin/SA were similar. We also observed homogeneity in
      the uptake of FOB among strains, but with 10,000 times lower kin/SA values than
      Fe'. Uniformity in kin/SA suggests similarity in the mechanism of uptake and
      indeed, all strains were found to employ a reductive step in the uptake of Fe'
      and FOB. In contrast, different uptake pathways were found for FeAB along with
      variations in kin/SA. Our data supports the existence of a common reductive Fe
      uptake pathway amongst cyanobacteria, functioning alone or in addition to
      siderophore-mediated uptake. Cyanobacteria combining both uptake strategies
      benefit from increased flexibility in accessing different Fe-substrates. 

PMID- 25768679
TI  - Potocki-Lupski syndrome in conjunction with bilateral clubfoot.
AB  - Potocki-Lupski syndrome (PTLS) is a rare chromosomal microduplication syndrome
      resulting in multiple congenital abnormalities including developmental delays,
      autistic features, and certain structural anomalies, with cardiovascular being
      the most common. The phenotype of this contiguous gene duplication syndrome is
      quite variable and may include musculoskeletal abnormalities. Given the
      infrequency and novelty of this disorder, full phenotypic characterization of
      PTLS has not yet been fully elucidated. We present a case of severe bilateral
      clubfoot in a patient with PTLS. Diagnosis was made by array-based comparative
      genomic hybridization and confirmed by fluorescence in-situ hybridization.
      Because clubfoot was also present in an apparently unaffected brother, the
      presence of PTLS may have acted as a modifier of the phenotype. This report
      highlights the complex interaction of chromosomal and familial factors that
      contribute to musculoskeletal birth defects. 

PMID- 25768680
TI  - Dynamic pedobarography and radiographic evaluation of surgically treated
      cavovarus foot deformity in children with Charcot-Marie-Tooth disease.
AB  - Pedobarography is a common tool for the evaluation of foot deformity. We describe
      our radiographic and pedobarographic outcomes of surgical treatment of cavovarus
      foot deformity in children with Charcot-Marie-Tooth disease. Nineteen patients
      for a total of 30 feet were included. Preoperative and postoperative dynamic
      pedobarographic measurements were made and analyzed using the five-mask
      technique. Pedobarographic measures showed statistical significance for increased
      contact area and decreased peak forces in most mask areas after surgical
      treatment. Peak pressure and redistribution of varus pressure patterns trended
      toward improvement. We found pedobarographic studies helpful; however,
      pedobarographic data are somewhat difficult to interpret and should be used in
      addition to clinical and radiographic examination. 

PMID- 25768678
TI  - Angiogenic activity of breast cancer patients' monocytes reverted by combined use
      of systems modeling and experimental approaches.
AB  - Angiogenesis plays a key role in tumor growth and cancer progression. TIE-2
      expressing monocytes (TEM) have been reported to critically account for tumor
      vascularization and growth in mouse tumor experimental models, but the molecular
      basis of their pro-angiogenic activity are largely unknown. Moreover, differences
      in the pro-angiogenic activity between blood circulating and tumor infiltrated
      TEM in human patients has not been established to date, hindering the
      identification of specific targets for therapeutic intervention. In this work, we
      investigated these differences and the phenotypic reversal of breast tumor pro
      angiogenic TEM to a weak pro-angiogenic phenotype by combining Boolean modelling
      and experimental approaches. Firstly, we show that in breast cancer patients the
      pro-angiogenic activity of TEM increased drastically from blood to tumor,
      suggesting that the tumor microenvironment shapes the highly pro-angiogenic
      phenotype of TEM. Secondly, we predicted in silico all minimal perturbations
      transitioning the highly pro-angiogenic phenotype of tumor TEM to the weak pro
      angiogenic phenotype of blood TEM and vice versa. In silico predicted
      perturbations were validated experimentally using patient TEM. In addition, gene
      expression profiling of TEM transitioned to a weak pro-angiogenic phenotype
      confirmed that TEM are plastic cells and can be reverted to immunological potent
      monocytes. Finally, the relapse-free survival analysis showed a statistically
      significant difference between patients with tumors with high and low expression
      values for genes encoding transitioning proteins detected in silico and validated
      on patient TEM. In conclusion, the inferred TEM regulatory network accurately
      captured experimental TEM behavior and highlighted crosstalk between specific
      angiogenic and inflammatory signaling pathways of outstanding importance to
      control their pro-angiogenic activity. Results showed the successful in vitro
      reversion of such an activity by perturbation of in silico predicted target genes
      in tumor derived TEM, and indicated that targeting tumor TEM plasticity may
      constitute a novel valid therapeutic strategy in breast cancer. 

PMID- 25768681
TI  - Neutrophil gelatinase-associated lipocalin combined with delta serum creatinine
      provides early risk stratification for adverse outcomes after cardiac surgery: a
      prospective observational study.
AB  - OBJECTIVES: Novel biomarkers of renal injury appear inconsistent in identifying a
      creatinine-based diagnosis of acute kidney injury. To be clinically useful, novel
      acute kidney injury biomarkers should identify patients at increased risk for
      adverse outcomes that are a consequence of acute kidney injury earlier and with
      greater utility than conventional creatinine-based metrics. We sought to
      determine the prognostic utility of both urinary neutrophil gelatinase-associated
      lipocalin and varying creatinine-based metrics of renal injury at multiple time
      points associated with cardiac surgery. DESIGN: Prospective observational study.
      SETTING: Academic medical center. PATIENTS: Six hundred three adults undergoing
      cardiac surgery. INTERVENTIONS: Nil. MEASUREMENTS AND MAIN RESULTS: Urinary
      neutrophil gelatinase-associated lipocalin was measured at baseline and again
      less than 1 hour, 3 hours, and 18-24 hours after separation from cardiopulmonary
      bypass. Creatinine-based metrics included a Kidney Disease: Improving Global
      Outcomes definition of acute kidney injury through 7 days postoperatively as well
      as DeltaSCr-initial, defined as the incremental change in SCr from baseline to
      first postoperative measure. Multivariable regression determined the prognostic
      utility of neutrophil gelatinase-associated lipocalin and creatinine, alone and
      in combination, for the primary composite outcome of hospital mortality or renal
      replacement therapy. The primary outcome occurred in 25 patients. Adjusted for
      covariates DeltaSCr-initial greater than or equal to 0.0 mg/dL provided early
      prognostic utility for the primary outcome (odds ratio, 8.9; 95% CI, 3.0-26.6),
      the odds ratio comparable to a creatinine-based Kidney Disease: Improving Global
      Outcomes definition of acute kidney injury applied over 7 days postoperatively.
      The upper quartile of urinary neutrophil gelatinase-associated lipocalin best
      predicted the primary outcome when measured 18-24 hours post-cardiopulmonary
      bypass (odds ratio, 18.6; 95% CI, 5.1-68.4; p = 0.001) with earlier post
      cardiopulmonary bypass measures of uncertain utility. Combining both DeltaSCr
      initial and neutrophil gelatinase-associated lipocalin measured 3 hours after
      cardiopulmonary bypass provided excellent early risk stratification for the
      primary outcome (odds ratio, 18.3; 95% CI, 4.5-75.0). CONCLUSIONS: Combining
      urinary neutrophil gelatinase-associated lipocalin with a novel creatinine-based
      metric, both available soon after completion of surgery, may provide previously
      unavailable early and effective risk stratification for serious adverse outcomes
      after cardiac surgery.

PMID- 25768683
TI  - Intraosseous versus central venous catheter utilization and performance during
      inpatient medical emergencies.
AB  - OBJECTIVES: Intraosseous access is a rapid and effective route of fluid and drug
      administration. Its use has been proven in emergency medicine, pediatrics, and
      the military. We aimed to assess its performance and utilization against landmark
      guided central venous catheter placement during inpatient medical emergencies.
      DESIGN: Prospective observational study. SETTING: Eight hundred fifty-six-bed
      urban teaching hospital. PATIENTS: Adult inpatients requiring central venous
      access during medical emergencies. INTERVENTIONS: Intraosseous device training
      was added to standard central venous catheter training beginning in February
      2012. Intraosseous were used as primary access in cardiac arrests and secondary
      access if central venous catheter placement failed during noncardiac arrest
      emergencies. An online survey was conducted among intraosseous and central venous
      catheter operators to assess their experience and any barriers to use.
      MEASUREMENTS AND MAIN RESULTS: Seventy-nine adults had central access placement
      from February 2012 to July 2013. Sixty were during medical emergency team calls,
      and 19 were cardiac arrests. Thirty-one received intraosseous device, and 48
      received a central venous catheter. First-pass success was significantly higher
      for intraosseous than for central venous catheter (90.3 vs 37.5%; 95% CI, 80-101
      vs 24-51; p<0.001). Mean placement times were significantly shorter for
      intraosseous than for central venous catheter (1.2 vs 10.7 min; p<0.001). There
      were a total of 33 intraosseous versus 169 central venous catheter attempts with
      fewer attempts on average per patient during intraosseous placement (1.1 vs 2.8;
      p<0.001). There were three intraosseous-related complications and 22 central
      venous catheter-related complications. Our survey showed high satisfaction with
      intraosseous training and operation. Among the barriers cited, timely
      intraosseous kit acquisition was most common. CONCLUSIONS: It is feasible to
      incorporate intraosseous use during medical emergency team calls. Intraosseous
      had significantly higher first-pass success rates and faster placement compared
      with central venous catheters. Intraosseous operators reported high satisfaction
      and confidence in its use. Prospective randomized studies comparing intraosseous
      and central venous catheter are warranted.

PMID- 25768682
TI  - Comparative Effectiveness of Noninvasive and Invasive Ventilation in Critically
      Ill Patients With Acute Exacerbation of Chronic Obstructive Pulmonary Disease.
AB  - OBJECTIVES: To compare the characteristics and hospital outcomes of patients with
      an acute exacerbation of chronic obstructive pulmonary disease treated in the ICU
      with initial noninvasive ventilation or invasive mechanical ventilation. DESIGN:
      Retrospective, multicenter cohort study of prospectively collected data. We used
      propensity matching to compare the outcomes of patients treated with noninvasive
      ventilation to those treated with invasive mechanical ventilation. We also
      assessed predictors for noninvasive ventilation failure. SETTING: Thirty-eight
      hospitals participating in the Acute Physiology and Chronic Health Evaluation
      database from 2008 through 2012. SUBJECTS: A total of 3,520 patients with a
      diagnosis of chronic obstructive pulmonary disease exacerbation including 27.7%
      who received noninvasive ventilation and 45.5% who received invasive mechanical
      ventilation. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Noninvasive
      ventilation failure was recorded in 13.7% from patients ventilated noninvasively.
      Hospital mortality was 7.4% for patients treated with noninvasive ventilation;
      16.1% for those treated with invasive mechanical ventilation; and 22.5% for those
      who failed noninvasive ventilation. In the propensity-matched analysis, patients
      initially treated with noninvasive ventilation had a 41% lower risk of death
      compared with those treated with invasive mechanical ventilation (relative risk,
      0.59; 95% CI, 0.36-0.97). Factors that were independently associated with
      noninvasive ventilation failure were Simplified Acute Physiology Score II
      (relative risk = 1.04 per point increase; 95% CI, 1.03-1.04) and the presence of
      cancer (2.29; 95% CI, 0.96-5.45). CONCLUSIONS: Among critically ill adults with
      chronic obstructive pulmonary disease exacerbation, the receipt of noninvasive
      ventilation was associated with a lower risk of in-hospital mortality compared
      with that of invasive mechanical ventilation; noninvasive ventilation failure was
      associated with the worst outcomes. These results support the use of noninvasive
      ventilation as a first-line therapy in appropriately selected critically ill
      patients with chronic obstructive pulmonary disease while also highlighting the
      risks associated with noninvasive ventilation failure and the need to be cautious
      in the face of severe disease.

PMID- 25768684
TI  - The Neck Disability Index-Russian Language Version (NDI-RU): A Study of Validity
      and Reliability.
AB  - STUDY DESIGN: Cross-cultural adaptation and psychometric testing. OBJECTIVE: To
      perform a validated Russian translation and then to evaluate the validity and
      reliability of the Russian language version of the Neck Disability Index (NDI
      RU). SUMMARY OF BACKGROUND DATA: Neck pain is highly prevalent and can greatly
      affect daily activity. The Neck Disability Index (NDI) is the most frequently
      used scale for self-rating of disability due to neck pain. Its translated
      versions are applied in many countries. However, the Russian language version of
      the NDI has not been developed yet. METHODS: Cross-cultural adaptation of the NDI
      RU was performed according to established guidelines. Then, the NDI-RU was
      evaluated for content validity, concurrent criterion validity, internal
      consistency, test-retest reliability, factor structure, and minimum detectable
      change. RESULTS: Two hundred thirty-two patients took part in the study in total:
      109 in validity (39.5 +/- 10 yr), 123 in reliability (38.4 +/- 11 yr; 80 in the
      test-retest phase). A culturally valid translation was achieved. NDI-RU total
      scores were distributed normally. Floor/ceiling effects were absent. Good values
      of Cronbach alpha were obtained for each item (from 0.80 to 0.84) and for the
      total NDI-RU (0.83). A 2-factor solution was found for the NDI-RU. The average
      interitem correlation coefficient was 0.53. Intraclass correlation coefficients
      for test-retest reliability coefficients ranged from 0.65 to 0.92 for different
      items and 0.91 for the total NDI-RU. Moderate correlation (Spearman rs = 0.62; P
      < 0.05) was found between the NDI-RU total score and graphic rating scalepain
      score. Completion of the NDI-RU takes 3.6 +/- 1 minutes. CONCLUSION: The
      development of a Russian language version of the Neck Disability Index resulted
      in a valid, reliable instrument that can be used both in clinical practice and
      scientific investigations. LEVEL OF EVIDENCE: 1.

PMID- 25768685
TI  - Postural Consequences of Cervical Sagittal Imbalance: A Novel Laboratory Model.
AB  - STUDY DESIGN: A biomechanical study using human spine specimens. OBJECTIVE: To
      study postural compensations in lordosis angles that are necessary to maintain
      horizontal gaze in the presence of forward head posture and increasing T1
      sagittal tilt. SUMMARY OF BACKGROUND DATA: Forward head posture relative to the
      shoulders, assessed radiographically using the horizontal offset distance between
      the C2 and C7 vertebral bodies (C2-C7 [sagittal vertical alignment] SVA), is a
      measure of global cervical imbalance. This may result from kyphotic alignment of
      cervical segments, muscle imbalance, as well as malalignment of thoracolumbar
      spine. METHODS: Ten cadaveric cervical spines (occiput-T1) were tested. The T1
      vertebra was anchored to a tilting and translating base. The occiput was free to
      move vertically but its angular orientation was constrained to ensure horizontal
      gaze regardless of sagittal imbalance. A 5-kg mass was attached to the occiput to
      mimic head weight. Forward head posture magnitude and T1 tilt were varied and
      motions of individual vertebrae were measured to calculate C2-C7 SVA and lordosis
      across C0-C2 and C2-C7. RESULTS: Increasing C2-C7 SVA caused flexion of lower
      cervical (C2-C7) segments and hyperextension of suboccipital (C0-C1-C2) segments
      to maintain horizontal gaze. Increasing kyphotic T1 tilt primarily increased
      lordosis across the C2-C7 segments. Regression models were developed to predict
      the compensatory C0-C2 and C2-C7 angulation needed to maintain horizontal gaze
      given values of C2-C7 SVA and T1 tilt. CONCLUSION: This study established
      predictive relationships between radiographical measures of forward head posture,
      T1 tilt, and postural compensations in the cervical lordosis angles needed to
      maintain horizontal gaze. The laboratory model predicted that normalization of C2
      C7 SVA will reduce suboccipital (C0-C2) hyperextension, whereas T1 tilt reduction
      will reduce the hyperextension in the C2-C7 segments. The predictive
      relationships may help in planning corrective strategy in patients experiencing
      neck pain, which may be attributed to sagittal malalignment. LEVEL OF EVIDENCE:
      N/A.

PMID- 25768686
TI  - Large Increase in Blood Pressure After Extubation and High Body Mass Index
      Elevate the Risk of Spinal Epidural Hematoma After Spinal Surgery.
AB  - STUDY DESIGN: Matched case-control study. OBJECTIVE: To identify factors other
      than a multilevel procedure that increase the risk of symptomatic postoperative
      spinal epidural hematoma (SEH). SUMMARY OF BACKGROUND DATA: Postoperative SEH is
      a potentially devastating complication of spinal surgery. Previous studies that
      reported risk factors for postoperative SEH all identified a multilevel procedure
      as a risk factor, but the other risk factors remain unclear. METHODS: Patients
      who developed postoperative SEH requiring surgical evacuation were identified
      from database. Each patient was matched with 3 controls who underwent spinal
      decompression at the same number of levels in the same part of the spine by the
      same surgeon during the preceding or following year. Multiple logistic regression
      analysis was performed to identify the risk factors for postoperative SEH to
      obtain adjusted odds ratios with 95% confidence intervals. Clinical outcomes
      after evacuation were investigated separately divided with or without severe
      paralysis or time until the second surgery. RESULTS: Postoperative SEH evacuation
      was performed after 32 of 8250 (0.39%) spinal decompression procedures. The
      incidence was significantly higher after thoracic procedures (2.41%) than after
      cervical (0.21%) or lumbar (0.39%) procedures. Multivariate analysis identified a
      50 mm Hg or greater increase in systolic blood pressure after extubation
      (adjusted odds ratio: 3.22, 95% confidence interval: 1.22-8.51) and higher body
      mass index (adjusted odds ratio 1.15, 95% confidence interval: 1.01-1.31) as risk
      factors. Among 14 patients with severe paralysis due to postoperative SEH, those
      who underwent evacuation within 24 hours of the onset had a significantly better
      improvement in clinical outcome and Frankel grade than did those after 24 hours.
      CONCLUSION: A 50 mm Hg or greater increase in systolic blood pressure after
      extubation and high body mass index were identified as risk factors for SEH.
      Appropriate blood pressure control especially at the end of surgery is important
      for the prevention of postoperative SEH, particularly in obese patients. LEVEL OF
      EVIDENCE: 3.

PMID- 25768687
TI  - Mechanical Contribution of the Rib Cage in the Human Cadaveric Thoracic Spine.
AB  - STUDY DESIGN: An in vitro biomechanical human cadaveric study of T1-T12 thoracic
      specimens was performed with 4 conditions (with and without rib cage,
      instrumented and uninstrumented) in flexion-extension, lateral bending, and axial
      rotation. OBJECTIVE: The objective was to understand the influence of the rib
      cage on motion and stiffness parameters of the human cadaveric thoracic spine.
      Hypotheses tested for overall motion in all modes of bending for both
      uninstrumented and instrumented specimens were (i) in-plane range of motion and
      neutral and elastic zones will be greater without the rib cage, (ii) neutral and
      elastic zone stiffness values will be different for specimens without the rib
      cage, and (iii) out-of-plane rotations will be different for specimens without
      the rib cage. SUMMARY OF BACKGROUND DATA: The rib cage is presumed to provide
      significant stability to the thoracic spine, but no studies have been conducted
      to determine the influence of the rib cage in both uninstrumented and
      instrumented conditions in the full thoracic human cadaveric specimens. METHODS:
      Seven human cadaveric spine specimens (T1-T12) with 4 conditions (with and
      without rib cage, instrumented and uninstrumented) were subjected to 5 N.m pure
      moments in flexion-extension, lateral bending, and axial rotation. Range of
      motion, neutral and elastic zones, neutral and elastic zone stiffness values, and
      out-of-plane rotations were calculated for the overall specimen. RESULTS: In
      plane range of motion was significantly higher without a rib cage for most modes
      of bending. Out-of-plane motions were also influenced by the rib cage. Neutral
      zone stiffness was significantly higher with a rib cage present. CONCLUSION:
      Testing without a rib cage yields different motion and stiffness measures,
      directly impacting the translation of research results to clinical
      interpretation. Researchers should consider these differences when evaluating the
      mechanical impact of surgical procedures or instrumentation in cadaveric or
      computational models. LEVEL OF EVIDENCE: 5.

PMID- 25768688
TI  - The Fate of L5-S1 With Low-Dose BMP-2 and Pelvic Fixation, With or Without
      Interbody Fusion, in Adult Deformity Surgery.
AB  - STUDY DESIGN: Retrospective comparative case series. OBJECTIVE: Evaluate L5-S1
      fusion rates when lower dose of bone morphogenic protein-2 (BMP-2) (average 3.2
      mg) and pelvic fixation were used, with or without interbody fusion. SUMMARY OF
      BACKGROUND DATA: Pseudarthrosis at L5-S1 is one of the most common complications
      of long fusions to the sacrum in adult deformity surgery. Strategies for
      decreasing pseudarthrosis include interbody fusion, use of BMP-2 at the
      lumbosacral junction, and the use of sacropelvic fixation, individually or in
      combination. High-dose BMP-2 (20-40 mg) placed posterolaterally has shown
      comparable fusion rates with interbody fusion. METHODS: Retrospective review of
      61 consecutive patients with minimum 2-year follow-up at a single institution.
      All patients had an isolated posterior approach, 5 or more levels fused including
      L5-S1, use of pelvic fixation, and no prior L5-S1 procedures. The patients were
      divided in 2 groups for comparison on the basis of the use of an interbody
      cage/fusion at the L5-S1 level. Revision rates and implant-related complications
      were also reported. RESULTS: The fusion rate at L5-S1 was 97% (59/61), with no
      difference between the interbody and no interbody fusion groups (97% vs. 96%, P =
      1.0). There were no significant differences in the radiographical parameters or
      deformity correction between the groups. The mean amount of BMP-2 used in the
      interbody group was 4.1 mg (2-10), 2.5 mg (0-8) in the disc space, and 1.6 mg (0
      4) in the interbody cage, whereas there was no difference in the amount of
      recombinant human bone morphogenic protein-2 placed posterolaterally between the
      2 groups (interbody fusion = 1.6 vs. non-interbody fusion = 2.0 mg, P = 0.08)
      along with autograft and allograft. The overall revision rate for L5-S1 nonunion
      was 1.6%. CONCLUSION: The use of low dose of BMP-2 at the L5-S1 level in
      combination with sacropelvic fixation achieved satisfactory fusion rates in adult
      deformity surgery. No additional benefit was encountered by adding an interbody
      cage. LEVEL OF EVIDENCE: 4.

PMID- 25768689
TI  - Reliability of Coronal Curvature Measures in Premature Scoliosis: Comparison of 4
      Methods Using Inverted Digital Luminescence Radiography.
AB  - STUDY DESIGN: Observational study with 4 examiners. OBJECTIVE: To improve the
      reproducibility and reliability of coronal curvature measurements. SUMMARY OF
      BACKGROUND DATA: Several different methods have been developed to measure coronal
      curvature. Inverted digital luminescence radiography may be an additional
      technique to improve the reliability of measurement methods. METHODS: A total of
      114 whole spine posterior-anterior radiographs were collected to compare the
      reliability of 4 measurement methods used in early onset scoliosis. Each
      radiograph was measured twice by each of 4 examiners using 4 measurement methods
      with normal and inversion views. Data were analyzed to determine inter- and
      intraobserver reliabilities. RESULTS: For all 4 methods, the overall
      intraobserver ICCs were greater than 0.926 and the interobserver ICCs were
      greater than 0.902, indicating excellent reliability. When intraobserver
      reliability was assessed in relation to scoliosis severity (<20 degrees , 20
      degrees -40 degrees , and >40 degrees ), the ICCs were higher for greater degrees
      of curvature; nonetheless, these values were in the excellent range for all
      methods and were higher for inversion (>0.908) than normal (>0.838) radiographs.
      For interobserver comparisons, the ICCs were better for the pedicle method
      (normal: >0.795, inversion: >0.831) than for the other methods (normal: >0.532,
      inversion: >0.590), with inverted digital luminescence radiography showing the
      higher ICCs. CONCLUSION: Inversion radiographs showed high reliability and may
      increase reliability in cases of less deformed spines. In addition, the pedicle
      method led to higher ICCs for all measurements regardless of severity, especially
      on inversion radiographs. LEVEL OF EVIDENCE: 2.

PMID- 25768690
TI  - Anterior Versus Posterior Approach for Multilevel Degenerative Cervical Disease:
      A Retrospective Propensity Score-Matched Study of the MarketScan Database.
AB  - STUDY DESIGN: Retrospective 2:1 propensity score-matched analysis on a national
      longitudinal database between 2006 and 2010. OBJECTIVE: To compare rates of
      adverse events, revisions procedure rates, and payment differences in anterior
      cervical fusion procedures compared with posterior laminectomy and fusion
      procedures with at least 3 levels of instrumentation. SUMMARY OF BACKGROUND DATA:
      The comparative benefits of anterior versus posterior approach to multilevel
      degenerative cervical disease remain controversial. Recent systematic reviews
      have reached conflicting conclusions. We demonstrate the comparative economic and
      clinical outcomes of anterior and posterior approaches for multilevel cervical
      degenerative disk disease. METHODS: We identified 13,662 patients in a national
      billing claims database who underwent anterior or posterior cervical fusion
      procedures with 3 or more levels of instrumentation. Cohorts were balanced using
      2:1 propensity score matching and outcomes were compared using bivariate
      analysis. RESULTS: With the exception of dysphagia (6.4% in anterior and 1.4% in
      posterior), overall 30-day complication rates were lower in the anterior approach
      group. The rate of any complication excluding dysphagia with anterior approaches
      was 12.3%, significantly lower (P < 0.0001) than that of posterior approaches,
      17.8%. Anterior approaches resulted in lower hospital ($18,346 vs. $23,638) and
      total payments ($28,963 vs. $33,526). Patients receiving an anterior surgical
      approach demonstrated significantly lower rate of 30-day readmission (5.1% vs.
      9.9%, P < 0.0001), were less likely to require revision surgery (12.8% vs. 18.1%,
      P < 0.0001), and had a shorter length of stay by 1.5 nights (P < 0.0001).
      CONCLUSION: Anterior approaches in the surgical management of multilevel
      degenerative cervical disease provide clinical advantages over posterior
      approaches, including lower overall complication rates, revision procedure rates,
      and decreased length of stay. Anterior approach procedures are also associated
      with decreased overall payments. These findings must be interpreted in light of
      limitations inherent to retrospective longitudinal studies including absence of
      subjective and radiographical outcomes. LEVEL OF EVIDENCE: 3.

PMID- 25768691
TI  - Reason for Lawsuit in Spinal Cord Injury Affects Final Outcome.
AB  - STUDY DESIGN: Retrospective cohort study. OBJECTIVE: To review past cases and
      analyze them to determine whether reason for lawsuit led to a defense versus
      plaintiff verdict when patients sustain spinal cord injury. Secondary objectives
      included analyzing demographic factors and monetary awards for plaintiff verdicts
      and settlements. SUMMARY OF BACKGROUND DATA: Evaluating malpractice cases could
      provide valuable information for the physician who has been sued by a patient.
      Previous studies about litigation and spine have been focused on medical tort
      reform and not on the reasons for litigation and lawsuit outcome. METHODS: A
      large national medicolegal research service for civil and criminal court called
      "VerdictSearch" was queried for "spinal cord injury" between the years 2000 and
      2010. Reason for lawsuit separated into 2 groups, error in diagnosis (n = 48),
      and error in treatment (n = 25). The anatomical region, outcome, cost, and job
      for sued health care workers recorded for each lawsuit. RESULTS: Compared with
      physicians who were sued for errors in diagnosis, those sued for an error of
      treatment had a relative risk of 2.69 (95% confidence interval, 1.40-5.16) to
      receive a defense verdict (P = 0.003). There were no significant differences in
      demographic information, including age, sex, occupation type, and level of
      injury. Among specialties, surgeons had the highest number of suits. The median
      value for each anatomic area was highest in thoracic spine ($1.90 million),
      followed by cervical spine ($1.80 million) and lumbar spine ($0.750 million),
      although there were no statistical differences between the 3 areas (P = 0.301).
      The median monetary award for a plaintiff verdict was higher than that for a
      settlement ($2.90 million, interquartile range: 1.50-12.5 million vs. $1.45
      million, interquartile range: 1.00-2.90 million, P = 0.008). CONCLUSION:
      Physicians are more likely to successfully defend a lawsuit for an error in
      treatment than for an error in diagnosis. The key to increase the success of
      defending a lawsuit in regard to spinal cord injury is to avoid delayed and
      incorrect diagnosis. LEVEL OF EVIDENCE: N/A.

PMID- 25768692
TI  - New chemical route for the synthesis of beta-Na(0.33)V2O5 and its fully
      reversible Li intercalation.
AB  - To obtain good electrochemical performance and thermal stability of rechargeable
      batteries, various cathode materials have been explored including NaVS2, beta
      Na(0.33)V2O5, and Li(x)V2O5. In particular, Li(x)V2O5 has attracted attention as
      a cathode material in Li-ion batteries owing to its large theoretical capacity,
      but its stable electrochemical cycling (i.e., reversibility) still remains as a
      challenge and strongly depends on its synthesis methods. In this study, we
      prepared the Li(x)V2O5 from electrochemical ion exchange of beta-Na(0.33)V2O5,
      which is obtained by chemical conversion of NaVS2 in air at high temperatures.
      Crystal structure and particle morphology of beta-Na(0.33)V2O5 are characterized
      by using X-ray diffraction, scanning electron microscopy, and transmission
      electron microscopy techniques. Energy-dispersive X-ray spectroscopy and X-ray
      photoelectron spectroscopy, in combination with electrochemical data, suggest
      that Na ions are extracted from beta-Na(0.33)V2O5 without irreversible structural
      collapse and replaced with Li ions during the following intercalation (i.e.,
      charging) process. The thus obtained Li(x)V2O5 delivers a high discharge capacity
      of 295 mAh g(-1), which corresponds to x = 2, with crystal structural stability
      in the voltage range of 1.5-4.0 V versus. Li, as evidenced by its good cycling
      performance and high Coulombic efficiency (under 0.1 mA cm(-2)) at room
      temperature. Furthermore, the ion-exchanged Li(x)V2O5 from beta-Na(0.33)V2O5
      shows stable electrochemical behavior without structural collapse, even at a case
      of deep discharge to 1.5 V versus Li.

PMID- 25768693
TI  - Understanding the pathological implications of MRI: application to focal therapy
      planning.
AB  - PURPOSE OF REVIEW: The current challenge in prostate cancer (PCa) focal therapy
      indication and planning is how to accurately estimate tumor parameters such as
      volume, extent and grade. In addition to biopsy results, MRI provides an
      estimation of PCa contour, volume and histopathological characteristics such as
      presence of high Gleason grade. Among MRI sequences, diffusion-weighted imaging
      with apparent diffusion coefficient map is the sequence that showed the best
      results for cancer aggressiveness characterization. RECENT FINDINGS: It was shown
      that the higher the Gleason score, the lower the apparent diffusion coefficient
      value. However, accuracy is not sufficient for peripheral zone cancers to be
      validated for clinical decision and it was not enough investigated for transition
      zone cancers. Analysis of tumor extent showed a significant underestimation of
      tumor volume by imaging and this finding should be taken into consideration when
      planning focal therapy procedures. SUMMARY: Pathological implications of MRI for
      focal therapy planning are significant but not mature enough to be validated.
      Future research should aim to quantify cellularity and architectural patterns of
      PCa Gleason system in correlation with signal abnormalities for better assessment
      of tumor aggressiveness and extent, and to compare the boundaries of tumors
      between MRI and histopathological evaluation in order to define an optimal
      treatment margin.

PMID- 25768694
TI  - Active surveillance for prostate cancer: can we modernize contemporary protocols
      to improve patient selection and outcomes in the focal therapy era?
AB  - PURPOSE OF REVIEW: In the absence of whole gland treatment for prostate cancer,
      both active surveillance and focal therapy share the common need of requiring a
      more thorough, detailed and precise analysis of the biological threats within the
      prostatic parenchyma if one chooses to monitor or selectively eradicate only
      specific neoplastic targets. In addition, focal therapy utilizes active
      surveillance post-treatment to monitor the untreated sectors of the prostate. We
      aim to evaluate the current modalities available to modernize active surveillance
      protocols in order to distinguish patients who may be safely observed from those
      who require intervention. RECENT FINDINGS: Traditional active surveillance
      protocols by today's standards are rudimentary given the rapidly evolving
      technologies now available to clinicians. There is growing evidence for the
      adoption and use of multiparametric MRI and MRI-targeted biopsy to identify and
      localize prostate cancers of higher stage and grade. In addition, serum markers
      and prostate tissue DNA, RNA and methylation markers provide novel information
      that extends beyond Gleason grade to better characterize and define prostate
      cancer prognosis. Current active surveillance protocols should incorporate these
      modalities to improve patient stratification to surveillance, focal or whole
      gland interventions. SUMMARY: Active surveillance protocols should be modernized
      to include cancer localization modalities and molecular prognostic markers to
      improve tumour characterization and better stratify men to surveillance, focal or
      radical intervention.

PMID- 25768695
TI  - "An unspoken world of unspoken things": a study identifying and exploring core
      beliefs underlying self-stigma among people living with HIV and AIDS in Ireland.
AB  - PRINCIPLES: Human immunodeficiency virus (HIV) related self-stigma--negative self
      judgements resulting in shame, worthlessness and self-blame - negatively
      influences access to care and treatment, and overall quality of life for people
      living with HIV (PLHIV). Despite evidence that high levels of self-stigma exist
      among PLHIV, and is experienced to a far greater extent than stigma received from
      the broader community, there is a paucity of research aimed at understanding
      causes and functions of self-stigma, and an absence of interventions to mitigate
      its harmful effects. Understanding the core beliefs underlying self-stigma is
      therefore essential. METHODS: This pilot study used a qualitative approach to
      analyse interviews and written statements to uncover core beliefs underlying self
      stigma, the functions thereof, and strategies used to overcome it, among a
      heterogeneous group of PLHIV in Ireland. RESULTS: Core beliefs underlying HIV
      related self-stigma were uncovered and grouped into four categories: disclosure;
      sexuality and sexual pleasure; self-perception; and body, illness and death.
      Reported functions of self-stigma included contributing to maintaining a "victim"
      status; providing protection against stigma received from others; and justifying
      non-disclosure of HIV status. To cope with self-stigma, participants highlighted:
      community involvement and professional development; personal development; and
      connection to others and sense of belonging. Findings were also used to create a
      conceptual framework. CONCLUSIONS: This study helps fill identified gaps in
      knowledge about self-stigma as experienced by PLHIV. By understanding the core
      beliefs driving self-stigma, it will be possible to create targeted interventions
      to challenge and overcome such beliefs, supporting PLHIV to achieve improved
      wellbeing and lead productive lives free of self-limitation and self-judgement.

PMID- 25768696
TI  - Urrets-Zavalia syndrome after Descemet membrane endothelial keratoplasty.
AB  - PURPOSE: To report a case of Urrets-Zavalia syndrome (UZS) after Descemet
      membrane endothelial keratoplasty (DMEK). METHODS: A 74-year-old woman with Fuchs
      endothelial dystrophy and inconspicuous ocular history developed UZS after DMEK
      surgery. The intraoperative and postoperative course is presented. RESULTS: After
      uneventful DMEK surgery, intraocular pressure was elevated up to 40 mm Hg on the
      first postoperative day. A small bleed from the peripheral wide-open iridectomy
      in the 12 o'clock position in the otherwise deep anterior chamber was observed.
      On the sixth postoperative day, a 4-mm-wide pupil, nonreactive to light, was
      noted. One year after surgery, the fixed medium mydriasis (4 mm) persisted and
      best-corrected vision was 0.1 logMAR. No pupillary reaction was noted after
      application of 0.2% or 2% pilocarpine. CONCLUSIONS: Filling the anterior chamber
      with air to secure fixation of a grafted Descemet membrane carries the risk of
      early acute postoperative ocular hypertension. This can lead to iris sphincter
      defects resulting in a fixed dilated pupil after DMEK surgery. Large patent
      iridectomy in the 12 o'clock position is insufficient to prevent this. Patients
      undergoing DMEK surgery should be informed about this potential complication.

PMID- 25768697
TI  - New heterocyclic hybrids of pyrazole and its bioisosteres: design, synthesis and
      biological evaluation as dual acting antimalarial-antileishmanial agents.
AB  - A new series of pyrazole derivatives were synthesized by hybridization with five
      membered heterocyclic moieties such as thiazoles, thiazolidinones, 1,3,4
      thiadiazoles and pyrazolines. The compounds were evaluated for their in vivo
      antimalarial activity against Plasmodium berghei infected mice and the most
      active derivatives were further examined for their in vitro antimalarial activity
      against chloroquine resistant (RKL9) strain of Plasmodium falciparum. Compounds
      2c, 2d, 4b, 4c, 4d, 5a, 6c, 8c and 9b had more than 90% parasite suppression
      activity of that found with the antimalarial reference standard drug, chloroquine
      phosphate and had lower IC50 values than chloroquine. Compounds 4b and 9b were
      the most active derivatives, and their activities were 5-fold higher than
      chloroquine. All the newly synthesized compounds were evaluated for their in
      vitro antileishmanial activity against Leishmania aethiopica promastigotes and
      amastigote. The results showed that compounds 2c, 2d, 3d, 4b, 4c, 4d and 5a had
      lower or similar IC50 values than the reference standard drugs, amphotericin B
      and miltefosine. Compound 3d had the highest antileishmanial activity.
      Collectively, compounds 2c, 2d, 4b, 4c, 4d and 5a exhibited dual activity against
      malaria and leishmaniasis and were safe and well tolerated by the experimental
      animals orally up to 300 mg/kg and parenterally up to 100 mg/kg.

PMID- 25768698
TI  - Luciferin and derivatives as a DYRK selective scaffold for the design of protein
      kinase inhibitors.
AB  - D-Luciferin is widely used as a substrate in luciferase catalysed bioluminescence
      assays for in vitro studies. However, little is known about cross reactivity and
      potential interference of D-luciferin with other enzymes. We serendipitously
      found that firefly luciferin inhibited the CDK2/Cyclin A protein kinase.
      Inhibition profiling of D-luciferin over a 103-protein kinase panel showed
      significant inhibition of a small set of protein kinases, in particular the DYRK
      family, but also other members of the CMGC-group, including ERK8 and CK2.
      Inhibition profiling on a 16-member focused library derived from D-luciferin
      confirms that D-luciferin represents a DYRK-selective chemotype of fragment-like
      molecular weight. Thus, observation of its inhibitory activity and the initial
      SAR information reported here promise to be useful for further design of protein
      kinase inhibitors with related scaffolds.

PMID- 25768699
TI  - Water-soluble isoindolo[2,1-a]quinoxalin-6-imines: in vitro antiproliferative
      activity and molecular mechanism(s) of action.
AB  - Water-soluble isoindoloquinoxalin (IIQ) imines and the corresponding acetates
      were conveniently prepared from the key intermediates 2-(2'-aminophenyl)-2H
      isoindole-1-carbonitriles obtained by a Strecker reaction between substituted 1,2
      dicarbaldehydes and 1,2-phenylenediamines. Both series were screened by the
      National Cancer Institute (Bethesda, MD) and showed potent antiproliferative
      activity against a panel of 60 human tumor cell lines. Several of the novel
      compounds showed GI50 values at a nanomolar level on the majority of the tested
      cell lines. Among IIQ derivatives, methoxy substituents at positions 3 and 8
      or/and 9 were especially effective in impairing cell cycle progression and
      inducing apoptosis in cancer cells. These effects were associated to IIQ-mediated
      impairment of tubulin polymerization at pharmacologically significant
      concentrations of tested compounds. In addition, impaired DNA topoisomerase I
      functions and perturbation in telomere architecture were observed in cells
      exposed to micromolar concentrations of IIQ derivatives. The above results
      suggest that IIQ derivatives exhibit multi-target cytotoxic activities. 

PMID- 25768701
TI  - Truncated structures used in search for new lead compounds and in a retrospective
      analysis of thienopyrimidine-based EGFR inhibitors.
AB  - An approach for optimization of epidermal growth factor receptor tyrosine kinase
      (EGFR-TK) inhibitors using truncated thienopyrimidine structures combined with
      enzymatic assay has been evaluated. This was done by synthesis and EGFR activity
      measurement of a series of fragment structures and their corresponding drug-model
      analogues. On average, the activity of the drug-like structures increased a ten
      fold as compared to the fragments. However, the potency of the drug-model
      compound could not be precisely predicted, visualising the typical challenge with
      linking substructures. Additionally, the activity data provided useful SAR
      information with respect to stereochemical preference and the structure
      requirements of the 4-amino group. A retrospective evaluation of binding
      efficiency in previously discovered thieno[2,3-d]pyrimidines, suggests a high
      probability of obtaining potent EGFR inhibitors if based on the 3-chloro-4
      fluoroaniline moiety. Compounds derived from (S)-2-hydroxy-1-phenylethylamine
      also have resulted in highly active EGFR-TK inhibitors. In contrast the 3
      ethynylaniline containing structures appears more difficult to develop.
      Thieno[2,3-d]pyrimidin-4-amines have also been used for construction of
      irreversible EGFR-TK inhibitors. The data indicate these compounds to possess sub
      optimal non-covalent interactions. 

PMID- 25768702
TI  - Blood-brain barrier permeable anticholinesterase aurones: synthesis, structure
      activity relationship, and drug-like properties.
AB  - A series of novel aurones bearing amine and carbamate functionalities at various
      positions (rings A and/or B) of the scaffold was synthesized and evaluated for
      their acetylcholinesterase and butyrylcholinesterase inhibitory activities.
      Structure-activity relationship study disclosed several potent submicromolar
      acetylcholinesterase inhibitors (AChEIs) particularly aurones bearing piperidine
      and pyrrolidine moieties at ring A or ring B. Bulky groups particularly
      methoxyls, and carbamate to a lesser extent, at either rings were also
      prominently featured in these AChEI aurones as exemplified by the
      trimethoxyaurone 4-3. The active aurones exhibited a lower butyrylcholinesterase
      inhibition. A 3'-chloroaurone 6-3 originally designed to improve the metabolic
      stability of the scaffold was the most potent of the series. Molecular docking
      simulations showed these AChEI aurones to adopt favourable binding modes within
      the active site gorge of the Torpedo californica AChE (TcAChE) including an
      unusual chlorine-pi interaction by the chlorine of 6-3 to establish additional
      bondings to hydrophobic residues of TcAChE. Evaluation of the potent aurones for
      their blood-brain barrier (BBB) permeability and metabolic stability using PAMPA
      BBB assay and in vitro rat liver microsomes (RLM) identified 4-3 as an aurone
      with an optimal combination of high passive BBB permeability and moderate CYP450
      metabolic stability. LC-MS identification of a mono-hydroxylated metabolite found
      in the RLM incubation of 4-3 provided an impetus for further improvement of the
      compound. Thus, 4-3, discovered within this present series is a promising, drug
      like lead for the development of the aurones as potential multipotent agents for
      Alzheimer's disease. 

PMID- 25768700
TI  - Pure enantiomers of benzoylamino-tranylcypromine: LSD1 inhibition, gene
      modulation in human leukemia cells and effects on clonogenic potential of murine
      promyelocytic blasts.
AB  - The pure enantiomers of the N-(2-, 3-, and 4-(2
      aminocyclopropyl)phenyl)benzamides hydrochlorides 11a-j were prepared and tested
      against LSD1 and MAO enzymes. The evaluation of the regioisomers 11a-j
      highlighted a net increase of the anti-LSD1 potency by shifting the benzamide
      moiety from ortho to meta and mainly to para position of tranylcypromine phenyl
      ring, independently from their trans or cis stereochemistry. In particular, the
      para-substituted 11a,b (trans) and 11g,h (cis) compounds displayed LSD1 and MAO-A
      inhibition at low nanomolar levels, while were less potent against MAO-B. The
      meta analogs 11c,d (trans) and 11i,j (cis) were in general less potent, but more
      efficient against MAO-A than against LSD1. In cellular assays, all the para and
      meta enantiomers were able to inhibit LSD1 by inducing Gfi-1b and ITGAM gene
      expression, with 11b,c and 11g-i giving the highest effects. Moreover, 11b and
      11g,h strongly inhibited the clonogenic potential of murine promyelocytic blasts.

PMID- 25768703
TI  - Synthesis and biological evaluation of 4-oxycoumarin derivatives as a new class
      of antifilarial agents.
AB  - A series of 4-oxycoumarin derivatives was synthesized, characterized and
      evaluated in vitro and in vivo for antifilarial activity against the human
      lymphatic filarial parasite, Brugia malayi. A majority of the compounds studied
      showed potent in vitro activity with low IC50 values in the micro molar (MUM)
      range (0.014-1.73 and 0.0056-0.43) against adult worms and microfilariae,
      respectively. Compounds 8 and 9 were identified to be the most promising
      antifilarial candidate molecules exhibiting activity in the nanomolar (nM) range.
      The IC50 values for compound 8 were 14 nM and 5.6 nM while for compound 9 were 94
      nM and 13 nM, respectively, for adult worm and microfilaria. These two compounds
      also displayed promising adulticidal activity (74.9 +/- 4.8% and 69.4 +/- 2.8%,
      respectively) in the primary rodent (jird) screen. This study also serves as a
      starting point for investigating structure-activity relationship with different
      amino substituents.

PMID- 25768704
TI  - Discovery of HCV NS5B thumb site I inhibitors: core-refining from benzimidazole
      to indole scaffold.
AB  - Hepatitis C virus (HCV) NS5B RNA-depended-RNA-polymerase (RdRp) is an essential
      enzyme in HCV viral replication and has no functional equivalent in mammalian
      cells. Several classes of nucleoside and non-nucleoside inhibitors, targeting the
      different allosteric sites, have demonstrated efficacy in clinical trials.
      Compared to other allosteric sites, thumb site I is a more compelling allosteric
      target with a significant number of inhibitors in clinical trials. Among them,
      indole analogues are the most important series of NS5B thumb site I inhibitors
      with considerable antiviral activity. This review focuses on the discovery and
      development of indole inhibitors targeting on NS5B thumb site I. Five fundamental
      principles, the general structure-activity relationships (SARs) model of indole
      scaffold, were summarized, which could pave the way for further structural
      optimization of indole-based anti-HCV agents. 

PMID- 25768705
TI  - Synthesis, biological evaluation and molecular modeling studies of the
      PPARbeta/delta antagonist CC618.
AB  - Herein, we describe the synthesis, biological evaluation and molecular docking of
      the selective PPARbeta/delta antagonist (4-methyl-2-(4-(trifluoromethyl)phenyl)-N
      (2-(5-(trifluoromethyl)-pyridin-2-ylsulfonyl)ethyl)thiazole-5-carboxamide)),
      CC618. Results from in vitro luciferase reporter gene assays against the three
      known human PPAR subtypes revealed that CC618 selectively antagonizes agonist
      induced PPARbeta/delta activity with an IC50 = 10.0 MUM. As observed by LC-MS/MS
      analysis of tryptic digests, the treatment of PPARbeta/delta with CC618 leads to
      a covalent modification of Cys249, located centrally in the PPARbeta/delta ligand
      binding pocket, corresponding to the conversion of its thiol moiety to a 5
      trifluoromethyl-2-pyridylthioether. Finally, molecular docking is employed to
      shed light on the mode of action of the antagonist and its structural
      consequences for the PPARbeta/delta ligand binding pocket.

PMID- 25768706
TI  - A facile synthesis and microtubule-destabilizing properties of 4-(1H
      benzo[d]imidazol-2-yl)-furazan-3-amines.
AB  - A series of 4-(1H-benzo[d]imidazol-2-yl)-furazan-3-amines (BIFAs) were prepared
      in good yields (60-90% for each reaction step) via a novel procedure from
      aminofurazanyl hydroximoyl chlorides and o-diaminobenzenes. The synthetic
      sequence was run under mild reaction conditions, it was robust and did not
      require extensive purification of intermediates or final products. Furthermore,
      there was no need for protection of reactive moieties allowing for the parallel
      synthesis of diverse BIFA derivatives. Subsequent biological evaluation of the
      resulting compounds revealed their anti-proliferative effects in the sea urchin
      embryo model and in cultured human cancer cell lines. The most active compounds
      showed 0.2-2 MUM activities in both assay systems. The unsubstituted benzene ring
      of the benzoimidazole template as well as the unsubstituted amino group in the
      furazan ring were essential prerequisites for the antimitotic activity of BIFAs.
      Compound 57 bearing the 2-chlorophenyl acetamide substituent at the nitrogen atom
      of the imidazole ring was the most active molecule in the examined set.

PMID- 25768707
TI  - General role of the amino and methylsulfamoyl groups in selective
      cyclooxygenase(COX)-1 inhibition by 1,4-diaryl-1,2,3-triazoles and validation of
      a predictive pharmacometric PLS model.
AB  - A novel set of 1,4-diaryl-1,2,3-triazoles were projected as a tool to study the
      effect of both the heteroaromatic triazole as a core ring and a variety of
      chemical groups with different electronic features, size and shape on the
      catalytic activity of the two COX isoenzymes. The new triazoles were synthesized
      in fair to good yields and then evaluated for their inhibitory activity towards
      COXs arachidonic acid conversion catalysis. Their COXs selectivity was also
      measured. A predictive pharmacometric Volsurf plus model, experimentally
      confirmed by the percentage (%) of COXs inhibition at the concentration of 50 MUM
      and IC50 values of the tested compounds, was built by using a number of
      isoxazoles of known COXs inhibitory activity as a training set. It was found that
      two compounds {4-(5-methyl-4-phenyl-1H-1,2,3-triazol-1-yl)benzenamine (18) and 4
      [1-(4-methoxyphenyl)-5-methyl-1H-1,2,3-triazole-4-yl]benzenamine (19)} bearing an
      amino group (NH2) are potent and selective COX-1 inhibitors (IC50 = 15 and 3 MUM,
      respectively) and that the presence of a methylsulfamoyl group (SO2CH3) is not a
      rule to have a Coxib. In fact, 4-(4-methoxyphenyl)-5-methyl-1-[4
      (methylsulfonyl)phenyl]-1H-1,2,3-triazole (23) has COX-1 IC50 = 23 MUM and was
      found inactive towards COX-2.

PMID- 25768708
TI  - Motion corrected LV quantification based on 3D modelling for improved functional
      assessment in cardiac MRI.
AB  - Cine MRI is a clinical reference standard for the quantitative assessment of
      cardiac function, but reproducibility is confounded by motion artefacts. We
      explore the feasibility of a motion corrected 3D left ventricle (LV)
      quantification method, incorporating multislice image registration into the 3D
      model reconstruction, to improve reproducibility of 3D LV functional
      quantification. Multi-breath-hold short-axis and radial long-axis images were
      acquired from 10 patients and 10 healthy subjects. The proposed framework reduced
      misalignment between slices to subpixel accuracy (2.88 to 1.21 mm), and improved
      interstudy reproducibility for 5 important clinical functional measures, i.e. end
      diastolic volume, end-systolic volume, ejection fraction, myocardial mass and 3D
      sphericity index, as reflected in a reduction in the sample size required to
      detect statistically significant cardiac changes: a reduction of 21-66%. Our
      investigation on the optimum registration parameters, including both cardiac time
      frames and number of long-axis (LA) slices, suggested that a single time frame is
      adequate for motion correction whereas integrating more LA slices can improve
      registration and model reconstruction accuracy for improved functional
      quantification especially on datasets with severe motion artefacts. 

PMID- 25768709
TI  - Additional effect of occlusal splints on the improvement of psychological aspects
      in temporomandibular disorder subjects: A randomized controlled trial.
AB  - OBJECTIVE: To measure the effect of occlusal splints as an additional treatment
      on psychological aspects in temporomandibular disorder patients. DESIGN: A
      randomized controlled trial was performed comprising 60 adults diagnosed with
      masticatory myofascial pain according the Research Diagnostic Criteria for
      Temporomandibular Disorders (RDC/TMD). The participants were divided equally into
      2 treatment groups, which received only counselling (Group 1) or occlusal splints
      in addition to counselling (Group 2). The assessments occurred at baseline and at
      2 and 5 months after treatment. The outcomes were symptoms of anxiety and
      depression, as well as pain catastrophizing. Two-way ANOVA, Friedman and Mann
      Whitney tests were used to perform the statistical analysis, considering a
      significance level of 5%. RESULTS: In relation to the baseline assessment, 60% of
      the subjects had at least mild anxiety and 25% had at least mild depression, and
      the mean and standard deviation (SD) of pain catastrophizing was 2.41 (1.33) for
      Group 1 and 2.06 (1.04) for Group 2. Comparisons between baseline and the fifth
      month evaluation showed an improvement in anxiety and depression symptoms only in
      Group 2 (p<0.05). Otherwise, there was a significant reduction in pain
      catastrophizing in both groups (p<0.05), with a mean (SD) of 1.14 (1.28) for
      Group 1 and 0.76 (0.82) for Group 2. CONCLUSION: Minimally invasive strategies
      could provide an improvement in the psychological aspects of temporomandibular
      disorder patients, and the use of an occlusal splint seems to hasten the
      manifestation of these effects.

PMID- 25768710
TI  - Vascular risk factors, vascular disease, lipids and lipid targets in patients
      with familial dysbetalipoproteinemia: a European cross-sectional study.
AB  - BACKGROUND: Familial dysbetalipoproteinemia (FD), also known as type III
      hyperlipoproteinemia, is a genetic dyslipidemia characterized by elevated very
      low density lipoprotein (VLDL) and chylomicron remnant particles that confers
      increased risk of cardiovascular disease (CVD). The objective of this study was
      to evaluate the prevalence of vascular risk factors, CVD, lipid values, treatment
      and lipid targets in patients with FD across Europe. METHODS: This cross
      sectional study was performed in 305 patients with FD from seven academic
      hospitals in four European countries. Information was collected from clinical
      records. RESULTS: Patients mean (+/-standard deviation) age was 60.9+/-14.4
      years, 201 (66%) were male, 69 (23%) had diabetes mellitus (DM) and 87 (29%) had
      a prior history of CVD. Mean body mass index was 28.5+/-5.0 kg/m2. Lipid-lowering
      medication was used by 227 (74%) patients (27% usual dose (theoretical low
      density lipoprotein cholesterol (LDL-C) reduction<=40%) and 46% intensive dose
      (theoretical LDL-C reduction>40%)). Non high-density lipoprotein cholesterol (non
      HDL-C) levels below treatment target (<3.3 mmol/L) were present in 123 (40%)
      patients and 163 patients (53%) had LDL-C levels below target (<2.5 mmol/L). No
      significant determinants were found for having non-HDL-C levels below target,
      while a prior history of CVD (OR 1.90, 95%CI 1.05-3.47) and presence of DM (OR
      2.00, 95%CI 1.08-3.70) were associated with having LDL-C levels below treatment
      target. CONCLUSION: The majority of FD patients had non-HDL-C levels above the
      treatment target of 3.3 mmol/L. Intensive dose lipid-lowering medication was used
      by only half of the patients, leaving them at increased cardiovascular risk.

PMID- 25768711
TI  - Memory outcome following left anterior temporal lobectomy in patients with a
      failed Wada test.
AB  - PURPOSE: This study aimed to compare the memory outcome following left anterior
      temporal lobectomy (ATL) between patients with a failed Wada test and patients
      who passed the Wada test. METHODS: From 1996 to 2002, we performed the Wada test
      on all patients with unilateral left mesial temporal lobe epilepsy with
      hippocampal sclerosis (MTLE-HS) and concordant electroclinical data before ATL.
      We used a 12-item recognition paradigm for memory testing and awarded a score of
      +1 for each correct response and -0.5 for each incorrect response. No patient was
      denied surgery on the basis of Wada scores. We assessed cognitive and memory
      functions using the Wechsler Adult Intelligence Scale and the Wechsler Memory
      Scale preoperatively and at one year after ATL. We compared the number of
      patients who showed decline in memory scores, as per the published reliable
      change indices, between the patients with a failed Wada test and the patients who
      passed the Wada test. RESULTS: Out of the 116 eligible patients with left MTLE
      HS, 88 underwent bilateral Wada test, while 28 underwent ipsilateral Wada test.
      None of them developed postoperative amnesia. Approximately, one-third of
      patients with a failed Wada memory test when the failure was defined as a
      contralateral score of <4, as an ipsilateral score of >8, and as an asymmetry
      score of <0. The patients with Wada memory failure had a longer pre-ATL duration
      of epilepsy (p<0.003). The memory and quality-of-life outcomes did not differ
      between the group with a failed Wada memory test and the group who passed the
      Wada memory test. The results remained the same when analyses were repeated at
      various other cutoff points. CONCLUSION: The patients with left MTLE-HS with
      concordant electroclinical, MRI, and neuropsychological data should not be denied
      ATL solely on the basis of Wada memory test results.

PMID- 25768712
TI  - Impact of health education on drug adherence and self-care in people with
      epilepsy with low education.
AB  - PURPOSE: This study was conducted to observe the effect of a structured
      educational program on drug adherence and self-care management in people with
      epilepsy in a developing country. METHODS: A total of 180 consecutive people with
      epilepsy were enrolled from the epilepsy clinic of a tertiary care hospital in
      North India. Out of these, 90 were randomized to the epilepsy health education
      group and received the educational program and 90 were in the control group and
      received the standard of care but did not receive any structured educational
      program. The modified Morisky Medication Adherence Scale (MMAS) and Epilepsy Self
      Efficacy Scale (ESES) were administered to assess drug adherence and self-care,
      respectively, on the day of enrollment. The patients enrolled in the epilepsy
      health education group received 4 sessions of the structured educational program.
      The MMAS and ESES questionnaires were again administered to both groups after
      6months. STATISTICAL METHODS: Continuous and categorical variables were compared
      between control and epilepsy health education groups using a chi-square test,
      with p value less than 0.05 considered significant. A comparison between pretest
      and posttest MMAS scores and ESES scores was done using a paired t-test. RESULTS:
      In the epilepsy health education group, the pretest mean MMAS score was 6.58
      whereas the posttest mean MMAS score was 7.53; the difference was significant
      (p=0.001). The mean MMAS scores for the control group's pretest and posttest were
      6.46 and 6.58, respectively, which were not significantly different (p=0.224). On
      comparing the ESES scores at the beginning of the study and after 6months, there
      was no significant change in both groups. CONCLUSIONS: The present study proves
      the efficacy of a structured educational program in improving drug adherence in a
      cohort of people with epilepsy with low educational background.

PMID- 25768713
TI  - Integrating groundwater into land planning: a risk assessment methodology.
AB  - Generally, groundwater is naturally of good quality for human consumption and
      represents an essential source of drinking water. In Canada, small municipalities
      and individuals are particularly reliant on groundwater, since they cannot afford
      complex water treatment installations. However, groundwater is a vulnerable
      resource that, depending on its characteristics, can be contaminated by almost
      any land use. In recent decades, governments have launched programs to acquire
      more information on groundwater, in order to better protect it. Nevertheless, the
      data produced are rarely adequate to be understood and used by land planners. The
      aim of this study was to develop a method that helps planners interpret
      hydrogeological data in the Province of Quebec, Canada. Based on the requests and
      needs of planners during semi-directed interviews, a methodology was developed to
      qualitatively evaluate groundwater contamination risk by land uses. The method
      combines land planning data and hydrogeological data through the MACBETH
      multicriteria analysis method, to obtain maps of groundwater contamination risk.
      The method was developed through group and individual meetings with numerous
      hydrogeology, land planning, water's economics and drinking water specialists.
      The resulting maps allow planners to understand the dynamics of groundwater
      within their territory, identify problem areas where groundwater is threatened
      and analyse the potential impact of planning scenarios on the risk of groundwater
      contamination. 

PMID- 25768714
TI  - Multiple stressor effects in Chlamydomonas reinhardtii--toward understanding
      mechanisms of interaction between effects of ultraviolet radiation and chemical
      pollutants.
AB  - The effects of chemical pollutants and environmental stressors, such as
      ultraviolet radiation (UVR), can interact when organisms are simultaneously
      exposed, resulting in higher (synergistic) or lower (antagonistic) multiple
      stressor effects than expected based on the effects of single stressors. Current
      understanding of interactive effects is limited due to a lack of mechanism-based
      multiple stressor studies. It has been hypothesized that effect interactions may
      generally occur if chemical and non-chemical stressors cause similar
      physiological effects in the organism. To test this hypothesis, we exposed the
      model green alga Chlamydomonas reinhardtii to combinations of UVR and single
      chemicals displaying modes of action (MOA) similar or dissimilar to the impact of
      UVR on photosynthesis. Stressor interactions were analyzed based on the
      independent action model. Effect interactions were found to depend on the MOA of
      the chemicals, and also on their concentrations, the exposure time and the
      measured endpoint. Indeed, only chemicals assumed to cause effects on
      photosynthesis similar to UVR showed interactions with UVR on photosynthetic
      yield: synergistic in case of Cd(II) and paraquat and antagonistic in case of
      diuron. No interaction on photosynthesis was observed for S-metolachlor, which
      acts dissimilarly to UVR. However, combined effects of S-metolachlor and UVR on
      algal reproduction were synergistic, highlighting the importance of considering
      additional MOA of UVR. Possible mechanisms of stressor effect interactions are
      discussed. 

PMID- 25768715
TI  - New frontiers and treatment paradigms for thyroid carcinoma.

PMID- 25768720
TI  - The probabilistic aggregate consumer exposure model (PACEM): validation and
      comparison to a lower-tier assessment for the cyclic siloxane D5.
AB  - Current practice of chemical risk assessment for consumer product ingredients
      still rarely exercises the aggregation of multi-source exposure. However,
      focusing on a single dominant source/pathway combination may lead to a
      significant underestimation of the risk for substances present in numerous
      consumer products, which often are used simultaneously. Moreover, in most cases
      complex multi-route exposure scenarios also need to be accounted for. This paper
      introduces and evaluates the performance of the Probabilistic Aggregate Consumer
      Exposure Model (PACEM) applied in the context of a tiered approach to exposure
      assessment for ingredients in cosmetics and personal care products (C&PCPs) using
      decamethylcyclopentasiloxane (D5) as a worked example. It is demonstrated that
      PACEM predicts a more realistic, but still conservative aggregate exposure within
      the Dutch adult population when compared to a deterministic point estimate
      obtained in a lower tier screening assessment. An overall validation of PACEM is
      performed by quantitatively relating and comparing its estimates to currently
      available human biomonitoring and environmental sampling data. Moderate (by
      maximum one order of magnitude) overestimation of exposure is observed due to a
      justified conservatism built into the model structure, resulting in the tool
      being suitable for risk assessment. 

PMID- 25768721
TI  - Oxidation of cholesterol does not alter significantly its uptake into high
      density lipoprotein particles.
AB  - Using replica exchange umbrella sampling we calculated free energy profiles for
      uptake of cholesterol and one of its oxysterols (7-ketocholesterol) from an
      aqueous solution into a high-density lipoprotein particle. These atomistic
      molecular dynamics simulations show that both sterols are readily taken up from
      the aqueous solution with comparable free energy minima at the surface of the
      particle of -17 kcal/mol for cholesterol and -14 kcal/mol for 7-ketocholesterol.
      Moreover, given its preferred position at the particle surface, 7-ketocholesterol
      is expected to be able to participate directly in biological signaling processes.

PMID- 25768722
TI  - In situ study of defect migration kinetics and self-healing of twin boundaries in
      heavy ion irradiated nanotwinned metals.
AB  - High energy particles introduce severe radiation damage in metallic materials,
      such as Ag. Here we report on the study on twin boundary (TB) affected zone in
      irradiated nanotwinned Ag wherein time accumulative defect density and defect
      diffusivity are substantially different from those in twin interior. In situ
      studies also reveal surprising resilience and self-healing of TBs in response to
      radiation. This study provides further support for the design of radiation
      tolerant nanotwinned metallic materials. 

PMID- 25768723
TI  - Defining regions of interest using cross-frequency coupling in extratemporal lobe
      epilepsy patients.
AB  - OBJECTIVE: Clinicians identify seizure onset zones (SOZs) for resection in an
      attempt to localize the epileptogenic zone (EZ), which is the cortical tissue
      that is indispensible for seizure generation. An automated system is proposed to
      objectively localize this EZ by identifying regions of interest (ROIs). METHODS:
      Intracranial electroencephalogram recordings were obtained from seven patients
      presenting with extratemporal lobe epilepsy and the interaction between neuronal
      rhythms in the form of phase-amplitude coupling was investigated. Modulation of
      the amplitude of high frequency oscillations (HFOs) by the phase of low frequency
      oscillations was measured by computing the modulation index (MI). Delta- (0.5-4
      Hz) and theta- (4-8 Hz) modulation of HFOs (30-450 Hz) were examined across the
      channels of a 64-electrode subdural grid. Surrogate analysis was performed and
      false discovery rates were computed to determine the significance of the
      modulation observed. Mean MI values were subjected to eigenvalue decomposition
      (EVD) and channels defining the ROIs were selected based on the components of the
      eigenvector corresponding to the largest eigenvalue. ROIs were compared to the
      SOZs identified by two independent neurologists. Global coherence values were
      also computed. MAIN RESULTS: MI was found to capture the seizure in time for six
      of seven patients and identified ROIs in all seven. Patients were found to have a
      poorer post-surgical outcome when the number of EVD-selected channels that were
      not resected increased. Moreover, in patients who experienced a seizure-free
      outcome (i.e., Engel Class I) all EVD-selected channels were found to be within
      the resected tissue or immediately adjacent to it. In these Engel Class I
      patients, delta-modulated HFOs were found to identify more of the channels in the
      resected tissue compared to theta-modulated HFOs. However, for the Engel Class IV
      patient, the delta-modulated HFOs did not identify any of the channels in the
      resected tissue suggesting that the resected tissue was not appropriate, which
      was also suggested by the Engel Class IV outcome. A sensitivity of 75.4% and a
      false positive rate of 15.6% were achieved using delta-modulated HFOs in an Engel
      Class I patient. SIGNIFICANCE: LFO-modulated HFOs can be used to identify ROIs in
      extratemporal lobe patients. Moreover, delta-modulated HFOs may provide more
      accurate localization of the EZ. These ROIs may result in better surgical
      outcomes when used to compliment the SOZs identified by clinicians for resection.

PMID- 25768724
TI  - Adsorption of lactate dehydrogenase enzyme on carbon nanotubes: how to get
      accurate results for the cytotoxicity of these nanomaterials.
AB  - Carbon nanotube (CNT) cytotoxicity is frequently investigated using in vitro
      classical toxicology assays. However, these cellular tests, usually based on the
      use of colorimetric or fluorimetric dyes, were designed for chemicals and may not
      be suitable for nanosized materials. Indeed, because of their unique
      physicochemical properties CNT can interfere with the assays and bias the
      results. To get accurate data and draw reliable conclusions, these artifacts
      should be carefully taken into account. The aim of this study was to evaluate
      qualitatively and quantitatively the interferences occurring between CNT and the
      commonly used lactate dehydrogenase (LDH) assay. Experiments under cell-free
      conditions were performed, and it was clearly demonstrated that artifacts
      occurred. They were due to the intrinsic absorbance of CNT on one hand and the
      adsorption of LDH at the CNT surface on the other hand. The adsorption of LDH on
      CNT was modeled and was found to fit the Langmuir model. The K(ads) and n(eq)
      constants were defined, allowing the correction of results obtained from cellular
      experiments to get more accurate data and lead to proper conclusions on the
      cytotoxicity of CNT.

PMID- 25768725
TI  - Mebamamides A and B, Cyclic Lipopeptides Isolated from the Green Alga Derbesia
      marina.
AB  - Mebamamides A and B, new lipopeptides with four d-amino acid residues and a 3,8
      dihydroxy-9-methyldecanoic acid residue, were isolated from the green alga
      Derbesia marina. Their gross structures were elucidated by spectroscopic and ESI
      ITMS analyses. The absolute configurations except for the two leucines were
      revealed based on chiral-phase HPLC analyses of the acid hydrolysate and a
      modified Mosher's method. A distinction between D-Leu and L-Leu in the sequence
      was established by the application of a dansyl-Edman method to the partial acid
      hydrolysate. Mebamamide A did not exhibit any growth inhibitory activity against
      HeLa and HL60 cells at 10 MUM, and mebamamide B did not exhibit any growth
      inhibitory activity against those cells at 100 MUM. Additionally, it was
      suggested that mebamamide B induced the differentiation of HL60 cells into
      macrophage-like cells at 100 MUM.

PMID- 25768726
TI  - Favorable alleles for stem water-soluble carbohydrates identified by association
      analysis contribute to grain weight under drought stress conditions in wheat.
AB  - Drought is a major environmental constraint to crop distribution and
      productivity. Stem water-soluble carbohydrates (WSC) buffer wheat grain yield
      against conditions unfavorable for photosynthesis during the grain filling stage.
      In this study, 262 winter wheat accessions and 209 genome-wide SSR markers were
      collected and used to undertake association analysis based on a mixed linear
      model (MLM). The WSC in different internodes at three growth stages and 1000
      grain weight (TGW) were investigated under four environmental regimes (well
      watered, drought stress during the whole growth period, and two levels of
      terminal drought stress imposed by chemical desiccation under the well-watered
      and drought stress during the whole growth period conditions). Under diverse
      drought stress conditions, WSC in lower internodes showed significant positive
      correlations with TGW, especially at the flowering stage under well-watered
      conditions and at grain filling under drought stress. Sixteen novel WSC-favorable
      alleles were identified, and five of them contributed to significantly higher
      TGW. In addition, pyramiding WSC favorable alleles was not only effective for
      obtaining accessions with higher WSC, but also for enhancing TGW under different
      water regimes. During the past fifty years of wheat breeding, WSC was selected
      incidentally. The average number of favorable WSC alleles increased from 1.13 in
      the pre-1960 period to 4.41 in the post-2000 period. The results indicate a high
      potential for using marker-assisted selection to pyramid WSC favorable alleles in
      improving WSC and TGW in wheat. 

PMID- 25768727
TI  - Genetic structure of Daphnia galeata populations in Eastern China.
AB  - This study presents the first examination of the genetic structure of Daphnia
      longispina complex populations in Eastern China. Only one species, D. galeata,
      was present across the eight investigated lakes; as identified by taxon
      assignment using allelic variation at 15 microsatellite loci. Three genetically
      differentiated D. galeata subgroups emerged independent of the type of
      statistical analysis applied. Thus, Bayesian clustering, discriminant analysis
      based on results from factorial correspondence analysis, and UPGMA clustering
      consistently showed that populations from two neighbouring lakes were genetically
      separated from a mixture of genotypes found in other lakes, which formed another
      two subgroups. Clonal diversity was high in all D. galeata populations, and most
      samples showed no deviation from Hardy-Weinberg equilibrium, indicating that
      clonal selection had little effect on the genetic diversity. Overall, populations
      did not cluster by geographical origin. Further studies will show if the observed
      pattern can be explained by natural colonization processes or by recent
      anthropogenic impact on predominantly artificial lakes.

PMID- 25768728
TI  - Fishery induces sperm depletion and reduction in male reproductive potential for
      crab species under male-biased harvest strategy.
AB  - Sperm depletion in males can occur when polygynous species are intensively
      exploited under a male-biased management strategy. In fisheries involving crabs
      species, the effects of this type of management on the reproductive potential is
      far from being understood. This study tests whether male-biased management of the
      principal Chilean crab fishery is able to affect the potential capacity of
      Metacarcinus edwardsii males to transfer sperm to females. Five localities in
      southern Chile, recording contrasting crab fishery landing, were selected to
      assess the potential of sperm depletion triggered by fishery. Seasonally, male
      crabs from each locality were obtained. Dry weight and histological condition of
      vasa deferentia and the Vaso-Somatic Index (VSI) were determined in order to use
      them as proxies for sperm depletion and male reproductive condition. A
      manipulative experiment was performed in the laboratory to estimate vasa
      deferentia weight and VSI from just-mated males in order to obtain a reference
      point for the potential effects of the fishery on sperm reserves. Sperm storage
      capacity is significantly affected by fisheries; during the mating season vasa
      deferentia from localities with low fishery intensity were heavier than those
      from high intensity fisheries, and these differences were even more evident in
      large males. Histological section showed that this disparity in vasa deferentia
      weight was explained principally by differences in the quantity of spermatophores
      rather than other seminal material. VSI was always higher in males from
      localities with low fishery intensity. Males from localities with high fishery
      intensity showed little capacity to recover sperm reserves and the VSI of these
      males remained below the values of the just-mated males. Detriment in the
      capacity of males to transfer sperm is the first step to sperm limitation in an
      exploited population, thus detection of sperm depletion can be an alert to
      introduce changes in the current management of crabs. 

PMID- 25768729
TI  - Elucidating the Role of Site-Specific Nitration of alpha-Synuclein in the
      Pathogenesis of Parkinson's Disease via Protein Semisynthesis and Mutagenesis.
AB  - Parkinson's disease (PD) is characterized by the loss of dopaminergic neurons in
      the substantia nigra and the presence of intraneuronal inclusions consisting of
      aggregated and post-translationally modified alpha-synuclein (alpha-syn). Despite
      advances in the chemical synthesis of alpha-syn and other proteins, the
      generation of site-specifically nitrated synthetic proteins has not been
      reported. Consequently, it has not been possible to determine the roles of
      nitration at specific residues in regulating the physiological and pathogenic
      properties of alpha-syn. Here we report, for the first time, the site-specific
      incorporation of 3-nitrotyrosine at different regions of alpha-syn using native
      chemical ligation combined with a novel desulfurization strategy. This strategy
      enabled us to investigate the role of nitration at single or multiple tyrosine
      residues in regulating alpha-syn structure, membrane binding, oligomerization,
      and fibrils formation. We demonstrate that different site-specifically nitrated
      alpha-syn species exhibit distinct structural and aggregation properties and
      exhibit reduced affinity to negatively charged vesicle membranes. We provide
      evidence that intermolecular interactions between the N- and C-terminal regions
      of alpha-syn play critical roles in mediating nitration-induced alpha-syn
      oligomerization. For example, when Y39 is not available for nitration (Y39F and
      Y39/125F), the extent of cross-linking is limited mostly to dimer formation,
      whereas mutants in which Y39 along with one or multiple C-terminal tyrosines
      (Y125F, Y133F, Y136F and Y133/136F) can still undergo nitration readily to form
      higher-order oligomers. Our semisynthetic strategy for generating site
      specifically nitrated proteins opens up new possibilities for investigating the
      role of nitration in regulating protein structure and function in health and
      disease. 

PMID- 25768730
TI  - Preferential recruitment of Th17 cells to cervical cancer via CCR6-CCL20 pathway.
AB  - Our previous studies suggest that Th17 cells accumulate within tumor tissues and
      correlate with recurrence of cervical cancer patients. However, the source of the
      increased tumor-infiltrating Th17 cells remains poorly understood. We
      investigated the prevalence, phenotype and trafficking property of Th17 cells in
      patients with cervical cancer. Our results showed that Th17 cells highly
      aggregated within tumor tissues in an activated phenotype with markedly increased
      expression of CCR6. Correspondingly, level of CCL20 in the tumor tissues was
      significantly higher than that in non-tumor and normal control tissues, and
      strongly positively associated with Th17 cells. Further, in vitro migration assay
      showed CCL20 had effective chemotaxis to circulating Th17 cells. In conclusion,
      Th17 cells are recruited into tumor tissues preferentially through CCR6-CCL20
      pathway, which can serve as a novel therapeutic target for cervical cancer. 

PMID- 25768731
TI  - Balance impairment in patients with COPD.
AB  - BACKGROUND/PURPOSE: Chronic obstructive pulmonary disease (COPD) is a respiratory
      disease that results in progressive airflow limitation and respiratory distress.
      Physiopathological features of COPD suggest that people who suffer from this
      disease have many risk factors for falls that have been identified in older
      individuals. The aim of the study was to compare and quantify functional balance
      between COPD patients and healthy subjects; to investigate the risk of falls in
      acute stages of the disease and to identify risk factors that could lead to
      falls. METHODS: We studied 46 patients with moderate-severe COPD (29 stable and
      17 in acute exacerbation--AECOPD) and 17 healthy subjects (control group) having
      similar demographic data. We analyzed the difference in Berg Balance Scale (BBS),
      Single Leg Stance (SLS) and Timed Up and Go test (TUG) between these three groups
      and the correlation of these scores with a number of incriminatory factors.
      RESULTS: The presence of COPD was associated with significant worsening of
      balance tests: BBS (55 control, vs. 53 COPD, vs. 44 AECOPD points p<0.001), TUG
      (8.6 control vs. 12.3 COPD vs. 15.9 AECOPD seconds. p<0.001), SLS (31.1 control
      vs. 17.7 COPD vs. 7.2 AECOPD seconds p<0.001) which may be associated with an
      increased risk of falls. Anxiety and depression were significantly associated
      with decreased balance test scores; anxiety (2 control vs. 6 COPD vs. 9 AECOPD
      points p<0.001) depression (2 control vs. 7 COPD vs. 12 AECOPD points p<0.001).
      CONCLUSIONS: According to our results COPD patients in moderate-severe stages and
      especially those in exacerbation have a high risk of falls.

PMID- 25768732
TI  - Relationship between heat-labile enterotoxin secretion capacity and virulence in
      wild type porcine-origin enterotoxigenic Escherichia coli strains.
AB  - Heat-labile enterotoxin (LT) is an important virulence factor secreted by some
      strains of enterotoxigenic Escherichia coli (ETEC). The prototypic human-origin
      strain H10407 secretes LT via a type II secretion system (T2SS). We sought to
      determine the relationship between the capacity to secrete LT and virulence in
      porcine-origin wild type (WT) ETEC strains. Sixteen WT ETEC strains isolated from
      cases of severe diarrheal disease were analyzed by GM1ganglioside enzyme-linked
      immunosorbent assay to measure LT concentrations in culture supernatants. All
      strains had detectable LT in supernatants by 2 h of culture and 1 strain, which
      was particularly virulent in gnotobiotic piglets (3030-2), had the highest LT
      secretion level all porcine-origin WT strains tested (P<0.05). The level of LT
      secretion (concentration in supernatants at 6-h culture) explained 92% of the
      variation in time-to-a-moribund-condition (R2 = 0.92, P<0.0001) in gnotobiotic
      piglets inoculated with either strain 3030-2, or an ETEC strain of lesser
      virulence (2534-86), or a non-enterotoxigenic WT strain (G58-1). All 16 porcine
      ETEC strains were positive by PCR analysis for the T2SS genes, gspD and gspK, and
      bioinformatic analysis of 4 porcine-origin strains for which complete genomic
      sequences were available revealed a T2SS with a high degree of homology to that
      of H10407. Maximum Likelihood phylogenetic trees constructed using T2SS genes
      gspC, gspD, gspE and homologs showed that strains 2534-86 and 3030-2 clustered
      together in the same clade with other porcine-origin ETEC strains in the
      database, UMNK88 and UMN18. Protein modeling of the ATPase gene (gspE) further
      revealed a direct relationship between the predicted ATP-binding capacities and
      LT secretion levels as follows: H10407, -8.8 kcal/mol and 199 ng/ml; 3030-2, -8.6
      kcal/mol and 133 ng/ml; and 2534-86, -8.5 kcal/mol and 80 ng/ml. This study
      demonstrated a direct relationship between predicted ATP-binding capacity of GspE
      and LT secretion, and between the latter and virulence. 

PMID- 25768733
TI  - Improving target coverage and organ-at-risk sparing in intensity-modulated
      radiotherapy for cervical oesophageal cancer using a simple optimisation method.
AB  - PURPOSE: To assess the performance of a simple optimisation method for improving
      target coverage and organ-at-risk (OAR) sparing in intensity-modulated
      radiotherapy (IMRT) for cervical oesophageal cancer. METHODS: For 20 selected
      patients, clinically acceptable original IMRT plans (Original plans) were
      created, and two optimisation methods were adopted to improve the plans: 1) a
      base dose function (BDF)-based method, in which the treatment plans were re
      optimised based on the original plans, and 2) a dose-controlling structure (DCS)
      based method, in which the original plans were re-optimised by assigning
      additional constraints for hot and cold spots. The Original, BDF-based and DCS
      based plans were compared with regard to target dose homogeneity, conformity, OAR
      sparing, planning time and monitor units (MUs). Dosimetric verifications were
      performed and delivery times were recorded for the BDF-based and DCS-based plans.
      RESULTS: The BDF-based plans provided significantly superior dose homogeneity and
      conformity compared with both the DCS-based and Original plans. The BDF-based
      method further reduced the doses delivered to the OARs by approximately 1-3%. The
      re-optimisation time was reduced by approximately 28%, but the MUs and delivery
      time were slightly increased. All verification tests were passed and no
      significant differences were found. CONCLUSION: The BDF-based method for the
      optimisation of IMRT for cervical oesophageal cancer can achieve significantly
      better dose distributions with better planning efficiency at the expense of
      slightly more MUs.

PMID- 25768734
TI  - Involvement of CX3CL1/CX3CR1 signaling in spinal long term potentiation.
AB  - The long-term potentiation (LTP) of spinal C-fiber-evoked field potentials is
      considered as a fundamental mechanism of central sensitization in the spinal
      cord. Accumulating evidence has showed the contribution of spinal microglia to
      spinal LTP and pathological pain. As a key signaling of neurons-microglia
      interactions, the involvement of CX3CL1/CX3CR1 signaling in pathological pain has
      also been investigated extensively. The present study examined whether
      CX3CL1/CX3CR1 signaling plays a role in spinal LTP. The results showed that 10
      trains tetanic stimulation (100 Hz, 2s) of the sciatic nerve (TSS) produced a
      significant LTP of C-fiber-evoked field potentials lasting for over 3 h in the
      rat spinal dorsal horn. Blockade of CX3CL1/CX3CR1 signaling with an anti-CX3CR1
      neutralizing antibody (CX3CR1 AB) markedly suppressed TSS-induced LTP. Exogenous
      CX3CL1 significantly potentiated 3-trains TSS-induced LTP in rats. Consistently,
      spinal LTP of C-fiber-evoked field potentials was also induced by TSS (100 Hz,
      1s, 4 trains) in all C57BL/6 wild type (WT) mice. However, in CX3CR1-/- mice, TSS
      failed to induce LTP and behavioral hypersensitivity, confirming an essential
      role of CX3CR1 in spinal LTP induction. Furthermore, blockade of IL-18 or IL-23,
      the potential downstream factors of CX3CL1/CX3CR1 signaling, with IL-18 BP or
      anti-IL-23 neutralizing antibody (IL-23 AB), obviously suppressed spinal LTP in
      rats. These results suggest that CX3CL1/CX3CR1 signaling is involved in LTP of C
      fiber-evoked field potentials in the rodent spinal dorsal horn. 

PMID- 25768735
TI  - Long-term effects of interprofessional biopsychosocial rehabilitation for adults
      with chronic non-specific low back pain: a multicentre, quasi-experimental study.
AB  - BACKGROUND: Improvement of the long-term effectiveness of multidisciplinary ortho
      paedic rehabilitation (MOR) in the management of chronic non-specific low back
      pain (CLBP) remains a central issue for health care in Germany. We developed an
      interprofessional and interdisciplinary, biopsychosocial rehabilitation concept
      named "PASTOR" to promote self-management in adults with CLBP and compared its
      effectiveness with the current model of MOR. METHODS: A multicentre quasi
      experimental study with three measurement time points was implemented. 680 adults
      aged 18 to 65 with CLBP were assed for eligibil-ity in three inpatient
      rehabilitation centres in Germany. At first the effects of the MOR, with a total
      extent of 48 hours (control group), were assessed. Thereafter, PASTOR was
      implemented and evaluated in the same centres (intervention group). It consisted
      of six interprofessional modules, which were provided on 12 days in fixed groups,
      with a total extent of 48 hours. Participants were assessed with self-report
      measures at baseline, discharge, and 12 months for functional ability (primary
      outcome) using the Hannover Functional Ability Questionnaire (FFbH-R) and vari
      ous secondary outcomes (e.g. pain, health status, physical activity, pain coping,
      pain-related cognitions). RESULTS: In total 536 participants were consecutively
      assigned to PASTOR (n=266) or MOR (n=270). At 12 months, complete data of 368
      participants was available. The adjusted between-group difference in the FFbH-R
      at 12 months was 6.58 (95% CI 3.38 to 9.78) using complete data and 3.56 (95% CI
      0.45 to 6.67) using available da-ta, corresponding to significant small-to-medium
      effect sizes of d=0.42 (p<0.001) and d=0.10 (p=0.025) in favour of PASTOR.
      Further improvements in secondary out-comes were also observed in favour of
      PASTOR. CONCLUSION: The interprofessional and interdisciplinary, biopsychosocial
      rehabilita-tion program PASTOR shows some improvements of the long-term
      effectiveness of inpatient rehabilitation in the management of adults with CLBP.
      Further insights into mechanisms of action of complex intervention programs are
      required. TRIAL REGISTRATION: ClinicalTrials.gov NCT02056951.

PMID- 25768736
TI  - Effects of cold atmospheric plasma (CAP) on beta-defensins, inflammatory
      cytokines, and apoptosis-related molecules in keratinocytes in vitro and in vivo.
AB  - Cold atmospheric plasma (CAP) has been gaining increasing interest as a new
      approach for the treatment of skin diseases or wounds. Although this approach has
      demonstrated promising antibacterial activity, its exact mechanism of action
      remains unclear. This study explored in vitro and in vivo whether CAP influences
      gene expression and molecular mechanisms in keratinocytes. Our results revealed
      that a 2 min CAP treatment using the MicroPlaSter beta in analogy to the
      performed clinical studies for wound treatment induces expression of IL-8, TGF
      beta1, and TGF-beta2. In vitro and in vivo assays indicated that keratinocyte
      proliferation, migration, and apoptotic mechanisms were not affected by the CAP
      treatment under the applied conditions. Further, we observed that antimicrobial
      peptides of the beta-defensin family are upregulated after CAP treatment. In
      summary, our results suggest that a 2 min application of CAP induces gene
      expression of key regulators important for inflammation and wound healing without
      causing proliferation, migration or cell death in keratinocytes. The induction of
      beta-defensins in keratinocytes describes an absolutely new plasma strategy.
      Activation of antimicrobial peptides supports the well-known antibacterial effect
      of CAP treatment, whereas the mechanism of beta-defensin activation by CAP is not
      investigated so far. 

PMID- 25768738
TI  - Tensor representation of spin States.
AB  - We propose a generalization of the Bloch sphere representation for arbitrary spin
      states. It provides a compact and elegant representation of spin density matrices
      in terms of tensors that share the most important properties of Bloch vectors.
      Our representation, based on covariant matrices introduced by Weinberg in the
      context of quantum field theory, allows for a simple parametrization of coherent
      spin states, and a straightforward transformation of density matrices under local
      unitary and partial tracing operations. It enables us to provide a criterion for
      anticoherence, relevant in a broader context such as quantum polarization of
      light. 

PMID- 25768737
TI  - Birth prevalence of neural tube defects and orofacial clefts in India: a
      systematic review and meta-analysis.
AB  - BACKGROUND: In the last two decades, India has witnessed a substantial decrease
      in infant mortality attributed to infectious disease and malnutrition. However,
      the mortality attributed to birth defects remains constant. Studies on the
      prevalence of birth defects such as neural tube defects and orofacial clefts in
      India have reported inconsistent results. Therefore, we conducted a systematic
      review of observational studies to document the birth prevalence of neural tube
      defects and orofacial clefts. METHODS: A comprehensive literature search for
      observational studies was conducted in MEDLINE and EMBASE databases using key
      MeSH terms (neural tube defects OR cleft lip OR cleft palate AND Prevalence AND
      India). Two reviewers independently reviewed the retrieved studies, and studies
      satisfying the eligibility were included. The quality of included studies was
      assessed using selected criteria from STROBE statement. RESULTS: The overall
      pooled birth prevalence (random effect) of neural tube defects in India is 4.5
      per 1000 total births (95% CI 4.2 to 4.9). The overall pooled birth prevalence
      (random effect) of orofacial clefts is 1.3 per 1000 total births (95% CI 1.1 to
      1.5). Subgroup analyses were performed by region, time period, consanguinity, and
      gender of newborn. CONCLUSION: The overall prevalence of neural tube defects from
      India is high compared to other regions of the world, while that of orofacial
      clefts is similar to other countries. The majority of studies included in the
      review were hospital based. The quality of these studies ranged from low to
      moderate. Further well-designed, high quality community-based observational
      studies are needed to accurately estimate the burden of neural tube defects and
      orofacial clefts in India.

PMID- 25768739
TI  - Two fermions in a double well: exploring a fundamental building block of the
      Hubbard model.
AB  - We have prepared two ultracold fermionic atoms in an isolated double-well
      potential and obtained full control over the quantum state of this system. In
      particular, we can independently control the interaction strength between the
      particles, their tunneling rate between the wells and the tilt of the potential.
      By introducing repulsive (attractive) interparticle interactions we have realized
      the two-particle analog of a Mott-insulating (charge-density-wave) state. We have
      also spectroscopically observed how second-order tunneling affects the energy of
      the system. This work realizes the first step of a bottom-up approach to
      deterministically create a single-site addressable realization of a ground-state
      Fermi-Hubbard system. 

PMID- 25768740
TI  - Systematic errors in current quantum state tomography tools.
AB  - Common tools for obtaining physical density matrices in experimental quantum
      state tomography are shown here to cause systematic errors. For example, using
      maximum likelihood or least squares optimization to obtain physical estimates for
      the quantum state, we observe a systematic underestimation of the fidelity and an
      overestimation of entanglement. Such strongly biased estimates can be avoided
      using linear evaluation of the data or by linearizing measurement operators
      yielding reliable and computational simple error bounds. 

PMID- 25768741
TI  - High-contrast qubit interactions using multimode cavity QED.
AB  - We introduce a new multimode cavity QED architecture for superconducting circuits
      that can be used to implement photonic memories, more efficient Purcell filters,
      and quantum simulations of photonic materials. We show that qubit interactions
      mediated by multimode cavities can have exponentially improved contrast for two
      qubit gates without sacrificing gate speed. Using two qubits coupled via a three
      mode cavity system we spectroscopically observe multimode strong couplings up to
      102 MHz and demonstrate suppressed interactions off resonance of 10 kHz when the
      qubits are ~600  MHz detuned from the cavity resonance. We study Landau-Zener
      transitions in our multimode systems and demonstrate quasiadiabatic loading of
      single photons into the multimode cavity in 25 ns. We introduce an adiabatic gate
      protocol to realize a controlled-Z gate between the qubits in 95 ns and create a
      Bell state with 94.7% fidelity. This corresponds to an on/off ratio (gate
      contrast) of 1000. 

PMID- 25768742
TI  - Efficient synthesis of universal repeat-until-success quantum circuits.
AB  - Recently it was shown that the resources required to implement unitary operations
      on a quantum computer can be reduced by using probabilistic quantum circuits
      called repeat-until-success (RUS) circuits. However, the previously best-known
      algorithm to synthesize a RUS circuit for a given target unitary requires
      exponential classical runtime. We present a probabilistically polynomial-time
      algorithm to synthesize a RUS circuit to approximate any given single-qubit
      unitary to precision epsilon over the Clifford+T basis. Surprisingly, the T count
      of the synthesized RUS circuit surpasses the theoretical lower bound of 3
      log_{2}(1/epsilon) that holds for purely unitary single-qubit circuit
      decomposition. By taking advantage of measurement and an ancilla qubit, RUS
      circuits achieve an expected T count of 1.15 log_{2}(1/epsilon) for single-qubit
      z rotations. Our method leverages the fact that the set of unitaries
      implementable by RUS protocols has a higher density in the space of all unitaries
      compared to the density of purely unitary implementations. 

PMID- 25768744
TI  - Exact overlaps in the Kondo problem.
AB  - It is well known that the ground states of a Fermi liquid with and without a
      single Kondo impurity have an overlap that decays as a power law of the system
      size, expressing the Anderson orthogonality catastrophe. Ground states with two
      different values of the Kondo couplings have, however, a finite overlap in the
      thermodynamic limit. This overlap, which plays an important role in quantum
      quenches for impurity systems, is a universal function of the ratio of the
      corresponding Kondo temperatures, which is not accessible using perturbation
      theory or the Bethe ansatz. Using a strategy based on the integrable structure of
      the corresponding quantum field theory, we propose an exact formula for this
      overlap, which we check against extensive density matrix renormalization group
      calculations. 

PMID- 25768743
TI  - Microwave quantum illumination.
AB  - Quantum illumination is a quantum-optical sensing technique in which an entangled
      source is exploited to improve the detection of a low-reflectivity object that is
      immersed in a bright thermal background. Here, we describe and analyze a system
      for applying this technique at microwave frequencies, a more appropriate spectral
      region for target detection than the optical, due to the naturally occurring
      bright thermal background in the microwave regime. We use an electro
      optomechanical converter to entangle microwave signal and optical idler fields,
      with the former being sent to probe the target region and the latter being
      retained at the source. The microwave radiation collected from the target region
      is then phase conjugated and upconverted into an optical field that is combined
      with the retained idler in a joint-detection quantum measurement. The error
      probability of this microwave quantum-illumination system, or quantum radar, is
      shown to be superior to that of any classical microwave radar of equal
      transmitted energy. 

PMID- 25768745
TI  - Quantum thermodynamics: a nonequilibrium Green's function approach.
AB  - We establish the foundations of a nonequilibrium theory of quantum thermodynamics
      for noninteracting open quantum systems strongly coupled to their reservoirs
      within the framework of the nonequilibrium Green's functions. The energy of the
      system and its coupling to the reservoirs are controlled by a slow external time
      dependent force treated to first order beyond the quasistatic limit. We derive
      the four basic laws of thermodynamics and characterize reversible
      transformations. Stochastic thermodynamics is recovered in the weak coupling
      limit. 

PMID- 25768746
TI  - Turbulent black holes.
AB  - We demonstrate that rapidly spinning black holes can display a new type of
      nonlinear parametric instability-which is triggered above a certain perturbation
      amplitude threshold-akin to the onset of turbulence, with possibly observable
      consequences. This instability transfers from higher temporal and azimuthal
      spatial frequencies to lower frequencies-a phenomenon reminiscent of the inverse
      cascade displayed by (2+1)-dimensional fluids. Our finding provides evidence for
      the onset of transitory turbulence in astrophysical black holes and predicts
      observable signatures in black hole binaries with high spins. Furthermore, it
      gives a gravitational description of this behavior which, through the fluid
      gravity duality, can potentially shed new light on the remarkable phenomena of
      turbulence in fluids. 

PMID- 25768747
TI  - Orbital resonances around black holes.
AB  - We compute the length and time scales associated with resonant orbits around Kerr
      black holes for all orbital and spin parameters. Resonance-induced effects are
      potentially observable when the Event Horizon Telescope resolves the inner
      structure of Sgr A*, when space-based gravitational wave detectors record phase
      shifts in the waveform during the resonant passage of a compact object spiraling
      into the black hole, or in the frequencies of quasiperiodic oscillations for
      accreting black holes. The onset of geodesic chaos for non-Kerr spacetimes should
      occur at the resonance locations quantified here. 

PMID- 25768748
TI  - Effective potentials and morphological transitions for binary black hole spin
      precession.
AB  - We derive an effective potential for binary black hole (BBH) spin precession at
      second post-Newtonian order. This effective potential allows us to solve the
      orbit-averaged spin-precession equations analytically for arbitrary mass ratios
      and spins. These solutions are quasiperiodic functions of time: after a fixed
      period, the BBH spins return to their initial relative orientations and jointly
      precess about the total angular momentum by a fixed angle. Using these solutions,
      we classify BBH spin precession into three distinct morphologies between which
      BBHs can transition during their inspiral. We also derive a precession-averaged
      evolution equation for the total angular momentum that can be integrated on the
      radiation-reaction time and identify a new class of spin-orbit resonances that
      can tilt the direction of the total angular momentum during the inspiral. Our new
      results will help efforts to model and interpret gravitational waves from generic
      BBH mergers and predict the distributions of final spins and gravitational
      recoils. 

PMID- 25768749
TI  - Gravitational Casimir effect.
AB  - We derive the gravitonic Casimir effect with nonidealized boundary conditions.
      This allows the quantification of the gravitonic contribution to the Casimir
      effect from real bodies. We quantify the meagerness of the gravitonic Casimir
      effect in ordinary matter. We also quantify the enhanced effect produced by the
      speculated Heisenberg-Couloumb (HC) effect in superconductors, thereby providing
      a test for the validity of the HC theory, and, consequently, the existence of
      gravitons. 

PMID- 25768751
TI  - Possible indication of momentum-dependent asymmetric dark matter in the sun.
AB  - Broad disagreement persists between helioseismological observables and
      predictions of solar models computed with the latest surface abundances. Here we
      show that most of these problems can be solved by the presence of asymmetric dark
      matter coupling to nucleons as the square of the momentum q exchanged in the
      collision. We compute neutrino fluxes, small frequency separations, surface
      helium abundances, sound speed profiles, and convective zone depths for a number
      of models, showing more than a 6sigma preference for q^{2} models over others,
      and over the standard solar model. The preferred mass (3 GeV) and reference dark
      matter-nucleon cross section (10^{-37}  cm^{2} at q_{0}=40  MeV) are within the
      region of parameter space allowed by both direct detection and collider searches.

PMID- 25768753
TI  - Simulation of black hole collisions in asymptotically Anti-de Sitter spacetimes.
AB  - We present results from the evolution of spacetimes that describe the merger of
      asymptotically global anti-de Sitter black holes in 5D with an SO(3) symmetry.
      Prompt scalar field collapse provides us with a mechanism for producing distinct
      trapped regions on the initial slice, associated with black holes initially at
      rest. We evolve these black holes towards a merger, and follow the subsequent
      ring down. The boundary stress tensor of the dual conformal field theory is
      conformally related to a stress tensor in Minkowski space that inherits an axial
      symmetry from the bulk SO(3). We compare this boundary stress tensor to its
      hydrodynamic counterpart with viscous corrections of up to second order, and
      compare the conformally related stress tensor to ideal hydrodynamic simulations
      in Minkowski space, initialized at various time slices of the boundary data. Our
      findings reveal far-from-hydrodynamic behavior at early times, with a transition
      to ideal hydrodynamics at late times. 

PMID- 25768752
TI  - Observing inflationary reheating.
AB  - Reheating is the epoch which connects inflation to the subsequent hot big-bang
      phase. Conceptually very important, this era is, however, observationally poorly
      known. We show that the current Planck satellite measurements of the cosmic
      microwave background (CMB) anisotropies constrain the kinematic properties of the
      reheating era for most of the inflationary models. This result is obtained by
      deriving the marginalized posterior distributions of the reheating parameter for
      about 200 models of slow-roll inflation. Weighted by the statistical evidence of
      each model to explain the data, we show that the Planck 2013 measurements induce
      an average reduction of the posterior-to-prior volume by 40%. Making some
      additional assumptions on reheating, such as specifying a mean equation of state
      parameter, or focusing the analysis on peculiar scenarios, can enhance or reduce
      this constraint. Our study also indicates that the Bayesian evidence of a model
      can substantially be affected by the reheating properties. The precision of the
      current CMB data is therefore such that estimating the observational performance
      of a model now requires incorporating information about its reheating history. 

PMID- 25768750
TI  - Constraints on an annihilation signal from a core of constant dark matter density
      around the milky way center with H.E.S.S.
AB  - An annihilation signal of dark matter is searched for from the central region of
      the Milky Way. Data acquired in dedicated on-off observations of the Galactic
      center region with H.E.S.S. are analyzed for this purpose. No significant signal
      is found in a total of ~9  h of on-off observations. Upper limits on the velocity
      averaged cross section, ?sigmav?, for the annihilation of dark matter particles
      with masses in the range of ~300  GeV to ~10  TeV are derived. In contrast to
      previous constraints derived from observations of the Galactic center region, the
      constraints that are derived here apply also under the assumption of a central
      core of constant dark matter density around the center of the Galaxy. Values of
      ?sigmav? that are larger than 3*10^{-24}  cm^{3}/s are excluded for dark matter
      particles with masses between ~1 and ~4  TeV at 95% C.L. if the radius of the
      central dark matter density core does not exceed 500 pc. This is the strongest
      constraint that is derived on ?sigmav? for annihilating TeV mass dark matter
      without the assumption of a centrally cusped dark matter density distribution in
      the search region. 

PMID- 25768754
TI  - Study of CP asymmetry in B^{0}-B[over -]^{0} mixing with inclusive dilepton
      events.
AB  - We present a measurement of the asymmetry A_{CP} between same-sign inclusive
      dilepton samples l^{+}l^{+} and l^{-}l^{-} (l=e, MU) from semileptonic B decays
      in Upsilon(4S)->BB[over -] events, using the complete data set recorded by the
      BABAR experiment near the Upsilon(4S) resonance, corresponding to 471*10^{6}
      BB[over -] pairs. The asymmetry A_{CP} allows comparison between the mixing
      probabilities P(B[over -]^{0}->B^{0}) and P(B^{0}->B[over -]^{0}), and therefore
      probes CP and T violation. The result, A_{CP}=[-3.9+/-3.5(stat)+/-1.9(syst)]*10^{
      3}, is consistent with the standard model expectation. 

PMID- 25768756
TI  - Static quark-antiquark potential in the quark-gluon plasma from lattice QCD.
AB  - We present a state-of-the-art determination of the complex valued static quark
      antiquark potential at phenomenologically relevant temperatures around the
      deconfinement phase transition. Its values are obtained from nonperturbative
      lattice QCD simulations using spectral functions extracted via a novel Bayesian
      inference prescription. We find that the real part, both in a gluonic medium, as
      well as in realistic QCD with light u, d, and s quarks, lies close to the color
      singlet free energies in Coulomb gauge and shows Debye screening above the
      (pseudo)critical temperature T_{c}. The imaginary part is estimated in the
      gluonic medium, where we find that it is of the same order of magnitude as in
      hard-thermal loop resummed perturbation theory in the deconfined phase. 

PMID- 25768758
TI  - Ballistic protons in incoherent exclusive vector meson production as a measure of
      rare parton fluctuations at an electron-ion collider.
AB  - We argue that the proton multiplicities measured in Roman pot detectors at an
      electron ion collider can be used to determine centrality classes in incoherent
      diffractive scattering. Incoherent diffraction probes the fluctuations in the
      interaction strengths of multiparton Fock states in the nuclear wave functions.
      In particular, the saturation scale that characterizes this multiparton dynamics
      is significantly larger in central events relative to minimum bias events. As an
      application, we study the centrality dependence of incoherent diffractive vector
      meson production. We identify an observable which is simultaneously very
      sensitive to centrality triggered parton fluctuations and insensitive to details
      of the model. 

PMID- 25768757
TI  - New limits on intrinsic charm in the nucleon from global analysis of parton
      distributions.
AB  - We present a new global QCD analysis of parton distribution functions, allowing
      for possible intrinsic charm (IC) contributions in the nucleon inspired by light
      front models. The analysis makes use of the full range of available high-energy
      scattering data for Q^{2}?1  GeV^{2} and W^{2}?3.5  GeV^{2}, including fixed
      target proton and deuteron cross sections at lower energies that were excluded in
      previous global analyses. The expanded data set places more stringent constraints
      on the momentum carried by IC, with ?x?_{IC} at most 0.5% (corresponding to an IC
      normalization of ~1%) at the 4sigma level for Deltachi^{2}=1. We also critically
      assess the impact of older EMC measurements of F_{2}^{c} at large x, which favor
      a nonzero IC, but with very large chi^{2} values. 

PMID- 25768760
TI  - Power counting of contact-range currents in effective field theory.
AB  - We analyze the power counting of two-body currents in nuclear effective field
      theories (EFTs). We find that the existence of nonperturbative physics at low
      energies, which is manifest in the existence of the deuteron and the ^{1}S_{0} NN
      virtual bound state, combined with the appearance of singular potentials in
      versions of nuclear EFT that incorporate chiral symmetry, modifies the
      renormalization-group flow of the couplings associated with contact operators
      that involve nucleon-nucleon pairs and external fields. The order of these
      couplings is thereby enhanced with respect to the naive-dimensional-analysis
      estimate. Consequently, short-range currents enter at a lower order in the chiral
      EFT than has been appreciated up until now, and their impact on low-energy
      observables is concomitantly larger. We illustrate the changes in the power
      counting with a few low-energy processes involving external probes and few
      nucleon systems, including electron-deuteron elastic scattering and radiative
      neutron capture by protons. 

PMID- 25768761
TI  - Tunneling dynamics in multiphoton ionization and attoclock calibration.
AB  - The intermediate domain of strong-field ionization between the tunneling and
      multiphoton regimes is investigated using the strong-field approximation and the
      imaginary-time method. An intuitive model for the dynamics is developed which
      describes the ionization process within a nonadiabatic tunneling picture with a
      coordinate dependent electron energy during the under-the-barrier motion. The
      nonadiabatic effects in the elliptically polarized laser field induce a
      transversal momentum shift of the tunneled electron wave packet at the tunnel
      exit and a delayed appearance in the continuum as well as a shift of the
      tunneling exit towards the ionic core. The latter significantly modifies the
      Coulomb focusing during the electron excursion in the laser field after exiting
      the ionization tunnel. We show that nonadiabatic effects are especially large
      when the Coulomb field of the ionic core is taken into account during the under
      the-barrier motion. The simple man model modified with these nonadiabatic
      corrections provides an intuitive background for exact theories and has direct
      implications for the calibration of the attoclock technique. 

PMID- 25768762
TI  - Disorder-induced localization in a strongly correlated atomic Hubbard gas.
AB  - We observe the emergence of a disorder-induced insulating state in a strongly
      interacting atomic Fermi gas trapped in an optical lattice. This closed quantum
      system, free of a thermal reservoir, realizes the disordered Fermi-Hubbard model,
      which is a minimal model for strongly correlated electronic solids. We observe
      disorder-induced localization of a metallic state through measurements of mass
      transport. By varying the lattice potential depth, we detect interaction-driven
      delocalization of the disordered insulating state. We also measure localization
      that persists as the temperature of the gas is raised. These behaviors are
      consistent with many-body localization, which is a novel paradigm for
      understanding localization in interacting quantum systems at nonzero temperature.

PMID- 25768759
TI  - Transverse wobbling in ^{135}pr.
AB  - A pair of transverse wobbling bands is observed in the nucleus ^{135}Pr. The
      wobbling is characterized by DeltaI=1, E2 transitions between the bands, and a
      decrease in the wobbling energy confirms its transverse nature. Additionally, a
      transition from transverse wobbling to a three-quasiparticle band comprised of
      strong magnetic dipole transitions is observed. These observations conform well
      to results from calculations with the tilted axis cranking model and the
      quasiparticle rotor model. 

PMID- 25768763
TI  - Theory for the spatiotemporal dynamics of domain walls close to a nonequilibrium
      Ising-Bloch transition.
AB  - We derive a generic model for the interaction of domain walls close to a
      nonequilibrium-Bloch transition. The universal scenario predicted by the model
      includes stationary Ising and Bloch localized structures (dissipative solitons),
      as well as drifting and oscillating Bloch structures. Our theory also explains
      the behavior of Bloch walls during a collision. The results are confirmed by
      numerical simulations of the Ginzburg-Landau equation forced at twice its natural
      frequency and are in agreement with previous observations in several physical
      systems. 

PMID- 25768764
TI  - Reduction of SO(2) symmetry for spatially extended dynamical systems.
AB  - Spatially extended systems, such as channel or pipe flows, are often equivariant
      under continuous symmetry transformations, with each state of the flow having an
      infinite number of equivalent solutions obtained from it by a translation or a
      rotation. This multitude of equivalent solutions tends to obscure the dynamics of
      turbulence. Here we describe the "first Fourier mode slice," a very simple, easy
      to implement reduction of SO(2) symmetry. While the method exhibits rapid
      variations in phase velocity whenever the magnitude of the first Fourier mode is
      nearly vanishing, these near singularities can be regularized by a time-scaling
      transformation. We show that after application of the method, hitherto unseen
      global structures, for example, Kuramoto-Sivashinsky relative periodic orbits and
      unstable manifolds of traveling waves, are uncovered. 

PMID- 25768765
TI  - Multichromatic narrow-energy-spread electron bunches from laser-wakefield
      acceleration with dual-color lasers.
AB  - A method based on laser wakefield acceleration with controlled ionization
      injection triggered by another frequency-tripled laser is proposed, which can
      produce electron bunches with low energy spread. As two color pulses copropagate
      in the background plasma, the peak amplitude of the combined laser field is
      modulated in time and space during the laser propagation due to the plasma
      dispersion. Ionization injection occurs when the peak amplitude exceeds a certain
      threshold. The threshold is exceeded for limited duration periodically at
      different propagation distances, leading to multiple ionization injections and
      separated electron bunches. The method is demonstrated through multidimensional
      particle-in-cell simulations. Such electron bunches may be used to generate
      multichromatic x-ray sources for a variety of applications. 

PMID- 25768766
TI  - Suppression of laser nonuniformity imprinting using a thin high-z coating.
AB  - Imprinting of laser nonuniformity is a limiting factor in direct-drive inertial
      confinement fusion experiments, particularly when available laser smoothing is
      limited. A thin (~400  A) high-Z metal coating is found to substantially suppress
      laser imprint for planar targets driven by pulse shapes and intensities relevant
      to implosions on the National Ignition Facility while retaining low adiabat
      target acceleration. A hybrid of indirect and direct drive, this configuration
      results in initial ablation by x rays from the heated high-Z layer, creating a
      large standoff for perturbation smoothing. 

PMID- 25768767
TI  - Statistical simulation of the magnetorotational dynamo.
AB  - Turbulence and dynamo induced by the magnetorotational instability (MRI) are
      analyzed using quasilinear statistical simulation methods. It is found that
      homogenous turbulence is unstable to a large-scale dynamo instability, which
      saturates to an inhomogenous equilibrium with a strong dependence on the magnetic
      Prandtl number (Pm). Despite its enormously reduced nonlinearity, the dependence
      of the angular momentum transport on Pm in the quasilinear model is qualitatively
      similar to that of nonlinear MRI turbulence. This demonstrates the importance of
      the large-scale dynamo and suggests how dramatically simplified models may be
      used to gain insight into the astrophysically relevant regimes of very low or
      high Pm. 

PMID- 25768768
TI  - Simultaneous acceleration of protons and electrons at nonrelativistic
      quasiparallel collisionless shocks.
AB  - We study diffusive shock acceleration (DSA) of protons and electrons at
      nonrelativistic, high Mach number, quasiparallel, collisionless shocks by means
      of self-consistent 1D particle-in-cell simulations. For the first time, both
      species are found to develop power-law distributions with the universal spectral
      index -4 in momentum space, in agreement with the prediction of DSA. We find that
      scattering of both protons and electrons is mediated by right-handed circularly
      polarized waves excited by the current of energetic protons via nonresonant
      hybrid (Bell) instability. Protons are injected into DSA after a few gyrocycles
      of shock drift acceleration (SDA), while electrons are first preheated via SDA,
      then energized via a hybrid acceleration process that involves both SDA and Fermi
      like acceleration mediated by Bell waves, before eventual injection into DSA.
      Using the simulations we can measure the electron-proton ratio in accelerated
      particles, which is of paramount importance for explaining the cosmic ray fluxes
      measured on Earth and the multiwavelength emission of astrophysical objects such
      as supernova remnants, radio supernovae, and galaxy clusters. We find the
      normalization of the electron power law is ?10^{-2} of the protons for strong
      nonrelativistic shocks. 

PMID- 25768770
TI  - Wetting transition for carbon nanotube arrays under metal contacts.
AB  - Structural arrays with nanoscale spacing arise in many device concepts. Carbon
      nanotube transistors are an extreme example, where a practical technology will
      require arrays of parallel nanotubes with spacing of order 10 nm or less. We show
      that with decreasing pitch there is a first-order transition, from a robust
      structure in which the metal wets the substrate between tubes, to a poorly
      wetting structure in which the metal rides atop the nanotube array without
      touching the substrate. The latter is analogous to the superhydrophobic "lotus
      leaf effect." There is a sharp minimum in the delamination energy of metal
      contacts at the transition pitch. We discuss implications for contact resistance
      and possible mitigation strategies. 

PMID- 25768769
TI  - Finding the elusive E*B staircase in magnetized plasmas.
AB  - Turbulence in hot magnetized plasmas is shown to generate permeable localized
      transport barriers that globally organize into the so-called "ExB staircase" [G.
      Dif-Pradalier et al., Phys. Rev. E, 82, 025401(R) (2010)]. Its domain of
      existence and dependence with key plasma parameters is discussed theoretically.
      Based on these predictions, staircases are observed experimentally in the Tore
      Supra tokamak by means of high-resolution fast-sweeping X-mode reflectometry.
      This observation strongly emphasizes the critical role of mesoscale self
      organization in plasma turbulence and may have far-reaching consequences for
      turbulent transport models and their validation. 

PMID- 25768771
TI  - Pressure-induced valence crossover and novel metamagnetic behavior near the
      antiferromagnetic quantum phase transition of YbNi_{3}Ga_{9}.
AB  - We report electrical resistivity, ac magnetic susceptibility, and x-ray
      absorption spectroscopy measurements of intermediate valence YbNi_{3}Ga_{9} under
      pressure and magnetic field. We have revealed a characteristic pressure-induced
      Yb valence crossover within the temperature-pressure phase diagram, and a first
      order metamagnetic transition is found below P_{c}~9  GPa where the system
      undergoes a pressure-induced antiferromagnetic transition. As a possible origin
      of the metamagnetic behavior, a critical valence fluctuation emerging near the
      critical point of the first-order valence transition is discussed on the basis of
      the temperature-field-pressure phase diagram.

PMID- 25768772
TI  - Impact of electron-hole correlations on the 1T-TiSe_{2} electronic structure.
AB  - Several experiments have been performed on 1T-TiSe_{2} in order to identify
      whether the electronic structure is semimetallic or semiconducting without
      reaching a consensus. In this Letter, we theoretically study the impact of
      electron-hole and electron-phonon correlations on the bare semimetallic and
      semiconducting electronic structure. The resulting electron spectral functions
      provide a direct comparison of both cases and demonstrate that 1T-TiSe_{2} is of
      predominant semiconducting character with some spectral weight crossing the Fermi
      level. 

PMID- 25768773
TI  - Crossover from super- to subdiffusive motion and memory effects in crystalline
      organic semiconductors.
AB  - The transport properties at finite temperature of crystalline organic
      semiconductors are investigated, within the Su-Schrieffer-Heeger model, by
      combining an exact diagonalization technique, Monte Carlo approaches, and a
      maximum entropy method. The temperature-dependent mobility data measured in
      single crystals of rubrene are successfully reproduced: a crossover from super-
      to subdiffusive motion occurs in the range 150<=T<=200  K, where the mean free
      path becomes of the order of the lattice parameter and strong memory effects
      start to appear. We provide an effective model, which can successfully explain
      features of the absorption spectra at low frequencies. The observed response to
      slowly varying electric field is interpreted by means of a simple model where the
      interaction between the charge carrier and lattice polarization modes is
      simulated by a harmonic interaction between a fictitious particle and an electron
      embedded in a viscous fluid. 

PMID- 25768774
TI  - Oscillatory behavior of vortex-lattice melting transition line in mesoscopic
      Bi_{2}Sr_{2}CaCu_{2}O_{8+y} superconductors.
AB  - The vortex-lattice melting transition of a limited number of vortices confined in
      mesoscopic square superconductors was studied by c-axis resistance measurements
      using stacks of intrinsic Josephson junctions in Bi_{2}Sr_{2}CaCu_{2}O_{8+y}. In
      contrast to the melting transition in bulk crystals, we have first found a clear
      oscillatory behavior in the field dependence of the melting temperature in small
      samples of 5-10  MUm square. The periods of the oscillations roughly obey the
      regularity of the matching conditions of square vortex lattices surrounded by a
      square boundary and the melting temperatures are enhanced around the vortex
      number of i^{2} (where i is an integer). The results suggest that a confinement
      effect by the square boundary stabilizes square lattice structures which are
      realized around i^{2} vortex number even in competition with the favorable
      Abrikosov triangular lattice in the bulk. 

PMID- 25768775
TI  - Surface aligned magnetic moments and hysteresis of an endohedral single-molecule
      magnet on a metal.
AB  - The interaction between the endohedral unit in the single-molecule magnet
      Dy_{2}ScN@C_{80} and a rhodium (111) substrate leads to alignment of the Dy 4f
      orbitals. The resulting orientation of the Dy_{2}ScN plane parallel to the
      surface is inferred from comparison of the angular anisotropy of x-ray absorption
      spectra and multiplet calculations in the corresponding ligand field. The x-ray
      magnetic circular dichroism is also angle dependent and signals strong
      magnetocrystalline anisotropy. This directly relates geometric and magnetic
      structure. Element specific magnetization curves from different coverages exhibit
      hysteresis at a sample temperature of ~4  K. From the measured hysteresis curves,
      we estimate the zero field remanence lifetime during x-ray exposure of a
      submonolayer to be about 30 seconds. 

PMID- 25768776
TI  - Magnetic moments of chromium-doped gold clusters: the Anderson impurity model in
      finite systems.
AB  - The magnetic moment of a single impurity atom in a finite free electron gas is
      studied in a combined x-ray magnetic circular dichroism spectroscopy, charge
      transfer multiplet calculation, and density functional theory study of size
      selected free chromium-doped gold clusters. The observed size dependence of the
      local magnetic moment can be understood as a transition from a local moment to a
      mixed valence regime. This shows that the Anderson impurity model essentially
      describes finite systems even though the discrete density of states introduces a
      significant deviation from a bulk metal, and the free electron gas is only formed
      by less than 10 electrons. Electronic shell closure in the gold host minimizes
      the interaction of localized impurity states with the confined free electron gas
      and preserves the magnetic moment of 5 MU_{B} fully in CrAu_{2}^{+} and almost
      fully in CrAu_{6}^{+}. Even for open-shell species, large local moments are
      observed that scale with the energy gap of the gold cluster. This indicates that
      an energy gap in the free electron gas stabilizes the local magnetic moment of
      the impurity atom. 

PMID- 25768777
TI  - Magnon-driven domain-wall motion with the Dzyaloshinskii-Moriya interaction.
AB  - We study domain-wall (DW) motion induced by spin waves (magnons) in the presence
      of the Dzyaloshinskii-Moriya interaction (DMI). The DMI exerts a torque on the DW
      when spin waves pass through the DW, and this torque represents a linear momentum
      exchange between the spin wave and the DW. Unlike angular momentum exchange
      between the DW and spin waves, linear momentum exchange leads to a rotation of
      the DW plane rather than a linear motion. In the presence of an effective easy
      plane anisotropy, this DMI induced linear momentum transfer mechanism is
      significantly more efficient than angular momentum transfer in moving the DW. 

PMID- 25768778
TI  - Hole properties on and off magnetization plateaus in 2D antiferromagnets.
AB  - The phenomenon of magnetization plateaus in antiferromagnets under a magnetic
      field has always been an important topic in magnetism. We propose to probe the
      elusive physics of plateaus in 2D by considering a hole-doped antiferromagnet and
      studying the signatures of magnetization plateaus in terms of the properties of
      holes, coupled to an effective gauge field generated by the spin sector. The
      latter mediates interaction between the holes, found to be algebraically decaying
      and long ranged with both Coulombic and dipolar forms outside the plateau and
      short ranged (local) inside the plateau. The resulting hole spectral weight is
      significantly broadened off plateau, while it remains sharply peaked on plateau.
      We also extend the result obtained for a 1D system where finite hole doping gives
      rise to a shift in the magnetization value of the plateaus. 

PMID- 25768779
TI  - Extracting the redox orbitals in Li battery materials with high-resolution x-ray
      compton scattering spectroscopy.
AB  - We present an incisive spectroscopic technique for directly probing redox
      orbitals based on bulk electron momentum density measurements via high-resolution
      x-ray Compton scattering. Application of our method to spinel Li_{x}Mn_{2}O_{4},
      a lithium ion battery cathode material, is discussed. The orbital involved in the
      lithium insertion and extraction process is shown to mainly be the oxygen 2p
      orbital. Moreover, the manganese 3d states are shown to experience spatial
      delocalization involving 0.16+/-0.05 electrons per Mn site during the battery
      operation. Our analysis provides a clear understanding of the fundamental redox
      process involved in the working of a lithium ion battery. 

PMID- 25768780
TI  - Intrinsic circular polarization in centrosymmetric stacks of transition-metal
      dichalcogenide compounds.
AB  - The circular polarization (CP) that the photoluminescence inherits from the
      excitation source in n monolayers of transition-metal dichalcogenides
      (MX_{2})_{n} has been previously explained as a special feature of odd values of
      n, where the inversion symmetry is absent. This "valley polarization" effect
      results from the fact that, in the absence of inversion symmetry, charge carriers
      in different band valleys could be selectively excited by different circular
      polarized light. Although several experiments observed CP in centrosymmetric
      MX_{2} systems, e.g., for bilayer MX_{2}, they were dismissed as being due to
      some extrinsic sample irregularities. Here we show that also for n=even, where
      inversion symmetry is present and valley polarization physics is strictly absent,
      such intrinsic selectivity in CP is to be expected on the basis of fundamental
      spin-orbit physics. First-principles calculations of CP predict significant
      polarization for n=2 bilayers: from 69% in MoS_{2} to 93% in WS_{2}. This
      realization could broaden the range of materials to be considered as CP sources. 

PMID- 25768781
TI  - Transition to chaos in random networks with cell-type-specific connectivity.
AB  - In neural circuits, statistical connectivity rules strongly depend on cell-type
      identity. We study dynamics of neural networks with cell-type-specific
      connectivity by extending the dynamic mean-field method and find that these
      networks exhibit a phase transition between silent and chaotic activity. By
      analyzing the locus of this transition, we derive a new result in random matrix
      theory: the spectral radius of a random connectivity matrix with block-structured
      variances. We apply our results to show how a small group of hyperexcitable
      neurons within the network can significantly increase the network's computational
      capacity by bringing it into the chaotic regime. 

PMID- 25768782
TI  - Pressure-driven suspension flow near jamming.
AB  - We report here magnetic resonance imaging measurements performed on suspensions
      with a bulk solid volume fraction (phi_{0}) up to 0.55 flowing in a pipe. We
      visualize and quantify spatial distributions of phi and velocity across the pipe
      at different axial positions. For dense suspensions (phi_{0}>0.5), we found a
      different behavior compared to the known cases of lower phi_{0}. Our experimental
      results demonstrate compaction within the jammed region (characterized by a zero
      macroscopic shear rate) from the jamming limit phi_{m}~0.58 at its outer boundary
      to the random close packing limit phi_{rcp}~0.64 at the center. Additionally, we
      show that phi and velocity profiles can be fairly well captured by a frictional
      rheology accounting for both further compaction of jammed regions as well as
      normal stress differences. 

PMID- 25768783
TI  - Snapshots of the fluctuating hydrogen bond network in liquid water on the sub
      femtosecond timescale with vibrational resonant inelastic x-ray scattering.
AB  - Liquid water molecules interact strongly with each other, forming a fluctuating
      hydrogen bond network and thereby giving rise to the anomalous phase diagram of
      liquid water. Consequently, symmetric and asymmetric water molecules have been
      found in the picosecond time average with IR and optical Raman spectroscopy. With
      subnatural linewidth resonant inelastic x-ray scattering (RIXS) at vibrational
      resolution, we take sub-femtosecond snapshots of the electronic and structural
      properties of water molecules in the hydrogen bond network. We derive a strong
      dominance of nonsymmetric molecules in liquid water in contrast to the gas phase
      on the sub-femtosecond timescale of RIXS and determine the fraction of highly
      asymmetrically distorted molecules. 

PMID- 25768784
TI  - Ionic current inversion in pressure-driven polymer translocation through
      nanopores.
AB  - We predict streaming current inversion with multivalent counterions in
      hydrodynamically driven polymer translocation events from a correlation-corrected
      charge transport theory including charge fluctuations around mean-field
      electrostatics. In the presence of multivalent counterions, electrostatic many
      body effects result in the reversal of the DNA charge. The attraction of anions
      to the charge-inverted DNA molecule reverses the sign of the ionic current
      through the pore. Our theory allows for a comprehensive understanding of the
      complex features of the resulting streaming currents. The underlying mechanism is
      an efficient way to detect DNA charge reversal in pressure-driven translocation
      experiments with multivalent cations. 

PMID- 25768785
TI  - Foreshock and aftershocks in simple earthquake models.
AB  - Many models of earthquake faults have been introduced that connect Gutenberg
      Richter (GR) scaling to triggering processes. However, natural earthquake fault
      systems are composed of a variety of different geometries and materials and the
      associated heterogeneity in physical properties can cause a variety of spatial
      and temporal behaviors. This raises the question of how the triggering process
      and the structure interact to produce the observed phenomena. Here we present a
      simple earthquake fault model based on the Olami-Feder-Christensen and Rundle
      Jackson-Brown cellular automata models with long-range interactions that
      incorporates a fixed percentage of stronger sites, or asperity cells, into the
      lattice. These asperity cells are significantly stronger than the surrounding
      lattice sites but eventually rupture when the applied stress reaches their higher
      threshold stress. The introduction of these spatial heterogeneities results in
      temporal clustering in the model that mimics that seen in natural fault systems
      along with GR scaling. In addition, we observe sequences of activity that start
      with a gradually accelerating number of larger events (foreshocks) prior to a
      main shock that is followed by a tail of decreasing activity (aftershocks). This
      work provides further evidence that the spatial and temporal patterns observed in
      natural seismicity are strongly influenced by the underlying physical properties
      and are not solely the result of a simple cascade mechanism. 

PMID- 25768786
TI  - Endogenous crisis waves: stochastic model with synchronized collective behavior.
AB  - We propose a simple framework to understand commonly observed crisis waves in
      macroeconomic agent-based models, which is also relevant to a variety of other
      physical or biological situations where synchronization occurs. We compute
      exactly the phase diagram of the model and the location of the synchronization
      transition in parameter space. Many modifications and extensions can be studied,
      confirming that the synchronization transition is extremely robust against
      various sources of noise or imperfections. 

PMID- 25768787
TI  - Comment on "counterintuitive dispersion violating Kramers-Kronig relations in
      gain slabs".

PMID- 25768788
TI  - Wang et al. Reply.

PMID- 25768789
TI  - Mo2Ga2C: a new ternary nanolaminated carbide.
AB  - We report the discovery of a new hexagonal Mo2Ga2C phase, wherein two Ga layers -
      instead of one - are stacked in a simple hexagonal arrangement in between Mo2C
      layers. It is reasonable to assume this compound is the first of a larger family.

PMID- 25768790
TI  - Research Forum on Changes in Sensory Perception in Middle-Aged Adults: A Summary
      of a Special Session at Hearing Across the Lifespan (HEAL) 2014.
AB  - PURPOSE: The purpose of this article is to introduce the special research forum
      on sensory-processing changes in middle-aged adults. METHOD: This is a brief
      written introduction to the special session, which included five presentations,
      each emphasizing a slightly different aspect of sensory perception. CONCLUSION:
      The effects of aging on sensory processing, including auditory processing and
      speech perception, are not confined to older adults but begin in middle age in
      many cases.

PMID- 25768791
TI  - Establishment of nature reserves in administrative regions of mainland China.
AB  - Nature reserves are widely considered as one available strategy for protecting
      biodiversity, which is threatened by habitat fragmentation, and wildlife
      extinction. The Chinese government has established a goal of protecting 15% of
      its land area by 2015. We quantitated the characteristics and distribution of
      nature reserves in mainland China and evaluated the expansion process for
      national nature reserves. National nature reserves occupy 64.15% of the total
      area of nature reserves. Steppe and meadow ecosystem, ocean and seacoast
      ecosystem, and wild plant nature reserves represent lower percentages,
      particularly in national nature reserves, in which they comprised 0.76%, 0.54%,
      and 0.69%, respectively, of the area. Furthermore, medium and small nature
      reserves compose 92.32% of all nature reserves. The land area under any legal
      protection has reached 14.80%, although only 9.78% is strictly protected.
      However, if 9 super-large national nature reserves, located in Southwest and
      Northwest China were removed, the percentage of strictly protected area decreases
      to 2.66% of the land area of China. The areas contained in nature reserves in
      each province are not proportional to the areas of the provinces, particularly
      for national nature reserves, with higher protection rates in Southwest and
      Northwest China than in other regions. Of the 31 provinces, 22 provinces feature
      strict protection of less than 4% of their areas by national nature reserves;
      these provinces are mainly located in East, Central, South, and North China.
      Moreover, the unevenness indexes of the distribution of nature reserves and
      national nature reserves are 0.39 and 0.58, respectively. The construction of
      nature reserves has entered a steady development stage after a period of rapid
      expansion in mainland China. In recent years, the total area of national nature
      reserves has increased slowly, while the total area of nature reserves has not
      increased, although the number of nature reserves continues increase. 

PMID- 25768792
TI  - Copper-catalyzed selective arylations of benzoxazoles with aryl iodides.
AB  - A copper-catalyzed direct ring-opening double N-arylation of benzoxazoles with
      aryl iodides has been developed. The present system exhibits high selectivity
      despite competition from C-arylation. The selectivity between ring-opening N
      arylation and C-arylation was controlled by the choice of reaction vessel. The
      nitrile bound bis(triphenylphosphine)copper cyanide was identified as the active
      catalytic species for both reactions, and when combined with a nitrile-containing
      solvent, enhanced the reaction efficiency. 

PMID- 25768793
TI  - Load characteristics of a suspended carbon nanotube film heater and the
      fabrication of a fast-response thermochromic display prototype.
AB  - The influence of heating load on the thermal response of a CNT film heater has
      been studied. Two kinds of heat dissipation modes, thermal radiation in a vacuum
      and convection in the atmosphere, are investigated, respectively. It is found
      that the thermal response slows down with the load quantities in the both cases.
      We have further studied the thermal response of a CNT film loaded with
      thermochromic pigment, which is a kind of phase change material. In addition to
      the thermal response slowing down with the load quantity, it is also found that
      the phase change of the thermochromic pigments can also slow down the thermal
      response. With a suspended CNT film heater structure, we have fabricated a
      thermochromic display prototype, which can switch from room temperature to 50 
      degrees C in about 1 s with a brightness contrast of 4.8 under normal indoor
      illumination. A 16 * 16 pixel thermochromic display prototype can dynamically
      display Chinese characters driven by a homemade circuit. 

PMID- 25768794
TI  - Production of anti-LPS IgM by B1a B cells depends on IL-1beta and is protective
      against lung infection with Francisella tularensis LVS.
AB  - The role of IL-1beta and IL-18 during lung infection with the gram-negative
      bacterium Francisella tularensis LVS has not been characterized in detail. Here,
      using a mouse model of pneumonic tularemia, we show that both cytokines are
      protective, but through different mechanisms. Il-18-/- mice quickly succumb to
      the infection and showed higher bacterial burden in organs and lower level of
      IFNgamma in BALF and serum compared to wild type C57BL/6J mice. Administration of
      IFNgamma rescued the survival of Il-18-/- mice, suggesting that their decreased
      resistance to tularemia is due to inability to produce IFNgamma. In contrast,
      mice lacking IL-1 receptor or IL-1beta, but not IL-1alpha, appeared to control
      the infection in its early stages, but eventually succumbed. IFNgamma
      administration had no effect on Il-1r1-/- mice survival. Rather, Il-1r1-/- mice
      were found to have significantly reduced titer of Ft LPS-specific IgM. The anti
      Ft LPS IgM was generated in a IL-1beta-, TLR2-, and ASC-dependent fashion,
      promoted bacteria agglutination and phagocytosis, and was protective in passive
      immunization experiments. B1a B cells produced the anti-Ft LPS IgM and these
      cells were significantly decreased in the spleen and peritoneal cavity of
      infected Il-1b-/- mice, compared to C57BL/6J mice. Collectively, our results show
      that IL-1beta and IL-18 activate non-redundant protective responses against
      tularemia and identify an essential role for IL-1beta in the rapid generation of
      pathogen-specific IgM by B1a B cells. 

PMID- 25768795
TI  - Binge ethanol prior to traumatic brain injury worsens sensorimotor functional
      recovery in rats.
AB  - A significant number of patients suffering from traumatic brain injury (TBI) have
      a high blood alcohol level at the time of injury. Furthermore, drinking alcohol
      in a binge-like pattern is now recognized as a national problem, leading to a
      greater likelihood of being injured. Our objective was to determine the
      consequences of a binge paradigm of alcohol intoxication at the time of TBI on
      long-term functional outcome using a sensitive test of sensorimotor function. We
      trained adult, male, Sprague Dawley rats on the skilled forelimb reaching task
      and then administered a single binge dose of ethanol (2 g/kg, i.p.) or saline for
      three consecutive days (for a total of 3 doses). One hour after the final ethanol
      dose, rats underwent a TBI to the sensorimotor cortex corresponding to the
      preferred reaching forelimb. Animals were then tested for seven weeks on the
      skilled forelimb reaching task to assess the profile of recovery. We found that
      the group given ethanol prior to TBI displayed a slower recovery curve with a
      lower recovery plateau as compared to the control group. Therefore, even a
      relatively short (3 day) episode of binge alcohol exposure can negatively impact
      long-term recovery from a TBI, underscoring this significant public health
      problem.

PMID- 25768796
TI  - Epilation for minor trachomatous trichiasis: four-year results of a randomised
      controlled trial.
AB  - BACKGROUND: Trachomatous trichiasis (TT) needs to be managed to reduce the risk
      of vision loss. The long-term impact of epilation (a common traditional practice
      of repeated plucking of lashes touching the eye) in preventing visual impairment
      and corneal opacity from TT is unknown. We conducted a randomized controlled
      trial of epilation versus surgery for the management of minor TT (fewer than six
      lashes touching the eye) in Ethiopia. Here we report the four-year outcome and
      the effect on vision and corneal opacity. METHODOLOGY/ PRINCIPAL FINDINGS: 1300
      individuals with minor TT were recruited and randomly assigned to quality
      trichiasis surgery or repeated epilation using high quality epilation forceps by
      a trained person with good near vision. Participants were examined six-monthly
      for two-years, and then at four-years after randomisation. At two-years all
      epilation arm participants were offered free surgery. At four-years 1151 (88.5%)
      were re-examined: 572 (88%) and 579 (89%) from epilation and surgery arms,
      respectively. At that time, 21.1% of the surgery arm participants had recurrent
      TT; 189/572 (33%) of the epilation arm had received surgery, while 383 (67%)
      declined surgery and had continued epilating ("epilation-only"). Among the
      epilation-only group, 207 (54.1%) fully controlled their TT, 166 (43.3%) had
      minor TT and 10 (2.6%) had major TT (>5 lashes). There were no differences
      between participants in the epilation-only, epilation-to-surgery and surgery arm
      participants in changes in visual acuity and corneal opacity between baseline and
      four-years. CONCLUSIONS/ SIGNIFICANCE: Most minor TT participants randomised to
      the epilation arm continued epilating and controlled their TT. Change in vision
      and corneal opacity was comparable between surgery and epilation-only
      participants. This suggests that good quality epilation with regular follow-up is
      a reasonable second-line alternative to surgery for minor TT for individuals who
      either decline surgery or do not have immediate access to surgical treatment.

PMID- 25768797
TI  - Adamantane-resistant influenza a viruses in the world (1902-2013): frequency and
      distribution of M2 gene mutations.
AB  - Adamantanes (amantadine and rimantadine) have been used to prevent and treat
      influenza A virus infections for many years; however, resistance to these drugs
      has been widely reported in the world. To investigate the frequency and
      distribution of M2 gene mutations in adamantane-resistant influenza variants
      circulated in the world between 1902 and 2013, 31251 available M2 protein
      sequences from different HA-subtype influenza A viruses (H1-H17) were analyzed
      and adamantane resistance-associated mutations were compared (L26F, V27A, A30T,
      A30V, S31N, G34E, and L38F). We find that 45.2% (n = 14132) of influenza A (H1
      H17) viruses circulating globally were resistant to adamantanes, and the vast
      majority of resistant viruses (95%) bear S31N mutations. Whereas, only about 1%
      have V27A mutations and other mutations (L26F, A30T, G34E, and L38F) were
      extremely rare (their prevalence appeared to be < 0.2%). Our results confirm that
      H1, H3, H5, H7, H9, and H17 subtype influenza A viruses exhibit high-level
      resistance to adamantanes. In contrast, the appearance of adamantane-resistant
      mutants in H2, H4, H6, H10, and H11 subtypes was rare. However, no adamantane
      resistance viruses were identified among other HA subtypes (H8, H12-H16). Our
      findings indicate that the frequency and distribution of adamantane-resistant
      influenza variants varied among different HA subtypes, host species, years of
      isolation, and geographical areas. This comprehensive study raises concerns about
      the increasing prevalence of adamantane-resistant influenza A viruses and
      highlights the importance of monitoring the emergence and worldwide spread of
      adamantane-resistant variants. 

PMID- 25768798
TI  - Effective permeabilities of abandoned oil and gas wells: analysis of data from
      Pennsylvania.
AB  - Abandoned oil and gas (AOG) wells can provide pathways for subsurface fluid
      migration, which can lead to groundwater contamination and gas emissions to the
      atmosphere. Little is known about the millions of AOG wells in the U.S. and
      abroad. Recently, we acquired data on methane emissions from 42 plugged and
      unplugged AOG wells in five different counties across western Pennsylvania. We
      used historical documents to estimate well depths and used these depths with the
      emissions data to estimate the wells' effective permeabilities, which capture the
      combined effects of all leakage pathways within and around the wellbores. We find
      effective permeabilities to range from 10(-6) to 10(2) millidarcies, which are
      within the range of previous estimates. The effective permeability data presented
      here provide perspective on older AOG wells and are valuable when considering the
      leakage potential of AOG wells in a wide range of applications, including
      geologic storage of carbon dioxide, natural gas storage, and oil and gas
      development. 

PMID- 25768799
TI  - The role of China in the global spread of the current cholera pandemic.
AB  - Epidemics and pandemics of cholera, a severe diarrheal disease, have occurred
      since the early 19th century and waves of epidemic disease continue today.
      Cholera epidemics are caused by individual, genetically monomorphic lineages of
      Vibrio cholerae: the ongoing seventh pandemic, which has spread globally since
      1961, is associated with lineage L2 of biotype El Tor. Previous genomic studies
      of the epidemiology of the seventh pandemic identified three successive sub
      lineages within L2, designated waves 1 to 3, which spread globally from the Bay
      of Bengal on multiple occasions. However, these studies did not include samples
      from China, which also experienced multiple epidemics of cholera in recent
      decades. We sequenced the genomes of 71 strains isolated in China between 1961
      and 2010, as well as eight from other sources, and compared them with 181
      published genomes. The results indicated that outbreaks in China between 1960 and
      1990 were associated with wave 1 whereas later outbreaks were associated with
      wave 2. However, the previously defined waves overlapped temporally, and are an
      inadequate representation of the shape of the global genealogy. We therefore
      suggest replacing them by a series of tightly delineated clades. Between 1960 and
      1990 multiple such clades were imported into China, underwent further
      microevolution there and then spread to other countries. China was thus both a
      sink and source during the pandemic spread of V. cholerae, and needs to be
      included in reconstructions of the global patterns of spread of cholera. 

PMID- 25768807
TI  - Real-time patient survey data during routine clinical activities for rapid-cycle
      quality improvement.
AB  - BACKGROUND: Surveying patients is increasingly important for evaluating and
      improving health care delivery, but practical survey strategies during routine
      care activities have not been available. OBJECTIVE: We examined the feasibility
      of conducting routine patient surveys in a primary care clinic using commercially
      available technology (Web-based survey creation, deployment on tablet computers,
      cloud-based management of survey data) to expedite and enhance several steps in
      data collection and management for rapid quality improvement cycles. METHODS: We
      used a Web-based data management tool (survey creation, deployment on tablet
      computers, real-time data accumulation and display of survey results) to conduct
      four patient surveys during routine clinic sessions over a one-month period. Each
      survey consisted of three questions and focused on a specific patient care domain
      (dental care, waiting room experience, care access/continuity, Internet
      connectivity). RESULTS: Of the 727 available patients during clinic survey days,
      316 patients (43.4%) attempted the survey, and 293 (40.3%) completed the survey.
      For the four 3-question surveys, the average time per survey was overall 40.4
      seconds, with a range of 5.4 to 20.3 seconds for individual questions. Yes/No
      questions took less time than multiple choice questions (average 9.6 seconds
      versus 14.0). Average response time showed no clear pattern by order of questions
      or by proctor strategy, but monotonically increased with number of words in the
      question (<20 words, 21-30 words, >30 words)-8.0, 11.8, 16.8, seconds,
      respectively. CONCLUSIONS: This technology-enabled data management system helped
      capture patient opinions, accelerate turnaround of survey data, with minimal
      impact on a busy primary care clinic. This new model of patient survey data
      management is feasible and sustainable in a busy office setting, supports and
      engages clinicians in the quality improvement process, and harmonizes with the
      vision of a learning health care system.

PMID- 25768800
TI  - Individualized homeopathic treatment and fluoxetine for moderate to severe
      depression in peri- and postmenopausal women (HOMDEP-MENOP study): a randomized,
      double-dummy, double-blind, placebo-controlled trial.
AB  - BACKGROUND: Perimenopausal period refers to the interval when women's menstrual
      cycles become irregular and is characterized by an increased risk of depression.
      Use of homeopathy to treat depression is widespread but there is a lack of
      clinical trials about its efficacy in depression in peri- and postmenopausal
      women. The aim of this study was to assess efficacy and safety of individualized
      homeopathic treatment versus placebo and fluoxetine versus placebo in peri- and
      postmenopausal women with moderate to severe depression. METHODS/DESIGN: A
      randomized, placebo-controlled, double-blind, double-dummy, superiority, three
      arm trial with a 6 week follow-up study was conducted. The study was performed in
      a public research hospital in Mexico City in the outpatient service of
      homeopathy. One hundred thirty-three peri- and postmenopausal women diagnosed
      with major depression according to DSM-IV (moderate to severe intensity) were
      included. The outcomes were: change in the mean total score among groups on the
      17-item Hamilton Rating Scale for Depression, Beck Depression Inventory and
      Greene Scale, after 6 weeks of treatment, response and remission rates, and
      safety. Efficacy data were analyzed in the intention-to-treat population (ANOVA
      with Bonferroni post-hoc test). RESULTS: After a 6-week treatment, homeopathic
      group was more effective than placebo by 5 points in Hamilton Scale. Response
      rate was 54.5% and remission rate, 15.9%. There was a significant difference
      among groups in response rate definition only, but not in remission rate.
      Fluoxetine-placebo difference was 3.2 points. No differences were observed among
      groups in the Beck Depression Inventory. Homeopathic group was superior to
      placebo in Greene Climacteric Scale (8.6 points). Fluoxetine was not different
      from placebo in Greene Climacteric Scale. CONCLUSION: Homeopathy and fluoxetine
      are effective and safe antidepressants for climacteric women. Homeopathy and
      fluoxetine were significantly different from placebo in response definition only.
      Homeopathy, but not fluoxetine, improves menopausal symptoms scored by Greene
      Climacteric Scale. TRIAL REGISTRATION: ClinicalTrials.gov NCT01635218. PROTOCOL
      PUBLICATION: https://clinicaltrials.gov/ct2/show/NCT01635218 [corrected].

PMID- 25768808
TI  - A multifactorial injury prevention intervention reduces injury incidence in
      Physical Education Teacher Education students.
AB  - Physical Education Teacher Education (PETE) students are at considerable risk for
      non-contact sports injuries of the lower extremities. Multifactorial injury
      prevention interventions including exercises have been successful in sports
      populations, but no such study has ever been performed in PETE students. This
      study investigated the efficacy of a multifactorial injury prevention
      intervention on injury incidence reduction in PETE students. PETE students in the
      intervention group (n = 154) and in the control group (n = 189) registered sports
      injuries prospectively. The intervention lasted one academic year and consisted
      of an injury awareness programme and preventive strategies, implemented by the
      PETE sports lecturers. Differences in injury incidence between the intervention
      and control group were tested by Poisson regression Wald tests. There was a trend
      towards significantly lower incidence rate (2.18 vs. 2.73; p = 0.061) in the
      intervention group compared with the control group. Students in the intervention
      group had significantly less acute, first-time and extracurricular injuries. The
      largest reduction was observed for injuries during unsupervised practice
      sessions. A multifactorial injury prevention intervention embedded into a regular
      PETE programme is a promising and feasible strategy to prevent injuries in PETE
      students. Further research is needed to investigate whether the results may be
      generalised to other PETE programmes. 

PMID- 25768809
TI  - A two-layer linear piezoelectric micromotor.
AB  - A first bending (B1) mode two-layer piezoelectric ultrasonic linear micromotor
      has been developed for microoptics driving applications. The piezo-vibrator of
      the micromotor was composed of two small Pb(Zr,Ti)O3 (PZT-5) plates, with overall
      dimensions and mass of only 2.0 * 2.0 * 5.0 mm(3) and 0.2 g, respectively. The
      proposed micromotor could operate either in single-phase voltage (standing wave)
      mode or two-phase voltage (traveling wave) mode to drive a slider via friction
      force to provide bidirectional linear motion. A large thrust of up to 0.30 N,
      which corresponds to a high unit volume direct driving force of 15 mN/mm(3), and
      a linear movement velocity of up to 230 mm/s were obtained under an applied
      voltage of 80 Vpp at the B1 mode resonance frequency of 174 kHz. 

PMID- 25768810
TI  - Multipoint joint time and frequency dissemination in delay-stabilized fiber optic
      links.
AB  - This paper presents the system for dissemination of both the RF frequency (e.g.,
      5, 10, or 100 MHz) and time (pulse per second) signals using an actively tapped
      fiber-optic link with electronic stabilization of the propagation delay. In
      principle several nodes for accessing the time/frequency signals may be added
      without the degradation of the dissemination in the main link. We are discussing
      the algorithm of determining the propagation delay from the local end of the link
      to the access node that is required for calibration of the time dissemination.
      Performed analysis shows that the uncertainty of the time calibration at the
      access node may in practice be dominated by the dependence of the propagation
      delay of the receivers on impinging optical powers and is only weakly affected by
      the distance between the local and access modules. The uncertainty is, however,
      still low, being only about two times higher compared with the calibration
      uncertainty of the main link. Experimental results performed on several spooled
      fibers show that the accuracy of described calibration procedures, expressed as a
      difference from the results of direct measurement, is not worse than 35 ps. 

PMID- 25768811
TI  - Optimization of the autocorrelation weighting function for the time-domain
      calculation of spectral centroids.
AB  - Spectral centroid from the backscattered ultrasound provides important
      information about the attenuation properties of soft tissues and Doppler effects
      of blood flows. Because the spectral centroid is originally determined from the
      power spectrum of backscattered ultrasound signals in the frequency domain, it is
      natural to calculate it after converting time-domain signals into spectral domain
      signals, using the fast Fourier transform (FFT). Recent research, however,
      derived the time-domain equations for calculating the spectral centroid using a
      Parseval's theorem, to avoid the calculation of the Fourier transform. The work
      only presented the final result, which showed that the computational time of the
      proposed time-domain method was 4.4 times faster than that of the original FFT
      based method, whereas the average estimation error was negligible. In this paper,
      we present the optimal design of the autocorrelation weighting function, which is
      used for the timedomain spectral centroid estimation process, to reduce the
      computational time significantly. We also carry out a comprehensive analysis of
      the computational complexities of the FFTbased and time-domain methods with
      respect to the length of ultrasound signal segments. The simulation results using
      numerical phantoms show that, with the optimized autocorrelation weighting
      function, we only need approximately 3% of the full set of data points. In
      addition to that, because the proposed optimization technique requires a fixed
      number of data points to calculate the spectral centroid, the execution time is
      constant as the length of the data segment increases, whereas the execution time
      of the conventional FFT-based method is increased. Analysis of the computational
      complexities between the proposed method and the conventional FFT-based method
      presents O(N) and O(Nlog2N), respectively. 

PMID- 25768812
TI  - High-performance planar ultrasonic tool based on d31-mode piezocrystal.
AB  - Ultrasonic scalpels based on the conventional mass-spring configuration of
      piezoelectric transducers are widely used in procedures such as oral, hepatic,
      and pancreatic surgery. However, the weight and self-heating of this
      configuration are weaknesses. To address these, an alternative approach can be
      adopted which utilizes a planar configuration of a cutting blade to which
      piezoelectric drive components are bonded directly. This paper details the design
      and characterization of three such planar scalpels, made of surgical-grade
      stainless steel and silicon. These tools operate in the d31 mode configuration,
      utilizing relaxor-PT single-crystal binary (PMN-PT) and manganese-doped ternary
      (Mn:PIN-PMN-PT) composition piezoelectric materials. The scalpels, with shapes
      resembling a dagger, are able to produce longitudinal displacements >5 MUm when
      driven with 20 V(p-p) at their respective resonant frequencies, 73 and 106 kHz.
      It is observed that both blade and piezoelectric materials significantly affect
      the performance of the planar tool. The mechanical quality factor, Q(M), of PMNPT
      based silicon tool is ~1500 in air compared with ~350 for its stainless steel
      counterpart, and the use of Mn:PIN-PMNPT further increases the Q(M) to ~2400.
      Furthermore, the study on the effect of various tissue-loading conditions suggest
      that skin is the most difficult tissue to penetrate, consequently leading to
      significant reduction in the tool's efficiency and therefore demanding high-Q(M)
      tools.

PMID- 25768813
TI  - A versatile and experimentally validated finite element model to assess the
      accuracy of shear wave elastography in a bounded viscoelastic medium.
AB  - The feasibility of shear wave elastography (SWE) in arteries for cardiovascular
      risk assessment remains to be investigated as the artery's thin wall and
      intricate material properties induce complex shear wave (SW) propagation
      phenomena. To better understand the SW physics in bounded media, we proposed an
      in vitro validated finite element model capable of simulating SW propagation,
      with full flexibility at the level of the tissue's geometry, material properties,
      and acoustic radiation force. This computer model was presented in a relatively
      basic set-up, a homogeneous slab of gelatin-agar material (4.35 mm thick),
      allowing validation of the numerical settings according to actual SWE
      measurements. The resulting tissue velocity waveforms and SW propagation speed
      matched well with the measurement: 4.46 m/s (simulation) versus 4.63 +/- 0.07 m/s
      (experiment). Further, we identified the impact of geometrical and material
      parameters on the SW propagation characteristics. As expected, phantom thickness
      was a determining factor of dispersion. Adding viscoelasticity to the model
      augmented the estimated wave speed to 4.58 m/s, an even better match with the
      experimental determined value. This study demonstrated that finite element
      modeling can be a powerful tool to gain insight into SWE mechanics and will in
      future work be advanced to more clinically relevant settings. 

PMID- 25768814
TI  - Unique pumping-out fracturing mechanism of a polymer-shelled contrast agent: an
      acoustic characterization and optical visualization.
AB  - This work describes the fracturing mechanism of air-filled microbubbles (MBs)
      encapsulated by a cross-linked poly(vinyl alcohol) (PVA) shell. The radial
      oscillation and fracturing events following the ultrasound exposure were
      visualized with an ultrahigh-speed camera, and backscattered timedomain signals
      were acquired with the acoustic setup specific for harmonic detection. No
      evidence of gas emerging from defects in the shell with the arrival of the first
      insonation burst was found. In optical recordings, more than one shell defect was
      noted, and the gas core was drained without any sign of air extrusion when
      several consecutive bursts of 1 MPa amplitude were applied. In acoustic tests,
      the backscattered peak-to-peak voltage gradually reached its maximum and
      exponentially decreased when the PVA-based MB suspension was exposed to
      approximately 20 consecutive bursts arriving at pulse repetition frequencies of
      100 and 500 Hz. Taking into account that the PVA shell is porous and possibly
      contains large air pockets between the cross-linked PVA chains, the
      aforementioned acoustic behavior might be attributed to pumping gas from these
      pockets in combination with gas release from the core through shell defects. We
      refer to this fracturing mechanism as pumping-out behavior, and this behavior
      could have potential use for the local delivery of therapeutic gases, such as
      nitric oxide. 

PMID- 25768815
TI  - Photoacoustic imaging of nanoparticle- containing cells using single-element
      focused transducer: a simulation study.
AB  - A new theoretical approach for photoacoustic (PA) image simulation of an ensemble
      of cells with endocytosed gold nanoparticles is presented. Each cell was
      approximated as a fluid sphere and suspended in a nonabsorbing fluid medium. It
      was assumed that the cellular optical absorption coefficient changed greatly
      because of endocytosis of nanoparticles; however, thermophysical parameters
      remained unchanged because nanoparticles occupied negligible intracellular
      volume. A frequency-domain method was used to obtain a PA signal from a single
      cell and resultant signal detected by a focused single-element transducer was
      evaluated by convolving signals from many cells with the spatial impulse response
      function of the receiver. The proposed model was explored to simulate PA images
      of numerical phantoms. It was observed that features of the phantoms are retained
      precisely in those simulated images. Also, speckles in PA images are
      significantly suppressed because of strong boundary buildup when cells are
      bounded to a region. Nevertheless, speckle visibility increases when cells are
      not bounded to a region. This approach may be developed as a realistic simulation
      tool for PA imaging of tissue medium utilizing its cellular feature. 

PMID- 25768817
TI  - Effect of element directivity on adaptive beamforming applied to high-frame-rate
      ultrasound.
AB  - High-frame-rate ultrasound is a promising technique for measurement and imaging
      of cardiovascular dynamics. In high-frame-rate ultrasonic imaging, unfocused
      ultrasonic beams are used in transmit and multiple focused receiving beams are
      created by parallel beamforming using the delay and sum (DAS) method. However,
      the spatial resolution and contrast are degraded compared with conventional
      beamforming using focused transmit beams. In the present study, the minimum
      variance beamformer was examined for improvement of the spatial resolution in
      high-frame-rate ultrasound. In conventional minimum variance beamforming, the
      spatial covariance matrix of ultrasonic echo signals received by individual
      transducer elements is obtained without considering the directivity of the
      transducer element. By omitting the element directivity, the error in estimation
      of the desired signal (i.e., the echo from the focal point) increases, and as a
      result, the improvement of the spatial resolution is degraded. In the present
      study, the element directivity was taken into account in estimation of the
      spatial covariance matrix used in minimum variance beamforming. The effect of the
      element directivity on adaptive beamforming was evaluated by computer simulation
      and basic experiments using a phantom. In parallel beamforming with the
      conventional DAS beamformer, the lateral spatial resolution, which was evaluated
      from the lateral full width at half maximum of the echo amplitude profile in the
      basic experiment, was 0.50 mm. Using conventional amplitude and phase estimation
      (APES) beamforming, the lateral spatial resolution was improved to 0.37 mm. The
      lateral spatial resolution was further improved to 0.30 mm using the modified
      APES beamforming by considering the element directivity. Image contrast and
      contrast-to-noise ratios, respectively, were -12.3 and 6.5 dB (DAS), -32.8 and 
      11.3 dB (APES), and -7.0 and 3.1 dB (modified APES). 

PMID- 25768816
TI  - Waveform inversion with source encoding for breast sound speed reconstruction in
      ultrasound computed tomography.
AB  - Ultrasound computed tomography (USCT) holds great promise for improving the
      detection and management of breast cancer. Because they are based on the acoustic
      wave equation, waveform inversion-based reconstruction methods can produce images
      that possess improved spatial resolution properties over those produced by ray
      based methods. However, waveform inversion methods are computationally demanding
      and have not been applied widely in USCT breast imaging. In this work, source
      encoding concepts are employed to develop an accelerated USCT reconstruction
      method that circumvents the large computational burden of conventional waveform
      inversion methods. This method, referred to as the waveform inversion with source
      encoding (WISE) method, encodes the measurement data using a random encoding
      vector and determines an estimate of the sound speed distribution by solving a
      stochastic optimization problem by use of a stochastic gradient descent
      algorithm. Both computer simulation and experimental phantom studies are
      conducted to demonstrate the use of the WISE method. The results suggest that the
      WISE method maintains the high spatial resolution of waveform inversion methods
      while significantly reducing the computational burden. 

PMID- 25768818
TI  - Three-mode coupling of symmetric and antisymmetric Lamb waves in plates with
      finite corrugations.
AB  - Coupled-mode equations governing the amplitudes of the higher-order symmetric
      Lamb modes S1 and S2 with the antisymmetric mode A2 in an infinite elastic plate
      with sinusoidal surface corrugation over a finite length are obtained via
      multiple-scales analysis. This phenomenon of threemode coupling is observed when
      the wavenumbers k(s1) and k(s2) of the symmetric modes and k(A2) of the
      antisymmetric mode satisfy the simultaneous resonance conditions k(s1) - k(A2) =
      k(w) and k(A2) - k(s2) = k(w), where k(w) is the wavenumber of the sinusoidal
      corrugation. Near resonance, the coupled amplitude equations are solved exactly
      as an initial-value problem and it is seen that the modes are transmitted through
      the grating without reflection. Complete conversion from the symmetric modes into
      the antisymmetric mode is observed at periodic intervals along the grating when
      the resonance conditions are exactly satisfied. The effect of detuning away from
      resonance also shows propagation without reflection with periodic energy
      exchange. In the latter case, the modes couple without complete conversion. This
      phenomenon of mode conversion is confirmed by the results of an experiment on an
      aluminum plate with a triangular grating excited with the S2 symmetric mode at
      2.7 MHz.

PMID- 25768819
TI  - Point spread functions and deconvolution of ultrasonic images.
AB  - This article investigates the restoration of ultrasonic pulse-echo C-scan images
      by means of deconvolution with a point spread function (PSF). The deconvolution
      concept from linear system theory (LST) is linked to the wave equation
      formulation of the imaging process, and an analytic formula for the PSF of planar
      transducers is derived. For this analytic expression, different numerical and
      analytic approximation schemes for evaluating the PSF are presented. By comparing
      simulated images with measured C-scan images, we demonstrate that the assumptions
      of LST in combination with our formula for the PSF are a good model for the pulse
      echo imaging process. To reconstruct the object from a C-scan image, we compare
      different deconvolution schemes: the Wiener filter, the ForWaRD algorithm, and
      the Richardson-Lucy algorithm. The best results are obtained with the Richardson
      Lucy algorithm with total variation regularization. For distances greater or
      equal twice the near field distance, our experiments show that the numerically
      computed PSF can be replaced with a simple closed analytic term based on a far
      field approximation. 

PMID- 25768820
TI  - Ultrasonic characterization of crack-like defects using scattering matrix
      similarity metrics.
AB  - Crack-like defects form an important type of target defect in nondestructive
      evaluation, and accurately characterizing them remains a challenge, particularly
      for small cracks and inclined cracks. In this paper, scattering matrices are used
      for defect characterization through use of the correlation coefficient and the
      structural similarity (SSIM) index as similarity metrics. A set of reference
      cracks that have different lengths and orientation angles are compared with the
      test defect and the best match is determined in terms of the maximum similarity
      score between the scattering matrices of the test defect and reference cracks.
      Defect characterization using similarity metrics is invariant to scale and shift,
      so calibration of experimental data is not needed. Principal component analysis
      (PCA) is adopted to reduce the effect of measurement noise and recover the
      original shape of scattering matrices from noisy data. The performance of the
      proposed algorithm is studied in both simulation and experiments. The length and
      orientation angle of four different test cracks are measured at two different
      noise levels in the simulation case, and excellent agreement is achieved between
      the measurement results and the actual values. Experimentally, the lengths of
      five subwavelength cracks are measured to within 0.10 mm, and their orientation
      angles are measured to within 5 degrees . 

PMID- 25768821
TI  - Experimental measurement of the frequency shifts of degenerate thickness-shear
      modes in a rotated Y-cut quartz resonator subject to diametrical forces.
AB  - We report the first experimental measurement of the stress-induced frequency
      shifts of degenerate thickness-shear modes in a rotated Y-cut quartz resonator.
      Two distinct but nominally degenerate modes shifted toward higher frequencies at
      different rates and merged into a single mode as diametrical forces were applied
      gradually. The single mode split into the two distinctive modes progressively as
      the diametrical forces were released. The experimental results are in excellent
      agreement with previous theoretical results and may provide an insight into mode
      coupling phenomena as a possible cause of frequency jumps in quartz resonators.

PMID- 25768822
TI  - Composite ferroelectric FBARs that are switchable between the first and second
      harmonics: experimental demonstration.
AB  - Digital switching between the first and second harmonics, in a composite thin
      film bulk acoustic wave resonator (FBAR), is demonstrated experimentally. The
      FBAR consists of two 180-nm-thick paraelectric-phase Ba0.25Sr0.75TiO3 films
      separated by a 50-nm-thick SrRuO3 conducting layer. The resonant frequency of
      this composite resonator (with Pt bottom and Al top electrodes) is switched from
      3.6 GHz to 7.6 GHz, where the polarity of the 5 V dc bias is reversed on one of
      the ferroelectric films. The frequency switching ratio (f2/f1 >= 2) depends on
      the thickness of the electrodes. Some adjustment of f2/f1 is possible by changing
      the applied dc bias. 

PMID- 25768823
TI  - Computing the acoustic radiation force exerted on a sphere using the
      translational addition theorem.
AB  - In this paper, the translational addition theorem for spherical functions is
      employed to calculate the acoustic radiation force produced by an arbitrary
      shaped beam on a sphere arbitrarily suspended in an inviscid fluid. The procedure
      is also based on the partial-wave expansion method, which depends on the beam
      shape and scattering coefficients. Given a set of beam-shape coefficients (BSCs)
      for an acoustic beam relative to a reference frame, the translational addition
      theorem can be used to obtain the BSCs relative to the sphere positioned anywhere
      in the medium. The scattering coefficients are obtained from the acoustic
      boundary conditions across the sphere's surface. The method based on the addition
      theorem is particularly useful to avoid quadrature schemes to obtain the BSCs. We
      use it to compute the acoustic radiation force exerted by a spherically focused
      beam (in the paraxial approximation) on a silicone-oil droplet (compressible
      fluid sphere). The analysis is carried out in the Rayleigh (i.e., the particle
      diameter is much smaller than the wavelength) and Mie (i.e., the particle
      diameter is of the order of the wavelength or larger) scattering regimes. The
      obtained results show that the paraxial focused beam can only trap particles in
      the Rayleigh scattering regime. 

PMID- 25768824
TI  - Time-resolved gigahertz acoustic wave imaging at arbitrary frequencies.
AB  - We describe a way to generate and detect arbitrary frequency components in time
      resolved surface acoustic wave imaging based on optical pumping and probing with
      a periodic light source. The detailed theory of the technique, based on beam
      modulation and Fourier analysis, for a variety of possible experimental
      configurations is presented, followed by experimental data for a glass substrate
      covered with a thin gold film. We show how the acoustic dispersion relation can
      be obtained to arbitrary frequency resolution, not limited by the laser pulse
      repetition rate. 

PMID- 25768825
TI  - Dynamic leakage current compensation revisited.
AB  - The approach of dynamic leakage current compensation (DLCC) for leaky
      ferroelectrics is revisited. Meyer et al. introduced a calculus based on the
      transient currents recorded during a dynamic hysteresis measurement. Here, a
      complementary calculus based on polarization data is presented which eases data
      processing. The effect of the DLCC is exemplified and some practical limitations
      are given beyond what was presented in 2005. 

PMID- 25768826
TI  - Perfectly matched layer stability in 3-D finite-difference time-domain simulation
      of electroacoustic wave propagation in piezoelectric crystals with different
      symmetry class.
AB  - Perfectly matched layer stability in 3-D finite-difference time-domain
      simulations is demonstrated for two piezoelectric crystals: barium sodium niobate
      and bismuth germanate. Stability is achieved by adapting the discretization grid
      to meet a central-difference scheme. Stability is demonstrated by showing that
      the total energy of the piezoelectric system remains constant in the steady
      state.

PMID- 25768827
TI  - Erratum: Multi-frequency intravascular ultrasound (IVUS) imaging.

PMID- 25768828
TI  - Remote transplantation of a third ventricle colloid cyst: case report.
AB  - The authors report the case of a 15-year-old girl with a third ventricle colloid
      cyst. She presented with prolonged headache, nausea, vomiting, and loss of visual
      acuity with bilateral papilledema. Computed tomography and MRI revealed severe
      biventricular hydrocephalus with transependymal periventricular fluid and a
      minimally enhancing cystic mass of the third ventricle. The patient was diagnosed
      with a colloid cyst and obstructive hydrocephalus, and endoscopic resection with
      ablation of the cyst remnant was performed. While attempting to extricate the
      cyst from the patient's head, control of the cyst was lost and the cyst fell into
      the lateral ventricle beyond the surgeon's view. Postoperative imaging showed
      that the cyst had settled in the right occipital horn. After 3 years of follow
      up, imaging suggests growth of the cyst in its new position without necrosis or
      displacement on prone imaging. 

PMID- 25768829
TI  - Local control after stereotactic radiosurgery for brain metastases in patients
      with melanoma with and without BRAF mutation and treatment.
AB  - OBJECT: BRAF inhibitors improve progression-free and overall survival in patients
      with metastatic melanoma. Brain metastases are common, and stereotactic
      radiosurgery (SRS) has been used, resulting in excellent local control. Because
      BRAF inhibitors are associated with intracranial responses, the authors
      hypothesized that BRAF inhibitors would improve local control in patients with
      melanoma who are receiving SRS for brain metastases. METHODS: The authors
      retrospectively identified patients with metastatic melanoma who had been tested
      for BRAF mutation and treated with SRS for brain metastases. Patients with
      previous resection, multiple brain metastases, or multiple courses of SRS were
      eligible. SRS was delivered in a single fraction to a median dose of 2000 cGy.
      Patients with a BRAF mutation were treated with a BRAF inhibitor on the basis of
      physician preference. RESULTS: The authors identified 52 patients who were
      treated in 82 treatment sessions for 185 brain metastases and 13 tumor beds. At a
      median follow-up of 10.5 months, the 1-year local control rate was 69.2%. At 1
      year, the local control rate for brain metastases in patients with BRAF mutation
      with BRAF treatment was 85.0%, and the local control rate for brain metastases in
      those without BRAF treatment was 51.5% (p = 0.0077). The rates of distant brain
      failure, freedom from whole-brain radiation, and overall survival were not
      different on the basis of BRAF mutation status or inhibitor therapy. The number
      of new intratumoral hemorrhages after SRS was increased significantly in patients
      with BRAF treatment. CONCLUSIONS: Treatment with BRAF inhibitors was associated
      with improved local control after SRS in patients with melanoma and brain
      metastases. An increased number of intratumoral hemorrhages was associated with
      BRAF inhibitor therapy.

PMID- 25768830
TI  - Complications following cranioplasty: incidence and predictors in 348 cases.
AB  - OBJECT: The factors that contribute to periprocedural complications following
      cranioplasty, including patient-specific and surgery-specific factors, need to be
      thoroughly assessed. The aim of this study was to evaluate risk factors that
      predispose patients to an increased risk of cranioplasty complications and death.
      METHODS: The authors conducted a retrospective review of all patients at their
      institution who underwent cranioplasty following craniectomy for stroke,
      subarachnoid hemorrhage, epidural hematoma, subdural hematoma, and trauma between
      January 2000 and December 2011. The following predictors were tested: age, sex,
      race, diabetic status, hypertensive status, tobacco use, reason for craniectomy,
      urgency status of the craniectomy, graft material, and location of cranioplasty.
      The cranioplasty complications included reoperation for hematoma, hydrocephalus
      postcranioplasty, postcranioplasty seizures, and cranioplasty graft infection. A
      multivariate logistic regression analysis was performed. Confidence intervals
      were calculated as the 95% CI. RESULTS: Three hundred forty-eight patients were
      included in the study. The overall complication rate was 31.32% (109 of 348). The
      mortality rate was 3.16%. Predictors of overall complications in multivariate
      analysis were hypertension (OR 1.92, CI 1.22-3.02), increasing age (OR 1.02, CI
      1.00-1.04), and hemorrhagic stroke (OR 3.84, CI 1.93-7.63). Predictors of
      mortality in multivariate analysis were diabetes mellitus (OR 7.56, CI 1.56
      36.58), seizures (OR 7.25, CI 1.238-42.79), bifrontal cranioplasty (OR 5.40, CI
      1.20-24.27), and repeated surgery for hematoma evacuation (OR 13.00, CI 1.51
      112.02). Multivariate analysis was also applied to identify the variables that
      affect the development of seizures, the need for reoperation for hematoma
      evacuation, the development of hydrocephalus, and the development of infections.
      CONCLUSIONS: The authors' goal was to provide the neurosurgeon with predictors of
      morbidity and mortality that could be incorporated in the clinical decision
      making algorithm. Control of a patient's risk factors and early recognition of
      complications may help practitioners avoid the exhaustive list of complications.

PMID- 25768831
TI  - Antimicrobial-impregnated and -coated shunt catheters for prevention of
      infections in patients with hydrocephalus: a systematic review and meta-analysis.
AB  - OBJECT The aim of this study was to evaluate the effectiveness of antimicrobial
      impregnated and -coated shunt catheters (antimicrobial catheters) in reducing the
      risk of infection in patients undergoing CSF shunting or ventricular drainage.
      METHODS The PubMed and Scopus databases were searched. Catheter implantation was
      classified as either shunting (mainly ventriculoperitoneal shunting) or
      ventricular drainage (mainly external [EVD]). Studies evaluating
      antibioticimpregnated catheters (AICs), silver-coated catheters (SCCs), and
      hydrogel-coated catheters (HCCs) were included. A random effects model meta
      analysis was performed. RESULTS Thirty-six studies (7 randomized and 29
      nonrandomized, 16,796 procedures) were included. The majority of data derive from
      studies on the effectiveness of AICs, followed by studies on the effectiveness of
      SCCs. Statistical heterogeneity was observed in several analyses. Antimicrobial
      shunt catheters (AICs, SCCs) were associated with lower risk for CSF catheter
      associated infections than conventional catheters (CCs) (RR 0.44, 95% CI 0.35
      0.56). Fewer infections developed in the patients treated with antimicrobial
      catheters regardless of randomization, number of participating centers, funding,
      shunting or ventricular drainage, definition of infections, de novo implantation,
      and rate of infections in the study. There was no difference regarding gram
      positive bacteria, all staphylococci, coagulase-negative streptococci, and
      Staphylococcus aureus, when analyzed separately. On the contrary, the risk for
      methicillin-resistant S. aureus (MRSA, RR 2.64, 95% CI 1.26-5.51),
      nonstaphylococcal (RR 1.75, 95% CI 1.22-2.52), and gram-negative bacterial (RR
      2.13, 95% CI 1.33-3.43) infections increased with antimicrobial shunt catheters.
      CONCLUSIONS Based on data mainly from nonrandomized studies, AICs and SCCs reduce
      the risk for infection in patients undergoing CSF shunting. Future studies should
      evaluate the higher risk for MRSA and gram-negative infections. Additional trials
      are needed to investigate the comparative effectiveness of the different types of
      antimicrobial catheters.

PMID- 25768832
TI  - Fetal-type posterior cerebral artery: the pitfall of parent artery occlusion for
      ruptured P2 segment and distal aneurysms.
AB  - OBJECT: P2 segment and distal aneurysms are rare lesions of the cerebrovascular
      system. The efficacy and safety of endovascular occlusion for these types of
      aneurysms remain controversial. The aim of this study was to reveal risk factors
      for endovascular parent artery occlusion of ruptured P2 segment and distal
      aneurysms. METHODS: Between March 2010 and November 2012, 812 patients with a
      ruptured intracranial aneurysm were admitted to the authors' hospital. Among
      them, 11 patients presented with P2 segment and distal posterior cerebral artery
      (PCA) aneurysms. These patients were subjected to endovascular treatment.
      Periprocedural data and clinical and angiographic records were studied
      retrospectively. RESULTS: Of the patients with a ruptured PCA aneurysm, 2 of them
      underwent selective aneurismal coiling, and the remaining patients were treated
      with simultaneous occlusion of the parent artery. Patients with an adult-type PCA
      (n = 6), treated with either selective coiling or simultaneous parent artery
      occlusion, had no serious neurological deficits on follow-up. Four patients with
      a fetal-type PCA that was also occluded intraoperatively exhibited newly
      developed permanent paralysis and hemianopsia. However, 1 patient with a fetal
      type PCA aneurysm that was selectively coiled recovered without complications. No
      recanalization was observed in any of the treated aneurysms. CONCLUSIONS:
      Endovascular occlusion of an aneurysm and its parent artery is a safe and
      effective method for managing adult-type P2 segment and distal aneurysms.
      However, the authors' clinical data suggest that this method is of high risk for
      patients with fetal-type PCA aneurysms.

PMID- 25768833
TI  - Survival impact of time to initiation of chemoradiotherapy after resection of
      newly diagnosed glioblastoma.
AB  - OBJECT There are few and conflicting reports on the effects of delayed initiation
      of chemoradiotherapy on the survival of patients with glioblastoma. The standard
      of care for newly diagnosed glioblastoma is concurrent radiotherapy and
      temozolomide chemotherapy after maximal safe resection; however, the optimal
      timing of such therapy is poorly defined. Given the lack of consensus in the
      literature, the authors performed a retrospective analysis of The Cancer Genome
      Atlas (TCGA) database to investigate the effect of time from surgery to
      initiation of therapy on survival in newly diagnosed glioblastoma. METHODS
      Patients with primary glioblastoma diagnosed since 2005 and treated according to
      the standard of care were identified from TCGA database. Kaplan-Meier and
      multivariate Cox regression analyses were used to compare overall survival (OS)
      and progression-free survival (PFS) between groups stratified by postoperative
      delay to initiation of radiation treatment. RESULTS There were 218 patients with
      newly diagnosed glioblastoma with known time to initiation of radiotherapy
      identified in the database. The median duration until therapy was 27 days. Delay
      to radiotherapy longer than the median was not associated with worse PFS (HR =
      0.918, p = 0.680) or OS (HR = 1.135, p = 0.595) in multivariate analysis when
      controlling for age, sex, KPS score, and adjuvant chemotherapy. Patients in the
      highest and lowest quartiles for delay to therapy (<= 20 days vs >= 36 days) did
      not statistically differ in PFS (p = 0.667) or OS (p = 0.124). The small subset
      of patients with particularly long delays (> 42 days) demonstrated worse OS (HR =
      1.835, p = 0.019), but not PFS (p = 0.74). CONCLUSIONS Modest delay in initiation
      of postoperative chemotherapy and radiation does not appear to be associated with
      worse PFS or OS in patients with newly diagnosed glioblastoma, while significant
      delay longer than 6 weeks may be associated with worse OS. 

PMID- 25768834
TI  - Dendritic cell type-specific HIV-1 activation in effector T cells: implications
      for latent HIV-1 reservoir establishment.
AB  - BACKGROUND: Latent HIV type I (HIV-1) infections can frequently occur in short
      lived proliferating effector T lymphocytes. These latently infected cells could
      revert into resting T lymphocytes and thereby contribute to the establishment of
      the long-lived viral reservoir. Monocyte-derived dendritic cells can revert
      latency in effector T cells in vitro. METHODS: Here we investigated the latency
      activation properties of tissue-specific immune cells, including a large panel of
      dendritic cell subsets, to explore in which body compartments effector T cells
      are most likely to maintain latent HIV-1 provirus and thus potentially contribute
      to the long-lived reservoir. RESULTS: Our results demonstrate that blood or
      genital tract dendritic cells do not activate latent provirus in effector T
      cells, whereas gut or lymphoid dendritic cells induce virus production from
      latently infected effector T cells in our in-vitro model for latency. Toll-like
      receptor 3-induced interferon production by myeloid dendritic cells abolished the
      dendritic cells' ability to induce viral gene expression. CONCLUSIONS: In this
      study, we show that HIV-1 provirus residing in effector T cells is activated from
      latency by tissue-specific dendritic cell subsets and other immune cells with
      remarkably different efficiencies.Our new assay system points to an important,
      neglected aspect of HIV-1 research: the ability of other immune cells, especially
      dendritic cells, to differentially affect latency establishment as well as virus
      reactivation.

PMID- 25768835
TI  - Time above 1500 copies: a viral load measure for assessing transmission risk of
      HIV-positive patients in care.
AB  - OBJECTIVE: We examined HIV transmission potential of patients in care by
      analyzing the amount of person-time spent above a viral load threshold that
      increases risk for transmission. DESIGN: Observational cohort and supplemental
      data. METHODS: The cohort included HIV patients who received care at six HIV
      clinics in the United States, from 1 April 2009 to 31 March 2013, and had two or
      more viral load tests during this interval. Person-time (in days) above a viral
      load of 1500 copies/ml out of the total observation time was determined by
      inspecting consecutive pairs of viral load results and the time intervals between
      those pairs. The person-time rate ratios comparing demographic and clinical
      subgroups were estimated with Poisson regression. RESULTS: The cohort included 14
      532 patients observed for a median of 1073 days with a median of nine viral load
      records. Ninety percent of the patients had been prescribed antiretroviral
      therapy. On average, viral load exceeded 1500 copies/ml during 23% of the
      patients' observation time (average of 84 days per year, per patient). Percentage
      of person-time above the threshold was higher among patients who had more than a
      fourth of their viral load pairs exceeding a 6-month interval (34% of observation
      time), patients not on antiretroviral therapy (58% of time), new/re-engaging
      patients (34% of time), patients 16-39 years of age (32% of time), and patients
      of black race (26% of time). CONCLUSION: HIV patients in care spent an average of
      nearly a quarter of their time with viral loads above 1500 copies/ml, higher
      among some subgroups, placing them at risk for potentially transmitting HIV to
      others.

PMID- 25768836
TI  - Targeting the thyroid-stimulating hormone receptor with small molecule ligands
      and antibodies.
AB  - INTRODUCTION: The thyroid-stimulating hormone receptor (TSHR) is the essential
      molecule for thyroid growth and thyroid hormone production. Since it is also a
      key autoantigen in Graves' disease and is involved in thyroid cancer
      pathophysiology, the targeting of the TSHR offers a logical model for disease
      control. AREAS COVERED: We review the structure and function of the TSHR and the
      progress in both small molecule ligands and TSHR antibodies for their therapeutic
      potential. EXPERT OPINION: Stabilization of a preferential conformation for the
      TSHR by allosteric ligands and TSHR antibodies with selective modulation of the
      signaling pathways is now possible. These tools may be the next generation of
      therapeutics for controlling the pathophysiological consequences mediated by the
      effects of the TSHR in the thyroid and other extrathyroidal tissues.

PMID- 25768837
TI  - Inducible and reversible lentiviral and Recombination Mediated Cassette Exchange
      (RMCE) systems for controlling gene expression.
AB  - Manipulation of gene expression to invoke loss of function (LoF) or gain of
      function (GoF) phenotypes is important for interrogating complex biological
      questions both in vitro and in vivo. Doxycycline (Dox)-inducible gene expression
      systems are commonly used although success is often limited by high background
      and insufficient sensitivity to Dox. Here we develop broadly applicable platforms
      for reliable, tightly controlled and reversible Dox-inducible systems for
      lentiviral mediated generation of cell lines or FLP Recombination-Mediated
      Cassette Exchange (RMCE) into the Collagen 1a1 (Col1a1) locus (FLP-In Col1a1) in
      mouse embryonic stem cells. We significantly improve the flexibility, usefulness
      and robustness of the Dox-inducible system by using Tetracycline (Tet) activator
      (Tet-On) variants which are more sensitive to Dox, have no background activity
      and are expressed from single Gateway-compatible constructs. We demonstrate the
      usefulness of these platforms in ectopic gene expression or gene knockdown in
      multiple cell lines, primary neurons and in FLP-In Col1a1 mouse embryonic stem
      cells. We also improve the flexibility of RMCE Dox-inducible systems by
      generating constructs that allow for tissue or cell type-specific Dox-inducible
      expression and generate a shRNA selection algorithm that can effectively predict
      potent shRNA sequences able to knockdown gene expression from single integrant
      constructs. These platforms provide flexible, reliable and broadly applicable
      inducible expression systems for studying gene function. 

PMID- 25768838
TI  - Metabolomic profiling of urine samples from mice exposed to protons reveals
      radiation quality and dose specific differences.
AB  - As space travel is expanding to include private tourism and travel beyond low
      Earth orbit, so is the risk of exposure to space radiation. Galactic cosmic rays
      and solar particle events have the potential to expose space travelers to
      significant doses of radiation that can lead to increased cancer risk and other
      adverse health consequences. Metabolomics has the potential to assess an
      individual's risk by exploring the metabolic perturbations in a biofluid or
      tissue. In this study, C57BL/6 mice were exposed to 0.5 and 2 Gy of 1 GeV/nucleon
      of protons and the levels of metabolites were evaluated in urine at 4 h after
      radiation exposure through liquid chromatography coupled to time-of-flight mass
      spectrometry. Significant differences were identified in metabolites that map to
      the tricarboxylic acid (TCA) cycle and fatty acid metabolism, suggesting that
      energy metabolism is severely impacted after exposure to protons. Additionally,
      various pathways of amino acid metabolism (tryptophan, tyrosine, arginine and
      proline and phenylalanine) were affected with potential implications for DNA
      damage repair and cognitive impairment. Finally, presence of products of purine
      and pyrimidine metabolism points to direct DNA damage or increased apoptosis.
      Comparison of these metabolomic data to previously published data from our
      laboratory with gamma radiation strongly suggests a more pronounced effect on
      metabolism with protons. This is the first metabolomics study with space
      radiation in an easily accessible biofluid such as urine that further
      investigates and exemplifies the biological differences at early time points
      after exposure to different radiation qualities. 

PMID- 25768839
TI  - A Commentary on: "A History of the United States Department of Energy (DOE) Low
      Dose Radiation Research Program: 1998-2008".
AB  - This commentary provides a very brief overview of the book "A History of the
      United States Department of Energy (DOE) Low Dose Radiation Research Program:
      1998-2008" ( http://lowdose.energy.gov ). The book summarizes and evaluates the
      research progress, publications and impact of the U.S. Department of Energy Low
      Dose Radiation Research Program over its first 10 years. The purpose of this book
      was to summarize the impact of the program's research on the current thinking and
      low-dose paradigms associated with the radiation biology field and to help
      stimulate research on the potential adverse and/or protective health effects of
      low doses of ionizing radiation. In addition, this book provides a summary of the
      data generated in the low dose program and a scientific background for anyone
      interested in conducting future research on the effects of low-dose or low-dose
      rate radiation exposure. This book's exhaustive list of publications coupled with
      discussions of major observations should provide a significant resource for
      future research in the low-dose and dose-rate region. However, because of space
      limitations, only a limited number of critical references are mentioned. Finally,
      this history book provides a list of major advancements that were accomplished by
      the program in the field of radiation biology, and these bulleted highlights can
      be found in last part of chapters 4-10. 

PMID- 25768840
TI  - Custom Cast Post Treatment on an Implant Platform in 2 Patients.

PMID- 25768841
TI  - Wolbachia-based population control strategy targeting Culex quinquefasciatus
      mosquitoes proves efficient under semi-field conditions.
AB  - In mosquitoes, the maternally inherited bacterial Wolbachia induce a form of
      embryonic lethality called cytoplasmic incompatibility (CI). This property can be
      used to reduce the density of mosquito field populations through inundative
      releases of incompatible males in order to sterilize females (Incompatible Insect
      Technique, or IIT, strategy). We have previously constructed the LR[wPip(Is)]
      line representing a good candidate for controlling field populations of the Culex
      quinquefasciatus mosquito in the islands of the south-western Indian Ocean. The
      main purpose of the present study was to fill the gap between laboratory
      experiments and field implementation, i.e. assessing mating competitiveness of
      these incompatible males under semi-field conditions. In a first set of
      experiments, we analyzed crossing relationships between LR[wPip(Is)] males and La
      Reunion field females collected as larvae in 19 distinct localities throughout
      the island. This investigation revealed total embryonic mortality, confirming the
      strong sterilizing capacity of LR[wPip(Is)] males. Subsequently, mating
      competitiveness of LR[wPip(Is)] males was assessed under semi-field conditions in
      the presence of field males and females from La Reunion. Confrontations were
      carried out in April and December using different ratios of LR[wPip(Is)] to field
      males. The results indicated that the LR[wPip(Is)] males successfully compete
      with field males in mating with field females, displaying even higher
      competitiveness than field males in April. Our results support the implementation
      of small-scale field tests in order to assess the feasibility of IIT against Cx.
      quinquefasciatus in the islands of southwestern Indian Ocean where this mosquito
      species is a proven competent vector for human pathogens. 

PMID- 25768842
TI  - Neurocognitive and functional correlates of mobile phone use in middle-aged and
      older patients with schizophrenia.
AB  - OBJECTIVES: Our objective was to examine the association of mobile phone use and
      ownership with psychopathology, cognitive functioning, and functional outcome in
      196 outpatients aged 40 years and older who were diagnosed with schizophrenia.
      METHOD: Participants reported their past and current mobile phone use on a
      standardized self-report scale and they were administered tests of global
      cognition, functional capacity, and informant-rated functional outcome. RESULTS:
      The great majority of subjects had used a mobile phone (78%) but few currently
      owned one (27%). After adjusting for age (mean age 51), any past mobile phone use
      was associated with less severe negative symptoms, and higher global cognitive
      performance, functional capacity, and functional outcome. A total of 60% of
      participants reported being comfortable with mobile phones, but comfort was not
      associated with any cognitive or functional outcomes. CONCLUSION: Most of the
      older patients with schizophrenia have used mobile phones and lifetime mobile
      phone use is a positive indicator of cognitive and functional status.

PMID- 25768843
TI  - Specimen extraction after laparoscopic sleeve gastrectomy.

PMID- 25768845
TI  - Mood and Anxiety Disorders in Chronic Fatigue Syndrome, Fibromyalgia, and
      Irritable Bowel Syndrome: Results From the LifeLines Cohort Study.
AB  - OBJECTIVE: Functional somatic syndromes (FSSs) have often been linked to
      psychopathology. The aim of the current study was to compare prevalence rates of
      psychiatric disorders among individuals with chronic fatigue syndrome (CFS),
      fibromyalgia (FM), and irritable bowel syndrome (IBS). METHODS: This study was
      conducted in 94,516 participants (mean [standard deviation] age = 44.6 [12.5]
      years, 58.7% women) of the general-population cohort LifeLines. FSSs were
      assessed by self-reports. Mood disorders (i.e., major depressive disorder and
      dysthymia) and anxiety disorders (i.e., generalized anxiety disorder, social
      phobia, panic disorder with/without agoraphobia, and agoraphobia) were assessed
      by means of the Mini International Neuropsychiatric Interview. Risks on
      psychiatric disorders were compared for individuals with CFS, FM, and IBS by
      using logistic regression analyses adjusted for age and sex. RESULTS: Prevalence
      rates of CFS, FM, and IBS were 1.3%, 3.0%, and 9.7%, respectively. Individuals
      with CFS, FM, and IBS had significantly more mood (odds ratios [ORs] = 1.72-5.42)
      and anxiety disorders (ORs = 1.52-3.96) than did individuals without FSSs, but
      prevalence rates were low (1.6%-28.6%). Individuals with CFS more often had mood
      (ORs = 2.00-4.08) and anxiety disorders (ORs = 1.63-2.32) than did individuals
      with FM and IBS. Major depressive disorder was more common in FM than in IBS (OR
      = 1.58, 95% confidence interval = 1.24-2.01), whereas these groups did not differ
      on dysthymia or anxiety disorders. CONCLUSIONS: Mood and anxiety disorders are
      more prevalent in individuals with FSSs, and particularly CFS, than in
      individuals without FSSs. However, most individuals with FSSs do not have mood or
      anxiety disorders.

PMID- 25768844
TI  - Prospective evaluation of associations between prenatal cortisol and adulthood
      coronary heart disease risk: the New England family study.
AB  - OBJECTIVE: Increasing evidence suggests that early life factors may influence
      coronary heart disease (CHD) risk; however, little is known about the
      contributions of prenatal cortisol. Objectives were to prospectively assess the
      associations of maternal cortisol levels during pregnancy with offspring's 10
      year CHD risk during middle age. METHODS: Participants were 262 mother-offspring
      dyads from the New England Family Study. Maternal free cortisol was assessed in
      third-trimester maternal serum samples. Ten-year CHD risk was calculated in
      offspring at a mean age of 42 years, using the validated Framingham risk
      algorithm incorporating diabetes, systolic and diastolic blood pressure, total
      and high-density lipoprotein cholesterol, smoking, age, and sex. RESULTS: In
      multivariable-adjusted linear regression analyses adjusted for age and
      race/ethnicity, high versus low maternal cortisol tertile was associated with
      36.7% (95% confidence interval [CI] = 8.4% to 72.5%) greater mean 10-year CHD
      risk score in women. There was no association in men (-2.8%, 95% CI = -23.8% to
      24.0%). Further adjustment for in utero socioeconomic position showed 26.1% (95%
      CI = -0.5% to 59.9%) greater CHD risk in women. Adjustment for maternal age and
      size for gestational age had little effect on findings. CONCLUSIONS: Maternal
      prenatal cortisol levels were positively associated with 10-year CHD risk among
      female, and not male, offspring. Adjusting for socioeconomic position during
      pregnancy reduced effect size in women, suggesting that it may be a common prior
      factor in both maternal cortisol and CHD risk. These findings provide evidence
      that targeting mothers who have elevated prenatal cortisol levels, including
      elevated cortisol in the setting of low socioeconomic position, may potentially
      reduce long-term CHD risk in their offspring.

PMID- 25768846
TI  - N-hydroxycinnamide derivatives of osthole ameliorate hyperglycemia through
      activation of AMPK and p38 MAPK.
AB  - Our previous studies found that osthole markedly reduced blood glucose levels in
      both db/db and ob/ob mice. To improve the antidiabetic activity of osthole, a
      series of N-hydroxycinnamide derivatives of osthole were synthesized, and their
      hypoglycemia activities were examined in vitro and in vivo. Both N
      hydroxycinnamide derivatives of osthole, OHC-4p and OHC-2m, had the greatest
      potential for activating AMPK and increasing glucose uptake by L6 skeletal muscle
      cells. In addition, OHC-4p and OHC-2m time- and dose-dependently increased
      phosphorylation levels of AMPK and p38 MAPK. The AMPK inhibitor, compound C, and
      the p38 MAPK inhibitor, SB203580, significantly reversed activation of AMPK and
      p38 MAPK, respectively, in OHC-4p- and OHC-2m-treated cells. Compound C and
      SB203580 also inhibited glucose uptake induced by OHC-4p and OHC-2m. Next, we
      found that OHC-4p and OHC-2m significantly increased glucose transporter 4
      (GLUT4) translocation to plasma membranes and counteracted hyperglycemia in mice
      with streptozotocin-induced diabetes. These results suggest that activation of
      AMPK and p38 MAPK by OHC-4p and OHC-2m is associated with increased glucose
      uptake and GLUT4 translocation and subsequently led to amelioration of
      hyperglycemia. Therefore, OHC-4p and OHC-2m might have potential as antidiabetic
      agents for treating type 2 diabetes. Our previous studies found that osthole
      markedly reduced blood glucose levels in both db/db and ob/ob mice. To improve
      the antidiabetic activity of osthole, a series of N-hydroxycinnamide derivatives
      of osthole were synthesized, and their hypoglycemia activities were examined in
      vitro and in vivo. Both N-hydroxycinnamide derivatives of osthole, OHC-4p and OHC
      2m, had the greatest potential for activating AMPK and increasing glucose uptake
      by L6 skeletal muscle cells. In addition, OHC-4p and OHC-2m time- and dose
      dependently increased phosphorylation levels of AMPK and p38 MAPK. The AMPK
      inhibitor, compound C, and the p38 MAPK inhibitor, SB203580, significantly
      reversed activation of AMPK and p38 MAPK, respectively, in OHC-4p- and OHC-2m
      treated cells. Compound C and SB203580 also inhibited glucose uptake induced by
      OHC-4p and OHC-2m. Next, we found that OHC-4p and OHC-2m significantly increased
      glucose transporter 4 (GLUT4) translocation to plasma membranes and counteracted
      hyperglycemia in mice with streptozotocin-induced diabetes. These results suggest
      that activation of AMPK and p38 MAPK by OHC-4p and OHC-2m is associated with
      increased glucose uptake and GLUT4 translocation and subsequently led to
      amelioration of hyperglycemia. Therefore, OHC-4p and OHC-2m might have potential
      as antidiabetic agents for treating type 2 diabetes. 

PMID- 25768848
TI  - American marten respond to seismic lines in northern Canada at two spatial
      scales.
AB  - Development of hydrocarbon resources across northwest Canada has spurred economic
      prosperity and generated concerns over impacts to biodiversity. To balance these
      interests, numerous jurisdictions have adopted management thresholds that allow
      for limited energy development but minimize undesirable impacts to wildlife. Used
      for exploration, seismic lines are the most abundant linear feature in the boreal
      forest and exist at a variety of widths and recovery states. We used American
      marten (Martes americana) as a model species to measure how line attributes
      influence species' response to seismic lines, and asked whether responses to
      individual lines trigger population impacts. Marten response to seismic lines was
      strongly influenced by line width and recovery state. Compared to forest
      interiors, marten used open seismic lines >= 3 m wide less often, but used open
      lines <= 2 m wide and partially recovered lines >= 6 m wide similarly. Marten
      response to individual line types appeared to trigger population impacts. The
      probability of occurrence at the home range scale declined with increasing
      seismic line density, and the inclusion of behavioral response to line density
      calculations improved model fit. In our top performing model, we excluded seismic
      lines <= 2 m from our calculation of line density, and the probability of
      occurrence declined > 80% between home ranges with the lowest and highest line
      densities. Models that excluded seismic lines did not strongly explain
      occurrence. We show how wildlife-derived metrics can inform regulatory guidelines
      to increase the likelihood those guidelines meet intended management objectives.
      With respect to marten, not all seismic lines constitute disturbances, but
      avoidance of certain line types scales to population impacts. This approach
      provides the ecological context required to understand cause and effect
      relationships among socio-economic and ecological conservation goals. 

PMID- 25768847
TI  - High-fat diet-induced adiposity, adipose inflammation, hepatic steatosis and
      hyperinsulinemia in outbred CD-1 mice.
AB  - High-fat diet (HFD) has been applied to a variety of inbred mouse strains to
      induce obesity and obesity related metabolic complications. In this study, we
      determined HFD induced development of metabolic disorders on outbred female CD-1
      mice in a time dependent manner. Compared to mice on regular chow, HFD-fed CD-1
      mice gradually gained more fat mass and consequently exhibited accelerated body
      weight gain, which was associated with adipocyte hypertrophy and up-regulated
      expression of adipose inflammatory chemokines and cytokines such as Mcp-1 and Tnf
      alpha. Increased fat accumulation in white adipose tissue subsequently led to
      ectopic fat deposition in brown adipose tissue, giving rise to whitening of brown
      adipose tissue without altering plasma level of triglyceride. Ectopic fat
      deposition was also observed in the liver, which was associated with elevated
      expression of key genes involved in hepatic lipid sequestration, including Ppar
      gamma2, Cd36 and Mgat1. Notably, adipose chronic inflammation and ectopic lipid
      deposition in the liver and brown fat were accompanied by glucose intolerance and
      insulin resistance, which was correlated with hyperinsulinemia and pancreatic
      islet hypertrophy. Collectively, these results demonstrate sequentially the
      events that HFD induces physiological changes leading to metabolic disorders in
      an outbred mouse model more closely resembling heterogeneity of the human
      population. 

PMID- 25768851
TI  - An undercovered health threat in Turkey: transdermal methanol intoxication.
AB  - Methanol is a clear, colorless solvent used in antifreeze solutions, varnishes,
      cologne, copying machine fluids, perfume, spirit, paint, and fuel. Even small
      amounts of ingested methanol can cause acute permanent neurological dysfunction
      and irreversible blindness. Although there are many reports of methanol poisoning
      due to suicidal or accidental ingestion, reports of transdermal absorption are
      rare. We present a 68-year-old man with transdermal methanol intoxication applied
      to our hospital's emergency department with weakness, loss of vision, and altered
      state of consciousness. 

PMID- 25768850
TI  - Effect of midazolam on memory during fiberoptic gastroscopy under conscious
      sedation.
AB  - OBJECTIVE: As the fiberoptic gastroscopy using midazolam is being in widespread
      use, the exact nature of midazolam on memory should be clarified. We intended to
      examine whether midazolam causes selective anterograde amnesia and what impact it
      has on other aspects of memory and general cognitive function. METHODS: We
      recruited healthy subjects undergoing fiberoptic gastroscopy under conscious
      sedation. At baseline, history taking for retrograde amnesia and the Korean
      version of the Montreal Cognitive Assessment were performed. A man's name and
      address were given immediately after intravenous midazolam administration. After
      gastroscopy, the subjects were asked to recall those items. By the time they had
      fully recovered consciousness, the same test was repeated along with the Korean
      version of the Montreal Cognitive Assessment and a test for retrograde amnesia.
      RESULTS: A total of 30 subjects were enrolled in this study. Subjects with high
      dose midazolam showed lower scores in the immediate and delayed recall of "a
      man's name and address" compared with those with low-dose midazolam. The
      midazolam dose was inversely correlated with the delayed recall scores of "a
      man's name and address." On full recovery of consciousness, the subjects did not
      exhibit any of anterograde or retrograde amnesia. CONCLUSIONS: These findings
      suggest that midazolam causes transient selective anterograde amnesia in a dose
      dependent manner.

PMID- 25768849
TI  - A long-term study of istradefylline safety and efficacy in patients with
      Parkinson disease.
AB  - OBJECTIVES: Istradefylline is a selective adenosine A2A receptor antagonist. We
      evaluated the safety and efficacy of istradefylline administered once daily for
      52 weeks in Parkinson disease (PD) patients experiencing wearing-off symptoms on
      levodopa therapy. METHODS: This was a phase 3, multicenter, open-label, long-term
      study in PD patients experiencing wearing-off who had previously completed a
      double-blind placebo-controlled clinical study of istradefylline in Japan.
      Istradefylline was administered for 52 weeks at a starting dosage of 20 mg/d,
      with or without dosage adjustment up to 40 mg/d. Safety was assessed using the
      incidence of treatment-emergent adverse events, and efficacy was assessed as the
      change in the daily off time. RESULTS: A total of 308 patients were included in
      this study. The most frequently reported treatment-emergent adverse events were
      nasopharyngitis (24.4%) and dyskinesia (21.4%). The mean change in the daily off
      time from day 1 was -0.65 hour in week 2, fluctuating between -0.71 and -0.04
      hour until week 52 in patients who had previously taken placebo in the preceding
      double-blind study. The off time reduction from baseline of the double-blind
      study remained at similar levels between weeks 2 and 52 in patients who had
      previously taken istradefylline 20 and 40 mg/d in the preceding double-blind
      study. CONCLUSIONS: This study showed that istradefylline treatment was well
      tolerated and produced a sustained reduction in off time in levodopa-treated PD
      patients over a 52-week period.

PMID- 25768852
TI  - Pet killing as a manifestation of impulse control disorder secondary to
      pramipexol.
AB  - Impulse control disorders are frequent in Parkinson disease and are commonly
      associated with dopamine agonists intake. Typical manifestations include punding,
      hypersexuality, pathological gambling, and other compulsive behaviors. Symptoms
      often promptly disappear when dopamine agonists are discontinued, but if the
      origin is misinterpreted, symptoms may become a problem. We here report the case
      of a patient with juvenile Parkinson disease treated with 4.5 mg/d of pramipexol,
      who developed the need to adopt cats. He adopted almost 50 of them, but after he
      adopted them, he felt the need to kill them. The case became well known, and he
      became depressed and isolated. He was admitted to a psychiatric hospital and
      thought that he was a psychotic. However, when pramipexol was replaced by
      levodopa, the symptoms disappeared. This case illustrates the wide range of
      manifestations of impulse control disorders and warrants the inclusion of violent
      behaviors among them. 

PMID- 25768853
TI  - Writing tremor secondary to ischemic stroke: a report on a case with a remarkable
      response to topiramate.
AB  - Writing tremor (WT) is a task-specific tremor that occurs only or mostly while
      writing with the dominant hand. Secondary cases are extremely uncommon. We report
      on a patient who, after developing a WT after an ischemic stroke, had a
      remarkable response to topiramate (TPM). CASE: A 65-year-old right-handed man
      with a history of arterial hypertension, dyslipidemia, and coronary heart disease
      presented dizziness and headache followed by a loss of consciousness and then a
      right hemiparesis. He regained his strength on the fifth day. Fourteen days after
      stroke, he developed a WT as well as other complications with activities such as
      welding (he is a welder) and using a spoon. He was treated with 50 mg/d of TPM
      with marked improvement in WT. A few weeks after TPM was discontinued, the WT
      symptoms reappeared and he was retreated, showing the same beneficial
      reaction.Electromyographic record showed a 5- to 6-Hz tremor in his right hand,
      and a magnetic resonance imaging showed bilateral small frontoparietal
      subcortical infarcts. CONCLUSIONS: Primary WT pathophysiology is not well known,
      and secondary WT as a result of stroke is even less considered. Although patients
      with essential tremor benefit with TPM and WT could be a variant of essential
      tremor, we used TPM with our patient and there was a marked benefit.

PMID- 25768854
TI  - Methylphenidate-induced awake bruxism: a case report.
AB  - Methylphenidate (MPH) is a stimulant that is commonly used in the treatment of
      attention-deficit/hyperactivity disorder in children and adults. Several reports
      are available regarding the relationship of MPH use and sleep bruxism. We report
      the case of a 9-year-old boy who presented with severe awake bruxism after his
      second dose of sustained release form of MPH treatment, which was confirmed on
      rechallenge. This is the first report of its kind showing such relationship in
      the literature. 

PMID- 25768855
TI  - Amelioration of untreated restless legs syndrome by tadalafil in a patient with
      erectile dysfunction.

PMID- 25768856
TI  - Can cannabis cause psychosis?
AB  - In recent years, increasing popular support for the medicinal and recreational
      use of cannabis has led to legalization for both medicinal and recreational
      purposes in the United States. To the extent that these changes in policy lead to
      increase widespread use, it is important to consider the association between
      heavy chronic cannabis use and the onset of psychotic illnesses, such as
      schizophrenia. This article provides a brief review of evidence that support
      cannabis use as a risk factor in the complex etiology of psychotic illness. In
      addition to reviewing psychopharmacology, longitudinal research, and clinical
      studies, the article addresses the potential implications of current research on
      public health policy. 

PMID- 25768857
TI  - Serotonin syndrome with sertraline and methylphenidate in an adolescent.

PMID- 25768858
TI  - Efficacy of sildenafil in a patient with restless legs syndrome/Willis-Ekbom
      disease.

PMID- 25768859
TI  - Community-based sexually transmitted infection screening and increased detection
      of pharyngeal and urogenital Chlamydia trachomatis and Neisseria gonorrhoeae
      infections in female sex workers in Hong Kong.
AB  - BACKGROUND: Female sex workers (FSWs) are vulnerable to sexually transmitted
      infections (STIs) and are one of the key populations being infected most by
      Chlamydia trachomatis and Neisseria gonorrhoeae infections. In Hong Kong, limited
      data on the burden of chlamydial and gonococcal infections exist because regular
      screenings are not offered. This study aimed to investigate the prevalence of C.
      trachomatis and N. gonorrhoeae in FSWs and to assess predictors associated with
      unprotected fellatio. METHODS: A cross-sectional study was conduct on 340 FSWs
      attending a community organization for HIV/STI screening, and a questionnaire
      addressing sociodemographic and behavioral characteristics was administered to
      all FSWs. RESULTS: The prevalence of syphilis infection was 2.1%, and none was
      tested positive for HIV. The positivity for pharyngeal C. trachomatis and N.
      gonorrhoeae was 3.2% and 4.4%, respectively, whereas that for urogenital
      chlamydial and gonococcal infection was 10.6% and 0.9%, respectively. Of 313 FSWs
      offering fellatio, having unprotected fellatio with clients was significantly
      associated with the perceived low risk of contracting STI via fellatio (adjusted
      odds ratio [OR], 1.88), working in clubs (adjusted OR, 11.14), working on streets
      (adjusted OR, 3.28), recently started working in the sex industry for 1 year or
      less (adjusted OR, 3.05), and reporting group sex in the previous year (adjusted
      OR, 11.03). CONCLUSIONS: The prevalence of HIV and syphilis infection remains
      low. This study reveals a relatively high prevalence of N. gonorrhoeae detected
      mostly in the pharynx. Offering pharyngeal screening for STI would facilitate
      early diagnosis and treatment of gonococcal infection in FSWs in Hong Kong.

PMID- 25768860
TI  - Fibromyalgia survey criteria are associated with increased postoperative opioid
      consumption in women undergoing hysterectomy.
AB  - BACKGROUND: The current study was designed to test the hypothesis that the
      fibromyalgia survey criteria would be directly associated with increased opioid
      consumption after hysterectomy even when accounting for other factors previously
      described as being predictive for acute postoperative pain. METHODS: Two hundred
      eight adult patients undergoing hysterectomy between October 2011 and December
      2013 were phenotyped preoperatively with the use of validated self-reported
      questionnaires including the 2011 fibromyalgia survey criteria, measures of pain
      severity and descriptors, psychological measures, preoperative opioid use, and
      health information. The primary outcome was the total postoperative opioid
      consumption converted to oral morphine equivalents. RESULTS: Higher fibromyalgia
      survey scores were significantly associated with worse preoperative pain
      characteristics, including higher pain severity, more neuropathic pain, greater
      psychological distress, and more preoperative opioid use. In a multivariate
      linear regression model, the fibromyalgia survey score was independently
      associated with increased postoperative opioid consumption, with an increase of 7
      mg oral morphine equivalents for every 1-point increase on the 31-point measure
      (Estimate, 7.0; Standard Error, 1.7; P < 0.0001). In addition to the fibromyalgia
      survey score, multivariate analysis showed that more severe medical comorbidity,
      catastrophizing, laparotomy surgical approach, and preoperative opioid use were
      also predictive of increased postoperative opioid consumption. CONCLUSIONS: As
      was previously demonstrated in a total knee and hip arthroplasty cohort, this
      study demonstrated that increased fibromyalgia survey scores were predictive of
      postoperative opioid consumption in the posthysterectomy surgical population
      during their hospital stay. By demonstrating the generalizability in a second
      surgical cohort, these data suggest that patients with fibromyalgia-like
      characteristics may require a tailored perioperative analgesic regimen.

PMID- 25768861
TI  - Opioid Half-lives and Hemlines: The Long and Short of Fashion.

PMID- 25768863
TI  - Transfer printed silver nanowire transparent conductors for PbS-ZnO
      heterojunction quantum dot solar cells.
AB  - Transfer-printed silver nanowire transparent conducting electrodes are
      demonstrated in lead sulfide-zinc oxide quantum dot solar cells. Advantages of
      using this transparent conductor technology are increased junction surface
      energy, solution processing, and the potential cost reduction of low temperature
      processing. Joule heating, device aging, and film thickness effects are
      investigated to understand shunt pathways created by nanowires protruding
      perpendicular to the film. A V(oc) of 0.39 +/- 0.07 V, J(sc) of 16.2 +/- 0.2
      mA/cm(2), and power conversion efficiencies of 2.8 +/- 0.4% are presented.

PMID- 25768862
TI  - Association between socioeconomic status and pain, function and pain
      catastrophizing at presentation for total knee arthroplasty.
AB  - BACKGROUND: Patients with higher socioeconomic status (SES) are shown to have
      better total knee arthroplasty (TKA) outcomes compared to those with lower SES.
      The relationship between SES and factors that influence TKA use is understudied.
      We examined the association between SES and pain, function and pain
      catastrophizing at presentation for TKA. METHODS: In patients undergoing TKA at
      an academic center, we obtained preoperative pain and functional status (WOMAC
      Index 0-100, 100 worst), pain catastrophizing (PCS, >= 16 high), and mental
      health (MHI-5, <68 poor). We described individual-level SES using education as a
      proxy, and area-level SES using a validated composite index linking geocoded
      addresses to U.S. Census data. We measured associations between these indicators
      and pain, function and pain catastrophizing, adjusting for age, sex and BMI.
      RESULTS: Among 316 patients, mean age was 65.9 (SD 8.7), 59% were female, and 88%
      were Caucasian; 17% achieved less than college education and 62% were college
      graduates. The median area SES index score was 59 (U.S. median 51). Bivariable
      analyses demonstrated associations between higher individual- and area-level SES
      and lower pain, higher function and less pain catastrophizing (all p<0.05).
      Adjusted analyses demonstrated statistically significant associations between
      higher individual- and area-level SES and better function and less pain.
      CONCLUSION: In this cohort, patients with higher individual- and area-level SES
      had lower pain and higher function at the time of TKA than lower SES patients.
      Further research is needed to assess what constitutes appropriate levels of pain
      and function to undergo TKA in these higher SES groups.

PMID- 25768864
TI  - The impact of HIV care and support interventions on key outcomes in low- and
      middle-income countries: a literature review--introduction.

PMID- 25768866
TI  - TB screening among people living with HIV/AIDS in resource-limited settings.
AB  - Tuberculosis (TB) continues to be the leading cause of morbidity and mortality
      among people living with HIV (PLHIV), making improved prevention and treatment of
      HIV-associated TB critical to ensuring long-term survival of PLHIV. TB screening
      among PLHIV is central to implementation of the World Health Organization's 3 I's
      interventions for reducing the impact of the TB and HIV syndemics. Effective TB
      screening will result in the identification of PLHIV with presumptive TB disease
      (ie, those with a positive symptom screen who require appropriate evaluation,
      including the use of diagnostic tools such as the Xpert MTB/RIF assay) and those
      eligible for isoniazid preventive therapy (ie, those who have a negative clinical
      symptom screen or who have a positive screen but are found not to have TB
      disease). Identification of PLHIV with presumptive TB also facilitates
      implementation of basic administrative measures for TB infection control,
      including fast tracking of coughing patients and separation from noncoughing
      PLHIV to reduce TB transmission. By contributing to the early diagnosis of TB
      disease among PLHIV, TB screening is also critical to facilitate early initiation
      of antiretroviral treatment among PLHIV diagnosed with TB disease who might not
      otherwise be eligible for antiretroviral treatment based on CD4 count or clinical
      staging. TB screening thus serves as a gateway for multiple TB/HIV interventions
      and is an integral part of routine clinical services for PLHIV at each clinic
      visit. 

PMID- 25768865
TI  - Assessment of the impact of cotrimoxazole prophylaxis on key outcomes among HIV
      infected adults in low- and middle-income countries: a systematic review.
AB  - BACKGROUND: Cotrimoxazole (CTX) prophylaxis is among the key interventions
      provided to HIV-infected individuals in resource-limited settings. We conducted a
      systematic review of the available evidence. METHODS: MEDLINE, Embase, Global
      Health, CINAHL, SOCA, and African Index Medicus (AIM) were used to identify
      articles relevant to the CTX prophylaxis intervention from 1995 to 2014. Included
      articles addressed impact of CTX prophylaxis on the outcomes of mortality,
      morbidity, retention in care, quality of life, and/or prevention of ongoing HIV
      transmission. We rated the quality of evidence in individual articles and
      assessed the overall quality of the body of evidence, the expected impact, and
      the cost effectiveness (CE) for each outcome. RESULTS: Of the initial 1418
      identified articles, 42 met all inclusion criteria. These included 9 randomized
      controlled trials, 26 observational studies, 2 systematic reviews with meta
      analysis, 1 other systematic review, and 4 CE studies. The overall quality of
      evidence was rated as "good" and the expected impact "high" for both mortality
      and morbidity. The overall quality of evidence from the 4 studies addressing
      retention in care was rated as "poor," and the expected impact on retention was
      rated as "uncertain." The 4 assessed CE studies showed that provision of CTX
      prophylaxis is cost effective and sometimes cost saving. No studies addressed
      impact on quality of life or HIV transmission. CONCLUSIONS: CTX prophylaxis is a
      cost-effective intervention with expected high impact on morbidity and mortality
      reduction in HIV-infected adults in resource-limited settings. Benefits are seen
      in both pre-antiretroviral therapy and antiretroviral therapy populations.

PMID- 25768867
TI  - Prevalence of HIV and hepatitis B virus co-infection in sub-Saharan Africa and
      the potential impact and program feasibility of hepatitis B surface antigen
      screening in resource-limited settings.
AB  - BACKGROUND: Screening people living with HIV for hepatitis B virus (HBV) co
      infection is recommended in resource-rich settings to optimize HIV antiretroviral
      therapy (ART) and mitigate HBV-related liver disease. This review examines the
      need, feasibility, and impact of screening for HBV in resource-limited settings
      (RLS). METHODS: We searched 6 databases to identify peer-reviewed publications
      between 2007 and 2013 addressing (1) HIV/HBV co-infection frequency in sub
      Saharan Africa (SSA); (2) performance of hepatitis B surface antigen (HBsAg)
      rapid strip assays (RSAs) in RLS; (3) impact of HBV co-infection on morbidity,
      mortality, or liver disease progression; and/or (4) impact of HBV-suppressive
      antiretroviral medications as part of ART on at least one of 5 outcomes
      (mortality, morbidity, HIV transmission, retention in HIV care, or quality of
      life). We rated the quality of individual articles and summarized the body of
      evidence and expected impact of each intervention per outcome addressed. RESULTS:
      Of 3940 identified studies, 85 were included in the review: 55 addressed HIV/HBV
      co-infection frequency; 6 described HBsAg RSA performance; and 24 addressed the
      impact of HIV/HBV co-infection and ART. HIV/HBV frequency in sub-Saharan Africa
      varied from 0% to >28.4%. RSA performance in RLS showed good, although variable,
      sensitivity and specificity. Quality of studies ranged from strong to weak.
      Overall quality of evidence for the impact of HIV/HBV co-infection and ART on
      morbidity and mortality was fair and good to fair, respectively. CONCLUSIONS:
      Combined, the body of evidence reviewed suggests that HBsAg screening among
      people living with HIV could have substantial impact on preventing morbidity and
      mortality among HIV/HBV co-infected individuals in RLS.

PMID- 25768869
TI  - Use of isoniazid preventive therapy for tuberculosis prophylaxis among people
      living with HIV/AIDS: a review of the literature.
AB  - BACKGROUND: Tuberculosis (TB) is the leading preventable cause of death in
      persons living with HIV (PLHIV), accounting for over a quarter of all HIV
      associated deaths in 2012. Isoniazid preventive therapy (IPT) has the potential
      to decrease TB-related cases and deaths in PLHIV; however, implementation of this
      has been slow in many high HIV- and TB-burden settings. METHODOLOGY: We performed
      an assessment of the evidence for the use of IPT in adults living with HIV based
      on a review of the literature published from 1995 to 2013. Eligible articles
      included data on mortality, morbidity, or retention in care related to the
      provision of IPT to adults with HIV in low- or middle-income countries. Cost
      effectiveness information was also abstracted. RESULTS: We identified 41 articles
      involving over 45,000 PLHIV. While there was little evidence to demonstrate that
      IPT reduced mortality in PLHIV, there was substantial evidence that IPT reduced
      TB incidence. While these findings were consistent irrespective of CD4 or
      antiretroviral therapy status, studies frequently demonstrated a greater benefit
      among patients with a positive TB skin test (TST). Duration of effectiveness and
      benefits of prolonged therapy varied across settings. CONCLUSIONS: This analysis
      supports World Health Organization recommendations for the provision of IPT to
      PLHIV to reduce TB-associated morbidity and serves to highlight the need to
      strengthen IPT implementation. While there appears to be a greater benefit of IPT
      among PLHIV who are TST positive, IPT should be provided to all PLHIV without
      presumptive TB when TST is not available.

PMID- 25768868
TI  - Integrating prevention interventions for people living with HIV into care and
      treatment programs: a systematic review of the evidence.
AB  - INTRODUCTION: This review assesses the impact of prevention interventions for
      people living with HIV on HIV-related mortality, morbidity, retention in care,
      quality of life, and prevention of ongoing HIV transmission in resource-limited
      settings (RLSs). METHODS: We conducted a systematic review of studies reporting
      the results of prevention interventions for people living with HIV in RLS
      published between January 2000 and August 2014. Standardized methods of searching
      and data abstraction were used. RESULTS: Ninety-two studies met the eligibility
      criteria: 24 articles related to adherence counseling and support, 13 on risk
      reduction education and condom provision, 19 on partner HIV testing and
      counseling, 14 on provision of family planning services, and 22 on assessment and
      treatment of other sexually transmitted infections. Findings indicate good
      evidence that adherence counseling and sexually transmitted infection treatment
      can have a high impact on morbidity, whereas risk reduction education, partner
      HIV testing and counseling, and family planning counseling can prevent
      transmission of HIV. More limited evidence was found to support the impact of
      these interventions on retention in care and quality of life. Most studies did
      not report cost information, making it difficult to draw conclusions about the
      cost-effectiveness of these interventions. CONCLUSIONS: This evidence suggests
      that these prevention interventions, if brought to sufficient scale and coverage,
      can help support and optimize the impact of core treatment and prevention
      interventions in RLS. Further operational research with more rigorous study
      designs, and ideally with biomarkers and costing information, is needed to
      determine the best model for providing these interventions in RLS.

PMID- 25768871
TI  - The impact of water, sanitation, and hygiene interventions on the health and well
      being of people living with HIV: a systematic review.
AB  - BACKGROUND: Access to improved water supply and sanitation is poor in low-income
      and middle-income countries. Persons living with HIV/AIDS (PLHIV) experience more
      severe diarrhea, hospitalizations, and deaths from diarrhea because of waterborne
      pathogens than immunocompetent populations, even when on antiretroviral therapy
      (ART). METHODS: We examined the existing literature on the impact of water,
      sanitation, and hygiene (WASH) interventions on PLHIV for these outcomes: (1)
      mortality, (2) morbidity, (3) retention in HIV care, (4) quality of life, and (5)
      prevention of ongoing HIV transmission. Cost-effectiveness was also assessed.
      Relevant abstracts and articles were gathered, reviewed, and prioritized by
      thematic outcomes of interest. Articles meeting inclusion criteria were
      summarized in a grid for comparison. RESULTS: We reviewed 3355 citations,
      evaluated 132 abstracts, and read 33 articles. The majority of the 16 included
      articles focused on morbidity, with less emphasis on mortality. Contaminated
      water, lack of sanitation, and poor hygienic practices in homes of PLHIV increase
      the risk of diarrhea, which can result in increased viral load, decreased CD4
      counts, and reduced absorption of nutrients and antiretroviral medication. We
      found WASH programming, particularly water supply, household water treatment, and
      hygiene interventions, reduced morbidity. Data were inconclusive on mortality.
      Research gaps remain in retention in care, quality of life, and prevention of
      ongoing HIV transmission. Compared with the standard threshold of 3 times GDP per
      capita, WASH interventions were cost-effective, particularly when incorporated
      into complementary programs. CONCLUSIONS: Although research is required to
      address behavioral aspects, evidence supports that WASH programming is beneficial
      for PLHIV.

PMID- 25768870
TI  - Impact of cotrimoxazole and insecticide-treated nets for malaria prevention on
      key outcomes among HIV-infected adults in low- and middle-income countries: a
      systematic review.
AB  - BACKGROUND: HIV-infected adults are at increased risk of severe malaria and
      death. Malaria prevention in people living with HIV (PLHIV) consists of several
      interventions, including cotrimoxazole (CTX) prophylaxis and insecticide-treated
      nets (ITNs). We conducted a systematic review of the available evidence. METHODS:
      MEDLINE, EmBase, Global Health, CINAHL, SOCA, and African Index Medicus were used
      to identify articles relevant to the CTX prophylaxis and ITNs interventions from
      1995 to July 2014. For each individual study, we assessed the quality of evidence
      and the impact of the 2 interventions on the outcomes of mortality, morbidity,
      retention in care, quality of life, and/or prevention of ongoing HIV
      transmission. For each outcome, we summarized the quality of the overall body of
      evidence, the expected impact, and costing and cost-effectiveness (CE). FINDINGS:
      The overall quality of evidence regarding malaria-related morbidity was rated as
      "good" for CTX prophylaxis and "fair" for ITN use; the expected "impact" of these
      interventions on morbidity was rated "high" and "uncertain," respectively. Three
      studies that addressed the costing and CE of ITN provision for malaria prevention
      in PLHIV consisted of 2 full "level 1" and 1 partial "level 2" economic
      evaluations. CONCLUSIONS: CTX prophylaxis is effective in reducing malaria
      related morbidity among PLHIV. Limited evidence is available with respect to the
      impact and the CE of ITN use and/or provision in this population.

PMID- 25768872
TI  - Cryptococcal antigen screening and early antifungal treatment to prevent
      cryptococcal meningitis: a review of the literature.
AB  - BACKGROUND: Screening individuals with AIDS for serum cryptococcal antigen
      (CrAg), followed by treatment of CrAg positives with antifungals, may prevent
      cryptococcal meningitis. This review examined data on CrAg screening and
      treatment in resource-limited settings. METHODS: We searched articles published
      during 2007-2014 on the effectiveness and cost-effectiveness of CrAg screening
      and treatment on the outcomes of mortality, morbidity, retention in care, quality
      of life, and/or prevention of ongoing HIV transmission. We rated overall quality
      of individual articles, summarized the body of evidence, the expected impact, and
      cost-effectiveness for each outcome. RESULTS: We identified 2613 articles. Eight
      met all inclusion criteria. Five studies addressed mortality and/or morbidity
      outcomes; all were observational and had small sample sizes; 3 lacked a
      comparison group. Ratings of study quality ranged from "medium" to "weak," and
      the quality of the overall body of evidence for mortality and morbidity outcomes
      was rated as "fair." The intervention's expected impact on mortality and
      morbidity was rated as "moderate." The 4 cost-effectiveness studies included in
      the analysis showed that CrAg screening and treatment interventions are highly
      cost-effective. No studies addressed retention in care, quality of life, or HIV
      transmission. CONCLUSIONS: Although limited, the body of evidence regarding CrAg
      screening and treatment suggests that the intervention may have an impact on
      preventing cryptococcal meningitis and death in persons with AIDS. Additional
      research is needed to quantify the intervention's effectiveness and identify
      optimal treatment dosing and implementation best practices.

PMID- 25768874
TI  - A systematic review of the effects of visual inspection with acetic acid,
      cryotherapy, and loop electrosurgical excision procedures for cervical dysplasia
      in HIV-infected women in low- and middle-income countries.
AB  - BACKGROUND: Cervical cancer, almost all of which is caused by human
      papillomavirus, accounts for 12% of female cancers worldwide and is more common
      among HIV-infected women. Nine of 10 deaths from cervical cancer occur in low-
      and middle-income countries (LMICs). Simple screening methods and outpatient
      treatment of precursor lesions save lives but the benefit of these interventions
      among HIV-infected women is uncertain. OBJECTIVE: We reviewed evidence of the
      effects of screening with visual inspection with acetic acid (VIA), and
      outpatient treatment for cervical precancer among HIV-infected women in LMIC.
      METHODS: A systematic review of articles published from January 1995 through July
      2013 was conducted using key terms for VIA cervical screening, cervical precancer
      treatment with cryotherapy or loop electrosurgical excision procedure, HIV
      infected women, low-resource settings, and outcomes, including morbidity and
      mortality. RESULTS: Of 2159 articles screened, 14 met inclusion criteria; all
      considered only morbidity outcomes. No articles dealt with the long-term impact
      of screening/treatment on cervical cancer incidence or mortality among HIV
      infected women. Articles reported on performance of VIA, prevalence of cervical
      dysplasia, and complications and rates of recurrent dysplasia after treatment.
      CONCLUSIONS: Dysplasia prevalence and recurrence were higher among HIV-infected
      compared with HIV-uninfected women but morbidity from treatment was similar. Few
      data exist on long-term outcomes of VIA, cryotherapy, or loop electrosurgical
      excision procedure interventions among HIV-infected women in LMIC; longer-term
      outcomes research is needed to assess the effects of VIA or other screening
      modalities and outpatient treatment on prevention of cervical cancer among HIV
      infected women.

PMID- 25768873
TI  - Nutrition assessment, counseling, and support interventions to improve health
      related outcomes in people living with HIV/AIDS: a systematic review of the
      literature.
AB  - BACKGROUND: Although numerous studies have shown that severe to moderate wasting
      at the time of antiretroviral therapy initiation is strongly predictive of
      mortality, it remains unclear whether nutritional interventions at or before
      antiretroviral therapy initiation will improve outcomes. This review examines
      data on nutrition assessment, counseling, and support interventions in resource
      limited settings. METHODS: We identified articles published between 2005 and 2014
      on the effectiveness of nutrition assessment, counseling, and support
      interventions, particularly its impact on 5 outcomes: mortality, morbidity,
      retention in care, quality of life, and/or prevention of ongoing HIV
      transmission. We rated the overall quality of individual articles and summarized
      the body of evidence and expected impact for each outcome. RESULTS: Twenty-one
      articles met all inclusion criteria. The overall quality of evidence was weak,
      predominantly because of few studies being designed to directly address the
      question of interest. Only 2 studies were randomized trials with no food support
      control groups. The remainder were randomized studies of one type of food support
      versus another, cohort (nonrandomized) studies, or single-arm studies. Ratings of
      individual study quality ranged from "medium" to "weak," and the quality of the
      overall body of evidence ranged from "fair" to "poor." We rated the expected
      impact on all outcomes as "uncertain." CONCLUSIONS: Rigorous better designed
      studies in resource-limited settings are urgently needed to understand the
      effectiveness of nutrition assessment and counseling alone, as well as studies to
      understand better modalities of food support (targeting, timing, composition,
      form, and duration) to improve both short- and long-term patient retention in
      care and treatment, and clinical outcomes.

PMID- 25768875
TI  - The impact of social services interventions in developing countries: a review of
      the evidence of impact on clinical outcomes in people living with HIV.
AB  - BACKGROUND: Social service interventions have been implemented in many countries
      to help people living with HIV (PLHIV) and household members cope with economic
      burden as a result of reduced earning or increased spending on health care.
      However, the evidence for specific interventions-economic strengthening and legal
      services-on key health outcomes has not been appraised. METHODS: We searched
      electronic databases from January 1995 to May 2014 and reviewed relevant
      literature from resource-limited settings on the impact of social service
      interventions on mortality, morbidity, retention in HIV care, quality of life,
      and ongoing HIV transmission and their cost-effectiveness. RESULTS: Of 1685
      citations, 8 articles reported the health impact of economic strengthening
      interventions among PLHIV in resource-limited settings. None reported on legal
      services. Six of the 8 studies were conducted in sub-Saharan Africa: 1 reported
      on all 5 outcomes and 2 reported on 4 and 2 outcomes, respectively. The remaining
      5 reported on 1 outcome each. Seven studies reported on quality of life. Although
      all studies reported some association between economic strengthening
      interventions and HIV care outcomes, the quality of evidence was rated fair or
      poor because studies were of low research rigor (observational or qualitative),
      had small sample size, or had other limitations. The expected impact of economic
      strengthening interventions was rated as high for quality of life but uncertain
      for all the other outcomes. CONCLUSIONS: Implementation of economic strengthening
      interventions is expected to have a high impact on the quality of life for PLHIV
      but uncertain impact on mortality, morbidity, retention in care, and HIV
      transmission. More rigorous research is needed to explore the impact of more
      targeted intervention components on health outcomes.

PMID- 25768876
TI  - Impact of support groups for people living with HIV on clinical outcomes: a
      systematic review of the literature.
AB  - BACKGROUND: Support groups for people living with HIV are integrated into HIV
      care and treatment programs as a modality for increasing patient literacy and as
      an intervention to address the psychosocial needs of patients. However, the
      impact of support groups on key health outcomes has not been fully determined.
      METHODS: We searched electronic databases from January 1995 through May 2014 and
      reviewed relevant literature on the impact of support groups on mortality,
      morbidity, retention in HIV care, quality of life (QOL), and ongoing HIV
      transmission, as well as their cost-effectiveness. RESULTS: Of 1809 citations
      identified, 20 met the inclusion criteria. One reported on mortality, 7 on
      morbidity, 5 on retention in care, 7 on QOL, and 7 on ongoing HIV transmission.
      Eighteen (90%) of the articles reported largely positive results on the impact of
      support group interventions on key outcomes. Support groups were associated with
      reduced mortality and morbidity, increased retention in care, and improved QOL.
      Because of study limitations, the overall quality of evidence was rated as fair
      for mortality, morbidity, retention in care, and QOL, and poor for HIV
      transmission. CONCLUSIONS: Implementing support groups as an intervention is
      expected to have a high impact on morbidity and retention in care and a moderate
      impact on mortality and QOL of people living with HIV. Support groups improve
      disclosure with potential prevention benefits but the impact on ongoing
      transmission is uncertain. It is unclear whether this intervention is cost
      effective given the paucity of studies in this area.

PMID- 25768877
TI  - Prioritizing HIV care and support interventions-moving from evidence to policy.

PMID- 25768878
TI  - Extensive facial sclerosing lipogranulomatosis as a complication of cosmetic
      acupuncture.

PMID- 25768879
TI  - Malignant hidroacanthoma simplex treated with Mohs surgery.

PMID- 25768880
TI  - Only conflicts of interest?
AB  - The current situation of the biomedical sciences is critically discussed. It can
      be summarized as follows: 1. We have to acknowledge the presence of a serious
      credibility problem, which might undermine the foundations of medical science.
      ("Sliding on a slippery slope") 2. Multiple forces going beyond simple conflicts
      of interest push medical science further down the slippery slope. ("Who is
      pushing?") 3. The public awareness of something seriously wrong with medical
      science is mounting on all levels of our multimedia society. ("Looking into the
      media mirror") 4. Technical corrective measures may be easily implemented,
      however, to change an expanding and "successful" science culture actually
      destroying it's own foundations will need a sustained effort by the medical and
      scientific community on all levels. ("Look away--or act?").

PMID- 25768881
TI  - Physiology of layer 5 pyramidal neurons in mouse primary visual cortex:
      coincidence detection through bursting.
AB  - L5 pyramidal neurons are the only neocortical cell type with dendrites reaching
      all six layers of cortex, casting them as one of the main integrators in the
      cortical column. What is the nature and mode of computation performed in mouse
      primary visual cortex (V1) given the physiology of L5 pyramidal neurons? First,
      we experimentally establish active properties of the dendrites of L5 pyramidal
      neurons of mouse V1 using patch-clamp recordings. Using a detailed multi
      compartmental model, we show this physiological setup to be well suited for
      coincidence detection between basal and apical tuft inputs by controlling the
      frequency of spike output. We further show how direct inhibition of calcium
      channels in the dendrites modulates such coincidence detection. To establish the
      singe-cell computation that this biophysics supports, we show that the
      combination of frequency-modulation of somatic output by tuft input and
      (simulated) calcium-channel blockage functionally acts as a composite sigmoidal
      function. Finally, we explore how this computation provides a mechanism whereby
      dendritic spiking contributes to orientation tuning in pyramidal neurons. 

PMID- 25768882
TI  - Hip dislocation following minor trauma in a patient with neurofibromatosis type
      1: a case report and review of the literature.
AB  - Neurofibromatosis type 1 (NF-1) is a common autosomal dominant disorder which is
      known to have associated skeletal manifestations. There are documented cases of
      hip dislocation in NF-1, although it is a rare occurrence. Previous cases have
      been associated with intra-articular neurofibromas, acetabular protrusio and
      femoral deformities such as coxa valga and in one case increased femoral
      offset.The authors review the literature on pelvic manifestations and report a
      case of hip dislocation in a 19-year-old woman with neurofibromatosis-one
      following minor trauma believed to be secondary to markedly increased femoral
      offset.This case illustrates the effect the NF-1 can have on the anatomy of the
      proximal femur and one of the complications that can present to the orthopaedic
      surgeon, without the presence on an intra-articular neurofibroma. In a review of
      the literature the authors found only two other cases of hip dislocation
      associated with NF-1 that occurred without the presence of an intra-articular
      neurofibroma. 

PMID- 25768883
TI  - Organochlorine pesticides and polychlorinated biphenyls in air, grass and yak
      butter from Namco in the central Tibetan Plateau.
AB  - Limited studies on bioaccumulation of persistent organic pollutants (POPs) along
      terrestrial food chains were conducted. The food chain air-grass-yak (butter) in
      the pasture region of Namco in the central Tibetan Plateau (TP) was chosen for
      study. The air, grass and butter POPs in the TP were at the lower end of the
      concentrations generally found around the globe. HCB was the main pollutant in
      air and butter. Besides HCB, beta-HCH and p,p'-DDE were the other major compounds
      in butter. Along the food chain, DDTs and high molecular weight PCB-138, 153 and
      180 had higher Biological Concentration Factor values. The air-butter transfer
      factors of POPs were derived and demonstrated the practical advantage in
      predicting the atmospheric OCPs and PCBs to the TP. This study sheds light on the
      transfer and accumulation of POPs along the terrestrial food chain of the TP. 

PMID- 25768884
TI  - Enhanced photosynthetic capacity and antioxidant potential mediate
      brassinosteriod-induced phenanthrene stress tolerance in tomato.
AB  - Photosynthesis, the basal manufacturing process in the earth is habitually
      restricted by airborne micropollutants such as phenanthrene (PHE). Here, we show
      that 24-epibrassinolide (EBR), a bioactive plant steroid is able to keep higher
      photosynthetic capacity consistently for a long period under a shoot-imposed PHE
      stress in tomato. EBR-promoted photosynthetic capacity and efficiency eventually
      resulted in a 37.5% increase of biomass under PHE stress. As primary response,
      transcripts of antioxidant genes were remarkably induced by EBR in PHE-treated
      plants. Activities of antioxidant and detoxification enzymes were also enhanced
      by EBR. Notably, EBR-induced higher antioxidant potential was associated with
      reduced levels of H2O2 and O2(-), resulting in a 32.7% decrease of content of
      malondialdehyde in the end of experiment and relatively healthy chloroplast
      ultrastructure in EBR + PHE treatment compared with PHE alone. These results
      indicate that EBR alleviates shoot-imposed PHE phytotoxicity by maintaining a
      consistently higher photosynthetic capacity and antioxidant potential in tomato. 

PMID- 25768885
TI  - Bayesian network models for error detection in radiotherapy plans.
AB  - The purpose of this study is to design and develop a probabilistic network for
      detecting errors in radiotherapy plans for use at the time of initial plan
      verification. Our group has initiated a multi-pronged approach to reduce these
      errors. We report on our development of Bayesian models of radiotherapy plans.
      Bayesian networks consist of joint probability distributions that define the
      probability of one event, given some set of other known information. Using the
      networks, we find the probability of obtaining certain radiotherapy parameters,
      given a set of initial clinical information. A low probability in a propagated
      network then corresponds to potential errors to be flagged for investigation. To
      build our networks we first interviewed medical physicists and other domain
      experts to identify the relevant radiotherapy concepts and their associated
      interdependencies and to construct a network topology. Next, to populate the
      network's conditional probability tables, we used the Hugin Expert software to
      learn parameter distributions from a subset of de-identified data derived from a
      radiation oncology based clinical information database system. These data
      represent 4990 unique prescription cases over a 5 year period. Under test case
      scenarios with approximately 1.5% introduced error rates, network performance
      produced areas under the ROC curve of 0.88, 0.98, and 0.89 for the lung, brain
      and female breast cancer error detection networks, respectively. Comparison of
      the brain network to human experts performance (AUC of 0.90 +/- 0.01) shows the
      Bayes network model performs better than domain experts under the same test
      conditions. Our results demonstrate the feasibility and effectiveness of
      comprehensive probabilistic models as part of decision support systems for
      improved detection of errors in initial radiotherapy plan verification
      procedures. 

PMID- 25768886
TI  - Encoded libraries of chemically modified peptides.
AB  - The use of powerful technologies for generating and screening DNA-encoded protein
      libraries has helped drive the development of proteins as pharmaceutical ligands.
      However the development of peptides as pharmaceutical ligands has been more
      limited. Although encoded peptide libraries are typically several orders of
      magnitude larger than classical chemical libraries, can be more readily screened,
      and can give rise to higher affinity ligands, their use as pharmaceutical ligands
      is limited by their intrinsic properties. Two of the intrinsic limitations
      include the rotational flexibility of the peptide backbone and the limited number
      (20) of natural amino acids. However these limitations can be overcome by use of
      chemical modification. For example, the libraries can be modified to introduce
      topological constraints such as cyclization linkers, or to introduce new chemical
      entities such as small molecule ligands, fluorophores and photo-switchable
      compounds. This article reviews the chemistry involved, the properties of the
      peptide ligands, and the new opportunities offered by chemical modification of
      DNA-encoded peptide libraries. 

PMID- 25768888
TI  - Enhanced photo-Fenton degradation of rhodamine B using graphene oxide-amorphous
      FePO4 as effective and stable heterogeneous catalyst.
AB  - A series of graphene oxide (GO)-FePO4 composites with different GO weight ratios
      (2.5%, 5%, 10%, w/w) were prepared using a simple precipitation process and were
      firstly used as heterogeneous photo-Fenton catalysts. FESEM images prove the
      loose structure of the 5GO-FePO4 composite. UV-vis analysis demonstrates that the
      introduction of GO could enhance solar energy utilization of the composites.
      Under visible light irradiation, the degradation rate of rhodamine B (RhB) by the
      5GO-FePO4 composite was 2.87 times more than that by the pure FePO4 in the
      presence of hydrogen peroxide. The composite was highly effective for the
      degradation of RhB in a wide pH range of 2.18-10.40 with negligible iron
      leaching. Moreover, the composite still showed high catalytic activity after six
      cycles, which makes it a promising heterogeneous catalyst for wastewater
      treatment. The introduction of GO promotes the photo-Fenton reaction of GO-FePO4
      via three roles: offering more active sites, increasing adsorption capacity and
      accelerating the Fe(3+)/Fe(2+) cycle by improving the utilization of solar
      energy. Our work may provide new insights for the development of new effective
      heterogeneous photo-Fenton catalyst. 

PMID- 25768887
TI  - The impact of a register on the management of neonatal cooling in Switzerland.
AB  - BACKGROUND: Therapeutic hypothermia following hypoxic ischaemic encephalopathy in
      term infants was introduced into Switzerland in 2005. Initial documentation of
      perinatal and resuscitation details was poor and neuromonitoring insufficient. In
      2011, a National Asphyxia and Cooling Register was introduced. AIMS: To compare
      management of cooled infants before and after introduction of the register
      concerning documentation, neuromonitoring, cooling methods and evaluation of
      temperature variability between cooling methods. STUDY DESIGN: Data of cooled
      infants before the register was in place (first time period: 2005-2010) and
      afterwards (second time period: 2011-2012) was collected with a case report form.
      RESULTS: 150 infants were cooled during the first time period and 97 during the
      second time period. Most infants were cooled passively or passively with gel
      packs during both time periods (82% in 2005-2010 vs 70% in 2011-2012), however
      more infants were cooled actively during the second time period (18% versus 30%).
      Overall there was a significant reduction in temperature variability (p < 0.001)
      comparing the two time periods. A significantly higher proportion of temperature
      measurements within target temperature range (72% versus 77%, p < 0.001), fewer
      temperature measurements above (24% versus 7%, p < 0.001) and more temperatures
      below target range (4% versus 16%, p < 0.001) were recorded during the second
      time period. Neuromonitoring improved after introduction of the cooling register.
      CONCLUSION: Management of infants with HIE improved since introducing the
      register. Temperature variability was reduced, more temperature measurements in
      the target range and fewer temperature measurements above target range were
      observed. Neuromonitoring has improved, however imaging should be performed more
      often.

PMID- 25768889
TI  - Event-triggered asynchronous intermittent communication strategy for
      synchronization in complex dynamical networks.
AB  - This paper presents a new framework for synchronization of complex network by
      introducing a mechanism of event-triggering distributed sampling information. A
      kind of event which avoids continuous communication between neighboring nodes is
      designed to drive the controller update of each node. The advantage of the event
      triggering strategy is the significant decrease of the number of controller
      updates for synchronization task of complex networks involving embedded
      microprocessors with limited on-board resources. To describe the system's ability
      reaching synchronization, a concept about generalized algebraic connectivity is
      introduced for strongly connected networks and then extended to the strongly
      connected components of the directed network containing a directed spanning tree.
      Two sufficient conditions are presented to reveal the underlying relationships of
      corresponding parameters to reach global synchronization based on algebraic
      graph, matrix theory and Lyapunov control method. A positive lower bound for
      inter-event times is derived to guarantee the absence of Zeno behavior. Finally,
      a numerical simulation example is provided to demonstrate the theoretical
      results. 

PMID- 25768890
TI  - Specific functions of the Rep and Rep' proteins of porcine circovirus during copy
      release and rolling-circle DNA replication.
AB  - The roles of two porcine circovirus replication initiator proteins, Rep and Rep',
      in generating copy-release and rolling-circle DNA replication intermediates were
      determined. Rep uses the supercoiled closed-circular genome (ccc) to initiate
      leading-strand synthesis (identical to copy-release replication) and generates
      the single-stranded circular (ssc) genome from the displaced DNA strand. In the
      process, a minus-genome primer (MGP) necessary for complementary-strand
      synthesis, from ssc to ccc, is synthesized. Rep' cleaves the growing nascent
      strand to regenerate the parent ccc molecule. In the process, a Rep'-DNA hybrid
      containing the right palindromic sequence (at the origin of DNA replication) is
      generated. Analysis of the virus particle showed that it is composed of four
      components: ssc, MGP, capsid protein and a novel Rep-related protein (designated
      Protein-3). 

PMID- 25768891
TI  - Porcine reproductive and respiratory syndrome virus nonstructural protein 2
      (nsp2) topology and selective isoform integration in artificial membranes.
AB  - The membrane insertion and topology of nonstructural protein 2 (nsp2) of porcine
      reproductive and respiratory syndrome virus (PRRSV) strain VR-2332 was assessed
      using a cell free translation system in the presence or absence of artificial
      membranes. Expression of PRRSV nsp2 in the absence of all other viral factors
      resulted in the genesis of both full-length nsp2 as well as a select number of C
      terminal nsp2 isoforms. Addition of membranes to the translation stabilized the
      translation reaction, resulting in predominantly full-length nsp2 as assessed by
      immunoprecipitation. Analysis further showed full-length nsp2 strongly associates
      with membranes, along with two additional large nsp2 isoforms. Membrane
      integration of full-length nsp2 was confirmed through high-speed density
      fractionation, protection from protease digestion, and immunoprecipitation. The
      results demonstrated that nsp2 integrated into the membranes with an unexpected
      topology, where the amino (N)-terminal (cytoplasmic) and C-terminal (luminal)
      domains were orientated on opposite sides of the membrane surface. 

PMID- 25768892
TI  - Galectin-3 plays a role in minute virus of mice infection.
AB  - Galectin-3 has previously been found to be required by the parvovirus minute
      virus of mice prototype strain (MVMp) for infection of mouse fibroblast cells.
      Since MVMp is an oncotropic virus, and galectin-3 is a multifunctional protein
      implicated in cancer metastasis, we hypothesized that galectin-3 and Mgat5, the
      Golgi enzyme that synthesizes high-affinity glycan ligands of galectin-3, might
      play a role in MVMp infection. Using siRNA-mediated knockdown of galectin-3 in
      mouse cells transformed with polyomavirus middle T antigen and Mgat5(-/-) mouse
      mammary tumor cells, we found that galectin-3 and Mgat5 are both necessary for
      efficient MVMp cell entry and infection, but not for cell binding. Moreover, we
      found that human cancer cells expressing higher levels of galectin-3 were more
      efficiently infected with MVMp than cell lines expressing lower galectin-3
      levels. We conclude that galectin-3 and Mgat5 are involved in MVMp infection, and
      propose that galectin-3 is a determinant of MVMp oncotropism. 

PMID- 25768893
TI  - Evidence-driven, patient-specific approaches for optimizing survival prolongation
      in breast cancer.

PMID- 25768897
TI  - On the morphology of cellulose nanofibrils obtained by TEMPO-mediated oxidation
      and mechanical treatment.
AB  - The morphological properties of cellulose nanofibrils obtained from eucalyptus
      pulp fibres were assessed. Two samples were produced with the same chemical
      treatment (NaClO/NaBr/TEMPO (2,2,6,6-tetramethylpiperidine-1-oxyl radical)
      oxidation), but distinct mechanical treatment intensities during homogenization.
      It was shown that the nanofibrils production yield increases with the mechanical
      energy. The effect of mechanical treatment on the yield was confirmed by laser
      profilometry of air-dried nanocellulose films. However, no significant
      differences were detected regarding the nanofibrils width as measured by atomic
      force microscopy (AFM) of air-dried films. On the other hand, differences in size
      were found either by laser diffraction spectroscopy or by dynamic light
      scattering (DLS) of the cellulose nanofibrils suspensions as a consequence of the
      differences in the length distribution of both samples. The nanofibrils length of
      the more nanofibrillated sample was calculated based on the width measured by AFM
      and the hydrodynamic diameter obtained by DLS. A length value of ca. 600 nm was
      estimated. The DLS hydrodynamic diameter, as an equivalent spherical diameter,
      was used to estimate the nanofibrils length assuming a cylinder with the same
      volume and with the diameter (width) assessed by AFM. A simple method is thus
      proposed to evaluate the cellulose nanofibrils length combining microscopy and
      light scattering methods.

PMID- 25768898
TI  - A molecular take on Aesop's The oak and the reeds.
AB  - Ngo et al. use single-molecule methods to show that DNA can be more readily
      displaced from one side of a nucleosome relative to the other side. This
      unexpected mechanical asymmetry may offer a path of least resistance, allowing
      RNA polymerases to traverse nucleosomes if they approach from the correct
      direction.

PMID- 25768899
TI  - Mitosis, diffusible crosslinkers, and the ideal gas law.
AB  - During mitosis, molecular motors hydrolyze ATP to generate sliding forces between
      adjacent microtubules and form the bipolar mitotic spindle. Lansky et al. now
      show that the diffusible microtubule crosslinker Ase1p can generate sliding
      forces between adjacent microtubules, and it does so without ATP hydrolysis.

PMID- 25768900
TI  - Transcription gets to the checkpoint.
AB  - The rapid cell proliferation characteristic of early animal embryos is
      accomplished with an abbreviated cell cycle and no DNA replication checkpoint.
      Blythe and Wieschaus provide evidence that nascent zygotic transcription precedes
      and may trigger-this checkpoint at the midblastula transition.

PMID- 25768901
TI  - Cold tolerance encoded in one SNP.
AB  - Cold tolerance fundamentally affects world crop harvest. Ma et al. now identify a
      single-nucleotide polymorphism in a gene called COLD1 that confers cold tolerance
      in japonica rice. This study reveals important insights into agronomical traits
      that are essential for human nutrition.

PMID- 25768902
TI  - Monkeys in a prisoner's dilemma.
AB  - Haroush and Williams trained pairs of monkeys to play in a prisoner's dilemma
      game, a model of social interactions. Recording from the dorsal anterior
      cingulate cortex (dACC), they find neurons whose activity reflects the
      anticipation of the opponent's yet unknown choice, which may be important in
      guiding animals' performance in the game. 

PMID- 25768903
TI  - The role of chromosome domains in shaping the functional genome.
AB  - The genome must be highly compacted to fit within eukaryotic nuclei but must be
      accessible to the transcriptional machinery to allow appropriate expression of
      genes in different cell types and throughout developmental pathways. A growing
      body of work has shown that the genome, analogously to proteins, forms an
      ordered, hierarchical structure that closely correlates and may even be causally
      linked with regulation of functions such as transcription. This review describes
      our current understanding of how these functional genomic "secondary and tertiary
      structures" form a blueprint for global nuclear architecture and the potential
      they hold for understanding and manipulating genomic regulation. 

PMID- 25768904
TI  - Human disease modeling reveals integrated transcriptional and epigenetic
      mechanisms of NOTCH1 haploinsufficiency.
AB  - The mechanisms by which transcription factor haploinsufficiency alters the
      epigenetic and transcriptional landscape in human cells to cause disease are
      unknown. Here, we utilized human induced pluripotent stem cell (iPSC)-derived
      endothelial cells (ECs) to show that heterozygous nonsense mutations in NOTCH1
      that cause aortic valve calcification disrupt the epigenetic architecture,
      resulting in derepression of latent pro-osteogenic and -inflammatory gene
      networks. Hemodynamic shear stress, which protects valves from calcification in
      vivo, activated anti-osteogenic and anti-inflammatory networks in NOTCH1(+/+),
      but not NOTCH1(+/-), iPSC-derived ECs. NOTCH1 haploinsufficiency altered H3K27ac
      at NOTCH1-bound enhancers, dysregulating downstream transcription of more than
      1,000 genes involved in osteogenesis, inflammation, and oxidative stress.
      Computational predictions of the disrupted NOTCH1-dependent gene network revealed
      regulatory nodes that, when modulated, restored the network toward the
      NOTCH1(+/+) state. Our results highlight how alterations in transcription factor
      dosage affect gene networks leading to human disease and reveal nodes for
      potential therapeutic intervention.

PMID- 25768905
TI  - Pumilio1 haploinsufficiency leads to SCA1-like neurodegeneration by increasing
      wild-type Ataxin1 levels.
AB  - Spinocerebellar ataxia type 1 (SCA1) is a paradigmatic neurodegenerative
      proteinopathy, in which a mutant protein (in this case, ATAXIN1) accumulates in
      neurons and exerts toxicity; in SCA1, this process causes progressive
      deterioration of motor coordination. Seeking to understand how post-translational
      modification of ATAXIN1 levels influences disease, we discovered that the RNA
      binding protein PUMILIO1 (PUM1) not only directly regulates ATAXIN1 but also
      plays an unexpectedly important role in neuronal function. Loss of Pum1 caused
      progressive motor dysfunction and SCA1-like neurodegeneration with motor
      impairment, primarily by increasing Ataxin1 levels. Breeding Pum1(+/-) mice to
      SCA1 mice (Atxn1(154Q/+)) exacerbated disease progression, whereas breeding them
      to Atxn1(+/-) mice normalized Ataxin1 levels and largely rescued the Pum1(+/-)
      phenotype. Thus, both increased wild-type ATAXIN1 levels and PUM1
      haploinsufficiency could contribute to human neurodegeneration. These results
      demonstrate the importance of studying post-transcriptional regulation of disease
      driving proteins to reveal factors underlying neurodegenerative disease.

PMID- 25768906
TI  - Hepatitis C virus RNA functionally sequesters miR-122.
AB  - Hepatitis C virus (HCV) uniquely requires the liver-specific microRNA-122 for
      replication, yet global effects on endogenous miRNA targets during infection are
      unexplored. Here, high-throughput sequencing and crosslinking immunoprecipitation
      (HITS-CLIP) experiments of human Argonaute (AGO) during HCV infection showed
      robust AGO binding on the HCV 5'UTR at known and predicted miR-122 sites. On the
      human transcriptome, we observed reduced AGO binding and functional mRNA de
      repression of miR-122 targets during virus infection. This miR-122 "sponge"
      effect was relieved and redirected to miR-15 targets by swapping the miRNA
      tropism of the virus. Single-cell expression data from reporters containing miR
      122 sites showed significant de-repression during HCV infection depending on
      expression level and site number. We describe a quantitative mathematical model
      of HCV-induced miR-122 sequestration and propose that such miR-122 inhibition by
      HCV RNA may result in global de-repression of host miR-122 targets, providing an
      environment fertile for the long-term oncogenic potential of HCV. 

PMID- 25768907
TI  - Codon optimality is a major determinant of mRNA stability.
AB  - mRNA degradation represents a critical regulated step in gene expression.
      Although the major pathways in turnover have been identified, accounting for
      disparate half-lives has been elusive. We show that codon optimality is one
      feature that contributes greatly to mRNA stability. Genome-wide RNA decay
      analysis revealed that stable mRNAs are enriched in codons designated optimal,
      whereas unstable mRNAs contain predominately non-optimal codons. Substitution of
      optimal codons with synonymous, non-optimal codons results in dramatic mRNA
      destabilization, whereas the converse substitution significantly increases
      stability. Further, we demonstrate that codon optimality impacts ribosome
      translocation, connecting the processes of translation elongation and decay
      through codon optimality. Finally, we show that optimal codon content accounts
      for the similar stabilities observed in mRNAs encoding proteins with coordinated
      physiological function. This work demonstrates that codon optimization exists as
      a mechanism to finely tune levels of mRNAs and, ultimately, proteins.

PMID- 25768908
TI  - The RNA binding protein quaking regulates formation of circRNAs.
AB  - Circular RNAs (circRNAs), formed by non-sequential back-splicing of pre-mRNA
      transcripts, are a widespread form of non-coding RNA in animal cells. However, it
      is unclear whether the majority of circRNAs represent splicing by-products
      without function or are produced in a regulated manner to carry out specific
      cellular functions. We show that hundreds of circRNAs are regulated during human
      epithelial-mesenchymal transition (EMT) and find that the production of over one
      third of abundant circRNAs is dynamically regulated by the alternative splicing
      factor, Quaking (QKI), which itself is regulated during EMT. Furthermore, by
      modulating QKI levels, we show the effect on circRNA abundance is dependent on
      intronic QKI binding motifs. Critically, the addition of QKI motifs is sufficient
      to induce de novo circRNA formation from transcripts that are normally linearly
      spliced. These findings demonstrate circRNAs are both purposefully synthesized
      and regulated by cell-type specific mechanisms, suggesting they play specific
      biological roles in EMT. 

PMID- 25768910
TI  - Chromatin fibers are formed by heterogeneous groups of nucleosomes in vivo.
AB  - Nucleosomes help structure chromosomes by compacting DNA into fibers. To gain
      insight into how nucleosomes are arranged in vivo, we combined quantitative super
      resolution nanoscopy with computer simulations to visualize and count nucleosomes
      along the chromatin fiber in single nuclei. Nucleosomes assembled in
      heterogeneous groups of varying sizes, here termed "clutches," and these were
      interspersed with nucleosome-depleted regions. The median number of nucleosomes
      inside clutches and their compaction defined as nucleosome density were cell-type
      specific. Ground-state pluripotent stem cells had, on average, less dense
      clutches containing fewer nucleosomes and clutch size strongly correlated with
      the pluripotency potential of induced pluripotent stem cells. RNA polymerase II
      preferentially associated with the smallest clutches while linker histone H1 and
      heterochromatin were enriched in the largest ones. Our results reveal how the
      chromatin fiber is formed at nanoscale level and link chromatin fiber
      architecture to stem cell state.

PMID- 25768909
TI  - Asymmetric unwrapping of nucleosomes under tension directed by DNA local
      flexibility.
AB  - Dynamics of the nucleosome and exposure of nucleosomal DNA play key roles in many
      nuclear processes, but local dynamics of the nucleosome and its modulation by DNA
      sequence are poorly understood. Using single-molecule assays, we observed that
      the nucleosome can unwrap asymmetrically and directionally under force. The
      relative DNA flexibility of the inner quarters of nucleosomal DNA controls the
      unwrapping direction such that the nucleosome unwraps from the stiffer side. If
      the DNA flexibility is similar on two sides, it stochastically unwraps from
      either side. The two ends of the nucleosome are orchestrated such that the
      opening of one end helps to stabilize the other end, providing a mechanism to
      amplify even small differences in flexibility to a large asymmetry in nucleosome
      stability. Our discovery of DNA flexibility as a critical factor for nucleosome
      dynamics and mechanical stability suggests a novel mechanism of gene regulation
      by DNA sequence and modifications. 

PMID- 25768912
TI  - Depth profiling charge accumulation from a ferroelectric into a doped Mott
      insulator.
AB  - The electric field control of functional properties is a crucial goal in oxide
      based electronics. Nonvolatile switching between different resistivity or
      magnetic states in an oxide channel can be achieved through charge accumulation
      or depletion from an adjacent ferroelectric. However, the way in which charge
      distributes near the interface between the ferroelectric and the oxide remains
      poorly known, which limits our understanding of such switching effects. Here, we
      use a first-of-a-kind combination of scanning transmission electron microscopy
      with electron energy loss spectroscopy, near-total-reflection hard X-ray
      photoemission spectroscopy, and ab initio theory to address this issue. We
      achieve a direct, quantitative, atomic-scale characterization of the polarization
      induced charge density changes at the interface between the ferroelectric BiFeO3
      and the doped Mott insulator Ca(1-x)Ce(x)MnO3, thus providing insight on how
      interface-engineering can enhance these switching effects.

PMID- 25768911
TI  - Compartmentalization of a bistable switch enables memory to cross a feedback
      driven transition.
AB  - Cells make accurate decisions in the face of molecular noise and environmental
      fluctuations by relying not only on present pathway activity, but also on their
      memory of past signaling dynamics. Once a decision is made, cellular transitions
      are often rapid and switch-like due to positive feedback loops in the regulatory
      network. While positive feedback loops are good at promoting switch-like
      transitions, they are not expected to retain information to inform subsequent
      decisions. However, this expectation is based on our current understanding of
      network motifs that accounts for temporal, but not spatial, dynamics. Here, we
      show how spatial organization of the feedback-driven yeast G1/S switch enables
      the transmission of memory of past pheromone exposure across this transition. We
      expect this to be one of many examples where the exquisite spatial organization
      of the eukaryotic cell enables previously well-characterized network motifs to
      perform new and unexpected signal processing functions. 

PMID- 25768913
TI  - EEG-based classification of video quality perception using steady state visual
      evoked potentials (SSVEPs).
AB  - OBJECTIVE: Recent studies exploit the neural signal recorded via
      electroencephalography (EEG) to get a more objective measurement of perceived
      video quality. Most of these studies capitalize on the event-related potential
      component P3. We follow an alternative approach to the measurement problem
      investigating steady state visual evoked potentials (SSVEPs) as EEG correlates of
      quality changes. Unlike the P3, SSVEPs are directly linked to the sensory
      processing of the stimuli and do not require long experimental sessions to get a
      sufficient signal-to-noise ratio. Furthermore, we investigate the correlation of
      the EEG-based measures with the outcome of the standard behavioral assessment.
      APPROACH: As stimulus material, we used six gray-level natural images in six
      levels of degradation that were created by coding the images with the HM10.0 test
      model of the high efficiency video coding (H.265/MPEG-HEVC) using six different
      compression rates. The degraded images were presented in rapid alternation with
      the original images. In this setting, the presence of SSVEPs is a neural marker
      that objectively indicates the neural processing of the quality changes that are
      induced by the video coding. We tested two different machine learning methods to
      classify such potentials based on the modulation of the brain rhythm and on time
      locked components, respectively. MAIN RESULTS: Results show high accuracies in
      classification of the neural signal over the threshold of the perception of the
      quality changes. Accuracies significantly correlate with the mean opinion scores
      given by the participants in the standardized degradation category rating quality
      assessment of the same group of images. SIGNIFICANCE: The results show that
      neural assessment of video quality based on SSVEPs is a viable complement of the
      behavioral one and a significantly fast alternative to methods based on the P3
      component.

PMID- 25768914
TI  - Genetically improved monolayer-forming tobacco mosaic viruses to generate
      nanostructured semiconducting bio/inorganic hybrids.
AB  - The genetically determined design of structured functional bio/inorganic
      materials was investigated by applying a convective assembly approach. Wildtype
      tobacco mosaic virus (wt TMV) as well as several TMV mutants were organized on
      substrates over macroscopic-length scales. Depending on the virus type, the self
      organization behavior showed pronounced differences in the surface arrangement
      under the same convective assembly conditions. Additionally, under varying
      assembly parameters, the virus particles generated structures encompassing
      morphologies emerging from single micrometer long fibers aligned parallel to the
      triple-contact line through disordered but dense films to smooth and uniform
      monolayers. Monolayers with diverse packing densities were used as templates to
      form TMV/ZnO hybrid materials. The semiconducting properties can be directly
      designed and tuned by the variation of the template architecture which are
      reflected in the transistor performance. 

PMID- 25768915
TI  - Effect of Apigenin on Leishmania amazonensis Is Associated with Reactive Oxygen
      Species Production Followed by Mitochondrial Dysfunction.
AB  - Leishmaniasis is an important neglected disease caused by protozoa of the genus
      Leishmania that affects more than 12 million people worldwide. Leishmaniasis
      treatment requires the administration of toxic and poorly tolerated drugs, and
      parasite resistance greatly reduces the efficacy of conventional medications.
      Apigenin (1), a naturally occurring plant flavone, has a wide range of reported
      biological effects. In this study, antileishmanial activity of 1 in vitro was
      investigated, and its mechanism of action against Leishmania amazonensis
      promastigotes was described. Treatment with 1 for 24 h resulted in concentration
      dependent inhibition of cellular proliferation (IC50 = 23.7 MUM) and increased
      reactive oxygen species (ROS) generation. Glutathione and N-acetyl-l-cysteine
      protected L. amazonensis from the effects of 1 and reduced ROS levels after the
      treatment. By contrast, oxidized glutathione did not reduce the levels of ROS
      caused by 1 by not preventing the proliferation inhibition. Apigenin 1 also
      induced an extensive swelling in parasite mitochondria, leading to an alteration
      of the mitochondrial membrane potential, rupture of the trans-Golgi network, and
      cytoplasmic vacuolization. These results demonstrate the leishmanicidal effect of
      1 and suggest the involvement of ROS leading to mitochondrial collapse as part of
      the mechanism of action. 

PMID- 25768916
TI  - Targeting the human androgen receptor gene with platinated triplex-forming
      oligonucleotides.
AB  - Platinum-derivatized homopyrimidine triplex-forming oligonucleotides (Pt-TFOs)
      consisting of 2'-O-methyl-5-methyluridine, 2'-O-methyl-5-methylcytidine, and a
      single 3'-N7-trans-chlorodiammine platinum(II)-2'-deoxyguanosine were designed to
      cross-link to the transcribed strand at four different sequences in the human
      androgen receptor (AR) gene. Fluorescence microscopy showed that a fluorescein
      tagged Pt-TFO localizes in both the cytoplasm and nucleus when it is transfected
      into LAPC-4 cells, a human prostate cancer cell line, using Lipofectamine 2000. A
      capture assay employing streptavidin-coated magnetic beads followed by polymerase
      chain reaction (PCR) amplification was used to demonstrate that 5'-biotin
      conjugated Pt-TFOs cross-link in vitro to their four designated AR gene targets
      in genomic DNA extracted from LAPC-4 cells. Similarly, the capture assay was used
      to examine cross-linking between the 5'-biotin-conjugated Pt-TFOs and the AR gene
      in LAPC-4 cells in culture. Three of the four Pt-TFOs cross-linked to their
      designated target, suggesting that different regions of the AR gene are not
      uniformly accessible to Pt-TFO cross-linking. LAPC-4 cells were transfected with
      fluorescein-tagged Pt-TFO or a control oligonucleotide that does not bind or
      cross-link to AR DNA. The levels of AR mRNA in highly fluorescent cells isolated
      by fluorescence-activated cell sorting were determined by RT-qPCR, and the levels
      of AR protein were monitored by immunofluorescence microscopy. Decreases in mRNA
      and protein levels of 40 and 30%, respectively, were observed for fluorescein
      tagged Pt-TFO versus control treated cells. Although the levels of knockdown of
      AR mRNA and protein were modest, the results suggest that Pt-TFOs hold potential
      as agents for controlling gene expression by cross-linking to DNA and disrupting
      transcription. 

PMID- 25768917
TI  - Total synthesis of the leucosceptroid family of natural products.
AB  - A highly efficient strategy enabled the asymmetric total synthesis of 15
      antifeedant leucosceptroid natural products. The advanced tricyclic core,
      available in gram quantity, served as the pivotal intermediate for the
      preparation of norleucosceptroids B, C, F, and G and leucosceptroids A, B, G, I,
      J, L, and M. Additionally, the bioinspired oxidative transformation of
      leucosceptroid A to leucosceptroids C, K, O, and P using singlet oxygen supports
      the hypothesis that leucosceptroids A and B are most likely the biogenetic
      precursors of all other members of this natural product family. 

PMID- 25768918
TI  - Effect of temperature on biochemical composition, growth and reproduction of the
      ornamental red cherry shrimp Neocaridina heteropoda heteropoda (Decapoda,
      Caridea).
AB  - The effect of water temperature on biochemical composition, growth and
      reproduction of the ornamental shrimp, Neocaridina heteropoda heteropoda, was
      investigated to determine the optimum temperature for its culture. The effect of
      embryo incubation temperature on the subsequent performance of juveniles was also
      evaluated. Ovigerous females and recently hatched juveniles (JI) were maintained
      during egg incubation and for a 90-day period, respectively, at three
      temperatures (24, 28 and 32  degrees C). Incubation period increased with
      decreasing water temperature, but the number and size of JI were similar among
      treatments. At day 30 of the 90-day period, body weight and growth increment (GI)
      at 24  degrees C were lower than those at 28 and 32  degrees C. On subsequent
      days, GI at 24  degrees C exceeded that at 28 and 32  degrees C, leading to a
      similar body weight among treatments. These results suggest growth was delayed at
      24  degrees C, but only for 30 days after hatching. The lipid concentration
      tended to be lowest, intermediate and highest at 28, 32 and 24  degrees C,
      respectively, possibly as a consequence of the metabolic processes involved in
      growth and ovarian maturation. Protein and glycogen concentrations were similar
      among treatments. Both the growth trajectory and biochemical composition of
      shrimps were affected by the temperature experienced during the 90-day growth
      period independently of the embryo incubation temperature. During the growth
      period, shrimps reached sexual maturity and mated, with the highest proportion of
      ovigerous females occurring at 28  degrees C. All the females that matured and
      mated at 32  degrees C lost their eggs, indicating a potentially stressful effect
      of high temperature on ovarian maturation. Based on high survival and good growth
      performance of shrimps at the three temperatures tested over the 90-day period it
      is concluded that N. heteropoda heteropoda is tolerant to a wide range of water
      temperatures, with 28  degrees C being the optimum temperature for its culture.

PMID- 25768919
TI  - Residential exposure to traffic noise and health-related quality of life--a
      population-based study.
AB  - BACKGROUND: Few studies have investigated the association between objectively
      measured traffic noise and health-related quality of life. However, as traffic
      noise has been associated with both cardiovascular disease and diabetes, and
      health-issues including sleeping problems, annoyance, and stress, it seems
      plausible that traffic noise is associated with health-related quality of life.
      METHODS: Between 1999 and 2002, a cohort of 38,964 Danes filled in the short form
      36 (SF-36) questionnaire. Residential exposure to road traffic and railway noise
      was calculated for all historical addresses for 10 years preceding the SF-36,
      using the Nordic prediction method. Associations between noise exposure and SF-36
      summary scales and the eight sub-scales were calculated using general linear
      models, adjusted for age, sex, socioeconomic status, and lifestyle. RESULTS:
      Models adjusted for age, sex and socioeconomic factors showed that a 10 dB higher
      road traffic noise 1 year preceding SF-36 assessment was associated with a 0.14
      lower mental component summary (MCS) score (95% confidence interval (CI) -0.26, 
      0.01). However, further adjustment for lifestyle factors (smoking, alcohol, and
      waist circumference) attenuated the association: (-0.08 (95% CI: -0.20, 0.04)).
      Exposure to more than 55 dB of railway noise in the same time period was
      borderline significantly associated with lower MCS. The physical component
      summary was not associated with traffic noise. CONCLUSION: The present study
      suggests a weak association between traffic noise exposure and the mental health
      component score of SF-36, which may operate through lifestyle. The magnitude of
      effect was, however, not clinically relevant.

PMID- 25768920
TI  - Mitotic-chromosome-based physical mapping of the Culex quinquefasciatus genome.
AB  - The genome assembly of southern house mosquito Cx. quinquefasciatus is
      represented by a high number of supercontigs with no order or orientation on the
      chromosomes. Although cytogenetic maps for the polytene chromosomes of this
      mosquito have been developed, their utilization for the genome mapping remains
      difficult because of the low number of high-quality spreads in chromosome
      preparations. Therefore, a simple and robust mitotic-chromosome-based approach
      for the genome mapping of Cx. quinquefasciatus still needs to be developed. In
      this study, we performed physical mapping of 37 genomic supercontigs using
      fluorescent in situ hybridization on mitotic chromosomes from imaginal discs of
      4th instar larvae. The genetic linkage map nomenclature was adopted for the
      chromosome numbering based on the direct positioning of 58 markers that were
      previously genetically mapped. The smallest, largest, and intermediate
      chromosomes were numbered as 1, 2, and 3, respectively. For idiogram development,
      we analyzed and described in detail the morphology and proportions of the mitotic
      chromosomes. Chromosomes were subdivided into 19 divisions and 72 bands of four
      different intensities. These idiograms were used for mapping the genomic
      supercontigs/genetic markers. We also determined the presence of length
      polymorphism in the q arm of sex-determining chromosome 1 in Cx. quinquefasciatus
      related to the size of ribosomal locus. Our physical mapping and previous genetic
      linkage mapping resulted in the chromosomal assignment of 13% of the total genome
      assembly to the chromosome bands. We provided the first detailed description,
      nomenclature, and idiograms for the mitotic chromosomes of Cx. quinquefasciatus.
      Further application of the approach developed in this study will help to improve
      the quality of the southern house mosquito genome. 

PMID- 25768921
TI  - Early complications following oesophagectomy for cancer in relation to long-term
      healthcare utilisation: a prospective population-based cohort study.
AB  - BACKGROUND: Little is known about how early postoperative complications after
      oesophagectomy for cancer influence healthcare utilisation in the long-term. We
      hypothesised that these complications also increase healthcare utilisation long
      after the recovery period. METHODS: This was a prospective, nationwide Swedish
      population-based cohort study of patients who underwent curatively intended
      oesophagectomy for cancer in 2001-2005 and survived at least 1 year
      postoperatively (n = 390). Total days of in-hospitalisation, number of
      hospitalisations and number of visits to the outpatient clinic within 5 years of
      surgery were analysed using quasi-Poisson models with adjustment for patient,
      tumour and treatment characteristics and are expressed as incidence rate ratios
      (IRR) and 95% confidence intervals (CI). RESULTS: There was an increased in
      hospitalisation period 1-5 years after surgery in patients with more than 1
      complication (IRR 1.5, 95% CI 1.0-2.4). The IRR for the number of
      hospitalisations by number of complications was 1.1 (95% CI 0.7-1.6), and 1.2
      (95% CI 0.9-1.6) for number of outpatient visits in patients with more than 1
      complication. The IRR for in-hospitalisation period 1-5 years following
      oesophagectomy was 1.8 (95% CI 1.0-3.0) for patients with anastomotic
      insufficiency and 1.5 (95% CI 0.9-2.5) for patients with cardiovascular or
      cerebrovascular complications. We found no association with number of
      hospitalisations (IRR 1.2, 95% CI 0.7-2.0) or number of outpatient visits (IRR
      1.3, 95% CI 0.9-1.7) after anastomotic insufficiency, or after cardiovascular or
      cerebrovascular complications (IRR 1.2, 95% CI 0.7-1.9) and (IRR 1.1, 95% CI 0.8
      1.5) respectively. CONCLUSION: This study showed an increased total in
      hospitalisation period 1-5 years after oesophagectomy for cancer in patients with
      postoperative complications, particularly following anastomotic insufficiency.

PMID- 25768923
TI  - Correction: effects of climate variability and accelerated forest thinning on
      watershed-scale runoff in southwestern USA ponderosa pine forests.

PMID- 25768922
TI  - Mitochondrial reactive oxygen species regulate adipocyte differentiation of
      mesenchymal stem cells in hematopoietic stress induced by arabinosylcytosine.
AB  - OBJECTIVE: The increase in adipocytes induced by chemotherapeutic drugs may play
      a negative role in hematopoietic recovery. However, the mechanism underlying
      adipocyte differentiation of mesenchymal stem cells (MSCs) in hematopoietic
      stress is still unknown. Hence, the involvement of reactive oxygen species (ROS)
      in adipocyte differentiation under hematopoietic stress was investigated in vitro
      and in vivo. METHODS: The roles of cellular ROS in adipogenesis were investigated
      in vivo through an adipocyte hyperplasia marrow model under hematopoietic stress
      induced by arabinosylcytosine (Ara-C) and in vitro via adipocyte differentiation
      of human MSCs. ROS levels were detected using the CM-H2DCFDA probe and Mito-SOX
      dye. Adipogenesis was evaluated by histopathology and oil red O staining, whereas
      detection of mRNA levels of antioxidant enzymes and adipogenesis markers was
      performed using quantitative real-time polymerase chain reaction analysis.
      RESULTS: ROS were found to play an important role in regulating adipocyte
      differentiation of MSCs by activating peroxisome proliferator-activated receptor
      gamma (PPARgamma,) while the antioxidant N-acetyl-L-cysteine acts through ROS to
      inhibit adipocyte differentiation. The elevated ROS levels induced by Ara-C were
      caused by both over-generation of mitochondrial ROS and reduction of antioxidant
      enzymes (Cu/Zn Superoxide dismutase and catalase). Our findings suggest that a
      mitochondrial-targeted antioxidant could diminish adipocyte differentiation.

PMID- 25768924
TI  - Chronic HIV Infection Is Associated with Upregulation of Proinflammatory Cytokine
      and Chemokine and Alpha Defensin Gene Expression in Colorectal Mucosa.
AB  - HIV may induce gastrointestinal (GI) mucosal immune dysregulation similar to
      inflammation observed in ulcerative colitis (UC). Colorectal biopsies from
      healthy controls (N=12) and from participants with HIV (N=20) or UC (N=9) were
      subjected to real time (RT)-PCR for selected cytokines, chemokines, antimicrobial
      peptides, Toll-like receptors, and inflammatory signaling and epithelial barrier
      proteins. HIV long terminal repeat relative copy number (RCN) in HIV participant
      biopsies was quantified by RT-PCR. Mean interleukin (IL)-6 mRNA levels did not
      differ significantly between HIV and UC participants (p=0.48) but were
      significantly higher relative to control mRNA levels only for HIV participants
      (p=0.03). Mean IL-8 and human defensin (HD) 5 mRNA levels were similar between
      HIV and UC participants (p=1.0 and p=0.35, respectively) and were significantly
      greater in both groups relative to controls (p<0.05 for all). Human beta-defensin
      (HBD)-2 mRNA levels were higher in UC relative to HIV and control participants
      (p<0.01 for both). Conversely, HBD-1 mRNA levels were downregulated in UC vs. HIV
      participants (p=0.01). Mediator gene expression did not differ significantly
      between HIV participants with detectable (N=10) or nondetectable (N=10) plasma
      viral loads. Tissue HIV relative copy number (RCN) correlated with plasma viral
      load (r=0.88, p<0.01) but not with mediator mRNA levels. The results of this
      study indicate that both chronic HIV infection and UC are associated with similar
      patterns of IL-6, IL- 8, and HD5 expression in colorectal biopsy tissue. These
      findings suggest overlapping mechanisms for GI mucosal inflammation in these two
      illnesses and merit further investigation in larger studies. 

PMID- 25768925
TI  - Use of surveillance data on HIV diagnoses with HIV-related symptoms to estimate
      the number of people living with undiagnosed HIV in need of antiretroviral
      therapy.
AB  - BACKGROUND: It is important to have methods available to estimate the number of
      people who have undiagnosed HIV and are in need of antiretroviral therapy (ART).
      METHODS: The method uses the concept that a predictable level of occurrence of
      AIDS or other HIV-related clinical symptoms which lead to presentation for care,
      and hence diagnosis of HIV, arises in undiagnosed people with a given CD4 count.
      The method requires surveillance data on numbers of new HIV diagnoses with HIV
      related symptoms, and the CD4 count at diagnosis. The CD4 count-specific rate at
      which HIV-related symptoms develop are estimated from cohort data. 95% confidence
      intervals can be constructed using a simple simulation method. RESULTS: For
      example, if there were 13 HIV diagnoses with HIV-related symptoms made in one
      year with CD4 count at diagnosis between 150-199 cells/mm3, then since the CD4
      count-specific rate of HIV-related symptoms is estimated as 0.216 per person
      year, the estimated number of person years lived in people with undiagnosed HIV
      with CD4 count 150-199 cells/mm3 is 13/0.216 = 60 (95% confidence interval: 29
      100), which is considered an estimate of the number of people living with
      undiagnosed HIV in this CD4 count stratum. CONCLUSIONS: The method is
      straightforward to implement within a short period once a surveillance system of
      all new HIV diagnoses, collecting data on HIV-related symptoms at diagnosis, is
      in place and is most suitable for estimating the number of undiagnosed people
      with CD4 count <200 cells/mm3 due to the low rate of developing HIV-related
      symptoms at higher CD4 counts. A potential source of bias is under-diagnosis and
      under-reporting of diagnoses with HIV-related symptoms. Although this method has
      limitations as with all approaches, it is important for prompting increased
      efforts to identify undiagnosed people, particularly those with low CD4 count,
      and for informing levels of unmet need for ART.

PMID- 25768926
TI  - Age-Related Changes in Cognitive and Sensory Processing: Focus on Middle-Aged
      Adults.
AB  - PURPOSE: The purpose of this article was to examine the effects of age on (a)
      various psychophysical measures of threshold sensitivity and temporal processing
      in hearing, vision, and touch and (b) measures of cognitive processing as
      assessed by the Wechsler Adult Intelligence Scale-Third Edition (Wechsler, 1997).
      METHOD: Age group differences and correlations with age were examined, as were
      associations among age, sensory processing, and cognition. RESULTS: The group
      analyses showed significant differences on most sensory and cognitive measures
      such that middle-aged adults performed significantly worse than young adults and
      significantly better than older adults. Correlations of performance with age were
      also significant when analyses were restricted to just the young and middle-aged
      adults. Last, sensory processing, but not age, was significantly correlated with
      cognitive processing when analyses were restricted to just the young and middle
      aged adults. CONCLUSION: Middle-aged adults experienced declines in both sensory
      and cognitive processing. The declines in both the cognitive and sensory domains
      were such that, for most measures in each domain, the performance of middle-aged
      adults fell somewhere between that of young and older adults.

PMID- 25768927
TI  - A convenient and quantitative route to Sn(IV)-M [M = Ti(IV), Nb(V), Ta(V)]
      heterobimetallic precursors for dense mixed-metal oxide ceramics.
AB  - The strategy of reacting SnCl4 with M(OR)x provided a convenient and quantitative
      approach to new heterobimetallics with a simple addition formula,
      [SnCl4M(OR)x(HOR)y] (M = Ti, Nb, Ta; R = Et, Pr(i), x = 4, 5; y = 0-2) or
      sometimes an oxo complex [SnCl3(O)Ti2(OPr(i))7(HOPr(i))2]. The alcoholysis
      reactions of these heterometallics afforded mixed alkoxo complexes [SnCl4(MU
      OEt)2M(Pr(i)O)x(Pr(i)OH)y] [M = Ti (x = y = 2), Nb, Ta (x = 3, y = 1)] under mild
      conditions, or a planar rectangular oxo product [SnCl3(MU-OEt)2Nb(OEt)2(EtOH)(MU
      O)]2 at refluxing/extended stirring time. DFT calculations shed light on the
      stability and reactivity of these complexes. The use of these thoroughly
      characterized heterometallics as sol-gel precursors suppresses the formation of
      the undesired SnO2 grains, which are difficult to be sintered to a high density.
      The combined approach of using bottom-up synthesis of mixed Ti0.5Sn0.5O2
      nanoparticles and Spark Plasma Sintering allowed the successful densification of
      chloride-free mixed-metal oxide ceramics. The influence of thermal treatment
      before sintering on the density and spinodal decomposition of the TiO2-SnO2
      pellets is reported. 

PMID- 25768928
TI  - Pleiotropy among common genetic loci identified for cardiometabolic disorders and
      C-reactive protein.
AB  - Pleiotropic genetic variants have independent effects on different phenotypes. C
      reactive protein (CRP) is associated with several cardiometabolic phenotypes.
      Shared genetic backgrounds may partially underlie these associations. We
      conducted a genome-wide analysis to identify the shared genetic background of
      inflammation and cardiometabolic phenotypes using published genome-wide
      association studies (GWAS). We also evaluated whether the pleiotropic effects of
      such loci were biological or mediated in nature. First, we examined whether 283
      common variants identified for 10 cardiometabolic phenotypes in GWAS are
      associated with CRP level. Second, we tested whether 18 variants identified for
      serum CRP are associated with 10 cardiometabolic phenotypes. We used a Bonferroni
      corrected p-value of 1.1*10-04 (0.05/463) as a threshold of significance. We
      evaluated the independent pleiotropic effect on both phenotypes using individual
      level data from the Women Genome Health Study. Evaluating the genetic overlap
      between inflammation and cardiometabolic phenotypes, we found 13 pleiotropic
      regions. Additional analyses showed that 6 regions (APOC1, HNF1A, IL6R, PPP1R3B,
      HNF4A and IL1F10) appeared to have a pleiotropic effect on CRP independent of the
      effects on the cardiometabolic phenotypes. These included loci where individuals
      carrying the risk allele for CRP encounter higher lipid levels and risk of type 2
      diabetes. In addition, 5 regions (GCKR, PABPC4, BCL7B, FTO and TMEM18) had an
      effect on CRP largely mediated through the cardiometabolic phenotypes. In
      conclusion, our results show genetic pleiotropy among inflammation and
      cardiometabolic phenotypes. In addition to reverse causation, our data suggests
      that pleiotropic genetic variants partially underlie the association between CRP
      and cardiometabolic phenotypes. 

PMID- 25768930
TI  - Rh(III)-catalyzed oxidative annulation of 2-phenylimidazo[1,2-a]pyridines with
      alkynes: mono versus double C-H activation.
AB  - Rh(III)-catalyzed C-H activation of 2-phenylimidazo[1,2-a]pyridines in divergent
      oxidative coupling with alkynes has been achieved. Selective mono versus 2-fold C
      H activation has been attained under condition control. When AgOAc was used as an
      oxidant, the coupling afforded 5,6-disubstituted naphtho[1',2':4,5]imidazo[1,2
      a]pyridines as a result of initial nitrogen chelation-assisted C-H activation at
      the benzene ring followed by rollover C-H activation. In contrast, the reaction
      afforded a fused isoquinolinium salt as a result of C-C and C-N coupling when
      AgBF4 was employed as a co-oxidant. A rhodacyclic intermediate has been isolated.

PMID- 25768929
TI  - Egg-in-cube: design and fabrication of a novel artificial eggshell with
      functionalized surface.
AB  - An eggshell is a porous microstructure that regulates the passage of gases to
      allow respiration. The chick embryo and its circulatory system enclosed by the
      eggshell has become an important model for biomedical research such as the
      control of angiogenesis, cancer therapy, and drug delivery test, because the use
      of embryo is ethically acceptable and it is inexpensive and small. However, chick
      embryo and extra-embryonic blood vessels cannot be accessed freely and has poor
      observability because the eggshell is tough and cannot be seen through, which
      limits its application. In this study, a novel artificial eggshell with
      functionalized surface is proposed, which allows the total amount of oxygen to
      pass into the egg for the chick embryo culturing and has high observability and
      accessibility for embryo manipulation. First, a 40-mm enclosed cubic-shaped
      eggshell consisting of a membrane structure and a rigid frame structure is
      designed, and then the threshold of the membrane thickness suitable for the
      embryo survival is figured out according to the oxygen-permeability of the
      membrane structure. The designed artificial eggshell was actually fabricated by
      using polydimethylsiloxane (PDMS) and polycarbonate (PC) in the current study.
      Using the fabricated eggshell, chick embryo and extra-embryonic blood vessels can
      be observed from multiple directions. To test the effectiveness of the design,
      the cubic eggshells were used to culture chick embryos and survivability was
      confirmed when PDMS membranes with adequate oxygen permeability were used. Since
      the surface of the eggshell is transparent, chick embryo tissue development could
      be observed during the culture period. Additionally, the chick embryo tissues
      could be accessed and manipulated from outside the cubic eggshell, by using
      mechanical tools without breakage of the eggshell. The proposed "Egg-in-Cube"
      with functionalized surface has great potential to serve as a promising platform
      for biomedical research. 

PMID- 25768931
TI  - Ultrafast and low temperature synthesis of highly crystalline and patternable few
      layers tungsten diselenide by laser irradiation assisted selenization process.
AB  - Recently, a few attempts to synthesize monolayers of transition metal
      dichalcogenides (TMDs) using the chemical vapor deposition (CVD) process had been
      demonstrated. However, the development of alternative processes to synthesize
      TMDs is an important step because of the time-consuming, required transfer and
      low thermal efficiency of the CVD process. Here, we demonstrate a method to
      achieve few-layers WSe2 on an insulator via laser irradiation assisted
      selenization (LIAS) process directly, for which the amorphous WO3 film undergoes
      a reduction process in the presence of selenium gaseous vapors to form WSe2,
      utilizing laser annealing as a heating source. Detailed growth parameters such as
      laser power and laser irradiation time were investigated. In addition,
      microstructures, optical and electrical properties were investigated.
      Furthermore, a patternable WSe2 concept was demonstrated by patterning the WO3
      film followed by the laser irradiation. By combining the patternable process, the
      transfer-free WSe2 back gate field effect transistor (FET) devices are realized
      on 300 nm-thick SiO2/P(+)Si substrate with extracted field effect mobility of
      ~0.2 cm(2) V(-1) s(-1). Similarly, the reduction process by the laser irradiation
      can be also applied for the synthesis of other TMDs such as MoSe2 from other
      metal oxides such as MO3 film, suggesting that the process can be further
      extended to other TMDs. The method ensures one-step process to fabricate
      patternable TMDs, highlighting the uniqueness of the laser irradiation for the
      synthesis of different TMDs. 

PMID- 25768932
TI  - p38 MAPK signaling in postnatal tendon growth and remodeling.
AB  - Tendon is a dynamic tissue whose structure and function is influenced by
      mechanical loading, but little is known about the fundamental mechanisms that
      regulate tendon growth and remodeling in vivo. Data from cultured tendon
      fibroblasts indicated that the p38 MAPK pathway plays an important role in tendon
      fibroblast proliferation and collagen synthesis in vitro. To gain greater insight
      into the mechanisms of tendon growth, and explore the role of p38 MAPK signaling
      in this process, we tested the hypotheses that inducing plantaris tendon growth
      through the ablation of the synergist Achilles tendon would result in rapid
      expansion of a neotendon matrix surrounding the original tendon, and that
      treatment with the p38 MAPK inhibitor SB203580 would prevent this growth. Rats
      were treated with vehicle or SB203580, and subjected to synergist ablation by
      bilateral tenectomy of the Achilles tendon. Changes in histological and
      biochemical properties of plantaris tendons were analyzed 3, 7, or 28 days after
      overload, and comparisons were made to non-overloaded animals. By 28 days after
      overload, tendon mass had increased by 30% compared to non-overloaded samples,
      and cross-sectional area (CSA) increased by around 50%, with most of the change
      occurring in the neotendon. The expansion in CSA initially occurred through the
      synthesis of a hyaluronic acid rich matrix that was progressively replaced with
      mature collagen. Pericytes were present in areas of active tendon growth, but
      never in the original tendon ECM. Inhibition of p38 MAPK resulted in a profound
      decrease in IL6 expression, and had a modest effect on the expression of other
      ECM and cell proliferation genes, but had a negligible impact on overall tendon
      growth. The combined results from this study provided novel insights into tendon
      mechanobiology, and suggest that p38 MAPK signaling does not appear to be
      necessary for tendon growth in vivo. 

PMID- 25768934
TI  - Enhanced photoelectrocatalytic decomposition of copper cyanide complexes and
      simultaneous recovery of copper with a Bi2MoO6 electrode under visible light by
      EDTA/K4P2O7.
AB  - Simultaneous photoelectrocatalytic (PEC) oxidation of cyanides and recovery of
      copper in a PEC reactor with a Bi(2)MoO(6) photoanode was investigated at
      alkaline conditions under visible light irradiation. The surface variation of the
      Bi(2)MoO(6) photoanode and titanium cathode was characterized. The Cu mass
      distribution onto the anode, in the solution, and onto the cathode was fully
      investigated. In the individual PEC oxidation of copper cyanides, the formation
      of a black copper oxide on the anode occurred. By keeping the initial cyanide
      concentration at 0.01 mM, the effect of EDTA/K(4)P(2)O(7) was examined at
      different molar ratios of EDTA/K(4)P(2)O(7) to cyanide. It was indicated that the
      oxidation of cyanides increased and simultaneous copper electrodeposition with
      zero value onto the cathode was feasible at pH 11. Under the optimal conditions,
      the total cyanide concentration was lowered from 250 to 5.0 mg/L, and the Cu
      recovery efficiency deposited onto the cathode was higher than 90%. Cyanate was
      the only product. The role of the photogenerated hole in the oxidation of cyanide
      ions was confirmed.

PMID- 25768933
TI  - Flexible bronchoscopy with multiple modalities for foreign body removal in
      adults.
AB  - OBJECTIVES: Aspiration of the lower airways due to foreign body is rare in
      adults. This study aimed to determine the outcome of patients who received
      flexible bronchoscopy with different modalities for foreign body removal in the
      lower airways. PATIENTS AND METHODS: Between January 2003 and January 2014, 94
      patients diagnosed with foreign body in the lower airways underwent flexible
      bronchoscopy with different modalities, which included forceps, loop, basket,
      knife, electromagnet, and cryotherapy. The clinical presentation, foreign body
      location and characteristics, and applications of flexible bronchoscopy were
      analyzed. RESULTS: Forty (43%) patients had acute aspiration, which developed
      within one week of foreign body entry and 54 (57%) had chronic aspiration. The
      most common foreign bodies were teeth or bone. More patients with chronic
      aspiration than those with acute aspiration were referred from the out-patient
      clinic (48% vs. 28%), but more patients with acute aspiration were referred from
      the emergency room (35% vs. 6%) and intensive care unit (18% vs. 2%). Flexible
      bronchoscopy with different modalities was used to remove the foreign bodies
      (85/94, 90%). Electromagnet or cryotherapy was used in nine patients to eliminate
      the surrounding granulation tissue before foreign body removal. In the nine
      patients with failed flexible bronchoscopy, eight underwent rigid bronchoscopy
      instead and one had right lower lung lobectomy for lung abscess. CONCLUSIONS:
      Flexible bronchoscopy with multiple modalities is effective for diagnosing and
      removing foreign bodies in the lower respiratory airways in adults, with a high
      success rate (90%) and no difference between acute and chronic aspirations.

PMID- 25768935
TI  - Pharmacological interventions for pain in children and adolescents with life
      limiting conditions.
AB  - BACKGROUND: Pain is one of the most common symptoms in children and young people
      (CYP) with life-limiting conditions (LLCs) which include a wide range of
      diagnoses including cancer. The current literature indicates that pain is not
      well managed, however the evidence base to guide clinicians is limited. There is
      a clear need for evidence from a systematic review to inform prescribing.
      OBJECTIVES: To evaluate the evidence on the effectiveness of different
      pharmacological interventions used for pain in CYP with LLCs. SEARCH METHODS: The
      following electronic databases were searched up to December 2014: CENTRAL (in the
      Cochrane Library), MEDLINE, EMBASE, PsycINFO and CINAHL. In addition, we searched
      conference proceedings and reference lists of included studies. For completeness,
      we also contacted experts in the field. No language restrictions were applied.
      SELECTION CRITERIA: Randomised controlled trials (RCTs), quasi-randomised studies
      and other studies that included a clearly defined comparator group were included.
      The studies investigated pharmacological treatments for pain associated with LLCs
      in CYP. The treatment included those specifically developed to treat pain and
      those that acted as an adjuvant, where the treatment was not primarily developed
      to treat pain but has pain relieving properties. The LLC was identified by its
      inclusion in the Richard Hain Directory of LLCs. DATA COLLECTION AND ANALYSIS:
      Citations were screened by five review authors. Data were extracted by one review
      author and checked by a second. Two review authors assessed the risk of bias of
      included studies. A sufficient number of studies using homogeneous outcomes was
      not identified so a meta-analysis was not possible. MAIN RESULTS: We identified
      24,704 citations from our database search. Nine trials with 379 participants
      fulfilled our inclusion criteria. Participants had cerebral palsy (CP) in five of
      the studies and osteogenesis imperfecta (OI) in the other four. Participants
      across the trials ranged in age from 2 to 19 years. All studies, apart from one
      cross-over trial, were parallel designed RCTs. Three of the trials on CP
      evaluated intrathecal baclofen (ITB) and two botulinum toxin A (BoNT-A). All of
      the OI trials evaluated the use of bisphosphonates (two alendronate and one
      pamidronate). No trials were identified that evaluated a commonly used analgesic
      in this patient group. Pain was a secondary outcome in five of the eight
      identified studies. Overall the quality of the trials was mixed. Only one study
      involved over 100 participants.For the two ITB studies for pain in CP, in the
      same study population but assessed at different time points in their disease,
      both found an effect on pain favouring the intervention compared to the control
      group (standard care or placebo) (mean difference (MD) 4.20, 95% confidence
      interval (CI) 2.15 to 6.25; MD 26.60, 95% CI 2.61 to 50.59, respectively). In
      these studies most of the adverse events related to the procedure or device for
      administration rather than the drug, such as swelling at the pump site. In one
      trial there were also eight serious adverse effects; these included difficulty
      swallowing and an epileptic seizure. The trial did not state if these occurred in
      the intervention group. At follow-up in both BoNT-A trials there was no evidence
      of a difference in pain between the trial arms among CP participants. The adverse
      events in the BoNT-A trials mostly involved those who received the intervention
      drug and involved seizures. Gastrointestinal problems were the most frequent
      adverse event in those who received alendronate. The trial investigating
      pamidronate found no evidence of a difference in pain compared to the control
      group. No adverse events were reported in this trial. AUTHORS' CONCLUSIONS:
      Published, controlled evidence on the pharmacological interventions for pain in
      CYP with LLCs is limited. The evidence that is currently available evaluated pain
      largely as a secondary outcome and the drugs used were all adjuvants and not
      always commonly used in general paediatric palliative care for pain. Based on
      current data this systematic review is unable to determine the effects of
      pharmacological interventions for pain for CYP with LLCs. Future trials with
      larger populations should examine the effects of the drugs commonly used as
      analgesics; with the rising prevalence of many LLCs this becomes more necessary.

PMID- 25768755
TI  - Search for Higgs boson pair production in the gammagammabb[over -] final state
      using pp collision data at sqrt[s]=8  TeV from the ATLAS detector.
AB  - Searches are performed for resonant and nonresonant Higgs boson pair production
      in the gammagammabb[over -] final state using 20  fb^{-1} of proton-proton
      collisions at a center-of-mass energy of 8 TeV recorded with the ATLAS detector
      at the CERN Large Hadron Collider. A 95% confidence level upper limit on the
      cross section times branching ratio of nonresonant production is set at 2.2 pb,
      while the expected limit is 1.0 pb. The difference derives from a modest excess
      of events, corresponding to 2.4 standard deviations from the background-only
      hypothesis. The limit observed in the search for a narrow X->hh resonance ranges
      between 0.7 and 3.5 pb as a function of the resonance mass. 

PMID- 25768936
TI  - High soluble endoglin levels do not induce endothelial dysfunction in mouse
      aorta.
AB  - Increased levels of a soluble form of endoglin (sEng) circulating in plasma have
      been detected in various pathological conditions related to cardiovascular
      system. High concentration of sEng was also proposed to contribute to the
      development of endothelial dysfunction, but there is no direct evidence to
      support this hypothesis. Therefore, in the present work we analyzed whether high
      sEng levels induce endothelial dysfunction in aorta by using transgenic mice with
      high expression of human sEng. Transgenic mice with high expression of human sEng
      on CBAxC57Bl/6J background (Sol-Eng+) and age-matched transgenic littermates that
      do not develop high levels of human soluble endoglin (control animals in this
      study) on chow diet were used. As expected, male and female Sol-Eng+ transgenic
      mice showed higher levels of plasma concentrations of human sEng as well as
      increased blood arterial pressure, as compared to control animals. Functional
      analysis either in vivo or ex vivo in isolated aorta demonstrated that the
      endothelium-dependent vascular function was similar in Sol-Eng+ and control mice.
      In addition, Western blot analysis showed no differences between Sol-Eng+ and
      control mice in the protein expression levels of endoglin, endothelial NO
      synthase (eNOS) and pro-inflammatory ICAM-1 and VCAM-1 from aorta. Our results
      demonstrate that high levels of soluble endoglin alone do not induce endothelial
      dysfunction in Sol-Eng+ mice. However, these data do not rule out the possibility
      that soluble endoglin might contribute to alteration of endothelial function in
      combination with other risk factors related to cardiovascular disorders. 

PMID- 25768938
TI  - Characterization of CD8+ T cell differentiation following SIVDeltanef vaccination
      by transcription factor expression profiling.
AB  - The onset of protective immunity against pathogenic SIV challenge in SIVDeltanef
      vaccinated macaques is delayed for 15-20 weeks, a process that is related to
      qualitative changes in CD8+ T cell responses induced by SIVDeltanef. As a novel
      approach to characterize cell differentiation following vaccination, we used
      multi-target qPCR to measure transcription factor expression in naive and memory
      subsets of CD8++ T cells, and in SIV-specific CD8+ T cells obtained from
      SIVDeltanef-vaccinated or wild type SIVmac239-infected macaques. Unsupervised
      clustering of expression profiles organized naive and memory CD8+ T cells into
      groups concordant with cell surface phenotype. Transcription factor expression
      patterns in SIV-specific CD8+ T cells in SIVDeltanef-vaccinated animals were
      distinct from those observed in purified CD8+ T cell subsets obtained from naive
      animals, and were intermediate to expression profiles of purified central memory
      and effector memory T cells. Expression of transcription factors elicited by
      SIVDeltanef vaccination also varied over time: cells obtained at later time
      points, temporally associated with greater protection, appeared more central
      memory like than cells obtained at earlier time points, which appeared more
      effector memory-like. Expression of transcription factors associated with
      effector differentiation, such as ID2 and RUNX3, were decreased over time, while
      expression of transcription factors associated with quiescence or memory
      differentiation, such as TCF7, BCOR and EOMES, increased. CD8+ T cells specific
      for a more conserved epitope expressed higher levels of TBX21 and BATF, and
      appeared more effector-like than cells specific for an escaped epitope,
      consistent with continued activation by replicating vaccine virus. These data
      suggest transcription factor expression profiling is a novel method that can
      provide additional data complementary to the analysis of memory cell
      differentiation based on classical phenotypic markers. Additionally, these data
      support the hypothesis that ongoing stimulation by SIVDeltanef promotes a
      distinct protective balance of CD8+ T cell differentiation and activation states.

PMID- 25768939
TI  - "What Is eHealth": Time for An Update?
AB  - The annual number of articles reporting on eHealth interventions has increased
      over the last 10 years. In contrast, the last article in this journal on the
      definition of eHealth was published in 2006. This leads to the question whether
      the field itself has reached consensus about the definition and description of
      eHealth or whether it is in need for a new review of the literature and a new
      description of the rapidly changing field of eHealth. Since the JMIR community
      has successfully collaborated on the "CONSORT-eHealth" in the past, we would like
      to use the same strategy to explore the need for a new definition of eHealth and
      the creation of a taxonomy for this field. Therefore, we hereby submit a call to
      all JMIR-readers, to fill out a 4-question survey on their ideas about a refined
      eHealth definition. Based on these results, we will decide whether or not to
      engage in a systematic review. Logically, the entire JMIR community is invited to
      join us in our attempt to further elucidate the field of eHealth. 

PMID- 25768940
TI  - Semi-quantitative vs. volumetric determination of endolymphatic space in
      Meniere's disease using endolymphatic hydrops 3T-HR-MRI after intravenous
      gadolinium injection.
AB  - Magnetic resonance imaging enhances the clinical diagnosis of Meniere's disease.
      This is accomplished by in vivo detection of endolymphatic hydrops, which are
      graded using different semi-quantitative grading systems. We evaluated an
      established, semi-quantitative endolymphatic hydrops score and with a
      quantitative method for volumetric assessment of the endolymphatic size. 11
      patients with Meniere's disease and 2 healthy subjects underwent high resolution
      endolymphatic hydrops 3 Tesla MRI with highly T2 weighted FLAIR and T2DRIVE
      sequences. The degree of endolymphatic hydrops was rated semi-quantitatively and
      compared to the results of 3D-volumetry. Moreover, the grade of endolymphatic
      hydrops was correlated with pure tone audiometry. Semi-quantitative grading and
      volumetric evaluation of the endolymphatic hydrops are in accordance (r = 0.92)
      and the grade of endolymphatic hydrops correlates with pure tone audiometry.
      Patients with a sickness duration of >= 30 months showed a significant higher
      total labyrinth fluid volume (p = 0.03). Fast, semi-quantitative evaluation of
      endolymphatic hydrops is highly reliable compared to quantitative/volumetric
      assessment. Endolymphatic space is significantly higher in patients with longer
      sickness duration. 

PMID- 25768942
TI  - Assessment of water quality and identification of polluted risky regions based on
      field observations & GIS in the Honghe River watershed, China.
AB  - Water quality assessment at the watershed scale requires not only an
      investigation of water pollution and the recognition of main pollution factors,
      but also the identification of polluted risky regions resulted in polluted
      surrounding river sections. To realize this objective, we collected water
      samplings from 67 sampling sites in the Honghe River watershed of China with Grid
      GIS method to analyze six parameters including dissolved oxygen (DO), ammonia
      nitrogen (NH3-N), nitrate nitrogen (NO3-N), nitrite nitrogen (NO2-N), total
      nitrogen (TN) and total phosphorus (TP). Single factor pollution index and
      comprehensive pollution index were adopted to explore main water pollutants and
      evaluate water quality pollution level. Based on two evaluate methods, Geo
      statistical analysis and Geographical Information System (GIS) were used to
      visualize the spatial pollution characteristics and identifying potential
      polluted risky regions. The results indicated that the general water quality in
      the watershed has been exposed to various pollutants, in which TP, NO2-N and TN
      were the main pollutants and seriously exceeded the standard of Category III. The
      zones of TP, TN, DO, NO2-N and NH3-N pollution covered 99.07%, 62.22%, 59.72%,
      37.34% and 13.82% of the watershed respectively, and they were from medium to
      serious polluted. 83.27% of the watershed in total was polluted by comprehensive
      pollutants. These conclusions may provide useful and effective information for
      watershed water pollution control and management. 

PMID- 25768941
TI  - Comparative analysis of field-isolate and monkey-adapted Plasmodium vivax
      genomes.
AB  - Significant insights into the biology of Plasmodium vivax have been gained from
      the ability to successfully adapt human infections to non-human primates. P.
      vivax strains grown in monkeys serve as a renewable source of parasites for in
      vitro and ex vivo experimental studies and functional assays, or for studying in
      vivo the relapse characteristics, mosquito species compatibilities, drug
      susceptibility profiles or immune responses towards potential vaccine candidates.
      Despite the importance of these studies, little is known as to how adaptation to
      a different host species may influence the genome of P. vivax. In addition, it is
      unclear whether these monkey-adapted strains consist of a single clonal
      population of parasites or if they retain the multiclonal complexity commonly
      observed in field isolates. Here we compare the genome sequences of seven P.
      vivax strains adapted to New World monkeys with those of six human clinical
      isolates collected directly in the field. We show that the adaptation of P. vivax
      parasites to monkey hosts, and their subsequent propagation, did not result in
      significant modifications of their genome sequence and that these monkey-adapted
      strains recapitulate the genomic diversity of field isolates. Our analyses also
      reveal that these strains are not always genetically homogeneous and should be
      analyzed cautiously. Overall, our study provides a framework to better leverage
      this important research material and fully utilize this resource for improving
      our understanding of P. vivax biology. 

PMID- 25768943
TI  - Factors associated with a lack of pap smear utilization in women exposed in utero
      to diethylstilbestrol.
AB  - BACKGROUND: Women in the 1940s-1960s were prescribed diethylstilbestrol (DES), a
      nonsteroidal estrogen, to prevent miscarriages, but the practice was terminated
      after it was discovered that the daughters so exposed in utero were at increased
      risk for developing clear cell adenocarcinoma (CCA) of the vagina or cervix at
      early ages. Pap smear screening is one of the principal methods used to identify
      tumor development and is necessary in this group of women to maintain their
      health. Currently, little is known about the factors associated with
      nonutilization of this screening tool in this high-risk population of women.
      METHODS: National cohort data from the National Cancer Institute (NCI) DES
      Combined Cohort Follow-up Study during 1994, 1997, 2001, and 2006 were used to
      determine which factors were associated with Pap smear screening nonutilization
      in 2006 among DES-exposed and unexposed women. Self-reported questionnaire data
      from 2,861 DES-exposed and 1,027 unexposed women were analyzed using binary
      logistic regression models. RESULTS: DES exposure, not having a previous
      gynecologic dysplasia diagnosis, lack of insurance, originating cohort,
      increasing age, and previous screening behavior were all factors associated with
      not reporting a Pap smear examination in the 2006 questionnaire, although college
      education reduced nonutilization. CONCLUSIONS: Understanding which factors are
      associated with not acquiring a screening exam can help clinicians better
      identify which DES-exposed women are at risk for nonutilization and possibly
      tailor their standard of care to aid in the early detection of cervical and
      vaginal adenocarcinomas in this high-risk group.

PMID- 25768945
TI  - Early morphea simulating patch-stage mycosis fungoides.
AB  - Morphea is a rare fibrosing condition of the skin and underlying tissues
      characterized histopathologically by thickened collagen bundles throughout the
      dermis, loss of adnexal structures, and "fat trapping." In the early stages of
      morphea, the absence of the fully developed characteristic findings may cause
      diagnostic confusion for the practicing pathologist. The authors report an
      unusual case of early morphea misdiagnosed as patch-stage poikilodermatous
      mycosis fungoides (MF) based on the initial clinical, histopathologic, and
      molecular findings. However, as time elapsed, well-developed lesions revealed
      clinical and histopathologic features diagnostic of morphea. The authors report
      this case to illustrate that lesions of early morphea may simulate MF. Given the
      similarities in clinicopathologic presentation, dermatologists and
      dermatopathologists should be cautious not to inadvertently misinterpret early
      morphea as MF. 

PMID- 25768944
TI  - Iron prevents the development of experimental cerebral malaria by attenuating
      CXCR3-mediated T cell chemotaxis.
AB  - Cerebral malaria is a severe neurological complication of Plasmodium falciparum
      infection. Previous studies have suggested that iron overload can suppress the
      generation of a cytotoxic immune response; however, the effect of iron on
      experimental cerebral malaria (ECM) is yet unknown. Here we determined that the
      incidence of ECM was markedly reduced in mice treated with iron dextran.
      Protection was concomitant with a significant decrease in the sequestration of
      CD4+ and CD8+ T cells within the brain. CD4+ T cells demonstrated markedly
      decreased CXCR3 expression and had reduced IFNgamma-responsiveness, as indicated
      by mitigated expression of IFNgammaR2 and T-bet. Additional analysis of the
      splenic cell populations indicated that parenteral iron supplementation was also
      associated with a decrease in NK cells and increase in regulatory T cells.
      Altogether, these results suggest that iron is able to inhibit ECM pathology by
      attenuating the capacity of T cells to migrate to the brain. 

PMID- 25768947
TI  - Developing a Prediction Model for Post-Operative Delirium and Long-Term Outcomes
      Among Older Patients Receiving Elective Orthopedic Surgery: A Prospective Cohort
      Study in Taiwan.
AB  - This study aimed to develop a prediction model for post-operative delirium among
      older patients receiving elective orthopedic surgery and to evaluate its
      effectiveness in predicting long-term health outcomes. This prospective cohort
      study screened all subjects aged over 60 years who were admitted for elective
      orthopedic surgery in a tertiary medical center in Taiwan from April, 2011, to
      December, 2013. Demographic characteristics, surgery-related factors, and results
      of comprehensive geriatric assessment (CGA) were all used to develop the
      prediction model. Long-term health outcomes, including mortality, nursing home
      admission, and functional status in the first year after surgery, were used to
      further evaluate the effectiveness of the prediction model. Overall, 461 patients
      (median age, 73 years; interquartile range [IQR], 67-80 years; 42.3% males) were
      enrolled, and 37 patients (8.0%) developed post-operative delirium. Prediction
      models were developed on the basis of demographic characteristics and surgery
      related factors (model 1) and of demographic characteristics, surgery-related
      factors, and geriatric assessment variables (model 2). Although both models
      effectively predicted the occurrence of post-operative delirium, duration of post
      operative delirium, total hospital days, nursing home admission, and mortality,
      model 2 was more likely to differentiate cases with functional decline during the
      first year after surgery. In conclusion, a prediction model developed by using
      demographic characteristics, surgery-related factors, and results of CGA was
      highly predictive for post-operative delirium, as well as long-term health and
      functional outcomes. 

PMID- 25768946
TI  - Clonality and evolutionary history of rhabdomyosarcoma.
AB  - To infer the subclonality of rhabdomyosarcoma (RMS) and predict the temporal
      order of genetic events for the tumorigenic process, and to identify novel
      drivers, we applied a systematic method that takes into account germline and
      somatic alterations in 44 tumor-normal RMS pairs using deep whole-genome
      sequencing. Intriguingly, we find that loss of heterozygosity of 11p15.5 and
      mutations in RAS pathway genes occur early in the evolutionary history of the PAX
      fusion-negative-RMS (PFN-RMS) subtype. We discover several early mutations in non
      RAS mutated samples and predict them to be drivers in PFN-RMS including recurrent
      mutation of PKN1. In contrast, we find that PAX-fusion-positive (PFP) subtype
      tumors have undergone whole-genome duplication in the late stage of cancer
      evolutionary history and have acquired fewer mutations and subclones than PFN
      RMS. Moreover we predict that the PAX3-FOXO1 fusion event occurs earlier than the
      whole genome duplication. Our findings provide information critical to the
      understanding of tumorigenesis of RMS. 

PMID- 25768948
TI  - Clinical signs and progression of lesions in the gizzard are not influenced by
      inclusion of ground oats or whole wheat in the diet following experimental
      infection with pathogenic fowl adenovirus serotype 1.
AB  - In the present study the effects of dietary gizzard stimulation on the
      development and severity of adenoviral gizzard erosion were investigated. For
      this purpose, specific pathogen-free broilers were divided into six groups,
      investigating the influence of an oat-containing diet with higher fibre content,
      a whole wheat-containing diet and a control diet of nearly identical composition,
      but containing ground wheat. For each feed administered, one group of birds was
      experimentally infected on the 10th day of age by the oral route with virulent
      fowl adenovirus serotype 1 (FAdV-1), recently proven to induce gizzard erosions,
      while the respective negative control groups remained uninfected. Experimental
      feed was administered from 2 days post-infection onwards. No significant
      differences on gizzard health or in weight gain could be detected between
      uninfected control groups or between FAdV-1 infected groups that received
      different experimental feed. However, independent of the supplied diet, a
      significantly reduced weight gain was noted from 7 days post-infection onwards in
      FAdV-1 infected broilers compared to uninfected birds that received the same
      diet. Macroscopically, discolouration and erosion of the koilin layer and
      inflammation of the gizzard mucosa were observed in all FAdV-1 infected groups.
      Histologically, necrosis, degeneration of gizzard epithelial cells and multiple
      basophilic intranuclear inclusion bodies were observed. In summary, after
      experimental infection with FAdV-1 development of gizzard erosion in chickens was
      not influenced by the feeding regimes investigated. Therefore, it is unlikely
      that dietary gizzard stimulation influences the outcome of adenoviral gizzard
      erosion in vertically infected broilers. 

PMID- 25768949
TI  - Use of fully covered self-expandable metal stents for benign esophageal disorders
      in children.
AB  - PURPOSE: There is a lack of experience with fully covered self-expandable metal
      stents (SEMSs) for benign esophageal disorders in children. PATIENTS AND METHODS:
      Eleven children (six boys, five girls) with a median age of 30.5 months (range, 1
      month-11 years) who underwent treatment with SEMSs for a benign esophageal
      condition between February 2006 and January 2014 were recruited to this
      retrospective study. Etiologies included esophageal atresia with postoperative
      stricture (n=4), recurrent fistula (n=1), and/or anastomotic leak (n=1), as well
      as iatrogenic perforation of the esophagus following endoscopy (n=4) or
      laparoscopic fundoplication (n=1). As part of an interdisciplinary cooperation
      patients were jointly managed from the Department of Pediatric Surgery and
      Central Interdisciplinary Endoscopy at our institution. RESULTS: Median duration
      of individual stent placement was 29 days (range, 17-91 days). In 4 cases up to
      four different SEMSs were placed successively over time. There were no
      complications noted at stent insertion or removal. At follow-up, 6 patients (55%)
      were successfully treated without further intervention. Two children each (18%)
      underwent one single dilatation after stent removal and remained well afterward.
      Three patients (27%) did not improve following stenting and required definite
      surgery. Minor stent-related complications were noted in 5 cases (45%), including
      gastroesophageal reflux (n=2), silent stent migration (n=2), and pneumonia (n=1).
      CONCLUSIONS: SEMSs for benign esophageal disorders in children can be used safely
      and effectively in selected cases, including esophageal anastomotic strictures,
      esophageal leaks following primary surgery, or perforations postdilatation. An
      SEMS can be applied either as an emergency procedure or as an adjuvant treatment
      further to endoscopy or previous surgery. Establishment of a standardized
      approach in the pediatric population is mandatory.

PMID- 25768950
TI  - What do studies of insect polyphenisms tell us about nutritionally-triggered
      epigenomic changes and their consequences?
AB  - Many insects are capable of remarkable changes in biology and form in response to
      their environment or diet. The most extreme example of these are polyphenisms,
      which are when two or more different phenotypes are produced from a single
      genotype in response to the environment. Polyphenisms provide a fascinating
      opportunity to study how the environment affects an animal's genome, and how this
      produces changes in form. Here we review the current state of knowledge of the
      molecular basis of polyphenisms and what can be learnt from them to understand
      how nutrition may influence our own genomes. 

PMID- 25768951
TI  - Changes in composition of caecal microbiota associated with increased colon
      inflammation in interleukin-10 gene-deficient mice inoculated with Enterococcus
      species.
AB  - Human inflammatory bowel disease (IBD) is a chronic intestinal disease where the
      resident microbiota contributes to disease development, yet the specific
      mechanisms remain unclear. Interleukin-10 gene-deficient (Il10-/-) mice develop
      inflammation similar to IBD, due in part to an inappropriate response to
      commensal bacteria. We have previously reported changes in intestinal morphology
      and colonic gene expression in Il10-/- mice in response to oral bacterial
      inoculation. In this study, we aimed to identify specific changes in the caecal
      microbiota associated with colonic inflammation in these mice. The microbiota was
      evaluated using pyrotag sequencing, denaturing gradient gel electrophoresis
      (DGGE) and quantitative real-time PCR. Microbiota profiles were influenced by
      genotype of the mice and by bacterial inoculation, and a strong correlation was
      observed between the microbiota and colonic inflammation scores. Although un
      inoculated Il10-/- and C57 mice had similar microbiota communities, bacterial
      inoculation resulted in different changes to the microbiota in Il10-/- and C57
      mice. Inoculated Il10-/- mice had significantly less total bacteria than un
      inoculated Il10-/- mice, with a strong negative correlation between total
      bacterial numbers, relative abundance of Escherichia/Shigella, microbiota
      diversity, and colonic inflammation score. Our results show a putative causative
      role for the microbiota in the development of IBD, with potentially key roles for
      Akkermansia, or for Bacteroides, Helicobacter, Parabacteroides, and Alistipes,
      depending on the composition of the bacterial inoculum. These data support the
      use of bacterially-inoculated Il10-/- mice as an appropriate model to investigate
      human IBD. 

PMID- 25768952
TI  - Effectiveness of dietary allergen exclusion therapy on eosinophilic colitis in
      Chinese infants and young children <= 3 years of age.
AB  - Eosinophilic colitis is a well recognized clinical entity mainly associated with
      food allergies. Empiric treatment options include dietary allergen exclusion
      (extensively hydrolyzed protein formula and elimination diet), anti-allergy
      medications (antihistamines and leukotriene receptor antagonists) and
      corticosteroids. We evaluated the effectiveness of dietary antigen exclusion on
      clinical remission of eosinophilic colitis in infants and young children. We
      retrospectively reviewed charts of all infants and children <=3 years of age who
      were diagnosed with eosinophilic colitis (defined as mucosal eosinophilia >=20
      hpf-1) from 1 January 2011 to 31 December 2013 at a tertiary children's hospital
      in China. Forty-nine children were identified with eosinophilic colitis.
      Elemental formula, simple elimination diet or combination therapy resulted in
      clinical improvement in 75%, 88.2% and 80% of patients, respectively. In
      conclusion, eosinophilic colitis in infants and children <=3 years of age
      responded well to dietary allergen exclusion. 

PMID- 25768953
TI  - Phase angle and handgrip strength are sensitive early markers of energy intake in
      hypophagic, non-surgical patients at nutritional risk, with contraindications to
      enteral nutrition.
AB  - The assessment of nutritional intakes during hospitalization is crucial, as it is
      known that nutritional status tends to worsen during the hospital stay, and this
      can lead to the negative consequences of malnutrition. International guidelines
      recommend the use of parenteral nutrition (PN) in hypophagic, non-surgical
      patients at nutritional risk, with contraindications to enteral nutrition.
      However, to date, there are no published data regarding either energy intake or
      objective measurements associated with it in this patient population. The aim of
      the present exploratory methodological study was to evaluate whether phase angle
      (PhA) and handgrip strength normalized for skeletal muscle mass (HG/SMM) are
      sensitive early markers of energy intake in hypophagic, non-surgical patients at
      nutritional risk, with contraindications to enteral nutrition. We evaluated 30
      eligible patients, who were treated with personalized dietary modifications and
      supplemental PN for at least one week during hospitalization. In a liner
      regression model adjusted for age, gender, basal protein intake and the basal
      value of each variable, a trend toward improvement of PhA and preservation of
      HG/SMM was observed in patients satisfying the estimated calorie requirements (N
      = 20), while a significant deterioration of these parameters occurred in those
      who were not able to reach the target (N = 10). The mean adjusted difference and
      95% CI were +1.4 degrees  (0.5-2.3) (p = 0.005) for PhA and +0.23 (0.20-0.43) (p
      = 0.033) for HG/SMM. A significant correlation between PhA and HG/SMM variations
      was also observed (r = 0.56 (95% CI, 0.23-0.77); p = 0.0023). PhA and HG/SMM were
      able to distinguish between hypophagic, non-surgical patients at nutritional risk
      who satisfied their estimated caloric requirements and those who did not after a
      one-week personalized nutritional support. Clinical studies are warranted, in
      order to verify these preliminary observations and to validate the role of PhA
      variations as early markers of anabolic/catabolic fluctuations. 

PMID- 25768954
TI  - Food group and micronutrient intake adequacy among children, adults and elderly
      women in Greece.
AB  - The aim of the present study was to record the percentage of children, adults and
      elderly women in Greece meeting food and micronutrient intake recommendations.
      Additionally, the present study was aiming to identify the main food contributors
      of micronutrient intakes and assess the degree up to which meeting food intake
      recommendations also ensures micronutrient intake adequacy. Dietary intake data
      from three studies conducted in Greece (on 9-13-year-old children; 40-60-year-old
      adults; and 50-75-year-old women) were used to estimate mean intakes, the
      percentages of subjects meeting food and nutrient intake recommendations and the
      contribution of six core food groups to nutrient intake adequacy. The present
      study showed that more than 50% of children, adults and elderly women were
      failing to consume the recommended portions of vegetables, dairy and grains.
      Furthermore, children and adults consuming the recommended portions of individual
      core food groups had significantly lower percentages of inadequate micronutrient
      intakes compared to their counterparts not meeting food intake recommendations (p
      < 0.05). Nevertheless, even among those consuming the recommended portions from a
      specific core food group, the recommended intake of the corresponding
      micronutrient (for which this food group is the main contributor) was not always
      met. Indicatively, 18.2%-44.1% and 4.2%-7.0% of the populations under study were
      not meeting calcium and vitamin C intake recommendations, although they were
      consuming the recommended portions of dairy and fruits, respectively. In
      conclusion, these findings highlight the importance for public health policy
      makers to take all necessary initiatives to support the population in achieving
      the recommended intakes from all core food groups, but also emphasize on food
      variety to ensure adequate intake for all micronutrients. 

PMID- 25768955
TI  - Genetics of common forms of heart failure: challenges and potential solutions.
AB  - PURPOSE OF REVIEW: In contrast to many other human diseases, the use of genome
      wide association studies (GWAS) to identify genes for heart failure (HF) has had
      limited success. We will discuss the underlying challenges as well as potential
      new approaches to understanding the genetics of common forms of HF. RECENT
      FINDINGS: Recent research using intermediate phenotypes, more detailed and
      quantitative stratification of HF symptoms, founder populations and novel animal
      models has begun to allow researchers to make headway toward explaining the
      genetics underlying HF using GWAS techniques. SUMMARY: By expanding analyses of
      HF to improved clinical traits, additional HF classifications and innovative
      model systems, the intractability of human HF GWAS should be ameliorated
      significantly.

PMID- 25768956
TI  - Therapeutic applications of noncoding RNAs.
AB  - PURPOSE OF REVIEW: In this review, we summarize the basic principles underlying
      the therapeutic use of nonprotein coding (nc)RNAs, such as microRNA (miRNA) and
      long noncoding RNA, in the cardiovascular field, focusing, where possible, on
      recent advances that may lead to translation to the clinic for heart failure.
      RECENT FINDINGS: The number of individual miRNAs associated with a given aspect
      of heart disease is increasing rapidly, as is the data on miRNA profiles in
      normal and diseased myocardium. Less is known on the role of long noncoding RNA,
      and to date only a few have been studied in the heart. Novel oligonucleotide
      based therapies have started to trickle into the clinic, but strategies focusing
      on ncRNA are still in a clinical/preclinical trial phase. SUMMARY: The discovery
      of functional ncRNAs is leading to a better understanding of the mechanisms
      underlying cardiovascular physiology. Dysregulation of ncRNAs is being
      increasingly associated with many diseases affecting the heart and in certain
      instances may have a pathogenic role. Therapeutic intervention aimed at opposing
      ncRNA misexpression has been widely demonstrated to be effective in blunting
      disease in animal models, and may thus have potential in the clinical setting.

PMID- 25768957
TI  - Temperature dependent mechanical property of PZT film: an investigation by
      nanoindentation.
AB  - Load-depth curves of an unpoled Lead Zirconate Titanate (PZT) film composite as a
      function of temperature were measured by nanoindentation technique. Its reduce
      modulus and hardness were calculated by the typical Oliver-Pharr method. Then the
      true modulus and hardness of the PZT film were assessed by decoupling the
      influence of substrate using methods proposed by Zhou et al. and Korsunsky et
      al., respectively. Results show that the indentation depth and modulus increase,
      but the hardness decreases at elevated temperature. The increasing of indentation
      depth and the decreasing of hardness are thought to be caused by the decreasing
      of the critical stress needed to excite dislocation initiation at high
      temperature. The increasing of true modulus is attributed to the reducing of
      recoverable indentation depth induced by back-switched domains. The influence of
      residual stress on the indentation behavior of PZT film composite was also
      investigated by measuring its load-depth curves with pre-load strains. 

PMID- 25768958
TI  - The value of certification.

PMID- 25768959
TI  - STN News and Notes.

PMID- 25768960
TI  - Transitioning the complex trauma patient from the ICU: acute care nurses'
      perceptions of readiness.
AB  - Trauma centers improve patient outcomes through the provision of expert care by
      trauma surgeons and nurses. While the American College of Surgeons stipulates
      that trauma centers must have qualified nurses, there is no clear definition of
      qualified, nor is there a recommendation for trauma nurse readiness beyond the
      emergency department or intensive care. In a newly designated level II trauma
      center, it was recognized that nurses were unprepared to provide care to complex
      trauma patients. This study explored nurses' perceptions of their knowledge,
      skills and confidence in complex trauma care utilizing a novel transitional care
      model. 

PMID- 25768961
TI  - The effect of methodology in determining disparities in in-hospital mortality of
      trauma patients based on payer source.
AB  - A retrospective registry review of adult patients admitted to a Level I trauma
      center sought to determine whether results regarding in-hospital mortality
      associated with payer source vary on the basis of methodology. Patients were
      categorized into 4 literature-derived definitions (Definition 1: insured and
      uninsured; Definition 2: commercially insured, publicly insured, and uninsured;
      Definition 3: commercially insured, Medicaid, Medicare, and uninsured; and
      Definition 4: commercially insured, Medicaid, and uninsured). In-hospital
      mortality differences were found in Definitions 2 and 3, and when reclassifying
      dual-eligible Medicare/Medicaid into socioeconomic and age indicators. Variations
      in methodology culminated in results that could be interpreted with differing
      conclusions. 

PMID- 25768962
TI  - Nurse led telephone follow-up improves satisfaction in motorcycle trauma
      patients.
AB  - Telephone follow-up (TFU) is a good tool for providing transfer of health
      education, dealing with symptomatic concerns, early recognition of potential
      complications, and reassuring the patient after discharge. Telephone follow-up
      may also decrease knowledge deficits, increase communication improving patient
      satisfaction and patient outcomes to include decreased emergency department
      visits and hospital readmissions. An advanced practice nurse-led TFU program
      involving 59 motorcycle trauma patients discharged to home demonstrates how
      effective TFU can improve patient satisfaction in motorcycle trauma. 

PMID- 25768963
TI  - Use of Six Sigma strategies to pull the line on central line-associated
      bloodstream infections in a neurotrauma intensive care unit.
AB  - The creation of a consistent culture of safety and quality in an intensive care
      unit is challenging. We applied the Six Sigma Define-Measure-Analyze-Improve
      Control (DMAIC) model for quality improvement (QI) to develop a long-term
      solution to improve outcomes in a high-risk neurotrauma intensive care unit. We
      sought to reduce central line utilization as a cornerstone in preventing central
      line-associated bloodstream infections (CLABSIs). This study describes the
      successful application of the DMAIC model in the creation and implementation of
      evidence-based quality improvement designed to reduce CLABSIs to below national
      benchmarks. 

PMID- 25768964
TI  - Pharmacist's impact on acute pain management during trauma resuscitation.
AB  - The timely administration of analgesics is crucial to the comprehensive
      management of trauma patients. When an emergency department (ED) pharmacist
      participates in trauma resuscitation, the pharmacist acts as a medication
      resource for trauma team members and facilitates the timely administration of
      analgesics. This study measured the impact of a pharmacist on time to first
      analgesic dose administered during trauma resuscitation. All adult (>18 years)
      patients who presented to this level II trauma center via activation of the
      trauma response system between January 1, 2009, and May 31, 2013, were screened
      for eligibility. For inclusion, patients must have received intravenous fentanyl,
      morphine, or hydromorphone in the trauma bay. The time to medication
      administration was defined as the elapsed time from ED arrival to administration
      of first analgesic. There were 1328 trauma response system activations during the
      study period; of which 340 patients were included. The most common analgesic
      administered was fentanyl (62% in both groups). When a pharmacist was
      participating, the mean time to first analgesic administered was decreased (17 vs
      21 minutes; P = .03). Among the 78% of patients with documented pain scores, the
      overall mean reduction in pain scores from ED arrival to ED discharge was similar
      between the 2 groups. There was a 2.4 point reduction with a pharmacist versus
      2.7 without a pharmacist, using a 0 to 10 numeric pain rating scale. The
      participation of a clinical pharmacist during trauma resuscitation significantly
      decreased the time to first analgesic administration in trauma patients. The
      results of this study supplement the literature supporting the integration of
      clinical ED pharmacists on trauma teams. 

PMID- 25768965
TI  - A rewarding teaching experience: taking ATCN to the USNS MERCY (T-AH 19).
AB  - Navy nurses are challenged to maintain trauma competency between deployment
      settings. The Advanced Trauma Care for Nurses (ATCN) course provides trauma nurse
      training to Navy nurses. Presenting ATCN in a nontraditional environment aboard a
      Naval vessel during a training exercise provided a rewarding teaching and
      learning experience. 

PMID- 25768966
TI  - Impact of nursing education by a pharmacist on sedation practice in a trauma
      surgical intensive care unit.
AB  - INTRODUCTION: Benefits of pharmacist-provided education on nurse-driven sedation
      protocols have not been assessed. METHODS: Trauma intensive care unit nurses
      received pharmacist-provided education on the hospital's sedation protocol.
      Sedation outcomes were assessed for patients in the preeducation (n = 29) and
      posteducation (n = 33) groups. RESULTS: The primary outcome of sedation scores at
      goal was not significantly different (41% vs 60%; P = .169), while more patients
      experienced oversedation (50% vs 32%; P = .013) in the pre- vs posteducation
      groups, respectively. No patient experienced self-extubation. CONCLUSIONS:
      Despite similar achievement of goal sedation scores before and after pharmacist
      provided education, the posteducation group experienced fewer incidences of
      oversedation with no difference in self-extubation.

PMID- 25768967
TI  - Evaluation and management of blunt traumatic aortic injury: a practice management
      guideline from the Eastern Association for the Surgery of Trauma.
AB  - BACKGROUND: Blunt traumatic aortic injury (BTAI) is the second most common cause
      of death in trauma patients. Eighty percent of patients with BTAI will die before
      reaching a trauma center. The issues of how to diagnose, treat, and manage BTAI
      were &filig;rst addressed by the Eastern Association for the Surgery of Trauma
      (EAST) in the practice management guidelines on this topic published in 2000.
      Since that time, there have been advances in the management of BTAI. As a result,
      the EAST guidelines committee decided to develop updated guidelines for this
      topic using the Grading of Recommendations, Assessment, Development and
      Evaluation (GRADE) framework recently adopted by EAST. METHODS: A systematic
      review of the MEDLINE database using PubMed was performed. The search retrieved
      English language articles regarding BTAI from 1998 to 2013. Letters to the
      editor, case reports, book chapters, and review articles were excluded. Topics of
      investigation included imaging to diagnose BTAI, type of operative repair, and
      timing of operative repair. RESULTS: Sixty articles were identi&filig;ed. Of
      these, 51 articles were selected to construct the guidelines. CONCLUSION: There
      have been changes in practice since the publication of the previous guidelines in
      2000. Computed tomography of the chest with intravenous contrast is strongly
      recommended to diagnose clinically signi&filig;cant BTAI. Endovascular repair is
      strongly recommended for patients without contraindications. Delayed repair of
      BTAI is suggested, with the stipulation that effective blood pressure control
      must be used in these patients.

PMID- 25768968
TI  - 0.9% saline induced hyperchloremic acidosis.
AB  - In the acute care setting, the type and amount of fluid administered has a
      significant impact on patient outcomes. In particular, 0.9% saline infusions are
      known to cause or exacerbate hyperchloremia. The studies presented evaluate
      possible complications from 0.9% saline infusions. These studies compared
      administration of 0.9% saline with lactated ringer or plasmalyte in the acute
      care setting. In each trial, the patients who were randomized to receive 0.9%
      saline infusions had a more severe acidosis from increased serum chloride levels.
      From the available data, chloride-restrictive intravenous fluid such as
      plasmalyte appears to reduce acid-base disturbances and improve patient outcomes.

PMID- 25768971
TI  - Improved investigations in drug safety by more in-depth individual
      pharmacokinetics using high-resolution mass spectrometry.

PMID- 25768970
TI  - Human adipose cells in vitro are either refractory or responsive to insulin,
      reflecting host metabolic state.
AB  - While intercellular communication processes are frequently characterized by
      switch-like transitions, the endocrine system, including the adipose tissue
      response to insulin, has been characterized by graded responses. Yet here
      individual cells from adipose tissue biopsies are best described by a switch-like
      transition between the basal and insulin-stimulated states for the trafficking of
      the glucose transporter GLUT4. Two statistically-defined populations best
      describe the observed cellular heterogeneity, representing the fractions of
      refractive and responsive adipose cells. Furthermore, subjects exhibiting high
      systemic insulin sensitivity indices (SI) have high fractions of responsive
      adipose cells in vitro, while subjects exhibiting decreasing SI have increasing
      fractions of refractory cells in vitro. Thus, a two-component model best
      describes the relationship between cellular refractory fraction and subject SI.
      Since isolated cells exhibit these different response characteristics in the
      presence of constant culture conditions and milieu, we suggest that a
      physiological switching mechanism at the adipose cellular level ultimately drives
      systemic SI. 

PMID- 25768972
TI  - Evaluating external contamination of polybrominated diphenyl ethers in human
      hair: clinical and research implications.
AB  - BACKGROUND: Human hair is a well-validated matrix for detecting a variety of
      xenobiotics, including drugs of abuse (cocaine, tetrahydrocannabinol, and
      morphine) and fatty acid ethyl ethers. Recent studies have shown that hair can
      also be useful in determining an individual's exposure to polybrominated diphenyl
      ethers (PBDEs), flame retardants that contaminate the dust in our daily
      environment. Hair processing before assay varies with each analyte; in
      particular, the wash protocol must be optimized to remove external contaminants
      while not affecting levels of the chemical of interest. The aim of this study was
      to determine whether hair needs to be washed before analysis for PBDEs, and if
      so, which protocol is most effective to ensure that the level of PBDEs is neither
      overestimated nor underestimated. METHOD: Individual hair samples from 10 adults
      (5 men and 5 women) were subjected to 4 different wash protocols: (1) no wash,
      (2) water, (3) 10% sodium dodecyl sulfate (SDS), and (4) hexane. Both the washes
      and hair were analyzed for 8 PBDEs by gas chromatography/mass spectrometry.
      RESULTS: The sum of PBDEs (SigmaPBDEs) in the washes was (1) no wash: 0 pg/mg,
      (2) water: 0.39 +/- 0.19 (mean +/- SEM), (3) 10% SDS: 1.34 +/- 0.68, and (4)
      hexane: 1.92 +/- 0.87. The SigmaPBDEs in the hair were: (1) no wash: 20.32 +/-
      3.05, (2) water: 20.30 +/- 2.41, (3) 10% SDS: 19.27 +/- 1.87, and (4) hexane:
      16.91 +/- 2.89. Washing with water, 10% SDS, and hexane decreased the PBDE levels
      by 1.9%, 7%, and 11.4%, respectively (P < 0.05). CONCLUSIONS: Thus, of the washes
      evaluated, water is the wash that had the least effect on total PBDE
      concentrations, providing the best evaluation of an individual's exposure to
      PBDEs.

PMID- 25768973
TI  - Trigger chemistries for better industrial formulations.
AB  - In recent years, innovations and consumer demands have led to increasingly
      complex liquid formulations. These growing complexities have provided industrial
      players and their customers access to new markets through product
      differentiation, improved performance, and compatibility/stability with other
      products. One strategy for enabling more complex formulations is the use of
      active encapsulation. When encapsulation is employed, strategies are required to
      effect the release of the active at the desired location and time of action. One
      particular route that has received significant academic research effort is the
      employment of triggers to induce active release upon a specific stimulus, though
      little has translated for industrial use to date. To address emerging industrial
      formulation needs, in this review, we discuss areas of trigger release
      chemistries and their applications specifically as relevant to industrial use. We
      focus the discussion on the use of heat, light, shear, and pH triggers as applied
      in several model polymeric systems for inducing active release. The goal is that
      through this review trends will emerge for how technologies can be better
      developed to maximize their value through industrial adaptation. 

PMID- 25768974
TI  - Safety of Gastrointestinal Endoscopy With Conscious Sedation in Patients With and
      Without Obstructive Sleep Apnea.
AB  - BACKGROUND AND STUDY AIMS: Patients with obstructive sleep apnea (OSA) undergoing
      endoscopy with sedation are considered by practitioners to be at a higher risk
      for cardiopulmonary complications. The aim of the present study was to evaluate
      the safety of conscious sedation in patients with OSA undergoing gastrointestinal
      endoscopy. PATIENTS AND METHODS: This is an IRB-approved prospective cohort study
      performed at the James A. Haley VA. A total of 248 patients with confirmed
      moderate or severe OSA by polysomnography and 252 patients without OSA were
      enrolled. Cardiopulmonary variables such as heart rate, blood pressure, and level
      of blood oxygen saturation were recorded at 3-minute intervals throughout the
      endoscopic procedure. RESULTS: In total, 302 colonoscopies, 119
      esophagogastroduodenoscopies, 6 flexible sigmoidoscopies, and 60
      esophagogastroduodenoscopy/colonoscopies were performed. None of the patients in
      the study required endotracheal intubation, pharmacologic reversal, or
      experienced an adverse outcome as a result of changes in blood pressure, heart
      rate, or blood oxygen saturation. There were no significant differences in the
      rate of tachycardia (P=0.749), bradycardia (P=0.438), hypotension
      (systolic/diastolic, P=0.460; mean arterial pressure, P=0.571), or hypoxia
      (P=0.787) between groups. The average length of time spent in each procedure and
      the average dose of sedation administered also did not differ significantly
      between the groups. CONCLUSIONS: Despite the presumed increased risk of
      cardiopulmonary complications, patients with OSA who undergo endoscopy with
      conscious sedation have clinically insignificant variations in cardiopulmonary
      parameters that do not differ from those without OSA. Costly preventative
      measures in patients with OSA are not warranted.

PMID- 25768975
TI  - Optimizing sampling device for the fecal immunochemical test increases
      colonoscopy yields in colorectal cancer screening.
AB  - The fecal immunochemical test (FIT) that quantifies hemoglobin concentration is
      reported to be better than qualitative FIT and the reason for its superiority has
      not been interpreted. To evaluate and understand the superiority of quantitative
      FIT, a representative randomly selected population (n=2355) in Jiashan County,
      China, aged 40-74 years was invited for colorectal cancer screening in 2012.
      Three fecal samples were collected from each participant by one optimized and two
      common sampling devices, and then tested by both quantitative and qualitative
      FITs. Colonoscopy was provided independently to all participants. The
      performances of five featured screening strategies were compared. A total of 1020
      participants were eligible. For screening advanced neoplasia, the positive
      predictive value (PPV) and the specificity of the strategy that tested one sample
      dissolved in an optimized device by quantitative FIT [PPV=40.8%, 95% confidence
      interval (CI): 27.1-54.6; specificity=96.8%, 95% CI: 95.7-98.0] were
      significantly improved over the strategy that tested one sample dissolved in the
      common device by qualitative FIT (PPV=14.1%, 95% CI: 8.2-19.9; specificity=87.9%,
      95% CI: 85.8-89.9), whereas the sensitivity did not differ (39.2 and 37.3%,
      P=0.89). Similar disparity in performance was observed between the strategies
      using qualitative FIT to test one sample dissolved in optimized (PPV=29.5%, 95%
      CI: 18.1-41.0; specificity=95.3%, 95% CI: 94.0-96.7) versus common sampling
      devices. High sensitivity for advanced neoplasia was observed in the strategy
      that tested two samples by qualitative FIT (52.9%, 95% CI: 39.2-66.6).
      Quantitative FIT is better than qualitative FIT for screening advanced colorectal
      neoplasia. However, the fecal sampling device might contribute most significantly
      toward the superiority of quantitative FIT. 

PMID- 25768976
TI  - Statins in the chemoprevention of colorectal cancer in established animal models
      of sporadic and colitis-associated cancer.
AB  - Despite the availability of effective surveillance for colorectal cancer with
      colonoscopy, chemoprevention might be an acceptable alternative. Statins are
      potent inhibitors of cholesterol biosynthesis. In clinical trials, statins have
      been found to be beneficial in the primary and secondary prevention of coronary
      heart disease. However, the overall benefits observed with statins appear to be
      greater than what might be expected from changes in lipid levels alone,
      suggesting effects beyond cholesterol lowering. This systematic review aimed to
      gather information on the possible chemopreventive role of statins in preventing
      carcinogenesis and tumor promotion by a diverse array of mechanisms in both
      sporadic and colitis-associated cancer in animal models. The MEDLINE database was
      thoroughly searched using the following keywords: 'statin, HMG-CoA reductase
      inhibitor, colon cancer, mice, rats, chemoprevention, colitis-associated cancer'.
      Additional articles were gathered and evaluated. There are a lot of clinical
      studies and meta-analyses, as well as a plethora of basic research studies
      implementing cancer cell lines and animal models, on the chemopreventive role of
      statins in colorectal cancer (CRC). However, data derived from clinical studies
      are inconclusive, yet they show a tendency toward a beneficial role of statins
      against CRC pathogenesis. Thus, more research on the molecular pathways of CRC
      tumorigenesis as related to statins is warranted to uncover new mechanisms and
      compare the effect of statins on both sporadic and colitis-associated cancer in
      animal models. Basic science results could fuel exclusive colitis-associated
      cancer clinical trials to study the chemopreventive effects of statins and to
      differentiate between their effects on the two types of CRCs in humans. 

PMID- 25768977
TI  - Smaller = denser, and the brain knows it: natural statistics of object density
      shape weight expectations.
AB  - If one nondescript object's volume is twice that of another, is it necessarily
      twice as heavy? As larger objects are typically heavier than smaller ones, one
      might assume humans use such heuristics in preparing to lift novel objects if
      other informative cues (e.g., material, previous lifts) are unavailable. However,
      it is also known that humans are sensitive to statistical properties of our
      environments, and that such sensitivity can bias perception. Here we asked
      whether statistical regularities in properties of liftable, everyday objects
      would bias human observers' predictions about objects' weight relationships. We
      developed state-of-the-art computer vision techniques to precisely measure the
      volume of everyday objects, and also measured their weight. We discovered that
      for liftable man-made objects, "twice as large" doesn't mean "twice as heavy":
      Smaller objects are typically denser, following a power function of volume.
      Interestingly, this "smaller is denser" relationship does not hold for natural or
      unliftable objects, suggesting some ideal density range for objects designed to
      be lifted. We then asked human observers to predict weight relationships between
      novel objects without lifting them; crucially, these weight predictions
      quantitatively match typical weight relationships shown by similarly-sized
      objects in everyday environments. These results indicate that the human brain
      represents the statistics of everyday objects and that this representation can be
      quantitatively abstracted and applied to novel objects. Finally, that the brain
      possesses and can use precise knowledge of the nonlinear association between size
      and weight carries important implications for implementation of forward models of
      motor control in artificial systems. 

PMID- 25768979
TI  - Society for Maternal Fetal Medicine 2015 Annual Pregnancy Meeting supplemental
      episode 6: Post-Meeting Round-Up (Part 2 of 3).

PMID- 25768978
TI  - Prospectively quantifying the propensity for atrial fibrillation: a mechanistic
      formulation.
AB  - The goal of this study was to determine quantitative relationships between
      electrophysiologic parameters and the propensity of cardiac tissue to undergo
      atrial fibrillation. We used a computational model to simulate episodes of
      fibrillation, which we then characterized in terms of both their duration and the
      population dynamics of the electrical waves which drove them. Monte Carlo
      sampling revealed that episode durations followed an exponential decay
      distribution and wave population sizes followed a normal distribution. Half-lives
      of reentrant episodes increased exponentially with either increasing tissue area
      to boundary length ratio (A/BL) or decreasing action potential duration (APD),
      resistance (R) or capacitance (C). We found that the qualitative form of
      fibrillatory activity (e.g., multi-wavelet reentry (MWR) vs. rotors) was
      dependent on the ratio of resistance and capacitance to APD; MWR was reliably
      produced below a ratio of 0.18. We found that a composite of these
      electrophysiologic parameters, which we term the fibrillogenicity index (Fb =
      A/(BL*APD*R*C)), reliably predicted the duration of MWR episodes (r2 = 0.93).
      Given that some of the quantities comprising Fb are amenable to manipulation (via
      either pharmacologic treatment or catheter ablation), these findings provide a
      theoretical basis for the development of titrated therapies of atrial
      fibrillation. 

PMID- 25768980
TI  - Development of 4D mathematical observer models for the task-based evaluation of
      gated myocardial perfusion SPECT.
AB  - This paper presents two 4D mathematical observer models for the detection of
      motion defects in 4D gated medical images. Their performance was compared with
      results from human observers in detecting a regional motion abnormality in
      simulated 4D gated myocardial perfusion (MP) SPECT images. The first 4D
      mathematical observer model extends the conventional channelized Hotelling
      observer (CHO) based on a set of 2D spatial channels and the second is a proposed
      model that uses a set of 4D space-time channels. Simulated projection data were
      generated using the 4D NURBS-based cardiac-torso (NCAT) phantom with 16
      gates/cardiac cycle. The activity distribution modelled uptake of (99m)Tc MIBI
      with normal perfusion and a regional wall motion defect. An analytical projector
      was used in the simulation and the filtered backprojection (FBP) algorithm was
      used in image reconstruction followed by spatial and temporal low-pass filtering
      with various cut-off frequencies. Then, we extracted 2D image slices from each
      time frame and reorganized them into a set of cine images. For the first model,
      we applied 2D spatial channels to the cine images and generated a set of feature
      vectors that were stacked for the images from different slices of the heart. The
      process was repeated for each of the 1,024 noise realizations, and CHO and
      receiver operating characteristics (ROC) analysis methodologies were applied to
      the ensemble of the feature vectors to compute areas under the ROC curves (AUCs).
      For the second model, a set of 4D space-time channels was developed and applied
      to the sets of cine images to produce space-time feature vectors to which the CHO
      methodology was applied. The AUC values of the second model showed better
      agreement (Spearman's rank correlation (SRC) coefficient = 0.8) to human observer
      results than those from the first model (SRC coefficient = 0.4). The agreement
      with human observers indicates the proposed 4D mathematical observer model
      provides a good predictor of the performance of human observers in detecting
      regional motion defects in 4D gated MP SPECT images. The result supports the use
      of the observer model in the optimization and evaluation of 4D image
      reconstruction and compensation methods for improving the detection of motion
      abnormalities in 4D gated MP SPECT images. 

PMID- 25768981
TI  - Epistemological depth in a GM crops controversy.
AB  - This paper examines the scientific controversy over the yields of genetically
      modified [GM] crops as a case study in epistemologically deep disagreements.
      Appeals to "the evidence" are inadequate to resolve such disagreements; not
      because the interlocutors have radically different metaphysical views (as in
      cases of incommensurability), but instead because they assume rival
      epistemological frameworks and so have incompatible views about what kinds of
      research methods and claims count as evidence. Specifically, I show that, in the
      yield debate, proponents and opponents of GM crops cite two different sets of
      claims as evidence, which correspond to two rival epistemological frameworks,
      classical experimental epistemology and Nancy Cartwright's evidence for use. I go
      on to argue that, even if both sides of the debate accepted Cartwright's view,
      they might still disagree over what counts as evidence, because evidence for use
      ties standards of evidence to what is sometimes called the "context of
      application." 

PMID- 25768984
TI  - High performance anion exchange chromatography with pulsed amperometric detection
      (HPAEC-PAD) for the sensitive determination of hyaluronan oligosaccharides.
AB  - High performance anion exchange chromatography (HPAEC) with pulsed amperometric
      detection (PAD) was optimized for the analysis of oligosaccharides derived from
      the extracellular matrix component hyaluronan. Using this sensitive approach, the
      separation of oligosaccharides consisting of two (molecular weight ca. 0.8 kDa)
      up to 25-30 (molecular weight: ca. 9.5-11.4 kDa) disaccharide moieties was
      possible. Standard oligosaccharides (comprising 2-4 repetitive disaccharides)
      were detectable at very low amounts of 0.2-0.3 pmol (20-30 nM). Including 10 min
      of column equilibration, a complex mixture of low molecular weight hyaluronan can
      be analyzed within 40 min. The HPAEC method was successfully applied to the study
      of the size-dependency of both the action of bovine testicular hyaluronidase
      (BTH) and the precipitation of hyaluronan by cetyltrimethylammonium bromide
      (CTAB), a physicochemical reaction often used for the determination of hyaluronan
      and hyaluronidase activity.

PMID- 25768982
TI  - Evidence-based psychological treatments for mental disorders: modifiable barriers
      to access and possible solutions.
AB  - The prevalence of mental disorders is high and appears to be growing, yet the
      majority of individuals who meet diagnostic criteria for a mental disorder are
      not able to access an adequate treatment. While evidence-based psychological
      treatments (EBPTs) are effective single or adjunctive treatments for mental
      disorders, there is also evidence that access to these treatments is diminishing.
      We seek to highlight modifiable barriers to these problems at the patient,
      therapist, treatment, organization and government-levels of analysis. A range of
      solutions to each set of contributors is offered and domains for future research
      are highlighted. In particular, we focus on the need to continue to work toward
      innovation in treatment development while also solving the difficulties relating
      to the dissemination of EBPTs. Several relatively new concepts in the field will
      be discussed (implementation cliff, program drift, voltage drop and deployment
      treatment development) and we contrast America and England as examples of
      government-level processes that are in the process of major change with respect
      to EBPTs. We conclude that there is a need for people in our field to become more
      knowledgeable about, and get involved in, shaping public policy. 

PMID- 25768983
TI  - Transcriptome sequencing reveals potential mechanism of cryptic 3' splice site
      selection in SF3B1-mutated cancers.
AB  - Mutations in the splicing factor SF3B1 are found in several cancer types and have
      been associated with various splicing defects. Using transcriptome sequencing
      data from chronic lymphocytic leukemia, breast cancer and uveal melanoma tumor
      samples, we show that hundreds of cryptic 3' splice sites (3'SSs) are used in
      cancers with SF3B1 mutations. We define the necessary sequence context for the
      observed cryptic 3' SSs and propose that cryptic 3'SS selection is a result of
      SF3B1 mutations causing a shift in the sterically protected region downstream of
      the branch point. While most cryptic 3'SSs are present at low frequency (<10%)
      relative to nearby canonical 3'SSs, we identified ten genes that preferred out-of
      frame cryptic 3'SSs. We show that cancers with mutations in the SF3B1 HEAT 5-9
      repeats use cryptic 3'SSs downstream of the branch point and provide both a
      mechanistic model consistent with published experimental data and affected
      targets that will guide further research into the oncogenic effects of SF3B1
      mutation. 

PMID- 25768985
TI  - Rapid fluorescence-based measurement of toxicity in anaerobic digestion.
AB  - A rapid fluorescence measurement based on resazurin reduction was developed and
      applied for the detection of toxicants/inhibitors to anaerobic digestion
      metabolism. By initially using a pure facultative anaerobic strain, Enterococcus
      faecalis as a model organism, this technique proved to be fast and sensitive when
      detecting the model toxicant, pentachlorophenol (PCP). The technique revealed
      significant metabolic changes in Enterococcus faecalis with a PCP spike ranging
      from 0.05 to 100 mg/L, and could detect PCP's toxicity to E. faecalis at a
      concentration of only 0.05 mg/L in 8 min. Furthermore, by extending this
      technique to a mixed anaerobic sludge, not only could the effect of 0.05-100 mg/L
      PCP be determined on anaerobic digestion metabolism within 10 min, but also its
      rate of biogas production. These results suggest that a resazurin-based
      fluorescence measurement can potentially be incorporated into a microfluidic
      system to develop a biosensor for the real-time monitoring, control and early
      warning of toxicant/inhibitor loads in the influent to an anaerobic digestion
      system.

PMID- 25768986
TI  - Numerical simulation of bubble induced shear in membrane bioreactors: effects of
      mixed liquor rheology and membrane configuration.
AB  - A CFD model, incorporating an empirically determined rheology model and a porous
      media model, was developed to simulate bubble induced surface shear in membrane
      bioreactors configured with hollow fibre membranes with outer diameters ranging
      from 1.3 to 2.4 mm, arranged in vertically orientated modules with packing
      density from 200 to 560 m(2)/m(3). The rheology model was developed for mixed
      liquor suspended solids (MLSS) concentrations of 3 to 16 gL(-1) in the presence
      and absence of coagulant (generated by addition of a ferrous salt) for shear
      rates ranging from 0 to 500 s(-1). Experimentally determined particle relaxation
      times for the biological flocs in the mixed liquor, both in the absence and
      presence of iron, were negligible, consistent with an environment where positive
      buoyancy forces were greater than negative settling forces thereby allowing the
      sludge mixture to be modelled as a single continuous phase. The non-Newtonian
      behaviour of the mixed liquor was incorporated into the CFD simulations using an
      Ostwald-de Waele rheology model. Interactions between mixed liquor and hollow
      fibre membranes of different fibre size and packing density were described using
      a porous media model that was calibrated by empirical measurement of inertial
      loss coefficients over a range of viscosities (0.8 * 10(-3) to 2.1 * 10(-3) Pa.s)
      and velocities (0 to 0.35 m/s) typically encountered in full scale MBRs.
      Experimental results indicated that addition of iron salts resulted in an
      increase in MLSS and sludge viscosity. Shear stress is affected by both velocity
      and viscosity. The increase in sludge viscosity resulted in an increase in
      resistance to flow through the hollow fibre membrane bundles and, as a result,
      decreased the liquid flow velocities. CFD simulations provided insight on the
      effects of point of coagulant addition and MLSS concentration on bubble-induced
      shear over a range of industrially relevant conditions. A 12% increase in shear
      stress was observed when ferrous salts were added to the membrane filtration zone
      compared to addition to the primary anoxic zone. The presence of iron salts also
      improved the distribution of shear stress especially at the lower zone of the
      membrane module. The CFD models developed here were validated using Particle
      Image Velocimetry (PIV) with the average difference between simulated liquid
      velocities and PIV measured velocities found to be 5.5%.

PMID- 25768987
TI  - Principles for scaling of distributed direct potable water reuse systems: a
      modeling study.
AB  - Scaling of direct potable water reuse (DPR) systems involves tradeoffs of
      treatment facility economy-of-scale, versus cost and energy of conveyance
      including energy for upgradient distribution of treated water, and retention of
      wastewater thermal energy. In this study, a generalized model of the cost of DPR
      as a function of treatment plant scale, assuming futuristic, optimized conveyance
      networks, was constructed for purposes of developing design principles. Fractal
      landscapes representing flat, hilly, and mountainous topographies were simulated,
      with urban, suburban, and rural housing distributions placed by modified
      preferential growth algorithm. Treatment plants were allocated by agglomerative
      hierarchical clustering, networked to buildings by minimum spanning tree.
      Simulations assume advanced oxidation-based DPR system design, with 20-year
      design life and capability to mineralize chemical oxygen demand below normal
      detection limits, allowing implementation in regions where disposal of
      concentrate containing hormones and antiscalants is not practical. Results
      indicate that total DPR capital and O&M costs in rural areas, where systems that
      return nutrients to the land may be more appropriate, are high. However, costs in
      urban/suburban areas are competitive with current water/wastewater service costs
      at scales of ca. one plant per 10,000 residences. This size is relatively small,
      and costs do not increase significantly until plant service areas fall below 100
      to 1000 homes. Based on these results, distributed DPR systems are recommended
      for consideration for urban/suburban water and wastewater system capacity
      expansion projects. 

PMID- 25768988
TI  - Effects of triclosan, diclofenac, and nonylphenol on mesophilic and thermophilic
      methanogenic activity and on the methanogenic communities.
AB  - In this study, a toxicity assay using a mesophilic wastewater treatment plant
      sludge-based (SI) and a thermophilic manure-based inoculum (MI), under different
      biomass concentrations was performed to define the effects of diclofenac (DCF),
      triclosan (TCS), and nonylphenol (NP) on anaerobic digestion (AD) process.
      Additionally, the influence of DCF, TCS, and NP on the relative abundance of the
      methanogenic populations was investigated. Results obtained demonstrated that, in
      terms of methane production, SI inoculum was more resistant to the toxicity
      effect of DCF, TCS, and NP, compared to the MI inoculum. The IC50 values were
      546, 35, and 363 mg L(-1) for SI inoculum and 481, 32, and 74 mg L(-1) for MI
      inoculum for DCF, TCS, and NP, respectively. For both inocula, higher biomass
      concentrations reduced the toxic effect of TCS (higher methane production up to
      64%), contrary to DCF, where higher biomass loads decreased methane yield up to
      31%. Fluorescence in situ hybridization analysis showed that hydrogenotrophic
      methanogens were more resistant to the inhibitory effect of DCF, TCS, and NP
      compared to aceticlastic methanogens.

PMID- 25768989
TI  - A new method of utilizing rice husk: consecutively preparing D-xylose, organosolv
      lignin, ethanol and amorphous superfine silica.
AB  - Rice husk is an abundant agricultural by-product with the annual output of 120
      and 40 million tons in the world and China, respectively. The common disposal
      method of rice husk in China has caused the pollution. This manuscript deals with
      a new method of comprehensively utilizing rice husk, by which hazardous materials
      are avoided to release. 100.3, 219.4, 50.1 and 170.5 g of D-xylose, organosolv
      lignin, ethanol and superfine silica are consecutively prepared from 1000 g of
      rice husk. This new method is helpful to resolving the problem of pollution and
      waste aroused by rice husk.

PMID- 25768990
TI  - Treatment of a simulated textile wastewater in a sequencing batch reactor (SBR)
      with addition of a low-cost adsorbent.
AB  - Color removal from textile wastewaters, at a low-cost and consistent technology,
      is even today a challenge. Simultaneous biological treatment and adsorption is a
      known alternative to the treatment of wastewaters containing biodegradable and
      non-biodegradable contaminants. The present work aims at evaluating the
      treatability of a simulated textile wastewater by simultaneously combining
      biological treatment and adsorption in a SBR (sequencing batch reactor), but
      using a low-cost adsorbent, instead of a commercial one. The selected adsorbent
      was a metal hydroxide sludge (WS) from an electroplating industry. Direct Blue 85
      dye (DB) was used in the preparation of the synthetic wastewater. Firstly,
      adsorption kinetics and equilibrium were studied, in respect to many factors
      (temperature, pH, WS dosage and presence of salts and dyeing auxiliary chemicals
      in the aqueous media). At 25  degrees C and pH 4, 7 and 10, maximum DB adsorption
      capacities in aqueous solution were 600, 339 and 98.7 mg/g, respectively. These
      values are quite considerable, compared to other reported in literature, but
      proved to be significantly reduced by the presence of dyeing auxiliary chemicals
      in the wastewater. The simulated textile wastewater treatment in SBR led to BOD5
      removals of 53-79%, but color removal was rather limited (10-18%). The
      performance was significantly enhanced by the addition of WS, with BOD5 removals
      above 91% and average color removals of 60-69%.

PMID- 25768991
TI  - Brentuximab vedotin as single agent in refractory or relapsed CD30-positive
      Hodgkin lymphoma: the French Name Patient Program experience in 241 patients.

PMID- 25768992
TI  - Subcutaneous rituximab and chemotherapy achieves similar overall response rates
      to intravenous rituximab in first-line follicular lymphoma: efficacy and safety
      results of the phase III SABRINA study.

PMID- 25768993
TI  - Increased rituximab (R) doses eliminate increased risk and improve outcome of
      elderly male patients with aggressive CD20+ B-cell lymphomas: the SEXIE-R-CHOP-14
      trial of the DSHNHL.

PMID- 25768994
TI  - Phase 3 study of frontline rituximab, cyclophosphamide, doxorubicin, and
      prednisone plus vincristine (R-CHOP) or bortezomib (VR-CAP) in transplantation
      unsuitable mantle cell lymphoma (MCL) patients.

PMID- 25768995
TI  - Brentuximab vedotin for Hodgkin lymphoma who had failed allogeneic stem cell
      transplantation: a multicenter retrospective study.

PMID- 25768996
TI  - Final analysis of a randomized phase II study with prednisone, vinblastine,
      doxorubicin, and gemcitabine in patients with early unfavorable Hodgkin lymphoma
      PVAG-14 pilot.

PMID- 25768997
TI  - Preliminary results of a phase II randomized study (ROMULUS) of polatuzumab
      vedotin or pinatuzumab vedotin plus rituximab in patients with
      relapsed/refractory non-Hodgkin lymphoma (NHL).

PMID- 25768998
TI  - Phase I study of ABT-199 (GDC-0199) in patients with relapsed/refractory non
      Hodgkin lymphoma: responses observed in diffuse large B-cell (DLBCL) and
      follicular lymphoma (FL) at higher cohort doses.

PMID- 25768999
TI  - Safety and efficacy of brentuximab vedotin (SGN-35) in Hodgkin lymphoma patients
      undergoing reduced intensity allogeneic stem cell transplant following a relapse
      after autologous transplant.

PMID- 25769000
TI  - Highlights in lymphoma from the 2014 European Hematology Association Congress.

PMID- 25769002
TI  - Increased risk of acute coronary syndrome among leptospirosis patients: A
      nationwide cohort analysis.
AB  - BACKGROUND: Studies on the association between leptospirosis and acute coronary
      syndrome (ACS) are lacking. Therefore, this study identifies the effects of
      leptospirosis on the risks of developing ACS with a nationwide retrospective
      cohort study. METHODS: We identified adult patients aged >=20 years who were
      newly diagnosed with leptospirosis. We also randomly selected a comparison cohort
      from the general population by using a propensity score matching method. We
      analyzed the risks of ACS by using Cox proportional hazard regression models.
      RESULTS: Among the 23.74 million people in the cohort, 3690 patients with
      leptospirosis (68% men, mean age of 52.2 years) and 3690 controls were followed
      for 13,677 and 15,652 person-years, respectively. The overall incidence of ACS
      was higher in the leptospirosis cohort than in the nonleptospirosis cohort (4.68
      vs 3.71 per 1000 person-years), with a hazard ratio (HR) of 1.69 (95% confidence
      interval [CI]=1.12-2.56). Men exhibited a 1.88-fold greater HR of ACS than women
      did (95% CI=1.20-2.94). The risk of developing ACS was highest for leptospirosis
      patients aged >=65 years (HR=7, 51% CI=4.35-12.9) compared with patients aged
      <=49 years. CONCLUSION: Leptospirosis is not a previously identified risk factor
      for ACS. The findings of this nationwide retrospective cohort study indicate that
      leptospirosis may become an independent risk factor for ACS. Future research to
      investigate the mechanism is warranted.

PMID- 25769001
TI  - Mutational dichotomy in desmoplastic malignant melanoma corroborated by multigene
      panel analysis.
AB  - Desmoplastic malignant melanoma is a distinct melanoma entity histologically
      subtyped into mixed and pure forms due to significantly reduced lymph node
      metastases in the pure form. Recent reports investigating common actionable
      driver mutations have demonstrated a lack of BRAF, NRAS, and KIT mutation in pure
      desmoplastic melanoma. In search for alternative driver mutations next generation
      amplicon sequencing for hotspot mutations in 50 genes cardinal to tumorigenesis
      was performed and in addition the RET G691S polymorphism was investigated. Data
      from 21 desmoplastic melanomas (12 pure and 9 mixed) were retrieved. Pure
      desmoplastic melanomas were either devoid of mutations (50%) or displayed
      mutations in tumor suppressor genes (TP53, CDKN2A, and SMAD4) singularly or in
      combination with the exception of a PIK3CA double-mutation lacking established
      biological relevance. Mixed desmoplastic melanomas on the contrary were
      frequently mutated (89%), and 67% exhibited activating mutations similar to
      common-type cutaneous malignant melanomas (BRAF, NRAS, FGFR2, and ERBB2).
      Separate analysis of morphologically heterogeneous tumor areas in four mixed
      desmoplastic malignant melanomas displayed no difference in mutation status and
      RET G691 status. GNAQ and GNA11, two oncogenes in BRAF and NRAS wild-type uveal
      melanomas, were not mutated in our cohort. The RET G691S polymorphism was found
      in 25% of pure and 38% of mixed desmoplastic melanomas. Apart from RET G691S our
      findings demonstrate absence of activating driver mutations in pure desmoplastic
      melanoma beyond previously investigated oncogenes (BRAF, NRAS, and KIT). The
      findings underline the therapeutic dichotomy of mixed versus pure desmoplastic
      melanoma with regard to activating mutations primarily of the mitogen-activated
      protein kinase pathway. 

PMID- 25769003
TI  - High dose and long-term statin therapy accelerate coronary artery calcification.
AB  - BACKGROUND: In randomized clinical trials statins and placebo treated patients
      showed the same degree of coronary artery calcium (CAC) progression. We
      reanalyzed data from two clinical trials to further investigate the time and dose
      dependent effects of statins on CAC. Additionally, we investigated whether CAC
      progression was associated with incident cardiovascular events. METHODS AND
      RESULTS: Data were pooled from two clinical trials: St. Francis Heart Study
      (SFHS) (419 and 432 patients treated with placebo and 20 mg atorvastatin daily,
      respectively) and EBEAT Study (164 and 179 patients respectively treated with 10
      mg and 80 mg atorvastatin daily). CAC scores were assessed at baseline, 2 years
      and 4-6 years in SFHS; in EBEAT they were measured at baseline and 12 months.
      After a short-term follow-up (12 to 24 months) placebo and low dose atorvastatin
      showed a similar CAC increase, although 80 mg/daily atorvastatin increased CAC an
      additional 12-14% over placebo (p<0.001). In the long-term, atorvastatin caused a
      greater progression of CAC compared to placebo (additional 1.1%, p=0.04). In SFHS
      42 cardiovascular events occurred after the second CT scan. The baseline and
      progression of CAC were greater in patients with events. However, only baseline
      CAC and family history of premature cardiovascular disease but not CAC
      progression were independent predictors of events. CONCLUSIONS: Despite a greater
      CAC increase with high dose and long-term statin therapy, events did not occur
      more frequently in statin treated patients. This suggests that CAC growth under
      treatment with statins represents plaque repair rather than continuing plaque
      expansion.

PMID- 25769005
TI  - Relation of growth differentiation factor-15 with CHA2DS2-VASc score in Chinese
      patients with non-valvular atrial fibrillation.

PMID- 25769004
TI  - A new approach to test validity and clinical usefulness of the 2013 ACC/AHA
      guideline on statin therapy: A population-based study.
AB  - BACKGROUND: The ACC/AHA released a new guideline on the assessment of
      cardiovascular risk and management of hypercholesterolemia that some controversy
      exists concerning its usefulness. We examined the clinical usefulness of this
      guideline in a high incidence population using novel measures. METHODS: First, we
      validated the new risk equation in a cohort of 2372 men and 2781 women aged 40-75
      years. Then, high risk individuals for cardiovascular diseases (CVDs) were
      identified according to the ACC/AHA guideline at baseline (as a predictor) and
      CVD outcomes were detected during a 10-year follow-up. Discrimination of the
      guideline was quantified and the quality of decisions was evaluated by Net
      Benefit Fraction index considering the harm, for false-positive, and benefit, for
      true-positive predictions. Finally, net number needed to treat (NNT) for statin
      was estimated, using test tradeoff index, in diabetic and non-diabetic subjects.
      RESULTS: During follow-up, 726 CVD events including 298 hard CVDs occurred. The
      equation overestimated the risk by 57% in men and 48% in women. Based on the
      guideline, 73% of men and 44% of women were eligible for statin therapy. The
      lowest sensitivity was detected for intensive treatment in non-diabetic subgroups
      (82% in men and 41% in women; corresponding specificity, 52% and 90%
      respectively). The guideline had a significant net benefit for both moderate and
      intensive treatment, which resulted in estimated NNTs ranged 5-55; however, net
      benefit of intensive therapy was uncertain in non-diabetic women. CONCLUSIONS: We
      objectively showed that the ACC/AHA recommendations could be useful in our
      population but with some overtreatment in women.

PMID- 25769006
TI  - From cardiac mitochondrial dysfunction to clinical arrhythmias.

PMID- 25769007
TI  - Myotonic dystrophy and the heart: A systematic review of evaluation and
      management.
AB  - Myotonic dystrophy (MD) is a multisystem, autosomal dominant disorder best known
      for its skeletal muscle manifestations. Cardiac manifestations arise as a result
      of myocardial fatty infiltration, degeneration and fibrosis and present most
      commonly as arrhythmias or conduction disturbances. Guidelines regarding the
      optimal cardiac management of patients with MD are lacking. The present article
      provides a summary of the pathophysiology of cardiac problems in patients with MD
      and provides a practical approach to contemporary cardiac monitoring and
      management of these patients with a focus on the prevention of complications
      related to conduction disturbances and arrhythmias. METHODS: A literature search
      was performed using PubMed and Medline. The keywords used in the search included
      "myotonic dystrophy", "cardiac manifestations", "heart", "arrhythmia",
      "pacemaker" and "defibrillator", all terms were used in combination. In addition,
      "myotonic dystrophy" was searched in conjunction with "electrophysiology",
      "electrocardiogram", "echocardiograph", "signal averaged electrocardiograph",
      "magnetic resonance imaging" and "exercise stress testing". The titles of all the
      articles revealed by the search were screened for relevance. The abstracts of
      relevant titles were read and those articles which concerned the cardiac
      manifestations of myotonic dystrophy or the investigation and management of
      cardiac manifestations underwent a full manuscript review.

PMID- 25769008
TI  - Maximal heart rate in young adults: A fixed 188 bpm outperforms values predicted
      by a classical age-based equation.

PMID- 25769009
TI  - Efficiency study of a big volume well type NaI(Tl) detector by point and
      voluminous sources and Monte-Carlo simulation.
AB  - The activity of environmental samples is usually measured by high resolution HPGe
      gamma spectrometers. In this work a set-up with a 9in.x9in. NaI well-detector
      with 3in. thickness and a 3in.*3in. plug detector in a 15-cm-thick lead shielding
      is considered as an alternative (Hansman, 2014). In spite of its much poorer
      resolution, it requires shorter measurement times and may possibly give better
      detection limits. In order to determine the U-238, Th-232, and K-40 content in
      the samples by this NaI(Tl) detector, the corresponding photopeak efficiencies
      must be known. These efficiencies can be found for certain source matrix and
      geometry by Geant4 simulation. We found discrepancy between simulated and
      experimental efficiencies of 5-50%, which can be mainly due to effects of light
      collection within the detector volume, an effect which was not taken into account
      by simulations. The influence of random coincidence summing on detection
      efficiency for radionuclide activities in the range 130-4000Bq, was negligible.
      This paper describes also, how the efficiency in the detector depends on the
      position of the radioactive point source. To avoid large dead time, relatively
      weak Mn-54, Co-60 and Na-22 point sources of a few kBq were used. Results for
      single gamma lines and also for coincidence summing gamma lines are presented. 

PMID- 25769010
TI  - The optically stimulated luminescence (OSL) properties of LiF:Mg,TI, Li2B4O7:CU,
      CaSO4:Tm, and CaF2:MN thermoluminescent (TL) materials.
AB  - This paper reports on an investigation into the optically stimulated luminescence
      (OSL) properties of several known thermoluminescent materials, namely LiF:Mg,Ti,
      Li2B4O7:Cu, CaSO4:Tm, and CaF2:Mn. Samples were irradiated to air doses of 15mGy,
      150mGy and 1.5Gy and analyzed using a commercially available OSL reader system to
      determine their luminescence response to continuous blue and infrared light (IR)
      excitation, centered at 470nm and 830nm wavelengths, respectively. CaF2:Mn did
      not show an OSL response with either IR or blue light stimulation. Li2B4O7:Cu and
      LiF:Mg,Ti demonstrated relatively weak OSL signals only under blue light
      excitation. CaSO4:Tm exhibited OSL under both IR and blue light stimulation at
      sensitivities roughly one order of magnitude less than the OSL response of alpha
      Al2O3:C under the same conditions. 

PMID- 25769011
TI  - Quantification of bindings of organometallic ruthenium complexes to GSTpi by mass
      spectrometry.
AB  - Electrospray ionization mass spectrometry (ESI-MS) has been widely used to
      identify binding sites of metal complexes to proteins. However, the MS
      quantification of the metal-protein coordination remains a challenge. We have
      recently demonstrated by ESI-MS analysis that organometallic ruthenium complexes
      [(eta(6)-arene)Ru(en)Cl](+) (arene=p-cymene (1), biphenyl (2) or 9,10
      dihydrophenanthrene (3); en=ethylenediamine) bound to human glutathione-S
      transferase pi (GSTpi) at Cys15 and Cys48 within the G-site, and Cys102 and Met92
      on the interface of the GSTpi dimer, showing inhibitory potency against the
      enzyme (J. Inorg. Biochem., 128 (2013) 77-84). Herein, we developed a mass
      spectrometric method to quantify the binding stoichiometry of the three complexes
      to GSTpi. The differences in signal intensities of the heavy-labelled peptides
      produced by tryptic digestion of the ruthenated GSTpi complexes and the
      respective light-labelled peptides in the tryptic digest of equimolar GSTpi were
      used to calculate the binding stoichiometry at specific residues. The results
      indicated that the pre-complexation of GSTpi with its substrate GSH significantly
      reduced the bindings of the ruthenium complexes at Met92 and Cys102, but had
      little impact on the bindings at Cys15 and Cys48. As the inhibitory activities of
      the ruthenium complexes against GSTpi are similar to those against GSTpi in
      complexation with GSH, these results suggest that the inhibition of the ruthenium
      complexes on GSTpi is attributed to the ruthenation at Cys15 and Cys48. The
      present work provides not only insights into the understanding on the inhibitory
      mechanism of ruthenium complexes GSTpi, but also a general method for
      quantitative characterization of metal-protein interactions. 

PMID- 25769012
TI  - Total synthesis of sphingofungin F by orthoamide-type overman rearrangement of an
      unsaturated ester.
AB  - The total synthesis of sphingofungin F through the Overman rearrangement of an
      unsaturated ester, which is known to be an unsuitable substrate under standard
      conditions due to the competitive aza-Michael reaction, is described. The
      developed conditions enabled the ester to be compatible with the original Overman
      rearrangement, providing quick access to alpha,alpha-disubstituted amino acids by
      minimizing extra protecting group manipulations and redox reactions. 

PMID- 25769014
TI  - Characterization of the N-terminal heterogeneities of monoclonal antibodies using
      in-gel charge derivatization of alpha-amines and LC-MS/MS.
AB  - The bioproduction of recombinant monoclonal antibodies results in complex
      mixtures of a main isoform and numerous macro- and microvariants. Monoclonal
      antibodies therefore present different levels of heterogeneities ranging from
      primary sequence variants to post-translational modifications. Among these
      heterogeneities, the truncation and fragmentation of the primary amino-acid
      sequence result in shorter or cleaved polypeptide chains while the incomplete
      processing of the signal peptide produces N-terminal elongated polypeptide
      chains. Here, we present an in-gel protein N-terminal chemical derivatization
      method using (N-succinimidyloxycarbonylmethyl)-tris(2,4,6
      trimethoxyphenyl)phosphonium bromide (TMPP). This chemical tag enhances the
      detection by mass spectrometry of the N-terminal positions of proteins and allows
      their unambiguous assignment without altering the identification of internal
      digestion peptides. This method adds just one step to the classical peptide
      mapping workflow. Using this in-gel N-TOP (N-terminal oriented proteomics)
      strategy, the N-terminal sequence heterogeneities of several monoclonal
      antibodies, among which are minor unexpected proteoforms, were successfully
      detected and characterized. 

PMID- 25769013
TI  - Differential intensity-dependent effects of magnetic stimulation on the longest
      neurites and shorter dendrites in neuroscreen-1 cells.
AB  - OBJECTIVE: Magnetic stimulation (MS) is a potential treatment for
      neuropsychiatric disorders. This study investigates whether MS-regulated neuronal
      activity can translate to specific changes in neuronal arborization and thus
      regulate synaptic activity and function. APPROACH: To test our hypotheses, we
      examined the effects of MS on neurite growth of neuroscreen-1 (NS-1) cells over
      the pulse frequencies of 1, 5 and 10 Hz at field intensities controlled via
      machine output (MO). Cells were treated with either 30% or 40% MO. Due to the
      nature of circular MS coils, the center region of the gridded coverslip (zone 1)
      received minimal (~5%) electromagnetic current density while the remaining area
      (zone 2) received maximal (~95%) current density. Plated NS-1 cells were exposed
      to MS twice per day for three days and then evaluated for length and number of
      neurites and expression of brain-derived neurotrophic factor (BDNF). MAIN
      RESULTS: We show that MS dramatically affects the growth of the longest neurites
      (axon-like) but does not significantly affect the growth of shorter neurites
      (dendrite-like). Also, MS-induced changes in the longest neurite growth were most
      evident in zone 1, but not in zone 2. MS effects were intensity-dependent and
      were most evident in bolstering longest neurite outgrowth, best seen in the 10 Hz
      MS group. Furthermore, we found that MS-increased BDNF expression and secretion
      was also frequency-dependent. Taken together, our results show that MS exerts
      distinct effects when different frequencies and intensities are applied to the
      neuritic compartments (longest neurite versus shorter dendrite(s)) of NS-1 cells.
      SIGNIFICANCE: These findings support the concept that MS increases BDNF
      expression and signaling, which sculpts longest neurite arborization and
      connectivity by which neuronal activity is regulated. Understanding the
      mechanisms underlying MS is crucial for efficiently incorporating its use into
      potential therapeutic strategies.

PMID- 25769015
TI  - Cystargolides, 20S Proteasome Inhibitors Isolated from Kitasatospora cystarginea.
AB  - Two novel beta-lactone-containing natural products, cystargolides A (1) and B
      (2), were isolated from the actinomycete Kitasatospora cystarginea. The
      production of these two natural products was highlighted using a methodology
      associating liquid chromatography-high-resolution mass spectrometry (LC-HRMS)
      analysis and the statistical analysis tool principal component analysis (PCA).
      Their structures were elucidated by interpretation of NMR experiments and tandem
      mass spectrometry. The absolute configurations of the amino acid residues were
      determined using Marfey's method, and the relative configurations of the beta
      lactone substituents were determined on the basis of the vicinal (3)J(HH)
      coupling value. Due to the presence of the beta-lactone, 1 and 2 were evaluated
      for their ability to inhibit the human 20S proteasome. 1 and 2 both inhibited the
      20S proteasome in vitro with IC50 values of 0.35 and 0.93 MUM, respectively.

PMID- 25769016
TI  - Correction for a bio-based alternative to the digylcidyl ether of bisphenol a
      with controlled materials properties.

PMID- 25769017
TI  - An in vitro study on the effect of an oscillating stripping method on enamel
      roughness.
AB  - BACKGROUND: The aim of the present study was to assess the changes in enamel
      roughness parameters before and after stripping with an oscillating diamond strip
      system. METHODS: Sound premolars extracted for orthodontic reasons were embedded
      up to their cervical area in a polyvinylsiloxane putty, creating four groups of
      four teeth with three interproximal areas each (mesial/distal). The same regions
      of interproximal enamel surfaces were studied by 3D optical interferometric
      profilometry before and after stripping with the Ortho-Strips system (Intensiv
      Dental SA, Montagnola, Switzerland) (n teeth = 16, n contact points = 12, n sites
      measured = 24). The roughness parameters tested were the amplitude parameters Sa
      and Sz, the hybrid parameter Sdr, and the functional parameters Sci and Svi. The
      parameter differences (DeltaSa, DeltaSz, DeltaSdr, DeltaSci, DeltaSvi) were
      calculated per region and statistically analyzed by one-sample Mann-Whitney rank
      sum test (a = 0.05). RESULTS: High statistically significant differences were
      found in DeltaSa, DeltaSz, and DeltaSvi median values (0.453, 3.870, and 0.040
      MUm, respectively); a significant difference in DeltaSdr median value (1.514%);
      and no statistically significant difference in DeltaSci (0.110 median value).
      CONCLUSIONS: Under the conditions of the present study, the Ortho-Strips system
      seems to significantly increase the amplitude parameters Sa and Sz; the hybrid
      parameter Sdr, associated with the developed interfacial area ratio; and the
      functional parameter Svi, which depicts the volume of the deepest valleys. Under
      the conditions of the present study, the Ortho-Strips seems to significantly
      increase four of five measured roughness parameters.

PMID- 25769018
TI  - Stereochemical determination of the leupyrrins and total synthesis of leupyrrin
      A1.
AB  - The stereochemical determination of the potent antifungal agents leupyrrin A1 and
      B1 and the total synthesis of leupyrrin A1 are reported. The relative and
      absolute configuration was determined by a combination of high field NMR studies,
      molecular modeling, and chemical derivatization. The expedient total synthesis
      involves a one-pot sequential Zr-mediated oxidative diyne
      cyclization/regioselective opening sequence for preparation of the unique
      dihydrofuran ring, a highly stereoselective one-pot approach to the
      butyrolactone, a challenging sp(2)-sp(3) Suzuki coupling and a high-yielding
      Shiina macrolactonization. 

PMID- 25769020
TI  - The Effect of Noise on the Relationship Between Auditory Working Memory and
      Comprehension in School-Age Children.
AB  - PURPOSE: The objectives of the current study were to examine the effect of noise
      (-5 dB SNR) on auditory comprehension and to examine its relationship with
      working memory. It was hypothesized that noise has a negative impact on
      information processing, auditory working memory, and comprehension. METHOD:
      Children with normal hearing between the ages of 8 and 10 years were administered
      working memory and comprehension tasks in quiet and noise. The comprehension
      measure comprised 5 domains: main idea, details, reasoning, vocabulary, and
      understanding messages. RESULTS: Performance on auditory working memory and
      comprehension tasks were significantly poorer in noise than in quiet. The
      reasoning, details, understanding, and vocabulary subtests were particularly
      affected in noise (p < .05). The relationship between auditory working memory and
      comprehension was stronger in noise than in quiet, suggesting an increased
      contribution of working memory. CONCLUSIONS: These data suggest that school-age
      children's auditory working memory and comprehension are negatively affected by
      noise. Performance on comprehension tasks in noise is strongly related to demands
      placed on working memory, supporting the theory that degrading listening
      conditions draws resources away from the primary task.

PMID- 25769019
TI  - Full Viral Suppression, Low-Level Viremia, and Quantifiable Plasma HIV-RNA at the
      End of Pregnancy in HIV-Infected Women on Antiretroviral Treatment.
AB  - There is limited information on full viral suppression and low-level HIV-RNA
      viremia in HIV-infected women at the end of pregnancy. We investigated HIV-RNA
      levels close to delivery in women on antiretroviral treatment in order to define
      rates of complete suppression, low-level viremia, and quantifiable HIV-RNA,
      exploring as potential determinants some clinical and viroimmunological
      variables. Plasma samples from a national study in Italy, collected between 2003
      and 2012, were used. According to plasma HIV-RNA levels, three groups were
      defined: full suppression (target not detected), low-level viremia (target
      detected but <37 copies/ml), and quantifiable HIV-RNA (>=37 copies/ml).
      Multivariable logistic regression was used to define determinants of full viral
      suppression and of quantifiable HIV-RNA. Among 107 women evaluated at a median
      gestational age of 35 weeks, 90 (84.1%) had HIV-RNA <37 copies/ml. Most of them
      (59/90, 65.6%) had full suppression, with the remaining (31/90, 34.4%) showing
      low-level viremia (median: 11.9 copies/ml; IQR 7.4-16.3). Among the 17 women with
      quantifiable viral load, median HIV-RNA was 109 copies/ml (IQR 46-251), with only
      one case showing resistance (mutation M184V; rate: 9.1%). In multivariable
      analyses, women with higher baseline HIV-RNA levels and with hepatitis C virus
      (HCV) coinfection were significantly more likely to have quantifiable HIV-RNA in
      late pregnancy. Full viral suppression was significantly more likely with
      nonnucleoside reverse transcriptase inhibitor (NNRTI)-based regimens and
      significantly less likely with higher HIV-RNA in early pregnancy. No cases of HIV
      transmission occurred. In conclusion, HIV-infected pregnant women showed a high
      rate of viral suppression and a low resistance rate before delivery. In most
      cases no target HIV-RNA was detected in plasma, suggesting a low risk of
      subsequent virological rebound and development of resistance. Women with high
      levels of HIV-RNA in early pregnancy and those who have concomitant HCV infection
      should be considered at higher risk of having quantifiable HIV-RNA at the end of
      pregnancy.

PMID- 25769021
TI  - Novel metal-organic framework with tunable fluorescence property: supramolecular
      signaling platform for polynitrophenolics.
AB  - With the aid of a rotational C3-symmetric tricarboxytriphenylamine based ligand,
      a new Cd-MOF was synthesized and characterized by various spectroscopic
      techniques as well as by single-crystal X-ray diffraction analysis. The
      structural investigation of the crystalline Cd-MOF complex revealed the existence
      of unique three symmetry independent coordination environments of Cd(ii) ions
      with common octahedral and pentagonal bipyramidal geometries. Small cavities with
      dimensions 6.40 A * 6.41 A were present in the crystal system. The tunable
      fluorescence property of the complex was explored to detect selectively
      polynitrophenol based explosive materials in the presence of other nitro
      explosives such as RDX, HMX, TNT and so on. Thermogravimetric analysis and powder
      X-ray diffraction data support the high thermal stability and crystallinity of
      the complex. 

PMID- 25769022
TI  - Development of orthogonally protected hypusine for solid-phase peptide synthesis.
AB  - An orthogonally protected hypusine reagent was developed for solid-phase
      synthesis of hypusinated peptides using the Fmoc/t-Bu protection strategy. The
      reagent was synthesized in an overall yield of 27% after seven steps from Cbz-Lys
      OBzl and (R)-3-hydroxypyrrolidin-2-one. The side-chain protecting groups (Boc and
      t-Bu) are fully compatible with standard Fmoc chemistry and can be readily
      removed during the peptide cleavage step. The utility of the reagent was
      demonstrated by solid-phase synthesis of hypusinated peptides. 

PMID- 25769023
TI  - Associations between work environment and psychological distress after a
      workplace terror attack: the importance of role expectations, predictability and
      leader support.
AB  - Experiencing terrorism is associated with high levels of psychological distress
      among survivors. The aim of the present study was to examine whether work
      environmental factors such as role clarity and predictability, role conflicts,
      and leader support may protect against elevated levels of psychological distress
      after a workplace terrorist attack. Data from approximately 1800 ministerial
      employees were collected ten months after the 2011 Oslo bombing attack which
      targeted the Norwegian ministries. The results show that after a traumatic event,
      lower role conflicts, higher role clarity, higher predictability, and higher
      leader support were independently associated with lower psychological distress.
      These findings suggest that the workplace environment may be a facilitator of
      employees' mental health after stressful events. 

PMID- 25769024
TI  - Lateral manipulation of atomic vacancies in ultrathin insulating films.
AB  - During the last 20 years, using scanning tunneling microscopy (STM) and atomic
      force microscopy, scientists have successfully achieved vertical and lateral
      repositioning of individual atoms on and in different types of surfaces. Such
      atom manipulation allows the bottom-up assembly of novel nanostructures that can
      otherwise not be fabricated. It is therefore surprising that controlled
      repositioning of virtual atoms, i.e., atomic vacancies, across atomic lattices
      has not yet been achieved experimentally. Here we use STM at liquid helium
      temperature (4.5 K) to create individual Cl vacancies and subsequently to
      laterally manipulate them across the surface of ultrathin sodium chloride films.
      This allows monitoring the interactions between two neighboring vacancies with
      different separations. Our findings are corroborated by density functional theory
      calculations and STM image simulations. The lateral manipulation of atomic
      vacancies opens up a new playground for the investigation of fundamental physical
      properties of vacancy nanostructures of any size and shape and their coupling
      with the supporting substrate, and of the interaction of various deposits with
      charged vacancies. 

PMID- 25769025
TI  - HP1beta is a biomarker for breast cancer prognosis and PARP inhibitor therapy.
AB  - Members of the heterochromatin protein 1 family (HP1alpha, beta and gamma) are
      mostly associated with heterochromatin and play important roles in gene
      regulation and DNA damage response. Altered expression of individual HP1 subtype
      has profound impacts on cell proliferation and tumorigenesis. We analyzed the
      expression profile of HP1 family by data mining using a published microarray data
      set coupled with retrospective immunohistochemistry analyses of archived breast
      cancer biospecimens. We found that the patient group overexpressing HP1beta mRNA
      is associated with poorly differentiated breast tumors and with a significantly
      lower survival rate. Immunohistochemical staining against HP1alpha, HP1beta and
      HP1gamma shows that respective HP1 expression level is frequently altered in
      breast cancers. 57.4-60.1% of samples examined showed high HP1beta expression and
      39.9-42.6 % of examined tumors showed no or low expression of each HP1 subtype.
      Interestingly, comparative analysis on HP1 expression profile and breast cancer
      markers revealed a positive correlation between the respective expression level
      of all three HP1 subtypes and Ki-67, a cell proliferation and well-known breast
      cancer marker. To explore the effect of individual HP1 on PARP inhibitor therapy
      for breast cancer, MCF7 breast cancer cells and individually HP1-depleted MCF7
      cells were treated with PARP inhibitor ABT-888 with or without carboplatin.
      Notably, HP1beta-knockdown cells are hypersensitive to the PARP inhibitor ABT-888
      alone and its combination with carboplatin. In summary, while increased HP1beta
      expression is associated with the poor prognosis in breast cancer, compromised
      HP1beta abundance may serve as a useful predictive marker for chemotherapy,
      including PARP inhibitors against breast cancer.

PMID- 25769027
TI  - Correction: Discovering functional modules across diverse maize transcriptomes
      using COB, the co-expression browser.

PMID- 25769026
TI  - No specific gene expression signature in human granulosa and cumulus cells for
      prediction of oocyte fertilisation and embryo implantation.
AB  - In human IVF procedures objective and reliable biomarkers of oocyte and embryo
      quality are needed in order to increase the use of single embryo transfer (SET)
      and thus prevent multiple pregnancies. During folliculogenesis there is an
      intense bi-directional communication between oocyte and follicular cells. For
      this reason gene expression profile of follicular cells could be an important
      indicator and biomarker of oocyte and embryo quality. The objective of this study
      was to identify gene expression signature(s) in human granulosa (GC) and cumulus
      (CC) cells predictive of successful embryo implantation and oocyte fertilization.
      Forty-one patients were included in the study and individual GC and CC samples
      were collected; oocytes were cultivated separately, allowing a correlation with
      IVF outcome and elective SET was performed. Gene expression analysis was
      performed using microarrays, followed by a quantitative real-time PCR validation.
      After statistical analysis of microarray data, there were no significantly
      differentially expressed genes (FDR<0,05) between non-fertilized and fertilized
      oocytes and non-implanted and implanted embryos in either of the cell type.
      Furthermore, the results of quantitative real-time PCR were in consent with
      microarray data as there were no significant differences in gene expression of
      genes selected for validation. In conclusion, we did not find biomarkers for
      prediction of oocyte fertilization and embryo implantation in IVF procedures in
      the present study. 

PMID- 25769029
TI  - Interventions for treating intrahepatic cholestasis in people with sickle cell
      disease.
AB  - BACKGROUND: Sickle cell disease is the most common hemoglobinopathy occurring
      worldwide and sickle cell intrahepatic cholestasis is a complication long
      recognized in this population. Cholestatic liver diseases are characterized by
      impaired formation or excretion (or both) of bile from the liver. There is a need
      to assess the clinical benefits and harms of the interventions used to treat
      intrahepatic cholestasis in people with sickle cell disease. OBJECTIVES: To
      assess the benefits and harms of the interventions for treating intrahepatic
      cholestasis in people with sickle cell disease. SEARCH METHODS: We searched the
      Cystic Fibrosis and Genetic Disorders Group's Haemoglobinopathies Trials
      Register, which comprises references identified from comprehensive electronic
      database searches and handsearching of relevant journals and abstract books of
      conference proceedings. We also searched the LILACS database (1982 to 7 July
      2014) and the WHO International Clinical Trials Registry Platform Search Portal
      (7 July 2014).Date of last search of the Cochrane Cystic Fibrosis and Genetic
      Disorders Group's Haemoglobinopathies Trials Register: 10 October 2014. SELECTION
      CRITERIA: We searched for published or unpublished randomised controlled trials.
      DATA COLLECTION AND ANALYSIS: Each author intended to independently extract data
      and assess the risk of bias of the trials by standard Cochrane Collaboration
      methodologies; however, no trials were included in the review. MAIN RESULTS:
      There were no randomised controlled trials identified. AUTHORS' CONCLUSIONS: This
      Cochrane Review did not identify any randomised controlled trials assessing
      interventions for treating intrahepatic cholestasis in people with sickle cell
      disease. Randomised controlled trials are needed to establish the optimum
      treatment for this condition.

PMID- 25769028
TI  - I know how you feel: the warm-altruistic personality profile and the empathic
      brain.
AB  - The ability to empathize with other people is a critical component of human
      social relationships. Empathic processing varies across the human population,
      however it is currently unclear how personality traits are associated with
      empathic processing. This study was designed to test the hypothesis that specific
      personality traits are associated with behavioral and biological indicators of
      improved empathy. Extraversion and Agreeableness are personality traits designed
      to measure individual differences in social-cognitive functioning, however each
      trait-dimension includes elements that represent interpersonal social functioning
      and elements that do not represent interpersonal social functioning. We tested
      the prediction that interpersonal elements of Extraversion (Warmth) and
      Agreeableness (Altruism) are associated with empathy and non-interpersonal
      elements of Extraversion and Agreeableness are not associated with empathy. We
      quantified empathic processing behaviorally (empathic accuracy task using video
      vignettes) and within the brain (fMRI and an emotional perspective taking task)
      in 50 healthy subjects. Converging evidence shows that highly warm and altruistic
      people are well skilled in recognizing the emotional states of other people and
      exhibit greater activity in brain regions important for empathy (temporoparietal
      junction and medial prefrontal cortex) during emotional perspective taking. A
      mediation analysis further supported the association between warm-altruistic
      personality and empathic processing; indicating that one reason why highly warm
      altruistic individuals may be skilled empathizers is that they engage the
      temporoparietal junction and medial prefrontal cortex more. Together, these
      findings advance the way the behavioral and neural basis of empathy is understood
      and demonstrates the efficacy of personality scales to measure individual
      differences in interpersonal social function. 

PMID- 25769030
TI  - Adaptive Mesh Expansion Model (AMEM) for liver segmentation from CT image.
AB  - This study proposes a novel adaptive mesh expansion model (AMEM) for liver
      segmentation from computed tomography images. The virtual deformable simplex
      model (DSM) is introduced to represent the mesh, in which the motion of each
      vertex can be easily manipulated. The balloon, edge, and gradient forces are
      combined with the binary image to construct the external force of the deformable
      model, which can rapidly drive the DSM to approach the target liver boundaries.
      Moreover, tangential and normal forces are combined with the gradient image to
      control the internal force, such that the DSM degree of smoothness can be
      precisely controlled. The triangular facet of the DSM is adaptively decomposed
      into smaller triangular components, which can significantly improve the
      segmentation accuracy of the irregularly sharp corners of the liver. The proposed
      method is evaluated on the basis of different criteria applied to 10 clinical
      data sets. Experiments demonstrate that the proposed AMEM algorithm is effective
      and robust and thus outperforms six other up-to-date algorithms. Moreover, AMEM
      can achieve a mean overlap error of 6.8% and a mean volume difference of 2.7%,
      whereas the average symmetric surface distance and the root mean square symmetric
      surface distance can reach 1.3 mm and 2.7 mm, respectively. 

PMID- 25769031
TI  - Direct identification of diverse alicyclic terpenoids in Suwannee River Fulvic
      Acid.
AB  - The chemical complexity of dissolved organic matter (DOM) obstructs our ability
      to definitively recover source compounds from within DOM, an objective which has
      the capacity to alter our understanding of carbon sequestration on a global
      scale. To advance compositional studies of DOM we have applied a previously
      published reduction method to an environmental standard, Suwannee River Fulvic
      Acid (SRFA). The reduction products, comprising 12% of the prereduced carbon,
      were then separated by comprehensive two-dimensional gas chromatography time-of
      flight mass spectrometry (GC * GC-TOF-MS). Results indicate that the majority of
      observed reduced compounds corresponded to alicyclic hydrocarbons in the size
      range C10 to C17. Cyclic terpenoids are the only biomolecule class with
      contiguous, alicyclic carbon backbones of this size. These terpenoid reduction
      products contain series offset by CH2 and exhibit great isomeric diversity,
      features previously inferred from ultrahigh resolution mass spectrometry and NMR
      studies of unreduced SRFA. Reduction of Taxodium leaf litter as a source material
      to SRFA confirmed the prevalence of terpenoids in SRFA and provided insight into
      the parent compounds that must be diagenetically modified on relatively short
      time scales. These data corroborate several recent studies that suggest alicyclic
      hydrocarbons to be important components of longer-lived DOM.

PMID- 25769032
TI  - High levels of genetic connectivity among populations of yellowtail snapper,
      Ocyurus chrysurus (Lutjanidae-Perciformes), in the western South Atlantic
      revealed through multilocus analysis.
AB  - In the present study, five loci (mitochondrial and nuclear) were sequenced to
      determine the genetic diversity, population structure, and demographic history of
      populations of the yellowtail snapper, Ocyurus chrysurus, found along the coast
      of the western South Atlantic. O. chrysurus is a lutjanid species that is
      commonly associated with coral reefs and exhibits an ample geographic
      distribution, and it can therefore be considered a good model for the
      investigation of phylogeographic patterns and genetic connectivity in marine
      environments. The results reflected a marked congruence between the mitochondrial
      and nuclear markers as well as intense gene flow among the analyzed populations,
      which represent a single genetic stock along the entire coast of Brazil between
      the states of Para and Espirito Santo. Our data also showed high levels of
      genetic diversity in the species (mainly mtDNA), as well a major historic
      population expansion, which most likely coincided with the sea level oscillations
      at the end of the Pleistocene. In addition, this species is intensively exploited
      by commercial fisheries, and data on the genetic structure of its populations
      will be essential for the development of effective conservation and management
      plans. 

PMID- 25769035
TI  - Evaluation and selection of candidate reference genes for normalization of
      quantitative RT-PCR in Withania somnifera (L.) Dunal.
AB  - Quantitative real-time PCR (qRT-PCR) is now globally used for accurate analysis
      of transcripts levels in plants. For reliable quantification of transcripts,
      identification of the best reference genes is a prerequisite in qRT-PCR analysis.
      Recently, Withania somnifera has attracted lot of attention due to its immense
      therapeutic potential. At present, biotechnological intervention for the
      improvement of this plant is being seriously pursued. In this background, it is
      important to have comprehensive studies on finding suitable reference genes for
      this high valued medicinal plant. In the present study, 11 candidate genes were
      evaluated for their expression stability under biotic (fungal disease), abiotic
      (wounding, salt, drought, heat and cold) stresses, in different plant tissues and
      in response to various plant growth regulators (methyl jasmonate, salicylic acid,
      abscisic acid). The data as analyzed by various software packages (geNorm,
      NormFinder, Bestkeeper and DeltaCt method) suggested that cyclophilin (CYP) is a
      most stable gene under wounding, heat, methyl jasmonate, different tissues and
      all stress conditions. T-SAND was found to be a best reference gene for salt and
      salicylic acid (SA) treated samples, while 26S ribosomal RNA (26S), ubiquitin
      (UBQ) and beta-tubulin (TUB) were the most stably expressed genes under drought,
      biotic and cold treatment respectively. For abscisic acid (ABA) treated samples
      18S-rRNA was found to stably expressed gene. Finally, the relative expression
      level of the three genes involved in the withanolide biosynthetic pathway was
      detected to validate the selection of reliable reference genes. The present work
      will significantly contribute to gene analysis studies in W. somnifera and
      facilitate in improving the quality of gene expression data in this plant as well
      as and other related plant species. 

PMID- 25769036
TI  - Saxitoxins and okadaic acid group: accumulation and distribution in invertebrate
      marine vectors from Southern Chile.
AB  - Harmful algae blooms (HABs) are the main source of marine toxins in the aquatic
      environment surrounding the austral fjords in Chile. Huichas Island (Aysen) has
      an history of HABs spanning more than 30 years, but there is limited
      investigation of the bioaccumulation of marine toxins in the bivalves and
      gastropods from the Region of Aysen. In this study, bivalves (Mytilus chilenses,
      Choromytilus chorus, Aulacomya ater, Gari solida, Tagelus dombeii and Venus
      antiqua) and carnivorous gastropods (Argobuccinum ranelliformes and Concholepas
      concholepas) were collected from 28 sites. Researchers analysed the accumulation
      of STX-group toxins using a LC with a derivatisation post column (LC-PCOX), while
      lipophilic toxins (OA-group, azapiracids, pectenotoxins and yessotoxins) were
      analysed using LC-MS/MS with electrospray ionisation (+/-) in visceral
      (hepatopancreas) and non-visceral tissues (mantle, adductor muscle, gills and
      foot). Levels of STX-group and OA-group toxins varied among individuals from the
      same site. Among all tissue samples, the highest concentrations of STX-group
      toxins were noted in the hepatopancreas in V. antiqua (95 +/- 0.1 MUg STX-eq 100
      g(-1)), T. dombeii (148 +/- 1.4 MUg STX-eq 100 g(-1)) and G. solida (3232 +/- 5.2
      MUg STX-eq 100 g(-1); p < 0.05); in the adductor muscle in M. chilensis (2495 +/-
      6.4 MUg STX-eq 100 g(-1); p < 0.05) and in the foot in C. concholepas (81 +/- 0.7
      MUg STX-eq 100 g(-1)) and T. dombeii (114 +/- 1.2 MUg STX-eq 100 g(-1)). The
      highest variability of toxins was detected in G. solida, where high levels of
      carbamate derivatives were identified (GTXs, neoSTX and STX). In addition to the
      detected hydrophilic toxins, OA-group toxins were detected (OA and DTX-1) with an
      average ratio of ~1:1. The highest levels of OA-group toxins were in the foot of
      C. concholepas, with levels of 400.3 +/- 3.6 MUg OA eq kg(-1) (p < 0.05) and with
      a toxic profile composed of 90% OA. A wide range of OA-group toxins was detected
      in M. chilensis with a toxicity < 80 MUg OA eq kg(-1), but with 74% of those
      toxins detected in the adductor muscle. In all evaluated species, there was no
      detection of lipophilic toxins associated with biotransformation in molluscs and
      carnivorous gastropods. In addition, the STX-group and OA-group toxin
      concentrations in shellfish was not associated with the presence of HAB. The
      ranking of toxin concentration in the tissues of most species was: digestive
      glands > mantle > adductor muscle for the STX-group toxins and foot > digestive
      gland for the OA-group toxins. These results gave a better understanding of the
      variability and compartmentalisation of STX-group and OA-group toxins in
      different bivalve and gastropod species from the south of Chile, and the analyses
      determined that tissues could play an important role in the biotransformation of
      STX-group toxins and the retention of OA-group toxins.

PMID- 25769033
TI  - Sera from children with autism induce autistic features which can be rescued with
      a CNTF small peptide mimetic in rats.
AB  - Autism is a neurodevelopmental disorder characterized clinically by impairments
      in social interaction and verbal and non-verbal communication skills as well as
      restricted interests and repetitive behavior. It has been hypothesized that
      altered brain environment including an imbalance in neurotrophic support during
      early development contributes to the pathophysiology of autism. Here we report
      that sera from children with autism which exhibited abnormal levels of various
      neurotrophic factors induced cell death and oxidative stress in mouse primary
      cultured cortical neurons. The effects of sera from autistic children were
      rescued by pre-treatment with a ciliary neurotrophic factor (CNTF) small peptide
      mimetic, Peptide 6 (P6), which was previously shown to exert its neuroprotective
      effect by modulating CNTF/JAK/STAT pathway and LIF signaling and by enhancing
      brain derived neurotrophic factor (BDNF) expression. Similar neurotoxic effects
      and neuroinflammation were observed in young Wistar rats injected
      intracerebroventricularly with autism sera within hours after birth. The autism
      sera injected rats demonstrated developmental delay and deficits in social
      communication, interaction, and novelty. Both the neurobiological changes and the
      behavioral autistic phenotype were ameliorated by P6 treatment. These findings
      implicate the involvement of neurotrophic imbalance during early brain
      development in the pathophysiology of autism and a proof of principle of P6 as a
      potential therapeutic strategy for autism. 

PMID- 25769037
TI  - Decreased peritoneal ovarian cancer growth in mice lacking expression of lipid
      phosphate phosphohydrolase 1.
AB  - Lysophosphatidic acid (LPA) is a bioactive lipid that enhances ovarian cancer
      cell proliferation, migration and invasion in vitro and stimulates peritoneal
      metastasis in vivo. LPA is generated through the action of autotaxin or
      phospholipases, and degradation begins with lipid phosphate phosphohydrolase
      (LPP)-dependent removal of the phosphate. While the effects of LPA on ovarian
      cancer progression are clear, the effects of LPA metabolism within the tumor
      microenvironment on peritoneal metastasis have not been reported. We examined the
      contribution of lipid phosphatase activity to ovarian cancer peritoneal
      metastasis using mice deficient in LPP1 expression. Homozygous deletion of LPP1
      (LPP1 KO) results in elevated levels and decreased turnover of LPA in vivo.
      Within 2 weeks of intraperitoneal injection of syngeneic mouse ovarian cancer
      cells, we observed enhanced tumor seeding in the LPP1 KO mice compared to wild
      type. However, tumor growth plateaued in the LPP1 KO mice by 3 weeks while tumors
      continued to grow in wild type mice. The decreased tumor burden was accompanied
      by increased apoptosis and no change in proliferation or angiogenesis. Tumor
      growth was restored and apoptosis reversed with exogenous administration of LPA.
      Together, these observations demonstrate that the elevated levels of LPA per se
      in LPP1 KO mice do not inhibit tumor growth. Rather, the data support the notion
      that either elevated LPA concentration or altered LPA metabolism affects other
      growth-promoting contributions of the tumor microenvironment. 

PMID- 25769038
TI  - "Double N": Evolution of the Surgical Technique for Laparoscopic Herniorrhaphy
      After 10-Year Experience in a Single Center.
AB  - INTRODUCTION: We describe our experience with the use of a modified technique for
      laparoscopic internal inguinal ring closure (peritoneal incision and double "N"
      stitch placement). We evaluate the technique in terms of feasibility, efficacy,
      and safety. MATERIALS AND METHODS: From November 2003 to March 2014 we performed
      1700 herniorraphies by laparoscopy. We selected 123 patients treated with the
      "double N" technique by the same surgical team, and we reviewed their notes
      analyzing demographic data, operative times, intra- and postoperative
      complications, and recurrence rate. The technique used is a modification of the
      Schier technique. Our technique consists of a partial lateral peritoneal 180
      degrees  incision around the internal inguinal ring and in the placement of a
      double stitch. The first stitch is used to approximate the muscles with the
      inguinal ligament, and the second one is used to close the peritoneum above them.
      RESULTS: The female to male ratio was 22:101. Mean age at surgery was 4.3 years
      (range, 1 month-12 years). Mean operative time was 30 minutes (range, 20-50
      minutes). There were 60 bilateral cases. There were no intraoperative
      complications. Two patients had reactive hydrocele treated conservatively, and 1
      patient developed umbilical infection. We did not identify any recurrence.
      CONCLUSIONS: Our early results suggest that the "double N" laparoscopic technique
      to close the internal inguinal ring in children is safe and efficient. We
      therefore suggest using this approach in children with a patent internal inguinal
      ring of >1 cm. The recurrence rate is low, but it should be better assessed by
      studies with longer follow-up.

PMID- 25769039
TI  - The production of nominal and verbal inflection in an agglutinative language:
      evidence from Hungarian.
AB  - The contrast between regular and irregular inflectional morphology has been
      useful in investigating the functional and neural architecture of language.
      However, most studies have examined the regular/irregular distinction in non
      agglutinative Indo-European languages (primarily English) with relatively simple
      morphology. Additionally, the majority of research has focused on verbal rather
      than nominal inflectional morphology. The present study attempts to address these
      gaps by introducing both plural and past tense production tasks in Hungarian, an
      agglutinative non-Indo-European language with complex morphology. Here we report
      results on these tasks from healthy Hungarian native-speaking adults, in whom we
      examine regular and irregular nominal and verbal inflection in a within-subjects
      design. Regular and irregular nouns and verbs were stem on frequency, word
      length, and phonological structure, and both accuracy and response times were
      acquired. The results revealed that the regular/irregular contrast yields similar
      patterns in Hungarian, for both nominal and verbal inflection, as in previous
      studies of non-agglutinative Indo-European languages: the production of irregular
      inflected forms was both less accurate and slower than of regular forms, both for
      plural and past-tense inflection. The results replicate and extend previous
      findings to an agglutinative language with complex morphology. Together with
      previous studies, the evidence suggests that the regular/irregular distinction
      yields a basic behavioral pattern that holds across language families and
      linguistic typologies. Finally, the study sets the stage for further research
      examining the neurocognitive substrates of regular and irregular morphology in an
      agglutinative non-Indo-European language. 

PMID- 25769041
TI  - The role of antibiotic prophylaxis in routine endoscopic retrograde
      cholangiopancreatography investigations as assessed prospectively in a nationwide
      study cohort.
AB  - OBJECTIVE: Risk factors for complications after endoscopic retrograde
      cholangiopancreatography (ERCP) with emphasis on the potential advantage of the
      use of prophylactic antibiotics were studied in a national population-based study
      cohort. MATERIALS AND METHODS: All ERCP procedures registered in the Swedish
      Registry of Gallstone Surgery and ERCP (GallRiks) between May 2005 and June 2013
      were analyzed. Patients with ongoing antibiotic treatment, incomplete
      registration or those who had not undergone an index ERCP were excluded. Risk
      factors for adverse events were analyzed. RESULTS: Data from 47,950 ERCPs were
      collected, but after applying the exclusion criteria, 31,188 examinations were
      analyzed. In the group receiving prophylactic antibiotics, the postoperative
      adverse event rate was 11.6% compared with 14.2% in the group without
      antibiotics. The odds ratio (OR) for the risk of postoperative adverse events in
      patients receiving prophylactic antibiotics was 0.74 (95% confidence interval
      [CI]: 0.69-0.79). When analyzing a subgroup of 21,893 ERCPs for the three most
      common indications (common bile duct stones, malignancy, and obstructive
      jaundice), the beneficial effect of prophylactic antibiotics on adverse events
      remained (OR = 0.76; 95% CI: 0.70-0.82). Further, in the subgroup of patients
      with obstructive jaundice, the administration of prophylactic antibiotics had a
      beneficial effect on septic complications (OR = 0.76; 95% CI: 0.58-0.97).
      CONCLUSION: The risk of adverse events after ERCP is reduced 26% if antibiotics
      are given prophylactically during ERCP investigations, as suggested by data
      gained from this national population-based study. However, in absolute terms, the
      reduction in adverse events by prophylactic antibiotics is modest (2.6%).

PMID- 25769040
TI  - Complete blood count reference intervals for healthy Han Chinese adults.
AB  - BACKGROUND: Complete blood count (CBC) reference intervals are important to
      diagnose diseases, screen blood donors, and assess overall health. However,
      current reference intervals established by older instruments and technologies and
      those from American and European populations are not suitable for Chinese samples
      due to ethnic, dietary, and lifestyle differences. The aim of this multicenter
      collaborative study was to establish CBC reference intervals for healthy Han
      Chinese adults. METHODS: A total of 4,642 healthy individuals (2,136 males and
      2,506 females) were recruited from six clinical centers in China (Shenyang,
      Beijing, Shanghai, Guangzhou, Chengdu, and Xi'an). Blood samples collected in
      K2EDTA anticoagulant tubes were analyzed. Analysis of variance was performed to
      determine differences in consensus intervals according to the use of data from
      the combined sample and selected samples. RESULTS: Median and mean platelet
      counts from the Chengdu center were significantly lower than those from other
      centers. Red blood cell count (RBC), hemoglobin (HGB), and hematocrit (HCT)
      values were higher in males than in females at all ages. Other CBC parameters
      showed no significant instrument-, region-, age-, or sex-dependent difference.
      Thalassemia carriers were found to affect the lower or upper limit of different
      RBC profiles. CONCLUSION: We were able to establish consensus intervals for CBC
      parameters in healthy Han Chinese adults. RBC, HGB, and HCT intervals were
      established for each sex. The reference interval for platelets for the Chengdu
      center should be established independently.

PMID- 25769042
TI  - Workplace interventions to reduce HIV and TB stigma among health care workers -
      Where do we go from here?
AB  - Fear of stigma and discrimination among health care workers (HCWs) in South
      African hospitals is thought to be a major factor in the high rates of HIV and
      tuberculosis infection experienced in the health care workforce. The aim of the
      current study is to inform the development of a stigma reduction intervention in
      the context of a large multicomponent trial. We analysed relevant results of four
      feasibility studies conducted in the lead up to the trial. Our findings suggest
      that a stigma reduction campaign must address community and structural level
      drivers of stigma, in addition to individual level concerns, through a
      participatory and iterative approach. Importantly, stigma reduction must not only
      be embedded in the institutional management of HCWs but also be attentive to the
      localised needs of HCWs themselves. 

PMID- 25769043
TI  - Osteogenic differentiation of human mesenchymal stem cells in mineralized
      alginate matrices.
AB  - Mineralized biomaterials are promising for use in bone tissue engineering.
      Culturing osteogenic cells in such materials will potentially generate biological
      bone grafts that may even further augment bone healing. Here, we studied
      osteogenic differentiation of human mesenchymal stem cells (MSC) in an alginate
      hydrogel system where the cells were co-immobilized with alkaline phosphatase
      (ALP) for gradual mineralization of the microenvironment. MSC were embedded in
      unmodified alginate beads and alginate beads mineralized with ALP to generate a
      polymer/hydroxyapatite scaffold mimicking the composition of bone. The initial
      scaffold mineralization induced further mineralization of the beads with
      nanosized particles, and scanning electron micrographs demonstrated presence of
      collagen in the mineralized and unmineralized alginate beads cultured in
      osteogenic medium. Cells in both types of beads sustained high viability and
      metabolic activity for the duration of the study (21 days) as evaluated by
      live/dead staining and alamar blue assay. MSC in beads induced to differentiate
      in osteogenic direction expressed higher mRNA levels of osteoblast-specific genes
      (RUNX2, COL1AI, SP7, BGLAP) than MSC in traditional cell cultures. Furthermore,
      cells differentiated in beads expressed both sclerostin (SOST) and dental matrix
      protein-1 (DMP1), markers for late osteoblasts/osteocytes. In conclusion, Both
      ALP-modified and unmodified alginate beads provide an environment that enhance
      osteogenic differentiation compared with traditional 2D culture. Also, the ALP
      modified alginate beads showed profound mineralization and thus have the
      potential to serve as a bone substitute in tissue engineering. 

PMID- 25769045
TI  - Clostridial co-infection episodes in commercial laying hens.
AB  - The present report describes two outbreaks of serious enteritis in commercial
      laying hens where Clostridium perfringens and Clostridium colinum were
      simultaneously detected. At the age of 44 and 31 weeks, two laying hen flocks
      showed an increase of the mortality rate and a worsening of productive
      performance. Post-mortem examination revealed intestinal necrotic-haemorrhagic
      ulcerations and hepatic focal necrosis. The bacteriological examination yielded
      the isolation of C. colinum and C. perfringens toxin type A, NetB positive. In
      one outbreak, C. colinum was detected also by polymerase chain reaction in all
      the intestines of affected birds. In laying hens, C. colinum has never been
      isolated but only suspected as the causative agent of a slight enteric disease
      called duodenal focal necrosis. The present case report was characterized by
      severe enteritis presumably due to the synergistic effect of C. colinum and C.
      perfringens. 

PMID- 25769044
TI  - RSV vaccine-enhanced disease is orchestrated by the combined actions of distinct
      CD4 T cell subsets.
AB  - There is no currently licensed vaccine for respiratory syncytial virus (RSV)
      despite being the leading cause of lower respiratory tract infections in
      children. Children previously immunized with a formalin-inactivated RSV (FI-RSV)
      vaccine exhibited enhanced respiratory disease following natural RSV infection.
      Subsequent studies in animal models have implicated roles for CD4 T cells,
      eosinophils and non-neutralizing antibodies in mediating enhanced respiratory
      disease. However, the underlying immunological mechanisms responsible for the
      enhanced respiratory disease and other disease manifestations associated with FI
      RSV vaccine-enhanced disease remain unclear. We demonstrate for the first time
      that while CD4 T cells mediate all aspects of vaccine-enhanced disease, distinct
      CD4 T cell subsets orchestrate discrete and specific disease parameters. A Th2
      biased immune response, but not eosinophils specifically, was required for airway
      hyperreactivity and mucus hypersecretion. In contrast, the Th1-associated
      cytokine TNF-alpha was necessary to mediate airway obstruction and weight loss.
      Our data demonstrate that individual disease manifestations associated with FI
      RSV vaccine-enhanced disease are mediated by distinct subsets of CD4 T cells. 

PMID- 25769046
TI  - Direct blood dry LAMP: a rapid, stable, and easy diagnostic tool for Human
      African Trypanosomiasis.
AB  - Loop-mediated isothermal amplification (LAMP) is a rapid and sensitive tool used
      for the diagnosis of a variety of infectious diseases. One of the advantages of
      this method over the polymerase chain reaction is that DNA amplification occurs
      at a constant temperature, usually between 60-65 degrees C; therefore, expensive
      devices are unnecessary for this step. However, LAMP still requires complicated
      sample preparation steps and a well-equipped laboratory to produce reliable and
      reproducible results, which limits its use in resource-poor laboratories in most
      developing countries. In this study, we made several substantial modifications to
      the technique to carry out on-site diagnosis of Human African Trypanosomiasis
      (HAT) in remote areas using LAMP. The first essential improvement was that LAMP
      reagents were dried and stabilized in a single tube by incorporating trehalose as
      a cryoprotectant to prolong shelf life at ambient temperature. The second
      technical improvement was achieved by simplifying the sample preparation step so
      that DNA or RNA could be amplified directly from detergent-lysed blood samples.
      With these modifications, diagnosis of HAT in local clinics or villages in
      endemic areas becomes a reality, which could greatly impact on the application of
      diagnosis not only for HAT but also for other tropical diseases. 

PMID- 25769047
TI  - Thoracoscopic plication of the diaphragm in infants in the first 3 months of
      life.
AB  - PURPOSE: Thoracoscopic plication of the diaphragm is an alternative to
      conventional surgical treatment of diaphragmatic evisceration via thoracotomy in
      neonates and infants. The aim of this study is to compare results of treatment by
      these two methods in the past 11 years. MATERIALS AND METHODS: We studied the
      data of 35 neonates who underwent standard posterolateral thoracotomy (18
      patients; Group I) or video-assisted thoracoscopic surgery (17 patients; Group
      II) for diaphragmatic plication. The two groups were compared for patient
      demographics, operative reports, and postoperative parameters. RESULTS: The
      groups were similar in terms of demographics and preoperative parameters. There
      was a significant difference in mean operative time between the open and
      thoracoscopic procedure (71.67 minutes versus 51.76 minutes; P<.05). Duration of
      care in the neonatal intensive unit and length of hospital stay were
      significantly shorter in Group II (5.89 days versus 3.23 days [P<.05] and 13.06
      days versus 9.88 days [P<.05]). Early postoperative complications (hemothorax,
      pneumothorax) were frequent in the thoracotomy group (Group I) (16.67% versus 0%;
      P>.05). Recurrence of diaphragmatic evisceration was observed only in the
      thoracotomy group (11.11% versus 0%; P=.486). CONCLUSIONS: Thoracoscopic
      plication of the diaphragm in infants in the first 3 months of life demonstrates
      better results than open surgery.

PMID- 25769048
TI  - Confidence analysis of standard deviational ellipse and its extension into higher
      dimensional euclidean space.
AB  - Standard deviational ellipse (SDE) has long served as a versatile GIS tool for
      delineating the geographic distribution of concerned features. This paper firstly
      summarizes two existing models of calculating SDE, and then proposes a novel
      approach to constructing the same SDE based on spectral decomposition of the
      sample covariance, by which the SDE concept is naturally generalized into higher
      dimensional Euclidean space, named standard deviational hyper-ellipsoid (SDHE).
      Then, rigorous recursion formulas are derived for calculating the confidence
      levels of scaled SDHE with arbitrary magnification ratios in any dimensional
      space. Besides, an inexact-newton method based iterative algorithm is also
      proposed for solving the corresponding magnification ratio of a scaled SDHE when
      the confidence probability and space dimensionality are pre-specified. These
      results provide an efficient manner to supersede the traditional table lookup of
      tabulated chi-square distribution. Finally, synthetic data is employed to
      generate the 1-3 multiple SDEs and SDHEs. And exploratory analysis by means of
      SDEs and SDHEs are also conducted for measuring the spread concentrations of Hong
      Kong's H1N1 in 2009. 

PMID- 25769049
TI  - Proactive and reactive transmission power control for energy-efficient on-body
      communications.
AB  - In wireless body sensor network (WBSNs), the human body has an important effect
      on the performance of the communication due to the temporal variations caused and
      the attenuation and fluctuation of the path loss. This fact suggests that the
      transmission power must adapt to the current state of the link in a way that it
      ensures a balance between energy consumption and packet loss. In this paper, we
      validate our two transmission power level policies (reactive and predictive
      approaches) using the Castalia simulator. The integration of our experimental
      measurements in the simulator allows us to easily evaluate complex scenarios,
      avoiding the difficulties associated with a practical realization. Our results
      show that both schemes perform satisfactorily, providing overall energy savings
      of 24% and 22% for a case of study, as compared to the maximum transmission power
      mode. 

PMID- 25769050
TI  - A new gaze estimation method considering external light.
AB  - Gaze tracking systems usually utilize near-infrared (NIR) lights and NIR cameras,
      and the performance of such systems is mainly affected by external light sources
      that include NIR components. This is ascribed to the production of additional
      (imposter) corneal specular reflection (SR) caused by the external light, which
      makes it difficult to discriminate between the correct SR as caused by the NIR
      illuminator of the gaze tracking system and the imposter SR. To overcome this
      problem, a new method is proposed for determining the correct SR in the presence
      of external light based on the relationship between the corneal SR and the pupil
      movable area with the relative position of the pupil and the corneal SR. The
      experimental results showed that the proposed method makes the gaze tracking
      system robust to the existence of external light. 

PMID- 25769051
TI  - Comparison of the detection characteristics of trace species using laser-induced
      breakdown spectroscopy and laser breakdown time-of-flight mass spectrometry.
AB  - The rapid and precise element measurement of trace species, such as mercury,
      iodine, strontium, cesium, etc. is imperative for various applications,
      especially for industrial needs. The elements mercury and iodine were measured by
      two detection methods for comparison of the corresponding detection features. A
      laser beam was focused to induce plasma. Emission and ion signals were detected
      using laser-induced breakdown spectroscopy (LIBS) and laser breakdown time-of
      flight mass spectrometry (LB-TOFMS). Multi-photon ionization and electron impact
      ionization in the plasma generation process can be controlled by the pressure and
      pulse width. The effect of electron impact ionization on continuum emission,
      coexisting molecular and atomic emissions became weakened in low pressure
      condition. When the pressure was less than 1 Pa, the plasma was induced by laser
      dissociation and multi-photon ionization in LB-TOFMS. According to the
      experimental results, the detection limits of mercury and iodine in N2 were 3.5
      ppb and 60 ppb using low pressure LIBS. The mercury and iodine detection limits
      using LB-TOFMS were 1.2 ppb and 9.0 ppb, which were enhanced due to different
      detection features. The detection systems of LIBS and LB-TOFMS can be selected
      depending on the condition of each application. 

PMID- 25769052
TI  - Indocyanine green angiographic evidence of choroiditis in scleroderma.
AB  - PURPOSE: The purpose of this case report was to demonstrate evidence of
      indocyanine green angiography leakage consistent with choroiditis in a patient
      with scleroderma. METHODS: In this case report, the patient underwent a variety
      of tests and examinations, including systemic evaluation, full ocular
      examination, skin biopsy, indocyanine green, and fluorescein angiography testing.
      A 52-year-old man had blurred vision centrally in both eyes. Vision was 20/25 and
      20/20. Posterior examination showed cotton-wool spots in both eyes. The patient
      met European League against Rheumatism (EULAR) criteria for scleroderma. RESULTS:
      Fluorescein angiography confirmed the presence of leakage from the retinal
      vessels. More importantly, indocyanine green angiography revealed choroidal
      vessel leakage in both eyes. This provided evidence of choroiditis before vessel
      obliteration. Previous studies have shown evidence of choriocapillaris
      obliteration. Choroidal vessel leakage, however, has not been reported in
      patients with scleroderma. CONCLUSION: The results of this case demonstrate the
      usefulness of indocyanine green angiography in detecting the presence of
      choroiditis in scleroderma.

PMID- 25769054
TI  - Does prevention pay?

PMID- 25769053
TI  - Transcriptome sequence analysis of an ornamental plant, Ananas comosus var.
      bracteatus, revealed the potential unigenes involved in terpenoid and
      phenylpropanoid biosynthesis.
AB  - BACKGROUND: Ananas comosus var. bracteatus (Red Pineapple) is an important
      ornamental plant for its colorful leaves and decorative red fruits. Because of
      its complex genome, it is difficult to understand the molecular mechanisms
      involved in the growth and development. Thus high-throughput transcriptome
      sequencing of Ananas comosus var. bracteatus is necessary to generate large
      quantities of transcript sequences for the purpose of gene discovery and
      functional genomic studies. RESULTS: The Ananas comosus var. bracteatus
      transcriptome was sequenced by the Illumina paired-end sequencing technology. We
      obtained a total of 23.5 million high quality sequencing reads, 1,555,808 contigs
      and 41,052 unigenes. In total 41,052 unigenes of Ananas comosus var. bracteatus,
      23,275 unigenes were annotated in the NCBI non-redundant protein database and
      23,134 unigenes were annotated in the Swiss-Port database. Out of these, 17,748
      and 8,505 unigenes were assigned to gene ontology categories and clusters of
      orthologous groups, respectively. Functional annotation against Kyoto
      Encyclopedia of Genes and Genomes Pathway database identified 5,825 unigenes
      which were mapped to 117 pathways. The assembly predicted many unigenes that were
      previously unknown. The annotated unigenes were compared against pineapple, rice,
      maize, Arabidopsis, and sorghum. Unigenes that did not match any of those five
      sequence datasets are considered to be Ananas comosus var. bracteatus unique. We
      predicted unigenes encoding enzymes involved in terpenoid and phenylpropanoid
      biosynthesis. CONCLUSION: The sequence data provide the most comprehensive
      transcriptomic resource currently available for Ananas comosus var. bracteatus.
      To our knowledge; this is the first report on the de novo transcriptome
      sequencing of the Ananas comosus var. bracteatus. Unigenes obtained in this
      study, may help improve future gene expression, genetic and genomics studies in
      Ananas comosus var. bracteatus.

PMID- 25769055
TI  - Antipsychotic prescribing: do conflict of interest policies make a difference?
AB  - BACKGROUND: Academic medical centers (AMCs) have increasingly adopted conflict of
      interest policies governing physician-industry relationships; it is unclear how
      policies impact prescribing. OBJECTIVES: To determine whether 9 American
      Association of Medical Colleges (AAMC)-recommended policies influence
      psychiatrists' antipsychotic prescribing and compare prescribing between academic
      and nonacademic psychiatrists. RESEARCH DESIGN: We measured number of
      prescriptions for 10 heavily promoted and 9 newly introduced/reformulated
      antipsychotics between 2008 and 2011 among 2464 academic psychiatrists at 101
      AMCs and 11,201 nonacademic psychiatrists. We measured AMC compliance with 9 AAMC
      recommendations. Difference-in-difference analyses compared changes in
      antipsychotic prescribing between 2008 and 2011 among psychiatrists in AMCs
      compliant with >= 7/9 recommendations, those whose institutions had lesser
      compliance, and nonacademic psychiatrists. RESULTS: Ten centers were AAMC
      compliant in 2008, 30 attained compliance by 2011, and 61 were never compliant.
      Share of prescriptions for heavily promoted antipsychotics was stable and
      comparable between academic and nonacademic psychiatrists (63.0%-65.8% in 2008
      and 62.7%-64.4% in 2011). Psychiatrists in AAMC-compliant centers were slightly
      less likely to prescribe these antipsychotics compared with those in never
      compliant centers (relative odds ratio, 0.95; 95% CI, 0.94-0.97; P < 0.0001).
      Share of prescriptions for new/reformulated antipsychotics grew from 5.3% in 2008
      to 11.1% in 2011. Psychiatrists in AAMC-compliant centers actually increased
      prescribing of new/reformulated antipsychotics relative to those in never
      compliant centers (relative odds ratio, 1.39; 95% CI, 1.35-1.44; P < 0.0001), a
      relative increase of 1.1% in probability. CONCLUSIONS: Psychiatrists exposed to
      strict conflict of interest policies prescribed heavily promoted antipsychotics
      at rates similar to academic psychiatrists and nonacademic psychiatrists exposed
      to less strict or no policies.

PMID- 25769056
TI  - Systematic review of risk adjustment models of hospital length of stay (LOS).
AB  - BACKGROUND: Policy decisions in health care, such as hospital performance
      evaluation and performance-based budgeting, require an accurate prediction of
      hospital length of stay (LOS). This paper provides a systematic review of risk
      adjustment models for hospital LOS, and focuses primarily on studies that use
      administrative data. METHODS: MEDLINE, EMBASE, Cochrane, PubMed, and EconLit were
      searched for studies that tested the performance of risk adjustment models in
      predicting hospital LOS. We included studies that tested models developed for the
      general inpatient population, and excluded those that analyzed risk factors only
      correlated with LOS, impact analyses, or those that used disease-specific scales
      and indexes to predict LOS. RESULTS: Our search yielded 3973 abstracts, of which
      37 were included. These studies used various disease groupers and
      severity/morbidity indexes to predict LOS. Few models were developed specifically
      for explaining hospital LOS; most focused primarily on explaining resource
      spending and the costs associated with hospital LOS, and applied these models to
      hospital LOS. We found a large variation in predictive power across different LOS
      predictive models. The best model performance for most studies fell in the range
      of 0.30-0.60, approximately. CONCLUSIONS: The current risk adjustment
      methodologies for predicting LOS are still limited in terms of models,
      predictors, and predictive power. One possible approach to improving the
      performance of LOS risk adjustment models is to include more disease-specific
      variables, such as disease-specific or condition-specific measures, and
      functional measures. For this approach, however, more comprehensive and
      standardized data are urgently needed. In addition, statistical methods and
      evaluation tools more appropriate to LOS should be tested and adopted.

PMID- 25769057
TI  - A new Elixhauser-based comorbidity summary measure to predict in-hospital
      mortality.
AB  - BACKGROUND: Recently, van Walraven developed a weighted summary score (VW) based
      on the 30 comorbidities from the Elixhauser comorbidity system. One of the 30
      comorbidities, cardiac arrhythmia, is currently excluded as a comorbidity
      indicator in administrative datasets such as the Nationwide Inpatient Sample
      (NIS), prompting us to examine the validity of the VW score and its use in the
      NIS. METHODS: Using data from the 2009 Maryland State Inpatient Database, we
      derived weighted summary scores to predict in-hospital mortality based on the
      full (30) and reduced (29) set of comorbidities and compared model performance of
      these and other comorbidity summaries in 2009 NIS data. RESULTS: Weights of our
      derived scores were not sensitive to the exclusion of cardiac arrhythmia. When
      applied to NIS data, models containing derived summary scores performed nearly
      identically (c statistics for 30 and 29 variable-derived summary scores: 0.804
      and 0.802, respectively) to the model using all 29 comorbidity indicators
      (c=0.809), and slightly better than the VW score (c=0.793). Each of these models
      performed substantially better than those based on a simple count of Elixhauser
      comorbidities (c=0.745) or a categorized count (0, 1, 2, or >= 3 comorbidities;
      c=0.737). CONCLUSIONS: The VW score and our derived scores are valid in the NIS
      and are statistically superior to summaries using simple comorbidity counts.
      Researchers wishing to summarize the Elixhauser comorbidities with a single value
      should use the VW score or those derived in this study.

PMID- 25769059
TI  - Myopathic characteristics in septic mechanically ventilated patients.
AB  - PURPOSE OF REVIEW: Survivors of a critical illness may experience poor physical
      function and quality of life as a result of reduced skeletal muscle mass and
      strength during their acute illness. Patients diagnosed with sepsis are
      particularly at risk, and mechanical ventilation may result in diaphragm
      dysfunction. Interest in the interaction of these conditions is both growing and
      important to understand for individualized patient care. RECENT FINDINGS: This
      review describes developments in the presentation of both diaphragm and limb
      myopathy in critical illness, as measured from muscle biopsy and at the bedside
      with various imaging and strength-testing modalities. The influence of unloading
      of the diaphragm with mechanical ventilation and peripheral muscles with
      immobilization in septic patients has been recently questioned. Systemic
      inflammation appears to primarily accelerate and accentuate dysfunction, which
      may be remedied by early mobilization and augmented with developing muscle and/or
      nerve stimulation techniques. SUMMARY: Many acute muscle changes in septic
      patients are likely to stem from pre-existing impairments, which should provide
      context for clinical evaluations of strength. During illness, sarcolemmal injury
      promotes a cascade of intra-cellular abnormalities. As unique characteristics of
      ICU-acquired weakness and differential effects on muscle groups are understood,
      early diagnosis and management should be facilitated.

PMID- 25769058
TI  - A hybrid approach to identify subsequent breast cancer using pathology and
      automated health information data.
AB  - PURPOSE: Many cancer registries do not capture recurrence; thus, outcome studies
      have often relied on time-intensive and costly manual chart reviews. Our goal was
      to build an effective and efficient method to reduce the numbers of chart reviews
      when identifying subsequent breast cancer (BC) using pathology and electronic
      health records. We evaluated our methods in an independent sample. METHODS: We
      developed methods for identifying subsequent BC (recurrence or second primary)
      using a cohort of 17,245 women diagnosed with early-stage BC from 2 health plans.
      We used a combination of information from pathology report reviews and an
      automated data algorithm to identify subsequent BC (for those lesions without
      pathologic confirmation). Test characteristics were determined for a
      developmental (N=175) and test (N=500) set. RESULTS: Sensitivity and specificity
      of our hybrid approach were robust [96.7% (87.6%-99.4%) and 92.1% (85.1%-96.1%),
      respectively] in the developmental set. In the test set, the sensitivity,
      specificity, and negative predictive value were also high [96.9% (88.4%-99.5%),
      92.4% (89.4%-94.6%), and 99.5% (98.0%-99.0%), respectively]. The positive
      predictive value was lower (65.6%, 55.2%-74.8%). Chart review was required for
      10.9% of the 17,245 women; 2946 (17.0%) women developed subsequent BC over a 14
      year period. The date of subsequent BC identified by the algorithm was concordant
      with full chart reviews. CONCLUSIONS: We developed an efficient and effective
      hybrid approach that decreased the number of charts needed to be manually
      reviewed by approximately 90%, to determine subsequent BC occurrence and disease
      free survival time.

PMID- 25769060
TI  - Is TP53INP2 a critical regulator of muscle mass?
AB  - PURPOSE OF REVIEW: The main aim of this review is to summarize current knowledge
      of tumor protein p53-inducible nuclear protein 2 (TP53INP2) function and its role
      in skeletal muscle proteostasis. RECENT FINDINGS: Autophagy is directly involved
      in the regulation of skeletal muscle mass. Thus, excessive autophagy is
      associated with several diseases that cause muscle wasting, and it promotes the
      loss of muscle protein. Furthermore, compromised autophagy also leads to muscle
      atrophy. In this regard, TP53INP2 activates autophagy in skeletal muscle, thus
      causing a reduction in muscle mass. Moreover, TP53INP2 gain of function enhances
      muscle wasting in a highly catabolic context such as in streptozotocin-induced
      diabetes. However, TP53INP2 is naturally repressed in human insulin resistance
      and in murine models of diabetes. These observations suggest that TP53INP2
      repression would reduce muscle atrophy under conditions that favor protein loss
      in skeletal muscle. SUMMARY: To date, there is no effective treatment for muscle
      wasting. Thus, the identification of new putative pharmacological targets to
      effectively treat this devastating condition is crucial. Given current knowledge
      about the role of TP53INP2 in skeletal muscle, this protein may be an optimal
      candidate to target for the prevention of muscle wasting.

PMID- 25769061
TI  - Muscle wasting in cancer: the role of mitochondria.
AB  - PURPOSE OF REVIEW: The aim of the present review is to examine the impact of
      mitochondrial dysfunction in cancer cachexia. RECENT FINDINGS: Oxidative pathways
      are altered in this tissue during muscle wasting and this seems to be a
      consequence of mitochondrial abnormalities that include altered morphology and
      function, decreased ATP synthesis and uncoupling. SUMMARY: An alteration of
      energy balance is the immediate cause of cachexia. Both alterations in energy
      intake and expenditure are responsible for the wasting syndrome associated with
      different types of pathological conditions, such as cancer. Different types of
      molecular mechanisms contribute to energy expenditure and, therefore, involuntary
      body weight loss, one of which is mitochondrial dysfunction.

PMID- 25769062
TI  - Human milk pasteurization: benefits and risks.
AB  - PURPOSE OF REVIEW: Recent findings substantiate that the optimal method of
      nourishing preterm, very low birth weight infants (VLBW, born <1500 g) is through
      appropriately nutrient-enriched human milk, which is frequently provided as
      pasteurized donor milk. The availability of donor milk for VLBW infants during
      initial hospitalization continues to increase with the launch of new milk banks
      in North America. The majority of North American neonatal ICUs now have written
      policies governing the provision of donor milk. The purpose of this review is to
      summarize recent evidence regarding the risks and benefits of pasteurization of
      human milk and outcomes associated with its provision to VLBW preterm infants.
      RECENT FINDINGS: Studies investigating the impact of collection, storage and
      pasteurization on the bacteriostatic, immunologic and nutritional aspects of
      human milk continue to be published, generally revealing a partial, but not
      complete reduction in bioactivity. Risk of contamination of pasteurized donor
      human milk with pathogenic agents is mitigated through pasteurization. New
      pasteurization methods aiming to maintain the safety of pooled human milk while
      better preserving bioactivity are under investigation. SUMMARY: Provision of a
      human milk-derived diet to preterm VLBW infants is associated with improved
      outcomes.

PMID- 25769063
TI  - Probiotic interventions in infantile colic.
AB  - PURPOSE OF REVIEW: Up until 2014, the use of probiotics in infantile colic has
      shown promise. However, the past year has seen the publication of controversial
      results and rigorous debate on whether probiotics are effective in infantile
      colic. It is time to review the evidence and discuss whether probiotics should be
      used for infants with colic. RECENT FINDINGS: Despite previous trials indicating
      the probiotic Lactobacillus reuteri DSM 17938 to be effective in treating
      infantile colic in predominantly breastfed infants, a recent larger trial
      controversially concluded it to be ineffective for both breastfed and formula-fed
      infants. A further smaller trial indicated it to be effective, yet again, for
      treating breastfed infants with colic. Meanwhile, L. reuteri DSM 17938 has been
      suggested, for the first time, to be possibly effective in preventing infantile
      colic. SUMMARY: L. reuteri DSM 17938 may be effective for certain subgroups of
      breastfed infants with colic, and this will be clarified by an ongoing individual
      participant data meta-analysis. At this stage, the probiotic cannot be
      recommended for treating infantile colic in formula-fed infants, nor can it be
      routinely used to prevent infantile colic.

PMID- 25769064
TI  - Absence of Activation-induced Cytidine Deaminase, a Regulator of Class Switch
      Recombination and Hypermutation in B Cells, Suppresses Aorta Allograft
      Vasculopathy in Mice.
AB  - BACKGROUND: Antibody-mediated rejection is caused in part by increasing
      circulation/production of donor-specific antibody (DSA). Activation-induced
      cytidine deaminase (AID) is a key regulator of class switch recombination and
      somatic hypermutation of immunoglobulin in B cells, yet its role in antibody
      mediated transplant rejection remains unclear. We show here that AID deficiency
      in mice enables suppression of allograft vasculopathy (AV) after aorta
      transplantation, a DSA-mediated process. METHODS: Splenocytes from C57BL/6 J (B6)
      AID(-/-) mice were used for determining in vitro proliferation responses,
      alloreactivity, cell surface marker expression, and antibody production. BALB/c
      mouse aortas were transplanted into B6 AID(-/-) mice with or without FK506
      treatment. Blood and aorta grafts were harvested on day 30 after transplantation
      and were subjected to DSA, histological, and immunohistological analyses.
      RESULTS: The AID(-/-) splenocytes were comparable to wild type splenocytes in
      proliferation responses, alloreactivity, and expression of cell surface markers
      in vitro. However, they completely failed to produce immunoglobulin G, although
      they were not impaired in immunoglobulin M production relative to controls.
      Furthermore, BALB/c aorta grafts from B6 AID(-/-) recipient mice on day 30 after
      transplantation showed reduced signs of AV compared to the grafts from B6 wild
      type recipient mice which had severe vascular intimal hyperplasia, interstitial
      fibrosis, and inflammation. Treatment with FK506 produced a synergistic effect in
      the grafts from AID(-/-) recipients with further reduction of intimal hyperplasia
      and fibrosis scores. CONCLUSIONS: The AID deficiency inhibits DSA-mediated AV
      after aorta transplantation in mice. We propose that AID could be a novel
      molecular target for controlling antibody-mediated rejection in organ
      transplantation.

PMID- 25769065
TI  - Association of Kidney Graft Loss With De Novo Produced Donor-Specific and Non
      Donor-Specific HLA Antibodies Detected by Single Antigen Testing.
AB  - BACKGROUND: The association of donor-specific HLA antibodies (DSA) with kidney
      graft failure has been addressed previously; however, the majority of studies
      were based on small numbers of patients with graft failure. METHODS: We
      investigated 83 patients with failed kidney transplants for a possible
      association of de novo development and persistence or loss of pre-existing DSA
      with graft failure. Single Antigen Bead assay-detected DSA and non-DSA antibodies
      were compared between patients with graft loss and matched controls with
      functioning grafts. RESULTS: The incidence of weak de novo DSA or non-DSA at a
      mean fluorescence intensity of 500 or higher was higher in the graft loss than in
      the nonrejector group (76% vs 40%, P < 0.001). Because of the low number of
      patients developing de novo DSA, the DSA results did not reach statistical
      significance (only 22% of patients with graft loss developed de novo DSA).
      However, at all cutoffs, there was a significantly higher rate of graft loss in
      patients with de novo non-DSA. The incidence of strong pretransplant DSA that
      persist after transplantation was higher in the graft loss group (10% vs 1%, P =
      0.034). When C1q-binding ability in sera of rejectors and nonrejectors with
      posttransplant de novo or persistent DSA was compared, none of the nonrejectors
      demonstrated C1q positivity, whereas 43% of patients with graft loss showed C1q
      positive antibodies, although not necessarily donor-specific (P < 0.001).
      CONCLUSIONS: Our data show that the posttransplant presence of persisting or de
      novo HLA antibodies, especially if C1q binding, is associated with graft loss,
      even if the antibodies are not specific for mismatched donor HLA.

PMID- 25769066
TI  - Prognostic value of cardiac tests in potential kidney transplant recipients: a
      systematic review.
AB  - BACKGROUND: Whether abnormal myocardial perfusion scintigraphy (MPS), dobutamine
      stress echocardiography (DSE) or coronary angiography, performed during
      preoperative evaluation for potential kidney transplant recipients, predicts
      future cardiovascular morbidity is unclear. We assessed test performance for
      predicting all-cause mortality, cardiovascular mortality and major adverse
      cardiac events (MACE). METHODS: We searched MEDLINE and EMBASE (to February
      2014), appraised studies, and calculated risk differences and relative risk
      ratios (RRR) with 95% confidence intervals (95% CI) using random effects meta
      analysis. RESULTS: Fifty-two studies (7401 participants) contributed data to the
      meta-analysis. Among the different tests, similar numbers of patients experienced
      MACE after an abnormal test result compared with a normal result (risk
      difference: MPS 20 per 100 patients tested [95% CI, 0.11-0.29], DSE 24 [95% CI,
      0.10-0.38], and coronary angiography 20 [95% CI, 0.08-0.32; P = 0.91]). Although
      there was some evidence that coronary angiography was better at predicting all
      cause mortality than MPS (RRR, 0.69; 95% CI, 0.49-0.96; P = 0.03) and DSE (RRR,
      0.72; 95% CI, 0.50-1.02; P = 0.06), noninvasive tests were as good as coronary
      angiography at predicting cardiovascular mortality (RRR, MPS, 0.89; 95% CI, 0.38
      2.10; P = 0.78; DSE, 1.09; 95% CI, 0.12-10.05; P = 0.93), and MACE (RRR: MPS,
      1.09; 95% CI, 0.64-1.86; P = 0.74; DSE, 1.56; 95% CI, 0.71-3.45; P = 0.25).
      CONCLUSIONS: Noninvasive tests are as good as coronary angiography at predicting
      future adverse cardiovascular events in advanced chronic kidney disease. However,
      a substantial number of people with negative test results go on to experience
      adverse cardiac events.

PMID- 25769067
TI  - Is there an optimal strategy for pretransplant cardiovascular screening?

PMID- 25769068
TI  - Data sharing.

PMID- 25769069
TI  - What is "data sharing" and why should biomedical researchers embrace it?

PMID- 25769070
TI  - Immunoprotection and Functional Improvement of Allogeneic Islets in Diabetic
      Mice, Using a Stable Indoleamine 2,3-Dioxygenase Producing Scaffold.
AB  - BACKGROUND: We have previously shown that an immunomodulatory enzyme, indoleamine
      2,3-dioxygenase (IDO) in dermal fibroblasts generates a tryptophan-deficient
      environment that selectively inhibits proliferation and induces apoptosis of
      bystander CD4+ and CD8+ T cells, but not pancreatic islets. Because these immune
      cells are involved in islet allograft rejection, we hypothesized that
      transplantation of islets embedded in a novel 3-dimensional composite scaffold
      within which stable IDO-expressing fibroblasts serve as source of local
      immunosuppression would lead to normoglycemia in a streptozotocin-induced
      diabetic mouse model. METHODS: Islet grafts were prepared by embedding stable IDO
      expressing fibroblasts and allogeneic islets into a protease-resistant composite
      scaffold. Islets function and survival were evaluated in vitro using
      immunohistochemistry. Allografts were transplanted under the kidney capsule of
      streptozotocin-induced diabetic mice; viability, function, and criteria for graft
      take were evaluated. Flow cytometry was performed to determine specific
      intragraft, draining lymph nodes and spleen T-cell population, and splenocytes
      alloantigen responsiveness of graft recipients. RESULTS: The results of a series
      of in vitro experiments revealed that IDO-expressing fibroblasts do not
      compromise islet function or survival. The expression of IDO suppressed the
      proliferation of alloantigen-stimulated splenocytes. The in vivo experiments
      revealed that local IDO expression delivered by lentiviral vector prolonged islet
      allograft survival (51.0 +/- 2.9 days) by increasing the population of FOXP3+
      regulatory T cells at the graft site and graft-draining lymph nodes and
      preventing T-cell infiltration. CONCLUSIONS: This study shows that incorporation
      of islets within our novel matrix that is equipped with stable IDO-expressing
      fibroblasts prolongs allograft survival.

PMID- 25769071
TI  - Prospective Monitoring of Donor-specific Anti-HLA Antibodies After
      Intestine/Multivisceral Transplantation: Significance of De Novo Antibodies.
AB  - BACKGROUND: Presence of circulating donor-specific antibodies (DSA) may be
      associated with worse clinical outcomes after intestine/multivisceral
      transplantation. METHODS: In 79 intestine/multivisceral recipients, sera were
      prospectively screened for DSA by Luminex Single antigen test at 1, 3, 6, 9, 12,
      18, 24, and 36 months after transplantation. Standard immunosuppression included
      thymoglobulin-rituximab induction and tacrolimus-prednisone maintenance. C4d
      staining was performed retrospectively on biopsies in patients that developed
      acute rejection (AR). RESULTS: Twenty-two (28%) patients developed de novo DSA at
      a median posttransplant period of 3 (1-36) months. De novo DSA were observed in
      10 of 40 liver-including and 12 of 39 liver-excluding transplants (P = 0.57).
      Occurrence of AR was slightly higher in patients with de novo DSA (45% vs 33%,
      respectively; P = 0.41). Similarly, chronic rejection (14% vs 5%; P = 0.21) and
      graft loss due to AR (18% vs 7%; P = 0.14) were numerically higher in patients
      with de novo DSA. Only 35% patients experiencing AR had circulating de novo DSA
      at the time of AR. Antibody-mediated rejection was diagnosed in 6 patients based
      on C4d staining, of these 2 patients had circulating de novo DSA at the time of
      biopsy. CONCLUSIONS: De novo DSA formation, particularly early in the
      posttransplant course may be associated with trends toward worse outcomes.
      However, its significance in the pathophysiology of AR remains uncertain. Studies
      focusing mechanisms of DSA-related graft injury and intragraft DSA detection
      might provide further insight into this issue.

PMID- 25769072
TI  - Dealing With Public Solicitation of Organs From Living Donors--An ELPAT View.
AB  - Although transplant professionals have initially been reluctant to perform
      transplants after public solicitation of organs from living donors, nowadays
      these transplants are increasingly being performed and reported. After clarifying
      the existing terminology, we elaborate an operational definition of public
      solicitation that is consistent with the Ethical, Legal, and Psychosocial Aspects
      of Transplantation classification for living organ donation. Our aim is to
      critically assess this phenomenon, from a legal, moral, and practical
      perspective, and to offer some recommendations. From a legal point of view, we
      analyze the current situation in the Europe and the United States. From a moral
      perspective, we evaluate the various arguments used in the literature, both in
      favor and against. Finally, we offer a set of recommendations aimed at maximizing
      the organ donor pool while safeguarding the interests of potential living donors.

PMID- 25769073
TI  - Evaluation of Alemtuzumab Versus Basiliximab Induction: A Retrospective Cohort
      Study in Lung Transplant Recipients.
AB  - BACKGROUND: Acute cellular rejection (ACR) is a major early complication after
      lung transplantation (LT) and is a risk factor for chronic rejection. Induction
      immunosuppression has been used as a strategy to reduce early ACR. Recently, our
      LT program changed our primary induction protocol from basiliximab with standard
      maintenance immunosuppression to alemtuzumab induction with reduced dose
      maintenance immunosuppression. The objective of this study was to compare
      incidence of ACR after this change in the first 6 months after transplantation.
      METHODS: A retrospective, cohort review of patients 18 years or older, which
      received their first LT between January 2010 and September 2012. RESULTS: The
      primary outcome was comparison of average lung biopsy scores at 6 months.
      Secondary outcomes included development of grade A2 or higher rejection,
      infectious outcomes, overall graft and patient survival. At 6 months, the average
      biopsy score was significantly lower in the alemtuzumab group than the
      basiliximab group (0.12 +/- 0.29 vs 0.74 +/- 0.67; P < 0.0001) (Table 2). Grade 2
      or higher rejection was significantly higher in the basiliximab group (P <
      0.0001). CONCLUSIONS: Alemtuzumab provided superior outcomes in regard to average
      biopsy score and lower incidence of grade 2 or higher rejection at 6 months.
      There were no differences in infectious complications or overall graft or patient
      survival between the 2 groups.

PMID- 25769074
TI  - Lymph Node Stromal Fiber ER-TR7 Modulates CD4+ T Cell Lymph Node Trafficking and
      Transplant Tolerance.
AB  - BACKGROUND: Trafficking and differentiation of naive CD4+ and regulatory T cells
      (Treg) within the lymph node (LN) are integral for tolerance induction. The LN is
      comprised of stromal fibers that dictate lymphocyte migration and LN structure,
      organization, and microanatomic domains. Distribution of the stromal fiber ER-TR7
      changes within the LN after antigenic challenge, but the contributions of ER-TR7
      to the resulting immune response remain undefined. We hypothesized that these
      stromal fiber structural changes affect T cell fate and subsequently allograft
      survival. METHODS: C57BL/6 mice were left naive (untreated) or made immune or
      tolerant (donor-specific BALB/c splenocyte transfusion -/+ anti-CD40L monoclonal
      antibody), or made tolerant and received anti-ER-TR7 monoclonal antibody. Donor
      specific T-cell migration was visualized by adoptive transfer of
      carboxyfluorescein diacetate, succinimidyl ester-labeled TEa T cell receptor
      transgenic CD4+ cells. Immunohistochemistry was performed on LNs to detect
      stromal fiber distribution, structure, CCL21 presence, and Treg and donor
      specific cell location relative to high endothelial venules (HEV). Naive,
      tolerant, and tolerant + anti-ER-TR7 mice received BALB/c heterotopic cardiac
      allografts and graft survival was monitored. RESULTS: The ER-TR7 distribution
      changed after the induction of tolerance vs. immunity. Treating tolerant mice
      with anti-ER-TR7 altered HEV basement membrane structure and the distribution of
      CCL21 within the LN. These differences were mirrored by changes in the migration
      of naive and Treg cells within and surrounding the HEV. Anti-ER-TR7 prevented
      tolerance induction and resulted in allograft inflammation and rejection.
      CONCLUSIONS: These results identify ER-TR7 as an important component of LN
      structure in tolerance and a direct target for immune modulation.

PMID- 25769075
TI  - T cells Exhibit Reduced Signal Transducer and Activator of Transcription 5
      Phosphorylation and Upregulated Coinhibitory Molecule Expression After Kidney
      Transplantation.
AB  - BACKGROUND: T-cell depletion therapy is associated with diminished interleukin
      (IL)-7/IL-15-dependent homeostatic proliferation resulting in incomplete T-cell
      repopulation. Furthermore, it is associated with impaired T-cell functions. We
      hypothesized that this is the result of impaired cytokine responsiveness of T
      cells, through affected signal transducer and activator of transcription (STAT)5
      phosphorylation and upregulation of coinhibitory molecules. MATERIALS AND
      METHODS: Patients were treated with T cell-depleting rabbit antithymocyte
      globulin (rATG) (6 mg/kg, n = 17) or nondepleting, anti-CD25 antibody
      (basiliximab, 2 * 40 mg, n = 25) induction therapy, in combination with
      tacrolimus, mycophenolate mofetil, and steroids. Before and the first year after
      transplantation, IL-7 and IL-2 induced STAT5 phosphorylation, and the expression
      of the coinhibitory molecules programmed cell death protein 1 (PD-1), T cell
      immunoglobulin mucin-3 (TIM-3), lymphocyte activation gene-3 (LAG-3), cytotoxic T
      lymphocyte-associated protein 4 (CTLA-4), cluster of differentiation (CD) 160,
      and CD244 was measured by flow cytometry. RESULTS: The first year after rATG,
      CD4+, and CD8+ T cells were affected in their IL-7-dependent phosphorylation of
      STAT5 (pSTAT5) which was most outspoken in the CD8+ memory population. The
      capacity of CD4+ and CD8+ T cells to pSTAT5 in response to IL-2 decreased after
      both rATG and basiliximab therapy. After kidney transplantation, the percentage
      of TIM-3+, PD-1+, and CD160+CD4+ T cells and the percentage of CD160+ and
      CD244+CD8+ T cells increased, with no differences in expression between rATG- and
      basiliximab-treated patients. The decrease in pSTAT5 capacity CD8+ T cells and
      the increase in coinhibitory molecules were correlated. CONCLUSIONS: We show that
      memory T cells in kidney transplant patients, in particular after rATG treatment,
      have decreased cytokine responsiveness by impaired phosphorylation of STAT5 and
      have increased expression of coinhibitory molecules, processes which were
      correlated in CD8+ T cells.

PMID- 25769077
TI  - Clinical Utility of Urinary Cytology to Detect BK Viral Nephropathy.
AB  - BACKGROUND: Reactivation of BK polyoma virus can result in destructive viral
      allograft nephropathy (BKVAN) with limited treatment options. Screening programs
      using surrogate markers of viral replication are important preventive strategies,
      guiding immunosuppression reduction. METHODS: We prospectively evaluated the
      diagnostic test performance of urinary decoy cells and urinary SV40T
      immunochemistry of exfoliated cells, to screen for BKVAN, (defined by reference
      histology with SV40 immunohistochemistry, n = 704 samples), compared with
      quantitative viremia, from 211 kidney and 141 kidney-pancreas transplant
      recipients. RESULTS: The disease prevalence of BKVAN was 2.6%. Decoy cells
      occurred in 95 of 704 (13.5%) samples, with a sensitivity of 66.7%, specificity
      of 88.6%, positive predictive value (PPV) of 11.7%, and negative predictive value
      of 98.5% to predict histologically proven BKVAN. Quantification of decoy cells
      improved the PPV to 32.1% (10 >= cells threshold). Immunohistochemical staining
      of urinary exfoliated cells for SV40T improved sensitivity to 85.7%, detecting
      atypical or degenerate infected cells (specificity of 92.3% and PPV of 33.3%),
      but was hampered by technical failures. Viremia occurred in 90 of 704 (12.8%)
      with sensitivity of 96.3%, specificity of 90.3%, PPV of 31.5%, and negative
      predictive value of 99.8%. The receiver-operator curve performance of
      quantitative viremia surpassed decoy cells (area under the curve of 0.95 and
      0.79, respectively, P = 0.0018 for differences). Combining decoy cell and BK
      viremia in a diagnostic matrix improved prediction of BKVAN and diagnostic risk
      stratification, especially for high-level positive results. CONCLUSIONS: Although
      quantified decoy cells are acceptable surrogate markers of BK viral replication
      with unexceptional test performances, quantitative viremia displayed superior
      test characteristics and is suggested as the screening test of choice.

PMID- 25769076
TI  - Conditioning With Sevoflurane in Liver Transplantation: Results of a Multicenter
      Randomized Controlled Trial.
AB  - BACKGROUND: During times of organ scarcity and extended use of liver grafts,
      protective strategies in transplantation are gaining importance. We demonstrated
      in the past that volatile anesthetics such as sevoflurane attenuate ischemia
      reperfusion injury during liver resection. In this randomized study, we examined
      if volatile anesthetics have an effect on acute graft injury and clinical
      outcomes after liver transplantation. METHODS: Cadaveric liver transplant
      recipients were enrolled from January 2009 to September 2012 at 3 University
      Centers (Zurich/Sao Paulo/Ghent). Recipients were randomly assigned to propofol
      (control group) or sevoflurane anesthesia. Postoperative peak of aspartate
      transaminase was defined as primary endpoint, secondary endpoints were early
      allograft dysfunction, in-hospital complications, intensive care unit, and
      hospital stay. RESULTS: Ninety-eight recipients were randomized to propofol (n =
      48) or sevoflurane (n = 50). Median peak aspartate transaminase after
      transplantation was 925 (interquartile range, 512-3274) in the propofol and 1097
      (interquartile range, 540-2633) in the sevoflurane group. In the propofol arm, 11
      patients (23%) experienced early allograft dysfunction, 7 (14%) in the
      sevoflurane one (odds ratio, 0.64 (0.20 to 2.02, P = 0.45). There were 4
      mortalities (8.3%) in the propofol and 2 (4.0%) in the sevoflurane group. Overall
      and major complication rates were not different. An effect on clinical outcomes
      was observed favoring the sevoflurane group (less severe complications), but
      without significance. CONCLUSIONS: This first multicenter trial comparing
      propofol with sevoflurane anesthesia in liver transplantation shows no difference
      in biochemical markers of acute organ injury and clinical outcomes between the 2
      regimens. Sevoflurane has no significant added beneficial effect on ischemia
      reperfusion injury compared to propofol.

PMID- 25769078
TI  - Evaluation of MicroRNA375 as a Novel Biomarker for Graft Damage in Clinical Islet
      Transplantation.
AB  - BACKGROUND: Early and sensitive detection of islet graft damage is essential for
      improving posttransplant outcomes. MicroRNA 375 (miR375) has been reported as a
      biomarker of pancreatic beta-cell death in small animal models. METHODS: The
      miR375 levels were measured in purified human islets, sera from patients with
      autologous and allogeneic islet transplantation as well as total pancreatectomy
      alone (nontransplanted group). The miR375 levels were also determined in a
      miniaturized in vitro tube model comprising human islets and autologous blood.
      RESULTS: The miR375 expression level in islets was dose-dependent (P < 0.001) and
      significantly elevated after islet damage in plasma in the in vitro model (P =
      0.003). Clinical analysis revealed that circulating miR375 levels in both
      autologous and allogeneic islet recipients were significantly elevated for 7 days
      after islet infusion, compared with the nontransplanted group (P = 0.005 and
      <0.001, respectively). Furthermore, miR375 detected the difference in islet graft
      damage among 3 different anti-inflammatory protocols for clinical autologous
      transplantation (P < 0.01). CONCLUSIONS: Circulating miR375 can be a reliable
      biomarker to detect graft damage in clinical islet transplantation because serum
      C-peptide and proinsulin levels are difficult to interpret due to the influence
      of multiple factors, such as beta-cell stress and physiological response.

PMID- 25769079
TI  - Contribution of Revised International Prognostic Scoring System Cytogenetics to
      Predict Outcome After Allogeneic Stem Cell Transplantation for Myelodysplastic
      Syndromes: A Study From the French Society of Bone Marrow Transplantation and
      Cellular Therapy.
AB  - BACKGROUND: The prognosis of myelodysplastic syndromes (MDS) after allogeneic
      stem cell transplantation is critically determined by cytogenetic abnormalities,
      as previously defined by International Prognostic Scoring System (IPSS)
      cytogenetics. It has been shown that a new cytogenetic classification, included
      in the IPSS-R (cytogenetic-IPSS-R [C-IPSS-R]), can better predict the outcome of
      untreated MDS patients. METHODS: In this study, we assessed the impact of the
      IPSS-R cytogenetic score (C-IPSS-R) on the outcome of 367 MDS patients
      transplanted from HLA-identical siblings or HLA allele-matched unrelated donors.
      RESULTS: According to the C-IPSS-R, 178 patients (48%) fell in the good risk, 102
      (28%) in the intermediate risk, 77 (21%) in the poor risk, and 10 (3%) in the
      very poor risk group. In multivariate analysis, after a median follow-up of 4
      years, the poor and very poor-risk categories correlated with shorter overall
      survival (OS) (4-year OS, 32%; hazard ratio [HR], 1.59; P = 0.009 and OS, 10%;
      HR, 3.18; P = 0.002, respectively) and higher cumulative incidence of relapse
      (CIR) (CIR, 52%; HR, 1.82; P = 0.004 and CIR, 60%; HR, 2.44; P = 0.060,
      respectively). CONCLUSIONS: Overall, the C-IPSS-R changed the IPSS cytogenetic
      risk only in 8% of cases but identified a new risk group, the very poor C-IPSS-R
      category, with dismal outcome after allogeneic stem cell transplantation (10% 4
      year OS, 60% 4-year CIR). Posttransplantation maintenance therapy should be
      investigated in prospective trials for patients with high-risk C-IPSS-R
      karyotypes.

PMID- 25769080
TI  - The effects of fluorine-contained molecules on improving the polymer solar cell
      by curing the anomalous S-shaped I-V curve.
AB  - In this study, we investigate the effects of fluorinated poly(3,4-ethylene
      dioxythiophene):poly(styrenesulfonate) buffer layer on the performance of polymer
      photovoltaic cells. We demonstrate for the first time, the deterioration of the
      device performance can be effectively mended by modifying the interface between
      the active layer and buffer layer with heptadecafluoro-1,1,2,2-tetra-hydro-decyl
      trimethoxysilane (PFDS) and perfluorononane. Device performance shows a
      substantial enhancement of short-circuit current from 7.90 to 9.39 mA/cm(2) and
      fill factor from 27% to 53%. The overall device efficiency was improved from
      0.98% to 3.12% for PFDS modified device. The mechanism of S-shape curing is also
      discussed. In addition, the stability of modified devices shows significant
      improvement than those without modification. The efficiency of the modified
      devices retains about half (1.88%) of its initial efficiency (4.1%) after 30 d
      compared to the unmodified ones (0.61%), under air atmosphere. 

PMID- 25769082
TI  - Use of intercostal perforating veins and long arterial grafts for latissimus
      myocutaneous free flap reconstruction of radiated low back wounds.

PMID- 25769081
TI  - RECG maintains plastid and mitochondrial genome stability by suppressing
      extensive recombination between short dispersed repeats.
AB  - Maintenance of plastid and mitochondrial genome stability is crucial for
      photosynthesis and respiration, respectively. Recently, we have reported that
      RECA1 maintains mitochondrial genome stability by suppressing gross
      rearrangements induced by aberrant recombination between short dispersed repeats
      in the moss Physcomitrella patens. In this study, we studied a newly identified
      P. patens homolog of bacterial RecG helicase, RECG, some of which is localized in
      both plastid and mitochondrial nucleoids. RECG partially complements recG
      deficiency in Escherichia coli cells. A knockout (KO) mutation of RECG caused
      characteristic phenotypes including growth delay and developmental and
      mitochondrial defects, which are similar to those of the RECA1 KO mutant. The
      RECG KO cells showed heterogeneity in these phenotypes. Analyses of RECG KO
      plants showed that mitochondrial genome was destabilized due to a recombination
      between 8-79 bp repeats and the pattern of the recombination partly differed from
      that observed in the RECA1 KO mutants. The mitochondrial DNA (mtDNA) instability
      was greater in severe phenotypic RECG KO cells than that in mild phenotypic ones.
      This result suggests that mitochondrial genomic instability is responsible for
      the defective phenotypes of RECG KO plants. Some of the induced recombination
      caused efficient genomic rearrangements in RECG KO mitochondria. Such loci were
      sometimes associated with a decrease in the levels of normal mtDNA and
      significant decrease in the number of transcripts derived from the loci. In
      addition, the RECG KO mutation caused remarkable plastid abnormalities and
      induced recombination between short repeats (12-63 bp) in the plastid DNA. These
      results suggest that RECG plays a role in the maintenance of both plastid and
      mitochondrial genome stability by suppressing aberrant recombination between
      dispersed short repeats; this role is crucial for plastid and mitochondrial
      functions. 

PMID- 25769083
TI  - Torsional stability of the femur after harvest of the medial femoral condyle
      corticocancellous flap.
AB  - BACKGROUND: Increasingly large segments of medial femoral condyle (MFC)
      corticocancellous flaps have been harvested for transfer. Biomechanical
      evaluations demonstrated no osseous stability impairment under axial loading
      regardless of flap size harvested. The purpose of this study was to determine the
      donor site's response to torsional forces. METHODS: Dual-energy X-ray
      absorptiometry (DEXA) scanning was performed on 16 pairs of cadaver legs followed
      by removal of all soft tissues, except knee capsule and ligaments. Specimens were
      randomly assigned to three groups with bone harvest defects measuring 3, 5, or 7
      cm in length and a control group with no osseous resection. Torsional load was
      applied until fracture or ligamentous failure. RESULTS: Bone failure rates were
      12.5, 12.5, 28.6, and 55.6% for control, 3, 5, and 7 cm groups, respectively.
      Bone failure rate increased with increasing harvest size; the 7 cm group
      demonstrated a significantly higher rate compared with the other groups combined
      (55.6 vs. 17.4%; p = 0.03). Failure torque was 45.5, 29.35, 27.4, and 30.83 Nm
      for the control, 3, 5, and 7 cm groups, respectively (p = 0.11). Harvest of any
      size segment resulted in a significant decrease in failure torque (p = 0.01).
      Bone mineral density (BMD) and Z-scores were no different among groups (p = 0.79
      and 0.59, respectively). A direct relationship was identified between force
      required for failure and BMD (p = 0.02) and Z-scores (p = 0.05) but not for
      failure location and BMD (p = 0.09) or Z-scores (p = 0.94). CONCLUSION: MFC
      corticocancellous flap harvest of any size decreases donor site failure torque.
      Flap harvests > 7 cm demonstrate a higher frequency of iatrogenic fracture and
      therefore warrant caution with torsional loading of the knee postoperatively.
      Routine preoperative DEXA scans may not be warranted.

PMID- 25769084
TI  - Highest Impact Articles in Microsurgery: A Citation Analysis.
AB  - BACKGROUND: Microsurgery has developed significantly since the inception of the
      first surgical microscope. There have been few attempts to describe "classic"
      microsurgery articles. In this study citation analysis was done to identify the
      most highly cited clinical and basic science articles published in five peer
      reviewed plastic surgery journals. METHODS: Thomson/Reuters web of knowledge was
      used to identify the most highly cited microsurgery articles from five journals:
      Plastic and Reconstructive Surgery, Annals of Plastic Surgery, Journal of
      Plastic, Reconstructive & Aesthetic Surgery, Journal of Reconstructive
      Microsurgery, and Microsurgery. Articles were identified and sorted based on the
      number of citations and citations per year. RESULTS: The 50 most cited clinical
      and basic science articles were identified. For clinical articles, number of
      total citations ranged from 120 to 691 (mean, 212.38) and citations per year
      ranged from 30.92 to 3.05 (mean, 9.33). The most common defect site was the head
      and neck (n = 15, 30%), and flaps were perforator and muscle/musculocutaneous
      flaps (n = 10 each, 20%, respectively). For basic science articles, number of
      citations ranged from 71 to 332 (mean, 130.82) and citations per year ranged from
      2.20 to 11.07 (mean, 5.27). There were 27 animal, 21 cadaveric, and 2 combined
      studies. CONCLUSIONS: The most highly cited microsurgery articles are a direct
      reflection of the educational and clinical trends. Awareness of the most
      frequently cited articles may serve as a basis for core knowledge in the
      education of plastic surgery trainees. LEVEL OF EVIDENCE: III.

PMID- 25769085
TI  - Perioperative management for microsurgical free tissue transfer: survey of
      current practices with a comparison to the literature.
AB  - BACKGROUND: Free tissue transfer is an important technique in reconstructive
      surgery. Due to a lack of evidence-based guidelines, a variety of practices are
      currently implemented by microsurgeons. This motivated the authors to define
      current practices and identify key areas where these practices can be optimized.
      METHODS: An anonymous online survey consisting of 40 questions regarding
      perioperative management for free tissue transfer was generated via an online
      survey platform. Questions covered topics including patient selection,
      anesthesia, patient temperature, fluid management, vasoactive agents, and
      analgesia. Approval was received from the American Society for Reconstructive
      Microsurgery and the survey was distributed to its members via two emails, in May
      and June 2013. RESULTS: Survey responses were received from 82/706 microsurgeons
      (12% response rate): 36% of respondents believed that complications of these
      cases are "sometimes" or "often" related to anesthesia; 55% of respondents stated
      they do not use specific goals and protocols to guide fluid management for these
      cases; 38% of respondents stated that they have no target range for hemoglobin
      and hematocrit for these procedures; and 70% of respondents stated that they do
      not permit the use of a vasopressor in nonemergent situations. CONCLUSION:
      Current practices remain exceedingly diverse and at times differ from best
      practices, which may be identified from the available literature. Key areas where
      patient care can be standardized and optimized include anesthesia, patient
      temperature, fluid management, the use of vasoactive agents, and analgesic
      medications. Standardized, evidence-based guidelines have the potential to
      further improve patient care and free flap outcomes.

PMID- 25769086
TI  - Impact of Specialty Training on the Association between Flap Size and Incidence
      of Complications following Microvascular Head and Neck Reconstruction for Cancer.
AB  - BACKGROUND: The scope of otolaryngology and plastic surgery overlap within head
      and neck reconstruction is increasing; yet comparative outcome studies between
      these two subspecialties are limited. METHODS: A retrospective review was
      performed on all patients who underwent microvascular reconstruction of a
      postablative head and neck defect at a quaternary academic medical center between
      January 2000 and October 2011. Postoperative outcomes were reviewed by
      subspecialty and Mann-Whitney analysis was used to investigate any flap size
      differences between cohorts with and without complications. RESULTS: A
      consecutive series of 129 (66.8%) otolaryngology cases and 64 (33.2%) plastic
      surgery cases comprised the entire study sample. Plastic surgery flaps were
      significantly larger than otolaryngology flaps (9.7 vs. 8.5 cm, p = 0.004). Flap
      complication rates (31.8 vs. 37.5%, p = 0.429) and flap failure rates (5.4 vs.
      4.7%, p = 0.429) were comparable between subspecialties. However, a significant
      difference in flap size was evident between the cohorts with and without flap
      complications following microvascular reconstruction by otolaryngology (9.18 vs.
      8.15 cm, p = 0.042). This difference was not detected following reconstruction by
      plastic surgery (9.34 vs. 9.04 cm, p = 0.225). For the overall sample, there was
      a correlation between increasing flap size and higher tumor stages (significant
      at T4, p = 0.003) as well as advanced T-stage and medical complications (p =
      0.004). CONCLUSION: Plastic surgeons should maintain an active role in the
      reconstruction of complex, microvascular head and neck cases such as those that
      require larger flaps and/or of advanced T-stages.

PMID- 25769087
TI  - Freestyle multiple propeller flap reconstruction (jigsaw puzzle approach) for
      complicated back defects.
AB  - BACKGROUND: The reconstruction of the posterior trunk remains to be a challenge
      as defects can be extensive, with deep dead space, and fixation devices exposed.
      Our goal was to achieve a tension-free closure for complex defects on the
      posterior trunk. PATIENTS AND METHODS: From August 2006 to May 2013, 18 cases
      were reconstructed with multiple flaps combining perforator(s) and local skin
      flaps. The reconstructions were performed using freestyle approach. Starting with
      propeller flap(s) in single or multilobed design and sequentially in conjunction
      with adjacent random pattern flaps such as fitting puzzle. All defects achieved
      tensionless primary closure. The final appearance resembled a jigsaw puzzle-like
      appearance. RESULTS: The average size of defect was 139.6 cm(2) (range, 36-345
      cm(2)). A total of 26 perforator flaps were used in addition to 19 random pattern
      flaps for 18 cases. In all cases, a single perforator was used for each propeller
      flap. The defect and the donor site all achieved tension-free closure. The
      reconstruction was 100% successful without flap loss. One case of late infection
      was noted at 12 months after surgery. CONCLUSION: Using multiple lobe designed
      propeller flaps in conjunction with random pattern flaps in a freestyle approach,
      resembling putting a jigsaw puzzle together, we can achieve a tension-free
      closure by distributing the tension to multiple flaps, supplying sufficient
      volume to obliterate dead space, and have reliable vascularity as the flaps do
      not need to be oversized. This can be a viable approach to reconstruct extensive
      defects on the posterior trunk.

PMID- 25769088
TI  - Safety of the supraclavicular artery island flap in the setting of neck
      dissection and radiation therapy.
AB  - BACKGROUND: The supraclavicular artery island flap (SAIF) has recently been
      repopularized as a versatile and reliable option for reconstruction of
      oncological head and neck defects. Prior ipsilateral neck dissection or
      irradiation is considered a relative contraindication to its use. The aim of this
      study was to describe the safety and utility of the SAIF for head and neck
      reconstruction in the setting of neck dissection and radiation. METHODS: A
      retrospective chart review was performed of consecutive SAIF reconstructions at
      two institutions between May 2011 and 2014. In addition to demographic data,
      comorbidities, indications, surgical characteristics, data about radiation
      treatment, and neck dissection were specifically recorded. Donor and recipient
      site complications were noted. Fisher exact test was performed to analyze if neck
      dissection or radiation were associated with complications. RESULTS: A total of
      22 patients underwent SAIF reconstruction for an array of head and neck defects.
      Donor site infection was noted in one patient. Recipient site complications
      included, wound dehiscence (n = 2), orocutaneous fistula (n = 1), carotid blowout
      (n = 1), and total flap loss (n = 1). There was no association between prior neck
      dissection or radiation treatment and flap loss (p = 1.00). CONCLUSION: The SAIF
      is safe for use in patients who have had an ipsilateral neck dissection involving
      level IV or V lymph nodes and/or radiation treatment to the neck. It can be used
      alone or in combination with other flaps for closure of a variety of head and
      neck defects.

PMID- 25769089
TI  - Facial nerve reconstruction and facial disfigurement after radical parotidectomy.
AB  - BACKGROUND: The importance of facial contouring with facial nerve reconstruction
      following total and radical parotidectomy is often overlooked. The goal of this
      study was to quantify the level of facial disfigurement and nerve dysfunction
      following reconstruction of the facial nerve, with or without reconstruction of
      the contours, using free tissue transfer. METHODS: A total of 26 patients with
      radical parotidectomy and facial nerve reconstruction were included in this
      retrospective study. Of the 26 patients, 15 underwent follow-up interviews and
      evaluation of facial nerve function and disfigurement using three different
      scales: the regional House-Brackmann (H-B) scale, the Facial Clinimetric
      Evaluation (FaCE) Scale, and the observer-rated disfigurement scale. RESULTS: Of
      the 15 evaluated patients, 8 patients underwent free tissue transfer. Mean follow
      up time was 39 months (median, 35; range, 11-65 months). Of the 15 patients, 10
      patients had good or moderate function according to the H-B mouth scale (median
      score, 4; range, 2-5), and satisfactory eye closure was observed in 10 patients
      (median score, 3; range, 2-5). The mean disfigurement value rated by the
      physician was 5 (scale, 1-9), with a mean patient rating of 4. Subjective total
      FaCE score varied significantly (mean, 52; range, 13-93). CONCLUSIONS: Facial
      nerve and soft tissue reconstruction are highly beneficial to patients undergoing
      radical parotidectomy.

PMID- 25769090
TI  - Effects of oxidized and reduced forms of methylthioninium in two transgenic mouse
      tauopathy models.
AB  - Given the repeated failure of amyloid-based approaches in Alzheimer's disease,
      there is increasing interest in tau-based therapeutics. Although methylthioninium
      (MT) treatment was found to be beneficial in tau transgenic models, the brain
      concentrations required to inhibit tau aggregation in vivo are unknown. The
      comparative efficacy of methylthioninium chloride (MTC) and leucomethylthioninium
      salts (LMTX; 5-75 mg/kg; oral administration for 3-8 weeks) was assessed in two
      novel transgenic tau mouse lines. Behavioural (spatial water maze, RotaRod motor
      performance) and histopathological (tau load per brain region) proxies were
      applied. Both MTC and LMTX dose-dependently rescued the learning impairment and
      restored behavioural flexibility in a spatial problem-solving water maze task in
      Line 1 (minimum effective dose: 35 mg MT/kg for MTC, 9 mg MT/kg for LMTX) and
      corrected motor learning in Line 66 (effective doses: 4 mg MT/kg).
      Simultaneously, both drugs reduced the number of tau-reactive neurons,
      particularly in the hippocampus and entorhinal cortex in Line 1 and in a more
      widespread manner in Line 66. MT levels in the brain followed a sigmoidal
      concentration-response relationship over a 10-fold range (0.13-1.38 MUmol/l).
      These data establish that diaminophenothiazine compounds, like MT, can reverse
      both spatial and motor learning deficits and reduce the underlying tau pathology,
      and therefore offer the potential for treatment of tauopathies. 

PMID- 25769091
TI  - Improvement of ketamine-induced social withdrawal in rats: the role of 5-HT7
      receptors.
AB  - Social withdrawal, one of the core negative symptoms of schizophrenia, can be
      modelled in the social interaction (SI) test in rats using N-methyl-D-aspartate
      receptor glutamate receptor antagonists. We have recently shown that amisulpride,
      an antipsychotic with a high affinity for serotonin 5-HT7 receptors, reversed
      ketamine-induced SI deficits in rats. The aim of the present study was to further
      elucidate the potential involvement of 5-HT7 receptors in the prosocial action of
      amisulpride. Acute administration of amisulpride (3 mg/kg) and SB-269970 (1
      mg/kg), a 5-HT7 receptor antagonist, reversed ketamine-induced social withdrawal,
      whereas sulpiride (20 or 30 mg/kg) and haloperidol (0.2 mg/kg) were ineffective.
      The 5-HT7 receptor agonist AS19 (10 mg/kg) abolished the prosocial efficacy of
      amisulpride (3 mg/kg). The coadministration of an inactive dose of SB-269970 (0.2
      mg/kg) showed the prosocial effects of inactive doses of amisulpride (1 mg/kg)
      and sulpiride (20 mg/kg). The anxiolytic chlordiazepoxide (2.5 mg/kg) and the
      antidepressant fluoxetine (2.5 mg/kg) were ineffective in reversing ketamine
      induced SI deficits. The present study suggests that the antagonism of 5-HT7
      receptors may contribute towards the mechanisms underlying the prosocial action
      of amisulpride. These results may have therapeutic implications for the treatment
      of negative symptoms in schizophrenia and other disorders characterized by social
      withdrawal.

PMID- 25769093
TI  - Statistics commentary series: commentary #8-effect sizes.

PMID- 25769092
TI  - Cocaine self-administration punished by intravenous histamine in adolescent and
      adult rats.
AB  - Adolescence is a transitional phase marked by a heightened vulnerability to
      substances of abuse. It has been hypothesized that both increased sensitivity to
      reward and decreased sensitivity to aversive events may drive drug-use liability
      during this phase. To investigate possible age-related differences in sensitivity
      to the aversive consequences of drug use, adolescent and adult rats were compared
      on self-administration of cocaine before, during, and after a 10-day period in
      which an aversive agent, histamine, was added to the cocaine solution. Adult and
      adolescent female rats were trained to self-administer intravenous cocaine (0.4
      mg/kg/infusion) over 10 sessions (2 h/session; 2 sessions/day). Histamine (4
      mg/kg/infusion) was then added directly into the cocaine solution for the next 10
      sessions. Finally, the cocaine/histamine solution was replaced with a cocaine
      only solution, and rats continued to self-administer cocaine (0.4 mg/kg) for 20
      sessions. Compared with adolescent rats, adult rats showed a greater decrease in
      cocaine self-administration when it was punished with intravenous histamine
      compared with their baseline cocaine self-administration rates. These results
      suggest that differences in the sensitivity to negative consequences of drug use
      may partially explain developmental differences in drug use vulnerability. 

PMID- 25769094
TI  - Statistics Commentary Series: Commentary #9-Sample Size Made Easy (Power a Bit
      Less So).

PMID- 25769095
TI  - Ignorance isn't bliss: why patients become angry.
AB  - Patients with cognitive limitations may struggle understanding complex arguments
      and feel overwhelmed by the need to choose among medical options that they poorly
      understand. Such struggle may result in frustration and anger directed at the
      physician. The aim of the present study is to explain the characteristics
      underlying such situations. A decision tree is modeled to capture the choice that
      every patient has to make after receiving medical advice. Patient choices are
      phrased in terms of a threshold probability for accepting or rejecting advice by
      physicians. To a patient with poor understanding of medical exigencies all
      differences between present or absent disease state, prognosis, and risks of
      intervention may seem largely arbitrary and meaningless. With little or no
      guidance to make an informed decision, taking any medical action is deemed wasted
      and harmful, whereas inaction leaves the underlying medical problem unsolved.
      Both choices appear equally ineffective with respect to the patient's symptoms
      and therefore unappealing. As shown by applying threshold analysis to a patient
      in a state of ignorance, no threshold probability for following medical advice
      exists. Patients with cognitive limitations will become frustrated and angry by a
      seemingly dismal situation without good alternatives to choose from. 

PMID- 25769096
TI  - Associations between lipodystrophy or antiretroviral medications and cirrhosis in
      patients with HIV infection or HIV/HCV coinfection.
AB  - BACKGROUND: Many HIV antiretroviral medications have been associated with chronic
      liver injury. HIV-infected patients frequently develop HIV and highly active
      antiretroviral treatment-associated lipodystrophy syndrome (HALS), characterized
      by accumulation of intra-abdominal fat, insulin resistance, and hepatic
      steatosis. We sought to determine whether long-term exposure to specific
      antiretroviral medications or the presence of HALS predispose HIV-infected
      patients to the development of cirrhosis. METHODS: HIV-infected patients with
      cirrhosis who received care in the Veterans Affairs Healthcare System nationally
      in 2009 were matched by hepatitis C virus (HCV) coinfection status and year of
      first visit for HIV to the Veterans Affairs Healthcare System with HIV-infected
      patients without cirrhosis in a 1 : 3 ratio. RESULTS: Among HIV/HCV coinfected
      patients (593 with cirrhosis and 1591 matched controls), HALS was associated with
      a significantly increased risk for cirrhosis (adjusted odds ratio 1.6, 95%
      confidence interval 1.1-2.3), especially among Black patients (adjusted odds
      ratio 2.9, 95% confidence interval 1.6-5.2). In addition, among HIV/HCV
      coinfected patients, longer cumulative exposures to all antiretroviral
      medications, all nucleoside reverse transcriptase inhibitors, all protease
      inhibitors, and selected individual medications (didanosine, stavudine, and
      nelfinavir) were found to be significantly associated with cirrhosis. In
      contrast, among HIV-infected patients not coinfected with HCV (245 with cirrhosis
      and 658 matched controls), HALS or exposure to antiretroviral medications was
      found not to be significantly associated with cirrhosis, with the exception of
      didanosine. CONCLUSION: HALS and cumulative exposure to nucleoside reverse
      transcriptase inhibitors and protease inhibitors, especially stavudine,
      didanosine, and nelfinavir, were found to be associated with the development of
      cirrhosis in HIV/HCV coinfected patients, but not in HIV-monoinfected patients.

PMID- 25769097
TI  - Prevalence and correlates of HCV monoinfection and HIV and HCV coinfection among
      persons who inject drugs in Vietnam.
AB  - BACKGROUND: Vietnam bears a high burden of hepatitis C virus (HCV) and HIV
      infection among persons who inject drugs (PWID). The high prevalence of HCV and
      HIV occurs in a context of stigma and limited preventive interventions for PWID.
      OBJECTIVES: This study aims to estimate the prevalence of HCV, HIV, and HIV/HCV
      coinfection among PWID and to explore their associations with lifetime injection
      behaviors. METHODS: A total of 1434 PWID were recruited from the Thai Nguyen
      Province of Vietnam between 2005 and 2007. Participants responded to a structured
      questionnaire and provided blood samples at baseline. A cross-sectional analysis
      of data collected at baseline was carried out. Factors associated with HCV
      monoinfection and HIV/HCV coinfection were evaluated by multinomial logistic
      regression. RESULTS: The prevalences of HIV and HCV were 35.1 and 88.8%,
      respectively, and the prevalences of HIV/HCV coinfection and HCV monoinfection
      were 34.8 and 53.9%, respectively. After adjusting for confounders in
      multivariate analysis, ever reusing a syringe and needle was found to be
      significantly associated with HIV monoinfection [adjusted odds ratio (AOR), 3.13;
      95% confidence interval (CI), 1.99-4.94] and HIV/HCV coinfection (AOR, 3.34; 95%
      CI, 2.02-5.51). Ever sharing diazepam or novocaine was also found to be
      significantly associated with HIV monoinfection (AOR, 2.14; 95% CI, 1.38-3.32)
      and HIV/HCV coinfection (AOR, 2.47; 95% CI, 1.57-3.90). CONCLUSION: Our findings
      demonstrate a high burden of HIV and HCV infection among PWID in Vietnam.
      Lifetime injection behaviors, including sharing of diazepam or novocaine, may
      account for the high prevalence of HIV and HCV. Improving prevention and ensuring
      access to care remain critically important for this vulnerable population.

PMID- 25769098
TI  - De-novo portal vein thrombosis in liver cirrhosis: risk factors and correlation
      with the Model for End-stage Liver Disease scoring system.
AB  - BACKGROUND AND OBJECTIVES: Portal vein thrombosis (PVT) is a potential lethal
      complication in late liver cirrhosis. There is a lack of knowledge of the
      clinical features and risk factors of PVT. We aimed to investigate the clinical
      and radiological characteristics, and biochemical markers of cirrhotic patients
      to determine the high-risk individuals for PVT attending our center. PATIENTS AND
      METHODS: Of 426 cirrhotic patients, only 120 consecutive patients were included.
      Clinical, biochemical, immunological, Model for End-stage Liver Disease (MELD)
      score, portal vein patency, and flow velocity were measured in all patients at
      baseline and every 6 months thereafter. Variables that could predict the
      development of PVT within 1 year were identified by multiple logistic regression.
      RESULTS: Only 95 patients completed the study; PVT was found in 17 (17.9%)
      patients. PVT was observed mainly in the portal trunk, superior mesenteric vein,
      and splenic vein. Univariate analysis showed that diabetes mellitus, lower levels
      of hemoglobin, platelet counts, and portal vein flow velocity as well as
      increased MELD scores, platelet indices, portal vein diameter, and splenic
      thickness were associated with PVT patients than in non-PVT patients (all
      P<0.01). CONCLUSION: The incidence of PVT was 17.9%. PVT occurred mainly in the
      portal vein trunk, superior mesenteric vein, and splenic vein. Diabetes mellitus,
      lower levels of hemoglobin, platelet count and portal vein flow velocity as well
      as increased MELD score, platelet indices, portal vein diameter, and splenic
      thickening were associated with PVT. Splenic thickening, marked reduced of mean
      portal flow velocity, and diabetes mellitus may be risk factors for PVT.

PMID- 25769099
TI  - Novel ENAM and LAMB3 mutations in Chinese families with hypoplastic amelogenesis
      imperfecta.
AB  - Amelogenesis imperfecta is a group of inherited diseases affecting the quality
      and quantity of dental enamel. To date, mutations in more than ten genes have
      been associated with non-syndromic amelogenesis imperfecta (AI). Among these,
      ENAM and LAMB3 mutations are known to be parts of the etiology of hypoplastic AI
      in human cases. When both alleles of LAMB3 are defective, it could cause
      junctional epidermolysis bullosa (JEB), while with only one mutant allele in the
      C-terminus of LAMB3, it could result in severe hypoplastic AI without skin
      fragility. We enrolled three Chinese families with hypoplastic autosomal-dominant
      AI. Despite the diagnosis falling into the same type, the characteristics of
      their enamel hypoplasia were different. Screening of ENAM and LAMB3 genes was
      performed by direct sequencing of genomic DNA from blood samples. Disease-causing
      mutations were identified and perfectly segregated with the enamel defects in
      three families: a 19-bp insertion mutation in the exon 7 of ENAM
      (c.406_407insTCAAAAAAGCCGACCACAA, p.K136Ifs*16) in Family 1, a single-base
      deletion mutation in the exon 5 of ENAM (c. 139delA, p. M47Cfs*11) in Family 2,
      and a LAMB3 nonsense mutation in the last exon (c.3466C>T, p.Q1156X) in Family 3.
      Our results suggest that heterozygous mutations in ENAM and LAMB3 genes can cause
      hypoplastic AI with markedly different phenotypes in Chinese patients. And these
      findings extend the mutation spectrum of both genes and can be used for mutation
      screening of AI in the Chinese population. 

PMID- 25769100
TI  - Analysis of relative concentration of ethanol and other odorous compounds (OCs)
      emitted from the working surface at a landfill in China.
AB  - Estimating odor emissions from landfill sites is a complicated task because of
      the various chemical and biological species that exist in landfill gases. In this
      study, the relative concentration of ethanol and other odorous compounds emitted
      from the working surface at a landfill in China was analyzed. Gas sampling was
      conducted at the landfill on a number of selected days from March 2012 to March
      2014, which represented different periods throughout the two years. A total of
      41, 59, 66, 54, 63, 54, 41, and 42 species of odorous compounds were identified
      and quantified in eight sampling activities, respectively; a number of 86 species
      of odorous compounds were identified and quantified all together in the study.
      The measured odorous compounds were classified into six different categories
      (Oxygenated compounds, Halogenated compounds, Terpenes, Sulfur compounds,
      Aromatics, and Hydrocarbons). The total average concentrations of the oxygenated
      compounds, sulfur compounds, aromatics, halogenated compounds, hydrocarbons, and
      terpenes were 2.450 mg/m3, 0.246 mg/m3, 0.203 mg/m3, 0.319 mg/m3, 0.530 mg/m3,
      and 0.217 mg/m3, respectively. The relative concentrations of 59 odorous
      compounds with respect to the concentration of ethyl alcohol (1000 ppm) were
      determined. The dominant contaminants that cause odor pollution around the
      landfill are ethyl sulfide, methyl mercaptan, acetaldehyde, and hydrogen sulfide;
      dimethyl disulfide and dimethyl sulfide also contribute to the pollution to a
      certain degree. 

PMID- 25769102
TI  - The toxicological impacts of some heavy metals on carbonic anhydrase from
      gilthead sea bream (Sparus aurata) gills.
AB  - It is known that heavy metals have toxic effects on fish. Insufficient measures
      are a serious problem in our country and around the world. This problem can
      threaten human health in areas where it is common for people to obtain nutrition
      from local bodies of water. In this study, the toxicological impacts of some
      heavy metals were investigated on carbonic anhydrase activity in gilthead gills.
      Carbonic anhydrase (CA) was purified from gilthead sea bream (Sparus aurata)
      gills with a specific activity of 2872.92 EU mg(-1) and a yield of 32.84% using
      affinity chromatography. The overall purification was approximately ~ 84-fold.
      SDS-polyacrylamide gel electrophoresis showed a single band, and the MW was
      approximately 30.5 kDa (Soyut et al., 2008, 2012; Soyut and Beydemir, 2008, 2012;
      Kaya et al., 2013). The kinetic and characteristic properties of CA such as the
      optimum pH, stable pH, optimum temperature, activation energy (Ea), activation
      enthalpy (DeltaH), Q10, Km and Vmax were determined. Cadmium (Cd(2+)), copper
      (Cu(2+)), nickel (Ni(2+)) and silver (Ag(+)) inhibited CA activity in in vitro
      conditions. Ki values were calculated for these metals. Ki values were 31.20mM
      for cadmium (Cd(2+)), 161.96 mM for copper (Cu(2+)), 10.79 mM for nickel (Ni(2+))
      and 0.0082 mM for silver (Ag(+)) based on Lineweaver-Burk plots. Except for
      cadmium, heavy metals had the same inhibition mechanism. Cadmium was competitive,
      and the others were noncompetitive.

PMID- 25769101
TI  - Modulation of cell metabolic pathways and oxidative stress signaling contribute
      to acquired melphalan resistance in multiple myeloma cells.
AB  - Alkylating agents are widely used chemotherapeutics in the treatment of many
      cancers, including leukemia, lymphoma, multiple myeloma, sarcoma, lung, breast
      and ovarian cancer. Melphalan is the most commonly used chemotherapeutic agent
      against multiple myeloma. However, despite a 70-80% initial response rate,
      virtually all patients eventually relapse due to the emergence of drug-resistant
      tumour cells. By using global proteomic and transcriptomic profiling on melphalan
      sensitive and resistant RPMI8226 cell lines followed by functional assays, we
      discovered changes in cellular processes and pathways not previously associated
      with melphalan resistance in multiple myeloma cells, including a metabolic switch
      conforming to the Warburg effect (aerobic glycolysis), and an elevated oxidative
      stress response mediated by VEGF/IL8-signaling. In addition, up-regulated aldo
      keto reductase levels of the AKR1C family involved in prostaglandin synthesis
      contribute to the resistant phenotype. Finally, selected metabolic and oxidative
      stress response enzymes were targeted by inhibitors, several of which displayed a
      selective cytotoxicity against the melphalan-resistant cells and should be
      further explored to elucidate their potential to overcome melphalan resistance. 

PMID- 25769103
TI  - PM10 in a background urban site: chemical characteristics and biological effects.
AB  - PM10 was sampled in a background urban site in Torino, a northern Italian city.
      PM10 extracts were tested with THP-1 and A-549 cells to evaluate their effects on
      cell proliferation, LDH activity, TNFalpha, IL8 and CYP1A1 expression, and
      genotoxic damage induction (Comet assay). Through Principal Component Analysis
      (PCA), it was observed that (1) the aqueous extracts induced the inhibition of
      cell proliferation in the warm season that clustered together to total ions, (2)
      organic extracts determined a winter cell viability reduction and (3) there was a
      genotoxic effect associated with PAH and metal concentrations. The analysed low
      PAH levels were unable to induce significant CYP1A1 expression. The results
      obtained confirmed that PM composition and seasonality play an important role in
      particle-induced toxicity. The presence of PM10-induced biological effects at a
      low polluted site suggested that a reduction of PM10 mass did not seem to be
      sufficient to reduce its toxicity. 

PMID- 25769104
TI  - Organic extracts from African dust storms stimulate oxidative stress and induce
      inflammatory responses in human lung cells through Nrf2 but not NF-kappaB.
AB  - The health impact of the global African dust event (ADE) phenomenon in the
      Caribbean has been vaguely investigated. Heavy metals in ADE and non-ADE extracts
      were evaluated for the formation of reactive oxygen species (ROS) and antioxidant
      capacity by cells using, deferoxamine mesylate (DF) and N-acetyl-l-cysteine
      (NAC). Results show that ADE particulate matter 2.5 (PM2.5) induces ROS and
      stimulates oxidative stress. Pre-treatment with DF reduces ROS in ADE and Non-ADE
      extracts and in lung cells demonstrating that heavy metals are of utmost
      importance. Glutathione-S-transferase and Heme Oxygenase 1 mRNA levels are
      induced with ADE PM and reduced by DF and NAC. ADE extracts induced Nrf2 activity
      and IL-8 mRNA levels significantly more than Non-ADE. NF-kappaB activity was not
      detected in any sample. Trace elements and organic constituents in ADE PM2.5
      enrich the local environment load, inducing ROS formation and activating
      antioxidant-signaling pathways increasing pro-inflammatory mediator expressions
      in lung cells. 

PMID- 25769105
TI  - Concentration-dependent effect of photoluminescent carbon dots on the microbial
      activity of the soil studied by combination methods.
AB  - Carbon dots (Cdots) have a great potential for their widespread biological
      applications. However, there are a few studies on the biosafety of Cdots. In this
      work, the biological effect of Cdots on soil microorganism was analyzed by
      microcalorimetry, soil enzymatic activities, and denaturing gradient gel
      electrophoresis (DGGE). The addition of Cdots causes a gradual increase of the
      maximum heat power (P peak) and the growth rate (k) at low concentration of Cdots
      (0.0-50.00 MUg/g). But there is no significant effect of Cdots on the total heat
      output (Q total). The urease and fluorescein diacetate esterase activities
      demonstrate that introduction of Cdots to soil has almost no impact on the
      structure and function of the soil microbial community and microbial processes.
      The DGGE results exhibit that the control and the Cdots-treated soils display
      similar patterns, indicating that Cdots have little effect on the microbial
      community structure.

PMID- 25769106
TI  - Does higher income inequality adversely influence infant mortality rates?
      Reconciling descriptive patterns and recent research findings.
AB  - As the struggle continues to explain the relatively high rates of infant
      mortality (IMR) exhibited in the United States, a renewed emphasis is being
      placed on the role of possible 'contextual' determinants. Cross-sectional and
      short time-series studies have found that higher income inequality is associated
      with higher IMR at the state level. Yet, descriptively, the longer-term trends in
      income inequality and in IMR seem to call such results into question. To assess
      whether, over the period 1990-2007, state-level income inequality is associated
      with state-level IMR; to examine whether the overall effect of income inequality
      on IMR over this period varies by state; to test whether the association between
      income inequality and IMR varies across this time period. IMR data--number of
      deaths per 1000 live births in a given state and year--were obtained from the
      U.S. Centers for Disease Control Wonder database. Income inequality was measured
      using the Gini coefficient, which varies from zero (complete equality) to 100
      (complete inequality). Covariates included state-level poverty rate, median
      income, and proportion of high school graduates. Fixed and random effects
      regressions were conducted to test hypotheses. Fixed effects models suggested
      that, overall, during the period 1990-2007, income inequality was inversely
      associated with IMR (beta = -0.07, SE (0.01)). Random effects models suggested
      that when the relationship was allowed to vary at the state-level, it remained
      inverse (beta = -0.05, SE (0.01)). However, an interaction between income
      inequality and time suggested that, as time increased, the effect of income
      inequality had an increasingly positive association with total IMR (beta = 0.009,
      SE (0.002)). The influence of state income inequality on IMR is dependent on
      time, which may proxy for time-dependent aspects of societal context.

PMID- 25769108
TI  - Moving beyond local practice: reconfiguring the adoption of a breast cancer
      diagnostic technology.
AB  - This paper explores the ways in which technological innovation becomes adopted
      and incorporated into healthcare practice. Drawing upon the notion of 'field of
      practices', we examine how adoption is subject to spatially and temporally
      distributed reconfigurations across a multi-level set of practices, ranging from
      the policy level to the micro-level setting of individual action. The empirical
      backdrop is provided by a case study of the adoption of Breast Lymph Node Assay
      (BLNA), a diagnostic technology innovation for the treatment of breast cancer
      patients. Our aim is to contribute to the development of a more comprehensive
      analysis of the processes surrounding the adoption and incorporation of complex
      healthcare technologies into routine practice. 

PMID- 25769107
TI  - Increase of perceived frequency of neighborhood domestic violence is associated
      with increase of women's depression symptoms in a nationally representative
      longitudinal study in South Africa.
AB  - Studies that examine the effects of neighborhood characteristics on mental health
      show that perceptions of general neighborhood violence are associated with
      depression across diverse populations (Clark et al., 2008; Velez-Gomez et al.,
      2013; Wilson-Genderson & Pruchno, 2013). However, to our knowledge, none have
      examined the specific effect of perceived frequency of neighborhood domestic
      violence (PFNDV) on residents' mental health, despite knowledge that domestic
      violence is a potent predictor of depression at the level of the individual. This
      study investigates the impact of PFNDV on mental health using the South African
      National Income Dynamics Study (SA-NIDS). NIDS Waves 2 and 3 measure the
      perceived frequency of six neighborhood violence subtypes through the NIDS
      household respondent questionnaire and depression through a questionnaire
      administered to all NIDS participants. Linear regression was used to model the
      relationship between change in depression symptoms and change in violence
      subtypes between Waves 2 and 3. We found that two-year increase in PFNDV was
      significantly correlated with increase of depression symptoms over the same time
      period for women, independently of individual, household and neighborhood level
      characteristics, including five other types of neighborhood violence. No other
      type of violence was associated with increased depression in women in the fully
      adjusted model. Research and policy implications are discussed. 

PMID- 25769109
TI  - Correlates of depressive symptoms among North Korean refugees adapting to South
      Korean society: the moderating role of perceived discrimination.
AB  - Although the prevalence of depressive disorders among North Korean (NK) refugees
      living in South Korea has been reported to be twice the rate of their South
      Korean counterparts, little is known about the correlates of depressive symptoms
      among this population. Despite their escape from a politically and economically
      repressive setting, NK refugees continue to face multidimensional hardships
      during their adaptation process in South Korea, which can adversely affect their
      mental health. However, to our knowledge, no empirical research exists to date on
      depressive symptoms in the context of adaptation or perceived discrimination
      among NK refugees. To fill this gap, this study used a sample of 261 NK refugees
      in South Korea from the 2010 National Survey on Family Violence to examine
      associations between sociocultural adaptation, perceived discrimination, and
      depressive symptoms, as well as the moderation effect of discrimination on
      adaptation to depressive symptoms. We found that poor sociocultural adaptation
      and perception of discrimination were associated with increased levels of
      depressive symptoms. Perception of discrimination attenuated the association
      between better adaptation and fewer depressive symptoms, when compared to no
      perception of discrimination. These findings highlight the need to improve NK
      refugees' adaptation and integration as well as their psychological well-being in
      a culturally sensitive and comprehensive manner. They also underscore the
      importance of educating South Koreans to become accepting hosts who value
      diversity, yet in a homogeneous society. 

PMID- 25769110
TI  - Obesity triggers enhanced MDSC accumulation in murine renal tumors via elevated
      local production of CCL2.
AB  - Obesity is one of the leading risk factors for developing renal cell carcinoma,
      an immunogenic tumor that is treated clinically with immunostimulatory therapies.
      Currently, however, the mechanisms linking obesity with renal cancer incidence
      are unclear. Using a model of diet-induced obesity, we found that obese BALB/c
      mice with orthotopic renal tumors had increased total frequencies of myeloid
      derived suppressor cells (MDSC) in renal tumors and spleens by d14 post-tumor
      challenge, relative to lean counterparts. Renal tumors from obese mice had
      elevated concentrations of the known myeloid cell chemoattractant CCL2, which was
      produced locally by increased percentages of dendritic cells, macrophages, B
      cells, and CD45- cells in tumors. MDSC expression of the CCL2 receptor, CCR2, was
      unaltered by obesity but greater percentages of CCR2+ MDSCs were present in renal
      tumors from obese mice. Of note, the intracellular arginase levels and per-cell
      suppressive capacities of tumor-infiltrating and splenic MDSCs were unchanged in
      obese mice relative to lean controls. Thus, our findings suggest that obesity
      promotes renal tumor progression via development of a robust immunosuppressive
      environment that is characterized by heightened local and systemic MDSC
      prevalence. Targeted intervention of the CCL2/CCR2 pathway may facilitate immune
      mediated renal tumor clearance in the obese. 

PMID- 25769111
TI  - Mixed heterolobosean and novel gregarine lineage genes from culture ATCC 50646:
      Long-branch artefacts, not lateral gene transfer, distort alpha-tubulin
      phylogeny.
AB  - Contradictory and confusing results can arise if sequenced 'monoprotist' samples
      really contain DNA of very different species. Eukaryote-wide phylogenetic
      analyses using five genes from the amoeboflagellate culture ATCC 50646 previously
      implied it was an undescribed percolozoan related to percolatean flagellates
      (Stephanopogon, Percolomonas). Contrastingly, three phylogenetic analyses of 18S
      rRNA alone, did not place it within Percolozoa, but as an isolated deep-branching
      excavate. I resolve that contradiction by sequence phylogenies for all five genes
      individually, using up to 652 taxa. Its 18S rRNA sequence (GQ377652) is near
      identical to one from stained-glass windows, somewhat more distant from one from
      cooling-tower water, all three related to terrestrial actinocephalid gregarines
      Hoplorhynchus and Pyxinia. All four protein-gene sequences (Hsp90; alpha-tubulin;
      beta-tubulin; actin) are from an amoeboflagellate heterolobosean percolozoan, not
      especially deeply branching. Contrary to previous conclusions from trees
      combining protein and rRNA sequences or rDNA trees including Eozoa only, this
      culture does not represent a major novel deep-branching eukaryote lineage
      distinct from Heterolobosea, and thus lacks special significance for deep
      eukaryote phylogeny, though the rDNA sequence is important for gregarine
      phylogeny. alpha-Tubulin trees for over 250 eukaryotes refute earlier suggestions
      of lateral gene transfer within eukaryotes, being largely congruent with
      morphology and other gene trees.

PMID- 25769112
TI  - HPV clearance and the neglected role of stochasticity.
AB  - Clearance of anogenital and oropharyngeal HPV infections is attributed primarily
      to a successful adaptive immune response. To date, little attention has been paid
      to the potential role of stochastic cell dynamics in the time it takes to clear
      an HPV infection. In this study, we combine mechanistic mathematical models at
      the cellular level with epidemiological data at the population level to
      disentangle the respective roles of immune capacity and cell dynamics in the
      clearing mechanism. Our results suggest that chance-in form of the stochastic
      dynamics of basal stem cells-plays a critical role in the elimination of HPV
      infected cell clones. In particular, we find that in immunocompetent adolescents
      with cervical HPV infections, the immune response may contribute less than 20% to
      virus clearance-the rest is taken care of by the stochastic proliferation
      dynamics in the basal layer. In HIV-negative individuals, the contribution of the
      immune response may be negligible. 

PMID- 25769113
TI  - Persistence assessment of cyclohexyl- and norbornyl-derived ketones and their
      degradation products in different OECD screening tests.
AB  - The persistence of synthetic cyclohexyl- and norbornyl-derived ketones was
      assessed by using OECD 301F and 301D biodegradation tests. While cyclohexyl
      derived ketones either reached or came close to the pass level (60%) after 60 d,
      the corresponding norbornyl derivatives yielded significantly less biodegradation
      (<40%). By analyzing extracts at 60 d, the key degradation products of four
      norbornyl derivatives were identified. Consistently, 2-bicyclo[2.2.1]heptane
      carboxylic acid was found as a principal degradation product with minor
      quantities of bicyclo[2.2.1]heptan-2-one and 2-bicyclo[2.2.1]heptane acetic acid.
      When the three degradation products were re-synthesized and tested individually
      for biodegradability, the former two were found to be ultimately biodegradable
      after 60 d in OECD 301D tests, thus proving non-persistence. Similarly, 2
      bicyclo[2.2.1]heptane acetic acid was found to be degraded significantly, albeit
      with long lag phases exceeding 60 d in the case of freshwater inoculum, then
      ultimately reaching the pass level. On the other hand, norbornyl ketones were
      still only partially biodegradable in the same test. We conclude that despite the
      potential for ultimate biodegradation of norbornyl-derived ketones, current
      screening tests yield an incomplete picture of their biodegradability,
      particularly when applying strict OECD criteria. The appearance of long lag
      phases when re-testing norbornyl ketone degradation products underlines the
      importance of extending tests to well beyond 28 and even 60 d in the case of
      freshwater inocula.

PMID- 25769114
TI  - The older, the wider: On-field tactical behavior of elite-standard youth soccer
      players in small-sided games.
AB  - PURPOSE: Young soccer players need excellent tactical skills to reach the top.
      Tactical behavior emerges through interactions between opposing teams. However,
      few studies have focused on on-field tactical behavior of teams with talented
      soccer players. Therefore, this study aimed to determine teams' tactical behavior
      during small-sided games in two age categories, Under-17 and Under-19. METHODS:
      Positional data of thirty-nine elite-standard soccer players were collected
      during twenty-four small-sided games to calculate longitudinal and lateral inter
      team distances, stretch indices and length per width ratios. Corresponding
      interaction patterns and game-to-game variability were also determined. RESULTS:
      Under-19 showed a significantly larger lateral stretch index and a significantly
      lower length per width ratio compared with Under-17. Furthermore, teams of both
      age groups showed similar large proportions of in-phase behavior. Variability of
      tactical performance measures within and between games was similar for Under-17
      and Under-19. CONCLUSIONS: Variability within games seems to be functional for
      attacking teams for creating goal-scoring opportunities. In conclusion, the main
      difference was that Under-19 adopted a wider pitch dispersion than Under-17,
      represented by a larger lateral stretch index and smaller length per width ratio.
      Coach instructions and training exercises should be directed at exploiting pitch
      width to increase the pursuit of goal-scoring.

PMID- 25769115
TI  - Different assessment tasks produce different estimates of handedness stability
      during the eight to 14 month age period.
AB  - Using 150 infants (57% males), two common tasks for assessing infant hand-use
      preferences for acquiring objects were compared for their ability to detect
      stable preferences during the age period of eight to 14 months. One task assesses
      the preference using nine presentations of objects; the other uses 32
      presentations. Monthly classifications of hand preference for each task were
      determined by either a commonly used a decision criterion in which one hand is
      used 50% more often than the other or a criterion based on proportion of hand-use
      difference that exceeds a conventional alpha probability of 0.05. The seven
      monthly assessments provided by the two tasks also were examined for latent
      classes in their developmental trajectories. The two tasks were significantly
      different for both their identification of latent classes and their monthly
      classification of the infant's hand-use preference. The 32 presentations yielded
      three developmental trajectories (45% right preferring, 5% left preferring, and
      50% no clear preference) whereas the nine presentations revealed only two
      trajectories (70% right, 30% no preference). The nine presentations task, with
      the 50% proportion decision criterion, was very generous in classifying right and
      left-preferring infants at each month but produced greater fluctuations across
      months compared to the 32 presentation task with an alpha decision criterion.
      Both tasks revealed that a large proportion of infants are still developing a
      hand-use preference during this age period. Recommendations are made for
      examining the development of hand-use preferences and their relation to the
      development of other neuropsychological functions. 

PMID- 25769116
TI  - A fit for purpose training programme for the decontamination of personnel.
AB  - Contingency plans are a crucial part of operating any nuclear facility. The
      success of a contingency plan depends on the efficacy of the plan and the
      confidence and understanding of those who must enact it. This project focused on
      both of these aspects, clarifying technique and then designing and delivering a
      training programme for decontamination. The design of the training was based on
      the IAEA Systematic Approach to Training (SAT). The delivery focused on ways of
      increasing retention including use of practical examples and assessment, peer
      assessment and visual contingency plans. A quantitative survey of the trainees
      was conducted using a questionnaire before and after the training programme
      delivery. The results clearly demonstrate an improvement across all elements of
      skills and knowledge required to undertake decontamination. Effective training is
      fundamental to the development of a good safety culture and the methodology used
      in this work has led to a clear improvement in radiation protection culture at
      the Devonport site. 

PMID- 25769118
TI  - Erratum.

PMID- 25769117
TI  - Missing upper incisors: a retrospective study of orthodontic space closure versus
      implant.
AB  - BACKGROUND: The aim of this retrospective study was to compare the esthetic,
      periodontal, and functional outcomes of orthodontic space closure versus implant
      substitution in patients with missing maxillary incisors 5 years after completion
      of treatment. METHODS: The study group consisted of ten patients treated with
      orthodontic space closure (six males, four females, mean age 19 +/- 2.1 years at
      the completion of treatment) and ten patients treated with implant insertion
      (five males, five females, mean age 20 +/- 1.4 years at the time of implant
      insertion). Tooth mobility, plaque index, probing depth, infraocclusion, open
      gingival embrasure (black triangle), and temporomandibular joint function were
      recorded at the 5.6 years follow-up. Self-perceived dental esthetic appearance
      was also evaluated through a visual analog scale (VAS) questionnaire. T-test was
      used to evaluate the data. RESULTS: All patients were equally satisfied with the
      appearance of their teeth 5.6 +/- 0.4 years after the completion of treatment. No
      statistically significant differences were found in relation to the VAS scores of
      the subjects (P < 0.857). No significant differences were found in tooth
      mobility, plaque index (P < 0.632), and the prevalence of signs and symptoms of
      temporomandibular disorders. However, significant infraocclusion was noticed in
      all implant patients (P < 0.001). Probing depth was also significantly higher in
      implant patients (P < 0.001). CONCLUSIONS: Orthodontic space closure and implant
      of missing maxillary incisors produced similar, well-accepted esthetic results.
      None of the treatments impaired temporomandibular joint function. Nevertheless,
      infraocclusion was evident in implant patients. Space closure patients also
      showed better periodontal health in comparison with implant patients.

PMID- 25769120
TI  - Activin A in perinatal brain injury.
AB  - Activin A is a multifunctional growth and differentiation factor belonging to the
      transforming growth factor beta (TGF-beta) family. Growing evidence indicates its
      role as a neurotrophic factor and regulator of synaptic transmission as well as
      its functional importance in several types of cerebral injury. We recently
      described age-dependent expression of activin A and its regulation at the mRNA
      and protein level under different conditions of global hypoxia in the neonatal
      mouse brain. This review discusses the current knowledge of the function and
      regulation of activin A from human studies as well as from experimental models of
      brain injury focusing on acquired lesions of the developing rodent brain during
      the early stages of brain maturation. 

PMID- 25769119
TI  - Loss of pdr-1/parkin influences Mn homeostasis through altered ferroportin
      expression in C. elegans.
AB  - Overexposure to the essential metal manganese (Mn) can result in an irreversible
      condition known as manganism that shares similar pathophysiology with Parkinson's
      disease (PD), including dopaminergic (DAergic) cell loss that leads to motor and
      cognitive impairments. However, the mechanisms behind this neurotoxicity and its
      relationship with PD remain unclear. Many genes confer risk for autosomal
      recessive, early-onset PD, including the parkin/PARK2 gene that encodes for the
      E3 ubiquitin ligase Parkin. Using Caenorhabditis elegans (C. elegans) as an
      invertebrate model that conserves the DAergic system, we previously reported
      significantly increased Mn accumulation in pdr-1/parkin mutants compared to
      wildtype (WT) animals. For the current study, we hypothesize that this enhanced
      accumulation is due to alterations in Mn transport in the pdr-1 mutants. While no
      change in mRNA expression of the major Mn importer proteins (smf-1-3) was found
      in pdr-1 mutants, significant downregulation in mRNA levels of the putative Mn
      exporter ferroportin (fpn-1.1) was observed. Using a strain overexpressing fpn
      1.1 in worms lacking pdr-1, we show evidence for attenuation of several endpoints
      of Mn-induced toxicity, including survival, metal accumulation, mitochondrial
      copy number and DAergic integrity, compared to pdr-1 mutants alone. These changes
      suggest a novel role of pdr-1 in modulating Mn export through altered transporter
      expression, and provides further support of metal dyshomeostasis as a component
      of Parkinsonism pathophysiology. 

PMID- 25769121
TI  - Synthesis, spectral characterization and density functional theory exploration of
      1-(quinolin-3-yl)piperidin-2-ol.
AB  - The experimental and theoretical vibrational frequencies of a newly synthesized
      compound, namely 1-(quinolin-3-yl)piperidin-2-ol (QPPO) are analyzed. The
      experimental FT-IR (4000-400 cm(-1)) and FT-Raman (4000-100 cm(-1)) of the
      molecule in solid phase have been recorded. The optimized molecular structure,
      vibrational assignments of QPPO have been investigated experimentally and
      theoretically using Gaussian03W software package. The stability of the molecule
      arising from hyper-conjugative interaction and charge delocalization has been
      analyzed using NBO analysis. The first order hyperpolarizability (beta0) is
      calculated to find its character in non-linear optics. Gauge including atomic
      orbital (GIAO) method is used to calculate (1)H NMR chemical shift calculations
      were carried out and compared with experimental data. The electronic properties
      like UV-Visible spectral analysis and HOMO-LUMO energies were reported. The
      energy gap shows that the charge transfer occurs within the molecule.
      Thermodynamic parameters of the title compound were calculated at various
      temperatures.

PMID- 25769122
TI  - Size controlled biogenic silver nanoparticles as antibacterial agent against
      isolates from HIV infected patients.
AB  - Silver nanoparticles (AgNPs) are synthesized using biological sources due to its
      high specificity in biomedical applications. Herein, we report the size and shape
      controlled synthesis of AgNPs using the aqueous extract of blue green alga,
      Spirulina platensis. Size, shape and elemental composition of AgNPs were
      characterized using UV-vis spectroscopy, Fluorescence spectroscopy, FT-IR
      (Fourier Transform-Infrared Spectroscopy), FT-RS (Fourier Transform-Raman
      Spectroscopy), SEM-EDAX (Scanning Electron Microscopy-Energy Dispersive X-ray
      analysis) and HR-TEM (High Resolution Transmission Electron Microscopy). AgNPs
      were stable, well defined and monodispersed (spherical) with an average size of 6
      nm. The synthesized AgNPs were tested for its antibacterial potency against
      isolates obtained from HIV patients.

PMID- 25769123
TI  - The influence of the long-range order on the vibrational spectra of structures
      based on sodalite cage.
AB  - Zeolites are a group of tecto-aluminosilicates with numerous practical
      applications, e.g. gas separators, molecular sieves and sorbents. The unique
      properties result from porous structure of channels and cages which are built
      from smaller units - the so-called Secondary Building Units (SBU), and sometimes
      also larger groups (Breck, 1974; Ciciszwili et al., 1974; Mozgawa, 2008; Cejka
      and van Bekkum, 2005). The aim of this study was the examination of the influence
      of long-range order on vibrational spectra of sodalite and zeolite A. Ab initio
      calculations (geometry optimizations and vibrational spectra calculations) of
      sodalite cage and selected SBU were carried out by means of Gaussian09 (Frisch et
      al., 2009) (in the case of isolated clusters) and Crystal09 (Dovesi et al., 2005,
      2009) (for periodic structures). The obtained results were compared with the
      experimental spectra of sodalite and zeolite A crystal structures, synthesized
      under hydrothermal conditions. These results allowed analyzing of the long-range
      ordering influence on the vibrational spectra, as well as the identification of
      the characteristic vibrations in beta cage based frameworks. It has been found,
      that based on small structural fragment (SBU) models a characteristic vibrations
      can be identify. However, full spectra analysis and especially the interpretation
      of far-infrared region of the spectra require using periodic models under the
      influence of translational crystal lattice. 

PMID- 25769124
TI  - Time trends of polybrominated diphenylether (PBDE) congeners in serum of Swedish
      mothers and comparisons to breast milk data.
AB  - In the present study our main focus was blood serum levels and time trends of the
      fully brominated diphenyl ether (PBDE) BDE-209 in Swedish first-time mothers, as
      relatively a few human data on this congener are currently available. Also,
      levels and temporal trends in serum of other more commonly reported PBDE
      congeners and HBCD were studied. In an ongoing study on POPs in Uppsala
      Primiparas (POPUP), serum samples (N=413) from first-time mothers from 1996 to
      2010 were used. Pooling of individual samples (5-25 individuals/pool, approx. 3
      pools/year) resulted in 36 pooled samples used for PBDE/HBCD analysis on GC-LRMS.
      In addition, serum/breast milk correlations for PBDE and HBCD levels in 30 paired
      samples from individual mothers sampled 2010 were studied. The mean serum level
      of BDE-209 (1.3ng/g lipid wt.) was highest of all studied PBDE congeners,
      followed by BDE-47 and BDE-153. There was no significant temporal trend for BDE
      209 during the study period, whereas the levels of BDE-47, BDE-99, BDE-100 and of
      HBCD decreased significantly in pooled serum 1996-2010. After omission of one
      outlier, a significant increasing trend was observed for BDE-153. The serum/milk
      PBDE quotients in paired individual samples from 2010 ranged from 0.83 to 17,
      with the highest quotient for BDE-209. Differences in PBDE transfer from blood to
      milk are probably related to molecular weight or size. The correlations between
      serum and milk levels of tetra- to hexa-brominated congeners were generally
      strong (r=0.83-0.97), but weaker for BDE-183 (r=0.57) and BDE-209 (r=0.38).
      Regarding HBCD, serum levels in 2010 were mostly beneath LOQ which made
      serum/milk quotients impossible. The decreasing levels of some BFR compounds in
      serum over time show that exposures have decreased after the production and use
      of some of these substances have been restricted. The lack of temporal trend of
      BDE-209 suggests that the human exposure to this congener in Sweden has been
      stable for more than a decade. 

PMID- 25769125
TI  - Tracking the sources of polybrominated diphenyl ethers in birds: foraging in
      waste management facilities results in higher DecaBDE exposure in males.
AB  - Differences in feeding ecology are now recognized as major determinants of inter
      individual variations in contaminant profiles of free-ranging animals, but
      exceedingly little attention has been devoted to the role of habitat use. Marked
      inter-individual variations and high levels of polybrominated diphenyl ethers
      (PBDEs) (e.g., DecaBDE) have previously been documented in ring-billed gulls
      (Larus delawarensis) breeding in a colony near Montreal (QC, Canada). However,
      the environmental sources of these compounds, and thus the reasons causing these
      large inter-individual variations remain unidentified. In the present study, we
      used GPS-based telemetry (+/-5 to 10m precision) to track ring-billed gulls from
      this colony to reconstruct their movements at the landscape level. We related
      habitat use of individual gulls (n=76) to plasma concentrations (ng/g ww) and
      relative contributions (percentages) to Sigma38PBDEs of major congeners in the
      internationally restricted PentaBDE and current-use DecaBDE mixtures. Male gulls
      that visited waste management facilities (WMFs; i.e., landfills, wastewater
      treatment plants and related facilities; 25% of all GPS-tracked males) exhibited
      greater DecaBDE (concentrations and percentages) and lower PentaBDE (percentages)
      relative to those that did not. In contrast, no such relationships were found in
      females. Moreover, in males, DecaBDE (concentrations and percentages) increased
      with percentages of time spent in WMFs (i.e., ~5% of total foraging time), while
      PentaBDE (percentages) decreased. No relationships between percentages of time
      spent in other habitats (i.e., urban areas, agriculture fields, and St. Lawrence
      River) were found in either sex. These findings suggest that animals breeding in
      the vicinity of WMFs as well as mobile species that only use these sites for
      short stopovers to forage, could be at risk of enhanced DecaBDE exposure. 

PMID- 25769126
TI  - The relationship between transportation noise exposure and ischemic heart
      disease: a meta-analysis.
AB  - BACKGROUND: There is a growing body of evidence that exposure to transportation
      related noise can adversely affect health and wellbeing. More recently, research
      on cardiovascular disease has specifically explored the hypothesis that exposure
      to transportation noise increases the risk for ischemic heart disease (IHD). Our
      objective was to review and conduct a meta-analysis to obtain an overall exposure
      response association. METHODS AND RESULTS: We conducted a systematic review and
      retained published studies on incident cases of IHD using sources of
      transportation noise as exposure. Study-specific results were transformed into
      risk estimates per 10dB increase in exposure. Subsequently we conducted a random
      effects meta-analysis to pool the estimates. We identified 10 studies on road and
      aircraft noise exposure conducted since the mid-1990s, providing a total of 12
      risk estimates. Pooled relative risk for IHD was 1.06 (1.03-1.09) per 10dB
      increase in noise exposure with the linear exposure-response starting at 50dB.
      Based on a small number of studies, subgroup analyses were suggestive of higher
      risk for IHD for males compared to females (p=0.14), and for persons over 65
      years of age compared to under (p=0.22). Air pollution adjustment, explored only
      in a subset of four studies, did not substantially attenuate the association
      between noise exposure and IHD. CONCLUSIONS: The evidence for an effect of
      transportation noise with IHD necessitates further research into the threshold
      and the shape of the exposure-response association, potential sources of
      heterogeneity and effect modification. Research in different cultural contexts is
      also important to derive regional and local estimates for the contribution of
      transportation noise to the global burden of disease.

PMID- 25769127
TI  - Air pollution and cytokine responsiveness in asthmatic and non-asthmatic
      children.
AB  - Epidemiological studies indicate that asthmatic children are more susceptible to
      traffic-related air pollution exposure than non-asthmatic children. Local and
      systemic inflammation in combination with oxidative stress have been suggested as
      a possible susceptibility factor. We investigated effect modification by asthma
      status for the association between air pollution exposure and systemic effects
      using whole blood cytokine responsiveness as an inflammatory marker. The study
      was nested within the two German birth cohort studies GINIplus and LISAplus and
      initially designed as a random sub-sample enriched with asthmatic children. Using
      data from 27 asthmatic and 59 non-asthmatic six-year-old children we measured the
      production of Interleukin-6 (IL)-6, IL-8, IL-10, monocyte chemotactic protein-1
      (MCP-1), tumour necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN
      gamma) in whole blood after ex-vivo stimulation with urban particulate matter
      (EHC-93). Air pollution exposure (nitrogen dioxide (NO2), nitrogen oxides (NOx),
      particulate matter with an aerodynamic diameter <10MUm (PM10), particulate matter
      with an aerodynamic diameter <2.5MUm (PM2.5mass), coarse particulate matter
      (PMcoarse) and PM2.5absorbance (PM2.5abs)) was modelled for children's home
      addresses applying land-use regression. To assess effect modification by asthma
      status linear regression models with multiplicative interaction terms were used.
      In asthmatics exposure to NO2 was associated with higher production of pro
      inflammatory cytokines: adjusted means ratio (MR) 2.22 (95% confidence interval
      1.22-4.04) for IL-6 per 2.68ug/m3 NO2. The interaction term between asthma status
      and NO2 exposure was significant. Results for NOx, PM10, PM2.5mass and PM2.5abs
      were in the same direction. No association between air pollution and cytokine
      responsiveness was found in the group of non-asthmatic children and in the
      overall group. Traffic-related air pollution exposure is associated with higher
      pro-inflammatory cytokine responsiveness in whole blood of asthmatic children. 

PMID- 25769128
TI  - CH4 and N2O emissions from China's beef feedlots with ad libitum and restricted
      feeding in fall and spring seasons.
AB  - Accurately quantifying methane (CH4) and nitrous oxide (N2O) emissions from beef
      operations in China is necessary to evaluate the contribution of beef cattle to
      greenhouse gas budgets at the national and global level. Methane and N2O
      emissions from two intensive beef feedlots in the North China Plain, one with a
      restricted feeding strategy and high manure collection frequency and the other
      with an ad libitum feeding strategy and low manure collection frequency, were
      quantified in the fall and spring seasons using an inverse dispersion technique.
      The diel pattern of CH4 from the beef feedlot with an ad libitum feed strategy
      (single peak during a day) differed from that under a restricted feeding
      condition (multiple peaks during a day), but little difference in the diel
      pattern of N2O emissions between two feeding strategies was observed. The two
      season average CH4 emission rates of the two intensive feedlots were 230 and
      198gCH4animal(-1)d(-1) and accounted for 6.7% and 6.8% of the gross energy
      intake, respectively, indicating little impact of the feeding strategy and manure
      collection frequency on the CH4 conversion factor at the feedlot level. However,
      the average N2O emission rates (21.2g N2Oanimal(-1)d(-1)) and conversion factor
      (8.5%) of the feedlot with low manure collection frequency were approximately
      131% and 174% greater, respectively, than the feedlot under high frequency
      conditions, which had a N2O emission rate and conversion factor of 9.2g
      N2Oanimal(-1)d(-1) and 3.1%, respectively, indicating that increasing manure
      collection frequency played an important role in reducing N2O emissions from beef
      feedlots. In addition, comparison indicated that China's beef and dairy cattle in
      feedlots appeared to have similar CH4 conversion factors. 

PMID- 25769129
TI  - Recycling process for recovery of gallium from GaN an e-waste of LED industry
      through ball milling, annealing and leaching.
AB  - Waste dust generated during manufacturing of LED contains significant amounts of
      gallium and indium, needs suitable treatment and can be an important resource for
      recovery. The LED industry waste dust contains primarily gallium as GaN. Leaching
      followed by purification technology is the green and clean technology. To develop
      treatment and recycling technology of these GaN bearing e-waste, leaching is the
      primary stage. In our current investigation possible process for treatment and
      quantitative leaching of gallium and indium from the GaN bearing e-waste or waste
      of LED industry dust has been developed. To recycle the waste and quantitative
      leaching of gallium, two different process flow sheets have been proposed. In
      one, process first the GaN of the waste the LED industry dust was leached at the
      optimum condition. Subsequently, the leach residue was mixed with Na2CO3, ball
      milled followed by annealing, again leached to recover gallium. In the second
      process, the waste LED industry dust was mixed with Na2CO3, after ball milling
      and annealing, followed acidic leaching. Without pretreatment, the gallium
      leaching was only 4.91 w/w % using 4M HCl, 100 degrees C and pulp density of
      20g/L. After mechano-chemical processing, both these processes achieved 73.68 w/w
      % of gallium leaching at their optimum condition. The developed process can treat
      and recycle any e-waste containing GaN through ball milling, annealing and
      leaching. 

PMID- 25769130
TI  - Comparison of practical techniques to develop latent fingermarks on fired and
      unfired cartridge cases.
AB  - We have tested some widely used and practical fingermark enhancement techniques
      such as powdering (regular powder dusting and magnetic powder application),
      cyanoacrylate fuming, fluorescent dying (basic yellow 40), gun blueing solutions
      and acidified hydrogen peroxide solutions. The results were evaluated and
      compared in order to establish best procedures on processing cartridge cases. The
      tests were performed on brass discs subjected to three different temperatures
      (room temperature, 63 and 200 degrees C), and on fired and unfired cartridge
      cases. All the samples were processed after three different periods of time (24h,
      7 days and 14 days) after deposition. The best results for both fired and unfired
      cartridge cases were obtained by the sequential application of cyanoacrylate, gun
      blueing solution and basic yellow 40. Some stages of the firing process were
      isolated in order to identify their effects over the final amount and quality of
      the remaining latent fingermarks on cartridge cases. Good state fingermarks were
      developed on unfired cartridge cases cycled through the gun, showing that
      friction inside the gun without firing does not cause significant damage to the
      fingermarks. On the other hand, fired cartridge cases are significantly affected
      by the firing effects, exhibiting low quality ridge details which are mainly
      located next to base. An unexpected phenomenon was observed on most of the brass
      discs heated to 200 degrees C and developed with gun blueing solutions; they
      presented a reverse development compared to the expected one, with darkening of
      the ridges instead of the background. 

PMID- 25769131
TI  - The importance of microbiological testing for establishing cause of death in 42
      forensic autopsies.
AB  - Microorganisms have always been one of the great challenges of humankind, being
      responsible for both high morbidity and mortality throughout history. In a
      forensic setting microbiological information will always be difficult to
      interpret due to lack of antemortem information and changes in flora postmortem.
      With this study we aim to review the use of microbiological procedures at our
      forensic institute. In a retrospective study including 42 autopsies performed at
      our Institute, where microbiological test had been applied, analyses were made
      with regard to: type of microbiological tests performed, microorganisms found,
      histological findings, antemortem information, C-reactive protein measurement and
      cause of death. Fiftyone different microorganisms were found distributed among 37
      cases, bacteria being the most abundant. Nineteen of the cases were classified as
      having a microbiological related cause of death. C-reactive protein levels were
      raised in 14 cases of the 19 cases, histological findings either supported or
      were a decisive factor for the classification of microbiologically related cause
      of death in 14 cases. As a multitude of abundant microorganisms are able to cause
      infection under the right circumstances, all findings should be compared to
      anamnestic antemortem information, before conclusions are drawn. A definite list
      of true pathogens is nearly impossible to compile. 

PMID- 25769132
TI  - Pharmacokinetics of reduced iso-alpha-acids in volunteers following clear bottled
      beer consumption.
AB  - Reduced iso-alpha-acids (reduced IAA) consisting of the rho-, tetrahydro- and
      hexahydro-IAA groups (RIAA, TIAA and HIAA, respectively) are ingredient congeners
      specific to beer and generally found in clear and also occasionally green bottled
      beer. Concentrations of reduced IAA were determined in the blood and urine of
      five volunteers over 6h following the consumption of small volumes of beer
      containing each of the reduced IAA. The reduced IAA were absorbed and
      bioavailable with peak concentrations at 0.5h followed by a drop of generally
      fivefold by 2h. Preliminary pharmacokinetics of these compounds in humans shows
      relatively small inter-individual differences and an estimated short half-life
      varying between ~38 and 46min for the three groups. Comparison of RIAA analyte
      ratios within the group indicate that some analytes eliminate relatively faster
      than others and the formation of metabolite products was observed. Preliminary
      urine analysis showed only unmodified RIAA analytes were detectable throughout 6h
      and suggests extensive phase I metabolism of TIAA and HIAA analytes. In authentic
      forensic casework where clear or green bottled beers are consumed, the
      identification of reduced IAA groups may provide a novel method to target
      ingredient congeners consistent with beer ingestion and suggest the type of beer
      consumed. 

PMID- 25769134
TI  - Morphological parameters for implantation of the screwless spring loop dynamic
      posterior spinous process stabilizing system.
AB  - PURPOSE: This study aimed to quantify morphological characteristics of the
      posterior lumbar spinous process, which may affect stable implantation of
      screwless wire spring loops. METHODS: Virtual implantations of a screwless wire
      spring loop onto pairs of lumbar spinous processes were performed for computed
      tomography (CT)-derived three-dimensional vertebral models of 40 Korean subjects.
      Morphological parameters of lumbar vertebrae 1 through 5 (L1-L5) were measured
      with regard to bone-implant interference. RESULTS: In males, the transspinous
      process fixation lengths decreased from 57.8+/-3.0mm to 48.8+/-3.2mm as the
      lumbar joints descend from L1-L2 to L4-L5, with those in females about 4.1+/
      0.4mm shorter (p<0.05) than in males through all lumbar joints. The fixation
      angle on the sagittal plane varied from 105.0 degrees  to 101.3 degrees  relative
      to the transverse plane as the vertebrae descend. The clenched thickness in
      females was the least (6.7+/-1.2mm) for the L2 lower spinous process and the
      greatest (8.1+/-2.2mm) for the L4 upper spinous process; this was 1.0+/-10.3mm
      less than that for males at corresponding levels (p>0.05). The ratio of the
      spinous process clenched thickness to the transspinous fixation length increased
      from 0.133+/-0.016 to 0.196+/-0.076 for the upper spinous processes as the lumbar
      joints descend. CONCLUSIONS: The ratio of the spinous process clenched thickness
      to the transspinous fixation length varies, depending on gender and whether the
      clenched level is the upper or lower spinous process. These parameters related to
      the clenching fixation stability should be considered in development and
      implantations of the screwless wire spring loop.

PMID- 25769133
TI  - Response inhibition and response monitoring in a saccadic double-step task in
      schizophrenia.
AB  - BACKGROUND: Cognitive control impairments are linked to functional outcome in
      schizophrenia. The goal of the current study was to investigate precise
      abnormalities in two aspects of cognitive control: reactively changing a prepared
      response, and monitoring performance and adjusting behavior accordingly. We
      adapted an oculomotor task from neurophysiological studies of the cellular basis
      of cognitive control in nonhuman primates. METHODS: 16 medicated outpatients with
      schizophrenia (SZ) and 18 demographically-matched healthy controls performed the
      modified double-step task. In this task, participants were required to make a
      saccade to a visual target. Infrequently, the target jumped to a new location and
      participants were instructed to rapidly inhibit and change their response. A race
      model provided an estimate of the time needed to cancel a planned movement.
      Response monitoring was assessed by measuring reaction time (RT) adjustments
      based on trial history. RESULTS: SZ patients had normal visually-guided saccadic
      RTs but required more time to switch the response to the new target location.
      Additionally, the estimated latency of inhibition was longer in patients and
      related to employment. Finally, although both groups slowed down on trials that
      required inhibiting and changing a response, patients showed exaggerated
      performance-based adjustments in RTs, which was correlated with positive symptom
      severity. CONCLUSIONS: SZ patients have impairments in rapidly inhibiting eye
      movements and show idiosyncratic response monitoring. These results are
      consistent with functional abnormalities in a network involving cortical
      oculomotor regions, the superior colliculus, and basal ganglia, as described in
      neurophysiological studies of non-human primates using an identical paradigm, and
      provide a translational bridge for understanding cognitive symptoms of SZ.

PMID- 25769136
TI  - Molluscicide baits impair the life traits of Folsomia candida (Collembola):
      Possible hazard to the population level and soil function.
AB  - The application of molluscicides baits on the soil surface is the most common
      practice to control terrestrial gastropods. There seems to be a gap in the
      accurate evaluation of molluscicidal baits effects to soil arthropods, since
      their hazard to non-target organisms has been considered low after mixing baits
      into soil. In this work the ecotoxicological effects of two molluscicide baits
      (metaldehyde and methiocarb) to the collembolan Folsomia candida were evaluated
      using two different approaches: (1) molluscicidal baits were applied to the top
      soil once and only at the beginning of the exposure and avoidance behaviour and
      reproduction were evaluated; and (2) baits were replaced by new ones after 14-d
      of exposure, simulating the recommended application rate recommended by the
      manufacturer and reproduction was assessed (repeated/pulse exposure). A
      preference for the side contaminated for methiocarb was observed but the
      distribution of collembolans in the avoidance test with metaldehyde was random.
      Exposure to metaldehyde resulted in a significant increase in mortality. For
      methiocarb, a reduction in the juveniles produced but no acute effects were
      observed. In the bait pulse test, the toxic effects of each chemical was
      significantly increased compared with the single exposure test, for all
      treatments used (both reproduction and mortality). In summary, molluscicides have
      an adverse effect on F. candida, with severe effects on their behaviour (only for
      methiocarb), reproduction and survival (for both), which can lead to population
      collapse with time. 

PMID- 25769135
TI  - Morphometric analysis of somatotropic cells of the adenohypophysis and muscle
      fibers of the psoas muscle in the process of aging in humans.
AB  - The aim of this research was to quantify changes of the adenohypophyseal
      somatotropes and types 1 and 2 muscle fibers with aging, as well as to establish
      mutual interactions and correlations with age. Material was samples of hypophysis
      and psoas major muscle of 27 cadavers of both genders, aged from 30 to 90 years.
      Adenohypophyseal and psoas major tissue sections were immunohistochemically
      processed and stained by anti-human growth hormone and anti-fast myosin
      antibodies, respectively. Morphometric analysis was performed by ImageJ. Results
      of morphometric analysis showed a significant increase in the somatotrope area,
      and significant decrease in somatotrope volume density and nucleocytoplasmic
      ratio with age. Cross-sectional areas of types 1 and 2, and volume density of
      type 2 muscle fibers decreased significantly with age. One Way ANOVA showed that
      the latter cited changes in the somatotropes and types 1 and 2 muscle fibers
      mostly become significant after the age of 70. Significant positive correlation
      was observed between the area of the somatotropes and volume density of type 2
      muscle fibers. A significant negative correlation was detected between the
      nucleocytoplasmic ratio of the somatotropes and cross-sectional areas of types 1
      and 2 muscle fibers. So, it can be concluded that after the age of 70, there is
      significant loss of the anterior pituitary's somatotropes associated with
      hypertrophy and possible functional decline of the remained cells. Age-related
      changes in the somatotropes are correlated with the simultaneous atrophy of type
      1, as well as with the atrophy and loss of type 2 muscle fibers.

PMID- 25769137
TI  - Differences in volatile profiles of Cabernet Sauvignon grapes grown in two
      distinct regions of China and their responses to weather conditions.
AB  - Volatile compounds are considered important for plants to communicate with each
      other and interact with their environments. Most wine-producing regions in China
      feature a continental monsoon climate with hot-wet summers and dry-cold winters,
      giving grapes markedly different growing environments compared to the
      Mediterranean or oceanic climates described in previous reports. This study
      focused on comparing the volatile profiles of Vitis vinifera L. cv. Cabernet
      Sauvignon berries from two regions with distinct climate characteristics: Changli
      has a warm and semi-humid summer, and Gaotai has a cool-arid summer and a cold
      winter. The relationship between meteorological metrics and the concentrations of
      grape volatiles were also examined. In harvested grapes, benzyl alcohol,
      phenylethyl alcohol, 1-hexanol and 1-octen-3-ol were more abundant in the Changli
      berries, while hexanal, heptanal, 2-methoxy-3-isobutylpyrazine, and (E)-beta
      damascenone presented higher levels in the Gaotai berries. The fluctuation in the
      accumulation of volatile compounds observed during berry development was closely
      correlated with variations in short-term weather (weather in a week), especially
      rainfall. The concentration of some volatiles, notably aliphatic aldehydes, was
      significantly related to diurnal temperature differences. The variability during
      berry development of concentrations for compounds such as C6 volatile compounds,
      2-methoxy-3-isobutylpyrazine and (E)-beta-damascenone strongly depended upon
      weather conditions. This work expands our knowledge about the influence of
      continental monsoon climates on volatile compounds in developing grape berries.
      It will also improve the comprehension of the plant response to their surrounding
      environments through the accumulation of volatiles. The results will help growers
      to alter viticultural practices according to local conditions to improve the
      aromatic quality of grapes. 

PMID- 25769139
TI  - Color correction using root-polynomial regression.
AB  - Cameras record three color responses (RGB) which are device dependent. Camera
      coordinates are mapped to a standard color space, such as XYZ-useful for color
      measurement-by a mapping function, e.g., the simple 3*3 linear transform (usually
      derived through regression). This mapping, which we will refer to as linear color
      correction (LCC), has been demonstrated to work well in the number of studies.
      However, it can map [Formula: see text] to XYZs with high error. The advantage of
      the LCC is that it is independent of camera exposure. An alternative and
      potentially more powerful method for color correction is polynomial color
      correction (PCC). Here, the R, G, and B values at a pixel are extended by the
      polynomial terms. For a given calibration training set PCC can significantly
      reduce the colorimetric error. However, the PCC fit depends on exposure, i.e., as
      exposure changes the vector of polynomial components is altered in a nonlinear
      way which results in hue and saturation shifts. This paper proposes a new
      polynomial-type regression loosely related to the idea of fractional polynomials
      which we call root-PCC (RPCC). Our idea is to take each term in a polynomial
      expansion and take its k th root of each k -degree term. It is easy to show terms
      defined in this way scale with exposure. RPCC is a simple (low complexity)
      extension of LCC. The experiments presented in this paper demonstrate that RPCC
      enhances color correction performance on real and synthetic data.

PMID- 25769140
TI  - Depth superresolution by transduction.
AB  - This paper presents a depth superresolution (SR) method that uses both of a low
      resolution (LR) depth image and a high-resolution (HR) intensity image. We
      formulate depth SR as a graph-based transduction problem. In particular, the HR
      intensity image is represented as an undirected graph, in which pixels are
      characterized as vertices, and their relations are encoded as an affinity
      function. When the vertices initially labeled with certain depth hypotheses (from
      the LR depth image) are regarded as input queries, all the vertices are scored
      with respect to the relevances to these queries by a classifying function. Each
      vertex is then labeled with the depth hypothesis that receives the highest
      relevance score. We design the classifying function by considering the local and
      global structures of the HR intensity image. This approach enables us to address
      a depth bleeding problem that typically appears in current depth SR methods.
      Furthermore, input queries are assigned in a probabilistic manner, making depth
      SR robust to noisy depth measurements. We also analyze existing depth SR methods
      in the context of transduction, and discuss their theoretic relations. Intensive
      experiments demonstrate the superiority of the proposed method over state-of-the
      art methods both qualitatively and quantitatively. 

PMID- 25769138
TI  - Cephalometric study to test the reliability of anteroposterior skeletal
      discrepancy indicators using the twin block appliance.
AB  - BACKGROUND: The objectives of this study were to check the reliability of the
      five angular and two linear parameters for sagittal maxillo-mandibular
      discrepancy and to compare and correlate angular parameters with the ANB angle,
      and the linear parameter with Wits analysis. METHODS: The pre-treatment and post
      functional lateral cephalograms of 25 subjects (17 males, 8 females) with class
      II division 1 malocclusion treated with twin block functional appliance were
      selected. Five angular (ANB, beta angle, APDI, YEN angle, W angle) and two linear
      (Wits analysis, App-Bpp) parameters were traced on both sets of cephalograms.
      Paired Student's t-test, one-way ANOVA, post hoc test, and Karl Pearson
      correlation statistical analysis were performed. RESULTS: All the parameters
      considered in our study showed highly significant difference in pre-treatment and
      post-functional values, suggesting their reliability (p < 0.0001). When ANB angle
      was compared with the other angular parameters, a highly significant change in
      the mean value of the difference in pre-treatment (T1) and post-functional (T2)
      values was noted (p < 0.001). No significant change was seen when comparing the
      mean value of the difference in T1 and T2 between linear parameters (p = 0.949).
      CONCLUSIONS: All the parameters used in the study can be reliably used to assess
      anteroposterior skeletal discrepancy. Whenever limitations of the ANB angle and
      Wits analysis are foreseen, the W angle and App-Bpp, respectively, can be
      reliably used. The YEN angle may reliably predict the post-functional change with
      the use of twin block appliance.

PMID- 25769141
TI  - EEG-Based Tonic Cold Pain Characterization Using Wavelet Higher Order Spectral
      Features.
AB  - A novel approach in tonic cold pain characterization, based on
      electroencephalograph (EEG) data analysis using wavelet higher order spectral
      (WHOS) features, is presented here. The proposed WHOS-based feature space extends
      the relative power spectrum-based (phase blind) approaches reported so far a step
      forward; this is realized via dynamic monitoring of the nonlinerities of the EEG
      brain response to tonic cold pain stimuli by capturing the change in the
      underlying quadratic phase coupling at the bifrequency wavelet
      bispectrum/bicoherence domain due to the change of the pain level. Three pain
      characterization scenarios were formed and experimentally tested involving WHOS
      based analysis of EEG data, acquired from 17 healthy volunteers that were
      subjected to trials of tonic cold pain stimuli. The experimental and
      classification analysis results, based on four well-known classifiers, have shown
      that the WHOS-based features successfully discriminate relax from pain status,
      provide efficient identification of the transition from relax to mild and/or
      severe pain status, and translate the subjective perception of pain to an
      objective measure of pain endurance. These findings seem quite promising and pave
      the way for adopting WHOS-based approaches to pain characterization under other
      types of pain, e.g., chronic pain and various clinical scenarios. 

PMID- 25769142
TI  - Using Kalman Filtering to Predict Time-Varying Parameters in a Model Predicting
      Baroreflex Regulation During Head-Up Tilt.
AB  - The cardiovascular control system is continuously engaged to maintain
      homeostasis, but it is known to fail in a large cohort of patients suffering from
      orthostatic intolerance. Numerous clinical studies have been put forward to
      understand how the system fails, yet noninvasive clinical data are sparse,
      typical studies only include measurements of heart rate and blood pressure, as a
      result it is difficult to determine what mechanisms that are impaired. It is
      known, that blood pressure regulation is mediated by changes in heart rate,
      vascular resistance, cardiac contractility, and a number of other factors. Given
      that numerous factors contribute to changing these quantities, it is difficult to
      devise a physiological model describing how they change in time. One way is to
      build a model that allows these controlled quantities to change and to compare
      dynamics between subject groups. To do so, it requires more knowledge of how
      these quantities change for healthy subjects. This study compares two methods
      predicting time-varying changes in cardiac contractility and vascular resistance
      during head-up tilt. Similar to the study by Williams et al. [51], the first
      method uses piecewise linear splines, while the second uses the ensemble
      transform Kalman filter (ETKF) [1], [11], [12], [33]. In addition, we show that
      the delayed rejection adaptive Metropolis (DRAM) algorithm can be used for
      predicting parameter uncertainties within the spline methodology, which is
      compared with the variability obtained with the ETKF. While the spline method is
      easier to set up, this study shows that the ETKF has a significantly shorter
      computational time. Moreover, while uncertainty of predictions can be augmented
      to spline predictions using DRAM, these are readily available with the ETKF.

PMID- 25769143
TI  - Segmentation, Separation and Pose Estimation of Prostate Brachytherapy Seeds in
      CT Images.
AB  - GOAL: In this paper, we address the development of an automatic approach for the
      computation of pose information (position + orientation) of prostate
      brachytherapy loose seeds from 3-D CT images. METHODS: From an initial detection
      of a set of seed candidates in CT images using a threshold and connected
      component method, the orientation of each individual seed is estimated by using
      the principal components analysis method. The main originality of this approach
      is the ability to classify the detected objects based on a priori intensity and
      volume information and to separate groups of closely spaced seeds using three
      competing clustering methods: the standard and a modified k-means method and a
      Gaussian mixture model with an expectation-maximization algorithm. Experiments
      were carried out on a series of CT images of two phantoms and patients. The
      fourteen patients correspond to a total of 1063 implanted seeds. Detections are
      compared to manual segmentation and to related work in terms of detection
      performance and calculation time. RESULTS: This automatic method has proved to be
      accurate and fast including the ability to separate groups of seeds in a reliable
      way and to determine the orientation of each seed. SIGNIFICANCE: Such a method is
      mandatory to be able to compute precisely the real dose delivered to the patient
      postoperatively instead of assuming the alignment of seeds along the theoretical
      insertion direction of the brachytherapy needles.

PMID- 25769144
TI  - Acoustic Gaits: Gait Analysis With Footstep Sounds.
AB  - We describe the acoustic gaits-the natural human gait quantitative
      characteristics derived from the sound of footsteps as the person walks normally.
      We introduce the acoustic gait profile, which is obtained from temporal signal
      analysis of sound of footsteps collected by microphones and illustrate some of
      the spatio-temporal gait parameters that can be extracted from the acoustic gait
      profile by using three temporal signal analysis methods-the squared energy
      estimate, Hilbert transform and Teager-Kaiser energy operator. Based on the
      statistical analysis of the parameter estimates, we show that the spatio-temporal
      parameters and gait characteristics obtained using the acoustic gait profile can
      consistently and reliably estimate a subset of clinical and biometric gait
      parameters currently in use for standardized gait assessments. We conclude that
      the Teager-Kaiser energy operator provides the most consistent gait parameter
      estimates showing the least variation across different sessions and zones.
      Acoustic gaits use an inexpensive set of microphones with a computing device as
      an accurate and unintrusive gait analysis system. This is in contrast to the
      expensive and intrusive systems currently used in laboratory gait analysis such
      as the force plates, pressure mats and wearable sensors, some of which may change
      the gait parameters that are being measured. 

PMID- 25769145
TI  - Seismocardiography-Based Detection of Cardiac Quiescence.
AB  - Cardiac-computed tomography angiography (CTA) is a minimally invasive imaging
      technology for characterizing coronary arteries. A fundamental limitation of CTA
      imaging is cardiac movement, which can cause artifacts and reduce the quality of
      the obtained images. To mitigate this problem, current approaches involve gating
      the image based on the electrocardiogram (ECG) to predict the timing of quiescent
      periods of the cardiac cycle. This paper focuses on developing a foundation for
      using a mechanical alternative to the ECG for finding these quiescent periods:
      the seismocardiogram (SCG). SCG was used to determine beat-by-beat systolic and
      diastolic quiescent periods of the cardiac cycle for nine healthy subjects, and
      11 subjects with various cardiovascular diseases. To reduce noise in the SCG, and
      quantify these quiescent periods, a Kalman filter was designed to extract the
      velocity of chest wall movement from the recorded SCG signals. The average
      systolic and diastolic quiescent periods were centered at 29% and 76% for the
      healthy subjects, and 33% and 79% for subjects with cardiovascular disease. Both
      inter and intrasubject variability in the quiescent phases were observed compared
      to ECG-predicted phases, suggesting that the ECG may be a suboptimal modality for
      predicting quiescence, and that the SCG provides complementary data to the ECG. 

PMID- 25769146
TI  - Stratified Sampling Voxel Classification for Segmentation of Intraretinal and
      Subretinal Fluid in Longitudinal Clinical OCT Data.
AB  - Automated three-dimensional retinal fluid (named symptomatic exudate-associated
      derangements, SEAD) segmentation in 3D OCT volumes is of high interest in the
      improved management of neovascular Age Related Macular Degeneration (AMD). SEAD
      segmentation plays an important role in the treatment of neovascular AMD, but
      accurate segmentation is challenging because of the large diversity of SEAD size,
      location, and shape. Here a novel voxel classification based approach using a
      layer-dependent stratified sampling strategy was developed to address the class
      imbalance problem in SEAD detection. The method was validated on a set of 30
      longitudinal 3D OCT scans from 10 patients who underwent anti-VEGF treatment. Two
      retinal specialists manually delineated all intraretinal and subretinal fluid.
      Leave-one-patient-out evaluation resulted in a true positive rate and true
      negative rate of 96% and 0.16% respectively. This method showed promise for image
      guided therapy of neovascular AMD treatment.

PMID- 25769147
TI  - Automated Vessel Segmentation Using Infinite Perimeter Active Contour Model with
      Hybrid Region Information with Application to Retinal Images.
AB  - Automated detection of blood vessel structures is becoming of crucial interest
      for better management of vascular disease. In this paper, we propose a new
      infinite active contour model that uses hybrid region information of the image to
      approach this problem. More specifically, an infinite perimeter regularizer,
      provided by using L(2) Lebesgue measure of the gamma -neighborhood of boundaries,
      allows for better detection of small oscillatory (branching) structures than the
      traditional models based on the length of a feature's boundaries (i.e., H(1)
      Hausdorff measure). Moreover, for better general segmentation performance, the
      proposed model takes the advantage of using different types of region
      information, such as the combination of intensity information and local phase
      based enhancement map. The local phase based enhancement map is used for its
      superiority in preserving vessel edges while the given image intensity
      information will guarantee a correct feature's segmentation. We evaluate the
      performance of the proposed model by applying it to three public retinal image
      datasets (two datasets of color fundus photography and one fluorescein
      angiography dataset). The proposed model outperforms its competitors when
      compared with other widely used unsupervised and supervised methods. For example,
      the sensitivity (0.742), specificity (0.982) and accuracy (0.954) achieved on the
      DRIVE dataset are very close to those of the second observer's annotations. 

PMID- 25769148
TI  - Joint Estimation of Activity and Attenuation in Whole-Body TOF PET/MRI Using
      Constrained Gaussian Mixture Models.
AB  - It has recently been shown that the attenuation map can be estimated from time-of
      flight (TOF) PET emission data using joint maximum likelihood reconstruction of
      attenuation and activity (MLAA). In this work, we propose a novel MRI-guided MLAA
      algorithm for emission-based attenuation correction in whole-body PET/MR imaging.
      The algorithm imposes MR spatial and CT statistical constraints on the MLAA
      estimation of attenuation maps using a constrained Gaussian mixture model (GMM)
      and a Markov random field smoothness prior. Dixon water and fat MR images were
      segmented into outside air, lung, fat and soft-tissue classes and an MR low
      intensity (unknown) class corresponding to air cavities, cortical bone and
      susceptibility artifacts. The attenuation coefficients over the unknown class
      were estimated using a mixture of four Gaussians, and those over the known tissue
      classes using unimodal Gaussians, parameterized over a patient population. To
      eliminate misclassification of spongy bones with surrounding tissues, and thus
      include them in the unknown class, we heuristically suppressed fat in water
      images and also used a co-registered bone probability map. The proposed MLAA-GMM
      algorithm was compared with the MLAA algorithms proposed by Rezaei and Salomon
      using simulation and clinical studies with two different tracer distributions.
      The results showed that our proposed algorithm outperforms its counterparts in
      suppressing the cross-talk and scaling problems of activity and attenuation and
      thus produces PET images of improved quantitative accuracy. It can be concluded
      that the proposed algorithm effectively exploits the MR information and can pave
      the way toward accurate emission-based attenuation correction in TOF PET/MRI. 

PMID- 25769149
TI  - Feature-Preserving Noise Removal.
AB  - Conventional image restoration algorithms use transform-domain filters, which
      separate the noise from the sparse signal among the transform components or apply
      spatial smoothing filters in real space whose design relies on prior assumptions
      about the noise statistics. These filters also reduce the information content of
      the image by suppressing spatial frequencies or by recognizing only a limited set
      of shapes. Here we show that denoising can be efficiently done using a nonlinear
      filter, which operates along patch neighborhoods and multiple copies of the
      original image. The use of patches enables the algorithm to account for spatial
      correlations in the random field whereas the multiple copies are used to
      recognize the noise statistics. The nonlinear filter, which is implemented by a
      hierarchical multistage system of multilayer perceptrons, outperforms state-of
      the-art denoising algorithms such as those based on collaborative filtering and
      total variation. Compared to conventional denoising algorithms, our filter can
      restore images without blurring them, making it attractive for use in medical
      imaging where the preservation of anatomical details is critical. 

PMID- 25769150
TI  - Evaluation of Fisher Information Matrix-Based Methods for Fast Assessment of
      Image Quality in Pinhole SPECT.
AB  - The accurate determination of the local impulse response and the covariance in
      voxels from penalized maximum likelihood reconstructed images requires performing
      reconstructions from many noise realizations of the projection data. As this is
      usually a very time-consuming process, efficient analytical approximations based
      on the Fisher information matrix (FIM) have been extensively used in PET and
      SPECT to estimate these quantities. For 3D imaging, however, additional
      approximations need to be made to the FIM in order to speed up the calculations.
      The most common approach is to use the local shift-invariant (LSI) approximation
      of the FIM, but this assumes specific conditions which are not always necessarily
      valid. In this paper we take a single-pinhole SPECT system and compare the
      accuracy of the LSI approximation against two other methods that have been more
      recently put forward: the non-uniform object-space pixelation (NUOP) and the
      subsampled FIM. These methods do not assume such restrictive conditions while
      still increasing the speed of the calculations considerably. Our results indicate
      that in pinhole SPECT the NUOP and subsampled FIM approaches could be more
      reliable than the LSI approximation, especially when a high accuracy is required.

PMID- 25769151
TI  - Depth reconstruction from sparse samples: representation, algorithm, and
      sampling.
AB  - The rapid development of 3D technology and computer vision applications has
      motivated a thrust of methodologies for depth acquisition and estimation.
      However, existing hardware and software acquisition methods have limited
      performance due to poor depth precision, low resolution, and high computational
      cost. In this paper, we present a computationally efficient method to estimate
      dense depth maps from sparse measurements. There are three main contributions.
      First, we provide empirical evidence that depth maps can be encoded much more
      sparsely than natural images using common dictionaries, such as wavelets and
      contourlets. We also show that a combined wavelet-contourlet dictionary achieves
      better performance than using either dictionary alone. Second, we propose an
      alternating direction method of multipliers (ADMM) for depth map reconstruction.
      A multiscale warm start procedure is proposed to speed up the convergence. Third,
      we propose a two-stage randomized sampling scheme to optimally choose the
      sampling locations, thus maximizing the reconstruction performance for a given
      sampling budget. Experimental results show that the proposed method produces high
      quality dense depth estimates, and is robust to noisy measurements. Applications
      to real data in stereo matching are demonstrated. 

PMID- 25769152
TI  - Max-confidence boosting with uncertainty for visual tracking.
AB  - The challenges in visual tracking call for a method which can reliably recognize
      the subject of interests in an environment, where the appearance of both the
      background and the foreground change with time. Many existing studies model this
      problem as tracking by classification with online updating of the classification
      models, however, most of them overlook the ambiguity in visual modeling and do
      not consider the prior information in the tracking process. In this paper, we
      present a novel visual tracking method called max-confidence boosting (MCB),
      which explores a new way of online updating ambiguous visual phenomenon. The MCB
      framework models uncertainty in prior knowledge utilizing the indeterministic
      labels, which are used in updating models from previous frames and the new frame.
      Our proposed MCB tracker allows ambiguity in the tracking process and can
      effectively alleviate the drift problem. Many experimental results in challenging
      video sequences verify the success of our method, and our MCB tracker outperforms
      a number of the state-of-the-art tracking by classification methods.

PMID- 25769153
TI  - A chi-squared-transformed subspace of LBP histogram for visual recognition.
AB  - Local binary pattern (LBP) and its variants have been widely used in many
      recognition tasks. Subspace approaches are often applied to the LBP feature in
      order to remove unreliable dimensions, or to derive a compact feature
      representation. It is well-known that subspace approaches utilizing up to the
      second-order statistics are optimal only when the underlying distribution is
      Gaussian. However, due to its nonnegative and simplex constraints, the LBP
      feature deviates significantly from Gaussian distribution. To alleviate this
      problem, we propose a chi-squared transformation (CST) to transfer the LBP
      feature to a feature that fits better to Gaussian distribution. The proposed CST
      leads to the formulation of a two-class classification problem. Due to its
      asymmetric nature, we apply asymmetric principal component analysis (APCA) to
      better remove the unreliable dimensions in the CST feature space. The proposed
      CST-APCA is evaluated extensively on spatial LBP for face recognition, protein
      cellular classification, and spatial-temporal LBP for dynamic texture
      recognition. All experiments show that the proposed feature transformation
      significantly enhances the recognition accuracy. 

PMID- 25769154
TI  - Swarm intelligence for detecting interesting events in crowded environments.
AB  - This paper focuses on detecting and localizing anomalous events in videos of
      crowded scenes, i.e., divergences from a dominant pattern. Both motion and
      appearance information are considered, so as to robustly distinguish different
      kinds of anomalies, for a wide range of scenarios. A newly introduced concept
      based on swarm theory, histograms of oriented swarms (HOS), is applied to capture
      the dynamics of crowded environments. HOS, together with the well-known
      histograms of oriented gradients, are combined to build a descriptor that
      effectively characterizes each scene. These appearance and motion features are
      only extracted within spatiotemporal volumes of moving pixels to ensure
      robustness to local noise, increase accuracy in the detection of local,
      nondominant anomalies, and achieve a lower computational cost. Experiments on
      benchmark data sets containing various situations with human crowds, as well as
      on traffic data, led to results that surpassed the current state of the art
      (SoA), confirming the method's efficacy and generality. Finally, the experiments
      show that our approach achieves significantly higher accuracy, especially for
      pixel-level event detection compared to SoA methods, at a low computational cost.

PMID- 25769155
TI  - Adaptive regularization with the structure tensor.
AB  - Natural images exhibit geometric structures that are informative of the
      properties of the underlying scene. Modern image processing algorithms respect
      such characteristics by employing regularizers that capture the statistics of
      natural images. For instance, total variation (TV) respects the highly kurtotic
      distribution of the pointwise gradient by allowing for large magnitude outlayers.
      However, the gradient magnitude alone does not capture the directionality and
      scale of local structures in natural images. The structure tensor provides a more
      meaningful description of gradient information as it describes both the size and
      orientation of the image gradients in a neighborhood of each point. Based on this
      observation, we propose a variational model for image reconstruction that employs
      a regularization functional adapted to the local geometry of image by means of
      its structure tensor. Our method alternates two minimization steps: 1) robust
      estimation of the structure tensor as a semidefinite program and 2)
      reconstruction of the image with an adaptive regularizer defined from this
      tensor. This two-step procedure allows us to extend anisotropic diffusion into
      the convex setting and develop robust, efficient, and easy-to-code algorithms for
      image denoising, deblurring, and compressed sensing. Our method extends naturally
      to nonlocal regularization, where it exploits the local self-similarity of
      natural images to improve nonlocal TV and diffusion operators. Our experiments
      show a consistent accuracy improvement over classic regularization. 

PMID- 25769156
TI  - Learning person-person interaction in collective activity recognition.
AB  - Collective activity is a collection of atomic activities (individual person's
      activity) and can hardly be distinguished by an atomic activity in isolation. The
      interactions among people are important cues for recognizing collective activity.
      In this paper, we concentrate on modeling the person-person interactions for
      collective activity recognition. Rather than relying on hand-craft description of
      the person-person interaction, we propose a novel learning-based approach that is
      capable of computing the class-specific person-person interaction patterns. In
      particular, we model each class of collective activity by an interaction matrix,
      which is designed to measure the connection between any pair of atomic activities
      in a collective activity instance. We then formulate an interaction response (IR)
      model by assembling all these measurements and make the IR class specific and
      distinct from each other. A multitask IR is further proposed to jointly learn
      different person-person interaction patterns simultaneously in order to learn the
      relation between different person-person interactions and keep more distinct
      activity-specific factor for each interaction at the same time. Our model is able
      to exploit discriminative low-rank representation of person-person interaction.
      Experimental results on two challenging data sets demonstrate our proposed model
      is comparable with the state-of-the-art models and show that learning person
      person interactions plays a critical role in collective activity recognition. 

PMID- 25769157
TI  - Surface reconstruction in gradient-field domain using compressed sensing.
AB  - Surface reconstruction from measurements of spatial gradient is an important
      computer vision problem with applications in photometric stereo and shape-from
      shading. In the case of morphologically complex surfaces observed in the presence
      of shadowing and transparency artifacts, a relatively large dense gradient
      measurements may be required for accurate surface reconstruction. Consequently,
      due to hardware limitations of image acquisition devices, situations are possible
      in which the available sampling density might not be sufficiently high to allow
      for recovery of essential surface details. In this paper, the above problem is
      resolved by means of derivative compressed sensing (DCS). DCS can be viewed as a
      modification of the classical CS, which is particularly suited for
      reconstructions involving image/surface gradients. In DCS, a standard CS setting
      is augmented through incorporation of additional constraints arising from some
      intrinsic properties of potential vector fields. We demonstrate that using DCS
      results in reduction in the number of measurements as compared with the standard
      (dense) sampling, while producing estimates of higher accuracy and smaller
      variability as compared with CS-based estimates. The results of this study are
      further supported by a series of numerical experiments.

PMID- 25769158
TI  - Minimum risk wavelet shrinkage operator for Poisson image denoising.
AB  - The pixel values of images taken by an image sensor are said to be corrupted by
      Poisson noise. To date, multiscale Poisson image denoising techniques have
      processed Haar frame and wavelet coefficients--the modeling of coefficients is
      enabled by the Skellam distribution analysis. We extend these results by solving
      for shrinkage operators for Skellam that minimizes the risk functional in the
      multiscale Poisson image denoising setting. The minimum risk shrinkage operator
      of this kind effectively produces denoised wavelet coefficients with minimum
      attainable L2 error.

PMID- 25769159
TI  - Graph-cut based discrete-valued image reconstruction.
AB  - Efficient graph-cut methods have been used with great success for labeling and
      denoising problems occurring in computer vision. Unfortunately, the presence of
      linear image mappings has prevented the use of these techniques in most discrete
      amplitude image reconstruction problems. In this paper, we develop a graph-cut
      based framework for the direct solution of discrete amplitude linear image
      reconstruction problems cast as regularized energy function minimizations. We
      first analyze the structure of discrete linear inverse problem cost functions to
      show that the obstacle to the application of graph-cut methods to their solution
      is the variable mixing caused by the presence of the linear sensing operator. We
      then propose to use a surrogate energy functional that overcomes the challenges
      imposed by the sensing operator yet can be utilized efficiently in existing graph
      cut frameworks. We use this surrogate energy functional to devise a monotonic
      iterative algorithm for the solution of discrete valued inverse problems. We
      first provide experiments using local convolutional operators and show the
      robustness of the proposed technique to noise and stability to changes in
      regularization parameter. Then we focus on nonlocal, tomographic examples where
      we consider limited-angle data problems. We compare our technique with state-of
      the-art discrete and continuous image reconstruction techniques. Experiments show
      that the proposed method outperforms state-of-the-art techniques in challenging
      scenarios involving discrete valued unknowns.

PMID- 25769160
TI  - Penrose demosaicking.
AB  - The Penrose pixel layout, an aperiodic pixel layout in rhombus Penrose tiling,
      has been shown to substantially outperform the existing square pixel layout in
      super-resolution. However, it was tested only on grayscale images. To study its
      performance on color images, we have to reconstruct regular color images from
      Penrose raw images, i.e., images with only one color component at each Penrose
      pixel, resulting in the problem of demosaicking from Penrose pixels. Penrose
      demosaicking is more difficult than regular demosaicking, because none of the
      color components of the reconstructed regular color images are available.
      Therefore, most of the traditional demosaicking methods do not apply. We develop
      a sparse representation-based method for Penrose demosaicking. Extensive
      experiments show that Penrose pixel layout outperforms regular pixel layouts in
      terms of both perceptual evaluation and S-CIELAB. The Penrose pixel layout is
      unique among all irregular layouts because it is uniformly three-colorable and it
      has only two pixel shapes, thick and thin rhombi, making its manufacturing
      relatively easy.

PMID- 25769161
TI  - Generation of spatial orders and space-filling curves.
AB  - Space-filling curves have been found useful for many applications in diverse
      fields. A space-filling curve is a path in a 2(r)*2(r) raster domain, which
      visits each location exactly once. In mathematical terms, space-filling curves
      linearize a 2D integer space, bijectively mapping the space to the integer line.
      An algorithm is presented, which generates a large number of space-filling
      curves/spatial orders. Functions are derived such that the code of each location
      can be calculated from its coordinates and, conversely, a location code can be
      decoded to yield the coordinates. The algorithm first generates generate 4*4
      spatial orders; they subsequently may be scaled up to any desired domain of size
      2(r)*2(r) . The underlying theory of the algorithm, the processes for scaling up,
      encoding, and decoding are described in detail. The curves are generated as a set
      of incongruent curves, followed, if required, by the sets of associated congruent
      curves. A number of space-filling curves are illustrated. 

PMID- 25769162
TI  - Structured sparse priors for image classification.
AB  - Model-based compressive sensing (CS) exploits the structure inherent in sparse
      signals for the design of better signal recovery algorithms. This information
      about structure is often captured in the form of a prior on the sparse
      coefficients, with the Laplacian being the most common such choice (leading to l1
      -norm minimization). Recent work has exploited the discriminative capability of
      sparse representations for image classification by employing class-specific
      dictionaries in the CS framework. Our contribution is a logical extension of
      these ideas into structured sparsity for classification. We introduce the notion
      of discriminative class-specific priors in conjunction with class specific
      dictionaries, specifically the spike-and-slab prior widely applied in Bayesian
      sparse regression. Significantly, the proposed framework takes the burden off the
      demand for abundant training image samples necessary for the success of sparsity
      based classification schemes. We demonstrate this practical benefit of our
      approach in important applications, such as face recognition and object
      categorization. 

PMID- 25769163
TI  - Undersampled face recognition via robust auxiliary dictionary learning.
AB  - In this paper, we address the problem of robust face recognition with
      undersampled training data. Given only one or few training images available per
      subject, we present a novel recognition approach, which not only handles test
      images with large intraclass variations such as illumination and expression. The
      proposed method is also to handle the corrupted ones due to occlusion or
      disguise, which is not present during training. This is achieved by the learning
      of a robust auxiliary dictionary from the subjects not of interest. Together with
      the undersampled training data, both intra and interclass variations can thus be
      successfully handled, while the unseen occlusions can be automatically
      disregarded for improved recognition. Our experiments on four face image datasets
      confirm the effectiveness and robustness of our approach, which is shown to
      outperform state-of-the-art sparse representation-based methods. 

PMID- 25769164
TI  - DERF: distinctive efficient robust features from the biological modeling of the P
      ganglion cells.
AB  - Studies in neuroscience and biological vision have shown that the human retina
      has strong computational power, and its information representation supports
      vision tasks on both ventral and dorsal pathways. In this paper, a new local
      image descriptor, termed distinctive efficient robust features (DERF), is derived
      by modeling the response and distribution properties of the parvocellular
      projecting ganglion cells in the primate retina. DERF features exponential scale
      distribution, exponential grid structure, and circularly symmetric function
      difference of Gaussian (DoG) used as a convolution kernel, all of which are
      consistent with the characteristics of the ganglion cell array found in
      neurophysiology, anatomy, and biophysics. In addition, a new explanation for
      local descriptor design is presented from the perspective of wavelet tight
      frames. DoG is naturally a wavelet, and the structure of the grid points array in
      our descriptor is closely related to the spatial sampling of wavelets. The DoG
      wavelet itself forms a frame, and when we modulate the parameters of our
      descriptor to make the frame tighter, the performance of the DERF descriptor
      improves accordingly. This is verified by designing a tight frame DoG, which
      leads to much better performance. Extensive experiments conducted in the image
      matching task on the multiview stereo correspondence data set demonstrate that
      DERF outperforms state of the art methods for both hand-crafted and learned
      descriptors, while remaining robust and being much faster to compute. 

PMID- 25769165
TI  - Assessment of Foot Trajectory for Human Gait Phase Detection Using Wireless
      Ultrasonic Sensor Network.
AB  - This paper presents a new highly accurate gait phase detection system using
      wearable wireless ultrasonic sensors, which can be used in gait analysis or
      rehabilitation applications. The gait phase detection system uses the foot
      displacement information during walking to extract the following gait phases:
      heel-strike, heel-off, toe-off, and mid-swing. The displacement of foot-mounted
      ultrasonic sensor is obtained from several passive anchors placed at known
      locations by employing local spherical positioning technique, which is further
      enhanced by the combination of recursive Newton-Gauss method and Kalman Filter.
      The algorithm performance is examined by comparing with a commercial optical
      motion tracking system with ten healthy subjects and two foot injured subjects.
      Accurate estimates of gait cycle (with an error of -0.02 +/-0.01 s), stance
      phase(with an error of 0.04+/-0.03 s), and swing phase (with an error of -0.05+/
      0.03 s) compared to the reference system are obtained. We have also investigated
      the influence of walking velocities on the performance of the proposed gait phase
      detection algorithm. Statistical analysis shows that there is no significant
      difference between both systems during different walking speeds. Moreover, we
      have tested and discussed the possibility of the proposed system for clinical
      applications by analyzing the experimental results for both healthy and injured
      subjects. The experiments show that the estimated gait phases have the potential
      to become indicators for sports and rehabilitation engineering. 

PMID- 25769166
TI  - Real-Time Task Discrimination for Myoelectric Control Employing Task-Specific
      Muscle Synergies.
AB  - We present a novel formulation that employs task-specific muscle synergies and
      state-space representation of neural signals to tackle the challenging
      myoelectric control problem for lower arm prostheses. The proposed framework
      incorporates information about muscle configurations, e.g., muscles acting
      synergistically or in agonist/antagonist pairs, using the hypothesis of muscle
      synergies. The synergy activation coefficients are modeled as the latent system
      state and are estimated using a constrained Kalman filter. These task-dependent
      synergy activation coefficients are estimated in real-time from the
      electromyogram (EMG) data and are used to discriminate between various tasks. The
      task discrimination is helped by a post-processing algorithm that uses posterior
      probabilities. The proposed algorithm is robust as well as computationally
      efficient, yielding a decision with > 90% discrimination accuracy in
      approximately 3 ms . The real-time performance and controllability of the
      algorithm were evaluated using the targeted achievement control (TAC) test. The
      proposed algorithm outperformed common machine learning algorithms for single- as
      well as multi-degree-of-freedom (DOF) tasks in both off-line discrimination
      accuracy and real-time controllability (p < 0.01).

PMID- 25769167
TI  - Myoelectric Control System and Task-Specific Characteristics Affect Voluntary Use
      of Simultaneous Control.
AB  - Clinically available myoelectric control does not enable simultaneous
      proportional control of prosthetic degrees of freedom. Multiple studies have
      proposed systems that provide simultaneous control, though few have investigated
      whether subjects voluntarily use simultaneous control or how they implement it.
      Additionally, few studies have explicitly evaluated the effect of providing
      proportional velocity control. The objective of this study was to evaluate
      factors influencing when and how subjects use simultaneous myoelectric control,
      including the ability to proportionally control the velocity and the required
      task precision. Five able-bodied subjects used simultaneous myoelectric control
      systems with and without proportional velocity control in a virtual Fitts' Law
      task. Though subjects used simultaneous control to a substantial degree when
      proportional velocity control was present, they used very little simultaneous
      control when using constant-velocity control. Furthermore, use of simultaneous
      control varied significantly with target distance and width, reflecting a
      strategy of using simultaneous control for gross cursor positioning and
      sequential control for fine corrective movements. These results provide insight
      into how users take advantage of simultaneous control and highlight the need for
      real-time evaluation of simultaneous control algorithms, as the potential benefit
      of providing simultaneous control may be affected by other characteristics of the
      myoelectric control system. 

PMID- 25769169
TI  - Accelerating the Pace of Protein Functional Annotation With Intel Xeon Phi
      Coprocessors.
AB  - Intel Xeon Phi is a new addition to the family of powerful parallel accelerators.
      The range of its potential applications in computationally driven research is
      broad; however, at present, the repository of scientific codes is still
      relatively limited. In this study, we describe the development and benchmarking
      of a parallel version of eFindSite, a structural bioinformatics algorithm for the
      prediction of ligand-binding sites in proteins. Implemented for the Intel Xeon
      Phi platform, the parallelization of the structure alignment portion of eFindSite
      using pragma-based OpenMP brings about the desired performance improvements,
      which scale well with the number of computing cores. Compared to a serial
      version, the parallel code runs 11.8 and 10.1 times faster on the CPU and the
      coprocessor, respectively; when both resources are utilized simultaneously, the
      speedup is 17.6. For example, ligand-binding predictions for 501 benchmarking
      proteins are completed in 2.1 hours on a single Stampede node equipped with the
      Intel Xeon Phi card compared to 3.1 hours without the accelerator and 36.8 hours
      required by a serial version. In addition to the satisfactory parallel
      performance, porting existing scientific codes to the Intel Xeon Phi architecture
      is relatively straightforward with a short development time due to the support of
      common parallel programming models by the coprocessor. The parallel version of
      eFindSite is freely available to the academic community at
      www.brylinski.org/efindsite.

PMID- 25769168
TI  - Robot-Aided Neurorehabilitation: A Pediatric Robot for Ankle Rehabilitation.
AB  - This paper presents the pediAnklebot, an impedance-controlled low-friction,
      backdriveable robotic device developed at the Massachusetts Institute of
      Technology that trains the ankle of neurologically impaired children of ages 6-10
      years old. The design attempts to overcome the known limitations of the lower
      extremity robotics and the unknown difficulties of what constitutes an
      appropriate therapeutic interaction with children. The robot's pilot clinical
      evaluation is on-going and it incorporates our recent findings on the ankle
      sensorimotor control in neurologically intact subjects, namely the speed-accuracy
      tradeoff, the deviation from an ideally smooth ankle trajectory, and the reaction
      time. We used these concepts to develop the kinematic and kinetic performance
      metrics that guided the ankle therapy in a similar fashion that we have done for
      our upper extremity devices. Here we report on the use of the device in at least
      nine training sessions for three neurologically impaired children. Results
      demonstrated a statistically significant improvement in the performance metrics
      assessing explicit and implicit motor learning. Based on these initial results,
      we are confident that the device will become an effective tool that harnesses
      plasticity to guide habilitation during childhood.

PMID- 25769170
TI  - A 16-Channel Nonparametric Spike Detection ASIC Based on EC-PC Decomposition.
AB  - In extracellular neural recording experiments, detecting neural spikes is an
      important step for reliable information decoding. A successful implementation in
      integrated circuits can achieve substantial data volume reduction, potentially
      enabling a wireless operation and closed-loop system. In this paper, we report a
      16-channel neural spike detection chip based on a customized spike detection
      method named as exponential component-polynomial component (EC-PC) algorithm.
      This algorithm features a reliable prediction of spikes by applying a probability
      threshold. The chip takes raw data as input and outputs three data streams
      simultaneously: field potentials, band-pass filtered neural data, and spiking
      probability maps. The algorithm parameters are on-chip configured automatically
      based on input data, which avoids manual parameter tuning. The chip has been
      tested with both in vivo experiments for functional verification and bench-top
      experiments for quantitative performance assessment. The system has a total power
      consumption of 1.36 mW and occupies an area of 6.71 mm (2) for 16 channels. When
      tested on synthesized datasets with spikes and noise segments extracted from in
      vivo preparations and scaled according to required precisions, the chip
      outperforms other detectors. A credit card sized prototype board is developed to
      provide power and data management through a USB port. 

PMID- 25769171
TI  - The PennBMBI: Design of a General Purpose Wireless Brain-Machine-Brain Interface
      System.
AB  - In this paper, a general purpose wireless Brain-Machine-Brain Interface (BMBI)
      system is presented. The system integrates four battery-powered wireless devices
      for the implementation of a closed-loop sensorimotor neural interface, including
      a neural signal analyzer, a neural stimulator, a body-area sensor node and a
      graphic user interface implemented on the PC end. The neural signal analyzer
      features a four channel analog front-end with configurable bandpass filter, gain
      stage, digitization resolution, and sampling rate. The target frequency band is
      configurable from EEG to single unit activity. A noise floor of 4.69 MUVrms is
      achieved over a bandwidth from 0.05 Hz to 6 kHz. Digital filtering, neural
      feature extraction, spike detection, sensing-stimulating modulation, and
      compressed sensing measurement are realized in a central processing unit
      integrated in the analyzer. A flash memory card is also integrated in the
      analyzer. A 2-channel neural stimulator with a compliance voltage up to +/- 12 V
      is included. The stimulator is capable of delivering unipolar or bipolar, charge
      balanced current pulses with programmable pulse shape, amplitude, width, pulse
      train frequency and latency. A multi-functional sensor node, including an
      accelerometer, a temperature sensor, a flexiforce sensor and a general sensor
      extension port has been designed. A computer interface is designed to monitor,
      control and configure all aforementioned devices via a wireless link, according
      to a custom designed communication protocol. Wireless closed-loop operation
      between the sensory devices, neural stimulator, and neural signal analyzer can be
      configured. The proposed system was designed to link two sites in the brain,
      bridging the brain and external hardware, as well as creating new sensory and
      motor pathways for clinical practice. Bench test and in vivo experiments are
      performed to verify the functions and performances of the system.

PMID- 25769172
TI  - Adaptive Robust Output Feedback Control for a Marine Dynamic Positioning System
      Based on a High-Gain Observer.
AB  - This paper develops an adaptive robust output feedback control scheme for
      dynamically positioned ships with unavailable velocities and unknown dynamic
      parameters in an unknown time-variant disturbance environment. The controller is
      designed by incorporating the high-gain observer and radial basis function (RBF)
      neural networks in vectorial backstepping method. The high-gain observer provides
      the estimations of the ship position and heading as well as velocities. The RBF
      neural networks are employed to compensate for the uncertainties of ship
      dynamics. The adaptive laws incorporating a leakage term are designed to estimate
      the weights of RBF neural networks and the bounds of unknown time-variant
      environmental disturbances. In contrast to the existing results of dynamic
      positioning (DP) controllers, the proposed control scheme relies only on the ship
      position and heading measurements and does not require a priori knowledge of the
      ship dynamics and external disturbances. By means of Lyapunov functions, it is
      theoretically proved that our output feedback controller can control a ship's
      position and heading to the arbitrarily small neighborhood of the desired target
      values while guaranteeing that all signals in the closed-loop DP control system
      are uniformly ultimately bounded. Finally, simulations involving two ships are
      carried out, and simulation results demonstrate the effectiveness of the proposed
      control scheme. 

PMID- 25769173
TI  - Emotional Multiagent Reinforcement Learning in Spatial Social Dilemmas.
AB  - Social dilemmas have attracted extensive interest in the research of multiagent
      systems in order to study the emergence of cooperative behaviors among selfish
      agents. Understanding how agents can achieve cooperation in social dilemmas
      through learning from local experience is a critical problem that has motivated
      researchers for decades. This paper investigates the possibility of exploiting
      emotions in agent learning in order to facilitate the emergence of cooperation in
      social dilemmas. In particular, the spatial version of social dilemmas is
      considered to study the impact of local interactions on the emergence of
      cooperation in the whole system. A double-layered emotional multiagent
      reinforcement learning framework is proposed to endow agents with internal
      cognitive and emotional capabilities that can drive these agents to learn
      cooperative behaviors. Experimental results reveal that various network
      topologies and agent heterogeneities have significant impacts on agent learning
      behaviors in the proposed framework, and under certain circumstances, high levels
      of cooperation can be achieved among the agents. 

PMID- 25769174
TI  - Nonsmooth Neural Network for Convex Time-Dependent Constraint Satisfaction
      Problems.
AB  - This paper introduces a nonsmooth (NS) neural network that is able to operate in
      a time-dependent (TD) context and is potentially useful for solving some classes
      of NS-TD problems. The proposed network is named nonsmooth time-dependent network
      (NTN) and is an extension to a TD setting of a previous NS neural network for
      programming problems. Suppose C(t), t >= 0, is a nonempty TD convex feasibility
      set defined by TD inequality constraints. The constraints are in general NS
      (nondifferentiable) functions of the state variables and time. NTN is described
      by the subdifferential with respect to the state variables of an NS-TD barrier
      function and a vector field corresponding to the unconstrained dynamics. This
      paper shows that for suitable values of the penalty parameter, the NTN dynamics
      displays two main phases. In the first phase, any solution of NTN not starting in
      C(0) at t=0 is able to reach the moving set C(.) in finite time th , whereas in
      the second phase, the solution tracks the moving set, i.e., it stays within C(t)
      for all subsequent times t >= t(h). NTN is thus able to find an exact feasible
      solution in finite time and also to provide an exact feasible solution for
      subsequent times. This new and peculiar dynamics displayed by NTN is potentially
      useful for addressing some significant TD signal processing tasks. As an
      illustration, this paper discusses a number of examples where NTN is applied to
      the solution of NS-TD convex feasibility problems.

PMID- 25769175
TI  - Competition and Collaboration in Cooperative Coevolution of Elman Recurrent
      Neural Networks for Time-Series Prediction.
AB  - Collaboration enables weak species to survive in an environment where different
      species compete for limited resources. Cooperative coevolution (CC) is a nature
      inspired optimization method that divides a problem into subcomponents and
      evolves them while genetically isolating them. Problem decomposition is an
      important aspect in using CC for neuroevolution. CC employs different problem
      decomposition methods to decompose the neural network training problem into
      subcomponents. Different problem decomposition methods have features that are
      helpful at different stages in the evolutionary process. Adaptation,
      collaboration, and competition are needed for CC, as multiple subpopulations are
      used to represent the problem. It is important to add collaboration and
      competition in CC. This paper presents a competitive CC method for training
      recurrent neural networks for chaotic time-series prediction. Two different
      instances of the competitive method are proposed that employs different problem
      decomposition methods to enforce island-based competition. The results show
      improvement in the performance of the proposed methods in most cases when
      compared with standalone CC and other methods from the literature. 

PMID- 25769176
TI  - Real-Time Prediction of Neurally Mediated Syncope.
AB  - Neurally mediated syncope (NMS) patients suffer from sudden loss of
      consciousness, which is associated with a high rate of falls and hospitalization.
      NMS negatively impacts a subject's quality of life and is a growing cost issue in
      our aging society, as its incidence increases with age. In this paper, we present
      a solution for prediction of NMS, which is based on the analysis of the
      electrocardiogram (ECG) and photoplethysmogram (PPG) alone. Several parameters
      extracted from ECG and PPG, associated with reflectory mechanisms underlying NMS
      in previous publications, were combined in a single algorithm to detect impending
      syncope. The proposed algorithm was evaluated in a population of 43 subjects. The
      feature selection, distance metric selection, and optimal threshold were
      performed in a subset of 30 patients, while the remaining data from 13 patients
      were used to test the final solution. Additionally, a leave-one-out cross
      validation scheme was also used to evaluate the performance of the proposed
      algorithm yielding the following results: sensitivity (SE)--95.2%; specificity
      (SP)--95.4%; positive predictive value (PPV)--90.9%; false-positive rate per hour
      (FPRh)-0.14 h(-1), and prediction time (aPTime)--116.4 s. 

PMID- 25769177
TI  - A Conjugate Exponential Model for Cancer Tissue Heterogeneity.
AB  - The diagnosis and treatment of cancer is made difficult by the heterogeneous
      nature of the cell population. Determining its compositional breakup from
      measurements of various measurable traits (such as gene expression measurements)
      is an important problem in the field of cancer diagnosis and treatment. In
      addition, the computational aspect of the problem also needs attention. The
      processing of the collected data must be done as efficiently as possible in terms
      of computational speed and memory requirements. The use of Markov chain Monte
      Carlo methods is time consuming, and hence, other methods need to be used for the
      analysis. In this paper, we develop a model for heterogeneous cancer tissue,
      which uses quantitative polymerase chain reaction gene expression data to
      determine the compositional breakup of cell populations in the heterogeneous
      tissue. We develop a fast algorithm for the model using variational methods and
      demonstrate its use on synthetic and real-world gene expression data collected
      from fibroblasts and compare the performance of the algorithm with other methods
      such as Markov chain Monte Carlo and expectation maximization. 

PMID- 25769178
TI  - A Multiobjective Genetic Programming-Based Ensemble for Simultaneous Feature
      Selection and Classification.
AB  - We present an integrated algorithm for simultaneous feature selection (FS) and
      designing of diverse classifiers using a steady state multiobjective genetic
      programming (GP), which minimizes three objectives: 1) false positives (FPs); 2)
      false negatives (FNs); and 3) the number of leaf nodes in the tree. Our method
      divides a c -class problem into c binary classification problems. It evolves c
      sets of genetic programs to create c ensembles. During mutation operation, our
      method exploits the fitness as well as unfitness of features, which dynamically
      change with generations with a view to using a set of highly relevant features
      with low redundancy. The classifiers of i th class determine the net
      belongingness of an unknown data point to the i th class using a weighted voting
      scheme, which makes use of the FP and FN mistakes made on the training data. We
      test our method on eight microarray and 11 text data sets with diverse number of
      classes (from 2 to 44), large number of features (from 2000 to 49 151), and high
      feature-to-sample ratio (from 1.03 to 273.1). We compare our method with a bi
      objective GP scheme that does not use any FS and rule size reduction strategy. It
      depicts the effectiveness of the proposed FS and rule size reduction schemes.
      Furthermore, we compare our method with four classification methods in
      conjunction with six features selection algorithms and full feature set. Our
      scheme performs the best for 380 out of 474 combinations of data sets, algorithm
      and FS method. 

PMID- 25769179
TI  - Beyond the Mean: Quantile Regression to Explore the Association of Air Pollution
      with Gene-Specific Methylation in the Normative Aging Study.
AB  - BACKGROUND: Air pollution has been related to mean changes in outcomes, including
      DNA methylation. However, mean regression analyses may not capture associations
      that occur primarily in the tails of the outcome distribution. OBJECTIVES: In
      this study, we examined whether the association between particulate air pollution
      and DNA methylation differs across quantiles of the methylation distribution. We
      focused on methylation of candidate genes related to coagulation and
      inflammation: coagulation factor III (F3), intercellular adhesion molecule 1
      (ICAM-1), interferon gamma (IFN-gamma), interleukin-6 (IL-6), and toll-like
      receptor 2 (TRL-2). METHODS: We measured gene-specific blood DNA methylation
      repeatedly in 777 elderly men participating in the Normative Aging Study (1999
      2010). We fit quantile regressions for longitudinal data to investigate whether
      the associations of particle number, PM2.5 (diameter <= 2.5 MUm)black carbon, and
      PM2.5 mass concentrations (4-week moving average) with DNA methylation [expressed
      as the percentage of methylated cytosines over the sum of methylated and
      unmethylated cytosines at position 5 (%5mC)] varied across deciles of the
      methylation distribution. We reported the quantile regression coefficients that
      corresponded to absolute differences in DNA methylation (expressed in %5mC)
      associated with an interquartile range increase in air pollution concentration.
      RESULTS: Interquartile range increases in particle number, PM2.5 black carbon,
      and PM2.5 mass concentrations were associated with significantly lower
      methylation in the lower tails of the IFN-gamma and ICAM-1 methylation
      distributions. For instance, a 3.4-MUg/m3 increase in PM2.5 mass concentration
      was associated with a 0.18%5mC (95% CI: -0.30, -0.06) decrease on the 20th
      percentile of ICAM-1 methylation, but was not significantly related to the 80th
      percentile (estimate: 0.07%5mC, 95% CI: -0.09, 0.24). CONCLUSIONS: In our study
      population of older men, air pollution exposures were associated with a left
      shift in the lower tails of the IFN-gamma and ICAM-1 methylation distributions.

PMID- 25769180
TI  - Measured Prenatal and Estimated Postnatal Levels of Polychlorinated Biphenyls
      (PCBs) and ADHD-Related Behaviors in 8-Year-Old Children.
AB  - BACKGROUND: Epidemiologic studies of postnatal PCB exposure and behavior have not
      reported consistent evidence of adverse associations, possibly because of
      challenges in exposure estimation. We previously developed a pharmacokinetic
      model to improve estimation of children's PCB exposure. OBJECTIVES: We aimed to
      assess whether estimated serum PCB levels in infancy are associated with
      attention deficit/hyperactivity disorder (ADHD)-related behaviors at 8 years of
      age among children whose cord serum PCB levels were previously shown to be
      associated with ADHD-related behaviors. METHODS: We used a pharmacokinetic model
      to estimate monthly serum polychlorinated biphenyl (PCB)-153 levels in 441
      infants (ages 1-12 months) based on parameters such as breastfeeding and cord
      serum PCB-153 levels. Behavior was evaluated at age 8 using the Conners' Rating
      Scale for Teachers (CRS-T). Associations between PCB-153 levels and ADHD-related
      CRS-T indices were assessed using multivariable quantile regression at the 50th
      and 75th percentiles of CRS-T scores, where higher percentiles reflect more
      adverse behaviors. RESULTS: Cord serum PCB-153 levels (median, 38 ng/g lipids)
      were associated with ADHD-related behaviors, although statistical significance
      was observed with quantile regression models only at the 75th percentile.
      Associations with postnatal exposure estimates were attenuated. For example,
      hyperactive-impulsive behavior scores at age 8 years were 0.9 points (95% CI:
      0.2, 2.5), 0.5 points (95% CI: 0.3, 2.3), and 0.3 points (95% CI: -0.2, 1.5)
      higher in association with interquartile range increases in serum PCB-153 at
      birth, 2 months, and 12 months of age, respectively. CONCLUSIONS: Associations
      between estimated postnatal PCB-153 exposures and ADHD-related behaviors at 8
      years of age were weaker than associations with PCB-153 concentrations measured
      in cord serum at birth. CITATION: Verner MA, Hart JE, Sagiv SK, Bellinger DC,
      Altshul LM, Korrick SA. 2015. Measured prenatal and estimated postnatal levels of
      polychlorinated biphenyls (PCBs) and ADHD-related behaviors in 8-year-old
      children. Environ Health Perspect 123:888-894;
      http://dx.doi.org/10.1289/ehp.1408084.

PMID- 25769181
TI  - Benzo[a]pyrene-induced cell cycle progression occurs via ERK-induced Chk1 pathway
      activation in human lung cancer cells.
AB  - Benzo[a]pyrene (B[a]P) is a potent lung carcinogen derived from tobacco smoking
      and environmental contamination. This study aimed to investigate the signal
      transduction pathway responsible for B[a]P-induced non-small cell lung cancer
      (NSCLC) development. We exposed the human NSCLC cell lines Calu-1, CL3, H1299,
      CH27, H23, and H1355 to B[a]P and assessed cell cycle progression using flow
      cytometry. Expression of cell cycle mediators was measured using Western blot
      analyses and electrophoretic mobility shift assays (EMSAs). B[a]P exposure
      dramatically induced S-phase accumulation in H1355 cells. Phospho-p53 (Ser15 and
      Ser20), phospho-ERK, phospho-p38, and Bax were significantly increased in H1355
      cells whereas phospho-Rb was decreased in these cells. In addition, B[a]P induced
      phosphorylation of checkpoint kinase-1 (Chk1) but not Chk2. EMSA experiments
      revealed a slower migrating band after c-Myc bound the E-box in response to B[a]P
      treatment, which was abolished upon the addition of the ERK inhibitor PD98059 in
      H1355 cells. Phospho-ERK inhibition and dominant negative mutant Chk1 expression
      reversed B[a]P-induced S phase accumulation and downregulated phospho-Chk1 and
      phospho-ERK expression. Taken together, these results suggest that activation of
      ERK and its downstream mediator Chk1 may contribute to B[a]P-induced S phase
      accumulation in H1355 cells. The results could help in the development of lung
      cancer treatments that target the Chk1 pathway through ERK. 

PMID- 25769182
TI  - piRNA-mediated transposon regulation and the germ-line mutation rate in
      Drosophila melanogaster males.
AB  - Transposons, especially retrotransposons, are abundant in the genome of
      Drosophila melanogaster. These mobile elements are regulated by small RNAs that
      interact with the Piwi family of proteins-the piwi-interacting or piRNAs. The
      Piwi proteins are encoded by the genes argonaute3 (ago3), aubergine (aub), and
      piwi. Heterochromatin Protein 1 (HP1), a chromatin-organizing protein encoded by
      the Suppressor of variegation 205 [Su(var)205] gene, also plays a role in this
      regulation. To assess the mutational impact of weakening the system for
      transposon regulation, we measured the frequency of recessive X-linked lethal
      mutations occurring in the germ lines of males from stocks that were heterozygous
      for mutant alleles of the ago3, aub, piwi, or Su(var)205 genes. These mutant
      alleles are expected to deplete the wild-type proteins encoded by these genes by
      as much as 50%. The mutant alleles of piwi and Su(var)205 significantly increased
      the X-linked lethal mutation frequency, whereas the mutant alleles of ago3 did
      not. An increased mutation frequency was also observed in males from one of two
      mutant aub stocks, but this increase may not have been due to the aub mutant. The
      increased mutation frequency caused by depleting Piwi or HP1suggests that
      chromatin-organizing proteins play important roles in minimizing the germ-line
      mutation rate, possibly by stabilizing the structure of the heterochromatin in
      which many transposons are situated. 

PMID- 25769183
TI  - The effects of extremely low frequency magnetic fields on mutation induction in
      mice.
AB  - The growing human exposure to extremely low frequency (ELF) magnetic fields has
      raised a considerable concern regarding their genotoxic effects. The aim of this
      study was to evaluate the in vivo effects of ELF magnetic fields irradiation on
      mutation induction in the germline and somatic tissues of male mice. Seven week
      old BALB/c*CBA/Ca F1 hybrid males were exposed to 10, 100 or 300MUT of 50Hz
      magnetic fields for 2 or 15h. Using single-molecule PCR, the frequency of
      mutation at the mouse Expanded Simple Tandem Repeat (ESTR) locus Ms6-hm was
      established in sperm and blood samples of exposed and matched sham-treated males.
      ESTR mutation frequency was also established in sperm and blood samples taken
      from male mice exposed to 1Gy of acute X-rays. The frequency of ESTR mutation in
      DNA samples extracted from blood of mice exposed to magnetic fields did not
      significantly differ from that in sham-treated controls. However, there was a
      marginally significant increase in mutation frequency in sperm but this was not
      dose-dependent. In contrast, acute exposure X-rays led to significant increases
      in mutation frequency in sperm and blood of exposed males. The results of our
      study suggest that, within the range of doses analyzed here, the in vivo
      mutagenic effects of ELF magnetic fields are likely to be minor if not
      negligible. 

PMID- 25769184
TI  - Modulation of modeled microgravity on radiation-induced bystander effects in
      Arabidopsis thaliana.
AB  - Both space radiation and microgravity have been demonstrated to have inevitable
      impact on living organisms during space flights and should be considered as
      important factors for estimating the potential health risk for astronauts.
      Therefore, the question whether radiation effects could be modulated by
      microgravity is an important aspect in such risk evaluation. Space particles at
      low dose and fluence rate, directly affect only a fraction of cells in the whole
      organism, which implement radiation-induced bystander effects (RIBE) in cellular
      response to space radiation exposure. The fact that all of the RIBE experiments
      are carried out in a normal gravity condition bring forward the need for evidence
      regarding the effect of microgravity on RIBE. In the present study, a two
      dimensional rotation clinostat was adopted to demonstrate RIBE in microgravity
      conditions, in which the RIBE was assayed using an experimental system of root
      localized irradiation of Arabidopsis thaliana (A. thaliana) plants. The results
      showed that the modeled microgravity inhibited significantly the RIBE-mediated up
      regulation of expression of the AtRAD54 and AtRAD51 genes, generation of reactive
      oxygen species (ROS) and transcriptional activation of multicopy P35S:GUS, but
      made no difference to the induction of homologous recombination by RIBE, showing
      divergent responses of RIBE to the microgravity conditions. The time course of
      interaction between the modeled microgravity and RIBE was further investigated,
      and the results showed that the microgravity mainly modulated the processes of
      the generation or translocation of the bystander signal(s) in roots. 

PMID- 25769185
TI  - Cyclobutane pyrimidine dimers photolyase from extremophilic microalga: remarkable
      UVB resistance and efficient DNA damage repair.
AB  - Bacteria living in the Antarctic region have developed several adaptive features
      for growth and survival under extreme conditions. Chlamydomonas sp. ICE-Lis well
      adapted to high levels of solar UV radiation. A putative photolyase was
      identified in the Chlamydomonas sp. ICE-L transcriptome. The complete cDNA
      sequence was obtained by RACE-PCR. This PHR encoding includes a polypeptide of
      579 amino acids with clear photolyase signatures belonging to class II CPD
      photolyases, sharing a high degree of homology with Chlamydomonas reinhardtii
      (68%). Real-time PCR was performed to investigate the potential DNA damage and
      responses following UVB exposure. CPD photolyase mRNA expression level increased
      over 50-fold in response to UVB radiation for 6h. Using photolyase
      complementation assay, we demonstrated that DNA photolyase increased photo-repair
      more than 116-fold in Escherichia coli strain SY2 under 100MUw/cm(2) UVB
      radiation. To determine whether photolyase is active in vitro, CPD photolyase was
      over-expressed. It was shown that pyrimidine dimers were split by the action of
      PHR2. This study reports the unique structure and high activity of the enzyme.
      These findings are relevant for further understanding of molecular mechanisms of
      photo-reactivation, and will accelerate the utilization of photolyase in the
      medical field. 

PMID- 25769186
TI  - Target irradiation induced bystander effects between stem-like and non stem-like
      cancer cells.
AB  - Tumors are heterogeneous in nature and consist of multiple cell types. Among
      them, cancer stem-like cells (CSCs) are suggested to be the principal cause of
      tumor metastasis, resistance and recurrence. Therefore, understanding the
      behavior of CSCs in direct and indirect irradiations is crucial for clinical
      radiotherapy. Here, the CSCs and their counterpart non stem-like cancer cells
      (NSCCs) in human HT1080 fibrosarcoma cell line were sorted and labeled, then the
      two cell subtypes were mixed together and chosen separately to be irradiated via
      a proton microbeam. The radiation-induced bystander effect (RIBE) between the
      CSCs and NSCCs was measured by imaging 53BP1 foci, a widely used indicator for
      DNA double strand break (DSB). CSCs were found to be less active than NSCCs in
      both the generation and the response of bystander signals. Moreover, the nitric
      oxide (NO) scavenger c-PTIO can effectively alleviate the bystander effect in
      bystander NSCCs but not in bystander CSCs, indicating a difference of the two
      cell subtypes in NO signal response. To our knowledge, this is the first report
      shedding light on the RIBE between CSCs and NSCCs, which might contribute to a
      further understanding of the out-of-field effect in cancer radiotherapy. 

PMID- 25769187
TI  - The Belgian, French and Dutch midwife on trial: A critical case study.
AB  - OBJECTIVE: to develop juridical recommendations in order to avoid midwifery
      medical liability when providing intrapartum care. DESIGN: case law of the past
      40 years concerning midwifery medical negligence when assisting labour/delivery
      in a hospital was analysed. Databases used were Jura and Judit (Belgium),
      Legifrance, Juricaf and Dalloz (France) and Recht, Rechtspraak (The Netherlands).
      A minority of cases were retrieved through contacts with insurance companies
      (only Belgium), lawyers and courts. SETTING: law suits in Belgium, France and The
      Netherlands. FINDINGS: the 100 analysed cases could be categorised into four
      types. The judicial assessment was focused on three domains of expertise of the
      midwife. Most cases involved interpreting fetal monitoring (47%), followed by
      recognising a specific pathology (32%) and responding to a complication (12%). A
      fourth type of case concerned exceeding the boundaries of the legal competencies
      of the midwife (9%). KEY CONCLUSIONS: not identifying fetal distress through
      fetal monitoring was the most common cause of midwifery liability (15/47),
      followed by not recognising the symptoms of a pathology (10/32), particularly
      placental abruption and uterine rupture. Also an inaccurate response to
      complications (3/12) and evidently exceeding the professional competencies
      involved midwifery liability. IMPLICATIONS FOR PRACTICE: achieving
      cardiotocograph interpretation skills is the first and most important
      recommendation. In pathologic cases, the midwife should immediately refer to an
      obstetrician, without any hesitation. The third recommendation is working in a
      team with the obstetrician. If the midwife has reasonable (evidence-based) doubts
      about the practice of the obstetrician, she should insist on re-assessment with
      respect to the boundaries of her competencies. The fourth recommendation concerns
      practising with knowledge of the client's/patient's medical record and updating
      the record with performances and observations. Consciously choosing the type of
      medical intervention in urgent cases of pathology is the final recommendation.

PMID- 25769188
TI  - Does outpatient physical therapy with the aim of improving health-related
      physical fitness influence the level of physical activity in patients with long
      term musculoskeletal conditions?
AB  - OBJECTIVE: To evaluate any change in self-reported level of physical activity in
      patients receiving a general physical exercise programme in addition to disease
      specific physiotherapy treatment. DESIGN: Pre-post-intervention study. SETTING:
      Outpatient physiotherapy clinics. PARTICIPANTS: One hundred and ninety patients
      with long-term musculoskeletal conditions attending outpatient physiotherapy were
      recruited from seven physiotherapy clinics. INTERVENTIONS: Physiotherapy
      including disease-specific modalities and a general individually tailored
      exercise programme. Patients were evaluated at baseline and at the end of the
      programme. MAIN OUTCOME MEASURES: International Physical Activity Questionnaire
      short form (IPAQ-sf) and COOP WONCA functional assessment charts. RESULTS: Forty
      two patients were excluded from the analysis because they did not complete the
      IPAQ-sf correctly or dropped out during the treatment period. There was a
      significant increase in the number of metabolic equivalent task (MET)-min/week
      for vigorous and moderate-intensity activities, walking and total physical
      activity. The number of exercise sessions per week increased from 1.8 [standard
      deviation (SD) 0.9] to 2.2 (SD 1.2) (P=0.001). The proportion of patients with a
      low level of physical activity decreased by 12%, and the proportion of the
      participants who did not/could not exercise decreased from 26% to 8%. The COOP
      WONCA charts showed significant improvements in the physical fitness, feelings,
      daily activities and social activities items. CONCLUSION: A significant increase
      was found in the number of MET-min/week for all activity levels. Therefore, a
      general physical exercise programme initiated by a physiotherapist led to a
      positive change in level of physical activity.

PMID- 25769189
TI  - Identifying potential moderators for response to treatment in low back pain: A
      systematic review.
AB  - BACKGROUND: Identifying which patients with non-specific low back pain are likely
      to gain the greatest benefit from different treatments is an important research
      priority. Few studies are large enough to produce data on sub-group effects from
      different treatments. Data from existing large studies may help identify
      potential moderators to use in future individual patient data meta-analyses.
      OBJECTIVE: To systematically review papers of therapist delivered interventions
      for low back pain to identify potential moderators to inform an individual
      patient data meta-analysis. DATA SOURCES: We searched MEDLINE, EMBASE, Web of
      Science and Citation Index and Cochrane Register of Controlled Trials
      (CENTRALhttp://www.cochrane.org/editorial-and-publishing-policy-resource/cochrane
      central-register-controlled-trials-central) for relevant papers. DATA EXTRACTION
      AND DATA SYNTHESIS: We screened for randomised controlled trials with >=500 or
      more participants, and cohort studies of >=1000 or more participants. We examined
      all publications related to these studies for any reported moderator analyses.
      Two reviewers independently did risk of bias assessment of main results and
      quality assessment of any moderator analyses. RESULTS: We included four
      randomised trials (n=7208). Potential moderators with strong evidence (p<0.05) in
      one or more studies were age, employment status and type, back pain status,
      narcotic medication use, treatment expectations and education. Potential
      moderators with weaker evidence (0.05<p<=0.20) included gender, psychological
      distress, pain/disability and quality of life. CONCLUSION: There are insufficient
      robust data on moderators to be useful in clinical practice. This review has
      identified some important potential moderators of treatment effect worthy of
      testing in future confirmatory analyses.

PMID- 25769190
TI  - [Need for orthodontic treatment among Brazilian adolescents: evaluation based on
      public health].
AB  - OBJECTIVE: To identify the prevalence and the severity of malocclusions and to
      analyze factors associated with the need for orthodontic treatment of Brazilian
      adolescents. METHODS: This exploratory, cross-sectional study was carried out
      based on secondary data from the national epidemiological survey on oral health
      in Brazil (2002-2003). Socio-demographic conditions, self-perception, and the
      existence and degree of malocclusion, using the Dental Aesthetic Index, were
      evaluated in 16,833 adolescent Brazilians selected by probabilistic sample by
      conglomerates. The dependent variable - need orthodontic treatment - was
      estimated from the severity of malocclusion. The magnitude and direction of the
      association in bivariate and multivariate analyzes from a Robust Poisson
      regression was estimated. RESULTS: The majority of the adolescents needed
      orthodontic treatment (53.2%). In the multivariate analysis, the prevalence of
      the need for orthodontic treatment was larger among females, non-whites, those
      that perceived a need for treatment, and those that perceived their appearance as
      normal, bad, or very bad. The need for orthodontic treatment was smaller among
      those that lived in the Northeast and Central West macro-regions compared to
      those living in Southeast Brazil and it was also smaller among those that
      perceived their chewing to be normal or their oral health to be bad or very bad.
      CONCLUSIONS: There was a high prevalence of orthodontic treatment need among
      adolescents in Brazil and this need was associated with demographic and
      subjective issues. The high prevalence of orthodontic needs in adolescents is a
      challenge to the goals of Brazil's universal public health system.

PMID- 25769191
TI  - Advances in the therapeutic use of mammalian target of rapamycin (mTOR)
      inhibitors in dermatology.
AB  - Significant developments in the use of mammalian target of rapamycin (mTOR)
      inhibitors (mTORIs) as immunosuppressant and antiproliferative agents have been
      made. Recent advances in the understanding of the mTOR signaling pathway and its
      downstream effects on tumorigenesis and vascular proliferation have broadened the
      clinical applications of mTORIs in many challenging disorders such as tuberous
      sclerosis complex, pachyonychia congenita, complex vascular anomalies, and
      inflammatory dermatoses. Systemic mTORI therapy has shown benefits in these
      areas, but is associated with significant side effects that sometimes necessitate
      drug holidays. To mitigate the side effects of systemic mTORIs for dermatologic
      applications, preliminary work to assess the potential of percutaneous therapy
      has been performed, and the evidence suggests that percutaneous delivery of
      mTORIs may allow for effective long-term therapy while avoiding systemic
      toxicities. Additional large placebo-controlled, double-blinded, randomized
      studies are needed to assess the efficacy, safety, duration, and tolerability of
      topical treatments. The objective of this review is to provide updated
      information on the novel use of mTORIs in the management of many cutaneous
      disorders. 

PMID- 25769192
TI  - Risk of subsequent melanoma after melanoma in situ and invasive melanoma: a
      population-based study from 1973 to 2011.
AB  - BACKGROUND: Patients with melanoma in situ are at an increased risk of subsequent
      melanoma compared with the general population, but the risk of subsequent
      melanoma after initial melanoma in situ versus after initial invasive melanoma is
      not known. OBJECTIVE: We sought to compare the risk of subsequent melanoma in the
      cohort whose first cancer was melanoma in situ to the risk in the cohort whose
      first cancer was invasive melanoma. METHODS: In this cohort study, we identified
      individuals whose first cancer was either melanoma in situ or invasive melanoma
      from the Surveillance, Epidemiology, and End Results (SEER) program between 1973
      and 2011 and used Cox proportional hazards models for comparison. RESULTS:
      Compared with the invasive melanoma cohort, the melanoma in situ cohort was more
      likely to develop subsequent melanoma of any stage after 2 years, subsequent
      invasive melanoma after 10 years, and subsequent melanoma in situ at all the time
      points (P < .001, P = .003, P < .001, respectively). LIMITATIONS: Underreporting
      of melanomas, particularly melanoma in situ cases, and missing cases of
      subsequent melanomas as a result of patient migration from the SEER registry
      areas could affect results. CONCLUSION: Given the increased long-term risk of
      subsequent melanoma in the melanoma in situ cohort, the patients with melanoma in
      situ diagnosis may benefit from a long-term surveillance for subsequent
      melanomas.

PMID- 25769193
TI  - Survival time of calves with positive BVD virus results born during the voluntary
      phase of the Irish eradication programme.
AB  - A retrospective case-control study was undertaken to investigate the temporal
      pattern of, and factors associated with, the survival of BVD virus-positive
      calves, identified between January and July 2012 during the voluntary phase of
      the Irish national eradication programme. Potential statuses for case and control
      calves consisted of: alive in birth herd; slaughtered; sold; dead (due to culling
      or death from natural causes and termed 'involuntary removal'). An initial
      comparison of cases and controls found significant differences between the
      outcomes for cases and controls and also between cases in relation to herd type
      (beef, dairy, dual purpose), sex, age and test status (BVDPOS - no confirmatory
      test; BVDPI - positive on confirmatory test). Key differences included a higher
      level of case animals still alive in, or slaughtered from, beef herds, a greater
      proportion of BVDPI animals being retained relative to those with a BVDPOS status
      and a significantly lower slaughter weight (89 kg) for case animals relative to
      controls. Separate multivariable models were constructed for dairy and beef
      cases. In the final dairy model breed (Jersey or non-Jersey), county and BVD
      status were retained, with the last two found to be time-varying covariates with
      significant changes in hazard ratios (HR) over time. In the beef model, herd
      size, county and BVD status were retained, with the HR for the last two factors
      again varying significantly over time. With the exception of the addition of the
      number of BVD positive calves in the herd to the dairy model, the same factors
      were identified when models were restricted to the first 90 days following the
      birth of case animals. A greater knowledge and understanding of all of these
      factors will allow refinement of programme communications and incentives to
      encourage prompt removal of PI calves from all sectors of the Irish breeding herd
      during the compulsory phase of the national eradication programme.

PMID- 25769194
TI  - Light Harvesting and Charge Recombination in CH3NH3PbI3 Perovskite Solar Cells
      Studied by Hole Transport Layer Thickness Variation.
AB  - A tailored optimization of perovskite solar cells requires a detailed
      understanding of the processes limiting the device efficiency. Here, we study the
      role of the hole transport layer (HTL) spiro-MeOTAD and its thickness in a
      mesoscopic TiO2-based solar cell architecture. We find that a sufficiently thick
      (200 nm) HTL not only increases the charge carrier collection efficiency but also
      the light harvesting efficiency. This is due to an enhanced reflection of a
      smooth HTL/Au-electrode interface. The rough CH3NH3PbI3 perovskite surface
      requires an HTL thickness of >400 nm to avoid surface recombination and guarantee
      a high open-circuit voltage. Analyses of the electroluminescence efficiency and
      the diode ideality factor show that the open-circuit voltage becomes completely
      limited by trap-assisted recombination in the perovskite for a thick HTL. Thus,
      spiro-MeOTAD is a very good HTL choice from the device physics' point of view.
      The fill factor analyzed by the Suns-Voc method is not transport limited, but
      trap-recombination limited as well. Consequently, a further optimization of the
      device has to focus on defects in the polycrystalline perovskite film. 

PMID- 25769195
TI  - [Evaluation of a supervised physical exercise program in sedentary patients over
      65 years with type 2 diabetes mellitus].
AB  - OBJECTIVE: To analyze whether an exercise program can modify glycated hemoglobin
      (HbA1c), blood pressure (BP), body mass index (BMI), lipids, cardiovascular risk
      profile (CVR), self-perceived health status (SHS), and pharmaceutical expenditure
      (PE). DESIGN: A randomized, single blind, controlled trial. INTERVENTION: program
      of supervised aerobic physical exercise. Analysis by intention to treat.
      LOCATION: Primary Care: 2 rural health areas. Health Area of Navalmoral. Caceres.
      Extremadura. Spain. PARTICIPANTS: 100 type 2 diabetic patients, aged 65 to 80
      years, sedentary. Distribution: 50% control group (CG) and 50% intervention group
      (IG). Abandoned 12%. INTERVENTION: monitored aerobic exercise: 40minutes, 2
      days/week, 3 months. KEY MEASURES: HbA1c, BP, BMI, lipid, CVR, SHS, PE.
      Complications during exercise. RESULTS: There were post-intervention differences
      between groups in HbA1c, BP, BMI, cholesterol and SHS. In the IG, there was a
      significant decrease in; HbA1c: 0.2+/-0.4% (95% CI: 0.1 to 0.3), systolic BP:
      11.8+/-8.5mmHg (95% CI: 5.1 to 11.9), BMI: 0.5+/-1 (95% CI: 0.2 to 0.8), total
      cholesterol: 14+/-28.2mg/dl (95% CI: 5.9 to 22.2), LDL: 18.3+/-28.2mg/dl 95% CI:
      10.2 to 26.3), CVR: 6.7+/-7.7% (95% CI: 4.5 to 8.9), PE: 3.9+/-10.2 ? (95% CI:
      0.9 to 6.8), and an increase in SHS; 4.7+/-5.7 (95% CI: 3 to 6.3). CONCLUSIONS:
      In diabetics over 65 years, a program of monitored aerobic exercise, of easy
      implementation, improves HbA1c, BP, cholesterol, CVR, PE, and SHS.

PMID- 25769196
TI  - Lateral versus posterior approach for insertion of hemiarthroplasties for hip
      fractures: A randomised trial of 216 patients.
AB  - Continued debate exists about the merits of the different surgical approaches for
      arthroplasty of the hip. For hemiarthroplasty to the hip the two most commonly
      used approaches are lateral and posterior. 216 patients with an intracapsular hip
      fracture being treated with a cemented hemiarthroplasty were randomised to
      surgery using either a lateral or posterior approach. Surviving patients were
      followed up for one year with pain and functional outcomes assessed by an
      assessor blinded to the treatment allocation. No statistically significant
      differences were observed for any of the outcome measures including mortality,
      degree of residual pain and regain of walking ability. A subjective assessment of
      the ease of surgery favoured the lateral approach. In conclusion both surgical
      approaches appear to produce comparable function outcomes. 

PMID- 25769197
TI  - High-grade renal injuries are often isolated in sports-related trauma.
AB  - INTRODUCTION: Most high-grade renal injuries (American Association for Surgery of
      Trauma (AAST) grades III-V) result from motor vehicle collisions associated with
      numerous concomitant injuries. Sports-related blunt renal injury tends to have a
      different mechanism, a solitary blow to the flank. We hypothesized that high
      grade renal injury is often isolated in sports-related renal trauma. MATERIAL AND
      METHODS: We identified patients with AAST grades III-V blunt renal injuries from
      four level 1 trauma centres across the United States between 1/2005 and 1/2014.
      Patients were divided into "Sport" or "Non-sport" related groups. Outcomes
      included rates of hypotension (systolic blood pressure <90mm Hg), tachycardia
      (>110bpm), concomitant abdominal injury, and procedural/surgical intervention
      between sports and non-sports related injury. RESULTS: 320 patients met study
      criteria. 18% (59) were sports-related injuries with the most common mechanisms
      being skiing, snowboarding and contact sports (25%, 25%, and 24%, respectively).
      Median age was 24 years for sports and 30 years for non-sports related renal
      injuries (p=0.049). Males were more commonly involved in sports related injuries
      (85% vs. 72%, p=0.011). Median injury severity score was lower for sports related
      injuries (10 vs. 27, p<0.001). There was no difference in renal abbreviated
      injury scale scores. Sports related trauma was more likely to be isolated without
      other significant injury (69% vs. 39% (p<0.001)). Haemodynamic instability was
      present in 40% and 51% of sports and non-sports renal injuries (p=0.30). Sports
      injuries had lower transfusion (7% vs. 47%, p<0.001) and lower mortality rates
      (0% vs. 6%, p=0.004). There was no difference in renal-specific procedural
      interventions between the two groups (17% sports vs. 18% non-sports, p=0.95).
      CONCLUSIONS: High-grade sports-related blunt renal trauma is more likely to occur
      in isolation without other abdominal or thoracic injuries and clinicians must
      have a high suspicion of renal injury with significant blows to the flank during
      sports activities.

PMID- 25769198
TI  - Use of antidepressant medication after road traffic injury.
AB  - OBJECTIVES: Mental ill health after road traffic injury is common, as is the use
      of antidepressant medication after injury. Little is known about antidepressant
      use by injured people prior to their injury. The aim of this study is to describe
      the nature and extent of antidepressant use before and after road traffic injury.
      METHODS: Victorian residents who claimed Transport Accident Commission (TAC)
      compensation for a non-catastrophic injury that occurred between 2010 and 2012
      and provided consent for Pharmaceutical Benefits Scheme (PBS) linkage were
      included (n=734). PBS records dating from 12 months prior through to 12 months
      post injury were provided by the Department of Human Services (Canberra). PBS and
      TAC claims data were linked. RESULTS: Among participants, 12% used
      antidepressants before injury (84.4D efined Daily Doses/1000 person-days) and 17%
      used antidepressants after injury (114.1DDD/1000p-d). Only 7.7% of the injured
      cohort commenced antidepressant treatment post injury. Thus, of all post-injury
      antidepressant use, 45% could potentially be related to the incident injury, with
      the remaining 55% most probably a continuation of pre-injury use. Pre-injury use
      was more common among women (109.4 vs. 54.6 DDD/1000p-d, p<0.0001), and those
      with whiplash injury (119.3 vs. 73.1, p=0.03). Cyclists and motorcyclists were
      less likely to use antidepressants pre-injury than car drivers (18.3 vs. 16.9 vs.
      109.3, respectively; p<0.001). CONCLUSIONS: Less than half of post-injury
      antidepressant use could potentially be attributable to the incident injury.
      These results highlight the importance of obtaining information on pre-injury
      health status before interpreting post-injury health service use to be an outcome
      of the injury in question.

PMID- 25769200
TI  - Isolated hip fracture care in an inclusive trauma system: A trauma system wide
      evaluation.
AB  - INTRODUCTION: Elderly patients with a hip fracture represent a large proportion
      of the trauma population; however, little is known about outcome differences
      between different levels of trauma care for these patients. The aim of this study
      is to analyse the outcome of trauma care in patients with a hip fracture within
      our inclusive trauma system. MATERIALS AND METHODS: Retrospective cohort study.
      Data were collected from the electronic patient documentation of patients, with
      an isolated hip fracture (aged >= 60), admitted to a level I or level II trauma
      centre between January 2008 and December 2012. Main outcomes were time to
      operative treatment, complications, mortality, and secondary surgical
      intervention rate. RESULTS: A total of 204 (level I) and 1425 (level II) patients
      were admitted. Significantly more ASA4 patients, by the American Society of
      Anesthesiologists (ASA) classification, were treated at the level I trauma
      centre. At the level II trauma centre, median time to surgical treatment was
      shorter (0 days; IQR 0-1 vs 1 day; IQR 1-2; P < 0.001), which was mainly
      influenced by postponement due to lack of operation room availability (14%, n =
      28) and co-morbidities (13%, n = 26) present at the level I trauma centre. At the
      level II trauma centre, hospital stay was shorter (9 vs 11 days; P < 0.001) and
      the complication rate was lower (41%; n = 590 vs 53%; n = 108; P = 0.002), as was
      mortality (4%; n = 54 vs 7%; n = 15; P = 0.018). Secondary surgical intervention
      was performed less often at the level II trauma centre (6%; n = 91 vs 12%; n =
      24; P = 0.005). However, no differences in secondary surgical procedures due to
      inadequate postoperative outcome or implant failure were observed. CONCLUSION AND
      RELEVANCE: The clinical pathway and the large volume of patients at the level II
      centre resulted in earlier surgical intervention, lower overall complication and
      mortality rate, and a shorter length of stay. Therefore, the elderly patient with
      a hip fracture should ideally be treated in the large-volume level II hospital
      with a pre-established clinical pathway. However, complex patients requiring
      specific care that can only be provided at the level I trauma centre may be
      treated there with similar operative results.

PMID- 25769199
TI  - Which pelvic ring fractures are potentially lethal?
AB  - PURPOSE: Global mortality of polytraumatised patients presenting pelvic ring
      fractures remains high (330%), despite improvements in treatment algorithms in
      Level I Trauma Centers. Many classifications have been developed in order to
      identify and analyse these pelvic ring lesions. However, it remains difficult to
      predict intra-pelvic haemorrhage. The aim of this study was to identify pelvic
      ring anatomical lesions associated with significant blood loss, susceptible to
      lead to life-threatening haemorrhage. MATERIAL AND METHOD: This study focused on
      a retrospective analysis of patients' medical files, all of whom were admitted to
      one of the shock rooms of Grenoble University Hospital, France, between January
      2004 and December 2008. Treatment was given according to the institutional
      algorithm of the Alps Trauma Center and Emergency North Alpine Network Trauma
      System (TRENAU). Different hemodynamical parameters at arrival were measured, and
      the fractures were classified according to Young and Burgess, Tile, Letournel and
      Denis. One hundred and ninety seven patients were analysed. They were subdivided
      into two groups, embolised (Group E) and non-embolised (Group NE). RESULTS: Group
      NE included 171 patients with a mean age of 40.2 +/- 8.7 years (15-90). Group E
      included 26 patients with a mean age of 41.6 +/- 5.3 years (18-67). Twenty-six
      patients died during the initial treatment phase. Eleven belonged to Group E and
      15 to Group NE. Mortality was significantly higher in Group E (42.3% vs 8.8% in
      Group NE) (p < 0.05). There were significantly many more Tile C unstable
      fractures in Group E (p = 0.0014), and anterior lesions, according to Letournel,
      with pubic symphysis disruption were significantly more likely to lead to active
      bleeding treated by selective embolisation (p = 0.0014). Posterior pelvic ring
      lesions with iliac wing fracture and transforaminal sacral fractures (Denis 2)
      were also more frequently associated with bleeding treated by embolisation (p =
      0.0088 and p = 0.0369 respectively). DISCUSSION/CONCLUSION: It appears that in
      our series the primary identification and classification of osteo-ligamentous
      lesions (according to Letournel and Denis' classifications) allows to anticipate
      the importance of bleeding and to adapt the management of patients accordingly,
      in order to quickly organise angiography with embolisation.

PMID- 25769201
TI  - A prospective randomised study comparing TightRope and syndesmotic screw fixation
      for accuracy and maintenance of syndesmotic reduction assessed with bilateral
      computed tomography.
AB  - BACKGROUND: The accuracy and maintenance of syndesmosis reduction are essential
      when treating ankle fractures with accompanying syndesmosis injuries. The primary
      aim of this study was to compare syndesmosis screw and TightRope fixation in
      terms of accuracy and maintenance of syndesmosis reduction using bilateral
      computed tomography (CT). STUDY DESIGN: Single centre, prospective randomised
      controlled clinical trial; Level of evidence 1. METHODS: This study
      (ClinicalTrials.gov, NCT01742650) compared fixation with TightRope((r)) (Arthrex,
      Naples, FL, USA) or with one 3.5-mm tricortical trans-syndesmotic screw in terms
      of accuracy and maintenance of syndesmosis reduction in Lauge-Hansen pronation
      external rotation, Weber C-type ankle fractures with associated syndesmosis
      injury. Twenty-one patients were randomised to TightRope fixation and 22 to
      syndesmotic screw fixation. Syndesmosis reduction was assessed using bilateral CT
      intraoperatively or postoperatively, and also at least 2 years after surgery.
      Functional outcomes and quality of life were assessed using the Olerud-Molander
      score, a 100-mm Visual Analogue Scale, the Foot and Ankle Outcome Score, and the
      RAND 36-Item Health Survey. Grade of osteoarthritis was qualified with follow-up
      cone-beam CT. RESULTS: According to surgeons' assessment from intraoperative CT,
      screw fixation resulted in syndesmosis malreduction in one case whereas seven
      syndesmosis were considered malreduced when TightRope was used. However, open
      exploration and postoperative CT of these seven cases revealed that syndesmosis
      was well reduced if the ankle was supported at 90. Retrospective analysis of the
      intra- and post-operative CT by a radiologist showed that one patient in each
      group had incongruent syndesmosis. Follow-up CT identified three patients with
      malreduced syndesmosis in the syndesmotic screw fixation group, whereas
      malreduction was seen in one patient in the TightRope group (P = 0.33).
      Functional scores and the incidence of osteoarthritis showed no significant
      difference between groups. CONCLUSION: Syndesmotic screw and TightRope had
      similar postoperative malreduction rates. However, intraoperative CT scanning of
      ankles with TightRope fixation was misleading due to dynamic nature of the
      fixation. After at least 2 years of follow-up, malreduction rates may slightly
      increase when using trans-syndesmotic screw fixation, but reduction was well
      maintained when fixed with TightRope. Neither the incidence of ankle joint
      osteoarthritis nor functional outcome significantly differed between the fixation
      methods.

PMID- 25769202
TI  - Titanium mesh as a low-profile alternative for tension-band augmentation in
      patella fracture fixation: A biomechanical study.
AB  - OBJECTIVES: We performed a simple biomechanical study to compare the fixation
      strength of titanium mesh with traditional tension-band augmentation, which is a
      standard treatment for transverse patella fractures. We hypothesised that
      titanium mesh augmentation is not inferior in fixation strength to the standard
      treatment. METHODS: Twenty-four synthetic patellae were tested. Twelve were fixed
      with stainless steel wire and parallel cannulated screws. Twelve were fixed with
      parallel cannulated screws, augmented with anterior titanium mesh and four
      screws. A custom test fixture was developed to simulate a knee flexed to 90
      degrees . A uniaxial force was applied to the simulated extensor mechanism at
      this angle. A non-inferiority study design was used to evaluate ultimate force
      required for failure of each construct as a measure of fixation strength.
      Stiffness of the bone/implant construct, fracture gap immediately prior to
      failure, and modes of failure are also reported. RESULTS: The mean difference in
      force at failure was -23.0 N (95% CI: -123.6 to 77.6N) between mesh and wire
      constructs, well within the pre-defined non-inferiority margin of -260 N. Mean
      stiffness of the mesh and wire constructs were 19.42 N/mm (95% CI: 18.57-20.27
      N/mm) and 19.49 N/mm (95% CI: 18.64-20.35 N/mm), respectively. Mean gap distance
      for the mesh constructs immediately prior to failure was 2.11 mm (95% CI: 1.35
      2.88 mm) and 3.87 mm (95% CI: 2.60-5.13 mm) for wire constructs. CONCLUSIONS:
      Titanium mesh augmentation is not inferior to tension-band wire augmentation when
      comparing ultimate force required for failure in this simplified biomechanical
      model. Results also indicate that stiffness of the two constructs is similar but
      that the mesh maintains a smaller fracture gap prior to failure. The results of
      this study indicate that the use of titanium mesh plating augmentation as a low
      profile alternative to tension-band wiring for fixation of transverse patella
      fractures warrants further investigation.

PMID- 25769203
TI  - Fetal heart rate monitoring.
AB  - Electronic fetal heart rate monitoring is a widely utilized means of assessment
      of fetal status during labor. Whereas little evidence exists regarding efficacy,
      this modality continues to be used extensively in every modern labor and delivery
      unit in developed countries. It is of importance that all providers of health
      care to the woman in labor and her newborn have a clear understanding of the
      basic pathophysiology of fetal heart rate monitoring and an appreciation for
      labor course and concerns as they arise in order to optimize outcomes and patient
      safety. 

PMID- 25769204
TI  - Nasopharyngeal carcinoma: a review.
AB  - Nasopharyngeal carcinoma is an umbrella term for a group of malignant epithelial
      tumors with different etiopathogenesis and a broad range of histopathological
      appearances. Some types have a dramatically skewed geographical and ethnic
      distribution and shows virtually 100% association with Epstein Barr virus. The
      field of other/contributing etiological factors are only partially known and
      recently a subset of this carcinoma has been linked to transcriptionally active
      Human Papilloma virus. As with all malignant tumors, the clinical stage of
      disease is of paramount importance. Despite loco-regionally advanced disease, a
      large proportion of these patients respond well to radiotherapy, either alone or
      in combination with chemotherapy and long term sequelae including, but not
      limited to, development of secondary, radiation-induced malignant tumors is a
      real clinical problem. This review attempts to provide the practicing pathologist
      with an overview of nasopharyngeal carcinoma and recent advances in the
      multifaceted understanding of this group of neoplasms. In addition, some
      information on prognosis, staging, treatment and treatment related complications
      in this group of patients is provided. 

PMID- 25769205
TI  - Issues and challenges associated with classifying neoplasms in percutaneous
      needle biopsies of incidentally found small renal masses.
AB  - Percutaneous needle core biopsy has become acceptable for classifying renal
      tumours and guiding patient management in the setting of an incidentally-detected
      small renal mass (SRM), defined as an asymptomatic, non-palpable mass <4cm in
      maximum dimension. Long-held concerns preventing the incorporation of biopsies
      into routine patient care, including the perception of poor diagnostic yield and
      risks of complications such as bleeding or biopsy tract seeding, have largely
      been disproven. While needle biopsies for SRMs have traditionally been performed
      in academic centres, pathologists based in non-academic centres can expect to
      encounter these specimens as urologists and/or interventional radiologist
      trainees complete their training programs and begin work in non-academic centres.
      This review covers the rationale for performing these biopsies, the expected
      diagnostic yield, relevant differential diagnoses and an approach to classifying
      SRMs based on limited samples as well as the use of immunohistochemical (IHC)
      staining panels to aid in this process. There is also an undeniable learning
      curve for pathologists faced with reporting these biopsies and a number of issues
      and potential pitfalls attributable to sampling must be kept in mind by
      pathologists and clinicians alike. 

PMID- 25769206
TI  - Immunohistochemical markers in lymphoid malignancies: Protein correlates of
      molecular alterations.
AB  - Histomorphology, immunohistochemistry (IHC), and genetics are essential tools for
      the evaluation and classification of lymphoid malignancies. Advances in
      diagnostic techniques include the development of immunohistochemical assays that
      can serve as surrogates for genetic tests. We review the performance of a select
      subset of assays that detect the aberrant expression of onco-proteins secondary
      to chromosomal translocations (MYC; BCL2), somatic mutations (BRAF V600E;
      NOTCH1), and gene copy number gains (CD274 (encoding PD-L1); PDCD1LG2 (encoding
      PD-L2)) in fixed tissue biopsy sections. We discuss the limitations of IHC, but
      also its primary advantage over genetics; specifically, its ability to assess the
      final, common phenotypic consequences of a multitude of genetic and non-genetic
      events that influence protein expression. The information provided by IHC and
      genetic testing are thus intimately related; surgical pathologists will
      increasingly need to interpret and integrate the results of both to provide a
      comprehensive assessment of tumor biology and guide therapy. 

PMID- 25769207
TI  - Accelerating measles elimination and strengthening routine immunization services
      in Guizhou Province, China, 2003-2009.
AB  - BACKGROUND: To develop a successful model for accelerating measles elimination in
      poor areas of China, we initiated a seven-year project in Guizhou, one of the
      poorest provinces, with reported highest measles incidence of 360 per million
      population in 2002. METHODS: Project strategies consisted of strengthening
      routine immunization services, enforcement of school entry immunization
      requirements at kindergarten and school, conducting supplemental measles
      immunization activities (SIAs), and enhancing measles surveillance. We measured
      coverage of measles containing vaccines (MCV) by administrative reporting and
      population-based sample surveys, systematic random sampling surveys, and
      convenience sampling surveys for routine immunization services, school entry
      immunization, and SIAs respectively. We measured impact using surveillance based
      measles incidence. RESULTS: Routine immunization coverage of the 1st dose of MCV
      (MCV1) increased from 82% to 93%, while 2nd dose of MCV (MCV2) coverage increased
      from 78% to 91%. Enforcement of school entry immunization requirements led to an
      increase in MCV2 coverage from 36% on primary school entry in 2004 to 93% in
      2009. Province-wide SIAs achieved coverage greater than 90%. The reported annual
      incidence of measles dropped from 200 to 300 per million in 2003 to 6 per million
      in 2009, and sustained at 0.9-2.2 per million in 2010-2013. CONCLUSIONS: This
      project found that a package of strategies including periodic SIAs, strengthened
      routine immunization, and enforcing school entry immunization requirements, was
      an effective approach toward achieving and sustaining measles elimination in less
      developed area of China.

PMID- 25769208
TI  - Report of the 2014 Cent Gardes HIV Vaccine Conference - Part 1: Neutralizing
      Antibodies; Fondation Merieux Conference Center, Veyrier du Lac, France, 5-7
      October 2014.
AB  - The 2014 Cent Gardes Conference took place on October 5-7 at the Fondation
      Merieux Conference Center, on the shores of the Annecy Lake. The aim of the
      meeting was to review progress in the field of HIV vaccines during the last two
      years and to explore the promising avenues of future research. The identification
      of broadly neutralizing antibodies (bNAbs) able to neutralize a majority of
      circulating HIV strains has encouraged hopes for a highly effective "universal"
      HIV vaccine. Analysis of B-cell maturation that leads to the production of bNAbs,
      however, appears extremely complex, and not easily reproduced by classical active
      immunization. The use of bNAbs for passive immunization is thus being explored as
      an alternative, either for immunotherapy or prophylaxis. Their delivery by a
      recombinant adenovirus-associated virus (AAV), also known as vector
      immunoprophylaxis, has demonstrated proof-of-concept in animal models and is now
      in early stage clinical trials. Other approaches were discussed at the meeting,
      such as eliciting long-lasting T cell or mucosal immunity. In spite of remarkable
      progress, the quest for an efficacious HIV vaccine remains a daunting challenge. 

PMID- 25769209
TI  - Vaccine introduction in the Democratic People's Republic of Korea.
AB  - The feasibility of mass vaccination campaigns for Japanese encephalitis and
      Haemophilus influenzae type b infections was explored in the Democratic People's
      Republic of Korea using pilot vaccination studies. The experiences from these
      initial studies were then used to support larger vaccination campaigns in
      children at risk of these infections. We discuss the challenges and requirements
      for the inclusion of additional vaccines into the existing expanded program on
      immunization in the country. 

PMID- 25769210
TI  - Newcastle disease virus outbreaks in India: Time to revisit the vaccine type and
      strategies.

PMID- 25769211
TI  - Percutaneous hepatic and renal biopsy procedures: an 18-year analysis of changing
      utilization, specialty roles, and sites of service.
AB  - PURPOSE: To evaluate national trends in percutaneous hepatic and renal biopsy
      procedures with regard to utilization, specialty group roles, and sites of
      service. MATERIALS AND METHODS: Service-specific claims data for percutaneous
      hepatic and renal biopsy procedures were identified using Medicare Physician
      Supplier Procedure Summary Master Files for the period 1994-2012. Longitudinal
      national utilization rates were calculated using annual Medicare enrollment data.
      Procedure volumes by specialty group and site of service were analyzed. RESULTS:
      Between 1994 and 2012, the number of hepatic and renal biopsies performed on
      Medicare Part B beneficiaries increased 22% (from 43,478 to 53,055) and 68%
      (19,508 to 32,762), respectively. Per 100,000 beneficiaries, the utilization of
      hepatic and renal biopsy increased 19.6% (from 134.6 to 161.0) and 69.3% (from
      60.4 to 102.2). Procedures performed by radiologists disproportionately increased
      81% (from 25,484 to 46,181) and 236% (from 6,855 to 23,003), respectively.
      Although utilization in the inpatient setting declined 28.7% (from 68.2 to 48.6
      per 100,000) for hepatic biopsies and 9.4% (from 43.1 to 39.1) for renal
      biopsies, there were larger concurrent increases of 73.9% (from 59.2 to 103.0)
      and 303.9% (from 15.1 to 61.0) in utilization in the outpatient setting.
      CONCLUSIONS: Between 1994 and 2012, national utilization of percutaneous hepatic
      and renal biopsy procedures in the Medicare population increased as services
      increasingly shifted from the hospital inpatient to outpatient setting.
      Radiologists are presently and increasingly the dominant providers of both
      services.

PMID- 25769213
TI  - R.E.N.A.L. (Radius, exophytic/endophytic, nearness to collecting system or sinus,
      anterior/posterior, and location relative to polar lines) nephrometry score
      predicts early tumor recurrence and complications after percutaneous ablative
      therapies for renal cell carcinoma: a 5-year experience.
AB  - PURPOSE: To investigate the prognostic value of R.E.N.A.L. (radius,
      exophytic/endophytic, nearness to collecting system or sinus, anterior/posterior,
      and location relative to polar lines) nephrometry score after percutaneous
      ablation of renal cell carcinoma (RCC). MATERIALS AND METHODS: A retrospective 5
      year study was performed. Participants were 87 consecutive patients (median age,
      67.1 y; 59.7% male, 40.3% female) with 101 biopsy-proven RCCs who underwent
      percutaneous ablation (54.0% cryoablation, 46.0% radiofrequency ablation). Follow
      up computed tomography or magnetic resonance imaging was performed in all cases
      (mean follow-up, 34.6 mo +/- 23.5). R.E.N.A.L. scores were analyzed to determine
      the association of the score with treatment outcomes and complications. RESULTS:
      All tumors corresponded to stage 1A disease. Mean tumor size was 2.05 cm (range,
      0.7-3.9 cm), and 50.5% of the lesions measured > 2 cm. Nephrometry score was > 8
      in 31.4% of lesions. Overall recurrence rate was 16.8%, first-year recurrence
      rate was 7.9%, and complication rate was 9.9%. A nephrometry score > 8 was
      associated with increased complications after percutaneous ablation (P < .0001),
      increased overall recurrence (P < .0001), and increased risk of first-year
      recurrence (P < .0001). Immediate complications were associated with tumor size >
      2 cm (P < .0001) and risk of local recurrence (P < .001). Age, gender, and
      percutaneous ablation technique were not correlated with recurrence or immediate
      complications. Patients undergoing cryoablation had a higher nephrometry score
      with no significant differences in recurrence rate compared with RF ablation (P =
      .199). CONCLUSIONS: A R.E.N.A.L. nephrometry score >= 8 predicts recurrence and
      complications after percutaneous renal ablation.

PMID- 25769214
TI  - Traumatic Carotid Esophageal Fistula.

PMID- 25769212
TI  - Feasibility of catheter-directed intraluminal irreversible electroporation of
      porcine ureter and acute outcomes in response to increasing energy delivery.
AB  - PURPOSE: To evaluate the feasibility of focal intraluminal irreversible
      electroporation (IRE) in the ureter with a novel electrode catheter and to study
      the treatment effects in response to increasing pulse strength. MATERIALS AND
      METHODS: Five IRE treatment settings were each evaluated twice for the ablation
      of normal ureter in 5 Yorkshire pigs (n = 1-4 ablations per animal; total of 10
      ablations) with the use of a prototype device under ultrasound and fluoroscopic
      guidance. Animals received unilateral or bilateral treatment, limited to a
      maximum of 2 ablations in any 1 ureter. Treatment was delivered with increasing
      pulse strength (from 1,000 V to 3,000 V in increments of 500 V) while keeping the
      pulse duration (100 MUs) and number of pulses (n = 90) constant. Ureter patency
      was assessed with antegrade ureteropyelography immediately following treatment.
      Animals were euthanized within 4 hours after treatment, and treated urinary tract
      was harvested for histopathologic analysis with hematoxylin and eosin and Masson
      trichrome stains. RESULTS: IRE was successfully performed in all animals, without
      evidence of ureteral perforation. Hematoxylin and eosin analysis of IRE
      treatments demonstrated full-thickness ablation at higher field strengths (mucosa
      to the adventitia). Masson trichrome stains showed preservation of connective
      tissue at all field strengths. CONCLUSIONS: Intraluminal catheter-directed IRE
      ablation is feasible and produces full-thickness ablation of normal ureters.
      There was no evidence of lumen perforation even at the maximum voltages
      evaluated.

PMID- 25769215
TI  - The Revista de Gastroenterologia de Mexico: continuity or renewal?

PMID- 25769216
TI  - [Second European evidence-based consensus on the diagnosis and management of
      ulcerative colitis Part 3: Special situations (Spanish version)].

PMID- 25769218
TI  - Development of an innovative device for ultrasonic elliptical vibration cutting.
AB  - An innovative ultrasonic elliptical vibration cutting (UEVC) device with 1st
      resonant mode of longitudinal vibration and 3rd resonant mode of bending
      vibration was proposed in this paper, which can deliver higher output power
      compared to previous UEVC devices. Using finite element method (FEM), resonance
      frequencies of the longitudinal and bending vibrations were tuned to be as close
      as possible in order to excite these two vibrations using two-phase driving
      voltages at a single frequency, while wave nodes of the longitudinal and bending
      vibrations were also adjusted to be as coincident as possible for mounting the
      device at a single fixed point. Based on the simulation analysis results a
      prototype device was fabricated, then its vibration characteristics were
      evaluated by an impedance analyzer and a laser displacement sensor. With two
      phase sinusoidal driving voltages both of 480 V(p-p) at an ultrasonic frequency
      of 20.1 kHz, the developed prototype device achieved an elliptical vibration with
      a longitudinal amplitude of 8.9 MUm and a bending amplitude of 11.3 MUm. The
      performance of the developed UEVC device is assessed by the cutting tests of
      hardened steel using single crystal diamond tools. Experimental results indicate
      that compared to ordinary cutting process, the tool wear is reduced significantly
      by using the proposed device.

PMID- 25769217
TI  - [Second European evidence-based consensus on the diagnosis and management of
      ulcerative colitis Part 2: Current management (Spanish version)].

PMID- 25769219
TI  - Ultrasonic pulse velocity for the evaluation of physical and mechanical
      properties of a highly porous building limestone.
AB  - UPV as non-destructive technique can effectively contribute to the low invasive
      in situ analysis and diagnosis of masonry elements related to the conservation,
      rehabilitation and strengthening of the built heritage. The use of non
      destructive and non-invasive techniques brings all the times many advantages in
      diagnostic activities on pre-existing buildings in terms of sustainability;
      moreover, it is a strong necessity with respect to the conservation constraints
      when dealing with the historical-architectural heritage. In this work laboratory
      experiments were carried out to investigate the effectiveness of ultrasonic pulse
      velocity (UPV) in evaluating physical and mechanical properties of Lecce stone, a
      soft and porous building limestone. UPV and selected physical-mechanical
      parameters such as density and uniaxial compressive strength (UCS) were
      determined. Factors such as anisotropy and water presence that induce variations
      on the ultrasonic velocity were also assessed. Correlations between the analysed
      parameters are presented and discussed. The presence of water greatly affected
      the values of the analysed parameters, leading to a decrease of UPV and to a
      strong reduction of the compressive strength. A discussion of the role of the
      water on these results is provided. Regression analysis showed a reliable linear
      correlation between UPV and compressive strength, which allows a reasonable
      estimation of the strength of Lecce stone by means of non-destructive testing
      methods such as the ultrasonic wave velocity. Low correlation between UPV and
      density was found, suggesting that other factors than density, related to the
      fabric and composition, also influence the response of the selected stone to the
      UPV. They have no influence on the UCS, that instead showed to be highly
      correlated with the packing density. 

PMID- 25769220
TI  - Obstructive sleep apnoea in craniofacial microsomia: a systematic review.
AB  - Children with craniofacial microsomia (CFM) are at risk of obstructive sleep
      apnoea (OSA). This systematic review provides an overview of the literature on
      the prevalence of OSA in children with CFM. A search was performed in PubMed,
      Embase, Cochrane Library, and Web of Science for articles on CFM and OSA. The
      following data were extracted from the articles: number of patients, patient
      characteristics, presence of OSA, polysomnography outcomes, and the treatments
      and outcomes of OSA. We included 16 articles on CFM and OSA, four of which
      reported the prevalence of OSA (range 7-67%). Surgical treatment was more often
      described in these patients than conservative treatment. According to the
      literature, OSA is related to CFM. However, as there have been no prospective
      studies and few studies have presented objective measurements, no definitive
      conclusions can be drawn. Prospective studies are needed to determine the
      prevalence of OSA in patients with CFM. 

PMID- 25769221
TI  - Sequential delivery of BMP-2 and BMP-7 for bone regeneration using a heparinized
      collagen membrane.
AB  - To investigate the effect of the sequential delivery of bone morphogenetic
      proteins BMP-2 and BMP-7 on bone regeneration in rat calvarial defects (40
      Sprague-Dawley rats, 8mm defect size), all animals were treated with a
      hydroxyapatite (HA)/tricalcium phosphate (TCP) bone graft covered with a collagen
      membrane. The experimental groups were as follows: (1) control group: unmodified
      collagen (no treatment); (2) BMP-2 group: 5 MUg of BMP-2; (3) hep-BMP-7 group: 5
      MUg BMP-7 chemically bound to heparinized collagen; and (4) BMP-2/hep-BMP-7
      group: 2.5 MUg BMP-7 bound to heparinized collagen and subsequently treated with
      2.5 MUg BMP-2. Defect healing was examined at 2 and 8 weeks after surgery. The
      BMP-2 group showed the largest new bone area at week 2 (29.3 +/- 7.3%; P =
      0.009); new bone areas in the hep-BMP-7 and BMP-2/hep-BMP-7 groups were similar
      (11.8 +/- 3.4% and 12.9 +/- 5.71%, respectively; P = 0.917). After 8 weeks, the
      BMP-2/hep-BMP-7 group showed the largest new bone area (43.3 +/- 6.2%), followed
      by the BMP-2 and hep-BMP-7 groups (P = 0.013). Accordingly, in comparison with
      single deliveries of BMP-2 and BMP-7, sequential delivery of BMP-2 and BMP-7
      using a heparinized collagen membrane significantly induced new bone formation
      with a smaller quantity of BMP-2 in rat calvarial defects.

PMID- 25769222
TI  - Conditional survival estimates for childhood cancer in Australia, 2002-2011: A
      population-based study.
AB  - BACKGROUND: Conditional survival estimates take into account the time that a
      patient has remained alive following diagnosis to provide a realistic perspective
      on the probability of longer term survival. Such estimates are scarce for
      childhood cancer, particularly by age at diagnosis or stage of cancer. METHODS:
      De-identified population-based data were obtained from the Australian Paediatric
      Cancer Registry for children aged 0-14 years diagnosed with cancer between 1983
      and 2010. Mortality status was followed up to the end of 2011. The hybrid period
      method was used to calculate relative survival estimates for those who were at
      risk during the period 2002-2011. Conditional survival stratified by diagnostic
      group or subgroup, age and stage at diagnosis was then obtained from the ratio of
      the relative survival estimates at different time points. RESULTS: A total of
      13,537 children were eligible for inclusion. Five-year survival for all childhood
      cancers combined improved from 82% at diagnosis (95% confidence interval=81-83%)
      to 89% (88-90%) conditional on surviving one year, and 97% (97-98%) conditional
      on surviving five years after diagnosis. Conditional survival reached 95% within
      five years of diagnosis for nearly all types of cancer, regardless of a child's
      age or stage at diagnosis. CONCLUSION: Most children diagnosed with cancer who
      are alive five years after diagnosis can anticipate similar survival to children
      in the general population. This information may help alleviate some of the
      distress associated with childhood cancer, particularly for those with an
      initially poor prognosis.

PMID- 25769223
TI  - Risk of oesophageal cancer among patients previously hospitalised with eating
      disorder.
AB  - BACKGROUND: It has been suggested that the risk of oesophageal adenocarcinoma
      might be increased in patients with a history of eating disorders due to acidic
      damage to oesophageal mucosa caused by self-induced vomiting practiced as a
      method of weight control. Eating disorders have also been associated with risk
      factors for squamous cell carcinoma of the oesophagus, including alcohol use
      disorders, as well as smoking and nutritional deficiencies, which have been
      associated with both main sub-types of oesophageal cancer. There have been
      several case reports of oesophageal cancer (both main sub-types) arising in
      patients with a history of eating disorders. METHODS: We used linked records of
      hospitalisation, cancer registration and mortality in Scotland spanning 1981-2012
      to investigate the risk of oesophageal cancer among patients with a prior history
      of hospitalisation with eating disorder. The cohort was restricted to patients
      aged >=10 years and <60 years at the date of first admission with eating
      disorder. Disregarding the first year of follow-up, we calculated indirectly
      standardised incidence ratios using the general population as the reference group
      to generate expected numbers of cases (based on age-, sex-, socio-economic
      deprivation category-, and calendar period-specific rates of disease). RESULTS:
      After exclusions, the cohort consisted of 3617 individuals contributing 52,455
      person-years at risk. The median duration of follow-up was 13.9 years. Seven
      oesophageal cancers were identified, as compared with 1.14 expected, yielding a
      standardised incidence ratio of 6.1 (95% confidence interval: 2.5-12.6). All were
      squamous cell carcinomas arising in females with a prior history of anorexia
      nervosa. CONCLUSIONS: Patients hospitalised previously with eating disorders are
      at increased risk of developing oesophageal cancer. Confounding by established
      risk factors (alcohol, smoking, and nutritional deficiency) seems a more likely
      explanation than acidic damage through self-induced vomiting because none of the
      incident cases of oesophageal cancer were adenocarcinomas, and because the study
      cohort had higher than background rates of hospitalisation with alcohol-related
      conditions and chronic obstructive pulmonary disease.

PMID- 25769224
TI  - Unobtrusive monitoring and identification of fall accidents.
AB  - Falls are a societal and economic problem of great concern with large parts of
      the population, in particular older citizens, at significant risk and the result
      of a fall often being grave. It has long been established that it is of
      importance to provide help to a faller soon after the event to prevent
      complications and this can be achieved with a fall monitor. Yet, the practical
      use of currently available fall monitoring solutions is limited due to accuracy,
      usability, cost, and, not in the least, the stigmatising effect of many
      solutions. This paper proposes a fall sensor concept that can be embedded in the
      user's footwear and discusses algorithms, software and hardware developed. Sensor
      performance is illustrated using results of a series of functional tests. These
      show that the developed sensor can be used for the accurate measurement of
      various mobility and gait parameters and that falls are detected accurately. 

PMID- 25769225
TI  - Age-dependent vulnerability of cyclosporine-associated encephalopathy in
      children.
AB  - INTRODUCTION: Cyclosporine (CsA) is an immunosuppressant known for its
      neurotoxicity, which presents with acute encephalopathy and seizures in the most
      severe form. However, whether there is age-related neurological susceptibility in
      pediatric population is poorly defined. The study aims to examine the
      vulnerability of CsA neurotoxicity among different age groups of pediatric
      patients in terms of occurrence rate, acute presentations, long-term outcomes,
      and neuroimaging findings. METHODS: Pediatric patients (age <18 years) who
      received CsA in a tertiary referral center between July 1, 1988 and August 31,
      2011 were retrospectively reviewed for CsA-related encephalopathy. The clinical
      presentations, demographic data, and laboratory examinations were analyzed
      through t-test for numerical and Fisher's exact test for categorical variables.
      Exact logistic regression was used to examine the effect of each variables.
      RESULTS: Twelve (8%) of the enrolled 146 patients developed CsA-induced
      encephalopathy. Compared to the non-neurotoxicity group, the neurotoxicity group
      was significantly younger upon starting CsA (p = 0.008) and had higher
      percentages of hypertension after CsA treatment (p = 0.01). Regression analysis
      showed that age <6 years (OR 7.6, 95% CI 1.6-51.5; p = 0.007) and hypertension
      after CsA (OR 6.3, 95% CI 1.4-35.4; p = 0.016) were significantly associated with
      CsA encephalopathy. Younger children were prone to have more severe seizures in
      the acute stage and more epilepsy and neuropsychiatric disorders in the future.
      Follow-up neuroimaging showed parietal cerebral atrophy in all examined children
      <6 years of age. CONCLUSIONS: Age-dependent susceptibility of CsA neurotoxicity
      occurs in children, with severe acute presentations and long-term sequelae in
      children below 6 years old.

PMID- 25769227
TI  - Mathematics toward systems biology and complexity: reply to comments on "On the
      interplay between mathematics and biology - hallmarks toward a new systems
      biology".

PMID- 25769226
TI  - 4p16.1-p15.31 duplication and 4p terminal deletion in a 3-years old Chinese girl:
      Array-CGH, genotype-phenotype and neurological characterization.
AB  - BACKGROUND: Microscopically chromosome rearrangements of the short arm of
      chromosome 4 include the two known clinical entities: partial trisomy 4p and
      deletions of the Wolf-Hirschhorn critical regions 1 and 2 (WHSCR-1 and WHSCR-2,
      respectively), which cause cranio-facial anomalies, congenital malformations and
      developmental delay/intellectual disability. METHODS/RESULTS: We report on
      clinical findings detected in a Chinese patient with a de novo 4p16.1-p15.32
      duplication in association with a subtle 4p terminal deletion of 6 Mb in size.
      This unusual chromosome imbalance resulted in WHS classical phenotype, while
      clinical manifestations of 4p trisomy were practically absent. CONCLUSION: This
      observation suggests the hypothesis that haploinsufficiency of sensitive dosage
      genes with regulatory function placed in WHS critical region, is more pathogenic
      than concomitant 4p duplicated segment. Additionally clinical findings in our
      patient confirm a variable penetrance of major malformations and neurological
      features in Chinese children despite of WHS critical region's deletion.

PMID- 25769229
TI  - Development of next generation of therapeutic IFN-alpha2b via genetic code
      expansion.
AB  - With the aim to overcome the heterogeneity associated with marketed IFN-alpha2b
      PEGylates and optimize the size of the PEG moiety and the site of PEGylation, we
      develop a viable and facile platform through genetic code expansion for
      PEGylation of IFN-alpha2b at any chosen site(s). This approach includes site
      specific incorporation of an azide-bearing amino acid into IFN-alpha2b followed
      by orthogonal and stoichiometric conjugation of a variety of PEGs via a copper
      free click reaction. By this approach, only the chosen site(s) within IFN-alpha2b
      is consistently PEGylated under mild conditions, leading to a single and
      homogenous conjugate. Furthermore, it makes the structure-activity relationship
      study of IFN-alpha2b possible by which the opposite effects of PEGylation on the
      biological and pharmacological properties are optimized. Upon re-examination of
      the PEGylated IFN-alpha2b isomers carrying different sizes of PEG at different
      sites, we find mono-PEGylates at H34, A74 and E107 with a 20-, 10- and 10-kDa PEG
      moiety, respectively, have both higher biological activities and better PK
      profiles than others. These might represent the direction for development of the
      next generation of PEGylated IFN-alpha2b. 

PMID- 25769228
TI  - Stealth filaments: Polymer chain length and conformation affect the in vivo fate
      of PEGylated potato virus X.
AB  - Nanoparticles hold great promise for delivering medical cargos to cancerous
      tissues to enhance contrast and sensitivity of imaging agents or to increase
      specificity and efficacy of therapeutics. A growing body of data suggests that
      nanoparticle shape, in combination with surface chemistry, affects their in vivo
      fates, with elongated filaments showing enhanced tumor targeting and tissue
      penetration, while promoting immune evasion. The synthesis of high aspect ratio
      filamentous materials at the nanoscale remains challenging using synthetic
      routes; therefore we turned toward nature's materials, developing and studying
      the filamentous structures formed by the plant virus potato virus X (PVX). We
      recently demonstrated that PVX shows enhanced tumor homing in various preclinical
      models. Like other nanoparticle systems, the proteinaceous platform is cleared
      from circulation and tissues by the mononuclear phagocyte system (MPS). To
      increase bioavailability we set out to develop PEGylated stealth filaments and
      evaluate the effects of PEG chain length and conformation on pharmacokinetics,
      biodistribution, as well as potential immune and inflammatory responses. We
      demonstrate that PEGylation effectively reduces immune recognition while
      increasing pharmacokinetic profiles. Stealth filaments show reduced interaction
      with cells of the MPS; the protein:polymer hybrids are cleared from the body
      tissues within hours to days indicating biodegradability and biocompatibility.
      Tissue compatibility is indicated with no apparent inflammatory signaling in
      vivo. Tailoring PEG chain length and conformation (brush vs. mushroom) allows
      tuning of the pharmacokinetics, yielding long-circulating stealth filaments for
      applications in nanomedicine. 

PMID- 25769230
TI  - Biomimetic poly(glycerol sebacate)/poly(l-lactic acid) blend scaffolds for
      adipose tissue engineering.
AB  - Large three-dimensional poly(glycerol sebacate) (PGS)/poly(l-lactic acid) (PLLA)
      scaffolds with similar bulk mechanical properties to native low and high stress
      adapted adipose tissue were fabricated via a freeze-drying and a subsequent
      curing process. PGS/PLLA scaffolds containing 73vol.% PGS were prepared using two
      different organic solvents, resulting in highly interconnected open-pore
      structures with porosities and pore sizes in the range of 91-92% and 109-141MUm,
      respectively. Scanning electron microscopic analysis indicated that the scaffolds
      featured different microstructure characteristics, depending on the organic
      solvent in use. The PGS/PLLA scaffolds had a tensile Young's modulus of 0.030MPa,
      tensile strength of 0.007MPa, elongation at the maximum stress of 25% and full
      shape recovery capability upon release of the compressive load. In vitro
      degradation tests presented mass losses of 11-16% and 54-55% without and with the
      presence of lipase enzyme in 31days, respectively. In vitro cell tests exhibited
      clear evidence that the PGS/PLLA scaffolds prepared with 1,4-dioxane as the
      solvent are suitable for culture of adipose derived stem cells. Compared to
      pristine PLLA scaffolds prepared with the same procedure, these scaffolds
      provided favourable porous microstructures, good hydrophilic characteristics, and
      appropriate mechanical properties for soft tissue applications, as well as
      enhanced scaffold cell penetration and tissue in-growth characteristics. This
      work demonstrates that the PGS/PLLA scaffolds have potential for applications in
      adipose tissue engineering. 

PMID- 25769231
TI  - Biocompatibility of MgF2-coated MgNd2 specimens in contact with mucosa of the
      nasal sinus - a long term study.
AB  - Up to now, different surgical techniques and stent systems have already been
      developed and tested for the continuous and adequate ventilation of the frontal
      sinuses. However, the results achieved still remain poor. Magnesium-based
      implants have been successfully used in numerous clinical applications. Offering
      excellent biocompatibility and biodegradability it may be the ideal material for
      the development of novel implants of the nasal sinus. Here, we present for the
      first time results on the behaviour of magnesium alloy in a unique environment,
      i.e. in contact to the nasal mucosa, air and nasal secretion. In a prospective
      longitudinal study, magnesium fluoride-coated MgNd2 specimens were implanted in
      the frontal sinuses of 12 minipigs for the investigation of biocompatibility and
      of the interface between the implant and the mucosa. Endoscopic examinations,
      histopathological evaluation and EDX measurements were performed regularly up to
      180days. Endoscopic evaluation showed focal mucosal reaction, however, without
      affecting the patency of the sinus. In addition, no signs of bacterial infections
      were observed. The EDX analyses showed a marginal but steady increase in the Mg
      concentration in the mucosa over 180days. Histological analysis revealed a
      locally confined moderate mucosal hyperplasia and unspecific inflammatory
      reaction. Furthermore, we did not find any osteoinductive effects of the
      magnesium alloy. The results indicate the excellent biocompatibility of the MgNd2
      alloy in contact with nasal mucosa and provide a novel material compound and
      solid proof-of-principle for the development of magnesium-based nasal stents. 

PMID- 25769233
TI  - Reply: To PMID 25175496.

PMID- 25769234
TI  - Reply: To PMID 25112691.

PMID- 25769232
TI  - Novel halogenated derivates of JWH-018: Behavioral and binding studies in mice.
AB  - JWH-018 is a synthetic CB1 and CB2 agonist illegally marketed as products named
      "Spice" or "herbal blend" for its psychoactive effects which are much higher than
      those produced by cannabis. In the last year, the European Monitoring Centre for
      Drugs and Drug Addiction reported to the Italian National Early Warning System
      the seizure of plant material containing new halogenated derivatives of JWH-018
      (JWH-018 Cl and JWH-018 Br). The present study aimed to investigate the in vitro
      and in vivo activity of these two new synthetic cannabinoids in mice. In vitro
      competition binding experiments performed on mouse and human CB1 receptors
      revealed a high affinity and potency of the halogenated compounds. Synthetic
      cannabinoids (0.01-6 mg/kg i.p.) impaired motor activity and induced catalepsy in
      mice and their effects were more severe with respect to those evoked by Delta(9)
      THC. Moreover, they increased the mechanical and thermal pain threshold and
      induced a marked hypothermia. It is interesting to note that whereas high doses
      of JWH-018 cause seizures, myoclonia and hyperreflexia, the halogenated
      compounds, in particular JWH-018Br, were less effective. Behavioral and
      neurological changes were prevented by the selective CB1 receptor antagonist AM
      251. These data demonstrate for the first time that JWH-018 Cl and JWH-018 Br act
      similarly to JWH-018 while inducing less convulsive episodes and myoclonias.
      These data support the hypothesis that the halogenated compounds may have been
      introduced onto market to produce similar intoxicating effects as JWH-018 while
      causing less side effects.

PMID- 25769235
TI  - Clinical correlates of parenting stress in children with Tourette syndrome and in
      typically developing children.
AB  - OBJECTIVE: To determine the impact of tic severity in children with Tourette
      syndrome on parenting stress and the impact of comorbid attention-deficit
      hyperactivity disorder (ADHD) and obsessive-compulsive disorder (OCD)
      symptomatology on parenting stress in both children with Tourette syndrome and
      typically developing children. STUDY DESIGN: Children with diagnosed Tourette
      syndrome (n=74) and tic-free typically developing control subjects (n=48) were
      enrolled in a cross-sectional study. RESULTS: Parenting stress was greater in the
      group with Tourette syndrome than the typically developing group. Increased
      levels of parenting stress were related to increased ADHD symptomatology in both
      children with Tourette syndrome and typically developing children. Symptomatology
      of OCD was correlated with parenting stress in Tourette syndrome. Parenting
      stress was independent of tic severity in patients with Tourette syndrome.
      CONCLUSIONS: For parents of children with Tourette syndrome, parenting stress
      appears to be related to the child's ADHD and OCD comorbidity and not to the
      severity of the child's tic. Subthreshold ADHD symptomatology also appears to be
      related to parenting stress in parents of typically developing children. These
      findings demonstrate that ADHD symptomatology impacts parental stress both in
      children with and without a chronic tic disorder.

PMID- 25769237
TI  - Promises and Pitfalls: Development of the National Brachytherapy Registry.

PMID- 25769236
TI  - [The tobacco in the light of history and medicine].
AB  - Super trajectory is reported of tobacco from his first meeting with the European
      man October 15, 1492. This plant was known in Europe by the publications of the
      Sevillan physician Nicolas Monardes (1574), the relations of friar Andres Thevet
      (1575) and the famous botanical treatise of Charles de l'Ecluse (1605). The
      Swedish botanist Karl Linnaeus inclused tobacco plant in the family Solanaceae
      and deleted from this group other plants that were intermixed with it. Its
      botanical name (Nicotiana tabacum) derived from the surname of the French
      ambassador to Portugal, Jean Nicot of Villemain, who in 1560 sent it to the Queen
      Mother of France Catherine de Medicis. The use of snuff quickly spread throughout
      Europe, were it became common in the seventeenth century. By the late eighteenth
      century in New Spain, in addition to cigars, cigarettes and due in packs of
      different content the tobacco is concocted and price. The preparation of the
      different presentations of snuff, tobacco made in factories in the capital and
      several provincial cities, originated in 1796 the creation of the first
      kindergartens for the children of those working in them. This thanks to the
      successful initiative of then viceroy Marquis of Branciforte. But contrary to the
      forecasts of Father F. J. Clavijero and Mrs. F. Calderon de la Barca, wife of the
      first Spanish diplomatic representative to the government of Mexico, the use of
      tobacco, with the passage of time, far from waning has been increasing in every
      social class. And now, more than men, women are smokers. 

PMID- 25769238
TI  - The radiologist in the doctors' dining room.

PMID- 25769239
TI  - Demographics and outcomes of patients with pediatric febrile convulsive status
      epilepticus.
AB  - BACKGROUND: Convulsive status epilepticus with fever is common and may be related
      to neurological sequela in children. However, there are limited data on the
      demographics and risk factors of this phenomenon. Thus, we aimed to describe the
      demographics and risk factors of neurological sequela among children with
      convulsive status epilepticus with fever. METHODS: We reviewed convulsive status
      epilepticus with fever cases in the pediatric intensive care unit at Kobe
      Children's Hospital between 2002 and 2013. We included patients with intrinsic
      neurological disease, and excluded those with obvious central nervous system
      infection. Cases of neurological worsening were categorized as poor outcome using
      the pediatric cerebral performance category scale. Possible risk factors for poor
      outcome included age, sex, neurological medical history, seizure duration, body
      temperature, and level of consciousness. RESULTS: A total of 253 patients (128
      males), aged 1 month to 15 years (mean 45 +/- 40 months), were enrolled. Three
      patients (1.2%) died during hospitalization, and 32 (12.6%) patients had a poor
      outcome. A univariate analysis identified male sex, absence of epilepsy history,
      body temperature above 40 degrees C on admission, seizure duration longer than
      120 minutes, impaired consciousness at 12 hours after onset, and presence of
      nonconvulsive seizure as potential predictors of poor outcome. A multivariate
      analysis, revealed that an absence of epilepsy history (odds ratio = 11.18), body
      temperature above 40 degrees C on admission (odds ratio = 3.39), or impaired
      consciousness at 12 hours after onset (odds ratio = 41.85) was associated with
      poor outcome. CONCLUSIONS: Our study indicated that absence of epilepsy history,
      high temperature, and/or prolonged impaired consciousness were associated with
      brain injury.

PMID- 25769240
TI  - Anti-inflammatory effects of a novel non-antibiotic macrolide, EM900, on mucus
      secretion of airway epithelium.
AB  - OBJECTIVE: Low-dose, long-term use of 14-membered macrolides is effective for
      treatment of patients with chronic airway inflammation such as diffuse
      panbronchiolitis or chronic rhinosinusitis. However, long-term use of macrolides
      can promote the growth of drug-resistant bacteria, and the development of anti
      inflammatory macrolides that lack antibiotic effects is desirable. Previously, we
      developed EM900, a novel 12-membered erythromycin A derivative, which has potent
      anti-inflammatory and immunomodulatory activities and lacks any antibacterial
      activity. We examined the anti-inflammatory effects of EM900 on mucus secretion
      from airway epithelial cells. METHODS: To examine the in vivo effects of EM900 on
      airway inflammation, we induced hypertrophic and metaplastic changes of goblet
      cells in rat nasal epithelium via intranasal instillation of lipopolysaccharides.
      In vitro effects of EM900 on airway epithelial cells were examined using cultured
      human airway epithelial (NCI-H292) cells. Mucus secretion was evaluated via
      enzyme-linked immunosorbent assays with an anti-MUC5AC monoclonal antibody.
      RESULTS: Oral administration of EM900 or clarithromycin (CAM) significantly
      inhibited LPS-induced mucus production from rat nasal epithelium. EM900, CAM, or
      erythromycin significantly inhibited MUC5AC secretion induced by tumor necrosis
      factor-alpha from NCI-H292 cells. MUC5AC mRNA expression was also significantly
      lower in EM900-treated cells. CONCLUSION: These results indicated that a novel
      non-antibiotic macrolide, EM900 exerted direct inhibitory effects on mucus
      secretion from airway epithelial cells, and that it may have the potential to
      become a new anti-inflammatory drug for the treatment of chronic rhinosinusitis.

PMID- 25769241
TI  - Nitric oxide influences potassium currents in inner hair cells isolated from
      guinea-pig cochlea.
AB  - OBJECTIVE: Nitric oxide (NO) is a diffusible second messenger, which regulates
      neurotransmission, serving as the principal endothelium-derived relaxing factor.
      NO also acts as an ion channel modulator. Nitric oxide synthase (NOS) has been
      identified in the inner ear, although its physiological role remains unclear. In
      the present study, the effects of NO onto K currents in inner hair cells (IHCs)
      were investigated. METHODS: IHCs were acutely isolated and K currents were
      recorded by conventional whole-cell voltage-clamp recordings. NO donors sodium
      nitroprusside (SNP) were applied directly to the cells. RESULTS: In 1mM SNP
      solutions, the amplitude of outward K currents (IK,f and IK,s) reversely
      decreased; however, fast activation kinetics was preserved. In the current
      voltage relationship curves, the maximal slope conductances were 53.2nS and
      44.2nS in control solutions and 1mM SNP solutions, respectively. At the membrane
      potential of +110mV, the amplitudes of outward currents were 9.2+/-2.9nA in
      control solutions and 7.3+/-2.7nA in 1mM SNP solutions, showing a significant
      difference. CONCLUSION: NO acts as a K channel modulator in IHCs. A fast K
      current suppression may account for the high-frequency hearing impairment by the
      prevention of fast repolarization.

PMID- 25769242
TI  - Long-term results of survival analysis after a 5-year follow-up: Efficacy of
      fluoro-2-deoxy-D-glucose positron emission tomography to evaluate responses to
      concurrent chemoradiotherapy for head and neck squamous cell carcinoma.

PMID- 25769244
TI  - Transforming growth factor-beta1 regulated phosphorylated AKT and interferon
      gamma expressions are associated with epithelial cell survival in rhesus macaque
      colon explants.
AB  - Transforming growth factor-beta1 (TGF-beta1) is an important immunoregulatory
      cytokine that plays an obligate role in regulating T-cell functions. Here, we
      demonstrated the role of TGF-beta1 in regulating the survival of intestinal
      epithelial cells (ECs) in rhesus colon explant cultures using either anti-TGF
      beta1 antibody or recombinant TGF-beta1 proteins. Neutralization of endogenous
      TGF-beta1 using anti-TGF-beta1 antibodies induced apoptosis of both intestinal
      ECs and lamina propria (LP) cells. Additionally, endogenous TGF-beta1 blocking
      significantly increased expression of IFNgamma, TNFalpha, CD107a and Perforin in
      LP cells compared to media and isotype controls. A significant decrease in pAKT
      expression was detected in anti-TGF-beta1 MAbs treated explants compared to
      isotype and rTGF-beta1 protein treated explants. Our results demonstrated TGF
      beta1 regulated pAKT and IFNgamma expressions were associated with epithelial
      cell survival in rhesus macaque colon explants and suggest a potential role of
      mucosal TGF-beta1 in regulating intestinal homeostasis and EC integrity. 

PMID- 25769243
TI  - Pseudomembranous colitis.

PMID- 25769245
TI  - Progression of retinal pigment epithelial atrophy in antiangiogenic therapy of
      neovascular age-related macular degeneration.
AB  - PURPOSE: To monitor retinal pigment epithelial (RPE) atrophy progression during
      antiangiogenic therapy of neovascular age-related macular degeneration (AMD) over
      2 years using polarization-sensitive optical coherence tomography (OCT). DESIGN:
      Prospective interventional case series. METHODS: setting: Clinical practice.
      STUDY POPULATION: Thirty patients (31 eyes) with treatment-naive neovascular AMD.
      OBSERVATION PROCEDURES: Standard intravitreal therapy (0.5 mg ranibizumab) was
      administered monthly during the first year and pro re nata (PRN; as-needed)
      during the second year. Spectral-domain (SD) OCT and polarization-sensitive OCT
      (selectively imaging the RPE) examinations were performed at baseline and at 1,
      3, 6, 12, and 24 months using a standardized protocol. RPE-related changes were
      evaluated using a semi-automated polarization-sensitive OCT segmentation
      algorithm and correlated with SD OCT and fundus autofluorescence (FAF) findings.
      MAIN OUTCOME MEASURES: RPE response, geographic atrophy (GA) progression.
      RESULTS: Atrophic RPE changes included RPE thinning, RPE porosity, focal RPE
      atrophy, and development of GA. Early RPE loss (ie, RPE porosity, focal atrophy)
      increased progressively during initial monthly treatment and remained stable
      during subsequent PRN-based therapy. GA developed in 61% of eyes at month 24.
      Mean GA area increased from 0.77 mm(2) at 12 months to 1.10 mm(2) (standard
      deviation = 1.09 mm(2)) at 24 months. Reactive accumulation of RPE-related
      material at the lesion borders increased until month 3 and subsequently
      decreased. CONCLUSIONS: Progressive RPE atrophy and GA developed in the majority
      of eyes. RPE migration signifies certain RPE plasticity. Polarization-sensitive
      OCT specifically images RPE-related changes in neovascular AMD, contrary to
      conventional imaging methods. Polarization-sensitive OCT allows for precisely
      monitoring the sequence of RPE-related morphologic changes.

PMID- 25769247
TI  - New developments in Cryptosporidium research.
AB  - Cryptosporidium is an enteric parasite that is considered the second greatest
      cause of diarrhoea and death in children after rotavirus. Currently, 27 species
      are recognised as valid and of these, Cryptosporidium hominis and Cryptosporidium
      parvum are responsible for the majority of infections in humans. Molecular and
      biological studies indicate that Cryptosporidium is more closely related to
      gregarine parasites rather than to coccidians. The identification of gregarine
      like gamont stages and the ability of Cryptosporidium to complete its life cycle
      in the absence of host cells further confirm its relationship with gregarines.
      This opens new avenues into the investigation of pathogenesis, epidemiology,
      treatment and control of Cryptosporidium. Effective drug treatments and vaccines
      are not yet available due, in part, to the technical challenges of working on
      Cryptosporidium in the laboratory. Whole genome sequencing and metabolomics have
      expanded our understanding of the biochemical requirements of this organism and
      have identified new drug targets. To effectively combat this important pathogen,
      increased funding is essential.

PMID- 25769246
TI  - Prevalence of intermediate-stage age-related macular degeneration in patients
      with acquired immunodeficiency syndrome.
AB  - PURPOSE: To evaluate the prevalence of intermediate-stage age-related macular
      degeneration (AMD) in patients with acquired immunodeficiency syndrome (AIDS).
      DESIGN: Cross-sectional study of patients with AIDS enrolled in the Longitudinal
      Study of the Ocular Complications of AIDS. METHODS: Intermediate-stage AMD was
      determined from enrollment retinal photographs by graders at a centralized
      Reading Center, using the Age-Related Eye Disease Study grading system. Graders
      were masked as to clinical data. RESULTS: Of 1825 participants with AIDS and no
      ocular opportunistic infections, 9.9% had intermediate-stage AMD. Risk factors
      included age, with an odds ratio (OR) of 1.9 (95% confidence interval [CI] 1.6,
      2.3, P < .001) for every decade of age; the prevalence of AMD ranged from 4.0%
      for participants 30-39 years old to 24.3% for participants >=60 years old. Other
      risk factors included the human immunodeficiency virus (HIV) risk groups of
      injection drug use (OR = 2.4, 95% CI 1.5, 3.9, P < .001) or heterosexual contact
      (OR = 1.9, 95% CI 1.3, 2.8, P = .001). Compared with the HIV-uninfected
      population in the Beaver Dam Offspring Study, there was an approximate 4-fold
      increased age-adjusted prevalence of intermediate-stage AMD. CONCLUSIONS:
      Patients with AIDS have an increased age-adjusted prevalence of intermediate
      stage AMD compared with that found in a non-HIV-infected cohort evaluated with
      similar methods. This increased prevalence is consistent with the increased
      prevalence of other age-related diseases in antiretroviral-treated, immune
      restored, HIV-infected persons when compared to non-HIV-infected persons.

PMID- 25769248
TI  - Endoport-assisted microsurgical resection of cerebral cavernous malformations.
AB  - The aim of this case series is to describe the surgical technique and
      postoperative outcomes for endoport-assisted microsurgical resection (EAMR) of
      cerebral cavernous malformations (CCM). Significant manipulation of subcortical
      white matter tracts may be necessary for the successful resection of CCM located
      in deep brain regions. Minimally invasive neurosurgical devices such as endoport
      systems can decrease disruption of the cortex and white matter tracts overlying
      deep-seated CCM through small cranial and dural openings. The role of endoport
      technology in modern CCM surgery is incompletely understood. Three patients with
      symptomatic CCM underwent EAMR at our institution using the BrainPath endoport
      system (NICO Corporation, Indianapolis, IN, USA). Complete resection was achieved
      in two patients. One patient with a large 4.5cm callosal CCM was left with a
      small residual lesion. There were no postoperative complications and all patients
      were functionally independent (modified Rankin Scale score 2 or less) at follow
      up. Based on our initial experience with EAMR for CCM we believe the endoport can
      be an effective alternative to traditional retractor systems. Due to the nature
      of the small craniotomy and durotomy performed for endoport placement EAMR has
      the potential to improve surgical outcomes by reducing postoperative pain,
      analgesic requirements and hospital stays. Therefore, EAMR may be considered for
      appropriately selected CCM patients, although additional experience is necessary
      to improve our understanding of its role in CCM management. 

PMID- 25769249
TI  - Spinal cord compression due to brown tumor.
AB  - We report a rare case of a vertebral brown tumor causing spinal cord compression
      and resulting in progressive paraparesis in a 27-year-old female with end-stage
      renal failure, managed with hemodialysis. Urgent neurosurgical intervention and
      gross total resection resulted in complete resolution of the symptoms. 

PMID- 25769250
TI  - Influence on morbidity and mortality of neoadjuvant radiation and chemotherapy
      among cranial malignancy patients in the postoperative setting.
AB  - We sought to assess the impact of neoadjuvant therapy on 30 day mortality and
      morbidity using data from the American College of Surgeons National Surgical
      Quality Improvement Program (ACS-NSQIP). Chemotherapy and radiotherapy are both
      often indicated for treatment of cranial or systemic malignancy but can have
      significant adverse effects in the postsurgical setting. Data from 2006 to 2012
      were obtained from the national ACS-NSQIP database. A total of 1044 patients were
      identified who obtained surgery for removal of metastatic brain tumors, of whom
      127 received neoadjuvant chemotherapy and 65 neoadjuvant radiotherapy. Our
      primary outcome was 30 day mortality and secondary outcomes were 30 day surgical
      and medical morbidities. We selected previously reported preoperative variables
      to build a univariate and a multivariate model to determine preoperative
      characteristics most associated with neurosurgical mortality and morbidity. Our
      study found that neoadjuvant chemotherapy was associated with a 2.4-fold increase
      in the risk of 30 day mortality compared to the patient cohort who did not
      receive chemotherapy (p=0.023). Interestingly, there was no statistically
      significant increase in overall 30 day surgical or medical morbidity for the
      chemotherapy group. Neoadjuvant radiotherapy was not associated with an increase
      in 30 day morbidity or mortality. The significant increase in mortality
      associated with chemotherapy warrants further investigation, particularly to
      determine how to best personalize neoadjuvant chemotherapy treatment options to
      improve surgical outcomes. Neoadjuvant radiotherapy may be safer in terms of
      short-term postoperative morbidity and mortality.

PMID- 25769251
TI  - Vertebroplasty plus short segment pedicle screw fixation in a burst fracture
      model in cadaveric spines.
AB  - The current project investigates the role of vertebroplasty in supplementing
      short segment (SS) posterior instrumentation, only one level above and below a
      fracture. In the treatment of thoracolumbar burst fractures, long segment (LS)
      posterior instrumentation two levels above and below the fracture level has been
      used. In our study, burst fractures were produced at L1 in eight fresh frozen
      human cadaveric spines. The spines were then tested in three conditions: 1)
      intact, 2) after LS (T11-L3), 3) SS (T12-L2) instrumentation with pedicle screws
      and rods, and 4) short segment instrumentation plus cement augmentation of the
      fracture level (SSC). LS instrumentation was found to significantly reduce the
      motion at the instrumented level (T12-L2) as well as the levels immediately
      adjacent in flexion, extension and lateral bending. Similarly, SSC augmentation
      was found to significantly reduce the motion compared to intact at T12-L2 but
      still maintained the adjacent level motion. However, SS instrumentation alone did
      not significantly reduce the motion at T12-L2 except for left lateral bending.
      While LS instrumentation remains the most stable construct, SS instrumentation
      augmented with vertebroplasty at the fracture level increases rigidity in
      flexion, extension and right lateral bending beyond SS instrumentation alone.

PMID- 25769252
TI  - An integrative analysis of treatment, outcomes and prognostic factors for primary
      spinal anaplastic ependymomas.
AB  - The aim of this study was to elucidate the role of treatment modalities in
      primary spinal anaplastic ependymomas (PSAE) and identify promising prognostic
      factors. PSAE are rare tumors of the central nervous system with poorly
      understood clinical characteristics and treatment outcomes. We reviewed the
      literature in PubMed, Web of Science and Scopus databases to identify patients
      with PSAE. Multivariate Cox proportional hazards analysis and univariate Kaplan
      Meier analysis were performed on the PSAE patients and overall survival (OS) and
      progression-free survival (PFS) were assessed to evaluate the clinical outcomes.
      Of the 40 patients with PSAE, the tumors were mostly intramedullary (n=19; 47.5%)
      and frequently involved the thoracic cord (n=25; 62.5%). Eighteen patients
      suffered recurrence during the follow-up with a median PFS of 24 months. The 1,
      2, and 5year OS rates of the PSAE patients were 91.5%, 82.1%, and 63.1%,
      respectively. Gross total resection (GTR) was independently associated with
      prolonged PFS (hazard ratio [HR] 0.11; p=0.004) and OS (HR 0.11; p=0.003) in the
      multivariate analysis. Adjuvant radiotherapy also conferred improved PFS (HR
      0.15; p=0.008) and OS (HR 0.16; p=0.022). Age, sex, tumor location and
      chemotherapy did not influence the outcomes in this group. The results of our
      study suggest that GTR and adjuvant radiotherapy are strong prognostic indicators
      in patients with PSAE and the role of chemotherapy is yet to be defined. 

PMID- 25769253
TI  - Early clinical results with cortically based pedicle screw trajectory for fusion
      of the degenerative lumbar spine.
AB  - This study reviews the outcomes and revision rates of degenerative lumbar fusion
      surgery using cortical trajectory pedicle screws in lieu of traditional pedicle
      screw instrumentation. Pedicle screw fixation can be a challenge in patients with
      low bone mineral density. Wide posterior approaches to the lumbar spine exposing
      lateral to the facet joints and onto transverse processes causes an additional
      degree of muscular damage and blood loss not present with a simple laminectomy. A
      cortical bone trajectory pedicle screw has been proposed as an alternative to
      prevent screw pullout and decrease the morbidity associated with the wide
      posterior approach to the spine. We present a series of eight consecutive
      patients using a cortical bone trajectory instead of traditional pedicle screw
      fixation for degenerative conditions of the lumbar spine. A retrospective review
      of our institutional registry data identified eight patients who had cortical
      screws placed with the assistance of O-arm Stealth navigation (Medtronic Sofamor
      Danek, Memphis, TN, USA) from 2010-2013. We analyzed the need for revision, the
      maintenance of reduction and the incidence of screw pullout or breakage. Our
      review demonstrated that two of eight patients were revised at an average of
      12months. The reasons for these revisions were pseudarthrosis and caudal adjacent
      segment failure. All patients who were revised had frank screw loosening. We
      present early clinical results of a new technique that has been shown to have a
      better fixation profile in laboratory testing. Our less than favorable early
      clinical results should be interpreted with caution and highlight important
      technical issues which should be considered. 

PMID- 25769254
TI  - Long term efficacy and patient satisfaction of microvascular decompression and
      gamma knife radiosurgery for trigeminal neuralgia.
AB  - The aim of our study was to evaluate the long term efficacy of microvascular
      decompression (MVD) and gamma knife radiosurgery (GKRS) with respect to pain
      relief and patient satisfaction. Both these modalities are accepted modalities of
      treatment for intractable trigeminal neuralgia. We excluded deceased patients,
      those who had a prior intervention and those requiring an additional intervention
      following initial treatment. A total of 69 patients were included in the study.
      Of these, 49 patients underwent treatment by GKRS and 20 by MVD. Pain status was
      assessed using the Barrow Neurological Institute (BNI) pain scale. The median
      follow up was 5.3years. There was no significant difference between the two
      groups with respect to initial pain relief (100% MVD, 84% GKRS; p=0.055). There
      was no significant difference in pain recurrence between the two groups (39%
      GKRS, 20% MVD; p=0.133). At last follow up, 85% of patients who underwent MVD had
      total pain relief (BNI scale I) compared to only 45% of GKRS patients (p=0.002).
      There was no significant difference in the patient satisfaction with respect to
      undergoing the same procedure again (90% MVD, 69% GKRS; p=0.1) and recommending
      it to family members (95% MVD, 84% GKRS; p=0.2). MVD offered total pain relief in
      a significantly higher number of patients than GKRS. There was no significant
      difference in the patient satisfaction rate between the two groups.

PMID- 25769255
TI  - A new technique for avoiding barotrauma-induced complications in apnea testing
      for brain death.
AB  - Prompted by our experience with complications occurring with apnea testing (AT),
      we discuss complications reported in the literature. AT is an integral part of
      brain death assessment. Many complications of AT have been described, including
      hypoxemia, arterial hypotension, tension pneumothorax and cardiac arrest. We
      conclude that a commonly used technique in conducting AT can create auto-positive
      end expiratory pressure (PEEP) and contributes to many complications. The
      mechanism of occult auto-PEEP in AT is discussed. Intensive care unit patients
      may have a compensated and asymptomatic relative hypovolemia that can be
      decompensated by a small amount of auto-PEEP produced by air trapping during
      insufflating oxygen (O2) through a 7.0 endotracheal tube (ETT). It could then
      lead to decreased preload, decreased stroke volume, decreased cardiac output and
      thus, to hypotension and a compensatory tachycardia. The placement of the
      standard O2 tubing (6mm outside diameter [OD]) inside the 7.0 ETT (7mm inside
      diameter [ID]) greatly decreased the ETT lumen (73%). We changed our practice to
      instead use readily available small pressure tubing to insufflate O2 for AT to
      avoid excessive reduction in the ETT lumen. The change from standard O2 tubing
      (6mm OD) to pressure tubing (3mm OD) will greatly decrease the reduction in cross
      sectional area of 7.0 ETT lumen from 73 to 18% and avoid potential complications
      of air trapping, auto-PEEP and barotrauma. We have successfully used this new
      simple technique with readily available equipment to eliminate auto-PEEP in AT
      while preserving oxygenation. 

PMID- 25769256
TI  - Calcific emboli originating from the brachiocephalic trunk causing acute cerebral
      infarction and worm-like calcification in the right middle cerebral artery.
AB  - We report, to our knowledge, the first patient with brachiocephalic trunk
      calcified plaque causing the 'salted pretzel sign' and worm-like calcification.
      Arterial stenosis or occlusion caused by atherosclerosis and thrombosis are
      responsible for the majority of cases of cerebral infarction. However, there are
      a number of other causes. Interestingly, these findings were not observed on a CT
      scan 10 days before the stroke. Acute cerebral infarction with calcifications on
      unenhanced head CT scans should raise suspicion for disease in the carotid
      system. Identification of subtle findings of acute ischemic stroke on CT scans is
      important for early diagnosis and treatment.

PMID- 25769257
TI  - Cetuximab induced aseptic meningitis.
AB  - We report a 67-year-old man with recurrent advanced oropharyngeal squamous cell
      carcinoma who developed aseptic meningitis, with first symptoms arising
      approximately 9hours after the first administration of cetuximab, and review the
      literature to identify key signs and symptoms of this condition. Cetuximab is a
      monoclonal antibody targeting the epidermal growth factor receptor which has been
      rarely associated with aseptic meningitis. Besides the case description, a
      MEDLINE search was performed. In five patients identified in the literature and
      our patient, the leading signs and symptoms included headache, neck stiffness and
      high fever developing within a few hours of the first cetuximab administration.
      Cerebrospinal fluid (CSF) analysis revealed severe pleocytosis (range: 528
      2300/MUl) with dominance of neutrophils (?87%). Clinical recovery within 1-2weeks
      was accompanied by normalization of CSF cell count within 4-7days. Re-challenge
      with cetuximab at a reduced dose caused recurrent aseptic meningitis in one of
      three patients. In summary, aseptic meningitis is a rare complication after first
      cetuximab exposure that the clinician should be aware of. CSF analysis is the key
      to diagnosis and recovery is usually complete within days to weeks after
      withdrawal of the drug. Re-challenge may be considered but bears the risk of
      recurrence. 

PMID- 25769258
TI  - Intraoperative neurophysiologic monitoring with Hoffmann reflex during thoracic
      spine surgery.
AB  - The aim of this study was examine the role of Hoffmann reflex (H-reflex)
      monitoring in identifying intraoperative spinal cord injury and predicting
      postoperative neurological outcome in patients undergoing thoracic spine surgery.
      Despite the physiologic basis for the use of H-reflex to monitor spinal motor
      pathways, there are only a few reports highlighting its application as an
      intraoperative neuromonitoring tool. We retrospectively reviewed the electronic
      medical records of 19 consecutive patients who underwent thoracic spine surgery
      for metastatic thoracic spinal tumors between 2011 and 2013 at the MD Anderson
      Cancer Center. H-waves and somatosensory evoked potentials (SSEP) were
      simultaneously monitored in our series consisting of four female and 15 male
      patients aged 10-71 years. In 10 of 19 patients, bilateral H-waves and SSEP were
      stable throughout the monitoring. Five of 19 patients had a <50% transient
      reduction in H-wave amplitude that later returned to baseline. SSEP were absent
      from baseline throughout surgery in two of 19 patients. In our series, neither
      general anesthesia nor low dose muscle relaxants interfered with the H-waves. At
      3 and 6 month follow-ups, none of the patients exhibited new postoperative
      neurological deficits. Stable intraoperative H-waves are suggestive of preserved
      postoperative neurologic outcomes. Intraoperative H-reflex monitoring could be a
      reasonable alternative especially when motor evoked potentials are unattainable.
      Given its greater sensitivity to spinal cord ischemia, relatively low cost and
      ease of acquisition, H-reflex monitoring could be a useful adjunct in during
      thoracic spine surgeries.

PMID- 25769259
TI  - Seasonal variation in hemorrhage and focal neurologic deficit due to
      intracerebral cavernous malformations.
AB  - The objective was to determine if there was seasonal variation in the month of
      symptom onset in patients with intracerebral cavernous malformations (ICM).
      Patients seen at our institution between 1989 and 1999 with ICM identified from a
      radiologic database were included. Demographic data and symptoms at onset were
      abstracted. Symptomatic patients in this ICM database were included if the month
      of symptom onset was known. Comparison of proportions of patients presenting in
      fall and winter and during flu season were performed with the chi squared test
      and Fisher's exact test with significance at p<0.05. Of 292 patients identified,
      179 patients had symptomatic ICM. Of these, 135 patients with symptomatic ICM
      were identified for whom the exact month of symptom onset was known. Eighty-seven
      (64.4%) presented with intracerebral hemorrhage (ICH) or focal neurologic deficit
      (FND) and 48 (35.6%) due to seizures. When assessing all 135 patients, 75 (55.5%)
      presented in the fall and winter compared to the spring and summer (p=0.1962).
      Eighty-three (61.4%) patients presented during flu season (p=0.0074). When
      assessing only those initially presenting with ICH or FND, 53 (60.9%) patients
      presented in the fall and winter compared to spring and summer (p=0.041) and 54
      (62.8%) presented during flu season (p=0.017). Patients with recurrent ICH more
      commonly presented in the fall and winter compared to summer and spring and
      during flu season. Patients with ICM who presented with FND or ICH or had
      recurrent ICH tended to present in the fall and winter or during flu season. 

PMID- 25769261
TI  - Erratum.

PMID- 25769260
TI  - Progressive post traumatic tearing of an arachnoid cyst membrane resulting in
      intracystic and subdural haemorrhage.
AB  - We report the case of a 43-year-old man with a middle cranial fossa arachnoid
      cyst who presented post trauma with neurological symptoms. The initial CT scan of
      the brain did not detect acute changes in the arachnoid cyst but subsequent
      imaging revealed abnormalities which progressed over time. Arachnoid cysts are
      usually a benign and incidental finding. Rare complications such as intracystic
      haemorrhage and subdural haemorrhage can occur. It is important to be aware of
      these complications so that patients with arachnoid cysts are appropriately
      investigated when presenting with neurological symptoms.

PMID- 25769262
TI  - The Unique and Combined Effects of Apathy and Depression on Cognition in
      Parkinson's Disease.
AB  - BACKGROUND: Apathy and depression are associated with poor cognition in patients
      with Parkinson's disease (PD). However, the cognitive signature of each syndrome
      is not well understood. The cognitive consequences of having apathy or
      depression, versus apathy and depression, are also unclear. OBJECTIVE: This study
      investigated the unique and combined effects of apathy and depression on
      cognition in PD patients. METHODS: PD patients were identified from a clinical
      research database as having self-reported apathy (n = 21), depression (n = 11),
      or both (n = 43). PD patients without apathy or depression served as the Control
      group (n = 49). The groups were of similar age, education, disease severity, age
      of symptom onset, and medication status. A multivariate analysis of variance
      (MANOVA) compared the groups on 17 neuropsychological test scores in the domains
      of attention, motor and psychomotor speed, construction, language, episodic
      memory, and executive functioning. RESULTS: There was a significant overall
      effect of group: F(18,276) = 2.12, p = 0.006, etap2=0.12. Univariate analyses and
      planned contrasts revealed medium-sized effects distinguishing only the control
      group and the group with both apathy and depression (etap2=0.06-0.12) on measures
      of verbal fluency and manual, processing, and psychomotor speed. CONCLUSIONS: PD
      patients with apathy alone or depression alone did not perform worse than PD
      controls on neuropsychological tests. Patients with apathy and depression
      performed worse than controls, but only on speed-based measures. This suggests
      that apathy and depression are associated with the same or similar circuits as
      those of cognitive and motor speed.

PMID- 25769263
TI  - Periodontal progression based on radiographic records: An observational study in
      chronic and aggressive periodontitis.
AB  - OBJECTIVES: The current classification assumes that aggressive periodontitis
      (AgP) has a faster rate of progression than chronic periodontitis (CP). However,
      this has not been clearly proven and difficulties exist in establishing
      progression. This study aimed to assess the feasibility of retrospectively
      utilising previous records for clinical diagnosis of periodontal diseases and to
      assess if two different patterns of disease progression exist between AgP and CP.
      MATERIALS AND METHODS: Previous radiographic records of a cohort of 235 patients
      clinically diagnosed with AgP or CP were requested from the referring general
      dental practitioners (GDPs). Comparable radiographic records were analysed in
      order to assess progression patterns and associate these with clinical diagnosis,
      by multilevel analysis. RESULTS: 43 patients out of the initial 235 had
      comparable radiographs retrieved from the GDPs. 858 sites were followed for an
      average 6.6 years. Radiographically, AgP showed a faster linear pattern of
      progression than CP (0.31mm/year vs. 0.20mm/year, p<0.001). CONCLUSION: This
      study provides evidence for a faster disease progression in untreated AgP
      compared to CP as assessed by radiographic bone levels. Furthermore, it shows
      that retrievability of previous radiographs from GDPs is unpredictable and GDPs
      should be encouraged to send them along with their referral. CLINICAL
      SIGNIFICANCE: The importance of differentially diagnosing AgP and CP might be
      useful in establishing a clinically relevant definition for periodontal disease
      progression and may have an impact on the clinical management of aggressive
      periodontitis, since our findings show that there is continuous destruction in
      patients with aggressive periodontitis if left untreated.

PMID- 25769264
TI  - Impact of periodontal status on oral health-related quality of life in patients
      with and without type 2 diabetes.
AB  - OBJECTIVES: To investigate the impact of periodontal status on oral health
      related quality of life (OHRQoL) in patients with and without type 2 diabetes
      mellitus (T2DM). METHODS: 61 patients with T2DM and 74 non-diabetic patients
      matched for age, gender and periodontal status (health, gingivitis, chronic
      periodontitis) were recruited. The oral health impact profile (OHIP)-49 was self
      completed by all participants at baseline and by the patients with periodontitis
      at 3 months and 6 months after non-surgical periodontal therapy. RESULTS: There
      were no significant differences in the overall OHIP-49 summary scores between
      patients with T2DM (median; interquartile range; 37.0; 19.5-61.0) and without
      T2DM (30.4; 16.8-51.0) (p>0.05). Among non-diabetic patients, there were
      significantly higher OHIP-49 scores (indicating poorer OHRQoL) in patients with
      gingivitis (41.0; 19.7-75.7) and periodontitis (33.0; 19.9-52.5) compared to
      patients who were periodontally healthy (11.1; 7.1-34.5) (p<0.05), though such an
      effect was not observed in the patients with diabetes. In the non-diabetic
      patients with periodontitis, statistically significant reductions in OHIP-49
      scores were noted in the psychological discomfort and psychological disability
      domains following periodontal treatment, indicating an improvement in OHRQoL. In
      contrast, there were no statistically significant changes in OHIP-49 scores
      following periodontal treatment in the patients with diabetes. CONCLUSION: T2DM
      does not impact on overall OHRQoL as measured by OHIP-49. Chronic periodontitis
      and gingivitis were associated with poorer OHRQoL in non-diabetic patients, with
      evidence of improvements following periodontal treatment, but no such effects
      were observed in patients with diabetes. CLINICAL SIGNIFICANCE: Gingivitis and
      periodontitis are associated with reduced OHRQoL compared to periodontal health
      in non-diabetic patients, with improvements following treatment of periodontitis.
      No impact of type 2 diabetes on OHRQoL was noted; this may be related to the
      burden of chronic disease (diabetes) minimising the impact of oral health issues
      on OHRQoL.

PMID- 25769265
TI  - Penetration of micro-filled infiltrant resins into artificial caries lesions.
AB  - OBJECTIVES: Infiltrants are non-filled low-viscosity resins that have been
      developed to arrest lesion progression by penetrating into the porosities of non
      cavitated lesions where they are hardened and arrest lesion progression. The
      addition of fillers to infiltrant resin might combine the high penetrativity of
      the former with the better applicability of composite resins. The aim of the
      present study was to evaluate the penetration of different experimental micro
      filled infiltrant resins (MFIRs) into artificial enamel lesions. METHODS: An
      infiltrant (Icon; DMG) was mixed with either one of three fillers [OF83: organic
      filler (83MUm), OF42: organic filler (42MUm) or GF0.7: glass filler (0.7MUm)]
      reaching 35, 45 and 55% filler content, respectively. In each of 180 bovine
      enamel specimens three artificial lesions were created; two lesions were etched
      for 5s (37% H3PO4), leaving one lesion as control. Specimens were randomly
      allocated to 10 groups, in which either one of the MFIRs or the infiltrant was
      applied onto the two etched lesions for either 5s or 10s (n=18/group). Percentage
      of penetration (PP) was calculated and analysed. RESULTS: For both application
      times a significant influence of filler size but not of filler concentration on
      PP could be revealed (p<0.05; two-way ANOVA). PP of MFIRs-OF42 was not
      significantly different from unfilled infiltrant but significantly higher than
      those of OF83 and GF0.7 (p<0.05; two-way ANOVA). CONCLUSIONS: MFIRs-OF42 showed
      the ability to penetrate into artificial enamel caries lesions similar to the
      unfilled infiltrant resin. CLINICAL SIGNIFICANCE: MFIRs could provide a new micro
      invasive treatment for small-cavitated lesions.

PMID- 25769267
TI  - Improving diagnosis of childhood pneumonia.

PMID- 25769266
TI  - Gut bacteria in children with autism spectrum disorders: challenges and promise
      of studying how a complex community influences a complex disease.
AB  - Recent studies suggest a role for the microbiota in autism spectrum disorders
      (ASD), potentially arising from their role in modulating the immune system and
      gastrointestinal (GI) function or from gut-brain interactions dependent or
      independent from the immune system. GI problems such as chronic constipation
      and/or diarrhea are common in children with ASD, and significantly worsen their
      behavior and their quality of life. Here we first summarize previously published
      data supporting that GI dysfunction is common in individuals with ASD and the
      role of the microbiota in ASD. Second, by comparing with other publically
      available microbiome datasets, we provide some evidence that the shifted
      microbiota can be a result of westernization and that this shift could also be
      framing an altered immune system. Third, we explore the possibility that gut
      brain interactions could also be a direct result of microbially produced
      metabolites. 

PMID- 25769268
TI  - Severe liver fibrosis caused by Schistosoma mansoni: management and treatment
      with a transjugular intrahepatic portosystemic shunt.
AB  - Liver diseases are common in inhabitants and migrants of tropical countries,
      where the liver can be exposed not only to toxins but also to many viral,
      bacterial, fungal, and parasitic infections. Schistosomiasis--a common parasitic
      infection that affects at least 240 million people worldwide, mostly in Africa-
      is regarded as the most frequent cause of liver fibrosis worldwide. We present a
      case of a 19-year-old male refugee from Guinea with recurrent oesophageal
      variceal bleeding due to schistosomal liver fibrosis refractory to endoscopic
      therapy. This case was an indication for portosystemic surgery, which is a highly
      invasive non-reversible intervention. An alternative, less invasive, reversible
      radiological procedure, used in liver cirrhosis, is the placement of a
      transjugular intrahepatic portosystemic shunt (TIPS). After thorough
      considerations of all therapeutic options we placed a TIPS in our patient. In
      more than 3 years of observation, he is clinically well apart from one episode of
      hepatic encephalopathy related to an acute episode of viral gastroenteritis.
      Bleeding from oesophageal varices has not recurred. In this Grand Round, we
      review the diagnostic approaches and treatment options for portal hypertension
      due to schistosomal liver fibrosis.

PMID- 25769269
TI  - Clinical features for diagnosis of pneumonia in children younger than 5 years: a
      systematic review and meta-analysis.
AB  - BACKGROUND: Pneumonia is the biggest cause of deaths in young children in
      developing countries, but early diagnosis and intervention can effectively reduce
      mortality. We aimed to assess the diagnostic value of clinical signs and symptoms
      to identify radiological pneumonia in children younger than 5 years and to review
      the accuracy of WHO criteria for diagnosis of clinical pneumonia. METHODS: We
      searched Medline (PubMed), Embase (Ovid), the Cochrane Database of Systematic
      Reviews, and reference lists of relevant studies, without date restrictions, to
      identify articles assessing clinical predictors of radiological pneumonia in
      children. Selection was based on: design (diagnostic accuracy studies), target
      disease (pneumonia), participants (children aged <5 years), setting (ambulatory
      or hospital care), index test (clinical features), and reference standard (chest
      radiography). Quality assessment was based on the 2011 Quality Assessment of
      Diagnostic Accuracy Studies (QUADAS-2) criteria. For each index test, we
      calculated sensitivity and specificity and, when the tests were assessed in four
      or more studies, calculated pooled estimates with use of bivariate model and
      hierarchical summary receiver operation characteristics plots for meta-analysis.
      FINDINGS: We included 18 articles in our analysis. WHO-approved signs age-related
      fast breathing (six studies; pooled sensitivity 0.62, 95% CI 0.26-0.89;
      specificity 0.59, 0.29-0.84) and lower chest wall indrawing (four studies; 0.48,
      0.16-0.82; 0.72, 0.47-0.89) showed poor diagnostic performance in the meta
      analysis. Features with the highest pooled positive likelihood ratios were
      respiratory rate higher than 50 breaths per min (1.90, 1.45-2.48), grunting
      (1.78, 1.10-2.88), chest indrawing (1.76, 0.86-3.58), and nasal flaring (1.75,
      1.20-2.56). Features with the lowest pooled negative likelihood ratio were cough
      (0.30, 0.09-0.96), history of fever (0.53, 0.41-0.69), and respiratory rate
      higher than 40 breaths per min (0.43, 0.23-0.83). INTERPRETATION: Not one
      clinical feature was sufficient to diagnose pneumonia definitively. Combination
      of clinical features in a decision tree might improve diagnostic performance, but
      the addition of new point-of-care tests for diagnosis of bacterial pneumonia
      would help to attain an acceptable level of accuracy. FUNDING: Swiss National
      Science Foundation.

PMID- 25769271
TI  - A dual-task paradigm for behavioral and neurobiological studies in nonhuman
      primates.
AB  - BACKGROUND: The dual-task paradigm is a procedure in which subjects are asked to
      perform two behavioral tasks concurrently, each of which involves a distinct goal
      with a unique stimulus-response association. Due to the heavy demand on subject's
      cognitive abilities, human studies using this paradigm have provided detailed
      insights regarding how the components of cognitive systems are functionally
      organized and implemented. Although dual-task paradigms are widely used in human
      studies, they are seldom used in nonhuman animal studies. NEW METHOD: We propose
      a novel dual-task paradigm for monkeys that requires the simultaneous performance
      of two cognitively demanding component tasks, each of which uses an independent
      effector for behavioral responses (hand and eyes). We provide a detailed
      description of an optimal training protocol for this paradigm, which has been
      lacking in the existing literature. RESULTS: An analysis of behavioral
      performance showed that the proposed dual-task paradigm (1) was quickly learned
      by monkeys (less than 40 sessions) with step-by-step training protocols, (2)
      produced specific behavioral effects, known as dual-task interference in human
      studies, and (3) achieved rigid and independent control of the effectors for
      behavioral responses throughout the trial. COMPARISON WITH EXISTING METHODS: The
      proposed dual-task paradigm has a scalable task structure, in that each of the
      two component tasks can be easily replaced by other tasks, while preserving the
      overall structure of the paradigm. CONCLUSIONS: This paradigm should be useful
      for investigating executive control that underlies dual-task performance at both
      the behavioral and neuronal levels.

PMID- 25769272
TI  - Cross-correlation of bio-signals using continuous wavelet transform and genetic
      algorithm.
AB  - BACKGROUND: Continuous wavelet transform allows to obtain time-frequency
      representation of a signal and analyze short-lived temporal interaction of
      concurrent processes. That offers good localization in both time and frequency
      domain. Scalogram and coscalogram analysis of two signal interaction dynamics
      gives an indication of the cross-correlation of analyzed signals in both domains.
      NEW METHODS: We have used genetic algorithm with a fitness function based on
      signals convolution to find time delay between investigated signals. Two methods
      of cross-correlation are proposed: one that finds single delay for analyzed
      signals, and one returns a vector of delay values for each of wavelet transform
      sub-band center frequencies. Algorithms were implemented using MATLAB. RESULTS:
      We have extracted the data of simultaneously recorded encephalogram and arterial
      blood pressure and have investigated their interaction dynamics. We found time
      delay whose value cannot be precisely determined by scalograms and coscalogram
      inspection. The biomedical signals used come from MIMIC database. COMPARISON WITH
      EXISTING METHOD(S): Cross-correlation of two complex signals is commonly
      performed using fast Fourier transform. It works well for signals with invariant
      frequency content. We have determined the time delay between analyzed signals
      using wavelet scalograms and we have accordingly shifted one of them, aligning
      associated events. Their coscalogram indicates the cross-correlation of the
      associated events. CONCLUSION: Introducing new methods of wavelet transform in
      cross-correlation analysis has proven to be beneficial to the gain of the
      information about process interaction. Introduced solutions could be used to
      reason about causality between processes and gain bigger insight regarding
      analyzed systems.

PMID- 25769270
TI  - Animal models of temporal lobe epilepsy following systemic chemoconvulsant
      administration.
AB  - In order to understand the pathophysiology of temporal lobe epilepsy (TLE), and
      thus to develop new pharmacological treatments, in vivo animal models that
      present features similar to those seen in TLE patients have been developed during
      the last four decades. Some of these models are based on the systemic
      administration of chemoconvulsants to induce an initial precipitating injury
      (status epilepticus) that is followed by the appearance of recurrent seizures
      originating from limbic structures. In this paper we will review two chemically
      induced TLE models, namely the kainic acid and pilocarpine models, which have
      been widely employed in basic epilepsy research. Specifically, we will take into
      consideration their behavioral, electroencephalographic and neuropathologic
      features. We will also evaluate the response of these models to anti-epileptic
      drugs and the impact they might have in developing new treatments for TLE. 

PMID- 25769273
TI  - Efficient semi-automatic 3D segmentation for neuron tracing in electron
      microscopy images.
AB  - BACKGROUND: In the area of connectomics, there is a significant gap between the
      time required for data acquisition and dense reconstruction of the neural
      processes contained in the same dataset. Automatic methods are able to eliminate
      this timing gap, but the state-of-the-art accuracy so far is insufficient for use
      without user corrections. If completed naively, this process of correction can be
      tedious and time consuming. NEW METHOD: We present a new semi-automatic method
      that can be used to perform 3D segmentation of neurites in EM image stacks. It
      utilizes an automatic method that creates a hierarchical structure for
      recommended merges of superpixels. The user is then guided through each predicted
      region to quickly identify errors and establish correct links. RESULTS: We tested
      our method on three datasets with both novice and expert users. Accuracy and
      timing were compared with published automatic, semi-automatic, and manual
      results. COMPARISON WITH EXISTING METHODS: Post-automatic correction methods have
      also been used in Mishchenko et al. (2010) and Haehn et al. (2014). These methods
      do not provide navigation or suggestions in the manner we present. Other semi
      automatic methods require user input prior to the automatic segmentation such as
      Jeong et al. (2009) and Cardona et al. (2010) and are inherently different than
      our method. CONCLUSION: Using this method on the three datasets, novice users
      achieved accuracy exceeding state-of-the-art automatic results, and expert users
      achieved accuracy on par with full manual labeling but with a 70% time
      improvement when compared with other examples in publication.

PMID- 25769274
TI  - On the identification of sleep stages in mouse electroencephalography time
      series.
AB  - The automatic identification of sleep stages in electroencephalography (EEG) time
      series is a long desired goal for researchers concerned with the study of sleep
      disorders. This paper presents advances towards achieving this goal, with
      particular application to EEG time-series recorded from mice. Approaches in the
      literature apply supervised learning classifiers, however, these do not reach the
      performance levels required for use within a laboratory. In this paper, detection
      reliability is increased, most notably in the case of REM stage identification,
      by naturally decomposing the problem and applying a support vector machine (SVM)
      based classifier to each of the EEG channels. Their outputs are integrated within
      a multiple classifier system. Furthermore, there exists no general consensus on
      the ideal choice of parameter values in such systems. Therefore, an investigation
      into the effects upon the classification performance is presented by varying
      parameters such as the epoch length; features size; number of training samples;
      and the method for calculating the power spectral density estimate. Finally, the
      results of these investigations are brought together to demonstrate the
      performance of the proposed classification algorithm in two cases: intra-animal
      classification and inter-animal classification. It is shown that, within a
      dataset of 10 EEG recordings, and using less than 1% of an EEG as training data,
      a mean classification errors of Awake 6.45%, NREM 5.82%, and REM 6.65% (with
      standard deviations less than 0.6%) are achieved in intra-animal analysis and,
      when using the equivalent of 7% of one EEG as training data, Awake 10.19%, NREM
      7.75%, and REM 17.43% are achieved in inter-animal analysis (with mean standard
      deviations of 6.42%, 2.89%, and 9.69% respectively). A software package
      implementing the proposed approach will be made available through Cybula Ltd. 

PMID- 25769275
TI  - The Neuro-spheroid--A novel 3D in vitro model for peripheral nerve regeneration.
AB  - BACKGROUND: In order to reduce in vivo animal experiments in peripheral nerve
      regeneration research, in vitro models are desirable. Common two dimensional (2D)
      co-culture models lack the complex interactions of three dimensional (3D)
      physiological structures. The aim of the study was to establish a neuronal 3D
      spheroidal sprouting assay for peripheral nerve regeneration. NEW METHOD:
      Spheroids consisting of Schwann cells (SC, 500 cells/spheroid) and NG108-15 cells
      (NG, 50 cells/spheroid), a hybrid cell line, were formed in hanging drops and
      were embedded in a 3D collagen matrix. Spheroid sprout lengths were compared to
      those of the neurites of NG in a 2D co-culture with SC. Lengths were measured
      using phase contrast images taken every day over 10 days. Additionally we took
      fluorescence images to visualize the PKH26-labeled NG in both culture systems.
      RESULTS: Initially thin neurites grew out in both co-cultures, over time the
      sprouts' diameter in the 3D culture increased. The direct comparison of the
      sprout length revealed significantly longer neurites in the 3D co-culture from
      day 7 until day 10 (p<0.001). COMPARISON WITH EXISTING METHODS: Other co-culture
      models either display processes in 2D or need complex matrices to create 3D
      structures. Our spheroidal model is easy to establish, highly flexible and
      nevertheless 3D. CONCLUSIONS: The 3D-Schwann cell-neuron spheroid model shows
      that by simply transferring a 2D into a 3D co-culture with multiplication of cell
      cell contacts, a significant increase of neurite length can be achieved. The
      model is a relatively simple method for the investigation of neurite development
      in vitro.

PMID- 25769276
TI  - Hand-in-hand advances in biomedical engineering and sensorimotor restoration.
AB  - BACKGROUND: Living in a multisensory world entails the continuous sensory
      processing of environmental information in order to enact appropriate motor
      routines. The interaction between our body and our brain is the crucial factor
      for achieving such sensorimotor integration ability. Several clinical conditions
      dramatically affect the constant body-brain exchange, but the latest developments
      in biomedical engineering provide promising solutions for overcoming this
      communication breakdown. NEW METHOD: The ultimate technological developments
      succeeded in transforming neuronal electrical activity into computational input
      for robotic devices, giving birth to the era of the so-called brain-machine
      interfaces. Combining rehabilitation robotics and experimental neuroscience the
      rise of brain-machine interfaces into clinical protocols provided the
      technological solution for bypassing the neural disconnection and restore
      sensorimotor function. RESULTS: Based on these advances, the recovery of
      sensorimotor functionality is progressively becoming a concrete reality. However,
      despite the success of several recent techniques, some open issues still need to
      be addressed. COMPARISON WITH EXISTING METHOD(S): Typical interventions for
      sensorimotor deficits include pharmaceutical treatments and manual/robotic
      assistance in passive movements. These procedures achieve symptoms relief but
      their applicability to more severe disconnection pathologies is limited (e.g.
      spinal cord injury or amputation). CONCLUSIONS: Here we review how state-of-the
      art solutions in biomedical engineering are continuously increasing expectances
      in sensorimotor rehabilitation, as well as the current challenges especially with
      regards to the translation of the signals from brain-machine interfaces into
      sensory feedback and the incorporation of brain-machine interfaces into daily
      activities.

PMID- 25769277
TI  - An automated behavioral box to assess forelimb function in rats.
AB  - BACKGROUND: Rodent forelimb reaching behaviors are commonly assessed using a
      single-pellet reach-to-grasp task. While the task is widely recognized as a very
      sensitive measure of distal limb function, it is also known to be very labor
      intensive, both for initial training and the daily assessment of function. NEW
      METHOD: Using components developed by open-source electronics platforms, we have
      designed and tested a low-cost automated behavioral box to measure forelimb
      function in rats. Our apparatus, made primarily of acrylic, was equipped with
      multiple sensors to control the duration and difficulty of the task, detect reach
      outcomes, and dispense pellets. Our control software, developed in MATLAB, was
      also used to control a camera in order to capture and process video during
      reaches. Importantly, such processing could monitor task performance in near real
      time. RESULTS: We further demonstrate that the automated apparatus can be used to
      expedite skill acquisition, thereby increasing throughput as well as facilitating
      studies of early versus late motor learning. The setup is also readily compatible
      with chronic electrophysiological monitoring. COMPARISON WITH EXISTING METHODS:
      Compared to a previous version of this task, our setup provides a more efficient
      method to train and test rodents for studies of motor learning and recovery of
      function after stroke. The unbiased delivery of behavioral cues and outcomes also
      facilitates electrophysiological studies. CONCLUSIONS: In summary, our automated
      behavioral box will allow high-throughput and efficient monitoring of rat
      forelimb function in both healthy and injured animals.

PMID- 25769278
TI  - Fluorescence lifetime imaging ophthalmoscopy in type 2 diabetic patients who have
      no signs of diabetic retinopathy.
AB  - The time-resolved autofluorescence of the eye is used for the detection of
      metabolic alteration in diabetic patients who have no signs of diabetic
      retinopathy. One eye from 37 phakic and 11 pseudophakic patients with type 2
      diabetes, and one eye from 25 phakic and 23 pseudophakic healthy subjects were
      included n the study. After a three-exponential fit of the decay of
      autofluorescence, histograms of lifetimes tau(i), amplitudes alpha(i), and
      relative contributions Q(i) were statistically compared between corresponding
      groups in two spectral channels (490 < ch1 < 560 nm, 560 < ch2 < 700 nm). The
      change in single fluorophores was estimated by applying the Holm-Bonferroni
      method and by calculating differences in the sum histograms of lifetimes. Median
      and mean of the histograms of tau(2), tau(3), and alpha(3) in ch1 show the
      greatest differences between phakic diabetic patients and age-matched controls (p
      < 0.000004). The lack of pixels with a tau(2) of ~360 ps, the increased number of
      pixels with tau(2) > 450 ps, and the shift of tau(3) from ~3000 to 3700 ps in ch1
      of diabetic patients when compared with healthy subjects indicate an increased
      production of free flavin adenine dinucleotide, accumulation of advanced
      glycation end products (AGE), and, probably, a change from free to protein-bound
      reduced nicotinamide adenine inucleotide at the fundus. AGE also accumulated in
      the crystalline lens.

PMID- 25769279
TI  - Distinguishing rhythmic from non-rhythmic brain activity during rest in healthy
      neurocognitive aging.
AB  - Rhythmic brain activity at low frequencies (<12Hz) during rest are thought to
      increase in neurodegenerative disease, but findings in healthy neurocognitive
      aging are mixed. Here we address two reasons conventional spectral analyses may
      have led to inconsistent results. First, spectral-power measures are compared to
      a baseline condition; when resting activity is the signal of interest, it is
      unclear what the baseline should be. Second, conventional methods do not clearly
      differentiate power due to rhythmic versus non-rhythmic activity. The Better
      OSCillation detection method (BOSC; Caplan et al., 2001; Whitten et al., 2011)
      avoids these problems by using the signal's own spectral characteristics as a
      reference to detect elevations in power lasting a few cycles. We recorded
      electroencephalographic (EEG) signal during rest, alternating eyes open and
      closed, in healthy younger (18-25 years) and older (60-74 years) participants.
      Topographic plots suggested the conventional and BOSC analyses measured different
      sources of activity, particularly at frequencies, like delta (1-4Hz), at which
      rhythms are sporadic; topographies were more similar in the 8-12Hz alpha band.
      There was little theta-band activity meeting the BOSC method's criteria,
      suggesting prior findings of theta power in healthy aging may reflect non
      rhythmic signal. In contrast, delta oscillations were present at higher levels
      than theta in both age groups. In summary, applying strict and standardized
      criteria for rhythmicity, slow rhythms appear present in the resting brain at
      delta and alpha, but not theta frequencies, and appear unchanged in healthy
      aging. 

PMID- 25769280
TI  - Parametric variation of gamma frequency and power with luminance contrast: A
      comparative study of human MEG and monkey LFP and spike responses.
AB  - Gamma oscillations contribute significantly to the manner in which neural
      activity is bound into functional assemblies. The mechanisms that underlie the
      human gamma response, however, are poorly understood. Previous computational
      models of gamma rely heavily on the results of invasive recordings in animals,
      and it is difficult to assess whether these models hold in humans. Computational
      models of gamma predict specific changes in gamma spectral response with
      increased excitatory drive. Hence, differences and commonalities between spikes,
      LFPs and MEG in the spectral responses to changes in excitatory drive can lead to
      a refinement of existing gamma models. We compared gamma spectral responses to
      varying contrasts in a monkey dataset acquired previously (Roberts et al., 2013)
      with spectral responses to similar contrast variations in a new human MEG
      dataset. We found parametric frequency shifts with increasing contrast in human
      MEG at the single-subject and the single-trial level, analogous to those observed
      in the monkey. Additionally, we observed parametric modulations of spectral
      asymmetry, consistent across spikes, LFP and MEG. However, while gamma power
      scaled linearly with contrast in MEG, it saturated at high contrasts in both the
      LFP and spiking data. Thus, while gamma frequency changes to varying contrasts
      were comparable across spikes, LFP and MEG, gamma power changes were not. This
      indicates that gamma frequency may be a more stable parameter across scales of
      measurements and species than gamma power. The comparative approach undertaken
      here represents a fruitful path towards a better understanding of gamma
      oscillations in the human brain. 

PMID- 25769281
TI  - Biodegradable polymeric nanoparticles for oral delivery of epirubicin: In vitro,
      ex vivo, and in vivo investigations.
AB  - Epirubicin (EPI) is an anthracycline antineoplastic agent, commercially available
      for intravenous administration only and its oral ingestion continues to remain a
      challenge. Present investigation is aimed at the development of poly-lactic-co
      glycolic acid (PLGA) nanoparticles (NPs) for oral bioavailability enhancement of
      epirubicin. Developed formulation revealed particle size, 235.3+/-15.12 nm, zeta
      potential, -27.5+/-0.7 mV and drug content (39.12+/-2.13 MUg/mg), with spherical
      shape and smooth surface. Cytotoxicity studies conducted on human breast
      adenocarcinoma cell lines (MCF-7) confirmed the superiority of epirubicin loaded
      poly-lactic-co-glycolic acid nanoparticles (EPI-NPs) over free epirubicin
      solution (EPI-S). Further, flow cytometric analysis demonstrated improved drug
      uptake through EPI-NPs and elucidated the dominance of caveolae mediated
      endocytosis for nanoparticles uptake. Transport study accomplished on human colon
      adenocarcinoma cell line (Caco-2) showed 2.76 fold improvement in permeability
      for EPI-NPs as compared to EPI-S (p<0.001) whereas a 4.49 fold higher transport
      was observed on rat ileum; a 1.8 fold higher (p<0.01) in comparison to Caco-2
      cell lines which confirms the significant role of Peyer's patches in absorption
      enhancement. Furthermore, in vivo pharmacokinetic studies also revealed 3.9 fold
      improvement in oral bioavailability of EPI through EPI-NPs. Henceforth, EPI-NPs
      is a promising approach to replace pre-existing intravenous therapy thus
      providing "patient care at home".

PMID- 25769282
TI  - Sulfisoxazole/cyclodextrin inclusion complex incorporated in electrospun
      hydroxypropyl cellulose nanofibers as drug delivery system.
AB  - Herein, hydroxypropyl-beta-cyclodextrin (HPbetaCD) inclusion complex (IC) of a
      hydrophobic drug, sulfisoxazole (SFS) was incorporated in hydroxypropyl cellulose
      (HPC) nanofibers (HPC/SFS/HPbetaCD-IC-NF) via electrospinning. SFS/HPbetaCD-IC
      was characterized by DSC to investigate the formation of inclusion complex and
      the stoichiometry of the complex was determined by Job's plot. Modeling studies
      were also performed on SFS/HPbetaCD-IC using ab initio technique. SEM images
      depicted the defect free uniform fibers and confirmed the incorporation of
      SFS/HPbetaCD-IC in nanofibers did not alter the fiber morphology. XRD analyses
      showed amorphous distribution of SFS/HPbetaCD-IC in the fiber mat. Release
      studies were performed in phosphate buffered saline (PBS). The results suggest
      higher amount of SFS released from HPC/SFS/HPbetaCD-IC-NF when compared to free
      SFS containing HPC nanofibers (HPC/SFS-NF). This was attributed to the increased
      solubility of SFS by inclusion complexation. Sandwich configurations were
      prepared by placing HPC/SFS/HPbetaCD-IC-NF between electrospun PCL nanofibrous
      mat (PCL-HPC/SFS/HPbetaCD-IC-NF). Consequently, PCL-HPC/SFS/HPbetaCD-IC-NF
      exhibited slower release of SFS as compared with HPC/SFS/HPbetaCD-IC-NF. This
      study may provide more efficient future strategies for developing delivery
      systems of hydrophobic drugs. 

PMID- 25769283
TI  - Surface charge effect on mucoadhesion of chitosan based nanogels for local anti
      colorectal cancer drug delivery.
AB  - To develop more effective anticancer mucoadhesive drug delivery system for the
      treatment of colorectal cancer, chitosan based nanogels (NGs) were prepared by
      electrostatic interaction between chitosan (CS) and carboxymethyl-chitosan
      (CMCS). By respectively using tripolyphosphate (TPP) and CaCl2 as ionic
      crosslinker, two well-characterized doxorubicin hydrochloride (DOX) loaded NGs
      with opposite zeta potential (DOX:CS/CMCS/TPP NGs, -32.6+/-1.1 mV and
      DOX:CS/CMCS/Ca2+ NGs, +31.8+/-0.9 mV) were obtained. Compared with
      DOX:CS/CMCS/TPP NGs, DOX:CS/CMCS/Ca2+ NGs were taken up to a greater extent by
      colorectal cancer cells, resulting in greater reduction in percentage of cell
      viability. Owing to high binding capability to mucin and inhibited paracellular
      transport by colon, DOX:CS/CMCS/Ca2+ NGs exhibited improved mucoadhesion and
      limited permeability. This is beneficial to prolong the contact time of
      formulation onto intestinal mucosa and improved local drug concentration. The
      results provided evidence DOX:CS/CMCS/Ca2+ NGs to be exciting and promising for
      the treatment of colorectal cancer.

PMID- 25769284
TI  - Obstructive jaundice caused by pancreaticoduodenal artery aneurysms associated
      with celiac axis stenosis: case report and review of the literature.
AB  - Pancreaticoduodenal artery aneurysm (PDA) is quite rare, which accounts for only
      approximate 2% of all visceral aneurysms. Besides, PDA is usually related to
      celiac axis stenosis (CAS) and prone to rupture. Advanced imaging examination can
      facilitate the disclosure of such peripancreatic masses, but most of them were
      seldom diagnosed until they rupture because of the nonspecific symptoms.
      Secondary to PDA, obstructive jaundice is however an extremely rare
      manifestation. A case of an 84-year-old man is reported here, who suffered from
      severe jaundice caused by a ruptured PDA associated with CAS. In addition, this
      review collects and organizes PDAs with jaundice by applying a MEDLINE search and
      discusses the pathogenesis and therapeutic options of these aneurysms leading to
      external compression over the bile duct. Consequently, the formation of PDA with
      obstructive jaundice is based on the specific anatomy of pancreaticoduodenal
      arcades. When there is a retroperitoneal mass around the head of the pancreas
      associated with unexpected jaundice, PDA should be considered, for which early
      aggressive therapy is required. The case report and literature review suggest
      that PDA associated with obstructive jaundice may be treated successfully by
      single transcatheter arterial embolization (TAE) without auxiliary biliary
      drainage, whether it ruptures or not.

PMID- 25769286
TI  - Production of bioactive ginsenosides Rh2 and Rg3 by metabolically engineered
      yeasts.
AB  - Ginsenosides Rh2 and Rg3 represent promising candidates for cancer prevention and
      therapy and have low toxicity. However, the concentrations of Rh2 and Rg3 are
      extremely low in the bioactive constituents (triterpene saponins) of ginseng.
      Despite the available heterologous biosynthesis of their aglycone
      (protopanaxadiol, PPD) in yeast, production of Rh2 and Rg3 by a synthetic biology
      approach was hindered by the absence of bioparts to glucosylate the C3 hydroxyl
      of PPD. In this study, two UDP-glycosyltransferases (UGTs) were cloned and
      identified from Panax ginseng. UGTPg45 selectively transfers a glucose moiety to
      the C3 hydroxyl of PPD and its ginsenosides. UGTPg29 selectively transfers a
      glucose moiety to the C3 glucose of Rh2 to form a 1-2-glycosidic bond. Based on
      the two UGTs and a yeast chassis to produce PPD, yeast cell factories were built
      to produce Rh2 and/or Rg3 from glucose. The turnover number (kcat) of UGTPg29 was
      more than 2500-fold that of UGTPg45, which might explain the higher Rg3 yield
      than that of Rh2 in the yeast cell factories. Building yeast cell factories to
      produce Rh2 or Rg3 from simple sugars by microbial fermentation provides an
      alternative approach to replace the traditional method of extracting ginsenosides
      from Panax plants. 

PMID- 25769285
TI  - Dendritic remodeling of hippocampal neurons is associated with altered NMDA
      receptor expression in alcohol dependent rats.
AB  - Prolonged alcohol exposure has been previously shown to impair the structure and
      function of the hippocampus, although the underlying structural and biochemical
      alterations contributing to these deleterious effects are unclear. Also unclear
      is whether these changes persist into prolonged periods of abstinence. Previous
      work from our lab utilizing a clinically relevant rodent model of alcohol
      consumption demonstrated that alcohol dependence (induced by chronic intermittent
      ethanol vapor exposure or CIE) decreases proliferation and survival of neural
      stem cells in the hippocampal subgranular zone and hippocampal neurogenesis in
      the dentate gyrus, implicating this region of the cortex as particularly
      sensitive to the toxic effects of prolonged ethanol exposure. For this study, we
      investigated seven weeks of CIE-induced morphological changes (dendritic
      complexity and dendritic spine density) of dentate gyrus (DG) granule cell
      neurons, CA3, and CA1 pyramidal neurons and the associated alterations in
      biochemical markers of synaptic plasticity and toxicity (NMDA receptors and PSD
      95) in the hippocampus in ethanol-experienced Wistar rats 3h (CIE) and 21days
      (protracted abstinence) after the last ethanol vapor exposure. CIE reduced
      dendritic arborization of DG neurons and this effect persisted into protracted
      abstinence. CIE enhanced dendritic arborization of pyramidal neurons and this
      effect did not persist into protracted abstinence. The architectural changes in
      dendrites did not correlate with alterations in dendritic spine density, however,
      they were associated with increases in the expression of pNR2B, total NR2B, and
      total NR2A immediately following CIE with expression levels returning to control
      levels in prolonged abstinence. Overall, these data provide the evidence that CIE
      produces profound changes in hippocampal structural plasticity and in molecular
      tools that maintain hippocampal structural plasticity, and these alterations may
      underlie cognitive dysfunction associated with alcohol dependence. In addition,
      the compensatory state concurrent with reduced plasticity during protracted
      abstinence could leave the hippocampus vulnerable to subsequent insult following
      chronic ethanol exposure. 

PMID- 25769287
TI  - Rational design of a synthetic Entner-Doudoroff pathway for improved and
      controllable NADPH regeneration.
AB  - NADPH is an essential cofactor for the biosynthesis of several high-value
      chemicals, including isoprenoids, fatty acid-based fuels, and biopolymers.
      Tunable control over all potentially rate-limiting steps, including the NADPH
      regeneration rate, is crucial to maximizing production titers. We have rationally
      engineered a synthetic version of the Entner-Doudoroff pathway from Zymomonas
      mobilis that increased the NADPH regeneration rate in Escherichia coli MG1655 by
      25-fold. To do this, we combined systematic design rules, biophysical models, and
      computational optimization to design synthetic bacterial operons expressing the 5
      enzyme pathway, while eliminating undesired genetic elements for maximum
      expression control. NADPH regeneration rates from genome-integrated pathways were
      estimated using a NADPH-binding fluorescent reporter and by the productivity of a
      NADPH-dependent terpenoid biosynthesis pathway. We designed and constructed
      improved pathway variants by employing the RBS Library Calculator to efficiently
      search the 5-dimensional enzyme expression space and by performing 40 cycles of
      MAGE for site-directed genome mutagenesis. 624 pathway variants were screened
      using a NADPH-dependent blue fluorescent protein, and 22 were further
      characterized to determine the relationship between enzyme expression levels and
      NADPH regeneration rates. The best variant exhibited 25-fold higher normalized
      mBFP levels when compared to wild-type strain. Combining the synthetic Entner
      Doudoroff pathway with an optimized terpenoid pathway further increased the
      terpenoid titer by 97%. 

PMID- 25769288
TI  - Metabolic engineering of Corynebacterium glutamicum ATCC13869 for L-valine
      production.
AB  - In this study, an L-valine-producing strain was developed from Corynebacterium
      glutamicum ATCC13869 through deletion of the three genes aceE, alaT and ilvA
      combined with the overexpression of six genes ilvB, ilvN, ilvC, lrp1, brnF and
      brnE. Overexpression of lrp1 alone increased L-valine production by 16-fold.
      Deletion of the aceE, alaT and ilvA increased L-valine production by 44-fold.
      Overexpression of the six genes ilvB, ilvN, ilvC, lrp1, brnE and brnF in the
      triple deletion mutant WCC003 further increased L-valine production. The strain
      WCC003/pJYW-4-ilvBNC1-lrp1-brnFE produced 243mM L-valine in flask cultivation and
      437mM (51g/L) L-valine in fed-batch fermentation and lacked detectable amino-acid
      byproduct such as l-alanine and l-isoleucine that are usually found in the
      fermentation of L-valine-producing C. glutamicum.

PMID- 25769289
TI  - Installing extra bicarbonate transporters in the cyanobacterium Synechocystis sp.
      PCC6803 enhances biomass production.
AB  - As a means to improve carbon uptake in the cyanobacterium Synechocystis sp.
      strain PCC6803, we engineered strains to contain additional inducible copies of
      the endogenous bicarbonate transporter BicA, an essential component of the CO2
      concentrating mechanism in cyanobacteria. When cultured under atmospheric CO2
      pressure, the strain expressing extra BicA transporters (BicA(+) strain) grew
      almost twice as fast and accumulated almost twice as much biomass as the control
      strain. When enriched with 0.5% or 5% CO2, the BicA(+) strain grew slower than
      the control but still showed a superior biomass production. Introducing a point
      mutation in the large C-terminal cytosolic domain of the inserted BicA, at a site
      implicated in allosteric regulation of transport activity, resulted in a strain
      (BicA(+)(T485G) strain) that exhibited pronounced cell aggregation and failed to
      grow at 5% CO2. However, the bicarbonate uptake capacity of the induced
      BicA(+)(T485G) was twice higher than for the wild-type strain. Metabolic
      analyses, including phenotyping by synchrotron-radiation Fourier transform
      Infrared spectromicroscopy, scanning electron microscopy, and lectin staining,
      suggest that the excess assimilated carbon in BicA(+) and BicA(+)(T485G) cells
      was directed into production of saccharide-rich exopolymeric substances. We
      propose that the increased capacity for CO2 uptake in the BicA(+) strain can be
      capitalized on by re-directing carbon flux from exopolymeric substances to other
      end products such as fuels or high-value chemicals. 

PMID- 25769290
TI  - SPG11 mutation in a Turkish familial hypobetalipoproteinemia family with
      hereditary spastic paraplegia.

PMID- 25769291
TI  - Evaluation of the impact of neutralizing antibodies on IFNbeta response.
AB  - IFNbeta therapeutic action depends on a sequence of biological steps: i) the
      interaction between interferon beta (IFNbeta) and its receptor (IFNAR) located at
      the cell surface of peripheral blood mononuclear cells; ii) activation of second
      messengers; iii) transcription of several genes containing specific ISRE regions
      (Interferon Stimulated Response Elements); and iv) synthesis of specific
      proteins. Although IFNbeta therapy has improved treatment options of patients
      with multiple sclerosis (MS), the long-term efficacy of IFNbetas can be
      compromised due to the development of neutralizing antibodies (NAbs). High titer
      NAbs develop in about 15% of patients; they abolish IFNbeta biological activity
      and consequently the therapeutic action of IFNbeta. Different IFNbeta
      preparations carry different risks of developing NAbs, ranging from 3 to 28%. The
      risk of inducing NAbs must be considered in the selection of treatment.
      Guidelines for NAbs testing and the therapeutic decision in case of NAbs
      positivity have been established. NAbs positivity predicts MRI and clinical
      activity. Precocious identification of Nabs-positive patients and switch to
      alternative treatments can improve the percentage of responders and allow a
      better allocation of relevant economical resources. 

PMID- 25769292
TI  - Local sustained-release delivery systems of the antibiofilm agent
      thiazolidinedione-8 for prevention of catheter-associated urinary tract
      infections.
AB  - Thiazolidinedione-8 (TZD-8) is an anti-quorum-sensing molecule that has the
      potential to effectively prevent catheter-associated urinary tract infections, a
      major healthcare challenge. Sustained-release drug-delivery systems can enhance
      drugs' therapeutic potential, by maintaining their therapeutic level and reducing
      their side effects. Varnishes for sustained release of TZD-8 based on
      ethylcellulose or ammonio methacrylate copolymer type A (Eudragit((r)) RL) were
      developed. The main factors affecting release rate were found to be film
      thickness and presence of a hydrophilic or swellable polymer in the matrix. The
      release mechanism of ethylcellulose-based systems matched the Higuchi model.
      Selected varnishes were retained on catheters for at least 8 days. Sustained
      release delivery systems of TZD-8 were active against Candida albicans biofilms.
      The present study demonstrates promising results en route to developing
      applications for the prevention of catheter-associated infections.

PMID- 25769293
TI  - Multiple withdrawals from single-use vials: a study on sterility.
AB  - BACKGROUND: Reutilization of single-use vials containing medical drugs is still
      under discussion. This practice has been adopted as a standard to avoid drug
      wastage, particularly in developing countries and in the aftermath of disasters.
      Some studies have assessed sterility of medications stored in single-use vials
      after utilization as multiple doses; however, most of these were limited to one
      single drug, included a low number of samples and did not consider an
      intermediate transfer step from the vial to a disposable syringe. The purpose of
      this study was to assess microbial contamination of samples withdrawn over three
      days from disposable syringes prepared from single-use vials. METHODS: A
      prospective sterility study was conducted. A total of 600 initial samples were
      prepared from six-hundred 10 mL single-use vials of physiological solution into
      six-hundred 20 mL disposable syringes. Samples were prepared in three different
      standard operating rooms, on six different days and by the same operator, using
      basic sterile technique. All syringes were capped, placed together in a non
      sterile steel container, covered with a clean drape and stored in the
      refrigerator at 4 degrees C under non-sterile conditions. Using basic sterile
      technique, four samples were withdrawn daily and cultured from each syringe over
      the next 3 days. Microbial growth was examined on Sabouraud agar and chocolate
      agar culture media. RESULTS: A total of 7200 samples were collected and 14,400
      cultures were performed. No evidence of microbial growth in any of the culture
      media plates was found. CONCLUSION: This study demonstrated that contents
      initially stored in single-use vials and subsequently transferred into disposable
      syringes in an operating room using sterile technique, maintain sterility after 4
      withdrawals per day for a total of 3 days.

PMID- 25769294
TI  - Nano-formulation of rifampicin with enhanced bioavailability: development,
      characterization and in-vivo safety.
AB  - Rifampicin (RIF) was encapsulated into solid lipid nanoparticles (SLNs) to
      overcome its poor and unreliable oral bioavailability. Novel microemulsification
      method with high drug loading (50%) and entrapment efficiency (~67%) was
      developed (Indian Patent Application 3356/DEL/2013). RIF-SLNs were characterized
      using TEM, AFM, DSC and XRD. Near neutral SLNs (zeta -3.5 +/- 0.8), with average
      particle size of 130.0 +/- 22.6 nm showed 70.12% release in phosphate buffer pH
      6.8 in 9 days. Single oral dose (50mg/kg) pharmacokinetic studies in Wistar rats
      indicated 8.14 times higher (in comparison to free RIF) plasma bioavailability
      with sustained levels for 5 days. Pharmacodynamic parameters viz. TMIC (120 h;
      time for which plasma levels were above MIC of 0.2 MUg/ml), AUC0-infinity/MIC
      (1868.9h) and Cmax/MIC (75.6) for RIF-SLNs were greater than free RIF by 2.5, 8.2
      and 6.6 times, respectively. Similar LD50 (1570 mg/kg) and absence (or reversal
      in satellite group) of adverse events in repeat dose (three doses; highest dose
      was up to 50 times the human therapeutic dose) toxicity studies confirmed safety
      of RIF-SLNs. Improved pharmacokinetic profile of RIF-SLNs can be translated to a
      reduced dose and dosage frequency of RIF, thus resulting in lower or no
      hepatotoxicity commonly associated with its use.

PMID- 25769295
TI  - Relationship between energy expenditure, physical activity and weight loss during
      CPAP treatment in obese OSA subjects.
AB  - BACKGROUND: Increased energy expenditure (EE) has been reported in patients with
      obstructive sleep apnea (OSA). It has been postulated that CPAP treatment may
      induce weight reduction in obese patients, even if it has not been confirmed by
      recent studies. In the present study we investigated the effect of OSA on EE and
      the effect of CPAP on body weight and physical activity. METHODS: One hundred and
      seven obese OSA patients and 25 healthy obese volunteers, as control group,
      matched for age, sex and BMI, were enrolled. The following evaluation was
      performed only in OSA patients after 6 months of CPAP treatment. RESULTS:
      Baseline total EE was similar in the two groups, but OSA patients showed higher
      EE during the night, while control group during daytime. In patients, EE
      correlates with OSA severity, degree of daytime sleepiness or obesity. At follow
      up evaluation, BMI and total EE were unchanged. However, daytime EE increased
      (1066 +/- 131.5 vs 1104 +/- 133 Kcal/die, p < 0.001, respectively) and night EE
      decreased (694 +/- 69 vs 595 +/- 73, p < 0.0001, respectively). Statistically
      significant changes in BMI, sleepiness scale, blood gases and EE were found only
      in patients who were compliant to CPAP. CONCLUSIONS: Obese OSA patients showed an
      increased night EE that was normalized only in those patients compliant to CPAP.
      Body weight and daily physical activity did not change in statistically
      significant way.

PMID- 25769296
TI  - Drug treatments for rheumatoid arthritis: looking backwards to move forwards.

PMID- 25769298
TI  - GPs to get 1% pay rise for 2015-16.

PMID- 25769297
TI  - Ca2+ Regulation of Trypanosoma brucei Phosphoinositide Phospholipase C.
AB  - We characterized a phosphoinositide phospholipase C (PI-PLC) from the procyclic
      form (PCF) of Trypanosoma brucei. The protein contains a domain organization
      characteristic of typical PI-PLCs, such as X and Y catalytic domains, an EF-hand
      calcium-binding motif, and a C2 domain, but it lacks a pleckstrin homology (PH)
      domain. In addition, the T. brucei PI-PLC (TbPI-PLC) contains an N-terminal
      myristoylation consensus sequence found only in trypanosomatid PI-PLCs. A peptide
      containing this N-terminal domain fused to green fluorescent protein (GFP) was
      targeted to the plasma membrane. TbPI-PLC enzymatic activity was stimulated by
      Ca(2+) concentrations below the cytosolic levels in the parasite, suggesting that
      the enzyme is constitutively active. TbPI-PLC hydrolyzes both
      phosphatidylinositol (PI) and phosphatidylinositol 4,5-bisphosphate (PIP2), with
      a higher affinity for PIP2. We found that modification of a single amino acid in
      the EF-hand motif greatly affected the protein's Ca(2+) sensitivity and substrate
      preference, demonstrating the role of this motif in Ca(2+) regulation of TbPI
      PLC. Endogenous TbPI-PLC localizes to intracellular vesicles and might be using
      an intracellular source of PIP2. Knockdown of TbPI-PLC expression by RNA
      interference (RNAi) did not result in growth inhibition, although enzymatic
      activity was still present in parasites, resulting in hydrolysis of PIP2 and a
      contribution to the inositol 1,4,5-trisphosphate (IP3)/diacylglycerol (DAG)
      pathway. 

PMID- 25769299
TI  - The Symbolic Value and Limitations of Racial Concordance in Minority Research
      Engagement.
AB  - The well-documented underrepresentation of racial and ethnic minorities in
      research demands action. The field of health disparities research, however, lacks
      scientific consensus about how best to respectfully recruit underrepresented
      minority populations in research. We explore the investigators' perspective
      regarding how their own racial and ethnic background influenced their ability to
      recruit minorities, including (a) the influence of racial concordance ("race
      matching") in research recruitment, (b) attributes and shared values important in
      the development of trust with minority communities, and (c) the role self
      reflection plays in the development of meaningful research relationships. In
      2010, we conducted in-depth, semi-structured, telephone interviews with
      investigators (N= 31) experienced with minority populations. Through the analysis
      of this coherent narrative, we uncovered both the symbolic and surface-level
      assumptions regarding minority recruitment to expose a deep structural
      understanding of race, ethnicity, and social context that is critical for
      bridging the true social difference between researchers and participants.

PMID- 25769301
TI  - Magnetic, fluorescent, and thermo-responsive poly(MMA-NIPAM-Tb(AA)3Phen)/Fe3O4
      multifunctional nanospheres prepared by emulsifier-free emulsion polymerization.
AB  - Magnetic, luminescent, and thermoresponsive multifunctional nanospheres composed
      of modified Fe3O4 nanoparticles as the core and rare earth complex Tb(AA)3Phen as
      the shell are synthesized by emulsifier-free emulsion polymerization. The core
      shell spherical structure has a size between 140 and 220 nm and exhibits strong
      green fluorescence of the rare earth complex Tb(AA)3Phen. In the R2 relaxivity
      and in vivo MRI studies, the R2 relaxivity of the nanospheres is 562.56 mM(-1) s(
      1) and enhanced T2-weighted images are observed from the nanospheres in the liver
      and spleen after injection as a contrast agent. The excellent superparamagnetic,
      thermosensitive, and fluorescent properties render the nanospheres useful in
      biomedical engineering and optical imaging.

PMID- 25769300
TI  - Ex vivo antibody-dependent cellular cytotoxicity inducibility predicts efficacy
      of cetuximab.
AB  - We conducted in vitro studies and a clinical trial for patients with squamous
      cell carcinoma of the head and neck (SCCHN) to study the relationship between
      FcgammaRIIIa polymorphisms and antibody-dependent cellular cytotoxicity (ADCC).
      In vitro, FcgammaRIIIa genotype was correlated with ADCC and innate cytotoxicity
      using natural killer (NK) cells harvested from healthy donors. In the phase II
      study, patients with recurrent or metastatic SCCHN were treated with cetuximab
      (500 mg/m(2) i.v. every 2 weeks) and lenalidomide (25 mg daily). FcgammaRIIIa
      genotype and ex vivo ADCC were correlated with clinical response, progression
      free survival (PFS), and overall survival (OS). In vitro, healthy donors with a
      FcgammaRIIIa 158-V allele demonstrated more effective ADCC against two colon
      cancer cell lines HT29 and SW480, mean cytotoxicity: FF 16.1%, VF/VV 24.3% (P =
      0.015) and FF 11.7%, VF/VV 21.0% (P = 0.008), respectively. We observed a linear
      relationship between ADCC response and innate cytotoxicity. In the phase II
      trial, 40 patients received cetuximab and lenalidomide with median PFS of 7.2
      weeks and OS of 16.4 weeks. Thirty-six patients had FcgammaRIIIa genotype: VV
      (2), VF (20), and FF (14), and 25 patients had sufficient NK-cell yield to
      perform ex vivo ADCC. FcgammaRIIIa genotype was not associated with any clinical
      outcomes. Patients mounting ex vivo ADCC response had a higher likelihood of
      stable disease (P = 0.01) and showed a trend toward increased PFS: 14 weeks
      versus 6.8 weeks, respectively (P = 0.13). Enhanced ex vivo ADCC and innate
      immunity responses were more predictive of clinical response than FcgammaRIIIa
      and may offer a functional assay to select patients suitable for cetuximab
      therapy.

PMID- 25769303
TI  - Switching from tenofovir to abacavir in HIV-1-infected patients with low bone
      mineral density: changes in bone turnover markers and circulating sclerostin
      levels.
AB  - BACKGROUND: Tenofovir is involved in accelerated bone mineral density (BMD) loss.
      METHODS: We recently published a hip BMD improvement at week 48 [+2.1% (95% CI: 
      0.6, 4.7) (P = 0.043)] in HIV-infected patients with osteopenia/osteoporosis
      randomized to switch from tenofovir to abacavir (n = 26), although without
      reaching statistical significance compared with those who maintained tenofovir (n
      = 28). Here, we present changes at week 48 in bone markers [C-terminal
      telopeptide of collagen type 1 (CTX), osteocalcin and procollagen type 1 N
      propeptide (P1NP)] as well as in circulating levels of three proteins involved in
      bone regulation [osteoprotegerin, receptor activator for NF-kappaB ligand (RANKL)
      and sclerostin, a selective regulator of bone formation through the Wnt pathway]
      in 44 of these patients. chi(2) or Fisher and Student t-tests were performed
      according to the distribution of the variables. RESULTS: Bone markers decreased
      only in the abacavir group [mean (SD) CTX changed from 0.543 (0.495) to 0.301
      (0.306) ng/mL; mean (SD) osteocalcin changed from 23.72 (22.20) to 13.95 (12.40)
      ng/mL; and mean (SD) P1NP changed from 54.68 (54.52) to 28.65 (27.48) ng/mL (P <
      0.001 in all cases)], reaching statistical significance between the groups at
      week 48. Osteoprotegerin did not vary, but sclerostin significantly increased in
      the abacavir group [from 29.53 (27.91) to 35.56 (34.59) pmol/L, P = 0.002]. No
      significant differences in osteoprotegerin and sclerostin were detected between
      the groups at week 48. RANKL values were below the limit of detection in all
      samples. CONCLUSIONS: The switch from tenofovir to abacavir seems to induce a
      positive effect on bone tissue, since bone turnover markers decreased. In
      addition, circulating sclerostin levels increased, a change associated with
      improved bone properties.

PMID- 25769304
TI  - The molecular basis of oligomeric organization of the human M3 muscarinic
      acetylcholine receptor.
AB  - G protein-coupled receptors, including the M3 muscarinic acetylcholine receptor,
      can form homo-oligomers. However, the basis of these interactions and the overall
      organizational structure of such oligomers are poorly understood. Combinations of
      site-directed mutagenesis and homogenous time-resolved fluorescence resonance
      energy transfer studies that assessed interactions between receptor protomers at
      the surface of transfected cells indicated important contributions of regions of
      transmembrane domains I, IV, V, VI, and VII as well as intracellular helix VIII
      to the overall organization. Molecular modeling studies based on both these
      results and an X-ray structure of the inactive state of the M3 receptor bound by
      the antagonist/inverse agonist tiotropium were then employed. The results could
      be accommodated fully by models in which a proportion of the cell surface M3
      receptor population is a tetramer with rhombic, but not linear, orientation. This
      is consistent with previous studies based on spectrally resolved, multiphoton
      fluorescence resonance energy transfer. Modeling studies furthermore suggest an
      important role for molecules of cholesterol at the dimer + dimer interface of the
      tetramer, which is consistent with the presence of cholesterol at key locations
      in many G protein-coupled receptor crystal structures. Mutants that displayed
      disrupted quaternary organization were often poorly expressed and showed immature
      N-glycosylation. Sustained treatment of cells expressing such mutants with the
      muscarinic receptor inverse agonist atropine increased cellular levels and
      restored both cell surface delivery and quaternary organization to many of the
      mutants. These observations suggest that organization as a tetramer may occur
      before plasma membrane delivery and may be a key step in cellular quality control
      assessment. 

PMID- 25769306
TI  - A vaccine study design selection framework for the postlicensure rapid
      immunization safety monitoring program.
AB  - The Postlicensure Rapid Immunization Safety Monitoring Program, the vaccination
      safety monitoring component of the US Food and Drug Administration's Mini
      Sentinel project, is currently the largest cohort in the US general population
      for vaccine safety surveillance. We developed a study design selection framework
      to provide a roadmap and description of methods that may be utilized to evaluate
      potential associations between vaccines and health outcomes of interest in the
      Postlicensure Rapid Immunization Safety Monitoring Program and other systems
      using administrative data. The strengths and weaknesses of designs for vaccine
      safety monitoring, including the cohort design, the case-centered design, the
      risk interval design, the case-control design, the self-controlled risk interval
      design, the self-controlled case series method, and the case-crossover design,
      are described and summarized in tabular form. A structured decision table is
      provided to aid in planning of future vaccine safety monitoring activities, and
      the data components comprising the structured decision table are delineated. The
      study design selection framework provides a starting point for planning vaccine
      safety evaluations using claims-based data sources.

PMID- 25769305
TI  - Cyclic Adenosine 3',5'-Monophosphate Elevation and Biological Signaling through a
      Secretin Family Gs-Coupled G Protein-Coupled Receptor Are Restricted to a Single
      Adenylate Cyclase Isoform.
AB  - PC12 cells express five adenylate cyclase (AC) isoforms, most abundantly AC6 and
      AC7. These two ACs were individually silenced using lentiviral short hairpin
      RNAs, which lead to a decrease (>=80%) of the protein product of each transcript.
      These stable PC12 sublines were then used to examine potential AC isoform
      preference for signaling through a family B G protein-coupled receptor (GPCR).
      Cells were challenged with the endogenous agonist of the pituitary adenylate
      cyclase-activating polypeptide type I receptor (PAC1), pituitary adenylate
      cyclase-activating polypeptide (PACAP)-38, or the diterpene forskolin as an AC
      proximal control. Intracellular cAMP levels were elevated by forskolin about
      equally in wild-type, AC6, and AC7 knockdown cells. The ability of PACAP-38 and
      forskolin to activate three cAMP sensors downstream of AC [protein kinase A
      (PKA), exchange protein activated by cAMP (Epac) 2/Rapgef4, and neuritogenic cAMP
      sensor (NCS)/Rapgef2] was examined by monitoring the phosphorylation status of
      their respective targets, cAMP response element-binding protein, p38, and
      extracellular signal-regulated kinase. Forskolin stimulation of each downstream
      target of cAMP was unaffected by knockdown of either AC6 or AC7. PACAP-38
      activation of all downstream targets of cAMP was unaffected by AC7 knockdown, but
      abolished following AC6 knockdown. Membrane cholesterol depletion with methyl
      beta-cyclodextrin mimicked the effects of AC6 silencing on PACAP signaling,
      without attenuating forskolin signaling. These data suggest that vicinal
      constraint of the GPCR PAC1 and AC6 determines the exclusive requirement for this
      AC in PACAP signaling, but that the coupling of the cAMP sensors PKA,
      Epac2/Rapgef4, and NCS/Rapgef2, to their respective downstream signaling targets,
      determines how cAMP signaling is parcellated to physiologic responses, such as
      neuritogenesis, upon GPCR-Gs activation in neuroendocrine cells. 

PMID- 25769307
TI  - Incidence and Predictors of HIV and Sexually Transmitted Infections Among Female
      Sex Workers and Their Intimate Male Partners in Northern Mexico: A Longitudinal,
      Multilevel Study.
AB  - Preventing human immunodeficiency virus (HIV) infection and other sexually
      transmitted infections (STIs) requires an understanding of sexual relationship
      factors beyond the individual level. We estimated HIV/STI incidence and
      identified time-varying predictors of STI acquisition in a prospective cohort
      study of female sex workers and their intimate (noncommercial) male partners in
      northern Mexico. From 2010 to 2013, couples underwent behavioral and biological
      assessments biannually for 24 months. Among 413 initially HIV-uninfected
      participants, 8 seroconverted during follow-up. Incidence of HIV (1.12 cases/100
      person-years (PY)), chlamydia (9.47 cases/100 PY), active syphilis (4.01
      cases/100 PY), and gonorrhea (1.78 cases/100 PY) was higher among women than
      among men (HIV: P = 0.069; all STIs combined: P < 0.001). In multivariable
      conditional logistic regression with individual fixed effects and correlated
      error terms within couples, risk of STI acquisition was significantly higher
      among women who had recently used cocaine, crack, or methamphetamine (adjusted
      odds ratio (OR) = 2.13, 95% confidence interval (CI): 1.07, 4.28). STI risk was
      lower among women who reported physically assaulting their male partners
      (adjusted OR = 0.44, 95% CI: 0.22, 0.86) and among men whose female partners had
      regular sex-work clients (adjusted OR = 0.38, 95% CI: 0.14, 1.03). Improving
      vulnerable couples' sexual health will require addressing the contexts in which
      drug use, interpersonal conflict, and economic vulnerability converge. 

PMID- 25769308
TI  - Endomembrane proteomics reveals putative enzymes involved in cell wall metabolism
      in wheat grain outer layers.
AB  - Cereal grain outer layers fulfil essential functions for the developing seed such
      as supplying energy and providing protection. In the food industry, the grain
      outer layers called 'the bran' is valuable since it is rich in dietary fibre and
      other beneficial nutriments. The outer layers comprise several tissues with a
      high content in cell wall material. The cell wall composition of the grain
      peripheral tissues was investigated with specific probes at a stage of active
      cell wall synthesis. Considerable wall diversity between cell types was revealed.
      To identify the cellular machinery involved in cell wall synthesis, a subcellular
      proteomic approach was used targeting the Golgi apparatus where most cell wall
      polysaccharides are synthesized. The tissues were dissected into outer pericarp
      and intermediate layers where 822 and 1304 proteins were identified respectively.
      Many carbohydrate-active enzymes were revealed: some in the two peripheral grain
      fractions, others only in one tissue. Several protein families specific to one
      fraction and with characterized homologs in other species might be related to the
      specific detection of a polysaccharide in a particular cell layer. This report
      provides new information on grain cell walls and its biosynthesis in the valuable
      outer tissues, which are poorly studied so far. A better understanding of the
      mechanisms controlling cell wall composition could help to improve several
      quality traits of cereal products (e.g. dietary fibre content, biomass conversion
      to biofuel). 

PMID- 25769309
TI  - qRT9, a quantitative trait locus controlling root thickness and root length in
      upland rice.
AB  - Breeding for strong root systems is an important strategy for improving drought
      avoidance in rice. To clone genes responsible for strong root traits, an upland
      rice introgression line IL392 with thicker and longer roots than the background
      parent lowland rice Yuefu was selected. A quantitative trait locus (QTL), qRT9,
      controlling root thickness and root length was detected under hydroponic culture
      using 203 F(2:3) populations derived from a cross between Yuefu and IL392. The
      qRT9 locus explained 32.5% and 28.1% of the variance for root thickness and root
      length, respectively. Using 3185 F2 plants, qRT9 was ultimately narrowed down to
      an 11.5 kb region by substitution mapping. One putative basic helix-loop-helix
      (bHLH) transcription factor gene, LOC_Os09g28210 (named OsbHLH120), is annotated
      in this region. Sequences of OsbHLH120 in 11 upland rice and 13 lowland rice
      indicated that a single nucleotide polymorphism (SNP) at position 82 and an
      insertion/deletion (Indel) at position 628-642 cause amino acid changes and are
      conserved between upland rice and lowland rice. Phenotypic analysis indicated
      that the two polymorphisms were significantly associated with root thickness and
      root length under hydroponic culture. Quantitative real-time PCR showed that
      OsbHLH120 was strongly induced by polyethylene glycol (PEG), salt, and abscisic
      acid, but higher expression was present in IL392 roots than in Yuefu under PEG
      and salt stress. The successfully isolated locus, qRT9, enriches our knowledge of
      the genetic basis for drought avoidance and provides an opportunity for breeding
      drought avoidance varieties by utilizing valuable genes in the upland rice
      germplasm.

PMID- 25769310
TI  - "You can't be cold and scientific": community views on ethical issues in
      intellectual disability research.
AB  - Perceptions, attitudes, and ethical concerns related to conducting research with
      adults with intellectual disability hinder scientific innovation to promote
      health. Yet we lack an understanding of community views on effective research
      policy and practice. To address this knowledge void, we qualitatively studied the
      views of adults with intellectual disability and those who provide them support
      regarding research participation of adults with intellectual disability. We found
      substantial support for their inclusion, particularly given the possibility of
      benefits to adults with intellectual disability, researchers, and society. We
      also found concerns for potential harm and differing ideas on how to promote
      safety. Our findings emphasize the importance of their inclusion in research, and
      the need for policies and practices that promote respect and safety. 

PMID- 25769311
TI  - Predictors of parental consent for adolescent participation in sexual health
      related research.
AB  - The purpose of the present study was to describe the degree to which parents of
      adolescents were willing to grant consent for their teenagers' participation in
      sexually themed research, and to link the likelihood of consent to parents'
      demographics, personality traits, parenting, attitudes, and their children's
      characteristics. A total of 203 parents of adolescents ages 13 to 18 years
      anonymously responded to an internet survey (81.7% mothers; 87% European
      American). Approximately 40% of respondents were possibly willing and 36% were
      definitely willing to provide consent for a hypothetical study covering all
      included sexual health topics. Parents were more likely to give consent if they
      were highly extraverted, viewed science positively, were not highly conservative
      about sexuality, and if they thought their teenager was already sexually
      experienced. Overall, many parents appear to be quite open to adolescent survey
      participation. 

PMID- 25769312
TI  - Mirror me: Imitative responses in adults with autism.
AB  - Dysfunctions of the human mirror neuron system have been postulated to underlie
      some deficits in autism spectrum disorders including poor imitative performance
      and impaired social skills. Using three reaction time experiments addressing
      mirror neuron system functions under simple and complex conditions, we examined
      20 adult autism spectrum disorder participants and 20 healthy controls matched
      for age, gender and education. Participants performed simple finger-lifting
      movements in response to (1) biological finger and non-biological dot movement
      stimuli, (2) acoustic stimuli and (3) combined visual-acoustic stimuli with
      different contextual (compatible/incompatible) and temporal
      (simultaneous/asynchronous) relation. Mixed model analyses revealed slower
      reaction times in autism spectrum disorder. Both groups responded faster to
      biological compared to non-biological stimuli (Experiment 1) implying intact
      processing advantage for biological stimuli in autism spectrum disorder. In
      Experiment 3, both groups had similar 'interference effects' when stimuli were
      presented simultaneously. However, autism spectrum disorder participants had
      abnormally slow responses particularly when incompatible stimuli were presented
      consecutively. Our results suggest imitative control deficits rather than global
      imitative system impairments. 

PMID- 25769313
TI  - Attentional allocation of autism spectrum disorder individuals: Searching for a
      Face-in-the-Crowd.
AB  - A study is reported which tests the proposition that faces capture the attention
      of those with autism spectrum disorders less than a typical population. A visual
      search task based on the Face-in-the-Crowd paradigm was used to examine the
      attentional allocation of autism spectrum disorder adults for faces. Participants
      were required to search for discrepant target images from within 9-image arrays.
      Both participants with autism spectrum disorder and control participants
      demonstrated speeded identification of faces compared to non-face objects. This
      indicates that when attention is under conscious control, both autism spectrum
      disorder and typically developing comparison adults show an attentional bias for
      faces, which contrasts with previous research which found an absence of an
      attentional bias for faces in autism spectrum disorder. Theoretical implications
      of this differentiation are discussed. 

PMID- 25769315
TI  - Mechanism of programmed cell death factor 4/nuclear factor-kappaB signaling
      pathway in porcine coronary micro-embolization-induced cardiac dysfunction.
AB  - The aim of this study was to investigate the role of the programmed cell death
      factor 4 (PDCD4)/nuclear factor-kappaB (NF-kappaB) signaling pathway in coronary
      micro-embolism (CME)-induced inflammatory responses and cardiac dysfunction in a
      porcine model. Bama miniature pigs were randomly divided into four groups (n = 5
      per group). Micro-embolization balls or saline were infused through a
      microcatheter in the left anterior descending (LAD) artery in the CME and Sham
      groups, respectively. PDCD4 siRNA or control siRNA mixed with transfection
      reagent was infused via the LAD artery 72 h before CME induction in the CME +
      siRNA-PDCD4 and siRNA-control groups, respectively. Cardiac function was
      evaluated with ultrasound. Tissue biopsy was stained with hematoxylin-eosin (HE)
      and hematoxylin basic fuchsin picric acid (HBFP) to measure infarction area.
      Myocardial PDCD4 and tumor necrosis factor-alpha (TNF-alpha) mRNA and protein
      expression were analyzed by quantitative PCR and Western blotting. NF-kappaB
      activity was evaluated in gel electrophoretic mobility shift assay.
      Echocardiographic parameters showed that compared with the sham group, the CME
      group had impaired heart function, manifested as systolic dysfunction and left
      ventricular dilatation (reduced left ventricular ejection fraction [LVEF], left
      ventricular fractional shortening [FS], and cardiac output [CO] [P < 0.05] and
      increased left ventricular end-diastolic diameter [LVEDd] [P < 0.05]). Compared
      with the CME group, the CME + siRNA-PDCD4 group had attenuated CME-induced
      cardiac function damage (increased LVEF, FS and CO [P < 0.05] and reduced LVEDd
      [P < 0.05]). Compared with the sham group, the CME group had significantly
      increased PDCD4 and TNF-alpha mRNA and protein expression and increased NF-kappaB
      activity (P < 0.05). These effects were significantly inhibited in the CME +
      siRNA-PDCD4 group (P < 0.05). In conclusion, PDCD4/NF-kappaB signaling pathway
      activation is an important mechanism for CME-induced cardiac dysfunction,
      suggesting that inhibition of PDCD4/NF-kappaB signaling pathway may be a
      potential target for the prevention and treatment of CME.

PMID- 25769314
TI  - Parkinson's disease and enhanced inflammatory response.
AB  - Parkinson's disease (PD) is the first and second most prevalent motor and
      neurodegenerative disease, respectively. The clinical symptoms of PD result from
      a loss of midbrain dopaminergic (DA) neurons. However, the molecular cause of DA
      neuron loss remains elusive. Mounting evidence implicates enhanced inflammatory
      response in the development and progression of PD pathology. This review examines
      current research connecting PD and inflammatory response. 

PMID- 25769317
TI  - Large-scale micro- and nanopatterns of Cu(In,Ga)Se2 thin film solar cells by mold
      assisted chemical-etching process.
AB  - A reactive mold-assisted chemical etching (MACE) process through an easy-to-make
      agarose stamp soaked in bromine methanol etchant to rapidly imprint larger area
      micro- and nanoarrays on CIGS substrates was demonstrated. Interestingly, by
      using the agarose stamp during the MACE process with and without additive
      containing oil and triton, CIGS microdome and microhole arrays can be formed on
      the CIGS substrate. Detailed formation mechanisms of microstructures and the
      chemical composition variation after the etching process were investigated. In
      addition, various microand nanostructures were also demonstrated by this
      universal approach. The microstructure arrays integrated into standard CIGS solar
      cells with thinner thickness can still achieve an efficiency of 11.22%, yielding
      an enhanced efficiency of ~18% compared with that of their planar counterpart due
      to an excellent absorption behavior confirmed by the simulation results, which
      opens up a promising way for the realization of high-efficiency micro- or
      nanostructured thin-film solar cells. Finally, the complete dissolution of
      agarose stamp into hot water demonstrates an environmentally friendly method by
      the mold-assisted chemical etching process through an easy-to-make agarose stamp.

PMID- 25769316
TI  - The 1,2,3-triazole derivative KP-A021 suppresses osteoclast differentiation and
      function by inhibiting RANKL-mediated MEK-ERK signaling pathway.
AB  - The triazole family of compounds has been implicated in modulating various
      biological processes such as inflammation, tumorigenesis, and infection. To our
      knowledge, this is the first study to demonstrate the effects of 1,2,3-triazole
      substituted biarylacrylonitrile compounds, including KP-A021, on the
      differentiation and function of osteoclasts. KP-A021 and its triazole
      derivatives, at a concentration that does not cause a cytotoxic response in bone
      marrow macrophages (BMMs), significantly inhibited osteoclast differentiation
      induced by receptor activator of nuclear factor-kappaB ligand (RANKL) and
      macrophage colony-stimulating factor (M-CSF) as assessed by tartrate-resistant
      acid phosphatase (TRAP) staining. KP-A021 also dramatically inhibited the
      expression of marker genes associated with osteoclast differentiation, such as
      TRAP, cathepsin K (Cat K), dendritic cell-specific transmembrane protein (DC
      STAMP), and nuclear factor of activated T-cells, cytoplasmic 1 (NFATc1).
      Furthermore, KP-A021 inhibited actin ring formation in osteoclasts as well as
      resorption pit formation induced by osteoclasts. Analysis of the signaling
      pathway for KP-A021 indicated that this triazole compound inhibited the RANKL
      induced activation of extracellular signal-regulated kinase (ERK) and its
      upstream signaling molecule, mitogen-activated protein kinase kinase1/2 (MEK1/2).
      Taken together, these results demonstrate that KP-A021 has an inhibitory effect
      on the differentiation and function of osteoclasts via modulation of the RANKL
      induced activation of the MEK-ERK pathway. 

PMID- 25769318
TI  - MRI manifestation of xanthomatous hypophysitis: a case report and review of the
      literature.
AB  - The inflammatory lesion of the pituitary gland is unusual. A 33-year-old woman
      with headache, visual impairment, and menelipsis was admitted to the Second
      Xiangya Hospital, Central South University. The results of magnetic resonance
      imaging (MRI) for pituitary gland showed a sellar mass with iso-intensity on T1
      weighted imaging and high signal on T2 weighted imaging. The homogeneous lesion
      was enhanced on contrast MRI. The pituitary stalk was thickened accompanied by
      the cavernous sinus invasion, which showed a "triangle" saddle occupation on the
      MRI coronal plane. An endocrinological examination revealed mild hypocortisolism.
      Th e patient was diagnosed as pituitary adenoma based on the MRI findings and
      endocrinological examination. Trans-sphenoidal surgery was performed. The intra
      operative histological examination also suggested a pituitary adenoma. Th e
      histopathological examination showed accumulation of foamy cells and xanthomatous
      epithelioid cells, supporting the diagnosis of xanthomatous hypophysitis.
      Xanthomatous hypophysitis possesses certain MRI features. Th e most typical
      imaging features are the thickening of the pituitary stalk and the sign of
      "triangle" occupation on MRI coronal plane, which are very helpful to the correct
      diagnosis and optimal management.

PMID- 25769319
TI  - [A randomized, double-blind, controlled study: Ji-Tai tablet for the treatment of
      acute withdrawl syndrome of mild heroin dependence].
AB  - OBJECTIVE: To investigate the efficacy and safety of Ji-Tai tablet and Ji-Tai
      tablet combined with buprenorphine in the treatment of patients with acute
      withdrawal syndrome of mild heroin dependence. METHODS: A total of 150 patients
      with mild heroin dependence were recruited, and were randomly assigned to a Ji
      Tai tablet group (n=50), a Ji-Tai tablet combined with buprenorphine group (n=50)
      and a control group (n=50) during a 10-day clinical trial. Opiate withdrawal
      scale (OWS) was used to measure the severity of withdrawal symptoms. Anxiety
      symptoms assessments were made at 0 day (baseline), the day 5 (middle), and the
      day 10 (end) by the Hamilton anxiety scale (HAMA). Symptoms were assessed before
      and 1 h or 2 h after medication each day. The total withdrawal symptoms scores
      and the daily reduction rate were used to measure the effect of Ji-Tai tablet vs
      Ji- Tai tablet plus buprenorphine. Safety evaluation was carried out by the
      following measures: baseline of treatment, drug side effects after the treatment,
      vital signs (blood pressure, heart rate, and respiration rate), laboratory
      examination (routine blood and urine tests and the liver and kidney function
      tests), and electrocardiograms. RESULTS: A total of 142 mild heroin dependence
      patients performed the experiments (including 48 in the Ji-Tai tablet group, 48
      in the Ji-Tai tablet with buprenorphine group and 46 in the control group). The
      scores of baseline withdrawal symptoms were 43.520+/-19.786, 42.640+/-17.648 and
      47.100+/-24.450, respectively, with no significant differences among the 3 groups
      (all P>0.05 ). During the 10-day treatment, the reduction rate of acute
      withdrawal symptoms scores increased daily, the acute withdrawal syndrome scores
      and the anxiety symptoms scores declined from day 0 to day 10, there was also no
      significant difference among the 3 groups (all P>0.05). Ji-Tai tablet did not
      affect vital signs such as blood pressure, heart rate, and respiration rate.
      CONCLUSION: Ji-Tai tablet or Ji-Tai tablet combined with buprenorphine had no
      effect on acute withdrawal symptoms of mild heroin dependence.

PMID- 25769320
TI  - [Brain structure analysis for patients with antisocial personality disorder by
      MRI].
AB  - OBJECTIVE: To investigate the structural abnormalities of brain in patients with
      antisocial personality disorder (ASPD) but without alcoholism and drug abuse.
      METHODS: Volunteers from Hunan Reformatory (n=36) and the matched healthy
      subjects (n=26) were examined by high-spatial resolution magnetic resonance
      imaging (MRI) and diffusion tensor imaging (DTI). Voxel-based morphometry and
      fractional anisotropy (FA) maps were generated for each subject to reveal
      structural abnormalities in patients with ASPD. RESULTS: Compared with the
      healthy controls, ASPD patients showed significantly higher gray matter volumes
      in the inferior parietal lobule (P<=0.001, uncorrected), white matter volumes in
      the precuneus (P<=0.001, uncorrected), FA in the left lingual gyrus, bilateral
      precuneus, right superior frontal gyrus and right middle temporal gyrus (P<=0.01,
      uncorrected). CONCLUSION: Our results revealed the abnormal neuroanatomical
      features in ASPD patients, which might be related to the external behavioral
      traits in ASPD patients.

PMID- 25769321
TI  - [Effect of Pinggan Qianyang recipe on the expression of Tpx II HSP27 and ANXA1 in
      the hypothalamus of spontaneously hypertensive rats with hyperactivity of liver
      YANG syndrome].
AB  - OBJECTIVE: To investigate the effect Pinggan Qianyang recipe on expression of
      Tpx, HSP27 and ANXA1 in the hypothalamus of spontaneously hypertensive rats
      (SHRs) with the hyperactivity of liver-YANG syndrome. METHODS: A total of 30 SHRs
      were subjected to administration of Aconiti Praeparatae Decoction to establish
      the model of SHR with liver-YANG hyperactivity first, then they were randomly
      divided into three groups: the control group, the model group and the treatment
      group (n=10 per group). A total of 10 SD rats were served as the normal group.
      The rats in control group and treatment group were given Enalapril plus Pinggan
      Qianyang recipe for four weeks. The change of behavior and blood pressure of rats
      were monitored. RT-PCR and Western-blot were performed to detect the expression
      of Tpx II, HSP27 and ANXA1 mRNA and protein in the hypothalamus, respectively.
      RESULTS: Compared with the normal SD rats, the heart rate, blood pressure and
      grade of irritability were significantly increased while rotation endurance time
      was dramatically reduced in the SHR model with liver-YANG hyperactivity (P<0.01),
      these changes were reversed by the application of Enalapril plus Pinggan Qianyang
      recipe. Compared with the normal SD rats, the protein and mRNA expression of Tpx
      II and ANXA1 in the model group were significantly upregulated (P<0.01) while the
      HSP27 was significantly downregulated (P<0.01). Compared with the model group,
      the protein and mRNA expression of Tpx II and ANXA1 in the control group or
      treatment group were significantly decreased (P<0.05 or P<0.01) while HSP27 was
      significantly increased (P<0.05 or P<0.01). Compared with the control group, the
      expression of Tpx II and ANXA1 protein in treatment group were significantly
      reduced (P<0.05 or P<0.01). CONCLUSION: Pinggan Qianyang recipe can improve the
      blood pressure and behavior in SHRs with hyperactivity of Liver-YANG syndrome,
      which might be related to the regulation of Tpx, HSP27 and ANXA1 expression in
      hypothalamuses.

PMID- 25769322
TI  - [Pulchinenoside inhibits the fibroblast-like synoviocytes apoptosis in adjuvant
      arthritis rats].
AB  - OBJECTIVE: To explore the eff ect of pulchinenoside (PULC) on fi broblast-like
      synoviocytes (FLS) apoptosis in adjuvant arthritis (AA) rats. METHODS: A total of
      60 SD rats were randomly divided into 8 groups: A normal control group, an AA
      group, a low PULC group (50 mg/kg), a middle PULC group (100 mg/kg) or a high
      PULC group (150 mg/kg) and an ibuprofen (8 mg/kg) group (n=10 per group). FLS
      from the AA rats was cultured. The expression of Bcl-2, Bax, caspase-3 and the
      FLS proliferation were detected by the real time qPCR and MTT, respectively. The
      expression of IL-6 and IL-8 in culture medium was detected by ELISA. RESULTS:
      Compared with the AA group, the Bcl-2 expression was down-regulated (all P<0.05),
      the Bax and caspase-3 expression was up-regulated (all P<0.05), and the FLS
      proliferation was inhibited (all P<0.05). The IL-6 and IL-8 expression was
      suppressed in the FLS in the PULC groups at different dosages (all P<0.05) as
      well as in the ibuprofen group (P<0.05). CONCLUSION: PULC may inhibit the FLS
      proliferation in AA rats by increase in FLS apoptosis.

PMID- 25769323
TI  - [Effect of astragaloside on TL1A expression in viral myocarditis].
AB  - OBJECTIVE: Astragaloside is a simple substance of saponin and the active
      constituent of astragali. It was reported that the astragaloside exerted
      therapeutical eff ect on viral myocarditis and dilated cardiomyopathy. The
      purpose of this study was to investigate the effect of astragaloside on TL1A
      expression in viral myocarditis. METHODS: A total of 100 BALB/c mice were
      randomly divided into 6 groups: the normal control group (group A, n=10), the
      high-dose control group (group B, n=10), the myocarditis control group (group C,
      n=20), the low-dose group (group D, n=20), the middle-dose group (group E, n=20)
      and the high-dose group (group F, n=20). Mice in group A and group B were
      injected intraperitoneally with 0.1 mL EMEM solution, while mice in group C, D, E
      and F were treated with 0.1 mL of 1*102 TCID50 CVB3 (diluted in EMEM). Then, mice
      in group A and group B were treated with carboxymethycellulose solution and 9%
      astragaloside for 1 week, respectively. At the same time, mice in group C, D, E
      and F were treated with sodium carboxymethycellulose solution, 1% [0.07
      g/(kg.d)], 3% [0.2 g/(kg.d)] and 9%[0.6 g/(kg.d)] astragaloside for 1 week,
      respectively. After 14 days, the mice were sacrificed and their hearts were
      collected. The expression levels of TL1A mRNA and protein in the myocardium were
      examined by RT-PCR and immunohistochemistry, respectively. RESULTS: There was no
      death in the group A and B. The mortality in the group C, D, E and F was 45%
      (9/20), 30% (6/20), 25% (5/20) and 10% (2/20), respectively. Compared with the
      group C, the mortality in the group F was significantly decreased (P<0.05), but
      there no significant difference in mortality between the group C and the group D
      or E (P>0.05). There was no any pathological lesion in the group A and B. The
      TL1A mRNA and protein expression in the myocardium of mice in the group A and B
      was at low level, with no difference between them (P>0.05). Compared with the
      group A, the expression levels of TL1A mRNA and protein in the group C were
      markedly up-regulated (P<0.01), which was dramatically attenuated by the
      intervention of astragaloside at high dosage (the group F, P<0.01) but not at low
      (the group D) or middle-dosage (the group E) (P>0.05). CONCLUSION: Astragaloside
      may play a pivotal role in protection of the heart injury in viral myocarditis by
      suppressing the expression of TL1A.

PMID- 25769324
TI  - [Effect of depsides salts from Salvia miltiorrhiza on human hepatoma cell line
      SMMC-7721 subcutaneous xenografts in nude mice].
AB  - OBJECTIVE: To exlpore the eff ect of depsides salts from Salvia miltiorrhiza on
      human hepatoma cell line SMMC-7721 xenograft tumors and the possible mechanisms.
      METHODS: A total of 36 nude mice were divided into 6 groups: A model group, a
      negative control group, a positive control group, and 3 treatment groups at low,
      middle or high dose (n=6). The tumor model of nude mice was given depsides salts
      at a dose of 10, 20 or 50 mg/kg every 3 day for 16 days. Then samples of
      subcutaneous tumors in nude mice were collected. The morphological changes of
      tumor samples were observed by HE staining and the expression of vascular
      endothelial growth factor (VEGF) and the tumor antigen Ki67 was detected by
      immunohistochemical method. RESULTS: The tumor growth was inhibited by all doses
      of depsides salts. The morphology of tumors was shrinkage, broken and irregularly
      arranged compared with the tumors in the model group and the negative control
      group. Morphological changes were more obvious in tumors with treatment at high
      dose. Expression of VEGF and Ki67 in treatment groups and the positive control
      group were lower than that in the model group and the negative control group,
      with a significant difference (P<0.05). CONCLUSION: Depsides salts from Salvia
      miltiorrhiza can inhibit the growth of human hepatoma cell line SMMC-7721 tumor
      in nude mice, which is related to the inhibition of Ki67 and VEGF.

PMID- 25769325
TI  - [Protective effect of silibinin on islet beta cells in C57BL/6J mice fed a
      highfat diet].
AB  - OBJECTIVE: To explore the eff ect of silibinin on beta cells in C57BL/6J mice fed
      a high-fat diet and the possible mechanisms. METHODS: A total of 18 male C57BL/6J
      mice at 3 weeks old were divided into a normal chow group (n=6), a high-fat diet
      group (n=6) and a high-fat diet plus silibinin group (n=6). Aft er intervention
      for 10 weeks, fasting blood glucose (FBG), fasting insulin (FINS), triglycerides
      (TG), alanine aminotransferase (ALT), creatinine (Cr) and blood urea nitrogen
      (BUN), lipid metabolism, antioxidant enzyme activities and apoptosis were
      evaluated. Pancreatic tissues were isolated to examine insulin-induced gene-1
      (Insig-1), sterol regulatory element binding protein-1c (SREBP-1c) and fatty acid
      synthetase (FAS) mRNA and protein expression. RESULTS: Compared with the high-fat
      diet group, the function of insulin secretion was improved, and the level of
      blood glucose was decreased in the high-fat diet plus silibinin group (P<0.05).
      The levels of lipid content and oxidative stress and the rates of beta cell
      apoptosis were lower in high-fat diet plus silibinin group than those in the high
      fat diet group (both P<0.05). Simultaneously, the silibinin could promote the
      expression of Insig-1 and depress the expression of SREBP-1c and FAS (all
      P<0.05). Moreover, there was no significant difference in the levels of serum
      ALT, Cr and BUN among the 3 groups (all P>0.05). CONCLUSION: Silibinin can
      protect beta cells of mice fed a high-fat diet, and this effect might be related
      to, at least partially, increase in its antioxidative ability through regulation
      of insig-1/SREBP-1c pathway. Moreover, silibinin is safe for long-term treatment.

PMID- 25769326
TI  - [Plasma heparin cofactor II activity correlates with the incidence of in-stent
      restenosis after the intervention of arteriosclerosis obliterans in lower
      extremity].
AB  - OBJECTIVE: To explore the relationship between activity of plasma heparin
      cofactor II (HC II) and the incidence of in-stent restenosis aft er the
      intervention of arteriosclerosis obliterans in lower extremity. METHODS: A total
      of 62 patients with arteriosclerosis obliterans in lower extremity underwent
      femoropopliteal stent implantation. They were divided into 2 groups: A high HC II
      activity group (>=100%, n=40) and a low HC II activity group (<100%, n=22). All
      patients filled in follow up tables and conducted body examination. Possible risk
      factors resulting in restenosis were collected. Patients were followed up for 6
      months after femoropopliteal stent implantation. RESULTS: Baseline clinical
      characteristics were not significantly different between the 2 groups. The degree
      and incidence of angiographic restenosis at the end of the 6th month after the
      implantation in the high HC II activity group were all significantly lower than
      those in the low HC II activity group (P<0.05). Multivariate analysis
      demonstrated that high plasma HC II activity was an independent factor in
      reducing the incidence of angiographic restenosis (OR=0.982, P=0.048, 95%CI,
      0.966, 0.998). CONCLUSION: High plasma HC II activity is an independent factor in
      reducing the degree of in-stent restenosis. The lower the plasma HC II activity,
      the severer the degree of in-stent restenosis.

PMID- 25769327
TI  - [Localization of the assessment of chronic illness care and item evaluation].
AB  - OBJECTIVE: To translate the English version of the assessment of chronic illness
      care (ACIC) to Chinese, to conduct a trial in Hunan province and to develop a
      Chinese version ACIC. METHODS: According to the WHO rules, we translated the
      English version of the ACIC to Chinese and took the culture factor into account.
      Three hundred and ninety persons, who engaged in the work of chronic disease
      management in primary medical and health services in Hunan province, were
      enrolled for this study. One hundred and eighty three valid questionnaires were
      randomly selected. Six methods including discrete tendency method, good-poor
      analysis, correlation analysis, stepwise regression analysis, Cronbach's alpha
      coefficient and factor analysis were used for evaluation the questionnaire items.
      RESULTS: The items in Chinese version ACIC showed as follows: 1) good
      sensitivity. The standard deviation of each item was more than 2 and the P value
      from the t test between the good and poor group was less than 0.001; 2) good
      representation. The correlation coefficients range of each item with the total
      score and each dimension score was 0.588-0.916; 3) high internal consistency.
      Cronbach's alpha coefficient for the total scale was 0.975, and for each
      dimension range was 0.854-0.936; 4) independent. Factor loadings were greater
      than 0.40 entries, and factor loadings ranged from 0.487-0.798; 5) importance.
      Stepwise regression analysis alpha(in)=0.01, alpha(out)=0.05) showed 34 items
      were kept in the equation. CONCLUSION: Items of Chinese version ACIC retains ACIC
      7 dimensions of 34 items in the original English version, which are sensitivity
      and typical with the internal consistency, independence and importance.

PMID- 25769328
TI  - [Toll-like receptors and non-resolving inflammation-related cancer].
AB  - Toll-like receptors (TLRs) is a type of pattern recognition receptors (PRRs),
      which are singular, non-catalytic and highly homologous. TLRs not only play
      significant roles in natural immunity, but also act as a bridge between innate
      immunity and adaptive immunity. Recent studies have revealed that TLRs play
      critical roles in the development of non-resolving inflammation-related
      cancer,including the formation of tumor microenvironment, invasion and
      metastasis, immune escape, etc. Further investigation into the mechanisms
      responsible for the function of TLRs will be of great value in tumor prevention,
      early diagnosis and therapy.

PMID- 25769329
TI  - [Effect and mechanism of fluorofenidone on organ fibrosis].
AB  - Fibrosis can occur in different organs with high incidence rate and great danger.
      It still lacks effective drugs for prevention of fibrosis. Fluorofenidone is a
      newly developed drug with anti-fibrotic activity, which provides a new hope for
      treating the progressive fibrotic diseases. Recent studies have shown that
      fluorofenidone is a multifunctional small molecule with anti-inflammatory,
      antioxidative and anti-apoptotic eff ects. It can inhibit the activation and
      proliferation of myofibroblasts, promote the degradation of extracellular matrix
      and regulate the cellular signal transmission. Fluorofenidone can be applied to
      attenuate the progression of renal, hepatic and pulmonary fibrosis.

PMID- 25769330
TI  - [Effects of dexmedetomidine on recovery period of anesthesia and postoperative
      cognitive function after robot-assisted laparoscopicradical prostatectomy in the
      elderly people].
AB  - OBJECTIVE: To evaluate the neuroprotective effect of dexmedetomidine on recovery
      period of anesthesia and postoperative cognitive function after robot assisted
      laparoscopicradical prostatectomy in the elderly people. METHODS: A total of 100
      elderly patients who underwent robotic laparoscopic radical prostatectomy were
      divided into 2 groups: A dexmedetomidine group (n=50) and a control group (n=50).
      Patients in the dexmedetomidine group were given a loading dosage of
      dexmedetomidine [0.8 MUg/(kg.h)] intravenously 10 min before the induction of
      general anesthesia followed by continuous infusion [0.3 MUg/(kg.h)]. Patients in
      the control group were given 0.9% saline solution instead of dexmedetomidine.
      After pneumoperitoneum establishment, all patients adopted 40 degrees
      trendelenberg position. MAP, HR, and BIS from each patient at the end of surgery
      immediately (T0), wake up (T1), extubation (T2), 10 min after extubation (T3)
      were monitored. Ramsay score, surgery comfort score, postoperative delirium
      score, and VAS scores were measured. At the time of preoperative 1 d,
      postoperative 1 d or 5 d, cognitive function was assessed and the concentration
      of neuron-specific enolase (NSE), tumor necrosis factor-alpha (TNF-alpha),
      superoxide dismutase (SOD) and interleukin-6 (IL-6) were detected. RESULTS: In
      the dexmedetomidine group, delirium rating scale was significantly smaller than
      that of the control group (P<0.05) while Ramsay sedation score was significantly
      greater than that of the control group (P<0.05). The levels of TNF-alpha, NSE,
      and IL-6 in the dexmedetomidine group were significantly reduced compared with
      those in the control group (P<0.05). The level of SOD in the dexmedetomidine
      group significantly elevated compared with that in the control group (P<0.05).
      Seventeen patients in the control group and 11 in the dexmedetomidine group
      displayed postoperative cognitive dysfunction (POCD) at the 1st day after
      surgery. Meanwhile, 12 patients in the control group and 9 in the dexmedetomidine
      group showed POCD at the 5th day after surgery (P<0.05). CONCLUSION:
      Dexmedetomidine could exert a neuroprotective effect on elderly patients in
      robotic-assisted laparoscopic radical prostatectomy in recovery period of
      anesthesia and postoperative recovery period, which might be related to the
      reduction of inflammatory reaction by dexmedetomidine.

PMID- 25769331
TI  - [Regulation of retinal neovascularization in mice treated by recombinant PGC
      1alpha protein].
AB  - OBJECTIVE: To evaluate the regulatory effect of recombinant peroxisome
      proliferatoractivatedreceptor- gamma coactivator-1alpha (PGC-1alpha) on retinal
      neovascularization in mice. METHODS: Forty 7-day-old C57BL/6J mice were randomly
      divided into 2 groups including a normal injection group and a normal control
      group. Additional 40 7-day-old C57BL/6J mice were randomly divided into 2 groups
      including a model injection group and a model control group, in which the mice
      were induced retinal neovascularization by hypoxia. Liposome with recombinant PGC
      1alpha protein was injected into the vitreous of mice in the normal injection
      group and the model injection group at postnatal day 12 (P12). No injection was
      performed in the control group. Fluorescein angiography was used to assess the
      vascular pattern. The proliferative neovascular response was quantified by
      counting the nuclei of new vessels extending from the retina into the vitreous in
      cross-sections. PGC-1alpha levels in retina were measured by Western blot, and
      the vascular endothelial growth factor (VEGF) level in retina was measured by
      quantitative Real-time polymerase chain reaction and Western blot. RESULTS:
      Neovascular tuft was found in the normal injection group, but there was almost no
      neovascular tuft in the normal control group. Neovascular tuft and fluorescein
      leakage were increased in the model injection group compared with the model
      control group. The neovascular nuclei were increased both in the normal injection
      group and the model injection group compared with the control group (P<0.01). The
      expression of PGC-1alpha protein in retina was increased significantly both in
      the normal injection group and the model injection group as compared with the
      normal control group and the model control group, respectively (P<0.01). The
      expression of VEGF mRNA and protein in retina was increased significantly both in
      the normal injection group and the model injection group as compared with the
      normal control group and the model control group, respectively (P<0.01).
      CONCLUSION: PGC-1alpha can induce the formation of retinal neovascularization in
      the mice.

PMID- 25769332
TI  - [A long-term study regarding the therapeutic effect of two titanium screw
      fixation for femoral neck fractures].
AB  - OBJECTIVE: To observe the long-term efficacy of two double-head compression
      titanium screw anterior and posterior cross internal fixation on femoral neck
      fracture. METHODS: A total of 80 patients with the femoral neck fracture, from
      January 2010 to December 2013 in the Second Xiangya Hospital, Central South
      University, were selected and divided into an experimental group (n=50) and a
      control group (n=30). Th e experimental group received the treatment of two
      compression titanium screw anterior and posterior internal fixation, while the
      control group received three titanium screw internal fixation. Surgery time and
      intraoperative blood loss and postoperative Harris hip score were compared
      between the 2 groups. RESULTS: Th e operative time in the experimental group was
      (41.6+/-6.4) min, which was shorter than that in the control group [(50.1+/-7.2)
      min], the postoperative bleeding loss was (20.2+/-8.1) mL, which was less than
      that in the control group [(31.4+/-9.8) mL], with significant difference (both
      P<0.05). The excellence rate of Harris hip score was 94.0% in the experimental
      group, while that in the control group was 93.3%, with no significant difference
      (P>0.05). CONCLUSION: Two double-head compression titanium anterior and posterior
      cross internal fixation shows a good long-term efficacy on femoral neck fracture,
      which holds important clinical value and should be widely spread.

PMID- 25769333
TI  - [A SAS marco program for batch processing of univariate Cox regression analysis
      for great database].
AB  - OBJECTIVE: To realize batch processing of univariate Cox regression analysis for
      great database by SAS marco program. METHODS: We wrote a SAS macro program, which
      can filter, integrate, and export P values to Excel by SAS9.2. The program was
      used for screening survival correlated RNA molecules of ovarian cancer. RESULTS:
      A SAS marco program could finish the batch processing of univariate Cox
      regression analysis, the selection and export of the results. CONCLUSION: The SAS
      macro program has potential applications in reducing the workload of statistical
      analysis and providing a basis for batch processing of univariate Cox regression
      analysis.

PMID- 25769334
TI  - [Effect of reinforced health education on deep radiofrequency thermotherapy for
      patients with tumor].
AB  - OBJECTIVE: To explore the effect of reinforced health education on deep
      radiofrequency thermotherapy for patients with tumor. METHODS: From June 2012 to
      June 2014, 106 patients who underwent deep radiofrequency thermotherapy in our
      hospital were randomly selected, and were divided into a control group (n=69) and
      an observation group (n=65). The observation group received reinforced health
      education while the control group received the traditional health education
      before treatment. Th e reinforced health education included preparation,
      cooperation and health behavior during and aft er treatment. Th en the compliance
      rate, degree of satisfaction, and the awareness rate of related knowledge were
      compared and analyzed aft er treatment between the 2 groups. RESULTS: Th e
      compliance rate in the observation group and the control group was 85.51% and
      63.08% respectively; there was significant difference in the awareness rates of
      related knowledge and the overall degree of satisfaction between the patients and
      their family members (all P<0.05). CONCLUSION: Implement of reinforced health
      education is benefit to patients to understand the content of health education
      before treatment and keep health behavior after treatment, and can also improve
      the compliance, the degree of satisfaction in the deep radiofrequency
      thermotherapy for patients with tumor.

PMID- 25769335
TI  - [Study on medical service supply public-private partnership mode: based on the
      view of public economics].
AB  - Due to the quasi-public attributes of medical service, the supply mode and system
      could influence equity and fairness of general people's health. Based on the view
      of public economics, the purpose of this paper was to explain the economic nature
      of medical service supply. By analyzing the practice of public-private
      partnership (PPP) mode in medical care supply and the related public economic
      issues, we summarized the feasibility and risks of PPP model in Chinese medical
      care supply market. Finally, we discussed the innovative medical service system
      provided by government, public hospitals, and social capitals together.
      Therefore, to guarantee further development of this new medical service supply-
      PPP mode, we should pay attention to some practical problems, such as the share
      of cooperation cost and the balance between the benefit and risk among all
      partners.

PMID- 25769336
TI  - [Effect of implementation of essential medicine system in the primary health care
      institution in China].
AB  - Our primary health care institution began to implement national essential
      medicine system in 2009. In past fi ve years, the goal of national essential
      medicine system has been initially achieved. For examples, medicine price is
      steadily reducing, the quality of medical services is improving and residents'
      satisfaction is substantial increasing every year. However, at the same time, we
      also found some urgent problems needed to be solved. For examples, the range of
      national essential medicine is limited, which is difficult to guarantee the
      quality of essential medication. In addition, how to compensate the primary
      health care institution is still a question. 

PMID- 25769337
TI  - Biophysical modelling of intra-ring variations in tracheid features and wood
      density of Pinus pinaster trees exposed to seasonal droughts.
AB  - Process-based models that link seasonally varying environmental signals to
      morphological features within tree rings are essential tools to predict tree
      growth response and commercially important wood quality traits under future
      climate scenarios. This study evaluated model portrayal of radial growth and wood
      anatomy observations within a mature maritime pine (Pinus pinaster (L.) Ait.)
      stand exposed to seasonal droughts. Intra-annual variations in tracheid anatomy
      and wood density were identified through image analysis and X-ray densitometry on
      stem cores covering the growth period 1999-2010. A cambial growth model was
      integrated with modelled plant water status and sugar availability from the soil
      plant-atmosphere transfer model MuSICA to generate estimates of cell number, cell
      volume, cell mass and wood density on a weekly time step. The model successfully
      predicted inter-annual variations in cell number, ring width and maximum wood
      density. The model was also able to predict the occurrence of special anatomical
      features such as intra-annual density fluctuations (IADFs) in growth rings. Since
      cell wall thickness remained surprisingly constant within and between growth
      rings, variations in wood density were primarily the result of variations in
      lumen diameter, both in the model and anatomical data. In the model, changes in
      plant water status were identified as the main driver of the IADFs through a
      direct effect on cell volume. The anatomy data also revealed that a trade-off
      existed between hydraulic safety and hydraulic efficiency. Although a simplified
      description of cambial physiology is presented, this integrated modelling
      approach shows potential value for identifying universal patterns of tree-ring
      growth and anatomical features over a broad climatic gradient. 

PMID- 25769338
TI  - Stomatal sensitivity to vapour pressure deficit relates to climate of origin in
      Eucalyptus species.
AB  - Selecting plantation species to balance water use and production requires
      accurate models for predicting how species will tolerate and respond to
      environmental conditions. Although interspecific variation in water use occurs,
      species-specific parameters are rarely incorporated into physiologically based
      models because often the appropriate species parameters are lacking. To determine
      the physiological control over water use in Eucalyptus, five stands of Eucalyptus
      species growing in a common garden were measured for sap flux rates and their
      stomatal response to vapour pressure deficit (D) was assessed. Maximal canopy
      conductance and whole-canopy stomatal sensitivity to D and reduced water
      availability were lower in species originating from more arid climates of origin
      than those from humid climates. Species from humid climates showed a larger
      decline in maximal sap flux density (JSmax) with reduced water availability, and
      a lower D at which stomatal closure occurred than species from more arid
      climates, implying larger sensitivity to water availability and D in these
      species. We observed significant (P < 0.05) correlations of species climate of
      origin with mean vessel diameter (R(2) = 0.90), stomatal sensitivity to D (R(2) =
      0.83) and the size of the decline in JSmax to restricted water availability (R(2)
      = 0.94). Thus aridity of climate of origin appears to have a selective role in
      constraining water-use response among the five Eucalyptus plantation species.
      These relationships emphasize that within this congeneric group of species,
      climate aridity constrains water use. These relationships have implications for
      species choices for tree plantation success against drought-induced losses and
      the ability to manage Eucalyptus plantations against projected changes in water
      availability and evaporation in the future. 

PMID- 25769339
TI  - Allocation to carbon storage pools in Norway spruce saplings under drought and
      low CO2.
AB  - Non-structural carbohydrates (NSCs) are critical to maintain plant metabolism
      under stressful environmental conditions, but we do not fully understand how NSC
      allocation and utilization from storage varies with stress. While it has become
      established that storage allocation is unlikely to be a mere overflow process,
      very little empirical evidence has been produced to support this view, at least
      not for trees. Here we present the results of an intensively monitored
      experimental manipulation of whole-tree carbon (C) balance (young Picea abies
      (L.) H Karst.) using reduced atmospheric [CO2] and drought to reduce C sources.
      We measured specific C storage pools (glucose, fructose, sucrose, starch) over 21
      weeks and converted concentration measurement into fluxes into and out of the
      storage pool. Continuous labeling ((13)C) allowed us to track C allocation to
      biomass and non-structural C pools. Net C fluxes into the storage pool occurred
      mainly when the C balance was positive. Storage pools increased during periods of
      positive C gain and were reduced under negative C gain. (13)C data showed that C
      was allocated to storage pools independent of the net flux and even under severe
      C limitation. Allocation to below-ground tissues was strongest in control trees
      followed by trees experiencing drought followed by those grown under low [CO2].
      Our data suggest that NSC storage has, under the conditions of our experimental
      manipulation (e.g., strong progressive drought, no above-ground growth), a high
      allocation priority and cannot be considered an overflow process. While these
      results also suggest active storage allocation, definitive proof of active plant
      control of storage in woody plants requires studies involving molecular tools. 

PMID- 25769340
TI  - Ecophysiological response to seasonal variations in water availability in the
      arborescent, endemic plant Vellozia gigantea.
AB  - The physiological response of plants growing in their natural habitat is strongly
      determined by seasonal variations in environmental conditions and the interaction
      of abiotic and biotic stresses. Here, leaf water and nutrient contents, changes
      in cellular redox state and endogenous levels of stress-related phytohormones
      (abscisic acid (ABA), salicylic acid and jasmonates) were examined during the
      rainy and dry season in Vellozia gigantea, an endemic species growing at high
      elevations in the rupestrian fields of the Espinhaco Range in Brazil. Enhanced
      stomatal closure and increased ABA levels during the dry season were associated
      with an efficient control of leaf water content. Moreover, reductions in 12-oxo
      phytodienoic acid (OPDA) levels during the dry season were observed, while levels
      of other jasmonates, such as jasmonic acid and jasmonoyl-isoleucine, were not
      affected. Changes in ABA and OPDA levels correlated with endogenous
      concentrations of iron and silicon, hydrogen peroxide, and vitamin E, thus
      indicating complex interactions between water and nutrient contents, changes in
      cellular redox state and endogenous hormone concentrations. Results also
      suggested crosstalk between activation of mechanisms for drought stress tolerance
      (as mediated by ABA) and biotic stress resistance (mediated by jasmonates), in
      which vitamin E levels may serve as a control point. It is concluded that, aside
      from a tight ABA-associated regulation of stomatal closure during the dry season,
      crosstalk between activation of abiotic and biotic defences, and nutrient
      accumulation in leaves may be important modulators of plant stress responses in
      plants growing in their natural habitat. 

PMID- 25769341
TI  - Photon-impenetrable, electron-permeable: the carbon nanotube forest as a medium
      for multiphoton thermal-photoemission.
AB  - Combining the photoelectric and thermionic mechanisms to generate free electrons
      has been of great interest since the early days of quantum physics as exemplified
      by the Fowler-DuBridge theory, and recently proposed for highly efficient solar
      conversion. We present experimental evidence of this combined effect over the
      entire range spanning room-temperature photoemission to thermionic emission.
      Remarkably, the optical stimulus alone is responsible for both heating and
      photoemission at the same time. Moreover, the current depends on optical
      intensity quadratically, indicating two-photon photoemission, for intensities of
      ca. 1-50 W/cm(2), which are orders of magnitude below the intensities required
      for two-photon photoemission from bulk metals. This surprising behavior appears
      to be enabled by the internal nanostructure of the carbon nanotube forest, which
      captures photons effectively, yet allows electrons to escape easily. 

PMID- 25769342
TI  - Air-stable transport in graphene-contacted, fully encapsulated ultrathin black
      phosphorus-based field-effect transistors.
AB  - The presence of direct bandgap and high mobility in semiconductor few-layer black
      phosphorus offers an attractive prospect for using this material in future two
      dimensional electronic devices. However, creation of barrier-free contacts which
      is necessary to achieve high performance in black phosphorus-based devices is
      challenging and currently limits their potential for applications. Here, we
      characterize fully encapsulated ultrathin (down to bilayer) black phosphorus
      field effect transistors fabricated under inert gas conditions by utilizing
      graphene as source-drain electrodes and boron nitride as an encapsulation layer.
      The observation of a linear ISD-VSD behavior with negligible temperature
      dependence shows that graphene electrodes lead to barrier-free contacts, solving
      the issue of Schottky barrier limited transport in the technologically relevant
      two-terminal field-effect transistor geometry. Such one-atom-thick conformal
      source-drain electrodes also enable the black phosphorus surface to be sealed, to
      avoid rapid degradation, with the inert boron nitride encapsulating layer. This
      architecture, generally applicable for other sensitive two-dimensional crystals,
      results in air-stable, hysteresis-free transport characteristics. 

PMID- 25769343
TI  - Completely transparent conducting oxide-free and flexible dye-sensitized solar
      cells fabricated on plastic substrates.
AB  - To achieve commercialization and widespread application of next-generation
      photovoltaics, it is important to develop flexible and cost-effective devices.
      Given this, the elimination of expensive transparent conducting oxides (TCO) and
      replacement of conventional glass substrates with flexible plastic substrates
      presents a viable strategy to realize extremely low-cost photovoltaics with a
      potentially wide applicability. To this end, we report a completely TCO-free and
      flexible dye-sensitized solar cell (DSSC) fabricated on a plastic substrate using
      a unique transfer method and back-contact architecture. By adopting unique
      transfer techniques, the working and counter electrodes were fabricated by
      transferring high-temperature-annealed TiO2 and Pt/carbon films, respectively,
      onto flexible plastic substrates without any exfoliation. The fabricated working
      electrode with the conventional counter electrode exhibited a record efficiency
      for flexible DSSCs of 8.10%, despite its TCO-free structure. In addition, the
      completely TCO-free and flexible DSSC exhibited a remarkable efficiency of 7.27%.
      Furthermore, by using an organic hole-transporting material (spiro-MeOTAD) with
      the same transfer method, solid-state flexible TCO-free DSSCs were also
      successfully fabricated, yielding a promising efficiency of 3.36%. 

PMID- 25769344
TI  - "BINACLE" assay for in vitro detection of active tetanus neurotoxin in toxoids.
AB  - Tetanus neurotoxin (TeNT) consists of two protein chains connected by a disulfide
      linkage: The heavy chain mediates the toxin binding and uptake by neurons,
      whereas the light chain cleaves synaptobrevin and thus blocks neurotransmitter
      release.Chemically inactivated TeNT (tetanus toxoid) is utilized for the
      production of tetanus vaccines. For safety reasons, each toxoid bulk has to be
      tested for the "absence of toxin and irreversibility of toxoid". To date, these
      mandatory tests are performed as toxicity tests in guinea pigs. A replacement by
      an animal-free method for the detection of TeNT would be desirable. The BINACLE
      (BINding And CLEavage) assay takes into account the receptor-binding as well as
      the proteolytic characteristics of TeNT: The toxin is bound to immobilized
      receptor molecules, the light chains are then released by reduction and
      transferred to a microplate containing synaptobrevin, and the fragment resulting
      from TeNT-induced cleavage is finally detected. This assay offers a higher
      specificity for discriminating between toxic TeNT and inactivated toxoid
      molecules than other published assays. Validation studies have shown that the
      BINACLE assay allows the sensitive and robust detection of TeNT in toxoids, and
      thus may indeed represent a suitable alternative to the prescribed animal safety
      tests for toxoids from several European vaccine manufacturers. Product-specific
      validations (and possibly adaptations) of the assay protocol will be required. A
      European collaborative study is currently being initiated to further examine the
      applicability of the method for toxoid testing. The final aim is the inclusion of
      the method into the European Pharmacopoeia.

PMID- 25769346
TI  - Are religiosity and prayer use related with multiple behavioural risk factors for
      chronic diseases in European adults aged 50+ years?
AB  - OBJECTIVES: Behavioural risk factors for chronic diseases involve factors
      relating to lifestyle habits. This study examined the relationship of religious
      and spiritual beliefs with the adoption and presence of multiple behavioural risk
      factors (MBRFs) in European adults. STUDY DESIGN: Cross-sectional study. METHODS:
      Data were used from 16,557 individuals, aged 50+ years, participating in the
      Survey of Health, Ageing and Retirement in Europe (2004/05). MBRFs clustering was
      defined by high body weight, smoking, physical inactivity and risky alcohol
      consumption, and regression estimations with religiosity and prayer use were
      assessed based on sampling weights. RESULTS: In total, 79.4% of participants had
      received religious education, 33.4% had used prayer '>=1 time/day' and 53.3% had
      clustering of 2+ MBRFs. Lower prevalence of smoking was found in males (20.6% vs.
      29.4%, P < 0.05), as well as in females (13.1% vs. 22.6%, P < 0.05), who prayed
      '>=1 time/day', compared to those who never prayed. Categorical regression
      analysis revealed that the presence of MBRFs was associated negatively with
      religious education (standardized beta = -0.048, P < 0.001) and positively with
      low frequency of prayer use (standardized beta = 0.056, P < 0.001). CONCLUSIONS:
      Having received religious education and prayer use were related to the presence
      of fewer MBRFs in European adults aged 50+ years. These lifestyle factors should
      be assessed as potential determinants of MBRFs adoption when examining chronic
      disease development in multicultural populations.

PMID- 25769345
TI  - Functional genomic analysis reveals overlapping and distinct features of
      chronologically long-lived yeast populations.
AB  - Yeast chronological lifespan (CLS) is extended by multiple genetic and
      environmental manipulations, including caloric restriction (CR). Understanding
      the common changes in molecular pathways induced by such manipulations could
      potentially reveal conserved longevity mechanisms. We therefore performed gene
      expression profiling on several long-lived yeast populations, including
      anade4?mutant defective in de novo purine (AMP) biosynthesis, and a calorie
      restricted WT strain. CLS was also extended by isonicotinamide (INAM) or expired
      media derived from CR cultures. Comparisons between these diverse long-lived
      conditions revealed a common set of differentially regulated genes, several of
      which were potential longevity biomarkers. There was also enrichment for genes
      that function in CLS regulation, including a long-lived adenosine kinase mutant
      (ado1?) that links CLS regulation to the methyl cycle and AMP. Genes co-regulated
      between the CR and ade4? conditions were dominated by GO terms related to
      metabolism of alternative carbon sources, consistent with chronological longevity
      requiring efficient acetate/acetic acid utilization. Alternatively, treating
      cells with isonicotinamide (INAM) or the expired CR media resulted in GO terms
      predominantly related to cell wall remodeling, consistent with improved stress
      resistance and protection against external insults like acetic acid. Acetic acid
      therefore has both beneficial and detrimental effects on CLS. 

PMID- 25769347
TI  - Developing a conceptual framework and a tool for measuring access to, and use of,
      medicines at household level (HH-ATM tool).
AB  - OBJECTIVE: To develop a valid and reliable tool to evaluate access to, and use
      of, medicines at household level (HH-ATM tool). STUDY DESIGN: The Behavioral
      Model of Health Services Use was adapted and used as the conceptual framework for
      developing the HH-ATM tool. Questionnaires were designed (individual and
      household) based on the conceptual framework and existing tools, including items
      that captured the characteristics of predisposing, enabling and need factors;
      health care behaviours; outcomes and impacts. METHODS: Face validity, content
      validity and test-retest reliability were assessed using inter-rater agreement,
      item and scale content validity indices, comprehensiveness indices, and intra
      class correlation, kappa and weighted-kappa coefficients. RESULTS: The household
      and individual questionnaires demonstrated appropriate validity and reliability.
      The content validity of household questionnaire was favourable, with inter-rater
      agreement of 86% and 91% for relevance and clarity, respectively. Scale content
      validity indices for relevance and clarity were 89% and 91%, respectively, and
      comprehensiveness was scored at 100%. These indices were also favourable for the
      individual questionnaire, all scoring 94% or higher. CONCLUSION: The
      questionnaires showed excellent validity and reliability for use in Iran. The HH
      ATM tool can be implemented to evaluate access to, and use of, medicines in Farsi
      speaking communities, and may be useful in other communities if adapted
      appropriately.

PMID- 25769348
TI  - Poor health among smokers obtaining colonoscopy screening: making the case for
      cessation intervention.
AB  - OBJECTIVES: Assess differences in perceived health status among individuals
      receiving colonoscopy screening based on smoking status. STUDY DESIGN: Cross
      sectional data were collected as part of a larger study investigating whether
      verbal and non-verbal communication and behaviors of gastroenterologists and
      nurses. METHOD: Data for this study were collected between 2011 and 2013 among
      receiving colonoscopy screenings. Data were collected as part of a study
      assessing patients (n = 1785) undergoing colonoscopy screenings about their
      expectations, concerns, understanding of the procedure, and perceived health
      status. Differences between current, former and never smokers were analyzed using
      a one-way between subjects ANOVA, with a Scheffe post hoc. RESULTS: Post hoc
      analyses revealed that current smokers were significantly different from former
      or never smokers on the following variables: days their physical health was not
      good, days their mental health was not good, days health influenced their
      activities, days pain influenced their ability to perform activities, perceived
      general health, and current anxiety. CONCLUSION: This study looked at perceived
      health among individuals receiving colonoscopy screening by on smoking status, a
      relevant population based on the recent Surgeon Generals link. Former smokers
      reported similar health status across all variables as never smokers, suggesting
      the effect of quitting smoking on self-perceived health. With this link, tailored
      smoking cessation messages to smokers receiving colonoscopy screenings may be an
      excellent vantage point for a smoking cessation intervention.

PMID- 25769349
TI  - Potential years of life lost due to suicide in China, 2006-2010.
AB  - OBJECTIVES: To calculate the potential years of life lost (PYLL) due to suicide
      in China, and analyse the distribution of PYLL by age, sex and region. STUDY
      DESIGN: The recent Chinese national mortality data (2006-2010) published by the
      Chinese Ministry of Health and the census data provided by the Chinese National
      Population Census were used to calculate PYLL due to suicide. METHODS: Age-, sex-
      and region-specific PYLL due to suicide in China were determined for victims aged
      between 1 and 74 years. RESULTS: Suicide was found to be the 10th leading cause
      of death in terms of PYLL, and accounted for 3.06% of all PYLL in China. There
      were three age peaks for PYLL due to suicide in rural areas (20-24, 35-44 and 50
      59 years), and two peaks for PYLL due to suicide in urban areas (20-24 and 35-44
      years). PYLL due to suicide in rural areas was approximately two-fold higher than
      PYLL due to suicide in urban areas. CONCLUSIONS: Suicide is a major public health
      problem in China. This needs to be controlled, especially in rural areas.

PMID- 25769350
TI  - Long-term supplementation with a low dose of proanthocyanidins normalized liver
      miR-33a and miR-122 levels in high-fat diet-induced obese rats.
AB  - Deregulation of miR-33 and miR-122, as major regulators of lipid metabolism in
      liver, has been related to obesity and metabolic syndrome. Proanthocyanidins
      repress these microRNAs in healthy animals. Hence, we hypothesized that long-term
      consumption of dietary proanthocyanidins can normalize the expression of miR-33a
      and miR-122. Therefore, the objective of this work was to determine whether the
      long-term consumption of proanthocyanidins could effectively normalize the
      expression of miR-33a and miR-122 in rats made obese by a high-fat diet and to
      determine the effective dose. Rats were maintained on the high-fat diet with or
      without supplementation with a grape seed proanthocyanidin extract at low,
      medium, or high dose in relation to human consumption. Results show that 3 weeks
      of supplementation with grape seed proanthocyanidin extract normalized the
      overexpression of miR-33a and miR-122 in obese rats' liver for all doses studied,
      with no dose-dependent outcome, and also reduced the levels of plasma and liver
      lipids in a dose-dependent manner. In conclusion, a low sustained dose of
      proanthocyanidins, lower than the estimated mean intake for a European
      population, is enough to normalize miR-33a and miR-122 levels in the livers of
      obese rats. Therefore, a proanthocyanidin-rich diet during obesity can improve
      some of the metabolic syndrome symptoms at least at the molecular level. 

PMID- 25769351
TI  - Imaging innovations in temporal bone disorders.
AB  - The development of new imaging techniques coupled with new treatment algorithms
      has created new possibilities in treating temporal bone diseases. This article
      provides an overview of recent imaging innovations that can be applied to
      temporal bone diseases. Topics covered include the role of magnetic resonance
      (MR) diffusion-weighted imaging in cholesteatomas and skull base epidermoids,
      whole-body molecular imaging in paragangliomas of the jugular foramen, and MR
      arterial spin labeling perfusion for dural arteriovenous fistulas and
      arteriovenous malformations. 

PMID- 25769352
TI  - Squamous cell carcinoma of the temporal bone.
AB  - Temporal bone malignancy presents a significant clinical challenge for the
      otolaryngologist. This article provides an overview of squamous cell carcinoma of
      the temporal bone, including clinical presentation, diagnosis, staging,
      treatment, and prognosis. As demonstrated in this case study, the prognosis for
      patients with advanced-stage temporal bone malignancy is poor, even with maximal
      therapy. 

PMID- 25769353
TI  - Adenomatous tumors of the middle ear.
AB  - Adenomatous tumors are an uncommon cause of a middle ear mass. Clinical findings
      may be nonspecific, leading to difficulties in differentiation from other middle
      ear tumors. Controversy also exists whether to classify middle ear adenoma and
      carcinoid as separate neoplasms, or alternatively within a spectrum of the same
      pathologic entity. Most adenomatous middle ear tumors are indolent in behavior,
      with a benign histologic appearance and slowly progressive growth. The mainstay
      of treatment is complete surgical resection, which affords the greatest
      likelihood of cure. 

PMID- 25769354
TI  - Contemporary management of jugular paragangliomas.
AB  - Jugular paragangliomas are generally benign slow-growing tumors that can cause
      pulsatile tinnitus, hearing loss, and cranial nerves neuropathy. Progressive
      growth can also lead to intracranial extension. Historically, the treatment of
      choice for these lesions has been gross total resection. However, over the last
      15 years, many groups have adopted less invasive management strategies including
      stereotactic radiation therapy, subtotal resection, and primary observation in
      order to reduce treatment-associated morbidity. The focus of this article is to
      review the modern management of jugular paraganglioma, highlighting the evolving
      treatment paradigm at the Otology Group of Vanderbilt.

PMID- 25769355
TI  - Tumors of the ear and lateral skull base: part I.

PMID- 25769356
TI  - Controlled supramolecular self-assembly of large nanoparticles in amphiphilic
      brush block copolymers.
AB  - To date the self-assembly of ordered metal nanoparticle (NP)/block copolymer
      hybrid materials has been limited to NPs with core diameters (D(core)) of less
      than 10 nm, which represents only a very small fraction of NPs with attractive
      size-dependent physical properties. Here this limitation has been circumvented
      using amphiphilic brush block copolymers as templates for the self-assembly of
      ordered, periodic hybrid materials containing large NPs beyond 10 nm. Gold NPs
      (D(core) = 15.8 +/- 1.3 nm) bearing poly(4-vinylphenol) ligands were selectively
      incorporated within the hydrophilic domains of a phase-separated (polynorbornene
      g-polystyrene)-b-(polynorbornene-g-poly(ethylene oxide)) copolymer via hydrogen
      bonding between the phenol groups on gold and the PEO side chains of the brush
      block copolymer. Well-ordered NP arrays with an inverse cylindrical morphology
      were readily generated through an NP-driven order-order transition of the brush
      block copolymer.

PMID- 25769357
TI  - Genetics and the clinical response to warfarin and edoxaban: findings from the
      randomised, double-blind ENGAGE AF-TIMI 48 trial.
AB  - BACKGROUND: Warfarin is the most widely used oral anticoagulant worldwide, but
      serious bleeding complications are common. We tested whether genetic variants can
      identify patients who are at increased risk of bleeding with warfarin and,
      consequently, those who would derive a greater safety benefit with a direct oral
      anticoagulant rather than warfarin. METHODS: ENGAGE AF-TIMI 48 was a randomised,
      double-blind trial in which patients with atrial fibrillation were assigned to
      warfarin to achieve a target international normalised ratio of 2.0-3.0, or to
      higher-dose (60 mg) or lower-dose (30 mg) edoxaban once daily. A subgroup of
      patients was included in a prespecified genetic analysis and genotyped for
      variants in CYP2C9 and VKORC1. The results were used to create three genotype
      functional bins (normal, sensitive, and highly sensitive responders to warfarin).
      This trial is registered with ClinicalTrials.gov, number NCT00781391. FINDINGS:
      14,348 patients were included in the genetic analysis. Of 4833 taking warfarin,
      2982 (61.7%) were classified as normal responders, 1711 (35.4%) as sensitive
      responders, and 140 (2.9%) as highly sensitive responders. Compared with normal
      responders, sensitive and highly sensitive responders spent greater proportions
      of time over-anticoagulated in the first 90 days of treatment (median 2.2%, IQR 0
      20.2; 8.4%, 0-25.8; and 18.3%, 0-32.6; ptrend<0.0001) and had increased risks of
      bleeding with warfarin (sensitive responders hazard ratio 1.31, 95% CI 1.05-1.64,
      p=0.0179; highly sensitive responders 2.66, 1.69-4.19, p<0.0001). Genotype added
      independent information beyond clinical risk scoring. During the first 90 days,
      when compared with warfarin, treatment with edoxaban reduced bleeding more so in
      sensitive and highly sensitive responders than in normal responders (higher-dose
      edoxaban pinteraction=0.0066; lower-dose edoxaban pinteraction=0.0036). After 90
      days, the reduction in bleeding risk with edoxaban versus warfarin was similarly
      beneficial across genotypes. INTERPRETATION: CYP2C9 and VKORC1 genotypes identify
      patients who are more likely to experience early bleeding with warfarin and who
      derive a greater early safety benefit from edoxaban compared with warfarin.
      FUNDING: Daiichi Sankyo.

PMID- 25769358
TI  - Antiretroviral chemoprophylaxis: new successes and questions.

PMID- 25769359
TI  - Edoxaban and the need for outcomes-based NOAC dosing.

PMID- 25769360
TI  - Pharmacogenomic testing and response to warfarin.

PMID- 25769361
TI  - Association between edoxaban dose, concentration, anti-Factor Xa activity, and
      outcomes: an analysis of data from the randomised, double-blind ENGAGE AF-TIMI 48
      trial.
AB  - BACKGROUND: New oral anticoagulants for stroke prevention in atrial fibrillation
      were developed to be given in fixed doses without the need for the routine
      monitoring that has hindered usage and acceptance of vitamin K antagonists. A
      concern has emerged, however, that measurement of drug concentration or
      anticoagulant activity might be needed to prevent excess drug concentrations,
      which significantly increase bleeding risk. In the ENGAGE AF-TIMI 48 trial,
      higher-dose and lower-dose edoxaban were compared with warfarin in patients with
      atrial fibrillation. Each regimen incorporated a 50% dose reduction in patients
      with clinical features known to increase edoxaban drug exposure. We aim to assess
      whether adjustment of edoxaban dose in this trial prevented excess drug
      concentration and the risk of bleeding events. METHODS: We analysed data from the
      randomised, double-blind ENGAGE AF-TIMI 48 trial. We correlated edoxaban dose,
      plasma concentration, and anti-Factor Xa (FXa) activity and compared efficacy and
      safety outcomes with warfarin stratified by dose reduction status. Patients with
      atrial fibrillation and at moderate to high risk of stroke were randomly assigned
      in a 1:1:1 ratio to receive warfarin, dose adjusted to an international
      normalised ratio of 2.0-3.0, higher-dose edoxaban (60 mg once daily), or lower
      dose edoxaban (30 mg once daily). Randomisation was done with use of a central,
      24 h, interactive, computerised response system. International normalised ratio
      was measured using an encrypted point-of-care device. To maintain masking, sham
      international normalised ratio values were generated for patients assigned to
      edoxaban. Edoxaban (or placebo-edoxaban in warfarin group) doses were halved at
      randomisation or during the trial if patients had creatinine clearance 30-50
      mL/min, bodyweight 60 kg or less, or concomitant medication with potent P
      glycoprotein interaction. Efficacy outcomes included the primary endpoint of all
      cause stroke or systemic embolism, ischaemic stroke, and all-cause mortality.
      Safety outcomes included the primary safety endpoint of major bleeding, fatal
      bleeding, intracranial haemorrhage, and gastrointestinal bleeding. This trial is
      registered with ClinicalTrials.gov, number NCT00781391. FINDINGS: Between Nov 19,
      2008 and Nov 22, 2010, 21 105 patients were recruited. Patients who met clinical
      criteria for dose reduction at randomisation (n=5356) had higher rates of stroke,
      bleeding, and death compared with those who did not have a dose reduction (n=15
      749). Edoxaban dose ranged from 15 mg to 60 mg, resulting in a two-fold to three
      fold gradient of mean trough drug exposure (16.0-48.5 ng/mL in 6780 patients with
      data available) and mean trough anti-FXa activity (0.35-0.85 IU/mL in 2865
      patients). Dose reduction decreased mean exposure by 29% (from 48.5 ng/mL [SD
      45.8] to 34.6 ng/mL [30.9]) and 35% (from 24.5 ng/mL [22.7] to 16.0 ng/mL [14.5])
      and mean anti-FXa activity by 25% (from 0.85 IU/mL [0.76] to 0.64 IU/mL [0.54])
      and 20% (from 0.44 IU/mL [0.37] to 0.35 IU/mL [0.28]) in the higher-dose and
      lower-dose regimens, respectively. Despite the lower anti-FXa activity, dose
      reduction preserved the efficacy of edoxaban compared with warfarin (stroke or
      systemic embolic event: higher dose pinteraction=0.85, lower dose
      pinteraction=0.99) and provided even greater safety (major bleeding: higher dose
      pinteraction 0.02, lower dose pinteraction=0.002). INTERPRETATION: These findings
      validate the strategy that tailoring of the dose of edoxaban on the basis of
      clinical factors alone achieves the dual goal of preventing excess drug
      concentrations and helps to optimise an individual patient's risk of ischaemic
      and bleeding events and show that the therapeutic window for edoxaban is narrower
      for major bleeding than thromboembolism. FUNDING: Daiichi-Sankyo Pharma
      Development.

PMID- 25769362
TI  - The Fukushima Daiichi disaster: 4 years on.

PMID- 25769363
TI  - Low-Level Laser Therapy at 635 nm for Treatment of Chronic Plantar Fasciitis: A
      Placebo-Controlled, Randomized Study.
AB  - Plantar fasciitis affects nearly 1 million persons in the United States at any
      one time. Conservative therapies have been reported to successfully treat 90% of
      plantar fasciitis cases; however, for the remaining cases, only invasive
      therapeutic solutions remain. This investigation studied newly emerging
      technology, low-level laser therapy. From September 2011 to June 2013, 69
      subjects were enrolled in a placebo-controlled, randomized, double-blind,
      multicenter study that evaluated the clinical utility of low-level laser therapy
      for the treatment of unilateral chronic fasciitis. The volunteer participants
      were treated twice a week for 3 weeks for a total of 6 treatments and were
      evaluated at 5 separate time points: before the procedure and at weeks 1, 2, 3,
      6, and 8. The pain rating was recorded using a visual analog scale, with 0
      representing "no pain" and 100 representing "worst pain." Additionally, Doppler
      ultrasonography was performed on the plantar fascia to measure the fascial
      thickness before and after treatment. Study participants also completed the Foot
      Function Index. At the final follow-up visit, the group participants demonstrated
      a mean improvement in heel pain with a visual analog scale score of 29.6 +/- 24.9
      compared with the placebo subjects, who reported a mean improvement of 5.4 +/-
      16.0, a statistically significant difference (p < .001). Although additional
      studies are warranted, these data have demonstrated that low-level laser therapy
      is a promising treatment of plantar fasciitis. 

PMID- 25769364
TI  - [Cystinosis in adults: A systemic disease].
AB  - Cystinosis is a multisystemic autosomal recessive disorder characterized by an
      intra-lysosomal accumulation of cystine. It is due to a defect of cystine
      transport through the membrane of the lysosome. The classical infantile form is
      characterized by a proximal tubulopathy, corneal cystine crystals and progressive
      renal failure, leading to end stage renal disease before 20 years of age in 90%
      of cases in historical cohorts. It is the most common cause of Fanconi syndrome
      in children. Due to recent progress in renal transplantation and to the specific
      treatment with cysteamine, patients survival improved significantly in the last
      years and adult nephrologists take care of such patients. However, disease
      evolution is characterized by other complications: endocrinological
      (hypothyroidism, diabetes, male hypogonadism), neuromuscular and of the central
      nervous system. Cysteamine delays the onset of these complications. A
      multidisciplinary team should take care of these patients, even if the
      nephrologist remains in first line. Apart from infantile form, there is a
      juvenile form, with a later onset, and an adult form, which may be only ocular,
      although renal involvement may be associated. The aim of this revue is to
      summarize actual knowledge of the disease to provide guidance to adult
      nephrologist to take care of his patients. 

PMID- 25769365
TI  - [Dealing with competing events in survival analysis].
AB  - Survival analyses focus on the occurrences of an event of interest, in order to
      determine risk factors and estimate a risk. Competing events prevent from
      observing the event of interest. If there are competing events, it can lead to a
      bias in the risk's estimation. The aim of this article is to explain why Cox
      model is not appropriate when there are competing events, and to present Fine and
      Gray model, which can help when dealing with competing risks. 

PMID- 25769366
TI  - Prevention and control of healthcare-associated infection in Europe: a review of
      patients' perspectives and existing differences.
AB  - European healthcare systems are under increasing pressure owing to demographic
      change, the upsurge of chronic diseases, and declining budgets. Yet the
      increasing threat posed by antimicrobial resistance calls for better
      surveillance, prevention and control of infection. Moreover, the increasing
      emphasis on cross-border mobility calls for better integration of these
      activities across Europe. This paper reviews European initiatives to achieve
      these goals and to increase patient involvement in healthcare safety at political
      and institutional levels. 

PMID- 25769367
TI  - PET/MRI and PET/MRI/SISCOM coregistration in the presurgical evaluation of
      refractory focal epilepsy.
AB  - We aimed to investigate the usefulness of coregistration of positron emission
      tomography (PET) and magnetic resonance imaging (MRI) findings (PET/MRI) and of
      coregistration of PET/MRI with subtraction ictal single-photon emission computed
      tomography (SPECT) coregistered to MRI (SISCOM) (PET/MRI/SISCOM) in localizing
      the potential epileptogenic zone in patients with drug-resistant epilepsy. We
      prospectively included 35 consecutive patients with refractory focal epilepsy
      whose presurgical evaluation included a PET study. Separately acquired PET and
      structural MRI images were coregistered for each patient. When possible, ictal
      SPECT and SISCOM were obtained and coregistered with PET/MRI. The potential
      location of the epileptogenic zone determined by neuroimaging was compared with
      the seizure onset zone determined by long-term video-EEG monitoring and with
      invasive EEG studies in patients who were implanted. Structural MRI showed no
      lesions in 15 patients. In these patients, PET/MRI coregistration showed a
      hypometabolic area in 12 (80%) patients that was concordant with seizure onset
      zone on EEG in 9. In 7 patients without MRI lesions, PET/MRI detected a
      hypometabolism that was undetected on PET alone. SISCOM, obtained in 25 patients,
      showed an area of hyperperfusion concordant with the seizure onset zone on EEG in
      7 (58%) of the 12 of these patients who had normal MRI findings. SISCOM
      hyperperfusion was less extensive than PET hypometabolism. A total of 19 patients
      underwent surgery; 11 of these underwent invasive-EEG monitoring and the seizure
      onset zone was concordant with PET/MRI in all cases. PET/MRI/SISCOM
      coregistration, performed in 4 of these patients, was concordant in 3 (75%).
      After epilepsy surgery, 13 (68%) patients are seizure-free after a mean follow-up
      of 4.5 years. PET/MRI and PET/MRI/SISCOM coregistration are useful for
      determining the potential epileptogenic zone and thus for planning invasive EEG
      studies and surgery more precisely, especially in patients without lesions on
      MRI. 

PMID- 25769368
TI  - Consanguinity and epilepsy in Oran, Algeria: A case-control study.
AB  - PURPOSE: The goal of this case-control study was to identify the significance of
      consanguinity and other risk factors for epilepsy in Oran, Algeria. METHODS:
      Unrelated epileptic patients upwards of 16 years, who attended the Neurology
      Department between October 2013 and March 2014 were included in the study.
      Controls, matched for age and sex, were selected among non-epileptic patients
      attending the same department during the same period. The risk factors evaluated
      were: consanguinity, family history of epilepsy, perinatal complications,
      infection of the central nervous system, mental retardation, neurological
      impairment, history of febrile seizures, severe head trauma, cerebrovascular
      diseases, and addiction. RESULTS: 101 cases and 202 controls participated in the
      study. Multivariate logistic regression identified five factors significantly
      associated with epilepsy: first-degree of consanguinity (odds ratio (OR)=2.15),
      history of epilepsy in first-degree relatives (OR=4.03), antecedent of febrile
      seizures (OR=5.38), severe head injury (OR=2.94) and mental retardation
      (OR=9.32). CONCLUSION: Consanguinity, family history of epilepsy, history of
      febrile seizures, severe head trauma and mental retardation are risk factors for
      epilepsy. The implementation of a strategy for prevention and awareness of the
      impact of consanguineous marriages as well as genetic counseling for couples with
      a family history of epilepsy are needed.

PMID- 25769369
TI  - Hippocampal serotonin depletion is related to the presence of generalized tonic
      clonic seizures, but not to psychiatric disorders in patients with temporal lobe
      epilepsy.
AB  - OBJECTIVE: Previous studies suggest that concentration of serotonin ([5-HT])
      plays a pathogenic role in various types of epilepsy inhibiting seizures.
      However, most have not considered the clinical variables of epilepsy, and all of
      these studies included small and heterogeneous samples with refractory epilepsy,
      regardless of etiology. In this work, we measured [5-HT]s in hippocampal tissues
      from a large series of patients with refractory temporal lobe epilepsy caused by
      hippocampal sclerosis who underwent epilepsy surgery and evaluated the
      relationship between [5HT] and epilepsy-related clinical variables and
      psychiatric disorders. METHODS: We included 44 patients with refractory
      unilateral TLE-HS who underwent surgical treatment for epilepsy. Hippocampal
      samples were collected, and serotonin concentrations were measured with high
      pressure liquid chromatography (HPLC). RESULTS: Lower [5-HT]s were correlated
      with a history of GTC seizures (Student's t-test: p 0.041). There were no
      differences in [5-HT]s according to the other clinical variables and the presence
      of psychiatric disorders. SIGNIFICANCE: Our findings demonstrated that serotonin
      depletion in the hippocampus play an important role in some aspects of the
      severity of epilepsy (i.e., the presence of GTC seizures) in a homogeneous sample
      of patients with refractory temporal lobe epilepsy determined by hippocampal
      sclerosis, but not with the presence of psychiatric disorders.

PMID- 25769370
TI  - Selective amygdalohippocampectomy versus standard temporal lobectomy in patients
      with mesiotemporal lobe epilepsy and unilateral hippocampal sclerosis: post
      operative facial emotion recognition abilities.
AB  - Surgical treatment of mesial temporal lobe epilepsy (mTLE) patients involves the
      removal either of the left or the right hippocampus. Since the mesial temporal
      lobe is responsible for emotion recognition abilities, we aimed to assess facial
      emotion recognition (FER) in two homogeneous patient cohorts that differed only
      in the administered surgery design since anterior temporal lobectomy (ATL) or
      selective amygdalohippocampectomy (SAH) were performed independently of the
      underlying electroclinical conditions. The patient selection for the two
      respective surgical procedures was carried out retrospectively between 2000 and
      2009 by two independent epilepsy centres, the Kork Epilepsy Centre, Germany and
      the University Hospital of Strasbourg, France. All included patients had
      presented with unilateral hippocampus sclerosis (HS) without associated dysplasia
      or white matter blurring and had become seizure-free postoperatively.
      Psychometric evaluation was carried out with the Ekman 60 Faces Test and screened
      for depression and psychosomatic symptoms with the SCL-90 R and the BDI. Thirty
      healthy volunteers participated as control subjects. Sixty patients were
      included, 27 had undergone SAH and 33 ATL. Patients and controls obtained
      comparable scores in FER for surprise, happiness, anger and sadness. Concerning
      fear and disgust the patient group scored significantly worse. Left-sided
      operations led to the the most pronounced impairment. The ATL group scored
      significantly worse for recognition of fear compared with SAH patients.
      Inversely, after SAH scores for disgust were significantly lower than after ATL,
      independently of the side of resection. Unilateral temporal damage impairs FER.
      Different neurosurgical procedures may affect FER differently. 

PMID- 25769371
TI  - Attenuation of kainic acid-induced status epilepticus by inhibition of
      endocannabinoid transport and degradation in guinea pigs.
AB  - Status epilepticus (SE) is a medical emergency associated with a high rate of
      mortality if not treated promptly. Exogenous and endogenous cannabinoids have
      been shown to possess anticonvulsant properties both in vivo and in vitro. Here
      we study the influence of endocannabinoid metabolism on the development of kainic
      acid-induced SE in guinea pigs. For this purpose, the inhibitors of
      endocannabinoid transport, AM404, and enzymatic (fatty acid amide hydrolase)
      degradation, URB597, were applied. Cannabinoid CB1 receptor antagonist, AM251,
      was also tested. Animal behavior as well as local electric field potentials in
      four structures: medial septum, hippocampus, entorhinal cortex and amygdala were
      analyzed when AM404 (120nmol), URB597 (4.8nmol) or AM251 (20nmol) were
      administrated alone or together with 0.4MUg of kainic acid. All substances were
      injected i.c.v. AM404, URB597 or AM251 administered alone did not alter markedly
      local field potentials of all four studied structures in the long-term compared
      with their basal activity. AM404 and URB597 significantly alleviated kainic acid
      induced SE, decreasing behavioral manifestations, duration of seizure events and
      SE in general without changing the amplitude of local field potentials. AM251 did
      not produce distinct effects on SE in terms of our experimental paradigm. There
      was no apparent change of the seizure initiation pattern when kainic acid was
      coadministrated with AM404, URB597 or AM251. The present study provides
      electrophysiologic and behavioral evidences that inhibition of endocannabinoid
      metabolism plays a protective role against kainic acid-induced SE and may be
      employed for therapeutic purposes. Further investigations of the influences of
      cannabinoid-related compounds on SE genesis and especially epileptogenesis are
      required. 

PMID- 25769372
TI  - Semiological and electroencephalographic features of epilepsy with amygdalar
      lesion.
AB  - OBJECTIVE: To identify semiological and scalp/sphenoidal electroencephalographic
      (EEG) features of epilepsy with amygdalar lesion (AL). METHODS: This study
      included 17 patients with epilepsy and distinct AL on MRI, who underwent
      resective surgery. There were nine female and eight male patients with ages at
      surgery ranging from 8 to 48 (mean 26.3) years. Postoperative seizure outcome was
      Engel class I or seizure-free in 12 patients, class II in four, and class III in
      one. Pathological examination revealed dysembryoplastic neuroepithelial tumor in
      eight cases, astrocytoma in two, mixed oligoastrocytoma in three, ganglioglioma
      in two, localized encephalitis in one, and cortical dysplasia in one. Semiology
      and scalp/sphenoidal EEG findings of these patients (AL group) were compared with
      those of 20 mesial temporal lobe epilepsy patients with hippocampal sclerosis
      (HS) who underwent resective surgery with favorable seizure outcome (Engel class
      I) (control group). RESULTS: Increased tonic components during seizure were more
      frequently seen in AL group (58.8%) than in control group (20%). Interictal
      unitemporal slow waves were more frequently found in AL group (58.8%) than in
      control group (20%). Ictal EEG revealed generalized (not only bitemporal) onset
      in six patients in AL group (35.3%), but none in control group. The generalized
      EEG onset patterns in AL group included spike and wave complexes, rhythmic
      spikes, and delta waves. CONCLUSION: Patients with AL had increased tonic
      components during seizure and generalized ictal EEG onset more frequently than
      patients with HS. These findings suggest widespread epileptic network involving
      subcortical structures such as the thalamus and the brainstem in patients with
      AL.

PMID- 25769373
TI  - Hypsarrhythmia paroxysm index: A tool for early prediction of infantile spasms.
AB  - Recurrence of infantile spasms (ISs) is common subsequent to treatment with
      adrenocorticotropic hormone (ACTH) for West syndrome, and prolonged
      hypsarrhythmia results in psychomotor deterioration. The evolution to
      hypsarrhythmia involves conversion of prehypsarrhythmic EEG findings to sporadic
      hypsarrhythmia paroxysms (HPs), and when paroxysms reach a certain frequency, ISs
      begin to occur. This retrospective chart study aimed to determine the HP
      threshold frequency after which ISs begin. Recorded either prior (Group A) or
      subsequent (Group B) to IS relapse, 248 EEGs were examined in 42 patients. The
      number of HPs in non-rapid eye movement (NREM) sleep divided by NREM duration
      constituted the countable hypsarrhythmia paroxysms index (cHPI). After reaching a
      rate of approximately 10/min, the cHPI lost its feasibility due to the merging of
      HPs. The durational HPI (dHPI) was also calculated (total duration of HPs during
      NREM/NREM sleep time*100). ACTH treatment was administered if cHPI was >=2/min,
      with the aim of preventing relapse. The mean cHPI value without a concomitant
      spasm relapse (in Group A) was 1.20/min. Following relapse, this value rose to
      4.10/min. EEGs performed subsequent to relapse (in Group B) were classified into
      three subgroups (B1, B2, and B3) according to the duration of the time interval
      between IS relapse and the succeeding EEG recording. One-way analysis of variance
      (ANOVA) indicated that cHPI values differed significantly between the Group B
      subgroups. In subgroups B2 and B3, a higher number of EEGs were evaluated via
      dHPI. Linear regression analysis established that the interval between recurrence
      and the succeeding EEG recording significantly predicted cHPI values and
      accounted for 54.2% of the explained variability in cHPI values. Therefore, use
      of the cHPI for early recognition and intervention may aid in preventing the
      onset and recurrence of ISs and further deterioration of psychomotor development.

PMID- 25769374
TI  - Widespread inter-ictal excitability changes in patients with temporal lobe
      epilepsy: A TMS/MEG study.
AB  - PURPOSE: Transcranial magnetic stimulation (TMS) has been used to elucidate the
      altered balance between excitatory and inhibitory circuits in the motor cortex in
      epilepsy; however, TMS could not well assess excitability changes beyond the
      motor cortex. This study aimed to address the spatial profile of cortical
      excitability changes in patients with temporal lobe epilepsy (TLE) by using TMS
      and magnetoencephalography (MEG). METHODS: Eighteen patients with TLE and 18
      healthy control subjects were recruited. Resting motor threshold (RMT) and
      intracortical inhibition (ICI) were measured to reflect motor cortical
      excitability by using TMS. A whole-head MEG was applied to record auditory and
      somatosensory evoked responses to paired-pulse stimuli. A paired-pulse inhibition
      (PPI) ratio, defined as the amplitude ratio between responses to the second and
      the first stimuli, was used to assess the auditory and somatosensory cortical
      excitability. A high PPI ratio suggests an increase in cortical excitability,
      while a low ratio indicates a decrease in excitability. RESULTS: Compared to
      control subjects, TLE patients exhibited increased RMT in motor cortex and higher
      PPI ratios for auditory P50m and somatosensory P35m responses. Notably, patients
      with a lower seizure frequency tended to exhibit a higher RMT or a lower P35m PPI
      ratio. CONCLUSIONS: Present data suggest that the cortical excitability
      alteration in focal epilepsy is widely distributed beyond the epileptic focus and
      the profiles of excitability change correlate with clinical severity in terms of
      seizure frequency. Combined MEG and TMS studies provide new insight into the
      inter-ictal cortical excitability profiles in patients with epilepsy.

PMID- 25769375
TI  - Homozygous TBC1D24 mutation in two siblings with familial infantile myoclonic
      epilepsy (FIME) and moderate intellectual disability.
AB  - Mutations in the TBC1D24 gene were first reported in an Italian family with a
      unique epileptic phenotype consisting of drug-responsive, early-onset idiopathic
      myoclonic seizures. Patients presented with isolated bilateral or focal
      myoclonia, which could evolve to long-lasting attacks without loss of
      consciousness, with a peculiar reflex component, and were associated with
      generalized tonic-clonic seizures. This entity was named "familial infantile
      myoclonic epilepsy" (FIME). More recently, TBC1D24 mutations have been shown to
      cause a variable range of disorders, including epilepsy of various seizure types
      and severity, non-syndromic deafness, and DOORS syndrome. We report on the
      electro-clinical features of two brothers, born to first-cousin parents, affected
      with infantile-onset myoclonic epilepsy. The peculiar epileptic presentation
      prompted us to perform direct sequencing of the TBC1D24 gene. The patients had
      very early onset of focal myoclonic fits with variable topography, lasting a few
      minutes to several hours, without loss of consciousness, which frequently evolved
      to generalized myoclonus or myoclonic status. Reflex myoclonia were noticed in
      one patient. Neurological outcome was marked by moderate intellectual disability.
      Despite the high frequency of seizures, repeated EEG recordings showed normal
      background rhythm and rare interictal spikes and waves. We found a homozygous
      missense mutation, c.457G>A/p.Glu153Lys, in the two affected brothers. This
      observation combined with recent data from the literature, suggest that mutations
      in TBCD24 cause a pathological continuum, with FIME at the "benign" end and
      severe drug-refractory epileptic encephalopathy on the severe end. Early-onset
      myoclonic epilepsy with focal and generalized myoclonic seizures is a common
      characteristic of this continuum. 

PMID- 25769376
TI  - Reduced cortical activation in inferior frontal junction in Unverricht-Lundborg
      disease (EPM1) - A motor fMRI study.
AB  - BACKGROUND: Unverricht-Lundborg disease (EPM1) is characterized by stimulus
      sensitive and action-activated myoclonus, tonic-clonic seizures and ataxia.
      Several disease-related alterations in cortical structure and excitability have
      been associated with the motor symptoms of EPM1. This study aimed to elucidate
      possible alterations in cortical activation related to motor performance in EPM1.
      METHODS: Fifteen EPM1-patients and 15 healthy volunteers matched for age and sex
      underwent motor functional MRI. Group differences in activations were evaluated
      in the primary and supplementary motor cortices and sensory cortical areas.
      Furthermore, in EPM1 patients, the quantitative fMRI parameters were correlated
      with the severity of the motor symptoms. RESULTS: The EPM1-patients exhibited
      decreased activation in the left inferior frontal junction (IFJ) during right
      hand voluntary motor task when compared with controls. In the quantitative
      analysis, EPM1-patients had significantly weaker activation than controls in the
      hand knob and supplementary motor areas (SMA). The volume of activation in M1
      decreased with age and duration of disease in the patient group, whereas the
      volume increased with age in controls. Negative correlations were observed
      between fMRI parameters of SMA and disease duration or age in patients but not in
      controls. CONCLUSIONS: The weaker motor fMRI activation observed in EPM1 patients
      parallels previous neurophysiological findings and correlates with the motor
      symptoms of the disease. Thus, the observed decrease in IFJ activation in EPM1
      patients may be associated with the difficulties in initiation or termination of
      motor execution, a typical clinical symptom in EPM1. The fMRI findings reflect
      the progressive nature of this disease.

PMID- 25769377
TI  - Progress report on new antiepileptic drugs: A summary of the Twelfth Eilat
      Conference (EILAT XII).
AB  - The Twelfth Eilat Conference on New Antiepileptic Drugs (AEDs) - EILAT XII, took
      place in Madrid, Spain from August 31st to September 3rd 2014. About 130 basic
      scientists, clinical pharmacologists and neurologists from 22 countries attended
      the conference, whose main themes included "Conquering pharmacoresistant
      epilepsy", "Innovative emergency treatments", "Progress report on second
      generation treatment" and "New methods and formulations". Consistent with
      previous formats of this conference, a large part of the program was devoted to a
      review of AEDs in development, as well as updates on AEDs introduced since 2004.
      Like the EILAT X and EILAT XI reports, the current article focuses on the
      preclinical and clinical pharmacology of AEDs that are currently in development.
      These include adenosine-releasing silk, allopregnanolone (SAGE-547), AMP-X-0079,
      brivaracetam, bumetanide, cannabidiol, cannabidivarin, 2-deoxy-glucose,
      everolimus, ganaxolone, huperzine A, imepitoin, minocycline, NAX 801-2,
      pitolisant, PRX 0023, SAGE-217, valnoctamide and its homologue sec-butyl
      propylacetamide (SPD), and VLB-01. Since the previous Eilat conference,
      perampanel has been introduced into the market and twelve novel potential
      epilepsy treatments are presented for the first time. 

PMID- 25769378
TI  - Effects of neonatal hypoxic-ischemic episodes on late seizure outcomes in C57
      black mice.
AB  - We examined brain injury and seizures in adult C57 black mice (C57/BL6) that
      underwent neonatal hypoxic-ischemic (HI) episodes. Mouse pups of 7 days-old
      underwent a ligation of the right common carotid artery and a subsequent hypoxic
      challenge (8% O2 for 45min). Post-HI mice were implanted with intracranial
      electrodes at 2-3 months of age, subjected to behavioral/EEG recordings and
      hippocampal electrical stimulation in next several months and then euthanized for
      brain histological assessments at ages of 11-12 months. Histological assessment
      revealed ipsilateral brain infarctions in 9 post-HI animals. Evident motor
      seizures were found to occur in only 2 animals with histologically identified
      cystic infarctions but not in the 21 post-HI animals with or without infarctions.
      In response to the hippocampal stimulation, post-HI animals were less prone than
      sham controls to evoked motor seizures. We thus suggest that adult C57 black mice
      may have low propensity of developing epileptic seizures following the neonatal
      HI episode. Our present observations may be relevant to future investigation of
      post-HI epileptogenesis in mouse models. 

PMID- 25769379
TI  - A prospective phase II trial of EGCG in treatment of acute radiation-induced
      esophagitis for stage III lung cancer.
AB  - BACKGROUND: Acute radiation-induced esophagitis (ARIE) is one of main toxicities
      complicated by thoracic radiotherapy, influencing patients' quality of life and
      radiotherapy proceeding seriously. It is difficult to be cured rapidly so far.
      Our phase I trial preliminarily showed that EGCG may be a promising strategy in
      the treatment of ARIE. MATERIALS AND METHODS: We prospectively enrolled patients
      with stage III lung cancer from the Shandong Tumor Hospital & Institute in China
      from January 2013 to September 2014. All patients received concurrent or
      sequential chemo-radiotherapy, or radiotherapy only. EGCG was administrated once
      ARIE appeared. EGCG was given with the concentration of 440MUmol/L during
      radiotherapy and additionally two weeks after radiotherapy. RTOG score, dysphagia
      and pain related to esophagitis were recorded every week. RESULTS: Thirty-seven
      patients with stage IIIA and IIIB lung cancer were enrolled in this trial. In
      comparison to the original, the RTOG score in the 1st, 2nd, 3rd, 4th, 5th week
      after EGCG prescription and the 1st, 2nd week after radiotherapy decreased
      significantly (P=0.002, 0.000, 0.000, 0.001, 0.102, 0.000, 0.000, respectively).
      The pain score of each week was significantly lower than the baseline (P=0.000,
      0.000, 0.000, 0.000, 0.006, 0.000, 0.000, respectively). CONCLUSION: This trial
      confirmed that the oral administration of EGCG is an effective and safe method to
      deal with ARIE. A phase III randomized controlled trial is expected to further
      corroborate the consequence of EGCG in ARIE treatment.

PMID- 25769380
TI  - Low response rate after cetuximab combined with conventional chemoradiotherapy in
      patients with locally advanced anal cancer: long-term results of the UNICANCER
      ACCORD 16 phase II trial.

PMID- 25769381
TI  - [Pulmonary embolism due to a liver hydatid cyst fistulized into the inferior cava
      vein].

PMID- 25769382
TI  - [Spontaneous flash fires during use of alcohol-based hand rubs].

PMID- 25769383
TI  - [Indicator condition guided human immunodeficiency virus requesting in primary
      health care: results of a collaboration].
AB  - INTRODUCTION: The search of HIV infected patients guided by indicator conditions
      (IC) is a strategy used to increase the early detection of HIV. The objective is
      to analyze whether a collaboration to raise awareness of the importance of early
      detection of HIV in 3 primary care centers influenced the proportion of HIV
      serology requested. METHODS: Multicenter retrospective study was conducted
      comparing the baseline and a post-collaboration period. The collaboration
      consisted of training sessions and participation in the HIDES study (years 2009
      2010). Patients between 18 and 64 years old with newly diagnosed herpes zoster,
      seborrheic eczema, mononucleosis syndrome, and leucopenia/thrombocytopenia in 3
      primary care centers in 2008 (baseline period) and 2012 (post-collaboration
      period). The sociodemographic variables, HIV risk conditions, requests for HIV
      serology, and outcomes were evaluated. RESULTS: A total of 1,219 ICs were
      included (558 in 2008 and 661 in 2012). In 2008 the number of HIV tests in
      patients with an IC was 3.9%, and rose to 11.8% in 2012 (P<.0001). The HIV
      infection rate was 2.2% (95% CI: 0.4-7.3) (n=2). It was estimated that 25 new
      cases (12 in 2008 and 13 in 2012) would have been diagnosed if they had performed
      the test on all patients with IC. Predictors of HIV request were, having an IC in
      2012, a younger age, having an mononucleosis syndrome, and not being Spanish.
      CONCLUSIONS: The HIV request demand tripled, after the collaboration with primary
      care centers, however in 88% the test was not requested, resulting in diagnostic
      losses. New strategies are needed to raise awareness of the importance of early
      detection of HIV.

PMID- 25769384
TI  - Augmented telomerase activity, reduced telomere length and the presence of
      alternative lengthening of telomere in renal cell carcinoma: plausible predictive
      and diagnostic markers.
AB  - In this study, we analyzed 100 cases of renal cell carcinoma (RCC) for telomerase
      activity, telomere length and alternative lengthening of telomeres (ALT) using
      the TRAP assay, TeloTTAGGG assay kit and immunohistochemical analysis of ALT
      associated promyelocytic leukemia (PML) bodies respectively. A significantly
      higher (P=0.000) telomerase activity was observed in 81 cases of RCC which was
      correlated with clinicopathological features of tumor for instance, stage
      (P=0.008) and grades (P=0.000) but not with the subtypes of RCC (P = 0.355).
      Notwithstanding, no correlation was found between telomerase activity and
      subtypes of RCC. Strikingly, the telomere length was found to be significantly
      shorter in RCC (P=0.000) to that of corresponding normal renal tissues and it is
      well correlated with grades (P=0.016) but not with stages (P=0.202) and subtypes
      (P=0.669) of RCC. In this study, telomere length was also negatively correlated
      with the age of patients (r(2)=0.528; P=0.000) which supports the notion that it
      could be used as a marker for biological aging. ALT associated PML bodies
      containing PML protein was found in telomerase negative cases of RCC. It suggests
      the presence of an ALT pathway mechanism to maintain the telomere length in
      telomerase negative RCC tissues which was associated with high stages of RCC,
      suggesting a prevalent mechanism for telomere maintenance in high stages. In
      conclusion, the telomerase activity and telomere length can be used as a
      diagnostic as well as a predictive marker in RCC. The prevalence of ALT mechanism
      in high stages of RCC is warranted for the development of anti-ALT inhibitors
      along with telomerase inhibitor against RCC as a therapeutic approach. 

PMID- 25769385
TI  - The association of MC4R rs17782313 polymorphism with dietary intake in Iranian
      adults.
AB  - BACKGROUND: Malfunction in the energy homeostasis system is a major cause of
      developing obesity. Melanocortin-4 receptor (MC4R) plays a crucial role in this
      system as a key receptor. Although MC4R gene as an obesity candidate gene is
      associated with higher BMI, only few attempts have been carried out to understand
      the mechanism underlying body-weight regulation. OBJECTIVE: The aim of this study
      is to investigate the association between variant rs17782313 near MC4R gene and
      both dietary energy and macronutrient intakes. METHODS: An Iranian population,
      400 adults aged over 22years were selected from the Iranian Multicenter
      Osteoporosis Study (IMOS). Genotyping for the near MC4R rs17782313 was performed
      by PCR-RFLP. Weight and height were measured. Dietary intake and physical
      activity were assessed by using validated questionnaires. Analysis was carried
      out in two groups with regard to BMI. Multiple linear regression models adjusted
      for covariates were used to examine the association between rs17782313 and
      dietary intake. RESULTS: MC4R rs17782313 was associated with high energy intake
      (P<0.001), and low carbohydrate and protein intakes (P<0.001 and P<0.01
      respectively). In addition, the significant association between variant
      rs17782313 and fat intake disappeared after adjusting for energy. CONCLUSIONS:
      The rs17782313 variant contributes to the variety of dietary energy and energy
      dense macronutrient intakes. Moreover, a novel association was suggested between
      this polymorphism and dietary fat intake.

PMID- 25769386
TI  - Molecular characterization of 'Candidatus Rickettsia vini' in Ixodes arboricola
      from the Czech Republic and Slovakia.
AB  - The aim of this study was to analyze the prevalence of rickettsiae in the tree
      hole tick Ixodes arboricola in the Czech Republic and Slovakia. During May to
      September of 2009 and 2013, bird boxes belonging to three different areas were
      screened for ticks. In total, 454 nestlings and 109 nests of 10 hole-breeding
      bird species were examined. Ticks were found on Ficedula albicollis, Parus major,
      Cyanistes caeruleus and Sitta europaea and/or in their nests. In total, 166 ticks
      (17 nymphs, 10 males and 139 females) were found at 3 areas (arithmetic mean+/
      standard error: 55.3+/-45.9). All ticks were tested for the presence of
      Rickettsia species by polymerase chain reaction targeting the rickettsial genes
      gltA, ompA, ompB and htrA and amplicon sequencing. All individuals except 3
      nymphs were infected with 'Candidatus Rickettsia vini'. Multilocus sequence
      typing showed closest proximity to Rickettsia japonica and Rickettsia
      heilongjiangensis cluster. The presence of 'Ca. R. vini' is reported for the
      first time in Slovakia. 

PMID- 25769387
TI  - Balloon angioplasty for revision of failing lower extremity bypass grafts.
AB  - OBJECTIVE: The aim of this study was to evaluate the efficacy and safety of
      balloon angioplasty as the primary method of intervention in patients with color
      duplex ultrasound documented failing bypass grafts and to determine factors that
      may affect the patency of lower extremity bypass grafts revised by percutaneous
      transluminal angioplasty (PTA). METHODS: All consecutive patients who underwent
      lower extremity bypass grafts from January 2009 to December 2013 were enrolled in
      a graft surveillance program. Patients identified as having failing grafts
      underwent arteriography to confirm the diagnosis with a view to concomitant
      treatment of the lesion using balloon angioplasty. Procedural success was defined
      as <30% residual stenosis. Treatment failure was defined as target lesion
      restenosis or graft occlusion. Descriptive and life-table analyses were
      performed. RESULTS: PTA was used to revise 96 failing grafts in 90 patients. Mean
      age was 65.8 years (range, 50-88 years), 64% were male, and 66% were symptomatic.
      Mean follow-up was 18.5 months (range, 3-24 months). Twenty-four grafts (25%)
      underwent repeat angioplasty for restenosis. Grafts with multiple lesions (P =
      .009) and grafts aged <6 months from the index operation (P = .004) were the only
      graft-related variables that showed a significant effect on the longevity of the
      endovascular revision. The PTA-revised grafts had primary, assisted primary, and
      secondary patency rates of 56.9%, 83.2%, and 90%, respectively, at 2 years.
      CONCLUSIONS: Primary balloon angioplasty of failing lower extremity bypass
      grafts, notwithstanding the higher restenosis rate and the need for
      reintervention, appears to be safe and is associated with acceptable early and
      medium-term patency rates. Grafts with multiple lesions and those revised <=6
      months of the index operation showed a significant association with the need for
      a second revision at the same site.

PMID- 25769388
TI  - Coronary revascularization induces a shift from cardiac toward noncardiac
      mortality without improving survival in vascular surgery patients.
AB  - OBJECTIVE: Although evidence has shown that ischemic heart disease (IHD) in
      vascular surgery patients has a negative impact on the prognosis after surgery,
      it is unclear whether directed treatment of IHD may influence cause-specific and
      overall mortality. The objective of this study was to determine the prognostic
      implication of coronary revascularization (CR) on overall and cause-specific
      mortality in vascular surgery patients. METHODS: Patients undergoing surgery for
      abdominal aortic aneurysm, carotid artery stenosis, or peripheral artery disease
      in a university hospital in The Netherlands between January 2003 and December
      2011 were retrospectively included. Survival estimates were obtained by Kaplan
      Meier and Cox regression analysis. RESULTS: A total of 1104 patients were
      included. Adjusted survival analyses showed that IHD significantly increased the
      risk of overall mortality (hazard ratio [HR], 1.50; 95% confidence interval, 1.21
      1.87) and cardiovascular death (HR, 1.93; 95% confidence interval, 1.35-2.76).
      Compared with those without CR, patients previously undergoing CR had similar
      overall mortality (HR, 1.38 vs 1.62; P = .274) and cardiovascular mortality (HR,
      1.83 vs 2.02; P = .656). Nonrevascularized IHD patients were more likely to die
      of IHD (6.9% vs 35.7%), whereas revascularized IHD patients more frequently died
      of cardiovascular causes unrelated to IHD (39.1% vs 64.3%; P = .018).
      CONCLUSIONS: This study confirms the significance of IHD for postoperative
      survival of vascular surgery patients. CR was associated with lower IHD-related
      death rates. However, it failed to provide an overall survival benefit because of
      an increased rate of cardiovascular mortality unrelated to IHD. Intensification
      of secondary prevention regimens may be required to prevent this shift toward non
      IHD-related death and thereby improve life expectancy.

PMID- 25769389
TI  - The effect of loss to follow-up on treatment of blunt traumatic thoracic aortic
      injury.
AB  - OBJECTIVE: Loss to follow-up (LTFU) can be a major difficulty for any clinical
      research study. The objective of this systematic review was to assess the extent
      of LTFU and its potential effect in studies of adult trauma patients with blunt
      thoracic aortic injuries (BTAIs). METHODS: Studies comparing management of BTAIs
      were systematically reviewed. Duplicate independent review was used for study
      selection, data abstraction, and critical appraisals. RESULTS: Thirty-six studies
      were included for synthesis, of which 94.1% applied a retrospective cohort design
      to prospective institutional databases. The mean LTFU at 1 year was 26.5% +/-
      31.6% for endovascular repair and 20.6% +/- 34.2% for open repair groups. Not
      having a surgical/interventional specialist as a first or senior author was
      associated with a 39.7% higher LTFU at 1 year (P = .002). Studies with a higher
      risk of bias, later publication year, or North American origin were associated
      with a significantly higher risk for LTFU at 1 year (P <= .001). Nearly half of
      included studies assessed in-hospital outcomes exclusively. Only 38.2% explicitly
      reported LTFU data. Eight studies explicitly described the method of dealing with
      LTFU: eight used survival analysis and one used a national Social Security Death
      Index. Sensitivity analyses using plausible worst-case LTFU scenarios resulted in
      14% to 17% of studies changing direction of effect. CONCLUSIONS: There is
      significant LTFU in trauma studies comparing operative methods for BTAIs. LTFU is
      generally handled and reported suboptimally, and sensitivity analyses suggest
      that study results are sensitive to differential LTFU. This has implications for
      the evidence-based choice of the operative method. Some protective factors that
      may aid in reducing LTFU were identified, one of which was involvement of a
      surgical or interventional specialist as a key author.

PMID- 25769390
TI  - Estimation of brachial artery volume flow by duplex ultrasound imaging predicts
      dialysis access maturation.
AB  - OBJECTIVE: This study validated duplex ultrasound measurement of brachial artery
      volume flow (VF) as predictor of dialysis access flow maturation and successful
      hemodialysis. METHODS: Duplex ultrasound was used to image upper extremity
      dialysis access anatomy and estimate access VF within 1 to 2 weeks of the
      procedure. Correlation of brachial artery VF with dialysis access conduit VF was
      performed using a standardized duplex testing protocol in 75 patients. The
      hemodynamic data were used to develop brachial artery flow velocity criteria
      (peak systolic velocity and end-diastolic velocity) predictive of three VF
      categories: low (<600 mL/min), acceptable (600-800 mL/min), or high (>800
      mL/min). Brachial artery VF was then measured in 148 patients after a primary (n
      = 86) or revised (n = 62) upper extremity dialysis access procedure, and the VF
      category correlated with access maturation or need for revision before
      hemodialysis usage. Access maturation was conferred when brachial artery VF was
      >600 mL/min and conduit imaging indicated successful cannulation based on
      anatomic criteria of conduit diameter >5 mm and skin depth <6 mm. RESULTS:
      Measurements of VF from the brachial artery and access conduit demonstrated a
      high degree of correlation (R(2) = 0.805) for autogenous vein (n = 45; R(2) =
      0.87) and bridge graft (n = 30; R(2) = 0.78) dialysis accesses. Access VF of >800
      mL/min was predicted when the brachial artery lumen diameter was >4.5 mm, peak
      systolic velocity was >150 cm/s, and the diastolic-to-systolic velocity ratio was
      >0.4. Brachial artery velocity spectra indicating VF <800 mL/min was associated
      (P < .0001) with failure of access maturation. Revision was required in 15 of 21
      (71%) accesses with a VF of <600 mL/min, 4 of 40 accesses (10%) with aVF of 600
      to 800 mL/min, and 2 of 87 accesses (2.3%) with an initial VF of >800 mL/min.
      Duplex testing to estimate brachial artery VF and assess the conduit for ease of
      cannulation can be performed in 5 minutes during the initial postoperative
      vascular clinic evaluation. CONCLUSIONS: Estimation of brachial artery VF using
      the duplex ultrasound, termed the "Fast, 5-min Dialysis Duplex Scan," facilitates
      patient evaluation after new or revised upper extremity dialysis access
      procedures. Brachial artery VF correlates with access VF measurements and has the
      advantage of being easier to perform and applicable for forearm and also arm
      dialysis access. When brachial artery velocity spectra criteria confirm a VF >800
      mL/min, flow maturation and successful hemodialysis are predicted if anatomic
      criteria for conduit cannulation are also present.

PMID- 25769391
TI  - Arteriovenous grafts are associated with earlier catheter removal and fewer
      catheter days in the United States Renal Data System population.
AB  - OBJECTIVE: Arteriovenous fistulas (AVFs) are associated with improved long-term
      outcomes but longer maturation times and higher primary failure rates compared
      with arteriovenous grafts (AVGs). The Fistula First Breakthrough Initiative has
      recently emphasized tunneled dialysis catheter (TDC) avoidance. We sought to
      characterize the relationship of AVFs and AVGs to the use of TDCs as well as
      secondary procedures. METHODS: Using the United States Renal Data System (USRDS)
      database, we identified incident hemodialysis (HD) patients in 2005 that started
      HD with a TDC and survived at least 1 year. We then monitored them through 2008.
      Access creation, TDC removal, TDC placement, and secondary procedures were
      identified by Current Procedural Terminology codes (American Medical Association,
      Chicago, Ill). Multivariate logistic regression was used to identify risk factors
      for the primary end points. RESULTS: In 2005, HD was initiated in 56,495
      patients, 74% with a TDC. Of these, 6286 had an access procedure <=3 months and 1
      year of follow-up (AVF, 4634; AVG, 1652). Mean age was 67.7 years (AVF, 67.3;
      AVG, 68.7 years; P < .001), 53.3% were men (AVF, 58.1%; AVG, 40.5%; P < .001),
      and 33.8% were obese (AVF, 33.6%; AVG, 34.4%; P = not significant). AVG placement
      was associated with a higher TDC removal at 1 (7.9% vs 3.1%; P < .001), 3 (47.8%
      vs 17.8%; P < .001), and 6 (60.6% vs 47.2%; P < .001) months. There was no
      difference at 9 months (AVG, 64.9% vs AVF, 62.3%; P = .06). The median time to
      TDC removal was lower in the AVG group (70 days vs 155 days; P < .001).
      Multivariable model found AVFs were associated with decreased odds of TDC removal
      at 3 (odds ratio, 0.22; P < .001) and 6 months (odds ratio, 0.54; P < .001). AVGs
      required more secondary procedures than AVFs at all time points up to 1 year and
      specifically had increased thrombectomy procedures (39.8% vs 11.5%; P < .001).
      CONCLUSIONS: In patients starting dialysis with a TDC, AVGs are associated with
      increased TDC removal and fewer catheter days compared with AVFs at up to 6
      months. However, AVGs require more secondary procedures at all time points up to
      1 year.

PMID- 25769393
TI  - Smoking and potentially preventable hospitalisation: the benefit of smoking
      cessation in older ages.
AB  - AIMS: Reducing preventable hospitalisation is a priority for health systems
      worldwide. This study sought to quantify the contribution of smoking to
      preventable hospitalisation in older adults and the potential benefits of smoking
      cessation. METHODS: Self-reported smoking data for 267,010 Australian men and
      women aged 45+ years linked with administrative hospital data were analysed using
      Cox's models to estimate the effects on risk of hospitalisation for congestive
      heart failure (CHF), diabetes complications, chronic obstructive pulmonary
      disease (COPD) and angina. The impacts of smoking and quitting smoking were also
      quantified using risk advancement periods (RAP). RESULTS: The cohort included 7%
      current smokers, 36% former smokers and 57% never smokers. During an average
      follow-up of 2.7 years, 4% of participants had at least one hospitalisation for
      any of the study conditions (0.8% for CHF, 1.7% for diabetes complications, 0.8%
      for COPD and 1.4% for angina). Compared to never smokers, the adjusted hazard
      ratio for hospitalisation for any of the conditions for current smokers was 1.89
      (95% CI 1.75-2.03), and the RAP was 3.8 years. There were strong dose-response
      relationships between smoking duration, smoking intensity and cumulative smoking
      dose on hospitalisation risk. The excess risk of hospitalisation and RAP for COPD
      was reduced within 5 years of smoking cessation across all age groups, but risk
      reduction for other conditions was only observed after 15 years. CONCLUSION:
      Smoking is associated with increased risk of preventable hospitalisation for
      chronic conditions in older adults and smoking cessation, even at older ages,
      reduces this risk.

PMID- 25769392
TI  - Should pathological gambling and obesity be considered addictive disorders? A
      factor analytic study in a nationally representative sample.
AB  - OBJECTIVE: Pathological gambling (PG) is now aligned with substance use disorders
      in the DSM-5 as the first officially recognized behavioral addiction. There is
      growing interest in examining obesity as an addictive disorder as well. The goal
      of this study was to investigate whether epidemiological data provide support for
      the consideration of PG and obesity as addictive disorders. METHOD: Factor
      analysis of data from a large, nationally representative sample of US adults
      (N=43,093), using nicotine dependence, alcohol dependence, drug dependence, PG
      and obesity as indicators. It was hypothesized that nicotine dependence, alcohol
      dependence and drug use dependence would load on a single factor. It was further
      hypothesized that if PG and obesity were addictive disorders, they would load on
      the same factor as substance use disorders, whereas failure to load on the
      addictive factor would not support their conceptualization as addictive
      disorders. RESULTS: A model with one factor including nicotine dependence,
      alcohol dependence, drug dependence and PG, but not obesity, provided a very good
      fit to the data, as indicated by CFI=0.99, TLI=0.99 and RMSEA=0.01 and loadings
      of all indicators >0.4. CONCLUSION: Data from this study support the inclusion of
      PG in a latent factor with substance use disorders but do not lend support to the
      consideration of obesity, as defined by BMI, as an addictive disorder. Future
      research should investigate whether certain subtypes of obesity are best
      conceptualized as addictive disorders and the shared biological and environmental
      factors that account for the common and specific features of addictive disorders.

PMID- 25769395
TI  - Early post-operative removal of urethral catheter in patients undergoing
      colorectal surgery with epidural analgesia - a prospective pilot clinical study.
AB  - BACKGROUND: Urethral catheter (UC) removal is often delayed following colorectal
      resection due to the perceived increased risk of post-operative urinary retention
      (POUR) in patients with post-operative epidural analgesia (POEA). We aimed to
      determine if UC removal at 48 h, irrespective of ongoing POEA use, altered the
      risk of POUR and other morbidities associated with urethral catheterisation and
      immobility. METHODS: We performed a prospective randomised controlled pilot
      clinical study. Eligible patients were randomised to an experimental arm, SG1 (UC
      removal 48 h post-operatively), or a control arm, SG2 (UC removed following
      cessation of POEA). Rates of POUR, urinary tract infection (UTI), pulmonary
      complications and surgical site infection (SSI) were recorded. Forty-four
      patients were recruited (SG1: n = 22; SG2: n = 22). RESULTS: No females developed
      POUR, while it occurred in three males (20%) in SG1 and 2 males (22.2%) in SG2.
      All patients who developed POUR had undergone rectal resection. Males in SG1 were
      not at significantly increased risk of POUR compared to those in SG2 (R.R 0.875,
      p = 1). No patient developed UTI post-operatively. The rate of pulmonary
      complications (SG1: n = 2; SG2: n = 3, p = 0.229) and SSI (SG1: n = 5; SG2: n =
      2, p = 0.146) were similar between both study arms. DISCUSSION: Males undergoing
      rectal surgery appear to be at increased risk of developing POUR in the presence
      of epidural analgesia, independent of the timing of UC removal. CONCLUSIONS: All
      female patients undergoing colorectal resection and male patients undergoing
      colonic resection may have their urethral catheter removed at 48 h irrespective
      of use of POEA. CLINICAL TRIALS REGISTRATION NUMBER: NCT01508767
      (http://www.clinicaltrials.gov).

PMID- 25769394
TI  - Consequences of impaired purine recycling on the proteome in a cellular model of
      Lesch-Nyhan disease.
AB  - The importance of specific pathways of purine metabolism for normal brain
      function is highlighted by several inherited disorders, such as Lesch-Nyhan
      disease (LND). In this disorder, deficiency of the purine recycling enzyme,
      hypoxanthine-guanine phosphoribosyltransferase (HGprt), causes severe
      neurological and behavioral abnormalities. Despite many years of research, the
      mechanisms linking the defect in purine recycling to the neurobehavioral
      abnormalities remain unclear. In the current studies, an unbiased approach to the
      identification of potential mechanisms was undertaken by examining changes in
      protein expression in a model of HGprt deficiency based on the dopaminergic rat
      PC6-3 line, before and after differentiation with nerve growth factor (NGF).
      Protein expression profiles of 5 mutant sublines carrying different mutations
      affecting HGprt enzyme activity were compared to the HGprt-competent parent line
      using the method of stable isotopic labeling by amino acids in cell culture
      (SILAC) followed by denaturing gel electrophoresis with liquid chromatography and
      tandem mass spectrometry (LC-MS/MS) of tryptic digests, and subsequent
      identification of affected biochemical pathways using the Database for
      Annotation, Visualization and Integrated Discovery (DAVID) functional annotation
      chart analysis. The results demonstrate that HGprt deficiency causes broad
      changes in protein expression that depend on whether the cells are differentiated
      or not. Several of the pathways identified reflect predictable consequences of
      defective purine recycling. Other pathways were not anticipated, disclosing
      previously unknown connections with purine metabolism and novel insights into the
      pathogenesis of LND. 

PMID- 25769396
TI  - Hemodynamic and inflammatory responses following transumbilical and transthoracic
      lung wedge resection in a live canine model.
AB  - BACKGROUND: Single-port transumbilical surgery is a well-established platform for
      minimally invasive abdominal surgery. The aim of this study was to compare the
      hemodynamics and inflammatory response of a novel transumbilical technique with
      that of a conventional transthoracic technique in thoracic exploration and lung
      resection in a canine model. METHODS: Sixteen dogs were randomly assigned to
      undergo transumbilical thoracoscopy (n = 8) or standard thoracoscopy (n = 8).
      Animals in the umbilical group received lung resection via a 3-cm transumbilical
      incision in combination with a 2.5-cm transdiaphragmatic incision. Animals in the
      standard thoracoscopy group underwent lung resection via a 3-cm thoracic
      incision. Hemodynamic parameters (e.g., mean arterial pressure, heart rate,
      cardiac index, systemic vascular resistance, and global end-diastolic volume
      index) and inflammatory parameters (e.g., neutrophil count, neutrophil 2',7' 
      dichlorohydrofluorescein [DCFH] expression, monocyte count, monocyte inducible
      nitric oxide synthase expression, total lymphocyte count, CD4+ and CD8+
      lymphocyte counts, the CD4+/CD8+ratio, plasma Creactive protein level,
      interleukin-6 level) were evaluated before surgery, during the operation, and on
      postoperative days 1, 3, 7, and 14. RESULTS: Lung resections were successfully
      performed in all 16 animals. There were 2 surgery-related mortality complications
      (1 animal in each group). In the transumbilical group, 1 death was caused by
      early extubation before the animal fully recovered from the anesthesia. In the
      thoracoscopic group, 1 death was caused by respiratory distress and the
      complication of sepsis at 5 days after surgery. There was no significant
      difference between the two techniques with regard to the hemodynamic and
      immunologic impact of the surgeries. CONCLUSION: This study suggests that the
      hemodynamic and inflammatory changes with endoscopic lung resection performed by
      the transumbilical approach are comparable to those after using the conventional
      transthoracic approach. This information is novel and relevant for surgeons
      interested in developing new surgical techniques in minimally invasive surgery.

PMID- 25769397
TI  - Brain and behavioral evidence for altered social learning mechanisms among women
      with assault-related posttraumatic stress disorder.
AB  - Current neurocircuitry models of PTSD focus on the neural mechanisms that mediate
      hypervigilance for threat and fear inhibition/extinction learning. Less focus has
      been directed towards explaining social deficits and heightened risk of
      revictimization observed among individuals with PTSD related to physical or
      sexual assault. The purpose of the present study was to foster more comprehensive
      theoretical models of PTSD by testing the hypothesis that assault-related PTSD is
      associated with behavioral impairments in a social trust and reciprocity task and
      corresponding alterations in the neural encoding of social learning mechanisms.
      Adult women with assault-related PTSD (n = 25) and control women (n = 15)
      completed a multi-trial trust game outside of the MRI scanner. A subset of these
      participants (15 with PTSD and 14 controls) also completed a social and non
      social reinforcement learning task during 3T fMRI. Brain regions that encoded the
      computationally modeled parameters of value expectation, prediction error, and
      volatility (i.e., uncertainty) were defined and compared between groups. The PTSD
      group demonstrated slower learning rates during the trust game and social
      prediction errors had a lesser impact on subsequent investment decisions. PTSD
      was also associated with greater encoding of negative expected social outcomes in
      perigenual anterior cingulate cortex and bilateral middle frontal gyri, and
      greater encoding of social prediction errors in the left temporoparietal
      junction. These data suggest mechanisms of PTSD-related deficits in social
      functioning and heightened risk for re-victimization in assault victims; however,
      comorbidity in the PTSD group and the lack of a trauma-exposed control group
      temper conclusions about PTSD specifically. 

PMID- 25769398
TI  - Treatment with anti-toxoplasmic activity (TATA) for toxoplasma positive patients
      with bipolar disorders or schizophrenia: a cross-sectional study.
AB  - OBJECTIVE: The association between Toxoplasma gondii seropositivity and
      respectively Bipolar Disorder (BD) and Schizophrenia/Schizoaffective disorder
      (SZ) is one of the most studied link between one pathogen and psychiatric
      disorders. The aim of the present study was thus to retrospectively determine if
      the administration of an antipsychotic and/or a mood stabilizer having known in
      vitro Anti-Toxoplasmic Activity (TATA+) was associated with a better clinical
      outcome in a population of 152 BD or 114 SZ patients and seropositive for T.
      gondii infection compared to patients receiving a treatment without anti
      toxoplasmic activity (TATA-). METHODS: This multicenter study was conducted in an
      academic public hospital during a 3-years period between 2009 and 2011. All
      consecutive inpatients and outpatients with SZ or BD diagnosis with a stable
      treatment for more than 4 weeks were recruited. socio-demographic and clinical
      characteristics measured with validated scales as well as a serological status
      for toxoplasmic infection were included. Treatments were classified according to
      their in vitro antitoxoplasmic activity. A multivariate model was used to
      determine the clinical characteristics that were significantly different between
      patients receiving a treatment with no antitoxoplasmic activity compared to
      others. RESULTS: BD patients with positive serum antibodies against T. gondii
      presented more lifetime depressive episodes (p = 0.048) after adjustment for age,
      sex and sociodemographic characteristics when treated by drug having no anti-toxo
      activity, compared to patients having received drugs with anti-toxo activity. A
      significant difference was not found in BD toxonegative patients and in SZ
      toxopositive or toxonegative patients. CONCLUSIONS: It seems to be of importance
      to consider prescribing a drug with a clear anti-toxoplasmic activity (TATA+) for
      BD patients seropositive to T. gondii, in particular valproate that was found as
      the mood stabilizer with the highest antitoxoplasmic activity. Prospective
      randomized controlled trials are warranted to confirm this preliminary data.

PMID- 25769399
TI  - Author's reply: To PMID 25458169.

PMID- 25769400
TI  - Interventional and surgical therapeutic strategies for pulmonary arterial
      hypertension: Beyond palliative treatments.
AB  - Despite significant advances in pharmacological treatments, pulmonary arterial
      hypertension remains an incurable disease with an unreasonably high morbidity and
      mortality. Although specific pharmacotherapies have shifted the survival curves
      of patients and improved exercise endurance as well as quality of life, it is
      also true that these pharmacological interventions are not always accessible
      (particularly in developing countries) and, perhaps most importantly, not all
      patients respond similarly to these drugs. Furthermore, many patients will
      continue to deteriorate and will eventually require an additional, non
      pharmacological, intervention. In this review we analyze the role of atrial
      septostomy and Potts anastomosis in the management of patients with pulmonary
      arterial hypertension, we summarize the current worldwide clinical experience
      (case reports and case series), and discuss why these interventional/surgical
      strategies might have a therapeutic role beyond that of a "bridge" to
      transplantation. 

PMID- 25769401
TI  - The kinetics of regeneration of rhodopsin under enzyme-limited availability of 11
      cis retinoid.
AB  - In order to describe the regeneration of rhodopsin and the recovery of visual
      sensitivity following exposure of the eye to intense bleaching illumination, two
      models have been proposed, in which there is either a "resistive" or an
      "enzymatic" limit to the supply of retinoid. A solution has previously been
      derived for the resistive model, and here we derive an analytical solution for
      the enzymatic model and we investigate the form of this solution as a function of
      parameter values. We demonstrate that this enzymatic model provides a good fit to
      human post-bleach recovery, for four cases: for rhodopsin regeneration in normal
      subjects; for psychophysical scotopic dark adaptation in normal subjects; for
      rhodopsin regeneration and scotopic dark adaptation in fundus albipunctatus
      patients; and for cone pigment regeneration in normal subjects. Finally, we
      present arguments favouring the enzymatic model as the cellular basis for normal
      human rod and cone pigment regeneration.

PMID- 25769403
TI  - Is excision of the gastric mucosa responsible for the superior outcomes of sleeve
      gastrectomy compared with gastric plication?

PMID- 25769402
TI  - Secondary surgery after sleeve gastrectomy: Roux-en-Y gastric bypass or
      biliopancreatic diversion with duodenal switch.
AB  - BACKGROUND: Laparoscopic sleeve gastrectomy (LSG) has gained popularity as a
      stand-alone procedure with good short-term results for weight loss. However, in
      the long-term, weight regain and other complications are reported. Demand for
      secondary surgery is rising, partly for these reasons. OBJECTIVES: To review the
      indications and effects of secondary surgery, biliopancreatic diversion with
      duodenal switch (BPD/DS) versus laparoscopic Roux-en-Y gastric bypass (LRYGB),
      after LSG. METHODS: Data from all patients who underwent revision of LSG was
      retrospectively analyzed, concerning data on indications for secondary surgery,
      weight loss, and complications. RESULTS: 43 Patients underwent secondary surgery
      after LSG; 25 BPD/DS and 18 LRYGB, respectively. Main indications for secondary
      surgery were inadequate weight loss (n = 17 [40%]) and weight regain (n = 8
      [19%]). For these indications, the median excess weight loss was greater for
      BPD/DS (59% [range 15-113]) compared to LRYGB (23% [range -49-84]) (P = .008)
      after 34 months (range 14-79). In case of dysphagia or gastroesophageal reflux
      disease the complaints resolved after converting to LRYGB. BPD/DS patients were
      more likely to develop a short-term complication and vitamin deficiencies
      compared to LRYGB. CONCLUSIONS: Secondary surgery of LSG to BPD/DS or LRYGB is
      feasible with slightly more complications after BPD/DS. Conversion to LRYGB is
      preferred in cases of dysphagia or gastroesophageal reflux disease. In cases of
      weight regain or insufficient weight loss after LSG, patients had better weight
      loss with a BPD/DS; however, this procedure has the risk of complications, such
      as severe vitamin deficiencies.

PMID- 25769404
TI  - Protein expression of BIRC5, TK1, and TOP2A in malignant peripheral nerve sheath
      tumours--A prognostic test after surgical resection.
AB  - No consensus treatment regime exists beyond surgery for malignant peripheral
      nerve sheath tumours (MPNST), and the purpose of the present study was to find
      new approaches to stratify patients with good and poor prognosis and to better
      guide therapeutic intervention for this aggressive soft tissue cancer. From a
      total of 67 MPNSTs from Scandinavian patients with and without neurofibromatosis
      type 1, 30 MPNSTs were investigated by genome-wide RNA expression profiling and
      63 MPNSTs by immunohistochemical (IHC) analysis, and selected genes were
      submitted to analyses of disease-specific survival. The potential drug target
      genes survivin (BIRC5), thymidine kinase 1 (TK1), and topoisomerase 2-alpha
      (TOP2A), all encoded on chromosome arm 17q, were up-regulated in MPNST as
      compared to benign neurofibromas. Each of them was found to be independent
      prognostic markers on the gene expression level, as well as on the protein level.
      A prognostic profile was identified by combining the nuclear expression scores of
      the three proteins. For patients with completely resected tumours only 15% in the
      high risk group were alive after two years, as compared to 78% in the low risk
      group. In conclusion, we found a novel protein expression profile which
      identifies MPNST patients with inferior prognosis even after assumed curative
      surgery. The tested proteins are drug targets; therefore the expression profile
      may provide predictive information guiding the design of future clinical trials.
      Importantly, as the effect is seen on the protein level using IHC, the biomarker
      panel can be readily implemented in routine clinical testing. 

PMID- 25769406
TI  - Direct RNA-based detection of CTX-M beta-lactamases in human blood samples.
AB  - Bloodstream infections with ESBL-producers are associated with increased
      mortality, which is due to delayed appropriate treatment resulting in clinical
      failure. Current routine diagnostics for detection of bloodstream infections
      consists of blood culture followed by species identification and susceptibility
      testing. In attempts to improve and accelerate diagnostic procedures, PCR-based
      methods have been developed. These methods focus on species identification
      covering only a limited number of ESBL coding genes. Therefore, they fail to
      cover the steadily further evolving genetic diversity of clinically relevant beta
      lactamases. We have recently designed a fast and novel RNA targeting method to
      detect and specify CTX-M alleles from bacterial cultures, based on an
      amplification-pyrosequencing approach. We further developed this assay towards a
      diagnostic tool for clinical use and evaluated its sensitivity and specificity
      when applied directly to human blood samples. An optimized protocol for mRNA
      isolation allows detection of specific CTX-M groups from as little as 100 CFU/mL
      blood via reverse transcription, amplification, and pyrosequencing directly from
      human EDTA blood samples as well as from pre-incubated human blood cultures with
      a turnaround time for test results of <7 h.

PMID- 25769405
TI  - Disulfiram (DSF) acts as a copper ionophore to induce copper-dependent oxidative
      stress and mediate anti-tumor efficacy in inflammatory breast cancer.
AB  - Cancer cells often have increased levels of reactive oxygen species (ROS);
      however, acquisition of redox adaptive mechanisms allows for evasion of ROS
      mediated death. Inflammatory breast cancer (IBC) is a distinct, advanced BC
      subtype characterized by high rates of residual disease and recurrence despite
      advances in multimodality treatment. Using a cellular model of IBC, we identified
      an oxidative stress response (OSR) signature in surviving IBC cells after
      administration of an acute dose of an ROS inducer. Metagene analysis of patient
      samples revealed significantly higher OSR scores in IBC tumor samples compared to
      normal or non-IBC tissues, which may contribute to the poor response of IBC
      tumors to common treatment strategies, which often rely heavily on ROS induction.
      To combat this adaptation, we utilized a potent redox modulator, the FDA-approved
      small molecule Disulfiram (DSF), alone and in combination with copper. DSF forms
      a complex with copper (DSF-Cu) increasing intracellular copper concentration both
      in vitro and in vivo, bypassing the need for membrane transporters. DSF-Cu
      antagonized NFkappaB signaling, aldehyde dehydrogenase activity and antioxidant
      levels, inducing oxidative stress-mediated apoptosis in multiple IBC cellular
      models. In vivo, DSF-Cu significantly inhibited tumor growth without significant
      toxicity, causing apoptosis only in tumor cells. These results indicate that IBC
      tumors are highly redox adapted, which may render them resistant to ROS-inducing
      therapies. DSF, through redox modulation, may be a useful approach to enhance
      chemo- and/or radio-sensitivity for advanced BC subtypes where therapeutic
      resistance is an impediment to durable responses to current standard of care.

PMID- 25769407
TI  - Small plasmids in Streptococcus dysgalactiae subsp. equisimilis isolated from
      human infections in southern India and sequence analysis of two novel plasmids.
AB  - Small plasmids are frequently found in S. pyogenes isolates from human infections
      in India. Streptococcus dysgalactiae subsp. equisimilis (SDSE) is a streptococcal
      subspecies that is genetically similar to S. pyogenes and has a similar ecology.
      Therefore, we determined the distribution of small plasmids in a collection of
      254 SDSE isolates, comprising 44 different emm-types and emm non-typable strains,
      from southern India, utilizing an established PCR based method. Briefly, 1.2%
      (n=3) of the isolates were positive for repA (encoding the replication initiation
      protein A) and 1.6% (n=4) were repB positive (encoding the replication initiation
      protein B). One isolate (G315) showed a co-detection of repB and dysA (encoding
      the bacteriocin dysgalacticin) which is characteristic for previously described
      pDN281/pW2580-like plasmids, observed in SDSE and S. pyogenes. The remaining
      plasmid bearing isolates showed no characteristic co-detection of known plasmid
      associated genes. Thus, plasmids pG271 and pG279, representatives for repB and
      repA harboring plasmids, respectively, were analyzed. The plasmids pG271 and
      pG279 could be assigned to the pMV158 and the pC194/pUB110 family of rolling
      circle plasmids, respectively. Like the characterized small native plasmids of S.
      pyogenes from India, the SDSE plasmids discovered and described in this study did
      not carry any of the known antibiotic resistance genes. SDSE bore less of the
      investigated small native plasmids that were distinct from the small native
      plasmids of S. pyogenes of the same geographic region. This indicates a low rate
      of lateral transfer of these genetic elements between these two related
      streptococcal species. 

PMID- 25769408
TI  - Relationship between stature and tibial length for children with moderate-to
      severe cerebral palsy.
AB  - OBJECTIVE: To derive the equation for estimating stature, based on tibial length,
      for children with moderate-to-severe cerebral palsy (CP) and lower limb joint
      contracture or scoliosis. METHODS: The participants (3-12-years-old) included 50
      children with moderate-to-severe CP (mean age, 8.3+/-2.4 years) and 38 typically
      developed (TD) children (mean age, 7.5+/-2.6 years). Thirty-four (68%) of the
      children with CP had a gross motor function classification system level of V.
      Furthermore, 40 (80%) had definite lower limb joint contracture or scoliosis. The
      stature and the tibial length measurements of all participants were determined.
      Regression equations to estimate stature, based on tibial lengths, were
      determined for both TD children and children with CP. Moreover, regression
      equations defining the relationship between tibial length and age were compared
      between the two groups of children, using multiple regression analysis. RESULTS:
      The regression equations for estimating stature, based on tibial length, were
      stature=tibial length*3.25+34.45 [cm], R(2)=0.91 (TD children), and
      stature=tibial length*3.42+31.82 [cm], R(2)=0.81 (CP children). In children with
      CP, tibial lengths were significantly shorter than those in similarly aged TD
      children. CONCLUSION: The stature of children with moderate-to-severe CP can be
      estimated from their tibial lengths, regardless of the presence of joint
      contracture or scoliosis. The tibial length may be a proxy for estimating stature
      during the growth assessment of children with moderate-to-severe CP.

PMID- 25769409
TI  - Multi-locus fossil-calibrated phylogeny of Atheriniformes (Teleostei,
      Ovalentaria).
AB  - Phylogenetic relationships among families within the order Atheriniformes have
      been difficult to resolve on the basis of morphological evidence. Molecular
      studies so far have been fragmentary and based on a small number taxa and loci.
      In this study, we provide a new phylogenetic hypothesis based on sequence data
      collected for eight molecular markers for a representative sample of 103
      atheriniform species, covering 2/3 of the genera in this order. The phylogeny is
      calibrated with six carefully chosen fossil taxa to provide an explicit timeframe
      for the diversification of this group. Our results support the subdivision of
      Atheriniformes into two suborders (Atherinopsoidei and Atherinoidei), the nesting
      of Notocheirinae within Atherinopsidae, and the monophyly of tribe Menidiini,
      among others. We propose taxonomic changes for Atherinopsoidei, but a few weakly
      supported nodes in our phylogeny suggests that further study is necessary to
      support a revised taxonomy of Atherinoidei. The time-calibrated phylogeny was
      used to infer ancestral habitat reconstructions to explain the current
      distribution of marine and freshwater taxa. Based on these results, the current
      distribution of Atheriniformes is likely due to widespread marine dispersal along
      the margins of continents, infrequent trans-oceanic dispersal, and repeated
      invasion of freshwater habitats. This conclusion is supported by post-Gondwanan
      divergence times among families within the order, and a high probability of a
      marine ancestral habitat. 

PMID- 25769410
TI  - Patients With Roux-en-Y Gastric Bypass Require Increased Sedation During Upper
      Endoscopy.
AB  - BACKGROUND & AIMS: After Roux-en-Y gastric bypass (RYGB), many patients
      experience changes in metabolism that could affect the amount of sedative they
      require. We assessed whether patients who have vs have not received RYGB have
      different sedation requirements during esophagogastroduodenoscopy (EGD). METHODS:
      In a retrospective study, we collected data from patients who had received RYGB
      (n = 200; mean age, 45 years; 188 women; body mass index [BMI], 34.0 +/- 7.1
      kg/m2) or had not (controls, n = 200; mean age, 45 years; 188 women; BMI, 34.1 +/
      7.2 kg/m2) and underwent EGD under conscious sedation from 2005 through 2010;
      groups were matched for age, sex, and BMI. Sedative doses were compared by using
      the Student t test. Multivariate linear regression was used to identify factors
      associated with sedation dose. We performed a subgroup analysis of RYGB patients
      who underwent EGD before and after RYGB, comparing sedative doses with a paired t
      test. RESULTS: Patients with RYGB were given 132.4 +/- 40.4 MUg fentanyl and 5.4
      +/- 1.5 mg midazolam, whereas controls received 108.6 +/- 31.6 MUg fentanyl (P <
      .001) and 4.3 +/- 1.2 mg midazolam (P < .001). Increased time from RYGB, higher
      American Society of Anesthesiologists class, and therapeutic procedure were
      associated with higher doses of sedation (P < .05). Thirty-two patients underwent
      EGD before and after RYGB. Patients were given 95.0 +/- 39.0 MUg fentanyl before
      RYGB and 130.5 +/- 41.3 MUg fentanyl afterward (P < .05); they were given 4.0 +/-
      1.0 mg midazolam before RYGB and 5.5 +/- 1.7 mg midazolam afterward (P < .05).
      CONCLUSIONS: Patients with RYGB require larger amounts of fentanyl and midazolam
      during EGD than patients without RYGB, despite similar age, sex, and BMI. Among
      patients who underwent EGD before and after RYGB, levels of drugs required for
      sedation increased after gastric bypass, despite weight loss.

PMID- 25769411
TI  - The Science, Evidence, and Practice of Dietary Interventions in Irritable Bowel
      Syndrome.
AB  - Irritable bowel syndrome (IBS) is a highly prevalent disorder that is
      characterized by symptoms of abdominal pain, bloating, constipation, and/or
      diarrhea. The diagnosis can be made using Rome III criteria or published
      guidelines after taking a thoughtful history, excluding warning signs, and
      performing a careful physical examination. Limited testing (ie, complete blood
      count and C-reactive protein level) may be useful in appropriate patients. A
      number of pharmacologic options are available, although many patients fail to
      respond to pharmacologic therapy. Although several IBS diets frequently are
      recommended, data supporting their use are limited. This article provides a
      rationale as to why specific diets might improve IBS symptoms and evaluates
      published trials. 

PMID- 25769413
TI  - High Prevalence of Idiopathic Bile Acid Diarrhea Among Patients With Diarrhea
      Predominant Irritable Bowel Syndrome Based on Rome III Criteria.
AB  - BACKGROUND & AIMS: Some studies have found that patients with idiopathic bile
      acid diarrhea (BAD) present with symptoms of diarrhea-predominant irritable bowel
      syndrome (D-IBS). However, these studies either were retrospective, did not
      define D-IBS according to current criteria, or included patients with chronic
      functional diarrhea. We performed a prospective study of the prevalence of
      idiopathic BAD in consecutive patients fulfilling the Rome III criteria for D
      IBS. METHODS: We analyzed data from 118 consecutive adult patients who fulfilled
      the Rome III criteria for D-IBS (mean age, 41.7 y; 72.9% female), seen at 2
      gastroenterology clinics in the United Kingdom. We excluded patients with risk
      factors for BAD (previous history of cholecystectomy, terminal ileal Crohn's
      disease, terminal ileal resection or right hemicolectomy, pelvic or abdominal
      radiotherapy, celiac disease, or microscopic colitis). Participants completed
      questionnaires at baseline (on demographics, hospital anxiety, somatization, and
      depression, as well as the patient health questionnaire-12 and the Short Form
      36), and then received the (75)selenium homocholic acid taurine retention test.
      Retention of (75)selenium homocholic acid taurine 7 days after administration was
      used to identify patients with idiopathic BAD (mild BAD, 10%-14.9%; moderate BAD,
      5.1%-9.9%; and severe BAD, <=5%). RESULTS: Twenty-eight patients were found to
      have BAD (23.7% of total), with similar percentages at each study site (25.3% and
      20%; P = .54). Eight patients had mild BAD (28.6%), 8 patients had moderate BAD
      (28.6%), and 12 patients had severe BAD (42.8%). There was no statistical
      difference in age, sex, depression, patient health questionnaire-12 responses, or
      SF-36 scores between individuals with vs without BAD. However, patients with BAD
      had a higher mean body mass index than patients without BAD (31.6 vs 26.4; P =
      .003). Physical activity (based on the Short Form-36) was significantly lower in
      subjects with moderate (43.8) or severe BAD (41.7), compared with patients with
      mild BAD (87.5) (P = .046). CONCLUSIONS: Almost 25% of patients presenting with D
      IBS have idiopathic BAD; most cases are moderate to severe. Guidelines should
      advocate testing to exclude BAD before patients are diagnosed with D-IBS.

PMID- 25769412
TI  - Differences in Weight Loss Between Persons on Standard Balanced vs Nutrigenetic
      Diets in a Randomized Controlled Trial.
AB  - BACKGROUND & AIMS: Many companies provide genetic tests for obesity-related
      polymorphisms (nutrigenetics) and make dietary recommendations for weight loss
      that are based on the results. We performed a randomized controlled trial to
      determine whether more participants who followed a nutrigenetic-guided diet lost
      >=5% of their body weight than participants on a standard balanced diet for 8 and
      24 weeks. METHODS: We performed a prospective study of 51 obese or overweight
      U.S. veterans on an established weight management program at the Veterans
      Administration San Diego Healthcare System (the MOVE! program). Participants were
      randomly assigned to groups placed on a nutrigenetic-guided diet (balanced, low
      carbohydrate, low-fat, or Mediterranean; n = 30) or a standard balanced diet (n =
      21). Nutrigenetic diets were selected on the basis of results from the Pathway
      FIT test. RESULTS: There was no significant difference in the percentage of
      participants on the balanced diet vs the nutrigenetic-guided diet who lost 5% of
      their body weight at 8 weeks (35.0% +/- 20.9% vs 26.9% +/- 17.1%, respectively; P
      = .28) or at 24 weeks. Both groups had difficulty adhering to the diets. However,
      adherence to the nutrigenetic-guided diet correlated with weight loss (r = 0.74;
      P = 4.0 * 10(-5)), but not adherence to standard therapy (r = 0.34; P = .23).
      Participants who had low-risk polymorphisms for obesity lost more weight than all
      other participants at 8 weeks (5.0% vs 2.9%, respectively; P = .02) and had
      significantly greater reductions in body mass index (6.4% vs 3.6%, respectively;
      P = .03) and waist circumference (6.5% vs 2.6%, respectively; P = .02) at 24
      weeks. CONCLUSIONS: In a prospective study, a nutrigenetic-based diet did not
      increase weight loss compared with a standard balanced diet. However, genetic
      features can identify individuals most likely to benefit from a balanced diet
      weight loss strategy; these findings require further investigation.
      ClinicalTrials.gov number: NCT01859403.

PMID- 25769414
TI  - An interaction map of small-molecule kinase inhibitors with anaplastic lymphoma
      kinase (ALK) mutants in ALK-positive non-small cell lung cancer.
AB  - Human anaplastic lymphoma kinase (ALK) has become a well-established target for
      the treatment of ALK-positive non-small cell lung cancer (NSCLC). Here, we have
      profiled seven small-molecule inhibitors, including 2 that are approved drugs,
      against a panel of clinically relevant mutations in ALK tyrosine kinase (TK)
      domain, aiming at a comprehensive understanding of molecular mechanism and
      biological implication underlying inhibitor response to ALK TK mutation. We find
      that (i) the gatekeeper mutation L1196M causes crizotinib resistance by
      simultaneously increasing and decreasing the binding affinities of, respectively,
      ATP and inhibitor to ALK, whereas the secondary mutation C1156Y, which is located
      far away from the ATP-binding site of ALK TK domain, causes the resistance by
      inducing marked allosteric effect on the site, (ii) the 2nd and 3rd generation
      kinase inhibitors exhibit relatively high sensitivity towards ALK mutants as
      compared to 1st generation inhibitors, (iii) the pan-kinase inhibitor
      staurosporine is insensitive for most mutations due to its high structural
      compatibility, and (iv) ATP affinity to ALK is generally reduced upon most
      clinically relevant mutations. Furthermore, we also identify six novel mutation
      inhibitor pairs that are potentially associated with drug resistance. In
      addition, the G1202R and C1156Y mutations are expected to generally cause
      resistance for many existing inhibitors, since they can address significant
      effect on the geometric shape and physicochemical property of ALK active pocket. 

PMID- 25769415
TI  - PPIase is associated with the diversity of conotoxins from cone snail venom
      glands.
AB  - Cone snails are incredibly rich sources of bioactive conopeptides with potential
      for use in neuroscience research and novel drug development. In order to
      investigate the synthesis of diversified conopeptides in venom glands, the
      proteome and peptidome profiles of conus venom were analyzed using HPLC and mass
      spectrometry. The peptidome profile of the venom components with a molecular
      weight under 10 kDa showed that the peptides with unique mass values from the
      venom glands of Conus caracteristicus, Conus lividus and Conus textile are 188,
      413 and 265, respectively, and there are 39 overlapping peptides among the three
      species. Proteome profiling of the components with molecular weights above 10 kDa
      showed that the most abundant proteins (38.6%) are involved in metabolism and
      that approximately 6.8% of proteins are involved in protein synthesis, folding
      and post-translational modification. Among these proteins, PPIase is one protein
      identified from C. textile based on proteomic analysis. Conus PPIase was
      successfully expressed as a fusion protein with TRX in an Escherichia coli
      expression system for further function study. In-vitro enzyme activity assays
      showed that cone snail PPIase could induce the cis-trans isomerization of the
      substrate succinyl-Ala-Ala-Pro-Phe-p-nitroanilide. The HPLC mapping analyses of
      linear lt14a, a conotoxin with 3 prolines, showed that different lt14a isoforms
      appear after incubation with PPIase. Our results suggest that PPIase may modify
      conotoxins containing prolines and play an important role in the process of
      peptide folding and modification in venom glands and contribute to conotoxin
      diversity. 

PMID- 25769416
TI  - Long noncoding RNA turnover.
AB  - Most RNAs transcribed in mammalian cells lack protein-coding sequences. Among
      them is a vast family of long (>200 nt) noncoding (lnc)RNAs. LncRNAs can modulate
      cellular protein expression patterns by influencing the transcription of many
      genes, the post-transcriptional fate of mRNAs and ncRNAs, and the turnover and
      localization of proteins. Given the broad impact of lncRNAs on gene regulation,
      there is escalating interest in elucidating the mechanisms that govern the steady
      state levels of lncRNAs. In this review, we summarize our current knowledge of
      the factors and mechanisms that modulate mammalian lncRNA stability. 

PMID- 25769418
TI  - Targeted label-free approach for quantification of epoxide hydrolase and
      glutathione transferases in microsomes.
AB  - The aim of this study was to investigate the expression and organ distribution of
      cytochrome P450 (CYP450) enzymes, microsomal epoxide hydrolase (MEH), and
      microsomal glutathione-S-transferase (MGST 1, 2, 3) in human liver, lung,
      intestinal, and kidney microsomes by targeted peptide-based quantification using
      nano liquid chromatography-tandem multiple reaction monitoring (nano LC-MRM).
      Applying this method, we analyzed 16 human liver microsomes and pooled lung,
      kidney, and intestine microsomes. Nine of the CYP450s (CYP1A2, 2B6, 2C8, 2C9,
      2C19, 2D6, 2E1, 3A4, 3A5) could be quantified in liver. Except for CYP3A4 and 3A5
      existing in intestine, other CYP450s had little content (<0.1 pmol/mg protein) in
      extrahepatic tissues. MEH and MGSTs could be quantified both in hepatic and in
      extrahepatic tissues. The highest concentrations of MEH and MGST 1, 2 were found
      in liver; conversely MGST 3 was abundant in human kidney and intestine compared
      to liver. The targeted proteomics assay described here can be broadly and
      efficiently utilized as a tool for investigating the targeted proteins. The
      method also provides novel CYP450s, MEH, and MGSTs expression data in human
      hepatic and extrahepatic tissues that will benefit rational approaches to
      evaluate metabolism in drug development.

PMID- 25769417
TI  - Isolation and cytokine analysis of lamina propria lymphocytes from mucosal
      biopsies of the human colon.
AB  - Much of our understanding of gut-microbial interactions has come from mouse
      models. Intestinal immunity is complex and a combination of host genetics and
      environmental factors play a significant role in regulating intestinal immunity.
      Due to this complexity, no mouse model to date gives a complete and accurate
      representation of human intestinal diseases, such as inflammatory bowel diseases.
      However, intestinal tissue from patients undergoing bowel resection reflects a
      condition of severe disease that has failed treatment; hence a more dynamic
      perspective of varying inflammatory states in IBD could be obtained through the
      analyses of pinch biopsy material. Here we describe our protocol for analyzing
      mucosal pinch biopsies collected predominantly during colonoscopies. We have
      optimized flow cytometry panels to analyze up to 8 cytokines produced by CD4+ and
      CD8+ cells, as well as for characterizing nuclear proteins and transcription
      factors such as Ki67 and Foxp3. Furthermore, we have optimized approaches to
      analyze the production of cytokines, including TGF-beta from direct ex vivo
      cultures of pinch biopsies and LPMCs isolated from biopsies. These approaches are
      part of our workflow to try and understand the role of the gut microbiota in
      complex and dynamic human intestinal diseases. 

PMID- 25769419
TI  - Improved Fab presentation on phage surface with the use of molecular chaperone
      coplasmid system.
AB  - The low presentation efficiency of Fab (fragment antigen binding) fragments
      during phage display is largely due to the complexity of disulphide bond
      formation. This can result in the presentation of Fab fragments devoid of a light
      chain during phage display. Here we propose the use of a coplasmid system
      encoding several molecular chaperones (DsbA, DsbC, FkpA, and SurA) to improve Fab
      packaging. A comparison was done using the Fab fragment from IgG and IgD. We
      found that the use of the coplasmid during phage packaging was able to improve
      the presentation efficiency of the Fab fragment on phage surfaces. A modified
      version of panning using the coplasmid system was evaluated and was successful at
      enriching Fab binders. Therefore, the coplasmid system would be an attractive
      alternative for improved Fab presentation for phage display. 

PMID- 25769420
TI  - Evaluating the effects of preanalytical variables on the stability of the human
      plasma proteome.
AB  - High quality clinical biospecimens are vital for biomarker discovery,
      verification, and validation. Variations in blood processing and handling can
      affect protein abundances and assay reliability. Using an untargeted LC-MS
      approach, we systematically measured the impact of preanalytical variables on the
      plasma proteome. Time prior to processing was the only variable that affected the
      plasma protein levels. LC-MS quantification showed that preprocessing times <6h
      had minimal effects on the immunodepleted plasma proteome, but by 4 days
      significant changes were apparent. Elevated levels of many proteins were
      observed, suggesting that in addition to proteolytic degradation during the
      preanalytical phase, changes in protein structure are also important
      considerations for protocols using antibody depletion. As to processing
      variables, a comparison of single- vs double-spun plasma showed minimal
      differences. After processing, the impact ?3 freeze-thaw cycles was negligible
      regardless of whether freshly collected samples were processed in short
      succession or the cycles occurred during 14-17 years of frozen storage (-80 
      degrees C). Thus, clinical workflows that necessitate modest delays in blood
      processing times or employ different centrifugation steps can yield valuable
      samples for biomarker discovery and verification studies.

PMID- 25769422
TI  - Folding upon phosphorylation: translational regulation by a disorder-to-order
      transition.
AB  - 4E binding proteins (4E-BPs) play an important role in the regulation of
      translation by binding to eukaryotic translation initiation factor 4E (eIF4E) and
      inhibiting assembly of the eIF4F complex. While phosphorylation of 4E-BPs is
      known to disrupt their binding to eIF4E, the mechanism by which this occurs has
      been unclear. In a recent study, Forman-Kay and coworkers demonstrate that this
      mechanism is primarily structure-based: phosphorylation of 4E-BPs results in a
      disorder-to-order transition, bringing them from their binding-competent
      disordered state to a folded state incompatible with eIF4E binding. 

PMID- 25769421
TI  - Mass-spectrometric profiling of porphyrins in complex biological samples with
      fundamental, toxicological, and pharmacological applications.
AB  - Rapid, high-throughput, and quantitative evaluations of biological metabolites in
      complex milieu are increasingly required for biochemical, toxicological,
      pharmacological, and environmental analyses. They are also essential for the
      development, testing, and improvement of new commercial chemical products. We
      demonstrate the application of ultra-high performance liquid chromatography-mass
      spectrometry (uHPLC-MS), employing an electrospray ionization source and a high
      accuracy quadrupole time-of-flight mass analyzer, for the identification and
      quantification of a series of porphyrin derivatives in liver: a matrix of
      particular relevance in toxicological or pharmacological testing. Exact mass is
      used to identify and quantify the metabolites. Chromatography enhances
      sensitivity and alleviates potential saturation issues by fanning out the
      contents of a complex sample before their injection into the spectrometer, but is
      not strictly necessary for the analysis. Extraction and sample treatment
      procedures are evaluated and matrix effects discussed. Using this method, the
      known mechanism of action of a well-characterized porphyrinogenic agent was
      verified in liver extracts from treated rats. The method was also validated for
      use with bacterial cells. This exact-mass method uses workhorse instruments
      available in many laboratories, providing a highly flexible alternative to
      existing HPLC- and MS/MS-based approaches for the simultaneous analysis of
      multiple compounds in biological media. 

PMID- 25769423
TI  - Axon guidance proteins in neurological disorders.
AB  - Many neurological disorders are characterised by structural changes in neuronal
      connections, ranging from presymptomatic synaptic changes to the loss or rewiring
      of entire axon bundles. The molecular mechanisms that underlie this perturbed
      connectivity are poorly understood, but recent studies suggest a role for axon
      guidance proteins. Axon guidance proteins guide growing axons during development
      and control structural plasticity of synaptic connections in adults. Changes in
      expression or function of these proteins might induce pathological changes in
      neural circuits that predispose to, or cause, neurological diseases. For some
      neurological disorders, such as midline crossing disorders, investigators have
      identified causative mutations in genes for axon guidance. However, for most
      other disorders, evidence is correlative and further studies are needed to
      confirm the pathological role of defects in proteins for axon guidance.
      Importantly, further insight into how dysregulation of axon guidance proteins
      causes disease will help the development of therapeutic strategies for
      neurological disorders. 

PMID- 25769424
TI  - Examining the neuroprotective effects of protocatechuic acid and chrysin on in
      vitro and in vivo models of Parkinson disease.
AB  - Polypharmacology-based strategies using drug combinations with different
      mechanisms of action are gaining increasing attention as a novel methodology to
      discover potentially innovative medicines for neurodegenerative disorders. We
      used this approach to examine the combined neuroprotective effects of two
      polyphenols, protocatechuic acid (PCA) and chrysin, identified from the fruits of
      Alpinia oxyphylla. Our results demonstrated synergistic neuroprotective effects,
      with chrysin enhancing the protective effects of PCA, resulting in greater cell
      viability and decreased lactate dehydrogenase release from 6-hydroxydopamine
      treated PC12 cells. Their combination also significantly attenuated chemically
      induced dopaminergic neuron loss in both zebrafish and mice. We examined the
      molecular mechanisms underlying these collective cytoprotective effects through
      proteomic analysis of treated PC12 cells, resulting in the identification of 12
      regulated proteins. Two were further characterized, leading to the determination
      that pretreatment with PCA and chrysin resulted in (i) increased nuclear factor
      erythroid 2-related factor 2 protein expression and transcriptional activity;
      (ii) modulation of cellular redox status with the upregulated expression of
      hallmark antioxidant enzymes, including heme oxygenase-1, superoxide dismutase,
      and catalase; and (iii) decreased levels of malondialdehyde, a known lipid
      peroxidation product. Treatment with PCA and chrysin also inhibited activation of
      nuclear factor-kappaB and expression of inducible nitric oxide synthase. Our
      findings suggest that natural products, when used in combination, can be
      effective potential therapeutic agents for treating diseases such as Parkinson
      disease. A therapy involving both PCA and chrysin exhibits its enhanced
      neuroprotective effects through a combination of cellular mechanisms: antioxidant
      cytoprotection and anti-inflammation. 

PMID- 25769425
TI  - Comorbid psychiatric diagnosis and psychological correlates of eating disorders
      in dance students.
AB  - BACKGROUND/PURPOSE: Although dancers are at risk for eating disorders (EDs),
      little is known about the features of EDs among the dance population. This study
      explores the prevalence of EDs, and their psychiatric comorbidities and
      correlates in dance students. METHODS: In total, 442 female high-school dance
      students participated in a two-phase survey. All participants completed screening
      questionnaires as well as measures assessing teasing, self-esteem, perfectionism,
      body dissatisfaction, and personality. Of the participating students, 311
      underwent the Structured Clinical Interview for DSM-IV-TR Axis I Disorders.
      RESULTS: Sixty-eight individuals (15.4%) had an ED by DSM-IV diagnosis. The
      prevalence of any co-occurring mood (47.1%) and anxiety disorders (30.9%) was
      high. Although low self-esteem, high neuroticism, and high psychological distress
      were associated with EDs in univariate analysis, only teasing for overweight and
      body image dissatisfaction were significantly associated with EDs by multivariate
      analysis. CONCLUSION: Prevention and intervention programs for dance students
      should include recognition and management of emotional disorders and strategies
      promoting positive body image and reducing the incidence of negative weight
      related comments.

PMID- 25769426
TI  - Severe fever with thrombocytopenia syndrome: a newly discovered emerging
      infectious disease.
AB  - Severe fever with thrombocytopenia syndrome (SFTS) is a newly discovered emerging
      infectious disease that has recently become epidemic in Asia. The causative agent
      of SFTS is a novel phlebovirus in the family Bunyaviridae, designated SFTS virus
      (SFTSV). SFTS clinically presents with high fever, thrombocytopenia,
      leukocytopenia, gastrointestinal disorders, and multi-organ dysfunction, with a
      high viral load and a high case-fatality rate. In human infection, SFTSV targets
      microphages, replicates in the spleen of infected mice, and causes
      thrombocytopenia and a cytokine storm. The tick disseminates virus to humans and
      animals, forming a special transmission model in nature. Person-to-person
      transmission though direct contact with patient blood has been frequently
      reported. Measurements of viral RNA and antibodies have been established for
      diagnosis, but vaccines and specific therapeutics are not available so far. 

PMID- 25769427
TI  - Therapy of acute gastroenteritis: role of antibiotics.
AB  - Acute infectious diarrhoea remains a very common health problem, even in the
      industrialized world. One of the dilemmas in assessing patients with acute
      diarrhoea is deciding when to test for aetiological agents and when to initiate
      antimicrobial therapy. The management and therapy of acute gastroenteritis is
      discussed in two epidemiological settings: community-acquired diarrhoea and
      travellers' diarrhoea. Antibiotic therapy is not required in most patients with
      acute gastroenteritis, because the illness is usually self-limiting.
      Antimicrobial therapy can also lead to adverse events, and unnecessary treatments
      add to resistance development. Nevertheless, empirical antimicrobial therapy can
      be necessary in certain situations, such as patients with febrile diarrhoeal
      illness, with fever and bloody diarrhoea, symptoms persisting for >1 week, or
      immunocompromised status.

PMID- 25769428
TI  - Viral and vector zoonotic exploitation of a homo-sociome memetic complex.
AB  - As most newly characterized emerging infectious diseases are considered to be
      zoonotic, a modern pre-eminence ascribed within this classification lies clearly
      within the viral taxonomic realm. In particular, RNA viruses deserve special
      concern given their documented impact on conservation biology, veterinary
      medicine and public health, with an unprecedented ability to promote an
      evolutionary host-pathogen arms race from the ultimate infection and immunity
      perspective. However, besides the requisite molecular/gross anatomical and
      physiological bases for infectious diseases to transmit from one host to another,
      both viral pathogens and their reservoirs/vectors exploit a complex
      anthropological, cultural, historical, psychological and social suite that
      specifically defines the phylodynamics within Homo sapiens, unlike any other
      species. Some of these variables include the ecological benefits of living in
      groups, decisions on hunting and foraging behaviours and dietary preferences,
      myths and religious doctrines, health economics, travel destinations, population
      planning, political decisions on agricultural product bans and many others, in a
      homo-sociome memetic complex. Taken to an extreme, such complexities elucidate
      the underpinnings of explanations as to why certain viral zoonoses reside in
      neglected people, places and things, whereas others are chosen selectively and
      prioritized for active mitigation. Canine-transmitted rabies serves as one prime
      example of how a neglected viral zoonosis may transition to greater attention on
      the basis of renewed advocacy, social media, local champions and vested
      international community engagement. In contrast, certain bat-associated and
      arboviral diseases suffer from basic ignorance and perpetuated misunderstanding
      of fundamental reservoir and vector ecology tenets, translated into failed
      control policies that only exacerbate the underlying environmental conditions of
      concern. Beyond applied biomedical knowledge, epidemiological skills and
      biotechnical abilities alone, if a homo-sociome memetic complex approach is also
      entertained in a modern transdisciplinary context, neglected viral zoonosis may
      be better understood, controlled, prevented and possibly eliminated, in a more
      holistic One Health context. 

PMID- 25769429
TI  - Neglected fungal zoonoses: hidden threats to man and animals.
AB  - Zoonotic fungi can be naturally transmitted between animals and humans, and in
      some cases cause significant public health problems. A number of mycoses
      associated with zoonotic transmission are among the group of the most common
      fungal diseases, worldwide. It is, however, notable that some fungal diseases
      with zoonotic potential have lacked adequate attention in international public
      health efforts, leading to insufficient attention on their preventive strategies.
      This review aims to highlight some mycoses whose zoonotic potential received less
      attention, including infections caused by Talaromyces (Penicillium) marneffei,
      Lacazia loboi, Emmonsia spp., Basidiobolus ranarum, Conidiobolus spp. and
      Paracoccidioides brasiliensis. 

PMID- 25769430
TI  - Smad4 Decreases the Population of Pancreatic Cancer-Initiating Cells through
      Transcriptional Repression of ALDH1A1.
AB  - Cancer progression involves a rare population of undifferentiated cancer
      initiating cells that have stem cell-like properties for self-renewal capacity
      and high tumorigenicity. We investigated how maintenance of pancreatic cancer
      initiating cells is influenced by Smad4, which is frequently deleted or mutated
      in pancreatic cancers cells. Smad4 silencing up-regulated the expression of
      aldehyde dehydrogenase 1A1 (ALDH1A1) mRNA, whereas forced expression of Smad4 in
      pancreatic cancer cells down-regulated it. Smad4 and ALDH1 expression inversely
      correlated in some human clinical pancreatic adenocarcinoma tissues, suggesting
      that ALDH1 in pancreatic cancer cells was associated with decreased Smad4
      expression. We then examined whether ALDH1 served as a marker of pancreatic
      cancer-initiating cells. Pancreatic cancer cells contained ALDH1(hi) cells in 3%
      to 10% of total cells, with high tumorigenic potential. Because Smad4 is a major
      mediator of transforming growth factor (TGF)-beta family signaling, we
      investigated the regulatory mechanism of ALDH activity by TGF-beta and bone
      morphogenetic proteins. Treatment with TGF-beta attenuated ALDH1(hi) cells in
      several pancreatic cancer cells, whereas bone morphogenetic protein-4 was not as
      potent. Biochemical experiments revealed that TGF-beta regulated ALDH1A1 mRNA
      transcription through binding of Smad4 to its regulatory sequence. It appears
      that TGF-beta negatively regulates ALDH1 expression in pancreatic cancer cells in
      a Smad-dependent manner and in turn impairs the activity of pancreatic cancer
      initiating cells. 

PMID- 25769431
TI  - Placental fractalkine is up-regulated in severe early-onset preeclampsia.
AB  - The pathogenesis of preeclampsia (PE) includes the release of placental factors
      into the maternal circulation, inducing an inflammatory environment in the
      mother. One of the factors may be the proinflammatory chemokine fractalkine,
      which is expressed in the syncytiotrophoblast of human placenta, from where it is
      released into the maternal circulation by constitutive shedding. We examined
      whether placental fractalkine is up-regulated in severe early-onset PE and
      whether the proinflammatory cytokines tumor necrosis factor (TNF)-alpha and IL-6
      are able to increase the expression of fractalkine. Gene expression analysis,
      enzyme-linked immunosorbent assay, and immunohistochemistry consistently showed
      increased fractalkine expression in placentas from severe early-onset PE,
      compared to gestational age-matched controls. Expression of a disintegrin and
      metalloproteinases (ADAMs) 10 and 17, which convert transmembrane fractalkine
      into the soluble form, was significantly increased in these cases. Incubation of
      first-trimester placental explants with TNF-alpha provoked a significant increase
      in fractalkine expression and release of the soluble form, whereas IL-6 had no
      effect. TNF-alpha-mediated up-regulation of placental fractalkine was reversed in
      the presence of the aspirin-derivative salicylate, which impaired activation of
      NF-kappaB p65 in TNF-alpha-treated explants. On the basis of data from placental
      explants, we suggest that increased maternal TNF-alpha may up-regulate the
      expression and release of placental fractalkine, which, in turn, may contribute
      to an exaggerated systemic inflammatory response in PE. 

PMID- 25769432
TI  - Reductive stress impairs myoblasts mitochondrial function and triggers
      mitochondrial hormesis.
AB  - Even though oxidative stress damage from excessive production of ROS is a well
      known phenomenon, the impact of reductive stress remains poorly understood. This
      study tested the hypothesis that cellular reductive stress could lead to
      mitochondrial malfunction, triggering a mitochondrial hormesis (mitohormesis)
      phenomenon able to protect mitochondria from the deleterious effects of statins.
      We performed several in vitro experiments on L6 myoblasts and studied the effects
      of N-acetylcysteine (NAC) at different exposure times. Direct NAC exposure (1mM)
      led to reductive stress, impairing mitochondrial function by decreasing maximal
      mitochondrial respiration and increasing H2O2production. After 24h of incubation,
      the reactive oxygen species (ROS) production was increased. The resulting
      mitochondrial oxidation activated mitochondrial biogenesis pathways at the mRNA
      level. After one week of exposure, mitochondria were well-adapted as shown by the
      decrease of cellular ROS, the increase of mitochondrial content, as well as of
      the antioxidant capacities. Atorvastatin (ATO) exposure (100MUM) for 24h
      increased ROS levels, reduced the percentage of live cells, and increased the
      total percentage of apoptotic cells. NAC exposure during 3days failed to protect
      cells from the deleterious effects of statins. On the other hand, NAC
      pretreatment during one week triggered mitochondrial hormesis and reduced the
      deleterious effect of statins. These results contribute to a better understanding
      of the redox-dependant pathways linked to mitochondria, showing that reductive
      stress could trigger mitochondrial hormesis phenomenon.

PMID- 25769433
TI  - Current treatment of endometrioma.
AB  - IMPORTANCE: Ovarian endometrioma is the most common form of endometriosis.
      Laparoscopy is frequently chosen for its treatment because medical treatment
      alone is inadequate. However, the role of laparoscopic treatment of ovarian
      endometriomas has been challenged by evidence questioning the benefits of
      surgery, especially in cases of young or infertile women. Other therapeutic
      modalities include expectant management, medical therapy, and, in cases of
      infertility, ovulation induction and assisted reproductive technology. None of
      these treatments offer cure of endometriosis. OBJECTIVE: The objective of this
      study was to present data concerning the current management of endometrioma.
      Benefits and complications after treatment and the impact on in vitro
      fertilization outcome are also highlighted. EVIDENCE ACQUISITION: An extensive
      literature search (PubMed) and Cochrane Library review up to December 2013 were
      performed using the following keywords: "endometrioma," "cystectomy,"
      "infertility," "IVF," "malignant transformation," "management," and "recurrence."
      RESULTS: There is a lack of data from randomized trials to inform the optimal
      management of endometriomas with respect to pain relief, recurrence, and
      fertility. CONCLUSIONS AND RELEVANCE: Further studies are needed to determine the
      optimal management of endometrioma. Currently, there is no evidence that surgical
      management improves the fertility of women with endometrioma.

PMID- 25769434
TI  - Ovarian function and reproductive outcomes of female patients with systemic lupus
      erythematosus and the strategies to preserve their fertility.
AB  - Systemic lupus erythematosus (SLE) is a chronic autoimmune systemic disease that
      mainly affects women of reproductive age. Emerging data from recent molecular
      studies show us that estrogen hormone plays a central role in the development of
      this disease. By acting via its cognate receptors ERalpha and ERbeta expressed on
      immune cells, estrogen can modulate immune function in both the innate and
      adaptive immune responses. Interestingly, estrogen may also evoke autoimmune
      responses after binding to B lymphocytes leading to the generation of high
      affinity autoantibodies and proinflammatory cytokines (so-called estrogen-induced
      autoimmunity). Unfortunately, reproductive function of young female patients with
      this disease is commonly compromised by different pathophysiologic processes.
      First, ovarian reserve is diminished even in the presence of mild disease
      suggesting a direct impact of the disease itself on ovarian function possibly due
      to ovarian involvement in the form of autoimmune oophoritis. Second, SLE patients
      with severe manifestations of the disease are treated with alkylating
      chemotherapy agent cyclophosphamide. Cyclophosphamide and other drugs of
      alkylating category have the highest gonadotoxicity. Therefore, SLE patients
      exposed to cyclophosphamide have a much higher risk of developing infertility and
      premature ovarian failure than do the counterparts who are treated with other
      less toxic treatments. Third, the functions of the hypothalamic pituitary ovarian
      axis are perturbed by chronic inflammatory state. And finally adverse pregnancy
      outcomes are more commonly observed in SLE patients such as fetal loss, preterm
      birth, intrauterine fetal growth restriction, preeclampsia-eclampsia, and fetal
      congenital heart block. We aimed in this review article to provide the readers an
      update on how estrogen hormone closely interacts with and induces lupus-prone
      changes in the immune system. We also discuss ovarian function and other
      reproductive outcomes in SLE patients and the current strategies to preserve
      their fertility in the light of the most recent evidence-based findings of the
      clinical trials and molecular studies. 

PMID- 25769435
TI  - Global women's health is more than maternal health: a review of gynecology care
      needs in low-resource settings.
AB  - Women's health care efforts in low-resource settings are often focused primarily
      on prenatal and obstetric care. However, women all over the world experience
      significant morbidity and mortality related to cervical cancer, sexually
      transmitted infections, and urogynecologic conditions as well as gynecologic care
      provision including insufficient and ineffective family planning services. Health
      care providers with an interest in clinical care in low-resource settings should
      be aware of the scope of the burden of gynecologic issues and strategies in place
      to combat the problems. This review article discusses the important concerns both
      in the developing world as well as highlights similar disparities that exist in
      the United States by women's age, race and ethnicity, and socioeconomic status.
      Ultimately, this review article aims to inform and update health care providers
      on critical gynecologic issues in low-resource settings. 

PMID- 25769436
TI  - Natural cocoa consumption: Potential to reduce atherogenic factors?
AB  - Short-term consumption of flavanol-rich cocoa has been demonstrated to improve
      various facets of vascular health. The purpose of the present study was to
      determine the effect of 4 weeks of natural cocoa consumption on selected
      cardiovascular disease (CVD) biomarkers in young (19-35 years) women of differing
      body mass indices (BMI; normal, overweight or obese). Subjects (n = 24) consumed
      a natural cocoa-containing product (12.7 g natural cocoa, 148 kcal/serving) or an
      isocaloric cocoa-free placebo daily for 4 weeks in a random, double-blind manner
      with a 2-week washout period between treatment arms. Fasted (>8-h) blood samples
      were collected before and after each 4-week period. Serum was analyzed to
      determine lipid profile (chemistry analyzer) and CVD biomarkers (26 biomarkers).
      EDTA-treated blood was used to assess monocytes (CD14, CD16, v11b and CD62L),
      while citrate-treated blood was used to measure changes in endothelial
      microparticles (EMPs; CD42a-/45-/144+) by flow cytometry. Natural cocoa
      consumption resulted in a significant decrease in haptoglobin (P = .034), EMP
      concentration (P = .017) and monocyte CD62L (P = .047) in obese compared to
      overweight and normal-weight subjects. Natural cocoa consumption regardless of
      BMI group was associated with an 18% increase in high-density lipoprotein (P =
      .020) and a 60% decrease in EMPs (P = .047). Also, obese subjects experienced a
      21% decrease in haptoglobin (P = .034) and a 24% decrease in monocyte CD62L
      expression in (P = .047) following 4 weeks of natural cocoa consumption.
      Collectively, these findings indicate that acute natural cocoa consumption was
      associated with decreased obesity-related disease risk. More research is needed
      to assess the stability of the observed short-term changes.

PMID- 25769438
TI  - Evaluation of a real-time PCR and a loop-mediated isothermal amplification for
      detection of Xanthomonas arboricola pv. pruni in plant tissue samples.
AB  - Operational capacity of real-time PCR and loop-mediated isothermal amplification
      (LAMP) diagnostic assays for detection of Xanthomonas arboricola pv. pruni was
      established in a ring-test involving four laboratories. Symptomatic and healthy
      almond leaf samples with two methods of sample preparation were analyzed. Kappa
      coefficient, sensitivity, specificity, likelihood ratios and post-test
      probability of detection were estimated to manage the risk associated with the
      use of the two methods. 

PMID- 25769437
TI  - Synaptopathy in the noise-exposed and aging cochlea: Primary neural degeneration
      in acquired sensorineural hearing loss.
AB  - The classic view of sensorineural hearing loss (SNHL) is that the "primary"
      targets are hair cells, and that cochlear-nerve loss is "secondary" to hair cell
      degeneration. Our recent work in mouse and guinea pig has challenged that view.
      In noise-induced hearing loss, exposures causing only reversible threshold shifts
      (and no hair cell loss) nevertheless cause permanent loss of >50% of cochlear
      nerve/hair-cell synapses. Similarly, in age-related hearing loss, degeneration of
      cochlear synapses precedes both hair cell loss and threshold elevation. This
      primary neural degeneration has remained hidden for three reasons: 1) the spiral
      ganglion cells, the cochlear neural elements commonly assessed in studies of
      SNHL, survive for years despite loss of synaptic connection with hair cells, 2)
      the synaptic terminals of cochlear nerve fibers are unmyelinated and difficult to
      see in the light microscope, and 3) the degeneration is selective for cochlear
      nerve fibers with high thresholds. Although not required for threshold detection
      in quiet (e.g. threshold audiometry or auditory brainstem response threshold),
      these high-threshold fibers are critical for hearing in noisy environments. Our
      research suggests that 1) primary neural degeneration is an important contributor
      to the perceptual handicap in SNHL, and 2) in cases where the hair cells survive,
      neurotrophin therapies can elicit neurite outgrowth from spiral ganglion neurons
      and re-establishment of their peripheral synapses. This article is part of a
      Special Issue entitled <Auditory Synaptology>. 

PMID- 25769439
TI  - Probability of pregnancy after sterilization: a comparison of hysteroscopic
      versus laparoscopic sterilization.

PMID- 25769440
TI  - Interest in nonsurgical female permanent contraception among men in Portland,
      Oregon and eastern Maharashtra, India.
AB  - OBJECTIVE: We examined the men's attitudes and perceptions toward the concept of
      female nonsurgical permanent contraception (NSPC) or novel approaches to
      permanent contraception (PC) that do not require incisions or surgical
      equipment/hysteroscope. STUDY DESIGN: Cross-sectional survey of married/partnered
      men in Portland, OR, and rural eastern Maharashtra, India. Descriptive analysis
      was performed. RESULTS: In India (N=150), most men (80%) anticipated that their
      partners would undergo PC in the future, compared to 30% in Portland (N=170).
      About a third (39.6% in India, 82% in Portland) reported being uncomfortable with
      PC for partners due to the need for surgery. Most men (85% in India, 82% in
      Portland) expressed a preference for a hypothetical new method of female NSPC
      over surgery, if safe and effective. CONCLUSION: Most men sampled in two diverse
      settings expressed interest in NSPC for women. IMPLICATIONS: Men's perceptions of
      new female contraceptive methods are important to the contraceptive development
      process. Men may find a safe and effective nonsurgical method of permanent female
      contraception more acceptable than surgical PC.

PMID- 25769441
TI  - Associations of intimate partner violence with unintended pregnancy and pre
      pregnancy contraceptive use in South Asia.
AB  - OBJECTIVE: To assess associations of intimate partner violence (IPV) with
      pregnancy intendedness and pre-pregnancy contraceptive use among pregnant women
      in South Asia. STUDY DESIGN: Cross-sectional analyses were conducted using the
      most recent Demographic and Health Surveys from Bangladesh, India and Nepal for
      married, pregnant women aged 15-49 years who responded to IPV assessments
      specific to current marriage (N=4738). Adjusted logistic and multinomial
      regression analyses were conducted with pooled data to assess associations of IPV
      ever (sexual only, physical only, sexual plus physical or none) with the outcomes
      of pregnancy intendedness (wanted, mistimed or unwanted) and pre-pregnancy
      contraceptive use (no, traditional or modern) for the current pregnancy. RESULTS:
      IPV was not associated with a mistimed or unwanted pregnancy. Sexual IPV was
      associated with pre-pregnancy modern contraceptive use (aOR=2.32, 95% CI=1.24,
      4.36); sexual plus physical IPV was associated with pre-pregnancy traditional
      contraceptive use (aOR=1.85, 95% CI=1.12, 3.07). Post hoc analysis of reasons for
      pre-pregnancy contraceptive discontinuation revealed that women with a history of
      IPV, particularly sexual IPV, had higher prevalence of contraceptive failure
      (sexual only, 37.3%; sexual plus physical, 30.9%; physical only, 22.6%; no IPV,
      13.6%). CONCLUSION: Pregnant women who experienced sexual IPV from husbands were
      more likely to use contraceptives pre-pregnancy but had no reduced risk
      unintended pregnancy, possibly due to higher rates of pre-pregnancy contraceptive
      failure among those with this history. These findings suggest that victims of
      sexual IPV are able to acquire and use family planning services but require more
      support to sustain effective contraceptive use. IMPLICATIONS: Family planning
      services are reaching women affected by sexual IPV, and programs should be
      sensitive to this concern and the heightened vulnerability to contraceptive
      failure these women face. Long-acting reversible contraception could be
      beneficial by allowing women to have greater reproductive control in situations
      of compromised sexual autonomy.

PMID- 25769442
TI  - Missed opportunities for family planning: an analysis of pregnancy risk and
      contraceptive method use among postpartum women in 21 low- and middle-income
      countries.
AB  - OBJECTIVES: To analyze data from recent Demographic and Health Surveys (DHS)
      conducted in 21 low- and middle-income countries (LMICs) to examine patterns of
      interpregnancy intervals, unmet need, pregnancy risk and family planning method
      use and method mix among women 0-23 months postpartum. STUDY DESIGN: Secondary
      analysis of postpartum women aged 15-49 years in 22 DHS surveys from 21 LMICs
      conducted between 2005 and 2012. We applied an adapted unmet need definition for
      postpartum women to look at prospective fertility preferences. We also
      constructed a new composite pregnancy risk indicator for postpartum women who
      have been sexually active since their last birth. RESULTS: In 9 of 22 surveys,
      50% or more of nonfirst births occur at interpregnancy intervals that are too
      short. Overall prospective unmet need for family planning by postpartum women has
      not changed demonstrably since a 2001 analysis and is universally high: 61% of
      all postpartum women across the 21 countries have an unmet need for family
      planning. In 10 of 22 surveys, pregnancy risk rises steadily throughout the 2
      years after birth. In the remaining 12 surveys, the risk of pregnancy peaks at 6
      11 months after birth. Even when postpartum women are using family planning, they
      rely overwhelmingly on short-acting methods (51-96% in 21 of 22 surveys).
      CONCLUSION: Our approach of estimating pregnancy risk by postpartum timing
      confirms a high probability for pregnancies to be less than optimally spaced
      within 2 years of a prior birth and suggests that special consideration is needed
      to effectively reach this population with the right messages and services.
      IMPLICATIONS: Using recent, multicountry data for women within 2 years postpartum
      in LMICs, this paper updates existing estimates of high prospective unmet need
      for family planning and presents a new composite pregnancy risk analysis based on
      postpartum women's actual practices to demonstrate the magnitude of missed
      opportunities for programmatic intervention for the postpartum population.

PMID- 25769443
TI  - First report of malignant catarrhal fever in a captive pudu (Pudu puda).
AB  - A male, six-year-old pudu (Pudu puda) from an Italian zoo was submitted for
      postmortem examination after sudden death. Necroscopy revealed non-suppurative
      bronchopneumonia and degeneration of the liver and haemorrhagic lesions of the
      thymus, pericardium and spleen. Microscopically, multifocal perivascular
      mononuclear cell infiltrates were observed in the kidneys, lungs, spleen, and the
      portal triads of the liver. Histological examination of the brain showed
      meningitis, vasculitis and perivascular cuffs of mononuclear inflammatory cells.
      A region of the DNA polymerase gene of malignant catarrhal fever viruses was
      amplified by real-time PCR and nested PCR. PCR products from the tissue samples
      were sequenced and analysed. The sequences showed 99% similarity with a portion
      of the caprine herpesvirus 2 DNA polymerase gene. This is the first report of
      malignant catarrhal fever in a captive pudu. 

PMID- 25769444
TI  - Fluoroscopic-Guided Radial Endobronchial Ultrasound Without Guide Sheath For
      Peripheral Pulmonary Lesions: A Safe And Efficient Combination.
AB  - BACKGROUND: Several guidelines recommend computed tomography scans for
      populations with high-risk for lung cancer. The number of individuals evaluated
      for peripheral pulmonary lesions (PPL) will probably increase, and with it non
      surgical biopsies. Associating a guidance method with a target confirmation
      technique has been shown to achieve the highest diagnostic yield, but the utility
      of bronchoscopy with radial probe endobronchial ultrasound using fluoroscopy as
      guidance without a guide sheath has not been reported. METHODS: We conducted a
      retrospective analysis of bronchoscopy with radial probe endobronchial ultrasound
      using fluoroscopy procedures for the investigation of PPL performed by
      experienced bronchoscopists with no specific previous training in this particular
      technique. Operator learning curves and radiological predictors were assessed for
      all consecutive patients examined during the first year of application of the
      technique. RESULTS: Fifty-one PPL were investigated. Diagnostic yield and
      visualization yield were 72.5 and 82.3% respectively. The diagnostic yield was
      64.0% for PPL <=20mm, and 80.8% for PPL>20mm. No false-positive results were
      recorded. The learning curve of all diagnostic tools showed a DY of 72.7% for the
      first sub-group of patients, 81.8% for the second, 72.7% for the third, and 81.8%
      for the last. CONCLUSION: Bronchoscopy with radial probe endobronchial ultrasound
      using fluoroscopy as guidance is safe and simple to perform, even without
      specific prior training, and diagnostic yield is high for PPL>and <=20mm. Based
      on these findings, this method could be introduced as a first-line procedure for
      the investigation of PPL, particularly in centers with limited resources.

PMID- 25769445
TI  - Duration of Antibiotic Treatment in Community-Acquired Pneumonia.

PMID- 25769446
TI  - PCA3 and PSA gene activity correlates with the true tumor cell burden in prostate
      cancer lymph node metastases.
AB  - BACKGROUND: Extent of pelvic lymph node (LN) dissemination is a critical
      prognostic feature for patients with prostate cancer (PCa) maintaining extended
      pelvic lymphadenectomy (LAD) as the gold standard for LN-staging. Unfortunately,
      conventional histopathological assessment may miss micrometastasis and recently
      presented immunocytochemical approach of the single cell analysis is still
      intricate. OBJECTIVE: To comparatively assess the potential of Prostate cancer
      gene 3 (PCA3) and prostate specific antigene (PSA) to perform as markers for
      tumor cell load. METHODS: Patients with high risk PCa for LN metastasis
      undergoing either a sentinel LN-guided staging LAD or retropubic radical
      prostatectomy with sentinel-guided pelvic LN dissection were included. LNs were
      investigated by routine histopathology. Tumor cell load was quantified by
      %immunocytochemistry. immunocytochemical single cell analysis. Gene activity was
      determined by qRT-PCR. RESULTS: Twenty four out of 226 LNs were positive in
      routine histopathology and 51 in single cell analysis. PSA mRNA level correlated
      with tumor cell density in patients with a positive immunocytochemistry. Gene
      activity of PCA3 was upregulated in metastatic LNs and correlated with tumor cell
      density in patients with tumor-invaded LNs as detected by immunocytochemistry.
      CONCLUSIONS: PCA3 gene expression discriminates LN metastasis and might
      outperform PSA gene activity in reflecting tumor cell burden in pelvic LNs of PCa
      patients.

PMID- 25769447
TI  - A case study on the identification of confounding factors for gene disease
      association analysis.
AB  - Variation in the expression of genes arises from a variety of sources. It is
      important to remove sources of variation between arrays of non-biological origin.
      Non-biological variation, caused by lurking confounding factors, usually attracts
      little attention, although it may substantially influence the expression profile
      of genes. In this study, we proposed a method which is able to identify the
      potential confounding factors and highlight the non-biological variations. We
      also developed methods and statistical tests to study the confounding factors and
      their influence on the homogeneity of microarray data, gene selection, and
      disease classification. We explored an ovarian cancer gene expression profile and
      showed that data batches and arraying conditions are two confounding factors.
      Their influence on the homogeneity of data, gene selection, and disease
      classification are statistically analyzed. Experiments showed that after
      normalization, their influences were removed. Comparative studies further showed
      that the data became more homogeneous and the classification quality was
      improved. This research demonstrated that identifying and reducing the impact of
      confounding factors is paramount in making sense of gene-disease association
      analysis. 

PMID- 25769448
TI  - MicroRNAs as new biomarkers for human papilloma virus related head and neck
      cancers.
AB  - Head and neck cancers are the sixth most common cancer in the world and the
      predominant type of which consist of squamous cell carcinomas (head and neck
      squamous cell carcinoma, HNSCC). Besides tobacco smoking and alcohol consumption,
      human papilloma virus (HPV) infection is the third leading cause of the
      occurrence of HNSCC. The presence of HPV is a distinct group of head and neck
      cancers exhibiting epidemiological, histopathological, clinical and prognostic
      differences opposed to the typical HNSCC. HPV positive HNSCC normally have a
      favorable prognosis compared with HPV negative HNSCC, so biomarkers suitable for
      the early detection of HPV positive HNSCC should be developed urgently to improve
      patient outcomes. HPV DNA screening is sensitive, but probably not useful because
      of the high prevalence of oral HPV and low risk of HNSCC. MicroRNAs (miRNAs)
      constitute a class of small non-coding RNAs that act as post-transcriptional
      regulators of gene expression. Since miRNAs have a role in the cancer development
      and HPV status may affect the miRNAs expression pattern in HNSCC, the specific of
      miRNAs' expression in HPV positive HNSCC may expound the role of HPV in HNSCC and
      be new biomarkers for the early detection of HNSCC. More excitingly, saliva as
      proximal biofluid in the context of HNSCC contains a good deal of miRNAs. These
      miRNAs are stabile and may be suitable for noninvasive biomarkers of HNSCC. 

PMID- 25769449
TI  - DNMT3b -149C/T promoter variants and methylation of colorectal cancer-associated
      genes.
AB  - OBJECTIVE: DNMT3B overexpression has been linked with the CpG island methylator
      phenotype in various cancers. Considering the role of the DNMT3b -149C/T promoter
      polymorphism on the gene expression, we evaluated the associations of this
      polymorphism with colorectal cancer (CRC) risk and hypermethylation of six tumor
      suppressor genes in CRC tumors. METHODS: The DNMT3b was genotyped by PCR-RFLP in
      108 sporadic CRC patients and 185 healthy controls and methylation of genes'
      promoter was determined by methylation specific PCR. RESULTS: In comparison to
      controls, the TT genotype was strongly associated with a high risk of cancer
      incidence (OR = 3.3, 95% CI = 1.6-6.9). The frequency of methylated hMLH1 was
      significantly higher in patients with the DNMT3bCT genotype (p= 0.03), especially
      in male subjects. The frequency of hMLH1 methylation was significantly higher in
      young patients (< 60 years) with the CT/TT genotypes. The combined CT/TT
      genotypes also showed significant associations with the ECAD methylation in the
      entire group of patients (p= 0.04), in patients with distal tumors, and in old
      cases. The DNMT3b genotype was not associated with methylation of other genes
      examined in this study. CONCLUSIONS: Our results suggest that DNMT3b polymorphism
      is involved in the development of colon cancer and non-random genes promoter
      methylation among Iranian population.

PMID- 25769450
TI  - LncRNA expression profile reveals the potential role of lncRNAs in gastric
      carcinogenesis.
AB  - Gastric cancer ranks the second highest death rate and is the highest morbidity
      digestive system malignancy in China. Few reports have elucidated the role of
      long non-coding RNAs (lncRNAs) in the gastric cancer pathogenesis. The present
      study was aimed to identify aberrantly expressed lncRNAs involved in the
      progression of gastric cancer and explored their potential functions. A total of
      1,297 lncRNAs and 2,037 mRNAs that showed significantly differential expression
      level between gastric tumor samples and matched adjacent normal tissues were
      identified in six pairs of samples using microarray assay. To further explore
      their functions, lncRNAs were classified into different subgroups and mRNAs were
      clustered into several pathways. The expression level of 4 lncRNAs: UCA1, lincRNA
      BBOX1-2, CR594506 and BC015134 were further confirmed in another cohort of 10
      gastric patients by real-time PCR assay. A coding-non-coding co-expression
      network revealed that the four validated lncRNAs were correlated with twenty-six
      mRNAs which gave clues about the potential roles of these lncRNAs in the process
      of gastric cancer progression. 

PMID- 25769451
TI  - Evaluating the clinical feasibility: The direct bisulfite genomic sequencing for
      examination of methylated status of E3 ubiquitin ligase RNF180 DNA promoter to
      predict the survival of gastric cancer.
AB  - BACKGROUND: E3 ubiquitin ligase Ring finger protein 180 (RNF180) has been
      identified as a novel tumor suppressor in gastric cancer and the methylated CpG
      site count of RNF180 DNA promoter can predict the prognosis for gastric cancer
      patients. OBJECTIVE: In the previous study, we demonstrated that methylated CpG
      site count of RNF180 DNA promoter was significantly associated with the survival
      of patients with gastric cancer using the bisulfite genomic sequencing (BGS) in
      the gastric cancer tissue with five clones per sample. It was so complicate for
      each patient underwent the BGS detection with clones. It is important to explore
      a simple, rapid and accurate method to detect methylated CpG site count to
      predicting the prognosis for gastric cancer patients. METHODS: At present study,
      we detected hypermethylated and hypomethylated CpG site count of RNF180 DNA
      promoter in samples of 480 gastric cancer patients by direct bisulfite
      sequencing. RESULTS: We found that patients who possessed seven or less
      hypermethylated CpG sites of RNF180 DNA promoter had much better survival (p=
      0.008), which was similar to our previous research results by using the BGS with
      clones. With the multivariate survival analysis, we found that T stage, N stage
      and hypermethylated CpG site count of RNF180 DNA promoter were the independent
      predictors of prognosis for gastric cancer patients. CONCLUSIONS: hypermethylated
      CpG site count of RNF180 DNA promoter for evaluating the prognosis of gastric
      cancer was reasonable by using the direct bisulfite sequencing.

PMID- 25769452
TI  - Quantification of autoantibodies to plasminogen in plasma of patients with
      cancer.
AB  - BACKGROUND: The investigation of autoantibodies which may play a role in the
      processes of angiogenesis and tumorogenesis is important in the early diagnostis
      of cancer. OBJECTIVE: This study aimed to investigate the levels of
      autoantibodies to Glu-plasminogen (Pg) in plasma of patients with tumors.
      METHODS: Plasma samples from healthy volunteers were compared with samples from
      patients with prostate cancer using 2D electrophoresis and MALDI-TOF mass
      spectrometry. Plasma samples from 25 patients with prostate cancer, 15 patients
      with benign prostatic hyperplasia (BPH), 29 patients with breast cancer, and 43
      healthy volunteers were tested using ELISA to anti-Pg IgG autoantibodies.
      Affinity chromatography on Pg-sepharoses was used to assess the quantity of anti
      Pg IgG in control plasma and plasma of prostate cancer patients. ATTESTAT program
      was used for nonparametric analysis. RESULTS: Using 2D electrophoresis, marker
      spots below 50 kD were detected in prostate cancer samples. These spots were
      identified as fragments of Pg and IgG. Using affinity chromatography on Pg
      sepharose, the quantity of IgG bound to Pg versus total IgG was determined to be
      9% in control and 27% in prostate cancer samples. The frequency of occurence of
      elevated levels of anti-Pg IgG was 84% in prostate cancer samples, 69% in breast
      cancer samples, 40% in BPH samples, and 11% in healthy plasma. CONCLUSIONS:
      Autoantibodies to Pg may be involved in tumorogenesis and elevated levels of anti
      Pg IgG antibodies may be a risk factor for tumor development.

PMID- 25769453
TI  - Changed expression and function of P-gp in peripheral blood CD56 + cells
      predicting chemoresistance in non-Hodgkin lymphoma patients.
AB  - BACKGROUND: Multi-drug resistance (MDR) remains to be a major obstacle toward
      successful chemotherapy of NHL patients. P-glycoprotein (P-gp), a classical
      protein associated with MDR, has been observed in peripheral blood CD56 + cells
      with high expression and activity. While the CD56 expression has been shown to be
      associated with a highly aggressive clinical course and chemoresistance in Non
      Hodgkin lymphoma (NHL). OBJECTIVE: To investigate the role of peripheral blood
      CD56+ cells in predicting the MDR of NHL by determining the P-gp expression and
      function of the CD56+ cells. METHODS: The expression levels of MDR1 mRNA and MRP1
      mRNA and the function of P-gp in the CD56+ cells were evaluated by RT-qPCR and
      flow cytometry respectively in 52 chemoresistant and 47 chemosensitive NHL
      patients and 48 healthy donors. RESULTS: In the chemoresistant group, the mRNA
      expression level of MDR1 elevated about 2~8 fold (mean = 4.24 +/- 0.17) in the
      purified CD56+ cells, whereas there was only about 1~2.5 fold (mean = 1.69 +/-
      0.41) elevated for the MRP1 gene. The mean fold change of MDR1 mRNA expression in
      the chemoresistant group significantly increased when compared with that in the
      chemosensitive patients (P < 0.001). The mean fluorescence intensities (MFI) in
      the total gated CD56+ and Rho123 double positive cells in the chemoresistant
      patients statistically decreased compared with that in the healthy controls and
      the chemosensitive NHL patients (P < 0.01). CONCLUSIONS: Determining the P-gp
      expression and function of the peripheral blood CD56+ cells may help predict the
      MDR of NHL, thus has profound guiding significance for NHL treatment.

PMID- 25769454
TI  - Emerging role of microRNA-21 in colorectal cancer.
AB  - Colorectal cancer (CRC) is one of the most common types of cancers worldwide. In
      spite of much progress in surgery, chemotherapy and molecular targeted therapy,
      the mortality rate has only decreased slightly over the past years. MicroRNAs are
      18-25 nucleotide, noncoding RNA molecules that regulate the translation of many
      genes. Evidence suggests that miRNAs may play an important role in a variety of
      cellular biological processes, such as cell growth, differentiation, metabolism,
      invasion, angiogenesis. Recently, miR-21 is found to be aberrantly expressed in
      CRC and miR-21 has been recognized to perform significantly in CRC, where miR-21
      can regulate several different target genes and pathways involving tumor
      proliferation, invasion and metastasis. In this study, we will focus on the
      critical role of miR-21 in CRC. Hopefully, the information obtained may lead to a
      better understanding of the pathogenesis and development of novel therapeutic
      strategies for this disease. 

PMID- 25769455
TI  - Expression of BNIP3 and its correlations to hypoxia-induced autophagy and
      clinicopathological features in salivary adenoid cystic carcinoma.
AB  - BACKGROUND: The expression of Bcl-2/adenovirus E1B 19 kDa-interacting protein3
      (BNIP3) has been explored in many human malignancies, but not in adenoid cystic
      carcinoma (ACC). OBJECTIVE: This study investigated the clinical significance of
      expression of BNIP3 in ACC tissues and cells and elucidated its correlations to
      hypoxia-induced autophagy. METHODS: Immunohistochemical and immunofluorescence
      staining were used to explore BNIP3, HIF-1alpha and LC3 expression. RESULTS:
      BNIP3 was positively expressed in 41 cases (63.1%), and was significantly
      correlated with histological grade (P= 0.001). HIF-1alpha was positively
      expressed in 52 cases (80.0%) and was significantly correlated with TNM stage (P=
      0.023) and histological grade (P= 0.024). LC3 was positively expressed in 37
      cases (56.9%) and was significantly correlated with TNM stage (P= 0.019). The
      expression of BNIP3 was correlated with HIF-1alpha expression (P= 0.011). The
      overall survival in the negative BNIP3 expression group tended to be better than
      in the positive BNIP3 expression (P= 0.011). In vitro experiment, BNIP3
      immunofluorescence staining was detected in cells treated with CoCl2 (for hypoxic
      condition). CONCLUSIONS: The data indicated that BNIP3 plays a vital role in the
      tumorigenesis of adenoid cystic carcinoma and could be a new target for gene
      therapy of adenoid cystic carcinoma.

PMID- 25769456
TI  - Quantification of concentration and assessment of EGFR mutation in circulating
      DNA.
AB  - BACKGROUND: Analysis of circulating cell-free DNA in blood is considered as a
      liquid biopsy, which enables non-invasive and repetitive investigation of the
      tumor DNA. The potential clinical usefulness of circulating DNA is frequently
      examined in lung cancer. Thus, our aim was assessment if chemotherapy influences
      the circulating DNA concentration. PATIENTS AND METHODS: Fifty-seven lung cancer
      patients in advanced stages of the disease were examined. Quantification of
      circulating DNA was determined by TERT amplification. RESULTS: Distant metastases
      and chemotherapy were significantly connected with circulating DNA level.
      Patients treated with conventional chemotherapy had statistically lower
      circulating DNA levels when compared to patients not treated with chemotherapy.
      Histological types of tumor and smoking status were not associated with
      circulating DNA concentration. In this study, we have also genotyped the EGFR
      mutations in exon 19 of circulating DNA using the TaqMan PCR assays. One patient
      carried a deletion (2235-49del in EGFR), which has been confirmed by sequencing.
      CONCLUSIONS: Circulating DNA is easy to obtain, convenient biological material,
      although quantitative analysis cannot be used as diagnostic tool, but it can be
      applied to determination of EGFR mutations, basis of the tyrosine kinase
      inhibitors application.

PMID- 25769457
TI  - Non-POU Domain-Containing Octamer-Binding Protein Negatively Regulates HIV-1
      Infection in CD4(+) T Cells.
AB  - HIV-1 interacts with numerous cellular proteins during viral replication.
      Identifying such host proteins and characterizing their roles in HIV-1 infection
      can deepen our understanding of the dynamic interplay between host and pathogen.
      We previously identified non-POU domain-containing octamer-binding protein (NonO
      or p54nrb) as one of host factors associated with catalytically active
      preintegration complexes (PIC) of HIV-1 in infected CD4(+) T cells. NonO is
      involved in nuclear processes including transcriptional regulation and RNA
      splicing. Although NonO has been identified as an HIV-1 interactant in several
      recent studies, its role in HIV-1 replication has not been characterized. We
      investigated the effect of NonO on the HIV-1 life cycle in CD4(+) T cell lines
      and primary CD4(+) T cells using single-cycle and replication-competent HIV-1
      infection assays. We observed that short hairpin RNA (shRNA)-mediated stable NonO
      knockdown in a CD4(+) Jurkat T cell line and primary CD4(+) T cells did not
      affect cell viability or proliferation, but enhanced HIV-1 infection. The
      enhancement of HIV-1 infection in Jurkat T cells correlated with increased viral
      reverse transcription and gene expression. Knockdown of NonO expression in Jurkat
      T cells modestly enhanced HIV-1 gag mRNA expression and Gag protein synthesis,
      suggesting that viral gene expression and RNA regulation are the predominantly
      affected events causing enhanced HIV-1 replication in NonO knockdown (KD) cells.
      Furthermore, overexpression of NonO in Jurkat T cells reduced HIV-1 single-cycle
      infection by 41% compared to control cells. Our data suggest that NonO negatively
      regulates HIV-1 infection in CD4(+) T cells, albeit it has modest effects on
      early and late stages of the viral life cycle, highlighting the importance of
      host proteins associated with HIV-1 PIC in regulating viral replication. 

PMID- 25769458
TI  - Effects of female increased body mass index on in vitro fertilization cycles
      outcome.
AB  - BACKGROUND: As being overweight can impair female spontaneous fertility or after
      assisted reproductive technology (ART) cycles, the aim of this study was to
      compare in vitro fertilization (IVF) outcome according to women's body mass index
      (BMI). METHODS: Retrospective study conducted from 2006 to 2009 in the IVF unit
      of Nantes University Hospital, France. 582 patients undergoing standard
      infertility workup and controlled ovarian stimulation were categorized according
      to BMI into two groups: group 1: normal weight (20-24.9 kg/m(2); n=409) and group
      2: overweight and obese (>=25 kg/m(2); n=149). Basal hormonal status, smoking
      habitus, infertility duration, IVF cycle parameters and outcome were recorded.
      RESULTS: Basal LH, FSH and estradiol levels were higher in group 1 than group 2,
      but ovarian reserve markers were comparable across the two BMI groups. Higher
      doses of gonadotropins were required in group 2 to obtain equivalent ovarian
      response than in group 1. No difference was observed on ovarian response and
      embryonic parameters. Cycle outcome were not significantly different between both
      groups, but we found a strong trend towards increasing transfer cancellation and
      miscarriage rates in group 2. CONCLUSION: Although overweight and obesity do not
      compromise ovarian stimulation results whenever adaptation of recombinant FSH
      doses is made, our data suggest an increased risk of cancellation transfer and
      miscarriage rate, leading to poorer IVF outcome.

PMID- 25769459
TI  - Orai1-Orai2 complex is involved in store-operated calcium entry in chondrocyte
      cell lines.
AB  - Ca(2+) influx via store-operated Ca(2+) entry (SOCE) plays critical roles in many
      essential cellular functions. The Ca(2+) release-activated Ca(2+) (CRAC) channel
      complex, consisting of Orai and STIM, is one of the major components of store
      operated Ca(2+) (SOC) channels. Our previous study demonstrated that histamine
      can cause sustained Ca(2+) entry through SOC channels in OUMS-27 cells derived
      from human chondrosarcoma. This SOCE was increased by low- and decreased by high
      concentrations of 2-aminoethoxydiphenyl borate. Quantitative reverse
      transcription PCR and Western blot analyses revealed abundant expressions of
      Orai1, Orai2 and STIM1. Introduction of dominant negative mutant of Orai1, or
      siOrai1 knockdown significantly attenuated SOCE. Following histamine application,
      single molecule imaging using total internal reflection fluorescence (TIRF)
      microscopy demonstrated punctate Orai1-STIM1 complex formation in plasma
      membrane. In contrast, knockdown or over-expression of Orai2 resulted in an
      increase or a decrease in SOCE, respectively. Finally, TIRF imaging revealed
      direct coupling between Orai1 and Orai2, and suggested that Orai2 reduces Orai1
      function by formation of a hetero-tetramer. These results provide substantial
      evidence that Orai1, Orai2 and STIM1 form functional CRAC channels in OUMS-27
      cells and that these complexes are responsible for sustained Ca(2+) entry in
      response to agonist stimulation.

PMID- 25769460
TI  - Emergency department and inpatient hospital use by Medicare beneficiaries in
      patient-centered medical homes.
AB  - STUDY OBJECTIVE: Patient-centered medical homes are primary care practices that
      focus on coordinating acute and preventive care. Such practices can obtain
      patient-centered medical home recognition from the National Committee for Quality
      Assurance. We compare growth rates for emergency department (ED) use and costs of
      ED visits and hospitalizations (all-cause and ambulatory-care-sensitive
      conditions) between patient-centered medical homes recognized in 2009 or 2010 and
      practices without recognition. METHODS: We studied a sample of US primary care
      practices and federally qualified health centers: 308 with and 1,906 without
      patient-centered medical home recognition, using fiscal year 2008 to 2010
      Medicare fee-for-service data. We assessed average annual practice-level payments
      per beneficiary for ED visits and hospitalizations and rates of ED visits and
      hospitalizations (overall and ambulatory-care-sensitive condition) per 100
      beneficiaries before and after patient-centered medical home recognition, using a
      difference-in-differences regression model comparing patient-centered medical
      homes and propensity-matched non-patient-centered medical homes. RESULTS:
      Comparing patient-centered medical home with non-patient-centered medical home
      practices, the rate of growth in ED payments per beneficiary was $54 less for
      2009 patient-centered medical homes and $48 less for 2010 patient-centered
      medical homes relative to non-patient-centered medical home practices. The rate
      of growth in all-cause and ambulatory-care-sensitive condition ED visits per 100
      beneficiaries was 13 and 8 visits fewer for 2009 patient-centered medical homes
      and 12 and 7 visits fewer for 2010 patient-centered medical homes, respectively.
      There was no hospitalization effect. CONCLUSION: From 2008 to 2010, outpatient ED
      visits increased more slowly for Medicare patients being treated by patient
      centered medical home practices than comparison non-patient-centered medical
      homes. The reduction was in visits for both ambulatory-care-sensitive and non
      ambulatory-care-sensitive conditions, suggesting that steps taken by practices to
      attain patient-centered medical home recognition such as improving care access
      may decrease some of the demand for outpatient ED care.

PMID- 25769461
TI  - Changes in Emergency Department Use Among Young Adults After the Patient
      Protection and Affordable Care Act's Dependent Coverage Provision.
AB  - STUDY OBJECTIVE: Since September 2010, the Patient Protection and Affordable Care
      Act has allowed young adults to remain as dependents on their parents' private
      health plans until age 26 years. This insurance expansion could improve the
      efficiency of medical care delivery by reducing unnecessary emergency department
      (ED) use. We evaluated the effect of this provision on ED use among young adults.
      METHODS: We used a nationally representative ED visit database of more than 17
      million visits from 2007 to 2011. Our analysis compared young adults aged 19 to
      25 years (the age group targeted by the law) with slightly older adults aged 27
      to 29 years (control group), before and after the implementation of the law.
      RESULTS: The quarterly ED-visit rate decreased by 1.6 per 1,000 population (95%
      confidence interval 1.2 to 2.1) among targeted young adults after the
      implementation of the provision, relative to a comparison group. The decrease was
      concentrated among women, weekday visits, nonurgent conditions, and conditions
      that can be treated in other settings. We found no effect among weekend visits or
      visits due to injuries or urgent conditions. The provision also changed the
      health insurance composition of ED visits; the fraction of privately insured
      young adults increased, whereas the fraction of those insured through Medicaid
      and those uninsured decreased. CONCLUSION: The Patient Protection and Affordable
      Care Act dependent coverage expansion was associated with a statistically
      significant yet modest decrease in ED use, concentrated in the types of ED visits
      that were likely to be responsive to changes to insurance status. In response to
      the law, young adults appeared to have altered their visit pattern to reflect a
      more efficient use of medical care.

PMID- 25769462
TI  - Bronchovascular reconstructions for lung cancer: improvements over time.

PMID- 25769463
TI  - Current status and recommendations for use of the frozen elephant trunk
      technique: a position paper by the Vascular Domain of EACTS.
AB  - The implementation of new surgical techniques offers chances but carries risks.
      Usually, several years pass before a critical appraisal and a balanced opinion of
      a new treatment method are available and rely on the evidence from the literature
      and expert's opinion. The frozen elephant trunk (FET) technique has been
      increasingly used to treat complex pathologies of the aortic arch and the
      descending aorta, but there still is an ongoing discussion within the surgical
      community about the optimal indications. This paper represents a common effort of
      the Vascular Domain of EACTS together with several surgeons with particular
      expertise in aortic surgery, and summarizes the current knowledge and the state
      of the art about the FET technique. The majority of the information about the FET
      technique has been extracted from 97 focused publications already available in
      the PubMed database (cohort studies, case reports, reviews, small series, meta
      analyses and best evidence topics) published in English. 

PMID- 25769465
TI  - MitraClip therapy and surgical edge-to-edge repair in patients with severe left
      ventricular dysfunction and secondary mitral regurgitation: is the solution here?

PMID- 25769464
TI  - The TRIBECA study: (TRI)fecta (B)ioprosthesis (E)valuation versus (C)arpentier
      Magna-Ease in (A)ortic position.
AB  - OBJECTIVE: To determine whether the Trifecta bioprosthetic aortic valve produces
      postoperative haemodynamic results comparable with or better than those of the
      Magna Ease aortic valve bioprosthesis. METHODS: We retrospectively reviewed the
      medical records of patients who had undergone aortic valve replacement with
      Trifecta or Magna Ease prostheses at eight European institutions between January
      2011 and May 2013, and analysed early postoperative haemodynamic performance by
      means of echocardiography. RESULTS: A total of 791 patients underwent aortic
      valve replacement (469 Magna Ease, 322 Trifecta). Haemodynamic variables were
      evaluated on discharge and during the follow-up (minimum 6 months, maximum 12
      months). The mean gradient and the indexed effective orifice area (IEOA) were as
      follows: 10 mmHg [interquartile range (IQR): 8-13] and 1.10 cm(2)/m(2) (IQR: 0.95
      1.27) for Trifecta; 16 mmHg (IQR: 11-22) and 0.96 cm(2)/m(2) (IQR: 0.77-1.13) for
      Magna Ease (P < 0.001). These significant differences were maintained across all
      valve sizes. Similar statistically significant differences were found when
      patients were matched and/or stratified for preoperative characteristics: body
      surface area, ejection fraction, mean gradients and valve size. Severe prosthesis
      patient mismatch (IEOA: <0.65 cm(2)/m(2)) was detected in 2 patients (0.6%) with
      Trifecta and 40 patients (8.5%) with Magna Ease (P < 0.001). CONCLUSIONS: The
      haemodynamic performance of the Trifecta bioprosthesis was superior to that of
      the Magna Ease valve across all conventional prosthesis sizes, with almost no
      incidence of severe patient-prosthesis mismatch. The long-term follow-up is
      needed to determine whether these significant haemodynamic differences will
      persist, and influence clinical outcomes.

PMID- 25769466
TI  - Efficacy of the 'intrapulmonary-artery septation' surgical approach for Fontan
      candidates with unilateral pulmonary arterial hypoplasia?.
AB  - OBJECTIVES: The bilaterally unbalanced development of pulmonary arteries (PAs),
      as a result of unilateral pulmonary arterial hypoplasia (PAhypo) makes patients
      either ineligible for the Fontan operation or candidates for the one-lung Fontan
      operation. In the present study, we examined the efficacy of intrapulmonary
      artery septation (IPAS), a technique we reported in 2007 in which a septation is
      constructed within the central PA, in patients with unilateral PAhypo. METHODS:
      Sixteen patients with unilateral PAhypo and an affected PA index of <=60
      mm(2)/m(2), including non-confluent PA (NCPA), underwent IPAS between January
      2000 and March 2012; patients with pulmonary venous obstruction were excluded
      from this study. We compared the affected PA index values before and after IPAS
      and after the Fontan operation as well as the bilateral pulmonary blood flow
      ratio using pulmonary scintigraphy. The post-Fontan operation values of central
      venous pressure (CVP), pulmonary vascular resistance (PVR), ventricular end
      diastolic pressure (VEDP), cardiac index (CI) and arterial oxygen saturation
      (SaO2) at the most recent cardiac catheterization, as well as the pre-IPAS and
      post-Fontan New York Heart Association (NYHA) classification levels were
      examined. RESULTS: One patient died after IPAS (survival rate, 93.8%). Thirteen
      (86.7%) of the surviving 15 patients underwent the Fontan operation. The mean PA
      indexes were 25.5 +/- 18.9 mm(2)/m(2) before IPAS and 67.9 +/- 34.2 mm(2)/m(2)
      after IPAS (P = 0.003); the mean PA index was 71.1 +/- 50.0 mm(2)/m(2) after the
      Fontan operation. Restenosis did not occur after the Fontan operation, and the PA
      diameters were maintained. The mean affected/unaffected lung blood flow ratio was
      0.89 +/- 0.67. The most recent cardiac catheterization after the Fontan operation
      indicated the following values: CVP, 11.7 +/- 1.8 mmHg; PVR, 1.3 +/- 0.4 U m(2);
      EDP, 5.7 +/- 2.0 mmHg; CI, 3.1 +/- 0.5 l/min/m(2) and SaO2, 94.9 +/- 2.0%. The
      mean pre-IPAS and post-Fontan NYHA levels were 2.3 +/- 0.6 and 1.2 +/- 0.4,
      respectively (P = 0.0002). CONCLUSIONS: With IPAS, the affected PA diameters
      increased significantly, and were maintained after the Fontan operation, and
      continuity of the native PAs was achieved. IPAS is very effective for patients
      suffering from otherwise intractable diseases.

PMID- 25769467
TI  - Thoracoabdominal repair evolving.

PMID- 25769468
TI  - Re-expansion pulmonary oedema after minimally invasive cardiac surgery with right
      mini-thoracotomy.
AB  - OBJECTIVES: Re-expansion pulmonary oedema (RPO) sometimes occurs after minimally
      invasive cardiac surgery (MICS) with single-lung ventilation. However, it has not
      been widely recognized as a serious complication. The aim of this study is to
      evaluate the occurrence rate and risk factors of RPO. METHODS: A total of 381
      consecutive patients who underwent MICS with right mini-thoracotomy from March
      2005 to October 2013 were retrospectively reviewed. RESULTS: RPO was observed in
      8 (2.1%) patients. In the preoperative data, greater percentages of preoperative
      use of steroid or immunosuppressant were found in patients with RPO (25% [2/8] vs
      1% [4/373]; P = 0.0056). In the operative data, significantly longer operation,
      cardiopulmonary bypass (CPB) and aortic cross-clamping (ACC) times as well as
      greater percentages of second CPB run were found in patients with RPO (388 +/- 80
      vs 272 +/- 61 min; P < 0.0002, 253 +/- 79 vs 158 +/- 50 min; P = 0.0009, 162 +/-
      65 vs 108 +/- 38 min; P = 0.020 and 38% [3/8] vs 1.3% [5/373]; P < 0.0003). The
      overall 30-day mortality rate was 0.8% (3/381) and the 30-day mortality rate of
      patients with RPO was 12.5% (1/8). Significantly prolonged initial ventilation
      time, intensive care unit and postoperative hospital stay were observed in
      patients with RPO (P = 0.0022, <0.0001 and 0.0003, respectively). Multivariate
      logistic analysis detected preoperative use of steroid or immunosuppressant and
      prolonged ACC time (>=156 min) as independent risk factors for RPO after MICS
      (odds ratio [OR]: 87.6 [95% confidence interval, CI: 4.1-2463.8]; P = 0.006 and
      OR: 36.0 [95% CI: 4.8-731.4]; P < 0.001). CONCLUSIONS: RPO should be recognized
      as one of the most serious complications after MICS with right mini-thoracotomy.
      More accurate risk factors of prolonged lung malperfusion and steroid use on RPO
      after MICS should be investigated.

PMID- 25769469
TI  - Results of extracardiac conduit total cavopulmonary connection in 500 patients.
AB  - OBJECTIVES: This single-institution study aimed to evaluate the early to mid-term
      outcomes of extracardiac conduit total cavopulmonary connection (EC-TCPC).
      METHODS: Between March 1994 and March 2014, 500 patients (median age, 3.4 years)
      underwent EC-TCPC at our hospital. One hundred and twenty-three patients (24.6%)
      showed heterotaxy, and fenestration was created in 6 patients (1.2%). The
      standard institutional treatment policy included postoperative anticoagulation
      and individualized cardiovascular medication. The mortality and morbidity rates,
      haemodynamic status, cardiopulmonary exercise capacity and liver examination
      results during the follow-up period (median, 6.7 years) were retrospectively
      reviewed. RESULTS: There were 2 early and 17 late deaths. The Kaplan-Meier
      estimated survival rate was 96.2% at 10 years and 92.8% at 15 years.
      Bradyarrhythmia and tachyarrhythmia occurred in 19 and 13 patients, respectively.
      Other late-occurring morbidities included protein-losing enteropathy in 8,
      thromboembolism in 5, bleeding complications in 6 and liver cirrhosis in 1
      patient. The rate of freedom from late-occurring morbidities was 82.1% at 15
      years. In the multivariate analysis, heterotaxy was found to be a predictor for
      mortality (P = 0.02), whereas age at operation was a predictor for new-onset
      arrhythmias (P = 0.048). In the cardiopulmonary exercise test (n = 312), the peak
      VO2 was 84.9 +/- 17.3% of the predicted value, which tended to decrease with age
      (R(2) = 0.32) and elapsed time since operation (R(2) = 0.21). Postoperative
      cardiac catheterization (n = 468; time from surgery, 3.6 +/- 4.3 years) showed
      central venous pressure of 9.9 +/- 2.4 mmHg, ventricular end-diastolic pressure
      of 5.2 +/- 3.3 mmHg, cardiac index of 3.4 +/- 0.8 l/min/m(2) and arterial oxygen
      saturation of 94.2 +/- 4.8%. In 101 patients who were followed up for >=10 years,
      amino-terminal type III procollagen peptide and collagen type IV levels exceeded
      the normal ranges in 52.9 and 75.2% of patients, respectively, and liver
      ultrasonography revealed hyper-echoic spots in 43.3% of patients. CONCLUSIONS:
      The early to mid-term outcomes of post-EC-TCPC patients managed with
      individualized pharmacotherapy were excellent, with low mortality and morbidity
      rates; however, development of late-occurring morbidities specific to Fontan
      physiology, including exercise intolerance and liver disease, must be carefully
      monitored during the long-term follow-up.

PMID- 25769470
TI  - Seroepidemiological and entomological survey in a new focus of zoonotic visceral
      leishmaniasis in Kars province, Northeastern Turkey.
AB  - Visceral leishmaniasis (VL) has now been recorded from 38 provinces of Turkey.
      Twenty-one VL cases were reported within six years from settlements located in
      most northeastern Turkey and we therefore aimed to carry out an entomological and
      seroepidemiological survey in this new focus for clarifying risk factors. Blood
      samples from 290 children and 165 dogs were collected. Sera samples were
      investigated for anti-Leishmania antibodies using indirect fluorescent antibody
      test. Sand fly collection for determining the fauna and seasonal activity was
      performed in all settlements by CDC light traps between June and September 2006.
      Although no seropositive child was detected during the survey the overall
      seroprevalence rate of canine leishmaniasis was found as 7.2%. A total of 4154
      sand flies were collected and 10 species of genus Phlebotomus were identified
      belonging to Adlerius, Larroussius, Paraphlebotomus and Phlebotomus subgenera.
      Among them Phlebotomus kandelakii s.l. (55.44%), Phlebotomus balcanicus (12.62%)
      and Phlebotomus neglectus (4.40%) was detected as probable vector species for
      this new focus. The poor sanitation, very high population size of sand flies,
      probably because of very short season, no control measures for sand flies as well
      as dogs, and presence of microclimate suitable for sand flies were considered as
      main risk factors in the area. 

PMID- 25769471
TI  - Canine and human Dirofilaria infections in the Balkan Peninsula.
AB  - Dirofilaria immitis and Dirofilaria repens infections are mosquito-borne
      diseases, mainly of dogs. Both parasites are zoonotic, and they sometimes cause
      serious infections in humans. The aim of this short review was to examine the
      situation in the Balkan Peninsula, from where it is not always easy to obtain
      suitable data, often reported in journals and other publications difficult to be
      retrieved and with poor or no visibility. The review included data from
      international and regional literature, doctoral theses, and conference
      proceedings. 

PMID- 25769472
TI  - Doxycycline levels and anti-Wolbachia antibodies in sera from dogs experimentally
      infected with Dirofilaria immitis and treated with a combination of
      ivermectin/doxycycline.
AB  - Sera from Dirofilaria immitis-experimentally infected dogs treated with a
      combination of ivermectin/doxycycline were analysed for doxycycline levels by
      HPLC and anti-Wolbachia Surface Protein (rWSP) antibodies by ELISA and compared
      with sera from dogs treated with doxycycline alone. Results show that doxycycline
      levels were not statistically different between the two groups. Circulating anti
      WSP antibody titres were markedly lower in both treatment groups when compared to
      control D. immitis infected dogs, indicating that doxycycline is able to reduce
      Wolbachia and prevent the immune response against the bacteria. The combination
      treatment protocol has been shown to be highly adulticidal and further studies
      are needed to better understand the interaction between doxycycline and
      ivermectin in D. immitis infected dogs. 

PMID- 25769473
TI  - Modulation of Marangoni convection in liquid films.
AB  - Non-isothermal liquid films are subject to short- and long-wave modes of
      Marangoni instability. The short-wave instability leads to the development of
      convection cells, whereas long-wave instability is one of the primary causes of
      the film rupture. In this paper different methods for modulation of Marangoni
      convection and Marangoni-induced interface deformation in non-isotherm liquid
      films are reviewed. These methods include modification of substrates through
      topographical features, using substrates with non-uniform thermal properties, non
      uniform radiative heating of the liquid-gas interface and non-uniform heating of
      substrates. All these approaches aim at promotion of temperature gradients along
      the liquid-gas interface, which leads to emergence of thermocapillary stresses,
      to the development of vortices and to the interface deformation. Finally,
      Marangoni convection in a liquid film supported by a substrate with periodic
      temperature distribution is modeled by solution of steady state creeping flow
      equations. This approach is justified for low Reynolds numbers and for Marangoni
      convection in liquids with high Prandtl numbers. The model predicts interaction
      between Marangoni convection induced by non-uniform wall heating and the
      Marangoni short-wave instability. 

PMID- 25769474
TI  - [New populations with increased cardiovascular risk].

PMID- 25769475
TI  - Patient participation in nursing care on medical wards: An integrative review.
AB  - BACKGROUND: Patient participation is a way for patients to engage in their
      nursing care. In view of the possible link between patient participation and
      safety, there is a need for an updated review to assess patient participation in
      nursing care. OBJECTIVES: To investigate patients' and nurses' perceptions of and
      behaviours towards patient participation in nursing care in the context of
      hospital medical wards. DESIGN: Integrative review. DATA SOURCES: Three search
      strategies were employed in August 2013; a computerised database search of
      Cumulative Index of Nursing and Allied Health Literature, Cochrane Library,
      Medline and PsychINFO; reference lists were hand-searched; and forward citation
      searching was executed. REVIEW METHODS: After reviewing the studies, extracting
      study data and completing summary tables the methodological quality was assessed
      using the Mixed-Methods Assessment Tool by two reviewers. Reviewers met then to
      discuss discrepancies as well as the overall strengths and limitations of the
      studies. Discrepancies were overcome through consensus or a third reviewer
      adjudicated the issue. Within and across study analysis and synthesis of the
      findings sections was undertaken using thematic synthesis. RESULTS: Eight studies
      met inclusion criteria. Four themes were identified - enacting participation,
      challenges to participation, promoting participation and types of participation.
      Most studies included were conducted in Europe. The majority of studies used
      qualitative methodologies, with all studies sampling patients; nurses were
      included in three studies. Data were largely collected using self-reported
      perceptions; two studies included observational data. Methodological issues
      included a lack of reflexivity, un-validated data collection tools, sampling
      issues and low response rates. CONCLUSIONS: On medical wards, patients and nurses
      desire, perceive or enact patient participation passively. Challenging factors
      for patient participation include patients' willingness, nurses' approach and
      confusion around expectations and roles. Information-sharing was identified as an
      activity that promotes patient participation, suggesting nurses encourage active
      communication with patients in practice. Involving patients in assessment and
      care planning may also enhance patient participation. For education, enhancing
      nurses' understanding of the attributes of patient participation, as well as
      patient-centred care approaches may be beneficial for medical ward nurses. From
      here, researchers need to examine ways to overcome the barriers to patient
      participation; further nurse participants and observational data is required on
      medical wards.

PMID- 25769476
TI  - Associations between the treatments and outcomes of patients with upper and lower
      lymphoedema in Japan: a cross-sectional observational study.
AB  - BACKGROUND: Lymphoedema is not currently curable, and it is important that
      symptoms are alleviated by appropriate treatment. Treatments aim to delay the
      progression of swelling and to improve patients' quality of life (QOL). There are
      many objective and subjective outcomes of lymphoedema, but it is unclear which
      outcomes should be used to evaluate lymphoedema treatments. OBJECTIVE: This study
      aimed to examine the associations between lymphoedema treatments and outcomes.
      DESIGN: A cross-sectional observational study. SETTING: Lymphoedema outpatient
      clinics in Japan. PARTICIPANTS: A total of 170 patients with lymphoedema were
      recruited from four outpatient clinics. METHODS: The data were collected from
      medical records, physical assessments, and interviews. The following objective
      outcomes were evaluated: circumference measurements, Stemmer sign, cellulitis,
      and skin hardness. The following subjective outcomes were evaluated: satisfaction
      with treatment, subjective symptoms, EuroQol-5 dimensions, and a quality of life
      measure for limb lymphoedema (LYMQOL). Multiple regression analysis was performed
      to examine the associations between lymphoedema treatments and their outcomes.
      RESULTS: Secondary lymphoedema was present in 158 patients (92.9%), and 91
      patients (53.5%) had lower lymphoedema. The patients using compression garments
      were 2.63 times more likely to have a positive Stemmer sign and 2.85 times more
      likely to be satisfied with their treatment than those who were not using
      compression garments (p=0.02 for Stemmer sign, p<0.01 for satisfaction). The
      patients treated with simple lymphatic drainage (SLD) exhibited a 2.26-fold
      greater level of satisfaction with treatment than those not receiving this
      treatment (p<0.01). The patients treated with complete decongestive therapy (CDT)
      had higher QOL than did those not receiving this therapy (beta=-0.19, p=0.04).
      CONCLUSIONS: The progression of swelling can be evaluated using the Stemmer sign
      with regard to compression therapy. The degree of satisfaction can be evaluated
      as the patient's satisfaction with their lymphoedema regarding compression
      garments and SLD, and improvements in QOL can be evaluated using the LYMQOL with
      regard to CDT. The subjective outcomes were not associated with every lymphoedema
      treatment in this study, and the effectiveness of lymphoedema treatment can be
      evaluated using several different outcomes.

PMID- 25769477
TI  - Predictive validity of the START for unauthorised leave and substance abuse in a
      secure mental health setting: a pseudo-prospective cohort study.
AB  - BACKGROUND: Risk assessment and management is central to the nursing role in
      forensic mental health settings. The Short Term Assessment of Risk and
      Treatability (START) aims to support assessment through identification of risk
      and protective factors. It has demonstrated predictive validity for aggression;
      it also aims to aid risk assessment for unauthorised leave and substance abuse
      where its performance is relatively untested. OBJECTIVES: To test the predictive
      validity of the START for unauthorised leave and substance abuse. DESIGN: A
      naturalistic, pseudo-prospective cohort study. SETTINGS: Four centres of a large
      UK provider of secure inpatient mental health services. PARTICIPANTS: Inpatients
      resident between May 2011 and October 2013 who remained in the service for 3
      months following assessment with the START by their clinical team. Exclusion
      criteria were missing assessment data in excess of prorating guidelines. Of 900
      eligible patients 73 were excluded leaving a final sample size of n=827 (response
      rate 91.9%). Mean age was 38.5 years (SD=16.7); most participants (72.2%) were
      male; common diagnoses were schizophrenia-type disorders, personality disorders,
      organic disorders, developmental disorders and intellectual disability. METHODS:
      Routinely conducted START assessments were gathered. Subsequent incidents of
      substance abuse and unauthorised leave were coded independently. Positive and
      negative predictive values of low and elevated risk were calculated. Receiver
      Operating Characteristic analysis was conducted to ascertain the predictive
      accuracy of the assessments based on their sensitivity and specificity. RESULTS:
      Patient-based rates of unauthorised leave (2.4%) and substance abuse (1.6%) were
      low. The positive and negative predictive values for unauthorised leave were 5.9%
      and 98.4%; and for substance abuse 8.1% and 99.0%. The START specific risk
      estimate for unauthorised leave predicted its associated outcome (Area under the
      curve=.659, p<.05, 95% CI .531, .786); the substance abuse risk estimate
      predicted its outcome with a large effect size (Area under the curve=.723, p<.01,
      95% CI .568, .879). CONCLUSIONS: The study provides limited support for the START
      by demonstrating the predictive validity of its specific risk estimates for
      substance abuse and unauthorised leave. High negative predictive values suggest
      the tool may be of most utility in screening out low risk individuals from
      unnecessary restrictive interventions; very low positive predictive values
      suggest caution before implementing restrictive interventions in those rated at
      elevated risk. Researchers should investigate how multidisciplinary teams
      formulate risk assessments for these outcomes since they outperform the
      quantitative element of this tool.

PMID- 25769478
TI  - Long-term consequences of adolescent parenthood among African-American urban
      youth: a propensity score matching approach.
AB  - PURPOSE: The aim of this study was to improve understanding of long-term
      socioeconomic consequences of teen parenting for men and women. METHODS: Analysis
      is based on the Woodlawn Study, a longitudinal study of an African-American
      cohort from a socially disadvantaged community in Chicago; data were collected at
      childhood (N = 1,242), adolescence (N = 705), young adulthood (age 32 years, N =
      952), and midlife (age 42 years, N = 833). This analysis focused on the 1,050
      individuals with data on teen parenting. We used propensity score matching to
      account for differences in background characteristics between teenage parents and
      their peers and used multiple imputation to account for differential attrition.
      RESULTS: The regression models after propensity score matching showed that at the
      age of 32 years, in comparison to nonteen mothers, teenage mothers were more
      likely to be unemployed, live in poverty, depend on welfare, and have earned a
      GED or completed high school compared to finishing college. At the age of 32
      years, teen fathers were more likely to be without a job than nonteen fathers. At
      the age of 42 years, the effect of teen parenting for women remained
      statistically significant for education and income. There were no significant
      associations between teen parenting and outcomes for men at the age of 42 years.
      CONCLUSIONS: Socioeconomic consequences of teenage parenting among African
      Americans from disadvantaged background seem to be primarily concentrated in
      women and persist throughout adulthood. In addition to promoting the delay of
      parenting after the teenage years, it is critical to provide programs at early
      stages in the life course to mitigate the negative socioeconomic consequences of
      teenage motherhood as effects for women are broad.

PMID- 25769479
TI  - Outcome After Arthroscopic Decompression of Inferior Labral Cysts Combined With
      Labral Repair.
AB  - PURPOSE: To analyze the clinical and radiologic outcomes of arthroscopic cyst
      decompression and labral repair in patients with inferior paralabral cysts with
      chronic shoulder pain. METHODS: Between March 2006 and September 2012, 16
      patients who were identified as having inferior paralabral cysts presented with
      chronic shoulder pain. All patients underwent a thorough physical examination and
      preoperative magnetic resonance arthrographic evaluation. The mean age was 30
      years (range, 17 to 50 years). The mean follow-up period was 38 months (range, 16
      to 60 months). Clinical outcome scores (American Shoulder and Elbow Surgeons;
      University of California, Los Angeles; and Simple Shoulder Test) and passive
      shoulder range of motion were evaluated at last follow-up. Follow-up magnetic
      resonance imaging was performed at a mean of 8 months to determine the labral
      healing status and assess for cyst recurrence. RESULTS: The incidence of isolated
      inferior paralabral cysts was 0.6% (16 of 2,656 cases). Of the patients, 8 had
      multiple cysts and 8 had a single cyst. The mean length and width of the cysts
      were 1.0 cm and 0.4 cm, respectively. Eight cases had a history of trauma, and 13
      patients were involved in sports activities. Seventy-five percent of cases showed
      a positive relocation test. The mean American Shoulder and Elbow Surgeons;
      University of California, Los Angeles; and Simple Shoulder Test scores improved
      from 64, 22, and 8.7, respectively, preoperatively to 83, 31, and 10,
      respectively (P < .001), at final follow-up. Shoulder range of motion did not
      show any significant improvement. The location of the labral tear was as follows:
      anteroinferior tear in 5 cases, posteroinferior tear in 8 cases, and combined
      anteroinferior and posteroinferior tear in 3 cases. All cysts were found to be in
      association with a labral tear. A mean of 2.7 anchors were used for inferior
      labral repair. These cysts were found only in male patients. None of the patients
      showed any evidence of cyst recurrence on follow-up magnetic resonance imaging.
      CONCLUSIONS: Inferior labral tears treated with cyst decompression and labral
      repair showed satisfactory clinical results without any recurrence. Inferior
      paralabral cysts should be considered in the differential diagnosis in patients
      presenting with chronic shoulder pain, particularly active male patients. LEVEL
      OF EVIDENCE: Level IV, therapeutic case series.

PMID- 25769480
TI  - Platelet-Rich Plasma Inhibits Mechanically Induced Injury in Chondrocytes.
AB  - PURPOSE: To investigate the effect of platelet-rich plasma (PRP) on mechanically
      injured chondrocytes. METHODS: PRP from bovine whole blood was activated to
      prepare platelet-rich plasma releasate (PRPr). Bovine articular chondrocytes were
      subjected to 16%, 0.5-Hz biaxial cyclic tensile strain (CTS) for 48 hours and
      cultured for another 24 hours without cell stretching as an in vitro model of
      mechanically injured chondrocytes. Culture medium in the 3 PRP- and CTS-treated
      groups was supplemented with 10% PRPr at the start of CTS, after 24 hours of CTS,
      and after 48 hours of CTS, respectively. Gene expression levels of type II
      collagen, aggrecan, matrix metalloproteinase (MMP)-3, MMP-13, inducible nitric
      oxide synthase, and cyclooxygenase 2 were quantitatively evaluated. Changes in
      the content of nitric oxide (NO), prostaglandin E2 (PGE2), MMP-3, and tissue
      inhibitor of metalloproteinase 1 in the culture medium were also measured.
      RESULTS: PRPr increased type II collagen and aggrecan messenger RNA expression;
      diminished CTS-dependent up-regulation of MMP-3, inducible nitric oxide synthase,
      and cyclooxygenase 2 gene expression; and reduced CTS-induced overproduction of
      NO and PGE2 when PRPr was applied early at the start of CTS. The addition of PRPr
      after 24 hours of CTS only inhibited MMP-3 gene up-regulation and the increase of
      NO and PGE2 induced by CTS. These changes were not observed when PRPr was
      supplemented after 48 hours of CTS. PRPr mitigated the increased MMP-3 production
      and decreased tissue inhibitor of metalloproteinase 1 secretion resulting from
      CTS in a time-dependent manner. CONCLUSIONS: PRP treatment ameliorated multiple
      CTS-mediated catabolic and inflammatory responses in chondrocytes. More
      beneficial effects were observed with early PRP application. CLINICAL RELEVANCE:
      Intra-articular PRP injections at the beginning of strenuous exercises may be
      used to protect chondrocytes from mechanical injury, thus preventing joints from
      increased wear.

PMID- 25769481
TI  - Quadriceps Strength and Endurance After Posterior Cruciate Ligament Tears Versus
      Matched Group With Anterior Cruciate Ligament Tears.
AB  - PURPOSE: This study was designed to compare the preoperative strengths and
      endurances of the quadriceps and hamstring muscles in patients with anterior
      cruciate ligament (ACL) versus posterior cruciate ligament (PCL) tears. METHODS:
      Quadriceps and hamstring muscle strength and endurance were compared between 20
      prospectively enrolled patients with isolated PCL tears and a retrospective,
      matched control group of 20 patients with isolated ACL tears. The maximal torque
      (60 degrees /s) and total work (180 degrees /s) of the quadriceps and hamstring
      were evaluated with an isokinetic testing device. RESULTS: Total work (1,094.4 +/
      505.8 J v 797.5 +/- 332.7 J, P = .035) and peak torque (129.9 +/- 56.2 N ? m v
      98.2 +/- 37.4 N ? m, P = .046) of the quadriceps muscle on the involved side were
      higher in the PCL tear group than in the ACL tear group. However, there were no
      significant differences between the PCL tear group and ACL tear group in
      hamstring muscle strength (45.8 +/- 42.3 N ? m and 46.0 +/- 24.4 N ? m,
      respectively; P = .940) and endurance (429.3 +/- 238.9 J and 382.4 +/- 256.1 J,
      respectively; P = .574) on the involved side. CONCLUSIONS: The strength and
      endurance of the quadriceps muscle of the injured limb were greater after PCL
      tears than after ACL tears. However, there were no significant between-group
      differences in hamstring muscle strength and endurance on the involved side.
      LEVEL OF EVIDENCE: Level III, retrospective comparative study.

PMID- 25769482
TI  - Biomechanical Comparisons of Pull Out Strengths After Pedicle Screw Augmentation
      with Hydroxyapatite, Calcium Phosphate, or Polymethylmethacrylate in the
      Cadaveric Spine.
AB  - OBJECTIVE: In vertebrae with low bone mineral densities pull out strength is
      often poor, thus various substances have been used to fill screw holes before
      screw placement for corrective spine surgery. We performed biomechanical
      cadaveric studies to compare nonaugmented pedicle screws versus hydroxyapatite,
      calcium phosphate, or polymethylmethacrylate augmented pedicle screws for screw
      tightening torques and pull out strengths in spine procedures requiring bone
      screw insertion. METHODS: Seven human cadaveric T10-L1 spines with 28 vertebral
      bodies were examined by x-ray to exclude bony abnormalities. Dual-energy x-ray
      absorptiometry scans evaluated bone mineral densities. Twenty of 28 vertebrae
      underwent ipsilateral fluoroscopic placement of 6-mm holes augmented with
      hydroxyapatite, calcium phosphate, or polymethylmethacrylate, followed by
      transpedicular screw placements. Controls were pedicle screw placements in the
      contralateral hemivertebrae without augmentation. All groups were evaluated for
      axial pull out strength using a biomechanical loading frame. RESULTS: Mean
      pedicle screw axial pull out strength compared with controls increased by 12.5%
      in hydroxyapatite augmented hemivertebrae (P = 0.600) and by 14.9% in calcium
      phosphate augmented hemivertebrae (P = 0.234), but the increase was not
      significant for either method. Pull out strength of polymethylmethacrylate versus
      hydroxyapatite augmented pedicle screws was 60.8% higher (P = 0.028).
      CONCLUSIONS: Hydroxyapatite and calcium phosphate augmentation in osteoporotic
      vertebrae showed a trend toward increased pedicle screw pull out strength versus
      controls. Pedicle screw pull out force of polymethylmethacrylate in the insertion
      stage was higher than that of hydroxyapatite. However, hydroxyapatite is likely a
      better clinical alternative to polymethylmethacrylate, as hydroxyapatite
      augmentation, unlike polymethylmethacrylate augmentation, stimulates bone growth
      and can be revised.

PMID- 25769483
TI  - Spinal Intradural Aneurysmal Bone Cyst: A Case Report.

PMID- 25769484
TI  - Alternating electric fields and carcinogenesis: a new paradigm to avoid missing
      the elephant in the room.

PMID- 25769485
TI  - Vancomycin Powder in Spine Surgery: Still a Work in Progress.

PMID- 25769486
TI  - Decision Making for Patients With Concomitant Pituitary Macroadenoma and
      Ophthalmologic Comorbidity: A Clinical Controversy.
AB  - BACKGROUND: Coexisting complex visual field defects and serious ophthalmologic
      comorbidities make the management of the pituitary macroadenomas more
      challenging. Diffusion tensor imaging (DTI) magnetic resonance imaging that
      tracks neural fibers in the white matter has been used recently to visualize the
      impact of different pathologies on cranial nerves. This study explains
      application of anterior optic pathway tractography for patients with
      ophthalmologic comorbidities and pituitary adenoma. METHODS: Two patients with
      atypical visual field defects caused by nonfunctional pituitary macroadenoma and
      simultaneous ophthalmologic morbidities (one glaucoma and the other giant cell
      arteritis) were selected for surgical decompression of the anterior optic
      apparatus. Standard perimetry and optic pathway DTI were done preoperatively,
      intraoperatively, and 3 months after surgery. RESULTS: The nontypical pattern of
      visual field defect could not differentiate between the ophthalmologic disease
      and the chiasmatic compression attributable to pituitary macroadenoma as the main
      cause. Preoperative visual pathway DTI tractography showed lack of decussating
      chiasmatic fibers in both of the patients. DTI tractography revealed the
      reappearance of these fibers intraoperatively in one and postoperatively in the
      other one. Three months after surgery, the visual field and acuity improved and
      DTI tractography confirmed presence of crossing chiasmatic fibers. CONCLUSION:
      Visual pathway DTI tractography is a promising adjunct to the standard perimetry
      in preoperative assessment of pituitary macroadenoma with serious ophthalmologic
      comorbidities. It also may be useful in the intraoperative determination of the
      optic pathway decompression and for following the visual outcome of these
      patients after surgery.

PMID- 25769487
TI  - Adjacent Level Ligamentous Injury Associated with Traumatic Cervical Spine
      Fractures: Indications for Imaging and Implications for Treatment.
AB  - BACKGROUND: Magnetic resonance imaging (MRI) is a vital tool for detection of
      soft tissue injury (STI) after cervical spine injury (CSI). However, high cost,
      prolonged imaging time, and limited use in hemodynamically unstable patients
      necessitates that the utility of MRI in all patients with CSI be scrutinized.
      METHODS: A retrospective review was performed of all patients treated for a CSI
      at a Level I trauma center between 2005 and 2010. Patient demographics, fracture
      characteristics, and associated STIs were collected. STIs were classified further
      into same level ligamentous injury, adjacent level ligamentous injury (ALLI),
      cord contusion, and traumatic herniated disc. ALLI was defined as anterior or
      posterior longitudinal ligament, ligamentum flavum, or supraspinous or
      interspinous ligamentous injury. RESULTS: MRI was performed in 240 of 787
      patients. Evidence of STI was identified in 54.6%. ALLI was the most common STI
      (80 of 240 patients); these injuries were subdivided into above, below, or both
      above and below the concurrent fracture level. Patients with ALLI were
      significantly more likely to have injured C3 (P < 0.01) and C5 (P < 0.03) levels,
      association with widened disc space (P = 0.03), and multiple CSIs (P = 0.008).
      The whole ALLI was included in the fixation strategy in 100% of patients with
      ALLI only above the concurrent fracture level and 87% of patients with ALLI only
      below the concurrent fracture level. CONCLUSIONS: MRI detected an associated STI
      in about 55% of patients who underwent imaging. Injuries involving multiple
      fractured cervical levels, fractures at C3 and C5, and widened disc space should
      raise the treating physician's level of suspicion for ALLI. Our data show that
      treatment directed by MRI findings in select cases has substantial value.

PMID- 25769489
TI  - Doctors should not cherry pick what information to give patients, court rules.

PMID- 25769488
TI  - The Influence of Adjuvant Radiotherapy in Atypical and Anaplastic Meningiomas: A
      Series of 88 Patients in a Single Institution.
AB  - OBJECTIVE: Atypical and anaplastic meningiomas (World Health Organization
      classification grade II and III) represent a small and heterogeneous subgroup of
      meningiomas that has a more aggressive biological nature and higher frequency of
      recurrence. The atypical form accounts for 4.7%-7.2%, whereas the anaplastic type
      accounts for 1%-2.8% of all meningiomas. The aim of this study is to evaluate the
      role of postoperative radiotherapy on overall survival and progression-free
      survival in patients operated for atypical and anaplastic meningiomas. METHODS: A
      retrospective analysis of the patients operated at the Clinic of Neurosurgery,
      Clinical Center of Serbia, Belgrade, between January 1, 1995 and December 31,
      2006 was performed. In that period 88 lesions met the histologic criteria for
      atypical (75) and anaplastic (13) meningiomas. Postoperative radiotherapy was
      conducted in 63.6% of patients. RESULTS: At a median follow-up of 67.4 months the
      overall survival was 68 months and the 5-year survival was about 54.5%. The
      median survival was 76 months with surgery and adjuvant radiotherapy and 40
      months with surgery alone (log rank = 7.4; P = 0.006). Recurrent disease occurred
      in 58 patients (65.9%). Median time between first surgery and tumor recurrence in
      patients undergoing radiotherapy was 51 months, whereas in the nonirradiated
      group it was 24 months (log rank = 17.7; P < 0.001). Multivariate analysis
      identified as recurrence-predicting factors anaplastic histotype (hazard ratio =
      2.9; P = 0.003) and postoperative radiotherapy (hazard ratio = 4.5; P < 0.001).
      CONCLUSIONS: The addition of adjuvant radiotherapy to surgery for atypical and
      anaplastic meningiomas resulted in a clinically meaningful and statistically
      significant survival benefit.

PMID- 25769490
TI  - Blunted autonomic response in cluster headache patients.
AB  - BACKGROUND: Cluster headache (CH) is a disabling headache disorder with
      chronobiological features. The posterior hypothalamus is involved in CH
      pathophysiology and is a hub for autonomic control. We studied autonomic response
      to the head-up tilt table test (HUT) including heart rate variability (HRV) in CH
      patients and compared results to healthy controls. METHODS AND MATERIALS: Twenty
      seven episodic and chronic CH patients and an equal number of age-, sex- and BMI
      matched controls were included. We analyzed responses to HUT in the time and
      frequency domain and by non-linear analysis. RESULTS: CH patients have normal
      cardiovascular responses compared to controls but increased blood pressure. In
      the frequency analysis CH patients had a smaller change in the normalized low-
      (LF) (2.89 vs. 13.38, p < 0.05) and high-frequency (HF) (-2.86 vs. -13.38, p <
      0.05) components as well as the LF/HF ratio (0.81 vs. 2.62, p < 0.05) in response
      to tilt. In the Poincare plot, the change in ratio between long- and short-term
      variation was lower in patients (SD1/SD2, -0.05 vs. -0.17, p < 0.05).
      CONCLUSIONS: CH patients show decreased autonomic response to HUT compared to
      healthy controls. This can be interpreted as dysregulation in the posterior
      hypothalamus and supports a theory of central autonomic mechanisms involvement in
      CH.

PMID- 25769491
TI  - Beneficial and side effects of arginine vasopressin and terlipressin for septic
      shock.
AB  - Arginine vasopressin (AVP) and its analog, terlipressin (TP), were all
      demonstrated beneficial for septic shock. What advantages and disadvantages that
      AVP and TP have for septic shock as well as the mechanism, however, are not
      completely known. With cecal ligation and puncture-induced septic shock rats and
      lipopolysaccharide-induced septic shock rabbits, we systematically compared the
      beneficial and side effects of AVP and TP, in septic shock and the sex
      difference, and investigated their relationship to Rho kinase and calcium
      sensitivity. The results indicated that low dose of TP (2.6 MUg/kg/h) in
      combination with norepinephrine (NE) improving vascular reactivity and animal
      survival were superior to a small dose of AVP (0.03 U/kg/h) in septic shock rats
      and rabbits. This improving effect of AVP and TP on vascular reactivity was
      closely related to the activation of Rho-kinase and Rho-kinase-mediating vascular
      calcium sensitization. A small dose of TP did not result in hyponatremia, did not
      increase blood bilirubin and decrease platelet count, whereas AVP did. Animal
      survival and vascular reactivity in female rats after TP or AVP administration
      were slightly better than male rats, while there were no significant differences.
      It was suggested that a small dose of TP has better beneficial effect and less
      side effects on septic shock than AVP. AVP and TP improving vascular reactivity
      is closely related to Rho-kinase activation and calcium sensitivity improvement.
      TP or plus NE may be more appropriate for early emergency care for severe septic
      shock than AVP.

PMID- 25769492
TI  - Comparison of First- and Second-Generation Fixed-Bearing Total Ankle Arthroplasty
      Using a Modular Intramedullary Tibial Component.
AB  - BACKGROUND: This series reviews the clinical and radiographic outcomes of
      patients who underwent total ankle replacement (TAR) using first- and second
      generations of a modern fixed-bearing prosthesis utilizing a modular
      intramedullary stem. METHODS: A consecutive series of first- and second
      generation primary TARs with modular intramedullary stems were identified.
      Clinical outcome data were collected prospectively--including visual analog scale
      for pain, American Orthopaedic Foot & Ankle Society hindfoot-ankle, Short
      Musculoskeletal Function Assessment, and Short Form-36 scores. Preoperative
      coronal plane deformity and correction of deformity after TAR were assessed.
      Complications, subsequent procedures, and failure rates were compared. A total of
      193 first- and 56 second-generation patients were identified with a mean follow
      up of 3.7 and 2.1 years, respectively. RESULTS: Clinical outcome data reflected
      significant improvements at 1 year postoperatively, and improvements were
      maintained at 2-year follow-up for each group. Improvement in visual analog scale
      scores were significantly better in the second-generation group at 1 year
      postoperatively, but this was not maintained at 2 years. Mean coronal tibiotalar
      angles for ankles with preoperative varus or valgus deformities were
      significantly improved. Correction was maintained until final follow-up, with no
      significant differences in deformity improvement between groups. The rate of
      reoperation at 2 years postoperatively on the affected foot or ankle subsequent
      to the index ankle replacement for patients in the first-generation group (18.5%)
      was higher compared to the second-generation group (15.9%), but the time until
      reoperation was not statistically significant (P = .376). The implant failure
      rate was higher in the first-generation group (6.0%) compared to the second
      generation group (2.6%) at 2 years postoperatively, but the time until failure
      was not significantly different (P = .295). CONCLUSION: Patients who underwent
      TAR with a first- or second-generation fixed-bearing prosthesis with an
      intramedullary tibial component demonstrated significant improvements in all
      measures of pain and function with sustained improvements in coronal plane
      alignment. The second-generation prosthesis demonstrated slightly better
      improvements at 1 year and was associated with lower reoperation and implant
      failure rates. LEVEL OF EVIDENCE: Level II, comparative series.

PMID- 25769493
TI  - Impact of 6 % hydroxyethyl starch (HES) 130/0.4 on the correlation between
      standard laboratory tests and thromboelastography (TEG(r)) after cardiopulmonary
      bypass.
AB  - BACKGROUND: Hydroxyethyl starches (HES) affect the results of thromboelastography
      (TEG(r)). We sought to determine whether using HES rather than crystalloids for
      cardiopulmonary bypass (CPB) prime and intraoperative fluid therapy changes the
      TEG cutoff values best identifying patients with a low platelet count or a low
      fibrinogen level after CPB. METHODS: Data from 96 patients who had on-pump
      cardiac surgery, a TEG(r) (kaolin-heparinase) and standard investigations of
      blood clotting performed after separation from CPB and protamine administration
      were retrospectively reviewed. Patients were assigned to the HES or crystalloid
      group according to whether balanced 6% HES 130/0.4 or balanced crystalloids were
      used for intraoperative fluid therapy and pump prime. Mutlivariable linear
      regression models with computation of the standardized regression coefficients
      were used to identify independent associations between the four main TEG
      parameters (R time, alpha angle, K time and MA) and the type of fluid used, the
      INR, the aPTT, the fibrinogen level and the platelet count. Receiver-operating
      characteristic curves were used to assess the effect of HES on the ability of TEG
      parameters to identify patients with a platelet count<80.000MUl(-1) or a
      fibrinogen level<1.5 gr l(-1) and on the cutoff values best identifying these
      patients. RESULTS: The type of fluid used significantly affected the MA
      (P<0.001), the K time (P<0.001) and the alpha angle (P<0.001) regardless of the
      results of the standard clotting tests. According to standardized beta regression
      coefficients the platelet count and the type of fluid used were stronger
      predictors of the MA, the alpha angle and the K time than the fibrinogen level.
      MA better predicted platelets<80.000MUl(-1) than K time and alpha angle
      (P=0.023). The best cutoff value of MA identifying patients with
      platelets<80.000MUl(-1) was 62mm in the crystalloid group and 53mm in the HES
      group. MA, K time and alpha angle were poor predictors of the postoperative
      fibrinogen level. CONCLUSION: HES significantly changes the cutoff value of
      TEG(r) MA best identifying patients<80.000MUl(-1) after on-pump cardiac surgery.

PMID- 25769496
TI  - The effect of different graphical and numerical likelihood formats on perception
      of likelihood and choice.
AB  - BACKGROUND: Quantitative risk information plays an important role in decision
      making about health. This study focuses on commonly used numerical and graphical
      formats and examines their effect on perception of different likelihoods and
      choice preferences. METHODS: An experimental study was conducted with 192
      participants, who evaluated 2 sets of 4 lotteries. Numerical formats to describe
      likelihood varied systematically between participants (X%, X-in-100, or 1-in-X).
      The effect of graphic formats (bar charts, icon charts) was assessed as a within
      subjects factor. Dependent measures included perceived likelihood, choice
      preferences about participating in the lottery, and processing times. RESULTS:
      Numerical likelihoods presented as 1-in-X were processed fastest and were
      perceived as conveying larger likelihoods than the X-in-100 and percentages
      formats (mean response times in seconds: 5.65 v. 7.31 and 6.50; mean rating on a
      1-9 scale: 4.38 v. 3.30 and 3.31, respectively). The 1-in-X format also evoked a
      stronger willingness to participate in a lottery than the 2 other numerical
      formats. The effect of adding graphs on perceived likelihood was moderated by
      numerical aptitude. Graphs reduced ratings of perceived likelihood of
      participants with lower numeracy, while there was no overall effect for
      participants with higher numeracy. CONCLUSION: Perception of likelihood differs
      significantly depending on the numerical format used. The 1-in-X format yields
      higher perceived likelihoods and it appears to be the easiest format to
      interpret. Graphs primarily affect perception of likelihood of people with lower
      numerical aptitude. These effects should be taken into account when discussing
      medical risks with patients.

PMID- 25769495
TI  - Tumour necrosis factor inhibitors versus combination intensive therapy with
      conventional disease modifying anti-rheumatic drugs in established rheumatoid
      arthritis: TACIT non-inferiority randomised controlled trial.
AB  - OBJECTIVE: To determine whether intensive combinations of synthetic disease
      modifying drugs can achieve similar clinical benefits at lower costs to high cost
      biologics such as tumour necrosis factor inhibitors in patients with active
      rheumatoid arthritis resistant to initial methotrexate and other synthetic
      disease modifying drugs. DESIGN: Open label pragmatic randomised multicentre two
      arm non-inferiority trial over 12 months. SETTING: 24 rheumatology clinics in
      England. PARTICIPANTS: Patients with rheumatoid arthritis who were eligible for
      treatment with tumour necrosis factor inhibitors according to current English
      guidance were randomised to either the tumour necrosis factor inhibitor strategy
      or the combined disease modifying drug strategy. INTERVENTIONS: Biologic
      strategy: start tumour necrosis factor inhibitor; second biologic in six month
      for non-responders. Alternative strategy: start combination of disease modifying
      drugs; start tumour necrosis factor inhibitors after six months in non
      responders. MAIN OUTCOME MEASURE:  PRIMARY OUTCOME: reduction in disability at 12
      months measured with patient recorded heath assessment questionnaire (range 0.00
      3.00) with a 0.22 non-inferiority margin for combination treatment versus the
      biologic strategy. SECONDARY OUTCOMES: quality of life, joint damage, disease
      activity, adverse events, and costs. Intention to treat analysis used multiple
      imputation methods for missing data. RESULTS: 432 patients were screened: 107
      were randomised to tumour necrosis factor inhibitors and 101 started taking; 107
      were randomised to the combined drug strategy and 104 started taking the drugs.
      Initial assessments were similar; 16 patients were lost to follow-up (seven with
      the tumour necrosis factor inhibitor strategy, nine with the combined drug
      strategy); 42 discontinued the intervention but were followed-up (19 and 23,
      respectively). The primary outcome showed mean falls in scores on the health
      assessment questionnaire of -0.30 with the tumour necrosis factor inhibitor
      strategy and -0.45 with the alternative combined drug strategy. The difference
      between groups in unadjusted linear regression analysis favoured the alternative
      strategy of combined drugs. The mean difference was -0.14, and the 95% confidence
      interval (-0.29 to 0.01) was below the prespecified non-inferiority boundary of
      0.22. Improvements at 12 months in secondary outcomes, including quality of life
      and erosive progression, were similar with both strategies. Initial reductions in
      disease activity were greater with the biologic strategy, but these differences
      did not persist beyond six months. Remission was seen in 72 patients (44 with
      biologic strategy; 36 with alternative strategy); 28 patients had serious adverse
      events (18 and 10, respectively); six and 10 patients, respectively, stopped
      treatment because of toxicity. The alternative strategy reduced health and social
      care costs per patient by L3615 (?4930, $5585) for months 0-6 and L1930 for
      months 6-12. CONCLUSIONS: In patients with active rheumatoid arthritis who meet
      English criteria for biologics an alternative strategy with combinations of
      intensive synthetic disease modifying drugs gives non-inferior outcomes to
      treatment with tumour necrosis factor inhibitors. Costs are reduced
      substantially.Trial Registration ISRCTN 37438295.

PMID- 25769497
TI  - Epigenetic inheritance and evolution: A paternal perspective on dietary
      influences.
AB  - The earliest indications for paternally induced transgenerational effects from
      the environment to future generations were based on a small number of long-term
      epidemiological studies and some empirical observations. Only recently have
      experimental animal models and a few analyses on human data explored the
      transgenerational nature of phenotypic changes observed in offspring. Changes
      include multiple metabolic disorders, cancer and other chronic diseases. These
      phenotypes cannot always be explained by Mendelian inheritance, DNA mutations or
      genetic damage. Hence, a new compelling theory on epigenetic inheritance is
      gaining interest, providing new concepts that extend Darwin's evolutionary
      theory. Epigenetic alterations or "epimutations" are being considered to explain
      transgenerational inheritance of parentally acquired traits. The responsible
      mechanisms for these epimutations include DNA methylation, histone modification,
      and RNA-mediated effects. This review explores the literature on a number of time
      dependent environmentally induced epigenetic alterations, specifically those from
      dietary exposures. We suggest a role for the male germ line as one of nature's
      tools to capture messages from our continuously changing environment and to
      transfer this information to subsequent generations. Further, we open the
      discussion that the paternally inherited epigenetic information may contribute to
      evolutionary adaptation. 

PMID- 25769494
TI  - A recombinant fragment of von Willebrand factor reduces fibrin-rich microthrombi
      formation in mice with endotoxemia.
AB  - INTRODUCTION: Disseminated fibrin deposition in the microvasculature such as in
      disseminated intravascular coagulation (DIC) arises from uninhibited activated
      coagulation secondary to sustained systemic inflammation. Currently there is no
      treatment for DIC. Treating the underlying trigger and supportive care are the
      current recommendations to manage DIC. This study aims at using recombinant von
      Willebrand factor (VWF) A2 domain polypeptide to inhibit VWF-mediated platelet
      adhesion to fibrin and prevent DIC. MATERIALS AND METHODS: We use flow chamber
      assay to test the capacity of purified A2 protein to inhibit platelet adhesion to
      immobilized fibrin(ogen) and platelet-fibrin clot formation. We use a murine
      model of lipopolysaccharide-induced DIC to examine the effect of A2 protein on
      DIC. RESULTS: The A2 protein blocked flow-dependent platelet adhesion to fibrin,
      delayed fibrin polymerization, and inhibited platelet-fibrin clot formation in
      vitro. The infusion of the purified A2 protein to the endotoxin-treated mice
      prevented fibrin-rich microthrombi formation in brain, lung, kidney, and liver.
      It also attenuated levels of inflammatory mediators, and markedly reduced
      mortality rates at 96hours. CONCLUSIONS: The A2 protein inhibited platelet
      interaction with fibrin(ogen). Furthermore, A2 prevented disseminated fibrin-rich
      microthrombi and decrease mortality in a lipopolysaccharide-induced DIC murine
      model. A2 could provide a novel therapeutic approach in critically ill patients
      with uninhibited activated coagulation and disseminated fibrin deposition such as
      DIC.

PMID- 25769498
TI  - Visible micro-Raman spectroscopy of single human mammary epithelial cells exposed
      to x-ray radiation.
AB  - A micro-Raman spectroscopy investigation has been performed in vitro on single
      human mammary epithelial cells after irradiation by graded x-ray doses. The
      analysis by principal component analysis (PCA) and interval-PCA (i-PCA) methods
      has allowed us to point out the small differences in the Raman spectra induced by
      irradiation. This experimental approach has enabled us to delineate radiation
      induced changes in protein, nucleic acid, lipid, and carbohydrate content. In
      particular, the dose dependence of PCA and i-PCA components has been analyzed.
      Our results have confirmed that micro-Raman spectroscopy coupled to properly
      chosen data analysis methods is a very sensitive technique to detect early
      molecular changes at the single-cell level following exposure to ionizing
      radiation. This would help in developing innovative approaches to monitor
      radiation cancer radiotherapy outcome so as to reduce the overall radiation dose
      and minimize damage to the surrounding healthy cells, both aspects being of great
      importance in the field of radiation therapy.

PMID- 25769499
TI  - Association of IDH1/2 mutation with preoperative seizure in low-grade gliomas:
      how strong is the evidence?

PMID- 25769500
TI  - Health care use amongst online buyers of medications and vitamins.
AB  - BACKGROUND: With increased use of the internet, more people access medications
      and health supplements online. However little is known about factors associated
      with using online buying. Given the variable quality of online pharmacies, an
      important question is whether online consumers also have health care providers
      with whom they discuss internet information and decisions. OBJECTIVES: To help
      address these gaps this study used the Andersen Model to explore (1) the
      characteristics of internet buyers of medicines and/vitamins, (2) the association
      between health care use and buying medicines and/vitamins online drawing on the
      Andersen health care utilization framework, and (3) factors predicting discussion
      of internet information with health providers. METHODS: The National Cancer
      Institute's Health Information National Trends Survey (HINTS) 2007 was analyzed
      to study online medication buying among a national sample of internet users (N =
      5074). The Andersen Model of health care utilization guided the study's variable
      selection and analyses. Buying online and talking about online information are
      the two main outcome variables. Separate multivariate logistic regression
      analyses identified factors associated with online buying and factors predicting
      discussions with providers about online information. RESULTS: In 2007, 14.5% (n =
      871) of internet users bought a medication or vitamin online. About 85% of online
      buyers had a regular provider, but only 39% talked to the provider about online
      information even though most (93.7%) visited the provider >=1 times/year.
      Multivariate analyses found internet health product consumers were more likely to
      be over 50 years old, have insurance and discuss the internet with their provider
      than non-internet health product consumers. Moreover, discussion of internet
      information was more likely if consumers had a regular provider and perceived
      their communication to be at least fair or good in general. CONCLUSIONS: There is
      a clear association of online buying with age, frequency of visits and discussing
      online information with a provider. Although most online buyers visited a
      provider in the prior year, only a minority discussed the internet with them.
      This suggests a missed opportunity for providers to help patients navigate
      internet buying, particularly if they are a patient's regular provider and the
      patient perceives their communication as good.

PMID- 25769501
TI  - Recent developments toward the safer use of opioids, with a focus on hydrocodone.
AB  - Opioids have become a mainstay of treatment for pain in the United States, with
      over 250 million prescription issued in 2012 alone. The increased prescribing of
      these medications has also contributed to the unintended consequence of a
      widening prevalence of abuse and misuse, and therefore safety has become a top
      agenda item for both government and health care providers alike. The move toward
      new abuse-deterrent formulation technologies, enhanced regulatory requirements
      from the Food and Drug Administration (FDA) and Drug Enforcement Administration
      (DEA), and developments in national/state policies have worked together to target
      a goal of promoting safer clinician prescribing, pharmacy dispensing and patient
      use of opioids. Hydrocodone in particular, as the most widely prescribed opioid
      product, has recently been subject to a myriad of changes, both through the
      federal rescheduling of hydrocodone-combination products (HCPs) to Schedule II,
      as well as the introduction of two new extended-release formulations to the USA
      market. These efforts represent a first step toward tackling the opioid harms
      epidemic, although continuing follow-up through research and policy
      implementation is needed to see any measureable impact on safety in the future.

PMID- 25769502
TI  - Visual attention mitigates information loss in small- and large-scale neural
      codes.
AB  - The visual system transforms complex inputs into robust and parsimonious neural
      codes that efficiently guide behavior. Because neural communication is
      stochastic, the amount of encoded visual information necessarily decreases with
      each synapse. This constraint requires that sensory signals are processed in a
      manner that protects information about relevant stimuli from degradation. Such
      selective processing--or selective attention--is implemented via several
      mechanisms, including neural gain and changes in tuning properties. However,
      examining each of these effects in isolation obscures their joint impact on the
      fidelity of stimulus feature representations by large-scale population codes.
      Instead, large-scale activity patterns can be used to reconstruct representations
      of relevant and irrelevant stimuli, thereby providing a holistic understanding
      about how neuron-level modulations collectively impact stimulus encoding.

PMID- 25769503
TI  - C-reactive protein as a prognostic indicator for rebleeding in patients with
      nonvariceal upper gastrointestinal bleeding.
AB  - BACKGROUND: In patients with acute nonvariceal upper gastrointestinal bleeding,
      rebleeding after an initial treatment is observed in 10-20% and is associated
      with mortality. AIM: To investigate whether the initial serum C-reactive protein
      level could predict the risk of rebleeding in patients with acute nonvariceal
      upper gastrointestinal bleeding. METHODS: This was a retrospective study using
      prospectively collected data for upper gastrointestinal bleeding. Initial
      clinical characteristics, endoscopic features, and C-reactive protein levels were
      compared between those with and without 30-day rebleeding. RESULTS: A total of
      453 patients were included (mean age, 62 years; male, 70.9%). The incidence of 30
      day rebleeding was 15.9%. The mean serum C-reactive protein level was
      significantly higher in these patients than in those without rebleeding
      (P<0.001). The area under the receiver operating characteristics curve with a
      cutoff value of 0.5mg/dL was 0.689 (P<0.001). High serum C-reactive protein level
      (odds ratio, 2.98; confidence interval, 1.65-5.40) was independently associated
      with the 30-day rebleeding risk after adjustment for the main confounding risk
      factors, including age, blood pressure, and initial haemoglobin level.
      CONCLUSIONS: The serum C-reactive protein was an independent risk factor for 30
      day rebleeding in patients with acute nonvariceal upper gastrointestinal
      bleeding, indicating a possible role as a useful screening indicator for
      predicting the risk of rebleeding.

PMID- 25769504
TI  - Efficacy and safety of double-balloon endoscopy-assisted endoscopic papillary
      large-balloon dilatation for common bile duct stone removal.
AB  - BACKGROUND: Endoscopic retrograde cholangiopancreatography is difficult to
      perform in patients with gastrointestinal tract reconstruction. AIMS: To evaluate
      the efficacy and safety of double-balloon endoscopy-assisted endoscopic papillary
      large-balloon dilatation for common bile duct stones in patients with
      gastrointestinal tract reconstruction. METHODS: We conducted a retrospective case
      series with a comparison to historical controls. During the period 2009-2013, 11
      postoperative patients underwent endoscopic papillary large-balloon dilatation
      (Group A). Procedure efficacy and safety were compared with patients who
      underwent endoscopic sphincterotomy without endoscopic papillary large-balloon
      dilatation, who served as historical controls (Group B). RESULTS: Group A
      consisted of 11 patients (63.6% males, mean age 78+/-10 years), and Group B
      consisted of 32 patients (78.1% males, mean age 75+/-7 years). The stone
      clearance rate was significantly higher in Group A than in Group B (100% vs.
      65.6%, respectively; p<0.05). Median procedure time was significantly shorter in
      Group A than in Group B (54min vs. 102min, respectively; p<0.05), and the
      complication rate was not significantly different between groups (18% vs. 15.6%,
      respectively; p=0.586). CONCLUSION: Endoscopic papillary large-balloon dilatation
      may be an effective and safe treatment procedure in patients with
      gastrointestinal tract reconstruction.

PMID- 25769505
TI  - Endo-sponge therapy for management of anastomotic leakages after colorectal
      surgery: A case series and review of literature.
AB  - BACKGROUND: Endo-sponge treatment is a novel approach to manage selected patients
      with anastomotic leakage following colorectal surgery. However, the available
      data are still scanty. AIMS: To evaluate the efficacy and safety of the endo
      sponge therapy in a large series, and to perform a review of the current evidence
      concerning such a treatment. METHODS: Consecutive patients diagnosed with partial
      colonic anastomotic leakage managed with endo-sponge placement were enrolled. The
      endo-sponge system was changed every 48-72 h as outpatient, until to cavity
      closure. Literature review was performed for pooled-data analysis. RESULTS:
      Twenty-five patients were enrolled, including 13 (52%) with diverting ileostomy.
      Following endo-sponge applications (median sessions: 9, range: 1-39; median
      treatment duration: 4 weeks, range: 1-32), a complete healing was achieved in 22
      (88%) patients. Three (12%) patients developed a major complication (1 uretheric
      fistula, 1 ileal fistula, and 1 pararectal abscess), all successfully treated by
      surgery. Ileostomy closure was achieved in 11 (84.6%) patients. No mortality
      related to the procedure was observed. Overall, 174 patients treated with endo
      sponge were reported in literature. By considering data of the larger 7 studies,
      a complete healing of presacral cavity was achieved in 131 (94.3%) out of 149
      patients. CONCLUSIONS: Our relatively large series of patients confirmed the
      efficacy, tolerability, and an acceptably low complication rate of endo-sponge
      therapy for colorectal anastomosis leakage treatment.

PMID- 25769506
TI  - REM sleep enhancement of probabilistic classification learning is sensitive to
      subsequent interference.
AB  - During wakefulness the brain creates meaningful relationships between disparate
      stimuli in ways that escape conscious awareness. Processes active during sleep
      can strengthen these relationships, leading to more adaptive use of those stimuli
      when encountered during subsequent wake. Performance on the Weather Prediction
      Task (WPT), a well-studied measure of implicit probabilistic learning, has been
      shown to improve significantly following a night of sleep, with stronger initial
      learning predicting more nocturnal REM sleep. We investigated this relationship
      further, studying the effect on WPT performance of a daytime nap containing REM
      sleep. We also added an interference condition after the nap/wake period as an
      additional probe of memory strength. Our results show that a nap significantly
      boosts WPT performance, and that this improvement is correlated with the amount
      of REM sleep obtained during the nap. When interference training is introduced
      following the nap, however, this REM-sleep benefit vanishes. In contrast,
      following an equal period of wake, performance is both unchanged from training
      and unaffected by interference training. Thus, while the true probabilistic
      relationships between WPT stimuli are strengthened by sleep, these changes are
      selectively susceptible to the destructive effects of retroactive interference,
      at least in the short term. 

PMID- 25769507
TI  - The Association of Organizational Culture and Quality Improvement Implementation
      With Neonatal Outcomes in the NICU.
AB  - INTRODUCTION: Studies of adult patient populations suggest that organizational
      culture is associated with quality improvement (QI) implementation, as well as
      patient outcomes. However, very little research on organizational culture has
      been performed in neonatal patient populations. METHOD: This combined cross
      sectional survey and retrospective cohort study assessed employee perceptions of
      organizational culture and QI implementation within 18 Canadian neonatal
      intensive care units. The associations between these data and neonatal outcomes
      in extremely preterm infants (born at < 29 weeks' gestation) were then assessed
      using multivariable analyses. RESULTS: Perceptions of unit culture and QI
      implementation varied according to occupation and age. Higher hierarchical
      culture was associated with increased survival without major morbidities (odds
      ratio, 1.04; 95% confidence interval, 1.01-1.06), as were higher QI
      implementation scores (odds ratio range, 1.20-1.36 by culture type). DISCUSSION:
      Our data suggest that organizational culture, particularly hierarchical culture,
      and level of QI implementation may play a role in neonatal outcomes.

PMID- 25769508
TI  - Genome sequences as the type material for taxonomic descriptions of prokaryotes.
AB  - Genome sequencing of type strains promises to revolutionize prokaryotic
      systematics by greatly improving the identification of species, elucidating the
      functional properties of taxonomic groups, and resolving many of the ambiguities
      in the phylogeny of the higher taxa. Genome sequences could also serve as the
      type material for naming prokaryotic taxa, which will greatly expand the
      nomenclature governed by the Bacteriological Code to include many fastidious and
      uncultured organisms and endosymbionts of great biological interest. 

PMID- 25769509
TI  - Urban flood risk warning under rapid urbanization.
AB  - In the past decades, China has observed rapid urbanization, the nation's urban
      population reached 50% in 2000, and is still in steady increase. Rapid
      urbanization in China has an adverse impact on urban hydrological processes,
      particularly in increasing the urban flood risks and causing serious urban
      flooding losses. Urban flooding also increases health risks such as causing
      epidemic disease break out, polluting drinking water and damaging the living
      environment. In the highly urbanized area, non-engineering measurement is the
      main way for managing urban flood risk, such as flood risk warning. There is no
      mature method and pilot study for urban flood risk warning, the purpose of this
      study is to propose the urban flood risk warning method for the rapidly urbanized
      Chinese cities. This paper first presented an urban flood forecasting model,
      which produces urban flood inundation index for urban flood risk warning. The
      model has 5 modules. The drainage system and grid dividing module divides the
      whole city terrain into drainage systems according to its first-order river
      system, and delineates the drainage system into grids based on the spatial
      structure with irregular gridding technique; the precipitation assimilation
      module assimilates precipitation for every grids which is used as the model
      input, which could either be the radar based precipitation estimation or
      interpolated one from rain gauges; runoff production module classifies the
      surface into pervious and impervious surface, and employs different methods to
      calculate the runoff respectively; surface runoff routing module routes the
      surface runoff and determines the inundation index. The routing on surface grid
      is calculated according to the two dimensional shallow water unsteady flow
      algorithm, the routing on land channel and special channel is calculated
      according to the one dimensional unsteady flow algorithm. This paper then
      proposed the urban flood risk warning method that is called DPSIR model based
      multiple index fuzzy evaluation warning method, and referred to as DMFEW method.
      DMFEW first selects 5 evaluation indexes based on the DPSIR model for flood risk
      warning evaluation, including driving force index, pressure index, state index,
      impact index and response index. Based on the values of all evaluation indexes,
      one evaluation index for the whole system evaluation result is determined by
      using the fuzzy comprehensive evaluation method. The flood risk level is divided
      into 4 levels, having Level 1 the most serious. Every evaluation index is also
      categorized as 4 levels, and a linear fuzzy subjection function is proposed to do
      the fuzzy comprehensive evaluation. Dongguan City is used as the study case to
      validate the proposed method. The urban flood forecasting model is set up with
      the topographic data, the city map, the underground pipelines and land cover
      types, and two flood events are simulated with observed precipitation, one is
      interpolated from the rain gauges data, and another is estimated by digital
      weather radar. The simulated results are compared with the investigated water
      depth, and the results show the model has very good performances. The results are
      further used for the flood risk warning simulation, and are very reasonable.

PMID- 25769510
TI  - Hands-on defibrillation: "Gloves as sweet as damask roses" (William Shakespeare:
      The winter's tale).

PMID- 25769511
TI  - An observational near-infrared spectroscopy study on cerebral autoregulation in
      post-cardiac arrest patients: time to drop 'one-size-fits-all' hemodynamic
      targets?
AB  - AIMS: A subgroup of patients with ROSC after cardiac arrest (CA) with disturbed
      cerebral autoregulation might benefit from higher mean arterial pressures (MAP).
      We aimed to (1) phenotype patients with disturbed autoregulation, (2) investigate
      whether these patients have a worse prognosis, (3) define an individual optimal
      MAP per patient and (4) investigate whether time under this individual optimal
      MAP is associated with outcome. METHODS: Prospective observational study in 51
      post-CA patients monitored with near infrared spectroscopy. RESULTS: (1) 18/51
      patients (35%) had disturbed autoregulation. Phenotypically, a higher proportion
      of patients with disturbed autoregulation had pre-CA hypertension (31+/-47 vs.
      65+/-49%, p=0.02) suggesting that right shifting of autoregulation is caused by
      chronic adaptation of cerebral blood flow to higher blood pressures. (2) In
      multivariate analysis, patients with preserved autoregulation (n=33, 65%) had a
      significant higher 180-days survival rate (OR 4.62, 95% CI [1.06:20.06], p=0.04].
      Based on an index of autoregulation (COX), the average COX-predicted optimal MAP
      was 85 mmHg in patients with preserved and 100 mmHg in patients with disturbed
      autoregulation. (3) An individual optimal MAP could be determined in 33/51
      patients. (4) The time under the individual optimal MAP was negatively associated
      with survival (OR 0.97, 95% CI [0.96:0.99], p=0.02). The time under previously
      proposed fixed targets (65, 70, 75, 80 mmHg) was not associated with a
      differential survival rate. CONCLUSION: Cerebral autoregulation showed to be
      disturbed in 35% of post-CA patients of which a majority had pre-CA hypertension.
      Disturbed cerebral autoregulation within the first 24h after CA is associated
      with a worse outcome. In contrast to uniform MAP goals, the time spent under a
      patient tailored optimal MAP, based on an index of autoregulation, was negatively
      associated with survival.

PMID- 25769512
TI  - Feasibility and clinical efficacy of left atrial ablation for the treatment of
      atrial tachyarrhythmias in patients with left atrial appendage closure devices.
AB  - BACKGROUND: Left atrial appendage (LAA) closure devices have been introduced
      recently as an alternative for oral anticoagulation (OAC) in patients with
      nonvalvular atrial fibrillation (AF). Because of potential overlap of ablation
      target areas and the previously implanted LAA closure device, as well as
      potential complications such as mechanical damage to the device, left atrial (LA)
      ablation remains a subject of debate in these patients. OBJECTIVE: We report on
      the feasibility and clinical efficacy of LA ablation after implantation of LAA
      closure devices. METHODS: Eight patients (6 men; age 69 +/- 8 years) with
      symptomatic paroxysmal AF (n = 5) or persistent AF (mean CHA2DS2-VASc score 3.6
      +/- 0.7, mean HAS-BLED score 3.6 +/- 1.5) and previously implanted WATCHMAN (7
      patients) or AMPLATZER Cardiac Plug (1 patient) LAA closure devices received
      radiofrequency-based LA ablation (4 via circumferential pulmonary vein isolation
      [CPVI], 4 via CPVI and additional LA linear lesions or complex fractionated
      atrial electrograms) after a mean of 201 days (range 41-756 days) after LAA
      closure. RESULTS: Successful LA ablation was achieved without device interference
      or periprocedural complications. After a mean of 503 days (range 113-1006 days),
      transesophageal echocardiography (TEE) was performed in all patients to assess
      for device-related complications. No device dislocation or leakage was observed.
      In 1 patient (12.5%), a device-related thrombus was found despite therapeutic OAC
      with dabigatran. Five patients (63%) remained in stable sinus rhythm, and no
      bleeding events or stroke occurred during a follow-up of 554 days (range 218-1006
      days). CONCLUSION: LA ablation after LAA closure appears to be feasible. Device
      related thrombus formation in 1 patient suggests the need for further TEE
      examinations after LA ablation after LAA closure device implantation.

PMID- 25769513
TI  - Quantitative histopathology of the Mediterranean mussel (Mytilus
      galloprovincialis L.) exposed to the harmful dinoflagellate Ostreopsis cf. ovata.
AB  - Ostreopsis cf. ovata is a benthic dinoflagellate that produces palytoxin-like
      compounds that adversely affect both marine vertebrates and invertebrates and are
      reported to be responsible for human intoxication in aerosol form. In this work,
      a histopathological analysis accompanied by quantitative evaluation of tissue
      injury in mussels (Mytilus galloprovincialis) exposed to O. cf. ovata cells under
      natural and experimental conditions, provided baseline data on the health status
      of the mussels in terms of defensive and regressive pathological changes. We
      recorded a total of 15 health parameters in the digestive system, muscle, kidney
      and gills in mussels exposed to O. cf. ovata both in the laboratory and at sea.
      Animals exposed to different concentrations of O. cf. ovata cells (300, 500 and
      1000cellsml(-)(1)) for 48h showed activation of the inflammatory response, which
      increased with the cell concentration, mainly characterized by haemocyte
      aggregates actively enclosing the algae, while mussel mortality was also recorded
      in some cases. Moreover the use of image analysis for the evaluation of digestive
      tubule damage revealed a pronounced increase in the lumen in terms of its area,
      perimeter and circularity, with a shift in a high percentage of tubules from an
      adsorbing profile to an atrophic profile. Animals collected from the natural
      environment during a summer bloom of O. cf. ovata in the Gulf of Naples (Italy)
      showed comparable lesions in terms of types and severity. This is the first
      quantitative study assessing damage to the digestive epithelia in terms of lumen
      modifications in mussels exposed to O. cf. ovata. The presented methodology
      provides a new technique for automating the evaluation of epithelial tubule
      modifications. Our results highlight the importance of monitoring the presence of
      O. cf. ovata in this area, taking into account the effects on the residing marine
      species. 

PMID- 25769514
TI  - Variations in prevalence of viral, bacterial, and rhizocephalan diseases and
      parasites of the blue crab (Callinectes sapidus).
AB  - Prevalence of blue crab diseases and parasites has not been consistently
      monitored in the Gulf of Mexico. To establish current prevalence levels and to
      more fully understand population dynamics, commercial landing trends, and effects
      of future natural and anthropogenic disasters on animal health, we measured the
      prevalence of white spot syndrome virus (WSSV), Loxothylacus texanus, shell
      disease, and Vibrio spp. in blue crabs collected from Louisiana in 2013 and the
      beginning of 2014. We used PCR to detect WSSV and L. texanus infections, visual
      gross diagnosis for L. texanus externae and shell disease, and standard
      microbiological culture techniques and biochemical testing for Vibrio spp. We
      found no crabs infected with WSSV or L. texanus. Absence of L. texanus
      parasitization was expected based on the sampled salinities and the sampling
      focus on large crabs. Shell disease was present at a level of 54.8% and was most
      prevalent in the winter and summer and least prevalent in the spring. Vibrio spp.
      were found in the hemolymph of 22.3% of the crabs and prevalence varied by site,
      season, and sex. Additionally, three of 39 crabs tested were infected with reo
      like virus. 

PMID- 25769515
TI  - Nuclear quantum effects and kinetic isotope effects in enzyme reactions.
AB  - Enzymes are extraordinarily effective catalysts evolved to perform well-defined
      and highly specific chemical transformations. Studying the nature of rate
      enhancements and the mechanistic strategies in enzymes is very important, both
      from a basic scientific point of view, as well as in order to improve rational
      design of biomimetics. Kinetic isotope effect (KIE) is a very important tool in
      the study of chemical reactions and has been used extensively in the field of
      enzymology. Theoretically, the prediction of KIEs in condensed phase environments
      such as enzymes is challenging due to the need to include nuclear quantum effects
      (NQEs). Herein we describe recent progress in our group in the development of
      multi-scale simulation methods for the calculation of NQEs and accurate
      computation of KIEs. We also describe their application to several enzyme
      systems. In particular we describe the use of combined quantum
      mechanics/molecular mechanics (QM/MM) methods in classical and quantum
      simulations. The development of various novel path-integral methods is reviewed.
      These methods are tailor suited to enzyme systems, where only a few degrees of
      freedom involved in the chemistry need to be quantized. The application of the
      hybrid QM/MM quantum-classical simulation approach to three case studies is
      presented. The first case involves the proton transfer in alanine racemase. The
      second case presented involves orotidine 5'-monophosphate decarboxylase where
      multidimensional free energy simulations together with kinetic isotope effects
      are combined in the study of the reaction mechanism. Finally, we discuss the
      proton transfer in nitroalkane oxidase, where the enzyme employs tunneling as a
      catalytic fine-tuning tool. 

PMID- 25769516
TI  - Health at Every Size College Course Reduces Dieting Behaviors and Improves
      Intuitive Eating, Body Esteem, and Anti-Fat Attitudes.
AB  - OBJECTIVE: To investigate the effects of a Health at Every Size general education
      course on intuitive eating, body esteem (BES), cognitive behavioral dieting
      scores, and anti-fat attitudes of college students. METHODS: Quasi-experimental
      design with 149 students in intervention (45), comparison (66), or control (46)
      groups. Analysis of variance and post hoc Tukey adjusted tests were used.
      RESULTS: Mean scores for total general education course on intuitive eating (P <
      .001), unconditional permission to eat (P < .001), reliance on hunger (P < .001),
      cognitive behavioral dieting scores (P < .001), BES appearance (P = .006), BES
      weight (P < .001), and anti-fat attitudes (P < .001) significantly improved from
      pre to post in the intervention group compared with control and comparison
      groups. CONCLUSION AND IMPLICATIONS: Students in the Health at Every Size class
      improved intuitive eating, body esteem, and anti-fat attitudes and reduced
      dieting behaviors compared with students in the control and comparison groups.

PMID- 25769517
TI  - beta-sheet interfering molecules acting against beta-amyloid aggregation and
      fibrillogenesis.
AB  - beta-Sheet aggregates and amyloid fibrils rising from conformational changes of
      proteins are observed in several pathological human conditions. These structures
      are organized in beta-strands that can reciprocally interact by hydrophobic and
      pi-pi interactions. The amyloid aggregates can give rise to pathological
      conditions through complex biochemical mechanisms whose physico-chemical nature
      has been understood in recent times. This review focuses on the various classes
      of natural and synthetic small molecules able to act against beta-amyloid
      fibrillogenesis and toxicity that may represent new pharmacological tools in
      Alzheimer's diseases. Some peptides, named 'beta-sheet breaker peptides', are
      able to hamper amyloid aggregation and fibrillogenesis by interfering with and
      destabilizing the non native beta-sheet structures. Other natural compounds, like
      polyphenols or indolic molecules such as melatonin, can interfere with beta
      amyloid peptide pathogenicity by inhibiting aggregation and counteracting
      oxidative stress that is a key hallmark in Alzheimer's disease. 

PMID- 25769518
TI  - Development of a time-resolved fluorescence probe for evaluation of competitive
      binding to the cholecystokinin 2 receptor.
AB  - The synthesis, characterization, and use of Eu-DTPA-PEGO-Trp-Nle-Asp-Phe-NH2 (Eu
      DTPA-PEGO-CCK4), a luminescent probe targeted to cholecystokinin 2 receptor
      (CCK2R, aka CCKBR), are described. The probe was prepared by solid phase
      synthesis. A Kd value of 17+/-2nM was determined by means of saturation binding
      assays using HEK-293 cells that overexpress CCK2R. The probe was then used in
      competitive binding assays against Ac-CCK4 and three new trivalent CCK4
      compounds. Repeatable and reproducible binding assay results were obtained. Given
      its ease of synthesis, purification, receptor binding properties, and utility in
      competitive binding assays, Eu-DTPA-PEGO-CCK4 could become a standard tool for
      high-throughput screening of compounds in development targeted to cholecystokinin
      receptors. 

PMID- 25769519
TI  - Molecular design of Cy3 derivative for highly sensitive in-stem molecular beacon
      and its application to the wash-free FISH.
AB  - We herein describe a novel in-stem molecular beacon (ISMB) containing multiple
      Cy3-quencher pairs on d-threoninol scaffolds in the stem region. The designed Cy3
      derivative was not significantly quenched by the adjacent nucleobases, self
      quenching of the fluorophore was minimal, and the fluorophore did not severely
      destabilize the duplex. Using newly designed Cy3, we synthesized ISMBs containing
      two Cy3 moieties. The signal to background ratio of the ISMB containing two Cy3
      moieties was above 100, whereas that with one Cy3 was 30. A Cy3-derivative
      containing ISMB used in a fluorescence in situ hybridization (FISH) detected
      endogenous beta-actin mRNA in fixed cells without need for washing procedures. 

PMID- 25769520
TI  - The association between alexithymia as assessed by the 20-item Toronto
      Alexithymia Scale and depression: A meta-analysis.
AB  - Patients with depression exhibit high rates of alexithymia, representing a major
      public health concern. We sought to examine relationships between depression
      severity and alexithymia as assessed by the Toronto Alexithymia Scale (TAS-20)
      and the TAS-20 subscales of difficulty identifying feelings (DIF), difficulty
      describing feelings (DDF), and externally oriented thinking (EOT). Potentially
      relevant studies were obtained independently by two reviewers. Chi-square
      statistics based on the Q-test and I(2) index assessed statistical heterogeneity
      between studies. Subgroup analyses were mainly used to explore sources of
      heterogeneity. Begg's test and Duval and Tweedie' trim and fill were used to
      assess potential publication bias. Altogether, 3572 subjects from 20 study groups
      across 19 studies were included. Medium relationships were observed between
      depression and TAS-total score (TAS-TS), DIF, and DDF. There was also a weak
      relationship between EOT and depression. Subgroup analyses showed a stronger
      correlation between TAS-TS and depression assessed by self-reported tools than
      that assessed by the Hamilton Rating Scale for Depression. The heterogeneity
      significantly decreased only in the subgroup analysis by depression tool. We
      conclude that alexithymia, as assessed by the TAS-20 and its subscales DIF and
      DDF, is closely related to depression. These relationships were affected by
      depression measurement tools. 

PMID- 25769521
TI  - The place of and evidence for serotonin reuptake inhibitors (SRIs) for obsessive
      compulsive disorder (OCD) in children and adolescents: Views based on a
      systematic review and meta-analysis.
AB  - Serotonin reuptake inhibiting drugs (SRI) have been used in the treatment of
      paediatric obsessive-compulsive disorder over the past 30 years. We performed a
      systematic review and meta-analysis of the literature to discuss the place of and
      evidence for the use of SRI in paediatric OCD, based on 14 publications of
      methodologically sound, randomized and controlled studies. Both SRI and specific
      SRIs were examined and comparisons of SRI, placebo, cognitive behaviour therapy
      (CBT), combined (COMBO) treatments (SRI+CBT) made to investigate their relative
      efficacy. Using the Cochrane methodology, and as measures of effect size mean
      difference and Hedge's g, SRIs proved to be superior to drug placebo, with a
      modest effect size. From direct comparisons of CBT and SRI treatments, we
      conclude that CBT has the superior efficacy. COMBO versus CBT shows that SRI
      treatment adds little to concomitant CBT, while COMBO shows favourable outcome
      versus SRI alone. In pre-trial partial treatment responders, those who failed a
      SRI had better outcome from adding CBT as compared to continuing a SRI. Those who
      failed CBT treatment did as well with continued CBT as with switching to a SRI.
      The studies of combinations and sequences of treatments need to be developed
      further. 

PMID- 25769522
TI  - New organic nitrate-containing benzyloxy isonipecotanilide derivatives with
      vasodilatory and anti-platelet activity.
AB  - A number of new nitric oxide (NO)-precursors were synthesized by grafting nitrate
      containing moieties on the structures of the benzyloxy isonipecotanilide
      derivatives 1 and 2 already reported as moderately potent antiplatelet agents.
      Various nitrooxy (ONO2)-alkyl side chains were covalently linked to the
      piperidine nitrogen of the parent compounds through carbamate and amide linkage,
      and the synthesis of a benzyl nitrate analog (15) of compound 1 was also
      achieved. The in vitro vasodilatory activities, as well as platelet anti
      aggregatory effects, of the newly synthesized organic nitrates were assessed. The
      (ONO2)methyl carbamate-based derivative 5a and the benzyl nitrate analog 15,
      which on the other hand retain activity as inhibitors of ADP-induced platelet
      aggregation, exhibited strong NO-mediated vasodilatory effects on pre-contracted
      rat aorta strips, with EC50 values in the low nanomolar range (13 and 29 nM,
      respectively). Experiments carried out with the selectively inhibited soluble
      guanylate cyclase (sGC), which is the key enzyme of the NO-mediated pathway
      leading to vascular smooth muscle relaxation, confirmed the involvement of NO in
      the observed vasodilation. The nitrate derivatives proved to be stable in acidic
      aqueous solution and at pH 7.4. In human serum, unlike 5a, which showed not to
      undergo enzyme-catalyzed decomposition, the other tested (ONO2)-alkyl carbamate
      based compounds (5b and 5e) and benzyl nitrate 15 underwent a faster degradation.
      However, their decomposition rates in serum were quite slow (t1/2>2.6 h), which
      suggests that nitrate moiety is poorly metabolized in blood plasma and that much
      of the in vitro anti-platelet activity has to be attributed to the intact (ONO2)
      containing molecules.

PMID- 25769523
TI  - Enhanced hepatic targeting, biodistribution and antifibrotic efficacy of
      tanshinone IIA loaded globin nanoparticles.
AB  - Tanshinone IIA (TA) has been recently used to treat liver diseases. However, the
      poor water solubility and fast metabolism obstruct TA in to be used for the
      treatment of liver diseases. To overcome this, TA was encapsulated into globin to
      form nanoparticles (TA-Gb-NPs) by our self-assembling method. We evaluated their
      biodistribution, pharmacokinetics, targeting ability to liver and antifibrotic
      effects. As a result, TA-Gb-NPs had a good hepatic targeting ability and achieved
      higher concentration and longer retention in liver than tanshinone IIA suspension
      (TA-S). Compared with TA-S, TA-Gb-NPs significantly improved serum biochemical
      parameters in thioacetamide (TAA) induced liver fibrosis mouse model.
      Furthermore, histological analysis of mouse liver slices revealed that TA-Gb-NPs
      could markedly reduce the fibrosis scores and attenuate the progression of the
      hepatic fibrosis. In conclusion, the TA-Gb-NPs may be a good candidate for the
      treatment of hepatic fibrosis. 

PMID- 25769524
TI  - Identification of potential Mycobacterium tuberculosis topoisomerase I
      inhibitors: a study against active, dormant and resistant tuberculosis.
AB  - Mycobacterium tuberculosis (Mtb) topoisomerase I (Topo I), involved in the
      relaxation of negatively supercoiled DNA, plays an important role in the
      viability of pathogen Mtb. Being one of the most significant enzymes; it also
      takes part in crucial biological pathways such as transcription and replication
      of the pathogen. The present study aims at the development of Mtb Topo I 3D
      protein structure which in turn was employed for the virtual screening of
      compound libraries in a process of identification of a hit molecule. The
      identified hit, hydroxycamptothecin, was active at 6.25 MUM which was further
      derivatized synthetically into fifteen novel analogues. Among these, four
      compounds (3b, 3g, 3h and 3l) emerged to be active displaying IC50 values ranging
      from 2.9 to 9.3 MUM against Mtb Topo I and were non-cytotoxic at 25 MUM. These
      four compounds also proved their efficacy when tested against active, dormant and
      resistant forms of Mtb. The most potent inhibitor 3b was screened for in vivo
      anti-mycobacterial activity using zebrafish model and was found to be more
      effective when compared to first line anti-tubercular drugs, isoniazid and
      rifampicin. The binding affinity of this compound towards Mtb Topo I was analyzed
      by differential scanning fluorimetry which resulted in a positive shift in
      melting temperature when compared to the native protein thereby proving its
      stabilization effect over protein.

PMID- 25769525
TI  - Analysis of small intestinal transit and colon arrival times of non
      disintegrating tablets administered in the fasted state.
AB  - In this study individual data on tablet gastrointestinal transit times (i.e.
      gastric emptying, small intestinal transit, ileocecal junction residence, and
      colon arrival times) were obtained from literature in order to present and
      analyze their distributions and relationships. The influence of the time of food
      intake after tablet administration in fasted state on gastrointestinal transit
      times was additionally evaluated. There were 114 measurements from subjects who
      received the first meal at 4h after tablet administration. Approximately 32% of
      the tablets arrived into the colon before the meal intake at 4h. An evident
      increase in the frequency of colon arrival of tablets within 40min after the meal
      intake at 4h post-dose was observed, where approximately 39% of all tablets
      arrived into the colon. This is in accordance with findings described in
      literature where a meal ingested several hours post-dose accelerates tablet
      transit through the terminal ileum and shortens the transit through the small
      intestine. The median (min, max) of gastric emptying, small intestinal transit,
      and colon arrival times in the group where the first meal intake was at 4h post
      dose is 35 (0,192), 215 (60,544), and 254 (117,604) minutes, respectively. The
      dependence of colon arrival times on gastric emptying times was described by the
      nonparametric regression curve, and compared with the presumed interval of colon
      arrival times, calculated by summation of observed gastric emptying times and
      frequently cited small intestinal transit time interval, i.e. 3-4h. For shorter
      gastric emptying times the trend of colon arrival times was within the presumed
      interval. At short gastric emptying times many observation points are also within
      the presumed interval since this interval coincides with short period after meal
      intake at 4h post-dose. Additionally, in numerous occasions relatively long
      ileocecal junction residence times were obtained, which may be important
      information from the point of view of drug absorption. The findings of
      gastrointestinal transit times are important and should be taken into
      consideration when predicting the in vivo performance of dosage forms after oral
      administration. 

PMID- 25769526
TI  - Urinary tract infections due to extended-spectrum beta-lactamase-producing Gram
      negative bacteria: identification of risk factors and outcome predictors in an
      Australian tertiary referral hospital.
AB  - OBJECTIVES: Extended-spectrum beta-lactamase-expressing Gram-negative bacilli
      (ESBL-GNB) now commonly cause community-acquired infections, including urinary
      tract infections (UTI), and represent a challenge for practitioners in choosing
      empirical antibiotics. The aim of this study was to describe the epidemiology and
      clinical characteristics of UTIs/bacteriuria due to ESBL-GNB in Australia.
      METHODS: At a single-site tertiary referral hospital, 100 cases with
      UTIs/bacteriuria due to ESBL-GNB were matched to 100 cases where UTIs/bacteriuria
      were caused by organisms matching the ESBL bacterial species that had routine
      susceptibility to antibiotics. Potential risk factors for ESBL-GNB
      UTI/bacteriuria and differences in clinical outcomes were identified. RESULTS:
      Length of admission prior to positive sample (odds ratio (OR) 1.3, p = 0.03, per
      week), exposure to antibiotics (OR 5.7, p < 0.001), return from overseas travel
      (OR 6.5, p = 0.002), and nursing home residency (OR 4.2, p = 0.03) were
      identified as risk factors associated with ESBL-GNB UTI/bacteriuria in the
      multivariate analysis. In addition, ESBL-GNB-infected cases subsequently had a
      longer inpatient stay (median 6 vs. 2 days, p = 0.002) and were admitted to the
      intensive care unit more frequently (28/100 vs. 8/100, p < 0.001). CONCLUSIONS:
      Our results emphasize the need for culture of a mid-stream urine specimen prior
      to commencing antibacterials, especially in patients with the risk factors
      identified herein associated with ESBL-GNB UTI/bacteriuria.

PMID- 25769528
TI  - DNA cleavage by CgII and NgoAVII requires interaction between N- and R-proteins
      and extensive nucleotide hydrolysis.

PMID- 25769529
TI  - Evaluation of an immunochromatographic assay for detection of PBP2a on non
      Staphylococcus aureus clinical isolates.
AB  - We evaluated the immunochromatographic assay PBP2a Culture Colony Test (AlereTM)
      on 50 samples of methicillin resistant and sensitive non-Staphylococcus aureus
      isolates belonging to ten species. Because it is rapid and reliable, this test
      should be advantageous as routine test in place of mecA/C PCR. 

PMID- 25769527
TI  - Deacetylase inhibitors repress STAT5-mediated transcription by interfering with
      bromodomain and extra-terminal (BET) protein function.
AB  - Signal transducer and activator of transcription STAT5 is essential for the
      regulation of proliferation and survival genes. Its activity is tightly regulated
      through cytokine signaling and is often upregulated in cancer. We showed
      previously that the deacetylase inhibitor trichostatin A (TSA) inhibits STAT5
      mediated transcription by preventing recruitment of the transcriptional machinery
      at a step following STAT5 binding to DNA. The mechanism and factors involved in
      this inhibition remain unknown. We now show that deacetylase inhibitors do not
      target STAT5 acetylation, as we initially hypothesized. Instead, they induce a
      rapid increase in global histone acetylation apparently resulting in the
      delocalization of the bromodomain and extra-terminal (BET) protein Brd2 and of
      the Brd2-associated factor TBP to hyperacetylated chromatin. Treatment with the
      BET inhibitor (+)-JQ1 inhibited expression of STAT5 target genes, supporting a
      role of BET proteins in the regulation of STAT5 activity. Accordingly, chromatin
      immunoprecipitation demonstrated that Brd2 is associated with the
      transcriptionally active STAT5 target gene Cis and is displaced upon TSA
      treatment. Our data therefore indicate that Brd2 is required for the proper
      recruitment of the transcriptional machinery at STAT5 target genes and that
      deacetylase inhibitors suppress STAT5-mediated transcription by interfering with
      Brd2 function. 

PMID- 25769530
TI  - Detailed search for protein kinase(s) involved in plasma membrane H+-ATPase
      activity regulation of yeast cells.
AB  - This study displays a screening using yeast strains deficient in protein kinases
      known to exist in Saccharomyces cerevisiae. From 95 viable single mutants, 20
      mutants appear to be affected in the glucose-induced extracellular acidification.
      The mutants that are unaffected in calcium signaling were tested for their
      sensitivity to hygromycin B. Furthermore, we verified whether the remaining
      mutants produced enzymes that are appropriately incorporated at plasma membrane.
      Finally, we measure the kinetic properties of the enzyme in purified plasma
      membranes from glucose-starved as well as glucose-fermenting cells. We confirmed
      the kinase Ptk2 involvement in H(+)-ATPase regulation (increase of affinity for
      ATP). However, the identification of the kinase(s) responsible for
      phosphorylation that leads to an increase in Vmax appears to be more complex.
      Complementary experiments were performed to check how those protein kinases could
      be related to the control of the plasma membrane H(+)-ATPase and/or the potential
      membrane. In summary, our results did not permit us to identify the protein
      kinase(s) involved in regulating the catalytic efficiency of the plasma membrane
      H(+)-ATPase. Therefore, our results indicate that the current regulatory model
      based on the phosphorylation of two different sites located in the C-terminus
      tail of the enzyme could be inappropriate. 

PMID- 25769531
TI  - Familial Hypercholesterolemia: a Review of the Natural History, Diagnosis, and
      Management.
AB  - Familial hypercholesterolemia (FH) is an inherited disorder of lipid metabolism
      characterized by premature cardiovascular disease. It is one of the most common
      metabolic disorders affecting humans. There are two clinical manifestations: the
      milder heterozygous form and more severe homozygous form. Despite posing a
      significant health risk, FH is inadequately diagnosed and managed. As the
      clinical outcome is related to the degree and duration of exposure to elevated
      low-density lipoprotein cholesterol (LDL-C) levels, early treatment is vital.
      Diagnosis can usually be made using a combination of clinical characteristics
      such as family history, lipid levels, and genetic testing. Mutations in the gene
      encoding the LDL receptor (LDLR), apolipoprotein B, the pro-protein convertase
      subtilisin/kexin 9 (PCSK9), and LDLR adaptor protein are the commonest
      abnormalities. Early identification and treatment of patients, as well as
      screening of relatives, helps significantly reduce the risk of premature disease.
      Although statins remain the first-line therapy in most cases, monotherapy is
      usually inadequate to control elevated LDL-C levels. Additional therapy with
      ezetimibe and bile acid sequestrants may be required. Newer classes of
      pharmacotherapy currently under investigation include lomitapide, mipomersen, and
      monoclonal antibodies to PCSK9. Lipoprotein apheresis may be required when
      multiple pharmacotherapies are inadequate, especially in the homozygous form.
      Effective early detection and treatment of the index individual and initiation of
      cascade screening will help reduce the complications associated with FH. In this
      article, we review the disease of FH, complexity of diagnosis and management, and
      the challenges faced in preventing the significant morbidity and mortality
      associated with it. 

PMID- 25769533
TI  - Abstracts of the 62nd Annual Scientific Meeting, March 26-28, 2015, San
      Francisco, California.

PMID- 25769534
TI  - Publication rates of podium versus poster presentations at the American
      Orthopaedic Society for Sports Medicine meetings: 2006-2010.
AB  - BACKGROUND: Presentations at scientific meetings are often used to influence
      clinical practice, yet many presentations are not ultimately published in peer
      reviewed journals. Previously reported publication rates for orthopaedic
      specialties have varied from 34% to 52%. In addition, the publication rate of
      accepted abstracts is a strong indicator of meeting quality, and it has a
      potential effect on clinical practice. To date, no studies have investigated
      publication rates in the field of sports medicine, and specifically for abstracts
      presented at American Orthopaedic Society for Sports Medicine (AOSSM) meetings.
      PURPOSE: To determine the overall publication rate of abstracts presented at
      AOSSM annual meetings and whether there were differences in publication rates
      between poster and podium presentations. STUDY DESIGN: Descriptive epidemiology
      study. METHODS: A comprehensive search was performed using PubMed and Google
      Scholar for all published manuscripts pertaining to abstracts presented at the
      2006 to 2010 AOSSM annual meetings. Abstracts were classified according to
      presentation type (podium, poster) and subsequently were categorized into
      subspecialty area and study design. For published abstracts, the journal and
      publication date were recorded. RESULTS: A total of 1665 abstracts were submitted
      to AOSSM annual meetings from 2006 to 2010, with 444 abstracts accepted (26.7%
      overall acceptance rate); there were 277 podium presentations and 167 posters. Of
      these 444 abstracts, 298 (67.1%) were published within 3 years in peer-reviewed
      journals. The overall publication rates for podium and poster presentations were
      73.3% and 56.9%, respectively. For the combined years of 2006 to 2010, podium
      presentations were 2.08 (95% CI, 1.39-3.11) times more likely to be published
      compared with poster presentations. CONCLUSION: The overall publication rate of
      abstracts presented at AOSSM annual meetings (67.1%) was much higher than that
      reported for other orthopaedic meetings (34%-52%), highlighting the overall
      educational value and information quality of AOSSM meetings. In addition, there
      was a significant difference in the overall publication rates for podium and
      poster presentations. These data suggest that the quality and type of poster and
      podium presentations may not be equal, and these potential differences should be
      kept in mind when considering changes in clinical practice according to type of
      meeting presentation. Furthermore, AOSSM annual meeting program planners should
      consider these results when investigating ways to further improve the quality of
      research presented.

PMID- 25769535
TI  - Arthroscopy skills development with a surgical simulator: a comparative study in
      orthopaedic surgery residents.
AB  - BACKGROUND: Surgical simulation has become increasingly relevant to orthopaedic
      surgery education and could translate to improved operating room proficiency in
      orthopaedic surgery trainees. PURPOSE: To compare the arthroscopic performance of
      junior orthopaedic surgery residents who received training with a knee and
      shoulder arthroscopy surgical simulator with those who received didactic
      training. STUDY DESIGN: Controlled laboratory study. METHODS: Fourteen junior
      orthopaedic surgery residents at a single institution were randomized to receive
      knee and shoulder arthroscopy training with a surgical simulator (n = 8) or
      didactic lectures with arthroscopy models (n = 6). After their respective
      training, performance in diagnostic knee and shoulder arthroscopy was assessed
      using a cadaveric model. Time to completion and assessment of arthroscopic
      handling using a subjective injury grading index (scale, 1-10) was then used to
      evaluate performance in final cadaveric testing. RESULTS: Orthopaedic surgery
      residents who trained with a surgical simulator outperformed the didactic-trained
      residents in shoulder arthroscopy by time to completion (-35%; P = .02) and
      injury grading index (-35%; P = .01). In addition, a trend toward improved
      performance of knee arthroscopy by the simulator-trained group was found by time
      to completion (-36%; P = .09) and injury grading index (P = .08). CONCLUSION: In
      this study, junior orthopaedic surgery residents who trained with a surgical
      simulator demonstrated improved arthroscopic performance in both knee and
      shoulder arthroscopy. However, future validation of surgical simulator training
      for orthopaedic surgery residents remains warranted. CLINICAL RELEVANCE: Surgical
      skill development with an arthroscopy surgical simulator could translate to
      improved arthroscopy performance in the operating room.

PMID- 25769536
TI  - Inoculation with nitrogen turnover bacterial agent appropriately increasing
      nitrogen and promoting maturity in pig manure composting.
AB  - The nitrogen turnover bacterial (NTB) agent, which is closely related to nitrogen
      turnover, was comprised of a bacterial consortium of ammonifiers, nitrobacteria
      and Azotobacter in this study. The three constituents of the bacterial consortium
      were added to pig manure and wheat straw mixtures in different doses and at
      different times, and subsequently composted to investigate their effects on
      nitrogen transformation and maturity. Throughout the period, the total N loss was
      35-56%, 10.7-22.7% of which consisted of NH3, and 18-35% of the initial organic
      carbon was degraded. Adding the NTB agent prolonged the thermophilic stage by one
      to six days compared to the control. The lowest N loss (35%), the highest
      degradation rate of organic carbon (35%) and the greatest increase in total
      nitrogen content (36.1%) occurred in the inoculation with 1% NTB agent at the
      beginning of composting. However, adding 1% NTB agent after the thermophilic
      stage and 3% NTB agent at the beginning of composting had no positive effect with
      respect to retaining nitrogen or accelerating the maturation process. Therefore,
      the inoculation with 1% NTB agent at the beginning of composting was effective
      for reducing N loss and promoting maturity. 

PMID- 25769537
TI  - Identification of influencing municipal characteristics regarding household waste
      generation and their forecasting ability in Biscay.
AB  - The planning of waste management strategies needs tools to support decisions at
      all stages of the process. Accurate quantification of the waste to be generated
      is essential for both the daily management (short-term) and proper design of
      facilities (long-term). Designing without rigorous knowledge may have serious
      economic and environmental consequences. The present works aims at identifying
      relevant socio-economic features of municipalities regarding Household Waste (HW)
      generation by means of factor models. Factor models face two main drawbacks, data
      collection and identifying relevant explanatory variables within a heterogeneous
      group. Grouping similar characteristics observations within a group may favour
      the deduction of more robust models. The methodology followed has been tested
      with Biscay Province because it stands out for having very different
      municipalities ranging from very rural to urban ones. Two main models are
      developed, one for the overall province and a second one after clustering the
      municipalities. The results prove that relating municipalities with specific
      characteristics, improves the results in a very heterogeneous situation. The
      methodology has identified urban morphology, tourism activity, level of education
      and economic situation as the most influencing characteristics in HW generation. 

PMID- 25769538
TI  - Some popular medicinal plants and diseases of the Upper Palaeolithic in Western
      Georgia.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Palynological studies of cultural layers of cave
      sediments have been used in order to better understand traditional practices. The
      Upper Palaeolithic in Georgia (36,000-11,000 cal. BP) provides a rich source of
      such material. However, up to day from such sediments the identification of
      medicinal plants has hardly been achieved. Large quantities of pollen most
      notably from entomophilous taxa in fossil spectra can serve as a tool to identify
      traditionally important species. As these plants are used in modern popular
      medicine on the territory of Georgia (like Achillea millefolium L., Artemisia
      annua L., Artemisia absinthium L., Centaurea jacea L., Urtica dioica L.) can be
      served as an indirect evidence for their medicinal relevance from the
      Palaeolithic Period up to days. Their modern uses may point that the main
      diseases during the Upper Palaeolithic were the same as today. MATERIALS AND
      METHODS: The Upper Palaeolithic sediments were studied palynologically come from
      four caves: Dzudzuana, Satsurblia, Kotias Klde and Bondi. Modern sediments were
      investigated from 6 caves. Fossil and modern samples were taken according to the
      standard procedure in palynology. The laboratory treatment was carried out as
      follows: first, 50g of the sample was boiled in 10% KOH. At the second stage,
      centrifuging of the material in cadmium liquid was performed. At the final stage,
      acetolysis treatment was used. RESULTS: Pollen of A. absinthium L. (Asteraceae),
      A. annua L. (Asteraceae), A. millefolium L. (Asteraceae), C. jacea L.
      (Asteraceae), and U. dioica L. (Urticaceae) are identified to species level. This
      species are not edible and are popular in present-day folk medicine. In the Upper
      Palaeolithic layers, significant amounts of studies species pollen were recorded
      in the cave, likely due to their flowering branches being brought in by humans
      for use. Detailed consideration of the pharmacological characteristics of the
      examined species showed that almost all of them have anti-inflammatory,
      antibacterial, antimicrobial and antipyretic activity. CONCLUSION: The fossil
      pollen complex of medicinal herbs, dominated by A. millefolium and Artemisia (A.
      annua and A. absinthium), suggests that the ancient population living in the
      studied caves could have been prone to malaria, rheumatism and gastrointestinal
      diseases. In the Upper Palaeolithic, the population inhabiting cave sites might
      have suffered from gout and callouses.

PMID- 25769539
TI  - Ofatumumab monotherapy in fludarabine-refractory chronic lymphocytic leukemia:
      final results from a pivotal study.

PMID- 25769540
TI  - Combined immunodeficiency with CD4 lymphopenia and sclerosing cholangitis caused
      by a novel loss-of-function mutation affecting IL21R.

PMID- 25769541
TI  - Health-related quality-of-life in patients with newly diagnosed multiple myeloma
      in the FIRST trial: lenalidomide plus low-dose dexamethasone versus melphalan,
      prednisone, thalidomide.
AB  - We compared the health-related quality-of-life of patients with newly diagnosed
      multiple myeloma aged over 65 years or transplant-ineligible in the pivotal,
      phase III FIRST trial. Patients received: i) continuous lenalidomide and low-dose
      dexamethasone until disease progression; ii) fixed cycles of lenalidomide and low
      dose dexamethasone for 18 months; or iii) fixed cycles of melphalan, prednisone,
      thalidomide for 18 months. Data were collected using the validated questionnaires
      (QLQ-MY20, QLQ-C30, and EQ-5D). The analysis focused on the EQ-5D utility value
      and six domains pre-selected for their perceived clinical relevance. Lenalidomide
      and low-dose dexamethasone, and melphalan, prednisone, thalidomide improved
      patients' health-related quality-of-life from baseline over the duration of the
      study across all pre-selected domains of the QLQ-C30 and EQ-5D. In the QLQ-MY20,
      lenalidomide and low-dose dexamethasone demonstrated a significantly greater
      reduction in the Disease Symptoms domain compared with melphalan, prednisone,
      thalidomide at Month 3, and significantly lower scores for QLQ-MY20 Side Effects
      of Treatment at all post-baseline assessments except Month 18. Linear mixed-model
      repeated-measures analyses confirmed the results observed in the cross-sectional
      analysis. Continuous lenalidomide and low-dose dexamethasone delays disease
      progression versus melphalan, prednisone, thalidomide and has been associated
      with a clinically meaningful improvement in health-related quality-of-life. These
      results further establish continuous lenalidomide and low-dose dexamethasone as a
      new standard of care for initial therapy of myeloma by demonstrating superior
      health-related quality-of-life during treatment, compared with melphalan,
      prednisone, thalidomide. 

PMID- 25769542
TI  - Expression profiling of adult acute lymphoblastic leukemia identifies a BCR-ABL1
      like subgroup characterized by high non-response and relapse rates.

PMID- 25769543
TI  - Rate-limiting roles of the tenase complex of factors VIII and IX in platelet
      procoagulant activity and formation of platelet-fibrin thrombi under flow.
AB  - The importance of factor Xa generation in thrombus formation has not been studied
      extensively so far. Here, we used mice deficient in either factor VIII or factor
      IX to determine the role of platelet-stimulated tenase activity in the formation
      of platelet-fibrin thrombi on collagen. With tissue factor present, deficiency in
      factor VIII or IX markedly suppressed thrombus growth, fibrin formation and
      platelet procoagulant activity (phosphatidylserine exposure). In either case,
      residual fibrin formation was eliminated in the absence of tissue factor. Effects
      of factor deficiencies were antagonized by supplementation of the missing
      coagulation factor. In wild-type thrombi generated under flow, phosphatidylserine
      exposing platelets bound (activated) factor IX and factor X, whereas factor VIII
      preferentially co-localized at sites of von Willebrand factor binding.
      Furthermore, proteolytic activity of the generated activated factor X and
      thrombin was confined to the sites of phosphatidylserine exposure. With blood
      from a hemophilia A or B patient, the formation of platelet-fibrin thrombi was
      greatly delayed and reduced, even in the presence of high concentrations of
      tissue factor. A direct activated factor X inhibitor, rivaroxaban, added to human
      blood, suppressed both thrombin and fibrin formation. Together, these data point
      to a potent enforcement loop in thrombus formation due to factor X activation,
      subsequent thrombin and fibrin generation, causing activated factor X-mediated
      stimulation of platelet phosphatidylserine exposure. This implies that the factor
      VIII/factor IX-dependent stimulation of platelet procoagulant activity is a
      limiting factor for fibrin formation under flow conditions, even at high tissue
      factor concentrations. 

PMID- 25769544
TI  - BCL6--regulated by AhR/ARNT and wild-type MEF2B--drives expression of germinal
      center markers MYBL1 and LMO2.
AB  - Genetic heterogeneity is widespread in tumors, but poorly documented in cell
      lines. According to immunoglobulin hypermutation analysis, the diffuse large B
      cell lymphoma cell line U-2932 comprises two subpopulations faithfully
      representing original tumor subclones. We set out to identify molecular causes
      underlying subclone-specific expression affecting 221 genes including surface
      markers and the germinal center oncogenes BCL6 and MYC. Genomic copy number
      variations explained 58/221 genes differentially expressed in the two U-2932
      clones. Subclone-specific expression of the aryl-hydrocarbon receptor (AhR) and
      the resulting activity of the AhR/ARNT complex underlaid differential regulation
      of 11 genes including MEF2B. Knock-down and inhibitor experiments confirmed that
      AhR/ARNT regulates MEF2B, a key transcription factor for BCL6. AhR, MEF2B and
      BCL6 levels correlated not only in the U-2932 subclones but in the majority of 23
      cell lines tested, indicting overexpression of AhR as a novel mechanism behind
      BCL6 diffuse large B-cell lymphoma. Enforced modulation of BCL6 affected 48/221
      signature genes. Although BCL6 is known as a transcriptional repressor, 28 genes
      were up-regulated, including LMO2 and MYBL1 which, like BCL6, signify germinal
      center diffuse large B-cell lymphoma. Supporting the notion that BCL6 can induce
      gene expression, BCL6 and the majority of potential targets were co-regulated in
      a series of B-cell lines. In conclusion, genomic copy number aberrations,
      activation of AhR/ARNT, and overexpression of BCL6 are collectively responsible
      for differential expression of more than 100 genes in subclones of the U-2932
      cell line. It is particularly interesting that BCL6 - regulated by AhR/ARNT and
      wild-type MEF2B - may drive expression of germinal center markers in diffuse
      large B-cell lymphoma. 

PMID- 25769545
TI  - Key endothelial cell angiogenic mechanisms are stimulated by the circulating
      milieu in sickle cell disease and attenuated by hydroxyurea.
AB  - As hypoxia-induced inflammatory angiogenesis may contribute to the manifestations
      of sickle cell disease, we compared the angiogenic molecular profiles of plasma
      from sickle cell disease individuals and correlated these with in vitro
      endothelial cell-mediated angiogenesis-stimulating activity and in vivo
      neovascularization. Bioplex demonstrated that plasma from patients with steady
      state sickle cell anemia contained elevated concentrations of pro-angiogenic
      factors (angiopoietin-1, basic fibroblast growth factor, vascular endothelial
      growth factor, vascular endothelial growth factor-D and placental growth factor)
      and displayed potent pro-angiogenic activity, significantly increasing
      endothelial cell proliferation, migration and capillary-like structure formation.
      In vivo neovascularization of Matrigel plugs was significantly greater in sickle
      cell disease mice than in non-sickle cell disease mice, consistent with an up
      regulation of angiogenesis in the disease. In plasma from patients with
      hemoglobin SC disease without proliferative retinopathy, anti-angiogenic
      endostatin and thrombospondin-2 were significantly elevated. In contrast, plasma
      from hemoglobin SC individuals with proliferative retinopathy had a pro
      angiogenic profile and more significant effects on endothelial cell proliferation
      and capillary formation than plasma from patients without retinopathy.
      Hydroxyurea therapy was associated with significant reductions in plasma
      angiogenic factors and inhibition of endothelial cell-mediated angiogenic
      mechanisms and neovascularization. Thus, individuals with sickle cell anemia or
      hemoglobin SC disease with retinopathy present a highly angiogenic circulating
      milieu, capable of stimulating key endothelial cell-mediated angiogenic
      mechanisms. Combination anti-angiogenic therapy to prevent the progression of
      unregulated neovascularization and associated manifestations in sickle cell
      disease, such as pulmonary hypertension, may be indicated; furthermore, the
      benefits and drawbacks of the potent anti-angiogenic effects of hydroxyurea
      should be clarified. 

PMID- 25769546
TI  - The impact of graft-versus-host disease prophylaxis in reduced-intensity
      conditioning allogeneic stem cell transplant in acute myeloid leukemia: a study
      from the Acute Leukemia Working Party of the European Group for Blood and Marrow
      Transplantation.
AB  - The impact of the intensity of graft-versus-host-disease immunoprophylaxis on
      transplantation outcomes in patients undergoing transplantation following reduced
      intensity conditioning is unclear. This study addresses this issue in 228 adult
      patients above 50 years of age with acute myeloid leukemia in first complete
      remission given peripheral blood stem cells from HLA-identical siblings after
      fludarabine and 2 days of intravenous busulfan reduced-intensity conditioning. A
      total of 152 patients received anti-thymocyte globulin, either in combination
      with cyclosporine A in 86 patients (group 1), or with cyclosporine A and
      mycophenolate mofetil or short course methotrexate in 66 patients (group 2). The
      remaining 76 patients did not receive anti-thymocyte globulin but were given
      cyclosporine A and methotrexate or mycophenolate mofetil (group 3). Incidences of
      grade II-IV acute graft-versus-host-disease were comparable in the three groups
      (16.5%, 29.5% and 19.5% in groups 1, 2 and 3, respectively, P=0.15). In
      multivariate analysis, the absence of anti-thymocyte globulin was the only factor
      associated with a higher risk of chronic graft-versus-host-disease (P=0.005),
      while the use of triple immunosuppression (group 3) was associated with an
      increased risk of relapse (P=0.003). In comparison to anti-thymocyte globulin and
      cyclosporine A alone, the other two strategies of graft-versus-host-disease
      prophylaxis were associated with reduced leukemia-free survival and overall
      survival (P=0.001 for each parameter), independently of the dose of anti
      thymocyte globulin. These data suggest that fine tuning of the intensity of this
      prophylaxis can affect the outcome of transplantation and that anti-thymocyte
      globulin and cyclosporine A alone should be the preferred combination with the
      fludarabine-busulfan reduced-intensity conditioning regimen and sibling donors. 

PMID- 25769548
TI  - Re: Cystectomy for refractory hemorrhagic cystitis: contemporary etiology,
      presentation and outcomes: B. J. Linder, R. F. Tarrell and s. A. Boorjian j urol
      2014; 192: 1687-1692.

PMID- 25769547
TI  - High-throughput mutational screening adds clinically important information in
      myelodysplastic syndromes and secondary or therapy-related acute myeloid
      leukemia.

PMID- 25769550
TI  - Re: The natural history of clinically complete responders to neoadjuvant
      chemotherapy for urothelial carcinoma of the bladder: A. Meyer, R. Ghandour, A.
      Bergman, C. Castaneda, M. Wosnitzer, G. Hruby, M. Benson and J. McKiernan J Urol
      2014; 192: 696-701.

PMID- 25769551
TI  - Re: Level III-IV inferior vena caval thrombectomy without cardiopulmonary bypass:
      long-term experience with intrapericardial control: M. B. Patil, J. Montez, J.
      Loh-Doyle, J. Cai, E. C. Skinner, A. Schuckman, D. Thangathurai, D. G. Skinner
      and S. Daneshmand.

PMID- 25769552
TI  - Fibromyalgia.

PMID- 25769553
TI  - The effects of different levels of catalase and superoxide dismutase in modified
      Beltsville extender on rooster post-thawed sperm quality.
AB  - Oxidative damage of sperm by means of reactive oxygen species generated by the
      cellular components of semen is one of the main reasons for decreased sperm
      motility and fertility during the freeze-thawing process. This study was
      conducted to determine the influence of catalase (CAT) and superoxide dismutase
      (SOD) on rooster sperm motility, viability and MDA level after freezing and
      thawing. Semen samples from 10 sexually-mature Ross 308 breeder roosters were
      collected and pooled, divided into nine equal parts and diluted with modified
      Beltsville extender containing no antioxidants (control), or supplemented with
      50, 100, 200 and 300 MUg/mL CAT, or 50, 100, 200 and 300 U/mL SOD. After thawing,
      sperm motility and motion parameters were assessed using a CASA system. Sperm
      viability and MDA level were assessed by eosin-nigrosin and MDA test,
      respectively. The results of this experiment showed that the extender
      supplemented with 100 and 200 MUg CAT, and 50 U SOD had the highest sperm
      motility (P<0.05) in sperm motility. Also, addition 100, 200 and 300 MUg CAT, and
      50 U SOD can improve significantly viability after freeze-thaw. Extender
      supplemented with 100 MUg CAT had significantly lower MDA level compared to
      control and 300 MUg CAT. In conclusion, the results of the present study
      demonstrate that addition of CAT (100 MUg/mL) and SOD (50 U/mL) independently
      have beneficial effect on quality of post-thawed rooster semen.

PMID- 25769554
TI  - Hippocampal modifications in transient global amnesia.
AB  - Transient global amnesia (TGA) is an acute and transient syndrome with a
      remarkably stereotypical set of signs and symptoms. It is characterized by the
      abrupt onset (no forewarning) of massive episodic memory impairment, both
      anterograde and retrograde. Ever since it was first described, TGA has fascinated
      neurologists and other memory experts, and in recent years, there has been a
      surge of neuroimaging studies seeking to pin down the brain dysfunction
      responsible for it. Several pathophysiological hypotheses have been put forward,
      including the short-lived suggestion of an epileptic mechanism. All the available
      data indicate that the brain modifications are reversible, and that the mechanism
      behind TGA is of a functional nature. However, while diffusion-weighted imaging
      studies have clearly identified the hippocampus and, more specifically, the CA1
      area, as the locus of brain modifications associated with TGA, researchers have
      yet to determine whether the origin of the mechanism is vascular or
      neurochemical. Spectroscopy may provide a means of settling this issue once and
      for all. 

PMID- 25769555
TI  - Employment after liver transplantation: a review.
AB  - BACKGROUND: Return to productive employment is often an important milestone in
      the recovery and rehabilitation process after liver transplantation (OLT). This
      literature review identifies factors associated with employment in patients who
      underwent OLT. METHODS: We searched PubMed for articles that addressed the
      various factors affecting employment after OLT. RESULTS: The studies demonstrated
      improvement in the quality of life and examined factors that predicted whether
      patients would return to work after OLT. Demographic variable associated with
      posttransplant employment included young age, male sex, college degree, Caucasian
      race, and pretransplant employment. Patients with alcohol-related liver disease
      had a significantly lower rate of employment than did those with other etiologies
      of liver disease. Recipients who were employed after transplantation had a
      significantly better posttransplant functional status than did those who were not
      employed. CONCLUSION: Economic pressures are increasing the expectation that
      patients who undergo successful OLT will return to work. Thus, transplant teams
      need to have a better understanding of posttransplant work outcomes for this
      vulnerable population, and greater attention must be paid to the full social
      rehabilitation of transplant recipients. Specific interventions for OLT
      recipients should be designed to evaluate and change their health perceptions and
      encourage their return to work.

PMID- 25769557
TI  - Survey of the knowledge, perception, and attitude of medical students at the
      University of Leeds toward organ donation and transplantation.
AB  - BACKGROUND: The shortage of organ donors is the key rate-limiting factor for
      organ transplantation in the United Kingdom. Many strategies have been proposed
      to increase donation; one strategy aims to improve awareness of organ donation
      and transplantation (ODT) among medical students. This survey seeks to
      investigate the knowledge, perceptions, and attitudes of the medical students in
      the United Kingdom toward ODT and the curriculum content. METHODS: A 32-item
      online questionnaire was distributed to 957 medical students at the University of
      Leeds (October to December 2012). RESULTS: There were 216 (22.6%) respondents.
      Students were aware of kidney, heart, and liver transplantation (91.6%, 88.8%,
      and 86.5%). Awareness of small intestine (36.7%) and islet of Langerhans (33.0%)
      transplantation was poor. Students understood the term "brain stem death"
      (82.3%); however, they lacked understanding of criteria used for brain stem death
      testing (75.8%). Their perceptions and attitudes were favorable toward ODT; 43.3%
      of the students were unhappy with their current knowledge, and 87.6% of the
      students agree that ODT teaching should be included in the curriculum.
      CONCLUSIONS: Students have a basic understanding of ODT but lack detailed
      knowledge. They accept its importance and desire further teaching to supplement
      their current knowledge to be able to understand the issues related to ODT.

PMID- 25769556
TI  - Mistrust, misperceptions, and miscommunication: a qualitative study of
      preferences about kidney transplantation among African Americans.
AB  - BACKGROUND: Kidney transplantation rates in the United States are lower among
      African Americans than among whites. Well-documented racial disparities in access
      to transplantation explain some, but not all, of these differences. Prior survey
      based research suggests that African American dialysis patients are less likely
      than whites to desire transplantation, but little research has focused on an in
      depth exploration of preferences about kidney transplantation among African
      Americans. Thus, the purposes of this study were to explore preferences and to
      compare patients' expectations about transplantation with actual status on the
      transplant list. METHODS: We conducted semistructured interviews with 16 African
      Americans receiving chronic hemodialysis. We analyzed the interviews using the
      constant comparative method of qualitative analysis. We also reviewed the
      dialysis center's transplant list. RESULTS: Four dominant themes emerged: (1)
      varied desire for transplant; (2) concerns about donor source; (3) barriers to
      transplantation; and (4) lack of communication with nephrologists and the
      transplantation team. A thread of mistrust about equity in the transplantation
      process flowed through themes 2-4. In 7/16 cases, patients' understanding of
      their transplant listing status was discordant with their actual status.
      CONCLUSIONS: Our study suggests that many African Americans on hemodialysis are
      interested in kidney transplantation, but that interest is often tempered by
      concerns about transplantation, including misconceptions about the risks to
      recipients and donors. Mistrust about equity in the organ allocation process also
      contributed to ambivalence. The discordance between patients' perceptions of
      listing status and actual status suggests communication gaps between African
      American hemodialysis patients and physicians. Clinicians should avoid
      interpreting ambivalence about transplantation as lack of interest.

PMID- 25769558
TI  - "Hanging donors": are we still skeptical about the lungs?
AB  - BACKGROUND: Suicidal hanging may cause compression of the neck blood vessels and
      the airway leading, to hypoxic brain damage caused by cerebral ischemia and
      respiratory distress. Hanging engenders global tissue hypoxia, particularly
      affecting the lungs as the result of pulmonary edema and barotrauma. There is
      scant evidence about outcomes of transplantation with the use of lungs from
      "hanging donors." This study evaluates the outcomes of lung transplantations
      (LTx) that use organs from this group. METHODS: We retrospectively analyzed lung
      "organ offers" and LTx at our center between January 2007 and November 2013. The
      outcomes of LTx with lungs from donors with hanging as the cause of death
      ("hanging group") were compared with those with donors having other causes of
      death (control group), with the use of an unadjusted model as well as propensity
      score matching. RESULTS: LTx (n = 302) were performed during this period and were
      grouped on the basis of the cause of death in donors: the hanging group (n = 8)
      and the control group (n = 294). No statistically significant difference was
      found in the donor characteristics except for the incidence of cardiac arrest,
      which was significantly higher in hanging donors. Preoperative characteristics in
      recipients in both groups were comparable. Intra-operative and post-LTx variables
      including PaO2/FiO2 ratios, duration of mechanical ventilation, and intensive
      care unit and hospital stays were comparable. One-year and 3-year survival rates
      were also comparable in both groups. Two recipients in the hanging group required
      extracorporeal life support after LTx and could not survive. CONCLUSIONS:
      Suicidal hanging is a relatively rare cause of death for potential organ donors.
      Because it does not appear to negatively affect outcomes after LTx, it should not
      be considered per se a contraindication for lung donation. A word of caution is
      necessary until we gather larger experience with lungs from hanging donors.

PMID- 25769559
TI  - A new HLA allocation procedure of kidneys from deceased donors in the current era
      of immunosuppression.
AB  - INTRODUCTION: It has recently been proposed to replace the current Eurotransplant
      kidney allocation based primarily on mismatches (MM) at the 3 HLA loci by a
      simpler system based on full HLA-DR compatibility. The present study analyzes
      this system in the current era of immunosuppression. METHODS: From 1999 to 2012,
      723 renal grafts were performed on 586 patients who were treated with a
      calcineurin inhibitor, mycophenolate mofetil, and in most cases antilymphocyte
      globulins. Four groups of HLA MM were compared: (A) A+B 2-4/DR 1-2 MM (n = 397),
      (B) A+B 2-4 MM/DR 0 MM (n = 106), (C) A+B 0-1 MM/DR 1-2 MM (n = 138), and (D) A+B
      0-1/DR 0 MM (n = 82). RESULTS: Acute rejection episodes were less frequent during
      the first post-transplantation year in group D than in the other groups (P =
      .018). Patient survival was lower in group A than in the other groups (P = .008).
      Immunologic graft survival was higher in group D than in the other groups in
      univariate (P = .015) and multivariate analyses (P = .033; 96.4% vs 90.1% at 10
      years). CONCLUSIONS: In the current era of immunosuppression, allocation of
      kidneys from deceased donors could be performed primarily according to full DR
      compatibility then to the best A+B matching, affording excellent graft outcome to
      most recipients.

PMID- 25769560
TI  - Protective effect of Berberine pretreatment in hepatic ischemia/reperfusion
      injury of rat.
AB  - BACKGROUND: Berberine (BBR) has been demonstrated to protect against hepatic
      ischemia/reperfusion (I/R) injury. However, the exact mechanism is largely
      unknown. In the present study, we examined the role of phosphatidylinositol 3
      kinase/protein kinase B (PI3K/Akt) and mammalian target of rapamycin (mTOR) in
      the protective effect of BBR on hepatic I/R-mediated apoptosis in rats. METHODS:
      Adult male Sprague-Dawley rats were assigned randomly to groups of sham,
      ischemia/reperfusion (I/R), I/R+DMSO (vehicle) and I/R+BBR (100 mg/kg/d, 2
      weeks). The hepatic cold ischemia model was established by perfusing the liver
      with heparinized cold saline through the portal vein for 20 minutes. The liver
      function and oxidative stress level were measured by biochemical and
      histopathologic examinations. The apoptotic rate was determined by terminal
      deoxynucleotidyl transferase biotin-dUTP nick end labeling (TUNEL) assay. The
      expression of Bcl-2, Bax, caspase-3, and the phosphorylation of Akt and mTOR were
      assayed by Western blot analysis and immunohistochemistry. RESULTS: Compared with
      the I/R group, BBR dramatically attenuated the histopathologic damage, restored
      the liver function, and decreased the oxidative stress level. Simultaneously, BBR
      significantly ameliorated apoptosis by decreasing the apoptotic rate, increasing
      the Bcl-2/Bax ratio and inhibiting cleaved caspase-3 expression in rats subjected
      to hepatic I/R. The expression of p-Akt were effectively upregulated with the
      inhibited expression of p-mTOR. CONCLUSION: Our study reveals that BBR
      preconditioning protects against hepatic I/R partly by reducing apoptosis, which
      is possibly involved with the modulation of the PI3K/Akt/mTOR signaling pathway.

PMID- 25769561
TI  - Erythropoietin pretreatment exerts anti-inflammatory effects in hepatic
      ischemia/reperfusion-injured rats via suppression of the TLR2/NF-kappaB pathway.
AB  - INTRODUCTION: The inflammatory response plays an important role in liver
      dysfunction after hepatic ischemia/reperfusion (I/R), which is tightly regulated
      by the Toll-like receptor 2 (TLR2)/nuclear factor (NF)-kappaB pathway;
      suppression of TLR2/NF-kappaB signaling has therefore become a promising target
      for anti-inflammatory treatment in hepatic I/R injury. Erythropoietin (EPO) is a
      glycoprotein cytokine produced primarily by the kidney that has anti-inflammatory
      activities. The purpose of the present study was to investigate the effect of EPO
      preconditioning, if any, against hepatic I/R injury in rats and its underlying
      mechanisms. MATERIALS AND METHODS: Male Sprague-Dawley rats were subjected to
      partial (70%) hepatic ischemia for 45 minutes after pretreatment with either
      saline or EPO followed by 24-hour reperfusion. Hepatic injury was evaluated
      according to biochemical and histopathologic examinations. The expression of
      tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta), and
      interleukin-6 (IL-6) were measured by using enzyme-linked immunosorbent assay and
      real-time polymerase chain reaction. The expression of nuclear translocation and
      phosphorylation of NF-kappaB p65, EPOR receptor (EPOR), p-EPOR, p-IkappaB-alpha,
      IkappaB-alpha, and TLR2 were determined by using Western blot analysis. RESULTS:
      EPO treatment significantly improved hepatic function and histology, as indicated
      by reduced transaminase levels and pathologic changes. The expression of TNF
      alpha, IL-1beta, IL-6, p-IkappaB-alpha, and TLR2 was significantly decreased with
      up-regulation of p-EPOR by EPO. Moreover, EPO pretreatment also reduced I/R
      induced the phosphorylation and nuclear translocation of NF-kappaB p65 subunits
      in liver tissue, but EPO had no influence on the expression of p65 and IkappaB
      alpha. CONCLUSIONS: These results suggest that EPO pretreatment ameliorates
      hepatic I/R injury, which is involved in suppressing TLR2/NF-kappaB-mediated
      inflammation.

PMID- 25769562
TI  - Impact of metabolic syndrome on postdonation renal function in living kidney
      donors.
AB  - INTRODUCTION: Optimization of kidney donor selection is critical to ensure
      recovery of the donor. The goal of this study was to determine the influence of
      metabolic syndrome on renal histology and perioperative renal function in living
      kidney donors. PATIENTS AND METHODS: Between January 2010 and March 2013, a total
      of 363 living kidney donors who underwent donor nephrectomy at our institution
      were enrolled. Metabolic syndrome was diagnosed in patients according to the
      National Cholesterol Education Program's Adult Treatment Panel III, and renal
      histology of implantation biopsy specimens and perioperative renal function were
      compared in participants with or without metabolic syndrome. Using multivariate
      regression analysis, the goal was to identify which component of metabolic
      syndrome induces chronic histologic changes and delayed renal function recovery.
      RESULTS: We identified 30 donors (8.45%) with metabolic syndrome. Donors with
      metabolic syndrome were older (48.4 +/- 9.2 years vs 39.7 +/- 11.4 years; P <
      .001) and more likely to have chronic histologic changes (36.8% vs 9.7%; P =
      .001) than subjects without metabolic syndrome. Results of the multivariate
      regression analysis indicated that obesity, hyperglycemia, and
      hypertriglyceridemia were independently associated with chronic histologic
      changes. Perioperative renal function was correlated with the presence of
      metabolic syndrome rather than with chronic histologic changes, and patients with
      metabolic syndrome were more likely to experience delayed renal function
      recovery. Linear regression models found that the sum of the metabolic components
      correlated with renal function 6 months postoperatively, but among all risk
      factors, only obesity was significantly associated with the occurrence of delayed
      renal function recovery (odds ratio, 2.67; P = .001). CONCLUSIONS: Although
      metabolic syndrome in living kidney donors is characterized by chronic histologic
      changes, perioperative renal function is affected by the syndrome itself rather
      than by the histologic changes. Obesity is the most important metabolic factor
      for predicting delayed renal function recovery in living kidney donors, providing
      an important clinical indicator of postoperative renal function in these
      patients.

PMID- 25769563
TI  - Dobutamine stress echocardiography in the diagnosis of asymptomatic ischemic
      heart disease in patients with chronic kidney disease--review of literature and
      single-center experience.
AB  - BACKGROUND: Coronary artery disease (CAD) may be present in kidney transplant
      (KT) candidates without the presence of CAD clinical symptoms. This study joins
      an ongoing discussion about appropriate noninvasive diagnostic approaches for
      ischemic heart disease (IHD) assessment and patient selection for
      revascularization procedures. The aim of this study was to evaluate the role of
      dobutamine stress echocardiography (DSE) in IHD diagnosis in initially
      asymptomatic maintenance hemodialysis (HD) patients. METHODS: Forty HD patients
      aged 52.4 +/- 2.0 years, were studied for 2.5 years. At inclusion, they were free
      of both symptoms and history of IHD. Standard electrocardiography (ECG), chest X
      ray, standard echocardiography, DSE, 24-hour Holter ECG, and Doppler
      ultrasonography (carotids and lower extremities) were performed. Results were
      analyzed according to a predefined diagnostic algorithm. RESULTS: DSE yielded
      negative results in all patients. Left ventricular (LV) ejection fraction <= 60%,
      LV hypertrophy, and Holter ECG silent ischemia features were noticed in 15%, 70%,
      and 10% of patients, respectively. Atherosclerotic lesions in lower extremities
      and carotid arteries were present in 50% and 37.5% of patients, respectively.
      During the follow-up, 9/40 patients died, including 6 cardiovascular (CV) deaths:
      2 with intermediate and 4 with high CV risk according to the proposed algorithm.
      CONCLUSIONS: In asymptomatic KT candidates, not only DSE, but also other
      noninvasive tests (eg, echocardiography and Doppler ultrasonography of the
      carotid and peripheral arteries) along with a detailed profile of the remaining
      CV risk factors should be performed and analyzed. Defined composition of risk
      factors and particular changes in noninvasive tests may be an indication for
      coronary angiography.

PMID- 25769564
TI  - Increased urine transforming growth factor beta1 (TGF-beta1) and serum uric acid
      are associated with an early decline of glomerular filtration rate in kidney
      transplant recipients.
AB  - BACKGROUND: The renin-angiotensin system (RAS) and transforming growth factor
      beta1 (TGF-beta1) may play a role in the pathogenesis of fibrosis in kidney
      allografts. Experimental hyperuricemia shows activation of intrarenal RAS.
      However, the association between uric acid (UA), RAS, and TGF-beta1 in allograft
      recipients has not been demonstrated. Therefore we investigated the association
      between serum UA levels, RAS, and TGF-beta1 in kidney transplant recipients
      during the 1st year after transplantation. METHODS: Sixty-two transplant
      recipients were included in the study. Serum UA level, plasma renin activity
      (PRA), and urine TGF-beta1 concentration were studied at 3, 6, and 12 months
      after transplantation. Statistical correlation was demonstrated with the use of
      Spearman rank correlation coefficient. Receiver operating characteristic curve
      analysis and area under the curve were performed to assess the diagnostic
      performance to discriminate between estimated glomerular filtration rate (eGFR)
      <60 and >= 60 mL/min/1.73 m(2). RESULTS: For all 62 patients, urine TGF-beta1 and
      serum UA had a tendency to increase during the 1-year follow-up period, despite
      no statistically significant change in eGFR. We found that increased urine TGF
      beta1 was correlated with rising serum UA levels and a decrease of the eGFR (r =
      0.27 [P = .01]; r = -0.38 [P = .0003]). In contrast, there was no significant
      change in PRA and it was not correlated with eGFR or TGF-beta1 (r = -0.01; P =
      .93). CONCLUSIONS: Increased urine TGF-beta1 and serum UA level during the 1st
      year after transplantation correlated with a decline in eGFR. The evaluation of
      these parameters in the early post-transplantation period may identify patients
      at risk of allograft dysfunction.

PMID- 25769565
TI  - Strength of donor-specific antibodies with the use of Luminex single-antigen
      beads is a reliable predictor of acute rejection in living-relative kidney
      recipients.
AB  - BACKGROUND: Luminex single-antigen assay is a promising technique for
      determination of donor-specific antibodies (DSAs) in renal transplantation.
      METHODS: Serum samples from living-relative renal recipients before and after
      renal transplantation were examined with the use of Luminex single-antigen assay.
      The impact of de novo DSAs on the early clinical outcomes of renal allograft was
      analyzed. RESULTS: Of the 61 patients included, 15 patients (24.6%) presented de
      novo DSA (4 class I, 4 class II, and 7 both classes) after transplantation, and
      the average (median) cumulative strength of DSA was 1,283 (range, 0-10,802) mean
      fluorescence index (MFI) for class I versus 1,324 (range, 0-14,985) MFI for class
      II (P > .05). Twelve (19.7%) of the 61 patients experienced a
      clinical/subclinical acute rejection (AR) episode within the 1st 2 years after
      transplantation. A clinical/subclinical AR episode was diagnosed in 40% of DSA(+)
      patients and 13.0% of DSA(-) patients (P < .05). DSA(+) patients who developed an
      AR episode had a higher mean cumulative MFI value (8,118.3 +/- 5,287.4; range,
      1,785-14,985) than patients who did not develop an AR episode (3,283.7 +/-
      2,601.0; range, 786-8,113; P < .05). Serum creatinine levels in the DSA(+) group
      were significantly higher than in the DSA(-) group at 12 and 24 months after
      transplantation. The graft survival rates at 2 years in the DSA(+) and DSA(-)
      groups were not different (86.7% vs 91.3%; P > .05). CONCLUSIONS: Patients with
      de novo DSAs at high strength may suffer a high risk of developing an AR episode.
      Therefore, careful monitoring of de novo DSAs with the use of Luminex single
      antigen beads may help in early intervention for AR in renal allografts and to
      minimize renal damage caused by the antibodies.

PMID- 25769566
TI  - Clinical significance of monitoring serum level of matrix metalloproteinase 9 in
      patients with acute kidney allograft rejection.
AB  - This study was designed to explore the clinical significance of dynamically
      monitoring the serum level of matrix metalloproteinase 9 (MMP-9) before and after
      renal transplantation. Before transplantation and 1, 3, 5, 7, 10, 15, and 20 days
      after transplantation, the peripheral blood was collected from 102 renal
      transplant recipients, including 8 with acute rejection (ARs) and 94 non-ARs. The
      serum MMP-9 level was detected by Luminex 200 analyzer (Luminex Corporation,
      Austin, TX, USA). By day 3 post-transplantation, the serum MMP-9 level in non-ARs
      had significantly reduced as compared to the pretransplantation level, and
      reached the lowest value on day 20 post-transplantation. In contrast, the serum
      MMP-9 level in ARs had significantly increased by day 3, reached the highest
      value on day 7, and remained significantly higher on day 20 as compared to the
      pretransplantation level. The receiver operating characteristic curve was plotted
      to evaluate the power of serum MMP-9 level on day 20 post-transplantation to
      differentiate the non-AR and AR groups. Our data revealed that with a threshold
      of 8473.26 pg/mL, the area under the curve was 0.758 (0.661, 0.856); the
      sensitivity and specificity of the diagnostic were 78.40% and 61.30%,
      respectively; the positive and the negative predictive values were 74.60% and
      66.67%, respectively; and the accuracy rate was up to 71.57%. Taken together, the
      results indicated that dynamically monitoring serum MMP-9 levels in renal
      allograft recipients might be a convenient and safe method to diagnose ARs.

PMID- 25769567
TI  - Quantitative proteomic profiling of renal tissue in human chronic rejection
      biopsy samples after renal transplantation.
AB  - INTRODUCTION: Chronic rejection (CR) is the leading cause of late renal
      transplant failure and is characterized by a relatively slow but progressive loss
      of renal function in combination with proteinuria and hypertension >3 months
      after transplantation. To identify and quantify the protein profiles in renal
      tissues of CR patients, we used isotope tagging for relative and absolute
      quantification (iTRAQ)-based proteomic technology to perform global protein
      expression analyses in CR patients and control subjects. MATERIALS AND METHODS:
      After protein extraction, quantitation, and digestion, samples were labeled with
      iTRAQ reagents and then separated by strong cation exchange and high-performance
      liquid chromatography. The fractions were further analyzed by tandem mass
      spectrometry. ProteinPilot version 4.0 software and the Swiss-Prot human database
      were applied for statistical analysis and database searching, respectively.
      Differentially expressed proteins were subjected to bioinformatic analysis by
      using the Gene Ontology database and the Kyoto Encyclopedia of Genes and Genomes
      database to further characterize their potential functional roles and related
      pathways in CR. RESULTS: In total, 1857 distinct proteins (confidence >95%, rho <
      .05) were identified and quantified. Using a strict cutoff value of 1.5-fold for
      expressed variation, 87 proteins showed significant differences in expression
      between the CR and control groups; 53 were up-regulated and 34 were down
      regulated. The differentially expressed proteins were mainly involved in protein
      binding, structural molecule activity, and extracellular matrix structural
      constituent. Several proteins, such as the alpha-1 chain of collagen type IV and
      integrin alpha-1, may play roles in the pathogenesis of CR and were implicated in
      the extracellular matrix-receptor interaction pathway. CONCLUSIONS: This study is
      the first to focus on iTRAQ-based quantitative proteomic characterization of
      renal tissue in CR. These insights may broaden our understanding of the molecular
      mechanisms underlying CR and provide potential biomarker candidates for future
      diagnostics.

PMID- 25769568
TI  - Association between post-transplantation immunoglobulin A deposition and reduced
      allograft function.
AB  - BACKGROUND: Post-transplantation de novo and recurrent immunoglobulin A (IgA)
      deposition (IgAD) in the allograft is commonly observed. However, the association
      between post-transplantation IgAD and reduced allograft function has not been
      determined. We therefore investigated the association between reduced allograft
      function and post-transplantation IgAD using serial allograft biopsies. METHODS:
      IgAD was retrospectively analyzed in 45 adults who underwent kidney
      transplantation for chronic glomerulonephritis, including IgA nephropathy, at
      Kagawa University Hospital. Allograft biopsy samples were obtained from per
      protocol biopsies obtained 1 and 3 years after transplantation, as well as from
      episode biopsies. Factors contributing to post-transplantation IgAD were assessed
      by calculating adjusted odds ratios (AORs) using logistic regression analysis.
      RESULTS: Of the 45 recipients, 18 had post-transplantation allograft IgAD. The
      estimated glomerular filtration rates (eGFR) 1, 2, and 3 years after
      transplantation were lower in the recipients with than without IgAD. Urinalysis
      was normal in 61% of recipients with IgAD. Reduced allograft function (eGFR <40
      mL/min/1.73 m(2)) 1 year after transplantation was significantly associated with
      post-transplantation IgAD (AOR = 34.4 [95% CI = 2.35-502], P = .01). Conversely,
      blood concentrations of mycophenolic acid and latent IgAD from donor kidneys were
      not significantly associated with post-transplantation IgAD. CONCLUSION: Reduced
      allograft function may be associated with post-transplantation IgAD in the
      allograft.

PMID- 25769569
TI  - Serum miR-338-5p, soluble B-cell-activating factor, allo-antibodies, and renal
      transplantation.
AB  - BACKGROUND: The objective of the study was to explore the expression features of
      serum miR-338-5p and soluble B-cell-activating factor (sBAFF) in renal transplant
      recipients. METHODS: Follow-up renal transplant recipients (n = 49) were enrolled
      in this study (male/female: 38/11). Healthy volunteers were controlled; 2 mL of
      peripheral blood from each subject was collected. Total RNA was extracted from
      serum by use of the miRNeasy Serum/Plasma Kit (QIAGEN), and miR-338-5p was
      amplified by means of quantitative real-time reverse transcriptase-polymerase
      chain reaction. sBAFF was detected by means of enzyme-linked immunoassay.
      LABScreen Mix (LSM12) (One Lambda) was used to test the level of anti-human
      leukocyte antigen (HLA) I antibody (Ab), anti-HLA II Ab, and anti-major
      histocompatibility complex class I chain-related A (MICA) Ab. All data are shown
      as mean +/- SD and were analyzed by use of SPSS software 17.0. RESULTS: Compared
      with healthy volunteers, serum miR-338-5p in recipients was statistically
      downregulated (2.79 +/- 2.5 versus 0.09 +/- 0.12, P < .001); sBAFF in recipients
      was significantly upregulated (1321 +/- 950 pg/mL versus 534 +/- 327 pg/mL, P <
      .01); serum anti-HLAII Ab, anti-MICA Ab, and anti-HLA+MICA Abs all statistically
      increased in recipients (P < .05). Spearman correlation analysis showed that miR
      338-5p was significantly negatively correlated with sBAFF (r = -0.51, P < .001)
      and anti-HLA II antibody with mean fluorescence intensity value >1000 (r = 
      0.322, P < .05). Analysis results also suggested that sBAFF was significantly
      negatively correlated with anti-MICA Ab, with mean fluorescence intensity value
      >1000 (r = -0.579, P < .05). CONCLUSIONS: miR-338-5p is closely correlated with
      the procedure of renal allograft antibody-mediated rejection.

PMID- 25769570
TI  - Endothelial dysfunction in renal transplant recipients: role of vitamin D and
      fibroblast growth factor-23.
AB  - BACKGROUND: Endothelial dysfunction can be detected at early stages of chronic
      kidney disease. Although endothelial functions improve after successful renal
      transplantation, renal transplant recipients have still worse endothelial
      functions compared to healthy subjects. Vitamin D deficiency and high fibroblast
      growth factor-23 (FGF-23) levels may have a role on endothelial dysfunction in
      chronic kidney disease patients. The aim of this study is to investigate the
      association between endothelial functions, vitamin D, and FGF-23 levels in renal
      transplant recipients. METHODS: One hundred nine renal transplant recipients (71
      male, 38 female) underwent brachial flow-mediated dilatation (FMD), serum 25-OH
      vitamin D, and FGF-23 level measurements. Vitamin D and FGF-23 levels were
      compared between patients with normal and abnormal endothelial functions.
      Correlations between FMD, vitamin D, and FGF-23 were also investigated. RESULTS:
      Endothelial functions were abnormal in 72.5% of the patients. Prevalence of
      vitamin D deficiency was 80.7%. Vitamin D levels were significantly lower in
      patients with endothelial dysfunction compared to patients with normal
      endothelial functions (12.6 +/- 6.6 MUg/L vs 17.3 +/- 10.0 MUg/L respectively, P
      = .02). FGF-23 levels were not different between the two groups. 25-OH vitamin D
      levels had a significant positive correlation with amount of FMD (r = 0.218 and P
      = .02) and were an independent predictor of FMD after adjusting for potential
      confounding factors including age, transplantation duration, body mass index,
      mean blood pressure, glomerular filtration rate, proteinuria, hemoglobin, and FGF
      23 in multivariate regression analysis (beta = 0.194, P = .04). FGF-23 levels
      were not predictive of FMD in this model (beta: -0.125, P = .197) CONCLUSION:
      Vitamin D deficiency is associated with endothelial dysfunction in renal
      transplant recipients. Further clinical and experimental studies are necessary to
      define a causal relationship between the parameters, discover the potential
      mechanisms, and observe the effect of vitamin D replacement on endothelial
      functions in renal transplant recipients.

PMID- 25769571
TI  - Survival of renal transplant patients: data from a tertiary care center in
      Turkey.
AB  - OBJECTIVE: Data on transplantation survival is widely available for developed
      countries where cadaveric transplantation is the dominant transplantation type.
      We aimed to assess patient and graft survival and to determine the possible
      factors affecting graft survival in a developing country where kidney
      transplantations were mainly performed from living donors. METHODS: We
      retrospectively analyzed data from 427 adult kidney transplantations performed at
      our center from January 1990 to November 2010. We collected data from patient
      files, including characteristics of the recipients and donors, transplantation
      related factors, post-transplantation features, causes of graft loss, and patient
      death. The Kaplan-Meier method was used to analyze survival, and Cox regression
      analysis was used to evaluate the effects of multiple factors on graft survival.
      RESULTS: Most of the recipients (82.6%) received their organs from living donors.
      One-year and 5-year graft survival rates were 87.5% and 78.3%, respectively,
      where the 5-year graft survival rates were 87.1% for living donors and 74.8% for
      cadaveric donors. The 1-year and 5-year patient survival rates were 90.9% and
      88.9%, respectively. Univariate analysis showed that predictors for better graft
      survival were serum creatinine levels <1.5 mg/dL at 1 month after
      transplantation, proteinuria <500 mg/d at 1 year after transplantation, use of
      tacrolimus and mycophenolic acid derivative-based immunosuppression at baseline,
      living-donor transplantation, and transplantations performed in the years 2000
      2010. CONCLUSIONS: We report data on kidney transplantation in an emerging
      country where living-donor transplantation constitutes a large proportion of
      kidney transplant activities. Modern immunosuppressive medications help to
      achieve a better survival. Our 5-year results are similar to those of developed
      countries.

PMID- 25769572
TI  - C/EBP homologous protein-mediated endoplasmic reticulum stress-related renal
      apoptosis is involved in rats with brain death.
AB  - BACKGROUND: C/EBP homologous protein (CHOP) is an important marker in endoplasmic
      reticulum stress (ERS)-associated cell apoptosis. The role of CHOP-induced renal
      apoptosis remains unclear in rats with brain death (BD). The present study aims
      to investigate the possible implication of CHOP-mediated, ERS-related BD-induced
      apoptosis in rats. MATERIALS AND METHODS: Forty male Sprague-Dawley rats were
      divided randomly into 4 experimental groups. We examined activation of ERS and
      apoptosis-related protein expression using Western blot and immunohistochemical
      staining. In addition, apoptosis is assessed by terminal deoxynucleotide
      transferase-mediated dUTP nick-end labeling assay. RESULTS: Kidneys harvested
      after BD show increased ERS- and apoptosis-related protein markers compared with
      kidneys of non-BD rats. Salubrinal (Sal) significantly increased levels of p
      eIF2a and decreased the activity of CHOP at 6 hours after BD compared with
      vehicle-treated dimethylsulfoxide. CONCLUSIONS: Treating the BD donor with Sal
      influences renal apoptosis compared with vehicle-treated BD rats. Our results
      indicate that targeting the CHOP pathway provides a promising therapeutic
      approach for kidney injury associated with donor BD.

PMID- 25769573
TI  - Urinary tract reconstruction using uretero-ureteral end-to-side anastomosis in
      kidney transplant recipients.
AB  - BACKGROUND: In kidney transplant recipients, the most widely used method for the
      reconstruction of the urinary pathway is ureteroneocystostomy, which may be
      difficult in cases with disused atrophic bladder. In this study, we evaluated
      kidney transplant recipients who underwent uretero-ureteral end-to-side
      anastomosis (UUA) in urinary reconstruction due to disused atrophic bladder.
      METHODS: To clarify the effectiveness of this method, we retrospectively reviewed
      the clinical records of kidney transplant recipients in our hospital. RESULTS: A
      total of 9 recipients with urinary reconstruction using UUA were evaluated. All
      of these patients had a history of long-term hemodialysis before transplantation,
      accompanied by complete anuria and small capacity of the bladder. In 4 patients,
      cranial native ureter was ligated, whereas it was not ligated in the remaining 5
      patients. In 2 of 4 patients with cranial ligation, hydronephrosis developed in
      the native kidney with no further treatment being required. No patients
      experienced urinary tract complications including hydronephrosis in the graft,
      urine extravasation, or urinary tract infection in the follow-up period (757.6 +/
      491.3 days). Allograft function was maintained well in all patients (serum
      creatinine level, 1.08 +/- 0.23 mg/dL). CONCLUSIONS: Although UUA is not a
      routine method of urinary reconstruction in kidney transplantation, it can be
      safely performed and should be a surgical option, especially for recipients with
      disused atrophic bladder. The ligation of cranial native ureter may lead to
      hydronephrosis of the native kidney, and it is tentatively concluded that UUA
      without native ureteral ligation is clinically feasible.

PMID- 25769574
TI  - Does allograft size really matter in the long-term outcome of living donor kidney
      transplantation?
AB  - BACKGROUND: Increased allograft mass in living donor kidney transplantation has
      been recognized as a predictor factor of better short-term allograft function. We
      evaluated whether donor kidney volume adjusted for recipient body weight is
      associated with long-term allograft function in living donor kidney
      transplantation. METHODS: We analyzed 67 living donors and their recipients who
      underwent transplantation between 2003 and 2007. Estimated glomerular filtration
      rate (eGFR) and serum creatinine levels at 1, 2, 3, 4, and 5 years post
      transplantation were recorded for all recipients. Transplanted kidney volumes
      were measured using 3-D helical computed tomography scanning. A transplant kidney
      volume-recipient body weight (Vol/Wt) ratio was calculated for each donor
      recipient pair. The subjects were divided into tertiles according to Vol/Wt
      ratios: low (<2.16), medium (2.16-2.88), and high (>2.88). RESULTS: Vol/Wt ratio
      significantly correlated with recipient eGFR and serum creatinine levels at 1, 2,
      3, and 4 years post-transplantation (r = .48, P < .0001; r = .46, P < .0001; r =
      .47, P < .0001; r = .26, P = .037, respectively, for eGFR; r = -.53, P < .0001; r
      = -.50, P < .0001; r = -.44, P < .0001; r = -.37, P = .003, respectively, for
      serum creatinine) but not at 5 years (r = .12, P = .406 for eGFR; r = -.21, P =
      .110 for serum creatinine). Whereas recipient eGFR increased significantly in a
      graded fashion among low to high Vol/Wt ratio groups during 1 to 3 years post
      transplantation, there was no difference in eGFR values between Vol/Wt ratio
      groups at 4 and 5 years (P = .21 and .71, respectively). CONCLUSION: Vol/Wt ratio
      is not associated with long-term allograft function in living donor kidney
      transplantation.

PMID- 25769575
TI  - Nutritional status in Japanese renal transplant recipients with long-term graft
      survival.
AB  - BACKGROUND: Nutritional status affects clinical outcomes in patients with chronic
      renal failure. Glucose intolerance, dyslipidemia, obesity, hypertension, and a
      calcium-phosphorus-vitamin D imbalance are the major nutritional and metabolic
      problems that occur in posttransplant patients. In this study, we assessed the
      daily intake in long-term renal transplant recipients to determine whether they
      have sufficient nutrients based on the Japanese nutrition recommendations
      (recommended dietary allowances [RDA] in Japan 2010). SUBJECTS AND METHODS:
      Thirty-one renal allograft recipients followed for >10 years (median, 16.3) were
      recruited. The median serum creatinine level was 1.2 g/dL (95% CI, 0.6-3.4). We
      estimated the intake of nutrients, including protein and salt, using a simple
      food frequency questionnaire. RESULTS: The median body mass index was 20.1
      kg/m(2). The median total energy intake was 1566 kcal/d (95% CI, 892-2556). The
      daily intake of protein and salt was 65.1 and 9.1 g/d, respectively. The calcium,
      iron, vitamin D, and vitamin K intakes were 423 mg, 7.0 mg/d, 9.7 MUg/d, and 197
      MUg/d, respectively. Patients with dyslipidemia displayed greater amounts of
      lipid and calcium than those with normal lipid levels. DISCUSSION: Our findings
      suggest that long-term renal transplant recipients in Japan seem to restrict
      caloric intake, while maintaining appropriate intake of protein, lipids,
      carbohydrates, and vitamins A, D, and K. However, daily calcium and iron intake
      were insufficient; salt intake was greater than the recommended dietary
      allowances in all subjects. In patients with dyslipidemia, calcium intake was
      lower than those in patients without dyslipidemia, although their intake of
      lipids was also lower than those without dyslipidemia. CONCLUSION: Nutritional
      guidance beginning during the early posttransplant phase helps to foster a
      healthy body mass index and nutritional balances for long-term renal transplant
      recipients. However, greater salt restriction was needed, and additional
      nutritional guidance aiming to prevent osteoporosis seems to be considered.

PMID- 25769576
TI  - Complex kidneys for complex patients: the risk associated with transplantation of
      kidneys with multiple arteries into obese patients.
AB  - Conflicting evidence surrounds clinical outcomes in obese individuals after
      transplantation; nonetheless, many are denied the opportunity to receive a
      transplant. Allografts with complex vascular anatomy are regularly used in both
      deceased and living donor settings. We established the risk of transplanting
      kidneys with multiple renal arteries into obese recipients. A retrospective
      analysis of data from 1095 patients undergoing renal transplantation between
      January 2004 and July 2013 at a single centre was conducted. Of these, 24.2% were
      obese (body mass index >30 kg/m(2)), whereas 25.1% of kidneys transplanted had
      multiple arteries, thereby making the transplantation of kidneys of complex
      anatomy into obese recipients a relatively common clinical occurrence. Vessel
      multiplicity was associated with inferior 1-year graft survival (85.8.% vs 92.1%,
      P = .004). Obese patients had worse 1-graft survival compared to those of normal
      BMI (86.8% vs 93.8%, P = .001). The risk of vascular complications and of graft
      loss within a year after transplantation were greater when grafts with multiple
      arteries were transplanted into obese recipients as compared to their nonobese
      counterparts (RR 2.00, CI 95% 1.07-3.65, and RR 1.95, CI 95% 1.02-3.65).
      Additionally, obese patients faced significantly higher risk of graft loss if
      receiving a kidney with multiple arteries compared to one of normal anatomy (RR
      1.97, 95% CI 1.02-3.72). Thus, obese patients receiving complex anatomy kidneys
      face poorer outcomes, which should be considered when allocating organs, seeking
      consent, and arranging for aftercare.

PMID- 25769577
TI  - Incidence of contrast-induced nephropathy in kidney transplant recipients.
AB  - Contrast-induced nephropathy (CIN) is responsible for one-third of acute kidney
      injuries (AKI) in the hospital setting. The incidence of CIN varies from 3% to
      30%, depending on the preexisting risk factors, with higher incidence noted with
      diabetes mellitus, chronic kidney disease, and older age. Though CIN risk factors
      are common in kidney transplant recipients (KTRs), data about incidence of CIN in
      this population are sparse. METHODS: We retrospectively analyzed 124 consecutive
      patients transplanted at our center between January 2002 and December 2013 and
      received iodinated intravascular contrast with stable kidney function prior to
      contrast administration. CIN was defined as either an absolute rise in serum
      creatinine of >= 0.5 mg/dL or a >= 25% drop in estimated glomerular filtration
      rate (eGFR) after contrast administration. RESULTS: Seven of 124 (5.64%) patients
      developed CIN. Kidney function returned to baseline in 5 of the 7 patients within
      3 weeks. In 2 patients serum creatinine remained elevated due to recurrent AKI
      episodes from other causes. Dialysis was not required in any patient. Calcineurin
      inhibitors (CNIs) were being used in 95% patients at the time of contrast
      administration. Diabetes mellitus, baseline serum creatinine, age, race, gender,
      and the use of ACE inhibitor, angiotensin receptor blocker, diuretic, or
      prophylaxis with intravenous hydration +/- N-acetylcysteine did not affect the
      incidence of CIN. CONCLUSION: Incidence of CIN in KTRs was low in our study
      (5.6%), much less than previously reported. This low incidence may be related to
      the high baseline eGFR (>70 mL/min/1.73 m(2)) and use of hypo-osmolar contrast in
      our patients. In KTRs with baseline eGFR >70 mL/min, the incidence of CIN is low
      despite the concurrent use of nephrotoxic CNI.

PMID- 25769578
TI  - The use of Tenckhoff catheters for draining of symptomatic lymphoceles: a review
      of literature and our experience.
AB  - BACKGROUND: Lymphoceles are one of the common complications of kidney
      transplantations. While small, asymptomatic lypmhoceles do not require
      intervention, however, larger, high-pressure cases can lead to graft dysfunction
      and are thus an indication for decompression. The aim of this study is to present
      the drainage using a Tenckhoff catheter as effective treatment for recurrence of
      symptomatic lymphoceles based on both a single center's experience as well as
      existing literature. MATERIALS AND METHODS: In our database, two patients were
      operated with a Tenckhoff catheter for the recurrence of symptomatic lymphocele.
      A review of MEDLINE in search of cases with lymphoceles treated with Tenckhoff
      catheterization yielded only five articles published between 1990 and 2014. The
      reports covered 15 cases in which 11 patients were treated for a primary
      lymphocele whereas 4 were treated for a recurring lymphocele. RESULTS: There was
      no evidence of lymphocele recurrence or infections after Tenckhoff
      catheterization in either the material review or our database. CONCLUSIONS:
      Intraperitoneal drainage with a Tenckhoff catheter seems to be an effective and
      safe method for treating recurrent, symptomatic lymphoceles after renal
      transplantation.

PMID- 25769579
TI  - Prediction of cardiovascular events after renal transplantation.
AB  - BACKGROUND: Pulse wave velocity (PWV) is a marker of arterial stiffness and
      predicts cardiovascular events in the nontransplantation population.
      Cardiovascular events (CVE) are the leading cause of death and one of the leading
      causes of graft failure in renal transplant recipients. The present prospective
      study investigates whether there is a correlation between PWV and CVE in renal
      transplant recipients. METHODS: A prospective study assessing the incidence of a
      composite cardiovascular endpoint within >= 3 years after pulse wave analysis was
      performed in 64 stable renal transplant recipients. Measurement of PWV,
      augmentation index (AI75), and aortic systolic pressure was conducted using the
      SphygmoCor (AtCor) device. The composite endpoint of the study was the incidence
      of either death, myocardial infarction, stroke, or admission for symptomatic
      intermittent claudication or decompensated congestive heart failure. RESULTS:
      Fifteen patients (23%) reached the composite endpoint during a follow-up of 4.4
      years. Binary logistic regression using PWV, AI75, central aortic systolic
      pressure, peripheral systolic pressure, and pulse pressure as covariates revealed
      that PWV was significantly associated with cardiovascular events (10.1 +/- 3.6
      m/s in subjects reaching the endpoint vs 8.5 +/- 1.5 m/s in subjects not reaching
      the endpoint; P = .048). CONCLUSION: Increased arterial stiffness as assessed by
      PWV predicts CVE in renal transplant recipients and may be regarded as a
      footprint of accelerated arteriosclerosis for those patients.

PMID- 25769580
TI  - Efficacy of intravenous immunoglobulin in the treatment of persistent BK viremia
      and BK virus nephropathy in renal transplant recipients.
AB  - BK virus-associated nephropathy (BKVN) can cause clinically significant viral
      infection in renal transplant recipients, leading to allograft dysfunction and
      loss. The usual management of BKVN involves the reduction of immunosuppression
      and the addition of leflunomide, quinolones, and cidofovir, but the rate of graft
      loss remains high. The aim of this study was to assess the impact of treatment
      with intravenous human immunoglobulin (IVIG) on the outcome of BKVN in renal
      transplant recipients. Upon diagnosis of BKVN, patients remained on anti
      polyomavirus treatment, consisting of the reduction of immunosuppression and the
      use of leflunomide therapy. Treatment with IVIG was given only to patients who
      did not respond to 8 weeks of the adjustment of immunosuppression and
      leflunomide. All 30 patients had persistent BKV viremia and BKVN with their mean
      BK viral loads higher than the baseline (range, 15,000-2 million copies/mL). Mean
      peak BK load was 205,314 copies/mL compared with 697 copies/mL after 1 year of
      follow-up. Twenty-seven patients (90%) had a positive response in clearing
      viremia. The actuarial patient and graft survival rates after 12 months were 100%
      and 96.7%, respectively. IVIG administration appeared to be safe and effective in
      treating BKV viremia and BKVN and preventing graft loss in patients who had
      inadequate response to immunosuppression reduction and leflunomide therapy. 

PMID- 25769582
TI  - Radioembolization using yttrium-90 microspheres as bridging and downstaging
      treatment for unresectable hepatocellular carcinoma before liver transplantation:
      initial single-center experience.
AB  - INTRODUCTION: HCC is the sixth most common malignancy worldwide and is the third
      most common cause of cancer related mortality. Moreover, the incidence of HCC is
      increasing. Surgical treatments for HCC including resection and/or
      transplantation provide the best curative outcomes in early stages.
      Unfortunately, many patients present at an advanced stage. Currently,
      locoregional therapies have an emerging role in the management of HCC for
      bridging to liver transplantation and for downstaging the disease to within
      transplant criteria. Radioembolization is among commonly used locoregional
      therapies. OBJECTIVE: To describe our initial experience with the use of
      Therasphere(r) as bridging or downstaging modality before liver transplantation,
      including our institutional indications, technique and outcome. MATERIALS AND
      METHODS: We retrospectively examined our database for liver transplantation after
      the use of Therasphere(r). Nine patients were identified and reported. RESULTS:
      They were 5 females and 4 males. Their current age range is 40-72 years with a
      mean of 53.8 +/- 9.5 years. Three patients had Therasphere(r) as downstaging
      treatment to our institutional transplantation criteria. Our institution is using
      UCSF criteria as a cut off limit for liver transplantation as primary treatment
      modality. The other 6 patients had Therasphere(r) as bridging for liver
      transplantation especially when other modalities are not possible. None of these
      lesions were treated by any other locoregional treatment before or after
      Therasphere(r). Follow-up after liver transplantation ranged between 3.7 and 60.1
      months (mean of 15.8 +/- 17.7 months). All patients are still living, no
      retransplantation was done and none of them showed evidence of disease recurrence
      (100% graft, patient and disease free survival). CONCLUSION: Our initial
      experience showed that Therasphere(r) is a promising therapeutic tool for both
      downstaging and bridging of HCC before liver transplant.

PMID- 25769581
TI  - Clinical utility of hepatic-perfusion computerized tomography in living-donor
      liver transplantation: a preliminary study.
AB  - BACKGROUND: Vascular complications are a primary diagnostic consideration in
      liver transplant recipients, with an overall incidence of 9%. Cross-sectional
      imaging techniques provide information regarding vascular structure and luminal
      patency but can not quantitatively assess hepatocyte damage in the liver graft
      parenchyma. Perfusion computerized tomography (CT) is a recently developed method
      that allows for quantitative evaluation of hemodynamic changes in tissue. Our
      objective was to evaluate the clinical utility of perfusion CT in assessing
      vascular complications during living-donor liver transplantation (LDLT). METHODS:
      The 33 recipients were divided into 3 groups according to Doppler
      ultrasonographic findings: hepatic arterial complication group, portal venous
      complication group, and hepatic venous complication group. Blood volume (BV),
      blood flow (BF), arterial liver perfusion (ALP), portal venous perfusion (PVP),
      and hepatic perfusion index (HPI) were calculated for the affected vascular
      territory regions. RESULTS: Compared with normal liver parenchyma, BV, BF, ALP,
      and HPI were significantly lower in the hepatic arterial complication group.
      Although PVP and BV were significantly lower, ALP, HPI, and BF were higher in the
      affected vascular territory region than in normal liver parenchyma for the portal
      venous complication group. In the hepatic venous complication group, PVP was
      significantly higher and BF, ALP, and HPI significantly lower in the affected
      vascular territory regions than in normal liver parenchyma. CONCLUSIONS:
      Perfusion CT imaging is a noninvasive technique that enables the quantitative
      evaluation of vascular complications in the graft parenchyma after LDLT and
      permits a quantitative evaluation of the treatment response.

PMID- 25769583
TI  - Clinical therapeutic effects of human umbilical cord-derived mesenchymal stem
      cells transplantation in the treatment of end-stage liver disease.
AB  - We aimed to evaluate clinical therapeutic effects of human umbilical cord-derived
      mesenchymal stem cell (UCMSC) transplantation in the treatment of end-stage liver
      diseases. The human UCMSCs were cultured and prepared, and then transplanted into
      the hepatic tissues of 50 patients with decompensated cirrhosis. The liver
      function, thrombin function, Model for End-Stage Liver Disease (MELD) score, and
      hemodynamic index value were detected during a 24-week follow-up period, with the
      addition of hepatoprotective, antiviral, and other conventional treatments. No
      complications or serious side effects were observed. In the first 2-3 weeks after
      surgery, symptoms including abdominal distension, oliguria, edema, and others
      decreased significantly, with increased appetite compared with before surgery. In
      the 24-week follow-up period, the levels of serum albumin and prealbumin
      increased significantly compared with the preoperative levels; the decrease of
      coagulation indicators was not significant. The MELD scores were also markedly
      increased. Alpha-fetoprotein levels increased without significance after
      treatment. There was no significant difference in the hemodynamic changes in the
      portal and splenic veins according to ultrasound. Moreover, no significant
      differences in the liver and thrombin functions between the hepatitis B virus
      group and the other-etiology group were observed. 

PMID- 25769584
TI  - A novel split liver protocol using the subnormothermic oxygenated circuit system
      in a porcine model of a marginal donor procedure.
AB  - BACKGROUND: A merit of subnormothermic perfusion has been reported to preserve
      grafts from ischemic injury in animal models. The split liver technique is
      commonly performed to solve the shortage of liver grafts. However, there has been
      no study showing the effect of a split liver graft on subnormothermic perfusion.
      We herein investigated the split liver protocol using a subnormothermic
      oxygenated circuit system (SOCS). METHODS: Auxiliary liver transplantation was
      performed in a porcine marginal donor model by using a SOCS. In the SOCS group,
      the portal vein and hepatic artery of the graft were cannulated, and the graft
      was perfused by SOCS. In the cold storage (CS) group, the graft was placed in
      cold preservation solution. In the preservation phase, the graft was split.
      RESULTS: There were no significant differences in the biochemical markers between
      the SOCS and CS groups. In terms of the histology, the sinusoidal spaces were
      widened in the CS group 12 hours after implantation. CONCLUSION: We have
      demonstrated a possibility to use SOCS with the split liver protocol by using a
      porcine model. This split liver protocol using SOCS will extend the split liver
      criteria and rescue more patients from hepatic failure, including pediatric
      patients.

PMID- 25769585
TI  - Living donor liver transplantation: a life-saving option in emergency situations
      for diffuse hepatic neuroendocrine tumor metastasis.
AB  - Liver metastasis is the main cause of death in patients with
      gastroenteropancreatic neuroendocrine tumors (GEP-NETs), but only 10%-20% of
      metastasis in these cases is resectable at the time of diagnosis. In some cases,
      medical and interventional radiological treatments may not be effective. Liver
      transplantation, although controversial, may be an option. Worldwide organ
      sharing systems do not provide exception points, but give recommendations for
      liver transplantation in cases of hepatic metastasis from GEP-NETs due to the
      issue of fair access to donor organs. Living donor liver transplantation is an
      option in select cases. Presented here are 2 cases in which living donor liver
      transplantation was performed in emergency situations as a life-saving procedure,
      with acceptable survival and without donor complications. 

PMID- 25769586
TI  - Prediction of gross post-transplant outcomes based on the intra-operative decline
      in C-reactive protein in living donor liver transplantation.
AB  - BACKGROUND: C-reactive protein (CRP), a marker of infection and inflammation, is
      produced mainly in the liver. Its slow onset and various influencing factors have
      limited studies on the intra-operative changes in CRP in living donor liver
      transplantation (LDLT). In this study, we asked whether the intra-operative
      changes in CRP predicts post-transplant outcome. METHODS: The peri-transplant
      data of 263 LDLT patients were reviewed. "Intra-operative CRP decline" was
      calculated by subtracting the pretransplant CRP from the 1-day post-transplant
      CRP. A negative value defined an intra-operative decline. Peri-transplant
      variables were compared between patients with and without gross post-transplant
      outcomes (GPOs), including death, allograft dysfunction, infection, and kidney
      injury. Multivariate logistic regression was used to develop a model to predict
      GPO, and area receiver operating characteristic curve (AUC) analysis was used to
      evaluate the prognostic accuracies for GPO. RESULTS: GPOs were determined in 95
      LDLT patients (36.1%). GPO-positive patients had a lesser change in CRP levels
      (0.51 versus 1.16 mg/dL) and a higher incidence of a decline in CRP (34.7% versus
      13.7%) during LDLT (P < .05) than did GPO-negative patients. The AUC of the intra
      operative CRP change (0.585; P = .018) did not significantly differ from that of
      the pretransplant CRP. After multivariate adjustment, a patient with an intra
      operative decline in CRP had a 3.21-fold higher risk for GPO occurrence (P =
      .001). CONCLUSIONS: GPO occurrence was related to the intra-operative decline of
      CRP in LDLT patients. However, multivariate compensation might be required for
      the clinical utilization of intra-operative decline in CRP as a prognostic
      indicator.

PMID- 25769587
TI  - Milan criteria, University of California, San Francisco, criteria, and model for
      end-stage liver disease score as predictors of salvage liver transplantation.
AB  - The selection criteria for salvage liver transplantation (SLT) candidates have
      not been previously established. A global analysis for the association between
      the criteria and prognosis is required. All of the adult patients who underwent
      liver transplantation with a diagnosis of hepatocellular carcinoma (HCC) from
      January 1, 2000, to December 31, 2011, were retrospectively analyzed. A total of
      1,554 cases were involved, including 1,392 primary liver transplantation (PLT)
      and 162 SLT cases. All the cases were classified into 3 groups according to the
      Milan criteria combined with the University of California, San Francisco (UCSF),
      criteria, and significant differences were found between the 2 groups. The
      overall graft survival rate was lower in all cases of SLT than in PLT (P = .030).
      Within the Milan criteria, no significant difference in the graft survival rate
      was found between PLT and SLT. In a Cox regression analysis, the Model for End
      Stage Liver Disease (MELD) score and tumor levels graded according to the
      Milan/UCSF criteria were found to be independent risk factors for the graft
      survival rate. Receiver operating characteristic (ROC) curves were generated by
      the fatality risk values calculated by means of the Cox model and the 1-year
      graft survival rates of all the patients and of the SLT patients. The areas under
      the ROC curves were 0.922 and 0.935, respectively. Compared with PLT, the global
      graft survival rate of SLT was compromised. The MELD score and Milan/UCSF
      criteria were effective in predicting the prognosis of PLT and SLT. Therefore,
      when the recurrent lesions of HCC are within the Milan criteria, SLT can be
      performed with a good prognosis.

PMID- 25769588
TI  - Prevalence of hypertension after living-donor liver transplantation: a
      prospective study.
AB  - BACKGROUND: Hypertension is common among patients who have undergone liver
      transplantation and is a major contributor to cardiovascular events. Few studies
      have studied the risk factors associated with post-liver transplantation (LT)
      hypertension. This prospective study assessed the prevalence of post-LT
      hypertension and associated preoperative risk factors. METHODS: From May 2008 to
      December 2009, 79 normotensive adult patients (>= 18 years old) who underwent
      living-donor LT with a median follow up of 4.79 +/- 0.88 years were enrolled.
      Patients' pre-LT demographics, clinical data, pre-LT diabetes, and
      immunosuppressive agents used after LT were studied for their association with
      post-LT hypertension. RESULTS: The prevalence of post-LT hypertension was 49.4%.
      The independent risk factors for post-living-donor LT hypertension were pre-LT
      systolic blood pressure (SBP; odds ratio [OR], 1.04; 95% confidence interval
      [CI], 1.00-1.09; P = .039) and post-LT administration of mammalian target of
      rapamycin (mTOR) inhibitors (OR, 4.08; 95% CI, 1.40-11.94; P = .010). Pre-LT
      diabetes had a negative predictive value (OR, 0.15; 95% CI, 0.03-0.74; P = .019).
      Neither age, male sex, smoking, pre-LT serum cholesterol and triglyceride levels,
      tacrolimus, nor glucocorticoid was associated with post-LT hypertension.
      CONCLUSIONS: The prevalence of hypertension is high after LT. Higher pre-LT SBP
      and post-LT mTOR inhibitor administration predispose patients to post-LT
      hypertension.

PMID- 25769589
TI  - Efficacy and complications of enteral feeding tube insertion after liver
      transplantation.
AB  - BACKGROUND: Adequate nutritional support for patients undergoing major surgery
      significantly affects postoperative recovery. Data on enteral feeding after liver
      transplantation (LT) are scarce. The aim of this work was to determine the
      efficacy and complications of feeding tubes inserted with the use of fluoroscopic
      assistance, endoscopic assistance, or transperitoneal jejunostomy in patients who
      underwent LT. METHODS: From January 2008 to August 2013, 2,058 LTs were performed
      at Asan Medical Center, Seoul, Korea. Enteral feeding tubes were inserted in 155
      patients (7.5%) after LT: with the use of fluoroscopic placement in 81 (52%),
      endoscopic placement in 49 (32%), and transperitoneal jejunostomy in 25 (16%). We
      retrospectively analyzed the efficacy and complications of enteral feeding tubes.
      RESULTS: The median age was 55 years (interquartile range [IQR] 49-60). Enteral
      feeding indications were a high risk of gastric aspiration (n = 90), gastric
      stasis (n = 27), pneumonia (n = 23), gastrointestinal bleeding (n = 12), and
      bowel rest (n = 3). Median enteral feeding durations were 14.5 days (IQR 8.0
      30.7) for fluoroscopic placement, 20.0 days (IQR 8.0-40.0) for endoscopic
      placement, and 37.5 days (IQR 18.2-86.2) for transperitoneal jejunostomy. Times
      to establishment of oral feeding were 13.0 days (IQR 6.2-25.7) for fluoroscopic
      placement, 24.0 days (IQR 10.5-43.5) for endoscopic placement, and 37.0 days (IQR
      17.0-64.2) for transperitoneal jejunostomy. After tube insertion, tube
      dislocation and blockage occurred in 34 patients (22%) and 16 patients (25%),
      respectively. CONCLUSIONS: Enteral feeding tube insertion in patients who can not
      maintain a nasogastric tube or start oral intake for a long time is important for
      nutritional support after LT. Proper feeding method selection according to
      patient condition can help patients by improving nutritional support after major
      operations such as LT.

PMID- 25769590
TI  - Evaluation of "flat-line" thromboelastography after reperfusion during liver
      transplantation.
AB  - BACKGROUND: "Flat-line" (no clot formation) thromboelastography (TEG) is
      frequently observed after graft reperfusion during liver transplantation (LT). We
      aimed to evaluate the incidence and causes of flat-line TEG after graft
      reperfusion during LT. METHODS: With institutional review board approval, data of
      208 consecutive recipients who underwent LT from May 2010 to May 2012 were
      retrospectively reviewed. We performed 3 different types of TEG measurements at 5
      minutes after graft reperfusion: native TEG (nTEG), tranexamic acid-added TEG
      (tTEG), and protamine-added TEG (pTEG). The flat-line TEG was defined as having
      no trace at all at 60 minutes of TEG. We examined the incidence and causes of
      flat-line nTEG. We also compared recipients with flat-line nTEG (F group) and
      clot-forming nTEG (C group). RESULTS: One hundred eighty-two recipients were
      included in the final analysis. The incidence of flat-line nTEG was 27% (49/182
      cases). Among 49 recipients in the F group, 28 recipients showed clot formation
      in both tTEG and pTEG, 19 recipients in only tTEG, and 1 recipient in only pTEG;
      1 recipient showed no clot formation in any TEGs. Graft from the deceased donor
      was more frequently observed in the F group than in the C group (P = .039). The F
      group showed decreased platelet count (P = .001), increased prothrombin time (P =
      .002), and decreased fibrinogen (P = .009) compared with the C group.
      CONCLUSIONS: No clot formation was relatively common after reperfusion during LT,
      and the main causes were hyperfibrinolysis and heparin effect. Liver graft from
      deceased donors was associated more frequently with no clot formation after
      reperfusion during LT.

PMID- 25769591
TI  - Incidence of cardiovascular and cerebrovascular events associated with sirolimus
      use after liver transplantation.
AB  - BACKGROUND: Sirolimus (SRL) is an immunosuppressant often used in liver
      transplantation (LT) to mitigate renal insufficiency associated with calcineurin
      inhibitors. Sirolimus can cause hyperlipidemia, but its association with coronary
      artery disease (CAD) and cerebrovascular accidents (CVAs) is unclear. The purpose
      of this study was to assess the risk of CAD and CVAs with the use of SRL in LT
      recipients. METHODS: We retrospectively reviewed all of our LT recipients from
      2000 to 2011. Patients with multiorgan transplant, multiple liver transplants,
      everolimus therapy, or survival <3 months were excluded. The 803 remaining
      patients were divided into 3 groups: 1) 134 patients who received and tolerated
      SRL; 2) 604 patients who never received SRL; and 3) 65 patients who started but
      discontinued SRL. The primary outcome was the development of CAD or CVA beyond 4
      months after transplantation with the use of time-dependent Kaplan-Meier
      analysis. RESULTS: In group 1, there were 6 CAD and 2 CVA events; in group 2, 27
      CAD and 16 CVA events; and in group 3, 10 CAD and 2 CVA events. The event-free
      survival for CAD/CVA at 1, 3, and 5 years was 100%, 98.1%, and 97.2% respectively
      for group 1; 99.7%, 98.4%, and 96.1% for group 2; and 92.3%, 92.3%, and 85.6% for
      group 3. On an unadjusted basis, compared with group 2, there was no difference
      in CAD/CVA rates in group 1 (hazard ratio [HR] 0.92; not significant), but there
      was an increase in group 3 (HR 2.94; P = .0019). However, on multivariate
      analysis, only age at transplantation (HR 1.06; P = .001) and diabetes before
      transplantation (P = .011) were associated with increased CAD/CVA risk.
      CONCLUSIONS: Our analysis showed that patients receiving SRL after LT had no
      increased risk of CAD/CVA events compared with patients maintained on a
      calcineurin inhibitor. The risk of CAD/CVA should not be a factor in avoiding
      SRL.

PMID- 25769592
TI  - Serum alkaline phosphatase and bilirubin are early surrogate markers for ischemic
      cholangiopathy and graft failure in liver transplantation from donation after
      circulatory death.
AB  - Liver transplantation with the use of donation after circulatory death (DCD) is
      associated with ischemic cholangiopathy (IC) often leading to graft loss. We
      hypothesized that serial postoperative analysis of alkaline phosphatase and
      bilirubin might identify patients who would later on develop ischemic
      cholangiopathy and/or graft loss, allowing early recognition and potentially
      retransplantation. The University of Washington DCD experience totals 89 DCD
      liver transplantations performed from 2003 to 2011 with Kaplan-Meier estimated 5
      year patient and graft survival rates of 81.6% and 75.6%, respectively; 84/89
      patients transplanted with DCD livers lived >= 60 days after transplantation and
      were analyzed. Serum bilirubin and alkaline phosphatase levels at 1 week, 2 week,
      1 month, and 2 months after transplantation were analyzed. Two-month serum
      bilirubin and alkaline phosphatase proved to have the strongest associations with
      development of IC and graft failure. Two-month alkaline phosphatase of <100 U/L
      had a negative predictive value of 97% for development of IC. Two-month alkaline
      phosphatase demonstrated an inflection starting at >300 U/L strongly associated
      with development of IC (P < .0001). Serum bilirubin at 2 months was most strongly
      associated with graft failure within the 1st year with a strong inflection point
      at 2.5 mg/dL (P = .0001). All jaundiced recipients at 60 days after
      transplantation (bilirubin >2.5 mg/dL) developed graft failure within the 1st
      year (P < .0001). Use of these early surrogate markers could facilitate
      prioritization and early retransplantation for DCD liver recipients with
      allografts destined for failure.

PMID- 25769593
TI  - Comparison of antioxidant effects of isoflurane and propofol in patients
      undergoing donor hepatectomy.
AB  - BACKGROUND: The safety of healthy volunteer donors is one of the most important
      issues in living-donor liver transplantation. Use of the Pringle maneuver during
      donor hepatectomy can result in liver ischemia-reperfusion (IR) injury. The
      objective of this study was to examine the effects of isoflurane and propofol on
      IR injury caused by the Pringle maneuver during donor hepatectomy. METHODS: A
      total of 70 American Society of Anesthesiology I-II donors aged 18-65 years who
      underwent hepatectomy were included in the study. The patients were randomly
      divided into 2 groups: propofol and isoflurane. Plasma superoxide dismutase
      (SOD), malondialdehyde (MDA), total oxidative status (TOS), total antioxidant
      capacity (TAC), and oxidative stress index (OSI) were measured before surgery
      (t0) and after surgery (t1). RESULTS: There were no statistically significant
      differences in demographic features, anesthesia, and times of surgery between the
      groups (P > .05). Plasma TAC levels at t0 and t1 were significantly lower in the
      propofol group than in the isoflurane group (P < .05). OSI at t1 was
      significantly higher in the propofol group than in the isoflurane group (P <
      .05). MDA levels were significantly higher in the propofol group than in the
      isoflurane group at t0 (P < .05). MDA levels level were significantly higher in
      the isoflurane group than in the propofol group at t1 (P < .05). CONCLUSIONS:
      Propofol may have protective effects against IR injury caused by the Pringle
      maneuver during donor hepatectomy in living-donor transplantations. However, the
      effectiveness of propofol for clinical use needs to be investigated further.

PMID- 25769594
TI  - MDCT evaluation of early pulmonary infection types after liver transplantation.
AB  - INTRODUCTION: Opportunistic pulmonary infections frequently occur after liver
      transplantation, and affect mortality and morbidity significantly. The purpose of
      this study was to define the incidence, types, and imaging characteristics of
      pulmonary infections in liver transplant recipients with multidetector CT (MDCT)
      evaluation. METHODS: Thirty-five adult transplant recipients diagnosed with a
      pulmonary infection within the first 45 days posttransplantation were reviewed
      retrospectively from March 2002 to December 2013. MDCT features were evaluated
      retrospectively by 2 radiologists in consensus. All diagnoses were made by sputum
      analysis, cultures, biopsies, and postmortem histopathologic evaluation. RESULTS:
      Pneumococcus pneumonia was found in 7 patients. Five patients had nonspecific
      pneumonia, Candidiasis, Klebsiella, and Aspergillosis separately. S aureus
      pneumonia was detected in 2 patients and the other 2 patients had Escherichia
      coli pneumonia. Two patients had active tuberculosis and 1 patient had
      Acinetobacter pneumonia also. Four main MDCT patterns were identified: patchy
      infiltrations (10%), tree-in-bud pattern (9.5%), ground-glass opacity (8.5%), and
      nodules with halo sign (6%). One patient had a cavitary lesion owing to
      tuberculosis. CONCLUSION: Although the incidence of pulmonary complications in
      liver recipients was relatively low, mortality from serious infections was high.
      Care must be taken with pulmonary infectious complications in the posttransplant
      period. For any suspicious case, MDCT evaluation for specific patterns of early
      accurate diagnosis is very important.

PMID- 25769595
TI  - Limited hepatitis B immunoglobulin with potent nucleos(t)ide analogue is a cost
      effective prophylaxis against hepatitis B virus after liver transplantation.
AB  - BACKGROUND: Prophylaxis against hepatitis B virus (HBV) recurrence after
      orthotopic liver transplantation (OLT) includes lifelong hepatitis B
      immunoglobulin (HBIG) and oral antiviral agent(s). In the presence of high
      genetic-barrier nucleos(t)ide analogues, the need for lifelong HBIG is
      questioned. We evaluated the safety and cost-effectiveness of a limited HBIG
      course. METHODS: OLT from 2006 to 2013 were reviewed. Patients with pre-OLT
      hepatitis B virus surface antigen who received HBV prophylaxis with 2 HBIG doses
      (anhepatic and first post-operative day; 10,000 units/dose) and potent
      nucleos(t)ide analogues were included. The primary end point was HBV recurrence
      (HBV-DNA detection). RESULTS: Thirteen patients (primary transplants) were
      included, median Model for End-Stage Liver Disease score was 18, and there was no
      fulminant failure; HBV-DNA was detected in 4 patients at OLT. After OLT, 10
      patients received entecavir and/or tenofovir. Median follow-up was 23 months. One
      recurrence occurred (7.7%) at month 13 (HBV-DNA: 14 IU/mL); the graft maintained
      excellent function. This minimal viremic expression is related to hepatocellular
      carcinoma recurrence with neoplastic replication carrying integrated HBV-DNA;
      thus, there is no defined HBV viral recurrence. No graft loss or patient death
      was related to HBV recurrence. The 1-year patient and graft survival rate was
      84.6%. Cost-savings in the first year was $178,100 per patient when compared with
      Food and Drug Administration-approved HBIG dosing. CONCLUSIONS: In the era of
      potent oral nucleos(t)ide analogues, a limited HBIG course appears to be cost
      effective in preventing HBV recurrence.

PMID- 25769596
TI  - Prior sternotomy increases the mortality and morbidity of adult heart
      transplantation.
AB  - BACKGROUND: This study investigated the effect of prior sternotomy (PS) on the
      postoperative mortality and morbidity after orthotopic heart transplantation
      (HTx). METHODS: Of 704 adults who underwent HTx from December 1988 to June 2012
      at a single institution, 345 had no PS (NPS group) and 359 had >= 1 PS (PS
      group). Survival, intraoperative use of blood products, intensive care unit (ICU)
      and hospital stays, frequency of reoperation for bleeding, dialysis, and >48-hour
      ventilation were examined. RESULTS: The NPS and PS groups had similar 60-day
      survival rates (97.1 +/- 0.9% vs 95.3 +/- 1.1%; P = .20). However, the 1-year
      survival was higher in the NPS group (94.7 +/- 1.2% vs 89.7 +/- 1.6%; hazard
      ratio [HR], 1.98; 95% CI, 1.12-3.49; P = .016). The PS group had longer pump time
      and more intraoperative blood use (P < .0001 for both). Postoperatively, the PS
      group had longer ICU and hospital stays, and higher frequencies of reoperation
      for bleeding and >48-hour ventilation (P < .05 for all comparisons). Patients
      with 1 PS (1PS group) had a higher 60-day survival rate than those with >= 2 PS
      (2+PS group; 96.7 +/- 1.1% vs 91.1 +/- 3.0%; HR, 2.70; 95% CI, 1.04-7.01; P =
      .033). The 2+PS group had longer pump time and higher frequency of postoperative
      dialysis (P < .05 for both). Patients with prior VAD had lower 60-day (91.1 +/-
      3.0% vs 97.1 +/- 0.9%; P = .010) and 1-year (87.4 +/- 3.6% vs 94.7 +/- 1.2%; P =
      .012) survival rates than NPS group patients. Patients with prior CABG had a
      lower 1-year survival than NPS group patients (89.0 +/- 2.3% vs 94.7 +/- 1.2%; P
      = .018). CONCLUSION: The PS group had lower 1-year survival and higher
      intraoperative blood use, postoperative length of ICU and hospital stays, and
      frequency of reoperation for bleeding than the NPS group. Prior sternotomy
      increases morbidity and mortality after HTx.

PMID- 25769597
TI  - New predictive equation for lung volume using chest computed tomography for size
      matching in lung transplantation.
AB  - PURPOSE: Lung size matching is important in lung transplantation (LT). With
      advances in computed tomography (CT) technology, multidetector row CT can
      accurately measure the thoracic cage and lung volumes. The objective of this
      study was to generate a new regression equation using demographic data based on
      the measured CT lung volume in a healthy population to predict the CT lung volume
      of the donor in LT size matching. MATERIALS AND METHODS: The medical records of
      healthy subjects who underwent chest CT scans to screen for lung cancer were
      retrospectively reviewed. CT lung volume was semi-automatically measured using a
      threshold-based auto-segmentation technique. New regression equations for CT lung
      volume were generated by multiple linear regression analysis using demographic
      data including height (H, cm), weight (W, kg), and age (A, years). The percentage
      error rate (%) of the equations were calculated as ([Estimated CT lung volume-
      Measured CT lung volume]/Measured CT lung volume * 100). A percentage error rate
      within +/- 20% was considered acceptable. RESULTS: A total of 141 men aged 27 to
      55 years (mean, 46.7 +/- 6.2 years) and 128 women aged 20 to 55 years (mean, 45.4
      +/- 7.2 years) were enrolled. The final regression equations for CT lung volume
      were (-5.890 + 0.067 H - 0.030 W + 0.020 A) in men and (-6.698 + 0.072 H - 0.024
      W) in women. The mean absolute error rate was 10.9 +/- 9.0% and 11.0 +/- 8.5% in
      men and women, respectively. Percentage error rates were within +/- 20% in 121 of
      141 (85.8%) men and 113 of 128 (88.3%) women. CONCLUSION: These equations could
      predict the CT lung volume of healthy subjects using demographic data. Using
      these equations, the predicted CT lung volume of donors could be matched to the
      measured CT lung volume of recipients in lung transplantation.

PMID- 25769598
TI  - Usefulness of high-sensitivity troponin I for the monitoring of subclinical acute
      cellular rejection after cardiac transplantation.
AB  - BACKGROUND: There are conflicting data about the role of cardiac troponin I
      (cTnI) as determined by means of conventional methods for the prediction of acute
      rejection after heart transplantation (HT). The purpose of this study was to
      evaluate whether cTnI as measured by means of the early prototype high
      sensitivity assay (hs-cTnI) can predict acute rejection episode after HT compared
      with grade of rejection in endomyocardial biopsy (EMB). METHODS: This was a
      single-center cross-sectional study evaluating cTnI levels with the use of both
      hs-cTnI and current less sensitive conventional cTnI (conv-cTnI) assays measured
      at the time of EMB after HT. We calculated an index ratio of observed cTnI to
      expected mean cTnI for each individual patient defined as the mean cTnI
      measurements at EMB 60 days after HT. RESULTS: A total of 252 biopsies from 47
      patients were included in this study. In the multivariable mixed model analysis
      in relation to the presence of acute rejection 60 days after HT, hs-cTnI level
      was significantly related to the presence of rejection (P = .010). The hs-cTnI
      ratio index was significantly higher at the time of rejection (median, 1.37;
      interquartile range [IQR], 1.23-2.88) compared with those without rejection
      (median, 0.90; IQR, 0.51-1.16; P < .001). In receiver operating characteristic
      curve analysis, an hs-cTnI ratio index of >=1.17 could predict the acute
      rejection with a sensitivity of 82.4% and a specificity of 77.1%. CONCLUSIONS: An
      increased hs-cTnI ratio index was significantly related to rejection episodes.
      Serial monitoring of hs-cTnI and comparing it with the values without rejection
      might be useful for the detection of acute rejection after HT.

PMID- 25769599
TI  - Importance of early absolute lymphocyte count after allogeneic stem cell
      transplantation: a retrospective study.
AB  - INTRODUCTION: Early lymphocyte recovery after allogeneic hematopoietic stem cell
      transplantation (HSCT) is related to the prevention of serious infections and the
      clearing of residual tumor cells. METHODS: We analyzed the absolute lymphocyte
      count at 20 (D+20) and 30 (D+30) days after HSCT in 100 patients with malignant
      hematologic diseases and correlated with the risk of transplant-related
      mortality, overall survival (OS), disease-free survival (DFS), nonrelapsed
      mortality (NRM), and risk of infection. RESULTS: Patients presenting with
      lymphocyte counts of <300 * 103/MUL on D+30 have a 3.76 times greater risk of
      death in <100 days. Over a medium follow-up of 20 months OS, DFS, and NRM were
      similar between the groups. CONCLUSION: In our group of patients delayed
      lymphocyte recovery after HSCT was a predictor of early death post-HSCT.

PMID- 25769600
TI  - Rituximab after autologous stem cell transplantation enhances survival of B-cell
      lymphoma patients: a meta-analysis and systematic review.
AB  - BACKGROUND: Numerous studies have demonstrated the efficacy of rituximab before
      autologous stem cell transplantation (ASCT) for the treatment of B-cell non
      Hodgkin lymphoma, but the few studies on rituximab treatment after ASCT have not
      established conclusively the clinical benefits of this particular treatment
      regimen. PATIENTS AND METHODS: We conducted a metaanalysis of 3 comparative
      studies encompassing 407 lymphoma patients treated with rituximab after ASCT.
      RESULTS: Combined results revealed a significantly higher event-free survival
      (EFS) in the rituximab-treated (R+) group compared with the R- group (P = .003 at
      1 year; P = .03 at 3 years; P = .001 at 4 years). Moreover, the R+ group also
      demonstrated higher overall survival (OS) and complete remission (CR) rates (P =
      .0006 and P < .0001, respectively, at 1 year) without a significant increase in
      adverse events. CONCLUSIONS: According to the included articles, there were no
      differences in CR, overall response, 3-year EFS, or 3-year OS between rituximab
      naive patients and patients previously treated with rituximab before ASCT. Post
      ASCT maintenance regimens including rituximab show increased EFS, OS, and CR.

PMID- 25769601
TI  - Febrile neutropenic infection occurred in cancer patients undergoing autologous
      peripheral blood stem cell transplantation.
AB  - OBJECTIVE: The objective of this study was to investigate the incidence, risk
      factors, and clinical and prognostic characteristics of febrile infection that
      occurred during the neutropenic period in cancer patients who underwent
      autologous peripheral blood stem cell transplantation (APBSCT). METHODS: Clinical
      data of all the APBSCT cases from 2007 to 2009 in Sun Yat-sen University Cancer
      Center were collected and retrospectively analyzed. RESULTS: Eighty-nine APBSCT
      subjects were investigated. Neutropenia usually occurred on the 4th day (range, 0
      15) after transplantation and lasted 6 (range, 3-27) days. Febrile neutropenia
      occurred in 78.7% patients and lasted around 3 (range, 1-20) days and no
      infection-related deaths were observed. For febrile episodes, 12 patients (17.1%)
      were diagnosed as having microbiologically documented infections (MDI). Initial
      empirical antimicrobial therapy was given to all cases of post-APBSCT febrile
      neutropenia, of which 44 cases (62.9%) were effective. Febrile neutropenia
      occurred in 25/34 (73.5%) patients who were given antifungal drugs for
      prophylaxis. CONCLUSIONS: Neutropenic infection is still the major complication
      in APBSCT patients and duration of neutropenia is one of the major risk factors.
      Prophylactic administration of antifungal drugs seems to be invalid to reduce
      post-APBSCT infection. Sufficient doses of broad-spectrum antibiotics at the
      early stage lead to better results of initial antimicrobial treatment.

PMID- 25769602
TI  - Corneal transplantation activity over 7 years: changing trends for indications,
      patient demographics and surgical techniques from the Corneal Transplant
      Epidemiological Study (CORTES).
AB  - This study aims to examine evolving indications and changing trends for corneal
      transplantation in Italy. Corneal transplantations performed with donor tissues
      distributed by the Veneto Eye Bank Foundation between 2002 and 2008 were
      prospectively evaluated. Of the 13,173 keratoplasties performed on 11,337
      patients, 10,742 (81.5%) were penetrating (PK), 1644 (12.5%) were anterior
      lamellar (ALK), and 787 (6.0%) were endothelial (EK). Keratoconus (42.5%),
      regraft (18.9%), and pseudophakic bullous keratopathy (PBK, 11.9%) were the
      leading indications for PK, with keratoconus (69.6%) and regraft (6.5%) showing
      higher indications for ALK, whereas pseudophakic bullous keratopathy (50.1%) and
      regraft (18.7%) were the major indications for EK. There was an overall decrease
      observed in corneal grafting for keratoconus (P = .0048) and an increase for PBK
      (P = .0653) and regrafting (P = .0137). These indications differed by age and
      gender. The number of keratoplasties over 7 years was stable (P = .2394),
      although the annual number of PKs declined by 34.0% (P = .0250), ALKs began to
      rise from 2005 (P = .0600), whereas EKs showed a huge growth, with their number
      tripling in 2007 and further doubling in 2008 (P = .0004). Leading indications
      for keratoplasty showed similar data that have been reported elsewhere for
      Western countries over the past few decades, albeit with a higher percentage of
      keratoconus. However, the overall number of keratoplasties for keratoconus was in
      decline, whereas regraft keratopathy and PKs increased due to the application of
      the newer surgical techniques for corneal grafting. This highlights an important
      shift in managing corneal diseases toward the application of selective and more
      conservative surgeries and changes in indications in corneal transplantation.

PMID- 25769603
TI  - Coconut water solutions for the preservation of spleen, ovary, and skin
      autotransplants in rats.
AB  - BACKGROUND: The purpose of this study was to evaluate the efficacy of coconut
      water in the preservation of spleen, ovary, and skin autotransplantations in
      rats. METHODS: Fifty female Wistar rats were divided randomly into 5 groups on
      the basis of the following tissue graft preservation solutions: group 1, lactated
      Ringer's; group 2, Belzer's solution; group 3, mature coconut water; group 4,
      green coconut water; and group 5, modified green coconut water. In group 5, the
      green coconut water solution was modified to obtain the same electrolyte
      composition as Belzer's solution. The spleen, ovaries, and a skin fragment were
      removed from each animal, stored for 6 hours in one of the solutions, and then re
      implanted. The recoveries of tissue functions were assessed 90 days after surgery
      by means of spleen scintigraphy and blood tests. The implanted tissues were
      collected for histological analyses. RESULTS: Higher immunoglobulin G levels were
      observed in the animals of group 5 than in the animals of group 1. Differences in
      follicle-stimulating hormone levels were observed between groups 1 and 2 (P <
      .001), between groups 4 and 2 (P = .03), and between groups 5 and 2 (P = .01).
      The spleen scintigraphy results did not differ among the groups. The ovarian
      tissue was better preserved in the mature coconut water group (P < .007).
      CONCLUSIONS: Solutions containing coconut water allowed for the preservation of
      the spleen, ovaries, and skin for 6 hours, and the normal functions of these
      tissues were maintained in rats.

PMID- 25769604
TI  - The effect of Asarinin on Toll-like pathway in rats after cardiac allograft
      implantation.
AB  - OBJECTIVE: The objective of this study was to study the mechanism of the anti
      rejection effect of Asarinin in rats that underwent cardiac allograft
      implantation. METHODS: Hearts from Wistar rats were transplanted into the
      abdominal cavity of Sprague Dawley rats (SD rats) 64 SD rats received either
      cyclosporin A (CsA), Asarinin, or demi-dose of cyclosporine A and Asarinin
      through oral administration. On the seventh day post-transplantation, the
      expression of Toll-like receptor 4 (TLR4), chemokine (C-X-C motif) receptor 3
      (CXCR3) in myocardium, and the level of interleukin (IL)-12 in the peripheral
      blood were analyzed 7 days after transplantation. RESULTS: The survival time in 3
      groups (CsA group, Asarinin group, and semi-dose CsA group) prolonged (P < .01),
      the microscope myocardial histopathology in 3 groups (CsA group, Asarinin group
      and semi-dose CsA group) relieved, the expression of TLR4 and CXCR3 in 3 groups
      was significantly decreased (P < .01) when compared with the control group. The
      level of IL-12 decreased remarkably (P < .05) in the 3 groups when compared with
      the control group. CONCLUSIONS: The combined data suggested that Asarinin
      decreased peripheral blood concentration of IL-12 and inhibited the expression of
      TLR4 and CXCR3, which means Asarinin may have a role on TLR4 pathway and produced
      prolongation of allograft heart survival.

PMID- 25769605
TI  - A rat model designed for the continuous intraarterial infusion of cyclosporine.
AB  - BACKGROUND: Limb allotransplantation is not a life-saving treatment. However,
      large doses of immunosuppressive agents are needed. There is an urgent need to
      increase the selectivity and targeting of drugs. METHODS: We designed a rat model
      for intraarterial infusion of cyclosporine (CSA) based on the hindlimb replanted
      model to simulate the limb allotransplantation. To investigate whether
      intraartery infusion could improve the drug's distribution, we infused CSA 4.0
      mg/kg per day continuously into either the superficial epigastric artery (IA
      group) or superficial epigastric vein (IV group) of Lewis rats. RESULTS: On day
      10, CSA concentrations were measured in skin, muscle, and bone tissues of
      hindlimb. Samples were taken from different parts of the bilateral hindlimbs in
      the IA group and right hindlimb only in the IV group. Tissue concentrations of
      the perfusion side were much higher in IA group. Systemic concentrations of IA
      group were higher than IV group. CONCLUSIONS: These results warrant further
      research in our next limb allotransplantation model.

PMID- 25769606
TI  - Acquiring Kupffer cells in mice using a MACS-based method.
AB  - OBJECTIVE: This study sought to establish a new method to isolate Kupffer cells
      (KCs) by magnetic activated cell sorting (MACS). METHODS: Nonparenchymal cells
      were acquired from C57BL/6 mice livers by a perfusion system in vivo and then
      stained with F4/80(+) fluorescein isothiocyanate and CD11c(-) phycoerythrin
      antibodies. After incubating with immunomagnetic beads, F4/80(+)CD11c(-) KCs were
      obtained by MACS selection. The purity was evaluated by flow cytometry, and the
      morphological features and vitality were analyzed in in vitro cultures. RESULTS:
      Compared with traditional methods, acquiring KCs by MACS was characterized by
      economy, efficiency, and high purity. The F4/80(+)CD11c(-) KCs cultured in vitro
      also showed the typical adherent shape and excellent phagocytic ability.
      CONCLUSIONS: With the 2-step method using immunomagnetic beads, we provide a new
      method by which KCs can be obtained from mouse liver with high purity and
      distinct phenotype of F4/80(+) CD.

PMID- 25769607
TI  - The role of the killer cell immunoglobulin-like receptor (KIR) "missing self"
      model in unrelated donor HSCT: a meta-analysis.
AB  - Some studies have found that donor-recipient killer cell immunoglobulin g-like
      receptor (KIRs) ligand compatibility or incompatibility influences the prognosis
      of hematopoietic stem cell transplantation between unrelated individuals,
      although the conclusions of these studies are controversial. We performed a meta
      analysis concerning unrelated donor transplantation with donor-recipient KIRs
      compatible or incompatible. A higher 5-year overall survival rate (odds ratio
      [OR] = 1.93, 95% confidence interval [CI] = 1.03 to 3.61, P = .04) was found in
      KIR-mismatched transplantations; however, no difference was observed in the
      incidence of grade 2 to 4 acute graft-vs-host disease (OR = 0.94, 95% CI = 0.71
      to 1.24, P = .64), 5-year relapse rate (OR = 1.05, CI = 0.75 to 1.47, P = .77),
      or transplantation/treatment-related mortality (OR = 0.61, CI = 0.15 to 2.51, P =
      .50). Our meta-analysis confirmed that incompatibility in KIR ligands favors 5
      year overall survival rate but has no effect on the incidence of grade 2 to 4
      acute graft-vs-host disease, relapse, or transplantation/treatment-related
      mortality.

PMID- 25769608
TI  - Ginsenoside Rg1 protects chronic cyclosporin a nephropathy from tubular cell
      apoptosis by inhibiting endoplasmic reticulum stress in rats.
AB  - INTRODUCTION: This study tested the effect of ginsenoside Rg1 (G-Rg1) in
      cyclosporin A (CsA)-induced endoplasmic reticulum (ER) stress on renal tubular
      cell apoptosis in a rat model of chronic CsA nephropathy. MATERIALS AND METHODS:
      Twenty-two Sprague-Dawley rats were randomized into 3 groups: a control group, a
      model group (CsA 25 mg/kg per day), and a G-Rg1 treatment group (CsA 25 mg/kg per
      day and G-Rg1 20 mg/kg per day). We examined the effects of G-Rg1 on
      histopathology, terminal deoxynucleotidyl transferase dUTP nick-end labeling
      staining, and expression of glucose-regulated protein 78, CCAAT/enhancer-binding
      protein homologous protein, and caspase-3 by using Western blot analysis.
      RESULTS: G-Rg1 attenuated CsA-induced tubulointerstitial fibrosis and reduced
      tubular epithelial cell apoptosis as assessed by terminal deoxynucleotidyl
      transferase dUTP nick-end labeling staining and caspase-3 expression. Compared
      with the model group, it reduced the expression of glucose-regulated protein 78
      and CCAAT/enhancer-binding protein homologous protein (0.12 +/- 0.03 vs 0.48 +/-
      0.05 [P < .01]; 0.55 +/- 0.11 vs 1.08 +/- 0.07 [P < .05]), respectively.
      CONCLUSIONS: G-Rg1 mitigates the progression of chronic CsA nephropathy, at least
      in part, through inhibition of ER stress-triggered tubular cell apoptosis.

PMID- 25769609
TI  - Transcription factor Foxo1 is a negative regulator of natural killer cell
      maturation and function.
AB  - Little is known about the role of negative regulators in controlling natural
      killer (NK) cell development and effector functions. Foxo1 is a multifunctional
      transcription factor of the forkhead family. Using a mouse model of conditional
      deletion in NK cells, we found that Foxo1 negatively controlled NK cell
      differentiation and function. Immature NK cells expressed abundant Foxo1 and
      little Tbx21 relative to mature NK cells, but these two transcription factors
      reversed their expression as NK cells proceeded through development. Foxo1
      promoted NK cell homing to lymph nodes by upregulating CD62L expression and
      inhibited late-stage maturation and effector functions by repressing Tbx21
      expression. Loss of Foxo1 rescued the defect in late-stage NK cell maturation in
      heterozygous Tbx21(+/-) mice. Collectively, our data reveal a regulatory pathway
      by which the negative regulator Foxo1 and the positive regulator Tbx21 play
      opposing roles in controlling NK cell development and effector functions. 

PMID- 25769610
TI  - Retinoic acid is essential for Th1 cell lineage stability and prevents transition
      to a Th17 cell program.
AB  - CD4(+) T cells differentiate into phenotypically distinct T helper cells upon
      antigenic stimulation. Regulation of plasticity between these CD4(+) T-cell
      lineages is critical for immune homeostasis and prevention of autoimmune disease.
      However, the factors that regulate lineage stability are largely unknown. Here we
      investigate a role for retinoic acid (RA) in the regulation of lineage stability
      using T helper 1 (Th1) cells, traditionally considered the most phenotypically
      stable Th subset. We found that RA, through its receptor RARalpha, sustains
      stable expression of Th1 lineage specifying genes, as well as repressing genes
      that instruct Th17-cell fate. RA signaling is essential for limiting Th1-cell
      conversion into Th17 effectors and for preventing pathogenic Th17 responses in
      vivo. Our study identifies RA-RARalpha as a key component of the regulatory
      network governing maintenance and plasticity of Th1-cell fate and defines an
      additional pathway for the development of Th17 cells.

PMID- 25769611
TI  - Regulatory T cell reprogramming toward a Th2-cell-like lineage impairs oral
      tolerance and promotes food allergy.
AB  - Oral immunotherapy has had limited success in establishing tolerance in food
      allergy, reflecting failure to elicit an effective regulatory T (Treg) cell
      response. We show that disease-susceptible (Il4ra(F709)) mice with enhanced
      interleukin-4 receptor (IL-4R) signaling exhibited STAT6-dependent impaired
      generation and function of mucosal allergen-specific Treg cells. This failure was
      associated with the acquisition by Treg cells of a T helper 2 (Th2)-cell-like
      phenotype, also found in peripheral-blood allergen-specific Treg cells of food
      allergic children. Selective augmentation of IL-4R signaling in Treg cells
      induced their reprogramming into Th2-like cells and disease susceptibility,
      whereas Treg-cell-lineage-specific deletion of Il4 and Il13 was protective. IL-4R
      signaling impaired the capacity of Treg cells to suppress mast cell activation
      and expansion, which in turn drove Th2 cell reprogramming of Treg cells.
      Interruption of Th2 cell reprogramming of Treg cells might thus provide candidate
      therapeutic strategies in food allergy.

PMID- 25769612
TI  - CXCR3 chemokine receptor enables local CD8(+) T cell migration for the
      destruction of virus-infected cells.
AB  - CD8(+) T cells play a critical role in limiting peripheral virus replication, yet
      how they locate virus-infected cells within tissues is unknown. Here, we have
      examined the environmental signals that CD8(+) T cells use to localize and
      eliminate virus-infected skin cells. Epicutaneous vaccinia virus (VV) infection,
      mimicking human smallpox vaccination, greatly increased expression of the CXCR3
      chemokine receptor ligands CXCL9 and CXCL10 in VV-infected skin. Despite normal T
      cell numbers in the skin, Cxcr3(-/-) mice exhibited dramatically impaired CD8(+)
      T-cell-dependent virus clearance. Intravital microscopy revealed that Cxcr3(-/-)
      T cells were markedly deficient in locating, engaging, and killing virus-infected
      cells. Further, transfer of wild-type CD8(+) T cells restored viral clearance in
      Cxcr3(-/-) animals. These findings demonstrate a function for CXCR3 in enhancing
      the ability of tissue-localized CD8(+) T cells to locate virus-infected cells and
      thereby exert anti-viral effector functions.

PMID- 25769613
TI  - ICOS:ICOS-ligand interaction is required for type 2 innate lymphoid cell
      function, homeostasis, and induction of airway hyperreactivity.
AB  - Allergic asthma is caused by Th2-cell-type cytokines in response to allergen
      exposure. Type 2 innate lymphoid cells (ILC2s) are a newly identified subset of
      immune cells that, along with Th2 cells, contribute to the pathogenesis of asthma
      by producing copious amounts of IL-5 and IL-13, which cause eosinophilia and
      airway hyperreactivity (AHR), a cardinal feature of asthma. ILC2s express ICOS, a
      T cell costimulatory molecule with a currently unknown function. Here we showed
      that a lack of ICOS on murine ILC2s and blocking the ICOS:ICOS-ligand interaction
      in human ILC2s reduced AHR and lung inflammation. ILC2s expressed both ICOS and
      ICOS-ligand, and the ICOS:ICOS-ligand interaction promoted cytokine production
      and survival in ILC2s through STAT5 signaling. Thus, ICOS:ICOS-ligand signaling
      pathway is critically involved in ILC2 function and homeostasis.

PMID- 25769614
TI  - Effect of Intraoperative Dexmedetomidine on Post-Craniotomy Pain.
AB  - PURPOSE: Pain management for patients who have undergone a craniotomy remains
      challenging. This study aimed to determine whether intraoperative dexmedetomidine
      could reduce postoperative pain, analgesic consumption, and possible adverse
      events in patients after craniotomy. METHODS: Eighty patients scheduled for
      elective supratentorial craniotomy under sevoflurane-fentanyl anesthesia were
      randomly allocated into two equal groups, to receive a continuous dexmedetomidine
      infusion of 0.5 ug/kg/h or placebo, beginning after induction and continuing
      until the start of skin closure. Intravenous tramadol (0.5 mg/kg) was
      administered to achieve an 11-point verbal rating scale (a discrete 0-10 scale)
      score of 4 or less in the postanesthesia care unit and, thereafter, on the ward.
      Pain scores, tramadol consumption, sedation scores, postoperative nausea and
      vomiting (PONV) scores, and other adverse events were recorded in the first 24
      hours postoperatively. FINDINGS: Seventy-six patients were included in the
      analyses. Demographic data, surgical characteristics, and sedation levels were
      similar between the groups. Dexmedetomidine reduced pain scores (30 minutes, P =
      0.041; 2 hours, P = 0.021) and tramadol consumption (0-2 hours, P = 0.043; 0-6
      hours, P = 0.006; 0-12 hours, P = 0.023; 0-24 hours, P = 0.040) postoperatively.
      Dexmedetomidine also reduced PONV scores at 20, 60, 90, 120, and 240 minutes (P =
      0.038, 0.022, 0.018, 0.037, 0.016, respectively). The dexmedetomidine group
      exhibited fewer PONV events that required treatment (P = 0.005). IMPLICATIONS:
      Intraoperative dexmedetomidine infusion was effective for reducing pain and
      analgesic consumption after craniotomy. In addition, dexmedetomidine may help to
      reduce PONV in patients after craniotomy treated with tramadol postoperatively.
      Chinese Clinical Trial Register identifier: ChiCTR-TRC-13003598.

PMID- 25769615
TI  - Effect of age and sex on the pharmacokinetics and safety of avibactam in healthy
      volunteers.
AB  - PURPOSE: Avibactam is a novel non-beta-lactam beta-lactamase inhibitor currently
      being assessed in combination with ceftazidime, ceftaroline fosamil, and
      aztreonam. The objectives of this study were to investigate the pharmacokinetics,
      safety, and tolerability of avibactam in healthy young (aged 18-45 years) and
      elderly (aged >=65 years) volunteers of both sexes. METHODS: This was a Phase I,
      open-label study in which healthy volunteers aged >=18 years were enrolled into 4
      cohorts: young male, young female, elderly male, and elderly female (n = 8 in
      each group). Subjects were excluded if they had any condition requiring regular
      medication or any other relevant conditions. All subjects received a single dose
      of avibactam 500 mg/100 mL given intravenously over 30 minutes. Pharmacokinetic
      measurements included Cmax, Tmax, AUC0-infinity, plasma clearance, and t1/2.
      FINDINGS: Within the two age categories the mean age across male and female
      subjects was well matched. The majority of subjects in the young cohort were
      black (>=62.5%), whilst the majority of those in the elderly cohorts were white
      (>=75%). Mean avibactam plasma clearance was similar between the young male,
      young female, and elderly male cohorts (10.16, 10.34, and 9.82 L/h,
      respectively), and slightly lower in elderly women (7.98 L/h). Mean Cmax was
      similar in young male, young female, and elderly female subjects (33.8, 36.9, and
      38.4 ug/mL) but lower in elderly male subjects (26.5 ug/mL). Point estimates
      comparing the ratio of Cmax in male and female subjects over all age groups
      suggested that Cmax values were 18% lower (90% CI, 30%-5% lower) in male subjects
      compared with female subjects. Mean AUC0-infinity data were similar between the
      young male, young female, and elderly male cohorts (49.86, 49.75, and 52.40
      ug.h/mL) but higher in elderly women (66.23 ug.h/mL). Point estimates comparing
      the ratio of AUC0-infinity in elderly and young subjects across both sexes
      suggested that AUC0-infinity values were 17% higher (90% CI, 5%-31%) in elderly
      subjects compared with young subjects. The t1/2 was slightly longer for elderly
      subjects compared with younger subjects. The most common adverse event was
      administration/venipuncture site bruising (6 events); all adverse events were
      mild. IMPLICATIONS: No notable differences in pharmacokinetics were observed
      between the male and female cohorts. The generalizability of the study is limited
      due to its small sample size. However, the small differences observed between the
      young and elderly cohorts are not sufficient to warrant dosing adjustments based
      on age.

PMID- 25769616
TI  - Confirming Mycobacterium tuberculosis transmission from a cadaver to an embalmer
      using molecular epidemiology.
AB  - Genotyping results and epidemiologic investigation were used to confirm
      tuberculosis transmission from a cadaver to an embalmer. This investigation
      highlights the utility of genotyping in identifying unsuspected epidemiologic
      links and unusual transmission settings. In addition, the investigation provides
      additional evidence for the occupational risk of tuberculosis among funeral
      service workers and indicates a need for education about tuberculosis risk and
      the importance of adhering to appropriate infection control measures among
      funeral service workers. 

PMID- 25769617
TI  - Multicenter study of health care cost of patients admitted to hospital with
      Staphylococcus aureus bacteremia: Impact of length of stay and intensity of care.
AB  - BACKGROUND: Methicillin-susceptible Staphylococcus aureus (MSSA) and methicillin
      resistant S aureus bacteremia (SAB) have both been associated with high morbidity
      and mortality and heavy consumption of health care resources. We compared
      clinical and economic data for hospitalized cases of SAB in the context of a
      publicly funded health care system. METHODS: A cost analysis was undertaken on an
      adult cohort of patients from 4 hospitals with SAB diagnosed within 3 days of
      hospitalization. Primary outcome was direct cost of inpatient care per case,
      determined at discharge and itemized using a standardized methodology. RESULTS: A
      total of 435 patients were admitted with SAB; 58 had methicillin-resistant S
      aureus (MRSA). The median length of stay was similar in patients with MRSA and
      MSSA. There was no significant difference between the groups for mortality.
      Median direct medical costs of SAB were $12,078. Patients with MRSA had 1.32
      times higher direct costs than MSSA. A similar estimate was derived using a
      propensity score approach (P = .148). Human health care resources comprised >70%
      of total costs per case, whereas antibiotics comprised 1%-2%. CONCLUSION:
      Understanding the dynamics of resource consumption is critical to improving its
      efficiency and the quality of patient care. Our findings suggest that hospital
      length of stay and care intensity should be the major focus of any resource
      assessment exercise.

PMID- 25769618
TI  - A successful multifaceted strategy to improve hand hygiene compliance rates.
AB  - Health care-acquired infections are a major contributor of mortality; therefore,
      prevention of these infections is a priority. Hand hygiene compliance among
      health care workers is low. We report the process at our institution to increase
      the hand hygiene compliance rate (HHCR).We implemented interventions over 6
      months. The periods were divided into preintervention, intervention, and
      postintervention, and the monthly HHCR was calculated. The primary objective was
      to measure the HHCR after the intervention period and ensure sustainability.
      There were 25,372 observations, with 22,501 compliant events, for an overall HHCR
      of 88.7%. The HHCR improved over time (preintervention, 72.7%; invention, 79.7%;
      postintervention, 93.2%), with significance between pre-and postintervention
      periods (P < .002). The HHCR stabilized after all interventions and was sustained
      over 22 months. Our study highlights a multifaceted intervention, including
      administrative leadership, that led to an increase in the HHCR. Institutions
      should individualize their multimodal approach to include administrative
      leadership to achieve a high, sustained HHCR. 

PMID- 25769619
TI  - How I treat postpartum hemorrhage.
AB  - Worldwide, ~800 women die every day from preventable causes related to pregnancy
      or childbirth. The single most common cause is severe bleeding, which can kill a
      healthy woman within hours if care is substandard or delayed. Improved antenatal
      practices have led to the early identification of at-risk women and modern
      technology and new techniques have enabled effective management strategies so
      that now, in the western world, most of the morbidity and mortality arises from
      those cases which occur unexpectedly and could not have been predicted. Prompt
      and effective management and multidisciplinary involvement is paramount to save
      the lives of these women. We use a case report to illustrate and discuss the main
      elements of management of this condition. 

PMID- 25769620
TI  - Obinutuzumab plus fludarabine/cyclophosphamide or bendamustine in the initial
      therapy of CLL patients: the phase 1b GALTON trial.
AB  - Obinutuzumab is a type 2, glycoengineered, anti-CD20 antibody recently approved
      with chlorambucil for the initial therapy of chronic lymphocytic leukemia (CLL).
      In this nonrandomized, parallel-cohort, phase 1b, multicenter study, we explored
      the safety and preliminary efficacy of obinutuzumab-bendamustine (G-B) or
      obinutuzumab fludarabine cyclophosphamide (G-FC) for the therapy of previously
      untreated fit patients with CLL. Patients received up to 6 cycles of G-B (n = 20)
      or G-FC (n = 21). The primary end point was safety, with infusion-related
      reactions (88%, grade 3-4 20%) being the most common adverse event and grade 3-4
      neutropenia in 55% on G-B and 48% on G-FC. Mean cycles completed were 5.7 for G-B
      and 5.1 for G-FC, with 2 and 7 early discontinuations, respectively. The
      objective response rate (ORR) for G-B was 90% (18/20) with 20% complete response
      (CR) and 25% CR with incomplete marrow recovery (CRi). The ORR for G-FC was 62%
      (13/21), with 10% CR and 14% CRi, including 4 patients not evaluable. With a
      median follow-up of 23.5 months in the G-B cohort and 20.7 months in the G-FC
      cohort, no patient has relapsed or died. We conclude that obinutuzumab with
      either B or FC shows manageable toxicity and has promising activity. This study
      was registered at www.clinicaltrials.gov as #NCT01300247. 

PMID- 25769622
TI  - Gastric perforation following endoscopic removal of a Bravo pH capsule in a cat.
AB  - A 7-year-old domestic shorthair cat was evaluated for hyporexia and weight loss
      following endoscopic placement of an intragastric pH monitoring device. Physical
      examination of the cat was unremarkable, and its blood work was notable for a
      mild hypoalbuminemia. The cat's acute hyporexia and weight loss was attributed to
      discomfort associated with the intragastric pH monitoring device, as has been
      reported in humans. Endoscopic removal of the intragastric pH monitoring device
      resulted in gastric perforation. The cat underwent exploratory laparotomy for
      surgical resection and repair of the perforated area. To our knowledge, this is
      the first report of gastric perforation secondary to removal of a Bravo pH
      capsule. Caution may be advised when considering intragastric pH capsule removal
      in cats. 

PMID- 25769621
TI  - Haploidentical hematopoietic transplantation from KIR ligand-mismatched donors
      with activating KIRs reduces nonrelapse mortality.
AB  - Because activating killer cell immunoglobulinlike receptors (KIRs) are
      heterogeneously expressed in the population, we investigated the role of donor
      activating KIRs in haploidentical hematopoietic transplants for acute leukemia.
      Transplants were grouped according to presence vs absence of KIR-ligand
      mismatches in the graft-vs-host direction (ie, of donor-vs-recipient natural
      killer [NK]-cell alloreactivity). In the absence of donor-vs-recipient NK-cell
      alloreactivity, donor activating KIRs had no effects on outcomes. In the 69
      transplant pairs with donor-vs-recipient NK-cell alloreactivity, transplantation
      from donors with KIR2DS1 and/or KIR3DS1 was associated with reduced risk of
      nonrelapse mortality, largely infection related (KIR2DS1 present vs absent:
      hazard ratio [HR], 0.25; P = .01; KIR3DS1 present vs absent: HR, 0.18; P = .006),
      and better event-free survival (KIR2DS1 present vs absent: HR, 0.31; P = .011;
      KIR3DS1 present vs absent: HR, 0.30; P = .008). Transplantation from donors with
      KIR2DS1 and/or KIR3DS1 was also associated with a 50% reduction in infection rate
      (P = .003). In vitro analyses showed that KIR2DS1 binding to its HLA-C2 ligand
      upregulated inflammatory cytokine production by alloreactive NK cells in response
      to infectious challenges. Because ~40% of donors able to exert donor-vs-recipient
      NK-cell alloreactivity carry KIR2DS1 and/or KIR3DS1, searching for them may
      become a feasible, additional criterion in donor selection. 

PMID- 25769623
TI  - Effect of thyroid volume on radioiodine therapy outcome in hyperthyroid cats.
AB  - Radioiodine therapy is commonly used in hyperthyroid cats and has a high success
      rate, ranging from 85-95%. As in humans, thyroid volume has been reported to
      influence radioiodine therapy outcome in hyperthyroid cats. The purpose of this
      study was to relate total thyroid volume, calculated by a newly constructed
      formula for feline patients (0.438 * length * width2), to the outcome of
      radioiodine therapy. To search for a correlation between total thyroid volume and
      therapy outcome, 167 hyperthyroid cats were included. Patients were categorised
      according to the administered radioiodine dose and therapy outcome. Our analysis
      did not show a significant relationship between an increasing total thyroid
      volume and the odds for a final low total thyroxine concentration (TT4; P =
      0.3930) or a final hyperthyroid outcome (P = 0.0901). A significant relationship
      was found for an increase in the odds for a final low TT4 outcome with an
      increase in the number of foci detected on the pertechnetate thyroid scan (P =
      0.0238). This was not true for a final hyperthyroid outcome (P = 0.7435). The
      number of detected foci was also significantly associated with the total thyroid
      volume (P = 0.0006). Findings indicated that the presence of multiple affected
      foci influences therapy outcome towards a low TT4 outcome. Bilateral
      hyperthyroidism and its potential effect on a final low TT4 outcome should
      therefore be addressed when informing owners of the possible outcomes of
      radioiodine therapy for their cat. 

PMID- 25769624
TI  - Pedicle ties provide a rapid and safe method for feline ovariohysterectomy.
AB  - OBJECTIVES: The specific objectives of the present study were to evaluate the
      rate of hemorrhage-related complications across a large number of feline pedicle
      tie (PT) procedures, and evaluate for a difference in surgical time between
      traditional pedicle double ligation (PDL) and PT procedures. METHODS: In the
      initial phase of the study, 2136 intact female cats underwent an
      ovariohysterectomy using the PT technique. Hemorrhagic complications not detected
      intraoperatively were to be confirmed via exploratory surgery or necropsy. The
      second phase of the study recorded the duration of surgery for four groups:
      kittens undergoing PTs (n = 50), kittens undergoing PDL (n = 49), adult cats
      undergoing PTs (n = 50) and adult cats undergoing PDL (n = 54). Kittens were
      defined as a cat 4 months old or younger. Statistical comparisons of age, body
      weight and surgical times between the PT and PDL groups were performed within,
      but not between, kitten and adult cat categories. RESULTS: Six of 2136 (0.281%)
      cats experienced a hemorrhage-related complication associated with the ovarian
      pedicle. Five of the six ovarian pedicle hemorrhage-related complications were
      recognized and corrected intraoperatively, with the remaining hemorrhagic event
      being detected postoperatively. Surgical times were significantly shorter in PT
      kittens compared with PDL kittens (4.7 +/- 0.1 mins vs 6.7 +/- 0.1 mins) and PT
      adult cats compared with PDL adult cats (5.0 +/- 0.2 mins vs 7.0 +/- 0.2 mins).
      CONCLUSIONS AND RELEVANCE: This study demonstrates that the PT technique is
      associated with a very low risk of hemorrhage-related complications and is
      significantly faster than double ligating the ovarian pedicle in kittens and
      adult cats. Use of the PT technique has the potential to be of significant
      economic benefit in institutions performing large numbers of feline
      ovariohysterectomies.

PMID- 25769625
TI  - The role of biomarkers and MEG-based imaging markers in the diagnosis of post
      traumatic stress disorder and blast-induced mild traumatic brain injury.
AB  - BACKGROUND: Pervasive use of improvised explosive devices (IEDs), rocket
      propelled grenades, and land mines in the recent conflicts in Iraq and
      Afghanistan has brought traumatic brain injury (TBI) and its impact on health
      outcomes into public awareness. Blast injuries have been deemed signature wounds
      of these wars. War-related TBI is not new, having become prevalent during WWI and
      remaining medically relevant in WWII and beyond. Medicine's past attempts to
      accurately diagnose and disentangle the pathophysiology of war-related TBI
      parallels current lines of inquiry and highlights limitations in methodology and
      attribution of symptom etiology, be it organic, psychological, or behavioral. New
      approaches and biomarkers are needed. PRECLINICAL: Serological biomarkers and
      biomarkers of injury obtained with imaging techniques represent cornerstones in
      the translation between experimental data and clinical observations. Experimental
      models for blast related TBI and PTSD can generate critical data on injury
      threshold, for example for white matter injury from acceleration. Carefully
      verified and validated models can be evaluated with gene expression arrays and
      proteomics to identify new candidates for serological biomarkers. Such models can
      also be analyzed with diffusion MRI and microscopy in order to identify criteria
      for detection of diffuse white matter injuries, such as DAI (diffuse axonal
      injury). The experimental models can also be analyzed with focus on injury
      outcome in brain stem regions, such as locus coeruleus or nucleus raphe magnus
      that can be involved in response to anxiety changes. CLINICAL: Mild (and some
      moderate) TBI can be difficult to diagnose because the injuries are often not
      detectable on conventional MRI or CT. There is accumulating evidence that injured
      brain tissues in TBI patients generate abnormal low-frequency magnetic activity
      (ALFMA, peaked at 1-4Hz) that can be measured and localized by
      magnetoencephalography (MEG). MEG imaging detects TBI abnormalities at the rates
      of 87% for the mild TBI, group (blast-induced plus non-blast causes) and 100% for
      the moderate group. Among the mild TBI patients, the rates of abnormalities are
      96% and 77% for the blast and non-blast TBI groups, respectively. There is
      emerging evidence based on fMRI and MEG studies showing hyper-activity in the
      amygdala and hypo-activity in pre-frontal cortex in individuals with PTSD. MEG
      signal may serve as a sensitive imaging marker for mTBI, distinguishable from
      abnormalities generated in association with PTSD. More work is needed to fully
      describe physiological mechanisms of post-concussive symptoms.

PMID- 25769627
TI  - Responses to the editor RE: McCullough PA, Roberts WC. Peter Andrew McCullough,
      MD, MPH: An interview with the editor. Am J Cardiol 2014;114:1772-1785.

PMID- 25769626
TI  - Effect of dietary sodium and potassium intake on left ventricular diastolic
      function and mass in adults<=40 years (from the Strong Heart Study).
AB  - The aim of this study was to investigate whether intake of dietary sodium or
      potassium is related to changes in left ventricular (LV) diastolic functioning
      and LV mass index in young subjects with normal or elevated blood pressure. We
      prospectively analyzed echocardiographic data in 1,065 young adults (18 to 39
      years) enrolled in the Strong Heart Family Study who were free from
      cardiovascular disease at baseline: 501 (47%) participants were normotensive and
      564 (53%) were prehypertensive or hypertensive. Dietary sodium and potassium
      intakes were ascertained using a block food frequency questionnaire at baseline.
      Cardiac geometry and functioning were assessed at baseline and 4 years later.
      Marginal models were used to assess the associations of average intakes of sodium
      and potassium with echocardiographic measures. Participants with prehypertension
      or hypertension were older, had higher body mass index, and reported higher
      intakes of sodium than normotensive subjects at baseline. In prospective
      analyses, potassium intake was found to be negatively related to mitral E
      velocity (p=0.029) in normotensive subjects, whereas sodium/potassium ratio was
      positively associated with atrial filling fraction (p=0.017). In prehypertensive
      or hypertensive participants, sodium consumption was positively associated with
      atrial filling fraction (p=0.034) and an increase in sodium/potassium ratio was
      related to higher LV mass index (p=0.046). In conclusion, an increase in dietary
      sodium/potassium ratio was related to an accentuation of atrial phase LV
      diastolic filling in normotensive young subjects, whereas in prehypertensive or
      hypertensive subjects it was associated with higher LV mass index.

PMID- 25769628
TI  - Diffuse interstitial fibrosis and myocardial dysfunction in early chronic kidney
      disease.
AB  - Early-stage chronic kidney disease (CKD) is an under-recognized highly prevalent
      cardiovascular (CV) risk factor. Despite a clustering of conventional
      atherosclerotic risk factors, it is hypothesized that nonatherosclerotic
      processes, including left ventricular (LV) hypertrophy and fibrosis, account for
      a significant excess of CV risk. This cross-sectional observational study of 129
      age- (mean age 57+/-10 years) and gender-matched subjects examined: nondiabetic
      CKD stages 2 to 4 (mean glomerular filtration rate 50+/-22 ml/min/1.73 m2) with
      no history of CV disease, subjects who are hypertensive with normal renal
      function, and healthy controls. Cardiac magnetic resonance imaging was performed
      for assessment of LV volumes and systolic function (myocardial deformation).
      Diffuse myocardial fibrosis was assessed using T1 mapping for native myocardial
      T1 times before contrast and myocardial extracellular volume (ECV) after
      gadolinium administration in combination with standard late gadolinium
      enhancement techniques for detection of coarse fibrosis. Patients with CKD had
      increased native T1 times (986+/-37 ms) and ECV (0.28+/-0.04) compared with
      controls (955+/-30 ms, 0.25+/-0.03) and subjects who are hypertensive (956+/-31
      ms, 0.25+/-0.02, p<0.05). Both T1 times and ECV were correlated with impaired
      systolic function as assessed by global longitudinal systolic strain (r=-0.22,
      p<0.05, and r=-0.43, p<0.01, respectively). There were no differences in LV
      volumes, ejection fraction, or LV mass. T1 times and ECV did not correlate with
      conventional CV risk factors. In conclusion, diffuse myocardial fibrosis is
      increased in early CKD and is associated with abnormal global longitudinal
      strain, an early feature of uremic cardiomyopathy and a key indicator of adverse
      CV prognosis.

PMID- 25769629
TI  - [New insights in the antiphospholipid syndrome associated vasculitis: the role of
      the AKT/mTORC pathway].

PMID- 25769630
TI  - Task Force 8: Pediatric Cardiology Fellowship Training in Research and Scholarly
      Activity. SPCTPD/ACC/AAP/AHA.

PMID- 25769631
TI  - Task Force 7: Pediatric Cardiology Fellowship Training in Pulmonary Hypertension,
      Advanced Heart Failure, and Transplantation. SPCTPD/ACC/AAP/AHA.

PMID- 25769632
TI  - Task Force 1: Pediatric Cardiology Fellowship Training in General Cardiology.
      SPCTPD/ACC/AAP/AHA.

PMID- 25769633
TI  - Task Force 2: Pediatric Cardiology Fellowship Training in Noninvasive Cardiac
      Imaging. SPCTPD/ACC/AAP/AHA.

PMID- 25769634
TI  - Task Force 5: Pediatric Cardiology Fellowship Training in Critical Care
      Cardiology. SPCTPD/ACC/AAP/AHA.

PMID- 25769635
TI  - Task Force 3: Pediatric Cardiology Fellowship Training in Cardiac
      Catheterization. SPCTPD/ACC/AAP/AHA.

PMID- 25769637
TI  - Task Force 4: Pediatric Cardiology Fellowship Training in Electrophysiology.
      SPCTPD/ACC/AAP/AHA.

PMID- 25769638
TI  - Task Force 6: Pediatric Cardiology Fellowship Training in Adult Congenital Heart
      Disease. SPCTPD/ACC/AAP/AHA.

PMID- 25769639
TI  - 2015 SPCTPD/ACC/AAP/AHA Training Guidelines for Pediatric Cardiology Fellowship
      Programs (Revision of the 2005 Training Guidelines for Pediatric Cardiology
      Fellowship Programs): Introduction.

PMID- 25769641
TI  - Editorial: Gene therapy for gastrointestinal and liver cancers: past experience,
      current status and future perspectives.

PMID- 25769642
TI  - Letter regarding "interference of doxycycline pretreatment in a model of
      abdominal aortic aneurysms".

PMID- 25769640
TI  - Long-term outcomes of secondary atrial fibrillation in the community: the
      Framingham Heart Study.
AB  - BACKGROUND: Guidelines have proposed that atrial fibrillation (AF) can occur as
      an isolated event, particularly when precipitated by a secondary, or reversible,
      condition. However, knowledge of long-term AF outcomes after diagnosis during a
      secondary precipitant is limited. METHODS AND RESULTS: In 1409 Framingham Heart
      Study participants with new-onset AF, we examined associations between first
      detected AF episodes occurring with and without a secondary precipitant and both
      long-term AF recurrence and morbidity. We selected secondary precipitants based
      on guidelines (surgery, infection, acute myocardial infarction, thyrotoxicosis,
      acute alcohol consumption, acute pericardial disease, pulmonary embolism, or
      other acute pulmonary disease). Among 439 patients (31%) with AF diagnosed during
      a secondary precipitant, cardiothoracic surgery (n=131 [30%]), infection (n=102
      [23%]), noncardiothoracic surgery (n=87 [20%]), and acute myocardial infarction
      (n=78 [18%]) were most common. AF recurred in 544 of 846 eligible individuals
      without permanent AF (5-, 10-, and 15-year recurrences of 42%, 56%, and 62% with
      versus 59%, 69%, and 71% without secondary precipitants; multivariable-adjusted
      hazard ratio, 0.65 [95% confidence interval, 0.54-0.78]). Stroke risk (n=209/1262
      at risk; hazard ratio, 1.13 [95% confidence interval, 0.82-1.57]) and mortality
      (n=1098/1409 at risk; hazard ratio, 1.00 [95% confidence interval, 0.87-1.15])
      were similar between those with and without secondary precipitants, although
      heart failure risk was reduced (n=294/1107 at risk; hazard ratio, 0.74 [95%
      confidence interval, 0.56-0.97]). CONCLUSIONS: AF recurs in most individuals,
      including those diagnosed with secondary precipitants. Long-term AF-related
      stroke and mortality risks were similar between individuals with and without
      secondary AF precipitants. Future studies may determine whether increased
      arrhythmia surveillance or adherence to general AF management principles in
      patients with reversible AF precipitants will reduce morbidity.

PMID- 25769643
TI  - IL28B rs12980275 variant as a predictor of sustained virologic response to
      pegylated-interferon and ribavirin in chronic hepatitis C patients: A systematic
      review and meta-analysis.
AB  - BACKGROUND AND OBJECTIVE: The IL-28B rs12979860 CC and rs8099917 TT genotypes
      were proved to be predictor for pegylated-interferon (PEG-IFN)/ribavirin (RBV)
      treated hepatitis C virus (HCV) patients. However, there were no identical
      conclusions on rs12980275 polymorphism. Our aim is to perform a meta-analysis in
      order to determine the association between rs12980275 polymorphism of IL28B and
      the sustain viral response (SVR) of HCV patients with PEG-IFN/RBV therapy.
      METHODS: Studies were retrieved from PubMed and Chinese China National Knowledge
      Infrastructure (CNKI). Data were extracted by two investigators and analyzed
      using Stata 11.0 software. RESULTS: Sixteen articles, containing 19 independent
      studies were included in the analysis. The results showed that patients with AA
      genotype of rs12980275 achieved higher SVR than patients with AG/GG genotypes.
      The overall OR (95% CI) was 3.118 (2.146, 4.529). In subgroup analysis by
      ethnicity, the ORs (95% CIs) were 3.084 (1.454, 6.542) and 2.736 (1.863, 4.018)
      in Asian and Caucasian population, respectively. Another subgroup analysis by HCV
      genotype, the ORs (95% CIs) were 3.976 (2.568, 6.158), 1.462 (0.504, 4.240) and
      1.489 (0.916, 2.421) in patients with HCV genotype 1/4, mix genotype, and HCV
      genotype 2/3, respectively. CONCLUSION: AA genotype of rs12980275 was a
      predictive factor for SVR in HCV patients with PEG-IFN/RBV treatment, especially
      in HCV genotype 1/4.

PMID- 25769644
TI  - IFAT and ELISA phase I/phase II as tools for the identification of Q fever
      chronic milk shedders in cattle.
AB  - Q fever is a widespread zoonotic disease caused by Coxiella burnetii. In cattle
      the bacterial shedding can persist without symptoms for several months and the
      shedders identification is a critical issue in the control of the infection at
      herd level. Following the example of the human protocols for the assessment of Q
      fever infection status, the aim of this study was the evaluation of the antibody
      response dynamics to phase I and phase II antigens in C. burnetii shedder dairy
      cows by means of a phase-specific serology, to verify the suitability of the
      investigated tools in recognising milk shedders. A total of 99 cows were
      monitored during time and classified on the basis of serological and PCR results
      in five groups identifying different shedding patterns. The 297 sera collected in
      three sampling times were tested by means of ELISA IgG for differential phase I
      and phase II antibodies detection, while a selection of 107 sera were tested by
      means of phase specific IgM and IgG IFAT. Both ELISA IgG and IFAT IgG highlighted
      a low reactivity in non-shedder seropositive animals compared to chronic milk
      shedder animals. ELISA IgG seemed to perform better than IFAT IgG-IgM, showing
      significant serological differences among groups that allowed recognising
      specific serological group patterns, in particular for chronic and occasional
      milk shedders. These results supported the hypothesis that an animal
      classification based on phase patterns is reasonable, although it needs to be
      further investigated. 

PMID- 25769645
TI  - Adaptive amino acid substitutions enhance the virulence of an H7N7 avian
      influenza virus isolated from wild waterfowl in mice.
AB  - Although H7N7 AIVs primarily circulate in wild waterfowl, documented cases of
      human infection with H7N7 viruses suggest they may pose a pandemic threat. Here,
      we generated mouse-adapted variants of a wild waterfowl-origin H7N7 virus to
      identify adaptive changes that confer enhanced virulence in mammals. The mouse
      lethal doses (MLD50) of the adapted variants were reduced >5000-fold compared to
      the parental virus. Mouse-adapted variants viruses displayed enhanced replication
      in vitro and in vivo, and acquired the ability to replicate in extrapulmonary
      tissues. These observations suggest that enhanced growth characteristics and
      modified cell tropism may increase the virulence of H7N7 AIVs in mice. Genomic
      analysis of the adapted variant viruses revealed amino acid changes in the PB2
      (E627K), PB1 (R118I), PA (L550M), HA (G214R), and NA (S372N) proteins. Our
      results suggest that these amino acid substitutions collaboratively enhance the
      ability of H7N7 virus to replicate and cause severe disease in mammals. 

PMID- 25769646
TI  - Cross-protection of a new type 2 porcine reproductive and respiratory syndrome
      virus (PRRSV) modified live vaccine (Fostera PRRS) against heterologous type 1
      PRRSV challenge in growing pigs.
AB  - The objective of the present study was to determine the cross-protection of a new
      type 2 porcine reproductive and respiratory syndrome virus (PRRSV) modified live
      vaccine against heterologous type 1 PRRSV challenge in growing pigs. The mean
      rectal temperature and respiratory score was significantly (P<0.05) lower in
      vaccinated challenged pigs than in unvaccinated challenged pigs. Vaccination of
      pigs with type 2 PRRSV reduced the levels of type 1 PRRSV viremia after challenge
      with type 1 PRRSV. Vaccinated challenged pigs had significantly (P<0.05) higher
      frequency of interferon-gamma secreting cells and lower levels of interleukin-10
      compared to unvaccinated challenged pigs. Vaccination of pigs with the type 2
      PRRSV effectively reduced the macroscopic and microscopic lung lesion and the
      type 1 PRRSV antigens within lung lesions in vaccinated challenged pigs. This
      study demonstrates partial cross-protection of a new type 2 PRRSV modified live
      vaccine against heterologous type 1 PRRSV challenge in growing pigs. 

PMID- 25769648
TI  - [Is paraoxonase 1 a marker of cardiovascular risk in youth with type 1 diabetes?
      (Study about 109 cases)].
AB  - OBJECTIVES: We purpose to verify if paraoxonase 1 (PON1) activity may be a marker
      of cardiovascular risk in a young Tunisian population with type 1 diabetes (T1D).
      METHODS: PON1 activity was measured by a kinetic method using paraoxon as
      substrate. The other parameters were determined by automated methods. RESULTS:
      One hundred and nine children and adolescents with T1D and 97 healthy subjects
      were involved in this study. PON1 activity and PON1/HDL-cholesterol ratio were
      significantly decreased in diabetics (303 +/- 174 vs. 372 +/- 180 U/L and 221 +/-
      139 vs. 298 +/- 20 1U/mmol, P=0.006, P=0.002, respectively) compared to controls.
      A significant increase in total cholesterol, LDL-c and microalbuminuria was
      observed in diabetics compared to controls. PON1 activity was decreased by 9.5%
      in patients with diabetes duration >= 6 years, by 28.4% for those with fasting
      glycemia >= 7 mmol/L (P<0.001), by 14% in those with HbA1c >= 8% and by 12.3% for
      diabetics with dyslipidemia. PON1 activity is reduced when the number of
      cardiovascular risk factors increases (P<0.001). CONCLUSION: PON1 seems to be
      associated to cardiovascular risk markers in T1D. This result remains to be seen.
      Nevertheless, improving PON1 activity could be a significant target for reducing
      cardiovascular risk.

PMID- 25769647
TI  - Comparative analysis of cellular immune responses and cytokine levels in sheep
      experimentally infected with bluetongue virus serotype 1 and 8.
AB  - Protective immunity in sheep with bluetongue virus (BTV) infection as well as the
      role of BTV-induced cytokines during immune response remains unclear.
      Understanding the basis immunological mechanisms in sheep experimentally infected
      with serotypes 1 and 8 (BTV-1 and -8) was the aim of this study. A time-course
      study was carried out in order to evaluate cell-mediated immune response and
      serum concentrations of cytokines (IL-1beta, TNFalpha, IL-12, IFNgamma, IL-4 and
      IL-10) with inflammatory and immunological functions. Depletion of T cell subsets
      (mainly CD4(+), gammadelta and CD25(+)) together with the absence of cytokines
      (IFNgamma and IL-12) involved in the regulation of cell-mediated antiviral
      immunity at the first stage of the disease suggested that both BTV-1 and BTV-8
      might impair host's capability against primary infections which would favor viral
      replication and spreading. However, cellular immune response and cytokines
      elicited an immune response in sheep that efficiently reduced viremia in the
      final stage of the experiment. Recovery of T cell subsets (CD4(+) and CD25(+))
      together with a significant increase of CD8(+) T lymphocytes in both infected
      groups were observed in parallel with the decrease of viremia. Additionally, the
      recovery of CD4(+) T lymphocytes together with the significant increase of IL-4
      serum levels at the final stage of the experiment might contribute to humoral
      immune response activation and neutralizing antibodies production against BTV
      previously described in the course of this experiment. These results suggested
      that both cellular and humoral immune response may contribute to protective
      immunity against BTV-1 and BTV-8 in sheep. The possible role played by IL-10 and
      CD25(+) cells in controlling inflammatory and immune response in the final stage
      of the experiment has also been suggested. 

PMID- 25769649
TI  - Osteoblast function and bone histomorphometry in a murine model of Rett syndrome.
AB  - Rett syndrome (RTT) is an X-linked neurodevelopmental disorder due to mutations
      affecting the neural transcription factor MeCP2. Approximately 50% of affected
      females have decreased bone mass. We studied osteoblast function using a murine
      model of RTT. Female heterozygote (HET) and male Mecp2-null mice were compared to
      wild type (WT) mice. Micro-CT of tibia from 5 week-old Mecp2-null mice showed
      significant alterations in trabecular bone including reductions in bone volume
      fraction (-29%), number (-19%), thickness (-9%) and connectivity density (-32%),
      and increases in trabecular separation (+28%) compared to WT. We also found
      significant reductions in cortical bone thickness (-18%) and in polar moment of
      inertia (-45%). In contrast, cortical and trabecular bone from 8 week-old WT and
      HET female mice were not significantly different. However, mineral apposition
      rate, mineralizing surface and bone formation rate/bone surface were each
      decreased in HET and Mecp2-null mice compared to WT mice. Histomorphometric
      analysis of femurs showed decreased numbers of osteoblasts but similar numbers of
      osteoclasts compared to WT, altered osteoblast morphology and decreased tissue
      synthesis of alkaline phosphatase in Mecp2-null and HET mice. Osteoblasts
      cultured from Mecp2-null mice, which unlike WT osteoblasts did not express MeCP2,
      had increased growth rates, but reductions in mRNA expression of type I collagen,
      Runx2 and Osterix compared to WT osteoblasts. These results indicate that MeCP2
      deficiency leads to altered bone growth. Osteoblast dysfunction was more marked
      in Mecp2-null male than in HET female mice, suggesting that expression of MeCP2
      plays a critical role in bone development.

PMID- 25769650
TI  - [Preoperative chemoradiotherapy for rectal cancer: experience from one centre].
AB  - PURPOSE: In recent decades, the management of rectal cancer has been
      significantly improved by optimizing the surgical treatment with the total
      mesorectal excision and the development of neoadjuvant radiotherapy with or
      without chemotherapy. In this study, we investigated the impact of changes in
      practice over a period of 15 years in an expert centre. PATIENTS AND METHODS: A
      monocentric study was conducted retrospectively on cT3-resectable T4 patients who
      received chemoradiotherapy for a locally advanced rectal adenocarcinoma between
      1993 and 2008. We studied sphincter preservation, pathological complete response
      (ypT0), survival, and toxicities by different concomitant chemotherapy and
      treatment period. RESULTS: Among the 179 patients who had a chemoradiotherapy,
      56.4% were received concomitant 5-fluoro-uracil-leucovorin, 28.5% with
      concomitant capecitabine, and 15.1% with concomitant oxaliplatin and
      capecitabine. The average dose of radiotherapy was 45 Gy (25*1.8 Gy). Five-year
      disease-free survival was 74.3% and overall survival 68.8%. The rate of local
      recurrence and distant metastases were 6.1 and 23.6%. In multivariate analysis,
      concomitant chemotherapy oxaliplatin and capecitabine improved the pathological
      complete response rate (ypT0; capecitabine: 6%, 5-fluoro-uracil-leucovorin:
      10.3%, capecitabine-oxaliplatin: 22.2%), but not significantly (P=0.12) and with
      more toxicities, and treatment interruptions. Sphincter preservation rate was not
      improved significantly during the study period (1993-2004 vs. 2005-2008), but
      disease-free survival improved from 72.2% up to 87.5% (P=0.03). CONCLUSION: Our
      results are consistent with those published in the literature. Concomitant
      chemotherapy with 5-fluoro-uracil or capecitabine remains the standard scheme.
      Upfront chemotherapy, before chemoradiotherapy, should be investigated with
      regard to the predominance of metastasis.

PMID- 25769651
TI  - Dual optical recordings for action potentials and calcium handling in induced
      pluripotent stem cell models of cardiac arrhythmias using genetically encoded
      fluorescent indicators.
AB  - Reprogramming of human somatic cells to pluripotency has been used to investigate
      disease mechanisms and to identify potential therapeutics. However, the methods
      used for reprogramming, in vitro differentiation, and phenotyping are still
      complicated, expensive, and time-consuming. To address the limitations, we first
      optimized a protocol for reprogramming of human fibroblasts and keratinocytes
      into pluripotency using single lipofection and the episomal vectors in a 24-well
      plate format. This method allowed us to generate multiple lines of integration
      free and feeder-free induced pluripotent stem cells (iPSCs) from seven patients
      with cardiac diseases and three controls. Second, we differentiated human iPSCs
      derived from patients with Timothy syndrome into cardiomyocytes using a monolayer
      differentiation method. We found that Timothy syndrome cardiomyocytes showed
      slower, irregular contractions and abnormal calcium handling compared with the
      controls. The results are consistent with previous reports using a retroviral
      method for reprogramming and an embryoid body-based method for cardiac
      differentiation. Third, we developed an efficient approach for recording the
      action potentials and calcium transients simultaneously in control and patient
      cardiomyocytes using genetically encoded fluorescent indicators, ArcLight and R
      GECO1. The dual optical recordings enabled us to observe prolonged action
      potentials and abnormal calcium handling in Timothy syndrome cardiomyocytes. We
      confirmed that roscovitine rescued the phenotypes in Timothy syndrome
      cardiomyocytes and that these findings were consistent with previous studies
      using conventional electrophysiological recordings and calcium imaging with dyes.
      The approaches using our optimized methods and dual optical recordings will
      improve iPSC applicability for disease modeling to investigate mechanisms
      underlying cardiac arrhythmias and to test potential therapeutics. 

PMID- 25769652
TI  - Fetal endothelial and mesenchymal progenitors from the human term placenta:
      potency and clinical potential.
AB  - Since the isolation of fetal stem cell populations from perinatal tissues, such
      as umbilical cord blood and placenta, interest has been growing in understanding
      their greater plasticity compared with adult stem cells and exploring their
      potential in regenerative medicine. The phenomenon of fetal microchimerism (FMC)
      naturally occurring during pregnancy through the transfer of fetal
      stem/progenitor cells to maternal blood and tissues has been integral in
      developing this dogma. Specifically, microchimeric mesenchymal stem cells and
      endothelial progenitors of fetal origin have now demonstrated a capacity for
      tissue repair in the maternal host. However, the use of similar fetal stem cells
      in therapy has been significantly hampered by the availability of clinically
      relevant cell numbers and/or contamination with cells of maternal origin,
      particularly when using the chorionic and decidual placenta. In the present
      prospective review, we highlight the importance of FMC to the field of fetal stem
      cell biology and issues of maternal contamination from perinatal tissues and
      discuss specific isolation strategies to overcome these translational obstacles.

PMID- 25769653
TI  - Development of a universal RNA beacon for exogenous gene detection.
AB  - Stem cell therapy requires a nontoxic and high-throughput method to achieve a
      pure cell population to prevent teratomas that can occur if even one cell in the
      implant has not been transformed. A promising method to detect and separate cells
      expressing a particular gene is RNA beacon technology. However, developing a
      successful, specific beacon to a particular transfected gene can take months to
      develop and in some cases is impossible. Here, we report on an off-the-shelf
      universal beacon that decreases the time and cost of applying beacon technology
      to select any living cell population transfected with an exogenous gene. 

PMID- 25769655
TI  - Hepatitis-E virus associated neuralgic amyotrophy with sustained plexus
      brachialis swelling visualized by high-resolution ultrasound.

PMID- 25769654
TI  - Adipose-derived stem cells from diabetic mice show impaired vascular
      stabilization in a murine model of diabetic retinopathy.
AB  - Diabetic retinopathy is characterized by progressive vascular dropout with
      subsequent vision loss. We have recently shown that an intravitreal injection of
      adipose-derived stem cells (ASCs) can stabilize the retinal microvasculature,
      enabling repair and regeneration of damaged capillary beds in vivo. Because an
      understanding of ASC status from healthy versus diseased donors will be important
      as autologous cellular therapies are developed for unmet clinical needs, we took
      advantage of the hyperglycemic Akimba mouse as a preclinical in vivo model of
      diabetic retinopathy in an effort aimed at evaluating therapeutic efficacy of
      adipose-derived stem cells (mASCs) derived either from healthy, nondiabetic or
      from diabetic mice. To these ends, Akimba mice received intravitreal injections
      of media conditioned by mASCs or mASCs themselves, subsequent to development of
      substantial retinal capillary dropout. mASCs from healthy mice were more
      effective than diabetic mASCs in protecting the diabetic retina from further
      vascular dropout. Engrafted ASCs were found to preferentially associate with the
      retinal vasculature. Conditioned medium was unable to recapitulate the
      vasoprotection seen with injected ASCs. In vitro diabetic ASCs showed decreased
      proliferation and increased apoptosis compared with healthy mASCs. Diabetic ASCs
      also secreted less vasoprotective factors than healthy mASCs, as determined by
      high-throughput enzyme-linked immunosorbent assay. Our findings suggest that
      diabetic ASCs are functionally impaired compared with healthy ASCs and support
      the utility of an allogeneic injection of ASCs versus autologous or conditioned
      media approaches in the treatment of diabetic retinopathy. 

PMID- 25769656
TI  - Differential expression of vascular endothelial growth factor in human fetal
      skeletal site-specific tissues: Mandible versus femur.
AB  - Vascular endothelial growth factor (VEGF) is a well-known mediator that signals
      through pathways in angiogenesis and osteogenesis. Angiogenesis and bone
      formation are coupled during either skeletal development or bone remodeling and
      repair occurring in postnatal life. In this study, we examined for the first time
      the expression of VEGF in human fetal mandibular and femoral bone in comparison
      with the respective adult tissues. Similarly to other craniofacial bones, but at
      variance with the axial and appendicular skeleton, during development mandible
      does not arise from mesoderm but neural crest cells of the neuroectoderm germ
      layer, and undergoes intramembranous instead of endochondral ossification. By
      quantitative real-time PCR technique, we could show that VEGF gene expression
      levels were significantly higher in fetal than in adult samples, especially in
      femoral tissue. Western blotting analysis confirmed higher protein expression of
      VEGF in the fetal femur respect to the mandible. Moreover, immunohistochemistry
      revealed that in both fetal tissues VEGF expression was mainly localized in pre-
      and osteoblasts. Differential expression of VEGF in femoral and mandibular bone
      tissues could be related to their different structure, function and development
      during organogenesis. 

PMID- 25769659
TI  - Comparison of cold knife cone biopsy and loop electrosurgical excision procedure
      in the management of cervical adenocarcinoma in situ: What is the gold standard?
AB  - OBJECTIVE: To compare the outcomes of patients with cervical adenocarcinoma in
      situ (ACIS) treated with cold knife cone (CKC) biopsy or loop electrosurgical
      excision procedure (LEEP) for the treatment of cervical adenocarcinoma in situ
      (ACIS). STUDY DESIGN: This is a retrospective, population-based cohort study of
      Western Australian patients with ACIS diagnosed between 2001 and 2012. Outcomes
      included pathological margin status and the incidence of persistent or recurrent
      endocervical neoplasia (ACIS and adenocarcinoma) during follow-up (<12 months)
      and surveillance (>=12 months) periods. RESULTS: The study group comprised 338
      patients including 107 (32%) treated initially by LEEP and 231 (68%) treated by
      CKC biopsy. The mean age was 33.2 years (range 18 to 76 years) and median follow
      up interval was 3.6 years (range <1 year to 11.8 years). Overall, 27 (8.0%)
      patients had ACIS persistence/recurrence while 9 (2.7%) were diagnosed with
      adenocarcinoma during the follow-up and surveillance periods. No patient died of
      cervical cancer within the study period. There were no significant differences in
      the incidence of persistent and/or recurrent endocervical neoplasia according to
      the type of excisional procedure. Patients with positive biopsy margins were 3.4
      times more likely to have disease persistence or recurrence. CONCLUSION(S): LEEP
      and CKC biopsy appear equally effective in the treatment of ACIS for women
      wishing to preserve fertility. Patients undergoing conservative management for
      ACIS should be closely monitored, particularly if biopsy margins are positive in
      initial excision specimens. Patients and their clinicians should be aware of the
      potential risks of residual and recurrent disease.

PMID- 25769660
TI  - Recurrent urinary tract infections in acute psychosis.

PMID- 25769657
TI  - Treatment monitoring of patients with epithelial ovarian cancer using invasive
      circulating tumor cells (iCTCs).
AB  - GOALS: Contemporary management of epithelial ovarian cancer (EOC) uses biomarkers
      to monitor response to therapy. This study evaluates the role of invasive
      circulating tumor cells (iCTCs) in monitoring EOC treatment in comparison with
      serum cancer antigen 125 (CA125). METHODS: Molecular and microscopic analyses
      were used to identify seprase and CD44 as tumor progenitor (TP) markers. The iCTC
      flow cytometry assay was optimized using blood donated by 64 healthy donors, 49
      patients with benign abdominal diseases and 123 EOC patients. Serial changes in
      iCTCs and CA125 were measured in 129 blood and 169 serum samples, respectively,
      from 31 EOC patients to assess their concordance during therapy and their
      relationship with risk of progressive disease (PD). RESULTS: The assay had 97%
      specificity and 83% sensitivity for detecting iCTCs in blood of EOC patients.
      iCTCs were detected in each monitoring patient (31/31, 100%) and in 110 of the
      129 blood samples (85.3%). The concordance between changes in iCTCs/CA125 levels
      and changes in the intervals associated with no evidence of disease (NED) were
      markedly stronger (specificity: CA125 93.8%; iCTCs 90.6%), whereas increases in
      iCTCs (79.5%) were more sensitive than increases in CA125 (67.6%) to predict PD
      or relapse. Among the six patients who had greater than 6 measurements, iCTCs but
      not CA125 antedated changes in clinical status from PD to NED during and after
      chemotherapy and predated relapse. CONCLUSION: Serial measurements of iCTCs could
      predict therapeutic responsiveness in 31 EOC patients who underwent standard
      taxol/carboplatin therapy.

PMID- 25769658
TI  - A phase II study of single-agent RO4929097, a gamma-secretase inhibitor of Notch
      signaling, in patients with recurrent platinum-resistant epithelial ovarian
      cancer: A study of the Princess Margaret, Chicago and California phase II
      consortia.
AB  - PURPOSE: A phase II study was performed to evaluate the efficacy and safety of
      single-agent RO4929097 (a gamma-secretase inhibitor) in patients with recurrent
      platinum-resistant ovarian cancer. EXPERIMENTAL DESIGN: Women with progressive
      platinum-resistant ovarian cancer treated with <=2 chemotherapy regimens for
      recurrent disease were enrolled in this trial. Patients received oral RO4929097
      at 20 mg once daily, 3 days on/4 days off each week in a three week cycle. The
      primary endpoint was progression-free survival (PFS) rate at the end of 4 cycles.
      Secondary objectives included assessment of the safety of RO4929097 and
      exploration of molecular correlates of outcome in archival tumor tissue and
      serum. RESULTS: Of 45 patients enrolled, 40 were evaluable for response. Thirty
      seven (82%) patients had high-grade ovarian cancer. No objective responses were
      observed. Fifteen patients (33%) had stable disease as their best response, with
      a median duration of 3.1 months. The median PFS for the whole group was 1.3
      months (1.2-2.5). Treatment was generally well tolerated with 10% of patients
      discontinuing treatment due to an adverse event. In high grade serous ovarian
      cancer patients, the median PFS trended higher when the expression of
      intracellular Notch (NICD) protein by immunohistochemistry was high versus low
      (3.3 versus 1.3 months, p=0.09). No clear relationship between circulating
      angiogenic factors and PFS was found despite a suggestion of an improved outcome
      with higher baseline VEGFA levels. CONCLUSIONS: RO4929097 has insufficient
      activity as a single-agent in platinum-resistant ovarian cancer to warrant
      further study as monotherapy. Future studies are needed to explore the potential
      for cohort enrichment using NICD expression.

PMID- 25769661
TI  - Ocular surface involvements in ectrodactyly-ectodermal dysplasia-cleft syndrome.
AB  - PURPOSE: To present the ocular manifestation of 2 cases of ectrodactyly
      ectodermal dysplasia-cleft syndrome, a multiple congenital anomaly syndrome
      caused by a single point mutation of the p63 gene that controls epidermal
      development and homeostasis and to present treatment options. CASE REPORTS AND
      DISCUSSION: Patient 1 presented with mild signs and symptoms of dry eye and
      limbal stem cell deficiency with retention of 20/30 vision. Patient 2 presented
      with severe signs and symptoms of limbal stem cell deficiency with diffuse
      corneal scarring and counting fingers vision. This second patient's course was
      complicated by allergic conjunctivitis and advanced steroid-induced glaucoma. The
      cause of visual loss in ectrodactyly-ectodermal dysplasia-cleft syndrome appears
      to be multifactorial and likely includes inflammation of the ocular surface, tear
      film abnormalities, eyelid abnormalities, and limbal stem cell deficiency.
      Treatment modalities including lubrication, contact lenses, and limbal stem cell
      transplantation are reviewed. CONCLUSIONS: The ophthalmic conditions seen in
      ectrodactyly-ectodermal dysplasia-cleft syndrome frequently lead to vision loss.
      Early correct diagnosis and appropriate therapy are paramount because p63 gene
      mutations have a critical role in maintaining the integrity of the ocular surface
      in the setting of limbal stem cell deficiency, especially if there are other
      ocular surface insults such as lid disease, meibomian gland dysfunction and
      toxicity from topical medications. Patients should be monitored at regular,
      frequent intervals; and particular attention should be taken to avoid adverse
      secondary effects of these conditions and medications.

PMID- 25769662
TI  - Age as a Prognostic Factor in Patients with Acute Coronary Syndrome undergoing
      Urgent/Emergency Cardiac Surgery.
AB  - BACKGROUND: Patients presenting with acute coronary syndrome (ACS) who require
      urgent/emergency coronary artery bypass grafting (CABG) are increasing, as is the
      complexity of their clinical characteristics, one of which is advanced age. We
      evaluated the prognostic role of age in patients undergoing urgent/emergency
      cardiac surgery for ACS. METHODS: From January to December 2013, 452 consecutive
      patients underwent CABG at our institution. Among these, 213 presented with ACS,
      were enrolled in the study and divided into tertiles of age: First: 40-65 years
      old (n=73), Second: 66-74 (n=70), Third: 75-89 (n=70). Patients were followed
      post-operatively for 30 days. RESULTS: No differences between tertiles were found
      for baseline clinical and angiographic characteristics. Off-pump interventions
      were 67.6%. Older patients more frequently required an associate intervention to
      CABG for a mechanical complication of ACS. Overall 30-day all-cause mortality was
      4.7% (n=10); 0.6% (n=1) in patients undergoing isolated CABG (n=168, 78.9%). The
      STEMI diagnosis was an independent risk factor for 30-day mortality, and age was
      not. CONCLUSIONS: The 30-day mortality rate of older ACS patients who undergo
      urgent/emergency CABG is comparable to that of younger ones. Pre-operative risk
      assessment should rely on evaluation of the clinical complexity of each patient
      independent of their chronological age, to customise the therapeutic strategy.

PMID- 25769663
TI  - Safety and Efficacy of Ventricular Septal Defect Repair Using a Cosmetic Shorter
      Right Lateral Thoracotomy on Infants Weighing Less than 5 kg.
AB  - OBJECTIVES: This study evaluated the safety and efficacy of a cosmetic right
      lateral thoracotomy for ventricular septal defect (VSD) repair in infants
      weighing less than 5 kg. METHODS: Eighty-nine infants who underwent a right
      lateral thoracotomy (right group) and 116 infants who underwent a median
      sternotomy (median group) were included. Patient characteristics, and
      perioperative and follow-up data were retrospectively analysed. RESULTS: Patient
      characteristics were comparable between the two groups as were cardiopulmonary
      bypass and aortic cross-clamping time, length of intensive care unit stay,
      ventilation duration and application of inotropic drugs. Compared to the median
      group, there was shorter procedure time (p < 0.05), shorter length of incision
      (p<0.05), and less drainage and transfusion in the right group (p<0.05). The peak
      airway pressure, partial oxygen pressure, partial carbon dioxide pressure,
      oxygenation index and alveolar-arterial oxygen gradients were similar for these
      two groups at the four time points analysed. No deaths occurred in either group
      and differences in morbidity were insignificant. No cardiac or thoracotomy
      related complications occurred within the 18.4 +/- 9.9 month follow-up.
      CONCLUSIONS: A right lateral thoracotomy reduces operative traumas and is as safe
      and effective as a median sternotomy at VSD repair in infants under 5 kg in
      weight.

PMID- 25769664
TI  - Epidemiology, antifungal susceptibilities, and risk factors for invasive
      candidiasis from 2011 to 2013 in a teaching hospital in southwest China.
AB  - BACKGROUND: Invasive candidiasis (IC) is the most common cause of invasive fungal
      infections. Identification of risk factors for such infection may help in the
      empirical therapeutic decision-making process. We conducted this study to
      characterize the clinical epidemiology of such infection and to differentiate
      risk factors between Candida albicans and Candida non-albicans species. METHODS:
      We retrospectively evaluated patients with IC from 2011 to 2013. Clinical data,
      antibiotic therapy, underlying condition, and invasive procedures were analyzed
      and compared between C. albicans and C. non-albicans species. RESULTS: C.
      albicans was the most frequently isolated Candida species (48.6% of all IC
      patients), although C. non-albicans spp. were more commonly isolated overall. C.
      albicans, Candida tropicalis, and Candida parapsilosis have a high susceptibility
      rate to all antifungal agents (>90%), whereas Candida glabrata showed decreased
      susceptibility to fluconazole and itraconazole. Amphotericin B demonstrated
      excellent antifungal activity against all Candida species. Univariate analyses
      showed that IC patients with C. albicans had a higher ratio of older age (p =
      0.008), solid tumor (p = 0.029), and hypoproteinemia (p = 0.019), whereas those
      with C. non-albicans spp. had a higher ratio of hospital length of stay (p =
      0.005), usage of corticosteroids (p = 0.011), duration on corticosteroids (p =
      0.005), chemotherapy (p = 0.022), hematologic malignancy (p = 0.039), neutropenia
      (p = 0.030), and usage of glycopeptides (p = 0.002). Multivariate analyses showed
      that a significant predictor of IC due to C. albicans was hypoproteinemia [odds
      ratio (95% confidence interval) = 2.133 (1.164-3.908), p = 0.014]. CONCLUSION: C.
      albicans was the most frequently isolated Candida species. The risk factors
      between C. albicans and C. non-albicans species are different.

PMID- 25769665
TI  - Comparison of Clostridium difficile isolates from individuals with recurrent and
      single episode of infection.
AB  - PURPOSE: Recurrent Clostridium difficile infection (CDI) is an increasing
      problem, yet reasons for this are poorly understood. Attention has been paid to
      the role of strain, with conflicting association of ribotype 027 and recurrences.
      METHODS: Stool samples and medical records data were collected from 60 patients:
      27 with recurrent CDI and 33 with single episode CDI. C. difficile was isolated
      and ribotyped, and minimum inhibitory concentrations of metronidazole and
      vancomycin were determined by Etest. RESULTS: Twenty-seven ribotypes were
      identified, but only four (027, 014 and two internally designated strains) were
      found in more than one patient. Ribotype 027 predominated and was significantly
      over-represented in the recurrent CDI group (70%) versus the single episode CDI
      group (30%) (P = 0.004). Female gender and the presence of ribotype 027 were
      significantly associated with recurrent CDI in the multivariable model.
      Metronidazole MICs for recurrent isolates were significantly higher compared to
      single episode isolates (P <= 0.024). A general linear model indicated that the
      difference in MIC was associated with ribotype 027 (P = 0.0023), not whether the
      isolate was from recurrent or single episode disease (P = 0.25). CONCLUSIONS:
      Ribotype 027 was associated with recurrent disease. While there was no difference
      in the prevalence of metronidazole resistance, isolates from recurrent CDI
      patients had significantly higher metronidazole MICs, because of higher MICs in
      ribotype 027. This study provides further support to the clinical importance of
      ribotype 027 and raises questions about the potential impact of decreased
      metronidazole susceptibility on the pathophysiology of recurrent CDI.

PMID- 25769666
TI  - Real-time contrast ultrasound muscle perfusion imaging with intermediate-power
      imaging coupled with acoustically durable microbubbles.
AB  - BACKGROUND: There is growing interest in limb contrast-enhanced ultrasound (CEU)
      perfusion imaging for the evaluation of peripheral artery disease. Because of low
      resting microvascular blood flow in skeletal muscle, signal enhancement during
      limb CEU is prohibitively low for real-time imaging. The aim of this study was to
      test the hypothesis that this obstacle can be overcome by intermediate- rather
      than low-power CEU when performed with an acoustically resilient microbubble
      agent. METHODS: Viscoelastic properties of Definity and Sonazoid were assessed by
      measuring bulk modulus during incremental increases in ambient pressure to 200 mm
      Hg. Comparison of in vivo microbubble destruction and signal enhancement at a
      mechanical index (MI) of 0.1 to 0.4 was performed by sequential reduction in
      pulsing interval from 10 to 0.05 sec during limb CEU at 7 MHz in mice and 1.8 MHz
      in dogs. Destruction was also assessed by broadband signal generation during
      passive cavitation detection. Real-time CEU perfusion imaging with destruction
      replenishment was then performed at 1.8 MHz in dogs using an MI of 0.1, 0.2, or
      0.3. RESULTS: Sonazoid had a higher bulk modulus than Definity (66 +/- 12 vs 29
      +/- 2 kPa, P = .02) and exhibited less inertial cavitation (destruction) at MIs
      >= 0.2. On in vivo CEU, maximal signal intensity increased incrementally with MI
      for both agents and was equivalent between agents except at an MI of 0.1 (60% and
      85% lower for Sonazoid at 7 and 1.8 MHz, respectively, P < .05). However, on
      progressive shortening of the pulsing interval, Definity was nearly completely
      destroyed at MIs >= 0.2 at 1.8 and 7 MHz, whereas Sonazoid was destroyed only at
      1.8 MHz at MIs >= 0.3. As a result, real-time CEU perfusion imaging demonstrated
      approximately fourfold greater enhancement for Sonazoid at an MI of 0.3 to 0.4.
      CONCLUSIONS: Robust signal enhancement during real-time CEU perfusion imaging of
      the limb is possible when using intermediate-power imaging coupled with a durable
      microbubble contrast agent.

PMID- 25769667
TI  - Bioanalytical insights into mediator lipidomics.
AB  - The importance of lipids in health and disease has been widely acknowledged.
      Lipids are well known to undergo enzymatic and/or non-enzymatic conversions to
      lipid mediators (LMs), which demonstrate potent actions in various biological
      events, such as the regulation of cellular signaling pathways and the promotion
      and resolution of inflammation. LMs activate G-protein-coupled receptors (GPCRs)
      to exert various functions. Monitoring these mediators in disease is essential to
      uncover the mechanisms of pathogenesis for many diseases, such as asthma,
      rheumatoid arthritis, Alzheimer's disease, and cancer. Along with technical
      developments in mass spectrometry, highly sensitive and multiplexed analyses of
      LMs in the human periphery and other tissues have become available. These
      advancements enable the temporal and spatial profiling of LMs; therefore, the
      findings obtained from LM profiling are expected to decode pathology. As trace
      amounts of LMs can exert functions, the development of a highly sensitive,
      accurate, and robust analytical method is necessary. Although not mandatory,
      mediator lipidomics validation is becoming popular and remains challenging.
      Because LMs already exist in biological matrices, evaluations of the matrix
      effect and extraction efficiencies are important issues. Thus, more careful
      analyses are required. In this review, we focus on mediator lipidomics, including
      polyunsaturated fatty acids (PUFAs), such as omega-3 and omega-6 fatty acids, and
      LMs derived from PUFAs, such as eicosanoids, lipoxins and resolvins. In addition
      to the recent progress in human mediator lipidomics, bioanalytical insights
      derived from this field (i.e., effective sample preparation from biological
      matrices and evaluation of the matrix effect) are described herein. 

PMID- 25769668
TI  - Induced circular dichroism as a tool to investigate the binding of drugs to
      carrier proteins: Classic approaches and new trends.
AB  - Induced circular dichroism (ICD) is a spectroscopic phenomenon that provides
      versatile and useful methods for characterizing the structural and dynamic
      properties of the binding of drugs to target proteins. The understanding of
      biorecognition processes at the molecular level is essential to discover and
      validate new pharmacological targets, and to design and develop new potent and
      selective drugs. The present article reviews the main applications of ICD to drug
      binding studies on serum carrier proteins, going from the classic approaches for
      the derivation of drug binding parameters and the identification of binding
      sites, to an overview of the emerging trends for the characterization of binding
      modes by means of quantum chemical (QC) techniques. The advantages and limits of
      the ICD methods for the determination of binding parameters are critically
      reviewed; the capability to investigate the binding interactions of drugs and
      metabolites to their target proteins is also underlined, as well as the
      possibility of characterizing the binding sites to obtain a complete picture of
      the binding mechanism and dynamics. The new applications of ICD methods to
      identify stereoselective binding modes of drug/protein complexes are then
      reviewed with relevant examples. The combined application of experimental ICD
      spectroscopy and QC calculations is shown to identify qualitatively the bound
      conformations of ligands to target proteins even in the absence of a detailed
      structure of the binding sites, either obtained from experimental X-ray
      crystallography and NMR measurements or from computational models of the complex.

PMID- 25769669
TI  - Inhibitory control of site-specific synaptic plasticity in a model CA1 pyramidal
      neuron.
AB  - A computational model of a biochemical network underlying synaptic plasticity is
      combined with simulated on-going electrical activity in a model of a hippocampal
      pyramidal neuron to study the impact of synapse location and inhibition on
      synaptic plasticity. The simulated pyramidal neuron is activated by the realistic
      stimulation protocol of causal and anticausal spike pairings of presynaptic and
      postsynaptic action potentials in the presence and absence of spatially targeted
      inhibition provided by basket, bistratified and oriens-lacunosum moleculare (OLM)
      interneurons. The resulting Spike-timing-dependent plasticity (STDP) curves
      depend strongly on the number of pairing repetitions, the synapse location and
      the timing and strength of inhibition. 

PMID- 25769670
TI  - Genetic project calls for 100,000 volunteers from Pakistani and Bangladeshi
      communities in east London.

PMID- 25769671
TI  - The 26-Minute Laparoscopic Sacral Colpopexy: Do We Really Need Robotic
      Technology?
AB  - STUDY OBJECTIVES: To demonstrate the technical steps of a laparoscopic sacral
      colpopexy (LSC), demonstrate the efficiency of LSC, review the comparative LSC
      and robotic-assisted sacral colpopexy (RSC) literature, and challenge surgeons'
      conventional wisdom regarding RSC. DESIGN: Use of a time-stamped video with a
      step-by-step explanation of the technique and slides of comparative trials and
      benefits of robotic surgery. SETTING: Sacral colpopexy remains the gold standard
      surgical procedure for treating vaginal vault prolapse. It can be performed via
      laparotomy, laparoscopically with or without robotic assistance. Robotic
      technology has been marketed based on unsubstantiated claims, including better
      visualization, smaller incisions, less blood loss, and greater efficiency.
      Conventional wisdom suggests that robotic-assisted laparoscopic surgery is easier
      and thus faster for the practicing surgeon. INTERVENTION: A time-stamped video of
      LSC in a woman with vaginal vault prolapse was performed in 26 minutes using 14
      sutures in the vagina and 2 sutures in the presacral ligament. The stopwatch
      began after placement of the scope in the abdomen and before placement of the 3
      accessory posts and ended with peritoneal closure over the sacral colpopexy mesh.
      The patient signed a consent and release form for the use of her video for
      educational purposes. CONCLUSION: A review of the literature suggests that the
      average RSC takes 260 minutes; the average is 200 minutes with the conventional
      LSC technique, realizing a time savings of at least 60 minutes. Our 26-minute LSC
      supports this finding.

PMID- 25769673
TI  - Effect of anterior cervical osteophyte in poststroke dysphagia: a case-control
      study.
AB  - OBJECTIVE: To investigate whether the concomitant presence of anterior cervical
      osteophytes can influence the severity and outcome of patients with poststroke
      dysphagia. DESIGN: Retrospective case-control study. SETTING: Hospital.
      PARTICIPANTS: A total of 40 participants were identified (N=40). Patients with
      poststroke dysphagia with anterior cervical osteophytes (n=20) were identified
      and matched by age, sex, location, and laterality of the stroke lesion to a
      poststroke dysphagia control group with no anterior cervical osteophytes (n=20).
      INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Videofluoroscopic
      swallowing study, Functional Oral Intake Scale (FOIS), and Penetration-Aspiration
      Scale results assessed within the first month of stroke were analyzed. The FOIS
      at 6 months was recorded, and severity of dysphagia was compared between the 2
      groups. RESULTS: The case group had larger degrees of postswallow residues in the
      valleculae and pyriform sinuses (P=.020 and P<.001, respectively), with more
      patients showing postswallow aspiration (62.5%) than the control group (0%;
      P<.001), along with a higher risk of being on enteral nutrition feeding (odds
      ratio [OR]=13.933; 95% confidence interval [CI], 2.863-infinity) within the first
      month of stroke. At the 6-month follow-up, the case group had significantly lower
      mean FOIS scores (3.8+/-1.7) than the control group (6.1+/-1.3; P<.001), with an
      increased risk of having persistent dysphagia (OR=15.375; 95% CI, 3.195
      infinity). CONCLUSIONS: The presence of anterior cervical osteophytes, which may
      cause mechanical obstruction and interfere with residue clearance at the
      valleculae and pyriform sinuses and result in more postswallow aspiration, may
      influence initial severity and outcome of poststroke dysphagia. The presence of
      anterior cervical osteophytes may be considered an important clinical condition
      that may affect poststroke dysphagia rehabilitation.

PMID- 25769672
TI  - Perspective: a dynamics-based classification of ventricular arrhythmias.
AB  - Despite key advances in the clinical management of life-threatening ventricular
      arrhythmias, culminating with the development of implantable cardioverter
      defibrillators and catheter ablation techniques, pharmacologic/biologic
      therapeutics have lagged behind. The fundamental issue is that biological targets
      are molecular factors. Diseases, however, represent emergent properties at the
      scale of the organism that result from dynamic interactions between multiple
      constantly changing molecular factors. For a pharmacologic/biologic therapy to be
      effective, it must target the dynamic processes that underlie the disease. Here
      we propose a classification of ventricular arrhythmias that is based on our
      current understanding of the dynamics occurring at the subcellular, cellular,
      tissue and organism scales, which cause arrhythmias by simultaneously generating
      arrhythmia triggers and exacerbating tissue vulnerability. The goal is to create
      a framework that systematically links these key dynamic factors together with
      fixed factors (structural and electrophysiological heterogeneity) synergistically
      promoting electrical dispersion and increased arrhythmia risk to molecular
      factors that can serve as biological targets. We classify ventricular arrhythmias
      into three primary dynamic categories related generally to unstable Ca cycling,
      reduced repolarization, and excess repolarization, respectively. The clinical
      syndromes, arrhythmia mechanisms, dynamic factors and what is known about their
      molecular counterparts are discussed. Based on this framework, we propose a
      computational-experimental strategy for exploring the links between molecular
      factors, fixed factors and dynamic factors that underlie life-threatening
      ventricular arrhythmias. The ultimate objective is to facilitate drug development
      by creating an in silico platform to evaluate and predict comprehensively how
      molecular interventions affect not only a single targeted arrhythmia, but all
      primary arrhythmia dynamics categories as well as normal cardiac excitation
      contraction coupling. 

PMID- 25769675
TI  - Would Sherlock Holmes agree with our definition of rational polytherapy? A
      proposal for a national data bank on patients with epilepsy.

PMID- 25769674
TI  - Ictal body turning in focal epilepsy.
AB  - Despite the explanations of many lateralization findings, body turning in focal
      epilepsy has been rarely investigated. One of the aims of this study was to
      evaluate the role of ictal body turning in the lateralization of focal
      epilepsies. The records of 263 patients with focal epilepsy (temporal lobe
      epilepsy (TLE), n=178; extratemporal lobe epilepsy (ETLE), n=85) who underwent
      prolonged video-EEG monitoring during presurgical epilepsy evaluation were
      reviewed. Preoperative findings (TLE, n=16; ETLE, n=6) and postoperative outcomes
      (TLE, n=7) of patients with focal epilepsy with ictal body turning were assessed.
      For the evaluation of ictal body turning, two definitions were proposed.
      Nonversive body turning (NVBT) was used to denote at least a 90 degrees 
      nonforced (without tonic or clonic component) rotation of the upper (shoulder)
      and lower (hip) parts of the body around the body axis for a minimum of 3s.
      Versive body turning (VBT) was used to denote at least a 90 degrees  forced (with
      tonic or clonic component) rotation of the upper (shoulder) and lower (hip) parts
      of the body around the body axis for a minimum of 3s. Nonversive body turning was
      observed in 6% (n=11) of patients with TLE and 2% (n=2) of patients with ETLE.
      For VBT, these ratios were 5% (n=8) and 7% (n=6) for patients with TLE and ETLE,
      respectively. Nonversive body turning was frequently oriented to the same side as
      the epileptogenic zone (EZ) in TLE and ETLE seizures (76% and 80%, respectively).
      If the amount of NVBT was greater than 180 degrees , then it was 80% to the same
      side in TLE seizures. Versive body turning was observed in 86% of the TLE
      seizures, and 55% of the ETLE seizures were found to be contralateral to the EZ.
      When present with head turning, NVBT ipsilateral to the EZ and VBT contralateral
      to the EZ were more valuable for lateralization. In TLE seizures, a significant
      correlation was found between the head turning and body turning onsets and
      durations. Our study demonstrated that ictal body turning is a rarely observed
      but reliable lateralization finding in TLE and ETLE seizures, which also probably
      has the same pathophysiological mechanism as head turning in TLE seizures. 

PMID- 25769676
TI  - Partner loyalty is linked to reduced spread of disease in sex workers and in
      cattle, computational research shows.

PMID- 25769677
TI  - Molecular cloning, characterization and mRNA expression of duck interleukin-17F.
AB  - Interleukin-17F (IL-17F) is a proinflammatory cytokine that plays an important
      role in gut homeostasis. A full-length duck IL-17F (duIL-17F) cDNA with a 510-bp
      coding region was identified in ConA-activated splenic lymphocytes. duIL-17F is
      predicted to encode 166 amino acids, including a 26-amino acid signal peptide, a
      single N-linked glycosylation site, and six cysteine residues that are conserved
      in mammalian IL-17. duIL-17F shares 77.5% amino acid sequence identity with
      chicken IL-17F (chIL-17F), 37-46% with corresponding mammalian homologues, and
      53.5% with the previously described duck IL-17A (duIL-17A). The duIL-17F
      transcripts were expressed in a wide range of untreated tissues; levels were
      highest in the liver and moderate in the thymus, bursa, kidney, and intestinal
      tissues. Expression levels of duIL-17F transcript were slightly up-regulated in
      ConA- and LPS-activated splenic lymphocytes but not in poly I:C stimulated cells.
      duIL-17F forms heterodimers with duIL-17A. Recombinant duIL-17F, like duIL-17A,
      induced IL-1beta, IL-6, and IL-8 expression in duck embryonic fibroblasts (DEFs).
      duIL-17A, but not duIL-17F expression, was significantly up-regulated in the
      liver and spleen of Salmonella Typhimurium-infected ducks. Further analysis of
      the contributions of IL-17F to different Salmonella spp. or other disease models
      will be required to expand our understanding of its biological functions. 

PMID- 25769678
TI  - Comparison of the effect of total conservative parotidectomy versus superficial
      parotidectomy in management of benign parotid gland tumor: A systematic review.
AB  - PURPOSE: Since of the 1940s, there has been wide controversy about the most
      effective surgical treatment for the primary benign parotid tumor. This review
      investigates the effectiveness and associated complications of superficial
      parotidectomy versus total conservative parotidectomy in the management of
      primary benign parotid tumors. MATERIAL AND METHODS: An electronic search with
      restricted dates (1920-2014) and restricted language was performed in August
      2014. Thirteen studies were included. In total, 2477 patients were enrolled in
      the 13 studies, with 1317 patients undergoing superficial parotidectomy and 391
      patients undergoing total conservative parotidectomy; 769 patients treated with
      other surgical techniques were excluded. The maximum follow-up period varied
      between 2 and 24 years (mean 2.8 years). RESULTS: The incidence of recurrence in
      the superficial parotidectomy patients ranged from 0% to 15% (mean 5.7%),
      whereas, in the total conservative parotidectomy patients it ranged from 0% to
      16% (mean 3.03%). The incidence of the facial nerve paresis according to
      collected data in the superficial parotidectomy group ranged from 0% to 23% (mean
      6.75%), whereas in the total conservative parotidectomy group it was 0%-45% (mean
      15%). The incidence of facial nerve paralysis in the superficial parotidectomy
      group ranged from 0% to 3% (mean 0.8%), whereas in the total conservative
      parotidectomy group it was 0%-17 % (mean 4.4%). CONCLUSION: The results of this
      review suggest that superficial parotidectomy is superior to total conservative
      parotidectomy in the management of primary benign tumor in superficial lobes. In
      addition, superficial parotidectomy showed a minimal recurrence rate for benign
      tumor in superficial lobes.

PMID- 25769679
TI  - Chitosan based micro- and nanoparticles for colon-targeted delivery of vancomycin
      prepared by alternative processing methods.
AB  - The aim of this work was to prepare chitosan (CH) based particulate formulations
      for colon delivery of vancomycin (VM). Chitosan microparticles (MPs) and
      nanoparticles (NPs) loaded with VM were prepared using different
      CH/tripolyphosphate (TPP) molar ratios and different technological processes. In
      particular, nanoparticles were prepared by ionic gelation and freeze-drying to
      recover these particles, or, alternatively, by spray-drying method.
      Microparticles were prepared using a different spray-dryer. Micro- and
      nanoparticles were characterized in terms of size distributions by photon
      correlation spectroscopy (PCS), while encapsulation and drug loading efficiencies
      were studied using a dialysis method. Fourier Transform Infrared Spectroscopy (FT
      IR) was employed to determine the surface composition of the micro- and
      nanoparticles respectively, and the morphologies of the developed systems were
      studied by scanning electron microscopy (SEM). Water uptake as well as drug
      release profiles were also measured. Antibacterial activity against
      Staphylococcus aureus, a Gram-positive model strain, was evaluated. FT-IR results
      suggested an electrostatic interaction between VM and CH/TPP particles. Moreover,
      the particles were found to hold a positive zeta-potential, indicating the
      presence of CH on the particle surfaces. Particle size and encapsulation
      efficiency were mainly influenced by the different manufacturing processes
      employed. Nanoparticles obtained by spray-drying showed the best results in terms
      of water uptake and drug release rate. Moreover, they showed a good bactericidal
      activity against S. aureus. 

PMID- 25769680
TI  - Influence of small amorphous amounts in hydrophilic and hydrophobic APIs on
      storage stability of dry powder inhalation products.
AB  - The effects of different manufacturing methods to induce formation of amorphous
      content, changes of physico-chemical characteristics of powder blends and changes
      of aerodynamic properties over storage time (6months) analyzed with the Next
      Generation Impactor (NGI) are investigated. Earlier studies have shown that
      standard pharmaceutical operations lead to structural disorders which may
      influence drug delivery and product stability. In this investigation, fully
      amorphous drug samples produced by spray-drying (SD) and ball-milling (BM) as
      well as semi-crystalline samples (produced by blending and micronization) are
      studied and compared to fully crystalline starting material. The amorphous
      content of these hydrophilic and hydrophobic active pharmaceutical ingredients
      (APIs) was determined using a validated one-step DVS-method. For the conducted
      blending and micronization tests, amorphous amounts up to a maximum of 5.1% for
      salbutamol sulfate (SBS) and 17.0% for ciclesonide (CS) were measured. In order
      to investigate the impact of small amorphous amounts, inhalable homogenous powder
      mixtures with very high and low amorphous content and a defined particle size
      were prepared with a Turbula blender for each API. These blends were stored
      (6months, 45% RH, room temperature) to evaluate the influence of amorphous
      amounts on storage stability. The fine particle fraction (FPF: % of emitted
      dose<5MUm) was determined with the NGI at defined time points. The amorphous
      amounts showed a major effect on dispersion behavior, the mixtures of the two
      APIs showed differences at the beginning of the study and significant differences
      in storage stability. The FPF values for SBS decreased during storage (FPF: from
      35% to <27%) for the blend with high amorphous amounts, in contrast the initially
      re-crystallized sample achieved a comparable constant level of about 25%. For the
      hydrophobic CS a constantly increasing FPF (from 6% to >15%) over storage time
      for both types of blends was determined. Therefore, prolonged stability of
      amorphous parts and an incalculable behavior for CS blends are supposed, in
      contrast, SBS showed a controllable FPF after conditioning. 

PMID- 25769681
TI  - Enriched inorganic compounds in diesel exhaust particles induce mitogen-activated
      protein kinase activation, cytoskeleton instability, and cytotoxicity in human
      bronchial epithelial cells.
AB  - This study assessed the effects of the diesel exhaust particles on ERK and JNK
      MAPKs activation, cell rheology (viscoelasticity), and cytotoxicity in bronchial
      epithelial airway cells (BEAS-2B). Crude DEP and DEP after extraction with hexane
      (DEP/HEX) were utilized. The partial reduction of some DEP/HEX organics increased
      the biodisponibility of many metallic elements. JNK and ERK were activated
      simultaneously by crude DEP with no alterations in viscoelasticity of the cells.
      Mitochondrial activity, however, revealed a decrease through the MTT assay.
      DEP/HEX treatment increased viscoelasticity and cytotoxicity (membrane damage),
      and also activated JNK. Our data suggest that the greater bioavailability of
      metals could be involved in JNK activation and, consequently, in the reduction of
      fiber coherence and increase in the viscoelasticity and cytotoxicity of BEAS
      cells. The adverse findings detected after exposure to crude DEP and to DEP/HEX
      reflect the toxic potential of diesel compounds. Considering the fact that the
      cells of the respiratory epithelium are the first line of defense between the
      body and the environment, our data contribute to a better understanding of the
      pathways leading to respiratory cell injury and provide evidence for the onset of
      or worsening of respiratory diseases caused by inorganic compounds present in
      DEP. 

PMID- 25769682
TI  - Case-based reasoning using electronic health records efficiently identifies
      eligible patients for clinical trials.
AB  - OBJECTIVE: To develop a cost-effective, case-based reasoning framework for
      clinical research eligibility screening by only reusing the electronic health
      records (EHRs) of minimal enrolled participants to represent the target patient
      for each trial under consideration. MATERIALS AND METHODS: The EHR data-
      specifically diagnosis, medications, laboratory results, and clinical notes--of
      known clinical trial participants were aggregated to profile the "target patient"
      for a trial, which was used to discover new eligible patients for that trial. The
      EHR data of unseen patients were matched to this "target patient" to determine
      their relevance to the trial; the higher the relevance, the more likely the
      patient was eligible. Relevance scores were a weighted linear combination of
      cosine similarities computed over individual EHR data types. For evaluation, we
      identified 262 participants of 13 diversified clinical trials conducted at
      Columbia University as our gold standard. We ran a 2-fold cross validation with
      half of the participants used for training and the other half used for testing
      along with other 30 000 patients selected at random from our clinical database.
      We performed binary classification and ranking experiments. RESULTS: The overall
      area under the ROC curve for classification was 0.95, enabling the highlight of
      eligible patients with good precision. Ranking showed satisfactory results
      especially at the top of the recommended list, with each trial having at least
      one eligible patient in the top five positions. CONCLUSIONS: This relevance-based
      method can potentially be used to identify eligible patients for clinical trials
      by processing patient EHR data alone without parsing free-text eligibility
      criteria, and shows promise of efficient "case-based reasoning" modeled only on
      minimal trial participants.

PMID- 25769683
TI  - Success criteria for electronic medical record implementations in low-resource
      settings: a systematic review.
AB  - OBJECTIVE: Electronic medical record (EMR) systems have the potential of
      supporting clinical work by providing the right information at the right time to
      the right people and thus make efficient use of resources. This is especially
      important in low-resource settings where reliable data are also needed to support
      public health and local supporting organizations. In this systematic literature
      review, our objectives are to identify and collect literature about success
      criteria of EMR implementations in low-resource settings and to summarize them
      into recommendations. MATERIALS AND METHODS: Our search strategy relied on PubMed
      queries and manual bibliography reviews. Studies were included if EMR
      implementations in low-resource settings were described. The extracted success
      criteria and measurements were summarized into 7 categories: ethical, financial,
      functionality, organizational, political, technical, and training. RESULTS: We
      collected 381 success criteria with 229 measurements from 47 articles out of 223
      articles. Most papers were evaluations or lessons learned from African countries,
      published from 1999 to 2013. Almost half of the EMR systems served a specific
      disease area like human immunodeficiency virus (HIV). The majority of criteria
      that were reported dealt with the functionality, followed by organizational
      issues, and technical infrastructures. Sufficient training and skilled personnel
      were mentioned in roughly 10%. Political, ethical, and financial considerations
      did not play a predominant role. More evaluations based on reliable frameworks
      are needed. CONCLUSIONS: Highly reliable data handling methods, human resources
      and effective project management, as well as technical architecture and
      infrastructure are all key factors for successful EMR implementation.

PMID- 25769684
TI  - Standard for improving emergency information interoperability: the HL7 data
      elements for emergency department systems.
AB  - BACKGROUND: Emergency departments in the United States service over 130 million
      visits per year. The demands for information from these visits require
      interoperable data exchange standards. While multiple data exchange
      specifications are in use, none have undergone rigorous standards review. This
      paper describes the creation and balloting of the Health Level Seven (HL7) Data
      Elements for Emergency Department Systems (DEEDS). METHODS: Existing data
      exchange specifications were collected and organized into categories reflecting
      the workflow of emergency care. The concepts were then mapped to existing
      standards for vocabulary, data types, and the HL7 information model. The HL7
      community then processed the specification through the normal balloting process
      addressing all comments and concerns. The resulting specification was then
      submitted for publication as an HL7 informational standard. RESULTS: The
      resulting specification contains 525 concepts related to emergency care required
      for operations and reporting to external agencies. An additional 200 of the most
      commonly ordered laboratory tests were included. Each concept was given a unique
      identifier and mapped to Logical Observation Identifiers, Names, and Codes
      (LOINC). HL7 standard data types were applied. DISCUSSION: The HL7 DEEDS
      specification represents the first set of common ED related data elements to
      undergo rigorous standards development. The availability of this standard will
      contribute to improved interoperability of emergency care data.

PMID- 25769685
TI  - Leveraging the NLM map from SNOMED CT to ICD-10-CM to facilitate adoption of ICD
      10-CM.
AB  - OBJECTIVE: Develop and test web services to retrieve and identify the most
      precise ICD-10-CM code(s) for a given clinical encounter. Facilitate creation of
      user interfaces that 1) provide an initial shortlist of candidate codes, ideally
      visible on a single screen; and 2) enable code refinement. MATERIALS AND METHODS:
      To satisfy our high-level use cases, the analysis and design process involved
      reviewing available maps and crosswalks, designing the rule adjudication
      framework, determining necessary metadata, retrieving related codes, and
      iteratively improving the code refinement algorithm. RESULTS: The Partners ICD-10
      CM Search and Mapping Services (PI-10 Services) are SOAP web services written
      using Microsoft's.NET 4.0 Framework, Windows Communications Framework, and SQL
      Server 2012. The services cover 96% of the Partners problem list subset of SNOMED
      CT codes that map to ICD-10-CM codes and can return up to 76% of the 69,823
      billable ICD-10-CM codes prior to creation of custom mapping rules. DISCUSSION:
      We consider ways to increase 1) the coverage ratio of the Partners problem list
      subset of SNOMED CT codes and 2) the upper bound of returnable ICD-10-CM codes by
      creating custom mapping rules. Future work will investigate the utility of the
      transitive closure of SNOMED CT codes and other methods to assist in custom rule
      creation and, ultimately, to provide more complete coverage of ICD-10-CM codes.
      CONCLUSIONS: ICD-10-CM will be easier for clinicians to manage if applications
      display short lists of candidate codes from which clinicians can subsequently
      select a code for further refinement. The PI-10 Services support ICD-10 migration
      by implementing this paradigm and enabling users to consistently and accurately
      find the best ICD-10-CM code(s) without translation from ICD-9-CM.

PMID- 25769686
TI  - Paper versus EHR: simplistic comparisons may not capture current reality.

PMID- 25769687
TI  - The design of pH-sensitive chitosan-based formulations for gastrointestinal
      delivery.
AB  - Chitosan, a nontoxic and biocompatible polysaccharide, has been widely explored
      for the gastrointestinal delivery of drugs, proteins, peptides and genes for
      different therapeutic purposes. Because a pH gradient exists in the
      gastrointestinal tract, chitosan-based formulations in response to specific pH
      conditions, such as the low pH in the stomach and a high pH in the intestine,
      have been developed as a general strategy for disease diagnosis and therapy.
      Tailored pH-responsive drug release in the gastrointestinal tract can be achieved
      with various chitosan-based formulations such as nanoparticles, microspheres,
      hydrogels and nanocomposites. This review focuses on the most recent development
      of chitosan-based pH-sensitive formulations for gastrointestinal delivery,
      covering various types of chitosan-based formulations, their pH-responsive
      mechanisms and biomedical applications. 

PMID- 25769688
TI  - A convergent uptake route for peptide- and polymer-based nucleotide delivery
      systems.
AB  - Cell-penetrating peptides (CPPs) have been used as vehicles to deliver various
      cargos into cells and are promising as tools to deliver therapeutic biomolecules
      such as oligonucleotides both in vitro and in vivo. CPPs are positively charged
      and it is believed that CPPs deliver their cargo in a receptor-independent manner
      by interacting with the negatively charged plasma membrane and thereby inducing
      endocytosis. In this study we examine the mechanism of uptake of several
      different, well known, CPPs that form complexes with oligonucleotides. We show
      that these CPP:oligonucleotide complexes are negatively charged in transfection
      media and their uptake is mediated by class A scavenger receptors (SCARA). These
      receptors are known to promiscuously bind to, and mediate uptake of poly-anionic
      macromolecules. Uptake of CPP:oligonucleotide complexes was abolished using
      pharmacological SCARA inhibitors as well as siRNA-mediated knockdown of SCARA.
      Additionally, uptake of CPP:oligonucleotide was significantly increased by
      transiently overexpressing SCARA. Furthermore, SCARA inhibitors also blocked
      internalization of cationic polymer:oligonucleotide complexes. Our results
      demonstrate that the previous held belief that CPPs act receptor independently
      does not hold true for CPP:oligonucleotide complexes, as scavenger receptor class
      A (SCARA) mediates the uptake of all the examined CPP:oligonucleotide complexes
      in this study. 

PMID- 25769689
TI  - Expression of Lactococcus lactis NADH oxidase increases 2,3-butanediol production
      in Pdc-deficient Saccharomyces cerevisiae.
AB  - To minimize glycerol production during 2,3-BD fermentation by the engineered
      Saccharomyces cerevisiae, the Lactococcus lactis water-forming NADH oxidase gene
      (noxE) was expressed at five different levels. The expression of NADH oxidase
      substantially decreased the intracellular NADH/NAD(+) ratio. The S. cerevisiae
      BD5_T2nox strain expressing noxE produced 2,3-BD with yield of 0.359 g 2,3
      BD/gglucose and glycerol with 0.069gglycerol/gglucose, which are 23.8% higher and
      65.3% lower than those of the isogenic strain without noxE. These results
      demonstrate that the carbon flux could be redirected from glycerol to 2,3-BD
      through alteration of the NADH/NAD(+) ratio by the expression of NADH oxidase.

PMID- 25769690
TI  - In situ transesterification of highly wet microalgae using hydrochloric acid.
AB  - This study addresses in situ transesterification of highly wet microalgae with
      hydrochloric acid (HCl) as a catalyst. In situ transesterification was performed
      by heating the mixture of wet algal cells, HCl, methanol, and solvent in one pot,
      resulting in the fatty acid methyl ester (FAME) yield over 90% at 95 degrees C.
      The effects of reaction variables of temperature, amounts of catalyst, reactant,
      and solvent, and type of solvents on the yield were investigated. Compared with
      the catalytic effect of H2SO4, in situ transesterification using HCl has benefits
      of being less affected by moisture levels that are as high as or above 80%, and
      requiring less amounts of catalyst and solvent. For an equimolar amount of
      catalyst, HCl showed 15wt.% higher FAME yield than H2SO4. This in situ
      transesterification using HCl as a catalyst would help to realize a feasible way
      to produce biodiesel from wet microalgae. 

PMID- 25769691
TI  - Synergistic effect of fermentable and non-fermentable carbon sources enhances TAG
      accumulation in oleaginous yeast Rhodosporidium kratochvilovae HIMPA1.
AB  - Novel strategy for enhancing TAG accumulation by simultaneous utilization of
      fermentable and non-fermentable carbon sources as substrate for cultivation of
      oleaginous yeast Rhodosporidium kratochvilovae HIMPA1 were undertaken in this
      investigation. The yeast strain showed direct correlation between the size of
      lipid bodies, visualized by BODIPY stain (493-515 nm) and TAG accumulation when
      examined on individual fermenting and non-fermenting carbon sources and their
      mixtures. Maximum TAG accumulation (MUm) in glucose (2.38 +/- 0.52), fructose
      (4.03 +/- 0.38), sucrose (4.24 +/- 0.45), glycerol (4.35 +/- 0.54), xylulose
      (3.94 +/- 0.12), and arabinose (2.98 +/- 0.43) were observed. Synergistic effect
      of the above carbon sources (fermentable and non-fermentable) in equimolar
      concentration revealed maximum lipid droplet size of 5.35 +/- 0.76 MUm and cell
      size of 6.89 +/- 0.97 MUm. Total lipid content observed in mixed carbon sources
      was 9.26 g/l compared to glucose (6.2g/l). FAME profile revealed enhanced longer
      chain (C14:0-C24:0) fatty acids in mix carbon sources.

PMID- 25769692
TI  - The activation of protein homeostasis protective mechanisms perhaps is not
      responsible for lifespan extension caused by deficiencies of mitochondrial
      proteins in C. elegans.
AB  - During aging the ability of organisms to maintain the protein homeostasis
      declines and damaged and misfolded proteins accumulate in cells. But whether the
      deterioration of protein homeostasis is the cause or consequence of aging is not
      clearly understood. Mitochondrial dysfunctions usually lead to increased
      longevity in Caenorhabditis elegans, the cause of which is believed to be the
      activation of protein homeostasis protective mechanisms including mitochondrial
      unfolded protein response (UPR(mt)) and GCN-2 kinase mediated nutrient-sensing
      pathway. However, we investigated four genes which encode well-defined
      mitochondrial proteins and found that: (i) UPR(mt) activation was associated with
      not only increased longevity by knockdown of mfn-1, cco-1, or nuo-6, but also
      decreased longevity by mev-1 RNAi; (ii) The blockage of UPR(mt) pathway did not
      repress mfn-1, cco-1, or nuo-6 RNAi induced lifespan extension; (iii) The
      activation of UPR(mt) did not increase longevity; (iv) Knockdown of mfn-1, cco-1,
      or nuo-6 increased longevity independently of GCN-2. The combined results
      indicate that two important kinds of the protein homeostasis protective
      mechanisms, namely UPR(mt) and GCN-2 pathways, are not responsible for
      mitochondrial deficiency induced lifespan extension. The enhanced protection of
      protein homeostasis may be insufficient to slow aging, and there may be other
      mechanisms that contribute to the increased longevity in response to
      mitochondrial dysfunctions. 

PMID- 25769693
TI  - Reconceptualising public acceptability: A study of the ways people respond to
      policies aimed to reduce alcohol consumption.
AB  - The issue of public acceptability of health policies is key if they are to have
      significant and lasting impact. This study, based on focus groups conducted in
      England, examines the ways people responded to, and made sense of, policy ideas
      aimed at reducing alcohol consumption. Although effective policies were supported
      in the abstract, specific proposals were consistently rejected because they were
      not thought to map onto the fundamental causes of excessive drinking, which was
      not attributed to alcohol itself but instead its cultural context. Rather than
      being influenced by the credibility of evidence, or assessed according to likely
      gains set against possible losses, such responses were established dynamically as
      people interacted with others to make sense of the topic. This has significant
      implications for policy-makers, suggesting that existing beliefs and knowledge
      need to be taken into account as potentially productive rather than obstructive
      resources.

PMID- 25769694
TI  - Proud2Bme: Exploratory research on care and control in young women's online
      eating disorder narratives.
AB  - Illness narratives have been studied to understand the patient's point of view.
      These narratives are becoming more prolific, accessible, and specialized, thanks
      to the improved Internet access and the growth of health-specific online
      communities. This article analyses illness narratives posted on a Dutch eating
      disorder website hosted by a treatment centre. Specifically, we look at 'care of
      the self' and 'control'. The young women wrote about controlling situations with
      disordered eating as a self-care tool, about being controlled by the disorder and
      about regaining control over the disorder. The website, with the opportunity for
      constant, unseen supervision, coercion through comments, and steering through
      edits and comments, revealed various modalities of control. While issues of
      control and eating disorders have been explored by others, little work has been
      done on how the control experienced by the young women (coercion on the
      individual, the body as the object of control, and the modality of pressure and
      supervision) interact, how control is presented in stories for a recovery
      focused, monitored website, and how the website directs the content. As recovery
      focused, therapist-led website is likely to continue growing, understanding how
      and why young women talk about care and control in the context of such websites
      is an important topic.

PMID- 25769695
TI  - Rest represses maturation within migrating facial branchiomotor neurons.
AB  - The vertebrate brain arises from the complex organization of millions of neurons.
      Neurogenesis encompasses not only cell fate specification from neural stem cells,
      but also the terminal molecular and morphological maturation of neurons at
      correct positions within the brain. RE1-silencing transcription factor (Rest) is
      expressed in non-neural tissues and neuronal progenitors where it inhibits the
      terminal maturation of neurons by repressing hundreds of neuron-specific genes.
      Here we show that Rest repression of maturation is intimately linked with the
      migratory capability of zebrafish facial branchiomotor neurons (FBMNs), which
      undergo a characteristic tangential migration from hindbrain rhombomere (r) 4 to
      r6/r7 during development. We establish that FBMN migration is increasingly
      disrupted as Rest is depleted in zebrafish rest mutant embryos, such that around
      two-thirds of FBMNs fail to complete migration in mutants depleted of both
      maternal and zygotic Rest. Although Rest is broadly expressed, we show that de
      repression or activation of Rest target genes only within FBMNs is sufficient to
      disrupt their migration. We demonstrate that this migration defect is due to
      precocious maturation of FBMNs, based on both morphological and molecular
      criteria. We further show that the Rest target gene and alternative splicing
      factor srrm4 is a key downstream regulator of maturation; Srrm4 knockdown
      partially restores the ability of FBMNs to migrate in rest mutants while
      preventing their precocious morphological maturation. Rest must localize to the
      nucleus to repress its targets, and its subcellular localization is highly
      regulated: we show that targeting Rest specifically to FBMN nuclei rescues FBMN
      migration in Rest-deficient embryos. We conclude that Rest functions in FBMN
      nuclei to inhibit maturation until the neurons complete their migration. 

PMID- 25769696
TI  - Explosive tandem and segmental duplications of multigenic families in Eucalyptus
      grandis.
AB  - Plant organisms contain a large number of genes belonging to numerous multigenic
      families whose evolution size reflects some functional constraints. Sequences
      from eight multigenic families, involved in biotic and abiotic responses, have
      been analyzed in Eucalyptus grandis and compared with Arabidopsis thaliana. Two
      transcription factor families APETALA 2 (AP2)/ethylene responsive factor and
      GRAS, two auxin transporter families PIN-FORMED and AUX/LAX, two oxidoreductase
      families (ascorbate peroxidases [APx] and Class III peroxidases [CIII Prx]), and
      two families of protective molecules late embryogenesis abundant (LEA) and DNAj
      were annotated in expert and exhaustive manner. Many recent tandem duplications
      leading to the emergence of species-specific gene clusters and the explosion of
      the gene numbers have been observed for the AP2, GRAS, LEA, PIN, and CIII Prx in
      E. grandis, while the APx, the AUX/LAX and DNAj are conserved between species.
      Although no direct evidence has yet demonstrated the roles of these recent
      duplicated genes observed in E. grandis, this could indicate their putative
      implications in the morphological and physiological characteristics of E.
      grandis, and be the key factor for the survival of this nondormant species.
      Global analysis of key families would be a good criterion to evaluate the
      capabilities of some organisms to adapt to environmental variations. 

PMID- 25769697
TI  - National trends in the use of surgery for benign hepatic tumors in the United
      States.
AB  - BACKGROUND: The widespread use of diagnostic imaging has led to an increase in
      the incidence and diagnosis of benign liver tumors. The objective of this study
      was to define the overall use and temporal trends of operative procedures for
      benign liver tumors using a nationally representative cohort. METHODS: All
      patients who underwent liver surgery for benign liver tumors between 2000 and
      2011 were identified from the Nationwide Inpatient Sample database. Trends in
      annual volume of liver procedures were analyzed using the average annual percent
      change (AAPC) assessed by joinpoint analysis. RESULTS: There were 2,489 open
      (94.5%) and 144 (5.5%) minimally invasive surgical (MIS) procedures. Partial
      hepatectomy accounted for 43.8% of all cases (n = 1,153). Surgery for patients
      with benign liver tumors increased from 156 in 2000 to 272 in 2011 (AAPC, 5.8%;
      95% CI, 3.2-8.6%). There was decline in the relative use of open operative
      procedures from 98.1% in 2000 to 92.3% in 2011 (AAPC, -0.4%; 95% CI, -0.7 to 
      0.1%). In contrast, the proportion of MIS procedures increased from 1.9% in 2000
      to 7.7% in 2011 (AAPC, 7.4%; 95% CI, 1.9-13.3%). The median duration of stay
      among all patients was 5 days (interquartile range, 4-7; 5 days [open] vs 3 days
      [MIS]; P < .001). Inpatient mortality was 0.6% (n = 15 [open] vs n = 0 [MIS]; P =
      .43) and did not change during the study period (P > .05). CONCLUSION: Overall
      volume of surgical management of benign liver tumors has increased substantially
      over the past decade. There has been a relative shift away from open procedures
      toward MIS procedures.

PMID- 25769698
TI  - Bicuspid valve-related aortic disease: flow assessment with conventional phase
      contrast MRI.
AB  - RATIONALE AND OBJECTIVES: Abnormal blood flow with bicuspid aortic valve (BAV)
      has been characterized with four-dimensional flow magnetic resonance imaging
      (MRI), but this approach is time consuming and requires technical expertise. We
      assess the relationship between different leaflets fusion patterns with BAV,
      eccentric systolic flow, and dilation patterns of the ascending aorta using two
      dimensional (2D) phase-contrast (PC) MRI. MATERIALS AND METHODS: Fifty-nine
      patients with BAV who underwent cardiac MRI were identified; 47 had right-left
      (RL) aortic leaflet fusion and 12 had right-noncoronary (RN) fusion. Flow
      displacement was calculated, and patients with abnormal displacement (>0.1) were
      classified as either rightward or leftward. Patterns of aortopathy were
      determined (0-3), and correlation between leaflet fusion, flow direction,
      aortopathy type, and other clinical parameters was performed with Pearson
      correlation, the Fisher exact test and chi-square analysis. RESULTS: Normal
      systolic flow was seen in 24% of cases and was significantly correlated with
      normal aortas (P = .011). Abnormal flow displacement with RL fusion was strongly
      associated with rightward deviation (36 of 37 cases), whereas RN fusion skewed
      leftward (seven of eight cases; P < .01). In patients with aortopathy, RL fusion
      was strongly associated with type 2 aortopathy and RN with type 3 aortopathy (P <
      .01). CONCLUSIONS: Conventional PC MRI can identify abnormal systolic flow and
      differences in jet orientation with BAV. RL leaflet fusion is associated with
      rightward flow deviation and type 2 aortopathy, whereas RN fusion is linked to
      leftward deviation and type 3 aortopathy. The presence and direction of eccentric
      flow jets may help risk stratify these patients for valve-related aortic disease.

PMID- 25769699
TI  - [Driving-related dermatoses].

PMID- 25769701
TI  - Waugh syndrome in preterm infant: diagnostic clues.

PMID- 25769700
TI  - Treatment Results of Extracranial Malignant Germ Cell Tumor with Regimens of
      Cisplatin, Vinblastine, Bleomycin or Carboplatin, Etoposide, and Bleomycin with
      Special Emphasis on the Sites of Vagina and Testis.
AB  - BACKGROUND: The survival of children with malignant germ cell tumor (GCT)
      increased over the past 2 decades with platinum-based chemotherapy. This report
      has three objectives: (1) comparison of PVB (cisplatin, vinblastine, and
      bleomycin) with JEB (carboplatin, etoposide, and bleomycin) regimens; (2)
      treatment modality of vaginal GCT; and (3) management of stage I testicular yolk
      sac tumor (YST) in boys under 2 years old. METHODS: From January 1, 1987 to
      December 31, 2010, 81 patients with malignant extracranial GCT were treated. Two
      consecutive protocols, PVB followed by JEB, were used. Girls with vaginal YST
      received minimal surgery and chemotherapy. Boys under 2 years old with Stage I
      testicular YST received surgery with or without chemotherapy. RESULTS: As of June
      30, 2012, the 10-year overall survival (OS) was 95 +/- 3% (standard error) and
      the event-free survival (EFS) was 88 +/- 4%. With PVB, 35 patients had 10-year OS
      of 91 +/- 5% and EFS of 89 +/- 5%. With JEB, 25 patients had 7-year OS of 96 +/-
      5% and EFS of 96 +/- 5%. All five girls with vaginal YST were cured with vagina
      preserved strategy. In 32 boys age under 2 years old with stage I YST, 16 with
      light chemotherapy were all in EFS, whereas two of 16 patients without
      chemotherapy relapsed. After PVB, six patients developed nephrotoxicity and one
      had pulmonary fibrosis. CONCLUSION: Girls with vaginal YST who received minimal
      surgery and chemotherapy had excellent prognosis and sexual organs were
      preservable. Light chemotherapy after surgery is a treatment option for boys
      under 2 years old with stage I YST to decrease relapse rate. Both JEB and PVB are
      effective. JEB resulted in more myelosuppression but otherwise less serious long
      term toxicity than PVB.

PMID- 25769702
TI  - Behavior management: key regulatory issues.

PMID- 25769703
TI  - Feasibility of a web-based dementia feeding skills training program for nursing
      home staff.
AB  - Nursing home (NH) staff do not receive adequate training for providing feeding
      assistance to residents with dementia who exhibit aversive feeding behaviors
      (e.g., clamping mouth shut). The result is often low meal intake for these
      residents. This feasibility study tested a web-based dementia feeding skills
      program for staff in two United States NHs. Randomly assigned, the intervention
      staff received web-based dementia feeding skills training with coaching. Both
      groups participated in web-based pre-/post-tests assessing staff knowledge and
      self-efficacy; and meal observations measured NH staff and resident feeding
      behaviors, time for meal assistance, and meal intake. Aversive feeding behaviors
      increased in both groups of residents; however, the intervention NH staff
      increased the amount of time spent providing assistance and meal intake doubled.
      In the control group, less time was spent providing assistance and meal intake
      decreased. This study suggests that training staff to use current clinical
      practice guidelines improves meal intake. 

PMID- 25769704
TI  - Role of tumor-associated glycoprotein-72 in the progression of endometrial
      adenocarcinoma: a proposed study.
AB  - Endometrial adenocarcinoma is on the basis of the molecular, immunohistological
      and clinicopathologic features broadly divided into two groups, referred as type
      I and type II. Type I appears more frequently and in principle patients have a
      good prognosis; however a significant number of patients develop local
      recurrences. We hypothesize that TAG-72, expressed on endometrial carcinoma binds
      and internalizes endocytic pattern recognition receptors on surrounding tissue
      antigen presenting cells (dendritic cells and macrophages), powers their anti
      inflammatory maturation program and make them capable to elicit or modulated
      tolerogenic immune response mediated by local T and NK effectors. This could
      support uncontrolled local tumor growth, deeper tumor invasion into surrounding
      tissues, frequent local recurrences and/or lymph node metastasis. To test this
      hypothesis, we propose a semi-quantitative immunohistochemical analysis of TAG-72
      expression in endometrial adenocarcinoma samples and to correlate the results
      with clinical and pathological parameters (age, type and histological grade of
      the tumor, estrogen and progesterone receptor expression, invasion into the
      myometrium and capillaries, presence of lymph node metastases, FIGO stage, and
      TNM classification). It would be worthwhile to investigate the local tissue
      immune response in the tumor environment using tissue samples removed during
      surgery. These studies could elucidate the underlying immunopathological
      mechanisms that govern the early recurrence and possibly distant metastases of
      TAG-72-expressing adenocarcinomas and might help in deciding the type of
      treatment to be applied in a selected group of cancer patients including
      application of biological therapy with anti-TAG-72 antibodies, according the
      principle of personalized oncology treatments. 

PMID- 25769705
TI  - On the existence of cardiomesenchymal stem cells.
AB  - The most efficient cells for cardiac regeneration are myocardium-resident cardiac
      stem cells. However, the limited availability of these cells restricts their
      utility for cardiac cellular therapy. Mesenchymal stem cells can differentiate
      into a wide variety of tissues, but it is not simple to accurately direct cell
      differentiation into a specific lineage, such as cardiac tissue; this renders a
      low efficiency for cardiac regeneration therapy. Given the heterogeneity of
      mesenchymal stem cells, it may be possible to find specific stem cell
      subpopulations with a definite differentiation capacity toward cardiac lineage. A
      parameter to assess cardiac differentiation specificity could be surface marker
      expression; a population with an immunophenotype similar to cardiac stem cells
      may have a superior therapeutic value than unsorted mesenchymal stem cells. We
      hypothesize the existence of a cell line that combines the expression of cardiac
      stem cell surface markers with those of mesenchymal stem cells, a suitable name
      for this population is cardiomesenchymal stem cells (CMSC); such cells would be
      ideal for cardiac regeneration. 

PMID- 25769706
TI  - Does lysozyme play a role in the pathogenesis of COPD?
AB  - Elastic fiber injury is an important process in the pathogenesis of chronic
      obstructive pulmonary disease (COPD), particularly with regard to the development
      of pulmonary emphysema. Damage to these fibers results in uneven distribution of
      mechanical forces in the lung, leading to dilatation and rupture of alveolar
      walls. While the role of various enzymes and oxidants in this process has been
      well-documented, we propose that a previously unsuspected agent, lysozyme, may
      contribute significantly to the changes in elastic fibers observed in this
      disease. Studies from our laboratory have previously shown that lysozyme
      preferentially binds to elastic fibers in human emphysematous lungs. On the basis
      of this finding, it is hypothesized that the attachment of lysozyme to these
      fibers enhances their susceptibility to injury, and further impairs the transfer
      of mechanical forces in the lung, leading to increased alveolar wall damage and
      enhanced progression of COPD. The hypothesized effects of lysozyme are predicated
      on its interaction with hyaluronan (HA), a long-chain polysaccharide that is
      found in close proximity to elastic fibers. By preventing the binding of HA to
      elastic fibers in COPD, lysozyme may interfere with the protective effect of this
      polysaccharide against enzymes and oxidants that degrade these fibers.
      Furthermore, the loss of the hydrating effect of HA on these fibers may impair
      their elastic properties, greatly increasing the probability of their
      fragmentation in response to mechanical forces. The proposed hypothesis may
      explain why the content of HA is significantly lower in the lungs of COPD
      patients. It may also contribute to the design of clinical trials involving the
      use of exogenously administered HA as a potential treatment for COPD. 

PMID- 25769707
TI  - Current staging and prognostic factors in melanoma.
AB  - The current American Joint Commission for Cancer staging system for melanoma
      includes thickness, ulceration, and mitotic index as primary tumor factors for
      patients with stage I and II disease. Number and size of nodal metastases,
      presence of satellitosis and in-transit disease, and tumor ulceration status
      categorize patients with stage III disease. Presence and location of distant
      metastatic disease and increased lactate dehydrogenase level stratify prognosis
      in patients with stage IV disease. Factors predictive of sentinel lymph node
      positivity are also studied, particularly in patients with T1 melanomas, but are
      not always congruent with those predictive of survival. 

PMID- 25769708
TI  - Pathology of melanoma.
AB  - The pathology of melanoma is discussed in relation to surgical diagnosis and
      management. Pitfalls that may result in problems of clinicopathologic
      communication are emphasized. A compelling vision for the future is that all
      tumors will be characterized by their driving oncogenes, suppressor genes, and
      other genomic factors. The success of targeted therapy directed against
      individual oncogenes, despite its limitations, suggests that a repertoire of
      targeted agents will be developed that can be used against a variety of different
      tumors, depending on the results of genetic testing. Nevertheless,
      histopathologic diagnosis and surgical therapy will remain mainstays of
      management for melanoma.

PMID- 25769709
TI  - Surgical management of primary and recurrent melanoma.
AB  - Melanoma accounts for less than 2% of skin cancer cases but causes most skin
      cancer-related deaths. Surgery continues to be the cornerstone of treatment of
      melanoma and surgical principles are guided by data derived from clinical
      research. This article examines the evolution of surgical techniques for the
      diagnosis and treatment of primary and locally recurrent melanoma. 

PMID- 25769710
TI  - Sentinel lymph node mapping in melanoma in the twenty-first century.
AB  - The incidence of melanoma is increasing faster than any other cancer. The status
      of the regional nodal basin remains the most important prognostic factor.
      Sentinel lymph node biopsy (SLNB) is recommended for staging in patients
      diagnosed with intermediate-thickness melanoma (1.01-4.0 mm). SLNB is considered
      somewhat controversial, especially when used to stage thin (1 mm), thick (>4 mm),
      or desmoplastic melanoma. This article reviews the current literature regarding
      SLNB in thin, intermediate, thick, and desmoplastic melanoma. Data supporting the
      use of newer radiopharmaceuticals in sentinel lymph node mapping along with newer
      imaging modalities are also reviewed.

PMID- 25769711
TI  - Lymph node dissection for stage III melanoma.
AB  - Locoregional spread of melanoma to its draining lymph node basin is the strongest
      negative prognostic factor for patients. Exclusive of clinical trials, patients
      with sentinel lymph node-positive (microscopic) or clinically palpable
      (macroscopic) nodal disease should undergo lymphadenectomy. This article reviews
      the management and technical aspects of surgical care for regional metastases.
      Adjunct therapies (immunotherapy, targeted therapy, and radiation) may supplement
      lymphadenectomy in certain patient populations. Surgical morbidity after
      lymphadenectomy can be substantial, creating opportunities for improvement via
      minimally invasive techniques or refined patient selection. 

PMID- 25769712
TI  - Metastasectomy for stage IV melanoma.
AB  - Metastatic melanoma has an unpredictable natural history but a predictably high
      mortality. Despite recent advances in systemic therapy, many patients do not
      respond, or develop resistance to drug therapy. Surgery has consistently shown
      good outcomes in appropriately selected patients. It is likely to be even more
      successful in the era of more effective medical treatment. Surgery should remain
      a strongly considered option for metastatic melanoma. 

PMID- 25769713
TI  - Intralesional therapy for in-transit and satellite metastases in melanoma.
AB  - Intratumoral therapy with bacteria/bacterial products dates to at least the
      1890s. Over the decades this has expanded beyond the use of microbes and
      microbial products to include chemicals, cancer chemotherapeutic agents,
      cytokines, recombinant organisms, and hybrid molecules. The appeal of this method
      of delivery is the ability to deliver high concentrations of the therapeutic
      agent directly to the tumor, often with minimal side effects. This article
      summarizes the use and efficacy of the various agents used in the past and
      present in the treatment of in-transit and satellite metastases in melanoma.

PMID- 25769715
TI  - Role for radiation therapy in melanoma.
AB  - Although melanoma is generally considered a relative radioresistant tumor,
      radiation therapy (RT) remains a valid and effective treatment option in
      definitive, adjuvant, and palliative settings. Definitive RT is generally only
      used in inoperable patients. Despite a high-quality clinical trial showing
      adjuvant RT following lymphadenectomy in node-positive melanoma patients prevents
      local and regional recurrence, the role of adjuvant RT in the treatment of
      melanoma remains controversial and is underused. RT is highly effective in
      providing symptom palliation for metastatic melanoma. RT combined with new
      systemic options, such as immunotherapy, holds promise and is being actively
      evaluated. 

PMID- 25769714
TI  - Regional therapies for in-transit disease.
AB  - In-transit melanoma is an uncommon pattern of recurrence, but presents unique
      management challenges and opportunities for treatment. The clinical presentation
      usually involves from 1 to more than 100 small subcutaneous or cutaneous nodules,
      ranging from submillimeter to multiple centimeters in diameter. Regional
      chemotherapy techniques are a mainstay of treatment of patients without systemic
      disease spread. Future applications of regional therapy are likely to involve
      combination therapy with cytotoxic agents and novel immune modulators. Regional
      therapy provides distinct opportunities for the treatment of unresectable
      disease, and offers a unique platform for investigation of novel therapeutics in
      early-stage clinical trials. 

PMID- 25769716
TI  - Update on immunotherapy in melanoma.
AB  - Immunotherapy is now recognized as a viable option for patients with metastatic
      melanoma. The field of immunotherapy now offers treatments with the potential for
      a long-term cure. As the field moves forward, studies will focus on improving the
      response rates with new immunotherapy agents or novel treatment combinations. 

PMID- 25769717
TI  - Targeted therapies in melanoma.
AB  - Advances in the biology of melanoma have provided insights about chemoresistance
      and its genetic heterogeneity in parallel with advances in drug design,
      culminating in recent major treatment breakthroughs. Although clinical benefit of
      targeted therapies has been unquestionable, future advances are only possible if
      we understand the interplay between genetic aberrations and role of other crucial
      nongenetic changes yet to be identified by such projects as the Cancer Genome
      Atlas Project in Melanoma. Combination therapies, either among small molecule
      inhibitors themselves and/or with immunotherapies, may be the optimal strategy to
      prevent development of drug resistance inherently linked with such targeted
      therapies. 

PMID- 25769719
TI  - Melanoma.

PMID- 25769718
TI  - Long-term follow-up for melanoma patients: is there any evidence of a benefit?
AB  - As the incidence of melanoma and the number of melanoma survivors continues to
      rise, optimal surveillance strategies are needed that balance the risks and
      benefits of screening in the context of contemporary resource use. Detection of
      recurrences has important implications for clinical management. Most current
      surveillance recommendations for melanoma survivors are based on low-level
      evidence with wide variations in practice patterns and an unknown clinical impact
      for the melanoma survivor. 

PMID- 25769720
TI  - Melanoma.

PMID- 25769721
TI  - miR-21 Inhibition Reduces Liver Fibrosis and Prevents Tumor Development by
      Inducing Apoptosis of CD24+ Progenitor Cells.
AB  - miR-21 is upregulated in hepatocellular carcinoma and intrahepatic
      cholangiocarcinoma, where it is associated with poor prognosis. Here, we offer
      preclinical evidence that miR-21 offers a therapeutic and chemopreventive target
      in these liver cancers. In mice with hepatic deletion of Pten, anti-miR-21
      treatment reduced liver tumor growth and prevented tumor development. These
      effects were accompanied with a decrease in liver fibrosis and a concomitant
      reduction of CD24(+) liver progenitor cells and S100A4(+) cancer-associated
      stromal cells. Notch2 inhibition also occurred in tumors following anti-miR-21
      treatment. We further showed that miR-21 is necessary for the survival of CD24(+)
      progenitor cells, a cellular phenotype mediated by Notch2, osteopontin, and
      integrin alphav. Our results identify miR-21 as a key regulator of tumor
      initiating cell survival, malignant development, and growth in liver cancer,
      highlighting the role of CD24(+) cells in the expansion of S100A4(+) cancer
      associated stromal cells and associated liver fibrosis.

PMID- 25769722
TI  - Paracrine WNT5A Signaling Inhibits Expansion of Tumor-Initiating Cells.
AB  - It is not well understood how paracrine communication between basal and luminal
      cell populations in the mammary gland affects tumorigenesis. During ErbB2-induced
      mammary tumorigenesis, enriched mammary stem cells that represent a subpopulation
      of basal cells exhibit enhanced tumorigenic capacity compared with the
      corresponding luminal progenitors. Transcript profiling of tumors derived from
      basal and luminal tumor-initiating cells (TIC) revealed preferential loss of the
      noncanonical Wnt ligand WNT5A in basal TIC-derived tumors. Heterozygous loss of
      WNT5A was correlated with shorter survival of breast cancer patients. In a mouse
      model of ErbB2-induced breast cancer, Wnt5a heterozygosity promoted tumor
      multiplicity and pulmonary metastasis. As a TGFbeta substrate, luminal cell
      produced WNT5A induced a feed-forward loop to activate SMAD2 in a RYK and
      TGFbetaR1-dependent manner to limit the expansion of basal TIC in a paracrine
      fashion, a potential explanation for the suppressive effect of WNT5A in mammary
      tumorigenesis. Our results identify the WNT5A/RYK module as a spatial regulator
      of the TGFbeta-SMAD signaling pathway in the context of mammary gland development
      and carcinogenesis, offering a new perspective on tumor suppression provided by
      basal-luminal cross-talk in normal mammary tissue.

PMID- 25769725
TI  - Histone Deacetylase Inhibitors Repress Tumoral Expression of the Proinvasive
      Factor RUNX2.
AB  - Aberrant reactivation of embryonic pathways occurs commonly in cancer. The
      transcription factor RUNX2 plays a fundamental role during embryogenesis and is
      aberrantly reactivated during progression and metastasization of different types
      of human tumors. In this study, we attempted to dissect the molecular mechanisms
      governing RUNX2 expression and its aberrant reactivation. We identified a new
      regulatory enhancer element, located within the RUNX2 gene, which is responsible
      for the activation of the RUNX2 promoter and for the regulation of its expression
      in cancer cells. Furthermore, we have shown that treatment with the anticancer
      compounds histone deacetylase inhibitor (HDACi) results in a profound inhibition
      of RUNX2 expression, which is determined by the disruption of the transcription
      activating complex on the identified enhancer. These data envisage a possible
      targeting strategy to counteract the oncongenic function of RUNX2 in cancer cells
      and provide evidence that the cytotoxic activity of HDACi in cancer is not only
      dependent on the reactivation of silenced oncosuppressors but also on the
      repression of oncogenic factors that are necessary for survival and progression.

PMID- 25769723
TI  - The endogenous cell-fate factor dachshund restrains prostate epithelial cell
      migration via repression of cytokine secretion via a cxcl signaling module.
AB  - Prostate cancer is the second leading form of cancer-related death in men. In a
      subset of prostate cancer patients, increased chemokine signaling IL8 and IL6
      correlates with castrate-resistant prostate cancer (CRPC). IL8 and IL6 are
      produced by prostate epithelial cells and promote prostate cancer cell invasion;
      however, the mechanisms restraining prostate epithelial cell cytokine secretion
      are poorly understood. Herein, the cell-fate determinant factor DACH1 inhibited
      CRPC tumor growth in mice. Using Dach1(fl/fl)/Probasin-Cre bitransgenic mice, we
      show IL8 and IL6 secretion was altered by approximately 1,000-fold by endogenous
      Dach1. Endogenous Dach1 is shown to serve as a key endogenous restraint to
      prostate epithelial cell growth and restrains migration via CXCL signaling. DACH1
      inhibited expression, transcription, and secretion of the CXCL genes (IL8 and
      IL6) by binding to their promoter regulatory regions in chromatin. DACH1 is thus
      a newly defined determinant of benign and malignant prostate epithelium cellular
      growth, migration, and cytokine abundance in vivo.

PMID- 25769724
TI  - Metabolic signature identifies novel targets for drug resistance in multiple
      myeloma.
AB  - Drug resistance remains a major clinical challenge for cancer treatment. Multiple
      myeloma is an incurable plasma cell cancer selectively localized in the bone
      marrow. The main cause of resistance in myeloma is the minimal residual disease
      cells that are resistant to the original therapy, including bortezomib treatment
      and high-dose melphalan in stem cell transplant. In this study, we demonstrate
      that altered tumor cell metabolism is essential for the regulation of drug
      resistance in multiple myeloma cells. We show the unprecedented role of the
      metabolic phenotype in inducing drug resistance through LDHA and HIF1A in
      multiple myeloma, and that specific inhibition of LDHA and HIF1A can restore
      sensitivity to therapeutic agents such as bortezomib and can also inhibit tumor
      growth induced by altered metabolism. Knockdown of LDHA can restore sensitivity
      of bortezomib resistance cell lines while gain-of-function studies using LDHA or
      HIF1A induced resistance in bortezomib-sensitive cell lines. Taken together,
      these data suggest that HIF1A and LDHA are important targets for hypoxia-driven
      drug resistance. Novel drugs that regulate metabolic pathways in multiple
      myeloma, specifically targeting LDHA, can be beneficial to inhibit tumor growth
      and overcome drug resistance.

PMID- 25769727
TI  - RSPO2 Enhances Canonical Wnt Signaling to Confer Stemness-Associated Traits to
      Susceptible Pancreatic Cancer Cells.
AB  - Cancer stem cells (CSC) present a formidable clinical challenge by escaping
      therapeutic intervention and seeding tumors through processes that remain
      incompletely understood. Here, we describe small subpopulations of pancreatic
      cancer cells with high intrinsic Wnt activity (Wnt(high)) that possess properties
      indicative of CSCs, including drug resistance and tumor-initiating capacity,
      whereas cell populations with negligible Wnt activity (Wnt(low)) preferentially
      express markers of differentiation. Spontaneous response to extrinsic Wnt signals
      induces signaling networks comprising ERK1/2 and epithelial-mesenchymal
      transition that subsequently confer cancer stemness traits to susceptible cells.
      Wnt enhancer R-Spondin 2 (RSPO2) seems to play a prominent upstream role in
      regulating this interplay. In this context, Wnt(high) cells were more likely to
      give rise to Wnt(high) progeny, tended to be more metastatic, and revealed higher
      levels of RSPO2 expression. Our studies reveal adaptive aspects of pancreatic
      cancer stemness arising from driver populations of CSCs that misappropriate
      functional and responsive elements of archetypical self-renewal pathways.
      Blocking such stemness-promoting pathways in conjunction with established
      chemotherapy could provide means to disrupt dynamic CSC process and present novel
      therapeutic targets and strategies.

PMID- 25769726
TI  - Induction of Vasculogenic Mimicry Overrides VEGF-A Silencing and Enriches Stem
      like Cancer Cells in Melanoma.
AB  - The basis for resistance to VEGF inhibition is not fully understood despite its
      clinical importance. In this study, we examined the adaptive response to VEGF-A
      inhibition by a loss-of-function analysis using plasmid-based shRNA. Tumor
      xenografts that initially responded to VEGF-A inhibition underwent an adaptation
      in vivo, leading to acquired resistance. VEGF-A blockade in tumors was associated
      with HIF1alpha expression and an increase in CD144(+) vasculogenic mimicry (VM),
      leading to formation of channels displaying Tie-1 and MMP-2 upregulation.
      CD133(+) and CD271(+) melanoma stem-like cells (MSLC) accumulated in the
      perivascular niche. Tumor xenografts of melanoma cell populations that were
      intrinsically resistant to VEGF-A blockade did not exhibit any of these features,
      compared with nontarget control counterparts. Thus, melanomas that are initially
      sensitive to VEGF-A blockade acquire adaptive resistance by adopting VM as an
      alternate angiogenic strategy, thereby enriching for deposition of MSLC in the
      perivascular niche through an HIF1alpha-dependent process. Conversely, melanomas
      that are intrinsically resistant to VEGF-A blockade do not show any evidence of
      compensatory survival mechanisms that promote MSLC accumulation. Our work
      highlights the potential risk of anti-VEGF treatments owing to a selective
      pressure for an adaptive resistance mechanism that empowers the development of
      stem-like cancer cells, with implications for how to design combination therapies
      that can improve outcomes in patients.

PMID- 25769728
TI  - Putting my money where my mouth is: the Useful Genetics project.
AB  - The personal and societal importance of genetics has increased dramatically since
      the 1950s, but most introductory courses still focus on teaching students how to
      think like geneticists, training them in Mendelian and molecular analysis. This
      article is a personal account of a new course with a different goal, giving
      students knowledge and skills that they can use in their nonacademic lives.
      Useful Genetics differs from typical courses in emphasizing personal genomics,
      natural genetic and phenotypic variation in humans, and the consequences of
      genetic inheritance for breeding, inbreeding, and ancestry. Although it is a
      Massive Open Online Course (MOOC), taught to large global populations of learners
      of all ages and backgrounds, it maintains the academic rigor of a college course.
      The course materials are freely available for reuse by other instructors, and are
      being used as the foundation of a face-to-face university credit course. 

PMID- 25769729
TI  - Supporting nursing student supervision: An assessment of an innovative approach
      to supervisor support.
AB  - The responsibility for clinical supervision is recognised by both the nursing
      literature and the Australian Nursing and Midwifery Council, through an
      expectation that RNs will provide support and facilitate student learning in the
      clinical environment (Atack et al., 2000; Gray and Smith, 2000; Brammer, 2005;
      Australian Nursing and Midwifery Council, 2006; Hallin and Danielson, 2008). RNs
      identify with and acknowledge the need for the supervisory role and are willing
      participants however, request strategies to guide and support students in the
      clinical environment (Bourbonnais and Kerr, 2007; Hallin and Danielson, 2008).
      OBJECTIVES: The aim of this study was to provide a means of support to clinical
      supervisors of nursing students through a computer-based clinical supervisor
      educational package (CSEP) and to test the effectiveness of the CSEP. DESIGN: The
      effectiveness of the CSEP was determined by a pre-test-post-test evaluation sheet
      that included open and Likert scale questions. SETTINGS: 4 regional hospitals in
      South Australia, Australia. PARTICIPANTS: 28 participants completed the
      questionnaire on their experience with the CSEP. METHODS: Analysis of
      quantitative data utilised non-parametric testing with SPSS version 20. A
      Wilcoxon Signed Rank Test was performed on the Likert scale questions to
      establish any significant difference between the pre- and post-tests. The
      responses to the open-ended questions were thematically analysed separately by
      the two authors. The themes were then amalgamated. The results were then compared
      to find similarities or differences. CONCLUSIONS: The CSEP is an effective
      education package in promoting increased preparedness to supervise and increased
      confidence to promote learning.

PMID- 25769730
TI  - Kinematic analysis of video-captured falls experienced by older adults in long
      term care.
AB  - Falls cause 95% of hip and wrist fractures and 60% of head injuries in older
      adults. Risk for such injuries depends in part on velocity at contact, and the
      time available during the fall to generate protective responses. However, we have
      no information on the impact velocities and durations of falls in older adults.
      We addressed this barrier through kinematic analysis of 25 real-life falls
      (experienced by 23 individuals of mean age 80 years (SD=9.8)) captured on video
      in two long-term facilities. All 25 falls involved impact to the pelvis, 12
      involved head impact, and 21 involved hand impact. We determined time-varying
      positions by digitizing each video, using direct linear transformations
      calibrated for each fall, and impact velocities through differentiation. The
      vertical impact velocity averaged 2.14 m/s (SD=0.63) for the pelvis, 2.91 m/s
      (SD=0.86) for the head, and 2.87 m/s (SD=1.60) for the hand. These values are
      38%, 28%, and 4% lower, respectively, than predictions from an inverted pendulum
      model. Furthermore, the average pelvis impact velocity was 16% lower than values
      reported previously for young individuals in laboratory falling experiments. The
      average fall duration was 1271 ms (SD=648) from the initiation of imbalance to
      pelvis impact, and 583 ms (SD=255) from the start of descent to pelvis impact.
      These first measures of the kinematics of falls in older adults can inform the
      design and testing of fall injury prevention interventions (e.g., hip protectors,
      helmets, and flooring).

PMID- 25769731
TI  - Analysis and analytical characterization of bioheat transfer during
      radiofrequency ablation.
AB  - Understanding thermal transport and temperature distribution within biological
      organs is important for therapeutic aspects related to hyperthermia treatments
      such as radiofrequency ablation (RFA). Unlike surface heating, the RFA treatment
      volumetrically heats up the biological media using a heating probe which provides
      the input energy. In this situation, the shape of the affected region is annular,
      which is described by an axisymmetric geometry. To better understand the
      temperature responses of the living tissues subject to RFA, comprehensive
      characteristics of bioheat transport through the annular biological medium is
      presented under local thermal non-equilibrium (LTNE) condition. Following the
      operational features of the RFA treatment, based on the porous media theory,
      analytical solutions have been derived for the blood and tissue temperature
      distributions as well as an overall heat exchange correlation in cylindrical
      coordinates. Our analytical results have been validated against three limiting
      cases which exist in the literature. The effects of various physiological
      parameters, such as metabolic heat generation, volume fraction of the vascular
      space, ratio of the effective blood to tissue conductivities, different
      biological media and the rate of heat exchange between the lumen and the tissue
      are investigated. Solutions developed in this study are valuable for thermal
      therapy planning of RFA. A criterion is also established to link deep heating
      protocol to surface heating. 

PMID- 25769732
TI  - Aging- and task-related resilience decline is linked to food responsiveness in
      highly social honey bees.
AB  - Conventional invertebrate models of aging have provided striking examples for the
      influence of food- and nutrient-sensing on lifespan and stress resilience. On the
      other hand, studies in highly social insects, such as honey bees, have revealed
      how social context can shape very plastic life-history traits, for example
      flexible aging dynamics in the helper caste (workers). It is, however, not
      understood how food perception and stress resilience are connected in honey bee
      workers with different social task behaviors and aging dynamics. To explore this
      linkage, we tested if starvation resilience, which normally declines with age,
      depends on food responsiveness in honey bees. We studied two typically non
      senesced groups of worker bees with different social task behaviors: mature
      nurses (caregivers) and mature foragers (food collectors). In addition, we
      included a group of old foragers for which functional senescence is well
      established. Bees were individually scored for their food perception by measuring
      the gustatory response to different sucrose concentrations. Subsequently,
      individuals were tested for survival under starvation stress. We found that
      starvation stress resilience, but not gustatory responsiveness differed between
      workers with different social task behaviors (mature nurses vs. mature foragers).
      In addition starvation stress resilience differed between foragers with different
      aging progressions (mature foragers vs. old foragers). Control experiments
      confirmed that differences in starvation resilience between mature nurses and
      mature foragers were robust against changing experimental conditions, such as
      water provision and activity. For all worker groups we established that
      individuals with low gustatory responsiveness were more resilient to starvation
      stress. Finally, for the group of rapidly aging foragers we found that low food
      responsiveness was linked to a delayed age-related decline in starvation
      resilience. Our study highlights associations between reduced food perception,
      increased survival capacity and delayed aging in highly social honey bees. We
      discuss that these associations may involve canonical internal nutrient sensing
      pathways, which are shared between honey bees and animal models with less plastic
      aging dynamics. 

PMID- 25769733
TI  - Reasons for longer hospital waiting times need to be understood, says Nuffield
      Trust.

PMID- 25769735
TI  - AD8 Informant Questionnaire for Cognitive Impairment: Pragmatic Diagnostic Test
      Accuracy Study.
AB  - The diagnostic accuracy of the AD8 informant questionnaire for cognitive
      impairment was assessed in patients referred to a dedicated memory clinic. This
      pragmatic prospective study of consecutive referrals attending with an informant
      who completed AD8 (n = 212) lasted 12 months. Diagnosis used standard clinical
      diagnostic criteria for dementia and mild cognitive impairment as reference
      standard (prevalence of cognitive impairment = 0.62). The AD8 proved acceptable
      to informants, was quick, and easy to use. Using the cutoff of >=2/8, AD8 was
      highly sensitive (0.97) for diagnosis of cognitive impairment but specificity was
      poor (0.17). Combining AD8 with either the Mini-Mental State Examination or the
      Six-Item Cognitive Impairment Test showed little additional diagnostic benefit.
      In conclusion, AD8 is very sensitive for cognitive impairment in a memory clinic
      but specificity may be inadequate. 

PMID- 25769736
TI  - Evaluation of late presentation for HIV treatment in a reference center in Belo
      Horizonte, Southeastern Brazil, from 2008 to 2010.
AB  - INTRODUCTION: Since 1996 Brazil has provided universal access to free
      antiretroviral therapy, and as a consequence, HIV/AIDS patients' survival rate
      has improved dramatically. However, according to scientific reports, a
      significant number of patients are still late presenting for HIV treatment, which
      leads to consequences both for the individual and society. Clinical and
      immunological characteristics of HIV patients newly diagnosed were accessed and
      factors associated with late presentation for treatment were evaluated. METHODS:
      A cross-sectional study was carried out in an HIV/AIDS reference center in Belo
      Horizonte, Minas Gerais, in Southeastern Brazil from 2008 to 2010. Operationally,
      patients with late presentation (LP) for treatment were those whose first CD4
      cell count was less than 350 cells/mm(3) or presented an AIDS defining
      opportunistic infection. Patients with late presentation with advanced disease
      (LPAD) were those whose first CD4 cell count was less than 200 cells/mm(3) or
      presented an AIDS defining opportunistic infection. LP and LPAD associated risk
      factors were evaluated using logistic regression methods. RESULTS: Five hundred
      and twenty patients were included in the analysis. The median CD4 cell count was
      336 cells/mm(3) (IQR: 130-531). Two hundred and seventy-nine patients (53.7%)
      were classified as LP and 193 (37.1%) as LPAD. On average, 75% of the patients
      presented with a viral load (VL) >10,000 copies/ml. In multivariate logistic
      regression analysis the factors associated with LP and LPAD were age, being
      symptomatic at first visit and VL. Race was a factor associated with LP but not
      with LPAD. CONCLUSION: The proportion of patients who were late attending a
      clinic for HIV treatment is still high, and effective strategies to improve early
      HIV detection with a special focus on the vulnerable population are urgently
      needed.

PMID- 25769734
TI  - Evolution and function of the TCR Vgamma9 chain repertoire: It's good to be
      public.
AB  - Lymphocytes expressing a T cell receptor (TCR) composed of Vgamma9 and Vdelta2
      chains represent a minor fraction of human thymocytes. Extrathymic selection
      throughout post-natal life causes the proportion of cells with a Vgamma9-JP
      rearrangement to increase and elevates the capacity for responding to non
      peptidic phosphoantigens. Extrathymic selection is so powerful that
      phosphoantigen-reactive cells comprise about 1 in 40 circulating memory T cells
      in healthy adults and the subset expands rapidly upon infection or in response to
      malignancy. Skewing of the gamma delta TCR repertoire is accompanied by selection
      for public gamma chain sequences such that many unrelated individuals overlap
      extensive in their circulating repertoire. This type of selection implies the
      presence of a monomorphic antigen-presenting molecule that is an object of
      current research but remains incompletely defined. While selection on a
      monomorphic presenting molecule may seem unusual, similar mechanisms shape the
      alpha beta T cell repertoire including the extreme examples of NKT or mucosal
      associated invariant T cells (MAIT) and the less dramatic amplification of public
      Vbeta chain rearrangements driven by individual MHC molecules and associated with
      resistance to viral pathogens. Selecting and amplifying public T cell receptors
      whether alpha beta or gamma delta, are important steps in developing an
      anticipatory TCR repertoire. Cell clones expressing public TCR can accelerate the
      kinetics of response to pathogens and impact host survival. 

PMID- 25769738
TI  - Who wants to adopt and who wants to be adopted: a sample of American families and
      sub-Saharan African orphans.
AB  - The debate between pro- and anti-international adoption advocates relies heavily
      on rhetoric and little on data analysis. To better understand the state of
      orphans and potential adopters in this debate, we utilize the National Survey of
      Family Growth (NSFG) and the Demographic and Health Surveys (DHS) to study who
      adopts internationally and the status of orphaned children in sub-Saharan Africa.
      According to NSFG data adopters are church going, highly educated, stable
      families aware of the challenges faced by international adoption, with high rates
      of infertility and rates of child abuse half the population average. According to
      the DHS data, orphans in sub-Saharan Africa suffer from significantly higher
      deprivation, reduced schooling and increased levels of stunting and underweight
      reported than their cohort. Using this data, we estimate conservatively that that
      1 50 000 orphans from our sample of sub-Saharan African countries died from their
      5-year birth cohort. Given the large number of families seeking to adopt and the
      high number of orphan deaths, it seems counterproductive to restrict
      international adoptions given the significantly lower risks faced by children in
      adopted families compared with remaining orphaned. 

PMID- 25769737
TI  - Prevalence of hepatitis B and C virus infections among military personnel.
AB  - BACKGROUND: Data regarding Hepatitis B and C viruses (HBV and HCV) prevalence
      among military personnel in Brazil are lacking, but the work-related risk of
      exposure can be high. The objective of this study was to estimate the
      seroprevalence of HBV and HCV and the risk factors associated to HBV exposure
      among Brazilian military personnel. METHODS: A cross-sectional study was
      conducted and included 433 male military adults aged 18-25 years old working in
      Rio de Janeiro during October 2013. All individuals completed a questionnaire to
      assess their risk of exposure and provided a blood sample to HBV and HCV testing.
      RESULTS: None of the participants presented HBsAg or anti-HBc IgM, 18 (4.1%) were
      positive for total anti-HBc, 247 (57.0%) were positive for anti-HBs, and 3 (0.7%)
      were anti-HCV reactive. The majority of military personnel with past HBV
      infection (anti-HBc reactive) and HBV immunity (anti-HBs reactive) had a history
      of prior dental procedures (88.9% and 77.3%), consumption of alcohol at least
      once a week (50% and 55.9%), and practiced oral sex (61.1% and 58.3%,
      respectively). In addition, anti-HBc positivity was common among individuals with
      a history of surgery (44.4%) and practice of anal sex (50%). At univariate
      analysis, age group was associated to anti-HBc and anti-HBs positivity.
      CONCLUSIONS: Low rates of HBV and HCV infection were observed among Brazilian
      military personnel in comparison to the general Brazilian population. HBV
      immunity rates were relatively low indicating the need for vaccination campaigns
      in this group.

PMID- 25769739
TI  - Use of health care among febrile children from urban poor households in Senegal:
      does the neighbourhood have an impact?
AB  - Urban malaria is considered a major public health problem in Africa. The malaria
      vector is well adapted in urban settings and autochthonous malaria has increased.
      Antimalarial treatments prescribed presumptively or after rapid diagnostic tests
      are also highly used in urban settings. Furthermore, health care strategies for
      urban malaria must comply with heterogeneous neighbourhood ecosystems where
      health-related risks and opportunities are spatially varied. This article aims to
      assess the capacity of the urban living environment to mitigate or increase
      individual or household vulnerabilities that influence the use of health
      services. The data are drawn from a survey on urban malaria conducted between
      2008 and 2009. The study sample was selected using a two-stage randomized
      sampling. The questionnaire survey covered 2952 households that reported a case
      of fever episode in children below 10 years during the month before the
      survey.Self-medication is a widespread practice for children, particularly among
      the poorest households in Dakar. For rich households, self-medication for
      children is more a transitional practice enabling families to avoid opportunity
      costs related to visits to health facilities. For the poorest, it is a forced
      choice and often the only treatment option. However, the poor that live in well
      equipped neighbourhoods inhabited by wealthy residents tend to behave as their
      rich neighbours. They grasp the opportunities provided by the area and adjust
      their behaviours accordingly. Though health care for children is strongly
      influenced by household socio-economic characteristics, neighbourhood resources
      (facilities and social networks) will promote health care among the poorest and
      reduce access inequalities. Without being a key factor, the neighbourhood of
      residence-when it provides resources-may be of some help to overcome the
      financial hurdle. Findings suggest that the neighbourhood (local setting) is a
      relevant scale for health programmes in African cities. 

PMID- 25769740
TI  - Long-term survival of a semi-constrained implant following revision for
      infection.
AB  - Revision total knee arthroplasty (TKA) in prosthetic joint infections (PJI) is a
      challenging problem. We evaluated our institutional experience with a semi
      constrained implant placed in a PJI setting. Seventy-eight TKAs in 75 patients
      with a history of a PJI were identified. The average follow-up was 7.5 years.
      Twenty-three (29%) underwent repeat revision surgery. Five and 10 year survivals
      were 71% and 64%, respectively. The most common reason for repeat revision
      surgery was recurrent infection (78%). Smoking and elevated BMI increased the
      risk of repeat revision surgery. Significant improvements were maintained long
      term in pain and range of motion (P < 0.01 and P = 0.02). In the absence of
      repeat infection, long term pain relief and improved function may be expected
      with the semi-constrained implant.

PMID- 25769741
TI  - In reply to a letter "Not all continuous femoral nerve blocks are equivalent".

PMID- 25769742
TI  - Influence of Dexmedetomidine on the Tourniquet Related Responses in Hypertension
      Patients Receiving Unilateral Knee Arthroplasty under General Anesthesia.
AB  - This study aimed to investigate the influence of dexmedetomidine (DEX) on the
      tourniquet related responses in hypertension patients receiving unilateral knee
      arthroplasty (UKA) under general anesthesia. Results showed that the incidence of
      tourniquet induced hypertension (TIH), hemodynamics, MAC and EtSEV in DEX group
      were significantly lower than those in control group, regardless of hypertension.
      However, significant differences in TIH, hemodynamics, minimum alveolar
      concentration (MAC) and end-tidal sevoflurane (EtSEV) were not observed between
      hypertension patients and non-hypertension patients in both control group and DEX
      group. Moreover, oxygen index (OI) and respiratory index (RI) remained unchanged
      after deflation and DEX failed to affect OI and RI within 30 min after deflation,
      regardless of hypertension. Taken together, DEX may significantly improve the
      hemodynamics, which is independent of pre-existing hypertension.

PMID- 25769743
TI  - Birmingham Hip Resurfacing: A Single Surgeon Series Reported at a Minimum of 10
      Years Follow-Up.
AB  - We report outcomes on 120 Birmingham Hip Resurfacings (BHRs) (mean age 50 years)
      at a minimum of ten-years follow-up. Cases were performed by one surgeon and
      included his learning curve. Six hips were revised, with no revisions for
      infection, dislocation, or adverse reaction to metal debris. Ten-year survival
      was 94.2% (95% confidence interval (CI) 88.8%-98.7%) for all revisions and 96.1%
      (95% CI 91.5%-99.8%) for revisions for aseptic loosening. Gender (P = 0.463) and
      head size (P = 0.114) did not affect revision risk. Mean post-operative Harris
      hip score was 84.0. Contrary to previous independent reports, good outcomes into
      the second decade were achieved with the BHR in both men and women. Longer term
      follow-up will confirm whether these promising outcomes in women continue. 

PMID- 25769744
TI  - Total Hip Arthroplasty for Failed Internal Fixation After Femoral Neck Fracture
      Versus That for Acute Displaced Femoral Neck Fracture: A Comparative Study.
AB  - The outcome of total hip arthroplasty (THA) for failed internal fixation after
      femoral neck fracture (FNF) versus that for acute displaced femoral neck fracture
      is still controversial. This study retrospectively analyzed a consecutive series
      of 130 THAs for acute displaced FNF (64, group I) and for failed internal
      fixation (66, group II). Results showed THAs in group II were more technically
      demanding procedures with longer operative time and larger amounts of drainage
      compared to that in group I. Furthermore, multivariate analysis revealed that the
      associations between THAs (group II) and hip complications were notable (OR=4.15,
      P=0.017). These increased risks should be paid much attention to, not only for
      choosing the appropriate treatment option, but also for providing effective
      perioperative care. 

PMID- 25769745
TI  - Alcohol Misuse is an Independent Risk Factor for Poorer Postoperative Outcomes
      Following Primary Total Hip and Total Knee Arthroplasty.
AB  - The influence of alcohol misuse on outcomes following primary total hip (THA) or
      knee (TKA) arthroplasty is poorly understood. Using the National Hospital
      Discharge Survey, a cohort representative of 8,372,232 patients (without
      cirrhosis) who underwent THA or TKA between 1990 and 2007 was identified and
      divided into two groups: (1) those who misused alcohol (n=50,861) and (2) those
      who did not (n=8,321,371). Differences in discharge status, comorbidities and
      perioperative complications were analyzed. Compared to patients with no diagnosis
      of alcohol misuse, alcohol misusers were nine times more likely to leave against
      medical advice and had longer hospital stays (P<0.001). Alcohol misuse was
      independently associated with higher odds of in hospital complications (OR:
      1.334, range: 1.307-1.361), surgery related complications (OR: 1.293, range:
      1.218-1.373) and general medical complications (OR: 1.300, range: 1.273-1.327). 

PMID- 25769746
TI  - Reduced-Sodium Lunches Are Well-Accepted by Uninformed Consumers Over a 3-Week
      Period and Result in Decreased Daily Dietary Sodium Intakes: A Randomized
      Controlled Trial.
AB  - BACKGROUND: Processed foods are major contributors to excessive sodium intake in
      Western populations. We investigated the effect of food reformulation on daily
      dietary sodium intake. OBJECTIVE: To determine whether uninformed consumers
      accept reduced-sodium lunches and to determine the effect of consuming reduced
      sodium lunches on 24-hour urinary sodium excretion. DESIGN: A single-blind
      randomized controlled pretest-posttest design with two parallel treatment groups
      was used. PARTICIPANTS/SETTING: Participants chose foods in an experimental real
      life canteen setting at the Restaurant of the Future in Wageningen, the
      Netherlands, from May 16 until July 1, 2011. INTERVENTION: After a run-in period
      with regular foods for both groups, the intervention group (n=36) consumed foods
      with 29% to 61% sodium reduction (some were partially flavor compensated). The
      control group (n=38) continued consuming regular foods. MAIN OUTCOME MEASURES:
      Outcomes for assessment of acceptance were the amount of foods consumed, energy
      and sodium intake, remembered food liking, and intensity of sensory aspects.
      Influence on daily dietary sodium intake was assessed by 24-hour urinary sodium
      excretion. STATISTICAL ANALYSES PERFORMED: Between and within-subject comparisons
      were assessed by analysis of covariance. RESULTS: Energy intake and amount
      consumed of each food category per lunch remained similar for both groups.
      Compared with the control group, the intervention group's sodium intake per lunch
      was significantly reduced by -1,093 mg (adjusted difference) (95% CI -1,285 to 
      901), equivalent to 43 mmol sodium. Remembered food liking, taste intensity, and
      saltiness were scored similarly for almost all of the reduced-sodium foods
      compared with the regular foods. After consuming reduced-sodium lunches, compared
      with the control group, intervention participants' 24-hour urinary sodium
      excretion was significantly lower by -40 mEq (adjusted difference) (95% CI -63 to
      -16) than after consuming regular lunches, and this reflects a decreased daily
      sodium intake of 1 g. CONCLUSIONS: Comparing the two treatment groups,
      consumption of reduced-sodium foods over a 3-week period was well accepted by the
      uninformed participants in an experimental real-life canteen setting. The reduced
      sodium foods did not trigger compensation behavior during the remainder of the
      day in the intervention group compared with the control group, as reflected by 24
      hour urinary sodium excretion. Therefore, offering reduced-sodium foods without
      explicitly informing consumers of the sodium reduction can contribute to daily
      sodium intake reduction.

PMID- 25769747
TI  - Snacking behaviors, diet quality, and body mass index in a community sample of
      working adults.
AB  - BACKGROUND: Snacking behaviors have been linked with higher energy intake and
      excess weight. However, results have been inconsistent. In addition, few data are
      available on the extent to which snacking affects diet quality. OBJECTIVE: This
      study describes snacking behaviors, including total snacking energy, frequency,
      time of day, and percentage of snacking energy intake by food groups, and their
      associations with diet quality and body mass index (BMI; calculated as kg/m(2)).
      DESIGN: Snacking behaviors and dietary intake were examined cross-sectionally
      among 233 adults participating in a community-based worksite nutrition
      intervention from September 2010 through February 2013. Three telephone
      administered 24-hour dietary recalls were collected (2 weekdays; 1 weekend day).
      Diet quality was characterized by the Healthy Eating Index 2010 and BMI was
      computed using measured height and weight. SETTING: The setting was a large
      metropolitan medical complex in Minneapolis, Minnesota. MAIN OUTCOME MEASURES:
      Outcome measures included diet quality and BMI. STATISTICAL ANALYSES: General
      linear regression models were used to examine associations between each of the
      snacking behaviors as independent variables, and diet quality and BMI as
      dependent variables. RESULTS: Percent of snacking energy from fruit and juice
      (beta=.13; P=0.001) and nuts (beta=.16; P=0.008) were significantly positively
      associated with diet quality. Percent of snacking energy from desserts and sweets
      (beta=-.16; P<0.001) and sugar-sweetened beverages (beta=-.22; P=0.024) were
      significantly inversely associated. Percent of snacking energy from vegetables
      (beta=-.18; P=0.044) was significantly associated with lower BMI. Percent
      snacking energy from desserts and sweets was significantly associated with a
      higher BMI (beta=.04; P=0.017). CONCLUSIONS: Snack food choices, but not total
      energy from snacks, frequency, or time of day, were significantly associated with
      diet quality and BMI.

PMID- 25769748
TI  - Associations between depressive symptomatology, diet, and body mass index among
      participants in the supplemental nutrition assistance program.
AB  - BACKGROUND: Participation in the Supplemental Nutrition Assistance Program (SNAP)
      has been shown to increase food security, or access to adequate food; however,
      SNAP participation has also been associated with obesity among certain
      demographic groups (eg, women, but not men and children), possibly due to poorer
      dietary quality. Depressive symptomatology is an understudied factor, which is
      associated with obesity across the lifespan. OBJECTIVE: This study examined the
      relationship between depressive symptomatology, dietary quality, and body weight
      among a sample of SNAP participants (n=639). DESIGN: The analysis was cross
      sectional; survey data were collected in May to December 2011 by trained data
      collectors. PARTICIPANTS/SETTING: Adults who self-identified as the primary food
      shopper of the household in two predominantly low-income African-American
      neighborhoods characterized as "food deserts" in Pittsburgh, PA, were recruited
      to participate in this study. MEASURES: Dietary quality was calculated using the
      US Department of Agriculture's Healthy Eating Index-2005. Body mass index (BMI;
      calculated as kg/m(2)) was based on objective measurements taken by the
      interviewer. Current depressive symptomatology was assessed by a trained
      interviewer using the Patient Health Questionnaire-2. STATISTICAL ANALYSES
      PERFORMED: Descriptive statistics (means and percentages); two multivariate
      ordinary least-square regression analyses predicting BMI and dietary quality from
      depressive symptomatology while controlling for sociodemographic factors and food
      insecurity were performed. RESULTS: Depression was a strong and statistically
      significant predictor of both dietary quality and BMI; higher score in depressive
      symptomatology was associated with lower scores in dietary quality (beta=-1.26;
      P<0.0001). A higher score in depressive symptomatology was associated with higher
      BMI (beta=.63; P=0.0031). CONCLUSIONS: These findings show that depressive
      symptomatology is significantly associated with weight-related outcomes and
      suggests that understanding the risk of depression among SNAP participants could
      be important to understanding the relationships among SNAP participation, diet,
      and weight. The association between depressive symptomology, elevated BMI, and
      lower dietary quality among low-income, primarily African-American residents
      living in a food desert suggests the potential for mental health interventions to
      have broader benefits in this population. However, the directionality of this
      association is unclear and improving diet and reducing weight might also improve
      mental health symptoms. Additional longitudinal studies should assess these
      possibilities.

PMID- 25769749
TI  - Association of Prepregnancy Dietary Patterns and Anxiety Symptoms from
      Midpregnancy to Early Postpartum in a Prospective Cohort of Brazilian Women.
AB  - BACKGROUND: Adherence to unhealthy dietary patterns may alter the risk of mental
      disorders during pregnancy and the postpartum period. OBJECTIVE: To analyze the
      association between prepregnancy dietary patterns and prospective variations on
      anxiety symptoms from midpregnancy to early postpartum. METHODS: A prospective
      cohort of 207 healthy pregnant women was followed at 5 to 13, 20 to 26, and 30 to
      36 gestational weeks, and once at 30 to 45 days postpartum. The State-Trait
      Anxiety Inventory was used to evaluate anxiety symptoms at the second and third
      gestational trimesters and during the postpartum period. Dietary intake was
      assessed using a food frequency questionnaire administered during the first
      trimester of pregnancy that referred to the 6 months before pregnancy. Principal
      components analysis was used to identify dietary patterns and three prepregnancy
      dietary patterns were identified: common-Brazilian, healthy, and processed. Three
      longitudinal mixed-effect models were estimated to verify the association between
      dietary patterns and anxiety symptoms, adjusted for confounding variables.
      RESULTS: The mean anxiety symptom scores were 40.4, 40.5, and 37.2 for the second
      trimester, third trimester, and postpartum, respectively. The rate of variation
      of the State-Trait Anxiety Inventory score was 0.535 (95% CI -0.035 to 1.107;
      P=0.066) and -0.010 (95% CI -0.018 to -0.002; P=0.019) when accounting for
      gestational age and quadratic gestational age, respectively. The common-Brazilian
      pattern, comprised mainly of rice and beans (beta=-1.200, 95% CI -2.220 to 
      0.181; P=0.021), and the healthy pattern comprised mostly of vegetables, fruits,
      fish, and tea (beta=-1.290, 95% CI -2.438 to -0.134; P=0.029), were negatively
      associated with prospective changes in anxiety symptoms. CONCLUSIONS: High
      adherence to the common-Brazilian or healthy patterns was negatively associated
      with higher anxiety symptom scores from mid-pregnancy to early postpartum in this
      group of Brazilian women.

PMID- 25769751
TI  - The experience of Ugandan nurses in the practice of universal precautions.
AB  - In Uganda, nurses do not always practice universal precautions unless they know
      the patients' HIV status. In our study, focused ethnography was used to explore
      the experiences of Ugandan nurses in the practice of universal precautions while
      caring for persons living with HIV. In-depth interviews were completed with 16
      participants from a variety of units at a large teaching hospital in Uganda.
      Although participants were knowledgeable about universal precautions, the primary
      challenge to the practice of universal precautions was the inadequate supply of
      resources, both material and human. Despite challenges, the nurses displayed an
      enthusiasm for their work and a dedication to provide the best possible care for
      patients. The findings highlight the urgent need for governments and
      institutions, particularly in resource-constrained countries, to develop and
      implement policies related to universal precaution practice and to provide a
      consistent supply of protective equipment to ensure that universal precautions
      are consistently used. 

PMID- 25769750
TI  - Maternal HIV, substance use role modeling, and adolescent girls' alcohol use.
AB  - Parental role modeling has a major influence on adolescent alcohol use. Our study
      examined maternal factors associated with daughters' alcohol use among inner-city
      racial minority adolescents of HIV-infected and HIV-uninfected mothers. A
      nonprobability sample of 176 mothers (37% with HIV) and their adolescent
      daughters completed self-administered surveys. Between- and within-group analyses
      were conducted using hierarchical multivariate logistic regressions. Findings
      showed that in the full sample, difficulty talking with daughters about alcohol
      was positively associated with alcohol use among daughters, whereas maternal
      report of importance of religion was negatively associated with alcohol use among
      daughters. Within-group analysis of participants by maternal HIV status revealed
      that maternal beliefs that drinking alcohol in front of their daughters was
      normative were associated with higher odds of adolescent alcohol use in
      households with HIV-infected mothers. These preliminary findings highlight the
      potential increased vulnerability of racial minority adolescent girls living in
      households with HIV-infected mothers.

PMID- 25769752
TI  - Stigma in HIV-infected health care workers in Kenya: a mixed-method approach.
AB  - HIV-related stigma decreases access to HIV testing, prevention, and treatment
      services. Our mixed methods study explored stigma as perceived, experienced, and
      managed in a sample of 76 HIV-infected health care workers in Kisumu, Kenya.
      Stigma was quantitatively measured using the HIV/AIDS Stigma Instrument for
      People Living with AIDS (HASI-P). Overall, subjects experienced low stigma levels
      (mean = 7.88, SD = 12.90; range = 0-61), and none of the sociodemographic
      variables were predictive of stigma. Transcript analysis of 20 qualitative
      interviews revealed two negative themes (blame, lack of knowledge) and five
      positive themes (living positively, optimism, empathy, support, changes over
      time). Three themes emerged on reducing stigma (normalizing, empowerment, leading
      by example). Disclosure, access to treatment, stigma reduction training,
      workplace support groups, and awareness of an HIV workplace policy may have
      contributed to low stigma scores. Qualitative findings corroborated quantitative
      findings and corresponded to the six domains of the HASI-P. 

PMID- 25769753
TI  - The meaning and perceived value of mind-body practices for people living with
      HIV: a qualitative synthesis.
AB  - Mind-body practices (MBPs) are a subset of complementary medicine that represents
      a selection of self-care activities that may promote the health of people living
      with HIV (PLWH). No synthesis of qualitative research in this context, which
      might inform service provision and research priorities, has yet been published. A
      systematic search of electronic databases was conducted, identifying papers
      exploring the experience of MBPs in PLWH. During thematic synthesis, all text
      under the headings "results" or "findings" was scanned line by line, and
      discrete, meaningful units of text were extracted as data items. Categories were
      identified, and second- and third-order constructs were developed. Concerns
      related to control and self-management appeared in the convergence of
      participants' worlds with the medical world and in being pragmatic about
      selecting MBPs and goal setting. The themes developed suggest a desire for more
      holistic and person-centered care, arguably marginalized as a result of effective
      antiretroviral therapy. 

PMID- 25769754
TI  - Pap test adherence, cervical cancer perceptions, and HPV knowledge among HIV
      infected women in a community health setting.
AB  - The Health Belief Model (HBM) has been widely used as a framework to explain
      health behaviors in diverse populations, but little HBM research has focused on
      HIV-infected women and their increased risks for cervical cancer. We used
      Champion's Health Belief Model and Self-Efficacy scales to assess relationships
      between Pap test adherence and constructs of the HBM among 300 HIV-infected
      women. In addition, we assessed the relationship between HPV and cervical cancer
      knowledge and key HBM concepts. Participants reported low levels of knowledge
      regarding risk for cervical cancer and HPV. They perceived lower personal risk
      for cervical cancer. Women with higher perceived self-efficacy and lower
      perceived barrier scores reported better Pap test adherence. Findings indicate
      that HIV-infected women are not aware of the risk for cervical cancer and may not
      take preventive actions. Further research is needed to identify the full range of
      factors that impact adherence to cervical cancer screening. 

PMID- 25769755
TI  - Predictors of women's intentions to be screened for HIV during pregnancy.
AB  - Detection of HIV during pregnancy and consequent treatment may reduce harm to the
      fetus. We examine whether the combination of Health Belief Model and Theory of
      Planned Behavior predicts women's intentions to be screened for HIV during
      pregnancy. Two hundred Israeli women who participated in birth preparation
      classes completed e-mailed questionnaires. The results of a multiple linear
      regression reveal that perceived susceptibility to HIV, perceived benefits of
      screening, perceived severity of the illness, health motivation, and normative
      beliefs predicted women's intentions to be screened, while normative beliefs
      (beliefs about the extent to which significant others think they should be
      screened for HIV during pregnancy) was the most significant factor. Strategies to
      increase women's decision to be screened should address "significant others."
      Additionally, strategies should include promoting women's awareness of the risk
      of contracting HIV while emphasizing the benefits of the test and promoting a
      healthy lifestyle. 

PMID- 25769756
TI  - Nurses can facilitate safer sexual behavior counseling for persons living with
      HIV: strategies for success.

PMID- 25769757
TI  - Children Seeking Refuge: A Review of the Escalating Humanitarian Crisis of Child
      Sexual Abuse and HIV/AIDS in Latin America.
AB  - Early identification and intervention for victims of child sexual abuse (CSA) is
      essential to halting the spread of HIV in Latino populations because children who
      are sexually abused are at an increased risk of contracting HIV. The recent
      influx of unaccompanied children into the United States exposed histories of
      victimization, vulnerability to CSA, and suggested an epidemic of CSA in Latin
      America. CSA has been identified as a contributory event to HIV infection. The
      aim of our research was to identify factors associated with CSA and Latin
      Americans. A systematic review and a document search were conducted on factors
      associated with CSA in Latin America. Victimization was associated with lifelong
      risk factors for HIV. Males were consistently underrepresented in the published
      CSA literature and machismo attitudes may contribute to abuses of sexual power by
      males and contribute to males not reporting or under-reporting victimization. 

PMID- 25769758
TI  - Knowledge, Self-efficacy, and Self-perceived Risk for Cardiovascular Disease
      among Asians Living With HIV: The Influence of HIV Stigma and Acculturation.
AB  - Cardiovascular disease (CVD) and acute coronary syndrome (ACS) have become major
      health concerns for people living with HIV (PLWH) as life expectancy has
      increased with antiretroviral therapy. Studies suggest that motivation to seek
      health care is associated with knowledge, self-efficacy to engage in the health
      care system, and self-perceived risks for CVD and ACS. Using cross-sectional data
      collected from 67 un-/under-insured Asian PLWH in California, we explored the
      levels of knowledge about CVD, self-efficacy for recognizing ACS symptoms and
      seeking health care, and self-perceived risk for CVD and ACS, and how HIV
      stigmatization and acculturation predict these three constructs. Our sample had
      limited knowledge and low self-perceived risk but had high self-efficacy.
      Stigmatization was negatively correlated with self-efficacy (p = .004) and
      acculturation was a positive predictor of knowledge (p = .013). Economically
      vulnerable Asian PLWH need culturally appropriate interventions to improve their
      knowledge and self-perceived risks for CVD and ACS. 

PMID- 25769759
TI  - Coping With Stress Strategies in HIV-infected Iranian Patients.
AB  - Stress has significant adverse impacts on health outcomes of HIV-infected
      patients. Our study explored coping with stress strategies by HIV-infected
      Iranian patients. A qualitative content analysis study was conducted at the
      Consultation Clinic of HIV at the Imam Khomeini Hospital in Tehran, Iran in 2012.
      Twenty-six semi-structured in-depth interviews were done. Participants were asked
      about coping strategies for stress. After the first interview, continuous
      analysis of data was started and continued up to data saturation. Results showed
      that participants used two categories of strategies (emotion-based coping and
      problem-based coping) to cope with stress. Emotion-based coping had two sub
      themes: adaptive and maladaptive. The problem-based coping category had three sub
      themes: participation in education sessions, adherence to medication, and efforts
      to maintain a healthy lifestyle. Explanations of different strategies available
      to HIV-infected patients to cope with stress may help develop tailored
      interventions to improve the psychological conditions of people living with HIV. 

PMID- 25769760
TI  - [Psychotherapy and reality].

PMID- 25769761
TI  - [Progress, challenges and new perspectives in psychotherapy research in children
      and adolescents].

PMID- 25769762
TI  - [The AWMF-Guidelines for Hyperkinetic Disorders in therapeutic practice-
      knowledge, familiarity, utilization, and attitude of psychotherapists and
      physicians].
AB  - OBJECTIVE: The AWMF-Guidelines for Hyperkinetic Disorders (ADHD) provide
      psychotherapists and physicians with guidance concerning diagnostics and
      treatment for one of the most common disorders in children and adolescents. To
      date, however, it is unclear how these guidelines are being applied by practicing
      therapists (both physicians and psychotherapists) and what they consider to be
      its pros and cons. This study proposes (1) to analyze the differences between the
      estimation of ADHD-guidelines by users and nonusers, their corresponding
      attitudes, experiences, and evaluations of context factors; and (2) to analyze
      whether users and nonusers differ in their therapeutic practice. METHODS: 71
      therapists participated in a nonrepresentative online survey. RESULTS: The
      hypothesis was confirmed that, on average, users had a more positive attitude
      toward and experience with guideline-driven treatment than did nonusers. The
      results also show a small positive effect of guideline use on treatment quality.
      However, the methods employed by users and nonusers only moderately corresponded
      with the recommendations of the guidelines. CONCLUSIONS: It was shown that the
      ADHD guideline is only rarely being used, even under advantageous conditions, and
      that a practice-oriented form of the guideline does not exist until now.

PMID- 25769763
TI  - [The treatment needs of migrant children according to child and adolescent
      psychiatrists from medical clinics and in private practice].
AB  - OBJECTIVE: How does the German child and adolescent psychiatry system respond to
      the increasing number of migrant children and adolescents? METHOD: Senior doctors
      from German child and adolescent psychiatric hospitals (Association of Medical
      Hospital Directors in Child and Adolescent Psychiatry, Psychosomatics and
      Psychotherapy in Germany, BAG) completed a specially constructed questionnaire
      about the treatment needs of migrant children, while a "random, representative"
      sample of child and adolescent psychiatrists in private practice (German
      Professional Association for Child and Adolescent Psychiatry, Psychosomatic
      Medicine and Psychotherapy, BKJPP) was administered a slightly modified version.
      RESULTS: The 100 psychiatrists in private practice represented only about one
      eighth of their group, whereas the 55 medical directors comprised a
      representative sample. One-third of the hospitals has treatments tailored to the
      specific needs of migrants. In both settings, however, competent interpreters
      were rarely found, despite the treatment problems arising from the understanding
      the illness by the parents, language problems, and the clinical knowledge of the
      patient. Cultural diversity is perceived as enriching. The migration background
      and the sex of child and adolescent psychiatrists influence the treatment of
      migrants. CONCLUSION: Facilitating the process of "cultural opening" in child and
      adolescent psychiatry involves enacting concrete steps, such as the funding of
      interpreter costs.

PMID- 25769764
TI  - [Mindfulness-based intervention in attention-deficit-/hyperactivity disorder
      (ADHD)].
AB  - This paper reviews the current literature on mindfulness-based interventions in
      the treatment of attention-deficit/hyperactivity disorder (ADHD). Mindfulness
      means paying attention and being aware of the experiences occurring in the
      present moment, and it is usually developed by the practice of meditation.
      Research shows that mindfulness training is associated with improved attention
      systems and self-regulation, and that it therefore fosters those skills that are
      underdeveloped in individuals with ADHD. Although only few studies have
      investigated the effectiveness of mindfulness training in ADHD (many of which
      showing methodological limitations), the findings do suggest that mindfulness may
      be useful in ADHD interventions. 

PMID- 25769765
TI  - [Clinical diagnostics of ADHD in preschool-aged children].
AB  - Attention deficit hyperactivity disorder (ADHD) is one of the most prevalent
      psychiatric disorders in childhood and adolescence and has many negative
      consequences for both the child and the family. Early identification of children
      with ADHD would be helpful for the prevention of long-term consequences. This
      review appraises questionnaires and clinical interviews that can be used for the
      diagnosis of ADHD in preschool-aged children (3-5 years). We compare and discuss
      both German and international methods. The role of questionnaires and clinical
      interviews in the diagnostic process of ADHD is discussed. 

PMID- 25769771
TI  - Results with the Roseland((r)) HAC trapeziometacarpal prosthesis after more than
      10 years.
AB  - The Roseland((r)) hydroxyapatite-coated prosthesis is a total trapeziometacarpal
      joint prosthesis used for the surgical treatment of thumb basal joint arthritis.
      The aim of this retrospective study was to evaluate its long-term outcomes. Fifty
      one patients (64 thumbs) underwent trapeziometacarpal joint replacement with this
      prosthesis. The mean follow-up was 12.5 years. Survival rate of the prosthesis
      was 91%. There was either no pain or only occasional pain in 91% of cases. The
      mean QuickDASH score was 27.6. Abnormal radiographic findings were present in 70%
      of cases. Since they were often asymptomatic, no further treatment was carried
      out. Complications were common (25%) and occurred early on but could often be
      treated without surgery. The long-term results with the Roseland((r)) HAC
      prosthesis are satisfactory in terms of pain relief and function. However, the
      high complication rate is a major concern.

PMID- 25769772
TI  - Floating thumb metacarpal in a motorcyclist: A case report.
AB  - We present a case of simultaneous dislocation of the carpometacarpal and the
      metacarpophalangeal joints of the thumb (floating thumb metacarpal) in a 47-year
      old motorcyclist. The treatment consisted of closed reduction of both joints with
      cast immobilization. After 24 months, the functional result was excellent. The
      mechanism of this rare injury and its therapeutic management are discussed.

PMID- 25769773
TI  - Use of trifurcate arch graft in left ventricular assist device implantation via
      the sternal sparing approach.

PMID- 25769774
TI  - Safe sternal reentry in the setting of a giant aortic pseudoaneurysm and aortic
      regurgitation.

PMID- 25769775
TI  - The Freedom Solo pericardial stentless valve: Single-center experience, outcomes,
      and long-term durability.
AB  - OBJECTIVES: To report our institutional experience and long-term results with the
      Freedom Solo bovine pericardial stentless bioprosthesis (Sorin Group, Saluggia,
      Italy). METHODS: Between January 2005 and November 2009, 149 patients (mean age,
      73.6 +/- 8.7 years; 68 [45.6%] female) underwent isolated (n = 75) or combined (n
      = 74) aortic valve replacement (AVR) using the Solo in our institution. Follow-up
      was 100% complete with an average follow-up time of 5.9 +/- 2.6 years (maximum,
      9.6 years) and a total of 885.3 patient years. RESULTS: Operative (30-day)
      mortality was 2.7% (1.3% for isolated AVR [n = 1] and 4.0% for combined
      procedures [n = 3]). All causes of death were not valve-related. Preoperative
      peak (mean) gradients of 74.2 +/- 23.0 mm Hg (48.6 +/- 16.3 mm Hg) decreased to
      15.6 +/- 5.4 mm Hg (8.8 +/- 3.0 mm Hg) after AVR, and remained low for up to 9
      years. The postoperative effective orifice area was 1.6 +/- 0.57 cm(2), 1.90 +/-
      0.45 cm(2), 2.12 +/- 0.48 cm(2), and 2.20 +/- 0.66 cm(2) for the valve sizes 21,
      23, 25, and 27, respectively, with absence of severe prosthesis-patient mismatch
      and 0.7% (n = 1) experienced moderate prosthesis-patient mismatch. During follow
      up, 26 patients experienced structural valve deterioration (SVD) and 14 patients
      underwent explantation. Kaplan-Meier estimates for freedom from death,
      explantation, and SVD at 9 years averaged 0.57 (range, 0.47-0.66), 0.82 (range,
      0.69-0.90), and 0.70 (range, 0.57-0.79), respectively. CONCLUSIONS: The Freedom
      Solo stentless aortic valve is safe to implant and shows excellent early and
      midterm hemodynamic performance. However, SVD was observed in a substantial
      number of patients after only 5-6 years and the need for explantation increased
      markedly, suggesting low durability.

PMID- 25769776
TI  - Pertinent postpericardiotomy syndrome specifics.

PMID- 25769777
TI  - Comparison of postoperative quality of life for patients who undergo atrial
      myxoma excision with robotically assisted versus conventional surgery.
AB  - BACKGROUND: Robotically assisted cardiac surgery is an alternative to
      conventional, open-chest surgery. Although studies have been done on the clinical
      effect, morbidity, and mortality of robotically assisted atrial myxoma excision,
      few have addressed surgical outcomes, such as pain, quality of life (QOL), and
      length of sick leave from work. In this study, our aim was to evaluate these
      clinical variables among patients after they undergo robotically assisted atrial
      myxoma excision surgery. METHODS: Between January 2007 and January 2013, a total
      of 93 patients underwent either conventional sternotomy or robotically assisted
      atrial myxoma excision in our unit. The 36-item Medical Outcomes Study Short Form
      Survey was used to assess the clinical outcomes in these patients
      postoperatively, at day 30 and 6 months. RESULTS: The QOL scores for 7 of 8
      variables in the robotically assisted group were significantly higher than those
      in the conventional group at postoperative day 30 (P < .05). The degree of pain
      and its influence on work or life was lower in the robotically assisted group (P
      < .05), and these patients returned to work after 0.9 +/- 0.1 months, whereas
      those in the conventional group needed a sick leave of 3.3 +/- 0.4 months.
      CONCLUSIONS: The level of restoration of normal QOL within 30 days after atrial
      myxoma surgery is excellent with the robotically assisted approach, which may
      enable early return to employment and satisfactory recovery.

PMID- 25769778
TI  - Hypermetabolic residual retroperitoneal mass after chemotherapy for primary
      seminoma.

PMID- 25769779
TI  - Editorial comment.

PMID- 25769780
TI  - Reply: To PMID 25769779.

PMID- 25769781
TI  - Oncologic Outcomes of Penile Cancer Treatment at a UK Supraregional Center.
AB  - OBJECTIVE: To report contemporary treatment outcomes of penile squamous cell
      carcinoma at a UK supraregional center, including patterns of therapy, oncologic
      results, and long-term survival. PATIENTS AND METHODS: Patients with squamous
      cell carcinoma treated during the period January 2000 to January 2011 were
      included. Records were reviewed to identify the mode of therapy (penile
      preserving or amputative surgery), pathology reports (reclassified according to
      the 2009 tumor-nodes-metastasis classification), recurrence patterns, and cancer
      specific survival (CSS). Kaplan-Meier plots were used for survival analyses.
      RESULTS: Two hundred three patients were identified with a median follow-up of 61
      months. At presentation, 165 patients (82%) were node negative, 31 (15%) were
      node positive, and 7 (3%) had metastatic disease. Management was penile
      preserving surgery (n = 99, 49%), partial penectomy (n = 49, 24%), radical
      penectomy (n = 48, 24%), and chemotherapy or radiotherapy for metastatic disease
      (n = 7, 3%). After organ-preserving surgery, the local recurrence rate was 18%
      (compared with 4% for amputative surgery), with 94% of recurrences occurring
      within 3 years. Histopathologic staging was as follows, with pTis (20%), pT1
      (27%), pT2 (27%), pT3 (7%), and pT4 (1%). Kaplan-Meier analysis showed a 5-year
      CSS of 85% and a 10-year CSS of 81%. Five-year CSS was noted to decrease with
      advancing stage with pN0 tumors (92%), N1 (73%), N2 (61%), N3 (33%), and M1 (0%;
      P <.0001). CONCLUSION: Supraregional penile cancer management has led to
      considerable clinical experience in our center over the past decade. Close follow
      up is vital to pick up local recurrence after penile-preserving surgery. Overall
      oncologic outcomes are good with a 5-year CSS of 85%.

PMID- 25769782
TI  - Missed Hospital Appointments of Patients Receiving Ranibizumab Therapy for
      Neovascular Age-Related Macular Degeneration.
AB  - INTRODUCTION: The aim of this study was to investigate the frequency and duration
      of missed hospital appointments (MHAs) in a consecutive cohort of patients
      treated with ranibizumab for neovascular age-related macular degeneration (nAMD)
      and to assess their impact on outcomes of therapy in a real-world clinical
      setting. METHODS: Retrospective, cross-sectional study of consecutive patients
      attending medical retina clinics for nAMD treatment with ranibizumab. RESULTS:
      Seventy-eight eyes of 78 patients met the inclusion criteria for data analysis.
      Mean age was 78 years with mean follow-up of 27 months. Mean visual acuity (VA)
      was 52 +/- 16 letters at baseline, 56 +/- 17 letters at year 1 and 58 +/- 16
      letters at year 2. At the end of the second year, 90% of the patients had lost
      <15 letters, 26% had gained >=15 letters and 10% had lost >=15 letters. Nineteen
      patients had at least one MHA (24%) over 2 years. There were 26 MHA episodes in
      total leading to a median duration of 79 days (range 35-159) between attended
      hospital visits. None of these MHAs occurred during the first 3 months after
      treatment initiation. Mean VA and central retinal thickness difference between 2
      years and baseline for the MHA group was not statistically different compared
      with the non-MHA group. CONCLUSIONS: Our data suggest that MHA may be a
      relatively common occurrence in AMD treatment clinics, but good outcomes of
      treatment can be achieved over 2 years despite missed hospital visits if patients
      are reviewed on average six times in the first year after an initial loading
      phase of three injections and nine times in the second year of treatment.

PMID- 25769783
TI  - Physicochemical and tablet properties of Cyperus alulatus rhizomes starch
      granules.
AB  - The starch extracted from rhizomes of Cyperus alulatus (CA) was characterized for
      its physicochemical, morphological and tableting properties. Rhizomes of CA yield
      a significant quantity of starch granules (CASG) i.e., 11.93%. CASG was
      characterized in terms of moisture, ash and amylose contents, solubility and
      swelling power, paste clarity and water retention capacity. The swelling power
      was found to be significantly improved with the increase in temperature. Scanning
      electron micrographs revealed that the granule's surface was smooth, the granules
      were spherical, mostly round, disc like, and the size range was 6.65-12.13 MUm.
      Finger print region in FTIR spectra confirmed its carbohydrate nature. The
      evaluated micromeritic properties of extracted granule's bulk density, tapped
      density, Carr's index, Hausner ratio, true density and porosity render unique
      practicability of CASG being used as an adjuvant in pharmaceutical solid dosage
      forms. Tablets prepared by using CASG showed higher mechanical strength and more
      disintegration time, which depicted the characteristic binding nature of the
      starch granules. As CASG is imparting better binding properties in less
      concentration and also it can be used in combination with the established
      starches to get the synergistic effect; this starch can be used commercially in
      the tablet preparation.

PMID- 25769784
TI  - Pharmacokinetic interactions between telaprevir and antiretroviral drugs in
      HIV/HCV-coinfected patients with advanced liver fibrosis and prior HCV non
      responders.
AB  - Complex drug-drug interactions have been reported with concurrent administration
      of telaprevir (TVR) and human immunodeficiency virus (HIV) protease inhibitors
      (PIs), leading to relevant limitations of the therapeutic options for patients
      coinfected with hepatitis C virus (HCV) and HIV. However, little is known about
      the pharmacokinetics and drug interactions between TVR and antiretrovirals in
      HIV/HCV-coinfected patients with advanced liver fibrosis. Here we report the
      pharmacokinetics of TVR and antiretrovirals in a cohort of HIV/HCV genotype 1
      coinfected patients with advanced liver fibrosis treated with TVR-based triple
      anti-HCV therapy. No significant differences were observed in the
      pharmacokinetics of atazanavir, amprenavir or tenofovir at baseline and at Day 15
      of TVR, whereas the AUC0-4h of darunavir was 36% lower in the presence of TVR
      (AUC0-4h 15007ngh/mL and 9563ngh/mL at baseline and at Day 15 of TVR
      administration, respectively). Noteworthy, the AUC0-4h, Cmin and Cmax of
      raltegravir were reduced by 61%, 50% and 64%, respectively. However, none of the
      patient's plasma levels of tenofovir, atazanavir, amprenavir or raltegravir
      declined below their minimum effective concentrations even in association with
      TVR, and no HIV treatment failure occurred. A non-significant trend for lower TVR
      exposure was seen in patients concomitantly given amprenavir versus those given
      atazanavir (AUC0-4h, 9840ngh/mL and 13345ngh/mL, respectively). In conclusion,
      this study highlighted the feasibility of maintaining the current antiretroviral
      regimen in HIV/HCV-coinfected patients, even when significant interactions with
      TVR are predictable, whenever a change of HIV PIs is not deemed appropriate. 

PMID- 25769785
TI  - Identification and characterisation of a novel plasmid-mediated quinolone
      resistance gene, qnrVC7, in Vibrio cholerae of seafood origin.

PMID- 25769786
TI  - Acquisition of extended-spectrum cephalosporin- and colistin-resistant Salmonella
      enterica subsp. enterica serotype Newport by pilgrims during Hajj.
AB  - Gatherings like the Hajj involving many people who travel from different parts of
      the world represent a risk for the acquisition and dissemination of infectious
      diseases. In this study, acquisition of multidrug-resistant (MDR) Salmonella spp.
      in 2013 Hajj pilgrims from Marseille, France, was investigated. In total, 267
      rectal swabs were collected from 129 participants before their departure and
      after their return from the pilgrimage as well as during the pilgrimage from
      patients with diarrhoea. Samples were screened for the presence of Salmonella
      using quantitative real-time PCR and culture. Whole-genome sequencing was
      performed to characterise one of the isolates, and the mechanism leading to
      colistin resistance was investigated. Six post-Hajj samples and one sample
      collected during a diarrhoea episode in Hajj were positive for Salmonella by real
      time PCR, with five Salmonella enterica belonging to several serotypes recovered
      by culture, whereas no pre-Hajj sample was positive. Two of the isolates belonged
      to the epidemic Newport serotype, were resistant to cephalosporins, gentamicin
      and colistin, and harboured the bla(CTX-M-2) gene and a 12-nucleotide deletion in
      the pmrB gene leading to colistin resistance. This study shows that pilgrims
      acquired Salmonella bacteria, including a novel MDR clone, during the Hajj
      pilgrimage. This calls for more improved public health surveillance during Hajj
      because Salmonella is one of the most common diarrhoea-causing bacteria
      worldwide. Therefore, returning pilgrims could disseminate MDR bacteria worldwide
      upon returning to their home countries.

PMID- 25769788
TI  - Susceptibility of anaerobes to fusidic acid and fosfomycin.

PMID- 25769787
TI  - Emergent and evolving antimicrobial resistance cassettes in community-associated
      fusidic acid and meticillin-resistant Staphylococcus aureus.
AB  - Fusidic acid is a topical and systemic antimicrobial used for the treatment of
      staphylococcal infections in hospitals and the community. Sales of fusidic acid
      and resistance rates among meticillin-resistant Staphylococcus aureus (MRSA)
      doubled between 1990 and 2001. For the following decade, fusidic acid resistance
      rates among isolates from Addenbrooke's Hospital (Cambridge, UK) were compared
      with national resistance rates from MRSA bacteraemia surveillance data and with
      antimicrobial sales data. Sales of fusidic acid remained relatively constant
      between 2002 and 2012, whilst fusidic acid resistance increased two- and four
      fold in MRSA bacteraemias nationally and in MRSA isolates from Cambridge,
      respectively. A subgroup of MRSA resistant only to fusidic acid increased after
      2006 by 5-fold amongst bacteraemias nationally and 17-fold (to 7.7% in 2012)
      amongst Cambridge MRSA isolates. All of the available local isolates from 2011 to
      2012 (n=23) were acquired in the community, were not related epidemiologically
      and belonged to multilocus sequence typing (MLST) groups ST1, 5, 8, 45 or 149 as
      revealed from analysis of whole-genome sequence data. All harboured the fusC gene
      on one of six distinct staphylococcal cassette chromosome (SCC) elements, four of
      which were dual-resistance chimeras that encoded beta-lactam and fusidic acid
      resistance. In summary, fusidic acid-resistant MRSA increased in prevalence
      during the 2000s with notable rises after 2006. The development of chimeric
      cassettes that confer dual resistance to beta-lactams and fusidic acid
      demonstrates that the genetics underpinning resistance in community-associated
      MRSA are evolving. 

PMID- 25769789
TI  - Quality compliance in the shift from cell transplantation to cell therapy in non
      pharma environments.
AB  - Along with academic and charitable organizations, transfusion centers have
      ventured into the stem cell field, with the aim of testing of novel cell-based
      therapeutics in a clinical setting for future marketing approval. The fact that
      quality management structures, which are required for compliance with good
      scientific practice regulations, were originally designed for product development
      in corporate environments represents a major challenge for many developers. In
      this Commentary, challenges that non-pharmaceutical institutions must overcome to
      translate cell-based products into clinical therapies will be discussed from a
      quality standpoint. Furthermore, our development experience for a mesenchymal
      stromal cell-based therapy will be shared as a case study. 

PMID- 25769790
TI  - Combined immunotherapy with whole tumor lysate-pulsed interleukin-15-activated
      dendritic cells and cucurbitacin I promotes strong CD8(+) T-cell responses and
      cures highly aggressive lymphoma.
AB  - BACKGROUND AIMS: Dendritic cell (DC)-based therapies could be important
      strategies for lymphoma treatment. METHODS: AKR/J mice with Dalton's lymphoma
      were treated with recombinant interleukin-15 (rIL-15)-activated autologous DCs
      and pulsed with whole tumor cell lysates in the presence or absence of suboptimal
      doses of the STAT3 inhibitor cucurbitacin I. One group of treated mice received
      an additional dose of rIL-15 to boost the DC-based adoptive cell therapy (ACT).
      Kaplan-Meier survival analysis and multiple immunologic and enzymatic parameters
      were assessed to demonstrate the efficacy of the vaccination protocol. RESULTS:
      Therapy with tumor lysate-pulsed, rIL-15-activated DCs plus cucurbitacin I
      significantly prolongs the survival of tumor-bearing mice but fails to provide a
      complete cure. Additional treatment of vaccinated mice with rIL-15 dramatically
      improves the therapeutic efficacy and provides a lifelong cure with no relapse.
      DCs derived from the surviving vaccinated mice regained their anti-tumor
      potential against the lymphoma cells with respect to growth inhibition and
      cytotoxicity. Both cluster of differentiation (CD)4(+) and CD8(+) T cells were
      mobilized in metastatic organs of successfully vaccinated mice in large numbers
      and demonstrated antigen-specific proliferation and tumor cell cytotoxicity. ACT
      also augments DC function by upregulating tumor necrosis factor-related apoptosis
      inducing ligand and tumor necrosis factor-alpha expression. In addition,
      combinatorial immunotherapy restores the levels of antioxidant enzymes and liver
      function enzyme activities that are severely repressed in untreated tumor-bearing
      mice. CONCLUSIONS: Effective vaccination for a complete cure against aggressive
      lymphoma requires DC-based ACT in combination with chemotherapy and cytokine
      therapy.

PMID- 25769792
TI  - RECQ4 selectively recognizes Holliday junctions.
AB  - The RECQ4 protein belongs to the RecQ helicase family, which plays crucial roles
      in genome maintenance. Mutations in the RECQ4 gene are associated with three
      insidious hereditary disorders: Rothmund-Thomson, Baller-Gerold, and RAPADILINO
      syndromes. These syndromes are characterized by growth deficiency, radial ray
      defects, red rashes, and higher predisposition to malignancy, especially
      osteosarcomas. Within the RecQ family, RECQ4 is the least characterized, and its
      role in DNA replication and repair remains unknown. We have identified several
      DNA binding sites within RECQ4. Two are located at the N-terminus and one is
      located within the conserved helicase domain. N-terminal domains probably
      cooperate with one another and promote the strong annealing activity of RECQ4.
      Surprisingly, the region spanning 322-400aa shows a very high affinity for
      branched DNA substrates, especially Holliday junctions. This study demonstrates
      biochemical activities of RECQ4 that could be involved in genome maintenance and
      suggest its possible role in processing replication and recombination
      intermediates. 

PMID- 25769791
TI  - Significance of nuclear p-mTOR expression in advanced oral squamous cell
      carcinoma with extracapsular extension of lymph node metastases.
AB  - OBJECTIVES: Traditional dichotomous extranodal extension (ENE) grading could not
      differentiate the risk of subsequent failure in advanced stage oral squamous cell
      carcinoma (OSCC) patients with ENE. This study investigated nuclear
      phosphorylated mammalian target of rapamycin (p-mTOR) expression in extranodal
      tumours and correlated this with clinical outcomes. MATERIALS AND METHODS: A
      total of 218 advanced stage OSCC patients with neck lymph node metastasis were
      enrolled. Paired paraffin-embedded primary tumour and metastatic lymph node
      sections were stained with antibody against p-mTOR. Tumours with moderate-to
      strong staining in ?50% of tumour cells were recorded as being positive p-mTOR
      expression. The correlation of nuclear p-mTOR expression in extranodal tumours
      with clinicopathologic parameters was analysed. RESULTS: Nuclear p-mTOR
      expression in primary and extranodal tumours was highly associated with a lower
      grade of differentiation. The 5-year disease-free survival (DFS) of the patients
      without ENE, with and without positive nuclear p-mTOR expression in extranodal
      tumours was 54.3%, 23.4% and 55.2%, respectively. The 5-year overall survival
      (OS) of the patients without ENE, with and without nuclear p-mTOR expression in
      extranodal tumours was 55%, 18.7% and 51.3%, respectively. The patients with
      nuclear p-mTOR expression in extranodal tumours had significantly worse regional
      and distant disease control. Multivariate analysis also confirmed that nuclear p
      mTOR expression in extranodal tumours was a significant independent adverse
      factor. CONCLUSION: Nuclear p-mTOR expression can be used as a prognostic
      indicator predictive of DFS and OS in advanced OSCC patients with ENE. There
      might be a possibility for targeted therapy in this group of patients.

PMID- 25769793
TI  - Clinical repercussions of introducing biological therapies: the well-controlled
      patient.

PMID- 25769794
TI  - Hematopoietic Stem Cell Transplantation for Multiple Myeloma: Guidelines from the
      American Society for Blood and Marrow Transplantation.
AB  - Therapeutic strategies for multiple myeloma (MM) have changed dramatically over
      the past decade. Thus, the role of hematopoietic stem cell transplantation (HCT)
      must be considered in the context of this evolution. In this evidence-based
      review, we have critically analyzed the data from the most recent clinical trials
      to better understand how to incorporate HCT and when HCT is indicated. We have
      provided our recommendations based on strength of evidence with the knowledge
      that ongoing clinical trials make this a dynamic field. Within this document, we
      discuss the decision to proceed with autologous HCT, factors to consider before
      proceeding to HCT, the role of tandem autologous HCT, post-HCT maintenance
      therapy, and the role of allogeneic HCT for patients with MM. 

PMID- 25769795
TI  - Domain-specific transition questions demonstrated higher validity than global
      transition questions as anchors for clinically important improvement.
AB  - OBJECTIVES: Estimates of minimal clinically important differences in health
      measures may be affected by the anchor used. We examined if domain-specific
      transition questions had higher construct validity than global health transition
      questions as anchors for measures in a given domain. STUDY DESIGN AND SETTING: In
      a prospective study of 249 patients with rheumatoid arthritis, we examined
      changes in pain, physical function, joint swelling, stiffness, fatigue, and
      depression with treatment. We related these changes to a domain-specific
      transition question, global arthritis transition question, and the Short Form-36
      (SF-36) health transition item. RESULTS: Changes in all six clinical measures
      were more highly correlated with the domain-specific transition questions than
      with the global arthritis question and SF-36 transition question. Discrimination
      between patients who improved or not was also better using domain-specific
      questions. Estimates of minimal clinically important improvement (MCII) differed
      with the anchor when these were based on mean changes. MCII estimates from
      receiver operating characteristic curve analysis were not influenced by the
      choice of anchor when anchors had high agreement. CONCLUSION: Domain-specific
      transition questions had higher construct validity as anchors for determining
      clinically important differences in health measures focused on a single domain
      than either global disease or general health transition questions.

PMID- 25769796
TI  - Reversible magnetic resonance imaging changes in a case of neuroleptic malignant
      syndrome.
AB  - Neuroleptic malignant syndrome (NMS) is a life-threatening neurologic emergency
      associated with the use of mainly typical antipsychotic drugs. It is
      characterized by fever, altered mental status, generalized rigidity, autonomic
      instability, myoclonus, raised creatine phosphokinase, rhabdomyolysis, and
      leukocytosis. Neuroimaging (brain computed tomography/magnetic resonance imaging
      [MRI]) is usually normal in most of the cases of NMS. Magnetic resonance imaging
      findings have not been well elucidated in NMS as yet. Very few cases have been
      reported worldwide. We herein, report a case of a 42-year-old patient of NMS, who
      presented to us with reversible changes in MRI brain. This case report highlights
      the possible MRI changes in NMS and their plausible mechanism.

PMID- 25769797
TI  - Independent evaluation of a simple clinical prediction rule to identify right
      ventricular dysfunction in patients with shortness of breath.
AB  - BACKGROUND: Many patients have unexplained persistent dyspnea after negative
      computed tomographic pulmonary angiography (CTPA). We hypothesized that many of
      these patients have isolated right ventricular (RV) dysfunction from treatable
      causes. We previously derived a clinical decision rule (CDR) for predicting RV
      dysfunction consisting of persistent dyspnea and normal CTPA, finding that 53% of
      CDR-positive patients had isolated RV dysfunction. Our goal is to validate this
      previously derived CDR by measuring the prevalence of RV dysfunction and outcomes
      in dyspneic emergency department patients. METHODS: A secondary analysis of a
      prospective observational multicenter study that enrolled patients presenting
      with suspected PE was performed. We included patients with persistent dyspnea, a
      nonsignificant CTPA, and formal echo performed. Right ventricular dysfunction was
      defined as RV hypokinesis and/or dilation with or without moderate to severe
      tricuspid regurgitation. RESULTS: A total of 7940 patients were enrolled. Two
      thousand six hundred sixteen patients were analyzed after excluding patients
      without persistent dyspnea and those with a significant finding on CTPA. One
      hundred ninety eight patients had echocardiography performed as standard care. Of
      those, 19% (95% confidence interval [CI], 14%-25%) and 33% (95% CI, 25%-42%)
      exhibited RV dysfunction and isolated RV dysfunction, respectively. Patients with
      isolated RV dysfunction or overload were more likely than those without RV
      dysfunction to have a return visit to the emergency department within 45 days for
      the same complaint (39% vs 18%; 95% CI of the difference, 4%-38%). CONCLUSION:
      This simple clinical prediction rule predicted a 33% prevalence of isolated RV
      dysfunction or overload. Patients with isolated RV dysfunction had higher
      recidivism rates and a trend toward worse outcomes.

PMID- 25769798
TI  - Successful cardiopulmonary cerebral resuscitation in patient with severe acute
      pancreatitis.
AB  - Severe acute pancreatitis (SAP) is a critical illness in clinical practice, which
      is characterized by intensive inflammatory response in the early phase and
      infected pancreatic necrosis in the later phase. Despite the knowledge of SAP and
      critical care support technology got significant progress in recent years, SAP
      still carries approximately 30%mortality rate. Some SAP patients also have many
      other kinds of underlying disease such as hyperlipidemia, hypertension, coronary
      atherosclerotic heart disease, and heart rhythm abnormalities, which are related
      to cardiopulmonary arrest to some extent. Thus, the incidence of unpredictive
      cardiopulmonary arrest is high. Recently, a SAP patient in our intensive care
      unit had sudden cardiac arrest. After 52 minutes of cardiopulmonary
      resuscitation, she had return of spontaneous circulation and regained
      consciousness within 2 hours. To our knowledge, there is no successful report
      after such long resuscitation in SAP patients. She was receiving continuous renal
      replacement therapy (CRRT) and continuous veno-venous hemofiltration, in the
      event of cardiopulmonary arrest. No study reported what kind of role CRRT can
      play when cardiac arrest occurs. Usually, we would stop existing CRRT when
      cardiac arrest occurred.We would not start CRRT for the complexity of operation
      and additional loss of blood. This time, we used CRRT to regulate electrolyte and
      acid-base imbalance and implement hypothermia brain protection, which played an
      important role in the patient that we report here.We strongly recommended a
      prolonged cardiopulmonary cerebral resuscitation in some not quite old SAP
      patients and continue to use existing CRRT but not remove it.

PMID- 25769800
TI  - Meet the editorial board.

PMID- 25769799
TI  - Carboxyhemoglobin and methemoglobin levels as prognostic markers in acute
      pulmonary embolism.
AB  - OBJECTIVES: Carboxyhemoglobin (COHb) and methemoglobin (MetHb) levels have been
      associated with a poor outcome in patients with various pathological conditions
      including cardiovascular diseases. Our aim was to retrospectively assess the
      prognostic value of arterial COHb and MetHb in patients with acute pulmonary
      embolism (PE). METHODS: We conducted a retrospective study of 156 patients
      admitted in a pulmonary clinic due to acute PE. Measured variables during
      emergency department evaluation that were retrospectively analyzed included the
      ratio of the partial pressure of oxygen in arterial blood to the fraction of
      oxygen in inspired gas, Acute Physiology and Chronic Health Evaluation II score,
      risk stratification indices, and arterial blood gases. The association between
      arterial COHb and MetHb levels and disease severity or mortality was evaluated
      using bivariate tests and logistic regression analysis. RESULTS: Arterial COHb
      and MetHb levels correlated with Acute Physiology and Chronic Health Evaluation
      II and pulmonary severity index scores. Furthermore, arterial COHb and MetHb
      levels were associated with troponin T and N-terminal pro-B-type natriuretic
      peptide levels. In univariate logistic regression analysis, COHb and MetHb levels
      were both significantly associated with an increased risk of death. However, in
      multivariate analysis, only COHb remained significant as an independent predictor
      of in-hospital mortality. CONCLUSION: Our preliminary data suggest that arterial
      COHb and MetHb levels reflect the severity of acute PE, whereas COHb levels are
      independent predictors of in hospital death in patients in this clinical setting.
      These findings require further prospective validation.

PMID- 25769801
TI  - HMGB1-binding heptamer suppresses the synergistic effect of HMGB1 and LPS by
      interacting directly with HMGB1.
AB  - High mobility group box 1 (HMGB1) is an endogenous danger signal molecule. In the
      postischemic brain, HMGB1 is massively released during acute damaging process and
      triggers inflammatory processes. Moreover, it has been reported HMGB1 augments
      the proinflammatory effect of LPS by direct interaction. In previous studies, the
      authors showed intranasally delivered a HMGB1 binding heptamer peptide (HBHP;
      HMSKPVQ) has robust neuroprotective effects in the ischemic brain after middle
      cerebral artery occlusion and that it exerts an anti-inflammatory effect. In the
      present study, the authors investigated whether HBHP suppresses the augmentation
      of the proinflammatory effect of LPS by HMGB1. In primary microglial cultures,
      low doses of LPS (5 ng/ml) and recombinant HMGB1 (rHMGB1, 20 ng/ml)
      synergistically activated microglial cells, and HMGB1-LPS binding was detected.
      In addition, synergistic NO accumulation along with direct HMGB1-LPS binding was
      also observed when primary microglial cultures were treated with LPS (5 ng/ml)
      and HMGB1 accumulated in NMDA-conditioned medium (NCM). Co-treatment of
      microglial cells with HBHP and LPS or rHMGB1 (NCM), or treatment with rHMGB1 or
      NCM and LPS after pre-incubating rHMGB1 (or NCM) with HBHP markedly suppressed
      their synergistic activation. Furthermore, interactions between rHMGB1 and LPS or
      between HMGB1 in NCM and LPS were suppressed dose-dependently by HBHP, indicating
      that HBHP suppressed the synergism between HMGB1 and LPS and the underlying
      mechanism involved inhibition of HMGB1-LPS binding. Together these results show
      HBHP has anti-inflammatory effects, and that it inhibits synergism caused by the
      binding of HMGB1 and LPS.

PMID- 25769802
TI  - Neuroprotective role of sphingosine-1-phosphate in L-BMAA treated neuroblastoma
      cells (SH-SY5Y).
AB  - Sphingosine-1-phosphate (S1P) is a bioactive lipid which regulates proliferation,
      cell migration, survival and differentiation by specific receptors activation. We
      studied its effects on L-BMAA treated neuroblastoma cells (SH-SY5Y), an amino
      acid that can trigger neurodegenerative diseases such as amyotrophic lateral
      sclerosis/Parkinson dementia complex (ALS/PDC). We found that S1P protects from
      necrosis and prevents the GSK3 increasing as long as the PI3K/AKT pathway is
      active. Moreover, GSK3 inhibition protects against neuronal death caused by L
      BMAA. 

PMID- 25769803
TI  - Establishment of reverse transcription loop-mediated isothermal amplification for
      rapid detection and differentiation of canine distemper virus infected and
      vaccinated animals.
AB  - Although widespread vaccination against canine distemper virus (CDV) has been
      conducted for many decades, several canine distemper outbreaks in vaccinated
      animals have been reported frequently. In order to detect and differentiate the
      wild-type and vaccine strains of the CDV from the vaccinated animals, a novel
      reverse transcription loop-mediated isothermal amplification (RT-LAMP) method was
      developed. A set of four primers-two internal and two external-were designed to
      target the H gene for the specific detection of wild-type CDV variants. The CDV-H
      RT-LAMP assay rapidly amplified the target gene, within 60 min, using a water
      bath held at a constant temperature of 65 degrees C. The assay was 100-fold more
      sensitive than conventional RT-PCR, with a detection limit of 10(-1)TCID50ml(-1).
      The system showed a preference for wild-type CDV, and exhibited less sensitivity
      to canine parvovirus, canine adenovirus type 1 and type 2, canine coronavirus,
      and canine parainfluenza virus. The assay was validated using 102 clinical
      samples obtained from vaccinated dog farms, and the results were comparable to a
      multiplex nested RT-PCR assay. The specific CDV-H RT-LAMP assay provides a
      simple, rapid, and sensitive tool for the detection of canines infected with wild
      type CDV from canines vaccinated with attenuated vaccine.

PMID- 25769805
TI  - Electrostatically driven lipid-protein interaction: Answers from FRET.
AB  - Electrostatics govern the association of a large number of proteins with cellular
      membranes. In some cases, these proteins present specialized lipid-binding
      modules or membrane targeting domains while in other cases association is
      achieved through nonspecific interaction of unstructured clusters of basic
      residues with negatively charged lipids. Given its spatial resolution in the
      nanometer range, Forster resonance energy transfer (FRET) is a powerful tool to
      give insight into protein-lipid interactions and provide molecular level
      information which is difficult to retrieve with other spectroscopic techniques.
      In this review we present and discuss the basic formalisms of both hetero- and
      homo-FRET pertinent to the most commonly encountered problems in lipid-protein
      interaction studies and highlight some examples of implementations of different
      FRET methodologies to characterize lipid/protein systems in which electrostatic
      interactions play a crucial role. This article is part of a Special Issue
      entitled: Lipid-protein interactions. 

PMID- 25769804
TI  - Genome-Wide Localization Study of Yeast Pex11 Identifies Peroxisome-Mitochondria
      Interactions through the ERMES Complex.
AB  - Pex11 is a peroxin that regulates the number of peroxisomes in eukaryotic cells.
      Recently, it was found that a mutation in one of the three mammalian paralogs,
      PEX11beta, results in a neurological disorder. The molecular function of Pex11,
      however, is not known. Saccharomyces cerevisiae Pex11 has been shown to recruit
      to peroxisomes the mitochondrial fission machinery, thus enabling proliferation
      of peroxisomes. This process is essential for efficient fatty acid beta
      oxidation. In this study, we used high-content microscopy on a genome-wide scale
      to determine the subcellular localization pattern of yeast Pex11 in all non
      essential gene deletion mutants, as well as in temperature-sensitive essential
      gene mutants. Pex11 localization and morphology of peroxisomes was profoundly
      affected by mutations in 104 different genes that were functionally classified. A
      group of genes encompassing MDM10, MDM12 and MDM34 that encode the mitochondrial
      and cytosolic components of the ERMES complex was analyzed in greater detail.
      Deletion of these genes caused a specifically altered Pex11 localization pattern,
      whereas deletion of MMM1, the gene encoding the fourth, endoplasmic-reticulum
      associated component of the complex, did not result in an altered Pex11
      localization or peroxisome morphology phenotype. Moreover, we found that Pex11
      and Mdm34 physically interact and that Pex11 plays a role in establishing the
      contact sites between peroxisomes and mitochondria through the ERMES complex.
      Based on these results, we propose that the mitochondrial/cytosolic components of
      the ERMES complex establish a direct interaction between mitochondria and
      peroxisomes through Pex11. 

PMID- 25769806
TI  - An antioxidant-like action for non-peroxidisable phospholipids using ferrous iron
      as a peroxidation initiator.
AB  - The degradation of phospholipids containing polyunsaturated fatty acids, termed
      peroxidation, poses a constant challenge to membranes lipid composition and
      function. Phospholipids with saturated (e.g. PC 16:0/16:0) and monounsaturated
      fatty acids (e.g. PC 16:0/18:1) are some of the most common phospholipids found
      in membranes and are generally not peroxidisable. The present experiments show
      that these non-peroxidisable phospholipids, when present in liposomes with
      peroxidisable phospholipids (i.e. those containing polyunsaturated fatty acids)
      such as PC 16:0/18:2 and Soy PC, produce an inhibitory effect on rates of
      peroxidation induced by ferrous-iron. This inhibitory effect acts to extend the
      duration of the lag phase by several-fold. If present in natural systems, this
      action could enhance the capacity of conventional antioxidant mechanisms in
      membranes. The results of this preliminary work suggest that non-peroxidisable
      phospholipids may exert an antioxidant-like action in membranes. 

PMID- 25769807
TI  - Response to Crizotinib in a Patient With Lung Adenocarcinoma Harboring a MET
      Splice Site Mutation.

PMID- 25769808
TI  - Increased interleukin 23 (IL23) levels in schizophrenia patients treated with
      depot antipsychotic medication.
AB  - BACKGROUND: Schizophrenia is a mental disorder, where genetic and environmental
      factors contribute to disease onset and progression. The immune system appears to
      play a role in schizophrenia, where altered cytokines levels and autoantibodies
      have been described. Notably however, to our knowledge, IL23 levels have not
      before been measured in schizophrenia patients treated with depot medication.
      METHODS: We examined IL23 levels in serum samples obtained from patients with
      schizophrenia, treated with depot medication (n=35) compared with healthy
      controls (n=38) and correlated these levels with treatment time, patient age and
      illness severity. RESULTS: IL23 levels were raised in depot treated groups
      compared with healthy controls. No correlation was observed, however, between
      IL23 levels and treatment time, patient age or illness severity. CONCLUSIONS:
      IL23 levels are raised in schizophrenia patients prescribed with depot
      medication, supporting the role of aberrant cytokine signalling in schizophrenia.

PMID- 25769809
TI  - Impaired immune response to Candida albicans in cells from Fanconi anemia
      patients.
AB  - Fanconi anemia (FA) is a genetic disorder characterized by bone marrow failure
      and cancer predisposition. Several studies show alterations of the immunological
      status of FA patients including defects in peripheral blood lymphocyte subsets,
      serum immunoglobulin levels, and inflammatory cytokines. However scanty
      information is available on the response of FA cells to specific infectious
      antigens. In this work we examined the response of FA cells to different
      immunological stimuli and found a defective response of IL-1beta, TNF-alpha and
      IL-17 to Candida albicans stimulation thus pointing to a potentially impaired
      response to fungal infections of FA patients. 

PMID- 25769810
TI  - Response to the Letter to editor regarding "Plastic bronchitis associated with
      influenza virus infection in children: a report on 14 cases".

PMID- 25769811
TI  - Internal jugular vein phlebectasia: A rare presentation.

PMID- 25769813
TI  - More than one way to be an herbivore: convergent evolution of herbivory using
      different digestive strategies in prickleback fishes (Stichaeidae).
AB  - In fishes, the evolution of herbivory has occured within a spectrum of digestive
      strategies, with two extremes on opposite ends: (i) a rate-maximization strategy
      characterized by high intake, rapid throughput of food through the gut, and
      little reliance on microbial digestion or (ii) a yield-maximization strategy
      characterized by measured intake, slower transit of food through the gut, and
      more of a reliance on microbial digestion in the hindgut. One of these strategies
      tends to be favored within a given clade of fishes. Here, we tested the
      hypothesis that rate or yield digestive strategies can arise in convergently
      evolved herbivores within a given lineage. In the family Stichaeidae, convergent
      evolution of herbivory occured in Cebidichthys violaceus and Xiphister mucosus,
      and despite nearly identical diets, these two species have different digestive
      physiologies. We found that C. violaceus has more digesta in its distal intestine
      than other gut regions, has comparatively high concentrations (>11 mM) of short
      chain fatty acids (SCFA, the endpoints of microbial fermentation) in its distal
      intestine, and a spike in beta-glucosidase activity in this gut region, findings
      that, when coupled to long retention times (>20 h) of food in the guts of C.
      violaceus, suggest a yield-maximizing strategy in this species. X. mucosus showed
      none of these features and was more similar to its sister taxon, the omnivorous
      Xiphister atropurpureus, in terms of digestive enzyme activities, gut content
      partitioning, and concentrations of SCFA in their distal intestines. We also
      contrasted these herbivores and omnivores with other sympatric stichaeid fishes,
      Phytichthys chirus (omnivore) and Anoplarchus purpurescens (carnivore), each of
      which had digestive physiologies consistent with the consumption of animal
      material. This study shows that rate- and yield-maximizing strategies can evolve
      in closely related fishes and suggests that resource partitioning can play out on
      the level of digestive physiology in sympatric, closely related herbivores.

PMID- 25769812
TI  - Seizure-related regulation of GABAA receptors in spontaneously epileptic rats.
AB  - In this study, we analyzed the impact that spontaneous seizures might have on the
      plasma membrane expression, composition and function of GABAA receptors
      (GABAARs). For this, the tissue of chronically epileptic rats was collected
      within 3h of seizure occurrence (<=3h group) or at least 24h after seizure
      occurrence (>=24h group). A retrospective analysis of seizure frequency revealed
      that selecting animals on the bases of seizure proximity also grouped animals in
      terms of overall seizure burden with a higher seizure burden observed in the <=3h
      group. A biochemical analysis showed that although animals with more
      frequent/recent seizures (<=3h group) had similar levels of GABAAR at the plasma
      membrane they showed deficits in inhibitory neurotransmission. By contrast, the
      tissue obtained from animals experiencing infrequent seizures (>=24h group) had
      increased plasma membrane levels of GABAAR and showed no deficit in inhibitory
      function. Together, our findings offer an initial insight into the molecular
      changes that might help to explain how alterations in GABAAR function can be
      associated with differential seizure burden. Our findings also suggest that
      increased plasma membrane levels of GABAAR might act as a compensatory mechanism
      to more effectively maintain inhibitory function, repress hyperexcitability and
      reduce seizure burden. This study is an initial step towards a fuller
      characterization of the molecular events that trigger alterations in GABAergic
      neurotransmission during chronic epilepsy. 

PMID- 25769814
TI  - Dirofilariasis by Dirofilaria repens: an imported case and a brief review.
AB  - Human infections caused by Dirofilaria repens, a cosmopolitan zoonotic
      parasitosis endemic in Southern and Eastern Europe and Asia still is an
      underdiagnosed infection due to parasite identification difficulties. Here, we
      report the first human case of subcutaneous dirofilariasis by D. repens diagnosed
      in Portugal. This was probably an imported case from India, as judged by
      epidemiological and clinical data. With this presentation we aim to alert
      clinicians for the emergence of vector-borne zoonoses associated with global
      warming and international travel. This case showed that differential diagnosis of
      D. repens in subcutaneous nodules is needed, in order to avoid further
      complications. 

PMID- 25769816
TI  - Pressure on emergency departments is having serious knock-on effect on hospital
      doctors' work, conference hears.

PMID- 25769815
TI  - Prediction of drug-ABC-transporter interaction--Recent advances and future
      challenges.
AB  - With the discovery of P-glycoprotein (P-gp), it became evident that ABC
      transporters play a vital role in bioavailability and toxicity of drugs. They
      prevent intracellular accumulation of toxic compounds, which renders them a major
      defense mechanism against xenotoxic compounds. Their expression in cells of all
      major barriers (intestine, blood-brain barrier, blood-placenta barrier) as well
      as in metabolic organs (liver, kidney) also explains their influence on the ADMET
      properties of drugs and drug candidates. Thus, in silico models for the
      prediction of the probability of a compound to interact with P-gp or analogous
      transporters are of high value in the early phase of the drug discovery process.
      Within this review, we highlight recent developments in the area, with a special
      focus on the molecular basis of drug-transporter interaction. In addition, with
      the recent availability of X-ray structures of several ABC-transporters, also
      structure-based design methods have been applied and will be addressed. 

PMID- 25769817
TI  - Chemical constituents from Kandelia candel with their inhibitory effects on pro
      inflammatory cytokines production in LPS-stimulated bone marrow-derived dendritic
      cells (BMDCs).
AB  - Chemical investigation of Kandelia candel resulted in the isolation of 19
      compounds (1-19), including one new sesquiterpene glycoside, kandelside (1),
      three megastigman glycoside compounds (7-9), 16 known phenolic compounds (2-6 and
      10-19). Structures of the isolated compounds were elucidated based on spectral
      data comparison with reported values. Isolated compounds were also evaluated for
      their inhibitory effects on the production of pro-inflammatory cytokines
      interleukin (IL)-12 p40, IL-6, and tumor necrosis factor alpha (TNF-alpha) in
      lipopolysaccharide (LPS)-stimulated bone marrow-derived dendritic cells. Among
      these compounds, compound 9 exhibited strong inhibitory activity against IL-6
      production (IC50=0.07 +/- 0.05 MUM) and moderate inhibitory activity against TNF
      alpha production (IC50=49.86 +/- 1.02 MUM), but exhibited no activity on IL-12
      p40 production. Compounds 5 and 6 significantly inhibited IL-12 p40, IL-6, and
      TNF-alpha production with IC50 values of 11.68 +/- 0.38, 44.52 +/- 1.08, and
      28.73 +/- 0.96 MUM, respectively.

PMID- 25769818
TI  - Tandem DNAzymes for mRNA cleavage: choice of enzyme, metal ions and the antisense
      effect.
AB  - The concept of DNAzyme-based gene silencing via mRNA cleavage was proposed over
      twenty years ago. A number of studies regarding intracellular gene silencing have
      been reported as well. However, questions have been raised regarding the lack of
      enzyme activity in physiological buffer conditions and it is being doubted that
      in the previously reported studies, gene silencing might be simply due to an
      antisense effect. In this work, two classical DNAzymes for RNA cleavage are
      studied using both chimeric substrates and extracted mRNA. We concluded that the
      activity of the 8-17 DNAzyme is much higher than that of 10-23 in the same
      conditions. To illustrate and compare the effect of specific cleavage versus
      antisense effect in the best possible way, we used tandem DNAzymes. Specific mRNA
      cleavage occurred with Zn(2+), while with Mg(2+), even the inactive control
      DNAzymes showed a similar response, suggesting that the antisense effect might be
      the dominating phenomenon causing gene silencing. This study has thus clarified
      the choice of DNAzyme sequence, the effect of metal ions and a potential source
      of antisense effect. 

PMID- 25769819
TI  - The role of G protein coupled receptor-mediated signaling in the biological
      properties of Acanthamoeba castellanii of the T4 genotype.
AB  - Despite advances in antimicrobial chemotherapy and supportive care, the prognosis
      of Acanthamoeba infections remains poor, suggesting that new targets are needed
      that can affect parasite survival and host-pathogen interactions. G proteins and
      their coupled receptors are well known regulators of a variety of cellular
      functions. The overall aim of the present study was to study the role of G
      protein coupled receptor, beta adrenergic receptor on the biology and
      pathogenesis of keratitis isolate of Acanthamoeba castellanii of the T4 genotype.
      Inhibition of beta adrenergic receptor using antagonist, propranolol had
      detrimental effects on the extracellular proteolytic activities A. castellanii as
      determined using zymographic assays. Conversely, beta adrenergic receptor
      agonist, isoprenaline showed increased proteases. Interestingly, beta adrenergic
      receptor inhibition affected A. castellanii growth (using amoebistatic assays),
      viability (using amoebicidal assays by measuring uptake of Trypan blue) and
      encystation as determined by trophozoite transformation into the cyst form. Pre
      treatment of parasites with propranolol hampered A. castellanii-mediated human
      brain microvascular endothelial cell cytotoxicity, as measured by the lacatate
      dehydrogenase release. The aforementioned findings suggest that G-protein coupled
      receptor, beta adrenergic receptor-mediated signaling in A. castellanii biology
      and pathogenesis may offer new pharmacological targets. 

PMID- 25769820
TI  - Molecular surveillance of candidemia due to Candida albicans among cancer
      patients during 2009 to 2013 by microsatellite typing.
AB  - BACKGROUND: Since the high morbidity and mortality of candidemia among cancer
      patients, the epidemiology has been underlined. In recent years, Candida species
      genotyping has been established, which could provide detail characteristics of
      epidemiology and has been underscored for candidemia preventing strategies.
      METHODS: Data of cancer patients with candidemia and hospitalized in Tianjin
      Medical University Cancer Institute and Hospital (TMUCIH) during 2009-2013 were
      reviewed. Species identification was carried out by using VITEK-2 Compact.
      Microsatellite typing was performed for molecular analysis. SPSS 20.0 and MVSP
      3.22 software were used for statistical and clustering analysis, respectively.
      RESULTS: Total of 36 isolates of Candida albicans were recovered from 36 cancer
      patients with nosocomial candidemia in TMUCIH during the period of 2009-2013
      included in the study. Total of 17 genotypes were identified and 2 of them were
      endemic genotypes, which caused 21 (58.3%) of 36 episodes of candidemia.
      Hepatobiliary oncology, ICU and gastrointestinal oncology were the main wards of
      infections due to endemic strains. Gastrointestinal cancer and insertion of a
      nasogastric tube were the predictors of infections caused by endemic strains (p =
      0.014 and p = 0.041, respectively). For the 36 cases, crude mortality was up to
      30.6%, and there was no significant difference between infections due to endemic
      and non-endemic strains (p = 0.077). CONCLUSIONS: This study proved that endemic
      stains of C. albicans could exist for a long period and mainly in a few wards.
      Patients with gastrointestinal cancer or nasogastric tube insertion were more
      sensitive to endemic C. albicans.

PMID- 25769821
TI  - Deciphering the protein interaction in adhesion of Francisella tularensis subsp.
      holarctica to the endothelial cells.
AB  - Extracellular form of Francisella is able to cross various cell barriers and
      invade multiple organs, such as skin, liver, lung and central nervous system.
      Transient adhesion of Francisella to endothelial cells may trigger the process of
      translocation. In this report, we showed that Francisella tularensis subsp.
      holarctica (Fth) is able to adhere to the endothelial cells, while ICAM-1 may
      serve as an adhesion molecule for Fth. Pull down and affinity ligand binding
      assays indicated that the PilE4 could be the probable ligand for ICAM-1. Further
      deciphering of this ligand:receptor interaction revealed that PilE4 interacts
      with Ig-like C2-type 1 domain of ICAM-1. To corroborate the role of PilE4 and
      ICAM-1 interaction in adhesion of extracellular form of Fth to endothelial cells,
      ICAM-1 was blocked with monoclonal anti-ICAM-1 antibody prior to the incubation
      with Fth and numbers of adherent bacteria were counted. Blocking of the ICAM-1
      significantly reduced (500-fold, P < 0.05) number of adherent Fth compared to
      unblocked cells. PilE4:ICAM-1 interaction unfolded here may provide a new
      perspective on molecules involved in the adhesion of extracellular form of
      Francisella to endothelial cells and probably its translocation across
      endothelial barriers. 

PMID- 25769823
TI  - Phylogenetic and functional alterations in bacterial community compositions in
      broiler ceca as a result of mannan oligosaccharide supplementation.
AB  - This study focused on identifying reproducible effects of dietary supplementation
      with a mannan oligosaccharide (MOS) on the broiler cecal bacterial community
      structure and function in a commercial production setting. Two separate trials,
      each with a control and a supplemented group, were carried out in the same
      commercial location and run concurrently. Approximately 10,000 birds from the
      same commercial hatchery were mirror imaged into each of four commercial broiler
      sheds and fed either a control or supplemented diet. Cecal contents were obtained
      on days 7, 21, and 35 posthatch from 12 randomly caught broilers from each group.
      Bacterial pyrosequencing was performed on all samples, with approximately 250,000
      sequences obtained per treatment per time point. The predominant phyla identified
      at all three time points in both trials were Firmicutes, Bacteroidetes,
      Proteobacteria, Actinobacteria, and Tenericutes, representing >99% of all
      sequences. MOS supplementation altered the bacterial community composition from 7
      days supplementation through 35 days supplementation. Bacteroidetes appeared to
      be replacing Firmicutes as a result of supplementation, with the most noticeable
      effects after 35 days. The effects of supplementation were reproducible across
      both trials. PICRUSt was used to identify differences between the functional
      potentials of the bacterial communities as a result of MOS supplementation. Using
      level 3 KEGG ortholog function predictions, differences between control and
      supplemented groups were observed, with very strong segregation noted on day 35
      posthatch in both trials. This indicated that alterations of bacterial
      communities as a result of MOS are likely to alter the functional capability of
      the cecum. 

PMID- 25769822
TI  - Using total internal reflection fluorescence microscopy to visualize rhodopsin
      containing cells.
AB  - Sunlight is captured and converted to chemical energy in illuminated
      environments. Although (bacterio)chlorophyll-based photosystems have been
      characterized in detail, retinal-based photosystems, rhodopsins, have only
      recently been identified as important mediators of light energy capture and
      conversion. Recent estimates suggest that up to 70% of cells in some environments
      harbor rhodopsins. However, because rhodopsin autofluorescence is low-comparable
      to that of carotenoids and significantly less than that of (bacterio)chlorophylls
      these estimates are based on metagenomic sequence data, not direct observation.
      We report here the use of ultrasensitive total internal reflection fluorescence
      (TIRF) microscopy to distinguish between unpigmented, carotenoid-producing, and
      rhodopsin-expressing bacteria. Escherichia coli cells were engineered to produce
      lycopene, beta-carotene, or retinal. A gene encoding an uncharacterized
      rhodopsin, actinorhodopsin, was cloned into retinal-producing E. coli. The
      production of correctly folded and membrane-incorporated actinorhodopsin was
      confirmed via development of pink color in E. coli and SDS-PAGE. Cells expressing
      carotenoids or actinorhodopsin were imaged by TIRF microscopy. The 561-nm
      excitation laser specifically illuminated rhodopsin-containing cells, allowing
      them to be differentiated from unpigmented and carotenoid-containing cells.
      Furthermore, water samples collected from the Delaware River were shown by PCR to
      have rhodopsin-containing organisms and were examined by TIRF microscopy.
      Individual microorganisms that fluoresced under illumination from the 561-nm
      laser were identified. These results verify the sensitivity of the TIRF
      microscopy method for visualizing and distinguishing between different molecules
      with low autofluorescence, making it useful for analyzing natural samples. 

PMID- 25769824
TI  - In Vivo Transmission of an IncA/C Plasmid in Escherichia coli Depends on
      Tetracycline Concentration, and Acquisition of the Plasmid Results in a Variable
      Cost of Fitness.
AB  - IncA/C plasmids are broad-host-range plasmids enabling multidrug resistance that
      have emerged worldwide among bacterial pathogens of humans and animals. Although
      antibiotic usage is suspected to be a driving force in the emergence of such
      strains, few studies have examined the impact of different types of antibiotic
      administration on the selection of plasmid-containing multidrug resistant
      isolates. In this study, chlortetracycline treatment at different concentrations
      in pig feed was examined for its impact on selection and dissemination of an
      IncA/C plasmid introduced orally via a commensal Escherichia coli host.
      Continuous low-dose administration of chlortetracycline at 50 g per ton had no
      observable impact on the proportions of IncA/C plasmid-containing E. coli from
      pig feces over the course of 35 days. In contrast, high-dose administration of
      chlortetracycline at 350 g per ton significantly increased IncA/C plasmid
      containing E. coli in pig feces (P < 0.001) and increased movement of the IncA/C
      plasmid to other indigenous E. coli hosts. There was no evidence of conjugal
      transfer of the IncA/C plasmid to bacterial species other than E. coli. In vitro
      competition assays demonstrated that bacterial host background substantially
      impacted the cost of IncA/C plasmid carriage in E. coli and Salmonella. In vitro
      transfer and selection experiments demonstrated that tetracycline at 32 MUg/ml
      was necessary to enhance IncA/C plasmid conjugative transfer, while subinhibitory
      concentrations of tetracycline in vitro strongly selected for IncA/C plasmid
      containing E. coli. Together, these experiments improve our knowledge on the
      impact of differing concentrations of tetracycline on the selection of IncA/C
      type plasmids. 

PMID- 25769825
TI  - Organic amendments to avocado crops induce suppressiveness and influence the
      composition and activity of soil microbial communities.
AB  - One of the main avocado diseases in southern Spain is white root rot caused by
      the fungus Rosellinia necatrix Prill. The use of organic soil amendments to
      enhance the suppressiveness of natural soil is an inviting approach that has
      successfully controlled other soilborne pathogens. This study tested the
      suppressive capacity of different organic amendments against R. necatrix and
      analyzed their effects on soil microbial communities and enzymatic activities.
      Two-year-old avocado trees were grown in soil treated with composted organic
      amendments and then used for inoculation assays. All of the organic treatments
      reduced disease development in comparison to unamended control soil, especially
      yard waste (YW) and almond shells (AS). The YW had a strong effect on microbial
      communities in bulk soil and produced larger population levels and diversity,
      higher hydrolytic activity and strong changes in the bacterial community
      composition of bulk soil, suggesting a mechanism of general suppression.
      Amendment with AS induced more subtle changes in bacterial community composition
      and specific enzymatic activities, with the strongest effects observed in the
      rhizosphere. Even if the effect was not strong, the changes caused by AS in bulk
      soil microbiota were related to the direct inhibition of R. necatrix by this
      amendment, most likely being connected to specific populations able to recolonize
      conducive soil after pasteurization. All of the organic amendments assayed in
      this study were able to suppress white root rot, although their suppressiveness
      appears to be mediated differentially. 

PMID- 25769826
TI  - Phosphate Limitation Induces Drastic Physiological Changes, Virulence-Related
      Gene Expression, and Secondary Metabolite Production in Pseudovibrio sp. Strain
      FO-BEG1.
AB  - Phosphorus is a vital nutrient for living organisms and is obtained by bacteria
      primarily via phosphate uptake. However, phosphate is often scarcely accessible
      in nature, and there is evidence that in many areas of the ocean, its
      concentration limits bacterial growth. Surprisingly, the phosphate starvation
      response has been extensively investigated in different model organisms (e.g.,
      Escherichia coli), but there is a dearth of studies on heterotrophic marine
      bacteria. In this work, we describe the response of Pseudovibrio sp. strain FO
      BEG1, a metabolically versatile alphaproteobacterium and potential symbiont of
      marine sponges, to phosphate limitation. We compared the physiology, protein
      expression, and secondary metabolite production under phosphate-limited
      conditions to those under phosphate surplus conditions. We observed that
      phosphate limitation had a pleiotropic effect on the physiology of the strain,
      triggering cell elongation, the accumulation of polyhydroxyalkanoate, the
      degradation of polyphosphate, and the exchange of membrane lipids in favor of
      phosphorus-free lipids such as sulfoquinovosyl diacylglycerols. Many proteins
      involved in the uptake and degradation of phospho-organic compounds were
      upregulated, together with subunits of the ABC transport system for phosphate.
      Under conditions of phosphate limitation, FO-BEG1 secreted compounds into the
      medium that conferred an intense yellow coloration to the cultures. Among these
      compounds, we identified the potent antibiotic tropodithietic acid. Finally,
      toxin-like proteins and other proteins likely involved in the interaction with
      the eukaryotic host were also upregulated. Altogether, our data suggest that
      phosphate limitation leads to a pronounced reorganization of FO-BEG1 physiology,
      involving phosphorus, carbon, and sulfur metabolism; cell morphology; secondary
      metabolite production; and the expression of virulence-related genes. 

PMID- 25769827
TI  - Taxonomic Identification of Ruminal Epithelial Bacterial Diversity during Rumen
      Development in Goats.
AB  - Understanding of the colonization process of epithelial bacteria attached to the
      rumen tissue during rumen development is very limited. Ruminal epithelial
      bacterial colonization is of great significance for the relationship between the
      microbiota and the host and can influence the early development and health of the
      host. MiSeq sequencing of 16S rRNA genes and quantitative real-time PCR (qPCR)
      were applied to characterize ruminal epithelial bacterial diversity during rumen
      development in this study. Seventeen goat kids were selected to reflect the no
      rumination (0 and 7 days), transition (28 and 42 days), and rumination (70 days)
      phases of animal development. Alpha diversity indices (operational taxonomic unit
      [OTU] numbers, Chao estimate, and Shannon index) increased (P < 0.01) with age,
      and principal coordinate analysis (PCoA) revealed that the samples clustered
      together according to age group. Phylogenetic analysis revealed that
      Proteobacteria, Firmicutes, and Bacteroidetes were detected as the dominant phyla
      regardless of the age group, and the abundance of Proteobacteria declined
      quadratically with age (P < 0.001), while the abundances of Bacteroidetes (P =
      0.088) and Firmicutes (P = 0.009) increased with age. At the genus level,
      Escherichia (80.79%) dominated at day zero, while Prevotella, Butyrivibrio, and
      Campylobacter surged (linearly; P < 0.01) in abundance at 42 and 70 days. qPCR
      showed that the total copy number of epithelial bacteria increased linearly (P =
      0.013) with age. In addition, the abundances of the genera Butyrivibrio,
      Campylobacter, and Desulfobulbus were positively correlated with rumen weight,
      rumen papilla length, ruminal ammonia and total volatile fatty acid
      concentrations, and activities of carboxymethylcellulase (CMCase) and xylanase.
      Taking the data together, colonization by ruminal epithelial bacteria is age
      related (achieved at 2 months) and might participate in the anatomic and
      functional development of the rumen. 

PMID- 25769828
TI  - Nitrite Control over Dissimilatory Nitrate/Nitrite Reduction Pathways in
      Shewanella loihica Strain PV-4.
AB  - Shewanella loihica strain PV-4 harbors both a functional denitrification (NO3 (-)
      >N2) and a respiratory ammonification (NO3 (-)->NH4 (+)) pathway. Batch and
      chemostat experiments revealed that NO2 (-) affects pathway selection and the
      formation of reduced products. Strain PV-4 cells grown with NO2 (-) as the sole
      electron acceptor produced exclusively NH4 (+). With NO3 (-) as the electron
      acceptor, denitrification predominated and N2O accounted for ~90% of reduced
      products in the presence of acetylene. Chemostat experiments demonstrated that
      the NO2 (-):NO3 (-) ratio affected the distribution of reduced products, and
      respiratory ammonification dominated at high NO2 (-):NO3 (-) ratios, whereas low
      NO2 (-):NO3 (-) ratios favored denitrification. The NO2 (-):NO3 (-) ratios
      affected nirK transcript abundance, a measure of denitrification activity, in the
      chemostat experiments, and cells grown at a NO2 (-):NO3 (-) ratio of 3 had ~37
      fold fewer nirK transcripts per cell than cells grown with NO3 (-) as the sole
      electron acceptor. In contrast, the transcription of nrfA, implicated in NO2 (-)
      to-NH4 (+) reduction, remained statistically unchanged under continuous
      cultivation conditions at NO2 (-):NO3 (-) ratios below 3. At NO2 (-):NO3 (-)
      ratios above 3, both nirK and nrfA transcript numbers decreased and the chemostat
      culture washed out, presumably due to NO2 (-) toxicity. These findings implicate
      NO2 (-) as a relevant modulator of NO3 (-) fate in S. loihica strain PV-4, and,
      by extension, suggest that NO2 (-) is a relevant determinant for N retention
      (i.e., ammonification) versus N loss and greenhouse gas emission (i.e.,
      denitrification). 

PMID- 25769829
TI  - Genes Indicative of Zoonotic and Swine Pathogens Are Persistent in Stream Water
      and Sediment following a Swine Manure Spill.
AB  - Manure spills into streams are relatively frequent, but no studies have
      characterized stream contamination with zoonotic and veterinary pathogens, or
      fecal chemicals, following a spill. We tested stream water and sediment over 25
      days and downstream for 7.6 km for the following: fecal indicator bacteria (FIB),
      the fecal indicator chemicals cholesterol and coprostanol, 20 genes for zoonotic
      and swine-specific bacterial pathogens by presence/absence PCR for viable cells,
      one swine-specific Escherichia coli toxin gene (STII gene) by quantitative PCR
      (qPCR), and nine human and animal viruses by qPCR or reverse transcription-qPCR.
      Twelve days postspill, and 4.2 km downstream, water concentrations of FIB,
      cholesterol, and coprostanol were 1 to 2 orders of magnitude greater than those
      detected before, or above, the spill, and genes indicating viable zoonotic or
      swine-infectious Escherichia coli were detected in water or sediment. STII gene
      levels increased from undetectable before or above the spill to 10(5) copies/100
      ml of water 12 days postspill. Thirteen of 14 water (8/9 sediment) samples had
      viable STII-carrying cells postspill. Eighteen days postspill, porcine adenovirus
      and teschovirus were detected 5.6 km downstream. FIB concentrations (per gram
      [wet weight]) in sediment were greater than in water, and sediment was a
      continuous reservoir of genes and chemicals postspill. Constituent concentrations
      were much lower, and detections less frequent, in a runoff event (200 days
      postspill) following manure application, although the swine-associated STII and
      stx2e genes were detected. Manure spills are an underappreciated pathway for
      livestock-derived contaminants to enter streams, with persistent environmental
      outcomes and the potential for human and veterinary health consequences. 

PMID- 25769830
TI  - Pseudomycoicidin, a Class II Lantibiotic from Bacillus pseudomycoides.
AB  - Lantibiotics are ribosomally synthesized antimicrobial peptides with substantial
      posttranslational modifications. They are characterized by the unique amino acids
      lanthionine and methyllanthionine, which are introduced by dehydration of Ser/Thr
      residues and linkage of the resulting dehydrated amino acids with Cys residues.
      BLAST searches using the mersacidin biosynthetic enzyme (MrsM) in the NCBI
      database revealed a new class II lantibiotic gene cluster in Bacillus
      pseudomycoides DSM 12442. Production of an antimicrobial substance with activity
      against Gram-positive bacteria was detectable in a cell wash extract of this
      strain. The substance was partially purified, and mass spectrometric analysis
      predicted a peptide of 2,786 Da in the active fraction. In order to characterize
      the putative lantibiotic further, heterologous expression of the predicted
      biosynthetic genes was performed in Escherichia coli. Coexpression of the
      prepeptide (PseA) along with the corresponding modification enzyme (PseM)
      resulted in the production of a modified peptide with the corresponding mass,
      carrying four out of eight possible dehydrations and supporting the presence of
      four thioether and one disulfide bridge. After the proteolytic removal of the
      leader, the core peptide exhibited antimicrobial activity. In conclusion,
      pseudomycoicidin is a novel lantibiotic with antimicrobial activity that was
      heterologously produced in E. coli. 

PMID- 25769831
TI  - Evidence of active methanogen communities in shallow sediments of the sonora
      margin cold seeps.
AB  - In the Sonora Margin cold seep ecosystems (Gulf of California), sediments
      underlying microbial mats harbor high biogenic methane concentrations, fueling
      various microbial communities, such as abundant lineages of anaerobic
      methanotrophs (ANME). However, the biodiversity, distribution, and metabolism of
      the microorganisms producing this methane remain poorly understood. In this
      study, measurements of methanogenesis using radiolabeled dimethylamine,
      bicarbonate, and acetate showed that biogenic methane production in these
      sediments was mainly dominated by methylotrophic methanogenesis, while the
      proportion of autotrophic methanogenesis increased with depth. Congruently,
      methane production and methanogenic Archaea were detected in culture enrichments
      amended with trimethylamine and bicarbonate. Analyses of denaturing gradient gel
      electrophoresis (DGGE) fingerprinting and reverse-transcribed PCR-amplified 16S
      rRNA sequences retrieved from these enrichments revealed the presence of active
      methylotrophic Methanococcoides burtonii relatives and several new autotrophic
      Methanogenium lineages, confirming the cooccurrence of Methanosarcinales and
      Methanomicrobiales methanogens with abundant ANME populations in the sediments of
      the Sonora Margin cold seeps. 

PMID- 25769832
TI  - Site history and edaphic features override the influence of plant species on
      microbial communities in restored tidal freshwater wetlands.
AB  - Restored wetland soils differ significantly in physical and chemical properties
      from their natural counterparts even when plant community compositions are
      similar, but effects of restoration on microbial community composition and
      function are not well understood. Here, we investigate plant-microbe
      relationships in restored and natural tidal freshwater wetlands from two
      subestuaries of the Chesapeake Bay. Soil samples were collected from the root
      zone of Typha latifolia, Phragmites australis, Peltandra virginica, and Lythrum
      salicaria. Soil microbial composition was assessed using 454 pyrosequencing, and
      genes representing bacteria, archaea, denitrification, methanogenesis, and
      methane oxidation were quantified. Our analysis revealed variation in some
      functional gene copy numbers between plant species within sites, but intersite
      comparisons did not reveal consistent plant-microbe trends. We observed more
      microbial variations between plant species in natural wetlands, where plants have
      been established for a long period of time. In the largest natural wetland site,
      sequences putatively matching methanogens accounted for ~17% of all sequences,
      and the same wetland had the highest numbers of genes coding for methane coenzyme
      A reductase (mcrA). Sequences putatively matching aerobic methanotrophic bacteria
      and anaerobic methane-oxidizing archaea (ANME) were detected in all sites,
      suggesting that both aerobic and anaerobic methane oxidation are possible in
      these systems. Our data suggest that site history and edaphic features override
      the influence of plant species on microbial communities in restored wetlands. 

PMID- 25769833
TI  - Integrated cryptosporidium assay to determine oocyst density, infectivity, and
      genotype for risk assessment of source and reuse water.
AB  - Cryptosporidium continues to be problematic for the water industry, with risk
      assessments often indicating that treatment barriers may fail under extreme
      conditions. However, risk analyses have historically used oocyst densities and
      not considered either oocyst infectivity or species/genotype, which can result in
      an overestimation of risk if the oocysts are not human infective. We describe an
      integrated assay for determining oocyst density, infectivity, and genotype from a
      single-sample concentrate, an important advance that overcomes the need for
      processing multiple-grab samples or splitting sample concentrates for separate
      analyses. The assay incorporates an oocyst recovery control and is compatible
      with standard primary concentration techniques. Oocysts were purified from
      primary concentrates using immunomagnetic separation prior to processing by an
      infectivity assay. Plate-based cell culture was used to detect infectious foci,
      with a monolayer washing protocol developed to allow recovery and enumeration of
      oocysts. A simple DNA extraction protocol was developed to allow typing of any
      wells containing infectious Cryptosporidium. Water samples from a variety of
      source water and wastewater matrices, including a semirural catchment,
      wastewater, an aquifer recharge site, and storm water, were analyzed using the
      assay. Results demonstrate that the assay can reliably determine oocyst
      densities, infectivity, and genotype from single-grab samples for a variety of
      water matrices and emphasize the varying nature of Cryptosporidium risk extant
      throughout source waters and wastewaters. This assay should therefore enable a
      more comprehensive understanding of Cryptosporidium risk for different water
      sources, assisting in the selection of appropriate risk mitigation measures. 

PMID- 25769834
TI  - Sharing a Host Plant (Wheat [Triticum aestivum]) Increases the Fitness of
      Fusarium graminearum and the Severity of Fusarium Head Blight but Reduces the
      Fitness of Grain Aphids (Sitobion avenae).
AB  - We hypothesized that interactions between fusarium head blight-causing pathogens
      and herbivores are likely to occur because they share wheat as a host plant. Our
      aim was to investigate the interactions between the grain aphid, Sitobion avenae,
      and Fusarium graminearum on wheat ears and the role that host volatile chemicals
      play in mediating interactions. Wheat ears were treated with aphids and F.
      graminearum inoculum, together or separately, and disease progress was monitored
      by visual assessment and by quantification of pathogen DNA and mycotoxins. Plants
      exposed to both aphids and F. graminearum inoculum showed accelerated disease
      progression, with a 2-fold increase in disease severity and 5-fold increase in
      mycotoxin accumulation over those of plants treated only with F. graminearum.
      Furthermore, the longer the period of aphid colonization of the host prior to
      inoculation with F. graminearum, the greater the amount of pathogen DNA that
      accumulated. Headspace samples of plant volatiles were collected for use in aphid
      olfactometer assays and were analyzed by gas chromatography-mass spectrometry (GC
      MS) and GC-coupled electroantennography. Disease-induced plant volatiles were
      repellent to aphids, and 2-pentadecanone was the key semiochemical underpinning
      the repellent effect. We measured aphid survival and fecundity on infected wheat
      ears and found that both were markedly reduced on infected ears. Thus,
      interactions between F. graminearum and grain aphids on wheat ears benefit the
      pathogen at the expense of the pest. Our findings have important consequences for
      disease epidemiology, because we show increased spread and development of host
      disease, together with greater disease severity and greater accumulation of
      pathogen DNA and mycotoxin, when aphids are present. 

PMID- 25769835
TI  - Tropical strains of Ralstonia solanacearum Outcompete race 3 biovar 2 strains at
      lowland tropical temperatures.
AB  - Bacterial wilt, caused by members of the heterogenous Ralstonia solanacearum
      species complex, is an economically important vascular disease affecting many
      crops. Human activity has widely disseminated R. solanacearum strains, increasing
      their global agricultural impact. However, tropical highland race 3 biovar 2
      (R3bv2) strains do not cause disease in tropical lowlands, even though they are
      virulent at warm temperatures. We tested the hypothesis that differences in
      temperature adaptation and competitive fitness explain the uneven geographic
      distribution of R. solanacearum strains. Using three phylogenetically and
      ecologically distinct strains, we measured competitive fitness at two
      temperatures following paired-strain inoculations of their shared host, tomato.
      Lowland tropical strain GMI1000 was only weakly virulent on tomato under
      temperate conditions (24 degrees C for day and 19 degrees C for night [24/19
      degrees C]), but highland tropical R3bv2 strain UW551 and U.S. warm temperate
      strain K60 were highly virulent at both 24/19 degrees C and 28 degrees C. Strain
      K60 was significantly more competitive than both GMI1000 and UW551 in tomato
      rhizospheres and stems at 28 degrees C, and GMI1000 also outcompeted UW551 at 28
      degrees C. The results were reversed at cooler temperatures, at which highland
      strain UW551 generally outcompeted GMI1000 and K60 in planta. The superior
      competitive index of UW551 at 24/19 degrees C suggests that adaptation to cool
      temperatures could explain why only R3bv2 strains threaten highland agriculture.
      Strains K60 and GMI1000 each produced different bacteriocins that inhibited
      growth of UW551 in culture. Such interstrain inhibition could explain why R3bv2
      strains do not cause disease in tropical lowlands. 

PMID- 25769836
TI  - Species richness and adaptation of marine fungi from deep-subseafloor sediments.
AB  - The fungal kingdom is replete with unique adaptive capacities that allow fungi to
      colonize a wide variety of habitats, ranging from marine habitats to freshwater
      and terrestrial habitats. The diversity, importance, and ecological roles of
      marine fungi have recently been highlighted in deep-subsurface sediments using
      molecular methods. Fungi in the deep-marine subsurface may be specifically
      adapted to life in the deep biosphere, but this can be demonstrated only using
      culture-based analyses. In this study, we investigated culturable fungal
      communities from a record-depth sediment core sampled from the Canterbury Basin
      (New Zealand) with the aim to reveal endemic or ubiquist adapted isolates playing
      a significant ecological role(s). About 200 filamentous fungi (68%) and yeasts
      (32%) were isolated. Fungal isolates were affiliated with the phyla Ascomycota
      and Basidiomycota, including 21 genera. Screening for genes involved in secondary
      metabolite synthesis also revealed their bioactive compound synthesis potential.
      Our results provide evidence that deep-subsurface fungal communities are able to
      survive, adapt, grow, and interact with other microbial communities and highlight
      that the deep-sediment habitat is another ecological niche for fungi. 

PMID- 25769837
TI  - Processing Environment and Ingredients Are Both Sources of Leuconostoc gelidum,
      Which Emerges as a Major Spoiler in Ready-To-Eat Meals.
AB  - Mesophilic and psychrotrophic organism viable counts, as well as high-throughput
      16S rRNA gene-based pyrosequencing, were performed with the aim of elucidating
      the origin of psychrotrophic lactic acid bacteria (LAB) in a ready-to-eat (RTE)
      meal manufacturing plant. The microbial counts of the products at the end of the
      shelf life were greatly underestimated when mesophilic incubation was implemented
      due to overlooked, psychrotrophic members of the LAB. Pseudomonas spp.,
      Enterobacteriaceae, Streptococcaceae, and Lactobacillus spp. constituted the most
      widespread operational taxonomic units (OTUs), whereas Leuconostoc gelidum was
      detected as a minor member of the indigenous microbiota of the food ingredients
      and microbial community of the processing environment, albeit it colonized
      samples at almost every sampling point on the premises. However, L. gelidum
      became the most predominant microbe at the end of the shelf life. The ability of
      L. gelidum to outgrow notorious, spoilage-related taxa like Pseudomonas,
      Brochothrix, and Lactobacillus underpins its high growth dynamics and severe
      spoilage character under refrigeration temperatures. The use of predicted
      metagenomes was useful for observation of putative gene repertoires in the
      samples analyzed in this study. The end products grouped in clusters
      characterized by gene profiles related to carbohydrate depletion presumably
      associated with a fast energy yield, a finding which is consistent with the
      fastidious nature of highly competitive LAB that dominated at the end of the
      shelf life. The present study showcases the detrimental impact of contamination
      with psychrotrophic LAB on the shelf life of packaged and cold-stored foodstuffs
      and the long-term quality implications for production batches once resident
      microbiota are established in the processing environment. 

PMID- 25769838
TI  - Efficient Production of 2,5-Diketo-d-Gluconate via Heterologous Expression of 2
      Ketogluconate Dehydrogenase in Gluconobacter japonicus.
AB  - 2,5-Diketo-d-gluconate (2,5DKG) is a compound that can be the intermediate for d
      tartrate and also vitamin C production. Although Gluconobacter oxydans NBRC3293
      produces 2,5DKG from d-glucose via d-gluconate and 2-keto-d-gluconate (2KG), with
      accumulation of the product in the culture medium, the efficiency of 2,5DKG
      production is unsatisfactory because there is a large amount of residual d
      gluconate at the end of the biotransformation process. Oxidation of 2KG to 2,5DKG
      is catalyzed by a membrane-bound flavoprotein-cytochrome c complex: 2-keto
      gluconate dehydrogenase (2KGDH). Here, we studied the kgdSLC genes encoding 2KGDH
      in G. oxydans NBRC3293 to improve 2,5DKG production by Gluconobacter spp. The
      kgdS, kgdL, and kgdC genes correspond to the small, large, and cytochrome
      subunits of 2KGDH, respectively. The kgdSLC genes were cloned into a broad-host
      range vector carrying a DNA fragment of the putative promoter region of the
      membrane-bound alcohol dehydrogenase gene of G. oxydans for expression in
      Gluconobacter spp. According to our results, 2KGDH that was purified from the
      recombinant Gluconobacter cells showed characteristics nearly the same as those
      reported previously. We also expressed the kgdSLC genes in a mutant strain of
      Gluconobacter japonicus NBRC3271 (formerly Gluconobacter dioxyacetonicus IFO3271)
      engineered to produce 2KG efficiently from a mixture of d-glucose and d
      gluconate. This mutant strain consumed almost all of the starting materials (d
      glucose and d-gluconate) to produce 2,5DKG quantitatively as a seemingly unique
      metabolite. To our knowledge, this is the first report of a Gluconobacter strain
      that produces 2,5DKG efficiently and homogeneously. 

PMID- 25769839
TI  - An evaluation of the lower extremity muscle strength of patients with chronic
      venous insufficiency.
AB  - OBJECTIVE: In this study, the aim was to evaluate the lower extremity muscle
      strength in patients with chronic venous insufficiency using an isokinetic
      dynamometer. METHODS: The study comprised a group of 36 lower extremities of 23
      patients diagnosed with chronic venous insufficiency and a control group of 40
      lower extremities of 20 patients who did not have chronic venous insufficiency.
      In the diagnosis and evaluation of chronic venous insufficiency,
      photoplethysmography was used to evaluate the venous return circulation time.
      Visual Analog Scale scoring was applied to define the level of pain of the
      patients. Muscle strength measurements were made in all the lower extremities by
      using an isokinetic dynamometer. RESULTS: A statistically significant difference
      was detected between the groups in terms of the muscle strength parameters in the
      ankle plantar flexion, and knee flexor and extensor muscles. However, no
      statistically significant difference was found between the groups in the ankle
      dorsiflexion muscle strength parameters. A significant difference was determined
      in the ratio of ankle dorsiflexion/plantar flexion muscle strength between the
      mild, moderate and severe venous insufficiency groups. A statistically
      considerable negative correlation was found between the Visual Analog Scale
      scores and the photoplethysmography results. According to the Visual Analog Scale
      results, as the degree of venous insufficiency increased, so did the level of
      pain. CONCLUSION: Impaired lower extremity muscle strength was observed in
      chronic venous insufficiency patients. Although the current study was consistent
      with literature in respect of impaired calf muscle strength, this finding was
      also seen in the thigh muscles. Furthermore, we concluded that if venous
      insufficiency becomes more severe, impaired calf muscle strength becomes more
      evident.

PMID- 25769840
TI  - First drug is approved under scheme that gives patients access to unlicensed
      medicines.

PMID- 25769841
TI  - Experimental evidence for curcumin and its analogs for management of diabetes
      mellitus and its associated complications.
AB  - Diabetes mellitus is a serious world health problem and one of the most studied
      diseases; a major concern about its treatment is that beta-cell mass and
      functionality is hard to restore. In addition, it is frequently associated with
      severe complications, such as diabetic nephropathy and cardiomyopathy. The anti
      inflammatory, anti-oxidative and anti-apoptotic properties of curcumin have made
      it a promising molecule for the treatment of this pathology; however, its
      solubility and bioavailability problems are still the subject of multiple
      studies. To cope with those difficulties, several approaches have been evaluated,
      such as the development of pharmaceutical formulations and curcumin analogs. This
      review discusses some of the studied therapeutic targets for curcumin in diabetes
      as well as the structural characteristics and targets of its analogs. The
      shortening of the central seven-carbon chain of curcumin has given rise to
      compounds without glucose-lowering effects but potentially useful for the
      treatment of diabetes complications; whereas preserving this chain retains the
      glucose-lowering properties. Most of the analogs discussed here have been
      recently synthesized and tested in animal models of type 1 diabetes; more studies
      in models of type 2 diabetes are needed.

PMID- 25769842
TI  - Venlafaxine increases cell proliferation and regulates DISC1, PDE4B and NMDA
      receptor 2B expression in the hippocampus in chronic mild stress mice.
AB  - Recent evidence has identified disrupted in schizophrenia-1 (DISC1) as an
      important genetic risk factor for the development of many psychiatric disorders,
      including major depressive disorders. In addition, studies using animal models
      have demonstrated that chronic stress affects hippocampal structure and function.
      However, the functional effects of chronic stress on DISC1 remain unknown. Using
      a chronic mild stress (CMS) paradigm, we investigated the effects of CMS on
      depressive-like behaviors, hippocampal cell proliferation, and hippocampal
      protein expression of DISC1, phosphodiesterase 4B (PDE4B) and N-methyl-d
      aspartate receptor 2B subunit (NMDA receptor 2B), which may be involved in the
      regulation of DISC1 and neurogenesis. We also examined the effects and possible
      mechanisms of the antidepressant venlafaxine in CMS mice. CMS increased the
      expression of DISC1 and PDE4B. Chronic treatment with venlafaxine blocked the
      increases in these proteins, and also reversed the CMS-induced decrease in
      neurogenesis and NMDA receptor 2B protein in the hippocampus. These results
      suggest that DISC1 may play an important role in the etiology of depression and
      in the action of antidepressants.

PMID- 25769843
TI  - Evolution of cadmium effects in the testis and sperm of the tropical fish
      Gymnotus carapo.
AB  - The present study investigated the testis and sperm morphology of the tropical
      fish Gymnotus carapo after exposure to increasing CdCl2 concentrations (5-40 MUM)
      for 24 and 96 h. The treatments induced Cd accumulation in the testis and a
      decrease in the gonadosomatic index from a 10 MUM. Cd induced alterations in
      testis since 24h; however the extension and severity of damages increased after
      96 h in all tested concentrations. Marked variations in the cysts size,
      proliferation of the interstitial tissue, infiltration of inflammatory cells,
      necrosis, reduction of germ cells and sperm aggregation was observed in 96 h
      treated fishes. In this time, there was a complete absence of germ cells in the
      testis of fish treated with 40 MUM. The ultrastructural analysis allowed for the
      visualization of the initial damages over germ cells, such as the presence of
      vacuoles in the cytoplasm of spermatogonia, spermatocytes, and spermatids.
      Exposed fish (20 MUM for 24 and 96 h) had alterations in sperm number and
      morphology. These results are important for establishing a direct correlation
      between the Cd accumulation and incidence of damages and can help characterize
      the mechanism of Cd-induced pathogenesis in the male reproductive system.

PMID- 25769844
TI  - Significance of accurate statistical analysis of experimental studies using
      laboratory animal models.

PMID- 25769845
TI  - Evaluation of the platelet-to-lymphocyte ratio as a prognostic indicator in a
      European cohort of patients with prostate cancer treated with radiotherapy.
AB  - OBJECTIVES: Recent evidence suggests that the presence of a systemic inflammatory
      response plays an important role in the progression of several solid tumors. The
      platelet-to-lymphocyte ratio (PLR) has been proposed as an easily assessable
      marker of systemic inflammation and has been shown to represent a prognostic
      marker in different cancer entities. To evaluate the prognostic value of the PLR
      in prostate cancer, we performed the present study. METHODS AND MATERIALS: Data
      from 374 consecutive patients with prostate cancer, treated with 3D conformal
      radiotherapy from 1999 to 2007, were analyzed. Distant metastases-free survival
      (MFS), cancer-specific survival (CSS), overall survival (OS), biochemical disease
      free survival, and time to salvage systemic therapy were assessed using the
      Kaplan-Meier method. Cox proportional hazards analysis was performed to calculate
      hazard ratio (HR) and 95% CI. Multivariate Cox regression analysis was performed
      to adjust for other covariates. RESULTS: Using receiver operating characteristics
      analysis, the optimal cutoff level for the PLR was 190. Kaplan-Meier analyses
      revealed that PLR>=190 was a prognostic factor for decreased MFS (P = 0.004), CSS
      (P = 0.004), and OS (P = 0.024) whereas a significant association of an elevated
      PLR with biochemical disease-free survival (P = 0.740) and time to salvage
      systemic therapy (P = 0.063) was not detected. In multivariate analysis, an
      increased PLR remained a significant prognostic factor for poor MFS (HR = 2.24,
      95% CI: 1.06-4.76, P = 0.036), CSS (HR = 3.99, 95% CI: 1.19-13.4, P = 0.025), and
      OS (HR = 1.87, 95% CI: 1.02-3.42, P = 0.044). CONCLUSIONS: Our findings indicate
      that the PLR may predict prognosis in patients with prostate cancer and may
      contribute to future individual risk assessment in them.

PMID- 25769846
TI  - Peripheral vascular leakage in uveitis: clinical and angiographic findings.

PMID- 25769847
TI  - Corneal thickness profile and posterior corneal astigmatism in normal corneas.
AB  - PURPOSE: To analyze the influence of corneal thickness profile on posterior
      corneal astigmatism (PA). DESIGN: Prospective, observational study. SUBJECTS: We
      included 418 normal subjects (213 men and 205 women) ranging in age from 6 to 93
      years (49.0 +/- 23.4 years, mean +/- standard deviation) in this study. METHODS:
      Anterior and posterior corneal topography were evaluated using 3-dimensional
      anterior segment optical coherence tomography. Pericentral corneal thickness
      (PCT) in each quadrant (superior, inferior, nasal, and temporal) was measured,
      and average PCT in the vertical (superior + inferior) and horizontal (nasal +
      temporal) directions was calculated. Posterior corneal astigmatism was calculated
      as (1) assumed PA based on the anterior corneal curvature measurement and the
      keratometric index and (2) actual PA derived from the direct measurement of
      posterior corneal curvature. MAIN OUTCOME MEASURES: Corneal thickness
      distribution and the difference between assumed and actual PA. RESULTS: The PCT
      was significantly greater in the vertical (546.0 +/- 31.8 MUm) than in the
      horizontal direction (542.6 +/- 31.7 MUm) (P < 0.0001), and the difference
      between them was significantly correlated with subject age (r = 0.518, P <
      0.0001). The difference between assumed and actual PA significantly correlated
      with the discrepancy between vertical and horizontal PCT (r = 0.819, P < 0.0001),
      as well as subject age (r = 0.533, P < 0.0001). CONCLUSIONS: Corneal thickness is
      greater in the vertical than in the horizontal direction, making the PA more
      against-the-rule pattern than calculated on the basis of the anterior corneal
      curvature measurement only. Such discrepancy is more prominent in older patients.

PMID- 25769848
TI  - Gender and venture capital decision-making: the effects of technical background
      and social capital on entrepreneurial evaluations.
AB  - Research on gender and workplace decision-making tends to address either supply
      side disparities between men's and women's human and social capital, or demand
      side differences in the status expectations of women and men workers. In
      addition, this work often relies on causal inferences drawn from empirical data
      collected on worker characteristics and their workplace outcomes. In this study,
      we demonstrate how tangible education and work history credentials - typically
      associated with supply-side characteristics - work in tandem with cultural
      beliefs about gender to influence the evaluative process that underlies venture
      capital decisions made in high-growth, high-tech entrepreneurship. Using an
      experimental design, we simulate funding decisions by venture capitalists (VCs)
      for men and women entrepreneurs that differ in technical background and the
      presence of important social ties. We demonstrate the presence of two distinct
      aspects of VCs' evaluation: that of the venture and that of the entrepreneur, and
      find that the gender of the entrepreneur influences evaluations most when the
      person, rather than the venture, is the target of evaluation. Technical
      background qualifications moderate the influence of gendered expectations, and
      women receive more of a payoff than men from having a close contact to the
      evaluating VC. We discuss the implications for future research on gender and
      work. 

PMID- 25769849
TI  - Religiosity and reactions to terrorism.
AB  - Although many of the world's most serious outbreaks of conflict and violence
      center on religion, social science research has had relatively little to say
      about religion's unique role in shaping individuals' attitudes about these
      events. In this paper we investigate whether Americans' religious beliefs play a
      central role in shaping attitudes toward the continuing threat of terrorism and
      their willingness to assist officials in countering these perceived threats. Our
      analysis of an original data collection of almost 1600 Americans shows that more
      religious respondents are more likely to express concerns about terrorism.
      However, this relationship is mediated by their level of conservatism. We also
      find that more religious respondents are more likely to claim that they will
      assist government officials in countering terrorism. This relationship remained
      even after accounting for conservatism, and people's general willingness to help
      police solve crimes like breaking and entering. 

PMID- 25769850
TI  - School choice & social stratification: how intra-district transfers shift the
      racial/ethnic and economic composition of schools.
AB  - The liberation model hypothesizes that school choice liberates students from
      underperforming schools by giving them the opportunity to seek academically
      superior schooling options outside of their neighborhoods. Subsequently, school
      choice is hypothesized to diminish stratification in schools. Data from one urban
      school district is analyzed to test these hypotheses. We specifically examine
      which factors influence the propensity for parents to participate in choice, and
      how school choice changes the racial/ethnic and economic composition of schools.
      We further examine how school choice influences similar changes within distinct
      sociogeographic areas within the district. We find that families who are zoned to
      more racially/ethnically and economically diverse schools in sociogeographically
      diverse areas are more likely to participate in school choice. We also find that
      intra-district choice is associated with a slight increase in social
      stratification throughout the district, with more substantial stratification
      occurring in the most demographically diverse areas and schools. 

PMID- 25769851
TI  - Gender, justice and work: a distributive approach to perceptions of housework
      fairness.
AB  - Most women and men report that the division of domestic labor in their household
      is fair, despite women undertaking approximately seventy percent of housework.
      This raises questions about how fairness is evaluated within partnerships. We
      explore how parenthood and relationship transitions affect perceptions of
      housework fairness using panel data from the Household, Income and Labour
      Dynamics in Australia Survey and panel regression models. Our results indicate
      that net of actual housework divisions, socio-demographic factors, time
      availability and relative resources, the transition to parenthood increases
      women's perceptions of housework fairness immediately following the birth of a
      child, but decreases them in the long run. Relationship transitions have no
      independent effects. Our findings suggest that parenthood transitions are
      associated with changes in women's identity, cognitive evaluations of fairness
      and feelings of entitlement, as indicated by distributive justice theory. 

PMID- 25769852
TI  - Privacy, technology, and norms: the case of Smart Meters.
AB  - Norms shift and emerge in response to technological innovation. One such
      innovation is Smart Meters - components of Smart Grid energy systems capable of
      minute-to-minute transmission of consumer electricity use information. We
      integrate theory from sociological research on social norms and privacy to
      examine how privacy threats affect the demand for and expectations of norms that
      emerge in response to new technologies, using Smart Meters as a test case.
      Results from three vignette experiments suggest that increased threats to privacy
      created by Smart Meters are likely to provoke strong demand for and expectations
      of norms opposing the technology and that the strength of these normative rules
      is at least partly conditional on the context. Privacy concerns vary little with
      actors' demographic characteristics. These findings contribute to theoretical
      understanding of norm emergence and have practical implications for implementing
      privacy protections that effectively address concerns of electricity users. 

PMID- 25769853
TI  - Diverging fortunes? Economic well-being of Latinos and African Americans in new
      rural destinations.
AB  - The geographic diffusion of Latinos from immigrant gateways to newly-emerging
      rural destinations is one of the most significant recent trends in U.S.
      population redistribution. Yet, few studies have explored how Latinos have fared
      in new destinations, and even fewer have examined economic implications for other
      minority workers and their families. We use county-level data from the 1990 and
      2000 U.S. Census and the 2006-2010 American Community Survey to compare the
      changing economic circumstances (e.g., employment and unemployment, poverty,
      income, and homeownership) of Latinos and African Americans in new Latino
      boomtowns. We also evaluate the comparative economic trajectories of Latinos in
      new destinations and established gateways. During the 1990s, new rural
      destinations provided clear economic benefits to Latinos, even surpassing African
      Americans on some economic indicators. The 2000s, however, ushered in higher
      rates of Latino poverty; the economic circumstances of Latinos also deteriorated
      more rapidly in new vis-a-vis traditional destinations. By 2010, individual and
      family poverty rates in new destinations were significantly higher among Latinos
      than African Americans, despite higher labor force participation and lower levels
      of unemployment. Difference-in-difference models demonstrate that in both the
      1990s and 2000s, economic trajectories of African Americans in new Latino
      destinations largely mirrored those observed in places without large Latino
      influxes. Any economic benefits for Latinos in new rural destinations thus have
      not come at the expense of African Americans. 

PMID- 25769854
TI  - Employers' social contacts and their hiring behavior in a factorial survey.
AB  - We investigate whether referrals from employers' business and professional
      contacts matter in the hiring process. Additionally, we examine whether the
      effect of referrals varies depending on: (1) the signaling role of education
      during the hiring process, and (2) applicants' level of education. Based on a
      combination of a factorial survey and an experimental design with a sample of
      English employers, we measure the effect of referrals on employers' hiring
      assessments. We find only weak evidence that referred applicants are considered
      more trainable than otherwise identical applicants that do not have a tie with
      the employer. More detailed analyses show that referrals do matter for employers
      who consider education a noisy signal, in line with the argument that informal
      recruitment can represent a strategy for employers to compensate for poor
      signaling. Referrals are especially beneficial for highly educated applicants,
      probably because employers need some guarantee against possible wage or turnover
      costs. 

PMID- 25769855
TI  - The socioeconomic consequences of dropping out of high school: evidence from an
      analysis of siblings.
AB  - There is widespread belief that dropping out of high school leads to economic
      hardship. This belief rests on tenuous evidence. High school dropouts likely face
      an increased risk of economic hardship because of differences beyond a high
      school diploma. In particular, dropouts are more likely to come from
      disadvantaged backgrounds and thus face an elevated risk of economic hardship.
      Using data from the National Longitudinal Study of Youth 1979 Cohort, I estimate
      the consequences of dropping out by comparing dropouts to their siblings who
      completed high school. I also present OLS regression estimates using the same
      data. OLS regression estimates are consistently higher than sibling fixed effects
      estimates with the largest discrepancy occurring between estimates of the effect
      of dropping out on income-to-poverty ratio. However, the sibling fixed effect
      estimates reveal that dropping out has an effect on economic hardship net of
      unobserved background characteristics that are shared by siblings. I conclude
      with a discussion of how recent policy shifts affect the economic standing of low
      ability students and suggest avenues for future research. 

PMID- 25769856
TI  - Developing spatial inequalities in carbon appropriation: a sociological analysis
      of changing local emissions across the United States.
AB  - This study examines an overlooked dynamic in sociological research on greenhouse
      gas emissions: how local areas appropriate the global carbon cycle for use and
      exchange purposes as they develop. Drawing on theories of place and space, we
      hypothesize that development differentially drives and spatially decouples use-
      and exchange-oriented emissions at the local level. To test our hypotheses, we
      integrate longitudinal, county-level data on residential and industrial emissions
      from the Vulcan Project with demographic, economic and environmental data from
      the U.S. Census Bureau and National Land Change Database. Results from spatial
      regression models with two-way fixed-effects indicate that alongside innovations
      and efficiencies capable of reducing environmentally harmful effects of
      development comes a spatial disarticulation between carbon-intensive production
      and consumption within as well as across societies. Implications for existing
      theory, methods and policy are discussed. 

PMID- 25769857
TI  - Like strangers we trust: identity and generic affiliation networks.
AB  - Sociological research on collective behavior provides strong evidence for the
      sources of collective action and shared attitudes based on overlapping
      experience. We know, for example, that members of social movement organizations
      are likely to share similar beliefs. However, a significant portion of the prior
      research on shared behaviors or attitudes analyzes individuals who do not know
      one another. This research using large surveys often infers overlapping
      experience based on generic connections: People in unions generally or church
      groups generally are likely to hold similar beliefs or engage in similar
      behaviors as if they were in the same unions or church groups. In this paper, I
      challenge this simple inference by arguing that the generic affiliations we hold
      contribute to our identity. Specifically, our identities can, in part, be seen as
      a network of overlapping roles based on generic affiliations. Findings indicate
      the importance of considering generic affiliation networks when modeling trust
      and political partisanship. Individuals who share multiple affiliations often
      appear to be similar to one another along a number of socio-demographic
      dimensions and report similar attitudes. Conclusions highlight the promise and
      challenge of relational approaches to social life. 

PMID- 25769858
TI  - Alcohol outlets, social disorganization, and robberies: accounting for
      neighborhood characteristics and alcohol outlet types.
AB  - We estimated spatially lagged regression and spatial regime models to determine
      if the variation in total, on-premise, and off-premise alcohol outlet(1) density
      is related to robbery density, while controlling for direct and moderating
      effects of social disorganization.(2) Results suggest that the relationship
      between alcohol outlet density and robbery density is sensitive to the
      measurement of social disorganization levels. Total alcohol outlet density and
      off-premise alcohol outlet density were significantly associated with robbery
      density when social disorganization variables were included separately in the
      models. However, when social disorganization levels were captured as a four item
      index, only the association between off-premise alcohol outlets and robbery
      density remained significant. More work is warranted in identifying the role of
      off-premise alcohol outlets and their characteristics in robbery incidents. 

PMID- 25769859
TI  - Do grandparents matter? A multigenerational perspective on educational attainment
      in Taiwan.
AB  - In response to the growing interest in multigenerational effects, we investigate
      whether grandparents' education affects grandchildren's transitions to academic
      high school and university in Taiwan. Drawing on social capital literature, we
      consider potential heterogeneity of the grandparent effect by parents'
      characteristics and propose that grandparents' education yields differential
      effects depending on parents' education. Our results show tenuous effects of
      grandmother's and grandfather's years of schooling, net of parents' education.
      However, the positive interaction effects between grandparents' and parents'
      years of schooling indicate that grandparents' additional years of schooling are
      more beneficial to students with more educated parents than for students with
      less educated parents. The diverging gap in the likelihood of attending academic
      high school or university between students with parents in higher and lower ends
      of the educational hierarchy, along with increased levels of grandparents'
      education, supports our hypothesis that grandparents' education augments
      educational inequality by parents' education. 

PMID- 25769860
TI  - The making of family values: developmental idealism in Gansu, China.
AB  - This paper examines the role of developmental thinking in the making of family
      values. We analyze survey data collected from Gansu Province in China with
      regular and multilevel logit models. The results show that individuals'
      endorsement of neolocal residence, self-choice marriage, gender egalitarianism,
      late marriage for women, and low fertility depends on the conjunction of
      preference for development and beliefs in its association with those family
      attributes, which we term developmental idealism associational evaluation.
      Furthermore, such impact of developmental thinking on family values holds robust
      in the presence of indigenous ideational forces, in this case Islamic religion.
      Although Islam influences family values in the opposite direction than
      developmental ideas do, the effect of Developmental Idealism associational
      evaluation does not differ significantly between Muslims and non-Muslims. 

PMID- 25769861
TI  - The bright side of migration: hedonic, psychological, and social well-being in
      immigrants in Spain.
AB  - The aim of this study was to examine the multi-dimensional structure of well
      being in immigrant population, as well as to explore the complexity of well-being
      disparities between immigrants and host nationals. We analyzed hedonic,
      psychological, and social well-being in a sample of 1250 immigrants from Bolivia,
      Colombia, Morocco, Romania and Sub-Saharan Africa, together with that of 500
      matched host nationals from Spain. Participants were selected by means of
      probability sampling with stratification by age and sex. Confirmatory factor
      analyses revealed that the re-specified tripartite model of well-being, including
      hedonic, psychological, and social components of the individual's functioning,
      was the best fitting model, as compared to alternative models. Importantly, after
      adjustment for perceived friendship and support, marital status, income, sex and
      age, immigrants presented higher levels of well-being than host nationals.
      Compared to host nationals, immigrants reported especially higher eudaimonic well
      being: social contribution and actualization, personal growth, self-acceptance,
      and purpose in life, and lower levels of well-being only in terms of positive
      relations with others and negative affect. These results are discussed in the
      context of positive psychology. 

PMID- 25769862
TI  - Convenience on the menu? A typological conceptualization of family food
      expenditures and food-related time patterns.
AB  - One of the most fundamental, but also controversial, food trends of the past
      years is convenience food. This article investigates the underexplored
      relationship between the heterogeneity in (convenience) food consumption (a
      feature of a food culture's cuisine) and meal patterns (characteristics of a food
      culture's structure). This study hopes to illustrate that convenience food can be
      interpreted both as a means to maintain a food culture's structure and as a means
      to overturn it. Latent Class Cluster Analysis is performed using data from the
      HBS 2005 survey on families' food expenditures to conceptualize convenience
      orientation and to examine the relationships with families' meal behaviors.
      Whereas outsourcing cooking is most prevalent among single-person households; two
      or more-person households are most likely to buy unprocessed and natural foods
      and to spend most time cooking and eating in. A higher consumption of convenience
      food is also more likely to affect individuals' kitchen than table habits. 

PMID- 25769863
TI  - Foreclosures and crime: a city-level analysis in Southern California of a dynamic
      process.
AB  - Although a growing body of research has examined and found a positive
      relationship between neighborhood crime and home foreclosures, some research
      suggests this relationship may not hold in all cities. This study uses city-level
      data to assess the relationship between foreclosures and crime by estimating
      longitudinal models with lags for monthly foreclosure and crime data in 128
      cities from 1996 to 2011 in Southern California. We test whether these effects
      are stronger in cities with a combination of high economic inequality and high
      economic segregation; and whether they are stronger in cities with high
      racial/ethnic heterogeneity and high racial segregation. One month, and
      cumulative three month, six month, and 12-month lags of foreclosures are found to
      increase city level crime for all crimes except motor vehicle theft. The effect
      of foreclosures on these crime types is stronger in cities with simultaneously
      high levels of inequality but low levels of economic segregation. The effect of
      foreclosures on aggravated assault, robbery, and burglary is stronger in cities
      with simultaneously high levels of racial heterogeneity and low levels of racial
      segregation. On the other hand, foreclosures had a stronger effect on larceny and
      motor vehicle theft when they occurred in a city with simultaneously high levels
      of racial heterogeneity and high levels of racial segregation. There is evidence
      that the foreclosure crisis had large scale impacts on cities, leading to higher
      crime rates in cities hit harder by foreclosures. Nonetheless, the economic and
      racial characteristics of the city altered this effect. 

PMID- 25769864
TI  - A loosening tray of sand? Age, period, and cohort effects on generalized trust in
      Reform-Era China, 1990-2007.
AB  - This study examines the transition of generalized trust in mainland China from
      1990 to 2007. Using the methodology of intrinsic estimator to analyze the
      repeated cross-sectional survey data from the World Values Survey, we separate
      age, period, and cohort effects on the extent of generalized trust of Chinese
      citizens. Empirical findings suggest that (1) There is a declining trend in the
      level of generalized trust across different periods from 1990 to 2007, net of age
      and cohort effects; (2) People's confidence in an ordinary social member
      increases as they age, a pattern resembling that of many Western societies; (3)
      The cohorts that experience the totalitarian Mao's Era in the formative stage of
      their life course stand out in evidently lower trust in generalized others,
      relative to those cohorts with formative stage falling in the Reform Era. 

PMID- 25769865
TI  - Do you see what I see? Perceptual variation in reporting the presence of disorder
      cues.
AB  - A growing body of literature considers the causes of variation in perceptions of
      disorder; thus far, few explanations are adequate. We ask: when exposed to the
      same environment, do individuals homogenously report the presence of the same
      disorder cues? Using a dataset that cluster samples residents within city blocks
      and hierarchal logistic regression, we assess whether individuals residing within
      1-2 blocks of each other report the same disorder cues. We find that (1) there is
      significant variation in reports, (2) individuals tend to disagree on the
      presence of disorder, not its absence, and (3) that reporting various disorder
      cues has significant ties to an individual's characteristics, their routine
      activities, and how attached they are to their neighborhood. How individuals
      report and interpret disorder seems to be dependent on the confluence of social,
      historical, economic, and place-based factors. Our results suggest revisiting the
      theorization of how individuals report on and interact with disorder. 

PMID- 25769866
TI  - Gatekeepers of the American Dream: how teachers' perceptions shape the academic
      outcomes of immigrant and language-minority students.
AB  - High school teachers evaluate and offer guidance to students as they approach the
      transition to college based in part on their perceptions of the student's hard
      work and potential to succeed in college. Their perceptions may be especially
      crucial for immigrant and language-minority students navigating the U.S.
      educational system. Using the Educational Longitudinal Study of 2002 (ELS:2002),
      we consider how the intersection of nativity and language-minority status may (1)
      inform teachers' perceptions of students' effort and college potential, and (2)
      shape the link between teachers' perceptions and students' academic progress
      towards college (grades and likelihood of advancing to more demanding math
      courses). We find that teachers perceive immigrant language-minority students as
      hard workers, and that their grades reflect that perception. However, these same
      students are less likely than others to advance in math between the sophomore and
      junior years, a critical point for preparing for college. Language-minority
      students born in the U.S. are more likely to be negatively perceived. Yet, when
      their teachers see them as hard workers, they advance in math at the same rates
      as nonimmigrant native English speaking peers. Our results demonstrate the
      importance of considering both language-minority and immigrant status as social
      dimensions of students' background that moderate the way that high school
      teachers' perceptions shape students' preparation for college. 

PMID- 25769867
TI  - Explaining attitudes about homosexuality in Confucian and non-Confucian nations:
      is there a 'cultural' influence?
AB  - The majority of research on attitudes about homosexuality has concentrated on the
      global North and on Christian and Muslim majority nations. Little research
      attention has been given to the factors that shape tolerance in societies with a
      Confucian heritage. Residents of Confucian counties are less tolerant than
      Europeans and Americans. One reason given for this difference is the emphasis on
      Confucian values in many Asian societies. Using data from the World Values
      Survey, we examine whether values that could be described as Confucian influence
      attitudes in Confucian and non-Confucian nations. We find a unique Confucian
      cultural effect, which can partially be explained with concerns about keeping the
      family intact. Conversely, in Confucian societies values related to obedience,
      conformity, and filial piety are unrelated to attitudes. There is also a small
      Buddhist contextual effect, resulting in more tolerant attitudes, and the
      Confucian influence cannot be reduced to an Asian regional effect. 

PMID- 25769868
TI  - State contexts and the criminalization of marital rape across the United States.
AB  - Spousal exemptions from rape prosecution persist in many US states' criminal
      codes thereby compromising women's rights to bodily self-control and personhood.
      Power resources theory-which emphasizes that given limited resources, groups act
      strategically to achieve goals-and gender stratification perspectives guided an
      event history analysis of the likelihood of marital rape criminalization in US
      states between 1978 and 2007. Findings suggest criminalization is influenced by
      the expected marginal benefit of law reform, women's relative socioeconomic
      resources, and racial heterogeneity. This research highlights the importance of
      considering how existing laws, group resources, and intersecting social cleavages
      influence the expansion of women's rights. 

PMID- 25769869
TI  - The African Development Bank and women's health: a cross-national analysis of
      structural adjustment and maternal mortality.
AB  - We conduct a cross-national analysis to test the hypothesis that African
      Development Bank (AfDB) structural adjustment lending adversely impacts maternal
      mortality in Sub-Saharan Africa. We analyze data for thirty-five Sub-Saharan
      African nations with up to four time points (1990, 1995, 2000, and 2005) with
      generalized least squares random effects regression models and modified two-step
      Heckman models that correct for potential endogeneity regarding whether or not a
      Sub-Saharan African nations receives an AfDB structural adjustment loan. We find
      support for our hypothesis that indicates that Sub-Saharan African nations that
      receive an AfDB structural adjustment loan tend to have higher levels of maternal
      mortality than Sub-Saharan African nations that do not receive such a loan. This
      finding remains stable even when controlling for endogeneity. We conclude by
      talking about the theoretical and methodological implications along with possible
      directions for future research. 

PMID- 25769870
TI  - Anti-minority attitudes and Tea Party Movement membership.
AB  - In 2009, shortly after the election of the United States' first black President,
      a new protest movement emerged. When some supporters of this new Tea Party
      Movement (TPM) expressed their ire with race-laden messages various commentators
      suggested that racism may be a major motive for TPM activism. Accordingly, this
      study draws on national survey data to examine the extent to which racial
      attitudes and conservative ideology are associated with self-declared membership
      in the TPM while controlling for contextual factors that have proven influential
      in other rightist movement research. Key findings reveal that aside from
      conservative political ideology, racial resentment is indeed among the strongest
      predictors of TPM membership. Supplemental analyses explore the extent to which
      conservatives differ from TPM members. The results show that very conservative
      individuals and TPM members evince similar attitudes. The findings are discussed
      in terms of contemporary race relations and the implications for future social
      movement research. 

PMID- 25769871
TI  - The importance of survey content: testing for the context dependency of the New
      Ecological Paradigm Scale.
AB  - Using a regression-based analysis of a survey of U.S. households, we demonstrate
      that both environmental concern, as measured by the New Ecological Paradigm (NEP)
      Scale, and facets of environmental concern, as measured by three NEP factors, are
      influenced by survey context. Survey respondents were presented with detailed
      information about two to four threatened and endangered marine species in the
      United States, including the Endangered Species Act listing status of the species
      and threats to the survival of the species. All else being equal, measures of
      environmental concern are influenced by both which species were included in the
      survey and by the concern expressed about these species. As such, measures of
      environmental concern are found to be context dependent since they are correlated
      with the species included in each survey. We also demonstrate that NEP-based
      measures of environmental concern are affected by socio-demographic variables,
      opinions about government spending, and environmental knowledge. Given the wide,
      multi-disciplinary use of the NEP Scale, it is important for researchers to
      recognize that NEP-based measures of environmental concern may be sensitive to
      information included in surveys. 

PMID- 25769872
TI  - Equality and quality in education. A comparative study of 19 countries.
AB  - This contribution assesses the performance of national education systems along
      two important dimensions: The degree to which they help individuals develop
      capabilities necessary for their successful social integration (educational
      quality) and the degree to which they confer equal opportunities for social
      advancement (educational equality). It advances a new conceptualization to
      measure quality and equality in education and then uses it to study the
      relationship between institutional differentiation and these outcomes. It relies
      on data on final educational credentials and literacy among adults that
      circumvent some of the under-appreciated conceptual challenges entailed in the
      widespread analysis of international student assessment data. The analyses reveal
      a positive relationship between educational quality and equality and show that
      education systems with a lower degree of institutional differentiation not only
      provide more educational equality but are also marked by higher levels of
      educational quality. While the latter association is partly driven by other
      institutional and macro-structural factors, I demonstrate that the higher levels
      of educational equality in less differentiated education systems do not entail an
      often-assumed trade-off for lower quality. 

PMID- 25769873
TI  - Threat, prejudice and the impact of the riots in England.
AB  - This paper examines how a major outbreak of rioting in England in 2011 impacted
      on prejudice toward three minority groups in Britain: Muslims, Black British and
      East Europeans. We test whether the riots mobilized individuals by increasing
      feelings of realistic and symbolic threat and ultimately prejudice, or whether
      the riots galvanized those already concerned about minorities, thus strengthening
      the relationship between threat and prejudice. We conducted three national
      surveys - before, after and one year on from the riots - and show that after the
      riots individuals were more likely to perceive threats to society's security and
      culture, and by extension express increased prejudice toward Black British and
      East European minorities. We find little evidence of a galvanizing impact. One
      year later, threat and prejudice had returned to pre-riots levels; however,
      results from a survey experiment show that priming memories of the riots can
      raise levels of prejudice. 

PMID- 25769874
TI  - Clinical outcome of scaphoid malunion as a result of scaphoid fracture nonunion
      surgical treatment: A 5-year minimum follow-up study.
AB  - BACKGROUND: Although malunion resulting from reconstruction for scaphoid fracture
      nonunion is a typical complication, there has been little consideration regarding
      its clinical outcomes. HYPOTHESIS: The quality of restoration of the scaphoid
      anatomy may have little effect on clinical outcomes. MATERIALS AND METHODS:
      Twenty-five patients with scaphoid fracture nonunion underwent curettage and
      internal fixation with bone grafting performed by a single surgeon, and they were
      followed up for a minimum of 5 years. Some of these patients comprised the
      malunion group if the height/length ratio (H/L ratio) in the most central
      longitudinal computed tomographic image was more than 0.6. We compared the
      clinical outcomes of the malunion group with a well-union group based on various
      clinical scores (Patient Evaluation Measure, Disabilities of the Arm, Shoulder
      and Hand, modified Mayo wrist scoring system). RESULTS: The average follow-up
      period was 81 months (range: 65-110), and 15 cases among the 25 patients were
      included in the malunion group. There were no statistical differences in the
      clinical scores between malunions (15 cases) and well unions (10 cases), and
      there was no correlation between the H/L ratios and the clinical outcomes.
      CONCLUSION: The clinical outcomes of malunited scaphoids after reconstruction for
      scaphoid fractures nonunion did not differ significantly from well-united
      scaphoids at a minimum 5-year follow-up.

PMID- 25769875
TI  - Coping strategies employed by women with endometriosis in a public health-care
      setting.
AB  - This study explored how South African patients attending public health facilities
      reported coping with endometriosis. A total of 16 women with endometriosis were
      interviewed, and we explored how participants coped with endometriosis. All
      interviews were audio-recorded and transcribed. Thematic analysis was used to
      identify themes. Participants reported employing both problem-focused and emotion
      focused strategies to cope with endometriosis. Problem-focused strategies
      included limiting physical activities, increasing knowledge about endometriosis,
      scheduling social and work activities around menstrual cycle, engaging in self
      management and relying on social support. Emotion-focused coping strategies
      included accepting the disease, adopting a positive attitude, engaging in self
      talk and evoking spirituality.

PMID- 25769876
TI  - Meal ingestion markedly increases liver stiffness suggesting the need for liver
      stiffness determination in fasting conditions.
AB  - INTRODUCTION: The introduction of noninvasive liver stiffness (LS) determination
      has heralded a new stage in the diagnosis and treatment of liver fibrosis. AIM:
      We evaluated the effect of food intake on LS in patients with different degrees
      of liver disease. PATIENTS AND METHODS: We evaluated 24 patients (F<=1, n=11 and
      F> 1, n=13). LS (Fibroscan(r)) and portal blood flow (PBF) (Doppler ultrasound)
      were studied before and 30min after ingestion of a standard liquid meal. RESULTS:
      Food intake increased PBF (51+/-10%, p<0.001). Splanchnic hyperemia was
      accompanied by a significant rise in LS (from 7.8+/-3.3 to 10.3+/-4.1kPa,
      p<0.001). These increases were similar in patients with minimal fibrosis(F<=1)
      and in those with more advanced fibrosis or cirrhosis (F>1). Hemodynamic and LS
      values returned to baseline pre-meal levels within 2hours. CONCLUSION: LS
      increases markedly after ingestion of a standard meal, irrespective of the degree
      of fibrosis. Our results strongly suggest that LS should be measured in fasting
      conditions.

PMID- 25769877
TI  - [Characterization, influence and manipulation of the gastrointestinal microbiota
      in health and disease].
AB  - The gastrointestinal tract harbors trillions of microorganisms that are
      indispensable for health. The gastrointestinal microbiota can be studied using
      culture and molecular methods. The applications of massive sequencing are
      constantly increasing, due to their high yield, increasingly accessible costs,
      and the availability of free software for data analysis. The present article
      provides a detailed review of a large number of studies on the gastrointestinal
      microbiota and its influence on human health; particular emphasis is placed on
      the evidence suggesting a relationship between the gastrointestinal microbial
      ecosystem and diverse physiological and immune/inflammatory processes. Discussion
      of the articles analyzed combines a medical approach and current concepts of
      microbial molecular ecology. The present revision aims to be useful to those
      interested in the gastrointestinal microbiota and its possible alteration to
      maintain, re-establish and enhance health in the human host.

PMID- 25769878
TI  - Skeletal muscle findings in experimental autoimmune encephalomyelitis.
AB  - INTRODUCTION: Skeletal muscle is a target organ in multiple sclerosis, a chronic
      debilitating disease of the central nervous system caused by demyelination and
      axonal deterioration. Since the experimental autoimmune encephalomyelitis model
      reproduces the relapsing-remitting course found in most multiple sclerosis
      patients, this model was used to compare the histological features of skeletal
      muscle at onset with those observed at the start of the second relapse. MATERIAL
      AND METHODS: Histological, histochemical and ultrastructural changes, as well as
      biochemical oxidative damage and antioxidant-system markers, were examined in the
      soleus and extensor digitorum longus muscles of Dark Agouti rats in which
      experimental autoimmune encephalomyelitis had been induced by active immunization
      using myelin oligodendrocyte glycoprotein. RESULTS: Histological examination at
      disease onset revealed ragged-red fibers and ultrastructural evidence of
      mitochondrial degeneration. At the second relapse, neurogenic changes included a
      wide range of cytoarchitectural lesions, skeletal muscle atrophy and the
      appearance of intermediate fibers; however, differences were observed between
      soleus and extensor digitorum longus lesions. Biochemical tests disclosed an
      increase in oxidative stress markers at onset, which was more pronounced at the
      second relapse. CONCLUSIONS: Microscopic findings suggest that two patterns can
      be distinguished at disease onset: an initial phase characterized by muscle
      mitochondrial alterations, and a second phase dominated by a histological muscle
      pattern of clearly neurogenic origin.

PMID- 25769879
TI  - Cirrhosis increases mortality and splenectomy rates following splenic injury.
AB  - BACKGROUND: Cirrhosis may be a risk factor for mortality following blunt splenic
      injury (BSI) and it predicts the need for an operative intervention. METHODS: We
      performed a case-control study at 3 level 1 trauma centers. Comparisons were made
      with chi-square test, Wilcoxon rank-sum test, and binary logistic regression, and
      stratified by propensity for splenectomy. Data are presented as odds ratios (ORs)
      and 95% confidence intervals (95% CIs). RESULTS: Mortality was 27% (21/77) and
      cirrhosis was a strong risk factor for death (OR 8.8, 95% CI 3.7 to 21.1).
      Compared with controls, cirrhosis was an independent risk factor for splenectomy
      (OR 5.4, 95% CI 2.5 to 11.5), and only splenic injury grade was associated with
      splenectomy (OR 2.2, 95% CI 1.3 to 3.6). Only admission model for end-stage liver
      disease was independently associated with mortality after an operation (OR 1.7,
      95% CI 1.1 to 2.8). After propensity score matching, we found no association
      between splenectomy and mortality in cirrhotic patients. CONCLUSION: Cirrhosis
      dramatically increases mortality and the odds of an operative intervention in BSI
      patients with pre-existing cirrhosis, and BSI requires vigilant attention and
      early intervention should be considered.

PMID- 25769880
TI  - Can general surgeons evaluate visceral slide with transabdominal ultrasound to
      predict safe sites for primary laparoscopic port placement? A prospective study
      of sonographically naive operators at a tertiary center.
AB  - BACKGROUND: Port placement injuries are a potentially devastating complication of
      laparoscopic surgery. Ultrasound assessment for visceral slide has the ability to
      preoperatively determine adhesion-free areas. The utility of this technique has
      not been studied when performed by surgeons. METHODS: Surgeons without expertise
      in ultrasound were taught the visceral slide technique. Patients with a history
      of abdominal surgery were then assessed for adhesion-free areas on the abdominal
      wall. Ultrasound assessments were validated against intraoperative visualization.
      RESULTS: Nine surgeons using the visceral slide technique assessed 145 patients
      for the presence of adhesions immediately before surgery. Surgeon who performed
      ultrasound demonstrated a sensitivity of 69.6%, specificity of 98.7%, and
      positive predictive value of 99.5% for detection of areas free from critical
      adhesions. The median time to perform the examination was 2 minutes. CONCLUSION:
      The visceral slide technique was easily learned, was rapid to perform, and
      reliably identified adhesion-free areas of the abdominal wall.

PMID- 25769881
TI  - Video-assisted thoracic surgery versus pleural drainage in the management of the
      first episode of primary spontaneous pneumothorax.
AB  - BACKGROUND: The aim of the study was to analyze the cost-effectiveness outcomes
      of video-assisted thoracic surgery (VATS) in the treatment of primary spontaneous
      pneumothorax (PSP), comparing the minimally invasive procedure with pleural
      drainage (PD). METHODS: Between July 2006 and October 2012, we treated 122
      patients with a first episode of PSP by VATS (61 patients) or pleural drainage
      (61 patients). We established the relationship between costs and quality-adjusted
      life (QAL) for both techniques. RESULTS: The total cost per patient of minimally
      invasive procedure was more advantageous than that of chest tube (?2,422.96 vs
      ?4,855.12). The QAL expectancy of VATS was longer than that of PD (57.00 vs 40.80
      at 60 months). The QAL year of VATS (.32 at 1st year and .25 at 5th year) was
      better than that of PD. Incremental cost-effectiveness ratio of VATS versus PD
      was between ?7,600.00 (1st year) and ?10,045.00 (5th year), remaining well below
      the threshold of acceptability. CONCLUSION: VATS as the first-line treatment for
      PSP allowed low morbidity, short hospitalization, and excellent quality of life.

PMID- 25769883
TI  - Intravenous or oral administration of vinorelbine in adjuvant chemotherapy with
      cisplatin and vinorelbine for resected NSCLC.
AB  - OBJECTIVES: Cisplatin and vinorelbine given intravenously is a well-established
      adjuvant chemotherapy regimen after surgery for early-stage NSCLC. Vinorelbine
      can also be administered orally. However, the efficacy of orally administrated
      vinorelbine in adjuvant treatment of NSCLC is unknown. We assessed the overall
      survival (OS) and disease-free survival (DFS) of patients treated with adjuvant
      i.v. vinorelbine or p.o. vinorelbine, in combination with i.v. cisplatin.
      MATERIALS AND METHODS: We reviewed two time-separated cohorts of patients
      referred to the Department of Oncology at Aarhus University Hospital (Denmark)
      from 2005 to 2012 for adjuvant chemotherapy after surgery for NSCLC. RESULTS AND
      CONCLUSION: Of the 265 patients included in this study, 126 patients received
      i.v. and 139 received p.o. vinorelbine/cisplatin. The two groups were comparable
      with respect to important baseline characteristics. Median OS for all patients
      was 78.7 months and the median DFS was 35.7 months. No statistically significant
      difference in OS or DFS for patients treated with i.v. or oral vinorelbine was
      detected. The DFS rates of the two groups were comparable across all variables in
      subgroup analysis. In conclusion we observed that intravenous or oral
      administration of vinorelbine in combination with cisplatin after surgery for
      NSCLC appear equally effective in terms of overall and disease-free survival.

PMID- 25769882
TI  - Re-expression of LKB1 in LKB1-mutant EKVX cells leads to resistance to paclitaxel
      through the up-regulation of MDR1 expression.
AB  - OBJECTIVES: The tumor suppressor LKB1 has recently been shown to be involved in
      the regulation of microtubule dynamics, thus cancer cells with inactivated LKB1
      may have developed a means to overcome dysregulated microtubule functions, making
      them intrinsically resistant to microtubule targeting agents. Here, we generated
      isogenic LKB1-wild type and mutant non-small cell lung cancer (NSCLC) cell lines
      to evaluate the role of LKB1 in paclitaxel resistance. MATERIALS AND METHODS:
      SRB, flow cytometry and immunoblotting were used to assess cell proliferation and
      apoptosis in NSCLC cell lines after paclitaxel treatment. Expression of LKB1 was
      restored in LKB1-null cells by retrovirus infection and was reduced in LKB1-wild
      type cells by shRNA knock down. RESULTS AND CONCLUSION: The restoration of LKB1
      in LKB1-null cells failed to promote paclitaxel-induced apoptosis in both p53
      wild type and p53-mutant backgrounds, indicating that LKB1 was not required for
      paclitaxel-induced apoptosis. Interestingly, the re-establishment of LKB1
      expression led to the up-regulation of class III beta-tubulin and MDR1 in EKVX
      cells. The up-regulation of MDR1 protein and transcripts in EKVX cells was
      specifically associated with the expression of wild-type LKB1 and mainly
      responsible for the increased cellular resistance to paclitaxel. However, the
      presence of LKB1 protein was not required to maintain this increased MDR1
      expression even though there was no genetic amplification or promoter de
      methylation of the ABCB1 locus in EKVX-LKB1-WT cells. These data suggest that
      LKB1 does not promote paclitaxel-induced apoptosis in most NSCLC cell lines. In
      contrast, in some NSCLC, the presence of LKB1 may facilitate increases in either
      MDR1 or class III beta-tubulin expression which can lead to paclitaxel
      resistance.

PMID- 25769885
TI  - An unusual perineal plaque.
AB  - We present the case of a 61-year-old male with a long-standing perineal and
      scrotal lesion. Investigations eventually revealed cutaneous tuberculosis, with
      complete resolution after appropriate treatment. It highlights the variable
      presentation of cutaneous tuberculosis and the importance of considering the
      diagnosis in chronic lesions. 

PMID- 25769884
TI  - Defense-in-depth by mucosally administered anti-HIV dimeric IgA2 and systemic
      IgG1 mAbs: complete protection of rhesus monkeys from mucosal SHIV challenge.
AB  - Although IgA is the most abundantly produced immunoglobulin in humans, its role
      in preventing HIV-1 acquisition, which occurs mostly via mucosal routes, remains
      unclear. In our passive mucosal immunizations of rhesus macaques (RMs), the anti
      HIV-1 neutralizing monoclonal antibody (nmAb) HGN194, given either as dimeric
      IgA1 (dIgA1) or dIgA2 intrarectally (i.r.), protected 83% or 17% of the RMs
      against i.r. simian-human immunodeficiency virus (SHIV) challenge, respectively.
      Data from the RV144 trial implied that vaccine-induced plasma IgA counteracted
      the protective effector mechanisms of IgG1 with the same epitope specificity. We
      thus hypothesized that mucosal dIgA2 might diminish the protection provided by
      IgG1 mAbs targeting the same epitope. To test our hypothesis, we administered
      HGN194 IgG1 intravenously (i.v.) either alone or combined with i.r. HGN194 dIgA2.
      We enrolled SHIV-exposed, persistently aviremic RMs protected by previously
      administered nmAbs; RM anti-human IgG responses were undetectable. However, low
      level SIV Gag-specific proliferative T-cell responses were found. These animals
      resemble HIV-exposed, uninfected humans, in which local and systemic cellular
      immune responses have been observed. HGN194 IgG1 and dIgA2 used alone and the
      combination of the two neutralized the challenge virus equally well in vitro. All
      RMs given only i.v. HGN194 IgG1 became infected. In contrast, all RMs given
      HGN194 IgG1+dIgA2 were completely protected against high-dose i.r. SHIV-1157ipEL
      p challenge. These data imply that combining suboptimal defenses at the mucosal
      and systemic levels can completely prevent virus acquisition. Consequently,
      active vaccination should focus on defense-in-depth, a strategy that seeks to
      build up defensive fall-back positions well behind the fortified frontline. 

PMID- 25769886
TI  - Herpes simplex virus type 2 (HSV-2) genital shedding in HSV-2-/HIV-1-co-infected
      women receiving effective combination antiretroviral therapy.
AB  - The dynamics of genital shedding of HSV-2 DNA was assessed in HIV-1-infected
      women taking combination antiretroviral therapy (cART). HIV-1 RNA, HIV-1 DNA and
      HSV DNA loads were measured during 12-18 months using frozen plasma, PBMC and
      cervicovaginal lavage samples from 22 HIV-1-infected women, including 17 women
      naive for antiretroviral therapy initiating cART and 5 women with virological
      failure switching to a new regimen. Nineteen (86%) women were HSV-2-seropositive.
      Among HSV-2-/HIV-1-co-infected women, HIV-1 RNA loads showed a rapid fall from
      baseline after one month of cART, in parallel in paired plasma and cervicovaginal
      secretions. In contrast, HIV-1 DNA loads did not show significant variations from
      baseline up to 18 months of treatment in both systemic and genital compartments.
      HSV DNA was detected at least once in 12 (63%) of 19 women during follow up: HSV
      2 shedding in the genital compartment was observed in 11% of cervicovaginal
      samples at baseline and in 16% after initiating or switching cART. Cervicovaginal
      HIV-1 RNA loads were strongly associated with plasma HIV-1 RNA loads over time,
      but not with cervicovaginal HSV DNA loads. Reactivation of genital HSV-2
      replication frequently occurred despite effective cART in HSV-2-/HIV-1-co
      infected women. Genital HSV-2 replication under cART does not influence
      cervicovaginal HIV-1 RNA or DNA shedding. 

PMID- 25769887
TI  - HIV diagnosis in a patient presenting with vasculitis.
AB  - A patient with digital ischaemia and gangrene was treated with iloprost and
      antiplatelets for two weeks. His vasculitic screen was negative except for a
      positive HIV test. His vasculitis improved three weeks after treatment with
      antiretroviral medications. Though vasculitis is well known to be associated with
      HIV infection, very few cases of HIV present as vasculitis. 

PMID- 25769888
TI  - Value of CXCL13 in diagnosing asymptomatic neurosyphilis in HIV-infected
      patients.
AB  - Diagnosing asymptomatic neurosyphilis (ANS) in HIV-infected patients is
      difficult. A recent report suggested that CXCL13 is a promising diagnostic marker
      for neurosyphilis in HIV-positive patients. However, whether CXCL13 can be a
      diagnostic marker for ANS in HIV-infected patients remains unknown. The purpose
      of our study was to determine the role of CXCL13 in diagnosing ANS in HIV
      infected patients. This study comprised two study and three control groups. Two
      study groups included 12 HIV-infected patients with ANS and 25 patients with
      syphilis and HIV co-infection (without ANS). Three control groups included 9
      patients with ANS without HIV infection, 25 HIV-infected patients without
      syphilis and 10 healthy volunteers. Concentrations of CSF CXCL13 were measured
      before and after neurosyphilis therapy. Our results showed that CSF CXCL13
      concentrations were significantly increased in all of the HIV-infected patients
      with ANS, the 25 HIV patients with syphilis and the 9 ANS patients without HIV,
      but not in the patients of the other two control groups. CSF CXCL13
      concentrations declined in the two study groups of patients following
      neurosyphilis therapy. Therefore, CSF CXCL13 concentrations could improve the
      diagnosis of ANS in HIV-infected patients. 

PMID- 25769889
TI  - Sexual health screening in people living with HIV--are we getting the whole
      story?
AB  - Patients' notes were audited to evaluate sexual health screening in 385 people
      living with HIV. A total of 76% were offered sexually transmitted infection (STI)
      screening; 85% of these accepted; 62% reported regular partners of whom 44% were
      also people living with HIV. In men who have sex with men (MSM), 64% reported
      consistent condom use for anal sex; of these, 15% had rectal STIs diagnosed. Of
      all patients, 62% reported monogamous relationships; in this MSM sub-group, 12%
      had STIs diagnosed. STIs are still being diagnosed despite continued safe sex
      messages and significantly in those reporting monogamous relationships and
      consistent condom use. Sexual history and safe sex education should be integral
      to routine care and STI screening offered annually regardless of sexual history
      as recommended by 2013 British HIV Association Standards of Care for People
      Living with HIV. More frequent STI screening may be required in high-risk
      patients.

PMID- 25769890
TI  - Cycloartenol triterpenoid saponins from Cimicifuga simplex (Ranunculaceae) and
      their biological effects.
AB  - The constituents of Cimicifuga plants have been extensively investigated, and the
      principal metabolites are 9,19-cyclolanostane triterpenoid glycosides, which are
      distributed widely in Cimicifuga plants, but not in other members of the
      Ranunculaceae family, and are considered to be characteristics of the Cimicifuga
      genus. This type of triterpenoid glycoside possesses several important biological
      activities. More than 120 cycloartane triterpene glycosides have been isolated
      from Cimicifuga simplex Wormsk. The aim of this review article is to summarize
      all the major findings based on the available scientific literatures on C.
      simplex, with a focus on the identified 9,19-cyclolanostane triterpenoid
      glycosides. Biological studies of cycloartane triterpene glycosides from
      Cimicifuga spp. are also discussed. 

PMID- 25769891
TI  - Comparative analysis of rapamycin biosynthesis clusters between Actinoplanes sp.
      N902-109 and Streptomyces hygroscopicus ATCC29253.
AB  - The present study was designed to identify the difference between two rapamycin
      biosynthetic gene clusters from Streptomyces hygroscopicus ATCC29253 and
      Actinoplanes sp. N902-109 by comparing the sequence and organization of the gene
      clusters. The biosynthetic gene cluster for rapamycin in Streptomyces
      hygroscopicus ATCC29253 was reported in 1995. The second rapamycin producer,
      Actinoplanes sp. N902-109, which was isolated in 1995, could produce more
      rapamycin than Streptomyces hygroscopicus ATCC29253. The genomic map of
      Actinoplanes sp. N902-109 has been elucidated in our laboratory. Two gene
      clusters were compared using the online software anti-SMASH, Glimmer 3.02 and
      Subsystem Technology (RAST). Comparative analysis revealed that the organization
      of the multifunctional polyketide synthases (PKS) genes: RapA, RapB, RapC, and
      NRPS-like RapP were identical in the two clusters. The genes responsible for
      precursor synthesis and macrolactone modification flanked the PKS core region in
      N902-109, while the homologs of those genes located downstream of the PKS core
      region in ATCC29253. Besides, no homolog of the gene encoding a putative type II
      thioesterase that may serve as a PKS "editing" enzyme accounted for over
      production of rapamycin in N902-109, was found in ATCC29253. Furthermore, no
      homologs of genes rapQ (encoding a methyltransferase) and rapG in N902-109 were
      found in ATCC29253, however, an extra rapM gene encoding methyltransferase was
      discovered in ATCC29253. Two rapamycin biosynthetic gene clusters displayed
      overall high homology as well as some differences in gene organization and
      functions. 

PMID- 25769892
TI  - Antithrombotic effects of the effective components group of Xiaoshuantongluo
      formula in vivo and in vitro.
AB  - The present study was designed to investigate the antithrombotic effects and
      underlying mechanisms of the effective components group (ECG) of Xiaoshuantongluo
      recipe (XECG) and to further verify the rationality and feasibility of ECG-guided
      methodology in traditional Chinese medicine (TCM) research. The arterial
      thrombosis model induced by ferric chloride (FeCl3) oxidation and the venous
      thrombosis model induced by inferior vena cava ligation were established to
      evaluate the antithrombotic potential of XECG. Our results indicated that XECG
      significantly prolonged the time to occlusion, activated partial thromboplastin
      time (APTT), and prothrombin time (PT), and markedly inhibited adenosine
      diphosphate (ADP)-induced platelet aggregation in the 20% FeCl3-induced arterial
      thrombosis model. The superoxide dismutase (SOD) activity was significantly
      increased and the levels of malondialdehyde (MDA) and nitric oxide (NO) were
      dramatically decreased in the plasma of arterial thrombosis rats after XECG
      treatment for 12 days. Furthermore, XECG markedly reduced the weight of thrombus
      formed by inferior vena cava ligation. Additionally, XECG exhibited 2,2-diphenyl
      1-picrylhydrazyl (DPPH) free radical scavenging activity and protective effect on
      mitochondrial lipid peroxidation. In summary, XECG played an important role in
      the prevention of thrombosis through interacting with multiple targets, including
      inhibition of platelet aggregation and coagulation and repression of oxidative
      stress. The ECG-guided methodology was validated as a feasible tool in TCM
      research. 

PMID- 25769893
TI  - A network pharmacology study of Sendeng-4, a Mongolian medicine.
AB  - We collected the data on the Sendeng-4 chemical composition corresponding targets
      through the literature and from DrugBank, SuperTarget, TTD (Therapeutic Targets
      Database) and other databases and the relevant signaling pathways from the KEGG
      (Kyoto Encyclopedia of Genes and Genomes) database and established models of the
      chemical composition-target network and chemical composition-target-disease
      network using Cytoscape software, the analysis indicated that the chemical
      composition had at least nine different types of targets that acted together to
      exert effects on the diseases, suggesting a "multi-component, multi-target"
      feature of the traditional Mongolian medicine. We also employed the rat model of
      rheumatoid arthritis induced by Collgen Type II to validate the key targets of
      the chemical components of Sendeng-4, and three of the key targets were validated
      through laboratory experiments, further confirming the anti-inflammatory effects
      of Sendeng-4. In all, this study predicted the active ingredients and targets of
      Sendeng-4, and explored its mechanism of action, which provided new strategies
      and methods for further research and development of Sendeng-4 and other
      traditional Mongolian medicines as well. 

PMID- 25769894
TI  - The reproductive toxicity of saponins isolated from Cortex Albiziae in female
      mice.
AB  - Saponin frsom Cortex Albiziae (SCA) are extensively used in the clinical
      treatment of tumor and depression. However, SCA may cause several adverse
      effects, including reproductive toxicity. The present study was designed to
      assess the mechanism by which SCA cause reproductive toxicity in female mice. The
      general reproductive toxicity testing was accomplished in female Kunming mice.
      The animals were divided into four groups: three groups that were treated by oral
      gavage with 135, 270, and 540 mg.kg(-1).d(-1) of SCA prepared in physiological
      saline, respectively, and one vehicle control group that was treated with
      physiological saline only. The gestational toxicity tests were conducted at 540
      mg.kg(-1).d(-1). The general reproductive toxicity results showed that the
      pregnancy rate of the SCA-treated group decreased with the pregnancy rate being
      decreased by 70% at 540 mg.kg(-1).d(-1). SCA elicited maternal toxicity in the
      ovary and the uterus, but no fetal toxicity or teratogenicity was observed. The
      rates of implantation in the early, middle, and late pregnancy were all
      decreased, with stillbirths and maternal deaths being observed. Histopathological
      changes showed that SCA adversely affected the ovary and the uterus. In
      conclusion, SCA-induced reproductive toxicity in female mice is most likely
      caused by its damage to the ovary and the uterus. 

PMID- 25769896
TI  - Chemical constituents of Allophylus africanus.
AB  - Four new compounds, alloeudesmenol (1), hanocokinoside (3), allotaraxerolide (4),
      and alloaminoacetaldehyde (5), together with two known compound, stigmastane
      3beta,4beta-diol (2) and pinitol 6 (a and b) were isolated and identified from
      the whole plant of Allophylus africanus. 

PMID- 25769895
TI  - Astragaloside IV prevents lipopolysaccharide-induced injury in H9C2
      cardiomyocytes.
AB  - This study aimed to investigate the protective effects of astragaloside IV (AS
      IV) on lipopolysaccharide (LPS)-induced injury in H9C2 cardiomyocytes. H9C2
      Cardiomyocytes were cultured with LPS (10 MUg.mL(-1)) for 4 h and treated with AS
      IV at 50, 100, and 150 MUmol.L(-1) for various durations. Cell viability was
      determined by MTT. The content of released TNF-alpha and IL-6 from cardiomyocytes
      were evaluated by enzyme-linked immunosorbent assay (ELISA). The levels of
      superoxidase dismutase (SOD), malondialdehyde (MDA), lactate dehydrogenase (LDH),
      and creatine phosphate kinase (CK) were measured by using commercial available
      kits. The mRNA and protein expression levels of NF-kappaB p65 were measured by RT
      PCR and Western blotting, respectively. And the NF-kappaB p65 activity was
      measured by ELISA. Our results demonstrated that AS IV at 50, 100, and 150
      MUmol.L(-1) markedly inhibited the release of TNF-alpha and IL-6 and decreased NF
      kappaB expression, compared with the model group. Moreover, the improved SOD
      activity and decreased MDA, LDH and CK levels were detected after AS IV
      treatment. In summary, AS IV could increase the activities of antioxidant
      enzymes, inhibite lipid peroxidation, and down-regulate the inflammatory
      mediators involved in the inflammatory responses. These results demonstrated that
      AS IV could prevent LPS-induced injury in cardiomyocytes. 

PMID- 25769897
TI  - Chemical constituents from Mongolian herb Syringa pinnatifolia var. alashanensis.
AB  - Two new sesquiterpenes, innatifolone A (1) and pinnatifolone B (2), along with 6
      known compounds, furostan (3), isocalamendiol (4), pluviatolide (5), (8S,8'R,9S)
      cubebin (6), 2-(4-hydroxy-3-methoxybenzyl)-3-(3,4-dimethoxybenzyl)
      tetrahydrofuran (7), and methyl 3-acetoxy-12-oleanen-28-oate (8), were isolated
      from Mongolian herb Syringa pinnatifolia. 

PMID- 25769898
TI  - Metabolite profiling of Zi-Shen pill in rat biological specimens by UPLC-Q
      TOF/MS.
AB  - This study aimed to profile the chemical constituents of Zi-Shen pill (ZSP) and
      its metabolites in plasma, urine, and prostate tissue, after administration into
      rats. Based on the chromatographic retention behavior, fragmentation patterns of
      chemical components, published literatures, and literature databases, an UPLC-Q
      TOF/MS (LC-TOF/MS) method was established to identify the components of ZSP and
      its metabolites in biological samples. A total of 101 compounds were identified
      and tentatively characterized from the ZSP, including alkaloids, xanthones, and
      timosaponins. Except for 33 prototype components, 22 metabolites were detected in
      the plasma, urine, and prostate, and mainly came from Phellodendri Amurensis
      Cortex and Anemarrhenae Rhizoma. It was found that glucuronidation and sulfation
      were the major metabolic processes of xanthones, while oxidation, demethylation,
      and glucuronidation were the major metabolic pathways of alkaloids. In summary,
      the present study provided important chemical information on the metabolism of
      ZSP, indicating that alkaloids might be able to be absorbed into the prostate.
      The results provided a basis for further studies of the mechanisms of action for
      ZSP. 

PMID- 25769899
TI  - Mercury speciation in seawater by liquid chromatography-inductively coupled
      plasma-mass spectrometry following solid phase extraction pre-concentration by
      using an ionic imprinted polymer based on methyl-mercury-phenobarbital
      interaction.
AB  - Trace levels of inorganic mercury, methyl-mercury and ethyl-mercury have been
      assessed in seawater by high performance liquid chromatography (HPLC) hyphenated
      with inductively coupled plasma-mass spectrometry (ICP-MS) after solid phase
      extraction (SPE) pre-concentration with a novel synthesized ionic imprinted
      polymer. The adsorbent material was prepared by trapping a non-vinylated
      chelating ligand (phenobarbital) via imprinting of a ternary mixed ligand complex
      of the non-vinylated chelating agent, the template (methyl-mercury), and the
      vinyl ligand (metacrylic acid, MAA). Ethylene dimetacrylate (EDMA) and 2,2'
      azobisisobutyronitrile (AIBN) were used as cross-linker and initiator reagents,
      respectively; and the precipitation polymerization technique was used in a
      porogen of acetonitrile/water (4:1). The best retention properties for methyl
      mercury, inorganic mercury and ethyl-mercury species from seawater were obtained
      when loading 200 mL of sample adjusted to pH 8.0 and at a flow rate of 2.0 mL
      min(-1) on a column-packed with 200mg of the material. Quantitative mercury
      species recoveries were obtained using 4 mL of an eluting solution consisting of
      0.8% (v/v) 2-mercaptoethanol and 20% (v/v) methanol (pH adjusted to 4.5) pumped
      at a flow rate of 2.0 mL min(-1). Mercury species separation was achieved on a
      Kinetex C18 column working under isocratic conditions (0.4% (v/v) 2
      mercaptoethanol, 10% (v/v) methanol, pH 2.5, flow rate 0.7 mL min(-1)). ICP-MS
      detection was performed by monitoring the mercury mass to charge ratio of 202.
      The limits of quantification of the method were 11, 6.7, and 12 ng L(-1), for
      inorganic mercury, methyl-mercury and ethyl-mercury, respectively (pre
      concentration factor of 50); whereas, analytical recoveries ranged from 96 to
      106%. The developed method was successfully applied to several seawater samples
      from unpolluted areas.

PMID- 25769900
TI  - Highly Sensitive Droplet Digital PCR Method for Detection of EGFR-Activating
      Mutations in Plasma Cell-Free DNA from Patients with Advanced Non-Small Cell Lung
      Cancer.
AB  - Epidermal growth factor receptor (EGFR) mutation testing in plasma cell-free DNA
      from lung cancer patients is an emerging clinical tool. However, compared with
      tissue testing, the sensitivity of plasma testing is not yet satisfactory because
      of the highly fragmented nature of plasma cell-free DNA, low fraction of tumor
      DNA, and limitations of available detection technologies. We therefore developed
      a highly sensitive and specific droplet digital PCR method for plasma EGFR
      mutation (exon19 deletions and L858R) testing. Plasma from 86 EGFR-tyrosine
      kinase inhibitor-naive lung cancer patients was tested and compared with EGFR
      mutation status of matched tumor tissues tested by amplification refractory
      mutation system. By using EGFR mutation-positive cell DNA, we optimized the
      droplet digital PCR assays to reach 0.04% sensitivity. The plasma testing
      sensitivity and specificity, compared with the matched tumor tissues tested by
      amplification refractory mutation system, were 81.82% (95% CI, 59.72%-94.81%) and
      98.44% (95% CI, 91.60%-99.96%), respectively, for exon19 deletions, with 94.19%
      concordance rate (kappa = 0.840; 95% CI, 0.704-0.976; P < 0.0001), whereas they
      were 80.00% (95% CI, 51.91%-95.67%) and 95.77% (95% CI, 88.14%-99.12%),
      respectively, for L858R, with 93.02% concordance rate (kappa = 0.758; 95% CI,
      0.571-0.945; P < 0.0001). The reported highly sensitive and specific droplet
      digital PCR assays for EGFR mutation detection have potential in clinical blood
      testing. 

PMID- 25769901
TI  - Functional brain imaging in survivors of critical illness: A prospective
      feasibility study and exploration of the association between delirium and brain
      activation patterns.
AB  - PURPOSE: We undertook this pilot prospective cohort investigation to examine the
      feasibility of functional magnetic resonance imaging (fMRI) assessments in
      survivors of critical illness and to analyze potential associations between
      delirium and brain activation patterns observed during a working memory task (N
      back) at hospital discharge and 3-month follow-up. MATERIALS AND METHODS: At
      hospital discharge and 3 months later, fMRI assessed subjects' functional
      activity during an N-back task. Multiple linear regression was used to examine
      associations between duration of delirium and brain activity, and elastic net
      regression was used to assess the relationship between brain activation patterns
      at 3 months and cognitive outcomes at 12 months. RESULTS: Of 47 patients who
      underwent fMRI at discharge, 38 (80%) completed the protocol; of 37 who underwent
      fMRI at 3 months, 34 (91%) completed the protocol. At discharge, the mean (SD)
      percentage of correct responses on the most challenging version (the N2 version)
      of the N-back task was 70.4 (23.2; range of 20-100) compared with 76 (23.4; range
      of 33-100) at 3 months. No association was observed between delirium duration in
      the hospital and brain region activity in any brain region at discharge or 3
      months after adjusting for relevant covariates (P values across all 11 brain
      regions of interest were >.25). CONCLUSIONS: Our data support the feasibility of
      using fMRI in survivors of critical illness at 3-month follow-up but not at
      discharge. In this small study, delirium was not associated with distinct or
      abnormal brain activation patterns, although overall performance on a cognitive
      task of working memory was poorer than observed in other cohorts of individuals
      with medically related executive dysfunction, mild cognitive impairment, and mild
      traumatic brain injury.

PMID- 25769902
TI  - Molecular Diagnosis of Shrimp Allergy: Efficiency of Several Allergens to Predict
      Clinical Reactivity.
AB  - BACKGROUND: The diagnosis of shellfish allergy remains a challenge for
      clinicians. Several shellfish allergens have been characterized and their IgE
      epitopes identified. However, the clinical relevance of this sensitization is
      still not clear. OBJECTIVE: The objective of this study was to identify allergens
      and epitopes associated with clinical reactivity to shrimp. METHODS: Shrimp
      sensitized subjects were recruited and grouped based on the history of shrimp
      allergic reactions and challenge outcome. IgE reactivity to recombinant
      crustacean allergens, and IgE and IgG4 reactivity to peptides were determined.
      Subjects sensitized to dust mites and/or cockroach without shrimp sensitization
      or reported allergic reactions, as well as nonatopic individuals, were used as
      controls. RESULTS: A total of 86 subjects were recruited with a skin prick test
      to shrimp; 74 reported shrimp-allergic reactions, 58 were allergic (38 positive
      double-blind placebo-controlled food challenge and 20 recent anaphylaxis), and 16
      were tolerant. All subjects without a history of reactions had negative
      challenges. The individuals with a positive challenge more frequently recognized
      tropomyosin and sarcoplasmic calcium-binding proteins than those found tolerant
      by the challenge. Especially a sarcoplasmic-calcium-binding-protein positive test
      is very likely to result in a positive challenge, though the frequency of
      recognition is low. Subjects with dust mite and/or cockroach allergy not
      sensitized to shrimp recognized arginine kinase and hemocyanin. Several epitopes
      of these allergens may be important in predicting clinical reactivity.
      CONCLUSION: Tropomyosin and sarcoplasmic-calcium-binding-protein sensitization is
      associated with clinical reactivity to shrimp. Myosin light chain testing may
      help in the diagnosis of clinical reactivity. Arginine kinase and hemocyanin
      appear to be cross-reacting allergens between shrimp and arthropods. Detection of
      IgE to these allergens and some of their epitopes may be better diagnostic tools
      in the routine workup of shrimp allergy.

PMID- 25769903
TI  - Outcome and value of reverse shoulder arthroplasty for treatment of glenohumeral
      osteoarthritis: a matched cohort.
AB  - BACKGROUND: Total shoulder arthroplasty (TSA) is commonly used to treat
      glenohumeral osteoarthritis (GHOA) with an intact rotator cuff. Recently, reverse
      shoulder arthroplasty (RSA) has been used for GHOA patients who are elderly or
      have eccentric glenoid wear. We evaluated patients with GHOA scheduled to have
      TSA but who were changed to RSA because of intraoperative difficulties with the
      glenoid component or instability and compared them with a cohort that underwent
      TSA to determine if the groups had similar outcomes. METHODS: We identified 24
      consecutive GHOA patients who underwent RSA and matched them to 96 patients who
      underwent TSA. Glenoid wear and rotator cuff musculature were assessed with
      preoperative computed tomography scans. Direct hospital costs of the procedure
      were collected. RESULTS: Postoperative American Shoulder and Elbow Surgeons
      score, Simple Shoulder Test score, and range of motion were similar between the 2
      groups. Five TSA patients had radiographic glenoid loosening, whereas no RSA
      patients did. Neither group required a revision. One RSA patient required surgery
      for treatment of a periprosthetic fracture. RSA was $7274 more costly than TSA,
      related mainly to implant cost. CONCLUSIONS: Patients with GHOA who were
      converted intraoperatively to RSA because of improper seating of the glenoid
      trial or persistent posterior subluxation had outcomes comparable to those of a
      similar group of patients in whom TSA was performed. At midterm follow-up, TSA is
      associated with lower cost than RSA. The higher rate of radiographic loosening in
      the TSA group warrants longer follow-up to assess revision costs. In cases in
      which a TSA cannot be performed with confidence, RSA is a reasonable alternative.

PMID- 25769904
TI  - Rocking-horse phenomenon of the glenoid component: the importance of inclination.
AB  - BACKGROUND: Abnormal glenoid version positioning has been recognized as a cause
      of glenoid component failure caused by the rocking horse phenomenon. In contrast,
      the importance of the glenoid inclination has not been investigated. MATERIALS
      AND METHODS: The computed tomography scans of 152 healthy shoulders were
      evaluated. A virtual glenoid component was positioned in 2 different planes: the
      maximum circular plane (MCP) and the inferior circle plane (ICP). The MCP was
      defined by the best fitting circle of the most superior point of the glenoid and
      2 points at the lower glenoid rim. The ICP was defined by the best fitting circle
      on the rim of the inferior quadrants. The inclination of both planes was measured
      as the intersection with the scapular plane. We defined the force vector of the
      rotator force couple and calculated the magnitude of the shear force vector on a
      virtual glenoid component in both planes during glenohumeral abduction. RESULTS:
      The inclination of the component positioned in the MCP averaged 95 degrees 
      (range, 84 degrees -108 degrees ) and for the ICP averaged 111 degrees  (range,
      94 degrees -126 degrees ). A significant reduction in shear forces was calculated
      for the glenoid component in the ICP vs the MCP: 98% reduction in 60 degrees  of
      abduction to 49% reduction in 90 degrees  of abduction. CONCLUSION: Shear forces
      are significantly higher when the glenoid component is positioned in the MCP
      compared with the ICP, and this is more pronounced in early abduction.
      Positioning the glenoid component in the inferior circle might reduce the risk of
      a rocking horse phenomenon.

PMID- 25769905
TI  - Bilateral pulmonary emboli after elective elbow arthroscopy: a case report.

PMID- 25769906
TI  - Shoulder position increases ulnar nerve strain at the elbow of patients with
      cubital tunnel syndrome.
AB  - BACKGROUND: Previous studies have shown that the shoulder internal rotation elbow
      flexion (SIREF) test, which is a modified elbow flexion (EF) test, has
      significantly higher sensitivity than the EF test in patients with cubital tunnel
      syndrome (CubTS). Here, we hypothesized that this increase in sensitivity was due
      to increase in the ulnar nerve strain around the elbow introduced by the
      additional shoulder position. METHODS: Ulnar nerve strain at the elbow was
      intraoperatively measured at both the EF test and SIREF test positions in 20
      patients with CubTS before simple decompression. Statistical analysis was
      performed with the Wilcoxon signed rank test at a confidence level of 99% (P <
      .001). RESULTS: Mean ulnar nerve strain in the EF test position was 18.9% +/-
      12.1%, whereas that in the SIREF test position was 24.7% +/- 14.0%. Ulnar nerve
      strain was higher in the SIREF than in the EF test position in all cases, and the
      difference was significant (mean, 5.8% +/- 0.9%; 95% confidence interval, 3.90%
      7.73%). CONCLUSION: This study indicated that increased sensitivity in the SIREF
      test compared with the EF test was due to the increase in ulnar nerve strain
      around the elbow. To the best of our knowledge, this is the first study showing
      that shoulder position changes the ulnar nerve strain around the elbow in living
      patients with CubTS.

PMID- 25769907
TI  - Evaluation of thymic volume by postmortem computed tomography.
AB  - The thymus is exceedingly sensitive to stress and undergoes abrupt involution as
      a result of exposure to strong stress in early childhood. Therefore, thymic
      involution is often utilized to assess the presence of a stressful environment,
      such as an environment involving child abuse, in forensic medicine. In recent
      years, computed tomography (CT) has been commonly used in the daily practice of
      forensic medicine. We have focused on the thymic volume in postmortem CT images
      to evaluate the presence of a stressful antemortem environment. We calculated the
      thymus volume from postmortem CT images of children under six years old and
      demonstrated that the volume showed a positive correlation with the real weight
      obtained from an autopsy. The evaluation of thymic volume by CT may make it
      possible for us to identify child maltreatment. The most useful feature of this
      application of CT is to be able to demonstrate thymic involution less invasively
      in a surviving victim. 

PMID- 25769908
TI  - An eight year (2005-2013) temporal trend of halogenated organic pollutants in
      fish from the Pearl River Estuary, South China.
AB  - Dichlorodiphenyltrichloroethane and its metabolites (DDTs),
      hexachlorocyclohexanes (HCHs), polychlorinated biphenyls (PCBs), polybrominated
      diphenyl ethers (PBDEs), dechlorane plus (DP), 2,3,5,6-tetrabromo-p-xylene (pTBX)
      and pentabromotoluene (PBT) were measured in baby croaker (Collichthys lucidus)
      and mullet (Osteomugil ophuyseni) collected in 2005 and 2013 from the Pearl River
      Estuary. DDTs, HCHs, PCBs, and PBDEs were detected in two fish species at
      concentrations of 150-8100, 1.4-120, 22-560, 2.2-280 ng/g lipid wt.,
      respectively. The levels of these chemicals were significantly lower in 2013 than
      in 2005. The compositions for DDTs, HCHs, and PBDEs in 2013 differed from those
      in 2005, indicating source changes between the two sampling periods. DP, pTBX and
      PBT were detected at concentrations of ND-130 ng/g lipid wt. No clear temporal
      trends were found for these contaminants. Overall, these results indicated the
      effectiveness of regulations and source controls in substantively reducing inputs
      of these contaminants to the Pearl River Estuary.

PMID- 25769909
TI  - Validation of a Model for Teaching Canine Fundoscopy.
AB  - A validated teaching model for canine fundoscopic examination was developed to
      improve Day One fundoscopy skills while at the same time reducing use of teaching
      dogs. This novel eye model was created from a hollow plastic ball with a cutout
      for the pupil, a suspended 20-diopter lens, and paint and paper simulation of
      relevant eye structures. This eye model was mounted on a wooden stand with canine
      head landmarks useful in performing fundoscopy. Veterinary educators performed
      fundoscopy using this model and completed a survey to establish face and content
      validity. Subsequently, veterinary students were randomly assigned to pre
      laboratory training with or without the use of this teaching model. After
      completion of an ophthalmology laboratory on teaching dogs, student outcome was
      assessed by measuring students' ability to see a symbol inserted on the simulated
      retina in the model. Students also completed a survey regarding their experience
      with the model and the laboratory. Overall, veterinary educators agreed that this
      eye model was well constructed and useful in teaching good fundoscopic technique.
      Student performance of fundoscopy was not negatively impacted by the use of the
      model. This novel canine model shows promise as a teaching and assessment tool
      for fundoscopy. 

PMID- 25769911
TI  - Anti-IL-23A mAb BI 655066 for treatment of moderate-to-severe psoriasis: Safety,
      efficacy, pharmacokinetics, and biomarker results of a single-rising-dose,
      randomized, double-blind, placebo-controlled trial.
AB  - BACKGROUND: IL-23 is associated with plaque psoriasis susceptibility and
      pathogenesis. BI 655066 is a fully human IgG1 mAb specific for the IL-23 p19
      subunit. OBJECTIVE: This first-in-human proof-of-concept study evaluated the
      clinical and biological effects of BI 655066 in patients with moderate-to-severe
      plaque psoriasis. METHODS: We performed a single-rising-dose, multicenter,
      randomized, double-blind, placebo-controlled, within-dose cohort phase I trial.
      Patients received 0.01, 0.05, 0.25, 1, 3, or 5 mg/kg BI 655066 intravenously,
      0.25 or 1 mg/kg BI 655066 subcutaneously, or matched placebo. The primary
      objective was safety evaluation. RESULTS: Thirty-nine patients received single
      dose BI 655066 intravenously (n = 18) or subcutaneously (n = 13) or placebo (n =
      8). Adverse events were reported with similar frequency in the BI 655066 and
      placebo groups. Four serious adverse events (not considered treatment related)
      were reported among BI 655066-treated patients. BI 655066 was associated with
      clinical improvement from week 2 and maintained for up to 66 weeks after
      treatment. At week 12, 75%, 90%, and 100% decreases in the Psoriasis Area and
      Severity Index were achieved by 87%, 58%, and 16% of BI 655066-treated patients
      (any dose), respectively, versus none receiving placebo. BI 655066 treatment
      resulted in reduced expression of lesional skin genes associated with IL-23/IL-17
      signaling pathways and normalization of psoriatic lesion gene expression profiles
      to a profile approaching that of nonlesional skin. Significant correlation
      between treatment-associated molecular changes and psoriasis area and severity
      index improvement was observed (r = 0.73, P = 2 * 10(-6)). CONCLUSIONS: BI 655066
      was well tolerated and associated with rapid, substantial, and durable clinical
      improvement in patients with moderate-to-severe psoriasis, supporting a central
      role for IL-23 in psoriasis pathogenesis.

PMID- 25769912
TI  - Childhood allergic asthma is associated with increased IL-13 and FOXP3 histone
      acetylation.

PMID- 25769910
TI  - DNA methylation and childhood asthma in the inner city.
AB  - BACKGROUND: Epigenetic marks are heritable, influenced by the environment, direct
      the maturation of T lymphocytes, and in mice enhance the development of allergic
      airway disease. Thus it is important to define epigenetic alterations in
      asthmatic populations. OBJECTIVE: We hypothesize that epigenetic alterations in
      circulating PBMCs are associated with allergic asthma. METHODS: We compared DNA
      methylation patterns and gene expression in inner-city children with persistent
      atopic asthma versus healthy control subjects by using DNA and RNA from PBMCs.
      Results were validated in an independent population of asthmatic patients.
      RESULTS: Comparing asthmatic patients (n = 97) with control subjects (n = 97), we
      identified 81 regions that were differentially methylated. Several immune genes
      were hypomethylated in asthma, including IL13, RUNX3, and specific genes relevant
      to T lymphocytes (TIGIT). Among asthmatic patients, 11 differentially methylated
      regions were associated with higher serum IgE concentrations, and 16 were
      associated with percent predicted FEV1. Hypomethylated and hypermethylated
      regions were associated with increased and decreased gene expression,
      respectively (P < 6 * 10(-12) for asthma and P < .01 for IgE). We further
      explored the relationship between DNA methylation and gene expression using an
      integrative analysis and identified additional candidates relevant to asthma (IL4
      and ST2). Methylation marks involved in T-cell maturation (RUNX3), TH2 immunity
      (IL4), and oxidative stress (catalase) were validated in an independent asthmatic
      cohort of children living in the inner city. CONCLUSIONS: Our results demonstrate
      that DNA methylation marks in specific gene loci are associated with asthma and
      suggest that epigenetic changes might play a role in establishing the immune
      phenotype associated with asthma.

PMID- 25769913
TI  - Gut microbiome variations during hematopoietic stem cell transplant in severe
      combined immunodeficiency.

PMID- 25769914
TI  - Antibody conjugates bispecific for intercellular adhesion molecule 1 and allergen
      prevent migration of allergens through respiratory epithelial cell layers.

PMID- 25769915
TI  - Molecular characterization of CD9 and CD63, two tetraspanin family members
      expressed in trout B lymphocytes.
AB  - Tetraspanins are a family of membrane-organizing proteins, characterized by the
      presence of four highly conserved transmembrane regions that mediate diverse
      physiological functions. In the current study, we have identified two novel
      tetraspanin members in rainbow trout (Oncorhynchus mykiss), homologs to mammalian
      CD9 and CD63. Both genes were expressed in muscle, skin, gills, hindgut, gonad,
      liver, spleen, head kidney, thymus and peripheral blood leukocytes. Throughout
      the early life cycle stages, CD9 mRNA levels significantly increased after first
      feeding, whereas CD63 transcription remained constant during all the
      developmental stages analyzed. In response to an experimental bath infection with
      viral hemorrhagic septicemia virus (VHSV), CD9 transcription was down-regulated
      in the gills, while CD63 mRNA levels were down-regulated in the head kidney.
      Instead, when the virus was intraperitoneally injected, the transcription of both
      genes was significantly up-regulated in peritoneal cells at several days post
      infection. Additionally, both genes were transcriptionally up-regulated in the
      muscle of trout injected with a VHSV DNA vaccine. To gain insight on the relation
      of these tetraspanins with B cell activity we determined their constitutive
      expression in naive IgM(+) populations from different sources and observed that
      both molecules were being transcribed by IgM(+) cells in different tissues.
      Furthermore, CD9 transcription was significantly down-regulated in splenic IgM(+)
      cells in response to in vitro VHSV exposure. Our results provide insights on the
      potential role of these tetraspanins on teleost B cell and antiviral immunity. 

PMID- 25769916
TI  - The combined effect of genetic polymorphisms and clinical parameters on treatment
      outcome in treatment-resistant depression.
AB  - For over a decade, the European Group for the Study of Resistant Depression
      (GSRD) has examined single nucleotide polymorphisms (SNP) and clinical parameters
      in regard to treatment outcome. However, an interaction based model combining
      these factors has not been established yet. Regarding the low effect of
      individual SNPs, a model investigating the interactive role of SNPs and clinical
      variables in treatment-resistant depression (TRD) seems auspicious. Thus 225
      patients featured in previous work of the GSRD were enrolled in this
      investigation. According to data availability and previous positive results, 12
      SNPs in HTR2A, COMT, ST8SIA2, PPP3CC and BDNF as well as 8 clinical variables
      featured in other GSRD studies were chosen for this investigation. Random forests
      algorithm were used for variable shrinkage and k-means clustering for surfacing
      variable characteristics determining treatment outcome. Using these machine
      learning and clustering algorithms, we detected a set of 3 SNPs and a clinical
      variable that was significantly associated with treatment response. About 62% of
      patients exhibiting the allelic combination of GG-GG-TT for rs6265, rs7430 and
      rs6313 of the BDNF, PPP3CC and HTR2A genes, respectively, and without melancholia
      showed a HAM-D decline under 17 compared to about 34% of the whole study sample.
      Our random forests prediction model for treatment outcome showed that combining
      clinical and genetic variables gradually increased the prediction performance
      recognizing correctly 25% of responders using all 4 factors. Thus, we could
      confirm our previous findings and furthermore show the strength of an interaction
      based model combining statistical algorithms in identifying and operating
      treatment predictors. 

PMID- 25769917
TI  - Clozapine use in childhood and adolescent schizophrenia: A nationwide population
      based study.
AB  - Early onset schizophrenia (EOS) begins in childhood or adolescence. EOS is
      associated with poor treatment response and may benefit from timely use of
      clozapine. This study aimed to identify the predictors of clozapine use in EOS
      and characterize the clinical profile and outcome of clozapine-treated youths
      with schizophrenia. We conducted a nationwide population-based study using linked
      data from Danish medical registries. We examined all incident cases of EOS (i.e.,
      cases diagnosed prior to their 18th birthday) between December 31st 1994 and
      December 31st 2006 and characterized their demographic, clinical and treatment
      profiles. We then used multivariable cox proportional hazard models to identify
      predictors of clozapine treatment in this patient population. We identified 662
      EOS cases (1.9% of all schizophrenia cases), of whom 108 (17.6%) had commenced
      clozapine by December 31st 2008. Patients had on average 3 antipsychotic trials
      prior to clozapine initiation. The mean interval between first antipsychotic
      treatment and clozapine initiation was 3.2 (2.9) years. Older age at diagnosis of
      schizophrenia [HR=1.2, 95% CI (1.05-1.4), p=0.01], family history of
      schizophrenia [HR=2.1, 95% CI (1.1-3.04), p=0.02] and attempted suicide [HR=1.8,
      95% CI (1.1-3.04), p=0.02] emerged as significant predictors of clozapine use.
      The majority of patients (n=96, 88.8%) prescribed clozapine appeared to have a
      favorable clinical response as indicated by continued prescription redemption and
      improved occupational outcomes. Our findings support current recommendations for
      the timely use of clozapine in EOS. 

PMID- 25769919
TI  - Identification of a negative regulatory role for spi-C in the murine B cell
      lineage.
AB  - Spi-C is an E26 transformation-specific family transcription factor that is
      highly related to PU.1 and Spi-B. Spi-C is expressed in developing B cells, but
      its function in B cell development and function is not well characterized. To
      determine whether Spi-C functions as a negative regulator of Spi-B (encoded by
      Spib), mice were generated that were germline knockout for Spib and heterozygous
      for Spic (Spib(-/-)Spic(+/-)). Interestingly, loss of one Spic allele
      substantially rescued B cell frequencies and absolute numbers in Spib(-/-) mouse
      spleens. Spib(-/-)Spic(+/-) B cells had restored proliferation compared with
      Spib(-/-) B cells in response to anti-IgM or LPS stimulation. Investigation of a
      potential mechanism for the Spib(-/-)Spic(+/-) phenotype revealed that steady
      state levels of Nfkb1, encoding p50, were elevated in Spib(-/-)Spic(+/-) B cells
      compared with Spib(-/-) B cells. Spi-B was shown to directly activate the Nfkb1
      gene, whereas Spi-C was shown to repress this gene. These results indicate a
      novel role for Spi-C as a negative regulator of B cell development and function. 

PMID- 25769918
TI  - Unbiased modifier screen reveals that signal strength determines the regulatory
      role murine TLR9 plays in autoantibody production.
AB  - The autoimmune disease systemic lupus erythematosus has a complex environmental
      and multifactorial genetic basis. Genome-wide association studies have recently
      identified numerous disease-associated polymorphisms, but it remains unclear in
      which cells and during which step of pathogenesis specific polymorphisms interact
      to cause disease. Using a mouse model in which the same activating mutation
      (CD45E613R) causes distinct genetic background-dependent disease phenotypes, we
      performed a screen for genetic modifiers of autoreactivity between anti-nuclear
      Ab (ANA)-resistant CD45E613R.B6 and ANA-permissive CD45E613R.BALB/c mice. Within
      a novel autoreactivity-associated locus on chromosome 9, we identify a putative
      modifier, TLR9. Validating a role for TLR9 in modifying autoreactivity in the
      context of the CD45E613R mutation, manipulation of TLR9 gene dosage eliminates
      ANA in CD45E613R.BALB/c mice, but confoundingly permits ANA in CD45E613R.B6 mice.
      We demonstrate that sensitivity to ANA is modulated by strength of TLR9 signal,
      because stronger TLR9(B6) signals, but not weaker TLR9(BALB/c) signals,
      negatively regulate CD45E613R B cell development during competitive
      reconstitution at the central tolerance checkpoint. Our results identify a novel
      autoreactivity-associated locus and validate Tlr9 as a candidate gene within the
      locus. We further demonstrate a novel role for TLR9 signal strength in central
      tolerance, providing insight into the interplay of disease-associated
      polymorphisms at a discrete step of systemic lupus erythematosus pathogenesis. 

PMID- 25769920
TI  - IgM and IgA rheumatoid factors purified from rheumatoid arthritis sera boost the
      Fc receptor- and complement-dependent effector functions of the disease-specific
      anti-citrullinated protein autoantibodies.
AB  - Rheumatoid factors (RF) and the disease-specific anti-citrullinated protein
      autoantibodies (ACPA) coexist in the joints of rheumatoid arthritis (RA) patients
      where they probably contribute to synovitis. We investigated the influence of IgM
      and IgA RF on the FcR- and complement-dependent effects of ACPA immune complexes
      (ACPA-IC). When stimulated by ACPA-IC formed in the presence of IgM RF or IgA RF
      fractions purified from RA serum pools, M-CSF-generated macrophages skewed their
      cytokine response toward inflammation, with increases in the TNF-alpha/IL-10
      ratio and in IL-6 and IL-8 secretion, and decreases in the IL-1Ra/IL-1beta ratio.
      In the IgM RF-mediated amplification of the inflammatory response of macrophages,
      the participation of an IgM receptor was excluded, notably by showing that they
      did not express any established receptor for IgM. Rather, this amplification
      depended on the IgM RF-mediated recruitment of more IgG into the ACPA-IC.
      However, the macrophages expressed FcalphaRI and blocking its interaction with
      IgA inhibited the IgA RF-mediated amplification of TNF-alpha secretion induced by
      ACPA-IC, showing its major implication in the effects of RF of the IgA class. LPS
      further amplified the TNF-alpha response of macrophages to RF-containing ACPA-IC.
      Lastly, the presence of IgM or IgA RF increased the capacity of ACPA-IC to
      activate the complement cascade. Therefore, specifically using autoantibodies
      from RA patients, the strong FcR-mediated or complement-dependent pathogenic
      potential of IC including both ACPA and IgM or IgA RF was established.
      Simultaneous FcR triggering by these RF-containing ACPA-IC and TLR4 ligation
      possibly makes a major contribution to RA synovitis. 

PMID- 25769921
TI  - The C-terminal disulfide bonds of Helicobacter pylori GroES are critical for IL-8
      secretion via the TLR4-dependent pathway in gastric epithelial cells.
AB  - Helicobacter pylori GroES (HpGroES), a potent immunogen, is a secreted virulence
      factor that stimulates production of proinflammatory cytokines and may contribute
      to gastric carcinogenesis. HpGroES is larger than other bacterial orthologs
      because of an additional C-terminal region, known as domain B. We found that the
      HpGroES-induced IL-8 release by human gastric epithelial cells was dependent on
      activation of the MAPK and NF-kappaB pathways. HpGroES lacking domain B was
      unable to induce IL-8 release. Additionally, a TLR4 inhibitor significantly
      inhibited IL-8 secretion and reduced HpGroES-induced activation of MAPKs.
      Furthermore, HpGroES-induced IL-8 release by primary gastric epithelial cells
      from TLR4(-/-) mice was significantly lower than from wild-type mice. We also
      found that HpGroES bound to TLR4 in cell lysates and colocalized with TLR4 on the
      cell membrane only when domain B was present. We then constructed two deletion
      mutants lacking C-terminal regions and mutants with point mutations of two of the
      four cysteine residues, C111 and C112, in domain B and found that the deletion
      mutants and a double mutant lacking the C94-C111 and C95-C112 disulfide bonds
      were unable to interact with TLR4 or induce IL-8 release. We conclude that
      HpGroES, in which a unique conformational structure, domain B, is generated by
      these two disulfide bonds, induces IL-8 secretion via a TLR4-dependent mechanism.

PMID- 25769923
TI  - Glomerulopathy induced by immunization with a peptide derived from the
      goodpasture antigen alpha3IV-NC1.
AB  - Mouse experimental autoimmune glomerulonephritis, a model of human antiglomerular
      basement membrane disease, depends on both Ab and T cell responses to the
      Goodpasture Ag noncollagenous domain 1 of the alpha3-chain of type IV collagen
      (alpha3IV-NC1). The aim of our study was to further characterize the T cell
      mediated immune response. Repeated immunization with mouse alpha3IV-NC1 caused
      fatal glomerulonephritis in DBA/1 mice. Although two immunizations were
      sufficient to generate high alpha3IV-NC1-specific IgG titers, Ab and complement
      deposition along the glomerular basement membranes, and a nephrotic syndrome, two
      additional immunizations were needed to induce a necrotizing/crescentic
      glomerulonephritis. Ten days after the first immunization, alpha3IV-NC1-specific
      CD4(+) cells producing TNF-alpha, IFN-gamma, or IL-17A were detected in the
      spleen. With the emergence of necrotizing/crescentic glomerulonephritis, ~0.15%
      of renal CD4(+) cells were specific for alpha3IV-NC1. Using peptides spanning the
      whole alpha3IV-NC1 domain, three immunodominant T cell epitopes were identified.
      Immunization with these peptides did not lead to clinical signs of experimental
      autoimmune glomerulonephritis or necrotizing/crescentic glomerulonephritis.
      However, mice immunized with one of the peptides (STVKAGDLEKIISRC) developed
      circulating Abs against mouse alpha3IV-NC1 first detected at 8 wk, and 50% of the
      mice showed mild proteinuria at 18-24 wk due to membranous glomerulopathy. Taken
      together, our results suggest that autoreactive T cells are able to induce the
      formation of pathologic autoantibodies. The quality and quantity of alpha3IV-NC1
      specific Ab and T cell responses are critical for the phenotype of the
      glomerulonephritis. 

PMID- 25769922
TI  - Complement receptor C5aR1/CD88 and dipeptidyl peptidase-4/CD26 define distinct
      hematopoietic lineages of dendritic cells.
AB  - Differential display of the integrins CD103 and CD11b are widely used to
      distinguish two major dendritic cell (DC) subsets in nonlymphoid tissues.
      CD103(+) DCs arise from FLT3-dependent DC precursors (preDCs), whereas CD11b(hi)
      DCs can arise either from preDCs or FLT3-independent monocytes. Functional
      characterization of these two lineages of CD11b(hi) DCs has been hindered by the
      lack of a widely applicable method to distinguish between them. We performed gene
      expression analysis of fractionated lung DCs from C57BL/6 mice and found that
      monocyte-derived DCs (moDCs), including CD11b(hi)Ly-6C(lo) tissue-resident and
      CD11b(hi)Ly-6C(hi) inflammatory moDCs, express the complement 5a receptor 1/CD88,
      whereas preDC-derived conventional DCs (cDCs), including CD103(+) and CD11b(hi)
      cDCs, express dipeptidyl peptidase-4/CD26. Flow cytometric analysis of multiple
      organs, including the kidney, liver, lung, lymph nodes, small intestine, and
      spleen, confirmed that reciprocal display of CD88 and CD26 can reliably
      distinguish FLT3-independent moDCs from FLT3-dependent cDCs in C57BL/6 mice.
      Similar results were obtained when DCs from BALB/c mice were analyzed. Using this
      novel approach to study DCs in mediastinal lymph nodes, we observed that most
      blood-derived lymph node-resident DCs, as well as tissue-derived migratory DCs,
      are cDCs. Furthermore, cDCs, but not moDCs, stimulated naive T cell
      proliferation. We anticipate that the use of Abs against CD88 and CD26 to
      distinguish moDCs and cDCs in multiple organs and mouse strains will facilitate
      studies aimed at assigning specific functions to distinct DC lineages in immune
      responses. 

PMID- 25769924
TI  - Phenotypic variation in Aicardi-Goutieres syndrome explained by cell-specific IFN
      stimulated gene response and cytokine release.
AB  - Aicardi-Goutieres syndrome (AGS) is a monogenic inflammatory encephalopathy
      caused by mutations in TREX1, RNASEH2A, RNASEH2B, RNASEH2C, SAMHD1, ADAR1, or
      MDA5. Mutations in those genes affect normal RNA/DNA intracellular metabolism and
      detection, triggering an autoimmune response with an increase in cerebral IFN
      alpha production by astrocytes. Microangiopathy and vascular disease also
      contribute to the neuropathology in AGS. In this study, we report that AGS gene
      silencing of TREX1, SAMHD1, RNASEH2A, and ADAR1 by short hairpin RNAs in human
      neural stem cell-derived astrocytes, human primary astrocytes, and brain-derived
      endothelial cells leads to an antiviral status of these cells compared with
      nontarget short hairpin RNA-treated cells. We observed a distinct activation of
      the IFN-stimulated gene signature with a substantial increase in the release of
      proinflammatory cytokines (IL-6) and chemokines (CXCL10 and CCL5). A differential
      impact of AGS gene silencing was noted; silencing TREX1 gave rise to the most
      dramatic in both cell types. Our findings fit well with the observation that
      patients carrying mutations in TREX1 experience an earlier onset and fatal
      outcome. We provide in the present study, to our knowledge for the first time,
      insight into how astrocytic and endothelial activation of antiviral status may
      differentially lead to cerebral pathology, suggesting a rational link between
      proinflammatory mediators and disease severity in AGS. 

PMID- 25769925
TI  - Cutting edge: identification of autoreactive CD4+ and CD8+ T cell subsets
      resistant to PD-1 pathway blockade.
AB  - Programmed death-1 (PD-1) promotes T cell tolerance. Despite therapeutically
      targeting this pathway for chronic infections and tumors, little is known about
      how different T cell subsets are affected during blockade. We examined PD-1/PD
      ligand 1 (PD-L1) regulation of self-antigen-specific CD4 and CD8 T cells in
      autoimmune-susceptible models. PD-L1 blockade increased insulin-specific effector
      CD4 T cells in type 1 diabetes. However, anergic islet-specific CD4 T cells were
      resistant to PD-L1 blockade. Additionally, PD-L1 was critical for induction, but
      not maintenance, of CD8 T cell intestinal tolerance. PD-L1 blockade enhanced
      functionality of effector T cells, whereas established tolerant or anergic T
      cells were not dependent on PD-1/PD-L1 signaling to remain unresponsive. This
      highlights the existence of Ag-experienced T cell subsets that do not rely on PD
      1/PD-L1 regulation. These findings illustrate how positive treatment outcomes and
      autoimmunity development during PD-1/PD-L1 inhibition are linked to the
      differentiation state of a T cell. 

PMID- 25769927
TI  - Mesenchymal stem/stromal cells protect against autoimmunity via CCL2-dependent
      recruitment of myeloid-derived suppressor cells.
AB  - Exogenously administered mesenchymal stem/stromal cells (MSCs) suppress
      autoimmunity despite transient engraftment. However, the mechanism is unclear. In
      this study, we report a novel mechanism by which MSCs modulate the immune system
      by recruiting myeloid-derived suppressor cells in a mouse model of experimental
      autoimmune uveitis (EAU). Intravenous infusion of MSCs blocked EAU development
      and reduced Th1 and Th17 responses. Time course analysis revealed an increase of
      MHC class II(lo)Ly6G(-)Ly6C(hi)CD11b(+) cells in draining lymph nodes by MSCs.
      These Ly6C(hi)CD11b(+) cells suppressed CD4(+) cell proliferation and Th1/Th17
      differentiation and induced CD4(+) cell apoptosis. Adoptive transfer of
      Ly6C(hi)CD11b(+) cells ameliorated EAU, whereas depletion of Ly6C(hi)CD11b(+)
      cells abrogated the effects of MSCs. 1.8% of MSCs were present in draining lymph
      nodes 1 d after infusion, and MSCs with CCL2 knockdown did not increase MHC class
      II(lo)Ly6G(-)Ly6C(hi)CD11b(+) cells and failed to attenuate EAU. Therefore, our
      findings demonstrate that MSCs suppress autoimmunity by recruiting myeloid
      derived suppressor cells into sites of inflammation in a CCL2-dependent manner. 

PMID- 25769926
TI  - Estradiol inhibits Th17 cell differentiation through inhibition of RORgammaT
      transcription by recruiting the ERalpha/REA complex to estrogen response elements
      of the RORgammaT promoter.
AB  - The symptoms of vaginal candidiasis exacerbate in the second half of the
      menstrual cycle in premenopausal women when the serum estradiol level is
      elevated. Estradiol has been shown to inhibit Th17 differentiation and production
      of antifungal IL-17 cytokines. However, little is known about the mechanisms. In
      the present study, we used mouse splenocytes and found that estradiol inhibited
      Th17 differentiation through downregulation of Rorgammat mRNA and protein
      expression. Estradiol activated estrogen receptor (ER)alpha to recruit repressor
      of estrogen receptor activity (REA) and form the ERalpha/REA complex. This
      complex bound to three estrogen response element (ERE) half-sites on the
      Rorgammat promoter region to suppress Rorgammat expression. Estradiol induced Rea
      mRNA and protein expression in mouse splenocytes. Using Rea small interfering RNA
      to knock down Rea expression enhanced Rorgammat expression and Th17
      differentiation. Alternatively, histone deacetylase 1 and 2 bound to the three
      ERE half-sites, independent of estradiol. Histone deacetylase inhibitor MS-275
      dose- and time-dependently increased Rorgammat expression and subsequently
      enhanced Th17 differentiation. In 15 healthy premenopausal women, high serum
      estradiol levels are correlated with low RORgammaT mRNA levels and high REA mRNA
      levels in the vaginal lavage. These results demonstrate that estradiol
      upregulates REA expression and recruits REA via ERalpha to the EREs on the
      RORgammaT promoter region, thus inhibiting RORgammaT expression and Th17
      differentiation. This study suggests that the estradiol/ERalpha/REA axis may be a
      feasible target in the management of recurrent vaginal candidiasis. 

PMID- 25769929
TI  - Modular organization of the head retraction responses elicited by electrical
      painful stimulation of the facial skin in humans.
AB  - OBJECTIVE: To explore whether the trigeminocervical reflexes (TCRs) show a reflex
      receptive field organization in the brainstem. METHODS: The facial skin of 16
      healthy subjects was electrically stimulated at nine sites reflecting the
      distribution of the three branches of the trigeminal nerve. The reflex-evoked EMG
      responses were measured bilaterally from the neck muscles and the head and neck
      kinematic reactions were detected. RESULTS: TCRs are site dependent. There was a
      vertical gradient in the magnitude of the reflex responses. EMG and kinematic
      reflexes were larger when evoked from ophthalmic and maxillary sites than from
      mandibular ones. The reflex responses exhibited a crossed right-left behavior.
      Stimulation of the lateral sites evoked larger reflex responses in the
      contralateral trapezium muscle as well as head rotation and neck bending away
      from the stimulated side. CONCLUSION: This modular arrangement of the TCRs seems
      to be related to withdrawal strategies aimed at protecting the face from
      injuries, in accordance with the functional role that each group of muscles plays
      in head and neck motion. SIGNIFICANCE: It is likely that the CNS may exploit the
      neck muscle synergies revealed by the painful stimulation of the skin face in
      order to control the head and neck movements.

PMID- 25769928
TI  - Perturbed T cell IL-7 receptor signaling in chronic Chagas disease.
AB  - We have previously demonstrated that immune responses in subjects with chronic
      Trypanosoma cruzi infection display features common to other persistent
      infections with signs of T cell exhaustion. Alterations in cytokine receptor
      signal transduction have emerged as one of the cell-intrinsic mechanisms of T
      cell exhaustion. In this study, we performed an analysis of the expression of IL
      7R components (CD127 and CD132) on CD4(+) and CD8(+) T cells and evaluated IL-7
      dependent signaling events in patients at different clinical stages of chronic
      chagasic heart disease. Subjects with no signs of cardiac disease showed a
      decrease in CD127(+)CD132(+) cells and a reciprocal gain of CD127(-)CD132(+) in
      CD8(+) and CD4(+) T cells compared with either patients exhibiting heart
      enlargement or uninfected controls. T. cruzi infection, in vitro, was able to
      stimulate the downregulation of CD127 and the upregulation of CD132 on T cells.
      IL-7-induced phosphorylation of STAT5 as well as Bcl-2 and CD25 expression were
      lower in T. cruzi-infected subjects compared with uninfected controls. The serum
      levels of IL-7 were also increased in chronic chagasic patients. The present
      study highlights perturbed IL-7/IL-7R T cell signaling through STAT5 as a
      potential mechanism of T cell exhaustion in chronic T. cruzi infection. 

PMID- 25769930
TI  - Safety and efficacy of the minilaparotomy for myomectomy: a systematic review and
      meta-analysis of randomized and non-randomized controlled trials.
AB  - Myomectomy is the most frequent reproductive surgery to preserve, improve
      fertility, or both. The present study was designed to assess the safety and
      efficacy of minilaparotomy for myomectomy through a systematic review of
      randomized and non-randomized controlled trials with a meta-analysis. All
      available studies comparing minilaparotomy myomectomy with laparotomy, other
      minimally invasive surgeries, or both, were included. Available surgical and
      reproductive data were extrapolated, and a qualitative and quantitative analysis
      was carried out. Fourteen studies were included in the final analysis for an
      overall sample of 2151 patients. A total of 1139 patients were treated with
      minilaparotomy, whereas 239 and 773 patients were treated, respectively, with the
      laparotomy or laparoscopy. Only two studies comparing minilaparotomy with
      laparoscopy assessed the reproductive outcomes, and their data synthesis did not
      demonstrate significant difference between the two surgical techniques. Specific
      surgical end-points differed significantly between minilaparotomy and laparotomy
      or laparoscopy, even if those differences were not clinically relevant. In
      conclusion, current data do not permit a definite conclusion to be drawn. Further
      studies are needed to clarify the risk-benefit ratio of the minilaparotomy
      compared with the other minimally invasive surgical procedures for myomectomy to
      provide clinical recommendations with strong scientific evidence. 

PMID- 25769932
TI  - Pathogenesis of innate immunity and adaptive immunity in the mouse model of
      experimental autoimmune uveitis.
AB  - Experimental autoimmune uveitis, a well-established model for human uveitis, is
      similar to human uveitis in many pathological features. Studies concerning the
      mechanisms of experimental autoimmune uveitis would cast a light on the
      pathogenesis of human uveitis as well as the search for more effective
      therapeutic agents. The cellular components of innate immunity include natural
      killer cells, gamma delta T lymphocytes, antigen-presenting dendritic cells,
      phagocytic macrophages, and granulocytes. It is believed that T cells are central
      in the generation of human uveitis. It has already become clear that CD4(+)
      effecter cells that predominantly produce interleukin-17 (the so-called Th17
      cells) may play an important role in uveitis. In addition, the occurrence and
      recurrence of uveitis depends on a complex interplay between the elements of
      innate and adaptive immunity. 

PMID- 25769931
TI  - Alterations in blood leukocytes of G551D-bearing cystic fibrosis patients
      undergoing treatment with ivacaftor.
AB  - BACKGROUND: Ivacaftor improves clinical outcome by potentiation of mutant G551D
      CFTR. Due to the presence of CFTR in monocytes and polymorphonuclear neutrophils
      (PMNs), we hypothesized that ivacaftor may impact leukocyte activation. METHODS:
      We examined blood leukocytes from G551D CF subjects prior to and at one and six
      months after receiving ivacaftor. Blood leukocytes from ivacaftor-naive G551D,
      F508del, and healthy controls were also treated with ivacaftor ex vivo to assess
      mutation-specific effects. RESULTS: Compared to healthy controls, G551D CF
      subjects had significantly higher expression of active CD11b on PMNs and of CD63
      on monocytes, which were normalized by in vivo ivacaftor treatment. Ex vivo
      exposure to ivacaftor of blood cells from G551D, but not F508del and healthy
      subjects, resulted in changes in CXCR2 and CD16 expression on PMNs. CONCLUSIONS:
      In vivo and ex vivo exposure of G551D CF leukocytes to ivacaftor resulted in an
      altered activation profile, suggesting mutation-specific leukocyte modulation.

PMID- 25769933
TI  - Measurement of peritoneal fluid urea nitrogen and creatinine levels is useful to
      detect iatrogenic urinary tract leakage in colorectal surgery.
AB  - BACKGROUND: Increased peritoneal drainage after colorectal surgery is a common
      problem. Measurement of peritoneal fluid urea nitrogen (UN) and creatinine (Cr)
      is a diagnostic tool to detect the urinary tract leakage (UTL). We evaluated its
      application in colorectal surgery. METHODS: We conducted a retrospective chart
      review study. We enrolled patients with iatrogenic UTL, and measured their UN and
      Cr levels in peritoneal fluid and compared them with those in blood and urine.
      Meanwhile, we assigned patients without UTL to a control group and compared
      clinical parameters of both groups. RESULTS: Twenty-three patients with
      iatrogenic UTL were recruited. The overall incidence was 0.5%. UN level in
      peritoneal fluid (322 +/- 56 mg/dL) was significantly higher than that in blood
      (18.7 +/- 4.0 mg/dL, p < 0.001); Cr level in peritoneal fluid (69.7 +/- 14.3
      mg/dL) was also significantly higher than that in blood (1.5 +/- 0.5 mg/dL, p <
      0.001). UN level in peritoneal fluid was significantly higher in the iatrogenic
      UTL group than in the control group (322 mL/dL vs. 9.3 mL/dL, p < 0.001); Cr
      level in peritoneal fluid was also significantly higher (69.7 mg/dL vs. 0.98
      mg/dL, p < 0.001). CONCLUSION: When increased peritoneal drainage is found
      postoperatively in colorectal surgery, measurement of UN and Cr levels in
      peritoneal fluid can be a useful diagnostic tool to determine intraperitoneal
      iatrogenic UTL.

PMID- 25769934
TI  - Molecular mechanisms of circulatory dysfunction in cirrhotic portal hypertension.
AB  - Acute or chronic insults to the liver are usually followed by a tissue repairing
      process. Unfortunately, this action, in most cases, is not effective enough to
      restore the normal hepatic structure and function. Instead, fibrogenesis and
      regenerative nodules formation ensue, which are relatively nonfunctioning. The
      common final stage of the process is liver cirrhosis with increased intrahepatic
      resistance to portal venous blood flow. Throughout the entire course, the
      extrahepatic circulatory dysfunction, including increased splanchnic blood flow,
      elevated portal venous blood flow and pressure, decreased splanchnic and
      peripheral vascular resistance, tachycardia, and increased cardiac output, are
      noted and denoted as portal hypertension with hyperdynamic circulatory
      dysfunction. When such a condition is established, patients may suffer from fatal
      complications such as gastroesophageal variceal hemorrhage, hepatic
      encephalopathy, or hepatorenal syndrome. The cause of such a circulatory
      dysfunction is not fully elucidated. Nevertheless, clarification of the
      pathophysiology definitely contributes to the control of portal hypertension
      related complications. Herein, the molecular mechanism of this intriguing
      disaster is reviewed and discussed. 

PMID- 25769935
TI  - IAPs and cell migration.
AB  - Inhibitors of apoptosis (IAPs) constitute a family of cell signaling regulators
      controlling several fundamental biological processes such as innate immunity,
      inflammation, cell death, cell proliferation, and cell differentiation.
      Increasing evidence from in vivo and in vitro studies indicate a function for
      IAPs in the modulation of invasive and migratory properties of cells. Here, we
      present and discuss the mechanisms whereby IAPs can control cell migration. 

PMID- 25769936
TI  - Stress as a mediator between work-family conflict and psychological health among
      the nursing staff: Moderating role of emotional intelligence.
AB  - The study examined the extent to which work-family conflicts cause stress among
      nursing staff and its subsequent impact on their psychological health. It also
      examined if the emotional intelligence level of the nursing staff acted as a
      moderator between their level of stress and psychological health. A survey was
      carried out on 693 nursing staff associated with 33 healthcare institutions in
      Uttarakhand, India. A hierarchical multiple regression analysis was carried out
      to understand the relationships shared by independent (work-family conflicts) and
      dependent (psychological health) constructs with the mediator (stress) as well as
      the moderator (emotional intelligence). The results revealed that stress acted as
      a mediator between work-family conflict of the nursing staff and their
      psychological health. However, their emotional intelligence level acted as a
      moderator between their stress level and psychological health. To conclude, the
      crucial roles of emotional intelligence in controlling the impact of stress on
      psychological health along with the practical as well as theoretical implications
      are also discussed. 

PMID- 25769937
TI  - Many readmissions of patients with severe sepsis for other conditions could be
      prevented, US study finds.

PMID- 25769938
TI  - Managing information well: Toward an ontology-driven informatics platform for
      data sharing and secondary use in epilepsy self-management research centers.
AB  - Epilepsy is a chronic neurological condition that requires active self-management
      to reduce personal and population burden. The Managing Epilepsy Well Network,
      funded by the US Centers for Disease Control and Prevention, conducts research on
      epilepsy self-management. There is an urgent need to develop an integrated
      informatics platform to maximize the secondary use of existing Managing Epilepsy
      Well Network data. We have implemented multiple steps to develop an informatics
      platform, including: (a) a survey of existing outcome data, (b) identification of
      common data elements, and (c) an integrated database using an epilepsy domain
      ontology to reconcile data heterogeneity. The informatics platform enables
      assessment of epilepsy self-management samples by site and in aggregate to
      support data interpretations for clinical care and ongoing epilepsy self
      management research. The Managing Epilepsy Well informatics platform is expected
      to help advance epilepsy self-management, improve health outcomes, and has
      potential application in other thematic research networks.

PMID- 25769939
TI  - Emergency department rapid medical assessment: overall effect and mechanistic
      considerations.
AB  - BACKGROUND: Although the use of a physician and nurse team at triage has been
      shown to improve emergency department (ED) throughput, the mechanism(s) by which
      these improvements occur is less clear. OBJECTIVES: 1) To describe the effect of
      a Rapid Medical Assessment (RMA) team on ED length of stay (LOS) and rate of left
      without being seen (LWBS); 2) To estimate the effect of RMA on different groups
      of patients. METHODS: For Objective 1, we compared LOS and LWBS on dates when we
      utilized RMA to comparable dates when we did not. For Objective 2, we utilized
      patient logs to divide patients into groups and estimated the effects of the RMA
      on each. RESULTS: Objective 1. LOS fell from 297.8 min pre-RMA to 261.7 min
      during RMA, an improvement of 36.1 (95% confidence interval 21.8-50.4) min; LWBS
      did not change significantly. Objective 2. Patients seen and dispositioned by the
      RMA had an estimated decrease in LOS of 117.8 min (estimated decrease in LOS of
      45%), but patients seen by the RMA whose care was transitioned to the main ED had
      an estimated increase in LOS of 25.0 min (estimated increase in LOS of 8%).
      CONCLUSIONS: On a system level, the addition of an RMA shift at a single facility
      was associated with an improvement in LOS, but not LWBS. On a mechanistic level,
      it seems that improvements occurred as a result of the rapid disposition
      component of the RMA rather than placing advanced orders at triage.

PMID- 25769940
TI  - Extrinsic origins of the somatostatin and neuropeptide Y innervation of the rat
      basolateral amygdala.
AB  - The amygdalar basolateral nuclear complex (BLC) is a cortex-like structure that
      receives inputs from many cortical areas. It has long been assumed that cortico
      amygdalar projections, as well as inter-areal intracortical connections, arise
      from cortical pyramidal cells. However, recent studies have shown that GABAergic
      long-range nonpyramidal neurons (LRNP neurons) in the cortex also contribute to
      inter-areal connections. The present study combined Fluorogold (FG) retrograde
      tract tracing with immunohistochemistry for cortical nonpyramidal neuronal
      markers to determine if cortical LRNP neurons project to the BLC in the rat.
      Injections of FG into the BLC produced widespread retrograde labeling in the
      cerebral hemispheres and diencephalon. Triple-labeling for FG, somatostatin
      (SOM), and neuropeptide Y (NPY) revealed a small number of FG+/SOM+/NPY+ neurons
      and FG+/SOM+/NPY- neurons in the lateral entorhinal area, amygdalopiriform
      transition area, and piriform cortex, but not in the prefrontal and insular
      cortices, or in the diencephalon. In addition, FG+/SOM+/NPY+ neurons were
      observed in the amygdalostriatal transition area and in a zone surrounding the
      intercalated nuclei. About half of the SOM+ neurons in the lateral entorhinal
      area labeled by FG were GABA+. FG+ neurons containing parvalbumin were only seen
      in the basal forebrain, and no FG+ neurons containing vasoactive intestinal
      peptide were observed in any brain region. Since LRNP neurons involved in
      corticocortical connections are critical for synchronous oscillations that allow
      temporal coordination between distant cortical regions, the LRNP neurons
      identified in this study may play a role in the synchronous oscillations of the
      BLC and hippocampal region that are involved in the retrieval of fear memories.

PMID- 25769941
TI  - Effects of chronic doxepin and amitriptyline administration in naive mice and in
      neuropathic pain mice model.
AB  - Neuropathic pain is a severe clinical problem, often appearing as a co-symptom of
      many diseases or manifesting as a result of damage to the nervous system. Many
      drugs and agents are currently used for the treatment of neuropathic pain, such
      as tricyclic antidepressants (TCAs). The aims of this paper were to test the
      effects of two classic TCAs, doxepin and amitriptyline, in naive animals and in a
      model of neuropathic pain and to determine the role of cytokine activation in the
      effects of these drugs. All experiments were carried out with Albino-Swiss mice
      using behavioral tests (von Frey test and the cold plate test) and biochemical
      analyses (qRT-PCR and Western blot). In the mice subjected to chronic
      constriction injury (CCI), doxepin and amitriptyline attenuated the symptoms of
      neuropathic pain and diminished the CCI-induced increase in the levels of spinal
      interleukin (IL)-6 and -1beta mRNA, but not the protein levels of these
      cytokines, measured on day 12. Unexpectedly, chronic administration of doxepin or
      amitriptyline for 12 days produced allodynia and hyperalgesia in naive mice. The
      treatment with these drugs did not influence the spinal levels of IL-1beta and IL
      6 mRNA, however, the protein levels of these pronociceptive factors were
      increased. The administration of ondansetron (5-HT3 receptor antagonist)
      significantly weakened the allodynia and hyperalgesia induced by both
      antidepressants in naive mice; in contrast, yohimbine (alpha2-adrenergic
      receptors antagonist) did not influence these effects. Allodynia and hyperalgesia
      induced in naive animals by amitriptyline and doxepin may be associated with an
      increase in the levels of pronociceptive cytokines resulting from 5-HT3-induced
      hypersensitivity. Our results provide new and important information about the
      possible side effects of antidepressants. Further investigation of these
      mechanisms may help to guide decisions about the use of classic TCAs for therapy.

PMID- 25769942
TI  - Why preferring parametric forecasting to nonparametric methods?
AB  - A recent series of papers by Charles T. Perretti and collaborators have shown
      that nonparametric forecasting methods can outperform parametric methods in noisy
      nonlinear systems. Such a situation can arise because of two main reasons: the
      instability of parametric inference procedures in chaotic systems which can lead
      to biased parameter estimates, and the discrepancy between the real system
      dynamics and the modeled one, a problem that Perretti and collaborators call "the
      true model myth". Should ecologists go on using the demanding parametric
      machinery when trying to forecast the dynamics of complex ecosystems? Or should
      they rely on the elegant nonparametric approach that appears so promising? It
      will be here argued that ecological forecasting based on parametric models
      presents two key comparative advantages over nonparametric approaches. First, the
      likelihood of parametric forecasting failure can be diagnosed thanks to simple
      Bayesian model checking procedures. Second, when parametric forecasting is
      diagnosed to be reliable, forecasting uncertainty can be estimated on virtual
      data generated with the fitted to data parametric model. In contrast,
      nonparametric techniques provide forecasts with unknown reliability. This
      argumentation is illustrated with the simple theta-logistic model that was
      previously used by Perretti and collaborators to make their point. It should
      convince ecologists to stick to standard parametric approaches, until methods
      have been developed to assess the reliability of nonparametric forecasting. 

PMID- 25769943
TI  - Modeling shortest path selection of the ant Linepithema humile using
      psychophysical theory and realistic parameter values.
AB  - The emergence of self-organizing behavior in ants has been modeled in various
      theoretical approaches in the past decades. One model explains experimental
      observations in which Argentine ants (Linepithema humile) selected the shorter of
      two alternative paths from their nest to a food source (shortest path
      experiments). This model serves as an important example for the emergence of
      collective behavior and self-organization in biological systems. In addition, it
      inspired the development of computer algorithms for optimization problems called
      ant colony optimization (ACO). In the model, a choice function describing how
      ants react to different pheromone concentrations is fundamental. However, the
      parameters of the choice function were not deduced experimentally but freely
      adapted so that the model fitted the observations of the shortest path
      experiments. Thus, important knowledge was lacking about crucial model
      assumptions. A recent study on the Argentine ant provided this information by
      measuring the response of the ants to varying pheromone concentrations. In said
      study, the above mentioned choice function was fitted to the experimental data
      and its parameters were deduced. In addition, a psychometric function was fitted
      to the data and its parameters deduced. Based on these findings, it is possible
      to test the shortest path model by applying realistic parameter values. Here we
      present the results of such tests using Monte Carlo simulations of shortest path
      experiments with Argentine ants. We compare the choice function and the
      psychometric function, both with parameter values deduced from the above
      mentioned experiments. Our results show that by applying the psychometric
      function, the shortest path experiments can be explained satisfactorily by the
      model. The study represents the first example of how psychophysical theory can be
      used to understand and model collective foraging behavior of ants based on trail
      pheromones. These findings may be important for other models of pheromone guided
      ant behavior and might inspire improved ACO algorithms. 

PMID- 25769944
TI  - On estimating the reliability of ecological forecasts.
AB  - Recent work has highlighted the utility of nonparametric forecasting methods for
      predicting ecological time series (Perretti et al., 2013. Proc. Natl. Acad. Sci.
      U.S.A. 110, 5253-5257). However, one topic that has received considerably less
      attention is the quantification of uncertainty in nonparametric forecasts. This
      important topic was brought to the forefront in the recent work by Jabot (2014.
      J. Theor. Biol.). Here, we add to this emerging discussion by reviewing the
      available methods for quantifying forecast uncertainty in nonparametric models.
      We conclude with a demonstration of one such method using the simulation model of
      Jabot (2014. J. Theor. Biol.). We find that nonparametric forecast error is
      accurately estimated with as few as 10 observations in the time series. 

PMID- 25769945
TI  - Suction power output and the inertial cost of rotating the neurocranium to
      generate suction in fish.
AB  - To expand the buccal cavity, many suction-feeding fishes rely on a considerable
      contribution from dorsal rotation of the dorsal part of the head including the
      brains, eyes, and several bones forming the braincase and skull roof (jointly
      referred to as the neurocranium). As the neurocranium takes up a large part of
      the total mass of the head, this rotation may incur a considerable inertial cost.
      If so, this would suggest a significant selective pressure on the kinematics and
      mass distribution of the neurocranium of suction feeders. Here, an inverse
      dynamic model is formulated to calculate the instantaneous power required to
      rotate the neurocranium, approximated by a quarter ellipsoid volume of
      homogeneous density, as well as to calculate the instantaneous suction power
      based on intra-oral pressure and head volume quantifications. We applied this
      model to largemouth bass (Micropterus salmoides) and found that the power
      required to rotate the neurocranium accounts for only about 4% of the power
      required to suck water into the mouth. Furthermore, recovery of kinetic energy
      from the rotating neurocranium converted into suction work may be possible during
      the phase of neurocranial deceleration. Thus, we suggest that only a negligible
      proportion of the power output of the feeding muscles is lost as inertial costs
      in the largemouth bass. Consequently, the feeding performance of piscivorous
      suction feeders with generalised morphology, comparable to our model species, is
      not limited by neurocranial motion during head expansion. This suggests that it
      is thus not likely to be a factor of importance in the evolution of cranial shape
      and size. 

PMID- 25769946
TI  - The role of infections in Behcet disease and neuro-Behcet syndrome.
AB  - Infections are considered an environmental trigger for exacerbations of immune
      mediated diseases. We aimed to establish if common viral infections could be
      identified as a precipitant of Behcet disease (BD) with or without neurological
      involvement and to assess the variability of the immune response to common
      viruses. We also investigated whether cytokines and chemokines could be markers
      of neurological involvement. Finally, we explored if anti-basal ganglia
      antibodies (ABGAs) would be associated with neurological involvement in BD. Our
      study included 14 individuals with BD with neurological involvement (neuroBehcet
      syndrome - NBS), 16 individuals with BD without neurological involvement and 18
      healthy controls (HC). Overall we found a tendency for increased levels of anti
      viral IgG antibody levels in BD, more evident in NBS patients versus HC. Epstein
      Barr viral-capsid antigen IgG titres were increased in NBS patients versus other
      BD patients (p=0.032). Anti-measles antibody titres induced by vaccination were
      similarly elevated. ABGAs were not detected in the serum of our cohort. Raised
      levels of serum IL-8 in some BD patients did not reflect clinical activity or
      severity. In conclusion, there was evidence for a polyclonal immune activation
      rather than a specific virus effect in the sera of individuals with BD or NBS. 

PMID- 25769947
TI  - Influenza A virus PB1-F2 is involved in regulation of cellular redox state in
      alveolar epithelial cells.
AB  - Occurrence of oxidative stress is common in influenza, and renders the host more
      susceptible to pathogenic effects including cell death. We previously reported
      that down-regulation of superoxide anion dismutase 1 (SOD1) by influenza A virus
      (IAV) resulted in a significant increase in the levels of reactive oxygen species
      (ROS) and viral PB1 polymerase gene product in the early stage of infection.
      However, the precise molecular mechanism of IAV-mediated ROS generation is not
      yet fully understood. In this study, we investigated the possible involvement of
      the key virulence factor PB1-F2 in ROS generation and its contribution to the
      viral propagation and cell death. The key virulence factor PB1-F2 was found to be
      responsible, at least in part, for the ROS generation through lowering the SOD1
      level in alveolar epithelial A549 cells. PB1-F2 overexpression resulted in SOD1
      diminishment and ROS enhancement, while another virulent factor, NS1, did not
      show significant changes. Inversely, we examined the effects of the absence of
      PB1-F2 using mutant IAV lacking PB1-F2 expression (mutantDeltaF2). Infection with
      mutantDeltaF2 virus did not significantly lower the SOD1 level, and thus
      generated moderately low levels of ROS. In addition, the oxidative activity of
      PB1-F2 was directly reflected by cell viability and death. Infection with the
      mutant virus reduced the percentage of apoptotic cells more than two-fold
      compared to the wild-type IAV in A549 cells. Furthermore, expression of exogenous
      SOD1 gene abrogated a large portion of the PB1-F2-induced apoptosis of cells
      infected with wild-type IAV, but affected much less of the mutantDeltaF2 virus
      infected cells. These results suggest that the PB1-F2 is directly implicated in
      virus-induced oxidative stress, thereby contributing to the early stages of IAV
      replication cycle and ultimately to disease severity. 

PMID- 25769948
TI  - Parasitism and survival rate of Diadegma fenestrale (Hymenoptera: Ichneumonidae)
      and DfIV gene expression patterns in two lepidopteran hosts.
AB  - The genus Diadegma is a well-known parasitoid group and some are known to have
      symbiotic virus, polydnavirus (PDV). A novel IV was discovered from the calyx of
      Diadegma fenestrale female and sequenced its genome. D. fenestrale has more than
      two hosts, including potato tuber moth (PTM) and diamondback moth (DBM). D.
      fenestrale preferred PTM to DBM as hosts based on the oviposition and survival
      rate. Nevertheless, the developmental period and morphology of D. fenestrale were
      not significantly different between PTM and DBM. We compared DfIV gene expression
      patterns between PTM and DBM under various conditions to understand the
      phenomena. DfIV genes were more widely expressed in PTM with large numbers than
      in DBM after parasitized by D. fenestrale, particularly at the initial point.
      They showed differential expression patterns between two lepidopteran hosts. This
      DfIV gene expression plasticity showed a dependency on the lepidopteran host
      species and parasitization time, suggesting that it may contribute to increase
      the parasitoid survival rate. This might be one of the key elements that
      determine the symbiotic relationship between PDV and parasitoid. 

PMID- 25769949
TI  - miR-21 modulates resistance of HR-HPV positive cervical cancer cells to radiation
      through targeting LATS1.
AB  - Although multiple miRNAs are found involved in radioresistance development in HR
      HPV positive (+) cervical cancer, only limited studies explored the regulative
      mechanism of the miRNAs. miR-21 is one of the miRNAs significantly upregulated in
      HR-HPV (+) cervical cancer is also significantly associated with radioresistance.
      However, the detailed regulative network of miR-21 in radioresistance is still
      not clear. In this study, we confirmed that miR-21 overexpression was associated
      with higher level of radioresistance in HR-HPV (+) cervical cancer patients and
      thus decided to further explore its role. Findings of this study found miR-21 can
      negatively affect radiosensitivity of HR-HPV (+) cervical cancer cells and
      decrease radiation induced G2/M block and increase S phase accumulation. By using
      dual luciferase assay, we verified a binding site between miR-21 and 3'-UTR of
      large tumor suppressor kinase 1 (LATS1). Through direct binding, miR-21 can
      regulate LATS1 expression in cervical cancer cells. LATS1 overexpression can
      reverse miR-21 induced higher colony formation rate and also reduced miR-21
      induced S phase accumulation and G2/M phase block reduction under radiation
      treatment. These results suggested that miR-21-LATS1 axis plays an important role
      in regulating radiosensitivity. 

PMID- 25769950
TI  - PEGylated lysozymes with anti-septic effects in human endothelial cells and in
      mice.
AB  - High mobility group box 1 (HMGB1) was recently shown to be an important
      extracellular mediator of severe vascular inflammatory disease, sepsis. Lysozyme
      (LYZ) has been shown to bind to bacterial lipopolysaccharide (LPS) and have a
      potential for playing a role in the therapy of inflammatory diseases. However,
      the effect of LYZ on HMGB1-induced septic response has not been investigated.
      Moreover, PEGylation effects on the antiseptic activity of LYZ are not known.
      Here, we show, for the first time, the anti-septic effects of PEGylated LYZ (PEG
      LYZ) in HMGB1-mediated inflammatory responses in vitro and in vivo. Among four
      mono-PEGylated LYZs with different PEGylation sites (N-terminus, Lys(13),
      Lys(33), and Lys(97)), N-terminally PEGylated LYZ showed the highest activity.
      Subsequently, among three N-terminally PEGylated LYZs prepared with aldehyde
      activated PEGs of 5, 10, and 20 kDa, 5 kDa-PEG-conjugated LYZ (P5-K(1)-LYZ)
      showed the highest antiseptic activity. The data showed that P5-K(1)-LYZ post
      treatment effectively suppressed LPS-mediated release of HMGB1. P5-K(1)-LYZ also
      inhibited HMGB1-mediated hyperpermeability in human endothelial cells.
      Furthermore, P5-K(1)-LYZ reduced the cecal ligation and puncture (CLP)-induced
      release of HMGB1 and septic mortality. Collectively, these results suggest P5
      K(1)-LYZ as a candidate therapeutic agent for the treatment of vascular
      inflammatory diseases via inhibition of the HMGB1 signaling pathway. 

PMID- 25769951
TI  - Solution structure and functional studies of the highly potent equine
      antimicrobial peptide DEFA1.
AB  - Defensins are small effector molecules of the innate immune system that are
      present in almost all organisms including plants and animals. These peptides
      possess antimicrobial activity against a broad range of microbes including
      bacteria, fungi and viruses and act as endogenous antibiotics. alpha-Defensins
      are a subfamily of the defensin family and their expression is limited to
      specific tissues. Equine DEFA1 is an enteric alpha-defensin exclusively secreted
      by Paneth cells and shows an activity against a broad spectrum of microbes,
      including typical pathogens of the horse such as Rhodococcus equi, various
      streptococci strains, Salmonella choleraesuis, and Pasteurella multocida. Here,
      we report the three-dimensional structure of DEFA1 solved by NMR-spectroscopy and
      demonstrate its specific function of aggregating various phospholipids. 

PMID- 25769952
TI  - Phosphoinositide-dependent kinase 1 regulates leukemia stem cell maintenance in
      MLL-AF9-induced murine acute myeloid leukemia.
AB  - Although great efforts have been made to improve available therapies, the
      mortality rate of acute myeloid leukemia (AML) remains high due to poor treatment
      response and frequent relapse after chemotherapy. Leukemia stem cells (LSCs) are
      thought to account for this poor prognosis and relapse. Phosphoinositide
      dependent kinase 1 (PDK1) is a critical regulator of the PI3K/Akt pathway and has
      been shown to be frequently activated in leukemia. However, the role of PDK1 in
      the regulation of LSCs in AML is still not clear. Using a PDK1 conditional
      deletion MLL-AF9 murine AML model, we revealed that the deletion of PDK1
      prolonged the survival of AML mice by inducing LSC apoptosis. This was
      accompanied by the increased expression of the pro-apoptotic genes Bax and p53
      and the reduced expression of Stat5, which has been shown to be constitutively
      activated in leukemia. Thus, our findings suggest that PDK1 plays an essential
      role in maintaining LSCs. Further delineating the function of PDK1 in LSCs may
      provide a new strategy for the improved treatment of AML relapse. 

PMID- 25769953
TI  - Phosphorylation of myosin II regulatory light chain by ZIP kinase is responsible
      for cleavage furrow ingression during cell division in mammalian cultured cells.
AB  - Zipper-interacting protein kinase (ZIPK) is known to regulate several functions
      such as apoptosis, smooth muscle contraction, and cell migration. While
      exogenously expressed GFP-ZIPK localizes to the cleavage furrow, role of ZIPK in
      cytokinesis is obscure. Here, we show that ZIPK is a major MRLC kinase during
      mitosis. Moreover, ZIPK siRNA-mediated knockdown causes delay of cytokinesis. The
      delay in cytokinesis of ZIPK-knockdown cells was rescued by the exogenous
      diphosphorylation-mimicking MRLC mutant. Taken together, these findings suggest
      that ZIPK plays a role in the progression and completion of cytokinesis through
      MRLC phosphorylation. 

PMID- 25769954
TI  - NMR ((1)H and (13)C) based signatures of abnormal choline metabolism in oral
      squamous cell carcinoma with no prominent Warburg effect.
AB  - At functional levels, besides genes and proteins, changes in metabolome profiles
      are instructive for a biological system in health and disease including
      malignancy. It is understood that metabolomic alterations in association with
      proteomic and transcriptomic aberrations are very fundamental to unravel
      malignant micro-ambient criticality and oral cancer is no exception. Hence
      deciphering intricate dimensions of oral cancer metabolism may be contributory
      both for integrated appreciation of its pathogenesis and to identify any critical
      but yet unexplored dimension of this malignancy with high mortality rate.
      Although several methods do exist, NMR provides higher analytical precision in
      identification of cancer metabolomic signature. Present study explored abnormal
      signatures in choline metabolism in oral squamous cell carcinoma (OSCC) using
      (1)H and (13)C NMR analysis of serum. It has demonstrated down-regulation of
      choline with concomitant up-regulation of its break-down product in the form of
      trimethylamine N-oxide in OSCC compared to normal counterpart. Further, no
      significant change in lactate profile in OSCC possibly indicated that well-known
      Warburg effect was not a prominent phenomenon in such malignancy. Amongst other
      important metabolites, malonate has shown up-regulation but d-glucose, saturated
      fatty acids, acetate and threonine did not show any significant change. Analyzing
      these metabolomic findings present study proposed trimethyl amine N-oxide and
      malonate as important metabolic signature for oral cancer with no prominent
      Warburg effect. 

PMID- 25769955
TI  - Design, expression, and characterization of a novel dendritic cell-targeted
      proteins.
AB  - In vivo approaches to inducing an effective immune response focus on targeted
      antigen (Ag) delivery to dendritic cells (DCs). In this study, we developed a new
      method of targeting plasmid DNA and/or the antigen (Ag)-antibody (Ab) complex to
      DCs via the DC receptor DEC-205, also known as cluster of differentiation CD205.
      We cloned and expressed a recombinant protein composed of mouse DEC-205-specific
      single-chain fragment variable region (mDEC-205-scFv), the streptococcal protein
      G (SPG) IgG-binding domain and cationic peptide (CP), which named mDEC205-scFv
      SPG-CP (msSC). In vitro, the recombinant protein msSC can specifically bind to
      DCs through the section of mDEC-205-scFv, and bound the Ag-Ab complex via SPG as
      well as plasmid DNA through electrostatic bonding with CP in vitro. In addition,
      msSC functioned in a manner similar to anti-DEC-205 monoclonal Ab and bound to
      mouse bone marrow-derived DCs. It was demonstrated in vivo that msSC can target
      plasmid DNA to DCs, resulting in efficient uptake and expression. Moreover, msSC
      can form a complex with pGL3-CMV and transport it to draining lymph nodes when
      injected in vivo. These results indicate that msSC can be used as a carrier
      protein for vaccine delivery to DCs via formation of plasmid DNA-Ag-Ab ternary
      complexes. 

PMID- 25769956
TI  - Zerumbone protects INS-1 rat pancreatic beta cells from high glucose-induced
      apoptosis through generation of reactive oxygen species.
AB  - The aim of this study is to explore the effect of zerumbone, a natural
      sesquiterpene isolated from Zingiber zerumbet Smith, on high glucose-induced
      cytotoxicity in pancreatic beta cells. INS-1 rat pancreatic beta cells were
      treated with 33 mM glucose with or without different concentrations of zerumbone
      and cell viability and apoptosis were assessed. The involvement of reactive
      oxygen species (ROS) and mitogen-activated protein kinase (MAPK) signaling in the
      action of zerumbone was examined. Notably, zerumbone significantly (P < 0.05)
      prevented the reduction of cell viability induced by high glucose. Such
      protection was in a concentration-dependent fashion up to 60 MUM of zerumbone.
      Annexin-V/propidium iodide staining analysis showed that zerumbone impaired the
      apoptotic response of high glucose-treated INS-1 cells, which was coupled with a
      significant decline in cleaved caspase-3 and caspase-9. Pretreatment with the ROS
      inhibitor N-acetylcysteine abrogated the phosphorylation of p38 and JNK induced
      by high glucose. Zerumbone significantly (P < 0.05) decreased the generation of
      ROS and the phosphorylation of p38 and JNK MAPKs in high glucose-treated INS-1
      cells. Pharmacological activation of p38 and JNK with anisomycin reversed the
      anti-apoptotic effect of zerumbone. Additionally, simultaneous inhibition of p38
      and JNK significantly (P < 0.05) reduced the apoptotic response in high glucose
      treated INS-1 cells. In conclusion, zerumbone confers protection against high
      glucose-induced apoptosis of INS-1 pancreatic beta cells, largely through
      interfering with ROS production and p38 and JNK activation. Zerumbone may have
      potential therapeutic effects against hyperglycemia-induced beta cell damage in
      diabetes.

PMID- 25769957
TI  - Single chain antibody fragment with serine protease inhibitory property capable
      of neutralizing toxicity of Trimeresurus mucrosquamatus venom.
AB  - Trimeresurus mucrosquamatus (TM) is one of majorities of snake envenomation with
      necrotic and hemorrhagic toxin in Taiwan. In this study, chickens were used as an
      alternative animal model for immunization with TM venom. Using phage display
      technology to process four rounds of panning, selected single chain variable
      fragments (scFv) could specifically recognize TM venom proteins, which were later
      identified as a group of homogeneous venom serine protease. The specific scFv
      antibodies showed various inhibitory effects on sheep RBC lysis induced by TM
      venom using an indirect hemolytic assay in vitro. In addition, the survival times
      of mice were extended to certain degrees when treated with these scFv antibodies
      individually or in a combination. To elucidate the inhibitory mechanism, we used
      molecular modeling to build up the serine protease structure to simulate the
      possible interactions with scFv antibodies. The results suggested that the CDR
      loop of the scFv antibodies (3S10 or 4S1) might bind at the 99-loop of venom
      serine protease so as to affect substrate access due to the partial collapse of
      the subsite S2 and the partial movement of the subsite S4. It is hoped these
      chicken-derived antibodies could be applied to develop diagnostic and therapeutic
      agents against snakebites.

PMID- 25769958
TI  - Extracellular acidification synergizes with PDGF to stimulate migration of mouse
      embryo fibroblasts through activation of p38MAPK with a PTX-sensitive manner.
AB  - The elucidation of the functional mechanisms of extracellular acidification
      stimulating intracellular signaling pathway is of great importance for developing
      new targets of treatment for solid tumors, and inflammatory disorders
      characterized by extracellular acidification. In the present study, we focus on
      the regulation of extracellular acidification on intracellular signaling pathways
      in mouse embryo fibroblasts (MEFs). We found extracellular acidification was at
      least partly involved in stimulating p38MAPK pathway through PTX-sensitive
      behavior to enhance cell migration in the presence or absence of platelet-derived
      growth factor (PDGF). Statistical analysis showed that the actions of
      extracellular acidic pH and PDGF on inducing enhancement of cell migration were
      not an additive effect. However, we also found extracellular acidic pH did
      inhibit the viability and proliferation of MEFs, suggesting that extracellular
      acidification stimulates cell migration probably through proton-sensing
      mechanisms within MEFs. Using OGR1-, GPR4-, and TDAG8-gene knock out technology,
      and real-time qPCR, we found known proton-sensing G protein-coupled receptors
      (GPCRs), transient receptor potential vanilloid subtype 1 (TRPV1), and acid
      sensing ion channels (ASICs) were unlikely to be involved in the regulation of
      acidification on cell migration. In conclusion, our present study validates that
      extracellular acidification stimulates chemotactic migration of MEFs through
      activation of p38MAPK with a PTX-sensitive mechanism either by itself, or
      synergistically with PDGF, which was not regulated by the known proton-sensing
      GPCRs, TRPV1, or ASICs. Our results suggested that others proton-sensing GPCRs or
      ion channels might exist in MEFs, which mediates cell migration induced by
      extracellular acidification in the presence or absence of PDGF. 

PMID- 25769959
TI  - Postprandial hypotension is associated with more rapid gastric emptying in
      healthy older individuals.
AB  - BACKGROUND: Postprandial hypotension (PPH) occurs frequently in older individuals
      with disease and/or living in residential care, but its prevalence in "healthy"
      older individuals has not been evaluated in large cohorts. PPH is associated with
      substantial morbidity and increased mortality; current management is suboptimal.
      Recent studies suggest that the magnitude of the postprandial fall in blood
      pressure (BP) is related to the rate of gastric emptying (GE), so that relatively
      more rapid GE may potentially be a risk factor for PPH. We aimed to determine the
      prevalence of, and evaluate the association of GE with PPH. METHODS: A total of
      88 healthy "older", community-dwelling residents (47 women, 41 men; age 71.0 +/-
      0.5 years) attended a clinical research laboratory on a single occasion.
      Individuals consumed a 300 mL drink containing 75 g glucose and 150 mg C(13)
      acetate. Exhaled breath was obtained for analysis of (13)CO2 and calculation of
      the 50% GE time (T50). BP and heart rate were assessed with an automated device.
      RESULTS: Eleven (12.8%) of 86 subjects had PPH (2 had diabetes and were
      excluded). GE was faster in subjects with PPH than the remainder of the group
      (T50 118.0 +/- 9.4 vs 142.3 +/- 4.6 minutes, P < .05). CONCLUSIONS: We conclude
      the prevalence of PPH in a cohort of otherwise healthy "older" individuals is
      12.8% and PPH is associated with relatively more rapid GE. Therapies that slow GE
      may be useful in the management of PPH.

PMID- 25769960
TI  - Impact of tai-chi on falls among preclinically disabled older people. A
      randomized controlled trial.
AB  - OBJECTIVE: To investigate the effectiveness of tai-chi in preventing falls among
      community-dwelling older people. DESIGN: Multisite parallel group individually
      randomized controlled trial. SETTING: Melbourne, Australia. PARTICIPANTS:
      Preclinically disabled community-dwelling people 70 + years (n = 503), without
      major medical conditions or moderate to severe cognitive impairment.
      INTERVENTION: Sixty-minute modified Sun style tai-chi group-based exercise
      program twice weekly for 48 weeks; control intervention was a seated group-based
      flexibility exercise program of the same dose. MEASUREMENTS: All falls, self
      reported using a monthly calendar, analyzed at 24 weeks and 48 weeks. Injurious
      falls reported in follow-up telephone interviews for each reported fall. RESULTS:
      The adjusted fall incidence rate ratios at 24 and 48 weeks were 1.08 [(95%
      confidence interval (CI) 0.64-1.81)], and 1.12 (95% CI 0.75-1.67), respectively.
      A higher proportion of intervention participants ceased attendance in the first
      24 weeks (difference 17.9%, 95% CI 9.6-25.8), and the second 24 weeks (2.7%, 95%
      CI -5.0 to 10.4). Intervention participants who ceased attendance had lower left
      quadriceps strength (difference 3.3 kg 95% CI 0.15-6.36) and required longer to
      complete the timed up and go test (difference 1.7 seconds 95% CI 0.22-3.17) at
      baseline. CONCLUSIONS: This study does not support modified Sun style tai-chi as
      a falls prevention measure among relatively well community-dwelling older people
      with modified mobility and at increased risk of disability. Insufficient
      intervention intensity, or low exercise class attendance may have contributed to
      the lack of effect, as may have attrition bias among the intervention group.

PMID- 25769961
TI  - Organizational Factors Associated With Inappropriate Neuroleptic Drug Prescribing
      in Nursing Homes: A Multilevel Approach.
AB  - OBJECTIVE: To determine whether the number of attending general practitioners
      (GPs) in nursing homes and other facility characteristics are associated with
      inappropriate neuroleptic prescribing. DESIGN: Cross-sectional study. SETTING:
      One hundred seventy-five nursing homes in France participating in the IQUARE
      (Impact d'une demarche QUAlite sur l'evolution des pratiques et le declin
      fonctionnel des Residents en EHPAD) study. PARTICIPANTS: A total of 6275
      residents included between May and July 2011. MEASUREMENTS: The outcome measure
      was potentially inappropriate prescribing of neuroleptic drugs according to the
      approved indications and French guidelines. Resident characteristics and nursing
      home characteristics were electronically recorded by the nursing home's
      coordinating physician. Because of the hierarchical structure of data (resident
      level and nursing home level), multivariate analysis using a multilevel binary
      logistic model was carried out to investigate factors associated with
      inappropriate neuroleptic prescribing. RESULTS: Of 6275 residents enrolled, 1532
      (24.4%) had at least 1 prescription for a neuroleptic drug. This corresponded to
      513 residents (33.5%) with appropriate prescribing (with regard to indication,
      substance and dose) and 1019 (66.5%) with potentially inappropriate prescribing.
      The multilevel binary logistic model showed that residents who lived in a nursing
      home with 30 GPs or more/100 beds had a higher likelihood of potentially
      inappropriate prescription than those who lived in nursing homes with fewer than
      10 GPs/100 beds [adjusted odds ratio (aOR) 1.80; 95% confidence interval (CI)
      1.04-3.12]. Residents who were >= 85 years old and those with dementia were more
      likely to have inappropriate prescription (aOR 1.75; 95% CI 1.32-2.32 and aOR,
      2.06; 95% CI 1.56-2.74, respectively) such as the statement "no psychotropic drug
      prescription," whereas the resident did in fact have a prescription (aOR 1.96;
      95% CI 1.03-3.74). CONCLUSIONS: Organizational difficulties because of a large
      number of physicians probably explain the association with inappropriate
      prescribing of neuroleptics.

PMID- 25769962
TI  - Frailty Index and Mortality in Nursing Home Residents in France: Results From the
      INCUR Study.
AB  - OBJECTIVE: The objective of this study was to examine whether the capacity of an
      age-related deficit accumulation index (the so-called Frailty Index [FI] proposed
      by Rockwood) to predict mortality in a nursing home population. DESIGN, SETTING,
      AND PARTICIPANTS: Data are from a longitudinal cohort study (ie, the Incidence of
      pNeumonia and related ConseqUences in nursing home Residents [INCUR]) of 773
      older persons (74.4% women) living in 13 French nursing homes. MEASUREMENTS: The
      FI was computed as the ratio between actual and 30 potential deficits the
      participant might have presented at the baseline visit (range between 0 [no
      deficit] and 1 [30 deficits]). Death events were monitored and detected over a 12
      month follow-up. The risk of death was estimated using Cox proportional hazards
      models. RESULTS: Mean age of participants was 86.2 (SD 7.5) years, with a mean FI
      of 0.35 (SD 0.11). At the end of the follow-up, 135 (17.4%) death events were
      recorded. A positive association between the FI and mortality (per 0.01 FI
      increment: age- and gender-adjusted hazard ratio 1.018, 95% confidence interval
      1.002-1.035, P = .03) was reported. The use of the traditional 0.25 cut-point for
      detecting the frailty status is inadequate in this population. CONCLUSION: The FI
      is able to predict mortality even in very old and complex elders, such as nursing
      home residents.

PMID- 25769963
TI  - Cancer surgery: how may anesthesia influence outcome?
AB  - OBJECTIVE: To review the published literature regarding the effects of anesthesia
      on cancer surgery to prevent tumor cell proliferation/migration or induce
      apoptosis. BACKGROUND: Surgery is the main treatment for potentially curable
      solid tumors, but most cancer-related deaths in patients who have received
      previous surgical treatment are caused by metastatic disease. There is increasing
      evidence that anesthetic technique has the potential to affect long-term outcome
      after cancer surgery. METHODS: This work reviews the English published literature
      that was obtained by performing a search of the PubMed database up to January
      2014. We selected articles that provided evidence or reviewed the possible
      actions of anesthetics on cancer cells or the influence of anesthesia in
      recurrence/outcome. RESULTS: Inhaled anesthetics induce immunosuppression and
      activate inflammatory cascade activation, whereas propofol has a protective
      action. Opioids might promote cancer recurrence and metastasis. In vitro and in
      vivo studies have demonstrated that local anesthetics inhibit proliferation and
      migration of cancer cells and induce apoptosis. CONCLUSIONS: Anesthesiologists
      should follow current best clinical practice and include all strategies that
      effectively decrease pain and attenuate stress. Regional anesthesia and
      multimodal analgesia, adding anti-inflammatory drugs, play an unquestionable role
      in the control of perioperative pain and may improve recurrence-free survival.

PMID- 25769965
TI  - The great escape; the hallmarks of resistance to antiangiogenic therapy.
AB  - The concept of antiangiogenic therapy in cancer treatment has led to the approval
      of different agents, most of them targeting the well known vascular endothelial
      growth factor pathway. Despite promising results in preclinical studies, the
      efficacy of antiangiogenic therapy in the clinical setting remains limited.
      Recently, awareness has emerged on resistance to antiangiogenic therapies. It has
      become apparent that the intricate complex interplay between tumors and stromal
      cells, including endothelial cells and associated mural cells, allows for escape
      mechanisms to arise that counteract the effects of these targeted therapeutics.
      Here, we review and discuss known and novel mechanisms that contribute to
      resistance against antiangiogenic therapy and provide an outlook to possible
      improvements in therapeutic approaches. 

PMID- 25769964
TI  - Modification of sphingolipid metabolism by tamoxifen and N-desmethyltamoxifen in
      acute myelogenous leukemia--Impact on enzyme activity and response to cytotoxics.
AB  - The triphenylethylene antiestrogen, tamoxifen, can be an effective inhibitor of
      sphingolipid metabolism. This off-target activity makes tamoxifen an interesting
      ancillary for boosting the apoptosis-inducing properties of ceramide, a
      sphingolipid with valuable tumor censoring activity. Here we show for the first
      time that tamoxifen and metabolite, N-desmethyltamoxifen (DMT), block ceramide
      glycosylation and inhibit ceramide hydrolysis (by acid ceramidase, AC) in human
      acute myelogenous leukemia (AML) cell lines and in AML cells derived from
      patients. Tamoxifen (1-10 MUM) inhibition of AC in AML cells was accompanied by
      decreases in AC protein expression. Tamoxifen also depressed expression and
      activity of sphingosine kinase 1 (SphK1), the enzyme-catalyzing production of
      mitogenic sphingosine 1-phosphate (S1-P). Results from mass spectroscopy showed
      that tamoxifen and DMT (i) increased the levels of endogenous C16:0 and C24:1
      ceramide molecular species, (ii) nearly totally halted production of respective
      glucosylceramide (GC) molecular species, (iii) drastically reduced levels of
      sphingosine (to 9% of control), and (iv) reduced levels of S1-P by 85%, in
      vincristine-resistant HL-60/VCR cells. The co-administration of tamoxifen with
      either N-(4-hydroxyphenyl)retinamide (4-HPR), a ceramide-generating retinoid, or
      a cell-deliverable form of ceramide, C6-ceramide, resulted in marked decreases in
      HL-60/VCR cell viability that far exceeded single agent potency. Combination
      treatments resulted in synergistic apoptotic cell death as gauged by increased
      Annexin V binding and DNA fragmentation and activation of caspase-3. These
      results show the versatility of adjuvant triphenylethylene with ceramide-centric
      therapies for magnifying therapeutic potential in AML. Such drug regimens could
      serve as effective strategies, even in the multidrug-resistant setting.

PMID- 25769966
TI  - Editorial: medicinal chemistry studies of neglected diseases.

PMID- 25769967
TI  - High-throughput drug repositioning for the discovery of new treatments for Chagas
      disease.
AB  - Despite affecting around 8 million people worldwide and representing an economic
      burden above &#36;7 billion/ year, currently approved medications to treat Chagas
      disease are still limited to two drugs, nifurtimox and benznidazole, which were
      developed more than 40 years ago and present important efficacy and safety
      limitations. Drug repositioning (i.e. finding second or further therapeutic
      indications for known drugs) has raised considerable interest within the
      international drug development community. There are many explanations to the
      current interest on drug repositioning including the possibility to partially
      circumvent clinical trials and the consequent saving in time and resources. It
      has been suggested as a particular attractive approach for the development of
      novel therapeutics for neglected diseases, which are usually driven by public or
      non-profit organizations. Here we review current computer-guided approaches to
      drug repositioning and reports on drug repositioning stories oriented to Chagas
      disease, with a focus on computer-guided drug repositioning campaigns. 

PMID- 25769968
TI  - Enabling virtual screening of potent and safer antimicrobial agents against noma:
      mtk-QSBER model for simultaneous prediction of antibacterial activities and ADMET
      properties.
AB  - Neglected diseases are infections that thrive mainly among underdeveloped
      countries, particularly those belonging to regions found in Asia, Africa, and
      America. One of the most complex diseases is noma, a dangerous health condition
      characterized by a polymicrobial and opportunistic nature. The search for potent
      and safer antibacterial agents against this disease is therefore a goal of
      particular interest. Chemoinformatics can be used to rationalize the discovery of
      drug candidates, diminishing time and financial resources. However, in the case
      of noma, there is no in silico model available for its use in the discovery of
      efficacious antibacterial agents. This work is devoted to report the first mtk
      QSBER model, which integrates dissimilar kinds of chemical and biological data.
      The model was generated with the aim of simultaneously predicting activity
      against bacteria present in noma, and ADMET (absorption, distribution,
      metabolism, elimination, toxicity) parameters. The mtk-QSBER model was
      constructed by employing a large and heterogeneous dataset of chemicals and
      displayed accuracies higher than 90% in both training and prediction sets. We
      confirmed the practical applicability of the model by predicting multiple
      profiles of the investigational antibacterial drug delafloxacin, and the
      predictions converged with the experimental reports. To date, this is the first
      model focused on the virtual search for desirable anti-noma agents. 

PMID- 25769969
TI  - Topoisomerase 1B as a target against leishmaniasis.
AB  - Leishmaniasis affects more than 12 million people in 98 countries, the infection
      being caused by more than 20 species of protozoan parasites belonging to the
      genus Leishmania and spread by sandflies bite. Poor sanitary conditions,
      malnutrition, deforestation and urbanization increase the risk for leishmaniasis.
      Leishmaniasis is the only tropical disease treated with non-anti-leishmanial
      drugs, among which liposomal amphotericin B, a combination of pentavalent
      antimonials and paromomycin and miltefosine, that are highly toxic, represent the
      most used ones. Drug resistance is now widespread and the search for new
      molecular targets is open. Topoisomerase 1B, that controls the topological state
      of DNA and is essential for the parasites viability, has been detected as a
      promising target for anti-leishmaniasis therapy. The enzyme presents
      structural/functional differences with the human counterpart, making it unique
      among Eukarya. Here we review the structural features of this enzyme and the
      drugs that can be developed and used for this specific targeting.

PMID- 25769970
TI  - Functional correlation of medicinal chemistry and Entamoeba histolytica
      treatment: an emphasis on the past, present and future chemotherapy.
AB  - Entamoeba being an internal parasite is the causative organism of many human and
      animal infections with lethal consequences. Chemotherapy against Entamoeba was
      well established by both synthetic and natural products. Vigorous attainments
      were made by different researchers all over the world for discovering better
      chemical entities and the potent formulations. Preexisting compounds were
      developed into non-cytotoxic and with an enhanced therapeutic compounds by usage
      of multiparametric optimization techniques like QSAR, and molecular docking. The
      present review is therefore an aerial perspective of importance of medicinal
      chemistry in anti-amoebic chemotherapy. The review elucidates the existing
      synthetic compounds, their analogues, natural products, in silico studies and
      some novel methods adopted for the drug design as anti-amoebic agents which would
      be of assured benefit in the future drug design. 

PMID- 25769971
TI  - Drug design for neglected disease in Brazil.
AB  - Neglected tropical diseases (NTD) are a group of 17 diseases transmitted by
      virus, protozoa, helminthes and bacteria. These illnesses are responsible for
      millions of deaths per year, affecting mainly the poorest populations in the
      world. The therapeutic drugs available are obsolete, toxic, have questionable
      efficacy and there are reports of resistance. Therefore, the discovery of new,
      safe, effective and affordable active molecules is urgently needed. Considering
      that, the main purpose of this mini-review is to show the current scenario
      concerning drug design for neglected disease in Brazil. NTD are a very broad
      topic. Thus, we selected four infections for discussion: Chagas disease,
      leishmaniasis, malaria and tuberculosis. According to CNPq (National Counsel of
      Technological and Scientific Development) directories, there are many Brazilian
      groups studying these respective diseases. The papers published possess high
      quality and some of them, the most recent, are briefly discussed here. Medicinal
      chemistry approaches such as synthesis of novel series of molecules and
      biological activity evaluation, studies of structure-activity relationships
      (qualitative and quantitative), molecular modeling calculations and
      electrochemistry are some of the tools applied in the design of the compounds. 

PMID- 25769972
TI  - Targeting polyamine metabolism for finding new drugs against leishmaniasis: a
      review.
AB  - Leishmaniasis is a neglected disease affecting more than 12 million people
      worldwide. The most used drugs are pentavalent antimonials that are very toxic
      and display the problem of drug resistance, especially in endemic regions such as
      Bihar in India. For this reason, it is urgent to find new and less toxic drugs
      against leishmaniasis. To this end, the understanding of pathways affecting
      parasite survival is of prime importance for targeted drug discovery. The
      parasite survival inside the macrophage is strongly dependent on polyamine
      metabolism. Polyamines are, in fact, very important for cell growth and
      proliferation. In particular, spermidine (Spd), the final product of the
      polyamine biosynthesis pathway, serves as a precursor for trypanothione (N1,N8-
      bis(glutathionyl)spermidine, T(SH)2) and hypusine (N(epsilon)-(4-amino-2
      hydroxybutyl)lysine). T(SH)2 is a key molecule for parasite defense against the
      hydrogen peroxide produced by macrophages during the infection. Hypusination is a
      posttranslational modification occurring exclusively in the eukaryotic initiation
      factor 5A (eIF5A), which has an important role in avoiding the ribosome stalling
      during the biosynthesis of protein containing polyprolines sequences. The
      enzymes, belonging to the spermidine metabolism, i.e. arginase (ARG), ornithine
      decarboxylase (ODC), S-adenosylmethionine decarboxylase (AdoMetDC), spermidine
      synthase (SpdS), trypanothione synthetase (TryS or TSA), trypanothione reductase
      (TryR or TR), tryparedoxin peroxidase (TXNPx), deoxyhypusine synthase (DHS) and
      deoxyhypusine hydroxylase (DOHH) are promising targets for the development of new
      drugs against leishmaniasis. This minireview furnishes a picture of the
      structural, functional and inhibition studies on polyamine metabolism enzymes
      that could guide the discovery of new drugs against leishmaniasis. 

PMID- 25769973
TI  - In-silico analyses of natural products on leishmania enzyme targets.
AB  - Natural products are compounds that are isolated from plants, provide a variety
      of lead structures for the development of new drugs by the pharmaceutical
      industry. The interest in these substances increases because of their beneficial
      effects on human health, which include antiviral, antiallergic, antiplatelet,
      anti-inflammatory, antitumor, antioxidant, and antiparasitic activities.
      Leishmaniasis is the infection caused by protozoa of the genus Leishmania, which
      affects mainly people who live in poor countries, and can cause chronic fever,
      liver problems, anemia, and other blood problems. Current chemotherapies against
      the disease cause side effects, and are ineffective. There are no vaccines, and
      new chemotherapeutic agents for the treatment of leishmaniasis are greatly
      needed. This work reports on some of the enzymatic targets studied in the
      development of new drugs using natural products as inhibitors for the treatment
      of leishmaniasis. We applied ligand-based-virtual screening using Random Forest,
      associated with structure-based-virtual screening (docking), of a small dataset
      of 683 flavonoids and derivatives from an in-house data bank to select structures
      with potential inhibitory activity against pyruvate kinase, an important enzyme
      in Leishmania mexicana's energy production chemistry. The computer-aided drug
      design studies revealed good results against Leishmaniasis for flavones. 

PMID- 25769974
TI  - Tumor biology in older breast cancer patients--what is the impact on survival
      stratified for guideline adherence? A retrospective multi-centre cohort study of
      5378 patients.
AB  - PURPOSE: The tumor biology of older breast cancer patients (oBCP) is usually less
      aggressive, however applied adjuvant treatment is often less potent resulting in
      an impaired disease free survival and overall survival in this group. This study
      tries to answer the following questions for the biological subtypes of oBCP (70+
      y): METHODS: Between 1992 and 2008 the BRENDA ('BRENDA' = quality of BREast
      caNcer care unDer evidence-bAsed guidelines) study group recorded medical data of
      17 participating certified breast cancer centers in Germany. We performed a
      retrospective multi-center database analysis of 5632 patient records. Guideline
      adherent-treatment (GL+) of oBCP(n = 1918) was compared to GL+ of yBCP(n = 3714).
      RESULTS: OBCP were more likely to have hormone receptor positive (HR+) and
      HER2neu negative (HER2-) breast cancer (77.5% vs 74.5%). The rate of GL- was
      significantly different (p < 0.001) between the age groups and the biological
      subgroups (yBCP vs oBCP: 21.8%vs38.8% (HR+/HER2-); 30.6%vs49.7% (HR+/HER2+);
      23.6%vs69.5% (HR-/HER2+); 31.4%vs67.8% (TNBC)). The survival parameters for
      HR+/HER2- and TNBC were significantly worse in case of GL- regarding
      chemotherapy, and if applicable endocrine therapy. A similar association only
      existed in HR-/HER2+ tumors for GL- for radiotherapy and in HR+/HER2+ tumors for
      chemotherapy. CONCLUSIONS: Beside the significantly different distribution of
      biological subtypes in the age groups there is an association between biological
      subtype, and GL+ influencing survival parameters in oBCP.

PMID- 25769975
TI  - Eating traits questionnaires as a continuum of a single concept. Uncontrolled
      eating.
AB  - Research on eating behaviour has identified several potentially relevant eating
      related traits captured by different questionnaires. Often, these questionnaires
      predict Body Mass Index (BMI), but the relationship between them has not been
      explicitly studied. We studied the unity and diversity of questionnaires
      capturing five common eating-related traits: Power of Food, Eating Impulsivity,
      emotional eating, Disinhibition, and binge eating in women from Estonia (n = 740)
      and Canada (n = 456). Using bifactor analysis, we showed that a) these
      questionnaires are largely explained by a single factor, and b) relative to this
      shared factor, only some questionnaires offered additional variance in predicting
      BMI. Hence, these questionnaires seemed to characterise a common factor, which we
      label Uncontrolled Eating. Item Response Theory techniques were then applied to
      demonstrate that c) within this common factor, the questionnaires could be placed
      on a continuum of Uncontrolled Eating. That is, Eating Impulsivity focused on the
      milder degree, Power of Food Scale, emotional eating scales, and Disinhibition on
      intermediate degrees, and the Binge Eating Scale on the most severe degrees of
      Uncontrolled Eating. In sum, evidence from two samples showed that questionnaires
      capturing five common BMI-related traits largely reflected the same underlying
      latent trait - Uncontrolled Eating. In Estonia, some questionnaires focused on
      different severities of this common construct, supporting a continuum model of
      Uncontrolled Eating. These findings provide a starting point for developing
      better questionnaires of the neurobehavioural correlates of obesity, and provide
      a unifying perspective from which to view the existing literature. R scripts and
      data used for the analysis are provided.

PMID- 25769977
TI  - Digital marketing of unhealthy foods to Australian children and adolescents.
AB  - The emergence of new media-including branded websites, social media and mobile
      applications-has created additional touch points for unhealthy food and beverage
      companies to target children and adolescents. The aim of this study was to
      perform an audit of new media for three top selling food and beverage brands in
      Australia. The top selling brand in three of the most advertised food and
      beverage categories was identified. Facebook, websites and mobile phone
      applications from these three brands were assessed using a combination of
      descriptive analyses and structured data collection during June and July 2013.
      Information on target audience, main focus of the activity, marketing strategies
      employed and connectivity were collected. Promotional activities were assessed
      against industry self-regulatory codes. McDonald's, Coca-Cola and Cadbury Dairy
      Milk were audited, with 21 promotional activities identified. These promotional
      activities appeared to use a number of marketing strategies, with frequent use of
      indirect product association, engagement techniques and branding. We identified
      strategic targeting of both children and adolescents. We found that while all
      promotional activities technically met self-regulatory codes (usually due to
      media-specific age restrictions) a number appeared to employ unhealthy food or
      beverage marketing directed to children. Brands are using engaging content via
      new media aimed at children and adolescents to promote unhealthy food and
      beverages. Given the limitations of self-regulatory codes in the context of new
      media, strategies need to be developed to reduce exposure of children and
      adolescents to marketing of unhealthy food and beverage products via these
      avenues. 

PMID- 25769976
TI  - Geno- and cytotoxicity of salinomycin in human nasal mucosa and peripheral blood
      lymphocytes.
AB  - Salinomycin is usually applied in stock breading but has also been described as a
      promising agent against cancer stem cells (CSC). However, knowledge about the
      toxicity of this ionophor substance is incomplete. The aim of this study was to
      investigate cyto- and genotoxic effects of salinomycin in human non-malignant
      cells. Primary human nasal mucosa cells (monolayer and mini organ cultures) and
      peripheral blood lymphocytes from 10 individuals were used to study the cytotoxic
      effects of salinomycin (0.1-175 MUM) by annexin-propidiumiodide- and MTT-test.
      The comet assay was performed to evaluate DNA damage. Additionally, the secretion
      of interleukin-8 was analyzed by ELISA. Flow cytometry and MTT assay revealed
      significant cytotoxic effects in nasal mucosa cells and lymphocytes at low
      salinomycin concentrations of 10-20 MUM. No genotoxic effects could be observed.
      IL-8 secretion was elevated at 5 MUM. Salinomycin-induced cytotoxic and pro
      inflammatory effects were seen at concentrations relevant for anti-cancer
      treatment. Concurrent to the evaluation of salinomycin application in
      experimental oncology, adverse effects in non-malignant cells need to be
      monitored and reduced as much as possible. Further studies are also warranted to
      evaluate the toxic effects in a variety of human cell systems, e.g., liver,
      kidney and muscle cells.

PMID- 25769978
TI  - Mothers' perceptions of Melbourne InFANT Program: informing future practice.
AB  - Intervention programs to prevent childhood obesity are more likely to be
      successful when mothers are involved and engaged. Yet programs that involve
      mothers do not often employ process evaluation to identify aspects of the
      intervention that participants enjoyed or viewed as useful. The aims of this
      study were to describe how participants of the Melbourne InFANT Program-an early
      childhood obesity prevention intervention-engaged in the program and perceived
      its usefulness. Process evaluation data were collected at multiple time points
      during and after the intervention, using mixed methods drawing upon both
      quantitative and qualitative data. Results from short surveys (n = 271) and
      interview transcripts (n = 26) revealed that the Melbourne InFANT Program was
      perceived as useful and relevant by most (82-93%) participants. The formats
      through which the knowledge and skills were delivered were considered concise and
      effective, and aspects considered particularly useful included group sessions and
      advice on practical strategies to minimize stress around mealtimes. Findings from
      this study are important to inform future practice and the development of
      interventions which are well received by participants. 

PMID- 25769979
TI  - Examining phylogenetic relationships among gibbon genera using whole genome
      sequence data using an approximate bayesian computation approach.
AB  - Gibbons are believed to have diverged from the larger great apes ~16.8 MYA and
      today reside in the rainforests of Southeast Asia. Based on their diploid
      chromosome number, the family Hylobatidae is divided into four genera, Nomascus,
      Symphalangus, Hoolock, and Hylobates. Genetic studies attempting to elucidate the
      phylogenetic relationships among gibbons using karyotypes, mitochondrial DNA
      (mtDNA), the Y chromosome, and short autosomal sequences have been inconclusive .
      To examine the relationships among gibbon genera in more depth, we performed
      second-generation whole genome sequencing (WGS) to a mean of ~15* coverage in two
      individuals from each genus. We developed a coalescent-based approximate Bayesian
      computation (ABC) method incorporating a model of sequencing error generated by
      high coverage exome validation to infer the branching order, divergence times,
      and effective population sizes of gibbon taxa. Although Hoolock and Symphalangus
      are likely sister taxa, we could not confidently resolve a single bifurcating
      tree despite the large amount of data analyzed. Instead, our results support the
      hypothesis that all four gibbon genera diverged at approximately the same time.
      Assuming an autosomal mutation rate of 1 * 10(-9)/site/year this speciation
      process occurred ~5 MYA during a period in the Early Pliocene characterized by
      climatic shifts and fragmentation of the Sunda shelf forests. Whole genome
      sequencing of additional individuals will be vital for inferring the extent of
      gene flow among species after the separation of the gibbon genera.

PMID- 25769980
TI  - Cis- and trans-regulatory mechanisms of gene expression in the ASJ sensory neuron
      of Caenorhabditis elegans.
AB  - The identity of a given cell type is determined by the expression of a set of
      genes sharing common cis-regulatory motifs and being regulated by shared
      transcription factors. Here, we identify cis and trans regulatory elements that
      drive gene expression in the bilateral sensory neuron ASJ, located in the head of
      the nematode Caenorhabditis elegans. For this purpose, we have dissected the
      promoters of the only two genes so far reported to be exclusively expressed in
      ASJ, trx-1 and ssu-1. We hereby identify the ASJ motif, a functional cis
      regulatory bipartite promoter region composed of two individual 6 bp elements
      separated by a 3 bp linker. The first element is a 6 bp CG-rich sequence that
      presumably binds the Sp family member zinc-finger transcription factor SPTF-1.
      Interestingly, within the C. elegans nervous system SPTF-1 is also found to be
      expressed only in ASJ neurons where it regulates expression of other genes in
      these neurons and ASJ cell fate. The second element of the bipartite motif is a 6
      bp AT-rich sequence that is predicted to potentially bind a transcription factor
      of the homeobox family. Together, our findings identify a specific promoter
      signature and SPTF-1 as a transcription factor that functions as a terminal
      selector gene to regulate gene expression in C. elegans ASJ sensory neurons.

PMID- 25769983
TI  - A qualitative study exploring the benefits of hospital admissions from the
      perspectives of patients with palliative care needs.
AB  - BACKGROUND: The acute hospital plays a significant role in caring for people with
      a life-limiting illness. Most research to date has focused exclusively upon the
      negative aspects of hospitalisation. Currently, there is little known about the
      benefits of hospital admissions for patients with palliative care needs. AIM: The
      aim of this study was to explore the benefits of hospital admissions, from the
      perspectives of patients with palliative care needs. DESIGN: A qualitative study
      design was adopted. Longitudinal, semi-structured, face-to-face interviews were
      used to elicit the views of patients admitted to hospital in one large urban
      acute hospital in New Zealand. SETTING/PARTICIPANTS: The study sample comprised
      14 patients admitted to Auckland City Hospital between July 2013 and March 2014
      who met one of the Gold Standard Framework Prognostic Indicators for palliative
      care need. RESULTS: Through a process of thematic analysis, four themes were
      identified from the data: being cared for and feeling safe, receiving care to
      manage at home, relief for family and 'feeling better and/or getting better'. The
      benefits of being in hospital were reported to extend beyond treatments received.
      Most participants reported their preference was to come to hospital even if they
      had been able to access the care they received in hospital at home. CONCLUSION:
      This research contributes to a greater understanding of the benefits associated
      with hospitalisation for patients with palliative care needs. The findings
      suggest that such benefits extend beyond the treatment patients receive and
      challenge current assumptions regarding the role of the acute hospital in
      palliative care.

PMID- 25769982
TI  - A single gene causes an interspecific difference in pigmentation in Drosophila.
AB  - The genetic basis of species differences remains understudied. Studies in insects
      have contributed significantly to our understanding of morphological evolution.
      Pigmentation traits in particular have received a great deal of attention and
      several genes in the insect pigmentation pathway have been implicated in inter-
      and intraspecific differences. Nonetheless, much remains unknown about many of
      the genes in this pathway and their potential role in understudied taxa. Here we
      genetically analyze the puparium color difference between members of the virilis
      group of Drosophila. The puparium of Drosophila virilis is black, while those of
      D. americana, D. novamexicana, and D. lummei are brown. We used a series of
      backcross hybrid populations between D. americana and D. virilis to map the
      genomic interval responsible for the difference between this species pair. First,
      we show that the pupal case color difference is caused by a single Mendelizing
      factor, which we ultimately map to an ~11-kb region on chromosome 5. The mapped
      interval includes only the first exon and regulatory region(s) of the dopamine N
      acetyltransferase gene (Dat). This gene encodes an enzyme that is known to play a
      part in the insect pigmentation pathway. Second, we show that this gene is highly
      expressed at the onset of pupation in light brown taxa (D. americana and D.
      novamexicana) relative to D. virilis, but not in the dark brown D. lummei.
      Finally, we examine the role of Dat in adult pigmentation between D. americana
      (heavily melanized) and D. novamexicana (lightly melanized) and find no
      discernible effect of this gene in adults. Our results demonstrate that a single
      gene is entirely or almost entirely responsible for a morphological difference
      between species.

PMID- 25769981
TI  - Identification of AGO3-associated miRNAs and computational prediction of their
      targets in the green alga Chlamydomonas reinhardtii.
AB  - The unicellular green alga Chlamydomonas reinhardtii harbors many types of small
      RNAs (sRNAs) but little is known about their role(s) in the regulation of
      endogenous genes and cellular processes. To define functional microRNAs (miRNAs)
      in Chlamydomonas, we characterized sRNAs associated with an argonaute protein,
      AGO3, by affinity purification and deep sequencing. Using a stringent set of
      criteria for canonical miRNA annotation, we identified 39 precursor miRNAs, which
      produce 45 unique, AGO3-associated miRNA sequences including 13 previously
      reported miRNAs and 32 novel ones. Potential miRNA targets were identified based
      on the complementarity of miRNAs with candidate binding sites on transcripts and
      classified, depending on the extent of complementarity, as being likely to be
      regulated through cleavage or translational repression. The search for cleavage
      targets identified 74 transcripts. However, only 6 of them showed an increase in
      messenger RNA (mRNA) levels in a mutant strain almost devoid of sRNAs. The search
      for translational repression targets, which used complementarity criteria more
      stringent than those empirically required for a reduction in target protein
      levels, identified 488 transcripts. However, unlike observations in metazoans,
      most predicted translation repression targets did not show appreciable changes in
      transcript abundance in the absence of sRNAs. Additionally, of three candidate
      targets examined at the protein level, only one showed a moderate variation in
      polypeptide amount in the mutant strain. Our results emphasize the difficulty in
      identifying genuine miRNA targets in Chlamydomonas and suggest that miRNAs, under
      standard laboratory conditions, might have mainly a modulatory role in endogenous
      gene regulation in this alga.

PMID- 25769984
TI  - NICE recommends small improvements to help people stay at healthy weight.

PMID- 25769985
TI  - Unorganized prostate-specific antigen-based screening for prostate cancer: more
      harm than benefit. When will we finally start to implement guidelines and risk
      assessment tools in clinical practice?

PMID- 25769986
TI  - Future-proofing Gleason Grading: What to Call Gleason 6 Prostate Cancer?
AB  - At the 2014 International Society of Urological Pathology meeting, changes to
      prostate cancer grading were discussed including new prognostic Gleason grade
      groups 1-5 representing Gleason scores of 3+3, 3+4, 4+3, 8, and 9-10,
      respectively. 

PMID- 25769987
TI  - Threat of infectious diseases comes and goes; fundamental challenges remain.

PMID- 25769989
TI  - Editor's Note regarding the on-line position paper, "Ethical issues in the
      response to Ebola virus disease in US emergency departments: a position paper of
      the American College of Emergency Physicians, the Emergency Nurses Association
      and the Society for Academic Emergency Medicine".

PMID- 25769990
TI  - Health care-associated infections (HAIs).

PMID- 25769991
TI  - Aid and attendance.

PMID- 25769992
TI  - Respect for the mass casualty incident in Aurora.

PMID- 25769993
TI  - Response.

PMID- 25769994
TI  - Trending now: re-emerging infectious disease update.

PMID- 25769995
TI  - Bacterial tracheitis in a 9-month-old child.

PMID- 25769996
TI  - Pediatric shock.

PMID- 25769997
TI  - Standardizing the care of occupational blood-borne pathogen exposures to reduce
      unnecessary use of the emergency department.
AB  - PROBLEM: Care of health care workers with a blood-borne pathogen (BBP) exposure
      who seek treatment in emergency departments needs to be standardized. A
      standardized system may lead to better care for exposed individuals. METHODS: An
      interprofessional process was developed to standardize care of occupational BBP
      exposures in nonemployees. A health planning program design was conducted to
      compare outcomes before and after the standardized process was enacted. RESULTS:
      Standardizing treatment of occupational exposures provided more efficient care
      for exposed nonemployee workers and allowed an improved use of ED resources.
      IMPLICATIONS FOR PRACTICE: Programs developed to improve utilization of the
      emergency department have a greater chance of success when developed using an
      interprofessional, collaborative approach.

PMID- 25769998
TI  - Emergency nursing review questions: March 2015.
AB  - The review questions that are featured in each of the issues of the JEN are based
      on the Emergency Nursing Core Curriculum and other pertinent resources to
      emergency nursing practice, pediatric and adult. These questions offer emergency
      nurses an opportunity to test their knowledge about their practice. These
      questions appear both in print and online. 

PMID- 25769999
TI  - The Netherlands: well prepared for an outbreak of Ebola virus.

PMID- 25770000
TI  - Pediatric infectious diseases.

PMID- 25770001
TI  - ED Ebola triage algorithm: a tool and process for compliance.

PMID- 25770002
TI  - Arterial blood gas review.

PMID- 25770003
TI  - Ethical issues in the response to Ebola virus disease in US emergency
      departments: a position paper of the American College of Emergency Physicians,
      the Emergency Nurses Association and the Society for Academic Emergency Medicine.
AB  - The 2014 outbreak of Ebola Virus Disease (EVD) in West Africa has presented a
      significant public health crisis to the international health community and
      challenged US emergency departments to prepare for patients with a disease of
      exceeding rarity in developed nations. With the presentation of patients with
      Ebola to US acute care facilities, ethical questions have been raised in both the
      press and medical literature as to how US emergency departments, emergency
      physicians, emergency nurses and other stakeholders in the healthcare system
      should approach the current epidemic and its potential for spread in the domestic
      environment. To address these concerns, the American College of Emergency
      Physicians, the Emergency Nurses Association and the Society for Academic
      Emergency Medicine developed this joint position paper to provide guidance to US
      emergency physicians, emergency nurses and other stakeholders in the healthcare
      system on how to approach the ethical dilemmas posed by the outbreak of EVD. This
      paper will address areas of immediate and potential ethical concern to US
      emergency departments in how they approach preparation for and management of
      potential patients with EVD. 

PMID- 25770004
TI  - The role of high loop gain induced by intermittent hypoxia in the pathophysiology
      of obstructive sleep apnea.

PMID- 25770005
TI  - Are first ventilatory threshold and 6-minute walk test heart rate
      interchangeable? A pilot study in healthy elderlies and cardiac patients.
AB  - BACKGROUND: Heart rate (HR) at the ventilatory threshold (VT) is often used to
      prescribe exercise intensity in cardiac rehabilitation. Some studies have
      reported no significant difference between HR at VT and HR measured at the end of
      a 6-min walk test (6-MWT) in cardiac patients. The aim of this work was to assess
      the potential equivalence between those parameters at the individual level.
      METHOD: Three groups of subjects performed a stress test and a 6-MWT: 22 healthy
      elderlies (GES, 77 +/- 3.7 years), 10 stable coronary artery disease (CAD)
      patients (GMI, 50.9 +/- 4.2 years) and 30 patients with chronic heart failure
      (GHF, 63.3 +/- 10 years). We analyzed the correlation, mean bias, 95% confidence
      interval (95% CI) of the mean bias and the magnitude of the bias between 6-MWT-HR
      and VT-HR. RESULTS: There was a significant difference between 6-MWT and VT-HR in
      GHF (99.1 +/- 8.8 vs 91.6 +/- 18.6 bpm, P=0.016) but not in GES and GMI. The
      correlation between those 2 parameters was high for GMI (r=0.78, P<0.05), and
      moderate for GES and GHF (r=0.48 and 0.55, respectively, P<0.05). The 95% CI of
      bias was large (>30%) in GES and GHF and acceptable in GMI (8-12%). CONCLUSION: 6
      MWT-HR and VT-HR do not appear interchangeable at the individual level in healthy
      elderlies and CHF patients. In CAD patients, further larger studies and/or the
      development of other walk tests could help in confirming the interest of a
      training prescription based on walking performance, after an exhaustive study of
      their cardiometabolic requirements.

PMID- 25770006
TI  - Training evaluation for a practice in spasticity-related techniques.

PMID- 25770007
TI  - Checklists to manage pain induced by exercise and mobilization (PIEM) during
      physical therapy programs: PIEM checklists for practitioners and
      physiotherapists.
AB  - OBJECTIVES: Identify key informational and educational items ("messages") to
      provide to physicians (general practitioners and specialists) and
      physiotherapists for the management of pain induced by exercise and mobilization
      (PIEM). Develop checklists to improve this management in daily practice. MATERIAL
      AND METHODS: The Delphi method for consensus-building was used to identify
      informational and educational messages for health professionals who deal with
      PIEM. Informed by the results of an extensive qualitative study, a panel of
      experts from 5 medical and paramedical disciplines concerned with PIEM and a
      representative of a patients' association were interviewed individually and
      iteratively in order to obtain a single, convergent opinion. RESULTS: Delphi
      consultation helped to determine 9 areas corresponding to 54 key messages of
      information and education for doctors and physiotherapists who deal with PIEM.
      These messages relate to: defining, characterizing, identifying, and evaluating
      PIEM; identifying factors that may cause or increase this pain; informing the
      patient in order to avoid misinterpretation of PIEM; preventing and treating
      PIEM; and dealing with it during physical therapy sessions. The method also
      enabled us to develop 2 synthetic instruments (checklists) - 1 for physicians and
      1 for physiotherapists - to help with the management of this pain. CONCLUSION:
      Consulting a panel of experts comprising different categories of actors dealing
      with PIEM on the basis of a thorough qualitative diagnosis in order to identify
      messages for a training program makes it possible to harmonize programs with the
      expectations of patients and the problems encountered by professionals. The
      formulation of this program and the institutionalization of two checklists should
      enable health professionals to identify, qualify, and deal more effectively with
      PIEM.

PMID- 25770009
TI  - Synthesis, characterization, X-ray crystal structure, DFT calculation and
      antibacterial activities of new vanadium(IV, V) complexes containing chelidamic
      acid and novel thiourea derivatives.
AB  - Three new thiourea ligands derived from the condensation of aroyl- and aryl
      isothiocyanate derivatives with 2,6-diaminopyridine, named 1,1'-(pyridine-2,6
      diyl)bis(3-(benzoyl)thiourea) (L1), 1,1'-(pyridine-2,6-diyl)bis(3-(2
      chlorobenzoyl)thiourea) (L2) and 1,1'-(pyridine-2,6-diyl)bis(3-(4
      chlorophenyl)thiourea) (L3), their oxido-vanadium(IV) complexes, namely
      [VO(L1('))(H2O)] (C1), [VO(L2('))(H2O)] (C2) and [VO(L3('))(H2O)] (C3), and also,
      dioxo-vanadium(V) complex containing 4-hydroxy-2,6-pyridine dicarboxylic acid
      (chelidamic acid, H2dipic-OH) and metformin (N,N-dimethylbiguanide, Met), named
      [H2Met][VO2(dipic-OH)]2.H2O (C4), were synthesized and characterized by elemental
      analysis, FTIR and (1)H NMR and UV-visible spectroscopies. Proposed structures
      for free thiourea ligands and their vanadium complexes were corroborated by
      applying geometry optimization and conformational analysis. Solid state structure
      of complex [H2Met][VO2(dipic-OH)]2.H2O (triclinic, Pi) was fully determined by
      single crystal X-ray diffraction analysis. In this complex, metformin is double
      protonated and acted as counter ion. The antibacterial properties of these
      compounds were investigated in vitro against standard Gram-positive and Gram
      negative bacterial strains. The experiments showed that vanadium(IV) complexes
      had the superior antibacterial activities than novel thiourea derivatives and
      vanadium(V) complex against all Gram-positive and Gram-negative bacterial
      strains. 

PMID- 25770008
TI  - [Oral anticogulation for non-valvular atrial fibrilation in the elderly].
AB  - Anticoagulation in elderly people with non-valvular atrial afibrillation (AF) is
      a challenge, due to the thromboembolic, as well as the haemorrhagic risks. The
      correct use of anticoagulants in these patients has shown a higher net clinical
      benefit when comparing it with a younger population. Non-vitamin K antagonist
      oral anticoagulants (NOACs) have been compared to oral vitamin K antagonists in
      several studies that included a sufficient number of elderly people. Favourable
      results for non-vitamin K antagonist oral anticoagulants were obtained in these
      studies, making them the preferred treatment for this group of patients. Basing
      the estimations on indirect comparisons, the ideal anticoagulant and the specific
      dose for each particular case has been determined. Finally, a new algorithm has
      been developed that relates these parameters. Geriatric assessment is the key to
      the indication for an anticoagulation, the type of anticoagulant needed, and also
      the best way to optimise all the factors for a safe anticoagulation. The arrival
      of non-vitamin K antagonist oral anticoagulants will enhance the efficient
      thromboembolic prophylaxis rate in elderly people with AF. This new treatment
      will remove different controversial prophylaxis, such as antiaggregants. 

PMID- 25770010
TI  - Sunflower metallothionein family characterisation. Study of the Zn(II)- and
      Cd(II)-binding abilities of the HaMT1 and HaMT2 isoforms.
AB  - Plant metallothioneins (MTs) constitute a family of small Cys-rich proteins
      capable of coordinating metal ions, significantly differing from microbial and
      animal MTs. They are divided into four subfamilies depending on the Cys pattern
      in their sequence. In this work, the MT system of the sunflower plant (Helianthus
      annuus) has been defined, with ten genes coding for MTs (HaMT) belonging to the
      four plant MT subfamilies; three HaMT1, four HaMT2, one HaMT3 and two HaMT4
      isoforms. The gene expression pattern and capacity to confer metal resistance to
      yeast cells have been analysed for at least one member of each subfamily. The
      divalent metal ion-binding abilities of HaMT1-2 and HaMT2-1 (the isoforms encoded
      by the most abundantly expressed HaMT1 and HaMT2 isogenes) have been
      characterised, as HaMT3 and HaMT4 were previously studied. Those isoforms
      constitute an optimum material to study the effect of Cys number variability on
      their coordination abilities, as they exhibit additional Cys residues regarding
      the canonical Cys pattern of each subfamily. Our results show that the variation
      in the number of Cys does not drastically modify their M(II)-binding abilities,
      but instead modulates the degree of heterogeneity of the corresponding
      recombinant syntheses. Significantly, the Zn(II)-HaMT1 complexes were highly
      susceptible to proteolytic cleavage. The recombinant Cd-MT preparations of both
      isoforms exhibit significant acid-labile sulphide content-Cd6S8 or Cd7S7 species.
      Overall results suggest that HaMT2-1 is probably associated with Cd(II)
      detoxification, in contrast to HaMT1-2, which may be more related to
      physiological functions, such as metal ion transport and delivery. 

PMID- 25770012
TI  - TMEM16A mediates the hypersecretion of mucus induced by Interleukin-13.
AB  - Previous studies showed that the Ca(2+)-activated Cl(-) channel (CaCC) was
      involved in the pathogenesis of mucus hypersecretion induced by Interleukin-13
      (IL-13). However, the mechanisms underlying the process were unknown. Recently,
      transmembrane protein 16A (TMEM16A) was identified as the channel underlying the
      CaCC current. The aim of the current study was to investigate whether the TMEM16A
      channel is part of the mechanism underlying IL-13-induced mucus hypersecretion.
      We observed that both TMEM16A mRNA and protein expression were significantly up
      regulated after treatment with IL-13 in human bronchial epithelial 16 (HBE 16)
      cells, which correlated with an increase in mucus production. Additionally, mucus
      hypersecretion in rat airways was induced by intratracheal instillation of IL-13
      and similar increases were observed in the expression of TMEM16A mRNA and protein
      in the bronchial epithelium. Niflumic acid (NA), a selective antagonist of CaCC,
      markedly blocked IL-13-induced mucin (MUC) 5AC mRNA and protein production in
      vivo and in vitro. Further investigation with HBE16 cells revealed that TMEM16A
      overexpression clearly promoted mucus production, IkappaBalpha phosphorylation,
      and p65 accumulation in the nucleus. The loss of TMEM16A resulted in inhibition
      of mucus production, and the TMEM16A-mediated production of MUC5AC was
      significantly blocked by a nuclear factor-kappa B (NF-kappaB) inhibitor.
      Therefore, the TMEM16A channel acts upstream of NF-kappaB in the regulation of
      mucus production. This is the first demonstration that the TMEM16A-NF-kappaB
      pathway is positively involved in IL-13-induced mucus production, which provides
      novel insight into the molecular mechanism of mucin overproduction. 

PMID- 25770011
TI  - Revisiting the sphingolipid rheostat: Evolving concepts in cancer therapy.

PMID- 25770013
TI  - Local dominance of exotic plants declines with residence time: a role for plant
      soil feedback?
AB  - Recent studies have shown that introduced exotic plant species may be released
      from their native soil-borne pathogens, but that they become exposed to increased
      soil pathogen activity in the new range when time since introduction increases.
      Other studies have shown that introduced exotic plant species become less
      dominant when time since introduction increases, and that plant abundance may be
      controlled by soil-borne pathogens; however, no study yet has tested whether
      these soil effects might explain the decline in dominance of exotic plant species
      following their initial invasiveness. Here we determine plant-soil feedback of 20
      plant species that have been introduced into The Netherlands. We tested the
      hypotheses that (i) exotic plant species with a longer residence time have a more
      negative soil feedback and (ii) greater local dominance of the introduced exotic
      plant species correlates with less negative, or more positive, plant-soil
      feedback. Although the local dominance of exotic plant species decreased with
      time since introduction, there was no relationship of local dominance with plant
      soil feedback. Plant-soil feedback also did not become more negative with
      increasing time since introduction. We discuss why our results may deviate from
      some earlier published studies and why plant-soil feedback may not in all cases,
      or not in all comparisons, explain patterns of local dominance of introduced
      exotic plant species. 

PMID- 25770014
TI  - A meta-analysis of induction therapy for advanced thymic epithelial tumors.
AB  - This meta-analysis was designed to determine the effect of induction therapy and
      surgical resection on overall survival in patients with advanced thymic
      epithelial tumors. PubMed and Scopus databases were queried, and 12 studies
      comprising 266 patients were analyzed. Meta-analysis using a random effect model
      revealed a pooled rate of response to induction therapy of 59%, a pooled rate of
      complete resection of 73%, and pooled 5-year and 10-year overall survival of 87%
      and 76% after induction therapy, respectively. Surgical resection after induction
      therapy for advanced thymic epithelial tumors can be undertaken with favorable
      outcomes.

PMID- 25770015
TI  - Apple software will allow researchers to gather health data from iPhones.

PMID- 25770016
TI  - Easily manoeuvrable osteotome for pterygomaxillary disjunction.

PMID- 25770017
TI  - Re: Limited mouth opening of unknown cause cured by diagnostic coronoidectomy: a
      new clinical entity? Br J Oral Maxillofac Surg 2015:53(3):230-4.

PMID- 25770018
TI  - Peak inflammation in atherosclerosis, primary biliary cirrhosis and autoimmune
      arthritis is counter-intuitively associated with regulatory T cell enrichment.
AB  - Regulatory T cells (Treg) influence the development of autoimmunity and their use
      is increasingly proposed for clinical applications. The well-characterized
      suppressive potential of Treg frequently leads to the assumption that Treg
      presence in prevailing numbers is indicative of immunosuppression. We
      hypothesized that this assumption may be false. We examined models of three
      different diseases caused by organ-specific autoimmune responses: primary biliary
      cirrhosis, atherosclerosis and rheumatoid arthritis (RA). We examined indicators
      of relative abundance of Treg compared to pro-inflammatory T cells, during peak
      inflammation. In all cases, the results were compatible with a relative
      enrichment of Treg at the site of inflammation or its most proximal draining
      lymph node. Conversely, in healthy mice or mice successfully protected from
      disease via a Treg-mediated mechanism, the data did not suggest that any Treg
      accumulation was occurring. This counter-intuitive finding may appear to be at
      odds with the immunosuppressive nature of Treg. Yet extensive previous studies in
      RA show that an accumulation of Treg occurs at peak inflammation, albeit without
      resulting in suppression, as the Treg suppressive function is overcome by the
      cytokine-rich environment. We suggest that this is a ubiquitous feature of
      autoimmune inflammation. Treg abundance in patient samples is increasingly used
      as an indicator of a state of immunosuppression. We conclude that this strategy
      should be revisited as it may potentially be a source of misinterpretation. 

PMID- 25770019
TI  - Expression of CD73 and A2A receptors in cells from subjects with obesity and type
      2 diabetes mellitus.
AB  - Regulatory T cells have various mechanisms to suppress the inflammatory response,
      among these, the modulation of the microenvironment through adenosine and with
      the participation of CD39, CD73 and A2A. The aim of this study was to assess the
      expression of CD73 and A2A in immune cells and the effect of activation of A2A by
      an adenosine analogue on apoptosis in patients with obesity and type 2 diabetes
      mellitus (T2D). CD73 and A2A expression were analyzed by flow cytometry in
      lymphocyte subpopulations from patients with obesity (n = 22), T2D (n = 22), and
      healthy subjects (n = 20). Lymphocytes were treated with the selective A2A
      antagonist (ZM241385) or the selective A2A agonist (CGS21680), and apoptotic
      cells were detected by Annexin V. We found an increased expression of CD39
      coupled to a decrease in CD73 in the patient groups with obesity and T2D compared
      to the control group in the different studied lymphocyte subpopulations. A2A
      expression was found to be increased in different subpopulations of lymphocytes
      from T2D patients. We also detected positive correlations between CD39+ cells and
      age and BMI. Meanwhile, CD73+ cells showed negative correlations with age, WHR,
      BMI, FPG, HbAc1, triglycerides and cholesterol. Moreover, an increase in the
      percentage of apoptotic cells from T2D patients with regard to the groups with
      obesity and control was observed. In addition, the CD8+ T cells of patients with
      T2D exhibited decreased apoptosis when treated with the A2A agonist. In
      conclusion, our data suggest a possible role for CD73 and A2A in inflammation
      observed in patients with T2D and obesity mediated via apoptosis.

PMID- 25770020
TI  - Demand-side strategies to deal with moral hazard in public insurance for long
      term care.
AB  - Moral hazard in public insurance for long-term care may be counteracted by
      strategies influencing supply or demand. Demand-side strategies may target the
      patient or the insurer. Various demand-side strategies and how they are
      implemented in four European countries (Germany, Belgium, Switzerland and the
      Netherlands) are described, highlighting the pros and cons of each strategy.
      Patient-oriented strategies to counteract moral hazard are used in all four
      countries but their impact on efficiency is unclear and crucially depends on
      their design. Strategies targeted at insurers are much less popular: Belgium and
      Switzerland have introduced elements of managed competition for some types of
      long-term care, as has the Netherlands in 2015. As only some elements of managed
      competition have been introduced, it is unclear whether it improves efficiency.
      Its effect will depend on the feasibility of setting appropriate financial
      incentives for insurers using risk equalization and the willingness of
      governments to provide insurers with instruments to manage long-term care. 

PMID- 25770021
TI  - Value of shear-wave elastography in the diagnosis of symptomatic invasive lobular
      breast cancer.
AB  - AIM: To investigate the contribution of shear-wave elastography (SWE) in
      diagnosing invasive lobular breast cancer (ILC) in symptomatic patients.
      MATERIALS AND METHODS: A retrospective case-controlled study of 52 patients with
      ILC and 52 patients with invasive ductal cancer (IDC), matched for age and tumour
      size, was performed. Breast density and mammographic and greyscale ultrasound
      features were graded using Breast Imaging-Reporting and Data System (BI-RADS)
      classification by two radiologists, blinded to SWE and pathology findings. Forty
      four benign lesions were also included. The sensitivity of SWE was assessed,
      using a cut-off value of 50 kPa for mean elasticity. Statistical significance was
      evaluated using Chi-square and Chi-square for trend tests. RESULTS: Mean age for
      both ILC and IDC groups was 67 years. Mean size for ILC was 44 mm and IDC was 37
      mm. The sensitivity for detection of ILC and IDC for mammography, greyscale
      ultrasound, and SWE were 79% versus 87%, 87% versus 98%, 94% versus 100%,
      respectively. SWE had significantly higher sensitivities than mammography for the
      detection of both ILC and IDC (p = 0.012 and p = 0.001, respectively). SWE was
      not significantly more sensitive than greyscale ultrasound for the detection of
      either tumour type. Four (8%) lobular cancers were benign/normal at both
      mammography and greyscale ultrasound, but suspicious on SWE. The incremental gain
      in sensitivity by using SWE in ILC was statistically significant compared to IDC
      (p = 0.01). CONCLUSION: SWE can diagnose lobular cancers that have benign/normal
      findings on conventional imaging as suspicious.

PMID- 25770022
TI  - Patterns of spread of head and neck adenoid cystic carcinoma.
AB  - We present a review of head and neck adenoid cystic carcinoma (ACC). Imaging
      features of the primary tumour, patterns of locoregional spread, and distant
      metastasis with emphasis on perineural extension and imaging pitfalls are
      discussed with illustrated examples. 

PMID- 25770023
TI  - The forgotten tragedy of unidentified dead in the Mediterranean.
AB  - The need to identify the dead - an issue of paramount importance for the forensic
      sciences - and its importance for humanitarian, administrative, judicial and
      other purposes are universal values enshrined by domestic and international law.
      However, for hundreds of men, women and children, migrants, who die every year in
      their attempt to cross the Mediterranean Sea to reach Europe this fundamental
      right remains unfulfilled. In order to address and bring solutions to this
      tragedy the International Committee of the Red Cross (ICRC) carried out an
      assessment in 2012 and 2013 across European Mediterranean countries affected by
      irregular immigration across the sea (Italy, Greece, Malta, Portugal, France,
      Spain). An international meeting in 2013 among Southern European countries led to
      recommendations which should serve as a road-map for action. They are already
      guiding activities of the ICRC and other participant institutions. The Council of
      Europe, which endorsed the recommendations, has since stepped up its efforts to
      prevent and resolve the humanitarian consequences of migration, including the
      unidentified dead. Among other things it has called on its Member States to "set
      up a proper system of data collection of the mortal remains of people who lose
      their lives in the Mediterranean and make it swiftly accessible to relatives". 

PMID- 25770024
TI  - Race-ethnic and sex differences in left ventricular structure and function: the
      Coronary Artery Risk Development in Young Adults (CARDIA) Study.
AB  - BACKGROUND: We investigated race-ethnic and sex-specific relationships of left
      ventricular (LV) structure and LV function in African American and white men and
      women at 43 to 55 years of age. METHODS AND RESULTS: The Coronary Artery Risk
      Development in Young Adults (CARDIA) Study enrolled African American and white
      adults, age 18 to 30 years, from 4 US field centers in 1985-1986 (Year-0) who
      have been followed prospectively. We included participants with echocardiographic
      assessment at the Year-25 examination (n=3320; 44% men, 46% African American).
      The end points of LV structure and function were assessed using conventional
      echocardiography and speckle-tracking echocardiography. In the multivariable
      models, we used, in addition to race-ethnic and gender terms, demographic (age,
      physical activity, and educational level) and cardiovascular risk variables (body
      mass index, systolic blood pressure, diastolic blood pressure, heart rate,
      presence of diabetes, use of antihypertensive medications, number of
      cigarettes/day) at Year-0 and -25 examinations as independent predictors of
      echocardiographic outcomes at the Year-25 examination (LV end-diastolic volume
      [LVEDV]/height, LV end-systolic volume [LVESV]/height, LV mass [LVM]/height, and
      LVM/LVEDV ratio for LV structural indices; LV ejection fraction [LVEF], Ell, and
      Ecc for systolic indices; and early diastolic and atrial ratio, mitral annulus
      early peak velocity, ratio of mitral early peak velocity/mitral annulus early
      peak velocity; ratio, left atrial volume/height, longitudinal peak early
      diastolic strain rate, and circumferential peak early diastolic strain rate for
      diastolic indices). Compared with women, African American and white men had
      greater LV volume and LV mass (P<0.05). For LV systolic function, African
      American men had the lowest LVEF as well as longitudinal (Ell) and
      circumferential (Ecc) strain indices among the 4 sex/race-ethnic groups (P<0.05).
      For LV diastolic function, African American men and women had larger left atrial
      volumes; African American men had the lowest values of Ell and Ecc for diastolic
      strain rate (P<0.05). These race/sex differences in LV structure and LV function
      persisted after adjustment. CONCLUSIONS: African American men have greater LV
      size and lower LV systolic and diastolic function compared to African American
      women and to white men and women. The reasons for these racial-ethnic differences
      are partially but not completely explained by established cardiovascular risk
      factors.

PMID- 25770026
TI  - [Giant osteolytic lesions of the mandible in children].

PMID- 25770025
TI  - Dipeptidyl-peptidase-4 inhibitor, alogliptin, attenuates arterial inflammation
      and neointimal formation after injury in low-density lipoprotein (LDL) receptor
      deficient mice.
AB  - BACKGROUND: The results of recent studies suggest that dipeptidyl-peptidase-4
      inhibitors have antiatherogenic effects. However, whether or not dipeptidyl
      peptidase-4 inhibitors could suppress arterial inflammation and intimal
      hyperplasia after injury remains undetermined. The present study aims to clarify
      the anti-inflammatory effects of the dipeptidyl-peptidase-4 inhibitor, alogliptin
      (AGP), on the arteries of atherogenic low-density lipoprotein receptor-deficient
      (LKO) mice. METHODS AND RESULTS: We compared intimal hyperplasia in LKO mice 2
      weeks after femoral artery injury using an external vascular cuff model. All mice
      received oral injection of AGP (20 mg/kg per day) or normal saline (control) once
      daily for 14 days. Fasting blood sugar levels, serum cholesterol levels, or blood
      pressure did not significantly differ between the 2 groups. Plasma levels of
      active glucagon-like peptide-1 were higher in the AGP than in the control LKO
      mice (22.2+/-1.9 versus 15.6+/-0.9 pg/mL; P<0.05). Compared with saline, AGP
      significantly reduced intimal hyperplasia (1087+/-127 versus 1896+/-140 MUm(2);
      P<0.001) as well as the intima/media ratio (0.08+/-0.01 versus 0.16+/-0.02;
      P<0.001). Immunostaining showed that AGP reduced proliferating cells
      (proliferating cell nuclear antigen-positive nuclei; P<0.001), percent smooth
      muscle cell area (alpha-SMA-positive cells; P<0.001), inflammatory cells
      infiltration (lymphocyte antigen 6 complex-positive cells; P<0.05), tumor
      necrosis factor-alpha expression (P<0.05), and percent phospho-NF-kappaB-positive
      cell compared with saline. Levels of tumor necrosis factor -alpha (0.5-fold
      P<0.05), monocyte chemoattractant protein 1 (0.3-fold P<0.01), and interleukin
      1beta (0.2-fold P<0.05) mRNA were lower in the injured arteries of the AGP than
      in the control group. CONCLUSIONS: AGP appeared to suppress neointimal formation
      by inhibiting inflammation, independently of its effects on glucose or
      cholesterol metabolism in atherogenic LKO mice.

PMID- 25770027
TI  - [Orthopantomogram showing a coronoid process osteolysis].

PMID- 25770028
TI  - Catamenial epilepsy: Update on prevalence, pathophysiology and treatment from the
      findings of the NIH Progesterone Treatment Trial.
AB  - PURPOSE: To extend our knowledge and practical application of the concept of
      catamenial epilepsy. METHODS: The review focuses on the impact of the NIH
      Progesterone Trial on our understanding of the pathophysiology and treatment of
      catamenial epilepsy. RESULTS: Catamenial epilepsy refers to the cyclic
      exacerbation of seizures in relation to the menstrual cycle. An interaction
      between seizures and the menstrual cycle is suggested by variations in seizure
      frequency according to the day, phase and ovulatory status of the menstrual
      cycle. There are three commonly recognized patterns: perimenstrual (C1: Day -3 to
      +3), peri-ovulatory (C2: Day 10 to 3) and entire luteal phase in anovulatory
      cycles (C3: Day 10 to 3). Pathophysiological determinants include 1) the
      neuroactive properties of reproductive steroids, 2) the variation of neuroactive
      steroid levels across the menstrual cycle and 3) the differential susceptibility
      of epileptic substrates to neuroactive steroid effects. Perimenstrual seizure
      exacerbation may result from the premenstrual withdrawal of progesterone which is
      accompanied by withdrawal of allopregnanolone, a potent positive allosteric
      modulator of the GABAA receptor, and changes in the subunit composition of the
      GABAA receptor to the alpha4 subtype which is insensitive to benzodiazepine and
      GABA. Bioidentical progesterone supplement is no better than placebo in the
      treatment of women with focal onset epilepsy overall but shows superior efficacy
      in women whose seizures show robust perimenstrual exacerbation. CONCLUSION: There
      is sound evidence for the existence of catamenial epilepsy and class 3 evidence
      for adjunctive progesterone treatment of the perimenstrually exacerbated subtype.

PMID- 25770029
TI  - Differential impact of antiepileptic drugs on the effects of contraceptive
      methods on seizures: Interim findings of the epilepsy birth control registry.
AB  - PURPOSE: To present the interim findings of the Epilepsy Birth Control Registry
      (EBCR) regarding the impact of various contraceptive methods on seizures,
      stratified by antiepileptic drug (AED) type. METHODS: This is an observational
      study that reports interim findings on the first 750 subjects. RESULTS: There are
      significantly greater relative risks (RR) for both seizure increase and decrease
      with hormonal contraception (HC) than with non-hormonal contraception (NHC). The
      rates of HC experiences associated with seizure increase (21.0%) are greater than
      with NHC (3.9%) (RR=5.39 [95% CI=3.77-7.73, p<0.0001]). The rates of HC
      experiences associated with seizure decrease (10.3%) are greater than with NHC
      (5.6%) (RR=1.85 [95% CI=1.30-2.62, p=0.0006]). While differences can reflect
      biological effects or reporting bias, the finding of a greater RR for seizure
      increase with hormonal patch than with combined oral contraceptive, perhaps
      related to the delivery of substantially higher concentrations of hormones, and a
      greater RR for seizure decrease with depomedroxyprogesterone, known to reduce
      seizure frequency when used in dosages which produce amenorrhea, support
      biological effects. All AED categories showed significantly higher frequencies of
      reports of seizure increase when combined with HC than with NHC. RR for seizure
      increase with HC was higher with valproate than with any other AED category.
      There were no significant differences among AEDs for seizure decrease with HC at
      this juncture of the study. Overall, NEIAEDs had the most favorable profile with
      regard to reports of seizure increase and decrease when used with HC.
      CONCLUSIONS: Interim EBCR findings suggest that contraception category and
      interactions between contraception category and AED category are predictive
      factors for changes in seizure frequency in WWE.

PMID- 25770030
TI  - Quantitative targeted absolute proteomics for 28 human transporters in plasma
      membrane of Caco-2 cell monolayer cultured for 2, 3, and 4 weeks.
AB  - The purpose of the present study was to evaluate and compare the absolute protein
      expression levels of 28 drug-related transporters in Caco-2 cell monolayers
      cultured for 2, 3, and 4 weeks. Plasma membrane fractions of Caco-2 cells
      cultured on Transwell inserts for 2, 3 and 4 weeks were prepared and digested
      with trypsin, and then simultaneous absolute quantification of 28 transporters
      and Na(+)/K(+)-ATPase was conducted using our established quantitative targeted
      absolute proteomic technique. Nine transporters and Na(+)/K(+)-ATPase were
      detected. MDR1, BCRP, PEPT1, OSTalpha and OSTbeta were highly expressed (greater
      than 1 fmol/MUg protein), while MRP2, MRP4, OATP2B1 and MCT1 were moderately
      expressed (0.328-0.871 fmol/MUg protein). No significant difference was observed
      in the protein expression levels of these transporters or Na(+)/K(+)-ATPase among
      the 2-, 3- and 4-week cultures. The other 19 transporters, including MRP1, MRP3,
      OATP1A2, OATP3A1, OATP4A1, and OATP1B3, were not detected. This information about
      the rank order of transporter protein expression will be useful to predict what
      transporter(s) are likely or unlikely to influence the permeability of various
      compounds across monolayers of Caco-2 cells, which are widely used in drug
      development studies.

PMID- 25770031
TI  - A Brief Patient Self-administered Substance Use Screening Tool for Primary Care:
      Two-site Validation Study of the Substance Use Brief Screen (SUBS).
AB  - BACKGROUND: Substance use screening is widely encouraged in health care settings,
      but the lack of a screening approach that fits easily into clinical workflows has
      restricted its broad implementation. The Substance Use Brief Screen (SUBS) was
      developed as a brief, self-administered instrument to identify unhealthy use of
      tobacco, alcohol, illicit drugs, and prescription drugs. We evaluated the
      validity and test-retest reliability of the SUBS in adult primary care patients.
      METHODS: Adults aged 18-65 years were enrolled from urban safety net primary care
      clinics to self-administer the SUBS using touch-screen tablet computers for a
      test-retest reliability study (n = 54) and a 2-site validation study (n = 586).
      In the test-retest reliability study, the SUBS was administered twice within a 2
      week period. In the validation study, the SUBS was compared with reference
      standard measures, including self-reported measures and oral fluid drug tests. We
      measured test-retest reliability and diagnostic accuracy of the SUBS for
      detection of unhealthy use and substance use disorder for tobacco, alcohol, and
      drugs (illicit and prescription drug misuse). RESULTS: Test-retest reliability
      was good or excellent for each substance class. For detection of unhealthy use,
      the SUBS had sensitivity and specificity of 97.8% (95% confidence interval [CI],
      93.7-99.5) and 95.7% (95% CI, 92.4-97.8), respectively, for tobacco; and 85.2%
      (95% CI, 79.3-89.9) and 77.0% (95% CI, 72.6-81.1) for alcohol. For unhealthy use
      of illicit or prescription drugs, sensitivity was 82.5% (95% CI, 75.7-88.0) and
      specificity 91.1% (95% CI, 87.9-93.6). With respect to identifying a substance
      use disorder, the SUBS had sensitivity and specificity of 100.0% (95% CI, 92.7
      100.0) and 72.1% (95% CI, 67.1-76.8) for tobacco; 93.5% (95% CI, 85.5-97.9) and
      64.6% (95% CI, 60.2-68.7) for alcohol; and 85.7% (95% CI, 77.2-92.0) and 82.0%
      (95% CI, 78.2-85.3) for drugs. Analyses of area under the receiver operating
      curve (AUC) indicated good discrimination (AUC 0.74-0.97) for all substance
      classes. Assistance in completing the SUBS was requested by 11% of participants.
      CONCLUSIONS: The SUBS was feasible for self-administration and generated valid
      results in a diverse primary care patient population. The 4-item SUBS can be
      recommended for primary care settings that are seeking to implement substance use
      screening.

PMID- 25770032
TI  - Apparent Treatment-resistant Hypertension Among Individuals with History of
      Stroke or Transient Ischemic Attack.
AB  - BACKGROUND: Blood pressure control is a paramount goal in secondary stroke
      prevention; however, high prevalence of uncontrolled blood pressure and use of
      multiple antihypertensive medication classes in stroke patients suggest this goal
      is not being met. We determined the prevalence and factors associated with
      apparent treatment-resistant hypertension in persons with/without stroke or
      transient ischemic attack. METHODS: Data came from the REasons for Geographic And
      Racial Differences in Stroke (REGARDS) study, a national, population-based cohort
      of 30,239 black and white adults aged >=45 years, enrolled 2003-2007, restricted
      to 11,719 participants with treated hypertension. Apparent treatment-resistant
      hypertension was defined as (1) uncontrolled blood pressure (systolic >=140 mm Hg
      or diastolic >=90 mm Hg) with >=3 antihypertensive medication classes, or (2) use
      of >=4 antihypertensive medication classes, regardless of blood pressure level.
      Poisson regression was used to calculate characteristics associated with apparent
      treatment-resistant hypertension. RESULTS: Among hypertensive participants,
      prevalence of apparent treatment-resistant hypertension was 24.9% (422 of 1694)
      and 17.0% (1708 of 10,025) in individuals with and without history of stroke or
      transient ischemic attack, respectively. After adjustment for cardiovascular risk
      factors, the prevalence ratio for apparent treatment-resistant hypertension for
      those with versus without stroke or transient ischemic attack was 1.14 (95%
      confidence interval, 1.03-1.27). Among hypertensive participants with stroke or
      transient attack, male sex, black race, larger waist circumference, longer
      duration of hypertension, and reduced kidney function were associated with
      apparent treatment-resistant hypertension. CONCLUSIONS: The high prevalence of
      apparent treatment-resistant hypertension among hypertensive persons with history
      of stroke or transient ischemic attack suggests the need for more individualized
      blood pressure monitoring and management.

PMID- 25770033
TI  - Etiology of Pericarditis in a Prospective Cohort of 1162 Cases.
AB  - BACKGROUND: Pericarditis is a common disorder that is present in various
      pathologies and may be the first manifestation of an underlying systemic disease.
      The aims of this study were to describe the different causes of infectious and
      noninfectious pericarditis and compare them with those in the literature.
      METHODS: Between May 2007 and September 2012, we prospectively evaluated a
      strategy using a systematic prescription of tests for the different etiological
      causes of pericarditis in patients with acute pericarditis who were hospitalized
      in the Cardiology and Cardiac Surgery Department or admitted to the Emergency
      Department (University Hospital of Marseille). A total of 1162 patients with
      suspected pericarditis were included. A standardized diagnosis procedure was
      performed for 800 patients, and 362 had pericardiocentesis. RESULTS: Acute
      pericarditis was diagnosed in 933 patients. No diagnosis was established in 516
      patients (55%), 197 patients suffered from postinjury syndromes, and 156 had
      previously known diseases that were associated with pericarditis. Our survey
      allowed us to relate the probable cause of pericarditis in 64 cases. An
      infectious etiological diagnosis was established in 53 cases. In our study,
      postinjury syndrome was the leading cause of pericarditis, a new diagnosis was
      made in 6.7% of cases, and 16% of the diagnoses were linked to a secondary,
      underlying disease. CONCLUSION: Using this strategy, we were able to reduce the
      number of idiopathic cases. In many cases, the etiologies were still identified.
      Long-term follow-up in the management of idiopathic pericarditis should remain of
      great interest for the future diagnosis of other disorders that remain hidden.

PMID- 25770034
TI  - Brush Up Your Shakespeare! Democratization of Medical Knowledge for the 21(st)
      Century.

PMID- 25770036
TI  - Is the Stethoscope Becoming an Outdated Diagnostic Tool?

PMID- 25770037
TI  - Pulp revascularization after repositioning of impacted incisor with a dilacerated
      root and a detached apex.
AB  - Severely impacted and dilacerated incisors are rarely considered for surgical
      exposure because they may not respond favorably to orthodontic extrusion. These
      incisors are often extracted, resulting in the need for tooth replacement;
      however, prosthetic solutions are limited in growing patients. Transalveolar
      autotransplantation of an impacted incisor may be the only method to preserve the
      natural tooth and maintain the shape of the alveolus. The severely impacted upper
      central incisor (#9) with a developing root was diagnosed in a 9-year-old girl.
      The unfavorable tooth position and dilaceration of its root made orthodontic
      extrusion of the impacted incisor impossible. Initial orthodontic space opening
      at the recipient site was performed before the surgery. Transalveolar
      transplantation of the impacted incisor to its normal position was performed to
      avoid tooth extraction. The incisor was later aligned using fixed orthodontic
      appliances. At the 5-year follow-up, the transplanted incisor presented features
      that were typical of a revascularized tooth (ie, obliteration of root canal but a
      positive response to vitality tests). Healthy periodontal tissues and continued
      root development were also noted. However, the root apex, which separated from
      the transplant at the time of the surgery, continued formation in its initial
      position. Transalveolar transplantation of an unfavorably impacted upper central
      incisor with a dilacerated root is a successful treatment, which stands the test
      of time. The early stage of root development allowed revascularization of the
      tooth despite dilaceration of the root and detachment of its apex.

PMID- 25770035
TI  - Angiotensin-converting Enzyme Inhibitor Angioedema Requiring Admission to an
      Intensive Care Unit.
AB  - OBJECTIVE: The purpose of this study was to review consecutive cases of
      angiotensin-converting enzyme (ACE) inhibitor angioedema admitted to an intensive
      care unit. METHODS: Fifty subjects with ACE-inhibitor angioedema admitted from
      1998-2011 were reviewed. RESULTS: All 50 subjects were men, 62.8 +/- 8.4 years of
      age, 76% African Americans. Fifteen (30%) required ventilatory support and 2 (4%)
      required tracheostomy. Over half (56%) had taken ACE inhibitors for over a year.
      Logistic regression identified dyspnea and tongue involvement with the need for
      ventilatory support (P < .01). Hypercapnia (PaCO2 = 45.2 +/- 6.7; P = 0.046) also
      identified patients needing ventilatory support. CONCLUSIONS: Ventilatory support
      was provided for about one-third of those with ACE inhibitor-associated
      angioedema. Angioedema can occur even after extended use. Dyspnea and tongue
      involvement identified patients requiring ventilatory support.

PMID- 25770038
TI  - Incidence of missed inferior alveolar nerve blocks in vital asymptomatic subjects
      and in patients with symptomatic irreversible pulpitis.
AB  - INTRODUCTION: The purpose of this retrospective study was to determine the
      incidence of missed inferior alveolar nerve (IAN) blocks by using a 1- or 2
      cartridge volume of 2% lidocaine with 1:100,000 epinephrine in vital asymptomatic
      teeth and in emergency patients with symptomatic irreversible pulpitis. METHODS:
      As part of 37 studies, 3169 subjects/patients were evaluated for missed IAN
      blocks. The study included 2450 asymptomatic subjects and 719 emergency patients
      presenting with symptomatic irreversible pulpitis. Each subject or patient
      received either a 1- or 2-cartridge volume of 2% lidocaine with 1:100,000
      epinephrine. A missed block was defined as no lip numbness at 15-20 minutes after
      the IAN block. The effect of anesthetic volume on the incidence of missed blocks
      was assessed by using mixed models logistic regression with individual studies as
      a random effect. RESULTS: The incidence of missed blocks for asymptomatic
      subjects was 6.3% for the 1-cartridge volume and 3.8% for the 2-cartridge volume.
      For patients presenting with irreversible pulpitis, the incidence of missed
      blocks was 7.7% for the 1-cartridge volume and 2.3% for the 2-cartridge volume.
      In both asymptomatic subjects and patients with irreversible pulpitis, the 2
      cartridge volume was significantly (P = .0395) better than the 1-cartridge
      volume. There were no significant effects for pulpal diagnosis (P = .7523) or the
      pulpal diagnosis and anesthetic volume interaction (P = .3973). CONCLUSIONS:
      Concerning missed IAN blocks, we concluded that administration of a 2-cartridge
      volume was significantly better (P = .0395) than a 1-cartridge volume in both
      asymptomatic subjects and emergency patients presenting with irreversible
      pulpitis.

PMID- 25770040
TI  - Diversity of Histologic Patterns and Expression of Cytoskeletal Proteins in
      Canine Skeletal Osteosarcoma.
AB  - Osteosarcoma (OS), the most common bone tumor, includes OS of the head (OSH) and
      appendicular OS (OSA). In dogs, it is classified into 6 histologic subtypes:
      osteoblastic, chondroblastic, fibroblastic, telangiectatic, giant cell, and
      poorly differentiated. This study investigated the significance of the histologic
      classification relevant to clinical outcome and the histologic and
      immunohistochemical relationships between pleomorphism and expression of
      cytoskeletal proteins in 60 cases each of OSH and OSA. Most neoplasms exhibited
      histologic diversity, and 64% of OS contained multiple subtypes. In addition to
      the above 6 subtypes, myxoid, round cell, and epithelioid subtypes were observed.
      Although the epithelioid subtypes were observed in only OSH, no significant
      difference in the frequency of other subtypes was observed. Also, no significant
      relevance was observed between the clinical outcome and histologic subtypes.
      Cytokeratin (CK) was expressed in both epithelioid and sarcomatoid tumor cells in
      various subtypes, and all CK-positive tumor cells also expressed vimentin.
      Vimentin and alpha-smooth muscle actin (SMA) were expressed in all subtypes. A
      few SMA-positive spindle-shaped tumor cells exhibited desmin expression. Glial
      fibrillary acidic protein-positive tumor cells were observed in many subtypes,
      and some of these cells showed neurofilament expression. Although OSH exhibited
      significantly stronger immunoreactivity for SMA than OSA, no significant
      difference in other cytoskeletal proteins was observed. Some tumor cells had
      cytoskeletal protein expression compatible with the corresponding histologic
      subtypes, such as CK in the epithelioid subtype and SMA in the fibroblastic
      subtype. Thus, canine skeletal OS is composed of pleomorphic and heterogenous
      tumor cells as is reflected in the diversity of histologic patterns and
      expression of cytoskeletal proteins. 

PMID- 25770039
TI  - Distinct neural correlates of emotional and cognitive empathy in older adults.
AB  - Empathy is thought to be a mechanism underlying prosocial behavior across the
      lifespan, yet little is known about how levels of empathy relate to individual
      differences in brain functioning among older adults. In this exploratory study,
      we examined the neural correlates of affective and cognitive empathy in older
      adults. Thirty older adults (M=79 years) underwent fMRI scanning and
      neuropsychological testing and completed a test of affective and cognitive
      empathy. Brain response during processing of cognitive and emotional stimuli was
      measured by fMRI in a priori and task-related regions and was correlated with
      levels of empathy. Older adults with higher levels of affective empathy showed
      more deactivation in the amygdala and insula during a working memory task,
      whereas those with higher cognitive empathy showed greater insula activation
      during a response inhibition task. Our preliminary findings suggest that brain
      systems linked to emotional and social processing respond differently among older
      adults with more or less affective and cognitive empathy. That these
      relationships can be seen both during affective and non-emotional tasks of "cold"
      cognitive abilities suggests that empathy may impact social behavior through both
      emotional and cognitive mechanisms. 

PMID- 25770041
TI  - Environmental factors as modulators of neurodegeneration: insights from gene
      environment interactions in Huntington's disease.
AB  - Unlike many other neurodegenerative diseases with established gene-environment
      interactions, Huntington's disease (HD) is viewed as a disorder governed by
      genetics. The cause of the disease is a highly penetrant tandem repeat expansion
      encoding an extended polyglutamine tract in the huntingtin protein. In the year
      2000, a pioneering study showed that the disease could be delayed in transgenic
      mice by enriched housing conditions. This review describes subsequent human and
      preclinical studies identifying environmental modulation of motor, cognitive,
      affective and other symptoms found in HD. Alongside the behavioral observations
      we also discuss potential mechanisms and the relevance to other neurodegenerative
      disorders, including Alzheimer's and Parkinson's disease. In mouse models of HD,
      increased sensorimotor and cognitive stimulation can delay or ameliorate various
      endophenotypes. Potential mechanisms include increased trophic support, synaptic
      plasticity, adult neurogenesis, and other forms of experience-dependent cellular
      plasticity. Subsequent clinical investigations support a role for lifetime
      activity levels in modulating the onset and progression of HD. Stress can
      accelerate memory and olfactory deficits and exacerbate cellular dysfunctions in
      HD mice. In the absence of effective treatments to slow the course of HD,
      environmental interventions offer feasible approaches to delay the disease,
      however further preclinical and human studies are needed in order to generate
      clinical recommendations. Environmental interventions could be combined with
      future pharmacological therapies and stimulate the identification of
      enviromimetics, drugs which mimic or enhance the beneficial effects of cognitive
      stimulation and physical activity. 

PMID- 25770042
TI  - Overview of proteomics studies in obstructive sleep apnea.
AB  - Obstructive sleep apnea (OSA) is an underdiagnosed common public health concern
      causing deleterious effects on metabolic and cardiovascular health. Although much
      has been learned regarding the pathophysiology and consequences of OSA in the
      past decades, the molecular mechanisms associated with such processes remain
      poorly defined. The advanced high-throughput proteomics-based technologies have
      become a fundamental approach for identifying novel disease mediators as
      potential diagnostic and therapeutic targets for many diseases, including OSA.
      Here, we briefly review OSA pathophysiology and the technological advances in
      proteomics and the first results of its application to address critical issues in
      the OSA field. 

PMID- 25770044
TI  - Parkinson's disease and narcolepsy-like symptoms.
AB  - OBJECTIVE: Various sleep-related problems, for example, insomnia and symptoms of
      rapid eye movement behavior disorder (RBD), are common in patients with
      Parkinson's disease (PD). We studied the prevalence of symptoms of narcolepsy
      (NARC), hallucinations, and RBD and their association with other symptoms.
      METHODS: Altogether, 1447 randomly selected patients with PD, aged 43-89 years,
      participated in a questionnaire study. A structured questionnaire with 207 items
      was based on the Basic Nordic Sleep Questionnaire. Questions on demographics, PD,
      RBD, and other issues were included. RESULTS: The response rate was 59.0%; of
      these patients, 73% had answered to all questions that were used in the analyses
      (N = 623). The occurrence of suspected narcolepsy (Ullanlinna Narcolepsy Scale >=
      14 and Epworth Sleepiness Scale >= 11) was observed in 9.3% of the subjects (PD
      with NARC), RBD (REM Sleep Behavior Disorder Screening Questionnaire >= 6) in
      39.2% of all patients with PD, and in 62.1% of those with PD and NARC. In
      patients with PD, hallucinations before going to bed in the evening occurred in
      5.8%, hypnagogic hallucinations in 4.0%, hallucinations during night 8.3%, and
      hypnopompic hallucinations in 3.2%. Cataplexy symptoms occurred in 43.1% of
      subjects with PD and NARC. In a logistic regression analysis, PD with NARC was
      associated with RBD, all types of hallucinations, daytime sleepiness, fatigue,
      insomnia, and intense dreaming also when adjusted for age, sex, disease duration,
      and levodopa. CONCLUSIONS: Narcolepsy-like symptoms may be present in patients
      with PD. Symptoms of RBD were associated with symptoms of narcolepsy including
      symptoms of cataplexy.

PMID- 25770045
TI  - Highlights of PBTI Coimbra Conference on PRT of Plasma & Current Opinions on
      Pathogen Reduction Treatment of Blood Components.
AB  - Two experts from Octapharma and from Cerus addressed, in very concise ways, the
      concerns about non-viral inactivated FFP and how they managed to obtain highest
      standard of safety margin for pathogen reduction treatment [PRT] of plasma. The
      session was moderated by Portuguese Institute of Blood and Transplantation (PIBT)
      consultant advisor [Jerard Seghatchian] with long standing familiarity and
      international recognition in PR technologies for plasma, platelets and WB/red
      cells. The focus of conference was mainly on the criteria of acceptability of PRT
      FFP; added values of having diversity in choice without fears of liability, as
      both of PRT technologies provide an excellent safeguard margins, for more than a
      decade of usage. In most European countries, it is believed that patients' safety
      come first followed by the safe usage initiatives, in particular using locally
      available products. Portugal is finally going forward with the implementation PRT
      plasma using its own FFP for their clinical use. The round table Q&A session
      focused on the impacts of the additional processing, which is still continuously
      improving, on the residual/emerging pathogen infectivity; eliminating the
      clinical impacts of donors viable leukocytes; the degree of altered product
      potency in particular cold activation of FVII; and loss of endothelial
      permeability factors during fluid storage of plasma. Both speakers highlighted
      their product safety and clinical efficacy using both routine in vitro, including
      the modern proteomic tests to establish the relevant changes in various
      parameters and in the overall clinical outcomes. The advancements in
      pharmacovigilance and hemovigilance, regulatory aspects and cost effectiveness
      were also highlighted. A local speaker [from the PIBT] described the state of the
      art of local processing issues and overall required standards used both during
      validation and the intercept process scale up, which is going ahead smoothly to
      providing the highest safety standards PRT-intercept plasma locally, in
      production now. Overall this was an excellent conference, open to transfusion
      medicine specialists and other health care professionals, for feedback and
      quality awareness, of providing diversity in choice, to local clinicians, who
      demand the best for the ultimate patient requirements. This is achieved in a
      period where both cost effectiveness and affordability matter, so is the clinical
      outcome, which ultimately counts. There was an atmosphere of non-competitive
      collaboration and sharing knowledge and working togetherness, even between two
      manufacturer representatives, which made the conference most joyful event. This
      was the opportunity to the scientific update and sharing "the once upon a time"
      impossible task of going for PRT-plasmas in Portugal, making it a reality in
      their local setting, in real time using Portuguese plasmas. This is in fact the
      timely news in the period of austerity, to provide a pre launching session for
      reporting the state of the arts of Portugal achievements to staff, academician,
      laboratory experts and clinician alike.

PMID- 25770043
TI  - Discrimination and sleep: a systematic review.
AB  - An increasing body of literature indicates that discrimination has a negative
      impact on health; poor sleep may be an underlying mechanism. The primary
      objective of this review was to examine existing studies on the relationship
      between discrimination and sleep to clarify (a) the potential role of
      discrimination in shaping population patterns of sleep and sleep disparities, and
      (b) the research needed to develop interventions at individual and institutional
      levels. We identified articles from English-language publications in PubMed and
      EBSCO databases from inception through July 2014. We employed a broad definition
      of discrimination to include any form of unfair treatment and all self-reported
      and objectively assessed sleep outcomes, including duration, difficulties, and
      sleep architecture. Seventeen studies were identified: four prospective, 12 cross
      sectional, and one that utilized a daily-diary design. Fifteen of the 17 studies
      evaluated interpersonal discrimination as the exposure and the majority of
      studies included self-reported sleep as the outcome. Only four studies
      incorporated objective sleep assessments. All 17 studies identified at least one
      association between discrimination and a measure of poorer sleep, although
      studies with more detailed consideration of either discrimination or sleep
      architecture revealed some inconsistencies. Taken together, existing studies
      demonstrate consistent evidence that discrimination is associated with poorer
      sleep outcomes. This evidence base can be strengthened with additional
      prospective studies that incorporate objectively measured aspects of sleep. We
      outline important extensions for this field of inquiry that can inform the
      development of interventions to improve sleep outcomes, and consequently promote
      well-being and reduce health inequities across the life course.

PMID- 25770046
TI  - Purification and stability of octameric mitochondrial creatine kinase isoform
      from herring (Clupea harengus) organ of vision.
AB  - Creatine kinases (CKs) constitute a large family of isoenzymes that are involved
      in intracellular energy homeostasis. In cells with high and fluctuating energy
      requirements ATP level is maintained via phosphocreatine hydrolysis catalyzed by
      creatine kinase. In contrast to invertebrates and higher vertebrates, in
      poikilothermic vertebrates the adaptations for the regulation of energy
      metabolism by changes in the oligomeric state of CK isoforms are not well known.
      The present study aimed at identification of herring eye CK isoforms and focuses
      on factors affecting the CK-octamer stability. In addition to the CK octamer,
      three different dimeric isoforms of CK were detected by cellulose acetate native
      electrophoresis. Destabilization of octamer was studied in the presence of TSAC
      substrates and about 50% of octamers dissociated into dimers within 24h.
      Moreover, we found that the increase of temperature from 4  degrees C to 30 
      degrees C caused rapid inactivation of dimers in TSAC-treated samples but did not
      affect octameric structures. In a thermostability assay we demonstrated that
      octamers retain their activity even at 50  degrees C. Our results indicate that
      destabilization of the octameric structure can lead to loss of enzyme activity at
      higher temperatures (above 30  degrees C). Furthermore, our results based on N
      terminal sequence analysis suggest that probably the mitochondrial s-type CK,
      rather than u-type, is predominantly expressed in herring eye. In conclusion the
      existence of four various CK isoforms in one organ may reflect complex regulation
      of energy metabolism in the phototransduction process in teleost fishes.

PMID- 25770047
TI  - Comparative analyses of the cholinergic locus of ChAT and VAChT and its
      expression in the silkworm Bombyx mori.
AB  - The cholinergic locus, which encodes choline acetyltransferase (ChAT) and
      vesicular acetylcholine transporter (VAChT), is specifically expressed in
      cholinergic neurons, maintaining the cholinergic phenotype. The organization of
      the locus is conserved in Bilateria. Here we examined the structure of
      cholinergic locus and cDNA coding for ChAT and VAChT in the silkworm, Bombyx
      mori. The B. mori ChAT (BmChAT) cDNA encodes a deduced polypeptide including a
      putative choline/carnitine O-acyltransferase domain and a conserved His residue
      required for catalysis. The B. mori VAChT (BmVAChT) cDNA encodes a polypeptide
      including a putative major facilitator superfamily domain and 10 putative
      transmembrane domains. BmChAT and BmVAChT cDNAs share the 5'-region corresponding
      to the first and second exon of cholinergic locus. Polymerase chain reaction
      analyses revealed that BmChAT and BmVAChT mRNAs were specifically expressed in
      the brain and segmental ganglia. The expression of BmChAT was detected 3 days
      after oviposition. The expression level was almost constant during the larval
      stage, decreased in the early pupal stage, and increased toward eclosion. The
      average ratios of BmChAT mRNA to BmVAChT mRNA in brain-subesophageal ganglion
      complexes were 0.54+/-0.10 in the larvae and 1.92+/-0.11 in adults. In addition,
      we examined promoter activity of the cholinergic locus and localization of
      cholinergic neurons, using a baculovirus-mediated gene transfer system. The
      promoter sequence, located 2kb upstream from the start of transcription, was
      essential for cholinergic neuron-specific gene oexpression. Cholinergic neurons
      were found in several regions of the brain and segmental ganglia in the larvae
      and pharate adults.

PMID- 25770048
TI  - Improving patient recall of information: Harnessing the power of structure.
AB  - OBJECTIVE: Assess the amount of medical information laypeople recall, investigate
      the impact of structured presentation on recall. METHODS: 105 first-year
      psychology students (mean age 21.5+/-3.8 years; 85% female) were randomised to
      two information-presentation conditions: structured (S group) and nonstructured
      (NS group). Students watched a video of a physician discharging a patient from
      the emergency department. In the S Group, content (28 items of information) was
      divided into explicit "chapters" with "chapter headings" preceding new
      information. Afterwards, participants wrote down all information they recalled on
      an empty sheet of paper. RESULTS: The S group (N=57) recalled significantly more
      items than NS group (N=41) (8.12+/-4.31 vs. 5.71+/-3.73; p=0.005), rated
      information as easier to understand (8.0+/-1.9 vs. 6.1+/-2.2; p<0.001) and better
      structured (8.5+/-1.5 vs. 5.5+/-2.7; p<0.001); they rather recommended the
      physician to friends (7.1+/-2.7 vs. 5.8+/-2.6; p<0.01). CONCLUSION: University
      students recalled around 7/28 items of information presented. Explicit structure
      improved recall. PRACTICE IMPLICATIONS: Practitioners must reduce the amount of
      information conveyed and structure information to improve recall.

PMID- 25770049
TI  - Time intervals in diagnosing Parkinson's disease: The patients' views.
AB  - OBJECTIVE: To explore patients' views on their pathway to the diagnosis of
      Parkinson's disease (PD). METHODS: A qualitative study of 52 essays written by
      patients with PD, using comparative content analysis. RESULTS: Patients divide
      their diagnostic pathway into three time intervals: recognition of the symptoms;
      the decision to seek help; and the process of diagnosing PD. Patients have
      difficulties recognizing the prodromal symptoms of PD (their knowledge is based
      on public figures with advanced PD) and mention their general practitioners do as
      well. The decision to seek help is influenced by the patient's attitude toward
      health care and by their significant others. More than half of the patients
      believe their diagnosis was delayed. However, the majority of all patients are
      satisfied with their diagnostic trajectory. CONCLUSION: The pathway to diagnosing
      PD is an iterative process influenced by patient-, health care provider- and
      disease-related factors. Despite possible delay in diagnosis, patients are
      content with their pathway. PRACTICE IMPLICATIONS: In order to facilitate earlier
      diagnosis and timely therapeutic intervention (in particular with regard to
      future possibilities for disease modifying therapy), effort is required to
      increase the recognition of prodromal symptoms of PD by patients, their
      significant others and health care providers.

PMID- 25770050
TI  - Treatment decision making experiences of migrant cancer patients and their
      families in Australia.
AB  - OBJECTIVE: To explore treatment decision-making experiences of Australian
      migrants with cancer from Arabic, Chinese, or Greek backgrounds and their
      relatives. METHODS: 73 patients and 18 caregivers from cancer support groups and
      oncology clinics participated in either a focus group (n=14) or semi-structured
      interview (n=21) conducted in the participant's own language. Participant
      treatment decision-making preferences were discussed as part of patients' overall
      treatment experience and a thematic analysis conducted. RESULTS: Four main themes
      emerged from the data: (1) perceived role of the patient in decision-making; (2)
      access to information and the impact of language; (3) cultural influences (4)
      family involvement. The majority of participants experienced passive involvement
      during treatment consultations, but expressed a desire for greater involvement.
      Language rather than culture was a greater obstacle to active participation.
      Difficulty communicating effectively in English was the most significant barrier
      to participation in treatment decisions. To overcome language challenges,
      participants actively sought information from alternative sources. CONCLUSION:
      This study provides new insights into the influence of language and culture on
      the treatment decision-making experiences of migrants with cancer and their
      families within the Australian cancer care system. PRACTICE IMPLICATIONS: To
      reduce health disparities doctors need to address language difficulties and be
      aware of cultural differences.

PMID- 25770051
TI  - Cloning and expression analysis of CaPIP1-1 gene in pepper (Capsicum annuum L.).
AB  - Plant aquaporins are responsible for water transmembrane transport, which play an
      important role on abiotic and biotic stresses. A novel plasma membrane intrinsic
      protein of CaPIP1-1 was isolated from the pepper P70 according to transcriptome
      databases of Phytophthora capsici inoculation and chilling stress library. CaPIP1
      1, which is 1155 bp in length with an open reading frame of 861 bp, encoded 286
      amino acids. Three introns, exhibited CT/AC splice junctions, were observed in
      CaPIP1-1. The numbers and location of introns in CaPIP1-1 were the same as
      observed in tomato and potato. CaPIP1-1 was abundantly expressed in pepper fruit.
      Increased transcription levels of CaPIP1-1 were found in the different stresses,
      including chilling stress, salt stress, mannitol stress, salicylic acid, ABA
      treatment and Phytophthora capsici infection. The expression of CaPIP1-1 was
      downregulated by 50 MUM HgCl2 and 100 MUM fluridone. The pepper plants silenced
      CaPIP1-1 in cv. Qiemen showed growth inhibition and decreased tolerance to salt
      and mannitol stresses using detached leaf method.

PMID- 25770052
TI  - Lack of genetic associations between PPAR-gamma gene rs1801282 polymorphism and
      Alzheimer's disease in general population: a meta-analysis.
AB  - Published studies have evaluated the association between PPAR-gamma rs1801282
      polymorphism and Alzheimer's disease (AD) susceptibility. However, a definitive
      conclusion remains elusive. The aim of this study was to derive a more precise
      estimation of this association. We searched PubMed, Embase, Alzgene database,
      Chinese National Knowledge Infrastructure (CNKI), China Biological Medicine
      Database and Wanfang Databases for related studies. Twelve case-control studies
      with a total of 4874 cases and 5439 controls were finally identified to be
      eligible studies in this meta-analysis. The association was assessed by
      summarizing the odds ratios (ORs) with the corresponding 95% confidence intervals
      (CIs). Overall, there was no significant association between PPAR-gamma rs1801282
      polymorphism and Alzheimer's disease risk in all genetic models (the allele model
      G vs. C: OR=1.09, 95% CI 0.99-1.19, p=0.07; the homozygous model GG vs. CC:
      OR=1.04, 95% CI 0.75-1.44, p=0.80; heterozygote model GC vs. CC: OR=1.11, 95% CI
      1,00-1.22, p=0.05; the dominant model GG+GC vs. CC: OR=1.10, 95% CI 1.00-1.22,
      p=0.05; the recessive model GG vs. GC+CC: OR=1.02, 95% CI 0.74-1.41, p=0.90). In
      subgroup analysis by ethnicity, no significant difference was found in both
      Asians and Caucasians. In summary, the present meta-analysis suggests that the
      PPAR-gamma rs1801282 polymorphism may not be associated with genetic
      susceptibility of AD in general population. 

PMID- 25770053
TI  - Modeling multiple infection of cells by viruses: Challenges and insights.
AB  - The multiple infection of cells with several copies of a given virus has been
      demonstrated in experimental systems, and has been subject to previous
      mathematical modeling approaches. Such models, especially those based on ordinary
      differential equations, can be characterized by difficulties and pitfalls. One
      such difficulty arises from what we refer to as multiple infection cascades. That
      is, such models subdivide the infected cell population into sub-populations that
      are carry i viruses, and each sub-population can in principle always be further
      infected to contain i + 1 viruses. In order to study the model with numerical
      simulations, the infection cascade needs to be cut artificially, and this can
      influence the results. This is shown here in the context of the simplest setting
      that involves a single, homogeneous virus population. If the viral replication
      rate is sufficiently fast, then most infected cells will accumulate in the last
      member of the infection cascade, leading to incorrect numerical results. This can
      be observed even with relatively long infection cascades, and in this case
      computational costs associated with a sufficiently long infection cascade can
      render this approach impractical. We subsequently examine a more complex scenario
      where two virus types/strains with different fitness are allowed to compete.
      Again, we find that the length of the infection cascade can have a crucial
      influence on the results. Competitive exclusion can be observed for shorter
      infection cascades, while coexistence can be observed for longer infection
      cascades. More subtly, the length of the infection cascade can influence the
      equilibrium level of the populations in numerical simulations. Studying the model
      in a parameter regime where an increase in the infection cascade length does not
      influence the results, we examine the effect of multiple infection on the outcome
      of competition. We find that multiple infection can promote coexistence of virus
      types if there is a degree of intracellular niche separation. If this is not the
      case, the only outcome is competitive exclusion, similar to equivalent models
      that do not take into account multiple infection of cells. We further find that
      multiple infection has a reduced ability to allow coexistence if virus spread is
      spatially restricted compared to a well-mixed system. These results provide
      important insights when analyzing and interpreting multiple infection models. 

PMID- 25770054
TI  - Treatment of herpes simplex labialis in macule and vesicle phases with
      photodynamic therapy. Report of two cases.

PMID- 25770055
TI  - Demarcation laser photocoagulation induced retinal necrosis and rupture resulting
      in large retinal tear formation.
AB  - Retinal tears after laser photocoagulation are a rare complication that occurs
      after intense laser. It is talked about among retina specialist occurring
      particularly at the end of a surgical case while applying endophotocoagulation;
      to the best our knowledge, there are no reports in the literature of a large
      retinal tear induced after attempted in-office demarcation laser photocoagulation
      (DLP) that simulated a giant retinal tear. DLP has been employed in the
      management of selected cases of macula sparring rhegmatogenous retinal detachment
      (RRD). Even though extension of the retinal detachment through the "laser
      barrier" is considered a failure of treatment, few complications have been
      described with the use of this less invasive retinal detachment repair technique.
      We describe a case of a high myopic woman who initially was treated with
      demarcation laser photocoagulation for an asymptomatic retinal detachment
      associated with a single horseshoe tear and a full thickness large retinal tear
      was created where the laser was placed. Intense laser photocoagulation resulted
      in abrupt laser induced retinal necrosis and rupture creating this large retinal
      break. Proper laser technique should reduce the risks associated with this
      procedure. 

PMID- 25770056
TI  - Differences in paired-pulse inhibition and facilitation in the dentate gyrus and
      CA3 field between dorsal and ventral rat hippocampus.
AB  - We studied the processes of inhibition and facilitation in the dentate gyrus (DG)
      and the CA3 field by examining the effects of paired-pulse stimulation on the
      evoked population spike (PS) in dorsal (DH) and ventral (VH) hippocampal slices
      from the adult rat. The antidromic-orthodromic (A-O) and the orthodromic
      orthodromic (O-O) paired-pulse stimulation protocols were used at varying inter
      pulse intervals (IPI). In the DG, the A-O stimulation produced an early
      depression of PS lasting 30-40ms which was significantly stronger in the VH
      compared with DH. The O-O stimulation produced a biphasic pattern of effects, in
      both dorsal and ventral DG, consisting of an early depression of PS followed by
      facilitation at relatively longer intervals. In the DH but not the VH the phase
      of facilitation was followed by a late depression of PS (>200ms). In the CA3
      field both A-O and O-O stimulation had a biphasic effect consisting of an early
      phase of strong depression of similar strength in DH and VH. The depression was
      followed by a phase of facilitation which was more pronounced with O-O
      stimulation. The facilitation observed with the O-O stimulation was much stronger
      in DH than VH and in DH only it was significantly reduced by the antagonist of
      GABAB receptors CGP52432. Furthermore, the facilitation was insensitive to
      changes in [Ca(2+)]o in both hippocampal poles. These findings suggest that the
      dorsal compared with ventral DG is more amenable to fast-frequency input but
      filters out slow-frequency inputs more reliably while the gating and
      amplification of the excitatory input in the CA3 circuitry is more prominent in
      DH than in VH. 

PMID- 25770057
TI  - Aquaporins and blood-brain barrier permeability in early edema development after
      traumatic brain injury.
AB  - Traumatic brain injury (TBI) is a major contributor to mortality and morbidity.
      The pathophysiology involves development of brain edema. Therapeutic options are
      limited as the mechanisms are not fully understood. Changes in the function of
      the blood-brain barrier (BBB), as well as variations in aquaporin expression,
      have been proposed to be involved in the development of the edema but the
      contribution of each factor has not been fully elucidated. In order to evaluate
      these mechanisms, in a potential window of opportunity, the early dynamic
      response was studied using an animal model causing a moderate TBI. Sprague-Dawley
      rats were subjected to blunt controlled head trauma and followed for up to four
      days by magnetic-resonance-imaging, immunohistofluorescence,
      immunohistochemistry, and quantitative protein analysis. Non-traumatized animals
      served as controls. TBI resulted in a midline shift and a decrease in Apparent
      Diffusion Coefficient, indicating a hemispheric enlargement due to cytotoxic
      edema. The tight junction protein Zona Occludens-1 was decreased (-25%) and
      associated with an increased IgG permeability (+20%) in the perilesional brain
      tissue in accordance with a BBB breakdown. The total amount of AQP4 protein
      decreased (-20%). The disruption of the BBB lasted for 4 days while the impact on
      AQP4 levels disappeared between day 1 and 4. Our findings shows that blunt focal
      brain injury results in an early development of brain edema involving both
      cytotoxic and vasogenic components, a persistent BBB breakdown and a temporary
      decrease in AQP4, and indicates that both types of edemas and mechanisms should
      be targeted in TBI treatment. 

PMID- 25770058
TI  - Prevention of status epilepticus-induced brain edema and neuronal cell loss by
      repeated treatment with high-dose levetiracetam.
AB  - The management of status epilepticus (SE) is important to prevent mortality and
      the development of post-SE symptomatic epilepsy. Acquired epilepsy after an
      initial brain insult by SE can be experimentally reproduced in the murine model
      of SE induced by pilocarpine. In the present study, we evaluated the possibility
      of treatment with a high-dose of levetiracetam in this model. Repeated treatment
      with high-dose levetiracetam after termination of SE by diazepam significantly
      prevented the incidence of spontaneous recurrent seizures and mortality for at
      least 28 days. To determine the brain alterations after SE, magnetic resonance
      imaging was performed. Both T2-weighted imaging and diffusion-weighted imaging
      showed changes in the limbic regions. These changes in the limbic regions
      demonstrated the development of cytotoxic edema three hours after SE, followed by
      the development of vasogenic edema two days after SE. In the pilocarpine-SE
      model, the incidence of spontaneous recurrent seizures after SE was strongly
      associated with neuronal damage within a few hours to days after SE by the
      development of vasogenic edema via the breakdown of the blood-brain barrier in
      the limbic regions. High-dose levetiracetam significantly suppressed the
      parameters in the limbic areas. These data indicate that repeated treatment with
      high-dose levetiracetam for at least two days after SE termination by diazepam is
      important for controlling the neuronal damage by preventing brain edema.
      Therefore, these findings suggest that early treatment with high-dose
      levetiracetam after SE termination by diazepam may protect against adverse
      sequelae via the inhibition of neurotoxicity induced by brain edema events. 

PMID- 25770059
TI  - Statin Use Is Associated With Improved Prognosis of Colorectal Cancer in Taiwan.
AB  - BACKGROUND: Statins are widely used for hyperlipidemia control and might also
      exhibit anticancer properties. This study explored whether statin use is
      associated with the prognosis of curatively resected colorectal cancer (CRC).
      MATERIALS AND METHODS: Using data from the Taiwan Cancer Registry, we established
      a population-based cohort of patients who received curative surgery for stage I,
      II, or III CRC. Data related to prescription medications and comorbidities were
      retrieved from the database of the National Health Insurance program of Taiwan.
      Statin users were defined as patients who had used statins within 1 year before
      their cancer diagnosis. Univariate and multivariate analyses were used to compare
      cancer-specific survival (CSS) and overall survival (OS) between statin users and
      patients who had never used statins (never users). In the multivariate analysis,
      we used propensity scores to adjust for age, sex, diagnosis year, physician
      visits, hospitalization, conjunctive medications, and comorbidities. RESULTS: A
      total of 17,115 patients were enrolled; 2145 (13%) of these patients were statin
      users, and 14,970 (87%) were never users. After adjusting for other potential
      prognostic factors, statin use was an independent predictor for longer CSS
      (hazard ratio [HR], 0.77; 95% confidence interval [CI], 0.68-0.88; P < .001) and
      OS (HR, 0.82; 95% CI, 0.74-0.92; P < .001). These associations were consistent
      across subgroups, including sexes, tumor stages, and age cohorts, and in CRC
      patients who suffered from diabetes and hypertension. CONCLUSION: Statin use is
      associated with an improved prognosis of curatively resected CRC.

PMID- 25770060
TI  - Laminin beta3 expression as a prognostic factor and a predictive marker of
      chemoresistance in colorectal cancer.
AB  - OBJECTIVE: Laminin-332, a marker of epithelial-mesenchymal transition, is
      composed of a heterotrimer of alpha3, beta3 and gamma2 chains that regulates cell
      adhesion and migration. This study aimed to disclose the respective clinical
      significance of laminin beta3 immunoexpression in colorectal cancer as a
      prognostic factor and a predictive marker of chemoresistance. METHODS: Tissue
      specimens from 323 Stage II and 232 Stage III colorectal cancer patients who
      underwent curative resection were assessed using laminin beta3 immunostaining.
      RESULTS: Among Stage III colorectal cancer patients, comparisons of 5-year
      disease-free survival rates revealed a poorer prognosis for the laminin beta3
      high group than for the laminin beta3-low group (52.3 vs. 70.7%, P = 0.038),
      while there was no significant difference among Stage II patients. Among laminin
      beta3-low Stage III patients, those who received adjuvant chemotherapy showed
      marginally better disease-free survival than those who did not receive it (75.8
      vs. 62.8%; P = 0.096). Furthermore, multivariate analysis corroborated a distinct
      benefit of adjuvant chemotherapy in laminin beta3-low patients (P = 0.035; hazard
      risk ratio = 1.66). Analyses of the laminin beta3-high group, however, failed to
      show significance. CONCLUSIONS: Laminin beta3 chain immunoreactivity was a poor
      prognostic factor for Stage III colorectal cancer patients, and laminin beta3
      high patients of Stage III colorectal cancer derived no survival benefit from
      adjuvant chemotherapy.

PMID- 25770061
TI  - Characteristics and prognosis of acute myocardial infarction by discharge
      diagnosis: the Reasons for Geographic and Racial Differences in Stroke study.
AB  - PURPOSE: To compare the characteristics and prognosis of acute myocardial
      infarctions (AMIs) that were not the primary reason for hospitalization, and thus
      not primary discharge diagnosis, to AMIs that were the primary reason for
      hospitalization. METHODS: Primary discharge diagnoses for Reasons for Geographic
      and Racial Differences in Stroke study participants (black and white men and
      women age >=45 years) with adjudicated AMIs were categorized as "AMI" or "other".
      Cox models were used to compare mortality up to 5 years post-AMI between primary
      discharge diagnoses of AMI and other. RESULTS: Of 871 AMIs, primary discharge
      diagnosis was not AMI in 550 (63%). When primary discharge diagnosis was not AMI,
      average troponin elevations were smaller and heart failure was more common.
      Adjusted for participant and hospitalization characteristics, all-cause, coronary
      heart disease, and cardiovascular disease mortality after AMI were similar
      between groups (hazard ratios [95% confidence intervals]: 1.08 [0.80-1.47]; 1.29
      [0.76-2.18]; and 0.86 [0.58-1.27], respectively). CONCLUSIONS: Studies limited to
      individuals with primary discharge diagnosis of AMI may underestimate the burden
      of AMI and exclude a group with elevated risk of all-cause, coronary heart
      disease, and cardiovascular disease mortality.

PMID- 25770062
TI  - Structural origin of the drastic modification of second harmonic generation
      intensity pattern occurring in tail muscles of climax stages xenopus tadpoles.
AB  - Second harmonic generation (SHG) microscopy is a powerful tool for studying
      submicron architecture of muscles tissues. Using this technique, we show that the
      canonical single frequency sarcomeric SHG intensity pattern (SHG-IP) of
      premetamorphic xenopus tadpole tail muscles is converted to double frequency (2f)
      sarcomeric SHG-IP in metamorphic climax stages due to massive physiological
      muscle proteolysis. This conversion was found to rise from 7% in premetamorphic
      muscles to about 97% in fragmented muscular apoptotic bodies. Moreover a 66%
      conversion was also found in non-fragmented metamorphic tail muscles. Also, a
      strong correlation between predominant 2f sarcomeric SHG-IPs and myofibrillar
      misalignment is established with electron microscopy. Experimental and
      theoretical results demonstrate the higher sensitivity and the supra resolution
      power of SHG microscopy over TPEF to reveal 3D myofibrillar misalignment. From
      this study, we suggest that 2f sarcomeric SHG-IP could be used as signature of
      triad defect and disruption of excitation-contraction coupling. As the mechanism
      of muscle proteolysis is similar to that found in mdx mouse muscles, we further
      suggest that xenopus tadpole tail resorption at climax stages could be used as an
      alternative or complementary model of Duchene muscular dystrophy. 

PMID- 25770063
TI  - Comparison of the effect of multicomponent and resistance training programs on
      metabolic health parameters in the elderly.
AB  - Physical activity interventions such as resistance training (RT) and
      multicomponent (MCT) exercise training are known to improve functional mobility
      and reduce the risk of disability among the elderly. Less evidence exists
      regarding the effectiveness of such exercises to improve metabolic risk factors
      for age related conditions. This study aimed to compare the effects of MCT and RT
      programs on metabolic health parameters in healthy elderly. METHODS: Twenty one
      and 18 subjects completed a 12-week MCT and RT program respectively. Before and
      after intervention, body composition, functional ability, aerobic fitness and
      metabolic health parameters including lipid profile, inflammatory markers,
      glucose metabolism, hormones and growth markers were examined. Circulating
      concentrations of epidermal growth factor increased significantly in the MCT
      group from 35.8 +/- 29.4 to 56.1 +/- 35 pg/ml. High molecular weight adiponectin
      decreased significantly in the RT group from 4.7 +/- 2.9 to 4.2 +/- 2.3 MUg/ml
      (p=0.03). No other biochemical parameter was significantly altered within either
      group. A significant between group difference was found for both ferritin
      (p=0.02) and EGF (p=0.01), with concentrations of ferritin decreasing in the MCT
      group and increasing in the RT group and concentration of EGF increasing in the
      MCT group yet decreasing in the RT group. The MCT program improved results of
      functional tests including chair stand and habitual walking speed. Present
      findings suggest that although both the MCT and RT interventions were enough to
      produce functional and physical benefits, different training programs and/or
      exercise dose are required to improve metabolic health in healthy older adults.

PMID- 25770064
TI  - The effect of obstacle gait training on the plantar pressure and contact time of
      elderly women.
AB  - OBJECTIVE: The aim of the present study was to examine the effect of gait
      training using obstacle on the plantar pressure and contact time in elderly
      women. METHODS: A total of 24 elderly women who were residing in communities in D
      city, South Korea aged 79.9 +/- 2.2, 154.5 +/- 7.6 cm in height, and 56.2 +/- 5.2
      kg in weight participated in this study. The participants conducted obstacle gait
      training for 8 weeks and foot contact time and foot pressure right before and
      after crossing the obstacle were measured for 3 times: before the intervention,
      at the 4 weeks, and 8 weeks using F-scan (Tekscan, USA). RESULTS: The results
      show that foot contact time did not decrease right before crossing the obstacle
      but decreased right after crossing the obstacle (p<0.05). Foot pressure moved
      from the end of the frontal foot to the midfoot (MF) and heel (HL) right before
      crossing the obstacle (p<0.05). Foot pressure increased in lesser toe (LT) right
      after crossing the obstacle (p<0.05). CONCLUSION: These results indicate proper
      weight distribution in feet, increased foot stability due to increased muscle
      power and flexibility, and improved strategy to cope with the obstacle. The
      obstacle gait training may be helpful to the elderly who would either fear for or
      limit outdoor activities due to the risk of falls based on the result of this
      study.

PMID- 25770065
TI  - Update on laryngeal disorders and treatment.
AB  - Laryngeal disorders are relatively common in the horse, and thorough diagnostic
      evaluation is essential to make an accurate definitive diagnosis and selection of
      appropriate treatment. The value of exercising endoscopy must not be overlooked,
      and the recent development of dynamic (overground) endoscopy is providing new
      insights into dynamic laryngeal lesions. The focus of this article will be on
      recently described disorders and treatments or modifications to existing
      treatments. It summarizes the numerous investigations attempting to perfect the
      laryngoplasty procedure for treatment of laryngeal hemiplegia. The newly
      described conditions, bilateral dynamic laryngeal collapse, and dynamically
      flaccid epiglottis will also be discussed. 

PMID- 25770066
TI  - Update on disorders and treatment of the guttural pouch.
AB  - The most common disorders of the equine guttural pouches are empyema, tympany,
      mycosis, and temporohyoid osteoarthropathy. Diagnosis of these conditions is made
      primarily by imaging with endoscopy, radiographs, computed tomography, and/or
      MRI. Medical treatment with anti-inflammatories, antimicrobials, and/or
      antifungals may be successful in some cases, but many of these disorders
      necessitate surgical intervention. Direct surgical approaches to the guttural
      pouch are difficult because of their complex anatomy and relationship with
      important structures, thus precipitating a move toward minimally invasive
      procedures when possible. 

PMID- 25770067
TI  - Update on interstitial pneumonia.
AB  - Interstitial pneumonias encompass a wide variety of acute and chronic respiratory
      diseases and include the specific diseases equine multinodular pulmonary fibrosis
      and acute lung injury and acute respiratory distress. These diseases have been
      diagnosed in all age groups of horses, and numerous agents have been identified
      as potential causes of interstitial pneumonia. Despite the varied causes,
      interstitial pneumonia is uniformly recognized by the severity of respiratory
      disease and often poor clinical outcome. This article reviews the causal agents
      that have been associated with the development of interstitial pneumonia in
      horses. Pathophysiology, clinical diagnosis, and treatment options are discussed.

PMID- 25770068
TI  - Update on noninfectious inflammatory diseases of the lower airway.
AB  - Inflammatory airway disease and recurrent airway obstruction are 2 nonseptic
      diseases of the equine respiratory system with a shared cause of exposure to
      particulate matter. They appear to occupy 2 ends of a spectrum of disease, but
      are differentiated by history, clinical signs, and response to treatment.
      Diagnosis can be made by sampling of respiratory fluids and lung function
      testing. Treatment consists of environmental modification and pharmacologic
      treatment with systemic or inhaled corticosteroids and bronchodilators. 

PMID- 25770069
TI  - Update on exercise-induced pulmonary hemorrhage.
AB  - Exercise-induced pulmonary hemorrhage (EIPH) is an important disease of horses
      that perform high-intensity athletic activity. EIPH is an ongoing concern for the
      racing industry because of its high prevalence; potential impact on performance;
      welfare concerns; and use of prophylactic medications, such as furosemide, on
      race day. During the last 10 years, significant progress has been made in
      understanding the pathogenesis and risk factors for EIPH and the impact of the
      disease on performance and career. This article summarizes the most recent
      advances in EIPH.

PMID- 25770070
TI  - Thoracic trauma in horses.
AB  - Traumatic injuries involving the thorax can be superficial, necessitating only
      routine wound care, or they may extend to deeper tissue planes and disrupt
      structures immediately vital to respiratory and cardiac function. Diagnostic
      imaging, especially ultrasound, should be considered part of a comprehensive
      examination, both at admission and during follow-up. Horses generally respond
      well to diligent monitoring, intervention for complications, and appropriate
      medical or surgical care after sustaining traumatic wounds of the thorax. This
      article reviews the various types of thoracic injury and their management. 

PMID- 25770072
TI  - Updates on respiratory medicine and surgery.

PMID- 25770073
TI  - Statin adherence and LDL cholesterol levels. Should we assess adherence prior to
      statin upgrade?
AB  - BACKGROUND: Adherence to statin therapy has been shown to be suboptimal. In
      statin-treated patients with residual elevated low density lipoprotein
      cholesterol (LDL-C) levels the physician must decide whether to switch to a more
      potent statin or try and achieve better adherence. We examined the association
      between adherence and LDL-C within low, moderate and high intensity statin groups
      in a "real world" setting. METHODS: We assessed annual adherence by the mean MPR
      (Medication Possession Ratio = number of purchased/prescribed daily doses) in
      unselected patient group. Statins were stratified (ACC/AHA Guideline) into low,
      moderate and high intensity groups. The impact of adherence on LDL levels was
      assessed by LOESS (locally weighted scatter plot smoothing). RESULTS: Out of 1183
      patients 173 (14.6%) were treated with low, 923 (78.0%) with moderate and 87
      (7.4%) with high intensity statins. Statin intensity was inversely associated
      with adherence (MPR 77+/-21, 73+/-22 and 69+/-21% for low, moderate and high
      intensity respectively, p=0.018). Non-adjusted LDL levels decreased with higher
      adherence: a 10% adherence increase resulted in LDL decrease of 3.5, 5.8 and
      7.1mg/dL in low, moderate and high intensity groups. Analysis of the adherence
      effect on LDL levels adjusted for age, DM and ischemic heart disease showed that
      MPR above 80% was associated with an additional decrease in LDL levels only in
      the high intensity group. CONCLUSIONS: Increased adherence to statins beyond an
      MPR of 80% improves LDL levels only among patients given high intensity therapy.
      Switching from lower to higher intensity therapy may be more effective than
      further efforts to increase adherence.

PMID- 25770074
TI  - Decline of the lung function and quality of glycemic control in type 2 diabetes
      mellitus.
AB  - OBJECTIVE: The aim of this study was to verify to which extent in type 2 diabetes
      mellitus respiratory function and respiratory muscle efficiency decline over time
      in relation to the quality of glycemic control (GC). METHODS: Forty-five non
      smoker diabetic patients without pulmonary diseases performed a complete
      respiratory function assessment at baseline and after a follow-up of 4.9+/-0.6
      years. The respiratory muscle efficiency was assessed by maximal inspiratory
      pressure (MIP) and maximum voluntary ventilation (MVV). Patients with an average
      yearly value of glycosylated hemoglobin>=7.5% at least in two years during follow
      up were considered to have a poor GC. RESULTS: Residual volume and pulmonary
      diffusing capacity significantly declined over time in the whole sample of
      patients (p=0.049 and 0.025, respectively), but without difference between
      patients with poor (n. 12) and good (n. 33) GC. MIP declined in patients with
      poor GC (from 83.75+/-32.42 to 71.16+/-30.43% pred), and increased in those with
      good GC (from 76.22+/-26.00 to 82.42+/-30.34% pred), but the difference between
      groups was not significant (p=0.091). Finally, MVV significantly declined in
      patients with poor GC (from 70.60+/-25.49 to 68.10+/-18.82% pred) and increased
      in those with good GC (from 66.40+/-20.39 to 84.00+/-23.09% pred) with a
      significant difference between the two groups (p=0.003). CONCLUSION: These
      results show that, in type 2 diabetic patients, respiratory muscle efficiency,
      but not lung volumes and diffusing capacity, might suffer from a poor GC over
      time.

PMID- 25770075
TI  - Larval development of the pedunculate barnacles Octolasmis angulata Aurivillius
      1894 and Octolasmis cor Aurivillius 1892 (Cirripedia: Thoracica: Poecilasmatidae)
      from the gills of the mud crab, Scylla tranquebarica Fabricius, 1798.
AB  - Detailed studies of larval development of Octolasmis angulata and Octolasmis cor
      are pivotal in understanding the larval morphological evolution as well as
      enhancing the functional ecology. Six planktotrophic naupliar stages and one non
      feeding cyprid stage are documented in details for the first time for the two
      species of Octolasmis. Morphologically, the larvae of O. angulata and O. cor are
      similar in body size, setation patterns on the naupliar appendages, labrum,
      dorsal setae-pores, frontal horns, cyprid carapace, fronto-lateral gland pores,
      and lattice organs. Numbers of peculiarities were observed on the gnathobases of
      the antennae and mandible throughout the naupliar life-cycle. The setation
      pattern on the naupliar appendages are classified based on the segmentation on
      the naupliar appendages. The nauplius VI of both species undergoes a conspicuous
      change before metamorphosis into cyprid stage. The cyprid structures begin to
      form and modify beneath the naupliar body towards the end of stage VI. This study
      emphasises the importance of the pedunculate barnacle larval developmental
      studies not only to comprehend the larval morphological evolution but also to
      fill in the gaps in understanding the modification of the naupliar structures to
      adapt into the cyprid life-style.

PMID- 25770076
TI  - Pasteurized Donor Human Milk Maintains Microbiological Purity for 4 Days at 4
      degrees C.
AB  - BACKGROUND: Most protective components in human milk are stable during prolonged
      storage at 4oC; however, pasteurization reduces some microbicidal activities
      responsible for suppressing microbial growth and protecting against infection.
      Donor milk used by neonatal intensive care units (NICUs) is frozen pasteurized
      donor human milk (PDHM) defrosted and stored at 4oC. Current Human Milk Banking
      Association of North America (HMBANA) Best Practice guidelines recommend that
      milk be discarded 24 hours after being thawed, but experimental data on the
      duration of microbiological purity in thawed PDHM are sparse. OBJECTIVE: This
      study evaluates microbiological purity of thawed PDHM during prolonged storage at
      4oC. METHODS: A total of 42 independent, randomly selected PDHM samples were
      thawed at 4oC. As is typical in NICUs, each bottle was opened at 3-hour intervals
      and 3 mL was withdrawn with a sterile syringe and transferred into a sterile
      tube. The 3 mL samples removed at 0, 24, 48, 72, 96 hours, and 9 days were tested
      for the presence of any microorganisms by a clinical laboratory that routinely
      screens PDHM for microbes. RESULTS: No evidence of microbial growth was observed
      in cultured samples taken at 0 to 9 days after thawing of the milk samples.
      CONCLUSION: There was no evidence of microbes in PDHM as dispensed by HMBANA milk
      banks when defrosted and stored at 4oC for up to 9 days. Extended storage of PDHM
      in the NICU could reduce waste of donor milk, thereby increasing availability of
      human milk to vulnerable neonatal patients.

PMID- 25770077
TI  - Major health committee report falls victim to MPs' disagreement.

PMID- 25770078
TI  - Investigating the phenomenon of "cognitive-motor interference" in multiple
      sclerosis by means of dual-task posturography.
AB  - BACKGROUND: Two simultaneously performed tasks may compete for common brain
      network resources in patients with multiple sclerosis (MS), suggesting the
      occurrence of a cognitive-motor interference. While this phenomenon has been well
      described for walking and gait, data on static balance are scarce. METHODS: In
      this cross-sectional study, 92 patients and 46 sex/age-matched healthy controls
      (HCs) were tested by means of static posturography under eyes opened (single-task
      condition) and while performing the Stroop word-colour task (dual-task
      condition), to estimate the dual-task cost (DTC) of standing balance. The patient
      group also underwent the Expanded Disability Status Scale, 25-foot walking test,
      12-item MS walking scale, Modified Fatigue Impact Scale, and Symbol Digit
      Modalities Test. RESULTS: Patients had larger postural sway under both single
      task and dual-task conditions (p<0.001), as well as greater DTC of standing
      balance (p=0.021) than HCs. Although secondary progressive (SP) patients had
      larger sway in both conditions than relapsing-remitting (RR) patients (p<0.05),
      these latter ones exhibited a greater DTC of postural balance (p=0.045). Deficits
      in sustained attention and information processing speed, as assessed by the SDMT,
      were also independently associated with the magnitude of DTC of standing balance
      (p=0.005). CONCLUSIONS: The phenomenon of cognitive-motor interference might be
      unmasked by a dual-task posturography and was associated with impaired sustained
      attention and information processing speed, especially in RR patients. The
      smaller DTC of standing balance observed in SP patients may be due to the ceiling
      effect of postural sway, or alternatively to the lack of postural reserve which
      constrained the more disabled patients to prioritize the balance over the
      cognitive task.

PMID- 25770079
TI  - Limb contribution to increased self-selected walking speeds during body weight
      support in individuals poststroke.
AB  - Individuals poststroke walk at faster self-selected speeds under some nominal
      level of body weight support (BWS) whereas nonimpaired individuals walk slower
      after adding BWS. The purpose of this study was to determine whether increases in
      self-selected overground walking speed under BWS conditions of individuals
      poststroke can be explained by changes in their paretic and nonparetic ground
      reaction forces (GRF). We hypothesize that increased self-selected walking speed,
      recorded at some nominal level of BWS, will relate to decreased braking GRFs by
      the paretic limb. We recruited 10 chronic (>12 months post-ictus, 57.5+/-9.6
      y.o.) individuals poststroke and eleven nonimpaired participants (53.3+/-4.1
      y.o.). Participants walked overground in a robotic device, the KineAssist Walking
      and Balance Training System that provided varying degrees of BWS (0-20% in 5%
      increments) while individuals self-selected their walking speed. Self-selected
      walking speed and braking and propulsive GRF impulses were quantified. Out of 10
      poststroke individuals, 8 increased their walking speed 13% (p=0.004) under some
      level of BWS (5% n=2, 10% n=3, 20% n=3) whereas nonimpaired controls did not
      change speed (p=0.470). In individuals poststroke, changes to self-selected
      walking speed were correlated with changes in paretic propulsive impulses
      (r=0.68, p=0.003) and nonparetic braking impulses (r=-0.80, p=0.006), but were
      not correlated with decreased paretic braking impulses (r=0.50 p=0.14). This
      investigation demonstrates that when individuals poststroke are provided with BWS
      and allowed to self-select their overground walking speed, they are capable of
      achieving faster speeds by modulating braking impulses on the nonparetic limb and
      propulsive impulses of the paretic limb. 

PMID- 25770080
TI  - Inhibition of mTOR pathway restrains astrocyte proliferation, migration and
      production of inflammatory mediators after oxygen-glucose deprivation and
      reoxygenation.
AB  - Glial scar is a major impediment to axonal regeneration in central nervous system
      (CNS) disorders. Overcoming this physical and biochemical barrier might be
      crucial for axonal regeneration and functional compensation during the
      progression of CNS disorders. The mammalian target of rapamycin (mTOR) is an
      evolutionarily conserved serine/threonine kinase, involved in process of cell
      proliferation, migration, autophagy and protein synthesis. Rapamycin, an
      inhibitor of mTOR signaling, can exert neuroprotective effects in several CNS
      diseases. However, its role in the process of reactive astrogliosis including
      cell proliferation, migration and cytokine production after cerebral ischemia
      still remains largely unknown. In this study, we investigated the effects of mTOR
      blockade in cultured astrocytes exposed to oxygen-glucose
      deprivation/reoxygenation (OGD/R), a wildly used cellular ischemia model which
      mimics ideally cerebral ischemia model in vivo. We found that astrocytes became
      activated after OGD/R, characterized by change of astrocytic morphology,
      upregulation of GFAP expression, the increase number of Edu positive cells, and
      accompanied with phosphorylation of mTOR protein and its substrate S6K1.
      Rapamycin significantly inhibited mTOR signal pathway, suppressed proliferation
      of astrocytes via modulation of cell cycle progression. Moreover, rapamycin
      attenuated astrocytic migration and mitigated production of inflammatory factors
      such as TNF-alpha and iNOS induced by astrocytes exposed to OGD/R. Taken
      together, our findings indicated that mTOR blockade by rapamycin attenuates
      astrocyte migration, proliferation and production of inflammation mediators. We
      suggest that targeting mTOR pathway in astrocyte activation may represent a
      potentially new therapeutic strategy against deleterious neurotoxic processes of
      reactive astrogliosis in CNS disorders such as ischemic stroke. 

PMID- 25770081
TI  - Characterising acute coronary syndrome-associated depression: Let the data speak.
AB  - Depression in the context of acute coronary syndrome (ACS) is understood to
      confer increased morbidity and mortality risk. The pathophysiological mechanisms
      underlying this association remain poorly understood, although several candidates
      including inflammation, cardiac autonomic dysregulation, and behavioural factors
      are viewed as of key importance. No single bio-behavioural explanatory model of
      ACS-associated depression has emerged, likely due the substantial heterogeneity
      across both conditions. We studied 344 patients with ACS; 45 fulfilled diagnostic
      (DSM-IV) criteria for a major depressive episode occurring within 1-month of ACS,
      and 13 had ongoing major depression that pre-dated ACS and continued through to 1
      month post-ACS. We employed two statistical methods (multinomial logistic
      regression; and latent class analysis) and a range of immunological, autonomic
      and nutritional markers in an attempt to characterise a biological basis for ACS
      associated depression. Regression modelling failed to accurately predict
      categorical group membership of ACS-associated depression. An alternative data
      driven approach produced a three-class solution, with the derived classes
      differing on measure of C-reactive protein, vitamin D, omega-6:omega-3 ratio,
      heart rate variability, and age (all p?0.004). The majority of participants with
      ACS-associated and ongoing depression were members of the class characterised by
      the greatest biological disturbance. Patients with depression differed from those
      without depression on a range of psychological trait and state variables;
      additionally reporting poorer sleep quality, higher levels of social isolation,
      and functional impairment, but had similar biological profiles. Patients with
      ongoing depression generally had higher scores on these psychological/behavioural
      measures. Our novel analytic approach identified a combination of biomarkers
      suggestive of a role for immune, autonomic, and nutritional pathways in the
      manifestation of depression during ACS, in the context of additional psychosocial
      and behavioural vulnerabilities. Further studies are required to confirm the
      causal role of these factors in perpetuating depression and increasing risk of
      poor-health outcomes.

PMID- 25770083
TI  - NIDDK Programs and Emerging Opportunities for Digestive Diseases Research.

PMID- 25770082
TI  - Inflammation impairs social cognitive processing: A randomized controlled trial
      of endotoxin.
AB  - Neuropsychiatric disorders (e.g., autism, schizophrenia) are partially
      characterized by social cognitive deficits, including impairments in the ability
      to perceive others' emotional states, which is an aspect of social cognition
      known as theory of mind (ToM). There is also evidence that inflammation may be
      implicated in the etiology of these disorders, but experimental data linking
      inflammation to deficits in social cognition is sparse. Thus, we examined whether
      exposure to an experimental inflammatory challenge led to changes in ToM. One
      hundred and fifteen (n=115) healthy participants were randomly assigned to
      receive either endotoxin, which is an inflammatory challenge, or placebo.
      Participants completed a social cognition task, the Reading the Mind in the Eyes
      (RME) test, at baseline and at the peak of the inflammatory response for the
      endotoxin group. The RME test, a validated measure of ToM, evaluates how
      accurately participants can identify the emotional state of another person by
      looking only at their eyes. We found that endotoxin (vs. placebo) led to
      decreases in performance on the RME test from baseline to the peak of
      inflammatory response, indicating that acute inflammation can lead to decreases
      in the ability to accurately and reliably comprehend emotional information from
      others. Given that deficits in ToM are implicated in neuropsychiatric disorders,
      including those which may have an inflammatory basis, these results may have
      implications for understanding the links between inflammation, social cognition,
      and neuropsychiatric disorders. CLINICAL TRIALS REGISTRATION: ClinicalTrials.gov
      NCT01671150.

PMID- 25770084
TI  - Endoscopic ultrasonography-guided fine needle aspiration of kidney masses.

PMID- 25770085
TI  - Impact of age on outcomes following continuous-flow left ventricular assist
      device implantation.
AB  - OBJECTIVES: The goal of our study was to analyse the impact of age on outcomes in
      patients who underwent continuous-flow left ventricular assist device (CF-LVAD)
      placement at our institution. METHODS: One hundred and twenty-eight patients were
      implanted with a CF-LVAD between January 2008 and June 2014. Eighty-five patients
      were implanted with the device as a bridge to transplant (BTT); the remaining (n
      = 43) were on destination therapy (DT). Each group was divided into patients <65
      years old and >= 65 years old at device implantation. Patients were followed up
      for at least 24 months or until transplant or death. RESULTS: Eighty-five
      patients (66%) received a CF-LVAD as BTT. Patients >= 65 years old (n = 8) had a
      lower preoperative cardiac index and prothrombin time-international normalized
      ratio (P = 0.009), and a longer stay in the intensive care unit (P = 0.008).
      Adverse events including infections, re-exploration for bleeding, ischaemic and
      haemorrhagic stroke, renal failure and right heart failure were comparable in
      both age groups. Eighty-two percent (n = 63) of the young patients and 75% (n =
      6) of the older patients, who were on LVAD as BTT, underwent heart transplant
      within the first 24 months of LVAD implantation. Overall survival at 3, 6, 12 and
      24 months were 95, 95, 77 and 70%, respectively, post-CF-LVAD implantation as BTT
      for the younger group and 73% for the older group at 3, 6 and 12 months (P =
      0.35). Forty-three patients (34%) received a CF-LVAD as DT. Patients >= 65 years
      old (n = 14) on DT had a higher incidence of peripheral vascular disease (P =
      0.048), higher serum sodium (P = 0.004) and serum creatinine values (P = 0.002),
      preoperatively. There were more strokes in the older patients post-LAVD
      implantation (14 vs 0%; P = 0.048). Overall survival at 3, 6, 12 and 24 months
      were 85, 79, 75 and 62%, respectively, for the younger group and 93, 77, 67 and
      34% for the older group, respectively (P = 0.26). CONCLUSIONS: This study
      demonstrates that LVAD therapy can be used in the older patients with acceptable
      mortality and morbidity, and age alone should not be used as the sole criterion
      for exclusion from LVAD implantation.

PMID- 25770086
TI  - Post-PET ultrasound improves specificity of 18F-FDG-PET for recurrent
      differentiated thyroid cancer while maintaining sensitivity.
AB  - BACKGROUND: Positron emission tomography (PET) using fluor-18-deoxyglucose (18F
      FDG) with or without computed tomography (CT) is generally accepted as the most
      sensitive imaging modality for diagnosing recurrent differentiated thyroid cancer
      (DTC) in patients with negative whole body scintigraphy with iodine-131 (I-131).
      PURPOSE: To assess the potential incremental value of ultrasound (US) over 18F
      FDG-PET-CT. MATERIAL AND METHODS: Fifty-one consecutive patients with suspected
      recurrent DTC were prospectively evaluated using the following multimodal imaging
      protocol: (i) US before PET (pre-US) with or without fine needle biopsy (FNB) of
      suspicious lesions; (ii) single photon emission computed tomography (>=3 GBq I
      131) with co-registered CT (SPECT-CT); (iii) 18F-FDG-PET with co-registered
      contrast-enhanced CT of the neck; (iv) US in correlation with the other imaging
      modalities (post-US). Postoperative histology, FNB, and long-term follow-up
      (median, 2.8 years) were taken as composite gold standard. RESULTS: Fifty-eight
      malignant lesions were identified in 34 patients. Forty lesions were located in
      the neck or upper mediastinum. On receiver operating characteristics (ROC)
      analysis, 18F-FDG-PET had a limited lesion-based specificity of 59% at a set
      sensitivity of 90%. Pre-US had poor sensitivity and specificity of 52% and 53%,
      respectively, increasing to 85% and 94% on post-US, with knowledge of the PET/CT
      findings (P < 0.05 vs. PET and pre-US). Multimodal imaging changed therapy in 15
      out of 51 patients (30%). CONCLUSION: In patients with suspected recurrent DTC,
      supplemental targeted US in addition to 18F-FDG-PET-CT increases specificity
      while maintainin sensitivity, as non-malignant FDG uptake in cervical lesions can
      be confirmed.

PMID- 25770087
TI  - Explaining Extremity in Evaluation of Group Members: Meta-Analytic Tests of Three
      Theories.
AB  - A meta-analysis that included more than 1,100 effect sizes tested the predictions
      of three theoretical perspectives that explain evaluative extremity in social
      judgment: complexity-extremity theory, subjective group dynamics model, and
      expectancy-violation theory. The work seeks to understand the ways in which group
      based information interacts with person-based information to influence extremity
      in evaluations. Together, these three theories point to the valence of person
      based information, group membership of the evaluated targets relative to the
      evaluator, status of the evaluators' ingroup, norm consistency of the person
      based information, and incongruency of person-based information with stereotype
      based expectations as moderators. Considerable support, but some limiting
      conditions, were found for each theoretical perspective. Implications of the
      results are discussed. 

PMID- 25770089
TI  - Private firms enlisted to cut waiting lists for tests and surgery in L780m
      contract.

PMID- 25770091
TI  - VisualCNA: a GUI for interactive constraint network analysis and protein
      engineering for improving thermostability.
AB  - Constraint network analysis (CNA) is a graph theory-based rigidity analysis
      approach for linking a biomolecule's structure, flexibility, (thermo)stability
      and function. Results from CNA are highly information-rich and require intuitive,
      synchronized and interactive visualization for a comprehensive analysis. We
      developed VisualCNA, an easy-to-use PyMOL plug-in that allows setup of CNA runs
      and analysis of CNA results linking plots with molecular graphics
      representations. From a practical viewpoint, the most striking feature of
      VisualCNA is that it facilitates interactive protein engineering aimed at
      improving thermostability. AVAILABILITY AND IMPLEMENTATION: VisualCNA and its
      dependencies (CNA and FIRST software) are available free of charge under GPL and
      academic licenses, respectively. VisualCNA and CNA are available at
      http://cpclab.uni-duesseldorf.de/software; FIRST is available at
      http://flexweb.asu.edu.

PMID- 25770090
TI  - The role of 'hidden' community volunteers in community-based health service
      delivery platforms: examples from sub-Saharan Africa.
AB  - Community-based research on child survival in sub-Saharan Africa has focussed on
      the increased provision of curative health services by a formalised cadre of lay
      community health workers (CHWs), but we have identified a particular
      configuration, that deserves closer scrutiny. We identified a two-tiered CHW
      system, with the first tier being the lessor known or 'hidden' community/village
      level volunteers and the second tier being formal, paid CHWs, in Ethiopia, Mali,
      and Niger. Whilst the disease-focussed tasks of the formal CHW tier may be more
      amenable to classic epidemiological surveillance, we postulate that understanding
      the relationship between formalised CHWs and volunteer cadres, in terms of scope,
      location of practice and ratio to population, would be important for a
      comprehensive evaluation of child survival in these countries. We report on the
      findings from our joint qualitative and quantitative investigations, highlighting
      the need to recognise the 'hidden' contribution of volunteers. We need to better
      characterize the volunteers' interaction with community-based and primary care
      services and to better understand ways to improve the volunteer systems with the
      right type of investments. This is particularly important for considering the
      models for scale-up of CHWs in sub-Saharan Africa. 

PMID- 25770088
TI  - A recent bottleneck of Y chromosome diversity coincides with a global change in
      culture.
AB  - It is commonly thought that human genetic diversity in non-African populations
      was shaped primarily by an out-of-Africa dispersal 50-100 thousand yr ago (kya).
      Here, we present a study of 456 geographically diverse high-coverage Y chromosome
      sequences, including 299 newly reported samples. Applying ancient DNA
      calibration, we date the Y-chromosomal most recent common ancestor (MRCA) in
      Africa at 254 (95% CI 192-307) kya and detect a cluster of major non-African
      founder haplogroups in a narrow time interval at 47-52 kya, consistent with a
      rapid initial colonization model of Eurasia and Oceania after the out-of-Africa
      bottleneck. In contrast to demographic reconstructions based on mtDNA, we infer a
      second strong bottleneck in Y-chromosome lineages dating to the last 10 ky. We
      hypothesize that this bottleneck is caused by cultural changes affecting variance
      of reproductive success among males. 

PMID- 25770092
TI  - Enhanced Natriuresis and Diuresis in Wistar Rats Caused by the Costimulation of
      Renal Dopamine D3 and Angiotensin II Type 2 Receptors.
AB  - BACKGROUND: The kidney, via its regulation of sodium excretion, which is
      modulated by humoral factors, including the dopamine and renin-angiotensin
      systems, keeps the blood pressure in the normal range. We have reported a
      negative interaction between dopamine D3 and AT1 receptors (D3R and AT1R) in
      renal proximal tubule (RPT) cells. Here, we studied the interaction between D3R
      and AT2R in vitro and in vivo. METHODS AND RESULTS: Stimulation of either the D3R
      or AT2R, by the intrarenal arterial infusion of PD128907, a D3R agonist, or
      CGP42112A, an AT2R agonist, induced natriuresis and diuresis that were enhanced
      by the simultaneous infusion of PD128907 and CGP42112A in Wistar rats. The D3/AT2
      receptor interaction was confirmed in in vitro, i.e., stimulation of either the
      D3R or AT2R inhibited Na(+)-K(+)-ATPase activity that was enhanced by the
      costimulation of these receptors. D3R and AT2R colocalized and
      coimmunoprecipitated in kidney and RPT cells (RPTCs). Stimulation of one receptor
      increased the localization of the other receptor at the plasma cell membrane.
      ERK1/2-MAPK is involved in the signaling pathway of D3R and AT2R interaction
      because costimulation of D3R and AT2R significantly increased ERK1/2-MAPK
      expression in RPTCs; inhibition of ERK1/2-MAPK abolished the inhibition of Na(+)
      K(+)-ATPase activity that was enhanced by D3R and AT2R costimulation.
      CONCLUSIONS: Our current study indicates that D3R, in combination with AT2R,
      enhances natriuresis and diuresis, via ERK1/2-MAPK pathway, that may be involved
      in the regulation of blood pressure.

PMID- 25770093
TI  - A role for whey acidic protein four-disulfide-core 12 (WFDC12) in the regulation
      of the inflammatory response in the lung.
AB  - INTRODUCTION: Secretory leucocyte protease inhibitor and elafin are members of
      the whey acidic protein (WAP), or WAP four disulfide-core (WFDC), family of
      proteins and have multiple contributions to innate defence including inhibition
      of neutrophil serine proteases and inhibition of the inflammatory response to
      lipopolysaccharide (LPS). This study aimed to explore potential activities of
      WFDC12, a previously uncharacterised WFDC protein expressed in the lung. METHODS:
      Recombinant expression and purification of WFDC12 were optimised in Escherichia
      coli. Antiprotease, antibacterial and immunomodulatory activities of recombinant
      WFDC12 were evaluated and levels of endogenous WFDC12 protein were characterised
      by immunostaining and ELISA. RESULTS: Recombinant WFDC12 inhibited cathepsin G,
      but not elastase or proteinase-3 activity. Monocytic cells pretreated with
      recombinant WFDC12 before LPS stimulation produced significantly lower levels of
      the pro-inflammatory cytokines interleukin-8 and monocyte chemotactic protein-1
      compared with cells stimulated with LPS alone. Recombinant WFDC12 became
      conjugated to fibronectin in a transglutaminase-mediated reaction and retained
      antiprotease activity. In vivo WFDC12 expression was confirmed by immunostaining
      of human lung tissue sections. WFDC12 levels in human bronchoalveolar lavage
      fluid from healthy and lung-injured patients were quantitatively compared,
      showing WFDC12 to be elevated in both patients with acute respiratory distress
      syndrome and healthy subjects treated with LPS, relative to healthy controls.
      CONCLUSIONS: Together, these results suggest a role for this lesser known WFDC
      protein in the regulation of lung inflammation.

PMID- 25770095
TI  - Utilizing the Plateau-Rayleigh Instability with Heat-Driven Nano-Biosensing
      Systems.
AB  - Plateau-Rayleigh instability describes the infinite falling stream of fluid
      breaks into smaller droplets. With the development of nanotechnology, more and
      more attention is being drawn to Plateau-Rayleigh instability. This surface
      tension-driven instability performs well in the preparation of the nanoparticles,
      especially in photonics applications, such as optical micro-resonators in nano
      biosensing systems. In this article, we mainly adopt the thermal fluid coupling
      method. The effect of temperature field on instability is studied with the aid of
      numerical simulation. In addition, the radius of the inner fluid column, the
      thickness of the outer fluid, and the temperature gradient are also studied to
      explore how the factors influence the Plateau-Rayleigh instability. The
      wavelength of the instability is characterized by droplet diameter, which is
      formed through the process caused by Plateau-Rayleigh instability. 

PMID- 25770094
TI  - The heritability of leucocyte telomere length dynamics.
AB  - BACKGROUND: Leucocyte telomere length (LTL) is a complex trait associated with
      ageing and longevity. LTL dynamics are defined by LTL and its age-dependent
      attrition. Strong, but indirect evidence suggests that LTL at birth and its
      attrition during childhood largely explains interindividual LTL variation among
      adults. A number of studies have estimated the heritability of LTL, but none has
      assessed the heritability of age-dependent LTL attrition. METHODS: We examined
      the heritability of LTL dynamics based on a longitudinal evaluation (an average
      follow-up of 12 years) in 355 monozygotic and 297 dizygotic same-sex twins (aged
      19-64 years at baseline). RESULTS: Heritability of LTL at baseline was estimated
      at 64% (95% CI 39% to 83%) with 22% (95% CI 6% to 49%) of shared environmental
      effects. Heritability of age-dependent LTL attrition rate was estimated at 28%
      (95% CI 16% to 44%). Individually unique environmental factors, estimated at 72%
      (95% CI 56% to 84%) affected LTL attrition rate with no indication of shared
      environmental effects. CONCLUSIONS: This is the first study that estimated
      heritability of LTL and also its age-dependent attrition. As LTL attrition is
      much slower in adults than in children and given that having a long or a short
      LTL is largely determined before adulthood, our findings suggest that
      heritability and early life environment are the main determinants of LTL
      throughout the human life course. Thus, insights into factors that influence LTL
      at birth and its dynamics during childhood are crucial for understanding the role
      of telomere genetics in human ageing and longevity.

PMID- 25770096
TI  - EU-US trade treaty threatens vital health gains, warn public health experts.

PMID- 25770097
TI  - Lived experiences of multimorbidity: An interpretative meta-synthesis of
      patients', general practitioners' and trainees' perceptions.
AB  - OBJECTIVES: Multimorbidity is an increasing challenge. Better understanding of
      lived experiences of patients, general practitioners and trainees, may advance
      patient care and medical education. This interpretative meta-synthesis sought to
      (i) understand lived experiences of patients, general practitioners and trainees
      regarding multimorbidity, (ii) identify how similarities and differences in
      experiences should shape future solutions. METHODS: Empirical studies containing
      qualitative data and pertaining to lived experiences from our recent realist
      synthesis (PROSPERO 2013:CRD42013003862) were included. Following quality
      assessment, data were extracted from key studies to build an integrated analytic
      framework. Data from remaining studies were utilised to expand and refine the
      framework through thematic analysis of concepts within and between perspectives.
      RESULTS: Twenty-one papers were included in the meta-synthesis. Analysis of 70
      concepts produced five themes: (1) goals of care and decision making, (2)
      complexity, (3) meeting expectations, (4) logistics and (5) interpersonal
      dynamics. The complexities of multimorbidity lead to shared feelings of
      vulnerability, uncertainty and enforced compromises. Barriers to optimal care
      education included system constraints, inadequate continuity and role
      uncertainty. DISCUSSION: There was little evidence of shared discussion of these
      challenges. Addressing these issues and more explicit exploration of the
      experiences of each group during interactions may improve delivery and
      satisfaction in care and education.

PMID- 25770098
TI  - Can Atypical Antipsychotic Augmentation Reduce Subsequent Treatment Failure More
      Effectively Among Depressed Patients with a Higher Degree of Treatment
      Resistance? A Meta-Analysis of Randomized Controlled Trials.
AB  - BACKGROUND: Atypical antipsychotic augmentation was demonstrated to be
      efficacious in treatment-resistant depression (TRD) in previous meta-analyses. We
      investigate whether there are differences in the effect size of atypical
      antipsychotic augmentation in major depressive disorder according to the degree
      of treatment resistance. METHODS: A comprehensive search of four databases
      identified 11 randomized controlled trials. The 11 trials, which included 3 341
      participants, were pooled using a random-effects meta-analysis. RESULTS: Atypical
      antipsychotic augmentation of antidepressant therapy showed superior efficacy
      compared to antidepressant monotherapy in TRD in terms of both response and
      remission rates (response, risk ratio [RR] = 1.38, 95% confidence interval [CI] =
      1.25 to 1.53; remission, RR = 1.62, 95% CI = 1.42 to 1.85). In addition,
      regarding response rates in the TRD trials, atypical antipsychotic augmentation
      exhibited significantly different effect sizes according to the degree of
      treatment resistance (TRD 1: RR = 1.24; TRD 2: RR = 1.37; TRD 2-4: RR = 1.58). In
      non-TRD trials, atypical antipsychotic augmentation failed to show superior
      efficacy over antidepressant monotherapy in terms of remission rates (RR = 0.89;
      95% CI = 0.69 to 1.14). Atypical antipsychotic augmentation of antidepressant
      therapy exhibits greater effect size in patients with a higher degree of
      treatment resistance. CONCLUSIONS: This finding strengthens the rationale for
      considering atypical antipsychotic augmentation among depressed patients with
      multiple previous treatment failures in clinical practice. The efficacy of
      atypical antipsychotic augmentation for non-TRD seems to be different from that
      for TRD and, thus, further studies of non-TRD populations are needed.

PMID- 25770099
TI  - When does cognitive functioning peak? The asynchronous rise and fall of different
      cognitive abilities across the life span.
AB  - Understanding how and when cognitive change occurs over the life span is a
      prerequisite for understanding normal and abnormal development and aging. Most
      studies of cognitive change are constrained, however, in their ability to detect
      subtle, but theoretically informative life-span changes, as they rely on either
      comparing broad age groups or sparse sampling across the age range. Here, we
      present convergent evidence from 48,537 online participants and a comprehensive
      analysis of normative data from standardized IQ and memory tests. Our results
      reveal considerable heterogeneity in when cognitive abilities peak: Some
      abilities peak and begin to decline around high school graduation; some abilities
      plateau in early adulthood, beginning to decline in subjects' 30s; and still
      others do not peak until subjects reach their 40s or later. These findings
      motivate a nuanced theory of maturation and age-related decline, in which
      multiple, dissociable factors differentially affect different domains of
      cognition. 

PMID- 25770100
TI  - Genome-wide association study based on multiple imputation with low-depth
      sequencing data: application to biofuel traits in reed canarygrass.
AB  - Genotyping by sequencing allows for large-scale genetic analyses in plant species
      with no reference genome, but sets the challenge of sound inference in presence
      of uncertain genotypes. We report an imputation-based genome-wide association
      study (GWAS) in reed canarygrass (Phalaris arundinacea L., Phalaris caesia Nees),
      a cool-season grass species with potential as a biofuel crop. Our study involved
      two linkage populations and an association panel of 590 reed canarygrass
      genotypes. Plants were assayed for up to 5228 single nucleotide polymorphism
      markers and 35 traits. The genotypic markers were derived from low-depth
      sequencing with 78% missing data on average. To soundly infer marker-trait
      associations, multiple imputation (MI) was used: several imputes of the marker
      data were generated to reflect imputation uncertainty and association tests were
      performed on marker effects across imputes. A total of nine significant markers
      were identified, three of which showed significant homology with the Brachypodium
      dystachion genome. Because no physical map of the reed canarygrass genome was
      available, imputation was conducted using classification trees. In general, MI
      showed good consistency with the complete-case analysis and adequate control over
      imputation uncertainty. A gain in significance of marker effects was achieved
      through MI, but only for rare cases when missing data were <45%. In addition to
      providing insight into the genetic basis of important traits in reed canarygrass,
      this study presents one of the first applications of MI to genome-wide analyses
      and provides useful guidelines for conducting GWAS based on genotyping-by
      sequencing data. 

PMID- 25770101
TI  - Tight regulation of the unfolded protein sensor Ire1 by its intramolecularly
      antagonizing subdomain.
AB  - Accumulation of unfolded proteins in the endoplasmic reticulum (ER) accompanies
      ER stress and causes the type-I transmembrane protein Ire1 (also known as ERN1)
      to trigger the unfolded protein response (UPR). When dimerized, the core stress
      sensing region (CSSR) of Ire1 directly captures unfolded proteins and forms a
      high-order oligomer, leading to clustering and activation of Ire1. The CSSR is N
      terminally flanked by an intrinsically disordered subdomain, which we previously
      named Subregion I, in Saccharomyces cerevisiae Ire1. In this study, we describe
      tight repression of Ire1 activity by Subregion I under conditions of no or weak
      stress. Weak hyperactivation of an Ire1 mutant lacking Subregion I slightly
      retarded growth of yeast cells cultured under unstressed conditions. Fungal Ire1
      orthologs and the animal Ire1 family protein PERK (also known as EIF2AK3) carry N
      terminal intrinsically disordered subdomains with a similar structure and
      function to that of Subregion I. Our observations presented here cumulatively
      indicate that Subregion I is captured by the CSSR as an unfolded protein
      substrate. This intramolecular subdomain interaction is likely to compromise self
      association of the CSSR, explaining why Subregion I can suppress Ire1 activity
      when ER-accumulated unfolded proteins are not abundant. 

PMID- 25770102
TI  - Pyruvate kinase M2 at a glance.
AB  - Reprogrammed metabolism is a key feature of cancer cells. The pyruvate kinase M2
      (PKM2) isoform, which is commonly upregulated in many human cancers, has been
      recently shown to play a crucial role in metabolism reprogramming, gene
      transcription and cell cycle progression. In this Cell Science at a glance
      article and accompanying poster, we provide a brief overview of recent advances
      in understanding the mechanisms underlying the regulation of PKM2 expression,
      enzymatic activity, metabolic functions and subcellular location. We highlight
      the instrumental role of the non-metabolic functions of PKM2 in tumorigenesis and
      evaluate the potential to target PKM2 for cancer treatment. 

PMID- 25770103
TI  - HBV secretion is regulated through the activation of endocytic and autophagic
      compartments mediated by Rab7 stimulation.
AB  - The cellular mechanisms by which hepatitis B virus (HBV) is assembled and
      exported are largely undefined. Recently, it has been suggested that these steps
      require the multivesicular body (MVB) and the autophagic machinery. However, the
      mechanisms by which HBV might regulate these compartments are unclear. In this
      study, we have found that by activating Rab7a, HBV alters its own secretion by
      inducing dramatic changes in the morphology of MVB and autophagic compartments.
      These changes are characterized by the formation of numerous tubules that are
      dependent upon the increase in Rab7 activity observed in the HBV-expressing
      HepG2.2.15 cells compared to HepG2 cells. Interestingly, transfection-based
      expression of the five individual viral proteins indicated that the precore
      protein, which is a precursor of HBeAg, was largely responsible for the increased
      Rab7 activity. Finally, small interfering RNA (siRNA)-mediated depletion of Rab7
      significantly increased the secretion of virions, suggesting that reduced
      delivery of the virus to the lysosome facilitates viral secretion. These findings
      provide novel evidence indicating that HBV can regulate its own secretion through
      an activation of the endo-lysosomal and autophagic pathway mediated by Rab7
      activation. 

PMID- 25770105
TI  - Former editor pays $1m to settle allegations of kickbacks to promote products.

PMID- 25770104
TI  - Bit-1 is an essential regulator of myogenic differentiation.
AB  - Muscle differentiation requires a complex signaling cascade that leads to the
      production of multinucleated myofibers. Genes regulating the intrinsic
      mitochondrial apoptotic pathway also function in controlling cell
      differentiation. How such signaling pathways are regulated during differentiation
      is not fully understood. Bit-1 (also known as PTRH2) mutations in humans cause
      infantile-onset multisystem disease with muscle weakness. We demonstrate here
      that Bit-1 controls skeletal myogenesis through a caspase-mediated signaling
      pathway. Bit-1-null mice exhibit a myopathy with hypotrophic myofibers. Bit-1
      null myoblasts prematurely express muscle-specific proteins. Similarly, knockdown
      of Bit-1 expression in C2C12 myoblasts promotes early differentiation, whereas
      overexpression delays differentiation. In wild-type mice, Bit-1 levels increase
      during differentiation. Bit-1-null myoblasts exhibited increased levels of
      caspase 9 and caspase 3 without increased apoptosis. Bit-1 re-expression
      partially rescued differentiation. In Bit-1-null muscle, Bcl-2 levels are
      reduced, suggesting that Bcl-2-mediated inhibition of caspase 9 and caspase 3 is
      decreased. Bcl-2 re-expression rescued Bit-1-mediated early differentiation in
      Bit-1-null myoblasts and C2C12 cells with knockdown of Bit-1 expression. These
      results support an unanticipated yet essential role for Bit-1 in controlling
      myogenesis through regulation of Bcl-2. 

PMID- 25770106
TI  - Morphological and immunohistochemical analyses of soluble proteins in mucous
      membranes of living mouse intestines by cryotechniques.
AB  - We have performed immunohistochemical or ultrastructural analyses of living mouse
      small intestines using Epon blocks prepared by 'in vivo cryotechnique' (IVCT). By
      electron microscopy, intracellular ultrastructures of epithelial cells were well
      preserved in tissue areas 5-10 MUm away from cryogen-contact surface tissues.
      Their microvilli contained dynamically waving actin filaments, and highly
      electron-dense organelles, such as mitochondria, were seen under the widely
      organized terminal web. By quick-freezing of fresh resected tissues (FT-QF), many
      erythrocytes were congested within blood vessels due to loss of blood pressure.
      By immersion-fixation (IM-DH) and perfusion-fixation (PF-DH), small vacuoles were
      often seen in the cytoplasm of epithelial cells, and their intercellular spaces
      were also dilated. Moreover, actin filament bundles were irregular in cross
      sections of microvilli, compared with those with IVCT. Epon-embedded thick
      sections were treated with sodium ethoxide, followed by antigen retrieval and
      immunostained for immunoglobulin A (IgA), Ig kappa light chain (Igkappa), J-chain
      and albumin. By cryotechniques, IgA immunoreactivity was detected as tiny dot
      like patterns in cytoplasm of some epithelial cells. Both J-chain and Igkappa
      immunoreactivities were detected in the same local areas as those of IgA. By FT
      QF, however, the IgA immunoreactivity was more weakly detected, compared with
      that with IVCT. In thick sections prepared by IM-DH and PF-DH, it was rarely
      observed in both plasma and epithelial cells. Another albumin was diffusely
      immunolocalized in extracellular matrices of mucous membranes and also within
      blood vessels. Thus, IVCT was useful for preservation of soluble proteins and
      ultrastructural analyses of dynamically changing epithelial cells of living mouse
      small intestines. 

PMID- 25770108
TI  - Downstream of a kinase cascade: a trihelix transcription factor represses immune
      genes.

PMID- 25770107
TI  - Identification and mode of inheritance of quantitative trait loci for secondary
      metabolite abundance in tomato.
AB  - A large-scale metabolic quantitative trait loci (mQTL) analysis was performed on
      the well-characterized Solanum pennellii introgression lines to investigate the
      genomic regions associated with secondary metabolism in tomato fruit pericarp. In
      total, 679 mQTLs were detected across the 76 introgression lines. Heritability
      analyses revealed that mQTLs of secondary metabolism were less affected by
      environment than mQTLs of primary metabolism. Network analysis allowed us to
      assess the interconnectivity of primary and secondary metabolism as well as to
      compare and contrast their respective associations with morphological traits.
      Additionally, we applied a recently established real-time quantitative PCR
      platform to gain insight into transcriptional control mechanisms of a subset of
      the mQTLs, including those for hydroxycinnamates, acyl-sugar, naringenin
      chalcone, and a range of glycoalkaloids. Intriguingly, many of these compounds
      displayed a dominant-negative mode of inheritance, which is contrary to the
      conventional wisdom that secondary metabolite contents decreased on
      domestication. We additionally performed an exemplary evaluation of two candidate
      genes for glycolalkaloid mQTLs via the use of virus-induced gene silencing. The
      combined data of this study were compared with previous results on primary
      metabolism obtained from the same material and to other studies of natural
      variance of secondary metabolism. 

PMID- 25770110
TI  - Uncovering the unexpected site of biosynthesis of a major cell wall component in
      grasses.

PMID- 25770109
TI  - Phosphorylation of trihelix transcriptional repressor ASR3 by MAP KINASE4
      negatively regulates Arabidopsis immunity.
AB  - Proper control of immune-related gene expression is crucial for the host to
      launch an effective defense response. Perception of microbe-associated molecular
      patterns (MAMPs) induces rapid and profound transcriptional reprogramming via
      unclear mechanisms. Here, we show that ASR3 (ARABIDOPSIS SH4-RELATED3) functions
      as a transcriptional repressor and plays a negative role in regulating pattern
      triggered immunity (PTI) in Arabidopsis thaliana. ASR3 belongs to a plant
      specific trihelix transcription factor family for which functional studies are
      lacking. MAMP treatments induce rapid phosphorylation of ASR3 at threonine 189
      via MPK4, a mitogen-activated protein kinase that negatively regulates PTI
      responses downstream of multiple MAMP receptors. ASR3 possesses transcriptional
      repressor activity via its ERF-associated amphiphilic repression motifs and
      negatively regulates a large subset of flg22-induced genes. Phosphorylation of
      ASR3 by MPK4 enhances its DNA binding activity to suppress gene expression.
      Importantly, the asr3 mutant shows enhanced disease resistance to virulent
      bacterial pathogen infection, whereas transgenic plants overexpressing the wild
      type or phospho-mimetic form of ASR3 exhibit compromised PTI responses. Our
      studies reveal a function of the trihelix transcription factors in plant innate
      immunity and provide evidence that ASR3 functions as a transcriptional repressor
      regulated by MAMP-activated MPK4 to fine-tune plant immune gene expression. 

PMID- 25770112
TI  - Understanding support workers' competence development in working with parents
      with intellectual disability.
AB  - Training for support workers who work with parents with intellectual disability
      can be aided by understanding how they perceive the training process and their
      competence development. This study explored the perceptions of competence
      development and the training process in Swedish support workers trained in the
      evidence-informed programme 'Parenting Young Children' (PYC). Training included a
      workshop, monthly peer support groups and access to a programme manual. Five
      focus groups discussed experiences of the PYC programme and the training they
      received. Twelve support workers completed a competency questionnaire. The
      findings of the current study suggest that perceived skill improved over time.
      Specifically, the findings suggest that peer support is a beneficial training
      follow-up mechanism for knowledge exchange and performance reflection. The main
      issues faced in skill development were transfer of learning and accessing parents
      to work with. These findings also highlight the importance of facilitative
      administration and technical support for managers and agencies. 

PMID- 25770111
TI  - Determining the subcellular location of synthesis and assembly of the cell wall
      polysaccharide (1,3; 1,4)-beta-D-glucan in grasses.
AB  - The current dogma for cell wall polysaccharide biosynthesis is that cellulose
      (and callose) is synthesized at the plasma membrane (PM), whereas matrix phase
      polysaccharides are assembled in the Golgi apparatus. We provide evidence that
      (1,3;1,4)-beta-D-glucan (mixed-linkage glucan [MLG]) does not conform to this
      paradigm. We show in various grass (Poaceae) species that MLG-specific antibody
      labeling is present in the wall but absent over Golgi, suggesting it is assembled
      at the PM. Antibodies to the MLG synthases, cellulose synthase-like F6 (CSLF6)
      and CSLH1, located CSLF6 to the endoplasmic reticulum, Golgi, secretory vesicles,
      and the PM and CSLH1 to the same locations apart from the PM. This pattern was
      recreated upon expression of VENUS-tagged barley (Hordeum vulgare) CSLF6 and
      CSLH1 in Nicotiana benthamiana leaves and, consistent with our biochemical
      analyses of native grass tissues, shown to be catalytically active with CSLF6 and
      CSLH1 in PM-enriched and PM-depleted membrane fractions, respectively. These data
      support a PM location for the synthesis of MLG by CSLF6, the predominant
      enzymatically active isoform. A model is proposed to guide future experimental
      approaches to dissect the molecular mechanism(s) of MLG assembly.

PMID- 25770113
TI  - Methotrexate use and risk of lung disease in psoriasis, psoriatic arthritis, and
      inflammatory bowel disease: systematic literature review and meta-analysis of
      randomised controlled trials.
AB  - OBJECTIVE: To evaluate the relative risk of pulmonary disease among patients with
      psoriasis, psoriatic arthritis, and inflammatory bowel disease treated with
      methotrexate. DATA SOURCES: PubMed, Cochrane central register of controlled
      trials, and Embase to 9 January 2014. STUDY SELECTION: Double blind randomised
      controlled trials of methotrexate versus placebo or active comparator agents in
      adults with psoriatic arthritis, psoriasis, or inflammatory bowel disease.
      Studies with fewer than 50 participants or of less than 12 weeks' duration were
      excluded. DATA SYNTHESIS: Two investigators independently searched both
      databases. All authors reviewed selected studies. We compared relative risk
      differences using the Mantel-Haenszel random effects method to assess total
      respiratory adverse events, infectious respiratory adverse events, non-infectious
      respiratory adverse events, interstitial lung disease, and death. RESULTS: Seven
      studies met our inclusion criteria, six with placebo as the comparator.
      Heterogeneity across the studies was not significant (I(2)=0%), allowing
      combination of trial results. 504 respiratory adverse events were documented in
      1630 participants. Methotrexate was not associated with an increased risk of
      adverse respiratory events (relative risk 1.03, 95% confidence interval 0.90 to
      1.17), respiratory infections (1.02, 0.88 to 1.19), or non-infectious respiratory
      events (1.07, 0.58 to 1.96). No pulmonary deaths occurred. CONCLUSIONS: Findings
      suggested that there was no increased risk of lung disease in methotrexate
      treated patients with non-malignant inflammatory diseases. Given the limitations
      of the study, however, we cannot exclude a small but clinically important risk.

PMID- 25770114
TI  - Drug Interactions With Direct-Acting Antivirals for Hepatitis C: Implications for
      HIV and Transplant Patients.
AB  - OBJECTIVE: Review pharmacokinetics of new direct-acting antivirals (DAAs) for
      hepatitis C (HCV) infection and interactions with concomitant immunosuppressant
      and antiretroviral therapies (ART). DATA SOURCES: MEDLINE (1948-January 2015),
      EMBASE (1964-January 2015), International Pharmaceutical Abstracts (1970-January
      2015), Google, and Google Scholar were searched combining the terms simeprevir,
      sofosbuvir, ledipasvir, daclatasvir, paritaprevir, ABT-450, ombitasvir,
      dasabuvir, pharmacokinetics, drug interaction, drug metabolism, HIV,
      antiretroviral, immunosuppressant, transplant. Articles, conference proceedings,
      abstracts, and product monographs were reviewed. STUDY SELECTION AND DATA
      EXTRACTION: Literature on pharmacokinetic or pharmacodynamic interactions with
      DAAs and immunosuppressants or ART was considered for inclusion. Pertinent
      information was extracted and summarized in the review. In the absence of data,
      pharmacokinetic and pharmacodynamic principles were used to predict the
      likelihood of interactions. DATA SYNTHESIS: DAA pharmacokinetics are reviewed and
      drug interaction data are presented with provision of management strategies.
      Fixed-dose combination paritaprevir/ritonavir/ombitasvir plus dasabuvir is most
      susceptible to drug interactions with immunosuppressants and ART mainly due to
      the influence of ritonavir on multiple enzymes. Simeprevir is also prone to drug
      interactions because of cytochrome P450(CYP) 3A4, CYP1A2, P-glycoprotein, and
      OATP1 involvement and is not recommended for use in combination with several HIV
      antiretrovirals (ARVs). Close therapeutic drug monitoring of calcineurin
      inhibitors is required with concomitant simeprevir. Few clinically significant
      interactions are expected with sofosbuvir or ledipasvir. Limited data suggest
      that daclatasvir may be coadministered with immunosuppressants but requires dose
      adjustments with certain ARVs. CONCLUSIONS: None of the DAAs are completely free
      of drug interactions. Awareness and management of drug interactions is critical
      to optimize outcomes and minimize adverse effects in these patient populations.

PMID- 25770115
TI  - Combination therapy when metformin is not an option for type 2 diabetes.
AB  - OBJECTIVE: Consensus on combination options for patients with type 2 diabetes
      mellitus (T2DM) unable to use metformin is lacking. This review summarizes data
      describing-non-metformin based combination therapy. DATA SOURCES: PubMed searches
      (January 1990 to August 2014) were conducted with terms for newer drug therapies
      alone and with the term combination; filters were applied for Clinical Trial,
      Meta Analysis, and English language. STUDY SELECTION AND DATA EXTRACTION: Results
      were reviewed for multicenter, randomized controlled trials of non-metformin
      based combination therapy conducted in the past 5 years and specific to the US or
      multinational populations. DATA SYNTHESIS: Although multiple injectable and oral
      agents have been studied in combination with metformin for management of T2DM,
      data are more limited for combinations without metformin. Combinations of
      incretins (injectable glucagon-like peptide-1 receptor agonists or oral
      dipeptidyl peptidase-4 [DPP-4] inhibitors) with a sulfonylurea,
      thiazolidinedione, or insulin are well studied and provide greater glucose
      lowering efficacy than monotherapy. Incretins are associated with a low risk of
      hypoglycemia when used as monotherapy; the dosage of sulfonylurea or insulin
      should be reduced when used in combination. Newer studies are investigating the
      combined use of an oral sodium-glucose cotransporter 2 inhibitor and a DPP-4
      inhibitor. In a recent study, reductions in glycated hemoglobin (A1C) of 1.1% to
      1.2% and reduced weight with no additive risk of hypoglycemia were observed.
      CONCLUSIONS: Selecting the most appropriate combination therapy for patients with
      T2DM requires balancing clinical benefits with the risks, such as weight gain and
      hypoglycemia. Treatment approaches should be individualized for vulnerable
      patient populations for whom metformin is not appropriate.

PMID- 25770116
TI  - A systematic review on tobacco use among civilian populations affected by armed
      conflict.
AB  - OBJECTIVE: To systematically examine evidence on tobacco use among conflict
      affected civilian populations. DATA SOURCES: Primary quantitative and qualitative
      studies published in English up to April 2014. Bibliographic databases searched
      were EMBASE, Global Health, MEDLINE, PsycEXTRA, PsycINFO, Web of Science,
      Cochrane; with the main terms of: (Smoke*, tobacco*, cigarette*, nicotine, beedi,
      bidi, papirosi, dip, chew, snuff, snus, smokeless tobacco) AND (armed-conflict,
      conflict-affected, conflict, war, refugee, internally displaced, forcibly
      displaced, asylum, humanitarian). Grey literature was searched using humanitarian
      databases, websites and search engines. STUDY SELECTION: Studies were
      independently selected by two reviewers, with a study outcome of tobacco use and
      a population of conflict-affected civilian populations such as internally
      displaced persons, refugees, residents in conflict-affected areas, residents and
      returning forcibly displaced populations returning in stabilised and postconflict
      periods. 2863 studies were initially identified. DATA EXTRACTION: Data were
      independently extracted. The Quality Assessment Tool for Quantitative Studies and
      the Critical Appraisal Skills Programme for qualitative studies were used to
      assess study quality. DATA SYNTHESIS: 39 studies met inclusion criteria and
      descriptive analysis was used. Findings were equivocal on the effect of conflict
      on tobacco use. Evidence was clearer on associations between post-traumatic
      stress and other mental disorders with nicotine dependence. However, there were
      too few studies for definitive conclusions. No study examined the effectiveness
      of tobacco-related interventions. The quantitative studies were moderate (N=13)
      or weak (N=22) quality, and qualitative studies were moderate (N=3) or strong
      (N=2). CONCLUSIONS: Some evidence indicates links between conflict and tobacco
      use but substantially more research is required.

PMID- 25770117
TI  - pCMV-vegf165 Intramuscular Gene Transfer is an Effective Method of Treatment for
      Patients With Chronic Lower Limb Ischemia.
AB  - Effective treatment of chronic lower limb ischemia is one of the most challenging
      issues confronting vascular surgeons. There are a number of choices available to
      the vascular surgeon. Open or endovascular revascularization is the treatment of
      choice when applicable. Current pharmacological therapies play an auxiliary role
      and cannot prevent disease progression. Therefore, new methods of treatment are
      needed. We conducted a phase 2b/3 multicenter randomized controlled clinical
      trial of the intramuscular transfer of a plasmid DNA encoding vascular
      endothelial growth factor (VEGF) 165 with cytomegalovirus promotor (CMV) in
      patients with atherosclerotic lower limb ischemia. A total of 100 patients were
      enrolled in the study, that is, 75 patients were randomized into the test group
      and received 2 intramuscular injections of 1.2 mg of pCMV-vegf165, 14 days apart
      together with standard pharmacological treatment. In all, 25 patients were
      randomized into the control group and received standard treatment only. The
      following end points were evaluated within the first 6 months of the study and
      during a 1.5-year additional follow-up period: pain-free walking distance (PWD),
      ankle-brachial index (ABI), and blood flow velocity (BFV). The pCMV-vegf165
      therapy appeared to be significantly more effective than standard treatment. The
      PWD increased in the test group by 110.4%, 167.2%, and 190.8% at 6 months, 1
      year, and 2 years after treatment, respectively. The pCMV-vegf165 intramuscular
      transfer caused a statistically significant increase in ABI and BFV. There were
      no positive results in the control group. Thus, pCMV-vegf165 intramuscular gene
      transfer is an effective method of treatment of moderate to severe claudication
      due to chronic lower limb ischemia. 

PMID- 25770118
TI  - Testosterone replacement attenuates mitochondrial damage in a rat model of
      myocardial infarction.
AB  - Testosterone can affect cardiovascular disease, but its effects on mitochondrial
      dynamics in the post-infarct myocardium remain unclear. To observe the effects of
      testosterone replacement, a rat model of castration-myocardial infarction (MI)
      was established by ligating the left anterior descending coronary artery 2 weeks
      after castration with or without testosterone treatment. Expression of
      mitochondrial fission and fusion proteins was detected by western blot and
      immunofluorescence 14 days after MI. Cardiac function, myocardial inflammatory
      infiltration and fibrosis, cardiomyocyte apoptosis, mitochondrial microstructure,
      and ATP levels were also assessed. Compared with MI rats, castrated rats showed
      aggravated mitochondrial and myocardial insults, including mitochondrial swelling
      and disordered arrangement; loss of cristae, reduced mitochondrial length;
      decreased ATP levels; cardiomyocyte apoptosis; and impaired cardiac function.
      Results of western blotting analyses indicated that castration downregulated
      peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1A) and
      mitofusin 2, but upregulated dynamin-related protein 1. The results were also
      supported by results obtained using immunofluorescence. However, these
      detrimental effects were reversed by testosterone supplementation, which also
      elevated the upstream AMP-activated protein kinase (AMPK) activation of PGC1A.
      Thus, testosterone can protect mitochondria in the post-infarct myocardium,
      partly via the AMPK-PGC1A pathway, thereby decreasing mitochondrial dysfunction
      and cardiomyocyte apoptosis. The effects of testosterone were confirmed by the
      results of ELISA analyses.

PMID- 25770119
TI  - Amino acid motifs in both the major and minor capsid proteins of HPV51 impact
      antigenicity and infectivity.
AB  - Persistent infection with oncogenic human papillomavirus (HPV) is a prerequisite
      for cervical disease development, yet data regarding the host immune response to
      infection at the genotype level are quite limited. We created pseudoviruses
      bearing the major (L1) and minor (L2) capsid proteins and L1 virus-like particles
      representing the reference sequence and a consensus of 34 European sequences of
      HPV51. Despite the formation of similarly sized particles, motifs in the
      reference L1 and L2 genes had a profound impact on the immunogenicity,
      antigenicity and infectivity of these antigens. The antibody status of women
      exhibiting low-grade disease was similar between HPV16 and the consensus HPV51,
      but both demonstrated discrepancies between binding and neutralizing antibody
      responses. These data support the use of pseudoviruses as the preferred target
      antigen in studies of natural HPV infection and the need to consider variation in
      both the L1 and L2 proteins for the appropriate presentation of antibody
      epitopes. 

PMID- 25770120
TI  - Endovascular treatment of intracranial aneurysms using the Pipeline Flex
      embolization device: a case series of 30 consecutive patients.
AB  - BACKGROUND: The Pipeline Flex embolization device has some peculiarities in
      comparison with the previous generation device. Despite recent reports of the
      modified delivery system, its safety is still unknown. OBJECTIVE: To illustrate
      the intraprocedural and periprocedural complication rate with this new device in
      30 consecutive patients. MATERIAL AND METHODS: Clinical, procedural, and
      angiographic data, including aneurysm size and location, device or devices used,
      angiographic and clinical data were analyzed. RESULTS: 30 patients harboring 30
      aneurysms were analyzed. 39 devices were placed properly. Multiple Pipeline
      embolization devices (PEDs) were used in 7 cases. In 28 devices the distal end
      opened fully from the beginning with a complete wall apposition. In the remaining
      11 devices, distal-end opening of the devices was instant but partial, but fully
      opened easily after recapture. Among the 30 procedures, recapture and reposition
      of the Pipeline Flex was performed four times owing to proximal
      migration/malposition of the device during delivery. Four
      intraprocedural/periprocedural complications occurred, of which 2 resulted in
      major complications, with neurologic deficits persisting for longer than 7 days.
      The 30-day morbidity rate was 6.6%, with no deaths. No aneurysm rupture or
      parenchymal hemorrhage was seen. CONCLUSIONS: The Pipeline Flex embolization
      device allows more precise and controlled deployment than the first-generation
      device. The number of devices and the complication rate during the learning curve
      are lower than reported with the first-generation PED. The new delivery system
      and the resheathing maneuvers do not seem to increase the intraprocedural
      complication rate in comparison with the first-generation PED.

PMID- 25770121
TI  - Hepatocyte growth factor and Met in drug discovery.
AB  - Activation of the hepatocyte growth factor (HGF)-Met pathway evokes dynamic
      biological responses that support the morphogenesis, regeneration and survival of
      cells and tissues. A characterization of conditional Met knockout mice indicates
      that the HGF-Met pathway plays important roles in the regeneration, protection
      and homeostasis of cells such as hepatocytes, renal tubular cells and neurons.
      Preclinical studies in disease models have indicated that recombinant HGF protein
      and expression plasmid for HGF are biological drug candidates for the treatment
      of patients with diseases or injuries that involve impaired tissue function. The
      phase-I and phase-I/II clinical trials of the intrathecal administration of HGF
      protein for the treatment of patients with amyotrophic lateral sclerosis and
      spinal cord injury, respectively, are ongoing. Biological actions of HGF that
      promote the dynamic movement, morphogenesis and survival of cells also closely
      participate in invasion-metastasis and resistance to the molecular-targeted drugs
      in tumour cells. Different types of HGF-Met pathway inhibitors are now in
      clinical trials for treatment of malignant tumours. Basic research on HGF and Met
      has lead to drug discoveries in regenerative medicine and tumour biology. 

PMID- 25770122
TI  - Patients, doctors and the good life (for the patient).

PMID- 25770123
TI  - Averting compassion fatigue and burnout. Who should help us conquer our demons?

PMID- 25770124
TI  - The long-term outcome of orthostatic tremor.
AB  - OBJECTIVES: Orthostatic tremor is a rare condition characterised by high
      frequency tremor that appears on standing. Although the essential clinical
      features of orthostatic tremor are well established, little is known about the
      natural progression of the disorder. We report the long-term outcome based on the
      largest multicentre cohort of patients with orthostatic tremor. METHODS: Clinical
      information of 68 patients with clinical and electrophysiological diagnosis of
      orthostatic tremor and a minimum follow-up of 5 years is presented. RESULTS:
      There was a clear female preponderance (76.5%) with a mean age of onset at 54
      years. Median follow-up was 6 years (range 5-25). On diagnosis, 86.8% of patients
      presented with isolated orthostatic tremor and 13.2% had additional neurological
      features. At follow-up, seven patients who initially had isolated orthostatic
      tremor later developed further neurological signs. A total 79.4% of patients
      reported worsening of orthostatic tremor symptoms. These patients had
      significantly longer symptom duration than those without reported worsening
      (median 15.5 vs 10.5 years, respectively; p=0.005). There was no change in
      orthostatic tremor frequency over time. Structural imaging was largely
      unremarkable and dopaminergic neuroimaging (DaTSCAN) was normal in 18/19 cases.
      Pharmacological treatments were disappointing. Two patients were treated
      surgically and showed improvement. CONCLUSIONS: Orthostatic tremor is a
      progressive disorder with increased disability although tremor frequency is
      unchanged over time. In most cases, orthostatic tremor represents an isolated
      syndrome. Drug treatments are unsatisfactory but surgery may hold promise.

PMID- 25770125
TI  - Phospholipid oxidation generates potent anti-inflammatory lipid mediators that
      mimic structurally related pro-resolving eicosanoids by activating Nrf2.
AB  - Exposure of biological membranes to reactive oxygen species creates a complex
      mixture of distinct oxidized phospholipid (OxPL) species, which contribute to the
      development of chronic inflammatory diseases and metabolic disorders. While the
      ability of OxPL to modulate biological processes is increasingly recognized, the
      nature of the biologically active OxPL species and the molecular mechanisms
      underlying their signaling remain largely unknown. We have employed a combination
      of mass spectrometry, synthetic chemistry, and immunobiology approaches to
      characterize the OxPL generated from the abundant phospholipid 1-palmitoyl-2
      arachidonoyl-sn-glycero-3-phosphocholine (PAPC) and investigated their
      bioactivities and signaling pathways in vitro and in vivo. Our study defines
      epoxycyclopentenones as potent anti-inflammatory lipid mediators that mimic the
      signaling of endogenous, pro-resolving prostanoids by activating the
      transcription factor nuclear factor E2-related factor 2 (Nrf2). Using a library
      of OxPL variants, we identified a synthetic OxPL derivative, which alleviated
      endotoxin-induced lung injury and inhibited development of pro-inflammatory T
      helper (Th) 1 cells. These findings provide a molecular basis for the negative
      regulation of inflammation by lipid peroxidation products and propose a novel
      class of highly bioactive compounds for the treatment of inflammatory diseases.

PMID- 25770126
TI  - Brain Functional and Structural Predictors of Language Performance.
AB  - The relation between brain function and behavior on the one hand and the relation
      between structural changes and behavior on the other as well as the link between
      the 2 aspects are core issues in cognitive neuroscience. It is an open question,
      however, whether brain function or brain structure is the better predictor for
      age-specific cognitive performance. Here, in a comprehensive set of analyses, we
      investigated the direct relation between hemodynamic activity in 2 pairs of
      frontal and temporal cortical areas, 2 long-distance white matter fiber tracts
      connecting each pair and sentence comprehension performance of 4 age groups,
      including 3 groups of children between 3 and 10 years as well as young adults. We
      show that the increasing accuracy of processing complex sentences throughout
      development is correlated with the blood-oxygen-level-dependent activation of 2
      core language processing regions in Broca's area and the posterior portion of the
      superior temporal gyrus. Moreover, both accuracy and speed of processing are
      correlated with the maturational status of the arcuate fasciculus, that is, the
      dorsal white matter fiber bundle connecting these 2 regions. The present data
      provide compelling evidence for the view that brain function and white matter
      structure together best predict developing cognitive performance. 

PMID- 25770128
TI  - A psychological intervention for family carers of people with dementia is
      clinically and cost effective at reducing carer depression and anxiety levels
      over 2 years of follow-up.

PMID- 25770127
TI  - A Powerful New Quantitative Genetics Platform, Combining Caenorhabditis elegans
      High-Throughput Fitness Assays with a Large Collection of Recombinant Strains.
AB  - The genetic variants underlying complex traits are often elusive even in powerful
      model organisms such as Caenorhabditis elegans with controlled genetic
      backgrounds and environmental conditions. Two major contributing factors are: (1)
      the lack of statistical power from measuring the phenotypes of small numbers of
      individuals, and (2) the use of phenotyping platforms that do not scale to
      hundreds of individuals and are prone to noisy measurements. Here, we generated a
      new resource of 359 recombinant inbred strains that augments the existing C.
      elegans N2xCB4856 recombinant inbred advanced intercross line population. This
      new strain collection removes variation in the neuropeptide receptor gene npr-1,
      known to have large physiological and behavioral effects on C. elegans and
      mitigates the hybrid strain incompatibility caused by zeel-1 and peel-1, allowing
      for identification of quantitative trait loci that otherwise would have been
      masked by those effects. Additionally, we optimized highly scalable and accurate
      high-throughput assays of fecundity and body size using the COPAS BIOSORT large
      particle nematode sorter. Using these assays, we identified quantitative trait
      loci involved in fecundity and growth under normal growth conditions and after
      exposure to the herbicide paraquat, including independent genetic loci that
      regulate different stages of larval growth. Our results offer a powerful platform
      for the discovery of the genetic variants that control differences in responses
      to drugs, other aqueous compounds, bacterial foods, and pathogenic stresses. 

PMID- 25770129
TI  - Stigma, the medical model and dementia care: Psychological growth in senior
      health professionals through moral and professional integrity.
AB  - Minimal research explores the impact of a career in dementia care on senior
      health professionals. This study sought positive and negative subjective
      interpretations from seven senior health professionals regarding their
      experiences in dementia care. Data from semi-structured interviews were analysed
      using interpretative phenomenological analysis (IPA). One superordinate theme,
      Honouring stigmatised self, overarched four sub-themes: Systemic stigma,
      Invalidated, Self-respect and Moral integrity and Growth Stigma was interpreted
      as systemically entrenched minimisation of aged care and the aged-care workforce,
      including poor remuneration and training. Participants experienced peer
      invalidation particularly when attempting to resolve complex professional and
      moral challenges in dementia care. These often occurred in the context of efforts
      to individualise care, constrained within a medical model. Paradoxically,
      external invalidation motivated a search for redefining 'self' and moral
      integrity. By wisely acknowledging career experience, growthful domains of self
      respect, optimism, humility and innovation defined professional practice and
      personal choices. Implications are discussed.

PMID- 25770131
TI  - Polytobacco Use Among College Students.
AB  - INTRODUCTION: Use of more than one tobacco product among college students is
      increasing in popularity, leading to nicotine addiction and additional health
      risks. The study (1) examined polytobacco use patterns among college students who
      had ever used tobacco; and (2) assessed the sociodemographic and personal factors
      associated with current polytobacco use, compared to current single product use
      and former tobacco use among college students. METHODS: Of 10,000 randomly
      selected college students from a large public university in the Southeast, a
      sample of 1593 students age 18 or older completed an online survey assessing
      tobacco use and attitudes. Ever tobacco users were included in this study (n =
      662, or 41.6% of survey completers). RESULTS: About 15% of ever users reported
      current polytobacco use, and more than 70% of polytobacco users smoked cigars,
      little cigars, or clove cigarettes in combination with one or more products.
      Cigarettes were the most commonly-used product among single users, followed by
      hookah. Males, underclassmen, and students with greater acceptance of cigarette
      use were more likely to be polytobacco users. Race/ethnicity was marginally
      related to polyuse status, with white/non-Hispanics 28% less likely to be
      polytobacco users versus single product users. CONCLUSIONS: Polytobacco users
      were more likely than single users to consume emerging tobacco products, (ie,
      hookah and electronic cigarettes). Males, underclassmen, and racial/ethnic
      minorities were more at risk for polytobacco use. As young people are
      particularly prone to nicotine addiction, there is a need to further investigate
      polytobacco use among college students.

PMID- 25770130
TI  - The thymic cortical epithelium determines the TCR repertoire of IL-17-producing
      gammadeltaT cells.
AB  - The thymus provides a specialized microenvironment in which distinct subsets of
      thymic epithelial cells (TECs) support T-cell development. Here, we describe the
      significance of cortical TECs (cTECs) in T-cell development, using a newly
      established mouse model of cTEC deficiency. The deficiency of mature cTECs caused
      a massive loss of thymic cellularity and impaired the development of alphabetaT
      cells and invariant natural killer T cells. Unexpectedly, the differentiation of
      certain gammadeltaT-cell subpopulations-interleukin-17-producing Vgamma4 and
      Vgamma6 cells-was strongly dysregulated, resulting in the perturbation of
      gammadeltaT-mediated inflammatory responses in peripheral tissues. These findings
      show that cTECs contribute to the shaping of the TCR repertoire, not only of
      "conventional" alphabetaT cells but also of inflammatory "innate" gammadeltaT
      cells.

PMID- 25770132
TI  - The patients associated with TMPRSS3 mutations are good candidates for electric
      acoustic stimulation.
AB  - OBJECTIVES: To clarify the frequency of TMPRSS3 mutations in the hearing loss
      population, genetic analysis was performed, and detailed clinical characteristics
      were collected. Optical intervention for patients with TMPRSS3 mutations was also
      discussed. METHODS: Massively parallel DNA sequencing (MPS) was applied for the
      target exon-sequencing of 63 deafness genes in a population of 1120 Japanese
      hearing loss patients. RESULTS: Hearing loss in 5 patients was found to be caused
      by compound heterozygous TMPRSS3 mutations, and their detailed clinical features
      were collected and analyzed. Typically, all of the patients showed ski slope type
      audiograms and progressive hearing loss. Three of the 5 patients received
      electric acoustic stimulation (EAS), which showed good results. Further, the
      onset age was found to vary, and there were some correlations between genotype
      and phenotype (onset age). CONCLUSIONS: MPS is a powerful tool for the
      identification of rare causative deafness genes, such as TMPRSS3. The present
      clinical characteristics not only confirmed the findings from previous studies
      but also provided clinical evidence that EAS is beneficial for patients
      possessing TMPRSS3 mutations.

PMID- 25770133
TI  - Eosinophilic Mucin Otomastoiditis and Otopolyposis: A Progressive Form of
      Eosinophilic Otitis Media.
AB  - OBJECTIVE: The purpose of this study is to introduce and define a disease entity
      on a continuum of eosinophilic otitis media: eosinophilic mucin otomastoiditis
      and otopolyposis. METHODS: A case of a 66-year-old woman with complicated chronic
      otitis media is reported. A literature review of the National Library of
      Medicine's online database, with a focus on eosinophilic otitis media and
      eosinophilic mucin rhinosinusitis, was performed. RESULTS: The authors report the
      case of a 66-year-old woman with a history of asthma, chronic rhinosinusitis,
      nasal polyposis, and chronic otitis media who presented with allergic middle ear
      mucin and otic polyps. Treatment involved a tympanomastoidectomy with removal of
      otic polyps and steroid therapy. CONCLUSION: Eosinophilic mucin otomastoiditis
      with otopolyposis is a disease entity on a continuum of eosinophilic otitis
      media. This disease process shares similarities with eosinophilic mucin
      rhinosinusitis. Otic polypectomy and steroids are suggested therapeutic measures.

PMID- 25770134
TI  - Ranolazine reduces remodeling of the right ventricle and provoked arrhythmias in
      rats with pulmonary hypertension.
AB  - Pulmonary arterial hypertension (PAH) is a progressive disease that often results
      in right ventricular (RV) failure and death. During disease progression,
      structural and electrical remodeling of the right ventricle impairs pump
      function, creates proarrhythmic substrates, and triggers for arrhythmias.
      Notably, RV failure and lethal arrhythmias are major contributors to cardiac
      death in patients with PAH that are not directly addressed by currently available
      therapies. Ranolazine (RAN) is an antianginal, anti-ischemic drug that has
      cardioprotective effects in experimental and clinical settings of left-sided
      heart dysfunction. RAN also has antiarrhythmic effects due to inhibition of the
      late sodium current in cardiomyocytes. We therefore hypothesized that RAN could
      reduce the maladaptive structural and electrical remodeling of the right
      ventricle and could prevent triggered ventricular arrhythmias in the
      monocrotaline rat model of PAH. Indeed, in both in vivo and ex vivo experimental
      settings, chronic RAN treatment reduced electrical heterogeneity (right
      ventricular-left ventricular action potential duration dispersion), shortened
      heart-rate corrected QT intervals in the right ventricle, and normalized RV
      dysfunction. Chronic RAN treatment also dose-dependently reduced ventricular
      hypertrophy, reduced circulating levels of B-type natriuretic peptide, and
      decreased the expression of fibrotic markers. In addition, the acute
      administration of RAN prevented isoproterenol-induced ventricular
      tachycardia/ventricular fibrillation and subsequent cardiovascular death in rats
      with established PAH. These results support the notion that RAN can improve the
      electrical and functional properties of the right ventricle, highlighting its
      potential benefits in the setting of RV impairment. 

PMID- 25770135
TI  - Synergistic Effects of a GPR119 Agonist with Metformin on Weight Loss in Diet
      Induced Obese Mice.
AB  - G protein-coupled receptor 119 (GPR119) is a G protein-coupled receptor expressed
      predominantly in pancreatic beta-cells and gastrointestinal enteroendocrine
      cells. Metformin is a first-line treatment of type 2 diabetes, with minimal
      weight loss in humans. In this study, we investigated the effects of GSK2041706
      [2-([(1S)-1-(1-[3-(1-methylethyl)-1,2,4-oxadiazol-5-yl]-4-piperidinyl)ethyl]oxy)
      5-[4-(methylsulfonyl)phenyl]pyrazine], a GPR119 agonist, and metformin as
      monotherapy or in combination on body weight in a diet-induced obese (DIO) mouse
      model. Relative to vehicle controls, 14-day treatment with GSK2041706 (30 mg/kg
      b.i.d.) or metformin at 30 and 100 mg/kg b.i.d. alone caused a 7.4%, 3.5%, and
      4.4% (all P < 0.05) weight loss, respectively. The combination of GSK2041706 with
      metformin at 30 or 100 mg/kg resulted in a 9.5% and 16.7% weight loss,
      respectively. The combination of GSK2041706 and metformin at 100 mg/kg caused a
      significantly greater weight loss than the projected additive weight loss of
      11.8%. This body weight effect was predominantly due to a loss of fat. Cumulative
      food intake was reduced by 17.1% with GSK2041706 alone and 6.6% and 8.7% with
      metformin at 30 and 100 mg/kg, respectively. The combination of GSK2041706 with
      metformin caused greater reductions in cumulative food intake (22.2% at 30 mg/kg
      and 37.5% at 100 mg/kg) and higher fed plasma glucagon-like peptide 1 and peptide
      tyrosine tyrosine levels and decreased plasma insulin and glucose-dependent
      insulinotropic polypeptide levels compared with their monotherapy groups. In
      addition, we characterized the effect of GSK2041706 and metformin as monotherapy
      or in combination on neuronal activation in the appetite regulating centers in
      fasted DIO mice. In conclusion, our data demonstrate the beneficial effects of
      combining a GPR119 agonist with metformin in the regulation of body weight in DIO
      mice. 

PMID- 25770136
TI  - Combination of cadmium and high cholesterol levels as a risk factor for heart
      fibrosis.
AB  - The deleterious effects of increased cadmium (Cd) serum levels on the
      cardiovascular system are proven by epidemiological and basic science studies. Cd
      exposure of animals and humans is known to impair myocardial function, possibly
      leading to heart failure. This study aims at investigating the effect of Cd
      treatment on the cardiac system with emphasis on the combined effect of Cd and
      high serum cholesterol levels as an important cardiovascular risk factor.
      Detailed analyses of Cd-induced effects on the heart of ApoE-/- mice fed a high
      fat diet (HFD), ApoE-/- mice fed a normal diet (ND), and C57BL/6J mice fed a ND
      revealed proinflammatory and fibrotic changes in the presence of cellular
      hypertrophy but in the absence of organ hypertrophy. Hypercholesterolemia in ApoE
      /- mice alone and in combination with Cd treatment resulted in significant
      cardiomyocyte cell death. Based on further analyses of heart sections, we
      conclude that severe hypercholesterolemia in combination with ApoE-/- genotype as
      well as Cd treatment results in necrotic cardiomyocyte death. These data were
      supported by in vitro experiments showing a Cd-induced depolarization of the
      mitochondrial membrane and the permeabilization of the plasma membrane arguing
      for the occurrence of Cd-induced necrotic cell death. In summary, we were able to
      show for the first time that the combination of high cholesterol and Cd levels
      increase the risk for heart failure through cardiac fibrosis. This observation
      could in part be explained by the dramatically increased deposition of Cd in the
      hearts of ApoE-/- mice fed a HFD.

PMID- 25770137
TI  - Assessing the Validity of Participant-Derived Compared to Staff-Derived Values to
      Compute a Binge Score.
AB  - AIMS: This study examined the validity of two methods of classifying binge
      drinkers. METHODS: Adult drinkers (n = 166) completed the Alcohol Use
      Questionnaire (AUQ) and a Timeline Followback (TLFB) interview to characterize
      drinking during the past 28 days. Using Townshend and Duka's (2005)
      recommendations, answers on three AUQ items (average drinks per hour, number of
      times drunk within the prior 6 months and percentage of times drunk when
      drinking) were used to derive a binge score that was then used to classify
      drinkers as Binge, Non-Binge and Unclassifiable. Two methods for calculating
      binge scores were compared: (a) Participant-derived, using participants' answers
      on the 3 AUQ items; and (b) Staff-derived, staff used TLFB interview information
      to answer the 3 AUQ items. Additionally, Participant- and Staff-derived
      classifications were used to predict future drinking behaviors assessed by a
      second TLFB interview. RESULTS: Participant- and Staff-derived binge scores had a
      low concordance rate. Staff-derived classifications were better than Participant
      derived classifications at predicting future binge drinking behavior and
      identifying group differences in drinking behavior reported during the second
      TLFB interview (average drinks per hour, number of times drunk within the prior 6
      months, and percentage of times drunk when drinking). CONCLUSIONS: Classifying
      drinkers using staff-guided TLFB interview methods instead of self-reported
      participant generalizations of typical drinking habits better relates to real
      world drinking. Classification schemes that rely on dichotomous categorization of
      drinkers (Binge vs. Non-Binge) may be missing individuals who engage in harmful
      patterns of drinking. A continuous scale or index characterizing problematic
      drinking may be more useful.

PMID- 25770138
TI  - Alcohol dependence and serotonin transporter functional polymorphisms 5-HTTLPR
      and rs25531 in an Italian population.
AB  - AIMS: The role of the serotonin transporter gene (SLC6A4) in alcohol dependence
      (AD) is still unclear. In this paper, we have evaluated the association of the
      SLC6A4 gene polymorphisms 5-HTTLPR and rs25531 in AD and assessed the polymorphic
      patterns both in alcoholics and in healthy people of an Italian population.
      METHODS: Genotyping of the 5-HTTLPR (L/S) and rs25531 (A/G) polymorphisms of the
      SLC6A4 gene was performed on 403 alcoholics outpatients and 427 blood donors.
      RESULTS: Comparing AD and control populations and taking into account statistical
      correction for multiple testing, we found no statistically significant
      differences for 5-HTTLPR (L/S) and rs25531 polymorphisms in terms of either
      genotypes or alleles frequencies. By univariate ANOVA, a statistically
      significant difference was found in the onset of AD: the mean age of onset
      resulted to be of 25.4 years in males in respect to 28.1 in females. In
      particular in males, the early AD onset was different, in a statistically
      significant manner, depending on the presence of at least one S or Lg allele
      (24.6 years) in respect to La homozygotes (27.5 years) (P = 0.03). CONCLUSIONS:
      These findings suggest that genetic factors contribute, together with gender and
      age, to the onset differences in alcohol-dependent phenotypes.

PMID- 25770139
TI  - Reliable Assay of Acid Sphingomyelinase Deficiency with the Mutation Q292K by
      Tandem Mass Spectrometry.

PMID- 25770140
TI  - Considerations for the Utility of the CPIC Guideline for CYP2D6 Genotype and
      Codeine Therapy.

PMID- 25770141
TI  - An unusual case of asymptomatic spontaneous umbilical endometriosis treated with
      skin-sparing excision.
AB  - Spontaneous umbilical endometriosis is a rare extrapelvic manifestation of
      endometriosis. Very few such cases have been previously reported, almost always
      associated with a variety of symptoms, usually during menstruation. We present a
      case of asymptomatic umbilical endometriosis treated with skin-sparing excision.
      Differential diagnoses relevant to the clinician, as well as treatment options,
      are also presented. Surgeons should always consider umbilical endometriosis in
      their diagnostic approach when confronted with atypical umbilical nodules,
      regardless of whether they are symptomatic or not. 

PMID- 25770142
TI  - Perforated diverticulitis sigmoidei after laparoscopic cholecystectomy.
AB  - We present a case of 47-year-old healthy man who underwent an uneventful elective
      laparoscopic cholecystectomy. Despite the postoperative analgesia with non
      steroidal anti-inflammatory drugs (NSAIDs), the patient developed diffuse
      abdominal pain culminating on the second postoperative day when the patient also
      had rebound tenderness. A diagnostic laparoscopy showed diverticular perforation,
      which was treated with laparoscopic lavage and drain. The patient's condition
      continued to deteriorate and the drain output resembled faecal material
      necessitating an emergency sigmoidium resection. The histopathological
      examination confirmed inflammation and perforation in the diverticulosis-bearing
      segment. The use of NSAID can be a reason for perforation, and may be for
      diverticulitis. NSAID should be used with caution in patients with a previous
      history or endoscopic-verified diverticulosis. 

PMID- 25770143
TI  - The cone dysfunction syndromes.
AB  - The cone dysfunction syndromes are a heterogeneous group of inherited,
      predominantly stationary retinal disorders characterised by reduced central
      vision and varying degrees of colour vision abnormalities, nystagmus and
      photophobia. This review details the following conditions: complete and
      incomplete achromatopsia, blue-cone monochromatism, oligocone trichromacy,
      bradyopsia and Bornholm eye disease. We describe the clinical, psychophysical,
      electrophysiological and imaging findings that are characteristic to each
      condition in order to aid their accurate diagnosis, as well as highlight some
      classically held notions about these diseases that have come to be challenged
      over the recent years. The latest data regarding the genetic aetiology and
      pathological changes observed in the cone dysfunction syndromes are discussed,
      and, where relevant, translational avenues of research, including completed and
      anticipated interventional clinical trials, for some of the diseases described
      herein will be presented. Finally, we briefly review the current management of
      these disorders. 

PMID- 25770144
TI  - Effect of intravitreal ranibizumab injections on aqueous humour concentrations of
      vascular endothelial growth factor and pigment epithelium-derived factor in
      patients with myopic choroidal neovascularisation.
AB  - AIMS: To investigate aqueous humour changes in vascular endothelial growth factor
      (VEGF) and pigment epithelium-derived factor (PEDF) levels in patients with
      choroidal neovascularisation (CNV) secondary to pathological myopia (mCNV) before
      and after intravitreal ranibizumab injection (IVR). METHODS: This was a
      prospective, case-control study investigating aqueous levels of VEGF and PEDF in
      eyes with mCNV treated with IVR. RESULTS: Mean VEGF and PEDF levels in the
      aqueous humour of control patients were 25.7+/-4.9 pg/mL and 12.6+/-3.5 ng/mL,
      respectively. Lower levels of both VEGF (19.5+/-5.4 pg/mL) and PEDF (4.7+/-2.2
      ng/mL) were found in patients with mCNV before IVR. After IVR, aqueous VEGF
      levels significantly reduced to 6.5+/-2.7 pg/mL, while PEDF levels significantly
      increased to 35.8+/-11.4 ng/mL. VEGF and PEDF levels significantly correlated
      with each other, and with best-corrected visual acuity and central retinal
      thickness. CONCLUSIONS: The VEGF and PEDF levels in aqueous humour were
      significantly lower in the myopic group than in controls. Moreover, IVR resulted
      in reduced VEGF and increased PEDF levels in patients with mCNV. In mCNV,
      neovascularisation is associated with inappropriate VEGF and PEDF expression. A
      balance between VEGF and PEDF is crucial to prevent CNV development. TRIAL
      REGISTRATION NUMBER: NCT02175940.

PMID- 25770145
TI  - Increased atherosclerosis in P2Y13/apolipoprotein E double-knockout mice:
      contribution of P2Y13 to reverse cholesterol transport.
AB  - AIMS: High-density lipoproteins (HDLs) protect against atherosclerosis mainly due
      to their function in hepatobiliary reverse cholesterol transport (RCT). This is a
      process whereby excess cholesterol from peripheral tissues is transported by HDL
      particles to the liver for further metabolism and biliary excretion. Hepatic
      uptake of HDL holoparticles involves the P2Y13 receptor, independently of the
      selective cholesteryl ester uptake mediated by scavenger receptor class B, type I
      (SR-BI). Accordingly, P2Y13-deficient mice (P2Y13 (-/-)) have impaired RCT. This
      study assessed whether P2Y13 deficiency would affect atherosclerotic development.
      METHODS AND RESULTS: P2Y13 (-/-) mice were crossbred with atherosclerosis-prone
      apoE(-/-) mice. When 15 weeks old, P2Y13 (-/-)/apoE(-/-) mice had more aortic
      sinus lesions than apoE(-/-) mice. Bone marrow transplantation showed that the
      absence of the P2Y13 receptor in blood cells did not lead to significantly
      greater atherosclerotic plaque size formation compared with control apoE(-/-)
      reconstituted animals. Conversely, the absence of the P2Y13 receptor, except in
      blood cells, resulted in lesion sizes similar to that in P2Y13 (-/-)/apoE(-/-)
      reconstituted mice, pointing to a role for non-haematopoietic-derived P2Y13.
      Unexpectedly, P2Y13 (-/-)/apoE(-/-) mice displayed a lower HDL-cholesterol level
      than apoE(-/-) mice, which might be due to greater SR-BI expression in the liver.
      However, P2Y13 deficiency in apoE(-/-) mice was translated into reduced biliary
      and faecal sterol excretion and impaired RCT from macrophage to faeces,
      suggesting that an alteration in hepatobiliary RCT could be solely responsible
      for the greater atherosclerosis observed. CONCLUSION: The P2Y13 receptor protects
      against atherosclerosis, primarily through its role in hepatobiliary RCT.

PMID- 25770146
TI  - Targeted inhibition of ANKRD1 disrupts sarcomeric ERK-GATA4 signal transduction
      and abrogates phenylephrine-induced cardiomyocyte hypertrophy.
AB  - AIMS: Accumulating evidence suggest that sarcomere signalling complexes play a
      pivotal role in cardiomyocyte hypertrophy by communicating stress signals to the
      nucleus to induce gene expression. Ankyrin repeat domain 1 (ANKRD1) is a
      transcriptional regulatory protein that also associates with sarcomeric titin;
      however, the exact role of ANKRD1 in the heart remains to be elucidated. We
      therefore aimed to examine the role of ANKRD1 in cardiomyocyte hypertrophic
      signalling. METHODS AND RESULTS: In neonatal rat ventricular myocytes, we found
      that ANKRD1 is part of a sarcomeric signalling complex that includes ERK1/2 and
      cardiac transcription factor GATA4. Treatment with hypertrophic agonist
      phenylephrine (PE) resulted in phosphorylation of ERK1/2 and GATA4 followed by
      nuclear translocation of the ANKRD1/ERK/GATA4 complex. Knockdown of Ankrd1
      attenuated PE-induced phosphorylation of ERK1/2 and GATA4, inhibited nuclear
      translocation of the ANKRD1 complex, and prevented cardiomyocyte growth. Mice
      lacking Ankrd1 are viable with normal cardiac function. Chronic PE infusion in
      wild-type mice induced significant cardiac hypertrophy with reactivation of the
      cardiac fetal gene program which was completely abrogated in Ankrd1 null mice. In
      contrast, ANKRD1 does not play a role in haemodynamic overload as Ankrd1 null
      mice subjected to transverse aortic constriction developed cardiac hypertrophy
      comparable to wild-type mice. CONCLUSION: Our study reveals a novel role for
      ANKRD1 as a selective regulator of PE-induced signalling whereby ANKRD1 recruits
      and localizes GATA4 and ERK1/2 in a sarcomeric macro-molecular complex to enhance
      GATA4 phosphorylation with subsequent nuclear translocation of the ANKRD1 complex
      to induce hypertrophic gene expression.

PMID- 25770147
TI  - Statin use and survival after colorectal cancer: the importance of comprehensive
      confounder adjustment.
AB  - BACKGROUND: Statins have been associated with moderate reductions in mortality
      among colorectal cancer (CRC) patients, but these studies lacked adjustment for
      some potentially relevant factors associated with statin use. We aimed to provide
      more detailed results on this association from a population-based patient cohort
      study. METHODS: Use of statins and other risk or protective factors were assessed
      in standardized interviews with 2697 patients from southern Germany with a
      diagnosis of incident CRC between 2003 and 2009 (Darmkrebs: Chancen der Verhutung
      durch Screening [DACHS] study). Follow-up included assessment of therapy details,
      recurrence, vital status, and cause of death. Information about molecular
      pathological subtypes of CRC was available for 1209 patients. Cox proportional
      hazard regression models were used to estimate adjusted hazard ratios (HRs) and
      their 95% confidence intervals (CIs). All statistical tests were two-sided.
      RESULTS: Patients were age 68 years on average, 412 used statins (15%), and 769
      died during follow-up (29%). After a median follow-up time of 3.4 years, use of
      statins was not associated with overall (HR = 1.10, 95% CI = 0.85 to 1.41), CRC
      specific (HR = 1.11, 95% CI = 0.82 to 1.50), or recurrence-free survival (HR =
      0.90, 95% CI = 0.63 to 1.27). Analyses in relevant subgroups also showed no
      association of statin use with overall and CRC-specific survival, and no
      associations were observed after stratifying for major pathological subtypes.
      Among stage I and II patients, statin use was associated with better recurrence
      free but not with better CRC-specific survival. CONCLUSIONS: Statin use was not
      associated with reduced mortality among CRC patients. Effects reported in
      previous studies might reflect incomplete control for stage at diagnosis and
      other factors associated with the use of statins.

PMID- 25770149
TI  - Angina may trump ischaemia in predicting stable coronary artery disease outcomes,
      but most cardiovascular events occur in patients without angina or asymptomatic
      ischaemia.

PMID- 25770148
TI  - Supplemental security income and social security disability insurance coverage
      among long-term childhood cancer survivors.
AB  - Supplemental security income (SSI) and social security disability insurance (DI)
      are federal programs that provide disability benefits. We report on SSI/DI
      enrollment in a random sample of adult, long-term survivors of childhood cancer
      (n = 698) vs a comparison group without cancer (n = 210) from the Childhood
      Cancer Survivor Study who completed a health insurance survey. A total of 13.5%
      and 10.0% of survivors had ever been enrolled on SSI or DI, respectively,
      compared with 2.6% and 5.4% of the comparison group. Cranial radiation doses of
      25 Gy or more were associated with a higher risk of current SSI (relative risk
      [RR] = 3.93, 95% confidence interval [CI] = 2.05 to 7.56) and DI (RR = 3.65, 95%
      CI = 1.65 to 8.06) enrollment. Survivors with severe/life-threatening conditions
      were more often enrolled on SSI (RR = 3.77, 95% CI = 2.04 to 6.96) and DI (RR =
      2.73, 95% CI = 1.45 to 5.14) compared with those with mild/moderate or no health
      conditions. Further research is needed on disability-related financial challenges
      after childhood cancer. 

PMID- 25770150
TI  - Although the evidence is not clear, decreases in prostate cancer mortality in
      specific subgroups of men may be due to screening.

PMID- 25770151
TI  - Post-first-line FOLFOX chemotherapy for grade 3 neuroendocrine carcinoma.
AB  - There is no standard for second-line chemotherapy in poorly differentiated grade
      3 neuroendocrine carcinoma (G3-NEC) patients. We analyzed the antitumor efficacy
      of 5-fluorouracil and oxaliplatin (FOLFOX) chemotherapy in this population. A
      single-center retrospective analysis of consecutive G3-NEC patients treated with
      FOLFOX chemotherapy after failure of a cisplatinum-based regimen between December
      2003 and June 2012 was performed. Progression-free survival (PFS), overall
      survival (OS), response rate, and safety were assessed according to RECIST 1.1
      and NCI.CTC v4 criteria. Twenty consecutive patients were included (seven males
      and 13 females; median age 55; range 23-87 years) with a performance status of 0
      1 in 75% of them. Primary location was gastroenteropancreatic in 12, thoracic in
      four, other in two, and unknown in two patients. There were 12 (65%) large-cell
      and 7 (30%) small-cell G3-NEC tumors, and 1 (5%) unknown. All patients had
      distant metastases. Twelve (60%) patients received FOLFOX as second-line
      treatment and 8 (40%) as third-line treatment or later and the median number of
      administered cycles was 6 (range 3-14). The median follow-up was 19 months.
      Median PFS was 4.5 months. Among the 17 evaluable patients, five partial
      responses (29%), six stable diseases (35%), and six progressive diseases (35%)
      were observed. Median OS was 9.9 months. Main Grade 3-4 toxicities were
      neutropenia (35%), thrombopenia (20%), nausea/vomiting (10%), anemia (10%), and
      elevated liver transaminases (10%). Our results indicate that the FOLFOX regimen
      could be considered as a second-line option in poorly differentiated G3-NEC
      patients after cisplatinum-based first-line treatment but warrant further
      confirmation in future larger prospective studies. 

PMID- 25770152
TI  - Integrity of the pheochromocytoma susceptibility TMEM127 gene in patients with
      pediatric malignancies.

PMID- 25770153
TI  - Hydrogen sulfide regulates inward-rectifying K+ channels in conjunction with
      stomatal closure.
AB  - Hydrogen sulfide (H2S) is the third biological gasotransmitter, and in animals,
      it affects many physiological processes by modulating ion channels. H2S has been
      reported to protect plants from oxidative stress in diverse physiological
      responses. H2S closes stomata, but the underlying mechanism remains elusive.
      Here, we report the selective inactivation of current carried by inward
      rectifying K(+) channels of tobacco (Nicotiana tabacum) guard cells and show its
      close parallel with stomatal closure evoked by submicromolar concentrations of
      H2S. Experiments to scavenge H2S suggested an effect that is separable from that
      of abscisic acid, which is associated with water stress. Thus, H2S seems to
      define a unique and unresolved signaling pathway that selectively targets inward
      rectifying K(+) channels.

PMID- 25770155
TI  - Barcoding method speeds single-cell expression profiling.

PMID- 25770154
TI  - The barley powdery mildew candidate secreted effector protein CSEP0105 inhibits
      the chaperone activity of a small heat shock protein.
AB  - Pathogens secrete effector proteins to establish a successful interaction with
      their host. Here, we describe two barley (Hordeum vulgare) powdery mildew
      candidate secreted effector proteins, CSEP0105 and CSEP0162, which contribute to
      pathogen success and appear to be required during or after haustorial formation.
      Silencing of either CSEP using host-induced gene silencing significantly reduced
      the fungal haustorial formation rate. Interestingly, both CSEPs interact with the
      barley small heat shock proteins, Hsp16.9 and Hsp17.5, in a yeast two-hybrid
      assay. Small heat shock proteins are known to stabilize several intracellular
      proteins, including defense-related signaling components, through their chaperone
      activity. CSEP0105 and CSEP0162 localized to the cytosol and the nucleus of
      barley epidermal cells, whereas Hsp16.9 and Hsp17.5 are cytosolic. Intriguingly,
      only those specific CSEPs changed localization and became restricted to the
      cytosol when coexpressed with Hsp16.9 and Hsp17.5, confirming the CSEP-small heat
      shock protein interaction. As predicted, Hsp16.9 showed chaperone activity, as it
      could prevent the aggregation of Escherichia coli proteins during thermal stress.
      Remarkably, CSEP0105 compromised this activity. These data suggest that CSEP0105
      promotes virulence by interfering with the chaperone activity of a barley small
      heat shock protein essential for defense and stress responses.

PMID- 25770157
TI  - A case of infant botulism in a 4-month-old baby.

PMID- 25770156
TI  - Genomic Complexity Profiling Reveals That HORMAD1 Overexpression Contributes to
      Homologous Recombination Deficiency in Triple-Negative Breast Cancers.
AB  - Triple-negative breast cancers (TNBC) are characterized by a wide spectrum of
      genomic alterations, some of which might be caused by defects in DNA repair
      processes such as homologous recombination (HR). Despite this understanding,
      associating particular patterns of genomic instability with response to therapy
      has been challenging. Here, we show that allelic-imbalanced copy-number
      aberrations (AiCNA) are more prevalent in TNBCs that respond to platinum-based
      chemotherapy, thus providing a candidate predictive biomarker for this disease.
      Furthermore, we show that a high level of AiCNA is linked with elevated
      expression of a meiosis-associated gene, HORMAD1. Elevated HORMAD1 expression
      suppresses RAD51-dependent HR and drives the use of alternative forms of DNA
      repair, the generation of AiCNAs, as well as sensitizing cancer cells to HR
      targeting therapies. Our data therefore provide a mechanistic association between
      HORMAD1 expression, a specific pattern of genomic instability, and an association
      with response to platinum-based chemotherapy in TNBC. SIGNIFICANCE: Previous
      studies have shown correlation between mutational "scars" and sensitivity to
      platinums extending beyond associations with BRCA1/2 mutation, but do not
      elucidate the mechanism. Here, a novel allele-specific copy-number
      characterization of genome instability identifies and functionally validates the
      inappropriate expression of the meiotic gene HORMAD1 as a driver of HR deficiency
      in TNBC, acting to induce allelic imbalance and moderate platinum and PARP
      inhibitor sensitivity with implications for the use of such "scars" and
      expression of meiotic genes as predictive biomarkers.

PMID- 25770159
TI  - The management of type 1 and type 2 diabetes in pregnancy.
AB  - Pregestational diabetes is a common medical complication of pregnancy and
      preconception planning is an essential component of care for affected women of
      childbearing age. Once pregnant, structured care in a multidisciplinary team
      setting is necessary to ensure optimal outcomes. Although significant progress
      has been made, these women and their offspring remain to have a significantly
      elevated risk of multiple adverse complications. Structured programmes using
      information technology and enabling access to novel technologies may facilitate
      our goal of ensuring an outcome closer to that of a pregnancy unaffected by
      diabetes.

PMID- 25770158
TI  - Analysis of anonymized pooled urine in nine UK cities: variation in classical
      recreational drug, novel psychoactive substance and anabolic steroid use.
AB  - BACKGROUND: Analysis of anonymous pooled urine samples from street urinals has
      been used to demonstrate time-trends in the detection of classical recreational
      drugs and novel psychoactive substances (NPS). AIM: This study aimed to expand
      this to undertake a geographical trend analysis of classical recreational
      drugs/NPS across UK. METHODS: Samples of anonymous pooled urine were collected
      from street urinals that had been in place for one night in April 2014 in nine
      cities across the UK. Collected samples were then analysed for the presence of
      recreational drugs, NPS anabolic steroids using high-performance liquid
      chromatography coupled to high-resolution accurate mass full-scan mass
      spectrometry and gas chromatography coupled to electron impact ionization mass
      spectrometry operating in selected ion monitoring and full-scan modes. RESULTS:
      Ten classical recreational drugs, nine NPS and four anabolic steroids were
      detected across the nine cities; the range of detection was from 1 in Leeds to 14
      in London. The most common classical drugs were cocaine (9 cities) and 3,4
      methylenedioxy-methamphetamine (8 cities); the most common NPS was 4
      methylmethcathinone (5 cities). In addition there was variation in the detection
      of NPS, with methylhexaneamine detected only in Bristol and London, piperazines
      (3-trifluoromethylphenylpiperazine and 1-benzylpiperazine) and pentedrone only
      detected in Birmingham and the cathinone methylone only detected in London.
      CONCLUSIONS: There is variability in the detection of classical recreational
      drugs, NPS and anabolic steroids across UK, likely reflecting variation in their
      use. This technique can be used to supplement drug use surveys to determine
      geographical and time trends in the use of these substances. This is important to
      ensure appropriate targeting of drug-related interventions.

PMID- 25770160
TI  - How to define cumulative cancer length for selecting candidate for active
      surveillance?

PMID- 25770161
TI  - Genetic variations in the SOCS3 gene in patients with Graves' ophthalmopathy.
AB  - AIMS: To explore the role of the suppressor of cytokine signalling 3 (SOCS3) gene
      in Graves' ophthalmopathy (GO) patients. METHODS: A case-control study was
      conducted in a Chinese Han population by recruiting 114 Graves' disease (GD)
      patients with GO and 156 GD patients without GO. We determined SOCS3 mRNA and
      protein levels in Epstein-Barr virus-transformed lymphoblastoid cell lines (EBV
      LCLs) from peripheral blood mononuclear cells (PBMCs) by quantitative real-time
      (QRT)-PCR analysis and western blot analysis. We also genotyped five single
      nucleotide polymorphisms (SNPs) in the SOCS3 locus (SOCS3 rs12952093, rs4969170,
      rs4969168, rs4969169 and rs2280148) in all 270 GD patients using ligase detection
      reaction and multiplex PCR analyses. QRT-PCR and western blot assays were then
      performed to compare SOCS3 mRNA and protein levels between the rs4969170 AA and
      GG genotype groups from 20 GO patients. RESULTS: Basal SOCS3 mRNA and protein
      expression levels were significantly increased in patients with GO (p<0.05). The
      SOCS3 rs4969170 AA genotype was strongly associated with GO (OR=3.5, 95% CI 1.6
      to 7.5, p=0.001). The AA genotype carriers had significantly higher SOCS3 mRNA
      and protein levels than those with the GG genotype (p<0.05). CONCLUSIONS:
      Patients with GD who carry the AA genotype of the rs4969170 SNP in SOCS3 are more
      susceptible to the development of GO.

PMID- 25770162
TI  - Expression of CD133 in differentiated thyroid cancer of young patients.
AB  - AIMS: CD133 expression in cancer is frequently associated with poor outcome.
      Thyroid carcinomas are rare in childhood and adolescence and are associated with
      a higher risk of recurrence and more metastases than the adult tumours. The aim
      of the study was to assess whether the expression of CD133 in thyroid carcinomas
      of children, adolescents and young adults was correlated with clinical prognostic
      factors. METHODS: Tissue microarrays were constructed with 235 tumours coming
      from 208 young adults with a median age of 28 years and 27 children with a median
      age of 13 years. An immunohistochemical study was performed with anti-CD133
      antibody. CD133 expression was evaluated, using a semiquantitative score based on
      the percentage of positive cells. The mutation status of tumours was evaluated by
      reverse transcriptase PCR. Three cell lines were used to confirm CD133 expression
      by western blot. RESULTS: CD133 expression was found in 43% of adult and 37% of
      child tumours and was confirmed by western blot in cell lines. In young adults,
      the expression of CD133 was significantly more frequent in patients with tumours
      >3 cm (p=0.04) and in patients with lymph node metastases (p=0.02). The
      expression of CD133 was more frequent in patients in whom the tumour presented a
      BRAF mutation (p=0.03). CONCLUSIONS: CD133 expression is correlated with tumour
      size, lymph nodes metastases and BRAF mutations in young adults. The presence of
      these cancer stem cells could offer new therapeutic alternatives for aggressive
      thyroid cancers.

PMID- 25770163
TI  - Association between the ulcerative colitis endoscopic index of severity (UCEIS)
      and outcomes in acute severe ulcerative colitis.
AB  - BACKGROUND: The Ulcerative Colitis Endoscopic Index of Severity (UCEIS) accounts
      for 86% of the variance between observers in the overall assessment of endoscopic
      severity, but has not been correlated with outcomes. METHODS: Consecutive cases
      of acute severe colitis (ASC) defined by Truelove and Witts (TW) criteria were
      retrospectively evaluated. Demographic details, number of TW criteria, prior
      medical therapy, UCEIS and inpatient medical therapy were recorded. Pre-specified
      (adverse) endpoints included rescue therapy, colectomy and readmission. RESULTS:
      Eighty-nine patients, 48 (54%) male, mean age 38 years, all received intravenous
      hydrocortisone 400mg/d (median 5 days [range 1-11]). Median follow-up was 14
      months (2-33). Forty-eight (54%) were diagnosed the year prior to or at the time
      of admission. Thirty-six (40%) required rescue therapy (infliximab 25/36,
      ciclosporin 12/36, one receiving both). Twenty-one (24%) underwent colectomy on
      the index admission (9/21) or during follow-up (12/21). Median UCEIS score
      (possible range 0-8) was 5 (3-8). UCEIS was higher in patients requiring rescue
      therapy or colectomy (median score 6 [range 4-8] versus 5/8 [3-8], both p <
      0.005). For UCEIS >=5, 27/54 (50%) required rescue therapy, compared with 9/33
      (27%) for UCEIS <=4 (p = 0.037). When UCEIS was >=5, 18/54 (33%) came to
      colectomy during follow-up, compared with 3/33 (9%) with UCEIS <=4. Of 14
      patients with UCEIS 7 or 8, 11/14 needed rescue therapy and 13/14 met any adverse
      endpoint. CONCLUSION: Endoscopic severity is associated with a worse outcome in
      ASC. When the UCEIS is >=7 on admission, almost all patients will need treatment
      with infliximab or ciclosporin beyond steroids. This may mark a threshold for an
      early decision to use infliximab or ciclosporin.

PMID- 25770165
TI  - Ulcerative colitis flare with a sweet ending.

PMID- 25770164
TI  - Managing pregnant patients with inflammatory bowel disease: a difficult
      compromise.

PMID- 25770166
TI  - Plasma exchange in antineutrophil cytoplasmic antibody-associated vasculitis--a
      25-year perspective.
AB  - Demonstration of a pathogenic role for antineutrophil cytoplasmic antibodies
      (ANCA) underlies the scientific rationale for plasma exchange (PLEX) in the
      treatment of ANCA-associated vasculitis (AAV). Most clinical evidence of efficacy
      concerns the use of PLEX for the recovery of renal function in severe nephritis,
      when used in conjunction with immunosuppressive drug therapy. The development of
      PLEX for this indication, the strength of the clinical trial evidence supporting
      its use, its roles in other AAV indications and ongoing research are discussed. 

PMID- 25770167
TI  - More than a kidney disease: a patient-centred approach to improving care in
      autosomal dominant polycystic kidney disease.

PMID- 25770168
TI  - Altered monocyte expression and expansion of non-classical monocyte subset in IgA
      nephropathy patients.
AB  - BACKGROUND: The main defect of immunoglobulin A nephropathy (IgAN) lies within
      the immune system and in peripheral blood mononuclear cells rather than in the
      kidney. Previously, we found an altered gene expression in monocytes compared
      with B and T cells isolated from IgAN patients; thus, our aim here has been to
      study this subset at a genome-wide and functional level. METHODS: A total of 39
      IgAN patients and 37 healthy blood donors (HBDs) were included in this study, and
      microarray technology was used to evaluate global gene expression differences in
      monocytes isolated from IgAN patients and HBDs. Aberrantly expressed genes and
      pathways were then validated on an independent set of IgAN patients with RT-PCR
      western blot and flow cytometric analysis. RESULTS: Gene expression differences
      in monocytes from IgAN patients and HBDs primarily involved apoptosis signalling,
      mitochondrial dysfunction, tnfr2/1 and death receptor signalling. Both the
      extrinsic and intrinsic apoptotic pathways seem to be implicated; in particular,
      the protein levels of NDUFS3 and TNFRSF1A were upregulated thus confirming the
      altered mitochondrial and death receptor homeostasis. Furthermore, the basal
      intracellular protein levels of TNF in monocytes were lower in IgAN patients
      compared with HBDs. We validated at protein level an enhanced apoptotic phenotype
      and a different subset distribution in monocytes from IgAN patients. We found
      that the non-classical monocyte subset (CD14(+)CD16(+)) was significantly
      expanded in all IgAN patients tested even though the total monocyte count
      remained unchanged. CONCLUSIONS: Our findings demonstrate, for the first time, an
      aberrant modulation of the mitochondrial respiratory system in monocytes isolated
      from IgAN patients. Furthermore, the aberrant expansion of the (CD14(+)CD16(+))
      subset could explain the enhanced apoptotic phenotype seen in these cells thus
      revealing their potential role in the pathogenesis of IgAN.

PMID- 25770169
TI  - The challenge of controlling phosphorus in chronic kidney disease.
AB  - The pathogenesis and management of chronic kidney disease-mineral bone disorders
      (CKD-MBD) has experienced major changes, but the control of serum phosphorus at
      all stages of CKD still seems to be a key factor to improve clinical outcomes.
      High serum phosphorus is the most important uremia-related, non-traditional risk
      factor associated with vascular calcification in CKD patients and in the general
      population. Phosphorus may also be one of the key elements linking vascular
      calcification with low bone turnover. The main hormones and factors that
      contribute to the kidney regulation of phosphorus and calcium include parathyroid
      hormone, FGF-23, klotho and 1,25-dihydroxyvitamin D (1,25(OH)2D). Serum
      phosphorus did not start rising until CKD 3b in contrast with the earlier changes
      observed with fibroblast growth factor-23 (FGF-23), Klotho, calcitriol and
      parathyroid hormone (PTH). Despite FGF-23 and PTH having synergic effects
      regarding phosphorus removal, they have opposite effects on 1,25(OH)2D3. At the
      same stages of CKD in which phosphorus retention appears to occur, calcium
      retention also occurs. As phosphorus accumulation is associated with poor
      outcomes, an important question without a clear answer is at which level-range
      should serum phosphorus be maintained at different stages of CKD to improve
      clinical outcomes. There are four main strategies to manage phosphate
      homeostasis; phosphorus dietary intake, administration of phosphate binder
      agents, effective control of hyperparathyroidism and to ensure in the CKD 5D
      setting, an adequate scheme of dialysis. Despite all the available strategies,
      and the introduction of new phosphate binder agents in the market, controlling
      serum phosphorus remains challenging, and hyperphosphatemia continues to be
      extremely common in CKD 5 patients. Furthermore, despite phosphate binding agents
      having proved to be effective in reducing serum phosphorus, their ultimate
      effects on clinical outcomes remain controversial. Thus, we still need well
      designed, large-scale, placebo-controlled studies to definitively prove that the
      reduction of serum phosphorus by phosphate binders improves clinical outcomes.

PMID- 25770170
TI  - Editorial commentary: fighting ebola and advancing knowledge on the front lines
      in a capital city.

PMID- 25770171
TI  - Outbreak of trichinellosis due to wild boar meat and evaluation of the
      effectiveness of post exposure prophylaxis, Germany, 2013.
AB  - BACKGROUND: Food safety authorities discovered that wild boar meat products
      contaminated with Trichinella spiralis had entered the food chain in Germany in
      March 2013. Public health authorities issued guidelines for health professionals
      including post-exposure prophylaxis (PEP) using mebendazole and advised the
      public to seek medical advice if exposed. Our objective was to identify factors
      associated with the development of trichinellosis and to evaluate post exposure
      prophylaxis. METHODS: Persons who reported to local public health departments as
      exposed were interviewed concerning exposure, symptoms, and medication. Serum
      samples were tested by an in-house Trichinella-specific enzyme-linked
      innunosorbent assay. Cases were defined as persons presenting with myalgia and/or
      periorbital edema and Trichinella-specific immunoglobulin M and immunoglobulin G
      antibodies after exposure to implicated products. RESULTS: Of 101 persons
      interviewed, 71 were exposed and serologically tested. Antibodies were detected
      in 21/71 (30%) and 14/71 (20%) met the case definition. Attack rates were
      positively correlated to the amount of implicated product consumed. Among n = 37
      persons who received anthelmintics as PEP, 6 persons developed trichinellosis.
      These cases exclusively occurred among persons starting PEP 6 days or later post
      exposure. Exposure to implicated products and delaying PEP were also
      significantly associated with developing trichinellosis (P < .01) in a
      multivariable analysis. CONCLUSIONS: Concerted efforts by food safety and public
      health authorities lead to timely outbreak control and facilitated the provision
      of early PEP. PEP appears to be effective in preventing trichinellosis when given
      early, preferably within 6 days. We therefore recommend initiating PEP without
      delay in similar settings and encourage public health professionals to fast-track
      this intervention.

PMID- 25770172
TI  - Clinical predictors of mortality in patients with Ebola virus disease.
AB  - In an observational cohort study including 89 Ebola patients, predictive factors
      of death were analyzed. The crude mortality rate was 43.8%. Myalgia (adjusted
      odds ratio [OR], 4.04; P = .02), hemorrrhage (adjusted OR, 3.5; P = .02), and
      difficulty breathing (adjusted OR, 5.75; P = .01) were independently associated
      with death. 

PMID- 25770173
TI  - Treatment to Prevent HIV Transmission in Serodiscordant Couples in Henan, China,
      2006 to 2012.
AB  - BACKGROUND: Antiretroviral therapy (ART) administered in clinical trial settings
      virtually eliminates the sexual transmission of human immunodeficiency virus
      (HIV) in serodiscordant couples, but effectiveness of treatment as prevention in
      the community is debated. Conflicting results from previous analyses in a Chinese
      cohort underscore the importance of determining effectiveness of ART delivered in
      resource limited settings. METHODS: All available years of data (2006-2012) from
      local disease control records of HIV patients and their seronegative spouses in
      Henan Province, China, were analyzed using marginal structural Cox models to
      estimate the effect of ART in the initially infected partner his or her partner's
      HIV seroconversion risk. RESULTS: We observed 157 seroconversion events in 4916
      serosdiscordant couples, for an incidence rate of 0.59 cases per 100 person-years
      (PY) (95% confidence interval [CI], .51-.70). Of these, 84 occurred after the
      index partner had initiated ART (0.43/100PY; 95% CI, .35-.53) and 73, whereas
      index partners were untreated (5.87/100 PY; 95% CI, 4.65-7.42). In a marginal
      structural Cox model weighted for confounding and censoring, the hazard ratio
      (HR) for HIV transmission was 0.52 (95% CI, .34-.82). ART efficacy varied
      significantly by time period; least effective in the early phase from 2006 to
      2008 (HR, 0.68; 95% CI, .34-1.36) but far more protective from 2009 onward (HR,
      0.33; 95% CI, .20-.55). CONCLUSIONS: ART can provide HIV-infected persons in
      resource-limited setting substantial protection against sexual transmission.
      Effectiveness in the Henan cohort appears to have increased over time, suggesting
      that quality of care and service infrastructure may be integral to successful use
      of treatment for prevention.

PMID- 25770174
TI  - Is nutritional vitamin D supplementation beneficial in dialysis patients?

PMID- 25770175
TI  - Vascular calcification in patients with nondialysis CKD over 3 years.
AB  - BACKGROUND AND OBJECTIVES: Vascular calcification (VC) is common in CKD, but
      little is known about its prognostic effect on patients with nondialysis CKD. The
      prevalence of VC and its ability to predict death, time to hospitalization, and
      renal progression were assessed. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS:
      The Study of Mineral and Bone Disorders in CKD in Spain is a prospective,
      observational, 3-year follow-up study of 742 patients with nondialysis CKD stages
      3-5 from 39 centers in Spain from April to May 2009. VC was assessed using
      Adragao (AS; x-ray pelvis and hands) and Kauppila (KS; x-ray lateral lumbar
      spine) scores from 572 and 568 patients, respectively. The primary end point was
      death. Secondary outcomes were hospital admissions and appearance of a combined
      renal end point (beginning of dialysis or drop >30% in eGFR). Factors related to
      VC were assessed by logistic regression analysis. Survival analysis was assessed
      by Cox proportional models. RESULTS: VC was present in 79% of patients and
      prominent in 47% (AS>=3 or KS>6). Age (odds ratio [OR], 1.05; 95% confidence
      interval [95% CI], 1.02 to 1.07; P<0.001), phosphorous (OR, 1.68; 95% CI, 1.28 to
      2.20; P<0.001), and diabetes (OR, 2.11; 95% CI, 1.32 to 3.35; P=0.002) were
      independently related to AS>=3. After a median follow-up of 35 months
      (interquartile range=17-36), there were 70 deaths (10%). After multivariate
      adjustment for age, smoking, diabetes, comorbidity, renal function, and level of
      phosphorous, AS>=3 but not KS>6 was independently associated with all-cause
      (hazard ratio [HR], 2.07; 95% CI, 1.07 to 4.01; P=0.03) and cardiovascular (HR,
      3.46; 95% CI, 1.27 to 9.45; P=0.02) mortality as well as a shorter
      hospitalization event-free period (HR, 1.14; 95% CI, 1.06 to 1.22; P<0.001). VC
      did not predict renal progression. CONCLUSIONS: VC is highly prevalent in
      patients with CKD. VC assessment using AS independently predicts death and time
      to hospitalization. Therefore, it could be a useful index to identify patients
      with CKD at high risk of death and morbidity as previously reported in patients
      on dialysis.

PMID- 25770177
TI  - Vascular calcification in predialysis CKD: common and deadly.

PMID- 25770176
TI  - Nutritional vitamin D supplementation in dialysis: a randomized trial.
AB  - BACKGROUND AND OBJECTIVES: Vitamin D (25-hydroxyvitamin D; 25[OH]D) deficiency is
      common in patients initiating long-term hemodialysis, but the safety and efficacy
      of nutritional vitamin D supplementation in this population remain uncertain.
      DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: This randomized, placebo
      controlled, parallel-group multicenter trial compared two doses of ergocalciferol
      with placebo between October 2009 and March 2013. Hemodialysis patients (n=105)
      with 25(OH)D levels <=32 ng/ml from 32 centers in the Northeast United States
      were randomly assigned to oral ergocalciferol, 50,000 IU weekly (n=36) or monthly
      (n=33), or placebo (n=36) for a 12-week treatment period. The primary endpoint
      was the achievement of vitamin D sufficiency (25[OH]D >32 ng/ml) at the end of
      the 12-week treatment period. Survival was assessed through 1 year. RESULTS:
      Baseline characteristics were similar across all arms, with overall mean+/-SD
      25(OH)D levels of 21.9+/-6.9 ng/ml. At 12 weeks, vitamin D sufficiency (25[OH]D
      >32 ng/ml) was achieved in 91% (weekly), 66% (monthly), and 35% (placebo)
      (P<0.001). Mean 25(OH)D was significantly higher in both the weekly (49.8+/-2.3
      ng/ml; P<0.001) and monthly (38.3+/-2.4 ng/ml; P=0.001) arms compared with
      placebo (27.4+/-2.3 ng/ml). Calcium, phosphate, parathyroid hormone levels, and
      active vitamin D treatment did not differ between groups. All-cause and cause
      specific hospitalizations and adverse events were similar between groups during
      the intervention period. Lower all-cause mortality among ergocalciferol-treated
      participants was not statistically significant (hazard ratio, 0.28; 95%
      confidence interval, 0.07 to 1.19). CONCLUSIONS: Oral ergocalciferol can increase
      25(OH)D levels in incident hemodialysis patients without significant alterations
      in blood calcium, phosphate, or parathyroid hormone during a 12-week period.

PMID- 25770178
TI  - Kinetic profiling of in vivo lung cellular inflammatory responses to mechanical
      ventilation.
AB  - Mechanical ventilation, through overdistension of the lung, induces substantial
      inflammation that is thought to increase mortality among critically ill patients.
      The mechanotransduction processes involved in converting lung distension into
      inflammation during this ventilator-induced lung injury (VILI) remain unclear,
      although many cell types have been shown to be involved in its pathogenesis. This
      study aimed to identify the profile of in vivo lung cellular activation that
      occurs during the initiation of VILI. This was achieved using a flow cytometry
      based method to quantify the phosphorylation of several markers (p38, ERK1/2,
      MAPK-activated protein kinase 2, and NF-kappaB) of inflammatory pathway
      activation within individual cell types. Anesthetized C57BL/6 mice were
      ventilated with low (7 ml/kg), intermediate (30 ml/kg), or high (40 ml/kg) tidal
      volumes for 1, 5, or 15 min followed by immediate fixing and processing of the
      lungs. Surprisingly, the pulmonary endothelium was the cell type most responsive
      to in vivo high-tidal-volume ventilation, demonstrating activation within just 1
      min, followed by the alveolar epithelium. Alveolar macrophages were the slowest
      to respond, although they still demonstrated activation within 5 min. This order
      of activation was specific to VILI, since intratracheal lipopolysaccharide
      induced a very different pattern. These results suggest that alveolar macrophages
      may become activated via a secondary mechanism that occurs subsequent to
      activation of the parenchyma and that the lung cellular activation mechanism may
      be different between VILI and lipopolysaccharide. Our data also demonstrate that
      even very short periods of high stretch can promote inflammatory activation, and,
      importantly, this injury may be immediately manifested within the pulmonary
      vasculature. 

PMID- 25770180
TI  - Association between early airway damage-associated molecular patterns and
      subsequent bacterial infection in patients with inhalational and burn injury.
AB  - Bacterial infection is a major cause of morbidity affecting outcome following
      burn and inhalation injury. While experimental burn and inhalation injury animal
      models have suggested that mediators of cell damage and inflammation increase the
      risk of infection, few studies have been done on humans. This is a prospective,
      observational study of patients admitted to the North Carolina Jaycee Burn Center
      at the University of North Carolina who were intubated and on mechanical
      ventilation for treatment of burn and inhalational injury. Subjects were enrolled
      over a 2-yr period and followed till discharge or death. Serial bronchial
      washings from clinically indicated bronchoscopies were collected and analyzed for
      markers of tissue injury and inflammation. These include damage-associated
      molecular patterns (DAMPs) such as hyaluronic acid (HA), double-stranded DNA
      (dsDNA), heat-shock protein 70 (HSP-70), and high-mobility group protein B-1
      (HMGB-1). The study population was comprised of 72 patients who had bacterial
      cultures obtained for clinical indications. Elevated HA, dsDNA, and IL-10 levels
      in bronchial washings obtained early (the first 72 h after injury) were
      significantly associated with positive bacterial respiratory cultures obtained
      during the first 14 days postinjury. Independent of initial inhalation injury
      severity and extent of surface burn, elevated levels of HA dsDNA and IL-10 in the
      central airways obtained early after injury are associated with subsequent
      positive bacterial respiratory cultures in patients intubated after acute
      burn/inhalation injury. 

PMID- 25770179
TI  - Utility of large-animal models of BPD: chronically ventilated preterm lambs.
AB  - This paper is focused on unique insights provided by the preterm lamb
      physiological model of bronchopulmonary dysplasia (BPD). Connections are also
      made to insights provided by the former preterm baboon model of BPD, as well as
      to rodent models of lung injury to the immature, postnatal lung. The preterm lamb
      and baboon models recapitulate the clinical setting of preterm birth and
      respiratory failure that require prolonged ventilation support for days or weeks
      with oxygen-rich gas. An advantage of the preterm lamb model is the large size of
      preterm lambs, which facilitates physiological studies for days or weeks during
      the evolution of neonatal chronic lung disease (CLD). To this advantage is linked
      an integrated array of morphological, biochemical, and molecular analyses that
      are identifying the role of individual genes in the pathogenesis of neonatal CLD.
      Results indicate that the mode of ventilation, invasive mechanical ventilation
      vs. less invasive high-frequency nasal ventilation, is related to outcomes. Our
      approach also includes pharmacological interventions that test causality of
      specific molecular players, such as vitamin A supplementation in the pathogenesis
      of neonatal CLD. The new insights that are being gained from our preterm lamb
      model may have important translational implications about the pathogenesis and
      treatment of BPD in preterm human infants. 

PMID- 25770182
TI  - Carbon monoxide negatively regulates NLRP3 inflammasome activation in
      macrophages.
AB  - Inflammasomes are cytosolic protein complexes that promote the cleavage of
      caspase-1, which leads to the maturation and secretion of proinflammatory
      cytokines, including interleukin-1beta (IL-1beta) and IL-18. Among the known
      inflammasomes, the nucleotide-binding domain, leucine-rich-containing family,
      pyrin domain-containing-3 (NLRP3)-dependent inflammasome is critically involved
      in the pathogenesis of various acute or chronic inflammatory diseases. Carbon
      monoxide (CO), a gaseous molecule physiologically produced in cells and tissues
      during heme catabolism, can act as an anti-inflammatory molecule and a potent
      negative regulator of Toll-like receptor signaling pathways. To date, the role of
      CO in inflammasome-mediated immune responses has not been fully investigated.
      Here, we demonstrated that CO inhibited caspase-1 activation and the secretion of
      IL-1beta and IL-18 in response to lipopolysaccharide (LPS) and ATP treatment in
      bone marrow-derived macrophages. CO also inhibited IL-18 secretion in response to
      LPS and nigericin treatment, another NLRP3 inflammasome activation model. In
      contrast, CO did not suppress IL-18 secretion in response to LPS and poly(dA:dT),
      an absent in melanoma 2 (AIM2)-mediated inflammasome model. LPS and ATP
      stimulation induced the formation of complexes between NLRP3 and apoptosis
      associated speck-like protein, or NLRP3 and caspase-1. CO treatment inhibited
      these molecular interactions that were induced by LPS and ATP. Furthermore, CO
      inhibited mitochondrial ROS generation and the decrease of mitochondrial membrane
      potential induced by LPS and ATP in macrophages. We also observed that the
      inhibitory effect of CO on the translocation of mitochondrial DNA into the
      cytosol was associated with suppression of cytokine secretion. Our results
      suggest that CO negatively regulates NLRP3 inflammasome activation by preventing
      mitochondrial dysfunction. 

PMID- 25770181
TI  - Proresolving actions of a new resolvin D1 analog mimetic qualifies as an
      immunoresolvent.
AB  - Resolution of inflammation is an active process driven by several new families of
      endogenous lipid mediators collectively coined specialized proresolving mediators
      (SPM). Here, we report a synthetic analog of resolvin D1 (RvD1) and aspirin
      triggered RvD1, benzo-diacetylenic-17R-RvD1-methyl ester (BDA-RvD1), which was
      prepared using fewer steps than required for total organic synthesis of natural
      SPM. BDA-RvD1 was resistant to further metabolism by human recombinant 15
      prostaglandin dehydrogenase, a major inactivation pathway for RvD1. In ischemia
      reperfusion-initiated second organ injury, BDA-RvD1 intravenously (1 MUg) reduced
      neutrophil infiltration into the lungs by 58 +/- 9% and was significantly more
      potent than native RvD1. BDA-RvD1 at 100 ng/mouse also shortened the resolution
      interval, Ri, of Escherichia coli peritonitis with a similar potency as RvD1, by
      ~57%, from Ri 10.5 h to 4.5 h. With isolated human phagocytes, BDA-RvD1 at
      picomolar concentrations (10(-12) M) stimulated phagocytosis of zymosan A
      particles. BDA-RvD1 activated human recombinant G protein-coupled receptor
      32/DRV1, an RvD1 receptor, in a dose-dependent manner. These results indicate
      that, both in vivo in mice and with isolated human cells, BDA-RvD1 shares
      defining proresolving actions of RvD1, including inhibiting leukocyte
      infiltration and stimulating phagocytosis. Moreover, they provide evidence for a
      new analog mimetic and example of an immunoresolvent, namely an agent that
      stimulates active resolution of inflammation, for a potential new therapeutic
      class.

PMID- 25770183
TI  - Bazooka/PAR3 is dispensable for polarity in Drosophila follicular epithelial
      cells.
AB  - Apico-basal polarity is the defining characteristic of epithelial cells. In
      Drosophila, apical membrane identity is established and regulated through
      interactions between the highly conserved Par complex (Bazooka/Par3, atypical
      protein kinase C and Par6), and the Crumbs complex (Crumbs, Stardust and PATJ).
      It has been proposed that Bazooka operates at the top of a genetic hierarchy in
      the establishment and maintenance of apico-basal polarity. However, there is
      still ambiguity over the correct sequence of events and cross-talk with other
      pathways during this process. In this study, we reassess this issue by comparing
      the phenotypes of the commonly used baz(4) and baz(815-8) alleles with those of
      the so far uncharacterized baz(XR11) and baz(EH747) null alleles in different
      Drosophila epithelia. While all these baz alleles display identical phenotypes
      during embryonic epithelial development, we observe strong discrepancies in the
      severity and penetrance of polarity defects in the follicular epithelium:
      polarity is mostly normal in baz(EH747) and baz(XR11) while baz(4) and baz(815) (
      8) show loss of polarity, severe multilayering and loss of epithelial integrity
      throughout the clones. Further analysis reveals that the chromosomes carrying the
      baz(4) and baz(815-8) alleles may contain additional mutations that enhance the
      true baz loss-of-function phenotype in the follicular epithelium. This study
      clearly shows that Baz is dispensable for the regulation of polarity in the
      follicular epithelium, and that the requirement for key regulators of cell
      polarity is highly dependent on developmental context and cell type. 

PMID- 25770184
TI  - Aberrant over-expression of TRPM7 ion channels in pancreatic cancer: required for
      cancer cell invasion and implicated in tumor growth and metastasis.
AB  - Our previous studies in zebrafish development have led to identification of the
      novel roles of the transient receptor potential melastatin-subfamily member 7
      (TRPM7) ion channels in human pancreatic cancer. However, the biological
      significance of TRPM7 channels in pancreatic neoplasms was mostly unexplored. In
      this study, we determined the expression levels of TRPM7 in pancreatic tissue
      microarrays and correlated these measurements in pancreatic adenocarcinoma with
      the clinicopathological features. We also investigated the role of TRPM7 channels
      in pancreatic cancer cell invasion using the Matrigel(TM)-coated transwell assay.
      In normal pancreas, TRPM7 is expressed at a discernable level in the ductal cells
      and centroacinar cells and at a relatively high level in the islet endocrine
      cells. In chronic pancreatitis, pre-malignant tissues, and malignant neoplasms,
      there is variable expression of TRPM7. In the majority of pancreatic
      adenocarcinoma specimens examined, TRPM7 is expressed at either moderate-level or
      high-level. Anti-TRPM7 immunoreactivity in pancreatic adenocarcinoma
      significantly correlates with the size and stages of tumors. In human pancreatic
      adenocarcinoma cells in which TRPM7 is highly expressed, short hairpin RNA
      mediated suppression of TRPM7 impairs cell invasion. The results demonstrate that
      TRPM7 channels are over-expressed in a proportion of the pre-malignant lesions
      and malignant tumors of the pancreas, and they are necessary for invasion by
      pancreatic cancer cells. We propose that TRPM7 channels play important roles in
      development and progression of pancreatic neoplasm, and they may be explored as
      clinical biomarkers and targets for its prevention and treatment. 

PMID- 25770186
TI  - Overexpression of KDM4 lysine demethylases disrupts the integrity of the DNA
      mismatch repair pathway.
AB  - The KDM4 family of lysine demethylases consists of five members, KDM4A, -B and -C
      that demethylate H3K9me2/3 and H3K36me2/3 marks, while KDM4D and -E demethylate
      only H3K9me2/3. Recent studies implicated KDM4 proteins in regulating genomic
      instability and carcinogenesis. Here, we describe a previously unrecognized
      pathway by which hyperactivity of KDM4 demethylases promotes genomic instability.
      We show that overexpression of KDM4A-C, but not KDM4D, disrupts MSH6 foci
      formation during S phase by demethylating its binding site, H3K36me3.
      Consequently, we demonstrate that cells overexpressing KDM4 members are defective
      in DNA mismatch repair (MMR), as evident by the instability of four
      microsatellite markers and the remarkable increase in the spontaneous mutations
      frequency at the HPRT locus. Furthermore, we show that the defective MMR in cells
      overexpressing KDM4C is mainly due to the increase in its demethylase activity
      and can be mended by KDM4C downregulation. Altogether, our data suggest that
      cells overexpressing KDM4A-C are defective in DNA MMR and this may contribute to
      genomic instability and tumorigenesis. 

PMID- 25770187
TI  - Isolation of a growth factor stress-induced pancreatic cancer sub-population:
      insight into changes due to micro-environment.
AB  - BACKGROUND: Micro-environment plays a crucial role in determining the phenotypes
      within a tumor. MATERIALS AND METHODS: In order to understand how the micro
      environment affects pancreatic cancer, KLM1 cells were cultured under growth
      factor stress by culturing in foetal bovine serum (FBS)-free and reduced (1%)
      medium over several passages to mimic the core of a solid tumor with low
      vascularisation. RESULTS: Proteomic analysis on these conditioned pancreatic
      cancer cells, called KLM1-S, compared to the parent cell line KLM1 revealed that
      a number of proteins including alpha-enolase, GAPDH, GRP78, HSP60 and STIP-1 were
      dysregulated. Additionally, KLM1-S cells exhibited a 250-fold increase in half
      maximal inhibitory concentration (IC50) over the parent cell line KLM1.
      CONCLUSION: By decreasing their replication rate and levels of intracellular
      reactive oxygen species (ROS), KLM1-S cells are able to resist gemcitabine (GEM).
      The results obtained suggest that in KLM1 different phenotypes are a result of
      cellular plasticity rather than a committed transformation.

PMID- 25770188
TI  - Results, questions, perspectives of a study on human Polyomavirus BK and
      molecular actors in prostate cancer development.
AB  - BACKGROUND: Prostate cancer (PC) is a common tumor in Western countries. Several
      risk factors play significant roles. MYC, BIRC5/survivin, CDC25 and P53 may
      contribute to PC risk. As demonstrated, human Polyomavirus BK (BKV) could affect
      cellular homeostasis contributing to PC pathogenesis. MATERIALS AND METHODS:
      Biological samples were collected from PC patients. Viral RNA was searched using
      quantitative polymerase chain reaction (PCR), whereas a qualitative PCR was
      employed to find particular viral sequences. Proper size amplicons were analyzed.
      Single nucleotide polymorphisms (SNPs) were detected in p53 coding regions by
      means of a specific PCR. C-MYC, BIRC5/survivin and CDC25 gene expression was
      investigated using a Retro Transcriptional Quantitative PCR. RESULTS: Viral DNA
      copy number was higher in cancer tissues taken from Gleason score 9 patients with
      Gleason score 7. Different p53 mutated compared to patients exons were found
      according to tumor advanced stage and a statistical significant correlation was
      found between Gleason score and p53 mutational rate. C-MYC, BIRC5/survivin and
      CDC25 expression was de-regulated according to the literature. CONCLUSION: The
      presence of BKV and its variants in transformed cells does not exclude viral
      pressure in cell immortalization. Expression of other target genes evidenced a
      significant change in their regulation, useful for cancer drug discovery and
      therapies.

PMID- 25770185
TI  - The Rho GTPase Cdc42 regulates hair cell planar polarity and cellular patterning
      in the developing cochlea.
AB  - Hair cells of the organ of Corti (OC) of the cochlea exhibit distinct planar
      polarity, both at the tissue and cellular level. Planar polarity at tissue level
      is manifested as uniform orientation of the hair cell stereociliary bundles. Hair
      cell intrinsic polarity is defined as structural hair bundle asymmetry;
      positioning of the kinocilium/basal body complex at the vertex of the V-shaped
      bundle. Consistent with strong apical polarity, the hair cell apex displays
      prominent actin and microtubule cytoskeletons. The Rho GTPase Cdc42 regulates
      cytoskeletal dynamics and polarization of various cell types, and, thus, serves
      as a candidate regulator of hair cell polarity. We have here induced Cdc42
      inactivation in the late-embryonic OC. We show the role of Cdc42 in the
      establishment of planar polarity of hair cells and in cellular patterning.
      Abnormal planar polarity was displayed as disturbances in hair bundle orientation
      and morphology and in kinocilium/basal body positioning. These defects were
      accompanied by a disorganized cell-surface microtubule network. Atypical protein
      kinase C (aPKC), a putative Cdc42 effector, colocalized with Cdc42 at the hair
      cell apex, and aPKC expression was altered upon Cdc42 depletion. Our data suggest
      that Cdc42 together with aPKC is part of the machinery establishing hair cell
      planar polarity and that Cdc42 acts on polarity through the cell-surface
      microtubule network. The data also suggest that defects in apical polarization
      are influenced by disturbed cellular patterning in the OC. In addition, our data
      demonstrates that Cdc42 is required for stereociliogenesis in the immature
      cochlea. 

PMID- 25770189
TI  - Assessment of the association between micronuclei and the degree of uterine
      lesions and viral load in women with human papillomavirus.
AB  - Infection by human papillomavirus (HPV) is among the main etiologies of cervical
      cancer. The expression of oncogenic viral proteins enables the onset of the
      virus, which can trigger the carcinogenic process. One of the main
      characteristics of this process is the loss of genome stability, including
      chromosome stability. The micronucleus test is a cytogenetic method for the
      detection of genetic alterations that change chromosome behavior during cell
      division resulting in the formation of micronuclei. This method has been applied
      for the early detection of DNA damage in individuals with a greater likelihood of
      developing cancer. The aim of the present study was to assess the association
      between micronucleus expression and the degree of cytological lesions and viral
      load in patients with HPV. The micronucleus analysis revealed differences in the
      number micronuclei found in the groups, which ranged from 0.00067 to 0.00133 in
      the control group and 0.00267 to 0.02433 among patients with HPV. Statistically
      significant differences (p<0.05) were found in the number of micronucleated
      cervical cells between the patients and healthy women. Moreover, significant
      associations were found between micronucleus expression and both the degree of
      uterine lesions (r2=0.7237; r=0.8507; p=0.000002) and viral load (r2=0.7012;
      r=0.8374; p=0.000004). The findings demonstrate the efficacy of micronucleus
      analysis in monitoring risks to human health.

PMID- 25770190
TI  - Cigarette smoke-induced effects on the cell cycle in oral cancer cells: reduction
      of G2/M fraction.
AB  - BACKGROUND: Cigarette smoke (CS) is the main inducer of oral cancer, increasing
      its prevalence by 4-7 times. MATERIALS AND METHODS: We examined the suitability
      of cell models SCC-25 and SCC-15 for studying effects of CS on oral cancer cells
      and whether CS significantly affects the cell cycle using fluorescence-activated
      cell sorting assays. RESULTS: There was significant change in the fraction of SCC
      15 cells in pre-G1 state following CS exposure. At 60 and 90 min, increase in the
      pre-G1 cell fraction was 118% (p<0.05) and 135% (p<0.01) respectively. The G2/M
      cell fraction was significantly lower following CS exposure. At 90 and 120 min
      following CS exposure, the G2/M fraction levels had declined by 44% (p<0.05) and
      34% (p<0.01) respectively. Results for SCC-25 cells were similar. At 90 and 120
      min following CS exposure, the pre-G1 fraction of the cells increased by 230% and
      550%, respectively (p<0.01). At 120 min of CS exposure, the fraction of G2/M
      cells was lower by 47% (p<0.05) compared to controls. CONCLUSION: CS profoundly
      affects the cell-cycle distribution in both SCC-15 and SCC-25 oral cancer
      cellular models. Such effects have been associated with DNA damage and
      carcinogenesis. Both models are useful for studying oral cancer pathogenesis.

PMID- 25770191
TI  - DNA fragmentation induced by cigarette smoke in oral cancer cells.
AB  - BACKGROUND/AIM: Cigarette smoke (CS) is the main inducer of oral cancer,
      increasing the prevalence by 4-7 times. We examined induction of apoptosis by CS
      exposure of SCC-25 and SCC-15 oral cancer cells. MATERIALS AND METHODS: After
      controlled exposure to CS of various durations and at different time points we
      measured DNA fragmentation to assay apoptotic levels. RESULTS: SCC-15 cells
      showed a 70% (p<0.05) increase in apoptotic levels immediately after 30 min of
      exposure to CS. Twenty-four hours after 30-min CS exposure a further increase in
      apoptotic levels to 178% (p<0.05) could be observed. However, SCC-15 cells showed
      a decrease in apoptotic levels immediately after 180-min exposure to CS. CS
      exposed SCC-25 cells did not show such CS-related effects. CONCLUSION: SCC-15 and
      SCC-25 oral cancer cells respond differently to CS regarding apoptotic cell death
      levels. In this respect, SCC-15 cells are sensitive to CS, while SCC-25 cells are
      not. Further comparisons between these cells may give insight regarding
      relationships between CS, apoptosis and invasiveness of oral cancer.

PMID- 25770192
TI  - Comparative proteomic analysis of two stress-management strategies in pancreatic
      cancer.
AB  - BACKGROUND: It is known that cancers adopt different strategies to cope with
      stress and overcome adverse micro-environmental conditions. Such strategies are
      also applicable to chemo-therapeutic treatment, which could subsequently result
      in chemo-resistance. MATERIALS AND METHODS: In order to investigate known stress
      evasion strategies observed in pancreatic cancer, the stress-resistant KLM1
      derived cell lines KLM1-R (Gemcitabine (GEM)-induced stress) and KLM1-S (growth
      factor restriction-induced stress) were employed. Comparative proteomics were
      employed between for the two cell lines that were also compared against the
      parent cell line KLM1. RESULTS: Proteomic analysis revealed changes in the
      expression levels of 6 proteins, namely: transitional endoplasmic reticulum
      ATPase, lamin A/C, PDZ and LIM protein 1, calmodulin, heat shock protein 60 and
      alpha enolase. Resistance to GEM of KLM1-R and KLM1-S was found to be comparable,
      with KLM1-S cells exhibiting close to 1.5-fold higher half-maximal inhibitory
      concentration (IC50) compared to KLM1-R cells. CONCLUSION: These results suggest
      that KLM1-R can be used as a model of directly-acquired chemoresistance
      (responding directly to evade GEM treatment), while KLM1-S is a good model of
      indirectly-acquired chemoresistance (formed in response to having to survive with
      less availability of growth factors), additionally gaining a selective advantage
      upon GEM treatment.

PMID- 25770193
TI  - Comparative proteomics of primary breast carcinomas and lymph node metastases
      outlining markers of tumor invasion.
AB  - BACKGROUND: Lymph node metastasis is an important clinicopathological parameter
      for breast cancer prognostication and treatment. Although the development of
      metastasis is common in axillary lymph nodes, the mechanisms underlying the
      locoregional spread are yet poorly understood. In the present study, we outline
      the involvement of proteins in tumor invasion by comparing the proteome profile
      of primary breast tumors (PBT) against that of lymph node metastasis (LNM).
      PATIENTS AND METHODS: The comparative proteome analyses of seven paired samples
      were performed using two-dimensional gel electrophoresis (2DE) and mass
      spectrometry (MS). RESULTS: Recurrent proteins were differentially expressed in
      PBT and LNM across patients. Higher levels of 1433G, 1433T, K2C8, PSME2, SNAA,
      TPM4, TRFE and VIME were observed in primary tumors compared to the metastatic
      site. On the other hand, higher levels of ALDH2 and GDIR2 were identified in
      metastasis related to tumors. These proteins provide a new insight on breast
      cancer research. CONCLUSION: Our achievements strengthened previous omics-based
      studies and also support the validation of potential markers of tumor invasion
      and metastasis.

PMID- 25770194
TI  - Refining the phenotype of Unverricht-Lundborg disease (EPM1): a population-wide
      Finnish study.
AB  - OBJECTIVE: This Finnish nationwide study aimed to refine the clinical phenotype
      variability and to identify factors that could explain the extensive variability
      in the clinical severity of the symptoms observed among patients with Unverricht
      Lundborg disease (progressive myoclonus epilepsy type 1 [EPM1]) homozygous for
      the dodecamer expansion mutation in the cystatin B (CSTB) gene. METHODS: The
      study population consisted of 66 (33 men and 33 women) patients with genetically
      confirmed EPM1 homozygous for the CSTB expansion mutation for whom the sizes of
      the expanded alleles were determined. The clinical evaluation included
      videorecorded Unified Myoclonus Rating Scale and retrospectively collected
      medical history. The navigated transcranial magnetic stimulation test was used to
      determine motor threshold (MT) and silent period (SP) of the motor cortex.
      RESULTS: An earlier age at onset for EPM1 and longer disease duration were
      associated with more severe action myoclonus, lower performance IQ, increased MT,
      and prolonged SP. The number of dodecamer repeats in CSTB alleles varied between
      38 and 77. On average, the size of the longer expanded alleles of patients was
      independently associated with MT, but exerted only a modulating effect on age at
      onset, myoclonus severity, and SP. CONCLUSIONS: As a group, earlier disease onset
      and longer duration are associated with more severe phenotype. Even though the
      vast majority of patients with EPM1 have a uniform genetic mutation, the actual
      size of the longer CSTB expansion mutation allele is likely to have a modulating
      effect on the age at disease onset, myoclonus severity, and cortical
      neurophysiology.

PMID- 25770195
TI  - Predicting memory change after temporal lobectomy for epilepsy.

PMID- 25770196
TI  - Comment: the environmental and genetic impact of spatial cluster analysis in ALS.

PMID- 25770197
TI  - Spatial cluster analysis of population amyotrophic lateral sclerosis risk in
      Ireland.
AB  - OBJECTIVE: Few spatial cluster analyses of amyotrophic lateral sclerosis (ALS)
      incidence have been conducted on prospective incident population-based cohorts;
      we report results of a formal cluster analysis of the Irish ALS cohort from
      January 1, 1995, to December 31, 2013. METHODS: We identified 1,684 incident
      cases from the Irish ALS register. Population data from 4 census years were used
      to calculate age- and sex-standardized expected ALS cases for 3,355 areas.
      Spatial cluster analysis was performed to identify high-risk clusters using both
      SaTScan and FleXScan software. Poisson-based, time period-stratified statistics
      and time-stratified Bayesian smoothed risk mapping were used to audit
      completeness of case ascertainment of the register. RESULTS: No significant high
      risk clusters of incident ALS were identified. However, SaTScan revealed 2
      significant areas of lower-than-average ALS risk-one centered on County Kilkenny
      (relative risk 0.53, p = 0.012) and a smaller area in County Clare (relative risk
      0.0, p = 0.029). Audit of case ascertainment did not indicate any failure to
      detect cases in these areas. CONCLUSIONS: The absence of high-risk ALS clusters
      in Ireland contrasts with previous studies. Our study has several advantages,
      notably the use of a long-running prospective ALS register with nationwide case
      ascertainment. The presence of 2 low-risk areas was unexpected. No obvious
      ascertainment, demographic, or common environmental factors explain this finding.
      However, we postulate that historical factors may have led to altered genetic
      admixture in these regions, possibly contributing to lower rates.

PMID- 25770198
TI  - Nocturnal frontal lobe epilepsy with paroxysmal arousals due to CHRNA2 loss of
      function.
AB  - OBJECTIVE: We assessed the mutation frequency in nicotinic acetylcholine receptor
      (nAChR) subunits CHRNA4, CHRNB2, and CHRNA2 in a cohort including autosomal
      dominant nocturnal frontal lobe epilepsy (ADNFLE) and sporadic nocturnal frontal
      lobe epilepsy (NFLE). Upon finding a novel mutation in CHRNA2 in a large family,
      we tested in vitro its functional effects. METHODS: We sequenced all the coding
      exons and their flanking intronic regions in 150 probands (73 NFLE, 77 ADNFLE),
      in most of whom diagnosis had been validated by EEG recording of seizures. Upon
      finding a missense mutation in CHRNA2, we measured whole-cell currents in human
      embryonic kidney cells in both wild-type and mutant alpha2beta4 and alpha2beta2
      nAChR subtypes stimulated with nicotine. RESULTS: We found a c.889A>T
      (p.Ile297Phe) mutation in the proband (~0.6% of the whole cohort) of a large
      ADNFLE family (1.2% of familial cases) and confirmed its segregation in all 6
      living affected individuals. Video-EEG studies demonstrated sleep-related
      paroxysmal epileptic arousals in all mutation carriers. Oxcarbazepine treatment
      was effective in all. Whole-cell current density was reduced to about 40% in
      heterozygosity and to 0% in homozygosity, with minor effects on channel
      permeability and sensitivity to nicotine. CONCLUSION: ADNFLE had previously been
      associated with CHRNA2 dysfunction in one family, in which a gain of function
      mutation was demonstrated. We confirm the causative role of CHRNA2 mutations in
      ADNFLE and demonstrate that also loss of function of alpha2 nAChRs may have
      pathogenic effects. CHRNA2 mutations are a rare cause of ADNFLE but this gene
      should be included in mutation screening.

PMID- 25770199
TI  - Memory fMRI predicts verbal memory decline after anterior temporal lobe
      resection.
AB  - OBJECTIVE: To develop a clinically applicable memory functional MRI (fMRI) method
      of predicting postsurgical memory outcome in individual patients. METHODS: In
      this prospective cohort study, 50 patients with temporal lobe epilepsy (23 left)
      and 26 controls underwent an fMRI memory encoding paradigm of words with a
      subsequent out-of-scanner recognition assessment. Neuropsychological assessment
      was performed preoperatively and 4 months after anterior temporal lobe resection,
      and at equal time intervals in controls. An event-related analysis was used to
      explore brain activations for words remembered and change in verbal memory scores
      4 months after surgery was correlated with preoperative activations. Individual
      lateralization indices were calculated within a medial temporal and frontal
      region and compared with other clinical parameters (hippocampal volume,
      preoperative verbal memory, age at onset of epilepsy, and language
      lateralization) as a predictor of verbal memory outcome. RESULTS: In left
      temporal lobe epilepsy patients, left frontal and anterior medial temporal
      activations correlated significantly with greater verbal memory decline, while
      bilateral posterior hippocampal activation correlated with less verbal memory
      decline postoperatively. In a multivariate regression model, left lateralized
      memory lateralization index (>=0.5) within a medial temporal and frontal mask was
      the best predictor of verbal memory outcome after surgery in the dominant
      hemisphere in individual patients. Neither clinical nor functional MRI parameters
      predicted verbal memory decline after nondominant temporal lobe resection.
      CONCLUSION: We propose a clinically applicable memory fMRI paradigm to predict
      postoperative verbal memory decline after surgery in the language-dominant
      hemisphere in individual patients.

PMID- 25770200
TI  - Intrafamilial variability in GMPPB-associated dystroglycanopathy: Broadening of
      the phenotype.

PMID- 25770201
TI  - Applying the CHIME recovery framework in two culturally diverse Australian
      communities: Qualitative results.
AB  - BACKGROUND: CHIME (connectedness, hope and optimism about the future, identity,
      meaning in life and empowerment) is a framework for conceptualising personal
      recovery from mental illness. To date, there has been limited research on its
      cross-cultural applicability. AIMS: To apply CHIME to two culturally diverse
      groups' conceptualisation of recovery from depression. METHOD: Qualitative
      interviews with 30 Anglo-Australians and 28 Indian-Australians living with
      depression in Melbourne, Australia. Data were thematically analysed. RESULTS:
      Both groups valued connectedness but experienced stigma and struggled to broker
      family support. Identity, hope and optimism for the future were associated with
      positive thinking, being 'cured' and discontinuing treatment. Spirituality gave
      Indian participants meaning in life; Anglos derived meaning from the illness
      experience itself. Feeling empowered, for both groups, was related to improved
      socio-economic status and being 'settled' (e.g. having gainful employment, a home
      and family). CONCLUSIONS: CHIME was applicable in both groups, but culture
      mediated how cross-cutting issues (e.g. stigma) and sub-components of CHIME were
      operationalised. Recovery was also influenced by participant's socio-economic
      context. Research, policy and practice implications are discussed.

PMID- 25770202
TI  - Mental health of internally displaced persons in Jalozai camp, Pakistan.
AB  - BACKGROUND: Internal displacement has been a distressing issue of Pakistan for
      last one decade. Few research works have been conducted on the psychological
      issues of internally displaced persons in Pakistan. AIMS: The current research
      was aimed at determining the psychological effects of internal displacement, that
      is, psychological well-being, depression, anxiety and stress (internalizing
      problems) of the individuals who were displaced as a result of an armed conflict
      in Swat. METHOD: A sample of 126 internally displaced persons was taken from
      Jalozai camp which included females (n = 65) and males (n = 61). Age of the
      sample ranged from 20 to 75 years with a mean of 47.5 years. Translated and
      adapted versions of Well-Being Affectometer-2 Scale and Depression Anxiety Stress
      Scale were used in the current research. RESULTS: Results of the study indicated
      differences between males and females, females being higher on internalizing
      problems and lower on psychological well-being, whereas family loss during
      displacement affected the results in the same way. Well-being, gender and family
      loss emerged as significant predictors of internalizing problems, and gender
      moderated the relationship between well-being and internalizing problems.
      CONCLUSION: Internal displacement may bring psychological issues for internally
      displaced persons, that is, their well-being may decrease and depression, anxiety
      and stress may increase during displacement. Limitations and implications of the
      study were discussed further.

PMID- 25770203
TI  - Identifying depressive symptom trajectory groups among Korean adults and
      psychosocial factors as group determinants.
AB  - BACKGROUND: Longitudinal research is needed to examine the depressive symptom
      trajectories of different groups during adulthood and their antecedents and
      consequences, because depressive symptoms may be changeable and heterogeneous
      over time. AIMS: This study examined the number of trajectory groups describing
      the depressive symptoms of Korean adults, as well as the shape of the
      trajectories and the association between trajectory group membership and
      psychosocial factors identified based on the ecosystem model. METHOD: This study
      used Nagin's semi-parametric group-based modeling to analyze Year 1 to Year 7
      data from Korea Welfare Panel Survey (N = 13,735), a nationally representative
      sample of community-dwelling adults. RESULTS: Three distinct trajectory groups
      were identified: a low stable depressive symptoms group, a moderate depressive
      symptoms group and a high depressive symptoms group. Result from multinominal
      logit analysis showed that all psychosocial factors except family relationships
      affected the likelihood of membership in the three depressive symptoms groups.
      Especially, self-esteem was the psychosocial factor with the largest impact on
      depressive symptom trajectory group membership. When screening for depressive
      symptoms, individuals with a low socioeconomic status should be a primary concern
      and intervention should be made available to them. CONCLUSION: Prevention or
      intervention with members of the identified trajectory groups would likely
      require integrative approaches targeting psychosocial factors across multiple
      contexts.

PMID- 25770204
TI  - The attributable burden of panic disorder in the impairment of quality of life in
      a national survey in Italy.
AB  - INTRODUCTION/OBJECTIVE: The aim was to measure the lifetime prevalence of panic
      disorder (PD) in an Italian community sample, and to estimate the burden
      attributable to PD in compromising the quality of life (QoL) of people diagnosed
      with it. METHODS: Community survey was conducted on a sample of 4,999 randomly
      selected adult subjects. Instruments used were semi-structured clinical interview
      Advanced Neuropsychiatric Tools and Assessment Schedule (ANTAS), administered by
      clinicians and allowing diagnosis according to Diagnostic and Statistical Manual
      of Mental Disorder (4th ed.; DSM-IV); Short Form Health Survey (SF-12). RESULTS:
      The lifetime prevalence of PD was 3.6% (4.4% in females, 2.5% in males; p =
      .002). People with PD had a lower SF-12 score than the standardized community
      sample (35.5 +/- 6.5 vs. 38.4 +/- 5.9; p < .0001) with a mean difference
      (attributable burden) of 2.9 +/- 0.7, that is, lower than PD with agoraphobia
      (AP; 4.2 +/- 2.4). Wilson Disease (WD), Multiple Sclerosis, Major Depressive
      Disorder and Eating Disorders (ED) show a higher attributable burden in impaired
      QoL than PD, while the attributable burden of PD with AP is not lower than in ED
      and WD. CONCLUSIONS: The burden attributable to the impairment of QoL following a
      lifetime diagnosis of PD was found to be not so great compared to the impairment
      caused by Major Depressive Disorder (MDD) or neurological conditions. The
      comorbidity of PD with AP worsens QoL significantly.

PMID- 25770206
TI  - Psychological strains and suicide intent: Results from a psychological autopsy
      study with Chinese rural young suicides.
AB  - BACKGROUND: Previous studies have examined the prevalence of psychological
      strains among various suicide populations. However, it is still unexamined
      whether psychological strains can predict suicide intent directly. AIMS: We
      planned to explore the prevalence of psychological strains and analyze the
      relationship between psychological strains and suicide intent among Chinese rural
      young suicides. METHODS: Psychological autopsy method was used to investigate the
      environmental and other factors of rural young suicides. Psychological strains
      were identified from in-depth interviews by the proxy informants of each suicide.
      The first 8 items of Beck's Suicidal Intention Scale (SIS) were used to estimate
      the suicide intent. RESULTS: Results showed that 96.6% of the suicides had at
      least one type of strain, and those suicides who had more strains tended to score
      higher on the suicide intent scale. CONCLUSION: The study further supports that
      suicide intent can be predicted by psychological strains in Chinese rural young
      suicides. The scanning of psychological strains can be used for suicide
      prevention in Chinese rural young suicides.

PMID- 25770205
TI  - Religious psychopathology: The prevalence of religious content of delusions and
      hallucinations in mental disorder.
AB  - BACKGROUND: Religious themes are commonly encountered in delusions and
      hallucinations associated with major mental disorders, and the form and content
      of presentation are significant in relation to both diagnosis and management.
      AIMS: This study aimed to establish what is known about the frequency of
      occurrence of religious delusions (RD) and religious hallucinations (RH) and
      their inter-relationship. METHODS: A review was undertaken of the quantitative
      empirical English literature on RD and RH. RESULTS: A total of 55 relevant
      publications were identified. The lack of critical criteria for defining and
      classifying RD and RH makes comparisons between studies difficult, but prevalence
      clearly varies with time and place, and probably also according to personal
      religiosity. In particular, little is known about the content and frequency of RH
      and the relationship between RH and RD. CONCLUSION: Clearer research criteria are
      needed to facilitate future study of RD and RH, and more research is needed on
      the relationship between RD and RH.

PMID- 25770207
TI  - Determinants of subjective and objective burden of informal caregiving of
      patients with psychotic disorders.
AB  - BACKGROUND: In a previous study, the objective burden of informal caregiving to
      patients with psychotic disorders amounted to 22 hours/week, and the subjective
      burden was huge with predominately anxiety and depression as main symptoms. In
      this study, determinants of the informal caregiving burden are analyzed to find
      foci for interventions to ease the size of burden. METHODS: Patients with
      psychotic disorders (n = 107) and their informal caregivers (n = 118) were
      included. They were assessed with a comprehensive battery of rating scales
      including patient and caregiver characteristics as well as the amount and quality
      of health-care provision. RESULTS: A multiple linear regression analysis showed
      that the subjective burden was significantly lower when patients had higher
      levels of functioning and when the health status of the informal caregivers was
      good. No significant determinants were found for the objective burden, but an
      association was found between a higher socioeconomic status of the caregivers and
      the amount of money provided for the patient. An association was also found
      between a positive perception of caregiving and more hours spent on caregiving.
      CONCLUSION: The functioning level of the patients was the main determinant of the
      subjective burden of informal care. For the objective burden, no main determinant
      was found.

PMID- 25770208
TI  - Type of unit and population served matters when implementing a smoke-free policy
      in mental health settings: Perceptions of unit managers across England.
AB  - BACKGROUND: Globally, smoking remains a significant issue for mental health
      populations. Many mental health trusts in England are facing challenges of
      implementing the National Institute for Health and Care Excellence guidance
      according to which all mental health settings, no matter the type, should be
      entirely smoke-free and provide comprehensive smoking cessation support. AIM: The
      aim of this paper was to determine if unit type and unit manager smoking status
      influence mental health smoke-free policy implementation. METHOD: This paper
      reports on the secondary analysis of data from a cross-sectional survey of 147
      mental health inpatient settings in England, in 2010. The original study's main
      aim was to understand unit managers' perceived reasons for success or failure of
      smoke-free policy. RESULTS: Unit managers (n = 131) held a positive stance
      towards supporting smoke-free policy and most perceived that the policy was
      successful. Non-smoker unit managers were more likely to adopt complete bans than
      smoker unit managers, whereas smoker unit managers were more likely than non
      smoker unit managers to think that stopping smoking aggravated patients' mental
      illness. Smoking rates for staff and patients remain high, as perceived by unit
      managers, regardless of unit type. Proportion of units offering nicotine
      replacement therapy and peer support to patients was significantly higher in
      locked units compared to semi-locked or residential rehabilitation. Applied
      strategies significantly vary by type of unit, whereas unit managers' knowledge,
      attitude and practices vary by their smoking status. DISCUSSION: There are
      nuanced differences in how smoke-free policy is enacted which vary by unit type.
      These variations recognise the differing contexts of care provision in different
      types of units serving different patient groups. Addressing staff smoking rates,
      promoting consistency of staff response to patients' smoking and providing staff
      education and support continue to be key strategies to successful smoke-free
      policy. CONCLUSIONS: Our results demonstrate the importance of taking into
      account the type of unit and acuity of patients when enacting smoke-free policy
      and addressing staff smoking.

PMID- 25770209
TI  - Histone deacetylase 6 (HDAC6) promotes the pro-survival activity of 14-3-3zeta
      via deacetylation of lysines within the 14-3-3zeta binding pocket.
AB  - The phospho-binding protein 14-3-3zeta acts as a signaling hub controlling a
      network of interacting partners and oncogenic pathways. We show here that lysines
      within the 14-3-3zeta binding pocket and protein-protein interface can be
      modified by acetylation. The positive charge on two of these lysines, Lys(49) and
      Lys(120), is critical for coordinating 14-3-3zeta-phosphoprotein interactions.
      Through screening, we identified HDAC6 as the Lys(49)/Lys(120) deacetylase.
      Inhibition of HDAC6 blocks 14-3-3zeta interactions with two well described
      interacting partners, Bad and AS160, which triggers their dephosphorylation at
      Ser(112) and Thr(642), respectively. Expression of an acetylation-refractory
      K49R/K120R mutant of 14-3-3zeta rescues both the HDAC6 inhibitor-induced loss of
      interaction and Ser(112)/Thr(642) phosphorylation. Furthermore, expression of the
      K49R/K120R mutant of 14-3-3zeta inhibits the cytotoxicity of HDAC6 inhibition.
      These data demonstrate a novel role for HDAC6 in controlling 14-3-3zeta binding
      activity. 

PMID- 25770210
TI  - The mechanoenzymatic core of dynamin-related protein 1 comprises the minimal
      machinery required for membrane constriction.
AB  - Mitochondria are dynamic organelles that continually undergo cycles of fission
      and fusion. Dynamin-related protein 1 (Drp1), a large GTPase of the dynamin
      superfamily, is the main mediator of mitochondrial fission. Like prototypical
      dynamin, Drp1 is composed of a mechanochemical core consisting of the GTPase,
      middle, and GTPase effector domain regions. In place of the pleckstrin homology
      domain in dynamin, however, Drp1 contains an unstructured variable domain, whose
      function is not yet fully resolved. Here, using time-resolved EM and rigorous
      statistical analyses, we establish the ability of full-length Drp1 to constrict
      lipid bilayers through a GTP hydrolysis-dependent mechanism. We also show the
      variable domain limits premature Drp1 assembly in solution and promotes membrane
      curvature. Furthermore, the mechanochemical core of Drp1, absent of the variable
      domain, is sufficient to mediate GTP hydrolysis-dependent membrane constriction. 

PMID- 25770211
TI  - Convergence of melatonin and serotonin (5-HT) signaling at MT2/5-HT2C receptor
      heteromers.
AB  - Inasmuch as the neurohormone melatonin is synthetically derived from serotonin (5
      HT), a close interrelationship between both has long been suspected. The present
      study reveals a hitherto unrecognized cross-talk mediated via physical
      association of melatonin MT2 and 5-HT2C receptors into functional heteromers.
      This is of particular interest in light of the "synergistic" melatonin agonist/5
      HT2C antagonist profile of the novel antidepressant agomelatine. A suite of co
      immunoprecipitation, bioluminescence resonance energy transfer, and
      pharmacological techniques was exploited to demonstrate formation of functional
      MT2 and 5-HT2C receptor heteromers both in transfected cells and in human cortex
      and hippocampus. MT2/5-HT2C heteromers amplified the 5-HT-mediated
      Gq/phospholipase C response and triggered melatonin-induced unidirectional
      transactivation of the 5-HT2C protomer of MT2/5-HT2C heteromers. Pharmacological
      studies revealed distinct functional properties for agomelatine, which shows
      "biased signaling." These observations demonstrate the existence of functionally
      unique MT2/5-HT2C heteromers and suggest that the antidepressant agomelatine has
      a distinctive profile at these sites potentially involved in its therapeutic
      effects on major depression and generalized anxiety disorder. Finally, MT2/5-HT2C
      heteromers provide a new strategy for the discovery of novel agents for the
      treatment of psychiatric disorders. 

PMID- 25770212
TI  - DDIT3 and KAT2A Proteins Regulate TNFRSF10A and TNFRSF10B Expression in
      Endoplasmic Reticulum Stress-mediated Apoptosis in Human Lung Cancer Cells.
AB  - TNFRSF10A and TNFRSF10B are cell surface receptors that bind to tumor necrosis
      factor-related apoptosis-inducing ligand (TRAIL) and mediate the extrinsic
      pathway of apoptosis. However, the mechanisms of transcriptional regulation of
      TNFRSF10A and TNFRSF10B remain largely uncharacterized. In this study, two
      putative DDIT3 binding sites (-1636/-1625; -374/-364) and a putative AP-1 binding
      site (-304/-298) were identified in the TNFRSF10A promoter region. We found that
      DDIT3 interacts with phospho-JUN, and the DDIT3.phospho-JUN complex binds to the
      AP-1 binding site (-304/-298) within the TNFRSF10A promoter region. In addition,
      we confirmed that KAT2A physically interacts with the N-terminal region (amino
      acids 1-26) of DDIT3. Importantly, knockdown of KAT2A down-regulated TNFRSF10A
      and TNFRSF10B and dramatically decreased promoter activity of cells transfected
      with luciferase reporter plasmid containing the AP-1 binding site (-304/-298) of
      the TNFRSF10A promoter, as well as cells transfected with luciferase reporter
      plasmid containing DDIT3 binding site (-276/-264) of the TNFRSF10B promoter. ChIP
      results suggest that KAT2A may participate in a KAT2A.DDIT3.phospho-JUN complex,
      or may participate in a KAT2A.DDIT3 complex and acetylate H3K9/K14, respectively.
      Moreover, we verified that TNFRSF10A mediates apoptosis triggered by endoplasmic
      reticulum stress in human lung cancer cells. Collectively, we demonstrate that
      DDIT3 and KAT2A cooperatively up-regulate TNFRSF10A and TNFRSF10B. Our findings
      highlight novel mechanisms underlying endoplasmic reticulum stress-induced
      TNFRSF10A and TNFRSF10B expressions and apoptosis. These findings will be helpful
      for elucidating mechanisms related to anticancer drugs in mediating apoptosis. 

PMID- 25770213
TI  - Sodium-calcium exchanger 1 regulates epithelial cell migration via calcium
      dependent extracellular signal-regulated kinase signaling.
AB  - Na(+)/Ca(2+) exchanger-1 (NCX1) is a major calcium extrusion mechanism in renal
      epithelial cells enabling the efflux of one Ca(2+) ion and the influx of three
      Na(+) ions. The gradient for this exchange activity is provided by Na,K-ATPase, a
      hetero-oligomer consisting of a catalytic alpha-subunit and a regulatory beta
      subunit (Na,K-beta) that also functions as a motility and tumor suppressor. We
      showed earlier that mice with heart-specific ablation (KO) of Na,K-beta had a
      specific reduction in NCX1 protein and were ouabain-insensitive. Here, we
      demonstrate that Na,K-beta associates with NCX1 and regulates its localization to
      the cell surface. Madin-Darby canine kidney cells with Na,K-beta knockdown have
      reduced NCX1 protein and function accompanied by 2.1-fold increase in free
      intracellular calcium and a corresponding increase in the rate of cell migration.
      Increased intracellular calcium up-regulated ERK1/2 via calmodulin-dependent
      activation of PI3K. Both myosin light chain kinase and Rho-associated kinase
      acted as mediators of ERK1/2-dependent migration. Restoring NCX1 expression in
      beta-KD cells reduced migration rate and ERK1/2 activation, suggesting that NCX1
      functions downstream of Na,K-beta in regulating cell migration. In parallel,
      inhibition of NCX1 by KB-R7943 in Madin-Darby canine kidney cells, LLC-PK1, and
      human primary renal epithelial cells (HREpiC) increased ERK1/2 activation and
      cell migration. This increased migration was associated with high myosin light
      chain phosphorylation by PI3K/ERK-dependent mechanism in HREpiC cells. These data
      confirm the role of NCX1 activity in regulating renal epithelial cell migration. 

PMID- 25770214
TI  - Structural and Functional Diversity of Peptide Toxins from Tarantula Haplopelma
      hainanum (Ornithoctonus hainana) Venom Revealed by Transcriptomic, Peptidomic,
      and Patch Clamp Approaches.
AB  - Spider venom is a complex mixture of bioactive peptides to subdue their prey.
      Early estimates suggested that over 400 venom peptides are produced per species.
      In order to investigate the mechanisms responsible for this impressive diversity,
      transcriptomics based on second generation high throughput sequencing was
      combined with peptidomic assays to characterize the venom of the tarantula
      Haplopelma hainanum. The genes expressed in the venom glands were identified, and
      the bioactivity of their protein products was analyzed using the patch clamp
      technique. A total of 1,136 potential toxin precursors were identified that
      clustered into 90 toxin groups, of which 72 were novel. The toxin peptides
      clustered into 20 cysteine scaffolds that included between 4 and 12 cysteines,
      and 14 of these groups were newly identified in this spider. Highly abundant
      toxin peptide transcripts were present and resulted from hypermutation and/or
      fragment insertion/deletion. In combination with variable post-translational
      modifications, this genetic variability explained how a limited set of genes can
      generate hundreds of toxin peptides in venom glands. Furthermore, the
      intraspecies venom variability illustrated the dynamic nature of spider venom and
      revealed how complex components work together to generate diverse bioactivities
      that facilitate adaptation to changing environments, types of prey, and milking
      regimes in captivity. 

PMID- 25770215
TI  - Role for Tyrosine Phosphorylation of A-kinase Anchoring Protein 8 (AKAP8) in Its
      Dissociation from Chromatin and the Nuclear Matrix.
AB  - Protein-tyrosine phosphorylation regulates a wide variety of cellular processes
      at the plasma membrane. Recently, we showed that nuclear tyrosine kinases induce
      global nuclear structure changes, which we called chromatin structural changes.
      However, the mechanisms are not fully understood. In this study we identify
      protein kinase A anchoring protein 8 (AKAP8/AKAP95), which associates with
      chromatin and the nuclear matrix, as a nuclear tyrosine-phosphorylated protein.
      Tyrosine phosphorylation of AKAP8 is induced by several tyrosine kinases, such as
      Src, Fyn, and c-Abl but not Syk. Nucleus-targeted Lyn and c-Src strongly
      dissociate AKAP8 from chromatin and the nuclear matrix in a kinase activity
      dependent manner. The levels of tyrosine phosphorylation of AKAP8 are decreased
      by substitution of multiple tyrosine residues on AKAP8 into phenylalanine.
      Importantly, the phenylalanine mutations of AKAP8 inhibit its dissociation from
      nuclear structures, suggesting that the association/dissociation of AKAP8
      with/from nuclear structures is regulated by its tyrosine phosphorylation.
      Furthermore, the phenylalanine mutations of AKAP8 suppress the levels of nuclear
      tyrosine kinase-induced chromatin structural changes. In contrast, AKAP8
      knockdown increases the levels of chromatin structural changes. Intriguingly,
      stimulation with hydrogen peroxide induces chromatin structural changes
      accompanied by the dissociation of AKAP8 from nuclear structures. These results
      suggest that AKAP8 is involved in the regulation of chromatin structural changes
      through nuclear tyrosine phosphorylation. 

PMID- 25770216
TI  - G Protein-coupled Receptor Kinases of the GRK4 Protein Subfamily Phosphorylate
      Inactive G Protein-coupled Receptors (GPCRs).
AB  - G protein-coupled receptor (GPCR) kinases (GRKs) play a key role in homologous
      desensitization of GPCRs. It is widely assumed that most GRKs selectively
      phosphorylate only active GPCRs. Here, we show that although this seems to be the
      case for the GRK2/3 subfamily, GRK5/6 effectively phosphorylate inactive forms of
      several GPCRs, including beta2-adrenergic and M2 muscarinic receptors, which are
      commonly used as representative models for GPCRs. Agonist-independent GPCR
      phosphorylation cannot be explained by constitutive activity of the receptor or
      membrane association of the GRK, suggesting that it is an inherent ability of
      GRK5/6. Importantly, phosphorylation of the inactive beta2-adrenergic receptor
      enhanced its interactions with arrestins. Arrestin-3 was able to discriminate
      between phosphorylation of the same receptor by GRK2 and GRK5, demonstrating
      preference for the latter. Arrestin recruitment to inactive phosphorylated GPCRs
      suggests that not only agonist activation but also the complement of GRKs in the
      cell regulate formation of the arrestin-receptor complex and thereby G protein
      independent signaling. 

PMID- 25770217
TI  - Spatial proximity of homologous alleles and long noncoding RNAs regulate a switch
      in allelic gene expression.
AB  - Physiological processes rely on the regulation of total mRNA levels in a cell. In
      diploid organisms, the transcriptional activation of one or both alleles of a
      gene may involve trans-allelic interactions that provide a tight spatial and
      temporal level of gene expression regulation. The mechanisms underlying such
      interactions still remain poorly understood. Here, we demonstrate that
      lipopolysaccharide stimulation of murine macrophages rapidly resulted in the
      actin-mediated and transient homologous spatial proximity of Tnfalpha alleles,
      which was necessary for the mono- to biallelic switch in gene expression. We
      identified two new complementary long noncoding RNAs transcribed from the
      TNFalpha locus and showed that their knockdown had opposite effects in Tnfalpha
      spatial proximity and allelic expression. Moreover, the observed spatial
      proximity of Tnfalpha alleles depended on pyruvate kinase muscle isoform 2 (PKM2)
      and T-helper-inducing POZ-Kruppel-like factor (ThPOK). This study suggests a role
      for lncRNAs in the regulation of somatic homologous spatial proximity and allelic
      expression control necessary for fine-tuning mammalian immune responses. 

PMID- 25770219
TI  - Global warming-accelerated drying in the tropics.

PMID- 25770218
TI  - Community participation in biofilm matrix assembly and function.
AB  - Biofilms of the fungus Candida albicans produce extracellular matrix that confers
      such properties as adherence and drug resistance. Our prior studies indicate that
      the matrix is complex, with major polysaccharide constituents being alpha-mannan,
      beta-1,6 glucan, and beta-1,3 glucan. Here we implement genetic, biochemical, and
      pharmacological approaches to unravel the contributions of these three
      constituents to matrix structure and function. Interference with synthesis or
      export of any one polysaccharide constituent altered matrix concentrations of
      each of the other polysaccharides. Each of these was also required for matrix
      function, as assessed by assays for sequestration of the antifungal drug
      fluconazole. These results indicate that matrix biogenesis entails coordinated
      delivery of the individual matrix polysaccharides. To understand whether
      coordination occurs at the cellular level or the community level, we asked
      whether matrix-defective mutant strains could be coaxed to produce functional
      matrix through biofilm coculture. We observed that mixed biofilms inoculated with
      mutants containing a disruption in each polysaccharide pathway had restored
      mature matrix structure, composition, and biofilm drug resistance. Our results
      argue that functional matrix biogenesis is coordinated extracellularly and thus
      reflects the cooperative actions of the biofilm community. 

PMID- 25770221
TI  - Gait and speed selection in slender inertial swimmers.
AB  - Inertial swimmers use flexural movements to push water and generate thrust. We
      quantify this dynamical process for a slender body in a fluid by accounting for
      passive elasticity and hydrodynamics and active muscular force generation and
      proprioception. Our coupled elastohydrodynamic model takes the form of a
      nonlinear eigenvalue problem for the swimming speed and locomotion gait. The
      solution of this problem shows that swimmers use quantized resonant interactions
      with the fluid environment to enhance speed and efficiency. Thus, a fish is like
      an optimized diode that converts a prescribed alternating transverse motion to
      forward motion. Our results also allow for a broad comparative view of swimming
      locomotion and provide a mechanistic basis for the empirical relation linking the
      swimmer's speed U, length L, and tail beat frequency f, given by U/L ~ f
      [Bainbridge R (1958) J Exp Biol 35:109-133]. Furthermore, we show that a simple
      form of proprioceptive sensory feedback, wherein local muscle activation is
      function of body curvature, suffices to drive elastic instabilities associated
      with thrust production and leads to a spontaneous swimming gait without the need
      for a central pattern generator. Taken together, our results provide a simple
      mechanistic view of swimming consistent with natural observations and suggest
      ways to engineer artificial swimmers for optimal performance.

PMID- 25770220
TI  - Myosin VI regulates gene pairing and transcriptional pause release in T cells.
AB  - Naive CD4 T cells differentiate into several effector lineages, which generate a
      stronger and more rapid response to previously encountered immunological
      challenges. Although effector function is a key feature of adaptive immunity, the
      molecular basis of this process is poorly understood. Here, we investigated the
      spatiotemporal regulation of cytokine gene expression in resting and restimulated
      effector T helper 1 (Th1) cells. We found that the Lymphotoxin (LT)/TNF alleles,
      which encode TNF-alpha, were closely juxtaposed shortly after T-cell receptor
      (TCR) engagement, when transcription factors are limiting. Allelic pairing
      required a nuclear myosin, myosin VI, which is rapidly recruited to the LT/TNF
      locus upon restimulation. Furthermore, transcription was paused at the TNF locus
      and other related genes in resting Th1 cells and released in a myosin VI
      dependent manner following activation. We propose that homologous pairing and
      myosin VI-mediated transcriptional pause release account for the rapid and
      efficient expression of genes induced by an external stimulus. 

PMID- 25770222
TI  - News feature: Space fossils.

PMID- 25770223
TI  - Reply to Liu et al.: Loss of TGF-beta signaling in CARASIL pathogenesis.

PMID- 25770224
TI  - Loss of HtrA1-induced attenuation of TGF-beta signaling in fibroblasts might not
      be the main mechanism of CARASIL pathogenesis.

PMID- 25770225
TI  - Correction. An evaluation of the performance of the NHS Health Check programme in
      identifying people at high risk of developing type 2 diabetes.

PMID- 25770226
TI  - Understanding the causes of intravenous medication administration errors in
      hospitals: a qualitative critical incident study.
AB  - OBJECTIVES: To investigate the underlying causes of intravenous medication
      administration errors (MAEs) in National Health Service (NHS) hospitals. SETTING:
      Two NHS teaching hospitals in the North West of England. PARTICIPANTS: Twenty
      nurses working in a range of inpatient clinical environments were identified and
      recruited using purposive sampling at each study site. PRIMARY OUTCOME MEASURES:
      Semistructured interviews were conducted with nurse participants using the
      critical incident technique, where they were asked to discuss perceived causes of
      intravenous MAEs that they had been directly involved with. Transcribed
      interviews were analysed using the Framework approach and emerging themes were
      categorised according to Reason's model of accident causation. RESULTS: In total,
      21 intravenous MAEs were discussed containing 23 individual active failures which
      included slips and lapses (n=11), mistakes (n=8) and deliberate violations of
      policy (n=4). Each active failure was associated with a range of error and
      violation provoking conditions. The working environment was implicated when
      nurses lacked healthcare team support and/or were exposed to a perceived
      increased workload during ward rounds, shift changes or emergencies. Nurses
      frequently reported that the quality of intravenous dose-checking activities was
      compromised due to high perceived workload and working relationships. Nurses
      described using approaches such as subconscious functioning and prioritising to
      manage their duties, which at times contributed to errors. CONCLUSIONS: Complex
      interactions between active and latent failures can lead to intravenous MAEs in
      hospitals. Future interventions may need to be multimodal in design in order to
      mitigate these risks and reduce the burden of intravenous MAEs.

PMID- 25770228
TI  - Application of a tool for the evaluation of public and patient involvement in
      research.
AB  - OBJECTIVES: Public and patient involvement (PPI) is required at all stages of
      research by many funding bodies such as the National Institute for Health
      Research (NIHR). Given the high priority of PPI within NIHR programmes and the
      associated costs, it is important that the process of involvement and impact of
      PPI on health services research is evaluated. We aimed to develop a tool to
      quantitatively evaluate the quality of PPI in research from a PPI participant's
      perspective in order to inform the researchers about absolute level of quality
      (cross-sectional aspect) and changes in quality over time (longitudinal aspect).
      SETTING: A primary care patient safety translational research centre.
      PARTICIPANTS: The 12 members of the Research User Group (RUG) of Greater
      Manchester Primary Care Patient Safety Translational Research Centre.
      INTERVENTIONS: By their own choice each RUG member supported a specific research
      theme. The level of involvement varied from commenting on documents through to
      designing their own research projects. PRIMARY AND SECONDARY OUTCOME MEASURES
      PLANNED: Measure absolute score and change in score over time in a nine-point
      Likert score within individuals. Compare Likert scores before undertaking PPI
      with scores after PPI activities. Evaluate the usefulness of a questionnaire
      based on a theoretical framework of personal and research factors. RESULTS: The
      questionnaire had an acceptable to good level of internal consistency (Cronbach's
      alpha 0.74-0.81). The majority of the individuals met their initial expectations
      (11/12) and scored high across all factors. There was no significant change over
      time in the aggregate score over all factors and all individuals, but there were
      differences within individuals and factors. A ceiling effect limited the
      questionnaire's usefulness to measure increasing scores. CONCLUSIONS: The
      questionnaire has been useful in evaluating the early stages of a PPI group and
      may be generalisable to another setting.

PMID- 25770227
TI  - Increasing the value of health research in the WHO African Region beyond 2015-
      reflecting on the past, celebrating the present and building the future: a
      bibliometric analysis.
AB  - OBJECTIVE: To assess the profile and determinants of health research productivity
      in Africa since the onset of the new millennium. DESIGN: Bibliometric analysis.
      DATA COLLECTION AND SYNTHESIS: In November 2014, we searched PubMed for articles
      published between 2000 and 2014 from the WHO African Region, and obtained country
      level indicators from World Bank data. We used Poisson regression to examine time
      trends in research publications and negative binomial regression to explore
      determinants of research publications. RESULTS: We identified 107,662
      publications, with a median of 727 per country (range 25-31,757). Three countries
      (South Africa, Nigeria and Kenya) contributed 52% of the publications. The number
      of publications increased from 3623 in 2000 to 12,709 in 2014 (relative growth
      251%). Similarly, the per cent share of worldwide research publications per year
      increased from 0.7% in 2000 to 1.3% in 2014. The trend analysis was also
      significant to confirm a continuous increase in health research publications from
      Africa, with productivity increasing by 10.3% per year (95% CIs +10.1% to
      +10.5%). The only independent predictor of publication outputs was national gross
      domestic product. For every one log US$ billion increase in gross domestic
      product, research publications rose by 105%: incidence rate ratio (IRR=2.05, 95%
      CI 1.39 to 3.04). The association of private health expenditure with publications
      was only marginally significant (IRR=1.86, 95% CI 1.00 to 3.47). CONCLUSIONS:
      There has been a significant improvement in health research in the WHO African
      Region since 2000, with some individual countries already having strong research
      profiles. Countries of the region should implement the WHO Strategy on Research
      for Health: reinforcing the research culture (organisation); focusing research on
      key health challenges (priorities); strengthening national health research
      systems (capacity); encouraging good research practice (standards); and
      consolidating linkages between health research and action (translation).

PMID- 25770229
TI  - Surgical learning curves and operative efficiency: a cross-specialty
      observational study.
AB  - OBJECTIVES: To evaluate the learning curves of three high-volume procedures, from
      distinct surgical specialties. SETTING: Tertiary care academic hospital.
      PARTICIPANTS: A prospectively collected database comprising all medical records
      of patients undergoing isolated coronary artery bypass grafting (CABG), total
      knee replacement (TKR) and bilateral reduction mammoplasty (BRM) at the Brigham
      and Women's Hospital, USA, 1996-2010. Multivariate generalised estimating
      equation (GEE) regression models were used to adjust for patient risk and
      clustering of procedures by surgeon. PRIMARY OUTCOME MEASURE: Operative
      efficiency. RESULTS: A total of 1052 BRMs, 3254 CABGs and 3325 TKRs performed by
      30 surgeons were analysed. Median number of procedures per surgeon was 61 (range
      11-502), 290 (52-973) and 99 (10-1871) for BRM, CABG and TKR, respectively. Mean
      operative times were 134.4 (SD 34.5), 180.9 (62.3) and 101.9 (30.3) minutes,
      respectively. For each procedure, attending surgeon experience was associated
      with significant reductions in operative time (p<0.05). After 15 years of
      experience, BRM operative time decreased by 69.8 min (38.3%), CABG operative time
      decreased by 17.5 min (7.8%) and TKR operative time decreased by 94.4 min
      (48.4%). CONCLUSIONS: Common trends in surgical learning exist. Dependent on the
      procedure, experience can serve as a powerful driver of improvement or have
      clinically insignificant impacts on operative time.

PMID- 25770230
TI  - Examining the relationship between neighbourhood deprivation and mental health
      service use of immigrants in Ontario, Canada: a cross-sectional study.
AB  - OBJECTIVE: While newcomers are often disproportionately concentrated in
      disadvantaged areas, little attention is given to the effects of immigrants'
      postimmigration context on their mental health and care use. Intersectionality
      theory suggests that understanding the full impact of disadvantage requires
      considering the effects of interacting factors. This study assessed the inter
      relationship between recent immigration status, living in deprived areas and
      service use for non-psychotic mental health disorders. STUDY DESIGN: Matched
      population-based cross-sectional study. SETTING: Ontario, Canada, where
      healthcare use data for 1999-2012 were linked to immigration data and area-based
      material deprivation scores. PARTICIPANTS: Immigrants in urban Ontario, and their
      age-matched and sex-matched long-term residents (a group of Canadian-born or long
      term immigrants, n=501,417 pairs). PRIMARY AND SECONDARY OUTCOME MEASURES: For
      immigrants and matched long-term residents, contact with primary care,
      psychiatric care and hospital care (emergency department visits or inpatient
      admissions) for non-psychotic mental health disorders was followed for 5 years
      and examined using conditional logistic regression models. Intersectionality was
      investigated by including a material deprivation quintile by immigrant status
      (immigrant vs long-term resident) interaction. RESULTS: Recent immigrants in
      urban Ontario were more likely than long-term residents to live in most deprived
      quintiles (immigrants--males: 22.8%, females: 22.3%; long-term residents--both
      sexes: 13.1%, p<0.001). Living in more deprived circumstances was associated with
      greater use of mental health services, but increases were smaller for immigrants
      than for long-term residents. Immigrants used less mental health services than
      long-term residents. CONCLUSIONS: This study adds to existing research by
      suggesting that immigrant status and deprivation have a combined effect on recent
      immigrants' care use for non-psychotic mental health disorders. In settings where
      immigrants are over-represented in deprived areas, policymakers focused on
      increasing immigrants' access of mental health services should broadly address
      the influence of structural and cultural factors beyond the disadvantage.

PMID- 25770231
TI  - Barriers to early diagnosis of symptomatic breast cancer: a qualitative study of
      Black African, Black Caribbean and White British women living in the UK.
AB  - OBJECTIVES: Understanding barriers to early diagnosis of symptomatic breast
      cancer among Black African, Black Caribbean and White British women in the UK.
      DESIGN: In-depth qualitative interviews using grounded theory methods to identify
      themes. Findings validated through focus groups. PARTICIPANTS: 94 women aged 33
      91 years; 20 Black African, 20 Black Caribbean and 20 White British women
      diagnosed with symptomatic breast cancer were interviewed. Fourteen Black African
      and 20 Black Caribbean women with (n=19) and without (n=15) breast cancer
      participated in six focus groups. SETTING: Eight cancer centres/hospital trusts
      in London (n=5), Somerset (n=1), West Midlands (n=1) and Greater Manchester (n=1)
      during 2012-2013. RESULTS: There are important differences and similarities in
      barriers to early diagnosis of breast cancer between Black African, Black
      Caribbean and White British women in the UK. Differences were influenced by
      country of birth, time spent in UK and age. First generation Black African women
      experienced most barriers and longest delays. Second generation Black Caribbean
      and White British women were similar and experienced fewest barriers. Absence of
      pain was a barrier for Black African and Black Caribbean women. Older White
      British women (>=70 years) and first generation Black African and Black Caribbean
      women shared conservative attitudes and taboos about breast awareness. All women
      viewed themselves at low risk of the disease, and voiced uncertainty over breast
      awareness and appraising non-lump symptoms. Focus group findings validated and
      expanded themes identified in interviews. CONCLUSIONS: Findings challenged
      reporting of Black women homogenously in breast cancer research. This can mask
      distinctions within and between ethnic groups. Current media and health promotion
      messages need reframing to promote early presentation with breast symptoms.
      Working with communities and developing culturally appropriate materials may
      lessen taboos and stigma, raise awareness, increase discussion of breast cancer
      and promote prompt help-seeking for breast symptoms among women with low cancer
      awareness.

PMID- 25770232
TI  - Predictors of intentions to quit smoking in Aboriginal tobacco smokers of
      reproductive age in regional New South Wales (NSW), Australia: quantitative and
      qualitative findings of a cross-sectional survey.
AB  - OBJECTIVES: To assess the predictors of intentions to quit smoking in a community
      sample of Aboriginal smokers of reproductive age, in whom smoking prevalence is
      slow to decline. DESIGN, SETTING AND PARTICIPANTS: A cross-sectional survey
      involved 121 Aboriginal smokers, aged 18-45 years from January to May 2014,
      interviewed at community events on the Mid-North Coast NSW. Qualitative and
      quantitative data were collected on smoking and quitting attitudes, behaviours
      and home smoking rules. Perceived efficacy for quitting, and perceived threat
      from smoking, were uniquely assessed with a validated Risk Behaviour Diagnosis
      (RBD) Scale. MAIN OUTCOME MEASURES: Logistic regression explored the impact of
      perceived efficacy, perceived threat and consulting previously with a doctor or
      health professional (HP) on self-reported intentions to quit smoking, controlling
      for potential confounders, that is, protection responses and fear control
      responses, home smoking rules, gender and age. Participants' comments regarding
      smoking and quitting were investigated via inductive analysis, with the
      assistance of Aboriginal researchers. RESULTS: Two-thirds of smokers intended to
      quit within 3 months. Perceived efficacy (OR=4.8; 95% CI 1.78 to 12.93) and
      consulting previously with a doctor/HP about quitting (OR=3.82; 95% CI 1.43 to
      10.2) were significant predictors of intentions to quit. 'Smoking is not doing
      harm right now' was inversely associated with quit intentions (OR=0.25; 95% CI
      0.08 to 0.8). Among those who reported making a quit attempt, after consulting
      with a doctor/HP, 40% (22/60) rated the professional support received as low (0
      2/10). Qualitative themes were: the negatives of smoking (ie, disgust, regret,
      dependence and stigma), health effects and awareness, quitting, denial, 'smoking
      helps me cope' and social aspects of smoking. CONCLUSIONS: Perceived efficacy and
      consulting with a doctor/HP about quitting may be important predictors of
      intentions to quit smoking in Aboriginal smokers of reproductive age.
      Professional support was generally perceived to be low; thus, it could be
      improved for these Aboriginal smokers. Aboriginal participants expressed strong
      sentiments about smoking and quitting.

PMID- 25770233
TI  - Synergistic effect of interaction between perceived health and social activity on
      depressive symptoms in the middle-aged and elderly: a population-based
      longitudinal study.
AB  - OBJECTIVE: To examine the synergistic effect of interaction between perceived
      health and social activity on depressive symptoms. METHODS: We investigated
      whether the interaction between perceived health and social activity has a
      synergistic effect on depressive symptoms in the middle-aged and elderly using
      data from 6590 respondents aged 45 and older in the Korean Longitudinal Study on
      Aging (KLoSA), 2006-2012. A generalised linear mixed-effects model was used to
      investigate the association in a longitudinal data form. Depressive symptoms were
      measured using the Center for Epidemiological Studies Depression 10 Scale (CES
      D10). Perceived health and level of social activity were categorical variables
      with three values. Participation in six social activities was assessed. RESULTS:
      Interactions between perceived health status and social activity were
      statistically significant for almost all social activity/perceived health
      combinations. Addition of the interaction term significantly decreased CES-D10
      scores, confirming the synergistic effect of the interaction between perceived
      health status and social activity ('normal*moderate', beta=-0.1826;
      'poor*moderate', beta=-0.5739; 'poor*active', beta=-0.8935). In addition, we
      performed stratified analyses by region: urban or rural. In urban respondents,
      the additional effect of the interaction term decreased CES-D10 scores and all
      social activity/perceived health combinations were statistically significant
      ('normal*moderate', beta=-0.2578; 'normal*active', beta=-0.3945; 'poor*moderate',
      beta=-0.5739; 'poor*active', beta=-0.8935). In rural respondents, only one social
      activity/perceived health combination was statistically significant, and the
      additional effect of the interaction term showed no consistent trend on CES-D10
      scores. CONCLUSIONS: The interaction between perceived health and social activity
      has a synergistic effect on depressive symptoms; the additional effect of the
      interaction term significantly decreased CES-D10 scores in our models.

PMID- 25770234
TI  - The effects of prenatal cannabis exposure on fetal development and pregnancy
      outcomes: a protocol.
AB  - INTRODUCTION: The effects of exposure to marijuana in utero on fetal development
      are not clear. Given that the recent legislation on cannabis in the US is likely
      to result in increased use, there is a need to assess the effects of prenatal
      cannabis exposure on fetal development and pregnancy outcomes. The objective of
      this review is to assess the effects of prenatal exposure to cannabis on
      pregnancy outcomes (including maternal and child outcomes). METHODS AND ANALYSES:
      Major databases will be searched from inception to the latest issue, with the aim
      of identifying studies that reported the effects of prenatal exposure to cannabis
      on fetal development and pregnancy outcomes. Two investigators will independently
      review all titles and abstracts to identify potential articles. Discrepancies
      will be resolved by repeated review, discussion and consensus. Study quality
      assessment will be undertaken, using standard protocols. To qualify for
      inclusion, studies must report at least one maternal or neonatal outcome post
      partum. Cross-sectional, case-control, cohort and randomised controlled trials
      published in English will be included. In order to rule out the effects of other
      drugs that may affect fetal development and pregnancy outcomes, studies will only
      be included if they report outcomes of prenatal exposure to cannabis while
      excluding other illicit substances. Data from eligible studies will be extracted,
      and data analysis will include a systematic review and critical appraisal of
      evidence, and meta-analysis if data permit. Meta-analysis will be conducted if
      three or more studies report comparable statistics on the same outcome. ETHICS
      AND DISSEMINATION: The review which will result from this protocol has not
      already been conducted. Preparation of the review will follow the procedures
      stated in this protocol, and will adhere to the Preferred Reporting Items for
      Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Ethical approval of
      data will not be required since the review will use data that are already
      available in the public domain through published articles and other reports.

PMID- 25770236
TI  - Introductory paragraph.

PMID- 25770235
TI  - Monetary costs of agitation in older adults with Alzheimer's disease in the UK:
      prospective cohort study.
AB  - OBJECTIVE: While nearly half of all people with Alzheimer's disease (AD) have
      agitation symptoms every month, little is known about the costs of agitation in
      AD. We calculated the monetary costs associated with agitation in older adults
      with AD in the UK from a National Health Service and personal social services
      perspective. DESIGN: Prospective cohort study. SETTING: London and the South East
      Region of the UK (LASER-AD study). PARTICIPANTS: 224 people with AD recruited
      between July 2002 and January 2003 and followed up for 54 months. PRIMARY AND
      SECONDARY OUTCOME MEASURES: The primary outcome was health and social care costs,
      including accommodation costs and costs of contacts with health and social care
      services. Agitation was assessed using the Neuropsychiatric Inventory (NPI)
      agitation score. RESULTS: After adjustment, health and social care costs varied
      significantly by agitation, from L29,000 over a 1 year period with no agitation
      symptoms (NPI agitation score=0) to L57,000 at the most severe levels of
      agitation (NPI agitation score=12; p=0.01). The mean excess cost associated with
      agitation per person with AD was L4091 a year, accounting for 12% of the health
      and social care costs of AD in our data, and equating to L2 billion a year across
      all people with AD in the UK. CONCLUSIONS: Agitation in people with AD represents
      a substantial monetary burden over and above the costs associated with cognitive
      impairment.

PMID- 25770237
TI  - Polychlorinated biphenyl quinone induces endothelial barrier dysregulation by
      setting the cross talk between VE-cadherin, focal adhesion, and MAPK signaling.
AB  - Environmental hazardous material polychlorinated biphenyl (PCB) exposure is
      associated with vascular endothelial dysfunction, which may increase the risk of
      cardiovascular diseases and cancer metastasis. Our previous studies illustrated
      the cytotoxic, antiproliferative, and genotoxic effects of a synthetic, quinone
      type, highly reactive metabolite of PCB, 2,3,5-trichloro-6-phenyl
      [1,4]benzoquinone (PCB29-pQ). Here, we used it as the model compound to
      investigate its effects on vascular endothelial integrity and permeability. We
      demonstrated that noncytotoxic doses of PCB29-pQ induced vascular endothelial
      (VE)-cadherin junction disassembly by increasing the phosphorylation of VE
      cadherin at Y658. We also found that focal adhesion assembly was required for
      PCB29-pQ-induced junction breakdown. Focal adhesion site-associated actin stress
      fibers may serve as holding points for cytoskeletal tension to regulate the
      cellular contractility. PCB29-pQ exposure promoted the association of actin
      stress fibers with paxillin-containing focal adhesion sites and enlarged the
      size/number of focal adhesions. In addition, PCB29-pQ treatment induced
      phosphorylation of paxillin at Y118. By using pharmacological inhibition, we
      further demonstrated that p38 activation was necessary for paxillin
      phosphorylation, whereas extracellular signal-regulated kinases-1/2 activation
      regulated VE-cadherin phosphorylation. In conclusion, these results indicated
      that PCB29-pQ stimulates endothelial hyperpermeability by mediating VE-cadherin
      disassembly, junction breakdown, and focal adhesion formation. Intervention
      strategies targeting focal adhesion and MAPK signaling could be used as
      therapeutic approaches for preventing adverse cardiovascular health effects
      induced by environmental toxicants such as PCBs. 

PMID- 25770238
TI  - Angiotensin II type I receptor blockade attenuates reflex cutaneous
      vasoconstriction in aged but not young skin.
AB  - Stimulation of angiotensin II type I receptors (AT1R) elicits vasoconstriction
      (VC) that may be occurring through the activation of a pathogenic vascular
      pathway such as Rho kinase (ROCK). We hypothesize that reflex cutaneous VC to
      whole body cooling (mean skin temperature = 30.5 degrees C) in older humans
      relies in part on AT1R activation, which may explain greater ROCK activity
      attendant with aging. Two microdialysis (MD) fibers were placed in the forearm
      skin of 10 young (Y; 24 +/- 1 yr) and 10 older (O; 70 +/- 2 yr) individuals for
      infusion of 1) lactated Ringer's solution (switched to fasudil, a ROCK
      antagonist, after cooling); and 2) AT1R blockade with losartan. Laser Doppler
      flux (LDF) was measured over each MD site and cutaneous vascular conductance
      (CVC) was calculated (CVC = LDF/mean arterial pressure) and expressed as percent
      change from baseline (%DeltaCVCBASELINE). In older individuals the VC response to
      whole body cooling was blunted (Y = -34 +/- 2, O = -17 +/- 3%DeltaCVC) and was
      further attenuated at the losartan site (Y = -34 +/- 3, O = -9 +/- 3%DeltaCVC; P
      < 0.05). The VC response to an exogenous 10-MUM dose of angiotensin II (Y = -27
      +/- 3, O = -42 +/- 5%DeltaCVC) was completely blocked in sites pretreated with
      losartan or with fasudil. These data suggest that AT1R activation contributes to
      the reflex VC response in aged but not young skin. Furthermore, the angiotensin
      II component of the VC response appears to occur primarily through a ROCK
      mediated mechanism. 

PMID- 25770239
TI  - Racing to the flatline: heart rate and beta-adrenergic stimulation quicken the
      pace.

PMID- 25770240
TI  - Regulating PPARdelta signaling as a potential therapeutic strategy for skeletal
      muscle disorders in heart failure.

PMID- 25770242
TI  - Pressure dependency of aortic pulse wave velocity in vivo is not affected by
      vasoactive substances that alter aortic wall tension ex vivo.
AB  - Aortic stiffness, a predictive parameter in cardiovascular medicine, is blood
      pressure dependent and experimentally requires isobaric measurement for
      meaningful comparison. Vasoactive drug administration to change peripheral
      resistance and blood pressure allows such isobaric comparison but may alter large
      conduit artery wall tension, directly changing aortic stiffness. This study
      quantifies effects of sodium nitroprusside (SNP, vasodilator) and phenylephrine
      (PE, vasoconstrictor) on aortic stiffness measured by aortic pulse wave velocity
      (aPWV) assessed by invasive pressure catheterization in anaesthetized Sprague
      Dawley rats (n = 7). This was compared with nondrug-dependent alteration of blood
      pressure through reduced venous return induced by partial vena cava occlusion. In
      vivo drug concentration was estimated by modeling clearance rates. Ex vivo
      responses of excised thoracic and abdominal aortic rings to drugs was measured
      using myography. SNP administration did not alter aPWV compared with venous
      occlusion (P = 0.21-0.87). There was a 5% difference in aPWV with PE
      administration compared with venous occlusion (P < 0.05). The estimated in vivo
      maximum concentration of PE (7.0 +/- 1.8 *10(-7) M) and SNP (4.2 +/- 0.6 *10(-7)
      M) caused ex vivo equivalent contraction of 52 mmHg (thoracic) and 112 mmHg
      (abdominal) and relaxation of 96% (both abdominal and thoracic), respectively,
      despite having a negligible effect on aPWV in vivo. This study demonstrates that
      vasoactive drugs administered to alter systemic blood pressure have a negligible
      effect on aPWV and provide a useful tool to study pressure-normalized and
      pressure-dependent aPWV in large conduit arteries in vivo. However, similar drug
      concentrations affect aortic ring wall tension ex vivo. Future studies
      investigating in vivo and ex vivo kinetics will need to elucidate mechanisms for
      this marked difference. 

PMID- 25770241
TI  - Fibrosis worsens chronic lymphedema in rodent tissues.
AB  - Secondary lymphedema in humans is a common consequence of lymph node dissection
      (LND) to treat breast cancer. A peculiar characteristic of the disease is that
      lifelong swelling often precipitously appears several years after the surgical
      treatment, often due to an inflammatory stimulus. Although the incidence of
      secondary lymphedema dramatically increases after radiation therapy, the
      relationship between fibrotic scarring and the eventual appearance of lymphedema
      remains unclear. To clarify the role of fibrosis in secondary lymphedema
      initiation, we chemically increased fibrosis in rodent tissues with bleomycin and
      assessed the ability of the local lymphatic system to prevent lymphedema, either
      acutely or in a chronic state induced by inflammation. We found that bleomycin
      injections exacerbated fibrotic matrix deposition in an acute mouse tail
      lymphedema model (P < 0.005), reduced wound closure (P < 0.005), and impaired the
      ability of tail lymphatics to regenerate (P < 0.005) and reduce the swelling (P <
      0.05). When fibrosis was worsened with bleomycin after axillary LND in the rat
      foreleg, the ability of the foreleg lymphatic system to reduce the chronic state
      swelling induced by stimulated inflammation was severely impaired (P < 0.005).
      Indocyanine green lymphography in axillary LND-recovered rat forelegs revealed a
      worsened lymphatic drainage due to inflammation and bleomycin pretreatment.
      Although inflammation reduced the drainage of dextran fluid tracer from control
      forelegs (P < 0.05), the reduction in fluid drainage was more severe after
      axillary LND when fibrosis was first increased (P < 0.005). These findings
      demonstrate that fibrosis reduces the lymphatic capacity to functionally
      regenerate and prevent the chronic appearance of lymphedema. 

PMID- 25770243
TI  - Impaired cardiac mitochondrial oxidative phosphorylation and enhanced
      mitochondrial oxidative stress in feline hypertrophic cardiomyopathy.
AB  - Mitochondrial dysfunction and oxidative stress are important players in the
      development of various cardiovascular diseases, but their roles in hypertrophic
      cardiomyopathy (HCM) remain unknown. We examined whether mitochondrial oxidative
      phosphorylation (OXPHOS) capacity was impaired with enhanced mitochondrial
      oxidative stress in HCM. Cardiac and skeletal muscles were obtained from 9
      domestic cats with spontaneously occurring HCM with preserved left ventricular
      systolic function and from 15 age-matched control cats. Mitochondrial OXPHOS
      capacities with nonfatty acid and fatty acid substrates in permeabilized fibers
      and isolated mitochondria were assessed using high-resolution respirometry. ROS
      release originating from isolated mitochondria was assessed by
      spectrofluorometry. Thiobarbituric acid-reactive substances were also measured as
      a marker of oxidative damage. Mitochondrial ADP-stimulated state 3 respiration
      with complex I-linked nonfatty acid substrates and with fatty acid substrates,
      respectively, was significantly lower in the hearts of HCM cats compared with
      control cats. Mitochondrial ROS release during state 3 with complex I-linked
      substrates and thiobarbituric acid-reactive substances in the heart were
      significantly increased in cats with HCM. In contrast, there were no significant
      differences in mitochondrial OXPHOS capacity, mitochondrial ROS release, and
      oxidative damage in skeletal muscle between groups. Mitochondrial OXPHOS capacity
      with both nonfatty acid substrates and fatty acid substrates was impaired with
      increased mitochondrial ROS release in the feline HCM heart. These findings
      provide new insights into the pathophysiology of HCM and support the hypothesis
      that restoration of the redox state in the mitochondria is beneficial in the
      treatment of HCM. 

PMID- 25770244
TI  - Nestin upregulation characterizes vascular remodeling secondary to hypertension
      in the rat.
AB  - Proliferation and hypertrophy of vascular smooth muscle cells represent hallmark
      features of vessel remodeling secondary to hypertension. The intermediate
      filament protein nestin was recently identified in vascular smooth muscle cells
      and in other cell types directly participated in proliferation. The present study
      tested the hypothesis that vessel remodeling secondary to hypertension was
      characterized by nestin upregulation in vascular smooth muscle cells. Two weeks
      after suprarenal abdominal aorta constriction of adult male Sprague-Dawley rats,
      elevated mean arterial pressure increased the media area and thickness of the
      carotid artery and aorta and concomitantly upregulated nestin protein levels. In
      the normal adult rat carotid artery, nestin immunoreactivity was observed in a
      subpopulation of vascular smooth muscle cells, and the density significantly
      increased following suprarenal abdominal aorta constriction. Filamentous nestin
      was detected in cultured rat carotid artery- and aorta-derived vascular smooth
      muscle cells and an analogous paradigm observed in human aorta-derived vascular
      smooth muscle cells. ANG II and EGF treatment of vascular smooth muscle cells
      stimulated DNA and protein synthesis and increased nestin protein levels.
      Lentiviral short-hairpin RNA-mediated nestin depletion of carotid artery-derived
      vascular smooth muscle cells inhibited peptide growth factor-stimulated DNA
      synthesis, whereas protein synthesis remained intact. These data have
      demonstrated that vessel remodeling secondary to hypertension was characterized
      in part by nestin upregulation in vascular smooth muscle cells. The selective
      role of nestin in peptide growth factor-stimulated DNA synthesis has revealed
      that the proliferative and hypertrophic responses of vascular smooth muscle cells
      were mediated by divergent signaling events. 

PMID- 25770246
TI  - Eukaryotic elongation factor 2 kinase mediates monocrotaline-induced pulmonary
      arterial hypertension via reactive oxygen species-dependent vascular remodeling.
AB  - Pulmonary arterial (PA) hypertension (PAH) is a progressive and lethal disease
      that is caused by increased vascular contractile reactivity and structural
      remodeling. These changes contribute to increasing pulmonary peripheral vascular
      resistance, finally leading to right heart failure and death. Eukaryotic
      elongation factor 2 kinase (eEF2K) is a Ca(2+)/calmodulin-dependent protein
      kinase. We previously revealed that eEF2K protein increases in the mesenteric
      artery from spontaneously hypertensive rats and partly mediates the development
      of hypertension via a promotion of ROS-dependent vascular inflammatory responses
      and proliferation and migration of vascular smooth muscle cells. However, a role
      of eEF2K in the pathogenesis of PAH is unknown. In the present study, we tested
      the hypothesis that eEF2K may be involved in the pathogenesis of PAH. PAH was
      induced by a single intraperitoneal injection of monocrotaline (MCT; 60 mg/kg) to
      rats. A specific eEF2K inhibitor, A-484954 (2.5 mg.kg(-1).day(-1)), was
      intraperitoneally injected for 14 days. Long-term A-484954 treatment inhibited
      MCT-induced increased PA pressure. It was revealed that A-484954 inhibited MCT
      induced PA hypertrophy and fibrosis but not impairment of endothelium-dependent
      and -independent relaxation. Furthermore, A-484954 inhibited MCT-induced NADPH
      oxidase-1 expression and ROS generation as well as matrix metalloproteinase-2
      activation. In conclusion, the present results suggest that eEF2K at least partly
      mediates MCT-induced PAH via stimulation of vascular structural remodeling
      perhaps through NADPH oxidase-1/ROS/matrix metalloproteinase-2 pathway. 

PMID- 25770245
TI  - Effect of a myosin regulatory light chain mutation K104E on actin-myosin
      interactions.
AB  - Familial hypertrophic cardiomyopathy (FHC) is the most common cause of sudden
      cardiac death in young individuals. Molecular mechanisms underlying this disorder
      are largely unknown; this study aims at revealing how disruptions in actin-myosin
      interactions can play a role in this disorder. Cross-bridge (XB) kinetics and the
      degree of order were examined in contracting myofibrils from the ex vivo left
      ventricles of transgenic (Tg) mice expressing FHC regulatory light chain (RLC)
      mutation K104E. Because the degree of order and the kinetics are best studied
      when an individual XB makes a significant contribution to the overall signal, the
      number of observed XBs in an ex vivo ventricle was minimized to ~20.
      Autofluorescence and photobleaching were minimized by labeling the myosin lever
      arm with a relatively long-lived red-emitting dye containing a chromophore system
      encapsulated in a cyclic macromolecule. Mutated XBs were significantly better
      ordered during steady-state contraction and during rigor, but the mutation had no
      effect on the degree of order in relaxed myofibrils. The K104E mutation increased
      the rate of XB binding to thin filaments and the rate of execution of the power
      stroke. The stopped-flow experiments revealed a significantly faster observed
      dissociation rate in Tg-K104E vs. Tg-wild-type (WT) myosin and a smaller second
      order ATP-binding rate for the K104E compared with WT myosin. Collectively, our
      data indicate that the mutation-induced changes in the interaction of myosin with
      actin during the contraction-relaxation cycle may contribute to altered
      contractility and the development of FHC. 

PMID- 25770247
TI  - Restraint stress exacerbates cardiac and adipose tissue pathology via beta
      adrenergic signaling in rats with metabolic syndrome.
AB  - Restraint stress stimulates sympathetic nerve activity and can affect adiposity
      and metabolism. However, the effects of restraint stress on cardiovascular and
      metabolic disorders in metabolic syndrome (MetS) have remained unclear. We
      investigated the effects of chronic restraint stress and beta-adrenergic receptor
      (beta-AR) blockade on cardiac and adipose tissue pathology and metabolic
      disorders in a rat model of MetS. DahlS.Z-Lepr(fa)/Lepr(fa) (DS/obese) rats,
      derived from a cross between Dahl salt-sensitive and Zucker rats. Rats were
      exposed to restraint stress (restraint cage, 2 h/day) for 4 wk from 9 wk of age
      with or without daily subcutaneous administration of the beta-AR blocker
      propranolol (2 mg/kg). Age-matched homozygous lean littermates of DS/obese rats
      (DahlS.Z-Lepr(+)/Lepr(+) rats) served as control animals. Chronic restraint
      stress exacerbated hypertension as well as left ventricular hypertrophy,
      fibrosis, diastolic dysfunction, and oxidative stress in a manner sensitive to
      propranolol treatment. Restraint stress attenuated body weight gain in DS/obese
      rats, and this effect tended to be reversed by propranolol (P = 0.0682).
      Restraint stress or propranolol did not affect visceral or subcutaneous fat mass.
      However, restraint stress potentiated cardiac and visceral adipose tissue
      inflammation in DS/obese rats, and these effects were ameliorated by propranolol.
      Restraint stress also exacerbated glucose intolerance, insulin resistance, and
      abnormal lipid metabolism in a manner sensitive to propranolol. In addition,
      restraint stress increased urinary norepinephrine excretion, and propranolol
      attenuated this effect. Our results thus implicate beta-ARs in the exacerbation
      of cardiac and adipose tissue pathology and abnormal glucose and lipid metabolism
      induced by restraint stress in this model of MetS. 

PMID- 25770248
TI  - Patient-specific finite element analysis of ascending aorta aneurysms.
AB  - Catastrophic ascending aorta aneurysm (AsAA) dissection and rupture can be
      prevented by elective surgical repair, but identifying individuals at risk
      remains a challenge. Typically the decision to operate is based primarily on the
      overall aneurysm size, which may not be a reliable indicator of risk. In this
      study, AsAA inflation and rupture was simulated in 27 patient-specific finite
      element models constructed from clinical CT imaging data and tissue mechanical
      testing data from matching patients. These patients included n = 8 with
      concomitant bicuspid aortic valve (BAV), n = 10 with bovine aortic arch (BAA),
      and n = 10 with neither BAV nor BAA. AsAA rupture risk was found to increase with
      elevated systolic wall stress and tissue stiffness. The aortic size index was
      sufficient for identifying the patients with the lowest risk of rupture, but
      unsuitable for delineating between patients at moderate and high risk. There was
      no correlation between BAV or BAA and AsAA rupture risk; however, the AsAA
      morphology was different among these patients. These results support the use of
      mechanical parameters such as vessel wall stress and tissue stiffness for AsAA
      presurgical evaluation. 

PMID- 25770249
TI  - Application of three-dimensional speckle tracking echocardiography to assess left
      ventricular regional work using wall tension-regional area loop.
AB  - Three-dimensional (3-D) speckle tracking echocardiography allows us to track a
      change in regional endocardial surface area. The change of regional area during a
      cardiac cycle should be useful for assessing left ventricular regional work. We
      investigated the feasibility of assessing regional work, calculated as the area
      within the wall tension-regional area (T-A) loop using 3-D echocardiography.
      Three-dimensional full-volume images were acquired using 3-D echocardiography
      (Artida, Toshiba) at baseline and during brief occlusion of the left circumflex
      coronary artery in eight dogs. Wall tension was calculated according to Laplace's
      law for a spherical model. Area change ratio (in %) determined by area tracking
      was transformed into a change of regional area (in cm(2)) by a custom software.
      We calculated the area within the T-A loop (TAA) in the area under transient
      ischemia (risk area) and the remote area as regional work and validated the T-A
      loop method by comparing the global integral of TAA with the total work assessed
      by the pressure-volume loop. During coronary occlusion, regional work for the
      risk area significantly decreased (baseline vs. occlusion, 26.8 +/- 10.7 vs. 18.4
      +/- 7.8 mmHg.cm(3); P < 0.05), whereas that for the remote area did not change.
      The global integral of TAA closely correlated with the total work assessed by the
      pressure-volume loop (r = 0.91, P < 0.0001). The wall T-A loop reflected regional
      dysfunction caused by myocardial ischemia. This analysis using 3-D speckle
      tracking echocardiography might be useful to quantify left ventricular regional
      work. 

PMID- 25770250
TI  - Thirty years of treating HIV-1 infection: where next?

PMID- 25770251
TI  - Prevalence and risk factors of soil-transmitted helminth infection in Nepal.

PMID- 25770252
TI  - BCG-associated heterologous immunity, a historical perspective: intervention
      studies in animal models of infectious diseases.

PMID- 25770253
TI  - Thiamin deficiency in people with obesity.
AB  - Although obesity has been viewed traditionally as a disease of excess nutrition,
      evidence suggests that it may also be a disease of malnutrition. Specifically,
      thiamin deficiency was found in 15.5-29% of obese patients seeking bariatric
      surgery. It can present with vague signs and symptoms and is often overlooked in
      patients without alcohol use disorders. This review explores the relatively new
      discovery of high rates of thiamin deficiency in certain populations of people
      with obesity, including the effects of thiamin deficiency and potential
      underlying mechanisms of deficiency in people with obesity. The 2 observational
      studies that examined the prevalence in preoperative bariatric surgery patients
      and gaps in our current knowledge (including the prevalence of thiamin deficiency
      in the general obese population and whether the current RDA for thiamin meets the
      metabolic needs of overweight or obese adults) are reviewed. Suggestions for
      future areas of research are included. 

PMID- 25770254
TI  - Dietary patterns, cognitive decline, and dementia: a systematic review.
AB  - Nutrition is an important modifiable risk factor that plays a role in the
      strategy to prevent or delay the onset of dementia. Research on nutritional
      effects has until now mainly focused on the role of individual nutrients and
      bioactive components. However, the evidence for combined effects, such as
      multinutrient approaches, or a healthy dietary pattern, such as the Mediterranean
      diet, is growing. These approaches incorporate the complexity of the diet and
      possible interaction and synergy between nutrients. Over the past few years,
      dietary patterns have increasingly been investigated to better understand the
      link between diet, cognitive decline, and dementia. In this systematic review we
      provide an overview of the literature on human studies up to May 2014 that
      examined the role of dietary patterns (derived both a priori as well as a
      posteriori) in relation to cognitive decline or dementia. The results suggest
      that better adherence to a Mediterranean diet is associated with less cognitive
      decline, dementia, or Alzheimer disease, as shown by 4 of 6 cross-sectional
      studies, 6 of 12 longitudinal studies, 1 trial, and 3 meta-analyses. Other
      healthy dietary patterns, derived both a priori (e.g., Healthy Diet Indicator,
      Healthy Eating Index, and Program National Nutrition Sante guideline score) and a
      posteriori (e.g., factor analysis, cluster analysis, and reduced rank
      regression), were shown to be associated with reduced cognitive decline and/or a
      reduced risk of dementia as shown by all 6 cross-sectional studies and 6 of 8
      longitudinal studies. More conclusive evidence is needed to reach more targeted
      and detailed guidelines to prevent or postpone cognitive decline. 

PMID- 25770255
TI  - The significance of duration and amount of sodium reduction intervention in
      normotensive and hypertensive individuals: a meta-analysis.
AB  - The purpose of this meta-analysis was to establish the time for achievement of
      maximal blood pressure (BP) efficacy of a sodium reduction (SR) intervention and
      the relation between the amount of SR and the BP response in individuals with
      hypertension and normal BP. Relevant studies were retrieved from a pool of 167
      randomized controlled trials (RCTs) published in the period 1973-2010 and
      integrated in meta-analyses. Fifteen relevant RCTs were included in the maximal
      efficacy analysis. After initiation of sodium reduction (range: 55-118 mmol/d),
      there were no significant differences in systolic blood pressure (SBP) or
      diastolic blood pressure (DBP) between measurements at weeks 1 and 2 (?SBP: -0.18
      mmHg/?DBP: 0.12 mmHg), weeks 1 and 4 (?SBP: -0.50 mmHg/?DBP: 0.35 mmHg), weeks 2
      and 4 (?SBP: -0.20 mmHg/?DBP: -0.10 mmHg), weeks 2 and 6 (?SBP: -0.50 mmHg/?DBP: 
      0.42 mmHg), and weeks 4 and 6 (?SBP: 0.39 mmHg/?DBP: -0.22 mmHg). Eight relevant
      RCTs were included in the dose-response analysis, which showed that within the
      established usual range of sodium intake [<248 mmol/d (5700 mg/d)], there was no
      relation between the amount of SR (range: 136-188 mmol) and BP outcome in
      normotensive populations [?SBP: 0.99 mm Hg (95% CI: -2.12, 4.10 mm Hg),
      [corrected] P = 0.53; ?DBP: -0.49 mm Hg (95% CI: -4.0, 3.03), P = 0.79]. In
      contrast, prehypertensive and hypertensive populations showed a significant dose
      response relation (range of sodium reduction: 77-140 mmol/d) [?SBP: 6.87 mmHg
      (95% CI: 5.61, 8.12, P < 0.00001); ?DBP: 3.61 mmHg (95% CI: 2.83, 4.39, P <
      0.00001)]. Consequently, the importance of kinetic and dynamic properties of
      sodium reduction, as well as baseline BP, should probably be considered when
      establishing a policy of sodium reduction.

PMID- 25770256
TI  - A systematic review of controlled trials of lower-protein or energy-containing
      infant formulas for use by healthy full-term infants.
AB  - Infant formulas have historically been developed based on providing
      macronutrients at intake concentrations approximately matching the composition of
      human milk. In most countries, targets of 1.4-1.5 g of protein/dL and 20 kcal/oz
      (67-68 kcal/dL) have been set as the protein and energy concentrations for
      formulas during the first year of life, although this may be an overestimation of
      these contents. Recent introduction of lower-protein and -energy formulas in full
      term infants led us to systematically review the literature for its effects on
      growth. Following the Preferred Reporting Items for Systematic Reviews and Meta
      Analysis guidelines, our inclusion criteria were studies that enrolled healthy
      full-term infants and evaluated lower-protein or lower-energy formula, reported
      anthropometric outcomes including weight and length, and followed infants for at
      least 6 mo. Six studies were eligible for inclusion. These studies varied in the
      content of nutrients provided in the intervention and control groups, by
      additional dietary components in the study groups, and the timing and length of
      the intervention, which limit their usefulness for interpreting newly introduced
      lower-protein and -energy formulas in the United States. These studies suggest
      adequate growth during infancy and early childhood with infant formulas with
      concentrations of protein and energy slightly below historical standards in the
      United States. Further long-term research is needed to assess the impact of the
      use of lower-protein and/or lower-energy products, especially for nutritionally
      at-risk populations such as preterm infants and infants who are born small for
      gestational age. 

PMID- 25770257
TI  - Diosgenin, 4-hydroxyisoleucine, and fiber from fenugreek: mechanisms of actions
      and potential effects on metabolic syndrome.
AB  - Metabolic syndrome and its complications continue to rise in prevalence and show
      no signs of abating in the immediate future. Therefore, the search for effective
      treatments is a high priority in biomedical research. Products derived from
      botanicals have a time-honored history of use in the treatment of metabolic
      diseases including type 2 diabetes. Trigonella foenum-graecum, commonly known as
      fenugreek, is an annual herbaceous plant that has been a staple of traditional
      herbal medicine in many cultures. Although fenugreek has been studied in both
      clinical and basic research settings, questions remain about its efficacy and
      biologic mechanisms of action. Diosgenin, 4-hydroxyisoleucine, and the fiber
      component of the plant are the most intensively studied bioactive constituents
      present in fenugreek. These compounds have been demonstrated to exert beneficial
      effects on several physiologic markers including glucose tolerance, inflammation,
      insulin action, liver function, blood lipids, and cardiovascular health. Although
      insights into the molecular mechanisms underlying the favorable effects of
      fenugreek have been gained, we still do not have definitive evidence establishing
      its role as a therapeutic agent in metabolic disease. This review aims to
      summarize the currently available evidence on the physiologic effects of the 3
      best-characterized bioactive compounds of fenugreek, with particular emphasis on
      biologic mechanisms of action relevant in the context of metabolic syndrome. 

PMID- 25770258
TI  - Role of resistant starch in improving gut health, adiposity, and insulin
      resistance.
AB  - The realization that low-glycemic index diets were formulated using resistant
      starch led to more than a decade of research on the health effects of resistant
      starch. Determination of the metabolizable energy of the resistant starch product
      allowed for the performance of isocaloric studies. Fermentation of resistant
      starch in rodent studies results in what appears to be a healthier gut,
      demonstrated by increased amounts of short-chain fatty acids, an apparent
      positive change in the microbiota, and increased gene expression for gene
      products involved in normal healthy proliferation and apoptosis of potential
      cancer cells. Additionally, consumption of resistant starch was associated with
      reduced abdominal fat and improved insulin sensitivity. Increased serum glucagon
      like peptide 1 (GLP-1) likely plays a role in promoting these health benefits.
      One rodent study that did not use isocaloric diets demonstrated that the use of
      resistant starch at 8% of the weight of the diet reduced body fat. This appears
      to be approximately equivalent to the human fiber requirement. In human subjects,
      insulin sensitivity is increased with the feeding of resistant starch. However,
      only 1 of several studies reports an increase in serum GLP-1 associated with
      resistant starch added to the diet. This means that other mechanisms, such as
      increased intestinal gluconeogenesis or increased adiponectin, may be involved in
      the promotion of improved insulin sensitivity. Future research may confirm that
      there will be improved health if human individuals consume the requirement for
      dietary fiber and a large amount of the fiber is fermentable. 

PMID- 25770259
TI  - Microbial degradation of whole-grain complex carbohydrates and impact on short
      chain fatty acids and health.
AB  - Whole-grain cereals have a complex dietary fiber (DF) composition consisting of
      oligosaccharides (mostly fructans), resistant starch, and nonstarch
      polysaccharides (NSPs); the most important are arabinoxylans, mixed-linkage
      beta(1,3; 1,4)-d-glucan (beta-glucan), and cellulose and the noncarbohydrate
      polyphenolic ether lignin. The highest concentration of NSPs and lignin is found
      in the outer cell layers of the grain, and refined flour will consequently be
      depleted of a large proportion of insoluble DF components. The flow and
      composition of carbohydrates to the large intestine are directly related to the
      intake of DF. The type and composition of cereal DF can consequently be used to
      modulate the microbial composition and activity as well as the production and
      molar ratios of short-chain fatty acids (SCFAs). Arabinoxylans and beta-glucan in
      whole-grain cereals and cereal ingredients have been shown to augment SCFA
      production, with the strongest relative effect on butyrate. When arabinoxylans
      were provided as a concentrate, the effect was only on total SCFA production.
      Increased SCFA production in the large intestine was shown by the concentration
      in the portal vein, whereas the impact on the concentration in peripheral blood
      was less because the majority of propionate and butyrate is cleared in the liver.
      Active microbial fermentation with increased SCFA production reduced the exposure
      of potentially toxic compounds to the epithelium, potentially stimulating
      anorectic hormones and acting as signaling molecules between the gut and the
      peripheral tissues. The latter can have implications for insulin sensitivity and
      glucose homeostasis. 

PMID- 25770261
TI  - Zinc.

PMID- 25770260
TI  - Nutrition targeting by food timing: time-related dietary approaches to combat
      obesity and metabolic syndrome.
AB  - Effective nutritional guidelines for reducing abdominal obesity and metabolic
      syndrome are urgently needed. Over the years, many different dietary regimens
      have been studied as possible treatment alternatives. The efficacy of low-calorie
      diets, diets with different proportions of fat, protein, and carbohydrates,
      traditional healthy eating patterns, and evidence-based dietary approaches were
      evaluated. Reviewing literature published in the last 5 y reveals that these
      diets may improve risk factors associated with obesity and metabolic syndrome.
      However, each diet has limitations ranging from high dropout rates to maintenance
      difficulties. In addition, most of these dietary regimens have the ability to
      attenuate some, but not all, of the components involved in this complicated
      multifactorial condition. Recently, interest has arisen in the time of day foods
      are consumed (food timing). Studies have examined the implications of eating at
      the right or wrong time, restricting eating hours, time allocation for meals, and
      timing of macronutrient consumption during the day. In this paper we review new
      insights into well-known dietary therapies as well as innovative time-associated
      dietary approaches for treating obesity and metabolic syndrome. We discuss
      results from systematic meta-analyses, clinical interventions, and animal models.

PMID- 25770262
TI  - Lino M. Expenditures on children by families, 2013. Washington, DC: US Department
      of Agriculture, Center for Nutrition Policy and Promotion; 2014. Miscellaneous
      Publication No. 1528-2013.

PMID- 25770263
TI  - Implausible data, false memories, and the status quo in dietary assessment.

PMID- 25770264
TI  - Reply to E Archer and SN Blair.

PMID- 25770273
TI  - Crime, punishment, and the American criminal justice system.

PMID- 25770266
TI  - Squeezing fact from fiction about 100% fruit juice.
AB  - Total fruit intake in the United States is ~1 cup equivalent per day, or one-half
      of the 2010 Dietary Guidelines for Americans recommendation for adults. Two
      thirds of the fruit consumed is whole fruit and one-third is 100% juice. The
      nutritional value of whole fruit, with the exception of fiber and vitamin C, may
      be retained with appropriate juice production methods and storage conditions. One
      hundred percent fruit juice consumption is associated with a number of health
      benefits, such as improved cardiovascular health and decreased obesity, although
      some of these and other potential benefits are controversial. Comprehensive
      analyses of the evidence by the Academy of Nutrition and Dietetics in 2014, the
      US Dietary Guidelines Advisory Committee in 2010, and the Australian Dietary
      Guidelines of 2013 concluded that 100% fruit juice is not related to adiposity in
      children when consumed in appropriate amounts for age and energy needs. However,
      some reports suggest the consumption of fruit juice contributes to unhealthful
      outcomes, particularly among children. A dietary modeling study on the best ways
      to meet the fruit intake shortfall showed that a combination of whole fruit and
      100% juice improved dietary density of potassium and vitamin C without
      significantly increasing total calories. Notably, 100% juice intake was capped at
      amounts consistent with the 2001 American Pediatric Association guidance. The
      preponderance of evidence supports the position that 100% fruit juice delivers
      essential nutrients and phytonutrients, provides year-round access to a variety
      of fruits, and is a cost-effective way to help people meet fruit recommendations.

PMID- 25770274
TI  - Dialectical principlism: an approach to finding the most ethical action.
AB  - Most forensic psychiatrists occasionally face complex situations in forensic work
      in which ethics dilemmas cause discomfort. They want to determine the most
      ethical action, but the best choice is unclear. Fostering justice is primary in
      forensic roles, but secondary duties such as traditional biomedical ethics and
      personal values like helping society, combating racism, and being sensitive to
      cultural issues can impinge on or even outweigh the presumptive primary duty in
      extreme cases. Similarly, in treatment the psychiatrists' primary duty is to
      patients, but that can be outweighed by secondary duties such as protecting
      children and the elderly or maintaining security. The implications of one's
      actions matter. In forensic work, if the psychiatrist determines that he should
      not assist the party who wants to hire him, despite evidence clearly supporting
      its side, the only ethical option becomes not to accept the case at all, because
      the evidence does not support the better side. Sometimes it can be ethical to
      accept cases only for one side. In ethics-related dilemmas, I call the method of
      prioritizing and balancing all types of conflicting principles, duties, and
      personal and societal values in a dialectic to resolve conflicts among them
      dialectical principlism. This approach is designed to help determine the most
      ethical action. It is aspirational and is not intended to get the psychiatrist
      into trouble. 

PMID- 25770275
TI  - John H. Wigmore on the abolition of partisan experts.
AB  - The American justice system traditionally has relied on expert witnesses hired by
      adverse parties, resulting in the appearance of dueling hired guns. There have
      been attempts to reform the system through court-appointed impartial experts, but
      trial attorneys have resisted them. Celebrated cases have brought the problem to
      the forefront--for example, the 1924 murder trial of Richard Loeb and Nathan
      Leopold, Jr, in Chicago. These young men were on trial for kidnapping and killing
      a teenage boy. That there was no motive but thrill-seeking incensed citizens, who
      called for their death. Several psychiatrists testified at the penalty phase. The
      judge sentenced the defendants to life in prison, ostensibly because of their
      age. Commenting on the case, John H. Wigmore, Dean of Northwestern Law School and
      authority on evidence, critiqued the system of partisan experts. This article
      contains a reprint of his editorial and a discussion of it in the context of
      evolving expert testimony standards. My conclusion is that a robust but honest
      airing of opinions is most helpful in criminal cases and that court-appointed
      experts may be more appropriate in civil and domestic relations matters.

PMID- 25770276
TI  - Commentary: is the plot thickening for partisan forensic expert witnesses?
AB  - Knowledge of the past has a powerful way of clarifying the challenges of the
      present. Dr. Weiss enables the reader to exploit this phenomenon as it applies to
      the important perennial struggle of the expert witness for objectivity. 

PMID- 25770277
TI  - Approaches to involuntary admission of the mentally ill in the People's Republic
      of China: changes in legislation from 2002 to 2012.
AB  - A systematic analysis of laws on involuntary commitment of mentally ill
      individuals in China has never been undertaken. In this article, we explore the
      trajectory of the legislation and discuss the social and cultural factors
      underlying the changes in the laws. In this description and analysis of the
      differences and similarities in the current legal framework and procedures for
      involuntary commitment of the mentally ill across the mental health regulations
      of seven localities and the National Mental Health Law, one can see a gradual
      trend toward more stringent legislation during the past 10 years. The
      compromises, reversals, and circuitous course of the legislative process reflect
      the difficulties that the government faced in achieving a balance between
      benefits to society and the individual as it attempted to revamp the delivery of
      mental health services. The 2012 National Mental Health Law, despite some
      weaknesses, is an important step toward standardizing the diverse practices in
      involuntary admission of mentally ill persons in China. Further research on the
      influence of the National Law on mental health services is clearly needed. 

PMID- 25770278
TI  - Commentary: a comparative review of involuntary admission of people with mental
      illness in China and Barbados.
AB  - Shao and Xie discuss the changes to involuntary admission laws across seven
      jurisdictions in China over a 10-year period and the influences on the new
      National Act. The discussion is important, given allegations of human rights
      abuses in that country. Strengths and weaknesses of the National Act are raised
      and compared with our local experience on the island of Barbados. Further
      discussion of the most appropriate approaches to involuntary admission would be
      useful. 

PMID- 25770279
TI  - Commentary: civil commitment and its reform.
AB  - Internationally, civil commitment laws have gone through substantial reforms in
      the past 50 years. Discernible shifts from the medically paternalistic to the
      excessively legalistic may be giving way to a blending of legislative intent
      under the rubric of therapeutic jurisprudence. In the light of those
      international movements, Shao and Xie describe how China's new mental health law
      shows the impact of these international and local influences on the development
      and practice of mental health law in China. The new Law was passed in 2012. It
      sets a broad vision for mental health services and mental health promotion in
      Chinese society as well as providing the legal framework for civil commitment.
      Practicalities of implementation may be highly significant in the success of the
      legislation. 

PMID- 25770280
TI  - Gender and the experience of mental health expert witness testimony.
AB  - Mental health expert witness testimony involves complex tasks, and the capacity
      to perform under pressure is a fundamental skill of a forensic professional. In
      this context, it is important to understand the nuances of the provision of
      expert witness testimony. There have been several efforts to examine gender bias
      across legal and medical systems. Despite these reviews, little is known about
      how men and women differ or are similar with regard to performing expert witness
      functions. The purpose of this pilot study was to examine whether the testimony
      experiences of psychiatry and psychology experts vary by gender. Differences
      across certain domains, such as the sense of never experiencing anxiety and the
      sense of one's impact on case outcome were seen across genders. Few other gender
      based differences in the experience of providing expert witness testimony were
      seen. Although the findings of this study raise further questions, they highlight
      some of the important subtleties noted in forensic practice and the work of the
      expert witness. In future studies, researchers should continue to explore these
      findings on the influence of gender and expand to consider culture and race as
      additional factors in the experience of expert witness testimony. As forensic
      professional practice evolves, it is important to understand unique aspects of
      forensic practice, to improve training of forensic experts, and to assist
      forensic experts in anticipating what they may experience related to the
      provision of expert testimony. 

PMID- 25770281
TI  - Gender bias and judicial decisions of undue influence in testamentary challenges.
AB  - Allegations of undue influence constitute a common basis for contests of wills.
      Legal research from the 1990s suggests that gender bias factors significantly
      into judicial decision-making regarding alleged undue influence and testamentary
      intent. In this study, we sought to assess whether this bias is present today and
      to identify any factors that may be associated with it. Probate judges from
      several jurisdictions in the United States were asked to consider two
      hypothetical case vignettes drawn from actual published decisions. In our study,
      the gender of the testator played only a minor role in how judges weighed factors
      in the decision-making process and, overall, did not significantly influence
      opinions regarding the presence of undue influence. The specifics of the case and
      the gender of the judge emerged as the most consistent and robust potential
      influences on decision-making. Our results suggest that probate rulings involving
      undue influence are likely to represent a complex interaction of factors
      involving the testator's and judge's genders and the specifics of individual
      cases. The implications of these findings are discussed. 

PMID- 25770282
TI  - Differences in expert witness knowledge: do mock jurors notice and does it
      matter?
AB  - The knowledge of experts presumably affects their credibility and the degree to
      which the trier of fact agrees with them. However, specific effects of
      demonstrated knowledge are largely unknown. In this experiment, we manipulated a
      forensic expert's level of knowledge in a mock-trial paradigm. We tested the
      influence of low versus high expert knowledge on mock juror perceptions of expert
      credibility, on agreement with the expert, and on sentencing. We also tested
      expert gender as a potential moderator. Knowledge effects were statistically
      significant; however, these differences carried little practical utility in
      predicting mock jurors' ultimate decisions. Contrary to the hypotheses that high
      knowledge would yield increased credibility and agreement, knowledge
      manipulations influenced only perceived expert likeability. The low-knowledge
      expert was perceived as more likeable than the high-knowledge counterpart, a
      paradoxical finding. No significant differences across expert gender were found.
      Implications for conceptualizing expert witness knowledge and credibility and
      their potential effects on juror decision-making are discussed. 

PMID- 25770283
TI  - The prevalence of delusional disorder in prison.
AB  - Delusional disorder has important implications for forensic psychiatrists, as
      delusions are not infrequently related to criminal behavior. Thus, we
      hypothesized that delusional disorder is over-represented in correctional
      populations. We conducted a retrospective chart review of the electronic medical
      records from 2000 to 2012 of New Jersey Department of Corrections inmates who
      remained incarcerated as of March 2012. Potential cases of delusional disorder
      were initially identified by using a search for current or past diagnoses of such
      disorders or other diagnoses that could be misdiagnosed cases. After an initial
      chart review identified an inmate as having probable delusional disorder
      according to Diagnostic and Statistical Manual of Mental Disorders, Fourth
      Edition, Text Revision (DSM-IV-TR) criteria, the diagnosis was confirmed by at
      least one concurring independent review. We estimate a point prevalence of 0.24
      percent for delusional disorder in our population, which is eight times higher
      than that expected in the community. 

PMID- 25770284
TI  - Updates since Brown v. Plata: alternative solutions for prison overcrowding in
      California.
AB  - With the number of inmates under the care of the California Department of
      Corrections and Rehabilitation (CDCR) swelling over the past few decades,
      California faces a challenge. The U.S. Supreme Court ruled in their 2011 decision
      in Brown v. Plata that overcrowding violates inmates' Eighth Amendment rights,
      specifically that they are denied adequate medical and mental health care.
      Federally mandated release programs have historically raised some concerns
      regarding public safety and fiscal efficiency. Given the large number of mentally
      ill inmates in the United States, alternatives such as assisted outpatient
      treatment, mental health courts, and increased funding for substance use
      treatment can be used proactively to reduce the CDCR population and provide long
      term solutions to the overcrowding problem. These alternatives have already shown
      long-term cost savings in addition to reducing the recidivism of individuals
      involved and would help provide appropriate diversion for mentally ill
      individuals. 

PMID- 25770285
TI  - From group data to useful probabilities: the relevance of actuarial risk
      assessment in individual instances.
AB  - Probability plays a ubiquitous role in decision-making through a process in which
      we use data from groups of past outcomes to make inferences about new situations.
      Yet in recent years, many forensic mental health professionals have become
      persuaded that overly wide confidence intervals render actuarial risk assessment
      instruments virtually useless in individual assessments. If this were true, the
      mathematical properties of probabilistic judgments would preclude forensic
      clinicians from applying group-based findings about risk to individuals. As a
      consequence, actuarially based risk estimates might be barred from use in legal
      proceedings. Using a fictional scenario, I seek to show how group data have an
      obvious application to individual decisions. I also explain how misunderstanding
      the aims of risk assessment has led to mistakes about how, when, and why group
      data apply to individual instances. Although actuarially based statements about
      individuals' risk have many pitfalls, confidence intervals pose no barrier to
      using actuarial tools derived from group data to improve decision-making about
      individual instances. 

PMID- 25770286
TI  - Adaptation.

PMID- 25770290
TI  - Coordinate loss of MAP3K7 and CHD1 promotes aggressive prostate cancer.
AB  - Prostate cancer subtypes are poorly defined and functional validation of drivers
      of ETS rearrangement-negative prostate cancer has not been conducted. Here, we
      identified an ETS(-) subtype of aggressive prostate cancer (ERG(
      )MAP3K7(del)CHD1(del)) and used a novel developmental model and a cell line
      xenograft model to show that cosuppression of MAP3K7 and CHD1 expression promotes
      aggressive disease. Analyses of publicly available prostate cancer datasets
      revealed that MAP3K7 and CHD1 were significantly codeleted in 10% to 20% of
      localized tumors and combined loss correlated with poor disease-free survival. To
      evaluate the functional impact of dual MAP3K7-CHD1 loss, we suppressed Map3k7
      and/or Chd1 expression in mouse prostate epithelial progenitor/stem cells
      (PrP/SC) and performed tissue recombination experiments in vivo. Dual shMap3k7
      shChd1 PrP/SC recombinants displayed massive glandular atypia with regions of
      prostatic intraepithelial neoplasia and carcinoma apparent. Combined Map3k7-Chd1
      suppression greatly disrupted normal prostatic lineage differentiation; dual
      recombinants displayed significant androgen receptor loss, increased
      neuroendocrine differentiation, and increased neural differentiation. Clinical
      samples with dual MAP3K7-CHD1 loss also displayed neuroendocrine and neural
      characteristics. In addition, dual Map3k7-Chd1 suppression promoted E-cadherin
      loss and mucin production in recombinants. MAP3K7 and CHD1 protein loss also
      correlated with Gleason grade and E-cadherin loss in clinical samples. To further
      validate the phenotype observed in the PrP/SC model, we suppressed MAP3K7 and/or
      CHD1 expression in LNCaP prostate cancer cells. Dual shMAP3K7-shCHD1 LNCaP
      xenografts displayed increased tumor growth and decreased survival compared with
      shControl, shMAP3K7, and shCHD1 xenografts. Collectively, these data identify
      coordinate loss of MAP3K7 and CHD1 as a unique driver of aggressive prostate
      cancer development.

PMID- 25770292
TI  - CCR 20th anniversary commentary: BMS-247550-microtubule stabilization as
      successful targeted therapy.
AB  - In a landmark article published in the May 1, 2001, issue of Clinical Cancer
      Research, Lee and colleagues reported the original preclinical studies
      demonstrating anticancer activity of BMS-247550 (ixabepilone) against taxane
      sensitive and taxane-resistant cancers. Subsequent clinical trials established
      the clinical efficacy of ixabepilone, leading to its regulatory approval for the
      treatment of drug-resistant metastatic or locally advanced breast cancers.

PMID- 25770293
TI  - Translational implications of tumor heterogeneity.
AB  - Advances in next-generation sequencing and bioinformatics have led to an
      unprecedented view of the cancer genome and its evolution. Genomic studies have
      demonstrated the complex and heterogeneous clonal landscape of tumors of
      different origins and the potential impact of intratumor heterogeneity on
      treatment response and resistance, cancer progression, and the risk of disease
      relapse. However, the significance of subclonal mutations, in particular
      mutations in driver genes, and their evolution through time and their dynamics in
      response to cancer therapies, is yet to be determined. The necessary tools are
      now available to prospectively determine whether clonal heterogeneity can be used
      as a biomarker of clinical outcome and to what extent subclonal somatic
      alterations might influence clinical outcome. Studies that use longitudinal
      tissue sampling, integrating both genomic and clinical data, have the potential
      to reveal the subclonal composition and track the evolution of tumors to address
      these questions and to begin to define the breadth of genetic diversity in
      different tumor types and its relevance to patient outcome. Such studies may
      provide further evidence for drug-resistance mechanisms informing combinatorial,
      adaptive, and tumor immune therapies placed within the context of tumor
      evolution.

PMID- 25770295
TI  - Pharmacogenomic modeling in pancreatic cancer-letter.

PMID- 25770294
TI  - Phase I study of a bispecific ligand-directed toxin targeting CD22 and CD19
      (DT2219) for refractory B-cell malignancies.
AB  - PURPOSE: The novel bispecific ligand-directed toxin (BLT) DT2219 consists of a
      recombinant fusion between the catalytic and translocation enhancing domain of
      diphtheria toxin (DT) and bispecific single-chain variable fragments (scFV) of
      antibodies targeting human CD19 and CD22. We conducted a phase I dose-escalation
      study to assess the safety, maximum tolerated dose, and preliminary efficacy of
      DT2219 in patients with relapsed/refractory B-cell lymphoma or leukemia.
      EXPERIMENTAL DESIGN: DT2219 was administered intravenously over 2 hours every
      other day for 4 total doses. Dose was escalated from 0.5 MUg/kg/day to 80
      MUg/kg/day in nine dose cohorts until a dose-limiting toxicity (DLT) was
      observed. RESULTS: Twenty-five patients with mature or precursor B-cell lymphoid
      malignancies expressing CD19 and/or CD22 enrolled to the study. Patients received
      median 3 prior lines of chemotherapy and 8 failed hematopoietic transplantation.
      All patients received a single course of DT2219; one patient was retreated. The
      most common adverse events, including weight gain, low albumin, transaminitis,
      and fever were transient grade 1-2 and occurred in patients in higher dose
      cohorts (>=40 MUg/kg/day). Two subjects experienced DLT at dose levels 40 and 60
      MUg/kg. Durable objective responses occurred in 2 patients; one was complete
      remission after 2 cycles. Correlative studies showed a surprisingly low incidence
      of neutralizing antibody (30%). CONCLUSIONS: We have determined the safety of a
      novel immunotoxin DT2219 and established its biologically active dose between 40
      and 80 MUg/kg/day *4. A phase II study exploring repetitive courses of DT2219 is
      planned.

PMID- 25770296
TI  - Pharmacogenomic modeling in pancreatic cancer-response.

PMID- 25770297
TI  - Correction: Silencing of human phosphatidylethanolamine-binding protein 4
      sensitizes breast cancer cells to tumor necrosis factor-alpha-induced apoptosis
      and cell growth arrest.

PMID- 25770298
TI  - Correction: TP53 mutation spectrum in breast cancer is subtype specific and has
      distinct prognostic relevance.

PMID- 25770300
TI  - Metastasis-associated protein 1 drives tumor cell migration and invasion through
      transcriptional repression of RING finger protein 144A.

PMID- 25770301
TI  - Insights into the inhibitory mechanisms of the regulatory protein IIAGlc on
      melibiose permease activity.

PMID- 25770302
TI  - 14-3-3 interacts directly with and negatively regulates pro-apoptotic Bax.

PMID- 25770303
TI  - Phosphorylation of p27Kip1 on serine 10 is required for its binding to CRM1 and
      nuclear export.

PMID- 25770304
TI  - Citation analysis of Acta Dermatovenerologica Alpina, Pannonica et Adriatica:
      1992-2013.
AB  - Acta Dermatovenerologica Alpina, Pannonica et Adriatica is the leading journal in
      the field of dermatology and sexually transmitted infections in the region.
      Several important steps were taken during the last 20 years to improve the
      journal's quality, global visibility, and international impact. Since 1992, 699
      bibliographical items have been published, which received 1,360 citations. Web of
      Science citable items received on average 2.29 citations per item. Importantly,
      almost half (49.6%) of all citations retrieved to date were received from 2012
      onwards. The predicted impact factor was calculated in a way to match official
      impact factors published annually in Thomson Scientific Journal Citation Reports.
      Citation analysis shows a substantial increase of the predicted impact factor
      since 2006, with values above 0.5 since 2007. For the first time in the journal's
      history, a predicted impact factor value above 1.0 was recorded in 2013. 

PMID- 25770305
TI  - Treatment of vulvovaginal candidiasis: a review of the literature.
AB  - Vulvovaginal candidiasis (VVC) affects around three-quarters of all women during
      their reproductive age, although the exact incidence of VVC is difficult to
      determine because many patients are self-treated. The infections are divided into
      complicated and uncomplicated. Uncomplicated VVC is most effectively treated with
      local azoles. Oral treatment with a single dose of fluconazole is also effective
      for treating uncomplicated VVC. Treatment of complicated VVC is prolonged and
      most commonly consists of multiple doses of oral fluconazole or at least 1 week
      of local azoles. The role of probiotics in treating VVC is still disputed. This
      article presents a review of the literature on the various treatment options for
      VVC. Treatment for the most common pathogens that cause complicated VVC is also
      discussed. 

PMID- 25770306
TI  - Trichomoniasis: a brief review of diagnostic methods and our experience with real
      time PCR for detecting infection.
AB  - Trichomoniasis is the most common non-viral sexually transmitted infection, and
      it is caused by the protozoan flagellate Trichomonas vaginalis. Although highly
      prevalent in sexually active women, it has long been overlooked in other groups
      of potentially infected people. Recently, studies have shown that trichomoniasis
      increases the risk of infection with human immunodeficiency virus and can cause
      adverse outcomes of pregnancy, which has increased interest in T. vaginalis and
      increased the need for highly sensitive diagnostic tests. This article summarizes
      the diagnostic methods most commonly used in the diagnosis of trichomoniasis,
      including the most sensitive and specific nucleic acid amplification tests. It
      also presents the results of our study comparing the performance of wet mount
      microscopy and culture to real-time PCR for detecting the parasite. 

PMID- 25770307
TI  - Connubial ecthyma gangrenosum in a healthy couple: a consort counterpart of a
      "kissing ulcer".
AB  - Ecthyma gangrenosum is a relatively rare cutaneous infection generally thought to
      be linked to sepsis or bacteremia caused by Pseudomonas aeruginosa in severely
      ill or otherwise immunocompromised patients. Here we report on a healthy middle
      aged couple with a typical ecthyma gangrenosum lesion on their thighs, obviously
      caused by spreading through intimate contact between two skin surfaces: a sort of
      "consort kissing ulcer." Although they declined to allow microbiological
      sampling, the lesions gradually but completely regressed with oral ciprofloxacin
      treatment, leaving atrophic scars. 

PMID- 25770308
TI  - Faun tail: a rare cutaneous sign of spinal dysraphism.
AB  - Faun tail is a triangle-shaped hypertrichosis of the lumbosacral region. It is a
      rare condition and it can be a cutaneous marker of underlying spinal cord
      anomaly. We report on a 17-year-old female patient with hypertrichosis on the
      lumbosacral area since birth that was later diagnosed with tethered cord in
      magnetic resonance imaging. 

PMID- 25770309
TI  - Invasive mucinous carcinoma arising in ectopic axillary breast tissue: a case
      report and literature review.
AB  - BACKGROUND: Invasive mucinous carcinoma arising in ectopic axillary breast tissue
      is an uncommon diagnosis. While some published medical literature makes
      recommendations regarding the management of ectopic primaries, many of these
      recommendations are outdated. We therefore hope to provide general guidance with
      the management of this rare entity. CASE REPORT: We report a case of a 70-year
      old woman with primary invasive mucinous carcinoma of ectopic breast tissue. A
      literature study was performed on primary ectopic breast carcinoma. This case
      report with review of the literature was performed to provide rationales for a
      more conservative treatment based upon current data and treatment paradigms.
      Although the diagnosis of primary ectopic breast carcinoma is uncommon, the
      presence of a suspicious nodule along the mammary ridge should alert the
      clinician to consider the possibility of this diagnosis. A mammogram and
      ultrasound of the nodule were performed and the suspicious nodule was biopsied,
      confirming the diagnosis. Breast conservation was performed with standard nodal
      evaluation. CONCLUSIONS: The management of primary ectopic breast carcinoma
      should be based upon current breast conservation techniques of orthotopic breast
      cancer. Current data suggest that standard treatment paradigms remain applicable
      to this rare clinical entity.

PMID- 25770310
TI  - Impact of repetitive transcranial magnetic stimulation on post-stroke dysmnesia
      and the role of BDNF Val66Met SNP.
AB  - BACKGROUND: Little is known about the effects of low-frequency repetitive
      transcranial magnetic stimulation (rTMS) on dysmnesia and the impact of brain
      nucleotide neurotrophic factor (BDNF) Val66Met single-nucleotide polymorphism
      (SNP). This study investigated the impact of low-frequency rTMS on post-stroke
      dysmnesia and the impact of BDNF Val66Met SNP. MATERIAL AND METHODS: Forty
      patients with post-stroke dysmnesia were prospectively randomized into the rTMS
      and sham groups. BDNF Val66Met SNP was determined using restriction fragment
      length polymorphism. Montreal Cognitive Assessment (MoCA), Loewenstein
      Occupational Therapy of Cognitive Assessment (LOTCA), and Rivermead Behavior
      Memory Test (RBMT) scores, as well as plasma BDNF concentrations, were measured
      at baseline and at 3 days and 2 months post-treatment. RESULTS: MoCA, LOTCA, and
      RBMT scores were higher after rTMS. Three days after treatment, BDNF decreased in
      the rTMS group but it increased in the sham group (P<0.05). Two months after
      treatment, RMBT scores in the rTMS group were higher than in the sham group, but
      not MoCA and LOTCA scores. CONCLUSIONS: Low-frequency rTMS may improve after
      stoke memory through various pathways, which may involve polymorphisms and
      several neural genes, but not through an increase in BDNF levels.

PMID- 25770311
TI  - Interventions to increase the use of electronic health information by healthcare
      practitioners to improve clinical practice and patient outcomes.
AB  - BACKGROUND: There is a large volume of health information available, and, if
      applied in clinical practice, may contribute to effective patient care. Despite
      an abundance of information, sub-optimal care is common. Many factors influence
      practitioners' use of health information, and format (electronic or other) may be
      one such factor. OBJECTIVES: To assess the effects of interventions aimed at
      improving or increasing healthcare practitioners' use of electronic health
      information (EHI) on professional practice and patient outcomes. SEARCH METHODS:
      We searched The Cochrane Library (Wiley), MEDLINE (Ovid), EMBASE (Ovid), CINAHL
      (EBSCO), and LISA (EBSCO) up to November 2013. We contacted researchers in the
      field and scanned reference lists of relevant articles. SELECTION CRITERIA: We
      included studies that evaluated the effects of interventions to improve or
      increase the use of EHI by healthcare practitioners on professional practice and
      patient outcomes. We defined EHI as information accessed on a computer. We
      defined 'use' as logging into EHI. We considered any healthcare practitioner
      involved in patient care. We included randomized, non-randomized, and cluster
      randomized controlled trials (RCTs, NRCTs, CRCTs), controlled clinical trials
      (CCTs), interrupted time series (ITS), and controlled before-and-after studies
      (CBAs).The comparisons were: electronic versus printed health information; EHI on
      different electronic devices (e.g. desktop, laptop or tablet computers, etc.;
      cell / mobile phones); EHI via different user interfaces; EHI provided with or
      without an educational or training component; and EHI compared to no other type
      or source of information. DATA COLLECTION AND ANALYSIS: Two review authors
      independently extracted data and assessed the risk of bias for each study. We
      used GRADE to assess the quality of the included studies. We reassessed
      previously excluded studies following our decision to define logins to EHI as a
      measure of professional behavior. We reported results in natural units. When
      possible, we calculated and reported median effect size (odds ratio (OR),
      interquartile ranges (IQR)). Due to high heterogeneity across studies, meta
      analysis was not feasible. MAIN RESULTS: We included two RCTs and four CRCTs
      involving 352 physicians, 48 residents, and 135 allied health practitioners.
      Overall risk of bias was low as was quality of the evidence. One comparison was
      supported by three studies and three comparisons were supported by single
      studies, but outcomes across the three studies were highly heterogeneous. We
      found no studies to support EHI versus no alternative. Given these factors, it
      was not possible to determine the relative effectiveness of interventions. All
      studies reported practitioner use of EHI, two reported on compliance with
      electronic practice guidelines, and none reported on patient outcomes.One trial
      (139 participants) measured guideline adherence for an electronic versus printed
      guideline, but reported no difference between groups (median OR 0.85, IQR 0.74 to
      1.08). One small cross-over trial (10 participants) reported increased use of
      clinical guidelines when provided with a mobile versus stationary, desktop
      computer (mean use per shift: intervention group (IG) 3.6, standard deviation
      (SD) 1.7 vs. control group (CG) 2.0 (SD 1.9), P value = 0.033). One cross-over
      trial (203 participants) reported that using a customized versus a generic
      interface had little impact on practitioners' use of EHI (mean difference in
      adjusted end-of-study rate: 0.77 logins/month/user, 95% confidence interval (CI)
      CI 0.43 to 1.11). Three trials included education or training and reported
      increased use of EHI by practitioners following training. AUTHORS' CONCLUSIONS:
      This review provided no evidence that the use of EHI translates into improved
      clinical practice or patient outcomes, though it does suggest that when
      practitioners are provided with EHI and education or training, the use of EHI
      increases. We have defined use as the activity of logging into an EHI resource,
      but based on our findings use does not automatically translate to the application
      of EHI in practice. While using EHI may be an important component of evidence
      based medicine, alone it is insufficient to improve patient care or clinical
      practices. For EHI to be applied in patient care, it will be necessary to
      understand why practitioners' are reluctant to apply EHI when treating people,
      and to determine the most effective way(s) to reduce this reluctance.

PMID- 25770312
TI  - Emotion Regulation Feeding Practices Link Parents' Emotional Eating to Children's
      Emotional Eating: A Moderated Mediation Study.
AB  - Past research suggests an association between parents' and children's emotional
      eating, but research has yet to examine mechanisms underlying this association.
      OBJECTIVE: The current study examined whether feeding for emotion regulation
      mediates the association between parents' and children's emotional eating, and
      whether this association is moderated by children's self-regulation in eating.
      METHOD: 95 parents reported on their own and their children's emotional eating,
      their children's self-regulation in eating, as well as their feeding practices.
      RESULTS: Findings revealed that feeding for emotion regulation mediated the
      association between parents' and children's emotional eating when children's self
      regulation in eating was low, but not when self-regulation in eating was high.
      CONCLUSION: The current findings demonstrate the complexity of the link between
      parents' and children's emotional eating, suggesting practitioners should
      consider both feeding practices and children's self-regulation in eating when
      designing intervention programs.

PMID- 25770313
TI  - LBIBCell: a cell-based simulation environment for morphogenetic problems.
AB  - MOTIVATION: The simulation of morphogenetic problems requires the simultaneous
      and coupled simulation of signalling and tissue dynamics. A cellular resolution
      of the tissue domain is important to adequately describe the impact of cell-based
      events, such as cell division, cell-cell interactions and spatially restricted
      signalling events. A tightly coupled cell-based mechano-regulatory simulation
      tool is therefore required. RESULTS: We developed an open-source software
      framework for morphogenetic problems. The environment offers core functionalities
      for the tissue and signalling models. In addition, the software offers great
      flexibility to add custom extensions and biologically motivated processes. Cells
      are represented as highly resolved, massless elastic polygons; the viscous
      properties of the tissue are modelled by a Newtonian fluid. The Immersed Boundary
      method is used to model the interaction between the viscous and elastic
      properties of the cells, thus extending on the IBCell model. The fluid and
      signalling processes are solved using the Lattice Boltzmann method. As
      application examples we simulate signalling-dependent tissue dynamics.
      AVAILABILITY AND IMPLEMENTATION: The documentation and source code are available
      on http://tanakas.bitbucket.org/lbibcell/index.html

PMID- 25770314
TI  - Oral anticoagulation, aspirin, or no therapy in patients with nonvalvular AF with
      0 or 1 stroke risk factor based on the CHA2DS2-VASc score.
AB  - BACKGROUND: Even a single additional stroke risk factor in patients with atrial
      fibrillation may confer a risk of stroke. However, there is no consensus on how
      best to treat these patients. OBJECTIVES: Our objective was to investigate the
      risk of stroke and bleeding and the impact of antithrombotic therapy among low
      risk patients, i.e., with 0 or 1 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 risk factor.
      METHODS: The nationwide cohort for this study was established by linking data
      from the Danish Civil Registration System, the Danish National Patient Register,
      and the Danish National Prescription Registry. We studied 39,400 patients
      discharged with incident nonvalvular atrial fibrillation with 0 or 1 CHA2DS2-VASc
      risk factor; 23,572 were not treated, 5,353 were initiated on aspirin, and 10,475
      were initiated on warfarin. RESULTS: Stroke event rates for untreated low-risk
      patients (CHA2DS2-VASc = 0 [male], 1 [female]) were 0.49 per 100 person-years at
      1 year and 0.47 per 100 person-years at full follow-up (intention-to-treat).
      Bleeding event rates among untreated low-risk patients were 1.08 per 100 person
      years at 1 year and 0.97 at full follow-up. The presence of 1 additional stroke
      risk factor (CHA2DS2-VASc = 1 [male], = 2 [female]) among untreated patients
      increased the stroke rate at 1 year to 1.55 per 100 person-years, representing a
      significant 3.01-fold increase. At the 1-year follow-up, bleeding increased 2.35
      fold, and death increased 3.12-fold. CONCLUSIONS: Low-risk patients (CHA2DS2-VASc
      = 0 [male], 1 [female]) have a truly low risk for stroke and bleeding. With 1
      additional stroke risk factor (CHA2DS2-VASc = 1 [male], = 2 [female]), there was
      a significant increase in event rates (particularly mortality) if
      nonanticoagulated.

PMID- 25770316
TI  - Patients with atrial fibrillation and a CHA2DS2-VASc score of 1: are they at low
      or high stroke risk?

PMID- 25770315
TI  - Effect of naturally random allocation to lower low-density lipoprotein
      cholesterol on the risk of coronary heart disease mediated by polymorphisms in
      NPC1L1, HMGCR, or both: a 2 * 2 factorial Mendelian randomization study.
AB  - BACKGROUND: Considerable uncertainty exists as to whether lowering low-density
      lipoprotein cholesterol (LDL-C) by inhibiting the Niemann-Pick C1-Like 1 (NPC1L1)
      receptor with ezetimibe, either alone or in combination with a 3-hydroxy-3
      methylglutaryl-coenzyme A reductase (HMGCR) inhibitor (statin), will reduce the
      risk of coronary heart disease (CHD). OBJECTIVES: This study evaluated the effect
      of naturally random allocation to lower LDL-C mediated by polymorphisms in the
      NPC1L1 gene (target of ezetimibe), the HMGCR gene (target of statins), or both
      (target of combination therapy) on the risk of CHD. METHODS: We constructed
      NPC1L1 and HMGCR genetic LDL-C scores to naturally randomize participants into 4
      groups: reference, lower LDL-C mediated by NPC1L1 polymorphisms, lower LDL-C
      mediated by HMGCR polymorphisms, or lower LDL-C mediated by polymorphisms in both
      NPC1L1 and HMGCR. We compared the risk of CHD (fatal or nonfatal myocardial
      infarction) among each group using a 2 * 2 factorial mendelian randomization
      study design. RESULTS: A total of 108,376 persons (10,464 CHD events) from 14
      studies were included. There were no significant differences in baseline
      characteristics among the 4 groups, thus confirming that allocation was random.
      Compared to the reference group, the NPC1L1 group had 2.4 mg/dl lower LDL-C and
      4.8% lower risk of CHD (odds ratio [OR]: 0.952, 95% confidence interval [CI]:
      0.920 to 0.985); whereas the HMGCR group had 2.9 mg/dl lower LDL-C and a similar
      5.3% lower risk of CHD (OR: 0.947, 95% CI: 0.909 to 0.986). The group with lower
      LDL-C mediated by both NPC1L1 and HMGCR polymorphisms had 5.8 mg/dl additively
      lower LDL-C and a 10.8% log-linearly additive lower risk of CHD (OR: 0.892, 95%
      CI: 0.854 to 0.932). CONCLUSIONS: The effect of lower LDL-C on the risk of CHD
      mediated by polymorphisms in NPC1L1, HMGCR, or both is approximately the same per
      unit lower LDL-C and log-linearly proportional to the absolute exposure to lower
      LDL-C.

PMID- 25770317
TI  - Eicosapentaenoic acid in cancer improves body composition and modulates
      metabolism.
AB  - OBJECTIVES: The objective of this review article is to present the most recent
      intervention studies with EPA on nutritional outcomes in cancer patients, e.g.
      nutritional status, weight & lean body mass. METHODS: For this purpose a
      PubMed((r)) and MedLine((r)) search of the published literature up to and
      including January 2014 that contained the keywords: cancer, sarcopenia, EPA,
      omega-3 fatty acids, weight, intervention trial, muscle mass was conducted. The
      collected data was summarized and written in text format and in tables that
      contained: study design, patient' population, sample size, statistical
      significance and results of the intervention. The paper will cover malignancy,
      body composition, intervention with EPA, physiological mechanisms of action of
      EPA, effect of EPA on weight and body composition, future research. RESULTS: In
      cancer patients deterioration of muscle mass can be present regardless of body
      weight or Body Mass Index (BMI). Thus, sarcopenia in cancer patients with
      excessive fat mass (FM), entitled sarcopenic obesity, has gained greater
      relevance in clinical practice; it can negatively influence patients' functional
      status, tolerance to treatments & disease prognosis. The search for an effective
      nutritional intervention that improves body composition (preservation of muscle
      mass and muscle quality) is of utmost importance for clinicians and patients. The
      improvement of muscle quality is an even more recent area of interest because it
      has probable implications in patients' prognosis. Eicosapentaenoic acid (EPA) has
      been identified as a promising nutrient with the wide clinical benefits. Several
      mechanisms have been proposed to explain EPA potential benefits on body
      composition: inhibition of catabolic stimuli by modulating pro-inflammatory
      cytokines production and enhancing insulin sensitivity that induces protein
      synthesis; also, EPA may attenuate deterioration of nutritional status resulting
      from antineoplastic therapies by improving calorie and protein intake as well.
      CONCLUSIONS: Indeed, cancer-related sarcopenia/cachexia is a multifactorial
      syndrome characterized by inflammation, anorexia, weight loss, and muscle/adipose
      tissue loss mediated by proinflammatory cytokines, e.g. TNF-alpha and IL-6,
      resulting in increased chemotherapy toxicity, costs, morbidity and mortality.
      With this review we found that EPA can reduce inflammation and has the potential
      to modulate nutritional status/body composition. In view of the modest survival
      benefits of chemotherapy/radiotherapy in some cancers, important issues for
      physicians are to optimize well-being, Quality of Life via nutritional status and
      adequate body composition. Thus, improvement in nutritional status is a central
      outcome.

PMID- 25770318
TI  - Antineoplastic effects of Chlorella pyrenoidosa in the breast cancer model.
AB  - OBJECTIVES: There has been considerable interest in both clinical and preclinical
      research about the role of phytochemicals in the reduction of risk for cancer in
      humans. The aim of this study was to determine the antineoplastic effects of
      Chlorella pyrenoidosa in experimental breast cancer in vivo and in vitro.
      METHODS: In this experiment, the antineoplastic effects of C. pyrenoidosa in the
      chemoprevention of N-methyl-N-nitrosourea-induced mammary carcinogenesis in
      female rats were evaluated. Chlorella powder was administered through diet at
      concentrations of 0.3% and 3%. The experiment was terminated 14 wk after
      carcinogen administration. At autopsy, mammary tumors were removed and prepared
      for histopathological and immunohistochemical analysis. In vitro cytotoxicity
      assay, parameters of apoptosis, and proliferation after chlorella treatment in
      human breast adenocarcinoma (MCF-7) cells were carried out. RESULTS: Basic
      parameters of experimental carcinogenesis, mechanism of action (biomarkers of
      apoptosis, proliferation, and angiogenesis), chosen metabolic variables, and side
      effects after long-term chlorella treatment in animals were assessed. Chlorella
      at higher concentration suppressed tumor frequency by 61% (P < 0.02) and
      lengthened tumor latency by 12.5 d (P < 0.02) in comparison with the controls.
      Immunohistochemical analysis of rat tumor cells showed caspase-7 expression
      increase by 73.5% (P < 0.001) and vascular endothelial growth factor receptor-2
      expression decrease by 19% (P = 0.07) after chlorella treatment. In a parallel in
      vitro study, chlorella significantly decreased survival of MCF-7 cells in a dose
      dependent manner. In chlorella-treated MCF-7 cells, a significant increase in
      cells having sub-G0/G1 DNA content and significant increase of early apoptotic
      and late apoptotic/necrotic cells after annexin V/PI staining assay were found.
      Decreases in mitochondrial membrane potential and increasing reactive oxygen
      species generation were observed in the chlorella-treated MCF-7 cells.
      CONCLUSIONS: This study is the first report on the antineoplastic effects of C.
      pyrenoidosa in experimental breast cancer in vivo and in vitro.

PMID- 25770320
TI  - Polyunsaturated fatty acids in cancer and their influence on biochemical and
      metabolic events and body composition.

PMID- 25770319
TI  - Synergistic anti-tumor effects of melatonin and PUFAs from walnuts in a murine
      mammary adenocarcinoma model.
AB  - OBJECTIVE: The aim of this study was to determine the effects of some
      polyunsaturated fatty acids plus phytomelatonin from walnuts in the development
      of mammary gland adenocarcinoma. METHODS: BALB/c mice were fed a semisynthetic
      diet supplemented with either 6% walnut oil and 8% walnut flour containing
      phytomelatonin (walnut diet: WD); or 6% corn oil plus commercial melatonin
      (melatonin diet: MD), or the control group (CD), which received only 6% of corn
      oil. Membrane fatty acids of tumor cells (TCs) were analyzed by gas liquid
      chromatography, cyclooxygenase (COX) and lipoxygenase (LOX) derivatives, and
      plasma melatonin by high-performance liquid chromatography; apoptosis and tumor
      infiltrating lymphocytes by flow cytometry. RESULTS: TCs from the MD and WD mice
      showed significant decreases in linoleic acid compared with the CD group (P <
      0.05). Significantly lower levels of LOX-[13(S)-HODE] were found in TCs from the
      MD and WD group than in CD (P < 0.0001). COX-[12(S)-HHT] was lower and 12 LOX
      [12(S)-HETE] was higher in TCs from the MD group than form the WD and CD arms (P
      < 0.05). Plasma melatonin, apoptosis, tumor infiltration, and survival time were
      significantly lower in CD mice than in MD and WD mice (P < 0.05). CONCLUSIONS:
      This study shows that melatonin, along with polyunsaturated fatty acids, exerts a
      selective inhibition of some COX and LOX activities and has a synergistic anti
      tumor effect on a mammary gland adenocarcinoma model.

PMID- 25770321
TI  - Evidence-based nutritional support of the elderly cancer patient.
AB  - The papers included in this section represent the effort of the Task Force on
      Nutrition of the International Society of Geriatric Oncology to synthetize the
      evidence-based concepts on nutritional support of the elderly cancer patients. In
      the attempt of presenting a comprehensive overview of the topic, the panel
      included experts from different specialties: basic researchers, nutritionists,
      geriatricians, nurses, dieticians, gastroenterologists, oncologists. Cancer in
      elderly people is a growing problem. Not only in almost every country, the
      proportion of people aged over 60 years is growing faster than any other age
      group, but cancer per se is also a disease of old adult-elderly people, hence the
      oncologists face an increasing number of these patients both now and in the next
      years. The are several studies on nutrition of elderly subjects and many other on
      nutrition of cancer patients but relatively few specifically devoted to the
      nutritional support of the elderly cancer patients. However, the awareness that
      elderly subjects account for a high proportion of the mixed cancer patients
      population, in some way legitimates us to extend some conclusions of the
      literature also to the elderly cancer patients. Although the topics of this
      Experts' Consensus have been written by specialists in different areas of
      nutrition, the final message is addressed to the oncologists. Not only they
      should be more directly involved in the simplest steps of the nutritional care
      (recognition of the potential existence of a "nutritional risk" which can
      compromise the planned oncologic program, use of some oral supplements, etc.)
      but, as the true experts of the natural history of their cancer patient, they
      should also coordinate the process of the nutritional support, integrating this
      approach in the overall multidisciplinary cancer care. 

PMID- 25770322
TI  - The elderly patient with cancer: a holistic view.
AB  - The elderly cancer patient (ECP) population is a heterogeneous group, ranging
      from competent, active, and fit individuals to those who are frail and
      cognitively impaired. A continuum exists from an increased vulnerability to
      stressors that results from the usual decreases in physiologic reserves (=aging)
      to the deregulation of multiple physiologic systems (=frailty). The ability or
      inability of carrying out activities of daily living is both a cause and an
      effect of frailty and may exacerbate the clinical manifestations of
      comorbidities. Cachexia is one of the most important comorbid conditions in ECPs,
      which can directly impair their quality of life, their ability to tolerate tumor
      directed treatments, and their ability to respond to rehabilitation. Gait speed,
      handgrip strength, and cognitive tests along with simple laboratory tests to rule
      out the presence of increased inflammatory state and/or a particular hormonal
      deficiency may guide interventions and allow for monitoring of clinical outcomes
      over time. An organized social network, collaborative support from the team of
      caregivers and sufficient home care services comprise a comprehensive care
      approach that guarantees successful treatment outcomes for the ECP population. 

PMID- 25770323
TI  - Why the oncologist should consider the nutritional status of the elderly cancer
      patient.
AB  - Epidemiologic studies show that malnutrition frequently afflicts elderly cancer
      patients. Malnutrition, (expressed as weight loss, or depletion of some body
      compartments or alteration of nutritional clinical or biochemical scores) is
      associated with higher morbidity/mortality, poor quality of life, reduced
      tolerance to oncologic therapy and poor efficacy of chemotherapy. Recently,
      sarcopenia, regardless of the presence of weight loss, has been identified as an
      independent risk factor for chemotherapy toxicity. 

PMID- 25770324
TI  - Which screening method is appropriate for older cancer patients at risk for
      malnutrition?
AB  - The risk for malnutrition increases with age and presence of cancer, and it is
      particularly common in older cancer patients. A range of simple and validated
      nutrition screening tools can be used to identify malnutrition risk in cancer
      patients (e.g., Malnutrition Screening Tool, Mini Nutritional Assessment Short
      Form Revised, Nutrition Risk Screening, and the Malnutrition Universal Screening
      Tool). Unintentional weight loss and current body mass index are common
      components of screening tools. Patients with cancer should be screened at
      diagnosis, on admission to hospitals or care homes, and during follow-up at
      outpatient or general practitioner clinics, at regular intervals depending on
      clinical status. Nutritional assessment is a comprehensive assessment of dietary
      intake, anthropometrics, and physical examination often conducted by dietitians
      or geriatricians after simple screening has identified at-risk patients. The
      result of nutritional screening, assessment and the associated care plans should
      be documented, and communicated, within and between care settings for best
      patient outcomes. 

PMID- 25770325
TI  - Nutritional support of the elderly cancer patient: the role of the nurse.
AB  - Cancer in the geriatric population is a growing problem. Malnutrition is common
      in cancer. A number of factors increase the risk for malnutrition in older people
      with cancer, including chronic comorbid conditions and normal physiological
      changes of aging. Nurses have an important role in the nutritional support of
      older cancer patients. To contribute to the improvement of nutritional support of
      these patients, nurses need appropriate training to be able to identify risk for
      malnutrition and offer a range of interventions tailored to individual need.
      Factors to consider in tailoring interventions include disease status, cancer
      site, cancer treatment, comorbidity, physiological age, method of facilitating
      dietary change, and family support. This article identifies ways in which nurses
      can contribute to the nutritional support of older cancer patients and thus help
      mitigate the effects of malnutrition. 

PMID- 25770326
TI  - Nutritional approaches in cancer: relevance of individualized counseling and
      supplementation.
AB  - Intensive individualized nutritional counseling requires nutrition professionals
      with specific experience in oncology. If the patient is unable to achieve his or
      her nutritional requirements via regular foods, nutritional supplements may be
      prescribed, the composition of which is based on detection of dietary deficits as
      well as a detailed intake questionnaire. Any nutritional intervention must be
      based on the need for an adequate intake and also must take into consideration
      other relevant factors such as digestive and absorptive capacity, the need for
      alleviation or arrest of symptoms, and any psychological issues. 

PMID- 25770328
TI  - Tube feeding in the elderly cancer patient.
AB  - In elderly cancer patients tube feeding, via a nasogastric tube or a
      (percutaneous) gastrostomy may be an efficient way of nutritionally supporting
      patients with extreme anorexia or dysphagia caused by a head&neck tumor or with
      an oro-pharyngeal-esophageal mucositis due to radiation therapy and/or
      chemotherapy. There is no definite difference, with regard to the clinical
      benefit, between nasogastric and gastrostomy feeding. Both procedures achieve
      good results in allowing the proper completion of the oncologic therapy. Whether
      to use a nasogastric tube or a (percutaneous) gastrostomy and whether to perform
      the procedure prophylactically or a la demande is a matter of controversy and
      depends more on the policy of the single institution and preferences of the
      patients than on evidence-based results. 

PMID- 25770327
TI  - Nutritional/metabolic response in older cancer patients.
AB  - The combination of age-related muscle loss (sarcopenia) and the diagnosis of
      cancer (and the onset of cachexia) is likely a metabolic challenge that skeletal
      muscle of older cancer patients is not prepared to handle. Albeit to a smaller
      extent than healthy older controls, the skeletal muscle of older cancer patients
      is still acutely anabolic to the provision of amino acids. To provide an anabolic
      stimulus to skeletal muscle during a time when it is susceptible to an advanced
      rate of breakdown due to cancer- and tumor-related factors, enhanced intake of
      protein and amino acid sources might be necessary and should likely be higher
      than the current US recommended daily intake of 0.8 g protein/kg body weight/day.
      Future studies should investigate whether the acute effects of amino acids on
      muscle protein anabolism can be sustained over a longer period of time in the
      presence of cancer cachexia in older patients. 

PMID- 25770329
TI  - Parenteral nutrition in the elderly cancer patient.
AB  - Parenteral nutrition may be considered when oral intake and/or enteral nutrition
      are not sufficient to maintain nutritional status and the patient is likely to
      die sooner from starvation than from the cancer. A detailed assessment should be
      made prior to the decision about whether parenteral nutrition should be started.
      A follow up plan should be documented with objective and patient centred
      treatment goals as well as specific time points for evaluation. 

PMID- 25770330
TI  - Tailoring the nutritional regimen in the elderly cancer patient.
AB  - Our knowledge of the macronutrient requirement of elderly cancer patient is still
      incomplete and mainly relies on studies of elderly (healthy) people and
      populations of cancer patients including both adult and elderly subjects.
      Patients with minor nutritional deterioration do not require any specific
      nutritional regimen, but cachectic patients do. Total energy expenditure can be
      unchanged or lower in advanced weight-losing patients (when compared with matched
      healthy controls) because the higher resting metabolic expenditure can be offset
      by reduced physical activity, and it approximates to 25-28 Kcal/kg/d. Protein
      requirement is probably 1.5 g amino acid (AA)/kg/d or more, especially if the
      goal is increased lean body mass. However, the final balance depends not only on
      the quantity of AA but also their quality: diets including a high percentage of
      essential AA and especially of branched-chain ones and leucine in particular, are
      advocated. Total fluid load should be prudent, around 25-30 ml/kg/d. 

PMID- 25770331
TI  - Nutritional support at the end of life.
AB  - For patients with cancer at the end of life the goal of nutritional care is to
      optimize quality of life and comfort. Food and drink should be served as
      requested by the patient but without exerting pressure. For patients who have
      developed cachexia and are potentially candidates to receive artificial
      nutrition, discussions between the patient, family and health care team are
      needed to set the goals of nutritional care, considering both the risk of adverse
      effects of the treatment and ethical issues. The premise for a benefit from
      parenteral nutrition is that survival of the tumor spread exceeds that of
      starvation (usually by about 2-3 months). 

PMID- 25770332
TI  - Nutritional support of the elderly cancer patient: long-term nutritional support.
AB  - Elderly cancer patients account for a growing part of home artificial nutrition
      patients. Long-term enteral or parenteral nutrition in the older patient with
      cancer is prescribed for sequels after treatment (dysphagia, intestinal failure)
      or for bowel obstruction. Home artificial nutrition should benefit from a
      specialized follow-up. For patients out of therapy, the goal of nutritional care
      is to optimize quality of life and comfort. 

PMID- 25770333
TI  - The oncologist as coordinator of the nutritional approach.
AB  - Although the nutritional approach, especially when delivered through a gastric or
      jejunal tube or in a central vein, is handled by the nutritional support team or
      a specialist in nutrition, it is the responsibility of the oncologist, who knows
      the natural history of the disease and the impact of the oncologic therapy, to
      identify the potential candidates for the nutritional support, to recommend the
      nutritional strategy and to integrate it within the oncologic program. If
      gastrointestinal function is preserved, the initial nutritional approach should
      be through oral supplementation, followed by tube feeding if previous attempts
      are unsuccessful or upper gastrointestinal tract is not accessible. Parenteral
      nutrition is the obligatory resort when patients are (sub)obstructed but it may
      also be a practical way to integrate an insufficient oral nutrient intake (so
      called "supplemental" parenteral nutrition). Depending on the patient's condition
      and the disease's stage, artificial nutrition may have a "permissive" role in
      patients receiving aggressive oncologic therapy or represent just a supportive
      treatment in patients likely to succumb from starvation sooner than from tumor
      progression. 

PMID- 25770334
TI  - Letter from the editor: what is the US preventive services task force?

PMID- 25770335
TI  - Letter from guest editor: radiologic screening.

PMID- 25770336
TI  - Case of the season: management of the subsolid pulmonary nodule.

PMID- 25770337
TI  - Lung cancer screening-why do it? Tobacco, the history of screening, and future
      challenges.

PMID- 25770338
TI  - Lung cancer screening: how to do it.

PMID- 25770339
TI  - Breast cancer screening: meeting the challenges of today and exploring the
      technologies of tomorrow.

PMID- 25770340
TI  - Colorectal cancer screening.

PMID- 25770341
TI  - Screening for coronary heart disease in asymptomatic patients using multidetector
      computed tomography: calcium scoring and coronary computed tomography
      angiography.

PMID- 25770342
TI  - Abdominal aortic aneurysm screening.

PMID- 25770343
TI  - Screening for carotid artery stenosis.

PMID- 25770344
TI  - Screening for peripheral artery disease.

PMID- 25770345
TI  - Use of ionizing radiation in screening examinations for coronary artery calcium
      and cancers of the lung, colon, and breast.

PMID- 25770347
TI  - The role of positive youth development practices in building resilience and
      enhancing wellbeing for at-risk youth.
AB  - Services that utilise positive youth development practices (PYD) are thought to
      improve the quality of the service experience leading to better outcomes for at
      risk youth. This article reports on a study of 605 adolescents (aged 12-17 years)
      who were concurrent clients of two or more service systems (child welfare,
      juvenile justice, additional education, mental health). It was hypothesised that
      services adopting PYD approaches would be related to increases in youth
      resilience and better wellbeing outcomes. It was also hypothesised that risks,
      resilience, service experiences and wellbeing outcomes would differ by age,
      gender and ethnicity. Youth completed a self-report questionnaire administered
      individually. Path analysis was used to determine the relationship between risk,
      service use, resilience and a wellbeing outcome measure. MANOVA was then used to
      determine patterns of risk, service use, resilience and wellbeing among
      participants based on their demographic characteristics. Services using PYD
      approaches were significantly related to higher levels of youth resilience.
      Similarly, increased resilience was related to increased indicators of wellbeing,
      suggesting the mediating role of resilience between risk factors and wellbeing
      outcomes. When professionals adopt PYD practices and work with the positive
      resources around youth (their own resilience processes) interventions can make a
      significant contribution to wellbeing outcomes for at-risk youth. 

PMID- 25770348
TI  - The anterior mini-open approach for femeroacetabular impingement: Gait and
      functional assessment at one year post-surgery.
AB  - OBJECTIVE: This study aimed to evaluate the outcome of the anterior mini-open
      approach of the hip for femoroacetabular impingement (FAI) at one year post
      surgery by use of questionnaires, functional capacity tests and biomechanical
      studies. DESIGN: This is a case series prospective study. A total of 14 patients
      diagnosed of FAI were included. Patients were classified according to Tonnis
      scale. Hip joint mobility, Faber distance, pain levels (assessed on a visual
      analogic scale [VAS]), 6-minute walking test (6MWT), Timed up & go test (TUGT),
      Stairs climbing test, Lequesne functional index, and gait analysis were assessed
      prior to and 12 months after surgery. RESULTS: Pain significantly improved
      following surgery. An improvement of 80% or more was found in 6 patients (42.85%
      of cases). Improvements were also seen in time support of the affected limb and
      in the braking force of the contralateral limb, although these are not clinically
      significant. No statistically significant changes were seen in functional
      capacity tests. At 12 months after surgery, meralgia paraesthetica presented in 3
      patients (21.4%), and a total hip arthroplasty was performed in 1 patient.
      CONCLUSIONS: There was significant reduction in pain intensity 12 months
      following mini-open approach for FAI compared to preoperatively. Improvement in
      gait analysis and functional capacity was also seen, although not statistically
      significant.

PMID- 25770346
TI  - Associations between body mass index, post-traumatic stress disorder, and child
      maltreatment in young women.
AB  - The objective of this study was to examine interrelationships between child
      maltreatment, post-traumatic stress disorder (PTSD) and body mass index (BMI) in
      young women. We used multinomial logistic regression models to explore the
      possibility that PTSD statistically mediates or moderates the association between
      BMI category and self-reported childhood sexual abuse (CSA), physical abuse
      (CPA), or neglect among 3,699 young women participating in a population-based
      twin study. Obese women had the highest prevalence of CSA, CPA, neglect, and PTSD
      (p<.001 for all). Although all three forms of child maltreatment were
      significantly, positively associated with overweight and obesity in unadjusted
      models, only CSA was significantly associated with obesity after adjusting for
      other forms of maltreatment and covariates (OR=2.21, 95% CI: 1.63, 3.00). CSA and
      neglect, but not CPA, were associated with underweight in unadjusted models;
      however, after adjusting for other forms of maltreatment and covariates, the
      associations were no longer statistically significant (OR=1.43, 95% CI: 0.90-2.28
      and OR=2.16, 95% CI: 0.90-5.16 for CSA and neglect, respectively). Further
      adjustment for PTSD generally resulted in modest attenuation of effects across
      associations of child maltreatment forms with BMI categories, suggesting that
      PTSD may, at most, be only a weak partial mediator of these associations. Future
      longitudinal studies are needed to elucidate the mechanisms linking CSA and
      obesity and to further evaluate the role of PTSD in associations between child
      maltreatment and obesity. 

PMID- 25770349
TI  - Suicide and external mortality pattern in a cohort of migrants from the former
      Soviet Union to Germany.
AB  - BACKGROUND: Mental health consequences of migration are manifold. Where some
      migrants experience migration as liberation from life threatening conditions,
      others suffer from hostility and social descent in the target country. This study
      investigates deaths due to external causes, suicides, and events of undetermined
      intent in German repatriates from the Former Soviet Union. The relation between
      age at migration and suicide mortality is also explored. METHODS: A cohort of
      German repatriates who migrated between 1990 and 1999 was followed-up until 2010.
      Each individual accumulated time at risk, expressed in person years (PY).
      Standardized mortality ratios (SMR) were calculated, supplemented by subgroup
      analyses for age and calendar year strata, and immigration period. Multivariate
      Poisson models were used to investigate the influence of age, sex, calendar year,
      number of moves, and final move distance. RESULTS: A total of 6378 German
      repatriates (3031 men, 3347 women) accumulated 92,149 PY. Median age at
      immigration was 30 years in women and 27 years in men. Women's all-cause
      mortality was significantly lower (SMR = 0.85 [0.75; 0.97]). Men more often died
      from external causes (SMR = 1.58 [1.09; 2.23]), intentional self-harm (SMR = 1.68
      [0.90; 2.88]), and events of undetermined intent such as poisoning by drugs (SMR
      = 8.07 [4.02; 14.44]). External cause mortality was significantly increased after
      1995 (SMR = 1.87). In particular, men who migrated when they were 11-20 years old
      were at strongly increased risk of committing suicide (SMR = 3.84) or dying due
      to events of undetermined intent (SMR = 14.75). CONCLUSION: The most endangered
      subgroup is men who migrated at teenage age. Protective factors such as strong
      family bounds formerly present in the FSU failed in Germany, the higher
      population density caused intense friction. The changes in the families' ethnical
      composition from mostly ethnic German members in the early 90s' towards
      predominantly Russian members around the turn of the millennium complicated
      integration. Setting-oriented prevention measures should consider the families'
      migration history, their link to culture and religion, and the different concepts
      of mental health.

PMID- 25770351
TI  - Perceptions about labor companionship at public teaching hospitals in three Arab
      countries.
AB  - OBJECTIVE: To explore the perspectives of women, female relatives, and healthcare
      providers on labor companionship. METHODS: In a qualitative study, data were
      collected from women giving birth, female family members, and healthcare staff
      via semi-structured interviews in three large public teaching hospitals in Beirut
      (Lebanon), Damascus (Syria), and Mansoura (Egypt) between May and December 2012.
      Focus groups were conducted with midwives, nurses, and medical residents. Data
      were assessed by thematic analysis. RESULTS: A total of 69 women, 57 female
      relatives, and 28 obstetricians were interviewed, and two focus groups
      discussions occurred. Women reported that being alone during labor raises
      feelings of fear and anxiety. They reported appreciating professional support,
      but found comfort in the psychological support offered by family members during
      labor. Midwives and nurses pointed to structural factors related to the
      organization of care and to the marginalization of their role as barriers to
      implementing best practices. Obstetricians referred to the absence of prenatal
      education classes, and social norms as factors impeding the organization of labor
      support initiatives. CONCLUSION: Implementing labor companionship can improve
      women's childbirth experiences and outcomes. Organizational structural barriers
      and non-supportive providers' attitudes need to be addressed to influence
      hospital practices.

PMID- 25770352
TI  - A cross-sectional study of indications for cesarean deliveries in Medecins Sans
      Frontieres facilities across 17 countries.
AB  - OBJECTIVE: To review the major indications for cesareans performed by Medecins
      Sans Frontieres (MSF) personnel from the Operational Center Brussels. METHODS: A
      retrospective study was undertaken of all singleton cesarean deliveries from 2008
      2012 for which indications were recorded. Location of project, age of patient,
      type of anesthesia, and duration of operation were also recorded. RESULTS: A
      total of 14 151 singleton cesarean deliveries were identified from 17 countries.
      Among the 15 905 indications recorded, the most common was failure to progress or
      cephalopelvic disproportion (4822 [30.3%]), followed by previous uterine scar
      (2504 [15.7%]), non-reassuring fetal status (2306 [14.5%]), and fetal
      malpresentation (1746 [11.0%]). Other indications were placenta or vasa previa
      (794 [5.0%]), uterine rupture (676 [4.3%]), hypertensive disorders (659 [4.1%]),
      placental abruption (520 [3.3%]), pre-rupture (450 [2.8%]), and cord prolapse
      (365 [2.3%]). CONCLUSION: Indications for cesareans in MSF settings differ from
      those in higher-income countries. Further investigation is needed for adequate
      emergency obstetric care coverage.

PMID- 25770353
TI  - English obesity policies: To govern and not to govern.
AB  - Problem definitions constitute a crucial part of the policy process. In 2008 the
      Labour Government presented a plan to reduce the obesity prevalence in England.
      Only three years later the Conservative-Liberal Government introduced a plan on
      the same topic, which it presented as new and innovative. The aim of this study
      is to analyse the respective governments' problematisations of obesity and to
      identify similarities and differences. Despite the different hues of the two
      governments, the programmes are surprisingly similar. They seek to simultaneously
      govern and not to govern. They adhere to liberal ideals of individual choice and
      they also suggest initiatives that will lead people to choose certain behaviours.
      Both governments encourage the food and drink industry to support their policies
      voluntarily, rather than obliging them to do so, although Labour is somewhat more
      inclined to use statutory measures. The Conservative-Liberal plan does not
      represent many new ideas. The plans are characterised by the paradox that they
      convey both ideas and ideals about freedom of choice as well as about state
      interventions to influence people's choices, which could be seen as incompatible,
      but as the study shows in practice they are not. 

PMID- 25770350
TI  - RGC-32 is a novel regulator of the T-lymphocyte cell cycle.
AB  - We have previously shown that RGC-32 is involved in cell cycle regulation in
      vitro. To define the in vivo role of RGC-32, we generated RGC-32 knockout mice.
      These mice developed normally and did not spontaneously develop overt tumors. To
      assess the effect of RGC-32 deficiency on cell cycle activation in T cells, we
      determined the proliferative rates of CD4(+) and CD8(+) T cells from the spleens
      of RGC-32(-/-) mice, as compared to wild-type (WT, RGC-32(+/+)) control mice.
      After stimulation with anti-CD3/anti-CD28, CD4(+) T cells from RGC-32(-/-) mice
      displayed a significant increase in [(3)H]-thymidine incorporation when compared
      to WT mice. In addition, both CD4(+) and CD8(+) T cells from RGC-32(-/-) mice
      displayed a significant increase in the proportion of proliferating Ki67(+)
      cells, indicating that in T cells, RGC-32 has an inhibitory effect on cell cycle
      activation induced by T-cell receptor/CD28 engagement. Furthermore, Akt and FOXO1
      phosphorylation induced in stimulated CD4(+) T-cells from RGC-32(-/-) mice were
      significantly higher, indicating that RGC-32 inhibits cell cycle activation by
      suppressing FOXO1 activation. We also found that IL-2 mRNA and protein expression
      were significantly increased in RGC-32(-/-) CD4(+) T cells when compared to RGC
      32(+/+) CD4(+) T cells. In addition, the effect of RGC-32 on the cell cycle and
      IL-2 expression was inhibited by pretreatment of the samples with LY294002,
      indicating a role for phosphatidylinositol 3-kinase (PI3K). Thus, RGC-32 is
      involved in controlling the cell cycle of T cells in vivo, and this effect is
      mediated by IL-2 in a PI3K-dependent fashion. 

PMID- 25770354
TI  - Prevalence and correlates of being overweight or obese in college.
AB  - Recent statistics indicate that over one-third of college students are currently
      overweight or obese, however, the impact of weight in this population from
      academic and psychiatric perspectives is not fully understood. This study sought
      to examine the prevalence of overweight and obesity in college students and its
      association with stress, mental health disorders and academic achievement. A
      total of 1765 students completed the College Student Computer User Survey (CSCUS)
      online at a large Midwestern United States University. Responders were classified
      by weight as normal, overweight or obese based on body mass index. Data were
      stratified by sex, with cross-tabulation and t-tests, one-way analysis of
      variance, and logistic regression for analysis. A total of 492 (27.9%) students
      were overweight (20.2%; range 25.01-29.98) or obese (7.7%; range 30.04-71.26).
      Overweight and obesity were associated with significantly lower overall academic
      achievement, more depressive symptoms, and using diet pills for weight loss.
      Obese males had significantly higher rates of lifetime trichotillomania while
      overweight and obese females reported higher rates of panic disorder. Higher
      educational institutions should be aware of the significant burden associated
      with overweight and obesity in students, and of the differing demographic and
      clinical associations between overweight or obesity in men and women. 

PMID- 25770355
TI  - Quantifying behaviors of children with Sanfilippo syndrome: the Sanfilippo
      Behavior Rating Scale.
AB  - The Sanfilippo Behavior Rating Scale (SBRS), a 68 item questionnaire, has been
      developed to assess the behavioral phenotype of children with Sanfilippo syndrome
      and its progression over time. Fifteen scales rate orality, movement/activity,
      attention/self-control, emotional function including anger and fear, and social
      interaction. Items within scales intercorrelate; measures of internal consistency
      are adequate. Twelve scales are grouped into 4 abnormality clusters: Movement,
      Lack of fear, Social/emotional and Executive Dysfunction. A Loess age-trajectory
      analysis showed that Lack of Fear, Social/Emotional and Executive Dysfunction
      increased steadily with age; Orality and Mood/Anger/Aggression leveled off.
      Movement peaked around 6years, then declined as children's excessive/purposeless
      actions stopped. Compared with standard scales, SBRS Movement was appropriately
      associated with the Vineland Motor scale; SBRS Lack of Fear had significant
      associations with the Autism Diagnostic Observation Schedule (ADOS), indicating a
      symptom overlap between Sanfilippo syndrome and autism. This suggests that
      reduced fearfulness may be the most salient/sensitive SBRS marker of disease
      progression. Volumetric MRI showed that increased Lack of Fear was significantly
      associated with reduced amygdala volume, consistent with our hypothesis that the
      behavior seen in Sanfilippo syndrome is a variant of Kluver-Bucy syndrome.
      Hippocampal volume loss had twice the effect on Social-Emotional Dysfunction as
      amygdala loss, consistent with a hippocampal role in attachment and social
      emotions. In conclusion, the SBRS assesses the Sanfilippo behavioral phenotype;
      it can measure behavior change that accompanies disease progression and/or
      results from treatment. 

PMID- 25770357
TI  - A semi-automated mass spectrometric immunoassay coupled to selected reaction
      monitoring (MSIA-SRM) reveals novel relationships between circulating PCSK9 and
      metabolic phenotypes in patient cohorts.
AB  - Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a key regulator of
      circulating low density lipoprotein cholesterol (LDL-C) levels. Besides its full
      length mature form, multiple variants of PCSK9 have been reported such as forms
      that are truncated, mutated and/or with posttranslational modifications (PTMs).
      Previous studies have demonstrated that most of these variants affect PCSK9's
      function and thereby LDL-C levels. Commercial ELISA kits are available for
      quantification of PCSK9, but do not allow discrimination between the various
      forms and PTMs of the protein. To address this issue and given the complexity and
      wide dynamic range of the plasma proteome, we have developed a mass spectrometric
      immunoassay coupled to selected reaction monitoring (MSIA-SRM) for the
      multiplexed quantification of several forms of circulating PCSK9 in human plasma.
      Our MSIA-SRM assay quantifies peptides spanning the various protein domains and
      the S688 phosphorylation site. The assay was applied in two distinct cohorts of
      obese patients and healthy pregnant women stratified by their circulating LDL-C
      levels. Seven PCSK9 peptides were monitored in plasma samples: one in the
      prodomain prior to the autocleavage site at Q152, one in the catalytic domain
      prior to the furin cleavage site at R218, two in the catalytic domain following
      R218, one in the cysteine and histidine rich domain (CHRD) and the C-terminal
      peptide phosphorylated at S688 and unmodified. The latter was not detectable in
      sufficient amounts to be quantified in human plasma. All peptides were measured
      with high reproducibility and with LLOQ and LOD below the clinical range. The
      abundance of 5 of the 6 detectable PCSK9 peptides was higher in obese patients
      stratified with high circulating LDL-C levels as compared to those with low LDL-C
      (p < 0.05). The same 5 peptides showed good and statistically significant
      correlations with LDL-C levels (0.55 < r < 0.65; 0.0002 ? p ? 0.002), but not the
      S688 phosphorylated peptide. However, this phosphopeptide was significantly
      correlated with insulin resistance (r = 0.48; p = 0.04). In the pregnant women
      cohort, none of the peptides were associated to LDL-C levels. However, the 6
      detectable PCSK9 peptides, but not PCSK9 measured by ELISA, were significantly
      correlated with serum triglyceride levels in this cohort. Our results also
      suggest that PCSK9 circulates with S688 phosphorylated at high stoichiometry. In
      summary, we have developed and applied a robust and sensitive MSIA-SRM assay for
      the absolute quantification of all PCSK9 domains and a PTM in human plasma. This
      assay revealed novel relationships between PCSK9 and metabolic phenotypes, as
      compared to classical ELISA assays.

PMID- 25770356
TI  - Engineering mesenchymal stem cells for regenerative medicine and drug delivery.
AB  - Researchers have applied mesenchymal stem cells (MSC) to a variety of therapeutic
      scenarios by harnessing their multipotent, regenerative, and immunosuppressive
      properties with tropisms toward inflamed, hypoxic, and cancerous sites. Although
      MSC-based therapies have been shown to be safe and effective to a certain degree,
      the efficacy remains low in most cases when MSC are applied alone. To enhance
      their therapeutic efficacy, researchers have equipped MSC with targeted delivery
      functions using genetic engineering, therapeutic agent incorporation, and cell
      surface modification. MSC can be genetically modified virally or non-virally to
      overexpress therapeutic proteins that complement their innate properties. MSC can
      also be primed with non-peptidic drugs or magnetic nanoparticles for enhanced
      efficacy and externally regulated targeting, respectively. Furthermore, MSC can
      be functionalized with targeting moieties to augment their homing toward
      therapeutic sites using enzymatic modification, chemical conjugation, or non
      covalent interactions. These engineering techniques are still works in progress,
      requiring optimization to improve the therapeutic efficacy and targeting
      effectiveness while minimizing any loss of MSC function. In this review, we will
      highlight the advanced techniques of engineering MSC, describe their promise and
      the challenges of translation into clinical settings, and suggest future
      perspectives on realizing their full potential for MSC-based therapy. 

PMID- 25770358
TI  - LAMP in the context of travellers' malaria: a shining light?

PMID- 25770359
TI  - [Home-based exercise training and physical activity level over one year in COPD
      patients].
AB  - INTRODUCTION: The aim of our study was to investigate whether exclusive home
      based training was feasible and effective in COPD patients and if patients have a
      persistent improvement in their level of physical activity after this
      intervention. METHODS: One hundred COPD patients (FEV1=42.6% predicted) first
      underwent 25 weekly sessions of supervised cycle ergometry training, followed by
      one year of monthly supervised follow-up. Six minutes walking test, endurance
      test, BODE index and activity monitoring were performed before, after and one
      year after inclusion. RESULTS: About 80% of the patients completed the program.
      They improved their exercise tolerance and their daily physical activity level,
      even one year after inclusion. However, more severe patients did not maintain
      these benefits. Daily physical activity quantity was also decreased in these
      patients one year after inclusion. CONCLUSION: This home-based exercise training
      program is feasible and effective. Improvements are sustainable for the majority
      of patients. However, severe patients were not able to maintain these benefits.
      Other exercise training strategies may have to be considered in these patients.

PMID- 25770361
TI  - Editorial comment.

PMID- 25770360
TI  - [Comparative diagnosis of bacterial pneumonia and pulmonary tuberculosis in HIV
      positive patients].
AB  - INTRODUCTION: Immunodepression induced by the human immunodeficiency virus (HIV)
      modifies the clinical, radiological and microbiological manifestations of
      pulmonary tuberculosis; leading to similarities between pulmonary tuberculosis
      and acute community-acquired bacterial pneumonia. A consequence is the high
      proportion of discordant pre- and post-mortem diagnoses of pneumonia. The aim of
      our study was to contribute to the improvement in the diagnosis of acute
      bacterial pneumonia in HIV positive patients in areas where tuberculosis is
      endemic. METHODS: This retrospective study in HIV positive patients has compared
      94 cases of positive smear cases pulmonary tuberculosis and 78 cases of acute
      community-acquired bacterial pneumonia. RESULTS: Using logistic regression, the
      following features were positively associated with bacterial pneumonia: the
      sudden onset of signs (OR=8.48 [CI 95% 2.50-28.74]), a delay in the evolution of
      symptoms of less than 15 days (OR=3.70 [CI 95% 1.11-12.35]), chest pain (OR=2.81
      [CI 95% 1.10-7.18]), radiological alveolar shadowing (OR=12.98 [CI 95% 4.66
      36.12) and high leukocytosis (OR=3.52 [CI 95% 1.19-10.44]). These five variables
      allowed us to establish a diagnostic score for bacterial pneumonia ranging from 0
      to 5. The area under the ROC curve was 0.886 [CI 95% 0.84-0.94, P<0.001]). Its
      specificity was >96.8% for a score of greater than or equal to 4. CONCLUSION: The
      diagnostic score for acute community-acquired pneumonia may improve the
      management of bacterial pneumonia in areas where tuberculosis is endemic.

PMID- 25770363
TI  - Pediatric surgical transitional care. Preface.

PMID- 25770364
TI  - Federal policy supporting improvements in transitioning from pediatric to adult
      surgery services.
AB  - For children with complex medical conditions that require ongoing surgical
      intervention, planning for the transition from pediatric to adult surgical care
      is essential. Services that support healthcare transition from specialty
      pediatric practices into adult practices are often inadequate, and the healthcare
      policy process has been slow to respond to the call to action by both
      professional and patient organizations. However, The Patient Protection and
      Affordable Care Act of 2010 (PPACA), arguably the most significant healthcare
      reform legislation since the enactment of Medicaid and Medicare in the mid-1960s,
      includes several provisions with direct influence on access to care and quality
      for adolescents transitioning to adult surgical care. We present a brief
      background on the rationale for improving surgical transition plans, the
      challenges of enacting the plans, and the relevance of PPACA in shaping health
      policy change around transition to adult services. 

PMID- 25770365
TI  - Transition of care in pediatric surgical patients with complex gastrointestinal
      disease.
AB  - Pediatric surgeons provide care for infants and children with a wide variety of
      conditions throughout the body. Many of these conditions are congenital or occur
      very early in life, and for this reason, providing continuity of care for these
      patients into adulthood is an emerging challenge. In the gastrointestinal tract,
      congenital and acquired conditions are now associated with excellent long-term
      prognosis; however, little guidance on long-term care exists. The aim of this
      article is to discuss aspects that are important to transitioning care of
      pediatric surgical patients with complex gastrointestinal disorders from
      pediatric to adult practitioners. Transitional care of patients with short bowel
      syndrome, Hirschsprung Disease, and anorectal malformations will be the focus of
      this discussion, but the concepts introduced here may translate to other
      diagnoses as well. 

PMID- 25770366
TI  - Transition of care in congenital heart disease from pediatrics to adulthood.
AB  - Improvement in surgical techniques, anesthesia, and perioperative care has
      resulted in the majority of children born with congenital heart defects surviving
      into adulthood with a normal or near-normal quality of life. A careful transition
      from pediatric to adult care providers is important to avoid issues related to
      loss of continuity of care and any undue financial or psychological burdens to
      the patients and their families. The patients, their families, and the health
      care providers are faced with many challenges during this transition process that
      can be optimized and overcome by education about the heart defects and a team
      approach with clear lines of communication. This review addresses the challenges
      related to the transition of care from pediatrics to adults and provides the
      necessary recommendations to ensure a smooth transition process. 

PMID- 25770367
TI  - Transitional care in pediatric urology.
AB  - The transition from childhood to adolescence and into adulthood occurs as a
      natural component of human development. As children progress through school and
      gain independence, health care practitioners must facilitate a parallel
      transition from pediatric to adult providers. Modern medicine has succeeded in
      extending the life expectancy for many children with complex conditions, and
      adult providers are participating in their medical care through adulthood.
      Transitioning pediatric urology care to adult urology care is unique to every
      individual and his or her underlying condition, while the transition process is
      universal. The objectives of all pediatric urologists include preservation of the
      kidneys and lower urinary tracts, safe urine storage, safe urine drainage,
      urinary continence, fertility, sexual function, and genital cosmesis. For some
      children, these objectives can be attained during childhood, while other children
      require lifelong maintenance and management. Children with posterior urethral
      valves, exstrophy-epispadias complex, cloaca, vesicoureteral reflux, neurogenic
      bladder, disorders of sex development, cancer, hypospadias, nephrolithiasis,
      undescended testes, varicoceles, ureteropelvic junction obstruction, solitary
      kidney, and upper tract anomalies all require long-term evaluation and
      management. The obstacles of altering a patient and caregiver paradigm, locating
      adult urologists with special expertise, coordinating care with other adult
      specialties such as nephrology, and navigating the adult health care environment
      can impede the transition process. 

PMID- 25770368
TI  - Transitional care in pediatric neurosurgical patients.
AB  - The relatively young specialty field of pediatric neurosurgery addresses a number
      of surgical diseases that, while first encountered in children, may involve long
      term post-operative sequelae that persist into adulthood. These diagnoses present
      a challenge for care providers as patients transition from pediatric to adult age
      groups. Brain tumors, shunted hydrocephalus, and myelomeningocele are three of
      the most common examples of this interesting category. The provision of
      coordinated transitional care to affected pediatric neurosurgical patients is
      made all the more difficult by the common comorbidity of developmental delay,
      affecting not only personal and social growth but also the character and
      composition of the care team. This article seeks to provide a background for some
      of the common pediatric neurosurgical diseases requiring a transitional care
      framework for survivors entering young adulthood, a summary of the adult surgical
      care challenges faced by these patients, and a rationale for different approaches
      to optimize care. 

PMID- 25770369
TI  - Transitional care in solid organ transplantation.
AB  - Pediatric solid organ transplantation has become an accepted modality of
      treatment in the last few decades. The number of childhood recipients of solid
      organ transplantation surviving to adulthood is correspondingly rising. This
      review examines the epidemiology of pediatric solid organ transplant recipients,
      and the challenges faced during transition to adult services, with suggestions
      for improvement in collaborative and coordinated care. Transition to adulthood
      has been established as a vulnerable period for recipients of a solid organ
      transplant. Assessment of readiness for transfer, allowing sufficient time for
      preparation before the actual transfer, involvement of all stakeholders, and
      inclusion of a transition coordinator are some of the components that can
      facilitate successful transition to the adult transplant program. This
      programmatic approach improves both quality of life and long-term graft and
      patient survival. Moreover, the economic benefits associated with avoiding
      frequent hospitalizations for graft dysfunction and preventing re-transplantation
      more than compensate for the costs related to establishing and maintaining a
      robust transition program. 

PMID- 25770370
TI  - Transition from pediatric to adult surgery care for patients with disorders of
      sexual development.
AB  - Disorders of sexual development (DSDs) are relatively rare congenital conditions
      in which the development of the chromosomal, gonadal, or anatomic sex is
      atypical. Some conditions may not manifest until puberty or adulthood. The
      examination and workup of either an infant or an older patient with suspected DSD
      should be directed and performed systematically by a multidisciplinary team.
      Ideally, the team will include those with not only an interest in DSD but also
      experience with this group of patients. This article will briefly orient the
      reader to the conditions and decisions that may have been made during infancy,
      childhood, and adolescence and then focus on the challenges that may accompany
      transitioning the care of DSD patients from pediatric to adult surgeons and
      specialists to enable appropriate decisions and care. The actual transition will
      optimally involve a well-developed action plan that will take place gradually
      over a number of years as the person becomes educated about their condition and
      empowered to participate knowingly and actively in their own care. 

PMID- 25770371
TI  - Childhood cancer survivors: considerations for surgeons in the transition from
      pediatric to adult care.
AB  - There are over 380,000 childhood cancer survivors (CCS) alive in the US, and the
      population is growing. CCS face significant long-term morbidity and mortality as
      a consequence of their cancer treatment and thus require lifelong, risk-based
      health care focused on surveillance and early intervention to minimize the impact
      of late effects and second malignant neoplasms (SMN). Surgeons play a critical
      role in the treatment of childhood cancer and the subsequent management of long
      term health complications. In this review, we provide an overview of late effects
      associated with cancer surgeries, potential late effects that may require surgery
      as an adult, and cancer therapies that may impact future safe surgery and
      anesthesia. We also describe the barriers to successful transition from pediatric
      to adult health care for CCS and the importance of treatment summaries,
      surveillance guidelines, and survivorship care plans for surgeons caring for CCS.

PMID- 25770372
TI  - Antimicrobial drug-resistant microbes have a higher risk of health care
      associated pneumonia in eastern Taiwan.

PMID- 25770373
TI  - Evaluation of a noise reduction imaging technology in iliac digital subtraction
      angiography: noninferior clinical image quality with lower patient and scatter
      dose.
AB  - PURPOSE: To determine whether equivalent-quality images can be obtained from
      digital subtraction angiography (DSA) of the iliac artery after implementation of
      a novel imaging technology that reduces patient and scatter x-ray dose. MATERIALS
      AND METHODS: Imaging using two randomly ordered DSA runs was performed in 51
      adults scheduled for iliac artery angiography or intervention or both. One DSA
      run used standard acquisition chain and image processing algorithms (referred to
      as " reference DSA"), and the other DSA run used dose-reduction and real-time
      advanced image noise reduction technology (referred to as "study DSA"). The
      quality of each pair of runs, consecutively performed without changes in working
      projection or injection parameters, was independently rated by five radiologists
      blinded to the imaging technology used. Patient radiation dose was evaluated
      using air kerma and dose area product, and scatter dose was evaluated using three
      dosimeters (DoseAware, Philips Healthcare, Best, The Netherlands), located at
      fixed positions. RESULTS: Comparable image pairs were available in 48 patients.
      There were 44 patients undergoing treatment involving the common (n = 33) or
      external (n = 29) iliac arteries. Study DSA images were rated as equal to or
      better than reference DSA images for 96% of comparisons, with an average overall
      agreement among raters of 0.93 (95% confidence interval, 0.65-0.96). Mean patient
      radiation dose (n = 48) and scatter dose rate for the three dosimeters (n = 50)
      was 83% +/- 5 and 69% +/- 10 lower, respectively, using the study technology (P <
      .001). CONCLUSIONS: Iliac artery DSA performed using a dose-reduction and real
      time advanced image noise reduction technology results in image quality that is
      noninferior to conventional DSA but with significantly lower patient and scatter
      radiation exposure (P < .001).

PMID- 25770374
TI  - Sulcus Vocalis (Type III): Prevalence and Strobovideolaryngoscopy
      Characteristics.
AB  - OBJECTIVES: The reported prevalence of sulcus vocalis (SV)/type III, a pathologic
      groove in the vibratory margin of the vocal fold, varies greatly in the
      literature. Difficulties in visualizing the defect and a variety of descriptions
      have complicated the evaluation of SV. The objective of this study was to
      determine the prevalence of SV by reviewing strobovideolaryngoscopy (SVL)
      examinations in subjects with and without dysphonia. STUDY DESIGN: Retrospective
      chart review. METHODS: Charts and SVL images were reviewed for subjects with and
      without dysphonia and analyzed using standard statistical techniques. RESULTS:
      SVL images were reviewed for 94 nondysphonia subjects and 100 dysphonia subjects.
      For all subjects, 19.6% had type I, 2.1% had type II, and 5.7% had type III/SV.
      Per vocal fold, 14.7% had type I, 1.3% had type II, 3.1% had type III/SV and
      13.1% had scar. The prevalence of SV per subject was not significantly different
      between the two groups (8% of dysphonia subjects, 3.2% of nondysphonia subjects).
      Male gender, decreased amplitude, decreased waveform, and hypodyamic motion were
      significantly higher in the dysphonia SV subjects compared with the non-SV
      subjects. All other SVL characteristics were not significantly different in
      subjects with SV compared with non-SV subjects. CONCLUSIONS: We report a
      prevalence of SV/type III at 3.1% (per vocal fold) and 5.7% (per subject). Higher
      frequencies of male gender and waveform abnormalities were seen in the dysphonia
      SV subjects only. There were no significant differences in nondysphonia subjects
      with or without SV.

PMID- 25770375
TI  - The effects of articulation on the perceived loudness of the projected voice.
AB  - Arthur Lessac developed a voice training approach that concentrated on three
      energies: structural action, tonal action, and consonant action. In Lessac-Madsen
      Resonant Voice Therapy (LMRVT), speech-language pathologists help patients
      achieve a resonant voice through structural posturing and awareness of tonal
      changes. However, LMRVT many not necessarily include the third component of
      Lessac's approach: consonant action.This study examines the effect that increased
      effort on consonant production has on the speaking voice-particularly regarding
      vocal loudness and projection. METHODS: Audio samples were collected from eight
      actor participants who read a monologue using three distinct styles: normal
      articulation, poor articulation (elicited using a bite block), and
      overarticulation (elicited using a Lessac-based training intervention). Twenty
      graduate students of speech-language pathology listened to speech samples from
      the different conditions and made comparative judgments regarding articulation,
      loudness, and projection. RESULTS: Group results showed a strong correlation
      between the articulatory condition and the level of perceived loudness and
      projection. That is, as precision of articulation increased, the ratings of
      perceived loudness and projection increased, as well. CONCLUSIONS: These findings
      indicate that articulation treatment may have a positive influence on the
      perception of vocal loudness and projection. This has implications for future
      directions in expanding voice therapy modalities.

PMID- 25770376
TI  - The Effect of Traditional Singing Warm-Up Versus Semioccluded Vocal Tract
      Exercises on the Acoustic Parameters of Singing Voice.
AB  - OBJECTIVES/HYPOTHESES: This study investigated the effect of traditional vocal
      warm-up versus semioccluded vocal tract exercises on the acoustic parameters of
      voice through three questions: does vocal warm-up condition significantly alter
      the singing power ratio of the singing voice? Is singing power ratio dependent
      upon vowel? Is perceived phonatory effort affected by warm-up condition?
      Hypotheses were that vocal warm-up would alter the singing power ratio, and that
      semioccluded vocal tract warm-up would affect the singing power ratio more than
      no warm-up or traditional warm-up, that singing power ratio would vary across
      vowel, and that perceived phonatory effort would vary with warm-up condition.
      STUDY DESIGN: This study was a within-participant repeated measures design with
      counterbalanced conditions. METHODS: Thirteen male singers were recorded under
      three different conditions: no warm-up, traditional warm-up, and semioccluded
      vocal tract exercise warm-up. Recordings were made of these singers performing
      the Star Spangled Banner, and singing power ratio (SPR) was calculated from four
      vowels. Singers rated their perceived phonatory effort (PPE) singing the Star
      Spangled Banner after each warm-up condition. RESULTS: Warm-up condition did not
      significantly affect SPR. SPR was significantly different for /i/ and /e/. PPE
      was not significantly different between warm-up conditions. CONCLUSIONS: The
      present study did not find significant differences in SPR between warm-up
      conditions. SPR differences for /i/, support previous findings. PPE did not
      differ significantly across warm-up condition despite the expectation that
      traditional or semioccluded warm-up would cause a decrease.

PMID- 25770377
TI  - Vocal Fold Adjustment Caused by Phonation Into a Tube: A Double-Case Study Using
      Computed Tomography.
AB  - OBJECTIVES: Phonation into a tube is a widely used method for vocal training and
      therapy. Previous studies and practical experience show that the phonation
      becomes easier and louder after such an exercise. The purpose of this study was
      to find out whether there are systematic changes in the vocal fold adjustment
      after the exercise. METHODS: Two volunteer subjects (1 male and 1 female) without
      voice disorders were examined with computed tomography (CT). Both produced a
      sustained vowel [a:] at comfortable pitch and loudness before and after the tube
      phonation and a vowel-like phonation into the tube. Computed tomography (CT)
      scans were obtained before, during, and after the exercise, twice for each
      condition. The gathered CT images were used for measurements of vertical vocal
      fold thickness, bulkiness, length, and glottal width. RESULTS: No prominent
      trends common to both subjects were found in vocal fold adjustment during and
      after the phonation into the tube. Variability observed under the same conditions
      was usually of the same magnitude as the changes before and after the tube
      phonation. CONCLUSIONS: Changes in vocal tract configuration observed after the
      resonance tube exercises in previous related studies were more prominent than the
      changes in vocal fold configuration observed here.

PMID- 25770378
TI  - Update on the role of the distal arteriovenous fistula as an adjunct for
      improving graft patency and limb salvage rates after crural revascularization.
AB  - BACKGROUND: Critical ischemia of the lower limb continues to challenge the
      ingenuity of all interventionalists in achieving reliable, predictable, and
      durable patency. The objective of this study was to investigate the role of the
      distal arteriovenous fistula (dAVF) to enhance crural revascularization patency
      rates particularly when prosthetics are used. METHODS: All patients who underwent
      crural bypass with dAVF since 1979 were included. Graft patency was assessed
      periodically by clinical examination and Doppler studies. Results were analyzed
      by life-table methodology to obtain primary and secondary patency rates and limb
      salvage rates. RESULTS: A total of 502 crural bypass plus dAVF procedures were
      studied within 4 consecutive periods. Primary patency rates at 1 and 3 years for
      each of the 4 consecutive periods were (1) 36% and 10%, (2) 52% and 15%, (3) 54%
      and 31%, and (4) 70% and 46%. Corresponding secondary patency rates were (1) 43%
      and 17%, (2) 60% and 29%, (3) 60% and 44%, and (4) 72% and 50%. There was a
      statistically significant improvement for primary and secondary patency rates
      when comparing the last 2 periods with the first 2. Limb salvage rates also
      showed significant improvement for the same periods. CONCLUSIONS: Creation of a
      dAVF should be considered as a component of crural revascularization when
      prosthetics are used. The altered hemodynamics associated with dAVF prevents
      overload and as a consequence, potential bypass closure. The contribution of dAVF
      for enhancing patency rates when autologous vein is used with compromised runoff
      requires further study.

PMID- 25770379
TI  - Intraluminal thrombus attached to the lesser curvature of the aortic arch and
      cerebral ischemic stroke after its surgical removal.
AB  - Some cases of thrombi at the ascending and descending aorta have been reported,
      but there are only a few reports of intraluminal aortic arch thrombi. Most
      intraluminal thrombi are associated with atherosclerotic lesions at the aortic
      wall. Here, we report a case of an intraluminal thrombus attached to the lesser
      curvature of the aortic arch. The thrombus was successfully and completely
      excised, and the pathologic study suggested no obvious atherosclerotic changes in
      the aortic wall. Two months after surgical removal of the thrombus, the patient
      suffered a severe cerebral ischemic stroke caused by a newly formed
      thromboembolism in the innominate artery. 

PMID- 25770380
TI  - Endovascular treatment of abdominal aortic aneurysm in a 26-year-old man. A case
      report and 10-year follow-up.
AB  - We present endovascular treatment of abdominal aortic aneurysm in a 26-year-old
      man with a 10-year follow-up. A young patient presenting with an abdominal aortic
      aneurysm is extremely rare, and data describing this population are limited. Open
      aneurysm repair (OAR) is the treatment of choice in these patients. However,
      since its introduction, endovascular aneurysm repair (EVAR) has revolutionized
      the treatment of abdominal aortic aneurysms. The long-term durability and late
      complications after EVAR may have more significance when considering the optimal
      treatment for young patients with a longer life expectancy. Our good long-term
      outcome will help to support the use of EVAR as a reasonable alternative to OAR
      in young patients with suitable anatomic findings.

PMID- 25770381
TI  - Incidental discovery of a chronically thrombosed abdominal aortic aneurysm: case
      report and literature review.
AB  - Chronic spontaneously thrombosed abdominal aortic aneurysms (AAAs) are rare. We
      present a patient with a completely thrombosed abdominal aortic aneurysm found
      incidentally on imaging for evaluation of unrelated abdominal pain. The patient
      was asymptomatic with regards to the aneurysm due to extensive collateralization
      of the intercostal and lumbar arteries to the bilateral hypogastric and internal
      mammary arteries to the common femoral arteries bilaterally. Follow-up imaging
      after 10 months showed no aneurysmal change. Further study is needed regarding
      indications for elective repair, medical therapy, and surveillance modality and
      schedule for patients with chronically occluded AAAs as these patients are at
      risk for aneurysm rupture and thrombus propagation.

PMID- 25770382
TI  - Extra-anatomic endovascular repair of an abdominal aortic aneurysm with a
      horseshoe kidney supplied by the aneurysmal aorta.
AB  - Abdominal aortic aneurysm complicated by a horseshoe kidney (HSK, fused kidney)
      represents a unique challenge for repair. Renal arteries arising from the
      aneurysmal aorta can further complicate intervention. Reports exist describing
      the repair of these complex anatomies using fenestrated endografts, hybrid open
      repairs (debranching), and open aneurysmorrhaphy with preservation of renal
      circulation. We describe an extra-anatomic, fully endovascular repair of an
      abdominal aortic aneurysm with a HSK partially supplied by a renal artery arising
      from the aneurysm. We successfully applied aortouni-iliac endografting,
      femorofemoral bypass, and retrograde renal artery perfusion via the contralateral
      femoral artery to exclude the abdominal aortic aneurysm and preserve circulation
      to the HSK.

PMID- 25770383
TI  - Endovascular treatment of a symptomatic vertebral artery pseudoaneurysm.
AB  - A 35-year-old patient was brought to the emergency department referring
      dysarthria, left ear tinnitus for 5 min, and short-lasting blindness, with
      headache in the 45 min before the clinical presentation. In the magnetic
      resonance imaging, an acute-subacute lesion in the cerebellum right-anterior lobe
      (in the territory of the cerebellum anterior artery) and a dilatation near the
      ostium of the right vertebral artery were seen. For a better assessment, an Angio
      CT was done, showing a 9-mm saccular pseudoaneurysm of the right vertebral artery
      close to the origin of the vessel, without being able to determine if it had been
      caused because of a dissection. The rest of the study (cerebral vessels and supra
      aortic vessels) showed no disorders. He was operated under local anesthesia and
      sedation a week after the onset of the symptoms. Through a 0.014 wire, a
      Biotronik PK Papyrus balloon-expandable covered cobalt-chromium stent was
      deployed covering the hole in the artery. Antiplatelet drugs were prescribed, and
      the patient was discharged 24 hr after surgery. He has remained symptom free
      since then.

PMID- 25770384
TI  - Operative interventions for extrahepatic portomesenteric venous aneurysms and
      long-term outcomes.
AB  - BACKGROUND: Extrahepatic portal venous aneurysms (PVAs) are rare, and the
      pathogenesis is not fully understood. The optimum management of these patients is
      unknown. METHODS: Consecutive patients with PVA were identified over an 18-year
      period (1992-2010). A retrospective review was conducted. Clinical presentation,
      modality of diagnosis, surgical treatment, 30-day morbidity and mortality, and
      follow-up are reported. RESULTS: Four patients were identified who underwent
      surgical management of an extrahepatic PVA. Operative technique using left renal
      vein, femoral vein panel graft, polytetrafluoroethylene (ePTFE) graft, and
      segmental aneurysm wall resected with aneurysmorrhaphy is described. Early
      complications occurred in 1 patient with an ePTFE graft. The patient returned to
      the operating room for bleeding. In addition, the same patient had a late graft
      thrombosis 6 years postoperatively when the anticoagulation was discontinued for
      pregnancy. The remainder of the patients recovered without complication, and
      their repairs are still patent with a mean follow-up of 78 months (17-144
      months). There were no mortalities in the series. CONCLUSIONS: Operative
      intervention for portomesenteric venous aneurysm can be done safely in select
      patients and should be considered in those with symptoms, rapid growth, mural
      thrombus, or aneurysms >=4 cm in diameter. Repair with an autogenous
      interposition graft affords good long-term patency. Aneurysmorrhaphy may be
      performed if the remaining venous wall is of good quality.

PMID- 25770385
TI  - Current factors of fragility and delirium in vascular surgery.
AB  - BACKGROUND: Vascular surgery patients are frequently deemed to be in a frail
      clinical condition and at risk for delirium. Therefore, we evaluated the
      incidence and independent perioperative risk factors for delirium. In addition,
      we describe factors on frailty in the various vascular disease groups in current
      practice. METHODS: This observational longitudinal study included 206 selected
      patients who were referred to a vascular surgery ward of a large-sized teaching
      hospital (Amphia Hospital, Breda, The Netherlands) for critical limb ischemia (n
      = 80), diabetic foot ulcers (n = 27), abdominal aortic aneurysm (AAA) (n = 62),
      and carotid surgery (n = 37) between April 2013 and December 2013. Data on
      factors that characterize frailty were collected. Delirium was scored using the
      Delirium Observation Screening Scale. Multivariable logistic regression analysis
      was performed to find independent risk factors for delirium. RESULTS: Delirium
      was present in 24% of the critical limb ischemia patients, in 19% of the patients
      with a diabetic foot ulcer, in 7% of the patients with an AAA, and in 8% of the
      patients undergoing carotid surgery (P > 0.05). Of the patients with critical
      limb ischemia and a delirium, 53% were octogenarians. Multivariable stepwise
      logistic regression analysis revealed that history of delirium and nurse help at
      patient's home were independently associated with delirium. Patients with
      critical limb ischemia scored worse on factors related to frailty compared with
      the other disease groups in our current clinical practice on vascular surgery.
      CONCLUSIONS: Delirium is a frequent complication in vascular surgery clinical
      practice, especially in the elderly. Nurse visits at patients' homes and the
      Amphia Risk Score for delirium were independent risk factors for delirium in our
      study population. In this study, we identified patients with critical limb
      ischemia as the most frail and vulnerable.

PMID- 25770386
TI  - Bifurcated aortoiliac endograft limb occlusion during deployment and its bailout
      conversion using the external iliac artery to internal iliac artery endograft
      technique.
AB  - Endovascular aneurysm repair has become the preferred method to treat abdominal
      aortic aneurysms (AAAs). The Ovation TriVascular Stent-Graft system introduces a
      unique concept of separation of the metal (stent) and fabric (graft) portion of
      the endograft's main body to facilitate delivery through ultra-low profile 14F
      devices. In the setting of a narrow distal aneurysmal lumen, usually due to the
      presence of thrombus, deployment of this endograft may be complicated by folding
      and collapse of the (unsupported by a stent) aortic body or limbs, making
      catheterization and ballooning impossible. We present a case of Ovation endograft
      contralateral limb collapse in a tight AAA lumen due to thrombus deposition,
      which led to folding and total occlusion of the limb and made limb
      catheterization impossible. This is a real-life example of how the external iliac
      artery to internal iliac artery endograft technique may be used as a bailout
      procedure, converting the procedure into an aortouni-iliac graft. To our
      knowledge, this is the first reported bailout use of this technique in English
      literature which may be used in selected cases.

PMID- 25770387
TI  - Cavoatrial thrombectomy without the use of cardiopulmonary bypass for abdominal
      tumors. Our experience and state of the art.
AB  - BACKGROUND: Surgical resection of a tumor with thrombus formation extending from
      the inferior vena cava (IVC) to the right atrium can be performed without the use
      of a cardiopulmonary bypass. However, this technique is not widely known or used
      by general surgeons. Our aim was to present our experience in a general surgical
      unit setting and to present a literature review. METHODS: Retrospective analysis
      of 3 cases with successful cavoatrial thrombectomy without the use of
      cardiopulmonary bypass by a transabdominal, transdiaphragmatic, and
      transpericardic approach. We also performed a review of the English literature of
      this procedure. RESULTS: Three cases are presented: right-sided hepatocellular
      carcinoma, a right renal carcinoma, and a recurrent hepatic hydatid cyst all
      which required surgery. An approach from the right atrium to the IVC was used,
      and then, after cavoatrial occlusion, a cavotomy was performed to carry out the
      thrombectomy. In all cases, a transesophageal echocardiography was performed
      during surgery. We only found 6 other similar cases that were performed
      successfully in current medical literature. CONCLUSIONS: Our own experiences and
      cases identified through a literature review demonstrate that a thrombectomy for
      IVC thrombus in the setting of abdominal pathology can be performed successfully
      in selected cases without the support of cardiopulmonary bypass.

PMID- 25770388
TI  - Long-segment plication technique for arteriovenous fistulae threatened by diffuse
      aneurysmal degeneration: short-term results.
AB  - BACKGROUND: A substantial number of patients with autologous arteriovenous
      fistulas (AVFs) develop diffuse aneurysmal degeneration, which frequently
      interferes with successful access. These AVFs are often deemed unsalvageable. We
      hypothesize that long-segment plication in these patients can be performed safely
      with acceptable short-term AVF salvage rates. METHODS: We reviewed a
      prospectively maintained database to identify all patients with extensive AVF
      aneurysmal disease operated on for this problem. RESULTS: Thirty-five patients,
      25 (71%) male and 10 (29%) female were operated on between July 2012 and January
      2014. AVFs included 23 (66%) brachiocephalic, 5 (14%) radiocephalic, and 7
      brachiobasilic (20%) fistulae (one first stage only but in use). The cohort had
      one or a combination of local pain, arm edema, cannulation issue, recurrent
      thrombosis, dysfunctional during dialysis, or extreme tortuousity. Time range for
      AVF creation to consultation ranged from 3 months to 11 years. All underwent long
      segment plication over a 20-Fr Bougie with or without segmental vein resection; 3
      underwent concomitant first rib resection for costoclavicular stenosis; 21
      patients had tunneled catheter placement for use while healing, whereas 13 were
      allowed segmental use of their AVF during the perioperative period (1 patient was
      not yet on dialysis). Early in our experience, AVFs were left under the wound,
      whereas all but one repaired since early 2013 were left under a lateral flap. All
      patients were followed by clinical examination and duplex. In the 30-day
      postoperative period, 2 AVFs (5.7%) became infected requiring excision, 2
      occluded (5.7%), 1 day 1 and the other at 24 days out, 1 patient developed steal
      and required DRIL 1 week postoperatively, and 1 patient died, unrelated to his
      surgery. Postoperative functional primary patency was 88% (30 of 34). Of the
      patients needing temporary access catheter, mean time to first fistula use was 44
      days. No wound or bleeding complications have occurred in repaired AVF left under
      skin flaps. CONCLUSIONS: In this group of patients whose access was threatened by
      diffuse aneurysmal degeneration, long-segment placation allowed salvage of 88% of
      fistulae with relatively low morbidity. Fewer complications are associated by
      covering the revised fistula with intact skin.

PMID- 25770389
TI  - Spontaneous isolated superior mesenteric artery dissection: genetic heterogeneity
      of chromosome locus 5q13-14 in 2 male familial cases.
AB  - Spontaneous isolated superior mesenteric artery dissection (SISMAD) is a rare
      disease that occurs sporadically. In this report, we describe 2 cases of SISMAD
      involving an uncle and his nephew. Genetic studies revealed the presence of
      heterogeneity of a chromosome locus at 5q13-14 in 3 family members (the 2
      patients and the nephew's mother), an area previously found to be linked to
      familial ascending aortic aneurysms and dissections. 

PMID- 25770390
TI  - Spiral saphenous vein graft for major pelvic vessel reconstruction during
      exenteration surgery.
AB  - This article describes a great saphenous vein spiral graft technique for
      reconstruction of iliac vessels after en bloc resection during pelvic
      exenteration. Use of different size syringes as a scaffold allows the surgeon to
      construct autologous vascular interposition conduits of variable diameter to
      match the luminal size of the vessel requiring reconstruction. Autologous
      vascular grafts are preferred in exenteration surgery in which the operative
      field is commonly contaminated by concomitant bowel resection, which carries an
      increased risk of graft infection. 

PMID- 25770391
TI  - Infrapopliteal bifurcated dual run-off bypass in critical limb ischemia: a report
      of 2 cases.
AB  - Recently, angiosome-oriented direct revascularization was advocated for
      infrapopliteal bypass in patients with critical limb ischemia. However, angiosome
      matched target vessels, which supply direct blood flow into the ischemic tissue,
      are frequently small in diameter, severely calcified, have a very poor vascular
      bed, and might not be suitable technically for distal anastomosis. In such cases,
      creating a bifurcation in the graft could enable perfusion of a "direct" target
      vessel with poor quality and an "indirect" run-off vessel with better features.
      In this report, we present 2 cases of bifurcated dual run-off bypass (BDRB) in
      which we added a secondary outflow to the original single tibial bypass. Careful
      investigation and evaluation of the status of the collateral vessels and
      additional information regarding successful and unsuccessful cases are required
      to further understand the advantages and disadvantages of BDRB.

PMID- 25770392
TI  - Surgical ligation of portosystemic shunt to resolve severe hematuria and
      hemafecia caused by type II abernethy malformation.
AB  - The purpose of this study was to report the use of venous pressure measurement
      during surgery for Abernethy malformation (AF). This is a case report of a 19
      year-old man who suffered from hematuria and hemafecia for 3 months with
      worsening symptoms a week before being sent to the emergency room. He was
      diagnosed with type II AF based on portal phlebography. We performed an open
      surgery; measured portal vein, inferior mesenteric vein (IMV), and inferior vena
      cava pressure; and decided to completely suture the IMV. Anticoagulation therapy
      was used during follow-up, and CTV showed increased portal vein diameter at 12
      months after the procedure. For type II AF, measuring extrahepatic portal venous
      pressure changes before and after shunt blockage during surgery can help
      determine whether it is feasible to block the shunt, and anticoagulation therapy
      can improve patient prognosis.

PMID- 25770393
TI  - Graphite moderated (252)Cf source.
AB  - The Thorium molten-salt reactor is an attractive and affordable nuclear power
      option for developing countries with insufficient infrastructure and limited
      technological capability. In the aim of personnel training and experience
      gathering at the Universidad Simon Bolivar there is in progress a project of
      developing a subcritical thorium liquid-fuel reactor. The neutron source to run
      this subcritical reactor is a (252)Cf source and the reactor will use high-purity
      graphite as moderator. Using the MCNP5 code the neutron spectra of the (252)Cf in
      the center of the graphite moderator has been estimated along the channel where
      the liquid thorium salt will be inserted; also the ambient dose equivalent due to
      the source has been determined around the moderator. 

PMID- 25770394
TI  - Improving operating room efficiency via an interprofessional approach.
AB  - BACKGROUND: Third-party payer reimbursements will likely continue to decrease.
      Therefore, it is imperative for operating rooms (ORs), often a hospital's largest
      revenue source, to improve efficiency. We report the outcome after 3 years of a
      lean, Six Sigma program to improve OR utilization. METHODS: In January 2011, our
      hospital system instituted a facility-wide approach to address the problem of OR
      efficiency. Interprofessional teams were formed to examine all aspects of OR use.
      An OR Governance Committee consisting of Department Chairs, nursing and senior
      administration oversaw the project. RESULTS: Outpatients' readiness on time for
      surgery increased from 59% to 95%, while first case on-time starts improved from
      32% to 73%. Block utilization went from 68% to 74% and actual room utilization
      improved from 56% to 68%. The number of cases increased by 9%. Overtime went from
      7% of total to 4%, so personnel costs decreased 14% despite 26% more employees.
      There was a reduction in annual voluntary OR staff turnover from 28% to 11%.
      Revenues increased more than 10% annually. CONCLUSION: A concerted effort to
      optimize OR performance resulted in marked improvements in access, overall case
      efficiency, staff satisfaction, and financial performance.

PMID- 25770395
TI  - Mesh wrapping for severe hepatic injury: a beneficial option in the trauma
      surgeon's armamentarium.
AB  - BACKGROUND: The purpose of this study was to assess the efficacy of absorbable
      mesh wrapping (MW) versus perihepatic packing (HP) for severe hepatic injury.
      METHODS: From January 2001 to December 2012, data were collected for MW patients
      with hepatic injury. Patients who underwent HP were matched with MW patients by
      injury mechanism, liver injury grade, Injury Severity Score, and age. RESULTS:
      Twenty-six MW and twenty-six HP patients were matched. Eighteen blunt and 8
      penetrating injuries were present in each group. There were 9 (35%) mortalities
      in the MW group and 16 (62%) in the HP groups (P = .03). Average transfusions
      were 12.0 and 24.5 (P = .03) packed red blood cells in the MW and HP groups,
      respectively. Average laparotomies per survivors were 1.3 for the MW and 3.1 for
      the HP groups (P = .01). Average length of stay for survivors was 19 and 47 (P =
      .04) days in the MW and HP groups, respectively. CONCLUSION: MW for hepatic
      injuries can significantly decrease mortality, transfusions, laparotomies, and
      length of stay.

PMID- 25770396
TI  - Intussusception in adults and the role of evolving computed tomography
      technology.
AB  - BACKGROUND: The purpose of this study was to describe a single institution's
      experience with adult intussusception and determine how this was influenced by
      evolving computed tomography (CT) technology. METHODS: Adults treated between
      1978 and 2013 for intussusception were reviewed. CT utilization and utilization
      of multislice technology over time were determined. Sensitivity of CT was
      calculated. RESULTS: A total of 318 patients were identified. CT utilization was
      72% and it increased over time. The number of channels ranged from 1 to 128. CT
      sensitivity was greater than 85% for single and multislice scanners. A lead point
      was identified in 69% of patients and a malignancy in 40%. Surgical exploration
      was required in 60% of patients and 40% were managed nonoperatively. CONCLUSIONS:
      The diagnosis of intussusception in adults is increasing over time, particularly
      idiopathic intussusception. This is associated with increased utilization of
      highly sensitive CT technology, which facilitates the safe nonoperative
      management in many patients.

PMID- 25770397
TI  - Oncotype DX((r)) colon cancer assay for prediction of recurrence risk in patients
      with stage II and III colon cancer: A review of the evidence.
AB  - Advances in molecular biology have enabled identification of tumor biomarkers
      that allow for individualized risk assessment for patients with cancer. Molecular
      predictors of clinical outcome can help inform discussion regarding the role of
      adjuvant chemotherapy in patients with resected colon cancer, such as those with
      stage II colon cancer in which the benefit of adjuvant therapy is controversial
      or those with stage III colon cancer who may have a lower risk of recurrence and
      less absolute benefit from oxaliplatin therapy. This article summarizes the data
      surrounding the development, validation, and clinical and economic utility of the
      Oncotype DX((r)) colon cancer assay, a multigene expression assay validated to
      independently predict recurrence risk in patients with stage II and III colon
      cancer beyond traditional factors. 

PMID- 25770398
TI  - Overcoming the polyethylene glycol dilemma via pathological environment-sensitive
      change of the surface property of nanoparticles for cellular entry.
AB  - Modification with polyethylene glycol (PEG) is currently considered an important
      strategy for anti-cancer drug delivery, because PEGylated-nanoparticles would be
      effectively delivered to tumor tissue by enhanced permeation and retention
      effects. However, PEGylation suppresses the cellular uptake of nanoparticles
      (NPs) to target cells (known as the PEG dilemma). Here, we propose a novel
      strategy, namely conferring a pathological environment-sensitive property of
      nanoparticles for overcoming the PEG dilemma. Specifically, although
      nanoparticles have an overall negative surface charge to avoid interactions with
      biogenic substances in blood circulation, inversion of surface charge (to
      positive) at the pH of the tumor microenvironment may allow the nanoparticles to
      be taken up by cancer cells. To prove this concept, charge-invertible
      nanoparticles modified with novel slightly acidic pH-sensitive peptide (SAPSP
      NPs) were developed. The negatively-charged SAPSP-NPs were delivered to tumor
      tissue, and were successfully taken up by cancer cells upon inversion of the
      surface charge to positive at intratumoral pH. SAPSP-NPs may serve as an
      alternative carrier to the PEGylated NP for anti-cancer drug delivery. 

PMID- 25770399
TI  - Developments in urologic oncology 'OncoForum': The best of 2014.
AB  - OBJECTIVE: To review the latest evidence on the oncologic urology of prostate,
      renal and bladder tumors, analyzing their impact on daily clinical practice and
      the future medium to long-term regimens. METHODS: We review the abstracts on
      prostate, renal and bladder cancer presented at the 2014 congresses (European
      Association of Urology, American Urological Association, American Society of
      Clinical Oncology and American Society for Radiation Oncology) that received the
      best evaluations by the OncoForum committee. RESULTS: The committee considered
      the following messages important: cytoreductive nephrectomy followed by treatment
      with a tyrosine-kinase inhibitor can significantly increase the overall survival
      of patients with metastatic renal cancer; for advanced bladder cancer, early
      adjuvant chemotherapy after cystectomy is preferable because it significantly
      increases progression-free survival; and several studies have shown that
      multiparametric magnetic resonance imaging and fusion imaging improve the
      diagnosis of prostate cancer and provide greater possibilities for placing
      patients in the appropriate risk group in order to offer them the best treatment
      possible. The results of the PREVAIL study have demonstrated the efficacy of
      enzalutamide on the overall survival of men with castration-resistant prostate
      cancer and metastases, with no prior chemotherapy. The study also demonstrated
      the drug's favorable safety profile. CONCLUSIONS: Progress is continuing in renal
      and bladder cancer, improving the approach and clinical results with current
      therapeutic options. There is constant progress in castration-resistant prostate
      cancer; in 2014, prechemotherapy treatments were consolidated.

PMID- 25770400
TI  - Opportunity to increase life span in narrow QRS cardiac resynchronization therapy
      recipients by deactivating ventricular pacing: evidence from randomized
      controlled trials.
AB  - OBJECTIVES: This study examined the time course of clinical events in cardiac
      resynchronization therapy (CRT) trials. BACKGROUND: Recent randomized controlled
      trial results suggest that in heart failure with narrow QRS, biventricular pacing
      (CRT) may increase mortality. The authors proposed implant complications as the
      cause, rather than a progressive adverse physiological effect. METHODS: The study
      identified all trials comparing CRT with no CRT, which reported Kaplan-Meier
      curves in groups defined by QRS: narrow, non-left bundle branch block (LBBB)
      broad, and LBBB broad. For each trial, the change in life span every 3 months up
      to 3.5 years (the longest time for which data are available) was calculated and a
      power law was fitted, that is, ? time(n). RESULTS: Four trials (MADIT-CRT
      [Multicenter Automatic Defibrillator Implantation Trial-Cardiac Resynchronization
      Therapy], RAFT [Resynchronization-Defibrillation for Ambulatory Heart Failure
      Trial], REVERSE [REsynchronization reVErses Remodeling in Systolic left
      vEntricular dysfunction], and EchoCRT [Echocardiography Guided Cardiac
      Resynchronization Therapy]), totaling 4,717 patients, reported curves for
      mortality or heart failure-related hospitalization, or for mortality. In patients
      with LBBB broad QRS (within MADIT-CRT), life span gain increased in proportion to
      time(1.94). In contrast, in patients with non-LBBB broad QRS (within MADIT-CRT)
      and patients with narrow QRS (EchoCRT), life span was lost in proportion to
      time(1.92) and time,(1.96) respectively. Hospitalization-free survival showed
      similar patterns. CONCLUSIONS: The nonlinear growth of life span gained when a
      CRT device is implanted in patients with LBBB broad QRS is unfortunately mirrored
      by a similarly progressive loss in life span in narrow QRS heart failure. This
      suggests the culprit is a progressive physiological effect of pacing rather than
      implant complications. If these data are not sufficient, a randomized controlled
      trial of deactivating CRT in patients with narrow QRS may now be needed, with a
      primary endpoint of increasing survival.

PMID- 25770401
TI  - When is it appropriate to withdraw cardiac resynchronization therapy? Guesses and
      evidence.

PMID- 25770402
TI  - Gold standard in anticoagulation assessment of left ventricular assist device
      patients?: how about bronze.

PMID- 25770403
TI  - Echocardiographic Ramp test for continuous-flow left ventricular assist devices:
      do loading conditions matter?
AB  - OBJECTIVES: This study investigated whether continuous AI and/or elevated mean
      arterial pressure (MAP) were associated with false positive results for flow
      obstruction in echocardiographic ramp speed tests in patients with a continuous
      flow left ventricular assist device. BACKGROUND: Failure to reduce the left
      ventricular end-diastolic diameter (LVEDD) with increasing device speeds in a
      ramp test is predictive of pump obstruction. Aortic insufficiency (AI) or
      increased MAP can diminish the ability to unload the left ventricle. METHODS:
      LVEDD was plotted against device speed, and a linear function slope was
      calculated. A flat LVEDD slope (>=-0.16) was considered abnormal (suggestive of
      obstruction). Ramp test results were compared in patients with or without either
      AI or increased MAP at baseline speed, and receiver-operator characteristic (ROC)
      curves were constructed for predictors of device obstruction. Device thrombosis
      was confirmed by direct visualization of clot at explantation or on inspection by
      the manufacturer. RESULTS: Of 78 ramp tests (55 patients), 36 were abnormal (18
      true positive, 18 false positive), and 42 were normal (37 true negative, 5 false
      negative). In patients with AI, LVEDD slope was -0.14 +/- 0.17, which was
      consistent with device obstruction (vs. -0.25 +/- 0.11 in patients without AI; p
      < 0.001), despite no difference in mean lactate dehydrogenase concentration
      between the 2 groups (1,301 +/- 1,651 U/l vs. 1,354 +/- 1,365 U/l; p = 0.91).
      Area under the ROC curve (AUC) for LVEDD slope was 0.76 and improved to 0.88
      after removal of patients with AI from the study. LVEDD slope in patients with
      MAP >=85 mm Hg was similar to that for device obstruction (-0.18 +/- 0.07) and
      was abnormal in 6 of the 12 ramp tests performed. Combining LVEDD slope with
      lactate dehydrogenase concentration increased the AUC to 0.96 as an indicator of
      device obstruction. CONCLUSIONS: Abnormal loading conditions due to AI or
      elevated MAP may result in false positive ramp tests.

PMID- 25770404
TI  - Anti-factor Xa and activated partial thromboplastin time measurements for heparin
      monitoring in mechanical circulatory support.
AB  - OBJECTIVES: This study investigated the relationship between anti-factor Xa (anti
      FXa) and activated partial thromboplastin time (aPTT) for monitoring intravenous
      unfractionated heparin (IV-UFH) in patients with continuous-flow left ventricular
      assist devices (CF-LVADs). BACKGROUND: CF-LVADs have become mainstream therapy
      for patients with advanced heart failure. Thromboembolic events, device
      thrombosis, and bleeding continue to be a challenge with this technology.
      Adequate anticoagulation is required to prevent these adverse events. METHODS: A
      prospective study of consecutive patients implanted with a CF-LVAD was conducted.
      Paired samples were considered concordant if aPTT values fell into expected
      ranges for subtherapeutic, therapeutic, and supratherapeutic anti-FXa levels.
      Heparin dosing was on the basis of anti-Xa levels. RESULTS: A total of 340 paired
      values from 38 patients were evaluated. Anti-FXa and aPTT were discordant in 253
      samples (74.4%), with a high degree of variability in aPTT for any given anti-FXa
      level (r(2) = 0.57). Results were discordant in 104 samples (63.8%) from patients
      undergoing bridging therapy with warfarin and in 149 samples (84.2%) from
      patients with device obstruction and/or hemolysis (p < 0.001). The most common
      pattern of discordance was a supratherapeutic aPTT value despite a therapeutic
      anti-FXa level (49.1% for bridging vs. 75.8% for device obstruction and/or
      hemolysis; p < 0.001). CONCLUSIONS: Levels of aPTT were disproportionately
      prolonged relative to the corresponding anti-FXa levels in CF-LVAD patients,
      particularly those with device obstruction. Hemolysis and warfarin administration
      may falsely elevate aPTT, resulting in overestimation of heparin concentration
      and under-anticoagulation. Use of aPTT and anti-FXa to guide heparin therapy may
      lead to different estimates of heparin concentration in the same patient.

PMID- 25770405
TI  - Gastrointestinal bleeding in recipients of the HeartWare Ventricular Assist
      System.
AB  - OBJECTIVES: This study evaluated gastrointestinal bleeding (GIB) in patients
      receiving the HeartWare HVAD System (HeartWare Inc., Framingham, Massachusetts)
      in the pivotal BTT (Bridge to Transplant) trial and under the continued access
      protocol (CAP). BACKGROUND: GIB has become a significant problem for recipients
      of continuous flow device left ventricular assist devices (CF-LVAD). The need for
      anticoagulation and antiplatelet therapies complicates the management of GIB.
      METHODS: Bleeding events from 382 patients with advanced heart failure (140
      patients enrolled in the BTT trial, and an additional 242 CAP patients) were
      analyzed. Post-implant anticoagulation consisted of heparin followed by warfarin
      at a target international normalized ratio of 2 to 3. Acetylsalicylic acid was
      recommended at 81 to 325 mg. RESULTS: Overall, 59 of 382 (15.4%) patients
      experienced 108 GIB events (0.27 events per patient year). Mean time to first
      bleed was 273.1 days and 86.1% of events occurred beyond 30 days. Freedom from
      GIB was 84.1% at 1 year. Median international normalized ratio at the time of
      first bleed was 2.4 +/- 1.4. The most common etiology of bleeding identified was
      arteriovenous malformation and the most common site was the small intestine.
      Repeat bleeding was infrequent, though GIB patients required more readmissions
      and developed nondevice infections more frequently. No patients required surgical
      intervention and no deaths directly related to GIB occurred. CONCLUSIONS:
      Recipients of the HeartWare Ventricular Assist Device System had an incidence of
      0.27 GIB/patient year with a freedom from GIB of 84.1% at 1 year. All patients
      with GIB events were managed with medical and endoscopic therapies, although 31%
      of patients experienced a recurrence of GIB. No surgical intervention was
      required. GIB did not impact survival. (Evaluation of the HeartWare Left
      Ventricular Assist Device for the Treatment of Advanced Heart Failure [ADVANCE];
      NCT00751972).

PMID- 25770406
TI  - Left ventricular assist devices ramp studies: truth or consequences?

PMID- 25770407
TI  - Phrenic nerve stimulation for central sleep apnea: wiping out apnea or whipping
      the muscles?

PMID- 25770408
TI  - Phrenic nerve stimulation for the treatment of central sleep apnea.
AB  - OBJECTIVES: The aim of this study was to evaluate chronic, transvenous,
      unilateral phrenic nerve stimulation to treat central sleep apnea (CSA) in a
      prospective, multicenter, nonrandomized study. BACKGROUND: CSA occurs
      predominantly in patients with heart failure and increases the risk for morbidity
      and mortality. Established therapies for CSA are lacking, and those available are
      limited by poor patient adherence. METHODS: Fifty-seven patients with CSA
      underwent baseline polysomnography followed by transvenous phrenic nerve
      stimulation system implantation and follow-up. Feasibility was assessed by
      implantation success rate and therapy delivery. Safety was evaluated by
      monitoring of device- and procedure-related adverse events. Efficacy was
      evaluated by changes in the apnea-hypopnea index at 3 months. Quality of life at
      6 months was evaluated using a sleepiness questionnaire, patient global
      assessment, and, in patients with heart failure at baseline, the Minnesota Living
      With Heart Failure Questionnaire. RESULTS: The study met its primary end point,
      demonstrating a 55% reduction in apnea-hypopnea index from baseline to 3 months
      (49.5 +/- 14.6 episodes/h vs. 22.4 +/- 13.6 episodes/h of sleep; p < 0.0001; 95%
      confidence interval for change: -32.3 to -21.9). Central apnea index,
      oxygenation, and arousals significantly improved. Favorable effects on quality of
      life and sleepiness were noted. In patients with heart failure, the Minnesota
      Living With Heart Failure Questionnaire score significantly improved. Device- or
      procedure-related serious adverse events occurred in 26% of patients through 6
      months post therapy initiation, predominantly due to lead repositioning early in
      the study. Therapy was well tolerated. Efficacy was maintained at 6 months.
      CONCLUSIONS: Transvenous, unilateral phrenic nerve stimulation appears safe and
      effective for treating CSA. These findings should be confirmed in a prospective,
      randomized, controlled trial. (Chronic Evaluation of Respicardia Therapy;
      NCT01124370).

PMID- 25770409
TI  - Left atrial decompression pump for severe heart failure with preserved ejection
      fraction: theoretical and clinical considerations.
AB  - OBJECTIVES: The purpose of this study was to provide insight into the potential
      for left atrium (LA) to aortic mechanical circulatory support as a treatment for
      patients with heart failure with preserved ejection fraction (HFpEF). BACKGROUND:
      Although HFpEF arises from different etiologies, 1 hallmark of all forms of this
      syndrome is a small or minimally-dilated left ventricle (LV). Consequently, the
      use of traditional mechanical circulatory support in end-stage patients has been
      difficult. In contrast, HFpEF is also characterized by a large LA. METHODS:
      Hemodynamic characteristics of 4 distinct HFpEF phenotypes were characterized
      from the published data: 1) hypertrophic cardiomyopathies; 2) infiltrative
      diseases; 3) nonhypertrophic HFpEF; and 4) HFpEF with common cardiovascular
      comorbidities (e.g., hypertension). Employing a previously-described
      cardiovascular simulation, the effects of a low-flow, micropump-based LA
      decompression device were modeled. The effect of sourcing blood from the LV
      versus the LA was compared. RESULTS: For all HFpEF phenotypes, mechanical
      circulatory support significantly increased cardiac output, provided a mild
      increase in blood pressure, and markedly reduced pulmonary and LA pressures. LV
      sourcing of blood reduced LV end-systolic volume into a range likely to induce
      suction. With LA sourcing, however, LV end-systolic volume increased compared
      with baseline. Due to pre-existing LA enlargement, LA volumes remained
      sufficiently elevated, thus minimizing the risk of suction. CONCLUSIONS: This
      theoretical analysis suggests that a strategy involving pumping blood from the LA
      to the arterial system may provide a viable option for end-stage HFpEF. Special
      considerations apply to each of the 4 types of HFpEF phenotypes described.
      Finally, an HFpEF-specific clinical profile scoring system (such as that of
      INTERMACS [Interagency Registry for Mechanically Assisted Circulatory Support])
      would aid in the selection of patients with the appropriate risk-benefit ratio
      for implantation of an active pump.

PMID- 25770410
TI  - The Heartmate Risk Score predicts morbidity and mortality in unselected left
      ventricular assist device recipients and risk stratifies INTERMACS class 1
      patients.
AB  - OBJECTIVES: This study evaluated the Heartmate Risk Score (HMRS) and its
      potential benefits in clinical practice. BACKGROUND: The HMRS has been shown to
      correlate with mortality in the cohort of patients enrolled in the Heartmate II
      trials, but its validity in unselected, "real world" populations remains unclear.
      METHODS: This study identified a cohort of 269 consecutive patients who received
      a Heartmate II left ventricular assist device at our institution, the Barnes
      Jewish Hospital in St. Louis, Missouri, between June 2005 and June 2013. Ninety
      day and 2-year mortality rates, as well as frequency of several morbid events,
      were compared by retrospectively assigned HMRS category groups. The analysis was
      repeated within the subgroup of INTERMACS (Interagency Registry for Mechanically
      Assisted Circulatory Support) class 1 patients. RESULTS: Receiver operating curve
      analysis showed that the HMRS correlated with 90-day mortality with an area under
      the curve of 0.70. Stratification in low, mid, and high HMRS groups identified
      patients with increasing hazard of 90-day mortality, increasing long-term
      mortality, increasing rate of gastrointestinal bleeding events, and increasing
      median number of days spent in the hospital in the first year post implant.
      Within INTERMACS class 1 patients, those in the highest HMRS group were found to
      have a relative risk of 90-day mortality 5.7 times higher than those in the
      lowest HMRS group (39.1% vs. 6.9%, p = 0.029). CONCLUSIONS: HMRS is a valid
      clinical tool to stratify risk of morbidity and mortality after implant of
      Heartmate II devices in unselected patients and can be used to predict short-term
      mortality risk in INTERMACS class 1 patients.

PMID- 25770411
TI  - Characterization of free thiol variants of an IgG1 by reversed phase ultra high
      pressure liquid chromatography coupled with mass spectrometry.
AB  - RP-HPLC has been demonstrated as a powerful tool to study antibody free thiol and
      disulfide variants. Recently, the introduction of UHPLC columns with wide pore
      size (300A) and small particle size (1.7MUm) offered the opportunity to further
      improve the separation of such variants. This paper describes a systematic
      evaluation of stationary phases, operating parameters, and mobile phases for a
      UHPLC based method to separate free thiol variants of a recombinant monoclonal
      antibody (referred as mAb A), targeting high resolution, high throughput and
      improved recovery. Among the four different stationary phases evaluated, UHPLC
      diphenyl columns were found to provide the best separation. Using an optimized
      UHPLC method, free thiol variants of mAb A were separated in 5min. Importantly,
      the UHPLC method revealed minor variants that had coeluted in an HPLC based
      method, and the UHPLC method is also applicable as a platform method for
      characterization of other mAbs as well. Furthermore, an on-line UHPLC-MS method
      was developed to characterize the separated variants, and this method can
      streamline the characterization of fully assembled monoclonal and bispecific
      therapeutic antibodies.

PMID- 25770412
TI  - Pharmacokinetics, bioavailability, and metabolism of Notoginsenoside Fc in rats
      by liquid chromatography/electrospray ionization tandem mass spectrometry.
AB  - Notoginsenoside Fc (NGFc) is a protopanaxadiol-type (PPD-type) saponin from Panax
      notoginseng, which has perfect anti-platelet aggregatory effect. However, its
      pharmacokinetics and metabolism in vivo remain unknown. In this study, a simple
      and sensitive liquid chromatography/electrospray ionization tandem mass
      spectrometry (LC-MS/MS) method was first developed for the determination of NGFc
      in rat plasma. After methanol-mediated protein precipitation, separation was
      achieved on a C18 column with MS detection operated in negative SRM mode at m/z
      604.56->m/z 783.90 and m/z 799.93->m/z 637.64 for NGFc and IS, respectively. The
      assay was linear over the concentration range (r>0.995) with the LLOQ of
      0.002MUg/ml. The intra- and inter-day precisions (R.S.D.) were 2.45-12.36% and
      3.67-14.22%, respectively; whereas accuracy ranged from (R.R.) 93.90% to 99.41%.
      The extraction recovery, stability, and matrix effect were within the acceptable
      limits. The validated LC-MS/MS method was successfully applied to the pre
      clinical pharmacokinetic studies of NGFc in rat. After oral and intravenous
      administration, NGFc showed dose-independent pharmacokinetic behaviors with a
      t1/2 of >22h and its oral bioavailability was 0.10-0.14%. In addition, a total of
      10 metabolites were detected and structurally characterized by UPLC-Q/TOF-MS
      technique, which suggested that deglycosylation was the major metabolic pathway
      for NGFc in rats.

PMID- 25770413
TI  - Simultaneous determination of propofol and its glucuronide in whole blood by
      liquid chromatography-electrospray tandem mass spectrometry and the influence of
      sample storage conditions on the reliability of the test results.
AB  - Propofol (2,6-diisopropylphenol) is commonly used as an anaesthetic agent but is
      also abused for recreational purposes. Several cases of fatalities involving self
      administered propofol have been reported. For rapid quantification of propofol
      and propofol beta-d-glucuronide (propofol G) in clinical and forensic cases, an
      ultra-performance liquid chromatography-tandem mass spectrometry method using
      pneumatically assisted electrospray ionisation has been developed. The technique
      has been validated on both ante-mortem and post-mortem human whole blood. The
      proteins in the blood samples were removed by the addition of a mixture of
      methanol and acetonitrile, and the extract was cleaned up by solid phase
      extraction. The extract was concentrated in dimethyl sulphoxide. The system was
      calibrated using matrix-matched calibrants combined with isotope dilution. The
      lower limits of quantification were 0.01 and 0.02mg/L for propofol and 0.02 and
      0.04mg/L for propofol G in ante-mortem and post-mortem whole blood, respectively.
      The relative intra-laboratory reproducibility standard deviation was less than
      10% at concentrations of 0.2mg/L or higher. The mean true extraction recovery was
      85% for propofol and 81% for propofol G. The trueness of the propofol
      determination expressed as the relative bias of the test results was within +/-6%
      at concentration levels of 0.01-8.5mg/L. Propofol was less stable in blood
      stabilised with a citrate-EDTA-fluoride mixture than in blood stabilised with an
      oxalate-fluoride mixture. The stability was lower at -20 degrees C than at 5
      degrees C and -80 degrees C. Propofol G did not show instability under the
      storage conditions tested.

PMID- 25770414
TI  - Therapeutic drug monitoring of carbamazepine and its metabolite in children from
      dried blood spots using liquid chromatography and tandem mass spectrometry.
AB  - Carbamazepine (CBZ) is a first-line drug for the treatment of different forms of
      epilepsy and the first choice drug for trigeminal neuralgia. CBZ is metabolized
      in the liver by oxidation into carbamazepine-10,11-epoxide (CBZE), its major
      metabolite which is equipotent and known to contribute to the pharmacological
      activity of CBZ. The aim of the present study was to develop and validate a
      reliable, selective and sensitive liquid chromatography-tandem mass spectrometry
      method for the simultaneous quantification of CBZ and its active metabolite in
      dried blood spots (DBS). The extraction process was carried out from DBS using
      methanol-water-formic acid (80:20:0.1, v/v/v). Chromatographic elution was
      achieved by using a linear gradient with a mobile phase consisting of
      acetonitrile-water-0.1% formic acid at a flow rate of 0.50mL/min. The method was
      linear over the range 1-40mg/L and 0.25-20mg/L for CBZ and CBZE, respectively.
      The limit of quantification was 0.75mg/L and 0.25mg/L for CBZ and CBZE. Intra-day
      and inter-day assay precisions were found to be lower than 5.13%, 6.46% and
      11.76%, 4.72% with mean percentage accuracies of 102.1%, 97.5% and 99.2%, 97.8%
      for CBZ and CBZE. We successfully applied the method for determining DBS finger
      prick samples in paediatric patients and confirmed the results with
      concentrations measured in matched plasma samples. This novel approach allows
      quantification of CBZ and its metabolite from only one 3.2mm DBS disc by LC-MS/MS
      thus combining advantages of DBS technique and LC-MS/MS in clinical practice.

PMID- 25770415
TI  - Determination of carnitine and acylcarnitines in human urine by means of
      microextraction in packed sorbent and hydrophilic interaction chromatography
      ultra-high-performance liquid chromatography-tandem mass spectrometry.
AB  - A method using semi-automatic microextraction by packed sorbent (eVol(r)-MEPS)
      and hydrophilic interaction chromatography-ultra-high-performance liquid
      chromatography-tandem mass spectrometry (HILIC-UHPLC-MS/MS) was described for the
      simultaneous determination of carnitine and acylcarnitines in human urine. The
      optimal conditions of MEPS extraction were obtained using C2 of M1 (C8+SCX) phase
      as a sorbent. Chromatographic separation of the analytes was achieved within
      2.5min on Acquity UPLC BEH HILIC column using a gradient elution program with
      water containing 5mM ammonium acetate and acetonitrile as the mobile phase. The
      detection was performed on a triple-quadrupole tandem mass spectrometer in a
      positive ion mode via electrospray ionization (ESI). The linearity of the
      calibration curves for all compounds was found over a range from 0.1ng/mL to
      500ng/mL. The method afforded satisfactory results in terms of sensitivity,
      specificity, precision, accuracy, recovery as well as stability of the analyte
      under various conditions. The method was used successfully for determination of
      carnitine and acylcarnitines in human urine.

PMID- 25770417
TI  - Occupation and other risk factors for injury among enlisted U.S. Army Soldiers.
AB  - OBJECTIVE: To investigate injury risk associated with occupation and occupational
      physical demand levels among U.S. Army Soldiers. STUDY DESIGN: Retrospective
      cohort study. METHODS: Personal characteristics, physical fitness, military
      occupational specialty (MOS), and injury data were obtained by survey from
      Soldiers in an Army light infantry brigade (n = 2101). Odds ratios (OR) and 95%
      confidence intervals (95% CI) from a multivariate analysis assessing injury risk
      were calculated. RESULTS: Injury incidence for the prior 12 months was 43%.
      Physical fitness and behavioral factors associated with injury risk included age
      21-29 (OR [age 21-29/age <= 20] = 1.37, 95% CI 1.00-1.90), BMI 27.5-29.9 (high
      overweight) (OR high-overweight/normal = 1.62, 95% CI 1.20-2.18); BMI >29.9
      (obese) (OR obese/normal = 1.73, 95% CI 1.23-2.44), cigarette smoking (OR
      Smoker/Nonsmoker = 1.34, 95% CI 1.11-1.63), and poor APFT two mile run
      performance (OR (Q4/Q1) = 1.61, 95% CI 1.19-2.19). Higher risk of injury was
      associated with some MOSs (OR (Chemical, Explosives & Ammunition/Infantry) =
      2.82, 95% CI 1.19-6.68; OR (Armor/Infantry) = 1.53, 95% CI 1.13-2.07).
      CONCLUSION: This study identified a number of potentially modifiable risk factors
      for injuries including: maintenance of healthy weight, improved aerobic
      endurance, and reduction in smoking. Results also indicate certain Army
      occupations may be at higher risk of injury. Further investigation into reasons
      for their higher risk is warranted.

PMID- 25770418
TI  - Evolutionary analysis of Tembusu virus: evidence for the emergence of a dominant
      genotype.
AB  - We recently identified Tembusu virus (TMUV) as a causative agent of duck
      infectious disease, which has spread in China since 2010. A recent study has
      indicated a potential case of human infection by TMUV, highlighting the need for
      further study of TMUV, especially its evolution. Because no information exists
      regarding the evolution of TMUV, we conducted comprehensive phylogenetic analyses
      using the largest collection of complete open reading frame (ORF) sequences of
      TMUV. Our results indicated that two lineages of viruses were associated with the
      2010 outbreak in China, and lineage II, in particular sublineage II-c, has arisen
      as the dominant lineage currently circulating. We inferred that the most recent
      common ancestor (MRCA) of this TMUV was emerged around 1996. Evidence of natural
      recombination was also detected in TMUV. Molecular adaptation analyses revealed
      that strong negative selection shaped the evolution of TMUV, while a number of
      codons subjected to positive pressure were also identified. Our study, for the
      first time, illustrated the evolutionary history and character of TMUV and will
      be helpful for vaccine and diagnostic development.

PMID- 25770416
TI  - Molecular chaperones and neuronal proteostasis.
AB  - Protein homeostasis (proteostasis) is essential for maintaining the functionality
      of the proteome. The disruption of proteostasis, due to genetic mutations or an
      age-related decline, leads to aberrantly folded proteins that typically lose
      their function. The accumulation of misfolded and aggregated protein is also
      cytotoxic and has been implicated in the pathogenesis of neurodegenerative
      diseases. Neurons have developed an intrinsic protein quality control network, of
      which molecular chaperones are an essential component. Molecular chaperones
      function to promote efficient folding and target misfolded proteins for refolding
      or degradation. Increasing molecular chaperone expression can suppress protein
      aggregation and toxicity in numerous models of neurodegenerative disease;
      therefore, molecular chaperones are considered exciting therapeutic targets.
      Furthermore, mutations in several chaperones cause inherited neurodegenerative
      diseases. In this review, we focus on the importance of molecular chaperones in
      neurodegenerative diseases, and discuss the advances in understanding their
      protective mechanisms. 

PMID- 25770419
TI  - A tailored exercise program versus general exercise for a subgroup of patients
      with low back pain and movement control impairment: A randomised controlled trial
      with one-year follow-up.
AB  - BACKGROUND: Exercise is an effective treatment for patients with sub-acute and
      chronic non-specific low back pain (NSLBP). Previous studies have shown that a
      subgroup of patients with NSLBP and movement control impairment (MCI) can be
      diagnosed with substantial reliability. However, which type of exercises are most
      beneficial to this subgroup is still unknown. OBJECTIVES: The effectiveness of a
      specific exercise treatment to improve movement control was tested in this study.
      METHODS: Using a multicentre randomised controlled trial (RCT), we compared
      exercises that targeted MCI (MC) with a general exercise (GE) treatment. After
      randomisation, patients in both groups n(MC = 52; GE = 54) were treated in eight
      private physiotherapy practices and five hospital outpatient physiotherapy
      centres. Follow-up measurements were taken at post-treatment, six months and 12
      months. The primary outcome measurement was the Patient Specific Function Scale
      (PSFS). RESULTS: PSFS showed no difference between groups after treatment, or at
      six months and 12 months. Secondary outcome analysis for pain and disability,
      measured with the Graded Chronic Pain scale and the Roland Morris Disability
      Questionnaire respectively, showed that a small improvement post-treatment
      levelled off over the long term. Both groups improved significantly (p < 0.001)
      over the course of one year. CONCLUSION: This study found no additional benefit
      of specific exercises targeting MCI.

PMID- 25770420
TI  - Short-term effects of high-intensity laser therapy on frozen shoulder: A
      prospective randomized control study.
AB  - BACKGROUND: Frozen shoulder, which is characterized by shoulder pain and
      limitation of the range of motion (ROM), is a common disorder. High-intensity
      laser therapy (HILT) was recently introduced in the musculoskeletal therapeutic
      field. OBJECTIVE: The objective of this study is to evaluate the clinical
      efficacy of HILT in patients with frozen shoulder. DESIGN: A prospective
      randomized controlled study. METHOD: Patients with frozen shoulder were randomly
      divided into 2 groups: a HILT group (n = 33) and a placebo group (n = 33). The
      treatment was administered 3 times per week on alternate days for 3 weeks. For
      all patients, the visual analog scale (VAS) for pain, VAS for satisfaction, and
      passive ROM were measured at baseline and 3, 8, and 12 weeks after the treatment.
      RESULTS: The HILT group had a lower pain VAS score at 3 weeks (3.2 +/- 1.7 vs.
      4.3 +/- 2.2, p = 0.033) and 8 weeks (2.2 +/- 2.0 vs. 3.4 +/- 2.7, p = 0.042),
      however, no statistically significant difference in the pain VAS was observed
      between the two groups at the final follow-up (12 weeks). No statistical
      difference in the ROM and the satisfaction VAS was observed between the 2 groups
      at serial follow-ups. CONCLUSIONS: In management of frozen shoulder, HILT
      provided significant pain relief at 3 and 8 weeks, but not at the final follow-up
      time point. HILT is a noninvasive adjuvant treatment that can reduce pain in
      frozen shoulders. Further study is needed in order to optimize the dose and
      duration of HILT.

PMID- 25770421
TI  - Sleep patterns and injury occurrence in elite Australian footballers.
AB  - OBJECTIVES: To examine the potential relationship between sleep duration and
      efficiency and injury incidence in elite Australian footballers. DESIGN:
      Prospective cohort study. METHODS: Australian footballers (n=22) from one AFL
      club were studied across the 2013 competitive season. In each week sleep duration
      and efficiency were recorded via actigraphy for 5 nights (the 3 nights preceding
      a game, the night of the game and the night after the game). Injury incidence was
      monitored and matched with sleep data: n=9 players suffered an injury that caused
      them to miss a game. Sleep in the week of the injury (T2) was compared to the
      average of the previous 2 weeks (T1). A two-way repeated measures ANOVA was used
      to determine any effect of sleep duration and efficiency on injury. Significance
      was accepted at p<0.05. RESULTS: Injury incidence was not significantly affected
      by sleep duration, sleep efficiency or a combination of these factors. Analysis
      of individual nights for T2 versus T1 also showed no differences in sleep quality
      or efficiency. However, a main effect for time was found for sleep duration and
      efficiency, with these being slightly, but significantly greater (p<0.05) at T2
      (437+/-61min and 82+/-7%) than T1 (414+/-64min and 79+/-7%). CONCLUSIONS: No
      significant effect of sleep duration and efficiency on injury occurrence was
      found in elite Australian footballers.

PMID- 25770422
TI  - A new enzyme involved in the control of the stereochemistry in the decalin
      formation during equisetin biosynthesis.
AB  - Tetramic acid containing a decalin ring such as equisetin and phomasetin is one
      of the characteristic scaffolds found in fungal bioactive secondary metabolites.
      Polyketide (PKS)-nonribosomal peptide synthetase (NRPS) hybrid enzyme is
      responsible for the synthesis of the polyketide scaffold conjugated with an amino
      acid. PKS-NRPS hybrid complex programs to create structural diversity in the
      polyketide backbone have begun to be investigated, yet mechanism of control of
      the stereochemistry in a decalin formation via a Diels-Alder cycloaddition
      remains uncertain. Here, we demonstrate that fsa2, which showed no homology to
      genes encoding proteins of known function, in the fsa cluster responsible for
      equisetin and fusarisetin A biosynthesis in Fusarium sp. FN080326, is involved in
      the control of stereochemistry in decalin formation via a Diels-Alder reaction in
      the equisetin biosynthetic pathway. 

PMID- 25770423
TI  - Activating PTEN by COX-2 inhibitors antagonizes radiation-induced AKT activation
      contributing to radiosensitization.
AB  - Radiotherapy is still one of the most effective nonsurgical treatments for many
      tumors. However, radioresistance remains a major impediment to radiotherapy.
      Although COX-2 inhibitors can induce radiosensitization, the underlying mechanism
      is not fully understood. In this study, we showed that COX-2 selective inhibitor
      celecoxib enhanced the radiation-induced inhibition of cell proliferation and
      apoptosis in HeLa and SACC-83 cells. Treatment with celecoxib alone
      dephosphorylated phosphatase and tensin homolog deleted on chromosome ten (PTEN),
      promoted PTEN membrane translocation or activation, and correspondingly
      dephosphorylated or inactivated protein kinase B (AKT). By contrast, treatment
      with radiation alone increased PTEN phosphorylation, inhibited PTEN membrane
      translocation and correspondingly activated AKT in the two cell lines. However,
      treatment with celecoxib or another COX-2 selective inhibitor (valdecoxib)
      completely blocked radiation-induced increase of PTEN phosphorylation, rescued
      radiation-induced decrease in PTEN membrane translocation, and correspondingly
      inactivated AKT. Moreover, celecoxib could also upregulate PTEN protein
      expression by downregulating Sp1 expression, thereby leading to the activation of
      PTEN transcription. Our results suggested that COX-2 inhibitors could enhance
      radiosensitization at least partially by activating PTEN to antagonize radiation
      induced AKT activation. 

PMID- 25770424
TI  - Temporo-spatial requirement of Smad4 in dentin formation.
AB  - The TGF-beta/BMP family plays an important role in multiple stages of tooth
      development. TGF-beta/BMP signaling is required for odontoblast differentiation
      and dentin formation; however, the precise molecular mechanisms underlying dentin
      formation remain unclear. To address the role of TGF-beta/BMP signaling in dentin
      formation, we analyzed mice in which Smad4, a key intracellular mediator of TGF
      beta/BMP signaling, was subjected to tissue-specific ablation under the control
      of Dspp, OC, or Col1a1 promoters. Three independent Smad4 conditional knockout
      mice exhibited various dentin defects in the crowns and roots of their molars
      depending on the transactivator. In all mutant molars, crown dentin thickness was
      thinner than that of the control. In addition, impaired dentin was found in the
      cervical region and root furcation area. Although the initial differentiation of
      odontoblasts was normal, odontoblast polarity abruptly decreased and the
      expression of Col1a1, OC, and Dspp was reduced in the odontoblasts of mutant
      molars. In Dspp-Cre-mediated Smad4 disruption mice, primary dentin formation was
      slightly delayed, while secondary dentin formation was severely affected in the
      cervical region of the molars. These results indicate that TGF-beta/BMP signaling
      is required for odontoblast maturation and dentin formation in a stage- and site
      dependent manner. 

PMID- 25770425
TI  - SOX9-mediated upregulation of LGR5 is important for glioblastoma tumorigenicity.
AB  - LGR5 plays an important role in the self-renewal of stem cells and is used as a
      marker identifying self-renewing stem cells in small intestine and hair
      follicles. Moreover, LGR5 has been reported to be overexpressed in several
      cancers. SOX9 is a transcription factor that plays a key role in development,
      differentiation and lineage commitment in various tissues. It has also been
      reported that SOX9 is overexpressed in a variety of cancers and contributes to
      their malignant phenotype. Here we show that LGR5 is required for the
      tumorigenicity of glioblastoma cells. We further show that SOX9 is upregulated in
      glioblastoma cells and directly enhances the expression of LGR5. We also
      demonstrate that knockdown of SOX9 suppresses the proliferation and
      tumorigenicity of glioblastoma cells. These results suggest that SOX9-mediated
      transcriptional regulation of LGR5 is critical for the tumorigenicity of
      glioblastoma cells. We speculate that the SOX9-LGR5 pathway could be a
      potentially promising target for the therapy of glioblastoma. 

PMID- 25770426
TI  - DIP1 plays an antiviral role against DCV infection in Drosophila melanogaster.
AB  - Disconnected Interacting Protein 1 (DIP1) is a dsRNA-binding protein that
      participates in a wide range of cellular processes. Whether DIP1 is involved in
      innate immunity remains unclear. Here, DIP1 was found to play an antiviral role
      in S2 cells. Its antiviral action is specific for DCV infection and not for DXV
      infection. dip1 mutant flies are hypersensitive to DCV infection. The increased
      mortality in dip1 mutant flies is associated with the accumulation of DCV
      positive-stranded RNAs in vivo. This study demonstrated that dip1 is a novel
      antiviral gene that restricts DCV replication in vitro and in vivo.

PMID- 25770427
TI  - Functional analysis of the N-terminal region of endolysin Lyb5 encoded by
      Lactobacillus fermentum bacteriophage phiPYB5.
AB  - Lactobacillus fermentum temperate bacteriophage phiPYB5 uses endolysin Lyb5 and
      holin Hyb5 to burst the host cell. Previous results showed that expression of
      Lyb5 in Escherichia coli caused host cell lysis slowly, leading us to suppose
      that Lyb5 could pass the cytoplasmic membrane partly. In this work, the function
      of a putative signal peptide (SPLyb5) at the N-terminal of Lyb5 was investigated.
      In E. coli, the cell adopted a spherical shape during induction of Lyb5 protein,
      while morphological changes were not observed during expression of the SPLyb5
      truncation, indicating that the SPLyb5 motif may serve as a functional signal
      peptide. However, SPLyb5 was not proteolytically cleaved at the predicted site
      during the translocation of Lyb5, and the expressed Lyb5 protein appeared in the
      cytoplasm, cytoplasmic membrane and periplasm fractions with the same molecular
      mass. Similar results were obtained using Lactococcus lactis as a host to express
      Lyb5. These results indicated that SPLyb5 could direct Lyb5 to the periplasm in a
      membrane-tethered form, and then release it as a soluble active enzyme into the
      periplasm. In addition, SPLyb5 could also drive the fused NucleaseB protein to
      the extracytoplasm environment in E. coli as well as in L. lactis. We proposed
      that in Gram-negative and Gram-positive hosts SPLyb5 acted as a signal-anchor
      release domain, which was firstly identified here by experimental evidences in
      lactic acid bacteria phages. The application of signal-anchor-release domain for
      endolysin export in bacteriophages infecting Gram-positive and Gram-negative
      hosts was discussed. 

PMID- 25770428
TI  - Prevalence and characterization of Campylobacter jejuni from chicken meat sold in
      French retail outlets.
AB  - Campylobacter was detected in 76% of broiler meat products collected in retail
      outlets during a monitoring plan carried out in France throughout 2009.
      Campylobacter jejuni was the most prevalent species (64.7% of products being
      contaminated). The 175 C. jejuni isolates collected were characterized. MLST
      typing results confirmed substantial genetic diversity as the 175 C. jejuni
      isolates generated 76 sequence types (STs). The ST-21, ST-45 and ST-464 complexes
      predominated accounting for 43% of all isolates. A class-specific PCR to screen
      the sialylated lipooligosaccharide (LOS) locus classes A, B and C showed that
      50.3% of the C. jejuni isolates harbored sialylated LOS. The antimicrobial
      resistance profiles established using a subset of 97 isolates showed that
      resistance to tetracycline was the most common (53.6%), followed with
      ciprofloxacin and nalidixic acid (32.9%, and 32.0% respectively). All the tested
      isolates were susceptible to erythromycin, chloramphenicol and gentamicin. Clear
      associations were demonstrated between certain clonal complexes and LOS locus
      classes and between certain clonal complexes and antimicrobial resistance. This
      work paints a representative picture of C. jejuni isolated from poultry products
      circulating in France, providing data on STs, LOS locus classes and antibiotic
      resistance profiles in isolates recovered from products directly available to the
      consumer. 

PMID- 25770429
TI  - Bacterial community dynamics and metabolite changes in myeolchi-aekjeot, a Korean
      traditional fermented fish sauce, during fermentation.
AB  - Myeolchi-aekjeot (MA) is a Korean traditional fish sauce, made by fermenting
      salted [approximately 25% (w/v)] anchovies. Three sets of MA samples, S-MA, M-MA,
      and L-MA, were prepared using small (5-8 cm), medium (8-10 cm), and large (10-13
      cm) anchovies, respectively, and their bacterial communities and metabolites were
      investigated for 280 days. Bacterial community analysis using pyrosequencing
      revealed that, in S-MA, the initially dominant genera, including Phychrobacter,
      Photobacterium, and Vibrio, disappeared rapidly and Salinivibrio, Staphylococcus,
      and Tetragenococcus/Halanaerobium appeared sequentially as the major populations.
      In contrast, in M-MA and L-MA, the initially dominant genera were maintained
      relatively well during the early fermentation period, but eventually
      Tetragenococcus became predominant without the growth of Halanaerobium. The
      changes in the bacterial community occurred more quickly in MA prepared with
      smaller anchovies than in those prepared with larger anchovies. Metabolite
      analysis using (1)H NMR showed that amino acids, glycerol, acetate, and lactate
      rapidly increased in all MA samples during the early fermentation period. Amino
      acids increased more quickly and then decreased after reaching their maximum
      level in S-MA, while they increased continually until the end of fermentation in
      L-MA. This suggests that the complete fermentation of L-MA may require more time
      than that for S-MA. A correlative analysis between bacterial communities and
      metabolites revealed that the increase in acetate, butyrate, and putrescine in S
      MA was associated with the growth of Halanaerobium, which may be a useful
      indicator of anchovy sauce quality.

PMID- 25770430
TI  - Antimicrobial resistance of non-typhoidal Salmonella isolates from egg layer
      flocks and egg shells.
AB  - This study was conducted to examine the antimicrobial resistance (AMR) of
      Salmonella spp. isolated from commercial caged layer flocks in New South Wales
      and South Australia. All Salmonella isolates (n=145) were subjected to phenotypic
      and genotypic characterisation of AMR and carriage of integrons. The majority of
      Salmonella isolates (91.72%) were susceptible to all antimicrobials tested in
      this study. Limited resistance was observed to amoxicillin and ampicillin
      (5.51%), tetracycline (4.13%), cephalothin (2.06%) and trimethoprim (0.68%). None
      of the isolates were resistant to cefotaxime, ceftiofur, ciprofloxacin,
      chloramphenicol, gentamycin, neomycin or streptomycin. A low frequency of
      Salmonella isolates (4.83%) harboured antimicrobial resistance genes and a class
      1 integron. The most commonly detected AMR genes among the Salmonella isolates
      were blaTEM (2.07%), tet A (1.38%) and dhfrV (0.69%). Overall, Salmonella
      enterica isolates exhibited a low frequency of AMR and represent a minimal public
      health risk associated with the emergence of multidrug resistant Salmonella spp.
      from the Australian layer industry. 

PMID- 25770431
TI  - Fishing area and fish size as risk factors of Anisakis infection in sardines
      (Sardina pilchardus) from Iberian waters, southwestern Europe.
AB  - The sardine (Sardina pilchardus) is a fish commonly consumed and appreciated in
      many countries, although they are more likely to be eaten fresh in western
      Mediterranean countries such as Spain, Portugal, France or Italy. A molecular
      epidemiological survey of sardines from 5 fishing areas of the Spanish
      Mediterranean (Malaga, southern Spain) and Atlantic coasts (southern: Cadiz and
      Isla Cristina; northern: A Coruna and Ondarroa) was carried out to determine the
      presence of Anisakis spp. larvae. The highest prevalence of these larvae was
      observed in fish from A Coruna (28.3%), followed by Ondarroa (5%) and Cadiz
      (2.5%). No Anisakis larvae were found in fish from Malaga and Isla Cristina.
      Three Anisakis genotypes were identified: Anisakis simplex sensu stricto,
      Anisakis pegreffii and a hybrid genotype between these two species. A. pegreffii
      was the most prevalent species in A Coruna (71% of larvae). Only three Anisakis
      larvae (9% collected larvae) were located in the musculature of sardines: two
      were identified as A. pegreffii while the other was a hybrid genotype. Sardine
      infection was associated with fishing area and fish length/weight (length and
      weight were strongly correlated; Pearson's correlation 0.82; p<0.001). Risk
      factor multivariate analysis showed that the risk of infection increases 1.6
      times for every additional cm in the length of the sardines from the same fishing
      area. Comparison of fish of equal length showed that in sardines from A Coruna
      the risk of parasitization is 11.5 times higher than in those from other fishing
      areas. Although the risk of infection by Anisakis through consumption of sardines
      is generally low due to the low epidemiological parameter values (prevalence 10%,
      mean intensity 1.7 (range 1-5) and mean abundance 0.17), as larger fish are more
      heavily parasitized, there is an increased risk of infection by Anisakis through
      consumption of large sardines which are raw or have undergone insufficient
      treatment (undercooked, smoked, marinated, salted, pickled, freezing,...). 

PMID- 25770432
TI  - Quantification and characterization of microbial biofilm community attached on
      the surface of fermentation vessels used in green table olive processing.
AB  - The aim of the present study was the quantification of biofilm formed on the
      surface of plastic vessels used in Spanish-style green olive fermentation and the
      characterization of the biofilm community by means of molecular fingerprinting.
      Fermentation vessels previously used in green olive processing were subjected to
      sampling at three different locations, two on the side and one on the bottom of
      the vessel. Prior to sampling, two cleaning treatments were applied to the
      containers, including (a) washing with hot tap water (60  degrees C) and
      household detergent (treatment A) and (b) washing with hot tap water, household
      detergent and bleach (treatment B). Population (expressed as log CFU/cm(2)) of
      total viable counts (TVC), lactic acid bacteria (LAB) and yeasts were enumerated
      by standard plating. Bulk cells (whole colonies) from agar plates were isolated
      for further characterization by PCR-DGGE. Results showed that regardless of the
      cleaning treatment no significant differences were observed between the different
      sampling locations in the vessel. The initial microbial population before
      cleaning ranged between 3.0-4.5 log CFU/cm(2) for LAB and 4.0-4.6 log CFU/cm(2)
      for yeasts. Cleaning treatments exhibited the highest effect on LAB that were
      recovered at 1.5 log CFU/cm(2) after treatment A and 0.2 log CFU/cm(2) after
      treatment B, whereas yeasts were recovered at approximately 1.9 log CFU/cm(2)
      even after treatment B. High diversity of yeasts was observed between the
      different treatments and sampling spots. The most abundant species recovered
      belonged to Candida genus, while Wickerhamomyces anomalus, Debaryomyces hansenii
      and Pichia guilliermondii were frequently detected. Among LAB, Lactobacillus
      pentosus was the most abundant species present on the abiotic surface of the
      vessels.

PMID- 25770433
TI  - Risk factors for e-cigarette, conventional cigarette, and dual use in German
      adolescents: a cohort study.
AB  - OBJECTIVE: Little is known about risk factors that are associated with e
      cigarette use in adolescents. METHODS: Multilevel mixed-effects regressions were
      performed to assess the relationship between factors that might be associated
      with e-cigarette, conventional cigarette and dual use in a cohort of 2693 German
      adolescents (mean age=12.5 years; SD=0.6). Risk factors were assessed in October
      2010 and life time e-cigarette and conventional cigarette use were assessed 26
      months later. RESULTS: Use of e-cigarettes as well as use of conventional
      cigarette and dual use were associated with higher sensation seeking scores, and
      higher odds of having friends and parents who smoke conventional cigarettes, with
      conventional cigarette use additionally with male gender, being older, having
      higher odds of siblings who smoke conventional cigarettes, and less likely for
      adolescents who attend a Gymnasium, secondary school with a strong emphasis on
      academic learning. The use of conventional cigarettes at baseline did not predict
      e-cigarette use at follow-up. Lifetime prevalence of e-cigarette use was 4.7%, of
      conventional cigarette use 18.4%. A quarter of e-cigarette users (23.8%) never
      smoked a conventional cigarette. DISCUSSION: Data indicate that e-cigarette and
      conventional cigarette use share many but not all risk factors. E-cigarettes
      could counteract the process of denormalization of smoking.

PMID- 25770434
TI  - The associations between overweight, weight change and health related quality of
      life: Longitudinal data from the Stockholm Public Health Cohort 2002-2010.
AB  - OBJECTIVE: Cross-sectional studies have shown that people with obesity and
      overweight report lower health related quality of life (HRQoL). With a lack of
      longitudinal studies, this study aims to assess the association between eight
      year weight change and HRQoL measured by the EQ-5D instrument and to investigate
      whether the association differs with regard to baseline body mass index (BMI).
      METHOD: A population-based survey was conducted among a random sample of 31,182
      individuals from Stockholm County aged 18-84years in 2002 and reassessed in 2010
      and supplemented by record linkage with regional and national registers.
      Multivariate Poisson regression and linear regression were conducted with
      adjustments for socio-demographic and health-related variables and baseline BMI
      category as effect modifier for the association between weight change and HRQoL.
      RESULTS: Individuals with overweight and obesity respectively have 0.014 and
      0.039 lower EQ-5D indexes compared to those being normal weight. Over the eight
      year follow-up, 17.6% gained moderately (>=5% body weight) and 13.9% gained
      heavily (>=10% body weight) in weight. In the fully adjusted analysis, heavy
      weight gain was associated with a significantly lower overall EQ-5D index and an
      increased risk of reporting impairment in all but one EQ-5D dimensions
      irrespective of baseline BMI category. Weight reduction had no significant
      preventive effect. CONCLUSION: Next to obesity status itself, weight gain leads
      to impairment in HRQoL irrespective of BMI category at baseline while eight year
      weight loss seems not to have the reversed effect on HRQoL, emphasizing the
      importance of primary prevention of weight gain.

PMID- 25770435
TI  - Healthy excessive weight in Portuguese women 4 years after delivery of a
      liveborn.
AB  - OBJECTIVE: To quantify the prevalence of healthy excessive weight and
      determinants of metabolic profile, considering women's reproductive life.
      METHODS: We evaluated 1847 mothers of a birth cohort assembled after delivery and
      reevaluated 4years later. A healthy profile was defined as the absence of
      hypertension, diabetes, dyslipidemia, C-reactive protein <3mg/l and being below
      the second tertile of HOMA-IR. Adjusted odds ratios (OR) and confidence intervals
      (95% CI) were computed using multinomial logistic regression, taking women with
      normal BMI as the reference category of the outcome. RESULTS: Four years after
      delivery, 47% of women had normal BMI, 33% were overweight and 20% obese. In each
      BMI class, 61%, 33% and 12% presented a healthy metabolic profile, respectively.
      Family history of CVD/cardiometabolic risk factors was associated with a higher
      probability of obesity with a not healthy metabolic profile (OR=1.39 95% CI: 0.98
      1.98). Women who breastfed the enrolled child for >26weeks and practiced physical
      exercise were less likely to be obese and metabolically unhealthy (OR=0.39 95%
      CI: 0.23-0.68; OR=0.48 95% CI: 0.33-0.70, respectively), with no effect on
      healthy excessive weight. CONCLUSIONS: These results support the existence of a
      healthy excessive weight phenotype in women after motherhood, influenced by
      anthropometrics, genetic and lifestyles characteristics.

PMID- 25770436
TI  - Draft genome of agar-degrading marine bacterium Gilvimarinus agarilyticus JEA5.
AB  - Gilvimarinus agarilyticus JEA5, which effectively degrades agar, was isolated
      from the seawater of Jeju Island, Republic of Korea. Here, we report the draft
      genome sequence of G. agarilyticus JEA5 with a total genome size of 4,179,438bp
      from 2 scaffolds (21 contigs) with 53.15% G+C content. Various polysaccharidases
      including 11 predicted agarases were observed from the draft genome of G.
      agarilyticus JEA5. 

PMID- 25770437
TI  - Urban political ecologies of informal recyclers' health in Buenos Aires,
      Argentina.
AB  - Buenos Aires' informal recyclers (cartoneros) confront multiple health hazards in
      their work. Based in a survey with (n=397) informal recyclers, this study
      establishes that these workers experience uneven health landscapes as evidenced
      through their health outcomes, the social determinants of their health, and their
      living and working environments. I argue that the analytical framework of urban
      political ecology can provide insights to the ways that the urban environments
      where cartoneros live and work are socially-constructed phenomena, drawing on
      concepts of crisis, metabolism, and multi-scalar analyses. 

PMID- 25770438
TI  - Gallstone ileus without bilioenteric fistula years after bypass surgery for
      Crohn's disease. Case report and clues to etiology of a neglected cause of
      obstruction.
AB  - INTRODUCTION: Gallstone ileus is a very rare cause of bowel obstruction. Patients
      suffering from Crohn's disease are at increased risk of developing gallstone
      disease, especially when terminal ileum is involved. Gallstone ileus can occur,
      but etiology remains controversial. We report on a case of such a rare condition,
      illustrating etiology and treatments. PRESENTATION OF CASE: A patient with long
      standing Crohn's disease, who had undergone ileotransverse bypass for ileocaecal
      involvement 40 years before, presented with cramp-like abdominal pain. Imaging
      was consistent with a gallstone ileus with no evidence of bilioenteric fistulae.
      DISCUSSION: At surgery, we found gallstones stuck at the site of ileotransverse
      anastomosis. No bilioenteric fistulae were found. Due to disease progression,
      many enteric fistulae were found, requiring a massive bowel resection. The
      diverted segment may have been responsible of gallstone formation, and etiology
      is discussed. Recovery after surgery was uneventful, but the patient required
      continued nutritional support. CONCLUSION: Physicians dealing with Crohn's
      disease patients with bypassed segments should keep in mind, the increased risk
      of gallstone formation, in order to not overlook gallstone ileus. Early suspect
      and diagnosis may allow for less aggressive approaches. A diverted segment should
      always be removed, and long-term follow-up encouraged.

PMID- 25770440
TI  - Emerging desalination technologies for water treatment: a critical review.
AB  - In this paper, a review of emerging desalination technologies is presented.
      Several technologies for desalination of municipal and industrial wastewater have
      been proposed and evaluated, but only certain technologies have been
      commercialized or are close to commercialization. This review consists of
      membrane-based, thermal-based and alternative technologies. Membranes based on
      incorporation of nanoparticles, carbon nanotubes or graphene-based ones show
      promise as innovative desalination technologies with superior performance in
      terms of water permeability and salt rejection. However, only nanocomposite
      membranes have been commercialized while others are still under fundamental
      developmental stages. Among the thermal-based technologies, membrane distillation
      and adsorption desalination show the most promise for enhanced performance with
      the availability of a waste heat source. Several alternative technologies have
      also been developed recently; those based on capacitive deionization have shown
      considerable improvements in their salt removal capacity and feed water recovery.
      In the same category, microbial desalination cells have been shown to desalinate
      high salinity water without any external energy source, but to date, scale up of
      the process has not been methodically evaluated. In this paper, advantages and
      drawbacks of each technology is discussed along with a comparison of performance,
      water quality and energy consumption. 

PMID- 25770439
TI  - Neurological consequences of traumatic brain injuries in sports.
AB  - Traumatic brain injury (TBI) is common in boxing and other contact sports. The
      long term irreversible and progressive aftermath of TBI in boxers depicted as
      punch drunk syndrome was described almost a century ago and is now widely
      referred as chronic traumatic encephalopathy (CTE). The short term sequelae of
      acute brain injury including subdural haematoma and catastrophic brain injury may
      lead to death, whereas mild TBI, or concussion, causes functional disturbance and
      axonal injury rather than gross structural brain damage. Following concussion,
      symptoms such as dizziness, nausea, reduced attention, amnesia and headache tend
      to develop acutely but usually resolve within a week or two. Severe concussion
      can also lead to loss of consciousness. Despite the transient nature of the
      clinical symptoms, functional neuroimaging, electrophysiological,
      neuropsychological and neurochemical assessments indicate that the disturbance of
      concussion takes over a month to return to baseline and neuropathological
      evaluation shows that concussion-induced axonopathy may persist for years. The
      developing brains in children and adolescents are more susceptible to concussion
      than adult brain. The mechanism by which acute TBI may lead to the
      neurodegenerative process of CTE associated with tau hyperphosphorylation and the
      development of neurofibrillary tangles (NFTs) remains speculative. Focal tau
      positive NFTs and neurites in close proximity to focal axonal injury and foci of
      microhaemorrhage and the predilection of CTE-tau pathology for perivascular and
      subcortical regions suggest that acute TBI-related axonal injury, loss of
      microvascular integrity, breach of the blood brain barrier, resulting
      inflammatory cascade and microglia and astrocyte activation are likely to be the
      basis of the mechanistic link of TBI and CTE. This article provides an overview
      of the acute and long-term neurological consequences of TBI in sports. Clinical,
      neuropathological and the possible pathophysiological mechanisms are discussed.
      This article is part of a Special Issue entitled 'Traumatic Brain Injury'. 

PMID- 25770441
TI  - In situ observation of the growth of biofouling layer in osmotic membrane
      bioreactors by multiple fluorescence labeling and confocal laser scanning
      microscopy.
AB  - Since the concept of the osmotic membrane bioreactor (OMBR) was introduced in
      2008, it has attracted growing interests for its potential applications in
      wastewater treatment and reclamation; however, the fouling mechanisms of forward
      osmosis (FO) membrane especially the development of biofouling layer in the OMBR
      are not yet clear. Here, the fouled FO membranes were obtained from the OMBRs on
      days 3, 8 and 25 in sequence, and then the structure and growing rule of the
      biofouling layer formed on the FO membrane samples were in-situ characterized by
      multiple fluorescence labeling and confocal laser scanning microscopy (CLSM).
      CLSM images indicated that the variations in abundance and distribution of
      polysaccharides, proteins and microorganisms in the biofouling layer during the
      operation of OMBRs were significantly different. Before the 8th day, their
      biovolume dramatically increased. Subsequently, the biovolumes of beta-d
      glucopyranose polysaccharides and proteins continued increasing and leveled off
      after 8 days, respectively, while the biovolumes of alpha-d-glucopyranose
      polysaccharides and microorganisms decreased. Extracellular polymeric substances
      (EPS) played a significant role in the formation and growth of biofouling layer,
      while the microorganisms were seldom detected on the upper fouling layer after 3
      days. Based on the results obtained in this study, the growth of biofouling layer
      on the FO membrane surface in the OMBR could be divided into three stages.
      Initially, EPS was firstly deposited on the FO membrane surface, and then
      microorganisms associated with EPS located in the initial depositing layer to
      form clusters. After that, the dramatic increase of the clusters of EPS and
      microorganisms resulted in the quick growth of biofouling layer during the flux
      decline of the OMBR. However, when the water flux became stable in the OMBR, some
      microorganisms and EPS would be detached from the FO membrane surface.

PMID- 25770442
TI  - Influence of Al3+ addition on the flocculation and sedimentation of activated
      sludge: comparison of single and multiple dosing patterns.
AB  - In this study, the flocculation and sedimentation performance of activated sludge
      (AS) with single and multiple dosing of trivalent aluminum (Al(3+)) were studied.
      The AS samples were cultivated in sequencing batch reactors at 22  degrees C. The
      dosages of Al(3+) were 0.00, 0.125, 0.5, 1.0, and 1.5 meq/L for single dosing,
      and 0.1 meq/L for multiple dosing. Under single dosing conditions, as Al(3+)
      dosage increased, the zeta potential, total interaction energy, and effluent
      turbidity decreased, whereas the sludge volume index (SVI) increased, indicating
      that single Al(3+) dosing could enhance sludge flocculation, but deteriorate
      sedimentation. By comparison, adding an equal amount of Al(3+) through multiple
      dosing achieved a similar reduction in turbidity, but the zeta potential was
      higher, while the loosely bound extracellular polymeric substances (LB-EPS)
      content and SVI remarkably declined. Although the difference in the flocculation
      performances between the two dosing patterns was not significant, the underlying
      mechanisms were quite distinct: the interaction energy played a more important
      role under single dosing conditions, whereas multiple dosing was more effective
      in reducing the EPS content. Multiple dosing, which allows sufficient time for
      sludge restructuring and floc aggregation, could simultaneously optimize sludge
      flocculation and sedimentation.

PMID- 25770443
TI  - An integrated logit model for contamination event detection in water distribution
      systems.
AB  - The problem of contamination event detection in water distribution systems has
      become one of the most challenging research topics in water distribution systems
      analysis. Current attempts for event detection utilize a variety of approaches
      including statistical, heuristics, machine learning, and optimization methods.
      Several existing event detection systems share a common feature in which alarms
      are obtained separately for each of the water quality indicators. Unifying those
      single alarms from different indicators is usually performed by means of simple
      heuristics. A salient feature of the current developed approach is using a
      statistically oriented model for discrete choice prediction which is estimated
      using the maximum likelihood method for integrating the single alarms. The
      discrete choice model is jointly calibrated with other components of the event
      detection system framework in a training data set using genetic algorithms. The
      fusing process of each indicator probabilities, which is left out of focus in
      many existing event detection system models, is confirmed to be a crucial part of
      the system which could be modelled by exploiting a discrete choice model for
      improving its performance. The developed methodology is tested on real water
      quality data, showing improved performances in decreasing the number of false
      positive alarms and in its ability to detect events with higher probabilities,
      compared to previous studies. 

PMID- 25770444
TI  - The limitations of applying zero-valent iron technology in contaminants
      sequestration and the corresponding countermeasures: the development in zero
      valent iron technology in the last two decades (1994-2014).
AB  - Over the past 20 years, zero-valent iron (ZVI) has been extensively applied for
      the remediation/treatment of groundwater and wastewater contaminated with various
      organic and inorganic pollutants. Based on the intrinsic properties of ZVI and
      the reactions that occur in the process of contaminants sequestration by ZVI,
      this review summarizes the limitations of ZVI technology and the countermeasures
      developed in the past two decades (1994-2014). The major limitations of ZVI
      include low reactivity due to its intrinsic passive layer, narrow working pH,
      reactivity loss with time due to the precipitation of metal hydroxides and metal
      carbonates, low selectivity for the target contaminant especially under oxic
      conditions, limited efficacy for treatment of some refractory contaminants and
      passivity of ZVI arising from certain contaminants. The countermeasures can be
      divided into seven categories: pretreatment of pristine ZVI to remove passive
      layer, fabrication of nano-sized ZVI to increase the surface area, synthesis of
      ZVI-based bimetals taking advantage of the catalytic ability of the noble metal,
      employing physical methods to enhance the performance of ZVI, coupling ZVI with
      other adsorptive materials and chemically enhanced ZVI technology, as well as
      methods to recover the reactivity of aged ZVI. The key to improving the rate of
      contaminants removal by ZVI and broadening the applicable pH range is to enhance
      ZVI corrosion and to enhance the mass transfer of the reactants including oxygen
      and H(+) to the ZVI surface. The characteristics of the ideal technology are
      proposed and the future research needs for ZVI technology are suggested
      accordingly. 

PMID- 25770445
TI  - Dissolved oxygen stratification and response to thermal structure and long-term
      climate change in a large and deep subtropical reservoir (Lake Qiandaohu, China).
AB  - From January 2010 to March 2014, detailed depth profiles of water temperature,
      dissolved oxygen (DO), and chromophoric dissolved organic matter (CDOM) were
      collected at three sites in Lake Qiandaohu, a large, deep subtropical reservoir
      in China. Additionally, we assessed the changes in DO stratification over the
      past 61 years (1953-2013) based on our empirical models and long-term air
      temperature and transparency data. The DO concentration never fell below 2 mg/L,
      the critical value for anoxia, and the DO depth profiles were closely linked to
      the water temperature depth profiles. In the stable stratification period in
      summer and autumn, the significant increase in CDOM in the metalimnion explained
      the decrease in DO due to the oxygen consumed by CDOM. Well-developed oxygen
      stratification was detected at the three sites in spring, summer and autumn and
      was associated with thermal stratification. Oxycline depth was significantly
      negatively correlated with daily air temperature and thermocline thickness but
      significantly positively correlated with thermocline depth during the
      stratification weakness period (July-February). However, there were no
      significant correlations among these parameters during the stratification
      formation period (March-June). The increase of 1.67  degrees C in yearly average
      daily air temperature between 1980 and 2013 and the decrease of 0.78 m in Secchi
      disk depth caused a decrease of 1.65 m and 2.78 m in oxycline depth,
      respectively, facilitating oxygen stratification and decreasing water quality.
      Therefore, climate warming has had a substantial effect on water quality through
      changing the DO regime in Lake Qiandaohu.

PMID- 25770446
TI  - Kinetic modeling and energy efficiency of UV/H2O2 treatment of iodinated
      trihalomethanes.
AB  - Photodegradation of I-THMs including CHCl2I and CHI3 by the UV/H2O2 system was
      investigated in this study. CHCl2I and CHI3 react rapidly with hydroxyl radical
      (OH) produced by the UV/H2O2 system, with second-order rate constants of 8.0 *
      10(9) and 8.9 * 10(9) M(-1) s(-1), respectively. A fraction of CHCl2I could be
      completely mineralized within 15 min and the remaining fraction was mainly
      converted to formic acid (HCO2H). Cl(-) and I(-) were identified as the
      predominant end-products. No ClO3(-) was observed during the photodegradation
      process, while IO3(-) was detected but at less than 2% of the total liberated
      iodine species at the end of the reaction. The effects of pH, H2O2 dose, and
      matrix species such as humic acid (HA), HCO3(-), SO4(2-), Cl(-), NO3(-) on the
      photodegradation kinetics were evaluated. The steady-state kinetic model has been
      proven to successfully predict the destruction of CHCl2I and CHI3 by UV/H2O2 in
      different water matrices. On this basis, the kinetic model combined with
      electrical energy per order (EE/O) concept was applied to evaluate the efficiency
      of the photodegradation process and to optimize the H2O2 dose for different
      scenarios. The optimal H2O2 doses in deionized (DI) water, model natural water,
      and surface water are estimated at 5, 12, and 16 mg L(-1), respectively, which
      correspond to the lowest total energy consumption (EE/Ototal) of 0.2, 0.31, and
      0.45 kWhm(-3)order(-1).

PMID- 25770447
TI  - Associations of chemical tracers and faecal indicator bacteria in a tropical
      urban catchment.
AB  - Surface water contamination by human faecal wastes is a widespread hazard for
      human health. Faecal indicator bacteria (FIB) are the most widely used indicators
      to assess surface water quality but are less-human-specific and have the
      potential to survive longer and/or occur naturally in tropical areas. In this
      study, 13 wastewater chemicals (chloride, boron, orthosphophate, detergents as
      methylene blue active substances, cholesterol, cholestanol, coprostanol,
      diethylhexyl phthalate, caffeine, acetaminophen, ibuprofen, sucralose and
      saccharin) were investigated in order to evaluate tracers for human faecal and
      sewage contamination in tropical urban catchments. Surface water samples were
      collected at an hourly interval from sampling locations with distinct major land
      uses: high-density residential, low-density residential, commercial and
      industrial. Measured concentrations were analysed to investigate the association
      among indicators and tracers for each land-use category. Better correlations were
      found between different indicators and tracers in each land-use dataset than in
      the dataset for all land uses, which shows that land use is an important
      determinant of drain water quality. Data were further segregated based on the
      hourly FIB concentrations. There were better correlations between FIB and
      chemical tracers when FIB concentrations were higher. Therefore, sampling
      programs must be designed carefully to take the time of sampling and land use
      into account in order to effectively assess human faecal and sewage contamination
      in urban catchments. FIB is recommended as the first tier in assessment of
      surface water quality impairment and chemical tracers as the second tier.
      Acetaminophen and coprostanol are recommended as chemical tracers for high
      density residential areas, while chloride, coprostanol and caffeine are
      recommended for low-density residential areas. 

PMID- 25770448
TI  - Removal properties of human enteric viruses in a pilot-scale membrane bioreactor
      (MBR) process.
AB  - In order to evaluate removal properties of human enteric viruses from wastewater
      by a membrane bioreactor (MBR), influent, anoxic and oxic mixed liquor, and
      membrane effluent samples were collected in a pilot-scale anoxic-oxic MBR process
      for 16 months, and concentrations of enteroviruses, norovirus GII, and
      sapoviruses were determined by real-time PCR using murine norovirus as a process
      control. Mixed liquor samples were separated into liquid and solid phases by
      centrifugation, and viruses in the bulk solution and those associated with mixed
      liquor suspended solids (MLSS) were quantified. Enteroviruses, norovirus GII, and
      sapoviruses were detected in the influent throughout the sampling period
      (geometrical mean, 4.0, 3.1, and 4.4 log copies/mL, respectively). Enterovirus
      concentrations in the solid phase of mixed liquor were generally lower than those
      in the liquid phase, and the mean log reduction value between influent and anoxic
      mixed liquor was 0.40 log units. In contrast, norovirus GII and sapovirus
      concentrations in the solid phase were equal to or higher than those in the
      liquid phase, and higher log reduction values (1.3 and 1.1 log units,
      respectively) were observed between influent and anoxic mixed liquor. This
      suggested that enteroviruses were less associated with MLSS than norovirus GII
      and sapoviruses, resulting in lower enterovirus removal in the activated sludge
      process. Enteroviruses and norovirus GII were detected in the MBR effluent but
      sapoviruses were not in any effluent samples. When MLSS concentration was reduced
      to 50-60% of a normal operation level, passages of enteroviruses and norovirus
      GII through a PVDF microfiltration membrane were observed. Since rejection of
      viruses by the membrane was not related to trans-membrane pressure which was
      monitored as a parameter of membrane fouling, the results indicated that
      adsorption to MLSS plays an important role in virus removal by an MBR, and
      removal properties vary by viruses reflecting different adsorptive behavior to
      MLSS. Our observations suggested that sapoviruses are more associated with MLSS
      and removed more efficiently than enteroviruses and norovirus GII. 

PMID- 25770449
TI  - Geochemical markers of soil anthropogenic contaminants in polar scientific
      stations nearby (Antarctica, King George Island).
AB  - The organic contamination of Antarctic soils and terrestrial sediments from
      nearby of five polar scientific stations on King George Island (Antarctica) was
      investigated. Gas chromatography-mass spectrometry (GC-MS) was applied to find
      composition of dichloromethane extracts of soil and terrestrial sediments. The
      presence of geochemical markers, such as n-alkanes, steranes, pentacyclic
      triterpenoids, and alkyl PAHs, their distribution types, and values of their
      ratios indicates the predominating source of organic fossil fuels and products of
      their refining rather than from the natural Antarctic environment. Fossil fuel
      originated compounds well survived in conditions of Antarctic climate over long
      times thus enabling to characterize geochemical features of source fossil fuel
      identified as petroleum expelled from kerogen II of algal/bacterial origins
      deposited in sub-oxic conditions and being in the middle of catagenesis. Both
      microbial activity and water leaching play an important role in degradation of
      terrestrial oil spills in the Antarctica climate, and petroleum alteration occurs
      lowly over long periods of time. Synthetic anthropogenic compounds found in
      terrestrial Antarctica sediments included diisopropylnaphthalenes, products of
      their sulfonates degradation in paper combustion, and organophosporus compounds
      used as retardants and plasticizers. 

PMID- 25770450
TI  - Short-term spatial and temporal variability of disinfection by-product occurrence
      in small drinking water systems.
AB  - Disinfection by-products (DBPs) constitute a large family of compounds.
      Trihalomethanes and haloacetic acids are regulated in various countries, but most
      DBPs are not. Monitoring DBPs can be delicate, especially for small systems,
      because various factors influence their formation and speciation. Short-term
      variations of DBPs can be important and particularly difficult for small systems
      to handle because they require robust treatment and operation processes.
      According to our knowledge, for the first time, our study covers the short-term
      variability of regulated and non-regulated DBP occurrence in small systems in the
      summer. An intensive sampling program was carried out in six small systems in
      Canada. Systems in the provinces of Newfoundland and Labrador and Quebec were
      sampled daily at the water treatment plant and at six different locations along
      the distribution system. Five DBP families were studied: trihalomethanes,
      haloacetic acids, haloacetonitriles, halonitromethanes and haloketones. Results
      show that there were considerable variations in DBP levels from week to week
      during the month of study and even from day to day within the week. On a daily
      basis, DBP levels can fluctuate by 22% to 96%. Likewise, the large number of
      sampling locations served to observe DBP variations along the distribution
      system. Observations revealed some degradation and decomposition of non-regulated
      DBPs never before studied in small systems that are associated with the
      difficulty these systems experience in maintaining adequate levels of residual
      disinfectant. Finally, this study reveals that the short term temporal
      variability of DBPs is also influenced by spatial location along the distribution
      system. In the short term, DBP levels can fluctuate by 23% at the beginning of
      the system, compared to 40% at the end. Thus, spatial and temporal variations of
      DBPs in the short term may make it difficult to select representative locations
      and periods for DBP monitoring purposes in small systems. 

PMID- 25770451
TI  - A review and comparative analysis of European priority indices for noise action
      plans.
AB  - The European Union has provided in recent years (and is going to update) several
      tools to harmonise noise mapping methodologies through directives and guidelines.
      Unfortunately the same efforts have not been put in the harmonisation of
      approaches for Noise Action Plans, the effective instruments to manage noise
      impacts. As a consequence, each European Member State at national or even at
      local level defined its own methodology, usually considerably different one from
      the others. Nevertheless, the most common approach to deal with noise impact at a
      policy, economic and strategy level is the use of priority indices focused to
      highlight areas or buildings where mitigation actions are more advisable or
      urgent. The aim of the present research is to provide a review of the most used
      European priority indices and also to test some of them in a study area. The
      comparative analysis demonstrates that the method chosen for the prioritisation
      deeply affects the ranking of the areas where noise measures need to be realized.
      Some methods tend to give high priority to noise sensitive locations, others to
      high populated buildings, and others to the areas where noise levels are high.
      The study proves how much common approaches are needed also for Noise Action
      Plans to reach a coherent noise policy within European boundaries. 

PMID- 25770452
TI  - Mixing zone and drinking water intake dilution factor and wastewater generation
      distributions to enable probabilistic assessment of down-the-drain consumer
      product chemicals in the U.S.
AB  - Environmental exposure and associated ecological risk related to down-the-drain
      chemicals discharged by municipal wastewater treatment plants (WWTPs) are
      strongly influenced by in-stream dilution of receiving waters which varies by
      geography, flow conditions and upstream wastewater inputs. The iSTREEM(r) model
      (American Cleaning Institute, Washington D.C.) was utilized to determine
      probabilistic distributions for no decay and decay-based dilution factors in mean
      annual and low (7Q10) flow conditions. The dilution factors derived in this study
      are "combined" dilution factors which account for both hydrologic dilution and
      cumulative upstream effluent contributions that will differ depending on the rate
      of in-stream decay due to biodegradation, volatilization, sorption, etc. for the
      chemical being evaluated. The median dilution factors estimated in this study
      (based on various in-stream decay rates from zero decay to a 1h half-life) for
      WWTP mixing zones dominated by domestic wastewater flow ranged from 132 to 609 at
      mean flow and 5 to 25 at low flow, while median dilution factors at drinking
      water intakes (mean flow) ranged from 146 to 2*10(7) depending on the in-stream
      decay rate. WWTPs within the iSTREEM(r) model were used to generate a
      distribution of per capita wastewater generated in the U.S. The dilution factor
      and per capita wastewater generation distributions developed by this work can be
      used to conduct probabilistic exposure assessments for down-the-drain chemicals
      in influent wastewater, wastewater treatment plant mixing zones and at drinking
      water intakes in the conterminous U.S. In addition, evaluation of types and
      abundance of U.S. wastewater treatment processes provided insight into treatment
      trends and the flow volume treated by each type of process. Moreover, removal
      efficiencies of chemicals can differ by treatment type. Hence, the availability
      of distributions for per capita wastewater production, treatment type, and
      dilution factors at a national level provides a series of practical and powerful
      tools for building probabilistic exposure models. 

PMID- 25770453
TI  - Immunohistochemistry, histopathology, and biomarker studies of swertiamarin, a
      secoiridoid glycoside, prevents and protects streptozotocin-induced beta-cell
      damage in Wistar rat pancreas.
AB  - BACKGROUND: Diabetes mellitus is globally the major cause for metabolic syndrome
      in STZ-induced diabetic rats, leading to mortality. Treatment of diabetes by oral
      hypoglycemic agents causes adverse side effects and thus treatment with natural
      herbal drugs like swertiamarin is promising. Swertiamarin, an active compound
      isolated from Enicostemma littorale possesses antidiabetic activity and enhances
      beta cell regeneration which causes reversal of diabetes. OBJECTIVES: The present
      study aims at the following: (1) to evaluate antidiabetic, anti-hyperlipidaemic,
      activity of swertiamarin in Streptozotocin- induced diabetic rats using
      biomarkers. (2) To assess histopathological alterations in Pancreas, Liver,
      Kidney, and Heart of swertiamarin-treated STZ-induced diabetic rats and confirm
      cytoprotective activity of swertiamarin by Immunohistochemistry and morphometric
      investigations. METHODS: Diabetes was induced intraperitoneally in male Wistar
      rats by Streptozotocin (STZ 50 mg/kg). After STZ-induction, hyperglycemic rats
      were treated with doses of swertiamarin orally (15, 25, 50 mg/kg) each for 28
      days. Glibenclamide (2.5 mg/kg), a sulphonyl urea, was used as a standard drug.
      The glycemic control was measured by the biochemical parameter assays.
      Histopathology analysis of organs and immunohistochemistry of islets were carried
      out. RESULTS: Our study results showed that oral administration of swertiamarin
      at a dosage of 15, 25, 50 mg/kg bw for 28 days resulted in a significant (p <
      0.01) decrease in fasting blood glucose, HbA1c, TC, TG, LDL, and increased the
      levels of hemoglobin, plasma insulin, TP, body weight, and HDL levels
      significantly (p < 0.01) when compared to STZ-induced diabetic rats, as confirmed
      by immunohistochemical studies. The effect of swertiamarin on Carbohydrate
      metabolizing enzymes was investigated and found to have normal therapeutic
      activity. Histopathological studies of Pancreas of swertiamarin-treated diabetic
      rats showed regeneration of islets when compared to STZ-induced diabetic rats, as
      confirmed by immunohistochemical studies. CONCLUSION: Our research results
      clearly substantiate that swertiamarin possesses antihyperglycemic,
      antihyperlipidemic, cytoprotective, and immune reactivity and also a broad
      spectrum potential of treating diabetes and other complications related to
      diabetes and hence can be developed into a potent oral antidiabetic drug.

PMID- 25770454
TI  - Exposure to polychlorinated biphenyls and hexachlorobenzene, semen quality and
      testicular cancer risk.
AB  - PURPOSE: We carried out a case-control study to investigate the possible role of
      occupational and environmental exposure to endocrine disruptors in the onset of
      testicular cancer (TC). METHODS: We evaluated 125 TC patients and 103 controls.
      Seminal fluid examination and organochlorine analysis were performed in all
      subjects. Cases and controls were also interviewed using a structured
      questionnaire to collect demographic information, residence, andrological medical
      history and dietary information. RESULTS: We found that a higher level of
      reproductive tract birth defects was associated with a higher risk of TC. With
      regard to diet, cases reported a higher consumption of milk and dairy products
      than controls. Overall, there was a statistically significant increase in TC risk
      in cases with detectable values of total polychlorinated organic compounds
      against controls (14.4 vs. 1.0 %; p < 0.001). TC patients with detectable levels
      of organochlorines had lower mean semen parameters than those with undetectable
      levels, although this difference was not statistically significant. CONCLUSION:
      The International Agency for Research on Cancer recently included dioxin-like
      polychlorinated biphenyls (PCBs) in Group 1 of known human carcinogens. Our study
      confirmed and identified various risk factors for testicular cancer:
      cryptorchidism, consumption of milk and dairy products, parents' occupation and
      serum concentration of hexachlorobenzene and PCBs and, for the first time, we
      showed the correlation between semen quality and the serum concentration of these
      pollutants.

PMID- 25770455
TI  - Myocardial fat as a part of cardiac visceral adipose tissue: physiological and
      pathophysiological view.
AB  - Thoracic fat includes extra-pericardial (outside the visceral pericardium) and
      intra-pericardial (inside the visceral pericardium) adipose tissue. It is called
      ectopic adipose tissue although it is a normal anatomical structure. Intra
      pericardial adipose tissue, which is predominantly composed of epicardial and
      pericoronary adipose tissue, has a significant role in cardiovascular system
      function. It provides metabolic-mechanical support to the heart and blood vessels
      in physiological conditions, while it represents metabolic-cardiovascular risk in
      case of qualitative and quantitative structural changes in the tissue: it
      correlates with coronary atherosclerotic disease, left ventricular mass, left
      atrium enlargement and atrial fibrillation presence. In the last decade there has
      been mounting evidence of fat cells presence in the myocardium of healthy (non
      diseased) persons as well as in persons with both cardiovascular and non
      cardiovascular diseases. Thus, it is necessary to clarify the incidence,
      aetiology, physiological role of fat cells in the myocardium, as well as the
      clinical significance of pathological fatty infiltration of the myocardium. 

PMID- 25770456
TI  - Vaccination coverage of children with inflammatory bowel disease after an
      awareness campaign on the risk of infection.
AB  - BACKGROUND: Children with inflammatory bowel disease are at risk of vaccine
      preventable diseases mostly due to immunosuppressive drugs. AIM: To evaluate
      coverage after an awareness campaign informing patients, their parents and
      general practitioner about the vaccination schedule. METHODS: Vaccination
      coverage was firstly evaluated and followed by an awareness campaign on the risk
      of infection via postal mail. The trial is a case-control study on the same
      patients before and after the awareness campaign. Overall, 92 children were
      included. A questionnaire was then completed during a routine appointment to
      collect data including age at diagnosis, age at data collection, treatment
      history, and vaccination status. RESULTS: Vaccination rates significantly
      increased for vaccines against diphtheria-tetanus-poliomyelitis (92% vs. 100%),
      Haemophilus influenzae (88% vs. 98%), hepatitis B (52% vs. 71%), pneumococcus
      (36% vs. 57%), and meningococcus C (17% vs. 41%) (p<0.05). Children who were
      older at diagnosis were 1.26 times more likely to be up-to-date with a minimum
      vaccination schedule (diphtheria-tetanus-poliomyelitis, pertussis, H. influenzae,
      measles-mumps-rubella, tuberculosis) (p=0.002). CONCLUSION: Informing
      inflammatory bowel disease patients, their parents and general practitioner about
      the vaccination schedule via postal mail is easy, inexpensive, reproducible, and
      increases vaccination coverage. This method reinforces information on the risk of
      infection during routine visits.

PMID- 25770457
TI  - Oral contraceptive-induced hepatic sinusoidal dilatation.

PMID- 25770458
TI  - Selective fluorescent sensing of alpha-amanitin in serum using carbon quantum
      dots-embedded specificity determinant imprinted polymers.
AB  - alpha-amanitin could make patients die of acute liver failure within a short time
      if suitable treatment is not provided in a timely fashion. This paper
      demonstrates a new strategy for direct detection of alpha-amanitin in serum using
      carbon quantum dots-embedded specificity determinant imprinted polymers.
      According to the structure of alpha-amanitin, we selected a proper moiety of
      alpha-amanitin as specificity determinant to synthesize template to prepare the
      MIPs. The computer simulation was used to screen out acidic methacrylic acid
      (MAA) and basic 4-vinyl pyridine (4-Vpy) together as functional monomers, and the
      experiments further proved that synergistic interaction of MAA and 4-Vpy was
      beneficial to enhance the recognition capability of MIPs for alpha-amanitin.
      Moreover, the fluorescence intensity showed good linear correlations with the
      concentration of alpha-amanitin from 0.05 to 4.0MUgmL(-1). The detection limit
      for alpha-amanitin was 15ngmL(-1). The nanoparticles were employed to directly
      detect alpha-amanitin in serum without any pretreatment with recoveries of 97.8
      100.9%. 

PMID- 25770459
TI  - A fluorescence in situ hybridization (FISH) microfluidic platform for detection
      of HER2 amplification in cancer cells.
AB  - Over-expression/amplification of human epidermal growth factor receptors 2 (HER2)
      is a verified therapeutic biomarker for breast and gastric cancers. HER2 is also
      served as prognostic biomarker for gastric cancer because HER2 over-expression is
      associated with a 5-10% increase in cancer related death of gastric cancer.
      Cancer patients exhibiting HER2 over-expression can significantly improve their
      overall survival rates by taking the targeting drug Herceptin, which directly
      targets HER2. However, Herceptin has limited functions toward patients without
      HER2 over-expression and therefore it needs a highly specific and accurate
      detection method for diagnosis of HER2 over-expression. Currently, fluorescence
      in situ hybridization (FISH) technique is routinely employed to detect HER2
      amplification. However, it is a labor-intensive, time-consuming hybridization
      process and is relatively costly. Furthermore, well-trained personnel are
      required to operate the delicate and complicate process. More importantly, it may
      take 1-2 days for well-trained personnel to perform a whole FISH assay. Given
      these limitations, we developed a new, integrated microfluidic FISH system
      capable of automating the entire FISH protocol which could be performed within a
      shorter period of time when compared to traditional methods. The microfluidic
      FISH chip consisted of a microfluidic control module for transportation of small
      amounts of fluids and a hybridization module to perform the hybridization of DNA
      probes and cells/tissue samples. With this approach, the new microfluidic chip
      was capable of performing the whole FISH assay within 20h. Four cell lines, two
      for non-HER2 amplification and two for HER2 amplification, and two clinical
      tissue samples, one for non-HER2 amplification and another for HER2
      amplification, were used for verifications of the developed chip. Experimental
      data showed that there was no significant difference between the benchtop
      protocol and the chip-based protocol. Furthermore, the reagent consumption was
      greatly reduced (~70% reduction). Especially, only 2-MUl usage for FISH
      deoxyribonucleic acid (DNA) probe was used, which is five-fold reduction when
      compared with the traditional method. It is the first time that the entire FISH
      assay could be automated on a single chip by using tissue samples. The
      microfluidic system developed herein is therefore promising for rapid, automatic
      diagnosis of HER2-related diseases by detecting the HER2 gene with minimal
      consumption of samples and reagents and has a great potential for future
      pharmacogenetic diagnostics and therapy. 

PMID- 25770460
TI  - An electrochemical biosensor based on DNA tetrahedron/graphene composite film for
      highly sensitive detection of NADH.
AB  - Dihydronicotinamide adenine dinucleotide (NADH) is a major biomarker correlated
      with lethal diseases such as cancers and bacterial infection. Herein, we report a
      graphene-DNA tetrahedron-gold nanoparticle modified gold disk electrode for
      highly sensitive NADH detection. By assembling the DNA tetrahedron/graphene
      composite film on the gold disk electrode surface which prior harnessed
      electrochemical deposition of gold nanoparticles to enhance the effective surface
      area, the oxidation potential of NADH was substantially decreased to 0.28V (vs.
      Ag/AgCl) and surface fouling effects were successfully eliminated. Furthermore,
      the lower detection limit of NADH by the presented platform was reduced down to
      1fM, with an upper limit of 10pM. Both the regeneration and selectivity of
      composite film-modified electrode are investigated and proved to be robust. The
      novel sensor developed here could serve as a highly sensitive probe for NADH
      detection, which would further benefit the field of NADH related disease
      diagnostics. 

PMID- 25770461
TI  - Elevated phthalates' exposure in children with constitutional delay of growth and
      puberty.
AB  - BACKGROUND: Phthalates have been proven to be antiandrogenic, which may interfere
      with the timing of puberty. Children with Constitutional Delay of Growth and
      Puberty (CDGP) typically display short stature and pubertal delay. This study
      investigated whether phthalate's exposure was associated with CDGP, and evaluated
      the potential mediator role of testosterone. METHODS: In this case-control study,
      a total of 167 boys, including 57 boys with CDGP (cases) and 110 controls were
      enrolled. We measured six major phthalate metabolites in urine samples using high
      performance liquid chromatography and tandem mass spectrometry (LC-MS/MS). The
      serum testosterone level was determined by radioimmunoassay. RESULTS: Children in
      the CDGP group were determined to have significantly elevated urinary phthalates
      concentration compared with control subjects (total phthalates median: case,
      107.00 ng/ml; control, 62.22 ng/ml, p = 0.001). After adjustment for BMI and
      other confounding factors: mono-n-butyl phthalate (MBP), monoethyl phthalate
      (MEP) and total phthalate concentrations were significantly negatively associated
      with serum testosterone level (MBP: beta = -45.7, p = 0.017; MEP: beta = -31.6, p
      = 0.022; total phthalates: beta = -24.6, p = 0.011); MBP, MEP, mono (2
      ethylhexyl) phthalate (MEHP) and total phthalates were significantly associated
      with CDGP (odds ratio: MBP: 8.30, p = 0.002; MEP: 5.43, p = 0.002; MEHP: 3.83, p
      = 0.017; total phthalates: 9.09, p = 0.001). Serum testosterone level acted as a
      mediator of the association between phthalates' exposure and CDGP (p = 0.002)
      (proportion mediated: 34.4%). CONCLUSIONS: In this case-control study, elevated
      phthalates' level was detected in children with CDGP in Shanghai, China and
      phthalate level was associated with CDGP, which appeared to be mediated by
      circulating testosterone level.

PMID- 25770462
TI  - The mechanism and significance of synergistic induction of the expression of
      plasminogen activator inhibitor-1 by glucocorticoid and transforming growth
      factor beta in human ovarian cancer cells.
AB  - Plasminogen activator inhibitor-1 (PAI-1) plays a key role in tissue remodeling
      and tumor development by suppression of plasminogen activator function.
      Glucocorticoids (GCs) and transforming growth factor beta (TGF-beta) signal
      pathways cross-talk to regulate gene expression, but the mechanism is poorly
      understood. Here we investigated the mechanism and significance of co-regulation
      of PAI-1 by TGF-beta and dexamethasone (DEX), a synthetic glucocorticoid in
      ovarian cancer cells. We found that TGF-beta and DEX showed rapidly synergistic
      induction of PAI-1 expression, which contributed to the early pro-adhesion
      effects. The synergistic induction effect was accomplished by several signal
      pathways, including GC receptor (GR) pathway and TGF-beta-activated p38MAPK, ERK
      and Smad3 pathways. TGF-beta-activated p38MAPK and ERK pathways cross-talked with
      GR pathway to augment the expression of PAI-1 through enhancing DEX-induced GR
      phosphorylation at Ser211 in ovarian cancer cells. These findings reveal possible
      novel mechanisms by which TGF-beta pathways cooperatively cross-talk with GR
      pathway to regulate gene expression. 

PMID- 25770463
TI  - Which public and why deliberate?--A scoping review of public deliberation in
      public health and health policy research.
AB  - Deliberative methods are of increasing interest to public health researchers and
      policymakers. We systematically searched the peer-reviewed literature to identify
      public health and health policy research involving deliberative methods and
      report how deliberative methods have been used. We applied a taxonomy developed
      with reference to health policy and science and technology studies literatures to
      distinguish how deliberative methods engage different publics: citizens (ordinary
      people who are unfamiliar with the issues), consumers (those with relevant
      personal experience e.g. of illness) and advocates (those with technical
      expertise or partisan interests). We searched four databases for empirical
      studies in English published 1996-2013. This identified 78 articles reporting on
      62 distinct events from the UK, USA, Canada, Australasia, Europe, Israel, Asia
      and Africa. Ten different types of deliberative techniques were used to represent
      and capture the interests and preferences of different types of public. Citizens
      were typically directed to consider community interests and were treated as a
      resource to increase democratic legitimacy. Citizens were preferred in
      methodological studies (those focused on understanding the techniques). Consumers
      were directed to focus on personal preferences; thus convened not as a source of
      policy decisions, but of knowledge about what those affected by the issue would
      accept. Advocates-who are most commonly used as expert witnesses in juries-were
      sometimes engaged to deliberate with consumers or citizens. This almost always
      occurred in projects directly linked to policy processes. This suggests health
      policymakers may value deliberative methods as a way of understanding
      disagreement between perspectives. Overall however, the 'type' of public sought
      was often not explicit, and their role not specified. This review provides new
      insight into the heterogeneity and rising popularity of deliberative methods, and
      indicates a need for greater clarity regarding both the constitution of publics
      and the relative usefulness of different deliberative techniques. 

PMID- 25770464
TI  - Spider stimuli improve response inhibition.
AB  - Anxiety can have positive effects on some aspects of cognition and negative
      effects on others. The current study investigated whether task-relevant anxiety
      could improve people's ability to withhold responses in a response inhibition
      task. Sixty-seven university students completed a modified and an unmodified
      version of the Sustained Attention to Response Task (SART; Robertson, Manly,
      Andrade, Baddeley, & Yiend, 1997) and provided subjective measures of arousal and
      thoughts. Anxiety appeared to improve participants' ability to withhold
      responses. Further, participants' performance was consistent with a motor
      response inhibition perspective rather than a mind-wandering perspective of SART
      commission error performance. Errors of commission were associated with response
      times (speed-accuracy trade-off) as opposed to task-unrelated thoughts. Task
      related thoughts were associated with the speed-accuracy trade-off. Conversely
      task-unrelated thoughts showed an association with errors of omission, suggesting
      this SART metric could be an indicator of sustained attention. Further
      investigation of the role of thoughts in the SART is warranted. 

PMID- 25770465
TI  - Process development for scum to biodiesel conversion.
AB  - A novel process was developed for converting scum, a waste material from
      wastewater treatment facilities, to biodiesel. Scum is an oily waste that was
      skimmed from the surface of primary and secondary settling tanks in wastewater
      treatment plants. Currently scum is treated either by anaerobic digestion or
      landfilling which raised several environmental issues. The newly developed
      process used a six-step method to convert scum to biodiesel, a higher value
      product. A combination of acid washing and acid catalyzed esterification was
      developed to remove soap and impurities while converting free fatty acids to
      methyl esters. A glycerol washing was used to facilitate the separation of
      biodiesel and glycerin after base catalyzed transesterification. As a result, 70%
      of dried and filtered scum was converted to biodiesel which is equivalent to
      about 134,000 gallon biodiesel per year for the Saint Paul waste water treatment
      plant in Minnesota. 

PMID- 25770466
TI  - Influence of deflocculation on microwave disintegration and anaerobic
      biodegradability of waste activated sludge.
AB  - In the present study, the potential benefits of deflocculation on microwave
      pretreatment of waste activated sludge were investigated. Deflocculation in the
      absence of cell lysis was achieved through the removal of extra polymeric
      substances (EPS) by sodium citrate (0.1g sodium citrate/g suspended solids), and
      DNA was used as a marker for monitoring cell lysis. Subsequent microwave
      pretreatment yielded a chemical oxygen demand (COD) solubilisation of 31% and
      21%, suspended solids (SS) reduction of 37% and 22%, for deflocculated and
      flocculated sludge, respectively, with energy input of 14,000kJ/kg TS. When
      microwave pretreated sludge was subjected to anaerobic fermentation, greater
      accumulation of volatile fatty acid (860mg/L) was noticed in deflocculated
      sludge, indicating better hydrolysis. Among the samples subjected to BMP
      (Biochemical methane potential test), deflocculated microwave pretreated sludge
      showed better amenability towards anaerobic digestion with high methane
      production potential of 0.615L (gVS)(-1). 

PMID- 25770467
TI  - LCA of bioethanol and furfural production from vetiver.
AB  - In this study a prospective life cycle assessment of biorefinery system from
      vetiver leaves was carried out to know the environmental benefits of this system
      over conventional systems considering the geographical context of India. The
      composition of vetiver leaves from the experimental analysis revealed that
      vetiver is rich in cellulose (32.6%), hemicellulose (31.5%) and lignin (17.3%)
      that could be used as a feedstock for biorefinery. The comparative life cycle
      assessment results show that the carbon dioxide emission and fossil oil depletion
      could be reduced by 95% and 23% respectively in case of standalone bioethanol
      system, and 99% and 17% respectively in case of bioethanol and furfural system
      compared to that of conventional petrol and furfural systems. The sensitivity
      study indicates that the impact could be further reduced if vetiver biomass is
      used as a source of energy in biorefinery plant instead to the coal. 

PMID- 25770468
TI  - Solid-state anaerobic digestion of fungal pretreated Miscanthus sinensis
      harvested in two different seasons.
AB  - Solid-state anaerobic digestion of Miscanthus sinensis harvested in fall and
      spring was compared under different total solids contents and feedstock-to
      inoculum ratios. The highest specific methane yields reached 170-175LCH4/kg
      volatile solids for both harvest seasons. Miscanthus harvested in fall generated
      a 6% higher methane yield in average than miscanthus harvested in spring. Fungal
      pretreatment with Ceriporiopsis subvermispora decreased the lignin content of
      miscanthus harvested in spring by 25.7%, but there was no significant
      delignification observed for miscanthus harvested in fall. Fungal pretreatment of
      miscanthus harvested in spring increased the specific methane yield by 25%, but
      fungal pretreatment caused a slight methane yield reduction for miscanthus
      harvested in fall. Methane yields for miscanthus were comparable with those from
      other energy crops. 

PMID- 25770469
TI  - Study of novel pure culture HBCD-1, effectively degrading Hexabromocyclododecane,
      isolated from an anaerobic reactor.
AB  - In this study, two pure strains, named HBCD-1 and HBCD-2, were isolated from a
      continuous anaerobic reactor over 300-days acclimation, which processed high
      capability of biodegrading Hexabromocyclododecane. Both of the two strains
      degraded HBCD diastereomers in different extents, especially strain HBCD-1, which
      interestingly degraded alpha-HBCD effectively. All of the degrading results were
      well fitted with the first-order kinetics model. By morphological observation and
      16S rRNA gene sequence analysis, the strain HBCD-1 showed highest similarity with
      Achromobacter sp. Under the optimal culturing conditions of 30 degrees C, pH 7
      and the initial HBCD concentration of 500MUg/L, the biodegradation rate of HBCD-1
      reached 90% after 8days treatment. Moreover, during the biodegradation process by
      HBCD-1 strain, the concentration of bromide ion was lower than the theoretical
      value. Finally, 4 metabolites were determined by liquid chromatography-tandem
      mass spectrometry (LC-MS/MS), as well as a biodegradation pathway was proposed. 

PMID- 25770470
TI  - Long-term operation of a pilot scale anaerobic membrane bioreactor (AnMBR) for
      the treatment of municipal wastewater under psychrophilic conditions.
AB  - The performance of a pilot scale anaerobic membrane bioreactor (AnMBR),
      comprising an upflow anaerobic sludge blanket (UASB) reactor coupled to an
      external ultrafiltration membrane treating municipal wastewater at 18+/-2 degrees
      C, was evaluated over three years of stable operation. The reactor was inoculated
      with a mesophilic inoculum without acclimation. The AnMBR supported a tCOD
      removal efficiency of 87+/-1% at hydraulic retention time (HRT) of 7h, operating
      at a volumetric loading rate (VLR) of between 2 and 2.5kgtCOD/m(3)d, reaching
      effluent tCOD concentrations of 100-120mg/L and BOD5 concentrations of 35
      50mgO2/L. Specific methane yield varied from 0.18 to 0.23Nm(3)CH4/kgCODremoved
      depending on the recirculation between the membrane module and the UASB reactor.
      The permeate flow rate, using cycles of 15s backwash, 7.5min filtration, and
      continuous biogas sparging (40-60m/h), ranged from 10 to 14Lm(2)/h with trans
      membrane pressure (TMP) values of 400-550mbar. 

PMID- 25770471
TI  - Coproduction of xylose, lignosulfonate and ethanol from wheat straw.
AB  - A novel integrated process to coproduce xylose, lignosulfonate and ethanol from
      wheat straw was investigated. Firstly, wheat straw was treated by dilute sulfuric
      acid and xylose was recovered from its hydrolyzate. Its optimal conditions were
      1.0wt% sulfuric acid, 10% (w/v) wheat straw loading, 100 degrees C, and 2h. Then
      the acid treated wheat straw was treated by sulfomethylation reagent and its
      hydrolyzate containing lignosulfonate was directly recovered. Its optimal
      conditions were 150 degrees C, 15% (w/v) acid treated wheat straw loading, and
      5h. Finally, the two-step treated wheat straw was converted to ethanol through
      enzymatic hydrolysis and microbial fermentation. Under optimal conditions, 1kg
      wheat straw could produce 0.225kg xylose with 95% purity, 4.16kg hydrolyzate of
      sulfomethylation treatment containing 5.5% lignosulfonate, 0.183kg ethanol and
      0.05kg lignin residue. Compared to present technology, this process is a
      potential economically profitable wheat straw biorefinery. 

PMID- 25770472
TI  - Co-liquefaction of microalgae and lignocellulosic biomass in subcritical water.
AB  - This study investigated co-liquefaction of microalgae (Chlorella pyrenoidosa, CP)
      and lignocellulosic biomass (Rice husk, RH) in subcritical water for bio-oil
      production. The effects of liquefaction temperature (200-350 degrees C),
      residence time (10-90min), solid concentration (10-30wt.%) and mass ratio of
      CP/RH on product distribution were investigated. The results showed that the
      highest yield of bio-crude oils at the combination of 50% CP with 50% RH was
      obtained at 300 degrees C temperature, 60min residence time and 20wt.% solid
      concentration. The oil yields increased gradually with the increased mass ratio
      of CP/RH. The major compounds identified in bio-crude oils from hydrothermal
      liquefaction (HTL) of RH were cyclic oxygenates (20.62%), followed by esters,
      ketones and alcohols (17.19%). As for CP, the main components were straight &
      branched amides (28.38%). A synergistic interaction was observed between CP and
      RH during co-liquefaction, resulting in decreased acidity and nitrogen content of
      bio-crude oils. 

PMID- 25770473
TI  - A feasibility study on the bioconversion of CO2 and H2 to biomethane by gas
      sparging through polymeric membranes.
AB  - In this study, the potential of a pilot hollow-fiber membrane bioreactor for the
      conversion of H2 and CO2 to CH4 was evaluated. The system transformed 95% of H2
      and CO2 fed at a maximum loading rate of 40.2 [Formula: see text] and produced
      0.22m(3) of CH4 per m(3) of H2 fed at thermophilic conditions. H2 mass transfer
      to the liquid phase was identified as the limiting step for the conversion, and
      kLa values of 430h(-1) were reached in the bioreactor by sparging gas through the
      membrane module. A simulation showed that the bioreactor could upgrade biogas at
      a rate of 25m(3)/mR(3)d, increasing the CH4 concentration from 60 to 95%v. This
      proof-of-concept study verified that gas sparging through a membrane module can
      efficiently transfer H2 from gas to liquid phase and that the conversion of H2
      and CO2 to biomethane is feasible on a pilot scale at noteworthy load rates.

PMID- 25770474
TI  - Patient-derived xenograft models for pancreatic adenocarcinoma demonstrate
      retention of tumor morphology through incorporation of murine stromal elements.
AB  - Direct implantation of viable surgical specimens provides a representative
      preclinical platform in pancreatic adenocarcinoma. Patient-derived xenografts
      consistently demonstrate retained tumor morphology and genetic stability.
      However, the evolution of the tumor microenvironment over time remains poorly
      characterized in these models. This work specifically addresses the recruitment
      and incorporation of murine stromal elements into expanding patient-derived
      pancreatic adenocarcinoma xenografts, establishing the integration of murine
      cells into networks of invading cancer cells. In addition, we provide methods and
      observations in the establishment and maintenance of a patient-derived pancreatic
      adenocarcinoma xenograft model. A total of 25 histologically confirmed pancreatic
      adenocarcinoma specimens were implanted subcutaneously into nonobese diabetic
      severe combined immunodeficiency mice. Patient demographics, staging,
      pathological analysis, and outcomes were analyzed. After successful engraftment
      of tumors, histological and immunofluorescence analyses were performed on
      explanted tumors. Pancreatic adenocarcinoma specimens were successfully engrafted
      in 15 (60%) of 25 attempts. Successful engraftment does not appear to correlate
      with clinicopathologic factors or patient survival. Tumor morphology is conserved
      through multiple passages, and tumors retain metastatic potential. Interestingly,
      despite morphological similarity between passages, human stromal elements do not
      appear to expand with invading cancer cells. Rather, desmoplastic murine stroma
      dominates the xenograft microenvironment after the initial implantation.
      Recruitment of stromal elements in this manner to support and maintain tumor
      growth represents a novel avenue for investigation into tumor-stromal
      interactions.

PMID- 25770475
TI  - TNFalpha Regulates SIRT1 Cleavage during Ocular Autoimmune Disease.
AB  - Elevated tumor necrosis factor (TNF) alpha levels are associated with chronic
      autoimmune diseases in which effects of TNFalpha on immune cells are multiple and
      complex. Analysis of uveitis in mice exhibiting severe autoimmune inflammation,
      resulting in a destructive subtotal loss of photoreceptors, revealed the presence
      of high plasma levels of TNFalpha and a significant population of
      CD4(+)TNFalpha(+) cells in the periphery and the eye at peak disease
      (TNFalpha(hi)). We have shown previously by pharmacological activation that the
      deacetylase Sirtuin 1 (SIRT1) has an anti-inflammatory role in a less severe,
      TNFalpha(lo) model of uveitis. We now show that SIRT1 activation fails to
      clinically suppress severe TNFalpha(hi) disease, whereas glucocorticoid treatment
      is successful. TNFalpha has been reported to mediate cleavage and inactivation of
      SIRT1 during inflammation, and at peak disease we observed both full-length and
      cleaved SIRT1 in draining lymph node cells. In vivo systemic TNFalpha blockade
      suppressed severe ocular disease and restricted SIRT1 cleavage in the periphery,
      maintaining full-length active SIRT1 protein. When combining a suboptimal
      TNFalpha blockade with SIRT1 activation, a synergistic suppression of severe
      disease compared with TNFalpha blockade alone occurred. Our data suggest a new
      role for TNFalpha in exacerbating the severity of autoimmune disease by
      regulating SIRT1 cleavage in draining lymph node effector cells. SIRT1 activation
      may be effective as an adjunctive treatment for inflammatory conditions not fully
      controlled by TNFalpha inhibitors.

PMID- 25770476
TI  - The effectiveness of installing physical barriers for preventing railway suicides
      and accidents: evidence from Japan.
AB  - BACKGROUND: Installing physical barriers, such as platform screen doors (PSDs),
      on train platforms is considered to be one of the most effective measures to
      prevent railway suicide. However, there is little evidence on the effectiveness
      of such barriers. In particular, the effectiveness of half-height, as opposed to
      full-height, PSDs has never been assessed. METHODS: Using suicide and accident
      data between 2004 and 2014 provided by a major railway company in the Tokyo
      metropolitan area, this study examines whether the installation of half-height
      PSDs has contributed to the reduction of the incidents of fatal and non-fatal
      railway suicide. In addition, the study tests whether the installation of PSDs
      has resulted in the reduction of unintentional falls onto railway tracks.
      RESULTS: Our estimation using a Poisson regression model showed that the
      introduction of PSDs resulted in a decrease in the number of suicides by 76% (CI:
      33-93%). Yet, the installation of PSDs has not completely prevented suicide, as
      there were cases in which passengers climbed them over. As for unintentional
      accidents, no fall accidents occurred at stations with PSDs. LIMITATIONS: Our
      data come only from one train operator, and thus the generalizability of our
      results may be limited. We do not fully examine potential substitution effects.
      CONCLUSION: Platform screen doors are effective in reducing the number of railway
      suicides. However, half-height PSDs are less effective than the full-height PSDs
      in preventing intentional entry to the train tracks. Installation of PSDs is an
      extremely effective method to prevent fall accidents.

PMID- 25770477
TI  - Help-seeking, stigma and attitudes of people with and without a suicidal past. A
      comparison between a low and a high suicide rate country.
AB  - BACKGROUND: A significant proportion of suicidal persons do not seek help for
      their psychological problems. Psychological help-seeking is assumed to be a
      protective factor for suicide. However, different studies showed that negative
      attitudes and stigma related to help-seeking are major barriers to psychological
      help-seeking. These attitudes and stigma are not merely individual
      characteristics but they are also developed by and within society. The aim of
      this study is twofold. First, we investigate if persons with a suicidal past
      differ from people without a suicidal past with respect to help-seeking
      intentions, attitudes toward help-seeking, stigma and attitudes toward suicide.
      The second aim is to investigate if these attitudinal factors differ between
      people living in two regions with similar socio-economic characteristics but
      deviating suicide rates. METHOD: We defined high (Flemish Community of Belgium)
      and low (The Netherlands) suicide regions and drew a representative sample of the
      general Flemish and Dutch population between 18 and 65 years. Data were gathered
      by means of a postal questionnaire. Descriptive statistics are presented to
      compare people with and without suicidal past. Multiple logistic regressions were
      used to compare Flemish and Dutch participants with a suicidal past. RESULTS:
      Compared to people without a suicidal past, people with a suicidal past are less
      likely to seek professional and informal help, perceive more stigma, experience
      more self-stigma (only men) and shame (only women) when seeking help and have
      more accepting attitudes toward suicide. In comparison to their Dutch
      counterparts, Flemish people with a suicidal past have less often positive
      attitudes toward help-seeking, less intentions to seek professional and informal
      (only women) help and have less often received help for psychological problems
      (only men). LIMITATIONS: The main limitations are: the relatively low response
      rate; suicidal ideation was measured by retrospective self-report; and the
      research sample includes only participants between 18 and 65 years old.
      CONCLUSIONS: Having a suicidal past is associated with attitudinal and
      stigmatizing barriers toward help seeking and accepting attitudes toward suicide.
      Prevention strategies should therefore target people with a suicidal history with
      special attention for attitudes, self-stigma and feelings of shame related to
      help-seeking.

PMID- 25770478
TI  - What is the best tool for screening antenatal depression?
AB  - BACKGROUND: Antenatal depression (AD) can have devastating consequences. No
      existing scales are specifically designed to measure it. Common practice is to
      adapt scales originally developed for other circumstances. We designed this study
      to validate and determine the psychometric values for AD screening in Brazil.
      METHODS: We collected clinical and socio-demographic data in the second
      gestational trimester. The following instruments were also administered during
      that period: MINI-PLUS, EPDS, BDI and HAM-D. RESULTS: At the time of assessment,
      17.34% of the patients were depressed, and 31.98% met the diagnostic criteria for
      lifetime major depression. All instruments showed an area under the curve in a
      receiver operating characteristic analysis greater than 0.85, with the BDI
      achieving a 0.90 and being the best-performing screening instrument. A score >=11
      on the EPDS (81.58% sensitivity, 73.33% specificity), >=15 on the BDI (82.00%
      sensitivity, 84.26% specificity) and >=9 on the HAM-D (87.76% sensitivity, 74.60%
      specificity) revealed great dichotomy between depressed and non-depressed
      patients. Spearman's rank correlation coefficients (rho) among the scales had
      good values (EPDS vs. BDI 0.79; BDI vs. HAM-D 0.70, and EPDS vs. HAM-D 0.67).
      LIMITATIONS: This study was transversal, assessing only women in the second
      gestational trimester. Results may be applicable only to the Brazilian population
      since psychometric properties may vary with the population under study. Major
      depression can amplify somatic symptomatology, affecting depressive rating scale
      data. CONCLUSION: AD is highly prevalent in Brazil. To address the problem of
      under-recognition, physicians can use the EPDS, BDI and HAM-D to identify AD.

PMID- 25770479
TI  - Increased impulsivity as a vulnerability marker for bipolar disorder: evidence
      from self-report and experimental measures in two high-risk populations.
AB  - BACKGROUND: Heightened impulsivity has been suggested as a possible risk factor
      for bipolar disorder (BD). However, studies on high-risk populations are scarce
      and have mainly focused on individuals with a genetic risk. The present study
      investigated two high-risk samples for BD with regard to several aspects of the
      impulsivity construct. METHODS: Unaffected relatives of BD patients (genetically
      defined high-risk group, N=29) and participants scoring high on the Hypomanic
      Personality Scale (psychometrically defined high-risk sample, N=25) were being
      compared to respective control groups (N=27 and N=25) using a multi-method
      approach. Participants were accessed on the Barratt Impulsiveness Scale-11 (BIS
      11, trait impulsivity), the Stop Signal Task (response inhibition), and the
      Cambridge Gambling Task (impulsive behavior in decision-making processes).
      RESULTS: Both high-risk groups reported heightened impulsivity on the BIS-11, as
      well as impulsive decision-making, whereas no significant group differences in
      response inhibition were observed. LIMITATIONS: Limitations were the lack in
      specificity of the results for BD and the cross-sectional study design, which
      does not allow conclusions about the influence of impulsivity on the development
      of or resilience for BD in risk groups. CONCLUSIONS: Our findings support the
      assumption that increased trait impulsivity and impulsive decision-making are a
      vulnerability marker for and an endophenotype of BD.

PMID- 25770480
TI  - Social information processing following resection of the insular cortex.
AB  - The insula has been implicated in social cognition and empathy in several
      neuroimaging paradigms. Impairments in social information processing, including
      specific deficits in disgust recognition, have been described following isolated
      insular damage, although the evidence remains limited to a few case studies. The
      present study examines social cognition and empathy in a group of fifteen
      patients for whom the insula was removed as part of their epilepsy surgery. These
      patients were compared to a lesion-control group of 15 epileptic patients who had
      a surgery in the anterior temporal lobe that spared the insula, and to 20 healthy
      volunteers matched on age, sex, and education. Participants were assessed on an
      Emotion Recognition Task (ERT), the Reading the Mind in the Eyes test, and a self
      administered empathy questionnaire. Patients who underwent insular resection
      showed poorer ability to recognize facial expressions of emotions and had lower
      scores of perspective taking on the empathy questionnaire than healthy controls.
      Using results from healthy controls as normative data, emotion recognition
      deficits were more frequent in insular patients than in both other groups.
      Specific emotion analyses revealed impairments in fear recognition in both groups
      of patients, whereas happiness and surprise recognition was only impaired in
      patients with insular resection. There was no evidence for a deficit in disgust
      recognition. The findings suggest that unilateral damage to the operculo-insular
      region may be associated with subtle impairments in emotion recognition, and
      provide further clinical evidence of a role of the insula in empathic processes.
      However, the description of 15 consecutive cases of insula-damaged patients with
      no specific deficit in disgust recognition seriously challenges the assumptions,
      based on previous case reports, that the insula is specifically involved in
      disgust processing. 

PMID- 25770481
TI  - The underactive bladder: a new clinical concept?
AB  - Detrusor underactivity (DU) is an increasingly recognised cause of lower urinary
      tract symptoms in both men and women. There has been a lack of research into all
      aspects of this dysfunction, and as yet, no effective treatments exist. DU can be
      diagnosed at present only on the basis of an invasive urodynamic study. An
      international consensus group met at the International Consultation on
      Incontinence-Research Society and International Continence Society annual
      meetings in 2014 to consider the feasibility of developing a working definition
      of a symptom complex associated with DU. Drawing an analogy to detrusor
      overactivity (urodynamic diagnosis) and overactive bladder (symptom complex), the
      aim of this process is to help identify affected patients and facilitate further
      clinical and epidemiological research. PATIENT SUMMARY: Bladder underactivity is
      an underresearched but important cause of urinary symptoms in men and women. In
      this paper, an international expert group presents a working definition for the
      symptoms that characterise bladder underactivity, with the aim of facilitating
      further research in this area.

PMID- 25770482
TI  - Achieving Quality Assurance of Prostate Cancer Surgery During Reorganisation of
      Cancer Services.
AB  - BACKGROUND: National Health Service England recently oversaw a whole-scale
      reconfiguration of cancer services in London, UK, for a number of different
      cancer pathways. Centralisation of cancer surgery has occurred with prostate
      cancer (PCa) surgery only being commissioned at a single designated pelvic cancer
      surgical centre. This process has required surgeons to work in teams providing a
      hub-and-spoke model of care. OBJECTIVE: To report the extent to which the
      initiation of a quality assurance programme (QAP) can improve the quality of PCa
      surgical care during reorganisation of cancer services in London. DESIGN,
      SETTING, AND PARTICIPANTS: A pre- and postintervention study was initiated with
      732 men undergoing robot-assisted radical PCa surgery over a 3-yr period, 396 men
      before the introduction of the QAP and 336 afterwards. INTERVENTION: Image-based
      surgical planning of cancer surgery and monthly peer review of individual surgeon
      outcomes incorporating rating and assessment of edited surgical video clips.
      OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: We observed margin status
      (positive/negative), complication rate of surgery, 3-mo urinary continence, use
      of nerve-sparing surgery, and potency at 12 mo after surgery. Multivariable
      logistic regression modelling was used to compare outcomes before and after
      initiation of the QAP. Cox regression analysis was used to evaluate the return of
      potency over time. RESULTS AND LIMITATIONS: Demographics of patients undergoing
      surgery did not change following the reorganisation of cancer services. Patient
      reported 3-mo urinary continence improved following the initiation of the QAP,
      both in terms of requirement for incontinence pads (57% continent vs 67%
      continent; odds ratio [OR]: 2.19; 95% confidence interval [CI], 1.08-4.46;
      p=0.02) and International Consultation on Incontinence Questionnaire score (5.6
      vs 4.2; OR: 0.82; 95% CI, 0.70-0.95; p=0.009). Concurrently, use of nerve-sparing
      surgery increased significantly (OR: 2.99; 95% CI, 2.14-4.20; p<0.001) while
      margin status remained static. Potency at 12 mo increased significantly from 21%
      to 61% in those patients undergoing bilateral nerve-sparing surgery (hazard
      ratio: 3.58; 95% CI, 1.29-9.87; p=0.04). Interaction was noted between surgeon
      and 3-mo urinary continence. On regression analysis, incontinence scores improved
      significantly for all but one surgeon who had low incontinence rates at study
      initiation. CONCLUSIONS: The implementation of a QAP improved quality of care in
      terms of consistency of patient selection and outcomes of surgery during a period
      of major reorganisation of cancer services in London. The QAP framework presented
      could be adopted by other organisations providing complex surgical care across a
      large network of referring hospitals. PATIENT SUMMARY: The introduction of a
      quality assurance programme improved the quality of prostate cancer care in terms
      of consistency of patient selection and outcomes of surgery during a period of
      major reorganisation of cancer services.

PMID- 25770483
TI  - Keeping an Open Mind About Novel Concepts for Management of Prostate Cancer.

PMID- 25770485
TI  - Predicting Outcomes in Bladder Cancer: Are We Any Good and Could We Do Better?

PMID- 25770484
TI  - Urinary Incontinence and Erectile Dysfunction After Robotic Versus Open Radical
      Prostatectomy: A Prospective, Controlled, Nonrandomised Trial.
AB  - BACKGROUND: Robot-assisted laparoscopic radical prostatectomy (RALP) has become
      widely used without high-grade evidence of superiority regarding long-term
      clinical outcomes compared with open retropubic radical prostatectomy (RRP), the
      gold standard. OBJECTIVE: To compare patient-reported urinary incontinence and
      erectile dysfunction 12 mo after RALP or RRP. DESIGN, SETTING, AND PARTICIPANTS:
      This was a prospective, controlled, nonrandomised trial of patients undergoing
      prostatectomy in 14 centres using RALP or RRP. Clinical-record forms and
      validated patient questionnaires at baseline and 12 mo after surgery were
      collected. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSES: Odds ratios (ORs) were
      calculated with logistic regression and adjusted for possible confounders. The
      primary end point was urinary incontinence (change of pad less than once in 24h
      vs one time or more per 24h) at 12 mo. Secondary end points were erectile
      dysfunction at 12 mo and positive surgical margins. RESULTS AND LIMITATIONS: At
      12 mo after RALP, 366 men (21.3%) were incontinent, as were 144 (20.2%) after
      RRP. The unadjusted OR was 1.08 (95% confidence interval [CI], 0.87-1.34).
      Erectile dysfunction was observed in 1200 men (70.4%) 12 mo after RALP and 531
      (74.7%) after RRP. The unadjusted OR was 0.81 (95% CI, 0.66-0.98). CONCLUSIONS:
      In a Swedish setting, RALP for prostate cancer was modestly beneficial in
      preserving erectile function compared with RRP, without a statistically
      significant difference regarding urinary incontinence or surgical margins.
      PATIENT SUMMARY: We compared patient-reported urinary incontinence after
      prostatectomy with two types of surgical technique. There was no statistically
      significant improvement in the rate of urinary leakage, but there was a small
      improvement regarding erectile function after robot-assisted operation.

PMID- 25770486
TI  - A Molecular Pathologic Framework for Risk Stratification of Stage T1 Urothelial
      Carcinoma.
AB  - BACKGROUND: One third of patients with stage T1 urothelial carcinoma (UC)
      progress to muscle-invasive disease requiring radical surgery. Thus, reliable
      tools are needed for risk stratification of stage T1 UC. OBJECTIVE: To
      investigate the extent to which stratification of stage T1 tumours into
      previously described molecular pathologic UC subtypes can provide improved
      information on tumour progression. DESIGN, SETTING, AND PARTICIPANTS: A
      population-based cohort of 167 primary stage T1 UCs was characterised by
      immunohistochemistry and classified into the molecular subtypes urobasal (Uro,
      32%), genomically unstable (GU, 58%), and squamous-cell-carcinoma-like (SCCL,
      10%). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Progression-free survival
      using univariate and multivariate models. RESULTS AND LIMITATIONS: Subtype
      classification was validated using nine additional markers with known subtype
      specific expression. Analysis of mRNA expression of progression biomarkers
      revealed a strong association with molecular subtype. Kaplan-Meier analyses
      showed that the risk of progression was low for Uro tumours and high for GU/SCCL
      tumours. High progression risk scores were found only for GU/SCCL tumours.
      Clinical risk factors such as multifocality, concomitant carcinoma in situ,
      invasion depth, lymphovascular invasion, and high CD3(+) lymphocyte infiltration
      were observed almost exclusively in GU/SCCL cases. CONCLUSIONS: Molecular
      subtypes Uro, GU, and SCCL were identified in an independent population-based
      cohort of stage T1 UCs. Biomarkers and clinical risk factors for progression were
      associated with molecular subtype. Rapidly progressing T1 tumours were of subtype
      GU or SCCL and had either a high progression risk score or an elevated CD3(+)
      cell count. PATIENT SUMMARY: We show that classification of stage T1 urothelial
      carcinoma into molecular subtypes can improve the identification of patients with
      progressing tumours.

PMID- 25770487
TI  - Re: Floris H. Groenendijk, Jeroen de Jong, Elisabeth E. Fransen van de Putte, et
      al. ERBB2 Mutations Characterize a Subgroup of Muscle-invasive Bladder Cancers
      with Excellent Response to Neoadjuvant Chemotherapy. Eur Urol. In press.
      http://dx.doi.org/10.1016/j.eururo.2015.01.014.

PMID- 25770488
TI  - Re: Christian Gratzke, Alexander Bachmann, Aurelien Descazeaud, et al. EAU
      Guidelines on the Assessment of Non-neurogenic Male Lower Urinary Tract Symptoms
      Including Benign Prostatic Obstruction. Eur Urol 2015;67:1099-109.

PMID- 25770489
TI  - Preface: special topic on supramolecular self-assembly at surfaces.
AB  - Supramolecular self-assembly at surfaces is one of the most exciting and active
      fields in Surface Science today. Applications can take advantage of two key
      properties: (i) versatile pattern formation over a broad length scale and (ii)
      tunability of electronic structure and transport properties, as well as frontier
      orbital alignment. It provides a new frontier for Chemical Physics as it uniquely
      combines the versatility of Organic Synthesis and the Physics of Interfaces. The
      Journal of Chemical Physics is pleased to publish this Special Topic Issue,
      showcasing recent advances and new directions. 

PMID- 25770490
TI  - Characterization of one-dimensional molecular chains of 4,4'-biphenyl
      diisocyanide on Au(111) by scanning tunneling microscopy.
AB  - The morphology and electronic structure of vapor deposited 4,4'
      biphenyldiisocyanide (BPDI) on a Au(111) surface were investigated using variable
      temperature scanning tunneling microscopy. When deposited at room temperature,
      BPDI molecules form one-dimensional molecular chains similar to that recently
      observed for the structurally related 1,4-phenyl diisocyanide (PDI). Compared to
      PDI, the longer periodicity for the BPDI molecular chains is consistent with the
      addition of a second phenyl ring and supports a structural model in which the
      BPDI molecules lie parallel to the surface and interconnected by Au-adatoms. The
      molecular chains are mostly aligned along the 110 direction of the Au(111)
      substrate, but exhibit frequent changes in angle that are consistent with
      directions between fcc and hcp three-fold hollow sites. Dispersion-corrected
      density functional theory calculations for one-dimensional chains of BPDI
      molecules bound end-to-end via their isocyanide groups to Au-adatoms reproduce
      the observed periodicity of the chains and show that this morphology is
      energetically favored over upright binding with one free -NC group. The spatially
      resolved conductance (dI/dV) map for BPDI on Au(111) exhibits a feature centered
      at -0.67 eV below the Fermi level which are delocalized along the chain with
      maxima at the Au-adatom and biphenyl positions. This occupied resonant feature is
      close to that previously observed for the PDI in both photoemission and
      conductance measurements and is attributed to an occupied interfacial state
      resulting from BPDI-Au interactions. 

PMID- 25770491
TI  - Self-assembled two-dimensional nanoporous molecular arrays and photoinduced
      polymerization of 4-bromo-4'-hydroxybiphenyl on Ag(111).
AB  - Self-assembled two-dimensional molecular arrays and photoinduced polymerization
      of 4-bromo-4'-hydroxybiphenyl on Ag(111) were studied using low-temperature
      scanning tunneling microscopy combined with density functional theory
      calculations. Square-like self-assembled structures of 4-bromo-4'-hydroxybiphenyl
      stabilized by intermolecular hydrogen and halogen bonds were transformed into
      hexagonal nanopores of biphenyl biradicals by 266 nm UV laser irradiation at 80
      K. The biradicals further coupled to each other and formed covalently linked
      polyphenylene polymer chains at room temperature. 

PMID- 25770492
TI  - Electrophilic surface sites as precondition for the chemisorption of pyrrole on
      GaAs(001) surfaces.
AB  - We report how the presence of electrophilic surface sites influences the
      adsorption mechanism of pyrrole on GaAs(001) surfaces. For this purpose, we have
      investigated the adsorption behavior of pyrrole on different GaAs(001)
      reconstructions with different stoichiometries and thus different surface
      chemistries. The interfaces were characterized by x-ray photoelectron
      spectroscopy, scanning tunneling microscopy, and by reflectance anisotropy
      spectroscopy in a spectral range between 1.5 and 5 eV. On the As-rich c(4 * 4)
      reconstruction that exhibits only nucleophilic surface sites, pyrrole was found
      to physisorb on the surface without any significant modification of the
      structural and electronic properties of the surface. On the Ga-rich GaAs(001)-(4
      * 2)/(6 * 6) reconstructions which exhibit nucleophilic as well as electrophilic
      surface sites, pyrrole was found to form stable covalent bonds mainly to the
      electrophilic (charge deficient) Ga atoms of the surface. These results clearly
      demonstrate that the existence of electrophilic surface sites is a crucial
      precondition for the chemisorption of pyrrole on GaAs(001) surfaces. 

PMID- 25770493
TI  - Adsorption of PTCDA on Si(001) - 2 * 1 surface.
AB  - Adsorption structures of the 3,4,9,10-perylenetetracarboxylic dianhydride (PTCDA)
      molecule on the clean Si(001) - 2 * 1 surface were investigated using scanning
      tunneling microscopy (STM) experiments in conjunction with first principles
      theoretical calculations. Four dominant adsorption structures were observed in
      the STM experiments and their atomic coordinates on the Si(001) surface were
      determined by comparison between the experimental STM images and the theoretical
      simulations. Maximizing the number of the Si-O bonds is more crucial than that of
      the Si-C bonds in the PTCDA adsorption. 

PMID- 25770494
TI  - Molecular engineering of Schiff-base linked covalent polymers with diverse
      topologies by gas-solid interface reaction.
AB  - The design and construction of molecular nanostructures with tunable topological
      structures are great challenges in molecular nanotechnology. Herein, we
      demonstrate the molecular engineering of Schiff-base bond connected molecular
      nanostructures. Building module construction has been adopted to modulate the
      symmetry of resulted one dimensional (1D) and two dimensional (2D) polymers.
      Specifically, we have designed and constructed 1D linear and zigzag polymers, 2D
      hexagonal and chessboard molecular nanostructures by varying the number of
      reactive sites and geometry and symmetry of precursors. It is demonstrated that
      high-quality conjugated polymers can be fabricated by using gas-solid interface
      reaction. The on-demanding synthesis of polymeric architectures with diverse
      topologies paves the way to fabricate molecular miniature devices with various
      desired functionalities. 

PMID- 25770495
TI  - Tribromobenzene on Cu(111): Temperature-dependent formation of halogen-bonded,
      organometallic, and covalent nanostructures.
AB  - The temperature-controlled surface-assisted synthesis of halogen bonded,
      organometallic, and covalent nanostructures based on 1,3,5-tribromo-benzene
      (TriBB) was studied with scanning tunneling microscopy and X-ray photoemission
      spectroscopy in ultrahigh vacuum. Vapor deposition of TriBB onto a Cu(111)
      surface held at 90 K leads to the formation of large domains of a honeycomb-like
      organic monolayer structure stabilized by triangular nodes with Br?Br
      intermolecular bonds. Upon annealing the organic monolayer to ~140 K, a new
      hexagonal close-packed structure with intact TriBB molecules connected by Cu
      adatoms is formed. Further warming up the sample to 300 K gives rise to the
      scission of C-Br bonds and formation of C-Cu-C bonds between phenyl fragments
      such that stable dendritic organometallic networks are formed. Larger islands of
      organometallic networks are obtained by maintaining the temperature of Cu(111) at
      420 K during deposition of TriBB. Simultaneously, large islands of Br atoms are
      formed around the organometallic networks. Annealing the more extended
      organometallic network (prepared at 420 K) to 520 K leads to the formation of a
      branched covalent organic framework (COF) which comprises structural elements of
      porous graphene and is surrounded by Br islands. These organometallic networks
      and COFs appear as small dendritic and branched domains, most likely due to the
      steric influence exerted by the Br islands. 

PMID- 25770496
TI  - Chemical insight from density functional modeling of molecular adsorption:
      Tracking the bonding and diffusion of anthracene derivatives on Cu(111) with
      molecular orbitals.
AB  - We present a method of analyzing the results of density functional modeling of
      molecular adsorption in terms of an analogue of molecular orbitals. This approach
      permits intuitive chemical insight into the adsorption process. Applied to a set
      of anthracene derivates (anthracene, 9,10-anthraquinone, 9,10-dithioanthracene,
      and 9,10-diselenonanthracene), we follow the electronic states of the molecules
      that are involved in the bonding process and correlate them to both the molecular
      adsorption geometry and the species' diffusive behavior. We additionally provide
      computational code to easily repeat this analysis on any system. 

PMID- 25770497
TI  - Heterogeneous patterns on block copolymer thin film via solvent annealing: Effect
      on protein adsorption.
AB  - Heterogeneous patterns consisting of nanometer-scaled hydrophobic/hydrophilic
      domains were generated by self-assembly of poly(styrene)-block-poly(2
      hydroxyethyl methacrylate) (PS-b-PHEMA) block copolymer thin film. The effect of
      the heterogeneity of the polymer film surface on the nonspecific adsorption of
      the protein human plasma fibrinogen (FBN, 5.0 * 5.0 * 47.5 nm(3)) was
      investigated. The kinetics of the FBN adsorption varies from a single-component
      Langmuir model on homogeneous hydrophilic PHEMA to a two-stage spreading
      relaxation model on homogeneous hydrophobic PS surface. On a heterogeneous PS-b
      PHEMA surface with majority PS part, the initial FBN adsorption rate remains the
      same as that on the homogeneous PS surface. However, hydrophilic PHEMA
      microdomains on the heterogeneous surface slow down the second spreading stage of
      the FBN adsorption process, leading to a surface excess of adsorbed FBN molecules
      less than the presumed one simply calculated as adsorption onto multiple domains.
      Importantly, when the PS-b-PHEMA surface is annealed to form minority domelike PS
      domains (diameter: ~50-100 nm) surrounded by a majority PHEMA matrix, such
      surface morphology proves to be strongly protein-repulsive. These interesting
      findings can be attributed to the enhancement of the spread FBN molecule in a
      mobile state by the heterogeneity of polymer film surface before irreversible
      adsorption occurs. 

PMID- 25770498
TI  - Thermodynamic versus kinetic control in self-assembly of zero-, one-, quasi-two-,
      and two-dimensional metal-organic coordination structures.
AB  - Four types of metal-organic structures exhibiting specific dimensionality were
      studied using scanning tunneling microscopy and Monte Carlo simulations. The four
      structures were self-assembled out of specifically designed molecular building
      blocks via the same coordination motif on an Au(111) surface. We found that the
      four structures behaved differently in response to thermal annealing treatments:
      The two-dimensional structure was under thermodynamic control while the
      structures of lower dimension were under kinetic control. Monte Carlo simulations
      revealed that the self-assembly pathways of the four structures are associated
      with the characteristic features of their specific heat. These findings provide
      insights into how the dimensionality of supramolecular coordination structures
      affects their thermodynamic properties. 

PMID- 25770499
TI  - C60 chain phases on ZnPc/Ag(111) surfaces: Supramolecular organization driven by
      competing interactions.
AB  - Serpentine chain C60 phases were observed in scanning tunneling microscopy (STM)
      images of C60 layers on zinc phthalocyanine (ZnPc) or pentacene covered Ag(111)
      and Au(111) surfaces. This low-density, quasi-one-dimensional organization
      contrasts starkly with the close-packed hexagonal phases observed for C60 layers
      on bare metal substrates. STM was employed to perform a detailed investigation of
      these chain structures for C60/ZnPc/Ag(111) heterolayers. Motivated by the
      similarity of these chain phases, and the chain and stripe organization occurring
      in dipole-fluid systems, we investigated a model based on competing van der Waals
      attractions and electrostatic repulsions between C60 molecules as an explanation
      for the driving force behind these monolayer phases. Density functional theory
      (DFT) calculations revealed significant charge transfer to C60 from the Ag(111)
      substrate, through the intervening ZnPc layer, inducing electrostatic
      interactions between C60 molecules. Molecular dynamics simulations performed with
      attractive van der Waals interactions plus repulsive dipole-dipole interactions
      reproduced the C60 chain phases with dipole magnitudes consistent with DFT
      calculations. 

PMID- 25770500
TI  - Construction of single-crystalline supramolecular networks of perchlorinated hexa
      peri-hexabenzocoronene on Au(111).
AB  - The self-assembly of the perchlorinated hexa-peri-hexabenzocoronene (PCHBC)
      molecules on Au(111) has been studied by a low temperature scanning tunneling
      microscopy (STM) combining with density functional theory based first principle
      calculations. Highly ordered supramolecular networks with single domains limited
      by the terraces are formed on Au(111) substrate. High resolution images of the
      PCHBC molecules, confirmed by first principle simulations, are obtained. It
      reveals the close-packed arrangement of the PCHBC molecules on Au(111). The
      calculated charge distribution of PCHBC molecules shows the existence of
      attractive halogen-halogen interaction between neighboring molecules. Compared
      with the disordered adsorption of hexa-peri-hexabenzocoronene on Au(111), we
      conclude that the formation of attractive Cl???Cl interactions between neighbors
      is the key factor to form the highly ordered, close-packed networks. Due to the
      steric hindrance resulted from the peripheral chlorine atoms, the PCHBC molecule
      is contorted and forms the doubly concave conformation, which is different from
      the hexa-peri-hexabenzocoronene with a planar structure. By using this
      supramolecular network as a template, we deposited C60 molecules on it at room
      temperature with low coverage. The STM images taken at low temperature show that
      the C60 molecules are mono-dispersed on the networks and adsorb on top of the
      PCHBC molecules, forming a typical concave-convex host-guest system.

PMID- 25770501
TI  - Self-assembly of diblock copolymer confined in an array-structure space.
AB  - The combination of top-down and bottom-up technologies is an effective method to
      create the novel nanostructures with long range order in the field of advanced
      materials manufacture. In this work, we employed a polymeric self-consistent
      field theory to investigate the pattern formation of diblock copolymer in a 2D
      confinement system designed by filling pillar arrays with various 2D shapes such
      as squares, rectangles, and triangles. Our simulation shows that in such
      confinement system, the microphase structure of diblock copolymer strongly
      depends on the pitch, shape, size, and rotation of the pillar as well as the
      surface field of confinement. The array structures can not only induce the
      formation of new phase patterns but also control the location and orientation of
      pattern structures. Finally, several methods to tune the commensuration and
      frustration of array-structure confinement are proposed and examined. 

PMID- 25770502
TI  - Redox-active on-surface polymerization of single-site divalent cations from pure
      metals by a ketone-functionalized phenanthroline.
AB  - Metallic iron, chromium, or platinum mixing with a ketone-functionalized
      phenanthroline ligand on a single crystal gold surface demonstrates redox
      activity to a well-defined oxidation state and assembly into thermally stable,
      one dimensional, polymeric chains. The diverging ligand geometry incorporates
      redox-active sub-units and bi-dentate binding sites. The gold surface provides a
      stable adsorption environment and directs growth of the polymeric chains, but is
      inert with regard to the redox chemistry. These systems are characterized by
      scanning tunnelling microscopy, non-contact atomic force microscopy, and X-ray
      photoelectron spectroscopy under ultra-high vacuum conditions. The relative
      propensity of the metals to interact with the ketone group is examined, and it is
      found that Fe and Cr more readily complex the ligand than Pt. The formation and
      stabilization of well-defined transition metal single-sites at surfaces may open
      new routes to achieve higher selectivity in heterogeneous catalysts. 

PMID- 25770504
TI  - Impact of branching on the supramolecular assembly of thioethers on Au(111).
AB  - Alkanethiolate monolayers are one of the most comprehensively studied self
      assembled systems due to their ease of preparation, their ability to be
      functionalized, and the opportunity to control their thickness perpendicular to
      the surface. However, these systems suffer from degradation due to oxidation and
      defects caused by surface etching and adsorbate rotational boundaries. Thioethers
      offer a potential alternative to thiols that overcome some of these issues and
      allow dimensional control of self-assembly parallel to the surface. Thioethers
      have found uses in surface modification of nanoparticles, and chiral thioethers
      tethered to catalytically active surfaces have been shown to enable
      enantioselective hydrogenation. However, the effect of structural, chemical, and
      chiral modifications of the alkyl chains of thioethers on their self-assembly has
      remained largely unstudied. To elucidate how molecular structure, particularly
      alkyl branching and chirality, affects molecular self-assembly, we compare four
      related thioethers, including two pairs of structural isomers. The self-assembly
      of structural isomers N-butyl methyl sulfide and tert-butyl methyl sulfide was
      studied with high resolution scanning tunneling microscopy (STM); our results
      indicate that both molecules form highly ordered arrays despite the bulky tert
      butyl group. We also investigated the effect of intrinsic chirality in the alkyl
      tails on the adsorption and self-assembly of butyl sec-butyl sulfide (BSBS) with
      STM and density functional theory and contrast our results to its structural
      isomer, dibutyl sulfide. Calculations provide the relative stability of the four
      stereoisomers of BSBS and STM imaging reveals two prominent monomer forms.
      Interestingly, the racemic mixture of BSBS is the only thioether we have examined
      to date that does not form highly ordered arrays; we postulate that this is due
      to weak enantiospecific intermolecular interactions that lead to the formation of
      energetically similar but structurally different assemblies. Furthermore, we
      studied all of the molecules in their monomeric molecular rotor form, and the
      surface-adsorbed chirality of the three asymmetric thioethers is distinguishable
      in STM images. 

PMID- 25770505
TI  - 1D self-assembly of chemisorbed thymine on Cu(110) driven by dispersion forces.
AB  - Adsorption of thymine on a defined Cu(110) surface was studied using reflection
      absorption infrared spectroscopy (RAIRS), temperature programmed desorption
      (TPD), and scanning tunnelling microscopy (STM). In addition, density functional
      theory (DFT) calculations were undertaken in order to further understand the
      energetics of adsorption and self-assembly. The combination of RAIRS, TPD, and
      DFT results indicates that an upright, three-point-bonded adsorption
      configuration is adopted by the deprotonated thymine at room temperature. DFT
      calculations show that the upright configuration adopted by individual molecules
      arises as a direct result of strong O-Cu and N-Cu bonds between the molecule and
      the surface. STM data reveal that this upright thymine motif self-assembles into
      1D chains, which are surprisingly oriented along the open-packed [001] direction
      of the metal surface and orthogonal to the alignment of the functional groups
      that are normally implicated in H-bonding interactions. DFT modelling of this
      system reveals that the molecular organisation is actually driven by dispersion
      interactions, which cause a slight tilt of the molecule and provide the major
      driving force for assembly into dimers and 1D chains. The relative orientations
      and distances of neighbouring molecules are amenable for pi-pi stacking,
      suggesting that this is an important contributor in the self-assembly process. 

PMID- 25770503
TI  - Living on the edge: Tuning supramolecular interactions to design two-dimensional
      organic crystals near the boundary of two stable structural phases.
AB  - One of the benefits of supramolecular assemblies that form at dynamic interfaces
      is the opportunity to develop condensed phase systems that respond to
      environmental stimuli. A prerequisite of this responsive behavior is that the
      supramolecular system be designed to sit very near the stability of two or more
      crystal structures. We have created such a bi-phasic system with aryl-triazole
      oligomers by investigating how phase morphology is controlled by the interplay
      between interactions that involve the oligomer's dipolar cores (DeltaMU = 3.5
      debye), van der Waals contacts of their pendant alkyl chains (C4-C18), and close
      contact hydrogen bonding. Scanning tunneling microscopy experiments conducted at
      the solution-graphite interface allow sub-molecular resolution of the ordered
      monolayers to unambiguously determine the packing and structure of two principle
      phases, alpha and beta. The system is balanced very near the edge of phase
      stability, evidenced by co-existent phases present over short time frames and by
      the changes in preference between the two 2D supramolecular assemblies that occur
      with small modifications to the molecular structure. We demonstrate that the bi
      phasic behavior can be understood as a balance between electrostatic interactions
      and van der Waals contacts, two variables within a larger parameter space,
      allowing synthetic design to move this solution-surface system across the
      stability boundary of different condensed-phase structures. These findings are a
      foundation for the development of environmentally responsive 2D supramolecular
      arrays. 

PMID- 25770506
TI  - Redox-activity and self-organization of iron-porphyrin monolayers at a
      copper/electrolyte interface.
AB  - The electrochemical behaviour and molecular structure of a layer of water-soluble
      5,10,15,20-Tetrakis-(N-methyl-4-pyridyl)-porphyrin-Fe(III) pentatosylate,
      abbreviated as FeTMPyP, on a chloride modified Cu(100) electrode surface were
      investigated by means of cyclic voltammetry (CV) and in-situ electrochemical
      scanning tunneling microscopy. Voltammetric results of HOPG in an electrolyte
      containing FeTMPyP molecules indicate three distinguishable redox steps involving
      both the central iron metal and the pi-conjugated ring system. However, only the
      first two reduction steps are observable within the narrow potential window of
      CVs of Cu(100) measured in the same electrolyte. In the potential range below the
      first reduction peak, at which the [Fe(III)TMPyP](5+) molecules are reduced to
      the corresponding [Fe(II)TMPyP](4+) species, in-situ scanning tunneling
      microscopy (STM) images revealed, for the first time, a highly ordered adlayer of
      this reduced porphyrin species on the chloride terminated Cu(100) surface. The
      ordered adlayer exhibits a (quasi)square unit cell with the lattice vectors |a
      >2|=|b->2|=1.53+/-0.1 nm and an angle of 93 degrees  +/- 2 degrees  between them.
      A model is proposed based on the STM observation illustrating the arrangement of
      the [Fe(II)TMPyP](4+) molecules at the electrolyte/copper interface.

PMID- 25770507
TI  - Electronic structure at transition metal phthalocyanine-transition metal oxide
      interfaces: Cobalt phthalocyanine on epitaxial MnO films.
AB  - The electronic structure of the interface between cobalt phthalocyanine (CoPc)
      and epitaxially grown manganese oxide (MnO) thin films is studied by means of
      photoemission (PES) and X-ray absorption spectroscopy (XAS). Our results reveal a
      flat-lying adsorption geometry of the molecules on the oxide surface which allows
      a maximal interaction between the pi-system and the substrate. A charge transfer
      from MnO, in particular, to the central metal atom of CoPc is observed by both
      PES and XAS. The change of the shape of N-K XAS spectra at the interface points,
      however, to the involvement of the Pc macrocycle in the charge transfer process.
      As a consequence of the charge transfer, energetic shifts of MnO related core
      levels were observed, which are discussed in terms of a Fermi level shift in the
      semiconducting MnO films due to interface charge redistribution. 

PMID- 25770508
TI  - Amino-terminated biphenylthiol self-assembled monolayers as highly reactive
      molecular templates.
AB  - Self-assembled monolayers (SAMs) with amino tail groups are of interest due to
      their ability of coupling further compounds. Such groups can be, in particular,
      created by electron irradiation of nitro- or nitrile-substituted aromatic SAMs,
      which provide a basis for chemical nanolithography and the fabrication of
      functionalized nanomembranes. An estimate of reactivity of the created amino
      groups requires a reference system of homogeneous, amino-terminated aromatic
      SAMs, which can also be used as a highly reactive molecular template. Here, we
      describe the synthesis of 4'-aminobiphenyl-4-thiol (ABPT) and SAMs prepared from
      this precursor on Au(111). The monolayers were characterized by X-ray
      photoelectron spectroscopy and near edge X-ray absorption fine structure
      spectroscopy, which revealed that they are well defined, chemically uniform,
      densely packed, and highly ordered. To examine the influence of electron
      irradiation on the reactivity of the terminal amino groups, ABPT SAMs were
      exposed to low energy (50 eV) electrons up to a dose of 40 mC/cm(2) and,
      subsequently, immersed in either trifluoroacetic, pentafluoropropionic, or
      heptafluorobutyric anhydride. Analysing the amount of the attached anhydride
      species made it possible to determine the percentage of reactive amino groups as
      well as the effect of steric hindrance upon the coupling reaction. The above
      results are compared with those obtained for the well-established nitro
      substituted biphenylthiol monolayers. 

PMID- 25770509
TI  - Influence of water on supra-molecular assembly of 4, 4'-dihydroxy azobenzene on
      Ag(111).
AB  - We explore co-deposition of water and 4, 4'-dihydroxy azobenzene on Ag(111) by
      low-temperature scanning tunneling microscopy at different water-to-azobenzene
      ratios. At all ratios, the water interacts with the hydroxyl end groups of the
      molecule replacing the direct hydrogen bonding. The change in bonding reduces the
      azobenzene density as compared to the one in the closed-packed waterless
      azobenzene structure. At intermediate water-to-azobenzene ratios, pores are
      formed in the azobenzene layer at nanometer distance from the water. At high
      water-to-azobenzene ratios, a water superstructure with a 1.4 nm * 1.4 nm unit
      cell develops. Our results point to a method to vary the density of an organic
      layer by tuning the amount of an inorganic additive. 

PMID- 25770510
TI  - Self-assembly of strongly dipolar molecules on metal surfaces.
AB  - The role of dipole-dipole interactions in the self-assembly of dipolar organic
      molecules on surfaces is investigated. As a model system, strongly dipolar model
      molecules, p-benzoquinonemonoimine zwitterions (ZI) of type C6H2(? NHR)2(? O)2 on
      crystalline coinage metal surfaces were investigated with scanning tunneling
      microscopy and first principles calculations. Depending on the substrate, the
      molecules assemble into small clusters, nano gratings, and stripes, as well as in
      two-dimensional islands. The alignment of the molecular dipoles in those
      assemblies only rarely assumes the lowest electrostatic energy configuration.
      Based on calculations of the electrostatic energy for various experimentally
      observed molecular arrangements and under consideration of computed dipole
      moments of adsorbed molecules, the electrostatic energy minimization is ruled out
      as the driving force in the self-assembly. The structures observed are mainly the
      result of a competition between chemical interactions and substrate effects. The
      substrate's role in the self-assembly is to (i) reduce and realign the molecular
      dipole through charge donation and back donation involving both the molecular
      HOMO and LUMO, (ii) dictate the epitaxial orientation of the adsorbates,
      specifically so on Cu(111), and (iii) inhibit attractive forces between
      neighboring chains in the system ZI/Cu(111), which results in regularly spaced
      molecular gratings. 

PMID- 25770511
TI  - Selection of conformational states in self-assembled surface structures formed
      from an oligo(naphthylene-ethynylene) 3-bit binary switch.
AB  - Supra-molecular self-assembly on surfaces often involves molecular conformational
      flexibility which may act to enrich the variation and complexity of the
      structures formed. However, systematic and explicit investigations of how
      molecular conformational states are selected in surface self-assembly processes
      are relatively scarce. Here, we use a combination of high-resolution scanning
      tunneling microscopy and Density Functional Theory (DFT) calculations to
      investigate self-assembly for a custom-designed molecule capable of assuming
      eight distinct surface conformations (four enantiomeric pairs). The conformations
      result from binary positions of n = 3 naphtalene units on a linear
      oligo(naphthylene-ethynylene) backbone. On Au(111), inter-molecular interactions
      involving carboxyl and bulky tert-butyl-phenyl functional groups induce the
      molecules to form two ordered phases with brick-wall and lamella structure,
      respectively. These structures each involve molecules in two conformational
      states, and there is a clear separation between the conformers involved in the
      two types of structures. On Cu(111), individual molecules isolated by carboxylate
      substrate binding show a distribution involving all possible conformational
      states. Together these observations imply selection and adaptation of
      conformational states upon molecular self-assembly. From DFT modeling and
      statistical analysis of the molecular conformations, the observed selection of
      conformational states is attributed to steric interaction between the naphthalene
      units. The present study enhances our understanding of how ordering and selection
      of molecular conformations is controlled by intermolecular interactions in a
      complex situation with many distinct conformational states for the participating
      molecules. 

PMID- 25770512
TI  - Self-assembly of indole-2-carboxylic acid at graphite and gold surfaces.
AB  - Model systems are critical to our understanding of self-assembly processes. As
      such, we have studied the surface self-assembly of a small and simple molecule,
      indole-2-carboxylic acid (I2CA). We combine density functional theory gas-phase
      (DFT) calculations with scanning tunneling microscopy to reveal details of I2CA
      assembly in two different solvents at the solution/solid interface, and on
      Au(111) in ultrahigh vacuum (UHV). In UHV and at the trichlorobenzene/highly
      oriented pyrolytic graphite (HOPG) interface, I2CA forms epitaxial lamellar
      structures based on cyclic OH?O carboxylic dimers. The structure formed at the
      heptanoic acid/HOPG interface is different and can be interpreted in a model
      where heptanoic acid molecules co-adsorb on the substrate with the I2CA, forming
      a bicomponent commensurate unit cell. DFT calculations of dimer energetics
      elucidate the basic building blocks of these structures, whereas calculations of
      periodic two-dimensional assemblies reveal the epitaxial effects introduced by
      the different substrates. 

PMID- 25770513
TI  - Benzene derivatives adsorbed to the Ag(111) surface: Binding sites and electronic
      structure.
AB  - Dispersion corrected Density Functional Theory calculations were employed to
      study the adsorption of benzenes derivatized with functional groups encompassing
      a large region of the activated/deactivated spectrum to the Ag(111) surface.
      Benzenes substituted with weak activating or deactivating groups, such as methyl
      and fluoro, do not have a strong preference for adsorbing to a particular site on
      the substrate, with the corrugations in the potential energy surface being
      similar to those of benzene. Strong activating (N(CH3)2) and deactivating (NO2)
      groups, on the other hand, possess a distinct site preference. The nitrogen in
      the former prefers to lie above a silver atom (top site), but in the latter a
      hollow hexagonal-closed-packed (Hhcp) site of the Ag(111) surface is favored
      instead. Benzenes derivatized with classic activating groups donate electron
      density from their highest occupied molecular orbital to the surface, and those
      functionalized with deactivating groups withdraw electron density from the
      surface into orbitals that are unoccupied in the gas phase. For benzenes
      functionalized with two substituents, the groups that are strongly activating or
      deactivating control the site preference and the other groups assume sites that
      are, to a large degree, dictated by their positions on the benzene ring. The
      relative stabilities of the ortho, meta, and para positional isomers of
      disubstituted benzenes can, in some cases, be modified by adsorption to the
      surface. 

PMID- 25770514
TI  - Supramolecular order and structural dynamics: A STM study of 2H
      tetraphenylporphycene on Cu(111).
AB  - The adsorption of 2H-tetraphenylporphycene (2HTPPc) on Cu(111) was investigated
      by scanning tunneling microscopy (STM). At medium coverages, supramolecular
      ordered islands are observed. The individual 2HTPPc molecules appear as two pairs
      of intense protrusions which are separated by an elongated depression. In the
      islands, the molecules are organized in rows oriented along one of the close
      packed Cu(111) substrate rows; the structure is stabilized by T-type interactions
      of the phenyl substituents of neighboring molecules. Two types of rows are
      observed, namely, highly ordered rows in which all molecules exhibit the same
      orientation, and less ordered rows in which the molecules exhibit two
      perpendicular orientations. Altogether, three different azimuthal orientations of
      2HTPPc are observed within one domain, all of them rotated by 15 degrees  +/- 1
      degrees  relative to one closed packed Cu direction. The highly ordered rows are
      always separated by either one or two less ordered rows, with the latter
      structure being the thermodynamically more stable one. The situation in the
      islands is highly dynamic, such that molecules in the less ordered rows
      occasionally change orientation, also complete highly ordered rows can move. The
      supramolecular order and structural dynamics are discussed on the basis of the
      specific molecule-substrate and molecule-molecule interactions. 

PMID- 25770515
TI  - From hydrogen bonding to metal coordination and back: Porphyrin-based networks on
      Ag(111).
AB  - The self-assembly of a metal-free porphyrin bearing two pyridyl coordinating
      sites and two pentyl chains at trans meso positions was investigated under
      ultrahigh vacuum on a Ag(111) surface by scanning tunneling microscopy (STM). The
      STM measurements revealed a well-ordered close-packed structure with a rhombic
      unit cell for coverages <=1 monolayer with their molecular plane parallel to the
      surface. The growth direction of the molecular islands is aligned along the step
      edges, which are restructured due to molecule-substrate interactions. The shorter
      unit cell vector of the molecular superstructure follows the<1-10>direction of
      the Ag(111) substrate. Hydrogen bonds between pyridyl and pyrrole groups of
      neighboring molecules as well as weak van der Waals forces between the pentyl
      chains stabilize the superstructure. Deposition of cobalt atoms onto the close
      packed structure at room temperature leads to the formation of a hexagonal porous
      network stabilized by metal-ligand bonding between the pyridyl ligands and the
      cobalt atoms. Thermal annealing of the Co-coordination network at temperatures
      >450 K results in the transformation of the hexagonal network into a second close
      packed structure. Changes in the molecule-substrate interactions due to
      metalation of the porphyrin core with Co as well as intermolecular interactions
      can explain the observed structural transformations.

PMID- 25770516
TI  - Hydrogen-bonded clusters of 1, 1'-ferrocenedicarboxylic acid on Au(111) are
      initially formed in solution.
AB  - Low-temperature scanning tunneling microscopy is used to observe self-assembled
      structures of ferrocenedicarboxylic acid (Fc(COOH)2) on the Au(111) surface. The
      surface is prepared by pulse-deposition of Fc(COOH)2 dissolved in methanol, and
      the solvent is evaporated before imaging. While the rows of hydrogen-bonded
      dimers that are common for carboxylic acid species are observed, the majority of
      adsorbed Fc(COOH)2 is instead found in six-molecule clusters with a well-defined
      and chiral geometry. The coverage and distribution of these clusters are
      consistent with a random sequential adsorption model, showing that solution-phase
      species are determinative of adsorbate distribution for this system under these
      reaction conditions. 

PMID- 25770517
TI  - Temperature-dependent self-assembly of NC-Ph5-CN molecules on Cu(111).
AB  - We present the results of temperature-dependent self-assembly of dicarbonitrile
      pentaphenyl molecules (NC-Ph5-CN) on Cu(111). Our low-temperature scanning
      tunneling microscopy study reveals the formation of metal-organic and purely
      organic structures, depending on the substrate temperature during deposition (160
      300 K), which determines the availability of Cu adatoms at the surface. We use
      tip functionalization with CO to obtain submolecular resolution and image the
      coordination atoms, enabling unequivocal identification of metal-coordinated
      nodes and purely organic ones. Moreover, we discuss the somewhat surprising
      structure obtained for deposition and measurement at 300 K. 

PMID- 25770518
TI  - True perylene epitaxy on Ag(110) driven by site recognition effect.
AB  - We present a STM study of room temperature perylene adsorption on the Ag(110)
      surface. We have found a 2D perylene crystalline phase coexisting with the
      perylene liquid phase under thermal equilibrium. The reversible precipitation of
      the liquid phase at sub-monolayer coverage reveals the well ordered chiral
      crystalline phase existing in two enantiomorphic configurations of the ((-2)(3)
      (5)(2)) and ((2)(3) (5)(-2)) symmetry. This chiral phase is spatially separated
      into the 2D enantiopure islands of tens of nanometers size randomly distributed
      on the substrate and surrounded by the liquid medium. Analysis of surface
      registry of the crystalline phase combined with modeling of the intermolecular
      interactions indicates that its structure and symmetry is determined by a
      specific balance between the intermolecular attraction and intrinsic ability of
      the perylene aromatic board to recognize adsorption sites. The recognition effect
      was found to be strong enough to pin half of the perylene molecules into defined
      adsorption sites providing the structure skeleton. The attractive intermolecular
      interaction was found to be strong enough to bind another half of the molecules
      to the perylene skeleton shaping the true epitaxial structure.

PMID- 25770519
TI  - Temperature-controlled metal/ligand stoichiometric ratio in Ag-TCNE coordination
      networks.
AB  - The deposition of tetracyanoethylene (TCNE) on Ag(111), both at Room Temperature
      (RT, 300 K) and low temperatures (150 K), leads to the formation of coordination
      networks involving silver adatoms, as revealed by Variable-Temperature Scanning
      Tunneling Microscopy. Our results indicate that TCNE molecules etch away material
      from the step edges and possibly also from the terraces, which facilitates the
      formation of the observed coordination networks. Moreover, such process is
      temperature dependent, which allows for different stoichiometric ratios between
      Ag and TCNE just by adjusting the deposition temperature. X-ray Photoelectron
      Spectroscopy and Density Functional Theory calculations reveal that charge
      transfer from the surface to the molecule and the concomitant geometrical
      distortions at both sides of the organic/inorganic interface might facilitate the
      extraction of silver atoms from the step-edges and, thus, its incorporation into
      the observed TCNE coordination networks. 

PMID- 25770520
TI  - Quantum confinement in self-assembled two-dimensional nanoporous honeycomb
      networks at close-packed metal surfaces.
AB  - Quantum confinement of a two-dimensional electron gas by supramolecular
      nanoporous networks is investigated using the boundary elements method based on
      Green's functions for finite geometries and electron plane wave expansion for
      periodic systems. The "particle in a box" picture was analyzed for cases with
      selected symmetries that model previously reported architectures constructed from
      organic and metal-organic scattering centers confining surface state electrons of
      Ag(111) and Cu(111). First, by analyzing a series of cases with systematically
      defined parameters (scattering geometry, potentials, and effective broadening),
      we demonstrate how the scattering processes affect the properties of the confined
      electrons. For the features of the local density of states reported by scanning
      tunneling spectroscopy (STS), we disentangle the contributions of lifetime
      broadening and splitting of quantum well states due to coupling of neighboring
      quantum dots. For each system, we analyze the local electron density distribution
      and relate it to the corresponding band structure as calculated within the plane
      wave expansion framework. Then, we address two experimental investigations, where
      in one case only STS data and in the other case mainly angle-resolved
      photoemission spectroscopy (ARPES) data were reported. In both cases, the
      experimental findings can be successfully simulated. Furthermore, the missing
      information can be complemented because our approach allows to correlate the
      information obtained by STS with that of ARPES. The combined analysis of several
      observations suggests that the scattering potentials created by the network
      originate primarily from the adsorbate-induced changes of the local surface
      dipole barrier. 

PMID- 25770521
TI  - On the stability of surface-confined nanoporous molecular networks.
AB  - Self-assembly of molecular building blocks into two-dimensional nanoporous
      networks has been a topic of broad interest for many years. However, various
      factors govern the specific outcome of the self-assembly process, and
      understanding and controlling these are key to successful creation. In this work,
      the self-assembly of two alkylated dehydrobenzo[12]annulene building blocks was
      compared at the liquid-solid interface. It turned out that only a small chemical
      modification within the building blocks resulted in enhanced domain sizes and
      stability of the porous packing relative to the dense linear packing. Applying a
      thermodynamic model for phase transition revealed some key aspects for network
      formation. 

PMID- 25770522
TI  - Minimising biases in full configuration interaction quantum Monte Carlo.
AB  - We show that Full Configuration Interaction Quantum Monte Carlo (FCIQMC) is a
      Markov chain in its present form. We construct the Markov matrix of FCIQMC for a
      two determinant system and hence compute the stationary distribution. These
      solutions are used to quantify the dependence of the population dynamics on the
      parameters defining the Markov chain. Despite the simplicity of a system with
      only two determinants, it still reveals a population control bias inherent to the
      FCIQMC algorithm. We investigate the effect of simulation parameters on the
      population control bias for the neon atom and suggest simulation setups to, in
      general, minimise the bias. We show a reweight ing scheme to remove the bias
      caused by population control commonly used in diffusion Monte Carlo [Umrigar et
      al., J. Chem. Phys. 99, 2865 (1993)] is effective and recommend its use as a post
      processing step. 

PMID- 25770523
TI  - Surface hopping outperforms secular Redfield theory when reorganization energies
      range from small to moderate (and nuclei are classical).
AB  - We evaluate the accuracy of Tully's surface hopping algorithm for the spin-boson
      model in the limit of small to moderate reorganization energy. We calculate
      transition rates between diabatic surfaces in the exciton basis and compare
      against exact results from the hierarchical equations of motion; we also compare
      against approximate rates from the secular Redfield equation and Ehrenfest
      dynamics. We show that decoherence-corrected surface hopping performs very well
      in this regime, agreeing with secular Redfield theory for very weak system-bath
      coupling and outperforming secular Redfield theory for moderate system-bath
      coupling. Surface hopping can also be extended beyond the Markovian limits of
      standard Redfield theory. Given previous work [B. R. Landry and J. E. Subotnik,
      J. Chem. Phys. 137, 22A513 (2012)] that establishes the accuracy of decoherence
      corrected surface-hopping in the Marcus regime, this work suggests that surface
      hopping may well have a very wide range of applicability. 

PMID- 25770524
TI  - Parallel scalability of Hartree-Fock calculations.
AB  - Quantum chemistry is increasingly performed using large cluster computers
      consisting of multiple interconnected nodes. For a fixed molecular problem, the
      efficiency of a calculation usually decreases as more nodes are used, due to the
      cost of communication between the nodes. This paper empirically investigates the
      parallel scalability of Hartree-Fock calculations. The construction of the Fock
      matrix and the density matrix calculation are analyzed separately. For the
      former, we use a parallelization of Fock matrix construction based on a static
      partitioning of work followed by a work stealing phase. For the latter, we use
      density matrix purification from the linear scaling methods literature, but
      without using sparsity. When using large numbers of nodes for moderately sized
      problems, density matrix computations are network-bandwidth bound, making
      purification methods potentially faster than eigendecomposition methods. 

PMID- 25770525
TI  - Anomalous law of cooling.
AB  - We analyze the temperature relaxation phenomena of systems in contact with a
      thermal reservoir that undergoes a non-Markovian diffusion process. From a
      generalized Langevin equation, we show that the temperature is governed by a law
      of cooling of the Newton's law type in which the relaxation time depends on the
      velocity autocorrelation and is then characterized by the memory function. The
      analysis of the temperature decay reveals the existence of an anomalous cooling
      in which the temperature may oscillate. Despite this anomalous behavior, we show
      that the variation of entropy remains always positive in accordance with the
      second law of thermodynamics. 

PMID- 25770526
TI  - Partial secular Bloch-Redfield master equation for incoherent excitation of
      multilevel quantum systems.
AB  - We present an efficient theoretical method for calculating the time evolution of
      the density matrix of a multilevel quantum system weakly interacting with
      incoherent light. The method combines the Bloch-Redfield theory with a partial
      secular approximation for one-photon coherences, resulting in a master equation
      that explicitly exposes the reliance on transition rates and the angles between
      transition dipole moments in the energy basis. The partial secular Bloch-Redfield
      master equation allows an unambiguous distinction between the regimes of quantum
      coherent vs. incoherent energy transfer under incoherent light illumination. The
      fully incoherent regime is characterized by orthogonal transition dipole moments
      in the energy basis, leading to a dynamical evolution governed by a coherence
      free Pauli-type master equation. The coherent regime requires non-orthogonal
      transition dipole moments in the energy basis and leads to the generation of
      noise-induced quantum coherences and population-to-coherence couplings. As a
      first application, we consider the dynamics of excited state coherences arising
      under incoherent light excitation from a single ground state and observe
      population-to-coherence transfer and the formation of non-equilibrium quasisteady
      states in the regime of small excited state splitting. Analytical expressions
      derived earlier for the V-type system [T. V. Tscherbul and P. Brumer, Phys. Rev.
      Lett. 113, 113601 (2014)] are found to provide a nearly quantitative description
      of multilevel excited-state populations and coherences in both the small- and
      large-molecule limits. 

PMID- 25770527
TI  - Utilizing fast multipole expansions for efficient and accurate quantum-classical
      molecular dynamics simulations.
AB  - Recently, a novel approach to hybrid quantum mechanics/molecular mechanics
      (QM/MM) molecular dynamics (MD) simulations has been suggested [Schworer et al.,
      J. Chem. Phys. 138, 244103 (2013)]. Here, the forces acting on the atoms are
      calculated by grid-based density functional theory (DFT) for a solute molecule
      and by a polarizable molecular mechanics (PMM) force field for a large solvent
      environment composed of several 10(3)-10(5) molecules as negative gradients of a
      DFT/PMM hybrid Hamiltonian. The electrostatic interactions are efficiently
      described by a hierarchical fast multipole method (FMM). Adopting recent progress
      of this FMM technique [Lorenzen et al., J. Chem. Theory Comput. 10, 3244 (2014)],
      which particularly entails a strictly linear scaling of the computational effort
      with the system size, and adapting this revised FMM approach to the computation
      of the interactions between the DFT and PMM fragments of a simulation system,
      here, we show how one can further enhance the efficiency and accuracy of such
      DFT/PMM-MD simulations. The resulting gain of total performance, as measured for
      alanine dipeptide (DFT) embedded in water (PMM) by the product of the gains in
      efficiency and accuracy, amounts to about one order of magnitude. We also
      demonstrate that the jointly parallelized implementation of the DFT and PMM-MD
      parts of the computation enables the efficient use of high-performance computing
      systems. The associated software is available online. 

PMID- 25770528
TI  - Description of spin-orbit coupling in excited states with two-component methods
      based on approximate coupled-cluster theory.
AB  - A generalization of the approximated coupled-cluster singles and doubles method
      and the algebraic diagrammatic construction scheme up to second order to two
      component spinors obtained from a relativistic Hartree-Fock calculation is
      reported. Computational results for zero-field splittings of atoms and monoatomic
      cations, triplet lifetimes of two organic molecules, and the spin-forbidden part
      of the UV/Vis absorption spectrum of tris(ethylenediamine)cobalt(III) are
      presented. 

PMID- 25770529
TI  - Cross-circularly polarized two-exciton states in one to three dimensions.
AB  - Biexciton and two-exciton dissociated states of Frenkel-type excitons are studied
      theoretically using an exciton tight-binding (TB) model including a polarization
      degree of freedom. Because the biexciton consists of two cross-circularly
      polarized excitons, an on-site interaction (V) between the two excitons should be
      considered in addition to a nearest-neighbor two-exciton attractive interaction
      (delta). Although there are an infinitely large number of combinations of V and
      delta providing the observed binding energy of a biexciton, the wave function of
      the biexciton and two-exciton dissociated states is nearly independent of these
      parameter sets. This means that all the two-exciton states are uniquely
      determined from the exciton TB model. There are a spatially symmetric and an
      antisymmetric biexciton state for a one-dimensional (1D) lattice and two
      symmetric and one antisymmetric biexciton states at most for two- (2D) and three
      dimensional (3D) lattices. In contrast, when the polarization degree of freedom
      is ignored, there is one biexciton state for 1D, 2D, and 3D lattices. For this
      study, a rapid and memory-saving calculation method for two-exciton states is
      extended to include the polarization degree of freedom. 

PMID- 25770530
TI  - Ab initio O(N) elongation-counterpoise method for BSSE-corrected interaction
      energy analyses in biosystems.
AB  - An Elongation-counterpoise (ELG-CP) method was developed for performing accurate
      and efficient interaction energy analysis and correcting the basis set
      superposition error (BSSE) in biosystems. The method was achieved by combining
      our developed ab initio O(N) elongation method with the conventional counterpoise
      method proposed for solving the BSSE problem. As a test, the ELG-CP method was
      applied to the analysis of the DNAs' inter-strands interaction energies with
      respect to the alkylation-induced base pair mismatch phenomenon that causes a
      transition from G?C to A?T. It was found that the ELG-CP method showed high
      efficiency (nearly linear-scaling) and high accuracy with a negligibly small
      energy error in the total energy calculations (in the order of 10(-7)-10(-8)
      hartree/atom) as compared with the conventional method during the counterpoise
      treatment. Furthermore, the magnitude of the BSSE was found to be ca. -290
      kcal/mol for the calculation of a DNA model with 21 base pairs. This emphasizes
      the importance of BSSE correction when a limited size basis set is used to study
      the DNA models and compare small energy differences between them. In this work,
      we quantitatively estimated the inter-strands interaction energy for each
      possible step in the transition process from G?C to A?T by the ELG-CP method. It
      was found that the base pair replacement in the process only affects the
      interaction energy for a limited area around the mismatch position with a few
      adjacent base pairs. From the interaction energy point of view, our results
      showed that a base pair sliding mechanism possibly occurs after the alkylation of
      guanine to gain the maximum possible number of hydrogen bonds between the bases.
      In addition, the steps leading to the A?T replacement accompanied with
      replications were found to be unfavorable processes corresponding to ca. 10
      kcal/mol loss in stabilization energy. The present study indicated that the ELG
      CP method is promising for performing effective interaction energy analyses in
      biosystems. 

PMID- 25770531
TI  - Improving the efficiency of hierarchical equations of motion approach and
      application to coherent dynamics in Aharonov-Bohm interferometers.
AB  - Several recent advancements for the hierarchical equations of motion (HEOM)
      approach are reported. First, we propose an a priori estimate for the optimal
      number of basis functions for the reservoir memory decomposition. Second, we make
      use of the sparsity of auxiliary density operators (ADOs) and propose two ansatzs
      to screen out all the intrinsic zero ADO elements. Third, we propose a new
      truncation scheme by utilizing the time derivatives of higher-tier ADOs. These
      novel techniques greatly reduce the memory cost of the HEOM approach, and thus
      enhance its efficiency and applicability. The improved HEOM approach is applied
      to simulate the coherent dynamics of Aharonov-Bohm double quantum dot
      interferometers. Quantitatively accurate dynamics is obtained for both
      noninteracting and interacting quantum dots. The crucial role of the quantum
      phase for the magnitude of quantum coherence and quantum entanglement is
      revealed. 

PMID- 25770532
TI  - NMR diffusion-encoding with axial symmetry and variable anisotropy:
      Distinguishing between prolate and oblate microscopic diffusion tensors with
      unknown orientation distribution.
AB  - We introduce a nuclear magnetic resonance method for quantifying the shape of
      axially symmetric microscopic diffusion tensors in terms of a new diffusion
      anisotropy metric, DDelta, which has unique values for oblate, spherical, and
      prolate tensor shapes. The pulse sequence includes a series of equal-amplitude
      magnetic field gradient pulse pairs, the directions of which are tailored to give
      an axially symmetric diffusion-encoding tensor b with variable anisotropy bDelta.
      Averaging of data acquired for a range of orientations of the symmetry axis of
      the tensor b renders the method insensitive to the orientation distribution
      function of the microscopic diffusion tensors. Proof-of-principle experiments are
      performed on water in polydomain lyotropic liquid crystals with geometries that
      give rise to microscopic diffusion tensors with oblate, spherical, and prolate
      shapes. The method could be useful for characterizing the geometry of fluid
      filled compartments in porous solids, soft matter, and biological tissues. 

PMID- 25770533
TI  - Shape-independent model (SHIM) approach for studying aggregation by NMR
      diffusometry.
AB  - NMR diffusometry has been gaining wide popularity in various areas of applied
      chemistry for investigating diffusion and complexation processes in solid and
      aqueous phases. To date, the application of this method to study aggregation
      phenomena proceeding beyond the dimer stage of assembly has been restricted by
      the need for a priori knowledge of the aggregates' shape, commonly difficult to
      know in practice. We describe here a comprehensive analysis of aggregation
      parameter-dependency on the type and shape selected for modeling assembly
      processes, and report for the first time a shape-independent model (designated
      the SHIM approach), which may be used as an alternative in cases when information
      on aggregates' shapes is unavailable. The model can be used for determining
      equilibrium aggregation parameters from self-diffusion NMR data including
      equilibrium self-association constant and changes in enthalpy, DeltaH, and
      entropy, DeltaS. 

PMID- 25770534
TI  - Coarse-grained picture of Brownian motion in water: Role of size and interaction
      distance range on the nature of randomness.
AB  - The Brownian motion of a particle in a fluid is often described by the linear
      Langevin equation, in which it is assumed that the mass of the particle is
      sufficiently large compared to the surrounding fluid molecules. This assumption
      leads to a diffusion coefficient that is independent of the particle mass. The
      Stokes-Einstein equation indicates that the diffusion coefficient depends solely
      on the particle size, but the concept of size can be ambiguous when close to the
      molecular scale. We first examine the Brownian motion of simple model particles
      based on short-range interactions in water by the molecular dynamics method and
      show that the diffusion coefficient can vary with mass when this mass is
      comparable to that of the solvent molecules, and that this effect is evident when
      the solute particle size is sufficiently small. We then examine the properties of
      a water molecule considered as a solute in the bulk solvent consisting of the
      remainder of the water. A comparison with simple solute models is used to clarify
      the role of force fields. The long-range Coulomb interaction between water
      molecules is found to lead to a Gaussian force distribution in spite of a mass
      ratio and nominal size ratio of unity, such that solutes with short-range
      interactions exhibit non-Gaussian force distribution. Thus, the range of the
      interaction distance determines the effective size even if it does not represent
      the volume excluded by the repulsive force field. 

PMID- 25770535
TI  - Potential energy surfaces for the HBr(+) + CO2 -> Br + HOCO(+) reaction in the
      HBr(+)  (2)Pi3/2 and (2)Pi1/2 spin-orbit states.
AB  - Quantum mechanical (QM) + molecular mechanics (MM) models are developed to
      represent potential energy surfaces (PESs) for the HBr(+) + CO2 -> Br + HOCO(+)
      reaction with HBr(+) in the (2)Pi3/2 and (2)Pi1/2 spin-orbit states. The QM
      component is the spin-free PES and spin-orbit coupling for each state is
      represented by a MM-like analytic potential fit to spin-orbit electronic
      structure calculations. Coupled-cluster single double and perturbative triple
      excitation (CCSD(T)) calculations are performed to obtain "benchmark" reaction
      energies without spin-orbit coupling. With zero-point energies removed, the
      "experimental" reaction energy is 44 +/- 5 meV for HBr(+)((2)Pi3/2) + CO2 ->
      Br((2)P3/2) + HOCO(+), while the CCSD(T) value with spin-orbit effects included
      is 87 meV. Electronic structure calculations were performed to determine
      properties of the BrHOCO(+) reaction intermediate and [HBr?OCO](+) van der Waals
      intermediate. The results of different electronic structure methods were compared
      with those obtained with CCSD(T), and UMP2/cc-pVTZ/PP was found to be a practical
      and accurate QM method to use in QM/MM direct dynamics simulations. The spin
      orbit coupling calculations show that the spin-free QM PES gives a quite good
      representation of the shape of the PES originated by (2)Pi3/2HBr(+). This is also
      the case for the reactant region of the PES for (2)Pi1/2 HBr(+), but spin-orbit
      coupling effects are important for the exit-channel region of this PES. A MM
      model was developed to represent these effects, which were combined with the spin
      free QM PES. 

PMID- 25770536
TI  - A configurational study of helium clusters doped with He(*-) and He2(*-).
AB  - Helium clusters doped with electronically excited atomic and molecular helium
      anions He(*-) and He2(*-) at T = 0.4 K are studied by means of path integral
      Monte Carlo calculations. Geometry and energetics of the systems with up to 32
      solvating He atoms are characterised. The interactions between the anions and the
      neutral He atoms have been described by fitting previously reported ab initio
      points to analytical expressions. The HeN-He(*-) clusters with N > 6 display a
      structure defined by a bipyramid which completely solvates the atomic anion,
      whereas the rest of surrounding He atoms form a dimple around that initial cage.
      On the contrary, the structures observed for the HeN-He2(*-) clusters clearly
      show the dopant located outside the helium droplet, thereby confirming the
      heliophobic character of He2(*-).

PMID- 25770537
TI  - Electron collisions with phenol: Total, integral, differential, and momentum
      transfer cross sections and the role of multichannel coupling effects on the
      elastic channel.
AB  - We report theoretical and experimental total cross sections for electron
      scattering by phenol (C6H5OH). The experimental data were obtained with an
      apparatus based in Madrid and the calculated cross sections with two different
      methodologies, the independent atom method with screening corrected additivity
      rule (IAM-SCAR), and the Schwinger multichannel method with pseudopotentials
      (SMCPP). The SMCPP method in the Nopen-channel coupling scheme, at the static
      exchange-plus-polarization approximation, is employed to calculate the scattering
      amplitudes at impact energies ranging from 5.0 eV to 50 eV. We discuss the
      multichannel coupling effects in the calculated cross sections, in particular how
      the number of excited states included in the open-channel space impacts upon the
      convergence of the elastic cross sections at higher collision energies. The IAM
      SCAR approach was also used to obtain the elastic differential cross sections
      (DCSs) and for correcting the experimental total cross sections for the so-called
      forward angle scattering effect. We found a very good agreement between our SMCPP
      theoretical differential, integral, and momentum transfer cross sections and
      experimental data for benzene (a molecule differing from phenol by replacing a
      hydrogen atom in benzene with a hydroxyl group). Although some discrepancies were
      found for lower energies, the agreement between the SMCPP data and the DCSs
      obtained with the IAM-SCAR method improves, as expected, as the impact energy
      increases. We also have a good agreement among the present SMCPP calculated total
      cross section (which includes elastic, 32 inelastic electronic excitation
      processes and ionization contributions, the latter estimated with the binary
      encounter-Bethe model), the IAM-SCAR total cross section, and the experimental
      data when the latter is corrected for the forward angle scattering effect [Fuss
      et al., Phys. Rev. A 88, 042702 (2013)]. 

PMID- 25770538
TI  - Differential cross sections for electron impact excitation of the electronic
      bands of phenol.
AB  - We report results from a joint theoretical and experimental investigation into
      electron scattering from the important organic species phenol (C6H5OH).
      Specifically, differential cross sections (DCSs) have been measured and
      calculated for the electron-impact excitation of the electronic states of C6H5OH.
      The measurements were carried out at energies in the range 15-40 eV, and for
      scattered-electron angles between 10 degrees  and 90 degrees . The energy
      resolution of those experiments was typically ~80 meV. Corresponding Schwinger
      multichannel method with pseudo-potentials calculations, with and without Born
      closure, were also performed for a sub-set of the excited electronic-states that
      were accessed in the measurements. Those calculations were conducted at the
      static exchange plus polarisation (SEP)-level using a minimum orbital basis for
      single configuration interaction (MOBSCI) approach. Agreement between the
      measured and calculated DCSs was typically fair, although to obtain quantitative
      accord, the theory would need to incorporate even more channels into the MOBSCI.

PMID- 25770539
TI  - The interaction of He(-) with fullerenes.
AB  - The effects of interactions between He(-) and clusters of fullerenes in helium
      nanodroplets are described. Electron transfer from He(-) to (C60)n and (C70)n
      clusters results in the formation of the corresponding fullerene cluster
      dianions. This unusual double electron transfer appears to be concerted and is
      most likely guided by electron correlation between the two very weakly bound
      outer electrons in He(-). We suggest a mechanism which involves long range
      electron transfer followed by the conversion of He(+)into He2 (+), where
      formation of the He-He bond in He2 (+) releases sufficient kinetic energy for the
      cation and the dianion to escape their Coulombic attraction. By analogy with the
      corresponding dications, the observation of a threshold size of n >= 5 for
      formation of both (C60)n (2-) and (C70)n (2-) is attributed to Coulomb explosion
      rather than an energetic constraint. We also find that smaller dianions can be
      observed if water is added as a co-dopant. Other aspects of He(-) chemistry that
      are explored include its role in the formation of multiply charged fullerene
      cluster cations and the sensitivity of cluster dianion formation on the incident
      electron energy. 

PMID- 25770540
TI  - Nonadiabatic nuclear dynamics of the ammonia cation studied by surface hopping
      classical trajectory calculations.
AB  - The Landau-Zener (LZ) type classical-trajectory surface-hopping algorithm is
      applied to the nonadiabatic nuclear dynamics of the ammonia cation after
      photoionization of the ground-state neutral molecule to the excited states of the
      cation. The algorithm employs a recently proposed formula for nonadiabatic LZ
      transition probabilities derived from the adiabatic potential energy surfaces.
      The evolution of the populations of the ground state and the two lowest excited
      adiabatic states is calculated up to 200 fs. The results agree well with quantum
      simulations available for the first 100 fs based on the same potential energy
      surfaces. Three different time scales are detected for the nuclear dynamics:
      Ultrafast Jahn-Teller dynamics between the excited states on a 5 fs time scale;
      fast transitions between the excited state and the ground state within a time
      scale of 20 fs; and relatively slow partial conversion of a first-excited-state
      population to the ground state within a time scale of 100 fs. Beyond 100 fs, the
      adiabatic electronic populations are nearly constant due to a dynamic equilibrium
      between the three states. The ultrafast nonradiative decay of the excited-state
      populations provides a qualitative explanation of the experimental evidence that
      the ammonia cation is nonfluorescent. 

PMID- 25770541
TI  - Origin of the 900 cm(-1) broad double-hump OH vibrational feature of strongly
      hydrogen-bonded carboxylic acids.
AB  - Medium and strong hydrogen bonds are common in biological systems. Here, they
      provide structural support and can act as proton transfer relays to drive
      electron and/or energy transfer. Infrared spectroscopy is a sensitive probe of
      molecular structure and hydrogen bond strength but strongly hydrogen-bonded
      structures often exhibit very broad and complex vibrational bands. As an example,
      strong hydrogen bonds between carboxylic acids and nitrogen-containing aromatic
      bases commonly display a 900 cm(-1) broad feature with a remarkable double-hump
      structure. Although previous studies have assigned this feature to the OH, the
      exact origin of the shape and width of this unusual feature is not well
      understood. In this study, we present ab initio calculations of the contributions
      of the OH stretch and bend vibrational modes to the vibrational spectrum of
      strongly hydrogen-bonded heterodimers of carboxylic acids and nitrogen-containing
      aromatic bases, taking the 7-azaindole--acetic acid and pyridine--acetic acid
      dimers as examples. Our calculations take into account coupling between the OH
      stretch and bend modes as well as how both of these modes are affected by lower
      frequency dimer stretch modes, which modulate the distance between the monomers.
      Our calculations reproduce the broadness and the double-hump structure of the OH
      vibrational feature. Where the spectral broadness is primarily caused by the
      dimer stretch modes strongly modulating the frequency of the OH stretch mode, the
      double-hump structure results from a Fermi resonance between the out of the plane
      OH bend and the OH stretch modes.

PMID- 25770542
TI  - Theory vs. experiment for molecular clusters: Spectra of OCS trimers and
      tetramers.
AB  - All singly substituted (13)C, (18)O, and (34)S isotopomers of the previously
      known OCS trimer are observed in natural abundance in a broad-band spectrum
      measured with a chirped-pulse Fourier transform microwave spectrometer. The
      complete substitution structure thus obtained critically tests (and confirms) the
      common assumption that monomers tend to retain their free structure in a weakly
      bound cluster. A new OCS trimer isomer is also observed, and its structure is
      determined to be barrel-shaped but with the monomers all approximately aligned,
      in contrast to the original trimer which is barrel-shaped with two monomers
      aligned and one anti-aligned. An OCS tetramer spectrum is assigned for the first
      time, and the tetramer structure resembles an original trimer with an OCS monomer
      added at the end with two sulfur atoms. Infrared spectra observed in the region
      of the OCS nu1 fundamental (~2060 cm(-1)) are assigned to the same OCS tetramer,
      and another infrared band is tentatively assigned to a different tetramer isomer.
      The experimental results are compared and contrasted with theoretical predictions
      from the literature and from new cluster calculations which use an accurate OCS
      pair potential and assume pairwise additivity. 

PMID- 25770543
TI  - Rotation-vibration interactions in the spectra of polycyclic aromatic
      hydrocarbons: Quinoline as a test-case species.
AB  - Polycyclic aromatic hydrocarbons (PAHs) are highly relevant for astrophysics as
      possible, though controversial, carriers of the unidentified infrared emission
      bands that are observed in a number of different astronomical objects. In support
      of radio-astronomical observations, high resolution laboratory spectroscopy has
      already provided the rotational spectra in the vibrational ground state of
      several molecules of this type, although the rotational study of their dense
      infrared (IR) bands has only recently become possible using a limited number of
      experimental set-ups. To date, all of the rotationally resolved data have
      concerned unperturbed spectra. We presently report the results of a high
      resolution study of the three lowest vibrational states of quinoline C9H7N, an N
      bearing naphthalene derivative. While the pure rotational ground state spectrum
      of quinoline is unperturbed, severe complications appear in the spectra of the
      nu45 and nu44 vibrational modes (located at about 168 cm(-1) and 178 cm(-1),
      respectively). In order to study these effects in detail, we employed three
      different and complementary experimental techniques: Fourier-transform microwave
      spectroscopy, millimeter-wave spectroscopy, and Fourier-transform far-infrared
      spectroscopy with a synchrotron radiation source. Due to the high density of
      states in the IR spectra of molecules as large as PAHs, perturbations in the
      rotational spectra of excited states should be ubiquitous. Our study identifies
      for the first time this effect and provides some insights into an appropriate
      treatment of such perturbations. 

PMID- 25770544
TI  - Preparation of state purified beams of He, Ne, C, N, and O atoms.
AB  - The production and guiding of ground state and metastable C, N, and O atoms in a
      two-meter-long, bent magnetic guide are described. Pure beams of metastable
      He((3)S1) and Ne((3)P2), and of ground state N((4)S3/2) and O((3)P2) are obtained
      using an Even-Lavie valve paired with a dielectric barrier discharge or electron
      bombardment source. Under these conditions no electronically excited C, N, or O
      atoms are observed at the exit of the guide. A general valve with electron impact
      excitation creates, in addition to ground state atoms, electronically excited
      C((3)P2; (1)D2) and N((2)D5/2; (2)P3/2) species. The two experimental conditions
      are complimentary, demonstrating the usefulness of a magnetic guide in crossed or
      merged beam experiments such as those described in Henson et al. [Science 338,
      234 (2012)] and Jankunas et al. [J. Chem. Phys. 140, 244302 (2014)]. 

PMID- 25770545
TI  - Structural fluctuations and orientational glass of levoglucosan--High stability
      against ordering and absence of structural glass.
AB  - To investigate whether a non-exponential relaxation always indicates 2-4 nm-size
      regions of dynamic heterogeneity, we studied the kinetic freezing and unfreezing
      of structural fluctuations involving the rotational modes in orientationally
      disordered crystal (ODIC) of levoglucosan by calorimetry. The heat capacity, Cp,
      of levoglucosan measured over the 203 K-463 K range shows that its low
      temperature, orientationally ordered crystal (ORC) transforms to ODIC phase on
      heating, which then melts to a low viscosity liquid. On cooling, the melt
      transforms to the ODIC which then does not transform to the ORC. Instead, the
      ODIC supercools. Fluctuations resulting from hindered (random) rotations of
      levoglucosan molecules confined to the lattice sites and from their
      conformational changes become progressively slower on cooling and an
      orientational glass (O-G) forms showing the sigmoid shape decrease in Cp
      characteristic of structural arrest like that of a glass. On heating the O-G
      state, rotational fluctuations begin to contribute to Cp at To-g of 247.8 K and
      there is an overshoot in Cp and thermal hysteresis (characteristic of physical
      ageing) in the temperature range of 230-260 K. The non-exponential relaxation
      parameter, beta(cal), determined by fitting the Cp data to a non-exponential,
      nonlinear model for relaxation of a glass is 0.60, which is similar to beta(cal)
      found for polymers, molecular liquids, and metal-alloy melts in which Brownian
      diffusion occurs. Such beta(cal) < 1 are seen to indicate 2-4 nm-size dynamically
      heterogeneous domains in an ultraviscous liquid near the glass formation, but its
      value of 0.60 for ODIC levoglucosan, in which Brownian diffusion does not occur,
      would not indicate such domains. Despite the lack of Brownian diffusion, we
      discuss these findings in the potential energy landscape paradigm. Levoglucosan
      melt, which is believed to vitrify and to stabilize a protein's disordered
      structure, did not supercool even at 200 K/min cooling rate. The findings have
      consequences for reports on the dielectric relaxation studies that indicated that
      levoglucosan melt supercools to form a structural glass of Tg of ~245 K, and for
      computer simulation of its dynamics. Levoglucosan is the ninth ODIC that forms O
      G. It does so more easily than the other eight. 

PMID- 25770546
TI  - Scaling law for crystal nucleation time in glasses.
AB  - Due to high viscosity, glassy systems evolve slowly to the ordered state. Results
      of molecular dynamics simulation reveal that the structural ordering in glasses
      becomes observable over "experimental" (finite) time-scale for the range of phase
      diagram with high values of pressure. We show that the structural ordering in
      glasses at such conditions is initiated through the nucleation mechanism, and the
      mechanism spreads to the states at extremely deep levels of supercooling. We find
      that the scaled values of the nucleation time, tau1 (average waiting time of the
      first nucleus with the critical size), in glassy systems as a function of the
      reduced temperature, T~, are collapsed onto a single line reproducible by the
      power-law dependence. This scaling is supported by the simulation results for the
      model glassy systems for a wide range of temperatures as well as by the
      experimental data for the stoichiometric glasses at the temperatures near the
      glass transition. 

PMID- 25770547
TI  - Structure and stability of solid Xe(H2)n.
AB  - Mixtures of xenon and molecular hydrogen form a series of hexagonal, van der
      Waals compounds at high pressures and at 300 K. Synchrotron, x-ray, single
      crystal diffraction studies reveal that below 7.5 GPa, Xe(H2)8 crystallizes in a
      P3m1 structure that displays pressure-induced occupancy changes of two pairs of
      xenon atoms located on the 2c and 2d sites (while the third pair on yet another
      2c site remains fully occupied). The occupancy becomes 1 at the P3m1 to R3
      transition and all the xenon atoms occupy the 3d sites in the high-pressure
      structure. These pressure-induced changes in occupancy coincide with volume
      changes that maintain the average Xe:H2 stoichiometry fixed at 1:8. The
      synchrotron x-ray diffraction and Raman measurements show that this unique
      hydrogen-bearing compound that can be synthesized at 4.2 GPa and 300 K, quenched
      at low temperatures to atmospheric pressure, and retained up to 90 K on
      subsequent warming. 

PMID- 25770548
TI  - The glass-forming ability of model metal-metalloid alloys.
AB  - Bulk metallic glasses (BMGs) are amorphous alloys with desirable mechanical
      properties and processing capabilities. To date, the design of new BMGs has
      largely employed empirical rules and trial-and-error experimental approaches. Ab
      initio computational methods are currently prohibitively slow to be practically
      used in searching the vast space of possible atomic combinations for bulk glass
      formers. Here, we perform molecular dynamics simulations of a coarse-grained,
      anisotropic potential, which mimics interatomic covalent bonding, to measure the
      critical cooling rates for metal-metalloid alloys as a function of the atomic
      size ratio sigmaS/sigmaL and number fraction xS of the metalloid species. We show
      that the regime in the space of sigmaS/sigmaL and xS where well-mixed, optimal
      glass formers occur for patchy and LJ particle mixtures, coincides with that for
      experimentally observed metal-metalloid glass formers. Thus, our simple
      computational model provides the capability to perform combinatorial searches to
      identify novel glass-forming alloys. 

PMID- 25770549
TI  - Fluctuation-dissipation theorem and the dielectric response in supercooled
      liquids.
AB  - We consider the correlation between static conductivity and dynamic dielectric
      relaxation in a number of polar organic liquids. Experimental evidence suggests
      that in the simple cases the linear dependence between characteristic frequency
      of relaxation process and the value of static susceptibility is observed.
      However, this proportionality can be broken due to the appearance of additional
      relaxation processes (secondary or high-frequency ones) so it can be confused
      with the "fractional" variant of Debye-Stokes-Einstein relation. 

PMID- 25770550
TI  - Diffusivity and short-time dynamics in two models of silica.
AB  - We discuss the dynamic behavior of two silica models, the BKS model (by van
      Beest, Kramer, and van Santen) and the WAC model (by Woodcock, Angell, and
      Cheeseman). Although BKS is considered the more realistic model for liquid
      silica, the WAC model has the unique property that it is very close to having a
      liquid-liquid critical point (LLCP), and this makes it particularly useful in
      studying the dynamics of models that do have a LLCP. We find that the diffusivity
      is a good indicator of how close a liquid is to criticality--the Si diffusivity
      shows a jump of 3-4 orders of magnitude when the pressure is reduced, which may
      be interpreted as an abrupt (though not first-order) transition from a high
      density liquid state to a low-density liquid state. We show that this transition
      is captured by the Adam-Gibbs relation, which also allows us to estimate the
      configurational entropy of the system.

PMID- 25770551
TI  - Mechanism of the Cassie-Wenzel transition via the atomistic and continuum string
      methods.
AB  - The string method is a general and flexible strategy to compute the most probable
      transition path for an activated process (rare event). We apply here the
      atomistic string method in the density field to the Cassie-Wenzel transition, a
      central problem in the field of superhydrophobicity. We discuss in detail the
      mechanism of wetting of a submerged hydrophobic cavity of nanometer size and its
      dependence on the geometry of the cavity. Furthermore, we analyze the algorithmic
      analogies between the continuum "interface" string method and CREaM [Giacomello
      et al., Phys. Rev. Lett. 109, 226102 (2012)], a method inspired by the string
      that allows for a faster and simpler computation of the mechanism and of the free
      energy profiles of the wetting process. 

PMID- 25770552
TI  - N2 dissociation on W(110): An ab initio molecular dynamics study on the effect of
      phonons.
AB  - Accurately modeling the chemisorption dynamics of N2 on metal surfaces is of both
      practical and fundamental interest. The factors that may have hampered this
      achievement so far are the lack of an accurate density functional and the use of
      approximate methods to deal with surface phonons and non-adiabatic effects. In
      the current work, the dissociation of molecular nitrogen on W(110) has been
      studied using ab initio molecular dynamics (AIMD) calculations, simulating both
      surface temperature effects, such as lattice distortion, and surface motion
      effects, like recoil. The forces were calculated using density functional theory,
      and two density functionals were tested, namely, the Perdew-Burke-Ernzerhof (PBE)
      and the revised PBE (RPBE) functionals. The computed dissociation probability
      considerably differs from earlier static surface results, with AIMD predicting a
      much larger contribution of the indirect reaction channel, in which molecules
      dissociate after being temporally trapped in the proximity of the surface.
      Calculations suggest that the surface motion effects play a role here, since the
      energy transfer to the lattice does not allow molecules that have been trapped
      into potential wells close to the surface to find their way back to the gas
      phase. In comparison to experimental data, AIMD results overestimate the
      dissociation probability at the lowest energies investigated, where trapping
      dominates, suggesting a failure of both tested exchange-correlation functionals
      in describing the potential energy surface in the area sampled by trapped
      molecules. 

PMID- 25770553
TI  - Relationships between the surface electronic and chemical properties of doped 4d
      and 5d late transition metal dioxides.
AB  - Density functional theory calculations were performed to elucidate the underlying
      physics describing the adsorption energies on doped late transition metal dioxide
      rutiles. Adsorption energies of atomic oxygen on doped rutiles M(D)-M(H)O2, where
      transition metal M(D) is doped into M(H)O2, were expressed in terms of a
      contribution from adsorption on the pure oxide of the dopant M(D) and
      perturbations to this adsorption energy caused by changing its neighboring metal
      cations and lattice parameters to that of the host oxide M(H)O2, which we call
      the ligand and strain effects, respectively. Our analysis of atom projected
      density of states revealed that the t2g-band center had the strongest correlation
      with adsorption energies. We show that charge transfer mediated shifts to the t2g
      band center describe the ligand effect, and the radii of the atomic orbitals of
      metal cations can predict the magnitude and direction of this charge transfer.
      Strain produces systematic shifts to all features of the atom projected density
      of states, but correlations between the strain effect and the electronic
      structure were dependent on the chemical identity of the metal cation. The slope
      of these correlations can be related to the idealized d-band filling. This work
      elucidates the underlying physics describing adsorption on doped late transition
      metal oxides and establishes a foundation for models that use known chemical
      properties for the prediction of reactivity. 

PMID- 25770554
TI  - Systematic comparison of crystalline and amorphous phases: Charting the landscape
      of water structures and transformations.
AB  - Systematically resolving different crystalline phases starting from the atomic
      positions, a mandatory step in algorithms for the prediction of structures or for
      the simulation of phase transitions, can be a non-trivial task. Extending to
      amorphous phases and liquids which lack the discrete symmetries, the problem
      becomes even more difficult, involving subtle topological differences at medium
      range that, however, are crucial to the physico-chemical and spectroscopic
      properties of the corresponding materials. Typically, system-tailored order
      parameters are devised, like global or local symmetry indicators, ring
      populations, etc. We show that a recently introduced metric provides a simple and
      general solution to this intricate problem. In particular, we demonstrate that a
      map can be traced displaying distances among water phases, including crystalline
      as well as amorphous states and the liquid, consistently with experimental
      knowledge in terms of phase diagram, structural features, and preparation routes.

PMID- 25770555
TI  - On the theoretical description of weakly charged surfaces.
AB  - It is widely accepted that the Poisson-Boltzmann (PB) theory provides a valid
      description for charged surfaces in the so-called weak coupling limit. Here, we
      show that the image charge repulsion creates a depletion boundary layer that
      cannot be captured by a regular perturbation approach. The correct weak-coupling
      theory must include the self-energy of the ion due to the image charge
      interaction. The image force qualitatively alters the double layer structure and
      properties, and gives rise to many non-PB effects, such as nonmonotonic
      dependence of the surface energy on concentration and charge inversion. In the
      presence of dielectric discontinuity, there is no limiting condition for which
      the PB theory is valid. 

PMID- 25770556
TI  - Inclusion of line tension effect in classical nucleation theory for heterogeneous
      nucleation: A rigorous thermodynamic formulation and some unique conclusions.
AB  - A rigorous thermodynamic formulation of the geometric model for heterogeneous
      nucleation including line tension effect is missing till date due to the
      associated mathematical hurdles. In this work, we develop a novel thermodynamic
      formulation based on Classical Nucleation Theory (CNT), which is supposed to
      illustrate a systematic and a more plausible analysis for the heterogeneous
      nucleation on a planar surface including the line tension effect. The appreciable
      range of the critical microscopic contact angle (thetac), obtained from the
      generalized Young's equation and the stability analysis, is thetainfinity <
      thetac < theta' for positive line tension and is thetaM < thetac < thetainfinity
      for negative line tension. thetainfinity is the macroscopic contact angle, theta'
      is the contact angle for which the Helmholtz free energy has the minimum value
      for the positive line tension, and thetaM is the local minima of the
      nondimensional line tension effect for the negative line tension. The shape
      factor f, which is basically the dimensionless critical free energy barrier,
      becomes higher for lower values of thetainfinity and higher values of thetac for
      positive line tension. The combined effect due to the presence of the triple line
      and the interfacial areas (f(L) + f(S)) in shape factor is always within (0,
      3.2), resulting f in the range of (0, 1.7) for positive line tension. A formerly
      presumed appreciable range for thetac(0 < thetac < thetainfinity) is found not to
      be true when the effect of negative line tension is considered for CNT.
      Estimation based on the property values of some real fluids confirms the
      relevance of the present analysis. 

PMID- 25770557
TI  - Solutes at the liquid:liquid phase boundary--Solubility and solvent
      conformational response alter interfacial microsolvation.
AB  - A detailed understanding of solvent structure and dynamics at liquid:liquid
      interfaces is a necessary precursor for control and manipulation of these phase
      boundaries. Experimentally, amphiphilic solutes are often used to alter transport
      properties across water:organic interfaces; however, a fundamental model for the
      mechanism of this action has not been determined. This work compares the
      solvation profiles of ampiphilic solutes that traverse the phase boundary in
      binary water:n-hexane, and the individual microsolvation processes for
      interfacial water and hexane molecules therein. Microsolvation is defined as the
      rare event where one solvent molecule temporarily penetrates the co-solvent
      phases and is fully solvated therein. The solutes tri-butyl phosphate (TBP),
      hydrogen di-butyl phosphate, and di-hydrogen mono-butyl phosphate have been
      examined as they exhibit a systematic increase in aqueous solubility and
      selectively partition to the interfacial region at the infinite dilution limit.
      The relationship between adopted configurations of the solute, orientation of the
      solvent, and the ability of the solute to enhance microsolvation, specifically
      the ability of n-hexane to penetrate the aqueous phase, is demonstrated within a
      20 A radius of TBP. 

PMID- 25770558
TI  - Single atom catalysts on amorphous supports: A quenched disorder perspective.
AB  - Phenomenological models that invoke catalyst sites with different adsorption
      constants and rate constants are well-established, but computational and
      experimental methods are just beginning to provide atomically resolved details
      about amorphous surfaces and their active sites. This letter develops a
      statistical transformation from the quenched disorder distribution of site
      structures to the distribution of activation energies for sites on amorphous
      supports. We show that the overall kinetics are highly sensitive to the precise
      nature of the low energy tail in the activation energy distribution. Our analysis
      motivates further development of systematic methods to identify and understand
      the most reactive members of the active site distribution. 

PMID- 25770559
TI  - Thermodynamics of the adsorption of flexible polymers on nanowires.
AB  - Generalized-ensemble simulations enable the study of complex adsorption scenarios
      of a coarse-grained model polymer near an attractive nanostring, representing an
      ultrathin nanowire. We perform canonical and microcanonical statistical analyses
      to investigate structural transitions of the polymer and discuss their dependence
      on the temperature and on model parameters such as effective wire thickness and
      attraction strength. The result is a complete hyperphase diagram of the polymer
      phases, whose locations and stability are influenced by the effective material
      properties of the nanowire and the strength of the thermal fluctuations. Major
      structural polymer phases in the adsorbed state include compact droplets attached
      to or wrapping around the wire, and tubelike conformations with triangular
      pattern that resemble ideal boron nanotubes. The classification of the
      transitions is performed by microcanonical inflection-point analysis. 

PMID- 25770560
TI  - Compressed exponential decays in correlation experiments: The influence of
      temperature gradients and convection.
AB  - In a wide range of soft materials, correlation experiments using laser light or
      partially coherent X-rays report the so called compressed exponential correlation
      functions, i. e., decays c(t) ? exp(-(t/tau)(beta)) with beta > 1. In many cases,
      this is related to the relaxation of inner stresses, but in some systems, the
      source of such a phenomenon is still poorly understood. We performed multi
      speckle-dynamic light scattering experiments in a system of polystyrene spheres
      in supercooled propanediol. At low temperatures, compressed exponential decays
      are observed in a multispeckle experiment, in agreement with the literature
      findings in similar systems. At the same time, due to the particular geometry of
      our setup, the speckle pattern shows indication for convection in the sample due
      to a slight temperature gradient across the sample cuvette mounted in a cold
      finger cryostat. These effects increase with decreasing temperature and after a
      temperature jump. In some cases it can be corrected for by assuming convective
      flow at constant velocity. Such corrections reduce or remove compressed
      exponential behavior in our experiment. 

PMID- 25770561
TI  - Machine learning of single molecule free energy surfaces and the impact of
      chemistry and environment upon structure and dynamics.
AB  - The conformational states explored by polymers and proteins can be controlled by
      environmental conditions (e.g., temperature, pressure, and solvent) and molecular
      chemistry (e.g., molecular weight and side chain identity). We introduce an
      approach employing the diffusion map nonlinear machine learning technique to
      recover single molecule free energy landscapes from molecular simulations,
      quantify changes to the landscape as a function of external conditions and
      molecular chemistry, and relate these changes to modifications of molecular
      structure and dynamics. In an application to an n-eicosane chain, we quantify the
      thermally accessible chain configurations as a function of temperature and
      solvent conditions. In an application to a family of polyglutamate-derivative
      homopeptides, we quantify helical stability as a function of side chain length,
      resolve the critical side chain length for the helix-coil transition, and expose
      the molecular mechanisms underpinning side chain-mediated helix stability. By
      quantifying single molecule responses through perturbations to the underlying
      free energy surface, our approach provides a quantitative bridge between
      experimentally controllable variables and microscopic molecular behavior, guiding
      and informing rational engineering of desirable molecular structure and function.

PMID- 25770562
TI  - Theory and simulations of toroidal and rod-like structures in single-molecule DNA
      condensation.
AB  - DNA condensation by multivalent cations plays a crucial role in genome packaging
      in viruses and sperm heads, and has been extensively studied using single
      molecule experimental methods. In those experiments, the values of the critical
      condensation forces have been used to estimate the amplitude of the attractive
      DNA-DNA interactions. Here, to describe these experiments, we developed an
      analytical model and a rigid body Langevin dynamics assay to investigate the
      behavior of a polymer with self-interactions, in the presence of a traction force
      applied at its extremities. We model self-interactions using a pairwise
      attractive potential, thereby treating the counterions implicitly. The analytical
      model allows to accurately predict the equilibrium structures of toroidal and rod
      like condensed structures, and the dependence of the critical condensation force
      on the DNA length. We find that the critical condensation force depends strongly
      on the length of the DNA, and finite-size effects are important for molecules of
      length up to 10(5)MUm. Our Langevin dynamics simulations show that the force
      extension behavior of the rod-like structures is very different from the toroidal
      ones, so that their presence in experiments should be easily detectable. In
      double-stranded DNA condensation experiments, the signature of the presence of
      rod-like structures was not unambiguously detected, suggesting that the
      polyamines used to condense DNA may protect it from bending sharply as needed in
      the rod-like structures. 

PMID- 25770563
TI  - Comment on "The gas-liquid surface tension of argon: A reconciliation between
      experiment and simulation" [J. Chem. Phys. 140, 244710 (2014)].

PMID- 25770564
TI  - Response to "Comment on 'The gas-liquid surface tension of argon: A
      reconciliation between experiment and simulation"' [J. Chem. Phys. 142, 107101
      (2015)].

PMID- 25770565
TI  - Comment on "A model for phosphate glass topology considering the modifying ion
      sub-network" [J. Chem. Phys. 140, 154501 (2014)].
AB  - In a recent paper, Hermansen, Mauro, and Yue [J. Chem. Phys. 140, 154501 (2014)]
      applied the temperature-dependent constraint theory to model both the glass
      transition temperature, Tg, and fragility, m, of a series of binary alkali
      phosphate glasses of the form R2OxP2O5 1-x, where R represents an alkali species.
      Key to their success seems to be the retention of linear constraints between the
      alkali ion (R(+)) and the non-bridging oxygens near Tg, which allows the model to
      mimic a supposed minimum for both Tg(x) and m(x) located near x = 0.2. However,
      the authors have overlooked several recent studies that clearly show there is no
      minimum in m(x). We argue that the retention of the alkali ion constraints at
      these temperatures is unjustified and question whether the model calculations can
      be revised to meet the actual experimental data. We also discuss alternative
      interpretations for the fragility based on two-state thermodynamics that can
      accurately account for its compositional dependence. 

PMID- 25770566
TI  - Response to "Comment on 'A model for phosphate glass topology considering the
      modifying ion sub-network"' [J. Chem. Phys. 142, 107103 (2015)].
AB  - In our recent paper [C. Hermansen, J. C. Mauro, and Y.-Z. Yue, J. Chem. Phys.
      140, 154501 (2014)], we applied temperature-dependent constraint theory to model
      the glass transition temperature (Tg) and liquid fragility index (m) of alkali
      phosphate glasses. Sidebottom commented on this paper concerning the m values
      obtained by differential scanning calorimetry (DSC) [D. L. Sidebottom, J. Chem.
      Phys. 142, ? (2015)]. We have considered Sidebottom's comments carefully and
      conclude that the m values of phosphate liquids obtained by DSC are reliable,
      except for the NaPO3 and possibly P2O5 compositions. Based on his dynamic light
      scattering measurements, Sidebottom has found that P2O5 is a strong liquid with m
      ~ 20. However, based on the heat capacity jump at Tg and the stretching exponent
      of the relaxation function, P2O5 should be classified as an intermediate fragile
      liquid with m ~ 40. We also argue that m cannot be universally related to the
      average connectivity of the network and point out several inconsistencies with
      this view. 

PMID- 25770567
TI  - Comment on "An investigation of the liquid to glass transition using integral
      equations for the pair structure of coupled replicae" [J. Chem. Phys. 141, 174505
      (2014)].

PMID- 25770568
TI  - Erratum: "Phase diagram of ammonium nitrate" [J. Chem. Phys. 139, 214503 (2013)].

PMID- 25770569
TI  - Erratum: "Predicting the influence of long-range molecular interactions on
      macroscopic-scale diffusion by homogenization of the Smoluchowski equation" [J.
      Chem. Phys. 140, 174106 (2014)].

PMID- 25770570
TI  - Plantar fasciitis in Australian general practice.

PMID- 25770571
TI  - Paraesthesia and peripheral neuropathy.
AB  - BACKGROUND: Paraesthesia reflects an abnormality affecting the sensory pathways
      anywhere between the peripheral sensory nervous system and the sensory cortex. As
      with all neurology, the fundamental diagnostic tool is a concise history, devoid
      of potentially ambiguous jargon, which properly reflects the true nature of what
      the patient is experiencing, provocateurs, precipitating and relieving factors,
      concomitant illnesses, such as diabetes, and any treatments that could evoke
      neuropathies. OBJECTIVE: Some localised neuropathies, such as carpal tunnel
      syndrome (CTS) or ulnar neuropathy, produce classical features, such as weakness
      of the 'LOAF' (lateral two lumbricals, opponens pollicis, abductor pollicis
      brevis and flexor pollicis brevis) median innervated muscles, thereby obviating
      need for further neurophysiology. Nerve conduction studies may be necessary to
      diagnose peripheral neuropathy, but they may also be normal with small fibre
      neuropathy. Even with a diagnosis of peripheral neuropathy, definition of the
      underlying cause may remain elusive in a significant proportion of cases, despite
      involvement of consultants. DISCUSSION: Treatment is based on the relevant
      diagnosis and mechanism to address the cause. This includes better glycaemic
      control for diabetes, night splint for CTS or elbow padding for ulnar neuropathy,
      modifying lifestyle with reduced alcohol consumption or replacing dietary
      deficiencies or changing medications where appropriate and practical. Should such
      intervention fail to relieve symptoms, consideration of intervention to relieve
      symptoms of neuropathic pain may be required.

PMID- 25770572
TI  - Heel pain: a practical approach.
AB  - BACKGROUND: Heel pain is a common presentation in primary care and the risk of
      developing pain is higher with increasing body mass index and age.1 This is
      troubling given the increasing prevalence of obesity and an ageing population.
      OBJECTIVE: This article aims to assist with differential diagnosis of heel pain,
      which is critical as there are many structures in the heel area that can cause
      pain, and each requires a tailored treatment. DISCUSSION: Structures affected by
      pain vary with age, although the more common diagnoses such as Achilles
      insertional tendinopathy and plantar fascia pain can occur at any age. The use of
      diagnostic imaging must be considered in the context of clinical presentation as
      asymptomatic pathology occurs in many tissues. Evidence-based treatment for
      common causes of heel pain are limited. As with all presentations to clinicians,
      the potential for non-musculoskeletal, more sinister causes of pain and systemic
      disease must be considered.

PMID- 25770573
TI  - Ingrown toenails: the role of the GP.
AB  - BACKGROUND: An ingrown toenail or onychocryptosis may occur at any age and is the
      mostly commonly encountered toenail problem likely to be seen in general
      practice. OBJECTIVE: This article will discuss the common surgical approaches
      available for the management of an ingrown toenail. DISCUSSION: Ingrown toenail
      can be a painful condition that can become infected and may require surgical
      treatment. The epidemiology of onychocryptosis is difficult to determine as it is
      often considered to be a minor medical problem and as such has been some-what
      neglected in the literature. The few studies that have been conducted suggest a
      slightly higher male-to-female ratio, particularly in the 14-25 age group,4 but
      it can affect patients of any age. There are multiple reasons why an ingrown
      toenail will develop, including improper nail cutting technique, tight-fitting
      footwear, trauma, anatomical factors such as thickening of the nail plate, pincer
      shaped toenail, pressure from abutting digits caused by hallux valgus or lesser
      toe deformities, the presence of a subungual exostosis and, occasionally, the use
      of isotretinoin in the treatment of severe acne.

PMID- 25770574
TI  - The challenge of managing mid-foot pain.
AB  - BACKGROUND: The mid-foot bears the unheralded and proud, but potentially onerous,
      task of converting lower limb, vertically oriented stresses into propulsive
      horizontal motion with the further challenges of speed and direction change over
      varying terrains. A complex interaction of bones, joints and connective tissues
      has been cleverly engineered to accommodate these demands. However, these
      entrusted tissues will encounter acute traumatic stresses or cumulative micro
      stresses, leading to structural and functional deficits. OBJECTIVE: This article
      provides guidance in recognising and managing the key red flag conditions
      affecting the mid-foot region. Recent trends in imaging and medical management
      will also be outlined. DISCUSSION: With the exception of tibialis posterior
      dysfunction in the elderly, midfoot pain may not be a common presentation in
      general practice. It is important, therefore, to have a scheme of assessment and
      awareness of possible causes. In particular, the red flags of navicular stress
      fracture and Lisfranc ligament disruption require careful consideration as
      delayed care can result in poor outcomes.

PMID- 25770575
TI  - Evaluation of digital clubbing.

PMID- 25770576
TI  - Papilledema: a case of bilateral blurred vision caused by idiopathic intracranial
      hypertension.

PMID- 25770577
TI  - Disclosures of sexual abuse: what do you do next?
AB  - BACKGROUND: Sexual abuse, especially in childhood, often has severe and long
      lasting clinical consequences, both physical and psychological. OBJECTIVE: This
      article outlines an approach to use when patients disclose a history of sexual
      abuse, and provides some resources to call on in those circumstances. DISCUSSION:
      This article addresses questions one might ask to uncover a history of sexual
      abuse, possible responses to disclosures of sexual abuse, and documentation of
      these disclosures.

PMID- 25770578
TI  - Nipple pain associated with breastfeeding: incorporating current neurophysiology
      into clinical reasoning.
AB  - BACKGROUND: New mothers frequently experience breastfeeding problems, in
      particular nipple pain. This is often attributed to compression, skin damage,
      infection or dermatitis. OBJECTIVE: To outline an integrated approach to
      breastfeeding pain assessment that seeks to enhance current practice. DISCUSSION:
      Our clinical reasoning model resolves the complexity of pain into three
      categories: local stimulation, external influences and central modulation. Tissue
      pathology, damage or inflammation leads to local stimulation of nociceptors.
      External influences such as creams and breast pumps, as well as factors related
      to the mother, the infant and the maternal-infant interaction, may exacerbate the
      pain. Central nervous system modulation includes the enhancement of nociceptive
      transmission at the spinal cord and modification of the descending inhibitory
      influences. A broad range of factors can modulate pain through central mechanisms
      including maternal illness, exhaustion, lack of support, anxiety, depression or
      history of abuse. General practitioners (GPs) can use this model to explain
      nipple pain in complex settings, thus increasing management options for women.

PMID- 25770579
TI  - Cutaneous chemical burns: assessment and early management.
AB  - BACKGROUND: Chemical burns are common and may cause significant physical,
      psychological, social and economic burden. Despite a wide variety of potentially
      harmful chemicals, important general principals may be drawn in the assessment
      and initial management of such injuries. Early treatment of chemical burns is
      crucial and may reduce the period of resulting morbidity. OBJECTIVE: This article
      reviews the assessment and management of cutaneous chemical burns. DISCUSSION:
      Assessment of the patient should be rapid and occur in conjunction with early
      emergency management. Rapid history and pri-mary and secondary survey may be
      required to exclude systemic side effects of the injury. Depth of wound
      assessment is difficult given that necrosis caused by various chemicals can
      continue despite cessation of exposure. Early management should be conducted with
      consideration of clinician's safety, and appropriate precautions should be taken.
      Excluding specific situations and chemical exposure, copious irrigation with
      water remains the mainstay of early management. Referral to a centre of higher
      acuity may be required for expert evaluation.

PMID- 25770580
TI  - A comparison of vitamin D levels in two antenatal populations in regional Western
      Australia--'Tjindoo Ba Thonee Thurra': sunshine for the pregnant belly.
AB  - BACKGROUND: There is a known increased risk of vitamin D deficiency in darker
      skinned people living in in temperate latitudes, but there is limited literature
      specifically on Australian Aboriginal women and their vitamin D status in
      pregnancy. METHODS: This paper reports the findings of a prospective cohort study
      comparing vitamin D levels in a group of pregnant Aboriginal women with a group
      of pregnant non-Aboriginal women living in the same town in Western Australia.
      RESULTS: Aboriginal patients from the Aboriginal Community Controlled Health
      Service (ACCHS) had lower serum vitamin D levels (mean 46.7, SD 21.7 nmol/L),
      compared with their ?non-Aboriginal women (mean 65.4, SD 18.4 nmol/L, P
      CONCLUSION: We believe this is the first study to compare vitamin D levels in
      pregnant Aboriginal women with non-Aboriginal women living in the same community
      at temperate latitude.

PMID- 25770581
TI  - How general practitioners manage mental illness in culturally and linguistically
      diverse patients: an exploratory study.
AB  - BACKGROUND: General practitioners (GPs) see a range of mental illnesses and a
      diversity of patients, including patients from culturally and linguistically
      diverse (CALD) backgrounds. The aim of this study was to understand the barriers
      and facilitators GPs encounter when managing mental illness in CALD patients.
      METHODS: Semi-structured interviews with 10 Melbourne GPs were undertaken between
      May and July 2013. Data were analysed thematically. RESULTS: GP barriers included
      difficulties in recognising initial symptoms, communicating the diagnosis and
      using interpreter services. Facilitators included cultural concordance between
      the GP and patient, practice-based initiatives targeting CALD patients, and areas
      of further education for GPs and CALD patients. DISCUSSION: Cultural concordance
      between GPs and CALD patients is likely to be effective in facilitating
      management of mental illness. Further research is needed on interpreter use and
      scaling up practice-based initiatives to improve service delivery. At a
      population level, GPs thought it necessary to improve mental health literacy in
      CALD communities.

PMID- 25770582
TI  - A historical perspective of the barriers to generalism.
AB  - BACKGROUND: As early as the late 19th century, there were calls to give greater
      emphasis to general practice. The momentum picked up after the Second World War.
      The voices calling for more generalism reached a crescendo in the late 1960s.
      Optimism was very high in the following two decades. Today, there is a pervasive
      sense of lost opportunity as generalism continues to languish behind the
      increasing momentum of specialisation of medicine. OBJECTIVE: This article is a
      view of generalism through the lens of history. It seeks to understand and draw
      lessons from the slow progress of generalism in the light of the forces that have
      shaped its development through the years. DISCUSSION: The tensions between
      sectors that promote generalism continue to this day. The ongoing antagonism
      between the plough, the town and the gown remains a dominant factor that shapes
      the path to generalism. Political activism seems to be an effective tool in
      promoting greater generalism.

PMID- 25770583
TI  - Review of patents for microneedle application devices allowing fluid injections
      through the skin.
AB  - Microneedles have been developed in the past few years as a new means of
      transdermal drug delivery. They indeed present many advantages compared to
      injections using hypodermic needles (reduced risk of contamination and epidermic
      reactions), but mostly bring comfort and compliance to patients. Microneedles may
      be plain, opening pathways for medications to dissolve into the skin, or hollow,
      allowing fluid to actually enter the dermis or the hypodermis. This review
      focuses on the latter type of microneedles and two issues with their application:
      first, ensuring correct insertion into the skin (controlled and repeatable
      insertion depth, mainly); and second, ensuring correct fluid delivery to the
      dermis (controlled infusion rate). This paper thus focuses on recently published
      patents for hollow microneedle applicators-i.e., microneedles applicators that
      allow fluid delivery to the skin. Descriptions are given of several of the most
      relevant patents concerning this. The benefits and drawbacks of the different
      solutions are also described. 

PMID- 25770584
TI  - Che-1-induced inhibition of mTOR pathway enables stress-induced autophagy.
AB  - Mammalian target of rapamycin (mTOR) is a key protein kinase that regulates cell
      growth, metabolism, and autophagy to maintain cellular homeostasis. Its activity
      is inhibited by adverse conditions, including nutrient limitation, hypoxia, and
      DNA damage. In this study, we demonstrate that Che-1, a RNA polymerase II-binding
      protein activated by the DNA damage response, inhibits mTOR activity in response
      to stress conditions. We found that, under stress, Che-1 induces the expression
      of two important mTOR inhibitors, Redd1 and Deptor, and that this activity is
      required for sustaining stress-induced autophagy. Strikingly, Che-1 expression
      correlates with the progression of multiple myeloma and is required for cell
      growth and survival, a malignancy characterized by high autophagy response. 

PMID- 25770585
TI  - Smg6/Est1 licenses embryonic stem cell differentiation via nonsense-mediated mRNA
      decay.
AB  - Nonsense-mediated mRNA decay (NMD) is a post-transcriptional mechanism that
      targets aberrant transcripts and regulates the cellular RNA reservoir. Genetic
      modulation in vertebrates suggests that NMD is critical for cellular and tissue
      homeostasis, although the underlying mechanism remains elusive. Here, we generate
      knockout mice lacking Smg6/Est1, a key nuclease in NMD and a telomerase cofactor.
      While the complete loss of Smg6 causes mouse lethality at the blastocyst stage,
      inducible deletion of Smg6 is compatible with embryonic stem cell (ESC)
      proliferation despite the absence of telomere maintenance and functional NMD.
      Differentiation of Smg6-deficient ESCs is blocked due to sustained expression of
      pluripotency genes, normally repressed by NMD, and forced down-regulation of one
      such target, c-Myc, relieves the differentiation block. Smg6-null embryonic
      fibroblasts are viable as well, but are refractory to cellular reprograming into
      induced pluripotent stem cells (iPSCs). Finally, depletion of all major NMD
      factors compromises ESC differentiation, thus identifying NMD as a licensing
      factor for the switch of cell identity in the process of stem cell
      differentiation and somatic cell reprograming. 

PMID- 25770586
TI  - Modelling the coordination of the controls of stomatal aperture, transpiration,
      leaf growth, and abscisic acid: update and extension of the Tardieu-Davies model.
AB  - Stomatal aperture, transpiration, leaf growth, hydraulic conductance, and
      concentration of abscisic acid in the xylem sap ([ABA]xyl) vary rapidly with time
      of day. They follow deterministic relations with environmental conditions and
      interact in such a way that a change in any one of them affects all the others.
      Hence, approaches based on measurements of one variable at a given time or on
      paired correlations are prone to a confusion of effects, in particular for
      studying their genetic variability. A dynamic model allows the simulation of
      environmental effects on the variables, and of multiple feedbacks between them at
      varying time resolutions. This paper reviews the control of water movement
      through the plant, stomatal aperture and growth, and translates them into
      equations in a model. It includes recent progress in understanding the intrinsic
      and environmental controls of tissue hydraulic conductance as a function of
      transpiration rate, circadian rhythms, and [ABA]xyl. Measured leaf water
      potential is considered as the water potential of a capacitance representing
      mature tissues, which reacts more slowly to environmental cues than xylem water
      potential and expansive growth. Combined with equations for water and ABA fluxes,
      it results in a dynamic model able to simulate variables with genotype-specific
      parameters. It allows adaptive roles for hydraulic processes to be proposed, in
      particular the circadian oscillation of root hydraulic conductance. The script of
      the model, in the R language, is included together with appropriate documentation
      and examples.

PMID- 25770587
TI  - The dual nature of trehalose in citrus canker disease: a virulence factor for
      Xanthomonas citri subsp. citri and a trigger for plant defence responses.
AB  - Xanthomonas citri subsp. citri (Xcc) is a bacterial pathogen that causes citrus
      canker in susceptible Citrus spp. The Xcc genome contains genes encoding enzymes
      from three separate pathways of trehalose biosynthesis. Expression of genes
      encoding trehalose-6-phosphate synthase (otsA) and trehalose phosphatase (otsB)
      was highly induced during canker development, suggesting that the two-step
      pathway of trehalose biosynthesis via trehalose-6-phosphate has a function in
      pathogenesis. This pathway was eliminated from the bacterium by deletion of the
      otsA gene. The resulting XccDeltaotsA mutant produced less trehalose than the
      wild-type strain, was less resistant to salt and oxidative stresses, and was less
      able to colonize plant tissues. Gene expression and proteomic analyses of
      infected leaves showed that infection with XccDeltaotsA triggered only weak
      defence responses in the plant compared with infection with Xcc, and had less
      impact on the host plant's metabolism than the wild-type strain. These results
      suggested that trehalose of bacterial origin, synthesized via the otsA-otsB
      pathway, in Xcc, plays a role in modifying the host plant's metabolism to its own
      advantage but is also perceived by the plant as a sign of pathogen attack. Thus,
      trehalose biosynthesis has both positive and negative consequences for Xcc. On
      the one hand, it enables this bacterial pathogen to survive in the inhospitable
      environment of the leaf surface before infection and exploit the host plant's
      resources after infection, but on the other hand, it is a tell-tale sign of the
      pathogen's presence that triggers the plant to defend itself against infection. 

PMID- 25770588
TI  - Brassinosteroids are involved in Fe homeostasis in rice (Oryza sativa L.).
AB  - Brassinosteroids (BRs) are steroid hormones that modulate numerous physiological
      processes in plants. However, few studies have focused on the involvement of BRs
      in sensing and responding to the stress of mineral nutrient deficiency. In the
      present study, we evaluated the roles of BRs in the response of rice (Oryza
      sativa) to iron (Fe) deficiency during Fe uptake, transport, and translocation.
      Exogenous application of 24-epibrassinolide (EBR) to wild-type (WT) plants
      exaggerated leaf symptoms of Fe deficiency and suppressed growth. EBR increased
      and decreased Fe concentrations in roots and shoots, respectively, under both Fe
      deficient and Fe-sufficient conditions. Transcripts involved in Fe homeostasis,
      including OsIRT1, OsYSL15, OsYSL2, OsNAS1, and OsNAS2, were enhanced by EBR under
      Fe-deficient conditions. EBR depressed expression of OsNAS1, OsNAS2, and OsYSL2
      in shoots, and inhibited Fe transport and translocation via the phloem. Rice
      mutant d2-1, which is defective in BR biosynthesis, was more tolerant to Fe
      deficiency than the WT, and accumulated greater amounts of Fe in roots than the
      WT under Fe-sufficient conditions. A greater upregulation of OsIRT1, OsYSL15,
      OsYSL2, OsNAS1, and OsNAS2 in the d2-1 mutant compared to the WT was found under
      Fe-sufficient conditions, while expression of these genes in the d2-1 mutant was
      lower than in the WT under Fe-deficient conditions. The greater tolerance of the
      d2-1 mutant could be partly mitigated by exogenous application of EBR. These
      novel findings highlight the important role of BR in mediating the response of
      strategy II plants to Fe deficiency by regulating Fe uptake and translocation in
      rice. 

PMID- 25770589
TI  - Chronic obstructive pulmonary disease is a strong independent risk factor for
      osteoporosis and pathologic fractures: a population-based cohort study.

PMID- 25770590
TI  - Takayasu arteritis and ischaemic stroke.

PMID- 25770591
TI  - Chronic obstructive pulmonary disease is a strong independent risk factor for
      osteoporosis and pathologic fractures: a population-based cohort study.

PMID- 25770592
TI  - Crack lung: cocaine-induced lung injury.

PMID- 25770593
TI  - Acute airway compromise due to ruptured inferior thyroid artery aneurysm.
AB  - A cervical hematoma secondary to the spontaneous rupture of an aneurysm is an
      uncommon but catastrophic life-threatening condition because it can potentially
      obstruct the airway. Inferior thyroid artery aneurysm and rupture is a very rare
      clinical entity and only a limited number of cases have been reported in the
      literature. In this article, we present the case of a female patient who suffered
      from a rapidly enlarging cervical mass followed by a rapid onset of dyspnea as a
      result of rupture of an inferior thyroid artery aneurysm. The diagnosis was
      confirmed by magnetic resonance angiography, and delayed surgery resulted in an
      uneventful outcome. We aim to draw the attention of emergency physicians to this
      rare condition.

PMID- 25770594
TI  - Can differential regional ventilation protect the spared lung in acute
      respiratory distress syndrome?
AB  - Acute respiratory distress syndrome (ARDS) is a common clinical problem prevalent
      in intensive care settings. It can complicate many critical illnesses. The
      general treatment is mainly supportive. Mechanical ventilation, low tidal volume
      strategy, and control of plateau pressure form the basis of current management.
      No specific treatment exists for ARDS. Various interventions have been tested for
      the lethal condition including steroids, fluid restriction, statins, high
      frequency ventilation, nitric oxide, and prone ventilation strategy. However,
      none has shown improvement apart from prone positioning and low tidal volume
      ventilation. We report our observation in a patient with ARDS, which may
      potentially show a new mechanism to protect normal alveoli in ARDS lung and
      thereby may improve survival.

PMID- 25770596
TI  - Flavonoids in coronary heart disease.

PMID- 25770595
TI  - The effect of ethanol on lactate and base deficit as predictors of morbidity and
      mortality in trauma.
AB  - OBJECTIVE: The objective of this study was to assess the predictive value of
      lactate and base deficit in determining outcomes in trauma patients who are
      positive for ethanol. METHODS: Retrospective cohort study of patients admitted to
      a level 1 trauma center between 2005 and 2014. Adult patients who had a serum
      ethanol, lactate, base deficit, and negative urine drug screen obtained upon
      presentation were included. RESULTS: Data for 2482 patients were analyzed with
      1127 having an elevated lactate and 1092 an elevated base deficit. In these
      subgroups, patients with a positive serum ethanol had significantly lower 72-hour
      mortality, overall mortality, and hospital length of stay compared with the
      negative ethanol group. Abnormal lactate (odds ratio [OR], 2.607; 95% confidence
      interval [CI], 1.629-4.173; P = .000) and base deficit (OR, 1.917; 95% CI, 1.183
      3.105; P = .008) were determined to be the strongest predictors of mortality in
      the ethanol-negative patients. Injury Severity Score was found to be the lone
      predictor of mortality in patients positive for ethanol (OR, 1.104; 95% CI, 1.070
      1.138; P = .000). Area under the curve and Youden index analyses supported a
      relationship between abnormal lactate, base deficit, and mortality in ethanol
      positive patients when the serum lactate was greater than 4.45 mmol/L and base
      deficit was greater than -6.95 mmol/L. CONCLUSIONS: Previously established
      relationships between elevated lactate, base deficit, and outcome do not remain
      consistent in patients presenting with positive serum ethanol concentrations.
      Ethanol skews the relationship between lactate, base deficit, and mortality thus
      resetting the threshold in which lactate and base deficit are associated with
      increased mortality.

PMID- 25770597
TI  - Higher resistance of Campylobacter coli compared to Campylobacter jejuni at
      chicken slaughterhouse.
AB  - In order to compare the prevalence of Campylobacter coli and Campylobacter jejuni
      during the processing of broilers at slaughterhouse a total of 848 samples were
      analyzed during 2012 in southern Spain. Four hundred and seventy six samples were
      collected from cloaca, carcass surfaces and quartered carcasses. Moreover, 372
      environmental swabs from equipment and scalding water were collected. Minimum
      inhibitory concentration (MIC) to ciprofloxacin, erythromycin, streptomycin,
      tetracycline and gentamicin was determined for isolates from chicken meat. The
      general prevalence of Campylobacter was 68.8% (40.2% of C. coli and 28.5% of C.
      jejuni). The relative prevalence of C. coli increased from loading dock area
      (41.5%) to packing area (64.6%). In contrast, the relative prevalence of C.
      jejuni decreased from 58.5% to 35.4%. These differences between species from
      initial to final area were significant (p=0.02). The highest antimicrobial
      resistance for C. jejuni and C. coli was detected to tetracycline (100%) and
      ciprofloxacin (100%), respectively. Campylobacter coli showed an antimicrobial
      resistance significantly higher than C. jejuni to streptomycin (p=0.002) and
      erythromycin (p<0.0001). 

PMID- 25770600
TI  - On the coupling of hydride generation with atmospheric pressure glow discharge in
      contact with the flowing liquid cathode for the determination of arsenic,
      antimony and selenium with optical emission spectrometry.
AB  - The miniaturized atmospheric pressure glow discharge (APGD) sustained between a
      liquid flowing cathode and a He nozzle jet anode was combined with hydride
      generation (HG) to improve the performance of the determination of As, Sb and Se
      with optical emission spectrometry (OES). As(III), Sb(III) and Se(IV) species
      were converted into volatile hydrides in the reaction with NaBH4 and right after
      that they were delivered to the near-anode region of APGD through the nozzle. The
      transport efficiency of As, Sb and Se to the discharge was several times higher,
      while intensities of atomic emission lines of As, Sb and Se were improved 3
      orders of magnitude (as compared to intensities acquired for the near-cathode
      region in a APGD system with a typical introduction of analytes through
      sputtering of the flowing liquid cathode). The effect of the concentration of
      NaBH4 and HCl in a sample solution, the discharge current, the flow rate of He
      carrier/jet-supporting and He shielding gases on the emission yield coming from
      As, Sb, Se, He and H atomic lines and OH and N2 band heads as well as the
      electron number density was thoroughly studied. Under compromised conditions,
      limits of detection (3sigma criterion) of As, Sb and Se were respectively 4.2,
      1.2 and 3.1 ug L(-1). Usefulness of the method was confirmed by the analysis of
      Sniadecki and Marchlewski highly mineralized spring waters (Kudowa Zdroj, Poland)
      on the content of As, Sb and Se. Recoveries of elements added to these spring
      waters were within 90.3-103.7% proving good accuracy of the HG-APGD-OES method.

PMID- 25770598
TI  - Identification and characterization of Tu88, an antigenic gene from Theileria
      uilenbergi.
AB  - Theileria uilenbergi is a pathogen that causes ovine theileriosis. Prevention and
      control of theileriosis relies on its diagnosis at early stages of occurrence and
      requires understanding of proteins with antigenic properties from the pathogen.
      Despite its prevalence in China, only a few molecules with antigenic properties
      have been characterized from T. uilenbergi. In this study, we identified a cDNA
      named Tu88 by immunoscreening a T. uilenbergi merozoite cDNA library with T.
      uilenbergi-positive sera from infected sheep. Recombinant Tu88 (rTu88) expressed
      in bacteria reacted strongly with the positive sera of T. uilenbergi in western
      blot analysis indicating its potential as an antigen. Southern blot analysis
      showed that it is a single copy gene. Protein localization by immunostaining
      blood smears from an infected sheep demonstrated the presence of native Tu88 in
      merozoites. These findings suggest that Tu88 is a potential candidate antigen for
      the development of a sero-diagnostic tool. 

PMID- 25770599
TI  - Rapid and selective extraction of multiple macrolide antibiotics in foodstuff
      samples based on magnetic molecularly imprinted polymers.
AB  - Magnetic molecularly imprinted polymers (MMIPs) were prepared based on surface
      molecular imprinting using erythromycin (ERY) as template molecule and Fe3O4
      nanoparticles as support substrate. The MMIPs possessed high adsorption capacity
      of 94.1 mg/g for ERY and the imprinting factor was 11.9 indicating good imprinted
      effect for ERY. Selective evaluation demonstrated favorable selectivity of MMIPs
      for multiple macrolide antibiotics (MACs). Using MMIPs as adsorptive material, a
      rapid and convenient magnetic solid-phase extraction (MSPE) procedure was
      established for simultaneous and selective separation of six MACs in pork, fish
      and shrimp samples, then the MACs was subjected to high-performance liquid
      chromatography-ultraviolet (HPLC-UV) analysis. At different fortified
      concentrations, the extraction recoveries could reach 89.1% and the relative
      standard deviations were lower than 12.4%. Chromatogram revealed the response
      signals of MACs in spiked samples were greatly enhanced and matrix interferences
      were effectively eliminated after treatment with MSPE. The proposed MSPE
      procedure coupled with HPLC-UV realized selective and sensitive determination of
      multiple MACs in foodstuff samples.

PMID- 25770601
TI  - Anamperometric superoxide anion radicalbiosensor based on SOD/PtPd-PDARGO
      modified electrode.
AB  - In the present work, a high-performance enzyme-based electrochemical sensor for
      the detection of superoxide anion radical (O2(?-)) is reported. Firstly, we
      employed a facile approach to synthesize PtPd nanoparticles (PtPd NPs) on
      chemically reduced graphene oxide (RGO) coated with polydopamine (PDA). The
      prepared PtPd-PDARGO composite was well characterized by transmission electron
      microscopy, scanning electron microscopy, Fourier transform infrared spectra, X
      ray diffraction, X-ray photoelectron spectroscopy and electrochemical methods.
      Then the assembled composite was used as a desired electrochemcial interface for
      superoxide dismutase (SOD) immobilization. Owing to the PDA layer as well as the
      synergistic effect of PtPd NPs, the fabricated SOD/PtPd-PDARGO sensor exhibited
      an outstanding sensitivity of 909.7 MUA mM(-1) cm(-2) upon O2(?-) in a linear
      range from 0.016 mM to 0.24 mM (R(2)=0.992), with a low detection limit of 2 MUM
      (S/N=3) and excellent selectivity, good reproducibility as well as favorable long
      term stability.

PMID- 25770602
TI  - Redox speciation analysis of dissolved iron in estuarine and coastal waters with
      on-line solid phase extraction and graphite furnace atomic absorption
      spectrometry detection.
AB  - An automatic on-line solid phase extraction (SPE) system employing the flow
      injection (FI) technique directly coupled to a graphite furnace atomic absorption
      spectrometer (GFAAS) was established for speciation and determination of
      dissolved iron in estuarine and coastal waters. Fe(II) was mixed with ferrozine
      solution in a sample stream to form the Fe(II)-ferrozine complex which was
      extracted onto a C18 SPE cartridge, eluted with eluent and detected with GFAAS.
      In a parallel flow channel, Fe(III) was reduced to Fe(II) with ascorbic acid and
      then detected in the same way as Fe(II). The home-made interface between FI-SPE
      and GFAAS efficiently realized the sample introduction to the furnace in a semi
      automated way. Parameters of the FI-SPE system and graphite furnace program were
      optimized based on a univariate experimental design and an orthogonal array
      design. The salinity effect on the method sensitivity was investigated. The
      proposed method provided a detection limit of 1.38 nmol L(-1) for Fe(II) and 1.87
      nmol L(-1) for Fe(II+III). With variation of the sample loading volume, a
      broadened determination range of 2.5-200 nmol L(-1) iron could be obtained. The
      proposed method was successfully applied to analyze iron species in samples
      collected from the Jiulongjiang Estuary, Fujian, China. With the 2-cartridge FI
      SPE system developed, on-line simultaneous determination of Fe species with GFAAS
      was achieved for the first time.

PMID- 25770603
TI  - Ion pair-based dispersive liquid-liquid microextraction followed by high
      performance liquid chromatography as a new method for determining five folate
      derivatives in foodstuffs.
AB  - A novel technique for simultaneous determination of five folate derivatives in
      various food matrices was developed by ion pair-based dispersive liquid-liquid
      microextraction (IP-DLLME) combined with high-performance liquid chromatography
      (HPLC). In the proposed method, N-methyl-N,N-dioctyloctan-1-ammonium chloride
      (aliquat-336) was used as an ion-pair reagent. Effective variables of
      microextraction process were optimized. Under optimum conditions, the method
      yielded a linear calibration curve ranging from 1-200 ng g(-1) with correlation
      coefficients (r(2)) higher than 0.98. The relative standard deviation for the
      seven analyses was 5.2-7.4%. Enrichment factors for the five folates ranged
      between 108-135. Limits of detection were 2-4.1 ng g(-1). A comparison of this
      method with other methods described that the new proposed method is rapid and
      accurate, and gives very good enrichment factors and detection limits for
      determining five folate derivatives. The newly developed method was successfully
      applied for the determination of five folate derivatives in wheat flour, egg yolk
      and orange juice samples.

PMID- 25770604
TI  - A new highly selective fluorescent turn-on chemosensor for cyanide anion.
AB  - A new simple molecule, 2-((2-phenyl-2H-1,2,3-triazol-4-yl)methylene)malononitrile
      (M1), was synthesized successfully by the Knoevenagel condensation reaction
      between 2-phenyl-1,2,3-triazole-4-carboxaldehyde and malononitrile. The receptor
      M1 is highly sensitive and selective to cyanide anion due to the nucleophilic
      addition of cyanide anion with M1. Distinct changes on UV-vis and fluorescence
      spectra can be detected with the addition of cyanide anion to the DMSO solution
      of M1. Optical properties of M1 were scarcely affected by the addition of other
      common background anions (F(-), Cl(-), Br(-), I(-), SCN(-), OH(-), CO4(2-),
      H2PO4(-), SO4(2-), HSO4(-), AcO(-), and NO3(-)) under the same condition. The
      detection limit of CN(-) reaches ~1.43 MUM by M1 and the presence of background
      anions brought very slight interference for the detection of CN(-).

PMID- 25770605
TI  - Recent applications of hyperspectral imaging in microbiology.
AB  - Hyperspectral chemical imaging (HSI) is a broad term encompassing spatially
      resolved spectral data obtained through a variety of modalities (e.g. Raman
      scattering, Fourier transform infrared microscopy, fluorescence and near-infrared
      chemical imaging). It goes beyond the capabilities of conventional imaging and
      spectroscopy by obtaining spatially resolved spectra from objects at spatial
      resolutions varying from the level of single cells up to macroscopic objects
      (e.g. foods). In tandem with recent developments in instrumentation and sampling
      protocols, applications of HSI in microbiology have increased rapidly. This
      article gives a brief overview of the fundamentals of HSI and a comprehensive
      review of applications of HSI in microbiology over the past 10 years. Technical
      challenges and future perspectives for these techniques are also discussed. 

PMID- 25770606
TI  - Label-free detection of pathogenic bacteria via immobilized antimicrobial
      peptides.
AB  - A novel label-free strategy for the detection of bacteria was developed by using
      a specific antimicrobial peptide (AMP)-functionalized quartz crystal microbalance
      (QCM) electrode. This electrode interface was successfully applied to detect
      pathogenic Escherichia coli O157:H7 based on the specific affinity between the
      small synthetic antimicrobial peptide and the bacterial cell of pathogenic E.
      coli O157:H7. The concentrations of pathogenic E. coli O157:H7 were sensitively
      measured by the frequency response of the QCM with a detection limit of 0.4 cfu
      MUL(-1). The detection can be fulfilled within 10 min because it does not require
      germiculture process. On the other hand, if the specific antimicrobial peptides
      were immobilized on a gold electrode, this label-free strategy can also be
      performed by electrochemical impedance spectroscopy (EIS). Compared with QCM
      technique, the EIS measurement gives a lower sensitivity and needs a longer assay
      time. The combination of antimicrobial peptides with the real-time responses of
      QCM, as well as electronic read-out monitoring of EIS, may open a new way for the
      direct detection of bacteria.

PMID- 25770607
TI  - Inhibitive potentiometric detection of trace metals with ultrathin polypyrrole
      glucose oxidase biosensor.
AB  - A method, based on the inhibition of an ultrathin polypyrrole-glucose oxidase
      (PPy-GOx) potentiometric biosensor response, is described for the detection of
      Cu(2+), Hg(2+), Cd(2+) and Pb(2+) ions. Based on experimental conditions (0.2 M
      pyrrole, 500 U mL(-1) GOx, and an applied current density of 0.05 mA cm(-2) and a
      polymerization period of 500s) previously published by us, PPy-GOx films of
      approximately 55 nm thick were used to demonstrate the inhibitive potentiometric
      detection of selected trace metals down to 0.079 MUM Cu(2+), 0.025 MUM Hg(2+),
      0.024 MUM Pb(2+) and 0.044 MUM Cd(2+). Furthermore, good linear concentration
      ranges were achieved for Cu(2+) (0.079-16 MUM), Hg(2+) (0.025-5 MUM), Pb(2+)
      (0.10-15 MUM) and Cd(2+) (0.04-62 MUM). The analysis of the nature of the
      inhibition of glucose oxidase in the PPy-GOx biosensor by these metals was
      achieved by Dixon and Cornish-Bowden plots. The shapes of the curves (exponential
      decay, parabolic and linear) obtained for the inhibitors suggest that the
      inhibition by the metal ions may not be exclusively directed at the essential -SH
      group, but involve additional binding sites of the enzyme. Dixon and Cornish
      Bowden plots suggest that the inhibition is competitive for Cd(2+), while non
      competitive inhibition was observed for other metal ions. The ultra-thin PPy-GOx
      film enabled improved permeability to the metal inhibitors than possible with
      conventional biosensors with thicker films and, hence, better reflects the actual
      inhibition effect of the trace metals on the enzyme activity. The use of the
      ultra-thin film also eliminated the usual need for incubation of the enzyme
      electrode for a long period in the presence of the inhibitors. Furthermore, a
      rapid recovery of the enzyme activity was achieved by simply washing the
      electrode with water and storing in phosphate buffer for 10-15 min. The proposed
      biosensing approach was successfully used for the detection of individual trace
      metals in tap water, achieving a 98-101% recovery.

PMID- 25770608
TI  - Determination of VOSCs in sewer headspace air using TD-GC-SCD.
AB  - The management of odorous emissions from sewer networks has become an important
      issue for sewer operators resulting in the need to better understand the
      composition of volatile organic sulfur compounds (VOSCs). In order to
      characterise the composition of such malodorous emissions, a method based on
      thermal desorption (TD) and gas chromatography coupled to sulfur
      chemiluminescence detector (GC-SCD) has been developed to determine a broader
      range of VOSCs, hydrogen sulfide (H2S), methanethiol (MeSH), ethanethiol (EtSH),
      dimethyl sulfide (DMS), carbon disulfide (CS2), ethylmethyl sulfide (EMS), 1
      butanethiol (1-BuSH), dimethyl disulfide (DMDS), diethyl disulfide (DEDS), and
      dimethyl trisulfide (DMTS). Parameters affecting the chromatographic behaviour of
      the target compounds were studied (e.g., temperature program, carrier gas
      velocity) as well as the experimental conditions affecting the
      adsorption/desorption process (temperature, flow and time). Optimised extraction
      of VOSCs samples was achieved under adsorption temperatures of less than -20
      degrees C, and a desorption flow rate of ~6 ml/min. Active collection on the cold
      trap enabled a small gas volume of 50-100ml to be sampled for all analytes
      without breakthrough. Calibration curves were derived at different TD loading
      volumes with determined linearity ranging between 0.09 ng and 60.1 ng. The method
      detection limits (MDLs) were in the range of 0.10-5.26 MUg/m(3) with TD
      recoveries higher than 66% and reproducibility (relative standard deviation
      values) between 1.8% and 6.1% being obtained for all compounds. The VOSCs
      characterisation at different sewerage collection sites in Sydney, Australia (for
      seasonal, weekly and diurnal) showed that six of the ten targeted compounds were
      consistently detected at all sample events. Diurnal patterns of VOSCs
      investigated were clearly observed with the highest concentration occurring after
      12 pm (noon) for H2S and MeSH. The consecutive 5 day analysis showed no
      significant difference in the targeted VOSCs concentrations and demonstrated the
      suitability of the method for routine sewer VOSCs emission measurements.

PMID- 25770609
TI  - Simple and label-free detection of DNA hybridization on a modified graphene
      nanosheets electrode.
AB  - In this study, an effective method was devised to synthesize amelogenin genes in
      solution and to amplify electrical detection of DNA hybridization based on
      graphene nanosheets (GNs) modified glassy carbon electrode (GCE). GNs are well
      known as effective biocompatible and conductive materials that can provide large
      surface area and a sufficient numbers of binding points for DNA immobilization.
      The biosensor fabrication processes and the electrochemical responses of probe
      immobilization and hybridization with target DNA were investigated by
      electrochemical impedance spectroscopy (EIS) and cyclic voltammetry (CV) using
      [Fe(CN)6](3-/4-) as an electrochemical redox. Due to minimum nonspecific DNA
      adsorption, a very high specificity of DNA hybridization was achieved, and the
      hybridization rate of the target DNA in optimum conditions was increased
      significantly. With this approach, the target DNA could be quantified in a linear
      range from 1.0*10(-20) to 1.0*10(-14) mol L(-1) for the first segment and from
      1.0*10(-13) to 1.0*10(-6) mol L(-1) for the second segment, with a detection
      limit of 7.1*10(-21) mol L(-1) by 3s(b). In addition, the biosensor exhibited a
      high level of stability and repeatability, even for the determination of DNA
      sequences in real samples without amplification.

PMID- 25770610
TI  - A high performance nonenzymatic electrochemical glucose sensor based on
      polyvinylpyrrolidone-graphene nanosheets-nickel nanoparticles-chitosan
      nanocomposite.
AB  - In this report, a new nanocomposite was successfully synthesized by chemical
      deposition of nickel nanoparticles (NiNPs) on polyvinylpyrrolidone (PVP)
      stabilized graphene nanosheets (GNs) with chitosan (CS) as the protective
      coating. The as obtained nanocomposite (PVP-GNs-NiNPs-CS) was characterized by X
      ray photoelectron spectroscopy (XPS) and transmission electron microscopy (TEM).
      Benefiting from the synergistic effect of GNs (large surface area and high
      conductivity), NiNPs (high electrocatalytic activity towards the glucose
      oxidation) and CS (good film-forming and antifouling ability), a nonenzymatic
      electrochemical glucose sensor was established. The nanocomposite displays
      greatly enhanced electrocatalytic activity towards the glucose oxidation in NaOH
      solution. The PVP-GNs-NiNPs-CS based electrochemical glucose sensor demonstrates
      good sensitivity, wide linear range (0.1 MUM-0.5 mM), outstanding detection limit
      (30 nM), attractive selectivity, good reproducibility, high stability as well as
      prominent feasibility for the real sample analysis. The proposed experiment might
      open up a new possibility for widespread use of non-enzymatic sensors for
      monitoring blood glucose owing to its advantages of low cost, simple preparation
      and excellent properties for glucose detection.

PMID- 25770611
TI  - Biosensor based on inhibition of monoamine oxidases A and B for detection of beta
      carbolines.
AB  - beta-Carbolines are inhibitors of monoamine oxidases (MAO-A and MAO-B) and can be
      found in foods, hallucinogenic plant or various drugs. We have developed a fast
      analysis method for beta-carbolines based on the inhibition of MAO. The enzymes
      were immobilized on screen-printed electrodes modified with a stabilized film of
      Prussian blue that contain also copper. We have used benzylamine as substrate for
      the enzymatic reaction and the hydrogen peroxide was measured amperometrically at
      -50 mV. The detection limits obtained were 5.0 uM for harmane and 2.5 uM for both
      harmaline and norharmane. The MAO-A is inhibited by all three tested beta
      carbolines (harmane, norharmane, and harmaline) while MAO-B is inhibited only by
      norharmane. The presence of norharmane in mixtures of beta-carbolines can be
      identified based on the difference between the cumulative inhibition of MAO-A by
      all beta-carbolines and MAO-B inhibition. The developed biosensors were used for
      food analysis.

PMID- 25770612
TI  - Non-invasive quantitative micro-PIXE-RBS/EBS/EBS imaging reveals the lost
      polychromy and gilding of the Neo-Assyrian ivories from the Louvre collection.
AB  - Antique objects are known to have been brightly colored. However, the appearance
      of these objects has changed over time and paint traces are rarely preserved. The
      surface of ivory objects (8th century B.C., Syria) from the Louvre museum
      collection (Paris) have been non-invasively studied by simultaneous particle
      induced X-ray emission (PIXE) and Rutherford and elastic backscattering
      spectrometry (RBS/EBS) micro-imaging at the AGLAE facility (C2RMF, Paris).
      Qualitative 2D chemical images of elements ranging from Na to Pb on the surface
      of the ancient ivory carvings provide evidence of lost polychromy and gilding.
      Quantitative PIXE data of specific areas allow discrimination between traces of
      sediments and former polychromy. Different shades of blue can be differentiated
      from particular Pb/Cu ratios. The characterization of gilding based on RBS data
      demonstrates the exceptional technological skills of the Phoenician craftsmen
      supposed to have carved the Arslan Tash ivories. More precise reconstructions of
      the original polychromy compared to previous studies and a criterion for the
      authentication of ancient gilded ivory object are proposed. 

PMID- 25770614
TI  - Accurate determination of selected pesticides in soya beans by liquid
      chromatography coupled to isotope dilution mass spectrometry.
AB  - A sensitive, accurate and simple liquid chromatography coupled with mass
      spectrometry method for the determination of 10 selected pesticides in soya beans
      has been developed and validated. The method is intended for use during the
      characterization of selected pesticides in a reference material. In this process,
      high accuracy and appropriate uncertainty levels associated to the analytical
      measurements are of utmost importance. The analytical procedure is based on
      sample extraction by the use of a modified QuEChERS (quick, easy, cheap,
      effective, rugged, safe) extraction and subsequent clean-up of the extract with
      C18, PSA and Florisil. Analytes were separated on a C18 column using gradient
      elution with water-methanol/2.5 mM ammonium acetate mobile phase, and finally
      identified and quantified by triple quadrupole mass spectrometry in the multiple
      reaction monitoring mode (MRM). Reliable and accurate quantification of the
      analytes was achieved by means of stable isotope-labelled analogues employed as
      internal standards (IS) and calibration with pure substance solutions containing
      both, the isotopically labelled and native compounds. Exceptions were made for
      thiodicarb and malaoxon where the isotopically labelled congeners were not
      commercially available at the time of analysis. For the quantification of those
      compounds methomyl-(13)C2(15)N and malathion-D10 were used respectively. The
      method was validated according to the general principles covered by DG SANCO
      guidelines. However, validation criteria were set more stringently. Mean
      recoveries were in the range of 86-103% with RSDs lower than 8.1%. Repeatability
      and intermediate precision were in the range of 3.9-7.6% and 1.9-8.7%
      respectively. LODs were theoretically estimated and experimentally confirmed to
      be in the range 0.001-0.005 mg kg(-1) in the matrix, while LOQs established as
      the lowest spiking mass fractionation level were in the range 0.01-0.05 mg kg(
      1). The method reliably identifies and quantifies the selected pesticides in soya
      beans at appropriate uncertainty levels, making it suitable for the
      characterization of candidate reference materials.

PMID- 25770613
TI  - Determination of N-nitrosodiethanolamine, NDELA in cosmetic ingredients and
      products by mixed mode solid phase extraction and UPLC-tandem mass spectrometry
      with porous graphitic carbon column through systemic sample pre-cleanup
      procedure.
AB  - A rapid, sensitive, accurate and specific ultra-performance liquid chromatography
      coupled to tandem mass spectrometry (UPLC-MS/MS) method for the detection of N
      nitrosodiethanolamine (NDELA), a highly toxic contaminant in cosmetic raw
      materials and products was developed and validated. Systematized sample
      preparation steps were developed according to product types. Various SPE
      cartridges and columns were examined to establish the condition of SPE and
      chromatographic separation for NDELA. Sample cleanup steps consisting of solvent
      and liquid-liquid extraction tailored to the various sample matrix types were
      established prior to mixed mode SPE (Bond Elut AccuCAT). Chromatographic
      separation was achieved within 7 min on a porous graphitic carbon (PGC) column
      using a gradient elution with the mobile phase of 1mM ammonium acetate containing
      0.1% acetic acid and methanol. NDELA was monitored using an electrospray positive
      ionization mass spectrometry in the multiple reaction monitoring (MRM) mode (m/z
      134.9>103.7(quantifier) and 73.7(qualifier ion)) with d8-NDELA (m/z 143.1>111.0)
      as internal standard. The standard curves were linear over the concentration
      range of 1-100 ng/mL with a correlation coefficient higher than 0.99. The limit
      of detection (LOD) and the limit of quantification (LOQ) was 10 and 20 MUg/kg,
      respectively (0.5 and 1 ng/mL in standard solution). The intra- and inter-day
      precisions were estimated to be below 11.1% and accuracies were within the range
      of 90.8-115.8%. The validated method was successfully applied to the analysis of
      real samples including raw materials, skin care, make-up, shampoos and hair
      products.

PMID- 25770615
TI  - Simultaneous determination of mosapride and its active des-p-fluorobenzyl and 4'
      N-oxide metabolites in rat plasma using UPLC-MS/MS: an application for a
      pharmacokinetic study.
AB  - An efficient and sensitive ultra-performance chromatography-tandem mass
      spectrometry method to simultaneously determinate and quantify mosapride (M) and
      its des-p-fluorobenzyl (M1) and 4'-N-oxide (M2) metabolites using carbamazepine
      as the internal standard (IS) in rat plasma has been developed and validated.
      Analytes were extracted from aliquots of plasma with ethyl acetate after
      alkalization using saturated sodium carbonate solution. The chromatographic
      separation was conducted on a BEH C18 column (100 mm * 2.1 mm, 1.7 MUm) with the
      gradient elution using a mobile phase of acetonitrile - 0.2% formic acid in water
      at a flow rate of 0.25 mL/min for 4 min. The tandem mass spectrometric detection
      was conducted using multiple reaction monitoring (MRM) by the positive
      electrospray ionization (ESI). The ion transitions monitored were m/z 422->198
      for mosapride, m/z 314->198 for M1, m/z 438->109 for M2 and m/z 237->194 for IS.
      The linear ranges of the calibration curves were 1.0-2000 ng/mL for M, 0.75-1875
      ng/mL for M1 and 0.4-40 ng/mL for M2. And the corresponding lower limits of
      quantitation (LLOQ) of the method were 1.0, 0.75, 0.4 ng/mL for M, M1 and M2,
      respectively. The intra- and inter-day precision for all analytes were less than
      8.1% and 11.6%, respectively. The inter-assay mean accuracy was between -6.4% and
      8.1%. No relevant cross-talk and matrix effect were observed. There were
      significant differences between male and female rats for M, M1 and M2.

PMID- 25770616
TI  - Post-synthetic modification of MIL-101(Cr) with pyridine for high-performance
      liquid chromatographic separation of tocopherols.
AB  - Effective separation of tocopherols is challenging and significant due to their
      structural similarity and important biological role. Here we report the post
      synthetic modification of metal-organic framework (MOF) MIL-101(Cr) with pyridine
      for high-performance liquid chromatographic (HPLC) separation of tocopherols.
      Baseline separation of four tocopherols was achieved on a pyridine-grafted MIL
      101(Cr) packed column within 10 min using hexane/isopropanol (96:4, v/v) as the
      mobile phase at a flow rate of 0.5 mL min(-1). The pyridine-grafted MIL-101(Cr)
      packed column gave high column efficiency (85,000 plates m(-1) for delta
      tocopherol) and good precision (0.2-0.3% for retention time, 1.8-3.4% for peak
      area, 2.6-2.7% for peak height), and also offered much better performance than
      unmodified MIL-101(Cr) and commercial amino-bonded silica packed column for HPLC
      separation of tocopherols. The results not only show the promising application of
      pyridine-grafted MIL-101(Cr) as a novel stationary phase for HPLC separation of
      tocopherols, but also reveal a facile post-modification of MOFs to expand the
      application of MOFs in separation sciences.

PMID- 25770617
TI  - Inverse Abbe-method for observing small refractive index changes in liquids.
AB  - This study concerns an optical method for the detection of minuscule refractive
      index changes in the liquid phase. The proposed method reverses the operation of
      the traditional Abbe refractometer and thus utilizes the light dispersion
      properties of materials, i.e. it involves the dependence of the refractive index
      on light wavelength. In practice, the method includes the detection of light
      reflection spectra in the visible spectral range. This inverse Abbe method is
      suitable for liquid quality studies e.g. for monitoring water purity. Tests have
      shown that the method reveals less than per mil NaCl or ethanol concentrations in
      water. 

PMID- 25770618
TI  - Coupling of non-selective adsorption with selective elution for novel in-line
      separation and detection of cadmium by vapour generation atomic absorption
      spectrometry.
AB  - Non-selective adsorption of Cd(2+) ions on a cation exchange fiber and subsequent
      selective elution with a KI solution has been strategically utilized to develop a
      highly selective in-line separation of Cd(2+) ions from other metal ions for its
      rapid and reliable quantification by cold vapour-atomic absorption spectrometry.
      After retention of Cd(2+) with a high efficiency on cation exchange fiber,
      selective elution of the retained Cd(2+) was subsequently accomplished with 0.3M
      KI. Vapour generation of Cd for in-line CV-AAS determination was then achieved by
      merging the eluate with HCl and NaBH4. Interferences from most base metals with
      the vapour generation of Cd were eliminated by this approach, with the exception
      of Pb(2+)ions which was removed by co-precipitation with BaSO4 prior to the in
      line separation. Substantial improvement in sensitivity of the in-line CV-AAS
      determination of Cd was achieved by increasing the sample loading time. A
      detection limit of 0.6 ng L(-1) (3sigma) was obtained with sample loading time of
      120 s, corresponding to a consumption of 24 mL of sample solution. Application of
      the method to the determination of Cd in certified sediment and fish samples gave
      a good agreement with the certified values. Further validation by recovery study
      in real fish sample digests and water gave average Cd recoveries of 98.7+/-1.0%
      for fish and 92+/-3% for water with RSD of 1.5% for fish and 4% for water,
      respectively.

PMID- 25770619
TI  - Real-time fluorescence assays of alkaline phosphatase and ATP sulfurylase
      activities based on a novel PPi fluorescent probe.
AB  - An anthracene-armed tetraaza macrocyclic fluorescent probe 3-(9-anthrylmethyl)
      3,6,9,15-tetraazabicyclo[9.3.1]pentadeca-1(15),11,13-triene(l) for detecting
      Zn(2+) in aqueous medium was synthesized. L-Zn(2+) complex, showed selectivity
      toward pyrophosphate ion (PPi) by quenching the fluorescence in aqueous HEPES
      buffer (pH 7.4). Furthermore, L-Zn(2+) was also used to set up a real-time
      fluorescence assay for monitoring enzyme activities of alkaline phosphatase (ALP)
      and adenosine triphosphate sulfurylase (ATPS). In the presence of ALP inhibitor
      Na3VO4 and ATPS inhibitor chlorate, two enzymes activities decreased obviously,
      respectively. 

PMID- 25770620
TI  - On plate graphite supported sample processing for simultaneous lipid and protein
      identification by matrix assisted laser desorption ionization mass spectrometry.
AB  - The simultaneous identification of lipids and proteins by matrix assisted laser
      desorption ionization-mass spectrometry (MALDI-MS) after direct on-plate
      processing of micro-samples supported on colloidal graphite is demonstrated.
      Taking advantages of large surface area and thermal conductivity, graphite
      provided an ideal substrate for on-plate proteolysis and lipid extraction. Indeed
      proteins could be efficiently digested on-plate within 15 min, providing sequence
      coverages comparable to those obtained by conventional in-solution overnight
      digestion. Interestingly, detection of hydrophilic phosphorylated peptides could
      be easily achieved without any further enrichment step. Furthermore, lipids could
      be simultaneously extracted/identified without any additional
      treatment/processing step as demonstrated for model complex samples such as milk
      and egg. The present approach is simple, efficient, of large applicability and
      offers great promise for protein and lipid identification in very small samples.

PMID- 25770621
TI  - Chemometric assisted ultrasound leaching-solid phase extraction followed by
      dispersive-solidification liquid-liquid microextraction for determination of
      organophosphorus pesticides in soil samples.
AB  - Ultrasound leaching-solid phase extraction (USL-SPE) followed by dispersive
      solidification liquid-liquid microextraction (DSLLME) was developed for
      preconcentration and determination of organophosphorus pesticides (OPPs) in soil
      samples prior gas chromatography-mass spectrometry analysis. At first, OPPs were
      ultrasonically leached from soil samples by using methanol. After centrifugation,
      the separated methanol was diluted to 50 mL with double-distillated water and
      passed through the C18 SPE cartridge. OPPs were eluted with 1 mL acetonitrile.
      Thus, 1 mL acetonitrile extract (disperser solvent) and 10 uL 1-undecanol
      (extraction solvent) were added to 5 mL double-distilled water and a DSLLME
      technique was applied. The variables of interest in the USL-SPE-DSLLME method
      were optimized with the aid of chemometric approaches. First, in screening
      experiments, fractional factorial design (FFD) was used for selecting the
      variables which significantly affected the extraction procedure. Afterwards, the
      significant variables were optimized using response surface methodology (RSM)
      based on central composite design (CCD). Under the optimum conditions, the
      enrichment factors were 6890-8830. The linear range was 0.025-625 ng g(-1) and
      limits of detection (LODs) were between 0.012 and 0.2 ng g(-1). The relative
      standard deviations (RSDs) were in the range of 4.06-8.9% (n=6). The relative
      recoveries of OPPs from different soil samples were 85-98%.

PMID- 25770622
TI  - Prediction of HPLC retention times of tebipenem pivoxyl and its degradation
      products in solid state by applying adaptive artificial neural network with
      recursive features elimination.
AB  - A sensitive and fast HPLC method using ultraviolet diode-array detector
      (DAD)/electrospray ionization tandem mass spectrometry (Q-TOF-MS/MS) was
      developed for the determination of tebipenem pivoxyl and in the presence of
      degradation products formed during thermolysis. The chromatographic separations
      were performed on stationary phases produced in core-shell technology with
      particle diameter of 5.0 um. The mobile phases consisted of formic acid (0.1%)
      and acetonitrile at different ratios. The flow rate was 0.8 mL/min while the
      wavelength was set at 331 nm. The stability characteristics of tebipenem pivoxyl
      were studied by performing stress tests in the solid state in dry air (RH=0%) and
      at an increased relative air humidity (RH=90%). The validation parameters such as
      selectivity, accuracy, precision and sensitivity were found to be satisfying. The
      satisfied selectivity and precision of determination were obtained for the
      separation of tebipenem pivoxyl from its degradation products using a stationary
      phase with 5.0 um particles. The evaluation of the chemical structure of the 9
      degradation products of tebipenem pivoxyl was conducted following separation
      based on the stationary phase with a 5.0 um particle size by applying a Q-TOF
      MS/MS detector. The main degradation products of tebipenem pivoxyl were
      identified: a product resulting from the condensation of the substituents of 1
      (4,5-dihydro-1,3-thiazol-2-yl)-3-azetidinyl]sulfanyl and acid and ester forms of
      tebipenem with an open beta-lactam ring in dry air at an increased temperature
      (RH=0%, T=393 K) as well as acid and ester forms of tebipenem with an open beta
      lactam ring at an increased relative air humidity and an elevated temperature
      (RH=90%, T=333 K). Retention times of tebipenem pivoxyl and its degradation
      products were used as training data set for predictive model of quantitative
      structure-retention relationship. An artificial neural network with adaptation
      protocol and extensive feature selection process was created. Input parameters
      for model were calculated from molecular geometries optimized with application of
      Density Functional Theory. The model was prepared and optimized especially for
      small data sets such as degradation products of specific compound. Validation of
      the model with statistical test against requirements for QSAR showed its ability
      for prediction of retention times within given data set. Mean error of 24.75%
      (0.8 min) was achieved with utilization of topological, geometrical and
      electronic descriptors.

PMID- 25770623
TI  - Elemental analysis of materials in an underwater archeological shipwreck using a
      novel remote laser-induced breakdown spectroscopy system.
AB  - LIBS analysis of submerged materials in an underwater archeological site has been
      performed for the first time. A fiber-optics-based remote instrument was designed
      for the recognition and identification of archeological assets in the wreck of
      the Bucentaure (Bay of Cadiz, South of Spain). The LIBS prototype featured both
      single-pulse (SP-LIBS) and multi-pulse excitation (MP-LIBS). The use of multi
      pulse excitation allowed an increased laser beam energy (up to 95 mJ) transmitted
      through the optical fiber. This excitation mode results in an improved
      performance of the equipment in terms of extended range of analysis (to a depth
      of 50 m) and a broader variety of samples to be analyzed (i.e., rocks, marble,
      ceramics and concrete). Compared to single-pulse, an intensity enhancement factor
      of 15* was observed at the same irradiance value, 1.89 GW/cm(2). Thus, a longer
      pulse duration promotes the heating and melting of the sample, resulting in a
      greater mass ablated. As a consequence of the optimization of experimental
      conditions performed in laboratory, underwater characterization of ancient
      pottery was achieved.

PMID- 25770624
TI  - Detection of dopamine on a mercapto-terminated hexanuclear Fe(III) cluster
      modified gold electrode.
AB  - In this study, a novel mercapto-terminated hexanuclear iron(III) cluster
      [Fe6O2(OH)2(O2CC6H4SCH3)10(hep)2].CH3CN.CH2Cl2 [hep=2-(2-hydroxyethyl) pyridine]
      (Fe6) modified Au electrode was fabricated, having highly sensitive dopamine (DA)
      detection capabilities. In such Fe6 molecules, 10 thiomethyl groups are located
      at the periphery of the cluster, which enable the Fe6 molecules to self-assemble
      onto the surface of Au electrodes through the formation of Au-S bonds. The as
      prepared Fe6-modified Au electrode (Au/Fe6) exhibits excellent electrocatalytic
      activity for the oxidation of dopamine (DA) in PBS with a diffusion coefficient
      of 3.12*10(-5) cm(2)/s. Using the square wave voltammetry (SWV) technique, the
      calibration curve for DA determination was obtained in the range of 0.2 to 30
      MUM, and the detection limit for DA was ~0.07 MUM. Furthermore, the modified
      electrode can accurately separate the DA signal from the interfering effect of
      uric acid (UA), thus providing simultaneous detection of DA and UA in their
      binary mixtures. This electrode can be reliably used to assay DA in its real drug
      composition.

PMID- 25770625
TI  - A tunable isoelectric focusing via moving reaction boundary for two-dimensional
      gel electrophoresis and proteomics.
AB  - Routine native immobilized pH gradient isoelectric focusing (IPG-IEF) and two
      dimensional gel electrophoresis (2DE) are still suffering from unfortunate
      reproducibility, poor resolution (caused by protein precipitation) and
      instability in characterization of intact protein isoforms and posttranslational
      modifications. Based on the concept of moving reaction boundary (MRB), we firstly
      proposed a tunable non-IPG-IEF system to address these issues. By choosing proper
      pairs of catholyte and anolyte, we could achieve desired cathodic and anodic
      migrating pH gradients in non-IPG-IEF system, effectively eliminating protein
      precipitation and uncertainty of quantitation existing in routine IEF and 2DE,
      and enhancing the resolution and sensitivity of IEF. Then, an adjustable 2DE
      system was developed by combining non-IPG-IEF with polyacrylamide gel
      electrophoresis (PAGE). The improved 2DE was evaluated by testing model proteins
      and colon cancer cell lysates. The experiments revealed that (i) a tunable pH
      gradient could be designed via MRB; (ii) up to 1.65 fold improvement of
      resolution was achieved via non-IPG-IEF; (iii) the sensitivity of developed
      techniques was increased up to 2.7 folds; and (iv) up to about 16.4% more protein
      spots could be observed via the adjustable 2DE as compared with routine one. The
      developed techniques might contribute to complex proteome research, especially
      for screening of biological marker and analysis of extreme acidic/alkaline
      proteins. 

PMID- 25770626
TI  - Ag-doped ZnO nanoellipsoids: potential scaffold for photocatalytic and sensing
      applications.
AB  - Well-crystalline Ag-doped ZnO nanoellipsoids (NEs) were synthesized in large
      quantity and used as effective photocatalyst for the photocatalytic degradation
      of methyl orange (MO) and efficient electron mediator for the fabrication of
      highly sensitive, reliable and robust hydrazine chemical sensor. The Ag-doped NEs
      were synthesized by facile low-temperature (~60 degrees C) solution process and
      characterized in detail using various characterization techniques. The
      characterizations revealed that the synthesized nanostructures are well
      crystalline, possessing ellipsoidal shapes and were grown in very high density.
      The photocatalytic activities of these Ag-doped NEs were evaluated by measuring
      the rate of photodegradation reaction of hazardous methyl orange (MO) dye under
      UV light irradiation. By comparing the photocatalytic performance of Ag-doped ZnO
      NEs with those of ZnO nanoflowers, the former was found to be a much superior
      photocatalyst than the later. Further, Ag-doped ZnO NEs based hydrazine sensor
      exhibited a high sensitivity of ~9.46 uA/cm(2)uM and detection limit of 0.07 uM
      in a response time of <10s. Thus we find that Ag-doped ZnO nanomaterials
      synthesized by simple solution process holds potential as efficient
      photocatalysts and efficient electron mediators for the fabrication of robust and
      highly sensitive chemical sensors.

PMID- 25770627
TI  - Microfluidic derivatisation technique for determination of gaseous molecular
      iodine with GC-MS.
AB  - Gaseous molecular iodine (I2) is an important source of reactive iodine in the
      marine atmosphere, but the sources of I2 are not well understood due to the lack
      of an easily accessible, sensitive and robust technique for analysis. In this
      study a microfluidic derivatisation technique combined with GC-MS has been
      developed to measure gaseous I2. Good linearity in the range of 0.2-416 ppb and
      low detection limits varying from 6 to 25 ppt for different derivatisation
      reagents have been achieved, which is a substantial improvement in sensitivity
      compared with the spectrophotometric method (detection limit of 1.20 ppb) in our
      previous study [L.J. Carpenter, S.M. MacDonald, M.D. Shaw, R. Kumar, R.W.
      Saunders, R. Parthipan, J. Wilson, J.M.C. Plane, Nature Geoscience, 6 (2013) 108
      111]. The microfluidic technique was employed to quantify I2 produced from the
      heterogeneous reactions of potassium iodide solution and ozone. Good agreement
      was observed between the results of the microfluidic technique and the simulation
      of a coupled surface water-air kinetic model in the amount of I2 produced on the
      ozonolysis of iodide solutions.

PMID- 25770628
TI  - Esophageal Carcinoma: Current Concepts in the Role of Imaging in Staging and
      Management.
AB  - Over the past few decades, the survival of esophageal cancer patients has
      improved owing to early detection and advances in multimodality treatment
      strategies. Imaging plays an important role in every step in the management of
      esophageal cancer, including diagnosis, staging, assessment of treatment
      response, and post-treatment surveillance. In this article, we provide a
      comprehensive review of the role of imaging in these various time points of
      esophageal cancer management. 

PMID- 25770629
TI  - Review of Thoracic Imaging Findings Unique to Women.
AB  - PURPOSE: Traditionally, indications for imaging studies of women are considered
      to be related to screening for and evaluation of disease of the female breast and
      pelvis. However, a number of chest diseases and associated intrathoracic imaging
      findings are unique to women and should be recognized by general radiologists, as
      well as chest and women-imaging specialists. CONCLUSIONS: The sex-specific
      findings unique to women include normal anatomical variants, primary lung
      disease, complications of breast and gynaecological disease, and pregnancy
      related conditions. Classification, description, and illustration of gender
      specific chest imaging findings are the objective of this article.

PMID- 25770630
TI  - Marx on radiology's future.

PMID- 25770631
TI  - Pulmonary Vessel Cross-sectional Area before and after Liver Transplantation:
      Quantification with Computed Tomography.
AB  - RATIONALE AND OBJECTIVES: Pulmonary vascular complications of liver disease have
      a substantial impact on morbidity and mortality in patients who undergo liver
      transplant. The effect of liver transplantation on the pulmonary vasculature in
      patients without pulmonary vascular disease, however, has not been described.
      This study was undertaken to characterize the regional effect of liver transplant
      on the cross-sectional area (CSA) of pulmonary vessels. MATERIALS AND METHODS: We
      performed a single-center, retrospective, cohort study of patients who had a
      liver transplant between 2002 and 2012 and who had chest computed tomography
      scans within 1 year before and after transplant. Using ImageJ software, we
      measured the CSA of small pulmonary vessels (0-5 mm(2)) and the total lung CSA to
      calculate the percent CSA of pulmonary vessels <5 mm (%CSA<5) at the level of the
      aortic arch, carina, and right inferior pulmonary vein (RIPV). Pretransplant and
      posttransplant, %CSA<5 were compared, and associations of pretransplant %CSA<5
      with clinical parameters were measured. RESULTS: There was a significant decrease
      in %CSA<5 at the level of the RIPV (0.19% [interquartile range {IQR}, 0.15-0.26]
      before vs. 0.15% [IQR, 0.12-0.21] after; P = .0003), with a median change of 
      16.2% (IQR, -39.3 to 3.9) posttransplant. Changes at the level of the aortic arch
      and carina were not significant. Pretransplant RIPV %CSA<5 was not significantly
      correlated with severity of liver disease or oxygenation but was inversely
      correlated with percent change in %CSA<5 (r = -0.39; P = .0039). CONCLUSIONS:
      This is the first study to describe a significant regional change in the
      pulmonary vessels of patients without known pulmonary vascular disease who
      undergo liver transplant.

PMID- 25770632
TI  - Dual-Source Dual-Energy CT Angiography of the Supra-Aortic Arteries with Tin
      Filter: Impact of Tube Voltage Selection.
AB  - RATIONALE AND OBJECTIVES: Automatic bone and plaque subtraction (BPS) in computed
      tomographic angiographic (CTA) examinations using dual-energy CT (DECT) remains
      challenging because of beam-hardening artifacts in the shoulder region and close
      proximity of the internal carotid artery to the base of the skull. The selection
      of the tube voltage combination in dual-source CT influences the spectral
      separation and the susceptibility for artifacts. The purpose of this study was to
      assess which tube voltage combination leads to an optimal image quality of head
      and neck DECT angiograms after bone subtraction. MATERIALS AND METHODS: Fifty-one
      patients received tin-filter-enhanced DECT angiograms of the supra-aortic
      arteries using two voltage protocols: 24 patients were studied using 80/Sn140 kV
      and 27 using a 100/Sn140 kV protocol, both protocols with an additional tin
      filter. A commercially available DE-CTA BPS algorithm was used. Artificial vessel
      erosions in BPS maximum intensity projections (four-level Likert scale with CTA
      source data as reference) and vessel signal-to-noise ratio (SNR) were assessed in
      the level of the shoulders and the base of the skull in each patient and
      compared. RESULTS: At the level of the shoulder, 100/Sn140 kV achieved higher SNR
      (23.4 +/- 6.4 at 80/Sn140 kV vs. 35.1 +/- 11.8 at 100/Sn140 kV; P < .0001) with
      less erosions (erosion score 3.9 +/- 0.4 in 80/Sn140 kV vs. 2.1 +/- 1.3 in
      100/Sn140 kV; P < .0001) than 80/Sn140 kV. At the level of the skull base,
      erosion scores and objective image quality of arterial segments were comparable
      with both protocols (P = .14). CONCLUSIONS: The 100/Sn140 kV protocol achieved
      more favorable results for BPS of the supra-aortic arteries than the 80/Sn140 kV
      protocol.

PMID- 25770634
TI  - Diagnosis and endovascular treatment of "vaculitides". Introduction.

PMID- 25770633
TI  - Automated tumor volumetry using computer-aided image segmentation.
AB  - RATIONALE AND OBJECTIVES: Accurate segmentation of brain tumors, and
      quantification of tumor volume, is important for diagnosis, monitoring, and
      planning therapeutic intervention. Manual segmentation is not widely used because
      of time constraints. Previous efforts have mainly produced methods that are
      tailored to a particular type of tumor or acquisition protocol and have mostly
      failed to produce a method that functions on different tumor types and is robust
      to changes in scanning parameters, resolution, and image quality, thereby
      limiting their clinical value. Herein, we present a semiautomatic method for
      tumor segmentation that is fast, accurate, and robust to a wide variation in
      image quality and resolution. MATERIALS AND METHODS: A semiautomatic segmentation
      method based on the geodesic distance transform was developed and validated by
      using it to segment 54 brain tumors. Glioblastomas, meningiomas, and brain
      metastases were segmented. Qualitative validation was based on physician ratings
      provided by three clinical experts. Quantitative validation was based on
      comparing semiautomatic and manual segmentations. RESULTS: Tumor segmentations
      obtained using manual and automatic methods were compared quantitatively using
      the Dice measure of overlap. Subjective evaluation was performed by having human
      experts rate the computerized segmentations on a 0-5 rating scale where 5
      indicated perfect segmentation. CONCLUSIONS: The proposed method addresses a
      significant, unmet need in the field of neuro-oncology. Specifically, this method
      enables clinicians to obtain accurate and reproducible tumor volumes without the
      need for manual segmentation.

PMID- 25770635
TI  - Diagnostic approach in patients with suspected vasculitis.
AB  - Vasculitides are a heterogeneous group of disorders that share the common feature
      of inflammation of the blood vessel wall. Vasculitis can be a systemic or
      localized process and depending on the disorder can affect large, medium, or
      small vessels. Vascular physicians including interventional radiologists often
      may be involved early in these cases before the establishment of a diagnosis as
      these patients may present with manifestations attributable to occlusive vascular
      syndromes. In this article, we discuss the presenting signs and symptoms of
      patients with vasculitis as well as laboratory and imaging studies required to
      further evaluate these disorders and treatment options, which include
      interventional as well as noninterventional options. 

PMID- 25770636
TI  - Buerger disease (thromboangiitis obliterans).
AB  - Buerger disease is a nonatherosclerotic vasculitis that is triggered by
      substantial exposure to tobacco. This disease usually affects small- and medium
      sized arteries in the upper and lower extremities. All clinicians who take care
      of patients with peripheral arterial disease should know the clinical features
      and diagnostic evaluation of Buerger disease. In this article, we review the
      clinical presentation and diagnostic criteria for Buerger disease. We describe
      the diagnostic work-up of patients suspected of having Buerger disease and
      discuss the typical findings on noninvasive arterial studies and angiography.
      Lastly, we review the management of these patients, including medical therapy,
      with an emphasis on smoking cessation, as well as the potential role of
      revascularization, both surgical and endovascular. 

PMID- 25770637
TI  - Raynaud syndrome.
AB  - Raynaud syndrome (RS) was first described by the French physician Maurice Raynaud
      in 1862 with the characteristic tricolor change featuring pallor (ischemic
      phase), cyanosis (deoxygenation phase), and erythema (reperfusion phase) induced
      by cold or stress. Although the underlying pathophysiological mechanism is
      unclear, alterations in activity of the peripheral adrenoceptor have been
      implicated, specifically an enhanced smooth muscle contraction due to
      overexpression or hyperactivity of postsynaptic alpha 2 receptors. There are 2
      ways that RS can appear clinically; isolated, formerly referred as Raynaud
      disease or now primary RS and in association with other conditions, usually
      connective tissue disorders (eg, Sjogren syndrome, systemic lupus erythematosus,
      scleroderma, and rheumatoid arthritis), frequently called Raynaud phenomenon or
      secondary RS. The estimated prevalence in the general population is 3%-5%, with a
      higher prevalence in women than in men. The diagnosis is mainly clinical, based
      on patient descriptions of skin changes. Upper extremity pulse-volume recording
      is used to rule out proximal arterial obstruction. The differentiation between a
      vasospastic vs and obstructive mechanism is made using digital pressures and
      photoplethysmography, where an obstructive mechanism has decreased pressures and
      blunted waveforms. Cold challenge testing, such as ice water immersion with
      temperature recovery, is highly sensitive but lack specificity. Serologic
      screening (antinuclear antibody and rheumatoid factor) is advocated to rule out
      associated connective tissue disorders. Most patients with RS can be managed
      conservatively, with avoidance of cold exposure or hand warming. For those in
      whom conservative management is inadequate, a number of pharmacologic and
      surgical therapies have been used. Owing to lack of complete understanding of the
      underlying pathophysiology, targeted therapy has not been possible; rather,
      therapy has been focused on the use of general vasodilation strategies. In this
      review, the diagnosis, natural history, and current medical and invasive therapy
      are summarized. 

PMID- 25770639
TI  - Endovascular treatment of large vessel arteritis.
AB  - Large vessel vasculitis is very uncommon, particularly in Western countries, but
      can cause serious sequelae. Large vessel vasculitis is usually due to either
      Takayasu arteritis or giant cell arteritis. The available laboratory tests are
      nonspecific, so the diagnosis is often dependent on imaging findings. The
      location and pattern of vessel narrowing will usually define the type of
      vasculitis. Symptomatic vascular stenoses and occlusions can frequently be
      managed using balloon angioplasty. Familiarity with the indications for treatment
      and techniques and outcomes associated with angioplasty and surgical alternatives
      is essential when treating these rare disorders. 

PMID- 25770638
TI  - Polyarteritis nodosa.
AB  - The first description of polyarteritis nodosa (PAN) was in 1852 by Karl
      Rokitansky, a pathologist at the University of Vienna. The initial report
      describes a 23-year-old man who had a 5-day history of fever and diarrhea. Since
      then, the definition of PAN has evolved. The currently accepted definition of PAN
      comes from the 2012 Chapel Hill Conference, which classified PAN as a necrotizing
      arteritis not associated with antineutrophil cytoplasmic antibodies of medium or
      small arteries without glomerulonephritis or vasculitis in arterioles,
      capillaries, or venules. 

PMID- 25770640
TI  - The United States registry for fibromuscular dysplasia: new findings and breaking
      myths.
AB  - Fibromuscular dysplasia (FMD) is a nonatherosclerotic, noninflammatory arterial
      disease predominantly seen in women. Most FMD cases are classified as medial
      fibroplasia, which has the appearance of a string of beads on angiography. Until
      recently, FMD was thought to be seen in women in their 20s and 30s, with more
      than 60%-75% of cases occurring in the renal artery and 25% of cases in the
      carotid artery. Hypertension was regarded as the primary symptom seen in these
      patients followed by a small number of patients presenting with intracranial
      aneurysms with subarachnoid hemorrhage. The United States Registry of FMD, a
      patient registry, has broken many preconceived notions as well as provided more
      in-depth knowledge of this uncommon disorder. In this review, we discuss the
      findings of this registry and its use in understanding this disorder. In addition
      to the registry, we review other recent studies and future directions in the
      diagnosis and management of this disorder. 

PMID- 25770641
TI  - Validation of the completeness and accuracy of the Northern Ireland Cancer
      Registry.
AB  - BACKGROUND: It has been suggested that inaccuracies in cancer registries are
      distorting UK survival statistics. This study compared the Northern Ireland
      Cancer Registry (NICR) database of living patients, with independent data held by
      Northern Ireland's General Practitioners (GPs) to compare and validate the
      recorded diagnoses and dates held by the registry. METHODS: All 387 GP practice
      managers were invited to participate. 100 practices (25.84%) responded.
      Comparisons were made for 17,102 patients, equivalent to 29.08% of the living
      patients (58,798) extracted from the NICR between 1993 and 2010. RESULTS: There
      were no significant differences (p>0.05) between the responding and nonresponding
      GP patient profiles for age, marital status or deprivation score. However, the
      responding GPs included more female patients (p=0.02). NICR data accuracy was
      high, 0.08% of GP cancer patients (n=15) were not included in registry records
      and 0.02% (n=2) had a diagnosis date which varied more than 2 weeks from GP
      records (3 weeks and 5 months). The NICR had recorded two different tumour types
      and three different tumour statuses (benign vs. malignant) to the GPs.
      CONCLUSION: This comparison demonstrates a high level of accuracy within the NICR
      and that the survival statistics based on this data can be relied upon.

PMID- 25770642
TI  - Clinical features and prognostic factors in patients with head and neck cancer:
      Results from a multicentric study.
AB  - BACKGROUND: The purpose of this study is to evaluate whether demographics,
      lifestyle habits, clinical data and alcohol dehydrogenase polymorphisms rs1229984
      and rs1573496 associated with first primary head and neck (HNC) are associated
      with overall survival, recurrence, and second primary cancer (SPC). METHODS: We
      conducted a follow-up study in five centres including 801 cases. Hazard ratios
      (HRs) and 95% confidence intervals (CIs) were estimated for overall survival,
      recurrence and SPC. RESULTS: Five-years overall survival was 62% for HNC cases,
      55% for oral cavity, 53% for oropharynx, 41% for hypopharynx, and 71% for larynx.
      Predictors of survival were older ages (HR=1.18 for 5 years increase; CI: 1.07
      1.30), higher tumour stage (HR=4.16; CI: 2.49-6.96), and high alcohol consumption
      (HR=3.93; CI: 1.79-8.63). A combined therapy (HR=3.29; CI: 1.18-9.13) was
      associated with a worst prognosis for oral cavity cancer. The only predictor was
      higher tumour stage (HR=2.25; CI: 1.26-4.03) for recurrence, and duration of
      smoking (HR=1.91; CI: 1.00-3.68) for SPC. ADH1B rs1229984 polymorphism HRs for
      HNC and oesophageal cancer death and for alcohol related cancer death were 0.67
      (95% CI: 0.42-1.08), and 0.64 (95% CI: 0.40-1.03), respectively. CONCLUSIONS: The
      survival expectation differs among HNC sites. Increasing age and stage, and high
      alcohol consumption were unfavourable predictors of HNC survival overall.
      Duration of tobacco consumption before the first primary tumour was a risk factor
      for SPC.

PMID- 25770643
TI  - Depressive symptoms in heart failure: Independent prognostic factor or marker of
      functional status?
AB  - OBJECTIVE: The prognostic potential of depressive symptoms independent of somatic
      features of heart failure severity has repeatedly been demonstrated. However,
      patient-reported functional status has rarely been accounted for in these
      studies. Thus, it has remained unclear to what extent the predictive power of
      depressive symptoms may mirror functional status. We therefore aimed to evaluate
      the prognostic value of depressive symptoms adjusting for patient-reported
      functional status in a large, well-characterized sample of patients with systolic
      heart failure. METHODS: Eight hundred sixty-three patients, 67+/-12 years old,
      72% men, and 42% with New York Heart Association functional classes III/IV, who
      participated in the extended Interdisciplinary Network Heart Failure (INH) study
      were investigated. We assessed depressive symptoms using the Patient Health
      Questionnaire (PHQ-9) and patient-reported functional status with the Kansas City
      Cardiomyopathy Questionnaire (KCCQ). Data on survival was obtained after a follow
      up of 18 months (100% complete). RESULTS: Depressive symptoms predicted mortality
      risk (HR per PHQ-9 scale point=1.07, 95% CI 1.04-1.09, p<.001), even after
      adjustment for heart failure severity and co-morbidities (HR=1.04, 95% CI 1.01
      1.07, p=.017). However, they were no longer significant predictors (HR=1.01, 95%
      CI 0.98-1.05, p=0.46) after additional adjustment for patient-reported functional
      status, which proved predictive of mortality risk (HR=0.90, 95% CI 0.82-0.99,
      p=.025). CONCLUSION: Our results suggest that the association of depressive
      symptoms with functional status may at least partly explain the prognostic
      potential of depressive symptoms.

PMID- 25770644
TI  - The effect of KETODEX on the incidence and severity of emergence agitation in
      children undergoing adenotonsillectomy using sevoflurane based-anesthesia.
AB  - BACKGROUND: Postoperative emergency agitation (EA) is a common problem often
      observed in children undergoing general anesthesia. The purpose of this study was
      to evaluate whether a bolus of intraoperative low-dose ketamine followed by
      dexmedetomidine i.v. could reduce the incidence of EA in children undergoing
      adenotonsillectomy following sevoflurane-based anesthesia. METHODS: A total of 92
      children undergoing adenotonsillectomy, aged 3-7 years, were randomly allocated
      to receive either low-doseketamine 0.15 mg/kg followed by dexmedetomidine 0.3
      MUg/kg i.v. (KETODEX, n=45) or volume-matched normal saline (Control, n=47),
      about 10 min before the end of surgery. Anesthesia was induced and maintained
      with sevoflurane. Postoperative pain and EA were assessed with objective pain
      score (OPS) and the Pediatric Anesthesia Emergence Delirium scale (PAED),
      respectively. EA was defined as a PAED>=10 points. Recovery profile and
      postoperative complications were recorded. RESULT: The incidence and severity of
      EA was lower in KETODEX group than controls (11% vs. 47%) and (2% vs. 13%),
      respectively (P<0.05). The frequency of fentanyl rescue was lower in KETODEX
      group than in controls (13.3 vs. 38.3%, P<0.05). Heart rate during extubation was
      significantly higher in the control group compared with children who received
      KETODEX (P<0.05). The incidence of postoperative pain was significantly less in
      the KETODEX group (15.5% vs. 63.8%, P<0.05). Times to interaction and extubation
      were significantly longer in the KETODEX group (P<0.05). CONCLUSION: KETODEX
      reduces the incidence and severity of EA in children undergoing
      adenotonsillectomy following sevoflurane-based anesthesia and provided smooth
      extubation.

PMID- 25770645
TI  - Letter to the editor regarding "Plastic bronchitis associated with influenza".

PMID- 25770646
TI  - Prognostic factors for cases with no extracranial metastasis in whom brain
      metastasis is detected after resection of non-small cell lung cancer.
AB  - OBJECTIVES: This study aimed to determine prognostic factors associated with
      postrecurrence survival in cases with postoperative brain metastasis but with no
      extracranial metastasis in non-small cell lung cancer (NSCLC). MATERIAL AND
      METHODS: Between 1992 and 2012, a total of 2832 patients underwent surgical
      resection for NSCLC. Among those, 86 patients had postoperative brain metastasis
      as the initial recurrence. Those patients were retrospectively reviewed. RESULTS:
      The median follow-up time after the initial lung resection was 24.0 months
      (range, 2.0-126.0 months). The median overall survival after initial lung cancer
      resection was 25.0 months and the median overall postrecurrence survival was 11
      months. An initial lesion of adenocarcinoma (hazard ratio, 0.548; 95% confidence
      interval, 0.318 to 0.946; p=0.031), non-pneumonectomy, and a disease-free
      interval longer than 10.0 months (hazard ratio, 0.565; 95% confidence interval,
      0.321-0.995; p=0.048) from the initial lung resection to the diagnosis of brain
      metastasis positively related to a good postrecurrence survival. Solitary brain
      metastasis and a size of less than 3 cm for the largest brain lesion were also
      positive factors for postrecurrence survival. Systemic chemotherapy for brain
      metastasis (hazard ratio, 0.356; 95% confidence interval, 0.189-0.670; p=0.001)
      and local treatment of surgery and/or stereotactic radiosurgery (SRS) for brain
      lesions (hazard ratio, 0.321; 95% confidence interval, 0.138-0.747; p=0.008) were
      positive factors for better postrecurrence survival. CONCLUSION: In patients with
      brain metastasis after resection for NSCLC with no extracranial metastasis,
      adenocarcinoma histologic type, longer disease-free interval, systemic
      chemotherapy for brain metastasis and local treatment of surgery and/or SRS for
      brain metastasis are independent positive prognostic factors for postrecurrence
      survival.

PMID- 25770647
TI  - Cell-free expression of a functional pore-only sodium channel.
AB  - Voltage-gated sodium channels participate in the propagation of action potentials
      in excitable cells. Eukaryotic Navs are pseudo homotetrameric polypeptides,
      comprising four repeats of six transmembrane segments (S1-S6). The first four
      segments form the voltage-sensing domain and S5 and S6 create the pore domain
      with the selectivity filter. Prokaryotic Navs resemble these characteristics, but
      are truly tetrameric. They can typically be efficiently synthesized in bacteria,
      but production in vitro with cell-free synthesis has not been demonstrated. Here
      we report the cell-free expression and purification of a prokaryotic tetrameric
      pore-only sodium channel. We produced milligram quantities of the functional
      channel protein as characterized by size-exclusion chromatography, infrared
      spectroscopy and electrophysiological recordings. Cell-free expression enables
      advanced site-directed labelling, post-translational modifications, and special
      solubilization schemes. This enables next-generation biophysical experiments to
      study the principle of sodium ion selectivity and transport in sodium channels. 

PMID- 25770648
TI  - The antifungal activity of Artemisia sieberi essential oil from different
      localities of Iran against dermatophyte fungi.
AB  - Dermatophyte fungi are the most common cause of dermatophytosis in humans and
      animals. Artemisia sieberi is traditionally used for treatment of fungi related
      skin infections. In this investigation, we analyzed five samples of A. sieberi
      oils (different harvesting times and distinctive collecting locations) by GC-FID
      and GC-MS. The antifungal activities of A. sieberi oils were evaluated against
      different dermatophytes. The anti-elastase activities of essential oils were also
      evaluated. The results of analysis showed that the harvesting time and collecting
      location can affect the chemical compositions and oil yields. The best time for
      collecting the A. sieberi with high yield was spring season (January-February).
      There was no significant difference between the desirable anti-dermatophyte
      activities of A. sieberi oils with different chemical compositions. M. gypseum,
      T. rubrum and M. canis had more sensitivity than others to A. sieberi oils. The
      oils with higher amounts of alpha-thujone, beta-thujone showed the higher anti
      elastase activity. Therefore, A. sieberi can be used as topical antifungal agent
      for treatment of skin dermatophyte infections. 

PMID- 25770650
TI  - Implementation of a Diabetes Management Flow Sheet in a Long-Term Care Setting.
AB  - OBJECTIVES: Physicians lack clear guidance about adaptation of clinical practice
      guidelines for elderly institutionalized patients with diabetes. In a large long
      term care facility, a diabetes management flow sheet was trialed to determine
      which clinical parameters were found useful by clinicians in the management of
      diabetes in that setting. METHODS: Clinical practice guidelines for diabetes
      management were reviewed with attending physicians. Diabetes management flow
      sheets were distributed for all patients coded as having diabetes on their most
      recent minimum data sets. After a period of 14 months, flow sheet completion
      rates were ascertained and physicians were surveyed regarding the utility of the
      flow sheet. RESULTS: Initial flow sheet data were completed in full or in part
      for only 57% of the 121 study subjects; 39% of the subjects died within 14
      months. Quarterly follow-up data were completed for 58% of the flow sheets.
      CONCLUSIONS: The diabetes management flow sheet was not found to be useful by
      attending physicians as a chronic-disease management tool.

PMID- 25770649
TI  - Are genetic variants for tobacco smoking associated with cannabis involvement?
AB  - BACKGROUND: Cannabis users are highly likely to also be tobacco cigarette smokers
      and a proportion of this comorbidity is attributable to shared genetic
      influences. Three large meta-analyses of genomewide association studies (GWAS) of
      tobacco smoking have identified multiple genomewide significant (p<5*10(-8))
      single nucleotide polymorphisms (SNPs). We examine whether these SNPs are
      associated with tobacco smoking and with cannabis involvement in an independent
      sample. METHOD: Eleven SNPs associated with cigarettes per day (CPD), ever versus
      never smoking and current smoking/smoking cessation at p<5*10(-8) were selected
      from three published meta-analyses. Association analyses were conducted with
      similar tobacco smoking measures in 2716 European-American subjects from the
      Study of Addictions Genes and Environment (SAGE) and with lifetime and current
      cannabis use and DSM-IV cannabis abuse/dependence. RESULTS: Cannabis use and
      tobacco smoking correlated at 0.54. Rs16969968 in CHRNA5 (and its proxy,
      rs1051730 in CHRNA3) and rs1451240, a proxy for rs13280604 in CHRNB3, were
      associated with CPD after Bonferroni correction (p<0.006). rs1451240 was also
      associated with DSM-IV cannabis abuse/dependence. Rs6265 in BDNF was associated
      with smoking initiation, as in the original meta-analysis and also with lifetime
      cannabis use. Associations with cannabis involvement were no longer significant
      upon adjustment for the tobacco smoking measures. CONCLUSIONS: The modest
      associations between cannabis involvement and SNPs for tobacco smoking were not
      independent of the comorbidity between tobacco and cannabis involvement. Larger
      samples of individuals might be required to articulate the specific genetic
      architecture of cannabis involvement.

PMID- 25770651
TI  - Arab Adolescents: Health, Gender, and Social Context.
AB  - This article reviews the evidence about adolescent health in the Arab world,
      against the background of social, economic, and political change in the region,
      and with a particular focus on gender. For the literature review, searches were
      conducted for relevant articles, and data were drawn from national population-
      and school-based surveys and from the Global Burden of Disease project. In some
      parts of the Arab world, adolescents experience a greater burden of ill health
      due to overweight/obesity, transport injuries, cardiovascular and metabolic
      conditions, and mental health disorders than those in other regions of the world.
      Poor diets, insufficient physical activity, tobacco use, road traffic injuries,
      and exposure to violence are major risk factors. Young men have higher risks of
      unsafe driving and tobacco use and young women have greater ill-health due to
      depression. Several features of the social context that affect adolescent health
      are discussed, including changing life trajectories and gender roles, the
      mismatch between education and job opportunities, and armed conflict and
      interpersonal violence. Policy makers need to address risk factors behind
      noncommunicable disease among adolescents in the Arab region, including tobacco
      use, unhealthy diets, sedentary lifestyles, unsafe driving, and exposure to
      violence. More broadly, adolescents need economic opportunity, safe communities,
      and a chance to have a voice in their future. 

PMID- 25770652
TI  - Association between mandibular condylar position and clinical dysfunction index.
AB  - OBJECTIVES: Condylar position in the glenoid fossa has been associated with
      temporomandibular disorders. The purpose of the present study was to investigate
      the correlation between clinical dysfunction index (Di) and mandibular condylar
      position in patients with temporomandibular joint dysfunction (TMD) using cone
      beam computed tomography (CBCT). METHODS: In this cross-sectional study,
      participants were recruited from the Department of Maxillofacial Radiology at
      Shiraz Dental University in Iran. The condylar position was assessed on the CBCT
      images of 120 temporomandibular joints in 60 patients with TMD. Patients were
      divided into 3 groups based on Helkimo's clinical Di. The chi-square test was
      used to correlate degree of the Helkimo's Di with the mandibular condylar
      position. The p value was set at 0.05. RESULTS: A total of 60 patients (42 women
      and 18 men; mean age, 33.4 years) participated in this study. Significant
      differences in condylar position were found among the 3 groups (Di I, II, and
      III) (p < 0.05). Patients with mild to moderate TMD were found to have anteriorly
      and concentric seated condyles. Posteriorly seated condyles were found in
      patients with severe TMD. CONCLUSION: Condylar position is associated with
      different severity of TMD.

PMID- 25770653
TI  - Stereotactic body radiotherapy for oligometastatic disease.
AB  - Stereotactic body radiotherapy (SBRT) is now an established therapy in stage I
      lung cancer with comparable local control rates to surgical resection. Owing to
      the conformity of treatment dose delivery and with appropriate fractionation
      considerations, minimal side-effects to surrounding normal tissues are observed
      in most patients. SBRT is now being used in the treatment of oligometastatic
      disease, alone or alongside systemic therapy. At present there is a paucity of
      evidence available showing a clinical benefit, but several international studies
      are being set-up or have started recruitment. This overview considers the
      clinical entity of an oligometastatic state, discusses the role of SBRT in the
      management of oligometastatic disease and discusses potential novel therapy
      combinations with SBRT.

PMID- 25770654
TI  - Sorption and degradation of triclosan in sediments and its effect on microbes.
AB  - Sorption and degradation behavior of triclosan (TCS) and its effect on microbes
      were studied in three sediments spiked at different concentration levels (1, 10,
      and 100 MUg g(-1)). TCS showed a strong affiliation to all the sediments with
      linear adsorption coefficients (Kd) that varied from 220 to 1092 L g(-1), and the
      adsorption capacity is related to the total organic carbon (TOC) contents of the
      sediments. The half-lives of TCS varied from 55 to 239 days, and were longer in
      sediment with higher Kd. TCS showed minor effect on the activities of fluorescein
      diacetate hydrolase, dehydrogenase, alkaline phosphatase, and urease in the 1 MUg
      g(-1) treatment, but at higher levels, a short-term effect was observed followed
      by a rapid recovery except the urease activity in sediment with the lowest
      adsorption capacity. PCA plots of phospholipid fatty acid showed that the
      phenotypic community in sediments with low TOC were more sensitive to TCS. A
      positive relation between bacterial biomass and total microbial biomass suggests
      that changes of bacteria biomass were responsible for changes of total microbial
      biomass in treatments. Denaturing gradient gel electrophoresis analysis of the
      16S rDNA showed that the bacterial community structure deviated further away from
      the control at higher TCS concentration levels, with similarity coefficients in
      Un-weighted Pair Group Mathematics Average clustering between control and 100 MUg
      g(-1) treatment varied from 0.38 to 0.73. Both degradation rate and toxic effects
      of TCS decreased in sediment with higher sorption capacity, which can be
      attributed to a reduced bioavailablity.

PMID- 25770655
TI  - Antioxidant enzymes are induced by phenol in the marine microalga Lingulodinium
      polyedrum.
AB  - Knowing the impacts of different anthropogenic activities on ecosystems promotes
      preservation of aquatic organisms. Aiming to facilitate the identification of
      polluted or contaminated areas, the study of microalga Lingulodinium polyedrum in
      phenol-containing medium comprises the determination of toxic and metabolic
      phenol effects, featuring a possible use of this microorganism as bioindicator
      for this pollutant. Marine microalga L. polyedrum exposure to phenol increases
      superoxide dismutase (SOD) and catalase (CAT) activities. The 20% and 50%
      inhibitory concentrations (IC20 and IC50) of cells exposed to phenol were 40
      MUmol L(-1) and 120 MUmol L(-1), respectively. Phenol biodegradation by L.
      polyedrum was 0.02 MUmol h(-1)cell(-1), and its biotransformation was catalyzed
      by glutathione S-transferase (GST), phenol hydroxylase and catechol 2,3
      dihydroxygenase metabolic pathways. Phenol exposure produced the metabolites 2
      hydroxymuconic semialdehyde acid, 1,2-dihydroxybenzene (catechol), and 2-oxo-4
      pentenoic acid; also, it induced the activity of key antioxidant biomarker
      enzymes SOD and CAT by three folds compared to that in the controls. Further,
      phenol decreased the glutathione/oxidized glutathione ratio (GSH/GSSG),
      highlighting the effective glutathione oxidation in L. polyedrum. Overall, our
      results suggest that phenol alters microalga growth conditions and microalgae are
      sensitive bioindicators to pollution by phenol in marine environments.

PMID- 25770657
TI  - [Laughter-induced syncope: Description of a case and review of the literature].

PMID- 25770656
TI  - Responses of Lyngbya wollei to algaecide exposures and a risk characterization
      associated with their use.
AB  - To make informed decisions regarding management of noxious algal growths, water
      resource managers require information on responses of target and non-target
      species to algaecide exposures. Periodic treatments of Phycomycin(r)-SCP (sodium
      carbonate peroxyhydrate) followed by Algimycin(r)-PWF (gluconate and citrate
      chelated copper) to control Lyngbya wollei growths for ten years provided an
      opportunity for a risk evaluation of treated coves in Lay Lake, AL. Abiotic
      sediment characteristics (acid soluble copper concentrations, acid volatile
      sulfides, percent organic matter and cation exchange capacity) and survival of
      Hyalella azteca and Chironomus dilutus were measured in sediment samples from
      treated and untreated coves to assess the bioavailability of potential copper
      residuals. In laboratory studies to seek a more effective approach for managing
      the growth of Lyngbya, six algaecide treatments consisting of combinations of
      copper-based algaecides (Cutrine(r)-Ultra, Clearigate(r) and Algimycin(r)- PWF),
      a hydrogen peroxide based algaecide (Phycomycin(r)-SCP) and an adjuvant (Cide
      Kick II) were assessed for efficacy in controlling L. wollei sampled from Lay
      Lake. The most efficient algaecide treatment was determined based on post
      treatment algal wet weight and visual observations of responses to exposures. To
      estimate the margin of safety for non-target organisms, Pimephales promelas was
      exposed to the most efficacious treatment and a treatment of Phycomycin(r)-SCP
      followed by Algimycin(r)-PWF. Results from sediment experiments demonstrated that
      there were no measureable copper residuals and no adverse effects on H. azteca
      and C. dilutus from sediments following ten years of copper-based algaecide
      treatments. Based on the laboratory results, a treatment of Phycomycin(r)-SCP at
      10.1 mg H2O2/L followed by Cide-Kick II at 0.2 mg/L and Algimycin(r)- PWF at 0.26
      mg Cu/L could control the growth of Lyngbya wollei from Lay Lake, AL and enhance
      the margin of safety for non-target species (e.g. P. promelas).

PMID- 25770658
TI  - CMV infection of human sinusoidal endothelium regulates hepatic T cell
      recruitment and activation.
AB  - BACKGROUND & AIMS: Human cytomegalovirus infection (HCMV) is associated with an
      increased morbidity after liver transplantation, by facilitating allograft
      rejection and accelerating underlying hepatic inflammation. We hypothesized that
      human hepatic sinusoidal endothelial cells infected with HCMV possess the
      capacity to modulate allogeneic T cell recruitment and activation, thereby
      providing a plausible mechanism of how HCMV infection is able to enhance hepatic
      immune activation. METHODS: Human hepatic sinusoidal endothelial cells were
      isolated from explanted livers and infected with recombinant endotheliotropic
      HCMV. We used static and flow-based models to quantify adhesion and
      transendothelial migration of allogeneic T cell subsets and determine their post
      migratory phenotype and function. RESULTS: HCMV infection of primary human
      hepatic sinusoidal endothelial cells facilitated ICAM-1 and CXCL10-dependent CD4
      T cell transendothelial migration under physiological levels of shear stress.
      Recruited T cells were primarily non-virus-specific CXCR3(hi) effector memory T
      cells, which demonstrated features of LFA3-dependent Th1 activation after
      migration, and activated regulatory T cells, which retained a suppressive
      phenotype following transmigration. CONCLUSIONS: The ability of infected hepatic
      endothelium to recruit distinct functional CD4 T cell subsets shows how HCMV
      facilitates hepatic inflammation and immune activation and may simultaneously
      favor virus persistence.

PMID- 25770659
TI  - Breast tumor kinase/protein tyrosine kinase 6 (Brk/PTK6) activity in normal and
      neoplastic biliary epithelia.
AB  - BACKGROUND & AIMS: Breast tumor kinase (BRK) augments proliferation and promotes
      cell survival in breast cancers via interactions with SH2 and SH3 ligand
      containing proteins, such as receptor tyrosine kinases (RTK; e.g. EGFR,
      ErbB2/neu). Since RTK contribute to cholangiocarcinoma (CC) evolution we probed
      BRK protein expression and function in normal and CC livers. METHODS:
      Immunohistochemical staining of normal livers and CC (n=93) in a tissue
      microarray and three CC and an immortalized human cholangiocyte cell lines (real
      time PCR, Western blotting, siRNA) were used to study the functional
      relationships between BRK, EGFR, ErbB2, SAM68, and SPRR2a. RESULTS: BRK protein
      was expressed in normal human intrahepatic bile ducts; all CC cell lines and a
      majority of CC showed strong BRK protein expression. Multiplex
      immunostaining/tissue cytometry and immunoprecipitation studies showed: 1) BRK co
      localized with EGFR and ErbB2/neu; 2) BRK(high)/EGFR(high)-co-expressing CC cells
      had significantly higher Ki67 labeling and; 3) stronger BRK protein expression
      was seen in perihilar and distal CC than intrahepatic CC and directly correlated
      with CC differentiation. In cell lines, BRK expression augmented proliferation in
      response to exogenous EGF, whereas BRK siRNA significantly reduced growth. The
      SH3 ligand-containing, SPRR2A activated pTyr342 BRK, which in turn,
      phosphorylated SAM68, causing nuclear localization and increased cell
      proliferation similar to observations in breast cancers. CONCLUSION: BRK
      expression in a majority of CC can interact with RTK, augmenting growth and
      interfering with proliferation inhibitors (SAM68). Therapeutically targeting BRK
      function (in addition to RTK) should be of benefit for CC treatment.

PMID- 25770660
TI  - Machine perfusion in liver transplantation as a tool to prevent non-anastomotic
      biliary strictures: Rationale, current evidence and future directions.
AB  - The high incidence of non-anastomotic biliary strictures (NAS) after
      transplantation of livers from extended criteria donors is currently a major
      barrier to widespread use of these organs. This review provides an update on the
      most recent advances in the understanding of the etiology of NAS. These new
      insights give reason to believe that machine perfusion can reduce the incidence
      of NAS after transplantation by providing more protective effects on the biliary
      tree during preservation of the donor liver. An overview is presented regarding
      the different endpoints that have been used for assessment of biliary injury and
      function before and after transplantation, emphasizing on methods used during
      machine perfusion. The wide spectrum of different approaches to machine perfusion
      is discussed, including the many different combinations of techniques,
      temperatures and perfusates at varying time points. In addition, the current
      understanding of the effect of machine perfusion in relation to biliary injury is
      reviewed. Finally, we explore directions for future research such as the
      application of (pharmacological) strategies during machine perfusion to further
      improve preservation. We stress the great potential of machine perfusion to
      possibly expand the donor pool by reducing the incidence of NAS in extended
      criteria organs. 

PMID- 25770661
TI  - Targeting signal transduction pathways which regulate necrosis in acetaminophen
      hepatotoxicity.

PMID- 25770662
TI  - Myeloperoxidase impairs the contractile function in isolated human
      cardiomyocytes.
AB  - We set out to characterize the mechanical effects of myeloperoxidase (MPO) in
      isolated left-ventricular human cardiomyocytes. Oxidative myofilament protein
      modifications (sulfhydryl (SH)-group oxidation and carbonylation) induced by the
      peroxidase and chlorinating activities of MPO were additionally identified. The
      specificity of the MPO-evoked functional alterations was tested with an MPO
      inhibitor (MPO-I) and the antioxidant amino acid Met. The combined application of
      MPO and its substrate, hydrogen peroxide (H2O2), largely reduced the active force
      (Factive), increased the passive force (Fpassive), and decreased the Ca(2+)
      sensitivity of force production (pCa50) in permeabilized cardiomyocytes. H2O2
      alone had significantly smaller effects on Factive and Fpassive and did not alter
      pCa50. The MPO-I blocked both the peroxidase and the chlorinating activities,
      whereas Met selectively inhibited the chlorinating activity of MPO. All of the
      MPO-induced functional effects could be prevented by the MPO-I and Met. Both H2O2
      alone and MPO + H2O2 reduced the SH content of actin and increased the
      carbonylation of actin and myosin-binding protein C to the same extent. Neither
      the SH oxidation nor the carbonylation of the giant sarcomeric protein titin was
      affected by these treatments. MPO activation induces a cardiomyocyte dysfunction
      by affecting Ca(2+)-regulated active and Ca(2+)-independent passive force
      production and myofilament Ca(2+) sensitivity, independent of protein SH
      oxidation and carbonylation. The MPO-induced deleterious functional alterations
      can be prevented by the MPO-I and Met. Inhibition of MPO may be a promising
      therapeutic target to limit myocardial contractile dysfunction during
      inflammation. 

PMID- 25770663
TI  - Bartter/Gitelman syndromes as a model to study systemic oxidative stress in
      humans.
AB  - Reactive oxygen species (ROS) are intermediates in reduction-oxidation reactions
      that begin with the addition of one electron to molecular oxygen, generating the
      primary ROS superoxide, which in turn interacts with other molecules to produce
      secondary ROS, such as hydrogen peroxide, hydroxyl radical, and peroxynitrite.
      ROS are continuously produced during metabolic processes and are deemed to play
      an important role in cardiovascular diseases, namely, myocardial hypertrophy and
      fibrosis and atherosclerosis, via oxidative damage of lipids, proteins, and
      deoxyribonucleic acid. Angiotensin II (Ang II) is a potent vasoactive agent that
      also exerts mitogenic, proinflammatory, and profibrotic effects through several
      signaling pathways, in part involving ROS, particularly superoxide and hydrogen
      peroxide. Moreover, Ang II stimulates NADPH oxidases, leading to higher ROS
      generation and oxidative stress. Bartter/Gitelman syndrome patients, despite
      elevated plasma renin activity, Ang II, and aldosterone levels, exhibit reduced
      peripheral resistance, normal/low blood pressure, and blunted pressor effect of
      vasoconstrictors. In addition, notwithstanding the activation of the renin
      angiotensin system and the increased plasma levels of Ang II, these patients
      display decreased production of ROS, reduced oxidative stress, and increased
      antioxidant defenses. In fact, Bartter/Gitelman syndrome patients are
      characterized by reduced levels of p22(phox) gene expression and undetectable
      plasma peroxynitrite levels, while showing increased plasma antioxidant power and
      expression of antioxidant enzymes, such as heme oxygenase-1. In conclusion,
      multifarious data suggest that Bartter and Gitelman syndrome patients are a model
      of low oxidative stress and high antioxidant defenses. The contribution offered
      by the study of these syndromes in elucidating the molecular mechanisms
      underlying this favorable status could offer chances for new therapeutic targets
      in disease characterized by high levels of reactive oxygen species. 

PMID- 25770664
TI  - A rapid in vivo zebrafish model to elucidate oxidative stress-mediated PCB126
      induced apoptosis and developmental toxicity.
AB  - Dioxin-like 3,3',4,4',5-pentachlorobiphenyl (PCB126) is one of the most potent
      and widespread environmental pollutants. Although PCB126-induced toxicity is
      related to the aryl hydrocarbon receptor pathway, there is still no study that
      has constructed an in vivo visual model to clarify the role of the Nrf2/ARE
      signaling pathway in the oxidative stress mechanism of PCB126-induced toxicity.
      In the present study, an in vivo zebrafish model of nrf2a fused to enhanced green
      fluorescent protein (nrf2a-eGFP) was constructed. The zebrafish embryos
      microinjected with nrf2a-eGFP (72h postfertilization) were exposed to various
      concentrations of PCB126 (0, 25, 50, 100, 200MUg/L) or 30mMN-acetylcysteine
      (NAC)+200MUg/L PCB126. After 72h exposure, PCB126 significantly increased the
      malformation rates and induced eGFP expression in a dose-dependent manner in
      several zebrafish tissue types. The distribution of eGFP fluorescence coincided
      with developmental deformity sites. NAC pretreatment effectively counteracted
      PCB126-induced developmental toxicity including heart rate, pericardial edema,
      and body length. The highest PCB126 dose, 200MUg/L, produced marked apoptosis in
      the eye, gill, and trunk detected by the terminal deoxynucleotidyl transferase
      mediated dUTP nick-end labeling assay. At 48 and 72h exposure, 200MUg/L PCB126
      affected glutathione metabolism as evidenced by decreased glutathione and
      increased glutathione disulfide concentrations, indicative of oxidative stress.
      These effects were also counteracted by NAC pretreatment. Furthermore, the Nrf2
      regulated genes gclc, gpx, gstp1, and hmox1 were significantly induced at 24, 48,
      and 72h at the highest PCB126 exposures but not in the NAC-pretreated group. In
      addition, a significant increase in ROS generation was detected in zebrafish
      larvae at 72h PCB126 exposure, which might offer a link for future mechanistic
      studies. Collectively, these data suggest that PCB126-induced developmental
      toxicity and apoptosis in the nrf2a-eGFP-injected zebrafish model are due to
      oxidative stress mediated by disruption to glutathione metabolism and changes in
      Nrf2-regulated gene expression. 

PMID- 25770665
TI  - Incremental prognostic value of echocardiographic strain and its association with
      mortality in cancer patients.
AB  - BACKGROUND: Left ventricular global longitudinal systolic strain (GLS) has been
      shown to be superior to ejection fraction in detecting subclinical dysfunction in
      patients with cancer and predicting mortality in patients with cardiovascular
      disease. Cancer-related fatigue is common in the later stages of neoplastic
      malignancies and may be indicative of nonovert heart failure. The aim of this
      study was to determine whether reduced strain by echocardiography was associated
      with all-cause mortality in a cancer cohort. METHODS: In this retrospective
      study, 120 patients with cancer undergoing or scheduled to undergo chemotherapy
      and with normal ejection fractions (>50%) underwent assessments of GLS. GLS was
      derived by averaging all speckle-tracking strain segments of the left ventricle.
      RESULTS: Over an average follow-up period of 21.6 +/- 13.9 months, 57 of 120
      patients died. Univariate predictors of all-cause mortality (P < .10) were
      Eastern Cooperative Oncology Group performance status, male sex, hematologic
      malignancy, beta-blocker use, and GLS. Multivariate analysis of all significant
      univariate variables showed that Eastern Cooperative Oncology Group performance
      status (hazard ratio, 2.12; 95% confidence interval, 1.54-2.92; P < .001), male
      sex (hazard ratio, 1.93; 95% confidence interval, 1.14-3.27; P = .014), and GLS
      (hazard ratio, 0.89; 95% confidence interval, 0.81-0.97; P = .012) were
      significantly and independently associated with mortality. Stepwise analysis of
      the multivariate associations showed an increase in the global chi(2) value after
      adding GLS (P = .011) to significant clinical variables. CONCLUSIONS: Eastern
      Cooperative Oncology Group performance status, male sex, and GLS were
      significantly associated with all-cause mortality in patients with cancer with
      normal ejection fractions receiving chemotherapy. Adding GLS to significant
      clinical variables provided incremental prognostic information.

PMID- 25770666
TI  - Covered stents for endovascular repair of iatrogenic injuries of iliac and
      femoral arteries.
AB  - BACKGROUND: The growing number of complex endovascular procedures is expected to
      increase the risk of iatrogenic injuries of peripheral arteries. A strategy of
      percutaneous transluminal angioplasty (PTA) with covered stent (CS) may represent
      a valuable alternative to open surgery. However, systematic evaluations of CS in
      this setting represent a scientific gap. In the present study, we investigate the
      procedural and clinical outcomes associated with PTA and CS implantation to
      repair iatrogenic injuries of peripheral arteries. METHODS: All patients
      undergoing PTA with CS for endovascular repair of iatrogenic injuries of
      peripheral arteries between August 2010 and July 2013 at our Institution were
      retrospectively analyzed. The primary endpoint was the technical success.
      Secondary endpoints were in-hospital mortality and cumulative death, target
      lesion revascularization (TLR), amputation and major stroke at 12-month follow
      up. RESULTS: During the period of observation, a total of 30 patients underwent
      PTA with either self-expandable (43.3%) or balloon-expandable CS (56.7%) for
      iatrogenic injuries of peripheral arteries. Injuries consisted of
      perforation/rupture (76.7%), arteriovenous fistula (16.7%) and pseudoaneurysm
      (6.7%) of iliac-femoral arteries. Technical success was achieved in all cases.
      Median follow-up was 409days [210-907]. The incidence of in-hospital mortality
      was 10.0%. At 12-month follow-up, the incidence of death, TLR, amputation and
      major stroke was 20.0%, 17.0%, 3.3% and 6.7%, respectively. CONCLUSION: The use
      of covered stents for endovascular repair of iatrogenic injuries of peripheral
      arteries shows a high technical success and may be alternative to surgery.
      Further studies with larger populations are needed to confirm these preliminary
      findings.

PMID- 25770667
TI  - Long-term variation in hemoglobin concentration in nestling great tits Parus
      major.
AB  - Several studies have previously proposed that blood hemoglobin concentration in
      nestling passerines is a reliable index of individual condition and nutritional
      state. In this paper we present results concerning variation in hemoglobin
      concentration in the blood of ca. 14-day-old nestling great tits Parus major in
      central Poland in an 11-year-long period, 2003-2013, in two distinct habitat
      types: urban park and deciduous forest. The most important findings of the study
      were: (i) variation in hemoglobin concentration was consistent within broods,
      (ii) hemoglobin concentration of nestlings varied markedly across years, (iii)
      hemoglobin concentration was significantly higher in the forest study site which
      is richer in terms of food abundance during the short period of tits breeding
      season and (iv) high hemoglobin level was a predictor of nestling survival from
      hatching to fledging. 

PMID- 25770668
TI  - Variation in blood serum antifreeze activity of Antarctic Trematomus fishes
      across habitat temperature and depth.
AB  - High latitude waters in the Southern Ocean can be near their freezing point and
      remain ice-covered throughout the year whereas lower latitude Southern Ocean
      waters have seasonal ice coverage and comparatively large (6  degrees C) annual
      temperature changes. The genus Trematomus (suborder Notothenioidei) is regarded
      primarily as a high latitude group because of its abundance there, they also
      inhabit the warmer regions in smaller numbers. Freeze avoidance in the
      notothenioids is linked to the presence of two antifreeze proteins (AFPs); the
      antifreeze glycoproteins (AFGPs) and antifreeze potentiating protein (AFPP), both
      of which adsorb to internal ice crystals inhibiting growth. Both high and low
      latitude trematomids possess sufficient AFP to lower their blood freezing point
      below that of seawater (-1.9  degrees C). We investigated the contributions of
      AFGPs and AFPP to the blood freezing point depression to determine how they
      varied with depth, water temperature, and the presence of ice. High latitude
      trematomids had lower blood freezing points than those inhabiting lower latitude
      waters indicating differences in their freeze avoidance capacities. Lower
      freezing points were associated with higher levels of antifreeze activity due to
      higher levels of both AFGP and AFPP. Populations of Trematomus hansoni and
      Trematomus bernacchii from shallow depths appear more freeze avoidant than
      populations inhabiting deep, ice-free water based on their lower freezing points
      and higher antifreeze activities. Gel electrophoresis of the trichloroacetic acid
      soluble AFGPs indicates that only high molecular weight isoforms, which
      contribute more to AFGP activity, vary across species as well as between
      individuals of a species.

PMID- 25770669
TI  - Characterization, expression, and function analysis of gonad-inhibiting hormone
      in Oriental River prawn, Macrobrachium nipponense and its induced expression by
      temperature.
AB  - Gonad-inhibiting hormone (GIH) is a member of crustacean hyperglycemic hormone
      family and plays a major role in regulating reproduction in crustaceans. In this
      study, a full-length cDNA of GIH of Oriental River prawn, Macrobrachium
      nipponense (Mn-GIH) was cloned from the eyestalk. A 1350 bp full-length Mn-GIH
      cDNA harbored 336 bp of an open reading frame encoding signal peptide of 112
      amino acid residues. Sequence analysis revealed that the overall cDNA sequence
      and specific functional sites of Mn-GIH were highly conserved with those in other
      crustacean species. Expression analysis by quantitative real-time PCR
      demonstrated its tissue-specific, larval developmental stage-specific, and ovary
      developmental stage-specific expression pattern, respectively. The RNAi by GIH-ds
      RNA in vivo injection was effective in this study and resulted a 50% (day 1), 83%
      (day 5) and 63% (day 9) down-regulation compared to control. The obvious changes
      of gonad somatic index (GSI) rate also provided strong evidence to the inhibition
      effects of GIH on ovary maturation and spawning. Four temperature gradients (12 
      degrees C +/- 1  degrees C, 17  degrees C +/- 1  degrees C, 22  degrees C +/- 1 
      degrees C, 27  degrees C +/- 1  degrees C) were set to imitate the temperature in
      breeding and non-breeding seasons. The observed expression profiles suggest that
      Mn-GIH did not display a high level expression as supposed to maintain an
      immature ovary state under low temperature (12  degrees C). The results indicated
      that GIH was probably activated to concentrating and working by a proper
      temperature before reaching to breeding season.

PMID- 25770670
TI  - Intermediate pyrolysis of agro-industrial biomasses in bench-scale pyrolyser:
      Product yields and its characterization.
AB  - Pyrolysis of woody biomass, agro-residues and seed was carried out at 500 +/- 10 
      degrees C in a fixed bed pyrolyser. Bio-oil yield was found varying from 20.5% to
      47.5%, whereas the biochar and pyrolysis gas ranged from 27.5% to 40% and 24.5%
      to 40.5%, respectively. Pyrolysis gas was measured for flame temperature along
      with CO, CO2, H2, CH4 and other gases composition. HHV of biochar (29.4 MJ/kg)
      and pyrolitic gas (8.6 MJ/kg) of woody biomass was higher analogous to sub
      bituminous coal and steam gasification based producer gas respectively, whereas
      HHV of bio-oil obtained from seed (25.6 MJ/kg) was significantly more than husks,
      shells and straws. TGA-DTG studies showed the husks as potential source for the
      pyrolysis. Bio-oils as a major by-product of intermediate pyrolysis have several
      applications like substitute of furnace oil, extraction of fine chemicals,
      whereas biochar as a soil amendment for enhancing soil fertility and gases for
      thermal application.

PMID- 25770671
TI  - Thinking Well: A randomised controlled feasibility study of a new CBT therapy
      targeting reasoning biases in people with distressing persecutory delusional
      beliefs.
AB  - BACKGROUND AND OBJECTIVES: Delusional beliefs with persecutory content are common
      in psychosis, but difficult to treat. Interventions targeting hypothesised causal
      and maintaining factors have been proposed as a way of improving therapy. The
      current study is a feasibility randomised controlled trial of the 'Thinking Well
      (TW)' intervention: This novel approach combines the recently developed Maudsley
      Review Training Programme (MRTP), with additional, focussed cognitive-behavioural
      therapy sessions. METHODS: 31 participants with distressing persecutory delusions
      and schizophrenia spectrum disorders were randomised to TW or to treatment as
      usual in a 2:1 ratio. Participants completed outcome assessments at 0 (baseline),
      1 (post-MRTP), 6 (post-TW) and 8 (follow-up) weeks. Key outcomes included belief
      flexibility, paranoia, and delusional conviction and distress. Participants
      allocated to TW completed the MRTP package and four CBT sessions with a clinical
      psychologist. RESULTS: Recruitment proved feasible. Participants reported the
      intervention was relevant and had resulted in positive changes in thinking and
      mood, which they could use in everyday life. Treatment effects were moderate
      large for key outcomes including belief flexibility, paranoia conviction and
      distress. The additional TW sessions appeared to confer benefits over MRTP alone.
      LIMITATIONS: Assessments were not carried out blind to treatment condition.
      Recruitment was opportunistic, from an identified pool of research participants.
      Finally, a few participants had already completed the MRTP as part of a previous
      study. CONCLUSIONS: The TW intervention appears to be feasible and acceptable to
      participants, and the effects of treatment are promising. A fully powered
      randomised controlled trial of the intervention is warranted.

PMID- 25770672
TI  - Reconstitution and characterization of antibody repertoires of HIV-1-infected
      "elite neutralizers".
AB  - Around 3-5% HIV-1-infected individuals develop high titers of broadly
      neutralizing HIV-1 antibodies (bnAbs) during chronic infection. However,
      monoclonal antibodies (mAbs) isolated from such "elite neutralizers" do not, in
      most cases, depict the serum IgGs in neutralizing the virus. We hypothesize that
      HIV-1-specific antibodies in infected subjects may work in a population manner in
      containing the virus in vivo, and in vitro reconstituted antibody repertoires of
      "elite neutralizers" may mimic the sera in binding and neutralizing the virus.
      This study aims to investigate the antibody repertoires of three such "elite
      neutralizers" by reconstituting the immune antibody repertories in vitro followed
      by a comparative study of the recombinant library IgGs with the corresponding
      serum IgGs. We found that the recombinant library IgGs were much weaker than the
      serum IgGs in binding to envelope glycoproteins (Envs) and in neutralizing the
      virus and inhibiting Env-mediated cell-cell fusion. However, the sorted libraries
      composing of HIV-1-specific neutralizing antibodies (nAbs) in the three
      recombinant libraries exhibited comparable binding and inhibitory activities, as
      well as antibody-dependent cell-mediated cytotoxicity (ADCC), to the serum IgGs.
      The sorted library IgGs further showed neutralization profiles which are similar
      to those of the serum IgGs, but they were overall less potent than the serum
      IgGs. The sorted library IgGs and the serum IgGs bound weakly to the resurfaced
      Env gp120, RSC3, and did not bind to the CD4 binding site (CD4bs) knock-out
      mutant, DeltaRSC3. Profiling with VRC01 binding site knock-out site mutants of
      gp120BaL indicates that, if there are any CD4bs bnAbs in these sera, they are
      more likely b12-like, but not VRC01-class bnAbs. Our results suggest that HIV-1
      specific Ab-expressing B cells, especially potent nAb-expressing B cells may not
      be rich in the B cell repertoires of "elite neutralizers", but they may be highly
      active in producing nAbs in vivo. In vitro reconstituted HIV-1 nAb repertoires of
      "elite neutralizers" may be used in passive immunization to prevent HIV-1
      infection. HIV-1 vaccine immunogens may be designed to target multiple
      neutralizing determinants to stimulate multiple B cell populations. HIV-1
      specific antibodies induced by such immunogens may work in combination or
      synergistically in containing the virus. 

PMID- 25770673
TI  - Short communication: molecular characterization of dog and cat p65 subunits of NF
      kappaB.
AB  - Nuclear factor kappa B (NF-kappaB) plays an important role in the immune system.
      The p65 subunit is an important part of NF-kappaB unit, and studies of dog and
      cat p65 subunits of NF-kappaB (dp65 and cp65) are important in understanding
      their immune function. In this study, we described the molecular characterization
      of dp65 and cp65. The dp65 and cp65 complementary DNA encoded 542 and 555 amino
      acids, respectively, showing a high sequence homology with the mammalian p65
      subunit (>87.5%). Quantitative polymerase chain reaction revealed that the p65
      messenger RNA is highly expressed in the dog stomach and cat heart and adipose
      tissue. Functional NF-kappaB promoter-luciferase reporter vectors revealed that
      our isolated dp65 and cp65 cDNA encodes a functionally active protein.
      Transiently expressed dp65 and cp65 up-regulated pro-inflammatory cytokine
      expression levels in dog and cat, respectively. These findings suggest that dp65
      and cp65 play important roles in regulating immune function. 

PMID- 25770674
TI  - Allergy testing in the diagnosis of asthma.

PMID- 25770675
TI  - Biomarkers in idiopathic pulmonary fibrosis: picking the winners for trials.

PMID- 25770676
TI  - Longitudinal change in collagen degradation biomarkers in idiopathic pulmonary
      fibrosis: an analysis from the prospective, multicentre PROFILE study.
AB  - BACKGROUND: Idiopathic pulmonary fibrosis, a progressive and inevitably fatal
      disorder, has a highly variable clinical course. Biomarkers that reflect disease
      activity are urgently needed to inform patient management and for use as
      biomarkers of therapeutic response (theragnostic biomarkers) in clinical trials.
      We aimed to determine whether dynamic change in markers of extracellular matrix
      (ECM) turnover predicts progression of idiopathic pulmonary fibrosis as
      determined by change in forced vital capacity and death. METHODS: In this ongoing
      prospective, multicentre, observational cohort study (PROFILE), participants with
      idiopathic pulmonary fibrosis or idiopathic non-specific interstitial pneumonia
      diagnosed within the preceding 6 months were recruited from two coordinating
      centres (Nottingham, UK, and, Royal Brompton Hospital, London, UK). Serum samples
      were prospectively collected at baseline, 1 month, 3 months, and 6 months and
      were analysed for a panel of novel matrix metalloprotease (MMP)-degraded ECM
      proteins, by ELISA-based, neoepitope assay. 11 neoepitopes were tested in a
      discovery cohort of 55 patients to identify biomarkers of sufficient rigour for
      more detailed analyses. Eight were then further assessed in a validation cohort
      of 134 patients with 50 age-matched and sex-matched controls. Changes in
      biomarker concentrations were related to subsequent progression of idiopathic
      pulmonary fibrosis (defined as death or decline in forced vital capacity >10% at
      12 months after study enrolment) using a repeated measures model. The PROFILE
      study is registered on ClinicalTrials.gov, numbers NCT01134822 and NCT01110694.
      FINDINGS: Of 214 eligible participants recruited between Sept 1, 2010, and March
      31, 2012, 189 had a confirmed diagnosis of idiopathic pulmonary fibrosis and were
      included in subsequent analyses. In the discovery cohort, mean concentrations of
      seven neoepitopes (BGM, p=0.009; C1M, p=0.009; C3M, p=0.046; C6M, p=0.032; CRPM,
      p=0.008; ELM2, p=0.02; and VICM, p=0.0007) differed significantly between healthy
      controls and participants with idiopathic pulmonary fibrosis. Baseline
      concentrations of six neoepitopes (C1M, p=0.012; C3A, p=0.012; C3M, p=0.0005;
      C6M, p=0.0003; CRPM, p=0.021; and VICM, p=0.046) were significantly higher in
      patients with progressive idiopathic pulmonary fibrosis (n=32) than in those with
      stable disease (n=23). In the validation cohort, mean concentrations of C1M
      (p=0.001), C3M (p=0.044), C6M (p=0.003), and CRPM (p=0.024) at baseline were
      higher in patients with idiopathic pulmonary fibrosis than in healthy controls.
      When assessed longitudinally, concentrations of six neoepitopes (BGM, C1M, C3A,
      C3M, C6M, and CRPM) were significantly higher in patients with progressive
      idiopathic pulmonary fibrosis (n=71) than in patients with stable idiopathic
      pulmonary fibrosis (n=60) by 6 months. Baseline concentrations of two neoepitopes
      were associated with increased mortality (C1M: HR 1.62 [95% CI 1.14-2.31],
      p=0.0069; C3A: 1.91 [1.06-3.46], p=0.032). The rate of change between baseline
      and 3 months of six neoepitopes (BGM: HR 1.084 [95% CI 1.03-1.14], p=0.0019; C1M:
      1.01 [1.003-1.017], p=0.0039; C3M: 1.106 [1.045-1.170], p=0.0005; C5M: 1.003
      [1.001-1.005], p=0.0011; C6M: 1.042 [1.007-1.078], p=0.017; and CRPM: 1.38 [1.16
      1.63], p=0.0002) was strongly predictive of overall survival, and the increased
      risk was proportional to the magnitude of change in neoepitope concentrations.
      The strongest association with 3-month rate of biomarker change was recorded for
      CRPM; greater than 0 ng/mL per month conferred a HR of 2.16 (95% CI 1.15-4.07),
      whereas a rate greater than 1 ng/mL per month resulted in an HR 4.08 (2.14-7.8),
      and a rate greater than 1.7 ng/mL per month was associated with an HR 6.61 (2.74
      15.94). INTERPRETATION: Concentrations of protein fragments generated by MMP
      activity are increased in the serum of individuals with idiopathic pulmonary
      fibrosis compared with healthy controls. Increased neoepitope concentrations were
      associated with disease progression, and the rate of this increase predicted
      survival. Serial measurements of neoepitopes have potential to be used as
      theragnostic biomarkers in clinical trials and to guide management of idiopathic
      pulmonary fibrosis. FUNDING: GlaxoSmithKline R&D and the Medical Research
      Council.

PMID- 25770677
TI  - Preclinical characterization of DUOC-01, a cell therapy product derived from
      banked umbilical cord blood for use as an adjuvant to umbilical cord blood
      transplantation for treatment of inherited metabolic diseases.
AB  - BACKGROUND AIMS: Cord blood (CB) transplantation slows neurodegeneration during
      certain inherited metabolic diseases. However, the number of donor cells in the
      brain of patients does not appear to be sufficient to provide benefit until
      several months after transplant. We developed the cell product DUOC-01 to provide
      therapeutic effects in the early post-transplant period. METHODS: DUOC-01
      cultures initiated from banked CB units were characterized by use of time-lapse
      photomicroscopy during the 21-day manufacturing process. Antigen expression was
      measured by means of flow cytometry and immunocytochemistry; transcripts for
      cytokines and enzymes by quantitative real-time polymerase chain reaction;
      activities of lysosomal enzymes by direct biochemical analysis; alloreactivity of
      DUOC-01 and of peripheral blood (PB) mononuclear cells (MNC) to DUOC-01 by mixed
      lymphocyte culture methods; and cytokine secretion by Bioplex assays. RESULTS:
      DUOC-01 cultures contained highly active, attached, motile, slowly proliferating
      cells that expressed common (cluster of differentiation [CD]11b, CD14 and Iba1),
      M1 type (CD16, inducible nitric oxide synthase), and M2-type (CD163, CD206)
      macrophage or microglia markers. Activities of 11 disease-relevant lysosomal
      enzymes in DUOC-01 products were similar to those of normal PB cells. All DUOC-01
      products secreted interleukin (IL)-6 and IL-10. Accumulation of transforming
      growth factor-beta, IL-1beta, interferon-gamma and TNF-alpha in supernatants was
      variable. IL-12, IL-2, IL-4, IL-5 and IL-13 were not detected at significant
      concentrations. Galactocerebrosidase, transforming growth factor-beta and IL-10
      transcripts were specifically enriched in DUOC-01 relative to CB cells. PB MNCs
      proliferated and released cytokines in response to DUOC-01. DUOC-01 did not
      proliferate in response to mismatched MNC. CONCLUSIONS: DUOC-01 has potential as
      an adjunctive cell therapy to myeloablative CB transplant for treatment of
      inherited metabolic diseases.

PMID- 25770678
TI  - Can cord blood banks transform into induced pluripotent stem cell banks?
AB  - The discovery of induced pluripotent stem cells (iPSCs) and the rapid evolution
      of clinically compliant protocols to generate such lines from a variety of tissue
      sources has raised the possibility that personalized medicine may be achievable
      in the near future. Several strategies to deliver iPSCs for iPSC-derived cell
      based therapy have been proposed: one such model has been the cell-banking model,
      using processes developed by the cord blood industry. The cord blood industry has
      evolved primarily as a banking model in which units of cord blood harvested from
      discarded placenta are stored either in a public or a private cord blood bank for
      future use. The consideration of a cord blood--like banking model has been
      further spurred by the realization that this population of cells is an ideal
      starting sample to generate pluripotent cells. Spurred by these technological
      advances, major efforts are underway to develop a current Good Manufacturing
      Practice--compliant protocol to generate iPSCs from cord blood and to develop a
      haplobanking strategy. In this article, we discuss the issues that may affect
      such an effort.

PMID- 25770679
TI  - Immunogenetic factors in the selection of cord blood units for transplantation:
      current search strategies and future perspectives.
AB  - Hematopoietic stem cell transplantation is currently used as a curative treatment
      for patients with malignant and non-malignant hematologic diseases. Human
      leukocyte antigen (HLA) matching is a major determinant for hematopoietic stem
      cell transplantation outcome. For patients lacking a fully HLA-matched donor,
      umbilical cord blood (UCB) units are alternative sources of hematopoietic stem
      cells because UCB transplantation allows a less stringent HLA matching. However,
      selection of the optimal UCB units remains challenging. The current UCB donor
      selection strategies are based on both cell dose and HLA matching. This Review
      focuses on the immunogenetic factors that influence UCB donor selection and
      highlights the future perspectives in UCB donor search. 

PMID- 25770680
TI  - Homo- and hetero-dimerization of human UDP-glucuronosyltransferase 2B7 (UGT2B7)
      wild type and its allelic variants affect zidovudine glucuronidation activity.
AB  - Most human UDP-glucuronosyltransferase (UGT; EC 2.4.1.17) genes contain non
      synonymous single nucleotide polymorphisms (nsSNPs) which cause amino acid
      substitutions. Allelic variants caused by nsSNPs may exhibit absent or reduced
      enzyme activity. UGT2B7 is one of the most important UGTs that glucuronidates
      abundant endobiotics and xenobiotics, such as estriol, morphine, and anticancer
      drugs. Three nsSNPs, UGT2B7*71S (211G>T), UGT2B7*2 (802C>T) and UGT2B7*5
      (1192G>A) are observed in the UGT2B7 gene, and they code for allozymes UGT2B7*71S
      (A71S), UGT2B7*2 (H268Y), and UGT2B7*5 (D398N). UGT2B7 has been observed to form
      oligomers that affect its enzymatic activity and in this study, we investigated
      protein-protein interactions among UGT2B7 allozymes wild type (WT), A71S, H268Y
      and D398N, by performing a systematic quantitative fluorescence resonance energy
      transfer (FRET) analysis in combination with co-immunoprecipitation assay.
      Quantitative FRET analysis revealed that UGT2B7 allozymes formed homo- and hetero
      dimers and showed distinct features in donor-acceptor distances. Both codon 71
      and codon 268 in the N-terminal domain were involved in the dimeric interaction.
      Co-immunoprecipitation experiments also proved that UGT2B7 allozymes formed
      stable dimers. The glucuronidation activities of homo- and hetero-dimers were
      further tested with zidovudine as the substrate. An increase in activity was
      observed when WT hetero-dimerized with A71S compared with homo-dimers, while both
      H268Y and D398N impaired the activity of WT and A71S by forming hetero-dimers. In
      addition, zidovudine glucuronidation activity is associated with FRET distance.
      These findings provide insights into the consequences of amino acid substitution
      in UGT2B7 on zidovudine glucuronidation and the association between protein
      protein interaction and glucuronidation activity. 

PMID- 25770681
TI  - Regulation of NAD biosynthetic enzymes modulates NAD-sensing processes to shape
      mammalian cell physiology under varying biological cues.
AB  - In addition to its role as a redox coenzyme, NAD is a substrate of various
      enzymes that split the molecule to either catalyze covalent modifications of
      target proteins or convert NAD into biologically active metabolites. The coenzyme
      bioavailability may be significantly affected by these reactions, with ensuing
      major impact on energy metabolism, cell survival, and aging. Moreover, through
      the activity of the NAD-dependent deacetylating sirtuins, NAD behaves as a beacon
      molecule that reports the cell metabolic state, and accordingly modulates
      transcriptional responses and metabolic adaptations. In this view, NAD
      biosynthesis emerges as a highly regulated process: it enables cells to preserve
      NAD homeostasis in response to significant NAD-consuming events and it can be
      modulated by various stimuli to induce, via NAD level changes, suitable NAD
      mediated metabolic responses. Here we review the current knowledge on the
      regulation of mammalian NAD biosynthesis, with focus on the relevant rate
      limiting enzymes. This article is part of a Special Issue entitled: Cofactor
      dependent proteins: evolution, chemical diversity and bio-applications. 

PMID- 25770682
TI  - Solvent and alpha-secondary kinetic isotope effects on beta-glucosidase.
AB  - beta-Glucosidase from sweet almond is a retaining, family 1, glycohydrolase. It
      is known that glycosylation of the enzyme by aryl glucosides occurs with little,
      if any, acid catalysis. For this reaction both the solvent and alpha-secondary
      kinetic isotope effects are 1.0. However, for the deglucosylation reaction (e.g.,
      kcat for 2,4-dinitrophenyl-beta-D-glucopyranoside) there is a small solvent
      deuterium isotope effect of 1.50 (+/-0.06) and an alpha-secondary kinetic isotope
      effect of 1.12 (+/-0.03). For aryl glucosides, kcat/KM is very sensitive to the
      pKa of the phenol leaving group [betalg~-1; Dale et al., Biochemistry25 (1986)
      2522-2529]. With alkyl glucosides the betalg is smaller (between -0.2 and -0.3)
      but still negative. This, coupled with the small solvent isotope effect on the pH
      independent second-order rate constant for the glucosylation of the enzyme with
      2,2,2-trifluoroethyl-beta-glucoside [D2O(kcat/KM)=1.23 (+/-0.04)] suggests that
      there is more glycone-aglycone bond fission than aglycone oxygen protonation in
      the transition state for alkyl glycoside hydrolysis. The kinetics constants for
      the partitioning (between water and various alcohols) of the glucosyl-enzyme
      intermediate, coupled with the rate constants for the forward (hydrolysis)
      reaction provide an estimate of the stability of the glucosyl-enzyme
      intermediate. This is a relatively stable species with an energy about 2 to 4
      kcal/mol higher than that of the ES complex. This article is part of a Special
      Issue entitled: Enzyme Transition States from Theory and Experiment.

PMID- 25770683
TI  - Targeting kinases in Plasmodium and Schistosoma: Same goals, different
      challenges.
AB  - With respect to parasite-induced infectious diseases of worldwide importance,
      members of the genera Plasmodium and Schistosoma are top pathogens. Nearly half a
      billion people suffer from malaria caused by Plasmodium spp. and schistosomiasis
      (bilharzia) induced by Schistosoma spp. Resistance against essentially all drugs
      used for malaria treatment has been reported. For schistosomiasis justified fear
      of upcoming resistance is discussed against the background of only one widely
      used drug for treatment. Research of the recent decade has demonstrated that
      essential steps of the biology of these and other parasites are controlled by
      kinases, which represent attractive targets for new-generation antiparasitic
      compounds. This article is part of a Special Issue entitled: Inhibitors of
      Protein Kinases. 

PMID- 25770684
TI  - A subfamily of PLP-dependent enzymes specialized in handling terminal amines.
AB  - The present review focuses on a subfamily of pyridoxal phosphate (PLP)-dependent
      enzymes, belonging to the broader fold-type I structural group and whose
      archetypes can be considered ornithine delta-transaminase and gamma-aminobutyrate
      transaminase. These proteins were originally christened "subgroup-II
      aminotransferases" (AT-II) but are very often referred to as "class-III
      aminotransferases". As names suggest, the subgroup includes mainly transaminases,
      with just a few interesting exceptions. However, at variance with most other PLP
      dependent enzymes, catalysts in this subfamily seem specialized at utilizing
      substrates whose amino function is not adjacent to a carboxylate group. AT-II
      enzymes are widespread in biology and play mostly catabolic roles. Furthermore,
      today several transaminases in this group are being used as bioorganic tools for
      the asymmetric synthesis of chiral amines. We present an overview of the
      biochemical and structural features of these enzymes, illustrating how they are
      distinctive and how they compare with those of the other fold-type I enzymes.
      This article is part of a Special Issue entitled: Cofactor-dependent proteins:
      evolution, chemical diversity and bio-applications. 

PMID- 25770685
TI  - Developing novel methods to search for substrates of protein kinases such as Rho
      kinase.
AB  - Protein phosphorylation is a major and essential post-translational modification
      in eukaryotic cells that plays a critical role in various cellular processes.
      Recent progresses in mass spectrometry techniques have enabled the effective
      identification and analysis of protein phosphorylation. Mass spectrometry-based
      approaches in investigating protein phosphorylation are very powerful and
      informative and can further improve our understanding of protein phosphorylation
      as a whole, but they cannot determine the upstream kinases involved. We introduce
      several studies that attempted to uncover the relationships between various
      kinases of interest and substrates, including two methods we developed: an in
      vitro approach termed the kinase-interacting substrate screening (KISS) method
      and an in vivo approach termed the phosphatase inhibitor and kinase inhibitor
      substrate screening (PIKISS) method. This article is part of a Special Issue
      entitled: Inhibitors of Protein Kinases. 

PMID- 25770686
TI  - Proteogenomics of the human hippocampus: The road ahead.
AB  - The hippocampus is one of the most essential components of the human brain and
      plays an important role in learning and memory. The hippocampus has drawn great
      attention from scientists and clinicians due to its clinical importance in
      diseases such as Alzheimer's disease (AD), non-AD dementia, and epilepsy.
      Understanding the function of the hippocampus and related disease mechanisms
      requires comprehensive knowledge of the orchestration of the genome, epigenome,
      transcriptome, proteome, and post-translational modifications (PTMs) of proteins.
      The past decade has seen remarkable advances in the high-throughput sequencing
      techniques that are collectively called next generation sequencing (NGS). NGS
      enables the precise analysis of gene expression profiles in cells and tissues,
      allowing powerful and more feasible integration of expression data from the gene
      level to the protein level, even allowing "-omic" level assessment of PTMs. In
      addition, improved bioinformatics algorithms coupled with NGS technology are
      finally opening a new era for scientists to discover previously unidentified and
      elusive proteins. In the present review, we will focus mainly on the proteomics
      of the human hippocampus with an emphasis on the integrated analysis of genomics,
      epigenomics, transcriptomics, and proteomics. Finally, we will discuss our
      perspectives on the potential and future of proteomics in the field of
      hippocampal biology. This article is part of a Special Issue entitled:
      Neuroproteomics: Applications in Neuroscience and Neurology. 

PMID- 25770687
TI  - APOA5 variants predispose hyperlipidemic patients to atherogenic dyslipidemia and
      subclinical atherosclerosis.
AB  - BACKGROUND: Triglycerides (TG) are the initiators of the metabolic changes
      leading to the atherogenic dyslipidemia, which is a major inducer of
      atherosclerosis as a result of quantitative and qualitative changes in
      lipoprotein subclass distributions. We hypothesized that variation at the of
      APOA5 gene locus, encoding apoAV, a key regulator of TG levels, significantly
      affect lipoprotein subclass distributions toward a more atherogenic pattern in
      both hyperTG patients and dyslipemic patients. METHODS: We recruited four hundred
      and twenty-two subjects attending a Lipid Clinic, prior to lipid-lowering
      treatment. We genotyped two APOA5 variants, rs662799 (-1131T>C) and rs3135506
      (S19W). Circulating lipoproteins were determined by nuclear magnetic resonance
      (NMR). Intima-media thickness (IMT) was evaluated using B-mode ultrasound.
      RESULTS: Carriers of the rare alleles of rs662799 and rs3135506 compared to
      common allele homozygotes, had a significantly proatherogenic profile of the VLDL
      and LDL subclasses, resulting in increased concentrations of the proatherogenic
      subclasses, large VLDLs (+133%, p<0.001) and small LDLs (+34%, p=0.014).
      Significant changes in smaller HDL (+71%, p=0.032), as well as an 18% decrease in
      large HDL (p=0.046), were also been observed. This atherogenic NMR subclass
      distribution was significantly associated with increased carotid IMT. The
      observed effects were significantly stronger in patients with a BMI>=25 kg/m2 and
      in male and female patients with a waist circumference>=90 cm or >=85 cm,
      respectively. CONCLUSION: In a dyslipemic population, genetic variants of APOA5
      modulate lipoprotein subclass distributions, inducing an atherogenic profile
      associated with IMT defined subclinical atherosclerosis.

PMID- 25770688
TI  - The PR interval and QRS duration could be predictors of renal function decline.
AB  - OBJECTIVE: Previous studies have implicated PR interval (iPR) and QRS duration
      (dQRS) obtained by electrocardiography in independent predictors of
      cardiovascular disease, which often precedes renal dysfunction. The aim of this
      study was to examine whether iPR or dQRS could be a predictor of renal function
      decline in a community-based cohort. METHODS: We enrolled 1149 healthy subjects,
      and retrospectively evaluated the relationships between iPR or dQRS and renal
      function decline, observation period of which was 3 years, and assessed whether
      iPR or dQRS could predict renal function decline. RESULTS: The iPR (r=-0.102,
      p=0.0006) or dQRS (r=-0.097, p=0.0010) was negatively associated with a rate of
      decline in estimated glomerular filtration rate (eGFR). Multiple regression
      analyses revealed that iPR (beta=-0.095, p=0.0023) or dQRS (beta=-0.069,
      p=0.0351) was an independent determinant of the rate of decline in eGFR after
      adjustment for covariates. Logistic regression analyses demonstrated that the
      longest iPR (odds ratios (OR), 2.03; 95% confidence intervals (CI), 1.49 to 2.76;
      p<0.0001) or dQRS (OR, 1.62; 95% CI, 1.16 to 2.25; p=0.0043) tertile showed an
      increased OR for prevalence of the rate of decline in eGFR<=1 ml/min/1.73 m2/year
      compared to the shortest iPR or dQRS tertile after adjustment for covariates.
      CONCLUSION: The iPR and dQRS could be independent predictors of renal function
      decline in healthy subjects.

PMID- 25770689
TI  - Association of serum total bilirubin level with severity of coronary
      atherosclerosis is linked to systemic inflammation.
AB  - OBJECTIVE: Although cardiovascular protective action of bilirubin has been
      attributed to its antioxidant effect, there was scarce data regarding the anti
      inflammatory properties. Herein, we aimed to assess the relationship between
      serum total bilirubin level and severity of coronary artery disease (CAD) in
      association with the direct inflammatory marker such as C-reactive protein (CRP),
      the other indirect markers included in inflammation process such as neutrophil to
      lymphocyte ratio (NLR) and red cell distribution width (RDW) in patients with
      stable CAD. METHODS: Angiographic data of 1501 patients were analyzed in this
      retrospective cross-sectional study. Patients were categorized according to
      Gensini scores as control, mild CAD and severe CAD groups. The association of
      clinical and laboratory parameters with the severity of CAD were determined by
      multivariable linear regression analysis. RESULTS: Total bilirubin level in the
      control group was significantly higher than those of the other groups. After
      multivariable linear regression analysis total bilirubin [beta=-3.131 (-4.481, 
      1.782), p<0.001] was significantly associated with the severity of CAD.
      Futhermore, there was a moderate and significant inverse correlation between
      serum total bilirubin level and the severity of CAD (r=-0.173, p<0.001), CRP (r=
      0.112, p<0.001), NLR (r=-0.070, p=0.026) and RDW (r=-0.074, p=0.027). CONCLUSION:
      Serum total bilirubin level was independently and inversely associated with the
      severity of coronary atherosclerosis in patients with stable CAD. In addition,
      total bilirubin level was inversely correlated with CRP, NLR and RDW. These
      results suggest that besides its already known effect on the oxidative stress,
      higher serum total bilirubin level may exhibit an anti-inflammatory effect in the
      coronary atherosclerotic process.

PMID- 25770690
TI  - Glycated hemoglobin and long-term prognosis in patients with suspected stable
      angina pectoris without diabetes mellitus: a prospective cohort study.
AB  - OBJECTIVE: Associations of glycated hemoglobin A1c (HbA1c) levels to incident
      coronary and cardiovascular events among non-diabetic patients with coronary
      artery disease are unclear. We investigated relations of HbA1c to long-term
      prognosis in such patients. METHODS: A prospective cohort of 2519 patients
      undergoing elective coronary angiography for suspected stable angina pectoris
      (SAP) was divided into pre-defined categories according to HbA1c (%) levels
      (<5.0, 5.0-5.6 (reference), 5.7-6.4), and followed for median 4.9 years. The
      primary end-point was major coronary events (including non-fatal and fatal acute
      myocardial infarctions, and sudden cardiac death). Secondary end-points were
      death from cardiovascular disease (CVD) and all-cause mortality. Hazard ratios
      (HRs) (95% confidence intervals [CIs]) were obtained by Cox regression. RESULTS:
      Median age at inclusion was 62 years, 73% were males, median HbA1c was 5.6% and
      random plasma-glucose 5.4 mmol/L. After multivariate adjustment, HbA1c levels
      within the pre-diabetic range were not associated with risk of major coronary
      events, HR (95% CI): 1.13 (0.79-1.62); P=0.49, death from CVD or all-cause
      mortality HR (95% CI): 0.95 (0.55-1.66) and 1.04 (0.70-1.53), respectively;
      P>=0.85. Similarly, there was no significant association between HbA1c values
      within the lowest category and risk of study outcomes, (P>=0.18). CONCLUSION: In
      non-diabetic patients with suspected SAP, there was no overall association
      between HbA1c levels and prognosis, questioning an independent role of glycemia
      in the pathogenesis of atherosclerotic complications in these patients.

PMID- 25770691
TI  - pXO16 from Bacillus thuringiensis serovar israelensis: Almost 350 kb of terra
      incognita.
AB  - Bacillus thuringiensis strains usually harbor large sets of plasmids, some of
      which carrying the entomopathogenic delta-endotoxins. B. thuringiensis serovar
      israelensis, active on Dipteran larvae, carries the very large conjugative
      plasmid pXO16 (350 kb). pXO16 displays a macroscopic aggregation phenotype when
      liquid cultures of conjugative partners are mixed. Its conjugative apparatus is
      able of transferring itself and other non-conjugative and non-mobilizable
      plasmids in a fast and very efficient manner. Even though its conjugative
      kinetics and capabilities have been extensively studied, the genetic bases for
      this unique transfer system remain largely unknown. In this work, the sequence of
      pXO16 has been identified in the existing sequenced genome of B. thuringiensis
      sv. israelensis HD-789 as corresponding to the p01 plasmid. Despite pXO16
      sequence being highly coding, few CDS possess homologs in the databases. However,
      potential regions responsible for the aggregation phenotype and the plasmid
      replication have been highlighted. The common orientation of all CDS and the
      presence of a high number of potential paralogs suggested a phage-like nature.
      Concerning conjugative functions, no significant type IV secretion system
      homologs have been found, indicating that pXO16 encodes an unforeseen conjugative
      system.

PMID- 25770692
TI  - Potential of vitamin D in treating diabetic cardiomyopathy.
AB  - Cardiovascular disease is the leading cause of morbidity and mortality in
      patients with diabetes mellitus (DM), and patients with DM frequently develop
      diabetic cardiomyopathy. Currently, effective treatments for diabetic
      cardiomyopathy are limited. Vitamin D exerts pleiotropic effects on the
      cardiovascular system and is associated with DM. The purpose of this review was
      to evaluate published research on vitamin D in diabetic cardiomyopathy by
      searching PubMed databases. Herein, we reviewed vitamin D metabolism; evaluated
      the molecular, cellular, and neuroendocrine effects in native and bioactive
      vitamin D; and evaluated the role of vitamin D in treating cardiovascular disease
      and DM. Some evidence suggests that vitamin D may improve cardiovascular outcomes
      in diabetes through anti-inflammatory, antioxidative, antihypertrophic,
      antifibrotic, and antiatherosclerotic activities and by regulating advanced
      glycation end-product signaling, the renin-angiotensin system, and cardiac
      metabolism. This clinical and laboratory evidence suggests that vitamin D may be
      a potential agent in treating diabetic cardiomyopathy. However, using vitamin D
      entails possible adverse risks of hypercalcemia, hyperphosphatemia, and vascular
      calcifications. Therefore, future studies should be conducted that clarify the
      potential benefits of vitamin D through large-scale randomized clinical trials in
      well-defined groups of diabetic patients. 

PMID- 25770693
TI  - Darkening mechanism and kinetics of humification process in catechol-Maillard
      system.
AB  - Humic acids, products of humification process, are capable of interacting with
      contaminants and can be applied to environmental remediation. Browning mechanisms
      of humification is critical to understand and further control the process. This
      study aimed to investigate the mechanism of abiotic humification by tracking the
      fate of the precursors in systems containing glucose, glycine, and various CT
      concentrations, which were promoted by MnO2. Results show that the N-containing
      organic molecules significantly contributed in controlling the darkening effect.
      Increasing CT promoted the formation of Fulvic-like acids (FLAs) and Humic-like
      acids (HLAs). The entire reaction could be divided into two steps following
      pseudo-second-order kinetics equation and pseudo-zero-order kinetics equation.
      Moreover, increasing CT contributed to the increase of the degree of unsaturation
      in HLAs.

PMID- 25770694
TI  - Cytotoxicity of ZnO NPs towards fresh water algae Scenedesmus obliquus at low
      exposure concentrations in UV-C, visible and dark conditions.
AB  - Continuous increase in the usage of ZnO nanoparticles in commercial products has
      exacerbated the risk of release of these particles into the aquatic environment
      with possible harmful effects on the biota. In the current study, cytotoxic
      effects of two types of ZnO nanoparticles, having different initial effective
      diameters in filtered and sterilized lake water medium [487.5+/-2.55 nm for ZnO-1
      NPs and 616.2+/-38.5 nm for ZnO-2 NPs] were evaluated towards a dominant
      freshwater algal isolate Scenedesmus obliquus in UV-C, visible and dark
      conditions at three exposure concentrations: 0.25, 0.5 and 1 mg/L. The toxic
      effects were found to be strongly dependent on the initial hydrodynamic particle
      size in the medium, the exposure concentrations and the irradiation conditions.
      The loss in viability, LDH release and ROS generation were significantly enhanced
      in the case of the smaller sized ZnO-1 NPs than in the case of ZnO-2 NPs under
      comparable test conditions. The toxicity of both types of ZnO NPs was
      considerably elevated under UV-C irradiation in comparison to that in dark and
      visible light conditions, the effects being more enhanced in case of ZnO-1 NPs.
      The size dependent dissolution of the ZnO NPs in the test medium and possible
      toxicity due to the released Zn(2+) ions was also noted. The surface adsorption
      of the nanoparticles was substantiated by scanning electron microscopy. The
      internalization/uptake of the NPs by the algal cells was confirmed by
      fluorescence microscopy, transmission electron microscopy, and elemental
      analyses.

PMID- 25770695
TI  - Treating substance abuse is not enough: comorbidities in consecutively admitted
      female prisoners.
AB  - INTRODUCTION: Several studies have pointed to high rates of substance use
      disorders among female prisoners. The present study aimed to assess comorbidities
      of substance use disorders with other mental disorders in female prisoners at
      admission to a penal justice system. METHODS: A sample of 150 female prisoners,
      consecutively admitted to the penal justice system of Berlin, Germany, was
      interviewed using the Mini-International Neuropsychiatric Interview (MINI). The
      presence of borderline personality disorder was assessed using the Structured
      Clinical Interview II for DSM-IV. Prevalence rates and comorbidities were
      calculated as percentage values and 95% confidence intervals (CIs). RESULTS:
      Ninety-three prisoners (62%; 95% CI: 54-70) had substance use disorders; n=49
      (33%; 95% CI: 24-42) had alcohol abuse/dependence; n=76 (51%; 95% CI: 43-59) had
      illicit drug abuse/dependence; and n=53 (35%; 95% CI: 28-44) had opiate use
      disorders. In the group of inmates with substance use disorders, 84 (90%) had at
      least one other mental disorder; n=63 (68%) had comorbid affective disorders;
      n=45 (49%) had borderline or antisocial personality disorders; and n=41 (44%) had
      comorbid anxiety disorders. CONCLUSIONS: Female prisoners with addiction have
      high rates of comorbid mental disorders at admission to the penal justice system,
      ranging from affective to personality and anxiety disorders. Generic and robust
      interventions that can address different comorbid mental health problems in a
      flexible manner may be required to tackle widespread addiction and improve mental
      health of female prisoners.

PMID- 25770696
TI  - The impact opportunity.

PMID- 25770697
TI  - Large ileocecal submucosal lipoma presenting as hematochezia, a case report and
      review of literature.
AB  - INTRODUCTION: Colonic lipomas are rare subepithelial benign tumors affecting
      mainly middle-aged women. They are usually asymptomatic and, hence, are
      discovered incidentally on autopsy, surgery, or colonoscopy. There is a wide
      range of presentations like abdominal pain, bleeding per rectum, intussusception,
      etc. The latter picture constitutes the usual presentation of an ileocecal
      lipoma. Only few cases of ileocecal lipomas presenting as lower GI bleeding have
      been reported in the literature. PRESENTATION OF CASE: We present a case of an
      adult female patient who was admitted to our institution complaining of
      hematochezia and right lower quadrant pain. She was found to have chronic anemia.
      She was investigated by CT scan of the abdomen & pelvis and by colonoscopy which
      showed a fungating, submucosal mass with ulcerated base near the ileocecal valve.
      She underwent a colonic resection. The pathology came out as a submucosal benign
      pedunculated ileocecal lipoma. DISCUSSION: Colonic lipomas represent 4% of benign
      lesions of the gastrointestinal tract. They are usually asymptomatic hence are
      often discovered incidentally on colonoscopy, surgery or autopsy. The definitive
      diagnosis is made by pathological evaluation. Colonic lipomas are usually treated
      if they are symptomatic or there is any suspicion of malignancy. The treatment
      modalities include endoscopic and surgical resection. CONCLUSION: We, hereby,
      describe a case of benign ileocecal lipoma that presented with hematochezia which
      is an unusual presentation. Also, there is a great controversy regarding the
      treatment of colonic lipomas. In this article, we tried to answer several
      questions concerning the management of ileocecal lipomas.

PMID- 25770698
TI  - Sclerosing mediastinitis of unknown origin: Report of a case.
AB  - INTRODUCTION: We herein describe a rare case of a sclerosing mediastinitis
      without IgG4-related disease. This case was clearly excluded from IgG4-related
      disease, because this patient's serum IgG4 level was not elevated. Specifically,
      this patient's serum IgG4 level was 7.9mg/dl (4.8-105). PRESENTATION OF CASE: A
      61-year-old Japanese female presented at our hospital due to an abnormal chest X
      ray that showed a growing shadow in the mediastinum. Chest computed tomography
      (CT) showed an 80*75*75mm tumor, which located in the anterior mediastinum. This
      large tumor surrounded the thoracic aorta, left brachiocephalic vein and superior
      vena cava. It was difficult to obtain a definitive diagnosis. We tried to perform
      three biopsies, and eventually performed a partial resection of the tumor.
      DISCUSSION: This case did not fit the criteria for IgG4-related disease, and it
      was therefore unclear whether steroid therapy should be used for this case. We
      will continue to carefully follow up this patient's residual lesion, and there
      have been no changes in the lesion at present. CONCLUSION: Sclerosing
      mediastinitis and IgG4-related disease should be included in the differential
      diagnosis of patients presenting with a mediastinal tumor. However, sclerosing
      mediastinitis is difficult to diagnose, and it is important to obtain a
      sufficient amount of tissue to ensure an accurate diagnosis.

PMID- 25770700
TI  - Eating a meal is associated with elevations in agreeableness and reductions in
      dominance and submissiveness.
AB  - Many studies have shown that having a meal together with others increases food
      intake. In contrast, the effects of having a meal on interactions with others
      have rarely been examined. More specifically, it is unknown if having a social
      interaction during a meal alters how people feel, behave, and perceive others. In
      the present study, 98 working individuals provided information on their everyday
      social interactions over a three-week period by filling in a form soon after each
      interaction. Record forms included items representing mood state, interpersonal
      behaviors, and perceptions of interaction partners. Participants also indicated
      whether interactions took place during a meal. Engaging in an interaction that
      involved eating a meal was associated with decreased alertness and, particularly
      in women, with increased pleasant affect, compared to interactions that did not
      involve eating a meal. Independently of this, during a meal participants reported
      fewer dominant and submissive behaviors and more agreeable behaviors, and also
      perceived interaction partners as more agreeable. These results were largely
      independent of contextual factors such as the gender and role of the primary
      social interaction partner, the presence of multiple partners, and the location
      of the interaction. Overall, social interactions during a meal were more positive
      in terms of how people felt, behaved, and perceived others. At the same time,
      agentic behaviors were reduced. These results suggest that shared meals are
      events in which affiliative bonds are strengthened in the context of weakened
      displays of hierarchy. 

PMID- 25770699
TI  - A potential role for the acid-sensing T cell death associated gene-8 (TDAG8)
      receptor in depression-like behavior.
AB  - Inflammation has been suggested to contribute to the pathophysiology of
      depression. The T cell death associated gene-8 (TDAG8) receptor is a proton
      sensing G-protein-coupled receptor (GPCR) expressed on immune cells in both the
      CNS and periphery. Previous work has shown modulation of inflammation by the
      TDAG8 receptor, with pro-inflammatory responses reported in the central nervous
      system (CNS). Given the link between depression and inflammation, the aim of the
      present study was to investigate the role of TDAG8 in depression relevant
      behaviors. Mice deficient in TDAG8 (TDAG8(-/-)) were tested in the forced swim
      test (FST) and sucrose preference paradigm. TDAG8 deficiency resulted in
      significant attenuation of immobility in the FST as compared to wild type TDAG8
      (TDAG8(+/+)) mice. These differences were not due to alterations in motor
      activity evoked by TDAG8 deficiency as TDAG8(+/+) and TDAG8(-/-) mice displayed
      similar activity in the home cage or in a novel context. TDAG8(-/-) mice showed
      significantly higher consumption of sucrose compared to wild type mice although
      sucrose preference was not significantly different between genotypes.
      Collectively, our results support the involvement of the TDAG8 receptor in
      behavioral response relevant to depression. Further investigation is required to
      validate TDAG8 as a novel target linking inflammation and depression. 

PMID- 25770701
TI  - A new function of rapid eye movement sleep: improvement of muscular efficiency.
AB  - Previously I demonstrated that the slow wave sleep (SWS) functioned to adjust the
      emotional balance disrupted by emotional memories randomly accumulated during
      waking, while the rapid eye movement (REM) sleep played the opposite role. Many
      experimental results have unambiguously shown that various emotional memories are
      processed during REM sleep. In this article, it is attempted to combine this
      confirmed function of REM sleep with the atonic state unique to REM sleep, and to
      integrate a new theory suggesting that improvement of muscular efficiency be a
      new function of REM sleep. This new function of REM sleep is more advantageous
      than the function of REM sleep in emotional memories and disinhibited drives to
      account for the phylogenetic variations of REM sleep, especially the absence of
      REM sleep in dolphins and short duration of REM sleep in birds in contrary to
      that in humans and rodents, the absence of penile erections in REM sleep in
      armadillo, as well as the higher voltage in EEG during REM sleep in platypus and
      ostrich. Besides, this new function of REM sleep is also advantageous to explain
      the association of REM sleep with the atonic episodes in SWS, the absence of
      drastic menopausal change in duration of REM sleep, and the effects of ambient
      temperature on the duration of REM sleep. These comparative and experimental
      evidences support the improvement of muscular efficiency as a new and major
      function of REM sleep. 

PMID- 25770702
TI  - Engineering electrodes for microbial electrocatalysis.
AB  - Microbial electrocatalysis refers to the use of microorganisms to catalyze
      electrode reactions. Many processes have been developed on this principle,
      ranging from power generation to CO2 conversion using bioelectrochemical systems.
      The nature of the interface between the microorganisms and the electrodes
      determines the functioning and efficiency of these systems. This interface can be
      manipulated in terms of chemical and topographical features to better understand
      the interaction at nanometer and micrometer scales. Here we discuss how the
      electrode surface topography and chemistry impact the microorganism-electrode
      interaction both for direct and indirect electron transfer mechanisms. It appears
      that composite materials that combine high conductivity with excellent
      biocompatibility are most attractive towards application. In most cases this
      implies a combination of a metallic backbone with a carbon coating with a defined
      topography and chemistry. 

PMID- 25770703
TI  - Isolation rearing impaired sensorimotor gating but increased pro-inflammatory
      cytokines and disrupted metabolic parameters in both sexes of rats.
AB  - Social isolation rearing (SIR) is an early stress paradigm of deprivation of the
      social contact since weaning. SIR has been used to investigate the mechanisms
      behind certain mental illnesses with neurodevelopmental origins, including
      schizophrenia. In schizophrenia, metabolic dysfunction has become a critical
      issue with increasing evidence for a possible connection between metabolism and
      immune systems in which metabolic changes are associated with pro-inflammatory
      cytokine (pro-CK) levels. The present study employed a rat model of SIR with both
      sexes to examine behaviors [locomotor activity and prepulse inhibition (PPI)],
      inflammatory markers [C-reactive protein, interleukin (IL)-1 beta, IL-6, IL-10,
      tumor necrosis factor (TNF)-alpha and interferon-gamma], and metabolism-related
      variables (body weight, blood pressure, and the profiles of glycemia and lipid).
      Our results revealed that around puberty, SIR rats of both sexes exhibited
      behaviorally a higher locomotor activity and a lower PPI performance.
      Biochemically, SIR rats had an elevated level of pro-CKs (IL-1 beta, IL-6, TNF
      alpha, and interferon-gamma), and metabolic abnormalities (increased insulin
      resistance, decreased insulin sensitivity, and high blood pressure) in a time
      dependent manner. The relationships between pro-CKs and metabolism were sex
      specific as IL-1 beta and interferon-gamma were correlated to glycemia metabolic
      indexes in males. The present study demonstrated SIR-induced longitudinal
      concomitant changes of pro-CKs and metabolic abnormalities, implying a more
      direct role of these two things in mental dysfunctions with a developmental
      origin. 

PMID- 25770706
TI  - Recent Advances in Autoimmune Pancreatitis.
AB  - Autoimmune pancreatitis (AIP) is a form of chronic pancreatitis that is
      characterized clinically by frequent presentation with obstructive jaundice,
      histologically by a dense lymphoplasmacytic infiltrate with fibrosis, and
      therapeutically by a dramatic response to corticosteroid therapy. Two distinct
      diseases, type 1 and type 2 AIP, share these features. However, these 2 diseases
      have unique pancreatic histopathologic patterns and differ significantly in their
      demographic profiles, clinical presentation, and natural history. Recognizing the
      popular and long-standing association of the term "AIP" with what is now called
      "type 1 AIP," we suggest using "AIP" solely for type 1 AIP and to acknowledge its
      own distinct disease status by using "idiopathic duct-centric chronic
      pancreatitis" (IDCP) for type 2 AIP. AIP is the pancreatic manifestation of
      immunoglobulin G4-related disease (IgG4-RD). The etiopathogenesis of AIP and IgG4
      RD is largely unknown. However, the remarkable effectiveness of B-cell depletion
      therapy with rituximab in patients with AIP and IgG4-RD highlights the crucial
      role of B cells in its pathogenesis. IDCP is less commonly recognized, and little
      is known about its pathogenesis. IDCP has no biomarker but is associated with
      inflammatory bowel disease in ~25% of patients. Recently, the international
      consensus diagnostic criteria for AIP identified combinations of features that
      are diagnostic of both diseases. Both AIP and IDCP are corticosteroid responsive;
      however, relapses are common in AIP and rare in IDCP. Therefore, maintenance
      therapy with either an immunomodulator (eg, azathioprine, 6-mercaptopurine, or
      mycophenolate mofetil) or rituximab is often necessary for patients with AIP.
      Long-term survival is excellent for both patients with AIP and patients with
      IDCP.

PMID- 25770705
TI  - Reconstruction of optical scanned images of inhomogeneities in biological tissues
      by Monte Carlo simulation.
AB  - The optical imaging of inhomogeneities located in phantoms of biological tissues,
      prepared from goat's isolated heart as control tissue and embedded with spleen
      and adipose tissues representing tumors, by Monte Carlo simulation, is carried
      out. The proposed scanning probe consists of nine units. Each unit is equipped
      with one photon injection port and three ports arranged in a straight line to
      collect backscattered photons emerging from various depths, and one port, placed
      coaxially to the source on the opposite side of the phantom, to collect the
      transmitted component. At each position of the grid, superposed on the tissue
      phantom, photons are introduced through source port into the phantoms and
      backscattered and transmitted photons are collected by respective ports. Based on
      the data collected from the entire grid surface the respective gray-level images
      are reconstructed. The inhomogeneity located at certain depth (2, 4, 6mm) is
      visualized in three images formed by the backscattered data collected by three
      ports. Increase or decrease in normalized backscattered intensity (NBI) observed
      in their scans corresponds to that of high scattering (adipose) or absorbing
      (spleen) inhomogeneity compared to that of control tissue and also their location
      as determined by NBI variation as received at various ports. The images
      constructed from the transmitted data are associated with decrease in intensity.
      The scans of these images through their centers show that normalized transmitted
      intensity (NTI) attains its maximum value when the inhomogeneities are at depth
      6mm. These scans are of higher amplitude for spleen compared to that of adipose
      tissues. Thus the data received by backscattering and transmission complement
      each other in identifying the location and type of inhomogeneities.

PMID- 25770707
TI  - Validation of Clinical Indicators of Imbalanced Nutrition: Less Than Body
      Requirements in Early Childhood.
AB  - This is a clinical validation study of the nursing diagnosis of imbalanced
      nutrition: less than body requirements based on the diagnostic accuracy measures.
      Measures of sensitivity and specificity were calculated based on the latent class
      analysis method using a random effects model in a sample of 123 children between
      0 and 6 years old. The prevalence of the diagnosis was estimated to be 27.6%
      using the latent class model. Indicators that exhibited the best measures of
      diagnostic accuracy included insufficient interest in food and satiety
      immediately upon ingesting food. A total of seven clinical indicators were
      validated clinically.

PMID- 25770708
TI  - Catering for vulnerable populations: customised care.

PMID- 25770709
TI  - Erratum: Back to Back column in our December 2014 issue - correction to
      reference.

PMID- 25770704
TI  - Improved sleep quality in older adults with insomnia reduces biomarkers of
      disease risk: pilot results from a randomized controlled comparative efficacy
      trial.
AB  - IMPORTANCE: Sleep disturbances have been linked to increased morbidity and
      mortality, yet it is unknown whether improving sleep quality in older adult
      patients with insomnia alters biomarkers of diabetes and cardiovascular disease
      risk. OBJECTIVE: Determine the comparative efficacy of cognitive behavioral
      therapy (CBT), tai chi chih (TCC), and a sleep seminar control (SS) to reduce
      multisystem biomarkers of disease risk in older adults with insomnia. DESIGN:
      Randomized controlled comparative efficacy trial. SETTING: Los Angeles community.
      PARTICIPANTS: A population-based sample of 109 older adults with chronic and
      primary insomnia. INTERVENTION: Random assignment to CBT, TCC, or SS for 2-h
      group sessions weekly over 4 months with a 16-month evaluation (1 year after
      follow-up). MAIN OUTCOME(S) AND MEASURE(S): Multisystem biological risk comprised
      of 8 biomarkers: high-density lipoprotein, low-density lipoprotein,
      triglycerides, hemoglobinA1c, glucose, insulin, C-reactive protein, and
      fibrinogen. Using clinical laboratory cutoffs defined as abnormal, a multisystem
      risk score was computed representing a sum of the deviation around the cutoffs
      across the 8 biomarkers. In addition, high risk grouping was classified if
      subjects exhibited 4 or more biomarkers in the abnormal laboratory range.
      RESULTS: An interaction of time-by-treatment-by-high risk group was found (F(4,
      197.2)=3.14, p=.02) in which both TCC (p=.04) and CBT (p=.001) showed
      significantly lower risk scores as compared to SS at 16-months. CBT reduced risk
      of being in the high risk group at 4-months (odds ratio [OR]=.21 [95% CI, .03
      1.47], p<.10) and at 16-months (OR=.06 [95% CI, .005-.669]; p<.01). TCC reduced
      the risk at 16-months (OR=.10 [95% CI, .008-1.29]; p<.05) but not at 4 months. Of
      participants who were classified in the high risk category at baseline,
      improvements in sleep quality, as defined by a clinical severity threshold,
      reduced the likelihood of being in the high risk group at 16-months, OR=.08 (95%
      CI, .008-.78); p=.01. CONCLUSIONS AND RELEVANCE: Participants classified as
      having high multisystem biological risk at entry and assigned to CBT or TCC show
      improvements in risk scores after one year follow-up. Given that these clinical
      biomarkers are associated with cardiovascular, metabolic, and inflammatory
      disease risk, improving sleep quality has the potential to reduce the risk of
      chronic disease in older adults with insomnia. Clinical Trial Registration # and
      name-ClinicalTrials.gov: NCT00280020, Behavioral Treatment of Insomnia in Aging

PMID- 25770710
TI  - International perspective: reducing hearing loss.

PMID- 25770711
TI  - Estimated prevalence of hearing loss and provision of hearing services in Pacific
      Island nations.
AB  - INTRODUCTION: Hearing impairment (HI) affects an estimated 538 million people
      worldwide, with 80% of these living in developing countries. Untreated HI in
      childhood may lead to developmental delay and in adults results in social
      isolation, inability to find or maintain employment, and dependency. Early
      intervention and support programmes can significantly reduce the negative effects
      of HI. AIM: To estimate HI prevalence and identify available hearing services in
      some Pacific countries - Cook Islands, Fiji, Niue, Samoa, Tokelau, Tonga.
      METHODS: Data were collected through literature review and correspondence with
      service providers. Prevalence estimates were based on census data and previously
      published regional estimates. RESULTS: Estimates indicate 20-23% of the
      population may have at least a mild HI, with up to 11% having a moderate
      impairment or worse. Estimated incidence of chronic otitis media in Pacific
      Island nations is 3-5 times greater than other Australasian countries in children
      under 10 years old. Permanent HI from otitis media is substantially more likely
      in children and adults in Pacific Island nations. Several organisations and
      individuals provide some limited hearing services in a few Pacific Island
      nations, but the majority of people with HI are largely underserved. DISCUSSION:
      Although accurate information on HI prevalence is lacking, prevalence estimates
      of HI and ear disease suggest they are significant health conditions in Pacific
      Island nations. There is relatively little support for people with HI or ear
      disease in the Pacific region. An investment in initiatives to both identify and
      support people with hearing loss in the Pacific is necessary.

PMID- 25770712
TI  - Who attends Dunedin's free clinic? A study of patients facing cost barriers to
      primary health care access.
AB  - INTRODUCTION: Several methods of reducing the cost barrier to primary health care
      have been implemented in New Zealand, but research about free primary health care
      and the patients who use such services is scarce. AIM: To compare the
      characteristics of patients at Dunedin's free clinic with those at a traditional
      general practice clinic. METHODS: A written survey was distributed to waiting
      room patients at the Free Clinic and a fee-charging clinic in close proximity.
      Patient records were accessed to determine health services utilisation rates at
      both clinics and the discounting rate at the traditional clinic. RESULTS: There
      were 126 patient surveys returned at the Traditional Clinic and 65 at the Free
      Clinic. There was a significantly greater proportion of Maori respondents at the
      Free Clinic than at the Traditional Clinic (24.1% versus 9.2%, p=0.011). The
      difference in deprivation profiles of Free Clinic and Traditional Clinic
      respondents was more marked for the individual deprivation measure (five or more
      NZiDep deprivation characteristics: 65.5% versus 13.3%, p<0.001) than for
      residential area deprivation (NZDep2006 quintile 5: 41.4% versus 15.8%, p<0.001).
      Emergency department presentation rates were high for Free Clinic patients,
      despite free primary care access and high general practitioner consultation
      rates. Among Traditional Clinic respondents, 31.7% reported deferring health care
      because of cost in the previous 12 months. The equivalent figure for Free Clinic
      respondents was 63.8%. DISCUSSION: This survey suggests that Dunedin's Free
      Clinic serves a vulnerable population, in whom levels of unmet health need and
      health service usage are high.

PMID- 25770713
TI  - The effect of ethnicity on different ways of expressing cardiovascular treatment
      benefits and patient decision-making.
AB  - INTRODUCTION: The way information is presented to communicate risk and treatment
      benefit affects patients' understanding and perception of their risk and can
      influence their decisions. AIM: To assess the effect of ethnicity on patient
      preferences for different ways of expressing risk and treatment benefits.
      METHODS: Using tailored questionnaires, we surveyed Ma-ori , Pacific and Indian
      peoples of known CVD risk to assess format preferences encouraging them to take
      medication or assist their understanding of possible treatment benefits.
      Statistical analysis determined any association of ethnicity with patient
      preferences. RESULTS: Of the 376 participants, 50% identified as New Zealand (NZ)
      European; 15% Maori ; 25% Pacific and 10% Indian ethnicity. Patients preferred
      positive framing of risk (66%). Relative risk was the format reported as most
      encouraging to take medication and to understand risk, with natural frequencies
      least preferable, although Pacific people significantly preferred natural
      frequencies (p<0.0001) compared with other ethnic groups. The majority (55%)
      preferred pictures to numbers for explaining risk. Ma-ori , Pacific and Indian
      participants significantly preferred 100-people chart formats over bar graphs
      compared with NZ Europeans/Others (p=0.002). Most (68%) preferred doctors to give
      their opinion on taking medication instead of explaining risks using numbers
      and/or pictures. Pacific and Indian peoples significantly preferred doctors to
      make decisions on treatment compared to NZ European/Other and Ma-ori participants
      (p<0.0001). DISCUSSION: Ethnic differences in patient preferences for
      communication formats and decision-making should be considered when tailoring
      effective communication in primary care. However, individual preferences cannot
      be presumed and a combination of methods should routinely be used.

PMID- 25770714
TI  - Nurses' reported use of standing orders in primary health care settings.
AB  - INTRODUCTION: The Medicines (Standing Order) Amendment Regulations 2011 allow
      medicines to be supplied or administered to a patient by a nurse in the absence
      of a medical practitioner and without a prescription. Regulations have been in
      place since 2002, but no substantive research has occurred in New Zealand
      concerning their use. AIM: This paper reports a survey of registered nurses (RNs)
      who work in primary health care (PHC) settings and explores aspects of their
      practice relating to their use of standing orders. METHODS: A self-reported
      survey using a non-probability sample of RNs working in PHC who use standing
      orders in their practice (n=231). Data were analysed descriptively. RESULTS: The
      sample were experienced RNs (mean 24 years since registration) and 53% have a
      postgraduate qualification. Some nurses' understanding of a standing order
      included provision of a prescription to a patient. Standing orders were used
      frequently (42% reported use 1 to >5 times/day) for a wide variety of conditions.
      There is a significant relationship between undertaking the stated professional
      development requirements and confidence in the clinical decisions made (p=0.025).
      Over half (52%) would like to use standing orders more often. DISCUSSION:
      Standing orders are used extensively in PHC settings. The conditions nurses are
      involved in treating are usually already differentiated or have a high degree of
      diagnostic certainty. Nurses can effectively provide medicines under standing
      orders when doctors support their use, issue evidence-based orders, and have
      confidence in nurses with advanced skills. Doctors need to meet their
      responsibilities under the Regulations.

PMID- 25770715
TI  - Management of diabetes by primary health care nurses in Auckland, New Zealand.
AB  - INTRODUCTION: The increasing prevalence of diabetes has led to expanded roles for
      primary health care nurses in diabetes management. AIM: To describe and compare
      anthropometric and glycaemic characteristics of patients with diabetes and their
      management by practice nurses, district nurses and specialist nurses. METHODS:
      Primary health care nurses in Auckland randomly sampled in a cross-sectional
      survey, completed a postal self-administered questionnaire (n=284) and telephone
      interview (n=287) between 2006 and 2008. Biographical and diabetes management
      details were collected for 265 (86%) of the total 308 patients with diabetes seen
      by participants on a randomly selected day. RESULTS: Nurses were able to access
      key clinical information for only a proportion of their patients: weight for 68%;
      BMI for 16%; HbA1c for 76% and serum glucose levels for 34% (for either measure
      82%); although most (96%) records were available about whether patients self
      monitored blood glucose levels. Most nursing management activities focused on
      giving advice on dietary intake (70%) and physical activity (66%), weighing
      patients (58%), and testing or discussing blood glucose levels (42% and 43%,
      respectively). These proportions varied by nurse group (p<0.05), generally being
      highest for specialist nurses and lowest for district nurses. DISCUSSION: Most
      practice and specialist nurses could access patients' weight and HbA1c levels and
      focused their clinical management on health education to decrease these if
      indicated. Communication and organisational systems and contracts that allow
      district nurses to work across both primary and secondary health services are
      necessary to improve community-based nursing services for patients with diabetes.

PMID- 25770716
TI  - 'He said he had been out doing the traffic': general practitioner perceptions of
      sexually transmitted infection and HIV testing strategies for men.
AB  - INTRODUCTION: Sexual health is an important component of primary care, and
      optimal sexually transmitted infection (STI) and HIV testing by doctors could
      help improve sexual health outcomes for men. Currently, little is known about
      general practitioners' (GPs') assessment of STI and HIV risk, particularly in
      relation to male patients, and the degree to which current advice can be
      translated into consistent testing protocols. The aim of the study was to explore
      STI and HIV testing strategies for men in general practice and opportunities and
      barriers to more optimal testing. METHODS: This study used a qualitative,
      multiple-case methodology, incorporating 17 distinct GP cases, drawing on in
      depth, semi-structured interviews, and using thematic analysis. FINDINGS: The
      following themes were identified: sexual health consultations by men in general
      practice are usually initiated by the patient; GPs appear to have a consistent
      rationale for their risk assessments in terms of STI testing; the nature of the
      doctor's interaction with men influences the quality of sexual health services
      utilisation; optimal sexual health consultations require sufficient time and a
      recognition of the 'delicacy' of the consultation content for both patient and
      health practitioner. CONCLUSION: The stratified testing strategies undertaken by
      GPs appeared appropriate given the risk profiles of their patients. Constraints
      to optimal sexual health consultations were identified, including inadequate
      consultation time, male utilisation of GP consultations, and challenges in
      discussing sexual health topics within the consultation. Prioritising men's
      sexual health as a topic in CME may be helpful.

PMID- 25770717
TI  - Feasibility of an after-school group-based exercise and lifestyle programme to
      improve cardiorespiratory fitness and health in less-active Pacific and Maori
      adolescents.
AB  - INTRODUCTION: Obesity and low levels of physical activity are increasing among
      Pacific and Maori adolescents in New Zealand. AIM: To assess the feasibility of
      an after-school exercise and lifestyle programme to improve cardiorespiratory
      fitness, health and usual activity in less-active Pacific and Maori adolescents
      over six weeks. METHODS: Eighteen less-active secondary school students
      participated. The six-week programme included 3 x 1.5 hour exercise and healthy
      lifestyle sessions per week. Outcomes included estimated cardiorespiratory
      fitness (VO2max), insulin resistance (Homeostasis Model Assessment), physical
      activity, glycated haemoglobin (HbA1c), fasting plasma glucose, blood pressure,
      waist circumference and fasting lipids, measured at baseline and six weeks.
      Programme attendance and qualitative comments were also recorded. Student's t
      tests were used. RESULTS: Of the 18 students enrolled, 16 (89%) completed six
      week follow-up, 14 (78%) were female, 13 (72%) were Pacific ethnicity and 5 (28%)
      were Maori . At baseline, mean age was 16.3 (standard deviation [SD] 1.0) years,
      body mass index (BMI) 35.2 (SD 6.7) kg/m2, VO2max 31.5 (SD 4.3) mL/kg/min,
      systolic blood pressure 125.0 (SD 12.9) mm Hg, HbA1c 39.9 (SD 3.8) mmol/mol,
      fasting serum insulin 28.3 (SD 27.8) MUU/mL. At follow-up, improvements had
      occurred in VO2max (3.2 mL/kg/min; p=0.02), systolic blood pressure (-10.6 mm Hg;
      p=0.003), HbA1c (-1.1 mmol/mol; p=0.03) and weekly vigorous (4 hours, p=0.002)
      and moderate (2 hours, p=0.006) physical activity, although waist circumference
      increased (p=0.005). Programme attendance was over 50%. Comments were mostly
      positive. DISCUSSION: The after-school exercise and lifestyle programme and study
      methods were feasible. Such programmes have the potential to improve health
      outcomes for Pacific and Maori adolescents.

PMID- 25770718
TI  - Chlamydia trachomatis screening in pregnancy in New Zealand: translation of
      national guidelines into practice.
AB  - INTRODUCTION: Chlamydia trachomatis (C. trachomatis) is a common sexually
      transmitted infection (STI), and routine antenatal screening to reduce the risk
      of vertical transmission is recommended in New Zealand (NZ). AIM: To determine
      the proportion of pregnant women who have been screened for C. trachomatis in
      selected hospitals since the 2008 NZ Ministry of Health Chlamydia Management
      Guidelines were published, and to examine variation by age and ethnicity.
      METHODS: Clinical audits were undertaken at four NZ hospitals, using electronic
      databases to determine if C. trachomatis screening had occurred. RESULTS: Only
      24%, 31%, 35% and 61% of pregnant women were screened in Tauranga (2010),
      Auckland (2013), Waikato (2013) and Middlemore (2011) hospitals, respectively.
      DISCUSSION: Despite increases in the proportion of pregnant women screened in
      Auckland and Middlemore compared to pre-2008, and higher proportions of young
      women and Maori women screened, overall antenatal screening for C. trachomatis
      remains suboptimal. Several strategies are presented to support universal
      screening in pregnancy, as recommended by the NZ Ministry of Health.

PMID- 25770719
TI  - Lead maternity care needs to be embedded in general practice: Yes.

PMID- 25770720
TI  - Lead maternity care needs to be embedded in general practice: No.

PMID- 25770721
TI  - The ethics of treating depression in pregnancy.

PMID- 25770722
TI  - Peer support workers: an untapped resource in primary mental health care.
AB  - The treatment of moderate to severe mental illness in a primary health care
      setting is an area under development and can be contentious. The capacity,
      capability, resourcing and willingness of staff and organisations all feature in
      the discussions among specialist services and primary health care providers about
      the opportunities and barriers associated with primary mental health care. This
      paper presents the peer support worker as an untapped resource that has the
      potential to support the patient, primary health care staff, and general
      practitioner in the care of people who fall outside the current understanding of
      "mild" mental health problems, but who would nonetheless benefit from receiving
      their care in a primary health care setting.

PMID- 25770723
TI  - Reply: To PMID 25770724.

PMID- 25770724
TI  - Editorial comment.

PMID- 25770725
TI  - A contemporary analysis of Fournier gangrene using the National Surgical Quality
      Improvement Program.
AB  - OBJECTIVE: To determine a nationwide contemporary description of surgical
      Fournier gangrene (FG) and necrotizing fasciitis of the genitalia (NFG) outcomes
      because historically reported mortality rates for FG and NFG are based on small
      single-institution studies from the 1980s and the 1990s. METHODS: The National
      Surgical Quality Improvement Program is a risk-adjusted surgical database used by
      nearly 400 hospitals nationwide, which tracks preoperative, intraoperative, and
      30-day postoperative clinical variables. Data are extracted from patient charts
      by an independent surgical clinical reviewer at each hospital. Using the National
      Surgical Quality Improvement Program data from 2005 to 2009, we calculated 30-day
      mortality rates and identified preoperative factors associated with increased
      mortality. RESULTS: A total of 650 patients were identified with surgery for FG
      or NFG. Fourteen patients with do not resuscitate orders placed preoperatively
      were excluded from analyses. For the remaining 636 patients, the overall 30-day
      mortality was 10.1% (64 of 636). Fifty-seven percent of patients (360 of 636)
      were men, 70% (446 of 636) were white, and 13% (81 of 636) were African American.
      Multivariate logistic regression indicated that increased age (odds ratio [OR],
      1.041; P = .004), body mass index (OR, 1.045; P <.001), and preoperative white
      blood cell count (OR, 1.061; P = .001), and decreased platelet count (OR, 0.993;
      P <.001) were all associated with increased risk of death. CONCLUSION: We
      determined a surgical mortality rate for FG-NFG of 10.1%. This rate is about half
      of historically published estimates and similar to recent studies. The lower rate
      may indicate improvements in therapy. Increased age, body mass index, and white
      blood cell count, and decreased platelet count were all associated with an
      increased risk of 30-day mortality.

PMID- 25770726
TI  - Multidisciplinary management of complex vascular malformation invading bladder
      wall.
AB  - A 5-year-old African American male patient, with a history of complex vascular
      anomalies, underwent treatment for an infiltrating urinary bladder malformation
      initially misdiagnosed as a rhabdomyosarcoma. Neodymium:yttrium-aluminum-garnet
      laser was used to treat the bladder wall before surgical resection. Vascular
      malformations of the bladder are rare. This report demonstrates a multimodal
      technique for management of large infiltrating bladder venous and lymphatic
      malformation. At the 3-month follow-up, his symptoms have resolved and his
      cystoscopy demonstrated no evidence of residual disease. 

PMID- 25770727
TI  - Editorial comment.

PMID- 25770728
TI  - Solifenacin or mirabegron could improve persistent overactive bladder symptoms
      after dutasteride treatment in patients with benign prostatic hyperplasia.
AB  - OBJECTIVE: To evaluate the clinical response and adverse events (AEs) of
      solifenacin (SOL) or mirabegron (MIR) in benign prostatic hyperplasia patients
      with persistent overactive bladder (OAB) symptoms after dutasteride (DUT)
      treatment. METHODS: Fifty cases with residual OAB symptom score (OABSS) >= 5 and
      OABSS Q3 >= 2 after at least 6 months treatment of DUT were included in this
      study. Patients were administered 5 mg/d of SOL (N = 25) or 50 mg/d of MIR (N =
      25), and International Prostate Symptom Score (IPSS) and OABSS were prospectively
      collected at 4 and 12 weeks. The safety was evaluated by changes in postvoided
      residual urine volume and the incidence of AEs. RESULTS: After DUT
      administration, the mean prostate volume, IPSS, and OABSS were 39.0 mL, 17.6, and
      8.1, respectively. SOL 5 mg significantly reduced the IPSS, OABSS, and OABSS Q3
      at 4 and at 12 weeks (-3.1, -2.7, -1.3; P <.05); however, 4 patients could not
      continue the SOL treatment owing to AEs. All patients could continue the 12 weeks
      of MIR treatment, and MIR 50 mg reduced IPSS and OABSS at 4 weeks and reduced
      IPSS, OABSS, and the OABSS Q3 (-3.0, -2.5, -0.9; P <.05) at 12 weeks. Postvoided
      residual urine volume increased by >= 100 mL after treatment in 2 cases in the
      SOL group but not in any patient in the MIR group. CONCLUSION: Additional SOL or
      MIR might result in amelioration of the persistent OAB symptom after DUT
      treatment in patients with an enlarged prostate.

PMID- 25770729
TI  - Pharmacologic and Molecular Characterization of Underactive Bladder Induced by
      Lumbar Canal Stenosis.
AB  - OBJECTIVE: To investigate the voiding function in a rat model of lumbar canal
      stenosis (LCS) using pharmacologic and molecular approaches. METHODS: Sixty-one
      female Sprague-Dawley rats were broadly split into a sham and an LCS group. A
      hole was surgically drilled in the L5-L6 epidural space and filled with a
      rectangular piece of silicone rubber. Metabolic cage study at week 2 and
      continuous cystometry (CMG) under urethane anesthesia at weeks 2 and 4 were
      performed. During CMG, prostaglandin E2 or sulprostone, an prostaglandin E
      receptor 1 and prostaglandin E receptor 3 agonist was administered locally and
      intravenously, respectively, and the bladder was then harvested for histology and
      Western blot. RESULTS: Compared with sham, the LCS group showed dribbling
      urination and progressive increase in bladder size. CMG under urethane anesthesia
      in the LCS group was marked by overflow incontinence and acontractile bladder.
      Administration of intravesical prostaglandin E2 (200 MUM) or intravenous
      sulprostone (0.1 mg/kg) in the sham group induced bladder overactivity, but
      decreased the compliance and failed to restore the bladder emptying function in
      the LCS group. The LCS group showed edematous changes and muscle thinning at week
      2, which were partially restored by week 4. Histologic changes were accompanied
      by downregulation of agrin protein (64.0%) at week 2 and upregulation of M2
      receptor (65.4%) at week 4. Expression of M3, protein gene product 9.5, and nerve
      growth factor did not differ between groups. CONCLUSION: LCS-induced underactive
      bladder is associated with altered expression of agrin and M2 receptor. The
      underactive bladder model is clinically relevant, and the findings indicate
      potential molecular targets for new therapies.

PMID- 25770730
TI  - Paraplegia-quadriplegia Independently Increases All Percutaneous Nephrolithotomy
      Complications: A Comparative Study Using the Modified Clavien System.
AB  - OBJECTIVE: To investigate the perioperative complication rates for paraplegic
      quadriplegic patients (PQPs) undergoing percutaneous nephrolithotomy (PCNL) as
      compared with non-PQPs using a standardized method of complication reporting via
      the Clavien system. METHODS: Two hundred thirteen consecutive PCNLs performed by
      a single surgeon were analyzed. There were 31 and 115 patients separated into PQP
      and non-PQP groups, respectively. Data collection included demographic and
      clinical factors, as well as perioperative and delayed complications.
      Complications were organized by the Clavien grade. All- and initial-procedure
      complications were analyzed. The rate of adverse events for each Clavien grade
      was calculated, and statistical comparisons were made. The relationship between
      PQP and complication severity was investigated using univariate and multivariate
      analyses. RESULTS: There were 38 and 43 initial-procedure complications in the
      PQP and non-PQP groups, respectively. The rate of adverse events was higher
      across the spectrum of Clavien grades for the PQP group, specifically grade 1
      (48.4% vs 20.2%; P = .002), grade 2 (22.6% vs 5.3%; P = .004), grade 3b (12.9% vs
      2.6%; P = .038), grade 4a (6.5% vs 0%), and grade 4b (9.7% vs 1.8%; P = .066).
      Approximately 51.6% and 31.5% of PQPs and non-PQPs experienced >= 1
      complications, respectively (odds ratio = 2.34; P = .05). Multivariate analysis
      demonstrated paraplegia or quadriplegia status to be an independent risk factor
      for the development of perioperative complications after adjusting for
      confounding factors (odds ratio = 2.91; P = .040). CONCLUSION: PCNL complication
      rates are higher in PQPs compared with non-PQPs. This study is one of the first
      in PCNL to use a standardized reporting system to highlight high-risk individuals
      within the stone population.

PMID- 25770731
TI  - [A new form of hypophisitis following ipilimumab therapy].

PMID- 25770732
TI  - Predictive markers in breast cancer: An update on ER and HER2 testing and
      reporting.
AB  - Gene expression profiling of human tumors has provided a new paradigm for
      classifying breast carcinomas, predicting response to treatment, and risk of
      recurrence. Estrogen receptor (ER), human epidermal growth factor 2 (HER2)
      receptor, and proliferation-related genes are the main drivers of classification
      in many of the gene expression profiling tests for breast cancer. However, ER,
      progesterone receptor (PR), and HER2 receptor status remain essential in
      determining the need and type of adjuvant therapy. These biomarkers are routinely
      tested for in all invasive breast carcinomas; ER testing is also performed on
      cases of ductal carcinoma in situ (DCIS). This article will provide an update on
      current guidelines from the American Society of Clinical Oncologists (ASCO) and
      the College of American Pathologists (CAP) for ER and HER2 testing by
      immunohistochemistry (IHC) and in situ hybridization (ISH). The populations to be
      tested, antibody selection, criteria for interpretation, and reporting are
      discussed. The molecular alterations that correlate with IHC results, alternative
      methods of testing, and the current approach to complex aspects of HER2 testing,
      including heterogeneity and polysomy, also are summarized. 

PMID- 25770733
TI  - Electron cryotomography of vitrified cells with a Volta phase plate.
AB  - Electron cryotomography provides a means of studying the three dimensional
      structure of pleomorphic objects, such as organelles or cells, with a resolution
      of 1-3nm. A limitation in the study of radiation sensitive biological samples is
      the low signal-to-noise ratio of the tomograms which may obscure fine details. To
      overcome this limitation, the recently developed Volta phase plate (VPP) was
      applied in electron cryotomographic studies of a wide range of cellular
      structures, from magnetotactic bacteria to primary cultured neurons. The results
      show that the VPP improves contrast significantly and consequently the signal-to
      noise ratio of the tomograms, moreover it avoids disturbing fringing artifacts
      typical for Zernike phase plates. The contrast improvement provided by the VPP
      was also confirmed in projection images of relatively thick (~400nm) samples. In
      order to investigate the respective contributions of the VPP and the energy
      filter, images acquired with different combinations of the two were compared.
      Zero-loss energy filtering reduced the background noise in thicker areas of the
      sample and improved the contrast of features such as poly-beta-hydroxybutyrate
      granules in magnetotactic bacteria, whereas the VPP provided an overall contrast
      improvement for all sample areas. After 3D reconstruction, tomograms acquired
      with the combination of a VPP and an energy filter showed structural features in
      neuronal processes with outstanding clarity. We also show that the VPP can be
      combined with focused ion beam milling to examine structures embedded deeply
      inside cells. Thus, we expect that VPP will become a standard element of the
      electron cryotomography workflow. 

PMID- 25770734
TI  - Nuisances and welfare of free-roaming cats in urban settings and their
      association with cat reproduction.
AB  - Free roaming cats (FRC) are highly abundant in cities around the world.
      Increasing populations of these cats might result in impairment of cat welfare
      and cause nuisances and public health risks. In order to study the seasonal
      dynamics of FRC populations and its association with events of cat welfare
      impairment and nuisances, we analyzed a database of FRC-associated citizens'
      telephone complaint events, which were registered in five cities in Israel (total
      human population of 1.42 million residents) during the years 2007-2011. These
      complaint events were classified to the following six categories: cat's
      carcasses, kittens, parturition, aggressive behavior toward people, invasion to
      human facilities, and cat injuries and distress. Overall, 87,764 complaint events
      associated with these categories were registered in the five cities during the
      study period (123.2 complaint events per 10,000 citizens per year). Length of
      daylight was moderately correlated with the rate of complaints on kittens in the
      same month (r=0.64) and parturition in the previous month (r=0.54) (P<0.001).
      Both kitten and parturition-related complaints showed a prominent seasonal
      pattern, peaking in April and May, respectively, and declining gradually until
      November. 'Kittens' or 'parturition' were explicitly mentioned in 38%, 39% and
      19%, respectively, of the complaints regarding cat aggressiveness toward people,
      cat invasion to human facilities and cat injuries and distress. In most of the
      cities the rate of citizen complaints regarding carcasses, aggression, invasion
      and injuries were still significantly correlated with rate of complaints
      regarding kittens after omission of these joint complaints and remained
      significant after controlling for seasonality. These findings imply an
      association of cat welfare impairment and nuisances with FRC reproduction
      intensity. The current study revealed the high rate of nuisances and potential
      public health hazards related to FRC, as well as the impairment of cat welfare,
      which might be merely 'the tip of the iceberg' of the real welfare situation of
      these cats. Further studies should examine the effectiveness of FRC population
      control strategies for the reduction of the rate of nuisances and public health
      risks related to FRC, as well as for improving their welfare. 

PMID- 25770736
TI  - Patient preferences in access to breast reconstruction.
AB  - BACKGROUND: Patient access to breast reconstruction is an important component of
      comprehensive breast cancer care. There is currently considerable variability in
      the timing of consultation with a plastic and reconstructive surgeon after the
      initial diagnosis of breast cancer. This study aims to elucidate patients'
      preferences for the timing of plastic surgery consultation as part of the
      preoperative evaluation and planning process. METHODS: A 16-question electronic
      survey instrument was developed based on formative patient comments and
      discussion between the breast oncology and plastic surgery teams. The survey was
      administered to all patients referred to the plastic and reconstructive surgery
      clinic for initial reconstructive consultation during the study period. RESULTS:
      A total of 31 responses were collected. The largest number of patients (48%)
      indicated they would prefer to see a plastic surgeon 1 wk after their first
      consultation with a breast surgeon. Only one patient reported a desire to see
      both surgeons on the same day. Most patients indicated that having a family
      member or friend accompany them to the appointment (45%) and having time to
      process their cancer diagnosis before seeing the plastic surgeon (32%) were key
      factors in deciding when they would like to discuss reconstruction. CONCLUSIONS:
      Most patients in our study indicated a preference for delay between initial
      consultation with a breast surgeon and initial consultation with a plastic
      surgeon. Incorporating patient preferences into the preoperative evaluation and
      planning process allows patients to optimize available support from loved ones
      and to begin coping with their diagnosis.

PMID- 25770735
TI  - Radioguided parathyroidectomy for tertiary hyperparathyroidism.
AB  - BACKGROUND: Tertiary hyperparathyroidism (3HPT) is defined as the persistent
      hyperproduction of parathyroid hormone and resulting hypercalcemia after renal
      transplantation. Here, we examine the utility of radioguided parathyroidectomy
      (RGP) in patients with 3HPT. MATERIALS AND METHODS: We reviewed a prospective
      surgery database containing 80 3HPT patients who underwent RGP from January 2001
      July 2014 at our institution. We evaluated patient demographics, operative
      management, radioguided neoprobe utilization, and operative outcomes. Data are
      reported as mean +/- standard error of the mean. RESULTS: The mean age of the
      patients was 52 +/- 1 y, and 46% were male. A total of 69 patients had
      hyperplasia and received subtotal parathyroidectomy, whereas 5 patients had
      double adenomas and 6 patients had single adenomas. The average calcium level
      among 3HPT patients was 10.8 +/- 0.1 mg/dL preoperatively and 8.7 +/- 0.1 mg/dL
      postoperatively. In vivo radioguided counts normalized to background counts
      averaged 145 +/- 4%, whereas ex vivo counts normalized to background counts
      averaged 69 +/- 5%. All but one ex vivo count was >20%. Ectopically located
      glands were successfully localized in 38 patients using the gamma probe. Ex vivo
      percentage did not correlate with parathyroid gland weight, preoperative
      parathyroid hormone, or preoperative calcium. Our radioguided approach achieved
      normocalcemia in 96% of 3HPT patients undergoing RGP; two patients developed
      recurrent disease. CONCLUSIONS: In this series, all enlarged parathyroid glands
      were localized and resected using the gamma probe. Thus, RGP reliably localizes
      adenomatous, hyperplastic, and ectopically located glands in patients with 3HPT,
      resulting in high cure rate after resection.

PMID- 25770737
TI  - Same day discharge after laparoscopic cholecystectomy in children.
AB  - BACKGROUND: Although the safety of same day discharge (SDD) after laparoscopic
      cholecystectomy (LC) for symptomatic cholelithiasis (SC) and biliary dyskinesia
      (BD) in adults has been well documented in the literature, the same data in the
      pediatric population are lacking. We have recently instituted a protocol for SDD
      after LC for SC and BD, and this study is an analysis of our initial experience.
      METHODS: A retrospective chart review of all patients who underwent LC for BD and
      SC in our institution from January 2011-July 2014 was performed. RESULTS: A total
      of 227 LC were performed for SC and BD during the study period. Approximately 25%
      (n = 57) of patients were in the SDD group. The remaining 75% (n = 170) of
      patients were admitted at least overnight stay (ONS) for the following reasons:
      medical 16.5% (n = 28), surgery ending too late 4.1% (n = 7), or clinical care
      habits 79.4% (n = 135). Comparing the SDD group with ONS group, no differences
      were found in the complication rate, readmissions, or follow up before scheduled
      appointment. Length of stay was significantly less for the SDD group than for the
      ONS. A trend for more SDDs was observed as time elapsed from initiation of the
      protocol. Also, earlier completion of surgery trended toward SDD. CONCLUSIONS:
      SDD appears safe for pediatric patients undergoing LC for BD or SC. The main
      obstacles to discharge were time of surgery completion and clinical care habits,
      both of which improved as comfort level with SDD grew among the staff.

PMID- 25770738
TI  - Selective bowel decontamination improves the survival of 90% hepatectomy in rats.
AB  - BACKGROUND: Clinically, hepatectomy is a clean procedure performed without
      routine antimicrobial prophylaxis, regardless of the extent of liver loss.
      Translocation of endotoxin has been recognized as a fatal complication leading to
      liver failure. After extended hepatectomy, the portal hypertension, mucosal
      damage, intrahepatic bile acid retention, inhibited enterokinesia, and so forth
      are likely to contribute to enhanced endotoxin absorption. The effect of
      selective bowel decontamination (SBD) on the prognosis of hepatectomy were
      investigated. METHODS: We adopted rat models of partial hepatectomy (70%, PHx)
      and subtotal hepatectomy (90%, SHx), gentamicin or saline of the same amount was
      administrated preoperatively. Liver damage makers, portal and systemic
      lipopolysaccharide, mucosal damage, signaling pathways, liver regeneration, and
      bile canalicular networks reconstruction were investigated. RESULTS: We found
      that SHx but not PHx resulted in significantly enhanced portal and systemic
      endotoxin. Inhibition of gastrointestinal gram-negative bacteria by gentamicin
      significantly reduced lipopolysaccharide levels and improved survival after SHx
      (56% with gentamicin, 24% with saline, P < 0.05). We also found SBD with
      gentamicin protected intestinal mucosa barrier, alleviated liver parenchymal
      damage, and promoted liver regeneration and bile canalicular networks
      reconstruction after extended liver resection. CONCLUSIONS: We conclude that SBD
      is beneficial and necessary for extended hepatectomy.

PMID- 25770739
TI  - Effect of adenosine triphosphate-sensitive potassium activation on peripheral and
      central pain sensitization.
AB  - BACKGROUND: Alterations in adenosine triphosphate-sensitive potassium (KATP)
      activity and expression under changing physiological conditions are important
      adaptive and protective mechanisms. KATP subunit expression is also altered in
      neuropathic pain; whether these changes are adaptive or deleterious is unclear.
      We therefore established a skin/muscle incision and retraction (SMIR) rat model
      of postoperative pain and examined the relationship between pain sensitization
      and changes in KATP subunit expression. METHODS: Rats were randomly divided into
      untreated, sham-operation, SMIR, and SMIR + Pinacidil (sulfonylurea receptor
      [SUR]2-activator) groups. In the SMIR group, skin and muscle were retracted for 1
      h after incision. In the SMIR + Pinacidil group, Pinacidil was injected
      intraperitoneally 0.5 h before SMIR or into the spinal myelin sheath 7 d after
      SMIR. Mechanical withdrawal threshold was used as an index of pain sensitivity.
      Expression levels and localization of the KATP subunits Kir6.2, Kir6.1, SUR1, and
      SUR2 were measured by Western blotting and immunofluorescence. RESULTS: A rat
      postoperative pain model was successfully established, in which SMIR induced
      mechanical hypersensitivity (allodynia). Notably, significantly increased Kir6.1,
      Kir6.2, SUR1, and SUR2 protein expression levels were observed in tissues around
      the incision (P < 0.05). In addition, significantly decreased Kir6.1, SUR2, and
      SUR1 protein levels were obtained in spinal cord L3-L5. SMIR also starkly
      increased nerve growth factor expression in the muscle around the incision.
      Importantly, intrathecal Pinacidil injection inhibited the overexpression of
      allodynia markers and nerve growth factor. CONCLUSIONS: Hyperexcitability due to
      spinal Kir6.1 and SUR2 downregulation may be responsible for postoperative pain.
      SUR2 activation is a potential strategy to inhibit postoperative allodynia.

PMID- 25770740
TI  - Protective effect of astaxanthin against multiple organ injury in a rat model of
      sepsis.
AB  - BACKGROUND: Astaxanthin, a xanthophyll carotenoid, holds exceptional promise as
      an antioxidant, anti-inflammatory, and anticancer agent. No evidence has been
      published whether it has protective effects on sepsis. The study aimed to
      investigate the potential effects of astaxanthin on sepsis and multiple organ
      dysfunctions. MATERIALS AND METHODS: Sepsis was induced by cecal ligation and
      puncture (CLP) in Sprague-Dawley rats. Animals subjected to CLP and sham-operated
      control rats were given vehicle or astaxanthin 100 mg/kg/d by oral gavage for 7 d
      before the operation. The rats were killed at the indicated time points, and the
      specimen was collected. Cytokines and multiorgan injury-associated enzymatic and
      oxidative stress indicators were investigated. Multiorgan tissues were assessed
      histologically, the peritoneal bacterial load and the 72-h survival was observed
      too. RESULTS: Sepsis resulted in a significant increase in serum tumor necrosis
      factor-alpha, interleukin-1beta, and interleukin-6 levels showing systemic
      inflammatory response; it also caused a remarkable decrease in the superoxide
      dismutase activity and a significant increase in the malondialdehyde content
      showing oxidative damage; sepsis caused a great increase in organ injury
      associated indicators, including blood urea nitrogen, creatinine, lactate
      dehydrogenase, creatine kinase isoenzyme-MB isotype, alanine aminotransferase,
      and aspartate aminotransferase, which was confirmed by histologic examination.
      And there was a dramatical increase of colony-forming units in the peritoneal
      cavity in septic rats. Astaxanthin reversed these inflammatory and oxidant
      response, alleviated the organ injury, reduced the peritoneal bacterial load, and
      improved the survival of septic rats induced by CLP. CONCLUSIONS: Astaxanthin
      exerts impressively protective effects on CLP-induced multiple organ injury. It
      might be used as a potential treatment for clinical sepsis.

PMID- 25770741
TI  - Ozone preconditioning attenuates contrast-induced nephropathy in rats.
AB  - BACKGROUND: Contrast-induced nephropathy (CIN) is an important complication of
      vascular interventions. Ozone therapy can induce tolerance to ischemic insults, a
      phenomenon known as ozone oxidative preconditioning (OOP). The aim of this study
      was to investigate the effects of OOP on CIN. MATERIALS AND METHODS: Thirty-two
      Wistar rats were randomized into four groups (n = 8). The control group had
      intravenous saline injection. The contrast media (CM) group had intravenous
      meglumine/sodium diatrizoate injection to form CIN. The ozone (O3) group received
      intraperitoneal ozone for 5 d before the induction of CIN. The oxygen (O2) group
      was given an equal amount of oxygen for 5 d before the induction of CIN. The
      animals were sacrificed 48 h after the administration of contrast agent or
      saline. Kidneys were harvested, and blood samples were obtained. Renal function
      tests, serum and renal tissue malondialdehyde (MDA), and nitric oxide (NO) levels
      and renal oxidant system parameters were determined. Histologic examination was
      performed for renal injury. RESULTS: Serum blood urea nitrogen (BUN), creatinine,
      and serum and renal MDA were increased after contrast exposure. Renal NO was
      decreased, and there was prominent tubular necrosis in the CM group. Serum BUN,
      creatinine, serum and renal MDA, and grade of tubular necrosis were decreased in
      the O3 group as compared with those in the CM group. The levels of serum and
      renal NO and renal total antioxidant system in O3 group were higher than the
      levels in the CM group. CONCLUSIONS: OOP attenuates experimental CIN. This effect
      is suggested to be mediated by reinforcement of renal antioxidant defenses and
      maintenance of renal NO levels.

PMID- 25770742
TI  - A meta-analysis of robotic versus laparoscopic colectomy.
AB  - BACKGROUND: Robotics, as an innovation of minimally invasive surgical methods, is
      developing rapidly for colectomy. But there is still no consensus on its
      comparative merit compared with laparoscopic resections. We conducted this meta
      analysis that included randomized controlled trials and nonrandomized controlled
      trials of robotic colectomy (RC) versus laparoscopic colectomy (LC) to evaluate
      whether the safety and efficacy of RC are equivalent to those of LC. METHODS: A
      search of five databases (PubMed, Embase, Cochrane Library, Ovid, and Web of
      Science), gray literature, hand searches, reference, and forward citation were
      performed for studies that compared clinical or oncologic outcomes of LC with RC.
      Clinical outcomes evaluated were conversion rates, operation times, estimated
      blood loss, length of hospital stay, and complications. Oncologic outcome
      evaluated was the number of lymph nodes collected. RESULTS: A total of 14 studies
      were identified that included 125,989 patients in total, 4934 in the robotic
      cohort and 121,055 in the laparoscopic cohort. Meta-analysis suggested that there
      was a significantly longer hospital stay in the laparoscopic group (mean
      difference [MD] -0.65; 95% confidence interval [CI] -1.02 to -0.27; P = 0.0008).
      Robotic surgery was associated with a significantly lower complication rate (odds
      ratio 0.78; 95% CI 0.72-0.85; P < 0.00001) and a significantly shorter time to
      recovery of bowel function (MD -0.58; 95% CI -0.96 to -0.20; P = 0.003). There
      were statistically significant differences in estimated blood loss (MD -19.24;
      95% CI -29.38 to -9.09; P = 0.0002) and intraoperative conversion to open (odds
      ratio 0.56; 95% CI 0.44-0.72; P < 0.00001), but not clinical relevant. There were
      no significant differences in the number of lymph nodes extracted between the two
      groups. However, operating time (MD 49.25; 95% CI 36.78-61.72; P < 0.00001) was
      longer for RC than for LC. CONCLUSIONS: RC can be performed safely and
      effectively with the number of lymph nodes extracted similar to LC. In addition,
      it can provide potential advantages of a shorter hospital stay, a shorter time to
      recovery of bowel function, and lower occurrence of postoperative complications.
      These findings seem to support the use of robotics for the minimally invasive
      surgical management of colectomy. However, RC had longer operating time. Future
      studies involving RC should focus on minimizing duration of operation.

PMID- 25770743
TI  - Prognostic factors in solitary fibrous tumors of the pleura.
AB  - BACKGROUND: Solitary fibrous tumors of the pleura (SFTP) are rare neoplasms
      originating from submesothelial mesenchymal cells with fibroblastic
      differentiation. The clinical behavior of SFTPs is mostly benign; however, up to
      20% of patients develop local recurrence and/or distant metastasis. Although
      different risk-stratification models have been described, definitive criteria to
      predict a malignant clinical course of SFTP are still lacking. METHODS: In a
      retrospective analysis at a single-institution, 25 patients with histologically
      proven SFTP were identified. Clinicopathologic and survival data were collected
      and pathologic sections reviewed. Different markers and risk-stratification
      models were correlated with disease- and overall-free survival by Kaplan-Meier
      analysis. RESULTS: Of 25 SFTP, 8 tumors (32%) were classified as malignant
      according to the World Health Organization criteria. Three patients (12%)
      developed recurrence. Cohort median follow-up was 28 mo, and median overall
      survival was 160 mo. Comparison of proliferation markers showed higher mitosis
      count per high-power field and MIB-1 labeling index (MIB) in malignant compared
      with nonmalignant SFTP. MIB was identified as a predictor for disease-free
      survival. Applying the previously reported classifications to categorize SFTP
      according to the probability to show malignant behavior, significant differences
      in disease-free survival were also present in our cohort. CONCLUSIONS: In the
      present analysis of rare SFTP, previously proposed staging systems were
      applicable for prediction of disease-free survival. Independently of treatment,
      MIB was the only sole predictive marker. A prospective multi-institutional
      database could be helpful in establishing detailed predictive criteria in
      patients diagnosed with SFTP.

PMID- 25770744
TI  - Evolution of the indoor biome.
AB  - Few biologists have studied the evolutionary processes at work in indoor
      environments. Yet indoor environments comprise approximately 0.5% of ice-free
      land area--an area as large as the subtropical coniferous forest biome. Here we
      review the emerging subfield of 'indoor biome' studies. After defining the indoor
      biome and tracing its deep history, we discuss some of its evolutionary
      dimensions. We restrict our examples to the species found in human houses--a
      subset of the environments constituting the indoor biome--and offer preliminary
      hypotheses to advance the study of indoor evolution. Studies of the indoor biome
      are situated at the intersection of evolutionary ecology, anthropology,
      architecture, and human ecology and are well suited for citizen science projects,
      public outreach, and large-scale international collaborations.

PMID- 25770745
TI  - Hepatic abscess: Diagnosis and management.
AB  - Microbial contamination of the liver parenchyma leading to hepatic abscess (HA)
      can occur via the bile ducts or vessels (arterial or portal) or directly, by
      contiguity. Infection is usually bacterial, sometimes parasitic, or very rarely
      fungal. In the Western world, bacterial (pyogenic) HA is most prevalent; the
      mortality is high approaching 15%, due mostly to patient debilitation and
      persistence of the underlying cause. In South-East Asia and Africa, amebic
      infection is the most frequent cause. The etiologies of HA are multiple including
      lithiasic biliary disease (cholecystitis, cholangitis), intra-abdominal
      collections (appendicitis, sigmoid diverticulitis, Crohn's disease), and bile
      duct ischemia secondary to pancreatoduodenectomy, liver transplantation,
      interventional techniques (radio-frequency ablation, intra-arterial chemo
      embolization), and/or liver trauma. More rarely, HA occurs in the wake of
      septicemia either on healthy or preexisting liver diseases (biliary cysts,
      hydatid cyst, cystic or necrotic metastases). The incidence of HA secondary to
      Klebsiella pneumoniae is increasing and can give rise to other distant septic
      metastases. The diagnosis of HA depends mainly on imaging (sonography and/or CT
      scan), with confirmation by needle aspiration for bacteriology studies. The
      therapeutic strategy consists of bactericidal antibiotics, adapted to the germs,
      sometimes in combination with percutaneous or surgical drainage, and control of
      the primary source. The presence of bile in the aspirate or drainage fluid
      attests to communication with the biliary tree and calls for biliary MRI looking
      for obstruction. When faced with HA, the attending physician should seek advice
      from a multi-specialty team including an interventional radiologist, a
      hepatobiliary surgeon and an infectious disease specialist. This should help to
      determine the origin and mechanisms responsible for the abscess, and to then
      propose the best appropriate treatment. The presence of chronic enteric biliary
      contamination (i.e., sphincterotomy, bilio-enterostomy) should be determined
      before performing radio-frequency ablation and/or chemo-embolization; substantial
      stenosis of the celiac trunk should be detected before performing
      pancreatoduodenectomy to help avoid iatrogenic HA. 

PMID- 25770746
TI  - Ogilvie's syndrome-acute colonic pseudo-obstruction.
AB  - Ogilvie's syndrome describes an acute colonic pseudo-obstruction (ACPO)
      consisting of dilatation of part or all of the colon and rectum without intrinsic
      or extrinsic mechanical obstruction. It often occurs in debilitated patients. Its
      pathophysiology is still poorly understood. Since computed tomography (CT) often
      reveals a sharp transition or "cut-off" between dilated and non-dilated bowel,
      the possibility of organic colonic obstruction must be excluded. If there are no
      criteria of gravity, initial treatment should be conservative or pharmacologic
      using neostigmine; decompression of colonic gas is also a favored treatment in
      the decision tree, especially when cecal dilatation reaches dimensions that are
      considered at high risk for perforation. Recurrence is prevented by the use of a
      multiperforated Faucher rectal tube and oral or colonic administration of
      polyethylene glycol (PEG) laxative. Alternative therapeutic methods include:
      epidural anesthesia, needle decompression guided either radiologically or
      colonoscopically, or percutaneous cecostomy. Surgery should be considered only as
      a final option if medical treatments fail or if colonic perforation is suspected;
      surgery may consist of cecostomy or manually-guided transanal pan-colorectal tube
      decompression at open laparotomy. Surgery is associated with high rates of
      morbidity and mortality. 

PMID- 25770747
TI  - Familial Q fever clustering with variable manifestations imitating infectious and
      autoimmune disease.
AB  - Q fever, caused by Coxiella burnetii, can present as an outbreak of acute disease
      ranging from asymptomatic disease, pneumonia, hepatitis or fever of unknown
      origin, which can progress to a chronic disease, most frequently endocarditis.
      The occurrence of Q fever within families is rarely described, and in most cases
      presents with uniform acute disease manifestations. Here we present a familial
      cluster of Q fever presenting as highly variable synchronous manifestations in
      four of five family members, including prolonged fever of unknown origin,
      asymptomatic carrier state, hepatitis, and chronic endocarditis developing in the
      absence of previous symptoms. This case series highlights the possibility of Q
      fever developing in cohabitated individuals with highly variable symptoms masking
      the common disease etiology. Screening of all exposed individuals, even those not
      clinically suspected to be infected, may enable to better identify, treat and
      prevent progression to chronic disease. 

PMID- 25770748
TI  - National estimated costs of never events following radical prostatectomy.
AB  - OBJECTIVE: To examine the Centers for Medicare and Medicaid Services, which since
      2008 has identified and not reimbursed 10 common postoperative complications
      deemed "never events" or hospital-acquired conditions (HACs). Prostate cancer,
      the most frequent cancer among U.S. men, is most often treated with radical
      prostatectomy (RP). Therefore, its complications in total may represent
      significant costs to hospitals and providers if not reimbursed. We evaluated the
      potential effect of these unreimbursed HACs following RP on clinical outcomes and
      costs. METHODS AND MATERIALS: Using the Nationwide Inpatient Sample, we selected
      a weighed, national, estimated sample of 451,707 men with prostate cancer who
      underwent RP between 2002 and 2009. Baseline sociodemographic and hospital
      characteristics are described. We calculated estimated frequencies and costs of
      HACs and the predictors of in-hospital mortality, prolonged length of stay, and
      increased total hospital costs. RESULTS: Overall, HACs were infrequent at 0.08%,
      with pressure ulcer development (0.02%) and foreign object retained at surgery
      (0.02%) being the most common. HAC occurrence was not affected by hospital
      teaching status or surgical volume, but larger hospital size was related to more
      HACs. Those experiencing an HAC were much more likely to have a prolonged length
      of stay (odds ratio = 6.68, 95% CI: 5.34-8.36) and increased hospital costs (odds
      ratio = 5.03, 95% CI: 4.05-6.24). HACs after RP cost an estimated nearly $1
      million annually in the United States. CONCLUSION: In a robust sample of patients
      who underwent RP in the United States, HACs were very uncommon and contributed
      approximately $1 million in additional expenditures. As the U.S. government
      continues to expand quality improvement programs and develop incentives to avoid
      complications, efforts to monitor unnecessary complications should continue as
      well.

PMID- 25770749
TI  - Procainamide-induced pulmonary fibrosis after orthotopic heart transplantation: a
      case report and literature review.
AB  - A 33-year-old African-American woman was bridged to heart transplantation with a
      left ventricular assist device. She had a 14-month history of heart failure
      secondary to viral cardiomyopathy. The patient's refractory ventricular
      tachycardia was treated with intravenous procainamide owing to the patient's
      history of amiodarone-induced thyroiditis. After orthotopic cardiac transplant,
      she experienced prolonged respiratory failure. Serial computed tomography
      evaluation of the lung revealed diffuse bilateral ground-glass opacities and
      septal thickening. Bronchoscopies with tissue biopsies were performed with no
      conclusive results. Specimen samples displayed septal fibrosis with loose
      fibromyxoid tissue and some hobnail nodularities with no indication of
      granulomas, neutrophilic infiltration, malignancy, or fungal, viral, or bacterial
      growth. Histopathological evaluation of the lung wedge biopsy supported a
      diagnosis of pulmonary fibrosis and noted interstitial fibrosis with areas of
      focal alveolar hemorrhage and increased macrophage infiltration. Antinuclear body
      was found to be negative. After in-depth evaluation of the patient's medication
      history, procainamide was identified as the cause of the toxicity. As
      procainamide-induced lung fibrosis is relatively uncommon, we present this case
      to highlight procainamide's potential harm and the need for careful monitoring in
      postsurgical patients. 

PMID- 25770750
TI  - Obesity in laparoscopic surgery.
AB  - Since the 1980s, minimally invasive techniques have been applied to an increasing
      number and variety of surgical procedures with a gradual increase in the
      complexity of procedures being successfully performed laparoscopically. In the
      past, obesity was considered a contraindication to laparoscopy due to the higher
      risk of co-morbid conditions such as diabetes, hypertension, coronary artery
      disease and venous thromboembolism. Performing laparoscopic gynaecological
      procedures in morbidly obese patients is no longer a rare phenomenon; however, it
      does necessitate changes in clinical practice patterns. Understanding of the
      physiological changes induced by laparoscopy, particularly in obese patients, is
      important so that these may be counteracted and adverse outcomes avoided.
      Laparoscopy in obese patients confers certain advantages such as shorter hospital
      stay, less post-operative pain and fewer wound infections. In addition to these
      benefits, minimal-access surgery has been demonstrated as safe and effective in
      obese patients; however, specific surgical strategies and operative techniques
      may need to be adopted. 

PMID- 25770751
TI  - Effects of degeneration on the compressive and tensile properties of human
      meniscus.
AB  - Healthy menisci function within the joint to prevent the underlying articular
      cartilage from excessive loads. Understanding how mechanical properties of
      menisci change with degeneration can drive future therapeutic studies to prevent
      this degeneration. Thus, the goal of this study was to characterize both
      compressive and tensile moduli of human menisci with varying degrees of gross
      damage due to osteoarthritis (OA). Twenty four paired menisci were collected from
      total knee joint replacement patients and the menisci were graded on a scale from
      0-4 according to level of gross meniscal degeneration with 0=normal and 4=full
      tissue maceration. Each meniscus was then sectioned into anterior and posterior
      regions and subjected to indentation relaxation tests. Samples were sliced into
      1mm thick strips, made into dumbbells using a custom punch, and pulled to
      failure. Significant decreases in instantaneous compressive modulus were seen in
      the lateral posterior region between grades 0 and 1 (36% decrease) and in the
      medial anterior regions between grades 1 and 2 (67% decrease) and 1 and 3 (72%
      decrease). Changes in equilibrium modulus where seen in the lateral anterior
      region between grades 1 and 2 (35% decrease), lateral posterior region between
      grades 0-2 (41% decrease), and medial anterior regions between grades 1 and 2
      (59% decrease), 1 and 3 (67% decrease), 2 and 4 (54% decrease), and 3 and 4 (42%
      decrease). No significant changes were observed in tensile modulus across all
      regions and degenerative grades. The results of this study demonstrate the
      compressive moduli are affected even in early stages of gross degeneration, and
      continue to decrease with increased deterioration. However, osteoarthritic
      menisci retain a tensile modulus similar to that of previously reported healthy
      menisci. This study highlights progressive changes in meniscal mechanical
      compressive integrity as level of gross tissue degradation increases, and thus,
      early interventions should focus on restoring or preserving compressive
      integrity. 

PMID- 25770752
TI  - Stochastic description of the peak hip contact force during walking free and
      going upstairs.
AB  - Uncertainty quantification for the response of a patient specific femur is
      mandatory when advocating finite element (FE) models in clinical applications.
      Reliable stochastic descriptions of physiological hip contact forces are an
      essential prerequisite for such an endeavor. We therefore analyze the in-vivo
      available data of seven individuals from HIP98 and OrthoLoad with the objective
      of characterizing the variability of the peak hip contact force magnitude and two
      corresponding spatial angles (in sagittal and frontal plane) during walking free
      and going upstairs. Regression analyses with linear mixed-effects models were
      performed resulting in six normal random variables, one for each force component
      and activity. Importantly, the statistical analysis accounts for the fact that
      same individuals performed both activities. The mean of the peak force magnitude
      was found to be linearly dependent on the body weight with an additional,
      activity-specific intercept and all variances were dominated by the inter-patient
      variability. No distinct correlation was found between the two angles and the
      force magnitude. The proposed stochastic description of the peak hip contact
      force during walking free and going upstairs contributes towards future
      uncertainty quantification of patient-specific FE models. 

PMID- 25770753
TI  - Induction of fiber alignment and mechanical anisotropy in tissue engineered
      menisci with mechanical anchoring.
AB  - This study investigated the effect of mechanical anchoring on the development of
      fiber organization and anisotropy in anatomically shaped tissue engineered
      menisci. Bovine meniscal fibrochondrocytes were mixed with collagen and injected
      into molds designed to produce meniscus implants with 12 mm extensions at each
      horn. After a day of static culture, 10 and 20mg/ml collagen menisci were either
      clamped or unclamped and cultured for up to 8 weeks. Clamped menisci were
      anchored in culture trays throughout culture to mimic the native meniscus horn
      attachment sites, restrict contraction circumferentially, and encourage
      circumferential alignment. Clamped menisci retained their size and shape, and by
      8 weeks developed circumferential and radial fiber organization that resembled
      native meniscus. Clamping also increased collagen accumulation and improved
      mechanical properties compared to unclamped menisci. Enhanced organization in
      clamped menisci was further reflected in the development of anisotropic tensile
      properties, with 2-3 fold higher circumferential moduli compared to radial
      moduli, a similar ratio to native meniscus. Ten and 20mg/ml clamped menisci had
      similar levels of organization, with 20mg/ml menisci producing larger diameter
      fibers and significantly better mechanical properties. Collectively, these data
      demonstrate the benefit of using bio-inspired mechanical boundary conditions to
      drive the formation of a highly organized collagen fiber network.

PMID- 25770754
TI  - The geometric curvature of the spine of runners during maximal incremental effort
      test.
AB  - This study sought to analyse the behaviour of the average spinal posture using a
      novel investigative procedure in a maximal incremental effort test performed on a
      treadmill. Spine motion was collected via stereo-photogrammetric analysis in
      thirteen amateur athletes. At each time percentage of the gait cycle, the
      reconstructed spine points were projected onto the sagittal and frontal planes of
      the trunk. On each plane, a polynomial was fitted to the data, and the two
      dimensional geometric curvature along the longitudinal axis of the trunk was
      calculated to quantify the geometric shape of the spine. The average posture
      presented at the gait cycle defined the spine Neutral Curve. This method enabled
      the lateral deviations, lordosis, and kyphosis of the spine to be quantified
      noninvasively and in detail. The similarity between each two volunteers was a
      maximum of 19% on the sagittal plane and 13% on the frontal (p<0.01). The data
      collected in this study can be considered preliminary evidence that there are
      subject-specific characteristics in spinal curvatures during running. Changes
      induced by increases in speed were not sufficient for the Neutral Curve to lose
      its individual characteristics, instead behaving like a postural signature. The
      data showed the descriptive capability of a new method to analyse spinal postures
      during locomotion; however, additional studies, and with larger sample sizes, are
      necessary for extracting more general information from this novel methodology. 

PMID- 25770755
TI  - Design, synthesis of 6-substituted-pyrido[3,2-d]pyridazine derivatives with
      anticonvulsant activity.
AB  - Aim to find new compounds with stronger anticonvulsant activity and lower
      neurotoxicity, a novel series of 6-substituted-pyrido[3,2-d]pyridazine
      derivatives was synthesized using furo[3,4-b]pyridine-5,7-dione as the starting
      material. We evaluated their anticonvulsant activity and neurotoxicity using by
      maximal electroshock (MES) and rotarod neurotoxicity (TOX) tests. The results
      showed that N-m-chlorophenyl-[1,2,4]triazolo- [4,3-b]-pyrido[3,2- d]pyridazin-6
      amine (3) was the most potent anticonvulsant, with ED50 value of 13.6 mg/kg and
      protective index ( PI = TD50/ED50) values of 7.2 in the MES test. Compound N-m
      chlorophenyltetriazolo[5,1-b]-pyrido[3,2-d]pyridazin-6-amine (19), exhibited
      significant anticonvulsant activity in maximal electroshock test with PI value of
      13.4, which was safer than marketed drug carbamazepine. 

PMID- 25770756
TI  - Association of plasma small dense LDL cholesterol with PCSK9 levels in patients
      with angiographically proven coronary artery disease.
AB  - BACKGROUND AND AIMS: Proprotein convertase subtilisin-kexin type 9 (PCSK9) is a
      novel regulator of low-density lipoprotein (LDL) metabolism. Recently, small
      dense LDL (sdLDL) particles have been suggested to be a very atherogenic
      subspecies of LDL. To date, the association of sdLDL with PCSK9 is still unclear.
      The aim of the present study is to determine the association of sdLDL, as assayed
      by sdLDL-cholesterol (sdLDL-C), with PCSK9 in a cohort of subjects undergoing
      coronary angiography. METHODS AND RESULTS: Four hundred and ninety consecutive
      subjects were enrolled and classified into stable coronary artery disease (CAD)
      and non-CAD group. LDL separation was performed by Lipoprint System: 7 LDL
      subfractions were obtained and LDL score (% sdLDL) was calculated. The plasma
      PCSK9 levels were measured by ELISA. The data indicated that PCSK9 levels were
      significantly increased by sdLDL-C quartiles (p = 0.028). In age- and sex
      adjusted analysis plasma sdLDL-C was positively correlated with PCSK9 levels (r =
      0.157, p < 0.01). To rule out the confounding effect of dyslipidemia, we
      performed the analysis in subjects with and without dyslipidemia separately.
      Interestingly, the positive correlation of sdLDL-C with PCSK9 was only
      significant in patients with dyslipidemia and stable CAD (r = 0.177, p < 0.01).
      In a model adjusting for traditional risk factors including dyslipidemia, PCSK9
      was an independent predictor of high sdLDL-C in CAD group (OR = 12.919, 95% CI
      1.427-116.952) but not in non-CAD group. CONCLUSION: This study firstly
      demonstrated that plasma sdLDL-C was positively related to PCSK9 in patients with
      stable CAD, suggesting an interaction between sdLDL-C and PCSK9 in
      atherosclerotic coronary disease.

PMID- 25770757
TI  - Abdominal obesity is associated with arterial stiffness in middle-aged adults.
AB  - BACKGROUND AND AIMS: The relation between adiposity and arterial stiffness
      remains controversial. We determined whether abdominal and visceral adipose
      tissue may be a better predictor of arterial stiffness than general obesity in
      middle-aged adults. METHODS AND RESULTS: A total of 146 participants (76 men, 70
      women; 50 years) were studied. The automatic vascular screening device (Omron VP
      1000plus) was used to measure blood pressure simultaneously in the arms and
      ankles and to determine arterial stiffness by pulse wave velocity (PWV). Using
      multiple linear regressions, the relations between indicators of obesity and
      arterial stiffness were examined after adjustment for confounders. Both carotid
      femoral PWV and brachial-ankle PWV were significantly associated with BMI (both P
      < 0.05) but not with body fat percentage. Measures of abdominal obesity,
      including waist circumference and visceral fat mass (via DXA), were strongly
      associated with PWV and remained positively associated with arterial stiffness
      after adjustment for age and gender. Cardiovascular fitness as assessed by
      maximal oxygen consumption was related to body fat percentage but not with
      visceral fat. More favorable cardiovascular health profile was associated with
      both lower visceral fat mass and PWV (both P < 0.001). CONCLUSION: Abdominal
      obesity and visceral fat are associated with large artery stiffness. These
      findings support the importance of adiposity measures as a risk factor for
      arterial stiffening in middle-aged adults.

PMID- 25770758
TI  - Effects of non-fat dairy products added to the routine diet on vascular function:
      a randomized controlled crossover trial.
AB  - BACKGROUND AND AIMS: High consumption of low- and non-fat dairy products is
      associated with reduced risk of high blood pressure (BP) and central arterial
      stiffness. However, interventional studies to determine if the addition of non
      fat dairy products to the diet is capable of reducing central BP and improving
      vascular function are lacking. The aim of this study was to determine if the
      solitary addition of non-fat dairy products to the normal routine diet would
      reduce central BP and improve vascular function in middle-aged and older adults
      with elevated BP. METHODS AND RESULTS: Using a randomized, crossover intervention
      study design, forty-nine adults (44% men, 53 +/- 2 years, 170 +/- 2 cm, 88 +/- 3
      kg; mean +/- SEM) with elevated BP (134 +/- 1/81 +/- 1 mm Hg) underwent a High
      Dairy condition (+4 servings/day of conventional non-fat dairy products) and No
      Dairy condition (+4 servings/day fruit products) in which all dairy products were
      removed. Both dietary conditions lasted 4 weeks with a 2-week washout before
      crossing over into the alternate condition. The High Dairy condition produced
      reductions in central systolic BP (-3 +/- 1 mm Hg) and carotid-femoral pulse wave
      velocity (-0.5 +/- 0.1 m/sec), with a concomitant increase in brachial flow
      mediated dilation (+1.1 +/- 0.4%) and cardiovagal baroreflex sensitivity (+5 +/-
      1 ms/mm Hg) (P < 0.05 for all vs. baseline). In the No Dairy condition, brachial
      flow-mediated dilation was reduced (-1.0 +/- 0.1%, P < 0.05 vs. baseline).
      CONCLUSIONS: The solitary manipulation of conventional dairy products in the
      normal routine diet modulates levels of central BP and vascular function in
      middle-aged and older adults with elevated BP. CLINICAL TRIAL REGISTRATION:
      clinicaltrials.gov Identifier: NCT01577030.

PMID- 25770760
TI  - In adult patients with type 1 diabetes healthy lifestyle associates with a better
      cardiometabolic profile.
AB  - BACKGROUND/AIMS: Little is known about lifestyle habits of adults with type 1
      diabetes (T1D) and their association with cardiometabolic risk (CMR) factors. The
      aims of the present study were to determine the prevalence of adults with T1D who
      adopted a healthy lifestyle and to explore the association between a healthy
      lifestyle and the cardiometabolic profile. METHODS AND RESULTS: This is a cross
      sectional analysis of 115 adults with T1D. Participants wore a motion sensor and
      completed a 3-day food record. The following CMR factors were assessed: body mass
      index, waist circumference, body composition (iDXA), glycated hemoglobin, lipids
      and blood pressure. Insulin resistance was estimated (estimated glucose disposal
      rate). Participants were classified according to the number of healthy lifestyle
      habits adopted (ranging from 0 to 3): regular physical activity (physical
      activity level >=1.7), good diet quality (Canadian Healthy Eating Index score
      >80) and none-smoking status. The proportion of participants who adopted 3, 2, 1
      or 0 lifestyle habits were 11%, 30%, 37%, and 23%, respectively. As the number of
      healthy lifestyle habits adopted increased, participants had significantly lower
      body mass index, waist circumference, body fat, total cholesterol, non-HDL
      cholesterol, triglycerides and systolic blood pressure (p < 0.05). In addition, a
      trend for lower estimated insulin resistance was observed (p = 0.06). For each
      increase of one healthy lifestyle habit, body mass index decreased by 1.9
      kg/m(2), waist circumference by 4.0 cm for men and 4.8 cm for women and trunk fat
      by 3.6% for men and 4.1% for women. CONCLUSIONS: These results suggest the
      importance of a healthy lifestyle among adults with T1D in order to control CMR
      factors.

PMID- 25770759
TI  - Posttraumatic stress disorder, alone or additively with early life adversity, is
      associated with obesity and cardiometabolic risk.
AB  - BACKGROUND AND AIMS: There is some evidence that posttraumatic stress disorder
      (PTSD) and early life adversity may influence metabolic outcomes such as obesity,
      diabetes, and cardiovascular disease. However, whether and how these interact is
      not clear. METHODS: We analyzed data from a cross-sectional and longitudinal
      study to determine how PTSD severity influences obesity, insulin sensitivity, and
      key measures and biomarkers of cardiovascular risk. We then looked at how PTSD
      and early life adversity may interact to impact these same outcomes. RESULTS:
      PTSD severity is associated with increasing risk of obesity, diabetes, and
      cardiovascular disease, with higher symptoms correlating with higher values of
      BMI, leptin, fibrinogen, and blood pressure, and lower values of insulin
      sensitivity. PTSD and early life adversity have an additive effect on these
      metabolic outcomes. The longitudinal study confirmed findings from the cross
      sectional study and showed that fat mass, leptin, CRP, sICAM-1, and sTNFRII were
      significantly increased with higher PTSD severity during a 2.5 year follow-up
      period. CONCLUSIONS: Individuals with early life adversity and PTSD are at high
      risk and should be monitored carefully for obesity, insulin resistance, and
      cardiometabolic risk.

PMID- 25770761
TI  - Multiple symmetric lipomatosis: a rare disease and its possible links to brown
      adipose tissue.
AB  - AIM: Aim of this study is an updated review of our case series (72 patients) as
      well as available literature on the Multiple Symmetric Lipomatosis (MSL), a rare
      disease primarily involving adipose tissue, characterized by the presence of not
      encapsulated fat masses, symmetrically disposed at characteristic body sites
      (neck, trunk, proximal parts of upper and lower limbs). DATA SYNTHESIS: The
      disease is more frequent in males, associated to an elevated chronic alcohol
      consumption, mainly in form of red wine. Familiarity has been reported and MSL is
      considered an autosomic dominant inherited disease. MSL is associated to severe
      clinical complications, represented by occupation of the mediastinum by
      lipomatous tissue with a mediastinal syndrome and by the presence of a somatic
      and autonomic neuropathies. Hyper-alphalipoproteinemia with an increased adipose
      tissue lipoprotein-lipase activity, a defect of adrenergic stimulated lipolysis
      and a reduction of mitochondrial enzymes have been described. The localization of
      lipomatous masses suggests that MSL lipomas could originate from brown adipose
      tissue (BAT). Moreover, studies on cultured pre-adipocytes demonstrate that these
      cells synthetize the mitochondrial inner membrane protein UCP-1, the selective
      marker of BAT. Surgical removal of lipomatous tissue is to date the only
      validated therapeutic approach. CONCLUSIONS: MSL is supposed to be the result of
      a disorder of the proliferation and differentiation of human BAT cells.

PMID- 25770762
TI  - Bariatric surgery and prevention of cardiovascular events and mortality in morbid
      obesity: mechanisms of action and choice of surgery.
AB  - AIMS: Obesity is associated with increased cardiovascular (CV) morbidity and
      mortality. Weight loss improves several risk factors for CV diseases, but anti
      obesity medications and lifestyle interventions have failed to modify primary CV
      endpoints. This paper reviews bariatric surgery in prevention of CV diseases and
      CV mortality, and analyzes the possible mechanisms involved. DATA SYNTHESIS: In
      morbidly obese patients bariatric surgery results in stable weight loss and in
      long-term reduction in the prevalence and incidence of obesity-related
      comorbidities; controlled trials have shown superiority of bariatric surgery over
      medical therapy in inducing significant weight loss and improvement of CV risk
      factors. Bariatric surgery induces several metabolic improvements (resolution of
      type 2 diabetes mellitus, improvement of lipid metabolism and of insulin
      resistance, reduction of visceral fat, of subclinical endothelial dysfunction and
      inflammation), and functional improvements (reduction of hypertension, of
      sympathetic overactivity, of left and right ventricular hypertrophy), which can
      explain the protective effect towards CV disease. CONCLUSIONS: Reduction of CV
      diseases is mediated by the pleiotropic effects of weight loss through surgery.
      Available data do not allow conclusions on the comparative efficacy of different
      surgical techniques; the choice of the surgical technique for a single patient
      remains an open question, and it is likely that the degree of prevention of CV
      diseases depends, among other factors, on the baseline conditions of patients.
      Large prospective studies are needed to address this issue in morbidly obese
      patients.

PMID- 25770763
TI  - Factor structure and reliability of the Arabic adaptation of the Hypomania Check
      List-32, second revision (HCL-32-R2).
AB  - OBJECTIVE: To assess the psychometric properties of the Arabic adaptation of the
      Hypomania-Check-List 32-item, second revision (HCL-32-R2) for the detection of
      bipolarity in major depressive disorder (MDD) inpatients suffering a current
      major depressive episode (MDE). METHOD: The "Bipolar Disorders: Improving
      Diagnosis, Guidance, and Education" Arabic module of the HCL-32-R2 was
      administered to mother-tongue Arabic MDE inpatients between March 2013 and
      October 2014. Diagnostic and Statistical Manual Fourth edition (DSM-IV) diagnoses
      were made adopting the mini-international neuropsychiatric interview, using
      bipolar disorder (BD) patients as controls. RESULTS: In our sample (n=500, of
      whom, BD-I=329; BD-II=70; MDD=101), using a cut-off of 17 allowed the HCL-32-R2
      to discriminate DSM-IV-defined MDD patients between "true unipolar" (HCL-32-R2(
      )) and "sub-threshold bipolar depression" (HCL-32-R2(+)) with sensitivity=82% and
      specificity=77%. Area under the curve was .883; positive and negative predictive
      values were 93.44% and 73.23% respectively. Owing to clinical interpretability
      considerations and consistency with previous adaptations of the HCL-32, a two
      factor solution (F1="hyperactive/elated" vs.
      F2="irritable/distractible/impulsive") was preferred using exploratory and
      confirmatory factors analyses. Item n.33 ("I gamble more") and n.34 ("I eat
      more") introduced in the R2 version of the HCL-32 loaded onto F1, though very
      slightly. Cronbach's alphas were F1=.86 and F2=.60. LIMITATIONS: No cross
      validation with any additional validated screening tool. Inpatients only sample;
      recall bias; no systematic evaluation of eventual medical/psychiatric
      comorbidities, current/lifetime pharmacological history, or record of severity of
      current MDE. CONCLUSIONS: In our sample, the HCL-32 fairly discriminated between
      MDD and BD-I but not BD-II, therefore soliciting for replication studies for use
      in Arabic-speaking depressed inpatients.

PMID- 25770764
TI  - Epidemiology is an important contributor to clinical and public health practice
      in the Caribbean.

PMID- 25770765
TI  - Certification of Coroners cases by pathologists would improve the completeness of
      death registration in Jamaica.
AB  - OBJECTIVES: Describe the completeness and quality of Jamaica's 2008 vital
      registration mortality database. STUDY DESIGN AND SETTING: Multiple sources
      (hospitals, police, forensic pathologists, Coroners courts) were used to validate
      deaths registered as occurring in 2008. A 10% random sample was examined to
      evaluate the quality of certification and coding. Jamaica, a middle-income
      country of 2.7 million, began vital registration in 1877; however, the mortality
      database was considered of limited use, and the study was commissioned to
      understand the problem. RESULTS: Of 19,286 deaths identified, 76% were registered
      by 31.12.2009 for inclusion among 2008 demographic returns. Registration was
      highest among deaths not requiring autopsy (94%) and lowest among Coroners cases
      (22%) with only 41% of deaths among 15-44 year-olds registered. The leading
      causes of death were cerebrovascular disease, diabetes mellitus, and homicide.
      Fifteen percent were coded to ill-defined causes of death. Recoding the sample
      increased mortality from prematurity, pregnancy complications, homicide, selected
      cardiovascular disorders, and human immunodeficiency virus/AIDS. CONCLUSION:
      Delays registering Coroners cases, certification and coding errors, introduced
      biases into the disease profile limiting the data's value in informing clinical
      care. Issuance of medical certificates by pathologists who investigate Coroners
      cases and training physicians and coders would eliminate most underreporting and
      improve data quality.

PMID- 25770766
TI  - The use of functional and effective connectivity techniques to understand the
      developing brain.
AB  - Developmental neuroscience, the study of the processes that shape and reshape the
      maturing brain, is a growing field still in its nascent stages. The developmental
      application of functional and effective connectivity techniques, which are tools
      that measure the interactions between elements of the brain, has revealed insight
      to the developing brain as a complex system. However, this insight is granted in
      discrete windows of consecutive time. The current review uses dynamic systems
      theory as a conceptual framework to understand how functional and effective
      connectivity tools may be used in conjunction to capture the dynamic process of
      change that occurs with development.

PMID- 25770767
TI  - Deferred systemic therapy in patients with metastatic renal cell carcinoma.
AB  - BACKGROUND: With the advent of small-molecule "targeted" therapies, the
      prevailing treatment paradigm for metastatic renal cell carcinoma (mRCC) is that
      all patients who are able to tolerate systemic therapy should receive it.
      However, oncologists often defer the initiation of systemic therapy for patients
      with mRCC. The outcomes of and clinical reasoning behind the initial management
      of patients with mRCC without systemic therapy have not been well described.
      METHODS: We conducted a retrospective cohort study of all patients with mRCC
      treated within the Duke University Health System and diagnosed from January 1,
      2007, to January 1, 2011. We defined our cohort as patients who did not receive
      systemic therapy during the first year after mRCC diagnosis. The clinical
      rationale for the lack of immediate treatment was ascertained by manual chart
      review. RESULTS: A total of 60 of 268 patients (22%) with mRCC managed without
      initial systemic therapy were included in our study. The median age was 61.2
      years, the median duration from diagnosis of localized RCC to development of mRCC
      was 41.9 months, and 91% of patients had Eastern Cooperative Oncology Group
      functional status of <= 1. Of the patients, 60% were managed with surgical
      metastasectomy alone, 12% received multiple local treatment modalities, 13%
      received active surveillance, 7% were managed supportively, and 8% were
      categorized as "other." CONCLUSIONS: The majority of patients in our cohort had
      favorable disease characteristics and experienced favorable outcomes with surgery
      alone. Our results suggest that this population could represent 20% of patients
      with mRCC in tertiary care settings. Prospective data are needed to evaluate
      deferred systemic therapy as a management strategy.

PMID- 25770768
TI  - Long-Term Administration of Docetaxel Over 70 Cycles for Castration-Resistant
      Prostate Cancer.

PMID- 25770769
TI  - It takes two to tango: Understanding the interactions between engineered
      nanomaterials and the immune system.
AB  - The immune system represents our primary defense system against foreign
      intrusion, including pathogens as well as particles. In order to understand the
      potential toxicity of engineered nanomaterials of ever increasing sophistication,
      it is necessary to understand the sophistication of the immune system with its
      multiple, specialized cell types and soluble mediators. Moreover, it is important
      to consider not only material-intrinsic properties of the pristine nanomaterial,
      but also the acquired, context-dependent 'identity' of a nanomaterial in a living
      system resulting from the adsorption of biomolecules on its surface. The immune
      system has evolved to recognize a vast array of microbes through so-called
      pattern recognition; we discuss in the present review whether engineered
      nanomaterials with or without a corona of biomolecules could also be sensed as
      'pathogens' by immune-competent cells. 

PMID- 25770770
TI  - Undefined role of mucus as a barrier in ocular drug delivery.
AB  - Mucus layer covers the ocular surface, and soluble mucins are also present in the
      tear fluid. After topical ocular drug administration, the drugs and formulations
      may interact with mucus layer that may act as a barrier in ocular drug delivery.
      In this mini-review, we illustrate the mucin composition of the ocular surface
      and discuss the influence of mucus layer on ocular drug absorption. Based on the
      current knowledge the role of mucus barrier in drug delivery is still undefined.
      Furthermore, interactions with mucus may prolong the retention of drug
      formulations on the ocular surface. Mucus may decrease or increase ocular
      bioavailability depending on the magnitude of its role as barrier or retention
      site, respectively. Mechanistic studies are needed to clarify the role of mucin
      in ocular drug delivery. 

PMID- 25770772
TI  - Deadly infectious diseases such as Ebola: the parachute paradigm.

PMID- 25770771
TI  - Doxorubicin and curcumin co-delivery by lipid nanoparticles for enhanced
      treatment of diethylnitrosamine-induced hepatocellular carcinoma in mice.
AB  - At present, the treatment of hepatocellular carcinoma (HCC) is an international
      problem. The delivery of a chemotherapeutic agent and chemosensitizer using
      nanocarriers has been suggested as a novel and promising strategy in cancer
      treatment. However, such studies in HCC remain very limited. In this study, we
      developed doxorubicin (DOX) and curcumin (Cur) co-delivery lipid nanoparticles
      (DOX/Cur-NPs) and examined its inhibitory effect on diethylnitrosamine (DEN)
      induced HCC in mice. DOX/Cur-NPs displayed the physicochemical characterizations
      with uniform particle size, high encapsulation efficacy and sustained release
      profile. In DNE-induced HCC mice treated with DOX/Cur-NPs, we observed decreased
      liver damage assessed by serum ALT and AST levels, liver/body weight ratio, and
      histopathological analysis. Compared with DOX-loaded nanoparticles (DOX-NPs),
      DOX/Cur-NPs induced increased Caspase-3 and Bax/Bcl-2 ratio, and decreased C-myc,
      PCNA and VEGF. The results revealed the synergistic effect of DOX/Cur-NPs on the
      apoptosis, proliferation and angiogenesis of HCC. The mRNA levels of MDR1, bcl-2
      and HIF-1alpha, and protein levels of P-gp, Bcl-2 and HIF-1alpha were decreased
      in DOX/Cur-NPs than those in DOX-NPs, indicating that Cur might reverse multidrug
      resistance (MDR) through these pathways. In HCC cells, enhanced cytotoxicity and
      decreased IC50 and resistant index further confirmed the synergistic effects of
      DOX/Cur-NPs than DOX-NPs. Our studies suggest that simultaneous delivery of DOX
      and Cur by DOX/Cur-NPs may be a promising treatment for HCC. 

PMID- 25770773
TI  - Infections with the tick-borne bacterium Candidatus Neoehrlichia mikurensis.
AB  - Candidatus Neoehrlichia mikurensis, which has rodents as its natural hosts, is an
      emerging tick-borne pathogen in Europe and Asia. This intracellular bacterium
      causes the infectious disease neoehrlichiosis. Immunocompromised patients may
      contract a severe form of neoehrlichiosis with high fever and
      vascular/thromboembolic events. As it is not detected with routine culture-based
      methods, neoehrlichiosis is underdiagnosed. 

PMID- 25770774
TI  - The compliance of clinicians and patients cannot be globalized.

PMID- 25770775
TI  - Pharmacokinetic and pharmacodynamic implications in inhalable antimicrobial
      therapy.
AB  - Inhaled antimicrobials provide a promising alternative to the systemically
      delivered drugs for the treatment of acute and chronic lung infections. The
      delivery of antimicrobials via inhalation route decreases the systemic exposure
      while increasing the local concentration in the lungs, enabling the use of
      antimicrobials with severe systemic side effects. The inhalation route of
      administration has several challenges in pharmacokinetic (PK) and pharmacodynamic
      (PD) assessments. This review discusses various issues that need to be considered
      during study, data analysis, and interpretation of PK and PD of inhaled
      antimicrobials. Advancements overcoming the challenges are also discussed. 

PMID- 25770776
TI  - Computational investigations of hERG channel blockers: New insights and current
      predictive models.
AB  - Identification of potential human Ether-a-go-go Related-Gene (hERG) potassium
      channel blockers is an essential part of the drug development and drug safety
      process in pharmaceutical industries or academic drug discovery centers, as they
      may lead to drug-induced QT prolongation, arrhythmia and Torsade de Pointes.
      Recent reports also suggest starting to address such issues at the hit selection
      stage. In order to prioritize molecules during the early drug discovery phase and
      to reduce the risk of drug attrition due to cardiotoxicity during pre-clinical
      and clinical stages, computational approaches have been developed to predict the
      potential hERG blockage of new drug candidates. In this review, we will describe
      the current in silico methods developed and applied to predict and to understand
      the mechanism of actions of hERG blockers, including ligand-based and structure
      based approaches. We then discuss ongoing research on other ion channels and hERG
      polymorphism susceptible to be involved in LQTS and how systemic approaches can
      help in the drug safety decision. 

PMID- 25770777
TI  - Cryptosporidiosis outbreak in a child day-care center caused by an unusual
      Cryptosporidium hominis subtype.
AB  - INTRODUCTION: This work describes the genetic characterization of Cryptosporidium
      and Giardia involved in an outbreak in a nursery school in Granada, Spain, that
      affected seven children under the age of 4. METHODS: Nucleic acids were extracted
      from the seven stool samples positive to Cryptosporidium or Giardia by microscopy
      and/or immunochromatography. The species and subtypes of Cryptosporidium were
      identified by PCR-RFLP and PCR of the SSUrRNA and gp60 genes, respectively. The
      assemblages of Giardia duodenalis isolates were characterized by PCR of the tpi
      gene. PCR products were sequenced and analyzed. RESULTS: All of the isolates were
      positive for Cryptosporidium hominis. Five of them belonged to subtype IaA11R2,
      one to subtype IbA10G2R2, and the other could not be identified. Three of these
      samples were positive for G. duodenalis by PCR, two belonging to the assemblage
      A, and the other one to assemblage B. DISCUSSION: This is the first report of
      Cryptosporidium hominis subtype IaA11R2 as a cause of an outbreak in Europe where
      subtype IbA10G2R2 is the most frequently identified. In the case of Giardia, an
      outbreak could not be confirmed because of the low number of positive samples and
      the low genetic variability of the amplified fragments for assemblage A of tpi
      gene. CONCLUSIONS: A new subtype, of Cryptosporidium hominis named IaA11R2, has
      been described as a cause of an outbreak in a nursery school in Granada, Spain.
      However an outbreak of giardiasis could not be confirmed.

PMID- 25770778
TI  - [Is necessary monitoring CD4 lymphocytes in HIV patients virologically stables?].

PMID- 25770779
TI  - Logic, probability, and human reasoning.
AB  - This review addresses the long-standing puzzle of how logic and probability fit
      together in human reasoning. Many cognitive scientists argue that conventional
      logic cannot underlie deductions, because it never requires valid conclusions to
      be withdrawn - not even if they are false; it treats conditional assertions
      implausibly; and it yields many vapid, although valid, conclusions. A new
      paradigm of probability logic allows conclusions to be withdrawn and treats
      conditionals more plausibly, although it does not address the problem of
      vapidity. The theory of mental models solves all of these problems. It explains
      how people reason about probabilities and postulates that the machinery for
      reasoning is itself probabilistic. Recent investigations accordingly suggest a
      way to integrate probability and deduction. 

PMID- 25770780
TI  - Product identification of non-reducing polyketide synthases with C-terminus
      methyltransferase domain from Talaromyces stipitatus using Aspergillus oryzae
      heterologous expression.
AB  - Talaromyces stipitatus ATCC 10500 possesses 17 non-reducing polyketide synthase
      (NR-PKS) genes. During the course of our functional analysis of PKS genes with a
      C-terminus methyltransferase domain from T. stipitatus, we expressed tspks2,
      tspks3 and tspks4 genes in the heterologous host Aspergillus oryzae,
      respectively. Although the tspks4 transformant gave no apparent product in HPLC
      analysis, a novel azaphilone pentaketide (3) was identified along with two known
      related products from the tspks2 transformant. Of four hexaketide products from
      the tspks3 transformant, two new compounds were identified to be 2-acetyl-7
      methyl-3,6,8-trihydroxynaphthalene (4) and its derivative fused with alpha-methyl
      alpha,beta-unsaturated gamma-lactone (7).

PMID- 25770781
TI  - Nanomolar inhibitors of Mycobacterium tuberculosis glutamine synthetase 1:
      synthesis, biological evaluation and X-ray crystallographic studies.
AB  - A series of imidazo[1,2-a]indeno[1,2-e]pyrazin-4-ones that potently inhibit M.
      tuberculosis glutamine synthetase (GlnA1) has been identified by high throughput
      screening. Exploration of this series was performed owing to a short chemistry
      program. Despite possibly nanomolar inhibitions, none of these compounds was
      active on whole cell Mtb, suggesting that GlnA1 may not be a suitable target to
      find new anti-tubercular drugs. 

PMID- 25770782
TI  - Evaluation of Aconitum diterpenoid alkaloids as antiproliferative agents.
AB  - Little information has been reported on the antitumor effects of the diterpenoid
      alkaloid constituents of Aconitum plants, used in the herbal drug 'bushi'. This
      study was aimed at determining the antitumor activities of Aconitum C19-and C20
      diterpenoid alkaloids and synthetic derivatives against lung (A549), prostate
      (DU145), nasopharyngeal (KB), and vincristine-resistant nasopharyngeal (KB-VIN)
      cancer cell lines. Newly synthesized C20-diterpenoid alkaloid derivatives showed
      substantial suppressive effects against all human tumor cell lines tested. In
      contrast, natural and derivatized C19-diterpenoid alkaloids showed only a slight
      or no effect. Most of the active compounds were hetisine-type C20-diterpenoid
      alkaloids, specifically kobusine and pseudokobusine analogs with two different
      substitution patterns, C-11 and C-11,15. Notably, several C20-diterpenoid
      alkaloids were more potent against multidrug-resistant KB subline KB-VIN cells.
      Pseudokobusine 11-3'-trifluoromethylbenzoate (94) is a possible promising new
      lead meriting additional evaluation against multidrug-resistant tumors. 

PMID- 25770784
TI  - Effectiveness of a psychological support program for relatives of people with
      mental disorders compared to a control group: a prandomized controlled trial.
AB  - Families of people affected by mental illness may suffer an adverse effect on
      well-being. In this study, the effectiveness of a cognitive-behavioral treatment
      designed for relatives of people with mental health problems was evaluated. The
      sample comprised 50 individuals: 30 in the experimental group, who completed
      assessment measures in pre-posttreatment and 6 months later, and 20 participants
      in the control group, who were assessed at baseline and 6 months later. In the
      experimental group, significant improvements in well-being were observed
      following the treatment and 6 months later, when compared to the control group,
      which did not demonstrate any significant changes in outcomes between the
      baseline and the second assessment 6 months later. This program has proven to be
      effective as a treatment for the relatives of people with mental disorders.
      Finally, several topics that may contribute to future research are discussed.

PMID- 25770783
TI  - BLM protein mitigates formaldehyde-induced genomic instability.
AB  - Formaldehyde is a reactive aldehyde that has been classified as a class I human
      carcinogen by the International Agency for Cancer Research. There are growing
      concerns over the possible adverse health effects related to the occupational and
      environmental human exposures to formaldehyde. Although formaldehyde-induced DNA
      and protein adducts have been identified, the genomic instability mechanisms and
      the cellular tolerance pathways associated with formaldehyde exposure are not
      fully characterized. This study specifically examines the role of a genome
      stability protein, Bloom (BLM) in limiting formaldehyde-induced cellular and
      genetic abnormalities. Here, we show that in the absence of BLM protein,
      formaldehyde-treated cells exhibited increased cellular sensitivity, an immediate
      cell cycle arrest, and an accumulation of chromosome radial structures. In
      addition, live-cell imaging experiments demonstrated that formaldehyde-treated
      cells are dependent on BLM for timely segregation of daughter cells. Both wild
      type and BLM-deficient formaldehyde-treated cells showed an accumulation of 53BP1
      and gammaH2AX foci indicative of DNA double-strand breaks (DSBs); however,
      relative to wild-type cells, the BLM-deficient cells exhibited delayed repair of
      formaldehyde-induced DSBs. In response to formaldehyde exposure, we observed co
      localization of 53BP1 and BLM foci at the DSB repair site, where ATM-dependent
      accumulation of formaldehyde-induced BLM foci occurred after the recruitment of
      53BP1. Together, these findings highlight the significance of functional
      interactions among ATM, 53BP1, and BLM proteins as responders associated with the
      repair and tolerance mechanisms induced by formaldehyde. 

PMID- 25770785
TI  - An extended cost-effectiveness analysis of publicly financed HPV vaccination to
      prevent cervical cancer in China.
AB  - INTRODUCTION: Cervical cancer screening and existing health insurance schemes in
      China fall short of reaching women with prevention and treatment services,
      especially in rural areas where the disease burden is greatest. We conducted an
      extended cost-effectiveness analysis (ECEA) to evaluate public financing of HPV
      vaccination to prevent cervical cancer, adding new dimensions to conventional
      cost-effectiveness analysis through an explicit inclusion of equity and impact on
      financial risk protection. METHODS: We synthesized available epidemiological,
      clinical, and economic data from China using an individual-based Monte Carlo
      simulation model of cervical cancer to estimate the distribution of deaths
      averted by income quintile, comparing vaccination plus screening against current
      practice. We also estimated reductions in cervical cancer incidence, net costs to
      the government (HPV vaccination costs minus cervical cancer treatment costs
      averted), and patient cost savings, as well as the incremental government health
      care costs per death averted. RESULTS: HPV vaccination is cost-effective across
      all income groups when the cost is less than US $50 per vaccinated girl. Compared
      to screening alone, adding preadolescent HPV vaccination followed by cervical
      cancer screening in adulthood could reduce cancer by 44 percent across all income
      groups, while providing relatively higher financial protection to the poorest
      women. The absolute numbers of cervical cancer deaths averted and the financial
      risk protection from HPV vaccination are highest among women in the lowest
      quintile; women in the bottom income quintiles received higher benefits than
      those in the upper wealth quintiles. Patient cost savings represent a large
      proportion of poor women's average per capita income, reaching 60 percent among
      women in the bottom income quintile and declining to 15 percent among women in
      the wealthiest quintile.

PMID- 25770787
TI  - Prognostic indicators after cardiac surgery in children and their relationship
      with the oxidative stress response.
AB  - OBJECTIVES: To analyse the trend in lipid peroxidation and antioxidant response
      as key markers of oxidative stress after paediatric cardiovascular surgery, and
      compare them with other internationally accepted clinical prognostic indicators.
      PATIENTS AND METHODS: A prospective study was conducted on 30 children aged one
      month to 14 years, weight>5 kg, undergoing cardiopulmonary bypass surgery. Blood
      samples were taken just before the intervention, immediately after surgery, and
      after 18-20 h. Cell membrane lipid peroxidation was analysed by quantifying
      malondialdehyde, as well as measuring total glutathione (oxidized and reduced),
      as representatives of antioxidant response. An analysis was also performed on
      clinical variables for establishing a score for the systemic inflammatory
      response syndrome associated with cardiopulmonary bypass. RESULTS: The study
      included 30 children with a mean age of 4.1 years old (interquartile range [IQR]:
      2.7; 8.0). Of these, 62.1% were girls. The standard deviation of the median
      weight was -0.39 (IQR: -0.76; 0.24), the median height was -0.22 (IQR: -0.74;
      0.27), and the median BMI was -0.43 (IQR: -1; 0.45). The final surgery times were
      divided into 2 parts: total time of extracorporeal circulation, with a mean of 79
      min (IQR: 52.5; 125.5), and the clamping time, a measurement included in the
      previous figure with a mean value of 38.5 min (IQR: 22; 59). Malondialdehyde
      increased and glutathione decreased in postoperative time, with clear,
      statistically significant direct correlation between time of extracorporeal
      circulation and percentage decrease in total glutathione between preoperative and
      immediate postoperative time, and a decline between the preoperative and late
      postoperative. There was a statistical correlation between total glutathione
      levels at 18-20 h postoperatively and the duration of mechanical ventilation and
      inflammatory systemic response syndrome. CONCLUSIONS: Surgery with extracorporeal
      circulation performed in children activates inflammatory mediators, being maximum
      after aortic clamping, and improving after the first 24h. The level of oxidative
      stress activation depends on surgical times. The development of systemic
      inflammatory response syndrome is associated with longer duration of mechanical
      ventilation, longer stay in intensive care, higher scores in the Aristotle model
      and longer surgical times. Those who do not meet criteria for inflammatory
      response have higher levels of glutathione in first 24h.

PMID- 25770786
TI  - A microneedle patch containing measles vaccine is immunogenic in non-human
      primates.
AB  - Very high vaccination coverage is required to eliminate measles, but achieving
      high coverage can be constrained by the logistical challenges associated with
      subcutaneous injection. To simplify the logistics of vaccine delivery, a patch
      containing micron-scale polymeric needles was formulated to encapsulate the
      standard dose of measles vaccine (1000 TCID50) and the immunogenicity of the
      microneedle patch was compared with subcutaneous injection in rhesus macaques.
      The microneedle patch was administered without reconstitution with diluent,
      dissolved in skin within 10 min, and caused only mild, transient skin erythema.
      Both groups of rhesus macaques generated neutralizing antibody responses to
      measles that were consistent with protection and the neutralizing antibody titers
      were equivalent. In addition, the microneedle patches maintained an acceptable
      level of potency after storage at elevated temperature suggesting improved
      thermostability compared to standard lyophilized vaccine. In conclusion, a
      measles microneedle patch vaccine was immunogenic in non-human primates, and this
      approach offers a promising delivery method that could help increase vaccination
      coverage.

PMID- 25770788
TI  - Liquid-liquid extraction and liquid chromatography-mass spectrometry detection of
      curcuminoids from bacterial culture medium.
AB  - Liquid chromatography-mass spectrometry (LC-MS) has been used to detect
      polyphenolic curcuminoids found in turmeric but studies of metabolism by
      bacterial and mammalian cells in vitro are compromised by poor recovery from the
      culture medium. We report a liquid-liquid extraction procedure with ethyl acetate
      and use LC-MS to quantify extracted curcuminoids. Ethyl acetate allows recoveries
      of ~ 80-86% of curcuminoids from the bacterial growth medium, bacterial cell
      lysate and combined bacterial cell and growth medium matrices; a clear
      improvement over acetonitrile where recoveries were ~ 25-66%. This optimised
      method will enable studies of curcuminoid metabolism and may be applicable to
      other hydrophobic polyphenolic compounds.

PMID- 25770789
TI  - Relative quantification of albumin and fibrinogen modifications by liquid
      chromatography tandem mass spectrometry in the diagnosis and monitoring of acute
      pancreatitis.
AB  - The increasing availability of liquid chromatography tandem mass spectrometry (LC
      MS/MS) in clinical laboratories provides the opportunity to replace or complement
      present underperforming immuno- and chemometric assays. Amylase and lipase show
      limited specificity and sensitivity for pancreatic inflammation and lack the
      capacity of monitoring the disease due to their short half-lives. Previous
      findings suggested that cleavage products of the pancreatic enzyme
      carboxypeptidase A could be a more suitable indicator for defining and
      classifying pancreatic inflammation. The plasma proteins albumin and beta
      fibrinogen were digested with trypsin and truncated forms (des-Leu-albumin, and
      des-Gln-beta-fibrinogen) quantified against their non-truncated forms by LC
      MS/MS. Four hundred fifty eight samples from 83 patients were used to evaluate
      the novel method and affirm its suitability for detecting acute pancreatitis. A
      robust, selective, precise and accurate LC-MS/MS method was set up to measure the
      proportion of truncated proteins. Reference ranges for the proportion of the
      truncated albumin and beta-fibrinogen were from 2% to 9% and 3% to 25%,
      respectively. Acute pancreatitis patients had values above these ranges and were
      distinctly separated from reference control individuals. The longer circulating
      half-lives of albumin and fibrinogen compared to pancreatic enzymes themselves
      provide the potential to diagnose pancreatitis more specifically over a longer
      time period, to monitor the course of the disease, and to track recurrent
      complications. The wide range of the proportion and the differential half-life of
      both truncated proteins could also be used for assessing the severity of
      pancreatitis. 

PMID- 25770790
TI  - Separation and purification of four oligostilbenes from Iris lactea Pall. var.
      chinensis (Fisch.) Koidz by high-speed counter-current chromatography.
AB  - A method of using high-speed counter-current chromatography (HSCCC) for
      preparative isolation and purification of oligostilbenes from the ethanol
      extracts of seed kernel of Iris lactea Pall. var. chinensis (Fisch.) Koidz was
      established in this study. Four oligostilbenes were successfully separated and
      purified by HSCCC with two sets of two-phase solvent system, n-hexane-ethyl
      acetate-methanol-water (3:6:4.2:5.5, v/v/v/v) in the head-to-tail elution mode
      for the first separation to mainly isolate vitisin A (58 mg), E-viniferin (76 mg)
      and peak II (43 mg) from 300 mg of the crude ethanol extracts, and then light
      petroleum-ethyl acetate-methanol-water (5:5:3:6, v/v/v/v) in the tail-to-head
      elution mode for the second separation to isolate vitisin B (52 mg) and vitisin C
      (11 mg) from 100mg of peak II. The purities of the isolated four oligostilbenes
      were all over 95.0% as determined by HPLC. Vitisin A, vitisin B and vitisin C,
      resveratrol tetramers, were isolated from Iris lactea for the first time. The
      preparation of crude sample was simple and the HSCCC method for the isolation and
      purification of four oligostilbenes was rapid, efficient and economical.

PMID- 25770792
TI  - Return to duty after severe bilateral lower extremity trauma.
AB  - Despite the preponderance of evidence demonstrating poor outcomes as a result of
      combat-related orthopaedic trauma, teams of medical professionals have remained
      undaunted in their pursuit of innovative techniques to maximize the functional
      capacity of Servicemembers with devastating extremity injuries. We present the
      case of an Active Duty Special Forces (SF) qualified senior noncommissioned
      officer (NCO) with severely injured extremities successfully salvaged with a
      multidisciplinary program involving cutting-edge prosthetic technology and a
      novel approach to physical rehabilitation. 

PMID- 25770791
TI  - Determination of depression biomarkers in rat plasma by liquid chromatography
      mass spectrometry for the study of the antidepressant effect of Zhi-Zi-Hou-Po
      decoction on rat model of chronic unpredictable mild stress.
AB  - Zhi-Zi-Hou-Po decoction (ZZHPD), a traditional Chinese medicine (TCM) formula,
      has been used for treatment of depressive-like symptoms for centuries. However,
      studies of its antidepressant effect and mechanism are challenging, owing to the
      complex pathophysiology of depression and complexity of ZZHPD with multiple
      constituents acting on different metabolic pathways. The present study was
      designed to develop a liquid chromatography-mass spectrometry (LC-MS) method for
      simultaneous determination of depression biomarkers: tryptophan (Trp),
      phenylalanine (Phe), tyrosine (Tyr), indole-3-acetic acid (IAA), hippuric acid
      (HA), phenaceturic acid (PA), creatinine (Cr), glutamic acid (Glu), succinic acid
      (SA) and gamma-aminobutyric acid (GABA), as well as to study the antidepressant
      effect and potential mechanism of ZZHPD based on holistic view of an organism.
      The analysis was performed on a CAPCELL PAK C18 column with methanol and 0.01%
      formic acid in water using gradient elution. The method showed a good linearity
      (r(2)>0.99) with the other validation parameters were within acceptance range.
      The results demonstrated Trp, Phe, Tyr, IAA, HA, Cr, Glu and SA levels were
      significant lower in model group, while PA and GABA were significant higher than
      those in control group. The rats with ZZHPD treatment showed a tendency of
      bringing the levels of all these biomarkers to normal except Cr and Glu. It could
      be a powerful manner to provide mechanistic insights into the therapeutic effects
      of complex prescriptions and further understand pathophysiology of depression to
      assist in clinical diagnosis. 

PMID- 25770793
TI  - Special Operations Soldier With Cardiac Family History: Use of CCTA and Protein
      Biomarker Testing to Detect Risk of Heart Attack From Noncalcified Plaque.
AB  - OBJECTIVE: We sought to characterize the risk of a heart attack in a 48-year-old
      asymptomatic US Special Operations Command (SOCOM) Soldier without known coronary
      artery disease (CAD). BACKGROUND: CAD continues to be a leading cause of
      morbidity and mortality among most age groups in the United States. Much research
      is dedicated to establishing new techniques to predict myocardial infarction
      (MI). METHODS: Coronary computed tomography (CT) angiography, also known as CCTA,
      along with 7-protein serum biomarker risk assessment was performed for risk
      evaluation. RESULTS: A 48-year-old SOCOM Soldier with a family history of heart
      disease had skeletal chest pain from war injuries and a 5-fold higher risk of
      heart attack over the next 5 years on the basis of protein markers. A
      nonobstructive left anterior descending coronary artery (LAD) plaque with a lipid
      rich core and a thin fibrous cap (i.e., vulnerable plaque) was detected by CCTA.
      The patient was warned about his risk and prescribed four cardiac medications and
      scheduled for angioplasty even though he fell outside the guidelines by not
      having a severe obstructive blockage. Four days later, unfortunately, he had a
      heart attack before starting his medications and before angioplasty. CONCLUSION:
      CCTA with biomarker testing may have an important role in predicating acute
      coronary syndrome (ACS) in Special Operations Forces (SOF) Soldiers with at least
      one risk factor. Conventional stress testing and nuclear scanning would not
      detect non-flow-limiting vulnerable plaques in vulnerable patients. In order to
      collect more data, the PROTECT Registry has been started to evaluate asymptomatic
      Soldiers with at least one risk factor referred to the clinic by military
      physicians.

PMID- 25770794
TI  - Decompression sickness following altitude-chamber training.
AB  - Decompression sickness (DCS) is one of several dysbarisms (medical conditions
      resulting from a change in atmospheric pressure) that can be encountered by the
      Special Operations Forces (SOF) medical provider. DCS can present with several
      different manifestations. The authors present the case of a 23-year-old Airman
      who presented with vague neurologic symptoms following altitude-chamber training.
      They discuss the care of casualties with DCS and its implications for SOF. 

PMID- 25770795
TI  - Optimizing the Use of Limb Tourniquets in Tactical Combat Casualty Care: TCCC
      Guidelines Change 14-02.

PMID- 25770796
TI  - Laboratory testing of emergency tourniquets exposed to prolonged heat.
AB  - BACKGROUND: Environmental exposure of tourniquets has been associated with
      component damage rates, but the specific type of environmental exposure, such as
      heat, is unknown. Emergency-tourniquet damage has been associated with
      malfunction and loss of hemorrhage control, which may risk loss of life during
      first aid. The purposes of the study are to determine the damage rate of
      tourniquets exposed to heat and to compare the rate to that of controls. METHODS:
      Three tourniquet models (Combat Application Tourniquet((r)); SOF((r)) Tactical
      Tourniquet; Ratcheting Medical Tourniquet((r))) were tested using a manikin
      (HapMed Leg Tourniquet Trainer; www.chisystems.com) that simulates extremity
      hemorrhage. The study group of 15 tourniquets (five devices per model, three
      models) was exposed to heat (oven at 54.4 degrees  C [130 degrees  F] for 91
      days), and 15 tourniquets similarly constituted the control group (unexposed to
      heat). Damage, hemorrhage control, distal pulse stoppage, time to effectiveness,
      pressure (mmHg), and blood loss volumes were measured. RESULTS: Three tourniquets
      in both groups had damage not associated with heat exposure (p = 1). Heat
      exposure was not associated with change in effectiveness rates (p = .32); this
      lack of association applied to both hemorrhage control and pulse stoppage. When
      adjusted for the effects of user and model, the comparisons of time to
      effectiveness and total blood loss were statistically significant (p < .0001),
      but the comparison of pressure was not (p = .0613). CONCLUSION: Heat exposure was
      not associated with tourniquet damage, inability to gain hemorrhage control, or
      inability to stop the distal pulse.

PMID- 25770797
TI  - Initial tourniquet pressure does not affect tourniquet arterial occlusion
      pressure.
AB  - BACKGROUND: Effective nonelastic strap-based tourniquets are typically pulled
      tight and friction or hook-and-loop secured before engaging a mechanical
      advantage system to reach arterial occlusion pressure. This study examined the
      effects of skin surface initial secured pressure (Friction Pressure) on the skin
      surface pressure applied at arterial occlusion (Occlusion Pressure) and on the
      use of the mechanical advantage system. METHODS: Combat Application
      Tourniquets((r)) (CATs; combattourniquet.com) and Tactical Ratcheting Medical
      Tourniquets (RMTs; www .ratchetingbuckles.com) were applied to 12 recipient
      thighs with starting Friction Pressures of 25 (RMT only), 50, 75, 100, 125, 150,
      175 (CAT only), and 200mmHg (CAT only). The CAT strap was single threaded.
      Pressure was measured with an air-filled, size #1, neonatal blood pressure cuff
      under the Base (CAT), Ladder (RMT), and Strap (CAT and RMT) of each 3.8cm-wide
      tourniquet. RESULTS: Base or Ladder pressure and Strap pressure were related but
      increasingly different at increasing pressures, with Strap pressures being lower
      (Friction Pressure, r > 0.91; Occlusion Pressure, r > 0.60). Friction Pressure
      did not affect Occlusion Pressure for either design. Across the 12 thighs, the
      correlation coefficient for Strap Friction Pressure versus CAT windlass turns was
      r = -0.91 +/- 0.04, and versus RMT ladder distance traveled was r = -0.94 +/-
      0.06. Friction Pressures of 150mmHg or greater were required to achieve CAT
      Occlusion with two or fewer windlass turns. CAT and RMT Strap Occlusion Pressures
      were similar on each recipient (median, minimum - maximum; CAT: 318mmHg, 260 -
      536mmHg; RMT: 328mmHg, 160 - 472mmHg). CONCLUSIONS: Achieving high initial strap
      tension is desirable to minimize windlass turns or ratcheting buckle travel
      distance required to reach arterial occlusion, but does not affect tourniquet
      surface-applied pressure needed for arterial occlusion. For same-width,
      nonelastic strap-based tourniquets, differences in the mechanical advantage
      system may be unimportant to final tourniquet-applied pressure needed for
      arterial occlusion.

PMID- 25770798
TI  - Blood flow restriction rehabilitation for extremity weakness: a case series.
AB  - BACKGROUND: Blood flow restricted (BFR) training, the brief and partial
      restriction of venous outflow of an extremity during low load resistance
      exercises, is a safe and effective method of improving strength in healthy,
      active individuals. A relatively unexplored potential of this adjunctive modality
      lies in treating patients with severe musculoskeletal trauma, persistent chronic
      quadriceps and hamstring weakness despite traditional therapy, and low
      improvement during early postoperative strengthening. METHODS: This case series
      describes patients with chronic quadriceps and hamstring weakness who received an
      intervention of BFR at low loads, 20% of 1 repetition max (1RM), to restore
      strength. A case series was conducted of seven patients, all located at one
      hospital and all with traumatic lower extremity injuries. The seven patients were
      treated at the same medical center and with the same BFR protocol. All seven
      patients had isokinetic dynamometer testing that showed persistent thigh muscle
      weakness despite previous rehabilitation with traditional therapy and 35% to 75%
      peak torque deficit in either knee extension or flexion compared with the
      contralateral lower extremity. Patients underwent 2 weeks of BFR training therapy
      using a pneumatic tourniquet set at 110mmHg while performing leg extensions, leg
      presses, and reverse leg presses. All affected extremities were retested after 2
      weeks (six treatment sessions). Dynamometer measurements were done with flexion
      and extension at two speeds: 90 degrees  and 300 degrees /sec. The data recorded
      included peak torque normalized for body weight, average power, and total work.
      RESULTS: All seven patients demonstrated improvements in peak torque, average
      power, and total work for both knee flexion and extension, with power being the
      most improved overall. Peak torque improved an average of 13% to 37%, depending
      on contraction direction and speed. Average power improved an average of 42% to
      81%, and total work improved an average of 35% to 55%. CONCLUSION: BFR therapy at
      low loads can affect improvement in muscle strength in patients who are unable to
      perform high-resistance exercise or patients who have persistent extremity
      weakness despite traditional therapy.

PMID- 25770799
TI  - The Effects of Movement on Hemorrhage When QuikClot(r) Combat GauzeTM Is Used in
      a Hypothermic Hemodiluted Porcine Model.
AB  - BACKGROUND: The purpose of this study was to compare the effectiveness of
      QuikClot((r)) Combat GauzeTM (QCG) to a control wound dressing to withstand
      movement in a porcine model with hemodilution and hypothermia. DESIGN: This was a
      prospective study with a between-subjects experimental design. Twenty-six
      Yorkshire swine were randomly assigned to two groups: QCG (n = 13) or a control
      dressing (n = 13). METHODS: The subjects were exsanguinated to 30% of the blood
      volume; hypothermia was induced for 10 minutes. The hemostatic agent, QCG, was
      placed into the wound, followed by standard wound packing. If hemostasis was
      achieved, 5L of crystalloid solution were rapidly administered intravenously, and
      the wound was again observed for rebleeding. If no bleeding occurred, the
      extremity on the side of the injury was systematically moved through flexion,
      extension, abduction, and adduction sequentially 10 times or until rebleeding
      occurred. RESULTS: An independent t test indicated there were significant
      differences in the number of movements before rebleeding between the QCG group
      (mean +/- standard deviation [SD], 32.92 +/- 14.062) and the control group (mean
      +/- SD, 6.15 +/- 15.021) (p < .0001). CONCLUSION: QCG produces a robust clot that
      can withstand more movement than a control dressing.

PMID- 25770800
TI  - Review, clinical update, and practice guidelines for excited delirium syndrome.
AB  - Excited delirium syndrome (ExDS) is a term used to describe patients experiencing
      a clinical condition characterized by bizarre and aggressive behavior, often in
      association with the use of chronic sympathomimetic drug abuse. The agitated and
      disruptive behavior of persons with ExDS often results in a call to police
      resulting in an arrest for disorderly conduct. The suspect's inability to comply
      with police commands during the arrest frequently results in a struggle and the
      use of physical or chemical control measures, including the use of conductive
      energy weapons (CEWs). Deaths from this hypermetabolic syndrome are infrequent
      but potentially preventable with early identification, a coordinated aggressive
      police intervention, and prompt medical care. Preliminary experiences suggest
      that ExDS is a medical emergency treated most effectively using a coordinated
      response between police officers and emergency medical providers. Once the person
      suspected of experiencing ExDS is in custody, medical providers should rapidly
      sedate noncompliant patients with medications such as ketamine or an
      antipsychotic drug such as haloperidol in combination with a benzodiazepine drug
      such as midazolam or diazepam. Once sedated, patients should undergo a screening
      medical assessment and undergo initial treatment for conditions such as
      hyperthermia and dehydration. All patients exhibiting signs of ExDS should be
      transported rapidly to a medical treatment facility for further evaluation and
      treatment. This article reviews the epidemiology, clinical presentation,
      diagnosis, and treatment options for ExDS. 

PMID- 25770801
TI  - Operational Point-of-Care Ultrasound Review: Low-Cost Simulators and Resources
      for Advanced Prehospital Providers.
AB  - Prehospital ultrasound use is a relatively new skill set. The military noted the
      clear advantages of this skill set in the deployed setting and moved forward with
      teaching their advanced combat trauma medics skills to perform specific
      examinations. The training curriculum for Special Operations-level clinical
      ultrasound was created and adapted from training guidelines set forth by the
      American College of Emergency Physicians with a focus on the examinations
      relevant to the Special Operations community. Once providers leave the training
      environment, skill sustainment can be difficult. We discuss the relevant
      ultrasound exams for the prehospital setting. We address opportunities to improve
      point-of-care ultrasound skills through hands-on experience while in a fixed
      medical facility. Options for simulation-based training are discussed with
      descriptions for creating low-cost simulation models. Finally, a list of online
      resources is provided to review specific ultrasound examinations. 

PMID- 25770802
TI  - A study of prehospital medical documentation by military medical providers during
      precombat training.
AB  - Documentation of medical care provided is paramount for improving performance and
      ultimately reducing morbidity and mortality. However, documentation of
      prehospital trauma care on the battlefield has historically been suboptimal.
      Modernization of prehospital documentation tools have aligned data and
      information to be gathered with up-to-date treatment being rendered through
      Tactical Combat Casualty Care (TCCC) protocols and practices. Our study was
      conducted to evaluate TCCC Card completion, and accuracy of card completion, by
      military medical providers conducting precombat training through the Tactical
      Combat Medical Care Course. Study results do not show a deficiency in TCCC
      documentation training as provided by this course which should translate to
      adequate ability to accurately document prehospital trauma care on the
      battlefield. Leadership emphasis and community acceptance is required to increase
      compliance with prehospital documentation. 

PMID- 25770803
TI  - Battlefield Analgesia: TCCC Guidelines Are Not Being Followed.
AB  - BACKGROUND: Servicemembers injured in combat often experience moderate to severe
      acute pain. Early and effective pain control in the prehospital setting has been
      shown to reduce the sequelae of untreated pain. Current data suggest that lack of
      point-of-injury (POI) analgesia has significant, downstream effects on healthcare
      quality and associated costs. METHODS: This was a process improvement project to
      determine the current rate of adherence to existing prehospital pain management
      guidelines. The records of patients who had sustained a major injury and met
      current Tactical Combat Casualty Care (TCCC) criteria for POI analgesia from July
      2013 through March 2014 were reviewed to determine if pain medication was given
      in accordance with existing guidelines, including medication administration and
      routes. On 31 October 2013, the new TCCC guidelines were released. The "before"
      period was from July 2013 through October 2013. The "after" period was from
      November 2013 through March 2014. RESULTS: During the project period, there were
      185 records available for review, with 135 meeting TCCC criteria for POI
      analgesia (68 pre-, 66 postintervention). Prior to 31 October 2013, 17% of study
      patients received analgesia within guidelines at the POI compared with 35% in the
      after period. The most common medication administered pre-and post-release was
      oral transmucosal fentanyl citrate. Special Operations Forces had higher
      adherence rates to TCCC analgesia guidelines than conventional forces, but these
      still were low. CONCLUSION: Less than half of all eligible combat casualties
      receive any analgesia at the POI. Further research is needed to determine the
      etiology of such poor adherence to current TCCC guidelines.

PMID- 25770804
TI  - Only break glass in case of war?

PMID- 25770805
TI  - Mindfulness: a fundamental skill for performance sustainment and enhancement.
AB  - The term "mindfulness" has become very fashionable within the military and across
      multiple sectors of civilian and first responder populations. Overall, the key
      concept of mindfulness is intentionally being acutely aware of what is going on
      internally as well as externally, without reacting. Mindfulness and the awareness
      that underlies it are inherent capabilities that can be honed through training.
      As such, classes in mindfulness are being offered in many venues and medical
      clinics are using mindfulness-based interventions for patients for a wide range
      of medical issues. The evidence behind the benefits of mindfulness is extensive
      and instructive. Importantly, evidence suggests that mindfulness can be helpful
      for many operational, leadership, and personal activities and is likely
      beneficial for enhancing resilience and overall health. Many current military
      leaders are using mindfulness as a tool to better prepare for a dynamic and
      uncertain future. 

PMID- 25770806
TI  - Staphylococcus sciuri: An Entomological Case Study and a Brief Review of the
      Literature.
AB  - Staphylococcus sciuri is an emerging gram-positive bacterial pathogen that is
      infrequently isolated from cases of human disease. This organism is capable of
      rapid conversion from a state of methicillin sensitivity to a state of
      methicillin resistance and has been shown to express a set of highly effective
      virulence factors. The antibiotic-resistance breakpoints of S. sciuri differ
      significantly from the more common Staphylococcus species. Therefore, the rapid
      identification of S. sciuri in clinical material is a prerequisite for the proper
      determination of the antibiotic-resistance profile and the rapid initiation of
      antimicrobial therapy. Here, we present a brief literature review of S. sciuri
      and an entomological case study in which we describe the colonization of an
      American cockroach with this agent. In addition, we discuss potential
      implications for the distribution and evolution of antibiotic-resistant members
      of the genus Staphylococcus. 

PMID- 25770807
TI  - MEDCAN-GRO: Medical Capacity for African Nations - Growing Regional Operability A
      Case Study in Special Operations Forces Capacity Building.
AB  - Medical Capacity for African Nations-Growing Regional Operability (MEDCAN-GRO) is
      a framework for addressing healthcare engagements that are intended to provide
      sustainable capacity building with partner nations. MEDCAN-GRO provides SOF units
      with a model that can be scaled to partner nation needs and aligned with the
      goals of the TSOC in an effort to enhance partner nation security. 

PMID- 25770808
TI  - A painful rash in an austere environment.
AB  - Dermatologic complaints are common in the deployed environment. Preventive
      medicine and knowledge of indigenous flora and fauna are cornerstones for forward
      deployed medical personnel. This article describes a case of Paederus dermatitis
      in an austere environment, reviews dermatologic terminology, and provides a
      reminder of the importance of exercising good preventive medicine procedures. 

PMID- 25770809
TI  - Abdominal pain.
AB  - The series objective is to review various clinical conditions/presentations,
      including the latest evidence on management, and to dispel common myths. In the
      process, core knowledge and management principles are enhanced. A clinical case
      will be presented. Cases will be drawn from real life but phrased in a context
      that is applicable to the Special Operations Forces (SOF) or tactical emergency
      medical support (TEMS) environment. Details will be presented in such a way that
      the reader can follow along and identify how they would manage the case
      clinically depending on their experience and environment situation. Commentary
      will be provided by currently serving military medical technicians. The medics
      and author will draw on their SOF experience to communicate relevant clinical
      concepts pertinent to different operational environments including SOF and TEMS.
      Commentary and input from active special operations medical technicians will be
      part of the feature. 

PMID- 25770810
TI  - The importance of physical fitness for injury prevention: part 1.
AB  - Physical fitness can be defined as a set of attributes that allows the ability to
      perform physical activity. The attributes or components of fitness were
      identified by testing large numbers of individuals on physical performance tests
      (e.g., sit-ups, push-ups, runs, pull-ups, rope climbs, vertical jump, long
      jumps), and using statistical techniques to find tests that seem to share common
      performance requirements. These studies identified strength, muscular endurance,
      cardiorespiratory endurance, coordination, balance, flexibility, and body
      composition as important fitness components. Military studies have clearly shown
      that individuals with lower levels of cardiorespiratory endurance or muscular
      endurance are more likely to be injured and that improving fitness lowers injury
      risk. Those who are more fit perform activity at a lower percentage of their
      maximal capability and so can perform the task for a longer period of time,
      fatigue less rapidly, recover faster, and have greater reserve capacity for
      subsequent tasks. Fatigue alters movement patterns, putting stress on parts of
      the body unaccustomed to it, possibly increasing the likelihood of injury.
      Soldiers should develop and maintain high levels of physical fitness, not only
      for optimal performance of occupational tasks but also to reduce injury risk. 

PMID- 25770811
TI  - Cutaneous leishmaniasis.
AB  - Cutaneous leishmaniasis is the most common form of leishmaniasis, which also
      appears in mucosal and visceral forms. It is a disease found worldwide, caused by
      an intracellular protozoan parasite of which there are more than 20 different
      species. The disease is transmitted by the bite of an infected, female,
      phlebotomine sand fly, causing skin lesions that can appear weeks to years after
      a bite. A typical lesion will start out in a papular form, progressing to a
      nodular plaque and, eventually, to a persistent ulcerative lesion. Special
      Operations Forces medical providers should be aware of this disease, which must
      be in the differential diagnosis of a patient who has lived in endemic areas and
      who has a persistent skin lesion nonresponsive to typical therapies. 

PMID- 25770812
TI  - Wasting away?

PMID- 25770814
TI  - Aprepitant for the prevention of chemotherapy-induced nausea and vomiting in
      children: a randomised, double-blind, phase 3 trial.
AB  - BACKGROUND: Oral aprepitant, a neurokinin-1 receptor antagonist, is recommended
      in combination with other anti-emetic agents for the prevention of nausea and
      vomiting associated with moderately or highly emetogenic chemotherapy in adults,
      but its efficacy and safety in paediatric patients are unknown. We did this phase
      3 trial to examine the safety and efficacy of such treatment in children.
      METHODS: In this final analysis of a phase 3, randomised, multicentre, double
      blind study, patients aged 6 months to 17 years with a documented malignancy who
      were scheduled to receive either moderately or highly emetogenic chemotherapy
      were randomly assigned with an interactive voice response system to an age-based
      and weight-based blinded regimen of aprepitant (125 mg for ages 12-17 years; 3.0
      mg/kg up to 125 mg for ages 6 months to <12 years) plus ondansetron on day 1,
      followed by aprepitant (80 mg for ages 12-17 years; 2.0 mg/kg up to 80 mg for
      ages 6 months to <12 years) on days 2 and 3, or placebo plus ondansetron on day 1
      followed by placebo on days 2 and 3; addition of dexamethasone was allowed.
      Randomisation was stratified according to patient age, planned use of
      chemotherapy associated with very high risk of emetogenicity, and planned use of
      dexamethasone as an anti-emetic. Ondansetron was dosed per the product label for
      paediatric use or local standard of care. The primary efficacy endpoint was the
      proportion of patients who achieved complete response (defined as no vomiting, no
      retching, and no use of rescue medication) during the 25-120 h (delayed phase)
      after initiation of emetogenic chemotherapy. Efficacy and safety analyses were
      done with all randomly assigned patients who received at least one dose of study
      treatment. This study is registered with ClinicalTrials.gov, number NCT01362530.
      FINDINGS: Between Sept 22, 2011, and Aug 16, 2013, 307 patients were randomly
      assigned at 49 sites in 24 countries to either the aprepitant group (155
      patients) or to the control group (152 patients). Three patients in the
      aprepitant group and two in the control group did not receive study medication,
      and thus were excluded from analyses. 77 (51%) of 152 patients in the aprepitant
      group and 39 (26%) of 150 in the control group achieved a complete response in
      the delayed phase (p<0.0001). The most common grade 3-4 adverse events were
      febrile neutropenia (23 [15%] of 152 in the aprepitant group vs 21 [14%] of 150
      in the control group), anaemia (14 [9%] vs 26 [17%]), and decreased neutrophil
      count (11 [7%] vs 17 [11%]). The most common serious adverse event was febrile
      neutropenia (23 [15%] patients in the aprepitant group vs 22 [15%] in the control
      group). INTERPRETATION: Addition of aprepitant to ondansetron with or without
      dexamethasone is effective for the prevention of chemotherapy-induced nausea and
      vomiting in paediatric patients being treated with moderately or highly
      emetogenic chemotherapy. FUNDING: Merck & Co., Inc.

PMID- 25770815
TI  - Anti-emetics in paediatric patients receiving chemotherapy.

PMID- 25770817
TI  - Stem cell-paved biobridges facilitate stem transplant and host brain cell
      interactions for stroke therapy.
AB  - Distinguished by an infarct core encased within a penumbra, stroke remains a
      primary source of mortality within the United States. While our scientific
      knowledge regarding the pathology of stroke continues to improve, clinical
      treatment options for patients suffering from stroke are extremely limited.
      Tissue plasminogen activator (tPA) remains the sole FDA-approved drug proven to
      be helpful following stroke. However, due to the need to administer the drug
      within 4.5h of stroke onset its usefulness is constrained to less than 5% of all
      patients suffering from ischemic stroke. One experimental therapy for the
      treatment of stroke involves the utilization of stem cells. Stem cell
      transplantation has been linked to therapeutic benefit by means of cell
      replacement and release of growth factors; however the precise means by which
      this is accomplished has not yet been clearly delineated. Using a traumatic brain
      injury model, we recently demonstrated the ability of transplanted mesenchymal
      stromal cells (MSCs) to form a biobridge connecting the area of injury to the
      neurogenic niche within the brain. We hypothesize that MSCs may also have the
      capacity to create a similar biobridge following stroke; thereby forming a
      conduit between the neurogenic niche and the stroke core and peri-infarct area.
      We propose that this biobridge could assist and promote interaction of host brain
      cells with transplanted stem cells and offer more opportunities to enhance the
      effectiveness of stem cell therapy in stroke. This article is part of a Special
      Issue entitled SI: Cell Interactions In Stroke. 

PMID- 25770816
TI  - Collaterals: Implications in cerebral ischemic diseases and therapeutic
      interventions.
AB  - Despite the tremendous progress made in the treatment of cerebrovascular
      occlusive diseases, many patients suffering from ischemic brain injury still
      experience dismal outcomes. Although rehabilitation contributes to post-stroke
      functional recovery, there is no doubt that interventions that promote the
      restoration of blood supply are proven to minimize ischemic injury and improve
      recovery. In response to the acutely decreased blood perfusion during arterial
      occlusion, arteriogenesis, the compensation of blood flow through the collateral
      circulation during arterial obstructive diseases can act not only in a timely
      fashion but also much more efficiently compared to angiogenesis, the sprouting of
      new capillaries, and a mechanism occurring in a delayed fashion while increases
      the total resistance of the vascular bed of the affected territory.
      Interestingly, despite the vast differences between the two vascular remodeling
      mechanisms, some crucial growth factors and cytokines involved in angiogenesis
      are also required for arteriogenesis. Understanding the mechanisms underlying
      vascular remodeling after ischemic brain injury is a critical step towards the
      development of effective therapies for ischemic stroke. The present article will
      discuss our current views in vascular remodeling acutely after brain ischemia,
      namely arteriogenesis, and some relevant clinical therapies available on the
      horizon in augmenting collateral flow that hold promise in treating ischemic
      brain injury. This article is part of a Special Issue entitled SI: Cell
      Interactions In Stroke. 

PMID- 25770820
TI  - CMA33/XCT Regulates Small RNA Production through Modulating the Transcription of
      Dicer-Like Genes in Arabidopsis.
AB  - Small RNAs (sRNAs) play important regulatory roles in various aspects of plant
      biology. They are processed from double-stranded RNA precursors by Dicer-like
      (DCL) proteins. There are three major classes of sRNAs in Arabidopsis: DCL1
      dependent microRNA (miRNA), DCL3-dependent heterochromatic siRNA (hc-siRNA), and
      DCL4-dependent trans-acting siRNA (ta-siRNA). We have previously isolated a
      mutant with compromised miRNA activity, cma33. Here we show that CMA33 encodes a
      nuclear localized protein, XAP5 CIRCADIAN TIMEKEEPER (XCT). The cma33/xct
      mutation led to reduced accumulation of not only miRNAs but also hc-siRNAs and ta
      siRNAs. Intriguingly, we found that the expression of DCL1, DCL3, and DCL4, but
      not other genes in the sRNA biogenesis pathways, was decreased in cma33/xct.
      Consistent with this, the occupancy of Pol II at DCL1, DCL3, and DCL4 genes was
      reduced upon the loss of CMA33/XCT. Collectively, our data suggest that CMA33/XCT
      modulates sRNA production through regulating the transcription of DCLs. 

PMID- 25770818
TI  - What goes up, can come down: Novel brain stimulation paradigms may attenuate
      craving and craving-related neural circuitry in substance dependent individuals.
AB  - Vulnerability to drug related cues is one of the leading causes for continued use
      and relapse among substance dependent individuals. Using drugs in the face of
      cues may be associated with dysfunction in at least two frontal-striatal neural
      circuits: (1) elevated activity in medial and ventral areas that govern limbic
      arousal (including the medial prefrontal cortex (MPFC) and ventral striatum) or
      (2) depressed activity in dorsal and lateral areas that govern cognitive control
      (including the dorsolateral prefrontal cortex (DLPFC) and dorsal striatum).
      Transcranial magnetic stimulation (TMS) is emerging as a promising new tool for
      the attenuation of craving among multiple substance dependent populations. To
      date however, nearly all repetitive TMS studies in addiction have focused on
      amplifying activity in frontal-striatal circuits that govern cognitive control.
      This manuscript reviews recent work using TMS as a tool to decrease craving for
      multiple substances and provides a theoretical model for how clinical researchers
      might approach target and frequency selection for TMS of addiction. To buttress
      this model, preliminary data from a single-blind, sham-controlled, crossover
      study of 11 cocaine-dependent individuals is also presented. These results
      suggest that attenuating MPFC activity through theta burst stimulation decreases
      activity in the striatum and anterior insula. It is also more likely to attenuate
      craving than sham TMS. Hence, while many TMS studies are focused on applying LTP
      like stimulation to the DLPFC, the MPFC might be a new, efficacious, and
      treatable target for craving in cocaine dependent individuals.

PMID- 25770821
TI  - Aedes aegypti salivary gland extract ameliorates experimental inflammatory bowel
      disease.
AB  - Current therapies for inflammatory bowel disease (IBD) are not totally effective,
      resulting in persistent and recurrent disease for many patients. Mosquito saliva
      contains immunomodulatory molecules and therein could represent a novel therapy
      for IBD. Here, we demonstrated the therapeutic activity of salivary gland extract
      (SGE) of Aedes aegypti on dextran sulfate sodium (DSS)-induced colitis. For this
      purpose, C57BL/6 male mice were exposed to 3% DSS in drinking water and treated
      with SGE at early (days 3-5) or late (days 5-8) time points, followed by
      euthanasia on days 6 and 9, respectively, for sample collection. The results
      showed an improvement in clinical disease outcome and postmortem scores after SGE
      treatment, accompanied by the systemic reduction in peripheral blood lymphocytes,
      with no impact on bone marrow and mesenteric lymph nodes cellularity or
      macrophages toxicity. Moreover, a local diminishment of IFN-gamma, TNF-alpha, IL
      1beta and IL-5 cytokines together with a reduction in the inflammatory area were
      observed in the colon of SGE-treated mice. Strikingly, early treatment with SGE
      led to mice protection from a late DSS re-challenging, as observed by decreased
      clinical and postmortem scores, besides reduced circulating lymphocytes,
      indicating that the mosquito saliva may present components able to prevent
      disease relapse. Indeed, high performance liquid chromatography (HPLC)
      experiments pointed to a major SGE pool fraction (F3) able to ameliorate disease
      signs. In conclusion, SGE and its components might represent a source of
      important immunomodulatory molecules with promising therapeutic activity for IBD.

PMID- 25770819
TI  - Low-dose TNF augments fracture healing in normal and osteoporotic bone by up
      regulating the innate immune response.
AB  - The mechanism by which trauma initiates healing remains unclear. Precise
      understanding of these events may define interventions for accelerating healing
      that could be translated to the clinical arena. We previously reported that
      addition of low-dose recombinant human TNF (rhTNF) at the fracture site augmented
      fracture repair in a murine tibial fracture model. Here, we show that local rhTNF
      treatment is only effective when administered within 24 h of injury, when
      neutrophils are the major inflammatory cell infiltrate. Systemic administration
      of anti-TNF impaired fracture healing. Addition of rhTNF enhanced neutrophil
      recruitment and promoted recruitment of monocytes through CCL2 production.
      Conversely, depletion of neutrophils or inhibition of the chemokine receptor CCR2
      resulted in significantly impaired fracture healing. Fragility, or osteoporotic,
      fractures represent a major medical problem as they are associated with permanent
      disability and premature death. Using a murine model of fragility fractures, we
      found that local rhTNF treatment improved fracture healing during the early phase
      of repair. If translated clinically, this promotion of fracture healing would
      reduce the morbidity and mortality associated with delayed patient mobilization.

PMID- 25770822
TI  - Simple preparation of lotus-root shaped meso-/macroporous TiO2 and their DSSC
      performances.
AB  - In pursuit of superior TiO2 photoanode materials for dye-sensitized solar cells
      (DSSCs), we prepared lotus-root shaped meso-/macroporous TiO2. The lotus-root
      shaped meso-/macroporous TiO2 was easily prepared by using a
      cetyltrimethylammonium hydroxide (CTAOH) template in aqueous solution. The
      crystallization of the as-prepared amorphous lotus-root shaped TiO2 was performed
      at 700  degrees C in air. Crystalline anatase phase with a very small portion of
      rutile phase was generated after the heat treatment at 700  degrees C and the BET
      surface area of crystalline lotus-root shaped meso-/macroporous TiO2 material (LR
      700) was 30.0 m(2) g(-1). The wall of LR-700 displayed well-developed
      mesoporosity with a pore dimension of 28.3 nm. Periodically arranged microscale
      one-dimensional (1D) macropores were also observed in the particles. The photon
      to-current conversion efficiencies (eta) of LR-700 photoanodes in Gratzel type
      DSSCs were examined. The conversion efficiency of DSSC prepared by mixing
      nanoparticulate Evonik P25 and LR-700 (ratio=85:150 by mass) was 28% greater
      compared to the reference electrode using P25. Incident photon-to-current
      efficiencies (IPCE) of the DSSCs were dramatically improved by employing the
      photoanodes composed of a mixture of P25 and LR-700 but impedance analysis
      indicated that P25/LR-700 mixed cells have resistances similar to the standard
      P25 reference cell. Thus, photovoltaic performances could be improved mainly due
      to the increases of dye uptake and external quantum efficiency by using a mixed
      photoanode composed of LR-700 and nanocrystalline P25 particles.

PMID- 25770823
TI  - Structural, compositional and textural properties of monoclinic alpha-Bi2O3
      nanocrystals.
AB  - Perfect alpha-Bi2O3 nanocrystals were successfully synthesized via green
      synthesis method. X-ray diffraction studies clearly revealed a single phase alpha
      Bi2O3 nanocrystal without any secondary phase. The strong XPS peaks observed at
      160 and 165 eV were assigned to Bi4f5/2 and Bi4f7/2 and clearly revealed Bi(3+)
      valence states of bismuth ions. Photoluminescence spectra revealed the perfect
      alpha-Bi2O3 crystal nature without having inter band transitions between defects,
      impurity and different valence states of bismuth ions. Out of thirty expected
      modes, the symmetry assignments of Raman bands correlated to Bg(4), Ag(5), Bg(5),
      Bg(6), Ag(7), Ag(8), Ag(9), Ag(10), Ag(12) and Ag(14) modes revealed perfect
      alpha-Bi2O3 nanocrystals. Transmission electron microscopy studies combined with
      a selected area electron diffraction pattern recorded on alpha-Bi2O3 nanocrystals
      show monoclinic structure preferential orientation with sizes approximately 200
      nm in diameters and 500 nm in length.

PMID- 25770824
TI  - Neurobehavioral and neurophysiological effects after acute exposure to a single
      peak of 200 ppm toluene in healthy volunteers.
AB  - The solvent toluene has neurotoxic properties that are especially relevant in the
      working environment. Short-term exposure limits (STELs) vary from 50 ppm up to
      300 ppm across countries but their acute effects remain elusive in humans.
      Several in vitro and in vivo studies elucidated that toluene acutely acts by
      perturbations of different neurotransmitter systems. More specifically visual
      evoked potentials (VEPs) of rats are decreased after acute toluene exposure,
      leading to the assumption that particularly visual attention processes might be a
      target of toluene in humans. Therefore a visual change detection task was applied
      to measure both neurobehavioral and neurophysiological effects by using
      electroencephalography (EEG) after a single peak exposure to 200 ppm toluene.
      Performance and event-related components of the EEG were examined before and
      after exposure in a toluene-exposed and a control group. Thirty-three young
      healthy volunteers participated in this study. The behavioral results of the
      experiment indicate that toluene impairs the rate of correct responses especially
      in task conditions in which an irrelevant distractor is given, while the response
      times did not differ between both groups. The neurophysiological findings hint
      toward a less efficient visual processing of behaviorally relevant stimuli and an
      increased distractibility by irrelevant distractors. Thus the present results are
      a promising starting point for further research specifically targeting visual
      attention after toluene exposure and the reconsideration of the presently very
      heterogeneous STELs.

PMID- 25770826
TI  - T-cells enhance stem cell mutagenesis in the mouse colon.
AB  - A role of inflammation in the etiology of cancer is attributed to the production
      of reactive oxygen/nitrogen species that can damage DNA. To test this hypothesis,
      we determined the mutation frequency (MF) in colonic stem cells in C57Bl/6 mice
      exposed to azoxymethane (AOM), dextran sulfate sodium (DSS) and a combination of
      AOM and DSS (AOM+DSS). AOM+DSS efficiently and rapidly produces colon tumors in
      B6 mice. AOM produces promutagenic O(6)-methylguanine lesions in DNA but does not
      induce colon tumors in C57Bl/6 mice as a single agent. DSS produces inflammation
      in the colon but does not produce tumors except upon multiple cycles of treatment
      in some DNA repair deficient mouse models. In addition, using TCRbeta null mice
      we tested whether alpha/beta T cells have any effect on the colonic stem cell MF
      in mice treated with AOM, DSS and AOM+DSS. The TCRbeta(-/-) mice are devoid of
      the critical receptor required for normal cytolytic and regulatory alpha/beta T
      cell functions. The MF in the untreated and DSS treated WT and TCRbeta(-/-) mice
      was the same (<10(-5)) indicating that DSS and subsequent inflammation does not
      generate stem cell mutations in mice that are WT for DNA repair. AOM yielded
      mutant crypts in WT and TCRbeta(-/-) mice with MF's of ~4*10(-4) and 2*10(-4),
      respectively, which represents a statistically significant decrease in the MF in
      the immune compromised mice. The combined treatment of AOM+DSS afforded fully
      mutated crypts in both strains with a statistically significant lower MF in the
      TCRbeta(-/-) mice. In addition, the MF in both strains of mice after the
      combination of AOM+DSS is lower than observed with AOM alone indicating that DSS
      inflammation destroyed pre-existing AOM mutated crypts. Using the MF in WT mice,
      the efficiency for the conversion of promutagenic O(6)-methylguanine lesions into
      a stem cell mutations was calculated to be ~0.4%. 

PMID- 25770825
TI  - Differential expression of circulating microRNAs according to severity of
      colorectal neoplasia.
AB  - There is a need to develop a colorectal cancer (CRC) screening test that is
      noninvasive, cost effective, and sensitive enough to detect preneoplastic
      lesions. This case-control study examined the feasibility of using circulating
      extracellular microRNAs (miRNAs) to differentiate a spectrum of colorectal
      neoplasia of various severity and hence for early detection of colorectal
      neoplasia. Archived serum samples of 10 normal controls and 31 cases, including
      10 with nonadvanced adenoma, 10 with advanced adenoma, and 11 with CRC, were
      profiled for circulating miRNAs using next-generation sequencing. Multiple linear
      regression, adjusting for age, gender, and smoking status, compared controls and
      the 3 case groups for levels of 175 miRNAs that met stringent criteria for miRNA
      sequencing analysis. Of the 175 miRNAs, 106 miRNAs were downregulated according
      to severity of neoplasia and showed a relative decrease in the expression from
      controls to nonadvanced adenoma to advanced adenoma to CRC (Ptrend < 0.05).
      Pairwise group comparisons showed that 39 and 80 miRNAs were differentially
      expressed in the advanced adenoma and CRC groups compared with the controls,
      respectively. Differences in miRNA levels between the nonadvanced adenoma group
      and controls were modest. Our study found that expression of many miRNAs in serum
      was inversely correlated with the severity of colorectal neoplasia, and
      differential miRNA profiles were apparent in preneoplastic cases with advanced
      lesions, suggesting circulating miRNAs could serve as potential biomarkers for
      CRC screening. 

PMID- 25770827
TI  - MYC impairs resolution of site-specific DNA double-strand breaks repair.
AB  - Although it is established that when overexpressed, the MYC family proteins can
      cause DNA double-stand breaks (DSBs) and genome instability, the mechanisms
      involved remain unclear. MYC induced genetic instability may result from
      increased DNA damage and/or reduced DNA repair. Here we show that when
      overexpressed, MYC proteins induce a sustained DNA damage response (DDR) and
      reduce the wave of DSBs repair. We used a cell-based DSBs system whereby, upon
      induction of an inducible restriction enzyme AsiSI, hundreds of site-specific
      DSBs are generated across the genome to investigate the role of MYC proteins on
      DSB. We found that high levels of MYC do not block accumulation of gammaH2AX at
      AsiSI sites, but delay its clearance, indicating an inefficient repair, while the
      initial recognition of DNA damage is largely unaffected. Repair of both
      homologous and nonhomologous repair-prone segments, characterized by high or low
      levels of recruited RAD51, respectively, was delayed. Collectively, these data
      indicate that high levels of MYC proteins delay the resolution of DNA lesions
      engineered to occur in cell cultures. 

PMID- 25770828
TI  - Discovery of novel anti-parkinsonian effect of schisantherin A in in vitro and in
      vivo.
AB  - Dibenzocyclooctadiene lignans represent a unique group of natural chemical
      structures, are considered as protectants against neuronal cell death and
      cognitive impairment in neurological disorders. Among the family of
      dibenzocyclooctadiene lignan analogs from the fruit of Schisandra chinensis
      (Turcz.) Baill, neuroprotective potential of schisantherin A (StA) has not yet
      been characterized. In this study, 1-methyl-4-phenylpyridinium ion (MPP(+))
      incubated SH-SY5Y cells and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)
      treated mice were used to study the neuroprotection of StA. Pretreatment with StA
      significantly inhibited MPP(+)-induced cytotoxicity in SH-SY5Y cells. Moreover,
      StA conferred significant protection against MPTP-induced loss of TH-positive
      dopaminergic neurons in a Parkinson's disease (PD) mice model. Structure activity
      relationship analysis suggested that methylenedioxy, benzoyloxy and methoxyl
      groups, in the dibenzocyclooctadiene lignan of StA, were probably functionally
      important to its neuroprotective activity. In addition, Western blotting analysis
      demonstrated that StA exhibited neuroprotection against MPP(+) through the
      regulation of two distinct pathways including increasing CREB-mediated Bcl-2
      expression and activating PI3K/Akt survival signaling suggesting that StA might
      be a promising neuroprotective agent for the prevention of PD. 

PMID- 25770829
TI  - A combination of keratan sulfate digestion and rehabilitation promotes anatomical
      plasticity after rat spinal cord injury.
AB  - Functional recovery after neuronal injuries relies on neuronal network
      reconstruction which involves many repair processes, such as sealing of injured
      axon ends, axon regeneration/sprouting, and construction and refinement of
      synaptic connections. Chondroitin sulfate (CS) is a major inhibitor of axon
      regeneration/sprouting. It has been reported that the combination of task
      specific rehabilitation and CS-digestion is much more effective than either
      treatment alone with regard to the promotion of functional and anatomical
      plasticity for dexterity in acute and chronic spinal cord injury models. We
      previously reported that keratan sulfate (KS) is another inhibitor and has a
      potency equal to CS. Here, we compared the effects of KS- or CS-digestion plus
      rehabilitation on recovery from spinal cord injury. Keratanase II or
      chondroitinase ABC was locally administered at the lesion after spinal cord
      injury at C3/4. Task-specific rehabilitation training, i.e., a single pellet
      reaching task using a Whishaw apparatus, was done for 3 weeks before injury, and
      then again at 1-6 weeks after injury. The combination of KS-digestion and
      rehabilitation yielded a better rate of pellet removal than either KS-digestion
      alone or rehabilitation alone, although these differences were not statistically
      significant. The combination of CS-digestion and rehabilitation showed similar
      results. Strikingly, both KS-digestion/rehabilitation and CS
      digestion/rehabilitation showed significant increases in neurite growth in vivo
      as estimated by 5-hydroxytryptamine and GAP43 staining. Thus, KS-digestion and
      rehabilitation exerted a synergistic effect on anatomical plasticity, and this
      effect was comparable with that of CS-digestion/rehabilitation. KS-digestion
      might widen the therapeutic window of spinal cord injury if combined with
      rehabilitation. 

PMID- 25770830
TI  - Dementia alters standing postural adaptation during a visual search task in older
      adult men.
AB  - This study investigated the effects of dementia on standing postural adaptation
      during performance of a visual search task. We recruited 16 older adults with
      dementia and 15 without dementia. Postural sway was assessed by recording medial
      lateral (ML) and anterior-posterior (AP) center-of-pressure when standing with
      and without a visual search task; i.e., counting target letter frequency within a
      block of displayed randomized letters. ML sway variability was significantly
      higher in those with dementia during visual search as compared to those without
      dementia and compared to both groups during the control condition. AP sway
      variability was significantly greater in those with dementia as compared to those
      without dementia, irrespective of task condition. In the ML direction, the
      absolute and percent change in sway variability between the control condition and
      visual search (i.e., postural adaptation) was greater in those with dementia as
      compared to those without. In contrast, postural adaptation to visual search was
      similar between groups in the AP direction. As compared to those without
      dementia, those with dementia identified fewer letters on the visual task. In the
      non-dementia group only, greater increases in postural adaptation in both the ML
      and AP direction, correlated with lower performance on the visual task. The
      observed relationship between postural adaptation during the visual search task
      and visual search task performance--in the non-dementia group only--suggests a
      critical link between perception and action. Dementia reduces the capacity to
      perform a visual-based task while standing and thus, appears to disrupt this
      perception-action synergy.

PMID- 25770831
TI  - Connexin 43 mediates PFOS-induced apoptosis in astrocytes.
AB  - Perfluorooctane sulfonate (PFOS) is a man-made environmental pollutant that is
      toxic to mammals. However, the neurotoxic effects of PFOS remain largely
      unexplored. In this study, we determined the role of an astrocyte specific gap
      junction protein, connexin 43 (Cx43), in PFOS-induced apoptosis. The rate of
      astrocyte apoptosis was higher in cortex astrocytes after PFOS treatment. These
      astrocytes also showed up-regulated expression of Cx43 and higher levels of
      cleaved caspase-3. Elevated ROS accumulation and decreased DeltaPsim also
      confirmed the presence of PFOS-induced apoptosis. However, the exposure of
      astrocytes to PFOS together with carbenoxolone (CBX) significantly reduced both
      Cx43 and cleaved caspase-3 levels. These results indicate that Cx43 plays a
      proapoptotic role in PFOS-induced apoptosis in cortex astrocyte cells. 

PMID- 25770832
TI  - Bioconcentration of phenanthrene and metabolites in bile and behavioral
      alterations in the tropical estuarine guppy Poecilia vivipara.
AB  - Quantification of polycyclic aromatic hydrocarbon (PAH) metabolites in fish bile
      is widely used to evaluate levels of internal PAH contamination in fish, whereas
      behavioral effects are deemed important to address potential risks to fish
      populations. The estuarine guppy Poecilia vivipara was exposed for 96h to
      waterborne phenanthrene at concentrations of 10, 50, 200 and 500MUgL(-1).
      Phenanthrene and metabolites in bile were analyzed by fixed fluorescence at
      260/380nm (excitation/emission) wavelengths. Phenanthrene increased in the bile
      of exposed fish in a dose-dependent pattern, and log bile bioconcentration
      factors ranged from 4.3 to 3.9 at 10 and 500MUgL(-1) phenanthrene, respectively,
      values that are similar to predicted bioconcentration factors based on
      phenanthrene Kow. Swimming resistance index was reduced to 81% of control values
      at 500MUgL(-1). Alteration of swimming speed was non monotonic, with a
      significant speed increase relative to control fish in treatments 50 and 200MUgL(
      1) phenanthrene, respectively, followed by a speed decrease in fish exposed to
      500MUgL(-1). However, swimming trajectories of fish exposed to 50, 200 and
      500MUgL(-1) was altered by the development of a repetitive circular swimming
      behavior, in contrast to the controls that explored the entire experimental
      arena. This change in swimming patterns apparently explains the reduction in prey
      capture rates at 200MUgL(-1) phenanthrene. This study provides important
      information enabling the use of the estuarine guppy P. vivipara to monitor PAH
      metabolites in bile and its bioconcentration, linking internal exposure with
      ecologically relevant behavioral effects in the species. 

PMID- 25770833
TI  - Diastereoisomer-specific effects of hexabromocyclododecanes on hepatic aryl
      hydrocarbon receptors and cytochrome P450s in zebrafish (Danio rerio).
AB  - In order to elucidate the mechanism for diastereoisomer-specific toxicity and
      metabolism of hexabromocyclododecanes (HBCDs) in biota, zebrafish (Danio rerio)
      were exposed to different concentrations of individual HBCD diastereoisomers
      (alpha-, beta- and gamma-HBCD) in water for 7 and 21d. We examined the gene
      expression of aryl hydrocarbon receptor (AHR) and cytochrome P450 (CYP), as well
      as ethoxyresorufin-O-deethylase (EROD) activity in zebrafish livers. Exposure to
      different HBCD diastereoisomers caused different expression of AHRs in zebrafish
      livers. For instance, 10 and 100MUgL(-1) of alpha- and beta-HBCD up-regulated the
      expressions of ahr1a and ahr1b in zebrafish liver, whereas 10 and 100MUgL(-)(1)
      of gamma-HBCD down-regulated them after 7d exposure. alpha-HBCD showed the most
      significant up-regulation of ahr1a and ahr1b expression, whereas gamma-HBCD
      showed the most significant down-regulation of their expression among three HBCD
      diastereoisomers. Moreover, HBCDs could affect the expression of CYP1s as well as
      EROD activity in a gene-specific and diastereoisomer-specific manner. alpha-,
      beta- and gamma-HBCD inhibited cyp1a expression but enhanced the expression of
      cyp1b1 and cyp1c1. alpha-, beta- and gamma-HBCD showed different degrees of
      effect on the same CYP1 gene in a concentration-dependent way. The different
      effects of HBCD diastereoisomers on these genes we examined and EROD activity not
      only indicate diastereoisomer-specific toxic effect, but also in turn explain
      diastereoisomer-specific accumulation of HBCDs in zebrafish. 

PMID- 25770834
TI  - Inhibitory effects and oxidative target site of dibutyl phthalate on Karenia
      brevis.
AB  - The inhibitory action and possible damage mechanism of dibutyl phthalate (DBP) on
      the red tide algae Karenia brevis were investigated. The results showed that the
      algae experienced oxidative stress after exposure to 5mgL(-1) DBP.
      Malondialdehyde (MDA) peaked after 72h, with a value approximately 2.3 times
      higher than that observed for untreated cells. The superoxide dismutase (SOD) and
      catalase (CAT) activities significantly increased as an adaptive reaction after
      48h. DBP induced the overproduction of reactive oxygen species (ROS), the OH
      concentration showed a peak of 33UmL(-1) at 48h, and the highest H2O2 content was
      approximately 250nmol/10(7) cells at 72h; these latter two values were 2.5 and
      4.4 times higher than observed for the control, respectively. TEM images showed
      that a number of small vacuoles or apical tubers were commonly found around the
      cell membrane, and the membrane structure was ultimately disintegrated. Further
      experiments were carried out to locate the original ROS production sites
      following DBP exposure. The activity of CuZn-SOD (a mainly cytosolic isoform,
      with some also found in chloroplasts) under DBP exposure was approximately 2.5
      times higher than the control, whereas the Mn-SOD (mitochondrial isoform)
      activity was significantly inhibited. No significant difference was observed in
      the activity of Fe-SOD (chloroplastic isoform). In addition, dicumarol (an
      inhibitor of the electron transport chain in the plasma membrane) stimulated DBP
      induced ROS production, whereas rotenone (an inhibitor of the mitochondria
      electron transport chain complex I) decreased DBP-induced ROS production. These
      results suggested that mitochondria could be the main target sites for DBP
      attack. 

PMID- 25770835
TI  - Chronic exposure to cigarette smoke causes extrapulmonary abnormalities in rats.
AB  - Pathophysiological features of chronic obstructive pulmonary disease (COPD)
      include systemic abnormalities, such as weight loss and skeletal muscle wasting.
      Although cigarette smoke (CS) is a major risk factor in COPD, the systemic
      effects of CS exposure remain to be elucidated. In this study, rats were exposed
      to CS or smoke-free air for 12 weeks. CS-exposed rats developed emphysema and had
      significantly lower body weight and food intake than control rats. The plasma
      ghrelin levels significantly increased with an upregulation of gastric ghrelin
      mRNA expression induced by CS exposure. Further, we observed low plasma insulin
      like growth factor-1 levels and high tumor necrosis factor-alpha levels. A
      significant reduction of skeletal muscle strength and an increase in the mRNA
      expression of catabolic factors was observed in CS-exposed rats. These results
      indicated that chronic CS exposure induced not only pulmonary emphysema but also
      systemic abnormalities related to muscle catabolism associated with inflammatory
      responses. 

PMID- 25770836
TI  - Anatomic-histologic study of the floor of the mouth: the lingual lymph nodes.
AB  - OBJECTIVE: The lingual lymph nodes are inconstant nodes located within the
      fascial/intermuscular spaces of the floor of the mouth. Oral tongue squamous cell
      carcinoma has been reported to recur and metastasize in lingual lymph nodes with
      poor prognosis. Lingual lymph nodes are not currently included in basic tongue
      squamous cell carcinoma surgery. METHODS: Twenty-one cadavers (7 males, 14
      females) were studied, aged from 57 to 94 years (mean age 76.3 years). The gross
      specimen of the floor of the mouth was divided into blocks: A (median nodes), B,
      B' (parahyoid), C, C' (paraglandular). Serial histological microslides were cut
      and stained with hematoxylin-eosin. Frequency of lingual lymph nodes in each
      block and their microscopic features were assessed. RESULTS: The lingual lymph
      nodes in overall number of 7 were detected in 5 of the 21 cadavers (23.8%). The
      total incidence of lingual lymph node was 33.3% (7 nodes/21 cadavers). Block A
      failed to demonstrate any lymph nodes (0%); Blocks B, B'-2 nodes (9.5%) and 2
      nodes (9.5%), respectively; Blocks C, C'-1 node (4.8%) and 2 nodes (9.5%),
      respectively. The mean lingual lymph node length was 4.1 mm (from 1.4 to 8.7 mm),
      the mean thickness was 2.8 mm (from 0.8 to 7.5 mm). Five cadavers (23.8%)
      revealed mucosa-associated lymphoid tissue. Atrophic changes appeared in 4
      (57.1%) lingual lymph nodes. CONCLUSION: The presence of lymph node-bearing
      tissue in the floor of the mouth is demonstrated. In account of resection
      radicalism and better local control the fat tissue of the floor of the mouth
      should be removed in conjunction to glossectomy. Further anatomic and clinical
      research is required to establish the role of lingual lymph node in oral squamous
      cell carcinoma recurrence and metastasis.

PMID- 25770837
TI  - Impact of modifiable lifestyle factors on outcomes after breast cancer diagnosis:
      the Setouchi Breast Cancer Cohort Study.
AB  - The primary purpose of this large cohort study is to investigate the effects on
      breast cancer outcomes of modifiable lifestyle factors after breast cancer
      diagnosis. These factors include physical activity, smoking, alcohol consumption,
      obesity and weight gain after diagnosis, alternative medicine and dietary
      factors. Women diagnosed with Stage 0 to III breast cancer are eligible for
      participation to this study. Lifestyle, use of alternative medicine, psychosocial
      factors, reproductive factors and health-related quality of life will be assessed
      using a questionnaire at the time of breast cancer diagnosis (baseline), and 1,
      2, 3 and 5 years after diagnosis. Clinical information and breast cancer outcomes
      will be obtained from a breast cancer database. The primary endpoint will be
      disease-free survival. Secondary endpoints are overall survival, health-related
      quality of life, breast cancer-related symptoms and adverse events. Patient
      recruitment commenced in February 2013. Enrollment of 2000 breast cancer patients
      is planned during the 5-year recruitment period. The concept of the study is
      described in this article. 

PMID- 25770838
TI  - Brachial-ankle pulse wave velocity and blood pressure control in treated
      hypertensive patients.

PMID- 25770839
TI  - "Neurogenic stress cardiomyopathy in heart donors" is a form of Takotsubo
      syndrome.

PMID- 25770840
TI  - Fetal cardiac Doppler indices in fetuses with hemoglobin Bart's disease at 12
      14weeks of gestation.

PMID- 25770841
TI  - Diabetes mellitus and atrial fibrillation: Pathophysiological mechanisms and
      potential upstream therapies.
AB  - Diabetes mellitus (DM) represents one of the most important risk factors for
      atrial fibrillation (AF) while AF is a strong and independent marker of overall
      mortality and cardiovascular morbidity in diabetic patients. Autonomic,
      electrical, electromechanical, and structural remodeling, including oxidative
      stress, connexin remodeling and glycemic fluctuations seem to be implicated in AF
      pathophysiology in the setting of DM. The present review highlights the
      association between DM and AF, provides a comprehensive overview of the
      responsible pathophysiological mechanisms and briefly discusses potential
      upstream therapies for DM-related atrial remodeling. 

PMID- 25770842
TI  - Is cervical length associated with maternal characteristics?
AB  - OBJECTIVE: Women with a mid-trimester short cervical length (CL) are at increased
      risk for preterm delivery. Consequently, CL measurement is a potential screening
      tool to identify women at risk for preterm birth. Our objective was to assess
      possible associations between CL and maternal characteristics. STUDY DESIGN: A
      nationwide screening study was performed in which CL was measured during the
      standard anomaly scan among low risk women with a singleton pregnancy. Data on
      maternal height, pre-pregnancy weight, ethnicity, parity and gestational age at
      the time of the CL measurement were collected from January 2010 to December 2012.
      Univariable and multivariable linear regression analyses were performed to assess
      the relationship between CL and maternal characteristics. RESULTS: We included
      5092 women. The mean CL was 44.3mm. No association was found between CL and
      maternal height or gestational age of the measurement. Maternal weight was
      associated with CL (p=0.007, adjusted R(2) 0.03). Separate analysis for BMI did
      not change these results. Ethnicity, known in 2702 out of 5092 women, was
      associated with CL (mean CL in Caucasian women 45.0mm, Asian 43.9mm,
      Mediterranean 43.1mm, and African 41.8mm, p=0.003), as well as parity (mean CL
      multiparous 45.3mm, nulliparous 43.5mm, p<0.0001). CONCLUSION: Shorter mid
      trimester cervical length is associated with higher maternal weight, younger
      maternal age, nulliparity and non-Caucasian ethnicity, but not with maternal
      height.

PMID- 25770843
TI  - Conventional semen parameters and DNA fragmentation in relation to fertility
      status in a Greek population.
AB  - OBJECTIVES: Our study aimed to investigate the possible correlations between
      conventional seminal parameters and DNA fragmentation in specific groups of Greek
      men, selected in relation to their fertility history and to verify the validity
      of the recent WHO reference values for the basic semen analysis in this
      population. STUDY DESIGN: A total of 770 subject data were evaluated in three
      distinct groups: fertile men with children naturally conceived within one year of
      unprotected intercourse (n=78), subfertile men, having achieved pregnancies
      either naturally or by Assisted Reproduction Techniques, not resulting in live
      births (n=153) and infertile men, failing to produce either pregnancies or
      children (n=539). Semen volume, sperm concentration, total count, rapid and total
      progressive motility and morphology were evaluated following the World Health
      Organization (2010) methods. DNA fragmentation was assessed by the Sperm
      Chromatin Dispersion assay. The 5th percentile, as well as the 95% confidence
      intervals (CI) for each parameter, were calculated by the method of
      bootstrapping. Statistical correlations between the examined parameters were
      sought using the Spearman R test (p<0.05). RESULTS: A significant inverse
      correlation was established between DNA fragmentation and sperm concentration,
      total count, progressive motility (rapid and total) and normal morphology in
      subfertile and infertile men (p<0.05). No statistically significant correlations
      were remarked between the conventional semen parameters and the levels of DNA
      fragmentation in our group of fertile men. Concordance was established between
      the reference limits issued by the WHO 2010 for the basic semen parameters and
      semen quality of fertile men in the studied population. CONCLUSIONS: The
      variability of correlations established between DNA fragmentation and the
      conventional seminal profile in relation to fertility status indicates that they
      are independent attributes of semen quality, justifying the assessment of both
      during a comprehensive evaluation of male infertility. Moreover, the WHO 2010
      reference limits were found adequately descriptive of seminal normality in Greek
      men.

PMID- 25770845
TI  - Term histologic chorioamnionitis: a heterogeneous condition.
AB  - A histologic response of histologic chorioamnionitis (HCA) is defined as an
      intrauterine inflammatory condition characterized by acute granulocyte
      infiltration into the fetal-maternal or the fetal tissues. Prevalence of HCA is
      inversely correlated with gestational age, occurring in 50% of preterm birth and
      in up to 20% of deliveries at term. Regardless of these standard definitions,
      understanding HCA is challenging as it reflects a heterogeneous condition. A
      histologic response of HCA from term placentas often does not correspond to a
      clinical presentation; in this context, the present review aims to analyze main
      characteristics of this condition, in particular focusing on mechanisms and birth
      outcomes.

PMID- 25770844
TI  - The risk of preterm birth of treated versus untreated cervical intraepithelial
      neoplasia (CIN): a systematic review and meta-analysis.
AB  - Cervical surgery is associated with preterm birth (PTB) and neonatal morbidity.
      However, it is unknown whether this increased risk is due to the surgery itself
      or to the cervical intraepithelial neoplasia (CIN) underlying the surgery. Our
      objective was to assess the risk for PTB in women with treated and untreated CIN.
      We performed an electronic literature search in MEDLINE, Embase and CENTRAL for
      studies that reported on pregnancy outcome after treated and untreated CIN. The
      methodological quality was scored using the STROBE combined checklist for
      observational studies. We extracted data on PTB<37 weeks, very PTB<32 weeks,
      spontaneous PTB<37 weeks, (preterm) premature rupture of membranes ((P)PROM),
      perinatal mortality and section caesarean each before and after treatment for
      CIN. We used the Mantel-Haenszel method to estimate summarizing odds ratios. Our
      search identified 620 studies, of which 20 were reporting on pregnancy outcome
      for a total of 12,159,293 women. There were 20,832 women who gave birth after
      treatment for CIN before pregnancy, 52 women who gave birth after treatment for
      CIN during pregnancy, 64,237 women with CIN who gave birth before treatment, and
      8,902,865 women who gave birth without CIN. Compared to women with untreated CIN,
      women treated for CIN before or during pregnancy, had a significantly higher risk
      of PTB<37 weeks (OR 1.7, 95% CI 1.0-2.7). When comparing women treated for CIN
      before pregnancy (n=20,832) to women with untreated CIN (n=64,162), we found an
      OR of 1.4 with a 95% confidence interval of 0.85-2.3. Women treated during
      pregnancy had a clearly increased risk for PTB (OR 6.5, 95% CI 1.1-37), and
      (P)PROM (OR 1.8, 95% CI 1.4-2.2). In women with cervical surgery, the risks for
      spontaneous PTB<37 weeks (OR 0.87, 95% CI 0.54-1.4), caesarean section (OR 1.0,
      95% CI 0.71-1.5) and perinatal mortality (OR 1.0, 95% CI 0.38-2.8) were not
      increased. The increased risk of PTB in women who underwent cervical surgery for
      CIN is especially increased when performed during pregnancy. When performed
      before pregnancy the risk of PTB is increased, although insignificant. 

PMID- 25770846
TI  - Reproducibility of three-dimensional ultrasound for the measurement of a niche in
      a caesarean scar and assessment of its shape.
AB  - OBJECTIVE: To evaluate the inter- and intraobserver agreement for measurement of
      the size and volume of a niche and assessment of the shape, with the use of three
      dimensional (3D) ultrasound. STUDY DESIGN: In this reproducibility study, 20 3D
      ultrasound volumes of uteri with a niche were selected, based on complete
      visualisation of the uterus and niche in both the longitudinal and transversal
      plane. Niche measurements were performed off-line twice by one observer and once
      by another observer. Niche measurements and assessment of shape were performed in
      the longitudinal and transversal plane, and niche volume in the longitudinal
      plane. The mean difference, 95% limits of agreement, the intraclass correlation
      coefficient (ICC) and Cohen's kappa were calculated to assess the inter- and
      intraobserver agreement. RESULTS: The interobserver agreement was excellent for
      all niche measurements (ICC >0.86), including depth and residual myometrial
      thickness (RMT), except for width at niche base in the transversal plane (ICC
      0.74) and niche volume (ICC 0.79), which were classified as good agreement. Wide
      limits of agreement and a high mean difference were found for maximal width in
      the transversal plane. The intraobserver agreement was excellent for all
      measurements (ICC >0.80), except for RMT in the longitudinal and transversal
      plane, which were classified as good agreement (ICC 0.73 and 0.62, respectively).
      Wide limits of agreement were found for maximal width and width at niche base in
      the transversal plane. The overall agreement in the transversal plane was lower
      than in the longitudinal plane, but still all in the range of good agreement. The
      inter- and intraobserver agreement was good to poor for the assessment of niche
      shape. CONCLUSION: Using 3D ultrasound, various niche parameters, including depth
      (both perpendicular to niche base and maximal depth), maximal width, width at
      niche base, RMT and volume, can be measured with a high level of agreement, in
      particular if measured in the longitudinal plane.

PMID- 25770847
TI  - Nickel transfer by fingers.
AB  - We investigated fingers as a potential source of nickel transfer to the face in
      patients with allergic contact dermatitis to nickel and a history of facial
      dermatitis. Samples were collected from the fingers and cheeks of volunteers
      using the stripping method with standard adhesive tape, and nickel levels were
      quantified using mass spectrometry. Fingers and cheeks of individuals who had
      handled coins were both positive for nickel, with levels ranging from 14.67 to
      58.64 ppm and 1.28 to 8.52 ppm, respectively. The levels in a control group were
      considerably and significantly lower. Transfer of nickel from a person's fingers
      to their face after handling a nickel-containing object could explain the
      presence of facial dermatitis in patients with nickel hypersensitivity. 

PMID- 25770848
TI  - Fast-Growing Pigmented Nodular Lesions.

PMID- 25770849
TI  - Radionuclide myocardial perfusion imaging for the evaluation of patients with
      known or suspected coronary artery disease in the era of multimodality
      cardiovascular imaging.
AB  - Over the last several decades, radionuclide myocardial perfusion imaging (MPI)
      with single photon emission tomography and positron emission tomography has been
      a mainstay for the evaluation of patients with known or suspected coronary artery
      disease (CAD). More recently, technical advances in separate and complementary
      imaging modalities including coronary computed tomography angiography, computed
      tomography perfusion, cardiac magnetic resonance imaging, and contrast stress
      echocardiography have expanded the toolbox of diagnostic testing for cardiac
      patients. While the growth of available technologies has heralded an exciting era
      of multimodality cardiovascular imaging, coordinated and dispassionate
      utilization of these techniques is needed to implement the right test for the
      right patient at the right time, a promise of "precision medicine." In this
      article, we review the maturing role of MPI in the current era of multimodality
      cardiovascular imaging, particularly in the context of recent advances in
      myocardial blood flow quantitation, and as applied to the evaluation of patients
      with known or suspected CAD. 

PMID- 25770850
TI  - CT Assessment of Myocardial Perfusion and Fractional Flow Reserve.
AB  - Coronary computed tomography angiography (CTA) offers a non-invasive method to
      detect coronary plaque and stenosis. However, to date, CTA has been most useful
      as a method of ruling out coronary artery disease (CAD) among patients with low
      to intermediate pretest probability of significant CAD. The reduced specificity
      of CTA for detecting physiologically significant stenosis is a known limitation
      of this technique, particularly since some patients require additional functional
      testing following CTA. Therefore, intense interest has focused on the development
      of methods to determine the functional significance of anatomical lesions
      identified by CTA. This article will discuss two emerging methods: stress
      myocardial perfusion imaging using CT, or CT perfusion, and computer simulation
      of fractional flow reserve. 

PMID- 25770851
TI  - Immuno-histochemical study of ovine cystic echinococcosis (Echinococcus
      granulosus) shows predominant T cell infiltration in established cysts.
AB  - Ovine hydatidosis (OH; Echinococcus granulosus) is endemic in several European
      countries surrounding the Mediterranean basin. There have been a limited number
      of studies aimed at evaluating the local immune response to established tissue
      cysts in the ovine host. In the present study, immunohistochemical analysis of
      lymphocyte populations surrounding established cysts showed a predominance of
      CD3+ T cells compared to CD79+ B cells. A percentage of infiltrating lymphocytes
      were also FoxP3+, suggesting that established ovine cysts may be protected from
      immune aggression through the suppressive action of T regulatory cells. The
      present study contributes to the understanding of local immune responses to ovine
      echinococcosis. 

PMID- 25770852
TI  - Haemonchus contortus resistance to monepantel in sheep.
AB  - In a sheep farm in the Netherlands with a suspected Haemonchus contortus
      resistance to monepantel (Zolvix(r), Novartis Animal Health), a fecal egg count
      reduction test was carried out in two groups of lambs, according to the method of
      the World Association for the Advancement of Veterinary Parasitology. Group 1 was
      the untreated control group, and group 2 was treated with monepantel at the
      manufacturer's recommended dose rate. Efficacy of treatment with monepantel was
      0%. Larval identification of pre- and post-treatment coprocultures revealed 100%
      H. contortus larvae. On this farm, after a perceived reduction in efficacy of
      ivermectin and doramectin, the sheep farmer started using monepantel in July
      2012, and since then, monepantel was used as the sole anthelmintic. Breeding
      sheep were treated twice each year in 2013 and 2014, and lambs two times in 2012,
      four times in 2013, and three times in 2014, before monepantel resistance was
      suspected, and confirmed three weeks later. Although the frequency of monepantel
      treatments on this farm was relatively high with treatments on thirteen separate
      occasions in two years time, possibly establishing favorable conditions for a
      competitive advantage for resistant H. contortus, it is remarkable that
      resistance to monepantel was established in such a very short period. This study
      confirms, to the best of our knowledge, the first case of H. contortus resistance
      to monepantel occurring in the field.

PMID- 25770853
TI  - Controlling nematodes in dairy calves using targeted selective treatments.
AB  - With increasing concerns of anthelmintic resistance in cattle nematode
      populations worldwide, there is a need to explore alternative approaches to
      nematode control. One alternative approach is the use of targeted selective
      treatments (TST) where only individual animals are treated instead of the entire
      group. This study reports the findings of a TST approach in dairy calves
      conducted over their first grazing season (FGS) to control both gastrointestinal
      nematode and lungworm challenge. Ninety-six calves with an initial mean (s.d.)
      age and live weight of 130 (28.3) days and 120 (23.6)kg, respectively, were
      randomised by breed, age and live weight to one of two treatments; Control (n=24;
      *2) and TST (n=24; *2). Control calves were treated three times at pasture with
      ivermectin by subcutaneous injection. Individual calves in the TST group were
      treated at pasture with ivermectin when one of the following thresholds was met:
      (1) positive for lungworm larvae using the modified Baermann technique or (2)
      positive or negative for lungworm larvae using the modified Baermann technique
      with plasma pepsinogen concentration (PP) >= two international units of
      tyrosine/litre and faecal egg count (FEC) >= 200 strongyle eggs per gram of
      faeces. Calves were rotationally grazed from July 3rd 2012 (day 0) to November
      2nd 2012 (day 122) when calves were housed. Calves were weighed and sampled
      (blood and faecal) every three weeks. There was an effect of treatment and time
      on both FEC [treatment (P=0.023), time (P<0.001)] and PP [treatment (P=0.002),
      time (P<0.001)]. Both FEC and PP were higher in TST calves. There was a 50%
      reduction in anthelmintic use in TST calves compared to control calves. Clinical
      signs of lungworm infection, confirmed by the modified Baermann technique, were
      evident in TST calves on days 62 and 63 of the study. The average daily live
      weight gain for control and TST calves was 0.50 (0.02)kg day(-1) and 0.47
      (0.03)kg day(-1), respectively (P=0.41). Thus, performance in dairy calves can
      potentially be maintained with fewer anthelmintic treatments but farmers need to
      be vigilant of the challenge posed by lungworm. Any future approach into the use
      of TST in FGS calves must take into consideration the relative importance of
      lungworm as a pathogen.

PMID- 25770854
TI  - For things needing your attention: the role of neocortical gamma in sensory
      perception.
AB  - Two general classes of hypotheses for the role for gamma oscillations in
      sensation are those that predict gamma facilitates signal amplification through
      local synchronization of a distinct ensemble, and those that predict gamma
      modulates fine temporal relationships between neurons to represent information.
      Correlative evidence has been offered for and against these hypotheses. A recent
      study in which gamma was optogenetically entrained by driving fast-spiking
      interneurons showed enhanced sensory detection of harder-to-perceive stimuli,
      those that benefit most from attention, in agreement with the amplification
      hypotheses. These findings are supported by similar studies employing less
      specific optogenetic patterns or single neuron stimulation, but contrast with
      findings based on direct optogenetic stimulation of pyramidal neurons. Key next
      steps for this topic are described. 

PMID- 25770855
TI  - Correlation of brain levels of progesterone and dehydroepiandrosterone with
      neurological recovery after traumatic brain injury in female mice.
AB  - Traumatic brain injury (TBI) is an important cause of disability in humans.
      Neuroactive steroids, such as progesterone and dehydroepiandrosterone (DHEA), are
      neuroprotective in TBI models. However in order to design potential
      neuroprotective strategies based on neuroactive steroids it is important to
      determine whether its brain levels are altered by TBI. In this study we have used
      a weight-drop model of TBI in young adult female mice to determine the levels of
      neuroactive steroids in the brain and plasma at 24h, 72 h and 2 weeks after
      injury. We have also analyzed whether the levels of neuroactive steroids after
      TBI correlated with the neurological score of the animals. TBI caused
      neurological deficit detectable at 24 and 72 h, which recovered by 2 weeks after
      injury. Brain levels of progesterone, tetrahydroprogesterone (THP),
      isopregnanolone and 17beta-estradiol were decreased 24h, 72 h and 2 weeks after
      TBI. DHEA and brain testosterone levels presented a transient decrease at 24h
      after lesion. Brain levels of progesterone and DHEA showed a positive correlation
      with neurological recovery. Plasma analyses showed that progesterone was
      decreased 72 h after lesion but, in contrast with brain progesterone, its levels
      did not correlate with neurological deficit. These findings indicate that TBI
      alters the levels of neuroactive steroids in the brain with independence of its
      plasma levels and suggest that the pharmacological increase in the brain of the
      levels of progesterone and DHEA may result in the improvement of neurological
      recovery after TBI.

PMID- 25770856
TI  - Ongoing episode of major depressive disorder is not associated with elevated
      plasma levels of kynurenine pathway markers.
AB  - BACKGROUND: It has been suggested that the development of depressive symptoms as
      a result of cytokine therapy is attributable to cytokine-induced elevated
      activity of the kynurenine pathway. The few studies of this mechanism in patients
      with common major depressive disorder (MDD) have yielded inconsistent results.
      The aim of the present study was to identify markers of the kynurenine pathway in
      a clinical MDD sample with increased cytokine levels. METHODS: Fifty medication
      free MDD patients with a depressive episode and 34 healthy controls were included
      at baseline; the patients were followed for 12 weeks. Before initiating
      treatment, the patients were diagnosed and assessed for depressive symptoms and
      their blood was analyzed for tryptophan and its metabolites in the kynurenine
      pathway. The clinical assessments and metabolite measurements were repeated after
      12 weeks of "treatment as usual". RESULTS: We did not find significant elevation
      of kynurenine plasma markers in patients with a depressive episode compared to
      healthy controls, despite elevated cytokine levels in the patients. Clinical
      depression scores were significantly reduced after 12 weeks, but no significant
      change in the plasma kynurenine pathway plasma markers was observed. CONCLUSION:
      The obtained results do not support the hypothesis that MDD depressive episodes
      are associated with elevated activity in the kynurenine pathway. This suggests
      that the pathophysiology underlying depressive episodes in common MDD differs
      from that of interferon induced depression. Our results warrant further study of
      the interplay between the kynurenine pathway and the cytokine activation patterns
      in these conditions.

PMID- 25770857
TI  - Characterization of strong (241)Am sources.
AB  - Gamma ray spectra of strong (241)Am sources may reveal information about the
      source composition as there may be other radioactive nuclides such as progeny and
      radioactive impurities present. In this work the possibility to use gamma
      spectrometry to identify inherent signatures in (241)Am sources in order to
      differentiate sources from each other, is investigated. The studied signatures
      are age, i.e. time passed since last chemical separation, and presence of
      impurities. The spectra of some sources show a number of Doppler broadened peaks
      in the spectrum which indicate the presence of nuclear reactions on light
      elements within the sources. The results show that the investigated sources can
      be differentiated between by age and/or presence of impurities. These spectral
      features would be useful information in a national nuclear forensics library
      (NNFL) in cases when the visual information on the source, e.g. the source
      number, is unavailable. 

PMID- 25770858
TI  - Estimation of photoneutron intensities around radiotherapy linear accelerator 23
      MV photon beam.
AB  - CR-39 solid-state nuclear track detectors (SSNTDs) were used to study the
      variations of fast neutron relative intensities around a high-energy (23MV)
      linear accelerator (Varian 21EX) photon beam. The variations were determined on
      the patient plane at 0, 50, 100, 150 and 200cm from the isocenter of the photon
      beam. In addition, photoneutron intensities and distributions at isocenter level
      with field size of 40*40cm(2) at Source Axis Distance (SAD)=100cm around 23MV
      photon beam were also determined. The results showed that the photoneutron
      intensities decreased rapidly by increasing the distance from the center of the x
      ray beam towards the periphery, for the open fields. 

PMID- 25770859
TI  - A comparative study between the dynamic method and passive can technique of radon
      exhalation measurements from samples.
AB  - A comparative study has been carried out between the SSNTD based 'can' technique
      and active monitors based dynamic method using nine different samples, eight of
      granite and one of phosphogypsum. Besides radon ((222)Rn) exhalation,
      thoron((220)Rn) exhalation and (226)Ra and (232)Th content were also measured.
      The results are: (i) presence of significant thoron exhalation from samples and
      (ii) observation of thoron interference and leak (~0.05h(-1)) from the 'can' in
      the SSNTD based 'can' technqiue. The study unequivocally demonstrates the
      presence of intrinsic uncertainty in SSNTD based 'can' technique. Instead,
      dynamic method offers a more reliable and faster method. 

PMID- 25770860
TI  - Varied uses of the medial sural artery perforator flap.
AB  - BACKGROUND AND AIM: The aim of the study was to demonstrate how the medial sural
      artery perforator flap can be used in a wide range of settings and not focused on
      one area, as previous papers have done. We also wanted to demonstrate that larger
      flaps can be harvested from the donor site and still closed directly to optimise
      the appearance of the donor site. METHODS: We describe the use of the medial
      sural artery perforator flap in 18 patients with defects of the head and neck,
      upper and lower limbs. RESULTS: All 18 flaps survived, although one suffered some
      delayed partial loss due to pressure damage. All donor sites were closed directly
      to optimise the appearance of the donor site. There were complications with the
      donor site wound in 2 patients. This resulted in further surgery in one case.
      CONCLUSION: The advantages of the flap are discussed over some of the more
      commonly used options for reconstruction of these areas. It is a good source of
      thin, pliable soft tissue with a long pedicle, which makes it very adaptable. The
      skin paddle is small but if designed appropriately allows the donor site to be
      closed directly, leaving an aesthetically good result.

PMID- 25770861
TI  - Testing for local host-parasite adaptation: an experiment with Gyrodactylus
      ectoparasites and guppy hosts.
AB  - Hosts and parasites are in a perpetual co-evolutionary "arms race". Due to their
      short generation time and large reproductive output, parasites are commonly
      believed to be ahead in this race, although increasing evidence exists that
      parasites are not always ahead in the arms race - in part owing to evolutionary
      lineage and recent ecological history. We assess local adaptation of hosts and
      parasites, and determine whether adaptation was influenced by ecological or
      evolutionary history, using full reciprocal cross-infections of four Gyrodactylus
      ectoparasite populations and their four guppy (Poecilia reticulata) host
      populations in Trinidad. To consider effects of evolutionary lineage and recent
      ecology, these four populations were collected from two different river drainages
      (Marianne and Aripo) and two different predation environments (high and low). The
      highest infection levels were obtained when parasites from the Aripo lineage
      infected guppies from the Marianne lineage, indicating a higher infectivity,
      virulence and/or reproductive success of the Aripo parasites. Aripo lineage
      guppies were also better able to limit Gyrodactylus population growth than
      guppies from the Marianne River, indicating their strong "resistance" to
      Gyrodactylus regardless of the source of the parasite. Predation environment had
      no detectable influence on host-parasite population dynamics of sympatric or
      allopatric combinations. The much stronger effect of evolutionary lineage (i.e.,
      river) than recent ecological history (i.e., predation) emphasises its importance
      in driving co-evolutionary dynamics, and should be explored further in future
      studies on local host-parasite adaptation.

PMID- 25770862
TI  - Is Drain Tip Culture Prognostic of Surgical Site Infection? Results of 1380 Drain
      Tip Cultures in Total Hip Arthroplasty.
AB  - The purpose of this study was to evaluate a prognostic value of drain tip culture
      for surgical site infection (SSI) after total hip arthroplasty. A total of 1380
      closed suction drain tips cultured after removal in primary total hip
      arthroplasty were included in this study. Drains were removed in 12-72 hours
      after surgery. Drain tip cultures were positive in 11 cases (0.8%). SSI was found
      in 4 cases (0.3%), where the drain tip cultures were all negative. The
      sensitivity of drain tip culture for infection after surgery was 0%, and the
      specificity was 99.7%. We concluded that, drain tip culture cannot be prognostic
      for SSI after total hip arthroplasty. Routine use of drain tip culture is not
      supported.

PMID- 25770863
TI  - Tourniquet Release Prior to Dressing Application Reduces Blistering Following
      Total Knee Arthroplasty.
AB  - Skin blisters occur in up to 20% of patients after total knee arthroplasty (TKA).
      Tourniquet release results in a limb volume increase of 10%. We hypothesized that
      releasing tourniquet before application of circumferential dressing will decrease
      blister formation. A prospective study was conducted on 135 consecutive primary
      TKAs. The tourniquet was released immediately after wound closure to allow for re
      perfusion and then a dressing was applied. These patients were compared to a
      historical cohort of 200 primary TKAs, where the tourniquet was released after
      application of dressing. There was a significant difference in the incidence of
      blisters between the two groups [Late 7.5% (15/200) vs early release 2.2% (3/135)
      P=0.028]. Releasing the tourniquet prior to dressing application has reduced the
      incidence of blistering following TKA. 

PMID- 25770864
TI  - Hospital Acquired Conditions Are the Strongest Predictor for Early Readmission:
      An Analysis of 26,710 Arthroplasties.
AB  - Hospital readmission is a metric of hospital quality of care, yet little is known
      what factors predict hospital readmission following arthroplasty. Our aim was to
      identify variables associated with early readmission following knee and hip
      arthroplasty, with focus upon hospital acquired conditions (HACs). Retrospective
      cohort analysis using Surgical Care Improvement Project (SCIP) and Veteran's
      Affairs Surgical Quality Improvement Program (VASQIP) data was performed over a
      five-year period. Following 26,710 total and partial primary arthroplasties
      (16,808 knees and 9902 hips), the overall 30-day readmission was 7.3% (1940) with
      readmission rates of 6.6% for knee arthroplasty and 8.4% for hip arthroplasty.
      HACs accounted for 42% of all complications and were the strongest predictor of
      readmission. Efforts to reduce these events may improve cost and safety of
      arthroplasty. 

PMID- 25770865
TI  - The Divergence of Wear Propagation and Stress at Steep Acetabular Cup Positions
      Using Ceramic Heads and Sequentially Cross-Linked Polyethylene Liners.
AB  - The aim of the present wear simulator study was to assess the effect of steep
      acetabular cup positions on the wear propagation of highly cross-linked-PE (HX
      PE) liners. Furthermore, a finite element analysis (FEA) was performed in order
      to calculate the stress within the HX-PE material in case of steep cup positions
      under physiological loadings. The higher stress in the HX-PE at a steep
      acetabular cup position did not result in increased wear in the present wear
      simulator study. The gravimetrical wear rates at normal (45 degrees ) and steep
      cup inclinations (75 degrees ) showed wear amounts of 3.15+/-0.27mg and 2.18+/
      0.31mg per million cycles (p=0.028), respectively. However, FEA revealed clear
      increase in stress at the HX-PE liners with respect to steep cup positions. 

PMID- 25770866
TI  - Short Term Outcomes of a Hydroxyapatite Coated Metal Backed Patella.
AB  - We retrospectively evaluated the records and radiographs of 101 knees with a
      hydroxyapatite coated metal backed patella (HAP) and 50 knees with a cemented
      polyethylene patella (CP) with minimum two year clinical follow up. There were no
      patellar revisions during the study period. Patients in both the HAP and CP
      groups had similar clinical outcomes at final follow-up. Forty-five percent of
      patients in the HAP group had 1-2mm areas of decreased trabecular bone density
      around the pegs, which were not observed in the CP group, and may represent
      stress shielding. This uncemented HAP component has satisfactory early clinical
      outcomes, but long-term follow up is necessary to determine the durability of
      this implant. 

PMID- 25770867
TI  - Folate supplements for stroke prevention: targeted trial trumps the rest.

PMID- 25770868
TI  - Differences in cervical multifidus muscle thickness during isometric contraction
      of shoulder muscles: a comparison between patients with chronic neck pain and
      healthy controls.
AB  - OBJECTIVE: The purposes of this study were to (1) measure the thickness of
      cervical multifidus muscle (CMM) in different maximal voluntary contraction
      percentages of isometric contraction of shoulder muscles, (2) evaluate the
      differences of the CMM thickness in different directions of the shoulder
      movement, and (3) compare the changes in the CMM thickness of participants with
      neck pain and also of healthy individuals. METHODS: Twenty healthy men (age,
      27.45 +/- 4.37 years; height, 177 +/- 4.66 cm; weight, 72.85 +/- 6.46 kg) and 20
      men with chronic mechanical neck pain (age, 28.90 +/- 5.53 years; height, 176 +/-
      5.98 cm; weight, 73.15 +/- 7.82 kg) participated in the study. Both the right and
      left CMM thicknesses were measured using an ultrasound device while participants
      performed isometric contraction of shoulder muscles in 6 movement directions.
      RESULTS: In both groups, an increment of CMM thickness followed as the increase
      of isometric force (P < .01).The increase of muscle thickness of healthy
      participants was substantially more than the chronic mechanical neck pain
      participants (P = .03). Although no significant difference of CMM thickness was
      seen among the effects of the 6 force directions (P > .05), there was a
      significant difference of activity noted between the left and right sides (P =
      .047). CONCLUSION: The results of the present study indicate that isometric
      contraction of shoulder muscles caused an increase in the CMM thickness
      regardless of force direction. This increase was seen in both groups of healthy
      participants and patients with neck pain. However, less thickness changes were
      observed in participants with neck pain, which may be interpreted as reduced CMM
      activity in such people.

PMID- 25770869
TI  - Distinct facets of impulsivity exhibit differential associations with substance
      use disorder treatment processes: a cross-sectional and prospective investigation
      among military veterans.
AB  - Impulsivity, a multi-faceted construct characterized by rash, unplanned actions
      and a disregard for long-term consequences, is associated with poor substance use
      disorder (SUD) treatment outcomes. Little is known though about the influence of
      impulsivity on treatment process variables critical for initiating and
      maintaining behavioral change. This knowledge gap is important as different
      aspects of impulsivity may be susceptible to diverse cognitive, behavioral and
      pharmacological influences. The present study examined two distinct facets of
      impulsivity (lack of planning and immoderation--a proxy of urgency) as predictors
      of processes that impact SUD treatment success (active coping, avoidant coping,
      self-efficacy, and interpersonal problems). Participants were 200 Veterans who
      completed impulsivity and treatment process assessments upon entering an SUD
      treatment program and treatment process assessments at treatment discharge.
      Results from multivariate models revealed that lack of planning was associated
      with lower active coping and higher avoidant coping and interpersonal problems at
      intake, though not with lower self-efficacy to abstain from substances.
      Immoderation was associated with higher avoidant coping and lower self-efficacy
      to abstain from substances at intake, but not with lower active coping or higher
      interpersonal problems. Higher immoderation, but not lack of planning, predicted
      lower self-efficacy to abstain from substances at treatment discharge. These
      findings suggest that different facets of impulsivity confer risk for different
      SUD treatment process indicators and that clinicians should consider the
      behavioral expression of patients' impulse control problems in treatment planning
      and delivery.

PMID- 25770870
TI  - Adapting the helpful responses questionnaire to assess communication skills
      involved in delivering contingency management: preliminary psychometrics.
AB  - A paper/pencil instrument, adapted from Miller and colleagues' (1991) Helpful
      Responses Questionnaire (HRQ), was developed to assess clinician skill with core
      communicative aspects involved in delivering contingency management (CM). The
      instrument presents a single vignette consisting of six points of client dialogue
      to which respondents write 'what they would say next.' In the context of an
      implementation/effectiveness hybrid trial, 19 staff clinicians at an opiate
      treatment program completed serial training outcome assessments before,
      following, and three months after CM training. Assessments included this
      adaptation of the HRQ, a multiple-choice CM knowledge test, and a recorded
      standardized patient encounter scored for CM skillfulness. Study results reveal
      promising psychometric properties for the instrument, including strong scoring
      reliability, internal consistency, concurrent and predictive validity, test
      retest reliability and sensitivity to training effects. These preliminary
      findings suggest the instrument is a viable, practical method to assess clinician
      skill in communicative aspects of CM delivery. 

PMID- 25770871
TI  - Cloning and expression analysis of a Toll-like receptor 22 (tlr22) gene from
      turbot, Scophthalmus maximus.
AB  - Toll-like receptor 22 (TLR22) exists exclusively in aquatic animals and
      recognizes double stranded RNA (dsRNA). In the present study, a tlr22 gene and
      its 5'-flanking sequence were cloned from turbot, Scophthalmus maximus, its
      immune responsive expression was subsequently studied in vivo. The turbot
      (sm)tlr22 gene spans over 5.6 kb with a structure of 4 exon-3 intron and encodes
      962 amino acids. The deduced protein shows the highest sequence identity (76.7%)
      to Japanese flounder Tlr22 and possesses a signal peptide sequence, a leucine
      rich repeat (LRR) domain composed of 27 LRR motifs, a transmembrane region and a
      Toll/interleukin-1 receptor (TIR) domain. Phylogenetic analysis grouped it with
      other teleost Tlr22s. The interferon-stimulated response element (ISRE) and
      signal transducer and activator of transcription (STAT) binding site important
      for the basal transcriptional activity of TLR3 were predicted in the 5'-flanking
      sequence of smtlr22 gene. Quantitative real-time PCR (qPCR) analysis demonstrated
      the constitutive expression of smtlr22 mRNA in all examined tissues with higher
      levels in the head kidney, kidney and spleen. Further, smtlr22 expression was
      significantly up-regulated following challenge with polyinosinic: polycytidylic
      acid (poly I:C), lipopolysaccharide (LPS) or turbot reddish body iridovirus
      (TRBIV) in the gills, head kidney, spleen and muscle, with maximum increases
      ranging from 2.56 to 6.24 fold upon different immunostimulants and organs. These
      findings suggest a possible role of Smtlr22 in the immune responses to the
      infections of a broad range of pathogens that include DNA and RNA viruses and
      Gram-negative bacteria. 

PMID- 25770872
TI  - Target delineation variability and corresponding margins of peripheral early
      stage NSCLC treated with stereotactic body radiotherapy.
AB  - PURPOSE: To quantify the target delineation variability in peripheral early stage
      lung cancer treated with SBRT and derive corresponding margins. METHODS AND
      MATERIALS: Sixteen early stage NSCLC GTV's were delineated by 11 radiation
      oncologists from 4 institutes. A median surface was computed and the delineation
      variation perpendicular to this surface was measured (local standard
      deviation=SD). The overall target delineation variability was quantified by the
      root-mean-square (rms) of the local SD. The required margin was determined by
      expanding all delineations to encompass the median surface, where after the
      underlying probability distribution was modeled by a number of uncorrelated
      'pimples-and-dimples'. RESULTS: The overall target delineation variability was
      2.1mm (rms). Institute I-III delineated significantly smaller volumes than
      institute IV, yielding target delineation variabilities of 1.2mm and 1.8mm
      respectively. The margin required to obtain 90% coverage of the delineated
      contours was 3.4mm and 5.9mm respectively. The factor alpha in M=alphaSigma
      required to calculate adequate margins was 2.8-3.2, which is larger than the 2.5
      found for 3D rigid target displacement. CONCLUSION: A relatively small target
      delineation uncertainty of 1.2mm-1.8mm (1SD) was observed for early stage NSCLC.
      A 3.4-5.9mm GTV-to-PTV margin was required to account for this uncertainty alone,
      ignoring other sources of geometric uncertainties.

PMID- 25770873
TI  - Level IIb CTV delineation based on cervical fascia anatomy in nasopharyngeal
      cancer.
AB  - We carefully reviewed magnetic resonance (MR) images from 100 consecutive NPC
      patients and analyzed the lymph node distribution status at level IIb. We
      proposed several modifications of the existing consensus guidelines for
      determining the level IIb clinical target volume (CTV) in NPC patients. 

PMID- 25770874
TI  - Integrated prostate cancer centers might cause an overutilization of radiotherapy
      for low-risk prostate cancer: A comparison of treatment trends in the United
      States and Germany from 2004 to 2011.
AB  - INTRODUCTION: Aim of the study was to analyze changes in primary treatment for
      low-risk prostate cancer across different healthcare systems. MATERIALS AND
      METHODS: We compared "Surveillance Epidemiology and End Results" data (USA) with
      data from four German federal epidemiological cancer registries, both from 2004
      to 2011. We excluded metastatic disease and patients aged ?80 years. Thereof, we
      identified 132,506 (USA) and 54,159 (Germany) patients with low-risk according to
      the 2014 EAU guidelines. We tested treatment trends for statistical significance
      with a linear regression model. RESULTS: Active treatment was radical
      prostatectomy (RP) in 36.1% vs. 66.2% and radiotherapy (RT) in 38.4% vs. 11.8%.
      No active treatment (NAT) was reported in 24.2% vs. 16.2% (p<0.001 each). Through
      the study period the use of RP decreased from 37.1% to 34.2% in the USA (p=0.04)
      and was constant at a mean of 66.2% in Germany (p=0.8). The use of RT in the USA
      decreased from 42.8% to 31.8% (p<0.001), while it was stable in Germany (p=0.09).
      The NAT group grew from 18.0% to 33.2% in the USA (p<0.001), while it was stable
      in Germany until 2009 (p=0.3). From 2009 to 2011 there also was an increase of
      the NAT group in Germany from 15.2% to 19.4% (p=0.001). CONCLUSION: In contrast
      to former evidence we found the relative use of RT for low-risk prostate cancer
      much higher in the USA compared to Germany. The implementation of integrated
      prostate cancer centers in the USA might explain this observation. Deferred and
      defensive treatment strategies showed a steady increase in the USA. This
      development seems delayed in Germany by several years.

PMID- 25770875
TI  - High dose-rate brachytherapy boost for intermediate risk prostate cancer: Long
      term outcomes of two different treatment schedules and early biochemical
      predictors of success.
AB  - BACKGROUND AND PURPOSE: To report long-term cancer control rates following high
      dose-rate (HDR) brachytherapy boost for intermediate risk prostate cancer and
      explore early biochemical predictors of success. MATERIAL AND METHODS: Results of
      two sequential phase II trials are updated and compared: (1) Single 15 Gy HDR
      boost followed by external beam radiotherapy (EBRT) 37.5 Gy/15fractions, (2) Two
      HDR fractions of 10 Gy followed by EBRT 45 Gy/25fractions. Patients were followed
      prospectively for clinical and biochemical outcomes. Nadir PSA (nPSA) and PSA at
      3-years were analyzed as continuous variables, and ROC analysis was used to
      identify the optimal cutoff values. Kaplan-Meier bDFS curves were generated and
      the log-rank test used to compare different groups RESULTS: 183 patients were
      accrued; 123 to the single fraction trial and 60 to the standard fractionation
      trial, with a median follow-up of 74 months and 99 months, respectively. The 5
      year biochemical relapse-free survival was 97.4% and 92.7%, respectively
      (p=0.995). Median nPSA was 0.08 ng/ml. Failure to achieve a nPSA <0.4 ng/ml was
      associated with a significantly higher rate of biochemical relapse (5-year bDFS:
      100% vs. 72%; p<0.0001). CONCLUSION: HDR boost with single fraction 15 Gy
      provides durable long-term biochemical disease-free survival. PSA nadir <0.4
      ng/ml is associated with very low risk of biochemical failure.

PMID- 25770876
TI  - Activation of the Nrf2 defense pathway contributes to neuroprotective effects of
      phloretin on oxidative stress injury after cerebral ischemia/reperfusion in rats.
AB  - Oxidative stress is considered a major contributing factor in cerebral
      ischemia/reperfusion injury. Phloretin, a dihydrochalcone belonging to the
      flavonoid family, is particularly rich in apples and apple-derived products. A
      large body of evidence demonstrates that phloretin exhibits anti-oxidant
      properties, and phloretin has potential implications for treating oxidative
      stress injuries in cerebral ischemia/reperfusion. Therefore, the neuroprotective
      and antioxidant effects of phloretin against ischemia/reperfusion injury, as well
      as related probable mechanisms, were investigated. The cerebral
      ischemic/reperfusion injury model was reproduced in male Sprague-Dawley rats
      through middle cerebral artery occlusion. At 24h after reperfusion, neurological
      score, infarct volume, and brain water content were assessed. Oxidative stress
      was evaluated by superoxide dismutases (SOD), glutathione (GSH), glutathione
      peroxidase (GSH-Px), and malondialdehyde (MDA) levels. Nrf2 expression was
      measured by RT-PCR and western blot. Consequently, results showed that phloretin
      pretreatment for 14days significantly reduced infarct volume and brain edema, and
      ameliorated neurological scores in focal cerebral ischemia/reperfusion rats. SOD,
      GSH and GSH-Px activities were greatly decreased, and MDA levels significantly
      increased after ischemia/reperfusion injury. However, phloretin pretreatment
      dramatically suppressed these oxidative stress processes. Furthermore, phloretin
      upregulated Nrf2 mRNA and protein expression of in ischemia/reperfusion brain
      tissue. Taken together, phloretin exhibited neuroprotective effects in cerebral
      ischemia/reperfusion, and the mechanisms are associated with oxidative stress
      inhibition and Nrf2 defense pathway activation. 

PMID- 25770877
TI  - Motor neuron dysfunctions in the frontotemporal lobar degeneration spectrum: a
      clinical and neurophysiological study.
AB  - BACKGROUND: Although only a few frontotemporal lobar degeneration (FTLD) patients
      develop frank amyotrophic lateral sclerosis (ALS), motor neuron dysfunctions
      (MNDys) occur in a larger proportion of patients. The aim of this study is to
      evaluate MNDys and ALS in a sample of consecutively enrolled sporadic FTLD
      patients. METHODS: Clinical and neurophysiological evaluations (i.e. needle
      electromyography) assessed lower (LMN) and upper (UMN) motor neuron function at
      the baseline in 70 probable FTLD patients (i.e., 26 behavioural variant-bvFTD, 20
      primary progressive aphasias-PPAs and 24 corticobasal syndrome-CBS). To obtain a
      more accurate estimation, quantitative scales were also applied (i.e. ALSFRS-r
      and UMN scale). Patients were screened for MAPT, GRN and C9orf72 mutations. A
      mean clinical follow-up of 27.8+/-22.4 months assessed MNDys progression and the
      clinical presentation of ALS. RESULTS: Five genetic cases were identified. Within
      the sample of sporadic patients, a relative low rate of FTLD patients was
      diagnosed as probable ALS (5%), while a higher proportion of patients (17%)
      showed clinical and neurophysiological MNDys. Thirteen patients (20%) presented
      with isolated clinical signs of LMN and/or UMN dysfunction, and 8 patients (12%)
      showed neurogenic changes at the electromyography. No differences in FTLD
      phenotype and disease duration were found between MNDys positive and negative
      patients. Clinical MNDys were highly associated with positive electromyographic
      findings. At follow-up, no MNDys positive patient developed ALS. CONCLUSION:
      Neurophysiological and clinical examinations revealed mild MNDys in FTLD patients
      not fulfilling criteria for ALS. This condition did not evolve at a mean follow
      up of two years. These results, indicating a subclinical degeneration of
      corticospinal tracts and lower motor neurons, suggest that FTLD patients may be
      more at risk of MNDys than the general population.

PMID- 25770878
TI  - Cauda equina conduction time in Guillain-Barre syndrome.
AB  - The proximal segment of peripheral nerves is assumed to be involved in both
      demyelinating and axonal types of Guillain-Barre syndrome (GBS). However,
      electrophysiological examinations have not yet clarified if this segment is
      involved. We measured cauda equina conduction time (CECT) in nine demyelinating
      GBS and seven axonal GBS patients. Compound muscle action potentials (CMAPs) were
      recorded from the abductor hallucis muscle. Electrical stimulation was given at
      the ankle and the knee, and magnetic stimulation was given over the first sacral
      (S1) and first lumbar (L1) spinous processes using a magnetic augmented
      translumbosacral stimulation (MATS) coil. CECT was obtained by subtracting S1
      level latency from L1-level latency. CECT was prolonged in all the patients with
      demyelinating GBS who had leg symptoms, whereas motor conduction velocity (MCV)
      at the peripheral nerve trunk was normal in all the patients. In all the patients
      with axonal GBS having leg symptoms, CECT and MCV were normal and no conduction
      blocks were detected between the ankle and the neuro-foramina. The cauda equina
      is much more frequently involved than the peripheral nerve trunk in demyelinating
      GBS. In axonal GBS, usually, CECT is normal and segmental lesions are absent
      between the ankle and the neuro-foramina. Therefore, the CECT measurement should
      be very useful for directly detecting demyelinating lesions in GBS. 

PMID- 25770879
TI  - Ingenol mebutate gel for actinic keratosis: the link between quality of life,
      treatment satisfaction, and clinical outcomes.
AB  - BACKGROUND: Actinic keratosis therapy can elicit unsightly and painful local skin
      responses; assessment of treatment satisfaction and health-related quality of
      life (QoL) is important. Ingenol mebutate gel is a novel topical field therapy
      for actinic keratosis. OBJECTIVE: Post-hoc analyses were performed based on
      patient-reported outcomes from phase-III trials (n = 1005) to assess the effects
      of ingenol mebutate on QoL and the relationship between both QoL and treatment
      satisfaction, and degree of lesion clearance. METHODS: Patients received ingenol
      mebutate or vehicle for self-application to a 25-cm(2) contiguous area: 0.015%
      once daily for 3 consecutive days (face/scalp) or 0.05% once daily for 2
      consecutive days (trunk/extremities). QoL (Skindex-16) and Treatment Satisfaction
      Questionnaire for Medication data were recorded. RESULTS: Significant, positive
      associations between Treatment Satisfaction Questionnaire for Medication score
      and degree of clearance were identified for patients in the face/scalp
      (effectiveness P < .0001 and global satisfaction P = .0002) and trunk/extremities
      (P < .0001 and P = .0014, respectively) groups. There was a significant
      association between Skindex-16 score and clearance for patients in the face/scalp
      group for change in symptoms (P = .0218), emotions (P = .0002), and overall
      Skindex-16 score (P = .0006) from baseline. LIMITATIONS: Clinical trial
      population findings may not be generalizable to clinical practice. CONCLUSION:
      Ingenol mebutate significantly improved patients' QoL and treatment satisfaction.
      Improvements were associated with higher degrees of actinic keratosis lesion
      clearance.

PMID- 25770880
TI  - WITHDRAWN: Pulmonary Hemorrhage in a Patient With ST-segment Elevation Acute
      Myocardial Infarction Treated With Ticagrelor: A Case Report.
AB  - This article has been withdrawn at the request of the 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- 25770881
TI  - Coronary Disease Deaths: From Birth Cohorts to Prevention.

PMID- 25770882
TI  - Endovascular Carotid Revascularization Performed by a Multidisciplinary Team:
      First Experience in Spain.

PMID- 25770883
TI  - [Use of chemotherapy and radiotherapy in the treatment of urothelial carcinoma of
      the upper urinary tract].
AB  - Urothelial carcinomas of the upper urinary tract are rare entities. Surgery
      remains the mainstay of the management. The use of others therapeutic modalities
      is not clearly defined yet. However, the frequency of local recurrence and
      locoregional encourage us to evaluate the indication of adjuvant therapies. We
      conducted a synthesis of key data in the literature on the use of chemotherapy
      and radiotherapy in the treatment of urothelial carcinoma of the renal pelvis and
      ureter. A literature search on PubMed was performed using the following keywords
      (MeSH) "urothelial carcinoma", "upper urinary tract", "radiation",
      "chemotherapy", and adjuvant. 

PMID- 25770885
TI  - Patent femoro-popliteal vein bypass with occlusion of common and external iliac
      arteries.

PMID- 25770884
TI  - [Management of locally advanced anal canal carcinoma with modulated arctherapy
      and concurrent chemotherapy].
AB  - The standard treatment of locally advanced (stage II and III) squamous cell
      carcinoma of the anal canal consists of concurrent chemoradiotherapy (two cycles
      of 5-fluoro-uracil, mitomycin C, on a 28-day cycle), with a dose of 45 Gy in 1.8
      Gy per fraction in the prophylactic planning target volume and additional 14 to
      20 Gy in the boost planning target volume (5 days per week) with a possibility of
      15 days gap period between the two sequences. While conformal irradiation may
      only yield suboptimal tumor coverage using complex photon/electron field
      junctions (especially on nodal areas), intensity modulated radiation therapy
      techniques (segmented static, dynamic, volumetric modulated arc therapy and
      helical tomotherapy) allow better tumour coverage while sparing organs at risk
      from intermediate/high doses (small intestine, perineum/genitalia, bladder,
      pelvic bone, etc.). Such dosimetric advantages result in fewer severe acute
      toxicities and better potential to avoid a prolonged treatment break that
      increases risk of local failure. These techniques also allow a reduction in late
      gastrointestinal and skin toxicities of grade 3 or above, as well as better
      functional conservation of anorectal sphincter. The technical achievements
      (simulation, contouring, prescription dose, treatment planning, control quality)
      of volumetric modulated arctherapy are discussed.

PMID- 25770886
TI  - Changes in prevalence of diabetic complications and associated healthcare costs
      during a 10-year follow-up period among a nationwide diabetic cohort.
AB  - OBJECTIVE: Long-term health and economic consequences of diabetes mellitus are of
      significant importance to health policy makers to identify the most efficient
      interventions for disease managements. However, existing data are mainly from
      simulation models instead of "real-world" data. The objective of this study was
      to longitudinally evaluate the changes of prevalence of diabetic complications
      and associated healthcare costs in a nationally-representative diabetic cohort.
      METHODS: We used the 2000-2011 Taiwan's Longitudinal Health Insurance Database
      (LHID) to conduct a population-based cohort study of 136,372 patients with type 2
      diabetes. Diabetic complications of each patient were calculated annually after
      the cohort entry by the adapted Diabetes Complications Severity Index (aDCSI)
      score (sum of diabetic complication with severity levels, range 0-13) using
      diagnostic codes recorded in the LHID. Study subjects were further categorized
      into six subgroups according to their aDCSI score (0, 1, 2, 3, 4, 5+) at cohort
      entry. Healthcare utilizations (including outpatient and inpatient visits) as
      well as direct medical costs for the six subgroups were estimated annually using
      patient-level data from the LHID. RESULTS: We found the severity of diabetic
      complications increased over time, especially for patients with aDCSI score of 2
      and above at cohort entry (at 10years of follow-up: aDCSI=0 (cohort entry), 2.37;
      aDCSI=1, 3.59; aDCSI=2, 4.60; aDCSI=3, 5.14; aDCSI=4, 5.96). There were
      significant differences in healthcare utilizations and associated medical costs
      among patients stratified by aDCSI score (e.g. at 1year after cohort entry, mean
      counts of inpatient visits: 0.14 vs. 1.81 for aDCSI=0 vs.5+). Relatively high
      healthcare utilizations and associated medical costs in the first year of cohort
      entry were observed for patients with aDCSI score of 4 and above at cohort entry.
      CONCLUSIONS: We provided the important empirical data for patient-level
      longitudinal changes in diabetic complications and associated healthcare
      utilization and medical costs among patients with diabetes.

PMID- 25770887
TI  - Bone stability around dental implants: Treatment related factors.
AB  - The bone bed around dental implants is influenced by implant and augmentation
      materials, as well as the insertion technique used. The primary influencing
      factors include the dental implant design, augmentation technique, treatment
      protocol, and surgical procedure. In addition to these treatment-related factors,
      in the literature, local and systemic factors have been found to be related to
      the bone stability around implants. Bone is a dynamic organ that optimises itself
      depending on the loading condition above it. Bone achieves this optimisation
      through the remodelling process. Several studies have confirmed the importance of
      the implant design and direction of the applied force on the implant system.
      Equally dispersed strains and stresses in the physiological range should be
      achieved to ensure the success of an implant treatment. If a patient wishes to
      accelerate the treatment time, different protocols can be chosen. However, each
      one must consider the amount and quality of the available local bone. Immediate
      implantation is only successful if the primary stability of the implant can be
      provided from residual bone in the socket after tooth extraction. Immediate
      loading demands high primary stability and, sometimes, the distribution of
      mastication forces by splinting or even by inserting additional implants to
      ensure their success. Augmentation materials with various properties have been
      developed in recent years. In particular, resorption time and stableness affect
      the usefulness in different situations. Hence, treatment protocols can optimise
      the time for simultaneous implant placements or optimise the follow-up time for
      implant placement. 

PMID- 25770888
TI  - Outcomes of Modestly Hypofractionated Radiation for Lung Tumors: Pre- and Mid
      Treatment Positron Emission Tomography-Computed Tomography Metrics as Prognostic
      Factors.
AB  - Many patients with lung tumors have tumors too large for stereotactic ablative
      radiotherapy and comorbidities precluding concurrent chemotherapy. We report the
      outcomes of 29 patients treated with hypofractionated radiotherapy (RT) to 60 to
      66 Gy in 3-Gy fractions. We also report an exploratory analysis of the prognostic
      value of the pre- and mid-RT positron emission tomography-computed tomography.
      INTRODUCTION: Modestly hypofractionated radiation therapy (HypoRT; 60-66 Gy in 3
      Gy fractions) allows patients with locally advanced thoracic tumors and poor
      performance status to complete treatment within a shorter period without
      concurrent chemotherapy. We evaluated the outcomes and imaging prognostic factors
      of HypoRT. MATERIALS AND METHODS: We retrospectively reviewed the data from all
      patients with primary and metastatic intrathoracic tumors treated with HypoRT
      from 2006 to 2012. We analyzed the survival and toxicity outcomes, including
      overall survival (OS), progression-free survival (PFS), local recurrence (LR),
      and distant metastasis. We also evaluated the following tumor metrics in an
      exploratory analysis: gross tumor volume (GTV), maximum standardized uptake value
      (SUVMax), and metabolic tumor volume using a threshold of >= 50% of the SUVMax
      (MTV50%) or the maximum gradient of fluorine-18 fluorodeoxyglucose uptake
      (MTVEdge). We assessed the association of these metrics and their changes from
      before to mid-RT using positron emission tomography-computed tomography (PET-CT)
      with OS and PFS. RESULTS: We identified 29 patients, all with pre-RT and 20 with
      mid-RT PET-CT scans. The median follow-up period was 15 months. The 2-year
      overall and non-small-cell lung cancer-only rate for OS, PFS, and LR, was 59% and
      59%, 52% and 41%, and 27% and 32%, respectively. No grade >= 3 toxicities
      developed. The median decrease in GTV, SUVMax, and MTVEdge was 11%, 24%, and 18%,
      respectively. Inferior OS was associated with a larger pre-RT MTVEdge (P = .005)
      and pre-RT MTV50% (P = .007). Inferior PFS was associated with a larger mid-RT
      SUVMax (P = .003). CONCLUSION: These findings add to the growing body of data
      demonstrating promising outcomes and limited toxicity with HypoRT. The pre- and
      mid-RT PET-CT metrics could be useful for prognostic stratification in future
      clinical trials.

PMID- 25770889
TI  - Hard and soft tissue surgical complications in dental implantology.
AB  - This article discusses surgical complications associated with the placement of
      dental implants, specifically focusing on how they occur (etiology), as well as
      their management and prevention. Dental implant surgical complications can be
      classified into those of hard and soft tissues. In general, complications can be
      avoided with thorough preoperative treatment planning and proper surgical
      technique.

PMID- 25770890
TI  - In vitro inhibition of field isolates of feline calicivirus with short
      interfering RNAs (siRNAs).
AB  - Feline calicivirus (FCV) is a common infection of domestic cats. Most infections
      are mild and self-limiting; however more severe disease manifestations, such as
      FCV-associated virulent systemic disease, may be associated with significant
      morbidity and mortality. There is currently a lack of effective antiviral
      treatments for these disease manifestations. In this study, a panel of eight
      siRNAs were designed to target four conserved regions of the FCV genome. siRNAs
      were screened for in vitro antiviral efficacy against the reference strain FCV F9
      by determination of extracellular virus titres and morphological assessment of
      protection from cytopathic effect. Three of the siRNA (FCV3.7, FCV4.1, and
      FCV4.2) demonstrated a marked antiviral effect with a greater than 99% reduction
      in extracellular viral titre. Titration of these effective siRNAs demonstrated a
      clear concentration-response relationship, with IC50 values of approximately 1
      nM, and combination treatment with multiple siRNAs demonstrated additive or
      synergistic effects. To assess the potential usefulness of the compounds in a
      clinical setting, siRNAs were screened against a panel of six recent Australian
      FCV isolates from cats with FCV-related disease. The siRNAs shown to be effective
      against the reference strain FCV F9 were active against the majority of the
      isolates tested, although some variability was noted. Taken together these data
      suggest potential therapeutic application of antiviral RNAi for treating FCV
      associated disease in cats.

PMID- 25770891
TI  - Characterization of mucosa-associated bacterial communities in abomasal ulcers by
      pyrosequencing.
AB  - Abomasal ulcers are important pathological alterations of the gastrointestinal
      tract in cattle and are exceptionally hard to diagnose in vivo. The microbiome of
      the abomasum in cattle with or without ulcers has hardly been studied to date,
      and if so, the studies used culture-dependent methods. In the present study, the
      bacterial communities associated with abomasal ulcers of slaughter cows, bulls,
      and calves in Austria were described using 16S rRNA gene pyrosequencing.
      Sequences were clustered into 10,459 operational taxonomic units (OTUs),
      affiliating to 28 phyla with Proteobacteria, Firmicutes, Bacteroidetes and
      Tenericutes dominating (96.4% of all reads). The most abundant genera belonged to
      Helicobacter, Acetobacter, Lactobacillus, and novel Mycoplasma-like phylotypes.
      Significant differences between the microbial communities of healthy and
      ulcerated calves compared to cows and bulls could be observed. However, only few
      statistically significant differences in the abundances of certain OTUs between
      healthy and ulcerated abomasal mucosa were found. Additionally, near full-length
      16S rRNA gene sequences of the most abundant phylotypes were obtained by cloning
      and Sanger sequencing (n=88). In conclusion, our results allow the first deep
      insights into the composition of abomasal mucosal bacterial communities in cattle
      and describe a hitherto unknown high diversity and species richness of abomasal
      bacteria in cattle. Our results suggest that bacteria may have only limited
      involvement in the etiology of abomasal ulcers. However, future research will be
      needed to verify the contribution of bacteria to abomasal ulcer formation as
      presence or absence of bacteria does not necessarily correlate with etiology of
      disease. 

PMID- 25770892
TI  - Experimental susceptibility of European sea bass and Senegalese sole to different
      betanodavirus isolates.
AB  - The susceptibility of juvenile European sea bass and Senegalese sole to three
      VNNV isolates (a reassortant RGNNV/SJNNV, as well as the parental RGNNV and SJNNV
      genotypes) has been evaluated by challenges using two inoculation ways (bath and
      intramuscular injection). The results demonstrate that these two fish species are
      susceptible to all the VNNV isolates tested. In European sea bass, RGNNV caused
      the highest cumulative mortality, reaching maximum values of viral RNA and
      titres. Although the SJNNV isolate did not provoke mortality or clinical signs of
      disease in this fish species, viral production in survivor fish was determined;
      on the other hand the reassortant isolate did cause mortality and clinical signs
      of disease, although less evident than those recorded after RGNNV infection.
      These results suggest that the changes suffered by the SJNNV RNA2 segment of the
      reassortant isolate, compared to the parental SJNNV, may have involved host
      specificity and/or virulence determinants for European sea bass. Regarding
      Senegalese sole, although the three isolates caused 100% mortality, the
      reassortant strain provoked the most acute symptoms, and more quickly, especially
      in the bath challenge. This was also the isolate showing less difference between
      the number of RNA copies and viral titre, reaching the highest titres of
      infective viral particles in nervous tissue of infected animals. The RGNNV
      isolate produced the lowest values of infective viral particles. All these
      results suggest that the RGNNV and the reassortant isolates are the most suited
      for infecting European sea bass and Senegalese sole, respectively. 

PMID- 25770893
TI  - Synovial fluid cytology in experimental acute canine monocytic ehrlichiosis
      (Ehrlichia canis).
AB  - Evidence-based information of a cause-and-effect relationship between Ehrlichia
      canis infection and polyarthritis in naturally- or experimentally-infected dogs
      is currently lacking. The aim of this prospective study was to investigate
      whether synovial fluid cytological evidence of arthritis could be documented in
      dogs with acute monocytic ehrlichiosis. Direct synovial fluid cytology smears
      from eight Beagle dogs experimentally infected with E. canis were examined prior
      to, and on 21, 35 and 63 days post-inoculation. The cytological variables
      assessed included cellularity, percentages of mononuclear cells and neutrophils,
      macrophage reactivity and evidence of E. canis morulae. The median cellularity
      and percentages of mononuclear cells and neutrophils prior to inoculation did not
      differ when compared to post-inoculation cytological evaluation. Increased
      cellularity, E. canis morulae or cytological evidence of arthritis or macrophage
      reactivity were not observed throughout the course of the study. In the present
      study, no cytological evidence of arthritis was found in dogs with experimental
      acute canine monocytic ehrlichiosis, suggesting that E. canis infection should be
      considered a rather uncommon cause of arthritis in dogs. 

PMID- 25770895
TI  - Pathogenic characteristics of Marek's disease virus field strains prevalent in
      China and the effectiveness of existing vaccines against them.
AB  - The virulence of Marek's disease virus (MDV) is continuously evolving, and more
      virulent MDV pathotypes are emerging, thereby reducing the effectiveness of the
      existing vaccines. In this study, feather pulps were collected from diseased
      chickens in commercial chicken flocks in China that presented significant MD
      visceral tumors in 2011 and were inoculated into a monolayer of duck embryo
      fibroblasts (DEFs). Three field isolates of MDV were obtained by plaque cloning
      and identified as MDV via PCR and designated strains LCC, LLY, and LTS.
      Unvaccinated and CVI988 vaccine-vaccinated specific pathogen-free chickens were
      challenged at 7 days post vaccination (dpv) with 1000 plaque forming units of
      each of the respective MDV isolates. These strains induced gross MD lesions in
      all (100%) of the unvaccinated chickens, and the mortality rates of the
      unvaccinated chickens were 42.9%, 46.7%, and 23.1% by 60 days post challenge
      (dpc), respectively. The CVI988 vaccine induced protective indices (PIs) of 85.7,
      92.3, and 66.7, respectively. These results showed that the pathogenic
      characteristics of the Chinese isolates were diverse and that vaccine CVI988
      provided different levels of protection against them. These data indicated that
      the existence of variant MDV strains was a possible reason of immunity failure in
      China. 

PMID- 25770896
TI  - Determination of estrogenic mycotoxins in environmental water samples by low
      toxicity dispersive liquid-liquid microextraction and liquid chromatography
      tandem mass spectrometry.
AB  - A novel, simple, rapid and eco-friendly method based on dispersive liquid-liquid
      microextraction using a bromosolvent was developed to determine six estrogenic
      mycotoxins (zearalenone, zearalanone, alpha-zearalanol, beta-zearalanol, alpha
      zearalenol and beta-zearalenol) in water samples by liquid chromatography
      electrospray ionization tandem mass spectrometry in the negative mode (LC-ESI
      MS/MS). The optimal conditions for this method include the use of 100 MUL
      bromocyclohexane as an extraction solvent (using a non-dispersion solvent), 10 mL
      of aqueous sample (adjusted to pH 4), a vortex extraction time of 2 min,
      centrifugation for 10 min at 3500 rpm and no ionic strength adjustment. The
      calibration function was linear and was verified by applying the Mandel fitting
      test with a 95% confidence level. No matrix effect was observed. According to the
      relative standard deviations (RSDs), the precision was better than 13% for the
      repeatability and intermediate precision. The average recoveries of the spiked
      compounds ranged from 81 to 118%. The method limits of detection (LOD) and
      quantification (LOQ) considering a 125-fold pre-concentration step were 4-20 and
      8-40 ng L(-1), respectively. Next, the method was applied to the analysis of the
      environmental aqueous samples, demonstrating the presence of beta-zearalanol and
      zearalanone in the river water samples.

PMID- 25770894
TI  - Animal models to study the pathogenesis of human and animal Clostridium
      perfringens infections.
AB  - The most common animal models used to study Clostridium perfringens infections in
      humans and animals are reviewed here. The classical C. perfringens-mediated
      histotoxic disease of humans is clostridial myonecrosis or gas gangrene and the
      use of a mouse myonecrosis model coupled with genetic studies has contributed
      greatly to our understanding of disease pathogenesis. Similarly, the use of a
      chicken model has enhanced our understanding of type A-mediated necrotic
      enteritis in poultry and has led to the identification of NetB as the primary
      toxin involved in disease. C. perfringens type A food poisoning is a highly
      prevalent bacterial illness in the USA and elsewhere. Rabbits and mice are the
      species most commonly used to study the action of enterotoxin, the causative
      toxin. Other animal models used to study the effect of this toxin are rats, non
      human primates, sheep and cattle. In rabbits and mice, CPE produces severe
      necrosis of the small intestinal epithelium along with fluid accumulation. C.
      perfringens type D infection has been studied by inoculating epsilon toxin (ETX)
      intravenously into mice, rats, sheep, goats and cattle, and by intraduodenal
      inoculation of whole cultures of this microorganism in mice, sheep, goats and
      cattle. Molecular Koch's postulates have been fulfilled for enterotoxigenic C.
      perfringens type A in rabbits and mice, for C. perfringens type A necrotic
      enteritis and gas gangrene in chickens and mice, respectively, for C. perfringens
      type C in mice, rabbits and goats, and for C. perfringens type D in mice, sheep
      and goats. 

PMID- 25770897
TI  - The management of clenched fist 'fight bite' injuries of the hand.
AB  - We present a prospective study outlining the management of clenched fist 'fight
      bite' injuries. Over a 4-year period all patients with such injuries had surgical
      exploration with further debridements as necessary. For metacarpophalangeal joint
      injuries, a midline tendon-splitting approach was used. For proximal
      interphalangeal joint injuries, an approach was made between the lateral band and
      central slip of the extensor mechanism. A total of 147 patients with 159 joint
      injuries were treated, with 130 metacarpophalangeal joint and 29 proximal
      interphalangeal joint injuries. The joint was penetrated in 96% of joints
      overall. The number of debridements ranged from two to eight. Twenty patients
      defaulted within 1 week of surgery and were not included in the analysis of the
      results. All patients with metacarpophalangeal joint injury had satisfactory or
      good outcomes. A total of 42% of patients with proximal interphalangeal joint
      injuries had poor results, four requiring amputation and one a fusion. The tendon
      splitting approach to the metacarpophalangeal joint allows excellent access and
      avoids damage to the sagittal bands and consequent instability of the extensor
      mechanism. 

PMID- 25770898
TI  - Collagenase induced syndactyly: a case report.

PMID- 25770899
TI  - Scaffolds for hand tissue engineering: the importance of surface topography.
AB  - Tissue engineering is believed to have great potential for the reconstruction of
      the hand after trauma, congenital absence and tumours. Due to the presence of
      multiple distinct tissue types, which together function in a precisely
      orchestrated fashion, the hand counts among the most complex structures to
      regenerate. As yet the achievements have been limited. More recently, the focus
      has shifted towards scaffolds, which provide a three-dimensional framework to
      mimic the natural extracellular environment for specific cell types. In
      particular their surface structures (or topographies) have become a key research
      focus to enhance tissue-specific cell attachment and growth into fully
      functioning units. This article reviews the current understanding in hand tissue
      engineering before focusing on the potential for scaffold topographical features
      on micro- and nanometre scales to achieve better functional regeneration of
      individual and composite tissues. 

PMID- 25770900
TI  - An anatomical study of the superficial palmar communicating branch between the
      median and ulnar nerves.
AB  - The palmar communicating branch between the median and ulnar nerves was
      investigated in 98 hands with the aim of outlining its most common branching
      patterns and describing its relationship to well-defined anatomical landmarks,
      including the bistyloid line, wrist crease and flexor retinaculum. Five branching
      patterns were identified and classified based on their proximal and distal
      attachments. The palmar communicating branch was found to lie between 26%-79% of
      the total distance between the metacarpophalangeal joint of the long finger and
      the wrist crease, and 35%-75% of the total distance between the
      metacarpophalangeal joint of the long finger and the middle of the bistyloid
      line. With the aid of the morphometric indices obtained from this study, a risk
      area where the palmar communicating branch is most likely to be found is
      outlined. Knowledge of the branching patterns and location of the palmar
      communicating branch can help clinicians to better assess variations in the
      patterns of sensation, preserve the nerve during surgical interventions to the
      palm and better assess post-operative complications involving the branch. 

PMID- 25770901
TI  - Pre-operative electrodiagnostic testing predicts time to resolution of symptoms
      after carpal tunnel release.
AB  - The purpose of this study was to determine if nerve conduction studies predict
      time to resolution of symptoms after carpal tunnel release. A total of 56
      patients undergoing open carpal tunnel release were prospectively enrolled. Pre
      operative presence of nocturnal symptoms and daytime numbness/tingling were
      documented. Pre-operative nerve conduction studies were reviewed and classified
      as mild, moderate, or severe. After open carpal tunnel release, patients were
      contacted by phone within 48 hours, at 1 week, and then at 2-week intervals for
      up to 9 months or until both nocturnal and daytime symptoms had resolved. This
      study found that patients with mild or moderate carpal tunnel syndrome experience
      a faster time to resolution of daytime numbness and tingling when compared with
      patients with severe carpal tunnel syndrome. Nocturnal symptoms resolved quickly
      in both groups. The results of this study are in contrast to previous studies
      that found little to no value of nerve conduction studies in predicting post
      operative functional and subjective outcomes. LEVEL OF EVIDENCE: IV.

PMID- 25770902
TI  - The breadth of imaging findings of groove pancreatitis.
AB  - The pathogenesis of groove pancreatitis involves progressive cystic degeneration
      of hamartomatous pancreas rests which lie within the duodenal wall. Hamartomatous
      pancreatic rests can occur in other locations, but when located within the
      pancreaticoduodenal groove can lead to a particular clinical presentation
      following the development of fibrotic and inflammatory tissue. Although this is
      not a disease of the pancreas itself, the pancreatic duct and biliary system is
      frequently secondarily involved in this regional process. Identification of this
      entity and its varied appearances as a distinct pathology is essential given the
      unique management issues of groove pancreatitis. 

PMID- 25770903
TI  - A review of functional pelvic floor imaging modalities and their effectiveness.
AB  - The anatomy of the pelvic floor is complex and clinical examination alone is
      often insufficient to diagnose and assess pathology. With a greater understanding
      of pelvic floor dysfunction and treatment options, imaging is becoming
      increasingly common. This review compares three imaging techniques. Ultrasound
      has the potential for dynamic assessment of the entire pelvic floor. Magnetic
      resonance imaging is able to rapidly image the entire pelvic floor but it is
      expensive and tends to underestimate pathology. Dynamic defaecating proctography
      or cystocolpoproctography is the current gold standard for posterior compartment
      imaging but requires opacification of the bladder to provide a global view. 

PMID- 25770904
TI  - Detection of small brain metastases at 3 T: comparing the diagnostic performances
      of contrast-enhanced T1-weighted SPACE, MPRAGE, and 2D FLASH imaging.
AB  - The aim of this study was to compare the diagnostic performance of contrast
      enhanced T1-weighted sampling perfection with application-optimized contrasts
      using different flip angle evolutions (SPACE), magnetization-prepared rapid
      gradient-echo (MPRAGE), and two-dimensional (2D) fast low angle shot (FLASH) for
      the detection of small brain metastases. Twelve patients who had brain metastases
      less than 10 mm in diameter were enrolled. The diagnostic performance was
      evaluated using alternative free-response receiver operating characteristic
      analysis. Sensitivity and positive predictive value were also calculated. The
      mean Az and sensitivities of SPACE for all observers were significantly higher
      than those of MPRAGE and 2D FLASH. 

PMID- 25770905
TI  - Glomus tumour of the colon: dynamic contrast-enhanced CT findings and review of
      the literature.
AB  - We describe the peculiar enhancement pattern of a subepithelial colonic glomus
      tumour on dynamic contrast-enhanced computed tomography. Discontinuous,
      peripheral nodular enhancement of the colonic lesion followed by subsequent
      centripetal filling-in of contrast was reminiscent of a hepatic haemangioma,
      which has not been described with a glomus or any other subepithelial tumour of
      the colon. When encountered, this tumour enhancement pattern raises the
      possibility of a colonic glomus tumour prior to histological confirmation. 

PMID- 25770906
TI  - Survey on computer aided decision support for diagnosis of celiac disease.
AB  - Celiac disease (CD) is a complex autoimmune disorder in genetically predisposed
      individuals of all age groups triggered by the ingestion of food containing
      gluten. A reliable diagnosis is of high interest in view of embarking on a strict
      gluten-free diet, which is the CD treatment modality of first choice. The gold
      standard for diagnosis of CD is currently based on a histological confirmation of
      serology, using biopsies performed during upper endoscopy. Computer aided
      decision support is an emerging option in medicine and endoscopy in particular.
      Such systems could potentially save costs and manpower while simultaneously
      increasing the safety of the procedure. Research focused on computer-assisted
      systems in the context of automated diagnosis of CD has started in 2008. Since
      then, over 40 publications on the topic have appeared. In this context, data from
      classical flexible endoscopy as well as wireless capsule endoscopy (WCE) and
      confocal laser endomicrosopy (CLE) has been used. In this survey paper, we try to
      give a comprehensive overview of the research focused on computer-assisted
      diagnosis of CD. 

PMID- 25770907
TI  - Investigation of pedestrian crashes on two-way two-lane rural roads in Ethiopia.
AB  - Understanding pedestrian crash causes and contributing factors in developing
      countries is critically important as they account for about 55% of all traffic
      crashes. Not surprisingly, considerable attention in the literature has been paid
      to road traffic crash prediction models and methodologies in developing countries
      of late. Despite this interest, there are significant challenges confronting
      safety managers in developing countries. For example, in spite of the prominence
      of pedestrian crashes occurring on two-way two-lane rural roads, it has proven
      difficult to develop pedestrian crash prediction models due to a lack of both
      traffic and pedestrian exposure data. This general lack of available data has
      further hampered identification of pedestrian crash causes and subsequent
      estimation of pedestrian safety performance functions. The challenges are similar
      across developing nations, where little is known about the relationship between
      pedestrian crashes, traffic flow, and road environment variables on rural two-way
      roads, and where unique predictor variables may be needed to capture the unique
      crash risk circumstances. This paper describes pedestrian crash safety
      performance functions for two-way two-lane rural roads in Ethiopia as a function
      of traffic flow, pedestrian flows, and road geometry characteristics. In
      particular, random parameter negative binomial model was used to investigate
      pedestrian crashes. The models and their interpretations make important
      contributions to road crash analysis and prevention in developing countries. They
      also assist in the identification of the contributing factors to pedestrian
      crashes, with the intent to identify potential design and operational
      improvements. 

PMID- 25770908
TI  - Matrix remodeling by MMPs during wound repair.
AB  - Repair following injury involves a range of processes - such as re
      epithelialization, scar formation, angiogenesis, inflammation, and more - that
      function, often together, to restore tissue architecture. MMPs carry out diverse
      roles in all of these activities. In this article, we discuss how specific MMPs
      act on ECM during two critical repair processes: re-epithelialization and
      resolution of scar tissue. For wound closure, we discuss how two MMPs - MMP1 in
      human epidermis and MMP7 in mucosal epithelia - facilitate re-epithelialization
      by cleaving different ECM or ECM-associated proteins to affect similar
      integrin:matrix adhesion. In scars and fibrotic tissues, we discuss that a
      variety of MMPs carry out a diverse range of activities that can either promote
      or limit ECM deposition. However, few of these MMP-driven activities have been
      demonstrated to be due a direct action on ECM. 

PMID- 25770910
TI  - Insights on ADAMTS proteases and ADAMTS-like proteins from mammalian genetics.
AB  - The mammalian ADAMTS superfamily comprises 19 secreted metalloproteinases and 7
      ADAMTS-like proteins, each the product of a distinct gene. Thus far, all appear
      to be relevant to extracellular matrix function or to cell-matrix interactions.
      Most ADAMTS functions first emerged from analysis of spontaneous human and animal
      mutations and genetically engineered animals. The clinical manifestations of
      Mendelian disorders resulting from mutations in ADAMTS2, ADAMTS10, ADAMTS13,
      ADAMTS17, ADAMTSL2 and ADAMTSL4 identified essential roles for each gene, but
      also suggested potential cooperative functions of ADAMTS proteins. These
      observations were extended by analysis of spontaneous animal mutations, such as
      in bovine ADAMTS2, canine ADAMTS10, ADAMTS17 and ADAMTSL2 and mouse ADAMTS20.
      These human and animal disorders are recessive and their manifestations appear to
      result from a loss-of-function mechanism. Genome-wide analyses have determined an
      association of some ADAMTS loci such as ADAMTS9 and ADAMTS7, with specific traits
      and acquired disorders. Analysis of genetically engineered rodent mutations, now
      achieved for over half the superfamily, has provided novel biological insights
      and animal models for the respective human genetic disorders and suggested
      potential candidate genes for related human phenotypes. Engineered mouse mutants
      have been interbred to generate combinatorial mutants, uncovering cooperative
      functions of ADAMTS proteins in morphogenesis. Specific genetic models have
      provided crucial insights on mechanisms of osteoarthritis (OA), a common adult
      onset degenerative condition. Engineered mutants will facilitate interpretation
      of exome variants identified in isolated birth defects and rare genetic
      conditions, as well as in genome-wide screens for trait and disease associations.
      Mammalian forward and reverse genetics, together with genome-wide analysis,
      together constitute a powerful force for revealing the functions of ADAMTS
      proteins in physiological pathways and health disorders. Their continuing use,
      together with genome-editing technology and the ability to generate stem cells
      from mutants, presents numerous opportunities for advancing basic knowledge,
      human disease pathways and therapy. 

PMID- 25770911
TI  - Prevalence of tuberculosis in adolescents, western Kenya: implications for
      control programs.
AB  - OBJECTIVE: The aim of this study was to determine the prevalence of tuberculosis
      (TB) in adolescents in western Kenya. METHODS: A cohort study of 5004 adolescents
      aged 12-18 years was conducted. Adolescents were screened for prevalent TB using
      clinical criteria, history of TB contact, and a Mantoux test. Cases of suspected
      TB were investigated through two sputum examinations (microscopy and liquid
      culture) and chest radiography. RESULTS: Out of 5004 adolescents enrolled, 1960
      (39.2%) were identified with suspected TB, including 1544 with a positive Mantoux
      (prevalence 1544/4808, 32.1%), 515 with symptoms suggestive of TB (10.3%), and
      144 (2.9%) with household TB contact. Sixteen culture-confirmed (definite) and 18
      probable pulmonary TB (PTB) cases were identified, reflecting a prevalence
      estimate of 3.2/1000 (definite) and 6.8/1000 all PTB, respectively. Only one
      smear-positive case was detected. The case notification rate among 12-18-year-old
      adolescents for all TB was 101/100000, yielding a patient diagnostic rate of 0.13
      (95% confidence interval 0.03-3.7) cases detected per person-year for all TB.
      CONCLUSION: The prevalence of PTB among adolescents is high, with the majority of
      cases not detected routinely. Innovative active case finding including the wider
      use of Xpert MTB/RIF is needed to detect smear-negative TB among adolescents.

PMID- 25770912
TI  - Detecting the association between meteorological factors and hand, foot, and
      mouth disease using spatial panel data models.
AB  - OBJECTIVES: The aim of this study was to quantify the relationship between
      meteorological factors and the occurrence of hand, foot, and mouth disease (HFMD)
      among children in Shandong Province, China, at a county level, using spatial
      panel data models. METHODS: Descriptive analysis was applied to describe the
      epidemic characteristics of HFMD from January 2008 to December 2012, and then a
      global autocorrelation statistic (Moran's I) was used to detect the spatial
      autocorrelation of HFMD in each year. Finally, spatial panel data models were
      performed to explore the association between the incidence of HFMD and
      meteorological factors. RESULTS: Moran's I at the county level were high, from
      0.30 to 0.45 (p < 0.001), indicating the existence of a high spatial
      autocorrelation on HFMD. Spatial panel data models are more appropriate to
      describe the data. Results showed that the incidences of HFMD in Shandong
      Province, China were significantly associated with average temperature, relative
      humidity, vapor pressure, and wind speed. CONCLUSIONS: Spatial panel data models
      are useful when longitudinal data with multiple units are available and spatial
      autocorrelation exists. The association found between HFMD and meteorological
      factors makes a contribution towards advancing knowledge with respect to the
      causality of HFMD and has policy implications for HFMD prevention and control.

PMID- 25770913
TI  - Convenience foods, as portrayed by a consumer organisation. Test-Aankoop/Test
      Achats (1960-1995).
AB  - Food choice, both today and in the past, is driven by a broad range of
      interacting factors, in which culture is centrally placed. This paper will assess
      convenience foods by means of a qualitative analysis of comparative product tests
      done by Belgium's largest consumer organisation Test-Aankoop/Test-Achats, and
      will focus on the influence of socially and culturally normative values between
      the years 1960 and 1995. The tests provide a unique insight into attitudes to
      convenience foods within an organisation that saw its role in Belgian consumer
      society as being both educator and guide. The organisation's views on health,
      food safety, modernity, tradition, control over ingredients and content, gender
      roles and taste shaped its attitude to the role and meaning of what food is
      supposed to be. The organisation thereby both guided and re-affirmed normative
      values with respect to convenience foods. Values, which are culturally
      constructed, have always played a key role in the acceptability of products.
      Cultural and social inhibitions and fears over control of convenience foods,
      which persist today, were central in the consumer organisation's representation
      of convenience food. 

PMID- 25770914
TI  - Comparative optimism about healthy eating.
AB  - The present study investigated people's perception of their own as compared to
      their peers' healthy eating and related these perceptions to actual healthy
      eating, BMI, and subsequent healthy eating behavior. Data were collected within
      the framework of the longitudinal cohort study Konstanz Life Study (T1: N = 770;
      T2: N = 510). Our results demonstrated an optimistic bias on the group level.
      Specifically, people rated their own eating behavior as healthier on average than
      that of their average peers. This comparative optimism occurred even when actual
      healthy eating was unfavorable and BMI was high. However, it increased with
      actual healthy eating behavior. Importantly, optimistic perceptions were
      positively related to the intention to eat healthily and healthy eating six
      months later. Hence, the results suggest that an optimistic comparative view of
      one's own healthy eating is grounded in reality and boosts rather than deters
      subsequent health behavior. This implies that there might not be a need to reduce
      optimistic perceptions of healthy eating behavior.

PMID- 25770915
TI  - [Medical abortion provided by telemedicine to women in Latin America:
      complications and their treatment].
AB  - OBJECTIVE: To analyze reported complications and their treatment after a medical
      abortion with mifepristone and misoprostol provided by a telemedicine service to
      women living in Latin America. METHODS: Observational study based on the registry
      of consultations in a telemedicine service. A total of 872 women who used the
      service in 2010 and 2011 participated in the study. The dependent variables were
      overall complications, hemorrhage, incomplete abortion, overall treatments,
      surgical evacuation, and antibiotics. Independent variables were age, area of
      residence, socioeconomic deprivation, previous children, pregnancies and
      abortions, and week of pregnancy. We fitted Poisson regression models with robust
      variance to estimate incidence ratios and 95% confidence intervals (95%CI).
      RESULTS: Complications were reported by 14.6% of the participants: 6.2% reported
      hemorrhage and 6.8% incomplete abortion. Nearly one-fifth (19.0%) received
      postabortion treatment: 10.9% had a surgical evacuation and 9.3% took
      antibiotics. Socioeconomic deprivation increased the risk of complications by 64%
      (95%CI: 15%-132%), and, among these, the risk of incomplete abortion by 82%
      (95%CI: 8%-206%) and the risk of surgical intervention by 62% (95%CI: 7%-144%).
      Previous pregnancies increased the risk of complications and, specifically, the
      risk of hemorrhage by 2.29 times (95%CI: 1.33-3.95%). Women with a pregnancy of
      12 or more weeks had a 2.45 times higher risk of receiving medical treatment and
      a 2.94 times higher risk of taking antibiotics compared with women with
      pregnancies of 7 or less weeks. CONCLUSION: Medical abortion provided by
      telemedicine seems to be a safe and effective alternative in contexts where it is
      legally restricted.

PMID- 25770917
TI  - N-substituted pyrrole-based scaffolds as potential anticancer and antiviral lead
      structures.
AB  - Undoubtedly, efficient cancer treatment has been a significant challenge for the
      scientific community over the last decades. Despite tremendous progress made
      towards this direction, there are still efforts needed to discover new anticancer
      drugs. In this work, a series of N-substituted pyrrolebased scaffolds have been
      synthesized and evaluated for antiproliferative activity against a panel of
      cancer cell lines (L1210, CEM and HeLa). Furthermore, in order to discover new
      scaffolds as antiviral agents, all the examined compounds were evaluated for
      activity against different types of DNA and RNA viruses. The key feature of the
      above structures is the existence of an aromatic ring with at least one hydrogen
      bonding donor and acceptor group. Results have shown noteworthy cytostatic
      activity for three of the synthesized compounds (1, 3 and 9). Especially,
      compound 1, containing a tropolone ring, proved to be the most promising scaffold
      (IC50:10-14 uM) for the development of novel potential anticancer agents. In
      addition, compound 1 has shown modest anti-HSV-1, -HSV2 activity in HEL cell
      cultures (EC50: 27-40 uM). 

PMID- 25770916
TI  - [Excess mortality associated with influenza in Spain in winter 2012].
AB  - OBJECTIVE: An excess of mortality was detected in Spain in February and March
      2012 by the Spanish daily mortality surveillance system and the "European
      monitoring of excess mortality for public health action" program. The objective
      of this article was to determine whether this excess could be attributed to
      influenza in this period. METHODS: Excess mortality from all causes from 2006 to
      2012 were studied using time series in the Spanish daily mortality surveillance
      system, and Poisson regression in the European mortality surveillance system, as
      well as the FluMOMO model, which estimates the mortality attributable to
      influenza. Excess mortality due to influenza and pneumonia attributable to
      influenza were studied by a modification of the Serfling model. To detect the
      periods of excess, we compared observed and expected mortality. RESULTS: In
      February and March 2012, both the Spanish daily mortality surveillance system and
      the European mortality surveillance system detected a mortality excess of 8,110
      and 10,872 deaths (mortality ratio (MR): 1.22 (95% CI:1.21-1.23) and 1.32 (95%
      CI: 1.29-1.31), respectively). In the 2011-12 season, the FluMOMO model
      identified the maximum percentage (97%) of deaths attributable to influenza in
      people older than 64 years with respect to the mortality total associated with
      influenza (13,822 deaths). The rate of excess mortality due to influenza and
      pneumonia and respiratory causes in people older than 64 years, obtained by the
      Serfling model, also reached a peak in the 2011-2012 season: 18.07 and 77.20,
      deaths per 100,000 inhabitants, respectively. CONCLUSION: A significant increase
      in mortality in elderly people in Spain was detected by the Spanish daily
      mortality surveillance system and by the European mortality surveillance system
      in the winter of 2012, coinciding with a late influenza season, with a
      predominance of the A(H3N2) virus, and a cold wave in Spain. This study suggests
      that influenza could have been one of the main factors contributing to the
      mortality excess observed in the winter of 2012 in Spain.

PMID- 25770918
TI  - The palpebral conjunctival epithelium thickness in young adults measured by
      optical coherence tomography.
AB  - OBJECTIVE: To measure the palpebral conjunctival epithelium thickness in young
      adults with optical coherence tomography (OCT). METHODS: A Cirrus HD-OCT 4000
      system was used to image the superior palpebral conjunctival with the Anterior
      Segment 5 Line Raster scanning protocol at the central region in 36 male and 26
      female subjects aged between 20 and 30 years of age with normal, healthy eyes.
      The palpebral conjunctival epithelium thickness was measured according to the
      difference in brightness on OCT between the epithelium and its underlying
      substantia propria. The measurements were respectively performed in the same
      subjects by two operators and the Bland-Altman plot and intraclass correlation
      coefficient (ICC) were used to measure the agreement between two operators.
      RESULTS: No difference in the palpebral conjunctival epithelium thickness was
      found between the males (34.00+/-5.78 MUm) and females (33.67+/-4.51 MUm)
      (t=0.2425, p=0.8095). The mean values of the superior palpebral conjunctival
      epithelium thickness from operator 1 and operator 2 were 33.81+/-5.04 MUm and
      34.74+/-4.28 MUm, respectively. The analysis of inter-operator variability
      demonstrated a good agreement between two operators: ICC=0.944, F=17.787,
      p<0.001; on the Bland-Altman plot, the 95% limits included 100% of differences
      between the two operators and the maximal difference is 5 MUm. CONCLUSION: The
      palpebral conjunctival epithelium thickness can be measured using OCT with a good
      repeatability.

PMID- 25770919
TI  - Populations potentially exposed to traffic-related air pollution in seven world
      cities.
AB  - Traffic-related air pollution (TRAP) likely exerts a large burden of disease
      globally, and in many places, traffic is increasing dramatically. The impact,
      however, of urban form on the portion of population potentially exposed to TRAP
      remains poorly understood. In this study, we estimate portions of population
      potentially exposed to TRAP across seven global cities of various urban forms.
      Data on population distributions and road networks were collected from the best
      available sources in each city and from remote sensing analysis. Using spatial
      mapping techniques, we first overlaid road buffers onto population data to
      estimate the portions of population potentially exposed for four plausible impact
      zones. Based on a most likely scenario with impacts from highways up to 300meters
      and major roadways up to 50meters, we identified that the portions of population
      potentially exposed for the seven cities ranged from 23 to 96%. High-income North
      American cities had the lowest potential exposure portions, while those in Europe
      had the highest. Second, we adjusted exposure zone concentration levels based on
      a literature suggested multiplier for each city using corresponding background
      concentrations. Though Beijing and Mexico City did not have the highest portion
      of population exposure, those in their exposure zones had the highest levels of
      exposure. For all seven cities, the portion of population potentially exposed was
      positively correlated with roadway density and, to a lesser extent, with
      population density. These analyses suggest that urban form may influence the
      portion of population exposed to TRAP and vehicle emissions and other factors may
      influence the exposure levels. Greater understanding of urban form and other
      factors influencing potential exposure to TRAP may help inform interventions that
      protect public health.

PMID- 25770920
TI  - A normal life without muscle dystrophin.
AB  - Here we summarize the clinical history of Ringo, a golden retriever muscular
      dystrophy (GRMD) dog, who had a mild phenotype despite the absence of muscle
      dystrophin. Ringo died of cardiac arrest at age 11 and therefore displayed a
      normal lifespan. One of his descendants, Suflair, born April 2006, also displays
      a mild course. Dystrophin analysis confirmed total absence of muscle dystrophin
      in both dogs. Muscle utrophin expression did not differ from severely affected
      GRMD dogs. Finding what protects these special dogs from the dystrophic
      degeneration process is now a great challenge that may open new avenues for
      treatment. But most importantly, the demonstration that it is possible to have a
      functional muscle, in a medium-large animal even in the absence of dystrophin,
      brings new hope for Duchenne patients. 

PMID- 25770921
TI  - The hippocampus: A central node in a large-scale brain network for memory.
AB  - The medial temporal lobe is a key region in the formation and consolidation of
      conscious or declarative memories. In this review, we will first consider the
      role of the hippocampus and its surrounding medial temporal lobe structures in
      recognition memory from a historical perspective. According to the dual process
      model of recognition memory, recognition judgments can be based on the
      recollection of details about previous presented stimuli or on the feeling of
      familiarity. Studies in humans, primates and rodents suggest that the
      hippocampus, the parahippocampal cortex and the perirhinal cortex play different
      roles in recollection and familiarity. Then, we will describe the role of the
      hippocampus and neocortex in memory consolidation: a process in which novel
      memories become integrated into long-term memory. After presenting possible
      mechanisms underlying sleep-dependent declarative memory consolidation, we will
      discuss the phenomenon of accelerated long-term forgetting. This type of memory
      deficit is often observed in epileptic patients with a hippocampal lesion, and
      provides a novel opportunity to investigate post-encoding and memory
      consolidation processes. 

PMID- 25770922
TI  - Health-care workers as agents of sustainable development.

PMID- 25770924
TI  - Macrophages and cancer: from mechanisms to therapeutic implications.
AB  - Infiltration by immune cells is a hallmark of most forms of malignancy. In this
      context, tumor-associated macrophages (TAMs) represent key regulators of the
      complex interplay between the immune system and cancer. We discuss evidence
      indicating that in many settings TAMs fuel, rather than limit, tumor progression,
      and negatively impact on responses to therapy. We discuss how the unique
      functional properties of TAMs are shaped by tumor-derived signals, placing TAM
      development in the context of the broader understanding of the cellular and
      molecular mechanisms controlling macrophage origin, differentiation, and
      maintenance in tissues. Finally, we provide examples of how a molecular
      understanding of the relationships between TAMs and the tumor microenvironment
      may lead to improved cancer therapies. 

PMID- 25770923
TI  - Intertwined regulation of angiogenesis and immunity by myeloid cells.
AB  - Angiogenesis is a hallmark of cancer because its induction is indispensable to
      fuel an expanding tumor. The tumor microenvironment contributes to tumor vessel
      growth, and distinct myeloid cells recruited by the tumor have been shown not
      only to support angiogenesis but also to foster an immune suppressive environment
      that supports tumor expansion and progression. Recent findings suggest that the
      intertwined regulation of angiogenesis and immune modulation can offer
      therapeutic opportunities for the treatment of cancer. We review the mechanisms
      by which distinct myeloid cell populations contribute to tumor angiogenesis,
      discuss current approaches in the clinic that are targeting both angiogenic and
      immune suppressive pathways, and highlight important areas of future research. 

PMID- 25770925
TI  - Comparative study of membranes induced by PMMA or silicone in rats, and influence
      of external radiotherapy.
AB  - The induced membrane technique has been used for long bone defect reconstruction
      after traumatism. One of the major drawbacks of this method is the difficult
      removal of the polymethyl methacrylate spacer after membrane formation. We
      therefore replaced the stiff PMMA spacer with a semi-flexible medical grade
      silicone spacer. This study aimed to compare subcutaneously formed membranes,
      induced by PMMA and silicone, in the irradiated or not irradiated areas within 28
      rats that received the spacers. Histological analysis was performed to evaluate
      the composition of the membrane and to quantify the amount of vessels.
      Histomorphometric measurements were used to evaluate membranes' thickness, while
      fibrosis and inflammation were scored. The expression of VEGF and BMP-2 in
      lysates of the crushed membranes was determined by Western blotting. ALP
      expression was analyzed in HBMSC cultures in contact with the same lysates. Non
      irradiated membranes induced by the two spacer types were non-inflammatory,
      fibrous and organized in layers. Irradiation did not change the macroscopic
      properties of membranes that were induced by silicone, while PMMA induced
      membranes were sensitive to the radiotherapy, resulting in thicker, strongly
      inflammatory membranes. Irradiated membranes showed an overall reduced osteogenic
      potential. Medical grade silicone is safe for the use in radiotherapy and might
      therefore be of great advantage for patients in need of cancer treatment. 

PMID- 25770926
TI  - Advancing the delivery of anticancer drugs: Conjugated polymer/triterpenoid
      composite.
AB  - Exemplifying the synergy of anticancer properties of triterpenoids and ion
      retention qualities of conjugated polymers, we propose a conducting matrix to be
      a reservoir of anticancer compounds. In this study, poly(3,4
      ethylenedioxythiophene), PEDOT, based matrix for electrically triggered and local
      delivery of the ionic form of anticancer drug, oleanolic acid (HOL), has been
      investigated. An initial, one-step fabrication procedure has been proposed,
      providing layers exhibiting good drug release properties and biological activity.
      Investigation of obtained systems and implementation of modifications revealed
      another route of fabrication. This procedure was found to yield layers possessing
      a significantly greater storage capacity of OL(-), as evidenced by the 52%
      increase in the drug concentrations attainable through electro-assisted release.
      Examination of the biological activity of immobilised and released OL(-)
      molecules proved that electrochemical treatment has negligible impact on the
      anticancer properties of OL(-), particularly when employing the three-step
      procedure, in which the range of applied potentials is limited. PEDOT/OL(-)
      composite has been demonstrated to be a robust and cost-effective material for
      controlled drug delivery. 

PMID- 25770927
TI  - Zebrafish: A possible tool to evaluate bioactive ions.
AB  - Zebrafish is a well-established model organism with a skeletal structure that
      highly resembles mammalian bone. Yet its use in the research field of
      biomaterials has been limited. One area that could benefit from this model system
      is the evaluation of ionic dissolution products from different materials. As a
      proof of concept we have evaluated the effect of silicate ions on the zebrafish
      larvae and compared it to a well-known osteoblastic cell line, MC3T3-E1 subclone
      14. We have shown that sodium metasilicate (125 MUM and 625 MUM) induces more
      mineralisation in a dose-dependent manner in zebrafish larvae, 9 days post
      fertilisation as compared to the non-treated group. Moreover the same trends were
      seen when adding sodium metasilicate to MC3T3-E1 cultures, with more
      mineralisation and higher ALP levels with higher doses of silicate (25, 125 and
      625 MUM). These results indicate the feasibility of zebrafish larvae for ionic
      dissolution studies. The zebrafish model is superior to isolated cell cultures in
      the aspect that it includes the whole bone remodelling system, with osteoblasts,
      osteoclasts and osteocytes. Zebrafish could thus provide a powerful in vivo tool
      and be a bridge between cell culture systems and mammalian models.

PMID- 25770928
TI  - Effect of ion release from Cu-doped 45S5 Bioglass(r) on 3D endothelial cell
      morphogenesis.
AB  - Both silicate-based bioactive glasses and copper ions have demonstrated
      angiogenic activity and therefore represent promising bioinorganic agents for the
      promotion of vascularization in tissue-engineered scaffolds. This study examined
      the effect of ionic release products from 45S5 Bioglass(r) doped with 0 and 2.5
      wt.% CuO (BG and Cu-BG respectively) on the formation of capillary-like networks
      by SVEC4-10 endothelial cells (ECs) seeded in a three-dimensional (3D) type I
      collagen matrix. Copper and silicon release following 24h dissolution increased
      non-proportionally with Cu-BG concentration in cell culture medium, while calcium
      levels were decreased below the initial medium concentration. EC network length,
      connectivity, branching, quantified by means of a 3D morphometric image analysis
      method, as well as proliferation and metabolic activity were reduced in a dose
      dependent fashion by BG and Cu-BG ionic release products. This reduction was less
      prominent for BG compared to an equivalent concentration of Cu-BG, which was
      attributed to a lower extent of silicon release and calcium consumption.
      Moreover, a CuCl2 dose equivalent to the highest concentration of Cu-BG exhibited
      no effect on ECs. In conclusion, while the previously reported pro-angiogenic
      activity of both Bioglass(r) and copper may not be reflected in a direct response
      of ECs, this study provides a maximum glass concentration for non-harmful
      angiogenic stimulation to be examined in future work.

PMID- 25770929
TI  - Nordihydroguiaretic acid attenuates skin tumorigenesis in Swiss albino mice with
      the condition of topical co-administration of an immunosuppressant.
AB  - Drug and chemically-induced immunosuppression has been implicated as a
      confounding factor for cancer development. Management of cancer in such situation
      is often a challenging task. We tested the efficacy of nordihydroguiaretic acid
      (NDGA) against immunosuppressant tacrolimus-induced augmentation of mouse skin
      tumorigenesis. It was observed that topical administration of tacrolimus
      significantly accelerated the tumor promotion events in dimethylbenz(a)anthracene
      (DMBA)-initiated and 12-O-tetradecanoylphorbol-13-acetate (TPA) promoted two
      stage mouse skin carcinogenesis, which were accompanied by reduced CD4(+)/CD8(+)
      ratio of lymph nodes and serum IL-2 level. NDGA pre-treatment before each TPA
      application reduced the tumor incidence, its multiplicity and volume together
      with improvement in histopathological alterations and decrease in proliferating
      cell nuclear antigen (PCNA) labeling index (LI). However, NDGA had no significant
      influence on the immunosuppressive effect of tacrolimus. The present study
      demonstrates chemopreventive effect of NDGA in normal as well as in the condition
      of immunosuppression. Thus, NDGA has the potential to inhibit or delay the onset
      of tumor development during immunosuppressive regimen. 

PMID- 25770930
TI  - Combination of chrysin and cisplatin promotes the apoptosis of Hep G2 cells by up
      regulating p53.
AB  - Cisplatin is a chemotherapy drug commonly used for the treatment of human
      cancers, however, drug resistance poses a major challenge to clinical application
      of cisplatin in cancer therapy. Recent studies have shown that chrysin, a natural
      flavonoid widely found in various plants and foods, demonstrated effective anti
      cancer activity. In the present study, we found that the combination chrysin and
      cisplatin significantly enhanced the apoptosis of Hep G2 cancer cells.
      Combination of chrysin and cisplatin increased the phosphorylation and
      accumulation of p53 through activating ERK1/2 in Hep G2 cells, which led to the
      overexpression of the pro-apoptotic proteins Bax and DR5 and the inhibition of
      the anti-apoptotic protein Bcl-2. In addition, combination of chrysin and
      cisplatin promoted both extrinsic apoptosis by activating caspase-8 and intrinsic
      apoptosis by increasing the release of cytochrome c and activating caspase-9 in
      Hep G2 cells. Our results suggest that combination of chrysin and cisplatin is a
      promising strategy for chemotherapy of human cancers that are resistant to
      cisplatin. 

PMID- 25770931
TI  - Evaluation of the toxic potential of cefotaxime in the third instar larvae of
      transgenic Drosophila melanogaster.
AB  - The present study was carried out to evaluate the toxic potential of cefotaxime
      in the third instar larvae of transgenic Drosophila melanogaster (hsp70
      lacZ)Bg(9). Cefotaxime at final concentration of 10, 20, 40, 60 and 80 MUg/ml was
      mixed in the diet and the larvae were exposed to the selected doses for 6, 12,
      24, 48 h. The hsp70 expression, trypan blue exclusion test, in situ histochemical
      beta-galactosidase activity, lipid peroxidation, total protein content,
      glutathione (GSH) content, glutathione-S-transferase (GST) activity, protein
      carbonyl content, caspase 3 and 9 activity, apoptotic index and comet assay were
      taken as parameters for the study. The larvae exposed to 40, 60 and 80 MUg/ml for
      12, 24 and 48 h showed a dose and duration dependent significant increase in the
      activity of beta-galactosidase and lipid peroxidation but decrease in the total
      GSH content as compared to unexposed larvae. The decrease in protein content was
      observed in the larvae exposed to 40, 60 and 80 MUg/ml of cefotaxime for 24 and
      48 h. The larvae exposed to 40, 60 and 80 MUg/ml of cefotaxime for 24 and 48 h
      showed a dose and duration dependent increase in the tissue damage, GST, caspase
      3 and 9 activity, PC content, apoptosis and the DNA tail length (comet assay).
      The result suggests that the cefotaxime is toxic at 40, 60 and 80 MUg/ml of doses
      for the third instar larvae of transgenic D. melanogaster (hsp70-lacZ)Bg(9).
      Cefotaxime at 10 and 20 MUg/ml was not toxic for any duration of exposure.

PMID- 25770932
TI  - Mitochondria and redox homoeostasis as chemotherapeutic targets of Araucaria
      angustifolia (Bert.) O. Kuntze in human larynx HEp-2 cancer cells.
AB  - Natural products are among one of the most promising fields in finding new
      molecular targets in cancer therapy. Laryngeal carcinoma is one of the most
      common cancers affecting the head and neck regions, and is associated with high
      morbidity rate if left untreated. The aim of this study was to examine the
      antiproliferative effect of Araucaria angustifolia on laryngeal carcinoma HEp-2
      cells. The results showed that A. angustifolia extract (AAE) induced a
      significant cytotoxicity in HEp-2 cells compared to the non-tumor human
      epithelial (HEK-293) cells, indicating a selective activity of AAE for the cancer
      cells. A. angustifolia extract was able to increase oxidative damage to lipids
      and proteins, and the production of nitric oxide, along with the depletion of
      enzymatic antioxidant defenses (superoxide dismutase and catalase) in the tumor
      cell line. Moreover, AAE was able to induce DNA damage, nuclear fragmentation and
      chromatin condensation. A significant increase in the Apoptosis Inducing Factor
      (AIF), Bax, poly-(ADP-ribose) polymerase (PARP) and caspase-3 cleavage expression
      were also found. These effects could be related to the ability of AAE to increase
      the production of reactive oxygen species through inhibition of the mitochondrial
      electron transport chain complex I activity and ATP production by the tumor
      cells. The phytochemical analysis of A. angustifolia, performed using High
      Resolution Mass Spectrometry (HRMS) in MS and MS/MS mode, showed the presence of
      dodecanoic and hexadecanoic acids, and phenolic compounds, which may be
      associated with the chemotherapeutic effect observed in this study. 

PMID- 25770933
TI  - Interaction of sugar stabilized silver nanoparticles with the T-antigen specific
      lectin, jacalin from Artocarpus integrifolia.
AB  - The advances in nanomedicine demonstrate the anticancer properties of silver
      nanoparticles (AgNPs) and considered as an alternative to the available
      chemotherapeutic agents. Owing to the preferential interaction of Artocarpus
      integrifolia lectin (jacalin) with Galbeta1-3GalNAcalpha (a chemically well
      defined tumor associated antigen), a study was undertaken to understand the
      interaction mechanism of AgNPs with jacalin in presence of specific sugar,
      galactose. Fluorescence spectroscopic analysis revealed that the AgNPs binding
      significantly quenched the intrinsic fluorescence of jacalin through a static
      quenching mechanism, and a non-radiative energy transfer occurred within the
      molecules. Association constants obtained from the interaction of different sugar
      stabilized AgNPs with jacalin are in the order of 10(4)M(-1), this is in the same
      range as those obtained for the interaction of lectin with carbohydrate and
      hydrophobic ligand. Each subunit of the tetrameric jacalin binds one AgNPs, and
      the stoichiometry was unaffected by the presence of the specific sugar,
      galactose. Hemagglutination assay shows that sugar stabilized AgNPs interacts to
      jacalin at a site that is different from the saccharide-binding site. Analysis of
      the FTIR spectra of jacalin indicates that the binding of AgNPs does not alter
      the secondary structure of jacalin. More importantly, AgNPs exists in nano form
      even after interacting with the lectin. These results suggest that the
      development of lectin-AgNPs conjugate would be possible for diagnosis and
      treatment of cancer. 

PMID- 25770934
TI  - Bioinspired reduced graphene oxide nanosheets using Terminalia chebula seeds
      extract.
AB  - A green one step facile synthesis of graphene nanosheets by Terminalia chebula
      (T. chebula) extract mediated reduction of graphite oxide (GO) is reported in
      this work. This method avoids the use of harmful toxic reducing agents. The
      comparative results of various characterizations of GO and T. chebula reduced
      graphene oxide (TCG) provide a strong indication of the exclusion of oxygen
      containing groups from graphene oxide and successive stabilization of the formed
      reduced graphene oxide (RGO). The functionalization of reduced graphene oxide
      with the oxidized polyphenols causes their stability by preventing the
      aggregation. We also have proposed how the oxidized polyphenols are accountable
      for the stabilization of the formed graphene sheets. 

PMID- 25770935
TI  - Investigation into photostability of soybean oils by thermal lens spectroscopy.
AB  - Assessment of photochemical stability is essential for evaluating quality and the
      shelf life of vegetable oils, which are very important aspects of marketing and
      human health. Most of conventional methods used to investigate oxidative
      stability requires long time experimental procedures with high consumption of
      chemical inputs for the preparation or extraction of sample compounds. In this
      work we propose a time-resolved thermal lens method to analyze photostability of
      edible oils by quantitative measurement of photoreaction cross-section. An all
      numerical routine is employed to solve a complex theoretical problem involving
      photochemical reaction, thermal lens effect, and mass diffusion during local
      laser excitation. The photostability of pure oil and oils with natural and
      synthetic antioxidants is investigated. The thermal lens results are compared
      with those obtained by conventional methods, and a complete set of physical
      properties of the samples is presented. 

PMID- 25770936
TI  - Laccase immobilization on the electrode surface to design a biosensor for the
      detection of phenolic compound such as catechol.
AB  - Biosensors based on the coupling of a biological entity with a suitable
      transducer offer an effective route to detect phenolic compounds. Phenol and
      phenolic compounds are among the most toxic environmental pollutants. Laccases
      are multi-copper oxidases that can oxide phenol and phenolic compounds. A method
      is described for construction of an electrochemical biosensor to detect phenolic
      compounds based on covalent immobilization of laccase (Lac) onto polyaniline
      (PANI) electrodeposited onto a glassy carbon (GC) electrode via glutaraldehyde
      coupling. The modified electrode was characterized by voltammetry, Fourier
      transform infrared (FTIR) spectroscopy and atomic force microscopy (AFM)
      techniques. The results indicated that laccase was immobilized onto modified GC
      electrode by the covalent interaction between laccase and terminal functional
      groups of the glutaraldehyde. The laccase immobilized modified electrode showed a
      direct electron transfer reaction between laccase and the electrode. Linear
      range, sensitivity, and detection limit for this biosensor were 3.2 * 10(-6) to
      19.6 * 10(-6)M, 706.7 mAL mol(-1), 2.07 * 10(-6)M, respectively.

PMID- 25770937
TI  - Structural, conformational and vibrational properties of 1,1,1-Trifluoro-N
      (1,1,2,2,2-pentafluoroethyl) methanesulfinimidoyl chloride, CF3CF2-N=S(Cl)CF3.
AB  - The structural, conformational, and configurational properties of 1,1,1-Trifluoro
      N-(1,1,2,2,2-pentafluoroethyl) methanesulfinimidoyl chloride, CF3CF2NS(Cl)CF3
      have been studied by vibrational spectroscopy [IR (vapor) and Raman (liquid)] and
      quantum chemical calculations [B3LYP, MP2 and B3PW91 levels of theory using the 6
      311+G(d), 6-311+G(df) and 6-311+G(2df) basis sets]. According to these
      theoretical approximations, CF3CF2-N=S(Cl)CF3 exists in the gas phase as a
      mixture of a favored anticlinal form (CN bond anticlinal with respect to the CSCl
      bisector) with C1 symmetry and a less abundant syn conformer showing C1 symmetry
      as well (DeltaG degrees  ~ 1.20 kcal mol(-1)). Due to the small contribution only
      a few corresponding vibrational modes of the syn conformer could be assigned
      confidently in the experimental spectra. Compared to CF3CF2-N=S(F)CF3, the
      replacement of F by Cl produces a clear change in NS bond length and the
      corresponding stretching frequency, without affecting the conformational
      properties.

PMID- 25770938
TI  - Microstructure and optical dispersion characterization of nanocomposite sol-gel
      TiO2-SiO2 thin films with different compositions.
AB  - Nanocomposite TiO2-SiO2 thin films with different compositions (from 0 to 100
      mol% TiO2) were deposited by sol-gel dip-coating method on silicon substrate.
      Crystal structure, chemical bonding configuration, composition and morphology
      evolutions with composition were followed by Raman scattering, Fourier transform
      infrared spectroscopy, energy-dispersive X-ray spectroscopy and scanning electron
      microscopy respectively. The refractive index and the extinction coefficient were
      derived in a broad band wavelength (250-900 nm) from spectroscopic ellipsometry
      data with high accuracy and correlated with composition and microstructure.
      Results showed an anatase structure for 100% TiO2 with a grain size in 6-10nm
      range. Whereas, the inclusion of SiO2 enlarges the optical band gap and
      suppresses the grain growth up to 4 nm in size. High TiO2 dispersion in SiO2
      matrix was observed for all mixed materials. The refractive index (at lambda=600
      nm) increases linearly with composition from 1.48 (in 100% SiO2) to 2.22 (in 100%
      TiO2) leading to lower dense material, its dispersion being discussed in terms of
      the Wemple-DiDomenico single oscillator model. Hence, the optical parameters,
      such optical dispersion energies E0 and Ed, the average oscillators, strength S0
      and wavelength lambda0 and the ratio of the carrier concentration to the
      effective mass N/m(*) have been derived. The analysis revealed a strong
      dependence on composition and structure. The optical response was also
      investigated in term of complex optical conductivity (sigma) and both volume and
      surface energy loss functions (VELF and SELF).

PMID- 25770939
TI  - Endobronchial chondroma: An unusual case of bronchial obstruction.

PMID- 25770940
TI  - Locomotor activity measures in the diagnosis of attention deficit hyperactivity
      disorder: Meta-analyses and new findings.
AB  - INTRODUCTION: Our aim was to assess differences in movement measures in attention
      deficit/hyperactivity disorder (ADHD) vs. typically developing (TD) controls.
      METHODS: We performed meta-analyses of published studies on motion measures
      contrasting ADHD with controls. We also conducted a case-control study with
      children/adolescents (n = 61 TD, n = 62 ADHD) and adults (n = 30 TD, n = 19 ADHD)
      using the McLean motion activity test, semi-structured diagnostic interviews and
      the behavior rating inventory of executive function and Conners (parent, teacher;
      self) rating scales. RESULTS: Meta-analyses revealed medium-to-large effect sizes
      for actigraph (standardized mean difference [SMD]: 0.64, 95% confidence interval
      (CI): 0.43, 0.85) and motion tracking systems (SDM: 0.92, 95% CI: 0.65, 1.20)
      measures in differentiating individuals with ADHD from controls. Effects sizes
      were similar in studies of children/adolescents ([SMD]: 0.75, 95% CI: 0.50, 1.01)
      and of adults ([SMD]: 0.73, 95% CI: 0.46, 1.00). In our sample, ADHD groups
      differed significantly in number of head movements (p = 0.02 in children; p =
      0.002 in adults), displacement (p = 0.009/p < 0.001), head area (p = 0.03/p <
      0.001), spatial complexity (p = 0.06/p = 0.02) and temporal scaling (p = 0.05/p =
      0.04). Mean effect sizes were non-significantly larger (d = 0.83, 95% CI: 0.20,
      1.45) in adults vs. children/adolescents with ADHD (d = 0.45, 95% CI: 0.08,
      0.82). In the concurrent go/no-go task, reaction time variability was
      significantly greater in ADHD (p < 0.05 in both age groups) than controls.
      CONCLUSIONS: Locomotor hyperactivity remains core to the construct of ADHD even
      in adults. Our results suggest that objective locomotion measures may be
      particularly useful in evaluating adults with possible ADHD.

PMID- 25770941
TI  - Miniscrews for orthodontic anchorage: nanoscale chemical surface analyses.
AB  - OBJECTIVES: The goal of this study was to determine the chemical composition of
      the passivation layer of three clinically available orthodontic miniscrews at
      different depths. MATERIALS AND METHODS: The miniscrews used were Aarhus Mini
      Implant (AAR), IMTEC Ortho (IMT), and VectorTAS (VEC). The chemical compositions
      of the as-received miniscrews were determined by X-ray photoelectron spectroscopy
      (XPS). Data was acquired before etching the miniscrews with argon, as well as
      after etching at depths of 10 nm, 20 nm, 30 nm, and 80 nm. RESULTS: The elements
      found in all miniscrews were mainly C, O, and Ti. Also found were other metals in
      small amounts, and other trace elements. All three miniscrews showed very
      different characteristics in surface composition. IMT had the greatest increase
      in Ti, as well as the most titanium metal at 80 nm. VEC remained stable at all
      tested depths and contained no titanium metal at 80 nm. AAR was an intermediate
      between the two. CONCLUSIONS: The passivation layer of the orthodontic miniscrews
      has different compositions depending on the brand, as well as the depth analyzed.
      VEC appeared to have the largest passivation layer, and IMT appeared to have the
      thinnest passivation layer.

PMID- 25770942
TI  - Comparisons of two protocols for the early treatment of Class III dentoskeletal
      disharmony.
AB  - OBJECTIVE: To assess the short-term outcomes of splints, Class III elastics, and
      chincup (SEC III) and rapid maxillary expansion and facial mask (RME/FM)
      protocols. MATERIALS AND METHODS: 25 patients with Class III dentoskeletal
      disharmony (10 males, 15 females) treated with the SEC III protocol were
      evaluated at the beginning (T1, mean age 7.5+/-1.4 years) and at the end of
      treatment (T2, mean age 8.7+/-1.4 years). The SEC III group was compared to a
      matched sample of 32 Class III patients (16 males, 16 females) treated with the
      RME/FM protocol and to a matched control group (CG) consisting of 23 subjects (12
      males, 11 females) with untreated Class III dentoskeletal disharmony. The
      statistical comparisons between the three groups were performed with analysis of
      variance with Tukey's post hoc tests. RESULTS: With respect to the CG the SEC III
      and the RME/FM groups showed significantly favourable effects in terms of
      maxillary advancement (SNA +1.2 and +1.4 degrees, respectively), control of
      mandibular projection (SNB -1.3 and -1.4 degrees, respectively), and
      intermaxillary relationships (ANB +2.6 and +2.9 degrees, respectively; WITS +3.7
      and +2.6mm, respectively). The RME/FM group showed a significantly greater
      increase in the intermaxillary divergency than the SEC III group (+1.8 degrees)
      and the CG (+2.0 degrees). LIMITATIONS: A limitation of this study is its short
      term nature. CONCLUSIONS: Both SEC III and RME/FM protocols are efficient
      treatments for Class III dentoskeletal disharmony. The SEC III protocol produces
      more favourable control in intermaxillary vertical relationships than the RME/FM
      therapy.

PMID- 25770943
TI  - Zinc solubility and fractionation in cultivated calcareous soils irrigated with
      wastewater.
AB  - The solubility, lability and fractionation of zinc in a range of calcareous soils
      from Peshawar, Pakistan were studied (18 topsoils and 18 subsoils). The lability
      (E-value) of Zn was assessed as the fraction isotopically exchangeable with
      (70)Zn(2+); comparative extractions included 0.005 M DTPA, 0.43 M HNO3 and a
      Tessier-style sequential extraction procedure (SEP). Because of the extremely low
      concentration of labile Zn the E-value was determined in soils suspended in
      0.0001 M Na2-EDTA which provided reliable analytical conditions in which
      approximately 20% of the labile Zn was dissolved. On average, only 2.4% of soil
      Zn was isotopically exchangeable. This corresponded closely to Zn solubilised by
      extraction with 0.005 DTPA and by the carbonate extraction step (F1+F2) of the
      Tessier-style SEP. Crucially, although the majority of the soil CaCO3 was
      dissolved in F2 of the SEP, the DTPA dissolved only a very small proportion of
      the soil CaCO3. This suggests a superficial carbonate-bound form of labile Zn,
      accessible to extraction with DTPA and to isotopic exchange. Zinc solubility from
      soil suspended in 0.01 M Ca(NO3)2 (PCO2 controlled at 0.03) was measured over
      three days. Following solution speciation using WHAM(VII) two simple solubility
      models were parameterised: a pH dependent 'adsorption' model based on the labile
      (isotopically exchangeable) Zn distribution coefficient (Kd) and an apparent
      solubility product (Ks) for ZnCO3. The distribution coefficient showed no pH
      dependence and the solubility model provided the best fit to the free ion
      activity (Zn(2+)) data, although the apparent value of log10 Ks (5.1) was 2.8 log
      units lower than that of the mineral smithsonite (ZnCO3).

PMID- 25770944
TI  - Soil processes and tree growth at shooting ranges in a boreal forest reflect
      contamination history and lead-induced changes in soil food webs.
AB  - The effects of shooting-derived lead (Pb) on the structure and functioning of a
      forest ecosystem, and the recovery of the ecosystem after range abandonment were
      studied at an active shotgun shooting range, an abandoned shooting range where
      shooting ceased 20 years earlier and an uncontaminated control site. Despite
      numerous lead-induced changes in the soil food web, soil processes were only
      weakly related to soil food web composition. However, decomposition of Scots pine
      (Pinus sylvestris) needle litter was retarded at the active shooting range, and
      microbial activity, microbial biomass and the rate of decomposition of Pb
      contaminated grass litter decreased with increasing soil Pb concentrations. Tree
      (P. sylvestris) radial growth was suppressed at the active shooting range right
      after shooting activities started. In contrast, the growth of pines improved at
      the abandoned shooting range after the cessation of shooting, despite reduced
      nitrogen and phosphorus contents of the needles. Higher litter degradation rates
      and lower Pb concentrations in the topmost soil layer at the abandoned shooting
      range suggest gradual recovery after range abandonment. Our findings suggest that
      functions in lead-contaminated coniferous forest ecosystems depend on the
      successional stage of the forest as well as the time since the contamination
      source has been eliminated, which affects, e.g., the vertical distribution of the
      contaminant in the soil. However, despite multiple lead-induced changes
      throughout the ecosystem, the effects were rather weak, indicating high
      resistance of coniferous forest ecosystems to this type of stress.

PMID- 25770945
TI  - Lichen, moss and soil in resolving the occurrence of semi-volatile organic
      compounds on the southeastern Tibetan Plateau, China.
AB  - This study investigated a wide range of semi-volatile organic compounds (SVOCs),
      including 28 persistent organochlorine pesticides (OCPs), 18 polychlorinated
      biphenyls (PCBs), 13 polybrominated diphenyl ethers (PBDEs), and 3
      hexabromocyclododecane (HBCD) congeners in lichen, moss and soil collected from
      the southeastern Tibetan Plateau, China. This allows research provides insight
      into elevation gradient distributions and possible cold trapping effects of SVOCs
      in this high mountain area, and compares lichens and mosses as air passive
      samplers for indicating SVOC occurrences. DDTs, endosulfans, HCHs and
      hexachlorobenzene predominated in all of the samples. Source analysis indicted
      that there were fresh inputs of DDTs and HCHs in the sampling region. Lichens and
      mosses shared commonalities in revealing the profiles and levels of SVOCs based
      on their lipid-content-normalized concentrations. The concentrations of 12 OCPs
      and 14 PCBs in lichens were significantly linearly correlated with altitudes,
      whereas the correlations for mosses and soil with altitudes were insignificant.
      Both a frequency distribution diagram and the Mountain Contamination Potential
      Model indicated that SVOCs with specific values of log KOA (8-11) and log KWA (2
      4) had relative high mountain contamination potential on the Tibetan Plateau. 

PMID- 25770946
TI  - Tillage and crop residue management methods had minor effects on the stock and
      stabilization of topsoil carbon in a 30-year field experiment.
AB  - We studied the effects of tillage and straw management on soil aggregation and
      soil carbon sequestration in a 30-year split-plot experiment on clay soil in
      southern Finland. The experimental plots were under conventional or reduced
      tillage with straw retained, removed or burnt. Wet sieving was done to study
      organic carbon and soil composition divided in four fractions: 1) large
      macroaggregates, 2) small macroaggregates, 3) microaggregates and 4) silt and
      clay. To further estimate the stability of carbon in the soil, coarse particulate
      organic matter, microaggregates and silt and clay were isolated from the
      macroaggregates. Total carbon stock in the topsoil (equivalent to 200 kg m(-2))
      was slightly lower under reduced tillage (5.0 kg m(-2)) than under conventional
      tillage (5.2 kg m(-2)). Reduced tillage changed the soil composition by
      increasing the percentage of macroaggregates and decreasing the percentage of
      microaggregates. There was no evidence of differences in the composition of the
      macroaggregates or carbon content in the macroaggregate-occluded fractions.
      However, due to the higher total amount of macroaggregates in the soil, more
      carbon was bound to the macroaggregate-occluded microaggregates in reduced
      tillage. Compared with plowed soil, the density of deep burrowing earthworms
      (Lumbricus terrestris) was considerably higher under reduced tillage and
      positively associated with the percentage of large macroaggregates. The total
      amount of microbial biomass carbon did not differ between the treatments. Straw
      management did not have discernible effects either on soil aggregation or soil
      carbon stock. We conclude that although reduced tillage can improve clay soil
      structure, generally the chances to increase topsoil carbon sequestration by
      reduced tillage or straw management practices appear limited in cereal
      monoculture systems of the boreal region. This may be related to the already high
      C content of soils, the precipitation level favoring decomposition and aggregate
      turnover in the winter with topsoil frost.

PMID- 25770947
TI  - Reducing psychosocial risks through supervisors' development: a contribution for
      a brief version of the "Stress Management Competency Indicator Tool".
AB  - With the recent changes in the world of work psychosocial risks are increasingly
      prevalent, causing work stress and physical and mental illnesses, which have a
      tremendous impact on public health and social participation. Supervisors'
      behaviour development was proposed as an innovative intervention that can reduce
      psychosocial risks. The "Stress Management Competency Indicator Tool" is one of
      the most important questionnaires that assess managers' preventive behaviour.
      However, its psychometric properties have never been evaluated and the length of
      the questionnaire (66 items) limits its practical applicability. The aim of this
      study was to contribute to the development of the questionnaire by providing
      psychometric evidence on a brief version of the tool focusing on the "Managing
      and Communicating existing and future Work" cluster of behaviours, which has been
      found to be the crucial one in terms of stress prevention. A questionnaire was
      administered to 178 employees of two Italian public organizations (a municipality
      and a hospital), measuring the supervisors' "Managing and Communicating existing
      and future Work" competency, and the affective well-being and work team
      effectiveness. The results showed excellent psychometric properties of the
      supervisors' behaviour scale and confirmed the expected relationships with
      criterion outcomes (affective well-being and team effectiveness). Overall, the
      factorial structure and dimensionality, the construct validity and reliability,
      and the concurrent validity of the tool were strongly supported by this study. We
      concluded that the brief version of the scale is a valid and reliable measure
      that can be easily used in practice and that can contribute to the development of
      research and practice on this topic. 

PMID- 25770948
TI  - Quaternary ammonium compounds (QACs): a review on occurrence, fate and toxicity
      in the environment.
AB  - Quaternary ammonium compounds (QACs) are widely applied in household and
      industrial products. Most uses of QACs can be expected to lead to their release
      to wastewater treatment plants (WWTPs) and then dispersed into various
      environmental compartments through sewage effluent and sludge land application.
      Although QACs are considered to be aerobically biodegradable, the degradation is
      affected by its chemical structures, dissolved oxygen concentration, complexing
      with anionic surfactants, etc. High abundance of QACs has been detected in
      sediment and sludge samples due to its strong sorption and resistance to
      biodegradation under anoxic/anaerobic conditions. QACs are toxic to a lot of
      aquatic organisms including fish, daphnids, algae, rotifer and microorganisms
      employed in wastewater treatment systems. And antibiotic resistance has emerged
      in microorganisms due to excessive use of QACs in household and industrial
      applications. The occurrence of QACs in the environment is correlated with
      anthropogenic activities, such as wastewater discharge from WWTPs or single
      source polluters, and sludge land application. This article also reviews the
      analytical methods for determination of QACs in environmental compartments
      including surface water, wastewater, sewage sludge and sediments. 

PMID- 25770949
TI  - Health risks for the population living in the vicinity of an Integrated Waste
      Management Facility: screening environmental pollutants.
AB  - We performed a screening investigation to assess the human health risks of the
      Integrated Waste Management Facility (IWMF: mechanical-biological treatment (MBT)
      plant plus municipal solid waste incinerator (MSWI); Ecoparc-3) of Barcelona
      (Spain). Air concentrations of pollutants potentially released by the MBT plant
      (VOCs and bioaerosols) and the MSWI (trace elements, PCDD/Fs and PCBs) were
      determined. Trace elements, PCDD/Fs and PCBs were also analyzed in soil samples.
      The concentrations of trace elements and bioaerosols were similar to those
      previously reported in other areas of similar characteristics, while formaldehyde
      was the predominant VOC. Interestingly, PCDD/F concentrations in soil and air
      were the highest ever reported near a MSWI in Catalonia, being maximum
      concentrations 10.8 ng WHO-TEQ/kg and 41.3 fg WHO-TEQ/m(3), respectively. In
      addition, there has not been any reduction in soils, even after the closure of a
      power plant located adjacently. Human health risks of PCDD/F exposure in the
      closest urban nucleus located downwind the MSWI are up to 10-times higher than
      those nearby other MSWIs in Catalonia. Although results must be considered as
      very preliminary, they are a serious warning for local authorities. We strongly
      recommend to conduct additional studies to confirm these findings and, if
      necessary, to implement measures to urgently mitigate the impact of the MSWI on
      the surrounding environment. We must also state the tremendous importance of an
      individual evaluation of MSWIs, rather than generalizing their environmental and
      health risks.

PMID- 25770950
TI  - Rapid screening of phytoremediation effluents by off-line tetramethylammonium
      hydroxide assisted thermochemolysis.
AB  - Tetramethylammonium hydroxide-assisted thermochemolysis performed in an off-line
      mode proved a useful tool in determining organic compounds in the effluent from
      laboratory-scale phytoremediation systems. Studies were performed with artificial
      wastewaters contaminated with xylenols and densely rooted Juncus effuses plants.
      Analytes in these molecular-level based studies included xylenol substrates, an
      array of stable intermediates such as low molecular weight carboxylic acids and
      oxidative coupling products (tetramethyl biphenyldiols, tetramethyl diphenylether
      monools), diagnostic fatty acid biomarkers, as well as lignin-, carbohydrate-,
      and protein-based phenols and carboxylic acids. Lignin-based breakdown products
      belonged to p-hydroxyphenyl- and guaiacyl-units, with lower abundance of syringyl
      units and the dominance of acids over phenols. Monomeric lignin-, protein- and
      carbohydrate-based breakdown products could not be detected in the non-treated
      lyophilized effluent. The formation of diketopiperazines pointed to soluble
      peptides and proteins. The procedure described herein can easily be applied in
      every modern laboratory to characterize underlying processes in phytoremediation.

PMID- 25770951
TI  - Columnar and surface aerosol load over the Iberian Peninsula establishing annual
      cycles, trends, and relationships in five geographical sectors.
AB  - The study of atmospheric aerosol load over the Iberian Peninsula (IP) under a
      climatological perspective is accomplished by means of PM10 and AOD440 nm
      measurements from EMEP and AERONET networks, respectively, in the period 2000
      2013. The PM10 annual cycles in five Iberian sectors show a main maximum in
      summer and a secondary maximum in spring, which is only observed in the southern
      area for the AOD climatology. The characteristics of PM10-AOD annual cycles of
      each geographical sector are explained by the different climatology of the air
      mass origins and their apportioning. The two magnitudes are correlated with a
      factor ranging between 20 and 90 depending on the sector. The temporal evolution
      of the aerosol load has shown a notable decrease in the IP since the 1980s.
      Statistically significant trends are obtained in the Northeastern sector with a
      reduction of 26% (period 1985-2000) for the total suspended particles, which
      continues for the PM10 data with a value of 35% per decade (2001-2013), and also
      in the whole column, 61% per decade in the AOD440 nm (2004-2013).

PMID- 25770952
TI  - Nutrient loadings from urban catchments under climate change scenarios: case
      studies in Stockholm, Sweden.
AB  - Anthropogenic nutrient emissions and associated eutrophication of urban lakes are
      a global problem. Future changes in temperature and precipitation may influence
      nutrient loadings in lake catchments. A coupling method, where the Generalized
      Watershed Loading Functions method was tested in combination with source
      quantification in a Substance Flow Analysis structure, was suggested to
      investigate diffuse nutrient sources and pathways and climate change effects on
      the loadings to streamflow in urban catchments. This method may, with an
      acceptable level of uncertainty, be applied to urban catchments for first-hand
      estimations of nutrient loadings in the projected future and to highlight the
      need for further study and monitoring. Five lake catchments in Stockholm, Sweden
      (Racksta Trask, Judarn, Trekanten, Langsjon and Laduviken) were employed as case
      studies and potential climate change effects were explored by comparing loading
      scenarios in two periods (2000-2009 and 2021-2030). For the selected cases, the
      dominant diffuse sources of nutrients to urban streamflow were found to be
      background atmospheric concentration and vehicular traffic. The major pathways of
      the nitrogen loading were suggested to be from both developed areas and natural
      areas in the control period, while phosphorus was indicated to be largely
      transported through surface runoff from natural areas. Furthermore, for nitrogen,
      a modest redistribution of loadings from surface runoff and stormwater between
      seasons and an increase in the annual loading were suggested for the projected
      future climate scenarios as compared to the control period. The model was, due to
      poor monitoring data availability, only able to set an upper limit to nutrient
      transport by groundwater both in the control period and the future scenarios.
      However, for nitrogen, groundwater appeared to be the pathway most sensitive to
      climate change, with a considerable increase and seasonal redistribution of
      loadings. For phosphorus, loadings by different pathways were apparently less
      sensitive to climate change. 

PMID- 25770953
TI  - Variable contribution of functional prey groups in diets reveals inter- and
      intraspecific differences in faecal concentrations of essential and non-essential
      elements in three sympatric avian aerial insectivores: a re-assessment of
      usefulness of bird faeces in metal biomonitoring.
AB  - Aerial insectivores through their insect diet can contribute to biotransfer of
      elements across habitats. We investigate the relationship between dietary
      composition as expressed by the contributions of six functional invertebrate prey
      groups (primarily of agriculturally subsidised invertebrates characteristic of
      agricultural areas in temperate regions of Europe) and concentrations of
      essential (Na, K, Ca, Mg, Fe, Cu, Zn, Mn, Co) and non-essential (As, Cd, Pb)
      elements of environmental concern in the faeces of nestlings of three species of
      avian aerial insectivores - Common Swift Apus apus, Barn Swallow Hirundo rustica
      and House Martin Delichon urbicum - which breed sympatrically and use apparently
      similar resources of flying insect prey. There were significant differences
      between the species for 7 of the 12 elements (Ca, Zn, Cu, Co, As, Pb, Cd); these
      differences were attributable to the variable dietary composition, even though
      the concentrations of the elements varied enormously between the faecal samples
      from the individual species. Partial correlation analysis between the biomass
      (expressed in mg dry weight) of the six functional prey groups and faecal
      concentrations of elements showed the highest number of significant relationships
      for toxic metals (As, Pb and Cd). The results of the General Regression Model
      explaining faecal element concentrations revealed the different explanatory power
      of the effects of PCA (of six functional prey groups) dietary scores. A
      significant fit of GRM was obtained for 7 elements (Na, Mg, Fe, Mn, As, Pb, Cd)
      for Barn Swallows, 2 elements (Cu, As) for House Martins and 1 element (Mn) for
      Common Swifts. Overall, the results confirmed our predictions that the biomass of
      consumed coprophilous taxa and insects from crop habitats was positively
      correlated with the faecal concentrations of toxic elements. Unexpectedly,
      however, the faecal samples (primarily those of Common Swifts) that contained
      many oil-seed rape insect pests had lower Ca, Pb and Cd levels and a higher As
      level. Our study implies that the cross-boundary transfer of contaminants,
      primarily non-essential elements, by aerially foraging birds through the
      considerable accumulation of their faeces has potential consequences for the
      local biogeochemical cycle and environmental quality. 

PMID- 25770954
TI  - Track of fate and primary metabolism of trifloxystrobin in rice paddy ecosystem.
AB  - Trifloxystrobin, a strobilurin fungicide, has been widely applied to control
      fungal diseases in various crops, especially in rice cultivation. However, its
      residual profile in rice paddy that was highly linked to its ecological risk
      still remains poorly understood. To elucidate the fate and primary metabolism of
      trifloxystrobin in rice paddy, a simple and efficient analytical method was
      developed using the DisQuE extraction kit combined with GC-MUECD and GC-EI-MS/MS
      analyses. As a result, methodological recoveries of trifloxystrobin fortified in
      paddy water, soil and rice straw ranging from 0.005 to 2 mg kg(-1) (mg L(-1) for
      water) were acquired from 87.6% to 109.1% with relative standard deviation (RSD)
      from 1.9% to 9.5% (n=5), and the limit of detection (LOD, signal to noise
      (S/N)=3) and the limit of quantification (LOQ, S/N=10) were 6.3*10(-4) mg L(-1)
      and 2.09*10(-3) mg L(-1), respectively, which indicates the favorable accuracy,
      precision and sensitivity of the method for effective monitoring of the trace
      amounts of residual trifloxystrobin in the rice paddy. Furthermore, dissipation
      of residual trifloxystrobin was in accordance with the first-order rate equation,
      showing the half-lives from 0.7 to 7.5 days, illustrating that trifloxystrobin
      generally degraded in a rapid rate in the rice paddy. Additionally,
      trifloxystrobin acid identified as the primary metabolite of trifloxystrobin in
      the rice paddy via GC-EI-MS/MS analysis was found to be dominantly accumulated in
      the paddy water and maintained up to 2.41 mg L(-1) within 14 days, suggesting
      that long-term and frequent application of this fungicide may pose a high risk
      towards aquatic organisms in surrounding aqueous ecosystems through paddy
      drainage. Taken together, our data serve as a useful tool for monitoring residual
      trifloxystrobin in rice paddy ecosystem and also provide a basis for in-depth
      understanding of environmental behavior and ecological risk posed by this
      fungicide.

PMID- 25770955
TI  - Detailed comparison of OC/EC aerosol at an urban and a rural Czech background
      site during summer and winter.
AB  - Winter and summer measurements of organic carbon and elemental carbon (OC and EC)
      in PM2.5 were performed in parallel at two sites, the rural background station
      Kosetice and the Prague-Suchdol urban background site, with a 2-h time resolution
      using semi-online field OC/EC analysers. Seasonal and site differences were found
      in the OC and EC contents of PM2.5. Overall, the highest concentrations of both
      OC and EC were during winter at the urban site. The average urban impact was 50%
      for OC and 70% for EC. The summer season gives similar concentrations of OC at
      both sites. However, higher concentrations of EC, caused by higher traffic, were
      found at the urban site with an average urban increase of 50%. Moreover, an
      analysis of four OC fractions depending on the volatility (OC1 - most volatile,
      OC4 - least volatile) and pyrolytic carbon (PC) is provided. A similar level of
      each OC fraction at both sites was found in summer, except for higher OC1 at
      urban and higher PC at the rural site. In winter, the differences between the
      urban and rural sites were dominated by a large increase of the OC1 fraction in
      comparison with the rural site. A diurnal pattern of concentration and share of
      OC1 and PC suggests a prevailing influence of local sources on their
      concentrations at the urban site in winter. The OC3 and OC4 diurnal cycles
      suggest their more regional or long range transport origin in both seasons. The
      prevalent influence of OC1 at any urban site has not been previously reported.
      The minimisation of semi-volatile carbon losses during semi-continuous sampling
      and analysis, in comparison with off-line sampling methods, is a probable reason
      for the observed differences. 

PMID- 25770956
TI  - Limited mouth opening with a square mandible configuration: a case of masticatory
      muscle tendon-aponeurosis hyperplasia.
AB  - Most clinicians throughout the world are probably unaware of the existence of
      masticatory muscle tendon-aponeurosis hyperplasia (MMTAH), potentially leading to
      misdiagnoses such as temporomandibular joint disorder (TMD). Here, we introduce
      this disease from the viewpoint of education. In February 2013, a 39-year-old
      woman presented with limited mouth opening. Her facial configuration was
      characterized by a square mandible. There was no evidence of TMD. Magnetic
      resonance imaging (MRI) showed bilateral enlargement of the masseter muscles.
      Additionally, a 'thick' aponeurosis of the anterior aspect of the masseter muscle
      was noted bilaterally. On maximal mouth opening, intraoral palpation along the
      anterior border of the masseter muscle confirmed a hard cord-like structure,
      consistent with the findings on MRI. MMTAH was diagnosed. When clinicians notice
      limited mouth opening on oral examination, they should be knowledgeable about
      diseases associated with limited mouth opening and a square mandibular
      configuration, such as MMTAH. 

PMID- 25770957
TI  - Effect of a new regeneration process by adsorption-coagulation and flocculation
      on the physicochemical properties and the detergent efficiency of regenerated
      cleaning solutions.
AB  - Reprocessing soiled cleaning-in-place (CIP) solutions has large economic and
      environmental costs, and it would be cheaper and greener to recycle them. In food
      industries, recycling of CIP solutions requires a suitable green process
      engineered to take into account the extreme physicochemical conditions of
      cleaning while not altering the process efficiency. To this end, an innovative
      treatment process combining adsorption-coagulation with flocculation was tested
      on multiple recycling of acid and basic cleaning solutions. In-depth analysis of
      time-course evolutions was carried out in the physicochemical properties
      (concentration, surface tension, viscosity, COD, total nitrogen) of these
      solutions over the course of successive regenerations. Cleaning and disinfection
      efficiencies were assessed based on both microbiological analyses and organic
      matter detachment and solubilization from fouled stainless steel surfaces.
      Microbiological analyses using a resistant bacterial strain (Bacillus subtilis
      spores) highlighted that solutions regenerated up to 20 times maintained the same
      bactericidal efficiency as de novo NaOH solutions. The cleanability of stainless
      steel surfaces showed that regenerated solutions allow better surface
      wettability, which goes to explain the improved detachment and solubilization
      found on different types of organic and inorganic fouling. 

PMID- 25770958
TI  - An integrated system dynamics model developed for managing lake water quality at
      the watershed scale.
AB  - A reliable system simulation to relate socioeconomic development with water
      environment and to comprehensively represent a watershed's dynamic features is
      important. In this study, after identifying lake watershed system processes, we
      developed a system dynamics modeling framework for managing lake water quality at
      the watershed scale. Two reinforcing loops (Development and Investment Promotion)
      and three balancing loops (Pollution, Resource Consumption, and Pollution
      Control) were constituted. Based on this work, we constructed Stock and Flow
      Diagrams that embedded a pollutant load model and a lake water quality model into
      a socioeconomic system dynamics model. The Dianchi Lake in Yunnan Province,
      China, which is the sixth largest and among the most severely polluted freshwater
      lakes in China, was employed as a case study to demonstrate the applicability of
      the model. Water quality parameters considered in the model included chemical
      oxygen demand (COD), total nitrogen (TN), and total phosphorus (TP). The business
      as-usual (BAU) scenario and three alternative management scenarios on spatial
      adjustment of industries and population (S1), wastewater treatment capacity
      construction (S2), and structural adjustment of agriculture (S3), were simulated
      to assess the effectiveness of certain policies in improving water quality.
      Results showed that S2 is most effective scenario, and the COD, TN, and TP
      concentrations in Caohai in 2030 are 52.5, 10.9, and 0.8 mg/L, while those in
      Waihai are 9.6, 1.2, and 0.08 mg/L, with sustained development in the watershed.
      Thus, the model can help support the decision making required in development and
      environmental protection strategies. 

PMID- 25770959
TI  - A novel magnetic adsorbent based on waste litchi peels for removing Pb(II) from
      aqueous solution.
AB  - A new magnetic bioadsorbent, magnetic litchi peel (MLP), was synthesized by
      coating powdered litchi peel with Fe3O4, and was used for removing Pb(II) from
      aqueous solutions. The influencing factors, adsorption isotherms, kinetics, and
      thermodynamics of Pb(II) adsorption by MLP were investigated using batch assays.
      Optimum Pb(II) adsorption by MLP was achieved using a contact time of 120 min, an
      adsorbent dose of 5 g/L, and pH of 6.0. The adsorption equilibrium data conformed
      to the Langmuir isotherm model, yielding a maximum Pb(II) adsorption capacity of
      78.74 mg/g. The adsorption kinetics for Pb(II) adsorption by MLP followed a
      pseudo-second-order model. The thermodynamic results suggested that Pb(II)
      adsorption by MLP was spontaneous and exothermic. Additionally, the magnetic
      adsorbent was easily and rapidly separated out of solution under an external
      magnetic field. 

PMID- 25770960
TI  - Irrigation water quality influences heavy metal uptake by willows in biosolids.
AB  - Phytoextraction is an effective method to remediate heavy metal contaminated
      landscapes but is often applied for single metal contaminants. Plants used for
      phytoextraction may not always be able to grow in drier environments without
      irrigation. This study investigated if willows (Salix x reichardtii A. Kerner)
      can be used for phytoextraction of multiple metals in biosolids, an end-product
      of the wastewater treatment process, and if irrigation with reclaimed and
      freshwater influences the extraction process. A plantation of willows was
      established directly onto a tilled stockpile of metal-contaminated biosolids and
      irrigated with slightly saline reclaimed water (EC ~2 dS/cm) at a wastewater
      processing plant in Victoria, Australia. Biomass was harvested annually and
      analysed for heavy metal content. Phytoextraction of cadmium, copper, nickel and
      zinc was benchmarked against freshwater irrigated willows. The minimum irrigation
      rate of 700 mm per growing season was sufficient for willows to grow and extract
      metals. Increasing irrigation rates produced no differences in total biomass and
      also no differences in the extraction of heavy metals. The reclaimed water
      reduced both the salinity and the acidity of the biosolids significantly within
      the first 12 months after irrigation commenced and after three seasons the
      salinity of the biosolids had dropped to <15% of initial values. A flushing
      treatment to remove excess salts was therefore not necessary. Irrigation had an
      impact on biosolids attributes such as salinity and pH, and that this had an
      influence on metal extraction. Reclaimed water irrigation reduced the biosolid pH
      and this was associated with reductions of the extraction of Ni and Zn, it did
      not influence the extraction of Cu and enhanced the phytoextraction of Cd, which
      was probably related to the high chloride content of the reclaimed water. Our
      results demonstrate that flood-irrigation with reclaimed water was a successful
      treatment to grow willows in a dry climate. However, the reclaimed water can also
      change biosolids properties, which will influence the effectiveness of willows to
      extract different metals. 

PMID- 25770961
TI  - Citizens' distrust of government and their protest responses in a contingent
      valuation study of urban heritage trees in Guangzhou, China.
AB  - Protest response is a common aspect of contingent valuation (CV) studies, which
      has attracted growing attention from scholars worldwide. Distrust of government,
      understood as one of the major reasons for protest response, has been prevalent
      across transitional China experiencing dramatic changes in its economy, society
      and natural environment. Citizen distrust of government would significantly
      hinder the efficiency and validity of the contingent valuation method (CVM)
      application focusing on the provision of public environmental and ecological
      goods in China, as a large proportion of protest responses might be induced.
      Hitherto little has been done to link residents' trust in government to their
      environmental behaviors in developing and transitional economies like China where
      CVM has been increasingly applied to generate meaningful and reliable information
      for integrating both ecological and socioeconomic perspectives into policy
      decisions. This study aims to investigate the discrepancies between protest
      responses induced by distrust of government and non-protest responses, using the
      contingent valuation of heritage trees in Guangzhou as a case. The combination of
      a set of debriefing questions and several attitudinal questions is employed in
      the questionnaire. Based on logit analysis and discriminant analysis, it has been
      found that protestors who distrust government and non-protestors share similar
      salient values associated with urban heritage trees in Guangzhou, especially
      their distinctive historical and cultural values, in comparison with ordinary
      urban trees. Residents with low familiarity with heritage trees (who rarely visit
      sites with heritage trees, know little about management and conservation
      techniques, and consider present management to be ineffective) are likely to act
      as protesters with the "distrust of government" belief. Only if more
      opportunities are provided for residents to obtain access to urban heritage tree
      sites, more information (about urban heritage trees and other environmental and
      ecological goods) is disseminated, and more effective management is implemented,
      can better governmental trust be developed and stronger public participation and
      support secured. The results of this study can shed light on understanding
      protest responses in CV studies and improving the reliability and efficiency of
      CVM in China and other developing countries where a low level of trust in
      government prevails. 

PMID- 25770962
TI  - Olive-pomace harbors bacteria with the potential for hydrocarbon-biodegradation,
      nitrogen-fixation and mercury-resistance: promising material for waste-oil
      bioremediation.
AB  - Olive-pomace, a waste by-product of olive oil industry, took up >40% of its
      weight crude oil. Meanwhile, this material harbored a rich and diverse
      hydrocarbonoclastic bacterial population in the magnitude of 10(6) to 10(7) cells
      g(-1). Using this material for bioaugmentation of batch cultures in crude oil
      containing mineral medium, resulted in the consumption of 12.9, 21.5, 28.3, and
      43% oil after 2, 4, 6 and 8 months, respectively. Similar oil-consumption values,
      namely 11.0, 29.3, 34.7 and 43.9%, respectively, were recorded when a NaNO3-free
      medium was used instead of the complete medium. Hydrocarbonoclastic bacteria
      involved in those bioremediation processes, as characterized by their 16S rRNA
      gene sequences, belonged to the genera Agrococcus, Pseudomonas,
      Cellulosimicrobium, Streptococcus, Sinorhizobium, Olivibacter, Ochrobactrum,
      Rhizobium, Pleomorphomonas, Azoarcus, Starkeya and others. Many of the bacterial
      species belonging to those genera were diazotrophic; they proved to contain the
      nifH-genes in their genomes. Still other bacterial species could tolerate the
      heavy metal mercury. The dynamic changes of the proportions of various species
      during 8 months of incubation were recorded. The culture-independent,
      phylogenetic analysis of the bacterioflora gave lists different from those
      recorded by the culture-dependent method. Nevertheless, those lists comprised
      among others, several genera known for their hydrocarbonoclastic potential, e.g.
      Pseudomonas, Mycobacterium, Sphingobium, and Citrobacter. It was concluded that
      olive-pomace could be applied in oil-remediation, not only as a physical sorbent,
      but also for bioaugmentation purposes as a biological source of
      hydrocarbonoclastic bacteria. 

PMID- 25770963
TI  - Removing heavy metals from wastewaters with use of shales accompanying the coal
      beds.
AB  - A possibility of using clay waste rocks (shales) from coal mines in the removal
      of heavy metals from industrial wastewaters is considered in this paper. Raw and
      calcined (600  degrees C) shales accompanying the coal beds in two Polish coal
      mines were examined with respect to their adsorptive capabilities for Pb, Ni and
      Cu ions. The mineralogical composition of the shales was determined and the
      TG/DTG analysis was carried out. The granulometric compositions of raw and
      calcined shales were compared. Tests of adsorption for various Pb(II), Ni(II) and
      Cu(II) concentrations were conducted and the pH before and after adsorption was
      analyzed. The results indicate that the shales from both coal mines differ in
      adsorptive capabilities for particular metal ions. The calcination improved the
      adsorptive capabilities for lead, but worsened them for nickel. The examined
      shales have good adsorptive capabilities, and could be used as inexpensive
      adsorbents of heavy metal ions, especially in the regions where resources of
      shale are easy accessible in the form of spoil tips. 

PMID- 25770964
TI  - Rhodamine B removal with activated carbons obtained from lignocellulosic waste.
AB  - By-products from the wax production process from carnauba palm (leaves), from the
      extraction of oil from macauba seeds (endocarp) and from pine nut production
      (shell) have been assessed for activated carbon production, using H3PO4 or CaCl2
      for their chemical activation. The resulting activated charcoals have been
      thoroughly characterized by elemental and thermal analysis, X-ray diffraction,
      infrared spectroscopy, electron scanning microscopy and N2 adsorption behavior.
      Subsequently, their adsorption capacity for the removal of rhodamine B (RhB) from
      aqueous solutions has been evaluated by studying different parameters: contact
      time, pH, adsorbent dose, initial dye concentration and solution temperature. The
      adsorption of RhB followed Freundlich's model in all cases. Kinetic studies
      indicate that the pseudo-second order model can be used for describing the
      dynamics of the adsorption process. Thermodynamic parameters have also been
      evaluated, indicating its endothermic and spontaneous nature. Finally, a
      preliminary analysis of the impact of cellulose content in the carbon precursor
      materials has been conducted, by using a mixture of native cellulose with one of
      the lignocellulosic materials. 

PMID- 25770965
TI  - Design, spectral characterization, thermal, DFT studies and anticancer cell line
      activities of Co(II), Ni(II) and Cu(II) complexes of Schiff bases derived from 4
      amino-5-(pyridin-4-yl)-4H-1,2,4-triazole-3-thiol.
AB  - A series of two biologically active Schiff base ligands L(1), L(2) have been
      synthesized in equimolar reaction of 4-amino-5-(pyridin-4-yl)-4H-1,2,4-triazole-3
      thiol with thiophene-2-carbaldehyde and furan-2-carbaldehyde. The synthesized
      Schiff bases were used for complexation with different metal ions like Co(II),
      Ni(II) and Cu(II) by using a molar ratio of ligand: metal as 1:1 and 2:1. The
      characterization of Schiff bases and metal complexes was done by (1)H NMR, UV
      Vis, TGA, IR, mass spectrometry and molar conductivity studies. The in DFT
      studies the geometries of Schiff bases and metal complexes were fully optimized
      with respect to the energy using the 6-31+g(d,p) basis set. On the basis of the
      spectral studies an octahedral geometry has been assigned for Co(II), Ni(II) and
      Cu(II) complexes. The effect of these complexes on proliferation of human breast
      cancer cell line (MCF-7) and human hepatocellular liver carcinoma cell line (Hep
      G2) were studied and compared with those of free ligand. The anticancer cell line
      results reveal that all metal complexes show moderate to significant %
      cytotoxicity on cell line HepG2 and MCF-7. 

PMID- 25770966
TI  - Selectivity enhancement of Arsenazo(III) reagent towards heavier lanthanides
      using polyaminocarboxylic acids: a spectrophotometric study.
AB  - A new study has been conducted to quantify lanthanide(III) ions using Arsenazo
      III-polyaminocarboxylic acid (PACA) system. The study disclosed two different
      analytically important information: (i) lambdamax of lanthanide-Arsenazo III
      complexes for lighter lanthanides like Ce(III) and Nd(III) did not shift from its
      original position on addition of PACA and (ii) for heavier lanthanides like
      Dy(III), Tm(III) and Lu(III) a new lambdamax at 538 nm was observed, while
      wavelengths at 610 nm and 654 nm were disappeared in presence of
      ethylenediaminetertracetic acid (EDTA) and trans-1,2-Diaminocyclohexane-N,N,N',N'
      tetraacetic acid (DCTA), further the intensity of peak decreased with increase in
      lanthanide(III) ion concentration. Effect of ethylene glycol-bis(2
      aminoethylether)-N,N,N',N'-tetraacetic acid (EGTA) and N-(2-hydroxyethyl)
      ethylenediamine-N,N',N'-triacetic acid (EDTA-OH) on Arsenzo(III)-Ln(III) complex
      is very weak and there is no analytically importance of such interaction.
      Moreover, this work confirms that Nd(III) and heavy lanthanides can be
      successfully determined with high accuracy in the working range of concentration
      of these metal ions.

PMID- 25770967
TI  - Green synthesis of SnO2 nanoparticles and its photocatalytic activity of
      phenolsulfonphthalein dye.
AB  - Tin oxide (SnO2) nanoparticles were prepared using Persia Americana seed
      methanolic extract by calcining stannous chloride precursors at 300-500 degrees C
      by green synthesis method. Synthesized SnO2 NPs were confirmed via
      characterization techniques such as UV-visible spectroscopy (UV), X-ray
      diffraction (XRD), Scanning Electron Microscope (SEM) and Energy Dispersive X-ray
      analysis (EDAX). The results of characterization technique states that the
      synthesized nanoparticles were in the size of 4 nm and further we have undergone
      catalytic degradation of organic dye named phenolsulfonphthalein (phenol red).
      The result showed that SnO2 NPs shows much degradation activity by the catalytic
      action of long UV exactly at 365 nm.

PMID- 25770968
TI  - The EF-hand Ca(2+)-binding protein super-family: a genome-wide analysis of gene
      expression patterns in the adult mouse brain.
AB  - In mice, 249 putative members of the superfamily of EF-hand domain Ca(2+)-binding
      proteins, manifesting great diversity in structure, cellular localization and
      functions have been identified. Three members in particular, namely, calbindin
      D28K, calretinin and parvalbumin, are widely used as markers for specific
      neuronal subpopulations in different regions of the brain. The aim of the present
      study was to compile a comprehensive atlas of the gene-expression profiles of the
      entire EF-hand gene superfamily in the murine brain. This was achieved by a
      meticulous examination of the in-situ hybridization images in the Allen Brain
      Atlas database. Topographically, our analysis focused on the olfactory bulb,
      cerebral cortex (barrel cortex in the primary somatosensory area), basal ganglia,
      hippocampus, amygdala, thalamus, hypothalamus, cerebellum, midbrain, pons and
      medulla, and on clearly identifiable sub-structures within each of these areas.
      The expression profiles of four family-members, namely hippocalcin-like 4,
      neurocalcin-delta, plastin 3 and tescalcin, that have not been hitherto reported,
      at either the mRNA (in-situ-hybridization) or the protein (immunohistochemical)
      levels, are now presented for the first time. The fruit of our analysis is a
      document in which the gene-expression profiles of all members of the EF-hand
      family genes are compared, and in which future possible neuronal markers for
      specific cells/brain areas are identified. The assembled information could afford
      functional clues to investigators, conducive to further experimental pursuit.

PMID- 25770969
TI  - Lovastatin suppresses the aberrant tau phosphorylation from FTDP-17 mutation and
      okadaic acid-induction in rat primary neurons.
AB  - Statins are a class of cholesterol-lowering drugs and have been suggested
      therapeutic use for neurodegenerative diseases including Alzheimer's disease
      (AD). Our recent studies revealed a neuronal protective effect of lovastatin
      (LOV) from N-methyl-d-aspartic acid (NMDA) excitotoxicity. The neuroprotective
      mechanism of statins, however, is far unknown. Here we demonstrated that LOV
      suppressed the aberrant tau phosphorylation both from frontotemporal dementia and
      Parkinsonism linked to chromosome 17 (FTDP-17) mutation and okadaic acid (OA)
      induction in cultured rat primary neurons. The protective effect of LOV occurred
      at multiple pathological sites of tau protein, including Tyr181, Tyr231
      Ser202/Tyr205, Tyr212/Ser214 and Ser396/Ser404. Further analysis revealed that
      the potential mechanism of the suppressive effect of LOV resulted from two
      aspects, activating OA-inhibited protein phosphatase 2A (PP2A) activity and
      attenuating OA-induced activity of tau kinases CDK5/P25 and CDK2/4, but not
      glycogen synthase kinase 3beta (GSK3beta). These findings give new insights into
      the molecular mechanism of LOV-mediated neuroprotective effect and provide
      experimental evidence for its therapeutic use in AD.

PMID- 25770970
TI  - Understanding heterogeneity in the effects of birth weight on adult cognition and
      wages.
AB  - A large economics literature has shown long term impacts of birth weight on adult
      outcomes, including IQ and earnings that are often robust to sibling or twin
      fixed effects. We examine potential mechanisms underlying these effects by
      incorporating findings from the genetics and neuroscience literatures. We use a
      sample of siblings combined with an "orchids and dandelions hypothesis", where
      the IQ of genetic dandelions is not affected by in utero nutrition variation but
      genetic orchids thrive under advantageous conditions and wilt in poor conditions.
      Indeed, using variation in three candidate genes related to neuroplasticity
      (APOE, BDNF, and COMT), we find substantial heterogeneity in the associations
      between birth weight and adult outcomes, where part of the population (i.e.,
      "dandelions") is not affected by birth weight variation. Our results help uncover
      why birth weight affects adult outcomes. 

PMID- 25770971
TI  - Genealogical histories in structured populations.
AB  - In genealogies of genes sampled from structured populations, lineages coalesce at
      rates dependent on the states of the lineages. For migration and coalescence
      events occurring on comparable time scales, for example, only lineages residing
      in the same deme of a geographically subdivided population can have descended
      from a common ancestor in the immediately preceding generation. Here, we explore
      aspects of genealogical structure in a population comprising two demes, between
      which migration may occur. We use generating functions to obtain exact densities
      and moments of coalescence time, number of mutations, total tree length, and age
      of the most recent common ancestor of the sample. We describe qualitative
      features of the distribution of gene genealogies, including factors that
      influence the geographical location of the most recent common ancestor and
      departures of the distribution of internode lengths from exponential. 

PMID- 25770972
TI  - The Choice Between an Academic Versus Private Practice Career in Cardiology: A
      Fellow's Perspective.
AB  - This study is written in editorial style from the perspective of a fellow-in
      training. The editorial profiles specific principles to assist other fellows as
      they deliberate on the choice between an academic versus private practice career
      in cardiovascular medicine. Among the key principles are: outlining the general
      differences between academic and nonacademic careers, identifying the areas of
      overlap and change, understanding the heterogeneity within academia, and choosing
      the opportunities that invest in your success. Emphasis is also placed on
      outlining ways in which one can advance their competitive frontier in cardiology.
      In conclusion, this editorial emphasizes guiding principles to help fellows-in
      training as they search for a career in cardiovascular medicine that fosters
      growth and empowers them to achieve their professional goals. 

PMID- 25770973
TI  - Usefulness of the Left Anterior Descending Artery Wrapping Around the Left
      Ventricular Apex to Predict Adverse Clinical Outcomes in Patients With Anterior
      Wall ST-Segment Elevation Myocardial Infarction (an INFUSE-AMI Substudy).
AB  - The relation between left anterior descending coronary artery (LAD) anatomic
      features and clinical outcomes in patients with anterior ST-segment elevation
      myocardial infarction has not been fully investigated. The Intracoronary
      Abciximab and Aspiration Thrombectomy in Patients With Large Anterior Myocardial
      Infarction (INFUSE-AMI) trial randomized 452 patients with anterior ST-segment
      elevation myocardial infarctions who underwent mechanical revascularization to
      intralesional abciximab versus no abciximab and to manual thrombus aspiration
      versus no aspiration. The primary end point was infarct size (percentage left
      ventricular mass) on contrast magnetic resonance imaging at 30 days. "Wraparound
      LAD" was defined as an LAD reaching the apex and supplying the apical inferior
      aspect of the heart. Among complete data available in 338 patients, 258 (76.3%)
      had wraparound LADs. Global infarct size (17.4% vs 16.1%, p = 0.64) and the left
      ventricular ejection fraction (49.7% vs 48.7%, p = 0.98) by contrast magnetic
      resonance imaging at 30 days were comparable between patients with and those
      without wraparound LADs. Regional apical anterior infarct size was comparable
      (59.5% vs 55.8%, p = 0.559) between the groups; however, apical septal (61.3% vs
      48.9%, p = 0.005), apical inferior (19.0% vs 3.7%, p <0.0001), and apical lateral
      (12.2% vs 4.8%, p = 0.0584) infarct sizes were larger in patients with wraparound
      LADs compared with those with nonwraparound LADs. The incidence of new-onset
      severe heart failure at 1 year was significantly higher in patients with compared
      with those without wraparound LADs (6.3% vs 0%, p = 0.02). In conclusion, in
      patients with anterior ST-segment elevation myocardial infarctions, as compared
      with the LAD not supplying the inferior aspect of the heart, a wraparound LAD was
      associated with a larger left ventricular apex infarct size, resulting in worse
      adverse events at 1 year.

PMID- 25770974
TI  - Comparison among patients>=75 years having percutaneous coronary angioplasty
      using drug-eluting stents versus bare metal stents.
AB  - Limited data are available on long-term efficacy and safety of drug-eluting
      stents (DES) in elderly patients who underwent PCI. A total of 635 consecutive
      patients aged >=75 years who underwent PCI were enrolled at 2 European centers.
      Of these, 170 patients received at least 1 DES, whereas 465 patients received
      bare metal stent (BMS) only. Primary end point was the incidence of net adverse
      clinical events (NACE), defined as the occurrence of ischemic events or bleeding
      events, and was compared at a median follow-up of 31.2 months. Clinical follow-up
      information was available in 593 patients (93.4%). The duration of dual
      antiplatelet therapy was 12.3+/-5.1 months in the DES group and 3.8+/-7.4 months
      in the BMS group. The Kaplan-Meier estimate of NACE at 5 years was significantly
      lower in DES-treated patients (40.5%) than in BMS-treated patients (55.7%;
      p=0.009). This benefit was driven by a significant reduction in myocardial
      infarction (8.6% vs 16.6%; p=0.038) and target vessel revascularization rates
      (7.9% vs 21.9%; p=0.003) in the DES group, with no significant increase in the
      incidence of bleeding events (13.8% vs 12.2%; p=0.882). These results were
      confirmed at propensity score-adjusted Cox proportional hazard analysis. In
      conclusion, in patients>=75 years, the use of DES compared with BMS seems to
      reduce myocardial infarction and repeat revascularization rates at long-term
      follow-up, without an increase in bleeding despite longer duration of dual
      antiplatelet therapy. This net clinical benefit, resulting from persistent
      efficacy and safety over time, may support the use of DES as a reasonable option
      in patients>=75 years.

PMID- 25770975
TI  - Transcriptional and biochemical markers in transplanted Perca flavescens to
      characterize cadmium- and copper-induced oxidative stress in the field.
AB  - Despite recent progress achieved in elucidating the mechanisms underlying local
      adaptation to pollution, little is known about the evolutionary change that may
      be occurring at the molecular level. The goal of this study was to examine
      patterns of gene transcription and biochemical responses induced by metal
      accumulation in clean yellow perch (Perca flavescens) and metal depuration in
      contaminated fish in a mining and smelting region of Canada. Fish were collected
      from a reference lake (lake Opasatica) and a Cd, Cu and Zn contaminated lake
      (lake Dufault) located in the Rouyn-Noranda region (Qc, Canada) and caged for one
      or four weeks in their own lake or transplanted in the other lake. Free-ranging
      fish from the same lakes were also collected. Kidney Cd and Cu concentrations in
      clean fish caged in the contaminated lake increased with the time of exposure,
      but metal depuration did not occur in contaminated fish caged in the clean lake.
      After 4 weeks, the major retinoid metabolites analysed, the percentage of free
      dehydroretinol (dROH) and the retinol dehydrogenase-2 (rdh-2) transcription level
      in liver decreased in clean fish transplanted into the metal-contaminated lake,
      suggesting that metal exposure negatively impacted retinoid metabolism. However,
      we observed an increase in almost all of the retinoid parameters analysed in fish
      from the metal-impacted lake caged in the same lake, which we interpret as an
      adaptation response to higher ambient metal concentration. In support of this
      hypothesis, liver transcription levels of microsomal glutathione-S-transferase-3
      (mgst-3) and glucose-6-phosphate dehydrogenase (g6pdh) were enhanced in clean
      fish transplanted into the metal-contaminated lake and this up-regulation was
      accompanied by an increase in the activities of corresponding enzymes, involved
      in antioxidant response. However, although in the same fish the transcription
      level of Cu/Zn superoxide dismutase (Cu/Zn sod) was also increased, this did not
      lead to a change in the activity of the SOD enzyme, suggesting that this
      upregulation was aimed at maintaining SOD-related antioxidant capacities. In
      contrast, the transcription level of the cat gene, which did not change in
      contaminated fish, did not compensate for the decrease of CAT activity. After 4
      weeks of exposure, some plastic responses of the clean fish were observed when
      they were transplanted in the metal-contaminated lake. However, probably as a
      consequence of the prior 80 years of exposure to metals, the contaminated
      population showed a limited plastic response in the expression of the majority of
      the candidate genes tested, when they were transplanted in the reference lake.
      The overall findings of this field investigation highlight how yellow perch
      molecularly and biochemically responded to a sudden or relatively long-term
      exposure (4 weeks) to a cocktail of metals. 

PMID- 25770976
TI  - Women and smoking-prices and health warning messages: evidence from Spain.
AB  - OBJECTIVE: In Spain, fewer men are smoking every year yet the number of women
      smokers remains relatively high. This paper examines the impact of two anti
      smoking policies (increased prices and obligatory pictorial health warning
      labels) on womens smoking decisions; generation cohorts are used to elucidate the
      determinants of those decisions. DATA SOURCE: We have drawn 48,755 observations
      of women living in Spain from the Spanish National Health Surveys of 2001, 2003,
      2006 and 2011. DATA SYNTHESIS: Among the main results, we highlight that
      belonging to a particular generation modulates the manner in which individual
      characteristics and tobacco policies determine smoking decisions. For example,
      women's smoking was not considered as socially acceptable until the 1960s and
      therefore older women have lower smoking rates. However, for the younger female
      cohorts (generations X and Y) smoking was seen as an act of rebellion and
      modernity, so women belonging to these groups, irrespective of educational level,
      are more likely to smoke. CONCLUSIONS: The price of cigarettes and pictorial
      health warning labels on cigarette packets also influence the smoking behaviour
      of Spanish women.

PMID- 25770977
TI  - Bidimensional and Doppler ultrasonographic evaluation of postpartum uterine
      involution in the queen.
AB  - The aim of this study was to describe bidimensional and Doppler ultrasonographic
      changes of uterine involution during normal feline puerperium. Secondary, the
      postpartum vaginal discharge was described. Twelve pregnant female cats were
      included in this study. After queening, vulvar discharge was grossly and
      microscopically examined daily. Bidimensional and Doppler ultrasonographic
      examinations of the uterus were performed on Days -4 to -2, 4, 11, 18, and 25
      from parturition. Total uterine diameter, uterine wall thickness, uterine lumen
      contents, peak systolic velocity, end diastolic velocity, and resistance index of
      uterine arteries were measured. The cats presented serosanguineous vulvar
      discharge for a mean of 3 +/- 1 days after parturition, and the cytology revealed
      70% to 80% of erythrocytes, which progressively decreased up to Day 13.
      Immediately after parturition, there were less than 20% neutrophils, and this
      percentage gradually diminished to 0% to 1% at the end of the study. Uterine
      total diameter diminished up to Day 25 (P < 0.01), when ultrasonographic uterine
      dimensions were similar to that of anestrus. A progressive decrease of uterine
      wall thickness (P < 0.05), uterine lumen contents (P < 0.01), peak systolic
      velocity (P < 0.01), and end diastolic velocity (P < 0.01) was found throughout
      the study period. Conversely, resistance index increased during the first week
      after parturition (P < 0.01). It is concluded that the uterine artery blood flow
      progressively decreased during the first 25 days after parturition, which was
      associated with the bidimensional ultrasonographic regression of the organ.
      Although lochial discharge disappeared far before ultrasonographic involution,
      cytologic findings further corroborated the duration of this regression process.

PMID- 25770978
TI  - Gas exchange pattern transitions in the workers of the harvester termite.
AB  - The evolutionary genesis and the current adaptive significance of the use of the
      discontinuous gas exchange cycle (DGC) for respiration by insects is the subject
      of intense debate. Years of research have resulted in several leading hypotheses,
      one of which is the emergent-property hypothesis. This hypothesis states that DGC
      is an emergent property or consequence of interactions between the O2 and CO2 set
      points that regulate spiracular function, i.e. opening and closing. Workers of
      the harvester termite, Hodotermes mossambicus were selected as a model to test
      this hypothesis. The respiratory patterns of major workers, investigated using
      flow-through respirometry, were obtained at 100% relative humidity (RH) under
      varying temperature to evaluate the assumptions of the emergent-property
      hypothesis. Metabolic rate, measured as VCO2 increased significantly after 15 
      degrees C. As VCO2 increased in response to increasing temperature and activity,
      the gas exchange pattern displayed by workers transitioned to a continuous gas
      exchange. A true DGC, defined as showing all three phases and a coefficient of
      variation value close to 2, was not expressed under the experimental conditions.
      The conclusion drawn from this study of termite workers is that changes in
      respiratory patterns are most likely an emergent property of the insects' nervous
      and respiratory system.

PMID- 25770979
TI  - Identification of two juvenile hormone inducible transcription factors from the
      silkworm, Bombyx mori.
AB  - Juvenile hormone (JH) regulates many physiological processes in insects. However,
      the signal cascades in which JH is active have not yet been fully elucidated,
      particularly in comparison to another major hormone ecdysteroid. Here we
      identified two JH inducible transcription factors as candidate components of JH
      signaling pathways in the silkworm, Bombyx mori. DNA microarray analysis showed
      that expression of two transcription factor genes, E75 and Enhancer of split
      mbeta (E(spl)mbeta), was induced by juvenile hormone I (JH I) in NIAS-Bm-aff3
      cells. Real time RT-PCR analysis confirmed that expression of four E75 isoforms
      (E75A, E75B, E75C and E75D) and E(spl)mbeta was 3-8 times greater after JH I
      addition. Addition of the protein synthesis inhibitor cycloheximide did not
      suppress JH-induced expression of the genes, indicating that they were directly
      induced by JH. JH-induced expression of E75 and E(spl)mbeta was also observed in
      four other B. mori cell lines and in larval hemocytes of final instar larvae.
      Notably, E75A expression was induced very strongly in larval hemocytes by topical
      application of the JH analog fenoxycarb; the level of induced expression was
      comparable to that produced by feeding larvae with 20-hydroxyecdysone. These
      results suggest that E75 and E(spl)mbeta are general and direct target genes of
      JH and that the transcription factors encoded by these genes play important roles
      in JH signaling. 

PMID- 25770980
TI  - How to escape from the host nest: imperfect chemical mimicry in eucharitid
      parasitoids and exploitation of the ants' hygienic behavior.
AB  - Communication in ants is based to a great extent on chemical compounds.
      Recognition of intruders is primarily based on cuticular hydrocarbon (CHC)
      profile matching but is prone to being cheated. Eucharitid wasps are specific
      parasitoids of the brood of ants; the immature stages are either well integrated
      within the colony or are protected within the host cocoons, whereas adult wasps
      at emergence must leave their host nest to reproduce and need to circumvent the
      ant recognition system to escape unscathed. The behavioral interactions between
      eucharitid wasps and workers of their host, the Neotropical ant Ectatomma
      tuberculatum, are characterized. In experimental bioassays, newly emerged
      parasitoids were not violently aggressed. They remained still and were grabbed by
      ants upon contact and transported outside the nest; host workers were even
      observed struggling to reject them. Parasitoids were removed from the nest within
      five minutes, and most were unharmed, although two wasps (out of 30) were killed
      during the interaction with the ants. We analyzed the CHCs of the ant and its two
      parasitoids, Dilocantha lachaudii and Isomerala coronata, and found that although
      wasps shared all of their compounds with the ants, each wasp species had typical
      blends and hydrocarbon abundance was also species specific. Furthermore, the
      wasps had relatively few CHCs compared to E. tuberculatum (22-44% of the host
      components), and these were present in low amounts. Wasps, only partially
      mimicking the host CHC profile, were immediately recognized as alien and actively
      removed from the nest by the ants. Hexane-washed wasps were also transported to
      the refuse piles, but only after being thoroughly inspected and after most of the
      workers had initially ignored them. Being recognized as intruder may be to the
      parasitoids' advantage, allowing them to quickly leave the natal nest, and
      therefore enhancing the fitness of these very short lived parasitoids. We suggest
      that eucharitids take advantage of the hygienic behavior of ants to quickly
      escape from their host nests. 

PMID- 25770982
TI  - Discussion.

PMID- 25770981
TI  - Association between changes in exposure to air pollution and biomarkers of
      oxidative stress in children before and during the Beijing Olympics.
AB  - It is not known whether exposure to air pollutants causes systemic oxidative
      stress in children. We investigated the association between exposure to air
      pollution and biomarkers of oxidative stress in relation to a governmental air
      quality intervention implemented during the 2008 Beijing Olympic Games. We
      studied 36 schoolchildren during 5 time periods before and during the Olympic
      Games in Beijing (June 2007-September 2008). The oxidative stress biomarkers 8
      oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) and malondialdehyde were measured in
      urine samples collected daily during each period. Generalized estimating
      equations were used to examine the relationship between repeated biomarker
      measurements and ambient air pollutant levels. During the Olympic intervention
      period, substantial reductions in air pollution (-19% to -72%), urinary 8-oxodG
      concentrations (-37.4%; 95% confidence interval: -53.5, -15.7), and urinary
      malondialdehyde concentrations (-25.3%; 95% confidence interval: -34.3, -15.1)
      were found. Malondialdehyde and 8-oxodG were significantly associated with
      concentrations of black carbon, fine particulate matter with an aerodynamic with
      diameter less than 2.5 MUm, sulfur dioxide, nitrogen dioxide, and carbon
      monoxide. Biomarker changes per each interquartile-range increase in pollutants
      were largest at lag 0 or lag 1. In a 2-pollutant model, the most robust
      associations were for black carbon. These findings suggest that exposure to black
      carbon leads to systemic oxidative stress in children.

PMID- 25770983
TI  - Use of the Flixene vascular access graft as an early cannulation solution.
AB  - OBJECTIVE: The primary end points of this study were safety and efficacy of early
      cannulation of the Flixene graft (Maquet-Atrium Medical, Hudson, NH). Secondary
      end points were complications and patency. METHODS: This is a prospective single
      center nonrandomized study. Study data included patient characteristics; history
      of vascular access; operative technique; interval between implantation and
      initial cannulation; complications; and patency at 1 month, 3 months, and every 6
      months. Patency rates were estimated by the Kaplan-Meier method. RESULTS: Between
      January 2011 and September 2013, a total of 46 Flixene grafts were implanted in
      44 patients (27 men) with a mean age of 63 years. The implantation site was the
      upper arm in 67% of cases, the forearm in 11%, and the thigh in 22%. Seven grafts
      were never cannulated during the study period. Of the remaining 39 grafts, 32
      (82%) were successfully cannulated within the first week after implantation,
      including 16 (41%) on the first day. The median interval from implantation to
      initial cannulation was 2 days (interquartile range, 1-3 days). The median follow
      up was 223.5 days (interquartile range, 97-600 days). Five hematomas occurred,
      but only one required surgical revision. Primary assisted and secondary patency
      rates were 65% and 86%, respectively, at 6 months and 56% and 86%, respectively,
      at 1 year. CONCLUSIONS: This study suggests that cannulation of the Flixene graft
      within 1 week after implantation is safe and effective. Early cannulation avoids
      or shortens the need for a temporary catheter. One-year patency rates appeared to
      be comparable to those achieved with conventional grafts, but long-term follow-up
      and randomized controlled studies will be needed to confirm this finding.

PMID- 25770985
TI  - Discussion.

PMID- 25770984
TI  - Incidence, outcomes, and effect on quality of life of cranial nerve injury in the
      Carotid Revascularization Endarterectomy versus Stenting Trial.
AB  - OBJECTIVE: Cranial nerve injury (CNI) is the most common neurologic complication
      of carotid endarterectomy (CEA) and can cause significant chronic disability.
      Data from prior randomized trials are limited and provide no health-related
      quality of life (HRQOL) outcomes specific to CNI. Incidence of CNIs and their
      outcomes for patients in the Carotid Revascularization Endarterectomy vs Stenting
      Trial (CREST) were examined to identify factors predictive of CNI and their
      impact on HRQOL. METHODS: Incidence of CNIs, baseline and procedural
      characteristics, outcomes, and HRQOL scores were evaluated in the 1151 patients
      randomized to CEA and undergoing surgery <=30 days. Patients with CNI were
      identified and classified using case report forms, adverse event data, and
      clinical notes. Baseline and procedural characteristics were compared using
      descriptive statistics. Clinical outcomes at 1 and 12 months were analyzed. All
      data were adjudicated by two neurologists and a vascular surgeon. HRQOL was
      evaluated using the Medical Outcomes Short-Form 36 (SF-36) Health Survey to
      assess general health and Likert scales for disease-specific outcomes at 2 weeks,
      4 weeks, and 12 months after CEA. The effect of CNI on SF-36 subscales was
      evaluated using random effects growth curve models, and Likert scale data were
      compared by ordinal logistic regression. RESULTS: CNI was identified in 53
      patients (4.6%). Cranial nerves injured were VII (30.2%), XII (24.5%), and IX/X
      (41.5%), and 3.8% had Horner syndrome. CNI occurred in 52 of 1040 patients (5.0%)
      receiving general anesthesia and in one of 111 patients (0.9%) operated on under
      local anesthesia (P = .05). No other predictive baseline or procedural factors
      were identified. Deficits resolved in 18 patients (34%) at 1 month and in 42 of
      52 patients (80.8%) by 1 year. One patient died before the 1-year follow-up
      visit. The HRQOL evaluation showed no statistical difference between groups with
      and without CNI at any interval. By Likert scale analysis, the group with CNI
      showed a significant difference in the difficulty eating/swallowing parameter at
      2 and 4 weeks (P < .001) but not at 1 year. CONCLUSIONS: In CREST, CNI occurred
      in 4.6% of patients undergoing CEA, with 34% resolution at 30 days and 80.8% at 1
      year. The incidence of CNI was significantly higher in patients undergoing
      general anesthesia. CNI had a small and transient effect on HRQOL, negatively
      affecting only difficulty eating/swallowing at 2 and 4 weeks but not at 1 year.
      On the basis of these findings, we conclude that CNI is not a trivial consequence
      of CEA but rarely results in significant long-term disability.

PMID- 25770986
TI  - Outcomes after stent graft therapy for dissection-related aneurysmal degeneration
      in the descending thoracic aorta.
AB  - OBJECTIVE: Stent graft therapy has emerged as an alternative to open surgery in
      the management of chronic dissection-related aneurysmal degeneration (DRAD) in
      the descending thoracic aorta (DTA). The incidence of perioperative
      complications, need for secondary aortic intervention (SAI), and rate of
      aneurysmal false-lumen thrombosis have not been thoroughly described. METHODS:
      Perioperative and midterm outcomes in patients who underwent stent graft therapy
      for chronic DRAD DTA at a single institution between January 2006 and September
      2013 were retrospectively analyzed. Preoperative anatomic factors, including the
      number of visceral and renal side branches off the false lumen, and false lumen
      volume, were analyzed for their ability to predict treatment failure. Treatment
      failure was defined as death, need for a SAI, and failure to achieve thrombosis
      of the DRAD DTA. Treatment success was defined as thrombosis of the false lumen
      in the area of the DRAD DTA with stability or a decrease in the maximum diameter
      of the DRAD DTA. RESULTS: During the study period, 47 patients underwent stent
      graft therapy for chronic DRAD DTA. Patients were a mean age of 58.3 +/- 11.7
      years, 74.5% (n = 35) were male, and 14.9% (n = 7) had a history of connective
      tissue disease. The left subclavian artery was covered in 48.9% (n = 23), and
      revascularization was performed in 87.0% (n = 20). Spinal drains were used in
      74.5% (n = 35). Spinal cord ischemia developed in 6.4% (n = 3), which resolved in
      two and improved in one. No retrograde aortic dissections occurred. The 30-day
      mortality was 4.3% (n = 2); one death was in a patient with rupture. Mean
      clinical follow-up was 35.1 +/- 20.9 months. The 5-year Kaplan-Meier survival was
      89% +/- 5%. Treatment failure occurred in 18 patients (38.3%): 9 required SAIs, 6
      did not have thrombosis of the false lumen in the area of the DRAD DTA, and 4
      died, with 1 patient dying during a SAI. No preoperative anatomic factor
      predicted treatment failure. The 5-year freedom from treatment failure was 54% +/
      9%. Including the nine patients who underwent SAI, treatment success was
      achieved in 85.2% of patients. CONCLUSIONS: In this single-center experience of
      stent graft therapy for chronic DRAD DTA, treatment success was achieved in 85%
      of patients after a SAI rate of 20%. No preoperative anatomic factor predicted
      treatment failure, which occurred in almost 40% of the patients. Identifying
      predictors of treatment failure may improve future outcomes.

PMID- 25770987
TI  - A prospective randomized study of heparin-bonded graft (Propaten) versus standard
      graft in prosthetic arteriovenous access.
AB  - OBJECTIVE: Prosthetic grafts continue to be required for hemodialysis access when
      the options for native fistulas have been exhausted. The inferior long-term
      patency of grafts makes the possibility of preventing occlusion with heparin
      bonded grafts an attractive alternative. We carried out a prospective randomized
      study to compare the patency of standard grafts with heparin-bonded grafts.
      METHODS: Patients with end-stage renal failure requiring a prosthetic access were
      randomized to receive either a standard expanded polytetrafluorethylene (ePTFE)
      graft or a heparin-bonded ePTFE graft. Patients were enrolled from June 2007
      until November 2011 and were followed up until July 2013, when the study
      concluded. RESULTS: In this study, 160 patients were randomized and followed up
      for a median of 23.5 months. No patient was lost to follow-up. Primary patency
      was 35% and 14% for heparin-bonded grafts and 29% and 12% for standard ePTFE
      grafts at 6 and 12 months, respectively (P = .48). Assisted primary patency was
      54%, 41%, and 27% for heparin-bonded grafts and 41%, 30%, and 23% for standard
      grafts at 12, 24, and 36 months, respectively (P = .12). Secondary patency was
      83%, 83%, and 81% for heparin-bonded grafts and 81%, 73%, and 68% for standard
      grafts at 12, 24, and 36 months, respectively (P = .33). There were significantly
      fewer thromboses in heparin-bonded grafts during the first 5 months (P = .020).
      Of 80 standard grafts, 24 were eventually abandoned vs 17 heparin-bonded grafts
      (P = .188). Bleeding complications, infections, and intervention rates were
      similar in both groups. CONCLUSIONS: Heparin-bonded grafts demonstrated a trend
      to improved patency, but the difference was not statistically significant.
      Heparin-bonded grafts had a significantly lower early thrombosis rate that was
      sustained only for the first 5 months of follow-up.

PMID- 25770988
TI  - Discharge education for older people and family members in emergency department:
      A cross-sectional study.
AB  - INTRODUCTION: Older patients are a major patient group in emergency settings in
      Finland. Family members have a crucial part to play when older people are
      discharged home. Discharge education is common practice within discharge planning
      in emergency department (ED). Discharge planning is associated with patient
      outcomes, but little is known about discharge education as such. The purpose of
      this study was to examine the association of discharge education with discharge
      readiness among older patients and their family members in an emergency setting
      in Finland. METHODS: This cross-sectional study was performed in two EDs.
      Questionnaire data were collected from patients over 75 (N = 135) and their
      family members (N = 128) to examine the level of discharge education, and to see
      how discharge education was associated with discharge readiness. Descriptive and
      non-parametric methods were used. RESULTS: One in four older patients and 40 per
      cent of family members received no discharge education. Nevertheless, discharge
      education was associated with a higher level of discharge readiness, both among
      patients and family members. DISCUSSION: ED personnel should give more focus to
      discharge education when planning the discharge of older patients in order to
      facilitate better discharge readiness.

PMID- 25770989
TI  - MEG-compatible pneumatic stimulator to elicit passive finger and toe movements.
AB  - Magnetoencephalographic (MEG) signals recorded from the primary sensorimotor
      (SM1) cortex are coherent with kinematics of both active and passive finger
      movements. The coherence mainly reflects movement-related proprioceptive
      afference to the cortex. Here we describe a novel MEG-compatible stimulator to
      generate computer-controlled passive finger and toe movements that can be used as
      stimuli in functional brain-imaging experiments. The movements are produced by
      pneumatic artificial muscle (PAM), elastic actuator that shortens with increasing
      air pressure. To test the applicability of the stimulator to functional brain
      imaging, 4-min trains of passive repetitive 5-mm flexion-extension movements of
      the right and left index finger and the right hallux were produced at 3Hz while
      the subject's brain activity was measured with whole-scalp MEG and finger or toe
      kinematics with an accelerometer. In all ten subjects studied, statistically
      significant coherence (up to 0.78) occurred between the accelerometer and MEG
      signals at the movement frequency or its first harmonic. Sources of coherent
      activity were in the contralateral hand or foot SM1 cortices. Movement-evoked
      fields elicited with intermittent movements of the right index finger (once every
      3.2-4.0s; mean+/-SD peak response latency 88+/-25ms) were co-located with the
      respective coherent sources. We further moved the right index finger at 3, 6, and
      12Hz (movement ranges 5, 3, and 2mm, respectively), and analyzed the first 1, 2,
      and 4-min epochs of data. One minute of data was sufficient to locate the left
      hand area of the SM1 cortex at all movement frequencies. Sound-induced spurious
      coherence was reliably ruled out in a control experiment. Our novel movement
      stimulator thus provides a robust and reliable tool to track proprioceptive
      afference to the cortex and to locate the SM1 cortex. 

PMID- 25770990
TI  - Evaluation of ICA-AROMA and alternative strategies for motion artifact removal in
      resting state fMRI.
AB  - We proposed ICA-AROMA as a strategy for the removal of motion-related artifacts
      from fMRI data (Pruim et al., 2015). ICA-AROMA automatically identifies and
      subsequently removes data-driven derived components that represent motion-related
      artifacts. Here we present an extensive evaluation of ICA-AROMA by comparing our
      strategy to a range of alternative strategies for motion-related artifact
      removal: (i) no secondary motion correction, (ii) extensive nuisance regression
      utilizing 6 or (iii) 24 realignment parameters, (iv) spike regression
      (Satterthwaite et al., 2013a), (v) motion scrubbing (Power et al., 2012), (vi)
      aCompCor (Behzadi et al., 2007; Muschelli et al., 2014), (vii) SOCK
      (Bhaganagarapu et al., 2013), and (viii) ICA-FIX (Griffanti et al., 2014; Salimi
      Khorshidi et al., 2014), without re-training the classifier. Using three
      different functional connectivity analysis approaches and four different multi
      subject resting-state fMRI datasets, we assessed all strategies regarding their
      potential to remove motion artifacts, ability to preserve signal of interest, and
      induced loss in temporal degrees of freedom (tDoF). Results demonstrated that ICA
      AROMA, spike regression, scrubbing, and ICA-FIX similarly minimized the impact of
      motion on functional connectivity metrics. However, both ICA-AROMA and ICA-FIX
      resulted in significantly improved resting-state network reproducibility and
      decreased loss in tDoF compared to spike regression and scrubbing. In comparison
      to ICA-FIX, ICA-AROMA yielded improved preservation of signal of interest across
      all datasets. These results demonstrate that ICA-AROMA is an effective strategy
      for removing motion-related artifacts from rfMRI data. Our robust and
      generalizable strategy avoids the need for censoring fMRI data and reduces motion
      induced signal variations in fMRI data, while preserving signal of interest and
      increasing the reproducibility of functional connectivity metrics. In addition,
      ICA-AROMA preserves the temporal non-artifactual time-series characteristics and
      limits the loss in tDoF, thereby increasing statistical power at both the subject
      and the between-subject analysis level. 

PMID- 25770991
TI  - ICA-AROMA: A robust ICA-based strategy for removing motion artifacts from fMRI
      data.
AB  - Head motion during functional MRI (fMRI) scanning can induce spurious findings
      and/or harm detection of true effects. Solutions have been proposed, including
      deleting ('scrubbing') or regressing out ('spike regression') motion volumes from
      fMRI time-series. These strategies remove motion-induced signal variations at the
      cost of destroying the autocorrelation structure of the fMRI time-series and
      reducing temporal degrees of freedom. ICA-based fMRI denoising strategies
      overcome these drawbacks but typically require re-training of a classifier,
      needing manual labeling of derived components (e.g. ICA-FIX; Salimi-Khorshidi et
      al. (2014)). Here, we propose an ICA-based strategy for Automatic Removal of
      Motion Artifacts (ICA-AROMA) that uses a small (n=4), but robust set of
      theoretically motivated temporal and spatial features. Our strategy does not
      require classifier re-training, retains the data's autocorrelation structure and
      largely preserves temporal degrees of freedom. We describe ICA-AROMA, its
      implementation, and initial validation. ICA-AROMA identified motion components
      with high accuracy and robustness as illustrated by leave-N-out cross-validation.
      We additionally validated ICA-AROMA in resting-state (100 participants) and task
      based fMRI data (118 participants). Our approach removed (motion-related)
      spurious noise from both rfMRI and task-based fMRI data to larger extent than
      regression using 24 motion parameters or spike regression. Furthermore, ICA-AROMA
      increased sensitivity to group-level activation. Our results show that ICA-AROMA
      effectively reduces motion-induced signal variations in fMRI data, is applicable
      across datasets without requiring classifier re-training, and preserves the
      temporal characteristics of the fMRI data. 

PMID- 25770992
TI  - Targeting glucose uptake with siRNA-based nanomedicine for cancer therapy.
AB  - Targeting cancer metabolism is emerging as a successful strategy for cancer
      therapy. However, most of the marketed anti-metabolism drugs in cancer therapy do
      not distinguish normal cells from cancer cells, leading to severe side effects.
      In this study, we report an effective strategy for cancer therapy through
      targeting glucose transporter 3 (GLUT3) with siRNA-based nanomedicine to
      simultaneously inhibit the self-renewal of glioma stem cells and bulk glioma
      cells in a glucose restricted tumor micro-environment. We have demonstrated that
      cationic lipid-assisted poly(ethylene glycol)-b-poly(d,l-lactide) (PEG-PLA)
      nanoparticles can efficiently deliver siRNA into U87MG and U251 glioma stem cells
      and bulk glioma cells. Nanoparticles carrying specific siRNA targeting GLUT3
      (NPsiGLUT3) were able to significantly reduce the expression of GLUT3 in glioma
      stem cells and bulk glioma cells, while GLUT3 knockdown results in obvious cell
      metabolism and proliferation inhibition, and further glioma stem cells percentage
      down-regulation. Moreover, systemic delivery of NPsiGLUT3, via intravenous
      injection, significantly inhibited tumor growth in a U87MG xenograft model, due
      to the reduced expression of GLUT3 and down-regulated stemness of glioma cells.

PMID- 25770993
TI  - A theranostic prodrug delivery system based on Pt(IV) conjugated nano-graphene
      oxide with synergistic effect to enhance the therapeutic efficacy of Pt drug.
AB  - Due to their high NIR-optical absorption and high specific surface area, graphene
      oxide and graphene oxide-based nanocomposites have great potential in both drug
      delivery and photothermal therapy. In the work reported herein we successfully
      integrate a Pt(IV) complex (c,c,t-[Pt(NH3)2Cl2(OH)2]), PEGylated nano-graphene
      oxide (PEG-NGO), and a cell apoptosis sensor into a single platform to generate a
      multifunctional nanocomposite (PEG-NGO-Pt) which shows potential for targeted
      drug delivery and combined photothermal-chemotherapy under near infrared laser
      irradiation (NIR), and real-time monitoring of its therapeutic efficacy. Non
      invasive imaging using a fluorescent probe immobilized on the GO shows an
      enhanced therapeutic effect of PEG-NGO-Pt in cancer treatment via apoptosis and
      cell death. Due to the enhanced cytotoxicity of cisplatin and the highly specific
      tumor targeting of PEG-NGO-Pt at elevated temperatures, this nanocomposite
      displays a synergistic effect in improving the therapeutic efficacy of the Pt
      drug with complete destruction of tumors, no tumor recurrence and minimal
      systemic toxicity in comparison with chemotherapy or photothermal treatment
      alone, highlighting the advantageous effects of integrating Pt(IV) with GO for
      anticancer treatment.

PMID- 25770996
TI  - Effect of mechanical stimulation on bone marrow stromal cell-seeded tendon slice
      constructs: a potential engineered tendon patch for rotator cuff repair.
AB  - Cell-based tissue engineered tendons have potential to improve clinical outcomes
      following rotator cuff repair, especially in large or massive rotator cuff tears,
      which pose a great clinical challenge. The aim of this study was to develop a
      method of constructing a functional engineered tendon patch for rotator cuff
      repair with cyclic mechanical stimulation. Decellularized tendon slices (DTSs)
      were seeded with BMSCs and subjected to cyclic stretching for 1, 3, or 7 days.
      The mechanical properties, morphologic characteristics and tendon-related gene
      expression of the constructs were investigated. Viable BMSCs were observed on the
      DTS after 7 days. BMSCs penetrated into the DTSs and formed dense cell sheets
      after 7 days of mechanical stretching. Gene expression of type I collagen,
      decorin, and tenomodulin significantly increased in cyclically stretched BMSC-DTS
      constructs compared with the unstrained control group (P < 0.05). The ultimate
      tensile strength and stiffness of the cyclically stretched tendon constructs were
      similar to the unstrained control group (P > 0.05). In conclusion, mechanical
      stimulation of BMSC-DTS constructs upregulated expression of tendon-related
      proteins, promoted cell tenogenic differentiation, facilitated cell infiltration
      and formation of cell sheets, and retained mechanical properties. The patch could
      be used as a graft to enhance the surgical repair of rotator cuff tears.

PMID- 25770995
TI  - Dual-function nanosystem for synergetic cancer chemo-/radiotherapy through ROS
      mediated signaling pathways.
AB  - Radioresistance and limitation of irradiative dosage usually lead to failure in
      depletion of hypoxic tumors. Herein we developed multifunctional mesoporous
      silica nanoparticles (MSNs) as a carrier of a novel anticancer selenoamino acid
      (selenocystine, SeC), to achieve synergistic chemo-/radiotherapy. This
      multifunctional nanosystem effectively sensitizes cancer cells to X-ray
      radiotherapy. Conjugation of TAT cell penetrating peptide and transferrin to the
      surface of MSNs significantly enhances its internalization in cancer cells
      through receptor-mediated endocytosis. SeC@MSNs-Tf/TAT significantly enhanced X
      ray-induced growth inhibition in cervical cancer cells by induction of apoptosis,
      mainly through death receptor-mediated extrinsic apoptotic pathway. Upon
      radiation, SeC@MSNs-Tf/TAT promoted intracellular ROS overproduction, which
      induced apoptotic cell death by affecting p53, AKT and MAPKs pathways.
      Furthermore, SeC@MSNs-Tf/TAT also significantly inhibited HeLa tumor growth in
      nude mice model through suppression of cell proliferation and induction of
      apoptosis. In vivo toxicity of the SeC@MSNs-Tf/TAT nanoparticles was investigated
      using the mouse model. The results of histological analysis revealed that, the
      nanoparticles did not show any obvious damage to these major organs under the
      experimental conditions, including heart, liver, spleen, lung and kidney. Taken
      together, this study demonstrates an effective and safe strategy for cancer
      targeted chemo-/radiotherapy of human cancers.

PMID- 25770994
TI  - Nanoparticle-mediated delivery of a rapidly activatable prodrug of SN-38 for
      neuroblastoma therapy.
AB  - Nanomedicine-based strategies have the potential to improve therapeutic
      performance of a wide range of anticancer agents. However, the successful
      implementation of nanoparticulate delivery systems requires the development of
      adequately sized nanocarriers delivering their therapeutic cargo to the target in
      a protected, pharmacologically active form. The present studies focused on a
      novel nanocarrier-based formulation strategy for SN-38, a topoisomerase I
      inhibitor with proven anticancer potential, whose clinical application is
      compromised by toxicity, poor stability and incompatibility with conventional
      delivery vehicles. SN-38 encapsulated in biodegradable sub-100 nm sized
      nanoparticles (NP) in the form of its rapidly activatable prodrug derivative with
      tocopherol succinate potently inhibited the growth of neuroblastoma cells in a
      dose- and exposure time-dependent manner, exhibiting a delayed response pattern
      distinct from that of free SN-38. In a xenograft model of neuroblastoma, prodrug
      loaded NP caused rapid regression of established large tumors, significantly
      delayed tumor regrowth after treatment cessation and markedly extended animal
      survival. The NP formulation strategy enabled by a reversible chemical
      modification of the drug molecule offers a viable means for SN-38 delivery
      achieving sustained intratumoral drug levels and contributing to the potency and
      extended duration of antitumor activity, both prerequisites for effective
      treatment of neuroblastoma and other cancers.

PMID- 25770997
TI  - Mussel adhesive protein provides cohesive matrix for collagen type-1alpha.
AB  - Understanding the interactions between collagen and adhesive mussel foot proteins
      (mfps) can lead to improved medical and dental adhesives, particularly for
      collagen-rich tissues. Here we investigated interactions between collagen type-1,
      the most abundant load-bearing animal protein, and mussel foot protein-3 (mfp-3)
      using a quartz crystal microbalance and surface forces apparatus (SFA). Both
      hydrophilic and hydrophobic variants of mfp-3 were exploited to probe the nature
      of the interaction between the protein and collagen. Our chief findings are: 1)
      mfp-3 is an effective chaperone for tropocollagen adsorption to TiO2 and mica
      surfaces; 2) at pH 3, collagen addition between two mfp-3 films (Wc = 5.4 +/- 0.2
      mJ/m(2)) increased their cohesion by nearly 35%; 3) oxidation of Dopa in mfp-3 by
      periodate did not abolish the adhesion between collagen and mfp-3 films, and 4)
      collagen bridging between both hydrophilic and hydrophobic mfp-3 variant films is
      equally robust, suggesting that hydrophobic interactions play a minor role.
      Extensive H-bonding, pi-cation and electrostatic interactions are more plausible
      to explain the reversible bridging of mfp-3 films by collagen.

PMID- 25770998
TI  - TiO2 nanoparticles tested in a novel screening whole human blood model of
      toxicity trigger adverse activation of the kallikrein system at low
      concentrations.
AB  - There is a compelling need to understand and assess the toxicity of industrially
      produced nanoparticles (NPs). In order to appreciate the long-term effects of
      NPs, sensitive human-based screening tests that comprehensively map the NP
      properties are needed to detect possible toxic mechanisms. Animal models can only
      be used in a limited number of test applications and are subject to ethical
      concerns, and the interpretation of experiments in animals is also distorted by
      the species differences. Here, we present a novel easy-to-perform highly
      sensitive whole-blood model using fresh non-anticoagulated human blood, which
      most justly reflects complex biological cross talks in a human system. As a
      demonstrator of the tests versatility, we evaluated the toxicity of TiO2 NPs that
      are widely used in various applications and otherwise considered to have
      relatively low toxic properties. We show that TiO2 NPs at very low concentrations
      (50 ng/mL) induce strong activation of the contact system, which in this model
      elicits thromboinflammation. These data are in line with the finding of
      components of the contact system in the protein corona of the TiO2 NPs after
      exposure to blood. The contact system activation may lead to both thrombotic
      reactions and generation of bradykinin, thereby representing fuel for chronic
      inflammation in vivo and potentially long-term risk of autoimmunity,
      arteriosclerosis and cancer. These results support the notion that this novel
      whole-blood model represents an important contribution to testing of NP toxicity.

PMID- 25770999
TI  - Role of integrin subunits in mesenchymal stem cell differentiation and osteoblast
      maturation on graphitic carbon-coated microstructured surfaces.
AB  - Surface roughness, topography, chemistry, and energy promote osteoblast
      differentiation and increase osteogenic local factor production in vitro and bone
      to-implant contact in vivo, but the mechanisms involved are not well understood.
      Knockdown of integrin heterodimer alpha2beta1 (alpha2beta1) blocks the osteogenic
      effects of the surface, suggesting signaling by this integrin homodimer is
      required. The purpose of the present study was to separate effects of surface
      chemistry and surface structure on integrin expression by coating smooth or rough
      titanium (Ti) substrates with graphitic carbon, retaining surface morphology but
      altering surface chemistry. Ti surfaces (smooth [Ra < 0.4 MUm], rough [Ra >= 3.4
      MUm]) were sputter-coated using a magnetron sputtering system with an ultrapure
      graphite target, producing a graphitic carbon thin film. Human mesenchymal stem
      cells and MG63 osteoblast-like cells had higher mRNA for integrin subunits
      alpha1, alpha2, alphav, and beta1 on rough surfaces in comparison to smooth, and
      integrin alphav on graphitic-carbon-coated rough surfaces in comparison to Ti.
      Osteogenic differentiation was greater on rough surfaces in comparison to smooth,
      regardless of chemistry. Silencing integrins beta1, alpha1, or alpha2 decreased
      osteoblast maturation on rough surfaces independent of surface chemistry.
      Silencing integrin alphav decreased maturation only on graphitic carbon-coated
      surfaces, not on Ti. These results suggest a major role of the integrin beta1
      subunit in roughness recognition, and that integrin alpha subunits play a major
      role in surface chemistry recognition.

PMID- 25771000
TI  - A recombinant slow-release PACAP-derived peptide alleviates diabetes by promoting
      both insulin secretion and actions.
AB  - Pituitary adenylate cyclase activating polypeptide (PACAP) is a neuroendocrine
      factor that activates both the receptor VPAC1 and VPAC2. Although PACAP possesses
      insulinotropic activity, its therapeutic application is limited by the extremely
      short acting half-life and the stimulatory effects on glucagon production via a
      VPAC1-dependent mechanism. Here we have generated a recombinant PACAP-derived
      peptide (named as MHDBAY) comprising a 7-mer albumin-binding peptide identified
      by phage display screening (WQRPSSW), a cleavage peptide for Factor Xa (FXa) and
      dipeptidyl peptidase IV (DPP IV), and a 31-amino acid PACAP-derived peptide
      (DBAY) that can specifically bind to the VPAC2 receptor. MHDBAY binds to albumin
      both in vitro and in animals, thereby leading to an orderly slow release of the
      active peptide DBAY via the protease cleavage. In db/db mice and New Zealand
      rabbits, the circulating half-life of MHDBAY is approximately 12.2 h, which is
      146-fold longer than DBAY (~5 min). A single injection of MHDBAY into db/db
      diabetic mice markedly increases insulin secretion, thereby leading to sustained
      alleviation of hyperglycemia. The potency and duration of MHDBAY in increasing
      insulin secretion and decreasing blood glucose levels is much greater than
      Exendin-4, an anti-diabetic drug via its insulinotropic actions. Furthermore,
      chronic administration of MHDBAY by daily injection for 8 weeks significantly
      improves both glucose and lipid profiles and also greatly increases insulin
      sensitivity in db/db mice. These findings suggest that serum albumin may act as a
      reservoir for slow-release of small bioactive peptides, and MHDBAY may represent
      a promising therapeutic peptide for diabetes.

PMID- 25771001
TI  - PEGylated-thymoquinone-nanoparticle mediated retardation of breast cancer cell
      migration by deregulation of cytoskeletal actin polymerization through miR-34a.
AB  - Thymoquinone (TQ), a major active constituent of black seeds of Nigella sativa,
      has potential medical applications including spectrum of therapeutic properties
      against different cancers. However, little is known about their effect on breast
      cancer cell migration, which is the cause of over 90% of deaths worldwide.
      Herein, we have synthesized TQ-encapsulated nanoparticles using biodegradable,
      hydrophilic polymers like polyvinylpyrrolidone (PVP) and polyethyleneglycol (PEG)
      to overcome TQ's poor aqueous solubility, thermal and light sensitivity as well
      as consequently, minimal systemic bioavailability which can greatly improve the
      cancer treatment efficiency. Sizes of synthesized TQ-Nps were found to be below
      50 nm and they were mostly spherical in shape with smooth surface texture.
      Estimation of the zeta potential also revealed that all the three TQ-Nps were
      negatively charged which also facilitated their cellular uptake. In the present
      investigation, we provide direct evidence that TQ-Nps showed more efficiency in
      killing cancer cells as well as proved to be less toxic to normal cells at a
      significantly lower dose than TQ. Interestingly, evaluation of the anti-migratory
      effect of the TQ-Nps, revealed that PEG4000-TQ-Nps showed much potent anti
      migratory properties than the other types. Further studies indicated that PEG4000
      TQ-Nps could significantly increase the expression of miR-34a through p53.
      Moreover, NPs mediated miR-34a up-regulation directly down-regulated Rac1
      expression followed by actin depolymerisation thereby disrupting the actin
      cytoskeleton which leads to significant reduction in the lamellipodia and
      filopodia formation on cell surfaces thus retarding cell migration. Considering
      the biodegradability, non-toxicity and effectivity of PEG4000-TQ-Nps against
      cancer cell migration, TQ-Nps may provide new insights into specific therapeutic
      approach for cancer treatment.

PMID- 25771002
TI  - Histopathological and biomechanical evaluation of tenocyte seeded allografts on
      rat Achilles tendon regeneration.
AB  - Tendon injuries in humans as well as in animals' veterinary medicine are
      problematic because tendon has poor regenerative capacity and complete
      regeneration of the ruptured tendon is never achieved. In the last decade there
      has been an increasing need of treatment methods with different approaches. The
      aim of the current study was to improve the regeneration process of rat Achilles
      tendon with tenocyte seeded decellularized tendon matrices. For this purpose,
      Achilles tendons were harvested, decellularized and seeded as a mixture of three
      consecutive passages of tenocytes at a density of 1 * 10(6) cells/ml.
      Specifically, cells with different passage numbers were compared with respect to
      growth characteristics, cellular senescence and collagen/tenocyte marker
      production before seeding process. The viability of reseeded tendon constructs
      was followed postoperatively up to 6 months in rat Achilles tendon by
      histopathological and biomechanical analysis. Our results suggests that tenocyte
      seeded decellularized tendon matrix can significantly improve the histological
      and biomechanical properties of tendon repair tissue without causing adverse
      immune reactions. To the best of our knowledge, this is the first long-term study
      in the literature which was accomplished to prove the use of decellularized
      matrix in a clinically relevant model of rat Achilles tendon and the method
      suggested herein might have important implications for translation into the
      clinic.

PMID- 25771003
TI  - Stimulation of angiogenesis and survival of endothelial cells by human monoclonal
      Tie2 receptor antibody.
AB  - Angiopoietin-1 (Ang1) and its endothelium-specific receptor, tyrosine kinase with
      Ig and epidermal growth factor homology domain 2 (Tie2), play critical roles in
      vascular development. Although the Ang1/Tie2 system has been considered a
      promising target for therapeutic neovascularization, several imitations of large
      scale production have hampered the development of recombinant Ang1 for
      therapeutics. In this study, we produced a fully human agonistic antibody against
      Tie2, designated 1-4h, and tested the applicability of 1-4h as an alternative to
      native Ang1 in therapeutic angiogenesis. 1-4h significantly enhanced the
      phosphorylation of Tie2 in a dose- and time-dependent manner in human Tie2
      expressing HEK293 cells and human umbilical vein endothelial cells. Moreover, 1
      4h induced the activation of Tie2-mediated intracellular signaling such as AKT,
      eNOS, MAPK, and Focal Adhesion Kinase p125(FAK). In addition, 1-4h increased the
      chemotactic motility and capillary-like tube formation of endothelial cells in
      vitro and enhanced the survival of serum-deprived endothelial cells. Taken
      together, our data clearly suggest that a human Tie2 agonistic antibody is a
      potentially useful therapeutic approach for the treatment of several ischemic
      diseases including delayed-wound healing and ischemic heart and limb diseases.

PMID- 25771004
TI  - Micron-sized iron oxide-containing particles for microRNA-targeted manipulation
      and MRI-based tracking of transplanted cells.
AB  - Particle-based delivery systems for therapeutic manipulation and tracking of
      transplanted cells by magnetic resonance imaging (MRI) are commonly based on
      nanometer-sized superparamagnetic iron oxide particles (SPIOs). Here, we present
      a proof of concept for multifunctional, silica based micron-sized iron oxide
      containing particles (sMPIO) that combine fluorescence imaging, MRI tracking, and
      on-the-spot targeting of specific microRNAs on a particle surface for therapeutic
      manipulation by RNA interference. Antisense locked nucleic acids (alpha-LNA) were
      covalently bound to the surface of silica-based, DAPI-integrated, micron-sized
      iron oxide particles (sMPIO-alpha-LNA). In vitro studies using primary human
      hepatocytes showed rapid particle uptake (4 h) that was accompanied by
      significant depletion of the targeted microRNA Let7g (80%), up-regulation of the
      target proteins Cyclin D1 and c-Myc, and specific proteome changes. sMPIO-alpha
      LNA-labeled cells were successfully detected by fluorescence imaging and could be
      visualized by MRI after intrasplenic transplantation in rats. This new
      theranostic particle provides a promising tool for cell transplantation where
      cellular imaging and microRNA-based manipulation is needed. [165].

PMID- 25771005
TI  - Functional maturation of human pluripotent stem cell derived cardiomyocytes in
      vitro--correlation between contraction force and electrophysiology.
AB  - Cardiomyocytes from human pluripotent stem cells (hPSC-CM) have many potential
      applications in disease modelling and drug target discovery but their phenotypic
      similarity to early fetal stages of cardiac development limits their
      applicability. In this study we compared contraction stresses of hPSC-CM to 2nd
      trimester human fetal derived cardiomyocytes (hFetal-CM) by imaging displacement
      of fluorescent beads by single contracting hPSC-CM, aligned by microcontact
      printing on polyacrylamide gels. hPSC-CM showed distinctly lower contraction
      stress than cardiomyocytes isolated from hFetal-CM. To improve maturation of hPSC
      CM in vitro we made use of commercial media optimized for cardiomyocyte
      maturation, which promoted significantly higher contraction stress in hPSC
      compared with hFetal-CM. Accordingly, other features of cardiomyocyte maturation
      were observed, most strikingly increased upstroke velocities and action potential
      amplitudes, lower resting membrane potentials, improved sarcomeric organization
      and alterations in cardiac-specific gene expression. Performing contraction force
      and electrophysiology measurements on individual cardiomyocytes revealed strong
      correlations between an increase in contraction force and a rise of the upstroke
      velocity and action potential amplitude and with a decrease in the resting
      membrane potential. We showed that under standard differentiation conditions hPSC
      CM display lower contractile force than primary hFetal-CM and identified
      conditions under which a commercially available culture medium could induce
      molecular, morphological and functional maturation of hPSC-CM in vitro. These
      results are an important contribution for full implementation of hPSC-CM in
      cardiac disease modelling and drug discovery.

PMID- 25771006
TI  - Sinusoidal wavy surfaces for curvature-guided migration of T lymphocytes.
AB  - Micro/nanofabricated surfaces have been widely used for the study of topography
      guided migration of cells. While the current studies mostly utilized
      micro/nanostructures containing sharp edges, internal tissues guiding migration
      of cells such as blood and lymphatic vessels, bone cavities, perivascular tracks
      have smooth microscale topographical structures. To overcome these limitations,
      we fabricated sinusoidal wavy surfaces with various wavelengths by deep X-ray
      lithography enabling precise and simultaneous control of amplitudes and
      wavelengths. Using these surfaces, we systematically studied curvature-guided
      migration of T cells. The majority of T cells migrated along the concave surfaces
      of sinusoidal wavy structures and as wavelength increased (or curvature
      decreased), preference to concave surfaces decreased. Integrin-mediated adhesion
      augmented the tendency of T cells crawling along grooves of highly curved wavy
      surfaces. To understand mechanisms of curvature-guided migration of T cells, T
      cells were treated with small molecule drugs such as blebbistatin and CK636,
      inhibiting myosin II activity and lamellipodia formation, respectively. While
      lamellipodia-inhibited T cells frequently crossed ridges, myosin II-inhibited T
      cells were mostly confined within concave surfaces. These results suggest that
      lamellipodia regulate local actin polymerization in response to surface curvature
      to maintain T cells within concave surfaces while myosin II-mediated contractile
      forces push T cells out of concave surfaces to make T cells less sensitive to
      surface curvature.

PMID- 25771007
TI  - Doxorubicin-loaded polysaccharide nanoparticles suppress the growth of murine
      colorectal carcinoma and inhibit the metastasis of murine mammary carcinoma in
      rodent models.
AB  - As a synergistic drug combination, doxorubicin-loaded cisplatin crosslinked
      polysaccharide-based nanoparticles (Dex-SA-DOX-CDDP) have demonstrated enhanced
      antitumor efficacy and reduced systemic toxicity via optimized biodistribution,
      controlled drug release, prolonged blood circulation, and improved tolerability,
      compared to the non-crosslinked nanoparticles or free doxorubicin. Herein, we
      apply the Dex-SA-DOX-CDDP nanoparticles as an efficient antitumor agent to treat
      colorectal and breast tumors in three different in vivo models, i.e.
      subcutaneously implanted colorectal carcinoma, dimethylhydrazine-induced
      autochthonous colorectal carcinoma, and metastatic mammary carcinoma, which more
      closely simulate the natural milieu of the original tumor with intact
      pathological and immunological responses. Based on the properties of this
      combination in higher tumor accumulation and penetrating efficiency, the Dex-SA
      DOX-CDDP nanoparticles significantly decreased the tumor sizes in CT26 cell line
      xenograft tumors compared to control. In addition, the affected animals' lifespan
      was significantly extended after the Dex-SA-DOX-CDDP treatment, in the
      autochthonous colon cancer model. Moreover, with the aid of iRGD, Dex-SA-DOX-CDDP
      could effectively block primary tumor growth and prevent the metastasis of 4T1
      murine mammary carcinoma. In conclusion, Dex-SA-DOX-CDDP nanoparticles remarkably
      inhibit growth of colorectal carcinoma and metastasis of mammary carcinoma in
      vivo, which provides potential application as a safe and efficient antitumor
      agent in treatment of these cancers.

PMID- 25771008
TI  - Enhanced osteointegration on tantalum-implanted polyetheretherketone surface with
      bone-like elastic modulus.
AB  - Polyetheretherketone (PEEK) possesses a similar elastic modulus as bones but yet
      suffers from bio-inertness and poor osteogenesis. In this work, tantalum ions are
      implanted energetically into PEEK by plasma immersion ion implantation (PIII) to
      form Ta2O5 nanoparticles in the near surface. Nanoindentation reveals that the
      surface elastic modulus of the Ta ion implanted PEEK is closer to that of human
      cortical bones. In vitro cell adhesion, alkaline phosphatase activity, collagen
      secretion, extracellular matrix mineralization, and real-time PCR analyses
      disclose enhanced adhesion, proliferation, and osteogenic differentiation of rat
      bone mesenchymal stem cells (bMSCs) on the Ta-PIII modified PEEK. In vivo
      evaluation of the cortico-cancellous rat femur model by means of micro-CT,
      sequential fluorescent labeling, and histological analysis after 8 weeks confirms
      significantly improved osteointegration. The bone-like elastic modulus and
      modified surface topography of the Ta-PIII modified PEEK synergistically induce
      osteogenic differentiation of bMSCs and the surface-modified materials have large
      potential in dental and orthopedic implants.

PMID- 25771009
TI  - Self-assembled PEG-IR-780-C13 micelle as a targeting, safe and highly-effective
      photothermal agent for in vivo imaging and cancer therapy.
AB  - IR-780, a representative hydrophobic near-infrared (NIR) fluorescence dye, is
      capable of fluorescently imaging and photothermal therapy in vitro and in vivo.
      However, insolubility in all pharmaceutically acceptable solvents limits its
      further biological applications. To increase solubility, we developed a novel
      self-assembled IR-780 containing micelle (PEG-IR-780-C13) based on the structural
      modification of IR-780. Briefly, a hydrophilic PEG2000 was modified on the one
      side of IR-780, and the hydrophobic carbon chain on the other side was extended
      from C3 to C16 (additional C13 carbon chain). The modification provides a better
      self-assemble capability, improved water solubility and higher stability. In
      addition, PEG-IR-780-C13 micelles are specifically targeted to the tumor after
      intravenous injection and can be used for tumor imaging. The in vitro cell
      viability assays and in vivo photothermal therapy experiments indicated that CT
      26 cells or CT-26 xenograft tumors can be effectively ablated by combining PEG-IR
      780-C13 micelles with 808 nm laser irradiation. More importantly, no significant
      toxicity can be observed after intravenous administration of the therapeutic dose
      of generated micelles. Overall, our micelles may have the least safety concern
      while showing excellent treatment efficacy, and thus may be a new photothermal
      agent potentially useful in clinical applications.

PMID- 25771010
TI  - Synthesis and application of strawberry-like Fe3O4-Au nanoparticles as CT-MR dual
      modality contrast agents in accurate detection of the progressive liver disease.
AB  - Development of non-invasive assay for the accurate diagnosis of progressive liver
      diseases (e.g., fatty liver and hepatocellular carcinoma (HCC)) is of great
      clinical significance and remains to be a big challenge. Herein, we reported the
      synthesis of strawberry-like Fe3O4-Au hybrid nanoparticles at room temperature
      that simultaneously exhibited fluorescence, enhanced X-ray attenuation, and
      magnetic properties. The results of in vitro fluorescence assay showed that the
      nanoparticles had significant photo-stability and could avoid the endosome
      degradation in cells. The in vivo imaging of normal mice demonstrated that the
      Fe3O4-Au nanoparticles provided 34.61-fold contrast enhancement under magnetic
      resonance (MR) guidance 15 min post the administration. Computed tomography (CT)
      measurements showed that the highest Hounsfield Unit (HU) was 174 at 30 min post
      the injection of Fe3O4-Au nanoparticles. In vivo performance of the Fe3O4-Au
      nanoparticles was further evaluated in rat models bearing three different liver
      diseases. For the fatty liver model, nearly homogeneous contrast enhancement was
      observed under both MR (highest contrast ratio 47.33) and CT (from 19 HU to 72
      HU) guidances without the occurrences of focal nodules or dysfunction. For the
      cirrhotic liver and HCC, pronounced enhancement under MR and CT guidance could be
      seen in liver parenchyma with highlighted lesions after Fe3O4-Au injection.
      Furthermore, pathological, hematological and biochemical analysis revealed the
      absence of acute and chronic toxicity, confirming the biocompatibility of our
      platform for in vivo applications. Collectively, These Fe3O4-Au nanoparticles
      showed great promise as a candidate for multi-modality bio-imaging.

PMID- 25771011
TI  - Nanoparticle formulations of histone deacetylase inhibitors for effective
      chemoradiotherapy in solid tumors.
AB  - Histone deacetylase inhibitors (HDACIs) represent a class of promising agents
      that can improve radiotherapy in cancer treatment. However, the full therapeutic
      potential of HDACIs as radiosensitizers has been restricted by limited efficacy
      in solid malignancies. In this study, we report the development of nanoparticle
      (NP) formulations of HDACIs that overcome these limitations, illustrating their
      utility to improve the therapeutic ratio of the clinically established first
      generation HDACI vorinostat and a novel second generation HDACI quisinostat. We
      demonstrate that NP HDACIs are potent radiosensitizers in vitro and are more
      effective as radiosensitizers than small molecule HDACIs in vivo using mouse
      xenograft models of colorectal and prostate carcinomas. We found that NP HDACIs
      enhance the response of tumor cells to radiation through the prolongation of
      gamma-H2AX foci. Our work illustrates an effective method for improving cancer
      radiotherapy treatment.

PMID- 25771012
TI  - In vitro glycation of an endothelialized and innervated tissue-engineered skin to
      screen anti-AGE molecules.
AB  - Glycation is one of the major processes responsible for skin aging through
      induction of the detrimental formation of advanced glycation end-products (AGEs).
      We developed an innovative tissue-engineered skin combining both a capillary-like
      and a nerve networks and designed a protocol to induce continuous AGEs formation
      by a treatment with glyoxal. We determined the optimal concentration of glyoxal
      to induce AGEs formation identified by carboxymethyl-lysin expression while
      keeping their toxic effects low. We showed that our tissue-engineered skin
      cultured for 44 days and treated with 200 MUm glyoxal for 31 days displayed high
      carboxymethyl-lysine expression, which induced a progressively increased
      alteration of its capillary and nerve networks between 28 and 44 days. Moreover,
      it produced an epidermal differentiation defect evidenced by the lack of loricrin
      and filaggrin expression in the epidermis. These effects were almost completely
      prevented by addition of aminoguanidine 1.5 mm, an anti-glycation compound, and
      only slightly decreased by alagebrium 500 MUm, an AGE-breaker molecule. This
      tissue-engineered skin model is the first one to combine a capillary and nerve
      network and to enable a continuous glycation over a long-term culture period. It
      is a unique tool to investigate the effects of glycation on skin and to screen
      new molecules that could prevent AGEs formation.

PMID- 25771013
TI  - Rapid determination of plasmonic nanoparticle agglomeration status in blood.
AB  - Plasmonic nanomaterials as drug delivery or bio-imaging agents are typically
      introduced to biological systems through intravenous administration. However, the
      potential for agglomeration of nanoparticles in biological systems could
      dramatically affect their pharmacokinetic profile and toxic potential.
      Development of rapid screening methods to evaluate agglomeration is urgently
      needed to monitor the physical nature of nanoparticles as they are introduced
      into blood. Here, we establish novel methods using darkfield microscopy with
      hyperspectral detection (hsDFM), single particle inductively-coupled plasma mass
      spectrometry (spICP-MS), and confocal Raman microscopy (cRM) to discriminate gold
      nanoparticles (AuNPs) and their agglomerates in blood. Rich information about
      nanoparticle agglomeration in situ is provided by hsDFM monitoring of the plasmon
      resonance of primary nanoparticles and their agglomerates in whole blood; cRM is
      an effective complement to hsDFM to detect AuNP agglomerates in minimally
      manipulated samples. The AuNPs and the particle agglomerates were further
      distinguished in blood for the first time by quantification of particle mass
      using spICP-MS with excellent sensitivity and specificity. Furthermore, the
      agglomeration status of synthesized and commercial NPs incubated in blood was
      successfully assessed using the developed methods. Together, these complementary
      methods enable rapid determination of the agglomeration status of plasmonic
      nanomaterials in biological systems, specifically blood. 

PMID- 25771014
TI  - Injectable glycopolypeptide hydrogels as biomimetic scaffolds for cartilage
      tissue engineering.
AB  - Glycopolypeptides are an emerging class of bioinspired polymers that mimic
      naturally occurring glycopeptides or glycoproteins, and therefore are expected to
      exhibit great potential for biomedical applications. In this study, a
      glycopolypeptide was synthesized by conjugation of poly(gamma-propargyl-l
      glutamate) (PPLG) with azido-modified mannose and 3-(4-hydroxyphenyl) propanamide
      (HPPA), via click chemistry. Injectable hydrogels based on the glycopolypeptide
      were developed through enzymatic crosslinking reaction in the presence of
      horseradish peroxidase (HRP) and hydrogen peroxide (H2O2). The physicochemical
      properties of the hydrogels, such as gelation time, storage modulus, swelling and
      degradation time, could be controlled by varying the concentrations of HRP and
      H2O2. The glycopolypetide copolymer as well as the extracts of the
      glycopolypetide hydrogels displayed good cytocompatibility in vitro. After
      subcutaneous injection into rats, the glycopolypeptide hydrogels were rapidly
      formed in situ, and exhibited acceptable biocompatibility accompanying the
      degradation of the hydrogels in vivo. The rabbit chondrocytes inside the
      glycopolypeptide hydrogels showed spherical morphology with high viability during
      the incubation period of 3 weeks in vitro, and exhibited a higher proliferation
      rate than within the hydrogel counterparts of PPLG grafted with 2-(2-(2
      methoxyethoxy)ethoxy)ethane (MEO3) and HPPA. Biochemical analysis demonstrated
      that the production of glycosaminoglycans (GAG) and type II collagen were
      significantly enhanced after incubation for 2 and 3 weeks in vitro. Moreover, the
      chondrocyte-containing glycopolypeptide hydrogels in subcutaneous model of nude
      mice maintained chondrocyte phenotype and produced the cartilaginous specific
      matrix. These results indicated that the biomimetic glycopolypeptide-based
      hydrogels hold potential as three-dimensional scaffolds for cartilage tissue
      engineering.

PMID- 25771015
TI  - A plug-and-play ratiometric pH-sensing nanoprobe for high-throughput
      investigation of endosomal escape.
AB  - An important aspect in the design of nanomaterials for delivery is an
      understanding of its uptake and ultimate release to the cytosol of target cells.
      Real-time chemical sensing using a nanoparticle-based platform affords exquisite
      insight into the trafficking of materials and their cargo into cells. This
      versatile and tunable technology provides a powerful tool to probe the mechanism
      of cellular entry and cytosolic delivery of a variety of materials, allowing for
      a simple and convenient means to screen materials towards efficient delivery of
      therapeutics such as nucleic acids.

PMID- 25771016
TI  - Biomimetic collagen I and IV double layer Langmuir-Schaefer films as
      microenvironment for human pluripotent stem cell derived retinal pigment
      epithelial cells.
AB  - The environmental cues received by the cells from synthetic substrates in vitro
      are very different from those they receive in vivo. In this study, we applied the
      Langmuir-Schaefer (LS) deposition, a variant of Langmuir-Blodgett technique, to
      fabricate a biomimetic microenvironment mimicking the structure and organization
      of native Bruch's membrane for the production of the functional human embryonic
      stem cell derived retinal pigment epithelial (hESC-RPE) cells. Surface pressure
      area isotherms were measured simultaneously with Brewster angle microscopy to
      investigate the self-assembly of human collagens type I and IV on air-subphase
      interface. Furthermore, the structure of the prepared collagen LS films was
      characterized with scanning electron microscopy, atomic force microscopy, surface
      plasmon resonance measurements and immunofluorescent staining. The integrity of
      hESC-RPE on double layer LS films was investigated by measuring transepithelial
      resistance and permeability of small molecular weight substance. Maturation and
      functionality of hESC-RPE cells on double layer collagen LS films was further
      assessed by RPE-specific gene and protein expression, growth factor secretion,
      and phagocytic activity. Here, we demonstrated that the prepared collagen LS
      films have layered structure with oriented fibers corresponding to architecture
      of the uppermost layers of Bruch's membrane and result in increased barrier
      properties and functionality of hESC-RPE cells as compared to the commonly used
      dip-coated controls.

PMID- 25771017
TI  - Phagocytosis of immunoglobulin-coated emulsion droplets.
AB  - Phagocytosis by macrophages represents a fundamental process essential for both
      immunity and tissue homeostasis. The size of targets to be eliminated ranges from
      small particles as bacteria to large objects as cancerous or senescent cells.
      Most of our current quantitative knowledge on phagocytosis is based on the use of
      solid polymer microparticles as model targets that are well adapted to the study
      of phagocytosis mechanisms that do not involve any lateral mobility of the
      ligands, despite the relevance of this parameter in the immunological context.
      Herein we designed monodisperse, IgG-coated emulsion droplets that are
      efficiently and specifically internalized by macrophages through in-vitro
      FcgammaR-mediated phagocytosis. We show that, contrary to solid polymeric beads,
      droplet uptake is efficient even for low IgG densities, and is accompagnied by
      the clustering of the opsonins in the zone of contact with the macrophage during
      the adhesion step. Beyond the sole interest in the design of the material, our
      results suggest that lateral mobility of proteins at the interface of a target
      greatly enhances the phagocytic uptake. 

PMID- 25771018
TI  - High-throughput screening with nanoimprinting 3D culture for efficient drug
      development by mimicking the tumor environment.
AB  - Anti-cancer drug development typically utilizes high-throughput screening with
      two-dimensional (2D) cell culture. However, 2D culture induces cellular
      characteristics different from tumors in vivo, resulting in inefficient drug
      development. Here, we report an innovative high-throughput screening system using
      nanoimprinting 3D culture to simulate in vivo conditions, thereby facilitating
      efficient drug development. We demonstrated that cell line-based nanoimprinting
      3D screening can more efficiently select drugs that effectively inhibit cancer
      growth in vivo as compared to 2D culture. Metabolic responses after treatment
      were assessed using positron emission tomography (PET) probes, and revealed
      similar characteristics between the 3D spheroids and in vivo tumors. Further, we
      developed an advanced method to adopt cancer cells from patient tumor tissues for
      high-throughput drug screening with nanoimprinting 3D culture, which we termed
      Cancer tissue-Originated Uniformed Spheroid Assay (COUSA). This system identified
      drugs that were effective in xenografts of the original patient tumors.
      Nanoimprinting 3D spheroids showed low permeability and formation of hypoxic
      regions inside, similar to in vivo tumors. Collectively, the nanoimprinting 3D
      culture provides easy-handling high-throughput drug screening system, which
      allows for efficient drug development by mimicking the tumor environment. The
      COUSA system could be a useful platform for drug development with patient cancer
      cells.

PMID- 25771019
TI  - Efficient in vitro and in vivo pulmonary delivery of nucleic acid by carbon dot
      based nanocarriers.
AB  - Cationic carbon dots were fabricated by pyrolysis of citric acid and bPEI25k
      under microwave radiation. Various nanoparticles were produced in a 20-30% yield
      through straightforward modifications of the reaction parameters (stoichiometry
      of the reactants and energy supply regime). Particular attention was paid to the
      purification of the reaction products to ensure satisfactory elimination of the
      residual starting polyamine. Intrinsic properties of the particles (size, surface
      charge, photoluminescence and quantum yield) were measured and their ability to
      form stable complexes with nucleic acid was determined. Their potential to
      deliver plasmid DNA or small interfering RNA to various cell lines was
      investigated and compared to that of bPEI25k. The pDNA in vitro transfection
      efficiency of these carbon dots was similar to that of the parent PEI, as was
      their cytotoxicity. The higher cytotoxicity of bPEI25k/siRNA complexes when
      compared to that of the CD/siRNA complexes however had marked consequences on the
      gene silencing efficiency of the two carriers. These results are not fully
      consistent with those in some earlier reports on similar nanoparticles, revealing
      that toxicity of the carbon dots strongly depends on their protocol of
      fabrication. Finally, these carriers were evaluated for in vivo gene delivery
      through the non-invasive pulmonary route in mice. High transgene expression was
      obtained in the lung that was similar to that obtained with the golden standard
      formulation GL67A, but was associated with significantly lower toxicity. Post
      functionalization of these carbon dots with PEG or targeting moieties should
      significantly broaden their scope and practical implications in improving their
      in vivo transfection efficiency and biocompatibility.

PMID- 25771020
TI  - Capture of endothelial cells under flow using immobilized vascular endothelial
      growth factor.
AB  - We demonstrate the ability of immobilized vascular endothelial growth factor
      (VEGF) to capture endothelial cells (EC) with high specificity under fluid flow.
      To this end, we engineered a surface consisting of heparin bound to poly-l-lysine
      to permit immobilization of VEGF through the C-terminal heparin-binding domain.
      The immobilized growth factor retained its biological activity as shown by
      proliferation of EC and prolonged activation of KDR signaling. Using a
      microfluidic device we assessed the ability to capture EC under a range of shear
      stresses from low (0.5 dyne/cm(2)) to physiological (15 dyne/cm(2)). Capture was
      significant for all shear stresses tested. Immobilized VEGF was highly selective
      for EC as evidenced by significant capture of human umbilical vein and ovine
      pulmonary artery EC but no capture of human dermal fibroblasts, human hair
      follicle derived mesenchymal stem cells, or mouse fibroblasts. Further, VEGF
      could capture EC from mixtures with non-EC under low and high shear conditions as
      well as from complex fluids like whole human blood under high shear. Our findings
      may have far reaching implications, as they suggest that VEGF could be used to
      promote endothelialization of vascular grafts or neovascularization of implanted
      tissues by rare but continuously circulating EC.

PMID- 25771022
TI  - Reflections on HIS 2014: In praise of enthusiasts.
AB  - Medical conferences have had a bad press recently. They have been accused of
      leaving nothing but indifferent research and an enormous carbon footprint. They
      are also likely to contribute to 'intervention bias' in healthcare, in that the
      speakers tend to be selected from among the more enthusiastic interventionists
      and charismatic optimists. But this weakness is arguably also an important
      strength, for they can be the vehicle by which participants are inspired to
      innovate and evaluate. It is difficult to predict the outcome of interventions
      aimed at prevention and control of infection because they involve interactions
      between people and complex systems, not to mention the invisible agents of
      infection. Progress therefore depends largely on the empirical approach - trial
      and error. In this context we need both enthusiasts to inspire trial and sceptics
      to expose error. Conferences deserve support for encouraging debate between
      enthusiasts and sceptics, for providing a forum for cross-fertilization between
      sub-specialties, and for inspiring trainees as well as practitioners. The papers
      presented in this issue of JHI illustrate the wide range of contemporary
      challenges in healthcare-associated infection, and summarize the 'state of the
      art' of infection prevention and control. 

PMID- 25771021
TI  - Tissue engineering a surrogate niche for metastatic cancer cells.
AB  - In breast and prostate cancer patients, the bone marrow is a preferred site of
      metastasis. We hypothesized that we could use tissue-engineering strategies to
      lure metastasizing cancer cells to tissue-engineered bone marrow. First, we
      generated highly porous 3D silk scaffolds that were biocompatible and amenable to
      bone morphogenetic protein 2 functionalization. Control and functionalized silk
      scaffolds were subcutaneously implanted in mice and bone marrow development was
      followed. Only functionalized scaffolds developed cancellous bone and red bone
      marrow, which appeared as early as two weeks post-implantation and further
      developed over the 16-week study period. This tissue-engineered bone marrow
      microenvironment could be readily manipulated in situ to understand the biology
      of bone metastasis. To test the ability of functionalized scaffolds to serve as a
      surrogate niche for metastasis, human breast cancer cells were injected into the
      mammary fat pads of mice. The treatment of animals with scaffolds had no
      significant effect on primary tumor growth. However, extensive metastasis was
      observed in functionalized scaffolds, and the highest levels for scaffolds that
      were in situ manipulated with receptor activator of nuclear factor kappa-B ligand
      (RANKL). We also applied this tissue-engineered bone marrow model in a prostate
      cancer and experimental metastasis setting. In summary, we were able to use
      tissue-engineered bone marrow to serve as a target or "trap" for metastasizing
      cancer cells.

PMID- 25771024
TI  - Resistant hypertension: a volemic or nervous matter?

PMID- 25771023
TI  - Outpatient blood pressure monitoring using bi-directional text messaging.
AB  - To diagnose hypertension, multiple blood pressure (BP) measurements are
      recommended. We randomized patients into three groups: EMR-only (patients
      recorded BP measurements in an electronic medical record [EMR] web portal), EMR +
      reminders (patients were sent text message reminders to record their BP
      measurements in the EMR), and bi-directional text messaging (patients were sent a
      text message asking them to respond with their current BP). Subjects were asked
      to complete 14 measurements. Automated messages were sent to each patient in the
      bi-directional text messaging and EMR + reminder groups twice daily. Among 121
      patients, those in the bi-directional text messaging group reported the full 14
      measurements more often than both the EMR-only group (P < .001) and the EMR +
      reminders group (P = .038). Also, the EMR + reminders group outperformed the EMR
      only group (P < .001). Bi-directional automated text messaging is an effective
      way to gather patient BP data. Text-message-based reminders alone are an
      effective way to encourage patients to record BP measurements.

PMID- 25771025
TI  - Arthrodesis of thumb interphalangeal and finger distal interphalangeal joints
      using the intramedullary X-Fuse((r)) implant: Retrospective analysis of 38 cases.
AB  - Various indications exist for thumb interphalangeal and finger distal
      interphalangeal arthrodesis. Various fixation techniques (compression screws,
      tension band wiring, K-wires) have been described with fusion rates varying
      between 80 and 100%. The objective of this study was to evaluate the outcomes of
      interphalangeal arthrodesis using the X-Fuse((r)) intramedullary implant in terms
      of fusion rate and fusion position. A continuous series of 38 arthrodesis
      procedures was reviewed retrospectively to determine the fusion rate and evaluate
      complications linked to this fixation technique. The position of the fused joint
      was compared to that obtained at the end of the procedure so as to evaluate the
      reliability of implant placement. The fusion rate was 94.8%; two arthrodeses had
      to be redone with satisfactory results. A moderate change of less than 10 degrees
      in the arthrodesis position between the immediate postoperative period and fusion
      was observed in the frontal and sagittal planes that had no clinical
      consequences. The fusion rate reported here is similar to the best rates
      published with other fusion techniques, and few complications occurred. Use of
      this intramedullary implant seems to be a viable alternative to the other
      techniques.

PMID- 25771026
TI  - Cardiovascular demands of deer retrieval methods.
AB  - OBJECTIVE: The purpose of this study was to compare the cardiovascular (CV)
      demands of 2 deer retrieval methods. METHODS: Twelve male participants (weight
      86+/-24 kg, age 21+/-1 years) performed a maximum treadmill test on day 1 to
      determine baseline fitness levels. On day 2, all participants first towed, then
      dragged a 45-kg simulated deer carcass for 457 m at a self-selected pace. The tow
      condition utilized a shoulder harness system with a 2-m strap connecting the
      harness to the carcass, allowing the participant to walk upright as he towed the
      load. The dragging condition required the participants to flex their trunk, grasp
      the legs of the deer with both hands, and drag the carcass the length of the
      course. Heart rate and oxygen consumption (VO2) from each trial were measured by
      indirect calorimetry. RESULTS: The CV responses of towing were significantly less
      compared with those of dragging for VO2 peak (P=.001), peak heart rate (P=.003),
      average heart rate (P=.028), and rating of perceived exertion (P<.001). No
      significant differences were observed for average VO2 (P=.91) or time to
      completion (P=.27). CONCLUSIONS: The results of this study suggest towing a deer
      with a shoulder harness results in significant reductions in CV demand and lower
      perceived exertion compared with traditional deer dragging techniques. Deer
      hunters who are deconditioned or have CV risk factors are strongly encouraged to
      consider deer retrieval methods utilizing a shoulder harness and tow rope to
      mitigate the increased demands commonly found with traditional retrieval methods.

PMID- 25771027
TI  - Which Improvised Tourniquet Windlasses Work Well and Which Ones Won't?
AB  - OBJECTIVE: Improvised tourniquets in first aid are recommended when no
      scientifically designed tourniquet is available. Windlasses for mechanical
      advantage can be a stick or pencil and can be used singly or multiply in
      tightening a tourniquet band, but currently there is an absence of empiric
      knowledge of how well such windlasses work. The purpose of the present study was
      to determine the performance of improvised tourniquets in their use by the type
      and number of windlasses to improve tourniquet practice. METHODS: A simulated Leg
      Tourniquet Trainer was used as a manikin thigh to test the effectiveness of
      improvised tourniquets of a band-and-windlass design. Two users made 20 tests
      each with 3 types of windlasses. Tests started with 1 representative of a given
      type (eg, 1 pencil), then continued with increasing numbers of each windlass type
      until the user reached 100% effectiveness as determined by cessation of simulated
      blood flow. Windlass types included chopsticks, pencils, and craft sticks.
      RESULTS: Effectiveness percentages in stopping bleeding were associated inversely
      with breakage percentages. Pulse stoppage percentages were associated inversely
      with breakage. The windlass turn numbers, time to stop bleeding, the number of
      windlasses, and the under-tourniquet pressure were associated inversely with
      breakage. The windlass type was associated with breakage; at 2 windlasses, only
      chopsticks were without breakage. Of those windlass types that broke, 20.7% were
      chopsticks, 26.1% were pencils, and 53.2% were craft sticks. CONCLUSIONS: A pair
      of chopsticks as an improvised tourniquet windlass worked better than pencils or
      craft sticks.

PMID- 25771028
TI  - Wilderness image.

PMID- 25771029
TI  - A Case Study: Rare Lepiota brunneoincarnata Poisoning.
AB  - Amatoxin poisoning from the genus Lepiota may have a deadly outcome, although
      this is not seen as often as it is from the genus Amanita. In this report, we
      present a patient who was poisoned by a sublethal dose of Lepiota
      brunneoincarnata mushrooms. The patient was hospitalized 12 hours after eating
      the mushrooms. The patient's transaminase levels increased dramatically starting
      on day 4. Aspartate transaminase peaked at 78 hours. Starting at 1265 IU/L,
      alanine transaminase peaked at 90 hours at 5124 IU/L. The patient was discharged
      on day 8 to outpatient care, and his transaminase levels returned to normal
      ranges in the subsequent days. A toxin analysis was carried out on the mushrooms
      that the patient claimed to have eaten. Using reversed-phase high-performance
      liquid chromatography analysis, an uptake of approximately 19.9 mg of amatoxin
      from nearly 30 g of mushrooms was calculated. This consisted of 10.59 mg of alpha
      amanitin, 9.18 mg of beta-amanitin, and 0.16 mg of gamma-amanitin. In conclusion,
      we present a patient from Turkey who was poisoned by L. brunneoincarnata
      mushrooms. 

PMID- 25771030
TI  - Novel application of chemical cold packs for treatment of exercise-induced
      hyperthermia: a randomized controlled trial.
AB  - OBJECTIVE: Heat-related illness is a common disease with significant morbidity
      and mortality. Despite no proven efficacy, application of chemical cold packs
      (CCP) to the skin overlying the large vessels of the neck, groin, and axillae is
      a traditional recommended cooling modality. The study objective was to compare
      the cooling rates of CCP applied to these traditional areas vs the glabrous skin
      surfaces of the cheeks, palms, and soles in exercise-induced hyperthermia.
      METHODS: Ten healthy adult male volunteers walked on a treadmill in a heated room
      (40 degrees +/-0.5 degrees C) while wearing insulated military overgarments until
      their esophageal temperatures (Tes) reached 39.2 degrees C. Each participant had
      three heat stress trials on separate days: no treatment followed by randomly
      ordered traditional (neck, groin, and axillae) cooling and glabrous skin cooling.
      RESULTS: With no treatment, Tes remained stable after the first 5 minutes of the
      heat trial (DeltaTes=0.12 degrees +/-0.07 degrees C/10 min). Traditional cooling
      followed a linear decline (DeltaTes=0.17 degrees +/-0.04 degrees C/10 min;
      P<.001). Glabrous cooling enhanced the treatment effect by a steeper decline
      (DeltaTes=0.30 degrees +/-0.06 degrees C/10 min; P<.001), significantly different
      from traditional cooling by 2-way analysis of variance (P<.001). CONCLUSIONS:
      Application of CCP to glabrous skin surfaces was more effective for treating
      exercise-induced heat stress than the traditional CCP cooling intervention. This
      novel cooling technique may be beneficial as an adjunctive treatment for heat
      related illness in the prehospital environment.

PMID- 25771031
TI  - Negative predictive value of excluding an embedded snake foreign body by
      ultrasonography.
AB  - OBJECTIVE: Numerous reputable sources for healthcare providers advocate routine
      imaging to rule out an embedded tooth or fang after a snake bite. The objective
      of this study was to determine whether these foreign bodies can be reliably
      excluded by bedside ultrasonography. METHODS: All emergency medicine (EM)
      residents and faculty at a single institution were invited to participate. Two
      sets of 5 ultrasound gel phantoms were prepared using a method previously
      validated to have the same density as human tissue. In the first set of 5
      phantoms, 1 snake fang was embedded to simulate a retained foreign body.
      Similarly, in the second set of 5 phantoms, 1 snake tooth was also embedded.
      Participants were asked to identify the presence or absence of a foreign body in
      each phantom using bedside ultrasonography. Year of training and confidence in
      excluding a snake foreign body were also recorded. RESULTS: Each participant
      (n=27) performed ultrasound imaging on 10 phantoms for a total of 270 samples.
      Range of experience included postgraduate year 1 (25.9%), postgraduate year 2
      (29.6%), postgraduate year 3 (33.3%), and graduates of EM residency (11.1%). The
      sensitivity and negative predictive value for ruling out an embedded fang was
      92.6% and 98.1%, respectively. The sensitivity and negative predictive value for
      ruling out an embedded tooth was 77.8% and 93.7%, respectively. Among all the
      phantoms, there was a sensitivity of 85.2% and a negative predictive value of
      96%. CONCLUSION: Bedside ultrasonography performed by an EM physician is a
      feasible option to rule out embedded foreign bodies after a snake bite if imaging
      is warranted.

PMID- 25771032
TI  - Identification of 6-benzyloxysalicylates as a novel class of inhibitors of 15
      lipoxygenase-1.
AB  - Lipoxygenases metabolize polyunsaturated fatty acids into signalling molecules
      such as leukotrienes and lipoxins. 15-lipoxygenase-1 (15-LOX-1) is an important
      mammalian lipoxygenase and plays a crucial regulatory role in several respiratory
      diseases such as asthma, COPD and chronic bronchitis. Novel potent and selective
      inhibitors of 15-LOX-1 are required to explore the role of this enzyme in drug
      discovery. In this study we describe structure activity relationships for 6
      benzyloxysalicylates as inhibitors of human 15-LOX-1. Kinetic analysis suggests
      competitive inhibition and the binding model of these compounds can be
      rationalized using molecular modelling studies. The most potent derivative 37a
      shows a Ki value of 1.7 MUM. These structure activity relationships provide a
      basis to design improved inhibitors and to explore 15-LOX-1 as a drug target.

PMID- 25771033
TI  - Synthesis and in vitro and in vivo biological evaluation of substituted
      nitroquinoxalin-2-ones and 2,3-diones as novel trichomonacidal agents.
AB  - Two series of ten novel 7-nitroquinoxalin-2-ones and ten 6-nitroquinoxaline-2,3
      diones with diverse substituents at positions 1 and 4 were synthesized and
      evaluated against the sexually transmitted parasite Trichomonas vaginalis.
      Furthermore, diverse molecular and drug-likeness properties were analyzed to
      predict the oral bioavailability following the Lipinski's "rule of five". 7
      Nitroquinoxalin-2-one derivatives displayed moderate to high in vitro activity
      while the efficiency of most nitroquinoxaline-2,3-diones was rather low; both
      kinds of compounds did not show cytotoxic effects in mammalian cells. 7-Nitro-4
      (3-piperidinopropyl)quinoxalin-2-one 9 achieved the highest trichomonacidal
      activity (IC50 = 18.26 MUM) and was subsequently assayed in vivo in a murine
      model of trichomonosis. A 46.13% and a 50.70% reduction of pathogenic injuries
      were observed in the experimental groups treated orally during 7 days with 50
      mg/kg and 100 mg/kg doses. The results obtained in the biological assays against
      T. vaginalis indicate that compounds with omega-(dialkylamino)alkyl substituents
      and a keto group at positions 4 and 2 of quinoxaline ring, respectively, provide
      interesting structural cores to develop novel prototypes to enhance the
      nitroquinoxalinones activity as trichomonacidal agents with interesting ADME
      properties according to virtual screening analysis.

PMID- 25771034
TI  - Design, synthesis and biological evaluation of novel sesquiterpene mustards as
      potential anticancer agents.
AB  - Several novel series of sesquiterpene mustards (SMs) bearing nitrogen mustard and
      glutathione (GSH)-reactive alpha-methylene-gamma-butyrolactone groups were
      successfully prepared for the first time and showed excellent antiproliferative
      activities in vitro. Among them, compounds 2e and 2g displayed the highest
      antiproliferative properties with IC50 values ranging from 2.5 to 8.7 MUM. The
      selectivity of these two compounds was evaluated by SRB method against human
      cancer and normal hepatic cells (HepG2 and L02). The induction of apoptosis and
      effects on the cell cycle distribution with compounds 2e and 2g were investigated
      by Hoechst 33,258 staining and flow cytometry, which exhibited that they could
      induce selective cell apoptosis and cell cycle arrest in HepG2 and L02 cells. In
      addition, further investigation showed that compounds 2e and 2g could obviously
      inhibit the proliferation of HepG2 cells by inducing significant DNA cross
      linking and depleting GSH in cell media. The good cytotoxicity and selectivity of
      compounds 2e and 2g pointed them as promising leads for anticancer drug design.

PMID- 25771035
TI  - Preoperative nerve imaging using computed tomography in patients with heterotopic
      ossification of the elbow.
AB  - HYPOTHESIS: This study evaluated the usefulness of computed tomography (CT)
      imaging for preoperative planning of heterotopic ossification (HO) excision,
      specifically the spatial relationship between HO and radial and median nerves.
      Our hypotheses were that CT imaging of the elbow can be used (1) to trace the
      paths of the radial and median nerves, (2) to distinguish the nerves from the
      heterotopic bone, and (3) to precisely measure distances from the respective
      nerve to the most clinically relevant HO. MATERIALS AND METHODS: Patients who had
      HO removed from the elbow were reviewed retrospectively. On the basis of
      preoperative CT scans, 22 were identified as likely having HO along the pathway
      of the radial or median nerve. These cases were independently evaluated by 4
      observers, who answered these questions: (1) Can the location of the nerve be
      adequately seen on sequential images to permit tracing of its path for surgical
      planning? (2) Can the nerve be distinguished from the HO accurately enough to
      permit measurement of its distance from the bone? Each observer also measured the
      shortest distance between nerves and the HO. RESULTS: Overall utility of the CT
      images for visualizing the nerves was high. The radial nerve was more readily
      distinguished from the HO (21 of 22 cases) than the median nerve (17 of 22
      cases). The distance measured from HO was less for the radial nerve (3 mm) than
      for the median nerve (9 mm). CONCLUSION: This study demonstrates the usefulness
      of CT imaging to determine the paths of the radial and median nerves and their
      spatial relationship to HO at the elbow.

PMID- 25771036
TI  - Assessment of health status and program performance in patients on long-term
      oxygen therapy.
AB  - BACKGROUND: Despite well established clinical guidelines, performance of long
      term oxygen therapy (LTOT) programs shows marked variability among territories.
      The current study assessed the LTOT program and the health status of patients on
      LTOT prior to the deployment of community-based integrated care in an urban
      health district of Barcelona (Spain). AIMS: To assess: i) the LTOT program and
      health status of the patients on LTOT in the health district; ii) their frailty
      profile; and, iii) the requirements for effective deployment of integrated care
      services for these patients. METHODS: Cross-sectional observational study design
      including all patients (n = 406) on LTOT living in the health district. Health
      status, frailty, arterial blood gases, forced spirometry and hand-grip muscle
      strength were measured. Network analysis of frailty was carried out. RESULTS:
      Adequacy of LTOT prescription (n = 362): 47% and 31% of the patients had PaO2 <=
      60 mmHg and <=55 mmHg, respectively. Adherence to LTOT: 31% of all patients used
      LTOT >=15 h/d; this figure increased to 67% in those with PaO2<=60 mmHg.
      Assessment of frailty: Overall, LTOT patients presented moderate to severe
      frailty. Care complexity was observed in 42% of the patients. CONCLUSIONS:
      Adequacy and adherence to LTOT was poor and many patients were frail and complex.
      The outcomes of the network analysis may contribute to enhance assessment of
      frailty in LTOT patients. These observations suggest that an integrated care
      strategy has the potential to improve the health outcomes of these patients.

PMID- 25771037
TI  - Assessment of the factors affecting the failure to use inhaler devices before and
      after training.
AB  - BACKGROUND: Inhaler devices used for the treatment of chronic respiratory
      diseases are frequently incorrectly used by the patients. The effects of training
      on the correct use of these devices are unquestionable. However, despite the
      training provided on the correct technique of using the inhaler device, some
      patients still continue using the device incorrectly. The aims of the present
      study are to determine the rate of incorrect use of the inhaler devices, assess
      the parameters that affect the incorrect use, demonstrate the contribution of
      training, and determine the characteristics of the patients who use the devices
      incorrectly despite training. METHODS: 342 consecutive patients were included in
      the study. The patients' ability to use the devices correctly was scored before
      and after face-to-face trainings. The parameters affecting incorrect use, the
      impact of training, and characteristics of the patients who continued the
      incorrect usage after training were evaluated. RESULTS: The rate of correct usage
      was 58.9% for dry powder inhalers (DPI) and 31.1% for pressurized metered dose
      inhalers (pMDI) before the training. The parameters affecting correct usage were
      educational status, gender, living in rural areas, duration of disease, and being
      diagnosed and followed-up by a chest diseases specialist. The rate of correct
      usage increased to 92.6% for DPI and 45.2% for pMDI after the training. The
      factors affecting continued incorrect usage after standard training were old age
      and the type of the pMDI device. CONCLUSIONS: The technique for using the inhaler
      device should be described to the patients in a face-to-face session by the
      prescribing physician. Device selection should be done on a "trial" basis and it
      should be considered that particularly older patients and those using pMDIs
      continue using the devices incorrectly despite training; hence, alternative
      treatment options should be reviewed for these patients.

PMID- 25771039
TI  - Menopausal hormone therapy and ovarian cancer: Putting risk into perspective.

PMID- 25771038
TI  - Protein-dependent regulation of feeding and metabolism.
AB  - Free-feeding animals often face complex nutritional choices that require the
      balancing of competing nutrients, but the mechanisms driving macronutrient
      specific food intake are poorly defined. A large number of behavioral studies
      indicate that both the quantity and quality of dietary protein can markedly
      influence food intake and metabolism, and that dietary protein intake may be
      prioritized over energy intake. This review focuses on recent progress in
      defining the mechanisms underlying protein-specific feeding. Considering the
      evidence that protein powerfully regulates both food intake and metabolism,
      uncovering these protein-specific mechanisms may reveal new molecular targets for
      the treatment of obesity and diabetes while also offering a more complete
      understanding of how dietary factors shape both food intake and food choice. 

PMID- 25771040
TI  - A comparison of dance interventions in people with Parkinson disease and older
      adults.
AB  - It is important for our aging population to remain active, particularly those
      with chronic diseases, like Parkinson disease (PD), which limit mobility. Recent
      studies in older adults and people with PD suggest dance interventions provide
      various motor benefits. The literature for dance in PD is growing, but many
      knowledge gaps remain, relative to what is known in older adults. The purpose of
      this review is to: (1) detail results of dance intervention studies in older
      adults and in PD, (2) describe limitations of dance research in these
      populations, and (3) identify directions for future study. Generally, a wide
      variety of dance styles have been investigated in older adults, while a more
      limited subset has been evaluated in PD. Measures vary widely across studies and
      a lack of standardized outcomes measures hinders cross-studies comparisons.
      Compared to the dance literature in older adults, there is a notable absence of
      evidence in the PD literature in outcome domains related to cardiovascular
      health, muscle strength, body composition, flexibility, and proprioception. As a
      whole, the dance literature supports substantial and wide-ranging benefits in
      both populations, but additional effort should be dedicated to well-designed
      comparative studies using standardized outcome measures to identify optimal
      treatment programs. 

PMID- 25771042
TI  - The aging population: imperative to uncouple sex and gender to establish "gender
      equal" health care.
AB  - AIM: The transgender community has long been marginalized in society. As the
      world's population ages, gender-unbiased health services for this growing
      population, with age-related chronic illnesses, will be essential. To optimally
      eliminate hurdles that trans individuals often confront when requesting services,
      it appears judicious to eliminate the strict and antiquated definition of what
      constitutes "normal" female and "normal" male. METHODS: A review of literature on
      transgender medicine on PubMed over the last five years was conducted. RESULTS:
      Existing statistics indicate that unacceptable bias and discrimination are
      occurring, making trans patients less likely to seek care. There are emerging
      initiatives that address the transgender and gender non-conforming population.
      Ongoing needs include defining what constitutes "gender equal," understanding the
      continuum of gender identity, and establishing and implementing guidelines for
      gender equal counseling and care. CONCLUSIONS: With the routine practice of
      defining sex at birth and equating sex with gender in the health care setting,
      the transgender patient encounters multiple barriers to accessing and acquiring
      health care services. These strict gender labels appear to preclude the
      institution of gender equal care. Care templates on gender equal patient
      encounters should be implemented to better address transgender health needs in a
      non-biased manner.

PMID- 25771041
TI  - Prasterone has parallel beneficial effects on the main symptoms of vulvovaginal
      atrophy: 52-week open-label study.
AB  - OBJECTIVE: An objective was to analyze the time course of efficacy of daily
      intravaginal administration of 0.5% (6.5mg) DHEA (prasterone) for 52 weeks on the
      moderate to severe (MS) symptoms and signs of vulvovaginal atrophy (VVA). METHOD:
      Five hundred twenty-one postmenopausal women were enrolled and received daily
      intravaginal administration of 0.5% DHEA in an open-label phase III study. The
      severity of the VVA symptoms examined in detail in the different groups. RESULTS:
      A parallel improvement of pain at sexual activity was observed in women who had
      moderate to severe (MS) dyspareunia as their most bothersome symptom (MBS)
      (n=183) or not MBS (n=240) and MS without being MBS (n=57) with a 1.70 severity
      unit change in the MBS group for a decrease of 66.1% from baseline (p<0.0001
      versus baseline) over 52 weeks. A further improvement of dyspareunia, namely 0.33
      severity unit (19.4%), was observed with continuing treatment from 12 weeks to 52
      weeks. Similar results were observed on vaginal dryness and irritation/itching.
      Highly significant beneficial effects (p<0.0001 versus baseline for all) were
      observed at gynecological examination on vaginal secretions, color, epithelial
      integrity and epithelial surface thickness. CONCLUSION: The present study shows,
      in addition to the parallel benefits on the three symptoms of VVA, that the
      choice of any of the MS symptoms as being or not being MBS by women has no
      influence on the observed therapeutic effect (NCT01256671).

PMID- 25771043
TI  - Effect of the DGAT1 K232A genotype of dairy cows on the milk metabolome and
      proteome.
AB  - Diglyceride O-acyltransferase 1 (DGAT1) is the enzyme that catalyzes the
      synthesis of triglycerides from diglycerides and acyl-coenzyme A. The DGAT1 K232A
      polymorphism was previously shown to have a significant influence on bovine milk
      production characteristics (milk yield, protein content, fat content, and fatty
      acid composition). The mechanism of this influence has, however, not been
      elucidated. In this study, metabolomics ((1)H-nuclear magnetic resonance) and
      proteomics (laser chromatography-tandem mass spectrometry) were applied to
      determine the serum and lipid metabolite composition and milk fat globule
      membrane proteome of milk samples from cows with the DGAT1 KK and AA genotypes.
      The milk samples from cows with the DGAT1 KK genotype contained more stomatin,
      sphingomyelin, choline, and carnitine, and less citrate, creatine or
      phosphocreatine, glycerol-phosphocholine, mannose-like sugar, acetyl sugar
      phosphate, uridine diphosphate (UDP)-related sugar, and orotic acid compared with
      milk samples from cows with the DGAT1 AA genotype. Based on these results, we
      propose that the differences between the DGAT1 genotypes may be related to
      stomatin-sphingomyelin lipid rafts as well as structural (cell membrane)
      differences in epithelial cells of the mammary gland. In conclusion, our study
      shows that, in addition to previously described changes in triglyceride
      composition, cows differing in DGAT1 polymorphism differ in their milk proteome
      and metabolome, which may help in further understanding the effect of the DGAT1
      K232A polymorphism on milk production characteristics. 

PMID- 25771044
TI  - Self-assembled beta-lactoglobulin-oleic acid and beta-lactoglobulin-linoleic acid
      complexes with antitumor activities.
AB  - beta-Lactoglobulin (beta-LG) can bind to fatty acids such as oleic acid (OA) and
      linoleic acid (LA). Another whey protein, alpha-lactalbumin (alpha-LA), can also
      bind to OA to give the complex alpha-LA-OA, which has antitumor properties. Based
      on reports that the activity of alpha-LA-OA is highly dependent on OA, as well as
      the acquisition of similar complexes using other proteins, such as lysozyme and
      lactoferrin, we speculated whether beta-LG could also kill tumor cells after
      binding to other fatty acids. Therefore, we prepared complexes of beta-LG with OA
      (beta-LG-OA) and LA (beta-LG-LA) in the current study and evaluated them in terms
      of antitumor activity and thermostability using the methylene blue method and
      differential scanning calorimetry, respectively. The structural features of these
      complexes were also evaluated using fluorescence spectroscopy and circular
      dichroism. The binding dynamics of OA and LA to beta-LG were studied using
      isothermal titration calorimetry. Cell viability results revealed that beta-LG-LA
      and beta-LG-OA exhibited similar antitumor activities. Interestingly, the binding
      of beta-LG to LA led to an increase in its thermostability, whereas its binding
      to OA had very little effect. The environments of the tryptophan residues in the
      beta-LG-OA and beta-LG-LA complexes were very different, with the residues being
      blue- and red-shifted, respectively. Furthermore, the hydrophobic regions in beta
      LG were buried after binding of OA, which was slightly changed in beta-LG-LA.
      Circular dichroism results showed that beta-LG-OA enhanced the tertiary
      structure, which was partially lost in beta-LG-LA. There were more binding sites
      for OA than for LA on beta-LG, although the binding constants of the 2 fatty
      acids were similar, with both acids interacting with the protein though van der
      Waals and hydrogen bonding interactions. This study could help provide a deeper
      understanding of the structural basis for formation of antitumor protein-fatty
      acid complexes. 

PMID- 25771045
TI  - Effects of spray-drying conditions on the chemical, physical, and sensory
      properties of cheese powder.
AB  - Dairy powders are produced to increase the shelf life of fresh dairy products and
      for use as flavoring agents. In this study, 24 cheese powders produced under 7
      different conditions were used to investigate the effects of spray-drying
      parameters (e.g., inlet air temperature, atomization pressure, and outlet air
      temperature) on the quality of white cheese powder. Composition, color, physical
      properties, reconstitution, and sensory characteristics of white cheese powders
      were determined. The results revealed that the white cheese powders produced in
      this study had low moisture content ratios and water activity values. High outlet
      air temperatures caused browning and enhanced Maillard reactions. Additionally,
      high outlet air temperatures increased wettability and dispersibility and
      decreased the solubility of white cheese powders. Free fat content was positively
      correlated with inlet air temperature and negatively correlated with outlet air
      temperature and atomization pressure. Sensory analyses revealed that white cheese
      powder samples had acceptable sensory characteristics with the exception of the
      sample produced at an outlet air temperature of 100 degrees C, which had high
      scores for scorched flavor and color and low scores for cheese flavor. 

PMID- 25771046
TI  - Effect of dietary phosphorus on intestinal phosphorus absorption in growing
      Holstein steers.
AB  - The effect of dietary P intake on intestinal P absorption was evaluated in
      growing Holstein steers. Diets varying in P content (0.15, 0.27, 0.36, and 0.45%,
      DM basis) were fed to 8 steers (174+/-10kg of BW) fitted with permanent duodenal
      and ileal cannulas in a replicated 4*4 Latin square with 14-d periods. Ytterbium
      labeled corn silage and cobalt-EDTA were used as particulate and liquid phase
      markers, respectively, to measure digesta flow. Duodenal and ileal samples and
      spot urine samples were collected every 9 h from d 11 to 14. Total fecal
      collection was conducted on d 11 to 14 with fecal bags. Blood samples were
      collected from the coccygeal vessel on d 14. Feed, digesta, and fecal samples
      were analyzed for total P and inorganic P. Data were analyzed using PROC GLIMMIX
      in SAS with a model including treatment, square, period, and interaction of
      treatment and square. Preplanned contrasts were used to evaluate linear and
      quadratic treatment effects. Results were reported as least squares means. Dry
      matter intake (mean=4.90kg/d, 2.8% of BW) and apparent DM digestibility
      (mean=78.1%) were unaffected by treatment. Duodenal and ileal flow of total P
      increased linearly with increasing P intake (13.4, 18.5, 23.0, and 27.4g/d; 6.80,
      7.87, 8.42, and 10.4g/d). Increasing P intake increased the quantity of P
      absorbed from the small intestine linearly (6.96, 11.1, 14.6, and 17.2g/d), but
      absorption efficiency was unchanged (mean=59.6%). Phosphorus was absorbed on a
      net basis from the large intestine, but this was not affected by treatment and
      was a small proportion of total P absorption. Blood inorganic P increased
      linearly with increased dietary P (4.36, 6.31, 7.68, and 8.5mg/dL) and salivary P
      secretion was unchanged (mean=5.79g/d), suggesting that rumen function was
      prioritized during short-term P deficiency. These data showing an absence of
      change in absorption efficiency and salivary P secretion in the face of short
      term P deficiency may be used to improve published models of P digestion,
      absorption, and metabolism. 

PMID- 25771047
TI  - Activation of signal transducer and activator of transcription 5 (STAT5) is
      linked to beta1-integrin protein abundance in unilaterally milked bovine mammary
      glands.
AB  - Prolactin (PRL) is important in the regulation of milk synthesis in mammary
      epithelial cells (MEC). In cattle, circulating levels of PRL are not limiting,
      suggesting the possible involvement of other factors that may control the
      response to PRL at the cellular level. The effects of milking frequency (MF) on
      milk synthesis are controlled locally within mammary glands and involve PRL
      signaling. To further investigate this relationship between MF and PRL signaling,
      udder halves of 17 dairy cows were milked either 4 times a day (4*) or once a day
      (1*) for 14 d in early lactation. Mammary biopsies were obtained 3 to 5h
      following milking from both udder halves of 10 cows, and changes in PRL and
      associated pathways were measured. The abundance of STAT5A mRNA was higher after
      4* milking, whereas that of the PRL receptor (PRLR) and STAT3 were lower relative
      to that after 1* milking. In 4* mammary tissues, the protein levels of STAT5,
      activated STAT5, and beta1-integrin were higher, whereas the those of the long
      isoform of PRL receptor and activated STAT3 were lower than 1* tissues. The
      activation of STAT5 correlated strongly with major milk protein mRNA abundance
      (r=0.86 to 0.94) and beta1-integrin protein levels (r=0.91). These results
      confirm that major milk protein gene expression is associated with STAT5
      activation and suggests that the STAT5 and beta1-integrin signaling pathways are
      linked. Modulation of beta1-integrin abundance in response to changes in MF may
      be a mechanism that controls the MEC ability to respond to PRL and therefore its
      secretory activity. 

PMID- 25771048
TI  - Performance of early-lactation dairy cows as affected by dietary starch and
      monensin supplementation.
AB  - The objective of this study was to evaluate the effect of postpartum dietary
      starch content and monensin supplementation throughout the periparturient period
      and into early lactation on production performance of dairy cows during early
      lactation. Prior to parturition, primiparous (n=21) and multiparous (n=49)
      Holstein cows were fed a common controlled-energy close-up diet with a daily
      topdress of either 0 or 400mg/d monensin. From d 1 to 21 postpartum, cows were
      fed a high-starch (HS; 26.2% starch, 34.3% NDF, 22.7% ADF, 15.5% CP) or low
      starch (LS; 21.5% starch, 36.9% NDF, 25.2% ADF, 15.4% CP) total mixed ration with
      a daily topdress of either 0mg/d of monensin or 450mg/d monensin (MON),
      continuing with prepartum topdress treatment assignment. From d 22 through 63
      postpartum, cows were fed HS and continued with their assigned daily topdress.
      Interactions of starch content and MON supplementation were not significant for
      any of the variables measured. Cows fed HS from wk 1 to 3 postpartum had higher
      early-lactation milk yields (starch * week interaction) compared with LS cows,
      but HS cows also had lower percentages of milk fat, true protein, lactose, and
      total solids during the same period, resulting in similar yields of energy
      corrected milk (ECM) between starch treatments. Cows fed HS had higher early
      lactation dry matter intake (DMI; starch * week interaction) and lost less body
      condition score during wk 1 to 3, contributing to improved energy balance
      postpartum. No effect of starch treatment was observed on apparent total-tract
      dry matter or starch digestibilities assessed during d 18 to 19 (+/-2)
      postpartum, although cows fed the LS diet had greater apparent total-tract NDF
      digestibility compared with cows fed the HS diet. Cows fed MON had higher DMI and
      higher milk yields during the first 9 wk of lactation. However, all cows had
      similar yields of ECM because of trends for lower milk fat content during early
      lactation. In part because of similar yields of ECM between these treatments and
      higher DMI for cows fed MON, ECM per DMI during the first 9 wk of lactation was
      not affected by MON treatment. There was no effect of MON treatment on apparent
      total-tract dry matter, NDF, or starch digestibilities. Overall, cows fed more
      propiogenic diets in early lactation (HS or MON) had increased milk yield and DMI
      during the immediate postpartum period, indicating that diets with greater
      propiogenic capacity do not have detrimental effects on early-lactation DMI. 

PMID- 25771049
TI  - Metabolism of early-lactation dairy cows as affected by dietary starch and
      monensin supplementation.
AB  - The objective of this study was to evaluate the effect of dietary starch content
      and monensin (MON) on metabolism of dairy cows during early lactation. Before
      parturition, primiparous (n=21) and multiparous (n=49) Holstein cows were fed a
      common controlled-energy close-up diet with a daily topdress of either 0 or
      400mg/d monensin. From d 1 to 21 postpartum, cows were fed a high-starch (HS;
      26.2% starch, 34.3% neutral detergent fiber, 22.7% acid detergent fiber, 15.5%
      crude protein) or low-starch (LS; 21.5% starch, 36.9% neutral detergent fiber,
      25.2% acid detergent fiber, 15.4% crude protein) total mixed ration with a daily
      topdress of either 0mg/d monensin (CON) or 450mg/d monensin (MON), continuing
      with prepartum topdress assignment. From d 22 through 63 postpartum, all cows
      were fed HS and continued with the assigned topdress treatment until d 63. Cows
      fed HS had higher plasma glucose and insulin and lower nonesterified fatty acids
      (NEFA) than cows fed LS during d 1 to 21 postpartum. Cows fed LS had elevated
      early-lactation beta-hydroxybutyrate (BHBA) compared with cows fed HS. Cows fed
      HS had greater insulin resistance and increased plasma haptoglobin in the early
      lactation period. There was no effect of MON on postpartum plasma NEFA. Cows fed
      MON had higher plasma glucose compared with CON cows, which was driven by a MON *
      parity interaction in which primiparous cows fed MON had greater plasma glucose
      concentrations than cows fed CON. Cows fed MON had lower plasma BHBA compared
      with CON, which was contributed to by a MON * parity interaction in which
      primiparous cows fed MON had lower BHBA concentrations than CON. Starch treatment
      had no effect on overall liver triglyceride content. Primiparous cows fed MON had
      increased liver triglyceride content compared with CON primiparous cows, and
      multiparous cows fed MON had decreased liver triglyceride content compared with
      CON cows. Multiparous cows fed LS with MON had higher liver glycogen content than
      multiparous cows fed the LS without MON, with no effect of MON treatment for
      multiparous cows fed HS. There was no effect of starch or MON treatment on liver
      capacity to oxidize propionate to CO2, and effects of starch on gluconeogenesis
      were not significant. Cows fed MON tended to have greater capacity to convert
      propionate to glucose than CON. Supplementation with MON increased the ratio of
      glucose to CO2, which indicated that cows fed MON had a greater propensity to
      convert propionate to glucose. Overall, cows fed more propiogenic diets in early
      lactation (high starch or monensin) exhibited improved energy metabolism during
      early lactation. 

PMID- 25771050
TI  - Comparison of methods to determine methane emissions from dairy cows in farm
      conditions.
AB  - Nutritional and animal-selection strategies to mitigate enteric methane (CH4)
      depend on accurate, cost-effective methods to determine emissions from a large
      number of animals. The objective of the present study was to compare 2 spot
      sampling methods to determine CH4 emissions from dairy cows, using gas
      quantification equipment installed in concentrate feeders or automatic milking
      stalls. In the first method (sniffer method), CH4 and carbon dioxide (CO2)
      concentrations were measured in close proximity to the muzzle of the animal, and
      average CH4 concentrations or CH4/CO2 ratio was calculated. In the second method
      (flux method), measurement of CH4 and CO2 concentration was combined with an
      active airflow inside the feed troughs for capture of emitted gas and
      measurements of CH4 and CO2 fluxes. A muzzle sensor was used allowing data to be
      filtered when the muzzle was not near the sampling inlet. In a laboratory study,
      a model cow head was built that emitted CO2 at a constant rate. It was found that
      CO2 concentrations using the sniffer method decreased up to 39% when the distance
      of the muzzle from the sampling inlet increased to 30cm, but no muzzle-position
      effects were observed for the flux method. The methods were compared in 2 on-farm
      studies conducted using 32 (experiment 1) or 59 (experiment 2) cows in a switch
      back design of 5 (experiment 1) or 4 (experiment 2) periods for replicated
      comparisons between methods. Between-cow coefficient of variation (CV) in CH4 was
      smaller for the flux than the sniffer method (experiment 1, CV=11.0 vs. 17.5%,
      and experiment 2, 17.6 vs. 28.0%). Repeatability of the measurements from both
      methods were high (0.72-0.88), but the relationship between the sniffer and flux
      methods was weak (R(2)=0.09 in both experiments). With the flux method CH4 was
      found to be correlated to dry matter intake or body weight, but this was not the
      case with the sniffer method. The CH4/CO2 ratio was more highly correlated
      between the flux and sniffer methods (R(2)=0.30), and CV was similar (6.4-8.8%).
      In experiment 2, cow muzzle position was highly repeatable (0.82) and influenced
      sniffer and flux method results when not filtered for muzzle position. It was
      concluded that the flux method provides more reliable estimates of CH4 emissions
      than the sniffer method. The sniffer method appears to be affected by variable
      air-mixing conditions created by geometry of feed trough, muzzle movement, and
      muzzle position. 

PMID- 25771051
TI  - Short communication: Improving accuracy of Jersey genomic evaluations in the
      United States and Denmark by sharing reference population bulls.
AB  - The effect on prediction accuracy for Jersey genomic evaluations of Danish and US
      bulls from using a larger reference population was assessed. Each country
      contributed genotypes from 1,157 Jersey bulls to the reference population of the
      other. Data were separated into reference (US only, Danish only, and combined US
      Danish) and validation (US only and Danish only) populations. Depending on trait
      (milk, fat, and protein yields and component percentages; productive life;
      somatic cell score; daughter pregnancy rate; 14 conformation traits; and net
      merit), the US reference population included 2,720 to 4,772 bulls and cows with
      traditional evaluations as of August 2009; the Danish reference population
      included 635 to 996 bulls. The US validation population included 442 to 712 bulls
      that gained a traditional evaluation between August 2009 and December 2013; the
      Danish validation population included 105 to 196 bulls with multitrait across
      country evaluations on the US scale by December 2013. Genomic predicted
      transmitting abilities (GPTA) were calculated on the US scale using a selection
      index that combined direct genomic predictions with either traditional predicted
      transmitting ability for the reference population or traditional parent averages
      (PA) for the validation population and a traditional evaluation based only on
      genotyped animals. Reliability for GPTA was estimated from the reference
      population and August 2009 traditional PA and PA reliability. For prediction of
      December 2013 deregressed daughter deviations on the US scale, mean August 2009
      GPTA reliability for Danish validation bulls was 0.10 higher when based on the
      combined US-Danish reference population than when the reference population
      included only Danish bulls; for US validation bulls, mean reliability increased
      by 0.02 when Danish bulls were added to the US reference population. Exchanging
      genotype data to increase the size of the reference population is an efficient
      approach to increasing the accuracy of genomic prediction when the reference
      population is small. 

PMID- 25771052
TI  - Including overseas performance information in genomic evaluations of Australian
      dairy cattle.
AB  - In dairy cattle, the rate of genetic gain from genomic selection depends on
      reliability of direct genomic values (DGV). One option to increase reliabilities
      could be to increase the size of the reference set used for prediction, by using
      genotyped bulls with daughter information in countries other than the evaluating
      country. The increase in reliabilities of DGV from using this information will
      depend on the extent of genotype by environment interaction between the
      evaluating country and countries contributing information, and whether this is
      correctly accounted for in the prediction method. As the genotype by environment
      interaction between Australia and Europe or North America is greater than between
      Europe and North America for most dairy traits, ways of including information
      from other countries in Australian genomic evaluations were examined. Thus,
      alternative approaches for including information from other countries and their
      effect on the reliability and bias of DGV of selection candidates were assessed.
      We also investigated the effect of including overseas (OS) information on
      reliabilities of DGV for selection candidates that had weaker relationships to
      the current Australian reference set. The DGV were predicted either using
      daughter trait deviations (DTD) for the bulls with daughters in Australia, or
      using this information as well as OS information by including deregressed proofs
      (DRP) from Interbull for bulls with only OS daughters in either single trait or
      bivariate models. In the bivariate models, DTD and DRP were considered as
      different traits. Analyses were performed for Holstein and Jersey bulls for milk
      yield traits, fertility, cell count, survival, and some type traits. For
      Holsteins, the data used included up to 3,580 bulls with DTD and up to 5,720
      bulls with only DRP. For Jersey, about 900 bulls with DTD and 1,820 bulls with
      DRP were used. Bulls born after 2003 and genotyped cows that were not dams of
      genotyped bulls were used for validation. The results showed that the combined
      use of DRP on bulls with OS daughters only and DTD for Australian bulls in either
      the single trait or bivariate model increased the coefficient of determination
      [(R(2)) (DGV,DTD)] in the validation set, averaged across 6 main traits, by 3% in
      Holstein and by 5% in Jersey validation bulls relative to the use of DTD only.
      Gains in reliability and unbiasedness of DGV were similar for the single trait
      and bivariate models for production traits, whereas the bivariate model performed
      slightly better for somatic cell count in Holstein. The increase in R(2)
      (DGV,DTD) as a result of using bulls with OS daughters was relatively higher for
      those bulls and cows in the validation sets that were less related to the current
      reference set. For example, in Holstein, the average increase in R(2) for milk
      yield traits when DTD and DRP were used in a single trait model was 23% in the
      least-related cow group, but only 3% in the most-related cow group. In general,
      for both breeds the use of DTD from domestic sources and DRP from Interbull in a
      single trait or bivariate model can increase reliability of DGV for selection
      candidates. 

PMID- 25771053
TI  - Effect of intrauterine infusion of an organic-certified product on uterine
      health, survival, and fertility of dairy cows with toxic puerperal metritis.
AB  - The objective was to evaluate the effect of intrauterine infusion of an organic
      certified product (Optimum UterFlush, Van Beek Natural Science, Orange City, IA)
      on uterine health, survival, and fertility of cows affected with toxic puerperal
      metritis (TPM) in an organic dairy farm. Cows with TPM were defined as having an
      abnormally enlarged uterus and a fetid watery red-brown vaginal discharge,
      associated with systemic illness and fever (rectal temperature >=39.5 degrees C),
      within 12 d postpartum. Cows diagnosed with TPM (n=220; study d 0) were blocked
      by parity (1 and >=2) and randomly assigned into 1 of 2 intrauterine treatments
      applied every other day for a total of 3 applications: (1) control (CON)=200mL of
      povidone iodine diluted in 2L of distilled water (n=113); (2) Optimum UterFlush
      (UF)=3.75mL diluted in 117mL of distilled water (n=107). All enrolled cows
      received hypertonic saline solution (500mL 7.2% i.v.), dextrose (500mL 50% i.v.),
      and oral aspirin (5 boluses/d). Outcome variables for treatment efficacy included
      fever and presence of fetid vaginal discharge at study d 6 and 14, survival at
      study d 6 and 14 and at 30 and 100 DIM, and reproductive performance. Control
      variables were parity, BCS at enrollment, calving season, and milk yield.
      Occurrence of fever at d 6 and 14 was not different between the 2 treatment
      groups. Presence of fetid vaginal discharge at d 6 and 14 was lower in cows
      treated with UF compared with cows in the CON group (10.7 vs. 28% and 1.1 vs.
      9.1%). The odds (95% confidence interval) for survival and remaining in the farm
      at study d 6 and 14 and at 30 and 100 DIM for cows in the UF treatment were 4.67
      (1.38-15.8), 2.77 (1.25-6.10), 3.13 (1.22-8.02), and 2.82 (1.38-5.71) times the
      odds of cows in the CON group, respectively. The odds of AI until 150 DIM and the
      interval from calving to first AI were not different between the 2 treatments.
      However, pregnancy was affected by treatment; the odds (95% confidence interval)
      of pregnancy at the first AI, 150 DIM, and 300 DIM for cows treated with UF were
      2.15 (1.05-4.40), 1.81 (1.04-3.15), and 1.92 (1.09-3.38) times the odds of cows
      in the CON group, respectively. Days to pregnancy were similar in both treatment
      groups, but the number of artificial inseminations per pregnancy were different
      (2.69 vs. 2.02 for cows in the CON and UF treatments). Results indicate that cows
      with TPM administered intrauterine infusion of Optimum UterFlush had higher odds
      of recovering and improved reproductive performance compared with cows treated
      with povidone iodine. 

PMID- 25771054
TI  - Short communication: Hepatic progesterone-metabolizing enzymes cytochrome P450 2C
      and 3A in lactating cows during thermoneutral and heat stress conditions.
AB  - Two experiments were performed to determine the effects of heat stress (HS) and
      insulin on hepatic mRNA abundance of enzymes responsible for metabolizing
      progesterone [cytochrome P450 2C and 3A (CYP2C and CYP3A)]. To distinguish the
      direct effects of HS from decreased dry matter intake, cohorts were pair fed (PF)
      in thermoneutral conditions to match the intake of the HS cows during both
      experiments. In the first experiment, multiparous late-lactation Holstein cows
      (n=12, 305+/-33 d in milk) housed in climate-controlled chambers were subjected
      to 2 experimental periods: (1) thermoneutral (TN) conditions (18 degrees C, 20%
      humidity) with ad libitum intake (TN and well fed) for 9 d; and (2) either HS
      conditions (cyclical temperature 31-40 degrees C, 20% humidity) fed for ad
      libitum intake (n=6), or TN conditions and PF to match the HS animal (n=6) for 9
      d. To evaluate hepatic gene expression during experiment 1, biopsies were
      obtained at the end of each period. In the second experiment, multiparous mid
      lactation Holstein cows (n=12, 136+/-8 DIM) were housed and fed in conditions
      similar to those described for the first experiment. Liver biopsies were obtained
      immediately before and after an insulin tolerance test administered on d 6 of
      each period. No effects of exogenous insulin were observed on any of the tested
      variables, nor were there interactions between environment (TN/HS or well fed/PF)
      and insulin administration. Heat stress decreased hepatic CYP2C expression during
      both experiments. The relative abundance of CYP3A was not affected by
      environmental conditions in the late-lactation cows (first experiment), but was
      reduced by HS in the mid-lactation cows (second experiment). Interestingly,
      during experiment 2, hepatic CYP3A expression also decreased during PF. These
      results suggest that HS reduces the capacity of the liver to metabolize
      progesterone through distinct effects on CYP2C and CYP3A, and that the effects
      appear to vary based upon stage of lactation. Ultimately, HS may affect
      reproductive outcomes by reducing the abundance of the enzymes responsible for
      the breakdown of progesterone. This reduction could serve as a beneficial
      adaptation for rescuing early embryos or may be detrimental, as it affects
      feedback mechanisms necessary for proper cyclicity. 

PMID- 25771055
TI  - Effect of reference population size and available ancestor genotypes on
      imputation of Mexican Holstein genotypes.
AB  - The effects of reference population size and the availability of information from
      genotyped ancestors on the accuracy of imputation of single nucleotide
      polymorphisms (SNP) were investigated for Mexican Holstein cattle. Three
      scenarios for reference population size were examined: (1) a local population of
      2,011 genotyped Mexican Holsteins, (2) animals in scenario 1 plus 866 Holsteins
      in the US genotype database (GDB) with genotyped Mexican daughters, and (3)
      animals in scenario 1 and all US GDB Holsteins (338,073). Genotypes from 4 chip
      densities (2 low density, 1 mid density, and 1 high density) were imputed using
      findhap (version 3) to the 45,195 markers on the mid-density chip. Imputation
      success was determined by comparing the numbers of SNP with 1 or 2 alleles
      missing and the numbers of differently predicted SNP (conflicts) among the 3
      scenarios. Imputation accuracy improved as chip density and numbers of genotyped
      ancestors increased, and the percentage of SNP with 1 missing allele was greater
      than that for 2 missing alleles for all scenarios. The largest numbers of
      conflicts were found between scenarios 1 and 3. The inclusion of information from
      direct ancestors (dam or sire) with US GDB genotypes in the imputation of Mexican
      Holstein genotypes increased imputation accuracy by 1 percentage point for low
      density genotypes and by 0.5 percentage points for high-density genotypes, which
      was about half the gain found with information from all US GDB Holsteins. A
      larger reference population and the availability of genotyped ancestors improved
      imputation; animals with genotyped parents in a large reference population had
      higher imputation accuracy than those with no or few genotyped relatives in a
      small reference population. For small local populations, including genotypes from
      other related populations can aid in improving imputation accuracy. 

PMID- 25771056
TI  - Short communication: Genetic variation of riboflavin content in bovine milk.
AB  - Riboflavin (vitamin B2) is an essential water-soluble vitamin; elderly people and
      adolescents in particular can have poor riboflavin status. In Western diets, milk
      and dairy products are primary sources of riboflavin, but little is known about
      the natural variation within and among bovine breeds, and how genetic and
      environmental factors can affect the riboflavin content in milk. As a part of the
      Danish-Swedish Milk Genomics Initiative, the aim of the study was to quantify
      milk riboflavin content using reverse-phase HPLC in 2 major Danish dairy breeds.
      The results showed substantial interbreed differences in milk riboflavin content.
      Milk from Danish Jersey cows contained significantly higher levels of riboflavin
      (1.93mg/L of milk) than milk from Danish Holstein cows (1.40mg/L of milk).
      Furthermore, genetic analyses revealed high heritabilities in both breeds (0.52
      for Danish Holstein and 0.31 for Danish Jersey). A genomic association study
      found 35 significant single nucleotide polymorphisms (false discovery rate<0.10)
      to be associated with riboflavin content in milk in Jersey cows (all on BTA14 and
      BTA17), and 511 significant single nucleotide polymorphisms in Holstein cows
      spread over 25 different autosomes with BTA13 and BTA14 having the most promising
      quantitative trait loci. The best candidate gene found within the identified
      quantitative trait loci was SLC52A3, a riboflavin transporter gene, which was
      among the significant markers on BTA13 in Holstein cows. 

PMID- 25771057
TI  - Room-temperature phosphorescence determination of melamine in dairy products
      using l-cysteine-capped Mn-doped zinc sulfide (ZnS) quantum dots.
AB  - A simple, sensitive, and precise room-temperature phosphorescence method was
      developed for the determination of melamine in dairy products using l-cysteine
      capped Mn-doped zinc sulfide (ZnS) quantum dots as a probe. This method is based
      on the quenching of the phosphorescence signal of quantum dots by the interaction
      with melamine. Under optimum conditions, phosphorescence intensity was quenched
      by various concentrations of melamine in a linear range from 50 to 500ng/mL, with
      a detection limit of 5.95ng/mL in 10 mM phosphate buffer (pH 7.4). The relative
      standard deviation for 5 replicate measurements was 0.15%. The developed method
      was applied to dairy products to determine melamine concentrations; recovery
      values ranged from 96.3 to 104.7%. 

PMID- 25771058
TI  - Evaluation of hyperketonemia risk period and screening protocols for early
      lactation dairy cows.
AB  - The objectives of this study were to describe the onset of hyperketonemia, the
      number of positive hyperketonemia test results, and the duration of the longest
      hyperketonemic period during the first 42 d in milk (DIM) in dairy cows.
      Furthermore, we set out to evaluate test characteristics of single and repeated
      measurements of beta-hydroxybutyric acid (BHBA) during this period to diagnose
      hyperketonemia. Using an electronic handheld meter, 252 cows from 3 farms were
      tested twice weekly for hyperketonemia (blood BHBA >=1.2 mmol/L) during the first
      42 DIM, resulting in 12 test results per cow (i.e., in lactation wk 0.5 to 6).
      Prevalence and incidence of hyperketonemia were calculated for the 12 examination
      days and the 42-d period, respectively. Test characteristics for the diagnosis of
      hyperketonemia were calculated for 4 different testing scenarios (testing all
      cows 1, 2, 3, or 6 times during the first 42 DIM) and 2 different gold-standard
      definitions (BHBA >=1.2 mmol/L at least once during the observation period or
      BHBA >=1.2 mmol/L at least twice during the observation period). Mean prevalence
      of hyperketonemia was 11.8%, ranging from 9.6% in lactation wk 0.5 and 2.0 to
      14.6% in lactation wk 5.5. In total, 134 cows (53.2%) had at least 1 positive
      hyperketonemia test result during the whole 42-d period. Of these cows, 46.3% had
      only 1 positive result. The median first positive hyperketonemia test result was
      in lactation wk 2.0 [interquartile range (IQR) 1.0-3.5]. Median frequency of
      positive test results in cows affected by hyperketonemia was 2 positive test
      results (IQR 1-3). Median duration of the longest hyperketonemic period per cow
      affected was 1 examination interval (3-4 d; IQR 1-2). Considering a minimum of 1
      positive hyperketonemia test result during the first 42 DIM as the gold standard,
      sensitivity of a single BHBA measurement during this period to diagnose
      hyperketonemia was 21%. A weekly testing protocol had a sensitivity of 72%.
      Specificity was 100% in both cases. Considering a minimum of 2 positive
      hyperketonemia test results as the gold standard, sensitivity and specificity of
      a single BHBA measurement during the first 42 DIM were 33 and 97%, respectively.
      A weekly testing protocol provided sensitivity and specificity of 91 and 83%,
      respectively. We conclude that the risk period for hyperketonemia lasts at least
      until lactation wk 6, which should be considered when planning hyperketonemia
      screening programs. Test characteristics of screening protocols depend on testing
      frequency. 

PMID- 25771059
TI  - Dry period plane of energy: Effects on feed intake, energy balance, milk
      production, and composition in transition dairy cows.
AB  - The objective was to investigate the effect of different dry cow feeding
      strategies on the degree of ketonemia postpartum. Epidemiologic studies provide
      evidence of an association between elevated beta-hydroxybutyrate (BHBA)
      concentrations in postpartum dairy cows and a decreased risk for reproductive
      success as well as increased risk for several diseases in early lactation, such
      as displacement of the abomasum and metritis. The plane of energy fed to cows in
      the prepartum period has been shown to influence ketogenesis and the degree of
      negative energy balance postpartum. Our hypothesis was that a high-fiber,
      controlled-energy diet (C) fed during the dry period would lead to a lower degree
      of hyperketonemia in the first weeks postpartum compared with either a high
      energy diet (H), or a diet where an intermediate level of energy would only be
      fed in the close-up period (starting at 28d before expected parturition),
      following the same controlled-energy diet in the far-off period. Hyperketonemia
      in this study was defined as a blood BHBA concentration of >=1.2mmol/L. Holstein
      cows (n=84) entering parity 2 or greater were enrolled using a randomized block
      design and housed in individual tiestalls. All treatment diets were fed for ad
      libitum intake and contained monensin. Cows received the same fresh cow ration
      after calving. Blood samples were obtained 3 times weekly before and after
      calving and analyzed for BHBA and nonesterified fatty acids (NEFA). Milk
      components, production, and dry matter intake were recorded and energy balance
      was calculated. Repeated measures ANOVA was conducted for the outcomes dry matter
      intake, energy balance, BHBA and NEFA concentrations, milk and energy-corrected
      milk yield, as well as milk composition. Predicted energy balance tended to be
      less negative postpartum in group C and cows in this group had fewer episodes of
      hyperketonemia compared with both the intermediate group and group H in the first
      3 wk after calving. Postpartum BHBA and NEFA concentrations over time were
      highest in group H and lowest in group C, whereas milk production was not
      affected by prepartum plane of energy. Analysis of milk fatty acid composition
      showed a higher yield of preformed fatty acids in group H compared with group C,
      suggesting higher lipid mobilization for cows fed H. In this study, a 1-group,
      controlled-energy dry period approach decreased the degree of negative energy
      balance as well as the number of episodes and degree of hyperketonemia
      postpartum. 

PMID- 25771060
TI  - Evaluation of between-cow variation in milk urea and rumen ammonia nitrogen
      concentrations and the association with nitrogen utilization and diet
      digestibility in lactating cows.
AB  - Concentrations of milk urea N (MUN) are influenced by dietary crude protein
      concentration and intake and could therefore be used as a biomarker of the
      efficiency of N utilization for milk production (milk N/N intake; MNE) in
      lactating cows. In the present investigation, data from milk-production trials
      (production data set; n=1,804 cow/period observations from 21 change-over
      studies) and metabolic studies involving measurements of nutrient flow at the
      omasum in lactating cows (flow data set; n=450 cow/period observations from 29
      studies) were used to evaluate the influence of between-cow variation on the
      relationship of MUN with MNE, urinary N (UN) output, and diet digestibility. All
      measurements were made on cows fed diets based on grass silage supplemented with
      a range of protein supplements. Data were analyzed by mixed-model regression
      analysis with diet within experiment and period within experiment as random
      effects, allowing the effect of diet and period to be excluded. Between-cow
      coefficient of variation in MUN concentration and MNE was 0.13 and 0.07 in the
      production data set and 0.11 and 0.08 in the flow data set, respectively. Based
      on residual variance, the best model for predicting MNE developed from the
      production data set was MNE (g/kg)=238 + 7.0 * milk yield (MY; kg/d) - 0.064 *
      MY(2) - 2.7 * MUN (mg/dL) - 0.10 body weight (kg). For the flow data set,
      including both MUN and rumen ammonia N concentration with MY in the model
      accounted for more variation in MNE than when either term was used with MY alone.
      The best model for predicting UN excretion developed from the production data set
      (n=443) was UN (g/d)=-29 + 4.3 * dry matter intake (kg/d) + 4.3 * MUN + 0.14 *
      body weight. Between-cow variation had a smaller influence on the association of
      MUN with MNE and UN output than published estimates of these relationships based
      on treatment means, in which differences in MUN generally arise from variation in
      dietary crude protein concentration. For the flow data set, between-cow variation
      in MUN and rumen ammonia N concentrations was positively associated with total
      tract organic matter digestibility. In conclusion, evaluation of phenotypic
      variation in MUN indicated that between-cow variation in MUN had a smaller effect
      on MNE compared with published responses of MUN to dietary crude protein
      concentration, suggesting that a closer control over diet composition relative to
      requirements has greater potential to improve MNE and lower UN on farm than
      genetic selection. 

PMID- 25771061
TI  - Technical note: Validation of a system for monitoring individual feeding behavior
      and individual feed intake in dairy cattle.
AB  - The objective of this study was to validate an electronic system for monitoring
      individual feeding behavior and feed intake (Intergado Ltd., Contagem, Minas
      Gerais, Brazil) in freestall-housed dairy cattle. No data have been published
      that validate either the behavioral measurement or the feed intake of this
      system. Feeding behavior data were recorded for 12 Holstein cows over 5d using an
      Intergado system and time-lapse video. The cows were fitted with an ear tag
      containing a unique passive transponder and provided free access to 12 feed bins.
      The system documented the visit duration and feed intake by recording the animal
      identification number, bin number, initial and final times, and the difference
      between feed weight at start and end of each feed bin visit. These data were
      exported to Intergado web software and reports were generated. Electronic data on
      animal behavior were compared with video data collected during the same
      evaluation period. An external scale was used to manually measure and validate
      the electronic system's ability to monitor dairy cow feed intake for each feed
      bin visit. The feed intake was manually measured for 4-h time periods and
      compared with the sum of the feed intake recorded by the monitoring system for
      each cow visit during the same time period. Video and manual weight data were
      regressed on the electronic feeding behavior and feeding intake data to evaluate
      the precision of the monitoring system. The Intergado system presented high
      values for specificity (99.9%) and sensitivity (99.6%) for cow detection. The
      visit duration and feed intake per visit collected using the electronic
      monitoring system were similar to the video and manual weighing data,
      respectively. The difference between the feed intake measured manually and the
      sum of the electronically recorded feed intake was less than 250g (25,635+/-2,428
      and 25,391+/-2,428g estimated using manual weighing and the electronic system,
      respectively). In conclusion, the Intergado system is a reasonable tool to
      monitor feeding behavior and feed intake for freestall-housed dairy cows. 

PMID- 25771062
TI  - Effect of nitrogen fertilization rate and regrowth interval of grass herbage on
      methane emission of zero-grazing lactating dairy cows.
AB  - Dairy cattle farming in temperate regions often relies on grass herbage (GH)
      based diets but the effect of several grass management options on enteric CH4
      emission has not been fully investigated yet. We investigated the combined effect
      of N fertilization rate and length of regrowth period of GH (predominantly
      ryegrass) on CH4 emission from lactating dairy cows. In a randomized block
      design, 28 lactating Holstein-Friesian dairy cows received a basal diet of GH and
      compound feed [85:15; dry matter (DM) basis]. Treatments consisted of GH cut
      after 3 or 5 weeks of regrowth, after receiving either a low (20kg of N/ha) or a
      high (90kg of N/ha) fertilization rate after initial cut. Feed intake,
      digestibility, milk production and composition, N and energy balance, and CH4
      emission were measured during a 5-d period in climate respiration chambers after
      an adaptation to the diet for 12d. Cows were restricted-fed during measurements
      and mean DM intake was 15.0+/-0.16kg/d. Herbage crude protein content varied
      between 76 and 161g/kg of DM, and sugar content between 186 and 303g/kg of DM.
      Fat- and protein-corrected milk (FPCM) and feed digestibility increased with
      increased N fertilization rates and a shorter regrowth interval. Increasing the N
      fertilization rate increased daily CH4 emission per cow (+10%) and per unit of DM
      intake (+9%), tended to increase the fraction of gross energy intake emitted as
      CH4 (+7%), and (partly because of the low crude protein content for the low
      fertilized GH) only numerically reduced CH4 per unit of FPCM. The longer regrowth
      interval increased CH4 emission per unit of FPCM (+14%) compared with the shorter
      regrowth interval, but did not affect CH4 emission expressed in any other unit.
      With increasing N fertilization CH4 emission decreased per unit of digestible
      neutral detergent fiber intake (-13%) but not per unit of digestible organic
      matter intake. There was no interaction of the effect of N fertilization rate and
      regrowth interval on CH4 emission, but effects of N fertilization were generally
      most distinct with GH of 5 wk regrowth. The present results suggest that altering
      grass quality through an increase of N fertilization and a shorter regrowth
      interval can reduce CH4 emission in zero-grazing dairy cows, depending on the
      unit in which it is expressed. The larger amount of CH4 produced per day and cow
      with the more intensively managed GH is compensated by a higher feed
      digestibility and FPCM yield. 

PMID- 25771063
TI  - Adipose and liver gene expression profiles in response to treatment with a
      nonsteroidal antiinflammatory drug after calving in grazing dairy cows.
AB  - The peripartal or transition period in dairy cattle is often characterized by an
      inflammatory state that, if not controlled, could be detrimental to production,
      health, and fertility. Approaches to control the postpartal degree of
      inflammation include treatments with nonsteroidal antiinflammatory drugs (NSAID)
      postcalving, which have improved cow production and health. To date, most of the
      research on NSAID has been conducted in confinement cows that reach milk
      production levels substantially greater than those on pasture. Furthermore,
      little data are available on the effect of NSAID on the mRNA expression of
      inflammation and metabolism-related genes. Transcription regulation is an
      important mechanism of inflammation and metabolic control. The present study was
      conducted to examine hepatic and adipose tissue gene expression in response to
      injections of an NSAID, carprofen, on 1, 3, and 5 d after calving. Grazing
      Holstein-Friesian cows from a control group and 1 treated with carprofen during
      the first 5 d postcalving were used. Liver and subcutaneous adipose tissue
      biopsies were harvested at -1, 1, and 2 wk relative to parturition. More than 30
      genes associated with fatty acid oxidation, growth hormone/insulin-like growth
      factor-1 axis, hepatokines, lipoprotein metabolism, gluconeogenesis, and
      inflammation were analyzed. After calving, data suggest that both tissues respond
      to inflammation signals at the onset of lactation. Administration of NSAID led to
      greater hepatic expression of pyruvate dehydrogenase kinase, isozyme 4 (PDK4),
      which helps regulate gluconeogenesis, and microsomal triglyceride transfer
      protein (MTTP), important for the assembly and secretion of very low-density
      lipoproteins. In adipose tissue, NSAID administration resulted in greater
      expression of the inflammation-related genes interleukin-1, beta (IL1B),
      interleukin-6 receptor (IL6R), toll-like receptor 4 (TLR4), and chemokine (C-C
      motif) ligand 5 (CCL5). The data support the role of inflammation as a normal
      component of the homeorhetic adaptations to lactation and reveal a possible
      mechanism of action of carprofen in transition dairy cows, but do not reflect an
      effect of this NSAID on the extent of the peripartum inflammation. 

PMID- 25771064
TI  - A non-randomized study in consecutive patients with postcholecystectomy
      refractory biliary leaks who were managed endoscopically with the use of multiple
      plastic stents or fully covered self-expandable metal stents (with videos).
AB  - BACKGROUND: Endoscopic management of postcholecystectomy biliary leaks is widely
      accepted as the treatment of choice. However, refractory biliary leaks after a
      combination of biliary sphincterotomy and the placement of a large-bore (10F)
      plastic stent can occur, and the optimal rescue endotherapy for this situation is
      unclear. OBJECTIVE: To compare the clinical effectiveness of the use of a fully
      covered self-expandable metal stent (FCSEMS) with the placement of multiple
      plastic stents (MPS) for the treatment of postcholecystectomy refractory biliary
      leaks. DESIGN: Prospective study. SETTING: Two tertiary-care referral academic
      centers and one general district hospital. PATIENTS: Forty consecutive patients
      with refractory biliary leaks who underwent endoscopic management. INTERVENTIONS:
      Temporary placement of MPS (n = 20) or FCSEMSs (n = 20). MAIN OUTCOME
      MEASUREMENTS: Clinical outcomes of endotherapy as well as the technical success,
      adverse events, need for reinterventions, and prognostic factors for clinical
      success. RESULTS: Endotherapy was possible in all patients. After endotherapy,
      closure of the leak was accomplished in 13 patients (65%) who received MPS and in
      20 patients (100%) who received FCSEMSs (P = .004). The Kaplan-Meier (log-rank)
      leak-free survival analysis showed a statistically significant difference between
      the 2 patient populations (chi(2) [1] = 8.30; P < .01) in favor of the FCSEMS
      group. Use of <3 plastic stents (P = .024), a plastic stent diameter <20F (P =
      .006), and a high-grade biliary leak (P = .015) were shown to be significant
      predictors of treatment failure with MPS. The 7 patients in whom placement of MPS
      failed were retreated with FCSEMSs, resulting in closure of the leaks in all
      cases. LIMITATIONS: Non-randomized design. CONCLUSION: In our series, the results
      of the temporary placement of FCSEMSs for postcholecystectomy refractory biliary
      leaks were superior to those from the use of MPS. A randomized study is needed to
      confirm our results before further recommendations.

PMID- 25771065
TI  - Evaluation of a risk index for advanced proximal neoplasia of the colon.
AB  - BACKGROUND: A clinical risk index that uses distal colorectal findings at
      flexible sigmoidoscopy (FS) in conjunction with easily determined risk factors
      for advanced proximal neoplasia (APN) may be useful for tailoring or prioritizing
      screening with colonoscopy. OBJECTIVE: To conduct an external evaluation of a
      previously published risk index in a large, well-characterized cohort. DESIGN:
      Cross-sectional. SETTING: Teaching hospital and colorectal cancer screening
      center. PATIENTS: A total of 5139 asymptomatic persons aged 50 to 74 (54.9%
      women) with a mean age (+/-SD) of 58.3 (+/-6.2) years. INTERVENTIONS: Between
      2003 and 2011, all participants underwent a complete screening colonoscopy and
      removal of all polyps. MAIN OUTCOME MEASUREMENTS: Participants were classified as
      low, intermediate, or high risk for APN, based on their composite risk index
      scores. The concordance or c-statistic was used to measure discriminating ability
      of the risk index. RESULTS: A total of 167 persons (3.2%) had APN. The prevalence
      of those with APN among low-, intermediate-, and high-risk categories was 2.1%,
      2.9%, and 6.5%, respectively. High-risk individuals were 3.2 times more likely to
      have APN compared with those in the low-risk category. The index did not
      discriminate well between those in the low- and intermediate-risk categories. The
      c-statistic for the overall index was 0.62 (95% confidence interval, 0.58-0.66).
      LIMITATIONS: Distal colorectal findings were derived from colonoscopies and not
      FS itself. CONCLUSION: The risk index discriminated between those at low risk and
      those at high risk, but it had limited ability to discriminate between low- and
      intermediate-risk categories for prevalent APN. Information on other risk factors
      may be needed to tailor, or prioritize, access to screening colonoscopy.

PMID- 25771066
TI  - Anomalous accessory hepatic duct draining into the cystic duct in an asymptomatic
      patient: MRCP and ERCP findings.

PMID- 25771067
TI  - Factors that affect visibility during endoscopic hemostasis for upper GI
      bleeding: a prospective study.
AB  - BACKGROUND: Adequate visibility is an important factor for achieving successful
      endoscopic hemostasis for the treatment of upper GI bleeding (UGIB). The
      independent factors that affect visibility during endoscopic procedures have yet
      to be determined. OBJECTIVE: To determine the factors that affect endoscopic
      visibility and to create a model that can predict in which patients unacceptable
      visibility is suspected before emergent endoscopic procedures for UGIB. DESIGN:
      Prospective, observational study. SETTING: University-affiliated tertiary care
      hospital in South Korea. PATIENTS: A total of 121 patients admitted because of
      UGIB. INTERVENTION: Analysis of the visibility score of the emergency endoscopies
      for UGIB. MAIN OUTCOME MEASUREMENTS: Factors affecting the visibility score of
      endoscopy and a classification and regression tree (CART) model for predicting of
      visibility. RESULTS: The EGD time and the appearance of the nasogastric (NG) tube
      aspirate were independent factors that were significantly associated with
      visibility (EGD time, P<.001; red blood appearance in NG tube aspirate, P<.001;
      coffee grounds appearance of NG tube aspirate, P=.006). Based on these results, a
      CART model was developed by using 70 patients who had been allocated to the
      training set. The CART generated algorithms that proposed the use of the
      appearance of the NG tube aspirate and the EGD time (8.5 hours) to predict
      visibility. The sensitivity and specificity for predicting poor visibility were
      71.4% and 86.4%, respectively. CONCLUSION: The use of the CART model enables the
      prediction of which patients will have poor visibility during emergent endoscopy.

PMID- 25771068
TI  - Efficacy and safety of a partially covered duodenal stent for malignant
      gastroduodenal obstruction: a pilot study.
AB  - BACKGROUND: Duodenal stent placement has emerged as an effective and safe
      palliative treatment for patients with malignant gastroduodenal obstruction. An
      uncovered enteral stent, however, is susceptible to repeat stenosis because of
      tumor ingrowth. Although covering an enteral stent with a membrane prevents tumor
      ingrowth, stent migration continues to be a major unresolved problem. Partially
      covered metal stents may avoid both tumor ingrowth and stent migration.
      OBJECTIVE: To evaluate the clinical and technical efficacy and the safety of a
      partially covered duodenal stent for malignant gastroduodenal obstruction.
      DESIGN: Retrospective, observational study. SETTING: Tertiary-care medical
      center. PATIENTS: Twenty patients with malignant gastroduodenal obstruction
      received palliative treatment with partially covered duodenal stents.
      INTERVENTIONS: Endoscopic stent placement. MAIN OUTCOME MEASUREMENTS: Technical
      success, clinical success, patency, and adverse events. RESULTS: Stent placement
      was successful in all 20 patients (technical success rate, 100%), and symptoms
      improved in 19 (clinical success rate, 95%). The Gastric Outlet Obstruction
      Scoring System score improved significantly (P < .001). Eight patients (40%)
      developed tumor overgrowth, whereas none showed stent migration. Median stent
      patency was 79.5 days (range 13-198 days). Adverse events occurred in 3 patients,
      including 2 with transient bacteremia and 1 with asphyxia because of impaction of
      food material into the stent. LIMITATIONS: Single center, retrospective design,
      and a small number of patients. CONCLUSION: Partially covered duodenal stents
      were effective and safe for malignant gastroduodenal obstruction and may prevent
      tumor ingrowth and stent migration.

PMID- 25771070
TI  - Feeding difficulties in craniofacial microsomia: a systematic review.
AB  - Patients with craniofacial microsomia are at higher risk of developing
      obstructive sleep apnoea (OSA), as described in the previous article entitled
      "Obstructive sleep apnoea in craniofacial microsomia: a systematic review". These
      patients are also more likely to develop feeding difficulties. The present
      systematic review provides an overview of the literature on the prevalence,
      treatment, and follow-up of feeding difficulties in children with craniofacial
      microsomia (CFM). A search was performed in PubMed, Embase, Cochrane Library, and
      Web of Science for articles on CFM and feeding difficulties. The following data
      were extracted from the articles: number of patients, patient characteristics,
      presence of feeding difficulties, and the treatment and outcomes of feeding
      difficulties. Eight articles on CFM and feeding difficulties were included, two
      of which reported the prevalence of feeding difficulties (range 42-83%).
      Treatment mostly consisted of tube feeding. No information regarding follow-up
      was found in these articles. According to the literature, feeding difficulties
      are related to CFM. However, as there have been no prospective studies and few
      studies have presented objective measurements, no definitive conclusions can be
      drawn. Prospective studies are needed to determine the prevalence of feeding
      difficulties in patients with CFM.

PMID- 25771069
TI  - Efficacy of folic acid therapy in primary prevention of stroke among adults with
      hypertension in China: the CSPPT randomized clinical trial.
AB  - IMPORTANCE: Uncertainty remains about the efficacy of folic acid therapy for the
      primary prevention of stroke because of limited and inconsistent data. OBJECTIVE:
      To test the primary hypothesis that therapy with enalapril and folic acid is more
      effective in reducing first stroke than enalapril alone among Chinese adults with
      hypertension. DESIGN, SETTING, AND PARTICIPANTS: The China Stroke Primary
      Prevention Trial, a randomized, double-blind clinical trial conducted from May
      19, 2008, to August 24, 2013, in 32 communities in Jiangsu and Anhui provinces in
      China. A total of 20,702 adults with hypertension without history of stroke or
      myocardial infarction (MI) participated in the study. INTERVENTIONS: Eligible
      participants, stratified by MTHFR C677T genotypes (CC, CT, and TT), were randomly
      assigned to receive double-blind daily treatment with a single-pill combination
      containing enalapril, 10 mg, and folic acid, 0.8 mg (n = 10,348) or a tablet
      containing enalapril, 10 mg, alone (n = 10,354). MAIN OUTCOMES AND MEASURES: The
      primary outcome was first stroke. Secondary outcomes included first ischemic
      stroke; first hemorrhagic stroke; MI; a composite of cardiovascular events
      consisting of cardiovascular death, MI, and stroke; and all-cause death. RESULTS:
      During a median treatment duration of 4.5 years, compared with the enalapril
      alone group, the enalapril-folic acid group had a significant risk reduction in
      first stroke (2.7% of participants in the enalapril-folic acid group vs 3.4% in
      the enalapril alone group; hazard ratio [HR], 0.79; 95% CI, 0.68-0.93), first
      ischemic stroke (2.2% with enalapril-folic acid vs 2.8% with enalapril alone; HR,
      0.76; 95% CI, 0.64-0.91), and composite cardiovascular events consisting of
      cardiovascular death, MI, and stroke (3.1% with enalapril-folic acid vs 3.9% with
      enalapril alone; HR, 0.80; 95% CI, 0.69-0.92). The risks of hemorrhagic stroke
      (HR, 0.93; 95% CI, 0.65-1.34), MI (HR, 1.04; 95% CI, 0.60-1.82), and all-cause
      deaths (HR, 0.94; 95% CI, 0.81-1.10) did not differ significantly between the 2
      treatment groups. There were no significant differences between the 2 treatment
      groups in the frequencies of adverse events. CONCLUSIONS AND RELEVANCE: Among
      adults with hypertension in China without a history of stroke or MI, the combined
      use of enalapril and folic acid, compared with enalapril alone, significantly
      reduced the risk of first stroke. These findings are consistent with benefits
      from folate use among adults with hypertension and low baseline folate levels.
      TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00794885.

PMID- 25771072
TI  - Contributions from associative and explicit sequence knowledge to the execution
      of discrete keying sequences.
AB  - Research has provided many indications that highly practiced 6-key sequences are
      carried out in a chunking mode in which key-specific stimuli past the first are
      largely ignored. When in such sequences a deviating stimulus occasionally occurs
      at an unpredictable location, participants fall back to responding to individual
      stimuli (Verwey & Abrahamse, 2012). The observation that in such a situation
      execution still benefits from prior practice has been attributed to the
      possibility to operate in an associative mode. To better understand the
      contribution to the execution of keying sequences of motor chunks, associative
      sequence knowledge and also of explicit sequence knowledge, the present study
      tested three alternative accounts for the earlier finding of an execution rate
      increase at the end of 6-key sequences performed in the associative mode. The
      results provide evidence that the earlier observed execution rate increase can be
      attributed to the use of explicit sequence knowledge. In the present experiment
      this benefit was limited to sequences that are executed at the moderately fast
      rates of the associative mode, and occurred at both the earlier and final
      elements of the sequences. 

PMID- 25771071
TI  - Glyceollin, a novel regulator of mTOR/p70S6 in estrogen receptor positive breast
      cancer.
AB  - An estimated 70% of breast cancer tumors utilize estrogen receptor (ER) signaling
      to maintain tumorigenesis and targeting of the estrogen receptor is a common
      method of treatment for these tumor types. However, ER-positive (+) breast
      cancers often acquire drug resistant or altered ER activity in response to anti
      estrogens. Here we demonstrate glyceollin, an activated soy compound, has anti
      estrogen effects in breast cancers. We demonstrate through estrogen response
      element luciferase and phosphorylation-ER mutants that the effects of glyceollin
      arise from mechanisms distinct from conventional endocrine therapies. We show
      that glyceollin suppresses estrogen response element activity; however, it does
      not affect ER-alpha (alpha) phosphorylation levels. Additionally we show that
      glyceollin suppresses the phosphorylation of proteins known to crosstalk with ER
      signaling, specifically we demonstrate an inhibition of ribosomal protein S6
      kinase, 70 kDa (p70S6) phosphorylation following glyceollin treatment. Our data
      suggests a mechanism for glyceollin inhibition of ERalpha through the induced
      suppression of p70S6 and demonstrates novel mechanisms for ER inhibition.

PMID- 25771073
TI  - A rare case of paragonimiasis miyazakii with lung involvement diagnosed 7 years
      after infection: A case report and literature review.
AB  - We report a rare case of pulmonary paragonimiasis caused by Paragonimus miyazakii
      that showed pulmonary manifestations and a long-term clinical course after
      infection. A 45-year-old Japanese male developed cough and dyspnea in 2004 and
      was diagnosed with eosinophilic pneumonia. He had been treated with low-dose oral
      corticosteroid for 7 years. He recalled that he had consumed a large amount of
      raw freshwater crab (Geothelphusa dehaani) several weeks before he had been
      admitted for the first time, and that had been the only occasion when he had
      eaten this meat. The patient was referred to our hospital due to persistent
      hemoptysis, and his chest computed tomography scan showed pulmonary nodules and
      cavities, and his serum total IgE level was elevated. Bronchoscopy was performed,
      and ova were detected in the bronchoalveolar lavage fluid. The morphological
      examination of the ova and immunoserological examination yielded typical findings
      of P. miyazakii. Treatment with praziquantel improved his chest radiographic
      findings and a decrease of serum total IgE, as well as the values of
      immunoserological examination for P. miyazakii. The clinical course of this
      patient indicated that he had been infected with P. miyazakii for 7 years at
      least, which is unusual for paragonimiasis miyazakii.

PMID- 25771074
TI  - [Secondary prevention of ischemic non cardioembolic stroke].
AB  - Stroke patients are at high risk for recurrence or new occurrence of other
      cardiovascular events or cardiovascular mortality. It is estimated that a high
      percentage of non-cardioembolic ischemic stroke can be prevented by a suitable
      modification of lifestyle (diet and exercise), reducing blood pressure (BP) with
      antihypertensive medication, platelet aggregation inhibitors, statins and high
      intake reducing consumption of. Unfortunately the degree of control of the
      different risk factors in secondary prevention of stroke is low. The clinical
      practice guidelines show clear recommendations with corresponding levels of
      evidence, but only if implemented in a general way they will get a better primary
      and secondary stroke prevention. 

PMID- 25771075
TI  - Telomere shortening in mucosa surrounding the tumor: biosensor of field
      cancerization and prognostic marker of mucosal failure in head and neck squamous
      cell carcinoma.
AB  - OBJECTIVES: The aim of the present study was to investigate the pattern of
      telomere length and telomerase expression in cancer tissues and the surrounding
      mucosa (SM), as markers of field cancerization and clinical outcome in patients
      successfully treated for with head and neck squamous cell carcinoma (HNSCC).
      MATERIALS AND METHODS: This investigation was a prospective cohort study.
      Telomere length and levels of telomerase reverse transcriptase (TERT) transcripts
      were quantified by real-time PCR in cancer tissues and SM from 139 and 90
      patients with HNSCC, respectively. RESULTS: No correlation was found between age
      and telomere length in SM. Patients with short telomeres in SM had a higher risk
      of mucosal failure (adjusted HR=4.29). Patients with high TERT levels in cancer
      tissues had a higher risk of regional failure (HR=2.88), distant failure
      (HR=7.27), worse disease-specific survival (HR for related death=2.62) but not
      mucosal failure. High-risk patients having both short telomeres in SM and high
      levels of TERT in cancer showed a significantly lower overall survival (HR=2.46).
      CONCLUSIONS: Overall these findings suggest that telomere shortening in SM is a
      marker of field cancerization and may precede reactivation of TERT. Short
      telomeres in SM are strongly prognostic of mucosal failure, whereas TERT levels
      in cancer tissues increase with the aggressiveness of the disease and are
      prognostic of tumor spread.

PMID- 25771076
TI  - High metastatic node number, not extracapsular spread or N-classification is a
      node-related prognosticator in transorally-resected, neck-dissected p16-positive
      oropharynx cancer.
AB  - BACKGROUND: Due to unique biology and prognosis, precise identification of
      predictive parameters is critical for p16+ oropharyngeal squamous cell carcinoma
      (OPSCC). Prior studies showing absence of prognostication from extracapsular
      spread (ECS) and/or high N-classification in surgically-treated p16+ OPSCC
      necessitate new, evidence-based prognosticators. METHODS: A prospectively
      assembled cohort of 220, transoral surgery+neck dissection+/-adjuvant therapy
      treated, p16+ OPSCC patients was analyzed. Disease recurrence and disease
      specific survival (DSS) were primary endpoints. RESULTS: Median follow-up was 59
      (12-189) months. Distribution of metastatic node numbers was: 0 in 9.5% (n=21), 1
      in 33.6% (n=74), 2 in 17% (n=38), 3 in 14.5% (n=32), 4 in 8.2% (n=18), and ?5 in
      17% (n=37). ECS was recorded in 80% (n=159), and N2c-N3 in 17% (n=38). Adjuvant
      radiotherapy and chemoradiotherapy was administered in 44% and 34%. Recurrence
      developed in 22 patients (10%); 4 local, 5 regional, 2 regional and distant, and
      11 distant. The 3- and 5-year DSS estimates were 94.6% and 93%. Multivariable
      logistic regression identified ?5 nodes and T3-T4 classification as predictors
      for recurrence. In multivariable Cox analyses, ?5 nodes, T3-T4 classification and
      margins were prognostic for DSS. ECS, N2c-N3 classification and smoking were not
      prognostic. CONCLUSIONS: Metastatic node number, not ECS or high N-classification
      is an independent nodal predictor of outcomes in surgically-treated p16+ OPSCC
      patients. Despite high DSS (~80%), closer surveillance for recurrence is
      recommended for patients with ?5 metastatic nodes.

PMID- 25771077
TI  - Survival benefit for adjuvant radiation therapy in minor salivary gland cancers.
AB  - OBJECTIVES: The goal of the current study is to investigate the role of adjuvant
      radiation therapy (adjuvant RT) in minor salivary gland tumors (mSGT) using an
      established national database. METHODS: The Surveillance, Epidemiology, and End
      Results (SEER) database was used to identify patients treated with or without
      adjuvant RT for mSGT from 1988 to 2008. Regression analyses were performed to
      identify factors associated with improved overall survival (OS). RESULTS: Most
      tumors were located within the oral cavity (75%) followed by nasal
      cavity/paranasal sinuses (15%). Multivariate Cox analysis showed that adjuvant RT
      was associated with better OS compared to surgery alone. Using logistic
      regression analysis, we provide a novel web based tool for predicting survival
      impact of adjuvant RT in patients with mSGT. CONCLUSIONS: Adjuvant RT is
      associated with improved survival in patients with mSGT and adverse
      clinicopathologic factors such as advanced T/N category, adenoid cystic
      histology, high grade, and nasopharynx location.

PMID- 25771078
TI  - How environmental conditions impact mosquito ecology and Japanese encephalitis:
      an eco-epidemiological approach.
AB  - Japanese encephalitis (JE) is one of the major vector-borne diseases in Southeast
      Asia and the Western Pacific region, posing a threat to human health. In rural
      and suburban areas, traditional rice farming and intensive pig breeding provide
      an ideal environment for both mosquito development and the transmission of JEV
      among human beings. Combining surveillance data for mosquito vectors, human JE
      cases, and environmental conditions in Changsha, China, 2004-2009, generalized
      threshold models were constructed to project the mosquito and JE dynamics.
      Temperature and rainfall were found to be closely associated with mosquito
      density at 1, and 4month lag, respectively. The two thresholds, maximum
      temperature of 22-23 degrees C for mosquito development and minimum temperature
      of 25-26 degrees C for JEV transmission, play key roles in the ecology of JEV.
      The model predicts that, in the upper regime, a 1g/m(3) increase in absolute
      humidity would on average increase human cases by 68-84%. A shift in mosquito
      species composition in 2007 was observed, and possibly caused by a drought.
      Effective predictive models could be used in risk management to provide early
      warnings for potential JE transmission. 

PMID- 25771079
TI  - China's coastal wetlands: conservation history, implementation efforts, existing
      issues and strategies for future improvement.
AB  - China has approximately 5.80*10(6)ha coastal wetlands by 2014, accounting for
      10.82% of the total area of natural wetlands. Healthy coastal wetland ecosystems
      play an important role in guaranteeing the territory ecological security and the
      sustainable development of coastal zone in China. In this paper, the natural
      geography and the past and present status of China's coastal wetlands were
      introduced and the five stages (1950s-1970s, 1980s-1991, 1992-2002, 2003-2010 and
      2011-present) of China's coastal wetlands conservation from the foundation of the
      People's Republic in 1949 to present were distinguished and reviewed. Over the
      past decades, China has made great efforts in coastal wetland conservation, as
      signified by the implementation of coastal wetland restoration projects, the
      construction of coastal wetland nature reserves, the practice of routine
      ecological monitoring and two national wetland surveys, the promulgation of local
      wetland conservation statutes and specific regulations, the coordination
      mechanism to enhance management capacity, the wide development of coastal wetland
      research and public participation, and the extensive communication to strengthen
      international cooperation. Nonetheless, six major issues recently emerged in
      China's coastal wetland conservation are evidently existed, including the
      increasing threats of pollution and human activities, the increasing adverse
      effects of threaten factors on ecosystem function, the increasing threats of
      coastal erosion and sea-level rising, the insufficient funding for coastal
      wetlands conservation, the imperfect legal and management system for coastal
      wetlands, and the insufficient education, research and international cooperation.
      Although the threats and pressures on coastal wetlands conservation are still
      apparent, the future of China's coastal wetlands looks promising since the
      Chinese government understands that the sustainable development in coastal zone
      requires new attitudes, sound policies and concerted efforts at all levels. The
      major strategies for future improvement of China's coastal wetland conservation
      include: exploring effective measures in response to major threaten factors;
      improving the conservation and compensation system for coastal wetlands;
      strengthening coastal wetland legislation and management; increasing funds for
      coastal wetland conservation and research; and strengthening coastal wetland
      education and international cooperation. 

PMID- 25771080
TI  - A comparison of clinical-pathological characteristics between symptomatic and
      interval breast cancer.
AB  - BACKGROUND: An association between interval breast cancers (cancer detected after
      a normal mammogram and before the next scheduled mammogram) and tumour
      aggressiveness has been postulated which may reflect their relatively poor
      overall prognosis. The aim of this study was to evaluate known prognostic
      features of screen detected breast cancers compared to interval breast cancers.
      METHODS: Patients diagnosed with breast cancer between January 2010 and 2013 at a
      single unit of the National Breast Screening Program (NBSP) in Ireland and those
      between the ages of 50 and 65 diagnosed at a symptomatic breast clinic were
      included in the study. Patients who had not had a screening mammogram within the
      proceeding two years or had a previous history of breast cancer were excluded.
      Data were retrospectively collected on patient demographics, tumour type, grade,
      hormone receptor status and stage of disease at presentation. RESULTS: There were
      915 patients included in the study, with 92% (n = 844) diagnosed through the
      NBSP. Ductal carcinoma in-situ accounted for 19% (n = 160) of screen-detected
      breast cancers but only 2.8% of interval cancers (p < 0.05). The most common type
      of invasive cancer was invasive ductal carcinoma. Tumour grade was significantly
      higher in interval breast cancers (p < 0.05). Interval cancers were identified at
      a significantly higher stage (Stage 1 versus 2; p < 0.001) than screen-detected
      cancers. Interval breast cancers were less likely to be ER positive (76% versus
      81%; p < 0.05) and significantly more likely to over-express HER2 (20% vs 10%, p
      < 0.05) than screen-detected cancers. CONCLUSION: This study highlights the fact
      that interval cancers appear to have a number of adverse prognostic markers for
      overall breast cancer survival when compared to women with screen-detected breast
      cancers. Interval cancers were more likely to be invasive, of a higher grade and
      stage and with a greater predominance of HER2 and triple negative molecular
      subtypes. Therefore this heterogeneous group of tumours may be biologically more
      aggressive and account disproportionately to overall breast cancer mortality.

PMID- 25771081
TI  - Occult cancer in specimens of reduction mammaplasty aimed at symmetrization. A
      multicentric study of 2718 patients.
AB  - Women who have undergone surgical treatment for breast cancer often benefit from
      a contralateral reduction mammaplasty (CRM) aimed at symmetrization of the
      contralateral breast unaffected by the initial cancer. In our 7-year multicentric
      study (12 centers) of 2718 patients, incidence of CRM cancers (CRMc) was 1.47% (n
      = 40) [95% CI 1.05%-2.00%]. The CRMc group had significantly more initial mammary
      cancers of invasive lobular carcinoma (ILC, 22.5% vs 12.0%) and ductal carcinoma
      in situ (DCIS, 35.0% vs 21.6%) types than the healthy CRM group (p = 0.017).
      35.0% (n = 14) of patients had en bloc resection; 25.0% (n = 10) of surgical
      specimens were correctly oriented. En bloc resection and orientation of surgical
      specimens enable precise pinpointing of the CRMc. A salvage lumpectomy may be
      proposed as an option when margins are invaded. The histological distribution of
      the 40 CRMc (mean size 12.7 mm) was carcinoma in situ (CIS) 70%, ILC 12.5%,
      invasive ductal carcinoma (IDC) 12.5% and tubular carcinoma (TC) 5.0%. 

PMID- 25771082
TI  - Development and regression of the thyroglossal duct in mice.
AB  - The thyroid anlage develops in the foramen caecum area of the tongue, and
      migrates through the anterior neck towards its final position in front of the
      laryngeal cartilages. During migration, the thyroglossal duct, a temporary
      structure connecting the thyroid anlage and the foramen caecum, is recognized. In
      the present study, chronological changes and apoptosis in the thyroglossal duct
      of mice were investigated histochemically using an antibody against Nkx2-1,
      initially identified as a thyroid transcription factor 1 (TTF1), and the TUNEL
      reaction in consecutive serial sagittal sections. At embryonic day 10.00
      (E10.00), the thyroid anlage was Nkx2-1-immunoreactive and located just below the
      foramen caecum. As the thyroid anlage descended, the thyroglossal duct was formed
      at E10.25, being less than 10MUm in diameter. By E10.75, the Nkx2-1-positive
      thyroglossal duct had progressively elongated up to 100MUm. At E11.00 the
      thyroglossal duct began to disappear, beginning in its mid-portion, and finally
      became invisible at E11.50. At E11.00-12.00, apoptotic cells were found in an
      area where the thyroglossal duct was partially discontinuous. After E12.00,
      cartilaginous tissue of the hyoid bone anlage developed in the mid-portion of the
      area where the thyroglossal duct had regressed. Immunoreactivity for
      thyroglobulin, a marker of differentiated thyroid endocrine cells, was detected
      at E13.00. These results strongly suggest that the mouse thyroglossal duct
      disappears as a result of apoptosis before differentiation of the endocrine
      thyroid.

PMID- 25771083
TI  - How Ecology and Landscape Dynamics Shape Phylogenetic Trees.
AB  - Whether biotic or abiotic factors are the dominant drivers of clade
      diversification is a long-standing question in evolutionary biology. The
      ubiquitous patterns of phylogenetic imbalance and branching slowdown have been
      taken as supporting the role of ecological niche filling and spatial
      heterogeneity in ecological features, and thus of biotic processes, in
      diversification. However, a proper theoretical assessment of the relative roles
      of biotic and abiotic factors in macroevolution requires models that integrate
      both types of factors, and such models have been lacking. In this study, we use
      an individual-based model to investigate the temporal patterns of diversification
      driven by ecological speciation in a stochastically fluctuating geographic
      landscape. The model generates phylogenies whose shape evolves as the clade ages.
      Stabilization of tree shape often occurs after ecological saturation, revealing
      species turnover caused by competition and demographic stochasticity. In the
      initial phase of diversification (allopatric radiation into an empty landscape),
      trees tend to be unbalanced and branching slows down. As diversification proceeds
      further due to landscape dynamics, balance and branching tempo may increase and
      become positive. Three main conclusions follow. First, the phylogenies of
      ecologically saturated clades do not always exhibit branching slowdown. Branching
      slowdown requires that competition be wide or heterogeneous across the landscape,
      or that the characteristics of landscape dynamics vary geographically.
      Conversely, branching acceleration is predicted under narrow competition or
      frequent local catastrophes. Second, ecological heterogeneity does not
      necessarily cause phylogenies to be unbalanced--short time in geographical
      isolation or frequent local catastrophes may lead to balanced trees despite
      spatial heterogeneity. Conversely, unbalanced trees can emerge without spatial
      heterogeneity, notably if competition is wide. Third, short isolation time causes
      a radically different and quite robust pattern of phylogenies that are balanced
      and yet exhibit branching slowdown. In conclusion, biotic factors have a strong
      and diverse influence on the shape of phylogenies of ecologically saturating
      clades and create the evolutionary template in which branching slowdown and tree
      imbalance may occur. However, the contingency of landscape dynamics and resource
      distribution can cause wide variation in branching tempo and tree balance.
      Finally, considerable variation in tree shape among simulation replicates calls
      for caution when interpreting variation in the shape of real phylogenies.

PMID- 25771084
TI  - Relative distribution of gastrin-, CCK-8-, NPY- and CGRP-immunoreactive cells in
      the digestive tract of dorado (Salminus brasiliensis).
AB  - The endocrine cells (ECs) of the gastrointestinal mucosa form the largest
      endocrine system in the body, not only in terms of cell numbers but also in terms
      of the different produced substances. Data describing the association between the
      relative distributions of the peptide-specific ECs in relation to feeding habits
      can be useful tools that enable the creation of a general expected pattern of EC
      distribution. We aimed to investigate the distribution of ECs immunoreactive for
      the peptides gastrin (GAS), cholecystokinin (CCK-8), neuropeptide Y (NPY), and
      calcitonin gene-related peptide (CGRP) in different segments of the digestive
      tract of carnivorous fish dorado (Salminus brasiliensis) by using
      immunohistochemistry procedures. The distribution of endocrine cells
      immunoreactive for gastrin (GAS), cholecystokinin (CCK-8), neuropeptide Y (NPY),
      and calcitonin gene-related peptide (CGRP) in digestive tract of dorado S.
      brasiliensis was examined by immunohistochemistry. The results describe the
      association between the distribution of the peptide-specific endocrine cells and
      feeding habits in different carnivorous fish. The largest number of endocrine
      cells immunoreactive for GAS, CCK-8, and CGRP were found in the pyloric stomach
      region and the pyloric caeca. However, NPY-immunoreactive endocrine cells were
      markedly restricted to the midgut. The distribution pattern of endocrine cells
      identified in S. brasiliensis is similar to that found in other carnivorous
      fishes. 

PMID- 25771085
TI  - [Introduction. Venous thromboembolism in cancer patients].

PMID- 25771086
TI  - [Management of venous thromboembolism in oncological patients: Spanish clinical
      practice guidelines. Consensus SEACV-SEOM].

PMID- 25771087
TI  - [Long-term treatment with a low-molecular-weight heparin administered
      subcutaneously compared with a vitamin K antagonist: subanalysis of patients with
      cancer].
AB  - We performed a subanalysis of cancer patients enrolled in a clinical trial that
      compared long-term (6 months) treatment with a low-molecular-weight heparin
      (LMWH) administered subcutaneously or with acenocoumarol. The subanalysis
      assessed whether the characteristics of the tumor had an influence on the
      clinical response. A randomized open trial included 69 patients with cancer and
      symptomatic proximal deep vein thrombosis of the lower limbs. The tumor
      characteristics and treatment type were recorded. The main assessment criterion
      was the 12-month incidence of recurrent symptomatic venous thromboembolism (VTE).
      Sixty-one patients (88.4%) were analyzed. At the time of inclusion, the cancer
      characteristics and treatment were comparable between the 2 groups. Over the
      course of 12 months, the recurrent VTE was significantly greater in the elderly
      patients (71.5 +/- 6.4 vs. 62.0 +/- 15.1; p=.006). The logistic regression
      analysis showed no association between VTE recurrence and the location or extent
      of the tumor. However, the use of thrombogenic chemotherapy (p=.045) was
      independently associated with VTE recurrence, and longterm treatment with
      tinzaparin was almost a protective factor (p=.15). In this small sample, we
      observed an association between thrombogenic chemotherapy and recurrent VTE. The
      tendency towards a reduction in VTE recurrence at 12 months in patients with
      cancer in the LMWH group could be attributed to the effect of the full LMWH
      dosage.

PMID- 25771088
TI  - [Biomolecular markers in cancer-associated thromboembolism].
AB  - Patients with cancer have an increased risk of developing thromboembolism, which
      is associated with increased morbidity and mortality and hinders its clinical
      management. Cancer generates a hypercoagulable state that increases the
      generation of thrombin. This coagulation activation, along with the inflammatory
      changes fostered by the neoplastic cells, favors tumor progression at the local
      and distal level. In this review, we present the most salient aspects of the
      pathophysiology of hypercoagulability in cancer and list the hemostatic
      biomarkers that reflect this biological situation of hypercoagulability. These
      parameters can be used as risk factors to predict the probability of developing
      thrombosis, which help identify patients who can benefit from antithrombotic
      prophylaxis. 

PMID- 25771089
TI  - [The genetics of thrombosis in cancer].
AB  - Venous thromboembolism (VTE) is a multifactorial and complex disease in which the
      interaction of genetic factors (estimated at 60%) and environmental factors
      (e.g., the use of oral contraceptives, pregnancy, immobility and cancer)
      determine the risk of thrombosis for each individual. In particular, the
      association between thrombosis and cancer is well established. Approximately 20%
      of patients with cancer develop a thromboembolic event over the course of the
      natural history of the tumor process, with thrombosis being the second leading
      cause of death for these patients. One of the greatest challenges currently
      facing the field of oncology is the identification of patients at high risk of
      VTE who can benefit from thromboprophylaxis. Currently, there is a VTE risk
      prediction model for patients with cancer (the Khorana risk score); however, its
      ability to identify patients at high risk is very low. It is important to note
      that this score, which is based on five clinical parameters, ignores the genetic
      variability associated with VTE risk. In this article, we present the preliminary
      results of the Oncothromb study, whose objective is to develop an individual VTE
      risk prediction model for patients with cancer who are treated with outpatient
      chemotherapy. Our model includes the clinical and genetic data on each patient
      (Thrombo inCode((r)) genetic profile). Only by integrating multiple layers of
      biological information (clinical, plasmatic and genetic) we could obtain models
      that provide accurate information as to which patients are at high risk of
      developing a thromboembolic event associated with cancer so as to take
      appropriate prophylactic measures. 

PMID- 25771090
TI  - [Pulmonary embolism in patients with cancer: foundations of the EPIPHANY study].
AB  - Pulmonary thromboembolism (PE) is a common cause of morbidity and mortality in
      patients with cancer. Having cancer is an independent risk factor for death in
      the general series of patients with PE and is included as a variable in the
      prognostic scales of acute symptomatic PE. This fact limits the discriminatory
      power of these general scales for patients with cancer and has prompted the
      development of specific prognostic tools: POMPE-C and a scale derived from the
      RIETE registry. Whether the increased risk of death by PE in patients with cancer
      is due to complications related to the neoplasm or to a greater severity of the
      thromboembolic episode in this population has not been well studied. Moreover,
      the introduction of computed multidetector tomography in recent years has led to
      a growing diagnosis of incidental PE, which currently represents up to half of
      pulmonary embolisms in patients with cancer. The EPIPHANY study attempts to
      further the understanding of the characteristics of pulmonary embolisms in
      patients with cancer by including incidental and symptomatic events. Its primary
      objectives are a) to understand the clinical and epidemiological patterns of
      pulmonary embolism associated with cancer and b) to develop and validate a
      specific prognosis model for PE in this population. The registry includes
      variables of interest to oncology (cancer type and extent, oncospecific
      treatments, patient's functional condition, cancer progression), radiological
      variables (thrombotic burden, signs of ventricular overload and other findings),
      location of treatment (hospital or outpatient), acute complications and causes of
      death in patients with PE associated with cancer. 

PMID- 25771091
TI  - [Venous thrombosis of atypical location in patients with cancer].
AB  - Venous thromboembolism (VTE) is a complication that frequently occurs in patients
      with neoplastic diseases. Several models have therefore been developed to
      identify patient subgroups diagnosed with cancer who are at increased risk of
      developing VTE. The most common forms of thromboembolic episodes are deep vein
      thrombosis in the lower limbs and pulmonary thromboembolism. However, venous
      thrombosis is also diagnosed in atypical locations. There are few revisions of
      unusual cases of venous thrombosis. In most cases, VTE occurs in the upper limbs
      and in the presence of central venous catheters, pacemakers and defibrillators.
      We present the case of a patient diagnosed with breast cancer and treated with
      surgery, chemotherapy and radiation therapy who developed a thrombosis in the
      upper limbs (brachial and axillary). 

PMID- 25771092
TI  - [Venous thrombosis associated with central venous catheter use in patients with
      cancer].
AB  - The use of central venous catheters for various applications (administration of
      chemotherapy, blood products and others) in patients with cancer is increasingly
      frequent. The association between thrombosis and catheter use has been fully
      established but aspects such as its causes, diagnosis, prophylaxis and treatment
      have not. We describe a case of thrombosis in a patient with cancer treated with
      chemotherapy who carried a central venous catheter. We also perform a review of
      the risk factors, the role of the prophylaxis and the treatment. 

PMID- 25771093
TI  - Bilateral multiple pulmonary (18)F-FDG microembolisms demonstrated on PET/CT.

PMID- 25771094
TI  - Synchronous triple thymoma and true thymic hyperplasia simultaneously detected by
      (18)F FDG PET-CT.

PMID- 25771095
TI  - Redox-driven events in the human immunodeficiency virus type 1 (HIV-1) infection
      and their clinical implications.
AB  - Oxidative stress is a condition characterized by the imbalance between the
      production of reactive species (RS) or free radicals and their neutralization by
      the antioxidant defenses, leading to the accumulation of RS and their derived
      metabolites, with changes in the redox status of the cell. These RS can act on
      biological components and induce the oxidative and nitrosative reactions on
      lipids, proteins, and DNA. In this context, a wide variety of chronic diseases
      present oxidative stress as a part of the pathogenesis, including the human
      immunodeficiency virus type 1 (HIV-1) infection. The relationship between
      oxidative stress and HIV-1 infection lies in the fact that the RS species are
      important components of the innate immune response, and their derived metabolites
      and reactions participate in several events of the adaptative immune response. On
      the other hand, studies have shown specific roles for oxidative-driven events in
      both the host immunity and the virus biology. Undoubtedly, the occurrence of
      oxidative stress in HIV-1-infected patients has been implicated in disease
      progression, as well as in developing other secondary disorders, such as
      cardiovascular diseases, insulin resistance, and metabolic syndrome. This review
      aims to characterize the redox-driven events in the HIV-1 infection and their
      clinical implications in the disease features. 

PMID- 25771096
TI  - The epigenetic/noncoding origin of tumor dormancy.
AB  - Cancer stem cells (CSCs) have been implicated as the seeds of treatment
      resistance and metastasis, which are the most deadly features of a neoplasm.
      However, an unequivocal definition of the CSC phenotype is still missing. A
      common feature of normal and aberrant stem cells is their ability to enter a
      prolonged dormant state. Cancer dormancy is a key mechanism for treatment
      resistance and metastasis. Here we propose a unified definition of dormancy
      competent CSCs (DCCs) as the neoplastic subpopulation that can plastically
      alternate periods of dormancy and rapid growth. Irreversible DNA mutations can
      hardly account for this versatile behavior, and based on emerging evidence we
      propose that cancer dormancy is a nongenetic disease driven by the flexible
      nature of the epigenetic/noncoding interactome. 

PMID- 25771097
TI  - miRNAs in atherosclerotic plaque initiation, progression, and rupture.
AB  - Atherosclerosis is a chronic immune-inflammatory disorder that integrates
      multiple cell types and a diverse set of inflammatory mediators. miRNAs are
      emerging as important post-transcriptional regulators of gene expression in most,
      if not all, vertebrate cells, and constitute central players in many
      physiological and pathological processes. Rapidly accumulating experimental
      studies reveal their key role in cellular and molecular processes related to the
      development of atherosclerosis. We review current evidence for the involvement of
      miRNAs in early atherosclerotic lesion formation and in plaque rupture and
      erosion. We conclude with a perspective on the clinical relevance, therapeutic
      opportunities, and future challenges of miRNA biology in understanding the
      pathogenesis of this complex disease. 

PMID- 25771099
TI  - FamLinkX - implementation of a general model for likelihood computations for X
      chromosomal marker data.
AB  - The use of genetic markers located on the X chromosome has seen a significant
      increase in the last years and their utility has been well studied. This paper
      describes the software FamLinkX, freely available at http://www.famlink.se,
      implementing a new algorithm for likelihood computations accounting for linkage,
      linkage disequilibrium and mutations. It is obvious that such software is sought
      for among forensic users as more and more X-chromosomal markers become available.
      We provide some simulated examples demonstrating the utility of the
      implementation as well as its application in forensic casework. Though algebraic
      derivations are generally unfeasible, the paper outlines some theoretical
      considerations and provides a discussion on the validation of the software. The
      focus of this paper is to compare the software to existing methods in a forensic
      setting, perform a validation study as well as to provide an idea of the
      discriminatory power for X-chromosomal markers. 

PMID- 25771100
TI  - Sensitivity of preparation with rhTSH or thyroid hormone withdrawal using 131I
      whole body scans to identify metastases of differentiated thyroid cancer.
AB  - It has been reported that there is a higher sensitivity for Thyroid Hormone
      Withdrawal (THW) in detection of metastases of Differentiated Thyroid Cancer
      (DTC) when compared to Recombinant Human Thyroid-Stimulating Hormone (rhTSH).
      This study aims to confirm this reported difference in the sensitivity using
      radioiodine whole body scans (WBS). MATERIALS AND METHODS: In a retrospective
      study forty three patients with evidence or suspicion of metastatic
      differentiated thyroid cancer DTC (evaluated by thyroglobulin or abnormal
      findings in previous WBS) underwent WBS using of 24 h after oral administration
      of 370 MBq (131)I. The WBS was interpreted by two independent experienced
      observers categorizing their findings into a positive or negative for metastatic
      disease. The findings were controlled by stimulated thyroglobulin (TG)
      measurement and a two years follow-up. RESULTS: Of the evaluated patients, 14
      patients were prepared with rhTSH and 29 with THW. No statistical differences in
      patient characteristics were documented between the two groups (age, sex,
      thyroglobulin level, TSH level, type of cancer). In this study, no differences in
      the sensitivity of WBS of patients prepared with rhTSH or THW were found. There
      were 11 of 14 patients (78%) that were positive after rhTSH and 19 of 29 patients
      (65%) after THW. Metastatic disease was confirmed by stimulated thyroglobulin
      value and follow-up. CONCLUSION: In contrast to previously published data, this
      study couldn't found any differences in the sensitivity of rhTSH or THW for the
      preparation of DTC patients undergoing (131)I imaging.

PMID- 25771098
TI  - Autoimmune host-microbiota interactions at barrier sites and beyond.
AB  - The microbiota is considered to be an important factor influencing the
      pathogenesis of autoimmunity at both barrier sites and internal organs. Impinging
      on innate and adaptive immunity, commensals exert protective or detrimental
      effects on various autoimmune animal models. Human microbiome studies of
      autoimmunity remain largely descriptive, but suggest a role for dysbiosis in
      autoimmune disease. Humanized gnotobiotic approaches have advanced our
      understanding of immune-commensal interactions, but little is known about the
      mechanisms in autoimmunity. We propose that, similarly to infectious agents, the
      microbiota mediates autoimmunity via bystander activation, epitope spread, and,
      particularly under homeostatic conditions, via crossreactivity. This review
      presents an overview of the current literature concluding with outstanding
      questions in this field. 

PMID- 25771101
TI  - Epidural analgesia for cytoreductive surgery with peritonectomy and heated
      intraperitoneal chemotherapy.
AB  - PURPOSE: To evaluate epidural analgesia role after cytoreductive surgery with
      peritonectomy combined with heated intraperitoneal chemotherapy. METHODS: 101
      patients were retrospectively studied (between 2008 and 2012) to evaluate
      epidural analgesia effectiveness, tolerability and safety in this surgical
      context through the assessment of pain, detection of adverse events (nausea,
      vomiting, itching), temporary motor block, respiratory failure and coagulation
      profile in the post-operative period. RESULTS: The median duration of epidural
      analgesia was 5 [range 1-10] days. As regards pain relief, the median verbal
      numerical scale scores at rest and on movement were below 2 and 5 until the fifth
      post-operative day, respectively. 13% of patients suffered nausea, 4% vomit, and
      1% itching. No bradycardia or respiratory failure event was reported. 9.9% of
      patients had hypotension episodes. Coagulation reached normality only 3-4 days
      after surgery. 5 risky accidental dislodgments of epidural catheter occurred
      (prothrombine time INR > 1.5) without neurological complications. CONCLUSIONS:
      Epidural analgesia ensures adequate pain relief and is well tolerated by patients
      after cytoreductive surgery with peritonectomy combined with heated
      intraperitoneal chemotherapy. Hypotension is common in this context and careful
      monitoring of coagulation parameters, especially in the first 3 days after
      surgery, is advisable to reduce the risk of neuraxial complications.

PMID- 25771102
TI  - Utility of postoperative CEA for surveillance of recurrence after resection of
      primary colorectal cancer.
AB  - INTRODUCTION: To evaluate the usefulness of postoperative CEA levels in the
      surveillance of colorectal cancer patients. METHODS: Over a 56 month period a
      total of 569 patients with measured CEA levels underwent curative resection for
      colorectal cancer. The median follow up was 40 months, during which period
      recurrence occurred in 149. Serum CEA levels were measured at 6 monthly intervals
      starting from 3 months post resection. ROC was used to calculate the optimum cut
      off of CEA (5 ng/ml). RESULTS: Postoperative elevation of CEA levels were more
      frequent in patients with an aggressive primary colorectal cancer (grade, T stage
      and nodal disease; p < 0.05). In patients found to have colorectal recurrence, a
      significantly higher proportion of patients were resectable in the group with a
      non-elevated CEA (diagnosed by CT with PET imaging p < 0.05). The median interval
      between CEA elevation and diagnosis of recurrence (diagnostic interval) was 4
      weeks. CEA elevation led to a change in the routine surveillance program by
      bringing imaging forward by 2 months. CEA levels were a significant predictor of
      survival following resection of colorectal primary (CEA <=5-38 months, CEA >5-27
      months; p < 0.05). CEA (p < 0.05) retained its significance on multivariate
      analysis along with the T stage (p < 0.05). CONCLUSION: CEA is a predictor of
      recurrence, resectability and survival following resection of colorectal cancer.
      Furthermore, an elevated CEA has a short diagnostic interval (4 weeks) for
      detecting recurrent disease and therefore should mandate adjustment of the
      routine surveillance program with the next planned imaging being brought forward
      (2 months).

PMID- 25771103
TI  - An evaluation of the relationship between Enterobius vermicularis infestation and
      acute appendicitis in a paediatric population--A retrospective cohort study.
AB  - BACKGROUND: Enterobius vermicularis is an often unexpected finding in
      appendectomy specimen, most commonly seen in paediatric cases. Predicting the
      presence of E. vermicularis in the setting of appendectomy is important to avoid
      unnecessary appendectomy and associated morbidity. We sought to identify the
      incidence of E. vermicularis in a paediatric population undergoing appendectomy
      for clinically suspected acute appendicitis and identify predictive factors for
      E. vermicularis. METHODS: This study was performed in an 800-bed University
      Teaching Hospital, in the Republic of Ireland. We identified all paediatric
      appendectomies performed at our institute from January to December 2012 using
      prospectively maintained operating theatre logbooks. In-hospital Histopathology
      database, medical notes and operative findings were reviewed for each patient and
      relevant data recorded. Statistical analysis was performed using IBM SPSS,
      version 21. RESULTS: In total 182 paediatric appendectomies were performed during
      the year 2012 for clinically suspected acute appendicitis. Demographics included:
      Mean age 11.14 years (3-16), gender 1M: 1F. 58.8% of procedures were completed
      laparoscopically, 39% open and 2.2% were converted. The negative appendectomy
      rate was 22.5%. The annual incidence of E. vermicularis in acute appendicitis
      specimen from a paediatric cohort at our institute was 7% (1 in 14). In specimen
      containing E. vermicularis, 69% had no evidence of appendicitis and of those that
      had, no gangrene or perforation was seen. The presence of E. vermicularis in
      paediatric patients with RIF pain may be predicted by Eosinophilia (p = 0.016),
      normal WCC (p = 0.034) and normal Neutrophil count (p = 0.014). CONCLUSIONS: E.
      vermicularis is responsible for 7% of acute appendicitis. It is responsible for a
      significantly higher negative appendectomy rate which if predicted may avoid
      unnecessary appendectomy and associated morbidity.

PMID- 25771104
TI  - Diagnosing appendicitis with serum bilirubin level: Is there any problem?

PMID- 25771105
TI  - Neonatal and pediatric healthcare worldwide: A report from UNICEF.
AB  - The 2013 UNICEF annual report on child mortality concluded that between 1990 and
      2013, the annual number of deaths among children under-5 years of age has fallen
      to 6.6 million (uncertainty range, 6.3 to 7.0 million), corresponding to a 48%
      reduction from the 12.6 million deaths in 1990 (uncertainty range, 12.4 to 12.9
      million). About half of under-5 deaths occur in only five countries: India,
      Nigeria, Democratic Republic of the Congo, Pakistan and China. By 2050, close to
      40% of all live births will take place in Sub-Saharan Africa and 37% of the
      world's children under age five will live in the region. Most deaths can be
      attributable to preventable diseases. Pneumonia, diarrhea and malaria together
      killed roughly 2.2 million children under age five in 2012, accounting for a
      third of all under-five deaths. Emerging evidence has shown that children are at
      greater risk of dying before age five if they are born in rural areas, poor
      households, or to a mother denied basic education. While under-5 mortality was
      consistently reduced over the past 20 years, few progresses in reducing neonatal
      mortality as well as maternal mortality have been done. UNICEF is a leading
      partner in the Global Alliance for Vaccines and Immunization (GAVI), a far
      reaching public-private partnership dedicated to increasing children's access to
      vaccines in poor countries. Early diagnosis and appropriate low-cost therapy of
      maternal and neonatal diseases are the challenges of the coming years. Therefore,
      there is the need to promote new experimental and clinical researches and to
      translate results in clinical practice. Laboratory medicine is strategic for
      promoting and validating innovative methods for managing the most important
      causes of maternal, neonatal and under-5 deaths, as well as to consistently
      reduce the gap between bench and bedside. This may be achieved by a close
      cooperation between laboratory medicine and industries for the development of new
      diagnostic tools, especially low-cost disposables easily usable by everyone,
      namely mothers, for an earlier and specific therapeutic treatments of such
      diseases like sepsis and infections.

PMID- 25771106
TI  - Monitoring laboratory data across manufacturers and laboratories--A prerequisite
      to make "Big Data" work.
AB  - BACKGROUND: "The Percentiler" project provides quasi real-time access to patient
      medians across laboratories and manufacturers. This data can serve as
      "clearinghouse" for electronic health record applications, e.g., use of
      laboratory data for global health-care research. METHODS: Participants send their
      daily outpatient medians to the Percentiler application. After 6 to 8weeks, the
      laboratory receives its login information, which gives access to the user
      interface. Data is assessed by peer group, i.e., 10 or more laboratories using
      the same test system. Participation is free of charge. RESULTS: Participation is
      global with, to date, >120 laboratories and >250 instruments. Up to now, several
      reports have been produced that address i) the general features of the project,
      ii) peer group observations; iii) synergisms between "The Percentiler" and
      dedicated external quality assessment surveys. Reasons for long-term instability
      and bias (calibration- or lot-effects) have been observed for the individual
      laboratory and manufacturers. CONCLUSIONS: "The Percentiler" project has the
      potential to build a continuous, global evidence base on in vitro diagnostic test
      comparability and stability. As such, it may be beneficial for all stakeholders
      and, in particular, the patient. The medical laboratory is empowered for
      contributing to the development, implementation, and management of global health
      care policies.

PMID- 25771107
TI  - Two-hour diagnostic algorithms for early assessment of patients with acute chest
      pain--Implications of lowering the cardiac troponin I cut-off to the 97.5th
      percentile.
AB  - AIMS: Assessment of patients with suspected non-ST elevation myocardial
      infarction (NSTEMI) is based on cardiac troponin (cTn) levels with the 99th
      percentile as cut-off. However, cardiovascular risk starts already at lower
      troponin concentrations. We therefore, aimed to investigate the utility of 2-hour
      algorithms using the high-sensitivity cardiac troponin I (hs-cTnI) 97.5th
      percentile as cut-off which corresponds to the standard URL for most biomarkers.
      METHODS: Hs-cTnI was measured at presentation and 2h in 1624 chest pain patients.
      Diagnostic algorithms were developed applying hs-cTnI levels dichotomized at the
      99th and 97.5th percentiles combined with hs-cTnI changes and/or ECG findings.
      RESULTS: The prevalence of NSTEMI was 13.9%. The adjusted odds ratios for 1-year
      mortality were 2.7 (95% CI 1.4-5.1) for the 99th percentile and 3.1 (95% CI 1.6
      5.9) for the 97.5th percentile. The best-performing 99th percentile-based
      algorithms provided a positive predictive value (PPV) of 86.3% and a negative
      predictive value (NPV) of 99.3%. Using 97.5th percentile-based algorithms to
      define NSTEMI resulted in few reclassifications and yielded similar diagnostic
      estimates (PPV 85.4%, NPV 99.4%). CONCLUSION: The hs-cTnI 97.5th percentile
      integrated into 2-hour algorithms provided high diagnostic estimates and could,
      due to better prognostic properties serve as an alternative to the 99th
      percentile.

PMID- 25771108
TI  - Synthesis, crystal structure and biological evaluation of substituted
      quinazolinone benzoates as novel antituberculosis agents targeting
      acetohydroxyacid synthase.
AB  - Acetohydroxyacid synthase (AHAS) catalyzes the first essential biosynthetic step
      of branched-chain amino acids and is a biologically safe target against
      Mycobacterium tuberculosis (MTB). In our previous research, we used virtual
      screening to identify some novel AHAS inhibitors as potent antituberculosis
      agents. In this study, we synthesized twenty-four additional quinazolinone
      benzoates and explored their antitubercular activity. Five of these compounds
      displayed significant MTB-AHAS inhibition and their IC50 values were determined
      to be in the range of 6.50 MUM-12.08 MUM. Importantly, these compounds also
      exhibited strong in vitro activity (MICs in the range of 2.5-10 mg/L) and
      intracellular activity against clinically isolated extensively drug-resistant
      strains of M. tuberculosis. Taken together, these results indicated that the
      quinazolinone benzoate compounds should be regarded as promising lead compounds
      for the development of potent antituberculosis drugs with a novel mode of action.

PMID- 25771109
TI  - Synthesis and antibacterial evaluation of a novel series of synthetic
      phenylthiazole compounds against methicillin-resistant Staphylococcus aureus
      (MRSA).
AB  - Methicillin-resistant Staphylococcus aureus infections are a significant global
      health challenge in part due to the emergence of strains exhibiting resistance to
      nearly all classes of antibiotics. This underscores the urgent need for the rapid
      development of novel antimicrobials to circumvent this burgeoning problem.
      Previously, whole-cell screening of a library of 2,5-disubstituted thiazole
      compounds revealed a lead compound exhibiting potent antimicrobial activity
      against MRSA. The present study, conducting a more rigorous analysis of the
      structure-activity relationship of this compound, reveals a nonpolar, hydrophobic
      functional group is favored at thiazole-C2 and an ethylidenehydrazine-1
      carboximidamide moiety is necessary at C5 for the compound to possess activity
      against MRSA. Furthermore, the MTS assay confirmed analogs 5, 22d, and 25
      exhibited an improved toxicity profile (not toxic up to 40 MUg/mL to mammalian
      cells) over the lead 1. Analysis with human liver microsomes revealed compound 5
      was more metabolically stable compared to the lead compound (greater than eight
      fold improvement in the half-life in human liver microsomes). Collectively the
      results presented demonstrate the novel thiazole derivatives synthesized warrant
      further exploration for potential use as future antimicrobial agents for the
      treatment of multidrug-resistant S. aureus infections.

PMID- 25771110
TI  - Discovery of target based novel pyrrolyl phenoxy derivatives as antimycobacterial
      agents: an in silico approach.
AB  - A new series of pyrrolyl phenoxy derivatives bearing alkoxy linker were
      synthesized and evaluated for anti-tubercular activity (anti-TB) against
      Mycobacterium tuberculosis. Molecular modeling, pharmacophore constructed using
      GALAHAD to produce an effective alignment of data set and evaluated by Pareto
      ranking. The pharmacophore features were filtered by Surflex-dock study using
      enoyl ACP reductase from M. tuberculosis, which is one of the key enzymes
      involved in type II fatty acid biosynthesis pathway of M. tuberculosis. Compound
      6a27 showed the H-bond with NAD(+), whereas compound 6a26 showed H-bonds with
      Tyr158, Thr196, Met199 and NAD(+) that fitted well into the binding pocket of
      target InhA. The alkoxy linker bridge and acceptor groups with benzene ring were
      advantageous for anti-TB activity, which merit further investigation.

PMID- 25771111
TI  - Kleptochloroplast Enlargement, Karyoklepty and the Distribution of the
      Cryptomonad Nucleus in Nusuttodinium (= Gymnodinium) aeruginosum (Dinophyceae).
AB  - The unarmoured freshwater dinoflagellate Nusuttodinium (= Gymnodinium)
      aeruginosum retains a cryptomonad-derived kleptochloroplast and nucleus, the
      former of which fills the bulk of its cell volume. The paucity of studies
      following morphological changes to the kleptochloroplast with time make it
      unclear how the kleptochloroplast enlarges and why the cell ultimately loses the
      cryptomonad nucleus. We observed, both at the light and electron microscope
      level, morphological changes to the kleptochloroplast incurred by the enlargement
      process under culture conditions. The distribution of the cryptomonad nucleus
      after host cell division was also investigated. The volume of the
      kleptochloroplast increased more than 20-fold, within 120h of ingestion of the
      cryptomonad. Host cell division was not preceded by cryptomonad karyokinesis so
      that only one of the daughter cells inherited a cryptomonad nucleus. The fate of
      all daughter cells originating from a single cell through five generations was
      closely monitored, and this observation revealed that the cell that inherited the
      cryptomonad nucleus consistently possessed the largest kleptochloroplast for that
      generation. Therefore, this study suggests that some important cryptomonad
      nucleus division mechanism is lost during ingestion process, and that the
      cryptomonad nucleus carries important information for the enlargement of the
      kleptochloroplast. 

PMID- 25771112
TI  - Efficient human immunodeficiency virus (HIV-1) infection of cells lacking PDZD8.
AB  - PDZD8 can bind the capsid proteins of different retroviruses, and transient
      knockdown of PDZD8 results in a decrease in the efficiency of an early, post
      entry event in the retrovirus life cycle. Here we used the CRISPR-CAS9 system to
      create cell lines in which PDZD8 expression is stably eliminated. The PDZD8
      knockout cell lines were infected by human immunodeficiency virus (HIV-1) and
      murine leukemia virus as efficiently as the parental PDZD8-expressing cells.
      These results indicate that PDZD8 is not absolutely necessary for HIV-1 infection
      and diminishes its attractiveness as a potential target for intervention. 

PMID- 25771113
TI  - Agreement of the Kato-Katz test established by the WHO with samples fixed with
      sodium acetate analyzed at 6 months to diagnose intestinal geohelminthes.
AB  - The aim of this study was to evaluate the performance of the Kato-Katz test (WHO
      version) with stool samples from a rural area, fixed with sodium acetate (SAF).
      The Kato-Katz test was used to compare unfixed samples (conventional test) with
      the same samples containing SAF fixative at time 0 and at 6 months. The study
      included stools from 154 subjects. A marginally statistically significant
      decrease in prevalence was estimated only for hookworm, when comparing unfixed
      samples versus the SAF fixed samples read at 6 months (p=0.06). A significant
      reduction in parasite load was found for hookworm (p<0.01) and Trichuris
      trichiura (p<0.01) between the unfixed and the fixed sample read at 6 months, but
      not for Ascaris lumbricoides (p=0.10). This research suggests that the SAF
      fixative solution is a good option for transporting samples for diagnosis,
      especially in rural areas in developing countries. 

PMID- 25771114
TI  - Laboratory evaluation of aqueous leaf extract of Tephrosia vogelii against larvae
      of Aedes albopictus (Diptera: Culicidae) and non-target aquatic organisms.
AB  - Mosquito control using insecticides has been the most successful intervention
      known to reduce malaria prevalence or incidence. However, vector control is
      facing a threat due to the emergence of resistance to synthetic insecticides.
      Insecticides of botanical origin may serve as suitable alternative biocontrol
      techniques in the future. In this research, the leaf aqueous leachate of
      Tephrosia vogelii was evaluated for its toxicity against larvae of the most
      invasive mosquito worldwide, Aedes albopictus (Diptera: Culicidae), and toward
      adults of the water flea, Daphnia magna (Cladocera: Crustacea) and Oreochromis
      niloticus, two non-target aquatic organisms that share the same ecological niche
      of A. albopictus. The leaf aqueous leachate of T. vogelii was evaluated against
      fourth-instar larvae, non-blood fed 3-5 days old laboratory strains of A.
      albopictus under laboratory condition. In addition, the objective of the present
      work was to study the environmental safety evaluation for aquatic ecosystem.
      Mortality was then recorded after 7d exposure. The leaf aqueous leachate of T.
      vogelii showed high mosquitocidal activity against larvae of A. albopictus, with
      a LC50=1.18MUg/mL. However, it had a remarkable acute toxicity also toward adults
      of the non-target arthropod D. magna, with a LC50=0.47MUg/L and O. niloticus with
      a LC50=5.31MUg/L. The present findings have important implications in the
      practical control of mosquito larvae in the aquatic ecosystem, as the medicinal
      plants studied are commonly available in large quantities. The extract could be
      used in stagnant water bodies for the control of mosquitoes acting as vector for
      many communicable diseases. 

PMID- 25771115
TI  - Schwannoma of the olfactory nerve. Report of two cases and review of the
      literature.

PMID- 25771116
TI  - Surgical treatment for cervical spondylotic myelopathy in elderly patients: a
      retrospective study.
AB  - OBJECTIVE: To analyze perioperetive clinical features and outcomes of surgical
      treatment for cervical spondylotic myelopathy (CSM) in elderly patients. METHODS:
      From 2006 to 2013, we retrospectively reviewed 136 patients with CSM who
      underwent surgery. The patients were divided into two groups: 70 years or older
      (elderly group, 58 patients) and younger than 70 years (younger group, 78
      patients). The course of disease, surgical outcome, morbidities, and
      postoperative complications were analyzed. RESULTS: In the elderly group, follow
      up lasted 9-76 months (mean 39.6 months), the course of disease was 23.7 months
      (range 4-72 months). Anterior cervical decompression and fusions and posterior
      laminectomy and fixation were performed in 24 and 34 patients, respectively. The
      operative time averaged 103 min (range 48-210 min). In the younger group, follow
      up lasted 10-71 months (mean 37.8 months), the course of disease was 12.6 months
      (range 2-58 months). Anterior cervical decompression and fusions and posterior
      laminectomy and fixation were performed in 75 and three patients, respectively.
      The prevalence of chronic diseases and postoperative complications were higher in
      the elderly group than the younger group. The recovery rates of JOA score were
      40.82 +/- 11.20% in the elderly group and 64.10 +/- 22.61% in the younger group.
      The therapeutic effects of surgery were significantly better for the young
      patients than for the elderly. CONCLUSION: Elderly patients with CSM present long
      period and serious symptoms, and the degeneration of multiple organs. Surgical
      decompression for CSM appears to be a beneficial and safe procedure for older
      patients if properly handled, although the recovery rate is poorer than that of
      younger patients.

PMID- 25771117
TI  - MR imaging and cognitive impairment in MS: a neuroimaging-based mechanistic view.

PMID- 25771118
TI  - Clinical perspective - cough: an unmet need.
AB  - Cough is among the most common complaints for which individuals worldwide seek
      medical attention. The vast majority of cases of acute cough (<3 weeks duration)
      are due to acute viral upper respiratory tract infection (URI) (common cold).
      Fortunately, acute cough is typically transient and self-limited. However, should
      severe and/or persistent acute cough require pharmacological treatment,
      satisfactory therapeutic options are scarce. Narcotic antitussives are limited by
      unacceptable side effects at therapeutic doses, and most over-the-counter (OTC)
      remedies are not supported by adequate clinical trials. The goal in chronic cough
      (>8 weeks duration) is to meticulously evaluate and treat all potential
      underlying etiologies. Despite thorough investigation, a significant minority of
      patients will suffer refractory, unexplained cough. For this challenging
      population, safe, effective, non-narcotic antitussive therapies are desperately
      needed. 

PMID- 25771119
TI  - New indole glucosides as biosynthetic intermediates of camptothecin from the
      fruits of Camptotheca acuminata.
AB  - Six new indole glucosides (1-6) and fifteen known alkaloids (7-21) were isolated
      from the fruit of Camptotheca acuminata. The planar structures of 1-6 were
      determined on the basis of spectroscopic data analysis and their absolute
      configurations were established by CD. The isolated indole glucosides showed a
      clear biosynthetic pathway of camptothecin (7), which started from tryptamine and
      secologanin and was proposed by synthetic chemists previously. Particularly,
      compound 1 supplemented the process of the transformation from pumiloside (20) or
      3-epi-pumiloside (21) to camptothecin (7). In addition, camptothecin 10-O-beta-D
      glucopyranoside (13) and norcamptothecin (17), synthesized in the early
      structural modification of 7, were first isolated from the natural resources. The
      new compounds 1-6 were screened for their in vitro cytotoxicity but they did not
      show any exciting result. 

PMID- 25771120
TI  - Kaennacowanols A-C, three new xanthones and their cytotoxicity from the roots of
      Garcinia cowa.
AB  - Three new xanthones, named kaennacowanols A-C (1-3), along with nineteen known
      xanthones were isolated from the roots of Garcinia cowa Roxb. Their structures
      were determined by spectroscopic analysis. All isolated compounds were evaluated
      for their cytotoxicity against KB and HeLa cell lines. Compounds 17 and 22 showed
      good cytotoxicity against KB cell with IC50 values of 7.97 and 9.10MUM,
      respectively. On the other hand, compound 15 showed good cytotoxicity against
      HeLa cell with IC50 value of 9.34MUM.

PMID- 25771121
TI  - Isoxanthohumol--Biologically active hop flavonoid.
AB  - Isoxanthohumol (IXN), apart from xanthohumol (XN) and 8-prenylnaringenin (8PN),
      is one of the most important prenylflavonoids found in hops. Another natural
      source of this compound is a shrub Sophora flavescens, used in traditional
      Chinese medicine. Main dietary source of IXN is beer, and the compound is
      produced from XN during wort boiling. In the human body, the compound is O
      demethylated to 8PN, the strongest known phytoestrogen. This process takes place
      in the liver and in the intestine, where it is mediated by local microflora. It
      has been reported in some studies that even though beer contains small amounts of
      hops and its preparations, these compounds may affect the functioning of the
      human body. IXN exhibits an antiproliferative activity against human cell lines
      typical for breast cancer (MCF-7), ovarian cancer (A-2780), prostate cancer
      (DU145 and PC-3), and colon cancer (HT-29 and SW620) cells. It strongly inhibits
      the activation of the following carcinogens: 2-amino-3-methylimidazol-[4,5
      f]quinoline and aflatoxin B1 (AFB1) via human cytochrome P450 (CYP1A2). It also
      inhibits the production of prostate specific antigen (PSA). IXN significantly
      reduces the expression of transforming growth factor-beta (TGF-beta) in the case
      of invasive breast cancer MDA-MB-231. It interferes with JAK/STAT signaling
      pathway and inhibits the expression of pro1inflammatory genes in the monoblastic
      leukemia cell line (MonoMac6). It activates apoptosis in human umbilical vein
      endothelial cells (HUVEC) and human aortic smooth muscle cells (HASMCs). In
      addition, IXN shows an antiviral activity towards herpes viruses (HSV1 and HSV2)
      and bovine viral diarrhea virus (BVDV). 

PMID- 25771122
TI  - Three pairs of diastereoisomeric flavanone glycosides from Viscum articulatum.
AB  - Phytochemical examination of the leaves and stems of Viscum articulatum resulted
      in the isolation of three pairs of new flavanone glycosides, 2R/2S-viscarticulide
      A-C (1a/1b-3a/3b), together with eight known compounds (7-14). Their structures
      were established by extensive spectroscopic data analyses. The diastereoisomers
      were separated by HPLC on a chiral phase and the absolute configuration at C-2
      was determined by circular dichroism (CD) spectra. The protective effects of
      compounds 1-3 against H2O2-induced cytotoxicity with EA.hy926 cells were tested.
      The results showed that compounds 1-3 improved the survival of EA.hy926 cells
      after H2O2 exposure at the tested concentrations.

PMID- 25771123
TI  - Trinorcassane and cassane diterpenoids from the seeds of Caesalpinia minax.
AB  - An unprecedented trinorcassane diterpenoid and a cassane furanoditerpenoid were
      isolated from the seeds of Caesalpinia minax. It is the first example of dicylic
      cassane-type trinorditerpenoid, which is different from reported 16- or 17
      norcassane diterpenoids. The structure of the compounds was elucidated on the
      basis of 1D and 2D NMR analysis. Biosynthesis pathways are postulated, and this
      pathway was supported by semi-synthesis.

PMID- 25771124
TI  - A catechin-enriched green tea extract prevents glucose-induced survival reduction
      in Caenorhabditis elegans through sir-2.1 and uba-1 dependent hormesis.
AB  - Hyperglycemia is a hallmark of diabetes mellitus which leads to the onset of
      complications in the long term. Green tea through its high content of
      polyphenolic catechins, on the other hand, is suggested to prevent or at least
      delay such detrimental complications. In the present study we fed the nematode
      Caenorhabditis elegans on a liquid medium supplemented with 10mM glucose in the
      absence or presence of a catechin-enriched green tea extract (CEGTE). After
      exposure of young adults for 48h survival was subsequently measured under heat
      stress at 37 degrees C. Whereas CEGTE at 0.01% did not affect the survival of
      wild type nematodes, it completely reversed the glucose-induced survival
      reduction. Those effects were not achieved through the monomeric catechins
      included in CEGTE. RNA interference (RNAi) for sir-2.1 not only prevented the
      survival extension by CEGTE under simultaneous glucose exposure but also caused a
      further reduction of survival. Likewise, the knockdown of uba-1, encoding the
      only E1-ubiquitin-activating enzyme in C. elegans, proved that UBA-1 is essential
      for the survival extension by CEGTE and that its loss of function changes CEGTE
      from a survival extending into a survival reducing extract. Stimulation of the
      proteasome by CEGTE was finally proven through measurements of the proteolytic
      cleavage of a fluorogenic peptide substrate. To conclude, our studies provide
      evidence that CEGTE reverses glucose-induced damage in C. elegans through
      activation of adaptive responses mediated by SIR-2.1 and proteasomal degradation.
      The hormetic mode of action is revealed by a reduction of survival once the
      adaptive processes were blocked.

PMID- 25771125
TI  - Gender-specific increase in susceptibility to metabolic syndrome of offspring
      rats after prenatal caffeine exposure with post-weaning high-fat diet.
AB  - Prenatal caffeine exposure (PCE) alters the hypothalamic-pituitary-adrenocortical
      (HPA) axis-associated neuroendocrine metabolic programming and induces an
      increased susceptibility to metabolic syndrome (MS) in intrauterine growth
      retardation (IUGR) offspring rats. High-fat diet (HFD) is one of the main
      environmental factors accounting for the incidence of MS. In this study, we aimed
      to clarify the gender-specific increase in susceptibility to MS in offspring rats
      after PCE with post-weaning HFD. Maternal Wistar rats were administered with
      caffeine (120mg/kg.d) from gestational day 11 until delivery. The offspring rats
      with normal diet or HFD were euthanized at postnatal week 24, and blood samples
      were collected. Results showed that PCE not only reduced serum
      adrenocorticotropic hormone (ACTH) and corticosterone levels, but also enhanced
      serum glucose, triglyceride and total cholesterol (TCH) concentrations in the
      offspring rats. Moreover, several interactions among PCE, HFD and gender were
      observed by a three-way ANOVA analysis. In PCE offspring, HFD could aggravate the
      degree of increased serum triglyceride level. Meanwhile, serum corticosterone
      levels of females were decreased more obviously than those of males in PCE
      offspring. The results also revealed interactions between HFD and gender in the
      levels of serum ACTH, triglyceride and TCH, which were changed more evidently in
      female HFD offspring. These results indicate that HFD could exacerbate the
      dysfunction of lipid metabolism and the susceptibility to MS induced by PCE, and
      the female offspring are more sensitive to HFD-induced neuroendocrine metabolic
      dysfunction than their male counterparts.

PMID- 25771126
TI  - Environmental exposure to lead induces oxidative stress and modulates the
      function of the antioxidant defense system and the immune system in the semen of
      males with normal semen profile.
AB  - We investigated the associations between environmental exposure to lead and a
      repertoire of cytokines in seminal plasma of males with normal semen profile
      according to the WHO criteria. Based on the median lead concentration in seminal
      plasma, 65 samples were divided into two groups: low (LE) and high exposure to
      lead (HE). Differences in semen volume and the pH, count, motility and morphology
      of sperm cells were not observed between the examined groups. The total oxidant
      status value and the level of protein sulfhydryl groups as well as the activities
      of manganese superoxide dismutase and catalase were significantly higher in the
      HE group, whereas the total antioxidant capacity value and the activities of
      glutathione reductase and glutathione-S-transferase were depressed. IL-7, IL-10,
      IL-12, and TNF-alpha levels were significantly higher in the HE group compared
      with the LE group. Environmental exposure to lead is sufficient to induce
      oxidative stress in seminal plasma and to modulate antioxidant defense system.

PMID- 25771127
TI  - Boldine enhances bile production in rats via osmotic and farnesoid X receptor
      dependent mechanisms.
AB  - Boldine, the major alkaloid from the Chilean Boldo tree, is used in traditional
      medicine to support bile production, but evidence to support this function is
      controversial. We analyzed the choleretic potential of boldine, including its
      molecular background. The acute- and long-term effects of boldine were evaluated
      in rats either during intravenous infusion or after 28-day oral treatment.
      Infusion of boldine instantly increased the bile flow 1.4-fold in healthy rats as
      well as in animals with Mrp2 deficiency or ethinylestradiol induced cholestasis.
      This effect was not associated with a corresponding increase in bile acid or
      glutathione biliary excretion, indicating that the effect is not related to
      stimulation of either bile acid dependent or independent mechanisms of bile
      formation and points to the osmotic activity of boldine itself. We subsequently
      analyzed bile production under conditions of changing biliary excretion of
      boldine after bolus intravenous administration and found strong correlations
      between both parameters. HPLC analysis showed that bile concentrations of boldine
      above 10 MUM were required for induction of choleresis. Importantly, long-term
      pretreatment, when the bile collection study was performed 24-h after the last
      administration of boldine, also accelerated bile formation despite undetectable
      levels of the compound in bile. The effect paralleled upregulation of the Bsep
      transporter and increased biliary clearance of its substrates, bile acids. We
      consequently confirmed the ability of boldine to stimulate the Bsep
      transcriptional regulator, FXR receptor. In conclusion, our study clarified the
      mechanisms and circumstances surrounding the choleretic activity of boldine.

PMID- 25771128
TI  - The adverse effects of aldrin and dieldrin on both myometrial contractions and
      the secretory functions of bovine ovaries and uterus in vitro.
AB  - Aldrin and dieldrin are chloroorganic insecticides which are recognised as
      endocrine disruptors. The aim of the study was to investigate their effect on the
      secretory functions of the uterus and ovary and on myometrial contractions.
      Myometrial strips and uterine and ovarian cells from nonpregnant cows were
      incubated with the xenobiotics (0.1, 1 or 10 ng/ml) for 24 or 72 h. Next, their
      effect on viability of myometrial, endometrial, granulosa and luteal cells,
      myometrial strip contractions, the synthesis and secretion of prostaglandins
      (PGs: PGF2alpha and PGE2) from uterine cells, the secretion of oestradiol (E2),
      testosterone (T) and oxytocin (OT) from granulosa cells and the secretion of
      progesterone (P4) and OT from luteal cells were determined. Neither of the
      xenobiotics (10 ng/ml) affected (P>0.05) the viability of the ovarian and uterine
      cells, while both (0.1-10 ng/ml) decreased (P<0.05) the basal and OT-stimulated
      myometrial contractions. In spite of these effects, neither of the insecticides
      affected (P>0.05) the synthesis and the secretion of PGs from the myometrial
      cells. Although they also did not impair the secretion of the PGs from the
      endometrial cells, they abolished (P<0.05) the stimulatory effect of OT (P<0.05)
      on the secretion of the PGs and stimulated (P<0.05) the secretion of OT from the
      granulosa and luteal cells. Moreover, aldrin and dieldrin stimulated secretion of
      E2 and T from the granulosa cells, while only dieldrin increased (P<0.05) the
      secretion of P4 from luteal cells. The data show that aldrin and dieldrin
      stimulated the secretory function of the cultured granulosa and luteal cells and
      inhibited the myometrial contractions of cows in vitro, which may affect on
      natural parturition.

PMID- 25771129
TI  - Antenatal exposure to the selective serotonin reuptake inhibitor fluoxetine leads
      to postnatal metabolic and endocrine changes associated with type 2 diabetes in
      Wistar rats.
AB  - HYPOTHESIS: 10-15% of women take antidepressant medications during pregnancy. A
      recent clinical study reported that the use of selective serotonin reuptake
      inhibitor antidepressants during pregnancy is linked with an increased risk of
      postnatal obesity. While obesity is often associated with fatty liver,
      dyslipidemia and inflammation, to date, the effects of perinatal exposure to
      SSRIs on these outcomes are unknown. METHODS: Female nulliparous Wistar rats were
      given vehicle (N=15) or fluoxetine hydrochloride (FLX 10mg/kg/d; N=15) orally for
      2 weeks prior to mating until weaning. We assessed glucometabolic changes and
      hepatic pathophysiology in the offspring. RESULTS: Fluoxetine exposed offspring
      demonstrated altered glucose homeostasis without any alterations to beta cell
      mass. FLX-exposed offspring had a significant increase in the number of offspring
      with mild to moderate NASH and dyslipidemia. There was also increased
      inflammation of the liver in FLX-exposed offspring; males had significant
      elevations in TNFalpha, IL6 and monocyte chemoattractant protein 1 (MCP1), while
      female offspring had higher expression of TNFalpha, and increased macrophage
      infiltration (MCP1). LIMITATIONS: This is an animal study. Further research
      examining the metabolic outcomes of children exposed to antidepressants in utero
      are required, given the increase in childhood obesity and psychiatric medication
      use during pregnancy. CONCLUSION: These data demonstrate that fetal and neonatal
      exposure to FLX results in evidence of increased adiposity, fatty liver and
      abnormal glycemic control. Since these are all hallmarks of the metabolic
      syndrome, this raises concerns regarding the long term metabolic sequelae of
      fetal exposure to SSRIs in human populations.

PMID- 25771130
TI  - The effects of in utero bisphenol A exposure on reproductive capacity in several
      generations of mice.
AB  - In utero bisphenol A (BPA) exposure affects reproductive function in the first
      generation (F1) of mice; however, not many studies have examined the reproductive
      effects of BPA exposure on subsequent generations. In this study, pregnant mice
      (F0) were orally dosed with vehicle, BPA (0.5, 20, and 50 MUg/kg/day) or
      diethylstilbestrol (DES; 0.05 MUg/kg/day) daily from gestation day 11 until
      birth. F1 females were used to generate the F2 generation, and F2 females were
      used to generate the F3 generation. Breeding studies at the ages of 3, 6, and 9
      months were conducted to evaluate reproductive capacity over time. Further,
      studies were conducted to evaluate pubertal onset, litter size, and percentage of
      dead pups; and to calculate pregnancy rate, and mating, fertility, and
      gestational indices. The results indicate that BPA exposure (0.5 and 50
      MUg/kg/day) significantly delayed the age at vaginal opening in the F3 generation
      compared to vehicle control. Both DES (0.05 MUg/kg/day) and BPA (50 MUg/kg/day)
      significantly delayed the age at first estrus in the F3 generation compared to
      vehicle control. BPA exposure reduced gestational index in the F1 and F2
      generations compared to control. Further, BPA exposure (0.5 MUg/kg/day)
      compromised the fertility index in the F3 generation compared to control.
      Finally, in utero BPA exposure reduced the ability of female mice to maintain
      pregnancies as they aged. Collectively, these data suggest that BPA exposure
      affects reproductive function in female mice and that some effects may be
      transgenerational in nature.

PMID- 25771131
TI  - Biliary dyskinesia: a surgical disease rarely found outside the United States.
AB  - BACKGROUND: Our objective was to determine if cholecystectomy for biliary
      dyskinesia (BD) was performed more commonly in the United States than in 4
      comparator countries around the world. METHODS: Using the Nationwide Inpatient
      Sample, we extracted and analyzed data for cholecystectomy from 1991 to 2011
      using ICD-9 (International Classification of Diseases 9th Revision) procedure
      codes. To derive the number of cholecystectomies performed for BD, we used the
      ICD-9 code 575.8, greater than 80% of which are patients with BD. The same or
      equivalent code was used for the international comparator group. Through a
      SURGINET query we obtained data from verifiable national databases in 4 developed
      countries including the Swedish quality registry for surgical treatments of
      gallstone-related conditions (GallRiks), the Norwegian Cholecystectomy Registry,
      the Australian Bureau of Statistics, and the Polish National Health Insurance
      Agency. RESULTS: In the years ranging from 2008 to 2011, the number of
      cholecystectomies for BD per 1,000,000 population per year was less than 25 in
      the 4 comparator countries and greater than 85 in the United States (P < .01).
      From 1991 to 2011, the number of cholecystectomies for BD in the United States
      significantly increased from 43.3 to 89.1 per 1,000,000 population (P < .01).
      CONCLUSIONS: These data strongly suggest that cholecystectomy for BD is over
      utilized in the United States. In addition, this trend continues to increase in
      frequency.

PMID- 25771132
TI  - Improving ultrasound quality to reduce computed tomography use in pediatric
      appendicitis: the Safe and Sound campaign.
AB  - BACKGROUND: Safety concerns about the use of radiation-based imaging such as
      computed tomography (CT) in children have resulted in national recommendations to
      use ultrasound (US) for the diagnosis of appendicitis when possible. We evaluated
      the trends in CT and US use in a statewide sample and the accuracy of these
      modalities. METHODS: Patients less than or equal to 18 years undergoing
      appendectomy in Washington State from 2008 to 2013 were evaluated for
      preoperative US/CT use, as well as imaging/pathology concordance using data from
      the Surgical Care and Outcomes Assessment Program. RESULTS: Among 3,353 children,
      98.3% underwent preoperative imaging. There was a significant increase in the use
      of US first over the study period (P < .001). The use of CT at any time during
      the evaluation decreased. Despite this, in 2013, over 40% of the children still
      underwent CT imaging. Concordance between US imaging and pathology varied between
      40% and 75% at hospitals performing greater than or equal to 10 appendectomies in
      2013. Over one third (34.9%) of CT scans performed in the evaluation of children
      with appendicitis were performed after an indeterminate US. CONCLUSIONS: Although
      the use of US as the first imaging modality to diagnose pediatric appendicitis
      has increased over the past 5 years, over 40% of children still undergo a CT scan
      during their preoperative evaluation. Causality for this persistence of CT use is
      unclear, but could include variability in US accuracy, lack of training, and lack
      of awareness of the risks of radiation-based imaging. Developing a campaign to
      focus on continued reduction in CT and increased use of high-quality US should be
      pursued.

PMID- 25771133
TI  - Psychosocial problems in adolescents associated with frequent health care use.
AB  - BACKGROUND: The prevalence of somatic, mental and behavioural problems increases
      in puberty. Nevertheless, compared to adults, health service utilization by
      adolescents, and associated factors such as risky health behaviours, have been
      poorly explored. In order to improve health care services, there is a need for
      further research on adolescents frequently using primary health care. OBJECTIVES:
      We aimed to investigate adolescents who seek help for health issues, and examine
      whether particular socio-economic or psychological factors predict frequent
      primary health care use. METHODS: Finnish adolescents aged 13-18 years (N = 793)
      attending comprehensive, upper secondary and vocational schools participated in
      the study in 2005. Data were collected using a questionnaire that included the
      Youth Self Report (YSR), as well as questions on the psychosocial background of
      the adolescents and substance use. Data regarding the frequency of use of health
      services were gathered from medical records of the local public health care
      services. RESULTS: Altogether, 288 in the sample had used primary health care
      services making a combined total of 1411 health care visits. Female gender
      associated with frequent primary health care use. Furthermore, a high level of
      alcohol consumption and mental health symptoms in girls, and increased self
      reported somatic complaints in the YSR in boys were associated with frequent
      primary health care use. Attending upper secondary school was related to less
      frequent primary health care use. CONCLUSION: Few adolescents frequently use
      primary health care, but they account for a considerable proportion of all
      adolescent health care visits. There are higher levels of alcohol consumption, as
      well as socio-economic, educational and gender differences among adolescent
      frequent primary health care users.

PMID- 25771134
TI  - Restoration of obliterated engraved marks on steel surfaces by chemical etching
      reagent.
AB  - Chemical etching technique is widely used for restoration of obliterated engraved
      marks on steel surface in the field of public security. The consumed thickness of
      steel surface during restoration process is considered as a major criterion for
      evaluating the efficiency of the chemical etching reagent. The thinner the
      consumed thickness, the higher the restoration efficiency. According to chemical
      principles, maintaining the continuous oxidative capabilities of etching reagents
      and increasing the kinetic rate difference of the reaction between the engraved
      and non-engraved area with the chemical etching reagent can effectively reduce
      the consumed steel thickness. The study employed steel surface from the engine
      case of motorcycle and the car frame of automobile. The chemical etching reagents
      are composed of nitric acid as the oxidizer, hydrofluoric acid as the
      coordination agent and mixed with glacial acetic acid or acetone as the solvents.
      Based on the performance evaluation of three different etching reagents, the one
      composed of HNO3, HF and acetone gave the best result. 

PMID- 25771135
TI  - Outcomes of cataract surgery in eyes with previous herpes zoster ophthalmicus.
AB  - PURPOSE: To report the outcomes of cataract surgery in eyes with previous herpes
      zoster ophthalmicus (HZO). SETTING: Kellogg Eye Center, University of Michigan,
      Ann Arbor, Michigan, USA. DESIGN: Retrospective case series. METHODS: Eyes with a
      history of HZO that had phacoemulsification and intraocular lens implantation
      were reviewed. The information analyzed included the ophthalmologic history,
      visual acuity, preoperative and postoperative adjunct treatments, and
      complications. Analysis of the mean corrected distance visual acuity (CDVA) at 1
      month, 1 year, and the last follow-up was performed. RESULTS: Twenty-four eyes
      were evaluated. The mean CDVA improved from 20/112 (0.75 logMAR +/- 0.63 [SD])
      preoperatively to 20/53 (0.42 +/- 0.56 logMAR) 1 month postoperatively (P = .007)
      and 20/44 (0.34 +/- 0.55 logMAR) at 1 year (P = .052) but decreased to 20/71
      (0.55 +/- 0.72 logMAR) by last follow-up (P = .605 versus preoperative CDVA).
      Eleven patients (45.8%) had recurrent keratouveitis after the first episode, 5
      before cataract surgery and 6 after cataract surgery. Three had penetrating
      keratoplasty for worsening corneal opacification. Two patients had tractional
      retinal detachment from chronic uveitis and required vitrectomy and retinal
      repair. CONCLUSIONS: Visual recovery after cataract surgery in HZO might be
      compromised by chronic factors such as ocular surface disease and keratouveitis.
      Despite long quiescent waiting periods before surgery and aggressive preoperative
      and postoperative maintenance therapy, visual improvement might be hindered by
      the inherent pathology associated with HZO. Nevertheless, with careful patient
      selection, reasonable visual improvement can be achieved. FINANCIAL DISCLOSURE:
      No author has a financial or proprietary interest in any material or method
      mentioned.

PMID- 25771137
TI  - That antibiotics does not destroy virus does not mean that it does not help a
      human having virus.
AB  - In the defending activity of the body there always is a fight against different
      bacteria. By helping against the bacteria, antibiotics lets the forces of the
      body be more oriented against the virus. 

PMID- 25771136
TI  - Antioxidant effects of liquorice (Glycyrrhiza uralensis) extract during aging of
      longissimus thoracis muscle in Tan sheep.
AB  - The study was conducted to investigate the potential of liquorice extract (LE)
      from Glycyrrhiza uralensis as a dietary supplement for sheep to improve
      antioxidant capacity of meat. Fifty Tan sheep were randomly allocated to five
      groups with LE supplementation at levels of 0, 1000, 2000, 3000 and 4000 mg/kg
      feed. After 120 days, the longissimus thoracis muscle was sampled and conditioned
      for 0, 2, 4, 6 and 8 days at 4  degrees C. The results revealed that LE scavenged
      free radical in a dose-response manner in vitro. Supplementation with LE in
      animal diet increased (P<0.05) antioxidant content and radical scavenging
      activity while it decreased (P<0.05) reactive oxygen species (ROS) and
      thiobarbituric acid reactive substance (TBARS) levels of meat. Dietary LE
      supplementation can improve antioxidant capacity of meat, and the optimum dosage
      range of LE supplementation appeared to be 3000 to 4000 mg/kg feed.

PMID- 25771138
TI  - Stimulation of the medial septum should benefit patients with temporal lobe
      epilepsy.
AB  - Electrical stimulation of the septal nuclei via deep brain stimulating electrodes
      is proposed as a potentially beneficial therapy for medication-resistant temporal
      lobe epilepsy. In a multicenter study, stimulation of anterior thalamus was shown
      to reduce numbers of seizures, but decrease was only in the range of 40%. This
      might be improved with septal stimulation, which has strong and direct reciprocal
      connections with the hippocampal formation, the structure most involved in
      temporal lobe epilepsy. Medial septal neurons drive a 3-12 Hz theta rhythm in
      hippocampus of rodents. Theta rhythm is less obvious in human hippocampus, but it
      is present and it varies with cognitive tasks. The hippocampal theta rhythm is
      disrupted by seizures. In animal models, restoration of theta by sensory
      stimulation, septal electrical stimulation or cholinergic drugs infused into
      septum ameliorates seizures. Seizure activity in hippocampus is faithfully
      reflected in septal nuclei, and septum sometimes leads the seizure activity. A
      subset of patients with temporal lobe epilepsy have structural enlargement of
      their septal nuclei. At high levels of intensity, septal stimulation is
      subjectively pleasurable and strongly reinforcing. Rats will repeatedly press a
      bar to stimulate their septum. Initial experience with human septal stimulation
      in the 1950s was not favorable, with ineffective therapy for schizophrenia and a
      high rate of surgical complications. Subsequent experience in 50-100 pain
      patients employing modern neurosurgical techniques was more favorable and
      demonstrated septal stimulation to be safe and tolerable. The current state of
      knowledge is sufficient to consider design of a clinical trial of medial septal
      stimulation in selected patients with medication-resistant temporal lobe
      epilepsy.

PMID- 25771139
TI  - Cyclic fatigue resistance of 3 different nickel-titanium reciprocating
      instruments in artificial canals.
AB  - INTRODUCTION: The purpose of this study was to evaluate the cyclic fatigue
      resistance of 3 different nickel-titanium reciprocating instruments. METHODS: A
      total of 45 nickel-titanium instruments were tested and divided into 3
      experimental groups (n = 15): group 1, WaveOne Primary instruments; group 2,
      Reciproc R25 instruments; and group 3, Twisted File (TF) Adaptive M-L1
      instruments. The instruments were then subjected to cyclic fatigue test on a
      static model consisting of a metal block with a simulated canal with 60 degrees 
      angle of curvature and a 5-mm radius of curvature. WaveOne Primary, Reciproc R25,
      and TF Adaptive instruments were activated by using their proprietary movements,
      WaveOne ALL, Reciproc ALL, and TF Adaptive, respectively. All instruments were
      activated until fracture occurred, and the time to fracture was recorded visually
      for each file with a 1/100-second chronometer. Mean number of cycles to failure
      and standard deviations were calculated for each group, and data were
      statistically analyzed (P < .05). Instruments were also observed through scanning
      electron microscopy to evaluate type of fracture. RESULTS: Cyclic fatigue
      resistance of Reciproc R25 and TF Adaptive M-L1 was significantly higher than
      that of WaveOne Primary (P = .009 and P = .002, respectively). The results showed
      no statistically significant difference between TF Adaptive M-L1 and Reciproc R25
      (P = .686). Analysis of the fractured portion under scanning electron microscopy
      indicated that all instruments showed morphologic characteristics of ductile
      fracture that were due to accumulation of metal fatigue. CONCLUSIONS: No
      statistically significant differences were found between the instruments tested
      except for WaveOne Primary, which showed the lowest resistance to cyclic fatigue.

PMID- 25771140
TI  - Differential Proteinase Patterns among Candida albicans Strains Isolated from
      Root Canal and Lingual Dorsum: Possible Roles in Periapical Disease.
AB  - INTRODUCTION: Proteinases play pivotal roles in Candida albicans infections.
      Although the yeast can colonize the pulpal environment, there is no information
      about the enzymatic profile of this organism. This in vitro study aimed to
      determine the proteolysis levels and to investigate differences in the expression
      of aspartyl proteinase genes (Sap 1, Sap 2, and Sap 4) among various root canal
      strains and clinical isolates from the lingual dorsum. METHODS: The extracellular
      proteinase activity of 104 C. albicans samples isolated from the lingual dorsum
      and from necrotic root canals was measured with respect to bovine serum albumin
      degradation after 5 days of incubation at 37 degrees C. We used reverse
      transcription polymerase chain reaction, a highly sensitive method, to detect
      messenger RNA transcripts of aspartyl proteinase genes (Sap 1, Sap 2, and Sap 4).
      The C. albicans strain SC 5314 was used as a positive control for both
      experiments because it is recognized as being highly proteolytic. All tests were
      performed in triplicate. RESULTS: Regardless of the isolation site, all C.
      albicans strains produced an opaque precipitation halo around the colonies,
      indicating some proteinase activity. However, the production of proteinase on the
      plates was significantly greater (P < .05) by the endodontic samples. Sap 2 was
      the most commonly expressed gene in all samples. Among the root canal samples,
      the detection of Sap 1 transcripts was always associated with the expression of
      Sap 2 and Sap 4. Sap 4 gene expression was detected in all root canal samples.
      The simultaneous expression of the 3 investigated Sap genes (Sap 1, Sap 2, and
      Sap 4) was more common in strains isolated from the lingual dorsum (50%) than in
      those isolated from root canals (29.4%). CONCLUSIONS: The increased proteolytic
      activity as well as the distinct pattern of Sap expression observed among the
      root canal samples may suggest a pathogenic role for C. albicans in endodontic
      infections.

PMID- 25771141
TI  - Proinflammatory Activity of Primarily Infected Endodontic Content against
      Macrophages after Different Phases of the Root Canal Therapy.
AB  - INTRODUCTION: This study investigated the presence of target bacterial species
      and the levels of endotoxins in teeth with apical periodontitis. Levels of
      inflammatory mediators (interleukin [IL]-1beta and tumor necrosis factor [TNF]
      alpha) were determined after macrophage stimulation with endodontic content after
      different phases of endodontic therapy using different irrigants. METHODS: Thirty
      primarily infected root canals were randomly assigned into 3 groups according to
      the irrigant used for root canal preparation (n = 10 per group): GI: 2.5% sodium
      hypochlorite, GII: 2% chlorhexidine gel, and GIII (control group): saline
      solution. Root canal samples were taken by using paper points before (s1) and
      after root canal instrumentation (s2), subsequently to 17% EDTA (s3), after 30
      days of intracanal medication (Ca[OH]2 + saline solution) (s4), and before root
      canal obturation (s5). Polymerase chain reaction (16S recombinant DNA) and
      limulus amebocyte lysate assay were used for bacterial and endotoxin detection,
      respectively. Macrophages were stimulated with the root canal contents for IL
      1beta/TNF-alpha measurement using enzyme-linked immunosorbent assay. RESULTS:
      Porphyromonas gingivalis (17/30), Porphyromonas endodontalis (15/30), and
      Prevotella nigrescens (11/30) were the most prevalent bacterial species. At s1,
      endotoxins were detected in 100% of the root canals (median = 32.43 EU/mL). In
      parallel, substantial amounts of IL-1beta and TNF-alpha were produced by
      endodontic content-stimulated macrophages. At s2, a significant reduction in
      endotoxin levels was observed in all groups, with GI presenting the greatest
      reduction (P < .05). After a root canal rinse with EDTA (s3), intracanal
      medication (s4), and before root canal obturation (s5), endotoxin levels reduced
      without differences between groups (P < .05). IL-1beta and TNF-alpha release
      decreased proportionally to the levels of residual endotoxin (P < .05).
      CONCLUSIONS: Regardless of the use of sodium hypochlorite or CHX, the greatest
      endotoxin reduction occurs after chemomechanical preparation. Increasing steps of
      root canal therapy associated with intracanal medication enhances endotoxin
      reduction, leading to a progressively lower activation of proinflammatory cells
      such as macrophages.

PMID- 25771142
TI  - Too much or not enough of a good thing--The Janus faces of autophagy in cardiac
      fuel and protein homeostasis.
AB  - Cells respond to changes in their environment and in their intracellular milieu
      by altering specific pathways of protein synthesis and degradation. Autophagy is
      a highly conserved catabolic process involved in the degradation of long-lived
      proteins, damaged organelles, and subcellular structures. The process is
      orchestrated by the autophagy related protein (Atg) to form the double-membrane
      structure autophagosomes, which then fuse with lysosomes to generate
      autophagolysosomes where subcellular contents are degraded for a variety of
      cellular processes. Alterations in autophagy play an important role in diseases
      including cancer, neurodegenerative diseases, aging, metabolic diseases,
      inflammation and cardiovascular diseases. In the latter, dysregulated autophagy
      is speculated to contribute to the onset and development of atherosclerosis,
      ischemia/reperfusion injury, cardiomyopathy, diabetes mellitus, and hypertension.
      Autophagy may be both adaptive and beneficial for cell survival, or maladaptive
      and detrimental for the cell. Basal autophagy plays an essential role in the
      maintenance of cellular homeostasis whereas excessive autophagy may lead to
      autophagic cell death. The point and counterpoint discussion highlights adaptive
      vs. maladaptive autophagy. In this review, we discuss the molecular control of
      autophagy, focusing particularly on the regulation of physiologic vs. defective
      autophagy. 

PMID- 25771143
TI  - Rosuvastatin suppresses atrial tachycardia-induced cellular remodeling via
      Akt/Nrf2/heme oxygenase-1 pathway.
AB  - Atrial fibrillation (AF) is associated with structural remodeling in atrial
      myocytes. Emerging evidence suggests that statin has a protective effect on AF
      through cholesterol-independent mechanisms. The aim of this study is to
      investigate whether heme oxygenase-1 (HO-1), a potent antioxidant system,
      mediates the suppressive effect of statin on atrial tachycardia-induced
      structural remodeling. Treatment of cultured atrium-derived myocytes (HL-1 cell
      line) with rosuvastatin enhanced HO-1 expression/activity and attenuated
      tachypacing-induced oxidative stress and myofibril degradation. Heme oxygenase-1
      inhibitors and small-interfering RNA for HO-1 blocked the inhibitory effect of
      rosuvastatin on tachypacing-stimulated changes, suggesting the crucial role of HO
      1 in mediating the effect of rosuvastatin. Time-dependent experiments and loss-of
      function study demonstrated that Akt/Nrf2 pathways lay to the up-stream of HO-1
      in this signaling cascade. Furthermore, the involvement of Akt/Nrf2/HO-1 pathway
      in the antioxidant effect of rosuvastatin was documented in an ex vivo
      tachypacing model. The suppressive effect of statin on atrial tachypacing-induced
      cellular remodeling is mediated via the activation of Akt/Nrf2/HO-1 signaling,
      which provides a possible explanation for the protective effect of statin on AF. 

PMID- 25771145
TI  - Response to "Comment to the article 'A systematic analysis of neonatal mouse
      heart regeneration after apical resection'".

PMID- 25771144
TI  - A novel phosphorylation site, Serine 199, in the C-terminus of cardiac troponin I
      regulates calcium sensitivity and susceptibility to calpain-induced proteolysis.
AB  - Phosphorylation of cardiac troponin I (cTnI) by protein kinase C (PKC) is
      implicated in cardiac dysfunction. Recently, Serine 199 (Ser199) was identified
      as a target for PKC phosphorylation and increased Ser199 phosphorylation occurs
      in end-stage failing compared with non-failing human myocardium. The functional
      consequences of cTnI-Ser199 phosphorylation in the heart are unknown. Therefore,
      we investigated the impact of phosphorylation of cTnI-Ser199 on myofilament
      function in human cardiac tissue and the susceptibility of cTnI to proteolysis.
      cTnI-Ser199 was replaced by aspartic acid (199D) or alanine (199A) to mimic
      phosphorylation and dephosphorylation, respectively, with recombinant wild-type
      (Wt) cTn as a negative control. Force development was measured at various
      [Ca(2+)] and at sarcomere lengths of 1.8 and 2.2 MUm in demembranated
      cardiomyocytes in which endogenous cTn complex was exchanged with the recombinant
      human cTn complexes. In idiopathic dilated cardiomyopathy samples, myofilament
      Ca(2+)-sensitivity (pCa50) at 2.2 MUm was significantly higher in 199D (pCa50 =
      5.79 +/- 0.01) compared to 199A (pCa50 = 5.65 +/- 0.01) and Wt (pCa50 = 5.66 +/-
      0.02) at ~63% cTn exchange. Myofilament Ca(2+)-sensitivity was significantly
      higher even with only 5.9 +/- 2.5% 199D exchange compared to 199A, and saturated
      at 12.3 +/- 2.6% 199D exchange. Ser199 pseudo-phosphorylation decreased cTnI
      binding to both actin and actin-tropomyosin. Moreover, altered susceptibility of
      cTnI to proteolysis by calpain I was found when Ser199 was pseudo-phosphorylated.
      Our data demonstrate that low levels of cTnI-Ser199 pseudo-phosphorylation (~6%)
      increase myofilament Ca(2+)-sensitivity in human cardiomyocytes, most likely by
      decreasing the binding affinity of cTnI for actin-tropomyosin. In addition, cTnI
      Ser199 pseudo-phosphorylation or mutation regulates calpain I mediated
      proteolysis of cTnI.

PMID- 25771146
TI  - Carbonic anhydrase XII in valve interstitial cells promotes the regression of
      calcific aortic valve stenosis.
AB  - AIMS: Calcific aortic valve stenosis (CAVS) is the most common heart valve
      disease. In the present work we sought to determine the reversibility of
      mineralization in the aortic valve. METHODS AND RESULTS: By using in vitro
      analyses we found that valve interstitial cells (VICs) have the ability to resorb
      minerals. We documented that agonist of P2Y2 receptor (P2Y2R) promoted the
      expression of carbonic anhydrase XII (CAXII) at the cell membrane of VICs,
      whereby minerals are resorbed. P2Y2R-mediated mineral resorption was corroborated
      by using mouse VICs isolated from wild type and P2Y2R(-/-) mice. Measurements of
      extracellular pH (pHe) by using core-shell nanosensors revealed that P2Y2R
      mediated CAXII export to the cell membrane led to an acidification of
      extracellular space, whereby minerals are resorbed. In vivo, we next treated
      LDLR(-/-)/ApoB(100/100)/IGF2 mice, which had developed CAVS under a high-fat/high
      sucrose diet for 8 months, with 2-thioUTP (a P2Y2R agonist) or saline for the
      next 2 months. The administration of 2-thioUTP (2mg/kg/day i.p.) reduced the
      mineral volume in the aortic valve measured with serial microCT analyses, which
      improved hemodynamics and reduced left ventricular hypertrophy (LVH). Examination
      of leaflets at necropsy confirmed a lower level of mineralization and fibrosis
      along with higher levels of CAXII in mice under 2-thioUTP. In another series of
      experiment, the administration of acetazolamide (a CA inhibitor) prevented the
      acidification of leaflets and the regression of CAVS induced by 2-thioUTP in
      LDLR(-/-)/ApoB(100/100)/IGF2 mice. CONCLUSION: P2Y2R-mediated expression of CAXII
      by VICs acidifies the extracellular space and promotes the regression of CAVS.

PMID- 25771147
TI  - Synthesis and characterization of fluoride-incorporated polyoxovanadates.
AB  - The speciation studies of oxovanadates are essential to clarify their biological
      activities. We surveyed the distribution of oxovanadate species in the presence
      of halide anions with various acid concentrations in an aqueous mixed-solvent
      system. The presence of chloride, bromide, and iodide anions has no effects on
      the appearance of polyoxovanadate species observed in (51)V NMR. Those are the
      precedent formation of metavanadate species and decavanadates. The presence of
      fluoride anion during the addition of acids exhibits strong intervention in the
      polyoxovanadate equilibria and we found the subsequent formation of two
      polyoxovanadate species by (51)V NMR observation. From the estimated experimental
      condition, we isolated fluoride-incorporated polyoxovanadates {Et4N}4[V7O19F] and
      {Et4N}4[HV11O29F2], successfully. Polyanion [V7O19F](4-) is the fluoride
      incorporated all V(V) state polyoxovanadate which has two different coordination
      environments of tetrahedral and square pyramidal vanadium units within the one
      anionic structural integrity. The structural gap between tetrahedral-unit-based
      metavanadate and octahedral-unit-based decavanadate structures may be linked by
      this hybrid complex. 

PMID- 25771148
TI  - N-acetylcysteine prevents behavioral and biochemical changes induced by alcohol
      cessation in rats.
AB  - N-acetylcysteine (NAC), a glutamate-modulating agent with antioxidant and anti
      inflammatory properties, has been considered as a potential anti-addictive drug.
      Beneficial effects were reported for cocaine, cannabis, and tobacco addicts, but
      the effect of NAC in alcoholics or in alcohol animal models is unknown. The
      aggravation of alcohol withdrawal symptoms, such as anxiety, has been associated
      with increased levels of serum corticosterone and leptin. Thus, the aim of this
      study was to assess the effects of NAC on anxiety, as well as corticosterone and
      leptin serum levels, after cessation of chronic alcohol treatment in rats. Male
      Wistar rats were treated with 2 g/kg ethanol, twice daily, by gavage for 30 days;
      control animals received an appropriate dose of glucose to balance caloric
      intake. Rats were treated for 4 days with NAC (60 and 90 mg/kg, intra
      peritoneally [i.p.]) or saline after alcohol cessation. Twenty-four hours after
      the last treatment, rats were exposed to a 5-min session in the open-field test
      (OF). Corticosterone and leptin serum levels were determined by ELISA in samples
      collected within 30 min after the OF. Results showed that rats were hypoactive
      (decreased rearing, peripheral, and total crossings), and that corticosterone and
      leptin levels were increased 5 days after alcohol cessation. Four days of NAC
      prevented the behavioral and biochemical changes brought about by alcohol
      cessation. We suggest that, in addition to the anti-addictive properties reported
      for other drugs of abuse, NAC is potentially useful in the management of alcohol
      withdrawal.

PMID- 25771150
TI  - Weight-bearing asymmetry and vertical activity differences in a rat model of post
      traumatic knee osteoarthritis.
AB  - OBJECTIVE: This study used a rat model of post-traumatic knee osteoarthritis (OA)
      created by anterior cruciate ligament transection with partial medial
      meniscectomy (ACLT + pMMx). In this model, mild to moderate structural changes
      that are typical of knee OA have been observed within 2 and 8 weeks post-surgery.
      We aimed to determine whether pain-related behaviours can distinguish between an
      ACLT + pMMx and a sham surgery group. DESIGN: Three-month old male Sprague-Dawley
      rats underwent ACLT + pMMx on their right hindlimb within two groups of n = 6
      each, and sham surgery within two groups of n = 5 each. Assessments evaluated
      percent ipsilateral weight-bearing for static weight-bearing and 18 different
      variables of exploratory motor behaviour at multiple time points between 1 and 8
      weeks post-surgery. Histology was performed on the right hindlimbs at 4 and 8
      weeks post-surgery. RESULTS: Histology confirmed mild to moderate knee OA changes
      in the ACLT + pMMx group and the absence of knee OA changes in the sham group.
      Compared to the sham group, the ACLT + pMMx group had significantly lower percent
      ipsilateral weight-bearing from 1 through 8 weeks post-surgery. Compared to the
      sham group, the ACLT + pMMx group had significantly lower vertical activity
      (episode count, time, and count) values. CONCLUSIONS: These findings suggest that
      ipsilateral weight-bearing deficit and vertical activity limitations resulted
      from the presence of knee OA-like changes in this model. When using the ACLT +
      pMMx-induced rat model of knee OA, percent ipsilateral weight-bearing and
      vertical activity distinguished between rats with and without knee OA changes.
      These variables may be useful outcome measures in preclinical research performed
      with this experimental post-traumatic knee OA model.

PMID- 25771152
TI  - Drug management in the elderly adult with chronic kidney disease: a review for
      the primary care physician.
AB  - With advancing age, the functional reserve of many organs tends to decrease. In
      particular, the lean body mass, the levels of serum albumin, the blood flow to
      the liver, and the glomerular filtration rate are reduced in elderly individuals
      and can be further impaired by the concomitant presence of acute or chronic
      kidney disease. Moreover, patients with kidney disease are often affected by
      comorbid processes and are prescribed multiple medications. The aging process
      also modifies some drug interactions, including the affinity of some drugs for
      their receptor, the number of receptors, and the cell responses upon receptor
      activation. Therefore, older patients with kidney disease are particularly
      susceptible to the risks of adverse drug reactions. Planning a pharmacological
      regimen in such patients is confounded by the paucity of information available on
      the pharmacokinetic and pharmacodynamic profiles of a large number of drugs
      commonly used in this group of patients. Finally, many aged patients suffer from
      unintentional poor compliance. In this review, the problems physicians face in
      designing safe and effective medication management in elderly individuals are
      discussed, paying attention to those more frequently used, which may be
      potentially harmful in patients with kidney disease. The risks of overdosing and
      underdosing are outlined, and some recommendations to reduce the risk of adverse
      drug reactions are provided. A review of the literature covering the field of
      drug management in older patients with kidney disease was performed by selecting
      those articles published between January 1, 1990, and December 1, 2014, using
      PubMed as a search engine with the keywords elderly, kidney disease, drugs, drug
      interaction, and renal function. 

PMID- 25771151
TI  - Sodium selenate reduces hyperphosphorylated tau and improves outcomes after
      traumatic brain injury.
AB  - Traumatic brain injury is a common and serious neurodegenerative condition that
      lacks a pharmaceutical intervention to improve long-term outcome.
      Hyperphosphorylated tau is implicated in some of the consequences of traumatic
      brain injury and is a potential pharmacological target. Protein phosphatase 2A is
      a heterotrimeric protein that regulates key signalling pathways, and protein
      phosphatase 2A heterotrimers consisting of the PR55 B-subunit represent the major
      tau phosphatase in the brain. Here we investigated whether traumatic brain injury
      in rats and humans would induce changes in protein phosphatase 2A and
      phosphorylated tau, and whether treatment with sodium selenate-a potent PR55
      activator-would reduce phosphorylated tau and improve traumatic brain injury
      outcomes in rats. Ninety young adult male Long-Evans rats were administered
      either a fluid percussion injury or sham-injury. A proportion of rats were killed
      at 2, 24, and 72 h post-injury to assess acute changes in protein phosphatase 2A
      and tau. Other rats were given either sodium selenate or saline-vehicle treatment
      that was continuously administered via subcutaneous osmotic pump for 12 weeks.
      Serial magnetic resonance imaging was acquired prior to, and at 1, 4, and 12
      weeks post-injury to assess evolving structural brain damage and axonal injury.
      Behavioural impairments were assessed at 12 weeks post-injury. The results showed
      that traumatic brain injury in rats acutely reduced PR55 expression and protein
      phosphatase 2A activity, and increased the expression of phosphorylated tau and
      the ratio of phosphorylated tau to total tau. Similar findings were seen in post
      mortem brain samples from acute human traumatic brain injury patients, although
      many did not reach statistical significance. Continuous sodium selenate treatment
      for 12 weeks after sham or fluid percussion injury in rats increased protein
      phosphatase 2A activity and PR55 expression, and reduced the ratio of
      phosphorylated tau to total tau, attenuated brain damage, and improved
      behavioural outcomes in rats given a fluid percussion injury. Notably, total tau
      levels were decreased in rats 12 weeks after fluid percussion injury, and several
      other factors, including the use of anaesthetic, the length of recovery time, and
      that some brain injury and behavioural dysfunction still occurred in rats treated
      with sodium selenate must be considered in the interpretation of this study.
      However, taken together these data suggest protein phosphatase 2A and
      hyperphosphorylated tau may be involved in the neurodegenerative cascade of
      traumatic brain injury, and support the potential use of sodium selenate as a
      novel traumatic brain injury therapy. 

PMID- 25771153
TI  - Global analysis of genetic variations in a 56-bp variable number of tandem repeat
      polymorphisms within the human deoxyribonuclease I gene.
AB  - A 56-bp variable number of tandem repeat polymorphism is confirmed in intron 4 of
      the human deoxyribonuclease I (DNase I) gene (HumDN1). The purpose of the present
      study was to document global ethnic variations of allelic frequencies in HumDN1
      VNTR polymorphisms. In this study, HumDN1 VNTR polymorphisms in 11 worldwide
      populations were examined by polymerase chain reaction and compared with those
      reported previously. Fifteen genotypes were identified in these 11 populations.
      Novel genotypes were found: 1/2 was observed in Ghanaians and mestizos, 3/6 was
      in Tamangs, 4/6 was in Tibetans and Nahuas, 6/6 was in Sinhalese. The African
      population showed the highest frequency for the HumDN1(*)3 allele. Among Asian
      populations, the different genotype distribution was observed. The predominant
      allele in Mongolian, Korean, Japanese, and Chinese populations was HumDN1(*)3,
      followed by HumDN1(*)4, and then HumDN1(*)5. In Chinese from South China,
      Tamangs, and Sinhalese, HumDN1(*)4 and HumDN1(*)5 were predominant. The allele
      frequency for HumDN1(*)4 was high in three Mexican populations, but a significant
      difference was observed between Nahuas and Huicoles. Germans and Turks showed a
      similar distribution. This study is the first to show the existence of a certain
      genetic heterogeneity in the worldwide distribution of HumDN1 VNTR polymorphism. 

PMID- 25771154
TI  - Prognosis of adult asthma: a 7-year follow-up study.
AB  - BACKGROUND: Studies on adult-onset asthma and the contributing factors for its
      prognosis are few in the literature. OBJECTIVE: To evaluate asthma prognosis,
      remission rate, and contributing factors in an adult patient population. METHODS:
      Two hundred patients with a diagnosis of adult-onset asthma in 2006 were included
      in this study. Of these, 160 were contacted in 2013 and participated in the
      study. Their demographic features, family history, clinical symptoms, pulmonary
      function test results, and Asthma Control Test scores were re-evaluated.
      Patients' asthma control status was determined. Patients who had total control
      and had not used any asthma treatment for at least 2 years were classified as in
      remission. RESULTS: The study group consisted of 160 patients (144 women and 16
      men, mean age 52.9 +/- 10.3 years). Nearly 70% of patients had adult-onset asthma
      before 40 years of age. According to asthma control status, 21.9% of patients had
      uncontrolled asthma, 29.4% had partially controlled asthma, and 48.8% had totally
      controlled asthma. Remission was observed in 11.3% of the entire study group. The
      mean age of the remission group was significantly younger. Disease duration was
      shorter and the proportion of patients with atopy was larger in the totally
      controlled and remission groups. Except in the remission group, patients showed
      weight gain from 2006 through 2013. CONCLUSION: According to these 7-year follow
      up data, the remission rate of asthma was 11.3%. Patients with younger age,
      younger onset, atopy, allergic rhinitis, and few comorbidities seemed to have a
      greater possibility of remission.

PMID- 25771155
TI  - Validation of an ICD-9-based claims algorithm for identifying patients with
      chronic idiopathic/spontaneous urticaria.
AB  - BACKGROUND: There is no specific International Classification of Diseases, Ninth
      Revision, Clinical Modification (ICD-9-CM) code for chronic idiopathic urticaria
      or spontaneous urticaria (CIU/CSU), a skin condition characterized by hives and
      angioedema lasting at least 6 weeks with no known cause. OBJECTIVE: To validate
      an ICD-9-CM-based algorithm for identification of patients with CIU/CSU and thus
      facilitate claims-based research. METHODS: Patient records were reviewed at 4 US
      practices. Patients included in the study were from a random sample of those
      identified by their physician as having CIU/CSU or because they met the following
      diagnosis-based algorithm: (1) at least 2 outpatient ICD-9-CM diagnosis codes
      708.1, 708.8, or 708.9 at least 6 weeks apart or (2) 1 outpatient diagnosis of
      708.1, 708.8, or 708.9 and 1 diagnosis of 995.1 at least 6 weeks apart. Data
      collected included ICD-9-CM codes, diagnoses of urticaria and allergy-related
      conditions, and medication use. Sensitivity and positive predictive value were
      calculated. The study was approved by the Western Institutional Review Board.
      RESULTS: One hundred forty-nine patient records were reviewed (mean age 41.1
      years; 73.8% were women; 69.1% were white): 115 were identified with the
      diagnosis-based algorithm, 90 were patients with "known CIU/CSU", and 56 were in
      the 2 groups. The mean duration of CIU/CSU was 2.9 to 3.1 years. The 2 cohorts
      most frequently had diagnoses of idiopathic urticaria, unspecified urticaria, and
      other specified urticaria. The diagnosis-based algorithm had a positive
      predictive value of 90.4% and a sensitivity of 71.1%. CONCLUSION: The high
      positive predictive value suggests that patients identified using the algorithm
      are highly likely to have CIU/CSU. The 71.1% sensitivity suggests that most
      patients with CIU/CSU will be identified. The validation statistics support the
      use of the diagnosis-based algorithm in claims-based research, although future
      studies could refine the algorithm further.

PMID- 25771156
TI  - Management of pollen food and oral allergy syndrome by health care professionals
      in the United Kingdom.

PMID- 25771157
TI  - Vertical distribution of (137)Cs activity concentration in marine sediments at
      Amvrakikos Gulf, western of Greece.
AB  - The aim of the present work is the study of (137)Cs migration in sediment column
      taking into account the sedimentation rate in the Amvrakikos Gulf, at the western
      part of Greece. Marine core sediments were collected and the measurements were
      performed using the high resolution gamma-ray spectrometry method. The vertical
      distribution of (137)Cs activity concentration, as part of anthropogenic marine
      radioactivity, provided averaged sedimentation rate by identifying the depths of
      activity concentrations due to the Chernobyl accident and the nuclear tests
      signals. Furthermore, (137)Cs measurements were reproduced using the proposed one
      dimensional diffusion-advection model which provides mainly as an output, the
      sedimentation rate and the average diffusivity of (137)Cs in the sediment column.
      The proposed model estimates the temporal variation of (137)Cs activity
      concentration from 1987 (one year after the Chernobyl accident) till today
      (2014). 

PMID- 25771158
TI  - Women with epilepsy and post partum bleeding--Is there a role for vitamin K
      supplementation?
AB  - PURPOSE: Guidelines for women with epilepsy (WWE) are advising those on enzyme
      inducing drugs EIAEDs to take vitamin K the last month of pregnancy. The primary
      aim of this study was to investigate whether WWE have a higher frequency of large
      post partum hemorrhage. Secondary we wanted to see if this was more severe in
      women taking EIAEDs, and also to evaluate whether those receiving prenatal
      vitamin K supplementation have a less pronounced risk. METHODS: All patients
      (n=109), with the diagnosis of epilepsy giving birth at OUS Rikshospitalet from
      2006 to 2011 were selected to be in the epilepsy group. They were compared to
      controls with regard to the amount of post partum hemorrhage, gestational age for
      the mother, birth weight and APGAR score in the newborns. RESULTS: No significant
      difference between the groups regarding post partum hemorrhage, gestational age,
      birthweight or APGAR score in the newborn was found. Also, comparing the WWE
      using EIAED who received prenatal vitamin K with those who did not receive
      vitamin K, no significant difference in post partum hemorrhage could be
      demonstrated. CONCLUSION: In this study, WWE was not found to have increased risk
      of post partum hemmorrhage including those using EIAED with/without vitamin K
      supplementation.

PMID- 25771161
TI  - A decade of athlete ECG criteria: where we've come and where we're going.
AB  - Competitive athletes and highly active individuals commonly develop
      cardiovascular adaptations. Underlying features of exercise-induced cardiac
      remodeling often manifest as distinct patterns on the 12-lead electrocardiogram
      (ECG). Considerable effort has been directed toward defining the scope of ECG
      abnormalities in this population and numerous criteria have been proposed for the
      task of differentiating benign athletic ECG changes from patterns suggestive of
      underlying cardiovascular disease. This review will provide a historical overview
      of athlete ECG criteria development with a final emphasis on remaining areas of
      scientific and clinical uncertainty.

PMID- 25771159
TI  - Modulation of sphingolipid metabolism with calorie restriction enhances insulin
      action in skeletal muscle.
AB  - This study sought to investigate the effect of calorie restriction (CR) on
      skeletal muscle sphingolipid metabolism and its contribution to improved insulin
      action in rats after a 6-month feeding study. Twenty nine (29) male Fischer 344
      rats were randomized to an ad libitum (AL) diet or 30% CR. Dietary intake, body
      weight and insulin sensitivity were monitored. After 6 months, skeletal muscle
      (vastus lateralis) was obtained for insulin signaling and lipid profiling. CR
      significantly decreased insulin and glucose levels and also altered the
      expression and activity of proteins involved in sphingolipid formation and
      metabolism. The quantities of ceramides significantly increased in CR animals
      (P<.05; n=14-15), while ceramide metabolism products (i.e., glycosphingolipids:
      hexosylceramides and lactosylceramides) significantly decreased (P<.05; n=14-15).
      Ceramide phosphates, sphingomyelins, sphingosine and sphingosine phosphate were
      not significantly different between AL and CR groups (P=ns; n=14-15).
      Lactosylceramide quantities correlated significantly with surrogate markers of
      insulin resistance (homeostasis model of assessment on insulin resistance)
      (r=0.7; P<.005). Products of ceramide metabolism (glycosphingolipids), known to
      interfere with insulin signaling at elevated levels, were significantly reduced
      in the skeletal muscle of CR animals. The increase in insulin sensitivity is
      associated with glycosphingolipid levels. 

PMID- 25771160
TI  - [Ultrasonography as a tool in diagnosis of carpal tunnel syndrome].
AB  - OBJECTIVE: We aimed to determine the value of ultrasonography (US) in the
      diagnosis of carpal tunnel syndrome (CTS). METHODS: Two hundred patients (400
      hands) were submitted to wrist US to measure median nerve area (MNA), questioning
      on paresthesia and pain in the median nerve territory, Tinel and Phalen
      maneuvers. An MNA > 9 mm(2) was considered diagnostic of CTS. RESULTS:
      Measurement of MNA by US was > 9 mm(2) in 27% of the hands. A good association
      with pain (p < 0.0001), paresthesia (p < 0.0001), Tinel test (p < 0.0001) and
      Phalen test (p < 0.0001) was found. According to the clinical criteria for
      classification of CTS from American Academy of Neurology the MNA by US had 64.8%
      of sensibility and 77.0% of specificity in this sample. CONCLUSION: Measurement
      of MNA by US performs well and can be used as first option for the investigation
      of patients with CTS.

PMID- 25771162
TI  - Prevalence of Hepatitis E Virus in Populations of Wild Animals in Comparison with
      Animals Bred in Game Enclosures.
AB  - Hepatitis E virus (HEV) is now accepted as a zoonotic virus, and domestic pigs,
      wild boars and deer are recognised as natural reservoirs of the pathogen. In this
      study, 762 animals (wild boars, fallow deer, red deer, sika deer, roe deer and
      mouflons) originating from the wild and from game enclosures were tested for the
      presence of HEV RNA by qRT-PCR. HEV RNA was detected in wild boars (96/450), red
      deer (2/169), roe deer (1/30) and mouflons (5/39). The sequence relationship
      between HEV isolates from wild boars and domestic pigs or humans indicate a
      circulation of HEV in the Czech Republic.

PMID- 25771163
TI  - Two Japanese familial cases of punctate palmoplantar keratoderma caused by a
      novel AAGAB mutation, c.191_194delCAAA.

PMID- 25771164
TI  - Possible correlation of IgE autoantibody to BP180 with disease activity in
      bullous pemphigoid.

PMID- 25771165
TI  - Recent advances in atopic dermatitis and psoriasis: genetic background, barrier
      function, and therapeutic targets.
AB  - Atopic dermatitis (AD) and psoriasis are common inflammatory skin diseases.
      Although clinical pictures of these two diseases are quite different, they share
      some common pathological backgrounds such as barrier dysfunction and enhanced IL
      22 expression. To explain the clinical differences of the diseases, it has been
      proposed that Th2/Th22-polarized immune status together with an attenuated Th17
      axis may cause insufficient induction of antimicrobial peptides and more severe
      barrier dysfunction in AD. While skin barrier dysfunction is commonly seen in AD
      and psoriasis, a Th2-dominant cytokine milieu down-regulates immunity against
      infections, which are commonly seen in lesional skin of AD. In the era of
      biologics, increase in the understanding or new discoveries of molecules involved
      in the development of various diseases will instantly lead to a new therapeutic
      strategy. In this review, we give an overview of recent advances in AD and
      psoriasis, especially on genetic background, barrier function, and therapeutic
      targets. 

PMID- 25771166
TI  - Lymphatic flow is mostly preserved after sentinel lymph node biopsy in primary
      cutaneous malignant melanoma.
AB  - BACKGROUND: Knowledge of changes in lymphatic flow after sentinel lymph node
      biopsy (SLNB) is important for the development of strategies for postoperative
      adjuvant therapy in malignant melanoma. OBJECTIVES: 41 patients (22 males and 19
      females; average age: 67.0 +/- 24.0 years) with primary cutaneous malignant
      melanoma (PCMM) participated in the present study. The primary tumor sites were
      the upper extremities (9 patients), the lower extremities (20 patients), the
      trunk (11 patients) and the scalp (1 patient). The tumor thicknesses of the PCMM
      lesions were from 0.5mm to 9.0mm (average: 3.3 +/- 2.5mm). All the participants
      underwent wide local excision and SLNB. METHODS: We studied lymphatic flow before
      and after SLNB by near-infrared (NIR) imaging in all 41 cases. In addition, we
      performed NIR imaging of lymphatic flow after the lymph node dissection in one
      case with sentinel lymph node (SLN) metastasis. RESULTS: Almost no changes in
      lymphatic flow were seen in 38 of the 41 patients (92.7%) after SLNB. Only in 3
      patients (7.3%), one with SLN metastasis and the other two without SLN
      metastasis, was apparent alteration in the lymphatic flow observed after SLNB. Of
      the 16 patients without SLN metastasis, only 3 patients showed recurrence of the
      tumors. Interestingly, 1 of the 2 patients without SLN metastasis but with
      lymphatic flow alteration had recurrence (regional lymph node metastasis) of the
      melanoma, whereas only 2 of the 14 patients without SLN metastasis or lymphatic
      flow alteration had recurrence, 1 with regional lymph node metastasis and the
      other with distant lymph node metastasis. In 1 case, we re-examined the lymphatic
      flow after regional lymph node dissection and the lymphatic flow was found to be
      dramatically changed. CONCLUSION: We clearly demonstrated that SLNB has only a
      minimal effect on lymphatic flow. The present results suggest that SLNB does not
      increase the risk of local recurrence/in-transit metastasis and may support the
      efficacy of post-SLNB local adjuvant injection to prevent local recurrence and in
      transit metastasis.

PMID- 25771167
TI  - The BDNF Val66Met variant affects gene expression through miR-146b.
AB  - Variation in gene expression is an important mechanism underlying susceptibility
      to complex disease and traits. Single nucleotide polymorphisms (SNPs) account for
      a substantial portion of the total detected genetic variation in gene expression
      but how exactly variants acting in trans modulate gene expression and disease
      susceptibility remains largely unknown. The BDNF Val66Met SNP has been associated
      with a number of psychiatric disorders such as depression, anxiety disorders,
      schizophrenia and related traits. Using global microRNA expression profiling in
      hippocampus of humanized BDNF Val66Met knock-in mice we showed that this variant
      results in dysregulation of at least one microRNA, which in turn affects
      downstream target genes. Specifically, we show that reduced levels of miR-146b
      (mir146b), lead to increased Per1 and Npas4 mRNA levels and increased Irak1
      protein levels in vitro and are associated with similar changes in the
      hippocampus of hBDNF(Met/Met) mice. Our findings highlight trans effects of
      common variants on microRNA-mediated gene expression as an integral part of the
      genetic architecture of complex disorders and traits. 

PMID- 25771168
TI  - Differential roles of Abeta processing in hypoxia-induced axonal damage.
AB  - Axonopathy is a common and early phase in neurodegenerative and traumatic CNS
      diseases. Recent work suggests that amyloid beta (Abeta) produced from amyloid
      precursor protein (APP) may be a critical downstream mediator of CNS axonopathy
      in CNS diseases, particularly those associated with hypoxia. We critically tested
      this hypothesis in an adult retinal explant system that preserves the three
      dimensional organization of the retina while permitting direct imaging of two
      cardinal features of early-stage axonopathy: axonal structural integrity and
      axonal transport capacity. Using this system, we found via pharmacological
      inhibition and genetic deletion of APP that production of Abeta is a necessary
      step in structural compromise of retinal ganglion cell (RGC) axons induced by the
      disease-relevant stressor hypoxia. However, identical blockade of Abeta
      production was not sufficient to protect axons from associated hypoxia-induced
      reduction in axonal transport. Thus, Abeta mediates distinct facets of hypoxia
      induced axonopathy and may represent a functionally selective pharmacological
      target for therapies directed against early-stage axonopathy in CNS diseases. 

PMID- 25771169
TI  - Interrogating the aged striatum: robust survival of grafted dopamine neurons in
      aging rats produces inferior behavioral recovery and evidence of impaired
      integration.
AB  - Advanced age is the primary risk factor for Parkinson's disease (PD). In PD
      patients and rodent models of PD, advanced age is associated with inferior
      symptomatic benefit following intrastriatal grafting of embryonic dopamine (DA)
      neurons, a pattern believed to result from decreased survival and reinnervation
      provided by grafted neurons in the aged host. To help understand the capacity of
      the aged, parkinsonian striatum to be remodeled with new DA terminals, we used a
      grafting model and examined whether increasing the number of grafted DA neurons
      in aged rats would translate to enhanced behavioral recovery. Young (3months),
      middle-aged (15months), and aged (22months) parkinsonian rats were grafted with
      proportionately increasing numbers of embryonic ventral mesencephalic (VM) cells
      to evaluate whether the limitations of the graft environment in subjects of
      advancing age can be offset by increased numbers of transplanted neurons. Despite
      robust survival of grafted neurons in aged rats, reinnervation of striatal
      neurons remained inferior and amelioration of levodopa-induced dyskinesias (LID)
      was delayed or absent. This study demonstrates that: 1) counter to previous
      evidence, under certain conditions the aged striatum can support robust survival
      of grafted DA neurons; and 2) unknown factors associated with the aged striatum
      result in inferior integration of graft and host, and continue to present
      obstacles to full therapeutic efficacy of DA cell-based therapy in this model of
      aging. 

PMID- 25771170
TI  - Redox regulation of autophagy in healthy brain and neurodegeneration.
AB  - Autophagy and redox biochemistry are two major sub disciplines of cell biology
      which are both coming to be appreciated for their paramount importance in the
      etiology of neurodegenerative diseases including Alzheimer's disease (AD). Thus
      far, however, there has been relatively little exploration of the interface
      between autophagy and redox biology. Autophagy normally recycles macro-molecular
      aggregates produced through oxidative-stress mediated pathways, and also may
      reduce the mitochondrial production of reactive oxygen species through recycling
      of old and damaged mitochondria. Conversely, dysfunction in autophagy initiation,
      progression or clearance is evidenced to increase aggregation-prone proteins in
      neural and extraneural tissues. Redox mechanisms of autophagy regulation have
      been documented at the level of cross-talk between the Nrf2/Keap1 oxidant and
      electrophilic defense pathway and p62/sequestosome-1 (SQSTM1)-associated
      autophagy, at least in extraneural tissue; but other mechanisms of redox
      autophagy regulation doubtless remain to be discovered and the relevance of such
      processes to maintenance of neural homeostasis remains to be determined. This
      review summarizes current knowledge regarding the relationship of redox
      signaling, autophagy control, and oxidative stress as these phenomena relate to
      neurodegenerative disease. AD is specifically addressed as an example of the
      theme and as a promising indication for new therapies that act through engagement
      of autophagy pathways. To exemplify one such novel therapeutic entity, data is
      presented that the antioxidant and neurotrophic agent lanthionine ketimine-ethyl
      ester (LKE) affects autophagy pathway proteins including beclin-1 in the 3xTg-AD
      model of Alzheimer's disease where the compound has been shown to reduce
      pathological features and cognitive dysfunction. 

PMID- 25771171
TI  - Iron misregulation and neurodegenerative disease in mouse models that lack iron
      regulatory proteins.
AB  - Iron regulatory proteins 1 and 2 (IRP1 and IRP2) are two cytosolic proteins that
      maintain cellular iron homeostasis by binding to RNA stem loops known as iron
      responsive elements (IREs) that are found in the untranslated regions of target
      mRNAs that encode proteins involved in iron metabolism. IRPs modify the
      expression of iron metabolism genes, and global and tissue-specific knockout mice
      have been made to evaluate the physiological significance of these iron
      regulatory proteins (Irps). Here, we will discuss the results of the studies that
      have been performed with mice engineered to lack the expression of one or both
      Irps and made in different strains using different methodologies. Both Irp1 and
      Irp2 knockout mice are viable, but the double knockout (Irp1(-/-)Irp2(-/-)) mice
      die before birth, indicating that these Irps play a crucial role in maintaining
      iron homeostasis. Irp1(-/-) mice develop polycythemia and pulmonary hypertension,
      and when these mice are challenged with a low iron diet, they die early of
      abdominal hemorrhages, suggesting that Irp1 plays an essential role in
      erythropoiesis and in the pulmonary and cardiovascular systems. Irp2(-/-) mice
      develop microcytic anemia, erythropoietic protoporphyria and a progressive
      neurological disorder, indicating that Irp2 has important functions in the
      nervous system and erythropoietic homeostasis. Several excellent review articles
      have recently been published on Irp knockout mice that mainly focus on Irp1(-/-)
      mice (referenced in the introduction). In this review, we will briefly describe
      the phenotypes and physiological implications of Irp1(-/-) mice and discuss the
      phenotypes observed for Irp2(-/-) mice in detail with a particular emphasis on
      the neurological problems of these mice. 

PMID- 25771172
TI  - Up-regulation of interleukin-22 mediates liver fibrosis via activating hepatic
      stellate cells in patients with hepatitis C.
AB  - Interleukin-22 (IL-22) is known to play a critical role in liver immunity.
      However, the role of IL-22 in HCV-associated liver fibrosis is poorly understood.
      In this study, patients with HCV infection disclosed significant increases in
      peripheral numbers of IL-22-producing cells as well as in IL-22 plasma levels. In
      the liver, the increased intrahepatic IL-22(+) cells were positively correlated
      with fibrotic staging scores and clinical progression from CHC to cirrhosis.
      Moreover, the majority of IL-22(+) cells were located in fibrotic areas in the
      liver of patients with cirrhosis and co-localized with alpha-smooth muscle actin
      (alpha-SMA) positive hepatic stellate cells (HSCs). In vitro, administration of
      IL-22 was accompanied with inhibited LX-2 cell apoptosis, promoted LX-2 cell
      proliferation, increased expression of alpha-SMA, and up-regulated collagen
      production by LX-2 cells. Collectively, our data provide evidence that IL-22 may
      contribute to the fibrogenesis of HCV-associated liver fibrosis by activating
      HSCs.

PMID- 25771173
TI  - Mechanisms of action for arsenic in cardiovascular toxicity and implications for
      risk assessment.
AB  - The possibility of an association between inorganic arsenic (iAs) exposure and
      cardiovascular outcomes has received increasing attention in the literature over
      the past decade. The United States Environmental Protection Agency (US EPA) is
      currently revising its Integrated Risk Assessment System (IRIS) review of iAs,
      and one of the non-cancer endpoints of interest is cardiovascular disease (CVD).
      Despite the increased interest in this area, substantial gaps remain in the
      available information, particularly regarding the mechanism of action (MOA) by
      which iAs could cause or exacerbate CVD. Few studies specifically address the
      plausibility of an association between iAs and CVD at the low exposure levels
      which are typical in the United States (i.e., below 100 MUg As/L in drinking
      water). We have conducted a review and evaluation of the animal, mechanistic, and
      human data relevant to the potential MOAs of iAs and CVD. Specifically, we
      evaluated the most common proposed MOAs, which include disturbance of endothelial
      function and hepatic dysfunction. Our analysis of the available evidence
      indicates that there is not a well-established MOA for iAs in the development or
      progression of CVD. Few human studies of the potential MOAs have addressed
      plausibility at low doses and the applicability of extrapolation from animal
      studies to humans is questionable. However, the available evidence indicates that
      regardless of the specific MOA, the effects of iAs on physiological processes at
      the cellular level appear to operate via a threshold mechanism. This finding is
      consistent with the lack of association of CVD with iAs exposure in humans at
      levels below 100 MUg/L, particularly when considering important exposure and risk
      modifiers such as nutrition and genetics. Based on this analysis, we conclude
      that there are no data supporting a linear dose-response relationship between iAs
      and CVD, indicating this relationship has a threshold.

PMID- 25771174
TI  - [Pharmacovigilance center --internal medicine interactions: A useful diagnostic
      tool].
AB  - PURPOSE: Patients hospitalized in internal medicine often have unexplained
      clinical symptoms for which a drug origin can be considered. The prevalence of
      patients hospitalized for iatrogenic is estimated between 4-22%. We wanted to
      evaluate the diagnostic value of the regional center of pharmacovigilance to
      identify or confirm an iatrogenic disease in the department of internal medicine
      of Lille and characterize factors associated with drug-related side effect.
      METHODS: This is a single-center prospective diagnostic study. We included all
      subsequent requests from the department of internal medicine with the Nord-Pas-de
      Calais regional pharmacovigilance center between 2010 and 2012. The opinion of
      the regional pharmacovigilance centre was held on the record of the adverse drug
      reaction in the national pharmacovigilance database and analyzed according to the
      conclusion of iatrogenic used by clinicians in internal medicine (reference
      diagnosis) with a follow-up to June 2013. The variables relating to the patient,
      medication and adverse events were analyzed by binary logistic regression.
      RESULTS: We analyzed 160 contacts: 118 concordant cases, 38 false-positives (drug
      related side effect retained by the regional pharmacovigilance center only), 4
      false negatives. Registration in the national pharmacovigilance database had a
      sensitivity of 96% (95% CI [0.92 to 0.99]), a specificity of 46% (95% CI [0.38 to
      0.53]), a value positive predictive of 69% (95% CI [0.62 to 0.76]), a negative
      predictive value of 89% (95% CI [0.84 to 0.94]) and a negative likelihood ratio
      of 0.1. False-positive had chronological and semiological accountabilities
      questionable (adjusted RR=2.1, 95% CI [1.2 to 2.8]). CONCLUSION: In our study,
      the regional pharmacovigilance center confirms the clinician's suspicion of drug
      related side effects and helps to exclude drug-induced with a high negative
      predictive value.

PMID- 25771175
TI  - [Lower limb pain of unusual cause].

PMID- 25771176
TI  - Postural stability under globus pallidus internus stimulation for dystonia.
AB  - OBJECTIVE: Deep brain stimulation of the globus pallidus internus (GPi-DBS) is an
      efficient and safe treatment for medically refractory dystonia. However, recent
      studies reported gait problems, falls and bradykinesia in patients after the DBS
      procedure. The aim of this study was to quantify the effect of GPi-DBS on
      postural performance in patients with cranio-cervical dystonia. METHODS: Thirteen
      patients with focal/segmental dystonia and GPi-DBS participated in the study. We
      performed two postural tests (pull test and push and release test) in on- and off
      stimulation conditions and recorded the movements of the patients with inertial
      sensors. RESULTS: Under stimulation patients exhibited a higher number of steps
      (p=0.015), reduced first step length (p=0.011) and lower stepping velocity
      (p=0.001), compared to off stimulation. We observed a higher number of steps in
      the push and release test compared to the pull test (p=0.038). The interaction
      between stimulation condition and test type was significant (p=0.027).
      CONCLUSIONS: The velocity and amplitude of postural reactions are compromised by
      GPi-DBS in patients with cranio-cervical dystonia. SIGNIFICANCE: This information
      corresponds to patient's reports of falls and postural instability after GPi-DBS.
      Pre-operatively, patients should be informed about the possibility of the
      occurrence of such phenomena.

PMID- 25771177
TI  - Effects of the non-commensal Methylococcus capsulatus Bath on mammalian immune
      cells.
AB  - Dietary inclusions of a bacterial meal consisting mainly of the non-commensal,
      methanotrophic bacteria Methylococcus capsulatus Bath have been shown to
      ameliorate symptoms of intestinal inflammation in different animal models. In
      order to investigate the molecular mechanisms causing these effects, we have
      studied the influence of this strain on different immune cells central for the
      regulation of inflammatory responses. Effects were compared to those induced by
      the closely related strain M. capsulatus Texas and the well-described probiotic
      strain Escherichia coli Nissle 1917. M. capsulatus Bath induced macrophage
      polarization toward a pro-inflammatory phenotype, but not to the extent observed
      after exposure to E. coli Nissle 1917. Likewise, dose-dependent abilities to
      activate NF-kappaB transcription in U937 cells were observed, with E. coli Nissle
      1917 being most potent. High levels of CD141 on human primary monocyte-derived
      dendritic cells (moDCs) were only detected after exposure to E. coli Nissle 1917,
      which collectively indicate a superior capacity to induce Th1 cell responses for
      this strain. On the other hand, the M. capsulatus strains were more potent in
      increasing the expression of the maturation markers CD80, CD83 and CD86 than E.
      coli Nissle 1917. M. capsulatus Bath induced the highest levels of IL-6, IL-10
      and IL-12 secretion from dendritic cells, suggesting that this strain generally
      the post potent inducer of cytokine secretion. These results show that M.
      capsulatus Bath exhibit immunogenic properties in mammalian in vitro systems
      which diverge from that of E. coli Nissle 1917. This may provide clues to how M.
      capsulatus Bath influence the adaptive immune system in vivo. However, further in
      vivo experiments are required for a complete understanding of how this strain
      ameliorates intestinal inflammation in animal models.

PMID- 25771178
TI  - Disruption of TIM-4 in dendritic cell ameliorates hepatic warm IR injury through
      the induction of regulatory T cells.
AB  - Hepatic ischaemia reperfusion (IR) injury results from the infiltration of
      multiple immune cells especially dendritic cells (DC). T-cell immunoglobulin
      domain and mucin-domain 4 (TIM-4) is a type I cell-surface glycoprotein which is
      extensively expressed on antigen presenting cells (APC) like DC and macrophages.
      TIM-4 has been demonstrated to be implicated in mucosal allergy, skin allograft
      rejection and tumour-immune tolerance. However, the role of TIM-4 expressed on DC
      in hepatic IR injury remains largely unknown. In the present study, we aimed to
      investigate whether and how DC expressed TIM-4 was involved in hepatic IR injury.
      With segmental hepatic warm ischaemia mice models, we demonstrated that promoted
      DC infiltration and increased TIM-4 expression were induced by hepatic IR.
      Blockade of TIM-4 by anti-TIM-4 mAb (0.35mg/mouse) markedly ameliorated hepatic
      injury and reduced inflammatory cytokine secretion. Furthermore, in a DC:CD4+ T
      cell co-culture system, blockade of TIM-4 on DC significantly inhibited T helper
      2 cell differentiation and facilitated induced CD4+ CD25+ Foxp3+ T regulatory
      cell (iTreg) expansion. Interleukin-4 (IL-4)/signal transducer and activator of
      transcription 6 (Stat 6) signalling was shown to be impeded by TIM-4 blockade and
      involved in iTreg generation. Additionally, adoptive transfer of iTreg produced
      by TIM-4 blockade into hepatic IR mice models remarkably attenuated liver injury.
      We conclude that TIM-4 on DC play a critical role in hepatic IR injury and may be
      an efficient target for the prevention of liver or other organ IR injury.

PMID- 25771179
TI  - The Src tyrosine kinase Lck binds to CD2, CD4-1, and CD4-2 T cell co-receptors in
      channel catfish, Ictalurus punctatus.
AB  - The binding of the lymphocyte specific protein tyrosine kinase (Lck) to T cell co
      receptors is required for T cell development and activation. In mammals, Lck
      initiates signal transduction by binding to CD4 and CD8 co-receptors and
      phosphorylating ITAMs in the cytoplasmic tail of the CD3 molecules and the zeta
      chains. In addition, Lck can also bind to the adhesion molecule CD2 and trigger T
      cell activation. In this study, Lck and CD2 homologs were identified and
      characterized in channel catfish, Ictalurus punctatus. Lck and CD2 mRNAs were
      specifically expressed by clonal T cell lines, including both CD4(+) and CD4(
      )CD8(-) CTL lines, and in mixed lymphocyte cultures (MLC). Western blot analyses
      using anti-trout Lck and anti-human p-Lck antibodies demonstrated that Lck
      protein is expressed in catfish clonal CTL and is phosphorylated at a conserved
      tyrosine residue. Because of the lack of CD8(+) CTL lines as well as the absence
      of CD8 message in MLC, we performed magnetic bead binding assays to correlate
      CD2, CD4, and CD8 co-receptor expression with Lck binding ability. Recombinant
      Lck reproducibly bound to CD2, CD4-1, and CD4-2, but not to CD8alpha or CD8beta.
      These data provide one possible explanation for the apparent low numbers of
      CD8(+) CTL and the presence of CD4(+) and CD4(-)CD8(-)CD2(+) CTL in catfish.

PMID- 25771180
TI  - Characterizing the inhibitory action of zinc oxide nanoparticles on allergic-type
      mast cell activation.
AB  - The development of nanoparticles (NPs) for commercial products is undergoing a
      dramatic expansion. Many sunscreens and cosmetics now use zinc oxide (ZnO) or
      titania (TiO2) NPs, which are effective ultraviolet (UV) filters. Zinc oxide
      topical creams are also used in mild anti-inflammatory treatments. In this study
      we evaluated the effect of size and dispersion state of ZnO and TiO2 NPs,
      compared to "bulk" ZnO, on mast cell degranulation and viability. ZnO and TiO2
      NPs were characterized using dynamic light scattering and disc centrifugation.
      Rat basophilic leukaemia (RBL-2H3) cells and primary mouse bone marrow-derived
      mast cells (BMMCs) were exposed to ZnO and TiO2 NPs of different sizes (25-200
      nm) and surface coatings at concentrations from 1 to 200 MUg/mL. The effect of
      NPs on immunoglobulin E (IgE)-dependent mast cell degranulation was assessed by
      measuring release of both beta-hexosaminidase and histamine via colorimetric and
      ELISA assays. The intracellular level of Zn(2+) and Ca(2+) ions were measured
      using zinquin ethyl ester and Fluo-4 AM fluorescence probes, respectively.
      Cellular viability was determined using the soluble tetrazolium-based MTS
      colorimetric assay. Exposure of RBL-2H3 and primary mouse BMMC to ZnO NPs
      markedly inhibited both histamine and beta-hexosaminidase release. This effect
      was both particle size and dispersion dependent. In contrast, TiO2 NPs did not
      inhibit the allergic response. These effects were independent of cytotoxicity,
      which was observed only at high concentrations of ZnO NPs, and was not observed
      for TiO2 NPs. The inhibitory effects of ZnO NPs on mast cells were inversely
      proportional to particle size and dispersion status, and thus these NPs may have
      greater potential than "bulk" zinc in the inhibition of allergic responses.

PMID- 25771181
TI  - Mycobacterium tuberculosis Rv2185c contributes to nuclear factor-kappaB
      activation.
AB  - Tuberculosis caused by Mycobacterium tuberculosis has a detrimental impact on
      public health worldwide, especially in developing countries. The nuclear factor
      kappaB (NF-kappaB) signaling pathway is reportedly involved in the innate immune
      response against M. tuberculosis infections. We screened the secreted proteins,
      membrane proteins, and lipoproteins of the M. tuberculosis H37Rv strain using
      luciferase activity assays. The Rv2185c protein exhibited the potential to
      activate NF-kappaB in HeLa and A549 cells. Overexpression of Rv2185c-induced
      IkappaBalpha degradation and nuclear translocation of NF-kappaB; it also induced
      NF-kappaB-dependent inflammatory factors, including interleukin (IL)-6, IL-8, IL
      1beta and tumor necrosis factor (TNF)-alpha. The intact binding site for the NF
      kappaB element is required for the activation of Rv2185c-induced IL-6 and IL-8
      gene expression. NF-kappaB activation and NF-kappaB-regulated genes encoding TNF
      alpha and TNF-related apoptosis-inducing ligand have also been shown to be
      involved in Rv2185c-induced apoptosis.

PMID- 25771182
TI  - The relationship between quality of life and foot function in children with
      flexible flatfeet.
AB  - Flat feet in children are common, and at times symptomatic, but the relationship
      between function and symptoms or impairment is still unclear. We undertook a
      prospective, observational study comparing children with paediatric flexible flat
      foot (PFF) and children with neutral feet (NF) using three dimensional gait
      analysis (3DGA). It was hypothesised that children with PFF would demonstrate
      differences in both spatio-temporal parameters of gait and foot and ankle
      kinematics compared to the NF group and that these differences would correlate
      with impaired quality of life (QoL). The kinematic differences were expected to
      be most marked in hindfoot coronal plane motion and forefoot sagittal and
      transverse plane motion. Eighty-three children between the ages of 8 and 15 were
      recruited in this study: Forty-two were classified as having PFF and forty-one as
      NF. Each child underwent 3DGA and completed the Oxford Ankle Foot Questionnaire
      for Children (OxAFQ_C). Reduced OxAFQ_C physical domain scores in the PFF
      children were associated with slower walking speed (p=0.014) and reduced
      normalised stride length (p=0.008). PFF children also demonstrated significantly
      increased hindfoot eversion and forefoot supination during gait. Significant
      differences between groups were not observed for other foot and ankle joint
      motions. Increased maximum hindfoot eversion and increased forefoot supination
      correlated strongly with lower QoL scores in PFF children. These data further our
      understanding of the functional characteristics that lead to impaired QoL in PFF
      children. These findings will help guide the surveillance and management of
      children with this ubiquitous condition. 

PMID- 25771183
TI  - Transport and quality control of MHC class I molecules in the early secretory
      pathway.
AB  - Folding and peptide binding of major histocompatibility complex (MHC) class I
      molecules have been thoroughly researched, but the mechanistic connection between
      these biochemical events and the progress of class I through the early secretory
      pathway is much less well understood. This review focuses on the question how the
      partially assembled forms of class I (which lack high-affinity peptide and/or the
      light chain beta-2 microglobulin) are retained inside the cell. Such
      investigations offer researchers exciting chances to understand the connections
      between class I structure, conformational dynamics, peptide binding kinetics and
      thermodynamics, intracellular transport, and antigen presentation. 

PMID- 25771185
TI  - Collective genius.

PMID- 25771184
TI  - New insights into type I interferon and the immunopathogenesis of persistent
      viral infections.
AB  - Most viruses generate potent T cell responses that rapidly control infection.
      However, certain viruses can subvert the immune response to establish persistent
      infections. The inability to clear virus induces an immunosuppressive program
      leading to the sustained expression of many immunoregulatory molecules that down
      regulate T cell responses. Further, viral persistence is associated with multiple
      immune dysfunctions including lymphoid disorganization, defective antigen
      presentation, aberrant B cell responses and hypergammaglobulinemia. Although best
      known for its antiviral activity, recent data has highlighted the role of type I
      IFN (IFN-I) signaling as a central mediator of immunosuppression during viral
      persistence. It is also becoming increasingly apparent that many of the immune
      dysfunctions during persistent virus infection can be attributed directly or
      indirectly to the effects of chronic IFN-I signaling. This review explores the
      increasingly complex role of IFN-I in the regulation of immunity against
      persistently replicating virus infections and examines current and potential uses
      of IFN-I and blockade of IFN-I signaling to dampen chronic inflammation and
      activation in the clinic. 

PMID- 25771186
TI  - Creativity in policy.

PMID- 25771187
TI  - Career legacy map.

PMID- 25771188
TI  - Enabling nurses to lead change: the orientation experiences of nurses to boards.
AB  - OBJECTIVES: Nurses need to be full partners in shaping health care and health
      care policy. One way to do this is to be present and active on boards at all
      levels. The purpose of this study is to examine the orientation experiences of
      nurses to boards and their preparation to influence health care and health care
      policy. METHODS: A Web-based survey about the efficacy of board orientation was
      sent to members of three local boards made up exclusively of nurses. RESULTS:
      Liabilities and fiduciary duties were least likely to be addressed in board
      orientation for nurses. Board members requested more training in finance and a
      more formal/structured orientation process. CONCLUSIONS: Standardizing
      orientation elements for nurses serving on boards would best prepare them to
      serve on interprofessional hospital boards and work in the health policy arena.
      The orientation experience on local- and state-level nursing boards is
      fundamental to nurses beginning board service.

PMID- 25771190
TI  - A revised Self- and Family Management Framework.
AB  - BACKGROUND: Research on self- and family management of chronic conditions has
      advanced over the past 6 years, but the use of simple frameworks has hampered the
      understanding of the complexities involved. PURPOSE: We sought to update our
      previously published model with new empirical, synthetic, and theoretical work.
      METHODS: We used synthesis of previous studies to update the framework.
      DISCUSSION: We propose a revised framework that clarifies facilitators and
      barriers, processes, proximal outcomes, and distal outcomes of self- and family
      management and their relationships. CONCLUSIONS: We offer the revised framework
      as a model that can be used in studies aimed at advancing self- and family
      management science. The use of the framework to guide studies would allow for the
      design of studies that can address more clearly how self-management interventions
      work and under what conditions.

PMID- 25771189
TI  - Exploring leadership roles, goals, and barriers among Kansas registered nurses: a
      descriptive cross-sectional study.
AB  - OBJECTIVES: The Institute of Medicine's Future of Nursing report advocates for
      full nurse leader representation across multiple settings to address current
      challenges in our health care system. The purpose of this study was to examine
      nursing leadership development needs among Kansas registered nurses (RNs).
      METHODS: Data were collected through an online survey and analyzed using
      quantitative and qualitative methods. RESULTS: Nearly 1,000 Kansas RNs
      participated. Most reported holding one or more leadership positions. Prevalent
      leadership goals were health care organization volunteer administrative roles.
      The most frequently identified barrier to developing leadership roles was time
      constraints. Many wanted to develop skills to serve on a board, 20% were
      interested in personal leadership development, and 19% in policy development.
      CONCLUSIONS: Based on the findings, the Kansas Action Coalition leadership team
      is developing programs to address the leadership needs of Kansas RNs. By building
      capacity in advanced leadership roles, RNs will be better prepared serve as full
      partners and lead efforts to promote the health of Kansans.

PMID- 25771191
TI  - Establishing good collaborative research practices in the responsible conduct of
      research in nursing science.
AB  - BACKGROUND: Team science is advocated to speed the pace of scientific discovery,
      yet the goals of collaborative practice in nursing science and the
      responsibilities of nurse stakeholders are sparse and inconclusive. The purpose
      of this study was to examine nurse scientists' views on collaborative research as
      part of a larger study on standards of scientific conduct. METHODS: Web-based
      descriptive survey of nurse scientists randomly selected from 50 doctoral
      graduate programs in the United States. RESULTS: Nearly forty percent of nurse
      respondents were not able to identify good collaborative practices for the
      discipline; more than three quarters did not know of any published guidelines
      available to them. Successful research collaborations were challenged by
      different expectations of authorship and data ownership, lack of timeliness and
      communication, poorly defined roles and responsibilities, language barriers, and
      when they involve junior and senior faculty working together on a project.
      CONCLUSION: Individual and organizational standards, practices, and policies for
      collaborative research needs clarification within the discipline.

PMID- 25771192
TI  - Implementing common data elements across studies to advance research.
AB  - Challenges arise in building the knowledge needed for evidence-based practice
      partially because obtaining clinical research data is expensive and complicated,
      and many studies have small sample sizes. Combining data from several studies may
      have the advantage of increasing the impact of the findings or expanding the
      population to which findings may be generalized. The use of common data elements
      will allow this combining and, in turn, create big data, which is an important
      approach that may accelerate knowledge development. This article discusses the
      philosophy of using common data elements across research studies and illustrates
      their use by the processes in a developmental center grant funded by the National
      Institutes of Health. The researchers identified a set of data elements and used
      them across several pilot studies. Issues that need to be considered in the
      adoption and implementation of common data elements across pilot studies include
      theoretical framework, purpose of the common measures, respondent burden,
      teamwork, managing large data sets, grant writing, and unintended consequences.
      We describe these challenges and solutions that can be implemented to manage
      them. 

PMID- 25771193
TI  - A new model for postdoctoral training: the Nursing Postdoctoral Program in Cancer
      and Health Disparities.
AB  - The University of Massachusetts Boston and Dana-Farber/Harvard Cancer Center
      joined forces in 2009 to create a Postdoctoral Nursing Research Fellowship in
      Cancer and Health Disparities. In combining the resources of a large university
      and a research-intensive service institution, the postdoctoral program provides a
      new model for preparing nurse scientists to conduct independent research that
      advances nursing knowledge and interdisciplinary understanding of complex health
      issues. The multifaceted program consists of educational programming, research
      training, and career planning components. Additionally, each fellow is assigned a
      nurse scientist mentor and interdisciplinary co-mentor. The mentors support the
      fellows with scholarly activities and research training and help the fellows
      craft individualized career plans, including proposals for postfellowship career
      development research. In this article, the postdoctoral program leaders describe
      the program structure, strategies used to recruit minority and nonminority
      candidates, and data describing program outcomes and share lessons learned and
      recommendations for organizations that may be interested in establishing similar
      postdoctoral fellowships at their institutions. 

PMID- 25771194
TI  - The Colorado Collaborative for Nursing Research: nurses shaping nursing's future.
AB  - Nurses in the present health care environment have been reduced too often to
      being providers of safe, competent care rather than quality care. In response,
      the Institute of Medicine has recommended that nurses become more involved in
      making changes to the health care system and use data more effectively. If
      nursing intends to follow these recommendations, the profession needs (a) fresh
      perspectives to assist in making health care system changes, (b) partnerships
      between nurse scientists and nurse clinicians to generate and implement data, and
      (c) capture of the proper value of nursing as distinct from other elements of
      health care delivery. The Colorado Collaborative for Nursing Research is an
      effort to meet the recommendations of the Institute of Medicine. The Colorado
      Collaborative for Nursing Research has a three-arm structure: a research forum
      where nurse academicians and nurse clinicians can launch collaborative projects;
      a research support services arm from which nurse collaborators can obtain help
      with modeling, statistics, writing, and funding; and a data extraction/data
      sharing mechanism to inform the decision making of nurse leaders. 

PMID- 25771195
TI  - Doctor of nursing practice by 2015: an examination of nursing schools' decisions
      to offer a doctor of nursing practice degree.
AB  - OBJECTIVES: The American Association of Colleges of Nursing recommends that
      nursing schools transition their advanced practice registered nurse (APRN)
      programs to doctor of nursing practice (DNP) programs by 2015. However, most
      schools have not yet made this full transition. The purpose of this study was to
      understand schools' decisions regarding the full transition to the DNP. METHODS:
      Key informant interviews and an online survey of nursing school deans and program
      directors were performed. DISCUSSION: The vast majority of schools value the DNP
      in preparing APRNs for the future of the health care system. However, other
      important factors influence many schools to fully transition or not to the
      postbaccalaureate DNP, including perceived student and employer demand, issues
      concerning accreditation and certification, and resource constraints. CONCLUSION:
      Multiple pathways to becoming an APRN are likely to remain until various factors
      (e.g., student and employer demand, certification and accreditation issues, and
      resource constraints) yield a more favorable environment for a full transition to
      the DNP.

PMID- 25771196
TI  - The Performance of the Date-Randomization Test in Phylogenetic Analyses of Time
      Structured Virus Data.
AB  - Rates and timescales of viral evolution can be estimated using phylogenetic
      analyses of time-structured molecular sequences. This involves the use of
      molecular-clock methods, calibrated by the sampling times of the viral sequences.
      However, the spread of these sampling times is not always sufficient to allow the
      substitution rate to be estimated accurately. We conducted Bayesian phylogenetic
      analyses of simulated virus data to evaluate the performance of the date
      randomization test, which is sometimes used to investigate whether time
      structured data sets have temporal signal. An estimate of the substitution rate
      passes this test if its mean does not fall within the 95% credible intervals of
      rate estimates obtained using replicate data sets in which the sampling times
      have been randomized. We find that the test sometimes fails to detect rate
      estimates from data with no temporal signal. This error can be minimized by using
      a more conservative criterion, whereby the 95% credible interval of the estimate
      with correct sampling times should not overlap with those obtained with
      randomized sampling times. We also investigated the behavior of the test when the
      sampling times are not uniformly distributed throughout the tree, which sometimes
      occurs in empirical data sets. The test performs poorly in these circumstances,
      such that a modification to the randomization scheme is needed. Finally, we
      illustrate the behavior of the test in analyses of nucleotide sequences of cereal
      yellow dwarf virus. Our results validate the use of the date-randomization test
      and allow us to propose guidelines for interpretation of its results. 

PMID- 25771197
TI  - Centromeres Off the Hook: Massive Changes in Centromere Size and Structure
      Following Duplication of CenH3 Gene in Fabeae Species.
AB  - In most eukaryotes, centromere is determined by the presence of the centromere
      specific histone variant CenH3. Two types of chromosome morphology are generally
      recognized with respect to centromere organization. Monocentric chromosomes
      possess a single CenH3-containing domain in primary constriction, whereas
      holocentric chromosomes lack the primary constriction and display dispersed
      distribution of CenH3. Recently, metapolycentric chromosomes have been reported
      in Pisum sativum, representing an intermediate type of centromere organization
      characterized by multiple CenH3-containing domains distributed across large parts
      of chromosomes that still form a single constriction. In this work, we show that
      this type of centromere is also found in other Pisum and closely related Lathyrus
      species, whereas Vicia and Lens genera, which belong to the same legume tribe
      Fabeae, possess only monocentric chromosomes. We observed extensive variability
      in the size of primary constriction and the arrangement of CenH3 domains both
      between and within individual Pisum and Lathyrus species, with no obvious
      correlation to genome or chromosome size. Search for CenH3 gene sequences
      revealed two paralogous variants, CenH3-1 and CenH3-2, which originated from a
      duplication event in the common ancestor of Fabeae species. The CenH3-1 gene was
      subsequently lost or silenced in the lineage leading to Vicia and Lens, whereas
      both genes are retained in Pisum and Lathyrus. Both of these genes appear to have
      evolved under purifying selection and produce functional CenH3 proteins which are
      fully colocalized. The findings described here provide the first evidence for a
      highly dynamic centromere structure within a group of closely related species,
      challenging previous concepts of centromere evolution. 

PMID- 25771199
TI  - Contribution of membrane trafficking perturbation to retinal toxicity.
AB  - The retina is a highly structured tissue that is formed by layers containing 7
      different cell types. The photoreceptor cell is a specialized type of neuron in
      the retina that is capable of absorbing and converting light into
      electrophysiological signals. There is a constant renewal process for
      photoreceptors consisting of intermittent shedding of the distal tips of the
      photosensitive outer segment and subsequent phagocytosis (uptake, degradation and
      recycling) by retinal pigmented epithelial (RPE) cells. This rebuilding process
      is essential for vision and the survival of photoreceptors and RPE cells. Drugs
      with a basic moiety have the potential to accumulate in the lysosome and impair
      its functions including the phagocytosis process, which could hinder clearance of
      outer segments and ultimately induce retinopathy. To determine the prevalence of
      this cellular mechanism in retinal toxicity, a collection of proprietary
      compounds associated with retinal toxicity were subjected to a battery of in
      vitro tests using the human adult retinal pigmented epithelium cell line, ARPE
      19. The tests included a phagocytosis assay, and lysosomal and autophagosomal
      staining. The compounds that induced retinopathy clustered in the basic and
      lipophilic region, which drives lysosomal sequestration. This accumulation
      coincided with phagocytosis inhibition and an increase in autophagosome staining,
      suggesting a blockage of the membrane trafficking process. A correlation between
      the physicochemical properties and in vitro lysosomal pathway effects was
      established. These data reveal the importance of physicochemical properties of
      compounds and lysosome accumulation as a potential mechanism for drug-induced
      retinopathy and demonstrate the usefulness of in vitro screening in predicting
      this liability.

PMID- 25771198
TI  - Why Selection Might Be Stronger When Populations Are Small: Intron Size and
      Density Predict within and between-Species Usage of Exonic Splice Associated cis
      Motifs.
AB  - The nearly neutral theory predicts that small effective population size provides
      the conditions for weakened selection. This is postulated to explain why our
      genome is more "bloated" than that of, for example, yeast, ours having large
      introns and large intergene spacer. If a bloated genome is also an error prone
      genome might it, however, be the case that selection for error-mitigating
      properties is stronger in our genome? We examine this notion using splicing as an
      exemplar, not least because large introns can predispose to noisy splicing. We
      thus ask whether, owing to genomic decay, selection for splice error-control
      mechanisms is stronger, not weaker, in species with large introns and small
      populations. In humans much information defining splice sites is in cis-exonic
      motifs, most notably exonic splice enhancers (ESEs). These act as splice-error
      control elements. Here then we ask whether within and between-species intron size
      is a predictor of the commonality of exonic cis-splicing motifs. We show that, as
      predicted, the proportion of synonymous sites that are ESE-associated and under
      selection in humans is weakly positively correlated with the size of the flanking
      intron. In a phylogenetically controlled framework, we observe, also as expected,
      that mean intron size is both predicted by Ne.MU and is a good predictor of cis
      motif usage across species, this usage coevolving with splice site definition.
      Unexpectedly, however, across taxa intron density is a better predictor of cis
      motif usage than intron size. We propose that selection for splice-related motifs
      is driven by a need to avoid decoy splice sites that will be more common in genes
      with many and large introns. That intron number and density predict ESE usage
      within human genes is consistent with this, as is the finding of intragenic
      heterogeneity in ESE density. As intronic content and splice site usage across
      species is also well predicted by Ne.MU, the result also suggests an unusual
      circumstance in which selection (for cis-modifiers of splicing) might be stronger
      when population sizes are smaller, as here splicing is noisier, resulting in a
      greater need to control error-prone splicing. 

PMID- 25771200
TI  - The Contribution of Transcriptomics to Biomarker Development in Systemic
      Vasculitis and SLE.
AB  - A small but increasing number of gene expression based biomarkers are becoming
      available for routine clinical use, principally in oncology and transplantation.
      These underscore the potential of gene expression arrays and RNA sequencing for
      biomarker development, but this potential has not yet been fully realized and
      most candidates do not progress beyond the initial report. The first part of this
      review examines the process of gene expression- based biomarker development,
      highlighting how systematic biases and confounding can significantly skew study
      outcomes. Adequate validation in an independent cohort remains the single best
      means of protecting against these concerns. The second part considers gene
      expression based biomarkers in Systemic Lupus Erythematosus (SLE) and systemic
      vasculitis. The type 1 interferon inducible gene signature remains by far the
      most studied in autoimmune rheumatic disease. While initially presented as an
      objective, blood-based biomarker of active SLE, subsequent research has shown
      that it is not specific to SLE and that its association with disease activity is
      considerably more nuanced than first thought. Nonetheless, it is currently under
      evaluation in ongoing trials of anti-interferon therapy. Other candidate markers
      of note include a prognostic CD8+ T-cell gene signature validated in SLE and ANCA
      associated vasculitis, and a disease activity biomarker for SLE derived from
      modules of tightly correlated genes. 

PMID- 25771202
TI  - The ancient city of Rome, its empire, and the spread of tuberculosis in Europe.
AB  - The formation of the Roman Empire constituted an unprecedented joining of
      Mediterranean and European lands and peoples, centering on the capital of Rome.
      During the late Roman Republic and early Roman Empire (ca. 200B.C.-ca. 200 A.D.)
      urbanization and population growth led to conditions favorable to the spread of
      tuberculosis throughout Italy and especially within Rome itself. Trade and
      military expansion would have acted as vehicles for the further extension of
      tuberculosis to the provinces via direct transmission from Italian-born Romans to
      the native populations. However, an alternative explanation may better explain
      the increase in the number of archeological cases of tuberculosis with the start
      of the Roman era. A literature review of Roman-era cases and their locations
      suggests that the development of an urban, Roman way of life resulted in
      significant increases in prevalence in regions where tuberculosis had previously
      been endemic only at a low level. 

PMID- 25771203
TI  - Evolutionary changes in the genome of Mycobacterium tuberculosis and the human
      genome from 9000 years BP until modern times.
AB  - The demonstration of Mycobacterium tuberculosis DNA in ancient skeletons gives
      researchers an insight into its evolution. Findings of the last two decades
      sketched the biological relationships between the various species of tubercle
      bacilli, the time scale involved, their possible origin and dispersal. This paper
      includes the available evidence and on-going research. In the submerged Eastern
      Mediterranean Neolithic village of Atlit Yam (9000 BP), a human lineage of M.
      tuberculosis, defined by the TbD1 deletion in its genome, was demonstrated. An
      infected infant at the site provides an example of active tuberculosis in a human
      with a naive immune system. Over 4000 years later tuberculosis was found in
      Jericho. Urbanization increases population density encouraging M.
      tuberculosis/human co-evolution. As susceptible humans die of tuberculosis,
      survivors develop genetic resistance to disease. Thus in 18th century Hungarian
      mummies from Vac, 65% were positive for tuberculosis yet a 95-year-old woman had
      clearly survived a childhood Ghon lesion. Whole genome studies are in progress,
      to detect changes over the millennia both in bacterial virulence and also host
      susceptibility/resistance genes that determine the NRAMP protein and Killer Cell
      Immunoglobulin-like Receptors (KIRs). This paper surveys present evidence and
      includes initial findings.

PMID- 25771201
TI  - CDH2 and CDH11 act as regulators of stem cell fate decisions.
AB  - Accumulating evidence suggests that the mechanical and biochemical signals
      originating from cell-cell adhesion are critical for stem cell lineage
      specification. In this review, we focus on the role of cadherin mediated
      signaling in development and stem cell differentiation, with emphasis on two well
      known cadherins, cadherin-2 (CDH2) (N-cadherin) and cadherin-11 (CDH11) (OB
      cadherin). We summarize the existing knowledge regarding the role of CDH2 and
      CDH11 during development and differentiation in vivo and in vitro. We also
      discuss engineering strategies to control stem cell fate decisions by fine-tuning
      the extent of cell-cell adhesion through surface chemistry and microtopology.
      These studies may be greatly facilitated by novel strategies that enable
      monitoring of stem cell specification in real time. We expect that better
      understanding of how intercellular adhesion signaling affects lineage
      specification may impact biomaterial and scaffold design to control stem cell
      fate decisions in three-dimensional context with potential implications for
      tissue engineering and regenerative medicine. 

PMID- 25771204
TI  - Morphological and biomolecular evidence for tuberculosis in 8th century AD
      skeletons from Belmegyer-Csomoki domb, Hungary.
AB  - Macromorphological analysis of skeletons, from 20 selected graves of the 8th
      century AD Belmegyer-Csomoki domb, revealed 19 cases of possible skeletal
      tuberculosis. Biomolecular analyses provided general support for such diagnoses,
      including the individual without pathology, but the data did not show coherent
      consistency over the range of biomarkers examined. Amplification of ancient DNA
      fragments found evidence for the Mycobacterium tuberculosis complex DNA only in
      five graves. In contrast, varying degrees of lipid biomarker presence were
      recorded in all except two of the skeletons, though most lipid components
      appeared to be somewhat degraded. Mycobacterial mycolic acid biomarkers were
      absent in five cases, but the weak, possibly degraded profiles for the remainder
      were smaller and inconclusive for either tuberculosis or leprosy. The most
      positive lipid biomarker evidence for tuberculosis was provided by mycolipenic
      acid, with 13 clear cases, supported by five distinct possible cases.
      Combinations of mycocerosic acids were present in all but three graves, but in
      one case a tuberculosis-leprosy co-infection was indicated. In two specimens with
      pathology, no lipid biomarker evidence was recorded, but one of these specimens
      provided M. tuberculosis complex DNA fragments.

PMID- 25771205
TI  - Determination of geniposide in adjuvant arthritis rat plasma by ultra-high
      performance liquid chromatography tandem mass spectrometry method and its
      application to oral bioavailability and plasma protein binding ability studies.
AB  - A specific, sensitive and high throughput ultra-high performance liquid
      chromatography-electrospray ionization tandem mass spectrometric method (UHPLC
      ESI-MS/MS) was established and validated to assay geniposide (GE), a promising
      anti-inflammatory drug, in adjuvant arthritis rat plasma: application to
      pharmacokinetic and oral bioavailability studies and plasma protein binding
      ability. Plasma samples were processed by de-proteinised with ice-cold methanol
      and separated on an ACQUITY UPLCTM HSS C18 column (100 mm * 2.1mm i.d., 1.8 MUm
      particle size) at a gradient flow rate of 0.2 mL/min using acetonitrile-0.1%
      formic acid in water as mobile phase, and the total run time was 9 min. Mass
      detection was performed in selected reaction monitoring (SRM) mode with negative
      electro-spray ionization includes the addition of paeoniflorin (Pae) as an
      internal standard (IS). The mass transition ion-pair was followed as m/z 387.4 ->
      122.4 for GE and m/z 479.4 -> 449.0 for IS. The calibration curves were linear
      over the concentration range of 2-50,000 ng/mL with lower limit of quantification
      of 2 ng/mL. The intra-day and inter-day precisions (RSD, %) of the assay were
      less than 8.4%, and the accuracy was within +/- 6.4% in terms of relative error
      (RE). Extraction recovery, matrix effect and stability were satisfactory in
      adjuvant arthritis rat plasma. The UHPLC-ESI-MS/MS method was successfully
      applied to a pharmacokinetic study of GE after oral administration of depurated
      GE at 33, 66, 132 mg/kg and intravenous injection at 33, 66, 132 mg/kg in
      adjuvant arthritis (AA) rats. In addition, it was found that GE has rapid
      absorption and elimination, low absolute bioavailability, high plasma protein
      binding ability in AA rats after oral administration within the tested dosage
      range. It suggested that GE showed slow distribution into the intra- and
      extracellular space, and the binding rate was not proportionally dependent on
      plasma concentration of GE when the concentration of GE was below 5.0 MUg/mL.

PMID- 25771206
TI  - Drug interactions involving antiepileptic drugs: assessment of the consistency
      among three drug compendia and FDA-approved labels.
AB  - Interactions of antiepileptic drugs (AEDs) with other substances may lead to
      adverse effects and treatment failure. To avoid such interactions, clinicians
      often rely on drug interaction compendia. Our objective was to compare the
      concordance for twenty-two AEDs among three drug interaction compendia
      (Micromedex, Lexi-Interact, and Clinical Pharmacology) and the US Food and Drug
      Administration-approved product labels. For each AED, the overall concordance
      among data sources regarding existence of interactions and their classification
      was poor, with less than twenty percent of interactions listed in all four
      sources. Concordance among the three drug compendia decreased with the fraction
      of the drug excreted unchanged and was greater for established inducers of
      hepatic drug-metabolizing enzymes than for the drugs that are not inducers (R
      square=0.83, P<0.01). For interactions classified as contraindications, major,
      and severe, concordance among the four data sources was, in most cases, less than
      30%. Prescribers should be aware of the differences between drug interaction
      sources of information for both older AEDs and newer AEDs, in particular for
      those AEDs which are not involved in hepatic enzyme-mediated interactions. 

PMID- 25771207
TI  - Involvement of the serotonergic system of the ventral hippocampus (CA3) on
      amnesia induced by ACPA in mice.
AB  - Interactions between the cannabinoid and serotonin systems have been reported in
      many studies. In the present study, we investigated the influence of the
      serotonergic receptor agents on amnesia induced by the cannabinoid CB1 receptor
      agonist, arachydonilcyclopropylamide (ACPA). Bilateral guide-cannulae were
      implanted to allow intra-CA3 microinjection of the drugs. The results showed that
      the intra-peritoneal (i.p.) injection of ACPA induce amnesia but did not alter
      head dip latency, head dip counts, and locomotion. Moreover, intra-CA3 injection
      of M-Chlorophenylbiguanide (M-CHL, a 5-HT3 serotonin receptor agonist), Y-25130
      (a 5-HT3 serotonin receptor antagonist), RS67333 (a 5-HT4 serotonin receptor
      agonist), and RS23597-190 (a 5-HT4 serotonin receptor antagonist) impaired memory
      but have no effect on head dip latency and locomotor activity. In addition, intra
      CA3 injection of Y-25130, RS67333, and RS23597-190 heighten the ACPA-induced
      amnesia and head dip counts while did not alter head dip latency and locomotor
      activity. On the other hand, intra-CA3 microinjection of M-CHL could not modify
      the ACPA-induced amnesia, head dip latency and locomotor activity whereas
      increased head dip counts. It can be concluded that the amnesia induced by i.p.
      administration of ACPA is at least partly mediated through the serotonergic
      receptor mechanism in the CA3 area.

PMID- 25771208
TI  - A mild traumatic brain injury (mTBI) induces secondary attention-deficit
      hyperactivity disorder-like symptomology in young rats.
AB  - Although attention-deficit hyperactivity disorder (ADHD) is commonly reported
      after moderate and severe traumatic brain injury (TBI), research is struggling to
      find a strong link between mild TBI or concussion and ADHD. Epidemiological
      studies often generate conflicting results which may be related to the difficulty
      identifying the lingering symptoms of mTBI, the lack of baseline knowledge and
      the possible exacerbation of pre-existing ADHD symptomology, and/or differential
      diagnostic criteria for secondary ADHD. The purpose of this study was to
      determine if a mild TBI/concussion in the juvenile period (postnatal day 30)
      could induce ADHD-like symptoms in young rodents. Using the Go/No-Go paradigm of
      the 5-choice serial reaction task, sustained attention, impulsivity, and response
      inhibition was measured. The open field was also used to measure activity levels
      at two time points. Animals that experienced an mTBI in the juvenile period
      exhibited ADHD symptomology, with sex-differences present on one of the tasks.
      Significant deficits were identified in sustained attention, response inhibition,
      and impulsivity. Immediately after the mTBI, all rats were hypoactive in the open
      field, and while male animals exhibited a trend toward hyperactivity in the long
      term, females continued to trend toward hypoactivity for the duration of the
      experiment. These findings provide a unique platform upon which preventative and
      therapeutic strategies can be implemented and tested in an effort to improve ADHD
      like symptoms following mTBI.

PMID- 25771210
TI  - How good is that sample? Verifying the integrity of biobanked samples.

PMID- 25771209
TI  - Plasmalogen precursor analog treatment reduces levodopa-induced dyskinesias in
      parkinsonian monkeys.
AB  - L-DOPA-induced dyskinesias (LID) remain a serious obstacle in the treatment of
      Parkinson's disease (PD). The objective of this study was to test a new target
      for treatment of dyskinesias, ethanolamine plasmalogens (PlsEtn). PlsEtn play
      critical roles in membrane structure mediated functions and as a storage depot of
      polyunsaturated fatty acids such as docosahexaenoic acid (DHA, omega-3) known to
      reduce dyskinesias. The motor effect of a daily treatment for 12 days of 1-methyl
      4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) Macaca fascicularis monkeys with DHA
      (100mg/kg) was compared to the DHA-PlsEtn precursor PPI-1011 (50mg/kg). PPI-1011
      and DHA reduced LID while maintaining the antiparkinsonian activity of l-DOPA,
      however the PPI-1011 effect was observed at the first behavioral time point
      analyzed following drug administration (day 2) whereas the effect of DHA was not
      observed until after 10 days of administration. DHA treatment increased plasma
      DHA levels 2-3* whereas PPI-1011 had no effect. DHA and PPI-1011 increased DHA
      PlsEtn levels by 1.5-2* while DHA-phosphatidylethanolamine (PtdEtn) levels
      remained unaffected. DHA treatment also elevated very long chain fatty acid
      containing PtdEtn and reduced non-DHA containing PtdEtn and PlsEtn levels. PPI
      1011 had no effect on these systems. LID scores were inversely correlated with
      serum DHA-PlsEtn/total PlsEtn ratios levels in DHA and PPI-1011 treated monkeys.
      Hence, the antidyskinetic activity of DHA and PPI-1011 in MPTP monkeys appears to
      be associated with the increase of serum DHA-PlsEtn concentrations. This is the
      first study reporting an antidyskinetic response to augmentation of DHA-PlsEtn
      using a plasmalogen precursor thus providing a novel drug target for dyskinesias.

PMID- 25771211
TI  - A Percutaneous Transtubular Middle Fossa Approach for Intracanalicular Tumors.
AB  - OBJECTIVE: In cases of small intracanalicular tumors (<= 1.5 cm), the middle
      fossa approach (MFA) provides the ability for adequate tumor removal with
      preservation of existing auditory function. Application of a minimally invasive
      tubular retractor in this approach may help mitigate the risk of postoperative
      seizures, aphasia, and venous complications by minimizing intraoperative
      retraction of the temporal lobe. We propose a minimally invasive microscopic
      and/or endoscopic percutaneous transtubular MFA for the management of
      intracanalicular tumors. METHODS: Subtemporal keyhole craniectomies were
      performed on 5 preserved cadaveric heads (10 sides), with 6 sides previously
      injected with a synthetic tumor model. A ViewSite Brain Access System tubular
      retractor (Vycor Medical, Inc., Boca Raton, Florida, USA) was used to provide
      minimal temporal retraction and protection of the surrounding anatomy. An
      extradural dissection of the internal auditory canal was performed under
      microscopic and endoscopic visualization with a minimally invasive surgical drill
      and tube shaft instruments, the intracanalicular tumors were removed, and degree
      of resection was assessed. RESULTS: All 10 approaches were completed successfully
      through the tubular retractor with minimal retraction of the temporal lobe.
      Excellent visualization of the structures within the internal auditory canal was
      achieved with both the microscope and 3-dimensional endoscope. On the 6 synthetic
      intracanalicular tumors resected, 5 gross total (Grade I) and 1 near total (Grade
      II) resections were achieved. CONCLUSION: A percutaneous transtubular MFA is a
      feasible minimally invasive option for resection of small intracanalicular tumors
      with potential preservation of auditory function, reduced temporal retraction,
      and enhanced protection of surrounding structures.

PMID- 25771212
TI  - Extended-spectrum beta-lactamase infections during pregnancy: a growing threat.
AB  - Extended-spectrum beta-lactamases (ESBLs) are rapidly evolving plasmid
      transferrable enzymes that confer unique patterns of antibiotic resistance on
      various bacterial species. Such organisms pose special challenges to laboratory
      identification, as well as antibiotic selection, administration, and follow-up.
      Although such infections are increasingly common in the obstetric population,
      issues surrounding ESBLs are not widely recognized by practicing obstetricians,
      and controversies exist regarding diagnosis and management. This article provides
      the practitioner with a summary of clinically pertinent information that will
      assist in the proper care of pregnant patients with ESBL infection. 

PMID- 25771213
TI  - The direct and indirect costs of uterine fibroid tumors: a systematic review of
      the literature between 2000 and 2013.
AB  - This systematic literature review was conducted to summarize the direct and
      indirect costs per patient that are associated with uterine fibroid tumors in
      international studies. A search with predefined search terms was conducted in
      MEDLINE and EMBASE for studies that were published from January 2000 to November
      2013. The review included primary studies that were in English and that reported
      either direct costs (drug costs, procedure costs, and medical service costs) or
      indirect costs (such as productivity loss) among patients with uterine fibroid
      tumors. A total of 26 studies that were identified and included in the data
      extraction included 19 studies in the United States, 2 studies in the
      Netherlands, 1 study each in Germany, China, Italy, and Canada, and 1 study
      reported data that were collected from 3 countries: Germany, France, and England.
      The studies differed substantially in perspectives that were adopted for
      analysis, research designs, data elements that were collected, setting,
      populations, and outcome measurements. Among 3 studies that reported total direct
      costs during the year after uterine fibroid tumor diagnosis, 2 studies reported
      an average of $9473 and $9319 per patient, respectively; 2 studies reported the
      excess costs over controls to be $6076 and $5427, respectively. The indirect
      costs per patient ranged from $2399-15,549, and the excess indirect cost per
      patient over control groups ranged from $323-4824 in the year after the
      diagnosis. The total costs, sum of direct and indirect costs, ranged from $11,717
      25,023 per patient per year, after diagnosis or surgery among patients with
      uterine fibroid tumors. Compared with control subjects, the additional annual
      cost ranged from $2200-15,952 per patient. The results of this systematic
      literature review highlight the substantial direct and indirect costs that are
      associated with uterine fibroid tumors to health care payers and society. The
      large number and the variety of studies identified also emphasize the growing
      awareness of the significant economic impact of uterine fibroid tumors. Current
      gaps that were identified through this review warrant further investigation to
      elucidate fully the economic burden of uterine fibroid tumors, including, but not
      limited to, burden from the patient's perspective and the entirety of indirect
      costs. 

PMID- 25771214
TI  - Diffused sunlight driven highly synergistic pathway for complete mineralization
      of organic contaminants using reduced graphene oxide supported photocatalyst.
AB  - Diffused sunlight is found to be an effective light source for the efficient
      degradation and mineralization of organic pollutant (methyl orange as a probe) by
      sono-photocatalytic degradation using reduced graphene oxide (rGO) supported CuO
      TiO2 photocatalyst. The prepared catalysts are characterized by XRD, XPS, UV-vis
      DRS, PL, photoelectrochemical, SEM-EDS and TEM. A 10 fold synergy is achieved for
      the first time by combining sonochemical and photocatalytic degradation under
      diffused sunlight. rGO loading augments the activity of bare CuO-TiO2 more than
      two fold. The ability of rGO in storing, transferring, and shuttling electrons at
      the heterojunction between TiO2 and CuO facilitates the separation of
      photogenerated electron-hole pairs, as evidenced by the photoluminescence
      results. The complete mineralization of MO and the by-products within a short
      span of time is confirmed by TOC analysis. Further, hydroxyl radical mediated
      degradation under diffused sunlight is confirmed by LC-MS. This system shows
      similar activity for the degradation of methylene blue and 4-chlorophenol
      indicating the versatility of the catalyst for the degradation of various
      pollutants. This investigation is likely to open new possibilities for the
      development of highly efficient diffused sunlight driven TiO2 based
      photocatalysts for the complete mineralization of organic contaminants. 

PMID- 25771215
TI  - Sulfuric acid doped poly diaminopyridine/graphene composite to remove high
      concentration of toxic Cr(VI).
AB  - Sulfuric acid doped diaminopyridine polymers are synthesized in situ on graphene
      oxide surface via mutual oxidation-reduction technique. Exploiting large and
      highly porous surface, we have used this polymer composite as an adsorbent to
      remove high concentration of toxic Cr(VI) from water. It shows very high
      adsorption capacity (609.76 mg g(-1)) during removal process. The composite takes
      only 100 min to remove high concentration of 500 mg L(-1) Cr(VI) from water.
      Interesting features for this material is the enhancement of removal efficiency
      at lower acidic condition due to the formation of acid doped emeraldine salt
      during polymerization. XPS and AAS measurements reveal that our prepared material
      mainly follows reduction mechanism at higher acidic condition while anions
      exchange mechanism at lower acidic condition during the removal experiments. Good
      recycling ability with ~ 92% removal efficiency after fifth cycle is also noticed
      for this material. Easy preparation, superior stability in acidic condition,
      remarkable removal efficiency and excellent recycling ability make this polymer
      composite an efficient material for modern filtration units in waste water
      purification.

PMID- 25771216
TI  - Ultimate selenium(IV) monitoring and removal from water using a new class of
      organic ligand based composite adsorbent.
AB  - This work reports the selenium (Se(IV)) detection and removal from water by
      ligand functionalized organic-inorganic based novel composite adsorbent. The
      composite adsorbent was prepared by direct immobilization of N,N'-di(3
      carboxysalicylidene)-3,4-diamino-5-hydroxypyrazole onto the mesoporous silica
      monolith. The adsorbent exhibited distinct color change in the presence of
      various concentrations of Se(IV). This was characterized by UV-vis spectroscopy,
      and the color change was observed by naked-eye observation. The detection limit
      was determined to be 1.14 MUg/L. The effect of solution pH, interferential metal
      ions, contact time, initial Se(IV) concentration, and adsorbent regeneration were
      evaluated. The maximum sorption capacity was determined based on the initial
      concentration. The data fitted well to the Langmuir isotherm model, and the
      maximum Se(IV) sorption capacity was 111.12 mg/g. The presence of diverse
      competing ions did not affect the Se(IV) sorption capacity, and the adsorbent had
      almost no sorption capacity for these coexisting ions, which suggests the high
      selectivity to Se(IV) ions. The adsorbed Se(IV) was eluted with suitable eluent
      (0.10 M NaOH) and simultaneously regenerated into the initial form for the next
      operation. The excellent reusability of the adsorbent was justified after eight
      consecutive sorption-elution-regeneration cycles. The proposed adsorbent is cost
      effective and environmentally friendly and a potential candidate for treatment of
      water containing Se(IV).

PMID- 25771217
TI  - Foliar uptake and translocation of formaldehyde with Bracket plants (Chlorophytum
      comosum).
AB  - The foliar uptake and transport of formaldehyde into Bracket plants from air via
      leaves and roots to external water was investigated in an air-plant-water system.
      The results indicated that formaldehyde could be quickly taken up by plant
      tissues, and that formaldehyde accumulated in leaves could be released rapidly
      back into air when the formaldehyde level in air was diminished. This rapid
      reversible translocation of formaldehyde between plant leaves and air resulted in
      high formaldehyde concentrations in leaf dews, depending upon exposure levels of
      formaldehyde in air. Meanwhile, formaldehyde could be transported from air to
      plant rhizosphere solution through downward transport. The concentration of
      formaldehyde in rhizosphere solutions increased with exposure time and the
      formaldehyde level in air. The efficiency of the leaf extracts to break down
      formaldehyde increased, probably because of an increase in oxidative potential of
      the leaf extracts. Taken together, the main mechanism of formaldehyde loss in air
      can be attributed to the accumulation by (or breakdown in) plant tissues; the
      removal rate of formaldehyde from air reached 135 MUg h(-1) plant(-1) in the
      experimental condition.

PMID- 25771218
TI  - Development of loop-mediated isothermal amplification (LAMP) assay for the rapid
      detection of Penicillium nordicum in dry-cured meat products.
AB  - The need of powerful diagnostic tools for rapid, simple, and cost-effective
      detection of food-borne fungi has become very important in the area of food
      safety. Currently, several isothermal nucleic acid amplification methods have
      been developed as an alternative to PCR-based analyses. Loop-mediated isothermal
      amplification (LAMP) is one of these innovative methods; it requires neither gel
      electrophoresis to separate and visualize the products nor expensive laboratory
      equipment and it has been applied already for detection of pathogenic organisms.
      In the current study, we developed a LAMP assay for the specific detection of
      Penicillium nordicum, the major causative agent of ochratoxin A contamination in
      protein-rich food, especially dry-cured meat products. The assay was based on
      targeting otapksPN gene, a key gene in the biosynthesis of ochratoxin A (OTA) in
      P. nordicum. Amplification of DNA during the reaction was detected directly in
      tube by color transition of hydroxynaphthol blue from violet to sky blue, visible
      to the naked eye, avoiding further post amplification analyses. Only DNAs
      isolated from several P. nordicum strains led to positive results and no
      amplification was observed from non-target OTA and non OTA-producing strains. The
      assay was able to detect down to 100 fg of purified targeted genomic DNA or 10(2)
      conidia/reaction within 60 min. The LAMP assay for detection and identification
      of P. nordicum was combined with a rapid DNA extraction method set up on serially
      diluted conidia, providing an alternative rapid, specific and sensitive DNA-based
      method suitable for application directly "on-site", notably in key steps of dry
      cured meat production.

PMID- 25771219
TI  - Phage-mediated transfer of a dextranase gene in Lactobacillus sanfranciscensis
      and characterization of the enzyme.
AB  - While phages of lactobacilli are extensively studied with respect to their
      structure and role in the dairy environment, knowledge about phages in bacteria
      residing in sourdough fermentation is limited. Based on the previous finding that
      the Lactobacillus sanfranciscensis phage EV3 carries a putative dextranase gene
      (dex), we have investigated the distribution of similar dex(+) phages in L.
      sanfranciscensis, the chance of gene transfer and the properties of the
      dextranase encoded by phage EV3. L. sanfranciscensis H2A (dex(-)), originally
      isolated from a wheat sourdough, expressed a Dex(+) phenotype upon infection with
      EV3. The dextranase gene was isolated from the transductant and heterologously
      expressed in Escherichia coli. The gene encoded a protein of 801 amino acids with
      a calculated molecular weight (Mw) of 89.09 kDa and a calculated pI of 5.62. Upon
      purification aided by a 6-His tag, enzyme kinetic parameters were determined. The
      Km value was 370 mM, and the Vmax was calculated in about 16 MUmol of glucose
      released from dextran by 1 mg of enzyme in 1 min in a buffer solution at pH 5.0.
      The optimum conditions were 60  degrees C and pH 4.5. The enzyme retained its
      activity for >3h at 60  degrees C and exhibited only 40% activity at 30  degrees
      C; the highest homology of 72% was found to a dextranase gene from Lactobacillus
      fermentum phage phiPYB5. Within 25 L. sanfransiscensis isolates tested, the
      strain 4B5 carried a similar prophage encoding a dextranase gene. Our data
      suggest a phage-mediated transfer of dextranase genes in the sourdough
      environment resulting in superinfection-resistant L. sanfranciscensis Dex(+)
      strains with a possible ecological advantage in dextran-containing sourdoughs.

PMID- 25771220
TI  - Midwives' adoption of the reproductive life plan in contraceptive counselling: a
      mixed methods study.
AB  - STUDY QUESTION: How is the reproductive life plan (RLP) adopted in midwifery
      contraceptive counselling? SUMMARY ANSWER: A majority of midwives adopted the RLP
      in their counselling, had predominantly positive experiences and considered it a
      feasible tool for promoting reproductive health. WHAT IS KNOWN ALREADY: The RLP
      is a health-promoting tool recommended by the Centers for Disease Control and
      Prevention in the USA for improving preconception health. It was recently used in
      a clinical setting in Sweden and was found to increase women's knowledge about
      fertility and to influence women's wishes to have their last child earlier in
      life. STUDY DESIGN, SIZE, DURATION: An exploratory mixed methods study among 68
      midwives who provided contraceptive counselling in primary health care to at
      least 20 women each during the study period. Midwives received an introduction
      and materials for using the RLP in contraceptive counselling. Three months later,
      in the spring of 2014, they were invited to complete a questionnaire and
      participate in a focus group interview about their adoption of the RLP.
      PARTICIPANTS/MATERIALS, SETTING, METHODS: Data collection was through a
      questionnaire (n = 53 out of 68; participation rate 78%) and five focus group
      interviews (n = 22). Participants included both younger and older midwives with
      longer and shorter experiences of contraceptive counselling in public and private
      health care in one Swedish county. Quantitative data were analysed for
      differences between users and non-users, and qualitative data were analysed by
      qualitative content analysis to explore the midwives experiences and opinions of
      using the RLP. MAIN RESULTS AND THE ROLE OF CHANCE: Sixty-eight per cent of
      midwives had used the RLP in their contraceptive counselling. Four categories
      emerged through the focus group interviews: (i) A predominantly positive
      experience; (ii) The RLP-a health-promoting tool; (iii) individual and societal
      factors influence the RLP counselling; and (4) long-term implementation comprises
      opportunities, risks and needs. The most common reason for not using the RLP was
      lack of information. LIMITATIONS, REASONS FOR CAUTION: There was general lack of
      experience of using the RLP with women from different cultural backgrounds, with
      non-Swedish speaking women and, when a partner was present. Due to the non-random
      sample, the limited knowledge about non-responders and a short follow-up period,
      results apply to short-term implementations and might not fully apply to long
      term implementation. WIDER IMPLICATIONS OF THE FINDINGS: The use of RLP in
      contraceptive counselling appears a feasible way of promoting reproductive
      health. Results from the USA and Sweden indicate it is a promising tool for
      midwives and other health professionals involved in reproductive counselling,
      which deserves to be explored in other nations. STUDY FUNDING/COMPETING
      INTERESTS: Grants were received from the Medical Faculty at Uppsala University
      and the European Society of Contraception and Reproductive Health. There are no
      competing interests. TRIAL REGISTRATION NUMBER: N/A.

PMID- 25771221
TI  - The use of unmanned aerial systems for the mapping of legacy uranium mines.
AB  - Historical mining of uranium mineral veins within Cornwall, England, has resulted
      in a significant amount of legacy radiological contamination spread across
      numerous long disused mining sites. Factors including the poorly documented and
      aged condition of these sites as well as the highly localised nature of
      radioactivity limit the success of traditional survey methods. A newly developed
      terrain-independent unmanned aerial system [UAS] carrying an integrated gamma
      radiation mapping unit was used for the radiological characterisation of a single
      legacy mining site. Using this instrument to produce high-spatial-resolution
      maps, it was possible to determine the radiologically contaminated land areas and
      to rapidly identify and quantify the degree of contamination and its isotopic
      nature. The instrument was demonstrated to be a viable tool for the
      characterisation of similar sites worldwide. 

PMID- 25771222
TI  - 210Po and 210Pb trophic transfer within the phytoplankton-zooplankton
      anchovy/sardine food web: a case study from the Gulf of Lion (NW Mediterranean
      Sea).
AB  - The transfer of (210)Po and (210)Pb in the food web of small pelagic fishes (from
      phytoplankton and zooplankton to anchovy Engraulis encrasicolus and sardine
      Sardina pilchardus) is investigated in the Gulf of Lion (GoL). We present
      original data of (210)Po and (210)Pb activity concentrations, C and N stable
      isotope ratios, measured (i) from different size classes of phytoplankton and
      zooplankton during spring and winter in different environments of the GoL, and
      (ii) in two fish species. Significant spatial patterns based on (210)Po, (210)Pb
      activity concentrations and (210)Po/(210)Pb ratios in the different plankton size
      classes are evidenced by hierarchical clustering, both in spring and winter. This
      variability, also observed for C and N stable isotopes ratios, is connected to
      local specific pelagic habitats and hydrodynamics. The sampling strategy suggests
      that (210)Po bioaccumulation in the GoL remains at a constant level from the
      first (dominated by phytoplankton) to the second trophic level (zooplankton),
      while (210)Pb bioaccumulation shows an increase in winter. Based on stable N
      isotope ratios and (210)Po activity concentrations measured in anchovies and
      sardines, we evidence (210)Po bio-magnification along the trophic food web of
      these two planktivorous pelagic fishes. 

PMID- 25771224
TI  - Single nucleotide polymorphism creating a variable upstream open reading frame
      regulates glucocorticoid receptor expression.
AB  - The glucocorticoid and mineralocorticoid receptors are known to play a crucial
      role in cellular responses to acute and chronic stress conditions. However, the
      influence of genetic variants and regulatory mechanisms within the glucocorticoid
      and mineralocorticoid receptor genes NR3C1 and NR3C2 is still incompletely
      understood. We therefore investigated putative upstream open reading frames, a
      motif regulating gene expression, from the 5' untranslated regions of the
      predominant human glucocorticoid receptor gene NR3C1 isoform alpha variant 1 and
      from the human mineralocorticoid receptor NR3C2 variants 1 and 2. The in silico
      analysis displayed one SNP (rs10482612), being present heterozygously in about
      1.2% of the world population and 1.8% of the European population (according to
      the NCBI database), whose minor allele 'A' creates an upstream start codon. Our
      functional analysis performed by reporter gene assay and quantitative real-time
      PCR confirmed that the minor allele 'A' of the SNP rs10482612 can indeed alter
      protein activity of the subsequent gene during baseline conditions and cellular
      stress by creating a functional uORF in the 5'UTR of the NR3C1 transcript variant
      1.

PMID- 25771225
TI  - The effects of iron limitation and cell density on prokaryotic metabolism and
      gene expression: Excerpts from Fusobacterium necrophorum strain 774 (sheep
      isolate).
AB  - Fusobacterium necrophorum is a Gram-negative obligate anaerobe associated with
      several diseases in humans and animals. Despite its increasing clinical
      significance, there is little or no data on the relationship between its
      metabolism and virulence. Previous studies have shown that bacteria grown under
      iron-limitation express immunogenic antigens similar to those generated in vivo.
      Thus, this paper describes the relationship between F. necrophorum subsp.
      necrophorum (Fnn) metabolism and the expression of the encoded putative virulence
      factors under iron-restricted conditions. At the midlog phase, iron limitation
      reduced Fnn growth but the cell density was dependent on the size of the
      inoculum. Preferential utilization of glucose-1-phosphate, d-mannitol and l
      phenylalanine; production of 2-hydroxycaproic acid and termination of dimethyl
      sulphide production were major Fnn response-factors to iron limitation.
      Ultimately, iron restriction resulted in an increased ability of Fnn to
      metabolize diverse carbon sources and in the expression of stress-specific
      virulence factors. Iron starvation in low Fnn cell density was associated with
      the up-regulation of haemagglutinin (HA) and leukotoxin (lktA) genes (2.49 and
      3.72 fold change respectively). However, Fnn encoded Haemolysin (Hly), yebN
      homologue (febN) and tonB homologue, were down-regulated (0.15, 0.79 and 0.33,
      fold changes respectively). Interestingly, cell density appeared to play a
      regulatory role in the final bacteria cell biomass, induction of a metabolic gene
      expression and the expression pattern virulence factors in Fnn suggesting the
      role of a cell density-associated regulatory factor. This report suggest that
      future studies on differential expression of bacterial genes under altered
      environmental condition(s) should consider testing the effect of cell
      concentrations as this is often neglected in such studies. In conclusion, iron
      restriction induces preferential utilization of carbon sources and altered
      metabolism in Fnn with associated changes in the expression pattern of the
      virulence factors.

PMID- 25771223
TI  - The Roles of Left Versus Right Anterior Temporal Lobes in Conceptual Knowledge:
      An ALE Meta-analysis of 97 Functional Neuroimaging Studies.
AB  - The roles of the right and left anterior temporal lobes (ATLs) in conceptual
      knowledge are a source of debate between 4 conflicting accounts. Possible ATL
      specializations include: (1) Processing of verbal versus non-verbal inputs; (2)
      the involvement of word retrieval; and (3) the social content of the stimuli.
      Conversely, the "hub-and-spoke" account holds that both ATLs form a bilateral
      functionally unified system. Using activation likelihood estimation (ALE) to
      compare the probability of left and right ATL activation, we analyzed 97
      functional neuroimaging studies of conceptual knowledge, organized according to
      the predictions of the three specialized hypotheses. The primary result was that
      ATL activation was predominately bilateral and highly overlapping for all
      stimulus types. Secondary to this bilateral representation, there were subtle
      gradations both between and within the ATLs. Activations were more likely to be
      left lateralized when the input was a written word or when word retrieval was
      required. These data are best accommodated by a graded version of the hub-and
      spoke account, whereby representation of conceptual knowledge is supported
      through bilateral yet graded connectivity between the ATLs and various modality
      specific sensory, motor, and limbic cortices. 

PMID- 25771226
TI  - Selection of potential biological control of Exserohilum turcicum with epiphytic
      microorganisms from maize.
AB  - The aims of this study were to select microbial isolates from phyllosphere of
      maize and to examine their antagonistic activity against Exserohilum turcicum.
      Selection was performed through the ability of isolates to compete with the
      pathogen using an index of dominance and to affect growth parameters of E.
      turcicum. Most of the epiphytic populations obtained for the screening were
      bacteria. These isolates were found in the order of 6 log CFU/g of leaf fresh
      weight. According to similar morphological characteristics and staining, 44 out
      of 111 isolates obtained were selected for testing antagonistic effects. At water
      potential, psi, -1.38MPa and -4.19MPa, three Bacillus isolates showed dominance
      at a distance (5/0) and a significant reduction of growth rate of the pathogen.
      Three Bacillus isolates only decreased the growth rate of E. turcicum at 
      1.38MPa. At -4.19MPa the growth rate decreased with three isolates of Pantoea and
      three Bacillus. In this study a negative and significant correlation was observed
      between the growth rate of E. turcicum and the dominance index in the interaction
      of the pathogen with some bacteria. These results show that with decreasing
      growth rate of the pathogen the dominance index of the interaction increases.
      Eleven potential biocontrol agents against E. turcicum were selected.

PMID- 25771227
TI  - Hyperuricemia reflects global Fontan pathophysiology and associates with
      morbidity and mortality in patients after the Fontan operation.
AB  - BACKGROUND: Serum uric acid (UA, mg/dl) levels associate with the pathophysiology
      and prognosis in patients with chronic heart failure. PURPOSE: To clarify the
      clinical significance of hyperuricemia (HUA, UA>7.0) in Fontan patients. METHODS
      AND RESULTS: We prospectively measured UA in 197 child and 102 adult Fontan
      patients and compared the results with the clinical variables, including
      hemodynamics, exercise capacity, and plasma levels of norepinephrine (NE) and
      brain natriuretic peptide, and unscheduled hospitalization (USH), including all
      cause mortality. The mean UA was 5.8 +/- 1.7 and 66 patients (22%, 34% in the
      adults) showed HUA. HUA was associated with lower peak oxygen uptake only in
      adults (r = -0.35, p < 0.0001). In children the use of diuretics, central venous
      pressure, liver enzymes, NE, and plasma creatinine (Cr) independently associated
      with UA. Of those, in addition to hypoxia, the use of diuretics and Cr
      independently predicted HUA (p < 0.05-0.001). In adults, hypoxia, plasma levels
      of sodium and Cr independently determined UA. Of those, hypoxia and hyponatremia
      independently predicted HUA (p < 0.05-0.001). During a follow-up of 49 +/- 27
      months, 67 USH, including 17 deaths, occurred. In all patients, on univariate
      analysis, HUA predicted mortality (hazard ratio: 3.2, 95% confidence interval:
      1.2-8.6, p = 0.0193). HUA predicted USH in all, adult and child Fontan patients
      (p<0.05-0.0001), however, these prognostic values, including for mortality, were
      not independent in the multivariate analyses. CONCLUSIONS: UA reflects global
      postoperative Fontan pathophysiology, including the prognosis, with some
      differences between child and adult patients. However, the prognostic value of
      HUA may be limited in multivariate models in this particular cohort.

PMID- 25771228
TI  - Soluble urokinase plasminogen activator receptor as a prognostic marker of all
      cause and cardiovascular mortality in a black population.
AB  - BACKGROUND: Elevated inflammatory markers such as C-reactive protein (CRP) and
      interleukin-6 (IL-6) are well-known risk factors for cardiovascular mortality.
      The less familiar marker, soluble urokinase plasminogen activator receptor
      (suPAR), is known to predict cancer, infections and all-cause mortality. We
      determined whether suPAR, CRP and IL-6 are predictive of both all-cause and
      cardiovascular mortality in a black population, highly burdened by cardiovascular
      disease and HIV infection. METHODS: We included 1425 black South Africans, of
      which 208 died within five years after baseline data collection. EDTA plasma
      biomarker levels were determined, while all-cause and cardiovascular mortality
      were used as endpoints. RESULTS: At baseline suPAR, CRP and IL-6 were higher in
      non-survivors than in survivors (P<0.001). SuPAR (HR 1.27, 95% CI 1.09-1.48), IL
      6 (HR 1.49, 95% CI 1.24-1.78) and CRP (HR 1.39, 95% CI 1.17-1.65) predicted all
      cause mortality, while only suPAR (HR 1.40, 95% CI 1.04-1.87) and IL-6 (HR 1.61,
      95% CI 1.10-2.35) predicted cardiovascular mortality. The prognostic value of
      suPAR was independent of IL-6 and CRP (P<=0.015). CONCLUSION: SuPAR predicted
      both all-cause and cardiovascular mortality, independent of traditional risk
      factors, HIV and other inflammatory markers, underlining the prognostic value of
      suPAR in a black population.

PMID- 25771229
TI  - Hypertension burden and control in mainland China: Analysis of nationwide data
      2003-2012.
AB  - BACKGROUND: No nationwide survey on hypertension was conducted in China since
      2002. We assessed the prevalence, awareness, treatment, and control of
      hypertension in mainland China and in various regions using nationwide data from
      2003 to 2012. METHODS AND RESULTS: We identified studies that reported age- and
      gender-specific prevalence and/or age-specific awareness, treatment and control
      of hypertension in representative population samples from 31 provinces, using
      China National Knowledge Infrastructure, Wanfang and PubMed, supplemented by a
      manual search of references of retrieved articles. All data were extracted
      independently by two investigators using a standardized data-collection form.
      Overall, 265 million adults (145 million men and 120 million women) had
      hypertension for a prevalence of 26.7% (28.9% among men and 24.5% among women) in
      2010. Among hypertensive patients, only 44.6% were aware of their condition,
      35.2% were taking antihypertensive medication, and 11.2% achieved adequate blood
      pressure control. There were substantial geographic variations in the prevalence
      and control of hypertension. Hypertension prevalence was the highest in east
      region (32.6%) followed by northeast region (31.8%). Worse still, the control
      rate among hypertensive people was very poor in southwest (4.8%) and northeast
      (5.9%) regions. CONCLUSIONS: Hypertension is highly prevalent in mainland China,
      with inadequate awareness, treatment, and control of hypertension. Effective
      strategies are urgently needed in China, especially in the regions with high
      prevalence and low control.

PMID- 25771230
TI  - Endogenous activated angiotensin-(1-7) plays a protective effect against
      atherosclerotic plaques unstability in high fat diet fed ApoE knockout mice.
AB  - BACKGROUND AND OBJECTIVE: We recently found that exogenous angiotensin-(1-7) [Ang
      (1-7)] inhibits Angiotensin II (Ang-II)-induced atherosclerotic lesion formation
      and enhances plaque stability. Our objective was to evaluate the role of
      endogenous activated Ang-(1-7) during atherosclerosis. METHODS AND RESULTS: In
      mice, the effects of endogenous Ang-(1-7) on atherogenesis in early stage and
      plaque stability in late stage were observed in ApoE knockout (ApoE-/-) mice fed
      with a high fat diet. Blockage of endogenous Ang-(1-7) with A779, an Ang-(1-7)
      antagonist, did not increase early plaque lesion formation, however, it
      remarkably enhanced contents of lipids and macrophages and decreased contents of
      vascular smooth muscle cells (VSMCs) and collagens in late lesions. The
      expressions of proinflammatory cytokines, and the expressions and activities of
      matrix metalloproteinases were significantly elevated in A779-treated group than
      those in vehicle-treated group in late lesions. Exogenous Ang-(1-7) treatment
      attenuated early atherosclerotic plaque formation and enhanced late plaques
      stability in this model. The contents of Ang-II and Ang-(1-7) and activity of
      ACE2 in late atherosclerotic plaques were higher than those of early
      atherosclerotic lesions. CONCLUSION: Endogenous activated Ang-(1-7) enhanced late
      atherosclerotic plaques stability but did not affect early atherosclerotic plaque
      formation. Therapies to elevate endogenous Ang-(1-7) may be a potentially
      effective approach to attenuate atherosclerotic plaques vulnerability.

PMID- 25771231
TI  - Acute myocardial infarction due to left anterior descending coronary artery
      dissection after rubber bullet shooting.

PMID- 25771232
TI  - Serum eicosapentaenoic acid to arachidonic acid ratio is associated with cardio
      healthy exceptional longevity.

PMID- 25771233
TI  - Stent thrombosis after vitamin K administration.

PMID- 25771234
TI  - A case of non-compaction ventricular myocardium and multiple coronary artery-to
      right ventricle fistulae.

PMID- 25771235
TI  - Exclusion of a giant aneurysm post-Kawasaki disease with novel polyurethane
      covered stents.

PMID- 25771236
TI  - Prevention of ventricular arrhythmia complicating acute myocardial infarction by
      local cardiac denervation.
AB  - BACKGROUND: Augmentation of sympathetic nerve activity after acute myocardial
      infarction (AMI) contributes to fatal arrhythmia. In this study, we investigated
      whether local ablation of the coronary sinus (CS) and great cardiac vein (GCV)
      peripheral nerves could reduce ventricular arrhythmias (VA) in a canine AMI
      model. METHODS: Twenty-one anesthetized dogs were randomly assigned into the sham
      operated, MI and MI-ablation groups, respectively. The incidence and duration of
      VA were monitored among different groups. The ventricular effective refractory
      period (ERP), the ERP dispersion and the ventricular fibrillation threshold (VFT)
      were measured during the experiments. Norepinephrine (NE) levels in CS blood and
      cardiac tissue were also detected in this study. RESULTS: The incidence and
      duration of VA in MI-ablation group were significantly reduced as compared to the
      MI dogs (p<0.05). Furthermore, local cardiac denervation drastically prolonged
      the ventricular ERP in the ischemia area, decreased the ERP dispersion, and
      reduced NE levels in CS blood (P<0.05). VFT also showed an increased trend in the
      AMI-ablation group. CONCLUSIONS: The results of this study indicate that, in the
      canine AMI model, local ablation of CS and GCV peripheral nerves reduces VA
      occurrence and improves ventricular electrical stability with no obvious effects
      on heart rate, mean arterial pressure and infarct size. This study suggests that
      local cardiac denervation may prevent ventricular arrhythmias complicating AMI.

PMID- 25771237
TI  - Posterior left atrial isolation for atrial fibrillation in left ventricular
      diastolic impairment is associated with better arrhythmia free survival.
AB  - BACKGROUND: Patients with left ventricular diastolic impairment (LVDI) have
      higher rates of arrhythmia recurrence following atrial fibrillation (AF)
      ablation. Past studies have implicated the posterior left atrium (LA) in atrial
      arrhythmia maintenance in conditions that cause LVDI. We prospectively compared
      posterior LA isolation (PLAI) with wide antral isolation (WAI) in patients with
      LVDI having AF ablation. METHODS: We conducted a sub-study of a previously
      published large randomized control study that compared PLAI with WAI. Two hundred
      and twenty consecutive consenting patients referred for catheter ablation of AF
      (paroxysmal 135, persistent 48, long standing persistent 37) were recruited
      (female 43, mean age 59 +/- 10 years). Transthoracic echocardiography identified
      50 (23%) patients with LVDI and preserved left ventricular systolic function
      (ejection fraction >= 50%). Cox regression analysis was utilized to identify
      independent predictors of atrial arrhythmia after ablation. RESULTS: Patients
      were followed for median 4.6 (inter quartile range 4.0-5.5) years. Patients with
      LVDI having PLAI had better arrhythmia free survival than patients randomized to
      conventional ablation (Log rank P=0.028). The only independent predictor of
      recurrence utilizing Cox regression analysis was ablation strategy (2.3 [1.15
      4.74], P=0.026). CONCLUSION: Posterior isolation of the LA results in superior
      atrial arrhythmia free survival in patients with LVDI. Further investigation is
      required to determine potential mechanisms. CLINICAL TRIAL REGISTRATION:
      http://www.anzctr.org.au;ACTRN12606000467538.

PMID- 25771238
TI  - Relative and absolute risks of all-cause and cause-specific deaths attributable
      to atrial fibrillation in middle-aged and elderly community dwellers.
AB  - BACKGROUND: The relative and absolute risks of outcomes other than all-cause
      death (ACD) attributable to atrial fibrillation (AF) stratified age have not been
      sufficiently investigated. METHODS: A prospective study of 23,634 community
      dwellers aged 40 years or older without organic cardiovascular disease (AF=335,
      non-AF=23,299) was conducted. Multivariate-adjusted rates, rate ratios (RRs) and
      excess deaths (EDs) for ACD, cardiovascular death (CVD) and non-cardiovascular
      death (non-CVD), and sex- and age-adjusted RR and ED in middle-aged (40 to 69)
      and elderly (70 years or older) for ACD, CVD, non-CVD, sudden cardiac death
      (SCD), stroke-related death (Str-D), neoplasm-related death (NPD), and infection
      related death (IFD) attributable to AF were estimated using Poisson regression.
      RESULTS: Multivariate-adjusted analysis revealed that AF significantly increased
      the risk of ACD (RR [95% confidence interval]:1.70 [1.23-2.95]) and CVD (3.86
      [2.38-6.27]), but not non-CVD. Age-stratified analysis revealed that AF increased
      the risk of Str-D in middle-aged (14.5 [4.77-44.3]) and elderly individuals (4.92
      [1.91-12.7]), SCD in elderly individuals (3.21 [1.37-7.51]), and might increase
      the risk of IFD in elderly individuals (2.02 [0.80-4.65], p=0.098). The RR of CVD
      was higher in middle-aged versus elderly individuals (RRs, 6.19 vs. 3.57) but the
      absolute risk difference was larger in elderly individuals (EDs: 7.6 vs. 3.0 per
      1000 person-years). CONCLUSIONS: Larger absolute risk differences for ACD and CVD
      attributable to AF among elderly people indicate that the absolute burden of AF
      is higher in elderly versus middle-aged people despite the relatively small RR.

PMID- 25771239
TI  - Association of structural modifications with bioactivity in three new copper(II)
      complexes of Schiff base ligands derived from 5-chlorosalicylaldehyde and amino
      acids.
AB  - Three novel structurally associated copper(II) complexes [Cu(II)(SalCl
      Gly)(H2O)2] (1), [Cu(II)(SalCl-Ala)(H2O)] (2) and [Cu(II)(SalCl
      Gly)(bipy)].0.5H2O (3) (SalCl-Gly=5-chloro-2-hydroxybenzylidene-glycine, SalCl
      Ala=5-chloro-2-hydroxybenzylidene-alanine, bipy=2,2'-bipyridine) have been
      synthesized and characterized by X-ray crystallography, elemental analysis, IR
      and fluorescence spectroscopy. Single-crystal diffraction reveals that complex 1
      is an infinite 1D zigzag chain in which SalCl-Gly serves as both a chelating and
      a bridging ligand, while complexes 2 and 3 are mononuclear. Cu(II) ions in
      complexes 1-3 exhibit distorted quasi-hexacoordinated octahedral,
      tetracoordinated square planar, and pentacoordinated square pyramid geometry,
      respectively. Their interactions with calf thymus DNA (CT-DNA) have been
      investigated by viscosity measurements and fluorescence spectroscopy. The
      apparent binding constant (Kapp) values for 1-3 are 1.02*10(5), 0.98*10(5) and
      1.57*10(5)M(-1), respectively. All complexes displayed efficient oxidative
      cleavage of supercoiled DNA in the presence of H2O2. Complex 2, whose ligand can
      be regarded as a methyl-modification of SalCl-Gly of 1, showed a reduced DNA
      cleavage activity and a little-changed DNA-binding ability compared with 1. While
      attaching a 2,2'-bipyridine group to 1, the resulting complex 3 was conferred an
      enhanced intercalation into DNA. Moreover, cytotoxicity studies of three
      complexes against HepG-2 (human liver hepatocellular carcinoma) and NCI-H460
      (human large-cell lung carcinoma) cells indicated that, thereto, complex 3
      possessed the highest inhibition on viability of tested cells. 

PMID- 25771240
TI  - Choosing Wisely revisited: finally the support we have been waiting for in
      geriatrics.

PMID- 25771241
TI  - Susceptibility of gametes and embryos of the eastern oyster, Crassostrea
      virginica, to Karenia brevis and its toxins.
AB  - The bivalve mollusc, Crassostrea virginica, is frequently exposed to blooms of
      Karenia brevis along the west coast of Florida during periods of spawning and
      early larval development. A continuous 4-day exposure of gametes and 2-4 cell
      stage embryos of C. virginica to whole-cell and culture filtrate of K. brevis at
      500 and 5000 cells mL(-1), was followed by a 4-day 'recovery' period. Larval
      growth, percent of normal, abnormal and dead larvae, and the presence of food in
      the larval gut were measured throughout the exposure period. Results suggest that
      negative effects mainly occur during embryogenesis and early development. Damage
      to feeding apparatus/gut may occur during embryonic development or exposure to
      toxins may act as a feeding deterrent on non-toxic algae. Following 2-h in vitro
      exposure of gametes, differences in oocyte and sperm cell parameters were
      investigated using flow cytometry. The reduced sperm viability in the whole-cell
      5000 cells mL(-1) treatment suggests the involvement of extracellular brevetoxins
      (PbTx) and perhaps other harmful, uncharacterized compounds associated with the
      K. brevis cell membrane. The cumulative effects of reduced sperm viability,
      fertilization success, embryonic and larval survival, and the near-annual
      exposure to blooms of K. brevis could cause significant bottlenecks on oyster
      recruitment.

PMID- 25771242
TI  - Snake venomics of monocled cobra (Naja kaouthia) and investigation of human IgG
      response against venom toxins.
AB  - The venom proteome of the monocled cobra, Naja kaouthia, from Thailand, was
      characterized by RP-HPLC, SDS-PAGE, and MALDI-TOF-TOF analyses, yielding 38
      different proteins that were either identified or assigned to families.
      Estimation of relative protein abundances revealed that venom is dominated by
      three-finger toxins (77.5%; including 24.3% cytotoxins and 53.2% neurotoxins) and
      phospholipases A2 (13.5%). It also contains lower proportions of components
      belonging to nerve growth factor, ohanin/vespryn, cysteine-rich secretory
      protein, C-type lectin/lectin-like, nucleotidase, phosphodiesterase,
      metalloproteinase, l-amino acid oxidase, cobra venom factor, and
      cytidyltransferase protein families. Small amounts of three nucleosides were also
      evidenced: adenosine, guanosine, and inosine. The most relevant lethal
      components, categorized by means of a 'toxicity score', were alpha-neurotoxins,
      followed by cytotoxins/cardiotoxins. IgGs isolated from a person who had
      repeatedly self-immunized with a variety of snake venoms were immunoprofiled by
      ELISA against all venom fractions. Stronger responses against larger toxins, but
      lower against the most critical alpha-neurotoxins were obtained. As expected, no
      neutralization potential against N. kaouthia venom was therefore detected.
      Combined, our results display a high level of venom complexity, unveil the most
      relevant toxins to be neutralized, and provide prospects of discovering human
      IgGs with toxin neutralizing abilities through use of phage display screening. 

PMID- 25771243
TI  - Recombinant human HSP60 produced in ClearColiTM BL21(DE3) does not activate the
      NFkappaB pathway.
AB  - HSP60, an intracellular molecular chaperone has been largely described as an
      alarmin or damage-associated molecular pattern when released outside the cell.
      HSP60 has been reported as a possible ligand of TLR2 or TLR4 inducing NFkappaB
      dependant signaling pathway leading to cytokine secretion. However, recent
      publications suggested that HSP60 could not act as an activator of TLR4 by
      itself. The observed effect could be due to the presence of endotoxin in HSP60
      preparation especially LPS. In order to clarify the controversy, we produced
      recombinant human HSP60 in two different strains of Escherichia coli, standard
      strain for protein overproduction, BL21(DE3), and the new ClearColi BL21(DE3)
      strain which lacks LPS-activity through TLR4. Undoubtedly, we have shown that
      recombinant HSP60 by itself was not able to induce NFkappaB-dependant signaling
      pathway in a model of THP1 monocyte cell line. Our data suggest that HSP60 needs
      either pathogen-associated molecules, specific post-translational modification
      and/or other host factors to activate immune cells via NFkappaB activation.

PMID- 25771244
TI  - Characterization of Lactobacillus isolated from dairy samples for probiotic
      properties.
AB  - In the present study twelve Lactobacillus isolates (LBS 1-LBS 12) were
      characterized for probiotic properties. Out of the twelve, eight isolates (LBS 1
      6, 8 and 11) were bile resistant (survival > 50% at 0.3% bile salt w/v) and five
      isolates (LBS 1, 2, 5, 6 and 11) were found acid pH value resistant (survival >
      50% at pH 3). All twelve isolates inhibited the growth of Staphylococcus aureus
      whereas isolate LBS 2 also inhibited the growth of Escherichia coli and
      Salmonella typhimurium. Antibiotic susceptibility testing of isolates was also
      performed and isolate LBS 2 was selected for further study based on its broad
      spectrum effect in clinical pathogen inhibition. LBS 2 was characterized
      phenotypically at Institute of Microbial Technology (IMTECH), Chandigarh, India
      and was confirmed as Lactobacillus rhamnosus by 16S rDNA sequencing and
      subsequent analysis using BLAST. The gene sequence was deposited in GenBank with
      accession number KJ562858. Scanning electron microscopy (SEM) study was used to
      study in vitro epithelial cell adherence and bile salt effect on isolate LBS 2.
      Epithelial cells adherence assay showed positive results and surface roughness of
      LBS 2 increased with increase in bile salt (0.15-0.45% w/v). 

PMID- 25771245
TI  - Long-term Outcomes of Patients With Normal or Minor Motor Function Abnormalities
      Detected by High-resolution Esophageal Manometry.
AB  - BACKGROUND & AIMS: High-resolution manometry (HRM) expands recognition of minor
      esophageal motor abnormalities, but the clinical significance of these is
      unclear. We aimed to determine the outcomes of minor esophageal motor
      abnormalities. METHODS: We reviewed HRM tracings from patients who underwent
      esophageal manometry at Northwestern Memorial Hospital from July 2004 through
      October 2005 by using the Chicago classification (version 2.0). We identified 301
      patients with normal findings or minor manometric abnormalities (weak
      peristalsis, hypertensive peristalsis, frequent failed peristalsis, or rapid
      contractions with normal latency). Ninety-eight patients participated in a phone
      survey in which they were asked questions from the impact dysphagia questionnaire
      (mean follow-up period, 6 years 5 months). RESULTS: Of 301 patients assessed, 166
      had normal findings from HRM, 82 had weak peristalsis, 34 had hypertensive
      peristalsis, 17 had frequent failed peristalsis, and 2 had rapid contractions
      with normal latency. The primary indications for HRM of dysphagia (44%) and
      gastroesophageal reflux disease (63%) were unrelated to manometric findings.
      There were no endoscopic or videofluoroscopic differences between patients with
      minor manometric abnormalities. Of 98 patients with follow-up, findings from HRM
      were normal in 63, weak peristalsis was observed in 23, hypertensive peristalsis
      was observed in 10, and frequent failed peristalsis was observed in 2. No
      patients underwent surgical myotomy, pneumatic dilation, or botulinum toxin
      injection. Use of proton pump inhibitors and rates of fundoplication were
      similar, regardless of manometric findings. Sixteen patients (16%) had
      significant dysphagia at follow-up; hypertensive peristalsis was the most likely
      to be symptomatic. CONCLUSIONS: Patients with normal and minor esophageal motor
      abnormalities report minimal symptoms and have few medical interventions related
      to esophageal dysfunction during long-term follow-up. Therefore, identification
      of normal and minor motor function is likely a good prognostic indicator.

PMID- 25771246
TI  - Inflammatory Bowel Disease Environmental Risk Factors: A Population-Based Case
      Control Study of Middle Eastern Migration to Australia.
AB  - BACKGROUND & AIMS: The incidences of the inflammatory bowel diseases (IBDs)
      Crohn's disease (CD) and ulcerative colitis (UC) are increasing, indicating gene
      environment interactions. Migrants from low-IBD-prevalence countries to a high
      prevalence country may help identify the relative contribution of environmental
      risk factors compared with native Caucasians. METHODS: This prospective case
      control study evaluated IBD environmental risk factors of Middle Eastern migrants
      (MEM) in Australia compared with matched Caucasian IBD subjects, MEM controls,
      Caucasian controls, and controls in the Middle East using adjusted odds ratios
      (aOR). RESULTS: A total of 795 subjects were recruited: 154 MEM cases (75 CD; 79
      UC), 153 MEM controls, 162 Caucasian cases (85 CD; 77 UC), 173 Caucasian
      controls, and 153 controls in Lebanon. Smoking increased CD risk in MEM and
      Caucasians and reduced UC risk in Caucasians (aOR, 0.77; 95% CI, 0.41-0.98) but
      not MEM (aOR, 1.45; 95% CI, 0.80-2.62). Antibiotic use reduced the risk of MEM CD
      (aOR, 0.27; 95% CI, 0.11-0.67) and UC (aOR, 0.38; 95% CI, 0.18-0.80), but
      increased the risk in Caucasians (CD: aOR, 5.24; 95% CI, 2.13-12.90; and UC: aOR,
      6.82; 95% CI, 2.67-17.38). Most hygiene markers (rural dwelling, pet ownership,
      pet feeding, and farm animal contact) reduced CD and UC risk in MEM (P < .05). In
      contrast, in Caucasians these hygiene markers lacked significance. Other
      significant risk factors include IBD family history, appendectomy, tonsillectomy,
      and breastfeeding. CONCLUSIONS: Differential IBD environmental risk factors exist
      between migrants and native Caucasians, indicating a dynamic interplay between
      environmental factors and IBD risk for immigrants that is distinct to those
      factors most relevant in native Caucasians.

PMID- 25771247
TI  - MicroRNA-21 expression and susceptibility to HPV-induced carcinogenesis - role of
      microenvironment in K14-HPV16 mice model.

PMID- 25771248
TI  - Linalool and beta-pinene exert their antidepressant-like activity through the
      monoaminergic pathway.
AB  - AIMS: Linalool and beta-pinene are two volatile monoterpenes that possess
      antidepressant-like activity. These are components of many aromatic plants used
      in folk medicine around the world to relieve anxiety and depression. In this
      contribution, we focused on examining the mechanism of action of these compounds.
      MAIN METHODS: We used mice in the forced swimming test (FST) and antagonist drugs
      (i.p.) to receptors related to the depression process such as 5-HT1A. To assess
      the possible contribution of the serotoninergic system, animals were pre-treated
      with WAY 100635 (a 5-HT1A receptor antagonist) and PCPA (a serotonin synthesis
      inhibitor).To assess the participation of the noradrenergic system, the animals
      were pre-treated with yohimbine (an alpha2 receptor antagonist), propranolol (a
      beta receptor antagonist) and neurotoxin DSP-4 (a noradrenergic neurotoxin). In
      the dopaminergic system, we used SCH23390 (a D1 receptor antagonist). KEY
      FINDINGS: WAY 100635 blocked the antidepressant-like effect of linalool and beta
      pinene. In contrast, pretreatment of mice with PCPA did not modify reductions in
      the immobility time elicited by the two monoterpenes. The yohimbine modified the
      effect of linalool on immobility time. Propranolol and neurotoxin DSP-4 reversed
      the anti-immobility effect of beta-pinene; also, SCH23390 blocked the
      antidepressant-like effect of beta-pinene. SIGNIFICANCE: Our results indicate
      that linalool and beta-pinene produce an antidepressant-like effect through
      interaction with the monoaminergic system.

PMID- 25771249
TI  - A 2 year multidomain intervention of diet, exercise, cognitive training, and
      vascular risk monitoring versus control to prevent cognitive decline in at-risk
      elderly people (FINGER): a randomised controlled trial.
AB  - BACKGROUND: Modifiable vascular and lifestyle-related risk factors have been
      associated with dementia risk in observational studies. In the Finnish Geriatric
      Intervention Study to Prevent Cognitive Impairment and Disability (FINGER), a
      proof-of-concept randomised controlled trial, we aimed to assess a multidomain
      approach to prevent cognitive decline in at-risk elderly people from the general
      population. METHODS: In a double-blind randomised controlled trial we enrolled
      individuals aged 60-77 years recruited from previous national surveys. Inclusion
      criteria were CAIDE (Cardiovascular Risk Factors, Aging and Dementia) Dementia
      Risk Score of at least 6 points and cognition at mean level or slightly lower
      than expected for age. We randomly assigned participants in a 1:1 ratio to a 2
      year multidomain intervention (diet, exercise, cognitive training, vascular risk
      monitoring), or a control group (general health advice). Computer-generated
      allocation was done in blocks of four (two individuals randomly allocated to each
      group) at each site. Group allocation was not actively disclosed to participants
      and outcome assessors were masked to group allocation. The primary outcome was
      change in cognition as measured through comprehensive neuropsychological test
      battery (NTB) Z score. Analysis was by modified intention to treat (all
      participants with at least one post-baseline observation). This trial is
      registered at ClinicalTrials.gov, number NCT01041989. FINDINGS: Between Sept 7,
      2009, and Nov 24, 2011, we screened 2654 individuals and randomly assigned 1260
      to the intervention group (n=631) or control group (n=629). 591 (94%)
      participants in the intervention group and 599 (95%) in the control group had at
      least one post-baseline assessment and were included in the modified intention-to
      treat analysis. Estimated mean change in NTB total Z score at 2 years was 0.20
      (SE 0.02, SD 0.51) in the intervention group and 0.16 (0.01, 0.51) in the control
      group. Between-group difference in the change of NTB total score per year was
      0.022 (95% CI 0.002-0.042, p=0.030). 153 (12%) individuals dropped out overall.
      Adverse events occurred in 46 (7%) participants in the intervention group
      compared with six (1%) participants in the control group; the most common adverse
      event was musculoskeletal pain (32 [5%] individuals for intervention vs no
      individuals for control). INTERPRETATION: Findings from this large, long-term,
      randomised controlled trial suggest that a multidomain intervention could improve
      or maintain cognitive functioning in at-risk elderly people from the general
      population. FUNDING: Academy of Finland, La Carita Foundation, Alzheimer
      Association, Alzheimer's Research and Prevention Foundation, Juho Vainio
      Foundation, Novo Nordisk Foundation, Finnish Social Insurance Institution,
      Ministry of Education and Culture, Salama bint Hamdan Al Nahyan Foundation, Axa
      Research Fund, EVO funding for University Hospitals of Kuopio, Oulu, and Turku
      and for Seinajoki Central Hospital and Oulu City Hospital, Swedish Research
      Council, Swedish Research Council for Health, Working Life and Welfare, and af
      Jochnick Foundation.

PMID- 25771252
TI  - Thematic Issue: Rheumatology: An Evolutionary force in Biologics.

PMID- 25771251
TI  - Beyond the HPA-axis: The role of the gonadal steroid hormone receptors in
      modulating stress-related responses in an animal model of PTSD.
AB  - The hypothalamic-pituitary-adrenal (HPA) axis, which plays a major role in the
      response to stress, and the hypothalamic-pituitary-gonadal (HPG) axis are closely
      linked with the ability to inhibit the other. Testosterone, a product of the HPG,
      has many beneficial effects beyond its functions as a sex hormone including anti
      anxiety properties. In this study we examined the effect of stress exposure on
      gonadal hormones, and their efficacy in modulating anxiety-like response in an
      animal model of PTSD. Male rats were exposed to predator scent stress, followed
      by analysis of brain expression of androgen receptor (AR) receptor and estrogen
      receptor alpha (ERalpha). The behavioral effects of immediate treatment with
      testosterone, testosterone receptor antagonist (flutamide) or vehicle were
      evaluated using the elevated plus-maze, acoustic startle response and trauma-cue
      response. Levels of circulating corticosterone and testosterone were also
      measured after treatment. The behavioral effects of delayed testosterone
      treatment were explored in the same manner. We report that animals whose behavior
      was extremely disrupted (EBR) selectively displayed significant down-regulation
      of AR and ERalpha in the hippocampus. Immediate treatment with flutamide or
      delayed treatment with testosterone significantly increased prevalence rates of
      minimal behavioral response (MBR) and decreased prevalence of EBR with favorable
      behavioral results. Testosterone levels were higher in control un-exposed
      animals, while corticosterone was higher in control exposed animals. This study
      suggests that gonadal steroid hormones are involved in the neurobiological
      response to predator scent stress and thus warrant further study as a potential
      therapeutic avenue for the treatment of anxiety-related disorders. 

PMID- 25771253
TI  - Effects of some chemical surface modifications on resin zirconia adhesion.
AB  - OBJECTIVES: To evaluate the effects of various chemical surface modifications on
      adhesion between zirconia and resin adhesive. MATERIAL AND METHODS: Pre-sintered
      zirconia discs were sectioned from commercial cylindrical blocks and polished
      with abrasive papers under running tap water. All the discs were randomly divided
      into five study groups according to the methods of surface treatment, including:
      the control group (fully sintered, without any modification), group S (fully
      sintered and sandblasted with silica coated alumina particles), group HN (fully
      sintered and etched with a blend of mineral acid solution at 100  degrees C for
      25 min), group HF (fully sintered and etched with 48% hydrofluoric acid solution
      at 100  degrees C for 25 min), and group Si (coated with silica particles and
      then fully sintered). The mean value of surface roughness was evaluated before
      further treatment. Resin stubs (3.6mm in diameter and 3mm in height) were adhered
      and light cured on each zirconia disc after the application of a silane coupling
      agent. In each group, all the samples were further divided into three subgroups
      with each n=12, one for the measurement of initial adhesion strength (shear bond)
      value and the other two were tested after thermal cycling for 10,000 and 20,000
      cycles, respectively. The results were analyzed with two-way ANOVA and Turkey HSD
      (p<0.05). XRD technique was utilized in the examination of zirconia surface
      crystallinity. The morphological appearance of zirconia surface after surface
      treatment was observed with SEM. RESULTS: The control group showed the lowest
      initial shear bond strength (SBS) value (16.8 +/- 2.4 MPa) and did not survive
      the aging treatments. All the investigated surface treatments improved resin
      zirconia bond strength significantly, the group S displaying the highest initial
      value of 25.1 +/- 2.7 MPa. However, the highest resistance to the aging effects
      of thermal cycling was found in group Si. It was further shown in the XRD
      examination that only the grit-blasting caused the crystalline transformation
      from tetragonal phase to monoclinic phase (T -> M). On the other hand, such a
      phase transformation could not be detected in all the other four groups.
      SIGNIFICANCE: Resin zirconia adhesion could be effectively improved by both HF
      etching and silica coating on zirconia surface, without leading to a T -> M
      crystalline phase transformation.

PMID- 25771254
TI  - Micro-scratch and corrosion behavior of functionally graded HA-TiO2
      nanostructured composite coatings fabricated by electrophoretic deposition.
AB  - In the present study, functionally graded coatings of HA/TiO2 nanoparticles and
      HA-TiO2 nanocomposite coatings with 0, 10 and 20 wt% of TiO2 were fabricated by
      electrophoretic deposition on Ti-6Al-4V substrate. The functionally graded
      structure of HA/TiO2 coatings was formed by gradual addition of HA suspension
      into the deposition cell containing TiO2 nanoparticles. Micro-scratch test
      results showed the highest critical distances of crack initiation and
      delamination, normal load before failure and critical contact pressures for
      functionally graded coating. It was observed that the improvement of adhesion
      strength and fracture toughness of functionally graded coatings would be due to
      the reduction of thermal expansion coefficient mismatch between Ti-6Al-4V
      substrate and HA. The results of potentiodynamic polarization measurements showed
      that the graded structure of the coating could efficiently increase the corrosion
      resistance of substrate.

PMID- 25771255
TI  - Creep-assisted slow crack growth in bio-inspired dental multilayers.
AB  - Ceramic crown structures under occlusal contact are often idealized as flat
      multilayered structures that are deformed under Hertzian contact loading.
      Previous models treated each layer as linear elastic materials and resulted in
      differences between the measured and predicted critical loads. This paper
      examines the combined effects of creep (in the adhesive and substrate layers) and
      creep-assisted slow crack growth (in the ceramic layer) on the contact-induced
      deformation of bio-inspired, functionally graded multilayer (FGM) structures and
      the conventional tri-layers. The time-dependent moduli of each of the layers were
      determined from constant load creep tests. The resulting modulus-time
      characteristics were modeled using Prony series. These were then incorporated
      into a finite element model for the computation of stress distributions in the
      sub-surface regions of the top ceramic layer, in which sub-surface radial cracks,
      are observed as the clinical failure mode. The time-dependent stresses are
      incorporated into a slow crack growth (SCG) model that is used to predict the
      critical loads of the dental multilayers under Hertzian contact loading. The
      predicted loading rate dependence of the critical loads is shown to be consistent
      with experimental results. The implications of the results are then discussed for
      the design of robust dental multilayers. 

PMID- 25771256
TI  - Experimental study on multi-step creep properties of rat skins.
AB  - Tension, single-step creep, and multi-step creep of rat skins at room temperature
      were experimentally studied. We studied the effects of loading histories of high
      stress creep, low stress creep, and stress relaxation on multi-step creep.
      Microstructure of rat skins after prescribed tests were observed microscopically
      with the help of standard hematoxylin and eosin (H&E). The void ratios were also
      analyzed. The loading histories of high stress creep, low stress creep, and
      stress relaxation have significant influence on multi-step creep. We found that
      the creep strain and its rate in the steady-state stage and the creep-fatigue
      life of rat skins are sensitive to creep stress. Low stress creep after the
      loading history of high stress creep is characterized as a recovery of strain and
      a zero strain rate. Both the loading history of low stress creep and stress
      relaxation act as a recovery in multi-step creep, and they are driven by a same
      mechanism in the creep strain and the void ratio of rat skins. The loading
      history, of which sequence is as followings successively: low stress creep,
      stress relaxation, and high stress creep, helps to obtain the largest creep
      strain at the lowest void ratio. 

PMID- 25771257
TI  - Tribocorrosion behavior of beta titanium biomedical alloys in phosphate buffer
      saline solution.
AB  - The tribo-electrochemical behavior of different beta titanium alloys for
      biomedical applications sintered by powder metallurgy has been investigated.
      Different mechanical, electrochemical and optical techniques were used to study
      the influence of the chemical composition, Sn content, and the electrochemical
      conditions on the tribocorrosion behavior of those alloys Ti30NbxSn alloys (where
      "x" is the weight percentage of Sn content, 2% and 4%). Sn content increases the
      active and passive dissolution rate of the titanium alloys, thus increasing the
      mechanically activated corrosion under tribocorrosion conditions. It also
      increases the mechanical wear of the alloy. Prevailing electrochemical conditions
      between -1 and 2V influences the wear accelerated corrosion by increasing it with
      the applied potential and slightly increases the mechanical wear of Ti30Nb4Sn.
      Wear accelerated corrosion can be predicted by existing models as a function of
      electrochemical and mechanical parameters of the titanium alloys. 

PMID- 25771258
TI  - Critical buckling pressure in mouse carotid arteries with altered elastic fibers.
AB  - Arteries can buckle axially under applied critical buckling pressure due to a
      mechanical instability. Buckling can cause arterial tortuosity leading to flow
      irregularities and stroke. Genetic mutations in elastic fiber proteins are
      associated with arterial tortuosity in humans and mice, and may be the result of
      alterations in critical buckling pressure. Hence, the objective of this study is
      to investigate how genetic defects in elastic fibers affect buckling pressure. We
      use mouse models of human disease with reduced amounts of elastin (Eln+/-) and
      with defects in elastic fiber assembly due to the absence of fibulin-5 (Fbln5-/
      ). We find that Eln+/- arteries have reduced buckling pressure compared to their
      wild-type controls. Fbln5-/- arteries have similar buckling pressure to wild-type
      at low axial stretch, but increased buckling pressure at high stretch. We fit
      material parameters to mechanical test data for Eln+/-, Fbln5-/- and wild-type
      arteries using Fung and four-fiber strain energy functions. Fitted parameters are
      used to predict theoretical buckling pressure based on equilibrium of an
      inflated, buckled, thick-walled cylinder. In general, the theoretical predictions
      underestimate the buckling pressure at low axial stretch and overestimate the
      buckling pressure at high stretch. The theoretical predictions with both models
      replicate the increased buckling pressure at high stretch for Fbln5-/- arteries,
      but the four-fiber model predictions best match the experimental trends in
      buckling pressure changes with axial stretch. This study provides experimental
      and theoretical methods for further investigating the influence of genetic
      mutations in elastic fibers on buckling behavior and the development of arterial
      tortuosity. 

PMID- 25771259
TI  - The effect of polymerization mode on monomer conversion, free radical entrapment,
      and interaction with hydroxyapatite of commercial self-adhesive cements.
AB  - OBJECTIVES: This study evaluated the degree of conversion, the free radical
      entrapment, and the chemical interaction of self-adhesive resin cements mixed
      with pure hydroxyapatite, as a function of the polymerization activation mode
      among a variety of commercial self-adhesive cements. MATERIALS AND METHODS: Four
      cements (Embrace WetBond, MaxCem Elite, Bifix SE, and RelyX U200) were mixed,
      combined with hydroxyapatite, dispensed into molds, and distributed into three
      groups, according to polymerization protocols: IP (photoactivation for 40s); DP
      (delayed photoactivation, 10 min self-curing plus 40s light-activated); and CA
      (chemical activation, no light exposure). Infrared (IR) spectra were obtained and
      monomer conversion (%) was calculated by comparing the aliphatic-to-aromatic IR
      absorption peak ratio before and after polymerization (n=10). The free radical
      entrapment values of the resin cements were characterized using Electron
      Paramagnetic Resonance (EPR) and the concentration of spins (number of
      spins/mass) calculated (n=3). Values were compared using two-way ANOVA and
      Tukey's post-hoc test (alpha=5%). X-ray diffraction (XRD) characterized the
      crystallinity of hydroxyapatite as a function of the chemical interactions with
      the resin cements. RESULTS: The tested parameters varied as a function of resin
      cement and polymerization protocol. Embrace WetBond and RelyX U200 demonstrated
      dependence on photoactivation (immediate or delayed), whereas MaxCem Elite
      exhibited dependence on the chemical activation mode. Bifix SE presented the best
      balance based on the parameters analyzed, irrespective of the activation
      protocol. CONCLUSIONS: Choice of polymerization protocol affects the degree of
      conversion, free radical entrapment, and the chemical interaction between
      hydroxyapatite and self-adhesive resin cement mixtures.

PMID- 25771260
TI  - EMA and national drug agencies: cooperation or competition?

PMID- 25771262
TI  - Update on the etiology of revision TKA -- Evident trends in a retrospective
      survey of 1449 cases.
AB  - BACKGROUND: A working and complete knowledge of the different causes of
      dysfunction and pain after TKA is essential for the ability to correctly
      determine the cause of failure and to address this problem specifically. The
      purpose of this study was to update the etiology of implant failure. New
      diagnosis and current trends should be displayed. METHODS: All TKA revisions
      performed in our institution between 2001 and 2010 were reviewed retrospectively.
      Patient demographics and the precise indication for the surgery were documented.
      Descriptive statistical analyses and association analyses of both the diagnosis
      and patient demographics were performed. RESULTS: Within our collective of 1449
      revision TKA a total of 40 different pathologies leading to revision surgery were
      identified and categorized. Overall 68.5% of the revisions were categorized
      aseptic, 31.5% as septic implant failure. Some recently debated diagnoses like
      low-grade-infection showed a high increase in incidence whereas classic failure
      mechanisms like polyethylene wear showed a decrease over the time. CONCLUSION: We
      believe that this study successfully updates the current knowledge of different
      failure mechanisms in revision TKA, which have to be considered on dysfunction or
      pain after surgery. We were able to evaluate the clinical relevance of each
      pathology and could shift from implant related problems like wear to more
      surgical problems like instability and or malalignment over the last years. With
      a higher alertness to chronic low-grade-infections the incidence of infection is
      even increasing. LEVEL OF EVIDENCE: Level II, economic and decision analysis.

PMID- 25771261
TI  - Dengue on islands: a Bayesian approach to understanding the global ecology of
      dengue viruses.
AB  - BACKGROUND: Transmission of dengue viruses (DENV), the most common arboviral
      pathogens globally, is influenced by many climatic and socioeconomic factors.
      However, the relative contributions of these factors on a global scale are
      unclear. METHODS: We randomly selected 94 islands stratified by socioeconomic and
      geographic characteristics. With a Bayesian model, we assessed factors
      contributing to the probability of islands having a history of any dengue
      outbreaks and of having frequent outbreaks. RESULTS: Minimum temperature was
      strongly associated with suitability for DENV transmission. Islands with a
      minimum monthly temperature of greater than 14.8 degrees C (95% CI: 12.4-16.6
      degrees C) were predicted to be suitable for DENV transmission. Increased
      population size and precipitation were associated with increased outbreak
      frequency, but did not capture all of the variability. Predictions for 48 testing
      islands verified these findings. CONCLUSIONS: This analysis clarified two key
      components of DENV ecology: minimum temperature was the most important
      determinant of suitability; and endemicity was more likely in areas with high
      precipitation and large, but not necessarily dense, populations. Wealth and
      connectivity, in contrast, had no discernable effects. This model adds to our
      knowledge of global determinants of dengue risk and provides a basis for
      understanding the ecology of dengue endemicity.

PMID- 25771263
TI  - Effectiveness of a perinatal and pediatric End-of-Life Nursing Education
      Consortium (ELNEC) curricula integration.
AB  - BACKGROUND: Educational practices and national guidelines for best practices of
      providing palliative care to children and their families have been developed and
      are gaining support; however, the dissemination of those practices lags behind
      expectations. Incorporating education for pediatric palliative care into nursing
      pre-licensure programs will provide guidelines for best practices with
      opportunities to enact them prior to graduation. OBJECTIVE: To evaluate the
      effect of an integrated curriculum for palliative care on nursing students'
      knowledge. DESIGN: Matched pretest-posttest. SETTING: One private and one public
      university in the northeastern United States. PARTICIPANTS: Two groups of
      baccalaureate nursing students, one exposed to an integrated curriculum for
      palliative care and one without the same exposure. METHODS: Pre-testing of the
      students with a 50-item multiple choice instrument prior to curriculum
      integration and post-testing with the same instrument at the end of the term.
      RESULTS: This analysis demonstrated changes in knowledge scores among the
      experimental (n=40) and control (n=19) groups that were statistically significant
      by time (Wilks' Lambda=.90, F(1, 57)=6.70, p=.012) and study group (Wilks'
      Lambda=.83, F(1, 57)=11.79, p=.001). CONCLUSIONS: An integrated curriculum for
      pediatric and perinatal palliative and end-of-life care can demonstrate an
      increased knowledge in a small convenience sample of pre-licensure baccalaureate
      nursing students when compared to a control group not exposed to the same
      curriculum. Future research can examine the effect on graduates' satisfaction
      with program preparation for this specialty area; the role of the use of the
      curriculum with practice-partners to strengthen transfer of knowledge to the
      clinical environment; and the use of this curriculum interprofessionally.

PMID- 25771264
TI  - High expression of post-treatment Ki-67 status is a risk factor for locoregional
      recurrence following breast-conserving surgery after neoadjuvant chemotherapy.
AB  - INTRODUCTION: During the past decade, neoadjuvant chemotherapy (NAC) has been
      increasingly used in patients to reduce large tumors to a size eligible for
      breast-conserving therapy (BCT). However, the association between NAC and Ki-67
      has not yet been fully elucidated. The aim of this study was to evaluate the
      prognostic significance of Ki-67, specifically after NAC followed by BCT,
      particularly in terms of locoregional recurrence (LRR). METHODS: A total 217
      patients who received BCT after NAC were retrospectively analyzed. In these
      patients, immunohistochemistry analyses defined four tumor subtypes, Luminal A,
      Luminal B, Triple negative, and HER2 type. Ki-67 was examined by
      immunohistochemistry in both pretreatment core needle samples and post-treatment
      surgical excision specimens. High Ki-67 expression was defined as >20%. The
      prognostic factors LRR, locoregional relapse-free survival (LRRFS), and overall
      survival (OS) were analyzed. RESULTS: In total, LRR developed in 14 patients, and
      the 5 year-LRRFS was 94.2%. Post-treatment high Ki-67 expression, triple
      negative, the presence of lymphovascular invasion, and histological grade 3 were
      significantly high in LRR for prognostic factors (P < 0.05). There were
      significant differences in Kaplan-Meier method for LRRFS curves according to
      these three factors for patients receiving BCT following NAC (P < 0.05). There
      was a significant difference in the 5 year-OS for patients with and without LRR
      (41.7% vs. 93.9%, P < 0.001). CONCLUSION: Post-treatment high Ki-67 expression
      could be one of the important prognostic factors of LRR, and require careful
      follow-up on LRR at the time of surveillance.

PMID- 25771265
TI  - Aspects of abuse: abusive head trauma.
AB  - Abusive Head Trauma (AHT) is a form of child physical abuse that involves
      inflicted injury to the brain and its associated structures. Abusive Head Trauma,
      colloquially called Shaken Baby Syndrome, is the most common cause of serious or
      fatal brain injuries in children aged 2 years and younger. The American Academy
      of Pediatrics recommends the term Abusive Head Trauma, as opposed to Shaken Baby
      Syndrome, as the former term encompasses multiple forms of inflicted head injury
      (inertial, contact, and hypoxic-ischemic) and a range of clinical presentations
      and radiologic findings and their sequelae. Children diagnosed with AHT are 5
      times more likely to die compared with accidentally head-injured children, yet
      signs and symptoms are not always obvious, and therefore the diagnosis can be
      overlooked. Therefore, the American Academy of Pediatrics has tasked
      pediatricians with knowing how and when to begin an evaluation of children with
      signs and symptoms that could possibly be due to AHT. Overall, a detailed history
      of present illness and medical history, recognition of physical and radiological
      findings, and careful interpretation of retinal pathology are important aspects
      of formulating the differential diagnoses and increasing or decreasing the index
      of suspicion for AHT. 

PMID- 25771266
TI  - Aspects of abuse: recognizing and responding to child maltreatment.
AB  - Child maltreatment is a public health problem and toxic stress impacting at least
      1 in 8 children by the age of 18 years. Maltreatment can take the form of
      physical and sexual abuse, neglect, and emotional maltreatment. While some
      children may experience only one form of maltreatment, others may survive
      multiple forms, and in some cases particularly complex forms of maltreatment such
      as torture and medical child abuse. When considering maltreatment, providers
      should be adept at obtaining a thorough history not only from the parent but when
      appropriate also from the patient. The most common form of child maltreatment is
      neglect, which encompasses nutritional and medical neglect, as well as other
      forms such as physical and emotional neglect. Talking with caregivers about
      stressors and barriers to care may give insight into the etiology for neglect and
      is an opportunity for the provider to offer or refer for needed assistance.
      Familiarity with injury patterns and distribution in the context of developmental
      milestones and injury mechanisms is critical to the recognition of physical
      abuse. While most anogenital exam results of child victims of sexual abuse are
      normal, knowing the normal variations for the female genitalia, and thereby
      recognizing abnormal findings, is important not only forensically but also more
      importantly for patient care. Pattern recognition does not only apply to specific
      injuries or constellation of injuries but also applies to patterns of behavior.
      Harmful patterns of behavior include psychological maltreatment and medical child
      abuse, both of which cause significant harm to patients. As health professionals
      serving children and families, pediatric providers are in a unique position to
      identify suspected maltreatment and intervene through the health care system in
      order to manage the physical and psychological consequences of maltreatment and
      to promote the safety and well-being of children and youth by making referrals to
      child protective services. 

PMID- 25771268
TI  - Editorial 52.1.

PMID- 25771269
TI  - Improving patient safety in neurologic surgery.
AB  - The delivery of safe healthcare is one of the fundamental tenets of medicine, but
      the study of patient safety has lagged in neurosurgery. Patients are at high risk
      for medical errors, adverse events, and complications. To prevent and mitigate
      these risks, it is not enough to shame and blame individual practitioners for
      mistakes or errors. Complete health care delivery systems should be evaluated for
      ways to reduce adverse events and errors, and restrict the harm they cause. This
      article reviews the context of patient safety in history, and outlines the ways
      in which patient safety is being improved. 

PMID- 25771267
TI  - A Multipronged, Adaptive Approach for the Recruitment of Diverse Community
      Residing Elders with Memory Impairment: The MIND at Home Experience.
AB  - OBJECTIVE: To provide a critical review of a multipronged recruitment approach
      used to identify, recruit, and enroll a diverse community-based sample of persons
      with memory disorders into an 18-month randomized, controlled dementia care
      coordination trial. METHODS: Descriptive analysis of a recruitment approach
      comprised five strategies: community liaison ("gatekeepers") method, letters sent
      from trusted community organizations, display and distribution of study materials
      in the community, research registries, and general community outreach and
      engagement activities. Participants were 55 community organizations and 63 staff
      of community organizations in Baltimore, Maryland. Participant referral sources,
      eligibility, enrollment status, demographics, and loss to follow-up were tracked
      in a relational access database. RESULTS: In total, 1,275 referrals were received
      and 303 socioeconomically, cognitively, and racially diverse community-dwelling
      persons with cognitive disorders were enrolled. Most referrals came from letters
      sent from community organizations directly to clients on the study's behalf (39%)
      and referrals from community liaison organizations (29%). African American/black
      enrollees were most likely to come from community liaison organizations.
      CONCLUSION: A multipronged, adaptive approach led to the successful recruitment
      of diverse community-residing elders with memory impairment for an intervention
      trial. Key factors for success included using a range of evidence-supported
      outreach strategies, forming key strategic community partnerships, seeking
      regular stakeholder input through all research phases, and obtaining "buy-in"
      from community stakeholders by aligning study objectives with perceived unmet
      community needs.

PMID- 25771270
TI  - Errors in neurosurgery.
AB  - Medical errors are common and dangerous, estimated to cause over 400,000 deaths
      per year in the United States alone. The field of neurosurgery is not immune to
      these errors, and many studies have begun analyzing the frequency and types of
      errors that neurosurgical patients experience, along with their effects and
      causes. Fortunately, these data are guiding new innovations to reduce and prevent
      errors, like checklists, computerized order entry, and an increased appreciation
      for volume-outcome relationships. This article describes the epidemiology of
      errors, their classification, methods for identifying and discovering errors, and
      new strategies for error prevention. 

PMID- 25771271
TI  - Adverse events in neurosurgery and their relationship to quality improvement.
AB  - Adverse events are common in neurosurgery. Their reporting is inconsistent and
      widely variable due to nonuniform definitions, data collection mechanisms, and
      retrospective data collection. Historically, neurosurgery has lagged behind
      general and cardiac surgical fields in the creation of multi-institutional
      prospective databases allowing for benchmarking and accurate adverse
      event/outcomes measurement, the bedrock of evidence used to guide quality
      improvement initiatives. The National Neurosurgery Quality and Outcomes Database
      has begun to address this issue by collecting prospective, multi-institutional
      outcomes data in neurosurgical patients. Once reliable outcomes exist, various
      targeted quality improvement strategies may be used to reduce adverse events and
      improve outcomes. 

PMID- 25771272
TI  - The relationship between national health care policies and quality improvement in
      neurosurgery.
AB  - Although federal programs aimed at improving the overall value of health care are
      well intentioned, most remain fundamentally flawed in terms of their metrics,
      their methodologies, and the pace at which they are being implemented. Without a
      serious reevaluation of these strategies, these programs will, at best, have
      limited effectiveness, and, at worst, lead to critical deteriorations in patient
      quality, safety, and access to care. 

PMID- 25771273
TI  - Quality improvement tools and processes.
AB  - The Model for Improvement and the Plan-Do-Study-Act cycle is a popular quality
      improvement (QI) tool for health care providers to successfully lead QI projects
      and redesign care processes. This tool has several distinct components that must
      be addressed in sequence to organize and critically evaluate improvement
      activities. Unlike other health sciences clinical research, QI projects and
      research are based on dynamic hypotheses that develop into observable, serial
      tests of change with continuous collection and feedback of performance data to
      stakeholders. 

PMID- 25771274
TI  - Cost-effectiveness research in neurosurgery.
AB  - Cost and value are increasingly important components of health care discussions.
      Despite a plethora of cost and cost-effectiveness analyses in many areas of
      medicine, there has been little of this type of research for neurosurgical
      procedures. This scarcity is vexing because this specialty represents one of the
      most expensive areas in medicine. This article discusses the general principles
      of cost-effectiveness analyses and reviews the cost- and cost-effectiveness
      related research to date in neurosurgical subspecialties. The need for
      standardization of cost and cost-effectiveness measurement and reporting within
      neurosurgery is highlighted and a set of metrics for this purpose is defined. 

PMID- 25771275
TI  - Economics, innovation, and quality improvement in neurosurgery.
AB  - Innovation to improve patient care quality is a priority of the neurosurgical
      specialty since its beginnings. As the strain on health care resources increases,
      the cost of these quality improvements is becoming increasingly important. The
      aims of this article are to review the available tools for assessing the cost of
      quality improvement along with the willingness to pay and to provide a conceptual
      framework for the assessment of innovations in terms of quality and economic
      metrics and provide examples from the neurosurgical literature. 

PMID- 25771276
TI  - Volume-outcome relationships in neurosurgery.
AB  - For a variety of neurosurgical conditions, increasing surgeon and hospital
      volumes correlate with improved outcomes, such as mortality, complication rates,
      length of stay, hospital charges, and discharge disposition. Neurosurgeons can
      improve patient outcomes at the population level by changing practice and
      referral patterns to regionalize care for select conditions at high-volume
      specialty treatment centers. Individual practitioners should be aware of where
      they fall on the volume spectrum and understand the implications of their
      practice and referral habits on their patients. 

PMID- 25771277
TI  - Neurosurgical checklists: a growing need.
AB  - The US health care system is currently undergoing a paradigm shift from pay-for
      service toward pay-for-performance reimbursement, with a focus on quality
      measures and patient satisfaction. An important tool gaining increasing emphasis
      during the quality revolution is the surgical checklist. What was once perceived
      as an invasion of the practitioner's integrity is now a mainstay in all operating
      rooms, mandated by several national organizations. Although other fields have
      pioneered the checklist revolution, neurosurgery is now beginning to follow suit.
      The authors review the available published neurosurgical checklists and their
      early results on patient safety. 

PMID- 25771278
TI  - Quality improvement in neurological surgery graduate medical education.
AB  - There has been no formal, standardized curriculum for neurosurgical resident
      education in quality improvement. There are at least 2 reasons to integrate a
      formalized quality improvement curriculum into resident education: (1) increased
      emphasis on the relative quality and value (cost-effectiveness) of health care
      provided by individual physicians, and (2) quality improvement principles empower
      broader lifelong learning. An integrated quality improvement curriculum should
      comprise specific goals and milestones at each level of residency training. This
      article discusses the role and possible implementation of a national program for
      quality improvement in neurosurgical resident education. 

PMID- 25771279
TI  - Technology and simulation to improve patient safety.
AB  - Improving the quality and efficiency of surgical techniques, reducing technical
      errors in the operating suite, and ultimately improving patient safety and
      outcomes through education are common goals in all surgical specialties. Current
      surgical simulation programs represent an effort to enhance and optimize the
      training experience, to overcome the training limitations of a mandated 80-hour
      work week, and have the overall goal of providing a well-balanced resident
      education in a society with a decreasing level of tolerance for medical errors. 

PMID- 25771280
TI  - Electronic medical records and quality improvement.
AB  - Widespread adoption of electronic medical records (EMRs) in the United States is
      transforming the practice of medicine from a paper-based cottage industry into an
      integrated health care delivery system. Most physicians and institutions view the
      widespread use of EMRs to be inevitable. But the transformation has not been
      painless. Many have questioned whether the substantial investment in electronic
      health records has really been justified by improved patient outcomes or quality
      of care. This article describes historical and recent efforts to use EMRs to
      improve the quality of patient care, and provides a roadmap of EMR uses for the
      foreseeable future. 

PMID- 25771281
TI  - Using clinical registries to improve the quality of neurosurgical care.
AB  - Despite rising and unsustainable US health care costs, many stakeholders feel
      that the quality of medical services is limited and inconsistent. Value-based
      reforms are touted as the key to achieving health care system sustainability.
      Health care value is defined as quality delivered divided by cost incurred.
      Unfortunately, quality in health care is difficult to accurately define and
      methods to reliably assess and report health care quality are often lacking.
      Clinical registries have emerged as important mechanisms to define, measure, and
      promote health care quality. The purpose of this article is to describe the role
      of registries in neurosurgical quality improvement. 

PMID- 25771282
TI  - Measuring outcomes for neurosurgical procedures.
AB  - Health care evolution has led to focused attention on clinical outcomes of care.
      Surgical disciplines are increasingly asked to provide evidence of treatment
      efficacy. As the technological advances push the surgical envelope further, it
      becomes imperative that postoperative outcomes are studied in a prospective
      fashion to assess the quality of care provided. The authors present their
      experience from a multiyear implementation of an outcomes initiative and share
      lessons learned, emphasizing the important structural elements of such an
      endeavor. 

PMID- 25771283
TI  - Development and implementation of guidelines in neurosurgery.
AB  - Although it is intuitive that any neurosurgeon would seek to consistently apply
      the best available evidence to patient management, the application of evidence
      based medicine (EBM) principles and clinical practice guidelines (CPGs) remains
      variable. This article reviews the origin and process of EBM, and the
      development, assessment, and applicability of EBM and CPGs in neurosurgical care,
      aiming to demonstrate that CPGs are one of the valid available options that exist
      to improve quality of care. CPGs are not intended to define the standard of care
      but to compile dynamic advisory statements, which need to be updated as new
      evidence emerges. 

PMID- 25771284
TI  - The role of neurosurgery journals in evidence-based neurosurgical care.
AB  - Neurosurgery journals have played an active role in improving the quality of the
      neurosurgical literature. This role has expanded to improve the quality of care
      by incorporating an evidence-based view of neurosurgery practice. Neurosurgery
      journals have facilitated the organization of knowledge into clinically useful
      forms via the publication of meta-analyses and dissemination of clinical practice
      guidelines. Peer review continues to be a core feature of neurosurgery
      publishing, with attendant ethical and procedural safeguards. Finally,
      neurosurgery journals have spearheaded innovative responses to cultural and
      technological changes, including initiatives to deliver high-quality research in
      electronic formats and support the education of future neurosurgery
      investigators. 

PMID- 25771285
TI  - Comanagement hospitalist services for neurosurgery.
AB  - Neurosurgeons and hospitalists are turning to comanagement arrangements to
      address medical problems in surgical patients. Compared with traditional medical
      consultation, comanagement lets the hospitalist share authority and
      responsibility for patient care. It is associated with improved provider
      satisfaction and more efficient care, but impact on clinical outcomes is
      uncertain. Shared responsibility for patient care requires careful planning to
      avoid conflicts and fragmentation of care. 

PMID- 25771286
TI  - Recent advances in the patient safety and quality initiatives movement:
      implications for neurosurgery.
AB  - The US health care system is fragmented in terms of quality care, costs, and
      patient satisfaction. With the passage of the Affordable Care Act, national
      attention has been placed on the health care system, but effective change has yet
      to be observed. Unnecessary costs, medical errors, and uncoordinated efforts
      contribute to patient morbidity, mortality, and decreased patient satisfaction.
      In addition to national efforts, local initiatives within individual departments
      must be implemented to improve overall satisfaction without the sacrifice of
      costs. In this article, the current issues with the health care system and
      potential initiatives for neurosurgery are reviewed. 

PMID- 25771287
TI  - Quality improvement in neurosurgery.

PMID- 25771289
TI  - Assessment and modelling of Ni(II) retention by an ion-imprinted polymer:
      application in natural samples.
AB  - Three novel Ni(II)-Ion-Imprinted Polymer (IIP) were synthesized by precipitation
      polymerization of ethylene glycol dimethacrylate (crosslinker) with a complex of
      nickel(II) and vinylbenzyl iminodiacetic acid (VbIDA). The three IIPs were
      prepared with various mixtures of porogen solvents: methanol, methanol/2
      methoxyethanol and methanol/acetonitrile (IIP1, IIP2 and IIP3, respectively). Non
      Imprinted Polymers (NIP1, NIP2 and NIP3) were prepared as control polymers in
      similar conditions but with pure VbIDA instead of VbIDA-Ni. These polymers were
      characterized by FTIR, BET, SEM and tested for their efficiency and selectivity
      in Ni(II) retention. The most efficient (IIP1, around 12 mg g(-1) of nickel) was
      then positively checked for Ni(II) retention in presence of some competing
      species over a wide range of concentration. Finally Ni(II) retention by IIP1 was
      successfully demonstrated in natural samples. The modelling of the different
      experiments (Langmuir, Freundlich but also PROSECE and WHAM VII, frequently used
      in environmental studies) allowed demonstrating the presence of completely
      different binding sites when considering the ion-imprinted polymer and the non
      imprinted one, and therefore led to a better understanding of what the imprinting
      effect is.

PMID- 25771288
TI  - Cardiovascular correlates of platelet count and volume in the Framingham Heart
      Study.
AB  - PURPOSE: Platelet count and volume are inexpensive, routinely assayed biomarkers
      associated with cardiovascular health, but specific relationships among platelet
      indices, cardiovascular risk factors, and disease warrant further investigation.
      The purpose of this study was to understand associations among platelet count,
      volume, and 20 cardiovascular health-related variables in the Framingham Heart
      Study (FHS). METHODS: Cross-sectional analyses were performed on platelet count
      and volume associations with cardiovascular health indicators in three FHS
      cohorts (original n = 964, offspring n = 2699, and third generation n = 2419)
      using multivariate linear regression analysis. Time-to-event analysis was used
      for cardiovascular disease-related event incidences using Kaplan-Meier plots and
      Cox proportional hazards regression adjusted for age and sex. RESULTS: Results
      were concordant with the hypothesis that higher platelet counts are associated
      with less favorable cardiovascular risk profiles, although mean platelet volume
      associations were weaker. In our analysis, increased platelet count across FHS
      cohorts was consistently associated with smoking, triglycerides, low-density
      lipoprotein, and total cholesterol levels. Some associations with platelet count
      appeared sex dependent. CONCLUSIONS: Significant associations of common blood
      platelet measurements are observed with sex and cardiovascular risk factors,
      namely smoking and lipids. Research is warranted to confirm these relationships
      in other cohorts, evaluate differences by ethnicity, and examine longitudinal
      effects on disease risk.

PMID- 25771290
TI  - Superhydrophobicity: cavity growth and wetting transition.
AB  - We show by using AFM colloidal probe microscopy (combinations of
      hydrophobic/superhydrophobic as probe/surface) that superhydrophobicity displays
      a set of specific events when compared with hydrophobicity. Both attraction (due
      to capillary and wetting forces) and repulsion (most likely due to repelling
      air/vapor layers or micro-/nanobubbles) occur upon approach and when surfaces are
      pulled apart both shorter range (50-100 nm or more) and longer range (several
      micrometers) attractive forces are displayed. The interaction is explained by
      forces generated through the formation of air and water vapor cavities, in the
      shorter-range (>50 nm) case maintaining a constant volume of the cavity, in
      agreement with calculation of capillary forces, and in the longer-range (>1 MUm)
      case through access of air to the cavity, in agreement with thermodynamics of
      cavity growth. An added sodium dodecyl sulphate surfactant gave a partially
      reversible wetting transition and reduced the longer-range interaction to shorter
      range, suggesting a transfer from the Cassie-Baxter to the Wenzel wetting regime.
      The findings would be of interest in development of practical applications, such
      as for anti-soiling, anti-icing, protection of electrical components and for
      extreme water-repellency in paper and textiles.

PMID- 25771291
TI  - Effect of electrostatic interactions on rejection of capsular and spherical
      particles from porous membranes: theory and experiment.
AB  - HYPOTHESES: Particle rejection from porous membranes will increase when particle
      and membrane carry like charges. The influence of charge on particle rejection
      can be modeled by first solving the Poisson-Boltzmann equation for the
      electrostatic particle-pore wall interaction energy, enabling one to predict the
      cross sectional particle concentration in a pore. Rejection coefficients can then
      be predicted by combining the Boltzmann factor with a hydrodynamic lag
      coefficient. EXPERIMENTS: Rejection experiments were conducted with three
      different spherical colloidal silica particles, a spherical virus (PRD1) and gold
      nanorods of two different aspect ratios (ratio of length to diameter). Track
      etched polycarbonate microfiltration and ultrafiltration membranes having nearly
      parallel pores of cylindrical cross-section were used. Experiments were conducted
      under conditions where both particle and membrane carried a negative charge as
      well as under conditions where surface charges had minimal impact. Experiments
      were designed to cover a broad range of dimensionless particle sizes under
      conditions when convection dominated particle transport. FINDINGS: Model
      predictions and experimental measurements demonstrate that particle rejection can
      be enhanced significantly when particle and pore carry like charges.

PMID- 25771292
TI  - In reference to "The value of resident presentations at scientific meetings".

PMID- 25771293
TI  - Towards standardisation and improved understanding of sleep restriction therapy
      for insomnia disorder: A systematic examination of CBT-I trial content.
AB  - Sleep restriction therapy is a core element of contemporary cognitive-behavioural
      therapy for insomnia and is also effective as a single-component therapeutic
      strategy. Since its original description, sleep restriction therapy has been
      applied in several different ways, potentially limiting understanding of key
      therapeutic ingredients, mode of action, evidence synthesis, and clinical
      implementation. We sought to examine the quality of reporting and variability in
      the application of sleep restriction therapy within the context of insomnia
      intervention trials. Systematic literature searches revealed 88 trials of
      cognitive-behavioural therapy/sleep restriction therapy that met pre-defined
      inclusion/exclusion criteria. All papers were coded in relation to their
      description of sleep restriction therapy procedures. Findings indicate that a
      large proportion of papers (39%) do not report any details regarding sleep
      restriction therapy parameters and, for those papers that do, variability in
      implementation is present at every level (sleep window generation, minimum time
      in-bed, sleep efficiency titration criteria, and positioning of sleep window).
      Only 7% of papers reported all parameters of sleep restriction treatment. Poor
      reporting and variability in the application of sleep restriction therapy may
      hinder progress in relation to evidence synthesis, specification of mechanistic
      components, and refinement of therapeutic procedures for patient benefit. We set
      out guidelines for the reporting of sleep restriction therapy as well as a
      research agenda aimed at advancing understanding of sleep restriction therapy. 

PMID- 25771294
TI  - Efficacy of sleep position modification to treat positional obstructive sleep
      apnea.
AB  - OBJECTIVE/BACKGROUND: To assess the feasibility and efficacy of sleep position
      modification in preventing supine sleep and improving sleep-disordered breathing
      and relevant clinical outcomes in positional obstructive sleep apnea (OSA)
      patients. PATIENTS/METHODS: Eighty-six consecutive participants with moderate
      positional OSA on routine diagnostic polysomnography underwent a randomized
      controlled parallel group design trial of 4-weeks treatment using a sleep
      position modification device (active) or sleep hygiene advice (control). Outcomes
      were measured at baseline and following a 4-week treatment period. RESULTS: There
      was a significant reduction in the amount of supine sleep in the active group
      (mean +/- SD change from baseline, active group 99.5 +/- 85.2 minutes, control
      group 68.6 +/- 103.2 minutes, p = 0.002), and an improvement in apnea-hypopnea
      index (AHI) (active group reduced by 9.9 +/- 11.6, control group reduced by 5.3
      +/- 13.9, p = 0.013). Post-hoc analyses indicated that positional therapy was
      most effective for patients with baseline AHI cut-off above 20 (p = 0.02).
      Logistic regression showed that a treatment response (AHI < 10) was more likely
      in the active group (OR = 5.57), and those with higher baseline nadir oxygen
      desaturation (OR = 1.95) and non-supine AHI (OR = 0.55). There were no
      significant improvements in quality of life, daytime sleepiness, mood, symptoms,
      neuropsychological measures or blood pressure in the active group. CONCLUSIONS:
      The position device utilized in this study was effective in reducing supine sleep
      and AHI, which was significant in those with baseline AHI >=20. Longer duration
      studies of physical treatments that modify sleep position are needed to explore
      further whether additional clinical benefits in are achievable.

PMID- 25771295
TI  - Classification of a Proteus penneri clinical isolate with a unique O-antigen
      structure to a new Proteus serogroup, O80.
AB  - Proteus penneri is an opportunistic pathogen, which may cause severe diseases,
      most frequently urinary tract infections in immunocompromised patients. P.
      penneri Br 114 exhibiting a good swarming growth ability as an S-form strain was
      isolated from a wound of a patient in Lodz, Poland. Serological studies using
      ELISA and Western blotting and chemical analyses along with (1)H and (13)C NMR
      spectroscopy showed that the O-antigen (O-polysaccharide) of this strain is
      unique among the known Proteus serotypes O1-O79. It possesses a linear
      pentasaccharide repeating unit containing a partially O-acetylated amide of D
      glucuronic acid (GlcA) with L-serine having the following structure: [structure:
      see text]. These data are a basis for creating a new Proteus serogroup, O80, so
      far represented by the single Br 114 isolate. The O80 is the 21st O-serogroup
      containing P. penneri strains and the fourth serogroup based on Proteus spp.
      clinical isolates from Lodz, Poland.

PMID- 25771296
TI  - Mechanochemical click reaction as a tool for making carbohydrate-based triazole
      linked self-assembling materials (CTSAMs).
AB  - Various glycosides in which glycosylated triazole residues are anchored on to a
      central phenyl ring have been prepared under green reaction conditions by a
      solvent-free mechanochemical method. Some of the glycosides exhibited the ability
      to form gels when in contact with long chain hydrocarbons, e.g. hexane, heptane
      and octane, and this property was phase-selective. Thus, from a mixture of hexane
      water, the compounds preferably absorbed the alkane to form a gel. The gelation
      ability was found to increase with an increasing number of substituents on the
      phenyl ring but only up to tetra-substitution. The hexa-substituted phenyl
      derivative did not swell in the hydrocarbon solvents investigated. The
      spontaneous self-assembling properties of these compounds in hexane have been
      investigated by transmission electron microscopy (TEM). Molecular modelling was
      used to optimize the structural geometry of these carbohydrate-based triazole
      linked self-assembling materials (CTSAMs) and to rationalize their behaviour. 

PMID- 25771298
TI  - Novel fabrication of a 2D ring array for real-time volumetric endoscopic
      ultrasound imaging.
AB  - The work presents the development of a forward-looking 2D ring array for real
      time volumetric endoscopic ultrasonic imaging using a novel rotary-dicing method.
      The completed array has an inner diameter of 3.5 mm, outer diameter of 5 mm, and
      50 equal-area elements distributed concentrically. With a single front matching
      layer and a light backing, the array shows a center frequency of 3.5 MHz, a
      fractional bandwidth of 48%, insertion loss of -21.6 dB and cross-talk between
      nearest neighbor elements of 35.3 dB. The beam profile, two-dimensional pulse
      echo point spread response, and phantom imaging of the array were studied with
      the Field-II simulation package. These promising results suggest that the rotary
      dicing technology is an effective way to fabricate 2D ring array.

PMID- 25771297
TI  - C-glycosphingolipid precursors via iodocyclization of homoallyic
      trichloroacetimidates.
AB  - The iodocyclization of homoallylic trichloroacetimidates derived from alpha-C
      allyl galactoside were investigated. In line with the stereochemical trend
      observed for less substituted non-glycosylated frameworks, E and Z substrates
      delivered stereoselectively the 1,3-anti and 1,3-syn amino alcohol motifs,
      respectively. These products are advanced precursors to C-glycosides of the
      potent immunostimulatory glycolipid KRN7000. 

PMID- 25771299
TI  - Ultrasonic characterization of GRC with high percentage of fly ash substitution.
AB  - New applications of non-destructive techniques (NDT) with ultrasonic tests
      (attenuation and velocity by means of ultrasonic frequency sweeps) have been
      developed for the characterization of fibre-reinforced cementitious composites.
      According to new lines of research on glass-fibre reinforced cement (GRC) matrix
      modification, two similar GRC composites with high percentages of fly ash and
      different water/binder ratios will be studied. Conventional techniques have been
      used to confirm their low Ca(OH)(2) content (thermogravimetry), fibre integrity
      (Scanning Electron Microscopy), low porosity (Mercury Intrusion Porosimetry) and
      good mechanical properties (compression and four points bending test). Ultrasound
      frequency sweeps allowed the estimation of the attenuation and pulse velocity as
      functions of frequency. This ultrasonic characterization was correlated
      successfully with conventional techniques.

PMID- 25771300
TI  - A novel amperometric biosensor based on gold nanoparticles anchored on reduced
      graphene oxide for sensitive detection of l-lactate tumor biomarker.
AB  - In this work, a novel amperometric biosensor based on gold nanoparticles anchored
      on reduced graphene oxide (RGO-AuNPs) and l-lactate dehydrogenase (LDH) was
      developed for the sensing of l-lactate. Firstly, the RGO-AuNPs modified screen
      printed electrodes were tested for NADH detection showing a wide dynamic range
      and a low detection limit. Next, the biosensor was constructed by incorporating
      both enzyme and RGO-AuNPs in a sol gel matrix derived from tetrametoxysilane and
      methyltrimetoxysilane. The enzyme loading, working pH, and coenzyme concentration
      were optimized. The biosensor linearly responded to l-lactate in the range of
      10uM-5mM and showed a good specific sensitivity of 154uA/mMcm(2) with a detection
      limit of 0.13uM. This was accompanied by good reproducibility and operational
      stability. Tests on artificial serum proved that l-lactate can be determined
      practically without interferences from commonly interfering compounds such as
      urate, paracetamol and l-ascorbate. Our LDH/RGO-AuNPs/SPCE based biosensor thus
      performs as electrochemical device for the detection of l-lactate as a viable
      early cancer bio-marker. 

PMID- 25771301
TI  - Nanogold bioconjugates for direct and sensitive multiplexed immunosensing.
AB  - The use of nanogold bioconjugates for direct detection of the antibody-antigen
      immunoreaction is addressed. The integration of gold nanoparticles tracers as
      signal generators in microarray immunosensing and compact disc detection
      technique show important advantages to reach sensitive, selective, high
      throughput, reliable and cost-effective assays. For that, a thorough study of the
      performances of the size of spherical nanogold particles and coating density was
      developed. The size of the nanoparticle determines the optimal antibody dilution,
      being the smaller particles the best performing ones. Enhancement effect of lower
      size is also studied. The gold labeling method do not affects the recognition
      capability of the labeled proteins. As a proof of concept, the nanoconjugates
      were used for the simultaneous and direct determination of small molecules.
      Employing nanogold bioconjugates as recognition labels resulted in robust and
      reliable assays, reaching a sensitivity of 0.03 and 1.3MUg/L for sulfasalazine
      and atrazine, respectively. This shows that the use of nanogold bioconjugates for
      direct immunosensing is very competitive, achieving highly sensitive and
      reproducible assays (RSD<10%). This approach would simultaneously determine both
      small and large molecular size targets, in different formats, using the same
      detection mode what paves the way for many other applications in different
      scenarios. 

PMID- 25771302
TI  - Single-cell PCR of genomic DNA enabled by automated single-cell printing for cell
      isolation.
AB  - Single-cell analysis has developed into a key topic in cell biology with future
      applications in personalized medicine, tumor identification as well as tumor
      discovery (Editorial, 2013). Here we employ inkjet-like printing to isolate
      individual living single human B cells (Raji cell line) and load them directly
      into standard PCR tubes. Single cells are optically detected in the nozzle of the
      microfluidic piezoelectric dispenser chip to ensure printing of droplets with
      single cells only. The printing process has been characterized by using
      microbeads (10um diameter) resulting in a single bead delivery in 27 out of 28
      cases and relative positional precision of +/-350um at a printing distance of 6mm
      between nozzle and tube lid. Process-integrated optical imaging enabled to
      identify the printing failure as void droplet and to exclude it from downstream
      processing. PCR of truly single-cell DNA was performed without pre-amplification
      directly from single Raji cells with 33% success rate (N=197) and Cq values of
      36.3+/-2.5. Additionally single cell whole genome amplification (WGA) was
      employed to pre-amplify the single-cell DNA by a factor of >1000. This
      facilitated subsequent PCR for the same gene yielding a success rate of 64%
      (N=33) which will allow more sophisticated downstream analysis like sequencing,
      electrophoresis or multiplexing. 

PMID- 25771303
TI  - Disposable lateral flow-through strip for smartphone-camera to quantitatively
      detect alkaline phosphatase activity in milk.
AB  - A disposable lateral flow-through strip was developed for smartphone to fast one
      step quantitatively detect alkaline phosphatase (ALP) activity in raw milk. The
      strip comprises two functional components, a conjugation pad loaded with
      phosphotyrosine-coated gold nanoparticles (AuNPs@Cys-Try-p) and a testing line
      coated with anti-phosphotryosine antibody (anti-Tyr-p mAb). The dephosphorylation
      activity of ALP at the testing zone can be quantitatively assayed by monitoring
      the accumulated AuNPs-induced color changes by smartphone camera, thus providing
      a highly convenient portable detection method. A trace amount of ALP as low as
      0.1UL(-1) with a linear dynamic range of 0.1-150UL(-1) (R(2)=0.999) in
      pasteurized milk and raw milk can be one-step detected by the developed flow
      through strip within 10min, demonstrating the potential of smartphone-based
      portable sensing device for pathogen detection. This bio-hazards free lateral
      flow-through testing strip can be also used to fabricate rapid, sensitive and
      inexpensive enzyme or immunosensors for broad portable clinic diagnosis and food
      contamination analysis, particularly in point-of-care and daily food quality
      inspection. 

PMID- 25771304
TI  - Highly sensitive and doubly orientated selective molecularly imprinted
      electrochemical sensor for Cu(2.).
AB  - Studies on molecularly imprinted electrochemical sensors for metal ions
      determination have been widely reported. However, the sensitivity and selectivity
      of the sensors needs to be improved urgently. In the current work, a novel
      molecularly imprinted electrochemical sensor was originally developed for
      selective determination of ultratrace Cu(2+) by combining the metal-ligand
      chelate orientated recognition with enzyme amplification effect. The detection
      relied on a competition reaction between Cu(2+)-glycine (Cu-Gly) and horse radish
      peroxidase (HRP)-labeled Cu-Gly on the imprinted polymer membrane modified
      electrode. The sensitivity of this sensor was promoted by enzyme amplification.
      Selectivity was improved by the double-specificity derived from ligand-to-metal
      ion and metal-ligand chelate orientated recognition of 3D imprinted cavities.
      This technique was quantitatively sensitive to Cu(2+) concentrations ranging from
      0.5nmol/L to 30nmol/L, with a detection limit of 42.4pmol/L. which was lower than
      those in most of the reported methods. The allowable amounts of interference ions
      were higher when it compared to other common molecularly imprinted sensors.
      Moreover, the results of assaying several real samples have proven its
      feasibility for practical applications. 

PMID- 25771306
TI  - Diabetes and medical expenditures among non-institutionalized U.S. adults.
AB  - AIMS: This research presents a comprehensive picture of medical spending
      associated with diabetes in the United States, accounting for important
      population characteristics. METHODS: The Household Component (HC) of the 2010
      Medical Expenditure Panel Survey (MEPS) was used for this study. Regression
      analysis was used to compare medical spending between individuals with and
      without diabetes. The dependent variables of interest were total and out-of
      pocket expenditures related to medical care, hospital use, physician office
      visits, and prescription drug use. RESULTS: This study reveals that individuals
      with diabetes experience significantly greater medical, hospital, physician
      office, and prescription drug expenditures compared to those without diabetes.
      Even after controlling for predisposing, enabling, and need factors, adults with
      diabetes spent $1843 more on total medical expenditures and $353 more on out-of
      pocket medical expenditures than those without diabetes. Significant disparities
      were found in total and out-of-pocket expenditures by age, gender, education,
      race/ethnicity, and insurance status. CONCLUSIONS: Comprehensive interventions
      that focus on education and prevention should target individuals and communities
      at high-risk for diabetes and its complications. Our findings suggest that
      programs should focus on older Americans and those with poor health and mental
      health status.

PMID- 25771305
TI  - Decreased expression of ABAT and STC2 hallmarks ER-positive inflammatory breast
      cancer and endocrine therapy resistance in advanced disease.
AB  - BACKGROUND: Patients with Estrogen Receptor alpha-positive (ER+) Inflammatory
      Breast Cancer (IBC) are less responsive to endocrine therapy compared with ER+
      non-IBC (nIBC) patients. The study of ER+ IBC samples might reveal biomarkers for
      endocrine resistant breast cancer. MATERIALS & METHODS: Gene expression profiles
      of ER+ samples from 201 patients were explored for genes that discriminated
      between IBC and nIBC. Classifier genes were applied onto clinically annotated
      expression data from 947 patients with ER+ breast cancer and validated with RT
      qPCR for 231 patients treated with first-line tamoxifen. Relationships with
      metastasis-free survival (MFS) and progression-free survival (PFS) following
      adjuvant and first-line endocrine treatment, respectively, were investigated
      using Cox regression analysis. RESULTS: A metagene of six genes including the
      genes encoding for 4-aminobutyrate aminotransferase (ABAT) and Stanniocalcin-2
      (STC2) were identified to distinguish 22 ER+ IBC from 43 ER+ nIBC patients and
      remained discriminatory in an independent series of 136 patients. The metagene
      and two genes were not prognostic in 517 (neo)adjuvant untreated lymph node
      negative ER+ nIBC breast cancer patients. Only ABAT was related to outcome in 250
      patients treated with adjuvant tamoxifen. Three independent series of in total
      411 patients with advanced disease showed increased metagene scores and decreased
      expression of ABAT and STC2 to be correlated with poor first-line endocrine
      therapy outcome. The biomarkers remained predictive for first-line tamoxifen
      treatment outcome in multivariate analysis including traditional factors or
      published signatures. In an exploratory analysis, ABAT and STC2 protein
      expression levels had no relation with PFS after first-line tamoxifen.
      CONCLUSIONS: This study utilized ER+ IBC to identify a metagene including ABAT
      and STC2 as predictive biomarkers for endocrine therapy resistance.

PMID- 25771307
TI  - Single nucleotide polymorphisms in type 2 diabetes among Hispanic adults.
AB  - In this pilot study, we explore the genetic variation that may relate to type 2
      diabetes (T2D) among Hispanic adults. The genotypes of 36 Hispanic adults were
      analyzed by using the Cardio-Metabochip. The goal is to identify single
      nucleotide polymorphisms (SNPs) associated to T2D among Hispanic adults. A total
      of 26 SNPs were identified to be associated with T2D among Hispanic adults. None
      of these SNPs have been reported for T2D. By using the principle components
      analysis to analyze the genotype of 26 SNPs in 36 samples, the samples obtained
      from diabetic patients could be distinguished from the control samples. The
      findings support genetic involvement in T2D among Hispanic adults. 

PMID- 25771308
TI  - Modeling of in hospital mortality determinants in myocardial infarction patients,
      with and without type 2 diabetes, undergoing pharmaco-invasive strategy: the
      first national report using two approaches in Iran.
AB  - This study was conducted to compare the characteristics of patients, with and
      without diabetes mellitus, presenting with myocardial infarction (MI) and treated
      with coronary artery bypass grafting (CABG), percutaneous coronary intervention
      (PCI), or thrombolytic therapy. Factors related to mortality due to MI in Iran
      were also determined. This study was a prospective analysis. To analyze the data,
      Stata software (chi square, t test, Cox and logistic regression) was used.
      Participants were patients hospitalized for MI for the first time in 540
      hospitals from April, 2012 to March, 2013. Out of 20,750 patients with MI, 461 2
      (22.3%) had type 2 diabetes. MI case fatality rate was 13.22% (95%CI: 12.24
      14.19) and 11.78% (95%CI: 11.28-12.27) in patients with and without diabetes,
      respectively. The rates of CABG, PCI, and thrombolytic therapy use were 4.2%, 8%,
      and 58% in patients with diabetes, and 2.1%, 6.5%, and 55% in patients without
      diabetes. The odds ratio of mortality for ST segment elevation myocardial
      infarction (STEMI) and chest pain resistant to treatment was, respectively, 6.3
      and 2.8 in those with diabetes, and 3.9 and 3.7 in patients without diabetes. The
      hazard ratio of mortality for gender, education, smoking, left bundle branch
      block, PCI, and type of MI was different between the two groups (P<0.05).
      Characteristics of patients dying post MI were different in those with or without
      diabetes mellitus. Although use of CABG, PCI, and thrombolytic therapy was more
      frequent in patients with diabetes than without, mortality was higher in diabetes
      patients. 

PMID- 25771309
TI  - Metformin utilisation in Australian community and aged care settings.
AB  - OBJECTIVE: The objective of this study was to: (i) evaluate the potentially
      inappropriate prescribing (PIP; defined as the use of metformin in the presence
      of contraindications and/or use in excessive dosage based on the renal function)
      of metformin in people receiving medication reviews in Australia and (ii)
      identify the predictors for PIP of metformin. METHOD: Retrospective study of
      patients taking metformin through a large medication review database, containing
      records between January 2010 and June 2012. Data, including demographics, medical
      conditions, medications and relevant pathology results, were extracted for
      analysis. Multivariate logistic regression analysis was used to detect risk
      factors for PIP of metformin. RESULTS: Medication reviews pertaining to 6386
      patients who received Home Medicines Reviews (HMRs, n=5327) or Residential
      Medication Management Reviews (RMMRs, n=1059) were included in this study.
      Overall, there were 12.9% (n=685) of patients in the HMR group and 17.4% (n=184)
      of patients in the RMMR group who had PIP of metformin. Multivariate logistic
      regression showed age, gender and type of medication review service as the
      significant (p<0.05) independent risk factors for PIP of metformin. CONCLUSION:
      Metformin was often used in patients with contraindications, or in higher than
      recommended dosages in patients with renal impairment. Given the recent debate in
      the literature about the role of metformin in the presence of contraindications,
      a detailed prospective study in patients with contraindications and its
      association with lactic acidosis is warranted to establish the way in which
      metformin is to be used in these patients.

PMID- 25771312
TI  - Compost quality: is research still needed to assess it or do we have enough
      knowledge?

PMID- 25771310
TI  - Disease modifying therapies in type 1 diabetes: Where have we been, and where are
      we going?
AB  - With more than four decades of clinical research and 25 years of clinical trials,
      much is known about the natural history of T1D before and after clinical
      diagnosis. We know that autoimmunity occurs early in life, that islet
      autoimmunity inevitably leads to clinically overt disease, and that some immune
      therapies can alter the disease course. In the future, we will likely conduct
      trials to more deeply explore mechanisms of disease and response to therapy,
      employ combinations of agents including those aimed at supporting beta cells,
      consider the use of chronic, intermittent therapy, focus studies on preventing
      progression from islet autoimmunity, and consider the potential benefits of
      studying children independently from adults. Much of this work will depend upon
      clinical trial networks such as Diabetes TrialNet. Such networks not only have
      the expertise to conduct studies but their sharing of data and samples also
      allows for discovery work by multiple investigators, laying the groundwork for
      the future. Working with patients, families, funders and industry, such
      collaborative networks can accelerate the translation of science to clinical
      practice to improve the lives of those living with T1D. 

PMID- 25771313
TI  - The current trends for lateral unicondylar knee arthroplasty.
AB  - Unicompartmental osteoarthritis of the knee is a relatively common disease that
      is seen in 40% of the population. Although disease isolated to the medial
      compartment of the knee is more common, isolated lateral disease also frequently
      exists (25% vs 10%). However, surgeons perform medial unicondylar knee
      replacement at a ratio of 10:1 when compared with lateral unicondylar knee
      replacement. This may be attributed to lack of familiarity or the increased
      difficulty of the procedure. Recent literature suggests that with proper patient
      selection, surgical technique, and implant choice, early survivorship ranges from
      95% to 99%. 

PMID- 25771314
TI  - Modes of failure in metal-on-metal total hip arthroplasty.
AB  - Use of large-head metal-on-metal (MoM) bearing surfaces in total hip arthroplasty
      (THA) has created new and unique modes of failure for this type of articulation.
      These unique modes are in addition to the traditional modes of failure seen in
      conventional THA, which include instability, osteolysis, infection, iliopsoas
      tendinitis, aseptic loosening, and periprosthetic fracture. Ion levels and cross
      sectional imaging are helpful when evaluating a MoM patient in the identification
      of adverse local tissue reactions. Unique modes of failure in MoM THA include
      tissue necrosis, metallosis-induced osteolysis, skin hypersensitivity reactions,
      and rarely systemic cobaltism. This article outlines the evaluation and treatment
      of modes of failure in MoM THA. 

PMID- 25771315
TI  - Total hip arthroplasty after previous fracture surgery.
AB  - Total hip arthroplasty can be a very effective salvage treatment for both failed
      fracture surgery and hip arthritis that may occur after prior fracture surgery.
      The rate of complications is significantly increased including especially
      infection, dislocation, and loosening. Complications are more likely to occur
      after failed open reduction and internal fixation than after posttraumatic
      arthritis. Adequately ruling out infection before hip arthroplasty can be
      difficult. The best predictor of infection is a prior infection. Long-term
      outcomes can be comparable to outcomes in other conditions if complications are
      avoided.

PMID- 25771316
TI  - A growing problem: acetabular fractures in the elderly and the combined hip
      procedure.
AB  - Acetabular fractures in the elderly are most frequently the result of low-energy
      trauma and present unique management challenges to orthopedic surgeons.
      Evaluation and treatment should be performed in a multidisciplinary fashion with
      early involvement of internal medicine subspecialists and geriatricians. Distinct
      fracture patterns and pre-existing osteoarthritis and osteoporosis necessitate
      careful preoperative planning. The role of total hip arthroplasty should also be
      considered when surgical treatment is indicated. The outcomes of acetabular
      fractures in the elderly have improved, but complications remain higher and
      results less satisfactory than in younger individuals. The lack of randomized
      controlled trials has limited the ability to establish an evidence-based
      treatment algorithm. 

PMID- 25771317
TI  - Uses of negative pressure wound therapy in orthopedic trauma.
AB  - Negative pressure wound therapy (NPWT) is a useful management tool in the
      treatment of traumatic wounds and high-risk incisions after surgery. Since its
      development nearly 2 decades ago, uses and indications of NPWT have expanded,
      allowing its use in a variety of clinical scenarios. In addition to providing a
      brief summary on its mechanism of action, this article provides a focused,
      algorithmic approach on the use of NPWT by reviewing the available data, the
      appropriate clinical scenarios and indications, and the specific strategies that
      can be used to maximize outcomes. 

PMID- 25771318
TI  - Distal radius-ulna fractures in children.
AB  - Fractures involving the distal radius and ulna are commonly seen in children and
      adolescents. Management of these injuries in pediatric patients should include
      assessment of the neurovascular status of the extremity, associated soft-tissue
      injury, and, most importantly, possible involvement of the physes of the radius
      and ulna. Treatment of these injuries may vary from simple casting and
      radiographic follow-up to urgent reduction and surgical fixation. Regardless of
      the initial treatment plan, the treating surgeon must remain aware of the
      potential for both early and late complications that may affect outcomes. 

PMID- 25771319
TI  - Consequences of single sport specialization in the pediatric and adolescent
      athlete.
AB  - Pediatric and adolescent sports participation has increased with a concomitant
      increase in injuries. Sports have transitioned from recreational to deliberate,
      structured activities wherein success is determined by achievement of 'elite'
      status. This has led to specialization in a single sport with intensive,
      repetitive activity at younger ages causing physical and emotional consequences,
      particularly true for the growing athlete who is particularly susceptible to
      injury. Clinicians caring for this population must understand the epidemiology of
      youth sports specialization, the unique physiology/structure of this age group,
      and the potential physical and emotional consequences. 

PMID- 25771320
TI  - Distal radius fractures: emergency department evaluation and management.
AB  - Musculoskeletal injuries are the second most common cause of presentation to
      emergency departments. Distal radius fractures are an especially common injury
      pattern that often require evaluation and fracture management in an emergency
      department. This article reviews the evaluation of distal radius fractures
      including physical examination and radiographic review. Also discussed is
      management of distal radius fractures including splinting in the setting of an
      emergency department consultation. 

PMID- 25771321
TI  - The management of acute and chronic elbow instability.
AB  - Elbow dislocations are common injuries in both the adult and pediatric
      populations. These injuries include simple dislocation with no associated
      fracture and more complex injuries with bony and ligamentous involvement. Simple
      dislocations are generally stable after reduction and managed with early
      mobilization. Complex dislocations are very unstable and operative intervention
      is usually necessary. Complication risks are greater and outcomes are less
      optimal with complex dislocations. A thorough knowledge of anatomy and
      understanding of the osseous and soft tissue mechanics is essential for proper
      management of these injuries. 

PMID- 25771322
TI  - Ulnar collateral ligament injuries of the thumb: a comprehensive review.
AB  - Injuries to the thumb ulnar collateral ligament (UCL) are common. Failure to
      address the ensuing laxity of the metacarpophalangeal joint can lead to
      compromised grip and pinch, pain, and ultimately osteoarthritis. Instability to
      valgus stress with the lack of a firm end point is a strong indicator of complete
      rupture of the UCL. Nonoperative treatment is reserved for incomplete ruptures of
      the thumb UCL. Operative intervention is typically performed for complete
      ruptures. Repair of acute ruptures and reconstruction for chronic injuries yield
      excellent results. Complications are rare and most patients show preservation of
      motion, key pinch, and grip strength. 

PMID- 25771323
TI  - Evaluation and nonsurgical management of rotator cuff calcific tendinopathy.
AB  - Rotator cuff calcific tendinopathy is a common finding that accounts for about 7%
      of patients with shoulder pain. There are numerous theories on the pathogenesis
      of rotator cuff calcific tendinopathy. The diagnosis is confirmed with
      radiography, MRI or ultrasound. There are numerous conservative treatment options
      available and most patients can be managed successfully without surgical
      intervention. Nonsteroidal anti-inflammatory drugs and multiple modalities are
      often used to manage pain and inflammation; physical therapy can help improve
      scapular mechanics and decrease dynamic impingement; ultrasound-guided needle
      aspiration and lavage techniques can provide long-term improvement in pain and
      function in these patients. 

PMID- 25771325
TI  - Pediatric orthopedics.

PMID- 25771324
TI  - Top five lesions that do not need referral to orthopedic oncology.
AB  - Patients with potential bone and soft tissue tumors can be challenging for
      orthopedic surgeons. Lesions that appear benign can still create anxiety for the
      clinician and patient. However, attention to a few key imaging and clinical
      findings is enough to correctly diagnose five of the most common bone and soft
      tissue lesions: lipoma, enchondroma, osteochondroma, nonossifying fibroma, and
      Paget disease. Accurate identification of these lesions should be within the
      scope of most orthopedic surgeons and, because most of these patients will not
      need surgical treatment, referral to orthopedic oncology will not typically be
      required. 

PMID- 25771326
TI  - Adult reconstruction.

PMID- 25771327
TI  - Trauma.

PMID- 25771328
TI  - Upper extremity.

PMID- 25771329
TI  - Oncology.

PMID- 25771330
TI  - Crohn's disease, the mycobacterium paratuberculosis and the genetic bond: An
      unexpected trio.

PMID- 25771331
TI  - Development of "ultrasound-assisted dynamic extraction" and its combination with
      CCC and CPC for simultaneous extraction and isolation of phytochemicals.
AB  - A new method for the extraction of medicinal herbs termed ultrasonic-assisted
      dynamic extraction (UADE) was designed and evaluated. This technique was coupled
      with counter-current chromatography (CCC) and centrifugal partition
      chromatography (CPC) and then applied to the continuous extraction and online
      isolation of chemical constituents from Paeonia lactiflora Pall (white peony)
      roots. The mechanical parameters, including the pitch and diameter of the shaft,
      were optimized by means of mathematical modeling. Furthermore, the configuration
      and mechanism of online UADE coupled with CCC and CPC were elaborated. The
      stationary phases of the two-phase solvent systems from CCC and CPC were utilized
      as the UADE solution. The extraction solution was pumped into the sample loop and
      then introduced into the CCC column; the target compounds were eluted with the
      lower aqueous phase of the two-phase solvent system. During the CCC separation,
      the extraction solution was continuously fed in the sample loop by turning the
      ten-port valve; the extraction solution was then pumped into the CPC column and
      eluted by the mobile phase of the two-phase solvent system mentioned above. When
      the first cycle of the UADE/CCC/CPC was completed, the second cycle experiment
      could be carried out, and so on. Four target compounds (albiflorin,
      benzoylpaeoniflorin, paeoniflorin, and galloylpaeoniflorin) with purities above
      94.96% were successfully extracted and isolated online using the two-phase
      solvent system comprising ethyl acetate-n-butanol-ethanol-water (1:3.5:2:4.5,
      v/v/v/v). Compared with conventional extraction methods, the instrumental setup
      of the present method offers the advantages of automation and systematic
      extraction and isolation of natural products. 

PMID- 25771332
TI  - Influences of non-uniform pressure field outside bubbles on the propagation of
      acoustic waves in dilute bubbly liquids.
AB  - Predictions of the propagation of the acoustic waves in bubbly liquids is of
      great importance for bubble dynamics and related applications (e.g.
      sonochemistry, sonochemical reactor design, biomedical engineering). In the
      present paper, an approach for modeling the propagation of the acoustic waves in
      dilute bubbly liquids is proposed through considering the non-uniform pressure
      field outside the bubbles. This approach is validated through comparing with
      available experimental data in the literature. Comparing with the previous
      models, our approach mainly improves the predictions of the attenuation of
      acoustic waves in the regions with large kR0 (k is the wave number and R0 is the
      equilibrium bubble radius). Stability of the oscillating bubbles under acoustic
      excitation are also quantitatively discussed based on the analytical solution. 

PMID- 25771333
TI  - Application of hydrodynamic cavitation to improve the biodegradability of mature
      landfill leachate.
AB  - In this study, the application of hydrodynamic cavitation to improve the
      biodegradability of mature landfill leachate was investigated. Three
      configurations of cavitation device were examined and operational parameters of
      the process were selected. The study indicated that the orifice plate with a
      3/10mm diameter conical concentric hole, characterized by the cavitation number
      of 0.033, is a reasonable choice to ensure the enhanced biodegradability of
      mature leachate. Using such a configuration and maintaining 30 recirculation
      passes through the cavitation zone at inlet pressure of 7 bar, the highest
      increase of biodegradability index (BI) of approximately 22% occurred, i.e., from
      the value of 0.046 to 0.056. The FT-IR/PAS analysis confirmed a degradation of
      refractory compounds that typically prevail in mature leachate. An evaluation of
      energy efficiency was made in terms of the actual consumed energy measured by
      using the Kyoritsu KEW6310 Power Quality Tester. A cavitational yield of 9.8 mg
      COD kJ(-1) was obtained for the optimum configuration and 30 recirculation
      passes. Regarding energy efficiency, the application of 10 cavitation cycles
      appeared to be the most profitable. This was due to an almost threefold higher
      cavitational yield of 27.5 mg COD kJ(-1). However, the preferable option should
      be selected by considering a satisfactory effect in the biodegradability
      enhancement.

PMID- 25771334
TI  - Comparison of cell membrane damage induced by the therapeutic ultrasound on human
      breast cancer MCF-7 and MCF-7/ADR cells.
AB  - OBJECTIVES: The aim of this study was to compare the cell membrane damage induced
      by ultrasound at different intensities between MCF-7/ADR cells and MCF-7 cells.
      METHODS: Tumor cells in the culture dishes (35 mm diameter) were exposed to
      planner ultrasound at intensities range from 0.25 W/cm(2) to 0.75 W/cm(2) for
      60s. The viability of cells was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5
      diphenyl tetrazolium bromide (MTT) assay and Guava Viacount assay. The cell
      membrane integrity was estimated by flow cytometry using propidium iodide (PI)
      staining and cellular uptake of fluorescein isothiocyanate-dextran (FD500). The
      membrane lipid peroxidation and membrane fluidity were also specially compared
      between two cell lines in this paper using spectrophotometry. Ultrastructural
      alterations on membrane surface were observed by scanning electron microscopy.
      RESULTS: The ultrasound produced cytotoxicity in both cell lines increased with
      the irradiation intensity increased from 0.25 W/cm(2) to 0.75 W/cm(2). Cell
      membrane permeability and the level of lipid peroxidation were remarkably
      enhanced after ultrasound application. In addition, relatively severe cell damage
      was observed under scanning electron microscopy after 0.75 W/cm(2) ultrasound
      treatment. CONCLUSIONS: Ultrasound exposure decreased MCF-7 and MCF-7/ADR cell
      viability in an intensity-dependent manner and MCF-7/ADR cells were more
      sensitive to ultrasound exposure than MCF-7 cells at the same experimental
      conditions. The declined membrane fluidity in MCF-7/ADR cell may be one of the
      reasons for its increased membrane damage.

PMID- 25771335
TI  - DNA-binding affinity and anticancer activity of beta-carboline-chalcone
      conjugates as potential DNA intercalators: Molecular modelling and synthesis.
AB  - A new series of DNA-interactive beta-carboline-chalcone conjugates have been
      synthesized and evaluated for their in vitro cytotoxicity and DNA-binding
      affinity. It has been observed that most of these new hybrids have shown potent
      cytotoxic activities on A-549 (lung adenocarcinoma) cell lines with IC50 values
      lower than 10 MUM. The hybrid 7b is more effective against some of the selected
      cancer cell lines with IC50 values less than 50 MUM. In addition, compounds 7e,
      7k, 7p-u has displayed significant elevation in DeltaTm of DNA in comparison to
      Adriamycin, suggesting significant interaction and remarkable DNA stabilization.
      The DNA intercalation of these new hybrids has been investigated by fluorescence
      titration, DNA viscosity measurements, molecular docking as well as molecular
      dynamics and the results are in agreement with the thermal denaturation studies.

PMID- 25771336
TI  - Structural and mechanistic characterization of 6S RNA from the hyperthermophilic
      bacterium Aquifex aeolicus.
AB  - Bacterial 6S RNAs competitively inhibit binding of RNA polymerase (RNAP)
      holoenzymes to DNA promoters, thereby globally regulating transcription. RNAP
      uses 6S RNA itself as a template to synthesize short transcripts, termed pRNAs
      (product RNAs). Longer pRNAs (approx. >= 10 nt) rearrange the 6S RNA structure
      and thereby disrupt the 6S RNA:RNAP complex, which enables the enzyme to resume
      transcription at DNA promoters. We studied 6S RNA of the hyperthermophilic
      bacterium Aquifex aeolicus, representing the thermodynamically most stable 6S RNA
      known so far. Applying structure probing and NMR, we show that the RNA adopts the
      canonical rod-shaped 6S RNA architecture with little structure formation in the
      central bulge (CB) even at moderate temperatures (<=37  degrees C). 6S RNA:pRNA
      complex formation triggers an internal structure rearrangement of 6S RNA, i.e.
      formation of a so-called central bulge collapse (CBC) helix. The persistence of
      several characteristic NMR imino proton resonances upon pRNA annealing
      demonstrates that defined helical segments on both sides of the CB are retained
      in the pRNA-bound state, thus representing a basic framework of the RNA's
      architecture. RNA-seq analyses revealed pRNA synthesis from 6S RNA in A.
      aeolicus, identifying 9 to ~17-mers as the major length species. A. aeolicus 6S
      RNA can also serve as a template for in vitro pRNA synthesis by RNAP from the
      mesophile Bacillus subtilis. Binding of a synthetic pRNA to A. aeolicus 6S RNA
      blocks formation of 6S RNA:RNAP complexes. Our findings indicate that A. aeolicus
      6S RNA function in its hyperthermophilic host is mechanistically identical to
      that of other bacterial 6S RNAs. The use of artificial pRNA variants, designed to
      disrupt helix P2 from the 3'-CB instead of the 5'-CB but preventing formation of
      the CBC helix, indicated that the mechanism of pRNA-induced RNAP release has been
      evolutionarily optimized for transcriptional pRNA initiation in the 5'-CB. 

PMID- 25771337
TI  - [Sarcoidosis-lymphoma syndrome].

PMID- 25771338
TI  - [Epidemiology of drug-facilitated sexual assault].

PMID- 25771339
TI  - [Regional recommendations on hepatitis vaccination in human immunodeficiency
      virus infected adult patients in Spain: Evidence-based disparity?].

PMID- 25771340
TI  - [Silicone lymphadenopathy; unexpected cause of adenopathic syndrome].

PMID- 25771341
TI  - British Society for Medical Mycology best practice recommendations for the
      diagnosis of serious fungal diseases.
AB  - Invasive fungal diseases are an important cause of morbidity and mortality in a
      wide range of patients, and early diagnosis and management are a challenge. We
      therefore did a review of the scientific literature to generate a series of key
      recommendations for the appropriate use of microbiological, histological, and
      radiological diagnostic methods for diagnosis of invasive fungal diseases. The
      recommendations emphasise the role of microscopy in rapid diagnosis and
      identification of clinically significant isolates to species level, and the need
      for susceptibility testing of all Aspergillus spp, if treatment is to be given.
      In this Review, we provide information to improve understanding of the importance
      of antigen detection for cryptococcal disease and invasive aspergillosis, the use
      of molecular (PCR) diagnostics for aspergillosis, and the crucial role of
      antibody detection for chronic and allergic aspergillosis. Furthermore, we
      consider the importance of histopathology reporting with a panel of special
      stains, and emphasise the need for urgent (<48 hours) and optimised imaging for
      patients with suspected invasive fungal infection. All 43 recommendations are
      auditable and should be used to ensure best diagnostic practice and improved
      outcomes for patients. 

PMID- 25771342
TI  - Detecting volatile compounds from Kraft lignin degradation in the headspace of
      microbial cultures by selected ion flow tube mass spectrometry (SIFT-MS).
AB  - Selected Ion Flow Tube Mass Spectrometry (SIFT-MS) was used to quantify methanol
      and other volatile compounds in the headspace of one bacterial and 12 fungal
      lignin-degrading microbial cultures. Cultures were grown in 250 mL Erlenmeyer
      flasks capped with aluminum foil containing 40 mL of nutrient media using Kraft
      lignin (0.3% w/v) as the sole carbon source. Analysis was done using SIFT-MS with
      H3O(+) and NO(+) precursors. Product ions were identified with multiple ion mode
      (MIM). Full scan (FS) mode was used to identify other compounds of interest.
      Absidia cylindrospora, Ischnoderma resinosum and Pholiota aurivella increased
      headspace methanol concentration by 136 ppb, 1196 ppb and 278 ppb, respectively,
      while Flammulina velutipes and Laetiporus sulphureus decreased concentration
      below ambient levels. F. velutipes and L. sulphureus were found to produce
      products of methanol oxidation (formaldehyde and formic acid) and were likely
      metabolizing methanol. Some additional unidentified compounds generated by the
      fungal cultures are intriguing and will require further study. SIFT-MS can be
      used to quantify methanol and other volatile compounds in the headspace of
      microbial cultures and has the potential to be a rapid, sensitive, non-invasive
      tool useful in elucidating the mechanisms of lignin degradative pathways.

PMID- 25771343
TI  - Monitoring Campylobacter in the poultry production chain-from culture to genes
      and beyond.
AB  - Improved monitoring tools are important for the control of Campylobacter bacteria
      in poultry production. Standardized reference culture methods issued by national
      and international standardization organizations are time-consuming, cumbersome
      and not amenable to automation for screening of large numbers of samples. The
      ultimate goal for rapid monitoring of Campylobacter is to prevent contaminated
      meat from entering the food market. Currently, real-time PCR is fulfilling
      abovementioned criteria to a certain extent. Further development of real-time
      PCR, microarray PCR, miniaturized biosensors, chromatographic techniques and DNA
      sequencing can improve our monitoring capacity at a lower cost. Combined with
      innovative sampling and sample treatment, these techniques could become realistic
      options for on-farm and liquid-sample monitoring at slaughterhouses. 

PMID- 25771344
TI  - Elevated ozone and nitrogen deposition affect nitrogen pools of subalpine
      grassland.
AB  - In a free-air fumigation experiment with subalpine grassland, we studied long
      term effects of elevated ozone (O3) and nitrogen (N) deposition on ecosystem N
      pools and on the fate of anthropogenic N. At three times during the seventh year
      of exposure, N pools and recovery of a stable isotope tracer ((15)N) were
      determined in above- and belowground plant parts, and in the soil. Plants were
      much better competitors for (15)N than soil microorganisms. Plant N pools
      increased by 30-40% after N addition, while soil pools remained unaffected,
      suggesting that most of the extra N was taken up and stored in plant biomass,
      thus preventing the ecosystem from acquiring characteristics of eutrophication.
      Elevated O3 caused an increase of N in microbial biomass and in stabilized soil
      N, probably resulting from increased litter input and lower litter quality.
      Different from individual effects, the interaction between the pollutants
      remained partly unexplained. 

PMID- 25771345
TI  - Pesticide leaching through sandy and loamy fields - long-term lessons learnt from
      the Danish Pesticide Leaching Assessment Programme.
AB  - The European Union authorization procedure for pesticides includes an assessment
      of the leaching risk posed by pesticides and their degradation products (DP) with
      the aim of avoiding any unacceptable influence on groundwater. Twelve-year's
      results of the Danish Pesticide Leaching Assessment Programme reveal shortcomings
      to the procedure by having assessed leaching into groundwater of 43 pesticides
      applied in accordance with current regulations on agricultural fields, and 47 of
      their DP. Three types of leaching scenario were not fully captured by the
      procedure: long-term leaching of DP of pesticides applied on potato crops
      cultivated in sand, leaching of strongly sorbing pesticides after autumn
      application on loam, and leaching of various pesticides and their DP following
      early summer application on loam. Rapid preferential transport that bypasses the
      retardation of the plow layer primarily in autumn, but also during early summer,
      seems to dominate leaching in a number of those scenarios. 

PMID- 25771347
TI  - Optical coherence tomography in the diagnosis of scleritis and episcleritis.
AB  - PURPOSE: To describe the optical coherence tomography (OCT) findings in eyes with
      active anterior scleritis and compare the findings to those with episcleritis and
      normal controls. DESIGN: Prospective evaluation of a diagnostic test. METHODS: We
      included a total of 30 eyes of 30 patients with unilateral anterior scleral or
      episcleral inflammation. The contralateral 30 eyes with no active ocular disease
      served as controls. OCT was performed over the anterior sclera in the inflamed
      area on all cases. The OCT images were analyzed to determine the thickness of the
      sclera and the presence or absence of scleral hyporeflective areas representing
      intrascleral edema. RESULTS: There were 17 male and 13 female patients. The mean
      age was 43 years with an age range of 21-77 years. Eighteen patients had anterior
      scleritis and 12 patients had episcleritis. The mean transconjunctival scleral
      thickness was 747 MUm (SD +/- 68.97) with a range of 616-877 MUm in normal eyes,
      882 MUm (SD +/- 87.35) with a range of 773-1089 MUm in patients with scleritis,
      and 825 MUm (SD +/- 85.57) with a range of 718-949 MUm in patients with
      episcleritis. CONCLUSIONS: Patients with active anterior scleritis showed
      increased thickness of the sclera and presence of intrascleral hyporeflective
      areas of edema by OCT compared to patients with episcleritis and normal eyes. OCT
      adds both qualitative and quantitative information to diagnosis and monitoring of
      patients with scleritis.

PMID- 25771348
TI  - Effect of cooling rate and equilibration time on pre-freeze and post-thaw
      survival of buck sperm.
AB  - Survival of buck sperm is affected due to duration and temperature of stages of
      refrigerated or frozen storage. This study investigated interactive effect of
      cooling rates (moderate; MC and rapid cooling; RC); and equilibration times (0,
      2, 4 and 8h) on survival before freezing at 4 degrees C and post-thaw quality of
      buck sperm. Semen was collected (three Beetal bucks; replicates=6), pooled and
      diluted with Tris-citrate extender. Pooled semen samples were subjected to either
      RC (-2.2 degrees C/min) or MC (-0.3 degrees C/min) from 37 degrees C to 4 degrees
      C in separate aliquots and further equilibrated at 4 degrees C for 8h. Semen was
      frozen using standard procedure after completion of each equilibration period
      i.e. 0, 2, 4 and 8h. Semen was evaluated for motility, viability, plasma membrane
      integrity (PMI) and normal apical ridge (NAR) before freezing and after thawing.
      The survival time (time for survival above threshold limit i.e. 60%) at 4 degrees
      C, of motility and PMI was observed 5 and 6h respectively in RC group while >8h
      in MC group. Rate of decline (slope) in motility and viability was higher
      (P<0.05) in RC overtime during equilibration at 4 degrees C while PMI and NAR
      declined at equal rate in both cooling groups. Post-thaw motility and NAR were
      higher (P<0.05) in MC when equilibrated for 2-8h while viability and PMI of RC
      was observed equal to MC group. In conclusion, survival of buck sperm is higher
      when cooled with moderate rate. However, RC can maintain post-thaw sperm
      viability and PMI equal to MC when equilibrated for 2-8h. The methods should be
      explored to maintain motility and NAR during rapid cooling of buck sperm. 

PMID- 25771346
TI  - The cellular and molecular progression of mitochondrial dysfunction induced by
      2,4-dinitrophenol in developing zebrafish embryos.
AB  - The etiology of mitochondrial disease is poorly understood. Furthermore,
      treatment options are limited, and diagnostic methods often lack the sensitivity
      to detect disease in its early stages. Disrupted oxidative phosphorylation
      (OXPHOS) that inhibits ATP production is a common phenotype of mitochondrial
      disorders that can be induced in zebrafish by exposure to 2,4-dinitrophenol
      (DNP), a FDA-banned weight-loss agent and EPA-regulated environmental toxicant,
      traditionally used in research labs as an uncoupler of OXPHOS. Despite the DNP
      induced OXPHOS inhibition we observed using in vivo respirometry, the development
      of the DNP-treated and control zebrafish were largely similar during the first
      half of embryogenesis. During this period, DNP-treated embryos induced gene
      expression of mitochondrial and nuclear genes that stimulated the production of
      new mitochondria and increased glycolysis to yield normal levels of ATP. DNP
      treated embryos were incapable of sustaining this mitochondrial biogenic response
      past mid-embryogenesis, as shown by significantly lowered ATP production and ATP
      levels, decreased gene expression, and the onset of developmental defects.
      Examining neural tissues commonly affected by mitochondrial disease, we found
      that DNP exposure also inhibited motor neuron axon arbor outgrowth and the proper
      formation of the retina. We observed and quantified the molecular and
      physiological progression of mitochondrial dysfunction during development with
      this new model of OXPHOS dysfunction, which has great potential for use in
      diagnostics and therapies for mitochondrial disease. 

PMID- 25771349
TI  - The Efficacy of Ankle-Foot Orthoses on Improving the Gait of Children With
      Diplegic Cerebral Palsy: A Multiple Outcome Analysis.
AB  - BACKGROUND: Ankle-foot orthosis (AFO) prescriptions are common for patients
      diagnosed with cerebral palsy (CP). Typical treatment objectives are to improve
      ankle-foot function and enhance general gait quality. OBJECTIVE: To determine the
      effectiveness of AFOs for improving the gait of children with diplegic CP.
      DESIGN: Retrospective analysis. SETTING: Primary clinical care facility.
      PARTICIPANTS: Data were used from 601 visits for 378 individuals (age at visit:
      9.8 +/- 3.8 years [mean +/- standard deviation]) who wore either a solid, hinged,
      or posterior leaf spring AFO design. Participants had a diagnosis of diplegic CP,
      wore the same AFO design bilaterally, and had 3-dimensional gait analysis data
      collected while walking both barefoot and with AFOs during a single session.
      METHODS: Differences between walking with AFOs and walking barefoot were used as
      outcome measures. Statistical analysis consisted of paired t-tests and
      multivariate analysis of variance scores to determine significance, main effects,
      and interactions of AFO design, ambulation type (walking with/without assistive
      devices), and barefoot level on each outcome. Minimal clinically important
      differences from the literature determined clinical significance. OUTCOME
      MEASURES: Gait Deviation Index (GDI), ankle Gait Variable Score, knee Gait
      Variable Score, nondimensional speed, and nondimensional step length. RESULTS:
      Only step length exhibited clinically meaningful improvements for the average AFO
      user. Changes in step length, speed, and GDI all were statistically significant
      (P < .001). Barefoot outcome levels were the most consistent influence on outcome
      changes. AFO design was shown to effect changes in speed and ankle function,
      whereas ambulation type was shown to affect GDI change. CONCLUSIONS: Current AFO
      prescription methodologies for children with CP result in consistent gait
      improvements for step length only. This study emphasizes the need to develop more
      effective AFO prescription algorithms in an effort to improve the efficacy of
      AFOs on general gait quality via optimizing patient selection or AFO design.

PMID- 25771350
TI  - Quantification of Lumbar Stability During Wall Plank-and-Roll Activity Using
      Inertial Sensors.
AB  - OBJECTIVE: To develop a simple method of quantifying dynamic lumbar stability by
      evaluating postural changes of the lumbar spine during a wall plank-and-roll
      (WPR) activity while maintaining maximal trunk rigidity. DESIGN: A descriptive,
      exploratory research with a convenience sample. SETTING: A biomechanics
      laboratory of a tertiary university hospital. PARTICIPANTS: Sixteen healthy young
      subjects (8 men and 8 women; 30.7 +/- 6.8 years old) and 3 patients (2 men 46 and
      50 years old; 1 woman 54 years old) with low back pain (LBP). METHODS: The
      subjects performed the WPR activity with 2 inertial sensors attached on the
      thoracic spine and sacrum. Relative angles between the sensors were calculated to
      characterize lumbar posture in 3 anatomical planes: axial twist (AT), kyphosis
      lordosis (KL), or lateral bending (LB). Isokinetic truncal flexion and extension
      power were measured. MAIN OUTCOME MEASURES: AT, KL, and LB were compared between
      the initial plank and maximal roll positions. Angular excursions were compared
      between males and females and between rolling sides, and tested for correlation
      with isokinetic truncal muscle power. Patterns and consistencies of the lumbar
      postural changes were determined. Lumbar postural changes of each patient were
      examined in the aspects of pattern and excursion, considering those from the
      healthy subjects as reference. RESULTS: AT, KL, and LB were significantly changed
      from the initial plank to the maximal roll position (P < .01); that is, the
      thoracic spine rotated further, lumbar lordosis increased, and the thoracic spine
      was bent away from the wall by 6.9 degrees  +/- 12.0 degrees , 9.5 degrees  +/-
      6.5 degrees , and 7.9 degrees  +/- 4.9 degrees , respectively. The patterns and
      amounts of lumbar postural changes were not significantly different between the
      rolling sides or between male and female participants, except that the excursion
      in AT was larger on the dominant rolling side. The excursions were not related to
      isokinetic truncal muscle power. The 3 LBP patients showed varied deviations in
      pattern and excursion from the average of the healthy subjects. CONCLUSIONS:
      Certain amounts and patterns of lumbar postural changes were observed in healthy
      young subjects, with no significant variations based on gender, rolling side, or
      truncal muscle power. Application of the evaluation on LBP patients revealed
      prominent deviations from the healthy postural changes, suggesting potential
      clinical applicability. Therefore, with appropriate development and case
      stratification, we believe that the quantification of lumbar postural changes
      during WPR activity can be used to assess dynamic lumbar stability in clinical
      practice.

PMID- 25771351
TI  - On the calibration of a radon exhalation monitor based on the electrostatic
      collection method and accumulation chamber.
AB  - The radon exhalation rate can be obtained quickly and easily from the evolution
      of radon concentration over time in the accumulation chamber. Radon monitoring
      based on the electrostatic collection method is not interfered with by (220)Rn.
      In this paper, we propose that the difference between radon and (218)Po
      concentrations in the measurement cell of this kind of radon exhalation monitor
      is the main system error, and it changes with time and different effective decay
      constants. Based on the results of simulation experiments, we propose that the
      calibration factor obtained from the suitable experiment cannot completely
      correct the system error, even if it is useful to reduce the measurement error.
      The better way for reducing measurement error is to use the new measurement model
      which we have proposed in recent years. 

PMID- 25771352
TI  - Embryonic health: new insights, mHealth and personalised patient care.
AB  - The worldwide epidemic of non-communicable diseases (NCD), including obesity, is
      a burden to which poor lifestyles contribute significantly. Events in early life
      may enhance susceptibility to NCD, with transmission into succeeding generations.
      This may also explain, in part, why interventions in adulthood are less effective
      to reduce NCD risk. New insights reveal that the early embryo, in particular, is
      extremely sensitive to signals from gametes, trophoblastic tissue and
      periconception maternal lifestyles. Embryonic size and growth as determinants of
      embryonic health seem to impact future health. A relatively small embryo for
      gestational age is associated with pregnancy complications, as well as with the
      risk of early features of NCD in childhood. Although personal lifestyles are
      modifiable, they are extremely difficult to change. Therefore, adopting a life
      course approach from the periconception period onwards and integrated into
      patient care with short-term reproductive health benefits may have important
      implications for future prevention of NCD. The current reproductive population is
      used to Internet and social media. Therefore, they can be reached via mobile
      phone (mHealth) platforms that provide personalised lifestyle (pre)pregnancy
      programs. This will offer opportunities and possibly great benefits for the
      health of current and succeeding generations. 

PMID- 25771353
TI  - Verbal memory and literacy outcomes one year after pediatric temporal lobectomy:
      a retrospective cohort study.
AB  - OBJECTIVE: In children with temporal lobe epilepsy (TLE), temporal lobectomy (TL)
      is a treatment of choice for those children with seizure that are difficult to
      control with medication. Semantic memory is dependent on functional integrity of
      the temporal lobes and is thought to be critical for development of literacy
      skills. However, little is known about semantic memory and literacy outcomes post
      TL in children. METHOD: In this retrospective cohort study, 40 children with TLE
      were administered tests of memory and literacy pre-TL and 1year post-TL in one
      hospital between 1996 and 2011. RESULTS: One year post-TL, 60% of the children
      became seizure-free. A significant decline was found in one aspect of semantic
      memory (naming) in children who underwent left TL. In addition, a significant
      drop was also evident in one aspect of literacy (reading accuracy), irrespective
      of the side of surgery. These declines were related neither to each other nor to
      epilepsy variables including seizure outcome. CONCLUSIONS: This is the largest
      pediatric outcome study of memory and literacy skills to date and shows that TL
      is associated with a risk of a mild drop in specific aspects of semantic memory
      (naming, following left TL) and reading accuracy, while other areas of memory and
      literacy remain unchanged.

PMID- 25771354
TI  - Psychoneuropharmacological activities and chemical composition of essential oil
      of fresh fruits of Piper guineense (Piperaceae) in mice.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Piper guineense Schum & Thonn (Piperaceae) is a
      medicinal plant used in the Southern States of Nigeria to treat fever, mental
      disorders and febrile convulsions. AIMS OF THE STUDY: This study aims at
      determining the chemical composition and the central nervous system (CNS)
      activities of the essential oil obtained from the plant's fresh fruits in order
      to rationalize its folkloric use. MATERIALS AND METHODS: Essential oil of P.
      guineense (EOPG) obtained by hydrodistillation was analysed by GC/MS. EOPG (50
      200mg/kg, i.p.) was evaluated for behavioural, hypothermic, sedative, muscle
      relaxant, anti-psychotic and anticonvulsant activities using standard procedures.
      RESULTS AND DISCUSSION: Analysis of the oil reveals 44 compounds of which 30
      compounds constituting 84.7% were identified. The oil was characterized by
      sesquiterpenoids (64.4%) while only four monoterpeneoids (21.3%) were found
      present in the oil. Major compounds identified were beta-sesquiphellandrene
      (20.9%), linalool (6.1%), limonene (5.8%), Z-beta-bisabolene (5.4%) and alpha
      pinene (5.3%). The EOPG (50-200mg/kg, i.p.) caused significant (p<0.01)
      inhibition on rearing {F(4,20)=43}, locomotor {F(4,20)=22} activity and decreased
      head dips in hole board {F(4,20)=7} indicating CNS depressant effect; decreased
      rectal temperature {F(4,20)=7-16}, signifying hypothermic activity; decreased
      ketamine-induced sleep latency {F(4,20)=7.8} and prolonged total sleeping time
      {F(4,20)=8.8}, indicating sedative effect; reduced muscular tone on the hind-limb
      grip test {F(4,20)=22}, inclined board {F(4,20)=4-49} and rota rod {F(4,20)=13
      106}, implying muscle relaxant activity; induced catalepsy {F(4,20)=47-136},
      inhibited apomorphine-induced climbing behaviour {F(4,20)=9} and inhibited
      apomorphine-induced locomotor {F(4,20)=16}, suggesting anti-psychotic effect; and
      protected mice against pentylenetetrazole-induced convulsions, indicating
      anticonvulsant potential. CONCLUSION: The most abundant component of the fresh
      fruits essential oil of P. guineense was beta-sesquiphellandrene (20.9%); and the
      oil possesses CNS depressant, hypothermic, sedative, muscle relaxant,
      antipsychotic and anticonvulsant activities, thus providing scientific basis for
      its ethnomedicinal applications.

PMID- 25771355
TI  - An ethnobotanical survey of medicinal plants in western part of central Taurus
      Mountains: Aladaglar (Nigde - Turkey).
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: With this study, we aimed to document traditional
      uses of medicinal plants in the western part of Aladaglar/Nigde. MATERIALS AND
      METHODS: This study was conducted between 2003 and 2005. The research area was in
      the western part of the Aladaglar mountains. The settlements in Aladaglar (5
      towns and 10 villages) were visited during the field work. The plants collected
      by the help of medicinal plant users. The plants were identified and voucher
      specimens prepared. These voucher specimens were kept at the Herbarium of
      Istanbul University Faculty of Pharmacy (ISTE). We collected the information by
      means of semi-structured interviews with 170 informants (90 men and 80 women). In
      addition, the relative importance value of the species was determined and the
      informant consensus factor (FIC) was calculated for the medicinal plants
      researched in the study. RESULTS: According to the results of the identification,
      among 126 plants were used by the inhabitants and 110 species belonging to 40
      families were used for medicinal purposes. Most of the medicinal plants used in
      Aladaglar/Nigde belong to the families Lamiaceae (25 species), Asteraceae (16
      species), Apiaceae (7 species), Fabaceae (6 species) and Brassicaceae (5
      species). The most commonly used plant species were Hypericum perforatumThymus
      sipyleus var. sipyleus, Rosa canina, Urtica dioica, Malva neglecta, Thymus
      leucotrichus, Salix alba, Mentha longifolia, Berberis crataegina, Juniperus
      oxycedrus, Viscum album subsp. abietis, Allium rotundum and Taraxacum stevenii.
      The most common preparations were infusion and decoction. The traditional
      medicinal plants have been mostly used for the treatment of cardiovascular
      diseases (86%), hemorrhoids (79%), urinary diseases (69%), diabetes (68%) and
      respiratory diseases (61%). CONCLUSION: The use of traditional medicine was still
      widespread among the inhabitants of Aladaglar mountains/Nigde region. Due to the
      lack of medical facilities in the villages of Aladaglar mountains, local people
      prefer herbal treatment rather than medical treatment. This study identified not
      only the wild plants collected for medical purposes by local people of
      Aladaglar/Nigde, but also the uses and local names of these plants. This paper
      helps to preserve valuable information that may otherwise be lost to future
      generations.

PMID- 25771356
TI  - Analgesic, anti-inflammatory and antipyretic activities of the methanol leaf
      extract of Dalbergia saxatilis Hook.F in rats and mice.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: The decoction of the leaves of Dalbegia saxatilis
      is used in Traditional Medicine for various ailments such as cough, small pox,
      skin lesions, bronchial ailments and toothache. The study is aimed at evaluating
      the analgesic, anti-inflammatory, and antipyretic effects of D. saxatilis to
      provide scientific basis for its use. MATERIALS AND METHODS: Phytochemical
      screening and evaluation of oral median lethal dose was carried out on the
      methanol leaf extract of the plant. Analgesic activity using acetic acid induced
      writhing and hot plate method in mice, anti-inflammatory activity using
      carrageenan induced paw oedema in rats, and antipyretic activity using Brewer's
      yeast induced pyrexia in rats were evaluated at 250mg/kg, 500mg/kg, and 1000mg/kg
      doses of the extract. RESULTS: The oral median lethal dose was found to be above
      5000mg/kg. The extract was found to contain alkaloids, flavonoids, tannins,
      saponins, cardiac glycosides, and triterpenes. The extract and the standard drug
      (Aspirin) significantly decreased the number of writhes caused by acetic acid at
      p<0.001. There was statistical significant increase in reaction time in standard
      group, extract 250mg/kg, and 1000mg/kg from 60 min at p<0.05 and p<0.01, from 30
      min in 500mg/kg group at p<0.05 and p<0.01 compared with 0 min. A statistical
      significant decreases in paw sizes at p<0.05 and p<0.01 compared to the peak
      increase in both standard and test groups was observed. Statistical significant
      reduction in rectal temperatures was observed in standard group at 21 and 23 h,
      and in 500mg/kg and 1000mg/kg doses of the extract at 23 h at p<0.05 compared
      with the 19h. CONCLUSION: The results obtained indicated potential analgesic,
      anti-inflammatory and antipyretic effects of the methanol leaf extract of D.
      saxatilis observed at doses tested which support the claim for the traditional
      use of the plant in treatment of toothache.

PMID- 25771357
TI  - Resource investigation of traditional medicinal plant Panax japonicus (T.Nees)
      C.A. Mey and its varieties in China.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Panax japonicus, the perennial herb in the
      Araliaceae family, was used as the natural medicinal herb by Chinese traditional
      doctors for more than thousand years. Its rhizome was mainly used as a tonic,
      anti-inflammatory and hemostatic agent in China. Most of the therapeutic effects
      of P. japonicus had been reported due to the presence of tetracyclic or
      pentacyclic triterpene saponins. Volatile oil, polysaccharides and amino acids
      had also been found in P. japonicus species and reported in the pharmacological
      functions. AIM OF THE STUDY: A three-year survey was conducted to determine the
      current resource status of P. japonicus (T.Nees) C. A. Mey and its varieties (P.
      japonicus var. major (Burkill) C.Y.Wu & Feng and P. japonicus var. bipinnatifidus
      (Seem.) C.Y.Wu & Feng) in 10 provinces of southern and southwestern China.
      METHODS AND RESULTS: Whole plants were sampled at 64 sites. Resource
      distribution, habitat type, morphological variation and market trend of them were
      studied and discussed. The natural resource in China is rarely available due to
      extensive exploitation and continual environment deterioration in recent decades,
      Abundance of P. japonicus was much lower than previous records, mainly found in
      Hubei, Sichuan, Guizhou and Yunnan province. Wild resources of P.japonicus var.
      major and P.japonicus var. bipinnatifidus were even scarcer, only found in
      Guizhou and Yunan province. Despite their dramatic rise of market trend, the
      artificial cultivation of them was still not fully developed in China, but
      progressed rapidly in Hubei province. CONCLUSION: In this study, we synthesized
      our understandings of the current resource state of P. japonicus's existence,
      variation and cultivation in China. This study will aid further investigations
      and increased protection of these plants, which are very valuable to traditional
      herbal medicine.

PMID- 25771358
TI  - Miniaturized multi-coil arrays for functional planar imaging with a single-sided
      NMR sensor.
AB  - Nowadays most low-field NMR sensors, such as the single-sided Profile NMR
      MOUSE(r), still suffer from poor sensitivity, either resulting from low magnetic
      field strengths and correspondingly low NMR frequencies, or lack of sensitivity.
      Generally, micro-coils can improve sensitivity, but due to their small size, and
      thus small inductance, they are mainly used for high-field NMR. Their main
      application field is parallel imaging, where those coils are typically assembled
      to receive-only coil-arrays and increase the field-of-view. Prominent signal
      combination techniques such as GRAPPA and SENSE are used to combine the spatially
      independent NMR signals to images in order to increase acquisition speed. A
      decisive disadvantage of today's single-sided NMR probes is the limited
      accessibility for NMR imaging. Although it is possible to use flat gradient coils
      on top of the NMR-MOUSE(r) to apply imaging techniques, such images can only be
      recorded with very long acquisition times, excluding the NMR-MOUSE(r) for lateral
      imaging of time-dependent processes. In this study sensitivity improved micro
      structured RF coils, optimized for low frequencies, and correspondingly arrays of
      these coils, were employed to improve sensitivity and gave access to lateral
      spatial resolution within the sensitive plane at several observation points at
      the same time. Recently developed three- and four-coil arrays were combined with
      a Profile NMR-MOUSE(r) and characterized in terms of coil coupling, noise
      correlation and signal combination. The three-coil array was used for lateral
      imaging of moisture transport in travertine rock samples and to study the one
      dimensional drying of paint. 

PMID- 25771359
TI  - Obese individuals have higher preference and sensitivity to odor of chocolate.
AB  - The worldwide epidemic of obesity has inspired a great deal of research into its
      causes and consequences. It is therefore surprising that so few studies have
      examined such a fundamental part of eating behavior: our sense of smell. The aim
      of the present study was to examine the differences in olfaction in obese and
      nonobese individuals. Participants (n = 40) categorized as obese (body mass index
      >= 30) or nonobese (body mass index < 30) completed a standardized olfactory
      threshold test to an ecologically valid food-related odor (chocolate), followed
      by a taste test. We found that compared with those not obese, obese individuals
      rated the chocolate odor as more pleasant and were substantially more sensitive
      to the odor. There was also evidence that their sense of taste was more acute for
      sour and salty tastants. Correlational analyses further revealed that those
      measures of olfaction and taste were positively associated with body mass index.
      These findings suggest that obese individuals show increased sensitivity and
      preference for an odor associated with energy dense foods. They also suggest that
      differences in our sense of smell offer a promising area for future research in
      obesity. 

PMID- 25771361
TI  - An empirical evaluation of two theoretically-based hypotheses on the directional
      association between self-worth and hope.
AB  - Fostering self-worth and hope are important goals of positive youth development
      (PYD) efforts, yet intervention design is complicated by contrasting theoretical
      hypotheses regarding the directional association between these constructs.
      Therefore, within a longitudinal design we tested: (1) that self-worth predicts
      changes in hope (self theory; Harter, 1999), and (2) that hope predicts changes
      in self-worth (hope theory; Snyder, 2002) over time. Youth (N = 321; Mage = 10.33
      years) in a physical activity-based PYD program completed surveys 37-45 days
      prior to and on the second day and third-to-last day of the program. A latent
      variable panel model that included autoregressive and cross-lagged paths
      indicated that self-worth was a significant predictor of change in hope, but hope
      did not predict change in self-worth. Therefore, the directional association
      between self-worth and hope is better explained by self-theory and PYD programs
      should aim to enhance perceptions of self-worth to build perceptions of hope. 

PMID- 25771360
TI  - Minibeam therapy with protons and light ions: physical feasibility and potential
      to reduce radiation side effects and to facilitate hypofractionation.
AB  - PURPOSE: Despite several advantages of proton therapy over megavoltage x-ray
      therapy, its lack of proximal tissue sparing is a concern. The method presented
      here adds proximal tissue sparing to protons and light ions by turning their
      uniform incident beams into arrays of parallel, small, or thin (0.3-mm) pencil or
      planar minibeams, which are known to spare tissues. As these minibeams penetrate
      the tissues, they gradually broaden and merge with each other to produce a solid
      beam. METHODS AND MATERIALS: Broadening of 0.3-mm-diameter, 109-MeV proton pencil
      minibeams was measured using a stack of radiochromic films with plastic spacers.
      Monte Carlo simulations were used to evaluate the broadening in water of
      minibeams of protons and several light ions and the dose from neutron generated
      by collimator. RESULTS: A central parameter was tissue depth, where the beam full
      width at half maximum (FWHM) reached 0.7 mm, beyond which tissue sparing
      decreases. This depth was 22 mm for 109-MeV protons in a film stack. It was also
      found by simulations in water to be 23.5 mm for 109 MeV proton pencil minibeams
      and 26 mm for 116 MeV proton planar minibeams. For light ions, all with 10 cm
      range in water, that depth increased with particle size; specifically it was 51
      mm for Li-7 ions. The ~2.7% photon equivalent neutron skin dose from the
      collimator was reduced 7-fold by introducing a gap between the collimator and the
      skin. CONCLUSIONS: Proton minibeams can be implemented at existing particle
      therapy centers. Because they spare the shallow tissues, they could augment the
      efficacy of proton therapy and light particle therapy, particularly in treating
      tumors that benefit from sparing of proximal tissues such as pediatric brain
      tumors. They should also allow hypofractionated treatment of all tumors by
      allowing the use of higher incident doses with less concern about proximal tissue
      damage.

PMID- 25771362
TI  - Consequences of meta-stable (177m)Lu admixture in (177)Lu for patient dosimetry.
AB  - Lutetium-177 ((177)Lu) is a rare earth metal in the lanthanides series which
      decays by beta emission with a half life of 6.647 days to three excited states
      and the ground state of (177)Hf. When (177)Lu is produced by neutron capture in
      (176)Lu, inevitably an admixture is formed of the long-lived isomer (177)mLu. As
      its half-life of 160.4 days is so much longer than that of (177)Lu, concerns are
      raised on its possible enhancement in radiation dose to the patient treated with
      (177)Lu-DOTA-octreotate. This report evaluates this possible enhancement of the
      absorbed dose, based on the published pharmacokinetic profile of (177)Lu-DOTA
      octreotate and assuming an admixture of 1 kBq (177)mLu /MBq (177)Lu (0.1%). 

PMID- 25771363
TI  - Theranostic Radiopharmaceuticals Based on Gold Nanoparticles Labeled with (177)Lu
      and Conjugated to Peptides.
AB  - Gold nanoparticles (AuNPs) have been proposed for a variety of medical
      applications such as localized heat sources for cancer treatment and drug
      delivery systems. The conjugation of peptides to AuNPs produces stable multimeric
      systems with target-specific molecular recognition. Lutetium- 177 ((177)Lu) has
      been successfully used in peptide radionuclide therapy. Recently, (177)Lu-AuNPs
      conjugated to different peptides have been proposed as a new class of theranostic
      radiopharmaceuticals. These radioconjugates may function simultaneously as
      molecular imaging agents, radiotherapy systems and thermal-ablation systems. This
      article covers advancements in the design, synthesis, physicochemical
      characterization, molecular recognition assessment and preclinical therapeutic
      efficacy of gold nanoparticles radiolabeled with (177)Lu and conjugated to RGD (
      Arg-Gly-Asp-), Lys(3)-Bombesin and Tat(49-57) peptides. 

PMID- 25771364
TI  - Theranostic Applications of Lutetium-177 in Radionuclide Therapy.
AB  - Lutetium-177 has been widely discussed as a radioisotope of choice for targeted
      radionuclide therapy. The simultaneous emission of imageable gamma photons [208
      keV (11%) and 113 keV (6.4%)] along with particulate beta(-) emission [beta(max)
      = 497 keV] makes it a theranostically desirable radioisotope. In the present
      article, the possibility of using two 177Lu-based agents viz. 177Lu-EDTMP and
      177Lu-DOTATATE for theranostic applications in metastatic bone pain palliation
      (MBPP) and peptide receptor radionuclide therapy (PRRT), have been explored. In
      the case of 177Lu-EDTMP, the whole-body images obtained are compared with those
      recorded using 99mTc-MDP in the same patient. On the other hand, pre-therapy
      images acquired with 177Lu-DOTA-TATE are compared with similar images obtained
      with standard agents, such as 99mTc-HYNIC-TOC (SPECT) and 68Ga-DOTA-TOC (PET) in
      the same patient. The advantage of the long physical half-life (T1/2) of 177Lu
      has been utilized in mapping the pharmacokinetics of two additional agents, 177Lu
      labeled hydroxyapatite (HA) in radiation synovectomy of knee joints and 177Lu-HA
      for therapy of hepatocellular carcinoma. Results of these multiple studies
      conclusively document the potential of 177Lu as a theranostic radioisotope.

PMID- 25771365
TI  - Radioimmunotherapy of Metastatic Prostate Cancer with 177Lu-DOTAhuJ591 Anti
      Prostate Specific Membrane Antigen Specific Monoclonal Antibody.
AB  - Prostate specific membrane antigen (PSMA) is the single most well-validated
      prostate cancer (PCa)-specific cell membrane antigen known. It is present in high
      levels in 95% of PCa, and is an ideal target to develop radiopharmaceuticals for
      imaging studies and radionuclide therapy. Humanized J591 monoclonal antibody
      (mAb) binds specifically with nanomolar affinity to the extracellular domain of
      PSMA. After binding, the PSMA-antibody complex is rapidly internalized,
      increasing the potential utility of PSMA as a target for the delivery of mAb
      conjugated radionuclides or cytotoxins. J591 mAb was labeled with 177Lu at a high
      specific activity (10-30 mCi/mg) using DOTA as the bifunctional chelate. The
      preclinical data in PSMA positive xenografts, strongly suggested that 177;Lu-J591
      mAb is an ideal radiopharmaceutical for RIT of metastatic PCa. Since October
      2000, five clinical studies (phase I and II) were performed in subjects with
      metastatic castration-resistant prostate cancer (CRPC) using 177Lu-J591. The
      methodology and the results of these clinical studies are briefly reviewed in
      this article. The maximum tolerated dose (MTD) as a single dose was 70 mCi2.
      Based on dose fractionation (DF), MTD was 90 mCi/m2(2 doses of 45 mCi/m2, 2 wks
      apart). Phase II study in patients with progressive metastatic CRPC, at a dose of
      65- 70 mCi/m2 resulted in significant PSA declines in 60% of the patients. While
      myelosuppression was the dose limiting toxicity, DF alone or in combination with
      docetaxel also resulted in significant PSA declines with much less toxicity.
      177Lu imaging studies demonstrated accurate targeting of known metastatic sites
      in >90% of patients and those with stronger PSMA expression by semi-quantitative
      imaging had more PSA declines. These clinical studies clearly documented the
      potential therapeutic value of radioimmunotherapy (RIT) in metastatic PCa. 

PMID- 25771366
TI  - Lutetium-177 Labeled Bombesin Peptides for Radionuclide Therapy.
AB  - The rare-earth radionuclides that decay by beta particle (beta-) emission are
      considered to be ideal in the context of targeted radiotherapy. The rare-earth
      isotopes exist primarily in the 3+ oxidation state and are considered to be hard
      metal centers, requiring multidentate, hard donor ligands such as the
      poly(aminocarboxylates) for in vivo kinetic inertness. 177Lu is a rare-earth
      radionuclide that is produced in moderate specific activity (740 GBq/mg) by
      direct neutron capture of enriched 176Lu via the 176Lu(n,gamma)177Lu nuclear
      reaction. 177Lu has a half-life of 6.71 d, decays by beta emission (Ebmax = 0.497
      MeV), and emits two imagable photons (113keV, 3% and 208kev, 11%). High specific
      activity, no-carrier-added 177Lu can also be prepared by an indirect neutron
      capture nuclear reaction on a 176Yb target. Herein, we report upon bombesin (BBN)
      peptides radiolabeled with 177Lu. The impetus driving many of the research
      studies that we have described in this review is that the high-affinity gastrin
      releasing peptide receptor (GRPR, BBN receptor subtype 2, BB2) has been
      identified in tissue biopsy samples and immortalized cell lines of many human
      cancers and is an ideal biomarker for targeting early-stage disease. Early on,
      the ability of GRPR agonists to be rapidly internalized coupled with a high
      incidence of GRPR expression on various neoplasias was a driving force for the
      design and development of new diagnostic and therapeutic agents targeting GRP
      receptor-positive tumors. Recent reports, however, show compelling evidence that
      radiopharmaceutical design and development based upon antagonist-type ligand
      frameworks clearly bears reexamination. Last of all, the ability to target
      multiple biomarkers simultaneously via a heterodimeric targeting ligand has also
      provided a new avenue to investigate the dual targeting capacity of bivalent
      radioligands for improved in vivo molecular imaging and treatment of specific
      human cancers. In this report, we describe recent advances in 177Lu-labeled
      bombesin peptides for targeted radiotherapy that includes agonist, antagonist,
      and multivalent cell-targeting agents. In vitro, in vivo translational, and in
      vivo human clinical investigations are described. 

PMID- 25771367
TI  - 177Lu-Labeled Agents for Neuroendocrine Tumor Therapy and Bone Pain Palliation in
      Uruguay.
AB  - Lutetium-177 is an emerging radionuclide due its convenient chemical and nuclear
      properties. In this paper we describe the development and evaluation in Uruguay
      of the targeted 177Lu labelled radiopharmaceuticals EDTMP (for bone pain
      palliation) and DOTA-TATE (neuroendocrine tumors). We optimized the preparation
      of these 177Lu radiopharmaceuticals including radiolabelling, quality control
      methods, in vitro and in vivo stability and their therapeutic application in
      patients. Radiation dosimetry aspects of 177Lu are also included. Nine male
      patients with prostate cancer and four female patients with breast carcinoma with
      multiple bone metastatic lesions were treated with 177Lu-EDTMP. Four patients
      with gastroentheropancreatic neuroendocrine tumors (GEP-NET) and one patient with
      bronchial NET were treated with 1- 3 cycles with a cumulative dose of 4.44-22.2
      GBq of 177Lu-DOTA-TATE. Scintigraphic images of the patients treated with 177Lu
      EDTMP evidenced high and rapid uptake in bone metastasis, remaining after 7 days
      post administration. Images allow skeletal visualization with high definition and
      demonstrate increased uptake in bone metastases. For 177Lu-DOTA-TATE, partial
      remissions were obtained in 4 patients and the remaining patient did not show
      significant progression 3 months after the second cycle. No serious adverse
      effects were registered, even in two patients with confirmed renal disease and
      high risk for renal disease Dosimetry assessments confirm the predictive value of
      the personalized therapy with radiolabelled peptides. We found it is possible to
      accumulate high therapeutic doses in tumours in sequential administrations of
      177Lu-DOTA-TATE, increasing the probability of biological response without
      significant impairment of the renal function in patients with risk factors. These
      results demonstrate the attractive therapeutic properties of these two 177Lu
      labelled agents and the feasibility of this metabolic therapy in regions far away
      from 177Lu producing countries.

PMID- 25771368
TI  - Lutetium-177 Labeled Peptides: The European Institute of Oncology Experience.
AB  - Peptide receptor radionuclide therapy (PRRT) using radiolabeled somatostatin
      analogues has shown encouraging results in various somatostatin receptor positive
      tumors. Partial remission rates up to 30% have been documented as well as
      significant improvements in quality of life and survival. This treatment takes
      advantage of the high specific binding of the radiolabeled peptide to
      somatostatin receptors overexpressed by the tumors thus being more effective on
      the tumor cells with less systemic side-effects. The development of macrocyclic
      chelators conjugated to peptides made possible the stable binding with various
      radionuclides. In particular 177Lu features favourable physical characteristics
      with a half-life of 6.7 days, emission of beta- with energy of 0.5 MeV for
      treatment and gamma-emissions suitable for imaging. The present contribution
      describes the learning process achieved at the European Institute of Oncology
      (IEO) since the first application of 90Y labeled peptides to the therapy of
      neuroendocrine tumors back in 1997. Continuous improvements led to the
      preparation of a safe 177Lu labeled peptide for human use. Our learning curve
      began with the identification of the optimal characteristics of the isotope
      paying attention to its chemical purity and specific activity along with the
      optimization of the parameters involved in the radiolabeling procedure. Also the
      radiation protection issues have been improved along the years and recently more
      and more attention has been devoted to the pharmaceutical aspects involved in the
      preparation. The overall issue of the quality has now been completed by drafting
      an extensive documentation with the goal to deliver a safe and reliable product
      to our patients. 

PMID- 25771369
TI  - Overview of Development and Formulation of 177Lu-DOTA-TATE for PRRT.
AB  - Peptide receptor radionuclide therapy (PRRT) using radiolabeled somatostatin
      analogs has become an established procedure for the treatment of patients
      suffering from inoperable neuroendocrine cancers over-expressing somatostatin
      receptors. Success of PRRT depends on the availability of the radiolabeled
      peptide with adequately high specific activity, so that required therapeutic
      efficacy can be achieved without saturating the limited number of receptors
      available on the target lesions. Specific activity of the radionuclide and the
      radiolabeled somatostatin analog are therefore an important parameters. Although
      these analogs have been investigated and improved, and successfully applied for
      PRRT for more than 15 years, there are still many possibilities for further
      improvements that fully exploit PRRT with 177Lu-DOTA-TATE. The here summarized
      data presented herein on increased knowledge of the components of 177Lu-DOTA-TATE
      (especially the purity of 177Lu and specific activity of 177Lu) and the reaction
      kinetics during labeling 177Lu-DOTA-TATE clearly show that the peptide dose and
      dose in GBq can be varied. Here we present an overview of the development,
      formulation and optimisation of 177Lu-DOTA-TATE, mainly addressing radiochemical
      parameters. 

PMID- 25771370
TI  - Accurate assessment of whole-body retention for PRRT with (177)Lu using paired
      measurements with external detectors.
AB  - The aim of this study was to assess the accuracy of the results of whole-body
      measurements by comparison with the urine collection method in the PRRT with
      (177)Lu and furthermore to develop a more accurate method of paired measurements.
      Excreted samples were collected at given intervals and activities were measured
      by a dose calibrator. Traditionally, whole-body activities during subsequent
      measurements are normalized individually to the administered activity. In order
      to correct for the effects of the activity in the bladder during the baseline
      measurement before the first voiding and activity redistributions in the patient
      body during subsequent measurements, a series of paired measurements before and
      after each voiding were carried out. Time-dependent detector responses at given
      times were derived and time-activity retentions were then determined. Compared to
      the results of the urine collection, whole-body activities by traditional whole
      body measurements were overestimated by ca. 14% at 1 h after administration and
      randomly varied from -29% to 49% at 24 h. Measurement uncertainties of whole-body
      activities were from +/- 4% (the coverage factor k=2) at 1 h to >+/- 20% at 24 h
      by the urine collection and +/- 7% by paired measurements, respectively. Whole
      body activities at 1 h by paired measurements were validated using the results by
      measurements of the collected first urine. The new method of paired measurements
      has an equivalent measurement accuracy and even better during the later
      measurements with respect to the urine collection method and therefore can
      replace urine approach for assessing the time-activity remaining in the patient
      body.

PMID- 25771371
TI  - Pharmacokinetic, Dosimetry and Toxicity Study of 177Lu-EDTMP in Patients: Phase
      0/I study.
AB  - 177Lu-EDTMP has been proposed as a potent bone pain palliation agent owing to
      theoretical advantage of reduced bone marrow suppression resulting from the low
      beta(-) energy and a suitably long half-life facilitating its wider distribution
      with less loss from radioactive decay. Herein, we report the pharmacokinetics,
      dosimetry and toxicity analysis of 177Lu-EDTMP in patients (phase-0/I study). In
      a phase-0 study, the biokinetics of skeletal and non-skeletal uptake of 177Lu
      EDTMP was assessed in 6 patients with metastatic prostate cancer using tracer
      doses (172.7-206.9MBq). Data of whole skeletal uptake, blood and fractionated
      urine samples were obtained and dosimetric calculations were performed using the
      OLINDA/EXM 1.0 software. Prolonged bone retention was observed in all patients.
      Excretion was mainly via the renal route and blood clearance was rapid and
      biphasic. Mean estimated red marrow dose was 0.80+/-0.15mGy/MBq while mean total
      body dose was 0.16+/-0.04mGy/MBq. A maximum tolerated dose (MTD) of 2000
      3250MBqfor 177Lu-EDTMP was calculated. For the phase-I study, 21 patients with
      metastatic prostate cancer were given a therapeutic dose of 177Lu- EDTMP (692
      5550MBq). Toxiciy (WHO), evaluated by assessment of hemoglobin levels, platelet
      and leukocyte counts over 12 weeks, was mainly limited to anemia or
      thrombocytopenia. Only transient toxicity was observed in 14/21 patients, of
      which 6 had baseline toxicity. Beyond the MTD, a significantly higher number of
      patients displayed grade 3-4 toxicity. Pain relief, assessed by VAS pain score,
      was observed in 86% patients with median relief duration of 7 weeks. The results
      demonstrate that 177Lu-EDTMP has excellent pharmacokinetic and dosimetric
      properties, besides being safe and effective. Along with estimating radiation
      dose values to certain critical organs, we have also proposed an MTD for 177Lu
      EDTMP that correlated well with toxicity data. The encouraging dosimetry and
      toxicity data of 177Lu-EDTMP reported provide the basis for subsequent phases of
      the studies to establish complete effectiveness and safety of 177Lu-EDTMP as an
      attractive alternative to other radioactive bone pain palliation agents.

PMID- 25771372
TI  - Radiation Dosimetry Aspects of (177)Lu.
AB  - This review mainly focuses on the dosimetry methodology which includes
      consideration of the number and time points of scans, imaging methodology,
      methods for integrating time-activity curves and calculating absorbed doses.
      (177)Lu-labelled compounds show many advantages for dosimetry assessments due to
      attractive physical properties which comprise low abundance of photons for
      sufficient post-therapy imaging, a clearly separated gamma peak at 208 keV, and a
      low range of beta particles. The most up-to-date results of absorbed dose
      calculations for the kidneys, bone marrow, and tumors are provided. The absorbed
      doses reported for radiopeptide therapies using (177)Lu labelled compounds taken
      from clinical studies show a high variability, presumably because of the
      different applied methodologies. 

PMID- 25771373
TI  - Development and biological studies of 177Lu-DOTA-rituximab for the treatment of
      Non-Hodgkin's lymphoma.
AB  - The optimization of DOTA-NHS-ester conjugation to Rituximab using different
      Ab:DOTA molar ratios (1:10, 1:20, 1:50 and 1:100) was studied. High radiochemical
      yield, in vitro stability and immunoreactive fraction were obtained for the
      Rituximab conjugated at 1:50 molar ratio, resulting in the incorporation of an
      average number of 4.9 +/- 1.1 DOTA per Rituximab molecule. Labeling with 177Lu
      was performed in high specific activity with great in vitro stability.
      Biodistribution in healthy and xenographed mice showed tumor uptake and high in
      vivo stability as evidenced by low uptake in bone. The properties of 177Lu-DOTA
      Rituximab prepared from DOTA-NHS-ester suggest the potential for the application
      of the 177Lu-labeled antibody in preliminary clinical studies. 

PMID- 25771374
TI  - Evaluation of 177Lu-EDTMP in Dogs with Spontaneous Tumor Involving Bone:
      Pharmacokinetics, Dosimetry and Therapeutic Efficacy.
AB  - 177Lu-EDTMP is currently being investigated as a potential agent for providing
      palliative care to the patients suffering from bone pain due to metastatic
      skeletal carcinoma. The present article describes the evaluation of 177Lu-EDTMP
      complex in four different canine patients with different types of primary and
      metastatic skeletal lesions with respect to its pharmacokinetic properties,
      dosimetry and therapeutic efficacy. The dogs were treated with a dose of ~44.4
      MBq (1.2 mCi) per kg body weight of 177Lu-EDTMP, synthesized in-house with high
      radiochemical purity (98.8 +/- 0.4 %) and excellent in vitro stability. The
      radiopharmaceutical showed favourable pharmacokinetic properties, such as,
      preferential accumulation at skeletal lesion sites and fast clearance from blood
      and other non-target organs through urinary route. The administered dose of the
      radiopharmacutical showed excellent therapeutic efficacy in case of a dog
      suffering from skeletal metastasis originating from primary tumor elsewhere. On
      the other hand, two of the remaining three patients with primary bone cancer
      showed stable disease intially with palliative effect. The fourth patient having
      metal implant induced osteosarcoma with severe limb oedema did not show any
      response to the treatment. 

PMID- 25771375
TI  - Estimation of specific activity of 177Lu by 'saturation assay' principle using
      DOTA as ligand.
AB  - Lutetium-177 is a widely used therapeutic radionuclide in targeted therapy and it
      is important to know its specific activity at the time of radiopharmaceutical
      preparation, especially for radiolabeling peptides. However, there are no direct
      methods for the experimental determination of the specific activity which can be
      readily applied in a hospital radiopharmacy. A new technique based on the
      'saturation assay' principle using DOTA as the binding agent for the estimation
      of specific activity of (177)Lu is reported. The studies demonstrate the proof of
      principle of this new assay technique. The method is general and can be modified
      and applied for the estimation of specific activity of other metallic
      radionuclides by using DOTA or other suitable chelating agents. 

PMID- 25771376
TI  - Alternative method to determine Specific Activity of (177)Lu by HPLC.
AB  - Peptide Receptor Radionuclide Therapy (PRRT) with (177)Lu-DOTA-peptides requires
      (177)Lu with high specific activity (SA) and values >740 GBq (177)Lu per mg Lu to
      maximise the atom% of (177)Lu over total Lu. Vendors provide SA values which are
      based on activity and mass of the target, whereas due to "burn-up" of target,
      these SA values are not accurate. For a radiochemist the SA of (177)Lu is of
      interest prior to radiolabeling. An alternative method to determine SA was
      developed by HPLC, which includes a metal titration of a known amount of DOTA
      peptide with a known amount of activity ((177)Lu), and a unknown amount of metal
      ((177+nat)Lu). Based on an HPLC separation of radiometal-DOTA-peptide and DOTA
      peptide, and the concordant ratio of these components the metal content
      ((177+nat)Lu) can be calculated, and eventually the SA of (177)Lu can be
      accurately determined. These experimentally determined SA values exceeded the
      estimated values provided by vendors by 27 +/- 16%, (range 6-73 %). The deviation
      of SA values for samples from the same Lu batch was <2% (n >= 10). IN CONCLUSION:
      the SA of (177)Lu is apparently often higher as stated by vendors in comparison
      to the experimentally determined actual values. For this reason, the SA of
      (177)Lu-DOTA-TATE and other Lu-DOTA-peptides could be increased accordingly.

PMID- 25771377
TI  - Indirect Production of No Carrier Added (NCA) (177)Lu from Irradiation of
      Enriched (176)Yb: Options for Ytterbium/Lutetium Separation.
AB  - This article presents a concise review of the production of no-carrier-added
      (NCA) (177)Lu by the 'indirect' route by irradiating ytterbium-176 ((176)Yb)
      enriched targets. The success of this production method depends on the ability to
      separate the microscopic amounts of NCA (177)Lu from bulk irradiated ytterbium
      targets. The presence of Yb(+3) from the target in the final processed (177)Lu
      will adversely affect the quality of (177)Lu by decreasing the specific activity
      and competing with Lu(+3) complexation since ytterbium will follow the same
      coordination chemistry. Ytterbium and lutetium are adjacent members of the
      lanthanide family with very similar chemical properties which makes the
      separation of one from the other a challenging task. This review provides a
      summary of the methods developed for the separation and purification of NCA
      (177)Lu from neutron irradiated (176)Yb-enriched targets, a critical assessment
      of recent developments and a discussion of the current status of this (177)Lu
      production method. 

PMID- 25771378
TI  - Production of No-Carrier Added Lutetium-177 by Irradiation of Enriched Ytterbium
      176.
AB  - Two methods of Lu-177 production are reviewed: irradiation of isotopically
      enriched Lu- 176 (direct way) and irradiation of ytterbium enriched with Yb-176
      (indirect way). Based on neutronphysical calculations Lu-177 yield and specific
      activity were estimated for both methods. Lu-177 specific activity strongly
      depends on neutron flux density in the direct way, that is 75,000 Ci/g for 10-
      days irradiation in a neutron flux of 2.10(15) cm(-2) s(-1), and only 13,000 Ci/g
      after 30 days irradiation at neutron flux 1.10(14) cm(-2) s(-1). Irradiation of
      Yb-176 provides Lu-177 specific activity close to theoretical value (110,000
      Ci/g). Neutron flux density effect Lu-177 yield, that is 530 Ci/g for 2.1015 cm(
      2) s(-1) neutron flux density after 30 days irradiation. A procedure of isolation
      and purification of Lu-177 from irradiated targets is described based on
      combination of galvanostatic extraction of ytterbium followed by cation-exchange
      chromatography from alfa-hydroxyisobutirate solutions on BioRad AG((r))50W-X8
      resin.

PMID- 25771379
TI  - Chemistry and bifunctional chelating agents for binding (177)Lu.
AB  - A short overview of fundamental chemistry of lutetium and of structural
      characteristics of lutetium coordination complexes, as relevant for understanding
      the properties of lutetium-177 radiopharmaceuticals, is presented. This includes
      basic concepts on lutetium electronic structure, lanthanide contraction,
      coordination geometries, behavior in aqueous solution and thermodynamic
      stability. An illustration of the structure and binding properties of the most
      important chelating agents for the Lu(3+) ion in aqueous solution is also
      reported with specific focus on coordination complexes formed with linear and
      macrocyclic polydentate amino-carboxylate donor ligands. 

PMID- 25771380
TI  - Evolving Important Role of Lutetium-177 for Therapeutic Nuclear Medicine.
AB  - Lutetium-177 ((177)Lu) is a late entrant into the nuclear medicine therapy arena
      but is expected to become one of the most widely used therapeutic radionuclides.
      This paper analyses the reason for the increasing preference of (177)Lu as a
      therapeutic radionuclide. While the radionuclidic properties favor its use for
      several therapeutic applications, the potential for large scale production of
      (177)Lu is also an important aspect for its acceptability as a therapeutic
      radionuclide. This introductory discussion also summarizes some developing
      clinical uses and suggested future directions for applications of (177)Lu. 

PMID- 25771381
TI  - Editorial: Lutetium-177 Labeled Therapeutics: Emerging Importance for Cancer
      Treatment and Therapy of Chronic Disease.

PMID- 25771383
TI  - Picosecond time-resolved fluorescent spectroscopy of 1-anilino-8-naphthalene
      sulfonate binding with staphylococcal nuclease in the native and molten globule
      states.
AB  - We studied the picosecond time-resolved fluorescent spectroscopy of 1-anilino-8
      naphthalene sulfonate (ANS), which binds to the staphylococcal nuclease (SNase)
      of the wild-type (WT) and the molten globule (MG) state. Three ANS emission bands
      at ~530nm, ~495nm, and ~475nm are resolved, corresponding to three ANS states:
      the free ANS in solution and associated form adsorbing to surface sites and
      binding to active sites. The surface hydrophobicity of the WT is moderate and
      different from the MG state, as shown both in the position of the bands and by
      the concentration dependent ANS fluorescent decay. For MG, the decay of two blue
      bands accelerated with the increment of the ANS concentration, whereas the WT did
      not show this dependency. However, when pdTp, an inhibitor, was attached to the
      active site of the MG state, band 2 decay was also independent of the ANS
      concentration. These results indicate that the protein hydrophobic sites have two
      types of interactions with ANS. 

PMID- 25771382
TI  - Synthesis, spectroscopic, and in vitro investigations of 2,6-diiodo-BODIPYs with
      PDT and bioimaging applications.
AB  - A series of five mono-styryl and their corresponding symmetric di-styryl-2,6
      diiodo-BODIPYs containing indolyl, pyrrolyl, thienyl or tri(ethylene
      glycol)phenyl groups were synthesized using Knoevenagel condensations. The yields
      for the condensation reactions were improved up to 40% using microwave
      irradiation (90 degrees C for 1h at 400W) due to lower decomposition of BODIPYs
      upon prolonged heating. The spectroscopic, structural (including the X-ray of a
      di-styryl-2,6-diiodo-BODIPY) and in vitro properties of the BODIPYs were
      investigated. The extension of pi-conjugation through the 3,5-dimethyls of the
      known phototoxic 2,6-diiodo-BODIPY 1 produced bathochromic shifts in the
      absorption and emission spectra, in the order of 63-125nm for the mono-styryl-
      and 128-220nm for the di-styryl-BODIPYs in DMSO. The largest red-shifts were
      observed for the indolyl-containing BODIPYs while the largest fluorescence
      quantum yields were observed for the tri(ethyleneglycol)phenylstyryl-BODIPYs.
      Among this series, only the mono-styryl-BODIPYs were phototoxic (IC50=2-15MUM at
      1.5J/cm(2)), and were observed to localize preferentially in the cell ER and
      mitochondria. On the other hand, the di-styryl-BODIPYs were found to have low or
      no phototoxicity (IC50>100MUM at 1.5J/cm(2)). Among this series of compounds
      BODIPY 2a shows the most promise for application as photosensitizer in PDT. 

PMID- 25771384
TI  - Oxidatively damaged DNA in the nasal epithelium of workers occupationally exposed
      to silica dust in Tuscany region, Italy.
AB  - Chronic silica exposure has been associated to cancer and silicosis. Furthermore,
      the induction of oxidative stress and the generation of reactive oxygen species
      have been indicated to play a main role in the carcinogenicity of respirable
      silica. Therefore, we conducted a cross-sectional study to evaluate the
      prevalence of 3-(2-deoxy-beta-D-erythro-pentafuranosyl)pyrimido[1,2-alpha]purin
      10(3H)-one deoxyguanosine (M1dG) adducts, a biomarker of oxidative stress and
      peroxidation of lipids, in the nasal epithelium of 135 silica-exposed workers,
      employed in pottery, ceramic and marble manufacturing plants as well as in a
      stone quarry, in respect to 118 controls living in Tuscany region, Italy. The
      M1dG generation was measured by the (32)P-postlabelling assay. Significant higher
      levels of M1dG adducts per 10(8) normal nucleotides were observed in the nasal
      epithelium of smokers, 77.9+/-9.8 (SE), and in those of former smokers, 80.7+/
      9.7 (SE), as compared to non-smokers, 57.1+/-6.2 (SE), P = 0.001 and P = 0.004,
      respectively. Significant increments of M1dG adducts were found in the nasal
      epithelium of workers that handle artificial marble conglomerates, 184+/-36.4
      (SE), and in those of quarry workers, 120+/-34.7 (SE), with respect to controls,
      50.6+/-2.7 (SE), P = 0.014 and P < 0.001, respectively. Null increments were
      observed in association with the pottery and the ceramic factories. After
      stratification for different exposures, silica-exposed workers that were co
      exposed to organic solvents, and welding and exhaust fumes have significantly
      higher M1dG levels, 90.4+/-13.4 (SE), P = 0.014 vs. CONTROL: Our data suggested
      that silica exposure might be associated with genotoxicity in the nasal
      epithelial cells of silica-exposed workers that handle of artificial marble
      conglomerates and quarry workers. Importantly, we observed that co-exposures to
      other respiratory carcinogens may have contributed to enhance the burden of M1dG
      adducts in the nasal epithelium of silica-exposed workers.

PMID- 25771385
TI  - DNA strand breaks, acute phase response and inflammation following pulmonary
      exposure by instillation to the diesel exhaust particle NIST1650b in mice.
AB  - We investigated the inflammatory response, acute phase response and genotoxic
      effect of diesel exhaust particles (DEPs, NIST1650b) following a single
      intratracheal instillation. C57BL/6J BomTac mice received 18, 54 or 162 ug/mouse
      and were killed 1, 3 and 28 days post-exposure. Vehicle controls and the
      benchmark particle carbon black (CB, Printex 90; 162 ug/mouse) were tested
      alongside for comparison. The cellular composition and protein concentration were
      determined in bronchoalveolar lavage (BAL) fluid as markers for an inflammatory
      response. Pulmonary and systemic genotoxicity was analysed by the alkaline comet
      assay as DNA strand breaks in BAL cells, lung and liver tissue. The pulmonary
      acute phase response was analysed by Saa3 mRNA levels by real-time quantitative
      polymerase chain reaction. Instillation of DEP induced a strong neutrophil influx
      1 and 3 days, but not 28 days post-exposure. Saa3 mRNA levels were increased at
      all time point for the highest dose and 28 days post-exposure for the middle
      dose. DEP increased levels of DNA strand breaks in lung tissue for all doses 1
      day post-exposure and after 28 days for mid- and high-dose groups. Pulmonary
      exposure to DEP induced transient inflammation but long-lasting pulmonary acute
      phase response as well as genotoxicity in lung tissue 28 days post-exposure. The
      observed long-term pulmonary genotoxicity by DEP was less than the previously
      observed genotoxicity for CB using identical experimental set-up. 

PMID- 25771387
TI  - Treatment of asthma based on symptoms.

PMID- 25771386
TI  - Variants in Solute Carrier SLC26A9 Modify Prenatal Exocrine Pancreatic Damage in
      Cystic Fibrosis.
AB  - OBJECTIVES: To test the hypothesis that multiple constituents of the apical
      plasma membrane residing alongside the causal cystic fibrosis (CF) transmembrane
      conductance regulator protein, including known CF modifiers SLC26A9, SLC6A14, and
      SLC9A3, would be associated with prenatal exocrine pancreatic damage as measured
      by newborn screened (NBS) immunoreactive trypsinogen (IRT) levels. STUDY DESIGN:
      NBS IRT measures and genome-wide genotype data were available on 111 subjects
      from Colorado, 37 subjects from Wisconsin, and 80 subjects from France. Multiple
      linear regression was used to determine whether any of 8 single nucleotide
      polymorphisms (SNPs) in SLC26A9, SLC6A14, and SLC9A3 were associated with IRT and
      whether other constituents of the apical plasma membrane contributed to IRT.
      RESULTS: In the Colorado sample, 3 SLC26A9 SNPs were associated with NBS IRT (min
      P=1.16*10(-3); rs7512462), but no SLC6A14 or SLC9A3 SNPs were associated (P>.05).
      The rs7512462 association replicated in the Wisconsin sample (P=.03) but not in
      the French sample (P=.76). Furthermore, rs7512462 was the top-ranked apical
      membrane constituent in the combined Colorado and Wisconsin sample. CONCLUSIONS:
      NBS IRT is a biomarker of prenatal exocrine pancreatic disease in patients with
      CF, and a SNP in SLC26A9 accounts for significant IRT variability. This work
      suggests SLC26A9 as a potential therapeutic target to ameliorate exocrine
      pancreatic disease.

PMID- 25771388
TI  - Omega-3 Fatty acids therapy in children with nonalcoholic Fatty liver disease: a
      randomized controlled trial.
AB  - OBJECTIVE: To evaluate the efficacy and safety of omega-3 fatty acid
      supplementation in children with nonalcoholic fatty liver disease (NAFLD). STUDY
      DESIGN: Overweight/obese children with NAFLD (n = 76; median age, 13 years; IQR,
      11.1-15.2 years) were eligible to participate in the study. The diagnosis of
      NAFLD was based on elevated alanine aminotransferase (ALT) to >= 30% of the upper
      limit of normal (ULN) and liver hyperechogenicity on ultrasound. Patients were
      randomized to receive omega-3 fatty acids (docosahexaenoic acid and
      eicosapentaenoic acid, 450-1300 mg/day) or placebo (omega-6 sunflower oil). The
      primary outcome was the number of patients who demonstrated decreased ALT
      activity by >= 0.3 times the ULN. Secondary outcomes included alterations in
      liver function tests, liver hyperechogenicity, insulin resistance, and other
      metabolic markers after 6 months of intervention. RESULTS: Out of 76 enrolled
      patients, 64 completed the trial and were analyzed. After 6 months, we found no
      significant differences between the omega-3 and placebo groups in the number of
      patients with decreased ALT by >= 0.3 times the ULN (24 vs 23) or in median (IQR)
      ALT activity (48.5 [31-62] U/L vs 39 [27-55] U/L), liver hyperechogenicity,
      insulin resistance, or serum lipid levels. However, patients in the omega-3 group
      had lower levels of aspartate aminotransferase (28 [25-36] U/L vs 39 [27-55] U/L;
      P = .04) and gamma-glutamyl transpeptidase (26 [17.5-36.5] U/L vs 35 [22-52] U/L;
      P = .04), and significantly higher levels of adiponectin. CONCLUSION: Omega-3
      fatty acid supplementation did not increase the number of patients with decreased
      ALT levels and it did not affect liver steatosis on ultrasound, but it improved
      aspartate aminotransferase and gamma-glutamyl transpeptidase levels in children
      with NAFLD compared with placebo. TRIAL REGISTRATION: Registered with
      ClinicalTrials.gov: NCT01547910.

PMID- 25771390
TI  - Anthropometric indices and metabolic co-morbidities.

PMID- 25771389
TI  - Treatment of methylmalonic acidemia by liver or combined liver-kidney
      transplantation.
AB  - OBJECTIVE: To assess biochemical, surgical, and long-term outcomes of liver (LT)
      or liver-kidney transplantation (LKT) for severe, early-onset methylmalonic
      acidemia/acid (MMA). STUDY DESIGN: A retrospective chart review (December 1997 to
      May 2012) of patients with MMA who underwent LT or LKT at Lucile Packard
      Children's Hospital at Stanford. RESULTS: Fourteen patients underwent LT (n = 6)
      or LKT (n = 8) at mean age 8.2 years (range 0.8-20.7). Eleven (79%) were
      diagnosed during the neonatal period, including 6 by newborn screening. All
      underwent deceased donor transplantation; 12 (86%) received a whole liver graft.
      Postoperative survival was 100%. At a mean follow-up of 3.25 +/- 4.2 years,
      patient survival was 100%, liver allograft survival 93%, and kidney allograft
      survival 100%. One patient underwent liver re-transplantation because of hepatic
      artery thrombosis. After transplantation, there were no episodes of
      hyperammonemia, acidosis, or metabolic decompensation. The mean serum MMA at the
      time of transplantation was 1648 +/- 1492 MUmol/L (normal <0.3, range 99-4420).
      By 3 days, post-transplantation levels fell on average by 87% (mean 210 +/- 154
      MUmol/L), and at 4 months, they were 83% below pre-transplantation levels (mean
      305 +/- 108 MUmol/L). Developmental delay was present in 12 patients (86%) before
      transplantation. All patients maintained neurodevelopmental abilities or
      exhibited improvements in motor skills, learning abilities, and social
      functioning. CONCLUSIONS: LT or LKT for MMA eradicates episodes of
      hyperammonemia, results in excellent long-term survival, and suggests
      stabilization of neurocognitive development. Long-term follow-up is underway to
      evaluate whether patients who undergo early LT need kidney transplantation later
      in life.

PMID- 25771391
TI  - Diagnosis of systemic-onset juvenile idiopathic arthritis after treatment for
      presumed Kawasaki disease.
AB  - OBJECTIVES: To estimate the incidence of systemic-onset juvenile idiopathic
      arthritis (SoJIA) within 6 months after treatment for presumed Kawasaki disease
      (KD) (presumed patients with KD with subsequent diagnosis of SoJIA [pKD/SoJIA])
      and describe presentation differences from sole KD. STUDY DESIGN: We identified
      patients treated for KD at Nationwide Children's Hospital and from the Pediatric
      Health Information System from 2009-2013. We then identified the subset of
      children, pKD/SoJIA, who received an International Classification of Diseases,
      Ninth Revision code for SoJIA and had it listed at least once 3 months after and
      within 6 months after KD diagnosis. Demographic characteristics, readmission
      rates, treatments, and complications were noted. A literature review was also
      performed to identify clinical, laboratory, and echocardiographic data of
      previously documented patients with KD later diagnosed with SoJIA. RESULTS: There
      were 6745 total treated patients with KD in the Pediatric Health Information
      System database during the study period; 10 patients were identified to have
      pKD/SoJIA (0.2% of cohort). Those with pKD/SoJIA were predominantly Caucasian
      compared with patients with KD (90% and 46.8%, respectively; P=.003). Macrophage
      activation syndrome was more common in patients with pKD/SoJIA than in sole
      patients with KD (30% and 0.30%, respectively; P<.001). Fifteen cases of
      pKD/SoJIA were identified by literature and chart review, 12 of whom were
      initially diagnosed with incomplete KD. CONCLUSIONS: We reported a 0.2% incidence
      of pKD/SoJIA, which was associated with Caucasian race, macrophage activation
      syndrome, and an incomplete KD phenotype.

PMID- 25771392
TI  - Normal-appearing cerebral white matter in healthy adults: mean change over 2
      years and individual differences in change.
AB  - Diffusion tensor imaging studies show age-related differences in cerebral white
      matter (WM). However, few have studied WM changes over time, and none evaluated
      individual differences in change across a wide age range. Here, we examined 2
      year WM change in 96 healthy adults (baseline age, 19-78 years), individual
      differences in change, and the influence of vascular and metabolic risk thereon.
      Fractional anisotropy (FA), axial diffusivity, and radial diffusivity (RD)
      represented microstructural properties of normal-appearing WM within 13 regions.
      Cross-sectional analyses revealed age-related differences in all WM indices
      across the regions. In contrast, latent change score analyses showed longitudinal
      declines in axial diffusivity in association and projection fibers and increases
      in anterior commissural fibers. FA and RD evidenced a less consistent pattern of
      change. Metabolic risk mediated the effects of age on FA and RD change in corpus
      callosum body and dorsal cingulum. These findings underscore the importance of
      longitudinal studies in evaluating individual differences in change and the role
      of metabolic factors in shaping trajectories of brain aging. 

PMID- 25771393
TI  - d-Aspartate oxidase influences glutamatergic system homeostasis in mammalian
      brain.
AB  - We have investigated the relevance of d-aspartate oxidase, the only enzyme known
      to selectively degrade d-aspartate (d-Asp), in modulating glutamatergic system
      homeostasis. Interestingly, the lack of the Ddo gene, by raising d-Asp content,
      induces a substantial increase in extracellular glutamate (Glu) levels in Ddo
      mutant brains. Consistent with an exaggerated and persistent N-methyl-d-aspartate
      receptor (NMDAR) stimulation, we documented in Ddo knockouts severe age-dependent
      structural and functional alterations mirrored by expression of active caspases 3
      and 7 along with appearance of dystrophic microglia and reactive astrocytes. In
      addition, prolonged elevation of d-Asp triggered in mutants alterations of NMDAR
      dependent synaptic plasticity associated to reduction of hippocampal GluN1 and
      GluN2B subunits selectively located at synaptic sites and to increase in the
      alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid-to-N-methyl-d-aspartate
      ratio. These effects, all of which converged on a progressive hyporesponsiveness
      at NMDAR sites, functionally resulted in a greater vulnerability to phencyclidine
      induced prepulse inhibition deficits in mutants. In conclusion, our results
      indicate that d-aspartate oxidase, by strictly regulating d-Asp levels, impacts
      on the homeostasis of glutamatergic system, thus preventing accelerated
      neurodegenerative processes. 

PMID- 25771394
TI  - Mutational analysis of MATR3 in Taiwanese patients with amyotrophic lateral
      sclerosis.
AB  - Mutations in the MATR3 gene were just recently identified to cause familial
      amyotrophic lateral sclerosis, and their role in amyotrophic lateral sclerosis
      (ALS) in various populations remains unclear. The aim of this study was to
      determine the frequency and spectrum of mutations in MATR3 in a Taiwanese ALS
      cohort of Han Chinese origin. Mutational analyses of MATR3 were carried out by
      direct nucleotide sequencing in a cohort of 207 unrelated patients with ALS.
      Among them, the genetic diagnoses of 169 patients remained elusive after
      mutations in SOD1, C9ORF72, TARDBP, FUS, ATXN2, OPTN, VCP, UBQLN2, SQSTM1, PFN1,
      HNRNPA1, and HNRNPA2B1 had been excluded. We identified 1 heterozygous missense
      mutation, p.Ala72Thr (c.214G>A), in 1 patient with bulbar-onset and apparently
      sporadic ALS. The frequency of MATR3 mutations in ALS patients in Taiwan is,
      therefore, approximately 0.5% (1 of 207). This study reports a novel MATR3
      mutation and stresses on the importance to consider MATR3 mutation as a possible
      etiology of ALS. 

PMID- 25771396
TI  - Silibinin inhibits acetylcholinesterase activity and amyloid beta peptide
      aggregation: a dual-target drug for the treatment of Alzheimer's disease.
AB  - Alzheimer's disease (AD) is characterized by amyloid beta (Abeta) peptide
      aggregation and cholinergic neurodegeneration. Therefore, in this paper, we
      examined silibinin, a flavonoid extracted from Silybum marianum, to determine its
      potential as a dual inhibitor of acetylcholinesterase (AChE) and Abeta peptide
      aggregation for AD treatment. To achieve this, we used molecular docking and
      molecular dynamics simulations to examine the affinity of silibinin with Abeta
      and AChE in silico. Next, we used circular dichroism and transmission electron
      microscopy to study the anti-Abeta aggregation capability of silibinin in vitro.
      Moreover, a Morris Water Maze test, enzyme-linked immunosorbent assay,
      immunohistochemistry, 5-bromo-2-deoxyuridine double labeling, and a gene gun
      experiment were performed on silibinin-treated APP/PS1 transgenic mice. In
      molecular dynamics simulations, silibinin interacted with Abeta and AChE to form
      different stable complexes. After the administration of silibinin, AChE activity
      and Abeta aggregations were down-regulated, and the quantity of AChE also
      decreased. In addition, silibinin-treated APP/PS1 transgenic mice had greater
      scores in the Morris Water Maze. Moreover, silibinin could increase the number of
      newly generated microglia, astrocytes, neurons, and neuronal precursor cells.
      Taken together, these data suggest that silibinin could act as a dual inhibitor
      of AChE and Abeta peptide aggregation, therefore suggesting a therapeutic
      strategy for AD treatment. 

PMID- 25771397
TI  - Immune profiling in patients with recurrent miscarriage.
AB  - The central role of the maternal immune system for successful and disturbed
      pregnancies such as recurrent miscarriage (RM) is apparent. Recent studies have
      increased understanding of the complex interaction of the different immunological
      players and the adaptation of the maternal immune system to the semi-allogeneic
      embryo. There is growing evidence for immunological abnormalities in RM patients,
      including autoimmune and allogeneic factors. However, the question remains
      unsolved whether these changes represent the cause or the consequence of RM. As
      in half of the RM patients the underlying mechanism remains unknown, further
      diagnostic methods are urgently needed. Within this review we summarize (recent)
      literature on the immunological diagnosis in RM patients to find out current
      trends and to identify potential targets of therapy. As the exact mechanisms of
      feto-maternal tolerance have not yet been determined we suggest that the
      immunological diagnosis should be implemented only in well-designed clinical
      trials in specialized centers to establish a standardized immunological work-up
      in RM patients. 

PMID- 25771395
TI  - Heat shock protein defenses in the neocortex and allocortex of the telencephalon.
AB  - The telencephalic allocortex develops protein inclusions before the neocortex in
      many age-related proteinopathies. One major defense mechanism against
      proteinopathic stress is the heat shock protein (Hsp) network. We therefore
      contrasted Hsp defenses in stressed primary neocortical and allocortical cells.
      Neocortical neurons were more resistant to the proteasome inhibitor MG132 than
      neurons from 3 allocortical subregions: entorhinal cortex, piriform cortex, and
      hippocampus. However, allocortical neurons exhibited higher MG132-induced
      increases in Hsp70 and heat shock cognate 70 (Hsc70). MG132-treated allocortical
      neurons also exhibited greater levels of protein ubiquitination. Inhibition of
      Hsp70/Hsc70 activity synergistically exacerbated MG132 toxicity in allocortical
      neurons more than neocortical neurons, suggesting that the allocortex is more
      reliant on these Hsp defenses. In contrast, astrocytes harvested from the
      neocortex or allocortex did not differ in their response to Hsp70/Hsc70
      inhibition. Consistent with the idea that chaperones are maximally engaged in
      allocortical neurons, an increase in Hsp70/Hsc70 activity was protective only in
      neocortical neurons. Finally, the levels of select Hsps were altered in the
      neocortex and allocortex in vivo with aging. 

PMID- 25771398
TI  - Decidual cytokines and pregnancy complications: focus on spontaneous miscarriage.
AB  - The establishment of pregnancy requires the co-ordinated implantation of the
      embryo into the receptive decidua, placentation, trophoblast invasion of the
      maternal decidua and myometrium in addition to remodelling of the uterine spiral
      arteries. Failure of any of these steps can lead to a range of pregnancy
      complications, including miscarriage, pre-eclampsia, fetal growth restriction,
      placenta accreta and pre-term birth. Cytokines are small multifunctional proteins
      often derived from leucocytes and have primarily been described through their
      immunomodulatory actions. The maternal-fetal interface is considered to be
      immunosuppressed to allow development of the semi-allogeneic placental fetal
      unit. However, cytokine profiles of the decidua and different decidual cell types
      suggest that the in vivo situation might be more complex. Data suggest that
      decidual-derived cytokines not only play roles in immunosuppression, but also in
      other aspects of the establishment of pregnancy, including the regulation of
      trophoblast invasion and spiral artery remodelling. This review focuses on the
      potential role of decidua-derived cytokines in the aetiology of unexplained
      spontaneous miscarriage. 

PMID- 25771399
TI  - Intraoperative Transrectal Ultrasonography for Hysteroscopic Metroplasty:
      Feasibility and Safety.
AB  - The primary objective of this prospective comparative nonrandomized study was to
      assess the feasibility and safety of intraoperative transrectal ultrasonography
      (TRUS) during hysteroscopic metroplasty (HM). The secondary objective of the
      study was to assess whether TRUS facilitates complete removal of the uterine
      septum. Septate uterus was diagnosed by 3-dimensional transvaginal
      ultrasonography (3D-TVS) and confirmed by magnetic resonance imaging. In the
      control group (HM group; n = 18), patients underwent HM according to the
      traditional standard of operative hysteroscopy. In the study group (HM+TRUS
      group; n = 27), HM and TRUS were performed simultaneously; the hysteroscopic
      procedure was continued until a normal uterine fundus was observed. At 6 to 8
      weeks after HM, 3D-TVS was performed to identify the numbers of complete
      resections (residual septum absent or <5 mm), suboptimal resections (residual
      septum 5-10 mm), and incomplete resections (residual septum > 10 mm). The 2 study
      groups did not differ significantly in terms of demographic and clinical
      characteristics, or in the volume of fluid infused and absorbed. There were no
      severe intraoperative or postoperative complication in either group; 2 patients
      in the HM+TRUS group and 1 patient in the HM group experienced urinary tract
      infection (p = .807). At 6 to 8 weeks after HM, the number of suboptimal
      resections and incomplete resections was higher in the HM group than in the
      HM+TRUS group (p = .031). Residual septum >10 mm (incomplete resection) was seen
      in 1 patient in the HM group but in no patients in the HM+TRUS group.
      Intraoperative TRUS can be performed safely during HM, and may increase the
      likelihood of complete resection of the uterine septum; however, this finding
      should be confirmed by larger studies. 

PMID- 25771400
TI  - Response priming evidence for feedforward processing of snake contours but not of
      ladder contours and textures.
AB  - In contour integration, increased difficulty in detection and shape
      discrimination of a chain of parallel elements (a ladder contour) compared to
      collinear elements (a snake contour) suggests more extensive processing of
      ladders than of snakes. In addition, conceptual similarities between ladders and
      textures - which also involve grouping of parallel elements - raises the question
      whether ladder and texture processing requires feedback from higher visual areas
      while snakes are processed in a fast feedforward sweep. We tested this in a
      response priming paradigm, where participants responded as quickly and accurately
      as possible to the orientation of a diagonal contour in a Gabor array (target).
      The diagonal was defined either by a snake, ladder, texture, or a continuous
      line. The target was preceded with varying stimulus onset asynchrony (SOA) by a
      prime that was either a snake, ladder, or texture, and was consistent or
      inconsistent to the response demands of the target. Resulting priming effects
      clearly distinguished between processing of snakes, ladders, and textures.
      Effects generally increased with SOA but were stronger for snakes and textures
      compared to ladders. Importantly, only priming effects for snakes were fully
      present already in the fastest response times, in accordance with a simple
      feedforward processing model. We conclude that snakes, ladders, and textures do
      not share similar processing characteristics, with snakes exhibiting a pronounced
      processing advantage.

PMID- 25771401
TI  - A population study of binocular function.
AB  - As part of a genome-wide association study (GWAS) of perceptual traits in healthy
      adults, we measured stereo acuity, the duration of alternative percepts in
      binocular rivalry and the extent of dichoptic masking in 1060 participants. We
      present the distributions of the measures, the correlations between measures, and
      their relationships to other psychophysical traits. We report sex differences,
      and correlations with age, interpupillary distance, eye dominance, phorias,
      visual acuity and personality. The GWAS, using data from 988 participants,
      yielded one genetic association that passed a permutation test for significance:
      The variant rs1022907 in the gene VTI1A was associated with self-reported ability
      to see autostereograms. We list a number of other suggestive genetic associations
      (p<10(-5)).

PMID- 25771403
TI  - Re: Disparities in Utilization of Autologous Hematopoietic Cell Transplantation
      for Treatment of Multiple Myeloma.
AB  - Costa et al. recently reported that racial disparities prevented nearly 40% of
      non-Hispanic blacks with multiple myeloma (MM) from undergoing stem cell
      transplantation (SCT), but the authors were unable to provide an explanation for
      the disparities because of limitations of their datasets. They hypothesized that
      socioeconomic status (SES) and/or insurance providers might account for the
      disparity. To examine the issue raised by Costa et al., we performed a secondary
      analysis using hierarchical multivariate logistic regression with data previously
      collected to determine if age at diagnosis, sex, SES, primary insurance provider
      at diagnosis, and comorbidity score help explain the racial disparities in SCT
      utilization. A model of race, age, sex, SES, insurance provider, and comorbidity
      score was the most accurate model in predicting stem cell utilization status
      (chi(2)[12] = 193.859; P < .001; area under the curve = .837; P < .001). After
      controlling for the covariates, black patients were less likely to undergo SCT
      than white patients (adjusted odds ratio, .49; 95% confidence interval, .27 to
      .89; P = .013). In conclusion, we also observed racial disparities between black
      and white patients with MM in SCT utilization and these are not fully accounted
      for by the covariates age, sex, SES, insurance provider, and comorbidity score. 

PMID- 25771402
TI  - Imatinib mesylate for the treatment of steroid-refractory sclerotic-type
      cutaneous chronic graft-versus-host disease.
AB  - Sclerotic skin manifestations of chronic graft-versus-host disease (ScGVHD) lead
      to significant morbidity, including functional disability from joint range of
      motion (ROM) restriction. No superior second-line therapy has been established
      for steroid-refractory disease. Imatinib mesylate is a multikinase inhibitor of
      several signaling pathways implicated in skin fibrosis with in vitro antifibrotic
      activity. We performed an open-label pilot phase II trial of imatinib in children
      and adults with corticosteroid-refractory ScGVHD. Twenty patients were enrolled
      in a 6-month trial. Eight received a standard dose (adult, 400 mg daily;
      children, 260 mg/m(2) daily). Because of poor tolerability, 12 additional
      patients underwent a dose escalation regimen (adult, 100 mg daily initial dose up
      to 200 mg daily maximum; children, initial dose 65 mg/m(2) daily up to 130
      mg/m(2) daily). Fourteen patients were assessable for primary response,
      improvement in joint ROM deficit, at 6 months. Primary outcome criteria for
      partial response was met in 5 of 14 (36%), stable disease in 7 of 14 (50%), and
      progressive disease in 2 of 14 (14%) patients. Eleven patients (79%), including 5
      with partial response and 6 with stable disease, demonstrated a positive gain in
      ROM (range of 3% to 94% improvement in deficit). Of 13 patients with measurable
      changes at 6 months, the average improvement in ROM deficit was 24.2%
      (interquartile range, 15.5% to 30.5%; P = .011). This trial is registered at
      http://clinicaltrials.gov as NCT007020689. 

PMID- 25771404
TI  - Predicting intrapartum fetal compromise using the fetal cerebro-umbilical ratio.
AB  - INTRODUCTION: The aim of this study was to explore the association between the
      cerebro-umbilical ratio measured at 35-37 weeks and intrapartum fetal compromise.
      METHODS: This retrospective cross sectional study was conducted at the Mater
      Mothers' Hospital in Brisbane, Australia. Maternal demographics and fetal Doppler
      indices at 35-37 weeks gestation for 1381 women were correlated with intrapartum
      and neonatal outcomes. RESULTS: Babies born by caesarean section or instrumental
      delivery for fetal compromise had the lowest median cerebro-umbilical ratio 1.60
      (IQR 1.22-2.08) compared to all other delivery groups (vaginal delivery,
      emergency delivery for failure to progress, emergency caesarean section for other
      reasons or elective caesarean section). The percentage of infants with a cerebro
      umbilical ratio <10th centile that required emergency delivery (caesarean section
      or instrumental delivery) for fetal compromise was 22%, whereas only 7.3% of
      infants with a cerebro-umbilical ratio between the 10th-90th centile and 9.6% of
      infants with a cerebro-umbilical ratio > 90th centile required delivery for the
      same indication (p < 0.001). A lower cerebro-umbilical ratio was associated with
      an increased risk of emergency delivery for fetal compromise, OR 2.03 (95% CI
      1.41-2.92), p < 0.0001. DISCUSSION: This study suggests that a low fetal cerebro
      umbilical ratio measured at 35-37 weeks is associated with a greater risk of
      intrapartum compromise. This is a relatively simple technique which could be used
      to risk stratify women in diverse healthcare settings.

PMID- 25771405
TI  - STAT3 cooperates with the non-canonical NF-kappaB signaling to regulate pro-labor
      genes in the human placenta.
AB  - INTRODUCTION: Our recent studies have shown that constitutively activated non
      canonical RelB/NF-kappaB2 (p52) in the human placenta positively regulates the
      pro-labor genes CRH and COX-2. STAT3 regulates NF-kappaB2 (p100) processing to
      active p52, and in turn, nuclear activation of RelB/p52, by directly binding to
      p100/p52 in a variety of cancer cells. In the current study, we tested the
      hypothesis that STAT3 is involved in regulation of pro-labor genes by associating
      with RelB/p52 heterodimers in the human placenta. METHODS: We used a variety of
      techniques including immunohistochemical staining, gene silencing, ectopic
      expression, chromatin immunoprecipitation, Western blot, RT-qPCR, and
      immunofluorescence assays in primary culture of cytotrophoblast and placental
      tissues. RESULTS: We found that knockdown of STAT3 led to down-regulation of both
      CRH and COX-2 in a dose-dependent manner. By using chromatin immunoprecipitation,
      we further showed that interaction of RelB with the CRH or COX-2 gene promoters
      decreased when STAT3 was depleted. Immunofluorescence demonstrated co
      localization of STAT3 with RelB or p100/p52 in both the cytoplasm and nucleus of
      term cytotrophoblasts. DISCUSSION: Collectively, these results suggest that STAT3
      constitutes part of the RelB/p52-containing activator complex that positively
      regulates pro-labor genes in the human placenta.

PMID- 25771407
TI  - Modeling strategies for plant survival, growth and reproduction.

PMID- 25771406
TI  - Chinese herbal medicine for miscarriage affects decidual micro-environment and
      fetal growth.
AB  - INTRODUCTION: Intrauterine growth restriction complicates 5-10% of pregnancies.
      This study aims to test the hypothesis that Chinese herbal formula, JLFC01,
      affects pregnancy and fetal development by modulating the pro-inflammatory
      decidual micro-environment. METHODS: Human decidua from gestational age-matched
      elective terminations or incomplete/missed abortion was immunostained using anti
      CD68 + anti-CD86 or anti-CD163 antibodies. qRT-PCR and Luminex assay measured the
      effects of JLFC01 on IL-1beta- or TNF-alpha-induced cytokine expression in first
      trimester decidual cells and on an established spontaneous abortion/intrauterine
      growth restriction (SA/IUGR)-prone mouse placentae. The effect of JLFC01 on human
      endometrial endothelial cell angiogenesis was evaluated by average area, length
      and numbers of branching points of tube formation. Food intake, litter size,
      fetal weight, placental weight and resorption rate were recorded in SA/IUGR-prone
      mouse treated with JLFC01. qRT-PCR, Western blot and immunohistochemistry
      assessed the expression of mouse placental IGF-I and IGF-IR. RESULTS: In
      spontaneous abortion, numbers of decidual macrophages expressing CD86 and CD163
      are increased and decreased, respectively. JLFC01 reduces IL-1beta- or TNF-alpha
      induced GM-CSF, M-CSF, C-C motif ligand 2 (CCL2), interferon-gamma-inducible
      protein-10 (IP-10), CCL5 and IL-8 production in first trimester decidual cells.
      JLFC01 suppresses the activity of IL-1beta- or TNF-alpha-treated first trimester
      decidual cells in enhancing macrophage-inhibited angiogenesis. In SA/IUGR-prone
      mice, JLFC01 increases maternal food intake, litter size, fetal and placental
      weight, and reduces fetal resorption rate. JLFC01 induces IGF-I and IGF-IR
      expression and inhibits M-CSF, CCL2, CCL5, CCL11, CCL3 and G-CSF expression in
      the placentae. DISCUSSION: JLFC01 improves gestation by inhibiting decidual
      inflammation, enhancing angiogenesis and promoting fetal growth.

PMID- 25771408
TI  - Phylogenetic and phylogeographic mapping of the avian coronavirus spike protein
      encoding gene in wild and synanthropic birds.
AB  - The evolution and population dynamics of avian coronaviruses (AvCoVs) remain
      underexplored. In the present study, in-depth phylogenetic and Bayesian
      phylogeographic studies were conducted to investigate the evolutionary dynamics
      of AvCoVs detected in wild and synanthropic birds. A total of 500 samples,
      including tracheal and cloacal swabs collected from 312 wild birds belonging to
      42 species, were analysed using molecular assays. A total of 65 samples (13%)
      from 22 bird species were positive for AvCoV. Molecular evolution analyses
      revealed that the sequences from samples collected in Brazil did not cluster with
      any of the AvCoV S1 gene sequences deposited in the GenBank database. Bayesian
      framework analysis estimated an AvCoV strain from Sweden (1999) as the most
      recent common ancestor of the AvCoVs detected in this study. Furthermore, the
      analysis inferred an increase in the AvCoV dynamic demographic population in
      different wild and synanthropic bird species, suggesting that birds may be
      potential new hosts responsible for spreading this virus. 

PMID- 25771409
TI  - Curing non-small cell lung cancer with radiotherapy: no longer an oxymoron.

PMID- 25771410
TI  - Molecular determinants of radiation response in non-small cell lung cancer.
AB  - Non-small cell lung cancers are now recognized to contain considerable
      heterogeneity and molecular diversity. Substantial progress has been made
      regarding molecular determinants of response to targeted agents in advanced lung
      cancer, and recent findings have revealed subsets of patients with driver
      mutations that respond rapidly to selective inhibitors. In addition, new
      approaches to disrupting DNA repair and inflammation and activation of the immune
      system are being explored. A key question in the field is whether therapeutic
      multimodality options incorporating radiation therapy can capitalize on the gains
      made in systemic therapy. 

PMID- 25771411
TI  - To SABR or not to SABR? Indications and contraindications for stereotactic
      ablative radiotherapy in the treatment of early-stage, oligometastatic, or
      oligoprogressive non-small cell lung cancer.
AB  - Stereotactic ablative radiotherapy (SABR) is a highly effective treatment for
      early-stage non-small cell lung cancer. Although direct comparisons from
      randomized trials are not available, rates of both primary tumor control and
      distant metastasis are similar between SABR and surgery. Overall survival is
      lower after SABR compared with surgery, largely reflecting that a primary
      selection criterion for SABR has been medical inoperability because of decreased
      cardiopulmonary function and other comorbidities that lead to decreased survival
      independent of non-small cell lung cancer. Survival outcomes between SABR and
      surgery are much more similar in propensity-matched cohorts. Newer potential
      indications for SABR include treatment of operable patients; of oligometastatic
      lung cancer, in which SABR has emerged as an alternative to metastasectomy; and
      of oligoprogressive lung cancer, an attractive concept especially as improved
      personalized systemic therapies emerge, and prospective trials are currently
      being conducted in these settings. Although toxicity in modern series is low,
      SABR is clearly capable of producing fatal complications, and understanding the
      risk factors and approaches for mitigating them has been emerging in recent
      years. Thus, appropriate patient selection is a vital, evolving, and
      controversial topic. 

PMID- 25771412
TI  - Hypoxia as a cause of treatment failure in non-small cell carcinoma of the lung.
AB  - Hypoxia is an important factor in tumor biology and is both a predictive and a
      prognostic factor in non-small cell lung cancer. The negative effect of low
      oxygenation on radiation therapy effect has been known for decades, but more
      recent research has emphasized that hypoxia also has a profound effect on a
      tumor's aggression and metastatic propensity. In this review, current knowledge
      on both these aspects of treatment failure in NSCLC due to hypoxia has been
      discussed, along with a presentation of modern methods for hypoxia measurement
      and current therapeutical interventions to circumvent the negative effect of
      hypoxia on treatment results. 

PMID- 25771413
TI  - Accelerated repopulation as a cause of radiation treatment failure in non-small
      cell lung cancer: review of current data and future clinical strategies.
AB  - Despite convincing evidence that the principles of accelerated repopulation would
      open up additional therapeutic opportunities in the treatment of advanced-stage
      non-small cell lung cancer, this strategy has been generally underexplored. The
      implementation of accelerated radiotherapy schedules has been hampered by
      logistical barriers, concerns about acute toxicity, and the prioritization of
      integrating concurrent chemotherapy into the standard treatment platform. At
      present, it is unclear to what extent accelerated fractionation will influence
      future treatment paradigms in non-small cell lung cancer, although technical
      advances in radiotherapy, allowing higher dose delivery with reduced toxicity,
      could permit the development of more convenient and tolerable forms of
      accelerated schedules. 

PMID- 25771416
TI  - Intensity-modulated radiotherapy, not 3 dimensional conformal, is the preferred
      technique for treating locally advanced disease with high-dose radiotherapy: the
      argument against.
AB  - Intensity-modulated radiotherapy (IMRT) allows the delivery of high-dose
      radiotherapy to target volumes, while sparing adjacent normal tissues. This has
      been mooted as a method of treating larger and otherwise untreatable lung cancers
      or of escalating radiotherapy doses. The possibility of achieving these aims has
      been confirmed in many planning studies, but there is little supporting clinical
      data. No randomized trial has compared conformal and IMRT, few studies have
      reported the late outcomes of IMRT, and there is no evidence for improved control
      of lung cancer with increased radiation dose. Currently IMRT should be regarded
      as a promising but unproven experimental therapy in locally advanced non-small
      cell lung cancer. Searches of PubMed were performed looking for the terms "lung
      cancer and radiotherapy" and "lung cancer and intensity-modulated radiotherapy."
      The former was carried out for the period 2007, when the author last reviewed
      this topic, until 2014 and the latter from the first reference to this topic to
      the present. The first search produced 8000 and the second 929 hits. A standard
      hierarchy of evidence exists for interventions in medicine, ranging from
      systematic reviews of randomized trials to case-control studies and mechanism
      based reasoning. The best evidence so far available for IMRT in stage III lung
      cancer is level 3 or 4 (low level evidence), and no currently accruing phase II
      or phase III trials are listed on the National Cancer Institute clinical trials
      website, although 1 study at the MD Anderson is open but not currently recruiting
      patients. This evidence will be reviewed. It would not be regarded as remotely
      adequate for the licensing of a new pharmacologic agent, and it does not seem
      unreasonable that the same standards of evidence for efficacy and safety should
      apply to the 2 branches of nonsurgical oncology. 

PMID- 25771415
TI  - Intensity-modulated radiotherapy, not 3 dimensional conformal, is the preferred
      technique for treating locally advanced lung cancer.
AB  - When used to treat lung cancer, intensity-modulated radiotherapy (IMRT) can
      deliver higher dose to the targets and spare more critical organs in lung cancer
      than can 3-dimensional conformal radiotherapy. However, tumor-motion management
      and optimized radiotherapy planning based on 4-dimensional computed tomography
      scanning are crucial to maximize the benefit of IMRT and to eliminate or minimize
      potential uncertainties. This article summarizes these strategies and reviews
      published findings supporting the safety and efficacy of IMRT for lung cancer. 

PMID- 25771417
TI  - Superiority of concomitant chemoradiation over sequential chemoradiation in
      inoperable, locally advanced non-small cell lung cancer: challenges in the
      selection of appropriate chemotherapy.
AB  - Treatment of inoperable, locally advanced non-small cell lung cancer (LA-NSCLC)
      is challenging and requires a multidisciplinary approach considering both local
      therapy and systemic therapy. Based on the results from several phase III studies
      and 2 meta-analyses, the use of concomitant chemoradiation therapy (ChRT) could
      significantly improve overall survival and is considered the standard of care in
      LA-NSCLC with good performance status. Currently, no evidence has shown a
      significant survival benefit of third-generation regimens applied in combination
      with ChRT compared with second-generation regimens. For regimens concomitant with
      radiation therapy, full-dose chemotherapy (such as cisplatin and etoposide or
      cisplatin and vinblastine) might be preferred. Additional full-dose consolidation
      paclitaxel-carboplatin is recommended when patients receive weekly paclitaxel
      carboplatin ChRT. Effective novel chemotherapy agents or targeted therapies are
      required to further improve the outcome of patients with LA-NSCLC. In addition,
      personalized medicine concomitant with radiation therapy is a promising approach.
      However, little evidence exists concerning the effectiveness of this novel
      approach. 

PMID- 25771414
TI  - Nondosimetric risk factors for radiation-induced lung toxicity.
AB  - The decision to administer a radical course of radiotherapy (RT) is largely
      influenced by the dose-volume metrics of the treatment plan, but what are the
      patient-related and other factors that may independently increase the risk of
      radiation lung toxicity? Poor pulmonary function has been regarded as a risk
      factor and a relative contraindication for patients undergoing radical RT, but
      recent evidence suggests that patients with poor spirometry results may tolerate
      conventional or high-dose RT as well as, if not better than, patients with normal
      function. However, caution may need to be exercised in patients with underlying
      interstitial pulmonary fibrosis. Furthermore, there is emerging evidence of
      molecular markers of increased risk of toxicity. This review discusses patient
      related risk factors other than dosimetry for radiation lung toxicity. 

PMID- 25771418
TI  - The evolving role of molecular imaging in non-small cell lung cancer
      radiotherapy.
AB  - Molecular imaging with positron emission tomography (PET) has dramatically
      changed the management of patients with lung cancer who are treated with
      radiotherapy. Uptake of the most widely used PET radiopharmaceutical (18)F
      fluorodeoxyglucose identifies lung nodules or intrathoracic lymph nodes as likely
      to be malignant and frequently identifies previously unsuspected sites of
      malignant disease outside the thorax. Patients with non-small cell lung cancer,
      especially those with apparently more advanced locoregional disease to start
      with, are often upstaged, and this has a profound effect on their subsequent
      management. Better patient selection, primarily by excluding patients with PET
      detected advanced disease, and better targeting of radiotherapy to avoid
      geographic miss have contributed significantly to improvements in outcome in
      recent series of patients treated with definitive chemoradiation. Advances in
      motion management with 4-dimensional PET/computed tomography and research into
      sequential imaging during treatment to permit response-adapted therapy hold
      promise for further improvements in treatment outcomes. Research involving novel
      PET tracers that can characterize biological properties of tumors, such as
      proliferation or hypoxia, may help develop more personalized approaches to
      patient management in the future. 

PMID- 25771419
TI  - International patterns of radiotherapy practice for non-small cell lung cancer.
AB  - Radiotherapy is an important treatment modality for non-small cell lung cancer
      (NSCLC). There are models of radiotherapy utilization that estimate the
      proportion of patients with NSCLC who have an evidence-based indication for
      radiotherapy. These estimates range from 46%-68% for radiotherapy utilization at
      diagnosis and 64%-75% overall. However, actual radiotherapy utilization
      throughout much of the world is lower than this, ranging from 28%-53%, with the
      largest differences between actual and estimated radiotherapy utilization seen in
      stage III NSCLC. Some of this discrepancy is attributable to the assumptions in
      the models that are based on broad factors such as stage and performance status.
      Characteristics of the population with underlying lung cancer that often has
      comorbidities or compromised respiratory function also influence the ability to
      deliver radiotherapy safely. Sociodemographic factors such as race and income
      have been found to affect access to radiotherapy in certain jurisdictions. The
      type of clinician or medical setting the patient presents to initially can also
      influence radiotherapy use in NSCLC. Potential solutions to improve appropriate
      radiotherapy utilization for NSCLC include restructuring models of care to ensure
      that all patients with lung cancer are managed within a multidisciplinary team
      including a radiation oncologist. 

PMID- 25771420
TI  - Contributions of Caucasian-associated bone mass loci to the variation in bone
      mineral density in Vietnamese population.
AB  - BACKGROUND AND AIM: Bone mineral density (BMD) is under strong genetic
      regulation, but it is not clear which genes are involved in the regulation,
      particularly in Asian populations. This study sought to determine the association
      between 29 genes discovered by Caucasian-based genome-wide association studies
      and BMD in a Vietnamese population. METHODS: The study involved 564 Vietnamese
      men and women aged 18 years and over (average age: 47 years) who were randomly
      sampled from the Ho Chi Minh City. BMD at the femoral neck, lumbar spine, total
      hip and whole body was measured by DXA (Hologic QDR4500, Bedford, MA, USA).
      Thirty-two single nucleotide polymorphisms (SNPs) in 29 genes were genotyped
      using Sequenom MassARRAY technology. The magnitude of association between SNPs
      and BMD was analyzed by the linear regression model. The Bayesian model average
      method was used to identify SNPs that are independently associated with BMD.
      RESULTS: The distribution of genotypes of all, but two, SNPs was consistent with
      the Hardy-Weinberg equilibrium law. After adjusting for age, gender and weight, 3
      SNPs were associated with BMD: rs2016266 (SP7 gene), rs7543680 (ZBTB40 gene), and
      rs1373004 (MBL2/DKK1 gene). Among the three genetic variants, the SNP rs2016266
      had the strongest association, with each minor allele being associated with ~0.02
      g/cm(2) increase in BMD at the femoral neck and whole body. Each of these genetic
      variant explained about 0.2 to 1.1% variance of BMD. All other SNPs were not
      significantly associated with BMD. CONCLUSION: These results suggest that genetic
      variants in the SP7, ZBTB40 and MBL2/DKK1 genes are associated with BMD in the
      Vietnamese population, and that the effect of these genes on BMD is likely to be
      modest.

PMID- 25771421
TI  - Analyses of bone modeling and remodeling using in vitro reconstitution system
      with two-photon microscopy.
AB  - Bone modeling and remodeling are cellular events during which osteoblast lineage
      cells and osteoclasts interact. During these events, cells undergo drastic
      changes with time as they become differentiated. Their morphology, topology, and
      activity are affected by other cells and the extracellular matrices. Since the
      mechanisms underlying the cellular events of bone metabolism have not been
      elucidated, there is a need for systems to analyze these cellular networks and
      their microenvironments spatiotemporally at the cellular level. Here we report a
      novel in vitro system for reconstituting the bone cell network of osteoclasts,
      osteoblasts, and osteocytes in the mineralized nodule, allowing for observation
      of bone modeling and remodeling phenomena by 2-photon microscopy. Using this
      system, the change in morphology of osteoblasts from cuboidal to flat cells was
      observed and measured during the formation of mineralized nodules. Furthermore,
      the recruitment of osteoblasts to resorption pits and their replenishment by
      newly formed matrices were successfully observed, providing strong evidence for
      the coupling of bone resorption and bone formation at cellular level. During such
      remodeling cycle, flat osteoblasts that survived more than 7 weeks were recruited
      to resorption pits, where they became cuboidal osteoblasts that express
      osteocalcin. This novel system permitted the elucidation of cellular behavior
      during bone modeling and remodeling, and can be used to analyze cellular events
      involved in bone metabolism.

PMID- 25771423
TI  - Validation of the Core Outcome Measures Index in Patients With Femoroacetabular
      Impingement.
AB  - PURPOSE: To evaluate a short, hip-oriented outcome instrument, based on the Core
      Outcome Measures Index (COMI), in patients undergoing surgery for
      femoroacetabular impingement (FAI). METHODS: The following full-length
      questionnaires were completed preoperatively and at 6 and 12 months
      postoperatively by 159 consecutive FAI patients: Hip Outcome Score (HOS); Oxford
      Hip Score; Western Ontario and McMaster Universities Arthritis Index; Short Form
      12 Health Survey; World Health Organization Quality of Life questionnaire, short
      version; and EuroQol-Five Dimensional index. The scores for the 6 hip-oriented
      Core Outcome Measures Index (COMI-Hip) items-addressing pain, function, symptom
      specific well-being, quality of life, and disability-were extracted from
      established full-length questionnaires, and their performance as an index was
      compared with that of the full-length instruments. RESULTS: Scores for the single
      items of the COMI-Hip questionnaire correlated well with the scores for the
      corresponding full-length instruments from which they were extracted (r = -0.89
      to -0.62, P < .001). The COMI-Hip sum score also correlated well with the Oxford
      Hip Score and the Western Ontario and McMaster Universities Arthritis Index pain
      and function scores (r = -0.85 to -0.70, P < .001), as well as with the HOS (r = 
      0.72 to -0.60, P < .001), an instrument specifically developed for assessing FAI
      patients. Internal responsiveness (Cohen d for effect size) of the COMI-Hip sum
      score from preoperatively to 12 months postoperatively was similar to that of the
      HOS activities-of-daily living subscale (d = -0.76 and d = -0.68, respectively; P
      < .001). Significant correlations were found between the change scores of the
      COMI-Hip sum score and those of the HOS activities-of-daily living and sport
      subscales at 6 months (r = -0.62 and r = -0.60, respectively; P < .001) and 12
      months (r = -0.69 and r = -0.61, respectively; P < .001), showing the external
      responsiveness of the COMI-Hip. CONCLUSIONS: The COMI-Hip is a simple yet valid
      and responsive outcome instrument for the efficient assessment of patients
      undergoing surgery for FAI. It performs at least as well as the current reference
      instrument for FAI, the HOS, and can therefore be considered a potentially
      valuable instrument for routine use in both research and clinical practice. LEVEL
      OF EVIDENCE: Level II, development of diagnostic criteria based on consecutive
      patients (with universally applied reference gold standard).

PMID- 25771422
TI  - FRAX (Aus) and falls risk: Association in men and women.
AB  - PURPOSE: The WHO fracture risk prediction tool (FRAX(r)) utilises clinical risk
      factors to estimate the probability of fracture over a 10-year period. Although
      falls increase fracture risk, they have not been incorporated into FRAX. It is
      currently unclear if FRAX captures falls risk and whether addition of falls would
      improve fracture prediction. We aimed to investigate the association of falls
      risk and Australian-specific FRAX. METHODS: Clinical risk factors were documented
      for 735 men and 602 women (age 40-90 yr) assessed at follow-up (2006-2010 and
      2000-2003, respectively) of the Geelong Osteoporosis Study. FRAX scores with and
      without BMD were calculated. A falls risk score was determined at the time of BMD
      assessment and self-reported incident falls were documented from questionnaires
      returned one year later. Multivariable analyses were performed to determine: (i)
      cross-sectional association between FRAX scores and falls risk score (Elderly
      Falls Screening Test, EFST) and (ii) prospective relationship between FRAX and
      time to a fall. RESULTS: There was an association between FRAX (hip with BMD) and
      EFST scores (beta = 0.07, p < 0.001). After adjustment for sex and age, the
      relationship became non-significant (beta = 0.00, p = 0.79). The risk of incident
      falls increased with increasing FRAX (hip with BMD) score (unadjusted HR 1.04,
      95% CI 1.02, 1.07). After adjustment for age and sex, the relationship became non
      significant (1.01, 95% CI 0.97, 1.05). CONCLUSIONS: There is a weak positive
      correlation between FRAX and falls risk score, that is likely explained by the
      inclusion of age and sex in the FRAX model. These data suggest that FRAX score
      may not be a robust surrogate for falls risk and that inclusion of falls in
      fracture risk assessment should be further explored.

PMID- 25771424
TI  - Serial changes in knee muscle strength after anterior cruciate ligament
      reconstruction using hamstring tendon autografts.
AB  - PURPOSE: The purpose of this study was to evaluate serial changes in quadriceps
      and hamstring muscle strength over the first postoperative year in patients who
      underwent anterior cruciate ligament (ACL) reconstruction with an autologous
      hamstring tendon graft and to reveal which of these 2 muscles lost more strength
      and recovered more slowly after autologous hamstring ACL reconstruction. METHODS:
      Isokinetic muscle strength was measured preoperatively and at 6 months and 1 year
      postoperatively in 20 patients who underwent ACL reconstruction. The maximal
      torque (60 degrees /s) and total work (180 degrees /s) of the quadriceps and
      hamstring were evaluated using an isokinetic testing device. The isokinetic
      muscle strength and endurance of the injured legs were expressed as percentages
      of those of the uninjured legs at the same time point. RESULTS: Both quadriceps
      and hamstring muscle strength at 60 degrees /s and endurance at 180 degrees /s of
      the injured relative to the uninjured leg was 50% preoperatively. Quadriceps
      muscle strength and endurance of the injured leg increased to 70% at 6 months and
      80% at 1 year postoperatively, whereas hamstring muscle strength and endurance
      increased to 80% at 6 months and 80% at 1 year. CONCLUSIONS: Knee muscle strength
      recovered progressively after ACL reconstruction using autologous hamstring
      tendons but did not fully recover, being about 80% that of the uninjured leg even
      1 year after surgery. LEVEL OF EVIDENCE: Level IV, therapeutic case series.

PMID- 25771425
TI  - Trends in Ankle Arthroscopy and Its Use in the Management of Pathologic
      Conditions of the Lateral Ankle in the United States: A National Database Study.
AB  - PURPOSE: This study aimed to investigate current trends in ankle arthroscopy
      across time, sex, age, and region of the United States as well as the use of
      ankle arthroscopy in the management of lateral ankle instability. METHODS:
      Patients who underwent ankle arthroscopy and those who underwent ankle
      arthroscopy and lateral ankle ligament repair or peroneal retinacular repair from
      2007 through 2011 were identified using the PearlDiver national database. These
      searches yielded volumes of unique patients, sex and age distribution, and
      regional volumes of patients. Chi-square linear-by-linear association analysis
      was used for comparisons, with P < .05 considered significant. RESULTS: We
      identified 15,366 ankle arthroscopy procedures in the database from 2007 to 2011.
      Over the 5-year study period, there was a significant increase in the overall
      number of ankle arthroscopies being performed, from 2,814 in 2007 to 3,314 in
      2011 (P < .0001). Female patients had ankle arthroscopy more frequently than did
      male patients (P = .027). The majority of patients who had ankle arthroscopy were
      between the ages of 30 and 49 years. The use of ankle arthroscopy during lateral
      ligament repair procedures increased from 37.2% in 2007 to 43.7% in 2011 (P <
      .0001). The incidence of combined ankle arthroscopy and peroneal tendon
      retinacular repair increased 50%, from 2.8/100 ankle arthroscopies in 2007 to
      4.2/100 ankle arthroscopies in 2011 (P < .0001). CONCLUSIONS: The incidence of
      ankle arthroscopy increased significantly from 2007 to 2011, outpacing shoulder,
      knee, and elbow arthroscopy. Ankle arthroscopy was performed more frequently in
      female patients and most commonly in patients younger than 50 years. The use of
      ankle arthroscopy in the surgical management of lateral ankle instability also
      increased significantly. The incidence of concomitant ankle arthroscopy and
      lateral ligament repair increased significantly, as did the incidence of
      concomitant ankle arthroscopy and repair of peroneal tendon subluxation. LEVEL OF
      EVIDENCE: Level IV, therapeutic case series.

PMID- 25771426
TI  - Volumetric Damage to the Femoral Physis During Double-Bundle Posterior Cruciate
      Ligament Reconstruction: A Magnetic Resonance Imaging Computer Modeling Study.
AB  - PURPOSE: The purpose of this study was to use computer models to evaluate the
      volume of femoral physeal disruption in double-bundle posterior cruciate ligament
      (PCL) reconstruction in patients with open physes. METHODS: Ten skeletally
      immature patients (6 girls and 4 boys) were selected for this study. The magnetic
      resonance imaging scans of each patient were converted into a 3-dimensional model
      using computer-aided design/computer-aided manufacturing software. The software
      allowed the users to differentiate the epiphyseal, physeal, and metaphyseal
      tissues. This allowed for quantification of volume removed of each tissue type.
      Furthermore, we used the 3-dimensional models to simulate an anatomic double
      bundle technique using 6-, 7-, 8-, and 9-mm-diameter tunnels. The software method
      reflects an inside-out drilling technique. RESULTS: For drill holes of all
      diameters, the posteromedial tunnels exited the knee inferior to the physis, thus
      avoiding physeal damage. In contrast, all the anterolateral tunnels perforated
      the physis. The results for the percent of total physis removed are as follows: 6
      mm tunnel, 1.79% +/- 0.99%; 7-mm tunnel, 2.23% +/- 1.19%; 8-mm tunnel, 3.00% +/-
      1.54%; and 9-mm tunnel, 3.84% +/- 1.73%. CONCLUSIONS: This computer modeling
      simulation of double-bundle PCL reconstruction in skeletally immature knees found
      that the posteromedial tunnel avoided disruption of the distal femoral physis. In
      contrast, the anterolateral tunnel did disrupt the physis with all drill hole
      sizes (6 to 9 mm), but all had a less than 4% volume of total physis removed.
      CLINICAL RELEVANCE: A clear understanding of the drill hole position may reduce
      the volume of physeal injury during double-bundle PCL reconstruction. This study
      shows that physeal disruption of less than the experimental 7% threshold that has
      been shown to cause physeal arrest may not cause arrest, but this is still
      speculative.

PMID- 25771427
TI  - Cumulative Radiation Exposure to Patients Undergoing Arthroscopic Hip
      Preservation Surgery and Occupational Radiation Exposure to the Surgical Team.
AB  - PURPOSE: To quantify cumulative radiation exposure in patients undergoing
      arthroscopic hip preservation surgery and occupational exposure to operating room
      (OR) personnel during such surgery; a secondary objective of this study was to
      identify factors affecting radiation exposure in patients undergoing hip
      arthroscopy. METHODS: Radiation exposure from all preoperative and intraoperative
      imaging studies was determined for 52 patients undergoing hip arthroscopy.
      Cumulative and effective radiation doses were calculated and correlated with
      pathology and body mass index (BMI). Badge dosimeters were worn by OR personnel
      to measure cumulative occupational exposure. A highly sensitive portable ion
      chamber was used to evaluate the radiation scatter during surgery performed on a
      high-BMI patient and a low-BMI patient to reflect a "worst-case scenario" and
      "best-case scenario," respectively. RESULTS: Forty-three patients underwent
      procedures for femoroacetabular impingement (FAI) and 9 underwent procedures for
      soft-tissue pathologies (ST). The median cumulative exposure was 8.6 mGy and 5.0
      mGy for FAI patients and ST patients, respectively (P = .01). The cumulative
      effective radiation dose was 490 mrem and 350 mrem for FAI patients and ST
      patients, respectively (P = .47). BMI significantly correlated with cumulative
      exposure (P = .0004) and trended toward significance with cumulative effective
      dose (P = .073). OR staff cumulative occupational exposure was low (9 mrem for
      the surgeon). Ion chamber data showed that increasing patient BMI resulted in
      increased occupational exposure. CONCLUSIONS: The median cumulative effective
      radiation dose to patients undergoing arthroscopic hip preservation surgery is
      490 mrem and results in an excess lifetime risk of death from cancer of 0.025%.
      Greater BMI correlates with increased cumulative radiation exposure and may
      increase risk to OR personnel. Occupational exposure to the surgical team from
      hip arthroscopy ranges from 7 to 9 mrem per 50 hip arthroscopies (+0.0005% excess
      lifetime risk of death from cancer). LEVEL OF EVIDENCE: Level IV, diagnostic.

PMID- 25771428
TI  - Biosynthesis of silver nanoparticles using Momordica charantia leaf broth:
      Evaluation of their innate antimicrobial and catalytic activities.
AB  - Silver nanoparticles (AgNPs) were prepared through green route with the aid of
      Momordica charantia leaf extract as both reductant and stabilizer. X-ray
      diffraction pattern (XRD) and selected area electron diffraction (SAED) fringes
      revealed the structure of AgNPs as face centered cubic (fcc). Morphological
      studies elucidate the nearly spherical AgNPs formation with particle size in
      nanoscale. Biosynthesized AgNPs were found to be photoluminescent and UV-Vis
      absorption spectra showed one surface plasmon resonance peak (SPR) at 424nm
      attesting the spherical nanoparticles formation. XPS study provides the surface
      chemical nature and oxidation state of the synthesized nanoparticles. FTIR
      spectra ascertain the reduction and capping nature of phytoconstituents of leaf
      extract in AgNPs synthesis. Further, these AgNPs showed effective antimicrobial
      activity against tested pathogens and thus applicable as potent antimicrobial
      agent. In addition, the synthesized AgNPs were observed to have an excellent
      catalytic activity on the reduction of methylene blue by M. charantia which was
      confirmed by the decrement in maximum absorbance values of methylene blue with
      respect to time and is ascribed to electron relay effect.

PMID- 25771429
TI  - Monitoring brain damage using bioimpedance technique in a 3D numerical model of
      the head.
AB  - Disturbance in the blood supply to the brain causes a stroke or cerebrovascular
      accident. This can be due to ischemia caused by blockage (thrombosis, arterial
      embolism) or a hemorrhage. In this study, the feasibility of basic electrical
      impedance technique for monitoring such damage was analyzed using a computerized
      model. Simulations were conducted on a realistic 3D numerical model of the head.
      Tissues were assumed to act as linear isotropic volume conductors, and the quasi
      static approximation was applied. Electrical potentials were calculated by
      solving Poisson's equation, using the finite volume method and the successive
      over relaxation method. Left-right asymmetry was calculated for several
      conductivities and volumes of the damaged region. The results were compared with
      the left-right asymmetry in a head model with normal brain. A negative asymmetry
      was revealed for blockage (i.e. the potential amplitude over the ischemic
      hemisphere was greater than that over the intact hemisphere). In case of
      hemorrhage, a positive asymmetry was found. Furthermore, correlation was found
      between the location of the damaged region and the electrodes with significant
      asymmetry. The 3D numerical simulations revealed that the electrical conductivity
      and the size of the damaged tissue have an effect on the left-right asymmetry of
      the surface potential. 

PMID- 25771430
TI  - Mechanical characterization of bone anchors used with a bone-attached, parallel
      robot for skull surgery.
AB  - Bone-attached robots and microstereotactic frames, intended for deep brain
      stimulation and minimally invasive cochlear implantation, typically attach to a
      patient's skull via bone anchors. A rigid and reliable link between such devices
      and the skull is mandatory in order to fulfill the high accuracy demands of
      minimally invasive procedures while maintaining patient safety. In this paper, a
      method is presented to experimentally characterize the mechanical properties of
      the anchor-bone linkage. A custom-built universal testing machine is used to
      measure the pullout strength as well as the spring constants of bone anchors
      seated in four different bone substitutes as well as in human cranial bone.
      Furthermore, the angles at which forces act on the bone anchors are varied to
      simulate realistic conditions. Based on the experimental results, a substitute
      material that has mechanical properties similar to those of cranial bone is
      identified. The results further reveal that the pullout strength of the
      investigated anchor design is sufficient with respect to the proposed
      application. However, both the measured load capacity as well as the spring
      constants vary depending on the load angles. Based on these findings, an
      alternative bone anchor design is presented and experimentally validated.
      Furthermore, the results serve as a basis for stiffness simulation and
      optimization of bone-attached microstereotactic frames. 

PMID- 25771431
TI  - Autophagy in polyglutamine disease: Imposing order on disorder or contributing to
      the chaos?
AB  - Autophagy is an essential, fundamentally important catabolic pathway in which
      double membrane-bound vesicles form in the cytosol and encircle macromolecules
      and organelles to permit their degradation after fusion with lysosomes. More than
      a decade of research has revealed that autophagy is required for normal central
      nervous system (CNS) function and plays a central role in maintaining protein and
      organelle quality controls in neurons. Neurodegenerative diseases occur when
      misfolded proteins accumulate and disrupt normal cellular processes, and
      autophagy has emerged as a key arbiter of the cell's homeostatic response to this
      threat. One class of inherited neurodegenerative disease is known as the
      CAG/polyglutamine repeat disorders, and these diseases all result from the
      expansion of a CAG repeat tract in the coding regions of distinct genes.
      Polyglutamine (polyQ) repeat diseases result in the production polyQ-expanded
      proteins that misfold to form inclusions or aggregates that challenge the main
      cellular proteostasis system of the cell, the ubiquitin proteasome system (UPS).
      The UPS cannot efficiently degrade polyQ-expanded disease proteins, and
      components of the UPS are enriched in polyQ disease aggregate bodies found in
      degenerating neurons. In addition to components of the UPS, polyQ protein
      cytosolic aggregates co-localize with key autophagy proteins, even in autophagy
      deficient cells, suggesting that they probably do not reflect the formation of
      autophagosomes but rather the sequestration of key autophagy components.
      Furthermore, recent evidence now implicates polyQ proteins in the regulation of
      the autophagy pathway itself. Thus, a complex model emerges where polyQ proteins
      play a dual role as both autophagy substrates and autophagy offenders. In this
      review, we consider the role of autophagy in polyQ disorders and the therapeutic
      potential for autophagy modulation in these diseases. This article is part of a
      Special Issue entitled "Neuronal Protein". 

PMID- 25771432
TI  - Full length talin stimulates integrin activation and axon regeneration.
AB  - Integrin function is regulated by activation involving conformational changes
      that modulate ligand-binding affinity and downstream signaling. Activation is
      regulated through inside-out signaling which is controlled by many signaling
      pathways via a final common pathway through kindlin and talin, which bind to the
      intracellular tail of beta integrins. Previous studies have shown that the axon
      growth inhibitory molecules NogoA and chondroitin sulfate proteoglycans (CSPGs)
      inactivate integrins. Overexpressing kindlin-1 in dorsal root ganglion (DRG)
      neurons activates integrins, enabling their axons to overcome inhibitory
      molecules in the environment, and promoting regeneration in vivo following dorsal
      root crush. Other studies have indicated that expression of the talin head alone
      or with kindlin can enhance integrin activation. Here, using adult rat DRG
      neurons, we investigate the effects of overexpressing various forms of talin on
      axon growth and integrin signaling. We found that overexpression of the talin
      head activated axonal integrins but inhibited downstream signaling via FAK, and
      did not promote axon growth. Similarly, co-expression of the talin head and
      kindlin-1 prevented the growth-promoting effect of kindlin-1, suggesting that the
      talin head acts as a form of dominant negative for integrin function. Using full
      length talin constructs in PC12 cells we observed that neurite growth was
      enhanced by the expression of wild-type talin and more so by two 'activated'
      forms of talin produced by point mutation (on laminin and aggrecan-laminin
      substrates). Nevertheless, co-expression of full-length talin with kindlin did
      not promote neurite growth more than either molecule alone. In vivo, we find that
      talin is present in PNS axons (sciatic nerve), and also in CNS axons of the
      corticospinal tract. 

PMID- 25771433
TI  - Alopecia as surrogate marker for chemotherapy response in patients with primary
      epithelial ovarian cancer: a metaanalysis of four prospective randomised phase
      III trials with 5114 patients.
AB  - PURPOSE: Alopecia is a common side-effect of chemotherapy and affects quality of
      life of cancer patients. Some patients and physicians believe that alopecia could
      be a surrogate marker for response to chemotherapy and impact on prognosis.
      However, this was never been tested in a sufficiently large cohort of ovarian
      cancer patients. PATIENTS AND METHODS: We analysed retrospectively the meta
      databank of four prospective randomised phase-III-trials with platinum- and
      taxane-based 1st-line-chemotherapy in patients with advanced epithelial ovarian
      cancer (EOC) regarding the impact of alopecia overall outcome. RESULTS: For 4705
      (92.0%) of a total of 5114 EOC-patients alopecia was documented. They had
      received on median six cycle platinum-taxane chemotherapy (range 0-11) with 4186
      (89.0%) having completed ? 6 cycles. Worst alopecia grade was 0 in 2.4%, 1 in
      2.9% and 2 in 94.7% of the patients. In a univariate analysis, including all
      patients, grade-0/1 alopecia was associated with significantly lower progression
      free survival (PFS) and overall survival (OS) compared to grade-2 alopecia.
      However when assessing only those patients who completed ? 6 chemotherapy-cycles
      and hence eliminating the bias of lower total dose of treatment, alopecia failed
      to retain any significant impact on survival in the multivariate analysis. Merely
      the time point of alopecia onset was an independent prognostic factor of
      survival: patients who developed grade-2 alopecia up to cycle 3 had a
      significantly longer OS compared to patients who experienced alopecia later
      during therapy (hazard ratio (HR): 1.25; 95% confidence interval (CI): 1.04
      1.50). CONCLUSIONS: Within a large EOC-patient cohort with 1st-line platinum- and
      taxane-based chemotherapy early onset alopecia appears to be significantly
      associated with a more favourable outcome in those patients who completed ? 6
      chemotherapy cycles. It remains to be elucidated if early onset alopecia is just
      a surrogate marker for higher sensitivity to chemotherapy or if other biological
      effects are underlying.

PMID- 25771434
TI  - Hypobromous acid, a powerful endogenous electrophile: Experimental and
      theoretical studies.
AB  - Hypobromous acid (HOBr) is an inorganic acid produced by the oxidation of the
      bromide anion (Br(-)). The blood plasma level of Br(-) is more than 1,000-fold
      lower than that of chloride anion (Cl(-)). Consequently, the endogenous
      production of HOBr is also lower compared to hypochlorous acid (HOCl).
      Nevertheless, there is much evidence of the deleterious effects of HOBr. From
      these data, we hypothesized that the reactivity of HOBr could be better
      associated with its electrophilic strength. Our hypothesis was confirmed, since
      HOBr was significantly more reactive than HOCl when the oxidability of the
      studied compounds was not relevant. For instance: anisole (HOBr, k2=2.3*10(2)M(
      1)s(-1), HOCl non-reactive); dansylglycine (HOBr, k2=7.3*10(6)M(-1)s(-1), HOCl,
      5.2*10(2)M(-1)s(-1)); salicylic acid (HOBr, k2=4.0*10(4)M(-1)s(-1), non
      reactive); 3-hydroxybenzoic acid (HOBr, k2=5.9*10(4)M(-1)s(-1), HOCl,
      k2=1.1*10(1)M(-1)s(-1)); uridine (HOBr, k2=1.3*10(3)M(-1)s(-1), HOCl non
      reactive). The compounds 4-bromoanisole and 5-bromouridine were identified as the
      products of the reactions between HOBr and anisole or uridine, respectively, i.e.
      typical products of electrophilic substitutions. Together, these results show
      that, rather than an oxidant, HOBr is a powerful electrophilic reactant. This
      chemical property was theoretically confirmed by measuring the positive Mulliken
      and ChelpG charges upon bromine and chlorine. In conclusion, the high
      electrophilicity of HOBr could be behind its well-established deleterious
      effects. We propose that HOBr is the most powerful endogenous electrophile. 

PMID- 25771435
TI  - A new mononuclear manganese(III) complex of an unsymmetrical hexadentate N3O3
      ligand exhibiting superoxide dismutase and catalase-like activity: synthesis,
      characterization, properties and kinetics studies.
AB  - A mononuclear Mn(III) complex MnL.4H2O (H3L=1-[N-(2-pyridylmethyl),N-(2
      hydroxybenzyl)amino]-3-[N'-(2-hydroxybenzyl),N'-(4-methylbenzyl)amino]propan-2
      ol) has been prepared and characterized. This complex catalyzes the dismutation
      of superoxide efficiently, with catalytic rate constant kcat=1.7*10(6)M(-1)s(-1)
      and IC50 1.26MUM, obtained through the nitro blue tetrazolium photoreduction
      inhibition superoxide dismutase assay, in aqueous solution of pH7.8. MnL is also
      able to disproportionate more than 300 equivalents of H2O2 in CH3CN, with initial
      rate of H2O2 decomposition given by ri=kcat [MnL](2) [H2O2] and kcat=1.32(2)mM(
      2)min(-1). The accessibility of the Mn(IV) state (E(p)=0.53V vs. saturated
      calomel electrode), suggests MnL employs a high-valent catalytic cycle to
      decompose O2(-) and H2O2. 

PMID- 25771436
TI  - Global optimal vaccination in the SIR model: properties of the value function and
      application to cost-effectiveness analysis.
AB  - This work focuses on optimal vaccination policies for an Susceptible-Infected
      Recovered (SIR) model; the impact of the disease is minimized with respect to the
      vaccination strategy. The problem is formulated as an optimal control problem and
      we show that the value function is the unique viscosity solution of an Hamilton
      Jacobi-Bellman (HJB) equation. This allows to find the best vaccination policy.
      At odds with existing literature, it is seen that the value function is not
      always smooth (sometimes only Lipschitz) and the optimal vaccination policies are
      not unique. Moreover we rigorously analyze the situation when vaccination can be
      modeled as instantaneous (with respect to the time evolution of the epidemic) and
      identify the global optimum solutions. Numerical applications illustrate the
      theoretical results. In addition the pertussis vaccination in adults is
      considered from two perspectives: first the maximization of DALY averted in
      presence of vaccine side-effects; then the impact of the herd immunity on the
      cost-effectiveness analysis is discussed on a concrete example. 

PMID- 25771437
TI  - Acute changes in soleus H-reflex facilitation and central motor conduction after
      targeted physical exercises.
AB  - We tested the acute effect of exercises targeted simultaneously at cortical and
      brainstem circuits on neural transmission through corticobulbar connections.
      Corticobulbar pathways represent a potential target for rehabilitation after
      spinal cord injury (SCI), which tends to spare brainstem circuits to a greater
      degree than cortical circuits. To explore this concept, able-bodied volunteers
      (n=20) underwent one session each of three exercises targeted at different
      nervous system components: treadmill walking (spinal locomotor circuits),
      isolated balance exercise (brainstem and other pathways), and multimodal balance
      plus skilled hand exercise (hand motor cortex and corticospinal tract). We found
      that short-interval soleus H-reflex facilitation increased after one session of
      balance and multimodal exercise by 13.2+/-4.0% and 8.3+/-4.7%, and slightly
      decreased by 1.9+/-4.4% after treadmill exercise (p=0.042 on ANOVA across
      exercise type). Increases in long-interval H-reflex facilitation were not
      significantly different between exercises. Both balance and multimodal exercise
      increased central motor conduction velocity by 4.3+/-2.6% and 4.5+/-2.8%, whereas
      velocity decreased by 4.3+/-2.7% after treadmill exercise (p=0.045 on ANOVA
      across exercise type). In conclusion, electrophysiological transmission between
      the motor cortex and spinal motor neurons in able-bodied subjects increased more
      following one session of balance exercise than treadmill exercise. 

PMID- 25771438
TI  - A Truncating De Novo Point Mutation in a Young Infant with Severe Menkes Disease.
AB  - Menkes disease is a rare neurodegenerative disorder caused by mutations in ATP7A
      gene. Deficiency in copper-dependent enzymes results in the unique kinky hair
      appearance, neurodegeneration, developmental delay, seizures, failure to thrive
      and other connective tissue or organ abnormalities. Other than biochemical tests,
      DNA-based diagnosis is now playing an important role. More than two hundred
      mutations in ATP7A gene were identified. Early copper supplementation can help
      improve neurological symptoms, but not non-neurological problems. Further
      molecular studies are needed to identify additional mutation types and to
      understand the mechanism of pathogenesis. This may help in discovering the
      possible treatment measures to cure the disease. We present a case with the
      clinical features and biochemical findings, abnormal brain magnetic resonance
      imaging as well as the effects of treatment with copper-histidine. Direct
      sequencing of ATP7A gene revealed a de novo point mutation which resulted in an
      early stop codon with truncated protein.

PMID- 25771439
TI  - Seasonal evaluation of the presence of 46 disinfection by-products throughout a
      drinking water treatment plant.
AB  - In this work, we studied a total of 46 regulated and non-regulated disinfection
      by-products (DBPs) including 10 trihalomethanes (THMs), 13 haloacetic acids
      (HAAs), 6 halonitromethanes (HNMs), 6 haloacetonitriles (HANs) and 11 aldehydes
      at different points in a drinking water treatment plant (DWTP) and its
      distribution network. Determining an increased number of compounds and using
      accurate, sensitive analytical methodologies for new DBPs can be useful to
      overcome some challenges encountered in the comprehensive assessment of the
      quality and safety of drinking water. This paper provides a detailed picture of
      the spatial and seasonal variability of DBP concentrations from raw water to
      distribution network. Samples were collected on a monthly basis at seven
      different points in the four seasons of a year to acquire robust data for DBPs
      and supplementary quality-related water parameters. Only 5 aldehydes and 2 HAAs
      were found in raw water. Chlorine dioxide caused the formation of 3 new aldehydes
      (benzaldehyde included), 5 HAAs and chloroform. The concentrations of DBPs
      present in raw water were up to 6 times higher in the warmer seasons (spring and
      summer). The sedimentation process further increased their concentrations and
      caused the formation of three new ones. Sand filtration substantially removed
      aldehydes and HAAs (15-50%), but increased the levels of THMs, HNMs and HANs by
      up to 70%. Chloramination raised the levels of 8 aldehydes and 7 HAAs; also, it
      caused the formation of monoiodoacetic acid, dibromochloromethane,
      dichloroiodomethane and bromochloroacetonitrile. Therefore, this treatment
      increases the levels of existing DBPs and leads to the formation of new ones to a
      greater extent than does chlorine dioxide. Except for 5 aldehydes, the 23 DBPs
      encountered at the DWTP exit were found at increased concentrations in the warmer
      seasons (HAAs by about 50% and THMs by 350%).

PMID- 25771440
TI  - Direct immobilization of biotin on the micro-patterned PEN foil treated by
      excimer laser.
AB  - Polymers with functionalized surfaces have attracted a lot of attention in the
      last few years. Due to the progress in the techniques of polymer micro
      patterning, miniaturized bioanalytical assays and biocompatible devices can be
      developed. In the presented work, we performed surface modification of
      polyethylene naphthalate (PEN) foil by an excimer laser beam through a
      photolithographic contact mask. The aim was to fabricate micro-patterned areas
      with surface functional groups available for localized covalent immobilization of
      biotin. It was found out that depending on the properties of the laser scans, a
      polymer surface exhibits different degrees of modification and as a consequence,
      different degrees of surface biotinylation can be achieved. Several affinity
      tests with optical detection of fluorescently labeled streptavidin were
      successfully performed on biotinylated micro-patterns of a PEN foil. The polymer
      surface properties were also evaluated by electrokinetic analysis, Fourier
      transform infrared spectroscopy (FTIR), X-ray photoelectron spectroscopy (XPS)
      and atomic force microscopy (AFM). The results have shown that PEN foils can be
      considered suitable substrates for construction of micro-patterned bioanalytical
      affinity assays. 

PMID- 25771442
TI  - Pouch outlet obstruction by psyllium-based bulk laxative bezoar in a patient with
      gastric banding.

PMID- 25771441
TI  - Comparison of results after one year between sleeve gastrectomy and gastric
      bypass in patients with BMI >= 50 kg/m2.
AB  - BACKGROUND: Although laparoscopic sleeve gastrectomy (LSG) was initially
      described as the first step of a 2-stage procedure for high-risk patients
      requiring laparoscopic Roux-en-Y gastric bypass (LRYGB), it is now being used as
      a single-stage procedure. Experience with laparoscopic bariatric surgery is
      growing, such that LRYGB is increasingly feasible for patients with body mass
      index (BMI) >= 50 kg/m2. Nevertheless, outcomes for such category of patients
      following LSG and LRYGB are lacking. OBJECTIVE: To compare weight loss and
      changes in obesity related co-morbidities at one year following LSG with LRYGB in
      patients with BMI >= 50 kg/m2. SETTINGS: The prospective database of a single
      surgery university center was queried for clinical and other relevant data.
      METHODS: From January 2004 to January 2013, 74 and 285 patients underwent LSG or
      LRYGB with a BMI >= 50 kg/m2. At one year, rate of follow-up was 92.8%. Success
      of surgery was defined as % of excess weight loss (%EWL)>= 50% at one year.
      Logistic regression was used to compute odds ratio (OR) to evaluate the success
      at one year of surgery. RESULTS: LSG (N = 74) and LGBP (N = 285) groups did not
      differ for initial BMI (57.2 +/- 7.1 versus 56.7 +/- 5.5 kg/m2; P = .52), % of
      female (64.6% versus 73.7%, P = .13) or major adverse postoperative events (5.7%
      versus 6.7%; P = .85). At one year, the mean percentage of weight loss (%) (22.0
      +/- 7.6 versus 30.3 +/- 7.4; P < .0001) and percentage of excess weight loss (%)
      (40.2 +/- 15.2 versus 55.0 +/- 14.6; P < .0001) and rates of remission of
      diabetes (47.5% versus 70.7%; P = .01) were greater in the LGBP than LSG group.
      In multivariate analyses (OR), LSG was an independent factor of failure of weight
      loss (.12; P < .0001) CONCLUSION: After 1 year of follow-up in patients with a
      BMI >= 50 kg/m2, LRYGB provides better weight loss and resolution in diabetes
      than LSG with similar postoperative morbidity. Further long-term studies are
      needed to confirm these results.

PMID- 25771443
TI  - Body mass index, pain score and Alvarado score are useful predictors of appendix
      visualization at ultrasound in adults.
AB  - The study objective was to find factors predictive of ultrasound visualization of
      the appendix in patients with suspected appendicitis. A total of 238 consecutive
      adult patients (178 women, mean age 38.9 y, weight 58.2 kg, body mass index 22.7)
      who underwent appendiceal ultrasound from January to December 2011 were included.
      Appendicitis was confirmed in 171 patients (171/238, 71.9%). Ultrasound
      sensitivity, specificity and accuracy were 64%, 90% and 71%, respectively. The
      appendix was visualized at ultrasound in 126 patients (group 1) and not
      visualized in 112 patients (group 2). Group 1 had a lower body mass index, higher
      pain score and higher Alvarado score. The chances of visualizing the appendix in
      patients with body mass indexes <=22, pain scores >=6, and Alvarado scores >=6
      were 2.3, 2.9, and 3.8 times higher than those of their counterparts,
      respectively. Therefore, in patients with these factors, the use of ultrasound
      may be beneficial in the diagnosis of acute appendicitis. 

PMID- 25771444
TI  - Theoretical evaluation of the acoustic field in an ultrasonic bioreactor.
AB  - Ultrasound-assisted bioreactors that provide mechanical conditioning to cells
      have broad applicability in tissue engineering, but biological experiments with
      ultrasound are very sensitive to environmental conditions. A mathematical model
      was developed to complement experimental measurements, as well as to describe
      ultrasonic fields existing in regions where measurements are impossible,
      specifically, within microporous tissue engineering scaffolds. The model uniquely
      combines Biot theory to predict the ultrasonic field in the scaffold with an
      electromechanical transducer model to couple the mechanical stimulation
      experienced by cells to the external electrical input. In the specific example
      examined here, cells immobilized on scaffolds are subjected to different forms of
      ultrasonic stimulation due to the formation of standing wave fields and vertical
      high-pressure bands. The model confirms the sensitivity of the supplied acoustic
      power to the liquid level in sonobioreactors and identifies the input electrical
      impedance as a method of detecting resonance effects. 

PMID- 25771445
TI  - Biomechanical evaluation of two innovative locking implants for comminuted
      olecranon fractures under high-cycle loading conditions.
AB  - INTRODUCTION: The relatively high complication rate after fixation of olecranon
      fractures has led to an increasing application of anatomically pre-contoured
      locking plate systems. The purpose of the present study was to conduct a
      biomechanical comparison of olecranon osteosyntheses by applying the Olecranon VA
      LCP and the 3.5mm LCP Hook Plate (LCP, locking compression plate) to an unstable
      fracture model under high-cycle loading conditions. METHODS: After creating an
      unstable fracture (Schatzker type B), osteosynthesis was performed on eight pairs
      of fresh-frozen cadaveric ulnae by application of either the Olecranon VA-LCP
      (Synthes, Solothurn, Switzerland) or the 3.5mm LCP Hook Plate (Synthes,
      Solothurn, Switzerland). Loading (50,000 alternating loads, cyclic and sinusoidal
      10-300 N) was conducted by application of tensile load with the elbow in 90
      degrees  flexion to simulate the tensile strength of the triceps brachii. For
      statistical analysis, angular displacement in the region of the humeral trochlea
      was taken as a measure of olecranon dislocation. RESULTS: In Group 1 (Olecranon
      VA-LCP), a median angular displacement of 0.36 degrees  (minimum 0.10 degrees ;
      maximum 0.80 degrees ) was observed after 500 alternating loads. In Group 2 (3.5
      mm LCP Hook Plate), the medial displacement was 0.80 degrees  (minimum 0.13
      degrees ; maximum 2.72 degrees ). The difference was nonsignificant (p = 0.128).
      The mean value for angular displacement in Group 1 after 50,000 cycles was 0.80
      degrees  (minimum 0.31 degrees ; maximum 1.99 degrees ), whereas in Group 2 a
      mean angular displacement of 2.02 degrees  (minimum 0.71 degrees ; maximum 6.40
      degrees ) was recorded. The difference was statistically significant (p = 0.017).
      In Group 2, implant failure in the form of proximal plate pullout occurred in one
      construct after 756 cycles. CONCLUSION: A significantly higher biomechanical
      stability can be achieved in the fixation of unstable olecranon fractures by
      application of the Olecranon VA-LCP rather than the 3.5mm LCP Hook Plate.

PMID- 25771447
TI  - Teamwork in trauma: simply being part of a team is not enough!

PMID- 25771446
TI  - Impaction bone grafting has potential as an adjunct to the surgical stabilisation
      of osteoporotic tibial plateau fractures: Early results of a case series.
AB  - INTRODUCTION: Osteoporotic tibial plateau fractures (TPFs) are difficult to treat
      with either open reduction internal fixation (ORIF) or acute total knee
      arthroplasty (TKA). They have high complication rates, poor outcomes and often
      fail in the short- to mid-term. We investigated the use of impaction bone
      grafting (IBG) as an adjunct to stabilise the fracture in a cohort of
      osteoporotic TPFs. METHODS: Nine consecutive osteoporotic TPFs were surgically
      stabilised with ORIF augmented with IBG or with IBG alone (one pure depression
      fracture) using on average allograft from 2 femoral heads/case (range 1-4 heads
      or 25-100 cm(3)). The median bone mineral density T-score of the patients was 
      2.9 (-2.5 to -4.5). All patients were mobilised weight-bearing as tolerated
      immediately after surgery and had regular follow-up to a minimum of 2 years where
      functional scores were taken and gait was assessed. Fracture reduction was
      assessed on plain radiographs and computed tomography (CT) scans; maintenance of
      fracture reduction was monitored using plain radiographs, CT and
      radiostereometric analysis (RSA). Bone graft remodelling was assessed by
      comparison of immediate post-operative CT scans with scans at a minimum of 1
      year. RESULTS: All surgeries were uneventful. All patients progressed to full
      weight bearing within 6 weeks of surgery and regained a normal gait by 3 months.
      Seven fractures healed with a cranio-caudal migration of less than 3mm (range 0
      2.6mm using RSA and 0-2mm using CT). Two fractures had an isolated posterolateral
      fragment depression of 13.5mm and 9 mm, respectively, which did not affect the
      overall joint alignment or clinical outcomes at short-term follow-up. At latest
      CT follow-up, on average 51% of the graft area (range 36-70%) had remodelled into
      new host bone. CONCLUSION: Impaction bone grafting shows promising results as an
      adjunct to the surgical stabilisation of osteoporotic TPFs. In this case series
      the technique provided enough fracture stability for patients to mobilise weight
      bearing as tolerated immediately after surgery and achieve full weight-bearing by
      the sixth postoperative week. There was no failure of fixation and 7 of the 9
      cases healed with minimal fracture displacement.

PMID- 25771448
TI  - Oligomerization-function relationship of EGFR on living cells detected by the
      coiled-coil labeling and FRET microscopy.
AB  - The epidermal growth factor receptor (EGFR) is a well-studied receptor tyrosine
      kinase and an important anticancer therapeutic target. The activity of EGFR
      autophosphorylation and transphosphorylation, which induces several cell
      signaling pathways, has been suggested to be related to its oligomeric state.
      However, the oligomeric states of EGFRs induced by EGF binding and the receptor
      ligand stoichiometry required for its activation are still controversial. In the
      present study, we performed Forster resonance energy transfer (FRET) measurements
      by combining the coiled-coil tag-probe labeling method and spectral imaging to
      quantitatively analyze EGFR oligomerization on living CHO-K1 cell membranes at
      physiological expression levels. In the absence of its ligands, EGFRs mainly
      existed as monomers with a small fraction of predimers (~10%), whereas ~70% of
      the EGFRs formed dimers after being stimulated with the ligand EGF. Ligand
      induced dimerization was not significantly affected by the perturbation of
      membrane components (cholesterol or monosialoganglioside GM3). We also
      investigated both dose and time dependences of EGF-dependent EGFR dimerization
      and autophosphorylation. The formation of dimers occurred within 20s of the
      ligand stimulation and preceded its autophosphorylation, which reached a plateau
      90 s after the stimulation. The EGF concentration needed to evoke half-maximum
      dimerization (~1 nM) was lower than that for half-maximum autophosphorylation (~8
      nM), which suggested the presence of an inactive dimer binding a single EGF
      molecule.

PMID- 25771449
TI  - Phosphorylation, nitrosation and plasminogen K3 modulation make VDAC-1 lucid as
      part of the extrinsic apoptotic pathway-Resulting thesis: Native VDAC-1
      indispensible for finalisation of its 3D structure.
AB  - Native and recombinant VDAC preparations differ in their acetylation,
      phosphorylation and nitrosation state; additionally, proteineous modulators are
      missing in the latter. They thus vary in channel characteristics, as can be taken
      from comparative black lipid bilayer experiments. Furthermore, the multi
      compartment expression makes expect even differing native VDAC-1 molecules.
      Recent structural work on mammalian VDAC-1 has only used recombinant material,
      refolded from Escherichia coli inclusion bodies. While this approach established
      the basic three-dimensional structure of VDAC-1, a beta-barrel set up by nineteen
      beta-pleated sheets, dissent is on positioning and movements of its free N
      terminal helical peptide stretch preceding beta-pleated sheet-1. A synopsis of
      data concerning posttranslational modifications, cyto-topology and physiology of
      native VDAC-1, from my point of view, suggests that the finalisation of its three
      dimensional structure will need native channel preparations to be studied.
      Concerning relevance, recent evidence on the regulation of cell membrane
      integrated VDAC-1 by posttranslational modifications and proteineous modulators,
      taken together with experimental demonstrations that VDAC-1 is involved in cell
      volume regulation, it thus may be part of the extrinsic apoptotic pathway can
      hopefully help to understand some relevant medical syndromes, e.g. cystic
      fibrosis, Alzheimer's disease, autism and malaria. 

PMID- 25771450
TI  - Biomimetic monolayer films of digalactosyldiacylglycerol incorporating
      plastoquinone.
AB  - The photosynthesis is the process used by plants and bacteria cells to convert
      inorganic matter in organic thanks to the light energy. This process consist on
      several steps, being one of them the electronic transport from the photosystem II
      to the cytochrome thanks to plastoquinone-9 (PQ). Here we prepare membranes that
      mimic the characteristics and composition of natural photosynthetic cell
      membranes and we characterize them in order to obtain the PQ molecules position
      in the membrane and their electrochemical behaviour. The selected galactolipid is
      digalactosyldiacylglycerol (DGDG) that represents the 30% of the thylakoid
      membrane lipid content. The results obtained are worthful for several science
      fields due to the relevance of galactolipids as anti-algal, anti-viral, anti
      tumor and anti-inflammatory agents and the antioxidant and free radical scavenger
      properties of prenylquinones. Both pure components (DGDG and PQ) and the DGDG:PQ
      mixtures have been studied using surface pressure-area isotherms. These isotherms
      give information about the film stability and indicate the thermodynamic
      behaviour of the mixture and their physical state. The Langmuir-Blodgett (LB)
      film has been transferred forming a monolayer that mimics the bottom layer of the
      biological membranes. This monolayer on mica has been topographically
      characterized using AFM and both the height and the physical state that they
      present have been obtained. Moreover, these monolayers have been transferred onto
      ITO that is a hydrophilic substrate with good optical and electrical features, so
      that, it is suitable for studying the electrochemical behaviour of these systems
      and it is a good candidate for energy producing devices. 

PMID- 25771451
TI  - Magnolol and honokiol regulate the calcium-activated potassium channels signaling
      pathway in Enterotoxigenic Escherichia coli-induced diarrhea mice.
AB  - To explore the regulatory mechanisms of magnolol and honokiol on calcium
      activated potassium channels signaling pathway in Enterotoxigenic Escherichia
      coli (ETEC)-induced diarrhea mice, the concentrations of serum chloride ion (Cl(
      )), sodium ion (Na(+)), potassium ion (K(+)) and calcium ion (Ca(2+)) were
      measured. Additionally, the mRNA expressions of calmodulin 1 (CaM),
      calcium/calmodulin-dependent protein kinase II alpha subunit (CaMKIIalpha) and
      beta subunit (CaMKIIbeta), ryanodine receptor 1, inositol 1,4,5-trisphosphate
      receptors (IP3 receptors), protein kinases C (PKC), potassium intermediate/small
      conductance calcium-activated channels (SK) and potassium large conductance
      calcium-activated channels(BK)were determined. A diarrhea mouse model was
      established using ETEC suspensions (3.29*10(9)CFU/ml) at a dosage of 0.02ml/g
      live body weight (BW). Magnolol or honokiol was intragastrically administered at
      dosages of 100 (M100 or H100), 300 (M300 or H300) and 500 (M500 or H500) mg/kg BW
      according to a 3*3 factorial arrangement. Magnolol and honokiol increased the Cl(
      ) and K(+) concentrations, further, upregulated the CaM, BKalpha1 and BKbeta3
      mRNA levels but downregulated the IP3 receptors 1, PKC, SK1, SK2, SK3, SK4 and
      BKbeta4 mRNA expressions. Magnolol and honokiol did not alter the CaMKIIalpha,
      CaMKIIbeta, ryanodine receptor 1, IP3 receptor 2, IP3 receptor 3, BKbeta1 and
      BKbeta2 mRNA expressions. These results clarify that magnolol and honokiol,
      acting through Ca(2+) channel blockade, inhibit the activation of IP3 receptor 1
      to regulate the IP3-Ca(2+) store release, activate CaM to inhibit SK channels,
      and effectively suppress PKC kinases to promote BKalpha1 and BKbeta3 channels
      opening and BKbeta4 channel closing, which modulates the intestinal ion
      secretion.

PMID- 25771452
TI  - The profile of mephedrone on human monoamine transporters differs from 3,4
      methylenedioxymethamphetamine primarily by lower potency at the vesicular
      monoamine transporter.
AB  - Mephedrone (4-methylmethcathinone, MMC) and 3,4-methylenedioxymethamphetamine
      (MDMA) are constituents of popular party drugs with psychoactive effects.
      Structurally they are amphetamine-like substances with monoamine neurotransmitter
      enhancing actions. We therefore compared their effects on the human monoamine
      transporters using human cell lines stably expressing the human noradrenaline,
      dopamine and serotonin transporter (NET, DAT and SERT); preparations of synaptic
      vesicles from human striatum in uptake experiments; and a superfusion system
      where releasing effects can be reliably measured. MMC and MDMA were equally
      potent in inhibiting noradrenaline uptake at NET, with IC50 values of 1.9 and 2.1
      uM, respectively. Compared to their NET inhibition potency, both drugs were
      weaker uptake inhibitors at DAT and SERT, with MMC being more potent than MDMA at
      DAT (IC50: 5.9 vs 12.6 uM) and less potent than MDMA at SERT (IC50: 19.3 vs 7.6
      uM). MMC and MDMA both induced concentration-dependently [(3)H]1-methyl-4
      phenylpyridinium-release from NET-, DAT or SERT-expressing cells which was
      clearly transporter-mediated release as demonstrated by the selective inhibitory
      effects of nmolar to low umolar concentrations of desipramine, GBR 12909 and
      fluoxetine, respectively. MMC and MDMA differed most in their inhibition of
      [(3)H]dopamine uptake by synaptic vesicles from human striatum with MDMA being 10
      fold more potent than MMC (IC50: 20 vs 223 uM) and their ability to release
      [(3)H]dopamine from human vesicular monoamine transporter expressing SH-SY5Y
      neuroblastoma cells in which MDMA seems to have a stronger effect. Our findings
      give a molecular explanation to the lower long-term neurotoxicity of MMC compared
      to MDMA.

PMID- 25771453
TI  - Suppression of Ca(2+) influx in endotoxin-treated mouse cerebral cortex
      endothelial bEND.3 cells.
AB  - Release of nitric oxide (NO) is triggered by a rise in endothelial cell (EC)
      cytosolic Ca(2+) concentration ([Ca(2+)]i) and is of prime importance in vascular
      tone regulation as NO relaxes vascular smooth muscle. Agonists could stimulate EC
      [Ca(2+)]i elevation by triggering Ca(2+) influx via plasma membrane ion channels,
      one of which is the store-operated Ca(2+) channel; the latter opens as a result
      of agonist-triggered internal Ca(2+) release. Endotoxin (lipopolysaccharide, LPS)
      could cause sepsis, which is often the fatal cause in critically ill patients.
      One of the LPS-induced damages is EC dysfunction, eventually leading to
      perturbations in hemodynamics. We obtained data showing that LPS-challenged mouse
      cerebral cortex endothelial bEND.3 cells did not suffer from apoptotic death, and
      in fact had intact agonist-triggered intracellular Ca(2+) release; however, they
      had reduced store-operated Ca(2+) entry (SOCE) after LPS treatment for 3h or
      more. Using real-time PCR, we did not find a decrease in gene expression of
      stromal interaction molecule 1 (STIM1) and Orai1 (two SOCE protein components) in
      bEND.3 cells treated with LPS for 15h. LPS inhibitory effects could be largely
      prevented by sodium salicylate (an inhibitor of nuclear factor-kappaB; NF-kappaB)
      or SB203580 (an inhibitor of p38 mitogen-activated protein kinases; p38 MAPK),
      suggesting that the p38 MAPK-NF-kappaB pathway is involved in SOCE inhibition.

PMID- 25771454
TI  - Antihyperalgesic and antiallodynic effects of mianserin on diabetic neuropathic
      pain: a study on mechanism of action.
AB  - This study used various experimental pain methods to investigate the effects of
      subacute mianserin administration on diabetes-induced neuropathic pain in rats.
      The effect of mianserin on hyperalgesia occurring in connection with peripheral
      diabetic neuropathy was examined using the Randall-Selitto (mechanical
      nociceptive stimulus), Hargreaves (thermal nociceptive stimulus), and cold-plate
      (4 degrees C, thermal nociceptive stimulus) tests. The dynamic plantar
      aesthesiometer, which measures the threshold values for mechanical stimuli, was
      used for allodynia studies. Thermal allodynia was evaluated with the warm-plate
      (38 degrees C) test. At 30 and 45 mg/kg, mianserin effectively improved
      mechanical and thermal hyperalgesia occurring in connection with diabetic
      neuropathy. Subacute administration of mianserin also reduced diabetes-associated
      mechanical and thermal allodynia. The ability of mianserin to reduce diabetic
      neuropathic pain was comparable to that of pregabalin (10mg/kg). The
      antihyperalgesic and antiallodynic effects of mianserin were reversed with alpha
      methyl-para-tyrosine methyl ester (AMPT, an inhibitor of catecholamine
      synthesis), phentolamine (a non-selective alpha-adrenoceptor antagonist),
      propranolol (a non-selective beta-adrenoceptor antagonist), and naloxone (a non
      selective opioid receptor antagonist) administrations. The same effects were not
      reversed, however, by para-chlorophenylalanine methyl ester (PCPA; an inhibitor
      of serotonin synthesis). These results suggest that the beneficial effect of
      mianserin on diabetic neuropathic pain is mediated through an increase in
      catecholamine levels in the synaptic cleft as well as through interactions with
      both subtypes of adrenoceptors and opioid receptors. Considering that mianserin
      exhibits simultaneous antidepressant and antinociceptive effects, this drug could
      provide a good alternative for treating the pain associated with diabetic
      neuropathy and the mood disorders caused directly by diabetes.

PMID- 25771455
TI  - Clozapine and olanzapine inhibit proton currents in BV2 microglial cells.
AB  - Excessive reactive oxygen species produced by NADPH oxidase in over-activated
      microglia can lead to neuronal death. Some atypical antipsychotic drugs possibly
      have anti-inflammatory properties and suppress the production of pro-inflammatory
      cytokines and reactive oxygen species from microglia. Voltage-gated proton
      channels (Hv1) are expressed in microglia and are required for NADPH oxidase
      dependent reactive oxygen species generation, which could contribute to neuronal
      death and ischemic brain damage. In the present study, we examined the effects of
      the atypical antipsychotics clozapine, olanzapine and risperidone on proton
      currents in microglial BV2 cells. Clozapine and olanzapine inhibited proton
      currents with IC50 values of 9.8 MUM and 84 MUM, respectively. Risperidone,
      however, showed very weak inhibition of proton currents. Clozapine-induced
      inhibition of proton currents was not accompanied by a positive shift in the
      activation voltage or reversal potential, indicating that the inhibition was not
      mediated through an increase in the intracellular pH. Clozapine binds to a
      multitude of receptors, including serotonin, dopamine and muscarinic receptors.
      Serotonin receptors, however, were not responsible for the proton current
      inhibition by clozapine. Of the three drugs, only clozapine could reach
      concentrations to inhibit microglial proton currents in the brain at therapeutic
      doses. Thus, the anti-inflammatory activity of clozapine may be partly
      attributable to its inhibition of microglial proton currents.

PMID- 25771456
TI  - Regulation of nicotinic acetylcholine receptors in Alzheimer's disease: a
      possible role of chaperones.
AB  - Nicotinic acetylcholine receptors (nAChRs) seem to play an integral role in the
      progress and/or prevention of Alzheimer's diseases (AD). Functional abnormalities
      and problems in biogenesis and trafficking of nAChRs are two major culprits in
      AD; on the other hand, chaperones modulate post-translational changes in nAChRs.
      Moreover, they indirectly regulate nAChRs by controlling AD-related proteins such
      as tau and amyloid beta (Abeta). In this review, we go through recent studies
      which are showing that chaperones modulate the expression of nAChRs in a subtype
      specific manner and explain how AD progress is affected by nAChRs chaperoning.

PMID- 25771457
TI  - Ghrelin ameliorates catabolic conditions and respiratory dysfunction in a chronic
      obstructive pulmonary disease model of chronic cigarette smoke-exposed rats.
AB  - Cigarette smoking, which is a well-known major risk factor for chronic
      obstructive pulmonary disease (COPD), causes both pulmonary and extrapulmonary
      abnormalities. Ghrelin is a gastric peptide that regulates energy homeostasis. In
      the present study, we investigated the effects of ghrelin on the catabolic
      changes, respiratory function and emphysema in an animal model of COPD induced by
      chronic exposure to cigarette smoke. Rats were exposed to cigarette smoke, and
      they were administered human ghrelin (0.1 or 1 mg/kg, subcutaneous, twice daily)
      for 12 weeks. Compared with air-exposed rats, body weight gain, food intake, food
      efficiency, tidal volume, peak expiratory flow rate, and forced expiratory volume
      at 100 ms were significantly lower, while functional residual capacity, lung
      capacity, and neutrophils in bronchoalveolar lavage fluid were significantly
      higher in cigarette smoke-exposed rats. These indicated that the systemic
      abnormalities associated with COPD developed after the exposure to cigarette
      smoke. Ghrelin significantly and dose-dependently increased the body weight gain
      and food efficiency in cigarette smoke-exposed rats. In ghrelin-treated rats,
      skeletal muscle strength, which tended to be lowered by cigarette smoke exposure,
      was improved. Ghrelin ameliorated respiratory function and emphysema in a dose
      dependent manner, but did not inhibit the increase in neutrophils in the
      bronchoalveolar lavage fluid. The respiratory functional parameters and lung
      capacity were significantly correlated with body weight gain. These results
      suggest that ghrelin inhibited the development of the catabolic changes,
      respiratory dysfunction, and emphysema that were induced by cigarette smoke
      exposure in rats, at least in part, through the amelioration of nutritional
      status.

PMID- 25771458
TI  - Tuberculosis in Saudi Arabia: the journey across time.
AB  - Saudi Arabia is the third-largest Arab country with a moderate annual burden of
      tuberculosis. However, tuberculosis (TB) is among several infectious diseases
      that have not been brought under control, despite the government's considerable
      efforts. This is clearly evidenced by the ongoing transmission of several
      imported and indigenous clades of Mycobacterium tuberculosis. In addition, the
      country faces the threat from rising proportions of extrapulmonary TB, non
      tuberculous mycobacterial infections, and drug resistance. Furthermore, the
      country falls behind the global targets set by World Health Organization for the
      success rate of TB treatment. The country needs more population-based research
      studies, centralized and easily accessible clinical data registries, and
      centralized research and diagnostic facilities. This review focused on the trends
      of mycobacterial infections and on future proposals to improve TB control
      measures in Saudi Arabia.

PMID- 25771459
TI  - Clinical variables associated with disability in leprosy cases in northeast
      Brazil.
AB  - INTRODUCTION: The clinical outcomes of leprosy include complications such as
      physical disabilities and deformities that vary according to the degree of
      impairment of nerve trunks. Knowledge of the factors that lead to the development
      of these complications is important for disability prevention programs. This
      study aimed to evaluate clinical factors associated with the occurrence of
      physical disability in leprosy cases. METHODOLOGY: This was a retrospective study
      of 2,358 cases of leprosy in Aracaju, northeast Brazil, between 2001 and 2011.
      Analysis was done using the Chi-square test and logistic regression model.
      RESULTS: Significant factors associated with disability were found to be male
      gender, having more than two affected nerves, multibacillary leprosy
      classification, leprosy reaction, and lepromatous leprosy. The multivariate
      analysis revealed that the associated factors included having more than two
      affected nerves, leprosy reaction (adjusted odds ratio [aOR]: 2.02, 95%
      confidence interval [CI]: 1.36 to 3.01), the multibacillary form (aOR: 2.74, 95%
      CI: 1.84 to 4.08), and lepromatous leprosy (aOR: 4.87, 95% CI: 2.86 to 16.08).
      CONCLUSIONS: The number of affected nerves, leprosy reaction, operational
      classification, and clinical presentation were identified as the main factors
      associated with the development of disability in leprosy patients.

PMID- 25771460
TI  - Assessment of Brazilian pharmacists' knowledge about antimicrobial resistance.
AB  - INTRODUCTION: Antimicrobial resistance (AR) is a multifaceted problem of global
      significance. In addition to developing new drugs and using antimicrobial
      guidelines, it is essential that health professionals understand all aspects of
      the problem and the most effective ways to handle it. This study evaluated
      pharmacists' level of knowledge about bacterial resistance and antibiotic use in
      Brazil. METHODOLOGY: The study was conducted using a survey provided
      electronically to pharmacists in Sao Paulo State, Brazil. RESULTS: In total, 754
      pharmacists completed the survey. The majority of the pharmacists were young
      (under 30 years of age), female, and worked in community pharmacies. Pharmacists
      who worked in hospital or community pharmacies reported a greater AR interference
      in their work than did pharmacists working in other locations (p < 0.05). With
      respect to factors that contribute to AR, pharmacists placed little weight on the
      role of inadequate hand washing or lack of immunization campaigns. The
      pharmacists also believed that vaccination was of limited value in combating AR
      and instead placed the highest value on educational campaigns. The study showed
      that pharmacists who used package inserts and advertising material as their
      source for updated information had a poorer understanding of the appropriate use
      of antibiotics than did those who obtained their information from scientific
      journals, textbooks, or scientific meetings. CONCLUSIONS: The results highlight
      the need for adequate information regarding AR to reach health professionals such
      as pharmacists. Governments should promote campaigns for integrated actions to
      combat the serious global problem presented by AR.

PMID- 25771461
TI  - Comparison of P1 and 16S rRNA genes for detection of Mycoplasma pneumoniae by
      nested PCR in adults in Zhejiang, China.
AB  - INTRODUCTION: Mycoplasma pneumoniae (M. pneumoniae) is the most common atypical
      pathogen that causes respiratory infections in humans. Laboratory tests are
      important in the diagnosis of M. pneumoniae because of the atypical features in
      clinical signs and symptoms. Nowadays, both the P1 adhesin gene and 16S ribosomal
      (r) RNA (rRNA) gene of M. pneumoniae have been widely detected by polymerase
      chain reaction (PCR). The purpose of the present study was to evaluate the most
      suitable target in the detection of M. pneumonia via nested PCR. METHODOLOGY:
      Both the P1 adhesin gene and 16S rRNA gene for nested PCR reaction conditions
      were optimized through an orthogonal test and single-factor experiment. Then, the
      sensitivity of the two sets of targets was evaluated. Finally, based on the
      optimal conditions, 55 clinical samples of throat swabs collected from adult
      patients in 2013 were examined by established nested PCR. RESULTS: The results
      revealed that PCR detection of the 16S rRNA gene was more sensitive than the P1
      adhesin gene because the detection limits for both the P1 gene and 16S rRNA gene
      were at least 100 fg and 10 fg of M. pneumoniae DNA, respectively. Furthermore,
      the positive rate for detection of the 16S rRNA gene (30/55; 54.5%) was higher
      than that of the P1 adhesin gene (25/55; 45.5%). CONCLUSION: Our results indicate
      that the 16S rRNA gene is more suitable for diagnosis of M. pneumoniae infection
      than the P1 adhesin gene due to its higher sensitivity and positive rate in
      clinical samples.

PMID- 25771462
TI  - Seroprevalence of hepatitis A,B, and C viruses in Turkish alcoholic cirrhotics
      and the impact of hepatitis B on clinical profile.
AB  - INTRODUCTION: The aims of this study were to detect the seroprevalence of
      hepatitis A, B, and C viruses in Turkish alcoholic cirrhotics, and to evaluate
      the impact of hepatitis B infection on clinical profile at first admittance.
      METHODOLOGY: Serological markers for hepatitis A, B, and C viruses in 300
      alcoholic cirrhotics diagnosed between January 1994 and December 2012 were
      retrospectively reviewed. Among them, 148 eligible patients were divided into
      group 1 (HBsAg positive, n = 43) and group 2 (HBsAg and anti-HBc negative, n =
      105). Clinical characteristics at first admittance of groups 1 and 2 were
      compared. RESULTS: The seroprevalence of anti-HAV total, HBsAg, and anti-HCV was
      found to be 91.5%, 16.3%, and 8.2%, respectively. The prevalence of
      hepatocellular carcinoma was higher in the HbsAg-positive group compared to HbsAg
      and anti-HBc-negative group (16.3% vs. 2.9%, p = 0.007). Other clinical features
      were similar in the two groups. CONCLUSIONS: Alcoholic cirrhotics have higher
      frequencies of HBsAg and anti-HCV than the general population. These patients
      should be investigated for coexistent HBV and HCV infections, and HBV vaccination
      should not be neglected. Alcoholic cirrhotic patients with concomitant HBV
      infection should be closely screened for hepatocellular carcinoma.

PMID- 25771463
TI  - Antibody responses to influenza viruses in paediatric patients and their contacts
      at the onset of the 2009 pandemic in Mexico.
AB  - INTRODUCTION: On April 2009, the Mexican Ministry of Health received notification
      of cases of severe pneumonia mostly affecting young healthy people; this was the
      beginning of the first influenza pandemic of the 21st century. The nature of the
      immune response to the influenza A(H1N1)2009 pandemic strain in Mexico at the
      beginning of the pandemic outbreak has not been completely defined. We describe
      the serological response to the 2009 pandemic influenza virus in paediatric
      patients with influenza-like illness, their household contacts (HHCs), and
      exposed health-care workers (HCWs) at the beginning of the pandemic outbreak in
      Mexico City. METHODOLOGY: thirty pre-epidemic and 129 epidemic samples were
      collected and serum antibodies were measured against A(H1N1)2009 pandemic virus
      and two non-pandemic swine influenza viruses by an haemagglutination inhibition
      assay . RESULTS: 91% (29/32) of the convalescence samples from confirmed patients
      had an antibody titre >= 10 (GMT 25), 63% (41/65) of the HHCs (GMT 12), 41% of
      HCWs (GMT 6) and 13% (4/30) of pre-epidemic samples (GMT 6) for the pandemic
      influenza virus. Of the 32 confirmed cases, 60% had an antibody titre >= 40 for
      the pandemic strain, 53% for the A/swine/Iowa(H1N1) virus (GMT 62) and 43% for
      the A/swine/Texas(H3N2) virus (GMT 66). CONCLUSION: The antibody response to 2009
      pandemic influenza virus was widespread in convalescence samples from patients
      with confirmed pandemic influenza infection but the GMT was below the protective
      titre. There was no evidence that antibodies to the swine influenza viruses had
      cross-protective effect against the 2009 pandemic influenza virus.

PMID- 25771464
TI  - Responses to peginterferon alfa-2a vs alfa-2b plus ribavirin in a Mexican
      population with chronic hepatitis C.
AB  - INTRODUCTION: The WHO estimates that 180 million people are chronically infected
      with hepatitis C virus (HCV) throughout the world. Despite the emergence of new
      therapies, the combination of pegylated interferon and ribavirin remains the
      accepted standard of care in low-income countries, including Mexico. Two types of
      peginterferon are available (peginterferon alfa-2a and peginterferon alfa-2b),
      and both are recommended for the treatment of HCV, although there is controversy
      over which treatment option is most effective. METHODOLOGY: This was a
      retrospective cohort study at a infectious disease center in Mexico City.
      Patients were included if they had received peginterferon alfa-2a or
      peginterferon alfa-2b plus ribavirin. Age, sex, body mass index, AST platelet
      ratio index, HCV RNA viral load, levels of alanine aminotransferase, aspartate
      aminotransferase, bilirubin, albumin, and hemoglobin, and platelet and leukocyte
      counts of the subjects were assessed before treatment and at weeks 4, 12, 24, 48,
      and 6 months post treatment. RESULTS: Eighty-seven patients met the inclusion
      criteria. A sustained virological response (SVR) occurred in 33 (38%) of them, 11
      (33%) given peginterferon alfa-2a and 22 (67%) given peginterferon alfa-2b (p =
      0.17). Seventeen patients (20%) relapsed, 7 (41%) of those given peginterferon
      alfa-2a and 10 (59%) of those given peginterferon alfa-2b (p = 0.76); 27 (31%)
      patients were non-responders (p = 0.09). The rates of anemia, thrombocytopenia,
      and leukopenia were similar in both groups. CONCLUSIONS: Similar SVR rates and
      frequencies of adverse events were observed. Either type of interferon can be
      used to treat HCV infection in the Mexican population.

PMID- 25771465
TI  - Seroprevalence of hepatitis viruses and risk factors in blood donors of Veracruz,
      Mexico.
AB  - INTRODUCTION: Hepatitis B and C are among the most important transfusion
      transmitted infections and sources of liver diseases worldwide. In Veracruz,
      Mexico, liver diseases are important causes of mortality, and the prevalence
      reports of these viruses are scarce. This study sought to determine the
      prevalence of these infections in blood donors, in order to increase the safety
      of blood products in this region. METHODOLOGY: A retrospective study was
      performed on blood donors who attended the Veracruz State Blood Transfusion
      Center from 2006 to 2010. All samples were screened for transfusion-transmitted
      infections. The prevalence rates of hepatitis B virus (HBV) and hepatitis C virus
      (HCV) were determined, and demographic data obtained from clinical records were
      used to evaluate risk factors. RESULTS: A total of 56,377 donors were
      serologically screened; of them, 403 were seropositive for HCV (357 men and 46
      women), and 61 were positive for HBsAg (52 men and 9 women). The overall
      prevalence rates were 0.72% (0.63%-0.76%) for HCV and 0.11% (0.08%-0.14%) for
      HBsAg. The risk factors for HBsAg positivity were being a cattleman and living in
      the Huasteca Baja region, whereas those for HCV were being a fisherman, living in
      the Papaloapan region, and having an elementary-level or lower education.
      CONCLUSIONS: This is the first study to show that being a fisherman is a risk
      factor for HCV. The implementation of nucleic acid test technology will help to
      identify the real risks for transfusion-transmitted hepatitis C in Veracruz.

PMID- 25771466
TI  - Hematological and serum biochemical findings in clinical cases of cattle
      naturally infected with lumpy skin disease.
AB  - INTRODUCTION: Lumpy skin disease (LSD) is an acute viral disease of cattle that
      is currently emerging in the Middle East region and poses a serious threat to
      Europe and the rest of the world. The objective of this study was to describe
      hematological and serum biochemical findings associated with natural clinical
      infection of LSD in cattle. METHODOLOGY: A total of 129 animals clinically
      infected with LSD were enrolled in the study. Venous blood sample were collected
      from study animals, and hematological and serum biochemical parameters were
      measured. RESULTS: Leukocytopenia was found in 8.7%, while leucocytosis was found
      in 18.2% of affected cattle. Decreased hematocrit concentration was seen in
      18.3%. Most affected cattle had reduced mean corpuscular volume (43.7%), mean
      corpuscular hemoglobin (14.3%), and mean corpuscular hemoglobin concentration
      (11.5%). All cattle with abnormal platelets count had thrombocytopenia.
      Hyperfibrinogenemia, hyperproteinemia, and hyperalbuminemia were found in 69%,
      59.6%, and 37.2% of affected cattle, respectively. Decreased creatinine
      concentration was seen in 65.8%. Hyperkalemia and hyperchloremia was found in
      9.6% and 10.4% of the affected cattle, respectively. CONCLUSIONS: LSD appears to
      be associated with inflammatory leukogram, anemia, thrombocytopenia,
      hyperfibrinogenemia, hyperproteinemia, decreased creatinine concentration,
      hyperchloramia, and hyperkalemia. These are likely due to the associated severe
      inflammatory process and disease complications such as anorexia and reduced
      muscle mass. This is the first study that documents hematological and serum
      biochemical findings associated with LSD infection. Understanding the blood
      profile picture may give further insight to the pathogenesis of the disease and
      help in treatment of individual cattle.

PMID- 25771467
TI  - Prevalence of glucose-6-phosphate dehydrogenase (G6PD) deficiency in southeast
      Iran: implications for malaria elimination.
AB  - INTRODUCTION: Glucose-6-phosphate dehydrogenase deficiency (G6PD) is an X-linked
      genetic disorder with a relatively high frequency in malaria-endemic regions. It
      is an obstacle to malaria elimination, as primaquine administered in the
      treatment of malaria can cause hemolysis in G6PD-deficient individuals. This
      study presents information on the prevalence of G6PD deficiency in Sistan and
      Balouchetsan province, which hosts more than 90% of Plasmodium vivax malaria
      cases in Iran. This type of information is needed for a successful malaria
      elimination program. METHODOLOGY: A total of 526 students were randomly recruited
      through schools located in southeast Iran. Information was collected by
      interviewing the students using a structured questionnaire. Blood samples taken
      on filter papers were examined for G6PD deficiency using the fluorescent spot
      test. RESULTS: Overall, 72.8% (383/526) of the subjects showed normal G6PD enzyme
      function. Mild and severe G6PD deficiency was observed in 14.8% (78) and 12.2%
      (64) of subjects, respectively. A total 193/261 males (73.9%) and 190/265 (72%)
      females had normal enzyme activity. Mild G6PD deficiency was observed in 10.8%
      (28) and 18.9% (50) of male and female subjects, respectively. However, in
      comparison with females, a greater proportion of males showed severe enzyme
      deficiency (15.3% versus 9.1%). All these differences were statistically
      significant (p < 0.006). CONCLUSIONS: G6PD deficiency is highly prevalent in
      southeast Iran. G6PD-deficient individuals are susceptible to potentially severe
      and life-threatening hemolytic reactions after primaquine treatment. In order to
      achieve malaria elimination goals in the province, G6PD testing needs to be made
      routinely available within the health system.

PMID- 25771468
TI  - Phenotypic and molecular characterization of HA-MRSA in Taif hospitals, Saudi
      Arabia.
AB  - INTRODUCTION: Methicillin-resistant S. aureus (MRSA) is one of the most important
      organisms causing hospital-acquired infections worldwide. Molecular analysis of
      MRSA strains from Taif, Saudi Arabia, had not been previously done. Phenotypic
      and molecular characteristics of MRSA isolated from Taif hospitals were
      investigated. METHODOLOGY: This study involved S. aureus strains isolated from
      different clinical samples from Taif hospitals. MRSA strains were identified and
      antimicrobial susceptibility profiles were determined. Multiplex polymerase chain
      reaction (PCR) was used to identify S. aureus-specific sequence, mecA genes, and
      type of staphylococcal cassette chromosome mec (SCCmec). MRSA strains were typed
      using coagulase gene polymorphism. RESULTS: In total, 390 strains of S. aureus
      were isolated, and 58 MRSA strains - 40 hospital-acquired MRSA (HA-MRSA) and 18
      community-acquired MRSA (CA-MRSA) - were detected. HA-MRSA strains included three
      SCCmec types, while CA-MRSA strains included two SCCmec types. PCR amplification
      and restriction of the coagulase gene of the 58 MRSA isolates showed nine
      different patterns, while three strains were non-typable. HA-MRSA strains showed
      seven distinct restriction fragment length polymorphism (RFLP) patterns; the most
      frequent was pattern 2 (15 isolates), followed by patterns 1 and 4 (5 isolates
      each). CA-MRSA showed five RFLP patterns; the most frequent was pattern 3 (7
      isolates) followed by pattern 8 (6 isolates). CONCLUSIONS: HA-MRSA strains were
      more common than CA-MRSA strains. SCCmec typing and coagulase gene polymorphism
      analysis may be useful methods for studying clonal relatedness of isolates and
      for discriminating between HA-MRSA and CA-MRSA.

PMID- 25771469
TI  - Fecal carriage of extended-spectrum beta-lactamase- and AmpC- producing
      Escherichia coli among healthcare workers.
AB  - INTRODUCTION: Commensal E. coli can be considered a reservoir of genes coding for
      antibiotic resistance that may be transmitted in hospitals by healthcare workers
      (HCWs). This study aimed to determine the fecal carriage rate of extended
      spectrum beta-lactamase (ESBL)-producing E. coli among HCWs. METHODOLOGY: Stool
      samples were collected from 200 HCWs. Phenotypic screening for ESBL and AmpC beta
      lactamases was performed using disk diffusion and minimum inhibitory
      concentration methods followed by the combined disks test and double synergy
      differential test for confirmation. Multiplex polymerase chain reaction (PCR) was
      used to detect blaSHV, blaTEM, blaCTX-M, and CIT groups for AmpC genes. RESULTS:
      Of 200 E. coli isolates, 100% were susceptible to imipenem, and 59 (29.5%) were
      resistant to one or more third-generation cephalosporins. By molecular analysis,
      21% (42/200) were colonized by ESBL-producing E. coli, and 3% (6/200) were
      colonized by AmpC-producing E. coli. The blaSHV gene was the predominant ESBL
      gene, detected in 81.8% of the resistant E. coli isolates. CONCLUSIONS: These
      findings highlight the increase in fecal carriage of E. coli carrying ESBL and
      AmpC genes among HCWs, which may be one of the causes of the spread of ESBL
      producing bacteria in hospitals and requires sound infection control measures.
      This is the first study of the fecal carriage rate of E. coli carrying AmpC genes
      in HCWs.

PMID- 25771470
TI  - Increasing frequency of Pseudomonas aeruginosa infections during tigecycline use.
AB  - INTRODUCTION: The widespread use of tigecycline raises the question of increasing
      infection rates of Pseudomonas aeruginosa (PA) in ICUs which are not affected by
      this antibiotic. OBJECTIVE: The aim of this study was to determine if treatment
      with tigecycline is a risk factor for PA infection in ICU patients. METHODOLOGY:
      A retrospective and observational study was conducted at Erciyes University
      Hospital, Turkey, between 2008 and 2010. The Erciyes University Hospital is a
      1300-bed tertiary care facility. The patients included in this study were
      hospitalized in four adult ICUs. Patients with PA infections (case group) were
      compared with patients with nosocomial infection other than PA (control group).
      RESULTS: A total of 1,167 patients with any nosocomial infections were included
      in the study. Two hundred and seventy eight (23.8%) of the patients had PA
      infection during their ICU stay. Fifty nine patients (21.2%) in the case group
      received tigecycline before developing PA infections, which were found to be
      significantly more frequent than in the controls (p < 0.01). Multivariate
      analysis showed that risk factors for PA infection were previous tigecycline use
      (4 times), external ventricular shunt (4.2 times), thoracic drainage catheter
      (2.5 times) and tracheostomy (1.6 times). CONCLUSION: Our results contribute to
      the need for new studies to determine the safety of tigecycline use, especially
      for the treatment of critically ill patients. Since tigecycline seems to be an
      alternative for the treatment of multidrug resistant (MDR) microorganisms,
      rational use of this antibiotic in ICU patients is essential.

PMID- 25771471
TI  - First report of cervicofacial lymphadenitis due to Mycobacterium haemophilum in
      an immunocompromised adult patient.
AB  - We report the first case of an immunocompromised adult patient presenting with
      cervicofacial lymphadenitis due to Mycobacterium haemophilum, confirmed using
      hsp65 gene sequencing and line-probe assays. In resource-limited settings,
      especially in developing countries, appropriate culture methods and rapid
      molecular diagnostic tools such as hsp65 gene sequencing for identification of
      this organism may not be readily available. This may cause M. haemophilum
      infections to go unrecognised or lead to delays in diagnosis. Lack of heightened
      awareness about the potential for this mycobacterial species to cause infections
      may also contribute to possible underestimation of M. haemophilum cases in the
      developing world. 

PMID- 25771472
TI  - A case of human infection with avian Influenza A/H7N9 virus in Beijing:
      virological and serological analysis.
AB  - This study described some essential viral and sera-characteristics of A/H7N9
      virus infection in a 61-year old case patient. With the antiviral therapy and
      respiratory support, the patient showed a significant decrease of viral loads
      from 6.72 log10 copies/mL to 0 in 22 days, and a correlated increase of serum
      hemagglutination inhibition titers during the same period. Phylogenetic analysis
      demonstrated that the isolated strain was highly homologous to previous strains
      isolated in the southeast of China. Drug resistance-associated R292K mutation
      became detectable 17 days after antiviral therapy, but no remarkable influence on
      the viral clearance was observed.

PMID- 25771473
TI  - Prozone-like phenomenon in travellers with fatal malaria: report of two cases.
AB  - Malaria diagnosis remains a concern in non-endemic countries, with rapid
      diagnosis being crucial to improve patients' outcome. Rapid diagnostic tests have
      high sensitivity but they also have flaws and false-negative results that might
      jeopardize malaria diagnosis. Some false-negative results might relate to a
      prozone-like effect. The authors describe two patients with false-negative rapid
      diagnostic tests in which a prozone-like effect might have been involved. The
      authors highlight that these tests should not be used without accompanying light
      microscopy observation of blood films and discuss potential benefits of using
      rapid diagnostic tests with more than one specific antigen for Plasmodium
      falciparum. 

PMID- 25771474
TI  - Chromoblastomycosis due to Fonsecaea pedrosoi: an old wine in a rare bottle.
AB  - Chromoblastomycosis is a chronic subcutaneous mycosis commonly caused by
      Fonsecaea, Phialophora, and Cladophialophora spp. Out of these, Fonsecaea
      pedrosoi is the most common etiological agent, implicated in 70%-90% of the cases
      reported worldwide. The histopathological diagnosis of chromoblastomycosis is
      based on visualization of medlar or sclerotic bodies in the tissue. These
      sclerotic bodies divide by planar division. Rarely, budding is seen in these
      sclerotic bodies. As this entity can be confused with phaeohyphomycosis, it is
      important to be aware of such a presentation also. We report two cases of
      chromoblastomycosis that showed budding sclerotic bodies. 

PMID- 25771475
TI  - Healthcare students and workers' knowledge about epidemiology and symptoms of
      chikungunya fever in two cities of Colombia.

PMID- 25771476
TI  - Classification of Calcaneal Spurs and Their Relationship With Plantar Fasciitis.
AB  - Calcaneal spurs, as a cause of plantar fasciitis, are currently debatable. A
      prospective study was performed to classify calcaneal spurs according to the
      findings from an investigation of the relationship between calcaneal spurs and
      plantar fasciitis. Thirty patients with calcaneal spurs and plantar heel pain
      underwent calcaneal spur removal and endoscopic plantar fasciotomy. The
      relationship between the classification of calcaneal spurs and plantar fasciitis
      was evaluated by endoscopic findings, clinical symptoms, radiographic images, and
      biopsy findings. The visual analog scale for pain and the American Orthopedic
      Foot and Ankle Society ankle-hindfoot scores for functional evaluation were used
      preoperatively and postoperatively, respectively. The mean follow-up period was
      24 months. Two separate types of calcaneal spurs were recognized. Type A
      calcaneal spurs were located superior to the plantar fascia insertion, and type B
      calcaneal spurs were located within the plantar fascia. Magnetic resonance
      imaging results showed a more severe plantar fasciitis grade in type B calcaneal
      spurs preoperatively. Histologic examination showed that the numbers of
      granulocytes per image in type B spurs were significantly increased compared with
      those in type A spurs. Statistically significant improvements were found in the
      mean visual analog scale and American Orthopedic Foot and Ankle Society scores
      and magnetic resonance imaging results in both groups. The amount of change in
      the visual analog scale score and American Orthopedic Foot and Ankle Society
      score, the number of granulocytes per image, and calcaneal spur length showed a
      high association with the classification of the calcaneal spurs. Calcaneal spurs
      were completely removed and did not recur in any of the patients on radiographic
      assessment during the follow-up period. Calcaneal spurs can be classified into 2
      distinct types that are indicative of the severity of plantar fasciitis.

PMID- 25771477
TI  - Major complications due to transjugular liver biopsy: Incidence, management and
      outcome.
AB  - PURPOSE: The purpose of this study was to retrospectively evaluate the incidence
      of intraperitoneal bleeding and other major complications of transjugular liver
      biopsy (TJLB) and analyze their outcome and management. MATERIALS AND METHODS:
      The clinical files of 341 consecutive patients who had TJLB were retrospectively
      analyzed. There were 237 men and 104 women (mean age: 51.38+/-12.8 years; range:
      17-89 years). All patients had TJLB because standard percutaneous transhepatic
      biopsy was contraindicated. Patients' files were reviewed to search for major and
      minor procedure-related complications during or immediately after TJLB. RESULTS:
      TJLBs were technically successful in 331/341 patients (97.07%; 95%CI: 94.67
      98.58%). Major complications consisted exclusively of intraperitoneal bleeding
      due to liver capsule perforation and were observed in 2/341 patients (0.59%;
      95%CI: 0.07-2.10%). They were treated using transcatheter arterial or venous
      embolization with a favorable outcome. The most frequent minor complications were
      abdominal pain (35/341; 10.26%; 95%CI: 7.25-13.99%) and supraventricular
      arrhythmia (15/341; 4.40%; 95%CI: 2.48-7.15%). No cases of inadvertent injury of
      the carotid artery were observed. CONCLUSION: Major complications during TJLB are
      extremely rare and can be managed using arterial or venous embolization with a
      favorable outcome. Our results reinforce the general assumption that TJLB is a
      safe and well-tolerated technique.

PMID- 25771478
TI  - Sesamoid disorders of the hand.

PMID- 25771479
TI  - A systematic review of utilities in hand surgery literature.
AB  - PURPOSE: To systematically review the literature to determine if utilities (a
      quantitative way to express patient preferences for health outcomes) have been
      measured in hand surgery studies. METHODS: A literature search was conducted
      using Cochrane, EMBASE, HealthSTAR, MEDLINE, and CINAHL electronic databases
      (1966-2013). This search was supplemented by cited and manual reference searches
      and expert consultation to retrieve all relevant studies. Studies were selected
      by 2 independent reviewers if they pertained to hand or wrist surgery, were
      published in English, and measured utilities as an outcome. Descriptive data were
      extracted, including the hand surgery procedure investigated, study design, value
      of utilities, and methodology of utilities measurement. RESULTS: Eleven studies
      were included after reviewing 989 studies. Most hand conditions were associated
      with utilities less than 0.8. Utilities in the reviewed studies were measured
      using different methods and from different subjects. Three studies paradoxically
      mapped greater utilities for poorer heath states. CONCLUSIONS: Hand conditions
      cause impairment, as evidenced by their utilities. Measurement of utilities
      remains uncommon in hand surgery literature. Future studies should not only
      measure utilities but also do so with consistent and appropriate methodology to
      ensure that mapped values are valid and comparable. TYPE OF STUDY/LEVEL OF
      EVIDENCE: Economic/decision analysis III.

PMID- 25771480
TI  - Treatment of proximal interphalangeal joint flexion contracture: combined static
      and dynamic orthotic intervention compared with other therapy intervention: a
      randomized controlled trial.
AB  - PURPOSE: To test the effectiveness of static and dynamic orthoses using them as
      an exclusive treatment for proximal interphalangeal (PIP) joint flexion
      contracture compared with other hand therapy conservative treatments described in
      the literature. METHODS: 60 patients who used orthoses were compared with a
      control group that received other hand therapy treatments. Clinical assessments
      were measured before the experiment and 3 months after and included active PIP
      joint extension and function. RESULTS: A significant improvement in the extension
      active range of motion at the PIP joint in the second measurement was found in
      both groups, but it was significantly greater in the experimental group.
      Improvement in function (Disabilities of the Arm, Shoulder, and Hand score)
      between the first and second assessment was similar in the control and
      experimental groups. CONCLUSIONS: Using night progressive static and daily
      dynamic orthoses as an exclusive treatment during the proliferative phase led to
      significant improvements in the PIP joint active extension, but the improvement
      did not correlate with increased function as perceived by the patient. TYPE OF
      STUDY/LEVEL OF EVIDENCE: Therapeutic I.

PMID- 25771482
TI  - How economic crises affect alcohol consumption and alcohol-related health
      problems: a realist systematic review.
AB  - Economic crises are complex events that affect behavioral patterns (including
      alcohol consumption) via opposing mechanisms. With this realist systematic
      review, we aimed to investigate evidence from studies of previous or ongoing
      crises on which mechanisms (How?) play a role among which individuals (Whom?).
      Such evidence would help understand and predict the potential impact of economic
      crises on alcohol consumption. Medical, psychological, social, and economic
      databases were used to search for peer-reviewed qualitative or quantitative
      empirical evidence (published January 1, 1990-May 1, 2014) linking economic
      crises or stressors with alcohol consumption and alcohol-related health problems.
      We included 35 papers, based on defined selection criteria. From these papers, we
      extracted evidence on mechanism(s), determinant, outcome, country-level context,
      and individual context. We found 16 studies that reported evidence completely
      covering two behavioral mechanisms by which economic crises can influence alcohol
      consumption and alcohol-related health problems. The first mechanism suggests
      that psychological distress triggered by unemployment and income reductions can
      increase drinking problems. The second mechanism suggests that due to tighter
      budget constraints, less money is spent on alcoholic beverages. Across many
      countries, the psychological distress mechanism was observed mainly in men. The
      tighter budget constraints mechanism seems to play a role in all population
      subgroups across all countries. For the other three mechanisms (i.e.,
      deterioration in the social situation, fear of losing one's job, and increased
      non-working time), empirical evidence was scarce or absent, or had small to
      moderate coverage. This was also the case for important influential contextual
      factors described in our initial theoretical framework. This realist systematic
      review suggests that among men (but not among women), the net impact of economic
      crises will be an increase in harmful drinking. Such a different net impact
      between men and women could potentially contribute to growing gender-related
      health inequalities during a crisis. 

PMID- 25771481
TI  - The signs of stress: embodiments of biosocial stress among type 2 diabetic women
      in New Delhi, India.
AB  - Biocultural models of health and illness are increasingly used to trace how
      social pathways shape biological outcomes. Yet, data on the interactions between
      social and biological aspects of health are lacking in low- and middle-income
      regions, where two-thirds of all type 2 diabetes cases occur. This study explored
      health, social roles, and biological correlates among a group of 280 type 2
      diabetic and non-diabetic women (n = 184 diabetic) in New Delhi, India, between
      2009 and 2011. Using a biocultural framework, we developed and tested a series of
      hypotheses about the relationships that might exist between diabetes,
      psychological distress, social role fulfillment, and biological markers measuring
      blood sugar control, generalized inflammation, and immune stress. Although blood
      glucose and glycated hemoglobin levels indicated that women's diabetes was
      generally poorly controlled, they lacked the elevated inflammation, immune
      stress, and mental ill health that often accompany uncontrolled blood sugar.
      Qualitative work on explanatory models of diabetes and gendered models of
      appropriate behavior demonstrated that despite living with poorly controlled
      diabetes, women maintain participation in culturally valued roles involving the
      care of others. We suggest that behavioral congruence with these gendered roles
      may buffer diabetic women's mental health and perhaps even their long-term
      physical health, while simultaneously posing challenges for their diabetes self
      care. To our knowledge, this is the first study to explore the experience of type
      2 diabetes in India from an integrated biocultural perspective. 

PMID- 25771483
TI  - Hegemony in the marketplace of biomedical innovation: consumer demand and stem
      cell science.
AB  - The global political economy of stem cell therapies is characterised by an
      established biomedical hegemony of expertise, governance and values in collision
      with an increasingly informed health consumer demand able to define and pursue
      its own interest. How does the hegemony then deal with the challenge from the
      consumer market and what does this tell us about its modus operandi? In
      developing a theoretical framework to answer these questions, the paper begins
      with an analysis of the nature of the hegemony of biomedical innovation in
      general, its close relationship with the research funding market, the current
      political modes of consumer incorporation, and the ideological role performed by
      bioethics as legitimating agency. Secondly, taking the case of stem cell
      innovation, it explores the hegemonic challenge posed by consumer demand working
      through the global practice based market of medical innovation, the response of
      the national and international institutions of science and their reassertion of
      the values of the orthodox model, and the supporting contribution of bioethics.
      Finally, the paper addresses the tensions within the hegemonic model of stem cell
      innovation between the key roles and values of scientist and clinician, the
      exacerbation of these tensions by the increasingly visible demands of health
      consumers, and the emergence of political compromise. 

PMID- 25771484
TI  - Identification of novel inhibitors of Aurora A with a 3-(pyrrolopyridin-2
      yl)indazole scaffold.
AB  - A novel series of 3-(pyrrolopyridin-2-yl)indazole derivatives were synthesized
      and biologically evaluated for their anti-proliferative effects on five human
      cancer cell lines. As a result, all of them exhibited vigorous potency against
      HL60 cell line with IC50 values ranging from singe digital nanomolar to
      micromolar level. Besides, a majority of them displayed modest to good
      antiproliferative activities against the other four cell lines, including KB,
      SMMC-7721, HCT116, and A549. Particularly, compound 2y, as the most distinguished
      one in this series, demonstrated IC50 values of 8.3nM and 1.3nM against HL60 and
      HCT116 cell lines, respectively. Afterwards, for exploring the molecular target,
      compounds2d, 2g and 2y were further selected to evaluate the inhibitory
      activities against a panel of kinases. Finally, they were identified to be
      targeting Aurora A kinase with significant selectivity over other kinases, such
      as CHK1, CDK2, MEK1, GSK3beta, BRAF, IKKbeta and PKC. 

PMID- 25771486
TI  - Endogenous viruses: Connecting recent and ancient viral evolution.
AB  - The rapid rates of viral evolution allow us to reconstruct the recent history of
      viruses in great detail. This feature, however, also results in rapid erosion of
      evolutionary signal within viral molecular data, impeding studies of their deep
      history. Thus, the further back in time, the less accurate the inference becomes.
      Furthermore, reconstructing complex histories of transmission can be challenging,
      especially where extinct viral lineages are concerned. This problem has been
      partially solved by the discovery of viruses embedded in host genomes, known as
      endogenous viral elements (EVEs). Some of these endogenous viruses are derived
      from ancient relatives of extant viruses, allowing us to better examine ancient
      viral host range, geographical distribution and transmission routes. Moreover,
      our knowledge of viral evolutionary timescales and rate dynamics has also been
      greatly improved by their discovery, thereby bridging the gap between recent and
      ancient viral evolution. 

PMID- 25771485
TI  - Strategies to make protein serine/threonine (PP1, calcineurin) and tyrosine
      phosphatases (PTP1B) druggable: achieving specificity by targeting substrate and
      regulatory protein interaction sites.
AB  - The established dogma is that protein serine/threonine (PSPs) and tyrosine (PTPs)
      phosphatases are unattainable drug targets. This is because natural product
      inhibitors of PSP active sites are lethal, while the active sites of PTPs are
      exceptionally conserved and charged, making it nearly impossible to develop PTP
      inhibitors that are selective. However, due to a series of recent structural and
      functional studies, this view of phosphatases is about to undergo a radical
      change. Rather than target active sites, these studies have demonstrated that
      targeting PSP/PTP protein (substrate/regulatory) interaction sites, which are
      distal from the active sites, are highly viable and suitable drugs targets. This
      is especially true for calcineurin (CN), in which the blockbuster
      immunosuppressant drugs FK506 and cyclosporin A were recently demonstrated to
      bind and block one of the key CN substrate interaction sites, the LxVP site.
      Additional studies show that this approach-targeting substrate and/or regulatory
      protein interaction sites-also holds incredible promise for protein phosphatase 1
      (PP1)-related diseases. Finally, domains outside PTP catalytic domains have also
      recently been demonstrated to directly alter PTP activity. Collectively, these
      novel insights offer new, transformative perspectives for the therapeutic
      targeting of PSPs by interfering with the binding of PIPs or substrates and PTPs
      by targeting allosteric sites outside their catalytic domains.

PMID- 25771488
TI  - Species-dependent binding of new synthesized bicalutamide analogues to albumin by
      optical biosensor analysis.
AB  - The binding of some novel bicalutamide analogues to human serum albumin (HSA) and
      rat serum albumin (RSA) was investigated by surface plasmon resonance (SPR) based
      optical biosensor technique. The serum protein binding of the bicalutamide
      analogues was determined and compared to that of the parent compound.
      Furthermore, HSA and RSA were used as target plasma proteins, in order to
      highlight possible differences among species when performing pharmacokinetic
      studies. HSA and RSA were covalently immobilized on carboxymethyl dextran
      matrixes, using an amine coupling procedure. The anchoring method was validated
      by determining the dissociation constant (KD) of a standard analyte to confirm
      that the binding properties of the proteins were maintained. The ranking of the
      bicalutamide analogues for their HSA and RSA bound fractions was used to compare
      the behaviour of the two albumins. Most of the bicalutamide analogues showed
      higher binding levels with respect to the lead compound, (R)-bicalutamide.
      Further, meaningful differences in the binding level to the two serum proteins
      were obtained. The dissociation constants (KD) of the interaction between the
      lead compound, (R)-bicalutamide, and the two proteins were calculated. As a
      result, the KD obtained with HSA was one order of magnitude higher than that
      obtained with RSA. The observed differences in the HSA and RSA bonding of the
      bicalutamide analogues increase the knowledge on the possible low reliability in
      extrapolating the distribution data obtained on animals to humans. This work
      demonstrates that SPR based optical biosensor technique is well suited for the
      medium-high throughput screening of compounds' ligand binding to serum albumins. 

PMID- 25771487
TI  - The 3 facets of regulation of herpes simplex virus gene expression: A critical
      inquiry.
AB  - On entry into the body herpes simplex viruses (HSV) replicate in a series of
      steps that involves derepression of viral DNA activated by VP16, a virion
      protein, and sequential transcription of viral genes in a cascade fashion. HSV
      also enters into neurons in which viral DNA maintained as heterochromatin and
      with few exceptions viral gene expression is silenced. A third face of the
      interaction of HSV with its host cells takes place at the moment when the
      silenced viral genome in neurons is abruptly derepressed. The available data do
      no reveal evidence that HSV encodes different regulatory programs for each facet
      of its interaction with its host cells. Rather the data point to significant gaps
      in our knowledge of the mechanisms by which each facet is initiated and the roles
      of the infected cells at each facet of the interaction of viral gene products
      with the host cell. 

PMID- 25771489
TI  - Non-equilibrium conformational dynamics in the function of molecular chaperones.
AB  - Why do chaperones need ATP hydrolysis to help proteins reach their native,
      functional states? In this review, we highlight the most recent experimental and
      theoretical evidences suggesting that ATP hydrolysis allows molecular chaperones
      to escape the bounds imposed by equilibrium thermodynamics. We argue here that
      energy consumption must be fully taken into account to understand the mechanism
      of these intrinsically non-equilibrium machines and we propose a novel
      perspective in the way the relation between function and ATP hydrolysis is
      viewed. 

PMID- 25771490
TI  - Capsaicin-containing chili improved postprandial hyperglycemia, hyperinsulinemia,
      and fasting lipid disorders in women with gestational diabetes mellitus and
      lowered the incidence of large-for-gestational-age newborns.
AB  - BACKGROUND & AIMS: Gestational diabetes mellitus (GDM) may increase the future
      health risks of women and their offspring. The aim of this study was to determine
      the effect of capsaicin supplementation on blood glucose, lipid metabolism and
      pregnancy outcomes in women with GDM. METHODS: Forty-four pregnant women with GDM
      at 22-33 gestational weeks were randomly assigned to the capsaicin group (5 mg/d
      of capsaicin) or to the placebo group (0 mg/d of capsaicin) for 4 weeks in a
      randomized, double-blind, placebo-controlled trial. The concentrations of fasting
      plasma glucose and serum insulin, 2-h postprandial plasma glucose (2-h PG) and
      serum insulin (2-h INS), and fasting serum lipids, liver and kidney function
      parameters, and calcitonin gene-related peptide (CGRP) were measured at 0 and 4
      weeks. The maternal and neonatal outcomes were also recorded. RESULTS: Forty-two
      women completed the trial. Compared to the placebo group, 2-h PG and 2-h INS
      concentrations and 2-h postprandial HOMA-IR (2-h HOMA-IR) levels, and the fasting
      serum total cholesterol and triglycerides concentrations significantly decreased
      in the capsaicin group after treatment (P < 0.05). Moreover, the fasting serum
      apolipoprotein B and CGRP concentrations significantly increased in the capsaicin
      group (P < 0.05). The changes in the 2-h PG and 2-h INS concentrations and in the
      2-h HOMA-IR were negatively correlated with the change in the serum CGRP
      concentration (P < 0.05). Furthermore, the incidence of large-for-gestational-age
      (LGA) newborns was significantly lower in the capsaicin group than in the placebo
      group (P = 0.022). CONCLUSIONS: Capsaicin-containing chili supplementation
      regularly improved postprandial hyperglycemia and hyperinsulinemia as well as
      fasting lipid metabolic disorders in women with GDM, and it decreased the
      incidence of LGA newborns.

PMID- 25771491
TI  - Physiological responses and scope for growth upon medium-term exposure to the
      combined effects of ocean acidification and temperature in a subtidal scavenger
      Nassarius conoidalis.
AB  - Physiological responses (ingestion rate, absorption rate and efficiency,
      respiration, rate, excretion rate) and scope for growth of a subtidal scavenging
      gastropod Nassarius conoidalis under the combined effects of ocean acidification
      (pCO2 levels: 380, 950, 1250 MUatm) and temperature (15, 30  degrees C) were
      investigated for 31 days. There was a significant reduction in all the
      physiological rates and scope for growth following short-term exposure (1-3 days)
      to elevated pCO2 except absorption efficiency at 15  degrees C and 30  degrees C,
      and respiration rate and excretion rate at 15  degrees C. The percentage change
      in the physiological rates ranged from 0% to 90% at 15  degrees C and from 0% to
      73% at 30  degrees C when pCO2 was increased from 380 MUatm to 1250 MUatm. The
      effect of pCO2 on the physiological rates was enhanced at high temperature for
      ingestion, absorption, respiration and excretion. When the exposure period was
      extended to 31 days, the effect of pCO2 was significant on the ingestion rate
      only. All the physiological rates remained unchanged when temperature increased
      from 24  degrees C to 30  degrees C but the rates at 15  degrees C were
      significantly lower, irrespective of the duration of exposure. Our data suggested
      that a medium-term exposure to ocean acidification has no effect on the
      energetics of N. conoidalis. Nevertheless, the situation may be complicated by a
      longer term of exposure and/or a reduction in salinity in a warming world.

PMID- 25771492
TI  - Spiral rotational flap for the creation of a new umbilicus in bladder exstrophy.
AB  - OBJECTIVE: A range of surgical techniques have been described to create a new
      umbilicus in children with bladder exstrophy. We present a detailed video
      demonstrating our technique for the creation of a new umbilicus. METHOD: The
      position of the planned umbilicus and flap were marked on the abdomen. Incisions
      were made using monopolar diathermy. The flap was raised and excess fat thinned.
      Subcutaneous tissues were apposed, and the flap rotated and sutured in spiral
      fashion with interrupted 6/0 monocryl forming a cone which was subsequently
      inverted. RESULTS: Between May 1999 and August 2014, we used this technique for
      the creation of a new umbilicus in 47 bladder exstrophy patients (31 boys and 16
      girls). No complications occurred. All were followed up as part of our bladder
      exstrophy programme. CONCLUSION: The technique allows reproducible excellent
      cosmetic results. Aesthetic results are durable and it should be considered as an
      alternative to existing reported techniques.

PMID- 25771493
TI  - Fluoxetine prevents respiratory arrest without enhancing ventilation in DBA/1
      mice.
AB  - Sudden unexpected death in epilepsy (SUDEP) is a fatal epileptic event. DBA/1
      mice are a relevant animal model for the study of SUDEP, as these mice exhibit
      seizure-induced respiratory arrest (S-IRA) leading to death, which has been
      observed in patients with witnessed SUDEP. Fluoxetine, a selective serotonin (5
      hydroxytryptamine or 5-HT) reuptake inhibitor (SSRI), reduces S-IRA in DBA/1
      mice. Given that DBA/1 mice with S-IRA can be resuscitated using a ventilator, we
      hypothesized that breathing stimulants can prevent S-IRA and that fluoxetine
      prevents S-IRA by enhancing ventilation in these mice. Spontaneous respiratory
      function in anesthetized or awake DBA/1 mice was examined using noninvasive
      plethysmography before and after administering fluoxetine or breathing
      stimulants, doxapram, and 5,6,7,8-tetrahydropyrido[4,3-d]pyrimidine (PK-THPP).
      The effects of these drugs on S-IRA in DBA/1 mice were tested. As reported
      previously, systemic administration of fluoxetine reduced S-IRA in awake DBA/1
      mice, but fluoxetine in anesthetized and awake DBA/1 mice did not increase basal
      ventilation or the ventilatory response to 7% CO2. Both doxapram and PK-THPP
      increased ventilation in room air and in air+7% CO2 in anesthetized DBA/1 mice.
      However, neither of the breathing stimulants reduced the incidence of S-IRA. Our
      studies confirm that fluoxetine reduces S-IRA in DBA/1 mice without enhancing
      basal ventilation in the absence of seizures. Although breathing stimulants
      increased ventilation in the absence of seizures, they were ineffective in
      reducing S-IRA, indicating that drug-induced increases in ventilation are
      insufficient to compensate for S-IRA in DBA/1 mice. 

PMID- 25771494
TI  - The association between nonsuicidal self-injury and the emotional disorders: A
      meta-analytic review.
AB  - Existing research supports a relationship between nonsuicidal self-injury (NSSI)
      and the emotional disorders (i.e., anxiety, mood, and related disorders). The aim
      of this investigation was to conduct a meta-analysis of the associations between
      NSSI and the emotional disorders, and evaluate the quality of evidence supporting
      this relationship. A literature search was conducted from database inception
      through June 2014, and two reviewers independently determined the eligibility and
      quality of studies. A total of 56 articles providing data on engagement in NSSI
      among individuals with and without emotional disorders met eligibility criteria.
      Compared to those without an emotional disorder, individuals with an emotional
      disorder were more likely to report engagement in NSSI (OR=1.75, 95% CI: 1.49,
      2.06). This increase of risk of NSSI was shown for each disorder subgroup, with
      the exceptions of bipolar disorder and social anxiety disorder. The largest
      associations were observed for panic and post-traumatic stress disorder; however,
      the risk of NSSI did not differ significantly across disorders. The quality of
      evidence was variable due to inconsistent methodological factors (e.g.,
      adjustment for confounding variables, NSSI assessment). Overall, these findings
      provide evidence for a relationship between NSSI and the emotional disorders, and
      support conceptualizations of NSSI as transdiagnostic.

PMID- 25771495
TI  - Sentinel node mapping with indocyanine green and endoscopic near-infrared
      fluorescence imaging in endometrial cancer. A pilot study and review of the
      literature.
AB  - OBJECTIVES: Indocyanine green (ICG) with near-infrared (NIR) fluorescence imaging
      is a new tracer modality used for lymphatic mapping. We report our initial
      experience with ICG for SLN mapping in cervical and endometrial cancer using a
      new endoscopic fluorescence imaging system. METHODS: We reviewed all patients who
      underwent primary surgery for early-stage endometrial and cervical carcinoma with
      SLN mapping using fluorescence imaging followed by pelvic lymphadenectomy from
      February to July 2014. Intracervical injection of ICG at 3 and 9 o'clock was
      performed in all cases. SLNs were ultrastaged on final pathology. Sensitivity and
      specificity values were calculated. RESULTS: A total of 50 patients were included
      in the study (42 endometrial and 8 cervical cancers). The median age was 62 (24
      88) and median BMI 29 (19-56). The median SLN count was 3.1 (0-7) and median
      lymph node count was 15 (2-37). The overall and bilateral detection rate was 96%
      (48/50) and 88% (44/50). Positive SLNs were identified in 22% of patients
      (11/50), including 8 isolated tumor cells (ITC), 2 micrometastasis and 1
      macrometastasis. There was one side-specific false negative case. Sensitivity,
      specificity and NPV were 93.3%, 100% and 98.7% respectively per side. Paraaortic
      node dissection was performed in 22% of cases. Two had paraaortic node metastasis
      both in patients with positive pelvic SLN. There were no allergic reactions to
      the ICG. CONCLUSIONS: Based on our pilot experience, NIR fluorescence imaging
      with ICG is an excellent and safe tracer modality for SLN mapping with a very
      high overall (96%) and bilateral (88%) detection rate.

PMID- 25771497
TI  - Conserved amino acids within the N-terminus of the West Nile virus NS4A protein
      contribute to virus replication, protein stability and membrane proliferation.
AB  - The West Nile virus strain Kunjin virus (WNVKUN) NS4A protein is a
      multifunctional protein involved in many aspects of the virus life-cycle and is a
      major component of the WNVKUN replication complex (RC). Previously we identified
      a conserved region in the C-terminus of NS4A regulating proteolytic processing
      and RC assembly, and now investigate key conserved residues in the N-terminus of
      NS4A and their contribution to WNVKUN replication. Mutation of P13 completely
      ablated replication, whereas, mutation of P48 and D49, near the first
      transmembrane helix, and G66 within the helix, showed variable defects in
      replication, virion secretion and membrane proliferation. Intriguingly, the P48
      and G66 NS4A mutants resulted in specific proteasome depletion of NS4A that could
      in part be rescued with a proteasome inhibitor. Our results suggest that the N
      terminus of NS4A contributes to correct folding and stability, essential for
      facilitating the essential roles of NS4A during replication. 

PMID- 25771496
TI  - The HPV16 and MusPV1 papillomaviruses initially interact with distinct host
      components on the basement membrane.
AB  - To understand and compare the mechanisms of murine and human PV infection, we
      examined pseudovirion binding and infection of the newly described MusPV1 using
      the murine cervicovaginal challenge model. These analyses revealed primary tissue
      interactions distinct from those previously described for HPV16. Unlike HPV16,
      MusPV1 bound basement membrane (BM) in an HSPG-independent manner. Nevertheless,
      subsequent HSPG interactions were critical. L2 antibodies or low doses of VLP
      antibodies, sufficient to prevent infection, did not lead to disassociation of
      the MusPV1 pseudovirions from the BM, in contrast to previous findings with
      HPV16. Similarly, furin inhibition did not lead to loss of MusPV1 from the BM.
      Therefore, phylogenetically distant PV types differ in their initial interactions
      with host attachment factors, but initiate their lifecycle on the acellular BM.
      Despite these differences, these distantly related PV types displayed similar
      intracellular trafficking patterns and susceptibilities to biochemical inhibition
      of infection. 

PMID- 25771498
TI  - Comparison of traditional intranasal and aerosol inhalation inoculation of mice
      with influenza A viruses.
AB  - Intranasal instillation of virus in a liquid suspension (IN) is the most
      frequently employed method to inoculate small mammalian models with influenza
      virus, but does not reflect a natural route of exposure. In contrast, inoculation
      via aerosol inhalation (AR) more closely resembles human exposure to influenza
      virus. Studies in mice have yielded conflicting results regarding virulence
      induced by virus inoculated by these routes, and have not controlled for
      potential strain-specific differences, or examined contemporary influenza viruses
      and avian viruses with pandemic potential. We used a whole-body AR inoculation
      method to compare infectivity and disease progression of a highly pathogenic
      H5N1, a low pathogenic H7N9, and a 2009 H1N1 virus with traditional IN
      inoculation in the mouse model. Generally comparable levels of morbidity and
      mortality were observed with all viruses examined using either inoculation route,
      indicating that both IN and AR delivery are appropriate for murine studies
      investigating influenza virus pathogenicity. 

PMID- 25771499
TI  - Survival after Public Access Defibrillation in Stockholm, Sweden--A striking
      success.
AB  - BACKGROUND: In Stockholm, a first responder system and a Public Access
      Defibrillation (PAD) program has been implemented. Additionally, the number of
      "unregulated" public Automated External Defibrillators (AEDs) sold "over-the
      counter" has increased. The aim of this study was to evaluate the impact on
      survival from different defibrillation strategies in cases of out-of-hospital
      cardiac arrest (OHCA) available for PAD. METHODS AND RESULTS:  DESIGN:
      Retrospective study of all OHCAs in Stockholm, 2006-2012. Witnessed OHCAs
      occurring outside home with cardiac origin and ventricular fibrillation were
      considered subjects for PAD. The sites within the PAD program increased from 60
      to 135 while the number of unregulated AEDs outside the PAD program increased
      from 178 to 5016. Of 6532 OHCAs, 7% (n = 474) were defined as subjects for PAD.
      Of these, 69% (n = 326) were defibrillated by the EMS, 11% (n = 53) by first
      responders and 16% (n =7 4) by public AEDs. Survival to one month was 31% (n =
      101) for cases defibrillated by the EMS, 42% (n = 22) when defibrillated by first
      responders and 70% (n = 52) when defibrillated by a public AED. The AEDs within
      the PAD program constituted 2.6% of all public AEDs and were used in 28% (n = 21)
      of cases when a public AED was used. CONCLUSIONS: In OHCAs available for PAD, 70%
      of patients survived if a public AED was used. Both the structured AED program as
      well as the spread of unregulated AEDs was associated with very high survival
      rates, but the structured approach was more efficient in relation to the number
      of AEDs used.

PMID- 25771500
TI  - Frequency and number of resuscitation related rib and sternum fractures are
      higher than generally considered.
AB  - AIM OF THE STUDY: This study aimed to establish the incidence, number and
      location of CPR-related skeletal chest injuries (SCI) and to investigate the
      influence of age, gender, changes in resuscitation guidelines and technique of
      resuscitation. METHODS: We analysed SCI in 2148 patients who had undergone
      resuscitation for non-traumatic cardiac arrest, as shown by autopsies performed
      at the Institute of Forensic Medicine in Ljubljana in the period 2004-2013.
      RESULTS: External cardiac massage caused SCI in 86% of males and in 91% of
      females; sternum fractures occurred in 59% of males and 79% of females, rib
      fractures in 77% of males and 85% of females and sternocostal separations in 33%
      of males and 12% of females. The average number of all SCI per person was thus
      almost the same in males and females: 10.95 vs. 10.96. The percentage of patients
      injured and the number of SCI increased with age. Changes in resuscitation
      guidelines were also identified as a factor contributing to the incidence and
      number of SCI. No adverse effect of the use of LUCAS was found. CONCLUSION: It is
      generally considered that at least 1/3 of resuscitated patients sustain rib
      fractures and at least 1/5 sustains sternum fractures. However, our study showed
      that these injuries are much more frequent and that increased compression rate
      and depth cause more SCI. Since in the period 2011-2013 accompanying severe
      injuries occurred in only 1.85% of cases, the resuscitation technique has not yet
      jeopardised patient's safety, but further close monitoring is needed.

PMID- 25771501
TI  - Impact of bystander-performed ventilation on functional outcomes after cardiac
      arrest and factors associated with ventilation-only cardiopulmonary
      resuscitation: A large observational study.
AB  - AIM: To determine the effectiveness of ventilations in bystander cardiopulmonary
      resuscitation (BCPR) and to identify the factors associated with ventilation-only
      BCPR. METHODS: From out-of-hospital cardiac arrest (OHCA) data prospectively
      collected from 2005 to 2011 in Japan, we extracted data for 210,134 bystander
      witnessed OHCAs with complete datasets but no prehospital involvement of
      physician [no BCPR, 115,733; ventilation-only, 2093; compression-only, 61,075;
      and conventional (compressions+ventilations) BCPR, 31,233] and determined the
      factors associated with 1-month neurologically favourable survival using simple
      and multivariable logistic regression analyses. In 91,885 patients with known
      BCPR durations, we determined the factors associated with ventilation-only BCPR.
      RESULTS: The rate of survival in the no BCPR, ventilation-only, compression-only
      and conventional group was 2.8%, 3.9%, 4.5% and 5.0%, respectively. After
      adjustment for other factors associated with outcomes, the survival rate in the
      ventilation-only group was higher than that in the no BCPR group (adjusted OR;
      95% CI, 1.29; 1.01-1.63), but lower than that in the compression-only (0.76; 0.59
      0.96) or conventional groups (0.70; 0.55-0.89). Conventional CPR had the highest
      OR for survival in almost all OHCA subgroups. The adjusted OR (95% CI) for
      survival after dividing BCPR into ventilation and compression components was 1.19
      (1.11-1.27) and 1.60 (1.51-1.69), respectively. Older guidelines, female sex,
      younger patient age, bystander-initiated CPR without instruction, early BCPR and
      short BCPR duration were associated with ventilation-only BCPR. CONCLUSIONS:
      Ventilation is a significant component of BCPR, but alone is less effective than
      compression in improving neurologically favourable survival after OHCAs.

PMID- 25771502
TI  - Expansion of the Chlamydia trachomatis inclusion does not require bacterial
      replication.
AB  - Chlamydia trachomatis replication takes place inside of a host cell, exclusively
      within a vacuole known as the inclusion. During an infection, the inclusion
      expands to accommodate the increasing numbers of C. trachomatis. However, whether
      inclusion expansion requires bacterial replication and/or de novo protein
      synthesis has not been previously investigated in detail. Therefore, using a
      chemical biology approach, we herein investigated C. trachomatis inclusion
      expansion under varying conditions in vitro. Under normal cell culture
      conditions, inclusion expansion correlated with C. trachomatis replication. When
      bacterial replication was inhibited using KSK120, an inhibitor that targets C.
      trachomatis glucose metabolism, inclusions expanded even in the absence of
      bacterial replication. In contrast, when bacterial protein synthesis was
      inhibited using chloramphenicol, expansion of inclusions was blocked. Together,
      these data suggest that de novo protein synthesis is necessary, whereas bacterial
      replication is dispensable for C. trachomatis inclusion expansion. 

PMID- 25771503
TI  - Evolution of glycated haemoglobin in adults on growth hormone replacement
      therapy.
AB  - OBJECTIVES: To evaluate the effects of GH replacement therapy (GHR) for 3 years
      on glycated haemoglobin (HbA1c) and on the presence of dysglycaemia at any time
      during follow-up in Spanish adult patients with growth hormone deficiency (GHD).
      STUDY DESIGN: A retrospective study of 41 patients with GHD was conducted using
      baseline and long-term data. Changes in HbA1c values during the first 3 years of
      GHR were studied in both the overall population and patients with or without
      dysglycaemia during follow-up. Dysglycaemia was defined as FPG >= 100 mg/dl
      and/or HbA1c >= 5.7%. RESULTS: Mean HbA1c value (5.4 +/- 0.4% at baseline)
      increased during the first and second years of GHR (HbA1c 5.5 +/- 0.4%, p=0.05,
      and 5.5 +/- 0.4%, p=0.006 respectively). This increase was not maintained during
      the third year (HbA1c 5.4 +/- 0.3%, p=0.107) of GHR. Twenty-eight patients
      (68.2%) had dysglycaemia during follow-up, 9 of them since baseline. In the 19
      patients without baseline dysglycaemia, HbA1c increased during the first year and
      remained stable in the next 2 years (mean HbA1c 5.2 +/- 0.4% at baseline; 5.5 +/-
      0.4% at 1 year, p<0.050; 5.4 +/- 0.4% at 2 years, p=0.004, and 5.4 +/- 0.4% at 3
      years, p=0.016). In the 9 patients with baseline dysglycaemia, HbA1c did not
      significantly change during the 3 years of GHR therapy. CONCLUSIONS: HbA1c values
      increased during the first 2 years of GHR therapy. In patients with no
      dysglycaemia before treatment, HbA1c steadily increased over the 3 years.
      However, it did not change in patients with baseline dysglycaemia.

PMID- 25771504
TI  - Inflammasome control of viral infection.
AB  - The inflammasome is a caspase-1 containing complex that activates the
      proinflammatory cytokines IL-1beta and IL-18 and results in the proinflammatory
      cell death known as pyroptosis. Numerous recent publications have highlighted the
      importance of inflammasome activation in the control of virus infection.
      Inflammasome activation during viral infection is dependent on a variety of
      upstream receptors including the NOD-like receptor, RIG-I-like receptor and AIM2
      like receptor families. Various receptors also function in inflammasome
      activation in different cellular compartments, including the cytoplasm and the
      nucleus. The effectiveness of inflammasomes at suppressing virus replication is
      highlighted by the prevalence and diversity of virus encoded inflammasome
      inhibitors. Also, the host has a myriad of regulatory mechanisms in place to
      prevent unwanted inflammasome activation and overt inflammation. Finally, recent
      reports begin to suggest that inflammasome activation and inflammasome modulation
      may have important clinical applications. Herein, we highlight recent advances
      and discuss potential future directions toward understanding the role of
      inflammasomes during virus infection. 

PMID- 25771505
TI  - The unique regulation and functions of type III interferons in antiviral
      immunity.
AB  - Type I interferons (IFNs) were long considered to be the sole IFN species
      produced by virus-infected cells until the discovery of type III IFNs
      (IFNlambdas), decades later. Like type I IFNs, type III IFNs are induced by and
      protect against viral infections, leading to the initial conclusion that the two
      IFN species are identical in regulation and biological functions. However, the
      two systems differ in the tissue expression of their receptor, resulting in
      different roles in vivo. The unique nature of IFNlambdas has been further
      demonstrated by recent studies revealing differences in the regulation of type I
      and III IFN expression, and how these proteins elicit specific cellular
      responses. This review focuses on the distinctive features of type III IFNs in
      antiviral innate immunity. 

PMID- 25771507
TI  - Pollination biology in the dioecious orchid Catasetum uncatum: How does floral
      scent influence the behaviour of pollinators?
AB  - Catasetum is a neotropical orchid genus that comprises about 160 dioecious
      species with a remarkable sexual dimorphism in floral morphology. Flowers of
      Catasetum produce perfumes as rewards, which are collected only by male
      euglossine bees. Currently, floral scents are known to be involved in the
      selective attraction of specific euglossine species. However, sexual dimorphism
      in floral scent and its eventual role in the pollination of Catasetum species
      have never been investigated. Here, we have investigated the pollination of
      Catasetum uncatum and asked: (1) Is floral scent a sexual dimorphic trait? (2)
      Does pollinarium removal/deposition affect scent emission? (3) Does sexual
      dimorphism in floral scent and changed scent emission have implications with
      regard to the behaviour of the pollinators? The frequency and behaviour of floral
      visitors were observed in non-manipulated flowers (both flower sexes) and in
      manipulated flowers (pistillate only) in which pollinaria were deposited. Scents
      of staminate and pistillate flowers (both manipulated and non-manipulated) were
      collected by using dynamic headspace methods and analysed chemically.
      Electrophysiological analyses were performed to detect compounds triggering
      antennal depolarisation in the euglossine species. C. uncatum is pollinated
      mainly by males of Euglossa nanomelanotricha. Pollinators were more frequent in
      pistillate than in staminate inflorescences. Bees approaching staminate flowers
      frequently flew away without visiting them, a behavioural pattern not observed in
      pistillate flowers. In the chemical analyses, we recorded 99 compounds, 31 of
      which triggered antennal depolarisation in pollinators. Multivariate analyses
      with the electrophysiological-active compounds did not detect differences between
      the scent composition of staminate and pistillate flowers. Pollinarium removal or
      deposition resulted in diminished scent emission within 24h in staminate and
      pistillate flowers, respectively. Surprisingly, bees discriminated pollinated
      from non-pollinated pistillate flowers as early as 2h after pollination. The
      rapid loss in the attractiveness of flowers following pollinarium
      removal/deposition can be interpreted as a strategy to direct pollinators to non
      pollinated flowers. We have found no evidence that euglossine males discriminate
      staminate from pistillate flowers by means of floral scent. Instead, we speculate
      that bees use visual cues, such as sex dimorphic traits, to discriminate flowers
      of different sexes. Together, our results provide interesting insights into the
      evolution of floral signals in gender-dimorphic species and into its significance
      in plant reproductive biology. 

PMID- 25771506
TI  - Chronic Stress Induces Brain Region-Specific Alterations of Molecular Rhythms
      that Correlate with Depression-like Behavior in Mice.
AB  - BACKGROUND: Emerging evidence implicates circadian abnormalities as a component
      of the pathophysiology of major depressive disorder (MDD). The suprachiasmatic
      nucleus (SCN) of the hypothalamus coordinates rhythms throughout the brain and
      body. On a cellular level, rhythms are generated by transcriptional,
      translational, and posttranslational feedback loops of core circadian genes and
      proteins. In patients with MDD, recent evidence suggests reduced amplitude of
      molecular rhythms in extra-SCN brain regions. We investigated whether
      unpredictable chronic mild stress (UCMS), an animal model that induces a
      depression-like physiological and behavioral phenotype, induces circadian
      disruptions similar to those seen with MDD. METHODS: Activity and temperature
      rhythms were recorded in C57BL/6J mice before, during, and after exposure to
      UCMS, and brain tissue explants were collected from Period2 luciferase mice
      following UCMS to assess cellular rhythmicity. RESULTS: UCMS significantly
      decreased circadian amplitude of activity and body temperature in mice, similar
      to findings in MDD patients, and these changes directly correlated with
      depression-related behavior. While amplitude of molecular rhythms in the SCN was
      decreased following UCMS, surprisingly, rhythms in the nucleus accumbens (NAc)
      were amplified with no changes seen in the prefrontal cortex or amygdala. These
      molecular rhythm changes in the SCN and the NAc also directly correlated with
      mood-related behavior. CONCLUSIONS: These studies found that circadian rhythm
      abnormalities directly correlate with depression-related behavior following UCMS
      and suggest a desynchronization of rhythms in the brain with an independent
      enhancement of rhythms in the NAc.

PMID- 25771508
TI  - A metabolomic assessment of NAC154 transcription factor overexpression in field
      grown poplar stem wood.
AB  - Several xylem-associated regulatory genes have been identified that control
      processes associated with wood formation in poplar. Prominent among these are the
      NAC domain transcription factors (NACs). Here, the putative involvement of
      Populus NAC154, a co-ortholog of the Arabidopsis gene SND2, was evaluated as a
      regulator of "secondary" biosynthetic processes in stem internode tissues by
      interrogating aqueous methanolic extracts from control and transgenic trees.
      Comprehensive untargeted metabolite profiling was accomplished with a liquid
      chromatography-mass spectrometry platform that utilized two different
      chromatographic supports (HILIC and reversed phase) and both positive and
      negative ionization modes. Evaluation of current and previous year tissues
      provided datasets for assessing the effects of NAC154 overexpression in wood
      maturation processes. Phenolic glycoside levels as well as those of oligolignols,
      sucrose and arginine were modulated with phenotypic and chemotypic traits
      exhibiting similar trends. Specifically, increased levels of arginine in the
      NAC154 overexpressing tissues supports a role for the transcription factor in
      senescence/dormancy-associated processes. 

PMID- 25771509
TI  - Cerebrospinal fluid cytokine levels in type 1 narcolepsy patients very close to
      onset.
AB  - Type 1 narcolepsy is caused by a loss of hypocretin (orexin) signaling in the
      brain. Genetic data suggests the disorder is caused by an autoimmune attack on
      hypocretin producing neurons in hypothalamus. This hypothesis has however not yet
      been confirmed by consistent findings of autoreactive antibodies or T-cells in
      patient samples. One explanation for these negative results may be that the
      autoimmune process is no longer active when patients present to the clinic. With
      increasing awareness in recent years, more and more patients have been diagnosed
      closer and closer to disease onset. In this study, we tested whether an active
      immune process in the brain could be detected in these patients, as reflected by
      increased cytokine levels in the cerebrospinal fluid (CSF). Using multiplex
      analysis, we measured the levels of 51 cytokines and chemokines in the CSF of 40
      type 1 narcolepsy patients having varying disease duration. For comparison, we
      used samples from 9 healthy controls and 9 patients with other central
      hypersomnia. Cytokine levels did not differ significantly between controls and
      patients, even in 5 patients with disease onset less than a month prior to CSF
      sampling. 

PMID- 25771511
TI  - Detection of Toxoplasma gondii in free-range, organic pigs in Italy using
      serological and molecular methods.
AB  - Twenty-one free ranging pigs from three organically managed farms in northern
      Italy were examined for Toxoplasma gondii infection status by meat juice
      serology. DNA was extracted from all 21 animals and analysed for T. gondii by
      multilocus nested PCR-RFLP. Results showed a 95.2% prevalence in serology, while
      PCR was positive in 57.1% of infected pigs. Genotyping of amplified loci for Type
      I, Type II and Type I/II patterns, suggests the presence of more than one clonal
      genotype in circulation in these animals. Results of the present study highlight
      the high exposure to T. gondii in organic pig farms in Italy, indicating a
      potential risk for meat consumption. 

PMID- 25771510
TI  - Toll-like receptor 4 and comorbid pain in Interstitial Cystitis/Bladder Pain
      Syndrome: a multidisciplinary approach to the study of chronic pelvic pain
      research network study.
AB  - BACKGROUND: Interstitial Cystitis/Bladder Pain Syndrome (IC/BPS) is a condition
      characterized by pelvic pain and urinary symptoms. Some IC/BPS patients have pain
      confined to the pelvic region, while others suffer widespread pain. Inflammatory
      processes have previously been linked to pelvic pain in IC/BPS, but their
      association with widespread pain in IC/BPS has not been characterized. METHODS:
      Sixty-six women meeting criteria for IC/BPS completed self-report measures of
      pain as part of the Multidisciplinary Approach to the Study of Chronic Pelvic
      Pain (MAPP), collected 3days of saliva for cortisol assays, and provided blood
      samples. Peripheral blood mononuclear cells (PBMCs) were stimulated with Toll
      like Receptor (TLR) 2 and 4 agonists and cytokines were measured in supernatant;
      IL-6 was also measured in plasma. Associations between inflammatory variables and
      the likelihood of endorsing extra-pelvic pain, or the presence of a comorbid
      syndrome, were tested by logistic regression and General Linear Models,
      respectively. A subset of patients (n=32) completed Quantitative Sensory Testing.
      RESULTS: A one standard deviation increase in TLR-4 inflammatory response was
      associated with a 1.59 greater likelihood of endorsing extra-pelvic pain
      (p=.019). Participants with comorbid syndromes also had higher inflammatory
      responses to TLR-4 stimulation in PBMCs (p=.016). Lower pressure pain thresholds
      were marginally associated with higher TLR-4 inflammatory responses (p=.062), and
      significantly associated with higher IL-6 in plasma (p=.031). CONCLUSIONS: TLR-4
      inflammatory responses in PBMCs are a marker of widespread pain in IC/BPS, and
      should be explored in other conditions characterized by medically unexplained
      pain.

PMID- 25771512
TI  - Determination of which virus to use as a process control when testing for the
      presence of hepatitis A virus and norovirus in food and water.
AB  - Noroviruses (genogroup I (NoV GI) and genogroup II (NoV GII)) and the hepatitis A
      virus (HAV) are frequently involved in foodborne infections worldwide. They are
      mainly transmitted via the fecal-oral route, direct person-to-person contact or
      consumption of contaminated water and foods. In food virology, detection methods
      are currently based on identifying viral genomes using real-time reverse
      transcriptase PCR (RT-qPCR). One of the general requirements for detecting these
      viruses in food involves the use of a process control virus to monitor the
      quality of the entire viral extraction procedure as described in the ISO/TS 15216
      1 and 15216-2 standards published in 2013. The selected process control virus
      should have similar morphological and physicochemical properties as the screened
      pathogenic virus and thus have the potential to provide comparable extraction
      efficiency. The aim of this study was to determine which virus should be used for
      process control, murine norovirus (MNV-1) or Mengovirus, when testing for the
      presence of HAV, NoV GI and NoV GII in bottled water, lettuce and semi-dried
      tomatoes. Food samples were spiked with HAV, NoV GI or NoV GII alone or in the
      presence of MNV-1 or Mengovirus. Recovery rates of each pathogenic virus were
      compared to those of both process control viruses using a multiple comparison
      procedure. Neither process control virus influenced the recovery of pathogenic
      virus regardless of the type of food matrix. MNV-1 was the most appropriate virus
      for validating the detection of HAV and NoV GII in all three food matrices as
      well as NoV GI in lettuce. Mengovirus proved to be the most appropriate control
      for NoV GI detection in bottled water and semi-dried tomatoes. The process
      control virus is essential for validating viral detection in food and the choice
      of virus depends on food type and the screened pathogenic virus. 

PMID- 25771513
TI  - [Modern methods of prehospital bleeding management based on the experience and
      standards of tactical medicine].
AB  - Isolated limb hemorrhage represents 60% of avoidable deaths and remains the
      leading cause of death in combat zone. Ideal tourniquet must be light, durable
      and cheap. They should completely stop the flow of arterial blood in the limb,
      and their attachment should be quick and easy. Tourniquets applied in correct
      location save lives by stopping the bleeding. Their use in civil environment
      appear to be particularly relevant in the mass casualties events. Modern bandages
      used by the military, were designed mostly in the form of an elastic bandage,
      which attachment has to be easy and quick. Sequential wrapping of elastic
      dressing around the wound produces compressive force which aim is to stem the
      bleeding by pressing vessel from the outside. Dressings are made of materials
      which adhere well to the wound, causing the seal and leave no fragments in the
      injured tissue. The combination of all components enables fast and effective
      application of the dressing in the most demanding conditions. 

PMID- 25771514
TI  - [Cardiovascular risk and inflammatory markers in patients with hypertension].
AB  - Arterial hypertension (AH) is one of the main risk factors of negative
      cardiovascular (CVR) events and the complex evaluation of CVR is necessary for
      the successful treatment of patients with AH. Simultaneously CVR increases when
      the inflammatory markers levels are elevated. AIM: The aim of study was to
      evaluate the frequency of CVR factors presence and their relation to the
      inflammatory markers in patients with AH. MATERIALS AND METHODS: The study was
      conducted in group of 144 patients (99 men, mean age 45.2 years) with AH and no
      other diagnosed cardiovascular diseases. The clinical assessment included: i.e.
      fasting glucose (FG), total cholesterol (T-C), low density lipoprotein
      cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C), triglycerides
      (TG) and inflammatory markers: fibrinogen, high-sensitive C-reactive protein
      (hsCRP) and leukocytes count (WBC). CVR was assessed based on the presence of the
      risk factors included in the ESC guidelines. RESULTS: Dylipidemia was observed in
      over 90% of patients in the study group (most often as the elevated level of T-C
      and LDL-C), abdominal obesity in 54.9%, more than 3 CVR factors in over 70% and
      increased levels of at least one of inflammatory markers in 40.3% of patients
      (most often hs-CRP - 35.4%). The statistically significant correlations between
      anthropometric parameters (BMI, waist cirfumference), laboratory parameters (HDL
      C, TG) and inflammatory markers were observed, the strongest for BMI versus hs
      CRP (r = 0.42, p < 0.000001). In the logic regression analysis the factors
      increasing the probability of the elevated inflammatory activity turned out to
      be: abdominal obesity - OR 3.05 (95% CI: 1.49 - 12.22; p = 0.002); BMI >= 30
      kg/m2 - OR 3.18 (95% CI: 1.57 - 6.44; p = 0.0012) and the presence of more than 3
      risk factors - OR 2.57 (95% CI: 1.13 - 5.83; p = 0.023). CONCLUSIONS: The
      increased level of inflammatory markers is related to the complex metabolic
      disturbances and the assessment of the activation of inflammatory process
      (especially hsCRP) can be useful in the complex CVR evaluation and profound
      defining of therapeutical goals.

PMID- 25771515
TI  - Evaluation of the effectiveness of methods of endoscopic treatment of bleeding
      from the duodenal mucosa.
AB  - Bleeding from the upper gastrointestinal tract, despite the prevalence of
      endoscopic examinations and endoscopic methods of bleeding control, remains a
      significant problem. Available data indicate nondecreasing mortality of patients
      with active bleeding from the upper gastrointestinal tract although it is
      commonly known that such patients require fast endoscopic diagnosis and urgent
      treatment. Currently, the choice of method of endoscopic treatment of bleeding
      depends mostly on its availability and the decision of the physician performing
      the procedure. AIM: The aim of the study was to evaluate the efficacy of
      different techniques of endoscopic hemostasis from the duodenum, mainly the
      comparison of monotherapy with the use of at least two techniques of endoscopic
      treatment of bleeding used simultaneously. MATERIALS AND METHODS: This paper
      presents a retrospective analysis of medical records of 78 patients (27 women, 51
      men; 33 of them were over 65 years), hospitalized in the Department of
      Nephrology, Hypertension and Family Medicine between 2009 and 2012. In all these
      patients, active bleeding from the duodenum was observed during endoscopy
      performed because of clinical signs of gastrointestinal bleeding, and the
      following methods of blood flow stemming were applied: injection with a solution
      of adrenaline alone or in combination with placement of clips. RESULTS: The use
      of haemostatic clips alone or in a combination with injections of adrenaline
      around the bleeding site was demonstrated to be the most effective method of
      endoscopic control of bleeding from the duodenum. Injections of epinephrine
      around the bleeding site as monotherapy turned out to be the least effective
      method. CONCLUSIONS: The most effective method of endoscopic control of bleeding
      from duodenal ulcers is the use of hemostatic clips alone or preceded by
      adrenaline injections, while the use of injections of adrenaline around the
      bleeding vessel was the least effective method.

PMID- 25771516
TI  - [The degree of asthma severity in children and the level of maternal anxiety and
      depression].
AB  - Care for sick children most often falls to mothers, which may affect their mental
      state, causing the states of depression and anxiety. AIM: The aim of this study
      was to determine the relationship between the severity of asthma in children and
      the level of anxiety and depression in mothers, taking into account the
      importance of the material status of the family, the educational level of the
      mothers, the presence of critical events, as well as the coexistence of allergic
      diseases in other family members. MATERIALS AND METHODS: The study included 60
      mothers of children with bronchial asthma. Age of mothers in the investigated
      families was on average 37.28 +/- 6.24 years, and most had a high school
      education (55.0%) or higher (28.3%). 16.7% of mothers and 8.3% fathers suffered
      from asthma. 13.3% of mothers of children with asthma were brought child alone.
      To assess the level of anxiety the inventory for measuring state and trait
      anxiety (STAI - State Trait Anxiety Inventory) developed by Spielberger,
      Gorsuch'a and Lushene'a was applied. To determine the changes in depressive the
      Beck Depression Inventory (BDI - Beck Depression Inventory questionnaire) was
      used. The Student's t test was included for two independent populations and a
      comparison of the results obtained in the questionnaire for diagnosing the level
      of anxiety and depression. For other parameters the correlation coefficient r
      Pearson rank and Kendall's tau were performed. RESULTS: Mothers of children with
      moderate asthma compared to mothers of children with mild asthma had higher
      levels of anxiety (both state and properties), and also a slightly higher level
      of depression. Maternal age was connected positively and moderately strongly with
      the number held by children (r = 0.380; p = 0.003) and age of a child with asthma
      (r = 0.613, p = 0.0005). The duration of the child's disease was associated
      positively and moderately strongly with the level of state anxiety mother (X-1)
      (r = 0.345; p = 0.007) and a bit less and also positively with the levels of
      depression (r = 0.227; p = 0.081). Maternal age (r = -0.428; p = 0.018) and the
      number of children held by them (r = -0.365; p = 0.047) were correlated
      moderately strongly and negatively with their level of state anxiety (X-1). Very
      strong and positive relationship links the level of trait anxiety (X-2) mothers
      with their levels of depression (r = 0.729; p = 0.0005). CONCLUSIONS: The study
      revealed that there is a relationship between the severity of asthma in children
      and felt by the mother's level of anxiety. Not confirmed suspicions that the
      level of depression in mothers depends on the severity of asthma in children. The
      structure of the relationship between maternal anxiety and depression and other
      characteristics was analyzed in the work differs between groups. Analyzed the
      relationship between the family situation and other variable factors and the
      severity of asthma in children have not been confirmed.

PMID- 25771517
TI  - The occurrence of tumors of the central nervous system in a clinical observation.
AB  - Brain tumor is an abnormal growth of cells in central nervous system (CNS). The
      most common primary brain tumors are: gliomas, meningiomas, pituitary adenomas
      and craniopharyngiomas. The secondary group are metastatic tumors. About 25%
      patients with cancers have metastasis to CNS. AIM: The aim of this study was to
      evaluate the most common symptoms and localization of brain tumors, time from
      first symptoms to diagnosis and patients' survival rate. MATERIALS AND METHODS:
      In this retrospective study 106 patients with primary and metastatic brain tumors
      hospitalized in Military Institute of Medicine from 2007 to 2012 year were
      investigated. RESULTS: The most common cause of metastases to brain is non
      smallcell lung carcinoma. The most frequent symptom of brain tumor is headache
      but very often patients have seizures, vomits, arms and legs weakness. The mean
      time of life for patients with gliomas was 9 month and 13 days for patients with
      brain metastases. CONCLUSIONS: It occurred that patients with primary and
      secondary brain tumors lived shorter than it is described in literature. In group
      of patients with metastases to brain 60% had one or two brain tumors so they
      could be treated with surgery and prognosis for them was better.

PMID- 25771518
TI  - [The level of lipid peroxidation in milk replacer formulas for initial feeding of
      infants].
AB  - The products of lipids oxidation: peroxides, hydroxides, aldehydes, ketones,
      esters, alcohols and others show harmful activity against human organism.
      Presence of the compounds in baby's and children's food creates potential health
      hazard. Many of them cause infant's and children's diarrhoea, also, negatively
      influence development of nervous system, show cytotoxic, mutagenic and
      cancerogenic activity (e.g. malonicdialdehyde, 4-hydroxynonenal and others). AIM:
      The aim of the work was to assess the level of lipids peroxidation in milk
      substitute preparations for initial stage baby feeding, before their end of shelf
      life. MATERIALS AND METHODS: The level of lipids peroxidation measured as TBARS
      (thiobarbituric acid reactive substances) concentrations was determined in 6
      available on the Polish market milk substitute infant formulas. The
      determinations was carried out before the end of the shelf-life after 1,2,3,6,9
      and 12 months after purchase. The level of lipid peroxidation was also determined
      after 3-4 and 21 days post opening. RESULTS: TBARS content in the infants food
      ready to be eaten depended on the time of preparation storage. The highest level
      of lipids peroxidation was observed in all the studied food after 12 months of
      storage and after 21 days after opening of the hermetical wrapping. Various level
      of lipids peroxidation in milk substitutes for infant nutrition resulted from
      different amounts and quality of plant oils used in production (different content
      of mono- and polyunsaturated fatty acids, presence of lack of linoleic and alpha
      linolenic acids).

PMID- 25771519
TI  - [Chromophobe renal cell carcinoma - case report].
AB  - Malignant tumors of the kidney, which the most common is renal cell carcinoma
      (RCC) is diagnosed in Poland in more than 5,000 patients each year. Most cases of
      kidney cancer occurs after the age of 55 years. In men, the risk is 2 times
      higher than in women. Among the various histological subtypes of RCC, 5% of cases
      of chromophobe renal cell carcinoma (chRCC). The 1% is in combination with
      oncocytoma, creating a hybrid chromophobe renal cell carcinoma. The paper
      presents a case report of a patient operated on because of a kidney tumor -
      eosinophilic type of chromophobe cancer. During subsequent care of patients
      experienced a rare complication of this type of tumor, ie. metastasized to the
      paraaortic lymph nodes. Another surgery and radiotherapy were later stages of
      treatment. Discussed in the paper example of a patient with type eosinophilic
      chRCC indicate the variable nature and mileage as compared with typical of the
      tumor, thus requiring increased surveillance oncology. This requires a careful
      approach clinicians at the stage of diagnosis and then treatment and aftercare. 

PMID- 25771520
TI  - [Amyothropic neuralgy of lumbosacral plexus - case report].
AB  - Amyothropic neuralgy is a rare disease witch unknown etiopathogenesis. The main
      popular theory says that inflammatory and immunomodulatory process is connected
      with that disease. Diagnosis is made after exclusion of other causes of plexus
      lumbosacralis damage. The main symptom is neuropathic pain after which there is
      observed muscle weakness and atrophy. ENG/EMG study and MRI are made to confirm
      the diagnosis. In this study we described a case of 52 years old female with
      lower limbs paresis, who was diagnosed few years after first symptoms. Limb
      paresis was preluded by lumbar pain. MRI study revealed central spinal disc
      herniations on L1-2, L2-3, L3-4 levels with dura matter compression, L4-5 spinal
      disc right lateral herniation and synovial cyst. MRI of both lumbar plexuses was
      also normal. EMG study revealed features of bilateral, chronic damage of lower
      legs nerves on lumbar plexus level. Patient was treated with physiotherapy and
      gabapentin with dose of 2x600mg per day. 

PMID- 25771521
TI  - [The role of post-translational modification of fibrinogen in the pathogenesis of
      thrombosis].
AB  - Fibrinogen is a precursor of fibrin, which is the main component of the blood
      clot. The opposite of coagulation is fibrinolysis. The proper functioning of both
      systems allow to maintain a hemostasis. Increasing level of fibrinogen is an
      important risk factor for myocardial infarction or ischemic stroke. Reactive
      oxygen, nitrogen and chlorine species are created in inflammatory conditions,
      ischemia and tissues reperfusion. They can modify the fibrinogen molecule. The
      most important changes are associated with nitration and chlorination of tyrosine
      residues, oxidation of methionine, histidine and tryptophan residues, as well as
      formation dityrosine and carbonyl groups. Moreover, structure of fibrinogen is
      modified by glycation and homocysteinylation in hyperglycemia and
      hyperhomocysteinemia conditions. Non-enzymatic posttranslational modifications of
      fibrinogen contribute to formation of thrombogenic fibrin structure. The degree
      of fibrinogen modification is responsible for fiber structure, packing and
      susceptibility of fibrin clots to fibrinolysis. Additionally, the viscoelastic
      properties are changed. Resistance to fibrinolysis is largely associated with the
      modification of lysine residues in the protein molecule. Each of these
      alternations may contribute to increased risk of arterial and venous thrombosis. 

PMID- 25771522
TI  - [Epidemiology, prevention and risk morbidity factors for lung cancer].
AB  - Lung cancer incidence kept increasing dynamically in male population until the
      late 90s and then there was a sudden drop in the cases and this tendency has been
      maintained up till now. What seems upsetting, however, is the fact that for
      female population there is a constant growth in the lung cancer morbidity.
      Needless to say, Poland still belongs to the countries with high lung cancer
      incidence and lung cancer mortality. In 2011 the standardized morbidity rate in
      Poland accounted for 50,0/100 000 in male population and 17,3/100 000 in female
      population. In Podkarpacie Voivodeship it was 43,6/100 000 for males and 11,8/100
      000 for females respectively. Lung cancer incidence and lung cancer mortality
      seem to increase together with age, and for people 65 and more this type of
      cancer accounts for approximately 50% of all cancer cases and cancer caused
      deaths. In spite of various research conducted and great medical progress little
      can be done to cure lung cancer. The percentage of 5-year survivals increased for
      males from 10,8% in years 2000-2002 to 11,9% in years 2003-2005, and for females
      from 15,7% to 16,9%. The main cause of lung cancer is certainly active and
      passive smoking. It is highly possible that environmental factors are also
      responsible for lung cancer cases. Among the most devastating are such factors as
      asbestos, arsenic, aromatic hydrocarbons, individual lifestyle and nutrition,
      genetic predisposition and finally the pollution, particularly of the air. 

PMID- 25771523
TI  - [The relationship between selected fluid intake and the risk of diabetes].
AB  - Diabetes mellitus is a chronic metabolic disease which affects more and more
      people. It is estimated that in Poland it affects about 2.6 million people, of
      which diagnosed and treated diabetes constitute only 60% cases. The increased
      incidences of diabetes and prediabetes, indicate the need for undertake
      prevention activities and forces for continuous analysis of lifestyle factors
      that may influence the risk of developing the disease. In the thesis it was
      described in detail the relationship between liquids intake such as coffee, tea,
      pure water and sugar-sweetened beverages and risk of the occurrence of type 2
      diabetes. Much research proved that coffee reduces the risk of developing
      diabetes. An inverse relationship has been demonstrated in the case of
      consumption of sugar-sweetened beverages. In relation to tea and pure water due
      to the limited amount of data, there is a need to further research conducting,
      however, there are some evidence that people who consumed less than 0.5 liters of
      water a day should be covered by preventive treatment against diabetes. 

PMID- 25771524
TI  - [A brief history of resuscitation - the influence of previous experience on
      modern techniques and methods].
AB  - Cardiopulmonary resuscitation (CPR) is relatively novel branch of medical
      science, however first descriptions of mouth-to-mouth ventilation are to be found
      in the Bible and literature is full of descriptions of different resuscitation
      methods - from flagellation and ventilation with bellows through hanging the
      victims upside down and compressing the chest in order to stimulate ventilation
      to rectal fumigation with tobacco smoke. The modern history of CPR starts with
      Kouwenhoven et al. who in 1960 published a paper regarding heart massage through
      chest compressions. Shortly after that in 1961Peter Safar presented a paradigm
      promoting opening the airway, performing rescue breaths and chest compressions.
      First CPR guidelines were published in 1966. Since that time guidelines were
      modified and improved numerously by two leading world expert organizations ERC
      (European Resuscitation Council) and AHA (American Heart Association) and
      published in a new version every 5 years. Currently 2010 guidelines should be
      obliged. In this paper authors made an attempt to present history of development
      of resuscitation techniques and methods and assess the influence of previous
      lifesaving methods on nowadays technologies, equipment and guidelines which allow
      to help those women and men whose life is in danger due to sudden cardiac arrest.

PMID- 25771525
TI  - Longitudinal relaxation properties of (1)H(N) and (1)H(alpha) determined by
      direct-detected (13)C NMR experiments to study intrinsically disordered proteins
      (IDPs).
AB  - Intrinsically disordered proteins (IDPs) are functional proteins containing large
      fragments characterized by high local mobility. Bioinformatic studies have
      suggested that a significant fraction (more than 30%) of eukaryotic proteins has
      disordered regions of more than 50 amino acids in length. Hence, NMR methods for
      the characterization of local compactness and solvent accessibility in such
      highly disordered proteins are of high importance. Among the available
      approaches, the HET-SOFAST/BEST experiments (Schanda et al., 2006, Rennella et
      al., 2014) provide semi-quantitative information by monitoring longitudinal (1)H
      relaxation of amide protons under different initial conditions. However, when
      approaching physiological sample conditions, the potential of these amide (1)H
      detected experiments is reduced due to rapid amide proton solvent exchange. (13)C
      direct detection methods therefore provide a valuable alternative thanks to a
      higher chemical shift dispersion and their intrinsic insensitivity toward solvent
      exchange. Here we present two sets of (13)C-detected experiments, which
      indirectly measure (1)H(N) and (1)H(alpha) inversion recovery profiles. The
      experiments consist of an initial spin inversion-recovery block optimized for
      selective manipulation of different types of proton spins followed by a CON read
      out scheme. The proposed experiments were tested on human alpha-synuclein and
      ubiquitin, two representative examples of unfolded and folded proteins. 

PMID- 25771526
TI  - Mechanism for microwave heating of 1-(4'-cyanophenyl)-4-propylcyclohexane
      characterized by in situ microwave irradiation NMR spectroscopy.
AB  - Microwave heating is widely used to accelerate organic reactions and enhance the
      activity of enzymes. However, the detailed molecular mechanism for the effect of
      microwave on chemical reactions is not yet fully understood. To investigate the
      effects of microwave heating on organic compounds, we have developed an in situ
      microwave irradiation NMR spectroscopy. (1)H NMR spectra of 1-(4'-cyanophenyl)-4
      propylcyclohexane (PCH3) in the liquid crystalline and isotropic phases were
      observed under microwave irradiation. When the temperature was regulated at
      slightly higher than the phase transition temperature (Tc=45  degrees C) under a
      gas flow temperature control system, liquid crystalline phase mostly changed to
      the isotropic phase. Under microwave irradiation and with the gas flow
      temperature maintained at 20  degrees C, which is 25  degrees C below the Tc, the
      isotropic phase appeared stationary as an approximately 2% fraction in the liquid
      crystalline phase. The temperature of the liquid crystalline state was estimated
      to be 38  degrees C according to the line width, which is at least 7  degrees C
      lower than the Tc. The temperature of this isotropic phase should be higher than
      45  degrees C, which is considered to be a non-equilibrium local heating state
      induced by microwave irradiation. Microwaves at a power of 195 W were irradiated
      to the isotropic phase of PCH3 at 50  degrees C and after 2 min, the temperature
      reached 220  degrees C. The temperature of PCH3 under microwave irradiation was
      estimated by measurement of the chemical shift changes of individual protons in
      the molecule. These results demonstrate that microwave heating generates very
      high temperature within a short time using an in situ microwave irradiation NMR
      spectrometer.

PMID- 25771527
TI  - Expectation fulfilment and satisfaction in total knee arthroplasty patients using
      the 'PROFEX' questionnaire.
AB  - BACKGROUND: Recent studies have shown that patient reported outcome measures
      (PROMs) may not completely reflect the satisfaction of patients with the
      intervention. The purpose of the study was to develop and validate a novel
      'patient reported fulfilment of expectation' (PROFEX) questionnaire and to study
      the correlation between scores on PROMs (patient reported outcome measures such
      as SF-36 and WOMAC) and the post-operative fulfilment of expectations. MATERIALS
      AND METHODS: In this study, a novel 20-item 'expectation' questionnaire was
      developed, validated and administered pre-operatively to 523 patients who
      underwent total knee arthroplasty for osteoarthritis. The 'fulfilment'
      questionnaire was administered one year following the operation. Physician
      reported (Knee Society Scores) and patient-reported (WOMAC, SF-36) outcome
      measures were also administered. RESULTS: Both components of PROFEX questionnaire
      were found to have good reliability and internal consistency. No significant
      correlation existed between post-operative fulfilment scores and the
      'improvement' scores of WOMAC, SF-36 and Knee Society scores. Lower pre-operative
      expectations were associated with higher post-operative fulfilment scores, but
      the magnitude of this correlation was low. CONCLUSIONS: The lack of correlation
      between the scores on PROMs and the PROFEX scores shows that the scores on the
      PROMs do not reflect the sense of fulfilment of the patients with the outcomes.
      Instruments that directly measure fulfilment of expectations are necessary to
      gain insight into the requirements of the patients.

PMID- 25771528
TI  - Acute traumatic patellar tendon rupture: Early and late results of surgical
      treatment of 38 cases.
AB  - INTRODUCTION: Acute patellar tendon rupture is easy to diagnose but is still
      often overlooked. The aim of this study was to assess early and late results of
      surgical treatment of acute patellar tendon rupture. Our hypothesis was that
      functional outcome is satisfactory. METHODS: A retrospective study included 38
      knees in 37 patients (4 female, 33 male). Mean age was 42.6 +/- 9.9 years (range,
      23-81 years). Lesions comprised 15 tendon body ruptures, 20 avulsions from the
      tip of the patella and 3 avulsions from the anterior tibial tuberosity. Tendon
      repair was protected in more than 95% of cases by a reinforcement frame:
      hamstring (21 cases), synthetic ligament (12 cases) or metallic wire (3 cases).
      Results were evaluated in 2 steps: on patient files at a mean follow-up of 7.1
      months (range, 3-24 months) to assess complications and early functional and
      radiological results; and by phone at a mean follow-up of 9.3 years (range, 19
      229 months) in order to assess long-term functional outcome on Lysholm score and
      patient satisfaction. RESULTS: Thirty-one knees were assessed at a mean 7.1
      months. Mean knee flexion was 128.5 degrees  +/- 7.5 degrees  (range, 85 degrees 
      150 degrees ), extension -1 degrees  (range, -15 degrees  to 0 degrees ) and
      Caton-Deschamps index 0.96 (range, 0.57-1.29). Twenty-three knees were further
      assessed at a mean 9.3 years. Mean Lysholm score was 93.7 points (range, 61-100).
      Ninety-six percent of patients were satisfied or very satisfied with the result.
      All had returned to their previous job, and 20 had returned to sports activities,
      including 8 at pretrauma level. CONCLUSION: Patellar tendon rupture has good
      prognosis if diagnosis and surgical treatment is early.

PMID- 25771529
TI  - Intraoperative 3-dimensional imaging of scaphoid fracture reduction and fixation.
AB  - INTRODUCTION: We examined the clinical benefit of two intraoperative three
      dimensional imaging modalities for reduction and fixation of scaphoid fractures.
      HYPOTHESIS: Our hypothesis was that three dimensional imaging will aid in
      operative care in comparison with standard fluoroscopy. METHODS: In 25
      consecutive patients treated for fractures, after satisfactory reduction and
      fixation was obtained with a single Kirschner wire using fluoroscopy,
      intraoperative three-dimensional visualization was performed. The quality of
      fracture reduction, wire position and extrusion of the wire were examined.
      RESULTS: In two of the 25 cases, after three-dimensional visualization,
      malreduction of the fracture was seen and the reduction revised. Artifact and the
      dependency on technologist performance, limited the use of these modalities to
      locate the wire accurately. DISCUSSION: Diagnosis of malreduction of a scaphoid
      fracture is possible with 3-dimensional modalities. Utilization of these systems
      is still limited by technical factors.

PMID- 25771530
TI  - Evaluation of the pepsin digestibility assay for predicting amino acid
      digestibility of meat and bone meals.
AB  - Sixteen meat and bone meal (MBM) samples were obtained and selected from various
      company plants to provide a wide range in pepsin nitrogen digestibility values.
      Pepsin digestibility was determined using either 0.02 or 0.002% pepsin. Amino
      acid (AA) digestibility of the 16 MBM samples was then determined using a
      precision-fed cecectomized rooster assay. The 0.02% pepsin digestibility values
      were numerically higher than the 0.002% pepsin values. The values varied from 77
      to 93% for 0.02% pepsin and from 67 to 91% for 0.002% pepsin. The rooster AA
      digestibility results showed a wide range of values among MBM samples mostly due
      to the 4 samples having lowest and highest AA digestibility. A precision-fed
      broiler chick ileal AA digestibility assay confirmed that there were large
      differences in AA digestibility among the MBM samples having the lowest and
      highest rooster digestibility values. Correlation analyses between pepsin and AA
      digestibility values showed that the correlation values (r) were highly
      significant (P < 0.0001) for all AA when all 16 MBM samples were included in the
      analysis. However, when the MBM samples with the 2 lowest and the 2 highest
      rooster digestibility values were not included in the correlation analyses, the
      correlation coefficient values (r) were generally very low and not significant (P
      > 0.05). The results indicated that the pepsin nitrogen digestibility assay is
      only useful for detecting large differences in AA digestibility among MBM. There
      also was no advantage for using 0.02 versus 0.002% pepsin. 

PMID- 25771531
TI  - L-arginine upregulates the gene expression of target of rapamycin signaling
      pathway and stimulates protein synthesis in chicken intestinal epithelial cells.
AB  - L-arginine (Arg) is an indispensable amino acid in avians and is required for
      growth. The aim of this study was to investigate the effects of L-Arg on protein
      synthesis and genes expression involved in target of rapamycin (TOR) signaling
      pathway in chicken enterocytes. Cells were cultured for 4 days in L-Arg-free
      Dulbecco's modified Eagle's medium containing 10, 100, 200, 400, or 600 MUM L
      Arg. Cell growth, cell cycle, protein synthesis, and protein degradation as well
      as mRNA expression levels of TOR, ribosomal protein S6 kinase 1 (S6K1), and
      eukaryotic initiation factor 4E-binding protein 1 (4E-BP1) were determined. The
      results showed that cell viability was enhanced by L-Arg with a maximal response
      at 10 to 400 MUM. Increasing extracellular concentrations of L-Arg from 10 to 400
      MUM increased the cells in S and G2/M phase to a significant extent and decreased
      cell numbers in G0/G1 phase. Further more, addition of 100, 200, or 400 MUM L-Arg
      to culture medium increased protein synthesis and reduced protein degradation in
      chicken intestinal epithelial cells. Consistent with the data on cell growth and
      protein turnover, supplementation of 100, 200, or 400 MUM L-Arg increased the
      mRNA abundances of TOR, 4E-BP1, and S6K1. It was concluded the action of L-Arg
      involves in upregulating the genes expression of TOR cell signaling pathway which
      increases protein synthesis and reduces protein degradation. 

PMID- 25771532
TI  - Use of re-esterified oils, differing in their degree of saturation and molecular
      structure, in broiler chicken diets.
AB  - The aim of the present study was to investigate the potential use of re
      esterified oils, differing in their degree of saturation and molecular structure,
      in comparison with their corresponding acid and native oils in broiler chicken
      diets. For this purpose, 144 one-d-old female broiler chickens were randomly
      distributed in 48 cages. Birds were fed a basal diet supplemented with 6% of
      native palm oil ( PN: ), acid palm oil ( PA: ), re-esterified palm oil low in
      mono- ( MAG: ) and diacylglycerols ( DAG: ) ( PEL: ), re-esterified palm oil high
      in MAG and DAG ( PEH: ), native soybean oil ( SN: ), acid soybean oil ( SA: ), re
      esterified soybean oil low in MAG and DAG ( SEL: ), or re-esterified soybean oil
      high in MAG and DAG ( SEH: ), which resulted in a 2 * 4 factorial arrangement.
      Digestibility balances showed that the degree of saturation of fat generally
      exerted a greater impact than did the fat molecular structure. The dietary
      utilization of S sources was higher than that of P sources. However, the
      increased sn-2 saturated fatty acid ( SFA: ) content of EL oils in the starter
      period and the increased MAG and DAG content of EH oils in the grower-finisher
      period yielded favorable effects on the SFA apparent absorption, especially in
      those birds fed re-esterified palm oils. The excreta acylglycerol and free fatty
      acid composition was mainly composed of free fatty acids, and their amount almost
      paralleled the results observed for SFA apparent absorption. For growth
      performance, birds fed S exhibited better feed conversion ratios and lower
      abdominal fat-pad weights than did those fed P. The fatty acid composition of
      abdominal adipose tissue was also mainly affected by the degree of saturation of
      dietary fat sources. We concluded that re-esterified oils, mainly from P sources,
      can be used in broiler chicken diets as alternative fat sources since they show
      similar or even higher total fatty acid apparent absorption than do their
      corresponding native and acid oils, with small changes in abdominal adipose
      tissue fatty acid composition. 

PMID- 25771533
TI  - The effects of long (C20/22) and short (C18) chain omega-3 fatty acids on keel
      bone fractures, bone biomechanics, behavior, and egg production in free-range
      laying hens.
AB  - Keel fractures in the laying hen are the most critical animal welfare issue
      facing the egg production industry, particularly with the increased use of
      extensive systems in response to the 2012 EU directive banning conventional
      battery cages. The current study is aimed at assessing the effects of 2 omega-3
      (n3) enhanced diets on bone health, production endpoints, and behavior in free
      range laying hens. Data was collected from 2 experiments over 2 laying cycles,
      each of which compared a (n3) supplemented diet with a control diet. Experiment 1
      employed a diet supplemented with a 60:40 fish oil-linseed mixture (n3:n6 to
      1.35) compared with a control diet (n3:n6 to 0.11), whereas the n3 diet in
      Experiment 2 was supplemented with a 40:60 fish oil-linseed (n3:n6 to 0.77)
      compared to the control diet (n3:n6 to 0.11). The n3 enhanced diet of Experiment
      1 had a higher n3:n6 ratio, and a greater proportion of n3 in the long chain
      (C20/22) form (0.41 LC:SC) than that of Experiment 2 (0.12 LC:SC). Although
      dietary treatment was successful in reducing the frequency of fractures by
      approximately 27% in Experiment 2, data from Experiment 1 indicated the diet
      actually induced a greater likelihood of fracture (odds ratio: 1.2) and had
      substantial production detriment. Reduced keel breakage during Experiment 2 could
      be related to changes in bone health as n3-supplemented birds demonstrated
      greater load at failure of the keel, and tibiae and humeri that were more
      flexible. These results support previous findings that n3-supplemented diets can
      reduce fracture likely by increasing bone strength, and that this can be achieved
      without detriment to production. However, our findings suggest diets with
      excessive quantities of n3, or very high levels of C20/22, may experience health
      and production detriments. Further research is needed to optimize the quantity
      and type of n3 in terms of bone health and production variables and investigate
      the potential associated mechanisms. 

PMID- 25771534
TI  - Effects of diet, time since defecation, and drying process of the droppings on
      corticosterone metabolite measurements in Japanese quail.
AB  - The use of noninvasive methods for measuring fecal glucocorticoid metabolites is
      a useful tool for endocrine assessment particularly in studies where animals
      cannot be captured, when they should be sampled without disturbing their
      activities, and/or when welfare needs to be maximized. However, still no complete
      standardization exists for the methodology, and some confounding variables may
      play an important role affecting measurements and interpretation of results. The
      present study focused on whether two different diets (laying feed or seed
      mixture), the time since defecation (0, 4, 24, or 48 h) and the drying method of
      those samples (oven-dried or naturally nonoven-dried) may affect concentrations
      of corticosterone metabolites (CM) measured in male Japanese quail. Half of the
      birds were provided with plain water (control) and the other half received a
      corticosterone solution. Birds fed with a seed mixture exhibited higher values of
      CM (nanogram/gram) in droppings than quail that received a laying feed diet
      suggesting that diet should be carefully considered as a potential source of
      variation. As expected both groups exhibited higher CM concentration after
      corticosterone treatment. While CM concentrations increased significantly in
      nonoven-dried samples over time (0 < 4 < 24 = 48 h), oven-dried samples exhibited
      similar high CM values. At 24 and 48 h postdefecation, nonoven-dried samples had
      similar CM concentrations as all oven-dried samples. Drying of samples may be
      considered a reliable method to reduce variations due to water loss over time,
      facilitating comparisons up to 48 h postdefecation. This finding would allow to
      enhance the range of application of this noninvasive and welfare friendly method
      to situations where samples cannot be collected or frozen shortly after
      defecation. 

PMID- 25771535
TI  - Association between dietary cadmium exposure and breast cancer risk: an updated
      meta-analysis of observational studies.
AB  - BACKGROUND: Diet is the primary way cadmium (Cd) enters the body in those without
      occupational exposure and who do not inhabit Cd-polluted regions. Findings on the
      relationship between dietary Cd exposure and breast cancer (BC) risk have been
      inconsistent; a meta-analysis has supported this association but 2 recent cohort
      studies showed inconsistent results. Hence, we performed an updated meta-analysis
      to re-evaluate the association between dietary Cd exposure and BC risk. MATERIAL
      AND METHODS: We searched PubMed, Medline, and EMBASE to identify relevant studies
      published through September 2014. Combined relative risks (RRs) and the
      corresponding 95% confidence intervals (CIs) were used to assess the association
      between dietary Cd exposure and BC risk. RESULTS: We identified 6 studies
      involving 321 315 participants and 11 978 cases. Our study suggested there was no
      statistically significant positive association between dietary Cd exposure and BC
      risk, the combined RR and corresponding 95% CI was 1.01 [0.88, 1.14]. The result
      was not modified by menopause status, geographic area, or study design.
      CONCLUSIONS: Our study did not find a statistically significant positive
      association between dietary Cd exposure and BC risk. It is necessary to
      investigate this relationship among the high-risk groups and more cohort studies
      based on diverse populations are needed.

PMID- 25771536
TI  - Heart failure: focus on co-morbidities, inflammation, and heart rate.

PMID- 25771537
TI  - 'Utterneglect' of rheumatic heart disease revealed by results from global study.

PMID- 25771539
TI  - Kinetic mechanism of protein N-terminal methyltransferase 1.
AB  - The protein N-terminal methyltransferase 1 (NTMT1) catalyzes the transfer of the
      methyl group from the S-adenosyl-l-methionine to the protein alpha-amine,
      resulting in formation of S-adenosyl-l-homocysteine and alpha-N-methylated
      proteins. NTMT1 is an interesting potential anticancer target because it is
      overexpressed in gastrointestinal cancers and plays an important role in cell
      mitosis. To gain insight into the biochemical mechanism of NTMT1, we have
      characterized the kinetic mechanism of recombinant NTMT1 using a fluorescence
      assay and mass spectrometry. The results of initial velocity, product, and dead
      end inhibition studies indicate that methylation by NTMT1 proceeds via a random
      sequential Bi Bi mechanism. In addition, our processivity studies demonstrate
      that NTMT1 proceeds via a distributive mechanism for multiple methylations.
      Together, our studies provide new knowledge about the kinetic mechanism of NTMT1
      and lay the foundation for the development of mechanism-based inhibitors. 

PMID- 25771538
TI  - NsrR from Streptomyces coelicolor is a nitric oxide-sensing [4Fe-4S] cluster
      protein with a specialized regulatory function.
AB  - The Rrf2 family transcription factor NsrR controls expression of genes in a wide
      range of bacteria in response to nitric oxide (NO). The precise form of the NO
      sensing module of NsrR is the subject of controversy because NsrR proteins
      containing either [2Fe-2S] or [4Fe-4S] clusters have been observed previously.
      Optical, Mossbauer, resonance Raman spectroscopies and native mass spectrometry
      demonstrate that Streptomyces coelicolor NsrR (ScNsrR), previously reported to
      contain a [2Fe-2S] cluster, can be isolated containing a [4Fe-4S] cluster. ChIP
      seq experiments indicated that the ScNsrR regulon is small, consisting of only
      hmpA1, hmpA2, and nsrR itself. The hmpA genes encode NO-detoxifying
      flavohemoglobins, indicating that ScNsrR has a specialized regulatory function
      focused on NO detoxification and is not a global regulator like some NsrR
      orthologues. EMSAs and DNase I footprinting showed that the [4Fe-4S] form of
      ScNsrR binds specifically and tightly to an 11-bp inverted repeat sequence in the
      promoter regions of the identified target genes and that DNA binding is abolished
      following reaction with NO. Resonance Raman data were consistent with cluster
      coordination by three Cys residues and one oxygen-containing residue, and
      analysis of ScNsrR variants suggested that highly conserved Glu-85 may be the
      fourth ligand. Finally, we demonstrate that some low molecular weight thiols, but
      importantly not physiologically relevant thiols, such as cysteine and an analogue
      of mycothiol, bind weakly to the [4Fe-4S] cluster, and exposure of this bound
      form to O2 results in cluster conversion to the [2Fe-2S] form, which does not
      bind to DNA. These data help to account for the observation of [2Fe-2S] forms of
      NsrR. 

PMID- 25771541
TI  - [Enantioseparation and determination of atenolol enantiomers in tables on a beta
      cyclodextrin-based chiral stationary phase by high performance liquid
      chromatography].
AB  - A novel dinitrophenyl ether beta-cyclodextrin-bonded chiral stationary phase
      (NESP) for HPLC was prepared with ordered mesoporous SBA-15 as matrix. The fast
      enantioseparation of atenolol enantiomers on the new stationary phase was
      achieved through the optimization of mobile phase composition, column temperature
      and other factors in polar organic solvent mode. The optimized composition of
      mobile phase was acetonitrile/methanol/glacial acetic acid/triethylamine
      (90:10:2.5:3.0, v/v/v/v) at the flow rate of 0.5 mL/min. The column tem- perature
      was set at 20  degrees C. The detection wavelength was 275 nm. The resolution of
      atenolol enantiomers was 1.73 with a rather short analysis time, about 20 min,
      under the above conditions. The atenolol was extracted with methanol from the
      tablets and analyzed by direct injection for HPLC. A new quantitative method of
      atenolol enantiomers in tablets was established after the condition optimization.
      The good linear relationships for two atenolol enantiomers were observed in the
      range of 2.5-100 mg/L with r of 0. 999 2 and 0. 998 9, respectively. The
      recoveries of atenolol enantiomers in tablet samples were 94.60%-97.24%. The
      relative standard deviations (RSDs) of this method were not greater than 0.92%
      for intra-day and 1.86% for inter-day, respectively. The detection limits (S/N =
      3) of concentrations were less than 0.2 mg/L for both enantiomers. The
      established method is simple and of high selectivity, high recovery and low cost
      for enantiomer analysis by using homemade cyclodextrin-based chiral column. It
      has a good application prospect for the fast quality control and the
      pharmacokinetics study of chiral drugs.

PMID- 25771540
TI  - Interdomain hydrophobic interactions modulate the thermostability of microbial
      esterases from the hormone-sensitive lipase family.
AB  - Microbial hormone-sensitive lipases (HSLs) contain a CAP domain and a catalytic
      domain. However, it remains unclear how the CAP domain interacts with the
      catalytic domain to maintain the stability of microbial HSLs. Here, we isolated
      an HSL esterase, E40, from a marine sedimental metagenomic library. E40 exhibited
      the maximal activity at 45  degrees C and was quite thermolabile, with a half
      life of only 2 min at 40  degrees C, which may be an adaptation of E40 to the
      permanently cold sediment environment. The structure of E40 was solved to study
      its thermolability. Structural analysis showed that E40 lacks the interdomain
      hydrophobic interactions between loop 1 of the CAP domain and alpha7 of the
      catalytic domain compared with its thermostable homologs. Mutational analysis
      showed that the introduction of hydrophobic residues Trp(202) and Phe(203) in
      alpha7 significantly improved E40 stability and that a further introduction of
      hydrophobic residues in loop 1 made E40 more thermostable because of the
      formation of interdomain hydrophobic interactions. Altogether, the results
      indicate that the absence of interdomain hydrophobic interactions between loop 1
      and alpha7 leads to the thermolability of E40. In addition, a comparative
      analysis of the structures of E40 and other thermolabile and thermostable HSLs
      suggests that the interdomain hydrophobic interactions between loop 1 and alpha7
      are a key element for the thermostability of microbial HSLs. Therefore, this
      study not only illustrates the structural element leading to the thermolability
      of E40 but also reveals a structural determinant for HSL thermostability. 

PMID- 25771542
TI  - Recommended composition  of influenza virus vaccines for  use in the 2015-2016
      northern  hemisphere influenza season.

PMID- 25771543
TI  - Effects of local anesthetics and calcium on the interaction of cholinergic
      ligands with the nicotinic receptor protein from Torpedo marmorata.
AB  - Studies are presented of the interaction in a physiological ionic environment of
      aromatic amine local anesthetics (prilocaine, lidocaine, and dimethisoquin) and
      Ca++ with receptor-rich membrane fragments isolated from Torpedo electric organ.
      The environmentaly sensitive fluorophore 1-(5-dimethylaminonaphthalene-1
      sulfonamido)ethane 2-trimethylammonium iodide (DNS-chol)interacts with two
      classes of sites in the membrane fragments: the cholinergic receptor site and
      secondary sites characterized by probe emission properties (lambdamax) sensitive
      to the pharmacological nature (agonist or antagonist) of the cholinergic ligand
      bound to the receptor site. Fluorescence studies show that the local anesthetics
      cause an increase of affinity of the membrane-bound receptor for DNS-chol and for
      cholinergic ligands, both agonists and antagonists. The increase of affinity is
      not associated with a change of DNS-chol emission properties. At the same
      concentrations at which the anesthetics control receptor affinity, they also
      affect the fluorescence of DNS-chol bound to the secondary sites: the presence of
      local anesthetic causes a loss of the DNS-chol spectral properties characteristic
      of the binding of agonists to the receptor site. Local anesthetics also control
      the binding of [3H]acetylcholine to the membrane-bound receptor. In the absence
      of prilocaine the acetylcholine binding curve is slightly sigmoid (Hill
      coefficient, nH = 1.4, half-saturation at 10 nM free acetylcholine). In the
      presence of 3 mM prilocaine there is a decrease of cooperativity and an increase
      of affinity (nH = 1.0, half-saturation at 6 mM free acetylcholine). The
      concentrations at which the local anesthetics act on the membrane fragments are
      those at which they block the permeability response of Electrophorus electroplax
      upon addition to the bath of the agonist carbamylcholine. Fluorescence and
      radioactive ligand assays demonstrate that Ca++ also causes an increase of
      receptor affinity for cholinergic ligands, but in a manner significantly
      different from that observed with local anesthetics. Solubilization of membrane
      fragments by detergent leads to changes in the binding properties of the receptor
      protein. On the membrane fragments the binding data for each agonist can be
      analyzed in terms of a homogeneous population of sites, while after
      solubilization heterogeneity of the binding constants appears. Prilocaine or Ca+
      no longer affects the binding of acetylcholine to the solubilized receptor
      protein. The observed effects of local anesthetics and Ca++ on the affinity of
      the cholinergic receptor are related to the phenomenon of receptor
      desensitization.

PMID- 25771544
TI  - Medicaid copayments.

PMID- 25771545
TI  - Medicaid provider tax.

PMID- 25771546
TI  - Medicaid waivers.

PMID- 25771547
TI  - Benefits and services.

PMID- 25771548
TI  - Federal Medicaid policy.

PMID- 25771549
TI  - Medicaid reimbursement.

PMID- 25771550
TI  - Medicaid restructuring.

PMID- 25771551
TI  - Managed care.

PMID- 25771552
TI  - Mandated benefits.

PMID- 25771553
TI  - Pharmaceuticals and medical devices: cost savings.

PMID- 25771554
TI  - Pharmaceuticals and medical devices: Medicare Part D.

PMID- 25771555
TI  - Pharmaceuticals and medical devices: business practices.

PMID- 25771556
TI  - The evaluation of a 2D diode array in "magic phantom" for use in high dose rate 
      brachytherapy pretreatment quality assurance.
AB  - PURPOSE: High dose rate (HDR) brachytherapy is a treatment method that is used
      increasingly worldwide. The development of a sound quality assurance program for
      the verification of treatment deliveries can be challenging due to the high
      source activity utilized and the need for precise measurements of dwell positions
      and times. This paper describes the application of a novel phantom, based on a 2D
      11 * 11 diode array detection system, named "magic phantom" (MPh), to accurately
      measure plan dwell positions and times, compare them directly to the treatment
      plan, determine errors in treatment delivery, and calculate absorbed dose.
      METHODS: The magic phantom system was CT scanned and a 20 catheter plan was
      generated to simulate a nonspecific treatment scenario. This plan was delivered
      to the MPh and, using a custom developed software suite, the dwell positions and
      times were measured and compared to the plan. The original plan was also
      modified, with changes not disclosed to the primary authors, and measured again
      using the device and software to determine the modifications. A new metric, the
      "position-time gamma index," was developed to quantify the quality of a treatment
      delivery when compared to the treatment plan. The MPh was evaluated to determine
      the minimum measurable dwell time and step size. The incorporation of the TG-43U1
      formalism directly into the software allows for dose calculations to be made
      based on the measured plan. The estimated dose distributions calculated by the
      software were compared to the treatment plan and to calibrated EBT3 film, using
      the 2D gamma analysis method. RESULTS: For the original plan, the magic phantom
      system was capable of measuring all dwell points and dwell times and the majority
      were found to be within 0.93 mm and 0.25 s, respectively, from the plan. By
      measuring the altered plan and comparing it to the unmodified treatment plan, the
      use of the position-time gamma index showed that all modifications made could be
      readily detected. The MPh was able to measure dwell times down to 0.067 +/- 0.001
      s and planned dwell positions separated by 1 mm. The dose calculation carried out
      by the MPh software was found to be in agreement with values calculated by the
      treatment planning system within 0.75%. Using the 2D gamma index, the dose map of
      the MPh plane and measured EBT3 were found to have a pass rate of over 95% when
      compared to the original plan. CONCLUSIONS: The application of this magic phantom
      quality assurance system to HDR brachytherapy has demonstrated promising ability
      to perform the verification of treatment plans, based upon the measured dwell
      positions and times. The introduction of the quantitative position-time gamma
      index allows for direct comparison of measured parameters against the plan and
      could be used prior to patient treatment to ensure accurate delivery.

PMID- 25771557
TI  - Light output measurements and computational models of microcolumnar CsI 
      scintillators for x-ray imaging.
AB  - PURPOSE: The authors report on measurements of light output and spatial
      resolution of microcolumnar CsI:Tl scintillator detectors for x-ray imaging. In
      addition, the authors discuss the results of simulations aimed at analyzing the
      results of synchrotron and sealed-source exposures with respect to the
      contributions of light transport to the total light output. METHODS: The authors
      measured light output from a 490-MUm CsI:Tl scintillator screen using two setups.
      First, the authors used a photomultiplier tube (PMT) to measure the response of
      the scintillator to sealed-source exposures. Second, the authors performed
      imaging experiments with a 27-keV monoenergetic synchrotron beam and a slit to
      calculate the total signal generated in terms of optical photons per keV. The
      results of both methods are compared to simulations obtained with hybridmantis, a
      coupled x-ray, electron, and optical photon Monte Carlo transport package. The
      authors report line response (LR) and light output for a range of linear
      absorption coefficients and describe a model that fits at the same time the light
      output and the blur measurements. Comparing the experimental results with the
      simulations, the authors obtained an estimate of the absorption coefficient for
      the model that provides good agreement with the experimentally measured LR.
      Finally, the authors report light output simulation results and their dependence
      on scintillator thickness and reflectivity of the backing surface. RESULTS: The
      slit images from the synchrotron were analyzed to obtain a total light output of
      48 keV-1 while measurements using the fast PMT instrument setup and sealed
      sources reported a light output of 28 keV-1. The authors attribute the difference
      in light output estimates between the two methods to the difference in time
      constants between the camera and PMT measurements. Simulation structures were
      designed to match the light output measured with the camera while providing good
      agreement with the measured LR resulting in a bulk absorption coefficient of 5 *
      10-5MUm-1. CONCLUSIONS: The combination of experimental measurements for
      microcolumnar CsI:Tl scintillators using sealed-sources and synchrotron exposures
      with results obtained via simulation suggests that the time course of the
      emission might play a role in experimental estimates. The procedure yielded an
      experimentally derived linear absorption coefficient for microcolumnar Cs:Tl of 5
      * 10-5MUm-1. To the author's knowledge, this is the first time this parameter has
      been validated against experimental observations. The measurements also offer
      insight into the relative role of optical transport on the effective optical
      yield of the scintillator with microcolumnar structure.

PMID- 25771558
TI  - Computer aided wireless capsule endoscopy video segmentation.
AB  - PURPOSE: Wireless capsule endoscopy (WCE) opens a new door for the digestive
      tract examination and diagnosis. However, the examination of its video data is
      tedious. This study aims to assist a physician to interpret a WCE video by
      segmenting it into different anatomic parts in the digestive tract. METHODS: A
      two level WCE video segmentation scheme is proposed to locate the boundary
      between the stomach, small intestine, and large intestine. In the rough level,
      the authors utilize color feature to draw a dissimilarity curve for a WCE video
      and obtain an approximate boundary. Meanwhile, training data for the fine level
      segmentation can be collected automatically between the two approximate
      boundaries of organs to overcome the difficulty of training data collection in
      traditional approaches. In the fine level, color histogram in the HSI color space
      is used to segment the stomach and small intestine. Then, color uniform local
      binary pattern (CULBP) algorithm is applied for discrimination of the small
      intestine and large intestine, which includes two patterns, namely, color norm
      and color angle pattern. The CULBP feature is robust to variation of illumination
      and discriminative for classification. In order to increase the performance of
      support vector machine, the authors integrate it with the Adaboost approach.
      Finally, the authors refine the classification results to segment a WCE video
      into different parts, that is, the stomach, small intestine, and large intestine.
      RESULTS: The average precision and recall are 91.2% and 90.6% for the
      stomach/small intestine classification, 89.2% and 88.7% for the small/large
      intestine discrimination. Paired t-test also demonstrates a significant better
      performance of the proposed scheme compared to some traditional methods. The
      average segmentation error is 8 frames for the stomach/small intestine
      discrimination, and 14 frames for the small/large intestine segmentation.
      CONCLUSIONS: The results have demonstrated that the new video segmentation method
      can accurately locate the boundary between different organ regions in a WCE
      video. Such a segmentation result may enhance the efficiency of WCE examination.

PMID- 25771559
TI  - Dose reduction of scattered photons from concrete walls lined with lead: 
      Implications for improvement in design of megavoltage radiation therapy  facility
      mazes.
AB  - PURPOSE: This study explores the possibility of using lead to cover part of the
      radiation therapy facility maze walls in order to absorb low energy photons and
      reduce the total dose at the maze entrance of radiation therapy rooms. METHODS:
      Experiments and Monte Carlo simulations were utilized to establish the
      possibility of using high-Z materials to cover the concrete walls of the maze in
      order to reduce the dose of the scatteredphotons at the maze entrance. The dose
      of the backscatteredphotons from a concrete wall was measured for various
      scattering angles. The dose was also calculated by the FLUKA and EGSnrc Monte
      Carlo codes. The FLUKA code was also used to simulate an existing radiotherapy
      room to study the effect of multiple scattering when adding lead to cover the
      concrete walls of the maze. Monoenergetic photons were used to represent the main
      components of the x ray spectrum up to 10 MV. RESULTS: It was observed that when
      the concrete wall was covered with just 2 mm of lead, the measured dose rate at
      all backscattering angles was reduced by 20% for photons of energy comparable to
      Co-60 emissions and 70% for Cs-137 emissions. The simulations with FLUKA and EGS
      showed that the reduction in the dose was potentially even higher when lead was
      added. One explanation for the reduction is the increased absorption of
      backscatteredphotons due to the photoelectric interaction in lead. The results
      also showed that adding 2 mm lead to the concrete walls and floor of the maze
      reduced the dose at the maze entrance by up to 90%. CONCLUSIONS: This novel
      proposal of covering part or the entire maze walls with a few millimeters of lead
      would have a direct implication for the design of radiation therapy facilities
      and would assist in upgrading the design of some mazes, especially those in
      facilities with limited space where the maze length cannot be extended to
      sufficiently reduce the dose.

PMID- 25771560
TI  - Local patient dose diagnostic reference levels in pediatric interventional
      cardiology  in Chile using age bands and patient weight values.
AB  - PURPOSE: To present the results of a patient dose evaluation program in pediatric
      cardiology and propose local diagnostic reference levels (DRLs) for different
      types of procedure and age range, in addition to suggesting approaches to
      correlate patient dose values with patient weight. This study was the first
      conducted in Latin America for pediatric interventional cardiology under the
      auspices of the International Atomic Energy Agency. METHODS: Over three years,
      the following data regarding demographic and patient dose values were collected:
      age, gender, weight, height, number of cine series, total number of cine frames,
      fluoroscopy time (FT), and two dosimetric quantities, dose-area product (DAP) and
      cumulative dose (CD), at the patient entrance reference point. The third quartile
      values for FT, DAP, CD, number of cine series, and the DAP/body weight ratio were
      proposed as the set of quantities to use as local DRLs. RESULTS: Five hundred and
      seventeen patients were divided into four age groups. Sample sizes by age group
      were 120 for <1 yr; 213 for 1 to <5 yr; 82 for 5 to <10 yr; and 102 for 10 to <16
      yr. The third quartile values obtained for DAP by diagnostic and therapeutic
      procedures and age range were 1.17 and 1.11 Gy cm2 for <1 yr; 1.74 and 1.90 Gy
      cm2 for 1 to <5 yr; 2.83 and 3.22 Gy cm2 for 5 to <10 yr; and 7.34 and 8.68 Gy
      cm2 for 10 to <16 yr, respectively. The third quartile value obtained for the
      DAP/body weight ratio for the full sample of procedures was 0.17 (Gy cm2/kg) for
      diagnostic and therapeutic procedures. CONCLUSIONS: The data presented in this
      paper are an initial attempt at establishing local DRLs in pediatric
      interventional cardiology, from a large sample of procedures for the standard age
      bands used in Europe, complemented with the values of the ratio between DAP and
      patient weight. This permits a rough estimate of DRLs for different patient
      weights and the refining of these values for the age bands when there may be
      large differences in child size. These DRLs were obtained at the largest
      pediatric hospital in Chile, with an active optimization program, and could be
      used by other hospitals in the Latin America region to compare their current
      patient dose values and determine whether corrective action is appropriate.

PMID- 25771561
TI  - Application of the diagnostic radiological index of protection  to protective
      garments.
AB  - PURPOSE: Previously, the diagnostic radiological index of protection (DRIP) was
      proposed as a metric for quantifying the protective value of radioprotective
      garments. The DRIP is a weighted sum of the percent transmissions of different
      radiation beams through a garment. Ideally, the beams would represent the
      anticipated stray radiation encountered during clinical use. However, it is
      impractical to expect a medical physicist to possess the equipment necessary to
      accurately measure transmission of scatteredradiation. Therefore, as a proof of
      concept, the authors tested a method that applied the DRIP to clinical practice.
      METHODS: Primary beam qualities used in interventional cardiology and radiology
      were observed and catalogued. Based on the observed range of beam qualities, five
      representative clinical primary beam qualities, specified by kV and added
      filtration, were selected for this evaluation. Monte Carlo simulations were
      performed using these primary beams as source definitions to generate
      scatteredspectra from the clinical primary beams. Using numerical optimization,
      ideal scatter mimicking primary beams, specified by kV and added aluminum
      filtration, were matched to the scatteredspectra according to half- and quarter
      value layers and spectral shape. To within reasonable approximation, these
      theoretical scatter-mimicking primary beams were reproduced experimentally in
      laboratory x ray beams and used to measure transmission through pure lead and
      protective garments. For this proof of concept, the DRIP for pure lead and the
      garments was calculated by assigning equal weighting to percent transmission
      measurements for each of the five beams. Finally, the areal density of lead and
      garments was measured for consideration alongside the DRIP to assess the
      protective value of each material for a given weight. RESULTS: The authors
      identified ideal scatter mimicking primary beams that matched scatteredspectra to
      within 0.01 mm for half- and quarter-value layers in copper and within 5% for the
      shape function. The corresponding experimental scatter-mimicking primary beams
      matched the Monte Carlo generated scatteredspectra with maximum deviations of
      6.8% and 6.6% for half- and quarter-value layers. The measured DRIP for 0.50 mm
      lead sheet was 2.0, indicating that it transmitted, on average, 2% of incident
      radiation. The measured DRIP for a lead garment and one lead-alternative garment
      closely matched that for pure lead of 0.50 mm thickness. The DRIP for other
      garments was substantially higher than 0.50 mm lead (3.9-5.4), indicating they
      transmitted about twice as much radiation. When the DRIP was plotted versus areal
      density, it was clear that, of the garments tested, none were better than lead on
      a weight-by-weight basis. CONCLUSIONS: A method for measuring the DRIP for
      protective garments using scatter-mimicking primary beams was developed. There
      was little discernable advantage in protective value per unit weight for lead
      alternative versus lead-only garments. Careful consideration must be given to the
      balance of protection and weight when choosing a lead-alternative protective
      garment with a lower specified "lead equivalence," e.g., 0.35 mm. The DRIP has
      the potential to resolve this dilemma. Reporting the DRIP relative to areal
      density is an ideal metric for objective comparisons of protective garment
      performance, considering both protective value in terms of transmission of
      radiation and garment weight.

PMID- 25771562
TI  - Abstracts of the 7th Croatian Congress of Nephrology, Dialysis and
      Transplantation, October 10-12, 2014, Pula, Croatia.

PMID- 25771564
TI  - Proceedings of the 12th Conference on Neurovascular Events after Subarachnoid
      Hemorrhage, July 10-12, 2013, Lucerne, Switzerland.

PMID- 25771563
TI  - [Proceedings of the 77th National Congress SIMLII, October 15-17, 2014, Bologna,
      Italy].

PMID- 25771565
TI  - Addictions are the nation's #1 public health crisis.

PMID- 25771566
TI  - 10 marketing must-haves.

PMID- 25771567
TI  - Marketing must-have #10.

PMID- 25771568
TI  - One CEO attacks bait-and-switch marketing.

PMID- 25771569
TI  - Traumatic brain injury treatment includes behavioral health.

PMID- 25771570
TI  - 7 ways to break up with paper.

PMID- 25771571
TI  - Be wary of copy-and-paste EHR mistakes.

PMID- 25771572
TI  - Global-pay model aims to fully integrate behavioral health.

PMID- 25771573
TI  - Consider the market before expanding to new locations.

PMID- 25771574
TI  - Consider the psychology of color for both form and function.

PMID- 25771575
TI  - Vermont Psychiatric Care Hospital rebuilds after hurricane.

PMID- 25771576
TI  - [The importance of words].

PMID- 25771577
TI  - [Advanced practice nurses, first phase of work].

PMID- 25771578
TI  - [Medication in single packs, vigilance is essential].

PMID- 25771579
TI  - [A supplement to the nursing degree].

PMID- 25771580
TI  - [Maternal and infant protection, advice from the Economic, Social and
      Environmental Council].

PMID- 25771581
TI  - [A national week to celebrate the health of women and children].

PMID- 25771582
TI  - [How to better recognize child abuse].

PMID- 25771583
TI  - [Honoring the young who help others].

PMID- 25771584
TI  - [A reduction of environmental pollution exposure].

PMID- 25771585
TI  - [Signing the 3rd protocol of the Convention of the Rights of Children by France].

PMID- 25771586
TI  - [Antibacterial resistance of intestinal flora].

PMID- 25771587
TI  - [Simple and comprehensive food labeling].

PMID- 25771588
TI  - [The blue jackets of the AP-HP].

PMID- 25771589
TI  - [Progress in the prevention of HIV in children].

PMID- 25771590
TI  - [Overweight adolescents, a better quality of life after losing weight].

PMID- 25771591
TI  - [Automutilation in adolescence, a mental risk factor in adult age].

PMID- 25771592
TI  - [Children and digital media. A digital revolution].

PMID- 25771593
TI  - [Growing up in the digital age].
AB  - Virtual reality is at the heart of our daily lives at every age. The
      proliferation of screens and their use at an ever earlier age requires reflection
      on how to give the best possible support to children and teenagers with regard to
      their modern virtual practices. Health professionals have their role to play in
      combining their knowledge of these age groups with in-depth understanding of the
      issues surroundingvirtual realities.

PMID- 25771594
TI  - [From the "screen" society to concern for future generations].
AB  - The youth of today is evolving in an unprecedented sociocultural context marked
      by the rapid development of new virtual technologies. Young people are constantly
      looking at screens, big and small, tactile and digital, which have invaded their
      social sphere. Connected, logged on, overstimulated, the new generation lives
      surrounded by reactivity and electronic interactions. It is adults'
      responsibility to expand the range of their cultural and outdoor activities in
      order to avoid the risk of their capacity for personal expression wasting away.

PMID- 25771595
TI  - [The impact of digital media on relations, play and learning in young children].
AB  - Screens are occupying an increasingly bigger place in families, which can have
      harmful consequences on the development of young children. To ensure their
      harmonious construction, children must not be deprived of games which involve
      interaction with the outside world and adults. They need exchanges with their
      parents and with professionals aware of the role which they have to play in a
      child's discoveries.

PMID- 25771596
TI  - [The need for education and regulation regarding the use of digital media].
AB  - Children and teenagers spend vast amounts of time in front of screens. Faced with
      this reality, it is essential that they receive media education to help them get
      a proper grasp of information and image cultures. It is designed to offer global
      support for their cognitive, emotional and social construction and requires the
      participation all those who play a role in their education: their family,
      teachers and extracurricular activity leaders.

PMID- 25771597
TI  - [Switching off digital media to learning how to use it responsibly].
AB  - The 'Screen-free Challenge' has been experienced in almost 200 schools across
      France, generally on the initiative of parents and teachers. The objective is to
      make children and teenagers aware of their use of screens and support screen
      replacement with leisure and sports activities, during a given period of time.
      This initiative has been a huge success and has produced significant results,
      notably in terms of improving learning, preventing obesity and decrease of
      violence.

PMID- 25771598
TI  - [Bibliography. Children and digital media].

PMID- 25771599
TI  - [A professional workshop for the transfer of knowledge].
AB  - Nurses from the surgical unit of Robert-Debre hospital in Paris have put in place
      a professional practices workshop in order to pass on their knowledge and
      expertise in highly technical nursing procedures, such as tracheotomies, stomata
      or central venous lines. This approach helps to maintain an optimal level of
      competency and to standardise practices.

PMID- 25771600
TI  - [Caring for a child born anonymously in the nursery].
AB  - Every year, some children born anonymously are cared for in the neonatology units
      which health professionals sometimes find difficult. Team discussions, the
      creation of networks and the provision of developmental care, in particular,
      constitute tools for constructing a high-quality, multi-disciplinary support
      strategy.

PMID- 25771601
TI  - Think of quality health care when casting your vote.

PMID- 25771602
TI  - Development of a team-based method for assuring the quality of assistive
      technology documentation.
AB  - Good practice in assistive technology (AT) service delivery targeting children
      with disabilities has come increasingly to include providing AT stakeholders with
      a final text record that documents the rationale and procedures behind the
      recommendations made during the AT assessment process (AT documentation). In the
      present case study of one AT service provider, we developed a team-based approach
      for conducting an evaluation of the quality of the AT documentation. A service
      specific scale for the evaluation of AT documentation was developed following a
      five-step approach. The scale was employed to'review AT documentation utilizing
      specific review criteria in order to evaluate the quality of AT documentation
      practices with regard to the service investigated. Two independent reviewers
      examined the AT documentation for 130 cases of AT service provision. Weighted
      kappa and Intraclass correlation coefficients (ICC) were employed as a measure of
      inter-rater agreement. The results of the documentation evaluation allowed AT
      professionals to objectively assess the quality of the AT documentation produced
      by the service under investigation, identify shortcomings in the documentation
      process, and make related corrections. AT services may benefit from the
      employment of strategic approaches for the evaluation of service provision.
      Possible applications to other AT service providers are discussed.

PMID- 25771603
TI  - Electronic bracelet and vision-enabled waist-belt for mobility of visually
      impaired people.
AB  - A wearable assistive system is proposed to improve mobility of visually impaired
      people (subjects). This system has been implemented in the shape of a bracelet
      and waist-belt in order to increase its wearable convenience and cosmetic
      acceptability. A camera and an ultrasonic sensor are attached to a customized
      waist-belt and bracelet, respectively. The proposed modular system will act as a
      complementary aid along with a white cane. Its vision-enabled waist-belt module
      detects the path and distribution of obstacles on the path. This module conveys
      the required information to a subject via a mono earphone by activating relevant
      spoken messages. The electronic bracelet module assists the subject to verify
      this information and to perceive distance of obstacles along with their
      locations. The proposed complementary system provides an improved understanding
      of the surrounding environment with less cognitive and perceptual efforts as
      compared to a white cane alone. This system was subjected to clinical evaluations
      with 15 totally blind subjects. Results of usability experiments demonstrated
      effectiveness of the system as a mobility aid. Amongst the participated subjects,
      93.33% expressed satisfaction with the information content of this system, 86.66%
      subjects comprehended its operational convenience, and 80% appreciated the
      comfort of the system.

PMID- 25771604
TI  - Accessible engineering drawings for visually impaired machine operators.
AB  - An engineering drawing provides manufacturing information to a machine operator.
      An operator plans and executes machining operations based on this information. A
      visually impaired (VI) operator does not have direct access to the drawings.
      Drawing information is provided to them verbally or by using sample parts. Both
      methods have limitations that affect the quality of output. Use of engineering
      drawings is a standard practice for every industry; this hampers employment of a
      VI operator. Accessible engineering drawings are required to increase both
      independence, as well as, employability of VI operators. Today, Computer Aided
      Design (CAD) software is used for making engineering drawings, which are saved in
      CAD files. Required information is extracted from the CAD files and converted
      into Braille or voice. The authors of this article propose a method to make
      engineering drawings information directly accessible to a VI operator.

PMID- 25771605
TI  - Evaluating the image quality of Closed Circuit Television magnification systems
      versus a head-mounted display for people with low vision. .
AB  - In this research, image analysis was used to optimize the visual output of a
      traditional Closed Circuit Television (CCTV) magnifying system and a head-mounted
      display (HMD) for people with low vision. There were two purposes: (1) To
      determine the benefit of using an image analysis system to customize image
      quality for a person with low vision, and (2) to have people with low vision
      evaluate a traditional CCTV magnifier and an HMD, each customized to the user's
      needs and preferences. A CCTV system can electronically alter images by
      increasing the contrast, brightness, and magnification for the visually disabled
      when they are reading texts and pictures. The test methods was developed to
      evaluate and customize a magnification system for persons with low vision. The
      head-mounted display with CCTV was used to obtain better depth of field and a
      higher modulation transfer function from the video camera. By sensing the
      parameters of the environment (e.g., ambient light level, etc.) and collecting
      the user's specific characteristics, the system could make adjustments according
      to the user's needs, thus allowing the visually disabled to read more
      efficiently.

PMID- 25771606
TI  - Transit apps for people with brain injury and other cognitive disabilities: the
      state of the art.
AB  - Individuals with cognitive disability have difficulty using public transit, but
      little research is directed toward this issue. Recent studies suggest that
      smartphones may be useful assistive devices in this context. Current objectives
      were to (1) survey research into difficulties people with cognitive disabilities
      experience when using public transit, (2) survey the current state of the art of
      transit and personal navigation applications (apps) and features, (3) recommend
      best existing transit apps for people with cognitive disability, and (4)
      recommend the best designs and features of these apps to developers of future
      transit apps. Potentially useful features were found in four categories: Transit
      apps for (1) individuals with cognitive disabilities and (2) healthy individuals,
      and personal navigation apps for (3) individuals with cognitive disabilities and
      (4) healthy individuals. A total of 159 apps were examined, but only seven were
      found specific to public transit for cognitive disability. By comparing research
      recommendations and currently available features, we identified several unmet
      needs. We note that there appears to be a shortage of apps for this population
      function but that there is good research in the area and it is well suited to
      inform app development.

PMID- 25771607
TI  - A detachable electronic device for use with a long white cane to assist with
      mobility.
AB  - Vision-impaired individuals often use a long white cane to assist them with
      gathering information about their surroundings. However, these aids are generally
      not used to detect obstacles above knee height. The purpose of this study is to
      determine whether a low-cost, custom-built electronic device clipped onto a
      traditional cane can provide adequate vibratory warning to the user of obstacles
      above knee height. Sixteen normally sighted blindfolded individuals participated
      in two mobility courses which they navigated using a normal white cane and a
      white cane with the electronic device attached. Of the 16 participants, 10 hit
      fewer obstacles, and 12 covered less ground with the cane when the electronic
      device was attached. Ten participants found navigating with the electronic device
      easier than just the white cane alone. However, the time taken on the mobility
      courses, the number of collisions with obstacles, and the area covered by
      participants using the electronic device were not significantly different (p >
      0.05). A larger sample size is required to determine if the trends found have
      real significance. It is anticipated that additional information provided by this
      electronic device about the surroundings would allow users to move more
      confidently within their environment.

PMID- 25771609
TI  - Buttermilk is good for what ails Farmer Jones.

PMID- 25771608
TI  - Can Braille be revived? A possible impact of high-end Braille and mainstream
      technology on the revival of tactile literacy medium.
AB  - With a decline in use of Braille, very few attractive technological options can
      be offered to young learners. Various research data confirm that teachers of the
      visually impaired do not have sufficient skills to introduce their students to
      modern devices. The Mountbatten Brailler can be considered as a tool that
      combines Braille technology with mainstream tools commonly used by students and
      teachers. This combination of devices opens new possibilities for the teachers
      and their students to reverse the trend in the use of Braille. Thanks to features
      offered by the Brailler and iOS devices, sighted and blind users receive a tool
      for unimpaired written communication.

PMID- 25771610
TI  - Five inadvertent HIPAA violations by physicians.

PMID- 25771611
TI  - Relevance of linguistic and cultural training among non-clinical personnel at the
      University of Mississippi Medical Center: a qualitative study.
AB  - BACKGROUND: An academic medical center presents a unique environment where non
      clinical staff provide vital services to a cross-section of people. A medical
      Spanish course was offered to a non-clinical department, campus police, in
      response to the growing number of Hispanics or Latinos seeking care within the
      health center. METHOD: In October 2007, a structured group discussion with six
      course participants was convened at the end of the Occupational Spanish course,
      using a topic guide to direct the conversation. RESULTS: Content analysis
      revealed that participation in the course: (1) increased interest and provided a
      model for other departments, (2) promoted ability to respond, (3) enhanced
      cultural and linguistic competence, and (4) increased confidence, effectiveness,
      and value in their work. CONCLUSIONS: Structured cultural and linguistic training
      within an academic health center can contribute to a safe, secure environment, a
      more competent, responsive workforce, and enhance services to limited English
      proficient (LEP) patients.

PMID- 25771613
TI  - President's Page. The season of change.

PMID- 25771612
TI  - Prognostic value of cardiac-specific troponins in chronic obstructive pulmonary
      disease exacerbations: a systematic review.
AB  - fer useful prognostic information in this population and might identify a group
      of patients to target for more intensive thera- peutic interventions. BACKGROUND:
      Cardiac troponins are specific and sensitive biomarkers used for diagnosis and
      prognosis in myocardial infarction. Troponin elevations can also occur in other
      disorders and may be useful to predict mortality. This systematic review is
      intended to determine whether or not elevated troponins are predictive of
      mortality (in-hospital, short term, and longer-term) among patients admitted with
      COPD exacerbation. METHODS: PubMed/Medline was searched to identify relevant
      English language articles that measured troponin T or troponin I in patients
      hospitalized for COPD exacerbation and assessed mortality, with or without other
      clinical outcomes. Only studies of significant size that presented original data
      were included. RESULTS: Nine research reports (4 prospective, 5 retrospective)
      qualified for review. Mortality was consistently increased in seven of these
      studies among COPD patients who had elevated troponin levels during an
      exacerbation. One retrospective study found no effect on (in-hospital) mortality
      but reported increased morbidity (greater oxygen requirements and more
      ventilatory failure) and increased length of hospital stay in patients with
      elevated troponin whereas discharge troponin T in one prospective study predicted
      hospitalizations. CONCLUSIONS: The review shows a strong direct association
      between cardiac troponin and mortality in patients hospitalized for COPD
      exacerbations. Troponin monitoring could offer useful prognostic information in
      this population and might identify a group of patients to target for more
      intensive therapeutics interventions.

PMID- 25771614
TI  - Health department recognizes Mississippi accomplishments.

PMID- 25771615
TI  - Positions on Medicaid expansion and response.

PMID- 25771616
TI  - Editor's response to positions on Medicaid expansion.

PMID- 25771617
TI  - When life presents a lemon, make lemonade.

PMID- 25771618
TI  - Vegetarian hunting in Garlandsville, Mississippi.

PMID- 25771619
TI  - Reaching the finish line with dignity.

PMID- 25771620
TI  - How early elective deliveries impact infant health in Mississippi.
AB  - BACKGROUND: Infants delivered early for non-medical reasons are at increased risk
      of poor birth outcomes. Trends and associated health outcomes were unexamined in
      Mississippi. OBJECTIVE: Determine elective delivery trends and impacts on infant
      mortality. METHODS: Identify cesarean deliveries and inductions without medical
      indications from birth certificate records linked with death certificate records.
      Assess differences in death rates between those born electively during 37 and 38
      weeks compared to 39 weeks gestation. RESULTS: Early elective delivery rates
      increased significantly (p < .01) from 8.5% in 2001 to a peak of 17.8% in 2008.
      The rate began to decline in 2008 and was 16.5% in 2011. Neonates born electively
      before 39 weeks gestation had three-fold higher death rates [2.1 per 1,000] than
      neonates born at 39 weeks gestation [0.6 per 1,000], a statistically significant
      difference. CONCLUSION: Early elective deliveries in Mississippi are associated
      with increased infant mortality. Reducing this common practice could improve
      birth outcomes in the state.

PMID- 25771621
TI  - Progress in the early identification of hearing impaired infants in Mississippi.
AB  - The prevalence of permanent congenital hearing loss is three to four infants per
      thousand live births. Because early intervention is effective in preventing
      speech and language delay, the NIH has recommended universal newborn hearing
      screening. Prior to this recommendation, several states, including Mississippi
      which had one of the first hospital based screening programs, had statewide
      programs. In 1981 the Lions Clubs of Mississippi and the University of
      Mississippi Medical Center began an infant hearing screening program, which was
      described in Volume XXX of The Journal of the Mississippi State Medical
      Association. This program was recognized in 1986 with an award from the U.S.
      Secretary of Health and Human Services, and by 1989, the Lions Club had persuaded
      twenty-two hospitals that this was a needed service. Twelve years after the start
      of the program in Mississippi, the National Institutes of Health (NIH)
      recommended universal newborn hearing screening. This article reviews
      Mississippi's efforts toward early identification of hearing loss and provides an
      update on the current screening program.

PMID- 25771622
TI  - "I keep falling all the time..." .

PMID- 25771624
TI  - Farewell address.

PMID- 25771623
TI  - An interview with Claude D. Brunson, MD MSMA President 2014-2015.

PMID- 25771625
TI  - JFC seeks good Samaritan doctors.

PMID- 25771626
TI  - Harper Grace's law: providing hope to suffering children and opportunity to the
      state.

PMID- 25771627
TI  - Dr. Scott Hambleton answers your questions.

PMID- 25771628
TI  - Eliminating the perverse incentive.

PMID- 25771629
TI  - Ultrasound-guided fine needle aspiration in the diagnosis of thyroid nodules.
AB  - A retrospective study of 28 patients who underwent ultrasound-guided fine needle
      aspiration (FNA) biopsy for thyroid nodular disease was performed to assess the
      diagnostic accuracy of ultrasound-guided FNA biopsy in detecting malignancy of
      the thyroid. Sensitivity, specificity, positive predictive value, and negative
      predicative value were evaluated with respect to final histological surgical
      pathology. The study's results substantiate those of previous studies: when there
      is a negative ultrasound-guided FNA, there is high probability that the patient
      is free of thyroid malignancy and may be followed clinically without the need for
      surgery.

PMID- 25771630
TI  - Denial of scans.

PMID- 25771631
TI  - About long-term oxygen therapy.

PMID- 25771633
TI  - Adding value to membership.

PMID- 25771632
TI  - Inaugural address of the 147th President Claude D. Brunson, MD.

PMID- 25771634
TI  - Untruths about immunizations.

PMID- 25771635
TI  - Professional rasslin'.

PMID- 25771636
TI  - Playing the part.

PMID- 25771637
TI  - 9 signs of a satisfied physician.

PMID- 25771638
TI  - Beyond the clinic.

PMID- 25771639
TI  - The physician assistant will see you now.

PMID- 25771640
TI  - Ski enthusiast.

PMID- 25771641
TI  - Noteworthy addition.

PMID- 25771642
TI  - NEW jobs for new times: physicians assume roles that reflect changes in health
      care.

PMID- 25771643
TI  - Common bond. On the limitations of a shared faith.

PMID- 25771644
TI  - Physicians prevail on Avera Marshall autonomy case.

PMID- 25771645
TI  - A victory for physicians and patients.

PMID- 25771646
TI  - Let's talk to our patients about hospice. Too many who could benefit from it are
      learning about the option too late. .

PMID- 25771647
TI  - Minnesota's new APRN law. What it means for physicians and their practices.

PMID- 25771648
TI  - Telemedicine for postoperative visits at the Minneapolis VA Medical Center.
      Results of a needs assessment study.
AB  - The Minneapolis VA Medical Center initiated a telemedicine program in the early
      1990s as a way to streamline care and increase convenience for patients and
      clinicians. In this study, we explored employing telemedicine for postoperative
      visits for patients in the general surgery clinic. We surveyed 346 veterans about
      their preferred method of follow-up. In addition, we asked about their need to
      complete insurance paperwork, use of VA satellite clinics, distance from the VA
      Medical Center and from the nearest satellite clinic, and need for travel
      assistance. We found half of the respondents preferred face-to-face follow-up
      while the other half preferred follow up using some form of telemedicine. These
      findings suggest there is a demand for remote postop visits using telemedicine
      and that such visits may have advantages over face-to-face clinic appointments,
      especially for patients who have to travel long distances. Further studies are
      ongoing to determine the actual acceptance of remote visits by the patients and
      surgeons and to determine if there have been delays in recognition of
      postoperative complications.

PMID- 25771649
TI  - The role of the generalist in the initial treatment of adolescent anorexia
      nervosa. .
AB  - Anorexia nervosa is a potentially serious illness characterized by the sufferer
      having a malignant fear of gaining weight and being fat. It was believed to stem
      from psychosocial problems. Treatment of the adolescent with anorexia has
      typically involved an inpatient stay in a specialized center where he or she can
      receive therapy aimed at changing thinking and exploring family dynamics. A newer
      strategy, family-based treatment, focuses on the young person's physical state.
      It can be initiated by a primary care physician during an outpatient visit. This
      article introduces this new paradigm for treating anorexia nervosa in adolescents
      and outlines the role of the primary care physician in diagnosing, treating and
      supporting the patient.

PMID- 25771650
TI  - Use of implant-supported prostheses in edentulous mandibles among prosthodontists
      in Sweden.
AB  - The aim of this study was to investigate the production of mandibular implant
      supported fixed and removable prostheses among prosthodontic specialists in
      Sweden and to compare the results with findings in a similar study made in 2001
      (17). Questionnaires regarding treatment with mandibular implant prostheses
      during 20011 were mailed to all specialists in prosthodontics in Sweden (n = 156,
      according to available data). Of the 156 questionnaires, 129 (83%) were returned
      and of those 114 were completed. The reported number of treatments with
      mandibular implant-supported prostheses varied much among the specialists. Fixed
      implant prostheses were more common than overdentures (means 11 and 3, median
      values 8 and 2, respectively). However, the range was large for both
      alternatives. Ten (9%) of the specialists reported no treatment with fixed
      implant prostheses while 29 (25%) had not made any implant overdenture during
      2011. The most common anchorage system for overdentures in 2011 (as well as in
      2001) was two un-splinted implants with ball attachments or Locator abutments.
      The most common reasons for choosing overdenture treatment instead of a fixed
      implant prosthesis in 2011 were the reduced cost and the patient's main wish to
      improve denture retention. A majority of the prosthodontists (58%) reported that
      patients with implant overdentures were as satisfied as those with fixed implant
      supported prostheses, whereas 40% claimed they were less satisfied. Two
      respondents (2%) considered that overdenture patients were more satisfied than
      those with a fixed prosthesis. It can be concluded that the general attitude
      among Swedish prosthodontists towards implant overdentures has not changed much
      during the 10-year period between the present and the previous investigation.An
      overdenture is still a seldom-used option in implant treatment of patients with
      edentulous mandibles in Sweden. Instead, a fixed implant-supported prosthesis
      continues to be the preferred option,

PMID- 25771651
TI  - Oral health-related quality of life and its relationship to self-reported oral
      discomfort and clinical status.
AB  - The impact of oral health on quality of life is one aspect when it comes to
      understanding the significance of oral health. The aim of this study was to
      analyse the self-reported oral discomfort and clinical status of individuals
      reporting oral problems never/very seldom affecting quality of life during the
      last year and compare them with individuals who reported oral problems hardly
      ever/occasionally or often/very often during the the same period. The study
      comprised a stratified random sample of 515 individuals who lived in four
      parishes in the City of Jonkoping, Sweden, and turned 20, 30, 40, 50, 60, 70 and
      80 years of age in 2003. The impact of oral health on quality of life was
      examined using the OHIP-14 questionnaire. The individuals were also examined
      clinically and radiographically. Of the participants, 21% reported no experience
      of impaired quality of life and 20% of the individuals reported that they had
      experienced impaired quality of life often or very often during the last year.
      The highest frequency of oral problems was found among individuals aged 20 and 80
      years. Subjective symptoms, such as grinding/clenching and headache, were found
      among 20- and 30-year-olds. Edentulous individuals and individuals with many
      missing teeth, individuals with severe periodontal disease or subjective dry
      mouth answered that they experienced problems according to the OHIP-14 often or
      very often. A number of individuals, young and old, had thus experienced
      subjective or clinically verified oral conditions associated with a negative
      experience of quality of life. This complementary information will provide a
      deeper understanding of the importance of oral health in the population.

PMID- 25771652
TI  - Detectability of normal anatomy in digital panoramic radiographs.
AB  - The aim of this study was to evaluate the image quality of digital panoramic
      radiographs and its correlation with the detectability of normal anatomical
      structures. The effects of image enhancement on the detectability were also
      studied. A total of 500 panoramic images (DICOM format) obtained with a storage
      phosphor-based digital system were evaluated. The image quality and the
      detectability of selected normal anatomical structures were evaluated in all
      images. Images with inadequate image quality were subjected to enhancement after
      which the detectability of the structures was re-evaluated. Only 9% of the images
      were classified as having adequate technical quality. The main sources of poor
      image quality were that the patient's tongue was not held against the palate and
      incorrect positioning of the patient. Not holding the tongue against the palate
      was found to have a negative impact on the detectability of maxillary structures.
      Of the images with horizontal positioning errors the patient's head was rotated
      to the left in 81% (70 images). The most effective form of enhancement was a
      combination of increased contrast and decreased brightness. Images in which the
      tongue was not held against the palate were partially improved, whereas images
      with positioning errors remained unaffected by this enhancement. In conclusion,
      most of the panoramic images showed some technical flaws. The marginal bone level
      and the maxillary area were the most difficult areas to reproduce. Retakes could
      be avoided in some cases by using image enhancement. However, this should not be
      regarded as an option to avoid poor image quality.

PMID- 25771653
TI  - New policies and practices suggested for avoiding RSIs.

PMID- 25771654
TI  - EASE app updates families on patients' progress during surgery.

PMID- 25771655
TI  - Reducing emergency surgical procedures could save $1 billion.

PMID- 25771657
TI  - Top 10 health technology hazards for 2015 are named.

PMID- 25771656
TI  - New curriculum aims to reduce hazards of energy devices in the OR.

PMID- 25771658
TI  - Wise use of social media can enhance your professional career.

PMID- 25771659
TI  - Surgeon sees standardization and data as keys to higher value healthcare.

PMID- 25771660
TI  - Achieving anesthesia provider accountability will boost OR performance.

PMID- 25771661
TI  - Professional standards and patient empathy ease burden of payment collection.

PMID- 25771662
TI  - [Toxicology in small animal clinical medicine].

PMID- 25771663
TI  - [Poisoning cases in livestock].

PMID- 25771664
TI  - [Current understanding of differential sensitivity of animals to toxic
      substances: species, strain and individual differences].

PMID- 25771665
TI  - [Pediatric exposure to liquid detergent capsules in Japan].

PMID- 25771666
TI  - [Complex regional pain syndrome in a patient with acute drug poisoning: a case
      report].
AB  - We report a case with transition to complex regional pain syndrome (CRPS) caused
      by nerve injury associated with crush syndrome. The diagnosis was delayed because
      of coma due to acute drug poisoning. A 44-year-old man had attempted suicide by
      taking massive amounts of psychotropic drugs 2 days earlier and was transported
      to our hospital by ambulance. His arms had been compressed due to the prolonged
      (2 days) consciousness disturbance, and he experienced non-traumatic crush
      syndrome and rhabdomyolysis. Acute renal failure was prevented with massive
      infusion and hemofiltration. However, he experienced muscle and nerve injury at
      the compressed area, which presumably led to CRPS. In cases of suspected crush
      syndrome associated with acute drug poisoning, it is also important to recognize
      the possibility of developing CRPS.

PMID- 25771667
TI  - Benzalkonium chloride intoxication caused by intravenous self-injection.
AB  - BACKGROUND: Benzalkonium chloride (BZK) is widely used as a germicide in
      hospitals and other places. Although several cases of accidental oral intake of
      BZK have been reported, there have been few reported cases of BZK toxicity due to
      intravenous injection. CASE REPORT: A male nurse in his 40 s injected 15 mL of
      10% BZK (Osvan S) directly into his left antebrachial vein while at home, as a
      suicide attempt. The patient was admitted to our hospital 1 hour later. Acute
      respiratory distress syndrome (ARDS) was diagnosed by blood gas analysis, chest X
      ray, and CT scan. Due to extracorporeal blood purification therapy, including
      hemoperfusion and plasma exchange, serum BZK became undetectable. However, the
      ARDS was not improved. Extracorporeal blood purification therapy consisting of
      continuous hemodiafiltration (CHDF) was continued to treat the ARDS. After
      performing CHDF for the next 36 hours, improvement of both the PaO2/FiO2 ratio
      and chest X-ray findings was noted. Tracheal extubation was performed on day 9
      and no further complications occurred after this period, he was discharged on day
      21. CONCLUSION: Extracorporeal blood purification therapy is probably effective
      for treatment of BZK intoxication by intravenous injection.

PMID- 25771668
TI  - [Case of law-evading herbs poisoning that induced shock and myocardial damage].
AB  - Law-evading herbs may induce poisoning symptoms, especially when they contain
      synthetic cannabinoids. However, their detailed pharmacological effects have not
      yet been clarified. Some reports have previously described symptoms of poisoning,
      but only a few reports have so far described shock and myocardial damage (MD). We
      experienced a case of shock and MD in a patient who had smoked law-evading herbs.
      A 61-year-old male presented at an emergency department 8 hours after smoking law
      evading herbs (Rush Trip, High Men Monster) with chest pain. A vasopressor agent
      was administered to treat shock and antiarrhythmic drugs were administered due to
      ventricular arrhythmia. The contents of the law-evading herbs were unknown, so an
      in-hospital follow-up was conducted to treat the patient's symptoms. The follow
      up blood test showed an increased level of cardiac enzymes, which thereafter
      demonstrated a spontaneous remission. The systemic conditions tended to improve
      and the patient was discharged from the hospital on the 5th hospital day. The
      contents of the law-evading herbs in question were thereafter,analyzed, and
      synthetic cannabinoids (JWH-210, JWH-081 and JWH-122) as well as caffeine were
      detected. The cause for the poisoning symptoms were suspected to be the presence
      of synthetic cannabinoids and caffeine. Such law-evading herbs may contain
      synthetic cannabinoids and caffeine which both may induce shock and MD.

PMID- 25771669
TI  - [BIS values were useful on the evaluation of consciousness recovery in acute
      Vegetamin-A poisoning: report of a case].
AB  - A 37-year-old man was admitted to our hospital with acute phenobarbital
      poisoning. On arrival, he was in deep coma with respiro-circulatory depressions.
      The serum concentration of the agent was elevated to 149.04 MUg/mL which was
      consistent with a lethal concentration level. He underwent a gastric lavage,
      administration of activated charcoal, urinary alkalinazation and bowel
      irrigation. Respiro-circulatory status was recovered rapidly, while the serum
      concentration of phenobarbital did not decrease smoothly. Although the
      concentration of the agent decreased to 77.07 MUg/mL that should be a comatose
      level, BIS values were gradually elevated, and then eventually the patient
      regained his consciousness. Because he was a chronic user of Vegetamin-A
      containing phenobarbital, the serum level might not have been correlated with
      symptoms. BIS values were highly reflective of the consciousness level, so it
      could be a useful indicator for predicting the consciousness levels of patients
      in deep coma with acute poisoning from hypnotic agents.

PMID- 25771670
TI  - [Case of continuous trans-arterial calcium gluconate infusion using a direct
      arterial sphygmomanometry line that exhibited dramatic improvement of chemical
      burns on the fingers caused by hydrofluoric acid].
AB  - Hydrofluoric acid (HFA) is commonly used and many injuries occur on the upper
      extremities following exposure to HFA. The use of calcium gluconate (CG) 
      containing gel or local injections of CG are widely used for the initial
      treatment of HFA exposure. However, severe pain continues in some cases despite
      the treatment. There was a report that trans-arterial CG infusion could improve
      HFA burns, however, such treatment is not an established clinical procedure. A 30
      year-old male presented at our hospital with severe pain in his left thumb. He
      had been cleaning tiles with an HFA-containing detergent. We diagnosed him with a
      chemical burn due to HFA exposure. Local CG injections were tried several times,
      but his terrible pain continued. Therefore, a direct arterial sphygmomanometry
      line was inserted from the left radial artery, and continuous transarterial CG
      injection was performed. His terrible pain dramatically improved. Direct arterial
      sphygmomanometry systems are widely used in the critical care field to monitor
      the hemodynamics and ICU staffs are used to dealing with it. Moreover, continuous
      saline infusion prevents the tube obstruction. Continuous CG infusion from a
      direct arterial sphygmomanometry line is simple and safe way to administer CG in
      HFA burns.

PMID- 25771671
TI  - [Acute renal failure and hearing loss due to sodium bromate intoxication].

PMID- 25771672
TI  - [Sources of information about poisoning].

PMID- 25771673
TI  - [Introduction to the series of Topics from the Joint JSCT-JSOT symposia].

PMID- 25771674
TI  - [Topics in the percellome toxicogenomics project].

PMID- 25771675
TI  - [Investigation of acute poisoning in dogs based on JPIC inquiries].

PMID- 25771676
TI  - [A field study of tundra plant litter decomposition rate via mass loss and carbon
      dioxide emission: the role of biotic and abiotic controls, biotope, season of
      year, and spatial-temporal scale].
AB  - Although many recently published original papers and reviews deal with plant
      matter decomposition rates and their controls, we are still very short in
      understanding of these processes in boreal and high latiude plant communities,
      especially in permafrost areas of our planet. First and foremost, this is holds
      true for winter period. Here, we present the results of 2-year field observations
      in south taiga and south shrub tundra ecosystems in European Russia. We pioneered
      in simultaneous application of two independent methods: classic mass loss
      estimation by litter-bag technique, and direct measurement of CO2 emission
      (respiration) of the same litter bags with different types of dead plant matter.
      Such an approach let us to reconstruct intra-seasonal dynamics of decomposition
      rates of the main tundra litter fractions with high temporal resolution, to
      estimate the partial role of different seasons and defragmentation in the process
      of plant matter decomposition, and to determine its factors under different
      temporal scale.

PMID- 25771677
TI  - [A formal description of mammals' behavior based on data on snow tracking, with
      pine marten (Martes martes) as a case study].
AB  - The formalism allowing to describe animals' behavior is based on the model of
      informational interactions between an animal and its environment. The model may
      be represented as an assemblage consisting of two blocks. The first block, which
      corresponds to the perception system, is a probabilistic operator: it selects an
      object of certain class out of many objects randomly encountered by an animal
      while it moves around. The selected object keeps its actuality as an input symbol
      for the second block of the assemblage during one or several cycles of the block
      operation. The second block, being afinite structural probabilistic automaton,
      generates output reactions to the input symbol. The structural automaton, which
      consists of elementary automata, produces a sequence of output reactions in
      course of interactions with the selected object: After exhaustion of the previous
      input actuality, the assemblage moves to the next cycle. At that, the
      probabilistic operator comes back to the receptive state and produces next
      output. Automaton "inputs" correspond to objects of certain classes, selectively
      perceived by an animal; "outputs" correspond to a sequence of elementary motor
      reactions. Based on data on snow tracking of pine marten foraging activity, there
      have been composed: the assemblage input and output alphabets, a conjugation
      matrix of input signals and internal states of the first elementary automaton
      that is contained in the second block structure, and transition probability
      matrices for the states of the second block elementary automata, which are
      defined for a class of environmental objects when foraging activity occurs. The
      proposed formalism makes it possible to convert field data on tracking into the
      unified form, detect key circumstances of animals' behavioral activity, and
      analyze this natural phenomenon in detail.

PMID- 25771678
TI  - [Advantages and limitations of interspecies associations in northern migratory
      sandpipers (Charadrii, Aves)].
AB  - Investigations were carried out at two stations of Ornithological Unit, IBPN FEB
      RAS, located in Nizhnekolymsk District, Yakutia, starting from May 15-20 in 1984,
      1985, 1987, 1988, and 1990; at the northern coast of Pukhovoy Bay, Southern
      Island of Novaya Zemlya starting from June 1 in 1994; at Cape Beliy Nos, the
      Yugorsky Peninsula, starting from June 1 in 1995-1997. Classic associations are
      detected in interspecies flocks of sandpipers between the following species: the
      Pacific golden plover and the curlew sandpiper, the pectoral sandpiper and the
      long-billed dowitcher, the pectoral sandpiper and the dunlin, the grey plover and
      the dunlin. However, total amount of birds that form associations is not large.
      In species of group "A" (the grey plover, the Pacific golden plover, the pectoral
      sandpiper), no difference has been observed in migratory birds behavior within
      inter- or conspecific flocks. Species of group "B" (the dunlin, the curlew
      sandpiper, the long-billed dowitcher), on the contrary, change their behavior
      sharply depending on whether they belong to an association or not. Species of
      group "A" do not get any advantages when forming an association. Unlike them,
      species of group "B" profit from associating: a part of time spent in foraging
      substantially increases; more time is spent on rest and less time is spent on
      reconnaissance and vigilance (readiness for actions); safety of birds is
      enhanced. On the other hand, in species of group "B" there are also disadvantages
      related with associating: i.e., interspecies competition for food; foraging in
      suboptimal habitats which, in turn, may lead to notable increase of time spent by
      birds in foraging. An assumption is put forward that in species of group "B"
      advantages and limitations of associating cancel each other to a certain extent,
      and this explains rather small number of birds forming associations.

PMID- 25771679
TI  - [Aerosol deposition in nasal passages of burrowing and ground rodents when
      breathing dust-laden air].
AB  - In subterranean rodents, which dig down the passages with frontal teeth,
      adaptation to the underground mode of life presumes forming of mechanisms that
      provide protection against inhaling dust particles of different size when
      digging. One of such mechanisms can be specific pattern of air flow organization
      in the nasal cavity. To test this assumption, comparative study of geometry and
      aerodynamics of nasal passages has been conducted with regard to typical
      representative of subterranean rodents, the mole vole, and a representative of
      ground rodents, the house mouse. Numerical modeling of air flows and deposition
      of micro- and nanoparticle aerosols indicates that sedimentation of model
      particles over the whole surface of nasal cavity is higher in mole vole than in
      house mouse. On the contrary, particles deposition on the surface of olfactory
      epithelium turns out to be substantially less in the burrowing rodent as compared
      to the ground one. Adaptive significance of the latter observation has been
      substantiated by experimental study on the uptake ofnanoparticles of hydrated
      manganese oxide MnO x (H2O)x and Mn ions from nasal cavity into brain. It has
      been shown with use of magnetic resonance tomography method that there is no
      difference between studied species with respect to intake of particles or ions by
      olfactory bulb when they are introduced intranasally. Meanwhile, when inhaling
      nanoparticle aerosol of MnCl2, deposition of Mn in mouse's olfactory bulbs
      surpasses markedly that in vole's bulbs. Thereby, the morphology of nasal
      passages as a factor determining the aerodynamics of upper respiratory tract
      ensures for burrowing rodents more efficient protection of both lungs and brain
      against inhaled aerosols than for ground ones.

PMID- 25771680
TI  - [Competitive intransitivity among species in biotic communities].
AB  - Contemporary state of the competitive intransitivity hypothesis is considered.
      Intransitive competition among species occurs when, for example, species A
      outcompetes species B, B outcompetes C, and C out-competes A (sometimes written
      as A > B > C > A). In the first part of the article, a summary of the studies of
      competitive intransitivity is given. Examples of really existing intransitive
      loops are discussed, as well as simulation models that provide a theoretical
      explanation for these processes. Pro hac vice, sufficient potential diversity of
      community, species interactions carried out in relatively stable limited space
      that can be reclaimed, and a penalty for the acquisition of competitive ability
      are prerequisite. In the second part, the hypothesis of competitive
      intransitivity is compared with neutral theory and niche theory. The results are
      believed to make some generalizations possible which could stimulate deeper
      understanding of the species coexistence phenomenon.

PMID- 25771681
TI  - [Picocyanobacteria in eutrophic reservoirs of the Middle Volga: abundance,
      production, viral infection].
AB  - During the summer season of 2010, abundance and productivity of picocyanobacteria
      in Gorky and Cheboksary Reservoirs have being examined. It is found out that in
      the eutrophic reservoirs of the Middle Volga abundance and biomass of
      picocyanobacteria, averaged over the water column, varied within the range of (34
      322) x 10(3) cells/ml and 38-455 mg/m3 respectively. In more productive
      Cheboksary Reservoir, the contribution of picocyanobacteria in total biomass and
      production of phytoplankton (4.7 +/- 0.7 and 8.3 +/- 1.3% respectively) was lower
      than in less productive Gorky Reservoir (10.6 +/- 2.1 and 19.2 +/- 3.0%
      respectively). In both reservoirs, high level of picocyanobacteria infection by
      viruses was detected. The frequency of visible infected cells and virus-induced
      mortality of picocyanobacteria in Cheboksary Reservoir were substantially higher
      (3.2 +/- 0.4% of total abundance and 21.8 +/- 2.9% of daily production) than in
      Gorky Reservoir (1.7 +/- 0.2% of total abundance and 11.0 +/- 1.7% of daily
      production). The results obtained indicate that in eutrophic reservoirs during
      summer bloom of large cyanobacteria their abundance is regulated to a great
      extent by viruses.

PMID- 25771683
TI  - Age-related characteristics of cutaneous melanoma in a Spanish Mediterranean
      population.
AB  - BACKGROUND: Melanoma is considered a heterogeneous tumor with genetic and
      environmental factors involved in its pathogenesis. The impact of these factors
      varies depending on age. OBJECTIVE: The aim of this study was to characterize the
      epidemiological, phenotypic, and histological features of patients with melanoma
      according to three age groups: <=40, 41-65, and >65 years. METHODS: A total of
      1122 consecutive patients with invasive melanoma definitively treated in our
      institution since January 2000 were selected from our melanoma database.
      Epidemiological, phenotypic, and histological data were retrieved and analyzed as
      a function of age. RESULTS: Female patients predominated in the younger age
      group. The location of cutaneous malignant melanoma differed with age. In the
      younger and middle age groups, tumors presented mainly on the trunk, while in the
      older group they were mainly found on the head/neck. Signs of actinic damage such
      as actinic keratoses, solar lentigines, or other skin tumors increased with age,
      while genetic factors such as family history of melanoma or a high number of
      common melanocytic nevi were more frequent in the younger group. CONCLUSION: Our
      results suggest that melanoma development in younger patients is the result of
      genetic factors, particularly related to multiple nevi, whereas in older patients
      environmental factors such as severe chronic sun exposure play a major role.

PMID- 25771682
TI  - Increased cerebral blood flow associated with better response inhibition in
      bipolar disorder.
AB  - Impairment on inhibitory tasks has been well documented in bipolar disorder (BD).
      Differences in cerebral blood flow (CBF) between BD patients and healthy
      comparison (HC) participants have also been reported. Few studies have examined
      the relationship between cognitive performance and regional CBF in this patient
      population. We hypothesized that group differences on an inhibitory task (the
      Delis-Kaplan Executive Function Scale's Color-Word Inhibition task) would be
      associated with differential CBF in bilateral anterior cingulate cortex (ACC),
      inferior parietal lobule (IPL) and dorsolateral prefrontal cortex (DLPFC)
      regions. Whole brain resting CBF was measured using Multiphase Pseudocontinuous
      Arterial Spin Labeling MR imaging for 28 euthymic BD and 36 HC participants.
      Total gray matter (GM) CBF was measured, and regional CBF values were extracted
      for each region of interest (ROI) using Freesurfer-based individual
      parcellations. Group, CBF, and group-by-CBF interaction were examined as
      predictors of inhibition performance. Groups did not differ in age, gender or
      education. BD patients performed significantly worse on Color-Word inhibition.
      There were no significant group differences in CBF in either total GM or in any
      ROI. There was a group by CBF interaction in the bilateral ACC, right IPL and
      right DLPFC such that better inhibitory performance was generally associated with
      higher resting state CBF in BD subjects, but not HC participants. Although CBF
      was not abnormal in this euthymic BD sample, results confirm previous reports of
      inter-episode inhibitory deficits and indicate that the perfusion-cognition
      relationship is different in BD compared to HC individuals.

PMID- 25771684
TI  - Structure of the WD40 domain of SCAP from fission yeast reveals the molecular
      basis for SREBP recognition.
AB  - The sterol regulatory element-binding protein (SREBP) and SREBP cleavage
      activating protein (SCAP) are central players in the SREBP pathway, which control
      the cellular lipid homeostasis. SCAP binds to SREBP through their carboxyl (C)
      domains and escorts SREBP from the endoplasmic reticulum to the Golgi upon sterol
      depletion. A conserved pathway, with the homologues of SREBP and SCAP being Sre1
      and Scp1, was identified in fission yeast Schizosaccharomyces pombe. Here we
      report the in vitro reconstitution of the complex between the C domains of Sre1
      and Scp1 as well as the crystal structure of the WD40 domain of Scp1 at 2.1 A
      resolution. The structure reveals an eight-bladed beta-propeller that exhibits
      several distinctive features from a canonical WD40 repeat domain. Structural and
      biochemical characterization led to the identification of two Scp1 elements that
      are involved in Sre1 recognition, an Arg/Lys-enriched surface patch on the top
      face of the WD40 propeller and a 30-residue C-terminal tail. The structural and
      biochemical findings were corroborated by in vivo examinations. These studies
      serve as a framework for the mechanistic understanding and further functional
      characterization of the SREBP and SCAP proteins in fission yeast and higher
      organisms. 

PMID- 25771685
TI  - Endophilin A1 regulates dendritic spine morphogenesis and stability through
      interaction with p140Cap.
AB  - Dendritic spines are actin-rich membrane protrusions that are the major sites of
      excitatory synaptic input in the mammalian brain, and their morphological
      plasticity provides structural basis for learning and memory. Here we report that
      endophilin A1, with a well-established role in clathrin-mediated synaptic vesicle
      endocytosis at the presynaptic terminal, also localizes to dendritic spines and
      is required for spine morphogenesis, synapse formation and synaptic function. We
      identify p140Cap, a regulator of cytoskeleton reorganization, as a downstream
      effector of endophilin A1 and demonstrate that disruption of their interaction
      impairs spine formation and maturation. Moreover, we demonstrate that knockdown
      of endophilin A1 or p140Cap impairs spine stabilization and synaptic function. We
      further show that endophilin A1 regulates the distribution of p140Cap and its
      downstream effector, the F-actin-binding protein cortactin as well as F-actin
      enrichment in dendritic spines. Together, these results reveal a novel function
      of postsynaptic endophilin A1 in spine morphogenesis, stabilization and synaptic
      function through the regulation of p140Cap. 

PMID- 25771686
TI  - Emotion regulation deficits in euthymic bipolar I versus bipolar II disorder: a
      functional and diffusion-tensor imaging study.
AB  - OBJECTIVES: Emotion regulation deficits are a core feature of bipolar disorder.
      However, their potential neurobiological underpinnings and existence beyond
      bipolar I disorder remain unexplored. Our main goal was to investigate whether
      both individuals with bipolar I and bipolar II disorder show deficits in emotion
      regulation during an attention control task, and to explore the
      neurophysiological underpinnings of this potential deficit. METHODS: Twenty
      healthy controls, 16 euthymic participants with bipolar I disorder, and 19
      euthymic participants with bipolar II disorder completed psychometric and
      clinical assessments, a neuroimaging emotion regulation paradigm, and an
      anatomical diffusion-weighted scan. Groups were matched for age, gender, and
      verbal IQ. RESULTS: During the presence of emotional distracters, subjects with
      bipolar I disorder showed slowed reaction times to targets, and increased blood
      oxygenation level-dependent (BOLD) responses in the amygdala, accumbens, and
      dorsolateral prefrontal cortex, but not increased inverse functional connectivity
      between these prefrontal and subcortical areas, and altered white matter
      microstructure organization in the right uncinate fasciculus. Subjects with
      bipolar II disorder showed no altered reaction times, increased BOLD responses in
      the same brain areas, increased inverse functional connectivity between the
      prefrontal cortex and amygdala, and no abnormalities in white matter
      organization. CONCLUSIONS: Participants with bipolar I disorder showed
      abnormalities in functional and anatomical connectivity between prefrontal
      cortices and subcortical structures in emotion regulation circuitry. However,
      these deficits did not extend to subjects with bipolar II disorder, suggesting
      fundamental differences in the pathophysiology of bipolar disorder subtypes.

PMID- 25771687
TI  - Is deep brain stimulation a treatment option for addiction?

PMID- 25771688
TI  - Guidance for reporting qualitative manuscripts.

PMID- 25771689
TI  - The concentration of the global alcohol industry and its penetration in the
      African region.
AB  - AIMS: To describe the penetration and expansion of the global alcohol industry
      into the African region, as a context for exploring the implications for public
      health. METHODS: Source materials for this study came primarily from market
      research and the business press. This was supplemented by industry sources (from
      websites, company annual reports), World Health Organization reports and the
      scientific literature. RESULTS: Drinking in Africa is characterized by high rates
      of abstention and a high prevalence of heavy episodic consumption among those who
      drink. Much of the region is currently experiencing a rapid rise in consumption.
      Rising populations and income and the rapid pace of urbanization make Africa very
      attractive to the global alcohol industry, and industry leaders have identified
      Africa as a key area for growth. The shift from collaboration to competition in
      Africa among the global alcohol companies has prompted increasing alcohol
      production, promotion, new product development, pricing schemes and stakeholder
      lobbying. CONCLUSIONS: Beer consumption has increased across most of the
      continent, and global brewers view themselves as legitimate players at the
      alcohol policy table. Weak alcohol policy environments may be compromised further
      in terms of public health protections by alcohol industry opposition to effective
      measures such as marketing regulations, availability controls and taxation.

PMID- 25771690
TI  - Commentary on Raitasalo et al. (2015): the great potential in nation-wide
      registers to study prescription drug use and abuse.

PMID- 25771691
TI  - Commentary on Burns et al. (2015): retention in buprenorphine treatment.

PMID- 25771692
TI  - Commentary on Dawkins et al. (2015): electronic cigarettes - from smoking
      cessation to smoking sensation and back.

PMID- 25771693
TI  - Rewarding smoking cessation in pregnancy-will women cheat to gain incentives?

PMID- 25771694
TI  - Continuing efforts to improve cessation outcomes with pregnant cigarette smokers.

PMID- 25771695
TI  - Is the recent ban on animal testing of legal high products a fatal blow to the
      development of a legal market for 'low-risk' psychoactive products in New
      Zealand?

PMID- 25771698
TI  - Mass spectrometric and enzymatic evidence confirm the existence of anthocyanidin
      3,5-O-diglucosides in cabernet sauvignon (Vitis vinifera L.) grape berries.
AB  - It has been widely accepted that anthocyanidin 3,5-O-diglucosides do not exist in
      Vitis vinifera L. Cabernet Sauvignon (CS) berries. However, our anthocyanin
      analyses using HPLC-ESI-MS/MS detected the existence of a low level of
      anthocyanidin 3,5-O-diglucosides in the Cabernet Sauvignon grape berries grown in
      China. The authenticity of these samples was confirmed with microsatellite
      markers. The existence of anthocyanidin 3,5-O-diglucoside was further verified by
      the enzymatic evidence for the first time. Four putative 5-O-glucosyltransferase
      (5GT) genes were isolated from the Cabernet Sauvignon berries. The enzymatic
      analysis showed that a recombinant protein (designated as Vv5GT3) glucosylated
      the 3-O- and 5-O-positions of anthocyanidins and flavonols. A phylogenetic
      analysis revealed that this bifunctional enzyme belongs to the 5GT subfamily of
      UDP-glycosyltransferases. This finding brought a new understanding of the
      anthocyanins' profile and their biosynthesis in V. vinifera and would be helpful
      for further investigations of the mechanism of accumulation of anthocyanidin
      diglucosides in Cabernet Sauvignon berries in China's wine-producing regions.

PMID- 25771699
TI  - A Bayesian model for the identification of differentially expressed genes in
      Daphnia magna exposed to munition pollutants.
AB  - In this article we propose a Bayesian hierarchical model for the identification
      of differentially expressed genes in Daphnia magna organisms exposed to chemical
      compounds, specifically munition pollutants in water. The model we propose
      constitutes one of the very first attempts at a rigorous modeling of the
      biological effects of water purification. We have data acquired from a
      purification system that comprises four consecutive purification stages, which we
      refer to as "ponds," of progressively more contaminated water. We model the
      expected expression of a gene in a pond as the sum of the mean of the same gene
      in the previous pond plus a gene-pond specific difference. We incorporate a
      variable selection mechanism for the identification of the differential
      expressions, with a prior distribution on the probability of a change that
      accounts for the available information on the concentration of chemical compounds
      present in the water. We carry out posterior inference via MCMC stochastic search
      techniques. In the application, we reduce the complexity of the data by grouping
      genes according to their functional characteristics, based on the KEGG pathway
      database. This also increases the biological interpretability of the results. Our
      model successfully identifies a number of pathways that show differential
      expression between consecutive purification stages. We also find that changes in
      the transcriptional response are more strongly associated to the presence of
      certain compounds, with the remaining contributing to a lesser extent. We discuss
      the sensitivity of these results to the model parameters that measure the
      influence of the prior information on the posterior inference. 

PMID- 25771700
TI  - Signs of RV overload on the athlete's ECG.
AB  - There is increasing evidence that regular intense endurance exercise can promote
      structural and electrical remodeling of the right ventricle (RV). These
      physiological changes can be profound and are frequently accompanied by ECG
      changes in the right precordial leads, thereby mimicking features observed in
      arrhythmogenic right ventricular cardiomyopathy (ARVC). Because the 12-lead ECG
      is used as both a screening and diagnostic tool for the detection of conditions
      associated with sudden death in athletes, it is of fundamental importance to have
      a good understanding of the ECG features that distinguish physiological
      adaptations to endurance exercise from those related to RV pathology as well as
      their potential overlap. This article describes ECG findings observed in healthy
      endurance athletes versus athletes with underlying RV pathology and illustrates
      their differentiation using 4 case presentations. 

PMID- 25771701
TI  - Ventricular couplets but not isolated extrasystoles induce a "female" sustained,
      supraventricular tachycardia. What is the mechanism?
AB  - This is the case of a 28-year-old woman with sustained supraventricular
      tachycardia induced only by monomorphic ventricular couplets but not by isolated
      extrasystoles. The careful examination of electrocardiogram (ECG) was able to
      identify the mechanism of the tachycardia in the absence of electrophysiologic
      investigation. The tachycardia resulted sustained and symptomatic only during
      periods. 

PMID- 25771702
TI  - Torsade de pointes in a patient with complete atrioventricular block and
      pacemaker failure, misdiagnosed with epilepsy.
AB  - A case of torsade de pointes (TdP) with complete atrioventricular block and
      pacemaker failure that was misdiagnosed as epilepsy is presented herein. An 82
      year-old female with recurrent seizure-like attacks showed epileptiform discharge
      during an electroencephalogram recording. A long QT interval and severe
      hypokalemia induced runs of TdP, which was related to pacemaker lead fracture,
      was detected during Holter recording and accompanied with episodes of seizures.
      After a DDD pacemaker with a new ventricular lead was replaced, there was no
      recurrence of any seizure-like attacks. Bradycardia-mediated TdP associated with
      complete atrioventricular block should not be missed in patients with recurrent
      seizure-like attacks even after pacemaker implantation.

PMID- 25771703
TI  - Early occipital injury affects numerosity counting but not simple arithmetic.
AB  - This study investigated the effects of early occipital injury on the development
      of counting and simple arithmetic abilities in an occipital epileptic patient.
      This patient had obvious softening lesions in the bilateral occipital regions due
      to viral encephalitis at the age of 1.5 years. Results showed that she could
      perform subitizing and simple arithmetic very well, but could not perform
      numerosity counting tasks. These results suggest that the occipital cortex plays
      an important role in the development of numerosity counting skills, but not in
      the development of subitizing and simple arithmetic. 

PMID- 25771704
TI  - Aberrant expression and dysfunction of TLR2 and its soluble form in chronic HBV
      infection and its regulation by antiviral therapy.
AB  - Toll-like receptor 2 (TLR2) plays an important role in the immunopathogenesis of
      hepatitis B virus (HBV) infection. The relationship between TLR2 expression and
      clinical outcome of chronic HBV infection is not yet elucidated in details so
      far. Here, we employed clinical cohorts to investigate TLR2 expression and
      function in different phases of HBV infection and dynamic changes of TLR2
      expression in HBeAg-positive chronic hepatitis B (CHB) patients during antiviral
      therapy. TLR2 was mainly expressed in monocytes and its ligand stimulation
      resulted in TNF-alpha, IL-6 and IL-10 production. Serum soluble TLR2 (sTLR2)
      levels were negatively correlated with TLR2 mRNA in PBMCs. As compared with
      immunotolerant carriers and inactive carriers, CHB patients showed an elevated
      TLR2 expression and TNF-alpha, IL-6 induction in PBMC, but had a decreased level
      of sTLR2 in serum. However, TLR2 expression and TNF-alpha induction in monocytes
      of CHB patients remained lower than healthy controls. Furthermore, higher TLR2
      expression in PBMCs and lower level of sTLR2 in serum at baseline were predictive
      of a complete response to 52 weeks of telbivudine (LdT) therapy. Temporal dynamic
      analysis showed that TLR2 expression was restored with viral suppression and ALT
      normalization from week 12 to 24. However, peg-IFN-alpha-2a therapy induced a
      slightly decline in TLR2 expression. In conclusion, TLR2 expression and function
      in monocytes were impaired by chronic HBV infection. Higher TLR2 expression in
      PBMC and lower level of sTLR2 in serum at baseline were associated with a
      complete response to LdT therapy, and dynamic TLR2 expression was differently
      regulated by LdT and peg-IFN-alpha-2a therapy.

PMID- 25771705
TI  - Tetranychus urticae-triggered responses promote genotype-dependent conspecific
      repellence or attractiveness in citrus.
AB  - The citrus rootstocks sour orange and Cleopatra mandarin display differential
      resistance against Tetranychus urticae. Sour orange plants support reduced
      oviposition, growth rates and damage compared with Cleopatra mandarin plants.
      Jasmonic acid signalling and flavonoid accumulation have been revealed as key
      mechanisms for the enhanced resistance of sour orange plants. In this study, we
      observed that the release of T. urticae herbivore-induced plant volatiles (HIPVs)
      from sour orange plants has a marked repellent effect on conspecific mites
      associated with the production of the terpenes alpha-ocimene, alpha-farnesene,
      pinene and d-limonene, and the green leaf volatile 4-hydroxy-4-methyl-2
      pentanone. By contrast, T. urticae HIPVs from Cleopatra mandarin plants promote
      conspecific mite attraction associated with an increase in (2-butoxyethoxy)
      ethanol, benzaldehyde and methyl salicylate levels. HIPVs released from sour
      orange plants following T. urticae infestation induce resistance in Cleopatra
      mandarin plants, thereby reducing oviposition rates and stimulating the oxylipin
      biosynthetic gene lipoxygenase2 (LOX2). Cleopatra HIPVs do not affect the
      response to T. urticae of these rootstocks. We conclude that sour orange plants
      promote herbivore-induced resistance in Cleopatra mandarin plants and, despite
      the weak basal resistance of these rootstocks, herbivore resistance can be
      induced through the combination of HIPVs, such as alpha-ocimene and d-limonene.

PMID- 25771706
TI  - [Vitamin D and calcium in the prevention of falls].

PMID- 25771707
TI  - Factors that influence sunscreen application thickness and potential preservative
      exposure.
AB  - BACKGROUND/PURPOSE: Studies have shown that individuals apply less than the 2
      mg/cm(2) lotion sunscreen needed to achieve the labeled SPF. However, there is
      little information regarding the application of spray and stick sunscreens. The
      objectives of this study were to measure the amount of sunscreen applied to skin
      by different application methods, to examine the relationship between application
      and demographic factors, and to evaluate the potential for sensitization from the
      preservative methylisothiazolinone (MI) in lotion sunscreens. METHODS: Fifty-two
      participants applied lotion, spray, and stick sunscreen and answered a
      questionnaire. Lotion sunscreens were tested for MI content, and a margin of
      safety for the induction of skin sensitization was calculated. RESULTS: The
      geometric means for the application thickness of lotion, spray, and stick
      sunscreens were 1.1, 1.6, and 0.35 mg/cm(2), respectively. Several factors
      influenced sunscreen application thickness, including age and skin type. The MI
      concentration in tested sunscreen lotions ranged from <1 to 5.6 ppm, and likely
      MI exposures were below the threshold for induction of allergy (margin of safety
      > 8.1). CONCLUSIONS: In this study, sunscreen users applied different amounts of
      sunscreen depending on the application method, affording different levels of sun
      protection. Typical use of the sunscreens is not likely to result in MI
      sensitization.

PMID- 25771708
TI  - Study of the Behaviors of Gunshot Residues from Spent Cartridges by Headspace
      Solid-Phase Microextraction-Gas Chromatographic Techniques.
AB  - Gunshot residues, produced after shooting activity, have acquired their
      importance in analysis due to the notoriety of firearms-related crimes. In this
      study, solid-phase microextraction was performed to extract the headspace
      composition of spent cartridges using 85-MUm polyacrylate fiber at 66 degrees C
      for 21 min. Organic compounds, that is, naphthalene, 2,6-dinitrotoluene, 2,4
      dinitrotoluene, diphenylamine, and dibutyl phthalate were detected and analyzed
      by gas chromatography-flame ionization detection technique. Evaluation of
      chromatograms for diphenylamine, dibutyl phthalate, and naphthalene indicates the
      period after a gunshot was discharged, whether it was 1 days, 2-4 days, <5 days,
      10 days, 20 days, or more than 30 days ago. This study revealed the potential
      effects of environmental factors such as occasional wind blow and direct sunlight
      on the estimation of time after spent cartridges were discharged. In conclusion,
      we proposed reliable alternative in analyzing the headspace composition of spent
      cartridges in a simulated crime scene. 

PMID- 25771709
TI  - Medically unnecessary advanced diagnostic imaging and shared decision-making in
      the emergency department: opportunities for future research.

PMID- 25771710
TI  - Spatial memory in nonhuman primates implanted with the subdural pharmacotherapy
      device.
AB  - This study investigated the possible influence of the Subdural Pharmacotherapy
      Device (SPD) on spatial memory in 3 adult, male bonnet macaques (Macaca radiata).
      The device was implanted in and above the subdural/subarachnoid space and cranium
      overlaying the right parietal/frontal cortex: a circuitry involved in spatial
      memory processing. A large test chamber, equipped with four baited and four non
      baited food-ports at different locations, was used: reaches into empty food ports
      were counted as spatial memory errors. In this study of within-subject design,
      before SPD implantation (control) the animals made mean 373.3 +/- 114.9 (mean +/-
      SEM) errors in the first spatial memory test session. This value dropped to 47.7
      +/- 18.4 by the 8th session. After SPD implantation and alternating cycles of
      transmeningeal saline delivery and local cerebrospinal fluid (CSF) drainage in
      the implanted cortex the spatial memory error count, with the same port
      locations, was 33.0 +/- 12.2 during the first spatial memory test session,
      further decreasing to 5.7 +/- 3.5 by the 8th post-implantation session (P<0.001
      for trend). Replacing transmeningeal saline delivery with similar delivery of the
      GABAA receptor agonist muscimol (1.0mM) by the SPD did not affect the animals'
      spatial memory performance, which in fact included at least one completely error
      free session per animal over time. The study showed that complication-free
      implantation and use of the SPD over the parietal and frontal cortices for months
      leave spatial memory processes intact in nonhuman primates.

PMID- 25771711
TI  - Alterations of reward mechanisms in bulbectomised rats.
AB  - The positive association between alcoholism and depression is a common clinical
      observation. We investigated the relationship between depression and reward
      mechanisms using a validated animal model for depressive-like behaviour, the
      olfactory bulbectomy in rats. The effects of bilateral olfactory bulbectomy on
      reward mechanisms were studied in two different experimental paradigms - the
      voluntary self-administration of ethanol and the conditioned place preference to
      alcohol injection and compared to the effects of ethanol on locomotor activity
      and body core temperature. The voluntary ethanol intake was increased
      significantly in bulbectomised rats in a drinking experiment and also after a
      period of abstinence. Conditioned place preference (CPP) was induced in all
      animals. However, bulbectomised rats needed a higher dose of alcohol to produce
      CPP. The sedative effect of ethanol on locomotor activity was reduced in
      bulbectomised animals. Measurement of body temperature revealed a dose-dependent
      hypothermic effect of ethanol in both groups. These results suggest that the
      reward mechanisms may be altered in this animal model as a common phenomenon
      associated with depression. Furthermore, they support the hypothesis that the
      addictive and/or rewarding properties of some drugs of abuse may be modified in
      depression. 

PMID- 25771712
TI  - Neural representation of swallowing is retained with age. A functional
      neuroimaging study validated by classical and Bayesian inference.
AB  - We investigated the neural representation of swallowing in two age groups for a
      total of 51 healthy participants (seniors: average age 64 years; young adults:
      average age 24 years) using high spatial resolution functional magnetic resonance
      imaging (fMRI). Two statistical comparisons (classical and Bayesian inference)
      revealed no significant differences between subject groups, apart from higher
      cortical activation for the seniors in the frontal pole 1 of Brodmann's Area 10
      using Bayesian inference. Seniors vs. young participants showed longer reaction
      times and higher skin conductance response (SCR) during swallowing. We found a
      positive association of SCR and fMRI-activation only among seniors in areas
      processing sensorimotor performance, arousal and emotional perception. The
      results indicate that the highly automated swallowing network retains its
      functionality with age. However, seniors with higher SCR during swallowing appear
      to also engage areas involved in attention control and emotional regulation,
      possibly suggesting increased attention and emotional demands during task
      performance. 

PMID- 25771713
TI  - Cost-effectiveness of Sativex in multiple sclerosis spasticity: new data and
      application to Italy.
AB  - Multiple sclerosis (MS) is a chronic progressive disease that carries a high
      socioeconomic burden. Spasticity (rigidity and spasms) is common in MS and
      contributes to MS-related disability. This study aims to evaluate the cost
      effectiveness of Sativex((r)) (9-delta-tetrahydrocannabinol plus cannabidiol
      oromucosal spray) when used as add-on therapy for management of resistant MS
      related spasticity in the context of the Italian healthcare system. A previously
      published Markov model-based analysis for the German and Spanish context was
      replicated, adapting it to the Italian setting. Model parameters were updated to
      reflect recent findings about MS-related spasticity and use of Sativex in daily
      clinical practice. The base case incremental cost-effectiveness ratio for Sativex
      use in Italy over a 5-year period was estimated to be ?4968 per quality-adjusted
      life-year gained (year of costing: 2013). Sativex remained an efficient option in
      the Italian healthcare context - below the commonly accepted incremental
      threshold of ?30,000 per quality-adjusted life-year gained - when deterministic
      and probabilistic sensitivity analyses were conducted. Sativex can be regarded as
      a cost-effective treatment option for patients with MS-related spasticity in
      Italy. 

PMID- 25771714
TI  - Short- and long-term efficacy and mechanism of action of tumescent suction
      curettage for axillary hyperhidrosis.
AB  - BACKGROUND: Axillary hyperhidrosis is a common and distressing problem
      interfering with the life of affected individuals. Currently, local surgery is
      the treatment of choice once conservative treatment has failed. OBJECTIVES: To
      evaluate the clinical efficacy and safety of tumescent suction curettage (TSC) in
      treating axillary hyperhidrosis and to correlate it with histological markers.
      METHODS: Thirty patients (17 females and 13 males, average age 29.9 years)
      underwent TSC. After tumescent anaesthesia, a suction cannula was inserted in the
      axilla on each side through two tiny incisions and subcutaneous tissue was
      removed by suction. We evaluated the clinical efficacy and complications, and in
      a subset of patients performed biopsies before surgery, as well as 1 month and 1
      year after the operation. RESULTS: In comparison with preoperative values, the
      sweat rate was diminished by 85% after 1 month, 71% after 6 months, 77% after 12
      months and 61% after 24 months. The reduced efficacy with time was histologically
      correlated with an increase in the innervation, whereas the number of sweat
      glands continued to diminish. The majority of patients were satisfied with the
      operation but the satisfaction diminished with time. Patients with the highest
      preoperative sweat rates were the most satisfied after the intervention.
      CONCLUSION: TSC is an effective and safe treatment for axillary hyperhidrosis.
      The long-term recurrence may be due to reinnervation.

PMID- 25771715
TI  - Design and synthesis of target-responsive aptamer-cross-linked hydrogel for
      visual quantitative detection of ochratoxin A.
AB  - A target-responsive aptamer-cross-linked hydrogel was designed and synthesized
      for portable and visual quantitative detection of the toxin Ochratoxin A (OTA),
      which occurs in food and beverages. The hydrogel network forms by hybridization
      between one designed DNA strand containing the OTA aptamer and two complementary
      DNA strands grafting on linear polyacrylamide chains. Upon the introduction of
      OTA, the aptamer binds with OTA, leading to the dissociation of the hydrogel,
      followed by release of the preloaded gold nanoparticles (AuNPs), which can be
      observed by the naked eye. To enable sensitive visual and quantitative detection,
      we encapsulated Au@Pt core-shell nanoparticles (Au@PtNPs) in the hydrogel to
      generate quantitative readout in a volumetric bar-chart chip (V-Chip). In the V
      Chip, Au@PtNPs catalyzes the oxidation of H2O2 to generate O2, which induces
      movement of an ink bar to a concentration-dependent distance for visual
      quantitative readout. Furthermore, to improve the detection limit in complex real
      samples, we introduced an immunoaffinity column (IAC) of OTA to enrich OTA from
      beer. After the enrichment, as low as 1.27 nM (0.51 ppb) OTA can be detected by
      the V-Chip, which satisfies the test requirement (2.0 ppb) by the European
      Commission. The integration of a target-responsive hydrogel with portable
      enrichment by IAC, as well as signal amplification and quantitative readout by a
      simple microfluidic device, offers a new method for portable detection of food
      safety hazard toxin OTA. 

PMID- 25771716
TI  - The development of a green approach for the biosynthesis of silver and gold
      nanoparticles by using Panax ginseng root extract, and their biological
      applications.
AB  - The biosynthesis of nanoparticles has received attention because of the
      development of economic and environmentally friendly technology for the synthesis
      of nanoparticles. The study develops a convenient method for the green synthesis
      of silver and gold nanoparticles by utilizing fresh root extract of the four-year
      old Panax ginseng plant, and evaluated the antimicrobial applications of silver
      nanoparticles against pathogenic microorganisms. P. ginseng is a well-known
      herbal medicinal plant, and its active ingredients are mainly ginsenosides. The
      fresh root of the 4 year old P. ginseng plant has been explored for the synthesis
      of silver and gold nanoparticles without the use of any additional reducing and
      capping agents. The reduction of silver nitrate led to the formation of silver
      nanoparticles within 2 h of reaction at 80 degrees C. The gold nanoparticles were
      also successfully synthesized by the reduction of auric acid at 80 degrees C,
      within 5 min of reaction. The biosynthesized gold and silver nanoparticles were
      characterized by techniques using various instruments, viz. ultraviolet-visible
      spectroscopy (UV-Vis spectroscopy), field emission transmission electron
      microscopy (FE-TEM), energy dispersive X-ray analysis (EDX), elemental mapping,
      and X-ray diffraction (XRD). In addition, the silver nanoparticles have shown
      antimicrobial potential against Bacillus anthracis, Vibrio parahaemolyticus,
      Staphylococcus aureus, Escherichia coli, and Bacillus cereus. 

PMID- 25771717
TI  - Corrigendum. Measurement precision of body composition variables in elite
      wheelchair athletes, using dual-energy X-ray absorptiometry.

PMID- 25771718
TI  - Influence of whitening and regular dentifrices on orthodontic clear ligature
      color stability.
AB  - OBJECTIVES: This study evaluated the effect of brushing orthodontic clear
      ligatures with a whitening dentifrice containing a blue pigment (Close Up White
      Now, Unilever, London, UK) on their color stability, when exposed to a staining
      agent. MATERIALS AND METHODS: Ligatures from 3M Unitek (Monrovia, CA, USA) and
      Morelli (Sorocaba, SP, Brazil) were tested. Baseline color measurements were
      performed and nonstained groups (control) were stored in distilled water whereas
      test groups were exposed for 1 hour daily to red wine. Specimens were brushed
      daily using regular or whitening dentifrice. Color measurements were repeated
      after 7, 14, 21, and 28 days using a spectrophotometer based on the CIE L*a*b*
      system. RESULTS: Decreased luminosity (CIE L*), increased red discoloration (CIE
      a* axis), and increased yellow discoloration (CIE b* axis) were generally
      observed for ligatures exposed to the staining agent. Color variation was
      generally lower in specimens brushed with regular dentifrice, but ligatures
      brushed with whitening dentifrice were generally less red and less yellow than
      regular dentifrice. The whitening dentifrice led to blue discoloration trend,
      with visually detectable differences particularly apparent according to storage
      condition and ligature brand. CONCLUSIONS: The whitening dentifrice containing
      blue pigment did not improve the ligature color stability, but it decreased
      yellow discoloration and increased a blue coloration. CLINICAL SIGNIFICANCE: The
      use of a whitening dentifrice containing blue pigment during orthodontic
      treatment might decrease the yellow discoloration of elastic ligatures.

PMID- 25771719
TI  - Provider attitudes about childbearing and knowledge of safer conception at two
      HIV clinics in Malawi.
AB  - BACKGROUND: There is limited understanding of health care providers' attitudes
      towards HIV-infected individuals' reproductive choices, as well as knowledge
      about safer conception. Our study objective was to explore provider-level factors
      that serve as barriers and/or facilitators to the provision of reproductive and
      safer conception services for men and women living with HIV. METHODS: Twenty-five
      providers were interviewed in four focus group discussions about their attitudes
      regarding childbearing by HIV-infected clients, reproductive health and HIV
      knowledge, and views and knowledge of safer conception. RESULTS: Providers
      reported ambivalence about supporting childbearing among their clients with HIV.
      They raised concerns about HIV-infected individuals having children, and in
      certain cases expressed judgment that people with HIV should not have children
      because of these concerns. Providers lack specific knowledge about safer
      conception strategies and have low level of knowledge of reproductive health, the
      efficacy of PMTCT, and the risks of pregnancy for HIV-infected women.
      CONCLUSIONS: Providers in our setting have complex attitudes about HIV-infected
      clients having children and lack knowledge to appropriately counsel clients about
      reproductive health and safer conception. Our findings highlight need for further
      research in this area as well as the need for provider training in reproductive
      health and safer conception.

PMID- 25771720
TI  - Suppression of DNA-dependent protein kinase sensitize cells to radiation without
      affecting DSB repair.
AB  - Efficient and correct repair of DNA double-strand break (DSB) is critical for
      cell survival. Defects in the DNA repair may lead to cell death, genomic
      instability and development of cancer. The catalytic subunit of DNA-dependent
      protein kinase (DNA-PKcs) is an essential component of the non-homologous end
      joining (NHEJ) which is the major DSB repair pathway in mammalian cells. In the
      present study, by using siRNA against DNA-PKcs in four human cell lines, we
      examined how low levels of DNA-PKcs affected cellular response to ionizing
      radiation. Decrease of DNA-PKcs levels by 80-95%, induced by siRNA treatment,
      lead to extreme radiosensitivity, similar to that seen in cells completely
      lacking DNA-PKcs and low levels of DNA-PKcs promoted cell accumulation in G2/M
      phase after irradiation and blocked progression of mitosis. Surprisingly, low
      levels of DNA-PKcs did not affect the repair capacity and the removal of 53BP1 or
      gamma-H2AX foci and rejoining of DSB appeared normal. This was in strong contrast
      to cells completely lacking DNA-PKcs and cells treated with the DNA-PKcs
      inhibitor NU7441, in which DSB repair were severely compromised. This suggests
      that there are different mechanisms by which loss of DNA-PKcs functions can
      sensitize cells to ionizing radiation. Further, foci of phosphorylated DNA-PKcs
      (T2609 and S2056) co-localized with DSB and this was independent of the amount of
      DNA-PKcs but foci of DNA-PKcs was only seen in siRNA-treated cells. Our study
      emphasizes on the critical role of DNA-PKcs for maintaining survival after
      radiation exposure which is uncoupled from its essential function in DSB repair.
      This could have implications for the development of therapeutic strategies aiming
      to radiosensitize tumors by affecting the DNA-PKcs function. 

PMID- 25771721
TI  - Deficiency of the DNA repair protein nibrin increases the basal but not the
      radiation induced mutation frequency in vivo.
AB  - Nibrin (NBN) is a member of a DNA repair complex together with MRE11 and RAD50.
      The complex is associated particularly with the repair of DNA double strand
      breaks and with the regulation of cell cycle check points. Hypomorphic mutation
      of components of the complex leads to human disorders characterised by
      radiosensitivity and increased tumour occurrence, particularly of the lymphatic
      system. We have examined here the relationship between DNA damage, mutation
      frequency and mutation spectrum in vitro and in vivo in mouse models carrying NBN
      mutations and a lacZ reporter plasmid. We find that NBN mutation leads to
      increased spontaneous DNA damage in fibroblasts in vitro and high basal mutation
      rates in lymphatic tissue of mice in vivo. The characteristic mutation spectrum
      is dominated by single base transitions rather than the deletions and complex
      rearrangements expected after abortive repair of DNA double strand breaks. We
      conclude that in the absence of wild type nibrin, the repair of spontaneous
      errors, presumably arising during DNA replication, makes a major contribution to
      the basal mutation rate. This applies also to cells heterozygous for an NBN null
      mutation. Mutation frequencies after irradiation in vivo were not increased in
      mice with nibrin mutations as might have been expected considering the
      radiosensitivity of NBS patient cells in vitro. Evidently apoptosis is efficient,
      even in the absence of wild type nibrin. 

PMID- 25771722
TI  - BsmI polymorphism of vitamin D receptor gene and cancer risk: a comprehensive
      meta-analysis.
AB  - The VDR gene is an important regulator of the vitamin D pathway, and the role of
      some of its polymorphisms on cancer risk was previously investigated. A trend of
      cancer risk reduction with the VDR BsmI B allele was observed for many cancer
      sites. We performed a comprehensive meta-analysis to investigate the role of VDR
      BsmI polymorphism on cancer risk, even according to different ethnicities.
      Summary odds ratios (SORs) were calculated with random-effects models and maximum
      likelihood estimation. We categorized studies into three groups ("moderate",
      "high" and "very high confidence") according to departure from Hardy-Weinberg
      equilibrium in controls, reported minor allele frequency and genotyping quality
      controls. The meta-analysis included 73 studies with 45,218 cases and 52,057
      controls. We found a significant 6-7% reduction of cancer risk at any site
      respectively for carriers of Bb genotype (SOR; 95%CI: 0.94; 0.90-0.99) and for
      carriers of BsmI BB genotype (SOR; 95%CI: 0.93; 0.89-0.98) compared to bb
      carriers, and they remain statistically significant when we restricted the
      analysis to at least "high confidence" studies. For skin cancer, a significant
      risk reduction was observed for Bb carriers (SOR; 95%CI: 0.86; 0.76-0.98). We
      also found a significant reduction of colorectal cancer risk for BB and Bb+BB
      genotypes carriers, but these SORs were no more significant when we restricted
      the analysis to studies with "high confidence". When the analysis was stratified
      by ethnicity, we still observed a significant decreased risk for both Bb and BB
      compared to bb genotype among Caucasians: SORs (95%CI) for any cancer site were
      0.97 (0.93-1.00) and 0.95 (0.91-0.99), respectively. Among other ethnic groups
      the inverse association was still present, but did not reach statistical
      significance. In conclusion, we suggest a weak effect of BsmI B allele in
      reducing cancer risk at any site, especially of the skin. 

PMID- 25771723
TI  - A common genetic variation in the promoter of miR-107 is associated with gastric
      adenocarcinoma susceptibility and survival.
AB  - BACKGROUND: Global miRNA expression profile has been widely used to characterize
      human cancers. It is well established that genetic variants in miRNAs can
      modulate miRNA biogenesis and disease risk. METHODS: Genome-wide miRNA microarray
      was employed for assessment of miRNA expression profile of gastric adenocarcinoma
      (GAC). The variants of significantly dysregulated miRNA were genotyped in test
      (715 cases and 804 controls) and validation (940 cases and 1050 controls) subject
      sets. RESULTS: MiRNA microarray revealed that 12 miRNAs including miR-107
      significantly dysregulated in GAC tissues. The sequencing of the promoter of miR
      107 identified 3 SNPs (rs11185777, rs78591545, and rs2296616) with minor allele
      frequency (MAF)>5%. Analyzing their association with GAC risk and prognosis
      revealed that the C allele of rs2296616 (T>C) was significantly associated with
      the decreased risk of GAC among the test, validation and combined sets (TC/CC vs.
      TT, adjusted OR=0.39, 95% CI=0.31-0.49 for the combined set). However, the C
      allele was related to an unfavorable prognosis of Cardia GAC (CGAC) (adjusted
      HR=1.49, 95% CI=1.01-2.20). In vivo evidence showed that the individuals with the
      rs2296616C allele had lower miR-107 expression compared with the homozygous T
      allele carriers. CONCLUSION: miR-107 is dysregulated in GAC pathogenesis and the
      SNP rs2296616 may play a role in the process.

PMID- 25771724
TI  - Induction and repair of DNA damage measured by the comet assay in human T
      lymphocytes separated by immunomagnetic cell sorting.
AB  - The comet assay is widely used in human biomonitoring to measure DNA damage in
      whole blood or isolated peripheral blood mononuclear cells (PBMC) as a marker of
      exposure to genotoxic agents. Cytogenetic assays with phytohemagglutinin (PHA)
      stimulated cultured T lymphocytes are also frequently performed in human
      biomonitoring. Cytogenetic effects (micronuclei, chromosome aberrations, sister
      chromatid exchanges) may be induced in vivo but also occur ex vivo during the
      cultivation of lymphocytes as a consequence of DNA damage present in lymphocytes
      at the time of sampling. To better understand whether DNA damage measured by the
      comet assay in PBMC is representative for DNA damage in T cells, we comparatively
      investigated DNA damage and its repair in PBMC and T cells obtained by
      immunomagnetic cell sorting. PBMC cultures and T cell cultures were exposed to
      mutagens with different modes of genotoxic action and DNA damage was measured by
      the comet assay after the end of a 2h exposure and after 18h post-incubation. The
      mutagens tested were methyl methanesulfonate (MMS), (+/-)-anti-B[a]P-7,8
      dihydrodiol-9,10-epoxide (BPDE), 4-nitroquinoline-1-oxide (4NQO), styrene oxide
      and potassium bromate. MMS and potassium bromate were also tested by the modified
      comet assay with formamido pyrimidine glycosylase (FPG) protein. The results
      indicate that the mutagens tested induce DNA damage in PBMC and T cells in the
      same range of concentrations and removal of induced DNA lesions occurs to a
      comparable extent. Based on these results, we conclude that the comet assay with
      PBMC is suited to predict DNA damage and its removal in T cells. 

PMID- 25771725
TI  - Benzo[a]pyrene-induced cell cycle arrest in HepG2 cells is associated with
      delayed induction of mitotic instability.
AB  - The environmental carcinogen benzo[a]pyrene (B[a]P) after being metabolised by
      cytochrome P450 enzymes forms DNA adducts. This abnormal situation induces
      changes in the cell cycle, DNA damage, chromosomal and mitotic aberrations, all
      of which may be related to carcinogenesis. In order to further investigate the
      mechanistic basis of these effects, HepG2 cells were treated with 3MUM B[a]P for
      various time periods, followed by further incubation in the absence of B[a]P for
      up to 192h. B[a]P treatment led initially to S-phase arrest followed by recovery
      and subsequent induction of G2/M arrest, indicating activation of the
      corresponding DNA damage checkpoints. Immunofluorescence-based studies revealed
      accumulation of B[a]P-induced DNA adducts and chromosomal damage which persisted
      beyond mitosis and entry into a new cycle, thus giving rise to a new round of
      activation of the S-phase checkpoint. Prolonged further cultivation of the cells
      in the absence of B[a]P resulted in high frequencies of various abnormal mitotic
      events. Abrogation of the B[a]P-induced S-phase arrest by the Chk1 inhibitor UCN
      01 triggered a strong apoptotic response but also dramatically decreased the
      frequency of mitotic abnormalities in the surviving cells, suggesting that events
      occurring during S-phase arrest contribute to the formation of delayed mitotic
      damage. Overall, our data demonstrate that, although S-phase arrest serves as a
      mechanism by which the cells reduce their load of genetic damage, its prolonged
      activation may also have a negative impact on the balance between cell death and
      heritable genetic damage. 

PMID- 25771726
TI  - Conserved motifs of MutL proteins.
AB  - The MutL protein is best known for its function in DNA mismatch repair (MMR).
      However, there is evidence to suggest that MutL is not only the linker connecting
      the functions of MutS and MutH in MMR, but that it also participates in other
      repair systems, such as Very Short Patch (VSP), Base Excision (BER) and
      Nucleotide Excision Repair (NER). This study set out to identify the most highly
      conserved amino acid sequence motifs in MutL proteins. We analyzed 208 MutL amino
      acid sequences of 199 representative prokaryotic species belonging to 28 classes
      of bacteria and archaea. The analysis revealed 16 conserved motifs situated in
      the ATPase and endonuclease domains, as well as within the disordered loop, and
      in the MutL regions interacting with the beta clamp of DNA polymerase III. The
      conserved sequence motifs thus determined constitute a structural definition of
      MutL and they may be used in site-directed mutagenesis studies. We found
      conserved residues within the potential regions where binding with MutS occurs.
      However, the existing data does not provide clues as to the possible sites of
      MutL interactions with the proteins involved in other DNA repair systems such as
      NER, BER and VSP. We determined the 57 most highly conserved amino acid residues,
      including 43 which were identical in all the sequences analyzed. The greater part
      of the most predominantly conserved amino acid residues identified in MutL are
      identical to the corresponding residues reported as mutational hot-spots in one
      of its human homologues, MLH1, but not in the other, PMS2. This is the first
      study to present the conserved sequence motifs of MutL widespread in bacteria and
      archaea and the classification of MutLs into five groups distinguished on the
      basis of differences in the C-terminal region. Our analysis is of use in better
      understanding MutL functions. 

PMID- 25771727
TI  - The analysis of S. cerevisiae cells deleted for mitotic cyclin Clb2 reveals a
      novel requirement of Sgs1 DNA helicase and Exonuclease 1 when replication forks
      break in the presence of alkylation damage.
AB  - In this study, we report the effects of deleting the principal mitotic cyclin,
      Clb2, in different repair deficient contexts on sensitivity to the alkylating DNA
      damaging agent, methyl methanesulphonate (MMS). A yeast clb2 mutant is sensitive
      to MMS and displays synergistic effect when combined with inactivation of
      numerous genes involved in DNA recombination and replication. In contrast, clb2
      has basically no additional effect with deletion of the RecQ helicase SGS1, the
      exonuclease EXO1 and the protein kinase RAD53 suggesting that Clb2 functions in
      these pathways. In addition, clb2 increases the viability of the mec1 kinase
      deficient mutant, suggesting Mec1 inhibits a deleterious Clb2 activity.
      Interestingly, we found that the rescue by EXO1 deletion of rad53K227 mutant,
      deficient in checkpoint activation, requires Sgs1, suggesting a role for Rad53,
      independent of its checkpoint function, in regulating an ordered recruitment of
      Sgs1 and Exo1 to fork structure. Overall, our data suggest that Clb2 affects
      recombinant structure of replication fork blocked by alkylating DNA damage at
      numerous steps and could regulate Sgs1 and Exo1 activity. In addition, we found
      novel requirement of Sgs1 DNA helicase and Exonuclease 1 when replication forks
      breaks in the presence of alkylation damage. Models for the functional
      interactions of mitotic cyclin Clb2, Sgs1 and Exo1 with replication fork
      stabilization are proposed. 

PMID- 25771728
TI  - Enhanced DNA repair of bleomycin-induced 3'-phosphoglycolate termini at the
      transcription start sites of actively transcribed genes in human cells.
AB  - The anti-tumour agent, bleomycin, cleaves DNA to give 3'-phosphoglycolate and 5'
      phosphate termini. The removal of 3'-phosphoglycolate to give 3'-OH ends is a
      very important step in the DNA repair of these lesions. In this study, next
      generation DNA sequencing was utilised to investigate the repair of these 3'
      phosphoglycolate termini at the transcription start sites (TSSs) of genes in HeLa
      cells. The 143,600 identified human TSSs in HeLa cells comprised 82,596 non
      transcribed genes and 61,004 transcribed genes; and the transcribed genes were
      divided into quintiles of 12,201 genes comprising the top 20%, 20-40%, 40-60%, 60
      80%, 80-100% of expressed genes. Repair of bleomycin-induced 3'-phosphoglycolate
      termini was enhanced at actively transcribed genes. The top 20% and 20-40%
      quintiles had a very similar level of enhanced repair, the 40-60% quintile was
      intermediate, while the 60-80% and 80-100% quintiles were close to the low level
      of enhancement found in non-transcribed genes. There were also interesting
      differences regarding bleomycin repair on the sense and antisense strands of DNA
      at TSSs. The sense strand had highly enhanced repair between 0 and 250bp relative
      to the TSS, while for the antisense strand highly enhanced repair was between 150
      and 450bp. Repair of DNA damage is a major mechanism of resistance to anti-tumour
      drugs and this study provides an insight into this process in human tumour cells.

PMID- 25771729
TI  - Occurrence of low frequency PIK3CA and AKT2 mutations in gastric cancer.
AB  - The PI3K/AKT signal transduction pathway has distinct functional roles in tumor
      progression. PIK3CA was reported to harbor the hot-spot in many types of tumor.
      Akt, the downstream of PI3K, its family members especially AKT2 activation in
      human cancer has been extensively studied, but its activation by mutation was
      less reported. The occurrence of PIK3CA and AKT2 mutations in a variety of
      cancers indicates their important involvement in carcinogenesis. Therefore, we
      investigated their mutation frequencies in gastric cancer (GC) in China. In our
      study, we selected hot-spot related exons 9, 18 and 20 of PIK3CA and kinase
      domain exons 6-14 of AKT2 genes were screened in 10 GC cell lines, 100 advanced
      primary GC and matched normal tissues. Denaturing high performance liquid
      chromatography (DHPLC) and DNA sequencing were used to analyze the mutations in
      the two genes. Two point mutations in the PIK3CA gene were identified in 4 of 10
      GC cell lines and in 4 of 100 GC primary tumors. Two polymorphisms in AKT2 were
      detected in 19 of 100 GC primary tumors. One point mutation in AKT2 was detected
      in 1 of 10 GC cell lines and 3 of 100 GC primary tumors but no hot spot variation
      was detected. Our results indicate that PIK3CA and AKT2 mutations occurred at low
      frequency in GC, and suggest that the PIK3CA/AKT2 pathway might engage other
      events during gastric carcinogenesis. 

PMID- 25771730
TI  - In vitro cytotoxicity of silver nanoparticles and zinc oxide nanoparticles to
      human epithelial colorectal adenocarcinoma (Caco-2) cells.
AB  - With the increasing applications of silver nanoparticles (Ag NPs) and zinc oxide
      nanoparticles (ZnO NPs) in foods and cosmetics, the concerns about the potential
      toxicities to human have been raised. The aims of this study are to observe the
      cytotoxicity of Ag NPs and ZnO NPs to human epithelial colorectal adenocarcinoma
      (Caco-2) cells in vitro, and to discover the toxicity mechanism of nanoparticles
      on Caco-2 cells. Caco-2 cells were exposed to 10, 25, 50, 100, 200MUg/mL of Ag
      NPs and ZnO NPs (90nm). AO/EB double staining was used to characterize the
      morphology of the treated cells. The cell counting kit-8 (CCK-8) assay was used
      to detect the proliferation of the cells. Reactive oxygen species (ROS),
      superoxide dismutase (SOD) and glutathione (GSH) assay were used to explore the
      oxidative damage of Caco-2 cells. The results showed that Ag NPs and ZnO NPs (0
      200MUg/mL) had highly significant effect on the Caco-2 cells activity. ZnO NPs
      exerted higher cytotoxicity than Ag NPs in the same concentration range. ZnO NPs
      have dose-depended toxicity. The LD50 of ZnO NPs in Caco-2 cells is 0.431mg/L.
      Significant depletion of SOD level, variation in GSH level and release of ROS in
      cells treated by ZnO NPs were observed, which suggests that cytotoxicity of ZnO
      NPs in intestine cells might be mediated through cellular oxidative stress. While
      Caco-2 cells treated with Ag NPs at all experimental concentrations showed no
      cellular oxidative damage. Moreover, the cells' antioxidant capacity increased,
      and reached the highest level when the concentration of Ag NPs was 50MUg/mL.
      Therefore, it can be concluded that Ag NPs are safer antibacterial material in
      food packaging materials than ZnO NPs. 

PMID- 25771731
TI  - MutY-glycosylase: an overview on mutagenesis and activities beyond the GO system.
AB  - MutY is a glycosylase known for its role in DNA base excision repair (BER). It is
      critically important in the prevention of DNA mutations derived from 7,8-dihydro
      8-oxoguanine (8-oxoG), which are the major lesions resulting from guanine
      oxidation. MutY has been described as a DNA repair enzyme in the GO system
      responsible for removing adenine residues misincorporated in 8-oxoG:A mispairs,
      avoiding G:C to T:A mutations. Further studies have shown that this enzyme binds
      to other mispairs, interacts with several enzymes, avoids different
      transversions/transitions in DNA, and is involved in different repair pathways.
      Additional activities have been reported for MutY, such as the repair of
      replication errors in newly synthesized DNA strands through its glycosylase
      activity. Moreover, MutY is a highly conserved enzyme present in several
      prokaryotic and eukaryotic organisms. MutY defects are associated with a
      hereditary colorectal cancer syndrome termed MUTYH-associated polyposis (MAP).
      Here, we have reviewed the roles of MutY in the repair of mispaired bases in DNA
      as well as its activities beyond the GO system. 

PMID- 25771732
TI  - PCSK9 inhibition in patients with hypercholesterolemia.
AB  - Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a serine protease that
      plays an important role in modulating low-density lipoprotein cholesterol (LDL-C)
      levels by targeting LDL-C receptors for lysosomal degradation. Genetic
      association studies have demonstrated that loss-of-function mutations in PCSK9
      are associated with low plasma LDL-C levels and a reduction in the incidence of
      adverse cardiovascular events. Monoclonal antibodies directed against PCSK9 have
      been developed and have been shown in phase 1, 2, and 3 trials to dramatically
      reduce LDL-C regardless of background lipid-lowering therapy, including in
      clinically challenging populations such as patients intolerant to statin therapy
      and those with familial hypercholesterolemia. To date, the clinical trials have
      not raised any significant safety concerns, with no appreciable excess of
      myalgias, elevation in aminotransferases, or other adverse events. Large,
      cardiovascular outcomes trials are underway to assess definitively the efficacy
      and safety of 3 monoclonal antibodies (evolocumab, alirocumab, and bococizumab),
      while additional non-monoclonal antibody approaches to inhibit PCSK9 continue in
      the early-phase development. 

PMID- 25771733
TI  - Melioidosis in children: a retrospective study.
AB  - BACKGROUND: Melioidosis, caused by Burkholderia pseudomallei, is endemic in
      Singapore and can present as localized or disseminated disease. METHODS:
      Demographic data, clinical features, investigation results, treatments, and
      outcomes in patients aged <16 years diagnosed with melioidosis at KK Women's and
      Children's Hospital between January 2002 and January 2014 were retrospectively
      reviewed. Data for patients with primary skin disease and those with other organ
      involvement were compared. RESULTS: Seventeen children were diagnosed with
      melioidosis. Their median age was 12.5 years (range: 2-15 years). Nine (53%)
      patients presented with localized cutaneous melioidosis and five (29%) with
      localized lymphadenitis, pneumonia, or septic arthritis. The remaining three
      (18%) patients had melioidosis sepsis; two of these patients died from septic
      shock. Treatment included an initial 1-2 weeks of IV antibiotics followed by 3-6
      months of oral combination antibiotics. All cases of localized cutaneous disease
      resolved completely with no recurrences. Three (60%) of the five patients with
      localized involvement of other organ systems achieved complete resolution of
      disease, and the remaining two were lost from follow-up. CONCLUSIONS: Although
      uncommon, melioidosis can occur in children living in endemic regions. Patients
      with localized skin disease have good outcomes with no recurrences. Systemic
      disease can be fatal, especially in the presence of underlying immunodeficiency.
      Diagnosis requires a high index of suspicion, and treatment requires prolonged
      combination antibiotic therapy.

PMID- 25771734
TI  - Chronic recurrent multifocal osteomyelitis with an atypical presentation in an
      adult man.
AB  - We present the case of a 33-year-old man with no significant medical history who
      developed right scapular pain, left-sided sacroiliac joint pain, and lower back
      pain, and was eventually diagnosed with chronic recurrent multifocal
      osteomyelitis (CRMO). Imaging demonstrated multiple scattered T2-hyperintense
      lesions on MRI at the spine and the left SI joint, some of which progressed and
      one regressed in size on follow-up. Histopathology demonstrated only non-specific
      chronic inflammation compatible with CRMO. No evidence of infectious organisms or
      neoplastic processes was found. The pain was relapsing and remitting in nature.
      Laboratory investigations were notable for no evidence of hematologic malignancy
      or infection, but only a mild increase in alkaline phosphatase. This case
      highlights that CRMO, despite being thought of as a childhood-onset disease, can
      present in adults as well, and also provides illustrative examples of imaging and
      histological findings. 

PMID- 25771735
TI  - Genipin-Crosslinked Gelatin-Based Emulgels: an Insight into the Thermal,
      Mechanical, and Electrical Studies.
AB  - The present study discusses about the preparation and characterization (thermal,
      mechanical, and electrical) of the genipin-crosslinked gelatin emulgels. Emulgels
      have gained importance in recent years due to their improved stability than
      emulsions and ability to control the drug release. Mustard oil was used as the
      representative oil. A decrease in the enthalpy and entropy of the formulations
      was observed with the increase in the oil fraction. The mechanical studies
      suggested formation of softer emulgels as the oil fraction was increased. As the
      proportion of the oil fraction was increased in the emulgels, there was a
      corresponding increase in the impedance. The drug release properties from the
      emulgels were also studied. Ciprofloxacin was used as the model antimicrobial
      drug. The drug release was higher from the emulgels whose electrical conductivity
      was higher.

PMID- 25771736
TI  - Ampicillin Nanoparticles Production via Supercritical CO2 Gas Antisolvent
      Process.
AB  - The micronization of ampicillin via supercritical gas antisolvent (GAS) process
      was studied. The particle size distribution was significantly controlled with
      effective GAS variables such as initial solute concentration, temperature,
      pressure, and antisolvent addition rate. The effect of each variable in three
      levels was investigated. The precipitated particles were analyzed with scanning
      electron microscopy (SEM) and Zetasizer Nano ZS. The results indicated that
      decreasing the temperature and initial solute concentration while increasing the
      antisolvent rate and pressure led to a decrease in ampicillin particle size. The
      mean particle size of ampicillin was obtained in the range of 220-430 nm by
      varying the GAS effective variables. The purity of GAS-synthesized ampicillin
      nanoparticles was analyzed in contrast to unprocessed ampicillin by FTIR and
      HPLC. The results indicated that the structure of the ampicillin nanoparticles
      remained unchanged during the GAS process.

PMID- 25771737
TI  - Development and Optimization of Gastro-Retentive Controlled-Release Tablet of
      Calcium-Disodium Edentate and its In Vivo Gamma Scintigraphic Evaluation.
AB  - Medical management of heavy metal toxicity, including radioactive ones, is a
      cause for concern because of their increased use in energy production,
      healthcare, and mining. Though chelating agents like EDTA and DTPA in parenteral
      form are available, no suitable oral formulation is there that can trap ingested
      heavy metal toxicants in the stomach itself, preventing their systemic
      absorption. The objective of the present study was to develop and optimize gastro
      retentive controlled-release tablets of calcium-disodium edentate (Ca-Na2EDTA).
      Gastro-retentive tablet of Ca-Na2EDTA was prepared by direct compression method.
      Thirteen tablet formulations were designed using HPMC-K4M, sodium chloride, and
      carbopol-934 along with effervescing agents sodium bicarbonate and citric acid.
      Tablet swelling ability, in vitro buoyancy, and drug dissolution studies were
      conducted in 0.1 N HCl at 37 +/- 0.5 degrees C. Ca-Na2EDTA was radiolabeled with
      technetium-99m for scintigraphy-based in vivo evaluation. Formula F8 (Ca-Na2EDTA
      200 mg, carbopol 100 mg, avicel 55 mg, citric acid 30 mg, NaHCO3 70 mg, NaCl 100
      mg, and HPMC 95 mg) was found to be optimum in terms of excellent floating
      properties and sustained drug release. F8 fitted best for Korsmeyer-Peppas
      equation with an R (2) value of 0.993. Gamma scintigraphy in humans showed mean
      gastric retention period of 6 h. Stability studies carried out in accordance with
      ICH guidelines and analyzed at time intervals of 0, 1, 2, 4, and 6 months have
      indicated insignificant difference in tablet hardness, drug content, total
      floating duration, or matrix integrity of the optimized formulation. Gastro
      retentive, controlled-release tablet of Ca-Na2EDTA was successfully developed
      using effervescent technique as a potential oral antidote for neutralizing
      ingested heavy metal toxicity.

PMID- 25771739
TI  - Drug in Adhesive Patch of Zolmitriptan: Formulation and In vitro /In vivo
      Correlation.
AB  - The objective of the present study was to develop transdermal patch for
      zolmitriptan, determine its in vivo absorption using the rabbit skin. Solvent
      evaporation technique prepared zolmitriptan patch was settled in two-chamber
      diffusion cell combined with excised rabbit abdomen skin for permeation study. A
      sufficient cumulative penetration amount of zolmitriptan (258.5 +/- 26.9
      MUg/cm(2) in 24 h) was achieved by the formulation of 4% zolmitriptan, 10% Azone,
      and adhesive of DURO-TAK(r) 87-4098. Pharmacokinetic parameters were determined
      via i.v. and transdermal administrations using animal model of rabbit. The
      results revealed that the absolute bioavailability was about 63%. Zolmitriptan
      could be detected with drug level of 88 +/- 51 ng/mL after transdermal
      administration of 15 min. The in vivo absorption curve obtained by deconvolution
      approach using WinNonlin(r) program was correlated well with the in vitro
      permeation curve, the correlation coefficient R is 0.84, and the result indicated
      that in vitro skin permeation experiments were useful to predict the in vivo
      performance. In addition, little skin irritation was found in the irritation
      study. As a conclusion, the optimized zolmitriptan transdermal patches could
      effectively deliver adequate drug into systemic circulation in short time without
      producing any irritation phenomenon and worth to be developed.

PMID- 25771738
TI  - An Investigation on the Effect of Polyethylene Oxide Concentration and Particle
      Size in Modulating Theophylline Release from Tablet Matrices.
AB  - Polyethylene oxide has been researched extensively as an alternative polymer to
      hydroxypropyl methylcellulose (HPMC) in controlled drug delivery due to its
      desirable swelling properties and its availability in a number of different
      viscosity grades. Previous studies on HPMC have pointed out the importance of
      particle size on drug release, but as of yet, no studies have investigated the
      effect of particle size of polyethylene oxide (polyox) on drug release. The
      present study explored the relationship between polymer level and particle size
      to sustain the drug release. Tablets produced contained theophylline as their
      active ingredient and consisted of different polyethylene oxide particle size
      fractions (20-45, 45-90, 90-180 and 180-425 MUm). It was shown that matrices
      containing smaller particle sizes of polyox produced harder tablets than when
      larger polyox particles were used. The release studies showed that matrices
      consisting of large polyox particles showed a faster release rate than matrices
      made from smaller particles. Molecular weight (MW) of the polymer was a key
      determining step in attaining sustained release, with the high MW of polyox
      resulting in a delayed release profile. The results showed that the effect of
      particle size on drug release was more detrimental when a low concentration of
      polyox was used. This indicates that care must be taken when low levels of polyox
      with different particle size fractions are used. More robust formulations could
      be obtained when the concentration of polyox is high. Differential scanning
      calorimetry (DSC) traces showed that particle size had no major effect on the
      thermal behaviour of polyox particles.

PMID- 25771740
TI  - Effect of Cyclodextrins on Morphology and Barrier Characteristics of Isolated
      Rabbit Corneas.
AB  - The objective of the present study is to investigate the confounding effects, if
      any, of beta-cyclodextrins (betaCDs) on corneal permeability coefficients
      obtained from in vitro transmembrane diffusion studies. Transcorneal permeability
      studies were carried out with 2-hydroxypropyl-beta-cyclodextrin (HPbetaCD) and
      randomly methylated-beta-cyclodextrin (RMbetaCD) at 5 and 2.5%w/v in isotonic
      phosphate-buffered solution (IPBS) (pH 7.4). Rabbit corneas received from Pel
      Freez Biologicals(r) were used for these studies. Propranolol hydrochloride
      (PHCl) (1 mg/mL) was used as the paracellular permeability marker. A series of
      permeation studies were carried out with IPBS as the control, with CDs on the
      donor side only, CDs on the receiver side only, and CDs on both the donor and
      receiver sides. At the end of 1 or 3 h, corneas were collected and fixed using a
      solution containing 2%v/v glutaraldehyde + 2%w/v paraformaldehyde + IPBS and
      histological examinations were performed (Excalibur Pathology, Inc). The order of
      transcorneal permeability of PHCl was found to be CDs on the receiver side >
      control (no CDs) ~ CDs on both the receiver and donor sides > CDs on the donor
      side. Histology studies revealed that the corneal epithelial and endothelial
      layers remained intact in the control sets. Damage to the cornea was observed in
      the order of CDs on the receiver side > CDs on the donor side > CDs on both sides
      > control. The use of CDs in solutions for in vitro permeation experiments with
      rabbit corneas needs to be carefully considered to avoid confounding effects in
      the data obtained.

PMID- 25771741
TI  - A Reaction of Aspirin with Ferrous Gluconate.
AB  - A color reaction of aspirin with ferrous gluconate was studied by UV-Vis
      spectrophotometry and HPLC-MS. It was found that the UV-Vis spectra of the two
      drugs were different before and after they were mixed in water at about 0.3 M
      (diluted by >20 times for analysis), indicating that a complexation reaction took
      place. The drug-iron complex dissociated when the reacting solution was diluted
      by 400 times. The by-products of the reaction identified by HPLC-MS were
      salicylic acid, acetylated gluconic acid, salicylate-gluconic acid conjugate, and
      an oxidized product of salicylic acid that was complexed with iron with a
      molecular weight of 212. This reaction may be used as an important consideration
      to optimize the dosing regime of the two drugs and to help explain some
      pharmacological reactions between aspirin and biomolecules.

PMID- 25771742
TI  - Instilling new habits: addressing implicit bias in healthcare professionals.
AB  - There appears to be a fundamental inconsistency between research which shows that
      some minority groups consistently receive lower quality healthcare and the
      literature indicating that healthcare workers appear to hold equality as a core
      personal value. Recent evidence using Implicit Association Tests suggests that
      these disparities in outcome may in part be due to social biases that are
      primarily unconscious. In some individuals the activation of these biases may be
      also facilitated by the high levels of cognitive load associated with clinical
      practice. However, a range of measures, such as counter-stereotypical stimuli and
      targeted experience with minority groups, have been identified as possible
      solutions in other fields and may be adapted for use within healthcare settings.
      We suggest that social bias should not be seen exclusively as a problem of
      conscious attitudes which need to be addressed through increased awareness.
      Instead the delivery of bias free healthcare should become a habit, developed
      through a continuous process of practice, feedback and reflection. 

PMID- 25771743
TI  - Histological observations of pulpal replacement tissue in immature dog teeth
      after revascularization of infected pulps.
AB  - BACKGROUND AND AIM: Many studies have examined the nature of tissue formed in the
      canals of immature necrotic teeth, following revascularization in animals and
      humans. While speculations have been made that regeneration of the pulp tissue
      might take place in the canal, the tissue has been found to be cementum-like,
      bone-like, and periodontal ligament-like. The purpose of this study was to
      histologically examine the tissue in the root canals in immature dog teeth that
      had been artificially infected and then revascularized. METHODS: Two 4- to 5
      month-old mongrel dogs with immature teeth were used in the study. In one dog,
      four maxillary and four mandibular anterior teeth, and in another dog, four
      maxillary and five mandibular anterior teeth were used in the experiment. Pulp
      infection was artificially induced in the immature teeth. Revascularization was
      performed on all teeth by disinfecting the root canals with sodium hypochlorite
      irrigation and triple antibiotic intracanal dressing, completed with induction of
      intracanal bleeding, and sealed with an MTA plug. The access cavity was restored
      with silver amalgam. The animals were sacrificed 3 months after revascularization
      procedures. The revascularized teeth and surrounding periodontal tissues were
      removed and prepared for histological examination. RESULTS: Besides cementum
      like, bone-like, and periodontal ligament-like tissues formed in the canals,
      residual remaining pulp tissue was observed in two revascularized teeth. In four
      teeth, ingrowth of alveolar bone into the canals was seen; presence of bone in
      the root canals has the potential for ankylosis. CONCLUSIONS: Within the
      limitation of this study, it can be concluded that residual pulp tissue can
      remain in the canals after revascularization procedures of immature teeth with
      artificially induced pulp infection. This can lead to the misinterpretation that
      true pulpal regeneration has occurred. Ingrowth of apical bone into the root
      canals undergoing revascularization can interfere with normal tooth eruption if
      ankylosis occurs.

PMID- 25771744
TI  - Surgical treatment of a floating thrombus of the ascending aorta causing repeated
      arterial embolisms.
AB  - Floating thrombus of the ascending aorta is a rare and often ignored cause of
      peripheral embolic events. We report the observation of a patient presenting
      recurrent peripheral embolic demonstrations: acute ischemia of the right lower
      limb complicated of a thigh amputation and transient cerebrovascular accident.
      The assessment by angioscanner highlighted a 40-mm thrombus of the ascending
      aorta. The thrombus was removed surgically. This diagnosis should not be ignored
      in the assessment of an embolic pathology with the risk of severe functional
      after-effects caused by an important diagnostic delay. 

PMID- 25771745
TI  - "Lower limbs revascularization from supraceliac and thoracic aorta".
AB  - Revascularization of femoral arteries from descending thoracic or supraceliac
      aorta is an uncommon procedure, in part because of the popularization of the
      technically easier extra-anatomic bypasses. However, using those aortic levels as
      the source of the bypass inflow is a useful alternative in selected patients with
      aortoiliac disease, with excellent results. We report long-term results in 4
      patients with revascularization from thoracic aorta and another 2 cases from
      aorta at supraceliac level. This technique should be considered as a good
      alternative in patients with adverse abdominal conditions or with a severely
      diseased infrarenal aorta due to heavy calcification. 

PMID- 25771747
TI  - Patient-centered medical homes may reduce emergency department use: what does
      this tell us?

PMID- 25771746
TI  - Long-term effects of castration on the skeleton of male rhesus monkeys (Macaca
      mulatta).
AB  - While osteopenia (OPE) and osteoporosis (OPO) have been studied in various
      species of aging nonhuman primates and extensively in ovariectomized rhesus and
      cynomolgus macaques, there is virtually no information on the effects of
      castration on the skeleton of male nonhuman primates. Most information on
      castrated male primates comes from a few studies on the skeletons of eunuchs.
      This report used a subset of the Caribbean Primate Research Center's (CPRC) Cayo
      Santiago (CS) rhesus macaque skeletal collection to qualitatively and
      quantitatively compare the bone mineral density (BMD) of castrated and age
      matched intact males and, thereby, determine the long-term effects of castration
      (orchidectomy) on bone. Lumbar vertebrae, femora, and crania were evaluated using
      dual-energy X-ray absorptiometry (DEXA or DXA) and digital radiography augmented,
      when fresh tissues were available, with autoradiography and histology. Results
      confirmed physical examinations of long bones that castration causes changes in
      the skeleton of male rhesus macaques similar to those found in eunuchs, including
      OPE and OPO of the vertebrae and femora, thinning of the skull, and vertebral
      fractures and kyphosis of the spine more severe than that caused by normal aging
      alone. Also like eunuchs, some castrated CS male rhesus monkeys had a longer life
      span than intact males or females. Based on these results and the effects of
      castration on other tissues and organs of eunuchs, on behavior, hormone profiles
      and possibly on cognition and visual perception of human and nonhuman primates,
      and other mammals, castrated male rhesus macaques should be used with caution for
      laboratory studies and should be considered a separate category from intact
      males. Despite these caveats, the castrated male rhesus macaque should make an
      excellent animal model in which to test hormone replacement therapies for boys
      and men orchidectomized for testicular and prostate cancer.

PMID- 25771748
TI  - Fabrication of elastomeric scaffolds with curvilinear fibrous structures for
      heart valve leaflet engineering.
AB  - Native semi-lunar heart valves are composed of a dense fibrous network that
      generally follows a curvilinear path along the width of the leaflet. Recent
      models of engineered valve leaflets have predicted that such curvilinear fiber
      orientations would homogenize the strain field and reduce stress concentrations
      at the commissure. In the present work, a method was developed to reproduce this
      curvilinear fiber alignment in electrospun scaffolds by varying the geometry of
      the collecting mandrel. Elastomeric poly(ester urethane)urea was electrospun onto
      rotating conical mandrels of varying angles to produce fibrous scaffolds where
      the angle of fiber alignment varied linearly over scaffold length. By matching
      the radius of the conical mandrel to the radius of curvature for the native
      pulmonary valve, the electrospun constructs exhibited a curvilinear fiber
      structure similar to the native leaflet. Moreover, the constructs had local
      mechanical properties comparable to conventional scaffolds and native heart
      valves. In agreement with prior modeling results, it was found under quasi-static
      loading that curvilinear fiber microstructures reduced strain concentrations
      compared to scaffolds generated on a conventional cylindrical mandrels. Thus,
      this simple technique offers an attractive means for fabricating scaffolds where
      key microstructural features of the native leaflet are imitated for heart valve
      tissue engineering.

PMID- 25771749
TI  - Oxygen uptake and heart rate kinetics during dynamic upper and lower body
      exercise: an investigation by time-series analysis.
AB  - PURPOSE: The study compared the kinetic responses of heart rate (HR), pulmonary
      ([Formula: see text]O2pulm) and muscular oxygen uptake ([Formula: see
      text]O2musc) for upper (UpBody) and lower body (LoBody) exercise. METHODS: Eleven
      healthy men (24 +/- 2 years, 184 +/- 8 cm, 79 +/- 7 kg) performed pseudo-random
      binary sequence (PRBS) work rate (WR) changes on a semi-recumbent cycle ergometer
      (30 and 80 W) and an arm cranking exercise device (20 and 50 W); followed by
      stepwise increases in WR (UpBody: 20 W 5 min(-1); LoBody: 50 W 5 min(-1)).
      [Formula: see text]O2pulm was measured breath-by-breath and HR beat-to-beat.
      [Formula: see text]O2musc was estimated by the approach as reported by Hoffmann
      et al. (Eur J Appl Physiol 113:1745-1754, 2013), accounting for circulatory
      distortions. Time constants (tau) for HR (tauHR), [Formula: see text]O2pulm (tau
      [Formula: see text]O2pulm) and [Formula: see text]O2musc (tau [Formula: see
      text]O2musc) were estimated during the PRBS phases by time-series analysis.
      RESULTS: Peak oxygen uptake differed significantly between UpBody (37.8 +/- 5.0
      ml min(-1) kg(-1)) and LoBody exercises (56.1 +/- 7.4 mL min(-1) kg(-1); p <
      0.001). Significant differences were observed for tau [Formula: see text]O2musc
      (UpBody: 41.1 +/- 11.3 s vs LoBody: 29.5 +/- 5.2 s; p < 0.05), but not for tau
      [Formula: see text]O2pulm (49.1 +/- 17.1 s vs 39.6 +/- 11.2 s; p > 0.05) and
      tauHR (29.1 +/- 15.6 s vs 25.6 +/- 8.0 s; p > 0.05). CONCLUSIONS: Meaningful
      dissociations between [Formula: see text]O2pulm and [Formula: see text]O2musc
      kinetics exist for both UpBody and LoBody exercise during rapid work rate
      changes. Therefore, isolated [Formula: see text]O2pulm kinetic estimations
      without the consideration of the circulatory distortions may not allow a reliable
      assessment of [Formula: see text]O2musc kinetics.

PMID- 25771750
TI  - Frequency and genotype of human parvovirus B19 among Iranian patients infected
      with HIV.
AB  - The human parvovirus B19 (B19) usually causes a subclinical infection in
      immunocompetent individuals. Whereas immunocompromised individuals such as
      patients infected with HIV are at risk of persistent anemia due to B19 infection.
      Only few studies have been carried out on distribution and molecular epidemiology
      of B19 in Iran. We aimed to determine the frequency and genotype of B19 among
      Iranian patients infected with HIV. We conducted a survey on 99 HIV patients and
      64 healthy controls. IgG and IgM antibodies against B19 were detected by ELISA
      and B19 DNA was assessed by nested PCR. PCR products were subjected to direct
      sequencing and classified after phylogenetic analysis. The prevalence of B19
      immunoglobulin was 11.1% for IgG and 1% for IgM. B19 DNA was detected in 13.1% of
      cases. The prevalence of B19 IgG, IgM, and DNA in control group was 25%, 1.6%,
      and 9.4%, respectively. B19 IgG was significantly lower in HIV group than in
      normal controls. There was no significant difference regarding anemia between
      cases and controls. All sequenced B19 isolates belonged to genotype 1A with low
      genetic diversity. Our findings indicated that in the HAART era, the importance
      of B19 infections in HIV patients may be limited whereas persistent B19 viremia
      in the circulation of healthy controls raises a potential concern in blood
      donations.

PMID- 25771751
TI  - Prevalence and comorbidity of eating disorders among a community sample of
      adolescents: 2-year follow-up.
AB  - The previous literature about comorbidity between eating disorders (ED) and other
      DSM-IV psychiatric disorders in adolescence has employed cross-sectional studies
      with clinical samples, where the comorbid disorders were diagnosed
      retrospectively. The present study aims to overcome these limitations by the
      analysis of comorbidity in a community population during 2-year follow-up. A semi
      structured interview was applied to a teenager sample. Firstly, a cross-sectional
      and non-randomized study on psychiatric morbidity was conducted with 993
      teenagers between the ages of 12 and 16 from five schools. Secondly, 326 students
      between 14 and 17 years old of one school were reassessed 2 years later in order
      to detect ED new cases and find associations with previous psychiatric disorders.
      The ED prevalence was 3.6%. Cross-sectional analysis revealed that 62.9% of
      individuals with an ED had comorbid disorders: anxiety disorders (51.4%),
      Attention Deficit Hyperactivity Disorder (31.4%), oppositional defiant disorder
      (11.4%), and obsessive compulsive disorder (8.6%). Prospective longitudinal
      analysis showed an ED incidence rate of 2.76% over the course of 2 years. 22.2%
      of new cases had received previous psychiatric diagnoses, of which all were
      anxiety disorders. Thus, ED exhibited a high comorbidity rate among adolescent
      populations and anxiety disorders were the most common comorbid diagnosis. 

PMID- 25771752
TI  - Cognitive-behavioral therapy for pediatric obsessive-compulsive disorder:
      Empirical review and clinical recommendations.
AB  - The efficacy of cognitive-behavioral therapy (CBT) for pediatric obsessive
      compulsive disorder (OCD) has been the subject of much study over the past
      fifteen years. Building on a foundation of case studies and open clinical trials,
      the literature now contains many methodologically sound studies that have
      compared full CBT protocols to waitlist controls, pill placebo, psychosocial
      comparison conditions, active medication, combined treatments, and brief CBT.
      This review is part of a series commissioned by The Canadian Institute for
      Obsessive Compulsive Disorders (CIOCD) in an effort to publish in one place what
      is known about the efficacy of treatments for OCD. A total of fourteen studies
      were identified; collectively their findings support the efficacy of CBT for
      youth with OCD. CBT protocols that emphasized either strictly behavioral or
      cognitive conceptualizations have each been found efficacious relative to
      waitlist controls. Efforts to enhance CBT's efficacy and reach have been
      undertaken. These trials provide guidance regarding next steps to be taken to
      maximize efficacy and treatment availability. Findings from studies in community
      clinics suggest that significant treatment benefits can be realized and are not
      reported only from within academic contexts. These findings bode well for broader
      dissemination efforts. Recommendations for future research directions are
      provided. 

PMID- 25771753
TI  - Hybrid cross-linking characteristics of hydrogel control stem cell fate.
AB  - Controlling hydrogel structures by combination of physical and chemical cross
      links provides a novel system to regulate (stem) cell fate. In this study, we
      designed a polyethylene glycol (PEG)-based hydrogel where the polymer chains
      contain both physical and chemical cross-linking units in the same chain with
      self-assembling L-tyrosine-based dipeptides and photopolymerizable polyacrylate
      groups, respectively. It is shown that hydrogel architectures derived from this
      polymer are correlated to the cross-linking mechanisms. Combination of these
      cross-links controls three-dimensional gel architecture to regulate stem cell
      behavior in these hydrogels. Particularly, interaction of mesenchymal stem cells
      with the hydrogel enabled cellular aggregation to enhance chondrogenic
      differentiation as observed from the deposition of chondrogenic matrix. Increased
      chondrogenesis was due to enhanced cell-cell adhesion, which was mediated by gel
      morphology. This study shows the interplay of physical and chemical cross-links
      in hydrogels to regulate stem cell function and provides a novel molecular
      engineering tool for controlling hydrogel properties. 

PMID- 25771754
TI  - A rare case of longitudinal Brucella myelitis.

PMID- 25771755
TI  - Biomechanical stability of transverse connectors in the setting of a thoracic
      pedicle subtraction osteotomy.
AB  - BACKGROUND CONTEXT: Transverse connectors (TCs) are often used to improve the
      rigidity of posterior spinal instrumentation as previous investigations have
      suggested that TCs enhance torsional rigidity in long-segment thoracic
      constructs. Posterior osteotomies, such as pedicle subtraction osteotomy (PSO),
      are used in severe thoracic deformities and provide a significant amount of
      correction; as a consequence, however, PSOs also induce three-column spinal
      instability. In theory, augmentation of longitudinal constructs with TC after a
      thoracic PSO may provide additional rigidity, but the concept has not been
      previously evaluated. PURPOSE: To evaluate the biomechanical contribution of TC
      to the rigidity of a long-segment pedicle screw-rod construct after a thoracic
      PSO. STUDY DESIGN: An in vitro fresh-frozen human cadaveric biomechanical
      analysis. METHODS: Seven human cadaveric thoracic spines were prepared and
      instrumented from T4-T10 with bilateral pedicle screws/rods and a PSO was
      performed at T7. Intact range of motion (ROM) testing was performed with
      nondestructive loading and analyzed by loading modality (axial rotation [AR],
      flexion/extension [FE], and lateral bending [LB]). Range of motion analysis was
      performed in the unaugmented construct, the construct augmented with one TC, and
      the construct augmented with two TCs. RESULTS: After PSO and an unaugmented
      longitudinal pedicle screw-rod construct, T4-T10 (overall construct) and T6-T8
      (PSO site) ROMs were significantly reduced in all planes of motion compared with
      intact condition (AR: 11.8 degrees  vs. 31.7 degrees ; FE: 2.4 degrees  vs. 12.3
      degrees ; 3.4 degrees  vs. 17.9 degrees , respectively, p<.05). Augmentation of
      longitudinal construct with either one or two TCs did not significantly increase
      construct rigidity in FE or LB compared with the unaugmented construct (p>.05).
      In contrast, during AR, global ROM was significantly reduced by 43% and 48% at T6
      T8 (1.7 degrees  and 1.2 degrees  vs. 2.38 degrees , respectively) after addition
      of one and two TCs (p<.05), respectively. One TC did not significantly reduce
      torsional ROM from the intact state. CONCLUSIONS: Two TCs significantly improved
      torsional rigidity of the entire construct and at the PSO site, with no
      differences in rigidity for FE and LB or with the addition of only one TC. In the
      setting of a PSO and long-segment pedicle screw-rod construct, augmentation with
      at least two TCs should be considered to improve torsional rigidity.

PMID- 25771756
TI  - Outrigger rod technique for supplemental support of posterior spinal arthrodesis.
AB  - BACKGROUND CONTEXT: Instrumentation failure is a recognized complication after
      complex spinal reconstruction and deformity correction. Rod fracture (RF) is the
      most frequent mode of hardware failure in long-segment spinal fusion surgery.
      This complication can negatively impact the clinical outcome by producing spinal
      pain, functional compromise, instability, and loss of deformity correction.
      PURPOSE: To describe the outrigger rod surgical technique. STUDY DESIGN: Review
      of literature, case review, and surgical technique description. PATIENT SAMPLE:
      Two clinical cases are presented. OUTCOME MEASURES: Rod fracture. METHODS:
      Outrigger rod placement in posterior spinal arthrodesis is performed by
      supplementing primary spinal rods with outrigger rods attached with cranial and
      caudal side-by-side connectors providing a more robust construct. RESULTS: This
      technique may be beneficial for preventing RF in patients undergoing surgery for
      three-column osteotomy for sagittal imbalance; pseudarthrosis surgery with
      previous hardware failure; transforaminal lumbar interbody cage placement at
      multiple levels in realignment procedures, long-segment spinal arthrodesis with
      impaired host fusion potential; long-segment instrumented fusions that span the
      cervicothoracic, thoracolumbar, or lumbosacral junction; and across spinal
      segments at high risk for RF (eg, after extensive resection of vertebral elements
      in the management of metastatic malignancy). CONCLUSIONS: The risk of rod failure
      is substantial in the setting of long-segment spinal arthrodesis and corrective
      osteotomy. Efforts to increase the mechanical strength of posterior constructs
      may reduce the occurrence of this complication. The outrigger rod technique
      increases spinal construct stiffness and may improve the longevity of the
      construct. This technique should reduce the rate of device failure during
      maturation of posterior fusion mass and limit the need for supplemental anterior
      column support.

PMID- 25771758
TI  - Benign fibrous histiocytoma of the thoracic spine as the cause of pyrexia of
      unknown origin identified by positron emission tomography/computed tomography.

PMID- 25771757
TI  - Clinical decision rule for primary care patient with acute low back pain at risk
      of developing chronic pain.
AB  - BACKGROUND CONTEXT: Primary care clinicians need to identify candidates for early
      interventions to prevent patients with acute pain from developing chronic pain.
      PURPOSE: We conducted a 2-year prospective cohort study of risk factors for the
      progression to chronic pain and developed and internally validated a clinical
      decision rule (CDR) that stratifies patients into low-, medium-, and high-risk
      groups for chronic pain. STUDY DESIGN/SETTING: This is a prospective cohort study
      in primary care. PATIENT SAMPLE: Patients with acute low back pain (LBP, <=30
      days duration) were included. OUTCOME MEASURES: Outcome measures were self
      reported perceived nonrecovery and chronic pain. METHODS: Patients were surveyed
      at baseline, 6 months, and 2 years. We conducted bivariate and multivariate
      regression analyses of demographic, clinical, and psychosocial variables for
      chronic pain outcomes, developed a CDR, and assessed its performance by
      calculating the bootstrapped areas under the receiver-operating characteristic
      curve (AUC) and likelihood ratios. RESULTS: Six hundred five patients enrolled:
      13% had chronic pain at 6 months and 19% at 2 years. An eight-item CDR was most
      parsimonious for classifying patients into three risk levels. Bootstrapped AUC
      was 0.76 (0.70-0.82) for the 6-month CDR. Each 10-point score increase (60-point
      range) was associated with an odds ratio of 11.1 (10.8-11.4) for developing
      chronic pain. Using a less than 5% probability of chronic pain as the cutoff for
      low risk and a greater than 40% probability for high risk, likelihood ratios were
      0.26 (0.14-0.48) and 4.4 (3.0-6.3) for these groups, respectively. CONCLUSIONS: A
      CDR was developed that may help primary care clinicians classify patients with
      strictly defined acute LBP into low-, moderate-, and high-risk groups for
      developing chronic pain and performed acceptably in 1,000 bootstrapped
      replications. Validation in a separate sample is needed.

PMID- 25771759
TI  - Potential advantages of an additional forearm rubber tourniquet in intravenous
      regional anesthesia: a randomized clinical trial.
AB  - OBJECTIVE: Although the usefulness of an additional forearm tourniquet to
      conventional intravenous regional anesthesia (IVRA) has been reported, the
      forearm cuff may disturb the surgical field to some degree, especially in wrist
      surgery. In the present study, we assessed the clinical efficacy of a temporary
      additional forearm rubber tourniquet to the conventional upper arm tourniquet on
      the quality of IVRA. METHODS: The study included 32 ASA physical status I and II
      adult patients undergoing elective hand surgery who were randomly allocated to
      either an additional forearm tourniquet group (Group F) or to a conventional
      upper arm tourniquet group (Group C). Upper arm tourniquet IVRA was established
      using 40 mL of 0.5 % lidocaine in Group C. Hypothetically enhanced forearm
      tourniquet IVRA was established using 10 mL of 0.5 % lidocaine with an additional
      forearm rubber tourniquet and then administering 30 mL of 0.25 % lidocaine after
      removing the forearm tourniquet in Group F. The sensory and motor block onset and
      recovery times, onset time of tourniquet pain, intraoperative fentanyl
      consumption, and incidence of local anesthetic toxicity were recorded. The
      numerical rating score (NRS) of perioperative and postoperative pain and quality
      of anesthesia were also assessed. RESULTS: Although the total dose of lidocaine
      in Group F was less and the sensory and motor block onset times were
      significantly shorter in Group F than those in Group C (P < 0.05), there was no
      difference regarding sensory and motor block recovery times, onset time of
      tourniquet pain, intraoperative fentanyl consumption, NRS of perioperative and
      postoperative pain, and the quality of anesthesia in the two groups (P > 0.05).
      Compared with Group C, the incidence of local anesthetic toxicity (i.e.,
      dizziness, 43.8 vs 6.2 %, P = 0.02) was significantly decreased in Group F.
      CONCLUSIONS: The combination of the additional forearm and upper arm tourniquets
      with a smaller amount of local anesthetic achieved more rapid onset of sensory
      and motor block, a similar quality of anesthesia and a lower incidence of local
      anesthetic toxicity compared with the conventional technique.

PMID- 25771760
TI  - Effect of a new heated and humidified breathing circuit with a fluid-warming
      device on intraoperative core temperature: a prospective randomized study.
AB  - BACKGROUND: The effect of the Mega Acer kit(@), a new heated and humidified
      breathing circuit (HHBC) containing a fluid-warming device, was investigated on
      intraoperative core temperature (T c). METHODS: A total of 102 patients
      undergoing elective craniotomies were randomly divided into three groups based on
      the breathing circuit used: a conventional breathing circuit (group C, n = 34), a
      Fisher & Paykel HHBC (group F, n = 34), and the Mega (group M, n = 34). From
      baseline to the end of the surgery, T c and infusion fluid temperature (T f) were
      recorded at 15-min intervals. If T c became lower than 35.5  degrees C, a forced
      air warmer was used. RESULTS: Baseline temperatures were 36.7 +/- 0.3, 36.6 +/-
      0.2, and 36.6 +/- 0.2  degrees C in groups C, M, and F, respectively. T c at the
      end of surgery dropped from baseline values by 1.0 +/- 0.4, 0.5 +/- 0.5, and 0.8
      +/- 0.5  degrees C in groups C, M, and F, respectively. From 60 min of post
      induction to the end of surgery, T c was higher in group M than group C (p <
      0.05). From 105 min of post-induction to the end of surgery, T c was higher in
      group M than group F (p < 0.05). The number of patients receiving forced-air
      warmer and total forced-air warmer using time were significantly lower in group M
      than groups C and F (p < 0.05). T f was higher in group M than groups C and F
      throughout the study period (31.0 +/- 1.0 vs. 23.5 +/- 0.5 and 24.0 +/- 0.4 
      degrees C; p < 0.01). CONCLUSIONS: The Mega significantly reduced the drop in
      intraoperative T c by delivering warm fluids, compared with the other breathing
      circuits tested. TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT01831843.

PMID- 25771761
TI  - The impact of inspiratory pressure on stroke volume variation and the evaluation
      of indexing stroke volume variation to inspiratory pressure under various preload
      conditions in experimental animals.
AB  - PURPOSE: Stroke volume variation (SVV) measures fluid responsiveness, enabling
      optimal fluid management under positive pressure ventilation. We aimed to
      investigate the effect of peak inspiratory pressure (PIP) on SVV under various
      preload conditions in experimental animals and to ascertain whether SVV indexed
      to PIP decreases the effect. METHODS: Mild and moderate hemorrhage models were
      created in nine anesthetized, mechanically ventilated beagle dogs by sequentially
      removing 10 and then an additional 10 ml/kg of blood, respectively. In all the
      animals, PIP was incrementally increased by 4 cmH2O, from 5 to 21 cmH2O. SVV was
      measured by arterial pulse contour analysis. Stroke volume was derived using a
      thermodilution method, and central venous pressure and mean arterial pressure
      were also measured. RESULTS: SVV increased according to PIP with significant
      correlation at baseline, with mild hemorrhage and moderate hemorrhage. PIP
      regression coefficients at baseline and in the mild and moderate hemorrhage
      models were 0.59, 0.86, and 1.4, respectively. Two-way repeated-measures analysis
      of variance showed that PIP and the degree of hemorrhage had a significant
      interaction effect on SVV (p = 0.0016). SVV indexed to PIP reflected the
      hemorrhage status regardless of PIP changes >=9 cmH2O. CONCLUSIONS: PIP is
      significantly correlated with SVV, even under hypovolemia, and the effect is
      enhanced with decreasing preload volumes. Compared with SVV, the indexed SVV was
      less susceptible to higher inspiratory pressures.

PMID- 25771762
TI  - Destined for indecision? A critical analysis of waste management practices in
      England from 1996 to 2013.
AB  - European nations are compelled to reduce reliance on landfill as a destination
      for household waste, and should, in principle, achieve this goal with due
      recognition of the aims and principles of the waste hierarchy. Past research has
      predominantly focused on recycling, whilst interactions between changing waste
      destinies, causes and drivers of household waste management change, and potential
      consequences for the goal of the waste hierarchy are less well understood. This
      study analysed Local Authority Collected Waste (LACW) for England, at national,
      regional and sub-regional level, in terms of the destination of household waste
      to landfill, incineration and recycling. Information about waste partnerships,
      waste management infrastructure and collection systems was collected to help
      identify and explain changes in waste destinies. Since 1996, the proportion of
      waste landfilled in England has decreased, in tandem with increases in recycling
      and incineration. At the regional and sub-regional (Local Authority; LA) level,
      there have been large variations in the relative proportions of waste landfilled,
      incinerated and recycled or composted. Annual increases in the proportion of
      household waste incinerated were typically larger than increases in the
      proportion recycled. The observed changes took place in the context of legal and
      financial drivers, and the circumstances of individual LAs (e.g. landfill
      capacity) also explained the changes seen. Where observed, shifts from landfill
      towards incineration constitute an approach whereby waste management moves up the
      waste hierarchy as opposed to an attempt to reach the most preferred option(s);
      in terms of resource efficiency, this practice is sub-optimal. The requirement to
      supply incinerators with a feedstock over their lifespan reduces the benefits of
      developing of recycling and waste reduction, although access to incineration
      infrastructure permits short-term and marked decreases in the proportion of LACW
      landfilled. We conclude that there is a need for clearer national strategy and co
      ordination to inform and guide policy, practice, planning and investment in
      infrastructure such that waste management can be better aligned with the
      principles of the circular economy and resource efficiency. If the ongoing stand
      off between national political figures and the waste sector continues, England's
      waste policy remains destined for indecision. 

PMID- 25771763
TI  - Waste paper for recycling: Overview and identification of potentially critical
      substances.
AB  - Paper product manufacturing involves a variety of chemicals used either directly
      in paper and pulp production or in the conversion processes (i.e. printing,
      gluing) that follow. Due to economic and environmental initiatives, paper
      recycling rates continue to rise. In Europe, recycling has increased by nearly
      20% within the last decade or so, reaching a level of almost 72% in 2012. With
      increasing recycling rates, lower quality paper fractions may be included. This
      may potentially lead to accumulation or un-intended spreading of chemical
      substances contained in paper, e.g. by introducing chemicals contained in waste
      paper into the recycling loop. This study provides an overview of chemicals
      potentially present in paper and applies a sequential hazard screening procedure
      based on the intrinsic hazard, physical-chemical and biodegradability
      characteristics of the substances. Based on the results, 51 substances were
      identified as potentially critical (selected mineral oils, phthalates, phenols,
      parabens, as well as other groups of chemicals) in relation to paper recycling.
      It is recommended that these substances receive more attention in waste paper. 

PMID- 25771764
TI  - Does IARS2 deficiency cause an intrinsic disorder of bone development (skeletal
      dysplasia) or are the reported skeletal changes secondary to growth hormone
      deficiency and neuromuscular involvement?

PMID- 25771765
TI  - Response to: does IARS2 deficiency cause an intrinsic disorder of bone
      development (skeletal dysplasia) or are the reported skeletal changes secondary
      to growth hormone deficiency and neuromuscular involvement?

PMID- 25771769
TI  - Etiologies of Sarcoidosis.
AB  - Since sarcoidosis was first described more than a century ago, the etiologic
      determinants causing this disease remain uncertain. Studies suggest that genetic,
      host immunologic, and environmental factors interact together to cause
      sarcoidosis. Immunologic characteristics of sarcoidosis include non-caseating
      granulomas, enhanced local expression of T helper-1 (and often Th17) cytokines
      and chemokines, dysfunctional regulatory T-cell responses, dysregulated Toll-like
      receptor signaling, and oligoclonal expansion of CD4+ T cells consistent with
      chronic antigenic stimulation. Multiple environmental agents have been suggested
      to cause sarcoidosis. Studies from several groups implicate mycobacterial or
      propionibacterial organisms in the etiology of sarcoidosis based on tissue
      analyses and immunologic responses in sarcoidosis patients. Despite these
      studies, there is no consensus on the nature of a microbial pathogenesis of
      sarcoidosis. Some groups postulate sarcoidosis is caused by an active viable
      replicating infection while other groups contend there is no clinical,
      pathologic, or microbiologic evidence for such a pathogenic mechanism. The
      authors posit a novel hypothesis that proposes that sarcoidosis is triggered by a
      hyperimmune Th1 response to pathogenic microbial and tissue antigens associated
      with the aberrant aggregation of serum amyloid A within granulomas, which
      promotes progressive chronic granulomatous inflammation in the absence of ongoing
      infection. 

PMID- 25771777
TI  - Blind vaginal fetal fibronectin swab for prediction of preterm birth.
AB  - AIM: To assess the accuracy of blind vaginal swab in diagnosis of preterm labor
      (PTL) and prediction of subsequent occurrence of preterm birth (PTB). METHODS:
      Eligible women who presented at 24-34 weeks of gestation with threatened PTL had
      their cervicovaginal secretions sequentially sampled for fetal fibronectin (fFN)
      using two types of swabbing techniques. The first swab was a blind vaginal swab
      collected without the aid of speculum, while the second one was a routine
      cervicovaginal swab. All participants were followed up until delivery. RESULTS:
      fFN in both swabs was significantly higher in women who delivered before term
      compared with women who delivered at term. On regression analysis, r(2) = 0.735
      and 0.785 for blind vaginal and cervicovaginal swabs respectively, while on
      receiver operating characteristic analysis the area under curve was 0.965 and
      0.977, respectively, without a statistically significant difference. Using an fFN
      cut-off of >=0.05 MUg/dL, the sensitivity, specificity, positive predictive value
      and negative predictive value of blind vaginal swab to predict PTB were 53.9%,
      91.9%, 70.0% and 85.0%, respectively; while those for cervicovaginal swab were
      58.3%, 94.7%, 77.8% and 87.8%, respectively. CONCLUSIONS: In women presenting at
      24-34 weeks of gestation with threatened PTL, blind vaginal fFN swab is as
      effective as cervicovaginal swab to predict PTB, but it is easier to perform and
      does not require doctor supervision.

PMID- 25771770
TI  - Animal models of primary biliary cirrhosis.
AB  - Primary biliary cirrhosis (PBC) is characterized histologically by the presence
      of chronic non-suppurative destructive cholangitis of the small interlobular bile
      duct, leading to chronic progressive cholestasis. Most PBC patients are
      asymptomatic and have a reasonable prognosis, but a few develop esophageal
      varices or jaundice, rapidly leading to liver failure within a short period. As
      multiple factors appear to be involved in the onset of PBC, its clinical course
      may be complicated. Therefore, the use of an animal model would be valuable for
      clarifying the pathogenesis of PBC. Here, we review recent data of selected PBC
      models, particularly spontaneous models, xenobiotic immunized models, and
      infection-triggered models. There are a number of spontaneous models: the
      NOD.c3c4, dominant-negative TGF-beta receptor II, IL-2Ralpha-/-, Scurfy, and
      Ae2a,b-/- mice. These animal models manifest distinct clinical and immunological
      features similar, but also often different, from those of human PBC. It is clear
      that a combination of genetic predisposition, environmental factors, and
      immunological dysfunction contribute to the pathogenesis of PBC. The diverse
      clinical course and complexity of the immunological mechanisms of PBC cannot be
      fully recapitulated solely any single animal model. The challenge remains to
      develop a progressive PBC disease model that exhibits fibrosis, and ultimately
      hepatic failure. 

PMID- 25771778
TI  - Comparison of the capacity of two biotic ligand models to predict chronic copper
      toxicity to two Daphnia magna clones and formulation of a generalized
      bioavailability model.
AB  - Although it is increasingly recognized that biotic ligand models (BLMs) are
      valuable in the risk assessment of metals in aquatic systems, the use of 2
      differently structured and parameterized BLMs (1 in the United States and another
      in the European Union) to obtain bioavailability-based chronic water quality
      criteria for copper is worthy of further investigation. In the present study, the
      authors evaluated the predictive capacity of these 2 BLMs for a large dataset of
      chronic copper toxicity data with 2 Daphnia magna clones, termed K6 and ARO. One
      BLM performed best with clone K6 data, whereas the other performed best with
      clone ARO data. In addition, there was an important difference between the 2 BLMs
      in how they predicted the bioavailability of copper as a function of pH. These
      modeling results suggested that the effect of pH on chronic copper toxicity is
      different between the 2 clones considered, which was confirmed with additional
      chronic toxicity experiments. Finally, because fundamental differences in model
      structure between the 2 BLMs made it impossible to create an average BLM, a
      generalized bioavailability model (gBAM) was developed. Of the 3 gBAMs developed,
      the authors recommend the use of model gBAM-C(uni), which combines a log-linear
      relation between the 21-d median effective concentration (expressed as free
      Cu(2+) ion activity) and pH, with more conventional BLM-type competition
      constants for sodium, calcium, and magnesium. This model can be considered a
      first step in further improving the accuracy of chronic toxicity predictions of
      copper as a function of water chemistry (for a variety of Daphnia magna clones),
      even beyond the robustness of the current BLMs used in regulatory applications.

PMID- 25771779
TI  - Changes in selected subpopulations of lymphocytes in dogs infected with Babesia
      canis treated with imidocarb.
AB  - OBJECTIVE: The purpose of this study was to track changes in selected
      subpopulations of lymphocytes in the blood of dogs infected with Babesia (B.)
      canis and treated with imidocarb. MATERIAL AND METHODS: The study included 16
      dogs divided into two groups. The first group (n = 6) consisted of healthy
      control animals. Dogs of the se- cond group (n = 10) were infected with B. canis
      and after establishment of the diagnosis each animal received a single dose of
      imido- carb (5 mg/kg). Flow cytometry was used to enumerate several immune cell
      phenotypes. RESULTS: It was concluded that the invasion of B. canis contributes
      to the decreased percentage of CD3+, CD4+, CD8+, CD21+ lymphocytes in the blood
      of infected animals. The decreased level of tested subpopulations of lymphocytes
      in group 2 persisted for the entire 12-day period of the test. After the
      administration of imidocarb, each tested lymphocyte fraction in the blood of the
      dogs with babesiosis increased, but did not reach physiological values.
      CONCLUSION: The presented results indicate that the resolution of clinical signs
      associated with babesiosis may be related to the stimulation and intensity of
      cellular immunity, dependent on the CD4+ T cells profile. After administration of
      imidocarb, the parasitemia is cleared which allows the recovery of the lymphocyte
      populations.

PMID- 25771780
TI  - A "no-touch-technique" in mandibular reconstruction with reconstruction plate and
      free flap transfer.
AB  - OBJECTIVE: Mandibular reconstruction with a mandibular reconstruction plate (MRP)
      and free flap transfer can involve serious plate-related complications. The aim
      of our study is to present our new "no-touch-technique" which keeps an MRP not
      contaminated to saliva during the entire operation for the reduction of plate
      related complications. PATIENTS AND METHODS: Data were retrospectively collected
      on 29 patients who had undergone segmental mandibulectomy for head and neck tumor
      and mandibular reconstruction with an MRP and free flap transfer from 2004 to
      2013; 12 patients were reconstructed with our no-touch-technique from 2010 to
      2013 (no-touch-technique group), and 17 patients with the conventional technique
      from 2004 to 2009 (conventional group). A rectus abdominis musculocutaneous flap
      or anterolateral thigh flap was transferred in all patients. The rates of
      perioperative recipient site complications including total flap necrosis, partial
      flap necrosis, wound infection, fistula formation and wound dehiscence, and
      reoperation for complications were compared between the groups. RESULTS: All
      flaps were successfully transferred although one venous thrombosis formation
      occurred in the conventional group. The rate of wound infection in the no-touch
      technique group (8.3%) was significantly lower than that in the conventional
      group (47.1%) (P = 0.04). Additionally, the rate of fistula formation in the no
      touch-technique group (8.3%) tended to be lower than that in the conventional
      group (29.4%) (P = 0.35). CONCLUSION: The results of our study showed that our no
      touch-technique may be a safe and effective procedure for the prevention of
      perioperative plate-related complications for mandibular reconstruction with an
      MRP and free flap transfer.

PMID- 25771781
TI  - Computerized methodology for micro-CT and histological data inflation using an
      IVUS based translation map.
AB  - A framework for the inflation of micro-CT and histology data using intravascular
      ultrasound (IVUS) images, is presented. The proposed methodology consists of
      three steps. In the first step the micro-CT/histological images are manually co
      registered with IVUS by experts using fiducial points as landmarks. In the second
      step the lumen of both the micro-CT/histological images and IVUS images are
      automatically segmented. Finally, in the third step the micro-CT/histological
      images are inflated by applying a transformation method on each image. The
      transformation method is based on the IVUS and micro-CT/histological contour
      difference. In order to validate the proposed image inflation methodology, plaque
      areas in the inflated micro-CT and histological images are compared with the ones
      in the IVUS images. The proposed methodology for inflating micro-CT/histological
      images increases the sensitivity of plaque area matching between the inflated and
      the IVUS images (7% and 22% in histological and micro-CT images, respectively). 

PMID- 25771782
TI  - Fractional 1,550 nm Ytterbium/Erbium fiber laser in the treatment of lichen
      amyloidosis: clinical and histological study.
AB  - BACKGROUND AND OBJECTIVE: Lichen amyloidosis is characterized by amyloid
      deposition in the papillary dermis, presenting clinically with intensely pruritic
      hyperkeratotic papules. Various treatment modalities have been used but the
      results are generally unsatisfactory. Several studies show that non-ablative
      fractional lasers can be used to treat depositional diseases due to their
      capability of inducing transepidermal elimination of the dermal content. To
      investigate the efficacy and safety of a non-ablative fractional 1,550 nm
      Yttrium/Erbium fiber laser for the treatment of lichen amyloidosis. MATERIALS AND
      METHODS: Ten subjects with a clinical and histological diagnosis of lichen
      amyloidosis were treated with fractional non-ablative laser using a 7-cm tip,
      with the parameter of 30 mJ/cm2 and 1,000 microscopic treatment zones (MTZ)/cm2
      for three sessions at 4-week intervals. Clinical improvement (in terms of global
      improvement score, brownish/hyperpigmentation, thickness, and number of papules)
      was evaluated using a quartile grading scale at baseline, and 4, 12, and 24 weeks
      after the last treatment. Itch score and subjective satisfaction rates were also
      assessed. Adverse events were recorded, and pain was scored using a visual analog
      scale (VAS). Histologic changes were observed using standard staining with
      hematoxylin and eosin, as well as special stains of alkaline congo red and
      crystal violet at baseline and 4 weeks after treatment. RESULTS: At 4 and 24
      weeks after treatment, the lichen amyloid lesions had statistically significantly
      improved in all aspects compared to baseline (P = 0.01 and P = 0.016,
      respectively; Wilcoxon signed-rank test). However, partial recurrence was
      reported in 2 out of 10 subjects. All subjects rated itching symptom
      significantly improved after only the first treatment (P < 0.05). Minimal side
      effects were recorded, including a burning sensation, transient erythema, and
      edema. Histological evaluation demonstrated decreased epidermal thickness, and
      degeneration and shrinkage of amyloid material deposition in the papillary
      dermis. There was no amyloid material deposition noted in two out of eight
      histopathology studies. CONCLUSIONS: The non-ablative fractional 1,550 nm
      Ytterbium/Erbium fiber laser is safe and effective for the treatment of lichen
      amyloidosis. However, larger controlled studies are required to further establish
      the efficacy of this treatment.

PMID- 25771783
TI  - Do No Evil: Unnoticed Assumptions in Accounts of Conscience Protection.
AB  - In this paper, I argue that distinctions between traditional and contemporary
      accounts of conscience protections, such as the account offered by Aulisio and
      Arora, fail. These accounts fail because they require an impoverished conception
      of our moral lives. This failure is due to unnoticed assumptions about the
      distinction between the traditional and contemporary articulations of conscience
      protection. My argument proceeds as follows: First, I highlight crucial
      assumptions in Aulisio and Arora's argument. Next, I argue that respecting
      maximal play in values, though a fine goal in our liberal democratic society,
      raises a key issue in exactly the situations that matter in these cases. Finally,
      I argue that too much weight is given to a too narrow conception of values. There
      are differences between appeals to conscience that are appropriately categorized
      as traditional or contemporary, and a way to make sense of conscience in the
      contemporary medical landscape is needed. However, the normative implications
      drawn by Aulisio and Arora do not follow from this distinction without much
      further argument. I conclude that their paper is a helpful illustration the
      complexity of this issue and of a common view about conscience, but insofar as
      their view fails to account for the richness of our moral life, they fail to
      resolve the issue at hand.

PMID- 25771784
TI  - Psychological Determinants of Whole-Body Endurance Performance.
AB  - BACKGROUND: No literature reviews have systematically identified and evaluated
      research on the psychological determinants of endurance performance, and sport
      psychology performance enhancement guidelines for endurance sports are not
      founded on a systematic appraisal of endurance-specific research. OBJECTIVE: A
      systematic literature review was conducted to identify practical psychological
      interventions that improve endurance performance and to identify additional
      psychological factors that affect endurance performance. Additional objectives
      were to evaluate the research practices of the included studies, to suggest
      theoretical and applied implications, and to guide future research. METHODS:
      Electronic databases, forward-citation searches and manual searches of reference
      lists were used to locate relevant studies. Peer-reviewed studies were included
      when they chose an experimental or quasi-experimental research design; a
      psychological manipulation; endurance performance as the dependent variable; and
      athletes or physically active, healthy adults as participants. RESULTS:
      Consistent support was found for using imagery, self-talk and goal setting to
      improve endurance performance, but it is unclear whether learning multiple
      psychological skills is more beneficial than learning one psychological skill.
      The results also demonstrated that mental fatigue undermines endurance
      performance, and verbal encouragement and head-to-head competition can have a
      beneficial effect. Interventions that influenced perception of effort
      consistently affected endurance performance. CONCLUSIONS: Psychological skills
      training could benefit an endurance athlete. Researchers are encouraged to
      compare different practical psychological interventions, to examine the effects
      of these interventions for athletes in competition and to include a placebo
      control condition or an alternative control treatment. Researchers are also
      encouraged to explore additional psychological factors that could have a negative
      effect on endurance performance. Future research should include psychological
      mediating variables and moderating variables. Implications for theoretical
      explanations for endurance performance and evidence-based practice are described.

PMID- 25771786
TI  - Non-metal single/dual doped carbon quantum dots: a general flame synthetic method
      and electro-catalytic properties.
AB  - A combustion flame method is developed for the convenient and scalable
      fabrication of single- and dual-doped carbon quantum dots (CQDs) (N-CQDs, B-CQDs,
      P-CQDs, and S-CQDs and dual-doped B,N-CQDs, P,N-CQDs, and S,N-CQDs), and the
      doping contents can be easily adjusted by simply changing the concentrations of
      precursors in ethanol. These single/dual-doped CQDs, especially B,N-CQDs, show
      high catalytic activities for the oxygen reduction reaction. 

PMID- 25771785
TI  - The impact of high-intensity interval training versus moderate-intensity
      continuous training on vascular function: a systematic review and meta-analysis.
AB  - BACKGROUND: Vascular dysfunction is a precursor to the atherosclerotic cascade,
      significantly increasing susceptibility to cardiovascular events such as
      myocardial infarction or stroke. Previous studies have revealed a strong
      relationship between vascular function and cardiorespiratory fitness (CRF). Thus,
      since high-intensity interval training (HIIT) is a potent method of improving
      CRF, several small randomized trials have investigated the impact on vascular
      function of HIIT relative to moderate-intensity continuous training (MICT).
      OBJECTIVE: The aim of this study was to systematically review the evidence and
      quantify the impact on vascular function of HIIT compared with MICT. METHODS:
      Three electronic databases (PubMed, Embase, and MEDLINE) were searched (until May
      2014) for randomized trials comparing the effect of at least 2 weeks of HIIT and
      MICT on vascular function. HIIT protocols involved predominantly aerobic exercise
      at a high intensity, interspersed with active or passive recovery periods. We
      performed a meta-analysis to compare the mean difference in the change in
      vascular function assessed via brachial artery flow-mediated dilation (FMD) from
      baseline to post-intervention between HIIT and MICT. The impact of HIIT versus
      MICT on CRF, traditional cardiovascular disease (CVD) risk factors, and
      biomarkers associated with vascular function (oxidative stress, inflammation, and
      insulin resistance) was also reviewed across included studies. RESULTS: Seven
      randomized trials, including 182 patients, met the eligibility criteria and were
      included in the meta-analysis. A commonly used HIIT prescription was four
      intervals of 4 min (4 * 4 HIIT) at 85-95% of maximum or peak heart rate
      (HRmax/peak), interspersed with 3 min of active recovery at 60-70% HRmax/peak,
      three times per week for 12-16 weeks. Brachial artery FMD improved by 4.31 and
      2.15% following HIIT and MICT, respectively. This resulted in a significant (p <
      0.05) mean difference of 2.26%. HIIT also had a greater tendency than MICT to
      induce positive effects on secondary outcome measures, including CRF, traditional
      CVD risk factors, oxidative stress, inflammation, and insulin sensitivity.
      CONCLUSION: HIIT is more effective at improving brachial artery vascular function
      than MICT, perhaps due to its tendency to positively influence CRF, traditional
      CVD risk factors, oxidative stress, inflammation, and insulin sensitivity.
      However, the variability in the secondary outcome measures, coupled with the
      small sample sizes in these studies, limits this finding. Nonetheless, this
      review suggests that 4 * 4 HIIT, three times per week for at least 12 weeks, is a
      powerful form of exercise to enhance vascular function.

PMID- 25771787
TI  - TiS3 transistors with tailored morphology and electrical properties.
AB  - Control over the morphology of TiS3 is demonstrated by synthesizing 1D
      nanoribbons and 2D nanosheets. The nanosheets can be exfoliated down to a single
      layer. Through extensive characterization of the two morphologies, differences in
      the electronic properties are found and attributed to a higher density of sulphur
      vacancies in nanosheets, which, according to density functional theory
      calculations, leads to an n-type doping. 

PMID- 25771788
TI  - No infections in 1300 anterior cruciate ligament reconstructions with vancomycin
      pre-soaking of hamstring grafts.
AB  - PURPOSE: To investigate the pre-soaking of hamstring grafts in topical
      vancomycin, in addition to IV prophylaxis, during anterior cruciate ligament
      (ACL) reconstruction to reduce the incidence of post-operative infection, and to
      describe an evidence-based diagnostic and treatment algorithm to facilitate early
      diagnosis and appropriate management of possible knee sepsis post-operatively
      after ACL reconstruction. METHODS: This study is a controlled observational
      series comprising of 1585 individuals who underwent ACL reconstruction over a 13
      year period. All surgeries were performed by a single surgeon at the same
      hospital. Group 1 consisted of 285 patients who received pre-operative IV
      antibiotics without topical graft pre-soaking. Group 2 consisted of 1300
      individuals who received IV antibiotics and graft pre-soaking in a vancomycin
      solution of 5 mg/mL. RESULTS: In group 1, a total of four patients suffered a
      post-operative joint infection (1.4 %). Three out of the four were culture
      positive for Staphylococcus species. The fourth was culture negative but was
      managed as an acute infection. Group 2 suffered no post-operative infections (0
      %). Statistical analysis of the vancomycin pre-soak with IV antibiotics group,
      compared with IV antibiotics-alone group, revealed a significantly reduced post
      operative infection rate using a Fisher's exact test (P = 0.0011) and Chi-square
      test with Yates' correction (P = 0.0003). CONCLUSIONS: Pre-soaking of hamstrings
      grafts with topical vancomycin reduced the rate of post-operative infection when
      compared to IV antibiotics alone. This technique should be utilised by surgeons
      to reduce the overall incidence of knee sepsis post-ACL reconstruction. LEVEL OF
      EVIDENCE: III.

PMID- 25771789
TI  - Control of paradoxical kinematics in posterior cruciate-retaining total knee
      arthroplasty by increasing posterior femoral offset.
AB  - PURPOSE: Balancing the posterior cruciate ligament (PCL) with posterior cruciate
      retaining total knee replacement (PCR-TKR) aims to restore femoral rollback. In
      practice, paradoxical roll forward persists. The purpose of this study is to
      propose a technique for optimizing PCL tension. Because PCL function starts above
      60 degrees  of flexion, we hypothesize that PCL balancing requires flexion gap
      tightening by oversizing the femoral component and increasing posterior condylar
      offset (PCO). METHODS: PCR-TKR was performed in 21 osteoarthritis patients with a
      gap-balancing technique. The femoral component was oversized if more than a 5-mm
      posterior drawer existed after tibial component implantation. Kinematics was
      recorded intra-operatively in two steps with dedicated navigation software
      (Praxim, La Tronche, Isere, France): antero-posterior (AP) displacements of
      condylo-tibial contact points were observed in native and implanted knees, with
      each knee serving as its own control. The absence of paradoxical displacements
      was verified once the final implants were inserted. RESULTS: Paradoxical medial
      condyle displacement (11 mm) persisted in a single case. On average, posterior
      displacement of the medial condyle decreased from 9 +/- 9 to 1 +/- 6 mm (p =
      0.001) and that of the lateral condyle from 16 +/- 14 to 6 +/- 6 mm (p = 0.006).
      In the 0 degrees -30 degrees  flexion interval, posterior displacement was 2
      times less than before implantation for the medial condyle (p = 0.001), and 4
      times less for the lateral condyle (p = 0.004). The course of the lateral condyle
      decreased from 2 +/- 3 to 0 +/- 4 mm in the 90 degrees -120 degrees  flexion
      interval (p = 0.046). Six-month flexion was 124 degrees  +/- 17 degrees .
      CONCLUSION: Femoral component oversizing allows us to control paradoxical forward
      displacements in 95 % of cases. When balancing PCR prostheses, AP laxity should
      be taken into account. Increasing PCO appears to be a reliable technique for
      adjusting PCL balance. Thus, it may optimize extensor mechanism action and,
      subsequently, the functional results of PCR-TKR. LEVEL OF EVIDENCE: Diagnostic
      study, Level II.

PMID- 25771790
TI  - Combination chemotherapy of doxorubicin, all-trans retinoic acid and low
      molecular weight heparin based on self-assembled multi-functional polymeric
      nanoparticles.
AB  - Based on the complementary effects of doxorubicin (DOX), all-trans retinoic acid
      (ATRA) and low molecular weight heparin (LMWH), the combination therapy of DOX,
      ATRA and LMWH was expected to exert the enhanced anti-tumor effects and reduce
      the side effects. In this study, amphiphilic LMWH-ATRA conjugate was synthesized
      for encapsulating the DOX. In this way, DOX, ATRA and LMWH were assembled into a
      single nano-system by both chemical and physical modes to obtain a novel anti
      tumor targeting drug delivery system that can realize the simultaneous delivery
      of multiple drugs with different properties to the tumor. LMWH-ATRA nanoparticles
      exhibited good loading capacities for DOX with excellent physico-chemical
      properties, good biocompatibility, and good differentiation-inducing activity and
      antiangiogenic activity. The drug-loading capacity was up to 18.7% with an
      entrapment efficiency of 78.8%. It was also found that DOX-loaded LMWH-ATRA
      nanoparticles (DHR nanoparticles) could be efficiently taken up by tumor cells
      via endocytic pathway, and mainly distributed in cytoplasm at first, then
      transferred into cell nucleus. Cell viability assays suggested that DHR
      nanoparticles maintained the cytotoxicity effect of DOX on MCF-7 cells. Moreover,
      the in vivo imaging analysis indicated that DiR-loaded LMWH-ATRA nanoparticles
      could target the tumor more effectively as compared to free DiR. Furthermore, DHR
      nanoparticles possessed much higher anticancer activity and reduced side effects
      compared to free drugs solution. These results suggested that DHR nanoparticles
      could be considered as a promising targeted delivery system for combination
      cancer chemotherapy with lower adverse effects. 

PMID- 25771791
TI  - Autophagy receptor NDP52 regulates pathogen-containing autophagosome maturation.
AB  - Xenophagy, an essential anti-microbial cell-autonomous mechanism, relies on the
      ability of the autophagic process to selectively entrap intracellular pathogens
      within autophagosomes to degrade them in autolysosomes. This selective targeting
      is carried out by specialized autophagy receptors, such as NDP52, but it is
      unknown whether the fusion of pathogen-containing autophagosomes with lysosomes
      is also regulated by pathogen-specific cellular factors. Here, we show that NDP52
      also promotes the maturation of autophagosomes via its interaction with LC3A,
      LC3B, and/or GABARAPL2 through a distinct LC3-interacting region, and with MYOSIN
      VI. During Salmonella Typhimurium infection, the regulatory function of NDP52 in
      autophagosome maturation is complementary but independent of its function in
      pathogen targeting to autophagosomes, which relies on the interaction with LC3C.
      Thus, complete xenophagy is selectively regulated by a single autophagy receptor,
      which initially orchestrates bacteria targeting to autophagosomes and
      subsequently ensures pathogen degradation by regulating pathogen-containing
      autophagosome maturation.

PMID- 25771792
TI  - Pathogenic fungi regulate immunity by inducing neutrophilic myeloid-derived
      suppressor cells.
AB  - Despite continuous contact with fungi, immunocompetent individuals rarely develop
      pro-inflammatory antifungal immune responses. The underlying tolerogenic
      mechanisms are incompletely understood. Using both mouse models and human
      patients, we show that infection with the human pathogenic fungi Aspergillus
      fumigatus and Candida albicans induces a distinct subset of neutrophilic myeloid
      derived suppressor cells (MDSCs), which functionally suppress T and NK cell
      responses. Mechanistically, pathogenic fungi induce neutrophilic MDSCs through
      the pattern recognition receptor Dectin-1 and its downstream adaptor protein
      CARD9. Fungal MDSC induction is further dependent on pathways downstream of
      Dectin-1 signaling, notably reactive oxygen species (ROS) generation as well as
      caspase-8 activity and interleukin-1 (IL-1) production. Additionally, exogenous
      IL-1beta induces MDSCs to comparable levels observed during C. albicans
      infection. Adoptive transfer and survival experiments show that MDSCs are
      protective during invasive C. albicans infection, but not A. fumigatus infection.
      These studies define an innate immune mechanism by which pathogenic fungi
      regulate host defense.

PMID- 25771795
TI  - Erratum to: Usefulness of Clinical Signs and Diagnostic Tests for Suspected Leaks
      in Bariatric Surgery.

PMID- 25771793
TI  - Gastro-intestinal Quality of Life After Metabolic Surgery for the Treatment of
      Type 2 Diabetes Mellitus.
AB  - BACKGROUND: Emerging evidence has shown that bariatric/metabolic surgery
      ameliorates type 2 diabetes (T2DM) in mildly obese patients (BMI < 35 kg/m(2))
      but long-term data is inadequate. We investigated the change of the quality of
      life after metabolic surgery in not well-controlled T2DM patients with BMI < 35
      kg/m(2). METHODS: The quality of life was measured by the gastrointestinal
      quality of life index (GIQLI), a 36-item questionnaire divided into three domains
      of general health and one domain of specific gastro-intestinal symptoms,
      administered before operation, at 3, 6, and 12 months after surgery. A control
      group matched in age, gender, and BMI was recruited for comparison. RESULTS: A
      total of 86 patients were enrolled, and the preoperative BMI and HbA1C (mean +/-
      SD) were 30.7 +/- 2.8 kg/m(2) and 9.3 +/- 2.1 %, respectively. At 1 year after
      surgery, the BMI and HbA1C were 24.3 +/- 2.3 kg/m(2) and 6.2 +/- 1.1 %,
      respectively. There was a significantly improvement in all of the measures of
      glucose metabolism. Complete remission (HbA1C < 6.0 %) was achieved in 56
      subjects (65 %) at 12 months. The GIQLI score was significantly impaired in T2DM
      patients before surgery compared with the control group. The GIQLI score
      significantly increased from 109.2 +/- 20.0 to 116.1 +/- 14.2 points 1 year after
      surgery. The patients had improvement in the three domains of general health
      (social, physical, and emotional function) without a difference with the normal
      control but deteriorated in the domain of specific symptoms. Most of the patients
      experienced symptoms including abdominal pain, bloating, flatulence, belching,
      abdominal noise, regurgitation, dysphagia, slow eating speed, nausea, bowel
      urgency, and incontinence after metabolic syndrome. CONCLUSIONS: Health-related
      QOL improved dramatically after metabolic surgery for not well-controlled T2DM
      patients with BMI < 35 kg/m(2), but patients might develop specific gastro
      intestinal symptoms after surgery.

PMID- 25771794
TI  - abiliti Closed-Loop Gastric Electrical Stimulation System for Treatment of
      Obesity: Clinical Results with a 27-Month Follow-Up.
AB  - BACKGROUND: The aim of the study was to evaluate the safety and effectiveness of
      a novel closed-loop gastric electric stimulation device (abiliti system)
      featuring a transgastric sensor to detect food intake and an accelerometer to
      record physical activity to induce and maintain lifestyle changes to treat
      obesity. METHODS: In a prospective, multi-center study, 34 obese subjects (BMI of
      42.1 +/- 5.3 kg/m(2)) who passed an eligibility evaluation were implanted with
      the abiliti system. Safety evaluation included an endoscopic exam to assess the
      intragastric electrode healing. Efficacy evaluation at 1 year of therapy included
      weight loss, improvements in eating, and exercise behavior and quality of life.
      RESULTS: The transgastric implant controlled by endoscopy was stable for all
      participants. At 12 months (12 M) the mean excess weight loss (EWL) was 28.7%
      (95%CI, 34.5 to 22.5%), and mean reduction in BMI was 4.8 +/- 3.2 kg/m(2). At 27
      months (27 M), the EWL was 27.5% (95% CI, 21.3% to 33.7%). Eating behavior,
      evaluated by the "Three Factor Eating Questionnaire", showed a significant
      increase in the cognition factor and decrease in the disinhibition and hunger
      factors at 12 M in comparison to baseline (p < 0.001). Participants significantly
      increased their weekly physical activity (p < 0.001). Quality of life was
      improved in 55.2% of the patients. CONCLUSIONS: Gastric electrical stimulation
      with abiliti system in obese participants is well tolerated and leads to
      significant 12 M weight loss, which was stable to 27 M. We suggest that weight
      loss is achieved due to the assessed alteration of eating behavior in particular
      the reduction in disinhibition and hunger, and the measured increase in physical
      activity.

PMID- 25771796
TI  - Ovarian cancer survival by tumor dominance, a surrogate for site of origin.
AB  - OBJECTIVES: Recent studies suggest that a proportion of ovarian tumors may
      actually originate in the distal fallopian tube. The objective of this study was
      to examine the relationship between dominance (a surrogate for site of origin)
      and survival, following a diagnosis of epithelial ovarian cancer. METHODS: We
      classified 1,386 tumors as dominant (putatively originating in the ovary) and non
      dominant (putatively originating in the fallopian tube), using parameters
      obtained from pathology reports. Dominant tumors were restricted to one ovary or
      one involved ovary that exceeded the other in dimension by at least twofold,
      while non-dominant tumors were identified as having a greater likelihood of a
      tubal origin if the disease was equally distributed across the ovaries. Cox
      proportional hazards models were used to estimate the hazard ratios (HRs) and 95%
      confidence intervals (CIs) associated with dominance. RESULTS: Non-dominant
      tumors were more likely to be serous, stage III/IV, and be associated with a
      BRCA1/2 mutation, increasing parity and use of estrogen hormone replacement
      therapy (p <= 0.01). In contrast, 46 and 26% of the dominant tumors were serous
      and endometrioid, respectively, with a more even distribution of stage (p <
      0.0001). Women with a non-dominant tumor had an increased risk of death compared
      to women with a dominant tumor (multivariate HR 1.28; 95% CI 1.02-1.60). Findings
      were similar in our analysis restricted to serous only subtypes (HR 1.28; 95% CI
      1.01-1.63). CONCLUSION: These preliminary findings suggest significantly worse
      survival among women diagnosed with a tumor putatively arising from fallopian
      tube.

PMID- 25771797
TI  - The impact of obesity on prostate cancer recurrence observed after exclusion of
      diabetics.
AB  - PURPOSE: Although overall there is a positive association between obesity and
      risk of prostate cancer (PrCa) recurrence, results of individual studies are
      somewhat inconsistent. We investigated whether the failure to exclude diabetics
      in prior studies could have increased the likelihood of conflicting results.
      METHODS: A total of 610 PrCa patients who underwent radical prostatectomy between
      2005 and 2012 were followed for recurrence, defined as a rise in serum PSA >= 0.2
      ng/ml following surgery. Body mass index (BMI) and history of type 2 diabetes
      were documented prior to PrCa surgery. The analysis was conducted using Cox
      proportional hazard models. RESULTS: Obesity (25.6 %) and diabetes (18.7 %) were
      common in this cohort. There were 87 (14.3 %) recurrence events during a median
      follow-up of 30.8 months after surgery among the 610 patients. When analyzed
      among all PrCa patients, no association was observed between BMI/obesity and PrCa
      recurrence. However, when analysis was limited to non-diabetics, obese men had a
      2.27-fold increased risk (95 % CI 1.17-4.41) of PrCa recurrence relative to
      normal weight men, after adjusting for age and clinical/pathological tumor
      characteristics. CONCLUSIONS: This study found a greater than twofold association
      between obesity/BMI and PrCa recurrence in non-diabetics. We anticipated these
      results because the relationship between BMI/obesity and the biologic factors
      that may underlie the PrCa recurrence-BMI/obesity association, such as insulin,
      may be altered by the use of anti-diabetes medication or diminished beta-cell
      insulin production in advanced diabetes. Studies to further assess the molecular
      factors that explain the BMI/obesity-PrCa recurrence relationship are warranted.

PMID- 25771798
TI  - Evaluation of Phenolic Antioxidant Capacity in Grains of Modern and Old Durum
      Wheat Genotypes by the Novel QUENCHERABTS Approach.
AB  - The QUENCHERABTS (QUick, Easy, New, CHEap and Reproducible) approach for
      antioxidant capacity (AC) determination is based on the direct reaction of 2,2'
      azino-bis-(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) radical cation with
      fine solid food particles. So, it may resemble the antioxidant action in foods or
      in human gastrointestinal trait. Here, the QUENCHER approach was used to study AC
      of durum wheat (Triticum durum Desf.) grains. Firstly, it was assessed which kind
      of antioxidants determines QUENCHER response. This has been performed by
      comparing AC measured by QUENCHERABTS and that measured by classical TEACABTS
      (Trolox equivalent antioxidant capacity) in four different extracts from whole
      flour of 10 durum wheat varieties containing: lipophilic, hydrophilic, insoluble
      bound phenolic (IBP) and free-soluble phenolic (FSP) compounds. QUENCHERABTS data
      were unrelated to AC of water-extractable antioxidants and weakly correlated (r =
      0.405, P < 0.05) to AC of the lipophilic ones; on the contrary, QUENCHERABTS
      response was mainly related to AC of IBP (r = 0.907, P < 0.001) and to a lesser
      extent of FSP extracts (r = 0.747, P < 0.001). Consistently, correlation was also
      found with the phenolic content of IBP and FSP (r = 0.760, P < 0.001 and r =
      0.522, P < 0.01, respectively), thus confirming that QUENCHERABTS assay mainly
      assesses AC due to IBP. So, this assay was used in a first screening study to
      compare AC of bioactive IBP of thirty-six genotypes/landraces covering a century
      of cultivation in Italy. Interestingly, no relevant AC difference between modern
      and old genotypes was found, thus suggesting that a century of plant breeding did
      not decrease phenol-dependent health potential in durum wheat.

PMID- 25771799
TI  - Increased brain bio-distribution and chemical stability and decreased
      immunogenicity of an engineered variant of GDNF.
AB  - Several lines of evidence indicate that Glial cell line-derived neurotrophic
      factor (GDNF) is a trophic factor for dopaminergic neurons. Direct parenchymal
      administration of GDNF is robustly neuroprotective and neurorestorative in
      multiple neurotoxin-based animal models (rat and non-human primate (NHP)) of
      Parkinson's Disease (PD), suggesting its potential as a therapeutic agent.
      Although small, open-label clinical trials of intra-putamenal administration of
      bacteria-derived, full length, wild type GDNF (GDNFwt) were efficacious in
      improving standardized behavioral scores, a double-blinded, randomized controlled
      trial failed to do so. We hypothesize that the lack of clinical efficacy of
      GDNFwt in the larger randomized trial was due to poor bio-distribution in the
      putamen and/or poor chemical stability while in the delivery device for prolonged
      time periods at 37 degrees C. The development of neutralizing antibodies in some
      patients may also have been a contributing factor. GDNFv is an engineered form of
      GDNFwt, expressed and purified from mammalian cells, designed to overcome these
      limitations, including removal of the N-terminal heparin-binding domain to
      improve its diffusivity in brain parenchyma by reducing its binding to
      extracellular matrix (ECM), and key amino acid substitutions to improve chemical
      stability. Intra-striatal administration of a single injection of GDNFv in the
      rat produced significantly greater brain distribution than GDNFwt, consistent
      with reduced binding to ECM. Using liquid chromatography/mass spectrometry
      (LS/MS) methods GDNFv was shown to have improved chemical stability compared to
      GDNFwt when stored at 37 degrees C for 4weeks. In addition, GDNFv resulted in
      lower predicted clinical immunogenicity compared to GDNFwt, as demonstrated by
      reduced CD4+ T cell proliferation and reduced IL-2-induced secretion in
      peripheral blood mononucleated cells collected from volunteers representing the
      world's major histocompatibility complex (MHC) haplotypes. GDNFv was demonstrated
      to be pharmacologically equivalent to GDNFwt in the key parameters in vitro of
      GFRalpha1 receptor binding, c-Ret phosphorylation, neurite outgrowth, and in vivo
      in its ability to increase dopamine turnover (DA). GDNFv protected dopamine nerve
      terminals and neurons in a 6-hydroxy-dopamine (6-OHDA) rat model. In summary, we
      empirically demonstrate the superior properties of GDNFv compared to GDNFwt
      through enhanced bio-distribution and chemical stability concurrently with
      decreased predicted clinical immunogenicity while maintaining pharmacological and
      neurotrophic activity. These data indicate that GDNFv is an improved version of
      GDNF suitable for clinical assessment as a targeted regenerative therapy for PD. 

PMID- 25771801
TI  - Diffuse and persistent blood-spinal cord barrier disruption after contusive
      spinal cord injury rapidly recovers following intravenous infusion of bone marrow
      mesenchymal stem cells.
AB  - Intravenous infusion of mesenchymal stem cells (MSCs) has been shown to reduce
      the severity of experimental spinal cord injury (SCI), but mechanisms are not
      fully understood. One important consequence of SCI is damage to the
      microvasculature and disruption of the blood spinal cord barrier (BSCB). In the
      present study we induced a contusive SCI at T9 in the rat and studied the effects
      of intravenous MSC infusion on BSCB permeability, microvascular architecture and
      locomotor recovery over a 10week period. Intravenously delivered MSCs could not
      be identified in the spinal cord, but distributed primarily to the lungs where
      they survived for a couple of days. Spatial and temporal changes in BSCB
      integrity were assessed by intravenous infusions of Evans blue (EvB) with in vivo
      and ex vivo optical imaging and spectrophotometric quantitation of EvB leakage
      into the parenchyma. SCI resulted in prolonged BSCB leakage that was most severe
      at the impact site but disseminated extensively rostral and caudal to the lesion
      over 6weeks. Contused spinal cords also showed an increase in vessel size,
      reduced vessel number, dissociation of pericytes from microvessels and decreases
      in von Willebrand factor (vWF) and endothelial barrier antigen (EBA) expression.
      In MSC-treated rats, BSCB leakage was reduced, vWF expression was increased and
      locomotor function improved beginning 1 week post-MSC infusion, i.e., 2weeks post
      SCI. These results suggest that intravenously delivered MSCs have important
      effects on reducing BSCB leakage which could contribute to their therapeutic
      efficacy. 

PMID- 25771800
TI  - Dietary supplementation with omega-3 polyunsaturated fatty acids robustly
      promotes neurovascular restorative dynamics and improves neurological functions
      after stroke.
AB  - Stroke is a devastating neurological disease with no satisfactory therapies to
      preserve long-term neurological function, perhaps due to the sole emphasis on
      neuronal survival in most preclinical studies. Recent studies have revealed the
      importance of protecting multiple cell types in the injured brain, such as
      oligodendrocytes and components of the neurovascular unit, before long-lasting
      recovery of function can be achieved. For example, revascularization in the
      ischemic penumbra is critical to provide various neurotrophic factors that
      enhance the survival and activity of neurons and other progenitor cells, such as
      oligodendrocyte precursor cells. In the present study, we hypothesized that
      chronic dietary supplementation with fish oil promotes post-stroke angiogenesis,
      neurogenesis, and oligodendrogenesis, thereby leading to long-term functional
      improvements. Mice received dietary supplementation with n-3 PUFA-enriched fish
      oil for three months before and up to one month after stroke. As expected,
      dietary n-3 PUFAs significantly increased levels of n-3 PUFAs in the brain and
      improved long-term behavioral outcomes after cerebral ischemia. n-3 PUFAs also
      robustly improved revascularization and angiogenesis and boosted the survival of
      NeuN/BrdU labeled newborn neurons up to 35days after stroke injury. Furthermore,
      these pro-neurogenic effects were accompanied by robust oligodendrogenesis. Thus,
      this is the first study to demonstrate that chronic dietary intake of n-3 PUFAs
      is an effective prophylactic measure not only to protect against ischemic injury
      for the long term but also to actively promote neurovascular restorative dynamics
      and brain repair. 

PMID- 25771802
TI  - Patients with left ventricular ejection fraction greater than 58 % have fewer
      incidences of future acute decompensated heart failure admission and all-cause
      mortality.
AB  - Based on our previous observation, inertia stress (IS) of late systolic aortic
      flow was often observed in left ventricles with relatively higher left
      ventricular (LV) ejection fraction (EF). Most left ventricles with relatively
      lower LVEF did not have IS. Accordingly, lack of IS may correlate with LV
      diastolic dysfunction through the loss of LV elastic recoil and may contribute to
      the pathogenesis of heart failure (HF) and reduced survival. We enrolled 144
      consecutive patients that underwent cardiac catheterization for the diagnosis of
      coronary artery disease. Left ventricular ejection fraction (LVEF) was obtained
      from left ventriculography. The IS was calculated from the LV pressure (P)-dP/dt
      relation. The study endpoint of this retrospective outcome-observational study
      was combined subsequent acute decompensated heart failure (ADHF) and all-cause
      mortality. During the follow-up period (median 6.1 years), seven unscheduled
      hospitalizations for ADHF and nine all-cause deaths were observed. The event-free
      survival rate was significantly higher among patients with IS than among patients
      without IS (log-rank, p = 0.001). On a multivariate Cox regression analysis, lack
      of IS was a prime predictor of the endpoint during follow-up (hazard ratio: 6.98;
      95 % confidence interval: 1.48-33.03; p = 0.01). An LVEF >= 58 % was a surrogate
      indicator for the presence of IS, and patients with LVEF >= 58 % had fewer
      incidences of the endpoint than patients with LVEF < 58 %. In conclusion, lack of
      IS or LVEF < 58 % should be a predictor of future ADHF and all-cause mortality. 

PMID- 25771803
TI  - Adrenal insufficiency causes life-threatening arrhythmia with prolongation of QT
      interval.
AB  - A 63-year-old woman who had hypopituitarism was re-admitted to our hospital
      because of fever, diarrhea and disturbance of consciousness with life-threatening
      arrhythmia due to prolongation of the QT interval. She has been treated with
      hydrocortisone consequently, and has shown few ventricular arrhythmias with
      normalization of the QT interval. There have been several reports showing the
      case of prolonged QT interval with adrenal insufficiency, but there are few
      reports of isolated adrenocorticotropic hormone deficiency without any
      electrolytes imbalance that showed polymorphic ventricular tachycardia associated
      with QT prolongation. We discuss some possible mechanisms of how adrenal
      insufficiency causes life-threatening arrhythmia. Since lack of glucocorticoid
      hormone might induce prolongation of the QT interval, patients with adrenal
      insufficiency should be paid attention as candidates of lethal arrhythmias
      particularly when exposed to excessive stresses. 

PMID- 25771805
TI  - 50-plus years of fungal viruses.
AB  - Mycoviruses are widespread in all major taxa of fungi. They are transmitted
      intracellularly during cell division, sporogenesis, and/or cell-to-cell fusion
      (hyphal anastomosis), and thus their life cycles generally lack an extracellular
      phase. Their natural host ranges are limited to individuals within the same or
      closely related vegetative compatibility groups, although recent advances have
      established expanded experimental host ranges for some mycoviruses. Most known
      mycoviruses have dsRNA genomes packaged in isometric particles, but an increasing
      number of positive- or negative-strand ssRNA and ssDNA viruses have been isolated
      and characterized. Although many mycoviruses do not have marked effects on their
      hosts, those that reduce the virulence of their phytopathogenic fungal hosts are
      of considerable interest for development of novel biocontrol strategies.
      Mycoviruses that infect endophytic fungi and those that encode killer toxins are
      also of special interest. Structural analyses of mycoviruses have promoted better
      understanding of virus assembly, function, and evolution. 

PMID- 25771807
TI  - A molecular pulley based on a triply interlocked [2]rotaxane.
AB  - A novel triply interlocked [2]rotaxane based on a triptycene-derived tris(crown
      ether) host and a guest embedded with three dibenzylammonium and three N
      methyltriazolium recognition sites was designed and synthesized, which showed
      pulley-like shuttling motion controlled by acid and base. 

PMID- 25771804
TI  - Timing is everything: Fine-tuned molecular machines orchestrate paramyxovirus
      entry.
AB  - The Paramyxoviridae include some of the great and ubiquitous disease-causing
      viruses of humans and animals. In most paramyxoviruses, two viral membrane
      glycoproteins, fusion protein (F) and receptor binding protein (HN, H or G)
      mediate a concerted process of recognition of host cell surface molecules
      followed by fusion of viral and cellular membranes, resulting in viral
      nucleocapsid entry into the cytoplasm. The interactions between the F and HN, H
      or G viral glycoproteins and host molecules are critical in determining host
      range, virulence and spread of these viruses. Recently, atomic structures,
      together with biochemical and biophysical studies, have provided major insights
      into how these two viral glycoproteins successfully interact with host receptors
      on cellular membranes and initiate the membrane fusion process to gain entry into
      cells. These studies highlight the conserved core mechanisms of paramyxovirus
      entry that provide the fundamental basis for rational anti-viral drug design and
      vaccine development. 

PMID- 25771808
TI  - Emission behaviors of unsymmetrical 1,3-diaryl-beta-diketones: a model perfectly
      disclosing the effect of molecular conformation on luminescence of organic
      solids.
AB  - A series of unsymmetrical 1,3-diaryl-beta-diketones 1-6 displaying molecular
      conformation-dependent fluorescence quantum yields have been synthesized.
      Crystals with planar molecular conformation such as 1, 2, 3 and 4 are highly
      fluorescent (phif: 39-53%), and the one holding slightly twisted conformation (5)
      is moderately luminescent (phif = 17%), while crystal 6 possessing heavily bent
      structure is completely nonluminous (phif ~ 0). The distinct fluorescence
      efficiencies are ascribed to their different molecular conformations, since all
      the crystals hold the same crystal system, space group and crystal packing
      structures. Additionally, the fluorescent crystals 1-5 display low threshold
      amplified spontaneous emission (ASE) with small full widths at half-maximum
      (FWHM: 3-7 nm), indicating their potential as candidates for organic crystal
      lasing devices.

PMID- 25771809
TI  - A start codon CMT1X mutation associated with transient encephalomyelitis causes
      complete loss of Cx32.
AB  - X-linked Charcot-Marie-Tooth disease (CMTX1) results from numerous mutations in
      the GJB1 gene encoding the gap junction protein connexin32 (Cx32) and is one of
      the commonest forms of inherited neuropathy. Owing to the expression of Cx32 not
      only in Schwann cells but also in oligodendrocytes, a subset of CMT1X patients
      develops central nervous system (CNS) clinical manifestations in addition to
      peripheral neuropathy. While most GJB1 mutations appear to cause peripheral
      neuropathy through loss of Cx32 function, the cellular mechanisms underlying the
      CNS manifestations remain controversial. A novel start codon GJB1 mutation
      (p.Met1Ile) has been found in a CMT1X patient presenting with recurrent episodes
      of transient encephalomyelitis without apparent signs of peripheral neuropathy.
      In order to clarify the functional consequences of this mutation, we examined the
      cellular expression of two different constructs cloned from genomic DNA including
      the mutated start codon. None of the cloned constructs resulted in detectable
      expression of Cx32 by immunocytochemistry or immunoblot, although mRNA was
      produced at normal levels. Furthermore, co-expression with the other major
      oligodendrocyte connexin, Cx47, had no negative effect on GJ formation by Cx47.
      Finally, lysosomal and proteasomal inhibition in cells expressing the start codon
      mutant constructs failed to recover any detection of Cx32 as a result of impaired
      protein degradation. Our results indicate that the Cx32 start codon mutation is
      equivalent to a complete loss of the protein with failure of translation,
      although transcription is not impaired. Thus, complete loss of Cx32 function is
      sufficient to produce CNS dysfunction with clinical manifestations. 

PMID- 25771810
TI  - Exhibition of the Bronsted acid-base character of a Schiff base in palladium(II)
      complex formation: lithium complexation, fluxional properties and catalysis of
      Suzuki reactions in water.
AB  - The reaction of the dialdehyde N,N-di(alpha-formylpyrrolyl-alpha-methyl)-N
      methylamine with two equiv. of 2,6-diisopropylaniline yielded two Schiff bases:
      bis(iminopyrrolylmethyl)amine () and its hydrolyzed monoimino compound () after
      column separation. The dimeric lithium complex [(HL)Li]2 () containing the
      monoanionic form of was obtained by treating with (n)BuLi. The presence of both
      proton donors and acceptors causes the diimino compound to undergo
      tautomerization to exhibit an amine-azafulvene structure, though the central
      amine nitrogen competes for a proton. As a result, in the presence of Pd(2+)
      ions, the cationic complex [Pd(Cl)(H2L)][Cl] () containing one pendant amine
      azafulvene arm and the protonated central amine nitrogen was obtained. Its X-ray
      structure showed that the bond distances are reversed for the imino-pyrrole
      moiety relative to those in the structure of . However, the reaction of with
      [Pd(OAc)2] afforded the neutral complex [PdL] () containing the dianionic form of
      the ligand. The reaction of with [PdCl2(PhCN)2] yielded a zwitterionic complex
      [PdCl2(H2L')] () owing to the presence of the central amine nitrogen. The
      formation of these palladium complexes with the features mentioned above can be
      explained by invoking the Bronsted acid-base character of the Schiff base.
      Complex is fluxional owing to the up and down movements of the palladium square
      plane formed by two 5-membered palladacycles, which causes the interconversion of
      its enantiomers and is studied by the variable temperature (1)H NMR method.
      Furthermore, both complexes and are precatalysts for the Suzuki-Miyaura cross
      coupling reaction in water. Sterically encumbered and electronically different
      substrates including activated aryl chlorides and benzyl halides gave the coupled
      products in very good yields. The reaction proceeds even at room temperature and
      in the presence of a large excess amount of mercury. 

PMID- 25771811
TI  - VPS35 and EIF4G1 interactions and novel candidate genes for PD: from genes to
      pathways and back.

PMID- 25771806
TI  - Origins and evolution of viruses of eukaryotes: The ultimate modularity.
AB  - Viruses and other selfish genetic elements are dominant entities in the
      biosphere, with respect to both physical abundance and genetic diversity. Various
      selfish elements parasitize on all cellular life forms. The relative abundances
      of different classes of viruses are dramatically different between prokaryotes
      and eukaryotes. In prokaryotes, the great majority of viruses possess double
      stranded (ds) DNA genomes, with a substantial minority of single-stranded (ss)
      DNA viruses and only limited presence of RNA viruses. In contrast, in eukaryotes,
      RNA viruses account for the majority of the virome diversity although ssDNA and
      dsDNA viruses are common as well. Phylogenomic analysis yields tangible clues for
      the origins of major classes of eukaryotic viruses and in particular their likely
      roots in prokaryotes. Specifically, the ancestral genome of positive-strand RNA
      viruses of eukaryotes might have been assembled de novo from genes derived from
      prokaryotic retroelements and bacteria although a primordial origin of this class
      of viruses cannot be ruled out. Different groups of double-stranded RNA viruses
      derive either from dsRNA bacteriophages or from positive-strand RNA viruses. The
      eukaryotic ssDNA viruses apparently evolved via a fusion of genes from
      prokaryotic rolling circle-replicating plasmids and positive-strand RNA viruses.
      Different families of eukaryotic dsDNA viruses appear to have originated from
      specific groups of bacteriophages on at least two independent occasions.
      Polintons, the largest known eukaryotic transposons, predicted to also form virus
      particles, most likely, were the evolutionary intermediates between bacterial
      tectiviruses and several groups of eukaryotic dsDNA viruses including the
      proposed order "Megavirales" that unites diverse families of large and giant
      viruses. Strikingly, evolution of all classes of eukaryotic viruses appears to
      have involved fusion between structural and replicative gene modules derived from
      different sources along with additional acquisitions of diverse genes. 

PMID- 25771812
TI  - A highly acid-resistant novel strain of Lactobacillus johnsonii No. 1088 has
      antibacterial activity, including that against Helicobacter pylori, and inhibits
      gastrin-mediated acid production in mice.
AB  - A novel strain of Lactobacillus johnsonii No. 1088 was isolated from the gastric
      juice of a healthy Japanese male volunteer, and characterized for its
      effectiveness in the stomach environment. Lactobacillus johnsonii No. 1088 was
      found to have the strongest acid resistance among several lactobacilli examined
      (>10% of cells survived at pH 1.0 after 2 h), and such a high acid resistance
      property was a specific characteristic of this strain of L. johnsonii. When
      cultured with various virulent bacteria, L. johnsonii No. 1088 inhibited the
      growth of Helicobacter pylori, Escherichia coli O-157, Salmonella Typhimurium,
      and Clostridium difficile, in which case its effectiveness was more potent than
      that of a type strain of L. johnsonii, JCM2012. In addition to its effect in
      vitro, L. johnsonii No. 1088 inhibited the growth of H. pylori in human
      intestinal microbiota-associated mice in both its live and lyophilized forms.
      Moreover, L. johnsonii No. 1088 suppressed gastric acid secretion in mice via
      decreasing the number of gastrin-positive cells in the stomach. These results
      taken together suggest that L. johnsonii No. 1088 is a unique lactobacillus
      having properties beneficial for supporting H. pylori eradication by triple
      therapy including the use of a proton pump inhibitor (PPI) and also for
      prophylaxis of gastroesophageal reflux disease possibly caused after H. pylori
      eradication as a side effect of PPI. 

PMID- 25771813
TI  - Breast-feeding patterns of ethnic groups in rural western China.
AB  - OBJECTIVE: To determine the breast-feeding pattern of four main ethnic groups
      (the Han, Uygur, Tibetan and Zhuang) living in rural western China. DESIGN: The
      study utilized a cross-sectional design. SETTING: Forty-five counties in ten
      provinces in western China in 2005. SUBJECTS: A sample of 11 783 children younger
      than 36 months old (8960 Han, 1281 Uygur, 792 Tibetan and 750 Zhuang) and their
      mothers were recruited using a stratified, multistage, cluster random sampling
      method. RESULTS: The rates of exclusive breast-feeding of children at 6 months of
      age in the Han, Uygur, Tibetan and Zhuang ethnic groups were 11.6 %, 0.8%, 4.4%
      and 13.8%, respectively. The rates of any breast-feeding for children at 24
      months of age were 8.5%, 25.7%, 3.0% and 4.3% in the four ethnic groups,
      respectively. After adjusting for related factors, Zhuang children had a higher
      odds ratio of exclusive breast-feeding to 6 months compared with Han children,
      whereas Uygur and Tibetan children had lower odds ratio (Zhuang: OR=1.291; 95% CI
      1.006, 1.657; Uugur: OR=0.062; 95% CI 0.032, 0.121; Tibetan: OR=0.323; 95% CI
      0.220, 0.475). Uygur children had a lower hazard ratio of discontinued breast
      feeding compared with Han children, whereas Tibetan children had a higher hazard
      ratio (Uygur: HR=0.368; 95% CI 0.333, 0.408; Tibetan: HR=1.366; 95% CI 1.244,
      1.500). CONCLUSIONS: The breast-feeding pattern differed among the Han, Uygur,
      Tibetan and Zhuang ethnic groups. The results suggest that health education
      regarding the benefits of breast-feeding is needed in rural western China.

PMID- 25771814
TI  - Failure of intravitreal bevacizumab in the treatment of choroidal metastasis.
AB  - BACKGROUND: Metastasis to choroid is the most common intraocular malignancy,
      arising most frequently from carcinoma of breast in women and lung in men. Recent
      case reports have described successful use of intravitreal bevacizumab to achieve
      local control of such tumours. MATERIALS AND METHODS: Five cases of choroidal
      metastases from varying primaries: breast, lung, and colon were treated with
      intravitreal bevacizumab, and tumour response observed and documented with serial
      photographs and B-scans. RESULTS: Four of the five tumours were seen to progress
      despite intravitreal bevacizumab treatment. CONCLUSIONS: Intravitreal bevacizumab
      as the primary treatment of choroidal metastases is not recommended and should
      not delay more effective alternative treatments.

PMID- 25771815
TI  - Gene-gene interaction of CFH, ARMS2, and ARMS2/HTRA1 on the risk of neovascular
      age-related macular degeneration and polypoidal choroidal vasculopathy in Chinese
      population.
AB  - PURPOSE: To evaluate the association and interaction of five single-nucleotide
      polymorphisms (SNPs) in three genes (CFH, ARMS2, and ARMS2/HTRA1) with
      neovascular age-related macular degeneration (nAMD) and polypoidal choroidal
      vasculopathy (PCV) in Chinese population. METHODS: A total of 300 nAMD and 300
      PCV patients and 301 normal subjects participated in the present study. The
      allelic variants of rs800292, rs2274700, rs3750847, rs3793917, and rs1065489 were
      determined by matrix-assisted laser desorption/ionization time-of-flight mass
      spectrometry (MALDI-TOF-MS). Gene-gene interactions were evaluated by the data
      mining approach multifactor-dimensionality reduction (MDR) method. RESULTS: The
      risk alleles of CFH rs800292, rs2274700, ARMS2 rs3057847, and ARMS2/HTRA1
      rs3793917 showed significant difference between nAMD or PCV patients and controls
      (all P<0.01). The homozygosity of risk alleles for rs800292, rs2274700,
      rs3750847, and rs3793917 were significantly different between nAMD patients and
      controls (all P<0.01), and predisposed to PCV patients (all P<0.01). After cross
      validation consistency (CVC) and permutation tests, the two-locus model
      rs2274700_rs3750847 has a balanced accuracy of 64.37% in predicting nAMD disease
      risk. The one-marker model, rs3750847, and two-locus model rs2274700_rs3750847
      has a balanced accuracy of 66.07% and 65.89% in predicting PCV disease risk,
      respectively. Furthermore, CFH rs1065489 did not show significant association
      with nAMD (P>0.01), but was strongly associated with PCV in Chinese patients
      (P<0.001). CONCLUSIONS: In this study, we found that the interaction of ARMS2 and
      ARMS2/HTRA1 is significantly associated with nAMD, and the interaction of CFH and
      ARMS2 is pronounced in PCV development in Chinese population.

PMID- 25771816
TI  - Bimodal in vivo imaging provides early assessment of stem-cell-based
      photoreceptor engraftment.
AB  - PURPOSE: Subretinal transplantation of stem-cell-derived photoreceptor precursor
      cells (PPCs) is a promising and innovative approach to treating a range of
      blinding diseases. However, common barriers to efficient preclinical
      transplantation comes in the form of suboptimal graft architecture, limited graft
      survival, and immune-rejection, each of which cannot be assessed using
      conventional in vivo imaging (i.e., rodent ophthalmoscopy). With the majority of
      PPCs reported to die within the first few weeks after transplantation,
      understanding the mechanisms of graft failure, and ultimately devising
      preventative methods, currently relies on lengthy end point histology. To address
      these limitations, we hypothesized that combining two imaging modalities, optical
      coherence tomography (OCT) and fluorescence confocal scanning laser
      ophthalmoscopy (fcSLO), could provide a more rapid and comprehensive view of PPC
      engraftment. METHODS: Human ESC-derived PPCs were transplanted into 15 retinal
      dystrophic rats that underwent bimodal imaging at 0, 8, and 15 days
      posttransplant. RESULTS: Bimodal imaging provided serial detection of graft:
      placement, architecture, and survival; each undetectable under ophthalmoscopy.
      Bimodal imaging determined graft placement to be either: subretinal (n=7),
      choroidal (n=4), or vitreal (n=4) indicating neural retinal perforation. Graft
      architecture was highly variable at the time of transplantation, with notable
      redistribution over time, while complete, or near complete, graft loss was
      observed in the majority of recipients after day 8. Of particular importance was
      detection of vitreal aggregates overlying the graft-possibly an indicator of host
      site inflammation and rejection. CONCLUSION: Early real-time feedback of
      engraftment has the potential to greatly increase efficiency of preclinical
      trials in cell-based retinal therapeutics.

PMID- 25771817
TI  - Clinical relevance of quantified fundus autofluorescence in diabetic macular
      oedema.
AB  - PURPOSE: To quantify the signal intensity of fundus autofluorescence (FAF) and
      evaluate its association with visual function and optical coherence tomography
      (OCT) findings in diabetic macular oedema (DMO). METHODS: We reviewed 103 eyes of
      78 patients with DMO and 30 eyes of 22 patients without DMO. FAF images were
      acquired using Heidelberg Retina Angiograph 2, and the signal levels of FAF in
      the individual subfields of the Early Treatment Diabetic Retinopathy Study grid
      were measured. We evaluated the association between quantified FAF and the logMAR
      VA and OCT findings. RESULTS: One hundred and three eyes with DMO had lower FAF
      signal intensity levels in the parafoveal subfields compared with 30 eyes without
      DMO. The autofluorescence intensity in the parafoveal subfields was associated
      negatively with logMAR VA and the retinal thickness in the corresponding
      subfields. The autofluorescence levels in the parafoveal subfield, except the
      nasal subfield, were lower in eyes with autofluorescent cystoid spaces in the
      corresponding subfield than in those without autofluorescent cystoid spaces. The
      autofluorescence level in the central subfield was related to foveal cystoid
      spaces but not logMAR VA or retinal thickness in the corresponding area.
      CONCLUSIONS: Quantified FAF in the parafovea has diagnostic significance and is
      clinically relevant in DMO.

PMID- 25771818
TI  - Endothelial cell loss and complication rates with combined Descemets stripping
      endothelial keratoplasty and cataract surgery in a UK centre.
AB  - PURPOSE: To report 6-month, 1- and 2-year endothelial cell loss (ECL), intra- and
      postoperative complications in a large series of patients undergoing either
      Descemets stripping endothelial keratoplasty (DSEK) or a combined
      phacoemulsification and DSEK in a UK centre. PATIENTS AND METHODS: Patients
      undergoing DSEK with or without concurrent cataract surgery were included in this
      retrospective study. Surgeries were performed between January 2006 and May 2013.
      Main outcomes included intra- and postoperative complications and percentage ECL.
      RESULTS: DSEK was performed in 226 eyes (210 patients). Of these, 141 eyes (126
      patients) underwent DSEK alone and 85 eyes (84 patients) underwent DSEK combined
      with cataract surgery. Excluding complex anterior segment pathology the mean
      percentage ECL at 6, 12 and 24 months was 40.5+/-13.4, 45.1+/-14.6 and 53.1+/
      13.0 in the DSEK group and 40.7+/-15.4, 42.6+/-15.3 and 49.6+/-16.5 in patients
      undergoing the combined procedure, respectively. There was no significant
      difference in percentage ECL at 6 or 24 months between the two groups both in
      complex and routine cases. Intraoperative complications occurred in four patients
      undergoing DSEK and three undergoing combined procedure. Postoperative
      complication rates did not reach statistical significance between the groups.
      CONCLUSION: Mean ECL and complication rates were comparable at 6, 12 and 24
      months in routine cases undergoing concurrent DSEK with cataract surgery and
      those undergoing DSEK. These data support the combined procedure in patients
      requiring both cataract surgery and endothelial keratoplasty. Further
      collaboration to report endothelial cell counts from other UK centres should be
      encouraged.

PMID- 25771819
TI  - Evaluation of corneal endothelial cell damage after vitreoretinal surgery:
      comparison of different endotamponades.
AB  - PURPOSE: We evaluated corneal endothelial cell (EC) damage after vitreoretinal
      surgery and compared the results using different tamponades. MATERIALS AND
      METHODS: This prospective controlled study included 45 eyes of 45 patients (24
      females, 21 males) who underwent pars plana vitrectomy with gas (sulphur
      hexafluoride, SF6, 20%) or silicone oil (SO) tamponade. Patients were assigned to
      one of the three groups: group 1 (phakic, 20% SF6 gas), group 2 (pseudophakic,
      20% SF6 gas), and group 3 (phakic, SO). Mean endothelial cell density (MCD), mean
      cell area (MCA), coefficient of variation in cell size (CV), and percentage of
      hexagonal cells (HC) values were measured using a non-contact specular microscope
      (SP-2000P; Topcon, Japan) at baseline and at 3 months after surgery. The fellow
      eye of each patient was used as a control. RESULTS: Group 2, which had the lowest
      baseline MCD and MCA values, was found to be different than groups 1 and 3
      (P=0.028 and 0.022, respectively). At 3 months postoperatively, all groups showed
      significantly lower MCD, HC and CV values than at baseline (all P<0.05). The mean
      changes in MCD at 3 months after surgery were 3.8+/-2.8% (mean+/-SD), 8.0+/-7.5%,
      and 4.6+/-5.4% in groups 1-3, respectively. The mean MCD changes in the fellow
      eyes were 0.31+/-1.41% in group 1, -0.63+/-1.90% in group 2, and 0.14+/-0.52 in
      group 3 at 3 months postoperatively (P>0.05 for all). CONCLUSIONS: Our findings
      revealed that corneal EC damage may occur after vitreoretinal surgery with gas or
      SO tamponade. Eyes that had undergone previous cataract surgery were more
      vulnerable to EC loss than phakic eyes, supporting the protective effect of an
      intact lens.

PMID- 25771820
TI  - The Daily Experiences of Adolescents in Lebanon With Sickle Cell Disease.
AB  - OBJECTIVES: Despite the psychosocial and physical consequences associated with
      sickle cell disease (SCD), the daily lived experience of adolescents diagnosed
      with this disease is a phenomenon rarely described. The objective of this study
      was to explore the daily lived experience of adolescents with SCD living in
      Lebanon. METHOD: Twelve adolescents with SCD between the ages of 12 and 17 years
      were interviewed with use of a semi-structured interview during a routine follow
      up visit after they were assessed as being pain free. Interviews were transcribed
      verbatim, and thematic analysis was conducted. RESULTS: Adolescents with SCD
      experience a layered burden consisting of physical, emotional, and sympathetic
      pain that affects much of their daily personal and social lives. Nevertheless,
      they seem to claim normalcy and to downplay their pain and suffering in order to
      limit their caregivers' distress. CONCLUSION: These findings can be used to
      assist health care providers in designing culturally sensitive interventions
      specifically designed for adolescents with SCD and their families to enable them
      to better cope with their illness.

PMID- 25771821
TI  - Enhanced sensitivity of double gate junctionless transistor architecture for
      biosensing applications.
AB  - In the present work, we demonstrate the potential of double gate junctionless
      (JL) architecture for enhanced sensitivity for detecting biomolecules in cavity
      modulated field effect transistors (FETs). The higher values of body factor,
      achieved in asymmetric gate operation under impact ionization is utilized for
      enhanced sensing margin which is nearly five times higher than compared to
      symmetrical mode operation. The intrinsic detection sensitivity is evaluated in
      terms of threshold voltage change, and the ratio of drain current in the presence
      and absence of biomolecules in JL nanotransistors. It is shown that asymmetric
      mode JL transistor achieves a higher degree of detection sensitivity even for a
      partially filled cavity. The work demonstrates the potential of JL channel
      architecture for cavity based dielectric modulated FET biosensors. 

PMID- 25771822
TI  - Case of early postoperative adhesion in a patient with molimina due to transverse
      vaginal septum concomitant with imperforate hymen.
AB  - Transverse vaginal septum is a residual vaginal plate composed of the Mullerian
      duct and urogenital sinus. Imperforate hymen results from failure of perforation
      of the membrane between the urogenital sinus and vaginal cavity. We report a rare
      case of concurrence of these two conditions. A 16-year-old girl had been treated
      with puncture several times for hematometra and hematocolpos from 13 years of age
      because of monthly occurrence of lower abdominal pain without menstrual bleeding
      and was referred to our hospital. Magnetic resonance imaging demonstrated
      hematometra, hematocolpos and expansion of the vaginal fornix. The imperforate
      hymen was incised and a slight adhesion at the lower vaginal cavity was detached.
      After that, a complete transverse vaginal septum, which was 5 mm thick, was
      identified. It was excised after ultrasonography-guided puncture. Although two
      cycles of menstrual bleeding took place, molimina recurred. Re-operation was
      performed 6 months after the first operation, and recurrence of adhesion in the
      lower vaginal cavity was identified. A silicon dilator was inserted, but she
      could not use it at home and instead used a tampon. Cyclic menstrual bleeding is
      observed 4 months after the second operation. 

PMID- 25771823
TI  - Ultra-high dispersion of graphene in polymer composite via solvent free
      fabrication and functionalization.
AB  - The drying process of graphene-polymer composites fabricated by solution
      processing for excellent dispersion is time consuming and suffers from a
      restacking problem. Here, we have developed an innovative method to fabricate
      polymer composites with well dispersed graphene particles in the matrix resin by
      using solvent free powder mixing and in-situ polymerization of a low viscosity
      oligomer resin. We also prepared composites filled with up to 20 wt% of graphene
      particles by the solvent free process while maintaining a high degree of
      dispersion. The electrical conductivity of the composite, one of the most
      significant properties affected by the dispersion, was consistent with the
      theoretically obtained effective electrical conductivity based on the mean field
      micromechanical analysis with the Mori-Tanaka model assuming ideal dispersion. It
      can be confirmed by looking at the statistical results of the filler-to-filler
      distance obtained from the digital processing of the fracture surface images that
      the various oxygenated functional groups of graphene oxide can help improve the
      dispersion of the filler and that the introduction of large phenyl groups to the
      graphene basal plane has a positive effect on the dispersion.

PMID- 25771824
TI  - Eosinophilic Coronary Periarteritis with Arterial Dissection: The Mast Cell
      Hypothesis.
AB  - A subset of coronary arterial dissections is associated with eosinophilic
      coronary periarteritis (ECPA); however, the pathogenesis of the process remains
      unclear. Mast cells normally reside in coronary arterial adventitia and are known
      mediators of eosinophilic inflammatory conditions such as type I hypersensitivity
      reactions. We report two cases in which coronary arterial dissection with ECPA
      was detected at autopsy. Tryptase, CD68, CD4, CD8, and CD1a immunohistochemical
      staining was performed to better characterize inflammation. While eosinophils
      represented a prominent periadventitial inflammatory cell, there were slightly
      more lymphocytes: CD4/CD8 ratios were within expected reference ranges. There
      were moderate numbers of macrophages, and few neutrophils or dendritic cells.
      Numbers of mast cells in dissected versus nondissected sections were compared:
      adventitial mast cell densities were threefold higher in dissected portions and
      showed a trend toward increased degranulation. These findings suggest that mast
      cells may play a role in orchestrating inflammation in cases of ECPA. 

PMID- 25771825
TI  - Minimizing immunosuppression as a trigger for a fatal antibody-mediated rejection
      after lung transplantation.

PMID- 25771826
TI  - Fluorescence intensity of composite layering combined with surface sealant
      submitted to staining solutions.
AB  - PURPOSE: The aim of this study was to evaluate the fluorescence intensity of a
      composite in different layering techniques combined to a surface sealant
      submitted to staining solutions. METHODS AND MATERIALS: One surface sealant and
      one composite resin (shades A2-0, A2, and YE) were tested. Specimens were carried
      out using layering with different shades of composite, and dental blocks
      (dentin/enamel) were obtained of human molars. Fluorescence intensity measurement
      performed using a spectrofluorophotometer, before and after storage in cola,
      orange juice, red wine, and distilled water. Data were subjected to analysis of
      variance and Fisher's test (alpha = 0.05). RESULTS: Initially, only A2-O + A2
      layering showed fluorescence intensity statistically similar to the natural
      tooth. Overall, groups sealed showed the highest fluorescence intensity compared
      with unsealed groups. The aging decreased the fluorescence intensity compared
      with initial values. Red wine showed the highest decrease on the fluorescence
      intensity. CONCLUSION: The fluorescence of composite restorations is dependent of
      the layering technique and is affected by the diet. CLINICAL SIGNIFICANCE: The
      staining solutions decreased the fluorescence intensity, even when the composite
      resins were sealed. Different shades of the same composite showed distinct
      fluorescence values, so there should be greater standardization of this property
      for tooth reconstruction success by the layering technique with large tissue
      loss.

PMID- 25771827
TI  - Trends in socio-economic inequalities in the Scottish diet: 2001-2009.
AB  - OBJECTIVE: To explore the association between diet and socio-economic position
      for 2007-2009 and investigate trends in socio-economic inequalities in the
      Scottish diet between 2001 and 2009. DESIGN: UK food purchase data (collected
      annually from 2001 to 2009) were used to estimate household-level consumption
      data. Population mean food consumption, nutrient intakes and energy density were
      estimated by quintiles of an area-based index of multiple deprivation. Food and
      nutrient intakes estimated were those targeted for change in Scotland and others
      indicative of diet quality. The slope and relative indices of inequality were
      used to assess trends in inequalities in consumption over time. SETTING:
      Scotland. SUBJECTS: Scottish households (n 5020). RESULTS: Daily consumption of
      fruit and vegetables (200 g, 348 g), brown/wholemeal bread (17 g, 26.5 g),
      breakfast cereals (16 g, 27 g) and oil-rich (21 g, 40 g) and white fish (77 g,
      112 g) were lowest, and that of total bread highest (105 g, 91.5 g) in the most
      deprived compared with the least deprived households, respectively, for the
      period 2007-2009. With regard to nutrients, there was no association between
      deprivation and the percentage of food energy from total fat and saturated fat;
      however, non-milk extrinsic sugar intakes (15.5%, 14.3%) and energy density (741
      kJ/100 g, 701 kJ/100 g) were significantly higher in the most deprived
      households. The slope and relative indices of inequality showed that inequalities
      in intakes between 2001 and 2009 have changed very little. CONCLUSIONS: There was
      no evidence to suggest that the difference in targeted food and nutrient intakes
      between the least and most deprived has decreased compared with previous years.

PMID- 25771828
TI  - Re: Neural injury after use of vasopressin and adrenaline during porcine
      cardiopulmonary resuscitation.

PMID- 25771829
TI  - When do plant radiations influence community assembly? The importance of
      historical contingency in the race for niche space.
AB  - Plant radiations are widespread but their influence on community assembly has
      rarely been investigated. Theory and some evidence suggest that radiations can
      allow lineages to monopolize niche space when founding species arrive early into
      new bioclimatic regions and exploit ecological opportunities. These early
      radiations may subsequently reduce niche availability and dampen diversification
      of later arrivals. We tested this hypothesis of time-dependent lineage
      diversification and community dominance using the alpine flora of New Zealand. We
      estimated ages of 16 genera from published phylogenies and determined their
      relative occurrence across climatic and physical gradients in the alpine zone. We
      used these data to reconstruct occupancy of environmental space through time,
      integrating palaeoclimatic and palaeogeological changes. Our analysis suggested
      that earlier-colonizing lineages encountered a greater availability of
      environmental space, which promoted greater species diversity and occupancy of
      niche space. Genera that occupied broader niches were subsequently more dominant
      in local communities. An earlier time of arrival also contributed to greater
      diversity independently of its influence in accessing niche space. We suggest
      that plant radiations influence community assembly when they arise early in the
      occupancy of environmental space, allowing them to exclude later-arriving
      colonists from ecological communities by niche preemption. 

PMID- 25771830
TI  - The crisis in the emergency medicine physician scientist workforce. In reply.

PMID- 25771831
TI  - Lactose-free milk for infants with acute gastroenteritis in a developing country:
      study protocol for a randomized controlled trial.
AB  - BACKGROUND: Acute gastroenteritis is a major cause of pediatric morbidity and
      mortality, accounting for 15% of all childhood deaths worldwide. In developing
      countries, diarrheal diseases continue to be a major public health burden.
      Evidence from developed countries suggests that intake of lactose-free milk
      during diarrheal episodes may reduce the duration of the illness in pediatric
      inpatients. It is unknown whether lactose-free milk reduces the severity or
      duration of acute gastroenteritis in infants treated in outpatient settings in
      developing countries where diarrhea is more severe, and results in higher
      morbidities and mortalities. We hypothesize that lactose-free milk intake during
      acute gastroenteritis would significantly decrease the duration and severity of
      diarrhea in infants presenting to the Emergency Department (ED), as compared with
      lactose-containing milk. METHODS/DESIGN: An open-label randomized clinical trial.
      STUDY POPULATION: 40 infants with acute gastroenteritis, age between 2 and 12
      months, presenting to the ED, will be randomized to control or intervention
      group. INTERVENTION: Lactose-free milk, whereas the control group will continue
      on regular infant formula for a total of 7 days. Infants will be followed up for
      7 days. OUTCOME MEASURES: Diarrhea duration, weight loss, illness clinic visits,
      hospitalization rate, parental satisfaction, and time to symptom resolution.
      STATISTICAL ANALYSIS: Descriptive and regression analysis will be conducted under
      the intention-to-treat basis by using SPSS version 21. DISCUSSION: Acute
      gastroenteritis is a public health burden for developing countries, with a
      significant impact on infant morbidity and mortality. Provision of infant formula
      that may reduce the duration and severity of diarrhea can decrease this burden in
      countries with limited healthcare resources, like Lebanon. The findings from this
      study are anticipated to provide evidence-based dietary recommendations for
      ambulatory infants with acute diarrhea in developing countries. TRIAL
      REGISTRATION: ClinicalTrials.gov NCT02246010; September 2014.

PMID- 25771832
TI  - Impact of comorbidities on the treatment of non-Hodgkin's lymphoma: a systematic
      review.
AB  - Treating non-Hodgkin's lymphoma in patients with comorbidities can be challenging
      because of possible interactions that may alter the treatment efficacy. We
      conducted a systematic review to determine the impact of comorbidities on various
      outcomes, evaluate the current data, and provide recommendations for future
      research. Twenty-one articles were selected. However, the study populations and
      design were greatly heterogeneous, and the quality of reporting was generally
      weak. The majority of studies demonstrated significant impact of comorbidity on
      survival, reporting poorer survival rates for patients with comorbidities
      compared to those with no comorbidities. However, the existing evidence is
      limited and of insufficient quality to establish solid conclusions and to guide
      treatment decisions. Prospective, well-designed studies are warranted. 

PMID- 25771833
TI  - Establishment of a counter-selectable markerless mutagenesis system in
      Veillonella atypica.
AB  - Using an alternative sigma factor ecf3 as target, we successfully established the
      first markerless mutagenesis system in the Veillonella genus. This system will be
      a valuable tool for mutagenesis of multiple genes for gene function analysis as
      well as for gene regulation studies in Veillonella. 

PMID- 25771834
TI  - An in situ antimicrobial susceptibility testing method based on in vivo
      measurements of chlorophyll alpha fluorescence.
AB  - Up to now antimicrobial susceptibility testing (AST) methods are indirect and
      generally involve the manual counting of bacterial colonies following the
      extraction of microorganisms from the surface under study and their inoculation
      in a separate procedure. In this work, an in situ, direct and instrumental method
      for the evaluation and assessment of antibacterial properties of materials and
      surfaces is proposed. Instead of indirectly determining antibacterial activity
      using the typical gram(-) test organisms with the subsequent manual colony count
      or inhibition zone measurement, the proposed procedure, employs photosynthetic
      gram(-) cyanobacteria deposited directly onto the surface under study and
      assesses cell proliferation and viability by a quick, accurate and reproducible
      instrumental chlorophyll fluorescence spectrophotometric technique. In contrast
      with existing methods of determination of antibacterial properties, it produces
      high resolution and quantitative results and is so versatile that it could be
      used to evaluate the antibacterial properties of any compound (organic,
      inorganic, natural or man-made) under any experimental conditions, depending on
      the targeted application. 

PMID- 25771835
TI  - A case of nasal glial heterotopia with complete excision.

PMID- 25771836
TI  - The Role of Id2 Protein in Neuroblatoma in Children.
AB  - Id (DNA binding and/or differentiation) proteins occur physiologically during
      ontogenesis and negatively regulate the activity of other helix-loop-helix (HLH)
      proteins. Id2 protein causes block of cells differentiation in the S phase of the
      cell cycle and regulates the activity of Rb protein. The role of Id2 protein in
      physiological cell cycle progression and in neuroblastoma (NBL) pathogenesis was
      proposed by Lasorella. The aim of the study was evaluation of Id2 expression and
      its prognostic significance in NBL cells coming from primary tumors and
      evaluation of its prognostic significance, and correlation of Id2 expression with
      known prognostic factors. Sixty patients with primary NBL treated from 1991 to
      2005 were included in the analysis. We found 50 patients with high and 10
      patients with low intensity of Id2 expression. The median percentage of NBL cells
      with Id2 expression was 88 %. We found no correlation between the number of NBL
      cells or the intensity of Id2 expression and OS and DFS. In patients with stage 4
      NBL, almost all patients had high expression of Id2 and it was significantly more
      common than in other disease stages (p = 0,03). We found no correlation between
      Id2 expression and other known prognostic factor in NBL patients. We assume that
      Id2 is not prognostic factor. However, due to its abundant expression in most of
      NBL cells and its role in cell cycle, it may be potential therapeutic target.
      Exact knowledge of expression time may be helpful in explaining mechanisms of
      oncogenesis.

PMID- 25771837
TI  - Dosimetric effect on pediatric conformal treatment plans using dynamic jaw with
      Tomotherapy HDA.
AB  - It is important to minimize the radiation dose delivered to healthy tissues in
      pediatric cancer treatment because of the risk of secondary malignancies.
      Tomotherapy HDA provides a dynamic jaw (DJ) delivery mode that creates a sharper
      penumbra at the craniocaudal ends of a target in addition to a fixed jaw (FJ)
      delivery mode. The purpose of this study was to evaluate its dosimetric effect on
      the pediatric cancer cases. We included 6 pediatric cases in this study. The dose
      profiles and plan statistics-target dose conformity, uniformity, organ-at-risk
      (OAR) mean dose, beam-on time, and integral dose-were compared for each case.
      Consequently, the target dose coverage and uniformity were similar for different
      jaw settings. The OAR dose sparing depended on its relative location to the
      target and disease sites. For example, in the head and neck cancer cases, the
      brain stem dose using DJ 2.5 was reduced by more than two-fold (2.4 Gy vs. 6.3
      Gy) than that obtained with FJ 2.5. The integral dose with DJ 2.5 decreased by
      more than 9% compared with that with FJ 2.5. Thus, using dynamic jaw in pediatric
      cases could be critical to reduce a probability of a secondary malignancy.

PMID- 25771838
TI  - N-acetyl-L-cysteine pre-treatment protects cryopreserved bovine spermatozoa from
      reactive oxygen species without compromising the in vitro developmental potential
      of intracytoplasmic sperm injection embryos.
AB  - Excess of reactive oxygen species (ROS) on in vitro embryo production systems
      negatively affects the quality and developmental potential of embryos, as result
      of a decreased sperm quality and increased DNA fragmentation. This issue is of
      major importance in assisted fertilisation procedures such as intracytoplasmic
      sperm injection (ICSI), because this technique does not allow the natural
      selection of competent spermatozoa, and therefore, DNA-damaged spermatozoa might
      be used to fertilise an egg. The aim of this study was to investigate a new
      strategy to prevent the potential deleterious effect of ROS on cryopreserved
      bovine spermatozoa. We evaluated the effect of a sperm pre-treatment with
      different concentrations of N-acetyl-L-cysteine (NAC) on ROS production,
      viability and DNA fragmentation and assessed the effect of this treatment on the
      in vitro developmental potential and quality of embryos generated by ICSI. The
      results show a strong scavenging effect of 1 and 10 mm NAC after exposure of
      spermatozoa to a ROS inducer, without compromising the viability and DNA
      integrity. Importantly, in vitro developmental potential and quality of embryos
      generated by ICSI with spermatozoa treated with NAC were not affected, confirming
      the feasibility of using this treatment before an ICSI cycle.

PMID- 25771839
TI  - Magnetic resonance imaging and laparoscopic management of an ovarian remnant in a
      bitch.
AB  - Ovarian remnant tissue was diagnosed in a 6-year-old female Pointer presented
      with a history of periodic signs of oestrus after ovariohysterectomy. The
      diagnosis was based on clinical gynaecological examination, vaginoscopy, vaginal
      cytology, analysis of serum progesterone concentration, and magnetic resonance
      imaging. The ovarian remnant tissue was approached in a minimally invasive manner
      via laparoscopy and resected with a vessel-sealing system. The oestrus signs
      disappeared within 14 days after laparoscopy. 

PMID- 25771840
TI  - The Effect of n-3 Fatty Acids on Small Dense Low-Density Lipoproteins in Patients
      With End-Stage Renal Disease: A Randomized Placebo-Controlled Intervention Study.
AB  - OBJECTIVE: Patients with end-stage renal disease (ESRD) have a high risk of
      cardiovascular disease. Small dense low-density lipoprotein (sdLDL) particles are
      particularly atherogenic. Marine n-3 polyunsaturated fatty acids (PUFA) may have
      a beneficial effect on numbers of sdLDL particles, and the aim of this study was
      to investigate the effect of n-3 PUFA on plasma levels of sdLDL in patients with
      ESRD. METHODS: ESRD patients with cardiovascular disease (n = 161) on chronic
      hemodialysis were randomized to treatment with 1.7 g of n-3 PUFA (n = 81) or 2 g
      of placebo (olive oil; n = 80) for 3 months. The study was double-blinded.
      Densities of LDL and percentages of sdLDL (sdLDL%) of total LDL were measured
      before and after intervention. On the basis of sdLDL%, patients were classified
      as having lipid pattern A, I (intermediate), or B defined by a successive
      increase in sdLDL concentration and decrease in lipid particle size. RESULTS: n-3
      PUFAs significantly reduced triglycerides. However, LDL cholesterol remained
      unchanged. In the n-3 group, the LDL density did not change significantly during
      follow-up. Similarly, the LDL density remained unchanged in the placebo group. In
      the n-3 group, the sdLDL% was 34% at baseline and unchanged at follow-up. At
      baseline 71% had LDL pattern A, 9% had pattern I, and 20% had pattern B, and none
      of these patterns were significantly changed by n-3 PUFA supplementation.
      CONCLUSION: Dietary supplementation with 1.7 g of n-3 PUFA had no effect on LDL
      density or sdLDL levels in patients with ESRD.

PMID- 25771841
TI  - Hearing preservation in vestibular schwannoma management.
AB  - OBJECTIVE: To compare hearing preservation between stereotactic radiotherapy
      (SRT) and conservative treatment of patients with unilateral vestibular
      schwannoma. DATA SOURCES: Retrospective case series comparing hearing outcomes of
      patients with a unilateral vestibular schwannoma managed conservatively or with
      stereotactic radiotherapy in a tertiary care academic centre. REVIEW METHODS: 
      PATIENTS: Tumor database patients with American Academy of Otolaryngology Head
      and Neck Surgery Class A or B hearing at the onset of study. Stereotactic
      radiotherapy patients were predominantly those who failed conservative
      management. INTERVENTIONS: Audiometric pure tone averages and speech
      discrimination scores as well as patient demographics, tumor location, size and
      growth were extracted. MAIN OUTCOME MEASURES: Hearing outcome measures were: 1)
      Hearing Preservation, i.e. no drop from Class A/B to Class C/D hearing, 2)
      Hearing Survival of Class A/B hearing in months, 3) Audiometric Pure Tone
      Averages, Difference between post-treatment and pre-treatment, and 4) Speech
      Discrimination Score Difference (pre-treatment-post treatment). Survival analysis
      and non-parametric tests were used for hearing outcome measures, with multiple
      covariates tested. RESULTS: Overall, serviceable hearing preservation among the
      123 patients was 51%. The median hearing survival time was 46 months (mean 59
      months). The Pure Tone averages and Speech Discrimination score differences were
      16 dB and 82% respectively over a median follow-up time of 43 months. No
      significant difference was found between the conservative and SRT groups in any
      hearing outcome. Class A patients showed far better hearing survival than Class B
      patients. CONCLUSIONS: No significant difference was demonstrated as to measures
      of hearing outcomes between stereotactic radiotherapy and conservative
      management. Excellent existing hearing appears to be the best predictor of long
      term hearing survival in the cohort studied.

PMID- 25771842
TI  - Meniere's disease: importance of socioeconomic and environmental factors.
AB  - STUDY OBJECTIVES: 1. Describe the prevalence of Meniere's disease in the United
      States. 2. Recognize important patient and environmental factors in Meniere's
      disease. METHODS: * Discharge data from the Nationwide Inpatient Sample, the
      largest US all-payer inpatient care database was analyzed for Meniere's disease
      between 2008 and 2010 in patients > 10 years old. Patient characteristics
      including prevalence, age, sex, race, household income, and geographic location
      were studied to determine any correlation with disease prevalence. * T-test, Chi
      square and logistic regression testing was used to compare the differences
      between groups for continuous and categorical data. RESULTS: * The lower limit of
      Meniere's prevalence in the United States population was 73 per 100,000, females
      84 per 100,000 compared to 56 per 100,000 among males (OR = 1.51, 95% CI 1.48
      1.54, P < 0.01). * Prevalence was highest in Caucasians 91 per 100,000, and was
      significantly higher than other ethnic groups (P < 0.05). * Prevalence increased
      as age with the highest prevalence found in 81-90 year age group. * Midwest
      prevalence (94 per 100,000) was significantly higher than other regions (P <
      0.001). * Meniere's is more common in less populated locations and the prevalence
      decreased as population increased. * Meniere's prevalence increased with
      household income. The highest prevalence was found among the 76th-100th quartile
      with rates of 86 per 100,000 for MD. CONCLUSIONS: Environmental factors, race and
      ethnicity, gender and age appear to be important factors in the prevalence of
      Meniere's disease.

PMID- 25771843
TI  - Delirium in fast-track colonic surgery.
AB  - BACKGROUND: Postoperative delirium (PD) is a common but serious problem after
      major surgery with a multifactorial pathogenesis including age, pain, opioid use,
      sleep disturbances and the surgical stress response. These factors have been
      minimised by the "fast-track methodology" previously demonstrated to enhance
      recovery and reduce morbidity. METHODS: Clinical symptoms of PD were routinely
      collected three times daily from preoperatively until discharge in a well-defined
      enhanced recovery program after colonic surgery in 247 consecutive patients.
      RESULTS: Total median length of hospital stay was 3 days. Seven patients (2.8%)
      developed clinical signs of PD most within the first 72 postoperative hours and
      only 1 patient with PD extending to 120 h postoperatively. Only 1 PD patient
      required treatment with serenase. PD patients were older (83 vs. 73 years) and
      had longer median stay (6 vs. 3 days). No difference in development of PD between
      open and laparoscopic operation could be demonstrated. Among the 7 patients with
      PD, 3 of these patients had later surgical complications. One patient had a
      subsequent strangulated small intestine, another an anastomotic leakage
      complicated by a bleeding gastric ulcer and death on day 12 and 1 with fever,
      abdominal pain and suspected but disproven anastomotic leakage (stay 21, 12 and
      22 days, respectively). The remaining 4 PD patients stayed 4, 4, 5 and 6 days
      with an uncomplicated course. CONCLUSIONS: These data support that an enhanced
      postoperative recovery program may decrease the risk and duration of PD after
      colonic surgery.

PMID- 25771844
TI  - Label-free detection of DNA using a light-addressable potentiometric sensor
      modified with a positively charged polyelectrolyte layer.
AB  - A multi-spot (16 spots) light-addressable potentiometric sensor (MLAPS)
      consisting of an Al-p-Si-SiO2 structure modified with a weak polyelectrolyte
      layer of PAH (poly(allylamine hydrochloride)) was applied for the label-free
      electrical detection of DNA (deoxyribonucleic acid) immobilization and
      hybridization by the intrinsic molecular charge for the first time. To achieve a
      preferentially flat orientation of DNA strands and thus, to reduce the distance
      between the DNA charge and MLAPS surface, the negatively charged probe single
      stranded DNAs (ssDNA) were electrostatically adsorbed onto the positively charged
      PAH layer using a simple layer-by-layer (LbL) technique. In this way, more DNA
      charge can be positioned within the Debye length, yielding a higher sensor
      signal. The surface potential changes in each spot induced due to the surface
      modification steps (PAH adsorption, probe ssDNA immobilization, hybridization
      with complementary target DNA (cDNA), non-specific adsorption of mismatched
      ssDNA) were determined from the shifts of photocurrent-voltage curves along the
      voltage axis. A high sensor signal of 83 mV was registered after immobilization
      of probe ssDNA onto the PAH layer. The hybridization signal increases from 5 mV
      to 32 mV with increasing the concentration of cDNA from 0.1 nM to 5 MUM. In
      contrast, a small signal of 5 mV was recorded in the case of non-specific
      adsorption of fully mismatched ssDNA (5 MUM). The obtained results demonstrate
      the potential of the MLAPS in combination with the simple and rapid LbL
      immobilization technique as a promising platform for the future development of
      multi-spot light-addressable label-free DNA chips with direct electrical readout.

PMID- 25771845
TI  - Timing of maxillofacial-oral injuries in an individual of the ancient city of
      Herculaneum (79 AD, Naples, Italy): a case report.
AB  - BACKGROUND: This study is based on the skeletal remains of an adult female from
      the ancient city of Herculaneum (Naples, Italy), who was a victim of the eruption
      of the nearby Vesuvius Volcano on 24-25 August, AD 79. RESULTS AND DISCUSSION:
      Examination of the maxillofacial region revealed evidence of unilateral condylar
      fracture and dislocation, as well as traumatic dental injuries. The injuries
      observed might have been the consequence of a direct blow to the mental region
      that was transmitted in a direction that raised the mandible, causing an indirect
      fracture in the right condylar neck when the condylar head collided directly with
      the temporal glenoid fossa. This indirect impact also resulted in partial
      fracture of three dental crowns due to the violent impact of the arches between
      them, and the sharp impact together of the upper and lower teeth. It is suggested
      that these injuries were sustained due to an accidental fall when the individual
      was between 7 and 15 years old, which is supported by the morphology, location
      and extension of the injuries, and the characterization of the impact.
      CONCLUSION: These results are an illustration of how dental anthropology and
      forensic approaches can be applied with great benefit to archaeological skeletal
      remains.

PMID- 25771846
TI  - The effect of enalapril on furosemide-activated renin-angiotensin-aldosterone
      system in healthy dogs.
AB  - Studies in our laboratory have revealed that furosemide-induced RAAS activation,
      evaluated via the urine aldosterone-to-creatinine ratio (UAldo:C), was not
      attenuated by the coadministration of benazepril, while enalapril successfully
      suppressed amlodipine-induced urinary aldosterone excretion. This study was
      designed to evaluate the efficacy of enalapril in suppressing ACE activity and
      furosemide-induced circulating RAAS activation. Failure to do so would suggest
      that this failure may be a drug class effect. We hypothesized that enalapril
      would suppress ACE activity and furosemide-induced circulating RAAS activation.
      Sixteen healthy hound dogs. The effect of furosemide (2 mg/kg PO, q12 h; Group F)
      and furosemide plus enalapril (0.5 mg/kg PO, q12 h; Group FE) on circulating RAAS
      was determined by plasma ACE activity, 4-6 h post-treatment, and urinary A:C on
      days -1, -2, 1, 4, and 7. There was a significant increase in the average urine
      aldosterone-to-creatinine ratio (UAldo:C) after administration of furosemide (P <
      0.05). Enalapril inhibited ACE activity (P < 0.0001) but did not significantly
      reduce aldosterone excretion. A significant (P < 0.05) increase in the UAldo:C
      was maintained for the 7 days of the study in both groups. Enalapril decreased
      plasma ACE activity; however, it did not suppress furosemide-induced RAAS
      activation, as determined by the UAldo:C. While enalapril blunts ACE activity,
      the absence of circulating RAAS suppression may be due to angiotensin II
      reactivation, alternative RAAS pathways, and furosemide overriding concurrent ACE
      inhibition, all indicating the existence of aldosterone breakthrough (ABT). Along
      with similar findings with benazepril, it appears that failure to suppress
      aldosterone suppression with furosemide stimulation may be a drug class effect.
      The discrepancy between the current data and the documented benefits of enalapril
      likely reflects the efficacy of this ACE inhibitor in suppressing tissue RAAS,
      variable population responsiveness to ACE-inhibition, and/or providing additional
      survival benefits, possibly through as yet unknown mechanisms.

PMID- 25771847
TI  - [Trends in the prevalence of pressure ulcers in an acute care tertiary hospital
      (2006-2013)].
AB  - OBJECTIVES: To analyse the trends in pressure ulcer prevalence from 2006 to 2013.
      To determine the main risk factors associated with pressure ulcers. METHOD: A
      descriptive study analysing the prevalence in a series of pressure ulcers
      collected in the study on the prevalence of nosocomial infections in Spain from
      2006 to 2013 in the Clinical University Hospital of Zaragoza. RESULTS: The mean
      prevalence among the 5,354 patients included over the period of study was 4.5%
      (95% CI=3.9-5.0%). No significant difference in its trend or distribution of
      pressure ulcers was observed over the several years of the study. Prevalence
      increased up to 5.0% (95% CI=4.4-5.6%) when short-stay patients (less than 24
      hours) and those admitted into low risk units (Paediatrics, Psychiatry and
      Obstetrics) were removed from the study, but there was still no significant
      differences in its yearly trend or distribution (p>0.05). Age, length of stay,
      presence of coma, in-dwelling urethral catheters, malnutrition, infection, and
      admission unit were risk factors associated with pressure ulcer prevalence in the
      logistic regression. CONCLUSIONS: Age, length of stay, coma, in-dwelling urethral
      catheters, malnutrition, infection, and admission unit were independent risk
      markers for patients with pressure ulcers. No particular trend of pressure ulcer
      prevalence could be determined to demonstrate any effects from the different
      strategies of improvement implemented during the period of study, although this
      fact could be due to the limitations of data used in the study.

PMID- 25771848
TI  - [In search of patient experiences].

PMID- 25771849
TI  - The effect of methylphenidate on sustained attention among adolescents with
      attention-deficit hyperactivity disorder.
AB  - Twenty-seven adolescents diagnosed as having attention-deficit hyperactivity
      disorder (ADHD) were tested twice with a computerized MATH-CPT (mathematics
      continuous performance test). In one administration, the participants took
      medication (methylphenidate, MPH) 1.5 hr before being tested. In another
      administration, the MATH-CPT was administered without the medication. Treatment
      with MPH improved the "overall attention level" and in measures of "reaction
      time" and "impulsivity." MPH did not improve the performance in the four measures
      of sustained attention. Knowing that treatment with MPH does not improve
      sustained attention can be helpful in reaching a decision of whether or not a
      child should be treated with MPH.

PMID- 25771850
TI  - Does rural residence impact total ankle arthroplasty utilization and outcomes?
AB  - The objective of this study was to compare total ankle arthroplasty (TAA)
      utilization and outcomes by patient residence. We used the Nationwide Inpatient
      Sample (NIS) from 2003 to 2011 to compare utilization and outcomes (post
      arthroplasty discharge disposition, length of hospitalization, and mortality) by
      rural vs. urban residence. Ten thousand eight hundred thirty-three patients in
      urban and 3,324 patients in rural area underwent TAA. Compared to rural
      residents, urban residents had: lower mean age, 62.4 vs. 61.8 years (p < 0.0001);
      higher percent of women, 49 vs. 56 % (p = 0.0008); and lower proportion of
      Whites, 93 vs. 86 % (p = 0.0005). There were rural-urban disparities in TAA
      utilization in 2003 (0.32 vs. 0.39/100,000; p = 0.021), but not in 2011 (1.19 vs.
      1.17/100,00; p = 0.80). TAA outcomes did not differ by rural vs. urban residence:
      (1) 11.3 % rural vs. 14.2 % urban residents were discharged to an inpatient
      facility (p = 0.098); (2) length of hospital stay above the median stay, was 44.8
      vs. 42.2 % (p = 0.30); and (3) mortality was 0.2 vs. 0.1 %, respectively (p =
      0.81). Multivariable-adjusted logistic regression models did not show any
      significant differences in discharge to home, length of stay, or mortality, by
      residence. Our study demonstrated an absence of any evidence of rural-urban
      differences in TAA outcomes. The rural-urban differences in TAA utilization noted
      in 2003 were no longer significant in 2011.

PMID- 25771851
TI  - Rosuvastatin improves endothelial dysfunction in ankylosing spondylitis.
AB  - Enhanced cardiovascular risk in ankylosing spondylitis (AS) provides a strong
      rationale for early therapeutical intervention. In view of the proven benefit of
      statins in atherosclerotic vascular disease, we aimed to investigate the effect
      of rosuvastatin on endothelial dysfunction (ED) and inflammatory disease activity
      in AS. In a single-blind, placebo-controlled, parallel study, 32 AS patients were
      randomized to receive 24 weeks of treatment with rosuvastatin (10 mg/day, n = 17)
      and placebo (n = 15) as an adjunct to existing stable antirheumatic drugs. Flow
      mediated dilatation (FMD) was assessed by AngioDefenderTM (Everest Genomic Ann
      Arbor, USA). Inflammatory measures (BASDAI, BASFI, CRP and ESR) and pro
      inflammatory cytokines (tumour necrosis factor-alpha [TNF-alpha], interleukin-6
      [IL-6] and interleukin-1 [IL-1]) were measured at baseline and after treatment.
      Lipids and adhesion molecules (intracellular adhesion molecule [ICAM-1] and
      vascular cell adhesion molecule [VCAM-1]) were estimated at baseline and after
      treatment. At baseline, inflammatory measures, pro inflammatory cytokines and
      adhesion molecules were elevated among both groups. After treatment with
      rosuvastatin, FMD improved significantly (p < 0.01). Levels of inflammatory
      measures, TNF-alpha, IL-6 and ICAM-1 decreased significantly (p < 0.01) after
      treatment with rosuvastatin. Rosuvastatin exerted positive effect on lipid
      spectrum. No significant change in the placebo group. Significant negative
      correlation was observed between FMD and IL-6, ICAM-1, CRP after treatment with
      rosuvastatin. First study to show that rosuvastatin improves inflammatory disease
      activity and ED in AS. Rosuvastatin lowers the proinflammatory cytokines,
      especially IL-6 and TNF-alpha, which downregulates adhesion molecules and CRP
      production which in turns improves ED. Improvement in ED in AS occurs through
      both cholesterol-independent and cholesterol-dependent pathways. Rosuvastatin can
      mediate modest but clinically apparent anti-inflammatory effects with
      modification of vascular risk factors in the context of high-grade autoimmune
      inflammation of AS. 

PMID- 25771852
TI  - Effects of home-based exercise intervention on health-related quality of life for
      patients with ankylosing spondylitis: a meta-analysis.
AB  - The objective of this paper was to objectively evaluate the effectiveness of home
      based exercise interventions for improving health-related quality of life in
      patients with ankylosing spondylitis (AS). Databases including PubMed, Web of
      Science, EMBASE, Ovid-Medline, and The Cochrane Library were electronically
      searched published from inception through October 2014 involving home-based
      exercise intervention in AS patients. Studies that measured the Bath Ankylosing
      Spondylitis Functional Index (BASFI), the Bath Ankylosing Spondylitis Disease
      Activity Index (BASDAI), depression and pain as outcomes were included. Studies
      involving patients with multiple diseases or received combinations of other
      interventions were excluded. Two independent investigators screened the
      identified articles, extracted the data, and assessed the methodological quality
      of the included studies. Qualitative descriptions were conducted, and
      quantitative analysis was performed with RevMan software (version 5.2). A total
      of six studies comprising 1098 participants were included in the study. Meta
      analyses showed that home-based exercise interventions significantly reduced the
      BASFI scores (MD = -0.39, 95 % CI -0.57, -0.20, p = 0.001), BASDAI scores (MD = 
      0.50, 95 % CI -0.99, -0.02, p = 0.04), depression scores (MD = -2.31, 95 % CI 
      3.33, -1.30, p = 0.001), and for pain scores because of different evaluation
      methods among these studies; therefore, a subgroup analysis should be conducted
      for comparison. The results show that home-based exercise interventions can
      effectively improve the health-related quality of life in patients with AS. The
      benefit and clinical performance of home-based exercise care requires further
      investigation by a series of multicenter, large-sample size randomized controlled
      trails. 

PMID- 25771853
TI  - Daily practice feasibility and effectiveness of treating long-standing rheumatoid
      arthritis to target with synthetic disease-modifying antirheumatic drugs: a
      prospective cohort study.
AB  - To prospectively study the daily practice feasibility and effectiveness of treat
      to-target (T2T) strategy with synthetic drugs aiming to maintain and achieve
      disease remission or low activity based on DAS28 and CDAI in long-standing
      rheumatoid (RA) patients. Two hundred and forty-one consecutive RA patients from
      Hospital de Clinicas de Porto Alegre were followed for 14 (+/-5.3) months. At
      follow-up, patients were evaluated by a rheumatologist at least once every 3 to 4
      months. Treatment was adjusted following a step-up strategy, based on the disease
      activity scores (DAS28 and CDAI), aiming at remission (<2.6 or <2.8,
      respectively) or at least low disease activity (<3.2 or <10). Patients were
      predominantly women (84.7 %), mean age 54.9 (+/-11.9) years with 11.1 (+/-7.4)
      years of disease duration. At visit 4, T2T intervention significantly reduced
      DAS28 (4.6 +/- 1.6 vs. 4.0 +/- 1.5; p < 0.005), CDAI [17.8 (8.2-28.7) vs. 12.6
      (5.1-22.5); p < 0.001], and HAQ (1.5 +/- 0.9 vs. 1.3 +/- 0.8; p = 0.002). At the
      end of the study, compared to the baseline scores, more patients achieved
      remission by DAS28 (11.6 vs. 18.6 %; p < 0.001) and CDAI (8.1 vs. 13.6 %; p <
      0.001) and also low disease activity by DAS28 (9.8 vs. 13.0 %; p < 0.001) and
      CDAI (23.9 vs. 28.4 %; p < 0.001). Both average doses of sulfasalazine and
      methotrexate at visit 4 were higher (1375 vs. 1621 mg, p = 0.024; and 14.5 vs.
      16.5 mg, p < 0.001, respectively). More patients were on combination therapy at
      the end of the follow-up (48.2 vs. 52.3 %; p < 0.001). The implementation of T2T
      strategy in the treatment of RA was feasible and effective in this outpatient
      population. The optimization of synthetic DMARDs use with dose adjustments and
      combinations of drugs seemed to improve disease outcome regarding disease
      activity and functional status. 

PMID- 25771854
TI  - Reduced folate carrier-1 80G > A gene polymorphism is not associated with
      methotrexate treatment response in South Indian Tamils with rheumatoid arthritis.
AB  - Methotrexate (MTX) is the most commonly used disease-modifying drug to treat
      rheumatoid arthritis (RA). Although there are no reliable molecular markers to
      predict the treatment response and adverse effects to MTX therapy, the
      polymorphisms in genes coding for MTX metabolizing enzymes and transporters may
      play a crucial role. The reduced folate carrier-1 (RFC-1) is a bidirectional
      anion exchanger which transports MTX and folinic acid. It is reported to
      influence MTX treatment response and adverse effects in some ethnic populations
      but not in others. It is also associated with susceptibility to various diseases
      including systemic lupus erythematosus (SLE). The present study was aimed at
      investigating the role of RFC-1 80G > A gene polymorphism in association with
      disease susceptibility, MTX treatment response and the MTX-induced adverse events
      in the South Indian Tamil patients with rheumatoid arthritis. The RFC-1 80G > A
      gene polymorphism was investigated in 327 patients with RA and in 322 healthy
      controls by PCR-RFLP method. It was found that the heterozygous RFC-1 80 GA
      genotype was associated with protection against RA [p = 0.02, odds ratio (OR)
      0.69, 95 % confidence interval (CI) 0.50-0.95]. However, it was not found to be
      associated with MTX treatment response. The RFC-1 G allele frequency was higher
      in patients with adverse effects, but the difference was not statistically
      significant (p = 0.08, OR 1.44, 95 % CI 0.97-2.13). RFC-1 80G > A gene
      polymorphism confers protection for RA. However, it is not associated with MTX
      treatment response and MTX-induced adverse effects in South Indian Tamil patients
      with RA. 

PMID- 25771855
TI  - New palladium(II) and platinum(II) 5,5-diethylbarbiturate complexes with 2
      phenylpyridine, 2,2'-bipyridine and 2,2'-dipyridylamine: synthesis, structures,
      DNA binding, molecular docking, cellular uptake, antioxidant activity and
      cytotoxicity.
AB  - Novel palladium(ii) and platinum(ii) complexes of 5,5-diethylbarbiturate (barb)
      with 2-phenylpyridine (Hppy), 2,2'-bipyridine (bpy) and 2,2'-dipyridylamine
      (dpya) have been prepared and characterized by elemental analysis, IR, UV-Vis,
      NMR and ESI-MS. Single-crystal diffraction measurements show that complex
      consists of binuclear [Pd2(MU-barb-kappaN,O)2(ppy-kappaN,C)2] moieties, while
      complexes are mononuclear, [M(barb-kappaN)2(L-kappaN,N')] (L = bpy or dpya). has
      a composition of [Pt(dpya-kappaN,N')2][Ag(barb-kappaN)2]2.4H2O and was assumed to
      have a structure of [Pt(barb-kappaN)(Hppy-kappaN)(ppy-kappaN,C)].3H2O. The
      complexes were found to exhibit significant DNA binding affinity by a non
      covalent binding mode, in accordance with molecular docking studies. In addition,
      complexes and displayed strong binding with supercoiled pUC19 plasmid DNA.
      Cellular uptake studies were performed to assess the subcellular localization of
      the selected complexes. A moderate radical scavenging activity of and was
      confirmed by DPPH and ABTS tests. Complexes , , and showed selectivity against HT
      29 (colon) cell line. 

PMID- 25771856
TI  - Practice when minimal phototoxic and minimal erythema doses are not determinable.

PMID- 25771857
TI  - Interaction between Bacillus subtilis YsxC and ribosomes (or rRNAs).
AB  - YsxC is an essential P-loop GTPase, that binds to the 50S ribosomal subunit, and
      is required for the proper assembly of the ribosome. The aim of this study was to
      characterize YsxC ribosome interactions. The stoichiometry of YsxC ribosome
      subunit complex was evaluated. We showed that YsxC binding to the 50S ribosomal
      subunit is not affected by GTP, but in the presence of GDP the stoichiometry of
      YsxC-ribosome is decreased. YsxC GTPase activity was stimulated upon 50S
      ribosomal subunit binding. In addition, it is shown for the first time that YsxC
      binds both 16S and 23S ribosomal RNAs. 

PMID- 25771858
TI  - Plasmodium falciparum CTP:phosphocholine cytidylyltransferase possesses two
      functional catalytic domains and is inhibited by a CDP-choline analog selected
      from a virtual screening.
AB  - Phosphatidylcholine is the major lipid component of the malaria parasite
      membranes and is required for parasite multiplication in human erythrocytes.
      Plasmodium falciparum CTP:phosphocholine cytidylyltransferase (PfCCT) is the rate
      limiting enzyme of the phosphatidylcholine biosynthesis pathway and thus
      considered as a potential antimalarial target. In contrast to its mammalian
      orthologs, PfCCT contains a duplicated catalytic domain. Here, we show that both
      domains are catalytically active with similar kinetic parameters. A virtual
      screening strategy allowed the identification of a drug-size molecule
      competitively inhibiting the enzyme. This compound also prevented
      phosphatidylcholine biosynthesis in parasites and exerted an antimalarial effect.
      This study constitutes the first step towards a rationalized design of future new
      antimalarial agents targeting PfCCT. 

PMID- 25771859
TI  - A Drosophila-centric view of protein tyrosine phosphatases.
AB  - Most of our knowledge on protein tyrosine phosphatases (PTPs) is derived from
      human pathologies and mouse knockout models. These models largely correlate well
      with human disease phenotypes, but can be ambiguous due to compensatory
      mechanisms introduced by paralogous genes. Here we present the analysis of the
      PTP complement of the fruit fly and the complementary view that PTP studies in
      Drosophila will accelerate our understanding of PTPs in physiological and
      pathological conditions. With only 44 PTP genes, Drosophila represents a
      streamlined version of the human complement. Our integrated analysis places the
      Drosophila PTPs into evolutionary and functional contexts, thereby providing a
      platform for the exploitation of the fly for PTP research and the transfer of
      knowledge onto other model systems. 

PMID- 25771860
TI  - ROCK2 promotes HCC proliferation by CEBPD inhibition through phospho
      GSK3beta/beta-catenin signaling.
AB  - Rho-associated kinase 2 (Rock2) is known to promote tumorigenesis in
      hepatocellular carcinoma (HCC). CCAAT/enhancer-binding protein delta (CEBPD)
      functions as a tumor suppressor. In this study, we found that the expression of
      Rock2 and CEBPD are inversely correlated. Knockdown of Rock2 increased CEBPD
      expression and inhibited the proliferation of HCC cells in vitro and in vivo.
      Mechanistically, we found that Rock2 regulates CEBPD expression through the p
      GSK3beta/beta-catenin pathway. Taken together, we identified a novel Rock2-p
      GSK3beta/beta-catenin-CEBPD regulatory circuitry, the dysfunction of which may
      contribute to the tumorigenic characteristic of HCC. 

PMID- 25771861
TI  - Packing defects functionalize soluble proteins.
AB  - This work explores the participation of protein packing defects, the so-called
      dehydrons, in biochemical events. We delineate the enabling role of dehydrons as
      activators of nucleophilic groups. This activation results from the induction of
      chemical basicity in interfacial water molecules, promoting deprotonation of
      adjacent nucleophiles. Through multiple steering molecular dynamics with pulling
      along the proton-displacement coordinate, we show that nucleophilic groups are
      functionally enabled by nearby dehydrons that promote proton transference. The
      computations are validated against experimentally determined pKa decreases at
      functional sites and biochemical probes of deregulated catalytic activity arising
      from dehydron-generating mutations. 

PMID- 25771862
TI  - Enzyme logic AND-Reset and OR-Reset gates based on a field-effect electronic
      transducer modified with multi-enzyme membrane.
AB  - Capacitive field-effect sensors modified with a multi-enzyme membrane have been
      applied for an electronic transduction of biochemical signals processed by enzyme
      based AND-Reset and OR-Reset logic gates. The local pH change at the sensor
      surface induced by the enzymatic reaction was used for the activation of the
      Reset function for the first time. 

PMID- 25771863
TI  - Preliminary findings on identification of mycorrhizal fungi from diverse orchids
      in the Central Highlands of Madagascar.
AB  - The Orchid flora of Madagascar is one of the most diverse with nearly 1000 orchid
      taxa, of which about 90% are endemic to this biodiversity hotspot. The Itremo
      Massif in the Central Highlands of Madagascar with a Highland Subtropical climate
      range encompasses montane grassland, igneous and metamorphic rock outcrops, and
      gallery and tapia forests. Our study focused on identifying culturable
      mycorrhizae from epiphytic, lithophytic, and terrestrial orchid taxa to
      understand their diversity and density in a spatial matrix that is within the
      protected areas. We have collected both juvenile and mature roots from 41 orchid
      taxa for isolating their orchid mycorrhizal fungi (OMF), and to culture,
      identify, and store in liquid nitrogen for future studies. Twelve operational
      taxonomic units (OTUs), of three known orchid mycorrhizal genera, were recognized
      by analysis of internal transcribed spacer (ITS) sequences of 85 isolates, and,
      by comparing with GenBank database entries, each OTU was shown to have closely
      related fungi that were also found as orchid associates. Orchid and fungal
      diversity were greater in gallery forests and open grasslands, which is very
      significant for future studies and orchid conservation. As far as we know, this
      is the first ever report of detailed identification of mycorrhizal fungi from
      Madagascar. This study will help start to develop a programme for identifying
      fungal symbionts from this unique biodiversity hotspot, which is undergoing rapid
      ecosystem damage and species loss. The diversity of culturable fungal associates,
      their density, and distribution within the Itremo orchid hotspot areas will be
      discussed.

PMID- 25771864
TI  - Variation of arbuscular mycorrhizal fungal communities along an altitudinal
      gradient in rupestrian grasslands in Brazil.
AB  - Variation in arbuscular mycorrhizal fungi (AMF) communities is described for the
      first time in rupestrian grasslands in Brazil along an altitudinal gradient of
      700 m (800 to 1400 m a.s.l.). Hypotheses tested were that soil properties
      influence the variation in AMF communities and that the frequency of the most
      common species of AMF is inversely influenced by the richness of other AMF. Field
      and laboratory data were collected on AMF community composition, richness,
      density, and frequency in the altitudinal gradient, and the relationships with
      several physical-chemical soil properties and altitude were evaluated. Fifty-one
      species of AMF were recorded, with 14 species being reported as possibly new to
      science and nine species representing new records for Brazil. This single
      elevation gradient alone contains 22% of the known world diversity of AMF. Soil
      properties and AMF community density and richness varied significantly along the
      elevation (p < 0.05). AMF density and richness were higher at the intermediate
      altitude, while AMF species composition differed statistically among the
      altitudes.

PMID- 25771865
TI  - Predictors of survival and functional outcomes in natalizumab-associated
      progressive multifocal leukoencephalopathy.
AB  - Natalizumab, a highly effective therapy for relapsing-remitting multiple
      sclerosis, is associated with a risk of progressive multifocal
      leukoencephalopathy (PML). The objective of this analysis was to examine factors
      predicting survival in a large natalizumab-associated PML global population.
      Patients with natalizumab-associated PML identified through postmarketing
      surveillance were followed up for up to 24 months using a structured
      questionnaire completed by treating physicians. Demographic and clinical
      characteristics, JC viral load, magnetic resonance imaging (MRI) results, and
      Expanded Disability Status Scale (EDSS) and Karnofsky Performance Scale (KPS)
      scores were compared in survivors and nonsurvivors. Kaplan-Meier analysis was
      used to model survival function. Among the 336 patients included in this
      analysis, 76 % survived, with mean follow-up time from PML diagnosis of 16.1
      months for survivors; mean time from diagnosis to death was 4.7 months for
      nonsurvivors. Survivors were significantly younger at diagnosis, had
      significantly lower EDSS scores and higher KPS scores prior to PML diagnosis, and
      had significantly lower cerebrospinal fluid JC viral load at the time of
      diagnosis. Patients with less extensive disease on MRI at diagnosis had a higher
      survival rate than those with widespread disease. Survivors generally had less
      functional disability pre-PML, at PML diagnosis, and in subsequent months. In
      survivors, functional disability appeared to stabilize approximately 6 months
      post-PML diagnosis. In this analysis, younger age at diagnosis, less functional
      disability prior to PML diagnosis, lower JC viral load at diagnosis, and more
      localized brain involvement by MRI at the time of diagnosis appeared to predict
      improved survival in natalizumab-associated PML.

PMID- 25771866
TI  - Formaldehyde-induced histone H3 phosphorylation via JNK and the expression of
      proto-oncogenes.
AB  - Formaldehyde (FA) is a very reactive compound that forms DNA adducts and DNA
      protein crosslinks, which are known to contribute to FA-induced mutations and
      carcinogenesis. Post-translational modifications to histones have recently
      attracted attention due to their link with cancer. In the present study, we
      examined histone modifications following a treatment with FA. FA significantly
      phosphorylated histone H3 at serine 10 (H3S10), and at serine 28 (H3S28), the
      time-course of which was similar to the phosphorylation of H2AX at serine 139
      (gamma-H2AX), a marker of DNA double strand breaks. The temporal deacetylation of
      H3 was observed due to the reaction of FA with the lysine residues of histones.
      The phosphorylation mechanism was then analyzed by focusing on H3S10. The nuclear
      distribution of the phosphorylation of H3S10 and gamma-H2AX did not overlap, and
      the phosphorylation of H3S10 could not be suppressed with an inhibitor of
      ATM/ATR, suggesting that the phosphorylation of H3S10 was independent of the DNA
      damage response. ERK and JNK in the MAPK pathways were phosphorylated by the
      treatment with FA, in which the JNK pathway was the main target for
      phosphorylation. The phosphorylation of H3S10 increased at the promoter regions
      of c-fos and c-jun, indicating a relationship between FA-induced tumor promotion
      activity and phosphorylation of H3S10. These results suggested that FA both
      initiates and promotes cancer, as judged by an analysis of histone modifications.

PMID- 25771867
TI  - Quantifying murine bone marrow and blood radiation dose response following (18)F
      FDG PET with DNA damage biomarkers.
AB  - The purpose of this study was to quantify the poorly understood radiation doses
      to murine bone marrow and blood from whole-body fluorine 18 ((18)F)
      fluorodeoxyglucose (FDG) positron emission tomography (PET), by using specific
      biomarkers and comparing with whole body external low dose exposures. Groups of 3
      5 mice were randomly assigned to 10 groups, each receiving either a different
      activity of (18)F-FDG: 0-37MBq or whole body irradiated with corresponding doses
      of 0-300mGy X-rays. Blood samples were collected at 24h and at 43h for
      reticulocyte micronucleus assays and QPCR analysis of gene expression in
      peripheral blood leukocytes. Blood and bone marrow dose estimates were calculated
      from injected activities of (18)F-FDG and were based on a recommended ICRP model.
      Doses to the bone marrow corresponding to 33.43mGy and above for internal (18)F
      FDG exposure and to 25mGy and above for external X-ray exposure, showed
      significant increases in radiation-induced MN-RET formation relative to controls
      (P<0.05). Regression analysis showed that both types of exposure produced a
      linear response with linear regression analysis giving R(2) of 0.992 and 0.999
      for respectively internal and external exposure. No significant difference
      between the two data sets was found with a P-value of 0.493. In vivo gene
      expression dose-responses at 24h for Bbc3 and Cdkn1 were similar for (18)F-FDG
      and X-ray exposures, with significant modifications occurring for doses over
      300mGy for Bbc3 and at the lower dose of 150mGy for Cdkn1a. Both leucocyte gene
      expression and quantification of MN-RET are highly sensitive biomarkers for
      reliable estimation of the low doses delivered in vivo to, respectively, blood
      and bone marrow, following (18)F-FDG PET. 

PMID- 25771868
TI  - Human CYP2E1-dependent and human sulfotransferase 1A1-modulated induction of
      micronuclei by benzene and its hydroxylated metabolites in Chinese hamster V79
      derived cells.
AB  - Benzene is a ubiquitous environmental pollutant and a confirmed human carcinogen,
      which requires metabolic activation, primarily by CYP2E1, for most of its
      biological actions. Chromosome damages in benzene-exposed workers and rodents
      have been observed, and in their urine sulfo- and glucuronide-conjugates of
      phenol and hydroquinone were present. Yet, direct evidence for human CYP2E1
      activated mutagenicity of benzene and the exact significance of phase II
      metabolism for inactivating benzene metabolites are still missing. In the present
      study, benzene and its oxidized metabolites (phenol, hydroquinone, catechol,
      1,2,4-trihydroxybenzene and 1,4-benzoquinone) were investigated for induction of
      micronuclei in a V79-derived cell line genetically engineered for expression of
      both human CYP2E1 and human sulfotransferase (SULT) 1A1 (indicated by active
      micronuclei induction by 1-hydroxymethylpyrene). The results demonstrated
      concentration-dependent induction of micronuclei by benzene and phenol, though
      with lower potency or efficacy than the other metabolites. Inhibition of CYP2E1
      by 1-aminobenzotriazole did not change the effect of benzoquinone, but completely
      abolished that of benzene and phenol, and attenuated that of the other compounds.
      Moreover, inhibition of SULT1A1 by pentachlorophenol potentiated the effects of
      benzene, hydroquinone, catechol and trihydroxybenzene. Ascorbic acid, a reducing
      and free radical-scavenging agent, significantly lowered the effects of
      hydroquinone, catechol, trihydroxybenzene as well as N-nitrosodimethylamine (a
      known CYP2E1-dependent promutagen), with that of benzoquinone unaffected. These
      results suggest that in addition to activating benzene and phenol, human CYP2E1
      may further convert hydroquinone, catechol and trihydroxybenzene to more
      genotoxic metabolites, and sulfo-conjugation of the multi-hydroxylated
      metabolites of benzene by human SULT1A1 may represent an important detoxifying
      pathway. 

PMID- 25771869
TI  - New tool for biological dosimetry: reevaluation and automation of the gold
      standard method following telomere and centromere staining.
AB  - PURPOSE: The dicentric chromosome (dicentric) assay is the international gold
      standard method for biological dosimetry and classification of genotoxic agents.
      The introduction of telomere and centromere (TC) staining offers the potential to
      render dicentric scoring more efficient and robust. In this study, we improved
      the detection of dicentrics and all unstable chromosomal aberrations (CA) leading
      to a significant reevaluation of the dose-effect curve and developed an automated
      approach following TC staining. MATERIAL AND METHODS: Blood samples from 16
      healthy donors were exposed to (137)Cs at 8 doses from 0.1 to 6Gy. CA were
      manually and automatically scored following uniform (Giemsa) or TC staining. The
      detection of centromeric regions and telomeric sequences using PNA probes allowed
      the detection of all unstable CA: dicentrics, centric and acentric rings, and all
      acentric fragments (with 2, 4 or no telomeres) leading to the precise
      quantification of estimated double strand breaks (DSB). RESULTS: Manual scoring
      following TC staining revealed a significantly higher frequency of dicentrics
      (p<10(-3)) (up to 30%) and estimated DSB (p<10(-4)) compared to uniform staining
      due to improved detection of dicentrics with centromeres juxtaposed with other
      centromeres or telomeres. This improvement permitted the development of the
      software, TCScore, that detected 95% of manually scored dicentrics compared to
      50% for the best currently available software (DCScoreTM). CONCLUSION: The use of
      TC staining has permitted a reevaluation of the dose-response curve and the
      highly efficient automation of the scoring process, marking a new step in the
      management and follow-up of populations exposed to genotoxic agents including
      ionizing radiation.

PMID- 25771870
TI  - Emerging importance of mismatch repair components including UvrD helicase and
      their cross-talk with the development of drug resistance in malaria parasite.
AB  - Human malaria is an important parasitic infection responsible for a significant
      number of deaths worldwide, particularly in tropical and subtropical regions. The
      recent scenario has worsened mainly because of the emergence of drug-resistant
      malaria parasites having the potential to spread across the world. Drug-resistant
      parasites possess a defective mismatch repair (MMR); therefore, it is essential
      to explore its mechanism in detail to determine the underlying cause. Recently,
      artemisinin-resistant parasites have been reported to exhibit nonsynonymous
      single nucleotide polymorphisms in genes involved in MMR pathways such as MutL
      homolog (MLH) and UvrD. Plasmodium falciparum MLH is an endonuclease required to
      restore the defective MMR in drug-resistant W2 strain of P. falciparum. Although
      the role of helicases in eukaryotic MMR has been questioned, the identification
      and characterization of the UvrD helicase and their cross-talk with MLH in P.
      falciparum suggests the possible involvement of UvrD in MMR. A comparative genome
      wide analysis revealed the presence of the UvrD helicase in Plasmodium species,
      while it is absent in human host. Therefore, PfUvrD may emerge as a suitable drug
      target to control malaria. This review study is focused on recent developments in
      MMR biochemistry, emerging importance of the UvrD helicase, possibility of its
      involvement in MMR and the emerging cross-talk between MMR components and drug
      resistance in malaria parasite. 

PMID- 25771871
TI  - The functional polymorphism of NBS1 p.Glu185Gln is associated with an increased
      risk of lung cancer in Chinese populations: case-control and a meta-analysis.
AB  - NBS1 plays pivotal roles in maintaining genomic stability and cancer development.
      The exon variant rs1805794G>C (p.Glu185Gln) of NBS1 has been frequently studied
      in several association studies. However, the results were conflicting. Also, the
      function of this variant has never been well studied. In the current study, we
      performed a two centers case-control study and function assays to investigate the
      effect of the variant rs1805794G>C on lung cancer risk in Chinese, and a meta
      analysis to summarize the data on the association between rs1805794G>C and cancer
      risk. We found that compared with the rs1805794GG genotype, the C genotypes
      (CG/CC) conferred a significantly increased risk of lung cancer in Chinese
      (OR=1.40, 95% CI=1.21-1.62) and interacted with medical ionizing radiation
      exposure on increasing cancer risk (Pinteraction=0.015). The lymphocyte cells
      from the C genotype individuals developed more chromatid breaks than those from
      the GG genotype carriers after the X-ray radiation (P=0.036). Moreover, the
      rs1805794C allele encoding p.185Gln attenuated NBS1's ability to repair DNA
      damage as the cell lines transfected with NBS1 cDNA expression vector carrying
      rs1805794C allele had significantly higher DNA breaks than those transfected with
      NBS1 cDNA expression vector carrying rs1805794G allele (P<0.05). The meta
      analysis further confirmed the association between the variant rs1805794G>C and
      lung cancer risk, that compared with the GG genotype, the carriers of C genotypes
      had a 1.30-fold risk of cancer (95% CI=1.14-1.49, P=8.49*10(-5)). These findings
      suggest that the rs1805794G>C of NBS1 may be a functional genetic biomarker for
      lung cancer. 

PMID- 25771872
TI  - Cytogenetic characterization of low-dose hyper-radiosensitivity in Cobalt-60
      irradiated human lymphoblastoid cells.
AB  - The dose-effect relationships of cells exposed to ionizing radiation are
      frequently described by linear quadratic (LQ) models over an extended dose range.
      However, many mammalian cell lines, when acutely irradiated in G2 at doses
      <=0.3Gy, show hyper-radiosensitivity (HRS) as measured by reduced clonogenic cell
      survival, thereby indicating greater cell lethality than is predicted by
      extrapolation from high-dose responses. We therefore hypothesized that the
      cytogenetic response in G2 cells to low doses would also be steeper than
      predicted by LQ extrapolation from high doses. We tested our hypothesis by
      exposing four normal human lymphoblastoid cell lines to 0-400cGy of Cobalt-60
      gamma radiation. The cytokinesis block micronucleus assay was used to determine
      the frequencies of micronuclei and nucleoplasmic bridges. To characterize the
      dependence of the cytogenetic damage on dose, univariate and multivariate
      regression analyses were used to compare the responses in the low- (HRS) and high
      dose response regions. Our data indicate that the slope of the response for all
      four cell lines at <=20cGy during G2 is greater than predicted by an LQ
      extrapolation from the high-dose responses for both micronuclei and bridges.
      These results suggest that the biological consequences of low-dose exposures
      could be underestimated and may not provide accurate risk assessments following
      such exposures. 

PMID- 25771873
TI  - Mutagenesis in the lacI gene target of E. coli: improved analysis for lacI(d) and
      lacO mutants.
AB  - The lacI gene of Escherichia coli has been a highly useful target for studies of
      mutagenesis, particularly for analysis of the specificity (spectrum) of mutations
      generated under a variety of conditions and in various genetic backgrounds. The
      gene encodes the repressor of the lac operon, and lacI-defective mutants
      displaying constitutive expression of the operon are readily selected. DNA
      sequencing of the lacI mutants has often been confined to the N-terminal region
      of the protein, as it presents a conveniently short target with a high density of
      detectably mutable sites. Mutants in this region are easily selected due to their
      dominance in a genetic complementation test (lacI(d) mutants). A potential
      complication in these studies is that constitutive expression of lac may also
      arise due to mutations in the lac operator (lacO mutants). Under some conditions,
      for example when analyzing spontaneous mutations, lacO mutants can comprise a
      very high fraction of the constitutive mutants due to a strong base-substitution
      hotspot in the lac operator. Such mutational hot spots diminish the return of the
      sequencing effort and do not yield significant new information. For this reason,
      a procedure to eliminate the lacO mutants prior to DNA sequencing is desirable.
      Here, we report a simple method that allows screening out of lacO mutants. This
      method is based on the lack of resistance of lacO mutants to kanamycin under
      conditions when the kan gene is expressed from a plasmid under control of the lac
      promoter-operator (lacPO). We show data validating the new approach with sets of
      known lacI(d) and lacO mutants, and further apply it to the generation of a new
      collection of spontaneous mutations, where lacO mutants have historically been a
      significant contributor. 

PMID- 25771874
TI  - Risk-associated coding synonymous SNPs in type 2 diabetes and neurodegenerative
      diseases: genetic silence and the underrated association with splicing regulation
      and epigenetics.
AB  - Single nucleotide polymorphisms (SNPs) are tentatively critical with regard to
      disease predisposition, but coding synonymous SNPs (sSNPs) are generally
      considered "neutral". Nevertheless, sSNPs in serine/arginine-rich (SR) and splice
      site (SS) exonic splicing enhancers (ESEs) or in exonic CpG methylation targets,
      could be decisive for splicing, particularly in aging-related conditions, where
      mis-splicing is frequently observed. We presently identified 33 genes T2D-related
      and 28 related to neurodegenerative diseases, by investigating the impact of the
      corresponding coding sSNPs on splicing and using gene ontology data and
      computational tools. Potentially critical (prominent) sSNPs comply with the
      following criteria: changing the splicing potential of prominent SR-ESEs or of
      significant SS-ESEs by >1.5 units (Deltascore), or formation/deletion of ESEs
      with maximum splicing score. We also noted the formation/disruption of CpGs
      (tentative methylation sites of epigenetic sSNPs). All disease association
      studies involving sSNPs are also reported. Only 21/670 coding SNPs, mostly
      epigenetic, reported in 33 T2D-related genes, were found to be prominent coding
      synonymous. No prominent sSNPs have been recorded in three key T2D-related genes
      (GCGR, PPARGC1A, IGF1). Similarly, 20/366 coding synonymous were identified in ND
      related genes, mostly epigenetic. Meta-analysis showed that 17 of the above
      prominent sSNPs were previously investigated in association with various
      pathological conditions. Three out of four sSNPs (all epigenetic) were associated
      with T2D and one with NDs (branch site sSNP). Five were associated with other or
      related pathological conditions. None of the four sSNPs introducing new ESEs was
      found to be disease-associated. sSNPs introducing smaller Deltascore changes
      (<1.5) in key proteins (INSR, IRS1, DISC1) were also correlated to pathological
      conditions. This data reveals that genetic variation in splicing-regulatory and
      particularly CpG sites might be related to disease predisposition and that in
      silico analysis is useful for identifying sSNPs, which might be falsely
      identified as silent or synonymous. 

PMID- 25771875
TI  - Analysis of gene expression changes in A549 cells induced by organic compounds
      from respirable air particles.
AB  - A number of toxic effects of respirable ambient air particles (genotoxic effects,
      inflammation, oxidative damage) have been attributed to organic compounds bound
      onto the particle surface. In this study, we analyzed global gene expression
      changes caused by the extractable organic matters (EOMs) from respirable airborne
      particles <2.5MUm (PM2.5), collected at 3 localities from heavily polluted areas
      of the Czech Republic and a control locality with low pollution levels, in human
      lung epithelial A549 cells. Although the sampled localities differed in both
      extent and sources of air pollution, EOMs did not induce substantially different
      gene expression profiles. The number of transcripts deregulated in A549 cells
      treated with the lowest EOM concentration (10MUg/ml) ranged from 65 to 85 in 4
      sampling localities compared to the number of transcripts deregulated after
      30MUg/ml and 60MUg/ml of EOMs, which ranged from 90 to 109, and from 149 to 452,
      respectively. We found numerous commonly deregulated genes and pathways related
      to activation of the aryl hydrocarbon receptor (AhR) and metabolism of
      xenobiotics and endogenous compounds. We further identified deregulation of
      expression of the genes involved in pro-inflammatory processes, oxidative stress
      response and in cancer and developmental pathways, such as TGF-beta and Wnt
      signaling pathways. No cell cycle arrest, DNA repair or pro-apoptotic responses
      were identified at the transcriptional level after the treatment of A549 cells
      with EOMs. In conclusion, numerous processes and pathways deregulated in response
      to EOMs suggest a significant role of activated AhR. Interestingly, we did not
      observe substantial gene expression changes related to DNA damage response,
      possibly due to the antagonistic effect of non-genotoxic EOM components.
      Moreover, a comparison of EOM effects with other available data on modulation of
      global gene expression suggests possible overlap among the effects of PM2.5, EOMs
      and various types of AhR agonists. 

PMID- 25771876
TI  - The germline CDH1 c.48 G>C substitution contributes to cancer predisposition
      through generation of a pro-invasive mutation.
AB  - Mutation screening of CDH1 is a standard of care for patients who meet criteria
      for Hereditary Diffuse Gastric Cancer (HDGC). In this setting, the classification
      of the sequence variants found in CDH1 is a critical step for risk management of
      patients with HDGC. In this report, we describe a germline CDH1 c.48 G>C variant
      found in a 21 year old woman and her living great uncle, who were both diagnosed
      with gastric cancer and belong to a family with high incidence of this type of
      cancer. This variant occurs at the last nucleotide of exon 1 and presumably
      results in a Gln-to-His change at codon 16 (Q16H). We used cloning strategies to
      evaluate the effects on mRNA stability and found that 5/27 and 0/17 clones have
      the "C" mutant allele in patient and her great uncle, respectively. In vitro
      functional studies revealed that the germline missense mutant (Q16H) had a pro
      invasive cell behavior. Both results (functional and clinical) support the
      conclusion that the CDH1 c.48 G>C (Q16H) variant contributes to HDGC through the
      generation of a pathogenic missense mutation with loss of anti-invasive function.

PMID- 25771877
TI  - Phosphorylation of PTEN at STT motif is associated with DNA damage response.
AB  - Phosphatase and tensin homolog deleted on chromosome Ten (PTEN), a tumor
      suppressor protein participates in multiple cellular activities including DNA
      repair. In this work we found a relationship between phosphorylation of carboxy
      (C)-terminal STT motif of PTEN and DNA damage response. Ectopic expression of C
      terminal phospho-mutants of PTEN, in PTEN deficient human glioblastoma cells,
      U87MG, resulted in reduced viability and DNA repair after etoposide induced DNA
      damage compared to cells expressing wild type PTEN. Also, after etoposide
      treatment phosphorylation of PTEN increased at C-terminal serine 380 and
      threonine 382/383 residues in PTEN positive HEK293T cells and wild type PTEN
      transfected U87MG cells. One-step further, DNA damage induced phosphorylation of
      PTEN was confirmed by immunoprecipitation of total PTEN from cellular extract
      followed by immunobloting with phospho-specific PTEN antibodies. Additionally,
      phospho-PTEN translocated to nucleus after etoposide treatment as revealed by
      indirect immunolabeling. Further, phosphorylation dependent nuclear foci
      formation of PTEN was observed after ionizing radiation or etoposide treatment
      which colocalized with gammaH2AX. Additionally, etoposide induced gammaH2AX,
      Mre11 and Ku70 foci persisted for a longer period of times in U87MG cells after
      ectopic expression of PTEN C-terminal phospho-mutant constructs compared to wild
      type PTEN expressing cells. Thus, our findings strongly suggest that DNA damage
      induced phosphorylation of C-terminal STT motif of PTEN is necessary for DNA
      repair. 

PMID- 25771878
TI  - Optimal standard regimen and predicting response to docetaxel therapy.
AB  - The purpose of this research is optimizing and predicting the potent activity of
      docetaxel through an efficient regimen to settle down a new protocol for the
      treatment of cancer. Effectiveness of docetaxel was examined in vivo in several
      mouse models engrafted either subcutaneously or intravenously with several types
      of cell lines. The effects of 147-5040mg/L of docetaxel in treatments of
      different regimens in those xenograft growths were monitored and quantified to
      identify energy of those doses as described before in earlier studies. Mock
      processes were performed on untreated groups of mice for controls. Docetaxel had
      significant influence on all sizes of treated tumors compared to the control
      animals. The longer the induced tumor doubling time intraday to more than half
      the time period from the start of therapy to the time of delivery of the dose,
      the higher the energy of docetaxel doses and hence the effectiveness of the
      treatment and vice versa. The energy yield by drug doses in optimal standard
      regimens was perfectly power correlated (r=1) with the drug dose. An efficient
      dose-energy model with a perfect fit (R(2)=1) estimating the energy yield by
      docetaxel doses in optimal standard regimens has been established to administer
      the personalized dose. Administration of docetaxel doses should be patient
      specific and sufficient for the suggested regimen. Time periods from the start of
      therapy to the time of dose delivery of the efficient regimen are shorter than
      twice the tumor doubling time intraday on time of dose delivery. Patients with
      tumors of lower mitotic index may particularly benefit more from optimal standard
      regimens, whereas metronomic regimens would be more efficient in patients with
      tumors of higher mitotic index that need lower doses of docetaxel. 

PMID- 25771879
TI  - High levels of gamma-H2AX foci and cell membrane oxidation in adolescents with
      type 1 diabetes.
AB  - Oxidative stress caused by an excess of free radicals is implicated in the
      pathogenesis and development of type 1 diabetes mellitus (T1DM) and, in turn, it
      can lead to genome damage, especially in the form of DNA double-strand break
      (DSB). The DNA DSB is a potentially carcinogenic lesion for human cells. Thus, we
      aimed to evaluate whether the level of oxidative stress was increased in
      peripheral blood lymphocytes of a group of affected adolescents. In 35 T1DM
      adolescents and 19 healthy controls we assessed: (1) spontaneous and H2O2-induced
      oxidation of cell membrane using a fluorescence lipid probe; (2) spontaneous and
      LPS-induced expression of iNOS protein and indirect NO determination via
      cytofluorimetric analysis of O2(-); (3) immunofluorescent detection of the basal
      level of histone H2AX phosphorylation (gamma-H2AX foci), a well-validated marker
      of DNA DSB. In T1DM, the frequencies of oxidized cells, both spontaneous and H2O2
      induced (47.13+/-0.02) were significantly higher than in controls (35.90+/-0.03).
      Patients showed, in general, both a reduced iNOS expression and production of NO.
      Furthermore, the level of spontaneous nuclear damage, quantified as gamma-H2AX
      foci, was markedly increased in T1DM adolescents (6.15+/-1.08% of gamma-H2AX(+)
      cells; 8.72+/-2.14 gamma-H2AXF/n; 9.26+/-2.37 gamma-H2AXF/np), especially in
      females. In the present study, we confirmed the role that oxidative stress plays
      in the disease damaging lipids of cell membrane and, most importantly, causing
      genomic damage in circulating white blood cells of affected adolescents. This
      also indicates that oxidative stress can affect several tissues in the body.
      However, although the observed DNA damage is a clear indication that the proper
      DNA repair mechanisms are activated, the risk for young T1DM subjects of
      developing not only cardiovascular complications but also some type of cancer
      cannot be ruled out. In this view, females, probably due to hormonal imbalance
      typical of adolescence, might represent a more susceptible population. 

PMID- 25771880
TI  - Effect of drinking water disinfection by-products in human peripheral blood
      lymphocytes and sperm.
AB  - BACKGROUND: Drinking water disinfection by-products (DBPs) are generated by the
      chemical disinfection of water and may pose hazards to public health. Two major
      classes of DBPs are found in finished drinking water: haloacetic acids (HAAs) and
      trihalomethanes (THMs). HAAs are formed following disinfection with chlorine,
      which reacts with iodide and bromide in the water. Previously the HAAs were shown
      to be cytotoxic, genotoxic, mutagenic, teratogenic and carcinogenic. OBJECTIVES:
      To determine the effect of HAAs in human somatic and germ cells and whether
      oxidative stress is involved in genotoxic action. In the present study both
      somatic and germ cells have been examined as peripheral blood lymphocytes and
      sperm. METHODS: The effects of three HAA compounds: iodoacetic acid (IAA),
      bromoacetic acid (BAA) and chloroacetic acid (CAA) were investigated. After
      determining appropriate concentration responses, oxygen radical involvement with
      the antioxidants, butylated hydroxanisole (BHA) and the enzyme catalase, were
      investigated in the single cell gel electrophoresis (Comet) assay under alkaline
      conditions, >pH 13 and the micronucleus assay. RESULTS: In the Comet assay, BHA
      and catalase were able to reduce DNA damage in each cell type compared to HAA
      alone. In the micronucleus assay, micronuclei (MNi) were found in peripheral
      lymphocytes exposed to all three HAAs and catalase and BHA were in general, able
      to reduce MNi induction, suggesting oxygen radicals play a role in both assays.
      CONCLUSION: These observations are of concern to public health since both human
      somatic and germ cells show similar genotoxic responses.

PMID- 25771881
TI  - Saloplastics: processing compact polyelectrolyte complexes.
AB  - Polyelectrolyte complexes (PECs) are prepared by mixing solutions of oppositely
      charged polyelectrolytes. These diffuse, amorphous precipitates may be compacted
      into dense materials, CoPECs, by ultracentrifugation (ucPECs) or extrusion
      (exPECs). The presence of salt water is essential in plasticizing PECs to allow
      them to be reformed and fused. When hydrated, CoPECs are versatile, rugged,
      biocompatible, elastic materials with applications including bioinspired
      materials, supports for enzymes and (nano)composites. In this review, various
      methods for making CoPECs are described, as well as fundamental responses of
      CoPEC mechanical properties to salt concentration. Possible applications as
      synthetic cartilage, enzymatically active biocomposites, self-healing materials,
      and magnetic nanocomposites are presented. 

PMID- 25771882
TI  - Virus, strain, and epitope specificities of neutralizing bovine monoclonal
      antibodies to bovine herpesvirus 1 glycoproteins gB, gC, and gD, with sequence
      and molecular model analysis.
AB  - Three bovine monoclonal antibodies (BomAb) raised to bovine herpesvirus (BoHV)
      1.1 and specific for the viral glycoproteins gB, gC, and gD were tested for
      reactivity to two isolates of BoHV-1.1, one of BoHV-1.2, and two of BoHV-5 in
      virus neutralization and indirect fluorescent antibody assays. They were also
      tested with other herpesviruses infecting cattle and other mammalian
      alphaherpesviruses, and found negative or of negligible reactivity. Their BoHV
      1.1 epitope specificity was examined using competitive ELISA with peroxidase
      labeled murine monoclonal antibodies (MumAb) that had been previously
      characterized. To explain the incongruities observed, the amino acid sequences of
      the epitopes and adjacent regions of BoHV-1.1, 1.2, and 5 were compared, and
      molecular modeling was performed using human herpesvirus 1 glycoprotein crystals
      as templates. The anti-gB BomAb reacted strongly with BoHV-1.1 and BoHV-1.2, and
      poorly or not at all with BoHV-5. It competed with a MumAb specific for a BoHV
      1.1 gB epitope previously shown to only partially cross-react between BoHV-1 and
      BoHV-5. BoHV-5 gB has nearly identical sequence with BoHV-1.1 in the epitope
      region, but modeling suggested the lack of cross-reactivity of the MumAb was due
      to masking of the epitope in BoHV-5 by an adjacent region, which has significant
      sequence differences between BoHV-1.1 and BoHV-5. The BomAb reactivity could also
      be explained by masking, or by reactivity with the adjacent region. The anti-gC
      BomAb reacted strongly with one isolate of BoHV-1.1 and BoHV-1.2, less well with
      a heterologous isolate of BoHV-1.1, and poorly or not at all with BoHV-5. It did
      not compete with any of the anti-gC MumAb tested, but a target domain was
      suggested by BoHV-1.1, 1.2, and 5 sequence divergence. The anti-gD BomAb reacted
      strongly with all BoHV-1.1, 1.2, and 5 isolates tested. However, it competed with
      two MumAb previously shown to not cross-react between BoHV-1.1 and BoHV-5.
      Sequence analysis and modeling suggested the cross-reactivity of the anti-gD
      BomAb was due to it reacting with an epitope-adjacent region or regions conserved
      between BoHV-1.1 and BoHV-5, but not with other alphaherpesviruses. The results
      suggest the usefulness of combining in vitro biological data with sequence or
      structure modeling data to investigate important epitopes involved in immunity to
      infectious agents. 

PMID- 25771883
TI  - An Educational Intervention to Increase Nurse Adherence in Eliciting Patient
      Daily Goals.
AB  - BACKGROUND: The literature suggests that nurse and patient collaborative goal
      setting demonstrates better patient outcomes. The SMART goal evaluation method
      (Specific, Measureable, Attainable, Relevant, and Timely) is a strategy to
      develop effective and measureable goals. PURPOSE: The purpose of this educational
      project was to improve nurse collaborative goal-setting skills. METHODS: A pre-
      and postevaluation of an educational intervention was accomplished by patient
      interviews and observation for adherence to obtaining patient daily goals.
      RESULTS: Results of nurse adherence in writing SMART collaborative goal setting
      increased from 11% preeducation to 63% posteducation. Patients' perceptions of
      feeling well informed by their nurses and physicians increased from 57%
      preeducation to 91% posteducation. CONCLUSION: Nurses continued to need reminding
      to collaborate with their patients, but their goal writing skills greatly
      improved. CLINICAL RELEVANCE: The results of this educational project
      demonstrated nurses' improved ability to cowrite collaborative patient goals
      which resulted in better informed patients.

PMID- 25771884
TI  - Increased chemokine (C-C motif) ligand 21 expression and its correlation with
      osteopontin in Graves' disease.
AB  - Graves' disease (GD) is a chronic autoimmune process characterized by the
      production of auto-antibodies that presumably consequent to the lymphocytic
      infiltrates in the thyroid. Chemokine (C-C motif) ligand 21 (CCL21) is important
      for the circulation of CC-chemokine receptor 7 (CCR7)-expressing cells.
      Meanwhile, osteopontin (OPN) enhances the production of proinflammatory cytokines
      and chemokines through NF-kappaB and MAPK signaling pathways in GD. Although
      CCL21 has been reported to play a vital role in several autoimmune diseases,
      little is known about the relationship between CCL21 and GD development. This
      study aimed to detect the CCL21 level in GD and to examine the role of OPN in
      regulating CCL21 production. 40 initial GD patients, 15 euthyroid GD patients, 12
      TRAb-negative GD patients, and 25 healthy control donors were recruited. CCL21
      levels in plasma and culture supernatants were quantified by enzyme-linked
      immunosorbent assay (ELISA). CD4+ T cells were isolated from peripheral blood
      mononuclear cells using antibody-coated magnetic beads. Quantitative polymerase
      chain reaction was used to determine CCL21 expression levels in CD4+ T cells. We
      demonstrated for the first time that plasma CCL21 levels were overexpressed in GD
      patients and recovered in TRAb-negative GD patients. Moreover, CCL21 levels
      correlated with TRAb levels and plasma OPN concentrations. Furthermore, we
      demonstrated that recombinant OPN increased the expression of CCL21 in a dose-
      and time-dependent manner. These data indicated a clinical correlation between
      plasma CCL21 levels and GD. CCL21 could serve as a novel biomarker for GD as well
      as a potential target for TRAb-positive GD treatment.

PMID- 25771885
TI  - Determinants of testosterone levels in human male obesity.
AB  - Testosterone (T) levels are decreased in obese men, but the underlying causes are
      incompletely understood. Our objective was to explore the relation between low
      (free) T levels and male obesity, by evaluating metabolic parameters,
      subcutaneous adipose tissue (SAT) aromatase expression, and parameters of the
      hypothalamic-pituitary-gonadal axis. We recruited 57 morbidly obese men [33 had
      type 2 diabetes (DM2)] and 25 normal-weight men undergoing abdominal surgery.
      Fourteen obese men also attended a follow-up, 2 years after gastric bypass
      surgery (GBS). Circulating T levels were quantified by LC-MS/MS, whereas free T
      levels were measured using serum equilibrium dialysis and sex hormone-binding
      globulin, luteinizing hormone, and follicle-stimulating hormone by immunoassay.
      SAT biopsies were used to determine adipocyte cell size and aromatase expression
      by real-time PCR. Total and free T levels were decreased in obese males versus
      controls, with a further decrease in obese men with DM2 versus obese men without
      DM2. There were no differences in aromatase expression among the study groups,
      and sex steroids did not correlate with aromatase expression. Pearson analysis
      revealed an inverse association between (free) T and SAT cell size,
      triglycerides, and HOMA-IR. Multivariate analysis confirmed the inverse
      association between (free) T and SAT cell size (beta = -0.321, P = 0.037 and beta
      = -0.441, P = 0.011, respectively), independent of age, triglycerides, HOMA-IR,
      obesity, or diabetes. T levels were normalized 2 years after GBS. These data
      suggest that SAT cell size rather than SAT aromatase expression or parameters of
      the hypothalamic-pituitary-gonadal axis is related to low T in male obesity,
      which points to adipose cell size-related metabolic changes as a major trigger in
      decreased T levels.

PMID- 25771886
TI  - Autocrine effect of Zn2+ on the glucose-stimulated insulin secretion.
AB  - It is well known that zinc (Zn(2+)) is required for the process of insulin
      biosynthesis and the maturation of insulin secretory granules in pancreatic beta
      (beta)-cells, and that changes in Zn(2+) levels in the pancreas have been found
      to be associated with diabetes. Glucose-stimulation causes a rapid co-secretion
      of Zn(2+) and insulin with similar kinetics. However, we do not know whether
      Zn(2+) regulates insulin availability and secretion. Here we investigated the
      effect of Zn(2+) on glucose-stimulated insulin secretion (GSIS) in isolated mouse
      pancreatic islets. Whereas Zn(2+) alone (control) had no effect on the basal
      secretion of insulin, it significantly inhibited GSIS. The application of CaEDTA,
      by removing the secreted Zn(2+) from the extracellular milieu of the islets,
      resulted in significantly increased GSIS, suggesting an overall inhibitory role
      of secreted Zn(2+) on GSIS. The inhibitory action of Zn(2+) was mostly mediated
      through the activities of KATP/Ca(2+) channels. Furthermore, during brief paired
      pulse glucose-stimulated Zn(2+) secretion (GSZS), Zn(2+) secretion following the
      second pulse was significantly attenuated, probably by the secreted endogenous
      Zn(2+) after the first pulse. Such an inhibition on Zn(2+) secretion following
      the second pulse was completely reversed by Zn(2+) chelation, suggesting a
      negative feedback mechanism, in which the initial glucose-stimulated Zn(2+)
      release inhibits subsequent Zn(2+) secretion, subsequently inhibiting insulin co
      secretion as well. Taken together, these data suggest a negative feedback
      mechanism on GSZS and GSIS by Zn(2+) secreted from beta-cells, and the co
      secreted Zn(2+) may act as an autocrine inhibitory modulator.

PMID- 25771888
TI  - REM sleep-associated motor behaviors in Parkinson's disease patients with
      heterozygous Parkin mutations.

PMID- 25771887
TI  - The possible role of CD4+CD25(high)Foxp3+/CD4+IL-17A+ cell imbalance in the
      autoimmunity of patients with Hashimoto thyroiditis.
AB  - Hashimoto thyroiditis (HT) is a prototypic organ-specific autoimmune thyroid
      disease, for which the exact etiology remains unclear. The aim of this study was
      to investigate dynamic changes in regulatory T cell (Treg) and T helper 17 cell
      (Th17) populations in patients with HT at different stages of thyroid
      dysfunction, as well as to analyze the possible correlation between the Treg/Th17
      cell axis and autoimmune status in HT. We assessed thyroid function and
      autoantibody serology both in HT patients and in healthy controls (HCs) and
      divided HT patients into three subgroups according to thyroid function. We then
      determined the percentages of Treg and Th17 cells in peripheral blood mononuclear
      cells and analyzed mRNA expression of the Treg and Th17 cell-defining
      transcription factors Foxp3 and RORgammat. In addition, serum levels of TGF-beta
      and IL-17A were assessed. We found that the percentage of Treg cells, Foxp3 mRNA
      levels, and the ratio of Treg/Th17 cells were all significantly lower in HT
      patients, while Th17 cell percentages and RORgammat mRNA levels were
      significantly higher. Interestingly, we also observed significant differences in
      these measurements between HT patient subgroups. Serum IL-17A levels were
      markedly increased in HT patients, while serum concentrations of TGF-beta were
      lower, compared to HCs. The ratio of Treg/Th17 cells was negatively correlated
      with the levels of serum thyroperoxidase antibody, thyroglobulin antibody, and
      thyrotropin (TSH) in HT patients. Taken together, our data suggest that the
      balance between Treg and Th17 cells shifts in favor of Th17 cells during clinical
      progression of HT, which is negatively correlated with levels of thyroid-specific
      autoantibodies and TSH, implying that Treg/Th17 cell imbalance may contribute to
      thyroid damage in HT.

PMID- 25771890
TI  - Three hen strains fed photoisomerized trans,trans CLA-rich soy oil exhibit
      different yolk accumulation rates and source-specific isomer deposition.
AB  - Most CLA chicken feeding trials used cis,trans (c,t) and trans,cis (t,c) CLA
      isomers to produce CLA-rich eggs, while reports of trans,trans (t,t) CLA
      enrichment in egg yolks are limited. The CLA yolk fatty acid profile changes and
      the 10-12 days of feeding needed for maximum CLA are well documented, but there
      is no information describing CLA accumulation during initial feed administration.
      In addition, no information on CLA accumulation rates in different hen strains is
      available. The aim of this study was to determine a mathematical model that
      described yolk CLA accumulation and depletion in three hen strains by using t,t
      CLA-rich soybean oil produced by photoisomerization. Diets of 30-week Leghorns,
      broilers, and jungle fowl were supplemented with 15% CLA-rich soy oil for 16
      days, and eggs were collected for 32 days. Yolk fatty acid profiles were measured
      by GC-FID. CLA accumulation and depletion was modeled by both quadratic and
      piecewise regression analysis. A strong quadratic model was proposed, but it was
      not as effective as piecewise regression in describing CLA accumulation and
      depletion. Broiler hen eggs contained the greatest concentration of CLA at 3.2
      mol/100 g egg yolk, then jungle fowl at 2.9 mol CLA, and Leghorns at 2.3 mol CLA.
      The t,t CLA isomer levels remained at 55% of total yolk CLA during CLA feeding.
      However, t-10,c-12 (t,c) CLA concentration increased slightly during CLA
      accumulation and was significantly greater than c-9,t-11 CLA. Jungle fowl had the
      smallest increase in yolk saturated fat with CLA yolk accumulation.

PMID- 25771889
TI  - Bone, brain & beyond.
AB  - In the past 15 years, the field of physiology has been radically challenged by
      landmark studies using novel tools of genetic engineering. Particular to our
      interest, the reciprocal interactions between the skeleton and the nervous system
      were shown to be major ones. The demonstration that brain, via multiple pathways,
      is a powerful regulator of bone growth, has shed light on an important central
      regulation of skeletal homeostasis. More recently, it was shown that bone might
      return the favor to the brain through the secretion of a bone-derived hormone,
      osteocalcin. The skeleton influences development and cognitive functions of the
      central nervous system at different stages throughout life suggesting an intimate
      dialogue between bone and brain.

PMID- 25771891
TI  - Essential Fatty Acid Assimilation and Synthesis in Larvae of the Bivalve
      Crassostrea gigas.
AB  - Essential fatty acids (EFA) are important for bivalve larval survival and growth.
      The purpose of this study was to quantitatively assess for the first time through
      a mass-balance approach dietary EFA incorporation and synthesis within
      Crassostrea gigas larvae. A first experiment was carried out using two
      microalgae, Tisochrysis lutea (T) and Chaetoceros neogracile (Cg), as mono- and
      bi-specific diets. A second experiment using a similar design was performed to
      confirm and extend the results obtained in the first. Flow-through larval rearing
      was used for accurate control of food supply and measurement of ingestion. Non
      methylene-interrupted fatty acids were synthetized from precursors supplied in
      the diet: 16:1n-7 and 18:1n-9, mediated by Delta5 desaturase. Moreover, this
      Delta5 desaturase presumably allowed larvae to convert 20:3n-6 and 20:4n-3 to
      20:4n-6 and 20:5n-3, respectively, when the product EFA were poorly or not
      supplied in the diet, as when larvae were fed T exclusively. Under our
      experimental conditions, none of the diets induced 22:6n-3 synthesis; however,
      22:6n-3 incorporation into larval tissues occurred selectively under non-limiting
      dietary supply to maintain optimal levels in the larvae. This combination of flow
      through larval rearing and biochemical analysis of FA levels could be applied to
      additional dietary experiments to precisely define optimal levels of EFA supply. 

PMID- 25771892
TI  - Immunohistochemical localization of basement membrane laminin 5 and collagen IV
      in adult linear IgA disease.
AB  - BACKGROUND: Linear immunoglobulin A disease (LAD), also known as linear IgA
      bullous dermatosis, is an autoimmune disorder characterized by subepidermal
      bullae caused by IgA autoantibodies directed against several antigens located in
      the basement membrane zone of the skin. Laminin 5 (laminin-332) is considered a
      key component of the lamina lucida/lamina densa interface, which provides stable
      attachment of the epidermis to the dermis. Meanwhile, collagen IV is a major
      component of the lamina densa. Laminin 5 and collagen IV bind to the cell
      membrane and induce cytoskeletal rearrangements, which contribute to the basement
      membrane's final mat-like structure. The study aimed to evaluate the
      immunohistochemical staining of laminin 5 and collagen IV and to identify the
      site of blister formation in formalin-fixed, paraffin-embedded skin biopsies from
      adults with LAD. METHODS: Skin biopsies from 20 adult patients with LAD were
      subjected to routine hematoxylin-eosin as well as immunohistochemical staining of
      collagen IV and laminin 5. RESULTS: Linear staining was positive on the floor of
      the blister for laminin 5 in 65% and collagen IV in 90% of biopsies denoting that
      the site of separation in most cases of LAD is above the lamina densa.
      CONCLUSIONS: The use of laminin 5 and collagen IV immunohistochemistry can be
      considered as an adjuvant diagnostic tool and may aid in the identification of
      the site of blister formation in routine skin biopsies in adults with LAD.

PMID- 25771894
TI  - The disease-associated formin INF2/EXC-6 organizes lumen and cell outgrowth
      during tubulogenesis by regulating F-actin and microtubule cytoskeletons.
AB  - We investigate how outgrowth at the basolateral cell membrane is coordinated with
      apical lumen formation in the development of a biological tube by characterizing
      exc-6, a gene required for C. elegans excretory cell (EC) tubulogenesis. We show
      that EXC-6 is orthologous to the human formin INF2, which polymerizes filamentous
      actin (F-actin) and binds microtubules (MTs) in vitro. Dominant INF2 mutations
      cause focal segmental glomerulosclerosis (FSGS), a kidney disease, and
      FSGS+Charcot-Marie-Tooth neuropathy. We show that activated INF2 can substitute
      for EXC-6 in C. elegans and that disease-associated mutations cause constitutive
      activity. Using genetic analysis and live imaging, we show that exc-6 regulates
      MT and F-actin accumulation at EC tips and dynamics of basolateral-localized MTs,
      indicating that EXC-6 organizes F-actin and MT cytoskeletons during
      tubulogenesis. The pathology associated with INF2 mutations is believed to
      reflect misregulation of F-actin, but our results suggest alternative or
      additional mechanisms via effects on MT dynamics.

PMID- 25771893
TI  - Notum is required for neural and head induction via Wnt deacylation, oxidation,
      and inactivation.
AB  - Secreted Wnt morphogens are essential for embryogenesis and homeostasis and
      require a lipid/palmitoleoylate modification for receptor binding and activity.
      Notum is a secreted Wnt antagonist that belongs to the alpha/beta hydrolase
      superfamily, but its mechanism of action and roles in vertebrate embryogenesis
      are not fully understood. Here, we report that Notum hydrolyzes the Wnt
      palmitoleoylate adduct extracellularly, resulting in inactivated Wnt proteins
      that form oxidized oligomers incapable of receptor binding. Thus, Notum is a Wnt
      deacylase, and palmitoleoylation is obligatory for the Wnt structure that
      maintains its active monomeric conformation. Notum is expressed in naive ectoderm
      and neural plate in Xenopus and is required for neural and head induction. These
      findings suggest that Notum is a prerequisite for the "default" neural fate and
      that distinct mechanisms of Wnt inactivation by the Tiki protease in the
      Organizer and the Notum deacylase in presumptive neuroectoderm orchestrate
      vertebrate brain development.

PMID- 25771895
TI  - Hypovitaminosis D and organ damage in patients with arterial hypertension: a
      multicenter double blind randomised controlled trial of cholecalciferol
      supplementation (HYPODD) : study design, clinical procedures and treatment
      protocol.
AB  - INTRODUCTION: At this time, good quality randomized clinical trials assessing the
      effects of vitamin D supplementation on cardiometabolic outcomes are lacking in
      the international literature. AIM: To fill this gap, the Working Group on Vitamin
      D and Cardiorenal Disorders established jointly by the Italian Society of
      Hypertension (SIIA) and the Forum in Bone and Mineral Research conceived the
      HYPODD study (HYPOvitaminosis D and organ Damage). METHODS: HYPODD is a no-profit
      multicenter 12-month parallel-group double-blind placebo controlled randomized
      trial aiming to assess the effects of cholecalciferol supplementation on blood
      pressure control, antihypertensive drugs consumption and progression of target
      organ damage in patients with essential hypertension and 25-hydroxyvitamin D
      serum level lower than 20 ng/ml (vitamin D deficiency). HYPODD is coordinated by
      the European Society Excellence Center of Hypertension of Federico II University,
      Naples, and involves 12 academic institutions in Italy (Ancona, Milan, Padua,
      Perugia, Rome, Siena, Trieste, Turin, Udine, Varese, and Verona). RESULTS AND
      CONCLUSION: The HYPODD study has been registered at the Agenzia Italiana del
      Farmaco-Osservatorio sulla Sperimentazione Clinica del Farmaco (AIFA-OsSC) and
      EUDRACT sites (n degrees  2012-003514-14) and has been approved by the Ethical
      Committees of all the Centers involved in the study. The patients' recruitment is
      currently underway.

PMID- 25771896
TI  - Heparin-engineered mesoporous iron metal-organic framework nanoparticles: toward
      stealth drug nanocarriers.
AB  - The specific modification of the outer surface of the promising porous metal
      organic framework nanocarriers (nanoMOFs) preserving their characteristic
      porosity is still a major challenge. Here a simple, fast, and biofriendly method
      for the external functionalization of the benchmarked mesoporous iron(III)
      trimesate nanoparticles MIL-100(Fe) with heparin, a biopolymer associated with
      longer-blood circulation times is reported. First, the coated nanoparticles
      showed intact crystalline structure and porosity with improved colloidal
      stability under simulated physiological conditions, preserving in addition its
      encapsulation and controlled release capacities. The effect of the heparin
      coating on the nanoMOF interactions with the biological environment is evaluated
      through cell uptake, cytotoxicity, oxidative stress, cytokine production,
      complement activation, and protein adsorption analysis. These results confirmed
      that the heparin coating endowed the nanoMOFs with improved biological
      properties, such as reduced cell recognition, lack of complement activation, and
      reactive oxygen species production. Overall, the ability to coat the surface of
      the nanoMOFs using a simple and straight-forward approach could be taken as a way
      to enhance the versatility and, thus, the potential of porous MOF nanoparticles
      in biomedicine. 

PMID- 25771897
TI  - Indirect electroanalytical detection of phenols.
AB  - A novel indirect electrochemical protocol for the electroanalytical detection of
      phenols is presented for the first time. This methodology is demonstrated with
      the indirect determination of the target analytes phenol, 2-chlorophenol, 4
      chlorophenol and 2,4-dichlorophenol through an electrochemically adapted optical
      protocol. This electrochemical adaptation allows the determination of the above
      mentioned phenols without the use of any oxidising agents, as is the case in the
      optical method, where pyrazoline compounds (mediators) chemically react with the
      target phenols forming a quinoneimine product which is electrochemically active
      providing an indirect analytical signal to measure the target phenol(s). A range
      of commercially available pyrazoline substitution products, namely 4
      dimethylaminoantipyrine, antipyrine, 3-methyl-1-(2-phenylethyl)-2-pyrazolin-5
      one, 3-amino-1-(1-naphthylmethyl)-2-Pyrazolin-5-one, 4-amino-1,2-dimethyl-3
      pentadecyl-3-pyrazolin-5-one hydrochloride, 3-amino-1-(2-amino-4
      methylsulfonylphenyl)-2-pyrazolin-5-one hydrochloride and 4-aminoantipyrine are
      evaluated as mediators for the indirect detection of phenols. The indirect
      electrochemical detection of phenol, 2-chlorophenol, 4-chlorophenol and 2,4
      dichlorophenol through the use of 4-aminoantipyrine as a mediator are
      successfully determined in drinking water samples at analytically useful levels.
      Finally, the comparison of the direct (no mediator) and the proposed indirect
      determination (with 4-aminoantipyrine) towards the analytical detection of the
      target phenols in drinking water is presented. The limitation of the proposed
      electroanalytical protocol is quantified for all the four target phenols. 

PMID- 25771898
TI  - Reply: Takotsubo syndrome-induced acute myocardial infarction.

PMID- 25771899
TI  - Influence of the Molecular Weight and Charge of Antibiotics on Their Release
      Kinetics From Gelatin Nanospheres.
AB  - In this study, we investigated the fundamental relationship between the
      physicochemical characteristics of antibiotics and the kinetics of their release
      from gelatin nanospheres. We observed that antibiotics of high molecular weight
      (colistin and vancomycin) were released in a sustained manner from oppositely
      charged gelatin carriers for more than 14 d, as opposed to antibiotics of low
      molecular weight (gentamicin and moxifloxacin) which were released in a burst
      like manner. The release kinetics of positively charged colistin strongly
      correlated with the rate of the enzymatic degradation of gelatin. To elucidate
      the differences among release kinetics of antibiotics, we explored the mechanism
      of interactions between antibiotics and gelatin nanospheres by monitoring the
      kinetics of release of antibiotics as a function of pH, ionic strength, and
      detergent concentrations. These studies revealed that the interactions between
      antibiotics and gelatin nanospheres were mainly dominated by (i) strong
      electrostatic forces for colistin; (ii) strong hydrophobic and electrostatic
      forces for vancomycin; (iii) weak electrostatic and hydrophobic forces for
      gentamicin; and (iv) weak hydrophobic forces for moxifloxacin. These results
      confirm that release of antibiotics from gelatin nanospheres strongly depends on
      the physicochemical characteristics of the antibiotics. 

PMID- 25771900
TI  - Prognostic significance of TIMP-2, MMP-2, and MMP-9 on high-grade serous ovarian
      carcinoma using digital image analysis.
AB  - The objective of this cohort study was to evaluate whether the
      immunohistochemical expression of tissue inhibitor of metalloprotease 2, matrix
      metalloproteinase (MMP) 2, and MMP-9 could predict the occurrence of death and
      progression in women with ovarian high-grade serous carcinoma (HGSC). A total of
      100 women with primary HGSC who were treated by cytoreductive surgery and
      adjuvant chemotherapy at the Centre Hospitalier Universitaire de Quebec (Canada)
      were included. Biomarker expression was evaluated by immunohistochemistry on
      tissue microarrays constructed from primary tumors. Immunostaining quantification
      was performed using digital image analysis, from algorithms created with Calopix
      software, and continuous H-score data were obtained. The cancer antigen-125
      and/or the Response Evaluation Criteria In Solid Tumors criteria were used to
      define progression. Dates of death were obtained by record linkage with the
      Quebec mortality files. Hazard ratios (HRs) of death and progression with their
      95% confidence intervals (CIs) were estimated using the Cox proportional hazards
      regression model. Overall, a low variability of expression was observed for each
      marker. No association was found between the level of expression and standard
      prognostic factors. When assessed as a continuous variable, increased MMP-9
      expression (10 units of H-score) was associated with death (HR, 1.08; 95% CI,
      1.01-1.16; P = .02), but not with progression (HR, 1.03; 95% CI, 0.97-1.10; P =
      .29). There was no association between the expression of MMP-2 or tissue
      inhibitor of metalloprotease 2 and death or progression. In conclusion, in a
      homogeneous cohort of women with HGSC, increased MMP-9 tissue expression, as
      assessed by automated immunostaining quantification, was associated with a higher
      risk of death. 

PMID- 25771901
TI  - Low expression of olfactomedin 4 correlates with poor prognosis in smoking
      patients with non-small cell lung cancer.
AB  - Olfactomedin 4 (OLFM4) has been demonstrated to serve an important function in
      tumor progression. This study aims to analyze the correlation between OLFM4
      expression and clinicopathological features and the prognostic significance of
      OLFM4 in the context of smoking status of non-small cell lung cancer (NSCLC)
      patients. A total of 218 NSCLC patients, who were histopathologically diagnosed
      from 2001 to 2013, were reviewed in the study. OLFM4 expression was analyzed by
      immunohistochemical staining of tissue samples. The association of OLFM4 with
      clinicopathological parameters was evaluated. Overall survival and disease
      specific survival were evaluated by Kaplan-Meier survival analysis.
      Immunohistochemical analyses showed that OLFM4 was highly expressed in 64.2% of
      NSCLC patients. OLFM4 expression level in NSCLC lesions was strongly correlated
      with pathologic grade (P = .017), lymph node metastasis (P = .012), peritumor
      intravascular cancer emboli (P = .03), and smoking status (P < .001). Kaplan
      Meier survival curves showed that, among smoking patients, those with low OLFM4
      expression had shorter survival time (overall survival and disease-specific
      survival) than those with high OLFM4 (P < .05). Conclusively, although low OLFM4
      expression is not an independent prognostic biomarker, it might indicate worse
      prognosis for smoking patients with NSCLC, thereby identifying patients who might
      benefit from targeting OLFM4 therapy. 

PMID- 25771902
TI  - Immunohistochemical analysis of the expression of cellular transcription NFkappaB
      (p65), AP-1 (c-Fos and c-Jun), and JAK/STAT in leprosy.
AB  - Leprosy is a disease whose clinical spectrum depends on the cytokine patterns
      produced during the early stages of the immune response. The main objective of
      this study was to describe the activation pattern of cellular transcription
      factors and to correlate these factors with the clinical forms of leprosy. Skin
      samples were obtained from 16 patients with the tuberculoid (TT) form and 14 with
      the lepromatous (LL) form. The histologic sections were immunostained with anti-c
      Fos and anti-c-Jun monoclonal antibodies for investigation of AP-1, anti-NFkappaB
      p65 for the study of NFkappaB, and anti-JAK2, STAT1, STAT3, and STAT4 for
      investigation of the JAK/STAT pathway. Cells expressing STAT1 were more frequent
      in the TT form than in LL lesions (P = .0096), in agreement with the protective
      immunity provided by IFN-gamma. STAT4 was also more highly expressed in the TT
      form than in the LL form (P = .0098). This transcription factor is essential for
      the development of a Th1 response because it is associated with interleukin-12.
      NFkappaB (p65) and STAT4 expression in the TT form showed a strong and
      significant correlation (r = 0.7556 and P = .0007). A moderate and significant
      correlation was observed between JAK2 and STAT4 in the TT form (r = 0.6637 and P
      = .0051), with these factors responding to interleukin-12 in Th1 profiles. The
      results suggest that STAT1, JAK2, and NFkappaB, together with STAT4, contribute
      to the development of cell-mediated immunity, which is able to contain the
      proliferation of Mycobacterium leprae. 

PMID- 25771903
TI  - Opportunities for strengthening provider-initiated testing and counselling for
      HIV in Namibia.
AB  - This short report identifies enablers and barriers to the uptake of provider
      initiated testing and counselling for HIV (PITC) in Namibia and identifies key
      opportunities for strengthening this vital aspect of the national HIV response.
      We explored this through facility mapping, register reviews and qualitative
      methods including focus group discussions and in-depth interviews. Four health
      facilities (clinics and hospitals) in two regions were included in the study. We
      identified that PITC in Namibia was largely delivered by lay counsellors
      operating in designated rapid testing rooms located in health facilities and
      found a large number of missed opportunities for HIV testing through this model.
      Nurses did not see it as an integral part of their role, were not aware of HIV
      testing and counselling policy, felt inadequately trained and supported, and
      experienced staffing shortages. Institutional issues also acted as barriers to
      nurses performing or initiating discussions about PITC. Wider dissemination and
      implementation of policy, increasing privacy of consultation spaces and community
      sensitisation are simple measures that represent opportunities for strengthening
      this response and ensuring that symptomatic individuals who are unaware of their
      HIV status do not fall through the net. 

PMID- 25771904
TI  - Evaluation of [(11)C]CB184 for imaging and quantification of TSPO overexpression
      in a rat model of herpes encephalitis.
AB  - PURPOSE: Evaluation of translocator protein (TSPO) overexpression is considered
      an attractive research tool for monitoring neuroinflammation in several
      neurological and psychiatric disorders. [(11)C]PK11195 PET imaging has been
      widely used for this purpose. However, it has a low sensitivity and a poor signal
      to-noise ratio. For these reasons, [(11)C]CB184 was evaluated as a potentially
      more sensitive PET tracer. METHODS: A model of herpes simplex encephalitis (HSE)
      was induced in male Wistar rats. On day 6 or 7 after virus inoculation,
      [(11)C]CB184 PET scans were acquired followed by ex vivo evaluation of
      biodistribution. In addition, [(11)C]CB184 and [(11)C]PK11195 PET scans with
      arterial blood sampling were acquired to generate input for pharmacokinetic
      modelling. Differences between the saline-treated control group and the virus
      treated HSE group were explored using volumes of interest and voxel-based
      analysis. RESULTS: The biodistribution study showed significantly higher
      [(11)C]CB184 uptake in the amygdala, olfactory bulb, medulla, pons and striatum
      (p < 0.05) in HSE rats than in control rats, and the voxel-based analysis showed
      higher bilateral uptake in the pons and medulla (p < 0.05, corrected at the
      cluster level). A high correlation was found between tracer uptake in the
      biodistribution study and on the PET scans (p < 0.001, r (2) = 0.71).
      Pretreatment with 5 mg/kg of unlabelled PK11195 effectively reduced (p < 0.001)
      [(11)C]CB184 uptake in the whole brain. Both, [(11)C]CB184 and [(11)C]PK11195,
      showed similar amounts of metabolites in plasma, and the binding potential (BPND)
      was not significantly different between the HSE rats and the control rats. In HSE
      rats BPND for [(11)C]CB184 was significantly higher (p < 0.05) in the amygdala,
      hypothalamus, medulla, pons and septum than in control rats, whereas higher
      uptake of [(11)C]PK11195 was only detected in the medulla. CONCLUSION:
      [(11)C]CB184 showed nonspecific binding to healthy tissue comparable to that
      observed for [(11)C]PK11195, but it displayed significantly higher specific
      binding in those brain regions affected by the HSE. Our results suggest that
      [(11)C]CB184 PET is a good alternative for imaging of neuroinflammatory
      processes.

PMID- 25771905
TI  - Persistent quality of life impairments in differentiated thyroid cancer patients:
      results from a monitoring programme.
AB  - PURPOSE: Health-related quality of life (HRQOL) in differentiated thyroid cancer
      (DTC) research has so far received little attention and available results are
      conflicting. We studied the HRQOL of radioiodine-naive DTC patients in comparison
      with the general population (GP), investigated the course of HRQOL up to 30
      months after radioiodine remnant ablation (RAA) and sought to identify patient
      characteristics associated with HRQOL. METHODS: We analysed data from routine
      HRQOL monitoring at a nuclear medicine department. Between 2005 and 2013, a total
      of 439 thyroid cancer patients (all histologies) completed the EORTC Quality of
      Life Questionnaire Core-30 (QLQ-C30) at least once during their treatment at the
      department. We compared patients' baseline HRQOL scores before RAA with scores
      from age-matched and sex-matched controls from the Austrian GP. We then
      determined the course of HRQOL over the 30 months after RAA and assessed the
      impact of the following clinical variables on HRQOL: method of thyroid
      stimulating hormone (TSH) stimulation, histology (papillary vs. follicular) and
      disease stage. RESULTS: A total of 284 patients (mean age 48.3 years, SD 15.0
      years; 71.6% women; 80.7% papillary type) with a baseline HRQOL assessment before
      RAA were available. We found clinically meaningful differences in the detriment
      in patients on almost all domains. These were largest for fatigue (23 points) and
      role functioning (25 points). Data from 241 patients (mean age 48.6 years, SD
      15.9 years; 68.9% women; 76.3% papillary type) were included in the longitudinal
      analysis. Investigating the course of HRQOL, a significant improvement over time
      was found for role and emotional functioning, fatigue, pain, and dyspnoea. A
      range of HRQOL scores were improved in patients with exogenous TSH stimulation,
      but some scores both in patients with exogenous TSH stimulation and in those
      followed for 30 months, especially fatigue and role functioning, did not reach
      levels in the GP sample. CONCLUSION: Our results show that the favourable
      prognosis of DTC does not directly translate into good HRQOL in these patients.
      Persistent restrictions in regaining their normal daily life in terms of work and
      leisure highlight the importance of more detailed investigation of DTC patients'
      wellbeing, support needs, and disease experience.

PMID- 25771907
TI  - Defect-mediated modulation of optical properties in vertically aligned ZnO
      nanowires via substrate-assisted Ga incorporation.
AB  - We report the defect-mediated modulation of optical properties in vertically
      aligned ZnO nanowires via a substrate-assisted Ga incorporation method. We find
      that Ga atoms were incorporated into a ZnO lattice via the diffusion of liquid Ga
      droplets from a GaAs substrate in which as-grown ZnO nanowires were placed face
      down on the GaAs substrate and annealed at 650  degrees C. Based on structural
      and compositional characterization, it was confirmed that the substrate-assisted
      incorporation of Ga can induce a high defect density in vertically aligned ZnO
      nanowires grown on a Si substrate. In addition, distinct differences in optical
      properties between as-grown and Ga-incorporated ZnO nanowires were found and
      discussed in terms of defect-mediated modifications of energy band states, which
      were associated with the generation and recombination of photoexcited carriers.
      Furthermore, it was clearly observed that for Ga-incorporated ZnO nanowires, the
      photocurrent rise and decay processes were slower and the photocurrents under UV
      illumination were significantly higher compared with as-grown nanowires. 

PMID- 25771906
TI  - Nuclear imaging of neuroendocrine tumors with unknown primary: why, when and how?
AB  - Neuroendocrine tumors (NETs) with unknown primary (CUP-NET) are associated with a
      poor prognosis (10-year survival 22%), grade 1 and 2 NETs having a more favorable
      outcome than grade 3 (also called carcinoma). There is evidence that an effort
      should be made to localize the primary tumor even in the presence of metastasis
      because resection of the primary tumor(s) may improve disease-free and overall
      survival, and because the choice of chemotherapeutic agent depends on the
      location of the primary tumor. Localization of the tumors remains challenging and
      often relies on a combination of radiological, endoscopic and functional imaging.
      The functional imaging protocol for evaluation of these patients has historically
      relied on somatostatin receptor scintigraphy (SRS). However, the sensitivity and
      specificity of SRS may be unsatisfactory, especially for NETs of midgut origin.
      Newer PET radiotracers such as (68)Ga-labeled somatostatin analogs ((68)Ga-DOTA
      SSTa) and (18)F-DOPA have shown promise. In direct comparisons between (68)Ga
      DOTA-SSTa PET/CT and (99m)Tc-HYNIC-octreotide/(111)In-pentetreotide SPECT(/CT),
      (68)Ga-DOTA-SSTa performed better than other techniques, giving a compelling
      reason for switching from SPECT/CT to PET/CT imaging. (18)F-DOPA performs better
      than SRS and CT in well-differentiated NETs of the small intestine. For detecting
      pancreatic NETs, the high background uptake of (18)F-DOPA by the normal exocrine
      pancreas can be somewhat overcome by pretreatment with carbidopa. We have
      suggested a protocol in which SRS is replaced by one of the two agents
      (preferably with (68)Ga-DOTA-SSTa, alternatively (18)F-DOPA) as first-line
      nuclear tracer for detection of CUP-NET in patients with well-differentiated NETs
      and (18)F-FDG PET/CT may be an additional diagnostic test for poorly
      differentiated tumors and for prognostication. In the near future, it is expected
      that patients with CUP-NET will benefit from newly developed PET approaches
      (radiopharmaceuticals) and intraoperative PET imaging.

PMID- 25771908
TI  - Aroma potential of oak battens prepared from decommissioned oak barrels.
AB  - During barrel maturation, volatile compounds are extracted from oak wood and
      impart aroma and flavor to wine, enhancing its character and complexity. However,
      barrels contain a finite pool of extractable material, which diminishes with
      time. As a consequence, most barrels are decommissioned after 5 or 6 years. This
      study investigated whether or not decommissioned barrels can be "reclaimed" and
      utilized as a previously untapped source of quality oak for wine maturation. Oak
      battens were prepared from staves of decommissioned French and American oak
      barrels, and their composition analyzed before and after toasting. The oak
      lactone glycoconjugate content of untoasted reclaimed oak was determined by
      liquid chromatography-tandem mass spectrometry, while the concentrations of cis-
      and trans-oak lactone, guaiacol, 4-methlyguaiacol, vanillin, eugenol, furfural,
      and 5-methylfurfural present in toasted reclaimed oak were determined by gas
      chromatography-mass spectrometry. Aroma potential was then evaluated by comparing
      the composition of reclaimed oak with that of new oak. Comparable levels of oak
      lactone glycoconjugates and oak volatiles were observed, demonstrating the aroma
      potential of reclaimed oak and therefore its suitability as a raw material for
      alternative oak products, i.e., chips or battens, for the maturation of wine. The
      temperature profiles achieved during toasting were also measured to evaluate the
      viability of any yeast or bacteria present in reclaimed oak. 

PMID- 25771909
TI  - Proximate Context of HIV Stigma and Its Association with HIV Testing in Sierra
      Leone: A Population-Based Study.
AB  - The extent to which HIV stigma at the community level remains a barrier to
      greater uptake in HIV testing services is poorly understood. We used nationally
      representative data from the 2008 Sierra Leone Demographic and Health Survey. The
      primary outcome was HIV testing (past 12 months). Our explanatory variable was
      HIV stigmatizing attitudes (5-item scale). After multivariable adjustment, HIV
      testing had an inverse association with HIV stigmatizing attitudes measured at
      the individual [adjusted odds ratio (AOR) 0.94; 95 % CI 0.87-1.01] and community
      level (AOR 0.70; 95 % CI 0.58-0.85). HIV stigma had a stronger negative
      association with HIV testing when modeled at the community rather than individual
      level.

PMID- 25771910
TI  - Parental Perceptions of the Use of Coercive Measures on Children with
      Developmental Disabilities.
AB  - BACKGROUND: Children with developmental disabilities who exhibit challenging
      behaviour are potentially subject to the use of coercive interventions. The aim
      of the study was to investigate the prevalence of the use of coercive measures by
      authorities, according to parents' reports. MATERIALS AND METHODS: A postal
      survey was distributed, as a total population study, to 946 Finnish parents of
      children with developmental disabilities, between the ages of 5 and 15, and who
      were entitled to the highest disability allowance. RESULTS: Of the respondents,
      54 (22%) answered 'yes' when asked whether their child had been subjected to
      coercive procedures by authorities. The parents had seldom approved the use of
      coercive means and often believed that such means had negative effects on their
      child. CONCLUSIONS: To protect the children's rights, the use of coercive
      measures should be regulated more strictly, and positive intervention strategies
      should be taught to teachers and nurses.

PMID- 25771911
TI  - Strengthening positive coparenting in teen parents: a cultural adaptation of an
      evidence-based intervention.
AB  - Teen childbearing is associated with a range of adverse outcomes for both mothers
      and children, and perpetuates an intergenerational cycle of socioeconomic
      disadvantage. Fathers may be an underappreciated source of support to teen
      mothers and their children. The strongest and most consistent predictor of
      positive father involvement is a positive coparenting relationship between the
      mother and father. Thus, strengthening the coparenting relationship of teen
      parents may be protective for both parents and children. This paper describes the
      rationale, the intervention model, and the cultural adaptation of Strong
      Foundations, an intervention designed to facilitate and enhance positive
      coparenting in teen parents. Adapted from an evidence-based coparenting program
      for adult, cohabiting parents, this intervention was modified to be
      developmentally and culturally appropriate, acceptable, and feasible for use with
      urban, low-income, minority expectant teen mothers and their male partners. The
      authors present lessons learned from the cultural adaptation of this innovative
      intervention. Pilot testing has shown that this model is both acceptable and
      feasible in this traditionally hard to reach population. Although recruitment and
      engagement in this population present specific challenges, young, urban minority
      parents are deeply interested in being effective coparents, and were open to
      learning skills to support this goal. 

PMID- 25771912
TI  - Taking the next step forward - Diagnosing inherited infantile cholestatic
      disorders with next generation sequencing.
AB  - Identifying rare genetic forms of infantile cholestasis is challenging due to
      their similar clinical presentation and their diverse etiology. After exclusion
      of common non-genetic causes a huge list of rare differential diagnosis remains
      to be solved. More than 90 genes are associated with monogenic forms of infantile
      cholestasis, thus preventing routine genetic workup by Sanger sequencing. Here we
      demonstrate a next generation sequencing approach to discover the underlying
      cause in clinically well characterized patients in whom common causes of
      infantile cholestasis have been excluded. After validation of the analytical
      sensitivity massive parallel sequencing was performed for 93 genes in six
      prospectively studied patients. Six novel mutations (PKHD1: p.Thr777Met,
      p.Tyr2260Cys; ABCB11: p.Val1112Phe, c.611+1G > A, p.Gly628Trpfs*3 and NPC1:
      p.Glu391Lys) and two known pathogenic mutations were detected proving our multi
      gene panel for infantile cholestasis to be a sensitive and specific method
      overcoming the complexity of the phenotype-based, candidate gene approach. Three
      exemplary clinical cases of infants with cholestasis are presented and discussed
      in the context of their genetic and histopathological findings (autosomal
      recessive polycystic kidney disease, atypical PFIC and Niemann-Pick syndrome type
      C1). These case reports highlight the critical impact of integrating clinical,
      histopathological and genetic data during the process of multi gene panel testing
      to ultimately pinpoint rare genetic diagnoses.

PMID- 25771913
TI  - Characterization of a novel standardized human three-dimensional skin wound
      healing model using non-sequential fractional ultrapulsed CO2 laser treatments.
AB  - BACKGROUND AND OBJECTIVE: At present, there is no standardized in vitro human
      skin model for wound healing. Therefore, our aim was to establish and
      characterize an in vitro/ex vivo three-dimensional (3D) wound healing model,
      which we employed to analyze the effects of dexpanthenol on wound healing and
      gene regulation. MATERIALS AND METHODS: The novel human 3D skin wound healing
      model using scaffold and collagen 3D organotypic skin equivalents was irradiated
      with a non-sequential fractional ultrapulsed CO2 laser. These standardized
      injured full-thickness skin equivalents enable qRT-PCR, microarray, and
      histological studies analyzing the effect of topically or systemically applied
      compounds on skin wound healing. RESULTS: These human laser-irradiated skin
      models were found to be appropriate for in vitro wound healing analysis. Topical
      treatment of skin wounds with a 5% dexpanthenol water-in-oil emulsion or two
      different 5% dexpanthenol oil-in-water emulsions clearly enhanced wound closure
      compared to laser-irradiated untreated control models. To find out whether this
      positive effect is caused by the active substance dexpanthenol, laser-irradiated
      skin models were cultured in calciumpantothenate containing medium (20 MUg/ml)
      compared to skin equivalents cultured without calciumpantothenate. 3D models
      cultured in calciumpantothenate revealed considerably faster wound closure
      compared to the control models. Quantitative RT-PCR studies showed enhanced mRNA
      expression of MMP3, IL1alpha, keratin-associated protein 4-12 (KRTAP4-12), and
      decreased expression of S100A7 in laser-irradiated skin models cultured in medium
      containing calciumpantothenate. CONCLUSION: This novel standardized human 3D skin
      wound healing model proves useful for topical pharmacological studies on wound
      healing and reveals new insights into molecular mechanisms of dexpanthenol
      mediated effects on wound healing. In addition, these novel 3D model systems can
      be used to monitor ex vivo effects of various laser systems on gene expression
      and morphology of human skin.

PMID- 25771914
TI  - Indices of bipolar complex fractionated atrial electrograms correlate poorly with
      each other and atrial fibrillation substrate complexity.
AB  - BACKGROUND: The pathophysiological relevance of complex fractionated atrial
      electrograms (CFAE) in atrial fibrillation (AF) remains poorly understood.
      OBJECTIVE: The aim of this study was to comprehensively investigate how bipolar
      CFAE correlates with unipolar electrogram fractionation and the underlying
      electrophysiological substrate of AF. METHODS: Ten-second unipolar AF
      electrograms were recorded using a high-density electrode from the left atrium of
      20 patients with AF (10 with persistent AF and 10 with paroxysmal AF) undergoing
      cardiac surgery. Semiautomated bipolar CFAE algorithms: complex fractionated
      electrogram-mean, interval confidence interval, continuous electrical activity,
      average complex interval, and shortest complex interval were evaluated against AF
      substrate complexity measures following fibrillation wave reconstruction derived
      from local unipolar activation time. The effect of interelectrode spacing and
      electrode orientation on bipolar CFAE was also examined. RESULTS: All 5
      semiautomated bipolar CFAE algorithms showed poor correlation with each other and
      AF substrate complexity measures (conduction velocity, number of waves or
      breakthroughs per AF cycle, and electrical dissociation). Bipolar CFAE also
      correlated poorly with fractionation index derived from unipolar electrograms.
      Increased interelectrode spacing resulted in an increase in bipolar CFAE detected
      except for the interval confidence interval algorithm. CFAE appears unaffected by
      bipolar electrode orientation (vertical vs horizontal). By contrast, unipolar
      fractionation index correlated well with AF substrate complexity measures and can
      be regarded as a marker for conduction block. CONCLUSION: The lack of
      pathophysiological relevance of bipolar CFAE analysis may in part contribute to
      the divergent and limited success rates of catheter ablation strategies targeting
      CFAE.

PMID- 25771915
TI  - More about adolescent competitive swimming.

PMID- 25771916
TI  - Reply: To PMID 25444007.

PMID- 25771917
TI  - Lymph node flap transfer for patients with secondary lower limb lymphedema.
AB  - BACKGROUND: Previous authors have shown benefits from the use of lymph node flap
      transfer (LNFT) to treat lymphedema of the arms, but there is little evidence for
      its use for lower limb lymphedema. We performed a retrospective analysis of a
      series of patients suffering from secondary lower limb lymphedema treated with a
      free LNFT. METHODS: 52 cases of LNFT to treat 41 legs in 38 patients with
      secondary lymphedema were retrospectively reviewed. The causes of the lymphedema
      included lymphedema secondary to hysterectomy for uterine cancer, melanoma
      resections on the leg, lymphoma treatment and testicular cancer, cosmetic surgery
      to the limb, lipoma resection at the inguinal region, and a saphenectomy.
      Patients had been suffering with lymphedema for an average of 9.1 +/- 7.3 years
      at the time of LNFT. RESULTS: Eleven patients (28.9%) presented with minor
      complications treated conservatively. For 23 legs there was enough data to follow
      limb volume evolution after a single LNFT. Total volume reduction in eight legs
      (two patients with no measures of the healthy limb and three bilateral) was 7.1
      +/- 8.6%. Another group of 15 patients with unilateral lymphedema had an average
      46.3 +/- 34.7% reduction of excess volume. Better results (>30% REV) were
      associated with smaller preoperative excess volume (P = 0.045). CONCLUSION:
      Patients with secondary leg lymphedema can benefit from LNFT. Results in patients
      with mild presentations seem to be better than in more severe cases. (c) 2014
      Wiley Periodicals, Inc. Microsurgery 37:29-33, 2017.

PMID- 25771918
TI  - MITIGATION OF Cu(II) PHYTOTOXICITY TO RICE (ORYZA SATIVA) IN THE PRESENCE OF TiO2
      AND CeO2 NANOPARTICLES COMBINED WITH HUMIC ACID.
AB  - Engineered nanoparticles (NPs) and natural organic matter (NOM) in the
      environment may interact with background contaminants such as heavy metals and
      modify their bioavailability and toxicity. In the present study, the combined
      influences of 2 common NPs (TiO2 and CeO2 ) and humic acid (HA; as a model NOM)
      on Cu(II) phytotoxicity to rice were investigated by a 3-d root elongation assay
      performed on filter paper media. The results showed that the adsorption
      coefficients of bare TiO2 and CeO2 NPs (100 mg/L) toward Cu(2+) are 2.65 and
      4.37, respectively, at an initial concentration of 10 mg/L, suggesting that
      Cu(II) could be strongly adsorbed by NPs, whereas HA-coated TiO2 and CeO2 NPs
      further enhanced the adsorption coefficients to 4.37 and 6.85, respectively. In
      addition, compared with Cu-alone treatment, the addition of bare TiO2 and CeO2
      NPs (1000 mg/L) increased the length of rice root by 32.5% and 39.0%,
      respectively; however, the presence of HA-coated TiO2 and CeO2 NPs increased the
      root length by 90.2% and 100.1%, respectively, which indicated that the
      mitigation effect of HA-coated NPs on Cu(II) phytotoxicity was more visible than
      that of bare NPs. The results demonstrated that coexistence of NPs and HA
      significantly alleviated Cu(II) phytotoxicity as a result of a decrease in
      bioavailable soluble Cu(II) concentration, which contributes to an understanding
      of the potential behavior of NPs in the environment.

PMID- 25771919
TI  - Direct evidence of anomalous interfacial magnetization in metamagnetic Pd doped
      FeRh thin films.
AB  - Palladium doped iron rhodium is a magnetic material of significant interest for
      it's close to room temperature magnetostructural phase transition from
      antiferromagnetic (AF) to ferromagnetic (FM) ordering. Here we report on the
      peculiarities of the magnetization distribution in thin films of FeRh(Pd) probed
      by Polarized Neutron Reflectometry. Remarkably, we've found thin interfacial
      regions with strong magnetization that have unique thermomagnetic properties as
      compared to the rest of the system. These regions exist at the top and bottom
      interfaces of the films while the central regions behave similarly to the bulk
      with a clear AF-FM order transition. Further we explore the impact of an
      additional Pt interlayer introduced in the middle of the FeRh(Pd) film and reveal
      that it serves to replicate the strong interfacial magnetization found at the top
      and bottom interfaces. These results are of great value both in understanding the
      fundamental physics of such an order transition, and in considering FeRh(Pd) for
      magnetic media and spintronics applications. 

PMID- 25771920
TI  - Neuraxial blockade for external cephalic version: Cost analysis.
AB  - AIM: Neuraxial blockade (epidural or spinal anesthesia/analgesia) with external
      cephalic version increases the external cephalic version success rate. Hospitals
      and insurers may affect access to neuraxial blockade for external cephalic
      version, but the costs to these institutions remain largely unstudied. The
      objective of this study was to perform a cost analysis of neuraxial blockade use
      during external cephalic version from hospital and insurance payer perspectives.
      Secondarily, we estimated the effect of neuraxial blockade on cesarean delivery
      rates. METHODS: A decision-analysis model was developed using costs and
      probabilities occurring prenatally through the delivery hospital admission. Model
      inputs were derived from the literature, national databases, and local supply
      costs. Univariate and bivariate sensitivity analyses and Monte Carlo simulations
      were performed to assess model robustness. RESULTS: Neuraxial blockade was cost
      saving to both hospitals ($30 per delivery) and insurers ($539 per delivery)
      using baseline estimates. From both perspectives, however, the model was
      sensitive to multiple variables. Monte Carlo simulation indicated neuraxial
      blockade to be more costly in approximately 50% of scenarios. The model
      demonstrated that routine use of neuraxial blockade during external cephalic
      version, compared to no neuraxial blockade, prevented 17 cesarean deliveries for
      every 100 external cephalic versions attempted. CONCLUSIONS: Neuraxial blockade
      is associated with minimal hospital and insurer cost changes in the setting of
      external cephalic version, while reducing the cesarean delivery rate.

PMID- 25771921
TI  - Second-stage transsphenoidal approach (TSA) for highly vascular pituicytomas in
      children.
AB  - INTRODUCTION: A pituicytoma in the sellar area is extremely rare in children and,
      due to its highly vascularized nature, can be difficult to address using the
      transsphenoid approach (TSA) to surgery. Here, we report a rare case of a
      pituicytoma that was completely removed from a child through a staged operation
      using the TSA. A 13-year-old girl was admitted with a 1-year history of visual
      disturbance and amenorrhea. Visual field examination showed left total blindness
      and right temporal hemianopsia. Laboratory results revealed hormonal levels all
      within normal ranges. Brain magnetic resonance imaging (MRI) showed a
      homogeneous, highly enhancing sellar and suprasellar mass, typically suggestive
      of a pituitary adenoma. TSA surgery revealed the tumor had a rubbery-firm
      consistency, hypervascularity, and profuse bleeding. We removed the tumor
      partially and planned a second-stage operation. DISCUSSION: Gross total removal
      is the treatment of choice for this type of tumor. Attempted resection of these
      presumed adenomas or meningiomas using the TSA often results in unexpectedly
      heavy intraoperative bleeding due to the high vascularity of this rare tumor,
      making surgery challenging, especially in children where the tumor is within a
      relatively narrow corridor. While pituicytomas are a rare differential diagnosis
      for sellar or parasellar tumors in children, total removal by second-stage TSA
      surgery is indicated in the case of profuse bleeding or uncertainty of biopsy.
      Following first-stage TSA surgery and pathologic confirmation of pituicytoma, the
      strategy is typically gross total removal during second-stage TSA surgery.
      CONCLUSIONS: Although very rare in children, a pituicytoma should be included in
      the differential diagnosis of a mass in the sellar area if the tumor is highly
      enhancing or very vascular. Second-stage TSA surgery is another strategy when the
      pathology is not clear during the first-stage TSA surgery.

PMID- 25771922
TI  - Three-dimensional analysis of cranial and facial asymmetry after helmet therapy
      for positional plagiocephaly.
AB  - PURPOSE: Helmet therapy is a non-surgical option for treating positional
      plagiocephaly, and its effectiveness has been validated by various researches. In
      addition to cranial flattening and asymmetry, ipsilateral prominence of the mid
      face and relative anterior transposition of the ipsilateral ear is also common.
      Hence, we investigated the impact of helmet therapy on mid-facial asymmetry.
      METHODS: Ninety-nine patients diagnosed with positional plagiocephaly and treated
      by helmet therapy between September 2005 and July 2012 were enrolled. Therapy was
      initiated at various ages: group I, <6 months (n = 35); group II, 6 months to 1
      year (n = 43); group III, >1 year (n = 21). A cranial vault asymmetry index was
      measured at the levels of the inferior orbital rim (CVAIIOR-MF) and superior
      orbital rim (CVAISOR-LC) and midway from the superior orbital rim to the vertex
      (CVAIMID-UC). Anterior transposition of the ipsilateral ear was verified by
      measuring the distance (D EAR) between the actual position of the ear and its
      expected position relative to the contralateral ear. All variables were compared
      before and after helmet therapy and were categorized by age at treatment
      initiation. RESULTS: CVAIIOR-MF and CVAISOR-LC were lower in all three age groups
      after helmet therapy, confirming therapeutic efficacy. CVAIMID-UC (upper level
      cranial asymmetry) and D EAR (mid-facial soft tissue asymmetry) also improved
      significantly in groups I and II which were younger than 1 year old. CONCLUSION:
      In positional plagiocephaly, helmet therapy is effective in correcting both
      cranial and mid-facial asymmetries. Outcomes were optimal in patients <1 year of
      age, but older patients also showed some improvement.

PMID- 25771923
TI  - Prolactinomas in children under 14. Clinical presentation and long-term follow
      up.
AB  - PURPOSE: Pediatric prolactinomas are rare, especially in children under 14 years
      of age. In this study, we evaluated the clinical presentation and microsurgical
      outcome of prolactinomas in prepubertal children. METHODS: Nine patients with
      prolactinomas who had undergone surgical removal of the tumor before the age of
      14 years were included in this retrospective study. Data on their clinical
      presentation, medications, physical and laboratory evaluations, radiological
      findings, and long-time follow-up were obtained from their medical records.
      RESULTS: The main presenting symptom in the four female patients was galactorrhea
      (n = 4, 100%), whereas the five male patients most commonly presented with
      headache (n = 4, 80%) and growth retardation (n = 3, 60%). Six (66.6%) of the
      patients who had undergone transsphenoidal surgery were medication-free
      postoperatively. In three (33.3%) patients with giant adenomas, complete
      resection of the tumor was not achieved. One (11.1%) patient received
      radiotherapy after failed surgical and medical treatment. Postoperatively,
      electrolyte disturbances occurred in five (55.6%) patients, diabetes insipidus in
      two (22.2%), and thyroid dysfunction in two (22.2%). These complications resolved
      spontaneously. During follow-up, growth and puberty were usually normal.
      CONCLUSIONS: Tumor compressive symptoms and/or gonadal and growth arrest may be
      the primary clinical presentations of pediatric prolactinoma. Patients who are
      not candidates for dopamine agonist therapy are best treated surgically, based on
      the low mortality and high cure rates. Hypopituitarism is a rare complication and
      may resolve spontaneously. Following successful treatment of a prolactinoma,
      growth and puberty in these children are normal.

PMID- 25771924
TI  - Hypertrophic pachymeningitis.
AB  - BACKGROUND: Hypertrophic pachymeningitis (HP) is a rare clinical entity
      characterized by diffuse or localized fibrous thickening of the dura mater. It is
      well known but rare especially in pediatric population disease of differing
      origins. The primary (idiopathic) form is diagnosed after excluding other
      possible etiologies. Similar results from magnetic resonance imaging (MRI) for
      patients with hypertrophic pachymeningitis and meningiomas may make the diagnosis
      confusing. Additionally, making a proper diagnosis without histological sampling
      can be difficult in some cases. CASE DESCRIPTION: We present a case of an 18-year
      old boy diagnosed with hypertrophic pachymeningitis in the area of the
      hypoglossal canal. The diagnosis was made after a 2-month history of hypoglossal
      nerve palsy and dysphagia preceded by a middle ear infection. The patient was
      treated surgically with suspicion of meningioma, but no evidence of a tumor was
      found during the operation. The postoperative period was uneventful. At the
      latest check-up, MRI revealed regression of all previously observed pathological
      changes.

PMID- 25771925
TI  - Osteoblast biocompatibility of premineralized, hexamethylene-1,6
      diaminocarboxysulfonate crosslinked chitosan fibers.
AB  - Biopolymer-ceramic composites are thought to be particularly promising materials
      for bone tissue engineering as they more closely mimic natural bone. Here, we
      demonstrate the fabrication by electrospinning of fibrous chitosan-hydroxyapatite
      composite scaffolds with low (1 wt %) and high (10 wt %) mineral contents.
      Scanning electron microscopy (FESEM), energy dispersive spectroscopy (EDS) and
      unidirectional tensile testing were performed to determine fiber surface
      morphology, elemental composition, and tensile Young's modulus (E) and ultimate
      tensile strength (sigmaUTS ), respectively. EDS scans of the scaffolds indicated
      that the fibers, crosslinked with either hexamethylene-1,6
      diaminocarboxysulfonate (HDACS) or genipin, have a crystalline hydroxyapatite
      mineral content at 10 wt % additive. Moreover, FESEM micrographs showed that all
      electrospun fibers have diameters (122-249 nm), which fall within the range of
      those of fibrous collagen found in the extracellular matrix of bone. Young's
      modulus and ultimate tensile strength of the various crosslinked composite
      compositions were in the range of 116-329 MPa and 2-15 MPa, respectively.
      Osteocytes seeded onto the mineralized fibers were able to demonstrate good
      biocompatibility enhancing the potential use for this material in future bone
      tissue engineering applications.

PMID- 25771926
TI  - Novel lipidized analogs of prolactin-releasing peptide have prolonged half-lives
      and exert anti-obesity effects after peripheral administration.
AB  - OBJECTIVES: Obesity is a frequent metabolic disorder but an effective therapy is
      still scarce. Anorexigenic neuropeptides produced and acting in the brain have
      the potential to decrease food intake and ameliorate obesity but are ineffective
      after peripheral application. We have designed lipidized analogs of prolactin
      releasing peptide (PrRP), which is involved in energy balance regulation as
      demonstrated by obesity phenotypes of both PrRP- and PrRP-receptor-knockout mice.
      RESULTS: Lipidized PrRP analogs showed binding affinity and signaling in PrRP
      receptor-expressing cells similar to natural PrRP. Moreover, these analogs showed
      high binding affinity also to anorexigenic neuropeptide FF-2 receptor. Peripheral
      administration of myristoylated and palmitoylated PrRP analogs to fasted mice
      induced strong and long-lasting anorexigenic effects and neuronal activation in
      the brain areas involved in food intake regulation. Two-week-long subcutaneous
      administration of palmitoylated PrRP31 and myristoylated PrRP20 lowered food
      intake, body weight and improved metabolic parameters, and attenuated lipogenesis
      in mice with diet-induced obesity. CONCLUSIONS: Our data suggest that the
      lipidization of PrRP enhances stability and mediates its effect in central
      nervous system. Strong anorexigenic and body-weight-reducing effects make
      lipidized PrRP an attractive candidate for anti-obesity treatment.

PMID- 25771927
TI  - CD28 deletion improves obesity-induced liver steatosis but increases adiposity in
      mice.
AB  - BACKGROUND/OBJECTIVES: Lymphocytes have a critical role in visceral adipose
      tissue (AT) inflammation. The CD28 costimulatory molecule is required for
      lymphocyte activation and for the development of a functional regulatory T cells
      (Tregs) compartment; however, its role during obesity is unknown. METHODS: During
      diet-induced obesity, we investigated the effects of selective interference with
      CD28 signaling using knockout mice (Cd28KO) and a CTLA4-Ig fusion protein
      inhibiting CD28-B7 interactions. RESULTS: Cd28 deficiency decreased pathogenic T
      cells and Treg content within AT without changing the macrophages number. Cd28KO
      epididymal but not subcutaneous fat was characterized by enlarged adipocytes,
      reduced levels of inflammatory cytokines and increased Glut4, adiponectin and
      lipogenic enzyme mRNA levels. This was associated with reduced inflammation, fat
      accumulation and enhanced glucose metabolism in liver. Weight gain and fasting
      glucose tolerance were not affected. CTLA4-Ig injections reduced the number of T
      cells in epididymal AT (epiAT) but not the inflammatory cytokines levels and
      failed to improve liver fat accumulation. CONCLUSIONS: Deletion of CD28 creates a
      new pro/anti-inflammatory balance in epiAT and liver and exerts a protective
      effect against hepatic steatosis.

PMID- 25771928
TI  - Trends in body mass index according to educational attainment for urban
      Australian adults between 1980 and 2007.
AB  - BACKGROUND: We have previously demonstrated that between the years 1980 and 2000,
      the mean body mass index (BMI) of the urban Australian population increased, with
      greater increases observed with increasing BMI. The current study aimed to
      quantify trends over time in BMI according to level of education between 1980 and
      2007. METHODS: We compared data from the 1980, 1983 and 1989 National Heart
      Foundation Risk Factor Prevalence Studies, 1995 National Nutrition Survey, 2000
      Australian Diabetes, Obesity and Lifestyle Study and the 2007 National Health
      Survey. For survey comparability, analyses were restricted to urban Australian
      residents aged 25-64 years. BMI was calculated from measured height and weight.
      The education variable was dichotomised at completion of secondary school. Four
      age-standardised BMI indicators were compared over time by sex and education:
      mean BMI, mean BMI of the top 5% of the BMI distribution, prevalence of obesity
      (BMI?30 kg m(-)(2)), prevalence of class II(+) obesity (BMI?35 kg m(-)(2)).
      RESULTS: Between 1980 and 2007, the mean BMI among men increased by 2.5 and 1.7
      kg m(-)(2) for those with low and high education levels, respectively,
      corresponding to increases in obesity prevalence of 20 (from 12-32%) and 11 (10
      21%) %-points. Among women, mean BMI increased by 2.9 and 2.4 kg m(-)(2) for
      those with low and high education levels, respectively, corresponding to
      increases in obesity prevalence of 16 (12-28%) and 12 (7-19%) %-points. The
      prevalence of class II(+) obesity among men increased by 9 (1-10%) and 4 (1-5%) %
      points for those with low and high education levels, and among women increased by
      8 (4-12%) and 4 (2-6%) %-points. Absolute and relative differences between
      education groups generally increased over time. CONCLUSIONS: Educational
      differences in BMI have persisted among urban Australian adults since 1980
      without improvement. Obesity prevention policies will need to be effective in
      those with greatest socio-economic disadvantage if we are to equitably and
      effectively address the population burden of obesity and its corollaries.

PMID- 25771929
TI  - Even transient rapid infancy weight gain is associated with higher BMI in young
      adults and earlier menarche.
AB  - BACKGROUND: Early postnatal rapid 'catch-up' weight gain has been consistently
      associated with subsequent higher obesity risk and earlier pubertal development.
      In many low- and middle-income countries, infancy catch-up weight gain is
      transient and often followed by growth faltering. We explored the hypothesis that
      even transient catch-up weight gain during infancy is associated with later
      obesity risk and earlier puberty. METHODS: A total of 2352 (1151 male, 1201
      female) black South African children in the birth to twenty prospective birth
      cohort study (Johannesburg-Soweto) underwent serial measurements of body size and
      composition from birth to 18 years of age. At the age of 18 years, whole-body fat
      mass and fat-free mass were determined using dual-energy X-ray absorptiometry.
      Pubertal development was assessed by the research team between ages 9 and 10
      years, and it was recorded annually from the age of 11 years using a validated
      self-assessment protocol. RESULTS: Catch-up weight gain from birth to the age of
      1 year, despite being followed by growth faltering between ages 1 and 2 years,
      was associated with greater mid-upper arm circumference (P=0.04) and skinfold
      thickness (P=0.048) at 8 years of age, and with higher weight (P<0.001) and body
      mass index (P=0.001) at 18 years of age after adjustment for sex, age, smoking
      during pregnancy, birth order, gestational age, formula-milk feeding and
      household socio-economic status. Infancy catch-up weight gain was also associated
      with younger age at menarche in girls (P<0.001). This association persisted after
      adjustment for smoking during pregnancy, birth order, gestational age, formula
      milk feeding and household socio-economic status (P=0.005). CONCLUSION: Transient
      catch-up weight gain from birth to the age of 1 year among children born in a low
      income area of South Africa was associated with earlier menarche and greater
      adiposity in early adulthood. This observation suggests that modifiable
      determinants of rapid infancy weight gain may be targeted in order to prevent
      later obesity and consequences of earlier puberty in girls.

PMID- 25771930
TI  - Fasting substrate oxidation at rest assessed by indirect calorimetry: is prior
      dietary macronutrient level and composition a confounder?
AB  - Indirect calorimetry, the measurement of O2 consumption and CO2 production,
      constitutes an invaluable tool as the most common method for analyzing whole-body
      energy expenditure, and also provides an index of the nature of macronutrient
      substrate oxidation--namely, carbohydrate (CHO) versus fat oxidation. The latter
      constitutes a key etiological factor in obesity as this condition can only
      develop when total fat oxidation is chronically lower than total exogenous fat
      intake. The standardization of indirect calorimetry measurements is essential for
      accurately tracking the relative proportion of energy expenditure derived from
      CHO and fat oxidation. Here we analyze literature data to show that the average
      fasting respiratory quotient typically shifts from approximately 0.80 to 0.90
      (indicating a doubling of resting CHO oxidation) in response to a switch in
      dietary CHO intake (as % energy) from 30 to 60%. This underscores the importance
      of taking into account dietary macronutrient composition prior to indirect
      calorimetry studies in the interpretation of data on substrate utilization and
      oxidation.

PMID- 25771931
TI  - High prevalence of fasciolosis and evaluation of drug efficacy against Fasciola
      hepatica in dairy cattle in the Maffra and Bairnsdale districts of Gippsland,
      Victoria, Australia.
AB  - Liver fluke (Fasciola hepatica) is a common parasite amongst grazing livestock in
      the south-eastern region of Australia and is responsible for significant
      production losses in the beef and dairy industries. Gippsland in Victoria is a
      major region for dairy production but no fluke prevalence data in livestock has
      been obtained in this region since the late 1970s prior to the introduction of
      Triclabendazole (TCBZ). TCBZ resistance is also now widespread in cattle in south
      east Australia. In this study, we evaluated the prevalence and intensity of liver
      fluke infections in dairy cattle in Gippsland and assessed the efficacy of TCBZ
      and other drenches against F. hepatica on one farm. We obtained 30 individual
      faecal samples from each of 15 different farms and, using the liver fluke
      coproantigen ELISA, tested bulk faecal samples pooled from each farm. Any farm
      that returned a positive bulk sample had all of the samples tested individually
      to assess the intra-herd prevalence. One farm in the Maffra district also had a
      coproantigen reduction test and faecal egg count reduction test to assess the
      efficacy of TCBZ, Clorsulon (CLOR) and Oxyclozanide (OXY). The coproantigen ELISA
      proved to be a highly sensitive test for liver fluke with a high correlation
      (R(2)=0.8849) observed between ELISA data from bulk samples and individual
      samples, suggesting that future larger scale screening on farms for fasciolosis
      could use the bulk analysis technique. The ELISA data revealed that animals on
      six of the 15 farms were infected with F. hepatica and the herd prevalence of the
      infected herds ranged from 47 to 100% (mean 81%) which exceeds the prevalence
      value for production losses of 25%. The intensity of fluke infection in cattle
      varied considerably both within and between herds with a proportion of animals
      exhibiting a positive control value in the coproantigen ELISA of 50-88%. We also
      confirmed that TCBZ resistance was present on one farm but that CLOR or OXY can
      be used to remove the adult stage of the TCBZ-resistant parasites. We conclude
      that fasciolosis is a significant disease and a likely cause of production losses
      in dairy cattle in the irrigation zones of Gippsland and that TCBZ resistance is
      a serious threat to fluke control. We suggest that more work needs to be
      performed in Gippsland to further define the extent of fasciolosis and drug
      resistance and to ensure that effective chemical and non-chemical methods of
      fluke control are incorporated on farms in order to improve animal welfare and
      reduce financial impacts on producers. 

PMID- 25771932
TI  - Efficacy of entomopathogenic fungi (Ascomycetes: Hypocreales) against adult
      Haematobia irritans (Diptera: Muscidae) under stable conditions in the Mexican
      dry tropics.
AB  - The purpose of this paper is to evaluate the effect of five strains of
      Metarhizium anisopliae (Ma) and three strains of Isaria fumosorosea (Ifr) at a
      concentration of 1*10(8)colony-forming units/ml applied by spraying onto bovines
      with controlled infestation of Haematobia irritans under stable conditions in the
      Mexican dry tropics. Four experiments were performed, in each of which three
      treatments (two fungal strains and one control) were evaluated with eight
      repetitions for each one, by carrying out a single application of the aqueous
      suspension of each strain. The animals were isolated in individual cages and
      direct counts of the infestation were carried out for 13 days. It was observed
      that strains Ma2, Ma6, Ma10, Ma14, and Ma34 caused 94-100% reduction in
      infestation between days 12 and 13 post-treatment, while strains Ifr19, Ifr11,
      and Ifr12 reduced infestation from 90% to 98% up to day 13 post-application.
      There was an effect in the generation of horn flies from the excrement of bovines
      that were treated with different strains, reducing the reproduction of subsequent
      generations. It was concluded that the strains of M. anisopliae and I.
      fumosorosea evaluated in this study can be used as biocontrol agents in
      infestations of H. irritans in stabled bovines.

PMID- 25771933
TI  - Unexpected finding of feline-specific Giardia duodenalis assemblage F and
      Cryptosporidium felis in asymptomatic adult cattle in Northern Spain.
AB  - Giardia duodenalis and Cryptosporidium spp. are common enteric protozoan
      parasites in production animals, including cattle. Typically, both the clinical
      outcome of these infections and the distribution of G. duodenalis assemblages and
      Cryptosporidium species are age-dependent, with the occurrence of diarrhoeal
      disease being mainly associated with young animals and sub-clinical, low
      intensity infections being predominantly found in adult animals. To investigate
      the prevalence and genetic diversity of G. duodenalis and Cryptosporidium spp. in
      asymptomatic adult cattle, a total of 362 faecal samples were collected in four
      farms in the province of Alava, Northern Spain, between November 2011 and
      December 2012. The presence of G. duodenalis was estimated by real-time PCR, and
      the assemblages were determined by multilocus sequence-based genotyping of the
      glutamate dehydrogenase and beta-giardin genes of the parasite. Detection and
      identification of Cryptosporidium species was carried out by sequencing of a
      partial fragment of the small-subunit ribosomal RNA gene. Overall, G. duodenalis
      and Cryptosporidium spp. were detected in 68 (18.8%) and 45 (12.4%),
      respectively, of the 362 animals tested. Strikingly, four isolates representing
      two novel sub-types of G. duodenalis assemblage F were identified at the gdh, but
      not the bg, locus. This is the first report describing the presence of the feline
      specific G. duodenalis assemblage F in bovine isolates. Additionally, five (three
      novel and two known) sub-types of G. duodenalis assemblage E were also identified
      at the gdh locus and a single one (assigned to sub-assemblage EII) at the bg
      locus. Of nine Cryptosporidium isolates, four (including a novel sub-type) were
      assigned to the cat-specific C. felis, two were typed as C. bovis, and the
      remaining three were only characterized at the genus level. Data presented here
      provide epidemiological and molecular evidence demonstrating that the host range
      specificity of G. duodenalis assemblages and Cryptosporidium species may be wider
      than previously anticipated. 

PMID- 25771934
TI  - A molecular and parasitological survey of Hepatozoon canis in domestic dogs in
      Turkey.
AB  - In this study, asymptomatic dogs in nine provinces of Turkey were surveyed to
      investigate the prevalence and intensity of Hepatozoon canis infection. DNA
      obtained from blood samples collected from 694 domestic dogs (243 stray, 288
      shelter, and 163 pets) of both genders and varying ages were evaluated by
      polymerase chain reaction (PCR). In addition, 285 thin blood smears prepared from
      these blood samples were also evaluated for microscopic examination. Direct
      microscopy revealed Hepatozoon gamonts in the peripheral blood of three of 285
      (1.0%; 95% confidence interval (CI): 0.21-3.04) tested. Using PCR, 155 of the 694
      (22.3%; 95% CI: 19.28-25.61) were found to be positive for the presence of H.
      canis DNA. The prevalence of infection was higher in adult dogs (26.2%; 95% CI:
      22.1-30.7) than young animals (16.4%; 95% CI: 12.2-21.3). Although the prevalence
      determined by PCR was higher in male dogs (24.5%; 95% CI: 19.6-29.9) than in
      female dogs (20.8%; 95% CI: 16.9-25.1), gender differences were not significant.
      Pet dogs had a lower prevalence of infection (10.4%; 95% CI: 6.2-16.2) compared
      to stray (26.3%; 95% CI: 20.9-32.3) and shelter dogs (25.7%; 95% CI: 20.7-31.1),
      but no significant association between stray and shelter dogs was found for the
      presence of the parasite. Partial sequences of the 18S ribosomal RNA (rRNA) gene
      shared 99-100% similarity with the corresponding H. canis isolates. This
      epidemiological survey revealed a high prevalence of H. canis in dogs from
      several provinces in Turkey, and it suggests that the age and origin are
      associated with the parasite. 

PMID- 25771935
TI  - Brain-derived neurotrophic factor and substrate utilization following acute
      aerobic exercise in obese individuals.
AB  - Brain-derived neurotrophic factor (BDNF) serves as a vital regulator of neuronal
      proliferation and survival, and has been shown to regulate energy homeostasis,
      glucose metabolism and body weight maintenance. Elevated concentrations of plasma
      BDNF have been associated with obesity and type 2 diabetes mellitus. Acute
      aerobic exercise transiently increases circulating BDNF, potentially correcting
      obesity-related metabolic impairment. The present study aimed to compare acute
      aerobic exercise elicited BDNF responses in obese and normal-weight subjects.
      Furthermore, we aimed to investigate whether acute exercise-induced plasma BDNF
      elevations would be associated with improved indices of insulin resistance, as
      well as substrate utilization [carbohydrate oxidation (CHOoxi) and fat oxidation
      (FAToxi)]. Twenty-two healthy, untrained subjects [11 obese (four men and seven
      women; age = 22.91 +/- 4.44 years; body mass index = 35.72 +/- 4.17 kg/m(2)) and
      11 normal-weight (five men and six women; age = 23.27 +/- 2.24 years; body mass
      index = 21.89 +/- 1.63 kg/m(2))] performed 30 min of continuous submaximal
      aerobic exercise at 75% maximal oxygen consumption. Our analyses showed that the
      BDNF response to acute aerobic exercise was similar in obese and normal-weight
      subjects across time (time: P = 0.015; group: P = not significant) and was not
      associated with indices of IR. Although no differences in the rates of CHOoxi and
      FAToxi were found between both groups, total relative energy expenditure was
      significantly lower in obese subjects compared to normal-weight subjects (3.53 +/
      0.25 versus 5.59 +/- 0.85; P < 0.001). These findings suggest that acute
      exercise-elicited BDNF elevation may not be sufficient to modulate indices of IR
      or the utilization of either carbohydrates or fats in obese individuals.

PMID- 25771936
TI  - Functional outcome in major psychiatric disorders and associated clinical and
      psychosocial variables: A potential cross-diagnostic phenotype for further
      genetic investigations?
AB  - OBJECTIVES: Functional outcome has recently become of interest for cross
      diagnostic subphenotype approaches in psychiatric genetics. Therefore, it is
      crucial to know about clinical, demographic and psychosocial variables that
      correlate with long-term functioning. Unfortunately, there is a lack of studies
      that directly compare the importance of correlates for functional outcome between
      different disorders. METHODS: Applying regression models to samples of patients
      with schizophrenia (SZ, n = 238), bipolar disorder (BD, n = 533) and major
      depressive disorder (MDD, n = 398), we compared the magnitude of association of
      potential correlates with functional outcome, measured by the Global Assessment
      of Functioning (GAF) score. RESULTS: Shared correlates for worse functional
      outcome were poor premorbid functioning, insidious illness onset and poor
      premorbid work or social adjustment in all three disorders, and negative
      symptomatology in SZ and BD. Disorder-specific correlates for SZ were longer
      duration of illness, lower functioning during episodes and being life-time
      single, for BD substance abuse and suicidality, and for MDD premorbid
      unemployment and having a premorbid personality disorder. CONCLUSIONS: We found
      different patterns of correlates for long-term functioning in SZ, BD and MDD.
      Knowledge of these patterns may improve the quality of genetic investigations
      focussing on functional outcome.

PMID- 25771937
TI  - Do obsessive-compulsive disorder and Tourette syndrome share a common
      susceptibility gene? An association study of the BDNF Val66Met polymorphism in
      the Chinese Han population.
AB  - OBJECTIVES: We explored the association between the BDNF Val66Met polymorphism
      and susceptibility to both obsessive-compulsive disorder (OCD) and Tourette
      syndrome (TS) in the Chinese Han population. METHODS: Genotyping for the BDNF
      Val66Met polymorphism was performed in 321 OCD patients and 426 healthy control
      subjects and case-control association study data were analysed. Additionally, we
      evaluated the genetic contribution of this variant in 331 TS patients (including
      267 TS trios) and 519 controls using the transmission disequilibrium test (TDT)
      and case-control study. RESULTS: A statistically significant difference was found
      in the genetic contribution of the BDNF Val66Met polymorphism between both the
      OCD (chi(2) = 7.50, P = 0.023 by genotype; chi(2) = 6.67, P = 0.01 by allele) and
      TS (chi(2) = 6.76, P = 0.03 by genotype; chi(2) = 4.27, P = 0.04 by allele), and
      control groups. TDT and GHRR analysis for TS trios also showed a significant
      transform disequilibrium of this polymorphism (TDT: chi(2) = 3.96, P = 0.05;
      HHRR: chi(2) = 4.33 P = 0.04; GHRR: chi(2) = 5.74, P = 0.02; chi(2) = 0.98, P =
      0.37). There was also a significant gender trend between patients and controls in
      female cases for OCD and in male cases for TS. CONCLUSIONS: Our study supports
      the involvement of the BDNF Val66Met polymorphism as a common genetic
      susceptibility for OCD and TS in the Chinese Han population, showing specific
      gender trends.

PMID- 25771938
TI  - Presence of herpesvirus DNA in cerebrospinal fluid of patients with tick-borne
      encephalitis and enteroviral meningoencephalitis.
AB  - Reactivation of HHVs in the CNS due to inflammation has not been well described
      yet. The primary aim of this study was to investigate the frequency of HHV DNA
      detection in the cerebrospinal fluid (CSF) of immunocompetent patients with
      meningoencephalitis of other than HHV origin. The secondary aim of this study was
      to evaluate the impact of herpesvirus co-infection on the clinical course and
      patient outcome. Ninety-six patients with clinically and laboratory proven tick
      borne encephalitis (TBE) and 77 patients with a confirmed diagnosis of
      enteroviral meningitis (EVM), along with a control group of 107 patients without
      evidence of inflammation in the CSF were retrospectively tested by nested PCR for
      the presence of DNA of the neurotropic herpesviruses HSV1, HSV2, VZV, and HHV6 in
      the CSF. The clinical course, laboratory tests, antiviral treatment, and
      neurological complications in a 6-month follow-up were compared between the
      groups positive or negative for HHV DNA in the CSF. HHV DNA was found in the CSF
      of 12 (6.9%) patients (6.3% and 7.8% in the TBE and EVM groups, respectively) and
      in 1 (0.9%) control patient. None of the patients had recent blisters or rash.
      The clinical course was comparably mild in all patients. No permanent
      neurological sequelae were observed. Only the CSF total protein level was
      significantly higher in HHV DNA-positive than in HHV-negative patients.

PMID- 25771939
TI  - Aortic Dissection and Sudden Unexpected Deaths: A Retrospective Study of 31
      Forensic Autopsy Cases.
AB  - Acute aortic dissection (AAD) is the most common cause of sudden unexpected death
      related to aortic diseases. A retrospective study of 31 sudden unexpected deaths
      caused by AAD was conducted at Xi'an Jiaotong University Forensic Center from
      2001 to 2012. We summarized the forensic characteristics of AAD and assessed the
      clinically diagnostic accuracy of AAD. The characteristics of sudden unexpected
      death due to AAD were male predominant (male: female=6.7:1), relatively young
      with the mean age of 44, and predominance of type A dissection (77.4%). Cardiac
      tamponade was the most frequent cause of sudden death (87.1%). Of the 31 cases,
      26 (83.9%) patients were not recognized clinically and were misdiagnosed with
      acute myocardial infarction, coronary artery disease, cholecystitis, acute
      gastroenteritis, renal/urinary lithiasis, or acute pancreatitis. In summary, AAD
      can be difficult to recognize, diagnosis is therefore sometimes delayed or
      missed. The medicolegal death investigation can help physicians have a better
      understanding of AAD.

PMID- 25771940
TI  - Sustainability and public health nutrition at school: assessing the integration
      of healthy and environmentally sustainable food initiatives in Vancouver schools.
AB  - OBJECTIVE: To describe the development and application of the School Food
      Environment Assessment Tools and a novel scoring system to assess the integration
      of healthy and environmentally sustainable food initiatives in elementary and
      secondary schools. DESIGN: The cross-sectional study included direct observations
      of physical food environments and interviews with key school personnel regarding
      food-related programmes and policies. A five-point scoring system was then
      developed to assess actions across six domains: (i) food gardens; (ii) composting
      systems; (iii) food preparation activities; (iv) food-related teaching and
      learning activities; and availability of (v) healthy food; and (vi)
      environmentally sustainable food. SETTING: Vancouver, Canada. SUBJECTS: A
      purposive sample of public schools (n 33) from all six sectors of the Vancouver
      Board of Education. RESULTS: Schools scored highest in the areas of food garden
      and compost system development and use. Regular integration of food-related
      teaching and learning activities and hands-on food preparation experiences were
      also commonly reported. Most schools demonstrated rudimentary efforts to make
      healthy and environmentally sustainable food choices available, but in general
      scored lowest on these two domains. Moreover, no schools reported widespread
      initiatives fully supporting availability or integration of healthy or
      environmentally sustainable foods across campus. CONCLUSIONS: More work is needed
      in all areas to fully integrate programmes and policies that support healthy,
      environmentally sustainable food systems in Vancouver schools. The assessment
      tools and proposed indicators offer a practical approach for researchers, policy
      makers and school stakeholders to assess school food system environments,
      identify priority areas for intervention and track relevant changes over time.

PMID- 25771941
TI  - Marginal Adaptation Evaluation of Biodentine and MTA Plus in "Open Sandwich"
      Class II Restorations.
AB  - PURPOSES: This study aimed at evaluation of two different commercially available
      calcium silicate materials (Biodentine and mineral trioxide aggregate [MTA] Plus)
      used as dentin substitute. MATERIALS AND METHODS: Sixty Class II cavities were
      prepared in extracted mandibular third molars, with margins extending 1 mm below
      the cementum-enamel junction. The samples were divided into three groups on the
      basis of dentin substitute used: resin modified glass ionomer cement, Biodentine,
      and MTA Plus. Cavities were restored with composite resins in an "open sandwich"
      technique. The samples were subjected to alternate aging in phosphate buffered
      saline and cyclic loading. Marginal adaptation was evaluated in terms of
      "continuous margin" at the gingival margin, using a low vacuum scanning electron
      microscope. Statistical analysis was done with two-way analysis of variance with
      Holm-Sidak's correction for multiple comparisons. RESULTS: The glass ionomer
      group and Biodentine group presented an overall 83% and 91% of continuous
      margins, with no difference between them. MTA Plus showed least values of
      continuous margins. Granular deposits were seen over the surface of Biodentine
      and MTA Plus. CONCLUSIONS: Biodentine and resin-modified glass ionomer cement,
      when used as a dentin substitute under composite restorations in open sandwich
      technique, gave satisfactory marginal adaptation values. CLINICAL SIGNIFICANCE:
      Contemporary calcium silicate materials can be used as dentin substitute
      materials in "open sandwich" Class II restorations. This study evaluates the
      marginal adaptation of Biodentine, MTA Plus, and resin modified glass ionomer
      cement used as dentin substitutes and reports better adaptation obtained with
      Biodentine and glass ionomer cement.

PMID- 25771942
TI  - Plant herbivory responses through changes in leaf quality have no effect on
      subsequent leaf-litter decomposition in a neotropical rain forest tree community.
AB  - It is commonly accepted that plant responses to foliar herbivory (e.g. plant
      defenses) can influence subsequent leaf-litter decomposability in soil. While
      several studies have assessed the herbivory-decomposability relationship among
      different plant species, experimental tests at the intra-specific level are rare,
      although critical for a mechanistic understanding of how herbivores affect
      decomposition and its consequences at the ecosystem scale. Using 17 tree species
      from the Yasuni National Park, Ecuadorian Amazonia, and applying three different
      herbivore damage treatments, we experimentally tested whether the plant intra
      specific responses to herbivory, through changes in leaf quality, affect
      subsequent leaf-litter decomposition in soil. We found no effects of herbivore
      damage on the subsequent decomposition of leaf litter within any of the species
      tested. Our results suggest that leaf traits affecting herbivory are different
      from those influencing decomposition. Herbivore damage showed much higher intra
      specific than inter-specific variability, while we observed the opposite for
      decomposition. Our findings support the idea that interactions between consumers
      and their resources are controlled by different factors for the green and the
      brown food-webs in tropical forests, where herbivory may not necessarily generate
      any direct positive or negative feedbacks for nutrient cycling. 

PMID- 25771943
TI  - Prophylaxis for Pneumocystis jiroveci pneumonia: is it a necessity in pulmonary
      patients on high-dose, chronic corticosteroid therapy without AIDS?
AB  - The benefit of prophylaxis for Pneumocystis jirovecii pneumonia (PJP) is well
      documented in immunocompromised patients, particularly those with HIV and/or
      AIDS; therefore, guidelines dictate this as standard of care. However, there is a
      paucity of literature regarding those without HIV and/or AIDS who are potentially
      predisposed to PJP, including patients with sarcoidosis, cryptogenic organizing
      pneumonia, interstitial lung disease, asthma and chronic obstructive pulmonary
      disease, who may require high dose of prolonged corticosteroids for disease
      maintenance or to prevent relapses. In this review, the authors examine the
      available literature regarding prophylaxis in these groups, elaborate on the
      pathogenesis of PJP, when to suspect PJP in these patients, as well as explore
      current recommendations that guide clinical practice regarding implementation of
      PJP prophylaxis, namely with trimethoprim/sulfamethoxazole being the preferred
      agent. In summary, the role of PJP prophylaxis in non-HIV patients on chronic
      steroids remains controversial. The authors present a review of the literature to
      provide better guidance to the clinician regarding the need to initiate PJP
      prophylaxis in this patient population. 

PMID- 25771944
TI  - Dietary protein intake affects expression of genes for lipid metabolism in
      porcine skeletal muscle in a genotype-dependent manner.
AB  - Skeletal muscle is a major site for the oxidation of fatty acids (FA) in mammals,
      including humans. Using a swine model, we tested the hypothesis that dietary
      protein intake regulates the expression of key genes for lipid metabolism in
      skeletal muscle. A total of ninety-six barrows (forty-eight pure-bred Bama mini
      pigs (fatty genotype) and forty-eight Landrace pigs (lean genotype)) were fed
      from 5 weeks of age to market weight. Pigs of fatty or lean genotype were
      randomly assigned to one of two dietary treatments (low- or adequate-protein
      diet), with twenty-four individually fed pigs per treatment. Our data showed that
      dietary protein levels affected the expression of genes involved in the anabolism
      and catabolism of lipids in the longissimus dorsi and biceps femoris muscles in a
      genotype-dependent manner. Specifically, Bama mini-pigs had more intramuscular
      fat, SFA and MUFA, as well as elevated mRNA expression levels of lipogenic genes,
      compared with Landrace pigs. In contrast, Bama mini-pigs had lower mRNA
      expression levels of lipolytic genes than Landrace pigs fed an adequate-protein
      diet in the growing phase. These data are consistent with higher white-fat
      deposition in Bama mini-pigs than in Landrace pigs. In conclusion, adequate
      provision of dietary protein (amino acids) plays an important role in regulating
      the expression of key lipogenic genes, and the growth of white adipose tissue, in
      a genotype- and tissue-specific manner. These findings have important
      implications for developing novel dietary strategies in pig production. 

PMID- 25771945
TI  - Feed the brain: insights into the study of neurovascular coupling.
AB  - The microcirculation is tightly regulated by a diverse range of mechanisms which
      share the common goal of matching blood flow delivery with tissue metabolic
      demand. Despite in-depth examination of tissues like skeletal muscle, brain
      microcirculation has remained largely unexplored due to methodological
      limitations. Recent, technological advances have, however, started to grant
      greater access to this vital microcirculatory bed. This overview is part of a
      Special Topics Issue centered on the methodology, theory, and mechanistic basis
      of neurovascular coupling. Solicited manuscripts have been purposely written in
      an opinionated manner to provoke thought and to illuminate new emerging areas of
      investigation. 

PMID- 25771946
TI  - Marmoset neuroscience.

PMID- 25771947
TI  - Cutaneous dirt-adherent disease on the base of keloid.

PMID- 25771948
TI  - The atherosclerosis burden score (ABS): a convenient ultrasound-based score of
      peripheral atherosclerosis for coronary artery disease prediction.
AB  - Ultrasonographic detection of subclinical atherosclerosis improves cardiovascular
      risk stratification, but uncertainty persists about the most discriminative
      method to apply. In this study, we found that the "atherosclerosis burden score
      (ABS)", a novel straightforward ultrasonographic score that sums the number of
      carotid and femoral arterial bifurcations with plaques, significantly
      outperformed common carotid intima-media thickness, carotid mean/maximal
      thickness, and carotid/femoral plaque scores for the detection of coronary artery
      disease (CAD) (receiver operating characteristic (ROC) curve area under the curve
      (AUC) = 0.79; P = 0.027 to <0.001 with the other five US endpoints) in 203
      patients undergoing coronary angiography. ABS was also more correlated with CAD
      extension (R = 0.55; P < 0.001). Furthermore, in a second group of 1128 patients
      without cardiovascular disease, ABS was weakly correlated with the European
      Society of Cardiology chart risk categories (R(2) = 0.21), indicating that ABS
      provided information beyond usual cardiovascular risk factor-based risk
      stratification. Pending prospective studies on hard cardiovascular endpoints, ABS
      appears as a promising tool in primary prevention.

PMID- 25771950
TI  - The forthcoming inexorable decline of cutaneous melanoma mortality in light
      skinned populations.
AB  - BACKGROUND: Reasons underlying time changes in cutaneous melanoma mortality in
      light-skinned populations are not well understood. An analysis of long-term time
      trends in melanoma mortality was carried out after regrouping countries in
      homogeneous regions. METHODS: Using the World Health Organisation (WHO) mortality
      database, age-period-cohort models were fitted for seven regions where the
      majority of population is light-skinned. Cohort effects are denoted as changes in
      rates occurring at different times in steadily older age groups. Period effects
      are denoted as changes in rates occurring simultaneously in several age groups.
      RESULTS: Cohort effects better explained changes in melanoma mortality over time
      than period effects. Lifetime risk to die from melanoma increased in successive
      generations from 1875 until a peak year. Peak years were for subjects born in
      1936-1940 in Oceania, 1937-1943 in North America, 1941-1942 in Northern Europe,
      1945-1953 in the United Kingdom (UK) and Ireland, 1948 in Western Europe and 1957
      in Central Europe. After peak years, lifetime risk of melanoma death gradually
      decreased in successive generations and risks of subjects born in 1990-1995 were
      back to risk levels observed for subjects born before 1900-1905. In Southern
      Europe, birth years with highest lifetime risk of melanoma death have not yet
      been attained. As time passes, melanoma deaths will steadily rarefy in younger
      age groups and concentrate in older age groups, for ultimately fade away after
      2040-2050. CONCLUSION: Independently from screening or treatment, over next
      decades, death from melanoma is likely to become an increasingly rare event. The
      temporary epidemic of fatal melanoma was most probably due to excessive UV
      exposure of children that prevailed in 1900-1960, and mortality decreases would
      be due to progressive reductions in UV-exposure of children over the last
      decades.

PMID- 25771949
TI  - BNP and Heart Failure: Preclinical and Clinical Trial Data.
AB  - The B-type natriuretic peptide (BNP), a member of the family of vasoactive
      peptides, has emerged as an important diagnostic, prognostic, and therapeutic
      tool in patients with heart failure (HF). The rapid incorporation into clinical
      practice of bioassays to BNP concentrations and pharmacological agents that
      augment the biological actions of this peptide such as nesiritide or
      vasopeptidase inhibitors has shown the potential for translational research to
      improve patient care. Despite the indirect evidence in support of a potential
      benefit from raising BNP, accumulating evidence suggests that simply increasing
      the amount of circulating BNP does not necessarily confer cardiovascular benefits
      in patient with HF. Moreover, in experimental HF, the response to treatments
      targeting specific natriuretic peptide receptors (NPRs) signaling seems to be
      attenuated. A better understanding of the NPRs signaling in HF would be
      clinically relevant and thus required, in order to devise strategies to develop
      novel agents and technologies that directly target this signaling pathway. 

PMID- 25771951
TI  - Erythema multiforme-type drug eruption with prominent keratinocyte necrosis
      induced by long-term administration of telmisartan.

PMID- 25771953
TI  - Two-pore-domain potassium channels: regulators of many cellular functions.

PMID- 25771952
TI  - Extracellular sodium and potassium levels modulate cardiac conduction in mice
      heterozygous null for the Connexin43 gene.
AB  - Several studies have disagreed on measurements of cardiac conduction velocity
      (CV) in mice with a heterozygous knockout of the connexin gene Gja1--a mutation
      that reduces the gap junction (GJ) protein, Connexin43 (Cx43), by 50 %. We noted
      that perfusate ionic composition varied between studies and hypothesized that
      extracellular ionic concentration modulates CV dependence on GJs. CV was measured
      by optically mapping wild-type (WT) and heterozygous null (HZ) hearts serially
      perfused with solutions previously associated with no change (Solution 1) or CV
      slowing (Solution 2). In WT hearts, CV was similar for Solutions 1 and 2.
      However, consistent with the hypothesis, Solution 2 in HZ hearts slowed
      transverse CV (CVT) relative to Solution 1. Previously, we showed CV slowing in a
      manner consistent with ephaptic conduction correlated with increased perinexal
      inter-membrane width (W P) at GJ edges. Thus, W P was measured following
      perfusion with systematically adjusted [Na(+)]o and [K(+)]o in Solutions 1 and 2.
      A wider W P was associated with reduced CVT in WT and HZ hearts, with the
      greatest effect in HZ hearts. Increasing [Na(+)]o increased CVT only in HZ
      hearts. Increasing [K(+)]o slowed CVT in both WT and HZ hearts with large W P but
      only in HZ hearts with narrow W P. CONCLUSION: When perinexi are wide, decreasing
      excitability by modulating [Na(+)]o and [K(+)]o increases CV sensitivity to
      reduced Cx43. By contrast, CV is less sensitive to Cx43 and ion composition when
      perinexi are narrow. These results are consistent with cardiac conduction
      dependence on both GJ and non-GJ (ephaptic) mechanisms.

PMID- 25771955
TI  - Arrest and Calcification Repair of internal root resorption with a novel
      treatment approach: Report of two cases.
AB  - AIM: We report a novel treatment option for teeth with internal root resorption
      (IRR) in which the lesion had perforated to the PDL and was located in the
      coronal aspect of the root. Arrest and calcification of IRR can be achieved by
      local application of calcium hydroxide without further intracanal
      instrumentation. CASE REPORT: Two cases of severe IRR without periapical
      inflammation were treated with a novel technique: The vital pulp including the
      granuloma was left in place and subjected to long-term disinfection with
      application of calcium hydroxide in the coronal aspect of the IRR. In both cases,
      the radiolucent areas were reduced and showed progressive calcification. Solid
      barriers were found in the coronal layers of the IRRs, and mineral trioxide
      aggregate (MTA) was placed as definitive fillings. No apical periodontitis was
      seen during the follow-up period of 6 years. The root canals appeared to
      gradually be narrowed. The results were similar to those obtained after
      successful cervical pulpotomy. Thus, the biological outcome was improved in
      comparison with pulp extirpation and conventional root canal treatment. KEY
      LEARNING POINTS OF THIS ARTICLE: A treatment option for internal root resorption
      without periapical inflammation.

PMID- 25771954
TI  - Functional assessment of three Rem residues identified as critical for
      interactions with Ca(2+) channel beta subunits.
AB  - Members of the Rem, Rem2, Rad, Gem/Kir (RGK) family of small GTP-binding proteins
      inhibit high-voltage-activated (HVA) Ca(2+) channels through interactions with
      both the principal alpha1 and the auxiliary beta subunits of the channel complex.
      Three highly conserved residues of Rem (R200, L227, and H229) have been shown in
      vitro to be critical for interactions with beta subunits. However, the functional
      significance of these residues is not known. To investigate the contributions of
      R200, L227, and H229 to beta subunit-mediated RGK protein-dependent inhibition of
      HVA channels, we introduced alanine substitutions into all three positions of
      Venus fluorescent protein-tagged Rem (V-Rem AAA) and made three other V-Rem
      constructs with an alanine introduced at only one position (V-Rem R200A, V-Rem
      L227A, and V-Rem H229A). Confocal imaging and immunoblotting demonstrated that
      each Venus-Rem mutant construct had comparable expression levels to Venus-wild
      type Rem when heterologously expressed in tsA201 cells. In electrophysiological
      experiments, V-Rem AAA failed to inhibit N-type Ca(2+) currents in tsA201 cells
      coexpressing CaV2.2 alpha1B, beta3, and alpha2delta-1 channel subunits. The V-Rem
      L227A single mutant also failed to reduce N-type currents conducted by
      coexpressed CaV2.2 channels, a finding consistent with the previous observation
      that a leucine at position 227 is critical for Rem-beta interactions. Rem
      dependent inhibition of CaV2.2 channels was impaired to a much lesser extent by
      the R200A substitution. In contrast to the earlier work demonstrating that Rem
      H229A was unable to interact with beta3 subunits in vitro, V-Rem H229A produced
      nearly complete inhibition of CaV2.2-mediated currents. 

PMID- 25771956
TI  - The picture of happiness in Alzheimer's disease: living a life congruent with
      personal values.
AB  - It is generally understood that happiness is an important goal of dementia care,
      though evaluation has been challenging. Concerns about cognitive and
      communicative limitations have led to the use of proxy reports to assess positive
      affect. However, proxy reports have been shown to differ from appraisals obtained
      by the person with Alzheimer's disease (AD). This article reports on a
      qualitative study of happiness in a sample of 12 persons with mild to moderate AD
      using photo-elicitation and individual interviews for data collection. Results
      demonstrate people with mild to moderate AD can provide meaningful evaluations of
      happiness, and that lifelong values continue to be important in the presence of
      AD. This study suggests photographs may offer a novel approach to obtain a
      contextualized understanding of happiness and other values in this population
      which may lead to the development of person centered interventions aimed to
      improve the individual's quality of life. 

PMID- 25771957
TI  - Acceptability of wristband activity trackers among community dwelling older
      adults.
AB  - Wristband activity trackers have become widely used among young adults. However,
      few studies have explored their use for monitoring and improving health outcomes
      among older adults. The purpose of this study was to evaluate the feasibility and
      utility of activity tracker use among older adults for monitoring activity,
      improving self-efficacy, and health outcomes. A 12-week pilot study was conducted
      to evaluate the feasibility and utility of mobile wristband activity trackers.
      The sample (N = 34) was 65% women 73.5 +/- 9.4 years of age who had a high school
      diploma or GED (38%) and reported an income <=$35,000 (58%). Participants
      completing the study (95%) experienced a decrease in waist circumference (p >
      0.009), however no change in self-efficacy. Participants found activity trackers
      easy to use which contributed to minimal study withdrawals. It was concluded that
      activity trackers could be useful for monitoring and promoting physical activity
      and improving older adults' health. 

PMID- 25771959
TI  - Evolution, kinetics, energetics, and environmental factors of graphene
      degradation on silicon dioxide.
AB  - Recent studies have qualitatively shown that the oxidative stability of monolayer
      graphene integrated on oxides is relatively poor. Here, the evolution, kinetics,
      and energetics of this degradation are quantified. Specifically, the
      deterioration of graphene on SiO2 is studied in grain interiors and at grain
      boundaries in ambient air, dry air and nitrogen between 473 and 673 K, using
      spatially and temporally resolved in situ Raman spectroscopy in addition to
      electron microscopy and charge transport measurements. The grain interiors of
      chemical vapor deposition (CVD) grown graphene monolayers oxidize with an
      activation energy of 0.63 +/- 0.05 eV in ambient air (15,000 ppm H2O). This
      energy increases to 1.85 +/- 0.17 eV in dry air, whereas degradation is
      immeasurable in nitrogen and for multilayers even in ambient air. Gasification at
      grain boundaries in a CVD monolayer proceeds at a rate of (1.08 +/- 0.02) * 10(
      1) nm s(-1) at 673 K with an activation energy E(A) = 1.14 +/- 0.10 eV in ambient
      air. The more facile degradation of the monolayer grain interiors in ambient air
      indicates the role of the substrate in decreasing the stability against
      oxidation. The electrical transport mobility decays with an activation rate
      similar to that of grain interiors. These results can be used to quantitatively
      predict graphene oxidation and gasification on SiO2 in different environments and
      temperatures.

PMID- 25771958
TI  - Body mass index as discriminator of the lean mass deficit and excess body fat in
      institutionalized elderly people.
AB  - The objective of this study was to identify the discriminating criterion for body
      mass index (BMI) in the prediction of low fat free mass and high body fat
      percentage according to sex among older people. Observational analytical study
      with cross-sectional design was used for this study. All institutionalized older
      people from the city of Uberaba (Minas Gerais, Brazil) who fit within the
      inclusion and exclusion criteria were approached. Sixty-five institutionalized
      older people were evaluated after signing a Free and Informed Consent Form.
      Descriptive and inferential statistical procedures were employed for the
      analysis, using Student's t-test and multiple linear regression. Receiver
      Operating Characteristic (ROC) curves were constructed to determine the BMI
      (kg/m(2)) cut-off points. The study complied with all the ethical norms for
      research involving human beings. In comparing the anthropometric measurements
      obtained via bioimpedance, elder male had higher mean height and body water
      volume than females. However, women had higher mean triceps skinfold and fat free
      mass than men. The BMI cut-off points, as discriminators of low fat free mass
      percentage and high body fat percentage in women, were <=22.4 kg/m(2) and >26.6
      kg/m(2), respectively; while for men they were <=19.2 kg/m(2) and >23.8 kg/m(2).
      The results of this study indicate the need for multicenter studies aimed at
      suggesting BMI cut-off points for institutionalized older people, taking into
      account specific sex characteristics. 

PMID- 25771960
TI  - Age matters: the effects of volatile organic compounds emitted by Trichoderma
      atroviride on plant growth.
AB  - Studying the effects of microbial volatile organic compounds (VOCs) on plant
      growth is challenging because the production of volatiles depends on many
      environmental factors. Adding to this complexity, the method of volatile exposure
      itself can lead to different responses in plants and may account for some of the
      contrasting results. In this work, we present an improved experimental design, a
      plate-within-a-plate method, to study the effects of VOCs produced by filamentous
      fungi. We demonstrate that the plant growth response to VOCs is dependent on the
      age of the plant and fungal cultures. Plants exposed to volatiles emitted by 5
      day-old Trichoderma atroviride for 14 days exhibited inhibition, while plants
      exposed to other exposure conditions had growth promotion or no significant
      change. Using GC-MS, we compared fungal volatile emission of 5-day-old and 14-day
      old T. atroviride. As the fungi aged, a few compounds were no longer detected,
      but 24 new compounds were discovered.

PMID- 25771962
TI  - Withdrawn: MicroRNAs as potential regulators of docosahexaenoic acid benefits in
      Alzheimer's disease.
AB  - Withdrawal: We regret that it has become necessary to withdraw this article
      published online ahead of print on the 14th March 2015 in Nutritional
      Neuroscience. At the time of publication, the author of this paper was no longer
      a registered student at the the University of Auckland and the paper was
      published without the University's permission. The Editor and publisher acted in
      good faith on the basis of the information available at the time of acceptance
      and remain committed to the highest ethical and scientific standards in the peer
      review and publication of submissions.

PMID- 25771961
TI  - Study of pharmacokinetics of an in situ forming gel system for controlled
      delivery of florfenicol in pigs.
AB  - To reduce florfenicol (FFC) administration frequency in veterinary use, the drug
      was currently developed into in situ forming gel. Twelve pigs were randomly
      divided into two groups (six pigs per group). A single i.m. dose of 40 mg/kg body
      weight (b.w.) was given to pigs, group one was given FFC in situ forming gel, and
      group two was given FFC conventional injection. High-performance liquid
      chromatography (HPLC) was used to determine FFC plasma concentrations. There were
      significant differences (P < 0.01) between FFC in situ forming gel and
      conventional injection, in pharmacokinetic parameters MRT (mean retention time)
      (57.79 +/- 2.88) h versus (15.94 +/- 1.29) h, AUC (area under the concentration
      time curve) (421.54 +/- 8.97) MUg.h/mL versus (168.16 +/- 4.59) MUg.h/mL, tmax
      (time of occurrence of cmax ) (9.00 +/- 2.68) h versus (4.33 +/- 0.82) h, cmax
      (maximum plasma concentration) (6.87 +/- 0.66) MUg/mL versus (12.01 +/- 0.66)
      MUg/mL, t1/2lambdaz (terminal elimination half-life) (38.04 +/- 2.20) h versus
      (9.15 +/- 2.71) h. The results demonstrated that the in situ forming gel system
      could shorten dosing interval of FFC and thus achieved less frequent
      administration during long-term treatment. 

PMID- 25771963
TI  - Droplet-based electro-coalescence for probing threshold disjoining pressure.
AB  - In this work, we investigate the coalescence of emulsion droplets in a controlled
      electric field. Two contacting droplets stabilized by surfactants can be forced
      to coalesce into a combined one when the applied voltage is above a critical
      value. The critical voltages change with the types, concentrations of surfactants
      and temperature. By exploring the drainage of a thin oil film trapped between
      emulsions, we interpret that the coalescence occurs as the electric compression
      overcomes the disjoining pressure barrier and squeezes the film to a critical
      thickness. Based on this, we have devised an approach to probe the threshold
      disjoining pressure which can help predict the emulsion stability and surfactant
      efficacy quantitatively. We have confirmed the validity of our approach for
      measuring the threshold disjoining pressure by comparing the result with other
      proven tests that involve centrifugation and thermal heating. Our approach is
      simple, reliable and robust in predicting emulsion stability and will facilitate
      the design of emulsion-based formulations by accelerating the testing of emulsion
      stability. 

PMID- 25771964
TI  - Pauses enhance chunk recognition in song element strings by zebra finches.
AB  - When learning a language, it is crucial to know which syllables of a continuous
      sound string belong together as words. Human infants achieve this by attending to
      pauses between words or to the co-occurrence of syllables. It is not only humans
      that can segment a continuous string. Songbirds learning their song tend to copy
      'chunks' from one or more tutors' songs and combine these into their own song. In
      the tutor songs, these chunks are often separated by pauses and a high co
      occurrence of elements, suggesting that these features affect chunking and song
      learning. We examined experimentally whether the presence of pauses and element
      co-occurrence affect the ability of adult zebra finches to discriminate strings
      of song elements. Using a go/no-go design, two groups of birds were trained to
      discriminate between two strings. In one group (Pause-group), pauses were
      inserted between co-occurring element triplets in the strings, and in the other
      group (No-pause group), both strings were continuous. After making a correct
      discrimination, an individual proceeded to a reversal training using string
      segments. Segments were element triplets consistent in co-occurrence, triplets
      that were partly consistent in composition and triplets consisting of elements
      that did not co-occur in the strings. The Pause-group was faster in
      discriminating between the two strings. This group also responded differently to
      consistent triplets in the reversal training, compared to inconsistent triplets.
      The No-pause group did not differentiate among the triplet types. These results
      indicate that pauses in strings of song elements aid song discrimination and
      memorization of co-occurring element groups. 

PMID- 25771965
TI  - The order of ostensive and referential signals affects dogs' responsiveness when
      interacting with a human.
AB  - Ostensive signals preceding referential cues are crucial in communication-based
      human knowledge acquisition processes. Since dogs are sensitive to both human
      ostensive and referential signals, here we investigate whether they also take
      into account the order of these signals and, in an object-choice task, respond to
      human pointing more readily when it is preceded by an ostensive cue indicating
      communicative intent. Adult pet dogs (n = 75) of different breeds were presented
      with different sequences of a three-step human action. In the relevant sequence
      (RS) condition, subjects were presented with an ostensive attention getter
      (verbal addressing and eye contact), followed by referential pointing at one of
      two identical targets and then a non-ostensive attention getter (clapping of
      hands). In the irrelevant sequence (IS) condition, the order of attention getters
      was swapped. We found that dogs chose the target indicated by pointing more
      frequently in the RS as compared to the IS condition. While dogs selected
      randomly between the target locations in the IS condition, they performed
      significantly better than chance in the RS condition. Based on a further control
      experiment (n = 22), it seems that this effect is not driven by the aversive or
      irrelevant nature of the non-ostensive cue. This suggests that dogs are sensitive
      to the order of signal sequences, and the exploitation of human referential
      pointing depends on the behaviour pattern in which the informing cue is embedded.

PMID- 25771966
TI  - Risk should be objectively defined: reply to Zentall and Smith.
AB  - Zentall and Smith (2014) have published a comment on Pele and Sueur (Anim Cogn
      16:543-556, 2013) in which they raise two issues, one about the definition of
      risk and a second concerning the optimality of decisions. When making a choice,
      subjects are faced not only with several possible alternatives but also with the
      risk of opting for an unsuitable choice which depends on several variables
      (context, internal state, knowledge and perception). Although it is true that
      animals might learn about their environment and adapt their decisions to the
      context and to their experience, strong constraints make some behavioural traits
      stable over individual lifetime and even generations. We therefore consider that
      experience has limited impact on the variability of temporal discounting. These
      behavioural traits make the difference between perceived and actual risk. If the
      perceived risk strongly differs from the actual risk, a decision should be
      considered as suboptimal. If we want to lead individual and collective cognition
      to a common decision science, it is crucial to use the same definitions for terms
      implied in decision-making. 

PMID- 25771967
TI  - Desire for a youthful look is associated with daily sunscreen use: results of a
      questionnaire-based study.

PMID- 25771968
TI  - Direct fluorination of styrenes.
AB  - We have developed a practical method to synthesize fluorostyrene compounds. A
      mild and regioselective mono-fluorination reaction occurred smoothly for various
      di- and trisubstituted styrenes in the presence of RuCl3 and N
      fluorobenzenesulfonimide (NFSI). A tandem alkyne hydroarylation-olefin
      fluorination reaction was also developed using an Au catalyst. 

PMID- 25771969
TI  - Preferential recognition of isocitrate dehydrogenase by a rabbit monoclonal
      antibody (ab124797) against the C-terminal peptide of RANKL.
AB  - A rabbit monoclonal antibody (Abcam ab124797), with high affinity for a synthetic
      peptide corresponding to the C-terminal region of the receptor activator of
      nuclear factor (NF)-kappaB ligand (RANKL), specifically recognizes a 37 kDa
      protein by immunoblotting, in good agreement with the molecular mass of RANKL.
      However, our mass spectroscopy analysis revealed that the protein recognized by
      the antibody is the alpha-subunit of NAD(+)-dependent isocitrate dehydrogenase
      (ICDH), a key Krebs cycle enzyme in mitochondria. Consistently,
      immunocytochemical staining with the antibody revealed a network organization
      characteristic of mitochondria, which overlapped with staining by MitoTracker and
      was lost after the siRNA-mediated downregulation of ICDH. The C-terminal peptide
      of ICDH contains similar chemical characteristics to that of the RANKL peptide
      and interacts with the antibody, although the affinity is a hundred times weaker.
      The present study provides an example of the preferential recognition of a
      surrogate protein by a rabbit monoclonal antibody.

PMID- 25771970
TI  - Sensitive recovery of recombinant antibody clones after their in silico
      identification within NGS datasets.
AB  - Recently the analytical power of the latest high throughput next generation DNA
      sequencing platforms has been used to analyse phage that have been selected from
      the panning of large combinatorial libraries displaying either peptide or
      antibody ligands. This process, commonly referred to as next generation phage
      display (NGPD), allows the researcher to determine the identity of specific phage
      that are being enriched against an antigen target by analysis of the DNA sequence
      encoding the displayed ligand. This method bypasses several steps in conventional
      phage panning that include laborious colony picking and functional ligand
      screening. A downside of this approach is that the only output from such
      experiments is the DNA sequence information of such enriched phage particles. In
      the case of peptides, the peptide sequence can be synthesised directly and used
      for further screening; however this is more difficult with larger antibody
      fragments such as ScFvs. In the case of ScFvs, their coding sequence would have
      to be fully elucidated, synthesised and re-cloned before expression. We describe
      here the application of an inverse PCR-ligation methodology that enables the
      specific recovery of ScFvs of interest from enriched sub-libraries of phage
      clones. Phagemid particles are recovered using sequence information derived from
      their unique heavy chain CDR3/FR4 domains and specific clones can be recovered
      irrespective of CDR3 size and at levels of abundance that would be refractory to
      their discovery during conventional phage panning and screening. 

PMID- 25771971
TI  - Initiating intrajejunal infusion of levodopa/carbidopa intestinal gel: an
      outpatient model.

PMID- 25771972
TI  - alpha2-Adrenoceptors in the treatment of major neuropsychiatric disorders.
AB  - Presynaptic autoreceptors mediate a retrograde transfer of information by a
      negative feedback mechanism mediated by the transmitter of the neuron, and
      fulfill an autoregulatory function in neurotransmission in the peripheral and
      central nervous system (CNS). Starting with norepinephrine (NE), it was later
      reported that an autoreceptor-mediated negative feedback mechanism exists for
      other neurotransmitters, including dopamine (DA), serotonin, acetylcholine,
      histamine, GABA, and glutamate. This feedback mechanism regulates calcium
      dependent transmitter release and synthesis through terminal presynaptic
      autoreceptors, while the firing rate of the neuron is regulated through
      somatodendritic autoreceptors. 

PMID- 25771973
TI  - Identification of a novel GATA3 mutation in a deaf Taiwanese family by massively
      parallel sequencing.
AB  - Recent studies have confirmed the utility of massively parallel sequencing (MPS)
      in addressing genetically heterogeneous hereditary hearing impairment. By
      applying a MPS diagnostic panel targeting 129 known deafness genes, we identified
      a novel frameshift GATA3 mutation, c.149delT (p.Phe51LeufsX144), in a hearing
      impaired family compatible with autosomal dominant inheritance. The GATA3
      haploinsufficiency is thought to be associated with the hypoparathyroidism,
      sensorineural deafness, and renal dysplasia (HDR) syndrome. The pathogenicity of
      GATA3 c.149delT was supported by its absence in the 5400 NHLBI exomes, 1000
      Genomes, and the 100 normal hearing controls of the present study; the co
      segregation of c.149delT heterozygosity with hearing impairment in 9 affected
      members of the family; as well as the nonsense-mediated mRNA decay of the mutant
      allele in in vitro functional studies. The phenotypes in this family appeared
      relatively mild, as most affected members presented no signs of
      hypoparathyroidism or renal abnormalities, including the proband. To our
      knowledge, this is the first report of genetic diagnosis of HDR syndrome before
      the clinical diagnosis. Genetic examination for multiple deafness genes with MPS
      might be helpful in identifying certain types of syndromic hearing loss such as
      HDR syndrome, contributing to earlier diagnosis and treatment of the affected
      individuals. 

PMID- 25771974
TI  - Expression status of candidate genes in mesothelioma tissues and cell lines.
AB  - In order to broaden knowledge on the pathogenesis of malignant pleural
      mesothelioma (MPM), we reviewed studies on the MPM-transcriptome and identified
      119 deregulated genes. However, there was poor consistency among the studies.
      Thus, the expression of these genes was further investigated in the present work
      using reverse transcriptase-quantitative PCR (RT-qPCR) in 15 MPM and 20 non-MPM
      tissue samples. Fifty-nine genes showed a statistically significant deregulation
      and were further evaluated in two epithelioid MPM cell lines (compared to MET-5A,
      a non-MPM cell line). Nine genes (ACSL1, CCNO, CFB, PDGFRB, SULF1, TACC1, THBS2,
      TIMP3, XPOT) were deregulated with statistical significance in both cell lines,
      12 (ASS1, CCNB1, CDH11, COL1A1, CXADR, EIF4G1, GALNT7, ITGA4, KRT5, PTGIS, RAN,
      SOD1) in at least one cell line, whereas 7 (DSP, HEG1, MCM4, MSLN, NME2, NMU,
      TNPO2) were close but did not reach the statistical significance in any of the
      cell line. Patients whose MPM tissues expressed elevated mRNA levels of BIRC5,
      DSP, NME2, and THBS2 showed a statistically significant shorter overall survival.
      Although MPM is a poorly studied cancer, some features are starting to emerge.
      Novel cancer genes are suggested here, in particular those involved in cell-cell
      and cell-matrix interactions. 

PMID- 25771975
TI  - Compartmental stress responses correlate with cell survival in bystander effects
      induced by the DNA damage agent, bleomycin.
AB  - Physical or chemical stress applied to a cell system trigger a signal cascade
      that is transmitted to the neighboring cell population in a process known as
      bystander effect. Despite its wide occurrence in biological systems this
      phenomenon is mainly documented in cancer treatments. Thus understanding whether
      the bystander effect acts as an adaptive priming element for the neighboring
      cells or a sensitization factor is critical in designing treatment strategies.
      Here we characterize the bystander effects induced by bleomycin, a DNA-damaging
      agent, and compartmental stress responses associated with this phenomenon. Mouse
      fibroblasts were treated with increasing concentrations of bleomycin and assessed
      for DNA damage, cell death and induction of compartmental stress response
      (endoplasmic reticulum, mitochondrial and cytoplasmic stress). Preconditioned
      media were used to analyze bystander damage using the same end-points. Bleomycin
      induced bystander response was reflected primarily in increased DNA damage. This
      was dependent on the concentration of bleomycin and time of media conditioning.
      Interestingly, we found that ROS but not NO are involved in the transmission of
      the bystander effect. Consistent transcriptional down-regulation of the stress
      response factors tested (i.e. BiP, mtHsp60, Hsp70) occurred in the direct effect
      indicating that bleomycin might induce an arrest of transcription correlated with
      decreased survival. We observed the opposite trend in the bystander effect, with
      specific stress markers appearing increased and correlated with increased
      survival. These data shed new light on the potential role of stress pathways
      activation in bystander effects and their putative impact on the pro-survival pro
      death balance. 

PMID- 25771976
TI  - Analysis of the relationship between microsatellite instability and thymic
      lymphoma induced by N-methyl-N-nitrosourea in C57BL/6J mice.
AB  - Microsatellite instability (MSI) has been found to be closely associated with
      many types of human tumors and often shows strong correlations with specific
      tumor features. However, the relationship between MSI and tumors are still
      unclear. The aim of the present study is to explore the relationships between
      MSI, tumor formation under the mutagenic effects of N-methyl-N-nitrosourea (MNU).
      Mice were administered with either MNU (90 mg/kg) or PBS and DMSO (control) at
      the beginning of the 1st week of the experiment. Of the 31 mice that survived the
      entire experimental time course, 19 (61.3%) mice developed thymic lymphomas. In
      addition, 52.6% (10/19) of the tumors had metastasized to the liver. We detected
      MSI in MNU-treated mice using a panel of 42 mutation-sensitive loci. Nineteen
      loci (45.2%) in six organs showed 70 MSI events. Locus D8Mit14 showed enhanced
      MSI compared with the other examined loci. MSI frequency in thymus was higher
      than in other organs. Interestingly, there was no significant difference observed
      between the metastatic and non-metastatic livers. The MSI frequency (4.6%,
      23/(42*12)) in the MNU-treated thymus that had never developed tumor was
      significantly higher than this in the thymus that had developed lymphoma (0.5%,
      4/(42*19)) (p<0.0001). These results indicate that, although thymic tumorigenesis
      is associated with MSI, it occurs with higher frequency in these that have not
      developed tumors upon the MNU-treatment. Our study provides additional insights
      into the relationship between MSI occurrence and tumorigenesis.

PMID- 25771977
TI  - Inhibition of bladder cancer cell proliferation by allyl isothiocyanate (mustard
      essential oil).
AB  - Natural compounds hold great promise for combating antibiotic resistance, the
      failure to control some diseases, the emergence of new diseases and the toxicity
      of some contemporary medical products. Allyl isothiocyanate (AITC), which is
      abundant in cruciferous vegetables and mustard seeds and is commonly referred to
      as mustard essential oil, exhibits promising antineoplastic activity against
      bladder cancer, although its mechanism of action is not fully understood.
      Therefore, the aim of this study was to investigate the effects of AITC activity
      on bladder cancer cell lines carrying a wild type (wt; RT4) or mutated (T24) TP53
      gene. Morphological changes, cell cycle kinetics and CDK1, SMAD4, BAX, BCL2, ANLN
      and S100P gene expression were evaluated. In both cell lines, treatment with AITC
      inhibited cell proliferation (at 62.5, 72.5, 82.5 and 92.5MUM AITC) and induced
      morphological changes, including scattered and elongated cells and cellular
      debris. Gene expression profiles revealed increased S100P and BAX and decreased
      BCL2 expression in RT4 cells following AITC treatment. T24 cells displayed
      increased BCL2, BAX and ANLN and decreased S100P expression. No changes in SMAD4
      and CDK1 expression were observed in either cell line. In conclusion, AITC
      inhibits cell proliferation independent of TP53 status. However, the mechanism of
      action of AITC differed in the two cell lines; in RT4 cells, it mainly acted via
      the classical BAX/BCL2 pathway, while in T24 cells, AITC modulated the activities
      of ANLN (related to cytokinesis) and S100P. These data confirm the role of AITC
      as a potential antiproliferative compound that modulates gene expression
      according to the tumor cell TP53 genotype. 

PMID- 25771978
TI  - Novel characteristics of CtIP at damage-induced foci following the initiation of
      DNA end resection.
AB  - Homologous recombination (HR) is a major repair pathway for DNA double strand
      breaks (DSBs), and end resection, which generates a 3'-single strand DNA tail at
      the DSB, is an early step in the process. Resection is initiated by the Mre11
      nuclease together with CtIP. Here, we describe novel characteristics of CtIP at
      DSBs. At early times following exposure of human cells to ionizing radiation,
      CtIP localized to the DSB, became hyperphosphorylated and formed foci in an ATM
      dependent manner. At later times, when the initiation of resection had occurred,
      CtIP foci persist but CtIP is maintained in a hypophosphorylated state, which is
      dependent on ATM and ATR. Exposure to cycloheximide revealed that CtIP turns over
      at DSB sites downstream of resection. Our findings provide strong evidence that
      CtIP is continuously recruited to DSBs downstream of both the initiation and
      extension step of resection, strongly suggesting that CtIP has functions in
      addition to promoting the initiation of resection during HR. 

PMID- 25771979
TI  - Induction of DNA-protein cross-links by ionizing radiation and their elimination
      from the genome.
AB  - Ionizing radiation produces various types of DNA lesions, such as base damage,
      single-strand breaks, double-strand breaks (DSBs), and DNA-protein cross-links
      (DPCs). Of these, DSBs are the most critical lesions underlying the lethal
      effects of ionizing radiation. With DPCs, proteins covalently trapped in DNA
      constitute strong roadblocks to replication and transcription machineries, and
      hence can be lethal to cells. The formation of DPCs by ionizing radiation is
      promoted in the absence of oxygen, whereas that of DSBs is retarded. Accordingly,
      the contribution of DPCs to the lethal events in irradiated cells may not be
      negligible for hypoxic cells, such as those present in tumors. However, the role
      of DPCs in the lethal effects of ionizing radiation remains largely equivocal. In
      the present study, normoxic and hypoxic mouse tumors were irradiated with X-rays
      [low linear energy transfer (LET) radiation] and carbon (C)-ion beams (high LET
      radiation), and the resulting induction of DPCs and DSBs and their removal from
      the genome were analyzed. X-rays and C-ion beams produced more DPCs in hypoxic
      tumors than in normoxic tumors. Interestingly, the yield of DPCs was slightly but
      statistically significantly greater (1.3- to 1.5-fold) for C-ion beams than for X
      rays. Both X-rays and C-ion beams generated two types of DPC that differed
      according to their rate of removal from the genome. This was also the case for
      DSBs. The half-lives of the rapidly removed components of DPCs and DSBs were
      similar (<1 h), but those of the slowly removed components of DPCs and DSBs were
      markedly different (3.9-5 h for DSBs versus 63-70 h for DPCs). The long half-life
      and abundance of the slowly removed DPCs render them persistent in DNA, which may
      impede DNA transactions and confer deleterious effects on cells in conjunction
      with DSBs.

PMID- 25771980
TI  - Telomere Chromatin Condensation Assay (TCCA): a novel approach to study
      structural telomere integrity.
AB  - Telomeres, the DNA-protein complexes located at the end of linear eukaryotic
      chromosomes are essential for genome stability. Improper higher-order chromatin
      organization at the chromosome ends can give rise to telomeric recombination and
      genomic instability. We report the development of an assay to quantify
      differences in the condensation of telomeric chromatin, thereby offering new
      opportunities to study telomere biology and stability. We have combined a DNA
      nuclease digestion with a quantitative PCR (qPCR) assay of telomeric DNA, which
      we term the Telomere Chromatin Condensation Assay (TCCA). By quantifying the
      relative quantities of telomeric DNA that are progressively digested with the
      exonuclease Bal 31 the method can discriminate between different levels of
      telomeric chromatin condensation. The structural chromatin packaging at telomeres
      shielded against exonuclease digestion delivered an estimate, which we term
      Chromatin Protection Factor (CPF) that ranged from 1.7 to 2.3 fold greater than
      that present in unpacked DNA. The CPF was significantly decreased when cell
      cultures were incubated with the DNA hypomethylating agent 5-azacytidine,
      demonstrating the ability of the TCCA assay to discriminate between packaging
      levels of telomeric DNA. 

PMID- 25771981
TI  - Step-wise and punctuated genome evolution drive phenotype changes of tumor cells.
AB  - The pattern of genome evolution can be divided into two phases: the step-wise
      continuous phase (step-wise clonal evolution, stable dominant clonal chromosome
      aberrations (CCAs), and low frequency of non-CCAs, NCCAs) and punctuated phase
      (marked by elevated NCCAs and transitional CCAs). Depending on the phase, system
      stresses (the diverse CIN promoting factors) may lead to the very different
      phenotype responses. To address the contribution of chromosome instability (CIN)
      to phenotype changes of tumor cells, we characterized CCAs/NCCAs of HeLa and
      HEK293 cells, and their derivatives after genotoxic stresses (a stable plasmid
      transfection, ectopic expression of cancer-associated CHI3L1 gene or treatment
      with temozolomide) by conventional cytogenetics, copy number alterations (CNAs)
      by array comparative genome hybridization, and phenotype changes by cell
      viability and soft agar assays. Transfection of either the empty vector pcDNA3.1
      or pcDNA3.1_CHI3L1 into 293 cells initiated the punctuated genome changes. In
      contrast, HeLa_CHI3L1 cells demonstrated the step-wise genome changes. Increased
      CIN correlated with lower viability of 293_pcDNA3.1 cells but higher colony
      formation efficiency (CFE). Artificial CHI3L1 production in 293_CHI3L1 cells
      increased viability and further contributed to CFE. The opposite growth
      characteristics of 293_CHI3L1 and HeLa_CHI3L1 cells were revealed. The effect and
      function of a (trans)gene can be opposite and versatile in cells with different
      genetic network, which is defined by genome context. Temozolomide treatment of
      293_pcDNA3.1 cells intensified the stochastic punctuated genome changes and CNAs,
      and significantly reduced viability and CFE. In contrast, temozolomide treatment
      of HeLa_CHI3L1 cells promoted the step-wise genome changes, CNAs, and increased
      viability and CFE, which did not correlate with the ectopic CHI3L1 production.
      Thus, consistent coevolution of karyotypes and phenotypes was observed. CIN as a
      driving force of genome evolution significantly influences growth characteristics
      of tumor cells and should be always taken into consideration during the different
      experimental manipulations. 

PMID- 25771983
TI  - Polymorphisms in factor V and antithrombin III gene in recurrent pregnancy loss:
      a case-control study in Indian population.
AB  - Recurrent pregnancy loss (RPL) can be caused due to diverse factors with
      thrombophilia being one of them. The association of various thrombophilic risk
      factors with RPL is inconsistent in different studies and the frequency of these
      risk factors in Indian population is obscure. Five hundred and eighty patients
      with either recurrent early miscarriage or a history of at least one late
      miscarriage were screened for deficiency of protein C (PC), protein S (PS),
      antithrombin III (AT), APC resistance and prothrombin 20210G > A mutation. APC
      resistance positive patients were typed for the factor V Leiden, factor V Hong
      Kong/Cambridge mutations, and HR2 haplotype. PstI and rs2227589 AT mutations were
      detected by direct sequencing. APC resistance (13.4 %) was detected to be most
      common in Indian RPL patients followed by PS (10.6 %), PC (9.8 %) and AT
      deficiency (4.31 %.). FV Leiden was shown to be associated with APC resistance
      while HR2 haplotype was not associated with APC resistance (p values: 0.0001 and
      0.327 respectively) and the increased risk of RPL. PstI and rs2227589
      polymorphisms were similar in patients and controls and not associated with AT
      deficiency in RPL. Our study emphasizes the presence of other contributory
      factors towards APC resistance rather than FV Leiden alone. This is the first
      Indian study where HR2 haplotype and rs2227589 are observed to be present in RPL
      population. Although not significant, occurrence of rs2227589 and FV HR2 in
      homozygous condition necessitates the study of these polymorphisms in a larger
      sample size. 

PMID- 25771982
TI  - Right ventricular failure due to chronic pressure load: What have we learned in
      animal models since the NIH working group statement?
AB  - Right ventricular (RV) failure determines outcome in patients with pulmonary
      hypertension, congenital heart diseases and in left ventricular failure. In 2006,
      the Working Group on Cellular and Molecular Mechanisms of Right Heart Failure of
      the NIH advocated the development of preclinical models to study the
      pathophysiology and pathobiology of RV failure. In this review, we summarize the
      progress of research into the pathobiology of RV failure and potential
      therapeutic interventions. The picture emerging from this research is that RV
      adaptation to increased afterload is characterized by increased contractility,
      dilatation and hypertrophy. Clinical RV failure is associated with progressive
      diastolic deterioration and disturbed ventricular-arterial coupling in the
      presence of increased contractility. The pathobiology of the failing RV shows
      similarities with that of the LV and is marked by lack of adequate increase in
      capillary density leading to a hypoxic environment and oxidative stress and a
      metabolic switch from fatty acids to glucose utilization. However, RV failure
      also has characteristic features. So far, therapies aiming to specifically
      improve RV function have had limited success. The use of beta blockers and
      sildenafil may hold promise, but new therapies have to be developed. The use of
      recently developed animal models will aid in further understanding of the
      pathobiology of RV failure and development of new therapeutic strategies. 

PMID- 25771984
TI  - Endovascular treatments for cerebral venous sinus thrombosis.
AB  - Cerebral venous sinus thrombosis (CVST) is an uncommon but potentially fatal
      condition. CVST usually occurs young adults with a female predominance. The
      current mainstay for treating CVST is anticoagulation with heparin. However, more
      aggressive interventions, endovascular treatment as an example, may be indicated
      in selected patients who are non-responsive to heparin and other anticoagulants.
      Endovascular approaches include catheter-based local chemical thrombolysis,
      balloon angioplasty and mechanical thrombectomy, all of which may rapidly
      recanalize the occluded venous sinus, restore the blood flow, reduce the
      increased intracranial pressure, and subsequently relieve the corresponding
      symptoms. However, as an invasive strategy, endovascular procedures per se may
      cause complications, such as intracranial hemorrhage, vessel dissection and
      pulmonary embolization, which may substantially decrease the benefit-risk ratio
      of the treatment. Due to the rareness of the condition and the limited indication
      of this invasive strategy, safety and efficacy of endovascular procedures in
      treating CVST are less feasible to be evaluated in large randomized clinical
      trails. Therefore, the evidences for justifying this treatment strategy are
      largely derived from case reports, cohort studies and clinical observations. 

PMID- 25771985
TI  - Factors Influencing Outpatient Cardiac Rehabilitation Attendance.
AB  - PURPOSE: In the current health climate, the length of stay of cardiac patients in
      hospital has been decreasing, and this has significantly reduced the time nurses
      and colleagues have for providing inpatient cardiac rehabilitation (CR). The
      purpose of this research was to determine if inpatient CR has an influence on
      outpatient cardiac rehabilitation attendance for women, Maori, and older people.
      METHODS: An audit of patients discharged from hospital between November 2011 and
      July 2012 with a diagnosis of acute coronary syndrome were sent a postal
      questionnaire. FINDINGS: The survey was completed by 143 people: 46% female, 12%
      Maori, and 70% > 65 years. Only 38% attended outpatient CR on discharge. Reasons
      for not attending included lack of referral to CR, and 61% understood only
      some/none of the information given to them while in hospital. The Cardiac
      Rehabilitation Coordinator most consistently recommended attendance, but this
      invitation was extended after discharge from hospital. CONCLUSIONS: Attendance at
      outpatient CR is low and may increase with an improved individualized plan of
      care including greater cultural considerations and attention to discharge
      planning. An automatic referral tool as well as following evidence-based
      guidelines for inpatient care may increase participation rates for CR. CLINICAL
      RELEVANCE: Nursing staff have the majority of contact with patients and it
      appears that very few nurses are discussing CR programs with their patients. The
      information to attend CR should be offered by all of the health professionals
      patients meet during their stay in hospital.

PMID- 25771986
TI  - In Situ Hybridization Analysis of miR-146b-5p and miR-21 in Thyroid Nodules:
      Diagnostic Implications.
AB  - Some thyroid nodules such as follicular adenomas (FAs), follicular variant of
      papillary thyroid carcinomas (FVPTCs), and follicular thyroid carcinomas (FTCs)
      exhibit similar clinical presentations and gross morphologic appearances. The
      differential diagnosis of these lesions is sometimes difficult based on
      morphologic, cytologic, or clinical features alone. miR-146b-5p and miR-21
      deregulation has been associated with progression and metastasis of thyroid
      cancers. However, the utility of in situ hybridization (ISH) to determine the
      cellular localization, diagnostic, and prognostic significance of miR-146b-5p and
      miR-21 expression in thyroid tumors has not been extensively analyzed. In order
      to examine the expression of miR-146b-5p and miR-21 in benign and malignant
      thyroid tissues and to determine if these microRNAs could be assigned to distinct
      histomorphological types of thyroid nodules, we analyzed miR-146b-5p and miR-21
      expression in thyroid nodules on tissue microarrays (TMAs) with 193 thyroid
      specimens by ISH. miR-146b-5p and miR-21 expression in thyroid tissues was also
      analyzed by quantitative reverse transcription-polymerase chain reaction (qRT
      PCR). miR-146b-5p was highly expressed (89%) in papillary thyroid carcinomas
      (PTCs) and 41% of FVPTC. The expression of miR-146b-5p was not expressed in most
      FTCs, anaplastic thyroid carcinomas (ATCs), poorly differentiated thyroid
      carcinomas (PDTCs), or FAs (7, 8, 0, and 0%, respectively). MiR-21 was
      overexpressed in 83% of ATCs, 79 % of PTCs, 34% of FVPTCs, and 19% of PDTCs. The
      expression of miR-21 was not expressed in most FAs (9%) or FTCs (4%). Normal
      thyroid tissues and most benign goiters were negative for miR-146b-5p and miR-21.
      qRT-PCR analysis supported the ISH findings. PTC cases with positive expression
      of miR-146b-5p and miR-21 had significantly poorer disease-free survival rates.
      Immunohistochemical staining for HBME-1 showed positive staining in PTCs (100 %)
      and FVPTCs (92 %) with a subset of FTC (40%) staining positive, while all FAs
      were negative. Since miR-146b-5p was mainly expressed in PTC including FVPTC and
      was not expressed in most FTC, PDTC, or ATC, it may serve as a useful diagnostic
      marker for PTC. ISH is a useful method to analyze microRNA expression in formalin
      fixed paraffin-embedded thyroid tissues.

PMID- 25771987
TI  - Combined papillary and mucoepidermoid carcinoma of the thyroid gland: a possible
      collision tumor diagnosed on fine-needle cytology. Report of a case with
      immunocytochemical and molecular correlations.
AB  - Fine-needle cytology (FNC) is frequently used to diagnose thyroid nodules
      discovered by palpation or imaging studies. Molecular tests on FNC material may
      increase its diagnostic accuracy. We report a case of a classic papillary thyroid
      carcinoma combined with a mucoepidermoid carcinoma correctly identified on FNC.
      The papillary component had a classic immunophenotype (CK19+, TTF1+), while the
      mucoepidermoid one was only focally CK19+. Point mutations (BRAF and RAS) and
      rearrangements (RET/PTC) of the papillary component have been also investigated
      on FNC samples, with resulting concurrent rearrangements of RET/PTC1 and
      RET/PTC3, but no point mutations. The histogenesis of combined papillary and
      mucoepidermoid carcinoma of the thyroid still remains partly unsettled, and
      further genomic studies are needed to shed some more light on this peculiar
      neoplasm. 

PMID- 25771988
TI  - Guanosine in a single stranded region of anticodon stem-loop tRNA models is prone
      to oxidatively generated damage resulting in dehydroguanidinohydantoin and
      spiroiminodihydantoin lesions.
AB  - Oxidation of RNA hairpin models corresponding to anticodon stem-loop (ASL) of
      transfer RNA led to RNA damage consisting solely of a unique loop guanine
      oxidation. Manganese porphyrin/oxone treatment of RNA resulted in
      dehydroguanidinohydantoin (DGh; major) and/or spiroiminodihydantoin (Sp) lesions.
      Ribose damage was not observed. This two-electron transfer oxidation reaction
      allowed the identification of guanine oxidation products for further study of RNA
      species carrying a unique lesion at a single G to investigate their biological
      impact. 

PMID- 25771989
TI  - Comprehensive transcriptome analysis of mesenchymal stem cells in elderly
      patients with osteoporosis.
AB  - OBJECTIVE: To explore the role of aging in the pathogenesis of osteoporosis,
      several differentially expressed genes (DEGs) and altered biological pathways
      were identified in mesenchymal stem cells (MSCs) in elderly patients with
      osteoporosis. METHODS: Raw data were downloaded from Gene Expression Omnibus
      database. A total of 14 human MSC samples were available, including five samples
      from elderly patients suffering from osteoporosis, five controls from young non
      osteoporotic donors and five controls from old non-osteoporotic donors. The DEGs
      were identified using LIMMA package among the three groups. Gene ontology and
      KEGG pathway analysis were carried out using DAVID. A protein-protein interaction
      (PPI) network of DEGs was constructed with STRING and then visualized with
      Cytoscape. RESULTS: A total of 3179 DEGs were screened, including 1071 up- and
      2108 down-regulated genes. Compared with young and old controls, 271 and 781
      genes were up-regulated in osteoporosis, respectively, and 17 genes were shared.
      Function and pathway enrichment showed that the up-regulated genes in
      osteoporosis were involved in extracellular matrix (ECM)-receptor interaction,
      focal adhesion and mammalian target of rapamycin signaling pathway. Moreover, a
      range of genes linked to cell adhesion, ECM-receptor interaction and cell cycle
      were revealed in the PPI network, such as transforming growth factor beta 1,
      insulin-like growth factor 2 and integrin beta 2. CONCLUSION: A number of DEGs
      and altered pathways were screened in osteoporosis. Our study provided insights
      into the role of aging in the pathogenesis of osteoporosis and some DEGs might be
      potential biomarkers for osteoporosis.

PMID- 25771990
TI  - Assessment of thyroid function and lipid profile in patients with postadolescent
      acne in a Mediterranean population from Turkey.
AB  - BACKGROUND: Postadolescent acne is defined as acne that is seen even after the
      age of 25 years, regardless of the age at onset. The causes of postadolescent
      acne have not been completely clarified up to now. Androgens are considered to be
      the major factor involved in pathogenesis. OBJECTIVE: We aimed to investigate the
      status of thyroid functions and lipid levels in patients with postadolescent acne
      and determine the effects of lifestyle and environmental factors on
      postadolescent acne in a Turkish population. METHODS: In total, 184 patients and
      82 healthy controls were enrolled in the study. Thyroid function and lipid
      profiles of all participants were analyzed. RESULTS: The mean age of patients was
      30.4 +/- 4.9 years (25-50). The mean age of control group was 30.0 +/- 4.4 years
      (25-40). Cigarette smoking was significantly associated with postadolescent acne
      (P < 0.001). No significant differences were observed between patients with
      postadolescent acne and control subjects in triglyceride, total cholesterol, and
      low-density lipoprotein cholesterol levels, thyroid hormone profiles, and thyroid
      ultrasound scans. High-density lipoprotein cholesterol levels were significantly
      decreased with postadolescent acne (P = 0.01). CONCLUSIONS: To our knowledge,
      this is the first study to investigate the thyroid functions and lipid profile in
      men and women with postadolescent acne. In this study, there was no relationship
      between thyroid functions and postadolescent acne. However, an association with
      low high-density lipoprotein cholesterol levels and postadolescent acne was
      detected. Further investigations with more patients in different populations are
      needed to determine the causes of postadolescent acne.

PMID- 25771991
TI  - Retrograde intramedullary nailing for the treatment of femoral medial condyle
      fracture nonunion.
AB  - An unicondylar fracture of the femur is uncommon and of the medial condyle more
      so. Open reduction and internal fixation of these fractures is most commonly
      performed with screws or plate and screws. Secure bone fixation is compromised by
      osteoporosis in elderly patients; additional measures may be required. We report
      the case of an elderly osteoporotic patient with a medial condyle fracture
      nonunion treated successfully through retrograde intramedullary nailing. A 78
      year-old osteoporotic woman suffered medial condyle fracture of the femur 9
      months before visiting our hospital. She had been treated conservatively, and the
      fracture demonstrated a complete nonunion with gross instability. The edge
      fragments appeared sclerotic, and the nonunion site was accompanied by a bony
      defect. Although fixation by a plate and screw is the standard method for the
      treatment of such fracture, we judged that stability would be difficult to
      achieve with this method due to the accompanying bony defect and osteoporosis.
      Thus, we performed open reduction and fixation by retrograde intramedullary
      nailing with the use of "condyle screw and nut" system, followed by bone
      grafting. Bony union was successfully obtained. The stability and range of motion
      of the knee were recovered, and the patient regained the ability to walk. We
      suggest the unique application of retrograde intramedullary nailing with condyle
      screw and nut for the treatment of specific, complex cases of femoral medial
      condyle fracture. 

PMID- 25771992
TI  - Brain-decoding fMRI reveals how wholes relate to the sum of parts.
AB  - The human brain performs many nonlinear operations in order to extract relevant
      information from local inputs. How can we observe and quantify these effects
      within and across large patches of cortex? In this paper, we discuss the
      application of multi-voxel pattern analysis (MVPA) in functional magnetic
      resonance imaging (fMRI) to address this issue. Specifically, we show how MVPA
      (i) allows to compare various possibilities of part combinations into wholes,
      such as taking the mean, weighted mean, or the maximum of responses to the parts;
      (ii) can be used to quantify the parameters of these combinations; and (iii) can
      be applied in various experimental paradigms. Through these procedures, fMRI
      helps to obtain a computational understanding of how local information is
      integrated into larger wholes in various cortical regions. 

PMID- 25771994
TI  - A neonatal perspective on Homo erectus brain growth.
AB  - The Mojokerto calvaria has been central to assessment of brain growth in Homo
      erectus, but different analytical approaches and uncertainty in the specimen's
      age at death have hindered consensus on the nature of H. erectus brain growth. We
      simulate average annual rates (AR) of absolute endocranial volume (ECV) growth
      and proportional size change (PSC) in H. erectus, utilizing estimates of H.
      erectus neonatal ECV and a range of ages for Mojokerto. These values are compared
      with resampled ARs and PSCs from ontogenetic series of humans, chimpanzees, and
      gorillas from birth to six years. Results are consistent with other studies of
      ECV growth in extant taxa. There is extensive overlap in PSC between all living
      species through the first postnatal year, with continued but lesser overlap
      between humans and chimpanzees to age six. Human ARs are elevated above those of
      apes, although there is modest overlap up to 0.50 years. Ape ARs overlap
      throughout the sequence, with gorillas slightly elevated over chimpanzees up to
      0.50 years. Simulated H. erectus PSCs can be found in all living species by 0.50
      years, and the median falls below the human and chimpanzee ranges after 2.5
      years. H. erectus ARs are elevated above those of all extant taxa prior to 0.50
      years, and after two years they fall out of the human range but are still above
      ape ranges. A review of evidence for the age at death of Mojokerto supports an
      estimate of around one year, indicating absolute brain growth rates in the lower
      half of the human range. These results point to secondary altriciality in H.
      erectus, implying that key human adaptations for increasing the energy budget of
      females may have been established by at least 1 Ma. 

PMID- 25771995
TI  - Clinical Development and Regulatory Approval of Acute Heart Failure Drugs in
      Japan : Editorial to: "Rationale and Design of Double-Blind, Randomized, Placebo
      Controlled Multicenter Trial on Efficacy of Early Initiation of Eplerenone
      Treatment in Patients with Acute Heart Failure (EARLIER)" by M. Asakura et al.

PMID- 25771996
TI  - Fabrication of controllable and stable In2O3 nanowire transistors using an
      octadecylphosphonic acid self-assembled monolayer.
AB  - The controllability and stability of nanowire transistor characteristics are
      essential for the development of low-noise and fast-switching nano-electronic
      devices. In this study, the positive shift of threshold voltage and the
      improvement of interface quality on In2O3 nanowire transistors were
      simultaneously achieved by using octadecylphosphonic acid (OD-PA) self-assembly.
      Following the chemical bond of OD-PA molecules on the surface of In2O3 nanowires,
      the threshold voltage was positively shifted to 2.95 V, and the noise amplitude
      decreased to approximately 87.5%. The results suggest that an OD-PA self
      assembled monolayer can be used to manipulate and stabilize the transistor
      characteristics of nanowire-based memory and display devices that require high
      sensitivity, low-noise, and fast-response. 

PMID- 25771997
TI  - Minimally invasive pediatric neurosurgery.
AB  - Advances in technology have facilitated the development of minimally invasive
      neurosurgical options for the treatment of pediatric neurological disease. This
      review seeks to familiarize pediatric neurologists with some of the techniques of
      minimally invasive pediatric neurosurgery, focusing on treatments for
      hydrocephalus, arachnoid cysts, intracranial mass lesions, and craniosynostosis. 

PMID- 25771998
TI  - Tuberous sclerosis complex: a survey of health care resource use and health
      burden.
AB  - PURPOSE: Tuberous sclerosis complex (TSC) is a multiorgan, autosomal-dominant
      genetic disorder with incomplete penetrance. METHODS: This analysis of a web
      based survey focuses on the clinical presentation, management, and associated
      burden of patients with TSC in the United States. RESULTS: A total of 676 TSC
      patients or caregivers responded. Both pediatric and adult patient groups
      experienced skin lesions (77% and 44%), seizures (77% and 24%), and kidney
      complications (33% and 25%) as well as other manifestations. Patient groups
      averaged 22 visits to a physician, nine procedures/tests, two emergency room
      visits, and two hospital admissions in the past year. Standardized tests were
      administered for health-related quality of life and TSC patients reported
      significantly worse mental health scores and better physical health scores
      compared to a normative sample of cancer patients. CONCLUSION: Results
      demonstrate that TSC is associated with significant clinical burden, resource
      utilization, and decreased mental health well-being.

PMID- 25771993
TI  - Fabricated Elastin.
AB  - The mechanical stability, elasticity, inherent bioactivity, and self-assembly
      properties of elastin make it a highly attractive candidate for the fabrication
      of versatile biomaterials. The ability to engineer specific peptide sequences
      derived from elastin allows the precise control of these physicochemical and
      organizational characteristics, and further broadens the diversity of elastin
      based applications. Elastin and elastin-like peptides can also be modified or
      blended with other natural or synthetic moieties, including peptides, proteins,
      polysaccharides, and polymers, to augment existing capabilities or confer
      additional architectural and biofunctional features to compositionally pure
      materials. Elastin and elastin-based composites have been subjected to diverse
      fabrication processes, including heating, electrospinning, wet spinning, solvent
      casting, freeze-drying, and cross-linking, for the manufacture of particles,
      fibers, gels, tubes, sheets and films. The resulting materials can be tailored to
      possess specific strength, elasticity, morphology, topography, porosity,
      wettability, surface charge, and bioactivity. This extraordinary tunability of
      elastin-based constructs enables their use in a range of biomedical and tissue
      engineering applications such as targeted drug delivery, cell encapsulation,
      vascular repair, nerve regeneration, wound healing, and dermal, cartilage, bone,
      and dental replacement. 

PMID- 25771999
TI  - Intravenous ketogenic diet therapy for treatment of the acute stage of super
      refractory status epilepticus in a pediatric patient.
AB  - BACKGROUND: A ketogenic diet has been used successfully to treat intractable
      epilepsy. However, the role of early intravenous initiation of ketogenic diet in
      the acute phase of super-refractory status epilepticus is not well-described.
      METHODS: An intravenous ketogenic diet was administered to a boy with super
      refractory status epilepticus. At 24 hours after intravenous ketogenic diet,
      moderate ketosis appeared, and thiamylal was successfully weaned at 70 hours
      after admission. RESULTS: An intravenous ketogenic regimen led to subsequent
      ketosis and seizure control in a child with super-refractory status epilepticus.
      CONCLUSION: Early induction of ketosis may be a novel strategy to effectively
      treat super-refractory status epilepticus. Although there are few data regarding
      the early use of intravenous ketogenic diet in the treatment of super-refractory
      status epilepticus, it may be considered an alternative option.

PMID- 25772001
TI  - Synthesis and photochemical applications of processable polymers enclosing
      photoluminescent carbon quantum dots.
AB  - Herein, we propose convenient routes to produce hybrid-polymers that covalently
      enclosed, or confined, N-doped carbon quantum dots (CQDs). We focus our attention
      on polyamide, polyurea-urethane, polyester, and polymethylmetacrylate polymers,
      some of the most common resources used to create everyday materials. These hybrid
      materials can be easily prepared and processed to obtain macroscopic objects of
      different shapes, i.e., fibers, transparent sheets, and bulky forms, where the
      characteristic luminescence properties of the native N-doped CQDs are preserved.
      More importantly we explore the potential use of these hybrid composites to
      achieve photochemical reactions as those of photoreduction of silver ions to
      silver nanoparticles (under UV-light), the selective photo-oxidation of
      benzylalcohol to the benzaldehyde (under vis-light), and the photocatalytic
      generation of H2 (under UV-light). 

PMID- 25772000
TI  - Osteogenesis and chondrogenesis of biomimetic integrated porous PVA/gel/V-n
      HA/pa6 scaffolds and BMSCs construct in repair of articular osteochondral defect.
AB  - A novel bi-layered osteochondral scaffold, including of PVA/Gel/V layer for the
      cartilage and n-HA/PA6 layer for the subchondral bone, has been proposed to
      evaluate the potential of the engineered of osteochondral grafts in repairing
      articular osteochondral defects in rabbits. The two different layers of the
      scaffolds were seeded with allogenic bone marrow-derived stem cells (BMSCs),
      which were chondrogenically and osteogenically induced respectively. The critical
      size osteochondral defects were created in the knees of adult rabbits. The
      defects were treated with cell-bi-layered constructs (Group A), bi-layered
      constructs (Group B) and untreated group C as control group. The adhesion,
      proliferation and differentiation of BMSCs were demonstrated by
      immunohistochemical staining and scanning electron microscopy (SEM) in vitro.
      Cell survival was tracked via fluorescent labeling in vivo. Overall, the porous
      PVA/Gel/V-n-HA/PA6 scaffold was compatible and had no negative effects on the
      BMSCs in vitro culture. The cell-bi-layered scaffolds showed superior repair
      results as compared to the control group using gross examination and histological
      assessment. With BMSCs implantation, the two different layers of the composite
      biomimetic scaffolds provided a suitable environment for cells to form respective
      tissue. Simultaneously, the RT-PCR results confirmed the expression of specific
      extracellular matrix (ECM) markers for cartilaginous or osteoid tissue. This
      investigation showed that the porous PVA/Gel/V-n-HA/PA6 scaffold is a potential
      matrix for treatment of osteochondral defects, and the method of using
      chondrogenically and osteogenically differentiated BMSCs as seed cells on each
      layer might be a promising strategy in repair of articular osteochondral defect
      due to enhanced chondrogenesis and osteogenesis.

PMID- 25772002
TI  - Uncommon presentations of common pancreatic neoplasms: a pictorial essay.
AB  - Pancreatic neoplasms are a wide group of solid and cystic lesions with different
      and often characteristic imaging features, clinical presentations, and
      management. Among solid tumors, ductal adenocarcinoma is the most common: it
      arises from exocrine pancreas, comprises about 90% of all pancreatic neoplasms,
      and generally has a bad prognosis; its therapeutic management must be
      multidisciplinary, involving surgeons, oncologists, gastroenterologists,
      radiologists, and radiotherapists. The second most common solid pancreatic
      neoplasms are neuroendocrine tumors: they can be divided into functioning or non
      functioning and present different degrees of malignancy. Cystic pancreatic
      neoplasms comprise serous neoplasms, which are almost always benign, mucinous
      cystic neoplasms and intraductal papillary mucinous neoplasms, which can vary
      from benign to frankly malignant lesions, and solid pseudopapillary tumors. Other
      pancreatic neoplasms, such as lymphoma, metastases, or pancreatoblastoma, are
      rarely seen in clinical practice and have different and sometimes controversial
      managements. Rare clinical presentations and imaging appearance of the most
      common pancreatic neoplasms, both solid and cystic, are more frequently seen and
      clinically relevant than rare pancreatic tumors; their pathologic and radiologic
      appearances must be known to improve their management. The purpose of this paper
      is to present some rare or uncommon clinical and radiological presentations of
      common pancreatic neoplasms providing examples of multi-modality imaging approach
      with pathologic correlations, thus describing the histopathological bases that
      can explain the peculiar imaging features, in order to avoid relevant
      misdiagnosis and to improve lesion management. 

PMID- 25772003
TI  - A Video Feedback Intervention for Workforce Development: Exploring Staff
      Perspective Using Longitudinal Qualitative Methodology.
AB  - BACKGROUND: In this study, we explored the impact of staff training that used
      video feedback to help staff see the effect of their interactional work with
      service users. The study was based at a large organization delivering services
      for children and adults with autism. MATERIALS AND METHODS: A longitudinal
      qualitative study with semi-structured interviews was conducted to explore
      changes over time in 10 staff participants who received the intervention. Five
      participants were interviewed twice before they received the video feedback
      intervention to gauge the degree to which their perspective changed as part of
      the natural course of their working lives. RESULTS: The results showed that the
      staff talked differently after they had the intervention. The most notable change
      was their talk about the service user perspective which was evident after the
      intervention but not before. CONCLUSIONS: The outcomes suggest that the use of
      video feedback of in situ practice could help staff develop person-centred work
      practices.

PMID- 25772004
TI  - Prioritization of pharmaceuticals for potential environmental hazard through
      leveraging a large-scale mammalian pharmacological dataset.
AB  - The potential for pharmaceuticals in the environment to cause adverse ecological
      effects is of increasing concern. Given the thousands of active pharmaceutical
      ingredients (APIs) that can enter the aquatic environment through human and/or
      animal (e.g., livestock) waste, a current challenge in aquatic toxicology is
      identifying those that pose the greatest risk. Because empirical toxicity
      information for aquatic species is generally lacking for pharmaceuticals, an
      important data source for prioritization is that generated during the mammalian
      drug development process. Applying concepts of species read-across, mammalian
      pharmacokinetic data were used to systematically prioritize APIs by estimating
      their potential to cause adverse biological consequences to aquatic organisms,
      using fish as an example. Mammalian absorption, distribution, metabolism, and
      excretion (ADME) data (e.g., peak plasma concentration, apparent volume of
      distribution, clearance rate, and half-life) were collected and curated, creating
      the Mammalian Pharmacokinetic Prioritization For Aquatic Species Targeting
      (MaPPFAST) database representing 1070 APIs. From these data, a probabilistic
      model and scoring system were developed and evaluated. Individual APIs and
      therapeutic classes were ranked based on clearly defined read-across assumptions
      for translating mammalian-derived ADME parameters to estimate potential hazard in
      fish (i.e., greatest predicted hazard associated with lowest mammalian peak
      plasma concentrations, total clearance and highest volume of distribution, half
      life). It is anticipated that the MaPPFAST database and the associated API
      prioritization approach will help guide research and/or inform ecological risk
      assessment.

PMID- 25772005
TI  - Collective unconscious: how gut microbes shape human behavior.
AB  - The human gut harbors a dynamic and complex microbial ecosystem, consisting of
      approximately 1 kg of bacteria in the average adult, approximately the weight of
      the human brain. The evolutionary formation of a complex gut microbiota in
      mammals has played an important role in enabling brain development and perhaps
      sophisticated social interaction. Genes within the human gut microbiota, termed
      the microbiome, significantly outnumber human genes in the body, and are capable
      of producing a myriad of neuroactive compounds. Gut microbes are part of the
      unconscious system regulating behavior. Recent investigations indicate that these
      microbes majorly impact on cognitive function and fundamental behavior patterns,
      such as social interaction and stress management. In the absence of microbes,
      underlying neurochemistry is profoundly altered. Studies of gut microbes may play
      an important role in advancing understanding of disorders of cognitive
      functioning and social interaction, such as autism. 

PMID- 25772006
TI  - Cordance derived from REM sleep EEG as a biomarker for treatment response in
      depression--a naturalistic study after antidepressant medication.
AB  - OBJECTIVE: To evaluate whether prefrontal cordance in theta frequency band
      derived from REM sleep EEG after the first week of antidepressant medication
      could characterize the treatment response after 4 weeks of therapy in depressed
      patients. METHOD: 20 in-patients (15 females, 5 males) with a depressive episode
      and 20 healthy matched controls were recruited into 4-week, open label, case
      control study. Patients were treated with various antidepressants. No significant
      differences in age (responders (mean +/- SD): 45 +/- 22) years; non-responders:
      49 +/- 12 years), medication or Hamilton Depression Rating Scale (HAM-D) score
      (responders: 23.8 +/- 4.5; non-responders 24.5 +/- 7.6) at inclusion into the
      study were found between responders and non-responders. Response to treatment was
      defined as a >=50% reduction of HAM-D score at the end of four weeks of active
      medication. Sleep EEG of patients was recorded after the first and the fourth
      week of medication. Cordance was computed for prefrontal EEG channels in theta
      frequency band during tonic REM sleep. RESULTS: The group of 8 responders had
      significantly higher prefrontal theta cordance in relation to the group of 12 non
      responders after the first week of antidepressant medication. This finding was
      significant also when controlling for age, gender and number of previous
      depressive episodes (F1,15 = 6.025, P = .027). Furthermore, prefrontal cordance
      of all patients showed significant positive correlation (r = 0.52; P = .019) with
      the improvement of HAM-D score between the inclusion week and fourth week of
      medication. CONCLUSIONS: The results suggest that prefrontal cordance derived
      from REM sleep EEG could provide a biomarker for the response to antidepressant
      treatment in depressed patients.

PMID- 25772007
TI  - Intratracheal administration of mitochondrial DNA directly provokes lung
      inflammation through the TLR9-p38 MAPK pathway.
AB  - An increasing number of studies have focused on the phenomenon that mitochondrial
      DNA (mtDNA) activates innate immunity responses. However, the specific role of
      mtDNA in inflammatory lung disease remains elusive. This study was designed to
      examine the proinflammatory effects of mtDNA in lungs and to investigate the
      putative mechanisms. C57BL/6 mice were challenged intratracheally with mtDNA with
      or without pretreatment with chloroquine. Changes in pulmonary histopathology,
      cytokine concentrations, and phosphorylation levels of p38 MAPK were assayed at
      four time points. In in vitro experiments, THP-1 macrophages were pretreated or
      not pretreated with chloroquine, TLR9 siRNA, p38 MAPK siRNA, or SB203580 and then
      incubated with mtDNA. The levels of cytokines and p-p38 MAPK were detected by
      ELISA and Western blot, respectively. The intratracheal administration of mtDNA
      induced infiltration of inflammatory cells, production of proinflammatory
      cytokines (including IL-1beta, IL-6, and TNF-alpha), and activation of p38 MAPK.
      The chloroquine pretreatment resulted in an abatement of mtDNA-induced local lung
      inflammation. In vitro experiments showed that the exposure of THP-1 macrophages
      to mtDNA also led to a significant upregulation of IL-1beta, IL-6, and TNF-alpha
      and the activation of p38 MAPK. And these responses were inhibited either by
      chloroquine and TLR9 siRNA or by SB203580 and p38 MAPK siRNA pretreatment. The
      intratracheal administration of mtDNA induced a local inflammatory response in
      the mouse lung that depended on the interactions of mtDNA with TLR9 and may be
      correlated with infiltrating macrophages that could be activated by mtDNA
      exposure via the TLR9-p38 MAPK signal transduction pathway. 

PMID- 25772008
TI  - Lycopene bioavailability is associated with a combination of genetic variants.
AB  - The intake of tomatoes and tomato products, which constitute the main dietary
      source of the red pigment lycopene (LYC), has been associated with a reduced risk
      of prostate cancer and cardiovascular disease, suggesting a protective role of
      this carotenoid. However, LYC bioavailability displays high interindividual
      variability. This variability may lead to varying biological effects following
      LYC consumption. Based on recent results obtained with two other carotenoids, we
      assumed that this variability was due, at least in part, to several single
      nucleotide polymorphisms (SNPs) in genes involved in LYC and lipid metabolism.
      Thus, we aimed at identifying a combination of SNPs significantly associated with
      the variability in LYC bioavailability. In a postprandial study, 33 healthy male
      volunteers consumed a test meal containing 100g tomato puree, which provided 9.7
      mg all-trans LYC. LYC concentrations were measured in plasma chylomicrons (CM)
      isolated at regular time intervals over 8 h postprandially. For the study 1885
      SNPs in 49 candidate genes, i.e., genes assumed to play a role in LYC
      bioavailability, were selected. Multivariate statistical analysis (partial least
      squares regression) was used to identify and validate the combination of SNPs
      most closely associated with postprandial CM LYC response. The postprandial CM
      LYC response to the meal was notably variable with a CV of 70%. A significant
      (P=0.037) and validated partial least squares regression model, which included 28
      SNPs in 16 genes, explained 72% of the variance in the postprandial CM LYC
      response. The postprandial CM LYC response was also positively correlated to
      fasting plasma LYC concentrations (r=0.37, P<0.05). The ability to respond to LYC
      is explained, at least partly, by a combination of 28 SNPs in 16 genes.
      Interindividual variability in bioavailability apparently affects the long-term
      blood LYC status, which could ultimately modulate the biological response
      following LYC supplementation.

PMID- 25772009
TI  - Light-induced disulfide dimerization of recoverin under ex vivo and in vivo
      conditions.
AB  - Despite vast knowledge of the molecular mechanisms underlying photochemical
      damage of photoreceptors, linked to progression of age-related macular
      degeneration, information on specific protein targets of the light-induced
      oxidative stress is scarce. Here, we demonstrate that prolonged intense
      illumination (halogen bulb, 1500 lx, 1-5 h) of mammalian eyes under ex vivo (cow)
      or in vivo (rabbit) conditions induces disulfide dimerization of recoverin, a
      Ca(2+)-dependent inhibitor of rhodopsin kinase. Western blotting and mass
      spectrometry analysis of retinal extracts reveals illumination time-dependent
      accumulation of disulfide homodimers of recoverin and its higher order disulfide
      cross-linked species, including a minor fraction of mixed disulfides with
      intracellular proteins (tubulins, etc.). Meanwhile, monomeric bovine recoverin
      remains mostly reduced. These effects are accompanied by accumulation of
      disulfide homodimers of visual arrestin. Histological studies demonstrate that
      the light-induced oxidation of recoverin and arrestin occurs in intact retina
      (illumination for 2 h), while illumination for 5 h is associated with damage of
      the photoreceptor layer. A comparison of ex vivo levels of disulfide homodimers
      of bovine recoverin with redox dependence of its in vitro thiol-disulfide
      equilibrium (glutathione redox pair) gives the lowest estimate of redox potential
      in rod outer segments under illumination from -160 to -155 mV. Chemical
      crosslinking and dynamic light scattering data demonstrate an increased
      propensity of disulfide dimer of bovine recoverin to multimerization/aggregation.
      Overall, the oxidative stress caused by the prolonged intense illumination of
      retina might affect rhodopsin desensitization via concerted disulfide
      dimerization of recoverin and arrestin. The developed herein models of eye
      illumination are useful for studies of the light-induced thiol oxidation of
      visual proteins.

PMID- 25772010
TI  - Reinterpreting the best biomarker of oxidative stress: The 8-iso
      PGF(2alpha)/PGF(2alpha) ratio distinguishes chemical from enzymatic lipid
      peroxidation.
AB  - The biomarker 8-iso-prostaglandin F2alpha (8-iso-PGF2alpha) is regarded as the
      gold standard for detection of excessive chemical lipid peroxidation in humans.
      However, biosynthesis of 8-iso-PGF2alpha via enzymatic lipid peroxidation by
      prostaglandin-endoperoxide synthases (PGHSs), which are significantly induced in
      inflammation, could lead to incorrect biomarker interpretation. To resolve the
      ambiguity with this biomarker, the ratio of 8-iso-PGF2alpha to prostaglandin
      F2alpha (PGF2alpha) is established as a quantitative measure to distinguish
      enzymatic from chemical lipid peroxidation in vitro, in animal models, and in
      humans. Using this method, we find that chemical lipid peroxidation contributes
      only 3% to the total 8-iso-PGF2alpha in the plasma of rats. In contrast, the 8
      iso-PGF2alpha levels in plasma of human males are generated >99% by chemical
      lipid peroxidation. This establishes the potential for an alternate pathway of
      biomarker synthesis, and draws into question the source of increases in 8-iso
      PGF2alpha seen in many human diseases. In conclusion, increases in 8-iso
      PGF2alpha do not necessarily reflect increases in oxidative stress; therefore,
      past studies using 8-iso-PGF2alpha as a marker of oxidative stress may have been
      misinterpreted. The 8-iso-PGF2alpha/PGF2alpha ratio can be used to distinguish
      biomarker synthesis pathways and thus confirm the potential change in oxidative
      stress in the myriad of disease and chemical exposures known to induce 8-iso
      PGF2alpha. 

PMID- 25772011
TI  - Antioxidant cytoprotection by peroxisomal peroxiredoxin-5.
AB  - Peroxiredoxin-5 (PRDX5) is a thioredoxin peroxidase that reduces hydrogen
      peroxide, alkyl hydroperoxides, and peroxynitrite. This enzyme is present in the
      cytosol, mitochondria, peroxisomes, and nucleus in human cells. Antioxidant
      cytoprotective functions have been previously documented for cytosolic,
      mitochondrial, and nuclear mammalian PRDX5. However, the exact function of PRDX5
      in peroxisomes is still not clear. The aim of this work was to determine the
      function of peroxisomal PRDX5 in mammalian cells and, more specifically, in glial
      cells. To study the role of PRDX5 in peroxisomes, the endogenous expression of
      PRDX5 in murine oligodendrocyte 158N cells was silenced by RNA interference. In
      addition, human PRDX5 was also overexpressed in peroxisomes using a vector coding
      for human PRDX5, whose unconventional peroxisomal targeting sequence 1 (PTS1;
      SQL) was replaced by the prototypical PTS1 SKL. Stable 158N clones were obtained.
      The antioxidant cytoprotective function of peroxisomal PRDX5 against peroxisomal
      and mitochondrial KillerRed-mediated reactive oxygen species production as well
      as H2O2 was examined using MTT viability assays, roGFP2, and C11-BOBIPY probes.
      Altogether our results show that peroxisomal PRDX5 protects 158N oligodendrocytes
      against peroxisomal and mitochondrial KillerRed- and H2O2-induced oxidative
      stress. 

PMID- 25772012
TI  - Dioscin ameliorates cerebral ischemia/reperfusion injury through the
      downregulation of TLR4 signaling via HMGB-1 inhibition.
AB  - We previously reported the promising effect of dioscin against hepatic
      ischemia/reperfusion (I/R) injury, but its effect on cerebral I/R injury remains
      unknown. In this work, an in vitro oxygen-glucose deprivation and reoxygenation
      (OGD/R) model and an in vivo middle cerebral artery occlusion (MCAO) model were
      used. The results indicated that dioscin clearly protected PC12 cells and primary
      cortical neurons against OGD/R insult and significantly prevented cerebral I/R
      injury. Further research demonstrated that dioscin-induced neuroprotection was
      accompanied by a significant inhibition in the expression and the nuclear to
      cytosolic translocation of HMGB-1, reflected by decreased TLR4 expression.
      Blockade of the TLR4/MyD88/TRAF6 signaling pathway by dioscin inhibited NF-kappaB
      and AP-1 transcriptional activities, MAPK and STAT3 phosphorylation, and pro
      inflammatory cytokine responses, and upregulated the levels of anti-inflammatory
      factors. In addition, small interfering RNA (siRNA) and overexpressed genes of
      HMGB-1 and TLR4 were applied in in vitro experiments, respectively, and the
      results further confirmed that dioscin showed an efficient neuroprotection
      because of its inhibiting effects on HMGB-1/TLR4 signaling and subsequent
      suppressing inflammation. These findings provide new insights that will aid in
      elucidating the effect of dioscin against cerebral I/R injury and support the
      development of dioscin as a potential treatment for ischemic stroke. 

PMID- 25772013
TI  - Opsoclonus-ataxia syndrome associated with ovarian mature teratoma.
AB  - A 16-year-old girl with no prior medical history developed vertigo and nausea
      following alimentary infection. Neurological examination showed limb and truncal
      ataxia, opsoclonus, myoclonus, and hyperreflexia. Brain magnetic resonance
      imaging and cerebrospinal fluid analysis showed no abnormalities. Treatment with
      i.v. high-dose methylprednisolone and immunoglobulin was started, but this proved
      ineffective. The clinical course was unusual, so whole-body computed tomography
      was done to evaluate other differential diagnoses. Imaging identified right
      ovarian mature teratoma. Paraneoplastic opsoclonus-ataxia syndrome was suspected,
      therefore single-incision laparoscopic ovarian cystectomy was done 10 days after
      admission. Two months after therapy, the patient had complete recovery and
      remained asymptomatic at 1 year after onset. Serum testing for anti-neuronal
      antibodies was negative, including for anti-N-methyl-d-aspartate-receptor
      antibody. Young women with ataxia and opsoclonus of unclear etiology should be
      examined for the presence of ovarian teratoma, then intensive immunotherapy and
      prompt tumor resection can lead to good clinical outcome. 

PMID- 25772014
TI  - Quantitative analysis of transcranial and intraparenchymal light penetration in
      human cadaver brain tissue.
AB  - BACKGROUND AND OBJECTIVE: Photobiomodulation (PBM) also known as low-level light
      therapy has been used successfully for the treatment of injury and disease of the
      nervous system. The use of PBM to treat injury and diseases of the brain requires
      an in-depth understanding of light propagation through tissues including scalp,
      skull, meninges, and brain. This study investigated the light penetration
      gradients in the human cadaver brain using a Transcranial Laser System with a 30
      mm diameter beam of 808 nm wavelength light. In addition, the wavelength
      dependence of light scatter and absorbance in intraparenchymal brain tissue using
      660, 808, and 940 nm wavelengths was investigated. STUDY DESIGN/MATERIAL AND
      METHODS: Intact human cadaver heads (n = 8) were obtained for measurement of
      light propagation through the scalp/skull/meninges and into brain tissue. The
      cadaver heads were sectioned in either the transverse or mid-sagittal. The
      sectioned head was mounted into a cranial fixture with an 808 nm wavelength laser
      system illuminating the head from beneath with either pulsed-wave (PW) or
      continuous-wave (CW) laser light. A linear array of nine isotropic optical fibers
      on a 5 mm pitch was inserted into the brain tissue along the optical axis of the
      beam. Light collected from each fiber was delivered to a multichannel power
      meter. As the array was lowered into the tissue, the power from each probe was
      recorded at 5 mm increments until the inner aspect of the dura mater was reached.
      Intraparenchymal light penetration measurements were made by delivering a series
      of wavelengths (660, 808, and 940 nm) through a separate optical fiber within the
      array, which was offset from the array line by 5 mm. Local light penetration was
      determined and compared across the selected wavelengths. RESULTS: Unfixed cadaver
      brains provide good anatomical localization and reliable measurements of light
      scatter and penetration in the CNS tissues. Transcranial application of 808 nm
      wavelength light penetrated the scalp, skull, meninges, and brain to a depth of
      approximately 40 mm with an effective attenuation coefficient for the system of
      2.22 cm(-1) . No differences were observed in the results between the PW and CW
      laser light. The intraparenchymal studies demonstrated less absorption and
      scattering for the 808 nm wavelength light compared to the 660 or 940 nm
      wavelengths. CONCLUSIONS: Transcranial light measurements of unfixed human
      cadaver brains allowed for determinations of light penetration variables. While
      unfixed human cadaver studies do not reflect all the conditions seen in the
      living condition, comparisons of light scatter and penetration and estimates of
      fluence levels can be used to establish further clinical dosing. The 808 nm
      wavelength light demonstrated superior CNS tissue penetration.

PMID- 25772015
TI  - The potential participation of abdominal pressure in preeclampsia.
AB  - Preeclampsia is a major cause of maternal and perinatal mortality and morbidity.
      Regardless of susceptibility or predisposing conditions and risk factors, the
      degree of increase in abdominal pressure is directly related to the severity of
      preeclampsia, particularly in women with hydatidiform mole. When increased
      abdominal pressure is normalized by delivery, preeclampsia is cured. Recent
      genetic studies highlighted two leading risk factors for preeclampsia: chronic
      renal disease and T235 homozygosity for the AGT gene. Thus, while there is
      increased abdominal pressure in pregnancy, an imbalanced renin angiotensin system
      and renal injuries lead to a vicious cycle of increasing abdominal pressure and
      further renal injuries. A hypothesis for the potential participation of pressure
      in preeclampsia is described and the amelioration of preeclampsia through
      postural intervention and the possible therapeutic effect of angiotensin is
      suggested.

PMID- 25772016
TI  - ISOLATION AND FUNCTIONAL ANALYSIS OF McMenA, A GENE ENCODING A 1,4-DIHYDROXY-2
      NAPHTHOATE OCTAPRENYLTRANSFERASE IN Mylabris cichorii.
AB  - Cantharidin is a biomolecule with a role in host defense that can also be used as
      an anticancer drug. The in vivo biosynthetic pathway for cantharidin has been the
      subject of debate for several decades and the mechanism is not yet completely
      understood. To study the biosynthetic pathway of cantharidin in blister beetles,
      Mylabris cichori, a full-length MenA (McMenA) cDNA was cloned based on the
      partial sequence of the MenA gene from a suppression subtractive hybridization
      (SSH) library of male and female adult M. cichorii. The cDNA was 1264 base pairs
      (bp) with an open reading frame of 1026 bp nucleotides encoding a 341 amino acid
      protein. Analysis of the McMenA amino acid sequence showed that the aspartate
      rich motif N/DDxxD represented binding sites for prenyl diphosphate via a Mg(2+)
      ion. Phylogenetic analysis showed that McMenA was most closely related to MenA of
      Tribolium castaneum, and the amino acid sequence similarity was 86%. The
      expression pattern of McMenA in adults was analyzed using RT-qPCR, and we found
      that the highest expression of McMenA occurred during 22-25 days in the sex
      separate breeding males, while the lowest expression occurred in females at the
      same time. Injection with a specific double-strand RNA (dsRNA) of McMenA led to a
      significant reduction of McMenA mRNA levels after 24 h. Cantharidin and ATP
      concentrations dropped around the same time. Together, our data showed that the
      McMenA gene might be involved in cantharidin biosynthesis.

PMID- 25772017
TI  - Determination of base binding strength and base stacking interaction of DNA
      duplex using atomic force microscope.
AB  - As one of the most crucial properties of DNA, the structural stability and the
      mechanical strength are attracting a great attention. Here, we take advantage of
      high force resolution and high special resolution of Atom Force Microscope and
      investigate the mechanical force of DNA duplexes. To evaluate the base pair
      hydrogen bond strength and base stacking force in DNA strands, we designed two
      modes (unzipping and stretching) for the measurement rupture forces. Employing k
      means clustering algorithm, the ruptured force are clustered and the mean values
      are estimated. We assessed the influence of experimental parameters and performed
      the force evaluation for DNA duplexes of pure dG/dC and dA/dT base pairs. The
      base binding strength of single dG/dC and single dA/dT were estimated to be 20.0
      +/- 0.2 pN and 14.0 +/- 0.3 pN, respectively, and the base stacking interaction
      was estimated to be 2.0 +/- 0.1 pN. Our results provide valuable information
      about the quantitative evaluation of the mechanical properties of the DNA
      duplexes.

PMID- 25772018
TI  - Expression analysis of GSK-3beta in diapause pupal brains in the cotton bollworm,
      Helicoverpa armigera.
AB  - Diapause is an adaptive response to adverse environmental conditions, but the
      molecular mechanisms are unclear. Some signaling molecules have been identified
      in the regulation of diapause. GSK-3beta is an important signaling protein
      involved in several signaling pathways. In this study, GSK-3beta from the cotton
      bollworm, Helicoverpa armigera, was cloned using reverse transcription polymerase
      chain reaction and rapid amplification of complementary DNA (cDNA) ends
      techniques. Sequence analysis showed that the full-length cDNA was 1447 bp
      containing a 292 bp 5'-untranslated region (UTR), a 162 bp 3'-UTR and a 993 bp
      open reading frame (ORF). The deduced Har-GSK-3beta protein has high identity to
      other known GSK-3beta, as determined by Basic Local Alignment Search Tool
      analysis. Developmental expression of total GSK-3beta and p-GSK-3beta (Ser9) in
      diapause and non-diapause pupal brains was investigated by Western blotting.
      Results indicated that the activity of GSK-3beta is down-regulated in diapause
      pupal brains, which is further confirmed by Western blotting after diapause
      break. These finding suggest that the down-regulation of Har-GSK-3beta activity
      may be important for pupal diapause. 

PMID- 25772019
TI  - Time Trends of Left Ventricular Ejection Fraction and Myocardial Deformation
      Indices in a Cohort of Women with Breast Cancer Treated with Anthracyclines,
      Taxanes, and Trastuzumab.
AB  - BACKGROUND: Trastuzumab, a HER2 monoclonal antibody, has transformed the
      prognosis of patients with the aggressive HER2-positive breast cancer type.
      Trastuzumab augments the cardiotoxic effects of anthracyclines, but its effect is
      thought to be at least partially reversible. The objective of this study was to
      examine the time trends of left ventricular (LV) size and function in a cohort of
      women treated with anthracyclines and trastuzumab. METHODS: Twenty-nine patients
      >18 years of age with first-time breast cancer treated with anthracyclines and
      trastuzumab were monitored using echocardiography before, at the completion of,
      and at a median follow-up of 24.7 months (interquartile range, 15.9-34 months)
      after the end of their cancer treatment. LV volume, LV ejection fraction, and
      global peak systolic longitudinal strain and strain rate were measured in the
      apical four- and two-chamber views. Left ventricular ejection fraction was
      measured using a modified Simpson's biplane method. RESULTS: LV end-diastolic and
      end-systolic volumes increased at the end of treatment compared with baseline and
      did not recover during follow-up. Left ventricular ejection fraction, strain, and
      strain rate decreased at the end of treatment compared with baseline (from 64 +/-
      6% to 59 +/- 8%, from -20.0 +/- 2.5% to -17.6 +/- 2.6%, and from -1.26 +/- 0.23
      to -1.13 +/- 0.16 sec(-1), respectively; P < .05 for all parameters) and remained
      decreased at follow-up. CONCLUSIONS: LV dilation and subclinical impairment in
      cardiac function persists >2 years after the end of anthracycline and trastuzumab
      treatment, without significant recovery after trastuzumab cessation, suggestive
      of long-term underlying cardiac damage and remodeling.

PMID- 25772020
TI  - Percutaneous closure of perivalvular mitral regurgitation: how should the
      interventionalists and the echocardiographers communicate?
AB  - There is considerable interest in percutaneous closure of perivalvular leaks
      without the need for repeat surgery. Successful percutaneous closure of these
      defects requires extensive planning and coordination before and during the
      procedure. However, there is no standardized description of valve pathology in
      the presence of a prosthetic valve, which adds to the challenge of communication.
      Transesophageal echocardiography is ideally suited to guide percutaneous mitral
      valve procedures, because of the proximity of the mitral valve to the esophagus.
      Successful percutaneous procedures of the mitral valve require teamwork. Both the
      interventionalist and the echocardiographer must have great familiarity with
      mitral valve anatomy, structure, and function, and they must know how to
      effectively communicate with each other. The authors review the relevant
      periprocedural mapping of the mitral valve and provide guidance to
      echocardiographers and interventionalists on effective ways to communicate during
      percutaneous perivalvular mitral leak closures to accomplish a successful
      outcome. 

PMID- 25772021
TI  - Ovarian torsion after laparoscopic ovarian transposition in patients with
      gynecologic cancer: a report of two cases.
AB  - Ovarian transposition has proven to be a safe method for preserving ovarian
      function in young premenopausal women who require pelvic irradiation for
      treatment of early stage malignancies. We report 2 cases of ovarian torsion after
      laparoscopic ovarian transposition in 2 young women scheduled for chemotherapy
      and radiation therapy for treatment of cervical or vaginal cancer. We believe
      these are the first such cases reported in the literature. In discussions with
      patients regarding the risks and potential benefits of ovarian transposition,
      ovarian torsion should be included as a possible, although rare, complication. 

PMID- 25772022
TI  - Robotic-assisted Abdominal Cerclage Placement During Pregnancy and Its
      Challenges.
AB  - STUDY OBJECTIVE: To demonstrate a surgical video of 2 cases, in which the steps
      of robotic-assisted abdominal cerclage placement were delineated in one and a
      uterine vessel injury was repaired in the other. DESIGN: Step-by-step explanation
      of the technique using a surgical video (Canadian Task Force classification III).
      SETTING: The procedures were performed at a teaching hospital. The first patient
      was a 25-year-old gravida 4 para 0, with a history of cervical incompetence, who
      was 13 weeks pregnant at the time of surgery. She had failed McDonald cerclage
      and was referred for abdominal cerclage placement. The second patient was a 32
      year-old gravida 6 para 0 who was 15 weeks pregnant. She had a history of 3
      second-trimester miscarriages with painless cervical dilation and had failed
      McDonald cerclage during her previous pregnancy. Both patients were taken to the
      operating room for robotic-assisted abdominal cerclage placement early in the
      second trimester. INTERVENTIONS: Robotic-assisted abdominal cerclage placement
      was performed with ultrasound guidance. The procedure was begun with formation of
      the bladder flap [1]. An avascular space between the ascending and descending
      branches of uterine artery, at the level of the cervicoisthmic junction, was
      subsequently developed. The Mersilene tape was passed through this space in a
      posterior-to-anterior direction and pulled taut until it was laid flat along the
      posterior uterine wall. Six knots were then placed with the Mersilene tape on the
      anterior aspect of the uterus. The free ends of the tape were trimmed and
      approximated with a nonabsorbable suture to prevent knot slippage. The
      vesicouterine reflection was then reapproximated, and correct cerclage placement
      was confirmed with transvaginal ultrasound. In the second case, an incidental
      uterine vessel injury occurred during development of the avascular space.
      Hemostasis was attained immediately by clamping the vessel with the fenestrated
      graspers. Permanent hemostasis required application of the vascular clips,
      proximally and distally on the lacerated arterial site. CONCLUSION: A robotic
      approach was chosen for our patients requiring transabdominal cerclage placement
      during pregnancy, in an attempt to decrease the surgical morbidity associated
      with laparotomy [2,3]. Despite the challenges introduced by the enlarged gravid
      uterus, both procedures were successfully completed, and the patients delivered
      at term via cesarean section.

PMID- 25772023
TI  - Implementing Housing First Across Sites and Over Time: Later Fidelity and
      Implementation Evaluation of a Pan-Canadian Multi-site Housing First Program for
      Homeless People with Mental Illness.
AB  - This article examines later fidelity and implementation of a five-site pan
      Canadian Housing First research demonstration project. The average fidelity score
      across five Housing First domains and 10 programs was high in the first year of
      operation (3.47/4) and higher in the third year of operation (3.62/4).
      Qualitative interviews (36 key informant interviews and 17 focus groups) revealed
      that staff expertise, partnerships with other services, and leadership
      facilitated implementation, while staff turnover, rehousing participants,
      participant isolation, and limited vocational/educational supports impeded
      implementation. The findings shed light on important implementation "drivers" at
      the staff, program, and community levels. 

PMID- 25772024
TI  - Efficacy of pegylated interferon and ribavirin combination therapy for patients
      with hepatitis C virus infection after curative resection or ablation for
      hepatocellular carcinoma--A retrospective multicenter study.
AB  - The use of pegylated interferon (Peg-IFN) plus ribavirin combination therapy for
      chronic hepatitis C patients who received curative treatment for hepatocellular
      carcinoma is controversial. This study tried to clarify this. Ninety-nine chronic
      hepatitis C patients who received curative resection or radiofrequency ablation
      for primary hepatocellular carcinoma, met the Milan criteria and were treated
      with Peg-IFN plus ribavirin therapy were enrolled (75 males, 24 females; mean
      age, 65.0 +/- 5.9 years; 79 HCV genotype 1, 20 genotype 2). Among them, 40
      patients who had received curative treatment for a single carcinoma were analyzed
      for recurrence (observation period: 27.6 +/- 18.1 months). The factors associated
      with recurrence were examined using a log-rank test and a Cox proportional
      hazards model. The discontinuation rate of the Peg-IFN plus ribavirin combination
      therapy was 25% (25/99). Among the patients who completed the therapy, the
      sustained virologic response rates were 35% for the genotype 1 patients and 56%
      for the genotype 2 patients. The cumulative incidence rates of recurrence were
      10.0% at 1 year and 40.8% at 3 years. On multivariate analysis, a virologic
      response and platelet counts served as independent factors of recurrence
      (sustained virologic response, hazard ratio = 0.190, P = 0.029; platelet counts
      <12 * 10(4) /mm(3), hazard ratio = 3.19, P = 0.019). It is concluded that
      patients with chronic hepatitis C virus infection after curative treatment for
      hepatocellular carcinoma can be candidates for anti-viral therapy to reduce the
      recurrence of hepatocellular carcinoma, especially patients with low platelet
      counts.

PMID- 25772025
TI  - Evaluating the Accuracy of Cranial Indices in Ancestry Estimation Among South
      African Groups.
AB  - Historically, population differences were quantified using cranial indices. Even
      though the application of indices is associated with numerous statistical and
      methodological problems, the use of cranial indices to estimate ancestry persists
      as demonstrated by its inclusion in several recent papers and conference
      presentations. The purpose of this study was to classify 207 South African crania
      and compare the results of five standard cranial indices to linear discriminant
      analysis (LDA). New sectioning points were created to contend with low
      classification accuracies (40-79%) and possible secular trends. Although the
      accuracies of the new sectioning points increased (66-87%), the accuracies
      associated with the stepwise LDA were higher (84%) and could classify the crania
      into one of the three South African groups. The results of the study demonstrate
      that indices cannot compete with multivariate techniques and should not be used
      in forensic anthropological analyses for ancestry estimation. 

PMID- 25772026
TI  - Effect of genetic profiling on prediction of therapeutic resistance and survival
      in adult acute myeloid leukemia.

PMID- 25772028
TI  - Routine Screening for High Blood Pressure Outside of Primary Care: An Idea Whose
      Time Has Come.

PMID- 25772029
TI  - Plumbagin Nanoparticles Induce Dose and pH Dependent Toxicity on Prostate Cancer
      Cells.
AB  - Stable nano-formulation of Plumbagin nanoparticles from Plumbago zeylanica root
      extract was explored as a potential natural drug against prostate cancer. Size
      and morphology analysis by DLS, SEM and AFM revealed the average size of
      nanoparticles prepared was 100+/-50nm. In vitro cytotoxicity showed concentration
      and time dependent toxicity on prostate cancer cells. However, plumbagin crude
      extract found to be highly toxic to normal cells when compared to plumbagin
      nanoformulation, thus confirming nano plumbagin cytocompatibility with normal
      cells and dose dependent toxicity to prostate cells. In vitro hemolysis assay
      confirmed the blood biocompatibility of the plumbagin nanoparticles. In wound
      healing assay, plumbagin nanoparticles provided clues that it might play an
      important role in the anti-migration of prostate cancer cells. DNA fragmentation
      revealed that partial apoptosis induction by plumbagin nanoparticles could be
      expected as a potent anti-cancer effect towards prostate cancer. 

PMID- 25772027
TI  - Primary graft failure after myeloablative allogeneic hematopoietic cell
      transplantation for hematologic malignancies.
AB  - Clinical outcomes after primary graft failure (PGF) remain poor. Here we present
      a large retrospective analysis (n=23,272) which investigates means to prevent PGF
      and early detection of patients at high risk. In patients with hematologic
      malignancies, who underwent their first myeloablative allogeneic hematopoietic
      cell transplantation, PGF was reported in 1278 (5.5%), and there was a marked
      difference in PGFs using peripheral blood stem cell compared with bone marrow
      grafts (2.5 vs 7.3%; P<0.001). A fourfold increase of PGF was observed in
      myeloproliferative disorders compared with acute leukemia (P<0.001). Other risk
      factors for PGF included recipient age <30, HLA mismatch, male recipients of
      female donor grafts, ABO incompatibility, busulfan/cyclophosphamide conditioning
      and cryopreservation. In bone marrow transplants, total nucleated cell doses ?2.4
      * 10(8) per kg were associated with PGF (odds ratio 1.39; P<0.001). The use of
      tacrolimus-based immunosuppression and granulocyte colony-stimulating factor were
      associated with decreased PGF risk. These data, allow clinicians to do more
      informed choices with respect to graft source, donor selection, conditioning and
      immunosuppressive regimens to reduce the risk of PGF. Moreover, a novel risk
      score determined on day 21 post transplant may provide the rationale for an early
      request for additional hematopoietic stem cells.

PMID- 25772030
TI  - Warming differentially influences the effects of drought on stoichiometry and
      metabolomics in shoots and roots.
AB  - Plants in natural environments are increasingly being subjected to a combination
      of abiotic stresses, such as drought and warming, in many regions. The effects of
      each stress and the combination of stresses on the functioning of shoots and
      roots have been studied extensively, but little is known about the simultaneous
      metabolome responses of the different organs of the plant to different stresses
      acting at once. We studied the shift in metabolism and elemental composition of
      shoots and roots of two perennial grasses, Holcus lanatus and Alopecurus
      pratensis, in response to simultaneous drought and warming. These species
      responded differently to individual and simultaneous stresses. These responses
      were even opposite in roots and shoots. In plants exposed to simultaneous drought
      and warming, terpenes, catechin and indole acetic acid accumulated in shoots,
      whereas amino acids, quinic acid, nitrogenous bases, the osmoprotectants choline
      and glycine betaine, and elements involved in growth (nitrogen, phosphorus and
      potassium) accumulated in roots. Under drought, warming further increased the
      allocation of primary metabolic activity to roots and changed the composition of
      secondary metabolites in shoots. These results highlight the plasticity of plant
      metabolomes and stoichiometry, and the different complementary responses of
      shoots and roots to complex environmental conditions. 

PMID- 25772031
TI  - Clinical and in vitro evidence for the antimicrobial therapy in Burkholderia
      cepacia complex infections.
AB  - Treatment of infections caused by Burkholderia cepacia complex (Bcc) in cystic
      fibrosis (CF) patients poses a complex problem. Bcc is multidrug-resistant due to
      innate and acquired mechanisms of resistance. As CF patients receive multiple
      courses of antibiotics, susceptibility patterns of strains from CF patients may
      differ from those noted in strains from non-CF patients. Thus, there was a need
      for assessing in vitro and clinical data to guide antimicrobial therapy in these
      patients. A systematic search of literature, followed by extraction and analysis
      of available information from human and in vitro studies was done. The results of
      the analysis are used to address various aspects like use of antimicrobials for
      pulmonary and non-pulmonary infections, use of combination versus monotherapy,
      early eradication, duration of therapy, route of administration, management of
      biofilms, development of resistance during therapy, pharmacokinetics
      pharmacodynamics correlations, therapy in post-transplant patients and newer
      drugs in Bcc-infected CF patients. 

PMID- 25772032
TI  - Validation of a Web-based, self-administered, non-consecutive-day dietary record
      tool against urinary biomarkers.
AB  - New technologies are promising for the use of short-term instruments for dietary
      data collection; however, innovative tools should be validated against objective
      biomarkers. The aim of the present study was to investigate the validity of a Web
      based, self-administered dietary record (DR) tool using protein, K and Na intakes
      against 24 h urinary biomarkers (24 h U). Of the total participants, 199 adult
      volunteers (104 men and 95 women, mean age 50.5 (23-83 years)) of the NutriNet
      Sante Study were included in the protocol. They completed three non-consecutive
      day DR and two 24 h U on the first and third DR days. Relative differences
      between reported (DR) and measured (24 h U) intakes were calculated from the log
      ratio (DR/24 h U) for protein, K and Na intakes: -14.4,+2.6 and -2.1 % for men;
      and -13.9, -3.7 and -8.3 % for women, respectively. The correlations between
      reported and true intakes were 0.61, 0.78 and 0.47 for men and 0.64, 0.42 and
      0.37 for women for protein, K and Na, respectively. Attenuation factors, that
      represent attenuation of the true diet-disease relationship due to measurement
      error (a value closer to 1 indicating lower attenuation), ranged from 0.23 (Na,
      women) to 0.60 (K, men). We showed that the Web-based DR tool used in the
      NutriNet-Sante cohort study performs well in estimating protein and K intakes and
      fairly well in estimating Na intake. Furthermore, three non-consecutive-day DR
      appear to be valid for estimating usual intakes of protein and K, although
      caution is advised regarding the generalisability of these findings to other
      nutrients and general population.

PMID- 25772033
TI  - Predictors of underestimation of malignancy after image-guided core needle biopsy
      diagnosis of flat epithelial atypia or atypical ductal hyperplasia.
AB  - Flat epithelial atypia (FEA) and atypical ductal hyperplasia (ADH) are precursors
      of breast malignancy. Management of FEA or ADH after image-guided core needle
      biopsy (CNB) remains controversial. The aim of this study was to evaluate
      malignancy underestimation rates after FEA or ADH diagnosis using image-guided
      CNB and to identify clinical characteristics and imaging features associated with
      malignancy as well as identify cases with low underestimation rates that may be
      treatable by observation only. We retrospectively reviewed 2,875 consecutive
      image-guided CNBs recorded in an electronic data base from January 2010 to
      December 2011 and identified 128 (4.5%) FEA and 83 (2.9%) ADH diagnoses (211
      total cases). Of these, 64 (30.3%) were echo-guided CNB procedures and 147
      (69.7%) mammography-guided CNBs. Twenty patients (9.5%) were upgraded to
      malignancy. Multivariate analysis indicated that age (OR = 1.123, p = 0.002,
      increase of 1 year), mass-type lesion with calcifications (OR = 8.213, p =
      0.006), and ADH in CNB specimens (OR = 8.071, p = 0.003) were independent
      predictors of underestimation. In univariate analysis of echo-guided CNB (n =
      64), mass with calcifications had the highest underestimation rate (p < 0.001).
      Multivariate analysis of 147 mammography-guided CNBs revealed that age (OR =
      1.122, p = 0.040, increase of 1 year) and calcification distribution were
      significant independent predictors of underestimation. No FEA case in which,
      complete calcification retrieval was recorded after CNB was upgraded to
      malignancy. Older age at diagnosis on image-guided CNB was a predictor of
      malignancy underestimation. Mass with calcifications was more likely to be
      associated with malignancy, and in cases presenting as calcifications only,
      segmental distribution or linear shapes were significantly associated with
      upgrading. Excision after FEA or ADH diagnosis by image-guided CNB is warranted
      except for FEA diagnosed using mammography-guided CNB with complete calcification
      retrieval.

PMID- 25772034
TI  - Advances in non-invasive techniques as aids to the diagnosis and monitoring of
      therapeutic response in plaque psoriasis: a review.
AB  - Plaque psoriasis is a common, chronic, inflammatory disease with a multifactorial
      etiopathogenesis. Although its diagnosis is often based on clinical features, in
      ambiguous cases a biopsy with histopathologic confirmation may be necessary.
      Advanced high-definition imaging techniques may be useful in the study of skin
      properties in vivo and may facilitate therapeutic monitoring. Available imaging
      tools vary in their resolution, depth of penetration and visual representation
      (horizontal, vertical, three-dimensional), and in the type of skin structures
      visualized. The purpose of this review is to analyze a variety of non-invasive
      techniques that may assist in establishing definitive diagnoses, as well as in
      the therapeutic monitoring of psoriasis. These include dermoscopy,
      videocapillaroscopy (VC), high-frequency ultrasound (HFUS), reflectance confocal
      microscopy (RCM), laser Doppler imaging (LDI), optical coherence tomography
      (OCT), optical microangiography (OMAG) and multiphoton tomography (MPT). Their
      characteristics, indications, advantages, and limits are reviewed and discussed.
      Dermoscopy may be useful for a first, rapid outpatient evaluation.
      Videocapillaroscopy and HFUS represent the imaging techniques with the longest
      history of use in psoriasis. However, whereas VC is useful in both diagnosis and
      therapeutic monitoring, the utility of HFUS appears to be limited to the
      monitoring of response to therapy only. Both devices are cost-effective and easy
      to use in the office setting. Both RCM and OCT allow high-resolution microscopic
      imaging of psoriatic plaque in a manner comparable with that of virtual
      histopathology and represent more promising techniques. The utility of LDI, OMAG,
      and MPT in psoriasis skin imaging requires further study and validation. 

PMID- 25772035
TI  - Liver-directed gene therapy of chronic hepadnavirus infection using interferon
      alpha tethered to apolipoprotein A-I.
AB  - BACKGROUND & AIMS: Current hepatitis B virus (HBV) management is challenging as
      treatment with nucleos(t)ide analogues needs to be maintained indefinitely and
      because interferon (IFN)-alpha therapy is associated with considerable toxicity.
      Previously, we showed that linking IFNalpha to apolipoprotein A-I generates a
      molecule (IA) with distinct antiviral and immunostimulatory activities which
      lacks the hematological toxicity of IFNalpha. METHODS: Here, we analyse the
      antiviral potential of an adeno-associated vector encoding IFNalpha fused to
      apolipoprotein A-I (AAV-IA) in comparison to a vector encoding only IFNalpha (AAV
      IFN) in two animal models of chronic hepadnavirus infection. RESULTS: In HBV
      transgenic mice, we found that both vectors induced marked reductions in serum
      and liver HBV DNA and in hepatic HBV RNA but AAV-IFN caused lethal pancytopenia.
      Woodchucks with chronic hepatitis virus (WHV) infection that were treated by
      intrahepatic injection of vectors encoding the woodchuck sequences (AAV-wIFN or
      AAV-wIA), experienced only a slight reduction of viremia which was associated
      with hematological toxicity and high mortality when using AAV-wIFN, while AAV-wIA
      was well tolerated. However, when we tested AAV-wIA or a control vector encoding
      woodchuck apolipoprotein A-I (AAV-wApo) in combination with entecavir, we found
      that AAV-wApo-treated animals exhibited an immediate rebound of viral load upon
      entecavir withdrawal while, in AAV-wIA-treated woodchucks, viremia and
      antigenemia remained at low levels for several weeks following entecavir
      interruption. CONCLUSIONS: Treatment with AAV-IA is safe and elicits antiviral
      effects in animal models with difficult to treat chronic hepadnavirus infection.
      AAV-IA in combination with nucleos(t)ide analogues represents a promising
      approach for the treatment of HBV infection in highly viremic patients.

PMID- 25772036
TI  - Sarcopaenia is associated with NAFLD independently of obesity and insulin
      resistance: Nationwide surveys (KNHANES 2008-2011).
AB  - BACKGROUND & AIMS: Although sarcopaenia is associated with obesity-related
      comorbidities, its influence on non-alcoholic fatty liver disease (NAFLD) or
      steatohepatitis has not been fully determined. We aimed to investigate the direct
      relationship between sarcopaenia and NAFLD or steatohepatitis in the general
      population. METHODS: We conducted a cross-sectional study using nationally
      representative samples of 15,132 subjects from the Korea National Health and
      Nutrition Examination Surveys 2008-2011. Subjects were defined as having NAFLD
      when they had higher scores from previously validated NAFLD prediction models
      such as the hepatic steatosis index, comprehensive NAFLD score and NAFLD liver
      fat score. BARD and FIB-4 scores were used to define advanced fibrosis in
      subjects with NAFLD. The skeletal muscle index (SMI) [SMI(%)=total appendicular
      skeletal muscle mass (kg)/weight (kg)*100] measured by dual-energy X-ray
      absorptiometry was used to diagnose sarcopaenia with cut points of 32.2% for men
      and 25.5% for women. RESULTS: SMI was inversely correlated with all NAFLD
      predicting scores (Ps<0.001). After stratification, sarcopaenic subjects had an
      increased risk of NAFLD regardless of obesity (odds ratios [ORs]=1.55 to 3.02,
      depending on models; all Ps<0.001) or metabolic syndrome (ORs=1.63 to 4.00, all
      Ps<0.001). Multiple logistic regression analysis also demonstrated this
      independent association between sarcopaenia and NAFLD after adjusting for
      confounding factors related to obesity or insulin resistance (ORs=1.18 to 1.22,
      all Ps<0.001). Furthermore, among the NAFLD population, subjects with lower SMIs
      were likely to have advanced fibrosis compared with non-sarcopaenic individuals
      (BARD and FIB-4: ORs=1.83 and 1.69, respectively; both Ps<0.001). Compared with
      non-exercised subjects, individuals who exercised regularly had a lower risk of
      NAFLD (p<0.001), particularly among obese people with well-preserved muscle mass.
      CONCLUSIONS: Sarcopaenia is associated with increased risks of NAFLD and advanced
      fibrosis, independent of obesity or metabolic control.

PMID- 25772037
TI  - Intrahepatic cholestasis of pregnancy and cancer, immune-mediated and
      cardiovascular diseases: A population-based cohort study.
AB  - BACKGROUND & AIMS: Intrahepatic cholestasis of pregnancy (ICP) is the most common
      liver disease in pregnancy. It is associated with hepatobiliary diseases that
      might predispose to cancer and also with gestational diabetes and preeclampsia.
      In this study, we examined associations between ICP and cancer, and immune
      mediated and cardiovascular diseases. METHODS: By linking the Swedish Medical
      Birth Register and the Swedish Patient Register, we identified 11,388 women with
      ICP and 113,893 matched women without ICP who gave birth between 1973 and 2009.
      Diagnoses of cancer and immune-mediated and cardiovascular diseases both before
      and after delivery were obtained from the Patient Register. The main outcome
      measures were hazard ratios (HRs), calculated through Cox regression, for the
      indicated diseases after delivery. RESULTS: ICP was not associated with later
      overall cancer (HR 1.07, 95% confidence interval [CI] 0.94-1.21), but it was
      associated with later liver and biliary tree cancer (HR 3.61, 95% CI 1.68-7.77,
      and 2.62, 95% CI 1.26-5.46, respectively). ICP was also associated with later
      immune-mediated diseases (HR 1.28, 95% CI 1.19-1.38), and specifically diabetes
      mellitus (HR 1.47, 95% CI 1.26-1.72), thyroid disease (HR 1.30, 95% CI 1.14
      1.47), psoriasis (HR 1.27, 95% CI 1.07-1.51), inflammatory polyarthropathies (HR
      1.32, 95% CI 1.11-1.58) and Crohn's disease (HR 1.55, 95% CI 1.14-2.10), but not
      ulcerative colitis (HR 1.21, 95% CI 0.93-1.58). Women with ICP also had a small
      increased risk of later cardiovascular disease (HR 1.12, 95% CI 1.06-1.19).
      CONCLUSIONS: Women with ICP have increased risk of later hepatobiliary cancer and
      immune-mediated and cardiovascular diseases.

PMID- 25772038
TI  - Biology of the immunomodulatory molecule HLA-G in human liver diseases.
AB  - The non-classical human leukocyte antigen-G (HLA-G), plays an important role in
      inducing tolerance, through its immunosuppressive effects on all types of immune
      cells. Immune tolerance is a key issue in the liver, both in liver homeostasis
      and in the response to liver injury or cancer. It would therefore appear likely
      that HLA-G plays an important role in liver diseases. Indeed, this molecule was
      recently shown to be produced by mast cells in the livers of patients infected
      with hepatitis C virus (HCV). Furthermore, the number of HLA-G-positive mast
      cells was significantly associated with fibrosis progression. The generation of
      immune tolerance is a role common to both HLA-G, as a molecule, and the liver, as
      an organ. This review provides a summary of the evidence implicating HLA-G in
      liver diseases. In the normal liver, HLA-G transcripts can be detected, but there
      is no HLA-G protein. However, HLA-G protein is detectable in the liver tissues
      and/or plasma of patients suffering from hepatocellular carcinoma, hepatitis B or
      C, or visceral leishmaniasis and in liver transplant recipients. The cells
      responsible for producing HLA-G differ between diseases. HLA-G expression is
      probably induced by microenvironmental factors, such as cytokines. The expression
      of HLA-G receptors, such as ILT2, ILT4, and KIRD2L4, on liver cells has yet to be
      investigated, but these receptors have been detected on all types of immune
      cells, and such cells are present in liver. The tolerogenic properties of HLA-G
      explain its deleterious effects in cancers and its beneficial effects in
      transplantation. Given the key role of HLA-G in immune tolerance, new therapeutic
      agents targeting HLA-G could be tested for the treatment of these diseases in the
      future. 

PMID- 25772039
TI  - Comparative Tissue Stainability of Lawsonia inermis (Henna) and Eosin as
      Counterstains to Hematoxylin in Brain Tissues.
AB  - We hyposthesized that henna staining could provide an alternative to eosin when
      used as a counterstain to hematoxylin for understanding basic neurohistological
      principles. Therefore, this study was aimed at investigating the suitability of
      henna as counterstain to hematoxylin for the demonstration of the layer
      stratification and cellular distribution in the brain tissue. Henna stained
      nervous tissue by reacting with the basic elements in proteins via its amino
      groups. It stained the neuropil and connective tissue membranes brown and
      effectively outlined the perikarya of neurons with no visible nuclei
      demonstrating that it is an acidic dye. Henna as a counterstain to hematoxylin
      demonstrated reliability as a new neurohistological stain. It facilitated
      identification of cortical layer stratification and cellular distribution in
      brain tissue sections from Wistar rats. This was comparable to standard
      hematoxylin and eosin staining as morphological and morphometrical analyses of
      stained cells did not show significant differences in size or number. This study
      presents a method for staining with henna and demonstrates that although henna
      and eosin belong to different dye groups (anthraquinone and xanthenes,
      respectively) based on their chromophores, they share similar staining techniques
      and thus could be used interchangeably in neurohistology. 

PMID- 25772040
TI  - Development of a novel in vitro onychomycosis model for the evaluation of topical
      antifungal activity.
AB  - A novel in vitro onychomycosis model was developed to easily predict the topical
      activity potential of novel antifungal drugs. The model encompasses drug activity
      and diffusion through bovine hoof slices in a single experimental set-up. Results
      correspond well with the antifungal susceptibility assay and Franz cell diffusion
      test. 

PMID- 25772041
TI  - From Mice to Men: TRPC3 in Cerebellar Ataxia.
AB  - The dominantly inherited cerebellar ataxias are a clinically and genetically
      heterogeneous group of neurodegenerative disorders. Studies using mouse models as
      well as recent genetic and transcriptomic human findings point to an important
      role for TRPC3 signaling in cerebellar ataxia.

PMID- 25772043
TI  - Recurrent gastrointestinal perforation in a patient with Ehlers-Danlos syndrome
      due to tenascin-X deficiency.
AB  - Ehlers-Danlos syndrome (EDS) is a clinically and genetically heterogeneous
      disorder. Using a customized targeted exome-sequencing system we identified
      nonsense mutations in TNXB in a patient who had recurrent gastrointestinal
      perforation due to tissue fragility. This case highlights the utility of targeted
      exome sequencing for the diagnosis of congenital diseases showing genetic
      heterogeneity, and the importance of attention to gastrointestinal perforation in
      patients with tenascin-X deficient type EDS. 

PMID- 25772042
TI  - Characterization of a potato activation-tagged mutant, nikku, and its partial
      revertant.
AB  - MAIN CONCLUSION: A potato mutant with a strong stress-response phenotype, and a
      partial mutant revertant, were characterized. Gene expression patterns and DNA
      cytosine methylation varied between these and wild-type, indicating a role for
      DNA cytosine methylation changes in the gene expression and visible phenotypes.
      Morphological and molecular studies were conducted to compare potato cv. Bintje,
      a Bintje activation-tagged mutant (nikku), and nikku revertant phenotype plants.
      Morphological studies revealed that nikku plants exhibited an extremely dwarf
      phenotype, had small hyponastic leaves, were rootless, and infrequently produced
      small tubers compared to wild-type Bintje. The overall phenotype was suggestive
      of a constitutive stress response, which was further supported by the greater
      expression level of several stress-responsive genes in nikku. Unlike the nikku
      mutant, the revertant exhibited near normal shoot elongation, larger leaves and
      consistent rooting. The reversion appeared partial, and was not the result of a
      loss of 35S enhancer copies from the original nikku mutant. Southern blot
      analyses indicated the presence of a single T-DNA insertion on chromosome 12 in
      the mutant. Gene expression studies comparing Bintje, nikku and revertant
      phenotype plants indicated transcriptional activation/repression of several genes
      flanking both sides of the insertion in the mutant, suggesting that activation
      tagging had pleiotropic effects in nikku. In contrast, gene expression levels for
      many, but not all, of the same genes in the revertant were similar to Bintje,
      indicating some reversion at the gene expression level as well. DNA methylation
      studies indicated differences in cytosine methylation status of the 35S enhancers
      between the nikku mutant and its revertant. In addition, global DNA cytosine
      methylation varied between Bintje, the nikku mutant and the revertant, suggesting
      involvement in gene expression changes, as well as mutant phenotype.

PMID- 25772044
TI  - Use of an absorbable adhesion barrier for reconstruction of partial mastectomy
      defects in the upper quadrant of large ptotic breasts.
AB  - INTRODUCTION: An absorbable adhesion barrier (Interceed((r))) is generally used
      during gynecologic or pelvic surgery. We report a new oncoplastic technique using
      the absorbable Interceed((r)) sheet for upper quadrant breast cancer in large
      ptotic breasts with no other flaps. MATERIALS AND METHODS: From January 2007 to
      June 2013, a total of 25 patients with breast cancer underwent conventional
      breast-conserving surgery with the Interceed((r)) sheet insertion technique.
      Tumors were removed with oncologically safe margins, and adjacent breast tissue
      was repositioned to adjust the breast's shape. When shaping was completed, the
      breast skin turgor was strengthened using Burrow's triangle displacement
      technique. Interceed((r)) was then placed between breast skin and pectoralis
      muscle fascia with four-quadrant anchoring sutures. RESULTS: The tumors were
      located in the upper central (n = 12), upper inner (n = 11), and upper outer (n =
      2) quadrants. The mean weight of the removed breasts was 82.1 g, and the mean
      operative time was 161.3 min. There were two postoperative complications-a wound
      infection and fat necrosis-which were resolved with conservative management.
      Radiation-induced fibrosis and skin thickening were identified by magnetic
      resonance imaging 8-12 weeks after radiotherapy. Overall patient and surgeon
      satisfaction with the cosmetic results were evaluated as excellent (n = 12), good
      (n = 11), or fair (n = 2). CONCLUSION: Use of the absorbable Interceed((r)) sheet
      during surgery for upper quadrant breast cancer is feasible in patients with
      large ptotic breasts.

PMID- 25772045
TI  - pANCA positivity predicts lower clinical response to infliximab therapy among
      patients with IBD.
AB  - OBJECTIVES: Several studies have been performed evaluating the role of
      perinuclear anti-neutrophil cytoplasmic antibodies (pANCA) to predict early
      clinical response among patients with inflammatory bowel disease (IBD) who are
      undergoing infliximab therapy. The results of these studies are variable,
      however, and the effect of pANCA+ as a predictor of clinical response to
      infliximab remains largely undefined. The goal of this meta-analysis was to
      evaluate the role of pANCA in predicting poor responders to infliximab. METHODS:
      A comprehensive search of the PubMed/MEDLINE, Scopus, Cumulative Index of Nursing
      and Allied Health Literature, Google Scholar, and Cochrane databases was
      performed in June 2014. All of the studies that evaluated pANCA levels in
      patients with IBD who were undergoing antitumor necrosis factor-alpha (anti-TNF
      alpha) therapy and their clinical responses were included. A meta-analysis was
      performed using the Mantel-Haenszel model with odds ratios to assess for clinical
      remission. RESULTS: In the pooled analysis (N = 415), patients who were pANCA
      negative had nearly a twofold higher response to anti-TNF-alpha therapy compared
      with patients who were pANCA+ (odds ratio 1.87; 95% confidence interval 1.02
      3.41). Serologic testing for pANCA+ predicting nonresponse to infliximab therapy
      showed a sensitivity of 25.2%, a specificity of 85.5%, a positive predictive
      value of 41.1%, and a negative predictive value of 74.0%. CONCLUSIONS: Being more
      proactive (ie, early dose escalation or accelerated loading regimen) in patients
      who are pANCA+ may be necessary to improve clinical response.

PMID- 25772046
TI  - Commentary on "pANCA positivity predicts lower clinical response to infliximab
      therapy among patients with IBD".

PMID- 25772047
TI  - Rules for improving pharmacotherapy in older adult patients: part 2 (rules 6-10).
AB  - The population of older adult patients in the United States is growing each year.
      Appropriate pharmacotherapy has allowed many older patients to live longer and
      maintain healthy lives. Unfortunately, the inappropriate utilization of
      medications can be harmful to older adult patients. Inappropriate pharmacotherapy
      may lead to overusing medications and polypharmacy. Polypharmacy can contribute
      to a higher incidence of adverse effects, increase the risk of dangerous drug
      interactions, cause noncompliance with appropriate medication use, and
      significantly increase the cost of health care. The polypharmacy issue with
      geriatric patients has been described as an epidemic and this issue must be
      addressed. This review provides objective rules that may help prevent
      polypharmacy. Consideration of these rules when prescribing, dispensing, and
      caring for older adult patients will improve the overall pharmacotherapy regimens
      instituted by healthcare providers. 

PMID- 25772048
TI  - Abuse of medications that theoretically are without abuse potential.
AB  - The potential for abuse of medications that are controlled substances is well
      known. Abuse of certain noncontrolled prescription drugs and over-the-counter
      medications also may occur. To some degree, any medication that exerts
      psychoactive effects may be abused if taken in high enough doses or by means that
      result in high serum or cerebrospinal fluid levels. Many clinicians may be
      unaware of the potential for abuse of these medications. This review examines
      evidence of the possibility of abuse of several common medications that
      theoretically do not have abuse potential, including cough and cold preparations,
      antihistamines, anticholinergics, antipsychotics, antidepressants,
      anticonvulsants, skeletal muscle relaxants, and antiemetics. Means by which such
      medications may be abused and biochemical and physiological mechanisms fostering
      their abuse also are discussed. 

PMID- 25772049
TI  - Uveal melanoma in the first 4 decades of life.
AB  - OBJECTIVES: According to reports in the clinical literature, metastatic uveal
      melanoma in young adults has not been well studied. This article describes the
      clinical characteristics and natural history of patients who were diagnosed as
      having uveal melanoma in the first 4 decades of life. METHODS: This was a chart
      review of patients aged 40 years or younger who were treated for metastatic uveal
      melanoma. The eligibility criteria included an established diagnosis of primary
      uveal melanoma that was treated with localized plaque radiation therapy or
      enucleation, the presence of radiologically confirmed systemic tumor metastasis,
      and available therapy and follow-up information. Sixty-five patients met the
      eligibility criteria and were included in our study. RESULTS: The interval
      between the time of diagnosis of the primary tumor to the diagnosis of systemic
      metastasis and the median survival duration from diagnosis of the primary and
      metastatic disease were significantly longer than were those of patients with
      uveal melanoma patients overall. CONCLUSIONS: Patients with uveal melanoma who
      are diagnosed within the first 4 decades of life have a better prognosis than do
      patients with uveal melanoma overall; however, the prognosis of patients with
      metastatic uveal melanoma remains poor.

PMID- 25772050
TI  - Vitamin D deficiency in pediatric patients with cystic fibrosis: associated risk
      factors in the northern United States.
AB  - OBJECTIVES: Cystic fibrosis (CF) is associated with vitamin D deficiency, which
      can lead to adverse effects including recurrent pulmonary infections and
      osteoporosis. We longitudinally investigated calcifediol or 25-hydroxyvitamin D
      (25(OH)D) levels for our pediatric patients with CF based on the time of year as
      well as vitamin D supplementation dosing ranges for these patients at our CF
      center. METHODS: We retrospectively evaluated vitamin D deficiency in our
      pediatric CF center for 2 years (baseline and annually) while evaluating 25(OH)D
      serum changes based on vitamin D supplementation, seasonality, patient age, and
      other factors associated with CF. RESULTS: Vitamin D supplementation was noted to
      be higher than current Cystic Fibrosis Foundation dosing recommendations, and no
      patient experienced vitamin D toxicity. Seasonality was a strong indicator of
      25(OH)D levels, especially during summer or fall. Significantly fewer patients
      with initially low 25(OH)D levels maintained low levels at the conclusion of the
      study, suggesting benefit. Older patient age and higher supplemental dosing
      correlated with significantly lower 25(OH)D levels. CONCLUSIONS: This study
      suggests that targeted intervention among pediatric patients with CF living in
      northern latitudes of the United States, especially older children, is needed to
      prevent vitamin D deficiency.

PMID- 25772051
TI  - Trends in cigarette smoking and obesity in Appalachian Kentucky.
AB  - OBJECTIVES: The southern region of the United States, particularly central and
      southern Appalachia, has long been identified as an area of health inequities. An
      updated and more complete understanding of the association among the leading risk
      factors for such health inequities allows researchers, clinicians, and
      policymakers to focus their efforts on the most effective strategies to minimize
      these risks. METHODS: Using the most recent survey data from the Behavioral Risk
      Factor Surveillance System, we examined 10-year trends in rates of cigarette
      smoking and obesity in Appalachian Kentucky, comparing these trends with national
      and non-Appalachian Kentucky rates. RESULTS: Women and men from Appalachian
      Kentucky smoke cigarettes at rates 1.8 times and 1.6 times higher, respectively,
      than their national counterparts. Although rates of smoking in Appalachian
      Kentucky, non-Appalachian Kentucky, and the United States have decreased, such
      decreases among Appalachian Kentucky women have been minimal. Adding to these
      concerning trends, obesity rates in Appalachian adults are much higher than in
      non-Appalachian Kentucky or the United States overall, although Appalachian
      Kentucky smokers are less likely to be obese than nonsmokers. Low socioeconomic
      status and impeded access to health care characterize the Appalachian communities
      in which these risk behaviors occur and likely account for the prevalence of
      these most risky behaviors. CONCLUSIONS: A continuum of approaches to address
      smoking and obesity is warranted. Such approaches range from ensuring access to
      smoking cessation programs to implementing community- and state-level policies to
      curb smoking and unhealthy energy balance (eg, smoke-free policies and increases
      in tobacco and "junk food" taxes) and culturally appropriate individual-level
      interventions (evidence-based smoking cessation and weight-loss programming).

PMID- 25772052
TI  - Commentary on "trends in cigarette smoking obesity in Appalachian Kentucky".

PMID- 25772053
TI  - Rural-urban differences in HIV viral loads and progression to AIDS among new HIV
      cases.
AB  - OBJECTIVE: The human immunodeficiency virus/acquired immunodeficiency syndrome
      (HIV/AIDS) epidemic in the United States has shifted to the South, where an
      increasing proportion is occurring in rural areas. We sought to gain a better
      understanding of the affected rural population in this region. METHODS: The
      statewide HIV/AIDS Electronic Reporting System database was used to examine the
      epidemiological characteristics of newly diagnosed HIV cases in South Carolina
      from 2005 to 2011. Rural-urban differences were examined in sociodemographic and
      clinical characteristics, including progression to AIDS and a decline in HIV
      viral load (VL) to undetectable levels within 1 year of diagnosis. RESULTS: Of
      the 5336 individuals newly diagnosed as having HIV, 1433 (26.9%) were from rural
      areas. Compared with urban residents, a higher proportion of rural residents were
      black, non-Hispanic (80.1% vs 68.5%; P <= 0.0001) and reported heterosexual risk
      (28.8% vs 22.9%; P = 0.0007). The proportion of female patients was higher in
      rural areas (29.7% vs 26.4%; P = 0.016). No significant rural-urban differences
      were found in initial CD4(+) T-cell and VL counts or proportion obtaining an
      undetectable VL at 1 year. Rural residents were significantly more likely than
      urban residents to have AIDS at diagnosis or within 1 year of the HIV diagnosis
      (adjusted odds ratio 1.15; 95% confidence interval 1.007-1.326). CONCLUSIONS: The
      reasons behind differences in proportions of rural and urban residents who were
      diagnosed as having AIDS or progressed to AIDS despite similar initial CD4(+) T
      cell counts and VL suppression at 1 year are unclear and should be explored in
      future studies. Future prevention and treatment efforts may need to consider the
      unique characteristics of rural populations in the South.

PMID- 25772054
TI  - Religion, sense of calling, and the practice of medicine: findings from a
      national survey of primary care physicians and psychiatrists.
AB  - OBJECTIVES: A sense of calling is a concept with religious and theological roots;
      however, it is unclear whether contemporary physicians in the United States still
      embrace this concept in their practice of medicine. This study assesses the
      association between religious characteristics and endorsing a sense of calling
      among practicing primary care physicians (PCPs) and psychiatrists. METHODS: In
      2009, we surveyed a stratified random sample of 2016 PCPs and psychiatrists in
      the United States. Physicians were asked whether they agreed with the statement,
      "For me, the practice of medicine is a calling." Primary predictors included
      demographic and self-reported religious characteristics, (eg, attendance,
      affiliation, importance of religion, intrinsic religiosity) and spirituality.
      RESULTS: Among eligible respondents, the response rate was 63% (896/1427) for
      PCPs and 64% (312/487) for psychiatrists. A total of 40% of PCPs and 42% of
      psychiatrists endorsed a strong sense of calling. PCPs and psychiatrists who were
      more spiritual and/or religious as assessed by all four measures were more likely
      to report a strong sense of calling in the practice of medicine. Nearly half of
      Muslim (46%) and Catholic (45%) PCPs and the majority of evangelical Protestant
      PCPs (60%) report a strong sense of calling in their practice, and PCPs with
      these affiliations were more likely to endorse a strong sense of calling than
      those with no affiliation (26%, bivariate P < 0.001). We found similar trends for
      psychiatrists. CONCLUSIONS: In this national study of PCPs and psychiatrists, we
      found that PCPs who considered themselves religious were more likely to report a
      strong sense of calling in the practice of medicine. Although this cross
      sectional study cannot be used to make definitive causal inferences between
      religion and developing a strong sense of calling, PCPs who considered themselves
      religious are more likely to embrace the concept of calling in their practice of
      medicine.

PMID- 25772055
TI  - Commentary on "religion, sense of calling, and the practice of medicine: findings
      from a national survey of primary care physicians and psychiatrists".

PMID- 25772056
TI  - Time to dedifferentiate.

PMID- 25772057
TI  - Commentary on "time to dedifferentiate".

PMID- 25772059
TI  - Inhibition of clathrin-mediated endocytosis prevents amyloid beta-induced axonal
      damage.
AB  - Amyloid beta (Abeta)-induced axonal degeneration is a major cause of Alzheimer's
      disease (AD) pathology. However, the critical target to prevent Abeta-induced
      axonal degeneration remains unknown. Here, we analyzed growth cone collapse
      elicited by Abeta, a putative early Abeta-induced event in axons. Although no
      study has yet shown influence of Abeta on the growth cone, we first visualized
      Abeta-initiated growth cone collapse in cultured neurons. Furthermore, we
      determined that the collapse was triggered by clathrin-mediated endocytosis
      probably via Abeta-Ca(2+) signaling. The inhibition of clathrin-mediated
      endocytosis prevented Abeta-induced axonal loss both in vitro and in vivo and
      prevented memory impairment in an AD mouse model. Our results clarified the
      important role of clathrin-mediated endocytosis in Abeta-induced collapse of
      growth cone that leads to axonal degeneration and memory impairment. 

PMID- 25772060
TI  - Protection of injured retinal ganglion cell dendrites and unfolded protein
      response resolution after long-term dietary resveratrol.
AB  - Long-term dietary supplementation with resveratrol protects against
      cardiovascular disease, osteoporesis, and metabolic decline. This study
      determined how long-term dietary resveratrol treatment protects against retinal
      ganglion cell (RGC) dendrite loss after optic nerve injury and alters the
      resolution of the unfolded protein response. Associated changes in markers of
      endoplasmic reticulum stress in RGCs also were investigated. Young-adult Thy1
      yellow fluorescent protein (YFP) and C57BL/6 mice received either control diet or
      diet containing resveratrol for approximately 1 year. Both groups then received
      optic nerve crush (ONC). Fluorescent RGC dendrites in the Thy1-YFP mice were
      imaged weekly for 4 weeks after ONC. There was progressive loss of dendrite
      length in all RGC types within the mice that received control diet. Resveratrol
      delayed loss of dendrite complexity and complete dendrite loss for most RGC
      types. However, there were variations in the rate of retraction among different
      RGC types. Three weeks after ONC, cytoplasmic binding immunoglobulin protein
      (BiP) suppression observed in control diet ganglion cell layer neurons was
      reversed in mice that received resveratrol, nuclear C/EBP homologous protein
      (CHOP) was near baseline in control diet eyes but was moderately increased by
      resveratrol; and increased nuclear X-box-binding protein-1 (XBP-1) observed in
      control diet eyes was reduced in eyes that received resveratrol to the same level
      as in control diet uncrushed eyes. These results indicate that protection of
      dendrites by resveratrol after ONC differs among RGC types and suggest that
      alterations in long-term expression of binding immunoglobulin protein, CHOP, and
      XBP-1 may contribute to the resveratrol-mediated protection of RGC dendrites
      after ONC. 

PMID- 25772061
TI  - GPCR structure, function, drug discovery and crystallography: report from
      Academia-Industry International Conference (UK Royal Society) Chicheley Hall, 1-2
      September 2014.
AB  - G-protein coupled receptors (GPCRs) are the targets of over half of all
      prescribed drugs today. The UniProt database has records for about 800 proteins
      classified as GPCRs, but drugs have only been developed against 50 of these.
      Thus, there is huge potential in terms of the number of targets for new therapies
      to be designed. Several breakthroughs in GPCRs biased pharmacology, structural
      biology, modelling and scoring have resulted in a resurgence of interest in GPCRs
      as drug targets. Therefore, an international conference, sponsored by the Royal
      Society, with world-renowned researchers from industry and academia was recently
      held to discuss recent progress and highlight key areas of future research needed
      to accelerate GPCR drug discovery. Several key points emerged. Firstly,
      structures for all three major classes of GPCRs have now been solved and there is
      increasing coverage across the GPCR phylogenetic tree. This is likely to be
      substantially enhanced with data from x-ray free electron sources as they move
      beyond proof of concept. Secondly, the concept of biased signalling or functional
      selectivity is likely to be prevalent in many GPCRs, and this presents exciting
      new opportunities for selectivity and the control of side effects, especially
      when combined with increasing data regarding allosteric modulation. Thirdly,
      there will almost certainly be some GPCRs that will remain difficult targets
      because they exhibit complex ligand dependencies and have many metastable states
      rendering them difficult to resolve by crystallographic methods. Subtle effects
      within the packing of the transmembrane helices are likely to mask and contribute
      to this aspect, which may play a role in species dependent behaviour. This is
      particularly important because it has ramifications for how we interpret pre
      clinical data. In summary, collaborative efforts between industry and academia
      have delivered significant progress in terms of structure and understanding of
      GPCRs and will be essential for resolving problems associated with the more
      difficult targets in the future. 

PMID- 25772062
TI  - Enalapril stimulates collagen biosynthesis through prolidase-dependent mechanism
      in cultured fibroblasts.
AB  - The mechanism of a lower incidence of dermatological manifestations in patients
      treated with enalapril compared to patients treated with other ACE-inhibitors,
      e.g., captopril, is not known. The finding that prolidase plays an important role
      in collagen biosynthesis and that some angiotensin-converting enzyme inhibitors
      affect prolidase activity led us to evaluate its effect on collagen biosynthesis
      in cultured human skin fibroblasts. Since insulin-like growth factor (IGF-I) and
      transforming growth factor beta 1 (TGF-beta1) are the most potent stimulators of
      both collagen biosynthesis and prolidase activity, and prolidase is regulated by
      beta1 integrin signaling, the effect of enalapril and enalaprilat on IGF-IR, TGF
      beta1, and beta1 integrin receptor expressions was evaluated. Cells were treated
      with milimolar concentrations (0.3 and 0.5 mM) of enalapril and enalaprilat for
      24 h. The activity of prolidase was determined by colorimetic assay. Collagen
      biosynthesis was evaluated by radiometric assay. Expression of signaling proteins
      was evaluated using Western blot. It was found that enalapril- and enalaprilat
      dependent increase in prolidase activity and expression was accompanied by
      parallel increase in collagen biosynthesis. The exposure of the cells to 0.5 mM
      enalapril and enalaprilat contributed to increase in IGF-IR and alpha2beta1
      integrin receptor as well as TGF-beta1 and NF-kappaB p65 expressions. Enalapril-
      and enalaprilat-dependent increase of collagen biosynthesis in fibroblasts
      results from increase of prolidase activity and expression, which may undergo
      through activation of alpha2beta1 integrin and IGF-IR signaling as well as
      upregulation of TGF-beta1 and NF-kappaB p65, the inhibitor of collagen gene
      expression. 

PMID- 25772064
TI  - Susceptibility or vulnerability? The role of Basal cortisol in psychopathology.

PMID- 25772063
TI  - Organ-protective effects on the liver and kidney by minocycline in small piglets
      undergoing cardiopulonary bypass.
AB  - Cardiopulmonary bypass (CPB) often is required for the operative correction of
      congenital heart defects in small infants. Unfortunately, CPB is associated with
      injury of inner organs such as the brain, kidney, lung, and liver. Renal failure
      and increase in liver enzymes are typical side effects observed after CPB. Here,
      we investigate whether organ protection of the kidney and liver can be achieved
      with the application of minocycline, which is known-besides its anti-infective
      effects-to act as a poly-ADP-ribose-polymerase inhibitor. Twenty-nine 4-week-old
      Angler Sattelschwein-piglets (8-15 kg) were divided into four groups: control
      group (n = 8), CPB group (n = 9), minocycline-control group (n = 6), and the
      minocycline-CPB group (n = 6). CPB groups were thoracotomized and underwent CPB
      for 120 min (cross-clamp, 90 min; reperfusion, 30 min) followed by a 90-min
      recovery time. The control groups also were thoracotomized but not connected to
      CPB. The minocycline group received 4 mg/kg minocycline before and 2 mg/kg after
      CPB. In the kidneys, CPB histologically resulted in widening of Bowman's capsule,
      and-mainly in tubules-formation of poly-ADP-ribose, nitrosylation of tyrosine
      residues, nuclear translocation of hypoxia-induced factor HIF-1alpha, and of
      apoptosis-inducing factor (AIF). In addition, we found significantly less ATP in
      the kidney and significantly increased plasma urea and creatinine. Similar but
      gradually attenuated changes were found in the liver together with significantly
      elevated de-Ritis coefficient. These changes in the kidney and liver were
      significantly diminished by minocycline (except AIF in the liver which was
      similar in all groups). In conclusion, CPB causes damage in the kidney and-to a
      lower degree-in the liver, which can be attenuated by minocycline. 

PMID- 25772065
TI  - Modern screen-use behaviors: the effects of single- and multi-screen use on
      energy intake.
AB  - PURPOSE: The effects of using multiple screens at once on energy intake (EI) are
      unknown. This study compared EI of participants with access to multiple screens
      (television + iPad + smartphone) versus a single screen (television). METHODS: A
      laboratory-based, randomized, two-arm parallel (multi-screen vs. single-screen)
      trial was conducted in 78 adolescents (ages, 13-18 years). Food and drink were
      available during a 1-hour exposure period. Total EI was the primary outcome.
      Linear regression analyses were conducted to test the treatment difference,
      adjusting for age, sex, body mass index, and appetite at baseline. RESULTS: Total
      EI did not differ significantly between the two groups (multi-screen, 758 kcal
      [standard error = 75] vs. single-screen, 681 kcal [standard error = 75];
      difference, +77 kcal; 95% confidence interval, -166 to +320). CONCLUSIONS: EI did
      not differ between adolescents with access to multiple screens and those with
      access to a single screen; however, limitations in the study design may have
      decreased the power of the study.

PMID- 25772066
TI  - PtI2-catalyzed cyclization of 3-acyloxy-1,5-enynes with the elimination of HOAc
      and a benzyl shift: synthesis of unsymmetrical m-terphenyls.
AB  - A novel cyclization of 3-acyloxy-1,5-enynes is developed in the presence of PtI2
      for the synthesis of substituted unsymmetrical m-terphenyls in good to excellent
      yields. Two unique steps are involved in this transformation, which includes the
      elimination of HOAc and benzyl group migration. DFT calculations indicated that
      the rate-determining step is the migration of the benzylic carbocation to form a
      zwitterionic intermediate followed by the elimination of HOAc. The subsequent
      cyclopropanation of the zwitterionic intermediate is the regioselectivity
      determining step. 

PMID- 25772067
TI  - Hypertension in the Lebanese adults: impact on health related quality of life.
AB  - Cardiovascular disease is a major cause of morbidity and mortality worldwide,
      hypertension being one of their most prevalent risk factors. Information on
      health related quality of life (QOL) of hypertensive individuals in Lebanon is
      lacking. Our objectives were to evaluate QOL of hypertensive patients compared
      with non-hypertensive subjects and to suggest possible predictors of QOL in
      Lebanon. We conducted a case control study among individuals visiting outpatient
      clinics. Quality of life was assessed using the eight item (SF-8) questionnaire
      administered face to face to the study population, applied to hypertensive
      (N=224) and non-hypertensive control (N=448) groups. Hypertensive patients
      presented lower QOL scores in all domains, particularly in case of high
      administration frequency and occurrence of drug related side effects. Among
      hypertensive patients, QOL was significantly decreased with the presence of
      comorbidities (beta=-13.865, p=0.054), daily frequency of antihypertensive
      medications (beta=-8.196, p<0.001), presence of drug side-effects (beta=-19.262,
      p=0.031), older age (beta=-0.548, p<0.001), female gender (beta=-21.363, p=0.05),
      lower education (beta=-22.949, p=0.006), and cigarettes smoked daily (beta=
      0.726, p<0.001); regular sport activity (beta=23.15, p<0.001) significantly
      increased quality of life. These findings indicate the necessity for health
      professionals to take these factors into account when treating hypertensive
      patients, and to tackle special subgroups with attention to their deteriorated
      QOL. 

PMID- 25772068
TI  - Erythematotelangiectatic rosacea following occupational ultraviolet radiation
      injury.

PMID- 25772069
TI  - Lung transplantation with donation after circulatory determination of death
      donors and the impact of ex vivo lung perfusion.
AB  - The growing demand for suitable lungs for transplantation drives the quest for
      alternative strategies to expand the donor pool. The aim of this study is to
      evaluate the outcomes of lung transplantation (LTx) with donation after
      circulatory determination of death (DCDD) and the impact of selective ex vivo
      lung perfusion (EVLP). From 2007 to 2013, 673 LTx were performed, with 62 (9.2%)
      of them using DCDDs (seven bridged cases). Cases bridged with mechanical
      ventilation/extracorporeal life support were excluded. From 55 DCDDs, 28 (51%)
      underwent EVLP. Outcomes for LTx using DCDDs and donation after neurological
      determination of death (DNDD) donors were similar, with 1 and 5-year survivals of
      85% and 54% versus 86% and 62%, respectively (p = 0.43). Although comparison of
      survival curves between DCDD + EVLP versus DCDD-no EVLP showed no significant
      difference, DCDD + EVLP cases presented shorter hospital stay (median 18 vs. 23
      days, p = 0.047) and a trend toward shorter length of mechanical ventilation (2
      vs. 3 days, p = 0.059). DCDDs represent a valuable source of lungs for
      transplantation, providing similar results to DNDDs. EVLP seems an important
      technique in the armamentarium to safely increase lung utilization from DCDDs;
      however, further studies are necessary to better define the role of EVLP in this
      context. 

PMID- 25772070
TI  - miRNA plays a role in the antagonistic effect of selenium on arsenic stress in
      rice seedlings.
AB  - MicroRNAs (miRNAs), the small non-coding RNAs, have been implicated in various
      biological processes including adaptation during environmental stress. The
      present work explores the involvement of miRNA during arsenic (As) and selenium
      (Se) treatment in rice seedlings. Arsenic is a heavy metalloid causing severe
      adverse effects on the growth and development of plants while Se is another
      metalloid and an essential micro-nutrient when present in appropriate amounts. It
      was observed that the presence of Se along with As mitigated the adverse effects
      of As on seedling germination, root-shoot growth, total chlorophyll and protein
      contents. The measurement of stress indicators such as proline, cysteine and MDA
      also indicated similar effects. Analysis of the miRNA profile using microarrays
      under As, Se and As + Se treatments showed differential regulation of at least 46
      miRNAs in rice seedlings compared to untreated control. 18 of these miRNAs showed
      differential regulation among different treatments. Furthermore the microarray
      data were validated using real time PCR. The target genes of a few of these
      miRNAs showed inverse transcript accumulation. The possible role of miR395 and
      miR398 in the antagonistic effect on the adverse response of As in the presence
      of Se in rice seedlings is discussed. 

PMID- 25772071
TI  - Elucidating molecular phenotypes caused by the SORL1 Alzheimer's disease genetic
      risk factor using human induced pluripotent stem cells.
AB  - Predisposition to sporadic Alzheimer's disease (SAD) involves interactions
      between a person's unique combination of genetic variants and the environment.
      The molecular effect of these variants may be subtle and difficult to analyze
      with standard in vitro or in vivo models. Here we used hIPSCs to examine genetic
      variation in the SORL1 gene and possible contributions to SAD-related phenotypes
      in human neurons. We found that human neurons carrying SORL1 variants associated
      with an increased SAD risk show a reduced response to treatment with BDNF, at the
      level of both SORL1 expression and APP processing. shRNA knockdown of SORL1
      demonstrates that the differences in BDNF-induced APP processing between
      genotypes are dependent on SORL1 expression. We propose that the variation in
      SORL1 expression induction by BDNF is modulated by common genetic variants and
      can explain how genetic variation in this one locus can contribute to an
      individual's risk of developing SAD.

PMID- 25772072
TI  - Long non-coding RNAs control hematopoietic stem cell function.
AB  - Hematopoietic stem cells (HSCs) possess unique gene expression programs that
      enforce their identity and regulate lineage commitment. Long non-coding RNAs
      (lncRNAs) have emerged as important regulators of gene expression and cell fate
      decisions, although their functions in HSCs are unclear. Here we profiled the
      transcriptome of purified HSCs by deep sequencing and identified 323 unannotated
      lncRNAs. Comparing their expression in differentiated lineages revealed 159
      lncRNAs enriched in HSCs, some of which are likely HSC specific (LncHSCs). These
      lncRNA genes share epigenetic features with protein-coding genes, including
      regulated expression via DNA methylation, and knocking down two LncHSCs revealed
      distinct effects on HSC self-renewal and lineage commitment. We mapped the
      genomic binding sites of one of these candidates and found enrichment for key
      hematopoietic transcription factor binding sites, especially E2A. Together, these
      results demonstrate that lncRNAs play important roles in regulating HSCs,
      providing an additional layer to the genetic circuitry controlling HSC function.

PMID- 25772073
TI  - Lymphoid regeneration from gene-corrected SCID-X1 subject-derived iPSCs.
AB  - X-linked Severe Combined Immunodeficiency (SCID-X1) is a genetic disease that
      leaves newborns at high risk of serious infection and a predicted life span of
      less than 1 year in the absence of a matched bone marrow donor. The disease
      pathogenesis is due to mutations in the gene encoding the Interleukin-2 receptor
      gamma chain (IL-2Rgamma), leading to a lack of functional lymphocytes. With the
      leukemogenic concerns of viral gene therapy there is a need to explore
      alternative therapeutic options. We have utilized induced pluripotent stem cell
      (iPSC) technology and genome editing mediated by TALENs to generate isogenic
      subject-specific mutant and gene-corrected iPSC lines. While the subject-derived
      mutant iPSCs have the capacity to generate hematopoietic precursors and myeloid
      cells, only wild-type and gene-corrected iPSCs can additionally generate mature
      NK cells and T cell precursors expressing the correctly spliced IL-2Rgamma. This
      study highlights the potential for the development of autologous cell therapy for
      SCID-X1 subjects.

PMID- 25772074
TI  - A frameshift mutation in HTRA1 expands CARASIL syndrome and peripheral small
      arterial disease to the Chinese population.
AB  - Cerebral autosomal recessive arteriopathy with subcortical infarcts and
      leukoencephalopathy (CARASIL) is a rare hereditary cerebral artery disease. The
      HtrA serine protease 1 (HTRA1) gene has been identified as the causative gene of
      CARASIL. Here, we report a novel mutation in the HTRA1 gene in a CARASIL pedigree
      and explore its pathogenesis at the protein level. Subcutaneous tissue biopsy and
      HTRA1 gene analysis were performed in a CARASIL patient, and HTRA1 and TGF-beta1
      protein expression in subcutaneous tissue and cultured fibroblasts from the
      proband were detected by immunohistochemistry and western blotting. A 28-year-old
      male proband and his brother experienced recurrent stroke, hair loss and low back
      pain. Abnormalities in the proband were found in the elastic plate of
      subcutaneous small arteries, and a novel homozygous frameshift mutation
      (c.161_162insAG), leading to the formation of a stop codon 159 amino acids
      downstream of the insertion (p.Gly56Alafs*160) was detected. Reduced HTRA1
      protein and increased TGF-beta1 expression were detected in subcutaneous tissue
      and in cultured fibroblasts. A frameshift mutation in the HTRA1 gene detected in
      a CARASIL pedigree resulted in reduced HTRA1 protein and increased TGF-beta1
      expression, which may cause severe CARASIL and peripheral small arterial disease.

PMID- 25772075
TI  - A case report of bilateral paramedian thalamic and occult midbrain infarctions
      without disturbance of consciousness.

PMID- 25772076
TI  - Reversible splenial lesion and complex visual disturbances due to carbamazepine
      withdrawal.

PMID- 25772077
TI  - The role of uric acid as a potential neuroprotectant in acute ischemic stroke: a
      review of literature.
AB  - Uric acid (UA), a product of purine metabolism, is a kind of powerful endogenous
      antioxidant which may increase in many oxidative stress situations such as
      stroke. Some studies have found that UA is a predictor for stroke by mechanisms
      involved in development. There are some controversies about whether it is an
      independent effect of UA or an epiphenomenon. UA has been widely concerned for
      its neuroprotective effect as an antioxidant. In some experimental models of
      acute ischemic stroke, UA levels are associated with better functional recovery
      because of its synergistic effect with alteplase. In this review, a comprehensive
      literature search was conducted through Pubmed (1980-October 2014) to review the
      association of UA with the outcome of stroke. Finally, we outline the available
      clinical trial data supporting UA as a type of neuroprotective agents for the
      ischemic stroke.

PMID- 25772085
TI  - Standardized referral form: Restricting client-centered practice?
AB  - BACKGROUND: To increase homecare efficiency, the Ministry of Health and Social
      Services in Quebec, Canada, encourages standardization of practices, including
      those of community occupational therapists (COTs). The impact of standardization
      is not known and might reduce client-centeredness. Aim/objectives. To explore the
      content and use of a referral form to standardize COTs' practice.
      MATERIAL/METHODS: An institutional ethnography inquiry was conducted through
      observations of work and interviews with 10 COTs working in three homecare
      programs. Secondary informants were also interviewed and documents collected.
      Data were analyzed using institutional ethnography procedures. FINDINGS: The
      referral form, completed by the COTs' colleagues, includes categories primarily
      related to safety or autonomy in personal care and mobility. The form organizes
      COTs' work, including information collection and interactions with clients and
      caregivers. Seen as consultants, COTs assess needs and make recommendations to
      keep clients at home safely for as long as possible, an important element of the
      homecare discourse. CONCLUSION/SIGNIFICANCE: The impact on COTs' potential to be
      truly client-centered revealed by these findings merits serious consideration by
      other health professionals. Concerted efforts by professionals to question and
      act upon contextual barriers to client-centeredness are needed.

PMID- 25772086
TI  - Evaluation of a new tourniquet for hand surgery: Comparison of 76 carpal tunnel
      syndrome cases operated using a Hemaclear((r)) Model-F tourniquet versus a
      pneumatic tourniquet.
AB  - The aim of this study was to compare a forearm-specific, sterile, single-use, non
      pneumatic tourniquet to a conventional pneumatic tourniquet during carpal tunnel
      syndrome procedures. Patients with a systolic blood pressure exceeding 160 mmHg
      were excluded. The study included 76 patients. In 38 patients, surgery was
      performed with a pneumatic tourniquet on the forearm. In the remaining 38
      patients, surgery was performed with a Hemaclear((r)) Model-F tourniquet. There
      were no significant differences between the two groups in terms of quality of the
      exsanguination or pain experienced by the patient. The duration of surgery was
      significantly faster by 30 seconds with the Hemaclear((r)) tourniquet but the
      procedure cost was about ?30 more. The forearm-specific Hemaclear((r)) tourniquet
      has several theoretical advantages, but our clinical results do not support these
      advantages in terms of quality of the surgical exsanguination and pain
      experienced by the patient. The duration of surgery was significantly shorter,
      but at the price of a higher surgery cost.

PMID- 25772087
TI  - Visible light photooxidation of nitrate: the dawn of a nocturnal radical.
AB  - Highly oxidizing nitrate radicals (NO3) are easily accessed from readily
      available nitrate salts by visible light photoredox catalysis using a purely
      organic dye as the catalyst and oxygen as the terminal oxidant. The interaction
      of the excited catalyst and nitrate anions was studied by spectroscopic methods
      to elucidate the mechanism, and the method was applied to the NO3 induced
      oxidation of alkynes and alcohols. 

PMID- 25772088
TI  - Characterization of symptomatic lumbar foraminal stenosis by conventional
      imaging.
AB  - PURPOSE: The preoperative identification of lumbar foraminal stenosis (LSFS) is
      important because a lack of recognition of this clinical entity is often
      associated with failed back surgery syndrome. Although magnetic resonance imaging
      (MRI) is widely used, and is considered by many as an appropriate tool for
      studying spine pathologies, there is limited data to suggest that MRI
      examinations are sufficiently sensitive or specific for the diagnosis of LSFS.
      There is a paucity of literature on the diagnostic performance of the combination
      of conventional diagnostic imaging methods. The purpose of this study is to
      determine the characteristics of conventional diagnostic imaging for symptomatic
      lumbar foraminal stenosis. METHODS: The characteristics of conventional
      diagnostic imaging of LSFS (X-ray, computed tomography (CT) and MRI) were
      assessed in 68 patients in whom the site of the stenosis was confirmed by means
      of selective decompression surgeries. RESULTS: Measurement of the foraminal width
      and height on CT imaging of the diseased side was significantly less than that on
      the intact side in the LSFS group. The grading scale for facet joint arthritis on
      the diseased side was significantly higher than that on the intact side in the
      LSFS group. The prevalence of the vacuum phenomenon and stage of intervertebral
      disk (IVD) pathology were higher in the L5-S1 spine of the LSFS group (95.2%)
      compared with the lumbar spinal canal stenosis (LCS) group (21.1%). MRI study
      revealed that the prevalence of Type 3 Modic changes was significantly higher in
      the LSFS group (39.3%) compared with the LCS group (7.7%). CONCLUSIONS: Our study
      demonstrates combination of conventional imaging techniques, to improve the
      detection of symptomatic foraminal stenosis.

PMID- 25772089
TI  - Tokuhashi score is predictive of survival in a cohort of patients undergoing
      surgery for renal cell carcinoma spinal metastases.
AB  - PURPOSE: Renal cell carcinoma (RCC) is an aggressive disease that metastasizes to
      the spine often requiring surgery. However, selecting the appropriate surgical
      intervention can be challenging. The Tokuhashi scoring system can be used to
      predict survival and inform the surgical strategy. We set out to determine the
      Tokuhashi score for patients with RCC spine metastases and compare expected and
      observed survival. METHODS: Records were reviewed for all patients who underwent
      surgery for spinal metastases at a single institution from January 2000 to
      December 2011 to determine the Tokuhashi score and survival. Kaplan-Meier
      estimates and log-rank test for univariate analysis were performed with R version
      2.15.12 (R Foundation, 2012). RESULTS: Thirty patients underwent 40 spinal
      operations for metastatic RCC. Median survival was 11.4 months. Preoperative
      Tokuhashi scores were: 12-15, 15 patients; 9-11, seven patients; 0-8, eight
      patients. Median survival was 32.9, 11.7, and 5.4 months, respectively. Bone
      (p=0.01) and visceral metastases (p=0.005), and KPS (p=0.002) significantly
      affected survival. Tokuhashi score predicted survival (p=0.016); survival
      differed between the high and low score groups (p=0.006). CONCLUSIONS: RCC is an
      aggressive disease with short life expectancy when metastatic to the spine.
      However, patients with low systemic disease burden and solitary spinal metastases
      can have long survival and benefit from excisional surgery. Tokuhashi score can
      be useful in selecting surgical intervention in patients with RCC spinal
      metastases, and may be more relevant than in other cancers with spinal
      metastases.

PMID- 25772090
TI  - Catechol-O-methyltransferase (COMT) gene polymorphisms are associated with
      baseline disability but not long-term treatment outcome in patients with chronic
      low back pain.
AB  - PURPOSE: To examine the association between COMT and OPRM1 gene polymorphisms and
      pain and disability at baseline and long-term follow-up in patients treated for
      chronic low back pain (LBP). METHODS: 371 of 767 unrelated European patients
      recruited from four randomised trials underwent genetic analyses at mean 11.4
      years follow-up. 274 patients had fusion and 97 had non-operative treatment.
      Association analyses included disability, pain, five single nucleotide
      polymorphisms (SNPs) in the COMT gene, and one SNP in the OPRM1 gene. Analyses
      were adjusted for age, gender, smoking, analgesics and treatment. RESULTS:
      Disability at baseline was significantly associated with COMT SNPs rs4818 (p =
      0.02), rs6269 (p = 0.007), rs4633 (p = 0.04) rs2075507 (p = 0.009), two
      haplotypes (p < 0.002), age, gender and smoking (p <= 0.002). No significant
      associations with clinical variables were observed for OPRM1, or for COMT at long
      term follow-up. CONCLUSIONS: Results suggest that genetic factors are partly
      responsible for the variation in disability levels in patients presenting with
      chronic LBP being considered for surgery; in contrast, genetics has no influence
      on the long-term outcome of treatment.

PMID- 25772091
TI  - Letter to the Editor concerning "Video raster stereography back shape
      reconstruction: a reliability study for sagittal, frontal, and transversal plane
      parameters" by Schroeder J, Reer R, Braumann KM (2015) Eur Spine J 24(2):262-269.

PMID- 25772093
TI  - Finite element analysis of lordosis restoration with anterior longitudinal
      ligament release and lateral hyperlordotic cage placement.
AB  - PURPOSE: Restoring sagittal alignment is an important factor in the treatment of
      spinal deformities. Recent investigations have determined that releasing the
      anterior longitudinal ligament (ALL) and placing hyperlordotic cages can increase
      lordosis, while minimizing need for 3 column osteotomies. The influences of
      parameters such as cage height and angle have not been determined. Finite element
      analysis was employed to assess the extent of lordosis achievable after placement
      of different sized lordotic cages. METHODS: A 3-dimensional model of a L3-4
      segment was used. Disc distraction was simulated by inserting interbody cages mid
      body in the disc space. Analyses were performed in the following conditions: (1)
      intact, (2) ALL release, (3) ALL release + facetectomy, and (4) ALL release +
      posterior column osteotomy. Changes in segmental lordosis, disc height, foraminal
      height, and foraminal area were measured. RESULTS: After ALL resection and
      insertion of hyperlordotic cages, lordosis was increased in all cases. The
      lordosis achieved by the shorter cages was less due to posterior disc height
      maintained by the facet joints. A facetectomy increased segmental lordosis, but
      led to contact between the spinous processes. For some configurations, a
      posterior column osteotomy was required if the end goal was to match cage angle
      to intradiscal angle. CONCLUSION: Increased segmental lumbar lordosis is
      achievable with hyperlordotic cages after ALL resection. Increased cage height
      tended to increase the amount of lordosis achieved, although in some cases
      additional posterior bone resection was required to maximize lordosis. Further
      studies are needed to evaluate the impact on regional lumbar lordosis.

PMID- 25772092
TI  - Complications and cancer rates in spine fusion with recombinant human bone
      morphogenetic protein-2 (rhBMP-2).
AB  - PURPOSE: To quantitatively synthesize the available best evidence for general
      complications, heterotopic ossification (HO), retrograde ejaculation, cervical
      swelling, and cancer rates with the use of rhBMP-2 in lumbar and cervical spine
      fusion. METHODS: We conducted an online search for relevant controlled trials and
      extracted data on the abovementioned endpoints. Studies were eligible for
      inclusion if they reported on spinal fusion with rhBMP-2 in humans. Publication
      bias and heterogeneity were assessed mathematically. These data were synthesized
      in a meta-analysis using DerSimonian-Laird random effects modeling to calculate
      pooled odds ratios. RESULTS: We identified 26 studies reporting on a total of
      184,324 patients (28,815 experimental, 155,509 controls) with a mean age of 51.1
      +/- 1.8 years. There was a significantly higher risk of general complications
      with rhBMP-2 compared to iliac crest bone graft (ICBG) with an odds ratio (OR) of
      1.78 (95 %CI 1.20-2.63), (p = 0.004). The odds ratio for HO was 5.57 (95 %CI 1.90
      16.36), (p = 0.002), for retrograde ejaculation 3.31 (95 %CI 1.20-9.09), (p =
      0.020), and for cervical swelling 4.72 (95 %CI 1.42-15.67), (p = 0.011), all
      significantly higher in the rhBMP-2 group. The pooled odds ratio for new onset of
      tumor was 1.35 (95 %CI 0.93-1.96), which represents no statistically significant
      difference between the groups (p = 0.111). CONCLUSION: rhBMP-2 is associated with
      a higher rate of general complications as well as retrograde ejaculation, HO, and
      cervical tissue swelling in spine fusion. There is a slightly increased risk of
      new onset of tumors, however, without statistical significance.

PMID- 25772094
TI  - Pharmacokinetics of tulathromycin after subcutaneous injection in North American
      bison (Bison bison).
AB  - Tulathromycin is approved for the treatment of respiratory disease in cattle and
      swine. It is intended for long-acting, single-dose injection therapy (Draxxin),
      making it particularly desirable for use in bison due to the difficulty in
      handling and ease of creating stress in these animals. The pharmacokinetic
      properties of tulathromycin in bison were investigated. Ten wood bison received a
      single 2.5 mg/kg subcutaneous injection of Draxxin. Serum concentrations were
      measured by liquid chromatography-mass spectrometry (LC-MS) detection.
      Tulathromycin demonstrated early maximal serum concentrations, extensive
      distribution, and slow elimination characteristics. The mean maximum serum
      concentration (Cmax) was 195 ng/mL at 1.04 h (tmax) postinjection. The mean area
      under the serum concentration-time curve, extrapolated to infinity (AUC0-inf ),
      was 9341 ng . h/mL. The mean apparent volume of distribution (Vd /F) and
      clearance (Cls/F) was 111 L/kg and 0.4 L/h/kg, respectively, and the mean half
      life (t1/2) was 214 h (8.9 days). Compared to values for cattle, Cmax and AUC0
      inf were lower in bison, while the Vd /F was larger and the t1/2 longer. Tissue
      distribution and clinical efficacy studies in bison are needed to confirm the
      purported extensive distribution of tulathromycin into lung tissue and to
      determine whether a 2.5 mg/kg subcutaneous dosage is adequate for bison.

PMID- 25772095
TI  - Characterization of a tyramine receptor type 2 from hemocytes of rice stem borer,
      Chilo suppressalis.
AB  - Calcium acts as a second messenger in many cell types, including insect
      hemocytes. Intracellular calcium level has a definite role in innate and adaptive
      immune signaling. Biogenic amines such as octopamine (OA), tyramine (TA),
      dopamine (DA) and serotonin (5-HT) play various important physiological roles in
      insects by activating distinct G-protein-coupled receptors (GPCRs) that share a
      putative seven transmembrane domain structure. OA and 5-HT have been shown that
      can mediate insect hemocytic immune reactions to infections and invasions. Here,
      we showed that TA increase hemocyte spreading in the rice stem borer, Chilo
      suppressalis. Furthermore, we cloned a cDNA encoding a tyramine receptor type 2
      from the hemocytes in the C. suppressalis, viz., CsTA2, which shares high
      sequence similarity to members of the invertebrate tyramine receptor family. The
      CsTA2 receptor was stably expressed in human embryonic kidney (HEK) 293 cells,
      and its ligand response has been examined. Receptor activation with TA induced a
      dose-dependent increase in intracellular Ca(2+) concentration ([Ca(2+)]i) in
      cells, with an EC50 value of 18.7+/-5.3 nM, whereas OA, DA, 5-HT and other
      potential agonists did not have this response. The mRNA is present in various
      tissues including nerve cord, hemocytes, fat body, midgut, Malpighian tubules,
      and epidermis in the larval stage. Western blot analysis and immunohistochemistry
      assay displayed that CsTA2 was detected and presented on hemocytes. We also
      showed that TA induced Ca(2+) release from the hemocytes of C. suppressalis.

PMID- 25772096
TI  - Pupal X-ray irradiation influences protein expression in adults of the oriental
      fruit fly, Bactrocera dorsalis.
AB  - The oriental fruit fly, Bactrocera dorsalis, is a pest of fruit in the Asia
      Pacific region and also, due to quarantine restrictions, a threat to California
      fruit production. Area-wide suppression of B. dorsalis integrated several
      approaches including the sterile insect technique (SIT). SIT involves exposing
      juveniles to gamma radiation and releasing sterile males in substantial numbers,
      where they successfully compete for wild females. The resulting infertile eggs
      lead to reduction of the pest populations. Although these protocols are well
      documented, arising issues about the international transport and distribution of
      radioactive products is creating difficulties in use of radioactive sources for
      sterilizing radiation. This led to a shift toward use of X-ray irradiation, which
      also sterilizes male and female insects. However, use of X-ray technologies is in
      its infancy and there is virtually no information on the effects of irradiation,
      other than sterilization, at the physiological and molecular levels of fruit fly
      biology. We posed the hypothesis that sterilizing male oriental fruit flies via
      radiation treatment also influences protein expression in the flies. We found
      that exposing pupae to X-ray irradiation impacted expression of 26 proteins in
      adult females and 31 proteins in adult males. Seven proteins (glyceraldehyde-3
      phosphate dehydrogenase, fructose-bisphosphate aldolase, larval cuticle protein
      2, sarcoplasmic calcium-binding protein alpha-B and A chains, general odorant
      binding protein 99b, polyubiquitin, and protein disulfide-isomerase) were
      impacted in both sexes. Some of the proteins act in central energy-generating and
      in pheromone-signal processing pathways; we infer that males sterilized by X-ray
      irradiation may be enfeebled in their ability to compete with wild males for
      females in nature. 

PMID- 25772097
TI  - Mosaic dominant TUBB4A mutation in an inbred family with complicated hereditary
      spastic paraplegia.
AB  - BACKGROUND: Mutations in TUBB4A have been associated with a spectrum of
      neurological conditions, ranging from the severe hypomyelination with atrophy of
      the basal ganglia and cerebellum syndrome to the clinically milder dystonia type
      4. The presence of movement abnormalities was considered the common hallmark of
      these disorders. METHODS: Clinical, neurological, and neuroimaging examinations,
      followed by whole exome sequencing and mutation analysis, were performed in a
      highly consanguineous pedigree with five affected children. RESULTS: We
      identified a novel c.568C>T (p.H190Y) TUBB4A mutation that originated de novo in
      the asymptomatic mother. The affected subjects presented with an early-onset,
      slowly progressive spastic paraparesis of the lower limbs, ataxia, and brain
      hypomyelination, in the absence of dystonia or rigidity. CONCLUSIONS: Our study
      adds complicated hereditary spastic paraplegia to the clinical spectrum of TUBB4A
      associated neurological disorders. We establish genotype-phenotype correlations
      with mutations located in the same region in the tertiary structure of the
      protein.

PMID- 25772098
TI  - Retinotopy of visual masking and non-retinotopic perception during masking.
AB  - Due to the movements of the observer and those of objects in the environment,
      retinotopic representations are highly unstable during ecological viewing
      conditions. The phenomenal stability of our perception suggests that retinotopic
      representations are transformed into non-retinotopic representations. It remains
      to show, however, which visual processes operate under retinotopic
      representations and which ones operate under non-retinotopic representations.
      Visual masking refers to the reduced visibility of one stimulus, called the
      target, due to the presence of a second stimulus, called the mask. Masking has
      been used extensively to study the dynamic aspects of visual perception. Previous
      studies using Saccadic Stimulus Presentation Paradigm (SSPP) suggested both
      retinotopic and non-retinotopic bases for visual masking. In order to understand
      how the visual system deals with retinotopic changes induced by moving targets,
      we investigated the retinotopy of visual masking and the fate of masked targets
      under conditions that do not involve eye movements. We have developed a series of
      experiments based on a radial Ternus-Pikler display. In this paradigm, the
      perceived Ternus-Pikler motion is used as a non-retinotopic reference frame to
      pit retinotopic against non-retinotopic visual masking hypothesis. Our results
      indicate that both metacontrast and structure masking are retinotopic. We also
      show that, under conditions that allow observers to read-out effectively non
      retinotopic feature attribution, the target becomes visible at a destination
      different from its retinotopic/spatiotopic location. We discuss the implications
      of our findings within the context of ecological vision and dynamic form
      perception.

PMID- 25772099
TI  - Attention and positive affect: temporal switching or spatial broadening?
AB  - Evolutionary reasoning and computation suggest that positive affect is associated
      with higher attentional flexibility than negative affect, even when affectively
      neutral material is processed. The affective modulation of interference in the
      Eriksen flanker task seems, however, more readily explained by a spatial
      broadening of attention due to positive affect. It is argued here that these
      results should also be interpreted in terms of an increased switching over time
      between flankers and target (i.e., flexibility). The two hypotheses were
      contrasted with positive and negative mood inductions in a masked-flanker task.
      The interval (Stimulus Onset Asynchrony; SOA) with which the masked flankers
      preceded the target letter was parametrically varied. In contrast to what is
      found with simultaneous non-masked flanker presentation, masking produced larger
      interference with negative than with positive moods. In addition, a crossover
      interaction between mood and SOA emerged. These results seem incompatible with a
      spatial broadening account and support an affective modulation account in terms
      of flexibility. 

PMID- 25772100
TI  - Rapid scene perception with tragic consequences: observers miss perceiving
      vulnerable road users, especially in crowded traffic scenes.
AB  - How does scene complexity influence the detection of expected and appropriate
      objects within the scene? Traffic research has indicated that vulnerable road
      users (VRUs: pedestrians, bicyclists, and motorcyclists) are sometimes not
      perceived, despite being expected. Models of scene perception emphasize
      competition for limited neural resources in early perception, predicting that an
      object can be missed during quick glances because other objects win the
      competition to be individuated and consciously perceived. We used pictures of
      traffic scenes and manipulated complexity by inserting or removing vehicles near
      a to-be-detected VRU (crowding). The observers' sole task was to detect a VRU in
      the laterally presented pictures. Strong bias effects occurred, especially when
      the VRU was crowded by other nearby vehicles: Observers failed to detect the VRU
      (high miss rates), while making relatively few false alarm errors. Miss rates
      were as high as 65% for pedestrians. The results indicated that scene context can
      interfere with the perception of expected objects when scene complexity is high.
      Because urbanization has greatly increased scene complexity, these results have
      important implications for public safety.

PMID- 25772101
TI  - Stored color-form knowledge modulates perceptual sensitivity in search.
AB  - We used signal detection analysis to examine the effects of stored color-form
      knowledge on visual search. Across four experiments, we showed robust effects of
      stored color-form knowledge on perceptual sensitivity, whereas the effects on
      response criteria varied. The effects on perceptual sensitivity were stronger
      when multiple items were present and when the color fell on the surface of the
      object. The benefit was found even when the correctly colored target had a low
      probability of occurrence in the experiment. In addition, the benefit was present
      across different display sizes, and the effects of increasing the exposure
      duration on detecting correctly colored targets were equal across different sizes
      of the display. The data suggest that color-form conjunctions are detected
      efficiently to activate stored color-form knowledge, and that this knowledge then
      influences early perceptual processing in a bottom-up manner. We discuss the
      implications for understanding the coding of conjunctive relations. 

PMID- 25772103
TI  - Multiple concurrent temporal recalibrations driven by audiovisual stimuli with
      apparent physical differences.
AB  - Out-of-synchrony experiences can easily recalibrate one's subjective simultaneity
      point in the direction of the experienced asynchrony. Although temporal
      adjustment of multiple audiovisual stimuli has been recently demonstrated to be
      spatially specific, perceptual grouping processes that organize separate
      audiovisual stimuli into distinctive "objects" may play a more important role in
      forming the basis for subsequent multiple temporal recalibrations. We
      investigated whether apparent physical differences between audiovisual pairs that
      make them distinct from each other can independently drive multiple concurrent
      temporal recalibrations regardless of spatial overlap. Experiment 1 verified that
      reducing the physical difference between two audiovisual pairs diminishes the
      multiple temporal recalibrations by exposing observers to two utterances with
      opposing temporal relationships spoken by one single speaker rather than two
      distinct speakers at the same location. Experiment 2 found that increasing the
      physical difference between two stimuli pairs can promote multiple temporal
      recalibrations by complicating their non-temporal dimensions (e.g., disks
      composed of two rather than one attribute and tones generated by multiplying two
      frequencies); however, these recalibration aftereffects were subtle. Experiment 3
      further revealed that making the two audiovisual pairs differ in temporal
      structures (one transient and one gradual) was sufficient to drive concurrent
      temporal recalibration. These results confirm that the more audiovisual pairs
      physically differ, especially in temporal profile, the more likely multiple
      temporal perception adjustments will be content-constrained regardless of spatial
      overlap. These results indicate that multiple temporal recalibrations are based
      secondarily on the outcome of perceptual grouping processes.

PMID- 25772102
TI  - Interdependent processing and encoding of speech and concurrent background noise.
AB  - Speech processing can often take place in adverse listening conditions that
      involve the mixing of speech and background noise. In this study, we investigated
      processing dependencies between background noise and indexical speech features,
      using a speeded classification paradigm (Garner, 1974; Exp. 1), and whether
      background noise is encoded and represented in memory for spoken words in a
      continuous recognition memory paradigm (Exp. 2). Whether or not the noise
      spectrally overlapped with the speech signal was also manipulated. The results of
      Experiment 1 indicated that background noise and indexical features of speech
      (gender, talker identity) cannot be completely segregated during processing, even
      when the two auditory streams are spectrally nonoverlapping. Perceptual
      interference was asymmetric, whereby irrelevant indexical feature variation in
      the speech signal slowed noise classification to a greater extent than irrelevant
      noise variation slowed speech classification. This asymmetry may stem from the
      fact that speech features have greater functional relevance to listeners, and are
      thus more difficult to selectively ignore than background noise. Experiment 2
      revealed that a recognition cost for words embedded in different types of
      background noise on the first and second occurrences only emerged when the noise
      and the speech signal were spectrally overlapping. Together, these data suggest
      integral processing of speech and background noise, modulated by the level of
      processing and the spectral separation of the speech and noise. 

PMID- 25772104
TI  - Genomic and post-genomic effects of anti-glaucoma drugs preservatives in
      trabecular meshwork.
AB  - Oxidative stress plays an important role in glaucoma. Some preservatives of anti
      glaucoma drugs, commonly used in glaucoma therapy, can prevent or induce
      oxidative stress in the trabecular meshwork. The aim of this study is to evaluate
      cellular and molecular damage induced in trabecular meshwork by preservatives
      contained in anti-glaucoma drugs. Cell viability (MTT test), DNA fragmentation
      (Comet test), oxidative DNA damage (8-oxo-dG), and gene expression (cDNA
      microarray) have been evaluated in trabecular meshwork specimens and in human
      trabecular meshwork cells treated with benzalkonium chloride, polyQuad, purite,
      and sofzia-like mixture. Moreover, antimicrobial effectiveness and safety of
      preservative contents in drugs was tested. In ex vivo experiments, benzalkonium
      chloride and polyQuad induced high level of DNA damage in trabecular meshwork
      specimens, while the effect of purite and sofzia were more attenuated. The level
      of DNA fragmentation induced by benzalkonium chloride was 2.4-fold higher in
      subjects older than 50 years than in younger subjects. Benzalkonium chloride, and
      polyQuad significantly increased oxidative DNA damage as compared to sham-treated
      specimens. Gene expression was altered by benzalkonium chloride, polyQuad, and
      purite but not by sofzia. In in vitro experiments, benzalkonium chloride and
      polyQuad dramatically decreased trabecular meshwork cell viability, increased DNA
      fragmentation, and altered gene expression. A lesser effect was also exerted by
      purite and sofzia. Genes targeted by these alterations included Fas and effector
      caspase-3. The efficacy of the preservatives in inhibiting bacterial growth
      increased the adverse effects in trabecular meshwork in terms of DNA damage and
      alteration of gene expression. Presented data indicates the delicate balance
      between efficacy and safety of drug preservatives as not yet optimized. 

PMID- 25772105
TI  - Further acatalasemia mutations in human patients from Hungary with diabetes and
      microcytic anemia.
AB  - In blood, the hydrogen peroxide concentration is regulated by catalase. Decreased
      activity of catalase may lead to increased hydrogen peroxide concentration, which
      may contribute to the manifestation of age-related disease. The aim of this study
      is to examine association of decreased blood catalase activity and catalase exon
      mutations in patients (n=617) with diabetes (n=380), microcytic anemia (n=58),
      beta-thalassemia (n=43) and presbycusis (n=136) and in controls (n=295). Overall,
      51 patients (8.3%) had less than half of normal blood catalase activity. Their
      genomic DNA was used for mutation screening of all exons and exon/intron
      boundaries with polymerase chain reaction-single-strand conformation polymorphism
      (PCR-SSCP) and PCR-heteroduplex analyses, and mutations were verified with
      nucleotide sequencing. Seven patients (type 2 diabetes (n=3), gestational
      diabetes (n=1), microcytic anemia (n=2)) had four novel catalase exon mutations
      namely, c.106_107insC, p.G36Afs*5(n=3, Hungarian type G1), c.379C>T, p.R127Y
      (n=2, Hungarian type H1), c.390T>C, p.R129L, (n=1, Hungarian type H2) and
      c.431A>T, p.N143V (n=1, Hungarian type H3). In patients with decreased blood
      catalase, the incidence of acatalasemia mutations was significantly high
      (P<0.0002) in microcytic anemia, type 2 and gestational diabetes. The four novel
      mutations were probably responsible for low blood catalase activity in 7/51
      patients. In the remainder of the cases, other polymorphisms and
      epigenetic/regulatory factors may be involved. 

PMID- 25772106
TI  - Association of polymorphisms in long non-coding RNA H19 with coronary artery
      disease risk in a Chinese population.
AB  - H19 is an imprinted gene transcribing a long non-coding RNA and is downregulated
      postnatally. Re-expression of H19 has been observed in patients with
      atherosclerosis. However, to date, no data has been published on the association
      of H19 polymorphisms with the risk of coronary artery disease (CAD). In this
      study, four polymorphisms, rs217727, rs2067051, rs2251375, rs4929984, were
      analyzed in 701 CAD patients and 873 age- and sex-matched control subjects.
      Polymorphisms were genotyped by TaqMan technology. Our data showed that the T
      variant of rs217727 was associated with an increased risk of CAD [additive model:
      odds ratio (OR)=2.05, 95%CI=1.35-3.12; dominant model: OR=1.46, 95% confidence
      interval (CI)=1.12-1.90; recessive model: OR=1.75, 95%CI=1.18-2.58], while A
      variant of rs2067051 was associated with a decreased risk of CAD (additive model:
      OR=0.66, 95%CI=0.45-0.96; recessive model: OR=0.71, 95%CI=0.50-0.99). Combined
      analysis showed that subjects carrying 3 or 4 risk alleles had a significantly
      increased risk of CAD, relative to those with 0-2 risk alleles (OR=1.61,
      95%CI=1.20-2.15). Moreover, CAD patients with 3 or 4 risk alleles also had
      significantly higher Gensini scores than those with 0-2 risk alleles (P=0.001).
      Further haplotype-based analysis revealed that individuals with C-G-C-C, T-G-A-A,
      and T-A-A-A haplotypes indicated a higher prevalence of CAD (OR=1.88, 95%CI=1.03
      3.43; OR=2.26, 95%CI=1.19-4.31; OR=2.66, 95%CI=1.34-5.25, respectively), compared
      to individuals with the most common C-G-A-C haplotype. In conclusion, our study
      demonstrates for the first time that common polymorphisms of H19 are associated
      with the risk and severity of CAD in a Chinese population. Future studies are
      needed to explore the underlying mechanisms of our findings. 

PMID- 25772107
TI  - SirT1 knockdown potentiates radiation-induced bystander effect through promoting
      c-Myc activity and thus facilitating ROS accumulation.
AB  - Radiation-induced bystander effect (RIBE) has important implications for
      secondary cancer risk assessment during cancer radiotherapy, but the bystander
      signaling processes, especially under hypoxic condition, are still largely
      unclear. The present study found that micronuclei (MN) formation could be induced
      in the non-irradiated HL-7702 hepatocyte cells after being treated with the
      conditioned medium from irradiated hepatoma HepG2 and SK-Hep-1 cells under either
      normoxia or hypoxia. This bystander response was dramatically diminished or
      enhanced when the SirT1 gene of irradiated hepatoma cells was overexpressed or
      knocked down, respectively, especially under hypoxia. Meanwhile, SirT1 knockdown
      promoted transcriptional activity for c-Myc and facilitated ROS accumulation. But
      both of the increased bystander responses and ROS generation due to SirT1
      knockdown were almost completely suppressed by c-Myc interference. Moreover, ROS
      scavenger effectively abolished the RIBE triggered by irradiated hepatoma cells
      even with SirT1 depletion. These findings provide new insights that SirT1 has a
      profound role in regulating RIBE where a c-Myc-dependent release of ROS may be
      involved. 

PMID- 25772108
TI  - Anxious phenotypes plus environmental stressors are related to brain DNA damage
      and changes in NMDA receptor subunits and glutamate uptake.
AB  - This study aimed at investigating the effects of chronic mild stress on DNA
      damage, NMDA receptor subunits and glutamate transport levels in the brains of
      rats with an anxious phenotype, which were selected to represent both the high
      freezing (CHF) and low-freezing (CLF) lines. The anxious phenotype induced DNA
      damage in the hippocampus, amygdala and nucleus accumbens (NAc). CHF rats
      subjected to chronic stress presented a more pronounced DNA damage in the
      hippocampus and NAc. NMDAR1 were increased in the prefrontal cortex (PC),
      hippocampus and amygdala of CHF, and decreased in the hippocampus, amygdala and
      NAc of CHF stressed. NMDAR2A were decreased in the amygdala of the CHF and
      stressed; and increased in CHF stressed. NMDRA2A in the NAc was increased after
      stress, and decreased in the CLF. NMDAR2B were increased in the hippocampus of
      CLF and CHF. In the amygdala, there was a decrease in the NMDAR2B for stress in
      the CLF and CHF. NMDAR2B in the NAc were decreased for stress and increased in
      the CHF; in the PC NMDAR2B increased in the CHF. EAAT1 increased in the PC of
      CLF+stress. In the hippocampus, EAAT1 decreased in all groups. In the amygdala,
      EAAT1 decreased in the CLF+stress and CHF. EAAT2 were decreased in the PC for
      stress, and increased in CHF+control. In the hippocampus, the EAAT2 were
      increased for the CLF and decreased in the CLF+stress. In the amygdala, there was
      a decrease in the EATT2 in the CLF+stress and CHF. These findings suggest that an
      anxious phenotype plus stress may induce a more pronounced DNA damage, and
      promote more alterations in the glutamatergic system. These findings may help to
      explain, at least in part, the common point of the mechanisms involved with the
      pathophysiology of depression and anxiety. 

PMID- 25772109
TI  - The non-targeted effects of radiation are perpetuated by exosomes.
AB  - Exosomes contain cargo material from endosomes, cytosol, plasma membrane and
      microRNA molecules, they are released by a number of non-cancer and cancer cells
      into both the extracellular microenvironment and body fluids such as blood
      plasma. Recently we demonstrated radiation-induced non-targeted effects [NTE:
      genomic instability (GI) and bystander effects (BE)] are partially mediated by
      exosomes, particularly the RNA content. However the mechanistic role of exosomes
      in NTE is yet to be fully understood. The present study used MCF7 cells to
      characterise the longevity of exosome-induced activity in the progeny of
      irradiated and unirradiated bystander cells. Exosomes extracted from conditioned
      media of irradiated and bystander progeny were added to unirradiated cells.
      Analysis was carried out at 1 and 20/24 population doublings following
      medium/exosome transfer for DNA/chromosomal damage. Results confirmed exosomes
      play a significant role in mediating NTE of ionising radiation (IR). This effect
      was remarkably persistent, observed >20 doublings post-irradiation in the progeny
      of bystander cells. Additionally, cell progeny undergoing a BE were themselves
      capable of inducing BE in other cells via exosomes they released. Furthermore we
      investigated the role of exosome cargo. Culture media from cells exposed to 2 Gy
      X-rays was subjected to ultracentrifugation and four inoculants prepared, (a)
      supernatants with exosomes removed, and pellets with (b) exosome proteins
      denatured, (c) RNA degraded, and (d) a combination of protein-RNA inactivation.
      These were added to separate populations of unirradiated cells. The BE was
      partially inhibited when either exosome protein or exosome RNA were inactivated
      separately, whilst combined RNA-protein inhibition significantly reduced or
      eliminated the BE. These results demonstrate that exosomes are associated with
      long-lived signalling of the NTE of IR. Both RNA and protein molecules of
      exosomes work in a synergistic manner to initiate NTE, spread these effects to
      naive cells, and perpetuate GI in the affected cells.

PMID- 25772110
TI  - Caenorhabditis elegans EXO-3 contributes to longevity and reproduction:
      differential roles in somatic cells and germ cells.
AB  - Apurinic/apyrimidinic (AP) sites are the major DNA damage generated continuously
      even under normal conditions, and inhibit DNA replication/transcription. AP
      endonucleases are ubiquitous enzymes required for the repair of AP sites and 3'
      blocking ends, but their physiological roles in multicellular organisms are not
      fully understood. In this study, we investigated how an AP endonuclease functions
      in a multicellular organism (Caenorhabditis elegans (C. elegans)). EXO-3 is one
      of the AP endonucleases in C. elegans. Using an exo-3 mutant worm, we found that
      deletion of the exo-3 gene caused shortened lifespan in an ung-1-dependent
      manner. UNG-1 is a uracil DNA glycosylase in C. elegans, and the present finding
      suggested that UNG-1 is the major producer of AP sites that affects lifespan, and
      EXO-3 contributes to longevity by completing the repair of uracil. Next we found
      that the exo-3 gene was abundantly expressed in the gonads, and AP sites in the
      gonad were efficiently repaired, suggesting that EXO-3 functioned particularly in
      the gonad. Deletion of the exo-3 gene resulted in a significant decrease in self
      brood size. This was rescued by deficiency of NTH-1, which is a bifunctional DNA
      glycosylase in C. elegans that recognizes oxidative base damage. This result
      suggested that the major substrate of EXO-3 in the gonad was 3' blocking end
      generated by NTH-1, and that EXO-3 played an important role in reproduction. A
      contribution of EXO-3 to reproduction was also suggested by our finding here that
      the decrease of self-brood size of the exo-3 mutant became more marked when worms
      were treated with methyl methanesulfonate (MMS) and sodium bisulfite (NaHSO3).
      This study demonstrated differential roles of EXO-3 in somatic cells and germ
      cells. 

PMID- 25772111
TI  - Editorial.

PMID- 25772113
TI  - Combined Vagal Stimulation and Limb Remote Ischemic Perconditioning Enhances
      Cardioprotection via an Anti-inflammatory Pathway.
AB  - Various combined interventions to acquire enhanced cardioprotection are prevalent
      focuses of current research. This randomized experiment assessed whether combined
      vagal stimulation perconditioning (VSPerC) and limb remote ischemic
      perconditioning (LRIPerC) improved cardioprotection compared to the use of either
      treatment alone in an in vivo rat model of myocardial ischemia/reperfusion
      injury. A total of 100 male Sprague Dawley rats were randomly allocated into five
      groups: sham group, ischemia/reperfusion (IR) group, VSPerC group, LRIPerC group,
      and combined VSPerC and LRIPerC (COMPerC) group. Serum enzymatic markers,
      inflammatory cytokines, myocardial inflammatory cytokines, and infarct size were
      assessed. Infarct size decreased significantly in the COMPerC group compared to
      the VSPerC and LRIPerC groups. Serum intercellular adhesion molecule 1 (ICAM-1)
      level at 120 min of reperfusion, myocardial interleukin-1 (IL-1), ICAM-1, and
      tumor necrosis factor alpha (TNF-alpha) levels in the ischemic region decreased
      significantly in the COMPerC group compared to the VSPerC group, but myocardial
      IL-10 levels in the nonischemic region increased markedly in the COMPerC group.
      Serum TNF-alpha levels at 30, 60, and 120 min of reperfusion; serum IL-1, IL-6,
      ICAM-1, and high mobility group box-1 protein (HMGB-1) levels at 120 min of
      reperfusion; and myocardial IL-1, IL-6, ICAM-1, and TNF-alpha levels in the
      ischemic region decreased significantly in the COMPerC group compared to the
      LRIPerC group. However, myocardial IL-10 levels in both ischemic and nonischemic
      regions were evidently higher in the COMPerC group. This study concludes that
      combined VSPerC and LRIPerC enhances cardioprotection compared to either
      treatment alone. This result is likely attributable to a more potent regulation
      of inflammation. 

PMID- 25772114
TI  - Alpha-Tomatine Exhibits Anti-inflammatory Activity in Lipopolysaccharide
      Activated Macrophages.
AB  - Alpha (alpha)-tomatine is the major saponin and occurs naturally in tomatoes,
      which has been confirmed to possess a variety of biological properties including
      antitumoral, antioxidant, and anti-inflammatory. However, the anti-inflammatory
      mechanism of alpha-tomatine is not well understood. This study aims to
      investigate the anti-inflammatory effects and mechanisms of alpha-tomatine.
      Results showed that alpha-tomatine significantly suppressed the production of pro
      inflammatory cytokines in lipopolysaccharide (LPS)-induced macrophages. Moreover,
      LPS-mediated nuclear translocation of the nuclear factor-kappaB (NF-kappaB)-p65
      and phosphorylation of extracellular signal-regulated kinase (ERK) 1/2 were
      attenuated after alpha-tomatine treatment. Still, LPS slightly promoted
      phosphorylation of Akt, and alpha-tomatine accelerated the phosphorylation of Akt
      in macrophages. Our findings indicate that alpha-tomatine may be a valuable
      therapeutic agent in the treatment of inflammation-related diseases. 

PMID- 25772112
TI  - Viscoelasticity and Ultrastructure in Coagulation and Inflammation: Two Diverse
      Techniques, One Conclusion.
AB  - The process of blood clotting has been studied for centuries. A synopsis of
      current knowledge pertaining to haemostasis and the blood components, including
      platelets and fibrin networks which are closely involved in coagulation, are
      discussed. Special emphasis is placed on tissue factor (TF), calcium and thrombin
      since these components have been implicated in both the coagulation process and
      inflammation. Analysis of platelets and fibrin morphology indicate that calcium,
      tissue factor and thrombin at concentrations used during viscoelastic analysis
      (with thromboelastography or TEG) bring about alterations in platelet and fibrin
      network ultrastructure, which is similar to that seen in inflammation. Scanning
      electron microscopy indicated that, when investigating platelet structure in
      disease, addition of TF, calcium or thrombin will mask disease-induced
      alterations associated with platelet activation. Therefore, washed platelets
      without any additives is preferred for morphological analysis. Furthermore,
      morphological and viscoelastic analysis confirmed that thrombin activation is the
      preferred method of fibrin activation when investigating fibrin network
      ultrastructure. 

PMID- 25772115
TI  - Clinical significance and management of subsegmental pulmonary embolism.
AB  - Computed tomographic pulmonary angiography (CTPA) has a high sensitivity for
      diagnosing filling defects in subsegmental pulmonary arteries. The adoption of
      CTPA as the preferred diagnostic modality for the diagnosis of pulmonary embolism
      (PE) has led to an increased rate of PE diagnosis. However, the case fatality
      rate is lower and the mortality rate of PE has remained unchanged despite this
      rise in PE diagnosis suggesting that the disease is of lesser severity. There
      continues to be clinical equipoise on whether patients diagnosed with isolated
      subsegmental PE (SSPE) require anticoagulation or can be managed conservatively
      if the presence of deep vein thrombosis (DVT) has been excluded. Recent
      recommendations from the European Society of Cardiology suggest an individualized
      approach for the management of patients with newly diagnosed SSPE based on the
      risk/benefit ratio of anticoagulation and the presence of lower limb DVT.
      Prospective data evaluating the safety and efficacy of management strategies for
      SSPE is needed in order to determine the optimal management of these patients.

PMID- 25772116
TI  - Engaging with quality improvement in anticoagulation management.
AB  - Anticoagulants are highly effective at preventing thrombosis across a variety of
      clinical indications. However, their use can also lead to devastating effects,
      including major bleeding and death. Anticoagulation providers strive to balance
      the benefits of anticoagulant therapy with the risks of major bleeding. A measure
      of quality care can be used to assess the strengths and potential weaknesses in
      any system of coordinated care delivery. Quality measures in anticoagulation
      include patient-centered outcomes (e.g. major bleeding, time in the therapeutic
      range) and provider- or process-focused outcomes (e.g. compliance with guideline
      recommendations and response times to out-of-range laboratory values). Engaging
      in quality improvement activities allows anticoagulation providers to assess
      their own performance and identify areas for targeted interventions. This review
      summarizes the justification for engaging in quality improvement for
      anticoagulation management and describes a number of example programs.
      Interventions benefiting the management of both warfarin and the direct oral
      anticoagulants are included. The review also details potential quality measures
      and resources for any anticoagulation provider looking to begin a quality
      improvement process. 

PMID- 25772117
TI  - Occurrence of Depressive Symptoms Among Older Adults after a Stroke in the
      Nursing Home Facility.
AB  - PURPOSE: The aim of the study was to analyze the prevalence of depressive
      symptoms among older adults after stroke in a nursing home (NH). DESIGN: The
      study was conducted in a NH and included 50 patients after stroke with a mean age
      of 74.62 (+/-8.2). METHOD: The Mini Mental State Examination (MMSE), Geriatric
      Depression Scale (GDS), Acceptance Illness Scale (AIS) and Barthel Index (BI)
      were used. FINDINGS: Mean GDS was 7.60 (+/-2.75); 74% of patients had depressive
      symptoms. The study showed a significant relationship between GDS and marital
      status (p = .043). A negative correlations between GDS and MMSE (p = .029), GDS
      and BI (p = .049), and GDS and AIS (p < .0001) were found. CONCLUSION: The
      occurrence of depressive symptoms in older adults after stroke depends on their
      mental and functional status, degree of acceptance of illness, and marital
      status. CLINICAL RELEVANCE: Early detection of depressive symptoms in stroke
      patients allows rehabilitation nurses to optimize the therapeutic effects.

PMID- 25772119
TI  - Deaths linked to synthetic cannabinoids.

PMID- 25772118
TI  - Heme oxygenase-1 and heme oxygenase-2 expression in bruises.
AB  - The first step in catabolism of hemoglobin in a bruise is performed by the enzyme
      heme oxygenase, which produces biliverdin that is then reduced to bilirubin. The
      development of yellow coloration in bruises can be attributed to local
      accumulation of degradation products of hemoglobin, including bilirubin, but it
      is not clear why there is a delay before this color change is apparent. One
      explanation may be that time is required for the establishment of heme oxygenase
      activity at the bruise site. This study used immunohistochemistry to examine the
      time course of expression of heme oxygenase-1 and heme oxygenase-2 in a rat
      bruise model. Heme oxygenase-1 levels rose above background from 6 h to peak from
      days 1 to 3. There was strong expression by macrophages, but only occasional
      neutrophils expression of heme oxygenase-1. Heme oxygenase-2 did not change
      significantly from background levels. The results suggest that the delay in the
      development of yellow coloration of bruises may in part be attributed to the
      requirement for macrophages to be recruited to the site of injury. 

PMID- 25772120
TI  - Use of a non-volatile agent to stabilize severely incinerated dental remains.
AB  - PURPOSE: The aim of this study was to identify volatile-free products that would
      be suitable for stabilizing incinerated dental remains at the scene of an
      incident, and that would not compromise any postmortem examination. METHODS: The
      anterior mandibles of sheep were incinerated, sprayed unilaterally with
      stabilizing agents, vibrated for 30 s, and assessed. The effect of the
      stabilizing solutions on radiographic examination was also recorded. Tests for
      volatility and the effect on human mandibles were also conducted. RESULTS: A
      flour/water mixture of one part flour to two parts water, and a paste mixture of
      one part ClagTM glue to one part water both produced significant stabilization
      results. The flour mixture left an opaque layer on the samples that it was
      applied to, which still allowed dental examination, but the glue paste mixture
      resulted in a clearer layer. Both solutions allowed radiographic examination and
      were free of volatiles. CONCLUSION: Diluted ClagTM paste, when sprayed on to
      incinerated remains, assists in their stabilization for transportation. When
      ClagTM paste is unavailable a mixture of two parts water to one part plain flour
      could be utilized for stabilization.

PMID- 25772121
TI  - Diagnostic criteria for cutaneous injuries in child abuse: classification,
      findings, and interpretation.
AB  - Physical abuse of children has many manifestations. Depending on the type of
      force involved, specific injury patterns are produced on the body of the child,
      the morphology and localization of which are forensically relevant in terms of
      diagnostic classification as child abuse. Typical patterned bruising includes,
      for example, tramline bruises resulting from blows with oblong, stick-like
      objects. In addition to rounded or one-sided horseshoe-shaped bite injuries,
      injuries of different ages, clustered injuries (e.g., three or more individual
      injuries in the same body region), and thermal injuries are typical results of
      abuse. Abusive scalds are usually characterized by a symmetrical impression and
      localization with sharp delineation of the scald wound edges, in contrast to
      accidental scalding injuries with radiating splash patterns ending in tapered
      points. The coloration of a hematoma can help indicate the time when the injury
      occurred. Lack of a coherent and comprehensible explanation for accidental injury
      constitutes grounds for suspecting abuse. Suspicions should be raised in cases of
      a delayed visit to a doctor, waiting for an unusually long period before
      summoning emergency medical help for serious injuries to a child, and when
      differing versions of a purported accident are provided. Documentation of the
      findings is highly relevant in later reviews of the diagnosis, for instance, when
      new relevant facts and investigative results come to light in subsequent criminal
      proceedings. 

PMID- 25772122
TI  - Amending the anisotropy barrier and luminescence behavior of heterometallic
      trinuclear linear [M(II) -Ln(III) -M(II) ] (Ln(III) =Gd, Tb, Dy; M(II) =Mg/Zn)
      complexes by change from divalent paramagnetic to diamagnetic metal ions.
AB  - The sequential reaction of a multisite coordinating compartmental ligand [2-(2
      hydroxy-3-(hydroxymethyl)-5-methylbenzylideneamino)-2-methylpropane-1,3-diol]
      (LH4 ) with appropriate lanthanide salts followed by the addition of [Mg(NO3 )2
      ]?6 H2 O or [Zn(NO3 )2 ]?6 H2 O in a 4:1:2 stoichiometric ratio in the presence
      of triethylamine affords a series of isostructural heterometallic trinuclear
      complexes containing [Mg2 Ln](3+) (Ln=Dy, Gd, and Tb) and [Zn2 Ln](3+) (Ln=Dy,
      Gd, and Tb) cores. The formation of these complexes is demonstrated by X-ray
      crystallography as well as ESI-MS spectra. All complexes are isostructural
      possessing a linear trimetallic core with a central lanthanide ion. The
      comprehensive studies discussed involve the synthesis, structure, magnetism, and
      photophysical properties on this family of trinuclear [Mg2 Ln](3+) and [Zn2
      Ln](3+) heterometallic complexes. [Mg2 Dy](3+) and [Zn2 Dy](3+) show slow
      relaxation of the magnetization below 12 K under zero applied direct current (dc)
      field, but without reaching a neat maximum, which is due to the overlapping with
      a faster quantum tunneling relaxation mediated through dipole-dipole and
      hyperfine interactions. Under a small applied dc field of 1000 Oe, the quantum
      tunneling is almost suppressed and temperature and frequency dependent peaks are
      observed, thus confirming the single-molecule magnet behavior of complexes [Mg2
      Dy](3+) and [Zn2 Dy](3+) .

PMID- 25772123
TI  - The professionalisation of Irish medicine in the generations before Charles
      Lucas.
AB  - The educational opportunities and qualifications, corporate structures and
      regulation that had become accepted features of the Irish medical profession in
      the era of Charles Lucas were the fruits of a slow process of professionalization
      initiated by a handful of Irish medics who, from the 1620s, began tackling poor
      standards of medical practice in an era of medical pluralism. This paper begins
      by reviewing the standard of practice in early seventeenth-century Ireland.
      Through the examples of Thomas Arthur, M.D. and John Clavell, a self-styled
      medic, differences in the approaches adopted by university-trained physicians and
      unorthodox practitioners are highlighted. The succession of significant steps
      taken in this professionalization process are traced, with particular emphasis on
      the failed attempt to establish a Royal College of Physicians in Dublin during
      the mid-1620s and the importance of the influx of English physicians in the 1650s
      for the creation of permanent corporate structures and regulation. 

PMID- 25772124
TI  - A novel rapid access testicular cancer clinic: prospective evaluation after one
      year.
AB  - BACKGROUND: Our institution has recently developed a rapid access outpatient
      clinic to investigate men with testicular lumps and/or pain suspicious for
      testicular cancer (TCa). AIMS: To present our experience after 12 months.
      METHODS: All referrals to the rapid access testicular clinic (RATC) clinic were
      prospectively analysed from 01/01/2013 to 01/01/2014. The primary outcome
      variable was incidence of TCa in the referred patient cohort. Secondary outcome
      variables were waiting times prior to clinical review and waiting times prior to
      radical orchidectomy in patients diagnosed with TCa. RESULTS: Seventy-four new
      patients were referred to the RATC during the 1-year period and the mean age was
      34 (range 15-81 years). TCa was the most common diagnosis and was found in 18 (25
      %) patients. Patients diagnosed with TCa underwent radical orchidectomy, a median
      of 3 (range 1-5) days after their initial GP referral. Patients requiring
      surgical intervention for benign scrotal pathology underwent their procedure a
      median of 32 (range 3-61) days after their initial referral. Of the 18 patients
      diagnosed with TCa, 9 (50 %) were diagnosed with a seminomatous germ cell tumour
      on histopathology. CONCLUSION: The RATC is a new initiative in Ireland that
      provides expedient and definitive treatment of patients with newly diagnosed TCa.
      Early treatment will ultimately improve long-term prognosis in this patient
      cohort.

PMID- 25772125
TI  - Implementation of a surgical handover tool in a busy tertiary referral centre: a
      complete audit cycle.
AB  - BACKGROUND: The implementation of the European work-time directive has created
      increased transitions of care during weekends as doctors adhere to a shift-work
      structure. This raises concerns over continuity of care and patient safety. To
      address this, doctors must develop a time efficient yet safe system of handover
      of patients to the team on-call. Intuitively weekend care provides the ideal
      setting to develop a handover tool. AIM: To develop and implement a process of
      surgical handover and to improve weekend discharge rate on a surgical service.
      METHODS: Data was collected at three time-points over a 6 months period (October
      2013-March 2014) encompassing development, implementation, re-evaluation and
      modification of the handover process. The outcomes measured were: number of
      inpatients, number of weekend discharges, length of stay (LOS) of inpatients
      recorded for the four weekends within the month, and total emergency response
      team (ERT) calls each month. RESULTS: Mean number of included patients each month
      was 294 (sigma = 14). Following the introduction of weekend handover there was a
      40 % increase in weekend discharges which was consistent for subsequent time
      points (p < 0.05). Following the second intervention there was a statistically
      significant reduction in mean LOS from 13 to 5.4 days (p < 0.05) and the total
      number of ERT calls for the month reduced from 12 to 4 (p < 0.05). CONCLUSIONS:
      The standardisation of weekend handover using a combination of an electronic tool
      supplemented with verbal handover is feasible. It resulted in a significant
      improvement in surrogate markers of patient care quality.

PMID- 25772126
TI  - The Irish contribution to the plastic surgery literature: 21 years of
      publications.
AB  - INTRODUCTION: The Republic of Ireland has always had an influence on medicine and
      has produced many renowned doctors who have helped shape its history.
      Furthermore, many clinical articles that have originated from Ireland have
      changed clinical practice throughout the world. The Irish have also had an impact
      on the plastic surgery literature yet it has never specifically been analyzed
      before. The purpose of this study was to identify and analyze all papers that
      have originated from the plastic surgery units in the Republic of Ireland in the
      medical literature over the past 21 years. METHODOLOGY: Twenty-four well-known
      plastic surgery, hand surgery and burns journals were selected for this study. By
      utilizing Scopus, the largest abstract and citation database of peer-reviewed
      literature, we analyzed each of our chosen 24 journals looking for Irish
      publications. Each paper was examined for article type, authorship, year of
      publication, institution of origin and level of evidence. RESULTS: Papers from
      the Republic of Ireland were published in 20 of the 24 journals over the past 21
      years. A total of 245 articles from Ireland were published in the plastic
      surgery, hand surgery and burns literature over the 21-year period. Of these, 111
      were original articles and 73 were case reports. The institution that published
      the most papers over the past 21 years was University Hospital Galway (66
      publications) followed by Cork University Hospital with 54 papers. The journal
      with the most Irish articles was the Journal of Plastic, Reconstructive and
      Aesthetic Surgery with 56 papers. 2014 was the year with the most publications
      (28 papers). Authorship numbers also increased over time as the average number of
      authors in 1994 was 3.5, whereas it was 5.54 in 2014. DISCUSSION: The number of
      publications per year continues to increase along with authorship numbers. This
      mirrors the trend in other specialties. Publications are now no longer required
      for selection on to a higher surgical training scheme. There is now a fear that
      the academic output of trainees will decrease as a consequence. To prevent this,
      each unit must actively support and encourage research activity with their
      trainees.

PMID- 25772127
TI  - Significant reduction in alcohol-related admissions to an intensive care unit in
      Dublin.
AB  - BACKGROUND: In 2008, we conducted an audit in our general intensive care unit
      (ICU) which demonstrated a high workload from alcohol-related admissions which
      represented 12 % of total admissions and 16.8 % of total available bed days at
      that time. AIMS: To repeat the audit 5 years later in 2013 to assess the current
      workload from alcohol-related admissions and whether this had increased or
      decreased in the intervening time period. METHODS: We retrospectively collected
      data from every admission to our 17-bed general ICU for the 6-month period from
      June 1 2013 to November 30 2013. We identified all admissions that were related
      to alcohol misuse. Their admission diagnosis, age, gender, ICU length of stay,
      APACHE 2 score (Acute Physiology and Chronic Health Evaluation 2) and 30-day
      mortality were recorded. The results of the 2013 audit were then compared with
      data from the 2008 study. RESULTS: There were 30 % less alcohol-related
      admissions to our ICU in 2013 compared to the same period in 2008. The study
      group had a longer length of stay on average but a lower mortality than the
      control group. CONCLUSION: There has been a significant reduction in the ICU
      workload from alcohol-related admissions in our general ICU in the past 5 years.

PMID- 25772128
TI  - The Best of Both Worlds: Psychiatry Training at Combined Civilian-Military
      Programs.
AB  - Air Force psychiatry faces the task of training competent military psychiatrists
      in an era of continuing reductions. Beginning in the 1980s, the Air Force started
      collaborating with University partners to create hybrid training programs,
      civilian-military psychiatry residencies. These mergers provide stability for Air
      Force psychiatry training in the face of increased operational missions and
      uncertain military recruiting. As a result of these combined programs, Air Force
      psychiatry residents gain access to a broader range of civilian clinical
      experience and expertise while maintaining a focus on distinctive military
      requirements. The combining of programs opens up options for academic activities
      which may not have otherwise existed. Both military and civilian residents
      benefit from the occupational psychiatry experiences available within military
      clinical sites. These programs give civilian residents a chance to assist active
      duty members and their families and provide insight into the military
      "lifecycle." These collaborations benefit the universities by providing access to
      a larger pool of residents and faculty. The synthesis of the military and
      civilian programs raises some ongoing obstacles such as civilian residents'
      ability to gain access to military resources. The programs must also accommodate
      separate mechanisms for selecting residents (the National Residency Matching
      Program versus the Joint Selection Board for Graduate Medical Education).
      Military residents must also comply with military standards and requirements
      while maintaining the universities' standards of conduct and professionalism.
      Merging military training programs into university programs creates a vibrant
      opportunity to create exceptional military and civilian psychiatrists. 

PMID- 25772129
TI  - What Do Medical Students Perceive as Meaningful in the Psychiatry Clerkship
      Learning Environment? A Content Analysis of Critical Incident Narratives.
AB  - OBJECTIVES: In order to better understand the professional development of medical
      students during their psychiatry clerkship, this study identifies common themes
      and characteristics of students' critical incident narratives which are designed
      to capture a recount of clerkship experiences they perceived as meaningful.
      METHODS: A total of 205 narratives submitted by psychiatry clerkship students in
      2010-2011 were subjected to a thematic analysis using a methodological approach
      and adaptation of categories derived from prior similar research. Descriptive
      content analysis was also carried out to assess the valence of the narrative
      content, characters involved, and whether there was evidence that the experience
      changed students' perspectives in some way. RESULTS: Narratives contained a
      variety of positive (19%) and negative content (24%) and many contained a hybrid
      of both (57%). The most common theme (29%) concerned issues of respect and
      disrespect in patient, clinical, and coworker interactions. In general, the
      majority (68%) of students' meaningful experience narratives reflected a change
      in their perspective (e.g., I learned that...). Narratives containing positive
      and hybrid content were associated with a change in students' perspective (chi(2)
      = 10.61, df = 2, p < 0.005). CONCLUSIONS: Medical students are keenly aware of
      the learning environment. Positive and hybrid critical incident narratives were
      associated with a stated change in their beliefs, attitudes, or behaviors due to
      the experience. Understanding the events that are meaningful to students can also
      provide rich feedback to medical educators regarding the ways in which students
      perceive clinical learning environments and how to best foster their professional
      development.

PMID- 25772130
TI  - A call for better methodology for global mental health educational program
      reviews.

PMID- 25772131
TI  - Increased incidence of malignant melanoma and other rare cutaneous cancers in the
      setting of chronic lymphocytic leukemia.
AB  - BACKGROUND: Patients with chronic lymphocytic leukemia (CLL), small lymphocytic
      lymphoma (SLL), or non-Hodgkin lymphoma (NHL) are at increased risk for the
      development of skin malignancies. OBJECTIVES: This study was conducted to
      estimate the incidences of rare skin malignancies in patients with CLL/SLL or
      NHL. METHODS: Patients with a diagnosis of CLL/SLL or NHL recorded in the
      Surveillance, Epidemiology and End Results (SEER) database during 1992-2007 were
      identified. Diagnoses of specific skin malignancies were identified from SEER
      files. RESULTS: During 1992-2007, a total of 128,674 patients with first
      diagnoses of CLL/SLL or NHL were recorded in SEER; 4743 were excluded because
      follow-up data were unavailable. Among the remaining 123,931 patients, 28,964 had
      CLL/SLL and 94,967 had NHL. Standardized incidence ratios (SIRs) for invasive
      malignant melanoma, Merkel cell carcinoma, malignant fibrous histiocytoma,
      dermatofibrosarcoma protuberans, Kaposi's sarcoma, and sebaceous carcinoma were
      2.3, 8.2, 3.6, 2.5, 2.9, and 1.4, respectively, in CLL/SLL patients and 1.6, 3.2,
      1.5, 1.3, 17.6, and 0.8, respectively, in NHL patients. When invasive melanoma
      was stratified by patient age and sex, the highest SIR (17.8) was found in men
      aged 0-49 years with CLL (P < 0.001). CONCLUSIONS: Patients with CLL/SLL or NHL
      have a higher risk for the subsequent development of rare skin cancers. Given the
      more aggressive nature of these malignancies in this setting, regular monitoring
      for the development and prompt treatment of cutaneous malignancy is prudent in
      patients with NHL and particularly in patients with CLL. Regular use of sun
      protection may decrease the morbidity associated with skin cancer in this
      immunosuppressed population.

PMID- 25772132
TI  - Midterm outcomes of gastric bypass for elderly (aged >= 60 yr) patients: a
      comparative study.
AB  - BACKGROUND: Laparoscopic Roux-en-Y gastric bypass (LRYGB) is feasible for
      patients aged 60 years and older and is associated with a favorable early weight
      loss. However, data with longer follow-up in this age group are scarce. The
      present study compared weight loss and changes in co-morbidities 3 years after
      LRYGB between older patients (OP; >= 60 yr) and younger patients (YP; <60 yr).
      Data were collected prospectively in a single surgery university center (Paris,
      France). METHODS: Between January 2004 and May 2011, 48 OP and 610 YP underwent
      LRYGB. Three-year outcomes were available for 42 (87.5%) OP and 480 (78.7%) YP;
      42 OP undergoing LRYGB were matched with 84 YP for sex, preoperative body mass
      index (BMI), and presence of type 2 diabetes. RESULTS: The sample was 81% female;
      preoperative BMI was 45.6 +/- 6.4 kg/m2 in OP versus 47.3 +/- 5.2 kg/m2 in YP
      patients (P = .12), and age was 62.6 +/- 2.3 years in OP versus 42.9 +/- 8.7
      years in YP (P < .0001). The prevalence of coexisting conditions was comparable
      in both groups except for dyslipidemia (66.7% in OP versus 42.9% in YP; P = .01).
      At 3 years, percentage of weight loss and BMI change (kg/m2) was significantly
      lower in the OP group compared with YP (27.5 +/- 8.6 versus 31.8 +/- 12.1, P =
      .04; and -12.7 +/- 4.9 versus -15.2 +/- 6.2, P = .03). The rate of remission of
      hypertension was lower in OP than in YP (18.8% versus 53.8%; P = .002), as was
      that of both obstructive sleep apnea (60.6% versus 87.9%; P = .004) and
      dyslipidemia (42.9% versus 75.0%; P = .01). CONCLUSIONS: At 3 years, despite less
      favorable impact on weight than for younger patients, LRYGB provided significant
      weight loss and remission of co-morbidities for patients aged > 60 years. Long
      term trials are needed to better evaluate the benefit of bariatric surgery in
      aging obese patients.

PMID- 25772133
TI  - Haplotype combination of the bovine CFL2 gene sequence variants and association
      with growth traits in Qinchuan cattle.
AB  - The aim of this study was to examine the association of cofilin2 (CFL2) gene
      polymorphisms with growth traits in Chinese Qinchuan cattle. Three single
      nucleotide polymorphisms (SNPs) were identified in the bovine CFL2 gene using DNA
      sequencing and (forced) PCR-RFLP methods. These polymorphisms included a missense
      mutation (NC_007319.5: g. C 2213 G) in exon 4, one synonymous mutation
      (NC_007319.5: g. T 1694 A) in exon 4, and a mutation (NC_007319.5: g. G 1500 A)
      in intron 2, respectively. In addition, we evaluated the haplotype frequency and
      linkage disequilibrium coefficient of three sequence variants in 488 individuals
      in QC cattle. All the three SNPs in QC cattle belonged to an intermediate level
      of genetic diversity (0.25<PIC<0.5). Haplotype analysis of three SNPs showed that
      8 different haplotypes were identified in all, but only 5 haplotypes were listed
      except for those with a frequency of <0.03. Hap4 (-GTC-) had the highest
      haplotype frequencies (34.70%). However in the three SNPs there were no
      significant associations between the 13 combined genotypes of the CFL2 gene and
      growth traits. LD analysis showed that the SNP T 1694 A and C 2213 G loci had a
      strong linkage (r(2)>0.33). Association analysis indicated that SNP G 1500 A, T
      1694 A and C 2213 G were significantly associated with growth traits in the QC
      population. The results of our study suggest that the CFL2 gene may be a strong
      candidate gene that affects growth traits in the QC cattle breeding program.

PMID- 25772136
TI  - Mavridis' area and electrode target localization in nucleus accumbens deep brain
      stimulation.

PMID- 25772137
TI  - Two swine models of iliac vein occlusion: Which form most contributes to venous
      thrombosis?
AB  - OBJECTIVES: In the present study, we establish two swine models of iliac vein
      occlusion (IVO) with spontaneous thrombosis to understand the mechanisms linking
      IVO and thrombosis. METHODS: Two IVO models were established in 12 swine either
      by ligating the common iliac vein (CIVO) or both the common and external iliac
      veins (CEIVO). Venography was performed to assess each model and the associated
      thrombosis. Invasive blood pressure was also measured, and the vessels were
      examined histologically to analyse the pathological changes after ligation.
      RESULTS: On venography, the CIVO model showed common iliac vein (CIV) occlusion
      and reflux in the collateral veins whereas the CEIVO model showed occlusion in
      the CIV and external iliac vein (EIV), stasis in the EIV, and decreased
      collateral vasculature on venography. Thrombosis was only observed in the CEIVO
      model, which was with significantly higher venous blood pressure in the EIV and
      with significantly more thickened venous wall with lymphocytic infiltration
      histologically. CONCLUSIONS: Two IVO models can be feasibly and reliably
      established in swine. The CEIVO model had a higher prevalence of thrombosis than
      the CIVO model. This CEIVO model produces comparatively less collateral drainage
      and greater inflammation that can contribute to the thrombosis prone to this type
      of model.

PMID- 25772138
TI  - Bivalirudin as compared to unfractionated heparin in patients undergoing
      percutaneous coronary revascularization: A meta-analysis of 22 randomized trials.
AB  - Bivalirudin has gained ground against unfractionated heparin (UFH) in
      percutaneous coronary interventions (PCI), due to a reported better safety
      profile. However, whether bivalirudin may provide also advantages in clinical
      outcome beyond the known benefits in major bleedings, is still a debated matter
      and was, therefore, the aim of present meta-analysis of randomized trials,
      evaluating efficacy and safety of bivalirudin as compared with UFH in PCI.
      METHODS AND STUDY OUTCOMES: Literature archives (Pubmed, EMBASE, Cochrane) and
      main scientific sessions were scanned. Primary endpoint was overall mortality.
      Secondary endpoints were: 1) mortality within 30-days; 2) overall and within 30
      days non fatal myocardial infarction; 3) overall and within 30-days stent
      thrombosis. Safety endpoints were major bleedings (per protocol definition or
      TIMI classification). A prespecified analysis was conducted according to clinical
      presentation (Elective, ACS, STEMI). RESULTS: A total of 22 randomized clinical
      were finally included, involving 40156 patients randomized to bivalirudin (52.9%)
      or to UFH (47.1%). Death occurred in 1100 (2.8%) of patients, with no difference
      between bivalirudin and UFH (2.7% vs 2.8% OR[95%C]=0.94[0.83,-.06], p=0.32,
      phet=0.48). The results did not change according to clinical presentation. By
      meta-regression analysis, the effects on mortality were not related to patients
      risk profile (r=-0.38(-0.89-0.14), p=0.15) or the reduction in bleeding
      complications (r=-0.008(-0.86-0.85), p=0.98). A significant increase in short
      term stent thrombosis was observed with bivalirudin (OR[95%CI]=1.42 [1.10-1.83],
      p=0.006). However, Bivalirudin significantly reduced bleedings according to both
      study protocol definition (OR[95%CI]=0.62[0.56-0.69],p<0.00001; phet=0.0003) or
      TIMI major criteria (OR[95%CI]=0.65[0.53-0.79],p<0.0001, phet=0.95). CONCLUSIONS:
      In present meta-analysis, among patients undergoing PCI, bivalirudin, as compared
      with UFH, is associated with a significant reduction in major bleeding
      complications that, however, does not translate into mortality benefits.
      Furthermore, bivalirudin is associated with higher rate of 30-days stent
      thrombosis and recurrent MI among STEMI patients.

PMID- 25772139
TI  - Expression and Cell Distribution of SENP3 in Brain Tissue After Traumatic Brain
      Injury in Mice: A Pilot Study.
AB  - SUMO-specific proteases 3 (SENP3) is a member of the small ubiquitin-like
      modifier-specific protease family and deconjugates SUMO2/3 from protein
      substrates. To date, the expression and function of SENP3 in traumatic brain
      injury (TBI) are unclear. The present study examined dynamic changes in SENP3
      expression in the cerebral cortex and in its cellular localization, using an
      acute TBI model in adult mice. SENP3 expression was examined at 3, 6, 12, 24 h,
      3, and 5 days after TBI using Western Blot analysis and quantitative real-time
      PCR. Immunohistochemistry and immunofluorescence were examined to detect SENP3
      localization. Western Blot indicated that SENP3 protein levels gradually
      increased from 3 h after TBI and peaked at 24 h. Quantitative real-time PCR
      demonstrated a gradual increase in SENP3 expression, which peaked 12 h after TBI
      and declined subsequently. Immunohistochemical staining demonstrated that SENP3
      positive cells were observed in both the sham and 24 h post-TBI groups. However,
      robust expression of SENP3 was seldom observed in the sham group, while it was
      notably enhanced after TBI. Furthermore, immunofluorescence results revealed that
      the expression of SENP3 increased more significantly in neurons at day 1 after
      TBI compared with sham group and less significantly in astrocytes and microglia.
      Moreover, the SENP3-positive cells that were co-expressed with NeuN also
      expressed caspase-3, indicating a potential correlation between SENP3 and
      apoptosis after TBI. Collectively, our results showed obvious up-regulation of
      SENP3 expression in the brain after TBI, especially in the neurons. However, the
      full role of SENP3 and its therapeutic potential in TBI needs further
      investigation.

PMID- 25772140
TI  - The Internalization of Neurotensin by the Low-Affinity Neurotensin Receptors
      (NTSR2 and vNTSR2) Activates ERK 1/2 in Glioma Cells and Allows Neurotensin
      Polyplex Transfection of tGAS1.
AB  - Glioblastoma is the most malignant primary brain tumor and is very resistant to
      treatment; hence, it has a poor prognosis. Neurotensin receptor type 1 (NTSR1)
      plays a key role in cancer malignancy and has potential therapeutic applications.
      However, the presence and function of neurotensin (NTS) receptors in glioblastoma
      is not clearly established. RT-PCR assays showed that healthy (non-tumor)
      astroglial cells and C6 glioma cells express NTSR2 and its isoform (vNTSR2)
      rather than NTSR1. In glioma cells, NTS promotes the phosphorylation of
      extracellular signal-regulated kinases 1/2 (ERK 1/2), an effect that was
      completely abolished by blocking the internalization of the NTS/NTSR complex. We
      demonstrated pharmacologically that the internalization is dependent on the
      activation of NTSR2 receptors and it was prevented by levocabastine, a NTSR2
      receptor antagonist. The internalization of NTSR2 and vNTSR2 was further
      demonstrated by its ability to mediate gene transfer (transfection) via the NTS
      polyplex system. Expression of reporter transgenes and of the pro-apoptotic
      soluble form of growth arrest specific 1 (tGAS1) was observed in glioma cells. A
      significant reduction on the viability of C6 cells was determined when tGAS1 was
      transfected into glioma cells. Conversely, astroglial cells could neither
      internalize NTS nor activate ERK 1/2 and could not be transfected by the NTS
      polyplex. These results demonstrate that the internalization process of NTSR2
      receptors is a key regulator necessary to trigger the activation of the ERK 1/2.
      Our data support a new internalization pathway in glioma C6 cells that involve
      NTSR2/vNTSR2, which can be used to selectively transfer therapeutic genes using
      the NTS-polyplex system. 

PMID- 25772134
TI  - Engineering Stem Cells for Biomedical Applications.
AB  - Stem cells are characterized by a number of useful properties, including their
      ability to migrate, differentiate, and secrete a variety of therapeutic molecules
      such as immunomodulatory factors. As such, numerous pre-clinical and clinical
      studies have utilized stem cell-based therapies and demonstrated their tremendous
      potential for the treatment of various human diseases and disorders. Recently,
      efforts have focused on engineering stem cells in order to further enhance their
      innate abilities as well as to confer them with new functionalities, which can
      then be used in various biomedical applications. These engineered stem cells can
      take on a number of forms. For instance, engineered stem cells encompass the
      genetic modification of stem cells as well as the use of stem cells for gene
      delivery, nanoparticle loading and delivery, and even small molecule drug
      delivery. The present Review gives an in-depth account of the current status of
      engineered stem cells, including potential cell sources, the most common methods
      used to engineer stem cells, and the utilization of engineered stem cells in
      various biomedical applications, with a particular focus on tissue regeneration,
      the treatment of immunodeficiency diseases, and cancer. 

PMID- 25772142
TI  - Non-enzymatic electrochemical glucose sensor based on NiMoO4 nanorods.
AB  - A non-enzymatic glucose sensor based on the NiMoO4 nanorods has been fabricated
      for the first time. The electrocatalytic performance of the NiMoO4 nanorods'
      modified electrode toward glucose oxidation was evaluated by cyclic voltammetry
      and amperometry. The NiMoO4 nanorods' modified electrode showed a greatly
      enhanced electrocatalytic property toward glucose oxidation, as well as an
      excellent anti-interference and a good stability. Impressively, good accuracy and
      high precision for detecting glucose concentration in human serum samples were
      obtained. These excellent sensing properties, combined with good reproducibility
      and low cost, indicate that NiMoO4 nanorods are a promising candidate for non
      enzymatic glucose sensors. 

PMID- 25772141
TI  - Ornithine In Vivo Administration Disrupts Redox Homeostasis and Decreases
      Synaptic Na(+), K (+)-ATPase Activity in Cerebellum of Adolescent Rats:
      Implications for the Pathogenesis of Hyperornithinemia-Hyperammonemia
      Homocitrullinuria (HHH) Syndrome.
AB  - Hyperornithinemia-hyperammonemia-homocitrullinuria (HHH) syndrome is an inborn
      error of metabolism caused by a defect in the transport of ornithine (Orn) into
      mitochondrial matrix leading to accumulation of Orn, homocitrulline (Hcit), and
      ammonia. Affected patients present a variable clinical symptomatology, frequently
      associated with cerebellar symptoms whose pathogenesis is poorly known. Although
      in vitro studies reported induction of oxidative stress by the metabolites
      accumulating in HHH syndrome, so far no report evaluated the in vivo effects of
      these compounds on redox homeostasis in cerebellum. Therefore, the present work
      was carried out to investigate the in vivo effects of intracerebellar
      administration of Orn and Hcit on antioxidant defenses (reduced glutathione
      concentrations and the activities of superoxide dismutase, catalase, glutathione
      peroxidase, glutathione reductase, and glucose-6-phosphate dehydrogenase), lipid
      oxidation (malondialdehyde concentrations), as well as on the activity of
      synaptic Na(+), K(+)-ATPase, an enzyme highly vulnerable to free radical attack,
      in the cerebellum of adolescent rats. Orn significantly increased malondialdehyde
      levels and the activities of all antioxidant enzymes, and reduced Na(+), K(+)
      ATPase activity. In contrast, glutathione concentrations were not changed by Orn
      treatment. Furthermore, intracerebellar administration of Hcit was not able to
      alter any of these parameters. The present data show for the first time that Orn
      provokes in vivo lipid oxidative damage, activation of the enzymatic antioxidant
      defense system, and reduction of the activity of a crucial enzyme involved in
      neurotransmission. It is presumed that these pathomechanisms may contribute at
      least partly to explain the neuropathology of cerebellum abnormalities and the
      ataxia observed in patients with HHH syndrome. 

PMID- 25772143
TI  - Modeling an irritant gas plume for epidemiologic study.
AB  - Plume dispersion modeling systems are often used in assessing human exposures to
      chemical hazards for epidemiologic study. We modeled the 2005 Graniteville, South
      Carolina, 54,915 kg railcar chlorine release using both the Areal Locations of
      Hazardous Atmospheres and Hazard Prediction and Assessment Capability (HPAC)
      plume modeling systems. We estimated the release rate by an engineering analysis
      combining semi-quantitative observations and fundamental physical principles. The
      use of regional meteorological conditions was validated by comparing
      concentration estimates generated by two source-location weather data-sets. The
      HPAC model estimated a chlorine plume with 20 ppm outdoor concentrations up to 7
      km downwind and 0.25 km upwind/downgrade. A comparative analysis of our two
      models showed that HPAC was the best candidate for use as a model system on which
      epidemiologic studies could be based after further model validation. Further
      validation studies are needed before individual exposure estimates can be
      reliable and the chlorine plume more definitively modeled. 

PMID- 25772145
TI  - Tip enhancement of upconversion photoluminescence from rare earth ion doped
      nanocrystals.
AB  - We present tip-enhanced upconversion photoluminescence (PL) images of Er(3+)- and
      Yb(3+)-doped NaYF4 nanocrystals on glass substrates with subdiffraction spatial
      resolution. Tip-sample distance dependent measurements clearly demonstrate the
      near-field origin of the image contrast. Time-resolved PL measurements show that
      the tip increases the spontaneous emission rate of the two emission channels of
      Er(3+) in the visible region. Very efficient enhancement of upconversion PL is
      discussed in the context of the two-photon nature of the excitation process and
      homoenergy transfer between the ions within the nanocrystals. Comparison between
      different nanocrystals and tips shows a strong influence of the tip shape on the
      image contrast that becomes particularly relevant for the larger dimensions of
      the investigated nanocrystals. 

PMID- 25772144
TI  - Evaluation of an intramedullary bone stabilization system using a light-curable
      monomer in sheep.
AB  - Percutaneous intramedullary fixation may provide an ideal method for
      stabilization of bone fractures, while avoiding the need for large tissue
      dissections. Tibiae in 18 sheep were treated with an intramedullary photodynamic
      bone stabilization system (PBSS) that comprised a polyethylene terephthalate
      (Dacron) balloon filled with a monomer, cured with visible light in situ, and
      then harvested at 30, 90, or 180 days. In additional 40 sheep, a midshaft tibial
      osteotomy was performed and stabilized with external fixators or external
      fixators combined with the PBSS and evaluated at 8, 12, and 26 weeks. Healing and
      biocompatibility were evaluated by radiographic analysis, micro-computed
      tomography, and histopathology. In nonfractured sheep tibiae, PBSS implants
      conformably filled the medullary canal, while active cortical bone remodeling and
      apposition of new periosteal and/or endosteal bone was observed with no
      significant macroscopic or microscopic observations. Fractured sheep tibiae
      exhibited increased bone formation inside the osteotomy gap, with no significant
      difference when fixation was augmented by PBSS implants. Periosteal callus size
      gradually decreased over time and was similar in both treatment groups. No
      inhibition of endosteal bone remodeling or vascularization was observed with PBSS
      implants. Intramedullary application of a light-curable PBSS is a biocompatible,
      feasible method for fracture fixation.

PMID- 25772146
TI  - Protective effect of pioglitazone on sepsis-induced intestinal injury in a rodent
      model.
AB  - BACKGROUND: Pathogenesis and treatment of inflammatory gut barrier failure is an
      important problem in critical care. In this study, we examined the role of
      pioglitazone, an agonist of peroxisome proliferator-activated receptor gamma, in
      gut barrier failure during experimental peritonitis in rats. MATERIALS AND
      METHODS: Male rats were randomly divided into three groups as follows: sham,
      sepsis, and sepsis + pioglitazone. Sepsis was achieved by means of the cecal
      ligation and puncture (CLP). Pioglitazone was administered intraperitoneally (10
      mg/kg/d) for 7 d before the experiment. Animals were killed at 24 h or followed
      72 h for survival. The tissue level of tumor necrosis factor-alpha, interleukin
      6, superoxide dismutase, malondialdehyde, and myeloperoxidase was measured.
      Intestinal mucosa injury was assessed histologically. The plasma fluorescein
      isothiocyanate-dextran, D-lactic acid, and intestinal diamine oxidase were
      determined to evaluate the permeability and integrity of intestinal mucosal
      epithelium. Vena cava blood and tissue samples were used to monitor bacterial
      translocation. RESULTS: Intestinal inflammation, oxidize stress, neutrophil
      infiltration, morphology injury, and impaired permeability of the small intestine
      in the CLP group were found more severe than those in the sham group. Application
      of pioglitazone not only minimized all the indicators of intestinal injury and
      barrier failure but also improved the survival of septic rats induced by CLP.
      CONCLUSIONS: Our novel findings suggest that pioglitazone could protect against
      intestinal injury and maintain intestinal barrier integrity and might be a useful
      strategy to ameliorate intestinal failure in polymicrobial sepsis.

PMID- 25772147
TI  - Hepatocyte autophagy is linked to C/EBP-homologous protein, Bcl2-interacting
      mediator of cell death, and BH3-interacting domain death agonist gene expression.
AB  - BACKGROUND: Endoplasmic reticulum (ER) stress and autophagy each play important
      roles in hepatocyte cell injury. We hypothesized that gene expression of C/EBP
      homologous protein (CHOP) and the BH3 proteins Bcl2-interacting mediator of cell
      death (BIM) and BH3-interacting domain death agonist (BID) are involved in a
      complex interplay that regulates ER stress-induced autophagy and cell death.
      MATERIALS AND METHODS: Hepatocytes were cultured from lean Zucker rats. Confluent
      hepatocytes were incubated with single or combined small interfering RNA for
      CHOP, BIM, and/or BID for 24 h providing gene inhibition. Incubation with
      tunicamycin (TM) for another 24 h stimulated ER stress. Quantitative real-time
      polymerase chain reaction determined the expression levels of CHOP, BIM, and BID.
      Immunostaining with microtubule-associated protein 1 light chain 3 measured
      autophagy activity. Trypan blue exclusion determined the cell viability. RESULTS:
      TM treatment increased the messenger RNA levels of CHOP and BIM but decreased the
      messenger RNA levels of BID. TM increased autophagy and decreased cell viability.
      Individual inhibition of CHOP, BIM, or BID protected against autophagy and cell
      death. However, simultaneous treatment with any combination of CHOP, BIM, and BID
      small interfering RNAs reduced autophagy activity but increased cell death
      independent of ER stress induction. CONCLUSIONS: Autophagy in hepatocytes results
      from acute ER stress and involves interplay, at the gene expression level, of
      CHOP, BIM, and BID. Inhibition of any one of these individual genes during acute
      ER stress is protective against cell death. Conversely, inhibition of any two of
      the three genes results in increased nonautophagic cell death independent of ER
      stress induction. This study suggests interplay between CHOP, BIM, and BID
      expression that can be leveraged for protection against ER stress-related cell
      death. However, disruption of the CHOP/BH3 gene expression homeostasis is
      detrimental to cell survival independent of other cellular stress.

PMID- 25772148
TI  - Evidence for a boat conformation at the transition state of GH76 alpha-1,6
      mannanases--key enzymes in bacterial and fungal mannoprotein metabolism.
AB  - alpha-Mannosidases and alpha-mannanases have attracted attention for the insight
      they provide into nucleophilic substitution at the hindered anomeric center of
      alpha-mannosides, and the potential of mannosidase inhibitors as cellular probes
      and therapeutic agents. We report the conformational itinerary of the family GH76
      alpha-mannanases studied through structural analysis of the Michaelis complex and
      synthesis and evaluation of novel aza/imino sugar inhibitors. A Michaelis complex
      in an (O) S2 conformation, coupled with distortion of an azasugar in an inhibitor
      complex to a high energy B2,5 conformation are rationalized through ab initio
      QM/MM metadynamics that show how the enzyme surface restricts the conformational
      landscape of the substrate, rendering the B2,5 conformation the most
      energetically stable on-enzyme. We conclude that GH76 enzymes perform catalysis
      using an itinerary that passes through (O) S2 and B2,5 (?) conformations,
      information that should inspire the development of new antifungal agents. 

PMID- 25772149
TI  - Wilms tumor 1 peptide vaccination combined with temozolomide against newly
      diagnosed glioblastoma: safety and impact on immunological response.
AB  - To investigate the safety of combined Wilms tumor 1 peptide vaccination and
      temozolomide treatment of glioblastoma, a phase I clinical trial was designed.
      Seven patients with histological diagnosis of glioblastoma underwent concurrent
      radiotherapy and temozolomide therapy. Patients first received Wilms tumor 1
      peptide vaccination 1 week after the end of combined concurrent
      radio/temozolomide therapy, and administration was continued once per week for 7
      weeks. Temozolomide maintenance was started and performed for up to 24 cycles,
      and the observation period for safety encompassed 6 weeks from the first
      administration of maintenance temozolomide. All patients showed good tolerability
      during the observation period. Skin disorders, such as grade 1/2 injection-site
      reactions, were observed in all seven patients. Although grade 3 lymphocytopenia
      potentially due to concurrent radio/temozolomide therapy was observed in five
      patients (71.4 %), no other grade 3/4 hematological or neurological toxicities
      were observed. No autoimmune reactions were observed. All patients are still
      alive, and six are on Wilms tumor 1 peptide vaccination without progression,
      yielding a progression-free survival from histological diagnosis of 5.2-49.1
      months. Wilms tumor 1 peptide vaccination was stopped in one patient after 12
      injections by the patient's request. The safety profile of the combined Wilms
      tumor 1 peptide vaccination and temozolomide therapy approach for treating
      glioblastoma was confirmed. 

PMID- 25772150
TI  - Hydra viridissima (green Hydra) rapidly recovers from multiple magnesium pulse
      exposures.
AB  - The time taken for organisms to recover from a pulsed toxicant exposure is an
      important consideration when water quality guidelines are applied to intermittent
      events in the environment. Organisms may appear to have recovered by standard
      toxicity testing methods but could carry residual toxicant or damage that may
      make them more sensitive to subsequent pulses. Such cumulative effects may render
      guidelines underprotective. The present study evaluated recovery of the
      freshwater cnidarian Hydra viridissima following multiple pulse exposure to
      magnesium (Mg). The H. viridissima were exposed to 4-h pulses of 790 mg/L and
      1100 mg/L separated by 2-h, 10-h, 18-h, 24-h, 48-h, and 72-h recovery periods.
      Twenty-four-hour pulses of 570 mg/L, 910 mg/L, and 940 mg/L were separated by 24
      h, 96-h, and 168-h recovery periods. All treatments showed similar or reduced
      sensitivity to the second pulse when compared with the single pulse, indicating
      that full recovery occurred prior to a second pulse-exposure. Five variations of
      equivalent time-weighted average concentrations were used to compare sensitivity
      of Hydra with various pulse scenarios. The sensitivity of the organisms to the
      multiple pulses was significantly lower than the time-weighted average continuous
      exposure response in 3 of the 4 scenarios tested, indicating that the Hydra
      benefited from interpulse recovery periods. The findings will be utilized
      alongside those from other species to inform the use of a site-specific, duration
      based water quality guideline for Mg, and they provide an example of the use of
      empirical data in the regulation of toxicant pulses in the environment.

PMID- 25772151
TI  - Brimonidine Imprinted Hydrogels and Evaluation of Their Binding and Releasing
      Properties as New Ocular Drug Delivery Systems.
AB  - Molecular imprinting is a technique for preparation of specific polymeric
      receptors for recognition and selective binding of chemicals. Recently,
      molecularly imprinted soft contact lenses have been studied as novel ocular drug
      delivery systems. The aim of this work was to prepare, for the first time, a
      brimonidine (BRN) imprinted soft contact lens material and study of its binding
      and releasing properties in aqueous media. The hydrogels were prepared using
      hydroxyethyl methacrylate (HEMA) as a backbone monomer, methacrylic acid (MAA),
      methacrylamide (MAAM) and 4-vinylpyridine (4VP) as the functional monomers and
      ethylene glycol dimethacrylate (EGDMA) as a cross linker monomer. Different BRN:
      MAA molar ratios were also applied in feed composition of monomers to study the
      influence of molecular imprinting technique on their binding properties. The
      hydrogels were characterized by determination of their swelling and binding
      properties in water. Their loading and release properties were also studied using
      Korsmeyer-Peppas equation in normal saline (NaCl 0.9%) and artificial tear
      solution. Poly (HEMA-co-MAA) showed superior binding properties compared to other
      copolymers. Also molecular imprinting technique significantly increased the
      hydrogel affinity to drug. It was found that all molecularly imprinted polymers
      (MIPs) had higher affinity to BRN in comparison with nonimprinted polymers
      (NIPs). The optimized MIP hydrogel with BRN: MAA molar ratio of 1: 8 showed
      greater ability to drug loading and controlled release compared to other MIPs.
      The results of the present work indicated that molecular imprinting technique had
      a significant effect on improving loading capacity and sustaining drug release
      from hydrogels. 

PMID- 25772152
TI  - Improving Protein Stability and Controlling Protein Release by Adding Poly
      (Cyclohexane-1, 4-Diyl Acetone Dimethylene Ketal) to PLGA Microspheres.
AB  - The use of biodegradable polymers such as PLGA to encapsulate therapeutic
      proteins for their controlled release has received tremendous interest. However,
      an acidic environment caused by PLGA degradation productions leads to protein
      incomplete release and chemical degradation. The aim of this study was to develop
      novel PCADK/PLGA microspheres to improve protein stability and release behavior.
      Bovine serum albumin (BSA) incubated in PCADK and PLGA degradation products was
      investigated using sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS
      PAGE), size exclusion chromatography (SEC-HPLC), circular dichroism (CD) and
      fluorescence spectroscopy. Blended microspheres of PCADK/PLGA were prepared in
      different ratios and the release behaviors of the microspheres and the protein
      stability were then measured. The degradation properties of the microspheres and
      the pH inside the microspheres were systematically investigated by scanning
      electron microscopy (SEM) and confocal laser scanning microscopy (CLSM) to
      examine the mechanism of autocatalytic degradation and protein stability. BSA was
      more stable in the presence of PCADK monomers than it was in the presence of PLGA
      monomers, revealing that PCADK is highly compatible with this protein. PCADK/PLGA
      microspheres were successfully prepared, and 2/8 was determined to be the optimal
      ratio. Further, 43% of the BSA formed water-insoluble aggregates in the presence
      of PCADK/PLGA microspheres, compared with 57% for the PLGA microspheres,
      demonstrating that the BSA encapsulated in PCADK/PLGA blended microspheres was
      more stable than in PLGA microspheres. The PCADK/PLGA blended microspheres
      improved protein stability and release behavior, providing a promising protein
      drug delivery system. 

PMID- 25772153
TI  - Biochemical characterization of GM1 micelles-Amphotericin B interaction.
AB  - In this work a thorough characterization of the GM1 micelle-Amphotericin B (AmB)
      interaction was performed. The micelle formation as well as the drug loading
      occurs spontaneously, although influenced by the physicochemical conditions, pH
      and temperature. The chromatographic profile of GM1-AmB complexes at different
      molar ratios shows the existence of two populations. The differential absorbance
      of GM1, monomeric and aggregate AmB, allowed us to discriminate the presence of
      all of them in both fractions. Thus, we noted that at higher proportion of AmB in
      the complex, increases the larger population which is composed mainly of
      aggregated AmB. The physical behavior of these micelles shows that both GM1- AmB
      complexes were stable in solution for at least 30 days. However upon freeze
      thawing or lyophilization-solubilization cycles, only the smallest population,
      enriched in monomeric AmB, showed a complete solubilization. In vitro, GM1-AmB
      micelles were significantly less toxic on cultured cells than other commercial
      micellar formulations as Fungizone, but had a similar behavior to liposomal
      formulations as Ambisome. Regarding the antifungal activity of the new
      formulation, it was very similar to that of other formulations. The
      characterization of these GM1-AmB complexes is discussed as a potential new
      formulation able to improve the antifungal therapeutic efficiency of AmB. 

PMID- 25772155
TI  - Modified wideband three-dimensional late gadolinium enhancement MRI for patients
      with implantable cardiac devices.
AB  - PURPOSE: To study the effects of cardiac devices on three-dimensional (3D) late
      gadolinium enhancement (LGE) MRI and to develop a 3D LGE protocol for implantable
      cardioverter defibrillator (ICD) patients with reduced image artifacts. THEORY
      AND METHODS: The 3D LGE sequence was modified by implementing a wideband
      inversion pulse, which reduces hyperintensity artifacts, and by increasing
      bandwidth of the excitation pulse. The modified wideband 3D LGE sequence was
      tested in phantoms and evaluated in six volunteers and five patients with ICDs.
      RESULTS: Phantom and in vivo studies results demonstrated extended signal void
      and ripple artifacts in 3D LGE that were associated with ICDs. The reason for
      these artifacts was slab profile distortion and the subsequent aliasing in the
      slice-encoding direction. The modified wideband 3D LGE provided significantly
      reduced ripple artifacts than 3D LGE with wideband inversion only. Comparison of
      3D and 2D LGE images demonstrated improved spatial resolution of the heart using
      3D LGE. CONCLUSION: Increased bandwidth of the inversion and excitation pulses
      can significantly reduce image artifacts associated with ICDs. Our modified
      wideband 3D LGE protocol can be readily used for imaging patients with ICDs given
      appropriate safety guidelines are followed.

PMID- 25772156
TI  - Disorder in milk proteins: structure, functional disorder, and biocidal
      potentials of lactoperoxidase.
AB  - This article continues a series of reviews on the abundance and roles of
      intrinsic disorder in milk proteins. Besides caseins, which are the major
      proteinaceous constituents of any milk that can be isolated by isoelectric
      precipitation, milk contains a set of soluble whey proteins, such as beta
      lactoglobulin, alpha-lactalbumin, serum albumin, immunoglobulins, lactoferrin,
      lactoperoxidase, glycomacropeptide, and proteose peptone (the last two are
      soluble casein derivatives). Lactoferrin and lactoperoxidase (LPO) are known to
      possess prominent biocidal activity, serving as efficient antibiotics and
      antiviral agents against a wide spectrum of bacteria, fungi, and viruses. LPO is
      a heme-containing peroxidase expressed as preproprotein. The mature protein has a
      single catalytic domain, structure of which is known for a protein isolated from
      several species. Functionally, LPO is a crucial component of the LPO system that
      includes LPO, hydrogen peroxide (H2O2), and thiocyanate (SCN(-)), being a well
      studied, naturally occurring antimicrobial system in milk that is effective
      against many microorganisms and some viruses. Although various aspects of LPO
      structure and function are rather well studied and were subjects of several
      recent reviews, the abundance and potential functional roles of intrinsically
      disordered regions in this protein have never being addressed as of yet. The
      major goal of this article is to fill this gap and to show how intrinsic disorder
      is encoded in the amino acid sequence of LPO, and how intrinsic disorder is
      related to functions of this important milk protein. 

PMID- 25772154
TI  - Carbon monoxide pollution and neurodevelopment: A public health concern.
AB  - Although an association between air pollution and adverse systemic health effects
      has been known for years, the effect of pollutants on neurodevelopment has been
      underappreciated. Recent evidence suggests a possible link between air pollution
      and neurocognitive impairment and behavioral disorders in children, however, the
      exact nature of this relationship remains poorly understood. Infants and children
      are uniquely vulnerable due to the potential for exposure in both the fetal and
      postnatal environments during critical periods in development. Carbon monoxide
      (CO), a common component of indoor and outdoor air pollution, can cross the
      placenta to gain access to the fetal circulation and the developing brain. Thus,
      CO is of particular interest as a known neurotoxin and a potential public health
      threat. Here we review overt CO toxicity and the policies regulating CO exposure,
      detail the evidence suggesting a potential link between CO-associated ambient air
      pollution, tobacco smoke, and learning and behavioral abnormalities in children,
      describe the effects of subclinical CO exposure on the brain during development,
      and provide mechanistic insight into a potential connection between CO exposure
      and neurodevelopmental outcome. CO can disrupt a number of critical processes in
      the developing brain, providing a better understanding of how this specific
      neurotoxin may impair neurodevelopment. However, further investigation is needed
      to better define the effects of perinatal CO exposure on the immature brain.
      Current policies regarding CO standards were established based on evidence of
      cardiovascular risk in adults with pre-existing comorbidities. Thus, recent and
      emerging data highlighted in this review regarding CO exposure in the fetus and
      developing child may be important to consider when the standards and guidelines
      are evaluated and revised in the future. 

PMID- 25772157
TI  - Integrase interactor 1 in health and disease.
AB  - Integrase interactor 1 (INI1/hSNF5) is a core component of the SWI/SNF chromatin
      remodeling complex that alters the structure of chromatin in order to facilitate
      DNA-dependent cellular processes like transcription, replication, and repair.
      Integrase interactor 1 (INI1/hSNF5) is a core component of the SWI/SNF chromatin
      remodeling complex that alters the structure of chromatin in order to facilitate
      DNA-dependent cellular processes like transcription, replication, and repair.
      INI1/hSNF5 plays an important role in a variety of cellular processes.
      Inactivation of the Snf5 gene in mice leads to embryonic lethality suggesting a
      critical role for INI1/hSNF5 in cellular function, viability, and development.
      Biallelic loss-of-function of INI1/hSNF5 leads to certain cancers, most
      frequently rhabdoid tumors, demonstrating that INI1/hSNF5 is a tumor suppressor
      gene. INI1/hSNF5 regulates several essential steps in the propagation of the HIV
      1 virus within the host cell, particularly HIV-1 integration. The mode of
      function of INI1/hSNF5 is only beginning to be understood. Given its importance
      in the normal functioning of the cell and its association with two diseases with
      high morbidity and mortality rates, it is imperative that the functions of this
      protein is delineated in greater detail in order to develop therapeutic
      interventions in certain cancers and AIDS. In this review, I have summarized the
      literature of published results on INI1/hSNF5 with emphasis on its molecular
      organization, role in different cellular pathways and involvement in AIDS and
      cancer. 

PMID- 25772159
TI  - Marr and reductionism.
AB  - David Marr's three-level method for completely understanding a cognitive system
      and the importance he attaches to the computational level are so familiar as to
      scarcely need repeating. Fewer seem to recognize that Marr defends his famous
      method by criticizing the "reductionistic approach." This sets up a more
      interesting relationship between Marr and reductionism than is usually
      acknowledged. I argue that Marr was correct in his criticism of the reductionists
      of his time-they were only describing (cellular activity), not explaining
      (cognitive functions). But a careful metascientific account of reductionistic
      neuroscience over the past two decades reveals that Marr's criticisms no longer
      have force. Contemporary neuroscience now explains cognition directly, although
      in a fashion-causal-mechanistically-quite different than Marr recommended. So
      while Marr was correct to reject the reductionism of his day and offer an
      alternative method for genuinely explaining cognition, contemporary cognitive
      scientists now owe us a new defense of Marr's famous method and the advantages of
      its explanations over the type now pursued successfully in current reductionist
      neuroscience. There are familiar reasons for thinking that this debt will not be
      paid easily. 

PMID- 25772160
TI  - Role of the surgeon in non-accidental trauma.
AB  - Non-accidental trauma (NAT) represents a significant cause of morbidity and
      mortality in the pediatric population. The management of these patients often
      involves many care providers including the surgeon. Victims of NAT often present
      with multiple injuries and as such should be treated as trauma patients with
      complete trauma evaluation including primary, secondary and tertiary surveys.
      Common injury patterns in NAT include extremity fractures, closed head injury and
      intra-abdominal injury. Brain imaging is of importance to rule out acute or sub
      acute intracranial hemorrhage. Children under the age of 5 years with acute
      intracranial pathology should also be evaluated by an ophthalmologist to rule out
      retinal hemorrhages, which are considered pathognomonic for child abuse from
      violent shaking. In instances when abdominal injury is suspected, prompt
      evaluation by a surgeon is recommended along with CT imaging. Finding of
      extremity fractures should prompt evaluation by an orthopedic surgeon. At our
      institution, all patients with suspected NAT are admitted to the pediatric
      surgery service for complete evaluation and management. We encourage other
      pediatric trauma centers to employ a similar approach so that these complicated
      patients are managed safely and effectively. 

PMID- 25772161
TI  - Does percutaneous internal ring suturing contain risk of ilioinguinal nerve
      entrapment?
AB  - PURPOSE: In this study, we aim to assess the alteration of IIN functions in
      children with inguinal hernias operated on using open or 'percutaneous internal
      ring suturing' (PIRS). METHODS: This study was based on a prospective clinical
      trial of 60 pediatric patients. They were operated on using PIRS or conventional
      open hernia repair technique. Group 1 included 35 patients who were treated with
      PIRS technique. Group 2 included 22 patients who underwent a conventional open
      hernia repair. The ilioinguinal nerve stimuli in both the operational and non
      operational areas were evaluated in patients with peripheral EMG for possible
      ilioinguinal nerve damage on the hernia side before the operation and to
      reevaluate ilioinguinal nerve function in the third postoperative week. RESULT:
      In Group 1, 19 cases underwent a preoperative EMG examination and in 35 cases,
      EMG examination was obtained postoperatively. Pre- and postoperative EMG results
      were normal in all cases in Group 1 on both the operational and non-operational
      sides. In Group 2, 15 preoperative and 25 postoperative EMG examinations were
      obtained. In Group 2, only one case with a right inguinal hernia who had normal
      preoperative EMG results showed no IIN response in a postoperative EMG evaluation
      obtained in the third postoperative week, with a normal left-side response. The
      EMG was repeated at the three-month postoperative third mark and revealed the
      same result. In a six-year-old female case, there was a negative EMG response on
      the non-operative side both pre- and postoperatively.

PMID- 25772162
TI  - Re. "Are paediatric operations evidence based?".

PMID- 25772163
TI  - Use of trans-labial ultrasound in the diagnosis of female urethral diverticula: A
      diagnostic option to be strongly considered.
AB  - AIM: To demonstrate effectiveness of trans-labial ultrasound (TL-US) in the
      evaluation of female urethral diverticula (UD). METHODS: In the study period, 20
      UD were diagnosed and treated. All data on demographic characteristics,
      presenting symptoms, physical examination findings, diagnostic and operative
      procedures, were considered. Patients were referred to TL-US for diverticular
      evaluation, using a 2D 7.5-MHz endfire probe. For each UD, size, complexity,
      echogenicity content, and presence of diverticular neck were considered. Follow
      up controls were carried out at 1, 6 and 12 months after surgery, to evaluate
      outcome and need for further intervention. RESULTS: Mean patient age was 46 years
      (range, 35-55 years) and mean parity was 1 (range, 0-3). The principal symptoms
      associated with the diverticular mass was dysuria (25%). In all evaluated cases,
      UD was single (simple in 15 cases and complex in 5). The mean size of the
      diverticula was 28 mm (range, 8-50 mm). Nineteen diverticula were diagnosed on TL
      US, and urethrocystoscopy was carried out for confirmation. Treatment consisted
      of diverticulectomy. At 1-, 6- and 12-month follow up after surgery, TL-US showed
      no recurrence of UD in any of the patients. CONCLUSIONS: TL-US is a valid, mini
      invasive and reproducible method to diagnose UD.

PMID- 25772164
TI  - Intraneuronal accumulation of misfolded tau protein induces overexpression of
      Hsp27 in activated astrocytes.
AB  - Accumulation of misfolded forms of microtubule associated, neuronal protein tau
      causes neurofibrillary degeneration typical of Alzheimer's disease and other
      tauopathies. This process is accompanied by elevated cellular stress and
      concomitant deregulation of heat-shock proteins. We used a transgenic rat model
      of tauopathy to study involvement of heat shock protein 27 (Hsp27) in the process
      of neurofibrillary degeneration, its cell type specific expression and
      correlation with the amount of insoluble tau protein aggregates. The expression
      of Hsp27-mRNA is more than doubled and levels of Hsp27 protein tripled in aged
      transgenic animals with tau pathology. The data revealed a strong positive and
      highly significant correlation between Hsp27-mRNA and amount of sarkosyl
      insoluble tau. Interestingly, intracellular accumulation of insoluble misfolded
      tau protein in neurons was associated with overexpression of Hsp27 almost
      exclusively in reactive astrocytes, not in neurons. The topological dissociation
      of neuronally expressed pathological tau and the induction of astrocytic Hsp27,
      GFAP, and Vimentin along with up-regulation of microglia specific markers such as
      CD18, CD68 and C3 point to cooperation of astrocytes, microglia and neurons in
      response to intra-neuronal accumulation of insoluble tau. Our data suggest that
      over expression of Hsp27 represents a part of microglia-mediated astrocytic
      response mechanism in the process of neurofibrillary degeneration, which is not
      necessarily associated with neuroprotection and which in contrary may accelerate
      neurodegeneration in late stage of the disease. This phenomenon should be
      considered during development of disease modifying strategies for treatment of
      tauopathies and AD via regulation of activity of Hsp27. 

PMID- 25772165
TI  - Nr0b1 is a negative regulator of Zscan4c in mouse embryonic stem cells.
AB  - Nuclear receptor subfamily 0, group B, member 1 (Nr0b1, also known as Dax1) is
      regarded as an important component of the transcription factor network that
      governs pluripotency in mouse embryonic stem (ES) cells. Here we generated
      inducible knockout ES cells for Nr0b1 using the Cre-loxP system and analyzed its
      precise function. We succeeded in establishing the Nr0b1-null ES cells and
      confirmed their pluripotency by showing their contribution to chimeric embryos.
      However, they proliferated slowly with over-expression of 2-cell stage specific
      transcripts including Zscan4c, which is known to be involved in telomere
      elongation in ES cells. We revealed that over-expression of Zscan4c prevents
      normal self-renewal by inducing arrest at G2 phase followed by cell death and
      that Nr0b1 directly represses the Zscan4c promoter. These data indicated that
      Nr0b1 is not essential to maintain pluripotency but is involved in the proper
      activation of 2-cell specific transcripts for self-renewal. 

PMID- 25772166
TI  - Temporal processing characteristics of the Ponzo illusion.
AB  - Many visual illusions result from assumptions of our visual system that are based
      on its long-term adaptation to our visual environment. Thus, visual illusions
      provide the opportunity to identify and learn about these fundamental
      assumptions. In this paper, we investigate the Ponzo illusion. Although many
      previous studies researched visual processing of the Ponzo illusion, only very
      few considered temporal processing aspects. However, it is well known that our
      visual percept is modulated by temporal factors. First, we used the Ponzo
      illusion as prime in a response priming task to test whether it modulates
      subsequent responses to the longer (or shorter) of two target bars. Second, we
      used the same stimuli in a perceptual task to test whether the Ponzo illusion is
      effective for very short presentation times (12 ms). We observed considerable
      priming effects that were of similar magnitude as those of a control condition.
      Moreover, the variations in the priming effects as a function of prime-target
      stimulus-onset asynchrony were very similar to that of the control condition.
      However, when analyzing priming effects as a function of participants' response
      speed, effects for the Ponzo illusion increased in slower responses. We conclude
      that although the illusion is established rapidly within the visual system, the
      full integration of context information is based on more time-consuming and later
      visual processing. 

PMID- 25772167
TI  - Ameliorating effects of traditional Chinese medicine on lipopolysaccharide 
      induced microcirculatory disturbances and organ injury.
AB  - Gram-negative bacteria are one of the major pathogens associated with severe
      sepsis and septic shock. LPS is a component of the outer membrane of gram
      negative bacteria, which causes a systemic, uncontrolled inflammatory response in
      infected subjects. In microcirculation it manifests multiple insults, including
      leukocyte and platelet adhesion, ROS and protease overproduction, mast cell
      degranulation, endothelium hyperpermeabilty, hemorrhage, and microthrombi
      formation, ultimately results in multiorgan dysfunction, DIC, refractory shock
      and even death. TCM has been used in China, Korea, Japan and other Asian
      countries for treatment of a wide range of diseases. In China, the usage of
      compound traditional preparation to treat inflammation-related diseases dates
      back to the Han Dynasty and the medical formulary had been developed thousands of
      years before, which recorded a great number of classical prescriptions for
      treatment with infectious diseases. This review will summarize the up to date
      works with respect to the ameliorating effects of compound and single traditional
      Chinese medicine and active components on LPS-induced inflammation, including
      clinical trial and experimental studies regarding multiorgan injury and
      underlying mechanisms.

PMID- 25772168
TI  - CCL2-CCR2 Signaling in Disease Pathogenesis.
AB  - The role of chemokines and their receptors in controlling several physiological
      and pathological processes has only become evident in the last couple of years.
      From a sole function of chemo-attraction, our view on chemokine receptor
      activation has switched to the regulation of pleiotropic signaling pathways
      influencing numerous molecular and cellular processes. The large number of
      chemokines and receptors and hence possible combinations of chemokine-chemokine
      receptor interactions, as well as the expression profiles of chemokines and
      chemokine receptors within particular cell types, has contributed to the
      complexity of chemokine receptor signaling as we see it today. The chemokine CCL2
      and its main chemokine receptor CCR2 have been implicated in the pathogenesis of
      several different disease processes, including vascular permeability and
      attraction of immune cells during metastasis, a number of different neurological
      disorders, autoimmune disease, obesity, and atherosclerosis. Here we review
      recent findings on the role of the CCL2-CCR2 axis in the regulation of these
      diseases. We believe that research has only gained a first glimpse of what
      chemokines can control and what the underlying mechanisms are. There is certainly
      more to be found that will - with high certainty - have strong implications for
      clinical applications in the near future. 

PMID- 25772169
TI  - Curcumin targets in inflammation and cancer.
AB  - Curcumin (1,7-bis(4-hydroxy-3-methoxyphenyl)-1,6-heptadiene-3,5-dione) is
      commonly used as a spice, food additive or dietary pigment. Accumulating evidence
      suggests that curcumin has several pharmacologic effects, including anti
      inflammatory, anti-oxidant and anti-cancer activities. The molecular mechanisms
      underlying the targets of curcumin are diverse and involve combinations of
      multiple signaling pathways, including NF-kappaB and STAT3 signaling. Thus,
      curcumin is one of the most promising phytochemicals that target various cancers
      and inflammation-mediated diseases. Clinical trials have been ongoing or
      completed for various cancers, including breast, pancreatic and colorectal
      cancers, and multiple myeloma. In this review, the molecular mechanisms and the
      issue of bioavailability are mainly discussed. 

PMID- 25772171
TI  - IL-1 as a target in inflammation.
AB  - Inflammation is a protective response to eliminate cytotoxic agents and
      pathogens. Various factors are thought to be involved in the pathological changes
      in tissues caused by inflammation. Interleukin 1, an inflammatory cytokine, is
      thought to have diverse physiological functions and to play an important role in
      inflammatory disease. In this review, we discuss interleukin-1 as a target of
      inflammatory disease.

PMID- 25772170
TI  - Eph as a target in inflammation.
AB  - Evidence to show that the Eph/ephrin system is involved in inflammation induced
      by infection, injury, inflammatory diseases, and atherosclerosis has been
      increased. Although the roles of the Eph/ephrin system in both neural and
      vascular development as well as cell motility are well documented, its
      involvement in inflammatory processes has not yet been elucidated in detail.
      Moreover, the soluble form of artificially oligomerized or dimerized Fc-fused
      ephrin-A1 has been widely used in in vitro and/or in vivo studies to activate the
      EphA receptors, whereas its physiological functions as a membrane-anchored
      protein remain largely unknown. Recent studies using clinical samples reported
      that the overexpression of Ephs and ephrins in some tumors such as hepatocellular
      carcinoma positively correlated with both malignancy of tumors and the poor
      prognosis of cancer patients. However, the molecular mechanisms underlying
      malignancy of tumors are not fully understood. The author herein summarizes the
      molecular mechanisms of the Eph/ephrin system involved in the immune system and
      inflammatory processes. Especially, the author focuses on inflammation-induced
      physiological changes in vascular endothelial cells leading to vascular hyper
      permeability and described them in this review. The author also introduces those
      that contribute to ephrin-A1-mediated lung metastasis. 

PMID- 25772172
TI  - IL-6 as a target in inflammation.
AB  - Interleukin-6 (IL-6) has a unique feature of its own signaling pathway. IL-6 can
      act on various types of cells because there are abundant amounts of soluble IL-6
      receptor in peripheral blood and can mediate signaling into cells. IL-6
      participates in a broad spectrum of biological events, such as immune responses,
      hematopoiesis, and acute-phase reactions. In contrast, overproduction of IL-6 has
      been implicated in the pathogenesis of a variety of diseases, including several
      chronic inflammatory diseases. Future studies to clarify the molecular mechanisms
      of IL-6 functions as well as studies in which inhibitors of IL-6 signaling are
      used should provide information critical to a better understanding of the
      molecular mechanisms of diseases and the development of new therapeutic methods.

PMID- 25772173
TI  - Metalloproteinases: potential therapeutic targets for rheumatoid arthritis.
AB  - In different inflammatory diseases, many metalloproteinases are over expressed
      and thought to promote progression of the disease. Understanding roles of these
      enzymes in disease progression as well as in normal homeostasis is crucial to
      identify target enzymes for the disease. Rheumatoid arthritis (RA) is one of the
      autoimmune inflammatory diseases in which around 1-2 % of the world populations
      are suffered from. Roles of metalloproteinases are well documented in RA, but so
      far none of them is proposed to be a target enzyme. However, there are at least
      three enzymes that can potentially be molecular targets to inhibit progression of
      RA. Understanding roles of these enzymes in more detail and developing highly
      selective inhibitors to these enzymes would be essential for novel
      antimetalloproteinase therapies in future. 

PMID- 25772174
TI  - Metformin and Inflammation: Its Potential Beyond Glucose-lowering Effect.
AB  - Metformin is an oral hypoglycemic agent which is most widely used as first-line
      therapy for type 2 diabetes. Metformin improves hyperglycemia by suppressing
      hepatic glucose production and increasing glucose uptake in muscle. Metformin
      also has been shown to reduce cardiovascular events in randomized controlled
      trials; however, the underlying mechanism remains to be established. Recent
      preclinical and clinical studies have suggested that metformin not only improves
      chronic inflammation through the improvement of metabolic parameters such as
      hyperglycemia, insulin resistance and atherogenic dyslipidemia, but also has a
      direct anti-inflammatory action. Studies have suggested that metformin suppresses
      inflammatory response by inhibition of nuclear factor kappaB (NFkappaB) via AMP
      activated protein kinase (AMPK)-dependent and independent pathways. This review
      summarizes the basic and clinical evidence of the anti-inflammatory action of
      metformin and discusses its clinical implication. 

PMID- 25772175
TI  - One Special Question to Start with: Can HIF/NFkB be a Target in Inflammation?
AB  - Hypoxia and Inflammation are strictly interconnected with important consequences
      at clinical and therapeutic level. While cell and tissue damage due to acute
      hypoxia mostly leads to cell necrosis, in chronic hypoxia, cells that are located
      closer to vessels are able to survive adapting their phenotype through the
      expression of a number of genes, including proinflammatory receptors for
      alarmins. These receptors are activated by alarmins released by necrotic cells
      and generate signals for master transcription factors such as NFkB, AP1, etc.
      which control hundreds of genes for innate immunity and damage repair. Clinical
      consequences of chronic inflammatory reparative response activation include cell
      and tissue remodeling, damage in the primary site and, the systemic involvement
      of distant organs and tissues. Thus every time a tissue environment becomes
      stably hypoxic, inflammation can be activated followed by chronic damage and cell
      death or repair with vessel proliferation and fibrosis. This pathway can occur in
      cancer, myocardial infarction and stroke, diabetes, obesity, neurodegenerative
      diseases, chronic and autoimmune diseases and age-related diseases.
      Interestingly, proinflammatory gene expression can be observed earlier in hypoxic
      tissue cells and, in addition, in activated resident or recruited leukocytes.
      Herewith, the reciprocal relationships between hypoxia and inflammation will be
      shortly reviewed to underline the possible therapeutic targets to control hypoxia
      related inflammation in a number of epidemiologically important human diseases
      and conditions. 

PMID- 25772176
TI  - Resveratrol Targets in Inflammation.
AB  - Resveratrol, a constituent of grapes and various other plants, has been an
      attractive compound for biomedical studies because moderate long-term drinking of
      red wine is associated with a reduced risk of lifestyle-related diseases, such as
      cardiovascular diseases and cancer. Resveratrol is as a phytoalexin,
      cyclooxygenase (COX) suppressor, and an activator of peroxisome
      proliferatoractivated receptor (PPAR) and SIRT1. As a major phytoalexin,
      resveratrol is produced by plants in response to various environmental stresses,
      such as pathogens and ultraviolet (UV) radiation, and promotes resistance to
      these stresses. A similar active ingredient, salicylic acid (SA), is also
      produced by plants. Aspirin, acetylated SA, is a major nonsteroidal anti
      inflammatory drug (NSAID) because it inhibits COX activity in humans. The
      jasmonic acid (JA) pathway in plants and the COX pathway in humans are both
      defense systems against environmental stresses and involve lipid mediators
      derived from phospholipids. We can hypothesize that there is a molecular basis
      for the mutually beneficial relationship between plants and humans, which is
      important for understanding the mode of action of resveratrol in inflammation.
      Here we provide a review of the studies on resveratrol, especially with respect
      to the role of COX and PPAR in inflammation. 

PMID- 25772177
TI  - S100A9 as a Pharmacological Target Molecule in Inflammation and Cancer.
AB  - Upon tissue injury and infection both stressed and dying cells can release
      proteins that normally reside inside the cells. Some of the released proteins
      become ligands of various cell surface receptors expressed by local cells and
      such proteins are denoted as damage associated molecular patterns (DAMPs).
      Binding of some DAMPs to certain cell surface receptors induces signals emanating
      in the production of pro-inflammatory cytokines, ultimately leading to an
      inflammatory response. Our laboratory is interested in the S100A9 protein, a bona
      fide DAMP protein. This protein normally resides inside monocytes and neutrophils
      and in these cells it forms heterodimers with the S100A8 protein. The S100A8/A9
      heterodimer is released in large amounts during several types of inflammatory
      disease and is currently used clinically as a biomarker in some diseases. The
      fact that several different proinflammatory functions have been ascribed to this
      protein makes it a potential target for the development of small molecule
      inhibitors. We have developed several such inhibitors, some of which are already
      in phase III clinical development. This review describes our efforts to
      investigate the biological functions of the S100A9 protein as well as our ongoing
      efforts of developing second-generation, more specific, small molecule inhibitors
      of its pro-inflammatory functions. 

PMID- 25772178
TI  - TNF as a Target of Inflammation in Rheumatoid Arthritis.
AB  - Anti-Tumor Necrosis Factor (TNF) agents were the first molecular targeting drugs
      developed for the treatment of rheumatoid arthritis (RA). Anti-TNF agents improve
      the clinical picture of severe RA patients, inhibit joint destruction and improve
      quality of life. In the 15 years since their introduction, they have become the
      preferred drug therapy for management of RA. The success of anti-TNF agents in
      the treatment of RA has resulted in the development of many drugs for other
      inflammatory diseases using the same molecular targeting concept. However, many
      unresolved issues surround the use of anti-TNF agents, including the risk for
      infection, primary non-responders, secondary loss of efficacy and
      pharmacoeconomical issues. This review focuses on the multifaceted impact of anti
      TNF agents in the treatment of RA. 

PMID- 25772179
TI  - VEGF-VEGFR System as a Target for Suppressing Inflammation and other Diseases.
AB  - The vascular endothelial growth factor (VEGF)-VEGF receptor (R) system is deeply
      involved in angiogenesis and lymphangiogenesis. VEGFR1/ Fms-like tyrosine kinase
      1 (Flt-1) and VEGFR2 are significantly expressed in vascular endothelial cells,
      where they transfer proangiogenic signals. Particularly, VEGFR2 has strong
      tyrosine kinase activity; thus, the major and direct angiogenic signals are
      generated from VEGFR2. VEGFR3 is specifically expressed in lymphatic endothelial
      cells, generating the main signal for lymphangiogenesis. In addition, VEGFR1 is
      wellexpressed on the membrane of macrophage lineage cells such as monocytes,
      transducing an important signal for the migration and cytokine/chemokine
      production of these cells. This VEGFR1-macrophage axis stimulates seemingly non
      inflammatory and inflammatory responses in various tissues and promotes a variety
      of diseases such as tumor growth via proangiogenesis, tumor metastasis,
      lymphangiogenesis, arthritis, and atherosclerosis. This axis is also important
      for the physiological recovery systems like bone marrow reconstitution and wound
      healing. VEGFR1 expresses two forms of mRNA: one for the full-length VEGFR1/Flt-1
      receptor with tyrosine kinase; the other for a soluble form carrying only the
      ligand-binding region (sFlt-1/soluble VEGFR1) that functions as a decoy receptor
      by trapping its ligands VEGF-A, PlGF, and VEGF-B. Therefore, the VEGFR1-dependent
      inflammatory and non-inflammatory reactions are also regulated by a balance of
      gene expression between full-length and soluble forms of VEGFR1/Flt-1. Taken
      together, these findings suggest that VEGF-VEGFR signal is an important target
      for suppressing various diseases including inflammation. 

PMID- 25772180
TI  - Vitamin-mediated immune regulation in the development of inflammatory diseases.
AB  - Mucosal tissues and especially the intestine are constantly exposed to abundant
      non-self materials yet simultaneously establish immune homeostasis to prevent
      excessive inflammatory responses. The maintenance of intestinal homeostasis is
      achieved by a harmonized immune network mediated by endogenous factors (e.g.,
      cytokines and chemokines) and exogenous factors (e.g., commensal bacteria and
      dietary matter). Specifically, vitamins from such exogenous sources function
      immunologically in the control of homeostatic immune responses; thus, their
      deficient or excessive intake is associated with the development of inflammatory
      diseases. The focus of this review is the immunologic functions of vitamins B3,
      B9, A, and D in the regulation and development of inflammation. 

PMID- 25772181
TI  - Adiponectin as a Target in Obesity-related Inflammatory State.
AB  - Accumulating evidence indicates that low grade inflammation is closely associated
      with obesity-related disorders including type 2 diabetes, hypertension and
      atherosclerosis. Adiponectin is a fat-derived plasma protein with anti
      inflammatory functions. Circulating levels of adiponectin are decreased in obese
      states, and these conditions are broadly associated with various obesity-related
      diseases. Furthermore, adiponectin has direct protective functions against
      cardiovascular disease, cerebrovascular disease, non-alcoholic steatohepatitis
      (NASH) and chronic kidney disease (CKD). In this review, we will focus on the
      protective functions of adiponectin against these obesity-related diseases from
      the view point of its anti-inflammatory properties. 

PMID- 25772182
TI  - Prognostic factors and patterns of relapse in ewing sarcoma patients treated with
      chemotherapy and r0 resection.
AB  - PURPOSE: To identify prognostic factors and patterns of relapse for patients with
      Ewing sarcoma who underwent chemotherapy and R0 resection without radiation
      therapy (RT). METHODS AND MATERIALS: We reviewed the medical records of patients
      who underwent surgical resection at our institution between 2000 and 2013 for an
      initial diagnosis of Ewing sarcoma. The associations of demographic and clinical
      factors with local control (LC) and patient outcome were determined by Cox
      regression. Time to events was measured from the time of surgery. Survival curves
      were estimated by the Kaplan-Meier method and compared by the log-rank test.
      RESULTS: A total of 66 patients (median age 19 years, range 4-55 years) met the
      study criteria. The median follow-up was 5.6 years for living patients. In 43
      patients (65%) for whom imaging studies were available, the median tumor volume
      reduction was 73%, and at least partial response by Response Evaluation Criteria
      in Solid Tumors was achieved in 17 patients (40%). At 5 years, LC was 78%,
      progression-free survival (PFS) was 59%, and overall survival (OS) was 65%. Poor
      histologic response (necrosis <=95%) was an independent predictor of LC (hazard
      ratio [HR] 6.8, P=.004), PFS (HR 5.2, P=.008), and OS (HR 5.0, P=.008).
      Metastasis on presentation was also an independent predictor of LC (HR 6.3,
      P=.011), PFS (HR 6.8, P=.002), and OS (HR 6.7, P=.002). Radiologic partial
      response was a predictor of PFS (HR 0.26, P=.012), and postchemotherapy tumor
      volume was associated with OS (HR 1.06, P=.015). All deaths were preceded by
      distant relapse. Of the 8 initial local-only relapses, 5 (63%) were soon followed
      by distant relapse. Predictors of poor postrecurrence survival were time to
      recurrence <1 year (HR 11.5, P=.002) and simultaneous local and distant relapse
      (HR 16.8, P=.001). CONCLUSIONS: Histologic and radiologic response to
      chemotherapy were independent predictors of outcome. Additional study is needed
      to determine the role of adjuvant radiation therapy for patients who have poor
      histologic response after R0 resection.

PMID- 25772183
TI  - External beam radiation therapy and abiraterone in men with localized prostate
      cancer: safety and effect on tissue androgens.
AB  - PURPOSE: Optimizing androgen suppression may provide better control of localized
      prostate cancer (PCa). Numerous trials have supported the benefit of combining
      androgen deprivation therapy with definitive radiation therapy in men with
      locally advanced or high-grade disease. Addition of abiraterone to luteinizing
      hormone-releasing hormone agonist (LHRHa) with radiation has not been reported.
      We examined the safety of this combination as well as its impact on androgen
      suppression. METHODS AND MATERIALS: A prospective, phase 2 study was conducted in
      men with localized PCa treated with 6 months of neoadjuvant and concurrent
      abiraterone with LHRHa and radiation. Duration of adjuvant LHRHa was at the
      discretion of the treating clinician. Prostate biopsy assays were obtained prior
      to the start of therapy and prior to radiation. Sera and tissue androgen levels
      were measured by liquid chromatography-tandem mass spectrometry. RESULTS: A total
      of 22 men with intermediate- (n=3) and high-risk PCa (n=19) received study
      therapy. Sixteen men completed the intended course of abiraterone, and 19 men
      completed planned radiation to 77.4 to 81 Gy. Radiation to pelvic nodes was
      administered in 20 men. The following grade 3 toxicities were reported:
      lymphopenia (14 patients), fatigue (1 patient), transaminitis (2 patients),
      hypertension (2 patients), and hypokalemia (1 patient). There were no grade 4
      toxicities. All 21 men who complied with at least 3 months of abiraterone therapy
      had a preradiation prostate-specific antigen (PSA) concentration nadir of <0.3
      ng/mL. Median levels of tissue androgen downstream of CYP17A were significantly
      suppressed after treatment with abiraterone, and upstream steroids were
      increased. At median follow-up of 21 months (range: 3-37 months), only 1 patient
      (who had discontinued abiraterone at 3 months) had biochemical relapse.
      CONCLUSIONS: Addition of abiraterone to LHRHa with radiation is safe and achieves
      effective prostatic androgen suppression. Preliminary analysis of the clinical
      data is also promising, with excellent PSA nadir and no relapse to date in this
      high-risk population.

PMID- 25772184
TI  - Results of neoadjuvant short-course radiation therapy followed by transanal
      endoscopic microsurgery for t1-t2 n0 extraperitoneal rectal cancer.
AB  - PURPOSE: This study was undertaken to assess the short-term outcomes of
      neoadjuvant short-course radiation therapy (SCRT) followed by transanal
      endoscopic microsurgery (TEM) for T1-T2 N0 extraperitoneal rectal cancer. Recent
      studies suggest that neoadjuvant radiation therapy followed by TEM is safe and
      has results similar to those with abdominal rectal resection for the treatment of
      extraperitoneal early rectal cancer. METHODS AND MATERIALS: We planned a
      prospective pilot study including 25 consecutive patients with extraperitoneal T1
      T2 N0 M0 rectal adenocarcinoma undergoing SCRT followed by TEM 4 to 10 weeks
      later (SCRT-TEM). Safety, efficacy, and acceptability of this treatment modality
      were compared with historical groups of patients with similar rectal cancer stage
      and treated with long-course radiation therapy (LCRT) followed by TEM (LCRT-TEM),
      TEM alone, or laparoscopic rectal resection with total mesorectal excision (TME)
      at our institution. RESULTS: The study was interrupted after 14 patients
      underwent SCRT of 25 Gy in 5 fractions followed by TEM. Median time between SCRT
      and TEM was 7 weeks (range: 4-10 weeks). Although no preoperative complications
      occurred, rectal suture dehiscence was observed in 7 patients (50%) at 4 weeks
      follow-up, associated with an enterocutaneous fistula in the sacral area in 2
      cases. One patient required a colostomy. Quality of life at 1-month follow-up,
      according to European Organization for Research and Treatment of Cancer QLQ-C30
      survey score, was significantly worse in SCRT-TEM patients than in LCRT-TEM
      patients (P=.0277) or TEM patients (P=.0004), whereas no differences were
      observed with TME patients (P=.604). At a median follow-up of 10 months (range: 6
      26 months), we observed 1 (7%) local recurrence at 6 months that was treated with
      abdominoperineal resection. CONCLUSIONS: SCRT followed by TEM for T1-T2 N0 rectal
      cancer is burdened by a high rate of painful dehiscence of the suture line and
      enterocutaneous fistula, compared to TEM alone and TEM following LCRT, which
      forced us to stop the study.

PMID- 25772185
TI  - Reply to Lavi & Sapir (2015): floral colour and pollinator-mediated selection in
      Oncocyclus irises (Iridaceae).

PMID- 25772186
TI  - Adult onset limb-girdle muscular dystrophy - a recessive titinopathy masquerading
      as myositis.
AB  - Rarely, inflammation can be present in genetic myopathies, such as
      dysferlinopathies, facioscapulohumeral muscular dystrophy and GNE-myopathy
      (hereditary inclusion body myopathy). This may lead to erroneous initial
      diagnosis and unnecessary therapy which bear serious side effects. We report on
      an unusual case of mutations in the TTN gene presenting with inflammatory
      infiltrates in the muscle biopsy. Only after intensive immune-modulating
      therapies failed, a genetic myopathy was considered. Exome sequencing and search
      for mutated muscle protein-encoding genes disclosed compound heterozygous
      mutations in TTN: K26320T and A6135G. The parents carry one each of the
      mutations. Titinopathy could be considered also in patients presenting with
      inflammatory infiltrates resistant to therapy. 

PMID- 25772187
TI  - Is pushing the wall, the best known method for scapular winging, really the best?
      A Comparative analysis of various methods in neuromuscular disorders.
AB  - INTRODUCTION: 'Pushing the wall' has found acceptance in medical teachings. Other
      methods of scapular winging are less known. Comparative evaluation of the five
      available methods has not been undertaken. This study focuses on evaluation of
      the available methods in groups of neuromuscular disorders to select the most
      sensitive method and to characterize patterns of scapular winging. A survey of
      methods practiced by clinicians also forms a part of the study. MATERIALS AND
      METHODS: Prospective study. Part A: questionnaire based survey of clinicians to
      explore the preferred method of examination for scapular winging. Part B:
      comparative analysis of five methods of scapular winging in four categories of
      neuromuscular disorders [facioscapulohumeral muscular dystrophy (FSHD), limb
      girdle muscular dystrophy, dystrophinopathies and neurogenic disorders]. RESULTS
      AND CONCLUSIONS: Forward lowering of arms was the most sensitive method [100%].
      The use of this method in clinical teachings and routine bedside examination
      should be promoted. Pushing the wall was the most popular method, but was fourth
      in the sensitivity [60.41%]. Arm maneuvers can bring out winging, when it is not
      apparent at rest. FSHD patients had a unique combination of winging at rest,
      persistence of winging throughout the range of motion and elevation of scapulae.

PMID- 25772188
TI  - Dopaminergic denervation is not necessary to induce gait disorders in atypical
      parkinsonian syndrome.
AB  - BACKGROUND: Gait impairment is common in parkinsonian syndromes but not specific
      to striatonigral dysfunction. The relationship between the dopaminergic system
      and gait parameters is poorly understood. This cross-sectional study aimed to
      determine if gait measures are related to the striatal dopamine transporters
      distribution using [(123)I]FP-CIT SPECT in patients with parkinsonian syndromes.
      MATERIALS AND METHODS: Twenty-four patients with gait impairment and parkinsonian
      syndromes without Parkinson's disease (mean age: 73.6+/-8.2years) were included
      in this study. Gait analysis during single- and dual-task condition (walking and
      backwards counting) and [(123)I]FP-CIT SPECT were performed within 3months of
      each other. Patients were visually categorized as having normal (n=14) or
      abnormal (n=10) [(123)I]FP-CIT SPECT. In addition, a volume-of-interest-based
      analysis of uptake ratios (caudate and putamen) relative to the occipital cortex
      and a voxelwise analysis using SPM8 were also performed. RESULTS: Patients with
      parkinsonian syndromes and abnormal [(123)I]FP-CIT SPECT did not significantly
      differ in terms of spatiotemporal gait parameters from those with normal
      [(123)I]FP-CIT SPECT. Moreover, after correction for multiple comparisons, we did
      not observe any association between regional uptake ratio and spatiotemporal gait
      parameters for single and dual tasking. Finally, none of these parameters showed
      a significant association with voxelwise [(123)I]FP-CIT uptake. CONCLUSIONS:
      Dopaminergic denervation, as measured by [(123)I]FP-CIT SPECT, is not necessary
      to induce alterations of spatiotemporal gait parameters during single and dual
      task in patients presenting with atypical parkinsonian syndromes.

PMID- 25772190
TI  - Screening for High Blood Pressure in Adults During Ambulatory Nonprimary Care
      Visits: Opportunities to Improve Hypertension Recognition.
AB  - Visits with nonprimary care providers such as optometrists may be missed
      opportunities for the detection of high blood pressure (BP). For this study,
      normotensive adults with at least 12 months of health plan membership on January
      1, 2009 (n=1,075,522) were followed-up for high BP through March 14, 2011. Of
      111,996 patients with a BP measurement >=140/90 mm Hg, 82.7% were measured during
      primary care visits and 17.3% during nonprimary care visits. Individuals with a
      BP >=140/90 mm Hg measured during nonprimary care visits were older and more
      likely to be male and non-Hispanic white. The proportion of patients with follow
      up and false-positives were comparable between primary and nonprimary care. The
      main nonprimary care specialty to identify a first BP >=140/90 mm Hg was
      ophthalmology/optometry with 24.5% of all patients. Results suggest that
      expanding screening for hypertension to nonprimary care settings may improve the
      detection of hypertension.

PMID- 25772189
TI  - Photosensitivity of neurons enabled by cell-targeted gold nanoparticles.
AB  - Unmodified neurons can be directly stimulated with light to produce action
      potentials, but such techniques have lacked localization of the delivered light
      energy. Here we show that gold nanoparticles can be conjugated to high-avidity
      ligands for a variety of cellular targets. Once bound to a neuron, these
      particles transduce millisecond pulses of light into heat, which changes membrane
      capacitance, depolarizing the cell and eliciting action potentials. Compared to
      non-functionalized nanoparticles, ligand-conjugated nanoparticles highly resist
      convective washout and enable photothermal stimulation with lower delivered
      energy and resulting temperature increase. Ligands targeting three different
      membrane proteins were tested; all showed similar activity and washout
      resistance. This suggests that many types of ligands can be bound to
      nanoparticles, preserving ligand and nanoparticle function, and that many
      different cell phenotypes can be targeted by appropriate choice of ligand. The
      findings have applications as an alternative to optogenetics and potentially for
      therapies involving neuronal photostimulation.

PMID- 25772191
TI  - Essential fatty acid intake and serum fatty acid composition among adolescent
      girls in central Mozambique.
AB  - Many African diets are low in fat but are currently changing because of nutrition
      transition. We studied fat and fatty acid (FA) intake and the essential fatty
      acid (EFA) status of adolescent girls (aged 14-19 years, n 262) in Zambezia
      Province, central Mozambique. A cross-sectional study was carried out in a city
      as well as in the towns and rural villages of a coastal and an inland district.
      Dietary intake and FA sources were studied in a 24 h dietary recall. FA
      compositions of cholesteryl esters and phospholipids of non-fasting serum samples
      were analysed by GLC. Fat intake was low (13-18 % of energy) in all areas.
      Coconut and palm oil were the main sources of fat, and soyabean oil and maize
      were the main sources of PUFA. Compared to Food and Agriculture Organization/WHO
      2010 recommendations, intake of linoleic acid (LA, 18 : 2n-6) was inadequate in
      the coastal district, and intakes of n-3 PUFA were inadequate in all areas. FA
      compositions of serum lipids differed between areas. The proportions of LA tended
      to be highest in the city and lowest in the rural areas. The phospholipid mead
      (20 : 3n-9):arachidonic acid (20 : 4n-6) ratio did not indicate EFA
      insufficiency. LA proportions in phospholipids were low, but those of long-chain
      n-6 and n-3 PUFA were high in comparison with Western adolescents. To conclude,
      fat sources, FA intake and EFA status differed between adolescent girls living in
      different types of communities. Fat intake was low, but EFA insufficiency was not
      indicated. 

PMID- 25772192
TI  - Postsynaptic gephyrin clustering controls the development of adult-born granule
      cells in the olfactory bulb.
AB  - In adult rodent olfactory bulb, GABAergic signaling regulates migration,
      differentiation, and synaptic integration of newborn granule cells (GCs),
      migrating from the subventricular zone. Here we show that these effects depend on
      the formation of a postsynaptic scaffold organized by gephyrin-the main
      scaffolding protein of GABAergic synapses, which anchors receptors and signaling
      molecules to the postsynaptic density-and are regulated by the phosphorylation
      status of gephyrin. Using lentiviral vectors to selectively transfect adult-born
      GCs, we observed that overexpression of the phospho-deficient gephyrin mutant
      eGFP-gephyrin(S270A), which facilitates the formation of supernumerary GABAergic
      synapses in vitro, favors dendritic branching and the formation of transient
      GABAergic synapses on spines, identified by the presence of alpha2-GABAA Rs. In
      contrast, overexpression of the dominant-negative eGFP-gephyrin(L2B) (a chimera
      that is enzymatically active but clustering defective), curtailed dendritic
      growth, spine formation, and long-term survival of GCs, pointing to the essential
      role of gephyrin cluster formation for its function. We could exclude any
      gephyrin overexpression artifacts, as GCs infected with eGFP-gephyrin were
      comparable to those infected with eGFP alone. The opposite effects induced by the
      two gephyrin mutant constructs indicate that the gephyrin scaffold at GABAergic
      synapses orchestrates signaling cascades acting on the cytoskeleton to regulate
      neuronal growth and synapse formation. Specifically, gephyrin phosphorylation
      emerges as a novel mechanism regulating morphological differentiation and long
      term survival of adult-born olfactory bulb neurons.

PMID- 25772193
TI  - Comparison of Carisolv system vs traditional rotating instruments for caries
      removal in the primary dentition: A systematic review and meta-analysis.
AB  - OBJECTIVE: The purpose of this systematic review and meta-analysis was to
      evaluate the reliability of the Carisolv system with respect to drilling
      regarding the full removal of decayed hard tissues in primary dentition. A
      systematic review of the literature was conducted to identify controlled trails,
      randomized controlled trials and clinical trials that compared the Carisolv
      system to the traditional mechanical caries removal in the primary dentition.
      MATERIALS AND METHODS: The main relevant databases were searched: MEDLINE via
      PUBMED, Web of Science and SCOPUS. Complete caries removal, length of working
      time and need of local anesthesia were the outcomes evaluated. RESULTS: A total
      of 195 studies were identified and complete analysis of 28 studies was performed;
      finally, 10 papers were included. The trials included involved a total of 348
      patients for 532 treated teeth. There was no significant difference in terms of
      clinical efficacy between the Carisolv and the rotary instrument (z = 0.68, p =
      0.50), whereas the treatment with Carisolv was significantly longer in terms of
      time with respect to the rotary instruments (z = 10.49, p < 0.01). The chemo
      mechanical technique reduces the need for local anesthesia, with a difference
      between two types of treatment near to statistical significance (z = 1.91 p =
      0.06). CONCLUSIONS: This systematic review indicates that the clinical efficacy
      of chemo-mechanical removal with Carisolv seems as reliable as the rotary
      instruments. However, the results should be interpreted cautiously due to the
      heterogeneity among study designs and to the shortage of available data. Further
      large-scale, well-designed randomized controlled trials are needed.

PMID- 25772194
TI  - Complex spatiotemporal behavior in the photosensitive ferroin-bromate-4
      nitrophenol reaction.
AB  - Investigation illustrates that the bromate-4-nitrophenol reaction in a stirred
      batch reactor undergoes spontaneous oscillations under very broad initial
      reactant concentrations. The addition of ferroin has subtle influences on the
      nonlinear behavior, in which the frequency and total number of oscillations were
      greatly reduced at a low or high ferroin concentration, as opposed to the
      significant increase at a moderate ferroin concentration. Temporal oscillations
      with a modulating frequency were also observed in the ferroin-bromate-4
      nitrophenol system. In a capillary tube the ferroin-bromate-4-nitrophenol
      reaction generated propagating wave trains with various complex behaviors such as
      period-doubled intermittent propagation failure. Illumination was found to have a
      profound effect on the temporal oscillations in the bromate-4-nitrophenol
      reaction and on those long lasting wave activities. Spectroscopic studies were
      able to identify 1,4-benzoquinone, 2-bromo-1,4-benzoquinone, and 2-bromo-4
      nitrophenol as major components during the reaction. 

PMID- 25772195
TI  - Vending machine assessment methodology. A systematic review.
AB  - The nutritional quality of food and beverage products sold in vending machines
      has been implicated as a contributing factor to the development of an obesogenic
      food environment. How comprehensive, reliable, and valid are the current
      assessment tools for vending machines to support or refute these claims? A
      systematic review was conducted to summarize, compare, and evaluate the current
      methodologies and available tools for vending machine assessment. A total of 24
      relevant research studies published between 1981 and 2013 met inclusion criteria
      for this review. The methodological variables reviewed in this study include
      assessment tool type, study location, machine accessibility, product
      availability, healthfulness criteria, portion size, price, product promotion, and
      quality of scientific practice. There were wide variations in the depth of the
      assessment methodologies and product healthfulness criteria utilized among the
      reviewed studies. Of the reviewed studies, 39% evaluated machine accessibility,
      91% evaluated product availability, 96% established healthfulness criteria, 70%
      evaluated portion size, 48% evaluated price, 52% evaluated product promotion, and
      22% evaluated the quality of scientific practice. Of all reviewed articles, 87%
      reached conclusions that provided insight into the healthfulness of vended
      products and/or vending environment. Product healthfulness criteria and
      complexity for snack and beverage products was also found to be variable between
      the reviewed studies. These findings make it difficult to compare results between
      studies. A universal, valid, and reliable vending machine assessment tool that is
      comprehensive yet user-friendly is recommended.

PMID- 25772196
TI  - The satiating effects of eggs or cottage cheese are similar in healthy subjects
      despite differences in postprandial kinetics.
AB  - Studies have reported a better satiating effect of eggs when compared with common
      cereal-based breakfasts, an effect that can be attributed to their macronutrient
      composition. Our aim was to compare the satiating power of an omelette and
      cottage cheese, both being common food snacks with similar nutrient compositions
      (containing proteins and lipids) but in different food forms. Thirty healthy
      volunteers participated in a randomized crossover trial. On each test day, the
      subjects consumed one of the two snacks, both providing 1346 kJ, 26 g protein, 21
      g lipids, and 8 g lactose. The elapsed time between the snack and lunch request,
      their food intake at lunch, and their satiety scores were recorded. In a subgroup
      of 10 volunteers, blood was sampled to measure plasma metabolites and hormones.
      The two preloads were similar in terms of the time between the snack and a
      request for the buffet (167 +/- 8 min), energy intake at the buffet (3988 +/- 180
      kJ) and appetite ratings. Plasma amino acid and urea concentrations indicated a
      marked delay in kinetic delivery after the eggs compared with the cottage cheese.
      In contrast, glucose, triglycerides and cholesterol displayed similar profiles
      after the snack. GIP and insulin secretions increased significantly after the
      cottage cheese, while glucagon and GLP-1 secretions were delayed with the
      omelette. We conclude that despite important differences in protein kinetics and
      their subsequent effects on hormone secretion, eggs and cottage cheese had a
      similar satiating power. This strongly suggests that with dose of proteins that
      is compatible to supplement strategies, i.e. 20-30 g, a modulation of protein
      kinetics is ineffective in increasing satiety.

PMID- 25772197
TI  - Health behaviours and their facilitation under depletion conditions: the case of
      snacking.
AB  - INTRODUCTION: Previous research suggests that depletion (the state ensuing from
      self-control exertion) engenders lapses in health behaviours. The present study
      tested for that effect in relation to the health behaviour of limiting snacking,
      and investigated whether health goal-priming might facilitate such health
      behaviours even under depletion conditions. METHOD: A laboratory study was
      conducted involving an analytic sample of 85 undergraduates (mean age = 20.08, SD
      = 3.96; female: n= 63). Depletion was manipulated by having participants watch a
      humorous video while suppressing their responses (depletion condition) or
      remaining natural (non-depletion condition). The activation of participants'
      health goals was then manipulated by subtly exposing (goal-priming condition) or
      not exposing (non-priming condition) participants to health-related words in a
      Scrambled Sentence Task. Finally, snacking was measured using a bogus taste-test.
      RESULTS AND DISCUSSION: Controlling for initial hunger, snacking was higher among
      depleted compared to non-depleted participants. Snacking was lower among primed
      compared to non-primed participants. The interaction between depletion and goal
      priming was not significant. These findings suggest that depletion should be
      recognised as a risk factor for lapses in health behaviours, and that health goal
      priming may be a useful technique for facilitating such behaviours even when
      individuals are depleted.

PMID- 25772198
TI  - Specific food preferences of older adults with a poor appetite. A forced-choice
      test conducted in various care settings.
AB  - A poor appetite in older adults is an important determinant of reduced food
      intake and undernutrition. Food preferences may influence food intake. The aim of
      this study was to investigate food preferences of older adults with a poor
      appetite and compare these with preferences of older adults with a good appetite.
      Older adults (n = 349, aged 65-101 years) in nursing/residential care homes,
      hospitals or at home receiving home care participated in a computer-based forced
      choice food preference assessment. Self-reported appetite in the past week was
      classified as 'good' or 'poor' using a validated instrument. Food preferences
      were determined by counting the relative frequency of choices for food images
      according to 11 dichotomous categories: high/low 1) protein; 2) fat; 3)
      carbohydrates; 4) fiber; 5) variation; and 6) animal/vegetarian proteins; 7)
      sweet/savory taste; 8) solid/liquid texture; 9) dairy/non-dairy; with/without 10)
      sauce or 11) color variation. Specific food preferences in participants with a
      poor appetite were identified by one-sample t-tests comparing frequencies to the
      expected value of 48. Preference differences between those with a good and a poor
      appetite were analyzed using GLM adjusting for confounders. The results showed
      that older adults with a poor appetite (n = 113; 32.4%) preferred variation (51.6
      vs. 48, P < 0.001), color variation (55.9 vs. 48, P < 0.01), non-dairy (53.0 vs.
      48, P < 0.001), high-fiber (51.8 vs. 48, P < 0.05), and solid texture (53.5 vs.
      48, P < 0.05). Participants with a poor appetite had a higher frequency score for
      variation than participants with a good appetite (51.6 vs. 48.5, P < 0.001). In
      conclusion, older adults with a poor appetite may have specific food preferences.
      Their preference for variation differs from those with a good appetite. These
      results may be used to develop meals that are preferred by older adults with poor
      appetite in order to increase food intake and prevent undernutrition.

PMID- 25772199
TI  - Religion, Sexuality, and Internalized Homonegativity: Confronting Cognitive
      Dissonance in the Abrahamic Religions.
AB  - This research was aimed at investigating how religious beliefs and internalized
      shame predicted homonegativity. An online survey, which consisted of a self
      report questionnaire assessing religious orientation, internalized shame, and
      internalized homonegativity, was completed by 133 Caucasian and Asian gay men.
      The respondents also were asked to write a short answer in which they had to
      explain how they integrated their religion and sexual practices. The quantitative
      analyses of data demonstrated no significant difference in internalized
      homonegativity among the two cultural groups. Internalized homonegativity was
      predicted by the main Abrahamic faiths (i.e. Christianity, Islam, and Judaism)
      and internalized shame. Qualitative analysis showed that gay men who adhere to a
      monotheistic religious faith follow a different path to reconciling their
      religion and homosexuality compared to gay men who adhere to Philosophical/New
      Age religions or to gay men who have no religious faith. The implications of
      these findings as well as directions for future research studies were discussed. 

PMID- 25772200
TI  - Immune protective effect of human alpha-1-antitrypsin gene during beta cell
      transplantation in diabetic mice.
AB  - Type 1 diabetes (T1D) is a chronic autoimmune disease in which beta cells are
      destroyed. Islet transplantation is the most promising therapeutic treatment for
      T1D patients. However, allograft rejection and autoimmune reaction have been
      recognized as primary causes of graft loss after transplantation. Alpha-1
      antitrypsin (AAT) is an important serine protease inhibitor in serum. AAT is
      characterized by anti-inflammation, anti-apoptosis, and induction-specific
      immunological tolerance. In this study, we successfully established NIT-hAAT cell
      lines, which are murine islet beta cell lines with stable expression of human AAT
      (hAAT) gene. These NIT-hAAT cells were transplanted under the left kidney capsule
      of BALB/c diabetic mice. Interestingly, the sustained expression of hAAT in vivo
      can block the inflammatory cell infiltration and reduce the production of
      proinflammatory cytokines to effectively prevent nonspecific inflammation.
      Results showed that hAAT can inhibit the proliferation of lymphocytes, shift the
      balance between Th17 and Treg, and suppress the maturation of dendritic cells.
      Therefore, hAAT can serve as a beneficial immunomodulator that limits immune
      rejection to prolong islet allograft survival and achieve long-term successful
      transplant outcomes.

PMID- 25772201
TI  - GITRL as a genetic adjuvant enhances enterovirus 71 VP1 DNA vaccine
      immunogenicity.
AB  - VP1 protein is the immunodominant capsid protein of enterovirus 71 (EV71) which
      is responsible for large outbreaks of hand, foot and mouth disease. It has been
      reported that glucocorticoid-induced tumor necrosis factor receptor-related
      protein (GITR) and its ligand (GITRL) are involved in modulating both innate and
      adaptive immune responses. In this study, a DNA vaccine vector encoding EV71 VP1
      gene and mGITRL gene (pIRES/VP1/mGITRL) was constructed. And female Balb/c mice
      were immunized intramuscularly with the DNA vaccine. Compared with the groups
      immunized with pIRES, pIRES/VP1, pIRES/mGITRL and PBS, the inoculation of
      pIRES/VP1/mGITRL induced a higher levels of EV71 VP1-specific antibody and
      specific antibody-forming cells. However, significantly higher levels of
      CD4(+)Th1, Th2 and CD8(+)IFN-gamma(+)T cells were found in the pIRES/VP1/mGITRL
      group compared with control groups. Our results demonstrate that a novel DNA
      vaccine, expressing VP1 and mGITRL, could effectively elicit both humoral and
      cell-mediated immune responses against EV71 VP1 in mice. Thus, the mGITRL may be
      used as molecular adjuvant for EV71 DNA vaccine.

PMID- 25772202
TI  - The changing landscape of lung donation for transplantation.

PMID- 25772203
TI  - Macrophage Phenotype in the Ocular Surface of Experimental Murine Dry Eye
      Disease.
AB  - To evaluate the phenotype of macrophages in the cornea and conjunctiva of C57BL/6
      mice with induced experimental dry eye. C57BL/6 mice exposed to desiccating
      stress (DS) were evaluated at 1, 5, and 10 days and C57BL/6 mice maintained in
      non-stressed environment were used as controls. Whole eyes and adnexa were
      excised for histology or used for gene expression analysis. Location and
      phenotype of macrophages infiltrating the cornea and conjunctiva was evaluated by
      immunofluorescence analysis. Quantitative polymerase chain reaction evaluated
      macrophage markers and T cell-related and inflammatory cytokine expression in
      cornea and conjunctiva. Immunofluorescence staining demonstrated that macrophages
      reside in the conjunctiva of control and dry eye mice and their number did not
      change with DS. Real-time RT-PCR demonstrated that the level of M1 macrophage
      marker, iNOS, increased prominently in the conjunctiva at DS 10 days. In
      contrast, there was a non-significant decrease of the M2 marker Arg1 with DS. The
      levels of inflammatory cytokine, IL-12a mRNA transcript in the conjunctiva
      increased significantly at DS1 and decreased at DS5, while levels of IL-18 were
      significantly increased at DS 10. Macrophages reside in the ocular surface
      tissues of C57BL/6 mice. Although the number of macrophages in the conjunctiva
      does not change, evidence of inflammatory M1 activation after desiccating stress
      was observed. Better understanding of phagocyte diversity and activation in dry
      eye disease provide a basis for the development of phagocyte-targeted therapeutic
      strategies.

PMID- 25772205
TI  - Dengue is still an imported disease in China: a case study in Guangzhou.
AB  - Dengue virus and its four serotypes (DENV 1-4) infect approximately 390 million
      people worldwide each year, with most cases in tropical and subtropical regions.
      Because of repeated introduction of DENV from epidemic regions and suitable
      weather conditions, many regions have shifted from hypo-endemicity to hyper
      endemicity over recent decades. Since the first dengue outbreak in 1978, it is
      crucial to understand the current situation in China over nearly 40 years. The
      purpose of the study was to examine whether dengue in China was endemic or not,
      which is essential for relevant dengue control and prevention strategy
      implementation in China. The study, combining epidemiological characteristics of
      dengue from the disease notification system, phylogenetic and phylogeographic
      analyses, showed that all four serotypes had been detected in Guangzhou, China,
      which was dominated by DENV 1-2. The Maximum Likelihood tree analytic results
      showed that the virus detected in Guangzhou localized in different clades, except
      of virus of 2002 and 2003 clustered together. There existed the mutual
      introductions between Guangzhou and Southeast Asia. Most of the viruses were
      imported from Southeast Asia and the sources of outbreaks in Guangzhou mainly
      originated from Thailand, Indonesia, and the Philippines. The study indicates
      that dengue in China still remains as an imported disease, with the possibility
      of localization.

PMID- 25772204
TI  - Highly divergent 18S rRNA gene paralogs in a Cryptosporidium genotype from
      eastern chipmunks (Tamias striatus).
AB  - Cryptosporidium is an apicomplexan parasite that causes the disease
      cryptosporidiosis in humans, livestock, and other vertebrates. Much of the
      knowledge on Cryptosporidium diversity is derived from 18S rRNA gene (18S rDNA)
      phylogenies. Eukaryote genomes generally have multiple 18S rDNA copies that
      evolve in concert, which is necessary for the accurate inference of phylogenetic
      relationships. However, 18S rDNA copies in some genomes evolve by a birth-and
      death process that can result in sequence divergence among copies. Most notably,
      divergent 18S rDNA paralogs in the apicomplexan Plasmodium share only 89-95%
      sequence similarity, encode structurally distinct rRNA molecules, and are
      expressed at different life cycle stages. In the present study, Cryptosporidium
      18S rDNA was amplified from 28/72 (38.9%) eastern chipmunks (Tamias striatus).
      Phylogenetic analyses showed the co-occurrence of two 18S rDNA types, Type A and
      Type B, in 26 chipmunks, and Type B clustered with a sequence previously
      identified as Cryptosporidium chipmunk genotype II. Types A and B had a sister
      group relationship but shared less than 93% sequence similarity. In contrast,
      actin and heat shock protein 70 gene sequences were homogeneous in samples with
      both Types A and B present. It was therefore concluded that Types A and B are
      divergent 18S rDNA paralogs in Cryptosporidium chipmunk genotype II. Substitution
      patterns in Types A and B were consistent with functionally constrained
      evolution; however, Type B evolved more rapidly than Type A and had a higher G+C
      content (46.3% versus 41.0%). Oocysts of Cryptosporidium chipmunk genotype II
      measured 4.17 MUm (3.73-5.04 MUm) * 3.94 MUm (3.50-4.98 MUm) with a length-to
      width ratio of 1.06 +/- 0.06 MUm, and infection occurred naturally in the
      jejunum, cecum, and colon of eastern chipmunks. The findings of this study have
      implications for the use of 18S rDNA sequences to infer phylogenetic
      relationships.

PMID- 25772206
TI  - Analysis of grayscale characteristics in images of labeled microtubules from
      cultured cardiac myocytes.
AB  - Microtubules of cardiac myocytes depolymerize after a hypoxic insult or treatment
      with colchicine. However, little attention has been paid to quantifying changes
      in microtubule distribution when using fluorescent images. We converted
      fluorescence images of labeled microtubules in H9C2 cardiac myocytes to grayscale
      images, then filtered the images to remove any noise, and used grayscale
      histograms to quantify features of the images. The results show that parameters
      such as the mean, variance, skewness, kurtosis, energy, and entropy can be used
      to quantitatively describe the distribution of microtubules in cells.
      Quantitative characteristics of microtubule distribution were similar after
      culturing cells under hypoxic conditions or after treatment with colchicine.
      These results parallel those described for neonatal rat cardiac myocytes
      following ischemia and hypoxia. In addition, we provide a method for internal
      segmentation of the cells, which revealed that microtubular depolymerization was
      more evident near the cell membrane following hypoxia or colchicine treatment. 

PMID- 25772207
TI  - Can computational goals inform theories of vision?
AB  - One of the most lasting contributions of Marr's posthumous book is his
      articulation of the different "levels of analysis" that are needed to understand
      vision. Although a variety of work has examined how these different levels are
      related, there is comparatively little examination of the assumptions on which
      his proposed levels rest, or the plausibility of the approach Marr articulated
      given those assumptions. Marr placed particular significance on computational
      level theory, which specifies the "goal" of a computation, its appropriateness
      for solving a particular problem, and the logic by which it can be carried out.
      The structure of computational level theory is inherently teleological: What the
      brain does is described in terms of its purpose. I argue that computational level
      theory, and the reverse-engineering approach it inspires, requires understanding
      the historical trajectory that gave rise to functional capacities that can be
      meaningfully attributed with some sense of purpose or goal, that is, a
      reconstruction of the fitness function on which natural selection acted in
      shaping our visual abilities. I argue that this reconstruction is required to
      distinguish abilities shaped by natural selection-"natural tasks" -from
      evolutionary "by-products" (spandrels, co-optations, and exaptations), rather
      than merely demonstrating that computational goals can be embedded in a Bayesian
      model that renders a particular behavior or process rational. 

PMID- 25772208
TI  - Resilience in Families With Adolescents Suffering From Traumatic Brain Injuries.
AB  - PURPOSE: This study aims to coconstruct the building blocks for an intervention
      program to support family resilience in conjunction with families with an
      adolescent suffering from traumatic brain injury and rehabilitation
      professionals. DESIGN: This is a qualitative and inductive study, supported by a
      collaborative research approach. METHODS: Based on the complex intervention
      design and validation model, the investigator follows a three-stage data
      collection process: (1) identifying the building blocks of the intervention
      program in the eyes of families and rehabilitation professionals, (2)
      prioritizing, and (3) validating the building blocks with the same participants.
      FINDINGS: After analyzing the data, the investigator identifies five encompassing
      themes as the building blocks of the intervention program. CONCLUSIONS/CLINICAL
      RELEVANCE: This study offers promising avenues for practitioners and researchers
      in nursing and other fields with respect to the implementation of concrete
      strategies to support the resilience process of families facing particularly
      difficult times in their lives.

PMID- 25772209
TI  - The pathway not taken: understanding 'omics data in the perinatal context.
AB  - OBJECTIVE: 'Omics analysis of large datasets has an increasingly important role
      in perinatal research, but understanding gene expression analyses in the fetal
      context remains a challenge. We compared the interpretation provided by a widely
      used systems biology resource (ingenuity pathway analysis [IPA]) with that from
      gene set enrichment analysis (GSEA) with functional annotation curated
      specifically for the fetus (Developmental FunctionaL Annotation at Tufts
      [DFLAT]). STUDY DESIGN: Using amniotic fluid supernatant transcriptome datasets
      previously produced by our group, we analyzed 3 different developmental
      perturbations: aneuploidy (Trisomy 21 [T21]), hemodynamic (twin-twin transfusion
      syndrome [TTTS]), and metabolic (maternal obesity) vs sex- and gestational age
      matched control subjects. Differentially expressed probe sets were identified
      with the use of paired t-tests with the Benjamini-Hochberg correction for
      multiple testing (P < .05). Functional analyses were performed with IPA and
      GSEA/DFLAT. Outputs were compared for biologic relevance to the fetus. RESULTS:
      Compared with control subjects, there were 414 significantly dysregulated probe
      sets in T21 fetuses, 2226 in TTTS recipient twins, and 470 in fetuses of obese
      women. Each analytic output was unique but complementary. For T21, both IPA and
      GSEA/DFLAT identified dysregulation of brain, cardiovascular, and integumentary
      system development. For TTTS, both analytic tools identified dysregulation of
      cell growth/proliferation, immune and inflammatory signaling, brain, and
      cardiovascular development. For maternal obesity, both tools identified
      dysregulation of immune and inflammatory signaling, brain and musculoskeletal
      development, and cell death. GSEA/DFLAT identified substantially more
      dysregulated biologic functions in fetuses of obese women (1203 vs 151). For all
      3 datasets, GSEA/DFLAT provided more comprehensive information about brain
      development. IPA consistently provided more detailed annotation about cell death.
      IPA produced many dysregulated terms that pertained to cancer (14 in T21, 109 in
      TTTS, 26 in maternal obesity); GSEA/DFLAT did not. CONCLUSION: Interpretation of
      the fetal amniotic fluid supernatant transcriptome depends on the analytic
      program, which suggests that >1 resource should be used. Within IPA, physiologic
      cellular proliferation in the fetus produced many "false positive" annotations
      that pertained to cancer, which reflects its bias toward adult diseases. This
      study supports the use of gene annotation resources with a developmental focus,
      such as DFLAT, for 'omics studies in perinatal medicine.

PMID- 25772210
TI  - The role of preanalytical glycolysis in the diagnosis of gestational diabetes
      mellitus in obese women.
AB  - OBJECTIVE: The objective of this prospective observational study was to determine
      whether the preanalytical management of maternal plasma glucose samples had a
      significant effect on glucose measurements in obese pregnant women. STUDY DESIGN:
      Based on the accurate calculation of body mass index in the first trimester,
      obese women were recruited at their convenience. In 1 cohort, fasting glucose
      level was measured in early pregnancy; in the other cohort, an oral glucose
      tolerance test was performed at 24-28 weeks' gestation. Paired samples were taken
      from all women in both cohorts. The first sample was transferred to the
      laboratory in iced water for immediate analysis (fast-tracked analysis). The
      second sample was not placed on ice and transferred according to established
      hospital practices (hospital-tracked analysis). RESULTS: Of the 24 women who had
      a fasting glucose test in early pregnancy, the result was abnormal (>=5.1 mmol/L)
      in 7 women (29%) with hospital-tracked analysis compared with 16 women (67%) with
      fast-tracked analysis (P < .01). The mean phlebotomy-analysis interval was 119
      minutes for the hospital-tracked samples compared with 23 minutes for the fast
      tracked samples (P < .001). Of the 24 women who had a glucose tolerance test, the
      fasting glucose level was abnormal in 4 women (17%) after hospital-tracked
      analysis compared with 13 women (54%) after fast-tracked analysis (P < .01). The
      hospital-tracked phlebotomy-analysis interval for the fasting sample of the 24-28
      week oral glucose tolerance test cohort was 166 minutes compared with 25 minutes
      for the fast-tracked samples (P < .001). CONCLUSION: Unless maternal fasting
      glucose samples are transported on ice and analyzed immediately in the
      laboratory, gestational diabetes mellitus will be underdiagnosed in obese women.

PMID- 25772211
TI  - Prevalence and patterns of marijuana use among pregnant and nonpregnant women of
      reproductive age.
AB  - OBJECTIVE: The objective of the study was to provide national prevalence,
      patterns, and correlates of marijuana use in the past month and past 2-12 months
      among women of reproductive age by pregnancy status. STUDY DESIGN: Data from 2007
      2012 National Surveys on Drug Use and Health, a cross-sectional nationally
      representative survey, identified pregnant (n = 4971) and nonpregnant (n =
      88,402) women 18-44 years of age. Women self-reported marijuana use in the past
      month and past 2-12 months (use in the past year but not in the past month).
      chi(2) statistics and adjusted prevalence ratios were estimated using a weighting
      variable to account for the complex survey design and probability of sampling.
      RESULTS: Among pregnant women and nonpregnant women, respectively, 3.9% (95%
      confidence interval [CI], 3.2-4.7) and 7.6% (95% CI, 7.3-7.9) used marijuana in
      the past month and 7.0% (95% CI, 6.0-8.2) and 6.4% (95% CI, 6.2-6.6) used in the
      past 2-12 months. Among past-year marijuana users (n = 17,934), use almost daily
      was reported by 16.2% of pregnant and 12.8% of nonpregnant women; and 18.1% of
      pregnant and 11.4% of nonpregnant women met criteria for abuse and/or dependence.
      Approximately 70% of both pregnant and nonpregnant women believe there is slight
      or no risk of harm from using marijuana once or twice a week. Smokers of tobacco,
      alcohol users, and other illicit drug users were 2-3 times more likely to use
      marijuana in the past year than respective nonusers, adjusting for
      sociodemographic characteristics. CONCLUSION: More than 1 in 10 pregnant and
      nonpregnant women reported using marijuana in the past 12 months. A considerable
      percentage of women who used marijuana in the past year were daily users, met
      abuse and/or dependence criteria, and were polysubstance users. Comprehensive
      screening, treatment for use of multiple substances, and additional research and
      patient education on the possible harms of marijuana use are needed for all women
      of reproductive age.

PMID- 25772212
TI  - A randomized controlled trial of birth simulation for medical students.
AB  - OBJECTIVE: The objective of the study was to evaluate the effectiveness of a high
      fidelity birth simulator (Noelle; Gaumard Scientific, Coral Gables, FL) compared
      with a lower-cost, low-tech, birth simulator (MamaNatalie; Laerdal Medical,
      Stavanger, Norway) in teaching medical students how to perform a spontaneous
      vaginal delivery (SVD). STUDY DESIGN: Prior to the obstetrics-gynecology
      clerkship, students were randomly assigned to 2 groups. The MamaNatalie group
      (MG) completed 45 minutes of SVD simulation using an obstetrical abdominal-pelvic
      model worn by an obstetrics-gynecology faculty member. The Noelle group (NG)
      completed 45 minutes of SVD simulation using a high-fidelity, computer-controlled
      mannequin facilitated by an obstetrics-gynecology faculty member. The primary
      outcome was student performance during his or her first SVD as rated by
      supervising preceptors. Surveys were also completed by students on confidence in
      performing steps of a SVD (secondary outcome). RESULTS: One hundred ten medical
      students (95% of those eligible) participated in this research study. The final
      postclerkship survey was completed by 93 students (85% follow-up rate). There
      were no significant differences in performance of SVD steps between MG and NG
      students as rated by preceptors. The SVD step with the least involvement by
      students was controlling the head (20.5% in MG, 23.3% in NG performed step with
      hands-off supervision). Delivery of the placenta was the SVD step with the most
      involvement (65.9% in MG, 52.3% in NG performed step with hands-off supervision).
      Baseline presimulation confidence levels were similar between MG and NG. On the
      immediate postsimulation survey of confidence, MG students were significantly
      more confident in their ability to deliver the abdomen and legs and perform
      fundal massage with hands-off supervision (P < .05) than NG students. Following
      the clerkship, MG students were significantly more confident in their ability to
      control the head and deliver the abdomen and legs (P < .05) than NG students.
      CONCLUSION: MamaNatalie is as effective as Noelle in training medical students
      how to perform a SVD and may be a useful, lower-cost alternative in teaching
      labor and delivery skills to novice learners. Because birth simulation
      interventions involve both a simulation model and facilitator, research is
      required to further determine the effect of human interaction on learning
      outcomes.

PMID- 25772213
TI  - Dravet syndrome in Sweden: a population-based study.
AB  - AIM: To assess the prevalence and incidence of Dravet syndrome in children
      diagnosed in Sweden between 2007 and 2011, and to describe neurological
      comorbidity, disease course, phenotypes, and treatment effects. METHOD: All
      neuropaediatricians at university and county hospitals were asked to supply
      information for patients that matched the electro-clinical profile of Dravet
      syndrome. Genetic laboratories and referral clinicians were also contacted and
      requested to supply information. RESULTS: The estimated incidence was one in 33
      000 live births (95% CI 1:20 400-1:56 200) and prevalence on December 31, 2011
      was one in 45 700 children aged less than 18 years of age (95% CI 1:33 800-1:63
      400). The median age of the 42 children (18 males, 24 females) was 7 years (range
      1-17y), the median age at seizure onset was 6 months (range 0-12mo), and the
      median age at diagnosis was 3 years (range 1-14y). A mutation in the SCN1A gene
      was found in 37 patients (88%), four were familial. Intellectual disability was
      diagnosed in 28 (67%) children, and 18 out of 30 patients investigated had autism
      spectrum disorder. Thirty participants had neurological deficits. Stiripentol, as
      an add-on medication, was used in 18 patients. Among these patients, seven were
      seizure free, six had >50% seizure reduction, and five <50% seizure reduction.
      INTERPRETATION: This is the first population-based study of Dravet syndrome in
      Sweden. Our data confirm international findings of incidence and highlights the
      severe and progressive course of this genetic epilepsy syndrome.

PMID- 25772214
TI  - Flexible, 31-Channel breast coil for enhanced parallel imaging performance at 3T.
AB  - PURPOSE: To design, build, and characterize the performance of a novel 3T, 31
      channel breast coil. METHODS: A flexible breast coil, accommodating all breast
      sizes while preserving close to unity filling factors in all configurations, was
      designed and built. Its performance was compared to the performance of the
      current state-of-the-art, 16 channel breast coil (Sentinelle coil, Hologic,
      Bedford, MA, USA), in phantoms and in vivo. RESULTS: Better axilla coverage and
      lower inter-coil coupling (12% versus 26%, as characterized by the average off
      diagonal elements of the noise correlation matrix) was exhibited by our 31
      channel coil compared with the 16-channel coil. Breast area signal-to-noise ratio
      increases of 68% (phantom) and 28% +/- 31% (in vivo) were observed when the 31
      channel coil was used. For the 31-channel/16-channel arrays, respectively, two
      dimensional acceleration factors of left/right * superior/inferior = 4.3 * 2.4
      resulted in average g-factors of 1.10/1.68 (in vitro) and 1.28/2.75 (in vivo);
      acceleration factors of left/right * anterior/posterior = 3.0 * 2.8 resulted in
      average g-factors of 1.06/1.54 (in vitro) and 1.05/1.12 (in vivo). CONCLUSION: A
      high performance breast coil was built; its capabilities were demonstrated in
      phantom and normal volunteer imaging experiments.

PMID- 25772216
TI  - Big, strong, neutral, twisted, and chiral pi acids.
AB  - General synthetic access to expanded pi-acidic surfaces of variable size,
      topology, chirality, and pi acidity is reported. The availability of pi surfaces
      with these characteristics is essential to develop the functional relevance of
      anion-pi interactions with regard to molecular recognition, translocation, and
      transformation. The problem is that, with expanded pi surfaces, the impact of
      electron-withdrawing substituents decreases and the high pi acidity needed for
      strong anion-pi interactions can be more difficult to obtain. To overcome this
      problem, it is herein proposed to build large surfaces from smaller fragments and
      connect these fragments with bridges that are composed only of single atoms. Two
      central surfaces for powerful anion-pi interactions, namely, perfluoroarenes and
      naphthalenediimides (NDIs), were selected as fragments and coupled with through
      sulfide bridges. Their oxidation to sulfoxides and sulfones, as well as fluorine
      substitution in the peripheral rings, provides access to the full chemical space
      of relevant pi acidities. According to cyclic voltammetry, LUMO levels range from
      -3.96 to -4.72 eV. With sulfoxide bridges, stereogenic centers are introduced to
      further enrich the intrinsic planar chirality of the expanded surfaces. The
      stereoisomers were separated by chiral HPLC and characterized by X-ray
      crystallography. Their topologies range from chairs to pi boats, and the latter
      are reminiscent of the cation-pi boxes in operational neuronal receptors. With
      pentafluorophenyl acceptors, the pi acidity of NDIs with two sulfoxide groups in
      the core reaches -4.45 eV, whereas two sulfone moieties give a value of -4.72 eV,
      which is as low as with four ethyl sulfone groups, that is, a pi superacid near
      the limit of existence. Beyond anion-pi interactions, these conceptually
      innovative pi-acidic surfaces are also of interest as electron transporters in
      conductive materials.

PMID- 25772215
TI  - Evaluation of WO 2012/177618 A1 and US-2014/0179750 A1: novel small molecule
      antagonists of prostaglandin-E2 receptor EP2.
AB  - Recent studies underscore that prostaglandin-E2 exerts mostly proinflammatory
      effects in chronic CNS and peripheral disease models, mainly through a specific
      prostanoid receptor EP2. However, very few highly characterized EP2 receptor
      antagonists have been reported until recently, when Pfizer and Emory University
      published two distinct classes of EP2 antagonists with good potency, selectivity
      and pharmacokinetics. The purpose of this article is to evaluate recently
      published patents WO 2012/177618 A1 and US-2014/0179750 A1 from Emory, which
      describe a number of cinnamic amide- and amide-derivatives as a potent
      antagonists of EP2 receptor, and their neuroprotective effects in in vitro and in
      an in vivo model. A selected compound from this patent(s) also attenuates
      prostate cancer cell growth and invasion in vitro, suggesting these compounds
      should be developed for therapeutic use. 

PMID- 25772217
TI  - The triangular intermuscular space: An uncommon sentinel node location in
      melanoma of the upper arm.

PMID- 25772218
TI  - Malignant adenomyoepithelioma of the breast: a review.
AB  - Malignant adenomyoepithelioma (MAME) of the breast is a rare lesion characterized
      by dual population of epithelial and myoepithelial cells which one or both
      components show malignant features. We report a case of MAME of the breast in a
      46-year-old woman diagnosed by fine-needle aspiration with extensive review of
      the literature. Classification, clinical presentation, cyto-pathologic, and
      immunohistochemical features are described. This lesion showed both malignant
      components of epithelial and myoepithelial cells in cytology and histology. The
      malignancy was convincingly supported by high mitotic figures, pleomorphism, and
      invasion in tissue sections. This review of MAMEs showed that cyto-histologic
      diagnosis is difficult and should be supported by immunohistochemical study. 

PMID- 25772219
TI  - Composition of extracellular polymeric substances in a partial nitrification
      reactor treating high ammonia wastewater and nitrous oxide emission.
AB  - The objective of this study was to characterize the composition of extracellular
      polymeric substances (EPS) during the achievement of partial nitrification and
      subsequent nitrous oxide (N2O) emission treating high ammonia wastewater. After
      operation of 120days, the reactor achieved high ammonia removal efficiency and
      stable nitrite accumulation. The average size of sludge flocs in the reactor
      increased from 102.6 to 258.5MUm. The main compositions of EPS, including protein
      (PN) and polysaccharide (PS), increased to 65.46+/-3.27 and 21.63+/-1.08mg/g VSS,
      respectively. Results of three-dimensional excitation-emission matrix
      spectroscopy implied that EPS transferred to tryptophan PN-like and humic acid
      like substrates. N2O emission accounts for 11.67% of removed nitrogen during the
      steady state of partial nitrification reactor. The obtained results could
      contribute a better understanding the achievement of partial nitrification
      through the composition changes of EPS, and provide more information to determine
      nitrogen removal by considering N2O emission. 

PMID- 25772220
TI  - Biomass-derived nitrogen self-doped porous carbon as effective metal-free
      catalysts for oxygen reduction reaction.
AB  - Biomass-derived nitrogen self-doped porous carbon was synthesized by a facile
      procedure based on simple pyrolysis of water hyacinth (eichhornia crassipes) at
      controlled temperatures (600-800  degrees C) with ZnCl2 as an activation reagent.
      The obtained porous carbon exhibited a BET surface area up to 950.6 m(2) g(-1),
      and various forms of nitrogen (pyridinic, pyrrolic and graphitic) were found to
      be incorporated into the carbon molecular skeleton. Electrochemical measurements
      showed that the nitrogen self-doped carbons possessed a high electrocatalytic
      activity for ORR in alkaline media that was highly comparable to that of
      commercial 20% Pt/C catalysts. Experimentally, the best performance was
      identified with the sample prepared at 700  degrees C, with the onset potential
      at ca. +0.98 V vs. RHE, that possessed the highest concentrations of pyridinic
      and graphitic nitrogens among the series. Moreover, the porous carbon catalysts
      showed excellent long-term stability and much enhanced methanol tolerance, as
      compared to commercial Pt/C. The performance was also markedly better than or at
      least comparable to the leading results in the literature based on biomass
      derived carbon catalysts for ORR. The results suggested a promising route based
      on economical and sustainable biomass towards the development and engineering of
      value-added carbon materials as effective metal-free cathode catalysts for
      alkaline fuel cells. 

PMID- 25772221
TI  - Higher adiponectin and lower hemoglobin levels in older men: causal or confounded
      by androgens?

PMID- 25772222
TI  - [Impact of ageing on driving: decline and compensatory strategies].
AB  - INTRODUCTION: Driving by the elderly is a growing reality, and an activity that
      helps to maintain a sense of personal freedom. But the driving quality can be
      affected by aging. Therefore, the objective of this study is to compare the
      perception of a group of drivers on the age-related changes and the adjustments
      made in the driving depending on age. MATERIAL AND METHODS: A sample of 312
      drivers from 20 to 80 years-old were recruited from medical centers for renewal
      of driving license, as well as in license points recovery centers. The
      participants were given a questionnaire on driving characteristics and
      questionnaire on driving adjustments. RESULTS: There were statistically
      significant differences in both the perceived decline and in compensatory
      adjustments, noting that drivers age 65 years and older scored higher means than
      others. The group from 70 to 80-years-old used compensatory strategies: "Do not
      drive if it rains" "avoid overtaking", "Do not drive at night," "only drive in
      certain areas" or "park in a line". CONCLUSIONS: Since age influences driving,
      the greater use compensatory strategies lessens the impact that aging has on this
      skill.

PMID- 25772223
TI  - Heat stress, divergent nutrition level, and late pregnancy in hair sheep: effects
      upon cotyledon development and litter weight at birth.
AB  - The effect of two divergent nutritional levels during late pregnancy upon some
      physiological variables and the number (NC) and diameter (DC) of placental
      cotyledons along with litter weight at birth (LWB) on heat-stressed (42-45 
      degrees C) hair ewes was evaluated. Multiparous Katahdin x Pelibuey ewes (n = 24)
      at the onset of the 3/3 of pregnancy were randomly assigned to two treatments (n
      = 12): (1) non-nutritionally restricted (NNR) ewes, with free access to wheat
      straw plus 500 g/day of concentrate, and (2) nutritionally restricted (NR) ewes,
      receiving only wheat straw ad libitum. On days 100, 115, 130, and 145 of
      gestation, the body weight (BW), body condition score (BCS), rectal temperature
      (RT), respiration rate (RR) were registered in the afternoon (15:00) while the
      temperature-humidity index (THI) was calculated. At lambing, NC, DC, and LWB were
      also registered. Analyses considered a completely random design (CRD)-ANOVA with
      repeated measures across time, considering to litter size (LS) as covariable to
      reduce any possible influence of LS upon the response variables along
      experimental diets. BW and BCS were higher in NNR ewes at days 115, 130, and 145.
      Despite RT similarities (P < 0.05) between treatments, RR was greater (P < 0.01)
      in the NNR ewes, particularly towards the end of the experimental period. The
      observed THI averages confirmed severe heat stress conditions on ewes all day
      round across the experimental period, yet, NC, DC, and LWB favored (P < 0.05) to
      the NNR ewes. Despite that NNR ewes faced a significant heat stress based on the
      observed THI values, they consumed a diet with an increased energy-protein
      density, suggesting that the increased RR in the NNR group was exerted as a
      compensatory thermoregulation mechanism. Nutritional supplementation in hair ewes
      besides to an increase the energy body reserves (BW and BCS) also improved both
      the number and size of cotyledons, while generated an increased litter weight at
      birth. 

PMID- 25772224
TI  - Dopaminergic regulation of olfactory type G-protein alpha subunit expression in
      the striatum.
AB  - BACKGROUND: In rodents, the olfactory type G-protein alpha subunit (Galphaolf)
      couples the dopamine D1 receptor (D1R) to adenylyl cyclase, triggering
      intracellular signaling and neuronal activation. In the striatum, Galphaolf is
      enriched in the striosomes. Changes in Galphaolf protein levels have been
      observed after dopamine depletion. However, the regulation of Galphaolf
      expression by dopamine and dopamine receptors is not fully understood. METHODS:
      To address this, Striatal Galphaolf expression pattern was studied in wild-type
      and genetically engineered mice lacking D1R, D2R (D2 receptor), and downstream
      regulatory element antagonist modulator (DREAM) protein whose dopamine levels
      were manipulated. Dopamine depletion was accomplished by 6-hydroxydopamine (6
      OHDA) or by Pitx3 ablation, and dopamine replacement by chronic levodopa (l
      dopa). The Galphaolf levels were analyzed by immunohistochemistry, Western blot,
      and real-time quantitative polymerase chain reaction (RT-qPCR). RESULTS: Our
      results demostrate that Dopamine depletion or inactivation of D1R abolished the
      striosomal pattern of Galphaolf expression and increased Galphaolf protein
      levels. Dopamine replacement in wild-type lesioned mice reestablished both the
      expression pattern and protein levels, but paradoxically increased Galphaolf
      messenger RNA (mRNA). In D1R(-/-) mice, dopamine depletion decreased striatal
      Galphaolf expression, whereas l-dopa did not restore either Galphaolf levels or
      its expression pattern. Inactivation of D2R or changes in the cAMP/PKA signaling
      pathway downstream of Galphaolf did not modify its expression. CONCLUSION: Our
      results show a homeostatic, negative regulation of Galphaolf by dopamine and by
      D1R stimulation, which are also required for the striosomal Galphaolf pattern.
      These results shed light on the regulation of Galphaolf by dopamine signaling
      that could be involved in the pathophysiology of the maladaptive response to
      chronic l-dopa treatment in Parkinson's disease.

PMID- 25772225
TI  - Synthesis of bifunctional molecules containing [12]aneN3 and coumarin moieties as
      effective DNA condensation agents and new non-viral gene vectors.
AB  - A series of bifunctional molecules with different combinations of macrocyclic
      polyamine [12]aneN3 and coumarin moieties, 4a/b and 5a/b, were synthesized by a
      two-step copper(I)-mediated alkyne-azide click reactions between 1,3,5
      tris(azidomethyl)benzene and Boc-protected N-propynyl-[12]aneN3/7
      propynyloxycoumarins. Agarose gel electrophoresis experiments indicated that
      bifunctional molecules 4b and 5b effectively induced complete plasmid DNA
      condensation at concentrations up to 40 MUM. It was found that the structural
      variation had a major impact on the condensation behavior of these compounds. The
      electrostatic interaction involving the [12]aneN3 moiety can be compensated by
      the binding contribution of the coumarin units during the DNA condensation
      process. These two types of interaction showed different effects on the
      reversibility of DNA condensation. Results from studies using dynamic laser
      scattering, atomic force microscopy, and EB replacement assay further supported
      the above conclusion. Cytotoxicity assays on bifunctional compounds 4a/b and 5a/b
      indicated their low cytotoxicity. Results from cellular uptake and cell
      transfection experiments proved that bifunctional compounds 4b and 5b
      successfully served as non-viral gene vectors. Furthermore, methyl substituents
      attached to the coumarin unit (4b and 5b) greatly enhanced their DNA condensation
      capability and gene transfection. These bifunctional molecules, with the
      advantages of lower cytotoxicity, good water solubility, and potential structural
      modification, will have great potential for the development of new non-viral gene
      delivery agents.

PMID- 25772226
TI  - The mitogen-activated protein kinase CgHog1 is required for iron homeostasis,
      adherence and virulence in Candida glabrata.
AB  - Candida glabrata has emerged as a major fungal pathogen over the last two
      decades, although our understanding of its survival strategies inside the
      mammalian host remains rudimentary. An important requirement for survival in vivo
      is the ability to acquire critical nutrients such as iron from host niches of
      varied iron content. In the present study, we demonstrate for the first time that
      C. glabrata cells respond to high external iron levels via activation of two
      stress-responsive mitogen-activated protein kinases, CgHog1 and CgSlt2, and lack
      of either kinase results in sensitivity to the high-iron medium. Furthermore, we
      show that CgHOG1 deletion led to perturbed iron homeostasis (elevated
      intracellular iron content and high mitochondrial aconitase activity), reduced
      survival in macrophages and attenuated virulence in the murine model of
      disseminated candidiasis. Consistently, several genes implicated in iron
      acquisition and storage displayed deregulated expression in the Cghog1? mutant.
      Genome-wide transcriptional profiling analysis revealed upregulation of genes
      implicated in DNA repair, RNA processing and autophagy, and downregulation of
      genes related to cellular respiration and organonitrogen compound metabolism
      under iron-limiting conditions. In contrast, genes involved in the respiratory
      electron transport chain were induced under iron-replete conditions. Gene
      expression microarrays also identified a set of iron-responsive regulon in C.
      glabrata. Lastly, we present evidence for the iron-regulated expression of the
      major adhesin-encoding EPA1 gene, decreased histone deacetylase activity in a
      high-iron environment and increased adherence of iron-surplus-medium-grown C.
      glabrata cells to epithelial cells. Together, our findings yield novel insights
      into iron abundance-based regulation of transcriptional and mitogen-activated
      protein kinase signaling pathways in C. glabrata.

PMID- 25772227
TI  - Exploring the kinetics of gelation and final architecture of enzymatically cross
      linked chitosan/gelatin gels.
AB  - Small-angle neutron scattering (SANS) was used to characterize the nanoscale
      structure of enzymatically cross-linked chitosan/gelatin hydrogels obtained from
      two protocols: a pure chemical cross-linking process (C), which uses the natural
      enzyme microbial transglutaminase, and a physical-co-chemical (PC) hybrid
      process, where covalent cross-linking is combined with the temperature-triggered
      gelation of gelatin, occurring through the formation of triple-helices. SANS
      measurements on the final and evolving networks provide a correlation length
      (xi), which reflects the average size of expanding clusters. Their growth in PC
      gels is restricted by the triple-helices (xi ~ 10s of A), while xi in pure
      chemical gels increases with cross-linker concentration (~100s of A). In
      addition, the shear elastic modulus in PC gels is higher than in pure C gels. Our
      results thus demonstrate that gelatin triple helices provide a template to guide
      the cross-linking process; overall, this work provides important structural
      insight to improve the design of biopolymer-based gels. 

PMID- 25772228
TI  - Core temperature affects scalp skin temperature during scalp cooling.
AB  - BACKGROUND: The efficacy of hair loss prevention by scalp cooling to prevent
      chemotherapy induced hair loss has been shown to be related to scalp skin
      temperature. Scalp skin temperature, however, is dependent not only on local
      cooling but also on the thermal status of the body. OBJECTIVES: This study was
      conducted to investigate the effect of body temperature on scalp skin
      temperature. METHODS: We conducted experiments in which 13 healthy subjects
      consumed ice slurry to lower body temperature for 15 minutes after the start of
      scalp cooling and then performed two 12-minute cycle exercise sessions to
      increase body core temperature. Esophageal temperature (Tes ), rectal temperature
      (Tre ), mean skin temperature (eight locations, Tskin ), and mean scalp
      temperature (five locations, Tscalp ) were recorded. RESULTS: During the initial
      10 minutes of scalp cooling, Tscalp decreased by >15  degrees C, whereas Tes
      decreased by 0.2  degrees C. After ice slurry ingestion, Tes , Tre , and Tskin
      were 35.8, 36.5, and 31.3  degrees C, respectively, and increased after exercise
      to 36.3, 37.3, and 33.0  degrees C, respectively. Tscalp was significantly
      correlated to Tes (r = 0.39, P < 0.01): an increase of 1  degrees C in Tes
      corresponded to an increase of 1.6  degrees C in Tscalp . CONCLUSIONS: Slight
      cooling of patients with an elevated body temperature during scalp cooling
      contributes to the decrease in scalp temperature and may improve the prevention
      of hair loss. This may be useful if the desired decrease of scalp temperature
      cannot be obtained by scalp cooling systems.

PMID- 25772229
TI  - Investigating nanoparticle properties in plasmonic nanoarchitectures with DNA by
      surface plasmon resonance imaging.
AB  - Nanoparticles with different sizes, refractive indices and plasmonic profiles are
      synthesized, labelled with DNA and embedded in DNA-based plasmonic
      nanoarchitectures. The contribution of the different properties to reflectivity
      variation % is rationally investigated by DNA hybridization measurements using
      the surface plasmon resonance imaging (SPRi) technology. 

PMID- 25772230
TI  - Racial/ethnic disparities in prevalence and care of patients with type 2 diabetes
      mellitus.
AB  - BACKGROUND: As of 2012, nearly 10% of Americans had diabetes mellitus. People
      with diabetes are at approximately double the risk of premature death compared
      with those in the same age groups without the condition. While the prevalence of
      diabetes has risen across all racial/ethnic groups over the past 30 years, rates
      are higher in minority populations. The objective of this review article is to
      evaluate the prevalence of diabetes and disease-related comorbidities as well as
      the primary endpoints of clinical studies assessing glucose-lowering treatments
      in African Americans, Hispanics, and Asians. METHODS: As part of our examination
      of this topic, we reviewed epidemiologic and outcome publications. Additionally,
      we performed a comprehensive literature search of clinical trials that evaluated
      glucose-lowering drugs in racial minority populations. For race/ethnicity, we
      used the terms African American, African, Hispanic, and Asian. We searched PubMed
      for clinical trial results from 1996 to 2015 using these terms by drug class and
      specific drug. Search results were filtered qualitatively. RESULTS: Overall, the
      majority of publications that fit our search criteria pertained to native Asian
      patient populations (i.e., Asian patients in Asian countries). Sulfonylureas; the
      alpha-glucosidase inhibitor, miglitol; the biguanide, metformin; and the
      thiazolidinedione, rosiglitazone have been evaluated in African American and
      Hispanic populations, as well as in Asians. The literature on other glucose
      lowering drugs in non-white races/ethnicities is more limited. CONCLUSIONS:
      Clinical data are needed for guiding diabetes treatment among racial minority
      populations. A multi-faceted approach, including vigilant screening in at-risk
      populations, aggressive treatment, and culturally sensitive patient education,
      could help reduce the burden of diabetes on minority populations. To ensure
      optimal outcomes, educational programs that integrate culturally relevant
      approaches should highlight the importance of risk-factor control in minority
      patients.

PMID- 25772231
TI  - Caregivers' and physicians' attitudes to rotigotine transdermal patch versus oral
      Parkinson's disease medication: an observational study.
AB  - OBJECTIVE: To provide real-world data on caregiver and physician perceptions of
      the advantages and disadvantages of rotigotine transdermal patch (Neupro * )
      versus oral Parkinson's Disease (PD) medication. METHODS: Cross-sectional, non
      interventional study in routine clinical practice in Germany (NCT01330290).
      Patients had PD with documented need for care, and had received rotigotine
      transdermal patch as add-on to oral PD treatment for >=1 month. Caregivers/nurses
      and physicians assessed rotigotine transdermal patch versus oral PD medications
      using questionnaires. Specific questions regarding the possible benefits of
      transdermal application were asked and comprised questions on: swallowing
      dysfunction, nausea/vomiting, monitoring therapy, once daily application,
      application independently from meals, application to sleeping patients,
      caregiving efforts (caregivers only) and clinical aspects (physicians only). Each
      question was assessed on a 5 point scale ranging from -2 (major disadvantage) to
      2 (major advantage) compared with oral treatment. Primary outcomes were mean
      total scores of all questions for caregivers/nurses and physicians who provided
      responses for >=4 questions. As there are no validated tools to assess
      physician/caregiver preference in the PD setting, there is no reference against
      which the current findings can be compared; this study serves to pilot the
      questionnaires. RESULTS: Questionnaire responses from 128 caregivers/nurses and
      41 physicians were documented for 147 patients. One hundred (68%) patients had a
      caregiving family member; 40 (27%) were cared for by a nurse. Mean PD duration
      was 8.2 (SD 6.3) years; 136 (93%) patients were taking levodopa. Mean total score
      of caregivers'/nurses' questionnaires was 1.32 (SD 0.67) and of physicians'
      questionnaires was 1.46 (0.32) indicating a perceived advantage of rotigotine
      transdermal patch over oral PD therapy. Mean scores for individual questions were
      in the range 1.03-1.54 for caregivers/nurses and 1.15-1.87 for physicians. When
      given a choice about rationale to prescribe, physicians cited pharmaceutical form
      (patch) in 139 (95%) cases and active agent (rotigotine) in 89 (61%) cases.
      CONCLUSION: Caregivers/nurses and physicians perceived advantages with rotigotine
      transdermal patch compared to an oral PD medication as add-on therapy in patients
      with PD; advantages were observed in aspects of medical treatment as well as in
      everyday situations of caregiving of PD patients.

PMID- 25772232
TI  - Brentuximab vedotin in relapsed/refractory Hodgkin lymphoma post-autologous
      transplant: meta-analysis versus historical data.
AB  - OBJECTIVE: This meta-analysis evaluated the antitumor activity of brentuximab
      vedotin versus historical values in patients with relapsed/refractory Hodgkin
      lymphoma post-autologous stem cell transplantation (ASCT). METHODS: A systematic
      literature review identified studies (1993-February 2013) reporting complete
      remission (CR) rates in patients with relapsed/refractory Hodgkin lymphoma post
      ASCT. Publications reporting CR rates, identified through interrogation of
      multiple electronic databases and manual searches (with search terms used to
      capture 'relapsed', 'refractory', 'HL', and 'ASCT'), were included if they
      reported: >=20 relapsed/refractory Hodgkin lymphoma patients, where >=80% were
      aged >=12 years and >=50% had failed prior ASCT. Overall CR rate was determined
      using a random-effect model, and compared with that reported for brentuximab
      vedotin in a pivotal phase 2 trial (SG035-0003). MAIN OUTCOME MEASURES: Across 17
      evaluable studies of historical or experimental agents (n = 812), the estimated
      overall CR rate was 11.1% (95% confidence interval [CI] 7.0, 17.6; range, 0
      38.5%) versus 33.3% (95% CI 25.3, 43.9) for brentuximab vedotin (p < 0.0001). In
      sensitivity analyses, the estimated overall CR rates for historical/experimental
      agents were 13.6% (95% CI 8.7, 21.4) when only HL trials that reported a CR rate
      of >0% were included (13 studies; n = 696; p = 0.0009 vs. brentuximab vedotin),
      and 9.0% (95% CI 4.9, 16.6) when only HL trials were included where CR definition
      was reported and was measured using the same criteria as in the SG035-0003 study
      (12 studies; n = 562; p = 0.0001 vs. brentuximab vedotin). CONCLUSIONS: Indirect
      comparisons against a heterogeneous historical sample population naturally limit
      our ability to draw comparisons, yet the results from this quantitative meta
      analysis suggest that the antitumor activity of brentuximab vedotin may exceed
      that of other therapies used to treat patients with relapsed/refractory Hodgkin
      lymphoma post-ASCT.

PMID- 25772233
TI  - Pregabalin for painful diabetic peripheral neuropathy: strategies for dosing,
      monotherapy vs. combination therapy, treatment-refractory patients, and adverse
      events.
AB  - OBJECTIVE: Primary care physicians face significant challenges when treating
      painful diabetic peripheral neuropathy (pDPN). The physician must determine the
      best dosing strategy, consider the use of combination therapy, and decide how
      best to treat patients who have responded poorly to other treatment options in
      the past. With a focus on these issues, this paper will review the use of
      pregabalin for the treatment of pDPN in order to provide physicians with clinical
      data needed to develop, in combination with real-world prescribing data,
      effective treatment strategies for this common but challenging type of pain.
      RESEARCH DESIGN AND METHODS: A formal PubMed search, along with a search of
      unpublished data from the Pfizer clinical trial database, was used to identify
      papers describing results from clinical trials of pregabalin in patients with
      pDPN. Papers were selected for inclusion in the review if they addressed the use
      of pregabalin in the context of a head-to-head treatment comparison, use in
      refractory patients, or as part of combination therapy. A discussion of
      pregabalin dosing and adverse events is also presented. CONCLUSIONS: There is
      some difference with respect to the maximum approved dose of pregabalin for the
      treatment of pDPN in the United States (300 mg/day) and European Union (600
      mg/day), though clinical data demonstrate that pregabalin doses >300 mg/day may
      be beneficial in some patients. Pregabalin has shown efficacy (and is approved)
      as a monotherapy for pDPN, although several guidelines recommend combination
      therapy for challenging cases. However, evidence to support combination therapy
      is sparse and the decision of monotherapy vs. combination therapy should be at
      the physician's discretion. There are data demonstrating the efficacy of
      pregabalin in some patients with pDPN who have not responded to other
      pharmacological treatments, including those unresponsive to treatment with
      gabapentin. Clinical guidelines acknowledge the paucity of head-to-head data
      among treatment options, but consistently recommend pregabalin as a first-tier
      treatment for pDPN.

PMID- 25772234
TI  - DUSP10 regulates intestinal epithelial cell growth and colorectal tumorigenesis.
AB  - Dual specificity phosphatase 10 (DUSP10), also known as MAP kinase phosphatase 5
      (MKP5), negatively regulates the activation of MAP kinases. Genetic polymorphisms
      and aberrant expression of this gene are associated with colorectal cancer (CRC)
      in humans. However, the role of DUSP10 in intestinal epithelial tumorigenesis is
      not clear. Here, we showed that DUSP10 knockout (KO) mice had increased
      intestinal epithelial cell (IEC) proliferation and migration and developed less
      severe colitis than wild-type (WT) mice in response to dextran sodium sulphate
      (DSS) treatment, which is associated with increased ERK1/2 activation and Kruppel
      like factor 5 (KLF5) expression in IEC. In line with increased IEC proliferation,
      DUSP10 KO mice developed more colon tumours with increased severity compared with
      WT mice in response to administration of DSS and azoxymethane (AOM). Furthermore,
      survival analysis of CRC patients demonstrated that high DUSP10 expression in
      tumours was associated with significant improvement in survival probability.
      Overexpression of DUSP10 in Caco-2 and RCM-1 cells inhibited cell proliferation.
      Our study showed that DUSP10 negatively regulates IEC growth and acts as a
      suppressor for CRC. Therefore, it could be targeted for the development of
      therapies for colitis and CRC. 

PMID- 25772235
TI  - Identification of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase as a novel
      autophagy regulator by high content shRNA screening.
AB  - Deregulation of autophagy has been linked to multiple degenerative diseases and
      cancer, thus the identification of novel autophagy regulators for potential
      therapeutic intervention is important. To meet this need, we developed a high
      content image-based short hairpin RNA screen monitoring levels of the autophagy
      substrate p62/SQSTM1. We identified 186 genes whose loss caused p62 accumulation
      indicative of autophagy blockade, and 67 genes whose loss enhanced p62
      elimination indicative of autophagy stimulation. One putative autophagy
      stimulator, 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 4 (PFKFB4),
      drives flux through pentose phosphate pathway. Knockdown of PFKFB4 in prostate
      cancer cells increased p62 and reactive oxygen species (ROS), but surprisingly
      increased autophagic flux. Addition of the ROS scavenger N-acetyl cysteine
      prevented p62 accumulation in PFKFB4-depleted cells, suggesting that the
      upregulation of p62 and autophagy was a response to oxidative stress caused by
      PFKFB4 elimination. Thus, PFKFB4 suppresses oxidative stress and p62
      accumulation, without which autophagy is stimulated likely as a ROS
      detoxification response. 

PMID- 25772236
TI  - PML isoforms IV and V contribute to adenovirus-mediated oncogenic transformation
      by functionally inhibiting the tumor-suppressor p53.
AB  - Although modulation of the cellular tumor-suppressor p53 is considered to have
      the major role in E1A/E1B-55K-mediated tumorigenesis, other promyelocytic
      leukemia nuclear body (PML-NB)/PML oncogenic domain (POD)-associated factors
      including SUMO, Mre11, Daxx, as well as the integrity of these nuclear bodies
      contribute to the transformation process. However, the biochemical consequences
      and oncogenic alterations of PML-associated E1B-55K by SUMO-dependent PML-IV and
      PML-V interaction have so far remained elusive. We performed mutational analysis
      to define a PML interaction motif within the E1B-55K polypeptide. Our results
      showed that E1B-55K/PML binding is not required for p53, Mre11 and Daxx
      interaction. We also observed that E1B-55K lacking subnuclear PML localization
      because of either PML-IV or PML-V-binding deficiency was no longer capable of
      mediating E1B-55K-dependent SUMOylation of p53, inhibition of p53-mediated
      transactivation or efficiently transforming primary rodent cells. These results
      together with the observation that E1B-55K-dependent SUMOylation of p53 is
      required for efficient cell transformation, provides evidence for the idea that
      the SUMO ligase activity of the E1B-55K viral oncoprotein is intimately linked to
      its growth-promoting oncogenic activities. 

PMID- 25772237
TI  - Cab45S promotes cell proliferation through SERCA2b inhibition and Ca2+ signaling.
AB  - Cytosolic Ca(2+), closely related to endoplasmic reticulum (ER) Ca(2+), plays a
      critical role in regulating cell proliferation and tumorigenesis. However, the
      role of ER lumen proteins in regulating cytosolic Ca(2+) level remains poorly
      understood. Here, we find that the Cab45S, localizes in the ER lumen, inhibits
      sarco/ER Ca(2+)-ATPase 2b (SERCA2b) activity through its first EF-hand domain
      directly binding to the intra-lumenal loop 4 of SERCA2b, and reduces ER Ca(2+).
      STIM1 activation, induced by the Cab45S-dependent drop in ER Ca(2+), together
      with the upregulation of the plasma membrane Ca(2+) channel TRPC1 ultimately
      increases extracellular Ca(2+) influx. Furthermore, increased cytosolic Ca(2+)
      level elicits Ca(2+)-NFAT signaling and promotes cell proliferation.
      Consistently, in cervical carcinoma patients, Cab45S is upregulated. Thus, our
      data reveal that the ability of Cab45S to inhibit SERCA2b activity is crucial for
      its role as a modulator of cell proliferation and tumor growth. 

PMID- 25772238
TI  - CCAAT/Enhancer binding protein beta controls androgen-deprivation-induced
      senescence in prostate cancer cells.
AB  - The processes associated with transition to castration-resistant prostate cancer
      (PC) growth are not well understood. Cellular senescence is a stable cell cycle
      arrest that occurs in response to sublethal stress. It is often overcome in
      malignant transformation to confer a survival advantage. CCAAT/Enhancer Binding
      Protein (C/EBP) beta function is frequently deregulated in human malignancies and
      interestingly, androgen-sensitive PC cells express primarily the liver-enriched
      inhibitory protein isoform. We found that C/EBPbeta expression is negatively
      regulated by androgen receptor (AR) activity and that treatment of androgen
      sensitive cell lines with anti-androgens increases C/EBPbeta mRNA and protein
      levels. Accordingly, we also find that C/EBPbeta levels are significantly
      elevated in primary PC samples from castration-resistant compared with therapy
      naive patients. Chromatin immunoprecipitation demonstrated enhanced binding of
      the AR to the proximal promoter of the CEBPB gene in the presence of
      dihydroxytestosterone. Upon androgen deprivation, induction of C/EBPbeta is
      facilitated by active transcription as evident by increased histone 3 acetylation
      at the C/EBPbeta promoter. Also, the androgen agonist R1881 suppresses the
      activity of a CEBPB promoter reporter. Loss of C/EBPbeta expression prevents
      growth arrest following androgen deprivation or anti-androgen challenge.
      Accordingly, suppression of C/EBPbeta under low androgen conditions results in
      reduced expression of senescence-associated secretory genes, significantly
      decreased number of cells displaying heterochromatin foci and increased numbers
      of Ki67-positive cells. Ectopic expression of C/EBPbeta caused pronounced
      morphological changes, reduced PC cell growth and increased the number of
      senescent LNCaP cells. Lastly, we found that senescence contributes to PC cell
      survival under androgen deprivation, and C/EBPbeta-deficient cells were
      significantly more susceptible to killing by cytotoxic chemotherapy following
      androgen deprivation. Our data demonstrate that upregulation of C/EBPbeta is
      critical for complete maintenance of androgen deprivation-induced senescence and
      that targeting C/EBPbeta expression may synergize with anti-androgen or
      chemotherapy in eradicating PC.

PMID- 25772239
TI  - WIF1 re-expression in glioblastoma inhibits migration through attenuation of non
      canonical WNT signaling by downregulating the lncRNA MALAT1.
AB  - Glioblastoma is the most aggressive primary brain tumor in adults and due to the
      invasive nature cannot be completely removed. The WNT inhibitory factor 1 (WIF1),
      a secreted inhibitor of WNTs, is systematically downregulated in glioblastoma and
      acts as strong tumor suppressor. The aim of this study was the dissection of WIF1
      associated tumor-suppressing effects mediated by canonical and non-canonical WNT
      signaling. We found that WIF1 besides inhibiting the canonical WNT pathway
      selectively downregulates the WNT/calcium pathway associated with significant
      reduction of p38-MAPK (p38-mitogen-activated protein kinase) phosphorylation.
      Knockdown of WNT5A, the only WNT ligand overexpressed in glioblastoma,
      phenocopied this inhibitory effect. WIF1 expression inhibited cell migration in
      vitro and in an orthotopic brain tumor model, in accordance with the known
      regulatory function of the WNT/Ca(2+) pathway on migration and invasion. In
      search of a mediator for this function differential gene expression profiles of
      WIF1-expressing cells were performed. Metastasis-associated lung adenocarcinoma
      transcript 1 (MALAT1), a long non-coding RNA and key positive regulator of
      invasion, emerged as the top downregulated gene. Indeed, knockdown of MALAT1
      reduced migration in glioblastoma cells, without effect on proliferation. Hence,
      loss of WIF1 enhances the migratory potential of glioblastoma through WNT5A that
      activates the WNT/Ca(2+) pathway and MALAT1. These data suggest the involvement
      of canonical and non-canonical WNT pathways in glioblastoma promoting key
      features associated with this deadly disease, proliferation on one hand and
      invasion on the other. Successful targeting will require a dual strategy
      affecting both canonical and non-canonical WNT pathways. 

PMID- 25772240
TI  - The role of Tcfap2c in tumorigenesis and cancer growth in an activated Neu model
      of mammary carcinogenesis.
AB  - TFAP2C/AP-2gamma influences development of the mammary gland and regulates
      patterns of gene expression in luminal and HER2-amplified breast cancer. The
      roles of TFAP2C in mammary gland tumorigenesis and in pathways critical to cancer
      progression remain poorly understood. To gain greater insight into oncogenic
      mechanisms regulated by TFAP2C, we examined mammary tumorigenesis in MMTV-Neu
      transgenic female mice with or without conditional knockout (KO) of Tcfap2c, the
      mouse homolog of TFAP2C. Loss of Tcfap2c increased the latency of tumorigenesis
      and tumors that formed demonstrated reduced proliferative index and increased
      apoptosis. In addition, tumors formed in Tcfap2c KO animals had a significant
      reduction in Egfr levels without a change in the expression of the Neu oncogene.
      The MMneu-flAP2C cell line was established from tumor tissue derived from MMTV
      Neu/Tcfap2c(L/L) control animals and parallel cell lines with and without
      expression of Tcfap2c were created by transduction with adenovirus-empty and
      adenovirus-Cre, respectively. KO of Tcfap2c in vitro reduced activated
      phosphorylated-Erk, decreased cell viability, repressed tumor growth and was
      associated with attenuation of Egfr expression. Chromatin immunoprecipitation and
      direct sequencing and expression analysis confirmed that Egfr was a Tcfap2c
      target gene in murine, as well as human, mammary carcinoma cells. Furthermore,
      decreased viability of mammary cancer cells was directly related to Egfr
      functional blockade. We conclude that TFAP2C regulates tumorigenesis, cell growth
      and survival in HER2-amplified breast cancer through transcriptional regulation
      of EGFR. The findings have important implications for targeting the EGFR pathway
      in breast cancer. 

PMID- 25772241
TI  - The chemokine receptor CCR7 promotes mammary tumorigenesis through amplification
      of stem-like cells.
AB  - The chemokine receptor CCR7 is widely implicated in breast cancer pathobiology.
      Although recent reports correlated high CCR7 levels with more advanced tumor
      grade and poor prognosis, limited in vivo data are available regarding its
      specific function in mammary gland neoplasia and the underlying mechanisms
      involved. To address these questions we generated a bigenic mouse model of breast
      cancer combined with CCR7 deletion, which revealed that CCR7 ablation results in
      a considerable delay in tumor onset as well as significantly reduced tumor
      burden. Importantly, CCR7 was found to exert its function by regulating mammary
      cancer stem-like cells in both murine and human tumors. In vivo experiments
      showed that loss of CCR7 activity either through deletion or pharmacological
      antagonism significantly decreased functional pools of stem-like cells in mouse
      primary mammary tumors, providing a mechanistic explanation for the tumor
      promoting role of this chemokine receptor. These data characterize the oncogenic
      properties of CCR7 in mammary epithelial neoplasia and point to a new route for
      therapeutic intervention to target evasive cancer stem cells. 

PMID- 25772242
TI  - MOZ (MYST3, KAT6A) inhibits senescence via the INK4A-ARF pathway.
AB  - Cellular senescence is an important mechanism that restricts tumour growth. The
      Ink4a-Arf locus (also known as Cdkn2a), which encodes p16(INK4A) and p19(ARF),
      has a central role in inducing and maintaining senescence. Given the importance
      of cellular senescence in restraining tumour growth, great emphasis is being
      placed on the identification of novel factors that can modulate senescence. The
      MYST-family histone acetyltransferase MOZ (MYST3, KAT6A), first identified in
      recurrent translocations in acute myeloid leukaemia, has been implicated in both
      the promotion and inhibition of senescence. In this study, we investigate the
      role of MOZ in cellular senescence and show that MOZ is a potent inhibitor of
      senescence via the INK4A-ARF pathway. Primary mouse embryonic fibroblasts (MEFs)
      isolated from Moz-deficient embryos exhibit premature senescence, which was
      rescued on the Ink4a-Arf(-/-) background. Importantly, senescence resulting from
      the absence of MOZ was not accompanied by DNA damage, suggesting that MOZ acts
      independently of the DNA damage response. Consistent with the importance of
      senescence in cancer, expression profiling revealed that genes overexpressed in
      aggressive and highly proliferative cancers are expressed at low levels in Moz
      deficient MEFs. We show that MOZ is required to maintain normal levels of histone
      3 lysine 9 (H3K9) and H3K27 acetylation at the transcriptional start sites of at
      least four genes, Cdc6, Ezh2, E2f2 and Melk, and normal mRNA levels of these
      genes. CDC6, EZH2 and E2F2 are known inhibitors of the INK4A-ARF pathway. Using
      chromatin immunoprecipitation, we show that MOZ occupies the Cdc6, Ezh2 and Melk
      loci, thereby providing a direct link between MOZ, H3K9 and H3K27 acetylation,
      and normal transcriptional levels at these loci. This work establishes that MOZ
      is an upstream inhibitor of the INK4A-ARF pathway, and suggests that inhibiting
      MOZ may be one way to induce senescence in proliferative tumour cells. 

PMID- 25772243
TI  - GPNMB cooperates with neuropilin-1 to promote mammary tumor growth and engages
      integrin alpha5beta1 for efficient breast cancer metastasis.
AB  - Glycoprotein nmb (GPNMB) promotes breast tumor growth and metastasis and its
      expression in tumor epithelium correlates with poor prognosis in breast cancer
      patients. Despite its biological and clinical significance, little is known
      regarding the molecular mechanisms engaged by GPNMB. Herein, we show that GPNMB
      engages distinct functional domains and mechanisms to promote primary tumor
      growth and metastasis. We demonstrate that neuropilin-1 (NRP-1) expression is
      increased in breast cancer cells that overexpress GPNMB. Interestingly, the GPNMB
      driven increase in NRP-1 expression potentiated vascular endothelial growth
      factor signaling in breast cancer cells and was required for the growth, but not
      metastasis, of these cells in vivo. Interrogation of RNAseq data sets revealed a
      positive correlation between GPNMB and NRP-1 levels in human breast tumors.
      Furthermore, we ascribe pro-growth and pro-metastatic functions of GPNMB to its
      ability to bind alpha5beta1 integrin and increase downstream signaling in breast
      cancer cells. We show that GPNMB enhances breast cancer cell adhesion to
      fibronectin, increases alpha5beta1 expression and associates with this receptor
      through its RGD motif. GPNMB recruitment into integrin complexes activates Src
      and Fak signaling pathways in an RGD-dependent manner. Importantly, both the RGD
      motif and cytoplasmic tail of GPNMB are required to promote primary mammary tumor
      growth; however, only mutation of the RGD motif impaired the formation of lung
      metastases. Together, these findings identify novel and distinct molecular
      mediators of GPNMB-induced breast cancer growth and metastasis. 

PMID- 25772244
TI  - Aberrant hedgehog signaling is responsible for the highly invasive behavior of a
      subpopulation of hepatoma cells.
AB  - Hepatoma exhibits a series of heterogeneous subpopulations in its cell surface
      markers, tumorigenicity, invasion and metastatic capability. We previously
      demonstrated that the CD133(-)/EpCAM(-) hepatoma subpopulation was more
      metastatic than its counterpart; however, the controlling mechanisms are
      unexplored. The present study aimed to delineate the significance of aberrant
      hedgehog (Hh) signaling in the mediation of metastases. Fluorescence-activated
      cell sorting-enriched CD133(-)/EpCAM(-) (double negative, DN), Huh-7 cells
      underwent a transwell selection for metastatic cells (transwell-selected, TS).
      The TS cells displayed much greater metastatic activity as evidenced by an
      increased invasion rate, extremely upregulated expression of matrix
      metalloproteinase (MMP)-1/2/9 genes compared with DN and double-positive (DP)
      subpopulations. In contrast to DP cells, TS cells lost E-cadherin and were all
      vimentin-positive as shown by immunocytochemistry. There was a transitional
      increase in Gli-1/2 gene expression levels from DP, DN to TS subpopulations,
      which was consistent with elevated Gli-1/2 or Twist-1 protein levels in the
      nuclear fraction. Furthermore, truncated Gli-1 (tGli-1), which transactivates
      molecules involved in metastasis, was detected in the highly invasive Huh-7 cell
      subpopulation, but not in less metastatic hepatoma cells or normal hepatocytes.
      The enhanced metastatic features with increased expression of MMPs as well as the
      presence of twist and snail genes in TS Huh-7 cells were reversed by LDE225, a
      potent Smoothened antagonist. In conclusion, the highly metastatic capability of
      a unique TS subpopulation was highly attributed to significant epithelial
      mesenchymal transition, enhanced Hh activity and aberrant occurrence of a tGli-1
      variant, which appears to be responsible for the highly invasive behavior. 

PMID- 25772245
TI  - The protein tyrosine phosphatase DEP-1/PTPRJ promotes breast cancer cell invasion
      and metastasis.
AB  - DEP-1/PTPRJ is a receptor-like protein tyrosine phosphatase mainly known for its
      antiproliferative and tumor-suppressive functions. Many identified substrates are
      growth factor receptors, and DEP-1 is deleted and/or mutated in human cancers
      including that of the breast. However, DEP-1 was also identified as a promoter of
      Src activation and proinvasive functions in the endothelium, suggesting it could
      perhaps mediate breast cancer invasiveness that is likewise driven by Src family
      kinases. We show here that DEP-1 expression was greater in highly invasive breast
      cancer cells (MDA-MB-231, Hs578T, BT-549) than in the less invasive or
      untransformed cell lines tested (MCF-7, T47D, SK-BR3 and MCF10A). DEP-1 silencing
      experiments in invasive cells demonstrated that moderately expressed and
      catalytically active DEP-1 was required, in collaboration with basal epidermal
      growth factor receptor activity, for Src activation and the phosphorylation of
      its substrate Cortactin, and for their colocalization at the cell's leading edge.
      This correlated with an increased number of cell protrusions, and an enhanced
      capacity of the cells to migrate and invade. Similarly, moderate overexpression
      of DEP-1 in the low-invasive cells resulted in the promotion of their
      invasiveness in an Src-dependent manner. Consistent with these data, the
      expression of endogenous DEP-1 was elevated in a bone metastatic cell line
      derived from MDA-MB-231 cells, and promoted increased Src Y418 and Cortactin Y421
      phosphorylation, as well as pro-MMP9 secretion and Matrigel invasion.
      Importantly, the silencing of DEP-1 in MDA-MB-231 cells greatly decreased their
      ability to metastasize, despite having no effect on tumor growth or angiogenesis.
      Hence, we found that moderate expression of DEP-1 was associated with the
      increased relapse and decreased survival of breast cancer patients. These results
      therefore identify a new and unsuspected role for DEP-1 as a mediator of an
      invasive cell program implicating Src activation and the promotion of breast
      cancer progression. 

PMID- 25772246
TI  - Cell growth density modulates cancer cell vascular invasion via Hippo pathway
      activity and CXCR2 signaling.
AB  - Metastasis of cancer cells involves multiple steps, including their dissociation
      from the primary tumor and invasion through the endothelial cell barrier to enter
      the circulation and finding their way to distant organ sites where they
      extravasate and establish metastatic lesions. Deficient contact inhibition is a
      hallmark of invasive cancer cells, yet surprisingly the vascular invasiveness of
      commonly studied cancer cell lines is regulated by the density at which cells are
      propagated in culture. Cells grown at high density were less effective at
      invading an endothelial monolayer than cells grown at low density. This
      phenotypic difference was also observed in a zebrafish model of vascular invasion
      of cancer cells after injection into the yolk sac and extravasation of cancer
      cells into tissues from the vasculature. The vascular invasive phenotypes were
      reversible. A kinome-wide RNA interference screen was used to identify drivers of
      vascular invasion by panning small hairpin RNA (shRNA) library-transduced
      noninvasive cancer cell populations on endothelial monolayers. The selection of
      invasive subpopulations showed enrichment of shRNAs targeting the large tumor
      suppressor 1 (LATS1) kinase that inhibits the activity of the transcriptional
      coactivator yes-associated protein (YAP) in the Hippo pathway. Depletion of LATS1
      from noninvasive cancer cells restored the invasive phenotype. Complementary to
      this, inhibition or depletion of YAP inhibited invasion in vitro and in vivo. The
      vascular invasive phenotype was associated with a YAP-dependent upregulation of
      the cytokines IL6, IL8 and C-X-C motif ligand 1, 2 and 3. Antibody blockade of
      cytokine receptors inhibited invasion and confirmed that they are rate-limiting
      drivers that promote cancer cell vascular invasiveness and could provide
      therapeutic targets. 

PMID- 25772247
TI  - Inhibition of TGFBIp expression reduces lymphangiogenesis and tumor metastasis.
AB  - Transforming growth factor-beta-induced protein (TGFBIp) is an extracellular
      matrix protein that has a role in a wide range of pathological conditions.
      However, the role of TGFBIp signaling in lymphangiogenesis is poorly understood.
      The purpose of this study was therefore to analyze the effects of TGFBIp on
      lymphangiogenesis and determine whether TGFBIp-related lymphangiogenesis is
      important for the metastasis of tumor cells. TGFBIp increased adhesion,
      migration, and morphologic differentiation of human lymphatic endothelial cells
      (LECs), consistent with an increase in lymphatic vessel sprouting in a three
      dimensional lymphatic ring assay. TGFBIp also induced phosphorylation of
      intracellular signaling molecules SRC, FAK, AKT, JNK and ERK. TGFBIp-induced
      lymphatic vessel sprouting was inhibited by addition of anti-integrin beta3
      antibody and pharmacologic inhibitors of FAK, AKT, JNK or ERK. TGFBIp increased
      both CCL21 expression in LECs, a chemokine that actively recruits tumor cells
      expressing the cognate chemokine receptors to lymphatic vessels and LEC
      permeability by inducing the dissociation of VE-cadherin junctions between LECs
      via the activation of SRC signaling. In vivo, inhibition of TGFBIp expression in
      SW620 cancer cells dramatically reduced tumor lymphangiogenesis and metastasis.
      Collectively, our findings demonstrate that TGFBIp is a lymphangiogenic factor
      contributing to tumor dissemination and represents a potential target to inhibit
      metastasis. 

PMID- 25772249
TI  - Highly accurate scattering spectra of strongly absorbing samples obtained using
      an integrating sphere system by considering the angular distribution of diffusely
      reflected light.
AB  - An integrating sphere system has been used to investigate the estimation error in
      the scattering coefficient for biological tissues. Since the angular distribution
      of diffusely reflected light from a sample may depend on the sample absorbance,
      leakage at the entrance port may affect estimates of the scattering coefficient
      based on measurement of diffuse reflectance. In the present study, the dependence
      of the angular distribution of the diffusely reflected light on the hemoglobin
      (Hb) concentration in a sample was investigated. Subsequently, the effect of the
      entrance port diameter on the error in the scattering coefficient estimated based
      on diffuse reflectance measurements was evaluated. For a biological tissue
      phantom, the angular reflectance distribution at a wavelength of 405 nm, at which
      strong absorption occurred, showed an increasing bias toward specular reflection
      as the Hb concentration was increased. No such concentration dependence was found
      at a wavelength of 664 nm, where the absorbance was low. In addition, it was
      found that the estimation error in the scattering coefficient was reduced for
      smaller entrance port diameters. Therefore, when attempting to determine the
      scattering coefficient for strongly absorbing samples, it is necessary to
      consider both the angular distribution of the diffusely reflected light and the
      optimal entrance port diameter.

PMID- 25772250
TI  - Novice surgeons: do they benefit from 3D laparoscopy?
AB  - In this study, the impact of two-dimensional (2D) and three-dimensional (3D)
      vision on laparoscopic performance of novice surgeons is examined. Twenty-five
      novice surgeons were directed to complete four basic tasks from European Training
      in Basic Laparoscopic Urological Skills (E-BLUS) with both 2D and 3D systems in a
      random order: task 1: needle guidance, task 2: cutting a circle, task 3:
      laparoscopic suturing, and task 4: pegs transfer. Quality and quantity scores for
      each task were measured. Participants completed all of the tasks in one modality
      of vision and than switched to the other. NASA Task Load Index was used for
      subjective workload assessment. Statistically significant differences in favor of
      3D vision were detected in tasks 1 and 4 both in terms of quality and quantity.
      In task 2 and task 3, a significantly better performance was observed with the 3D
      vision only in quantity assessment. The participants who started the tasks in the
      3D vision were better in performing the skills in 2D when compared to the
      participants who started with 2D vision. Overall, the participants reported a
      better perception of depth and spatial orientation with the 3D mode. Subjective
      work load was also lower for the tasks performed in 3D. Novice surgeons tended to
      perform better and felt much more comfortable with 3D in comparison to 2D
      laparoscopy. Even though previous task experience seemed to have an important
      impact on laparoscopic performance regardless of imaging modality, 3D laparoscopy
      seemed to facilitate the learning for novice surgeons. 

PMID- 25772251
TI  - Matrix metalloproteinase 13: a potential intermediate between low expression of
      microRNA-125b and increasing metastatic potential of non-small cell lung cancer.
AB  - Recent findings have suggested that microRNAs may be involved in the regulation
      of metastasis in malignant cancers such as non-small cell lung cancer (NSCLC).
      This study aimed to determine the relationship between expression of miR-125b and
      matrix metalloproteinase 13 (encoded by MMP-13) and the metastatic potential of
      cancer cells in NSCLC. Expression levels of miR-125b transcripts and MMP-13
      proteins were analyzed by quantitative real-time PCR and immunohistochemistry,
      respectively, in tumor tissues and adjacent nontumor tissues from 42 patients
      with NSCLC. The interaction between miR-125b and MMP-13 expression and the
      associations between miR-125b and clinicopathologic data were analyzed. MiR-125 b
      expression levels were decreased in NSCLC tumor tissue samples, which correlated
      with an increased incidence of lymph node metastases, increased pathologic stage,
      increased MMP-13 expression levels, and decreased early progression-free
      survival. Additionally, we have demonstrated that increased levels of miR-125b
      can directly downregulate MMP-13 protein expression and inhibit the invasive
      capabilities of cancer cells. Expression levels of miR-125b were negatively
      correlated with metastatic potential of NSCLC tumors, which may function through
      regulation of MMP-13. 

PMID- 25772248
TI  - Silk-based biomaterials in biomedical textiles and fiber-based implants.
AB  - Biomedical textiles and fiber-based implants (BTFIs) have been in routine
      clinical use to facilitate healing for nearly five decades. Amongst the variety
      of biomaterials used, silk-based biomaterials (SBBs) have been widely used
      clinically viz. sutures for centuries and are being increasingly recognized as a
      prospective material for biomedical textiles. The ease of processing,
      controllable degradability, remarkable mechanical properties and biocompatibility
      have prompted the use of SBBs for various BTFIs for extracorporeal implants, soft
      tissue repair, healthcare/hygiene products and related needs. The present Review
      focuses on BTFIs from the perspective of types and physical and biological
      properties, and this discussion is followed with an examination of the advantages
      and limitations of BTFIs from SBBs. The Review covers progress in surface
      coatings, physical and chemical modifications of SBBs for BTFIs and identifies
      future needs and opportunities for the further development for BTFIs using SBBs. 

PMID- 25772252
TI  - Relationship of fibroblast growth factor 23 and fetuin--A to coronary
      atherosclerosis.
AB  - BACKGROUND: Serum fibroblast growth factor 23 (FGF-23) and fetuin-A are
      established predictors of morbidity and mortality due to cardiovascular disease.
      The objective of the present study is to evaluate the relationship between
      coronary artery disease (CAD) and serum concentrations of FGF-23 and fetuin-A.
      METHODS: A total of 383 subjects who underwent coronary computed tomography
      angiography (CCTA) were included in the study. CCTA detected CAD in 208 patients;
      the rest of the patients had no detectable CAD. RESULTS: Serum FGF-23 and fetuin
      A levels were significantly increased in CAD patients compared to non-CAD
      patients (26.6+/-21.1pg/mL vs. 17.9+/-16.1pg/mL, p=0.001 and 826+/-350mg/L vs.
      595+/-300mg/L, p<0.001, respectively). Serum FGF-23, fetuin-A, low-density
      lipoprotein (LDL)-cholesterol, and uric acid values were elevated in non-diabetic
      patients with CAD when compared to those without CAD. FGF-23, and fetuin-A were
      not significantly different in diabetic patients with CAD when compared to those
      without CAD. Using multivariate logistic regression analysis, we found that age,
      hypertension, LDL-Cholesterol, high-density lipoprotein (HDL)-Cholesterol, hs
      CRP, uric acid, FGF-23 and fetuin-A levels were independently associated with the
      presence of CAD. CONCLUSION: FGF-23 and fetuin-A were positively correlated with
      coronary atherosclerosis Similar trends were seen among diabetic patients, but
      this did not reach statistical significance. FGF-23 and fetuin-A could be used as
      novel risk markers of cardiovascular disease.

PMID- 25772253
TI  - Reversible splenium diffusion weighted MRI changes associated with hypoglycemia.
AB  - Hypoglycemia can manifest as a stroke. MRI diffusion-weighted imaging is the most
      useful technique in diagnosing early ischemic injury. We report two cases of
      transient MRI lesions of the splenium of the corpus callosum related to
      hypoglycemia. Clinicians must be aware of such cases to avoid misdiagnosis. 

PMID- 25772254
TI  - Development and validation of risk assessment models for diabetes-related
      complications based on the DCCT/EDIC data.
AB  - AIM: To derive and validate a set of computational models able to assess the risk
      of developing complications and experiencing adverse events for patients with
      diabetes. The models are developed on data from the Diabetes Control and
      Complications Trial (DCCT) and the Epidemiology of Diabetes Interventions and
      Complications (EDIC) studies, and are validated on an external, retrospectively
      collected cohort. METHODS: We selected fifty-one clinical parameters measured at
      baseline during the DCCT as potential risk factors for the following adverse
      outcomes: Cardiovascular Diseases (CVD), Hypoglycemia, Ketoacidosis,
      Microalbuminuria, Proteinuria, Neuropathy and Retinopathy. For each outcome we
      applied a data-mining analysis protocol in order to identify the best-performing
      signature, i.e., the smallest set of clinical parameters that, considered
      jointly, are maximally predictive for the selected outcome. The predictive models
      built on the selected signatures underwent both an interval validation on the
      DCCT/EDIC data and an external validation on a retrospective cohort of 393
      diabetes patients (49 Type I and 344 Type II) from the Chorleywood Medical
      Center, UK. RESULTS: The selected predictive signatures contain five to fifteen
      risk factors, depending on the specific outcome. Internal validation
      performances, as measured by the Concordance Index (CI), range from 0.62 to 0.83,
      indicating good predictive power. The models achieved comparable performances for
      the Type I and, quite surprisingly, Type II external cohort. CONCLUSIONS: Data
      mining analyses of the DCCT/EDIC data allow the identification of accurate
      predictive models for diabetes-related complications. We also present initial
      evidences that these models can be applied on a more recent, European population.

PMID- 25772255
TI  - Salidroside attenuates chronic hypoxia-induced pulmonary hypertension via
      adenosine A2a receptor related mitochondria-dependent apoptosis pathway.
AB  - Pulmonary arterial hypertension (PAH) is characterized by pulmonary arterial
      remodeling mainly due to excess cellular proliferation and apoptosis resistance
      of pulmonary arterial smooth muscle cells (PASMCs). Salidroside, an active
      ingredient isolated from Rhodiola rosea is proposed to exert protective effects
      against PAH. However, the function of salidroside in PAH has not been
      investigated systematically and the underlying mechanisms are not clear. To
      investigate the effects of salidroside on PAH, the mice in chronic hypoxia model
      of PAH were given by an increasing concentration of salidroside (0, 16 mg/kg, 32
      mg/kg, and 64 mg/kg). After salidroside treatment, the chronic hypoxia-induced
      right ventricular hypertrophy and pulmonary arterial remodeling were attenuated,
      suggesting a protective role played by salidroside in PAH. To explore the
      potential mechanisms, the apoptosis of PASMCs after salidroside treatment under
      hypoxia conditions were determined in vivo and in vitro, and also the
      mitochondria-dependent apoptosis factors, Bax, Bcl-2, cytochrome C, and caspase 9
      were examined. The results revealed that salidroside reversed hypoxia-induced
      cell apoptosis resistance at least partially via a mitochondria-dependent
      pathway. In addition, salidroside upregulated the expression of adenosine A2a
      receptor (A2aR) in lung tissues of mice and in PASMCs in vitro after hypoxia
      exposure. Combined the evidence above, we conclude that salidroside can attenuate
      chronic hypoxia-induced PAH by promoting PASMCs apoptosis via an A2aR related
      mitochondria dependent pathway.

PMID- 25772256
TI  - Nomenclature and traceability debate for biosimilars: small-molecule surrogates
      lend support for distinguishable nonproprietary names.
AB  - INTRODUCTION: The purpose of the present study was to investigate the
      traceability of adverse events (AEs) for branded and generic drugs with identical
      nonproprietary names and to consider potential implications for the traceability
      of AEs for branded and biosimilar biologics. METHODS: Adverse event reports in
      the Food and Drug Administration AE Reporting System (FAERS) were compared with
      those in a commercial insurance claims database (Truven Health MarketScan((r)))
      for 2 drugs (levetiracetam and enoxaparin sodium) with manufacturing or
      prescribing considerations potentially analogous to those of some biosimilars.
      Monthly rates of branded- and generic-attributed AEs were estimated pre- and post
      generic entry. Post-entry branded-to-generic AE relative rate ratios were
      calculated. RESULTS: In FAERS, monthly AE rate ratios during the post-generic
      period showed a pattern in which AE rates for the branded products were greater
      than for the generic products. Differences in rates of brand- and generic
      attributed AEs were statistically significant for both study drugs; the AE rate
      for the branded products peaked at approximately 10 times that of the generic
      levetiracetam products and approximately 4 times that of the generic enoxaparin
      sodium products. In contrast, monthly ratios for the MarketScan data were
      relatively constant over time. CONCLUSION: Use of the same nonproprietary name
      for generic and branded products may contribute to poor traceability of AEs
      reported in the FAERS database due to the significant misattribution of AEs to
      branded products (when those AEs were in fact associated with patient use of
      generic products). To ensure accurate and robust safety surveillance and
      traceability for biosimilar products in the United States, improved product
      identification mechanisms, such as related but distinguishable nonproprietary
      names for biosimilars and reference biologics, should be considered.

PMID- 25772257
TI  - Mechanical fatigue performance of PCL-chondroprogenitor constructs after cell
      culture under bioreactor mechanical stimulus.
AB  - In tissue engineering of cartilage, polymeric scaffolds are implanted in the
      damaged tissue and subjected to repeated compression loading cycles. The
      possibility of failure due to mechanical fatigue has not been properly addressed
      in these scaffolds. Nevertheless, the macroporous scaffold is susceptible to
      failure after repeated loading-unloading cycles. This is related to inherent
      discontinuities in the material due to the micropore structure of the macro-pore
      walls that act as stress concentration points. In this work, chondrogenic
      precursor cells have been seeded in poly-epsilon-caprolactone (PCL) scaffolds
      with fibrin and some were submitted to free swelling culture and others to cyclic
      loading in a bioreactor. After cell culture, all the samples were analyzed for
      fatigue behavior under repeated loading-unloading cycles. Moreover, some
      components of the extracellular matrix (ECM) were identified. No differences were
      observed between samples undergoing free swelling or bioreactor loading
      conditions, neither respect to matrix components nor to mechanical performance to
      fatigue. The ECM did not achieve the desired preponderance of collagen type II
      over collagen type I which is considered the main characteristic of hyaline
      cartilage ECM. However, prediction in PCL with ECM constructs was possible up to
      600 cycles, an enhanced performance when compared to previous works. PCL after
      cell culture presents an improved fatigue resistance, despite the fact that the
      measured elastic modulus at the first cycle was similar to PCL with poly(vinyl
      alcohol) samples. This finding suggests that fatigue analysis in tissue
      engineering constructs can provide additional information missed with traditional
      mechanical measurements.

PMID- 25772258
TI  - Cyclosporin A upregulates ETB receptor in vascular smooth muscle via activation
      of mitogen-activating protein kinases and NF-kappaB pathways.
AB  - Hypertension is one of the most frequent complications of solid organ
      transplantation, and cyclosporin A (CsA) plays a predominant role in the
      pathophysiology of post-transplant hypertension. However, the exact molecular
      mechanisms of CsA-induced hypertension remain obscure. We previously showed that
      CsA increased the mRNA expression and contractile function of endothelin B (ETB)
      receptor in vascular smooth muscle cells. The present study was designed to
      investigate the underlying mechanisms of CsA-induced upregulation of ETB receptor
      in vasculature. Rat mesenteric arteries were incubated with CsA in an organ
      culture system, and results showed that CsA enhanced ETB receptor mRNA in the
      time- and dose-dependent manner, and increased protein expression levels of ETB
      receptor after treatment with CsA 10(-5)M for 6h. Furthermore, CsA induced
      phosphorylation of extracellular regulated protein kinases 1 and 2 (ERK1/2), p38,
      and translocation of nuclear factor-kappaB (NF-kappaB) p65 in vasculature.
      Blocking ERK1/2, p38, or NF-kappaB activation with their specific inhibitors
      markedly attenuated CsA-induced upregulation of ETB receptor mRNA expression and
      protein levels, and ETB receptor-mediated contraction. In summary, this study
      showed that mitogen-activating protein kinases (ERK1/2 and p38) and the
      downstream transcriptional factor NF-kappaB pathways were involved in CsA-induced
      upregulation of ETB receptor in arterial smooth muscle cells. 

PMID- 25772259
TI  - Cytotoxic effects and degradation products of three mycotoxins: alternariol, 3
      acetyl-deoxynivalenol and 15-acetyl-deoxynivalenol in liver hepatocellular
      carcinoma cells.
AB  - This work is focused in studying the cytotoxic effects on HepG2 cells of the
      mycotoxins alternariol (AOH), 3-acetyl-deoxynivalenol (3-ADON) and 15-acetyl
      deoxynivalenol (15-ADON) by the MTT assay, as well as in the identification of
      the degradation products and/or metabolites originated after treatment by liquid
      chromatography tandem mass spectrometry (LC-MS/MS) equipment and extracted from
      culture media. HepG2 cells were treated at different concentrations over 24, 48
      and 72 h. The IC50 values were from 65 to 96 MUM, from 3.6 to 6.2 MUM and from
      5.2 to 8.1 MUM for AOH, 3-ADON and 15-ADON, respectively. Among all three
      mycotoxins assayed, deoxynivalenol (DON) derivated presented the highest toxic
      potential. Mass spectrometry (MS) scan chromatograms of studied mycotoxins
      allowed to detect products from: (i) the glutathione conjugate: (ii) sulfuric
      acid conjugated and (iii) amino group of cysteine conjugate. At all assayed
      times, the increase of recoveries values was obtained in a concentration
      dependent manner to finally decrease in the following ranking: 72 h>24h>48 h. The
      abundance relative (%) obtained for AOH's gluthathione ion product oscillated
      between 48 and 80% while for 3-ADON's ranged from 50 to 80%.

PMID- 25772260
TI  - High consumption of vegetable and fruit colour groups is inversely associated
      with the risk of colorectal cancer: a case-control study.
AB  - The colour of the edible portion of vegetables and fruit reflects the presence of
      specific micronutrients and phytochemicals. No existing studies have examined the
      relationship between the intake of vegetable and fruit colour groups and the risk
      of colorectal cancer. The present study, therefore, aimed to investigate these
      associations in a Chinese population. A case-control study was conducted between
      July 2010 and July 2014 in Guangzhou, China, in which 1057 consecutively
      recruited cases of colorectal cancer were frequency-matched to 1057 controls by
      age (5-year interval), sex and residence (rural/urban). A validated FFQ was used
      to collect dietary information during face-to-face interviews. Vegetables and
      fruit were classified into four groups according to the colour of their primarily
      edible parts: green; orange/yellow; red/purple; white. Unconditional logistic
      regression models were used to estimate the OR and 95 % CI. A higher consumption
      of orange/yellow, red/purple and white vegetables and fruit was inversely
      associated with the risk of colorectal cancer, with adjusted OR of 0.16 (95 % CI
      0.12, 0.22) for orange/yellow, 0.23 (95 % CI 0.17, 0.31) for red/purple and 0.53
      (95 % CI 0.40, 0.70) for white vegetables and fruit when the highest and lowest
      quartiles were compared. Total vegetable intake and total fruit intake have also
      been found to be inversely associated with colorectal cancer risk. However, the
      intake of green vegetable and fruit was not associated with colorectal cancer
      risk. The results of the present study, therefore, suggest that a greater intake
      of orange/yellow, red/purple and white vegetables and fruit is inversely
      associated with the risk of colorectal cancer. 

PMID- 25772261
TI  - Cadmium sulfide quantum dots induce oxidative stress and behavioral impairments
      in the marine clam Scrobicularia plana.
AB  - Cadmium sulfide (CdS) quantum dots have a number of current applications in
      electronics and solar cells and significant future potential in medicine. The aim
      of the present study was to examine the toxic effects of CdS quantum dots on the
      marine clam Scrobicularia plana exposed for 14 d to these nanomaterials (10 ug Cd
      L(-1) ) in natural seawater and to compare them with soluble Cd. Measurement of
      labile Cd released from CdS quantum dots showed that 52% of CdS quantum dots
      remained in the nanoparticulate form. Clams accumulated the same levels of Cd
      regardless of the form in which it was delivered (soluble Cd vs CdS quantum
      dots). However, significant changes in biochemical responses were observed in
      clams exposed to CdS quantum dots compared with soluble Cd. Increased activities
      of catalase and glutathione-S-transferase were significantly higher in clams
      exposed in seawater to Cd as the nanoparticulate versus the soluble form,
      suggesting a specific nano effect. The behavior of S. plana in sediment showed
      impairments of foot movements only in the case of exposure to CdS quantum dots.
      The results show that oxidative stress and behavior biomarkers are sensitive
      predictors of CdS quantum dots toxicity in S. plana. Such responses, appearing
      well before changes might occur at the population level, demonstrate the
      usefulness of this model species and type of biomarker in the assessment of
      nanoparticle contamination in estuarine ecosystems.

PMID- 25772262
TI  - Cement applicator use for hip resurfacing arthroplasty.
AB  - We compared the manufacturer recommended cementing technique for a femoral hip
      resurfacing implant (BHR, S&N) to a newly designed cement applicator on 20 porous
      carbon foam specimens. Substantial design changes and improvements of the cement
      applicator were necessary: The diameter and number of the cement escaping holes
      at the top of the applicator were optimized for medium viscosity cement. It was
      necessary to add four separate air inlet holes with large diameters. The inner
      shape of the applicator had to be adapted to the BHR design with a circular
      extending chamfer in the proximal region, a parallel inner wall and a second
      chamfer distally. The interface temperatures showed no risk for heat necrosis
      using both techniques. The cement penetration depth was more uniform and
      significantly reduced for the applicator cementing technique (4.34 +/- 1.42 mm,
      6.42 +/- 0.43 mm, p = 0.001). The cement-applicator showed no cement defects
      compared to a large defect length (0.0 +/- 0.0 mm, 10.36 +/- 1.10 mm, p < 0.001)
      with the manufacturer recommended cementing technique. The cement applicator
      technique appears to be effective for a homogenous cement distribution without
      cement defects and safe with a lower risk of polar over-penetration. 

PMID- 25772263
TI  - Catalyst free growth of ZnO nanowires on graphene and graphene oxide and its
      enhanced photoluminescence and photoresponse.
AB  - We demonstrate the graphene assisted catalyst free growth of ZnO nanowires (NWs)
      on chemical vapor deposited (CVD) and chemically processed graphene buffer layers
      at a relatively low growth temperature (580  degrees C) in the presence and
      absence of ZnO seed layers. In the case of CVD graphene covered with rapid
      thermal annealed ZnO buffer layer, the growth of vertically aligned ZnO NWs takes
      place, while the direct growth on CVD graphene, chemically derived graphene
      (graphene oxide and graphene quantum dots) without ZnO seed layer resulted in
      randomly oriented sparse ZnO NWs. Growth mechanism was studied from high
      resolution transmission electron microscopy and Raman spectroscopy of the hybrid
      structure. Further, we demonstrate strong UV, visible photoluminescence (PL) and
      enhanced photoconductivity (PC) from the CVD graphene-ZnO NWs hybrids as compared
      to the ZnO NWs grown without the graphene buffer layer. The evolution of
      crystalinity in ZnO NWs grown with ZnO seed layer and graphene buffer layer is
      correlated with the Gaussian line shape of UV and visible PL. This is further
      supported by the strong Raman mode at 438 cm(-1) significant for the wurtzite
      phase of the ZnO NWs grown on different graphene substrates. The effect of the
      thickness of ZnO seed layers and the role of graphene buffer layers on the
      aligned growth of ZnO NWs and its enhanced PC are investigated systematically.
      Our results demonstrate the catalyst free growth and superior performance of
      graphene-ZnO NW hybrid UV photodetectors as compared to the bare ZnO NW based
      photodetectors. 

PMID- 25772264
TI  - Hybrid supramolecular and colloidal hydrogels that bridge multiple length scales.
AB  - Hybrid nanocomposites were constructed based on colloidal nanofibrillar hydrogels
      with interpenetrating supramolecular hydrogels, displaying enhanced rheological
      yield strain and a synergistic improvement in storage modulus. The supramolecular
      hydrogel consists of naphthyl-functionalized hydroxyethyl cellulose and a
      cationic polystyrene derivative decorated with methylviologen moieties,
      physically cross-linked with cucurbit[8]uril macrocyclic hosts. Fast exchange
      kinetics within the supramolecular system are enabled by reversible cross-linking
      through the binding of the naphthyl and viologen guests. The colloidal hydrogel
      consists of nanofibrillated cellulose that combines a mechanically strong
      nanofiber skeleton with a lateral fibrillar diameter of a few nanometers. The two
      networks interact through hydroxyethyl cellulose adsorption to the
      nanofibrillated cellulose surfaces. This work shows methods to bridge the length
      scales of molecular and colloidal hybrid hydrogels, resulting in synergy between
      reinforcement and dynamics. 

PMID- 25772265
TI  - Abdominal pain in diabetic patients.

PMID- 25772266
TI  - The Role of Motivation in Cognitive Remediation for People with Schizophrenia.
AB  - Motivation impairment is an often prominent component of schizophrenia
      symptomatology that impacts treatment engagement and reduces the functional
      benefit from psychosocial interventions. Intrinsic motivation in particular has
      been shown to be impaired in schizophrenia. Nowhere is the role of intrinsic
      motivation impairment more evident than in cognitive remediation for
      schizophrenia. This chapter describes the theoretical determinants of motivation
      to learn and illustrates how those determinants have been translated into
      therapeutic techniques that enhance intrinsic motivation in a clinical context.
      We review the extant research that indicates how motivation enhancing techniques
      yield treatment-related improvements within cognitive remediation therapy and,
      more broadly, in other behavioral skills-based interventions for schizophrenia. 

PMID- 25772267
TI  - Adverse airway events in parturient compared with non-parturient patients. Is
      there a difference? Results from a quality management project.
AB  - AIM: The fear of airway problems often leads to prolonged attempts to obtain
      neuroaxial (spinal anesthesia or epidural anesthesia) anesthesia in obstetric
      anesthesia. The aim of this institutional quality management study was to revisit
      existing anesthesia care in the obstetric department, focusing on the frequency
      of delayed or failed neuroaxial anesthesia as well as the risk of airway problems
      in parturient and non-obstetric patients. METHODS: The clinical records from 8
      consecutive years (2005-2013) were analyzed retrospectively. Cases of cesarean
      delivery with general anesthesia were analyzed and compared with an age-matched
      group of female patients undergoing non-obstetric abdominal or gynecological
      surgery with rapid sequence induction. Poor laryngeal visualization (Cormack
      Lehane grade III or IV) and failed intubation were recorded. RESULTS: The records
      of 6393 cesarean deliveries including 851 with general anesthesia were analyzed.
      In 175 cases insufficient or delayed onset of regional anesthesia led to
      requirement for general anesthesia. The rate of poor laryngoscopic view in
      parturient women undergoing cesarean delivery was 14/851, and 4/814 in the
      reference group (P = 0.023). Failed intubation occurred in three patients
      undergoing cesarean delivery (0.4%) and in one non-obstetric patient (0.1%; P =
      0.339). CONCLUSION: The rate of failed intubations in patients undergoing
      cesarean delivery may be equivalent to non-obstetric patients. In time
      challenging cesarean deliveries, delay of conversion from non-successful
      neuroaxial anesthesia to general anesthesia in order to avoid adverse airway
      events does not appear to be justified.

PMID- 25772268
TI  - The effect of extracorporeal photopheresis alone or in combination therapy on
      circulating CD4(+) Foxp3(+) CD25(-) T cells in patients with leukemic cutaneous T
      cell lymphoma.
AB  - PURPOSE: Extracorporeal photopheresis (ECP) alone or in combination therapy is
      effective for treatment of leukemic cutaneous T-cell lymphoma (L-CTCL), but its
      mechanism(s) of action remain unclear. This study was designed to investigate the
      effect of ECP on regulatory T cells and CD8(+) T cells in L-CTCL patients.
      EXPERIMENTAL DESIGN: Peripheral blood from 18 L-CTCL patients at baseline, Day 2,
      1 month, 3 month, and 6 month post-ECP therapy was analyzed by flow cytometry for
      CD4(+) CD25(+/high) , CD4(+) Foxp3(+) CD25(+/-) , CD3(+) CD8(+) , CD3(+) CD8(+)
      CD69(+) , and CD3(+) CD8(+) IFN-gamma(+) T cells. Clinical responses were
      assessed and correlated with changes in these T-cell subsets. RESULTS: Twelve of
      18 patients achieved clinical responses. The average baseline number of CD4(+)
      CD25(+/high) T cells of PBMCs in L-CTCL patients was normal (2.2%), but increased
      at 6-month post-therapy (4.3%, P < 0.01). The average baseline number of CD4(+)
      Foxp3(+) T cells out of CD4(+) T cells in nine evaluable patients was high (66.8
      +/- 13.7%), mostly CD25 negative. The levels of CD4(+) Foxp3(+) T cells in
      responders were higher (n = 6, 93.1 +/- 5.7%) than nonresponders (n = 3, 14.2 +/-
      16.0%, P < 0.01), and they declined in parallel with malignant T cells. The
      numbers of CD3(+) CD8(+) CD69(+) and CD3(+) CD8(+) IFN-gamma(+) T cells increased
      at 3-month post-therapy in five of six patients studied. CONCLUSIONS:
      Extracorporeal photopheresis alone or in combination therapy might be effective
      in L-CTCL patients whose malignant T cells have a CD4(+) Foxp3(+) CD25(-)
      phenotype.

PMID- 25772269
TI  - Total ankle replacement for posttraumatic arthritis. Similar outcome in
      postfracture and instability arthritis: a comparison of 90 ankles.
AB  - BACKGROUND AND PURPOSE: Most studies on total ankle replacement (TAR) have used a
      case mix of patients. We evaluated the outcome of TAR performed for end-stage
      arthritis either because of fracture or ligamentous injury. PATIENTS AND METHODS:
      We prospectively followed 88 consecutive patients (50 postfracture ankles and 40
      ankles with instability arthritis (2 bilateral)) who underwent TAR between 2001
      and 2009. Mean follow-up for both groups was 5 years. RESULTS: Preoperative varus
      deformity of 10 degrees  or more was present in 23 ankles in the instability
      group. At 6 years, survival with revision or salvage fusion as an endpoint was
      87% (95% CI: 74-99) in the postfracture group and 79% (95% CI: 63-94) in the
      instability group. Progressive periprosthetic osteolysis was seen in 23 ankles,
      and required salvage fusion in 6. The number of reoperations was similar in both
      groups. Clinical outcome, as assessed with 2 ankle scores and 2 questionnaires,
      showed good results and was similar at the latest follow-up. INTERPRETATION: The
      outcome was similar in the postfracture and instability groups and also similar
      to that reported in series including a case mix of patients. In contrast to
      earlier reports, preoperative frontal plane deformity in this series was not
      identified as a risk factor for failure.

PMID- 25772270
TI  - Nurses' Experience of Maintaining Their Therapeutic Relationship With Outpatients
      With Bipolar Disorder and Their Caregivers During Different Stages of a Manic
      Episode: A Qualitative Study.
AB  - PURPOSE: Caregivers often consult community mental health (CMH) nurses when they
      recognize prodromes of mania in the outpatient. The purpose of this study was to
      determine nurses' experiences of their therapeutic relationship and nursing
      interventions to outpatients and caregivers during different stages of mania.
      DESIGN AND METHODS: A qualitative study was conducted. Nine nurses were
      interviewed. FINDINGS: CMH nurses experienced dual loyalty when facing
      conflicting interests. They strived to stay connected to patients and caregivers
      with an open and nonjudgmental attitude. In euthymic episodes, nurses anticipated
      by developing good relationships with both and by making relapse prevention plan.
      PRACTICE IMPLICATIONS: Early involvement of caregivers in the treatment is
      recommended.

PMID- 25772271
TI  - Visceral obesity determined by CT scan and outcomes after colorectal surgery; a
      systematic review and meta-analysis.
AB  - BACKGROUND: Visceral obesity may affect outcome after colorectal surgery. The
      visceral fat area as determined by CT scanning is considered the standard in the
      detection of visceral obesity. METHOD: A systematic review was performed of
      trials investigating the effect of visceral obesity on outcomes of patients with
      colorectal cancer with no radiotherapy or chemotherapy and measured by CT
      scanning. The main endpoints were primary hospital stay, morbidity, operative
      time and blood loss. Quality assessment and data extraction were performed
      independently by two observers. RESULTS: Seven studies were eligible for
      analysis, including 1230 patients. Primary hospital stay (weighted mean
      difference 1.16 days, 95% CI 0.0.05 to 2.28 days, p = 0.04), morbidity rates (RR
      0.15, 95% CI 0.10 to 0.21, p < 0.00001) and operative time (weighted mean
      difference 20.47 min, 95% CI 12.76 to 28.17 min, p < 0.00001) were significantly
      higher for visceral obese patients. No difference was found in blood loss.
      CONCLUSION: Visceral obesity leads to a longer hospital stay, higher morbidity
      and longer operative time after elective colon surgery. These findings show that
      the preoperative CT scan for detecting disseminated disease can be used to assess
      visceral obesity and helps in risk profiling patients undergoing elective colon
      surgery.

PMID- 25772272
TI  - Electrical stimulation therapy for slow transit constipation in children: a
      systematic review.
AB  - PURPOSE: Slow transit constipation is a common disorder in children, which often
      does not respond well to ordinary treatments. We have conducted a systematic
      review of reported studies in order to better define the current state of
      knowledge about electrical stimulation treatment of slow transit constipation in
      children. METHODS: We searched PubMed, Embase, Cochrane Library, BioMed Central,
      and ISI Web of Knowledge with relevant terms; six studies, all from one center,
      met the criteria for inclusion. Two trials were randomized clinical trials, and
      four were prospective studies. The number of subjects included in the studies was
      8 to 39, with ages 3 to 18 years. RESULTS: Treatment sessions varied from 20 to
      30 min 3 times per week to 1 h daily, and duration of therapy varied from 3 weeks
      to 6 months. Statistically significant improvements after electrical stimulation
      therapy were recorded in one to four outcome measures in each of the studies:
      frequency of defecation, soiling, Bristol Stool Scale, radionuclear transit
      studies, and quality of life; however, the improvements were of modest degree and
      of uncertain clinical significance. Quality assessment of the studies found
      various levels of bias, with attrition bias and reporting bias in all six.
      CONCLUSIONS: This systemic review found moderate support for the effectiveness of
      electrical stimulation therapy in slow transit constipation in children. However,
      better-designed studies, with larger and more diverse patient populations
      followed for longer time periods, will be needed in order to reliably determine
      the efficacy of electrical stimulation therapy in the treatment of this disorder.

PMID- 25772273
TI  - Vasa, PL10, and Piwi gene expression during caudal regeneration of the polychaete
      annelid Alitta virens.
AB  - Polychaetes are famous for their outstanding ability to regenerate lost body
      parts. Moreover, these worms possess a number of ancestral features in anatomy,
      development, and genetics, making them particularly suitable for comparative
      studies. Thus, fundamental as well as new undisclosed so far features of
      regenerative processes may be revealed, using polychaetes as a model. In the
      present work, we aimed to analyze the molecular basis of caudal regeneration in
      the nereid polychaete Alitta virens (formerly Nereis virens). We focused on
      homologues genes of RNA helicases Vasa and PL10 and ncRNA-binding proteins Piwi.
      These markers are suggested to play a significant role in maintenance of
      undifferentiated state of primordial germ cells and multipotent stem cells across
      invertebrates. In normal conditions, A. virens homologues of Vasa, PL10, and Piwi
      were differentially expressed in the subterminal growth zone and germline cells.
      Caudal amputation induced expression of studied genes de novo, which further
      accompanies all steps of regeneration. An early appearance of the transcripts in
      wound epithelium and internal blastemal cells suggests involvement of these genes
      in the well-known cell dedifferentiation events that assure polychaete
      regeneration. Provided interpretation of the gene expression dynamics implies the
      primary restoration of the pygidium and growth zone, which promotes following
      segment formation. Obtained results are valuable as a molecular fingerprint of
      the alterations occurring in regulatory state of locally regenerating tissues. 

PMID- 25772274
TI  - Developmental expression analysis of Na, K-ATPase alpha subunits in Xenopus.
AB  - Na, K-ATPase is an integral membrane protein complex responsible for maintaining
      the ionic gradients of Na(+) and K(+) across the plasma membrane and has a
      variety of cellular functions including neuronal activity. Studies in several
      organisms have shown that this protein complex regulates multiple aspects of
      embryonic development and is responsible for the pathogenesis of several human
      diseases. Here, we report the cloning and expression of Na, K-ATPase alpha2
      (atp1a2) and alpha3 (atp1a3) subunits during Xenopus development and compare the
      expression patterns of each subunit. Using in situ hybridization in whole embryos
      and on sections, we show that all three alpha subunits are co-expressed in the
      pronephric kidney, with varying expression in neurogenic derivatives. The atp1a2
      has a unique expression in the ependymal cell layer of the developing brain that
      is not shared with other alpha subunits. The Na, K-ATPase alpha1 (atp1a1), and
      atp1a3 share many expression domains in placode derivatives, including the otic
      vesicle, lens, ganglion of the anterodorsal lateral line nerve, and ganglia of
      the facial and anteroventral lateral line nerve and olfactory cells. All the
      subunits share a common expression domain, the myocardium. 

PMID- 25772275
TI  - Enhanced depth imaging OCT (EDI-OCT) findings in acute phase of sympathetic
      ophthalmia.
AB  - The purpose of this study was to describe the EDI-OCT findings in an acute phase
      of sympathetic ophthalmia (SO). A 24-year-old gentleman was referred to clinic
      complaining of progressive blurry vision of his right eye within last 3 days. He
      had a history of repaired corneoscleral laceration in his left eye followed by
      lensectomy and anterior vitrectomy approximately 1 month before his recent right
      eye discomfort. Physical examination revealed a granulomatous uveitis with an
      exudative RD of the right eye consistent with SO. EDI-OCT was done at initial
      exam and repeated 1 and 15 months after therapy. EDI-OCT 1 month following
      therapy showed significant improvement in choroidal thickening and outer retinal
      cell layers. The choroidal thickness in the right sympathizing eye decreased from
      617 to 568 MUm and in the left exciting eye from 539 to 521 MUm. After 15 month
      follow-up, choroidal thickness that is reported in EDI-OCT is 436 MUm in the
      right and 382 MUm in the left eye. SO should be added to the list of
      choroidopathies that cause an increase in choroidal thickness in acute phase of
      disorder with subsequent decrease after therapy, so help us in assessing and
      estimation of response to treatment.

PMID- 25772276
TI  - Three-dimensional virtual bone bank system for selecting massive bone allograft
      in orthopaedic oncology.
AB  - PURPOSE: Although structural bone allografts have been used for years to treat
      large defects caused by tumour or trauma, selecting the most appropriate
      allograft is still challenging. The objectives of this study were to: (1)
      describe the establishment of a visual bone bank system and workflow of allograft
      selection, and (2) show mid-term follow-up results of patients after allograft
      implantation. METHODS: Allografts were scanned and stored in Digital Imaging and
      Communications in Medicine (DICOM) files. Then, image segmentation was conducted
      and 3D model reconstructed to establish a visual bone bank system. Based on the
      volume registration method, allografts were selected after a careful matching
      process. From November 2010 to June 2013, with the help of the Computer-assisted
      Orthopaedic Surgery (CAOS) navigation system, the allografts were implanted in 14
      patients to fill defects after tumour resection. RESULTS: By combining the
      virtual bone bank and CAOS, selection time was reduced and matching accuracy was
      increased. After 27.5 months of follow-up, the mean Musculoskeletal Tumor Society
      (MSTS) 93 functional score was 25.7 +/- 1.1 points. Except for two patients with
      pulmonary metastases, 12 patents were alive without evidence of disease at the
      time this report was written. CONCLUSIONS: The virtual bone bank system was
      helpful for allograft selection, tumour excision and bone reconstruction, thereby
      improving the safety and effectiveness of limb-salvage surgery.

PMID- 25772277
TI  - Endoscopic gastrocnemius recession procedure using a single portal technique: a
      prospective study of fifty four consecutive patients.
AB  - BACKGROUND: Gastrocnemius recession has become a popular procedure to treat the
      equinus ankle caused by a tight gastrocnemius. The aim of our study was to
      prospectively evaluate the safety and efficacy of the endoscopic gastrocnemius
      recession procedure using a single portal technique. METHODS: The endoscopic
      gastrocnemius recession procedure was performed on 56 feet in 54 consecutive
      patients through a single lateral portal using the Smart Release Endoscopic
      Carpal Tunnel Release System. The minimum follow-up was 12 months. Functional
      outcomes were assessed with the Short Form 36 (SF-36), American Orthopaedic Foot
      and Ankle Society (AOFAS) Hindfoot score and modified Olerud and Molander (O&M)
      score. A modified Likert scale and visual analogue scores (VAS) were used to
      evaluate patient satisfaction and pain scores, respectively. Postoperative
      morbidities were documented for wound complications, scar hypersensitivity, sural
      nerve deficit and plantar flexion weakness. A p-value <0.05 was considered
      statistically significant. RESULTS: Endoscopic gastrocnemius recession procedure
      performed through a single lateral portal was successfully performed in all
      cases. Seven out of the eight component scores of the SF-36 questionnaire showed
      significant improvements. The AOFAS Hindfoot score showed a significant
      improvement of 20.69 +/- 19.20. The modified O&M score also revealed significant
      improvements in eight out of nine component scores. There was a significant
      improvement of 3.79 +/- 2.49 in VAS scores. A total of 91.07 % of all cases
      reported good or very good outcomes on the Likert scale. Eleven complications
      were recorded (three cases of unsatisfactory operative scar, three cases of sural
      nerve dysesthesia and five cases of subjective plantar flexion weakness with
      complete resolution in two out of the five patients.). CONCLUSION: This study
      demonstrates that the endoscopic gastrocnemius recession procedure performed
      through a single portal technique has low morbidity with good to excellent
      results. LEVEL OF EVIDENCE: Level III, retrospective study.

PMID- 25772278
TI  - Emergency pelvic stabilization in patients with pelvic posttraumatic instability.
AB  - INTRODUCTION: Unstable pelvic ring disruptions have been associated with high
      rates of morbidity. Accurate reduction with fixation diminishes pain, permits
      early patient mobility, and allows the pelvic ring to improve functional outcome.
      MATERIAL AND METHODS: This was a retrospective study, whereby 30 polytrauma
      hospitalized patients were included, with unstable pelvic lesions stabilized with
      an external fixator as a mean of temporary or definitive fixation. Data collected
      for these sample were: age, sex, cause of trauma, type of pelvic lesion,
      associated lesions (ISS score), pelvic stabilization methods, and functional
      outcome. There were 17 male subjects (57%) and 13 female subjects (43%), with a
      mean age of 42.5 years (range 18-62 years). According to Tile classification, the
      unstable pelvic ring lesions prevailed; 60 % of patients were type C while three
      patients with type C instability had associated acetabular fractures, and 40% had
      type B rotational instability. Stabilization was achieved using an external
      fixator in 16 patients; in 14 patients the anterior ring fixation was used with
      an external fixator combined with posterior stabilization using percutaneous
      sacroiliac screws. The pelvic stabilization using the external fixator was later
      replaced with plates and screws (ORIF) in four patients. Follow-up at one, three,
      six and 12 months postoperatively was based on the Majeed functional score and
      radiographic assessment. RESULTS: Eighteen patients (78%) had an excellent Majeed
      functional score, four patients had a good score, and only one patient had a fair
      functional outcome. Malunions were recorded in four patients with Tile C that
      were stabilized only by external fixation, and superficial pin track infection
      occurred in three patients. Within the studied group seven deaths have been
      recorded (23%) in patients with extremely severe associated injuries (ISS over
      50), this being the decisive factor that determined the unfavourable evolution in
      six patients. CONCLUSIONS: The external fixation stabilizes the anterior pelvic
      ring lesions and it can be combined with the posterior stabilization using
      percutaneous sacro-iliac screws in case of associated lesions of the posterior
      ring. The external fixator is very useful especially in the acute phase,
      acquiring an acceptable reduction and an adequate stability in the partially
      unstable lesions (Tile B) and also reduces the pelvic volume and bleeding, being
      considered essential within the resuscitation protocols. The external fixator can
      be used as a permanent stabilization method when it guarantees a satisfying
      reduction.

PMID- 25772279
TI  - Biological aspects of segmental bone defects management.
AB  - Segmental bone defect management is among the most demanding issues in
      orthopaedics and there is a great medical need for establishing an appropriate
      treatment option. Tissue transfer, including bone autografts or free flaps,
      depending on the size of the bone deficiency, is currently the "gold standard"
      for treatment of such defects. Osteogenic cells in combination with adequate
      growth factors and a suitable scaffold, from the aspect of osteoinductivity,
      osteoconductivity and mechanical stability, are mandatory to successfully restore
      a bone defect as determined in the "diamond concept". Our current knowledge on
      this topic is limited and mostly based on retrospective studies, case reports and
      a few small randomised clinical trials due to the lack of large and accurately
      designed randomised clinical trials using novel approaches to regenerative
      orthopaedics. However, preclinical research on different animal models for
      critical size defects is abundant, showing emerging candidate cells and cytokines
      for defect rebridgement. In this article we provide an overview on existing
      clinical studies and promising preclinical experiments that utilised osteogenic
      cells, growth factors and biomaterials, as well as their combination for repair
      of segmental bone defects. 

PMID- 25772280
TI  - Impact of prior intracoronary stenting on late outcomes of coronary artery bypass
      surgery in diabetics with triple-vessel disease.
AB  - OBJECTIVE: Recent studies have indicated that coronary artery bypass grafting
      (CABG) outcomes in patients with prior stents are suboptimal. We aimed to study
      the impact of prior percutaneous coronary intervention (PCI) with stenting (PCI
      S) on late CABG mortality in diabetic patients with triple-vessel disease.
      METHODS: We reviewed the primary nonemergency CABG experience from a single U.S.
      institution (n = 7005; 1996-2007, Toledo, Ohio). Diabetics with triple-vessel
      disease (n = 1583) were identified and divided into 2 groups: (1) prior PCI-S (n
      = 202); and (2) no prior PCI (No-PCI [n = 1381]). Hierarchic Cox proportional
      hazards models were used to assess the effect of prior PCI-S on 5-year mortality
      after CABG. A propensity score for PCI-S and No-PCI patients was derived using a
      nonparsimonious logistic regression and used to generate a 1:1 (PCI-S to No-PCI)
      matched cohort. RESULTS: In model 1, after adjusting for preoperative clinical
      characteristics, medications, off-pump surgery, and isolated CABG surgery status,
      prior PCI-S was associated with a 39% increased risk of mortality (hazard ratio
      [HR] = 1.39, with 95% confidence interval [CI; 1.02, 1.90]; P = .04). Further
      adjustment for date of surgery (model 2) (HR = 1.39, with 95% CI [1.02, 1.91]; P
      = .04) or operative parameters (model 3) (HR = 1.38, with 95% CI [1.01, 1.88]; P
      = .046) did not alter the association. The 1:1 matched-cohort analysis confirmed
      the increased risk associated with PCI-S (HR = 1.61, with 95% CI [1.03, 2.51]; P
      = .037). CONCLUSIONS: Patients who have both diabetes and triple-vessel disease,
      and have undergone prior PCI-S, have poorer long-term outcomes after CABG
      compared with those who have had no prior PCI-S.

PMID- 25772281
TI  - Updated patterns of failure after multimodality therapy for malignant pleural
      mesothelioma.
AB  - OBJECTIVE: We have previously described patterns of failure after extrapleural
      pneumonectomy and multimodality therapy for malignant pleural mesothelioma and
      sought to update our results with a larger cohort of recent patients. METHODS: A
      total of 169 patients underwent extrapleural pneumonectomy without preoperative
      chemotherapy between 2001 and 2010. Data for treatment, recurrence, and survival
      were determined from medical records. A thoracic radiologist reviewed
      postoperative computed tomography or positron emission tomography computed
      tomography scans to determine sites of recurrence. Time to recurrence was
      estimated by the Kaplan-Meier method. Rates were compared using the Fisher exact
      test. RESULTS: The median age of patients was 62 years. Histology on final
      pathology was epithelial for 104 patients (62%) and nonepithelial for 65 patients
      (38%). A total of 132 patients (78%) received heated intraoperative chemotherapy;
      77 patients (45%) received adjuvant chemotherapy, and 71 patients (42%) received
      adjuvant radiation therapy. Most chemotherapy regimens included platinum or
      pemetrexed. Median radiation therapy dose was 54 Gy. Among 158 evaluable
      patients, a recurrence developed in 118 (75%). Median follow-up was 83 months,
      median time to recurrence was 13.1 months, and median survival was 15 months.
      Sites of first recurrence were in the ipsilateral hemithorax or mediastinum for
      54% of patients, in the abdomen for 39% of patients, in the contralateral
      hemithorax for 28% of patients, and in other distant sites for 5% of patients.
      Some patients had simultaneous recurrences in multiple sites. CONCLUSIONS: The
      most common site of recurrence after extrapleural pneumonectomy and planned
      multimodality therapy remains the ipsilateral hemithorax (including mediastinum),
      and true distant failure (other than the abdomen or contralateral hemithorax)
      remains unusual. The distribution of recurrences is strikingly similar to our
      prior report.

PMID- 25772283
TI  - The Hsp60 peptide p277 enhances anti-CD3 mediated diabetes remission in non-obese
      diabetic mice.
AB  - Type 1 diabetes (T1D) is characterized by the immune-mediated destruction of
      pancreatic beta cells leading to inadequate glycemic control. Trials with
      immunomodulatory monotherapies have shown that the disease course can in
      principle be altered. The observed preservation of endogenous insulin secretion
      however is typically transient and chronic treatment is often associated with
      significant side effects. Here we combined anti-CD3 with the Hsp60 peptide p277,
      two drugs that have been evaluated in Phase 3 trials, to test for enhanced
      efficacy. Female NOD mice with recent onset diabetes were given 5 MUg anti-CD3
      i.v., on three consecutive days in combination with 100 MUg of p277 peptide in
      IFA s.c., once weekly for four weeks. Anti-CD3 alone restored normoglycemia in
      44% of the mice while combination therapy with anti-CD3 and p277 induced stable
      remission in 83% of mice. The observed increase in protection occurred only in
      part through TLR2 signaling and was characterized by increased Treg numbers and
      decreased insulitis. These results have important implications for the design of
      combination therapies for the treatment of T1D. 

PMID- 25772284
TI  - Influence of yogurt fermentation and refrigerated storage on the stability of
      protein toxin contaminants.
AB  - Dairy products sold in a ready-to-eat form present the risk that adulterants
      persisting through manufacturing, storage, and distribution would reach
      consumers. Pathogenic microbes, including shigatoxigenic strains of Escherichia
      coli and the toxins they produce, are common food safety hazards associated with
      dairy products. Ricin and abrin are plant-derived ribosome-inactivating protein
      toxins related to the shiga-like toxins produced by E. coli. Limited information
      exists on the effects of manufacturing processes on the stabilities of these heat
      resistant ribosome-inactivating proteins in the presence of foods. The goal of
      this study was to determine how typical yogurt manufacturing and storage
      processes influence ribosome-inactivating protein toxins. Ricin and abrin were
      added to skim or whole milk and batch pasteurized. Complete inactivation of both
      toxins was observed after 30 minutes at 85  degrees C. If the toxins were added
      after pasteurization, the levels of ricin and abrin in yogurt and their cytotoxic
      activities did not change significantly during fermentation or refrigerated
      storage for 4 weeks. The activities of ricin and abrin were inhibited by skim
      milk, nonfat yogurt, whole milk, and whole milk yogurt. The results showed
      minimal effects of the toxins on yogurt pH and %titratable acidity but inhibitory
      effects of yogurt on toxin activity. 

PMID- 25772285
TI  - Candida parapsilosis Tenosynovitis in an Immunocompetent Patient: Case Report and
      Review of Literature.
AB  - We describe a case of fungal tenosynovitis with Candida parapsilosis, which is an
      uncommonly reported agent causing tenosynovitis. It occurred in an
      immunocompetent individual, and the patient underwent an extensive noninfectious
      work-up for ongoing swelling and stiffness before being correctly diagnosed and
      treated. We emphasize the importance of considering atypical infections in the
      differential diagnoses in a patient presenting with indolent symptoms of
      tenosynovitis. 

PMID- 25772286
TI  - Predicting alignment after closed reduction and casting of distal radius
      fractures.
AB  - PURPOSE: We sought to independently validate the McQueen equation and
      LaFontaine's criteria as predictors of instability in a large series of distal
      radius fractures treated nonsurgically. In addition, we hypothesized that
      restoring the volar cortical integrity (ie, volar hook) would be another factor
      that would independently predict the maintenance of a closed reduction in a cast.
      METHODS: We screened 546 consecutive distal radius fractures with 168 meeting all
      inclusion criteria. Dorsal tilt, radial height, radial inclination, ulnar
      variance, and carpal malalignment were measured on initial postreduction and
      final radiographs. A univariate analysis evaluated the predictability of the
      McQueen equation, Lafontaine's criteria, and volar hook on each radiographic
      parameter. A multivariate analysis was performed using the significant results
      from the univariate analysis. RESULTS: In the univariate analysis, the McQueen
      formula, the number of Lafontaine criteria, and age all correlated with radial
      height, radial inclination, and ulnar variance. In the multivariate analysis, age
      correlated with the most radiographic factors including radial height, radial
      inclination, ulnar variance, and carpal alignment at healing. Volar hook
      correlated with dorsal tilt and carpal alignment at healing, and dorsal
      comminution correlated with dorsal tilt. CONCLUSIONS: In the nonsurgical
      treatment of distal radius fractures, we were able to validate the McQueen
      equation and Lafontaine's criteria in predicting the final radial height and
      inclination and final ulnar variance. Neither method was predictive of final
      dorsal tilt or carpal malalignment. However, restoring volar cortical continuity
      by hooking the volar cortex in the initial reduction proved to be the strongest
      predictor of final volar tilt, the change in volar tilt, and carpal malalignment
      at union. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic III.

PMID- 25772287
TI  - David Yue (1957-2014).

PMID- 25772288
TI  - Sodium and calcium regulation in cardiac myocytes: from molecules to heart
      failure and arrhythmia.

PMID- 25772289
TI  - Deranged sodium to sudden death.
AB  - In February 2014, a group of scientists convened as part of the University of
      California Davis Cardiovascular Symposium to bring together experimental and
      mathematical modelling perspectives and discuss points of consensus and
      controversy on the topic of sodium in the heart. This paper summarizes the topics
      of presentation and discussion from the symposium, with a focus on the role of
      aberrant sodium channels and abnormal sodium homeostasis in cardiac arrhythmias
      and pharmacotherapy from the subcellular scale to the whole heart. Two following
      papers focus on Na(+) channel structure, function and regulation, and
      Na(+)/Ca(2+) exchange and Na(+)/K(+) ATPase. The UC Davis Cardiovascular
      Symposium is a biannual event that aims to bring together leading experts in
      subfields of cardiovascular biomedicine to focus on topics of importance to the
      field. The focus on Na(+) in the 2014 symposium stemmed from the multitude of
      recent studies that point to the importance of maintaining Na(+) homeostasis in
      the heart, as disruption of homeostatic processes are increasingly identified in
      cardiac disease states. Understanding how disruption in cardiac Na(+)-based
      processes leads to derangement in multiple cardiac components at the level of the
      cell and to then connect these perturbations to emergent behaviour in the heart
      to cause disease is a critical area of research. The ubiquity of disruption of
      Na(+) channels and Na(+) homeostasis in cardiac disorders of excitability and
      mechanics emphasizes the importance of a fundamental understanding of the
      associated mechanisms and disease processes to ultimately reveal new targets for
      human therapy.

PMID- 25772290
TI  - Na+ channel function, regulation, structure, trafficking and sequestration.
AB  - This paper is the second of a series of three reviews published in this issue
      resulting from the University of California Davis Cardiovascular Symposium 2014:
      Systems approach to understanding cardiac excitation-contraction coupling and
      arrhythmias: Na(+) channel and Na(+) transport. The goal of the symposium was to
      bring together experts in the field to discuss points of consensus and
      controversy on the topic of sodium in the heart. The present review focuses on
      Na(+) channel function and regulation, Na(+) channel structure and function, and
      Na(+) channel trafficking, sequestration and complexing. 

PMID- 25772292
TI  - A leap(frog) forward in understanding focal arrhythmia.

PMID- 25772293
TI  - IP3 and Ca(2+) signals in the heart: boost them or bust them?

PMID- 25772294
TI  - Palpitations, potassium and the pump.

PMID- 25772291
TI  - Na+/Ca2+ exchange and Na+/K+-ATPase in the heart.
AB  - This paper is the third in a series of reviews published in this issue resulting
      from the University of California Davis Cardiovascular Symposium 2014: Systems
      approach to understanding cardiac excitation-contraction coupling and
      arrhythmias: Na(+) channel and Na(+) transport. The goal of the symposium was to
      bring together experts in the field to discuss points of consensus and
      controversy on the topic of sodium in the heart. The present review focuses on
      cardiac Na(+)/Ca(2+) exchange (NCX) and Na(+)/K(+)-ATPase (NKA). While the
      relevance of Ca(2+) homeostasis in cardiac function has been extensively
      investigated, the role of Na(+) regulation in shaping heart function is often
      overlooked. Small changes in the cytoplasmic Na(+) content have multiple effects
      on the heart by influencing intracellular Ca(2+) and pH levels thereby modulating
      heart contractility. Therefore it is essential for heart cells to maintain Na(+)
      homeostasis. Among the proteins that accomplish this task are the Na(+)/Ca(2+)
      exchanger (NCX) and the Na(+)/K(+) pump (NKA). By transporting three Na(+) ions
      into the cytoplasm in exchange for one Ca(2+) moved out, NCX is one of the main
      Na(+) influx mechanisms in cardiomyocytes. Acting in the opposite direction, NKA
      moves Na(+) ions from the cytoplasm to the extracellular space against their
      gradient by utilizing the energy released from ATP hydrolysis. A fine balance
      between these two processes controls the net amount of intracellular Na(+) and
      aberrations in either of these two systems can have a large impact on cardiac
      contractility. Due to the relevant role of these two proteins in Na(+)
      homeostasis, the emphasis of this review is on recent developments regarding the
      cardiac Na(+)/Ca(2+) exchanger (NCX1) and Na(+)/K(+) pump and the controversies
      that still persist in the field.

PMID- 25772295
TI  - Scn1b deletion leads to increased tetrodotoxin-sensitive sodium current, altered
      intracellular calcium homeostasis and arrhythmias in murine hearts.
AB  - KEY POINTS: Na(+) current (INa) results from the integrated function of a
      molecular aggregate (the voltage-gated Na(+) channel complex) that includes the
      beta subunit family. Mutations or rare variants in Scn1b (encoding the beta1 and
      beta1B subunits) have been associated with various inherited arrhythmogenic
      syndromes, including Brugada syndrome and sudden unexpected death in patients
      with epilepsy. We used Scn1b null mice to understand better the relation between
      Scn1b expression, and cardiac electrical function. Loss of Scn1b caused, among
      other effects, increased amplitude of tetrodotoxin-sensitive INa, delayed after
      depolarizations, triggered beats, delayed Ca(2+) transients, frequent spontaneous
      calcium release events and increased susceptibility to polymorphic ventricular
      arrhythmias. Most alterations in Ca(2+) homeostasis were prevented by 100 nM
      tetrodotoxin. We propose that life-threatening arrhythmias in patients with
      mutations in Scn1b, a gene classically defined as ancillary to the Na(+) channel
      alpha subunit, can be partly consequent to disrupted intracellular Ca(2+)
      homeostasis. ABSTRACT: Na(+) current (INa) is determined not only by the
      properties of the pore-forming voltage-gated Na(+) channel (VGSC) alpha subunit,
      but also by the integrated function of a molecular aggregate (the VGSC complex)
      that includes the VGSC beta subunit family. Mutations or rare variants in Scn1b
      (encoding the beta1 and beta1B subunits) have been associated with various
      inherited arrhythmogenic syndromes, including cases of Brugada syndrome and
      sudden unexpected death in patients with epilepsy. Here, we have used Scn1b null
      mouse models to understand better the relation between Scn1b expression, and
      cardiac electrical function. Using a combination of macropatch and scanning ion
      conductance microscopy we show that loss of Scn1b in juvenile null animals
      resulted in increased tetrodotoxin-sensitive INa but only in the cell midsection,
      even before full T-tubule formation; the latter occurred concurrent with
      increased message abundance for the neuronal Scn3a mRNA, suggesting increased
      abundance of tetrodotoxin-sensitive NaV 1.3 protein and yet its exclusion from
      the region of the intercalated disc. Ventricular myocytes from cardiac-specific
      adult Scn1b null animals showed increased Scn3a message, prolonged action
      potential repolarization, presence of delayed after-depolarizations and triggered
      beats, delayed Ca(2+) transients and frequent spontaneous Ca(2+) release events
      and at the whole heart level, increased susceptibility to polymorphic ventricular
      arrhythmias. Most alterations in Ca(2+) homeostasis were prevented by 100 nM
      tetrodotoxin. Our results suggest that life-threatening arrhythmias in patients
      with mutations in Scn1b, a gene classically defined as ancillary to the Na(+)
      channel alpha subunit, can be partly consequent to disrupted intracellular Ca(2+)
      homeostasis in ventricular myocytes.

PMID- 25772296
TI  - Contribution of sodium channel neuronal isoform Nav1.1 to late sodium current in
      ventricular myocytes from failing hearts.
AB  - KEY POINTS: Late Na(+) current (INaL) contributes to action potential remodelling
      and Ca(2+)/Na(+) changes in heart failure. The molecular identity of INaL remains
      unclear. The contributions of different Na(+) channel isoforms, apart from the
      cardiac isoform, remain unknown. We discovered and characterized a substantial
      contribution of neuronal isoform Nav1.1 to INaL. This new component is
      physiologically relevant to the control of action potential shape and duration,
      as well as to cell Ca(2+) dynamics, especially in heart failure. ABSTRACT: Late
      Na(+) current (INaL) contributes to action potential (AP) duration and Ca(2+)
      handling in cardiac cells. Augmented INaL was implicated in delayed
      repolarization and impaired Ca(2+) handling in heart failure (HF). We tested if
      Na(+) channel (Nav) neuronal isoforms contribute to INaL and Ca(2+) cycling
      defects in HF in 17 dogs in which HF was achieved via sequential coronary artery
      embolizations. Six normal dogs served as control. Transient Na(+) current (INaT )
      and INaL in left ventricular cardiomyocytes (VCMs) were recorded by patch clamp
      while Ca(2+) dynamics was monitored using Fluo-4. Virally delivered short
      interfering RNA (siRNA) ensured Nav1.1 and Nav1.5 post-transcriptional silencing.
      The expression of six Navs was observed in failing VCMs as follows: Nav1.5
      (57.3%) > Nav1.2 (15.3%) > Nav1.1 (11.6%) > Nav2.1 (10.7%) > Nav1.3 (4.6%) >
      Nav1.6 (0.5%). Failing VCMs showed up-regulation of Nav1.1 expression, but
      reduction of Nav1.6 mRNA. A similar Nav expression pattern was found in samples
      from human hearts with ischaemic HF. VCMs with silenced Nav1.5 exhibited residual
      INaT and INaL (~30% of control) with rightwardly shifted steady-state activation
      and inactivation. These currents were tetrodotoxin sensitive but resistant to
      MTSEA, a specific Nav1.5 blocker. The amplitude of the tetrodotoxin-sensitive
      INaL was 0.1709 +/- 0.0299 pA pF(-1) (n = 7 cells) and the decay time constant
      was tau = 790 +/- 76 ms (n = 5). This INaL component was lacking in VCMs with a
      silenced Nav1.1 gene, indicating that, among neuronal isoforms, Nav1.1 provides
      the largest contribution to INaL. At -10 mV this contribution is ~60% of total
      INaL. Our further experimental and in silico examinations showed that this new
      Nav1.1 INaL component contributes to Ca(2+) accumulation in failing VCMs and
      modulates AP shape and duration. In conclusion, we have discovered an Nav1.1
      originated INaL component in dog heart ventricular cells. This component is
      physiologically relevant to controlling AP shape and duration, as well as to cell
      Ca(2+) dynamics.

PMID- 25772297
TI  - Decreased inward rectifying K+ current and increased ryanodine receptor
      sensitivity synergistically contribute to sustained focal arrhythmia in the
      intact rabbit heart.
AB  - KEY POINTS: Heart failure leads to dramatic electrophysiological remodelling as a
      result of numerous cellular and tissue-level changes. Important cellular changes
      include increased sensitivity of ryanodine receptors (RyRs) to Ca(2+) release and
      down-regulation of the inward rectifying K(+) current (IK1), both of which
      contribute to triggered action potentials in isolated cells. We studied the role
      of increased RyR sensitivity and decreased IK1 in contributing to focal
      arrhythmia in the intact non-failing rabbit heart using optical mapping and
      pharmacological manipulation of RyRs and IK1. Neither increased RyR sensitivity
      or decreased IK1 alone led to significant increases in arrhythmia following local
      sympathetic stimulation; however, in combination, these two factors led to a
      significant increase in premature ventricular complexes and focal ventricular
      tachycardia. These results suggest synergism between increased RyR sensitivity
      and decreased IK1 in contributing to focal arrhythmia in the intact heart and may
      provide important insights into novel anti-arrhythmic treatments in heart
      failure. ABSTRACT: Heart failure (HF) results in dramatic electrophysiological
      remodelling, including increased sensitivity of ryanodine receptors (RyRs) and
      decreased inward rectifying K(+) current (IK1), which predisposes HF myocytes to
      delayed afterdepolarizations and triggered activity. Therefore, we sought to
      determine the role of increased RyR sensitivity and decreased IK1 in contributing
      to focal arrhythmia in the intact non-failing heart. Optical mapping of
      transmembrane potential and intracellular Ca(2+) was performed in Langendorff
      perfused rabbit hearts (n = 15). Local beta-adrenergic receptor stimulation with
      noradrenaline (norepinephrine; NA, 50 MUl, 250 MUM) was applied to elicit focal
      activity (premature ventricular complexes (PVCs) or ventricular tachycardia (VT
      >= 3 beats)). NA was administered under control conditions (CTL) and following
      pretreatment with 50 MUM BaCl2 to reduce IK1, or 200 MUM caffeine (Caff) to
      sensitize RyRs, both alone and in combination. Local NA injection resulted in
      Ca(2+)-driven PVCs arising from the injection site in all hearts studied. No
      increase in NA-mediated PVCs was observed following pretreatment with either
      BaCl2 or Caff alone (CTL: 1.1 +/- 0.7, BaCl2: 1.0 +/- 0.7, Caff: 1.3 +/- 0.8
      PVCs/injection, P not significant). However, pretreatment with the combination of
      BaCl2 + Caff resulted in a significant increase in PVCs (2.3 +/- 2.8
      PVCs/injection, P < 0.05 vs. CTL, BaCl2, Caff). Additionally, pretreatment with
      BaCl2 + Caff led to sustained monomorphic VT arising from the NA application site
      in all hearts studied, which lasted up to 6 min following a single NA injection.
      VT was never observed under any other condition suggesting synergism between
      increased RyR sensitivity and decreased IK1 in contributing to focal activity.
      These findings may have important implications for the understanding and
      prevention of focal arrhythmia in HF.

PMID- 25772298
TI  - Maximal acceleration of Ca2+ release refractoriness by beta-adrenergic
      stimulation requires dual activation of kinases PKA and CaMKII in mouse
      ventricular myocytes.
AB  - KEY POINTS: Refractoriness of calcium release in heart cells is altered in
      several disease states, but the physiological mechanisms that regulate this
      process are incompletely understood. We examined refractoriness of calcium
      release in mouse ventricular myocytes and investigated how activation of
      different intracellular signalling pathways influenced this process. We found
      that refractoriness of calcium release is abbreviated by stimulation of the
      'fight-or-flight' response, and that simultaneous activation of multiple
      intracellular signalling pathways contributes to this response. Data obtained
      under several conditions at the subcellular, microscopic level were consistent
      with results obtained at the cellular level. The results provide insight into
      regulation of cardiac calcium release and how alterations to this process may
      increase arrhythmia risk under different conditions. ABSTRACT: Time-dependent
      refractoriness of calcium (Ca(2+)) release in cardiac myocytes is an important
      factor in determining whether pro-arrhythmic release patterns develop. At the
      subcellular level of the Ca(2+) spark, recent studies have suggested that
      recovery of spark amplitude is controlled by local sarcoplasmic reticulum (SR)
      refilling whereas refractoriness of spark triggering depends on both refilling
      and the sensitivity of the ryanodine receptor (RyR) release channels that produce
      sparks. Here we studied regulation of Ca(2+) spark refractoriness in mouse
      ventricular myocytes by examining how beta-adrenergic stimulation influenced
      sequences of Ca(2+) sparks originating from individual RyR clusters. Our protocol
      allowed us to separately measure recovery of spark amplitude and delays between
      successive sparks, and data were interpreted quantitatively through simulations
      with a stochastic mathematical model. We found that, compared with spark
      sequences measured under control conditions: (1) beta-adrenergic stimulation with
      isoproterenol (isoprenaline) accelerated spark amplitude recovery and decreased
      spark-to-spark delays; (2) activating protein kinase A (PKA) with forskolin
      accelerated amplitude recovery but did not affect spark-to-spark delays; (3)
      inhibiting PKA with H89 retarded amplitude recovery and increased spark-to-spark
      delays; (4) preventing phosphorylation of the RyR at serine 2808 with a knock-in
      mouse prevented the decrease in spark-to-spark delays seen with beta-adrenergic
      stimulation; (5) inhibiting either PKA or Ca(2+)/calmodulin-dependent protein
      kinase II (CaMKII) during beta-adrenergic stimulation prevented the decrease in
      spark-to-spark delays seen without inhibition. The results suggest that
      activation of either PKA or CaMKII is sufficient to speed SR refilling, but
      activation of both kinases appears necessary to observe increased RyR
      sensitivity. The data provide novel insight into beta-adrenergic regulation of
      Ca(2+) release refractoriness in mouse myocytes.

PMID- 25772299
TI  - Hypokalaemia induces Ca2+ overload and Ca2+ waves in ventricular myocytes by
      reducing Na+,K+-ATPase alpha2 activity.
AB  - KEY POINTS: Hypokalaemia is a risk factor for development of ventricular
      arrhythmias. In rat ventricular myocytes, low extracellular K(+) (corresponding
      to clinical moderate hypokalaemia) increased Ca(2+) wave probability, Ca(2+)
      transient amplitude, sarcoplasmic reticulum (SR) Ca(2+) load and induced SR
      Ca(2+) leak. Low extracellular K(+) reduced Na(+),K(+)-ATPase (NKA) activity and
      hyperpolarized the resting membrane potential in ventricular myocytes. Both
      experimental data and modelling indicate that reduced NKA activity and subsequent
      Na(+) accumulation sensed by the Na(+), Ca(2+) exchanger (NCX) lead to increased
      Ca(2+) transient amplitude despite concomitant hyperpolarization of the resting
      membrane potential. Low extracellular K(+) induced Ca(2+) overload by lowering
      NKA alpha2 activity. Triggered ventricular arrhythmias in patients with
      hypokalaemia may therefore be attributed to reduced NCX forward mode activity
      linked to an effect on the NKA alpha2 isoform. ABSTRACT: Hypokalaemia is a risk
      factor for development of ventricular arrhythmias. The aim of this study was to
      determine the cellular mechanisms leading to triggering of arrhythmias in
      ventricular myocytes exposed to low Ko. Low Ko, corresponding to moderate
      hypokalaemia, increased Ca(2+) transient amplitude, sarcoplasmic reticulum (SR)
      Ca(2+) load, SR Ca(2+) leak and Ca(2+) wave probability in field stimulated rat
      ventricular myocytes. The mechanisms leading to Ca(2+) overload were examined.
      Low Ko reduced Na(+),K(+)-ATPase (NKA) currents, increased cytosolic Na(+)
      concentration and increased the Na(+) level sensed by the Na(+), Ca(2+) exchanger
      (NCX). Low Ko also hyperpolarized the resting membrane potential (RMP) without
      significant alterations in action potential duration. Experiments in voltage
      clamped and field stimulated ventricular myocytes, along with mathematical
      modelling, suggested that low Ko increases the Ca(2+) transient amplitude by
      reducing NKA activity despite hyperpolarization of the RMP. Selective inhibition
      of the NKA alpha2 isoform by low dose ouabain abolished the ability of low Ko to
      reduce NKA currents, to increase Na(+) levels sensed by NCX and to increase the
      Ca(2+) transient amplitude. We conclude that low Ko, within the range of moderate
      hypokalaemia, increases Ca(2+) levels in ventricular myocytes by reducing the
      pumping rate of the NKA alpha2 isoform with subsequent Na(+) accumulation sensed
      by the NCX. These data highlight reduced NKA alpha2 -mediated control of NCX
      activity as a possible mechanism underlying triggered ventricular arrhythmias in
      patients with hypokalaemia.

PMID- 25772300
TI  - Universality of fragment shapes.
AB  - The shape of fragments generated by the breakup of solids is central to a wide
      variety of problems ranging from the geomorphic evolution of boulders to the
      accumulation of space debris orbiting Earth. Although the statistics of the mass
      of fragments has been found to show a universal scaling behavior, the
      comprehensive characterization of fragment shapes still remained a fundamental
      challenge. We performed a thorough experimental study of the problem fragmenting
      various types of materials by slowly proceeding weathering and by rapid breakup
      due to explosion and hammering. We demonstrate that the shape of fragments obeys
      an astonishing universality having the same generic evolution with the fragment
      size irrespective of materials details and loading conditions. There exists a
      cutoff size below which fragments have an isotropic shape, however, as the size
      increases an exponential convergence is obtained to a unique elongated form. We
      show that a discrete stochastic model of fragmentation reproduces both the size
      and shape of fragments tuning only a single parameter which strengthens the
      general validity of the scaling laws. The dependence of the probability of the
      crack plan orientation on the linear extension of fragments proved to be
      essential for the shape selection mechanism. 

PMID- 25772302
TI  - Prevalence, diversity and characterization of enterococci from three coraciiform
      birds.
AB  - Coraciiform birds hoopoe (Upupa epops), common kingfisher (Alcedo atthis) and
      European roller (Coracius garrulus) were examined for enterococci in their
      cloacae and uropygial glands. The enterococcal isolates were identified at the
      species level using several genomic and proteomic methods, screened for
      antibiotic susceptibility and genotyped by pulsed-field gel electrophoresis
      (PFGE). Clonality of isolates from the common kingfisher was also assessed by
      multi-locus sequence typing (MLST). Using selective media, putative enterococcal
      isolates (n = 117) were recovered from 74% (32 out of a total of 43) of the bird
      samples and 114 isolates were confirmed as enterococci. Overall, among the total
      of 6 different species detected, Enterococcus faecalis was dominant (59%) in all
      three bird species. The second most frequently isolated species was Enterococcus
      casseliflavus (32%). PFGE revealed great diversity of strains from different bird
      species and anatomic location. Closely related strains were found only from
      nestlings from the same nest. No genes conferring resistance to vancomycin (vanA,
      vanB, vanC1 and van C2/C3) or erythromycin (erm A, ermB and mefA/E) were
      detected. MLST analysis and eBURST clustering revealed that sequence types of E.
      faecalis from the common kingfisher were identical to those of isolates found
      previously in water, chickens, and humans.

PMID- 25772301
TI  - New insight into the structure and function of Hfq C-terminus.
AB  - Accumulating evidence indicates that RNA metabolism components assemble into
      supramolecular cellular structures to mediate functional compartmentalization
      within the cytoplasmic membrane of the bacterial cell. This cellular
      compartmentalization could play important roles in the processes of RNA
      degradation and maturation. These components include Hfq, the RNA chaperone
      protein, which is involved in the post-transcriptional control of protein
      synthesis mainly by the virtue of its interactions with several small regulatory
      ncRNAs (sRNA). The Escherichia coli Hfq is structurally organized into two
      domains. An N-terminal domain that folds as strongly bent beta-sheets within
      individual protomers to assemble into a typical toroidal hexameric ring. A C
      terminal flexible domain that encompasses approximately one-third of the protein
      seems intrinsically unstructured. RNA-binding function of Hfq mainly lies within
      its N-terminal core, whereas the function of the flexible domain remains
      controversial and largely unknown. In the present study, we demonstrate that the
      Hfq-C-terminal region (CTR) has an intrinsic property to self-assemble into long
      amyloid-like fibrillar structures in vitro. We show that normal localization of
      Hfq within membrane-associated coiled structures in vivo requires this C-terminal
      domain. This finding establishes for the first time a function for the hitherto
      puzzling CTR, with a plausible central role in RNA transactions.

PMID- 25772303
TI  - Fontibacillus solani sp. nov. isolated from potato (Solanum tuberosum L.) root.
AB  - A bacterial strain designated A4STR04(T) was isolated from the inner root tissue
      of potatoes in Spain. Phylogenetic analysis based on the 16S rRNA gene sequence
      placed the isolate into the genus Fontibacillus, being most closely related to
      Fontibacillus panacisegetis KCTC 13564(T) with 99% identity. The isolate was
      observed to form Gram-positive, motile and sporulating rods. The catalase test
      was found to be negative and oxidase positive. Nitrate was found to be reduced to
      nitrite. beta-Galactosidase and caseinase were observed to be produced but the
      production of gelatinase, urease, arginine dehydrolase, ornithine and lysine
      decarboxylase was negative. Aesculin hydrolysis was found to be positive and
      acetoin production was negative. Growth was found to be supported by many
      carbohydrates and organic acids as carbon source. MK-7 was the only menaquinone
      detected and the major fatty acid (61.5%) was identified as anteiso-C(15:0), as
      occurs in the other species of genus Fontibacillus. The strain A4STR04(T) was
      found to display a complex lipid profile consisting of diphosphatidylglycerol,
      phosphatidylglycerol, phosphatidylethanolamine, a glycolipid, two phospholipids,
      a lipid and two aminophospholipids. Mesodiaminopimelic acid was detected in the
      peptidoglycan. The G+C content was determined to be 50.5 mol% (Tm). Phylogenetic,
      chemotaxonomic and phenotypic analyses showed that strain A4STR04(T) (=LMG 28458
      (T) = CECT 8693(T)) should be classified as representing a novel species of genus
      Fontibacillus, for which the name Fontibacillus solani sp. nov. is proposed.

PMID- 25772304
TI  - A genetic screen in Drosophila implicates Sex comb on midleg (Scm) in tissue
      overgrowth and mechanisms of Scm degradation by Wds.
AB  - The sex comb on midleg (scm) gene encodes a transcriptional repressor and belongs
      to the Polycomb group (PcG) of genes, which regulates growth in Drosophila. Scm
      interacts with Polyhomeotic (a PcG protein) in vitro by recognizing its SPM
      domain. The homologous human protein, Sex comb on midleg-like 2 (Scml2), has been
      implicated in malignant brain tumors. Will die slowly (Wds) is another factor
      that regulates Drosophila development, and its homologous human protein, WD
      repeat domain 5(Wdr5), is part of the mixed lineage leukemia 1(MLL1) complex that
      promotes histone H3Lys4 methylation. Like Scml2, Wdr5 has been implicated in
      certain cancers; this protein plays an important role in leukemogenesis. In this
      study, we find that loss-of-function mutations in Scm result in non-autonomous
      tissue overgrowth in Drosophila, and determine that Scm is essential for
      ommatidium development and important for cell survival in Drosophila.
      Furthermore, our research suggests a relationship between Wds and Scm; Wds
      promotes Scm degradation through ubiquitination in vitro in Drosophila. 

PMID- 25772305
TI  - Parallelized small-scale production of uniformly (13)C-labeled cell extract for
      quantitative metabolome analysis.
AB  - The need for quantitative intracellular metabolome information is central to
      modern applied biotechnology and systems biology. In most cases, sample
      preparation and metabolite analysis result in degradation of metabolites and
      signal suppression due to metabolite instability and matrix effects during LC-MS
      analysis. Therefore the application of uniformly (U) (13)C-labeled cell extract
      as an internal standard has gained interest in recent years. In this study a
      multiple-step protocol has been developed for efficient preparation of U-(13)C
      labeled Escherichia coli cell extracts in stirred-tank bioreactors on a
      milliliter scale with a minimal supply of costly (13)C-labeled substrate.
      Significant reduction of fermentation medium salt concentration in the U-(13)C
      labeled cell extract was achieved to reduce ion-suppression effects during mass
      spectrometric analysis. Additionally, variation of reaction conditions in
      parallel-operated stirred-tank bioreactors on a milliliter scale enables the
      simultaneous preparation of U-(13)C-labeled cell extracts with varying metabolite
      concentrations, which is shown by an example of the labeled phosphoenolpyruvate
      level in E. coli. 

PMID- 25772306
TI  - Quantification of pyrophosphate as a universal approach to determine polymerase
      activity and assay polymerase inhibitors.
AB  - The importance of DNA polymerases in biology and biotechnology, and their
      recognition as potential therapeutic targets, drives development of methods for
      deriving kinetic characteristics of polymerases and their propensity to perform
      polynucleotide synthesis over modified DNA templates. Among various polymerases,
      translesion synthesis (TLS) polymerases enable cells to avoid the cytotoxic
      stalling of replicative DNA polymerases at chemotherapy-induced DNA lesions,
      thereby leading to drug resistance. Identification of TLS inhibitors to overcome
      drug-resistance necessitates the development of appropriate high-throughput
      assays. Since polymerase-mediated DNA synthesis involves the release of inorganic
      pyrophosphate (PPi), we established a universal and fast method for monitoring
      the progress of DNA polymerases based on the quantification of PPi with a
      fluorescence-based assay that we coupled to in vitro primer extension reactions.
      The established assay has a nanomolar detection limit in PPi and enables the
      evaluation of single nucleotide incorporation and DNA synthesis progression
      kinetics. The results demonstrated that the developed assay is a reliable method
      for monitoring TLS and identifying nucleoside and nucleotide-based TLS
      inhibitors.

PMID- 25772307
TI  - Female sex hormone receptors in gallbladder cancer.
AB  - BACKGROUND: Higher incidence of gallbladder cancer among women suggests a role of
      female sex hormones in its etiopathogenesis. OBJECTIVES: This paper aims to study
      the estrogen/progesterone receptor (ER/PR) expression in gallbladder cancer and
      to correlate the receptor expression with the clinicopathological profile of
      patients to understand its implication. MATERIALS AND METHODS: Forty-seven
      patients of gallbladder cancer were studied. Tumor specimens were subjected to
      histopathologic examination. ER/PR expression was evaluated using
      immunohistochemistry (IHC). Receptor expression was correlated with the
      clinicopathological profile of the patients. RESULTS: Of the 47 patients, 11
      (23.4 %) patients expressed sex hormone receptors. Of the receptor-positive
      patients, ER and PR were expressed simultaneously in eight patients while ER and
      PR were expressed individually in two and one patients, respectively. Metaplasia
      (p < 0.009) and dysplasia (p < 0.002) were found significantly more in hormone
      positive group. The presence of hormone receptor correlated with early/operable
      stage of the tumor (p < 0.048). Hormone negativity correlated with
      inoperable/metastatic stage IVB (p < 0.004). The receptor status did not have any
      correlation with age, sex, menopausal status, presence/absence of gallstones,
      tumor type, tumor differentiation, desmoplasia, or necrosis. CONCLUSIONS: ER and
      PR are expressed, mostly simultaneously, in a significant proportion (23.4 %) of
      patients with gallbladder cancer. Receptor expression correlates with metaplasia,
      dysplasia, and early/operable stage of tumor, while its non-expression with
      inoperable/metastatic stage. Receptor study in patients of gallbladder cancer may
      have prognostic implications.

PMID- 25772308
TI  - Long-term lung transplantation in nonhuman primates.
AB  - Despite advances in surgical technique and clinical care, lung transplantation
      still remains a short-term solution for the treatment of end-stage lung disease.
      To date, there has been limited experience in experimental lung transplantation
      using nonhuman primate models. Therefore, we have endeavored to develop a long
      term, nonhuman primate model of orthotopic lung transplantation for the ultimate
      purpose of designing protocols to induce tolerance of lung grafts. Here, we
      report our initial results in developing this model and our observation that the
      nonhuman primate lung is particularly prone to rejection. This propensity toward
      rejection may be a consequence of 1) upregulated nonspecific inflammation, and 2)
      a larger number of pre-existing alloreactive memory T cells, leading to augmented
      deleterious immune responses. Our data show that triple-drug immunosuppression
      mimicking clinical practice is not sufficient to prevent acute rejection in
      nonhuman primate lung transplantation. The addition of horse-derived anti
      thymocyte globulin and a monoclonal antibody to the IL-6 receptor allowed six out
      of six lung recipients to be free of rejection for over 120 days. 

PMID- 25772310
TI  - Geoepidemiological hints about Streptococcus pyogenes strains in relationship
      with acute rheumatic fever.
AB  - Group A Streptococcus (GAS) strains are lately classified on the basis of
      sequence variations in the emm gene encoding the M protein, but despite the high
      number of distinct emm genotypes, the spectrum of phenotypes varying from
      invasive suppurative to non-suppurative GAS-related disorders has still to be
      defined. The relationship of GAS types with the uprising of acute rheumatic fever
      (ARF), a multisystemic disease caused by misdirected anti-GAS response in
      predisposed people, is also obscure. Studies published over the last 15 years
      were retrieved from PubMed using the keywords: "Streptococcus pyogenes" or "group
      A Streptococcus" and "acute rheumatic fever": the prevalence of peculiar emm
      types across different countries of the world is highly variable, depending on
      research designs, year of observation, country involved, patients' age, and
      gender. Most studies revealed that a relatively small number of specific emm/M
      protein types can be considered "rheumatogenic", as potentially characterized by
      the possibility of inducing ARF, with remarkable differences between developing
      and developed countries. The association between emm types and post-streptococcal
      manifestations is challenging, however surveillance of disease-causing variants
      in a specific community with high rate of ARF should be reinforced with the final
      goal of developing a potential primary prophylaxis against GAS infections.

PMID- 25772311
TI  - Prevention and management of lymphedema after breast cancer treatment.
AB  - Lymphedema of the arm after breast cancer treatment continues to challenge
      clinicians worldwide. In this review, we examine the main modalities, both
      nonsurgical and surgical, to prevent and treat this as yet incurable condition. 

PMID- 25772312
TI  - Preterm birth and the school years.

PMID- 25772313
TI  - Conformational properties of cis- and trans-N-Cyclopropylformamide studied by
      microwave spectroscopy and quantum chemical calculations.
AB  - The microwave spectra of cis- and trans-N-cyclopropylformamide, C3H5NHC(?O)H,
      have been investigated in the 31-123 GHz spectral region at room temperature.
      Rotational isomerism about the Cring-N bond is possible for both cis and trans.
      MP2/cc-pVTZ and CCSD/cc-pVTZ calculations indicate that there are two conformers
      in the case of cis, called Cis I and Cis II, while only one rotamer, denoted
      Trans, exists for trans-N-cyclopropylformamide. The quantum chemical methods
      predict that Cis I has an electronic energy that is 8-9 kJ/mol higher than the
      energy of Cis II. The CCSD H-Cring-N-H dihedral angle is 0.0 degrees  in Cis I,
      93.0 degrees  in Cis II and 79.9 degrees  in Trans. The CCSD and MP2 calculations
      predict a slightly nonplanar structure for the amide moiety in both Trans and Cis
      II, whereas Cis I is computed to have a planar amide group bisecting the
      cyclopropyl ring. Surprisingly, the MP2 and CCSD methods predict practically the
      same energy for Trans and Cis II. The spectra of Cis II in the ground state and
      in two vibrationally excited states were assigned, while the spectrum of Cis I
      was not found presumably because of a low Boltzmann population due to a
      relatively large energy difference (8-9 kJ/mol). The spectra of the ground
      vibrational state and seven vibrationally excited states of Trans, were assigned.
      Vibrational frequencies of several of the excited state of both Cis II and Trans
      were determined by relative intensity measurements. The experimental and CCSD
      rotational constants are in satisfactory agreement. The MP2 values of the quartic
      centrifugal distortion constants of both species are in relatively poor agreement
      with their experimental counterparts. The MP2 vibration-rotation constants and
      sextic centrifugal distortion constants have little resemblance with the
      corresponding experimental values. 

PMID- 25772314
TI  - Structural heterogenity of intraluminal content of the prostate: a histochemical
      and ultrastructural study.
AB  - Intraluminal contents of benign and malignant prostatic tissue are associated
      with varying forms of acellular structures. These include corpora amylacea,
      prostatic calculi, and prostatic crystalloids. There are relatively few
      microscopy studies about the characterization of intraluminal structures from
      benign and malignant prostatic glands and little is known about their chemical
      composition. In the present study, we used a combination of special histochemical
      methods, immunohistochemistry, and transmission electron microscopy to
      characterize intraluminal contents of benign and malignant prostate glands. The
      study was done on 33 radical prostatectomy and four transurethral resections of
      prostate specimens. Histochemical methods such as von Kossa, autometallography
      (AMG), as well as PSA immunohistochemistry and transmission electron microscopy
      were performed to characterize intraluminal contents of benign and malignant
      prostate glands. Von Kossa staining was observed in acellular structures, corpora
      amylacea, prostatic calculi, and calcified blood vessels. AMG staining was
      observed in the lumen of small glands, in the epithelium lining prostate glands,
      and corpora amylacea. PSA staining showed prostatic glands with both positive and
      negative corpora amylacea and epithelial cells. Ultrastructural observation
      revealed the presence of a variety of highly heterogeneous aggregates composed of
      fibrillar elements that were similar to those of amyloid. 

PMID- 25772315
TI  - The impact of sleep on female sexual response and behavior: a pilot study.
AB  - INTRODUCTION: The etiological role of sleep disturbance in sexual difficulties
      has been largely overlooked. Research suggests that short sleep duration and poor
      sleep quality lead to poor female sexual response. However, prior research
      consists of cross-sectional studies, and the influence of sleep on sexual
      functioning and behavior has not been prospectively examined. AIM: We sought to
      examine the influence of nightly sleep duration, sleep quality, and sleep onset
      latency on daily female sexual response and activity. METHODS: This study used a
      longitudinal design to study 171 women free of antidepressants and with reliable
      Internet access who were recruited from a university setting in the United
      States. Participants first completed baseline measures in a laboratory, and then
      completed web-delivered surveys at their habitual wake time for 14 consecutive
      days. MAIN OUTCOME MEASURES: All outcome measures were modified for daily recall.
      Participants completed the Profile of Female Sexual Function's desire, subjective
      arousal, and orgasmic functioning scales and the Female Sexual Function Index's
      genital arousal scale, and indicated whether they engaged in partnered sexual
      activity or self-stimulation in response to dichotomous items. RESULTS: Analyses
      revealed that longer sleep duration was related to greater next-day sexual desire
      (b = 0.32, P = 0.02), and that a 1-hour increase in sleep length corresponded to
      a 14% increase in odds of engaging in partnered sexual activity (odds ratio =
      1.14, P < 0.05). In contrast, sleeping longer predicted poorer next-day genital
      arousal (b = -0.19, P < 0.01). However, results showed that women with longer
      average sleep duration reported better genital arousal than women with shorter
      average sleep length (b = 0.54, P = 0.03). CONCLUSIONS: Obtaining sufficient
      sleep is important to the promotion of healthy sexual desire and genital
      response, as well as the likelihood of engaging in partnered sexual activity.
      These relationships were independent of daytime affect and fatigue. Future
      directions may investigate sleep disorders as risk factors for sexual
      dysfunction.

PMID- 25772316
TI  - Targeting GLI proteins in human cancer by small molecules (WO2014116651 A1): a
      patent evaluation.
AB  - The invention reviewed in this patent evaluation is the synthesis and application
      of small molecule inhibitors of Gli transcriptional activity as potential
      anticancer agents. The oncogenic nature of Gli proteins has been traditionally
      associated with the hedgehog (Hh) signaling pathway; however, the recent
      identification of aberrant Gli activation unrelated to Hh signaling has prompted
      drug discovery efforts directly targeting Gli proteins. The central core of the
      compounds described in this patent (WO2014116651 A1) is structurally analogous to
      the pyrazoline scaffold previously disclosed by these inventors. Data describing
      the inhibitory activity of these compounds against the Hh pathway in vitro and in
      Hh-dependent in vivo models of human cancer are not provided. For this patent
      disclosure, the inventors primarily focus on the anticancer properties of their
      compounds in lung and lung-related malignancies. The compounds are moderately
      active in these models, but they do not exhibit the overall preclinical profile
      generally required for advancement into clinical trials. 

PMID- 25772317
TI  - Superiority of pictorial versus verbal presentation and initial exposure in the
      P300-based, complex trial protocol for concealed memory detection.
AB  - Two mock guilty groups had either pictorial or verbal initial exposure to crime
      items (probes) on which they were told they would later be tested. Then each
      subject was tested in two sessions on two successive days with both verbal and
      pictorial presentation, one test modality per session/day. The three dependent
      variables analyzed were three different estimates of the same basic measurement:
      the difference between P300s evoked by key (probe) and irrelevant stimuli. All
      three indexes were significantly increased more by both initial pictorial
      exposure, as well as by pictorial presentation modality, than by verbal exposure
      and presentation. We saw no main effect of exposure-presentation modality
      congruence, as congruence interacted with exposure: The largest probe-irrelevant
      differences were evoked by congruent pictorial exposure and presentation
      modality, and the smallest by congruent verbal exposure and presentation
      modality. 

PMID- 25772318
TI  - Relationship Between Serum Concentrations of Nitisinone and Its Effect on
      Homogentisic Acid and Tyrosine in Patients with Alkaptonuria.
AB  - BACKGROUND: Alkaptonuria (AKU) is a serious genetic disease due to a defect in
      tyrosine metabolism, leading to increased serum levels of homogentisic acid
      (HGA). Nitisinone decreases HGA in AKU, but the concentration-response
      relationship has not been previously reported. OBJECTIVES: To determine the
      relationship between serum concentrations of nitisinone and the effect on both
      HGA and tyrosine; secondly to determine steady-state pharmacokinetics of
      nitisinone in AKU patients. METHOD: Thirty-two patients with AKU received either
      1, 2, 4, or 8 mg nitisinone daily. Urine and serum HGA and serum tyrosine and
      nitisinone were measured during 24 h at baseline (before first dose) and after 4
      weeks of treatment. RESULTS: Nitisinone pharmacokinetics (area under the curve
      [AUC] and maximum concentrations [C max]) were dose proportional. The median oral
      clearance determined in all patients, irrespective of dose, was 3.18 mL/h.kg
      (range 1.6-6.7).Nitisinone decreased urinary excretion of HGA in a concentration
      dependent manner, with a maximum effect seen at average nitisinone concentrations
      of 3 MUmol/L. The association between nitisinone and tyrosine concentrations was
      less pronounced. Serum levels of HGA at Week 4 were below the limit of
      quantitation in 65% of samples, which prevented determination of the relationship
      with nitisinone concentrations. CONCLUSION: Nitisinone exhibits dose-proportional
      pharmacokinetics in the studied dosage interval. Urinary excretion of HGA
      decreases in a concentration-dependent manner, while the increase in tyrosine is
      less clearly related to nitisinone concentrations.

PMID- 25772319
TI  - Mitochondrial Complex III Deficiency Caused by TTC19 Defects: Report of a Novel
      Mutation and Review of Literature.
AB  - We report about a patient with infantile-onset neurodegenerative disease
      associated with isolated mitochondrial respiratory chain complex III (cIII)
      deficiency. The boy, now 13 years old, presented with language regression and
      ataxia at 4 years of age and then showed a progressive course resulting in the
      loss of autonomous gait and speaking during the following 2 years. Brain MRI
      disclosed bilateral striatal necrosis. Sequencing of a panel containing nuclear
      genes associated with cIII deficiency revealed a previously undescribed
      homozygous rearrangement (c.782_786delinsGAAAAG) in TTC19 gene, which results in
      a frameshift with premature termination (p.Glu261Glyfs(*)8). TTC19 protein was
      absent in patient's fibroblasts. TTC19 encodes tetratricopeptide 19, a putative
      assembly factor for cIII. To date TTC19 mutations have been reported only in few
      cases, invariably associated with cIII deficiency, but presenting heterogeneous
      clinical phenotypes. We reviewed the genetic, biochemical, clinical and
      neuroradiological features of TTC19 mutant patients described to date. 

PMID- 25772320
TI  - Niemann-Pick Type C-2 Disease: Identification by Analysis of Plasma Cholestane
      3beta,5alpha,6beta-Triol and Further Insight into the Clinical Phenotype.
AB  - INTRODUCTION: Niemann-Pick type C disease is a rare disorder caused by impaired
      intracellular lipid transport due to mutations in either the NPC1 or the NPC2
      gene. Ninety-five % of NPC patients show mutations in the NPC1 gene. A much
      smaller number of patients suffer from NPC2 disease and present respiratory
      failure as one of the most frequent symptoms. Several plasma oxysterols are
      highly elevated in NPC1 and can be used as a biomarker in the diagnosis of NPC1.
      METHODS: Plasma cholestane-3beta,5alpha,6beta-triol was evaluated as biomarker
      for NPC2 by GC/MS and LC-MS/MS analysis. The diagnosis was confirmed by Sanger
      sequencing and filipin staining. RESULTS: We report three NPC2 patients with
      typical respiratory problems and a detailed description of the nature of the lung
      disease in one of them. All patients had elevated levels of plasma cholestane
      3beta,5alpha,6beta-triol. In two of these patients, the positive oxysterol result
      led to a rapid diagnosis of NPC2 by genetic analysis. The phenotype of the third
      patient has been described previously. In this patient a cholestane
      3beta,5alpha,6beta-triol concentration markedly above the reference range was
      found. CONCLUSIONS: Measurement of plasma cholestane-3beta,5alpha,6beta-triol
      enables to discriminate between controls and NPC1 and NPC2 patients, making it a
      valuable biomarker for the rapid diagnosis not only for NPC1 but also for NPC2
      disease.The measurement of oxysterols should be well kept in mind in the
      differential diagnosis of lysosomal diseases, as the elevation of oxysterols in
      plasma may speed up the diagnosis of NPC1 and NPC2.

PMID- 25772321
TI  - The Modulatory Effects of the Polymorphisms in GLA 5'-Untranslated Region Upon
      Gene Expression Are Cell-Type Specific.
AB  - Lysosomal alpha-galactosidase A (alphaGal) is the enzyme deficient in Fabry
      disease (FD). The 5'-untranslated region (5'UTR) of the alphaGal gene (GLA) shows
      a remarkable degree of variation with three common single nucleotide
      polymorphisms at nucleotide positions c.-30G>A, c.-12G>A and c.-10C>T. We have
      recently identified in young Portuguese stroke patients a fourth polymorphism, at
      c.-44C>T, co-segregating in cis with the c.-12A allele. In vivo, the c.-30A
      allele is associated with higher enzyme activity in plasma, whereas c.-10T is
      associated with moderately decreased enzyme activity in leucocytes. Limited data
      suggest that c.-44T might be associated with increased plasma alphaGal activity.
      We have used a luciferase reporter system to experimentally assess the relative
      modulatory effects on gene expression of the different GLA 5'UTR polymorphisms,
      as compared to the wild-type sequence, in four different human cell lines. Group
      wise, the relative luciferase expression patterns of the various GLA variant
      isoforms differed significantly in all four cell lines, as evaluated by non
      parametric statistics, and were cell-type specific. Some of the post hoc pairwise
      statistical comparisons were also significant, but the observed effects of the
      GLA 5'UTR polymorphisms upon the luciferase transcriptional activity in vitro did
      not consistently replicate the in vivo observations.These data suggest that the
      GLA 5'UTR polymorphisms are possible modulators of the alphaGal expression.
      Further studies are needed to elucidate the biological and clinical implications
      of these observations, particularly to clarify the effect of these polymorphisms
      in individuals carrying GLA variants associated with high residual enzyme
      activity, with no or mild FD clinical phenotypes. 

PMID- 25772322
TI  - Cobalamin C Disease Missed by Newborn Screening in a Patient with Low Carnitine
      Level.
AB  - Cobalamin C (CblC) disease is the most common inherited disorder of intracellular
      cobalamin metabolism. It is a multisystemic disorder mainly affecting the eye and
      brain and characterized biochemically by methylmalonic aciduria, low methionine
      level, and homocystinuria. We report a patient found to have CblC disease who
      initially presented with low carnitine and normal propionylcarnitine (C3) levels
      on newborn screen. Newborn screening likely failed to detect CblC in this patient
      because of both his low carnitine level and the presence of a mild phenotype. 

PMID- 25772323
TI  - Freezing of gait and affective theory of mind in Parkinson disease.
AB  - BACKGROUND: Affective "Theory of Mind" (ToM) is the specific ability to represent
      own and others' emotional states and feelings. Several studies examined affective
      ToM ability in patients with Parkinson's disease (PD), using the "Reading the
      Mind in the Eyes test" (RMET). However, there has been no agreement as to whether
      or not affective ToM ability is impaired in PD and such discrepancy may be due to
      the heterogeneous clinical presentation of PD. Affective disturbance has been
      linked to the akinetic-rigid form of PD and to gait disturbances, like freezing
      of gait (FOG). Particularly, FOG has been associated with dysfunction in striatum
      ability of processing affective inputs. Here we hypothesized that the presence of
      FOG can be associated with impaired affective ToM ability in PD patients.
      METHODS: We evaluated ToM by means of RMET and executive functions using the
      Tower Of London (ToL) test in 29 PD patients (15 with FOG and 14 without FOG) and
      19 healthy age-matched subjects. RESULTS: Our results showed that affective ToM
      is abnormal in PD patients, compared to healthy subjects and that it is more
      impaired in patients with FOG than in patients without FOG. Further, PD patients
      with FOG performed worse than PD patients without FOG on the ToL test.
      CONCLUSION: The affective aspects of ToM can be associated to FOG in patients
      with PD, thus supporting the idea that FOG is caused by a complex interplay
      between motor, cognitive and affective factors, rather than being a pure motor
      problem.

PMID- 25772324
TI  - Symptom severity in patients with functional motor symptoms: Patient's perception
      and doctor's clinical assessment.
AB  - BACKGROUND: Beliefs and expectations about symptoms and an abnormal direction of
      attention towards the body have been proposed as important mechanistic factors in
      the pathophysiology of functional motor symptoms (FMS). We therefore aimed to
      evaluate patients' awareness/perception of the presence and severity of their own
      symptoms before and while watching themselves in a video and to compare this with
      doctors' assessment of the presence and severity of FMS, based on video
      evaluation. METHODS: We evaluated 16 patients affected by FMS. Patients were
      invited to give a "subjective evaluation" of their symptoms. Afterwards, patients
      were invited to watch a video of themselves and to judge the presence of symptoms
      in the different body parts and, if so, to rate the severity. Patients' videos
      were also assessed by a rater with expertise in FMS. RESULTS: Patients judged
      their symptoms to be more severe on subjective evaluation than when viewing a
      video of themselves (p = 0.002; t = 3.656). Subjective evaluation of symptom
      severity by patients was higher than that of raters viewing a video of the
      patient (p < 0.001, t = 4.860), but there was only a trend towards a difference
      between video ratings of severity by patients and independent raters (p = 0.017,
      t = 2.962 with p set at 0.016 according to Bonferroni correction). CONCLUSIONS:
      Our study shows that patients with FMS tend to overestimate the severity of their
      symptoms compared independent rating. However, when viewing a video of themselves
      they rated their symptoms as less severe and closer to those of independent
      raters.

PMID- 25772325
TI  - Prognosis of women with early breast cancer and PIK3CA mutations.

PMID- 25772327
TI  - Nanotubular structured Si-based multicomponent anodes for high-performance
      lithium-ion batteries with controllable pore size via coaxial electro-spinning.
AB  - We demonstrate a simple but straightforward process for the synthesis of nanotube
      type Si-based multicomponents by combining a coaxial electrospinning technique
      and subsequent metallothermic reduction reaction. Si-based multicomponent anodes
      consisting of Si, alumina and titanium silicide show several advantages for high
      performance lithium-ion batteries. Alumina and titanium silicide, which have high
      mechanical properties, act as an effective buffer layer for the large volume
      change of Si, resulting in outstanding volume suppression behavior (volume
      expansion of only 14%). Moreover, electrically conductive titanium silicide
      layers located at the inner and outer layers of a Si nanotube exhibit a high
      initial coulombic efficiency of 88.5% and an extraordinary rate capability.
      Nanotubular structured Si-based multicomponents with mechanically and
      electrically improved components can be used as a promising alternative to
      conventional graphite anode materials. This synthetic route can be extended to
      other high capacity lithium-ion battery anode materials. 

PMID- 25772328
TI  - [Antibiotic ointments and methicillin-resistant Staphylococcus aureus with a
      reservoir in a healthcare worker in a tertiary hospital].

PMID- 25772326
TI  - Antiangiogenic therapy in recurrent breast cancer with lymphangitic spread to the
      chest wall: A randomized phase II trial of bevacizumab with sequential or
      concurrent oral vinorelbine and capecitabine.
AB  - OBJECTIVES: To assess efficacy of bevacizumab in combination with oral
      chemotherapy in patients with breast cancer with lymphangitic spread to the chest
      wall (LBC). To identify surrogate biomarkers of response to bevacizumab. PATIENTS
      AND METHODS: We randomly assigned patients to receive bevacizumab plus either
      sequential or concurrent oral vinorelbine and capecitabine every 3 weeks. The
      primary endpoint was time to ultimate progression (TTP); the response rate and
      overall survival (OS) were secondary endpoints. We performed gene expression
      profiling on baseline tissue samples collected from triple negative LBC. We
      assessed circulating endothelial cells (CEC), circulating endothelial progenitors
      (CEP) and circulating pericyte progenitors (CPP). RESULTS: A total of 66 patients
      were enrolled. There was no difference in TTP (median TTP 5.3 vs. 4.8 months, p =
      0.21) and in OS (median OS 15.8 vs 11.9 months; p = 0.25) when comparing
      concurrent vs sequential treatment, respectively. Response rate was 25% vs 28% in
      the concurrent vs sequential arm (p = 1.00), respectively. A set of 16 genes
      predictive of response to bevacizumab was identified. The counts of CEPs and
      viable CECs below the median value were associated with an improved overall
      survival: 26.6 vs 9.5 months for CEPs and 22.6 vs 11.0 months for viable CECs,
      respectively (p = 0.02). CONCLUSIONS: Oral chemotherapy and bevacizumab (BEVIX)
      is an active regimen in patients with LBC. We support the importance of using LBC
      as a biological model for investigating angiogenesis inhibitors. CECs and CEPs
      biomarkers have been identified as predictive markers of outcome and warrant
      further investigation.

PMID- 25772329
TI  - Comparison of clinical categories for Escherichia coli harboring specific qnr and
      chromosomal-mediated fluoroquinolone resistance determinants according to CLSI
      and EUCAST.
AB  - EUCAST breakpoints are more restrictive than those defined by CLSI. This study
      highlights the discrepancies between CLSI and EUCAST in a well characterized
      isogenic Escherichia coli collection and their correlations with specific
      quinolone resistance mechanisms. The greatest number of discrepancies was
      observed in strains containing 2-4 resistance mechanisms (MIC values on the
      borderline of clinical resistance). Bearing in mind that quinolones are
      concentration dependent antimicrobial agents, small changes in MIC may have
      relevant consequences for treatment outcomes. 

PMID- 25772309
TI  - The Fibroblast Growth Factor signaling pathway.
AB  - The signaling component of the mammalian Fibroblast Growth Factor (FGF) family is
      comprised of eighteen secreted proteins that interact with four signaling
      tyrosine kinase FGF receptors (FGFRs). Interaction of FGF ligands with their
      signaling receptors is regulated by protein or proteoglycan cofactors and by
      extracellular binding proteins. Activated FGFRs phosphorylate specific tyrosine
      residues that mediate interaction with cytosolic adaptor proteins and the RAS
      MAPK, PI3K-AKT, PLCgamma, and STAT intracellular signaling pathways. Four
      structurally related intracellular non-signaling FGFs interact with and regulate
      the family of voltage gated sodium channels. Members of the FGF family function
      in the earliest stages of embryonic development and during organogenesis to
      maintain progenitor cells and mediate their growth, differentiation, survival,
      and patterning. FGFs also have roles in adult tissues where they mediate
      metabolic functions, tissue repair, and regeneration, often by reactivating
      developmental signaling pathways. Consistent with the presence of FGFs in almost
      all tissues and organs, aberrant activity of the pathway is associated with
      developmental defects that disrupt organogenesis, impair the response to injury,
      and result in metabolic disorders, and cancer. For further resources related to
      this article, please visit the WIREs website.

PMID- 25772330
TI  - Mucoadhesive polyacrylamide nanogel as a potential hydrophobic drug carrier for
      intravesical bladder cancer therapy.
AB  - In this paper, amine-functionalized polyacrylamide nanogels (PAm-NH2) loaded with
      docetaxel (DTX) were evaluated as a mucoadhesive and sustained intravesical drug
      delivery (IDD) system for potential bladder cancer therapy. Nanogels have not
      been applied for such therapy before. The mucoadhesiveness of the PAm-NH2
      nanogels, which is a critical factor for IDD application, was investigated using
      the mucin-particle method and by analyzing the direct attachment of the PAm-NH2
      nanogels onto the luminal surface of porcine urinary bladder. DTX, as a model
      hydrophobic drug, was successfully loaded into hydrophilic PAm-NH2 nanogels with
      high loading efficiency (>90%), and sustained release of DTX from the nanogels
      over 9 days in artificial urine was achieved. The nanogels were also taken in by
      bladder cancer cells in a concentration-dependent manner. The efficiency of the
      DTX-loaded nanogels in killing UMUC3 and T24 bladder cancer cells was determined
      to be equivalent to free DTX, and the morphology of the bladder urothelium was
      not adversely altered by the PAm-NH2 nanogels. These findings indicate that such
      mucoadhesive nanogels are potentially a promising candidate for intravesical
      delivery of hydrophobic drugs in bladder cancer therapy.

PMID- 25772331
TI  - Distal airways are protected from goblet cell metaplasia by diminished expression
      of IL-13 signalling components.
AB  - BACKGROUND: Increased mucus production is a critical factor impairing lung
      function in patients suffering from bronchial asthma, the most common chronic
      inflammatory lung disease worldwide. OBJECTIVE: This study aimed at investigating
      whether goblet cell (GC) metaplasia and mucus production are differentially
      regulated in proximal and distal airways. METHODS: Female Balb/c mice were
      sensitized to ovalbumin (OVA) and challenged with an OVA-aerosol on two
      consecutive days for 1 week (acute) or 12 weeks (chronic). Real-time RT-PCR
      analysis was applied on microdissected airways. RESULTS: In acutely and
      chronically OVA-challenged mice, GC metaplasia and mucus production were observed
      in proximal but not in distal airways. In contrast, inflammation reflected by the
      infiltration of eosinophils and expression of the TH2-type cytokines IL-4 and IL
      13 was increased in both proximal and distal airways. Abundance of IL-13Ralpha1
      was lower in distal airways of healthy control mice. Under acute and chronic OVA
      exposure, activation of IL-13Ralpha1-dependent signalling cascade, reflected by
      Spdef and Foxo3A transcription factors, was attenuated in distal compared to
      proximal airways. CONCLUSION AND CLINICAL RELEVANCE: These data indicate that
      distal airways might be less sensitive to IL-13-induced GC metaplasia and mucus
      production through lower expression of IL-13Ralpha1 and attenuated activation of
      downstream signalling. This might represent a protective strategy to prevent
      mucus plugging of distal airways and thus impaired ventilation of attached
      alveoli.

PMID- 25772332
TI  - Direct observation of the dealloying process of a platinum-yttrium nanoparticle
      fuel cell cathode and its oxygenated species during the oxygen reduction
      reaction.
AB  - Size-selected 9 nm PtxY nanoparticles have recently shown an outstanding
      catalytic activity for the oxygen reduction reaction, representing a promising
      cathode catalyst for proton exchange membrane fuel cells (PEMFCs). Studying their
      electrochemical dealloying is a fundamental step towards the understanding of
      both their activity and stability. Herein, size-selected 9 nm PtxY nanoparticles
      have been deposited on the cathode side of a PEMFC specifically designed for in
      situ ambient pressure X-ray photoelectron spectroscopy (APXPS). The dealloying
      mechanism was followed in situ for the first time. It proceeds through the
      progressive oxidation of alloyed Y atoms, soon leading to the accumulation of
      Y(3+) cations at the cathode. Acid leaching with sulfuric acid is capable of
      accelerating the dealloying process and removing these Y(3+) cations which might
      cause long term degradation of the membrane. The use of APXPS under near
      operating conditions allowed observing the population of oxygenated surface
      species as a function of the electrochemical potential. Similar to the case of
      pure Pt nanoparticles, non-hydrated hydroxide plays a key role in the ORR
      catalytic process. 

PMID- 25772333
TI  - Lipid droplet dynamics at early stages of Mycobacterium marinum infection in
      Dictyostelium.
AB  - Lipid droplets exist in virtually every cell type, ranging not only from mammals
      to plants, but also to eukaryotic and prokaryotic unicellular organisms such as
      Dictyostelium and bacteria. They serve among other roles as energy reservoir that
      cells consume in times of starvation. Mycobacteria and some other intracellular
      pathogens hijack these organelles as a nutrient source and to build up their own
      lipid inclusions. The mechanisms by which host lipid droplets are captured by the
      pathogenic bacteria are extremely poorly understood. Using the powerful
      Dictyostelium discoideum/Mycobacterium marinum infection model, we observed that,
      immediately after their uptake, lipid droplets translocate to the vicinity of the
      vacuole containing live but not dead mycobacteria. Induction of lipid droplets in
      Dictyostelium prior to infection resulted in a vast accumulation of neutral
      lipids and sterols inside the bacterium-containing compartment. Subsequently,
      under these conditions, mycobacteria accumulated much larger lipid inclusions.
      Strikingly, the Dictyostelium homologue of perilipin and the murine perilipin 2
      surrounded bacteria that had escaped to the cytosol of Dictyostelium or
      microglial BV-2 cells respectively. Moreover, bacterial growth was inhibited in
      Dictyostelium plnA knockout cells. In summary, our results provide evidence that
      mycobacteria actively manipulate the lipid metabolism of the host from very early
      infection stages. 

PMID- 25772334
TI  - Dixon water-fat separation in PROPELLER MRI acquired with two interleaved echoes.
AB  - PURPOSE: To propose a novel combination of robust Dixon fat suppression and
      motion insensitive PROPELLER (periodically rotated overlapping parallel lines
      with enhanced reconstruction) MRI. METHODS: Two different echoes were acquired
      interleaved in each shot enabling water-fat separation on individual blades. Fat,
      which was blurred in standard PROPELLER because the water-fat shift (WFS) rotated
      with the blades, was shifted back in each blade. Additionally, field maps
      obtained from the water-fat separation were used to unwarp off-resonance-induced
      shifts in each blade. PROPELLER was then applied to the water, corrected fat, or
      recombined water-fat blades. This approach was compared quantitatively in
      volunteers with regard to motion estimation and signal-to-noise ratio (SNR) to a
      standard PROPELLER acquisition with minimal WFS and fat suppression. RESULTS:
      Shifting the fat back in each blade reduced errors in the translation correction.
      SNR in the proposed Dixon PROPELLER was 21% higher compared with standard
      PROPELLER with identical scan time. High image quality was achieved even when the
      volunteers were moving during data acquisition. Furthermore, sharp water-fat
      borders and image details were seen in areas where standard PROPELLER suffered
      from blurring when acquired with a low readout bandwidth. CONCLUSION: The
      proposed method enables motion-insensitive PROPELLER MRI with robust fat
      suppression and reduced blurring. Additionally, fat images are available if
      desired.

PMID- 25772335
TI  - Efficacy of low concentrations of sodium hypochlorite and low-powered Er,Cr:YSGG
      laser activated irrigation against an Enterococcus faecalis biofilm.
AB  - AIM: To establish the antibacterial efficacy of low concentrations of sodium
      hypochlorite with and without Er,Cr:YSGG laser activation on Enterococcus
      faecalis biofilms in extracted teeth. METHODOLOGY: The root canals of 96
      decoronated single-rooted extracted human teeth were prepared to a size 40, 0.06
      taper 1 mm beyond the apex. They were mounted within a flow cell, which was
      sterilized before pumping a nutrient media through the root canals. The flow cell
      was inoculated with E. faecalis (ATCC 700802) and cultivated for 4 weeks. The
      root-ends were sealed, and the roots were then subjected to one of six treatment
      groups: group 1: syringe irrigation (SI) with saline (control) using a 27 -gauge
      Monoject needle 1 mm from the apex for 2 min; group 2: as for group 1 but with 1%
      NaOCl; group 3: as for group 1 but with 4% NaOCl; group 4: 0.5% NaOCl irrigation
      for 15 s followed by laser-activated irrigation (LAI) with four 15-s cycles
      replenishing the irrigant between cycles; group 5: as for group 4 but with 1%
      NaOCl as the irrigant; group 6: as for group 4 but with 4% NaOCl as the irrigant.
      Following treatment, teeth were crushed and viable bacteria were quantitated by
      serial dilution and plating. The colony-forming unit values were compared between
      groups using one-way anova and Tukey-adjusted post hoc tests. A two-tailed P
      value of <0.05 was considered statistically significant. RESULTS: The mean number
      of cells recovered from the 1% NaOCl SI group was significantly higher than that
      from the 4% NaOCl LAI group (P = 0.02). CONCLUSION: Within the limitations of
      this laboratory study, low-powered (0.5 W) Er,Cr:YSGG laser activation did not
      improve the antibacterial effect of low concentrations of sodium hypochlorite.

PMID- 25772336
TI  - The Monty Hall dilemma with pigeons: No, you choose for me.
AB  - In the Monty Hall dilemma, humans are initially given a choice among three
      alternatives, one of which has a hidden prize. After they have chosen, but before
      revealing whether they have won the prize, subjects are shown that one of the
      remaining alternatives does not have the prize, and they are asked whether they
      want to stay with their original choice or switch to the remaining alternative.
      Switching results in obtaining the prize two thirds of the time, but even after
      considerable training, humans fail to consistently adopt the optimal strategy of
      switching. Pigeons, however, show closer-to-optimal switching performance with
      this task. One of the reasons that humans choose suboptimally is their mistaken
      assumption that with two alternatives, the probabilities of winning the prize are
      the same for staying and switching, and staying may be preferred because of a
      sense of endowment (ownership of the initial response). When we tried to produce
      an endowment effect in pigeons by requiring 20 pecks (rather than one peck) for
      the initial choice, it actually resulted in faster acquisition of the switching
      response. In the present research with pigeons, we examined the finding from
      human research that subjects are more likely to switch if they are not
      responsible for making the initial choice (another approach to the endowment
      effect). Inconsistent with the findings with humans, we found that when the
      initial choice was made for the pigeons, they actually showed less of a tendency
      to switch than did pigeons that made the initial choice themselves. 

PMID- 25772337
TI  - Oxytocin and MDMA ('Ecstasy') enhance social reward in rats.
AB  - RATIONALE: Oxytocin (OT), vasopressin (AVP) and 3,4 methylenedioxymethamphetamine
      (MDMA, 'Ecstasy') all increase social interaction in rats, perhaps by enhancing
      the rewarding value of social encounters. OBJECTIVES: Here, we used the
      conditioned place preference (CPP) paradigm to assess the intrinsic rewarding
      effects of OT, AVP and MDMA, and whether these effects are enhanced by the
      presence of a conspecific, or a dynamic, tactile object (a tennis ball). METHODS:
      Adult male rats received conditioning sessions in a CPP apparatus twice a day
      (vehicle at 10 a.m., drug at 3 p.m.). Experiment 1 involved conditioning with OT
      (0.5 mg/kg, intraperitoneal (i.p.)), AVP (0.005 mg/kg, i.p.) or MDMA (5 mg/kg,
      i.p.). Experiments 2 and 3 involved conditioning with the same treatments but in
      the presence of a conspecific receiving the same treatment (social-CPP) or in the
      presence of a tennis ball (object-CPP), respectively. Conditioned place
      preference was assessed 24 h, 2 weeks and 4 weeks later. RESULTS: OT, AVP and
      MDMA did not produce a conventional CPP. However, when the conditioning
      environment also contained a conspecific both OT and MDMA induced a significant
      CPP lasting for at least 4 weeks. Rats given OT and MDMA also developed a more
      modest yet significant CPP for the environment where they encountered a tennis
      ball. CONCLUSIONS: These results indicate that OT and MDMA can augment the
      rewarding effects of social interaction, but also interaction with a dynamic and
      tactile non-social object. AVP does not condition social- or object-CPPs and may
      promote social proximity by inducing generalized anxiety and defensive
      aggregation.

PMID- 25772338
TI  - Cannabinoid withdrawal in mice: inverse agonist vs neutral antagonist.
AB  - RATIONALE: Previous reports shows rimonabant's inverse properties may be a
      limiting factor for treating cannabinoid dependence. To overcome this limitation,
      neutral antagonists were developed, to address mechanisms by which an inverse
      agonist and neutral antagonist elicit withdrawal. OBJECTIVE: The objective of
      this study is to introduce an animal model to study cannabinoid dependence by
      incorporating traditional methodologies and profiling novel cannabinoid ligands
      with distinct pharmacological properties/modes of action by evaluating their
      pharmacological effects on CB1-receptor (CB1R) related physiological/behavioral
      endpoints. METHODS: The cannabinergic AM2389 was acutely characterized in the
      tetrad (locomotor activity, analgesia, inverted screen/catalepsy bar test, and
      temperature), with some comparisons made to Delta(9)-tetrahydrocannabinol (THC).
      Tolerance was measured in mice repeatedly administered AM2389. Antagonist
      precipitated withdrawal was characterized in cannabinoid-adapted mice induced by
      either centrally acting antagonists, rimonabant and AM4113, or an antagonist with
      limited brain penetration, AM6545. RESULTS: In the tetrad, AM2389 was more potent
      and longer acting than THC, suggesting a novel approach for inducing dependence.
      Repeated administration of AM2389 led to tolerance by attenuating hypothermia
      that was induced by acute AM2389 administration. Antagonist-precipitated
      withdrawal signs were induced by rimonabant or AM4113, but not by AM6545.
      Antagonist-precipitated withdrawal was reversed by reinstating AM2389 or THC.
      CONCLUSIONS: These findings suggest cannabinoid-precipitated withdrawal may not
      be ascribed to the inverse properties of rimonabant, but rather to rapid
      competition with the agonist at the CB1R. This withdrawal syndrome is likely
      centrally mediated, since only the centrally acting CB1R antagonists elicited
      withdrawal, i.e., such responses were absent after the purported peripherally
      selective CB1R antagonist AM6545.

PMID- 25772339
TI  - Basolateral amygdala and ventral hippocampus in stress-induced amplification of
      nicotine self-administration during reacquisition in rat.
AB  - RATIONALE: Cigarette smoking remains the leading cause of preventable morbidity
      and mortality in the USA, although only 3-5 % of quitters are successful for 6-12
      months. Stress during abstinence increases the likelihood of relapse to smoking.
      We recently reported that repeated stress during abstinence from operant nicotine
      self-administration (SA) amplifies the reacquisition of nicotine SA and affects
      the diurnal intake of nicotine in rats. Herein, we sought to identify brain
      regions critical for the expression of stress-enhanced nicotine SA during
      reacquisition. METHODS: Rats acquired nicotine SA (FR5) with virtually unlimited
      drug access (23 h/day). During abstinence (8 day), 30 min of restraint stress was
      applied on days 1, 3, 5, and 7. Beginning day 8, nicotine SA was reacquired over
      5 days, and basolateral amygdala (BLA) was inactivated bilaterally or
      disconnected from nucleus accumbens core (NAcc). Similarly, ventral hippocampus
      (vHP) was inactivated or disconnected from BLA. RESULTS: Bilateral inactivation
      (muscimol + baclofen) of BLA or disconnection from NAcc abolished the stress
      enhanced reacquisition of nicotine SA without affecting basal levels of nicotine
      SA. Similarly, bilateral inactivation of vHP or disconnection of vHP and BLA also
      abolished stress-enhanced reacquisition of nicotine SA. CONCLUSION: BLA, vHP, and
      functional interactions between BLA-NAcc and vHP-BLA are required for expression
      of stress-enhanced nicotine SA during reacquisition. However, without stress,
      these functional interactions are not necessary for reexpression of nicotine SA
      during reacquisition. Therefore, BLA, vHP, and these regional interactions
      specifically mediate the effects of repeated stress on the reacquisition of
      nicotine SA behavior.

PMID- 25772340
TI  - Concurrent coevolution of intra-organismal cheaters and resisters.
AB  - The evolution of multicellularity is a major transition that is not yet fully
      understood. Specifically, we do not know whether there are any mechanisms by
      which multicellularity can be maintained without a single-cell bottleneck or
      other relatedness-enhancing mechanisms. Under low relatedness, cheaters can
      evolve that benefit from the altruistic behaviour of others without themselves
      sacrificing. If these are obligate cheaters, incapable of cooperating, their
      spread can lead to the demise of multicellularity. One possibility, however, is
      that cooperators can evolve resistance to cheaters. We tested this idea in a
      facultatively multicellular social amoeba, Dictyostelium discoideum. This amoeba
      usually exists as a single cell but, when stressed, thousands of cells aggregate
      to form a multicellular organism in which some of the cells sacrifice for the
      good of others. We used lineages that had undergone experimental evolution at
      very low relatedness, during which time obligate cheaters evolved. Unlike earlier
      experiments, which found resistance to cheaters that were prevented from
      evolving, we competed cheaters and noncheaters that evolved together, and
      cheaters with their ancestors. We found that noncheaters can evolve resistance to
      cheating before cheating sweeps through the population and multicellularity is
      lost. Our results provide insight into cheater-resister coevolutionary dynamics,
      in turn providing experimental evidence for the maintenance of at least a simple
      form of multicellularity by means other than high relatedness.

PMID- 25772341
TI  - Mental Health Treatment for Older Veterans Newly Diagnosed with PTSD: A National
      Investigation.
AB  - OBJECTIVE: Older veterans are the largest cohort served by the U.S. Department of
      Veterans Affairs (VA). The aim of this study was to examine mental health service
      utilization among older veterans recently diagnosed with posttraumatic stress
      disorder (PTSD), with an interest in sociodemographic and clinical
      characteristics related to receipt and type of mental health treatment. DESIGN:
      VA National administrative data set and pharmacy records. SETTING: VA Healthcare
      System. PARTICIPANTS: The sample comprised 96,249 veterans aged 50+ years who
      received a new diagnosis of PTSD between fiscal years 2008-2011. MEASUREMENTS:
      Demographic/clinical characteristics and treatment variables (receipt of mental
      health treatment; number of days before first appointment; receipt of
      psychotherapy, medication, or combination treatment; type of medication; number
      of psychotherapy visits) were assessed and relations were examined using
      logistic, negative binomial, and Cox regressions. RESULTS: The majority of older
      veterans with newly diagnosed PTSD received at least one follow-up mental health
      visit. Increasing age was associated with decreased odds of receipt of any type
      of mental health treatment, and psychiatric comorbidities and greater number of
      medical appointments were associated with increased odds of treatment. Among
      veterans who received treatment, increased age was associated with decreased odds
      of receiving both psychotherapy and pharmacotherapy, decreased number of
      psychotherapy visits, and increased waiting times. CONCLUSION: Among older
      veterans recently diagnosed with PTSD in the VA healthcare system, older
      individuals, particularly those over 80 years old, are at risk of not receiving
      timely and appropriate mental health treatment, indicating targeted outreach to
      this population could be helpful in improving care.

PMID- 25772343
TI  - Tumor burden evaluation in NF1 patients with plexiform neurofibromas in daily
      clinical practice.
AB  - BACKGROUND: Existing volumetric measurements of plexiform neurofibromas (PNs) are
      time consuming and error prone, as they require delineation of PN boundaries, a
      procedure that is not practical in the typical clinical setting. The aim of this
      study is to assess the Plexiform Neurofibroma Instant Segmentation Tool (PNist),
      a novel semi-automated segmentation program that we developed for PN delineation
      in a clinical context. PNist was designed to greatly simplify volumetric
      assessment of PNs through use of an intuitive user interface while providing
      objectively consistent results with minimal interobserver and intraobserver
      variabilities in reasonable time. MATERIALS AND METHODS: PNs were measured in 30
      magnetic resonance imaging (MRI) scans from 12 patients with neurofibromatosis 1.
      Volumetric measurements were performed using PNist and compared to a standard
      semi-automated volumetric method (Analyze 9.0). RESULTS: High correlation was
      detected between PNist and the semi-automated method (R(2) = 0.996), with a mean
      volume overlap error of 9.54 % and low intraobserver and interobserver
      variabilities. The segmentation time required for PNist was 60 % of the time
      required for Analyze 9.0 (360 versus 900 s, respectively). PNist was also
      reliable when assessing changes in tumor size over time, compared to the existing
      commercial method. CONCLUSIONS: Our study suggests that the new PNist method is
      accurate, intuitive, and less time consuming for PN segmentation compared to
      existing commercial volumetric methods. The workflow is simple and user-friendly,
      making it an important clinical tool to be used by radiologists, neurologists and
      neurosurgeons on a daily basis, helping them deal with the complex task of
      evaluating PN burden and progression.

PMID- 25772342
TI  - Second primary malignancy risk among patients with gastric cancer: a nationwide
      population-based study in Taiwan.
AB  - BACKGROUND: Several studies have reported an increase in second primary
      malignancies (SPMs) among gastric cancer patients. METHODS: Patients who were
      newly diagnosed with gastric cancer between 1997 and 2011 were recruited from the
      Taiwan National Health Insurance database. Those who had antecedent malignancies
      or gastrointestinal stromal tumor were excluded. Standardized incidence ratios
      (SIRs) of SPMs were calculated. Risk factors for cancer development were analyzed
      by Cox proportional hazards models. Effects of treatments for gastric cancer were
      treated as time-dependent variables. RESULTS: During the 15-year study period,
      47,729 gastric cancer patients were recruited. Overall, 2,110 SPMs developed
      during a total follow-up of 137,798 person-years. The SIR for all cancers was
      1.46. The SIRs for specific follow-up periods were 1.43, 1.41, and 1.21 at >10
      years, 5-10 years, and 1-5 years, respectively. After excluding SPMs that
      developed within 1 year, significantly higher SIRs were seen for cancers of the
      head and neck (1.34), esophagus (2.16), colon and rectum (1.37), bones and soft
      tissues (1.95), ovaries (2.89), bladder (1.47), or kidneys (1.44), as well as non
      Hodgkin's lymphoma (5.56). Multivariate analysis showed that age >=70 years
      [hazard ratio (HR) 1.19], being male (HR 1.37), diabetes mellitus (HR 1.30),
      chronic obstructive pulmonary disease (HR 1.17), and liver cirrhosis (HR 1.94)
      were independent risk factors. Radiotherapy (HR 1.24) and chemotherapy (HR 1.87)
      were independent risk factors, but surgery (HR 0.67) was not. CONCLUSIONS:
      Patients with gastric cancer are at increased risk of developing SPM. Close
      surveillance of patients with risk factors over a longer period should be
      considered.

PMID- 25772344
TI  - Anatomy of lumbosacral spinal nerve roots.

PMID- 25772345
TI  - Common features of the cerebral perforating arteries and their clinical
      significance.
AB  - BACKGROUND: The perforating vessels supply very important regions of the brain
      stem and diencephalon, as well as the basal ganglia and internal capsule. Some of
      their micro-anatomical characteristics are still not well known. The aim of this
      study was to examine and evaluate the features of all the perforating vessels.
      METHODS: The arteries of 24-32 cerebral hemispheres, diencephalons and halves of
      the brain stem were injected with India ink mixture or methylmethacrylate, and
      microdissection was performed or the vascular casts were produced and examined
      under the sterescopic microscope. RESULTS: It was noticed that the perforators
      ranged from 0 to 14 in number, with the smallest mean value (1.1) for the
      diencephalic perforators and the largest one (8.1) for the lenticulostriate
      arteries. The smallest mean diameter (175 MUm) was found in the group of the
      perforators of the anterior communicating artery, whereas the largest one is
      related to the Heubner's artery (668 MUm), the diencephalic thalamoperforating
      vessels (562 MUm), the premamillary vessel (489 MUm) and the lenticulostriate
      arteries (469 MUm). The perforators most frequently originated from the pial
      branches of the basilar artery (91.7 %) and of the posterior cerebral artery
      (59.4 %). The common stems were most often formed by the perforators of the
      basilar (79.2 %), posterior cerebral (75.0 %) and middle cerebral arteries (40.6
      %). Some perforators arose close to or from the terminal divisions, the branching
      sites or the junctions of the parent arteries, where the saccular aneurysms most
      often develop. The anastomoses among the perforators were present in a range from
      6.3 % to 53.2 %. CONCLUSIONS: The micro-anatomical data obtained may be useful
      for neurosurgeons when operating at the base of the brain, as well as for a
      neurological and radiological evaluation of the perforators in the occlusive
      cerebrovascular disease, or in the cases of an aneurysm, arteriovenous
      malformation (AVM) or tumour presence.

PMID- 25772346
TI  - The suboccipital midline approach to foramen magnum meningiomas.
AB  - BACKGROUND: Anterior and anterolateral meningiomas of the foramen magnum (FM) can
      be resected either through extensive skull base approaches or through the
      classical suboccipital midline approach with limited bone removal. METHOD: This
      paper describes the suboccipital midline approach focusing on some peculiar
      technical features that serve to achieve the necessary space for safe resection
      of these challenging tumors. CONCLUSIONS: In our experience, by adopting
      appropriate strategies to gain space (some of them natural, others acquired) the
      suboccipital midline approach can achieve the safe resection of anterior and
      anterolateral FM meningiomas in the majority of cases.

PMID- 25772347
TI  - Purse-string double-layer closure for cesarean incision (Turan technique): Some
      concerns.

PMID- 25772348
TI  - Bottom-up formation of robust gold carbide.
AB  - A new phenomenon of structural reorganization is discovered and characterized for
      a gold-carbon system by in-situ atomic-resolution imaging at temperatures up to
      1300 K. Here, a graphene sheet serves in three ways, as a quasi transparent
      substrate for aberration-corrected high-resolution transmission electron
      microscopy, as an in-situ heater, and as carbon supplier. The sheet has been
      decorated with gold nanoislands beforehand. During electron irradiation at 80 kV
      and at elevated temperatures, the accumulation of gold atoms has been observed on
      defective graphene sites or edges as well as at the facets of gold nanocrystals.
      Both resulted in clustering, forming unusual crystalline structures. Their
      lattice parameters and surface termination differ significantly from standard
      gold nanocrystals. The experimental data, supported by electron energy loss
      spectroscopy and density-functional theory calculations, suggests that isolated
      gold and carbon atoms form - under conditions of heat and electron irradiation -
      a novel type of compound crystal, Au-C in zincblende structure. The novel
      material is metastable, but surprisingly robust, even under annealing condition.

PMID- 25772349
TI  - Acid-stable peroxoniobophosphate clusters to make patterned films.
AB  - Two new peroxoniobophosphate clusters were isolated as tetramethylammonium (TMA)
      salts having the stoichiometries: TMA5[HNb4P2O14(O2)4]?9 H2O and
      TMA3[H7Nb6P4O24(O2)6]?7 H2O. The former is stable over the pH range: 3<pH<12 and
      the latter is stable only below pH 3. These two molecules interconvert as a
      function of solution pH. The [H7Nb6P4O24(O2)6](3-) cluster can be used to
      fabricate patterned niobium phosphate films by electron-beam lithography after
      solution deposition.

PMID- 25772350
TI  - Predictors of breastfeeding duration for rural women in a high-income country:
      evidence from a cohort study.
AB  - AIM: To determine the prevalence of exclusive and 'any breastfeeding' at six
      months in rural Western Australia and to identify the predictors of exclusive and
      'any breastfeeding' duration up to 12 months. METHODS: A total of 427 mothers
      (52% of those contacted) were recruited from maternity services in rural WA and
      asked to complete a baseline questionnaire. Mothers were recontacted at 4, 6, 10,
      16, 26, 32, 40 and 52 weeks to determine factors associated with feeding
      practices. RESULTS: Smoking during pregnancy was the strongest predictor of
      exclusive breastfeeding cessation before six months (aHR 3.21, 95% CI 1.89,
      5.46). A favourable attitude towards breastfeeding, a body mass index of <30 and
      a return to work after six months were associated with reduced risk of
      breastfeeding cessation before both six and 12 months. CONCLUSION: Breastfeeding
      duration in rural Western Australia is influenced by modifiable factors such as
      smoking during pregnancy and prepregnancy obesity, therefore strategies to
      address these risk factors in rural women prior to delivery may contribute to
      improved breastfeeding rates.

PMID- 25772351
TI  - Direct Visualization Reveals Kinetics of Meiotic Chromosome Synapsis.
AB  - The synaptonemal complex (SC) is a conserved protein complex that stabilizes
      interactions along homologous chromosomes (homologs) during meiosis. The SC
      regulates genetic exchanges between homologs, thereby enabling reductional
      division and the production of haploid gametes. Here, we directly observe SC
      assembly (synapsis) by optimizing methods for long-term fluorescence recording in
      C. elegans. We report that synapsis initiates independently on each chromosome
      pair at or near pairing centers-specialized regions required for homolog
      associations. Once initiated, the SC extends rapidly and mostly irreversibly to
      chromosome ends. Quantitation of SC initiation frequencies and extension rates
      reveals that initiation is a rate-limiting step in homolog interactions.
      Eliminating the dynein-driven chromosome movements that accompany synapsis
      severely retards SC extension, revealing a new role for these conserved motions.
      This work provides the first opportunity to directly observe and quantify key
      aspects of meiotic chromosome interactions and will enable future in vivo
      analysis of germline processes.

PMID- 25772352
TI  - Axis Patterning by BMPs: Cnidarian Network Reveals Evolutionary Constraints.
AB  - BMP signaling plays a crucial role in the establishment of the dorso-ventral body
      axis in bilaterally symmetric animals. However, the topologies of the bone
      morphogenetic protein (BMP) signaling networks vary drastically in different
      animal groups, raising questions about the evolutionary constraints and
      evolvability of BMP signaling systems. Using loss-of-function analysis and
      mathematical modeling, we show that two signaling centers expressing different
      BMPs and BMP antagonists maintain the secondary axis of the sea anemone
      Nematostella. We demonstrate that BMP signaling is required for asymmetric Hox
      gene expression and mesentery formation. Computational analysis reveals that
      network parameters related to BMP4 and Chordin are constrained both in
      Nematostella and Xenopus, while those describing the BMP signaling modulators can
      vary significantly. Notably, only chordin, but not bmp4 expression needs to be
      spatially restricted for robust signaling gradient formation. Our data provide an
      explanation of the evolvability of BMP signaling systems in axis formation
      throughout Eumetazoa.

PMID- 25772353
TI  - A Lupus-Associated Mac-1 Variant Has Defects in Integrin Allostery and
      Interaction with Ligands under Force.
AB  - Leukocyte CD18 integrins increase their affinity for ligand by transmitting
      allosteric signals to and from their ligand-binding alphaI domain. Mechanical
      forces induce allosteric changes that paradoxically slow dissociation by
      increasing the integrin/ligand bond lifetimes, referred to as catch bonds. Mac-1
      formed catch bonds with its ligands. However, a Mac-1 gene (ITGAM) coding variant
      (rs1143679, R77H), which is located in the beta-propeller domain and is
      significantly associated with systemic lupus erythematosus risk, exhibits a
      marked impairment in 2D ligand affinity and affinity maturation under mechanical
      force. Targeted mutations and activating antibodies reveal that the failure in
      Mac-1 R77H allostery is rescued by induction of cytoplasmic tail separation and
      full integrin extension. These findings demonstrate roles for R77, and the beta
      propeller in which it resides, in force-induced allostery relay and integrin bond
      stabilization. Defects in these processes may have pathological consequences, as
      the Mac-1 R77H variant is associated with increased susceptibility to lupus.

PMID- 25772354
TI  - The N-Terminal Domain of SIRT1 Is a Positive Regulator of Endogenous SIRT1
      Dependent Deacetylation and Transcriptional Outputs.
AB  - The NAD+-dependent protein deacetylase SIRT1 regulates energy metabolism,
      responses to stress, and aging by deacetylating many different proteins,
      including histones and transcription factors. The mechanisms controlling SIRT1
      enzymatic activity are complex and incompletely characterized, yet essential for
      understanding how to develop therapeutics that target SIRT1. Here, we demonstrate
      that the N-terminal domain of SIRT1 (NTERM) can trans-activate deacetylation
      activity by physically interacting with endogenous SIRT1 and promoting its
      association with the deacetylation substrate NF-kappaB p65. Two motifs within the
      NTERM domain contribute to activation of SIRT1-dependent activities, and
      expression of one of these motifs in mice is sufficient to lower fasting glucose
      levels and improve glucose tolerance in a manner similar to overexpression of
      SIRT1. Our results provide insights into the regulation of SIRT1 activity and a
      rationale for pharmacological control of SIRT1-dependent activities.

PMID- 25772355
TI  - Short Inverted Repeats Are Hotspots for Genetic Instability: Relevance to Cancer
      Genomes.
AB  - Analyses of chromosomal aberrations in human genetic disorders have revealed that
      inverted repeat sequences (IRs) often co-localize with endogenous chromosomal
      instability and breakage hotspots. Approximately 80% of all IRs in the human
      genome are short (<100 bp), yet the mutagenic potential of such short cruciform
      forming sequences has not been characterized. Here, we find that short IRs are
      enriched at translocation breakpoints in human cancer and stimulate the formation
      of DNA double-strand breaks (DSBs) and deletions in mammalian and yeast cells. We
      provide evidence for replication-related mechanisms of IR-induced genetic
      instability and a novel XPF cleavage-based mechanism independent of DNA
      replication. These discoveries implicate short IRs as endogenous sources of DNA
      breakage involved in disease etiology and suggest that these repeats represent a
      feature of genome plasticity that may contribute to the evolution of the human
      genome by providing a means for diversity within the population.

PMID- 25772356
TI  - Tetracyclines Disturb Mitochondrial Function across Eukaryotic Models: A Call for
      Caution in Biomedical Research.
AB  - In recent years, tetracyclines, such as doxycycline, have become broadly used to
      control gene expression by virtue of the Tet-on/Tet-off systems. However, the
      wide range of direct effects of tetracycline use has not been fully appreciated.
      We show here that these antibiotics induce a mitonuclear protein imbalance
      through their effects on mitochondrial translation, an effect that likely
      reflects the evolutionary relationship between mitochondria and proteobacteria.
      Even at low concentrations, tetracyclines induce mitochondrial proteotoxic
      stress, leading to changes in nuclear gene expression and altered mitochondrial
      dynamics and function in commonly used cell types, as well as worms, flies, mice,
      and plants. Given that tetracyclines are so widely applied in research,
      scientists should be aware of their potentially confounding effects on
      experimental results. Furthermore, these results caution against extensive use of
      tetracyclines in livestock due to potential downstream impacts on the environment
      and human health.

PMID- 25772358
TI  - cKit Lineage Hemogenic Endothelium-Derived Cells Contribute to Mesenteric
      Lymphatic Vessels.
AB  - Pathological lymphatic diseases mostly affect vessels in specific tissues, yet
      little is known about organ-specific regulation of the lymphatic vasculature.
      Here, we show that the vascular endothelial growth factor receptor 3 (VEGFR
      3)/p110alpha PI3-kinase signaling pathway is selectively required for the
      formation of mesenteric lymphatic vasculature. Using genetic lineage tracing, we
      demonstrate that part of the mesenteric lymphatic vasculature develops from cKit
      lineage cells of hemogenic endothelial origin through a process we define as
      lymphvasculogenesis. This is contrary to the current dogma that all mammalian
      lymphatic vessels form by sprouting from veins. Our results reveal vascular-bed
      specific differences in the origin and mechanisms of vessel formation, which may
      critically underlie organ-specific manifestation of lymphatic dysfunction in
      disease. The progenitor cells identified in this study may be exploited to
      restore lymphatic function following cancer surgery, lymphedema, or tissue
      trauma.

PMID- 25772357
TI  - YAP Inhibition Restores Hepatocyte Differentiation in Advanced HCC, Leading to
      Tumor Regression.
AB  - Defective Hippo/YAP signaling in the liver results in tissue overgrowth and
      development of hepatocellular carcinoma (HCC). Here, we uncover mechanisms of YAP
      mediated hepatocyte reprogramming and HCC pathogenesis. YAP functions as a
      rheostat in maintaining metabolic specialization, differentiation, and quiescence
      within the hepatocyte compartment. Increased or decreased YAP activity reprograms
      subsets of hepatocytes to different fates associated with deregulation of the
      HNF4A, CTNNB1, and E2F transcriptional programs that control hepatocyte
      quiescence and differentiation. Importantly, treatment with small interfering RNA
      lipid nanoparticles (siRNA-LNPs) targeting YAP restores hepatocyte
      differentiation and causes pronounced tumor regression in a genetically
      engineered mouse HCC model. Furthermore, YAP targets are enriched in an
      aggressive human HCC subtype characterized by a proliferative signature and
      absence of CTNNB1 mutations. Thus, our work reveals Hippo signaling as a key
      regulator of the positional identity of hepatocytes, supports targeting of YAP
      using siRNA-LNPs as a paradigm of differentiation-based therapy, and identifies
      an HCC subtype that is potentially responsive to this approach.

PMID- 25772359
TI  - MAPK Phosphatase 5 Expression Induced by Influenza and Other RNA Virus Infection
      Negatively Regulates IRF3 Activation and Type I Interferon Response.
AB  - The type I interferon system is essential for antiviral immune response and is a
      primary target of viral immune evasion strategies. Here, we show that virus
      infection induces the expression of MAPK phosphatase 5 (MKP5), a dual-specificity
      phosphatase (DUSP), in host cells. Mice deficient in MKP5 were resistant to H1N1
      influenza infection, which is associated with increased IRF3 activation and type
      I interferon expression in comparison with WT mice. Increased type I interferon
      responses were also observed in MKP5-deficient cells and animals upon other RNA
      virus infection, including vesicular stomatitis virus and sendai virus. These
      observations were attributed to the ability of MKP5 to interact with and
      dephosphorylate IRF3. Our study reveals a critical function of a DUSP in negative
      regulation of IRF3 activity and demonstrates a mechanism by which influenza and
      other RNA viruses inhibit type I interferon response in the host through MKP5.

PMID- 25772361
TI  - FBH1 Catalyzes Regression of Stalled Replication Forks.
AB  - DNA replication fork perturbation is a major challenge to the maintenance of
      genome integrity. It has been suggested that processing of stalled forks might
      involve fork regression, in which the fork reverses and the two nascent DNA
      strands anneal. Here, we show that FBH1 catalyzes regression of a model
      replication fork in vitro and promotes fork regression in vivo in response to
      replication perturbation. Cells respond to fork stalling by activating checkpoint
      responses requiring signaling through stress-activated protein kinases.
      Importantly, we show that FBH1, through its helicase activity, is required for
      early phosphorylation of ATM substrates such as CHK2 and CtIP as well as
      hyperphosphorylation of RPA. These phosphorylations occur prior to apparent DNA
      double-strand break formation. Furthermore, FBH1-dependent signaling promotes
      checkpoint control and preserves genome integrity. We propose a model whereby
      FBH1 promotes early checkpoint signaling by remodeling of stalled DNA replication
      forks.

PMID- 25772360
TI  - Developmentally Regulated Post-translational Modification of Nucleoplasmin
      Controls Histone Sequestration and Deposition.
AB  - Nucleoplasmin (Npm) is an abundant histone chaperone in vertebrate oocytes and
      embryos. During embryogenesis, regulation of Npm histone binding is critical for
      its function in storing and releasing maternal histones to establish and maintain
      the zygotic epigenome. Here, we demonstrate that Xenopus laevis Npm post
      translational modifications (PTMs) specific to the oocyte and egg promote either
      histone deposition or sequestration, respectively. Mass spectrometry and Npm
      phosphomimetic mutations used in chromatin assembly assays identified
      hyperphosphorylation on the N-terminal tail as a critical regulator for
      sequestration. C-terminal tail phosphorylation and PRMT5-catalyzed arginine
      methylation enhance nucleosome assembly by promoting histone interaction with the
      second acidic tract of Npm. Electron microscopy reconstructions of Npm and TTLL4
      activity toward the C-terminal tail demonstrate that oocyte- and egg-specific
      PTMs cause Npm conformational changes. Our results reveal that PTMs regulate Npm
      chaperoning activity by modulating Npm conformation and Npm-histone interaction,
      leading to histone sequestration in the egg.

PMID- 25772362
TI  - De-convoluting the Genetic Adaptations of E. coli C41(DE3) in Real Time Reveals
      How Alleviating Protein Production Stress Improves Yields.
AB  - The well-established E. coli protein production strain C41(DE3) was isolated from
      the T7 RNA polymerase-based BL21(DE3) strain for its ability to produce difficult
      recombinant proteins, and it acquired multiple mutations during its isolation.
      Standard allelic replacement and competition experiments were insufficient to de
      convolute these mutations. By reconstructing the evolution of C41(DE3) in real
      time, we identified the time frames when the different mutations occurred,
      enabling us to link them to particular stress events. Starvation stress imposed
      by the isolation procedure selected for mutations enhancing nutrient uptake, and
      protein production stress for mutations weakening the lacUV5 promoter, which
      governs t7rnap expression. Moreover, recapitulating protein production stress in
      BL21(DE3) showed that mutations weakening the lacUV5 promoter occur through RecA
      dependent recombination with the wild-type lac-promoter and are selected for upon
      the production of any protein. Thus, the instability of the lacUV5 promoter in
      BL21(DE3) alleviates protein production stress and can be harnessed to enhance
      production.

PMID- 25772363
TI  - Dynamic Visualization of mTORC1 Activity in Living Cells.
AB  - The mechanistic target of rapamycin complex 1 (mTORC1) senses diverse signals to
      regulate cell growth and metabolism. It has become increasingly clear that mTORC1
      activity is regulated in time and space inside the cell, but direct interrogation
      of such spatiotemporal regulation is challenging. Here, we describe a genetically
      encoded mTORC1 activity reporter (TORCAR) that exhibits a change in FRET in
      response to phosphorylation by mTORC1. Co-imaging mTORC1 activity and calcium
      dynamics revealed that a growth-factor-induced calcium transient contributes to
      mTORC1 activity. Dynamic activity maps generated with the use of subcellularly
      targeted TORCAR uncovered mTORC1 activity not only in cytosol and at the lysosome
      but also in the nucleus and at the plasma membrane. Furthermore, a wide
      distribution of activities was observed upon growth factor stimulation, whereas
      leucine ester, an amino acid surrogate, induces more compartmentalized activities
      at the lysosome and in the nucleus. Thus, mTORC1 activities are spatiotemporally
      regulated in a signal-specific manner.

PMID- 25772364
TI  - SUMO-2 Orchestrates Chromatin Modifiers in Response to DNA Damage.
AB  - Small ubiquitin-like modifiers play critical roles in the DNA damage response
      (DDR). To increase our understanding of SUMOylation in the mammalian DDR, we
      employed a quantitative proteomics approach in order to identify dynamically
      regulated SUMO-2 conjugates and modification sites upon treatment with the DNA
      damaging agent methyl methanesulfonate (MMS). We have uncovered a dynamic set of
      20 upregulated and 33 downregulated SUMO-2 conjugates, and 755 SUMO-2 sites, of
      which 362 were dynamic in response to MMS. In contrast to yeast, where a response
      is centered on homologous recombination, we identified dynamically SUMOylated
      interaction networks of chromatin modifiers, transcription factors, DNA repair
      factors, and nuclear body components. SUMOylated chromatin modifiers include
      JARID1B/KDM5B, JARID1C/KDM5C, p300, CBP, PARP1, SetDB1, and MBD1. Whereas
      SUMOylated JARID1B was ubiquitylated by the SUMO-targeted ubiquitin ligase RNF4
      and degraded by the proteasome in response to DNA damage, JARID1C was SUMOylated
      and recruited to the chromatin to demethylate histone H3K4.

PMID- 25772365
TI  - XIRP2, an actin-binding protein essential for inner ear hair-cell stereocilia.
AB  - Hair cells of the inner ear are mechanoreceptors for hearing and balance, and
      proteins highly enriched in hair cells may have specific roles in the development
      and maintenance of the mechanotransduction apparatus. We identified
      XIRP2/mXinbeta as an enriched protein likely to be essential for hair cells. We
      found that different isoforms of this protein are expressed and differentially
      located: short splice forms (also called XEPLIN) are targeted more to
      stereocilia, whereas two long isoforms containing a XIN-repeat domain are in both
      stereocilia and cuticular plates. Mice lacking the Xirp2 gene developed normal
      stereocilia bundles, but these degenerated with time: stereocilia were lost and
      long membranous protrusions emanated from the nearby apical surfaces. At an
      ultrastructural level, the paracrystalline actin filaments became disorganized.
      XIRP2 is apparently involved in the maintenance of actin structures in
      stereocilia and cuticular plates of hair cells, and perhaps in other organs where
      it is expressed.

PMID- 25772368
TI  - Time profiles and toxicokinetic parameters of key biomarkers of exposure to
      cypermethrin in orally exposed volunteers compared with previously available
      kinetic data following permethrin exposure.
AB  - Biomonitoring of pyrethroid exposure is largely conducted but human
      toxicokinetics has not been fully documented. This is essential for a proper
      interpretation of biomonitoring data. Time profiles and toxicokinetic parameters
      of key biomarkers of exposure to cypermethrin in orally exposed volunteers have
      been documented and compared with previously available kinetic data following
      permethrin dosing. Six volunteers ingested 0.1 mg kg(-1) bodyweight of
      cypermethrin acutely. The same volunteers were exposed to permethrin earlier.
      Blood samples were taken over 72 h after treatment and complete timed urine voids
      were collected over 84 h postdosing. Cis- and trans-3-(2,2-dichlorovinyl)-2,2
      dimethylcyclopropane-1-carboxylic acids (trans- and cis-DCCA) and 3
      phenoxybenzoic acid (3-PBA) metabolites, common to both cypermethrin and
      permethrin, were quantified. Blood and urinary time courses of all three
      metabolites were similar following cypermethrin and permethrin exposure. Plasma
      levels of metabolites reached peak values on average ~ 5-7 h post-dosing; the
      elimination phase showed mean apparent half-lives (t1/2 ) for trans-DCCA, cis
      DCCA and 3-PBA of 5.1, 6.9 and 9.2 h, respectively, following cypermethrin
      treatment as compared to 7.1, 6.2 and 6.5 h after permethrin dosing.
      Corresponding mean values obtained from urinary rate time courses were peak
      values at ~ 9 h post-dosing and apparent elimination t1/2 of 6.3, 6.4 and 6.4 h
      for trans-DCCA, cis-DCCA and 3-PBA, respectively, following cypermethrin
      treatment as compared to 5.4, 4.5 and 5.7 h after permethrin dosing. These data
      confirm that the kinetics of cypermethrin is similar to that of permethrin in
      humans and that their common biomarkers of exposure may be used for an overall
      assessment of exposure.

PMID- 25772366
TI  - Mouse low-grade gliomas contain cancer stem cells with unique molecular and
      functional properties.
AB  - The availability of adult malignant glioma stem cells (GSCs) has provided
      unprecedented opportunities to identify the mechanisms underlying treatment
      resistance. Unfortunately, there is a lack of comparable reagents for the study
      of pediatric low-grade glioma (LGG). Leveraging a neurofibromatosis 1 (Nf1)
      genetically engineered mouse LGG model, we report the isolation of CD133(+) multi
      potent low-grade glioma stem cells (LG-GSCs), which generate glioma-like lesions
      histologically similar to the parent tumor following injection into
      immunocompetent hosts. In addition, we demonstrate that these LG-GSCs harbor
      selective resistance to currently employed conventional and biologically targeted
      anti-cancer agents, which reflect the acquisition of new targetable signaling
      pathway abnormalities. Using transcriptomic analysis to identify additional
      molecular properties, we discovered that mouse and human LG-GSCs harbor high
      levels of Abcg1 expression critical for protecting against ER-stress-induced
      mouse LG-GSC apoptosis. Collectively, these findings establish that LGG cancer
      stem cells have unique molecular and functional properties relevant to brain
      cancer treatment.

PMID- 25772367
TI  - Targeted Germline Modifications in Rats Using CRISPR/Cas9 and Spermatogonial Stem
      Cells.
AB  - Organisms with targeted genomic modifications are efficiently produced by gene
      editing in embryos using CRISPR/Cas9 RNA-guided DNA endonuclease. Here, to
      facilitate germline editing in rats, we used CRISPR/Cas9 to catalyze targeted
      genomic mutations in rat spermatogonial stem cell cultures. CRISPR/Cas9-modified
      spermatogonia regenerated spermatogenesis and displayed long-term sperm-forming
      potential following transplantation into rat testes. Targeted germline mutations
      in Epsti1 and Erbb3 were vertically transmitted from recipients to exclusively
      generate "pure," non-mosaic mutant progeny. Epsti1 mutant rats were produced with
      or without genetic selection of donor spermatogonia. Monoclonal enrichment of
      Erbb3 null germlines unmasked recessive spermatogenesis defects in culture that
      were buffered in recipients, yielding mutant progeny isogenic at targeted
      alleles. Thus, spermatogonial gene editing with CRISPR/Cas9 provided a platform
      for generating targeted germline mutations in rats and for studying
      spermatogenesis.

PMID- 25772369
TI  - Simultaneous multi-vessel coronary thrombosis in patients with ST-elevation
      myocardial infarction: a systematic review.
AB  - Acute ST-elevation myocardial infarction (STEMI) with simultaneous multiple
      coronary thrombosis has been described, however; the available information about
      the clinical presentation and management of this condition is scarce. We searched
      the Medline and Web of Science databases from 1990 until August 2014 for all case
      reports, case series, and observational studies that reported simultaneous multi
      vessel thrombosis at the time of the primary percutaneous coronary intervention
      (PCI). We excluded the articles that reported an identifiable cause for coronary
      thrombosis. A total of 29 articles were retrieved yielding 56 patients. Patients
      were predominantly males (88%) with a mean age of 59 years. Cardiogenic shock was
      the predominant presentation (41%). Simultaneous thrombosis of the left anterior
      descending and right coronary arteries was the commonest angiographic finding
      (50%). Primary PCI was the main treatment modality and an intra-aortic balloon
      pump was utilized in 38% of the cases. The in-hospital mortality was 5%.
      Simultaneous multi-vessel thrombosis at the time of STEMI presents a rare
      condition. The cases reported in the literature presented with a high incidence
      of cardiogenic shock. Larger studies are needed to address the proper management
      and evaluate the outcomes associated with this condition. 

PMID- 25772371
TI  - Uptake of perfluoroalkyl acids in the leaves of coniferous and deciduous broad
      leaved trees.
AB  - Analytical methods for determining perfluoroalkyl acids (PFAAs) in leaves were
      developed to quantify a suite of analytes in both coniferous and deciduous broad
      leaved trees. Sodium hydroxide-methanol and solid-phase extraction was selected
      as the extracting and cleanup strategy for PFAA analysis. Ten perfluorocarboxylic
      acids (PFCAs) and 4 perfluorosulfonic acids (PFSAs) were monitored in 7 kinds of
      leaves grown in the urban areas of Dalian, China. The results show that
      coniferous tree leaves take up more PFAAs than broad-leaved tree leaves, with the
      highest amount of 150 ng/g in pine needles. Leaf PFCA levels were much higher
      than PFSAs level. Short carbon-chain PFCAs with 3 to 6 perfluorinated carbons
      account for approximately 40% to 80% of the total leaf PFAAs, where uptake
      decreased with increasing carbon chain length. Temporal observation of leaf PFAAs
      revealed no significant variation of concentrations in the leaves over a weekly
      interval and the absence of significant seasonal change in pine needles and
      sophora. The present study provides some evidence for the accumulation of PFAAs
      in leaves, which is valuable for understanding their environmental behavior and
      the development of alternative bioindicator.

PMID- 25772370
TI  - Highly Predictive Reprogramming of tRNA Modifications Is Linked to Selective
      Expression of Codon-Biased Genes.
AB  - Cells respond to stress by controlling gene expression at several levels, with
      little known about the role of translation. Here, we demonstrate a coordinated
      translational stress response system involving stress-specific reprogramming of
      tRNA wobble modifications that leads to selective translation of codon-biased
      mRNAs representing different classes of critical response proteins. In budding
      yeast exposed to four oxidants and five alkylating agents, tRNA modification
      patterns accurately distinguished among chemically similar stressors, with 14
      modified ribonucleosides forming the basis for a data-driven model that predicts
      toxicant chemistry with >80% sensitivity and specificity. tRNA modification
      subpatterns also distinguish SN1 from SN2 alkylating agents, with SN2-induced
      increases in m(3)C in tRNA mechanistically linked to selective translation of
      threonine-rich membrane proteins from genes enriched with ACC and ACT degenerate
      codons for threonine. These results establish tRNA modifications as predictive
      biomarkers of exposure and illustrate a novel regulatory mechanism for
      translational control of cell stress response. 

PMID- 25772372
TI  - Designing lipids for selective partitioning into liquid ordered membrane domains.
AB  - Self-organization of lipid molecules into specific membrane phases is key to the
      development of hierarchical molecular assemblies that mimic cellular structures.
      While the packing interaction of the lipid tails should provide the major driving
      force to direct lipid partitioning to ordered or disordered membrane domains,
      numerous examples show that the headgroup and spacer play important but undefined
      roles. We report here the development of several new biotinylated lipids that
      examine the role of spacer chemistry and structure on membrane phase
      partitioning. The new lipids were prepared with varying lengths of low molecular
      weight polyethylene glycol (EGn) spacers to examine how spacer hydrophilicity and
      length influence their partitioning behavior following binding with FITC-labeled
      streptavidin in liquid ordered (Lo) and liquid disordered (Ld) phase coexisting
      membranes. Partitioning coefficients (Kp Lo/Ld) of the biotinylated lipids were
      determined using fluorescence measurements in studies with giant unilamellar
      vesicles (GUVs). Compared against DPPE-biotin, DPPE-cap-biotin, and DSPE-PEG2000
      biotin lipids, the new dipalmityl-EGn-biotin lipids exhibited markedly enhanced
      partitioning into liquid ordered domains, achieving Kp of up to 7.3 with a
      decaethylene glycol spacer (DP-EG10-biotin). We further demonstrated biological
      relevance of the lipids with selective partitioning to lipid raft-like domains
      observed in giant plasma membrane vesicles (GPMVs) derived from mammalian cells.
      Our results found that the spacer group not only plays a pivotal role for
      designing lipids with phase selectivity but may also influence the structural
      order of the domain assemblies. 

PMID- 25772373
TI  - Estimating the survival function based on the semi-Markov model for dependent
      censoring.
AB  - In this paper, we study a nonparametric maximum likelihood estimator (NPMLE) of
      the survival function based on a semi-Markov model under dependent censoring. We
      show that the NPMLE is asymptotically normal and achieves asymptotic
      nonparametric efficiency. We also provide a uniformly consistent estimator of the
      corresponding asymptotic covariance function based on an information operator.
      The finite-sample performance of the proposed NPMLE is examined with simulation
      studies, which show that the NPMLE has smaller mean squared error than the
      existing estimators and its corresponding pointwise confidence intervals have
      reasonable coverages. A real example is also presented. 

PMID- 25772374
TI  - Proportional exponentiated link transformed hazards (ELTH) models for discrete
      time survival data with application.
AB  - Discrete survival data are routinely encountered in many fields of study
      including behavior science, economics, epidemiology, medicine, and social
      science. In this paper, we develop a class of proportional exponentiated link
      transformed hazards (ELTH) models. We carry out a detailed examination of the
      role of links in fitting discrete survival data and estimating regression
      coefficients. Several interesting results are established regarding the choice of
      links and baseline hazards. We also characterize the conditions for improper
      survival functions and the conditions for existence of the maximum likelihood
      estimates under the proposed ELTH models. An extensive simulation study is
      conducted to examine the empirical performance of the parameter estimates under
      the Cox proportional hazards model by treating discrete survival times as
      continuous survival times, and the model comparison criteria, AIC and BIC, in
      determining links and baseline hazards. A SEER breast cancer dataset is analyzed
      in details to further demonstrate the proposed methodology. 

PMID- 25772375
TI  - Risk of transmission of human T-lymphotropic virus through transplant.

PMID- 25772376
TI  - Next-generation diagnostics: gene panel, exome, or whole genome?
AB  - Although the benefits of next-generation sequencing (NGS) for the diagnosis of
      heterogeneous diseases such as intellectual disability (ID) are undisputed, there
      is little consensus on the relative merits of targeted enrichment, whole-exome
      sequencing (WES) or whole-genome sequencing (WGS). To answer this question, WES
      and WGS data from the same nine samples were compared, and WES was shown not to
      miss any variants identified by WGS in a gene panel including ~500 genes linked
      to ID (500GP). Additionally, deeply sequenced WES data were shown to adequately
      cover ~99% of the 500GP; thus, little additional benefit was to be expected from
      a targeted enrichment approach. To reduce costs, minimal sequencing criteria were
      determined by investigating the relation between sequenced reads and outcome
      parameters such as coverage and variant yield. Our analysis indicated that 60
      million reads yielded a mean coverage of ~60*: ~97% of the 500GP sequences were
      sufficiently covered to exclude variants, whereas variant yield was ~99.5% and
      false-positive and false-negative rates were controlled. Our findings indicate
      that WES is currently the optimal approach to ID diagnostics. This result depends
      on the capture kit and sequencing strategy used. The developed framework however
      is amenable to other sequencing approaches.

PMID- 25772377
TI  - Na4IrO4 : square-planar coordination of a transition metal in d(5) configuration
      due to weak on-site coulomb interactions.
AB  - Local environments and valence electron counts primarily determine the electronic
      states and physical properties of transition-metal complexes. For example, square
      planar coordination geometries found in transition-metal oxometalates such as
      cuprates are usually associated with the d(8)  or d(9)  electron configuration.
      In this work, we address an unusual square-planar single oxoanionic [IrO4 ](4-) 
      species, as observed in Na4 IrO4 in which Ir(IV) has a d(5)  configuration, and
      characterize the chemical bonding through experiments and by ab initio
      calculations. We find that the Ir(IV)  center in ground-state Na4 IrO4 has square
      planar coordination geometry because of the weak Coulomb repulsion of the Ir-5d
      electrons. In contrast, in its 3d counterpart Na4 CoO4 , the Co(IV) center is
      tetrahedrally coordinated because of strong electron correlation. Na4 IrO4 may
      thus serve as a simple yet important example to study the ramifications of
      Hubbard-type Coulomb interactions on local geometries. 

PMID- 25772378
TI  - Overuse of imaging the male breast-findings in 557 patients.
AB  - Gynecomastia is the most common abnormality of the male breast. However, breast
      cancer may occur, albeit with a significantly lower incidence than in females.
      Imaging is often used as part of the diagnosis. The aim of this study was to
      assess the utilization and outcome of imaging with mammography or ultrasound of
      the male breast in a university hospital's department of radiology. A
      retrospective study assessing the imaging of the male breast in 557 patients over
      a 10-year period. Referral was done mainly by general surgeons and general
      practitioners. The most common indication was enlargement of the breast,
      described as gynecomastia or swelling in 74% of patients, followed by pain in 24%
      and "lumps" in 10%. The modalities used were mammography in 65%, ultrasound in
      51% and both in 26%. Most examinations, 519, were BI-RADS 1 or 2, and 38 were BI
      RADS 3 or higher. Altogether 160 patients had additional fine-needle aspiration
      or biopsy. Malignancies were diagnosed in five patients (0.89%). Imaging had a
      sensitivity of 80% and a specificity of 99%. The positive predictive value was
      44% and the negative predictive value 99.8%. Malignancies are rare in the male
      breast. The probability of finding cancer when performing imaging of clinically
      benign findings in the male breast is negligible. Imaging is not warranted unless
      there are suspicious abnormalities. Routine imaging of gynecomastia should be
      discouraged. 

PMID- 25772379
TI  - Circadian Clock Genes Universally Control Key Agricultural Traits.
AB  - Circadian clocks are endogenous timers that enable plants to synchronize
      biological processes with daily and seasonal environmental conditions in order to
      allocate resources during the most beneficial times of day and year. The
      circadian clock regulates a number of central plant activities, including growth,
      development, and reproduction, primarily through controlling a substantial
      proportion of transcriptional activity and protein function. This review examines
      the roles that alleles of circadian clock genes have played in domestication and
      improvement of crop plants. The focus here is on three groups of circadian clock
      genes essential to clock function in Arabidopsis thaliana: PSEUDO-RESPONSE
      REGULATORs, GIGANTEA, and the evening complex genes early flowering 3, early
      flowering 4, and lux arrhythmo. homologous genes from each group underlie
      quantitative trait loci that have beneficial influences on key agricultural
      traits, especially flowering time but also yield, biomass, and biennial growth
      habit. Emerging insights into circadian clock regulation of other fundamental
      plant processes, including responses to abiotic and biotic stresses, are
      discussed to highlight promising avenues for further crop improvement.

PMID- 25772380
TI  - Selective dysfunction of basal ganglia subterritories: From movement to
      behavioral disorders.
AB  - Historically, Parkinson's disease (PD) was defined as a pure movement disorder.
      Currently, it is widely accepted that this disease is also characterized by
      nonmotor signs, such as depression, apathy, and anxiety. On the other hand, the
      consideration of Gilles de la Tourette syndrome (GTS) as a neuropsychiatric
      disorder has also been debated. In this review, we will focus on these two
      disorders, which combine both motor and behavioral features and in which
      dysfunction of cortical and subcortical regions was suggested. Anatomical,
      experimental, and clinical data are reported to support the involvement of basal
      ganglia (BG) in cognitive and motivational functions in addition to motor
      control. In PD, the nonmotor signs could result from the heterogeneity of
      dopaminergic lesions and excessive activation of the dopamine receptors,
      particularly within the limbic neuronal networks. Experimental results obtained
      on nonhuman primates using local disinhibition within functional territories of
      BG allowed the precise mapping of their motor and nonmotor functions. Thus,
      impairment of inhibitory control inside specific striatal territories induced
      behavioral disorders and abnormal movements, which had striking similarities to
      clinical expressions of GTS. Establishing such a relationship between BG
      subterritories and motor and behavioral disorders could potentially be helpful
      for future target choices for DBS in many neuropsychiatric disorders.
      Furthermore, it is also of great interest for therapeutic research and for the
      efficient targeting of symptom relief to determine the precise pharmacological
      effects of the two main modulators of BG function, which are dopamine and
      serotonin.

PMID- 25772382
TI  - Highly selective detection of palladium and picric acid by a luminescent MOF: a
      dual functional fluorescent sensor.
AB  - A Zn(II) based luminescent metal organic framework is synthesized, which acts as
      a dual functional fluorescent sensor to selectively detect picric acid and
      palladium(II).

PMID- 25772381
TI  - Oseltamivir expands quasispecies of influenza virus through cell-to-cell
      transmission.
AB  - The population of influenza virus consists of a huge variety of variants, called
      quasispecies, due to error-prone replication. Previously, we reported that
      progeny virions of influenza virus become infected to adjacent cells via cell-to
      cell transmission pathway in the presence of oseltamivir. During cell-to-cell
      transmission, viruses become infected to adjacent cells at high multiplicity
      since progeny virions are enriched on plasma membrane between infected cells and
      their adjacent cells. Co-infection with viral variants may rescue recessive
      mutations with each other. Thus, it is assumed that the cell-to-cell transmission
      causes expansion of virus quasispecies. Here, we have demonstrated that
      temperature-sensitive mutations remain in progeny viruses even at non-permissive
      temperature by co-infection in the presence of oseltamivir. This is possibly due
      to a multiplex infection through the cell-to-cell transmission by the addition of
      oseltamivir. Further, by the addition of oseltamivir, the number of missense
      mutation introduced by error-prone replication in segment 8 encoding NS1 was
      increased in a passage-dependent manner. The number of missense mutation in
      segment 5 encoding NP was not changed significantly, whereas silent mutation was
      increased. Taken together, we propose that oseltamivir expands influenza virus
      quasispecies via cell-to-cell transmission, and may facilitate the viral
      evolution and adaptation. 

PMID- 25772383
TI  - Systemic changes following carrageenan-induced paw inflammation in rats.
AB  - OBJECTIVE AND DESIGN: Carrageenan-induced paw edema has been described as a local
      and acute inflammatory process. In fact, little is known about the time course
      and systemic changes following a carrageenan injection. In this study, we examine
      the systemic changes that follow carrageenan injection in the paw. METHODS: Acute
      inflammation was produced by subplantar injection of carrageenan in a hind paw of
      Sprague-Dawley rats. Saline was used in control rats. Paw volume was measured
      with a plethysmometer. The hot plate latency test was used to quantify
      antinociception. C-reactive protein (CRP) levels were measured with a sandwich
      enzyme immunoassay. Fibrinogen concentration was measured using the gravimetric
      method. Lung morphometric analysis was performed using an image processing
      package. Lungs and paws were also examined for tissue factor (TF) and
      proinflammatory cytokines expression by immunohistochemistry. RESULTS: We found
      diverse systemic changes including increased levels of acute phase proteins, such
      as CRP and fibrinogen, and a lung inflammatory process characterized by lung
      edema, fibrin deposition, and leukocyte infiltration. An elevated expression of
      TF, IL-6, IL-1beta, and TNFalpha, was observed in paw and lung tissue sections by
      immunohistochemical methods. CONCLUSION: This study provides new evidence that a
      local carrageenan injection induces a systemic response.

PMID- 25772384
TI  - Extraurothelial recurrence after radical nephroureterectomy: preoperative
      predictors and survival.
AB  - OBJECTIVE: To identify the preoperative predictors of extraurothelial recurrence
      (EUR) after radical nephroureterectomy (RNU) in patients with upper tract
      urothelial carcinoma (UTUC). METHODS: A single-center series of 238 consecutive
      patients who were treated with RNU for UTUC was evaluated. Recurrence-free
      probabilities and cancer-specific survival (CSS) were estimated using the Kaplan
      Meier method. Multivariate Cox proportional hazards regression models were used
      to evaluate the association between various clinicopathological factors and EUR.
      RESULTS: The median time to EUR was 17.6 months (range 3-73 months). EUR-free
      survival rates at 1, 3, 5, and 7 years were 87.8, 75.2, 73.5, and 72.6%,
      respectively. In multivariate Cox regression analyses, tumor stage (HR 27.4; 95%
      CI 7.83-95.8; p = 0.0001) and lymphovascular invasion (LVI) (HR 1.53; 95% CI 1.22
      3.12; p = 0.01) were independently associated with EUR. In patients with EUR, 5
      year CSS estimate was 29.2%. Tumor stage (HR 14.3; 95% CI 4.55-45.2; p < 0.001)
      and EUR (HR 2.7; 95% CI 1.54-4.73; p = 0.001) were the only independent
      predictors associated with worse CSS. CONCLUSIONS: EUR significantly affected the
      prognosis in patients with UTUC managed by RNU. Patient with EUR had a greater
      probability of having higher tumor stages, higher tumor grades, and positive LVI.
      Tumor stage and LVI were independently associated with a worse EUR-free survival.

PMID- 25772385
TI  - Onychomadesis after hand-foot-and-mouth disease outbreak in northern Greece: case
      series and brief review of the literature.
AB  - BACKGROUND: Nail abnormalities in childhood are generally uncommon. Recently,
      onychomadesis was described as a late complication of hand-foot-and-mouth disease
      (HFMD). Onychomadesis outbreaks following HFMD have been reported in many
      countries worldwide. AIM: To present a case series of onychomadesis in children,
      following HFMD outbreak in Northern Greece, and review literature data. METHODS:
      Children with evident onychomadesis attending the outpatient clinic between
      November 2012 and January 2013 were included in the study. A questionnaire
      including demographic personal and family history information of the children was
      completed by the parents. Patients were clinically examined, and their pediatric
      and dermatological records were studied to confirm precedent HFMD. Direct
      microscopic examination and cultures for fungi were performed. Exposure of
      participants to coxsackievirus, based on serology testing during infection, was
      also recorded. RESULTS: Sixty-eight children with onychomadesis were included.
      The mean number of affected nails was 8.82. Fingernails were more often involved.
      Previous clinical diagnosis of HFMD was confirmed in 67/68 cases. The mean time
      from HFMD diagnosis to onychomadesis development was 39.6 days (range: 28-56
      days, STD: 7.33). Direct microscopic examination, as well as cultures for fungal
      species, was negative for the whole sample size. All the nail changes were
      transient with spontaneous regrowth after 1-4 months. CONCLUSION: Our data
      indicate that onychomadesis outbreak in the region of Thessaloniki during fall
      winter 2012-13 was highly related to the outbreak of HFMD. Our study reinforces
      existing evidence for the association between onychomadesis and HFMD.

PMID- 25772386
TI  - New insights in the catalytic mechanism of tyrosine ammonia-lyase given by QM/MM
      and QM cluster models.
AB  - Tyrosine ammonia lyase (TAL) catalyzes the deamination of tyrosine to p-coumaric
      acid in purple phototropic bacteria and Actinomycetales. The enzyme is used in
      bioengineering and has the potential to be used industrially. It belongs to a
      family of enzymes that uses a 4-methylidene-imidazole-5-one (MIO) cofactor to
      catalyze the deamination amino acids. In the present work, we used a QM/MM and a
      QM cluster models of TAL to explore two putative reaction paths for its catalytic
      mechanism. Part of the N-MIO mechanism was previously studied by computational
      methods. We improved on previous studies by using a larger, more complete model
      of the enzyme, and by describing the complete reaction path. The activation
      energy for this mechanism, in agreement with the previous study, is 28.5
      kcal/mol. We also found another reaction path that has overall better kinetics
      and reaches the products in a single reaction step. The barrier for this Single
      Step mechanism is 16.6 kcal/mol, which agrees very well with the experimental
      kcat of 16.0 kcal/mol. The geometrical parameters obtained for the cluster and
      QM/MM models are very similar, despite differences in the relative energies. This
      means that both approaches are capable of describing the correct catalytic path
      of TAL.

PMID- 25772387
TI  - Technical advances in molecular simulation since the 1980s.
AB  - This review describes how the theory and practice of molecular simulation have
      evolved since the beginning of the 1980s when the author started his career in
      this field. The account is of necessity brief and subjective and highlights the
      changes that the author considers have had significant impact on his research and
      mode of working. 

PMID- 25772388
TI  - Characteristics of fibromyalgia independently predict poorer long-term analgesic
      outcomes following total knee and hip arthroplasty.
AB  - OBJECTIVE: While psychosocial factors have been associated with poorer outcomes
      after knee and hip arthroplasty, we hypothesized that augmented pain perception,
      as occurs in conditions such as fibromyalgia, may account for decreased
      responsiveness to primary knee and hip arthroplasty. METHODS: A prospective,
      observational cohort study was conducted. Preoperative phenotyping was conducted
      using validated questionnaires to assess pain, function, depression, anxiety, and
      catastrophizing. Participants also completed the 2011 fibromyalgia survey
      questionnaire, which addresses the widespread body pain and comorbid symptoms
      associated with characteristics of fibromyalgia. RESULTS: Of the 665
      participants, 464 were retained 6 months after surgery. Since individuals who met
      criteria for being classified as having fibromyalgia were expected to respond
      less favorably, all primary analyses excluded these individuals (6% of the
      cohort). In the multivariate linear regression model predicting change in
      knee/hip pain (primary outcome), a higher fibromyalgia survey score was
      independently predictive of less improvement in pain (estimate -0.25, SE 0.044; P
      < 0.00001). Lower baseline joint pain scores and knee (versus hip) arthroplasty
      were also predictive of less improvement (R(2) = 0.58). The same covariates were
      predictive in the multivariate logistic regression model for change in knee/hip
      pain, with a 17.8% increase in the odds of failure to meet the threshold of 50%
      improvement for every 1-point increase in fibromyalgia survey score (P =
      0.00032). The fibromyalgia survey score was also independently predictive of
      change in overall pain and patient global impression of change. CONCLUSION: Our
      findings indicate that the fibromyalgia survey score is a robust predictor of
      poorer arthroplasty outcomes, even among individuals whose score falls well below
      the threshold for the categorical diagnosis of fibromyalgia.

PMID- 25772389
TI  - Recommendations for management of acute pharyngitis in adults.
AB  - Acute pharyngitis in adults is one of the most common infectious diseases seen in
      general practitioners' consultations. Viral aetiology is the most common. Among
      bacterial causes, the main agent is Streptococcus pyogenes or group A beta
      haemolytic streptococcus (GABHS), which causes 5%-30% of the episodes. In the
      diagnostic process, clinical assessment scales can help clinicians to better
      predict suspected bacterial aetiology by selecting patients who should undergo a
      rapid antigen detection test. If these techniques are not performed, an
      overdiagnosis of streptococcal pharyngitis often occurs, resulting in unnecessary
      prescriptions of antibiotics, most of which are broad spectrum. Consequently,
      management algorithms that include the use of predictive clinical rules and rapid
      tests have been set up. The aim of the treatment is speeding up symptom
      resolution, reducing the contagious time span and preventing local suppurative
      and non-suppurative complications. Penicillin and amoxicillin are the antibiotics
      of choice for the treatment of pharyngitis. The association of amoxicillin and
      clavulanate is not indicated as the initial treatment of acute infection. Neither
      are macrolides indicated as first-line therapy; they should be reserved for
      patients allergic to penicillin. The appropriate diagnosis of bacterial
      pharyngitis and proper use of antibiotics based on the scientific evidence
      available are crucial. Using management algorithms can be helpful in identifying
      and screening the cases that do not require antibiotic therapy.

PMID- 25772390
TI  - Prognostic significance of promoter CpG island hypermethylation and repetitive
      DNA hypomethylation in stage I lung adenocarcinoma.
AB  - In carcinogenesis of peripheral pulmonary carcinomas, multiple genetic and
      epigenetic alterations are involved. In this study, we quantified methylation
      levels of repetitive DNA elements (L1 and Alu) and six CpG island methylator
      phenotype (CIMP)-panel markers in various lesions representing steps in the
      development of lung adenocarcinoma (ADC), including atypical adenomatous
      hyperplasia, adenocarcinoma in situ, and invasive ADC. We then assessed
      methylation levels in an independent set of stage I ADCs (n = 100) and correlated
      methylation status with clinicopathological findings and clinical outcome. The
      pattern of changes in the methylation levels of L1 and Alu was different during
      progression of the lesion along the process of multistep carcinogenesis. A
      methylation level of >52.4 % of L1 and of >19.7 % of Alu in stage I ADC was
      associated with shorter cancer-specific survival in univariate but not in
      multivariate analysis. A tumor to normal lung tissue methylation ratio of >0.693
      of L1 was an independent parameter heralding poor prognosis for stage I ADC
      patients. Methylation of CIMP-related genes was found in ADC. Stage I ADC cases
      without methylation of any of the six markers had a significantly shorter cancer
      specific survival than ADC with methylation of one or more markers. The
      combination of tumor to normal L1 methylation ratio > 0.693 and absence of
      methylation of CIMP markers correlated independently with shorter cancer-specific
      survival. In conclusion, our findings suggest that Alu hypomethylation is an
      early and L1 hypomethylation a later event during multistep pulmonary
      carcinogenesis. The prognostic significance of the combination of methylation
      status of L1 and CIMP markers must be validated in large-scale studies of
      pulmonary ADC.

PMID- 25772393
TI  - Improving the tuberculosis drug development pipeline.
AB  - Mycobacterium tuberculosis is considered one of the most successful pathogens and
      multidrug-resistant tuberculosis, a disease that urgently requires new chemical
      entities to be developed for treatment. There are currently several new molecules
      under clinical investigation in the tuberculosis (TB) drug development pipeline.
      However, the complex lifestyle of M. tuberculosis within the host presents a
      barrier to the development of new drugs. In this review, we highlight the reasons
      that make TB drug discovery and development challenging as well as providing
      solutions, future directions and alternative approaches to new therapeutics for
      TB. 

PMID- 25772391
TI  - The Influence of Low Doses of Zearalenone on Distribution of Selected Active
      Substances in Nerve Fibers Within the Circular Muscle Layer of Porcine Ileum.
AB  - The aim of this study was to investigate, whether low doses (25 % of no
      observable adverse effect levels values) of zearalenone (ZEN) can affect the
      expression of active substances in nerve fibers in the muscular layer of porcine
      ileum. The study was performed on ten immature pigs divided into two groups:
      experimental group (n = 5), where zearalenone (10 MUg/kg body weight) was given
      for 42 days, and control animals (n = 5), where placebo was administered.
      Fragments of ileum of all animals were processed for single-labelling
      immunofluorescence technique using the antibodies against vasoactive intestinal
      peptide, neuronal form of nitric oxide synthase, cocaine and amphetamine
      regulatory peptide, galanin, pituitary adenylate cyclase-activating peptide-27
      and substance P. The number of nerve fibers immunoreactive to particular
      substances was evaluated by the counting of nerves per observation field (0.1
      mm(2)). Low doses of zearalenone caused the clear changes in the expression of
      substances studied. The number of nerve fibers immunoreactive to the majority of
      substances increased in experimental animals. The exception was only galanin, the
      expression of which was less after administration of zearalenone. The obtained
      results for the first time show that even low doses of zearalenone can affect the
      nerve fibers in the digestive tract. 

PMID- 25772392
TI  - A novel configuration of a traditional rapid response team decreases non
      intensive care unit arrests and overall hospital mortality.
AB  - BACKGROUND: In-hospital cardiopulmonary arrest (CPA) accounts for substantial
      morbidity and mortality. Rapid response teams (RRTs) are designed to prevent non
      intensive care unit (ICU) CPA through early detection and intervention. However,
      existing evidence has not consistently demonstrated a clear benefit. OBJECTIVE:
      To explore the effectiveness of a novel RRT program design to decrease non-ICU
      CPA and overall hospital mortality. METHODS: This study was conducted from the
      start of fiscal year 2005 to 2011. In November 2007, our hospitals implemented
      RRTs as part of a novel resuscitation program. Charge nurses from each inpatient
      unit underwent training as unit-specific RRT members. Additionally, all inpatient
      staff received annual training in RRT concepts including surveillance and
      recognition of deterioration. We compared the incidence of ICU and non-ICU CPA
      from first complete preimplementation year 2006 to postimplementation years 2007
      to 2011. Overall hospital mortality was also reported. RESULTS: The incidence of
      non-ICU CPA decreased, whereas the incidence of ICU CPA remained unchanged.
      Overall hospital mortality also decreased (2.12% to 1.74%, P < 0.001). The year
      over-year change in RRT activations was inversely related to the change in Code
      Blue activations for each inpatient unit (r = -0.68, P < 0.001). CONCLUSION: Our
      novel RRT program was associated with a decreased incidence of non-ICU CPA and
      improved hospital mortality.

PMID- 25772395
TI  - A multiscale view of therapeutic protein aggregation: a colloid science
      perspective.
AB  - The formation of aggregates in protein-based pharmaceuticals is a major issue
      that can compromise drug safety and drug efficacy. With a view to improving
      protein stability, considerable effort is put forth to unravel the fundamental
      mechanisms underlying the aggregation process. However, therapeutic protein
      aggregation is a complex multistep phenomenon that involves time and length
      scales spanning several orders of magnitude, and strategies addressing protein
      aggregation inhibition are currently still largely empirical in practice. Here,
      we review how key concepts developed in the frame of colloid science can be
      applied to gain knowledge on the kinetics and thermodynamics of therapeutic
      protein aggregation across different length scales. In particular, we discuss the
      use of coarse-grained molecular interaction potentials to quantify protein
      colloidal stability. We then show how population balance equations simulations
      can provide insights into the mechanisms of aggregate formation at the mesoscale,
      and we highlight the strength of the concept of fractal scaling to quantify
      irregular aggregate morphologies. Finally, we correlate the macroscopic
      rheological properties of protein solutions with the occupied volume fraction and
      the aggregate structure. Overall, this work illustrates the power and limitations
      of colloidal approaches in the multiscale description of the aggregation of
      therapeutic proteins. 

PMID- 25772398
TI  - The challenges of treating women with recurrent urinary tract infections in
      primary care: a qualitative study of GPs' experiences of conventional management
      and their attitudes towards possible herbal options.
AB  - AIM: To explore GPs' experiences of managing recurrent urinary tract infections
      (RUTIs) and their views on the use of herbal medicines for this condition.
      BACKGROUND: RUTIs are an important problem commonly managed in primary care.
      Antibiotic prophylaxis is an effective treatment for acute infections but growing
      microbial resistance, adverse effects, and the lack of sustained long-term
      benefits mean that novel treatments are required. There are a number of promising
      reports of herbal medicines being used to treat RUTIs. METHODS: A total of 15 GPs
      (seven female; aged 34-59 years; in practice from 3 to 31 years) were purposively
      sampled and took part in semi-structured face-to-face and telephone interviews.
      Interviews were digitally recorded, transcribed, and analysed using inductive
      thematic analysis. Data collection and analysis proceeded iteratively to allow
      emerging themes to inform subsequent interviews. FINDINGS: Participants were
      aware of the disabling effect of RUTIs on women's lives. GPs experienced
      significant challenges in their management of RUTIs with decisions about the
      provision of antibiotics being particularly complex. While some participants were
      open to the possibility of herbal treatment options they required more research
      into effectiveness and safety, better regulation of herbal practitioners, and
      assurance about herbal quality control and potential herb-drug interactions.

PMID- 25772399
TI  - Introducing the Concept of the Minimally Important Difference to Determine a
      Clinically Relevant Change on Patient-Reported Outcome Measures in Patients with
      Intermittent Claudication.
AB  - PURPOSE: The minimally important difference (MID) represents the smallest change
      in score on patient-reported outcome measures that is relevant to patients. The
      aim of this study was to introduce the MID for the Vascular Quality of Life
      Questionnaire (VascuQol) and the walking impairment questionnaire (WIQ) for
      patients with intermittent claudication (IC). METHODS: In this multicenter study,
      we recruited 294 patients with IC between July and October 2012. Patients
      completed the VascuQol, with scores ranging from 1 to 7 (worst to best), and the
      WIQ, with scores ranging from 0 to 1 (worst to best) at first visit and after 4
      months follow-up. In addition, patients answered an anchor-question rating their
      health status compared to baseline, as being improved, unchanged, or
      deteriorated. The MID for improvement and deterioration was calculated by an
      anchor-based approach, and determined with the upper and lower limits of the 95 %
      confidence interval of the mean change of the group who had not changed according
      to the anchor-question. RESULTS: For the MID analyses of the VascuQol and WIQ,
      163 and 134 patients were included, respectively. The MID values for the VascuQol
      (mean baseline score 4.25) were 0.87 for improvement and 0.23 for deterioration.
      For the WIQ (mean baseline score 0.39), we found MID values of 0.11 and -0.03 for
      improvement and deterioration, respectively. CONCLUSION: In this study, we
      calculated the MID for the VascuQol and the WIQ. Applying these MID facilitates
      better interpretation of treatment outcomes and can help to set treatment goals
      for individual care.

PMID- 25772400
TI  - Iliocaval Confluence Stenting for Chronic Venous Obstructions.
AB  - PURPOSE: Different techniques have been described for stenting of venous
      obstructions. We report our experience with two different confluence stenting
      techniques to treat chronic bi-iliocaval obstructions. MATERIALS AND METHODS:
      Between 11/2009 and 08/2014 we treated 40 patients for chronic total bi-iliocaval
      obstructions. Pre-operative magnetic resonance venography showed bilateral
      extensive post-thrombotic scarring in common and external iliac veins as well as
      obstruction of the inferior vena cava (IVC). Stenting of the IVC was performed
      with large self-expandable stents down to the level of the iliocaval confluence.
      To bridge the confluence, either self-expandable stents were placed inside the
      IVC stent (24 patients, SECS group) or high radial force balloon-expandable
      stents were placed at the same level (16 patients, BECS group). In both cases,
      bilateral iliac extensions were performed using nitinol stents. RESULTS:
      Recanalization was achieved for all patients. In 15 (38 %) patients, a hybrid
      procedure with endophlebectomy and arteriovenous fistula creation needed to be
      performed because of significant involvement of inflow vessels below the inguinal
      ligament. Mean follow-up was 443 +/- 438 days (range 7-1683 days). For all
      patients, primary, assisted-primary, and secondary patency rate at 36 months were
      70, 73, and 78 %, respectively. Twelve-month patency rates in the SECS group were
      85, 85, and 95 % for primary, assisted-primary, and secondary patency. In the
      BECS group, primary patency was 100 % during a mean follow-up period of 134 +/-
      118 (range 29-337) days. CONCLUSION: Stenting of chronic bi-iliocaval obstruction
      shows relatively high patency rates at medium follow-up. Short-term patency seems
      to favor confluence stenting with balloon-expandable stents.

PMID- 25772401
TI  - Impact on Patient Safety and Satisfaction of Implementation of an Outpatient
      Clinic in Interventional Radiology (IPSIPOLI-Study): A Quasi-Experimental
      Prospective Study.
AB  - PURPOSE: Interventional radiology (IR) procedures are associated with high rates
      of preparation and planning errors. In many centers, pre-procedural consultation
      and screening of patients is performed by referring physicians. Interventional
      radiologists have better knowledge about procedure details and risks, but often
      only get acquainted with the patient in the procedure room. We hypothesized that
      patient safety (PS) and patient satisfaction (PSAT) in elective IR procedures
      would improve by implementation of a pre-procedural visit to an outpatient IR
      clinic. MATERIAL AND METHODS: IRB approval was obtained and informed consent was
      waived. PS and PSAT were measured in patients undergoing elective IR procedures
      before (control group; n = 110) and after (experimental group; n = 110)
      implementation of an outpatient IR clinic. PS was measured as the number of
      process deviations. PSAT was assessed using a questionnaire measuring Likert
      scores of three dimensions: interpersonal care aspects,
      information/communication, and patient participation. Differences in PS and PSAT
      between the two groups were compared using an independent t test. RESULTS: The
      average number of process deviations per patient was 0.39 in the control group
      compared to 0.06 in the experimental group (p < 0.001). In 9.1 % patients in the
      control group, no legal informed consent was obtained compared to 0 % in the
      experimental group. The mean overall Likert score was significantly higher in the
      experimental group compared to the control group: 2.68 (SD 0.314) versus 2.48 (SD
      0.381) (p < 0.001). CONCLUSION: PS and PSAT improve significantly if patients
      receive consultation and screening in an IR outpatient clinic prior to elective
      IR procedures.

PMID- 25772402
TI  - Patient Compliance with Surveillance Following Elective Endovascular Aneurysm
      Repair.
AB  - PURPOSE: Integral to maintaining good outcomes post-endovascular aneurysm repair
      (EVAR) is a robust surveillance protocol. A significant proportion of patients
      fail to comply with surveillance, exposing themselves to complications. We
      examine EVAR surveillance in Wessex (UK), exploring factors that may predict poor
      compliance. METHODS: Retrospective analysis of 179 consecutive elective EVAR
      cases [2008-2013] was performed. 167 patients were male, with the age range of 50
      95. Surveillance was conducted centrally (tertiary referral trauma centre) and at
      four spoke units. Surveillance compliance and predictors of non-compliance
      including age, gender, co-morbid status, residential location and socioeconomic
      status were analysed for univariate significance. RESULTS: Fifty patients (27.9
      %) were non-compliant with surveillance; 14 (8.1 %) had no imaging post-EVAR. At
      1 year, 56.1 % (of 123 patients) were compliant. At years 2 and 3, 41.5 and 41.2
      % (of 65 and 34 patients, respectively) were compliant. Four years post-EVAR,
      only one of eight attended surveillance (12.5 %). There were no statistically
      significant differences in age (p = 0.77), co-morbid status or gender (p = 0.64).
      Distance to central unit (p = 0.67) and surveillance site (p = 0.56) was non
      significant. While there was a trend towards compliance in upper-middle-class
      socioeconomic groups (ABC1 vs. C1C2D), correlating with >50 % of non-compliant
      patients living within <10 mile radius of the central unit, overall predictive
      value was not significant (p = 0.82). CONCLUSIONS: Compliance with surveillance
      post-EVAR is poor. No independent predictor of non-compliance has been confirmed,
      but socioeconomic status appears to be relevant. There is a worrying drop-off in
      attendance beyond the first year. This study highlights a problem that needs to
      be addressed urgently, if we are to maintain good outcomes post-EVAR.

PMID- 25772403
TI  - Evidence for phosphorus bonding in phosphorus trichloride-methanol adduct: a
      matrix isolation infrared and ab initio computational study.
AB  - The weak interaction between PCl3 and CH3OH was investigated using matrix
      isolation infrared spectroscopy and ab initio computations. In a nitrogen matrix
      at low temperature, the noncovalent adduct was generated and characterized using
      Fourier transform infrared spectroscopy. Computations were performed at B3LYP/6
      311++G(d,p), B3LYP/aug-cc-pVDZ, and MP2/6-311++G(d,p) levels of theory to
      optimize the possible geometries of PCl3-CH3OH adducts. Computations revealed two
      minima on the potential energy surface, of which, the global minimum is
      stabilized by a noncovalent P...O interaction, known as a pnictogen bonding
      (phosphorus bonding or P-bonding). The local minimum corresponded to a cyclic
      adduct, stabilized by the conventional hydrogen bonding (Cl...H-O and Cl...H-C
      interactions). Experimentally, 1:1 P-bonded PCl3-CH3OH adduct in nitrogen matrix
      was identified, where shifts in the P-Cl modes of PCl3, O-C, and O-H modes of
      CH3OH submolecules were observed. The observed vibrational frequencies of the P
      bonded adduct in a nitrogen matrix agreed well with the computed frequencies.
      Furthermore, computations also predicted that the P-bonded adduct is stronger
      than H-bonded adduct by ~1.56 kcal/mol. Atoms in molecules and natural bond
      orbital analyses were performed to understand the nature of interactions and
      effect of charge transfer interaction on the stability of the adducts. 

PMID- 25772404
TI  - Multiple malignant changes and recurrent infections in the skin associated with
      long-term exposure to ultraviolet light and topical psoralen plus ultraviolet A
      therapy.

PMID- 25772405
TI  - Characterization of novel microsatellite markers for Hyphantria cunea and
      implications for other Lepidoptera.
AB  - This is the first report of microsatellite markers (simple sequence repeats, SSR)
      for fall webworm, Hyphantria cunea (Drury) (Lepidoptera: Arctiidae), an important
      quarantine pest in some European and Asian countries. Here, we developed 48
      microsatellite markers for H. cunea from SSR enrichment libraries. Sequences
      isolated from libraries were sorted into four categories and analyzed. Our
      results suggest that sequences classified as Grouped should not be used for
      microsatellite primer design. The genetic diversity of microsatellite loci was
      assessed in 72 individuals from three populations. The number of alleles per
      locus ranged from 2 to 5 with an average of 3. The observed and expected
      heterozygosities of loci ranged from 0 to 0.958 and 0 to 0.773, respectively. A
      total of 18 out of 153 locus/population combinations deviated significantly from
      Hardy-Weinberg equilibrium. Moreover, significant linkage disequilibrium was
      detected in one pair of loci (1275 pairs in total). In the neutral test, two loci
      were grouped into the candidate category for positive selection and the remainder
      into the neutral category. In addition, a complex mutation pattern was observed
      for these loci, and F ST performed better than did R ST for the estimation of
      population differentiation in different mutation patterns. The results of the
      present study can be used for population genetic studies of H. cunea. 

PMID- 25772406
TI  - Correspondence: fecal calprotectin and cut-off levels in inflammatory bowel
      disease.

PMID- 25772407
TI  - The Cardiovascular Consequences of Excess Sitting Time.

PMID- 25772408
TI  - RZZ and Mad1 dynamics in Drosophila mitosis.
AB  - The presence or absence of Mad1 at kinetochores is a major determinant of spindle
      assembly checkpoint (SAC) activity, the surveillance mechanism that delays
      anaphase onset if one or more kinetochores remain unattached to spindle fibers.
      Among the factors regulating the levels of Mad1 at kinetochores is the Rod, Zw10,
      and Zwilch (RZZ) complex, which is required for Mad1 recruitment through a
      mechanism that remains unknown. The relative dynamics and interactions of Mad1
      and RZZ at kinetochores have not been extensively investigated, although Mad1 has
      been reported to be stably recruited to unattached kinetochores. In this study,
      we directly compare Mad1-green fluorescent protein (GFP) turnover dynamics on
      unattached Drosophila kinetochores with that of RZZ, tagged either with GFP-Rod
      or GFP-Zw10. We find that nearly 40 % of kinetochore-bound Mad1 has a significant
      dynamic component, turning over with a half-life of 12 s. RZZ in contrast is
      essentially stable on unattached kinetochores. In addition, we report that a
      fraction of RZZ and Mad1 can co-immunoprecipitate, indicating that the
      genetically determined recruitment hierarchy (in which Mad1 depends on RZZ) may
      reflect a physical association of the two complexes. 

PMID- 25772409
TI  - Nuclear receptors in vascular biology.
AB  - Nuclear receptors sense a wide range of steroids and hormones (estrogens,
      progesterone, androgens, glucocorticoid, and mineralocorticoid), vitamins (A and
      D), lipid metabolites, carbohydrates, and xenobiotics. In response to these
      diverse but critically important mediators, nuclear receptors regulate the
      homeostatic control of lipids, carbohydrate, cholesterol, and xenobiotic drug
      metabolism, inflammation, cell differentiation and development, including
      vascular development. The nuclear receptor family is one of the most important
      groups of signaling molecules in the body and as such represent some of the most
      important established and emerging clinical and therapeutic targets. This review
      will highlight some of the recent trends in nuclear receptor biology related to
      vascular biology. 

PMID- 25772410
TI  - Acute hearing loss in patients with hematological disorders.
AB  - OBJECTIVE: This study adopted an inner ear test battery to investigate the causes
      of acute sensorineural hearing loss in patients with hematological disorders.
      METHODS: During the past 20 years, the authors have experienced 14 patients with
      hematological disorders, i.e. leukemia or aplastic anemia, having acute
      sensorineural hearing loss. An inner ear test battery comprising audiometry and
      cervical vestibular-evoked myogenic potential (cVEMP), ocular VEMP (oVEMP), and
      caloric tests was performed. RESULTS: Diagnoses comprised of sudden sensorineural
      hearing loss in 12 patients and endolymphatic hydrops in four patients (two
      patients had one ear with sudden sensorineural hearing loss while the other ear
      had endolymphatic hydrops). Percentages of recruitment phenomenon showed a
      significant difference between endolymphatic hydrops and sudden sensorineural
      hearing loss. Abnormal percentages for mean hearing level (86%), cVEMP test
      (71%), oVEMP test (25%), and caloric test (14%) exhibited a significant
      sequential decline in these patients. CONCLUSION: Acute sensorineural hearing
      loss in a patient with leukemia or aplastic anemia may be related to either
      sudden sensorineural hearing loss or endolymphatic hydrops. A significant
      sequential decline in the function of the cochlea, saccule, utricle, and
      semicircular canals indicates that the pars inferior is more vulnerable to blood
      insult than the pars superior.

PMID- 25772411
TI  - Is type 2 diabetes related to leukoaraiosis? an updated review.
AB  - A significantly increased interest has been dedicated to the study of the effects
      of diabetes mellitus (DM) on the brain. DM is associated with an increased risk
      of stroke and cognitive decline. In patients with DM, neuroimaging discloses with
      high-frequency structural changes, such as cerebral atrophy, infarcts and white
      matter lesions, also called leukoaraiosis (LA), an expression of small vessel
      disease. A previous review showed a relation between DM and both cerebral atrophy
      and lacunar infarcts, while the question about the relation between DM and LA
      remained unanswered. In this review, we provide an update on data on this last
      association. In the reviewed studies, we examined the presence of DM, other
      disease characteristics, such as duration and complications, and laboratory
      markers of the disease such as blood glycated hemoglobin (HbA1c), insulin
      resistance, insulin concentrations and their association with LA. About 40% of
      the reviewed studies reported a statistically significant association between DM
      and LA. Long-standing DM and a poor glycemic control were associated with severe
      LA. Studies using innovative MRI techniques, such as diffusion tensor imaging
      (DTI), reported a significant association between microstructural white matter
      alterations and DM. This review highlights more firmly than previously reported
      the existence of a relation between DM and both presence and severity of LA.
      These results are possibly due to more sensitive and advanced imaging techniques
      recently used to study the extent of LA. However, because of the heterogeneous
      methodology used in the reviewed studies, a definitive conclusion cannot be
      drawn. 

PMID- 25772412
TI  - Psychological Transformation by an Intervention to Facilitate Benefit Finding
      Among People With Chronic Mental Illness in Japan.
AB  - PURPOSE: This study aimed to preliminarily explore the psychological
      transformation effected by a newly developed intervention program for
      facilitating benefit finding among individuals with chronic mental illness in
      Japan. DESIGN AND METHODS: An intervention study with three weekly group sessions
      was implemented, and qualitative data on the participants' experience of benefit
      finding were obtained by a questionnaire survey and analyzed using content
      analysis technique. FINDINGS: Of the 31 participants, 23 responded that they
      realized some sort of benefit finding through the intervention. PRACTICE
      IMPLICATIONS: The program component in question may contribute to enhanced
      benefit finding for people with chronic mental illness while longitudinal studies
      involving more participants are desirable.

PMID- 25772413
TI  - Influence of salt type and ionic strength on self-assembly of dextran sulfate
      ciprofloxacin nanoplexes.
AB  - We evaluated an analytical setup to identify optimal preparation conditions for
      nanoplex formation of small molecule drugs and polyelectrolytes using
      ciprofloxacin (CIP) and dextran sulfate (DS) as model compounds. The suitability
      of isothermal titration calorimetry (ITC) as a screening tool for rational
      formulation optimization was assessed. Besides ITC, static and dynamic light
      scattering, zeta potential measurements and scanning electron microscopy were
      applied to analyze the influence of different salt types and ionic strengths on
      CIP/DS nanoplex formation. The addition of low amounts of salt, especially 0.1M
      NaCl, improved the formation of CIP/DS nanoplexes. The presence of low amounts of
      salt led to smaller and more numerous particles of higher uniformity but had no
      influence on the release of CIP from nanoplexes. Furthermore, the molar range,
      within which efficient complexation was achieved, was broader in the presence of
      0.1M NaCl than in the absence of salt with overall comparable complexation
      efficiency. Importantly, binding affinity correlated with particle shape and
      morphology, potentially enabling optimization of critical quality attributes
      based on ITC data. Altogether, ITC along with supplemental methods is a versatile
      screening tool for the evaluation of nanoplex formulation conditions regarding
      mixing ratio, salt type and ionic strength. 

PMID- 25772414
TI  - Improvement of the antibacterial activity of daptomycin-loaded polymeric
      microparticles by Eudragit RL 100: an assessment by isothermal microcalorimetry.
AB  - The aim of the present study was to develop novel daptomycin-loaded acrylic
      microparticles with improved release profiles and antibacterial activity against
      two clinically relevant methicillin-susceptible and methicillin-resistant
      Staphylococcus aureus strains (MSSA and MRSA, respectively). Daptomycin was
      encapsulated into poly(methyl methacrylate) (PMMA) and PMMA-Eudragit RL 100 (EUD)
      microparticles by a double emulsion-solvent evaporation method. For comparison
      purposes similar formulations were prepared with vancomycin. Particle morphology,
      size distribution, encapsulation efficiency, surface charge, physicochemical
      properties, in vitro release and biocompatibility were assessed. Particles
      exhibited a micrometer size and a spherical morphology. The addition of EUD to
      the formulation caused a shift in the surface charge of the particles from
      negative zeta potential values (100% PMMA formulations) to strongly positive. It
      also improved daptomycin encapsulation efficiency and release, whereas vancomycin
      encapsulation and release were strongly hindered. Plain and antibiotic-loaded
      particles presented comparable biocompatibility profiles. The antibacterial
      activity of the particles was assessed by isothermal microcalorimetry against
      both MSSA and MRSA. Daptomycin-loaded PMMA-EUD particles presented the highest
      antibacterial activity against both strains. The addition of 30% EUD to the
      daptomycin-loaded PMMA particles caused a 40- and 20-fold decrease in the minimum
      inhibitory (MIC) and bactericidal concentration (MBC) values, respectively, when
      compared to the 100% PMMA formulations. On the other hand, vancomycin-loaded
      microparticles presented the highest antibacterial activity in PMMA particles.
      Unlike conventional methods, isothermal microcalorimetry proved to be a real
      time, sensitive and accurate method for assessment of antibacterial activity of
      antibiotic-loaded polymeric microparticles. Finally, the addition of EUD to
      formulations proved to be a powerful strategy to improve daptomycin encapsulation
      efficiency and release, and consequently improving the microparticles activity
      against two relevant S. aureus strains.

PMID- 25772415
TI  - Triboelectrification and dissolution property enhancements of solid dispersions.
AB  - The use of solid dispersion techniques to modify physicochemical properties and
      improve solubility and dissolution rate may result in alteration to electrostatic
      properties of particles. Particle triboelectrification plays an important part in
      powder processing, affecting end product quality due to particle deposition and
      powder loss. This study investigates the use of glucosamine hydrochloride (GLU)
      in solid dispersions with indomethacin. Solvents selected for the preparation of
      the dispersions were acetone, acetone-water, ethanol and ethanol-water. Solid
      state characterizations (DSC, FTIR and XRPD) and dissolution were conducted.
      Dispersions were subjected to charge using a custom built device based on a
      shaking concept, consisting of a Faraday cup connected to an electrometer. All
      dispersions improved the dissolution rate of indomethacin. Analysis showed the
      method of preparation of the dispersion induced polymorphic forms of the drug.
      Indomethacin had a high propensity for charging (-411 nC/g). GLU had a very low
      charge (-1 nC/g). All dispersions had low charges (-1 to 14 nC/g). Acetone as a
      solvent, or in combination with water, produced samples with an electronegative
      charge in polarity. The same approach with ethanol produced electropositive
      charging. The results show the selection of solvents can influence powder charge
      thereby improving powder handling as well as dissolution properties.

PMID- 25772416
TI  - Development and validation of an in vitro release method for topical particulate
      delivery systems.
AB  - The aim of this study was to develop an in vitro release method for topical
      particulate delivery systems using the immersion cell in combination with paddle
      dissolution apparatus. Chitosan- and methacrylate-based microparticles with
      mupirocin were prepared and used as model topical delivery systems for method
      development. Diffusion of the drug occurred across a mixed cellulose ester
      membrane, which demonstrated low drug adsorption and low diffusional resistance.
      After an initial lag phase the amount of drug released became proportional to the
      square root of time. The method was discriminative toward differences in
      formulation, as well as toward differences in drug concentration inside the
      sample compartment. The method was further used to confirm sameness between
      batches of the same composition prepared by the same process. Variations in
      paddle rotation speed (25 rpm, 50 rpm, 100 rpm), paddle height (1cm, 2.5 cm) and
      volume of release medium (100ml, 200 ml) did not significantly alter the release
      rates. The method of analysis was validated according to ICH guidelines.
      Currently there are no compendial or standard methods and apparatuses for in
      vitro release testing of topical microparticles. The developed method can be a
      useful guide in formulation development of such delivery systems.

PMID- 25772417
TI  - Cationic peptides as RNA compaction agents: a study on the polyA compaction
      activity of a linear alpha,epsilon-oligo-L-lysine.
AB  - In this work, we investigate the compaction activity of a sequential
      alpha,epsilon-peptide composed of l-lysines towards two RNA targets, in view of
      its possible pharmaceutical application in RNA-targeting and RNA delivery. The
      basic oligolysine, object of the present study, proved not only to be efficient
      in compacting the single-stranded polyA RNA, but also to strongly interact with
      the polyA.polyU complex, as evidenced by CD-binding and UV-melting experiments.
      In particular, the marked differences in the CD spectra of the RNA targets upon
      addition of the peptide, as well as the different UV melting behaviour for the
      polyA.polyU complex in the presence and absence of the peptide, sustain the
      hypothesis of a strong RNA compaction capacity of the alpha,epsilon-oligolysine.
      Finally, by using HPLC analysis, we found a good resistance of the peptide
      against the lytic action of human serum, an important requirement in view of in
      vitro/in vivo biological assays.

PMID- 25772418
TI  - Fine powder flow under humid environmental conditions from the perspective of
      surface energy.
AB  - The influence of humidity on surface energetics and flow behavior of fine
      pharmaceutical powders was investigated. Amorphous and crystalline fine powders
      with hydrophilic (Corn starch and Avicel PH105) and hydrophobic (ibuprofen)
      nature were considered for this study. The surface energy was determined using
      surface energy analyzer and flow behavior was measured in terms of unconfined
      yield stress (UYS) using a shear tester. The study showed that unlike hydrophobic
      ibuprofen powder, surface energy and flow of hydrophilic excipient powders were
      affected by relative humidity (RH). The Lifshitz-van der Waals dispersive
      (gamma(LW)) component of surface energy barely changed with varying RH for all
      pharmaceutical powders. For hydrophilic excipients, the specific component of
      surface energy (gamma(SP)) was found to increase with increasing RH. Furthermore,
      for these excipients, flow deterioration at elevated RH was observed due to
      increased capillary bridge formation. Detailed analysis showed that gamma(SP)
      component of surface energy can be an effective indicator for flow behavior of
      fine powders under varying humid conditions. The present study also brought out
      the existence of different regimes of probable interparticle forces which dictate
      the bulk flow behavior of fine hydrophilic powder under humid conditions.

PMID- 25772419
TI  - Inkjet printing for pharmaceutics - A review of research and manufacturing.
AB  - Global regulatory, manufacturing and consumer trends are driving a need for
      change in current pharmaceutical sector business models, with a specific focus on
      the inherently expensive research costs, high-risk capital-intensive scale-up and
      the traditional centralised batch manufacturing paradigm. New technologies, such
      as inkjet printing, are being explored to radically transform pharmaceutical
      production processing and the end-to-end supply chain. This review provides a
      brief summary of inkjet printing technologies and their current applications in
      manufacturing before examining the business context driving the exploration of
      inkjet printing in the pharmaceutical sector. We then examine the trends reported
      in the literature for pharmaceutical printing, followed by the scientific
      considerations and challenges facing the adoption of this technology. We
      demonstrate that research activities are highly diverse, targeting a broad range
      of pharmaceutical types and printing systems. To mitigate this complexity we show
      that by categorising findings in terms of targeted business models and Active
      Pharmaceutical Ingredient (API) chemistry we have a more coherent approach to
      comparing research findings and can drive efficient translation of a chosen drug
      to inkjet manufacturing. 

PMID- 25772420
TI  - Characterization of naproxen-loaded solid SMEDDSs prepared by spray drying: the
      effect of the polysaccharide carrier and naproxen concentration.
AB  - The purpose of this study was to prepare solid SMEDDS (sSMEDDS) particles
      produced by spray-drying using maltodextrin (MD), hypromellose (HPMC), and a
      combination of the two as a solid carrier. Naproxen (NPX) as the model drug was
      dissolved (at 6% concentration) or partially suspended (at 18% concentration) in
      a liquid SMEDDS composed of Miglyol((r)) 812, PeceolTM, Gelucire((r)) 44/14, and
      Solutol((r)) HS 15. Among the sSMEDDSs tested, the MD-based sSMEDDSs (with a
      granular, smooth-surfaced, microspherical appearance) preserved the self
      microemulsifying properties of liquid SMEDDSs and exhibited dissolution profiles
      similar to those of liquid SMEDDSs, irrespective of the concentration of NPX. In
      contrast, HPMC-based sSMEDDSs (irregular-shaped microparticles) exhibited
      slightly prolonged release times due to the polymeric nature of the carrier.
      Differential scanning calorimetry (DSC), X-ray powder diffraction (XRPD), and
      Raman mapping analysis confirmed molecularly dissolved NPX (at 6% of drug
      loading), whereas at 18% NPX loading drug is partially molecularly dissolved and
      partially in the crystalline state.

PMID- 25772421
TI  - Lecithin/TPGS-based spray-dried self-microemulsifying drug delivery systems: In
      vitro pulmonary deposition and cytotoxicity.
AB  - The aim of the present work was to develop a new solid self-microemulsifying drug
      delivery system (SMEDDS) for the pulmonary delivery of the poorly water-soluble
      anti-cancer drug atorvastatin (AVT). Microemulsion (ME) was first developed using
      isopropyl myristate (IPM), a combination of 2 biocompatible surfactants:
      lecithin/d-alpha-tocopheryl polyethylene glycol succinate (TPGS) and ethanol as
      co-surfactant. Two types of lecithin with different phosphatidylcholine (PC)
      contents were compared. Phase diagram, physico-chemical characterization and
      stability studies were used to investigate ME region. Solid SMEDDS were then
      prepared by spray-drying the selected ME using a combination of carriers composed
      of sugars, leucine as dispersibility enhancer with or without polyethylene glycol
      (PEG) 6000. Yield, flow properties, particle size and in vitro pulmonary
      deposition were used to characterize the spray-dried powders. Reconstituted MEs
      were characterized in terms of morphology, particle size and size distribution.
      In vitro cytotoxicity study was undertaken on lung cancer cell line for the
      selected MEs and SD-SMEDDS formulae. Results showed that the most satisfactory
      MEs properties were obtained with 1:3 lecithin/TPGS, 1:1 lecithin/oil and 1:1
      surfactant/co-surfactant ratios. A larger ME area was obtained with lecithin
      containing 100% PC compared to the less expensive lecithin containing 20% PC. By
      manipulating spray drying parameters, carrier composition and ratio of ME lipids
      to carrier, microparticles with more than 70% of respirable fraction could be
      prepared. The ME was efficiently recovered in simulated lung fluid even after
      removal of alcohol. The concurrent delivery of AVT with TPGS in solid SMEDDS
      greatly enhanced the cytotoxic activity on lung cancer cells.

PMID- 25772422
TI  - Multiple modes of assessment of gait are better than one to predict incident
      falls.
AB  - BACKGROUND: Though gait evaluation is recommended as a core component of fall
      risk assessments, a systematic examination of the predictive validity of
      different modes of gait assessments for falls is lacking. OBJECTIVE: To compare
      three commonly employed gait assessments - self-reported walking difficulties,
      clinical evaluation, and quantitative gait - to predict incident falls. MATERIALS
      AND METHODS: 380 community-dwelling older adults (mean age 76.5 +/- 6.8 y, 55.8%
      female) were evaluated with three independent gait assessment modes: patient
      centered, quantitative, and clinician-diagnosed. The association of these three
      gait assessment modes with incident falls was examined using Cox proportional
      hazards models. RESULTS: 23.2% of participants self-reported walking
      difficulties, 15.5% had slow gait, and 48.4% clinical gait abnormalities. 30.3%
      had abnormalities on only one assessment, whereas only 6.3% had abnormalities on
      all three. Over a mean follow-up of 24.2 months, 137 participants (36.1%) fell.
      Those with at least two abnormal gait assessments presented an increased risk of
      incident falls (hazard ratio (HR): 1.61, 95% confidence interval (CI): 1.04-2.49)
      in comparison to the 169 participants without any abnormalities on any of the
      three assessments. CONCLUSIONS: Multiple modes of gait evaluation provide a more
      comprehensive mobility assessment than only one assessment alone, and better
      identify incident falls in older adults.

PMID- 25772423
TI  - Acute toxicity profile of tolperisone in overdose: Observational poison centre
      based study.
AB  - INTRODUCTION: Tolperisone is a centrally acting muscle relaxant that acts by
      blocking voltage-gated sodium and calcium channels. There is a lack of
      information on the clinical features of tolperisone poisoning in the literature.
      The aim of this study was to investigate the demographics, circumstances and
      clinical features of acute overdoses with tolperisone. METHODS: An observational
      study of acute overdoses of tolperisone, either alone or in combination with one
      non-steroidal anti-inflammatory drug in a dose range not expected to cause
      central nervous system effects, in adults and children (< 16 years), reported to
      our poison centre between 1995 and 2013. RESULTS: 75 cases were included: 51
      females (68%) and 24 males (32%); 45 adults (60%) and 30 children (40%). Six
      adults (13%) and 17 children (57%) remained asymptomatic, and mild symptoms were
      seen in 25 adults (56%) and 10 children (33%). There were nine adults (20%) with
      moderate symptoms, and five adults (11%) and three children (10%) with severe
      symptoms. Signs and symptoms predominantly involved the central nervous system:
      somnolence, coma, seizures and agitation. Furthermore, some severe cardiovascular
      and respiratory signs and symptoms were reported. The minimal dose for seizures
      and severe symptoms in adults was 1500 mg. In 11 cases the latency between the
      ingestion and the onset of symptoms was known and was reported to be 0.5-1.5 h.
      CONCLUSIONS: The acute overdose of tolperisone may be life-threatening, with a
      rapid onset of severe neurological, respiratory and cardiovascular symptoms. With
      alternative muscle relaxants available, indications for tolperisone should be
      rigorously evaluated.

PMID- 25772424
TI  - Histopathological indices in sole (Solea solea) and hake (Merluccius merluccius)
      for implementation of the European Marine Strategy Framework Directive along the
      Basque continental shelf (SE Bay of Biscay).
AB  - Sole and hake, together with sediments, were collected during two campaigns along
      the Basque continental shelf to study the utility of two existing
      histopathological indices for assessing the biological effects of contaminants to
      implement the European Marine Strategy Framework Directive. Hepatic and gonadal
      histopathology were measured, and metal and/or organic contaminants were
      determined in both liver and sediments. Sediments from the Basque continental
      shelf were found to be moderately impacted by metals but non-impacted by organic
      compounds. Metal bioaccumulation and histopathological lesions in liver were
      higher in sole than in hake, although non-specific and early non-neoplastic
      toxicopathic lesions were observed in both species. No gross alterations were
      recorded in gonad. The two histopathological indices applied were highly
      correlated in both organs but the lack of correlation between sediment
      contamination levels, bioaccumulation and histopathological indices suggests that
      other factors, rather than pollution alone, are responsible for the biological
      effects observed. 

PMID- 25772425
TI  - Peer Victimization and Anxiety in Genetically Vulnerable Youth: The Protective
      Roles of Teachers' Self-Efficacy and Anti-Bullying Classroom Rules.
AB  - Many victimized youngsters are at risk of developing internalizing problems, and
      this risk seems to be especially pronounced when they are genetically vulnerable
      for these problems. It is unclear, however, whether protective features of the
      school environment such as anti-bullying classroom policies and teacher's
      perceived self-efficacy in handling bullying situations can mitigate these
      negative outcomes. Using a genetically informed design based on twins, this study
      examined the potential moderating role of classroom anti-bullying policies and
      teachers' perceived self-efficacy in handling bullying situations in regard to
      the additive and interactive effects of peer victimization and genetic
      vulnerability on anxiety symptoms. To this end, 208 monozygotic and same-sex
      dizygotic twins (120 girls) rated their level of anxiety and peer victimization
      in grade 6 (mean age = 12.1 years, SD = 2.8). Teachers rated their self-efficacy
      in handling bullying situations and the extent of anti-bullying classroom
      policies. Multilevel regressions revealed triple interactions showing that
      genetic disposition for anxiety predicted actual anxiety for twins who were
      highly victimized by their peers, but only when their teachers had low perceived
      self-efficacy in handling bullying situations or when anti-bullying classroom
      rules were absent or rarely enforced. In contrast, for victimized youth with
      teachers who perceive themselves as effective or in classrooms where anti
      bullying classroom policies were strongly enforced, genetic disposition for
      anxiety was not associated with actual anxiety symptoms. Anti-bullying programs
      should continue to promote teachers' involvement, as well as the enforcement of
      anti-bullying classroom policies, in order to diminish peer victimization and its
      related consequences.

PMID- 25772426
TI  - Late-Emerging and Resolving Dyslexia: A Follow-Up Study from Age 3 to 14.
AB  - This study focuses on the stability of dyslexia status from Grade 2 to Grade 8 in
      four groups: (a) no dyslexia in either grade (no-dyslexia, n = 127); (b) no
      dyslexia in Grade 2 but dyslexia in Grade 8 (late-emerging, n = 18); (c) dyslexia
      in Grade 2 but not in Grade 8 (resolving, n = 15); and (d) dyslexia in both
      grades (persistent-dyslexia, n = 22). We examined group differences from age 3.5
      to age 14 in (a) reading, vocabulary, phonology, letter knowledge, rapid naming,
      IQ, verbal memory; (b) familial and environmental risk and supportive factors;
      and (c) parental skills in reading, phonology, rapid naming, verbal memory, and
      vocabulary. Our findings showed group differences both in reading and cognitive
      skills of children as well as their parents. Parental education, book-reading
      frequency, and children's IQ, however, did not differentiate the groups. The
      children in the persistent-dyslexia group exhibited widespread language and
      cognitive deficits across development. Those in the resolving group had problems
      in language and cognitive skills only prior to school entry. In the late-emerging
      group, children showed clearly compromised rapid naming. Additionally, their
      parents had the most severe difficulties in rapid naming, a finding that suggests
      strong genetic liability. The findings show instability in the diagnosis of
      dyslexia. The members of the late-emerging group did not have a distinct early
      cognitive profile, so late-emerging dyslexia appears difficult to predict.
      Indeed, these children are at risk of not being identified and not receiving
      required support. This study suggests the need for continued monitoring of
      children's progress in literacy after the early school years. 

PMID- 25772427
TI  - Adolescent-Parent Attachment and Externalizing Behavior: The Mediating Role of
      Individual and Social Factors.
AB  - The aim of this study was to test whether the associations between adolescent
      parent attachment and externalizing problem behavior of adolescents were mediated
      by adolescent cognitive distortions, self-esteem, parental monitoring and
      association with deviant peers. A total of 102 adolescents (71 % male; aged 12-19
      years) at risk for developing delinquent behaviors reported on attachment,
      parental monitoring, aggressive and delinquent behavior and peers. Mediation
      effects were tested by using structural equation modeling. Different pathways
      were found depending on the type of externalizing behavior. The association
      between attachment and direct and indirect aggressive behavior was mediated by
      cognitive distortions. The relation between attachment and delinquency was
      mediated by deviant peers and parental monitoring. We argue that clinical
      practice should focus on the attachment relationship between adolescent and
      parents in order to positively affect risk and protective factors for
      adolescents' aggressive and delinquent behavior.

PMID- 25772428
TI  - A metallic superhard boron carbide: first-principles calculations.
AB  - A monoclinic BC3 phase (denoted M-BC3) has been predicted using first principles
      calculations. The M-BC3 structure is formed by alternately stacking sequences of
      metallic BC-layers and insulating C atom layers, thus, the structure exhibits two
      dimensional conductivity. Its stability has been confirmed by our calculations of
      the total energy, elastic constants, and phonon frequencies. The pressure of
      phase transition from graphite-like BC3 to M-BC3 is calculated to be 9.3 GPa, and
      the theoretical Vickers hardness of M-BC3 is 43.8 GPa, this value indicates that
      the compound is a potentially superhard material. By comparing Raman spectral
      calculations of M-BC3 and previously proposed structures with the experimental
      data, we speculate that the experimentally synthesized BC3 crystal may
      simultaneously contain M-BC3 and Pmma-b phases. 

PMID- 25772429
TI  - Hunt for the origin of allergy - comparing the Finnish and Russian Karelia.
AB  - The Finnish and Russian Karelia are adjacent areas in northern Europe, socio
      economically distinct but geoclimatically similar. The Karelia Allergy Study was
      commenced in 1998 to characterize the allergy profiles in the two areas. Allergy
      prevalence had increased in Finland since the early 1960s, but the situation in
      Russia was unknown. The key finding was that allergic symptoms and diseases were
      systematically more common in Finnish children and adults than in their Russian
      counterparts. For example, in the early 2000s, hay fever in school children was
      almost non-existent in Russian Karelia, and only 2% were sensitized to birch
      pollen compared with 27% in Finnish Karelia. Adult birth cohorts showed that
      among those born in the 1940s, the sensitization to pollens and pets was at the
      same low level in both countries, but among younger generation born in the late
      1970s, the difference was already manifold. Seropositivity to some pathogens,
      microbial content in house dust and drinking water seemed to confer allergy
      protection in Russia. In subsequent studies, it became apparent that on the
      Finnish side, healthy children had a more biodiverse living environment as well
      as greater diversity of certain bacterial classes on their skin than atopic
      children. Abundance of skin commensals, especially Acinetobacter
      (gammaproteobacteria), associated with anti-inflammatory gene expression in blood
      leucocytes. In vivo experiments with the mouse model demonstrated that
      intradermally applied Acinetobacter protected against atopic sensitization and
      lung inflammation. These observations support the notion that the epidemic of
      allergy and asthma results from reduced exposure to natural environments with
      rich microbiota, changed diet and sedentary lifestyle. Genetic studies have
      confirmed strong influence of lifestyle and environment. With our results from
      the Karelia study, a 10-year National Allergy Programme was started in 2008 to
      combat the epidemic in Finland. 

PMID- 25772430
TI  - Application of a discovery to targeted LC-MS proteomics approach to identify
      deregulated proteins associated with idiosyncratic liver toxicity in a rat model
      of LPS/diclofenac co-administration.
AB  - Increasing experimental and clinical evidence suggest a contribution of non-drug
      related risk factors (e.g., underlying disease, bacterial/viral infection) to
      idiosyncratic drug reactions (IDR). Our previous work showed that co-treatment
      with bacterial endotoxin (LPS) and therapeutic doses of diclofenac (Dcl), an
      analgesic associated with drug idiosyncrasy in patients, induced severe
      hepatotoxicity in rats. Here, we used an integrated discovery to targeted LC-MS
      proteomics approach to identify mechanistically relevant liver and plasma
      proteins modulated by LPS/Dcl treatment, potentially applicable as early markers
      for IDRs. Based on pre-screening results and their role in liver toxicity, 47
      liver and 15 plasma proteins were selected for targeted LC-MS analysis. LPS alone
      significantly changed the levels of 19 and 3 of these proteins, respectively. T
      kininogen-1, previously suggested as a marker of drug-induced liver injury, was
      markedly elevated in plasma after repeated Dcl treatment in the absence of
      hepatotoxicity, possibly indicating clinically silent stress. Dcl both alone and
      in combination with LPS, caused up-regulation of the ATP synthase subunits
      (ATP5J, ATPA, and ATPB), suggesting that Dcl may sensitize cells against
      additional stress factors, such as LPS through generation of mitochondrial
      stress. Additionally, depletion of plasma fibrinogen was observed in the co
      treatment group, consistent with an increased hepatic fibrin deposition and
      suspected contribution of the hemostatic system to IDRs. In contrast, several
      proteins previously suggested as liver biomarkers, such as clusterin, did not
      correlate with liver injury in this model. Taken together, these analyses
      revealed proteomic changes in a rat model of LPS/Dcl co-administration that could
      offer mechanistic insight and may serve as biomarkers or safety alert for a
      drug's potential to cause IDRs.

PMID- 25772431
TI  - Participation of divalent cation transporter DMT1 in the uptake of inorganic
      mercury.
AB  - Mercury (Hg) is found in food in various chemical forms, which differ in terms of
      accumulation, transport, and toxicity. Although methylmercury (CH3Hg) is the
      predominant mercury species in the diet, contributed mostly by seafood products,
      there is also a contribution of inorganic mercury [Hg(II)] from vegetables,
      cereals, and seafood products. The main pathway for exposure to mercury is oral,
      and therefore the gastrointestinal mucosa is the first barrier that the
      contaminant meets when it enters the systemic circulation. However, the transport
      mechanisms responsible for the process of mercury absorption are not known. The
      aim of this study is to evaluate the possible participation of divalent metal
      transporter 1 (DMT1) in Hg(II) intestinal uptake. For this purpose, we have used
      various complementary approaches. We have studied mercury acquisition in a
      Saccharomyces cerevisiae strain expressing murine DMT1. Moreover, we have
      evaluated the effect of a reduction of DMT1 expression in Caco-2 cells, by means
      of small interfering RNA and of treatment with hepcidin, on mercury uptake and
      transport. The results show that expression of the transporter DMT1 in yeast
      produces an increase in Hg(II) accumulation. Furthermore, a decrease in the
      levels of DMT1 mRNA in Caco-2 cells in various stages of differentiation leads to
      a reduction in cellular accumulation and apical-basolateral transport of Hg(II).
      These data point clearly to the mediation of the divalent cation transporter DMT1
      in the entry of Hg(II) into the intestinal epithelium. 

PMID- 25772432
TI  - Chemical structure-related mechanisms underlying in vivo genotoxicity induced by
      nitrofurantoin and its constituent moieties in gpt delta rats.
AB  - Nitrofurans are antimicrobial compounds containing a nitro group at the 5
      position of the furan ring and an amine or hydrazide side chain derivative. One
      member of the nitrofurans, nitrofurantoin (NFT), is a renal carcinogen in male
      rats despite its still controversial genotoxicity. We investigated chemical
      structure-related modes of action of NFT, and reporter gene mutation assays for
      NFT and its constituent moieties were performed. NFT, 5-nitro-2-furaldehyde
      (NFA), or 1-aminohydantoin (AHD) was administered to male F344 gpt delta rats by
      gavage for 4 or 13 weeks at a carcinogenic or the maximum tolerated dose. NFT
      caused a significant increase in gpt mutant frequency (MF) at 13 weeks with G
      base substitution mutations. An increase in gpt MF was also observed in the NFA
      treated group at 13 weeks, but not in the AHD-treated group. 8
      Hydroxydeoxyguanosine (8-OHdG) levels in the kidney DNA of NFT-treated rats were
      significantly increased after 4 weeks. NFT caused accumulation of hyaline
      droplets indicated by positive immunostaining and western blot analysis for
      alpha2u-globulin in the proximal tubules. An additional study, in which female
      gpt delta rats were given NFT at the same dose used for males, was performed to
      mitigate the effect of alpha2u-globulin. NFT exerted the same effects on female
      rat kidneys to the same extent as males in terms of gpt MF and 8-OHdG level.
      Thus, it is highly probable that the structure of the nitro furan plays a key
      role in NFT-induced genotoxicity and genotoxic mechanisms including oxidative DNA
      damage are involved in NFT-induced renal carcinogenesis. alpha2u-globulin
      mediated nephropathy may be a prerequisite for NFT-induced renal carcinogenesis
      in male rats, and additionally NFT could be a latent carcinogen in female rats
      and other animal species.

PMID- 25772433
TI  - PP2A-B56epsilon complex is involved in dephosphorylation of gamma-H2AX in the
      repair process of CPT-induced DNA double-strand breaks.
AB  - Phosphorylation of histone H2AX (gamma-H2AX) in response to DNA double-strand
      breaks (DSBs) should be eliminated from the sites of DNA damage to fulfill the
      DNA repair and release cells from the growth arrest. Previous study showed that
      protein phosphatase 2A (PP2A) interact with gamma-H2AX that lead to the
      dephosphorylation of gamma-H2AX. Here, we examined the effects of suppression of
      PP2A regulatory subunits on dephosphorylation of gamma-H2AX in human embryonic
      kidney epithelial cells (HEK) treated by topoisomerase I inhibitor camptothecin
      (CPT). We found that cells with suppression of B55alpha or B56epsilon were more
      sensitive to DNA damage agents. Suppression of B56epsilon led to persistence of
      gamma-H2AX, resulting in prolonged DSBs repair and increased chromatin
      instability measured by comet assay. In addition, the deficiency of B56epsilon
      impaired the cell cycle regulation and the DNA repair pathway of homologous
      recombination (HR). Notably, we detected that PP2A B56epsilon subunit was
      involved directly in dephosphorylation of gamma-H2AX and translocated from
      cytoplasm to nucleus upon the treatment of CPT. Our findings demonstrate that
      PP2A holoenzyme containing B56epsilon is responsible for the dephosphorylation of
      gamma-H2AX and regulation of DNA repair of DSBs induced by CPT.

PMID- 25772434
TI  - Brain perfusion in polysubstance users: relationship to substance and tobacco
      use, cognition, and self-regulation.
AB  - BACKGROUND: Brain perfusion is altered in both alcohol dependence and stimulant
      dependence. Although most substance users also abuse/depend on alcohol
      concurrently (polysubstance users; PSU), rigorous perfusion research in PSU is
      limited. Also, the relationships of perfusion abnormalities with cognition,
      impulsivity, or decision making are not well known. METHODS: Arterial spin
      labeling MRI and neuropsychological measures assessed perfusion levels and
      neurocognition in 20 alcohol-dependent individuals with comorbid-stimulant
      dependence (PSU), 26 individuals dependent on alcohol only (ALC), and 31
      light/non-drinking controls (LD). The patient groups included smokers and non
      smokers. RESULTS: ALC had lower perfusion than LD in subcortical and cortical
      brain regions including the brain reward/executive oversight system (BREOS).
      Contrary to our hypothesis, regional perfusion was generally not lower in PSU
      than ALC. However, smoking PSU had lower perfusion than smoking ALC in several
      regions, including BREOS. Lower BREOS perfusion related to greater drinking
      severity in smoking substance users and to greater smoking severity in smoking
      ALC. Lower regional perfusion in ALC and PSU correlated with worse performance in
      different cognitive domains; smoking status affected perfusion-cognition
      relationships in ALC only. Lower BREOS perfusion in both substance using groups
      related to higher impulsivity. CONCLUSION: Although regional perfusion was not
      decreased in PSU as a group, the combination of cigarette smoking and
      polysubstance use is strongly related to hypoperfusion in important cortical and
      subcortical regions. As lower perfusion relates to greater smoking severity,
      worse cognition and higher impulsivity, smoking cessation is warranted for
      treatment-seeking PSU and ALC.

PMID- 25772436
TI  - Risk factors for high levels of prescription drug misuse and illicit drug use
      among substance-using young men who have sex with men (YMSM).
AB  - BACKGROUND: Limited research has focused on prescription drug misuse among young
      men who have sex with men (YMSM), or investigated risk factors contributing to
      misuse. This study aims to investigate the relationship between multiple
      psychosocial risk factors (i.e., childhood abuse, discrimination, mental health
      distress) and prescription drug misuse among YMSM who are current substance
      users. METHODS: YMSM (N=191) who reported prescription drug misuse in the past 6
      months were recruited in Philadelphia between 2012 and 2013 to complete an
      anonymous survey assessing demographic information, substance use, and
      psychosocial factors. RESULTS: High levels of childhood physical abuse and
      perceived stress were associated with higher opioid misuse, while high levels of
      depression were associated with lower misuse of opioids. Those with higher levels
      of perceived stress were more likely to report higher tranquilizer misuse, while
      those with more experiences of social homophobia/racism and higher levels of
      depression and somatization reported higher stimulant misuse. Regarding
      demographic correlates, older participants were more likely than younger
      participants to report higher opioid misuse, while racial minorities were less
      likely than White participants to report higher misuse of tranquilizers,
      stimulants, and illicit drug use. Bisexual/heterosexual/other identified
      participants were more likely than gay identified participants to report higher
      misuse of all three classes of prescription drugs. CONCLUSIONS: Associations of
      risk factors with substance use among YMSM are complex and offer opportunities
      for additional research. Our findings show that prevention efforts must address
      substance use among YMSM in sync with psychosocial stressors.

PMID- 25772435
TI  - The relationship between cannabis involvement and suicidal thoughts and
      behaviors.
AB  - BACKGROUND: In the present study, we examined the relationship between cannabis
      involvement and suicidal ideation (SI), plan and attempt, differentiating the
      latter into planned and unplanned attempt, taking into account other substance
      involvement and psychopathology. METHODS: We used two community-based twin
      samples from the Australian Twin Registry, including 9583 individuals (58.5%
      female, aged between 27 and 40). The Semi-Structured Assessment of the Genetics
      of Alcoholism (SSAGA) was used to assess cannabis involvement which was
      categorized into: (0) no cannabis use (reference category); (1) cannabis use
      only; (2) 1-2 cannabis use disorder symptoms; (3) 3 or more symptoms. Separate
      multinomial logistic regression analyses were conducted for SI and suicide
      attempt with or without a plan. Twin analyses examined the genetic overlap
      between cannabis involvement and SI. RESULTS: All levels of cannabis involvement
      were related to SI, regardless of duration (odds ratios [ORs]=1.28-2.00, p<0.01).
      Cannabis use and endorsing >=3 symptoms were associated with unplanned (SANP;
      ORs=1.95 and 2.51 respectively, p<0.05), but not planned suicide attempts
      (p>0.10). Associations persisted even after controlling for other psychiatric
      disorders and substance involvement. Overlapping genetic (rG=0.45) and
      environmental (rE=0.21) factors were responsible for the covariance between
      cannabis involvement and SI. CONCLUSIONS: Cannabis involvement is associated,
      albeit modestly, with SI and unplanned suicide attempts. Such attempts are
      difficult to prevent and their association with cannabis use and cannabis use
      disorder symptoms requires further study, including in different samples and with
      additional attention to confounders.

PMID- 25772437
TI  - Perinatal substance use: a prospective evaluation of abstinence and relapse.
AB  - BACKGROUND: Substance use decreases in pregnancy but little prospective data are
      available on the rates of abstinence and relapse for specific substances. This
      study compared rates of abstinence in pregnancy and relapse postpartum for
      nicotine cigarettes, alcohol, marijuana, and cocaine. METHODS: Data from 152
      women drawn from a randomized controlled trial comparing psychological treatments
      for substance use in pregnancy were analyzed. Self-reports of substance use and
      urine for toxicology testing throughout pregnancy and 3-months, 12-months and 24
      months post-delivery were collected. Multivariate Cox models were used to compare
      rates of abstinence and relapse across substances. RESULTS: In pregnancy, 83% of
      all women achieved abstinence to at least one substance. The mean (SE) days to
      abstinence was 145.81 (9.17), 132.01 (6.17), 151.52 (6.24), and 148.91 (7.68) for
      cigarettes, alcohol, marijuana and cocaine, respectively. Participants were more
      likely to achieve abstinence from alcohol (HR 7.24; 95% CI 4.47-11.72), marijuana
      (HR 4.06; 95% CI 1.87-6.22), and cocaine (HR 3.41; 95% CI 2.53-6.51), than
      cigarettes. Postpartum, 80% of women abstinent in the last month of pregnancy
      relapsed to at least one substance. The mean days to relapse was 109.67 (26.34),
      127.73 (21.29), 138.35 (25.46), and 287.55 (95.85) for cigarettes, alcohol,
      marijuana and cocaine, respectively. Relapse to cocaine was only 34% (HR 0.34;
      95% CI 0.15-0.77) that of cigarettes. CONCLUSIONS: Pregnancy-related abstinence
      rates were high for all substances except cigarettes. Postpartum relapse was
      common, with cocaine using women being less likely to relapse after attaining
      abstinence compared to women using cigarettes, alcohol or marijuana.

PMID- 25772439
TI  - DNA damage-responsive transgene expression mediated by the p53 promoter with
      transcriptional amplification.
AB  - We constructed a DNA damage-responsive transgene expression system mediated by
      the p53 promoter. We incorporated a transactivation system to generate
      transcriptional amplification via a positive feedback loop. Higher levels of DNA
      damage-responsive transgene expression were observed when transactivation was
      active. 

PMID- 25772438
TI  - Effects of acute and repeated dosing of the synthetic cannabinoid CP55,940 on
      intracranial self-stimulation in mice.
AB  - BACKGROUND: Synthetic cannabinoids have emerged as a significant public health
      concern. To increase the knowledge of how these molecules interact on brain
      reward processes, we investigated the effects of CP55,940, a high efficacy
      synthetic CB1 receptor agonist, in a frequency-rate intracranial self-stimulation
      (ICSS) procedure. METHODS: The impact of acute and repeated administration (seven
      days) of CP55,940 on operant responding for electrical brain stimulation of the
      medial forebrain bundle was investigated in C57BL/6J mice. RESULTS: CP55,940
      attenuated ICSS in a dose-related fashion (ED50 (95% C.L.)=0.15 (0.12
      0.18)mg/kg). This effect was blocked by the CB1 receptor antagonist rimonabant.
      Tolerance developed quickly, though not completely, to the rate-decreasing
      effects of CP55,940 (0.3mg/kg). Abrupt discontinuation of drug did not alter
      baseline responding for up to seven days. Moreover, rimonabant (10mg/kg)
      challenge did not alter ICSS responding in mice treated repeatedly with CP55,940.
      CONCLUSIONS: The finding that CP55,940 reduced ICSS in mice with no evidence of
      facilitation at any dose is consistent with synthetic cannabinoid effects on ICSS
      in rats. CP55,940-induced ICSS depression was mediated through a CB1 receptor
      mechanism. Additionally, tolerance and dependence following repeated CP55,940
      administration were dissociable. Thus, CP55,940 does not produce reward-like
      effects in ICSS under these conditions.

PMID- 25772440
TI  - Age-dependent alterations in the cortical entrainment of subthalamic nucleus
      neurons in the YAC128 mouse model of Huntington's disease.
AB  - Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder
      that results in motor, cognitive and psychiatric abnormalities. Dysfunction in
      neuronal processing between the cortex and the basal ganglia is fundamental to
      the onset and progression of the HD phenotype. The corticosubthalamic hyperdirect
      pathway plays a crucial role in motor selection and blockade of neuronal activity
      in the subthalamic nucleus (STN) results in hyperkinetic movement abnormalities,
      similar to the motor symptoms associated with HD. The aim of the present study
      was to examine whether changes in the fidelity of information transmission
      between the cortex and the STN emerge as a function of phenotypic severity in the
      YAC128 mouse model of HD. We obtained in vivo extracellular recordings in the STN
      and concomitant electrocorticogram (ECoG) recordings during discrete brain states
      that reflected global cortical network synchronization or desynchronization. At
      early ages in YAC128 mice, both the cortex and the STN exhibited patterns of
      hyperexcitability. As symptom severity progressed, cortical entrainment of STN
      activity was disrupted and there was an increase in the proportion of non
      oscillating, tonically firing STN neurons that were less phase-locked to cortical
      activity. Concomitant to the dissipation of STN entrainment, there was a
      reduction in the evoked response of STN neurons to focal cortical stimulation.
      The spontaneous discharge of STN neurons in YAC128 mice also decreased with age
      and symptom severity. These results indicate dysfunction in the flow of
      information within the corticosubthalamic circuit and demonstrate progressive age
      related disconnection of the hyperdirect pathway in a transgenic mouse model of
      HD. 

PMID- 25772442
TI  - Early establishment of the phytoseiid mite Amblyseius swirskii (Acari:
      Phytoseiidae) on pepper seedlings in a Predator-in-First approach.
AB  - The establishment of biocontrol agents is critical for success of biological
      control strategies. Predator-in-First (PIF) is a prophylactic control strategy
      that aims to establish predators before the appearance of pests in an agro
      ecosystem. PIF uses the ability of generalist phytoseiid mites to survive,
      develop and reproduce on pollen and thus establish in the absence of prey. The
      early establishment of populations of natural enemies helps control the pests at
      their incipient stage of infestation. The current study was undertaken to screen
      pepper cultivars for their ability to support populations of the predatory mite
      Amblyseius swirskii Athias-Henriot in the absence of prey. Twenty-nine pepper
      cultivars (11 hot and 18 sweet) were tested through a series of experiments, and
      four cultivars (7141, 992-7141, FPP7039 and FPP9048) were found to sustain A.
      swirskii populations throughout the study period. The initial application of
      pollen was important for establishment and maintenance of the predatory mites
      within the greenhouse system. Among the three screening experiments, high
      densities of mites were obtained in the experiment where 20 mites were released
      per plant, even reaching densities of >100 mites/plant. Recovery of predatory
      mites was significantly higher (ca. 2-3 fold) on the four pepper cultivars when
      predatory mites were mass released using an indirect method (banker plants) than
      when they were released directly on the seedlings, suggesting an advantage of
      passive continuous release. Future work will evaluate the selected pepper
      cultivars with the PIF strategy under greenhouse and field production conditions.

PMID- 25772441
TI  - Neuroferritinopathy: From ferritin structure modification to pathogenetic
      mechanism.
AB  - Neuroferritinopathy is a rare, late-onset, dominantly inherited movement disorder
      caused by mutations in L-ferritin gene. It is characterized by iron and ferritin
      aggregate accumulation in brain, normal or low serum ferritin levels and high
      variable clinical feature. To date, nine causative mutations have been identified
      and eight of them are frameshift mutations determined by nucleotide(s) insertion
      in the exon 4 of L-ferritin gene altering the structural conformation of the C
      terminus of the L-ferritin subunit. Acting in a dominant negative manner,
      mutations are responsible for an impairment of the iron storage efficiency of
      ferritin molecule. Here, we review the main characteristics of
      neuroferritinopathy and present a computational analysis of some representative
      recently defined mutations with the purpose to gain new information about the
      pathogenetic mechanism of the disorder. This is particularly important as
      neuroferritinopathy can be considered an interesting model to study the
      relationship between iron, oxidative stress and neurodegeneration. 

PMID- 25772443
TI  - [Factors associated with influenza immunization in primary care health workers].
AB  - OBJECTIVE: To identify the influenza vaccination coverage in healthcare workers
      in primary care and to determine the factors associated with vaccination (2013
      2014 season). METHODS: A cross-sectional study was carried out among 287
      healthcare workers who completed a questionnaire that included questions about
      knowledge, beliefs and attitudes to influenza and vaccination. We estimated the
      vaccine coverage and identified the variables associated with vaccination of
      healthcare workers by using non-conditional logistic regression models. RESULTS:
      The participation rate was 47.2%. Vaccination coverage was 60.3% and was higher
      in workers older than 55 years, women and pediatricians. The factors associated
      with healthcare worker vaccination were the perception that vaccination confers
      protection (aOR: 11.1; 95%CI: 3.41-35.9) and the perception that it is effective
      (aOR: 7.5; 95%CI: 0.9-59.3). No association was found between receiving the
      vaccine and knowledge of influenza or vaccination. However, an association was
      found with prescribing vaccination to pregnant women, to persons older than 65
      years, and to immunosuppressed individuals. CONCLUSIONS: Strategies should be
      designed to increase coverage, based on changing negative attitudes of healthcare
      workers to vaccination.

PMID- 25772444
TI  - Insulin degludec/insulin aspart produces a dose-proportional glucose-lowering
      effect in subjects with type 1 diabetes mellitus.
AB  - AIMS: To evaluate the pharmacodynamic dose-response relationship of insulin
      degludec/insulin aspart (IDegAsp), a novel, soluble co-formulation of the ultra
      long-acting basal insulin, insulin degludec (IDeg), with the rapid-acting
      prandial insulin (IAsp), across different doses in patients with type 1 diabetes
      (T1DM). METHODS: This was a randomized, single-centre, double-blind, four-period,
      incomplete block, crossover trial. A cohort of 33 people with T1DM received
      single doses (0.4, 0.6 or 0.8 U/kg) of IDegAsp or the comparator, biphasic
      insulin aspart 30, in a randomized sequence of four treatment periods, each
      separated by a washout of 13-21 days. Pharmacodynamic response was assessed using
      a 26-h euglycaemic glucose clamp, with blood glucose stabilized at a target of
      5.5 mmol/l (100 mg/dl). RESULTS: A rapid onset of action and a distinct peak
      attributable to IAsp was observed in the glucose infusion rate (GIR) profile,
      followed by a separate, flat and stable basal glucose-lowering effect
      attributable to the IDeg component. The mean area under the GIR curve over 24 h
      (AUC(GIR,0-24 h)), and the mean maximum GIR (GIR(max)) increased with increasing
      dose level of IDegAsp. A dose-response relationship for IDegAsp was demonstrated
      for AUC(GIR,0-24 h) and GIR(max), indicating dose proportionality. A dose
      concentration relationship was also observed for both the basal and bolus
      components of IDegAsp. CONCLUSIONS: IDegAsp has a clear dose-response
      relationship, indicating the clinical potential for straightforward titration
      according to individual patient needs.

PMID- 25772445
TI  - Taste quality decoding parallels taste sensations.
AB  - In most species, the sense of taste is key in the distinction of potentially
      nutritious and harmful food constituents and thereby in the acceptance (or
      rejection) of food. Taste quality is encoded by specialized receptors on the
      tongue, which detect chemicals corresponding to each of the basic tastes (sweet,
      salty, sour, bitter, and savory [1]), before taste quality information is
      transmitted via segregated neuronal fibers [2], distributed coding across
      neuronal fibers [3], or dynamic firing patterns [4] to the gustatory cortex in
      the insula. In rodents, both hardwired coding by labeled lines [2] and flexible,
      learning-dependent representations [5] and broadly tuned neurons [6] seem to
      coexist. It is currently unknown how, when, and where taste quality
      representations are established in the cortex and whether these representations
      are used for perceptual decisions. Here, we show that neuronal response patterns
      allow to decode which of four tastants (salty, sweet, sour, and bitter)
      participants tasted in a given trial by using time-resolved multivariate pattern
      analyses of large-scale electrophysiological brain responses. The onset of this
      prediction coincided with the earliest taste-evoked responses originating from
      the insula and opercular cortices, indicating that quality is among the first
      attributes of a taste represented in the central gustatory system. These response
      patterns correlated with perceptual decisions of taste quality: tastes that
      participants discriminated less accurately also evoked less discriminated brain
      response patterns. The results therefore provide the first evidence for a link
      between taste-related decision-making and the predictive value of these brain
      response patterns.

PMID- 25772446
TI  - Aligning work and circadian time in shift workers improves sleep and reduces
      circadian disruption.
AB  - Sleep loss and circadian disruption-a state of misalignment between physiological
      functions and imposed sleep/wake behavior-supposedly play central roles in the
      etiology of shift work-related pathologies [1-4]. Circadian entrainment is,
      however, highly individual [5], resulting in different chronotypes [6, 7].
      Chronotype in turn modulates the effects of working times: compared to late
      chronotypes, earlier ones sleep worse and shorter and show higher levels of
      circadian misalignment during night shifts, while late types experience more
      sleep and circadian disruption than early types when working morning shifts [8].
      To promote sleep and reduce the mismatch between circadian and working time, we
      implemented a chronotype-adjusted (CTA) shift schedule in a factory. We abolished
      the most strenuous shifts for extreme chronotypes (i.e., mornings for late
      chronotypes, nights for early ones) and examined whether sleep duration and
      quality, social jetlag [9, 10], wellbeing, subjective stress perception, and
      satisfaction with leisure time improved in this schedule. Intermediate
      chronotypes (quartiles 2 and 3) served as a control group, still working morning
      (6:00-14:00), evening (14:00-22:00), and night (22:00-6:00) shifts, with two
      strenuous shifts (out of twelve per month) replaced by evening ones. We observed
      a significant increase of self-reported sleep duration and quality, along with
      increased wellbeing ratings on workdays among extreme chronotypes. The CTA
      schedule reduced overall social jetlag by 1 hr, did not alter stress levels, and
      increased satisfaction with leisure time (early types only). Chronotype-based
      schedules thus can reduce circadian disruption and improve sleep; potential long
      term effects on health and economic indicators need to be elucidated in future
      studies. 

PMID- 25772447
TI  - Chitin is endogenously produced in vertebrates.
AB  - Chitin, a biopolymer of N-acetylglucosamine, is abundant in invertebrates and
      fungi and is an important structural molecule [1, 2]. There has been a
      longstanding belief that vertebrates do not produce chitin; however, we have
      obtained compelling evidence to the contrary. Chitin synthase genes are present
      in numerous fishes and amphibians, and chitin is localized in situ to the lumen
      of the developing zebrafish gut, in epithelial cells of fish scales, and in at
      least three different cell types in larval salamander appendages. Chitin synthase
      gene knockdowns and various histochemical experiments in zebrafish further
      authenticated our results. Finally, a polysaccharide was extracted from scales of
      salmon that exhibited all the chemical hallmarks of chitin. Our data and analyses
      demonstrate the existence of endogenous chitin in vertebrates and suggest that it
      serves multiple roles in vertebrate biology.

PMID- 25772448
TI  - Moesin is a major regulator of centrosome behavior in epithelial cells with extra
      centrosomes.
AB  - Centrosome amplification has severe consequences during development and is
      thought to contribute to a variety of diseases such as cancer and microcephaly.
      However, the adverse effects of centrosome amplification in epithelia are still
      not known. Here, we investigate the consequences of centrosome amplification in
      the Drosophila wing disc epithelium. We found that epithelial cells exhibit
      mechanisms of clustering but also inactivation of extra centrosomes. Importantly,
      these mechanisms are not fully efficient, and both aneuploidy and cell death can
      be detected. Epithelial cells with extra centrosomes generate tumors when
      transplanted into WT hosts and inhibition of cell death results in tissue over
      growth and disorganization. Using SILAC-fly, we found that Moesin, a FERM domain
      protein, is specifically upregulated in wing discs with extra centrosomes. Moesin
      localizes to the centrosomes and mitotic spindle during mitosis, and we show that
      Moesin upregulation influences extra-centrosome behavior and robust bipolar
      spindle formation. This study provides a mechanistic explanation for the
      increased aneuploidy and transformation potential primed by centrosome
      amplification in epithelial tissues.

PMID- 25772449
TI  - A dynamin-actin interaction is required for vesicle scission during endocytosis
      in yeast.
AB  - Actin is critical for endocytosis in yeast cells, and also in mammalian cells
      under tension. However, questions remain as to how force generated through actin
      polymerization is transmitted to the plasma membrane to drive invagination and
      scission. Here, we reveal that the yeast dynamin Vps1 binds and bundles
      filamentous actin. Mutational analysis of Vps1 in a helix of the stalk domain
      identifies a mutant RR457-458EE that binds actin more weakly. In vivo analysis of
      Vps1 function demonstrates that the mutation disrupts endocytosis but not other
      functions of Vps1 such as vacuolar trafficking or peroxisome fission. The mutant
      Vps1 is stably expressed in cells and co-localizes with the endocytic reporters
      Abp1 and the amphiphysin Rvs167. Detailed analysis of individual endocytic patch
      behavior indicates that the mutation causes aberrant movements in later stages of
      endocytosis, consistent with a scission defect. Ultrastructural analysis of yeast
      cells using electron microscopy reveals a significant increase in invagination
      depth, further supporting a role for the Vps1-actin interaction during scission.
      In vitro analysis of the mutant protein demonstrates that--like wild-type Vps1-
      it is able to form oligomeric rings, but, critically, it has lost its ability to
      bundle actin filaments into higher-order structures. A model is proposed in which
      actin filaments bind Vps1 during invagination, and this interaction is important
      to transduce the force of actin polymerization to the membrane to drive
      successful scission.

PMID- 25772450
TI  - Parasite Exposure Drives Selective Evolution of Constitutive versus Inducible
      Defense.
AB  - In the face of infectious disease, organisms evolved a range of defense
      mechanisms, with a clear distinction between those that are constitutive (always
      active) and those that are inducible (elicited by parasites). Both defense
      strategies have evolved from each other, but we lack an understanding of the
      conditions that favor one strategy over the other. While it is hard to generalize
      about their degree of protection, it is possible to make generalizations about
      their associated fitness costs, which are commonly detected. By definition,
      constitutive defenses are always "on," and are therefore associated with a fixed
      cost, independent of parasite exposure. Inducible defenses, on the other hand,
      may lack costs in the absence of parasites but become costly when defense is
      elicited through processes such as immunopathology. Bacteria can evolve
      constitutive defense against phage by modification/masking of surface receptors,
      which is often associated with reduced fitness in the absence of phage. Bacteria
      can also evolve inducible defense using the CRISPR-Cas (clustered regularly
      interspaced short palindromic repeat, CRISPR associated) immune system, which is
      typically elicited upon infection. CRISPR-Cas functions by integrating phage
      sequences into CRISPR loci on the host genome. Upon re-infection, CRISPR
      transcripts guide cleavage of phage genomes. In nature, both mechanisms are
      important. Using a general theoretical model and experimental evolution, we tease
      apart the mechanism that drives their evolution and show that infection risk
      determines the relative investment in the two arms of defense.

PMID- 25772451
TI  - Induction of DNA methylation by artificial piRNA production in male germ cells.
AB  - Global DNA demethylation and subsequent de novo DNA methylation take place in
      mammalian male embryonic germ cells [1-3]. P-element-induced wimpy testis (PIWI)
      interacting RNAs (piRNAs), which are germline-specific small RNAs, have been
      postulated to be critically important for de novo DNA methylation of
      retrotransposon genes, and many proteins, including PIWI family proteins, play
      pivotal roles in this process [4-6]. In the embryonic mouse testis, two mouse
      PIWI proteins, mouse PIWI-like (MILI) and mouse PIWI2 (MIWI2), are involved in
      the biogenesis of piRNAs through the so-called ping-pong amplification cycle [7
      10], and long single-stranded RNAs transcribed from the gene regions of piRNA
      clusters have been proposed to be the initial material [11-16]. However, it
      remains unclear whether transcription from the piRNA clusters is required for the
      biogenesis of piRNAs. To answer this question, we developed a novel artificial
      piRNA production system by simple expression of sense and antisense EGFP mRNAs in
      embryonic male germ cells in the piRNA biogenesis phase. EGFP expression was
      silenced by piRNA-dependent DNA methylation, indicating that concomitant
      expression of sense and antisense RNA transcripts is necessary and sufficient for
      piRNA production and subsequent piRNA-dependent gene silencing. In addition, we
      demonstrated that this artificial piRNA induction paradigm could be applied to an
      endogenous gene essential for spermatogenesis, DNMT3L [3, 17, 18]. This study not
      only provides novel insights into the molecular mechanisms of piRNA production,
      but also presents an innovative strategy for inducing epigenetic modification in
      germ cells. 

PMID- 25772452
TI  - Shared decision making and screening: an ongoing dialogue informed by data.

PMID- 25772453
TI  - Minimally invasive resection of early lung cancers.
AB  - Low-dose computed tomography (LDCT) screening decreases lung cancer mortality in
      high-risk individuals and has now been approved and adopted for lung cancer
      screening in the United States. As more LDCT lung cancer screening programs are
      implemented, more patients with early-stage lung cancer who could benefit from
      surgical intervention will be identified. Although lobectomy currently remains
      the standard of care for early-stage non-small-cell lung cancer (NSCLC), thoracic
      surgeons are increasingly adopting minimally invasive surgery via thoracoscopy as
      a viable-and perhaps even preferred-approach for select lung cancer resections.
      Video-assisted thoracic surgery (VATS) lobectomy has been associated with
      decreased perioperative morbidity, and similar rates of locoregional recurrence
      and cancer-free survival can be achieved compared with the standard open surgical
      procedure. However, as lung cancers are detected at earlier stages, the optimal
      extent of lung resection for long-term cure continues to be investigated. For
      patients with very small-sized lung tumors and indolent lesions, cancer-free
      survival may not necessarily be compromised by undergoing less invasive
      approaches that intentionally resect less lung tissue, such as sublobar
      resections (eg, segmentectomy and wedge resection). This review looks at the
      current data and guidelines for thoracoscopic resection of stage I NSCLC and
      discusses the potential for limited lung resection in patients with the disease. 

PMID- 25772454
TI  - Smaller incisions for smaller cancers.

PMID- 25772455
TI  - Psychiatric care of lung cancer patients.

PMID- 25772456
TI  - Novel biologic agents for non-Hodgkin lymphoma and chronic lymphocytic leukemia
      part 1.
AB  - The incidence of non-Hodgkin lymphomas is on the rise worldwide. The aggressive
      non-Hodgkin lymphomas can potentially be cured with front-line therapy, but
      indolent ones, such as chronic lymphocytic leukemia/small lymphocytic lymphoma,
      cannot. Relapsed/refractory non-Hodgkin lymphomas have a poor overall outcome,
      typically with shorter responses after each relapse. Novel therapies are sought
      to improve outcomes in this patient population. This review discusses the
      promising new biologic therapies that have emerged over the last 5 years. Some
      have already achieved US Food and Drug Administration approval, while others are
      undergoing active investigation in order to ultimately gain approval. Here, in
      Part 1, we discuss monoclonal antibodies. In Part 2, we will discuss adoptive
      cellular immunotherapies, small-molecule inhibitors, and immunomodulatory agents.

PMID- 25772457
TI  - The era of immuno-oncology: are we there yet?

PMID- 25772458
TI  - Renal cancer management in a patient with chronic kidney disease.

PMID- 25772459
TI  - Bio-inspired design of hierarchical PDMS microstructures with tunable adhesive
      superhydrophobicity.
AB  - In this paper, bio-inspired PDMS films with different hierarchical
      microstructures were designed and tunable adhesive super-hydrophobicity was
      achieved on these films. The adhesive forces between a water droplet and the PDMS
      film can be adjusted from extremely low (about 8.3 MUN) to very high (about 57
      MUN), and the tunable effect can be ascribed to different wetting states for the
      water droplets that result from different microstructures on the films.
      Noticeably, the obtained super-hydrophobic surfaces are acid/alkali-resisting,
      and water droplets with different pH values have similar contact angles and
      adhesive forces on the same surface. Finally, the application of the obtained
      surfaces for microdroplet transportation and self-cleaning are also discussed.
      The results reported herein provide a new method to obtain super-hydrophobic
      surfaces with controlled adhesion, and significantly improve our understanding of
      the relationship between surface adhesion, surface microstructures and the
      fabrication principle of tunable adhesive super-hydrophobic surfaces. 

PMID- 25772460
TI  - A subspace-based coil combination method for phased-array magnetic resonance
      imaging.
AB  - PURPOSE: Coil-by-coil reconstruction methods are followed by coil combination to
      obtain a single image representing a spin density map. Typical coil combination
      methods, such as square-root sum-of-squares and adaptive coil combining, yield
      images that exhibit spatially varying modulation of image intensity. Existing
      practice is to first combine coils according to a signal-to-noise criterion, then
      postprocess to correct intensity inhomogeneity. If inhomogeneity is severe,
      however, intensity correction methods can yield poor results. The purpose of this
      article is to present an alternative optimality criterion for coil combination;
      the resulting procedure yields reduced intensity inhomogeneity while preserving
      contrast. THEORY AND METHODS: A minimum mean squared error criterion is adopted
      for combining coils via a subspace decomposition. Techniques are compared using
      both simulated and in vivo data. RESULTS: Experimental results for simulated and
      in vivo data demonstrate lower bias, higher signal-to-noise ratio (about 7*) and
      contrast-to-noise ratio (about 2*), compared to existing coil combination
      techniques. CONCLUSION: The proposed coil combination method is noniterative and
      does not require estimation of coil sensitivity maps or image mask; the method is
      particularly suited to cases where intensity inhomogeneity is too severe for
      existing approaches.

PMID- 25772461
TI  - Can size 20, .04 taper rotary files reproducibly create a glide path for the self
      adjusting file? An ex vivo study in MB canals of mandibular molars.
AB  - AIM: To test and compare the effectiveness and safety of two size 20, .04 taper
      rotary files that were used to create a glide path for the self-adjusting file
      (SAF) in curved canals of mandibular molars. METHODOLOGY: Forty mandibular molars
      with curved mesial roots and narrow MB root canals were selected based on a
      passage of size 15 K-files to WL; size 20 K-files could not reach WL. Only roots
      with no visible microcracks were included. Two types of size 20 rotary files were
      used for glide path preparation, the new Pre-SAF size 20, .04 taper file and the
      ProFile size 20, .04 taper, which served as the reference and control. Both files
      were used with 3-4 pecking strokes, which brought them to WL. Two parameters were
      tested whether the glide path allowed manual insertion of a 1.5-mm SAF file to WL
      and whether the procedure caused microcracks in the root dentine. Paired t-tests
      were used to compare the groups. RESULTS: Glide path preparation with both files
      allowed the manual insertion of the SAF file to WL in all 20 root canals, with no
      difference between the two groups. No cracks were detected after the procedure in
      any of the roots in either group. CONCLUSIONS: Both types of size 20, .04 taper
      rotary files were effective for glide path preparation for the SAF file in curved
      canals. Neither file type caused microcracks in root dentine.

PMID- 25772462
TI  - A density explanation of valence asymmetries in recognition memory.
AB  - The density hypothesis states that positive information is more similar than
      negative information, resulting in higher density of positive information in
      mental representations. The present research applies the density hypothesis to
      recognition memory to explain apparent valence asymmetries in recognition memory,
      namely, a recognition advantage for negative information. Previous research
      explained this negativity advantage on the basis of valence-induced affect. We
      predicted that positive information's higher density impairs recognition
      performance. Two old-new word recognition experiments tested whether differential
      density between positive and negative stimuli creates a negativity advantage in
      recognition memory, over and above valence-induced affect. In Experiment 1,
      participants better discriminated negative word stimuli (i.e., less false alarms)
      and showed a response bias towards positive words. Regression analyses showed the
      asymmetry to be function of density and not of valence. Experiment 2 varied
      stimulus density orthogonal to valence. Again, discriminability and response bias
      were a function of density and not of valence. We conclude that the higher
      density of positive information causes an apparent valence asymmetry in
      recognition memory. 

PMID- 25772463
TI  - Junctional Beats and Short HV Interval: What More Do You Need?

PMID- 25772465
TI  - How do Egyptian gynecologists manage infertility? Cross-sectional study.
AB  - AIM: The purpose of this study was to determine the knowledge and practices of a
      sample of Egyptian gynecologists with respect to the management and diagnosis of
      infertility and the variation between gynecologists according to qualifications.
      METHODS: A questionnaire assessing knowledge, practice habits, and perception
      towards the management of infertility was distributed to gynecologists. Data were
      collected during the annual meeting of the Clinical Society of Obstetricians and
      Gynaecologists, which was held in Mansoura, Egypt. Two hundred and fifty-eight
      gynecologists attended the meeting. Two researchers distributed the
      questionnaires to the clinicians. Clinician responses to questions were assessed
      according to the National Institute of Clinical Excellence (NICE) fertility
      guidelines. The main outcome measures were knowledge and adherence of
      gynecologists to NICE infertility guidelines. RESULTS: Significant differences
      were identified between clinicians with Master degree/Diploma and those with
      higher degrees (MD or PhD) with regard to knowledge as well as management options
      of different causes of infertility. CONCLUSION: There is a need to develop and
      implement national strategies, including mandatory update of reproductive
      medicine curricula as well as providing continuous professional development
      programs, in order to boost infertility management in developing countries such
      as Egypt.

PMID- 25772464
TI  - Benzodiazepines alter nucleotide and nucleoside hydrolysis in zebrafish (Danio
      rerio) brain.
AB  - Anxiety is characterized by unpleasant bodily sensations, such as pounding heart
      and intense fear. The therapy involves the administration of benzodiazepine
      drugs. Purinergic signaling participates in the induction of several behavioral
      patterns and their actions are inactivated by ectonucleotidases and adenosine
      deaminase (ADA). Since there is evidence about the involvement of purinergic
      system in the actions mediated by benzodiazepines, we evaluated the effects in
      vitro and in vivo of administration of diazepam and midazolam on nucleoside
      triphosphate diphosphohydrolases, ecto-5'-nucleotidase, and ADA activities in
      zebrafish brain, followed by the analysis of gene expression pattern of these
      enzymes and adenosine receptors (A1, A2a1, A2a2, A2b). The in vitro studies
      demonstrated that diazepam decreased ATP (66 % for 500 uM) and ADP hydrolysis (40
      54 % for 10-500 uM, respectively). Midazolam decreased ATP (16-71 % for 10-500
      uM, respectively) and ADP (48-73.5 % for 250-500 uM, respectively) hydrolysis as
      well as the ecto-ADA activity (26-27.5 % for 10-500 uM, respectively). AMP
      hydrolysis was decreased in animals treated with of 0.5 and 1 mg/L midazolam (32
      and 36 %, respectively). Diazepam and midazolam decreased the ecto-ADA activity
      at 1.25 mg/L and 1 mg/L (31 and 33 %, respectively), but only 0.1 mg/L midazolam
      induced an increase (40 %) in cytosolic ADA. The gene expression analysis
      demonstrated changes on ecto-5'-nucleotidase, A1, A2a1, A2a2, and A2b mRNA
      transcript levels after acute treatment with benzodiazepines. These findings
      demonstrated that benzodiazepine exposure induces a modulation of extracellular
      nucleotide and nucleoside metabolism, suggesting the purinergic signaling may be,
      at least in part, related to benzodiazepine effects.

PMID- 25772466
TI  - Enhanced resistance to blister blight in transgenic tea (Camellia sinensis [L.]
      O. Kuntze) by overexpression of class I chitinase gene from potato (Solanum
      tuberosum).
AB  - Tea is the second most consumed beverage in the world. A crop loss of up to 43 %
      has been reported due to blister blight disease of tea caused by a fungus,
      Exobasidium vexans. Thus, it directly affects the tea industry qualitatively and
      quantitatively. Solanum tuberosum class I chitinase gene (AF153195) is a plant
      pathogenesis-related gene. It was introduced into tea genome via Agrobacterium
      mediated transformation with hygromycin phosphotransferase (hpt) gene conferring
      hygromycin resistance as plant selectable marker. A total of 41 hygromycin
      resistant plantlets were obtained, and PCR analysis established 12 plantlets
      confirming about the stable integration of transgene in the plant genome. Real
      time PCR detected transgene expression in four transgenic plantlets (T28, C57,
      C9, and T31). Resistance to biotrophic fungal pathogen, E. vexans, was tested by
      detached leaf infection assay of greenhouse acclimated plantlets. An inhibitory
      activity against the fungal pathogen was evident from the detached leaves from
      the transformants compared with the control. Fungal lesion formed on control
      plantlet whereas the transgenic plantlets showed resistance to inoculated fungal
      pathogen by the formation of hypersensitivity reaction area. This result suggests
      that constitutive expression of the potato class I chitinase gene can be
      exploited to improve resistance to fungal pathogen, E. vexans, in economical
      perennial plantation crop like tea.

PMID- 25772467
TI  - Unlocking the diversity of alkaloids in Catharanthus roseus: nuclear localization
      suggests metabolic channeling in secondary metabolism.
AB  - The extraordinary chemical diversity of the plant-derived monoterpene indole
      alkaloids, which include vinblastine, quinine, and strychnine, originates from a
      single biosynthetic intermediate, strictosidine aglycone. Here we report for the
      first time the cloning of a biosynthetic gene and characterization of the
      corresponding enzyme that acts at this crucial branchpoint. This enzyme, an
      alcohol dehydrogenase homolog, converts strictosidine aglycone to the
      heteroyohimbine-type alkaloid tetrahydroalstonine. We also demonstrate how this
      enzyme, which uses a highly reactive substrate, may interact with the upstream
      enzyme of the pathway. 

PMID- 25772468
TI  - A small molecule inhibitor of ATPase activity of HSP70 induces apoptosis and has
      antitumor activities.
AB  - The heat shock protein HSP70 plays antiapoptotic and oncogenic roles, and thus
      its inhibition has been recognized as a potential avenue for anticancer therapy.
      Here we describe the small molecule, apoptozole (Az), which inhibits the ATPase
      activity of HSP70 by binding to its ATPase domain and, as a result, induces an
      array of apoptotic phenotypes in cancer cells. Affinity chromatography provides
      evidence that Az binds HSP70 but not other types of heat shock proteins including
      HSP40, HSP60, and HSP90. We also demonstrate that Az induces cancer cell death
      via caspase-dependent apoptosis by disrupting the interaction of HSP70 with APAF
      1. Animal studies indicate that Az treatment retards tumor growth in a xenograft
      mouse model without affecting mouse viability. These studies suggest that Az will
      aid the development of new cancer therapies and serve as a chemical probe to gain
      a better understanding of the diverse functions of HSP70.

PMID- 25772469
TI  - The reason why thin-film silicon grows layer by layer in plasma-enhanced chemical
      vapor deposition.
AB  - Thin-film Si grows layer by layer on Si(001)-(2 * 1):H in plasma-enhanced
      chemical vapor deposition. Here we investigate the reason why this occurs by
      using quantum chemical molecular dynamics and density functional theory
      calculations. We propose a dangling bond (DB) diffusion model as an alternative
      to the SiH3 diffusion model, which is in conflict with first-principles
      calculation results and does not match the experimental evidence. In our model,
      DBs diffuse rapidly along an upper layer consisting of Si-H3 sites, and then
      migrate from the upper layer to a lower layer consisting of Si-H sites. The
      subsequently incident SiH3 radical is then adsorbed onto the DB in the lower
      layer, producing two-dimensional growth. We find that DB diffusion appears
      analogous to H diffusion and can explain the reason why the layer-by-layer growth
      occurs. 

PMID- 25772470
TI  - In vivo human cardiac shortening and lengthening velocity is region dependent and
      not coupled with heart rate: 'longitudinal' strain rate markedly underestimates
      apical contribution.
AB  - NEW FINDINGS: What is the central question of this study? Regulation of cardiac
      function is typically achieved by changes in heart rate (HR) and cardiac
      shortening velocity (strain rate; SR), but their interdependence in vivo remains
      poorly understood. What is the main finding and its importance? Using resistance
      exercise to increase heart rate and arterial resistance physiologically in humans
      and measuring regional cardiac SR (at the base and apex), we found that HR and SR
      were not strictly coupled because SR at the base and apex responded differently,
      despite the same HR. Importantly, our data show that the region-averaged
      'longitudinal' SR, which is currently popular in the clinical setting, markedly
      underestimates the contribution of the apex. The fundamental importance of
      cardiac shortening and lengthening velocity (i.e. strain rate; SR) has been
      demonstrated in vitro. Currently, the interdependence between in vivo SR and HR
      is poorly understood because studies have typically assessed region-averaged
      'longitudinal' strain rate, which is likely to underestimate the apical
      contribution, and have used non-physiological interventions that may also have
      been influenced by multicollinearity caused by concomitant reductions in arterial
      resistance. Resistance exercise acutely raises HR, blood pressure and arterial
      resistance and transiently disassociates these cardiovascular factors following
      exercise. Therefore, we measured SR, HR, blood pressure and arterial resistance
      in nine healthy men (aged 20 +/- 1 years) immediately before, during and after
      double-leg-press exercise at 30 and 60% of maximal strength. Resistance exercise
      caused a disproportionate SR response at the left ventricular base and apex
      (interaction effect, P < 0.05). Consequently, associations between HR and
      regional peak SR were inconsistent and mostly very weak (r(2)  = 0.0004-0.24).
      Likewise, the areas under the curve for systolic and diastolic SR and their
      relationship with systolic and diastolic duration were variable and weak.
      Importantly, region-averaged 'longitudinal' SR was identical to basal SR, thus,
      markedly underestimating the apical contribution. In conclusion, in vivo HR and
      SR are not strictly coupled in healthy humans, which is explained by the region
      specific responses of SR that are not captured by 'longitudinal SR'. This novel
      observation emphasizes the independent role of in vivo SR in overall cardiac
      function during stress and may cause a 'revival' of SR as a marker of regional
      left ventricular (dys)function.

PMID- 25772471
TI  - Targeted correction and restored function of the CFTR gene in cystic fibrosis
      induced pluripotent stem cells.
AB  - Recently developed reprogramming and genome editing technologies make possible
      the derivation of corrected patient-specific pluripotent stem cell sources
      potentially useful for the development of new therapeutic approaches. Starting
      with skin fibroblasts from patients diagnosed with cystic fibrosis, we derived
      and characterized induced pluripotent stem cell (iPSC) lines. We then utilized
      zinc-finger nucleases (ZFNs), designed to target the endogenous CFTR gene, to
      mediate correction of the inherited genetic mutation in these patient-derived
      lines via homology-directed repair (HDR). We observed an exquisitely sensitive,
      homology-dependent preference for targeting one CFTR allele versus the other. The
      corrected cystic fibrosis iPSCs, when induced to differentiate in vitro,
      expressed the corrected CFTR gene; importantly, CFTR correction resulted in
      restored expression of the mature CFTR glycoprotein and restoration of CFTR
      chloride channel function in iPSC-derived epithelial cells. 

PMID- 25772472
TI  - An in vivo requirement for the mediator subunit med14 in the maintenance of stem
      cell populations.
AB  - The Mediator complex has recently been shown to be a key player in the
      maintenance of embryonic and induced pluripotent stem cells. However, the in vivo
      consequences of loss of many Mediator subunits are unknown. We identified med14
      as the gene affected in the zebrafish logelei (log) mutant, which displayed a
      morphological arrest by 2 days of development. Surprisingly, microarray analysis
      showed that transcription was not broadly affected in log mutants. Indeed, log
      cells transplanted into a wild-type environment were able to survive into
      adulthood. In planarians, RNAi knockdown demonstrated a requirement for med14 and
      many other Mediator components in adult stem cell maintenance and regeneration.
      Multiple stem/progenitor cell populations were observed to be reduced or absent
      in zebrafish med14 mutant embryos. Taken together, our results show a critical,
      evolutionarily conserved, in vivo function for Med14 (and Mediator) in stem cell
      maintenance, distinct from a general role in transcription. 

PMID- 25772474
TI  - Calorie restriction, endothelial function and blood pressure homeostasis.

PMID- 25772473
TI  - KLF4 N-terminal variance modulates induced reprogramming to pluripotency.
AB  - As the quintessential reprogramming model, OCT3/4, SOX2, KLF4, and c-MYC re-wire
      somatic cells to achieve induced pluripotency. Yet, subtle differences in
      methodology confound comparative studies of reprogramming mechanisms. Employing
      transposons, we systematically assessed cellular and molecular hallmarks of mouse
      somatic cell reprogramming by various polycistronic cassettes. Reprogramming
      responses varied in the extent of initiation and stabilization of transgene
      independent pluripotency. Notably, the cassettes employed one of two KLF4
      variants, differing only by nine N-terminal amino acids, which generated
      dissimilar protein stoichiometry. Extending the shorter variant by nine N
      terminal amino acids or augmenting stoichiometry by KLF4 supplementation rescued
      both protein levels and phenotypic disparities, implicating a threshold in
      determining reprogramming outcomes. Strikingly, global gene expression patterns
      elicited by published polycistronic cassettes diverged according to each KLF4
      variant. Our data expose a Klf4 reference cDNA variation that alters
      polycistronic factor stoichiometry, predicts reprogramming hallmarks, and guides
      comparison of compatible public data sets. 

PMID- 25772475
TI  - Cellular localization of uranium in the renal proximal tubules during acute renal
      uranium toxicity.
AB  - Renal toxicity is a hallmark of uranium exposure, with uranium accumulating
      specifically in the S3 segment of the proximal tubules causing tubular damage. As
      the distribution, concentration and dynamics of accumulated uranium at the
      cellular level is not well understood, here, we report on high-resolution
      quantitative in situ measurements by high-energy synchrotron radiation X-ray
      fluorescence analysis in renal sections from a rat model of uranium-induced acute
      renal toxicity. One day after subcutaneous administration of uranium acetate to
      male Wistar rats at a dose of 0.5 mg uranium kg(-1) body weight, uranium
      concentration in the S3 segment of the proximal tubules was 64.9 +/- 18.2 ug g(
      1) , sevenfold higher than the mean renal uranium concentration (9.7 +/- 2.4 ug
      g(-1) ). Uranium distributed into the epithelium of the S3 segment of the
      proximal tubules and highly concentrated uranium (50-fold above mean renal
      concentration) in micro-regions was found near the nuclei. These uranium levels
      were maintained up to 8 days post-administration, despite more rapid reductions
      in mean renal concentration. Two weeks after uranium administration, damaged
      areas were filled with regenerating tubules and morphological signs of tissue
      recovery, but areas of high uranium concentration (100-fold above mean renal
      concentration) were still found in the epithelium of regenerating tubules. These
      data indicate that site-specific accumulation of uranium in micro-regions of the
      S3 segment of the proximal tubules and retention of uranium in concentrated areas
      during recovery are characteristics of uranium behavior in the kidney.

PMID- 25772477
TI  - Chemical toxicology in China: a special issue.

PMID- 25772478
TI  - Uptake of Dietary Sodium Restriction by Overweight and Obese Patients After
      Cardiac Revascularization.
AB  - PURPOSE: High sodium intake increases the risk of cardiovascular diseases.
      Cardiac patients are recommended a daily sodium restriction of <=1,500 mg. The
      purpose of this article is to describe daily sodium intake and sodium restriction
      adherence and its correlates in cardiac rehabilitation (CR) program participants
      following cardiac revascularizations. DESIGN: This is a descriptive correlational
      study. METHODS: A subanalysis was performed using the data collected from a
      randomized controlled trial to determine the effect of a 12-week weight
      management intervention. FINDINGS: The average daily sodium intake was 3,020 mg
      +/- 1,134 at baseline, 4,047 mg +/-1,517 at 4 months, and 4,399 mg +/- 1,722 at 6
      months. The adherence rates were 4.8% at baseline and zero at 4 and 6 months. The
      factors influencing daily sodium intake were identified. CONCLUSION: The CR
      program participants failed to adhere to the sodium restriction guidelines.
      CLINICAL RELEVANCE: Rehabilitation nurses need to identify effective strategies
      to educate CR participants and their family members regarding dietary sodium
      adherence in CR participants.

PMID- 25772479
TI  - Species interactions and chemical stress: combined effects of intraspecific and
      interspecific interactions and pyrene on Daphnia magna population dynamics.
AB  - Species interactions are often suggested as an important factor when assessing
      the effects of chemicals on higher levels of biological organization.
      Nevertheless, the contribution of intraspecific and interspecific interactions to
      chemical effects on populations is often overlooked. In the present study,
      Daphnia magna populations were initiated with different levels of intraspecific
      competition, interspecific competition, and predation and exposed to pyrene
      pulses. Generalized linear models were used to test which of these factors
      significantly explained population size and structure at different time points.
      Pyrene had a negative effect on total population densities, with effects being
      more pronounced on smaller D. magna individuals. Among all species interactions
      tested, predation had the largest negative effect on population densities.
      Predation and high initial intraspecific competition were shown to interact
      antagonistically with pyrene exposure. This was attributed to differences in
      population structure before pyrene exposure and pyrene-induced reductions in
      predation pressure by Chaoborus sp. larvae. The present study provides empirical
      evidence that species interactions within and between populations can alter the
      response of aquatic populations to chemical exposure. Therefore, such
      interactions are important factors to be considered in ecological risk
      assessments.

PMID- 25772476
TI  - Mapping complex traits as a dynamic system.
AB  - Despite increasing emphasis on the genetic study of quantitative traits, we are
      still far from being able to chart a clear picture of their genetic architecture,
      given an inherent complexity involved in trait formation. A competing theory for
      studying such complex traits has emerged by viewing their phenotypic formation as
      a "system" in which a high-dimensional group of interconnected components act and
      interact across different levels of biological organization from molecules
      through cells to whole organisms. This system is initiated by a machinery of DNA
      sequences that regulate a cascade of biochemical pathways to synthesize
      endophenotypes and further assemble these endophenotypes toward the end-point
      phenotype in virtue of various developmental changes. This review focuses on a
      conceptual framework for genetic mapping of complex traits by which to delineate
      the underlying components, interactions and mechanisms that govern the system
      according to biological principles and understand how these components function
      synergistically under the control of quantitative trait loci (QTLs) to comprise a
      unified whole. This framework is built by a system of differential equations that
      quantifies how alterations of different components lead to the global change of
      trait development and function, and provides a quantitative and testable platform
      for assessing the multiscale interplay between QTLs and development. The method
      will enable geneticists to shed light on the genetic complexity of any biological
      system and predict, alter or engineer its physiological and pathological states. 

PMID- 25772480
TI  - Pilot Study Evaluating a Rat Model of Radiation-induced Erectile Dysfunction
      Using an Image-guided Microirradiator.
AB  - OBJECTIVE: To establish a feasible rat model of radiation-induced erectile
      dysfunction after targeted prostate irradiation using an image-guided irradiation
      unit specially designed for small-animal radiation research. METHODS: The X-RAD
      225Cx research platform was used in the present study. We first performed quality
      assurance testing using a rat cadaver. After confirming dosimetry, 24 age
      matched, young, adult, male rats were assigned to sham radiation or radiation to
      the prostate with doses of 15, 20, or 25 Gy. To confirm appropriate prostate
      irradiation, physiological erectile function was evaluated using intracavernous
      pressure (ICP) measurements with cavernous nerve electrical stimulation at 9
      weeks after radiotherapy. Each animal was weighed at the time of ICP measurement.
      In addition, we investigated the cyclic guanosine monophosphate level in the
      penile cavernosa using a commercial enzyme-linked immunosorbent assay kit.
      RESULTS: Quality assurance results confirmed the accuracy of the irradiation
      technique. Dose-dependent decreases in ICP in irradiated rats were observed
      without major toxicity. No difference in body weight was noted among the
      experimental groups. Cyclic guanosine monophosphate levels were significantly
      decreased in the group that received 25 Gy compared with the age-matched sham
      irradiated group. CONCLUSION: High-precision imaging and targeting capabilities
      provided by the micro-IGRT platform enable us to develop a reproducible animal
      model of radiation-induced erectile dysfunction in prostate cancer research.

PMID- 25772481
TI  - Effect of Ginkgo biloba Extract (EGb-761) on Recovery of Erectile Dysfunction in
      Bilateral Cavernous Nerve Injury Rat Model.
AB  - OBJECTIVE: To investigate whether the therapeutic effect of Ginkgo biloba extract
      (GBE) in a rat model can improve erectile dysfunction after bilateral cavernous
      nerve injury. METHODS: Forty-three male Sprague-Dawley rats underwent cavernous
      nerve crush injury and were randomized into 4 groups, including: vehicle only,
      high-dose GBE, medium-dose GBE, and low-dose GBE. Eight animals underwent sham
      operation. Four weeks later, erectile function was assessed by cavernous nerve
      electrostimulation, and penile tissue was collected for histologic analysis.
      RESULTS: Significant recovery of erectile function was observed in the high-dose
      GBE group in a dose-dependent manner as compared with the vehicle-only group (P
      <.001). The high-dose GBE group had a significant increase in neurofilament-1
      expression (P <.001), preservation of neural nitric oxide synthase nerve fibers
      of the dorsal penile nerve (P <.05), and increased smooth muscle cell content (P
      <.001) compared with the vehicle-only group. In addition, high-dose GBE markedly
      augments the smooth muscle-to-collagen ratio (P <.05) and reduces the apoptotic
      index. CONCLUSION: Administration of GBE increases neuron survival and preserves
      the neural nitric oxide synthase nerve fiber and contents of the corpus
      cavernosum after bilateral cavernous nerve injury. These implications indicate
      the beneficial effects of GBE use in the repair of the cavernous nerve and
      recovery of erectile function after radical prostatectomy.

PMID- 25772482
TI  - Hybridization-induced Ag(I) dissociation from an immobilization-free and label
      free hairpin DNA: toward a novel electronic monitoring platform.
AB  - A novel silver ion (Ag(+))-assisted hairpin DNA through C-Ag(+)-C coordination
      chemistry was designed for immobilization-free and label-free electrochemical
      monitoring of human immunodeficiency virus (HIV) DNA on a negatively charged
      indium-tin oxide electrode, based on hybridization-induced dissociation of silver
      ions from the hairpin DNA. 

PMID- 25772483
TI  - Alterations in gene promoter methylation and transcript expression induced by
      cisplatin in comparison to 5-Azacytidine in HeLa and SiHa cervical cancer cell
      lines.
AB  - Despite recent advances in treatment, cervical cancer still remains one of the
      leading causes of cancer related mortality among women worldwide including India.
      Chemoradiation treatment is the standard-of-care which involves administration of
      cisplatin, a radiosensitizer along with radiation. The epigenetic changes induced
      by cisplatin are not known and so we designed this in vitro experimental study.
      We evaluated the changes induced by cisplatin administration in gene promoter
      methylation and the transcript levels of set of 7 genes and compared it to the
      changes induced by 5-Azacytidine, a known demethylating agent in two cervical
      cancer cell lines: HeLa (adenocarcinoma derived) and SiHa (squamous cell
      carcinoma derived) cell lines. Overall, there was a pronounced cytotoxic and
      growth inhibitory effect of both the drugs alone and in combination for both the
      cell lines which was dose and time dependent. Cisplatin as well as 5-Azacytidine
      treatment affected gene promoter methylation status resulting in demethylation
      and re-expression of the genes under investigation which was more pronounced in
      case of SiHa cells as compared to HeLa cells. Further, both the drugs acted in
      synergism as evident from their combination treatment. Therefore, at the cellular
      level, cisplatin and 5-Azacytidine can induce epigenetic changes in gene promoter
      methylation with altered expression which can have implications for treatment of
      cervical cancer.

PMID- 25772484
TI  - Decrease of serum adenine nucleotide hydrolysis in an irritant contact dermatitis
      mice model: potential P2X7R involvement.
AB  - Extracellular adenosine 5'-triphosphate (ATP) has significant effects on a
      variety of pathological conditions and it is the main physiological agonist of
      P2X7 purinergic receptor (P2X7R). It is known that ATP acting via purinergic
      receptors plays a relevant role on skin inflammation, and P2X7R is required to
      neutrophil recruitment in a mice model of irritant contact dermatitis (ICD).The
      present study investigated the effects of chemical irritant croton oil (CrO) upon
      ATP, ADP, and AMP hydrolysis in mice blood serum, and the potential involvement
      of P2X7R. The topical application CrO induced a decrease on soluble ATP/ADPase
      activities (~50 %), and the treatment with the selective P2X7R antagonist,
      A438079, reversed these effects to control level. Furthermore, we showed that CrO
      decreased cellular viability (52.6 % +/- 3.9) in relation to the control and
      caused necrosis in keratinocytes (PI positive cells). The necrosis induced by CrO
      was prevented by the pre-treatment with the selective P2X7R antagonist A438079.
      The results presented herein suggest that CrO exerts an inhibitory effect on the
      activity of ATPDase in mouse serum, reinforcing the idea that ICD has a
      pathogenic mechanism dependent of CD39. Furthermore, it is tempting to suggest
      that P2X7R may act as a controller of the extracellular levels of ATP.

PMID- 25772485
TI  - MiR-129-2 functions as a tumor suppressor in glioma cells by targeting HMGB1 and
      is down-regulated by DNA methylation.
AB  - MicroRNA (miRNA) dysregulation is causally related to cancer development and
      progression, and recent reports have revealed that DNA methylation constitutes an
      important mechanism for miRNA deregulation in cancer. MiR-129-2 has been reported
      to be down-regulated and functions as a tumor suppressor in a few human cancers.
      However, the involvement of miR-129-2 in the pathology of glioma and the
      mechanism underlying miR-129-2 regulation in glioma cells remain unclear. In this
      study, we performed quantitative PCR to investigate the level of miR-129-2 in 21
      pairs of glioma tumors and matched adjacent tissues and found that miR-129-2 is
      down-regulated in glioma tumors. In vitro cell growth, apoptosis, cell migration,
      and invasion assays revealed that miR-129-2 functions as a tumor suppressor in
      glioma cells. Luciferase reporter assay found that miR-129-2 could directly
      target high-mobility group box 1 (HMGB1) and inhibit its expression in glioma
      cells. Methylation-specific PCR found that DNA methylation in upstream regions of
      miR-129-2 occured more frequently in cancer tissues than in adjacent tissues.
      Demethylation of miR-129-2 by 5-aza-2'-deoxycytidine treatment and quantitative
      PCR analysis revealed that miR-129-2 expression is epigenetically regulated in
      glioma cells. Taken together, our data suggested that miR-129-2 functions as a
      tumor suppressor in glioma cells by directly targeting HMGB1 and is down
      regulated by DNA methylation, which may provide a novel therapeutic strategy for
      treatment of glioma.

PMID- 25772486
TI  - Overexpression of HMGA1 correlates with the malignant status and prognosis of
      breast cancer.
AB  - High mobility group A1 (HMGA1), as a major member of HMGA family, plays an
      important part in promotion of cell proliferation and motility, induction of
      epithelial-mesenchymal transition, and maintenance of stemness, but little is
      known about the pathological role of HMGA1 in breast cancer patients. The aim of
      this study was to identify the pathological roles of HMGA1 in breast cancer. In
      our results, we found that mRNA and protein expression levels of HMGA1 were
      markedly higher in breast cancer tissues than in normal breast tissues. Using
      immunohistochemistry, high levels of HMGA1 protein were positively correlated
      with the status of histological grade (I-II vs. III-IV; P = 0.023), clinical
      stage (I-II vs. III-IV; P = 0.008), tumor size (T1-T2 vs. T3-T4; P = 0.015),
      lymph node metastasis (N0-N1 vs. N2-N3; P = 0.002), distant metastasis (M0 vs.
      M1; P < 0.001), and triple-negative breast cancer (No vs. Yes; P = 0.014) of
      breast cancer patients. Patients with higher HMGA1 expression had a significantly
      shorter overall survival time than did patients with low HMGA1 expression.
      Multivariate analysis indicated that the level of HMGA1 expression was an
      independent prognostic indicator (P < 0.001) for the survival of patients with
      breast cancer. In conclusion, HMGA1 plays an important role on breast cancer
      aggressiveness and prognosis and may act as a promising target for prognostic
      prediction.

PMID- 25772487
TI  - Donor-derived HTLV-1 associated myelopathy after transplantation: a call for
      targeted screening.

PMID- 25772488
TI  - Gender Dissimilarity in Type 2 Diabetes Risk Factors: a Chinese Study.
AB  - BACKGROUND: Gender has been identified as a significant factor that contributes
      to variations on unhealthy behavior engagement and disparity in health outcomes;
      however, gender dissimilarity in type 2 diabetes-related behavioral risks has not
      been fully understood in a non-Western social setting. PURPOSES: Recognizing
      gender-specific behavioral risks of type 2 diabetes is important in improving the
      disease associated health outcomes and healthcare service. This study identifies
      gender-specific behavioral factors associated with type 2 diabetes diagnoses
      among middle-aged and older adults in a Chinese context.  METHODS: Data are
      selected from the China Health and Nutrition Survey (CHNS) 2009. There are 259
      male cases and 280 female cases individually matched with their nondiabetic
      controls on age. RESULTS: Higher level of total carbohydrate intake and physical
      inactivity is associated with a higher risk of type 2 diabetes diagnoses in both
      genders (p < .001). Odds ratios of type 2 diabetes diagnoses are higher only
      among male cigarette smokers and heavy alcohol drinkers. CONCLUSIONS: This study
      provides evidence regarding gender-specific behavioral risks of type 2 diabetes
      suggesting the need for improving type 2 diabetes related research, prevention,
      education, and healthcare services for middle-aged and older adults in China.

PMID- 25772489
TI  - Dose-response and histopathological study, with special attention to the
      hypophysis, of the differential effects of domoic acid on rats and mice.
AB  - The effects of the neurotoxin domoic acid (DA) in the central nervous system of
      rodents (essentially rats and mice) after intraperitoneal administration have
      been profusely studied in the past. These observations have shown that the toxin
      induces similar symptoms and pathology in both species, but the lethality varies
      greatly. This article addresses the common and specific histopathological effects
      in rats and mice and the difference in sensitivity of these species to DA.
      Various sublethal and lethal doses were employed in mice (from 3 mg/kg to 8
      mg/kg) to observe their neurotoxicity by using different histological techniques,
      and these results were compared with the pathological effects after the
      administration of LD50 in rats (2.5 mg/kg). Additionally we also detected the
      presence of this toxin in various tissues by means of immunohistochemistry. Our
      results showed that rats are more vulnerable than mice to the neurotoxic effects
      of DA after intraperitoneal inoculation: lethality was extremely high in rats and
      the toxin produced hippocampal damage in rats surviving the intoxication, while
      lesions were not observed in DA-inoculated mice. As for similarities between rats
      and mice, both displayed similar clinical signs and in both the toxin was
      detected in the hypophysis by immunohistochemistry, a brain region not reported
      to date as target of the toxin.

PMID- 25772490
TI  - Identification of Covalent Bromodomain Binders through DNA Display of Small
      Molecules.
AB  - The regulation of transcriptional programs by epigenetic readers (bromodomains)
      has been linked to the development of several pathologies. Notably, it has been
      implicated in the regulation of cellular growth and evasion of apoptosis, in
      cancer as well as in inflammation. The discovery of small-molecule probes to
      dissect the role of bromodomains is thus important. We demonstrate that specific
      cysteine residues conserved across the bromodomains can be harnessed for covalent
      trapping. We report the discovery of two small molecules that form a covalent
      bond with cysteine residues conserved across the bromodomain family, analyze the
      subset of bromodomains that can be addressed through covalent binding, and show
      proteomic analyses enabled by the enrichment of bromodomains from native lysates.

PMID- 25772491
TI  - Intermediate and Long-term Outcomes of Giant Fibroadenoma Excision in Adolescent
      and Young Adult Patients.
AB  - Giant fibroadenomas (5 cm or greater) are benign breast masses that often present
      in adolescence and require surgical excision. Long-term outcomes, recurrence
      rates, and the need for additional reconstructive surgery in this population are
      unknown. Patients aged 11-25 years whose pathology reports indicated the presence
      of a giant fibroadenoma were eligible for this study. Medical records were
      reviewed for presentation, treatment, and outcomes. A subset of patients
      completed an investigator-designed long-term outcome survey to measure additional
      outcomes and the desire or need for subsequent reconstructive surgery. Forty-six
      patients with at least one giant fibroadenoma (mean size 7.4 +/- 2.8 cm) were
      identified. Most patients underwent excision with a periaroeolar incision (n =
      31), and an enucleation technique (n = 41), and four patients underwent immediate
      breast reconstruction. Thirty-three patients had complete medical records with a
      mean follow-up time of 2.2 +/- 4.1 years and no complaints of asymmetry,
      additional breast deformities, or reconstructive surgery procedures documented.
      In addition, nine patients completed the investigator-designed survey with a mean
      follow-up time of 10.1 +/- 8.7 years (range 1.5-27.0). Three of these patients
      reported postoperative breast asymmetry and the desire to pursue reconstructive
      surgery. Aesthetic outcomes of giant fibroadenoma excision may be satisfactory
      for many patients without immediate reconstruction, but for others, the need for
      reconstructive surgery may arise during development. Providers should address
      this potential need prior to discussing treatment options and during
      postoperative follow-up. Caution should be exercised before recommending
      immediate reconstruction.

PMID- 25772492
TI  - Automated neuromelanin imaging as a diagnostic biomarker for Parkinson's disease.
AB  - BACKGROUND: We aimed to analyze the diagnostic accuracy of an automated
      segmentation and quantification method of the SNc and locus coeruleus (LC)
      volumes based on neuromelanin (NM)-sensitive MRI (NM-MRI) in patients with
      idiopathic (iPD) and monogenic (iPD) Parkinson's disease (PD). METHODS: Thirty
      six patients (23 idiopathic and 13 monogenic PARKIN or LRRK2 mutations) and 37
      age-matched healthy controls underwent 3T-NM-MRI. SNc and LC volumetry were
      performed using fully automated multi-image atlas segmentation. The diagnostic
      performance to differentiate PD from controls was measured using the area under
      the curve (AUC) and likelihood ratios based on receiver operating characteristic
      (ROC) analyses. RESULTS: We found a significant reduction of SNc and LC volumes
      in patients, when compared to controls. ROC analysis showed better diagnostic
      accuracy when using SNc volume than LC volume. Significant differences between
      ipsilateral and contralateral SNc volumes, in relation to the more clinically
      affected side, were found in patients with iPD (P = 0.007). Contralateral atrophy
      in the SNc showed the highest power to discriminate PD subjects from controls
      (AUC, 0.93-0.94; sensitivity, 91%-92%; specificity, 89%; positive likelihood
      ratio: 8.4-8.5; negative likelihood ratio: 0.09-0.1 at a single cut-off point).
      Interval likelihood ratios for contralateral SNc volume improved the diagnostic
      accuracy of volumetric measurements. CONCLUSION: SNc and LC volumetry based on NM
      MRI resulting from the automated segmentation and quantification technique can
      yield high diagnostic accuracy for differentiating PD from health and might be an
      unbiased disease biomarker. (c) 2015 International Parkinson and Movement
      Disorder Society.

PMID- 25772493
TI  - Enhancer-promoter interaction facilitated by transiently forming G-quadruplexes.
AB  - G-quadruplexes are guanine-rich nucleic acid sequences capable of forming a four
      stranded structure through Hoogsteen hydrogen bonding. G-quadruplexes are highly
      concentrated near promoters and transcription start sites suggesting a role in
      gene regulation. They are less often found on the template than non-template
      strand where they either inhibit or enhance transcription, respectively. However,
      their potential role in enhancers and other distal regulatory elements has not
      been assessed yet. Here we show that DNAse hypersensitive (DHS) cis-regulatory
      elements are also enriched in Gs and their G-content correlate with that of their
      respective promoters. Besides local G4s, the distal cis regions may form G
      quadruplexes together with the promoters, each contributing half a G4. This model
      is supported more for the non-template strand and we hypothesised that the G4
      forming capability of the promoter and the enhancer non-template strand could
      facilitate their binding together and making the DHS regions accessible for the
      transcription factory. 

PMID- 25772495
TI  - A detailed analysis of the mechanism of a carbocationic triple shift
      rearrangement.
AB  - The mechanism of a carbocationic triple shift rearrangement is analyzed within
      the conceptual framework of the reaction force. All the systems were
      characterized computationally using DFT through B3LYP/6-31+G(d,p) methodology. A
      complete description of the electronic activity taking place during the reaction
      emerged through the use of the reaction electronic flux that, together with an
      NBO Wiberg bond order, produces a detailed picture of the reaction mechanism in
      terms of chemical events that drive the reaction during the different stages of
      the process. It is found that a carbocation triple shift occurs asynchronously
      although in a concerted way. 

PMID- 25772494
TI  - Bimolecular Fluorescence Complementation (BiFC) Analysis: Advances and Recent
      Applications for Genome-Wide Interaction Studies.
AB  - Complex protein networks are involved in nearly all cellular processes. To
      uncover these vast networks of protein interactions, various high-throughput
      screening technologies have been developed. Over the last decade, bimolecular
      fluorescence complementation (BiFC) assay has been widely used to detect protein
      protein interactions (PPIs) in living cells. This technique is based on the
      reconstitution of a fluorescent protein in vivo. Easy quantification of the BiFC
      signals allows effective cell-based high-throughput screenings for protein
      binding partners and drugs that modulate PPIs. Recently, with the development of
      large screening libraries, BiFC has been effectively applied for genome-wide PPI
      studies and has uncovered novel protein interactions, providing new insight into
      protein functions. In this review, we describe the development of reagents and
      methods used for BiFC-based screens in yeast, plants, and mammalian cells. We
      also discuss the advantages and drawbacks of these methods and highlight the
      application of BiFC in large-scale studies. 

PMID- 25772496
TI  - A gecko skin micro/nano structure - A low adhesion, superhydrophobic, anti
      wetting, self-cleaning, biocompatible, antibacterial surface.
AB  - Geckos, and specifically their feet, have attracted significant attention in
      recent times with the focus centred around their remarkable adhesional
      properties. Little attention however has been dedicated to the other remaining
      regions of the lizard body. In this paper we present preliminary investigations
      into a number of notable interfacial properties of the gecko skin focusing on
      solid and aqueous interactions. We show that the skin of the box-patterned gecko
      (Lucasium sp.) consists of dome shaped scales arranged in a hexagonal patterning.
      The scales comprise of spinules (hairs), from several hundred nanometres to
      several microns in length, with a sub-micron spacing and a small radius of
      curvature typically from 10 to 20 nm. This micro and nano structure of the skin
      exhibited ultralow adhesion with contaminating particles. The topography also
      provides a superhydrophobic, anti-wetting barrier which can self clean by the
      action of low velocity rolling or impacting droplets of various size ranges from
      microns to several millimetres. Water droplets which are sufficiently small (10
      100 MUm) can easily access valleys between the scales for efficient self-cleaning
      and due to their dimensions can self-propel off the surface enhancing their
      mobility and cleaning effect. In addition, we demonstrate that the gecko skin has
      an antibacterial action where Gram-negative bacteria (Porphyromonas gingivalis)
      are killed when exposed to the surface however eukaryotic cell compatibility
      (with human stem cells) is demonstrated. The multifunctional features of the
      gecko skin provide a potential natural template for man-made applications where
      specific control of liquid, solid and biological contacts is required.

PMID- 25772497
TI  - Super-hydrophobic multi-walled carbon nanotube coatings for stainless steel.
AB  - We have taken advantage of the native surface roughness and the iron content of
      AISI 316 stainless steel to directly grow multi-walled carbon nanotube (MWCNT)
      random networks by chemical vapor deposition (CVD) at low-temperature (1000
      degrees C) without the addition of any external catalysts or time-consuming pre
      treatments. In this way, super-hydrophobic MWCNT films on stainless steel sheets
      were obtained, exhibiting high contact angle values (154 degrees C) and high
      adhesion force (high contact angle hysteresis). Furthermore, the investigation of
      MWCNT films with scanning electron microscopy (SEM) reveals a two-fold
      hierarchical morphology of the MWCNT random networks made of hydrophilic
      carbonaceous nanostructures on the tip of hydrophobic MWCNTs. Owing to the
      Salvinia effect, the hydrophobic and hydrophilic composite surface of the MWCNT
      films supplies a stationary super-hydrophobic coating for conductive stainless
      steel. This biomimetical inspired surface not only may prevent corrosion and
      fouling, but also could provide low friction and drag reduction.

PMID- 25772498
TI  - Sediment prokaryote communities in different sites of eutrophic Lake Taihu and
      their interactions with environmental factors.
AB  - To investigate the temporal variation of the sediment prokaryote communities and
      their relation with the rapid increase of algae population in Taihu, a shallow
      eutrophic freshwater Lake, water and surface sediments were sampled from seven
      sites in different stages of algal bloom. The physicochemical characterization
      revealed positive correlations among the nutrient (N, P) parameters in the water
      and sediments, as well as TN/TP ratio 30.79 in average in water and 0.13 in
      sediments, demonstrating that P content was the limit factor for bloom in Taihu
      and sediment was an important nutrient resource for the water body. T-RFLP
      analysis of 16S rRNA genes revealed a diversity decrease of sediment prokaryotic
      communities along the bloom. The bacterial communities in sediments were more
      sensitive and shaped by the temporal changes, while archaea were more sensitive
      to the trophic level. The pyrosequencing data showed clear spatial and temporal
      changes in diversity of sediment bacteria. Betaproteobacteria was the most
      abundant group in all the samples, following by Delta-, Gama- and Alpha
      proteobacteria, Acidobacteria, Chlorobi, Chloroflexi etc. At the genus level,
      Thiobacillus and Sulfuricurvum were the most dominant groups in the sediments,
      and the increase of Thiobacillus abundance in February might be used as
      bioindicator for the subsequent bloom. In addition, NO3 (-)-N was evidenced to be
      the main factor to regulate the bacterial community structure in the sediments.
      These results offered some novel and important data for the evaluation and
      predict the algal bloom in Taihu and can be reference for other shallow fresh
      water lakes. 

PMID- 25772499
TI  - Experimental verification of a conserved intronic microRNA located in the human
      TrkC gene with a cell type-dependent apoptotic function.
AB  - Tropomyosin receptor kinase C (TrkC) is involved in cell survival, apoptosis
      induction and tumorigenesis. We hypothesized that, similar to p75(NTR) receptor,
      some of the diverse functions of TrkC could be mediated by a microRNA (miRNA)
      embedded within the gene. Here, we experimentally verified the expression and
      processing of two bioinformatically predicted miRNAs named TrkC-miR1-5p and TrkC
      miR1-3p. Transfecting a DNA fragment corresponding to the TrkC-premir1 sequence
      in HEK293t cells caused ~300-fold elevation in the level of mature TrkC-miR1 and
      also a significant downregulation of its predicted target genes. Furthermore,
      endogenous TrkC-miR1 was detected in several cell lines and brain tumors
      confirming its endogenous generation. Furthermore, its orthologous miRNA was
      detected in developing rat brain. Accordingly, TrkC-miR1 expression was increased
      during the course of neural differentiation of NT2 cell, whereas its suppression
      attenuated NT2 differentiation. Consistent with opposite functions of TrkC, TrkC
      miR1 overexpression promoted survival and apoptosis in U87 and HEK293t cell
      lines, respectively. In conclusion, our data report the discovery of a new miRNA
      with overlapping function to TrkC. 

PMID- 25772501
TI  - Role of SRC-like adaptor protein (SLAP) in immune and malignant cell signaling.
AB  - SRC-like adaptor protein (SLAP) is an adaptor protein structurally similar to the
      SRC family protein kinases. Like SRC, SLAP contains an SH3 domain followed by an
      SH2 domain but the kinase domain has been replaced by a unique C-terminal region.
      SLAP is expressed in a variety of cell types. Current studies suggest that it
      regulates signaling of various cell surface receptors including the B cell
      receptor, the T cell receptor, cytokine receptors and receptor tyrosine kinases
      which are important regulator of immune and cancer cell signaling. SLAP targets
      receptors, or its associated components, by recruiting the ubiquitin machinery
      and thereby destabilizing signaling. SLAP directs receptors to ubiquitination
      mediated degradation and controls receptors turnover as well as signaling. Thus,
      SLAP appears to be an important component in regulating signal transduction
      required for immune and malignant cells. 

PMID- 25772502
TI  - The profile of adult onset Henoch-Schonlein purpura in an Asian population.
AB  - BACKGROUND: Henoch-Schonlein purpura (HSP) is less common in adults and has been
      linked with a more severe clinical syndrome as well as a higher frequency of
      renal disease and internal malignancy. Renal involvement in adult HSP has been
      significantly associated with antecedent infections, pyrexia at time of first
      presentation, and purpura above the waist. We aim to evaluate the frequency of
      cutaneous and extra-cutaneous features and identify the predictive factors for
      renal involvement in Asian adults with HSP. METHODS: We performed a retrospective
      study of 48 adult Asian patients diagnosed with HSP based on the European League
      Against Rheumatism (EULAR) criteria at a tertiary hospital in Singapore between
      January 2000 and December 2011. RESULTS: The most common cutaneous manifestations
      were palpable purpura (73%), papules (31%), and petechiae (27%). Forty-percent
      had cutaneous lesions extending above the waist. Fifteen patients (31%) had
      gastrointestinal symptoms, 21 (44%) had joint involvement, and 27 (56%) had renal
      disease. Seventy-percent of patients with pyrexia at presentation experienced
      renal disease, whereas only 30% without pyrexia had renal involvement (P =
      0.018). Sixty-six percent of patients with purpura had renal involvement as
      compared to 31% in those without purpura (P = 0.049). The frequency of renal
      involvement in patients with purpura above the waist (52%) was similar to those
      with purpura below the waist (55%). CONCLUSIONS: Our study confirms that HSP in
      adults tends to be more severe with a high incidence of extracutaneous
      manifestations, especially renal disease. Pyrexia at presentation and the
      presence of purpura were significant predictive factors for renal involvement.

PMID- 25772503
TI  - Magnesium uptake of Arabidopsis transporters, AtMRS2-10 and AtMRS2-11, expressed
      in Escherichia coli mutants: Complementation and growth inhibition by aluminum.
AB  - Magnesium (Mg2+) plays a critical role in many physiological processes. Mg2+
      transport systems in Salmonella have been well documented, but those in
      Escherichia coli have not been fully elucidated. We examined the effects of corA,
      mgtA, yhiD and corC gene deletion on Mg2+ transport in E. coli. We obtained every
      combination of double, triple and quadruple mutants. The corA and mgtA double
      mutant required addition of 10 mM Mg2+ to Luria-Bertani (LB) medium for growth,
      and the corA, mgtA and yhiD triple mutant TM2 required a higher Mg2+
      concentration. The Mg2+ requirement of the quadruple mutant was similar to that
      of TM2. The results demonstrated that either CorA or MgtA is necessary for normal
      E. coli growth in LB medium and that YhiD plays a role in Mg2+ transport under
      high Mg2+ growth conditions in E. coli. The Arabidopsis Mg2+ transporters, AtMRS2
      10 and AtMRS2-11, were heterologously expressed in TM2 cells. TM2 cells
      expressing AtMRS2-10 and AtMRS2-11 could grow in LB medium that had been
      supplemented with 1 mM Mg2+ and without Mg2+ supplementation, respectively, and
      cell growth was inhibited by 2 mM AlCl3. The results indicated that the growth of
      TM2 expressing AtMRS2-10 and AtMRS2-11 reflected these AtMRS2 function for Mg2+
      and aluminum. The E. coli TM2 cells are useful for functional analysis of
      Arabidopsis MRS2 proteins.

PMID- 25772504
TI  - Genotype-specific differences in structural features of hepatitis C virus (HCV)
      p7 membrane protein.
AB  - The 63 amino acid polytopic membrane protein, p7, encoded by hepatitis C virus
      (HCV) is involved in the modulation of electrochemical gradients across membranes
      within infected cells. Structural information relating to p7 from multiple
      genotypes has been generated in silico (e.g. genotype (GT) 1a), as well as
      obtained from experiments in form of monomeric and hexameric structures (GTs 1b
      and 5a, respectively). However, sequence diversity and structural differences
      mean that comparison of their channel gating behaviour has not thus far been
      simulated. Here, a molecular model of the monomeric GT 1a protein is optimized
      and assembled into a hexameric bundle for comparison with both the 5a hexamer
      structure and another hexameric bundle generated using the GT 1b monomer
      structure. All bundles tend to turn into a compact structure during molecular
      dynamics (MD) simulations (Gromos96 (ffG45a3)) in hydrated lipid bilayers, as
      well as when simulated at 'low pH', which may trigger channel opening according
      to some functional studies. Both GT 1a and 1b channel models are gated via
      movement of the parallel aligned helices, yet the scenario for the GT 5a protein
      is more complex, with a short N-terminal helix being involved. However, all
      bundles display pulsatile dynamics identified by monitoring water dynamics within
      the pore. 

PMID- 25772505
TI  - Association of severe disc degeneration with all-cause mortality and abdominal
      aortic calcification assessed prospectively in older men: findings of a single
      center prospective study of osteoporosis in men.
AB  - OBJECTIVE: To assess the association of disc degeneration with all-cause
      mortality and with the severity and rate of progression of abdominal aortic
      calcification (AAC) in older men. METHODS: Men >50 years of age (n = 766)
      underwent lateral spine radiography and blood collection and were monitored
      prospectively. We assessed the association of disc degeneration with all-cause
      mortality (at 10 years), AAC severity (at baseline), and AAC progression (at 7.5
      years). RESULTS: After adjustment for confounders, including AAC, the total
      overall grade score for AAC predicted all-cause mortality (hazard ratio [HR] 1.20
      per SD increase [95% confidence interval (95% CI) 1.01-1.43]). The highest
      tertile of the total overall grade score was associated with higher mortality
      rates (39.3/1,000 person-years for a score of >8 versus 20.9/1,000 person-years
      for a score of 0-8; adjusted HR 1.47 [95% CI 1.05-2.06]). The odds of severe AAC
      (score of >5) increased with the total disc space narrowing score (adjusted HR
      1.44 per SD [95% CI 1.11-1.87]). The highest tertile of the total disc space
      narrowing score was associated with higher odds of severe AAC (adjusted HR 2.42
      versus the lowest tertile [95% CI 1.24-4.73]). The probability of long-term AAC
      stability decreased with an increasing total osteophyte score (adjusted HR 0.66
      per SD [95% CI 0.49-0.88]). The highest tertile of the total osteophyte score was
      associated with a lower probability of AAC stability (adjusted HR 0.35 versus the
      lowest tertile [95% CI 0.18-0.71]). CONCLUSION: Older men with severe disc
      degeneration have greater AAC severity, faster AAC progression, and higher all
      cause mortality rates.

PMID- 25772506
TI  - Do Sunscreens Eliminate the Risk of Melanoma?

PMID- 25772500
TI  - Generation and degradation of free asparagine-linked glycans.
AB  - Asparagine (N)-linked protein glycosylation, which takes place in the eukaryotic
      endoplasmic reticulum (ER), is important for protein folding, quality control and
      the intracellular trafficking of secretory and membrane proteins. It is known
      that, during N-glycosylation, considerable amounts of lipid-linked
      oligosaccharides (LLOs), the glycan donor substrates for N-glycosylation, are
      hydrolyzed to form free N-glycans (FNGs) by unidentified mechanisms. FNGs are
      also generated in the cytosol by the enzymatic deglycosylation of misfolded
      glycoproteins during ER-associated degradation. FNGs derived from LLOs and
      misfolded glycoproteins are eventually merged into one pool in the cytosol and
      the various glycan structures are processed to a near homogenous glycoform. This
      article summarizes the current state of our knowledge concerning the formation
      and catabolism of FNGs. 

PMID- 25772507
TI  - Simplified CLARITY for visualizing immunofluorescence labeling in the developing
      rat brain.
AB  - CLARITY is an innovative technological advance in which intact biological tissue
      is transformed into a "nanoporous hydrogel-hybridized form" (Chung et al. 2013;
      Chung and Deisseroth 2013) with markedly improved chemical and optical
      accessibility, permitting fluorescent visualization and extraction of high
      resolution structural data from mm-thick blocks of tissue. CLARITY affords an
      excellent but as yet unexploited opportunity to visualize the growth and
      maturation of phenotypically identified neurons and axonal processes in the
      developing brain. This brief report describes a moderately revised, simplified,
      and less expensive CLARITY protocol that effectively reveals the structure of
      chemically identified neurons in whole neonatal/juvenile rat brains and tissue
      slabs. Rats [postnatal day (P)0-24] were transcardially perfused with one of two
      fixative/hydrogel solutions, followed by hydrogel polymerization to generate
      brain hybrids. Whole brain hybrids or 2.0-mm-thick coronal slabs were passively
      cleared of lipid and then processed for dual immunofluorescence labeling,
      including labeling using tyramide signal amplification. After refractive index
      matching using 2,20-Thiodiethanol (60 % solution), a Leica confocal microscope
      equipped with a CLARITY objective was used to view the hypothalamus in whole
      brain hybrids or slabs. Collected image stacks revealed the distribution and
      three-dimensional structure of hypothalamic pro-oxyphysin (oxytocin)-,
      neuropeptide Y-, glucagon-like peptide-1-, and tyrosine hydroxylase
      immunopositive neurons and processes within large tissue volumes. Outstanding
      structural preservation and immunolabeling quality demonstrates the efficacy of
      this approach for interrogating chemically defined neural circuits as they
      develop in postnatal rodent brain.

PMID- 25772508
TI  - Ryanodine-mediated conversion of STP to LTP is lacking in synaptopodin-deficient
      mice.
AB  - In previous studies we and others have found that activation of ryanodine
      receptors (RyRs) facilitate expression of long-term potentiation (LTP) of
      reactivity to afferent stimulation in hippocampal slices, with a more pronounced
      action in the ventral hippocampus. We have also been able to link the involvement
      of synaptopodin (SP), an actin-binding protein, with neuronal plasticity via its
      interaction with RyRs. To test this link more directly, we have now compared the
      ability of ryanodine to convert short-term to LTP in hippocampal slices taken
      from normal and SP-knockout (SPKO) mice. Indeed, SPKO hippocampus expresses lower
      concentrations of RyRs and in slices of these mice ryanodine is unable to
      facilitate conversion of short-term to LTP. These observations link functionally
      SP with calcium stores.

PMID- 25772509
TI  - Cannabinoid receptor-interacting protein Crip1a modulates CB1 receptor signaling
      in mouse hippocampus.
AB  - The cannabinoid type 1 receptor (Cnr1, CB1R) mediates a plethora of physiological
      functions in the central nervous system as a presynaptic modulator of
      neurotransmitter release. The recently identified cannabinoid receptor
      interacting protein 1a (Cnrip1a, CRIP1a) binds to the C-terminal domain of CB1R,
      a region known to be important for receptor desensitization and internalization.
      Evidence that CRIP1a and CB1R interact in vivo has been reported, but the
      neuroanatomical distribution of CRIP1a is unknown. Moreover, while alterations of
      hippocampal CRIP1a levels following limbic seizures indicate a role in
      controlling excessive neuronal activity, the physiological function of CRIP1a in
      vivo has not been investigated. In this study, we analyzed the spatial
      distribution of CRIP1a in the hippocampus and examined CRIP1a as a potential
      modulator of CB1R signaling. We found that Cnrip1a mRNA is co-expressed with Cnr1
      mRNA in pyramidal neurons and interneurons of the hippocampal formation. CRIP1a
      protein profiles were largely segregated from CB1R profiles in mossy cell
      terminals but not in hippocampal CA1 region. CB1R activation induced
      relocalization to close proximity with CRIP1a. Adeno-associated virus-mediated
      overexpression of CRIP1a specifically in the hippocampus revealed that CRIP1a
      modulates CB1R activity by enhancing cannabinoid-induced G protein activation.
      CRIP1a overexpression extended the depression of excitatory currents by
      cannabinoids in pyramidal neurons of the hippocampus and diminished the severity
      of chemically induced acute epileptiform seizures. Collectively, our data
      indicate that CRIP1a enhances hippocampal CB1R signaling in vivo.

PMID- 25772510
TI  - The Relationship between Local Economic Conditions and Acute Myocardial
      Infarction Hospital Utilization by Adults and Seniors in the United States, 1995
      2011.
AB  - OBJECTIVE: To assess the association between aggregate unemployment and hospital
      discharges for acute myocardial infarction (AMI) among adults and seniors, 1995
      2011. DATA SOURCES/STUDY SETTING: Community hospital discharge data from states
      collected for the Healthcare Cost and Utilization Project (HCUP) State Inpatient
      Databases (SID) and economic data from the Bureau of Labor Statistics, 1995-2011.
      STUDY DESIGN: Quarterly time series study of unemployment and aggregate hospital
      discharges in local areas using fixed effects to control for differences between
      local areas. DATA COLLECTION/EXTRACTION METHODS: Secondary data on inpatient
      stays and unemployment rates aggregated to micropolitan and metropolitan areas.
      PRINCIPAL FINDINGS: For both adults and seniors, a 1 percentage point increase in
      the contemporaneous unemployment rate was associated with a statistically
      significant 0.80 percent (adults) to 0.96 percent (seniors) decline in AMI
      hospitalization during the first half of the study but was unrelated to the
      economic cycle in the second half of the study period. CONCLUSIONS: The study
      found evidence that the aggregate relationship between health and the economy may
      be shifting for cardiovascular events, paralleling recent research that has shown
      a similar shift for some types of mortality (Ruhm 2013), self-reported health,
      and inpatient use among seniors (McInerney and Mellor 2012).

PMID- 25772511
TI  - Neutrophil-guided dosing of anthracycline-cyclophosphamide-containing
      chemotherapy in patients with breast cancer: a feasibility study.
AB  - The aim of this study was to investigate whether neutrophil-guided dose
      escalation of anthracycline-cyclophosphamide-containing chemotherapy (ACC) for
      breast cancer is feasible, in order to optimize outcome. Breast cancer patients
      planned for 3-weekly ACC were enrolled in this study. The first treatment cycle
      was administered in a standard BSA-adjusted dose. The absolute neutrophil count
      was measured at baseline and at day 8, 11 and 15 after administration of ACC. For
      patients with none or mild (CTC grade 0-2) neutropenia and no other dose-limiting
      toxicity, we performed a 10-25 % dose escalation of the second cycle with the
      opportunity to a further 10-25 % dose escalation of the third cycle. Thirty
      patients were treated in the adjuvant setting with either FE100C (n = 23) or AC
      (n = 4), or in the palliative setting with FAC (n = 3). Two out of 23 patients (9
      %) treated with FEC did not develop grade 3-4 neutropenia after the first
      treatment cycle. Dose escalation was performed in these two patients (30 % in one
      and 15 % in the other patient). During dose escalation, there were no
      complications like febrile neutropenia. No patients treated with FAC or AC could
      be escalated, since all of them developed grade 3-4 neutropenia. We conclude that
      asymptomatic grade 3-4 neutropenia is likely to be achieved in the majority of
      patients with breast cancer treated with ACC according to presently advocated BSA
      based dose levels. Escalation of currently advocated ACC doses without G-CSF,
      with a target of grade 3-4 neutropenia, is feasible, but only possible in a small
      proportion of patients. EudraCT 2010-020309-33. 

PMID- 25772512
TI  - Comprehensive geriatric assessment and traditional Chinese medicine intervention
      benefit symptom control in elderly patients with advanced non-small cell lung
      cancer.
AB  - The aim of this study was to observe the symptom improvement and clinical benefit
      in elderly patients with advanced non-small cell lung cancer (NSCLC) stratified
      on the basis of CGA findings after treatment with a combination of traditional
      Chinese medicine and Western medicine. Twenty-four elderly advanced NSCLC
      patients with a mean age of 73.0 +/- 5.3 (65-83) years were categorized into
      three stratifications according to CGA results, namely function independent,
      mildly function impaired, and function dependent. They received standardized
      therapy, individualized therapy, and best supportive care, respectively. The
      patients receiving standardized therapy and individualized therapy were
      randomized into two groups, with or without traditional Chinese medicine for
      symptom control, while for all the patients receiving best supportive care,
      traditional Chinese medicine was administered. Nine non-elderly NSCLC patients
      (<65 years old) were enrolled as control and treated in accordance with NCCN
      NSCLC treatment guidelines. EORTC QLQ-C30 core scale, LC13 scale, and MDASI-TCM
      scale were used to assess relevant symptoms before and after treatment. After
      treatment for 3 weeks, it was shown by QLQ-C30+LC13 scales, for function
      dependent patients, that the physical and role performances and the global health
      status were improved and the symptoms of fatigue and cough were alleviated; by
      MDASI-TCM scale, the symptoms of fatigue, cough, and expectoration were improved.
      In function-independent and mildly function-impaired elderly patients, there were
      no significant changes in functional status and symptoms. But in non-elderly
      patients, the physical and social performances were lowered, and the symptoms of
      fatigue, constipation, and poor appetite were aggravated. The elderly patients
      with advanced NSCLC were categorized on the basis of CGA findings, and
      traditional Chinese medicine may be beneficial to symptom control of function
      dependent patients.

PMID- 25772513
TI  - In search of the optimal rapid response system bundle.

PMID- 25772514
TI  - Bioisosteric matrices for ligands of serotonin receptors.
AB  - The concept of bioisosteric replacement matrices is applied to explore the
      chemical space of serotonin receptor ligands, aiming to determine the most
      efficient ways of manipulating the affinity for all 5-HT receptor subtypes.
      Analysis of a collection of over 1 million bioisosteres of compounds with
      measured activity towards serotonin receptors revealed that an average of 31 % of
      the ligands for each target are mutual bioisosteres. In addition, the collected
      dataset allowed the development of bioisosteric matrices-qualitative and
      quantitative descriptions of the biological effects of each predefined type of
      bioisosteric substitution, providing favored paths of modifying the compounds.
      The concept exemplified here for serotonin receptor ligands can likely be more
      broadly applied to other target classes, thus representing a useful guide for
      medicinal chemists designing novel ligands.

PMID- 25772515
TI  - Self-disinfecting sink drains reduce the Pseudomonas aeruginosa bioburden in a
      neonatal intensive care unit.
AB  - AIM: Water in sink drains is a known source of gram-negative bacteria. We aimed
      to evaluate the impact of self-disinfecting sink drains on the emission of
      aerosolised bacteria and on Pseudomonas aeruginosa acquisition among neonates.
      METHODS: Aerosol bacterial growth and patient Pseudomonas aeruginosa acquisition
      rates were measured at baseline (Phase One), for 13 months after sinks were
      relocated or redesigned during refurbishment (Phase Two) and for 13 months after
      introducing self-disinfecting sink drains (Phase Three). RESULTS: Cultures were
      positive for bacterial growth in 56%, 24% and 13% of the tested aerosols in
      Phases One, Two and Three, respectively. Comparing Phases Two and Three produced
      an odds ratio (OR) of 0.47, with a 95% confidence interval (CI) of 0.22-0.99 (p =
      0.047), for all bacteria and an OR of 0.31 and CI of 0.12-0.79 (p = 0.013) for
      Pseudomonas aeruginosa. Rates of Pseudomonas aeruginosa positive clinical
      cultures were 0.34, 0.27 and 0.13 per 1000 patient days during the respective
      phases, with a significant increase of time to the next positive clinical culture
      in Phase Three. CONCLUSION: Self-disinfecting sink drains were superior to sink
      replacements in preventing emissions from aerosols pathogens and may reduce
      hospital-acquired infections. The bioburden reduction should be confirmed in a
      larger multicentre trial.

PMID- 25772516
TI  - Relatives of patients with amyotrophic lateral sclerosis: Their experience of
      care and support.
AB  - OBJECTIVE: The purpose of this study was to describe relatives' experience of
      patient care and the support they themselves received during the course of
      disease progression. METHOD: A total of 15 relatives were included from two
      neurology clinics in Sweden: 7 wives, 4 husbands, and 4 daughters. Data were
      collected through qualitative interviews 6 to 12 months after the patient had
      died. Content analysis was performed to analyze the interviews. RESULT: The
      results showed that patient care was experienced as positive and as being based
      on the patient's needs and desires. Treatment from the staff, support and help,
      knowledge, availability, and continuity among the team were important reasons for
      the relations to feel secure. In addition, support for relatives was available,
      but different factors influenced its use. Most relatives did not think about
      their own needs but focused on the patient. SIGNIFICANCE OF RESULTS: It is
      important that care and support for both patients and relatives be based on
      individual needs. The staff members responsible for providing this care and
      support must have knowledge and experience of the disease and its specific care.
      If they do not belong to an ALS (amyotrophic lateral sclerosis) team, they may
      require further education and support. The relatives focus on the patient's
      situation and do not think of their own needs. It is therefore important that
      health professionals be observant of the relatives and offer them help and
      support to better manage their situation.

PMID- 25772517
TI  - Morphological study of the occipital belly of the occipitofrontalis muscle and
      its innervation.
AB  - PURPOSE: Occipital belly (OB) of occipitofrontalis muscle (epicranius) is a
      muscle which covers the occipital part of the skull. The posterior auricular
      nerve (PAN) is the first extracranial branch of the facial nerve, which supplies
      the OB. The PAN is one of the structures used to identify the facial nerve during
      surgeries such as parotidectomy and mastoidectomy. In the present report, we
      provide detailed anatomical knowledge of the OB and its innervation. METHODS:
      Twenty-six hemifaces from 14 Korean cadavers were dissected. The mastoid tip,
      external occipital protuberance (EOP), a horizontal line that is parallel to the
      Frankfurt horizontal plane (x-axis), and a vertical line through the EOP (y-axis)
      were used as reference points and lines. RESULTS: The OB demonstrated a variety
      of features and was mostly asymmetrical. The muscle bellies were observed to
      angle toward the temporoparietalis muscle laterally, with the aponeurosis angled
      at approximately 55 degrees -65 degrees . The mean width and height were 60.9 +/-
      8.7 and 31.7 +/- 7.5 mm, respectively. Muscle bellies were located at a mean
      distance of 7.1 +/- 2.5 mm superior to the x-axis and 29.6 +/- 6.4 mm lateral to
      the y-axis. The mean vertical distance from the origin of the PAN at the anterior
      border of the mastoid process (MP) to the mastoid tip was 6.1 +/- 2.1 mm. The
      mean nerve angle between the PAN and the x-axis was 55.7 degrees  +/- 6.8 degrees
      . The entry point of the PAN that innervates the OB was positioned at a mean
      distance of 9.0 +/- 3.5 mm superior to the x-axis and 79.0 +/- 8.1 mm lateral to
      the y-axis. CONCLUSIONS: Understanding the morphometrical characteristics of the
      OB and its innervation may potentially improve surgical outcomes to assist in
      locating the posterior auricular branch of the facial nerve.

PMID- 25772519
TI  - Gas-phase kinetics of the N + C2N reaction at low temperature.
AB  - The rate of the gas-phase N((4)S) + C2N(X(2)Pii) reaction has been measured in a
      continuous supersonic flow reactor down to 54 K through the relative-rate method
      using the N((4)S) + OH(X(2)Pi) -> H((2)S) + NO(X(2)Pi) reaction as a reference.
      The microwave discharge technique was employed to produce high concentrations of
      atomic nitrogen. Pulsed laser photolysis of precursor molecules Cl3C2N and H2O2
      at 212 nm in situ led to C2N and OH radical formation, respectively. The rate
      constant is shown to be approximately independent of temperature, in contrast to
      previous studies of atom-radical reactions involving atomic nitrogen. While the
      reaction rate is faster than previously estimated, astrochemical simulations
      indicate that this reaction is probably only a minor source of CN radicals in
      dense interstellar clouds.

PMID- 25772518
TI  - Anatomical correlation between existence of concha bullosa and maxillary sinus
      volume.
AB  - PURPOSE: The objective of this study was to assess the effects of concha bullosa
      variation on maxillary sinus volume and uncinate angle. METHOD: The study group
      included 169 patients (338 sides) who underwent either surgical or medical
      treatment with the diagnosis of chronic rhinosinusitis. The paranasal sinus
      computed tomography of these patients was analyzed to measure maxillary sinus
      volume, uncinate angle and existence of concha bullosa. Subsequently, these
      variables were evaluated to find out possible relationship inbetween. RESULTS:
      Mean maxillary sinus volume and uncinate angle at right and left sides were 15.21
      +/- 0.47 and 15.51 +/- 0.48 mm(3), 30.57 +/- 0.62 degrees  and 30.20 +/- 0.68
      degrees , respectively. There was no difference between patients with or without
      concha bullosa in regard to maxillary sinus volume and uncinate angle at both
      sides. Maxillary sinus volume and degree of uncinate angle did not show any
      significant correlation at both sides; r = -0.124, p = 0.107 and r = -0.136, p =
      0.078. CONCLUSION: In conclusion, concha bullosa is a common anatomical variation
      at nasal cavity. The existence of concha bullosa does not have any association
      with the volume of maxillary sinus and angle of uncinate process.

PMID- 25772520
TI  - Prospective study of topical 5-aminolevulinic acid photodynamic therapy for the
      treatment of severe adolescent acne in Chinese patients.
AB  - Acne vulgaris is one of the most common skin diseases in adolescents. In the
      present study, we aimed to evaluate the effectiveness and safety of topical 5
      aminolevulinic acid (ALA)-mediated photodynamic therapy (PDT) for the treatment
      of severe acne in Chinese adolescent patients. Twenty-one Chinese adolescent
      patients aged 12-18 years with Pillsbury III-IV severe facial acne were treated
      with three courses of ALA-PDT. A 5% ALA lotion was applied topically for 60 min
      followed by irradiation with light-emitting diode light at 633 nm with a light
      intensity of 75-80 mW/cm(2) and a light dose of 90-96 J/cm(2) . Clinical
      assessment was conducted before and after each treatment, and at each follow-up
      session. The total effective rates were 85.71%, 90.48%, and 95.23% after the
      three PDT sessions, and at the 4- and 8-week follow ups, respectively. ALA-PDT is
      an effective treatment for severe adolescent acne vulgaris, and is associated
      with mild and reversible side-effects. 

PMID- 25772521
TI  - Broader prevalence of Wolbachia in insects including potential human disease
      vectors.
AB  - Wolbachia are intracellular, maternally transmitted bacteria considered the most
      abundant endosymbionts found in arthropods. They reproductively manipulate their
      host in order to increase their chances of being transmitted to the offspring,
      and currently are being used as a tool to control vector-borne diseases. Studies
      on distribution of Wolbachia among its arthropod hosts are important both for
      better understanding why this bacterium is so common, as well as for its
      potential use as a biological control agent. Here, we studied the incidence of
      Wolbachia in a broad range of insect species, collected from different regions of
      Brazil, using three genetic markers (16S rRNA, wsp and ftsZ), which varied in
      terms of their sensitivity to detect this bacterium. The overall incidence of
      Wolbachia among species belonging to 58 families and 14 orders was 61.9%. The
      most common positive insect orders were Coleoptera, Diptera, Hemiptera and
      Hymenoptera, with Diptera and Hemiptera having the highest numbers of Wolbachia
      positive families. They included potential human disease vectors whose infection
      status has never been reported before. Our study further shows the importance of
      using quantitative polymerase chain reaction for high-throughput and sensitive
      Wolbachia screening. 

PMID- 25772530
TI  - Enzootic bovine leukosis: report of eradication and surveillance measures in
      Italy over an 8-year period (2005-2012).
AB  - Bovine leukaemia virus (BLV) is associated with enzootic bovine leukosis (EBL).
      BLV causes malignant lymphoma and lymphosarcoma; however, most BLV infections
      remain clinically silent in an aleukaemic state. EBL is a notifiable disease, and
      official control measures include screening or monitoring, precautions at
      borders, control of movement inside the country, and stamping out. The objective
      of this study was to evaluate EBL eradication and surveillance measures in Italy
      from 2005 to 2012. One-hundred twenty-three outbreaks were recorded (1 January
      2006 to 31 December 2012) in the National Veterinary Information System (SIMAN)
      on 7 November 2013. Of these, 101 had occurred in southern Italy. An outbreak
      usually lasted for a few days, but sometimes lasted for weeks. Some areas were
      subjected to normal eradication measures, whereas others were subjected to
      additional eradication measures as a consequence of persisting EBL outbreaks.
      During the study period, we noted an overall annual decrease from 0.21% in 2005
      to 0.08% in 2012 in the herd prevalence rate, from 0.06% in 2005 to 0.04% in 2012
      in the herd incidence rate, and from 0.027% in 2005 to 0.015% in 2012 in the
      animal prevalence rate. Regions officially recognised as EBL-free areas were
      found to have their own surveillance plans. Differences in their surveillance
      plans include the type of sample (serum, milk, or both), age at which the animals
      must be tested (12 or 24 months), and test frequency of herds (annually or every
      2, 3, 4, 5, or 6 years). The eradication programme for EBL is difficult to
      implement in some Italian areas because of several factors such as incomplete
      herd registry, geographical location and socio-economic conditions of the region.

PMID- 25772522
TI  - A New Electrocardiographic Marker of Hypertensive Cardiac Damage.

PMID- 25772527
TI  - Clinical Management of Antipsychotic-Induced Hyperprolactinemia.
AB  - PURPOSE: This article describes the physiology and mechanisms of prolactin and
      the assessment and clinical management strategies of antipsychotic-induced
      hyperprolactinemia. CONCLUSIONS: Hyperprolactinemia is a disorder of the
      hypothalamic-pituitary axis which can be caused by several mechanisms. Typical
      antipsychotic agents are more likely to cause hyperprolactinemia than atypical
      antipsychotic agents, with the exception of amisulpride, paliperidone, and
      risperidone. PRACTICE IMPLICATIONS: Switching from prolactin-elevating to
      prolactin-sparing agents is recommended. Providing adjunctive treatment and
      prescribing substitutive hormones are alternatives. Education and lifestyle
      modification should be a major health promotion strategy. Taking patients'
      history and conducting physical examinations should be done during follow-up.

PMID- 25772535
TI  - Rotationally resolved state-to-state photoionization and the photoelectron study
      of vanadium monocarbide and its cations (VC/VC(+)).
AB  - By employing two-color visible (VIS)-ultraviolet (UV) laser photoionization and
      pulsed field ionization-photoelectron (PFI-PE) techniques, we have obtained
      highly rotationally resolved photoelectron spectra for vanadium monocarbide
      cations (VC(+)). The state-to-state VIS-UV-PFI-PE spectra thus obtained allow
      unambiguous assignments for the photoionization rotational transitions, resulting
      in a highly precise value for the adiabatic ionization energy (IE) of vanadium
      monocarbide (VC), IE(VC) = 57512.0 +/- 0.8 cm(-1) (7.13058 +/- 0.00010 eV), which
      is defined as the energy of the VC(+)(X(3)Delta1; v(+) = 0; J(+) = 1) <-
      VC(X(2)Delta3/2; v'' = 0; J'' = 3/2) photoionization transition. The
      spectroscopic constants for VC(+)(X(3)Delta1) determined in the present study
      include the harmonic vibrational frequency omegae(+) = 896.4 +/- 0.8 cm(-1), the
      anharmonicity constant omegae(+)xe(+) = 5.7 +/- 0.8 cm(-1), the rotational
      constants Be(+) = 0.6338 +/- 0.0025 cm(-1) and alphae(+) = 0.0033 +/- 0.0007 cm(
      1), the equilibrium bond length re(+) = 1.6549 +/- 0.0003 A, and the spin-orbit
      coupling constant A = 75.2 +/- 0.8 cm(-1) for VC(+)(X(3)Delta1,2,3). These highly
      precise energetic and spectroscopic data are used to benchmark state-of-the-art
      CCSDTQ/CBS calculations. In general, good agreement is found between the
      theoretical predictions and experimental results. The theoretical calculations
      yield the values, IE(VC) = 7.126 eV; the 0 K bond dissociation energies: D0(V-C)
      = 4.023 eV and D0(V(+)-C) = 3.663 eV; and heats of formation: DeltaH degrees
      (f0)(VC) = 835.2, DeltaH degrees (f298)(VC) = 840.4, DeltaH degrees (f0)(VC(+)) =
      1522.8, and DeltaH degrees (f298)(VC(+)) = 1528.0 kJ mol(-1).

PMID- 25772533
TI  - The Healthy Lifestyle Team is Central to the Success of Accountable Care
      Organizations.

PMID- 25772531
TI  - Extra-mammary findings on breast MRI: a pictorial review.
AB  - Recent improvements in breast coil performance have made detection of extra
      mammary findings increasingly common. Some of these findings have important
      clinical implications. The radiologist should be aware of the spectrum of extra
      mammary pathologies found on breast magnetic resonance imaging (MRI) and be able
      to distinguish clinically significant findings from those that are
      inconsequential. The purpose of this essay is to demonstrate various common and
      uncommon extra-mammary findings encountered while interpreting breast MRI and to
      detail appropriate management recommendations. 

PMID- 25772534
TI  - Cooperativity between individual transporter protomers: new data fuelling old
      complexes.
AB  - Neurotransmitter transporters are arranged in an oligomeric quaternary structure
      as evidenced by crosslinking or fluorescence resonance energy transfer (FRET)
      microscopy. In a study by Zhen and colleagues highlighted by this Editorial in
      the current issue of Journal of Neurochemistry, the combination of mutant and
      wild-type dopamine transporter (DAT) has been used to establish the cooperation
      between transporter protomers; the DAT mutant version has an altered affinity for
      the radiolabelled inhibitor [3H]CFT. Zhen and colleagues predict how saturation
      binding curves ought to look, if the two binding sites (i.e. of the wild type and
      the mutant DAT) operated independently. The results are clear-cut: the
      experimental observations are inconsistent with curves obtained by mixing
      independent binding sites. Thus, by definition, the binding sites cooperate. Read
      the full article 'Dopamine transporter oligomerization: impact of combining
      protomers with differential cocaine analog binding affinities' on page 167.

PMID- 25772528
TI  - The effects of counseling on fear of childbirth.
AB  - OBJECTIVE: To investigate women's experiences of attending existing counseling
      programs for childbirth-related fear and the effect of this counseling over time.
      DESIGN: A longitudinal survey. SETTING: Three hospitals in the central north of
      Sweden. SAMPLE: A selected sample of 936 women. Of these, 70 received counseling
      due to fear of childbirth (study-group). METHODS: Data were collected with
      questionnaires 2 months and 1 year after giving birth with background data
      collected during midpregnancy. Comparisons were made between women with or
      without counseling. Crude and adjusted odds ratios (OR) were calculated. MAIN
      OUTCOME MEASURES: Self-reported childbirth fear, experience of counseling, birth
      experience and preferred mode of birth. RESULTS: Women in the counseling group
      reported higher childbirth fear 1 year after giving birth (OR 5.0, 95% confidence
      interval (95% CI) 2.6-9.3), they had a more negative birth experience that did
      not change over time (OR 2.1, 95% CI 1.2-3.9) and they preferred cesarean section
      to a greater extent (OR 12.0, 95% CI 5.1-28.1) in the case of another birth.
      Also, they were more often delivered by planned cesarean section (OR 4.7, 95% CI
      2.4-9.1). However, 80% were satisfied with the given support. CONCLUSION:
      Although women were satisfied with the treatment, this study shows that
      counseling had a minor effect on fear of childbirth, birth experiences or
      cesarean section rates. To help women with their fear of childbirth, more
      effective methods of treatment are needed.

PMID- 25772526
TI  - Multimodality imaging of pericardial disease.
AB  - The emergence of multimodality imaging of pericardial diseases has improved
      diagnosis and management. In acute pericarditis, echocardiography is the first
      line test, but cardiac magnetic resonance (CMR) may be beneficial in patients who
      fail to respond to therapy. An increased T2 short-tau inversion recovery time
      (STIR) suggests pericardial edema, and increased late gadolinium enhancement
      (LGE) suggests organizing pericarditis. Computed tomography (CT) can be helpful
      in procedural planning, either to guide percutaneous drainage of an effusion or
      to assess calcification and the location of vascular structures before
      pericardiectomy. On echocardiography, a respiratory septal shift in combination
      with either a preserved medial e' velocity or prominent expiratory diastolic
      hepatic vein flow reversal performs well in diagnosing constrictive pericarditis.
      These patients also have decreased regional longitudinal strain in the
      anterolateral and right ventricular free walls, presumably related to pericardial
      to myocardial tethering. Finally, prominent LGE may identify patients with
      constrictive pericarditis who improve with anti-inflammatory therapy. 

PMID- 25772532
TI  - DNA enzymes as potential therapeutics: towards clinical application of 10-23
      DNAzymes.
AB  - INTRODUCTION: Ongoing studies on the inhibition of gene expression at the mRNA
      level have identified several types of specific inhibitors such as antisense
      oligonucleotides, small interfering RNA, ribozymes and DNAzymes (Dz). After its
      discovery in 1997, the 10-23 Dz (which can cleave RNA efficiently and site
      specifically, has flexible design, is independent from cell mechanisms, does not
      require expensive chemical modifications for effective use in vivo) has been
      employed to downregulate a range of therapeutically important genes. Recently, 10
      23 Dzs have taken their first steps into clinical trials. AREAS COVERED: This
      review focuses predominantly on Dz applications as potential antiviral,
      antibacterial, anti-cancer and anti-inflammatory agents as well as for the
      treatment of cardiovascular disease and diseases of CNS, summarizing results of
      their clinical trials up to the present day. EXPERT OPINION: In comparison with
      antisense oligonucleotides and small interfering RNAs, Dzs do not usually show
      off-target effects due to their high specificity and lack of immunogenicity in
      vivo. As more results of clinical trials carried out so far are gradually
      becoming available, Dzs may turn out to be safe and well-tolerated therapeutics
      in humans. Therefore, there is a good chance that we may witness a deoxyribozyme
      drug reaching the clinic in the near future.

PMID- 25772529
TI  - Surveillance at the molecular level: Developing an integrated network for
      detecting variation in avian influenza viruses in Indonesia.
AB  - Since 2006, Indonesia has used vaccination as the principal means of control of
      H5N1-HPAI. During this time, the virus has undergone gradual antigenic drift,
      which has necessitated changes in seed strains for vaccine production and
      associated modifications to diagnostic antigens. In order to improve the system
      of monitoring such viral evolution, the Government of Indonesia, with the
      assistance of FAO/OFFLU, has developed an innovative network whereby H5N1
      isolates are antigenically and genetically characterised. This molecular
      surveillance network ("Influenza Virus Monitoring" or "IVM") is based on the
      regional network of veterinary diagnostic laboratories, and is supported by a web
      based data management system ("IVM Online"). The example of the Indonesian IVM
      network has relevance for other countries seeking to establish laboratory
      networks for the molecular surveillance of avian influenza and other pathogens. 

PMID- 25772537
TI  - Brief Report: Autistic Features in Children and Adolescents with Gender
      Dysphoria.
AB  - This paper looks at the association between gender dysphoria (GD), scores on the
      Social Responsiveness Scale (SRS), and reported diagnoses of autism spectrum
      disorder (ASD). Parents of 166 young people presenting with GD (Mean age = 14.26,
      SD = 2.68) completed the SRS. Information concerning an ASD diagnosis was also
      extracted from the patient files. 45.8% fell within the normal range on the SRS
      and of those 2.8% had an ASD diagnosis. 27.1% fell within the mild/moderate range
      and of those 15.6% had an ASD diagnosis and 6.7% an ASD query. 27.1% fell within
      the severe range and of those 24.4% had an ASD diagnosis and 26.7% an ASD query.
      No difference was found in autistic features between the natal females and males.

PMID- 25772523
TI  - Stressful Life Events and Child Anxiety: Examining Parent and Child Mediators.
AB  - While a number of factors have been linked with excessive anxiety (e.g.,
      parenting, child temperament), the impact of stressful life events remains under
      studied. Moreover, much of this literature has examined bivariate associations
      rather than testing more complex theoretical models. The current study extends
      the literature on life events and child anxiety by testing a theory-driven
      meditational model. Specifically, one child factor (child cognitions/locus of
      control), two parent factors (parent psychopathology and parenting stress), and
      two parent-child relationship factors (parent-child dysfunctional interaction and
      parenting style) were examined as mediators in the relationship between stressful
      life events and severity of child anxiety. One hundred and thirty anxious parents
      and their nonanxious, high-risk children (ages ranged from 7 to 13 years)
      participated in this study. Results indicated that levels of parenting stress,
      parental anxious rearing, and dysfunctional parent-child interaction mediated the
      association between stressful life events and severity of anxiety symptoms. Child
      cognition and parent psychopathology factors failed to emerge as mediators.
      Findings provide support for more complex theoretical models linking life events
      and child anxiety and suggest potential targets of intervention. 

PMID- 25772536
TI  - Thriving in Youth with Autism Spectrum Disorder and Intellectual Disability.
AB  - Most research on mental health in individuals with autism spectrum disorder (ASD)
      and intellectual disability (ID) has focused on deficits. We examined individual
      (i.e., sociocommunicative skills, adaptive behavior, functional cognitive skills)
      and contextual (i.e., home, school, and community participation) correlates of
      thriving in 330 youth with ID and ASD compared to youth with ID only, 11-22 years
      of age (M = 16.74, SD = 2.95). Youth with ASD and ID were reported to thrive less
      than peers with ID only. Group differences in sociocommunicative ability and
      school participation mediated the relationship between ASD and less thriving.
      Research is needed to further elucidate a developmental-contextual framework that
      can inform interventions to promote mental health and wellness in individuals
      with ASD and ID.

PMID- 25772538
TI  - Brief Report: Preliminary Proposal of a Conceptual Model of a Digital Environment
      for Developing Mathematical Reasoning in Students with Autism Spectrum Disorders.
AB  - There is clear evidence that in typically developing children reasoning and sense
      making are essential in all mathematical learning and understanding processes. In
      children with autism spectrum disorders (ASD), however, these become much more
      significant, considering their importance to successful independent living. This
      paper presents a preliminary proposal of a digital environment, specifically
      targeted to promote the development of mathematical reasoning in students with
      ASD. Given the diversity of ASD, the prototyping of this environment requires the
      study of dynamic adaptation processes and the development of activities adjusted
      to each user's profile. We present the results obtained during the first phase of
      this ongoing research, describing a conceptual model of the proposed digital
      environment. Guidelines for future research are also discussed. 

PMID- 25772524
TI  - Change of walking distance in intermittent claudication: impact on inflammation,
      oxidative stress and mononuclear cells: a pilot study.
AB  - BACKGROUND: Atherosclerosis is a chronic inflammatory process involving the
      immune system and formation of reactive oxygen species (ROS). We investigated
      changes of mononuclear blood cells and ROS production in relation to the walking
      distance of patients with intermittent claudication during home-based exercise
      training. METHODS: Forty patients with intermittent claudication were asked to
      perform a home-based exercise training for a mean time of 12 months. ROS
      formation was measured using the luminol analogue L-012. Peripheral blood
      leucocytes [monocytes, polymorphonuclear neutrophils (PMN) and dendritic cells
      (DC)] were analysed by flow cytometry and analysed for the expression of major
      inflammatory surface molecules. RESULTS: At follow-up, patients showed an
      increased walking distance and reduced ROS production upon stimulation with a
      phorbol ester derivative (PDBu) (p < 0.01). Monocytes changed their inflammatory
      phenotype towards an increased anti-inflammatory CD14(++)CD16(-) subpopulation (p
      < 0.0001). Adhesion molecules CD11b, CD11c and TREM-1 on monocytes and PMN
      decreased (all p < 0.01). On DC expression of HLA-DR, CD86 or CD40 decreased at
      follow-up. Inflammatory markers like fibrinogen, C-reactive protein or soluble
      TREM-1 (sTREM-1) decreased over the observation period. Finally, we found a close
      relation of sTREM-1 with the walking distance, fibrinogen and ROS production.
      CONCLUSIONS: We observed an amelioration of the proinflammatory phenotype on
      monocytes, DC and PMN, as well as a reduced ROS production in PAD patients under
      home-based exercise, paralleled by an increased walking distance. Our data
      suggest that a reduced inflammatory state might be achieved by regular walking
      exercise, possibly in a dimension proportionately to changes in walking distance.

PMID- 25772539
TI  - Identification of novel peptide biomarkers to predict safety and efficacy of
      cow's milk oral immunotherapy by peptide microarray.
AB  - BACKGROUND: Cow's milk oral immunotherapy (CM-OIT) is still an experimental
      treatment. The development of novel biomarkers to predict the safety and efficacy
      of CM-OIT is crucial to translate this treatment to common clinical practice.
      OBJECTIVE: To analyse long-term changes in IgE and IgG4 epitope binding profile
      induced by CM-OIT to identify safety and efficacy biomarkers. METHODS: We studied
      25 CM-allergic children who underwent CM-OIT and seven non-treated CM-allergic
      children as controls. CM-OIT patients were classified as low, moderate, and high
      risk according to the number of allergic reactions (safety), time required to
      achieve desensitization (efficacy) and need of premedication. IgE and IgG4
      peptide microarray immunoassay was performed using a library of overlapping
      peptides of CM proteins at baseline, after oral desensitization, and 6, 12, and
      24 months of follow-up. RESULTS: Cow's milk oral immunotherapy induced a rapid
      increase of IgG4-binding epitopes and a slow decrease in IgE-binding epitopes.
      High-risk patients recognized a statistically significant higher number of IgE
      peptides in caseins at all the times studied. Similar but less pronounced changes
      were observed for IgG4-positive peptides. Clustering analysis grouped together
      the high-risk patients, and we identified 13 regions of caseins significantly
      differed between groups of patients. Bioinformatics analysis selected two sets of
      16 IgE-binding peptides at baseline that predicted safety (R(2)  = 0.858) and
      efficacy (R(2)  = 0.732), respectively, of CM-OIT. CONCLUSION AND CLINICAL
      RELEVANCE: We found two sets of IgE-binding peptides that can be used as novel
      biomarkers to predict the safety and efficacy of CM-OIT before starting
      treatment.

PMID- 25772540
TI  - Rhythm analysis and charging during chest compressions reduces compression pause
      time.
AB  - PURPOSE: Prolonged chest compression interruptions immediately preceding and
      following a defibrillation shock reduce shock success and survival after cardiac
      arrest. We tested the hypothesis that compression pauses would be shorter using
      an AED equipped with a new Analysis during Compressions with Fast Reconfirmation
      (ADC-FR) technology, which features automated rhythm analysis and charging during
      compressions with brief reconfirmation analysis during compression pause,
      compared with standard AED mode. METHODS: BLS-certified emergency medical
      technicians (EMTs) worked in pairs and performed two trials of simulated cardiac
      resuscitation with a chest compression sensing X Series defibrillator (ZOLL
      Medical). Each pair was randomized to perform a trial of eight 2-min compression
      intervals (randomly assigned to receive four shockable and four non-shockable
      rhythms) with the defibrillator in standard AED mode and another trial in ADC-FR
      mode. Subjects were advised to follow defibrillator prompts, defibrillate if
      "shock advised," and switch compressors every two intervals. Compression quality
      data were reviewed using RescueNet Code Review (ZOLL Medical) and analyzed using
      paired t-tests. RESULTS: Thirty-two EMT-basic prehospital providers (59% male;
      median 25 years age [IQR 22-27]) participated in the study. End of interval
      compression interruptions were significantly reduced with ADC-FR vs. AED mode
      (p<0.001). For shockable rhythms, pre-shock pause was reduced significantly with
      ADC-FR compared with AED use (7.35+/-0.16s vs. 12.0+/-0.22s, p<0.001) whereas
      post-shock pause was similar (2.08+/-0.14s vs. 1.77+/-0.14s, p=0.1). CONCLUSION:
      Chest compression interruptions associated with rhythm analysis and charging are
      reduced with use of a novel defibrillator technology, ADC-FR, which features
      automated rhythm analysis and charging during compressions.

PMID- 25772541
TI  - Effect of atrial fibrillation ablation on gastric motility: the atrial
      fibrillation gut study.
AB  - BACKGROUND: Collateral damage to the vagal nerve and the upper gastrointestinal
      (UGI) system during atrial fibrillation ablation has not been systematically
      evaluated. METHODS AND RESULTS: We performed a prospective, observational study
      assessing the effect of atrial fibrillation ablation on the function of the vagus
      nerve/UGI system. All patients underwent esophageal manometry, gastric emptying
      study, and sham-feeding test (corresponding to esophageal, gastric, and small
      intestinal function evaluation, respectively) before ablation (baseline) and
      subsequently at 24 hours, 90 days, and 180 days after the procedure. In addition,
      UGI symptom assessment using the patient assessment of upper gastrointestinal
      disorders-symptom severity index (PAGI-SYM) questionnaire was performed at
      baseline and during each of the subsequent evaluations. Of the 27 patients
      enrolled in the study, 9 (33%) patients had abnormal UGI function at baseline;
      defined as at least one of the 3 abnormal tests. At 24 hours after the
      radiofrequency catheter ablation, 20 (74%) patients had at least 1 new
      abnormality on the UGI function tests (P<0.001). New onset esophageal
      dysmotility, delayed gastric emptying time, and abnormal sham-feeding tests were
      observed in 13 (48%), 13 (48%), and 9 (33%) patients, respectively. Mean PAGI-SYM
      scores increased from 7.78+/-6.6 at baseline to 15.56+/-13.4 (P=0.002) at 24
      hours. New onset abnormalities persisted in 9 (33%) patients at 3 months and
      normalized in all patients at 6 months. CONCLUSIONS: Atrial fibrillation ablation
      results in functional impairment of the UGI system, including the esophagus,
      stomach, and small intestine. This impairment is transient and is probably
      mediated by the injury to the components of the vagal nerve. CLINICAL TRIAL
      REGISTRATION: URL: http://clinicaltrials.gov. Unique Identifier: NCT01396356.

PMID- 25772542
TI  - Repolarization reserve evolves dynamically during the cardiac action potential:
      effects of transient outward currents on early afterdepolarizations.
AB  - BACKGROUND: Transient outward K currents (Ito) have been reported both to
      suppress and to facilitate early afterdepolarizations (EADs) when repolarization
      reserve is reduced. Here, we used the dynamic clamp technique to analyze how Ito
      accounts for these paradoxical effects on EADs by influencing the dynamic
      evolution of repolarization reserve during the action potential. METHODS AND
      RESULTS: Isolated patch-clamped rabbit ventricular myocytes were exposed to
      either oxidative stress (H2O2) or hypokalemia to induce bradycardia-dependent
      EADs at a long pacing cycle length of 6 s, when native rabbit Ito is substantial.
      EADs disappeared when the pacing cycle length was shortened to 1 s, when Ito
      becomes negligible because of incomplete recovery from inactivation. During 6-s
      pacing cycle length, EADs were blocked by the Ito blocker 4-aminopyridine, but
      reappeared when a virtual current with appropriate Ito-like properties was
      reintroduced using the dynamic clamp (n=141 trials). During 1-s pacing cycle
      length in the absence of 4-aminopyridine, adding a virtual Ito-like current
      (n=1113 trials) caused EADs to reappear over a wide range of Ito conductance
      (0.005-0.15 nS/pF), particularly when inactivation kinetics were slow
      (tauinact>=20 ms) and the pedestal (noninactivating component) was small (<25% of
      peak Ito). Faster inactivation or larger pedestals tended to suppress EADs.
      CONCLUSIONS: Repolarization reserve evolves dynamically during the cardiac action
      potential. Whereas sufficiently large Ito can suppress EADs, a wide range of
      intermediate Ito properties can promote EADs by influencing the temporal
      evolution of other currents affecting late repolarization reserve. These findings
      raise caution in targeting Ito as an antiarrhythmic strategy.

PMID- 25772544
TI  - Daytime napping and health consequences: much epidemiologic work to do.

PMID- 25772543
TI  - Cardiac response to low-energy field pacing challenges the standard theory of
      defibrillation.
AB  - BACKGROUND: The electric response of myocardial tissue to periodic field stimuli
      has attracted significant attention as the basis for low-energy antifibrillation
      pacing, potentially more effective than traditional single high-energy shocks. In
      conventional models, an electric field produces a highly nonuniform response of
      the myocardial wall, with discrete excitations, or hot spots (HS), occurring at
      cathodal tissue surfaces or large coronary vessels. We test this prediction using
      novel 3-dimensional tomographic optical imaging. METHODS AND RESULTS: Experiments
      were performed in isolated coronary perfused pig ventricular wall preparations
      stained with near-infrared voltage-sensitive fluorescent dye DI-4-ANBDQBS. The 3
      dimensional coordinates of HS were determined using alternating
      transillumination. To relate HS formation with myocardial structures, we used
      ultradeep confocal imaging (interrogation depths, >4 mm). The peak HS
      distribution is located deep inside the heart wall, and the depth is not
      significantly affected by field polarity. We did not observe the strong
      colocalization of HS with major coronary vessels anticipated from theory. Yet, we
      observed considerable lateral displacement of HS with field polarity reversal.
      Models that de-emphasized lateral intracellular coupling and accounted for
      resistive heterogeneity in the extracellular space showed similar HS
      distributions to the experimental observations. CONCLUSIONS: The HS distributions
      within the myocardial wall and the significant lateral displacements with field
      polarity reversal are inconsistent with standard theories of defibrillation.
      Extended theories based on enhanced descriptions of cellular scale electric
      mechanisms may be necessary. The considerable lateral displacement of HS with
      field polarity reversal supports the hypothesis of biphasic stimuli in low-energy
      antifibrillation pacing being advantageous.

PMID- 25772545
TI  - A novel dithiocarbamate derivative induces cell apoptosis through p53-dependent
      intrinsic pathway and suppresses the expression of the E6 oncogene of human
      papillomavirus 18 in HeLa cells.
AB  - Dithiocarbamates (DTCs) exhibit a broad spectrum of antitumor activities,
      however, their molecular mechanisms of antitumor have not yet been elucidated.
      Previously, we have synthesized a series of novel dithiocarbamate derivatives.
      These DTCs were examined for cytotoxic activities against five human cancer cell
      lines. In this study, one of dithiocarbamate (DTC1) with higher potential for
      HeLa cells was chosen to investigate molecular mechanisms for its anti-tumor
      activities. DTC1 could inhibit proliferation, and highly induce apoptosis in HeLa
      cells by activating caspase-3, -6 and -9; moreover, activities of caspase-3, -6
      and -9 were inhibited by pan-caspase inhibitor, Z-VAD-FMK. Furthermore, DTC1
      decreased the levels of Bcl-2 and Bcl-xL, and increased expression of cytosol
      cytochrome c, Bak, Bax and p53 in a time-dependent manner but had no effect on
      the level of Rb. It was shown that DTC1 induced HeLa cells apoptosis through a
      p53-dependent pathway as tested by the wild type p53 inhibitor, pifithrin-alpha.
      Additionally, the relative expression of E6 and E7 were evaluated in HPV18
      positive (HeLa cells) by real-time PCR and western blotting. The results firstly
      demonstrated that DTC1 suppressed both expression of E6 mRNA and E6 oncoprotein,
      but had no effect on the expression of E7 mRNA and protein in HPV18. Our results
      suggested that DTC1 may serve as novel chemotherapeutic agents in the treatment
      of cervical cancer and potential anti-HPV virus candidates that merit further
      studies.

PMID- 25772546
TI  - Effect of combined radiation injury on cell death and inflammation in skin.
AB  - In the event of a nuclear disaster, the individuals proximal to the source of
      radiation will be exposed to combined radiation injury. As irradiation delays
      cutaneous repair, the purpose of this study was to elucidate the effect of
      combined radiation and burn injury (CRBI) on apoptosis and inflammation at the
      site of skin injury. Male C57Bl/6 mice were exposed to no injury, thermal injury
      only, radiation only (1 and 6 Gy) and CRBI (1 and 6 Gy) and euthanized at various
      times after for skin collection. TUNEL staining revealed that the CRBI 6 Gy group
      had a delayed and increased apoptotic response. This correlated with decreased
      recovery of live cells as compared to the other injuries. Similar response was
      observed when cleaved-caspase-3 immunohistochemical staining was compared between
      CRBI 6 Gy and thermal injury. TNFR1, caspase 8, Bax and IL-6 mRNA expression
      revealed that the higher CRBI group had delayed increase in mRNA expression as
      compared to thermal injury alone. RIPK1 mRNA expression and necrotic cell counts
      were delayed in the CRBI 6 Gy group to day 5. TNF-alpha and NFkappaB expression
      peaked in the CRBI 6 Gy group at day 1 and was much higher than the other
      injuries. Also, inflammatory cell counts in the CRBI 6 Gy group were lower at
      early time points as compared to thermal injury by itself. These data suggest
      that CRBI delays and exacerbates apoptosis and inflammation in skin as well as
      increases necrosis thus resulting in delayed wound healing. 

PMID- 25772547
TI  - [Cancer and cardiovascular disease].
AB  - Survivors of cancer have a shorter survival in the long term partly due to the
      increase in cardiovascular diseases (CVD). Some chemotherapy drugs, thoracic and
      cranial radiotherapy and above all the transplantation of hematopoietic cells are
      associated with an increase in the incidence of cardiovascular events compared
      with general population. Some of these treatments favor the development of a
      metabolic syndrome that could be the intermediary between these treatments and
      the development of CVD. It is recommended for cancer survivors to promote healthy
      lifestyles and the strict control of cardiovascular risk factors. 

PMID- 25772548
TI  - Long-term treatment with empagliflozin as add-on to oral antidiabetes therapy in
      Japanese patients with type 2 diabetes mellitus.
AB  - AIMS: To evaluate the safety and efficacy of empagliflozin for 52 weeks as add-on
      to one other oral antidiabetes therapy in Japanese patients with type 2 diabetes
      mellitus (T2DM). METHODS: Patients on biguanide (n = 133), thiazolidinedione (n =
      273), alpha-glucosidase inhibitor (n = 139), dipeptidyl-peptidase-4 inhibitor (n
      = 139) or glinide (n = 140) were randomized 1 : 1 to receive empagliflozin 10 or
      25 mg double-blind as add-on therapy for 52 weeks. Patients on sulphonylurea (SU;
      n = 336) were randomized 2 : 2 : 1 to receive empagliflozin 10 or 25 mg double
      blind or open-label metformin as add-on therapy for 52 weeks. The primary
      objective was to evaluate safety. Change from baseline in glycated haemoglobin
      (HbA1c) at week 52 was a secondary endpoint. RESULTS: Adverse events (AEs) were
      reported in 67.6-84.6% of patients receiving empagliflozin. Confirmed
      hypoglycaemic AEs (plasma glucose <=70 mg/dl and/or requiring assistance) were
      reported in 4.4 and 6.6%, respectively, of patients receiving empagliflozin 10
      and 25 mg as add-on to SU and in 0.0 to 2.9%, respectively, of patients receiving
      empagliflozin 10 and 25 mg as add-on to other therapies. Baseline mean +/-
      standard deviation HbA1c ranged from 7.51 +/- 0.73 to 8.06 +/- 0.76% across
      background therapy groups. At week 52, adjusted mean +/- standard error changes
      from baseline in HbA1c ranged from -0.77 +/- 0.06 to -1.00 +/- 0.06% in patients
      receiving empagliflozin. CONCLUSIONS: In Japanese patients with T2DM,
      empagliflozin 10 and 25 mg as add-on to one other oral antidiabetes therapy for
      52 weeks were well tolerated and were associated with clinically meaningful
      reductions in HbA1c.

PMID- 25772549
TI  - Identification and expression profiles of ERK2 and ERK5 in large yellow croaker
      (Larimichthys crocea) after temperature stress and immune challenge.
AB  - Fish is highly affected by many environmental stresses such as temperature and
      invasive infection. The extracellular signal-regulated kinase (ERK) pathway, part
      of the mitogen-activated protein kinase (MAPK) family, is found to act as crucial
      mediators for cell differentiation, proliferation and cell response to various
      stresses. In the present study, ERK2 (LcERK2) and ERK5 (LcERK2) were cloned and
      characterized from large yellow croaker, Larimichthys crocea. The full length
      cDNA sequence of LcERK2 was of 1910 bp, including an ORF of 1110bp encoding a
      polypeptide of 369 amino acids. The full length cDNA sequence of LcERK5 was of
      3720bp, including an ORF of 3375bp encoding a polypeptide of 1124 amino acids.
      Multiple alignments showed that both LcERK2 and LcERK5 contained highly conserved
      TEY motif and S_TKc domain in MAPK family and the unique catalytic and active
      structures of ERK2 and ERK5. Subcellular localization revealed that both LcERK2
      and LcERK5 expressed in the cytoplasm and cell nucleus. The expression of LcERK2
      and LcERK5 were detected in most tissues of large yellow croaker, with the most
      predominant expression of LcERK2 in brain and LcERK5 in gill, and the weakest
      expression of LcERK2 in liver and LcERK5 in intestine, respectively. The
      expression levels of LcERK2 and LcERK5 after temperature stress and poly I:C and
      flagellin challenge were investigated in LCK (L. crocea kidney) cells. After
      temperature stress, significant down-regulations of LcERK2 transcripts were
      detected after 10  degrees C stress (p < 0.05) whereas LcERK2 transcripts
      increased significantly after 35  degrees C stress (p < 0.05). However,
      significant down-regulations of LcERK5 expression were detected at most time
      points after both cold and heat stress (p < 0.05). However, significant up
      regulations of LcERK2 and LcERK5 transcripts were found after immune challenge (p
      < 0.05). Our results showed that LcERK2 transcripts enhanced after heat stress
      and both LcERK2 and LcERK5 transcripts could be induced by immune challenge.
      These findings indicated that LcERK2 might be more important in fish response to
      high temperature stress and both LcERK2 and LcERK5 might play an important role
      in fish immune response.

PMID- 25772550
TI  - A novel single WAP domain-containing protein isoform with antibacterial relevance
      in Litopenaeus vannamei.
AB  - Single WAP domain (SWD)-containing protein is a small protein containing a whey
      acidic protein (WAP) domain at the C-terminal region. SWD-containing protein
      exhibits structural similarity to the family of serine proteinase inhibitors. As
      of this writing, some SWD domain-containing proteins have been identified in
      crustaceans, and their functions included antibacterial and anti-proteinase
      activities. We identified a SWD protein isoform gene in Litopenaeus vanname (Lv
      SWDi). Very high sequence similarity was found between Lv-SWDi and Lv-SWD.
      Results of time-course analysis for the gene expression profile showed that Lv
      SWDi could produce a rapid feedback and an obvious upregulation at 12 h after
      Vibrio injection. Endogenous Lv-SWDi protein was obviously upregulated, and the
      highest expression level was reached at 24 h after Vibrio injection. The purified
      rLv-SWDi could directly bind to Gram-positive and Gram-negative bacteria. Results
      of the proteinase inhibitory assay also showed that rLv-SWDi could inhibit
      secretory protease activity from Bacillus subtilis. Lv-SWDi is a part of an
      important immunity-relevant gene and may serve important functions in defense
      against bacteria. 

PMID- 25772551
TI  - Joint blood and cerebrospinal fluid suppression for intracranial vessel wall MRI.
AB  - PURPOSE: To develop and evaluate a joint blood and cerebrospinal fluid (CSF)
      suppression technique for improved intracranial vessel wall MR imaging. METHODS:
      The Delay Alternating with Nutation for Tailored Excitation (DANTE) prepulse was
      specifically optimized for CSF suppression to improve vessel wall and CSF
      contrast. It was evaluated on six patients and three healthy volunteers. CSF
      suppression efficiency, lumen signal to noise ratio, and wall-lumen contrast to
      noise ratio were compared between images with and without DANTE in major
      intercranial artery segments. Contrast changes in tissues were also compared with
      evaluate the technique's compatibility with multicontrast imaging techniques.
      RESULTS: The optimized DANTE images significantly improved intracranial vessel
      wall characterization on all images. Quantitatively, CSF to wall contrast
      improved by 28% (DANTE-VISTA 1.354 +/- 0.216 versus VISTA 1.057 +/- 0.13; P <
      0.001). DANTE also significantly improved wall-lumen (10.55 +/- 3.79 versus 9.34
      +/- 3.54; P < 0.001) and wall-CSF (4.62 +/- 3.19 versus 0.78 +/- 2.30; P < 0.001)
      contrast-to-noise ratios. DANTE prepared images were also found to make only
      minimal impact on static tissue contrast. CONCLUSION: DANTE prepared MR imaging
      can significantly improve contrast between the vessel wall and cerebral spinal
      fluid in major intracranial arteries, holding a good potential to be combined
      with multicontrast protocol for intracranial wall imaging.

PMID- 25772552
TI  - Efficient synthesis of Au99(SR)42 nanoclusters.
AB  - We report a new synthetic protocol of Au99(SPh)42 nanoclusters with moderate
      efficiency (~15% yield based on HAuCl4), via a combination of the ligand-exchange
      and "size-focusing" processes. The purity of the as-prepared gold nanoclusters is
      characterized by matrix-assisted laser desorption ionization mass spectrometry
      and size exclusion chromatography. 

PMID- 25772553
TI  - Psychological functioning of people living with chronic pain: a meta-analytic
      review.
AB  - OBJECTIVES: Chronic pain (CP; >3 months) is a common condition that is associated
      with significant psychological problems. Many people with CP do not fit into
      discrete diagnostic categories, limiting the applicability of research that is
      specific to a particular pain diagnosis. This meta-analysis synthesized the large
      extant literature from a general CP, rather than diagnosis-specific, perspective
      to systematically identify and compare the psychological problems most commonly
      associated with CP. METHODS: Four databases were searched from inception to
      December 2013 (PsychINFO, The Cochrane Library, Scopus, and PubMed) for studies
      comparing the psychological functioning of adults with CP to healthy controls.
      Data from 110 studies were meta-analysed and Cohen's d effect sizes calculated.
      RESULTS: The CP group reported experiencing significant problems in a range of
      psychological domains (depression, anxiety, somatization, anger/hostility, self
      efficacy, self-esteem and general emotional functioning), with the largest
      effects observed for pain anxiety/concern and somatization; followed by anxiety
      and self-efficacy; and then depression, anger/hostility, self-esteem and general
      emotional functioning. CONCLUSIONS: This study demonstrates, for the first time,
      that individuals with CP are more likely to experience physically focussed
      psychological problems than other psychological problems and that, unlike self
      efficacy, fear of pain is intrinsically tied to the CP experience. This
      challenges the prevailing view that, for individuals with CP, problems with
      depression are either equal to, or greater than, problems with anxiety, thereby
      providing important information to guide therapeutic targets. PRACTITIONER
      POINTS: Positive clinical implications: This is the first time that the CP
      literature has been synthesized from a general perspective to examine
      psychological functioning in the presence of CP and provide practical
      recommendations for assessment and therapy. Individuals with CP were most likely
      to experience psychological problems in physically focussed areas - namely pain
      anxiety/concern and somatization. Although fear of pain was intrinsically tied to
      the CP experience, self-efficacy was not. CP was more strongly associated with
      anxiety than with depression. Limitations The study focuses on the general CP
      literature, adults and research-utilizing self-report measures. Meta-analyses are
      limited by the empirical literature on which they are based.

PMID- 25772554
TI  - Action video games and improved attentional control: Disentangling selection- and
      response-based processes.
AB  - Research has demonstrated that experience with action video games is associated
      with improvements in a host of cognitive tasks. Evidence from paradigms that
      assess aspects of attention has suggested that action video game players (AVGPs)
      possess greater control over the allocation of attentional resources than do non
      video-game players (NVGPs). Using a compound search task that teased apart
      selection- and response-based processes (Duncan, 1985), we required participants
      to perform an oculomotor capture task in which they made saccades to a uniquely
      colored target (selection-based process) and then produced a manual directional
      response based on information within the target (response-based process). We
      replicated the finding that AVGPs are less susceptible to attentional distraction
      and, critically, revealed that AVGPs outperform NVGPs on both selection-based and
      response-based processes. These results not only are consistent with the improved
      attentional-control account of AVGP benefits, but they suggest that the benefit
      of action video game playing extends across the full breadth of attention
      mediated stimulus-response processes that impact human performance.

PMID- 25772555
TI  - Behavior of PAH/mineral associations during thermodesorption: impact for the
      determination of mineral retention properties towards PAHs.
AB  - Polycyclic aromatic hydrocarbons (PAHs) associated with two minerals (silica sand
      and bentonite) presenting opposite retention properties were analyzed with a
      thermodesorption (Td)-GC-MS coupling in order to validate this technique as a new
      and rapid way to evaluate the solid sorption properties. Two analysis modes were
      used, evolved gas analysis (EGA) and Td with cryo-trap. EGA allowed a real-time
      monitoring of the compounds desorbed during a temperature program and gave a
      first screening of the samples while Td gave more precise indications on compound
      abundances for selected temperature ranges. When associated with silica sand,
      PAHs were released at relatively low temperatures (<300  degrees C) close to
      corresponding boiling point, whereas for the PAH/bentonite mixture, PAHs were
      desorbed at much higher temperatures; they were also present in much lower
      abundance and were associated with mono-aromatic compounds. With bentonite, the
      PAH abundances decreased and the mono-aromatics increased with the increasing PAH
      molecular weight. These results indicated a clear PAH retention by the bentonite
      due to polymerization, followed by a thermal cracking at higher temperatures. The
      Td-GC-MS was proven to efficiently underline differences in retention properties
      of two minerals, and this study highlights the great potential of this technique
      to evaluate compound/matrix bond strength and interaction. 

PMID- 25772556
TI  - A review of electrochemiluminescence (ECL) in and for microfluidic analytical
      devices.
AB  - The concept and realization of microfluidic total analysis systems (microTAS)
      have revolutionized the analytical process by integrating the whole breadth of
      analytical techniques into miniaturized systems. Paramount for efficient and
      competitive microTAS are integrated detection strategies, which lead to low
      limits of detection while reducing the sample volume. The concept of
      electrochemiluminescence (ECL) has been intriguing ever since its introduction
      based on Ru(bpy)3 (2+) by Tokel and Bard [1] (J Am Chem Soc 1853:2862-2863,
      1972), especially because of its immense sensitivity, nonexistent auto
      luminescent background signal, and simplicity in experimental design. Therefore,
      integrating ECL detection into microTAS is a logical consequence to achieve
      simple, yet highly sensitive, sensors. However, published microanalytical devices
      employing ECL detection focus in general on traditional ECL chemistry and have
      yet to take advantage of advances made in standard bench-top ECL strategies. This
      review will therefore focus on the most recent advancements in microfluidic ECL
      approaches, but also evaluate the potential impact of bench-top ECL research
      progress that would further improve performance and lower limits of detection of
      micro analytical ECL systems, ensuring their desirability as detection principle
      for microTAS applications. 

PMID- 25772557
TI  - A multi-analyte biosensor for the simultaneous label-free detection of pathogens
      and biomarkers in point-of-need animal testing.
AB  - For the first time, a multi-analyte biosensor platform has been developed using
      the label-free 1-lambda-reflectometry technique. This platform is the first,
      which does not use imaging techniques, but is able to perform multi-analyte
      measurements. It is designed to be portable and cost-effective and therefore
      allows for point-of-need testing or on-site field-testing with possible
      applications in diagnostics. This work highlights the application possibilities
      of this platform in the field of animal testing, but is also relevant and
      transferable to human diagnostics. The performance of the platform has been
      evaluated using relevant reference systems like biomarker (C-reactive protein)
      and serology (anti-Salmonella antibodies) as well as a panel of real samples
      (animal sera). The comparison of the working range and limit of detection shows
      no loss of performance transferring the separate assays to the multi-analyte
      setup. Moreover, the new multi-analyte platform allows for discrimination between
      sera of animals infected with different Salmonella subtypes. 

PMID- 25772559
TI  - Direct optical detection.

PMID- 25772558
TI  - In vitro and in vivo metabolism of ochratoxin A: a comparative study using ultra
      performance liquid chromatography-quadrupole/time-of-flight hybrid mass
      spectrometry.
AB  - Ochratoxin A (OTA) is a mycotoxin that frequently contaminates a wide variety of
      food and feedstuffs. The metabolism of OTA greatly affects fate and toxicity in
      humans and animals, because of its possible carcinogenic character (International
      Agency for Research on Cancer (IARC), group 2B). To completely characterize the
      metabolites of OTA, the metabolism of OTA in liver microsomes of rats, chickens,
      swine, goats, cows, and humans was investigated using ultra-performance liquid
      chromatography-quadrupole/time-of-flight hybrid mass spectrometry (UPLC-Q/TOF
      MS). In addition, an in vivo comparative metabolism study of OTA was performed
      among rats and chickens after oral administration of OTA. As a result, a clear
      metabolic profile of OTA in different species was proposed, and a total of eight
      metabolites were identified, of which three hydroxylated metabolites at the
      phenylalanine moiety were discovered for the first time (preliminarily identified
      as 9'-OH-OTA, 7'-OH-OTA, and 5'-OH-OTA). Considerable amounts of 7'-OH-OTA were
      detected in different species' liver microsomes, especially in chickens and
      humans. Moreover, the metabolism of OTA in chickens was elucidated for the first
      time in the present study. The 7'-OH-OTA proved to be the main metabolite in
      vitro and in vivo in chickens. Furthermore, the 4(S)-OH-OTA isomer was the major
      one, and 4(R)-OH-OTA the minor metabolite in chickens, which was different from
      others where 4R was the major. OTA undergoes metabolism via three different
      pathways, namely hydroxylation, dechlorination, and conjugation. The proposed
      metabolic pathways of OTA in various species provide the scientific community
      useful data for the toxicological safety evaluation of OTA among different
      species, and will further facilitate the food safety evaluation of OTA. 

PMID- 25772560
TI  - Determination of illicit drugs and metabolites in oral fluid by microextraction
      on packed sorbent coupled with LC-MS/MS.
AB  - Oral fluid (OF) has become a valuable biologic specimen for toxicological
      analysis, especially in driving under the influence of drugs (DUID)
      investigations, because of easy and non-invasive collection procedures. In OF
      testing, being the sample volume is limited, multi-analyte procedures are
      particularly advantageous since they save time and resources. In this work, a
      procedure for the simultaneous analysis of 20 illicit drugs, belonging to the
      classes of cocaine, amphetamines, natural and synthetic opioids and
      hallucinogens, is presented. The sample preparation is based on microextraction
      by packed sorbent (MEPS), a novel technique which is based on the miniaturization
      of solid-phase extraction (SPE). The presented method, which includes all the
      most diffused illicit drugs and their metabolites, has been fully validated
      according to the Scientific Working Group for Forensic Toxicology (SWGTOX)
      guidelines. LLOQs ranged from 0.5 to 30 ng mL(-1) (diacetylmorphine); the
      presented method allows the detection of all the selected drugs quite below the
      cutoff values recommended by Substance Abuse and Mental Health Services
      Administration (SAMHSA) for abuse identification. 

PMID- 25772561
TI  - Exploring matrix effects in liquid chromatography-tandem mass spectrometry
      determination of pesticide residues in tropical fruits.
AB  - Tropical fruits are being increasingly consumed around the world because of their
      appreciated characteristics, particularly their high nutritional value and
      distinctive taste, which are different from those of traditional fruits. Owing to
      their introduction into international markets it is necessary to have a reliable
      analytical methodology available for the sensitive determination of pesticide
      residues in order to monitor the compliance of maximum residue limits (MRLs).
      From an analytical point of view, tropical fruits have generally been far less
      studied than other fruits frequently consumed in the European Union or USA, which
      are among the most important markets. In this work, LC-MS/MS-based methodology
      using a triple quadrupole analyzer was developed for the multi-residue
      determination of selected pesticides and metabolites in tropical fruits, which
      were selected among the most popular in Colombia, one of the most important
      suppliers of tropical fruits around the world. After selection of a QuEChERS
      (Quick, Easy, Cheap, Effective, Rugged, and Safe)-based sample treatment, the
      study focused on the evaluation of matrix effects, in order to find a simple way
      for their correction. Twelve different food matrices were selected to perform
      this study: the seven Colombian tropical fruits of highest value for domestic and
      international markets (uchuva, tamarillo, granadilla, gulupa, maracuya, papaya,
      and pithaya), and five more matrices highly consumed in Colombia (lulo,
      carambolo, feijoa, mangostan, and guayaba). Twenty compounds, including
      pesticides widely applied in tropical fruits pest control and several metabolites
      considered in residue definition, were used as model compounds in this work.
      Correction factors were used on the basis of calibration graphs obtained with
      standards in solvent and in matrix, and their usefulness was supported by
      validation of the method in all the matrices tested at 0.01 and 0.1 mg/kg. The
      analysis of real-world samples revealed the presence of several target compounds
      that were identified by the acquisition of two MS/MS transitions, and by ion
      intensity ratio and retention time agreement. 

PMID- 25772562
TI  - Cysteine residue is not essential for CPM protein thermal-stability assay.
AB  - A popular thermal-stability assay developed especially for the study of membrane
      proteins uses a thiol-specific probe, 7-diethylamino-3-(4-maleimidophenyl)-4
      methylcoumarin (CPM). The fluorescence emission of CPM surges when it forms a
      covalent bond with the side chain of a free Cys, which becomes more readily
      accessible upon protein thermal denaturation. Interestingly, the melting
      temperatures of membrane proteins determined using the CPM assay in literature
      are closely clustered in the temperature range 45-55  degrees C. A thorough
      understanding of the mechanism behind the observed signal change is critical for
      the accurate interpretation of the protein unfolding. Here we used two alpha
      helical membrane proteins, AqpZ and AcrB, as model systems to investigate the
      nature of the fluorescence surge in the CPM assay. We found that the transition
      temperatures measured using circular-dichroism (CD) spectroscopy and the CPM
      assay were significantly different. To eliminate potential artifact that might
      arise from the presence of detergent, we monitored the unfolding of two soluble
      proteins. We found that, contrary to current understanding, the presence of a
      sulfhydryl group was not a prerequisite for the CPM thermal-stability assay. The
      observed fluorescence increase is probably caused by binding of the fluorophore
      to hydrophobic patches exposed upon protein unfolding. 

PMID- 25772563
TI  - Rapid ultra-trace analysis of sucralose in multiple-origin aqueous samples by
      online solid-phase extraction coupled to high-resolution mass spectrometry.
AB  - Because of its widespread consumption and its persistence during wastewater
      treatment, the artificial sweetener sucralose has gained considerable interest as
      a proxy to detect wastewater intrusion into usable water resources. The molecular
      resilience of this compound dictates that coastal and oceanic waters are the
      final recipient of this compound with unknown effects on ecosystems. Furthermore,
      no suitable methodologies have been reported for routine, ultra-trace detection
      of sucralose in seawater as the sensitivity of traditional liquid chromatography
      tandem mass spectrometry (LC-MS/MS) analysis is limited by a low yield of product
      ions upon collision-induced dissociation (CID). In this work, we report the
      development and field test of an alternative analysis tool for sucralose in
      environmental waters, with enough sensitivity for the proper quantitation and
      confirmation of this analyte in seawater. The methodology is based on automated
      online solid-phase extraction (SPE) and high-resolving-power orbitrap MS
      detection. Operating in full scan (no CID), detection of the unique isotopic
      pattern (100:96:31 for [M-H](-), [M-H+2](-), and [M-H+4](-), respectively) was
      used for ultra-trace quantitation and analyte identification. The method offers
      fast analysis (14 min per run) and low sample consumption (10 mL per sample) with
      method detection and confirmation limits (MDLs and MCLs) of 1.4 and 5.7 ng/L in
      seawater, respectively. The methodology involves low operating costs due to
      virtually no sample preparation steps or consumables. As an application example,
      samples were collected from 17 oceanic and estuarine sites in Broward County, FL,
      with varying salinity (6-40 PSU). Samples included the ocean outfall of the
      Southern Regional Wastewater Treatment Plant (WWTP) that serves Hollywood, FL.
      Sucralose was detected above MCL in 78% of the samples at concentrations ranging
      from 8 to 148 ng/L, with the exception of the WWTP ocean outfall (at pipe end, 28
      m below the surface) where the measured concentration was 8418 +/- 3813 ng/L.
      These results demonstrate the applicability of this monitoring tool for the trace
      level detection of this wastewater marker in very dilute environmental waters.

PMID- 25772564
TI  - Alternative QuEChERS-based modular approach for pesticide residue analysis in
      food of animal origin.
AB  - The approach for pesticide residue analysis in food of animal origin differs
      strongly from the one established for food of plant origin, as laboratories
      mainly focus on conventional methods for the analysis of non-polar pesticides
      known to accumulate in fatty tissues. However, these group-specific methods are
      very laborious and cost intensive and typically require extraction of fat
      components followed by extensive clean-up steps to remove matrix constituents.
      This work highlights the development and validation of a straightforward QuEChERS
      derived clean-up procedure enabling facile, precise, and reliable identification
      and quantitation of pesticide residues in food of animal origin, which can be
      extended to various other commodities with moderate fat content and applied to
      replace traditional group-specific methods. Two additional methods for lean and
      highly fatty commodities complete this well-established "simplified modular
      system". The proposed method was in-house validated in terms of accuracy and
      precision, recovery and linearity as well as specificity and sensitivity on two
      representative commodities for food of animal origin (egg and meat). For the
      majority of the more than 80 pesticides investigated, satisfactory results were
      obtained. Procedural matrix calibration was applied for screening purposes in
      conjunction with GC-MS/MS or LC-MS/MS as integral part of the approach. Apparent
      recoveries for most of the compounds ranged from 70 to 120 % (RSD < 20%) at
      spiking levels of 0.01 (LOQ level) and 0.05 mg/kg. Accuracy of the method has
      been demonstrated by application to reference material from previous EU
      proficiency tests. Only in case of positive screening results a standard addition
      approach was applied for precise quantitation.

PMID- 25772565
TI  - Differential proteomic analysis of mouse macrophages exposed to adsorbate-loaded
      heavy fuel oil derived combustion particles using an automated sample-preparation
      workflow.
AB  - Ship diesel combustion particles are known to cause broad cytotoxic effects and
      thereby strongly impact human health. Particles from heavy fuel oil (HFO)
      operated ships are considered as particularly dangerous. However, little is known
      about the relevant components of the ship emission particles. In particular, it
      is interesting to know if the particle cores, consisting of soot and metal
      oxides, or the adsorbate layers, consisting of semi- and low-volatile organic
      compounds and salts, are more relevant. We therefore sought to relate the
      adsorbates and the core composition of HFO combustion particles to the early
      cellular responses, allowing for the development of measures that counteract
      their detrimental effects. Hence, the semi-volatile coating of HFO-operated ship
      diesel engine particles was removed by stepwise thermal stripping using different
      temperatures. RAW 264.7 macrophages were exposed to native and thermally stripped
      particles in submersed culture. Proteomic changes were monitored by two different
      quantitative mass spectrometry approaches, stable isotope labeling by amino acids
      in cell culture (SILAC) and dimethyl labeling. Our data revealed that cells
      reacted differently to native or stripped HFO combustion particles. Cells exposed
      to thermally stripped particles showed a very differential reaction with respect
      to the composition of the individual chemical load of the particle. The cellular
      reactions of the HFO particles included reaction to oxidative stress,
      reorganization of the cytoskeleton and changes in endocytosis. Cells exposed to
      the 280  degrees C treated particles showed an induction of RNA-related
      processes, a number of mitochondria-associated processes as well as DNA damage
      response, while the exposure to 580  degrees C treated HFO particles mainly
      induced the regulation of intracellular transport. In summary, our analysis based
      on a highly reproducible automated proteomic sample-preparation procedure shows a
      diverse cellular response, depending on the soot particle composition. In
      particular, it was shown that both the molecules of the adsorbate layer as well
      as particle cores induced strong but different effects in the exposed cells. 

PMID- 25772566
TI  - Examining concentrations and molecular weights of thiols in microorganism
      cultures and in Churchill River (Manitoba) using a fluorescent-labeling method
      coupled to asymmetrical flow field-flow fractionation.
AB  - In this study, molecular weights of thiols from four laboratory cultures
      (Scenedesmus obliquus, Chlorella vulgaris, Euglena gracilis, and Attheya
      septentrionalis) and the Churchill River (Manitoba) were assessed using a
      fluorescent-labeling method such as monobromotrimethylammoniobimane (qBBr) and
      asymmetrical flow field-flow fractionation (AF4) coupled to a fluorescence
      detector. Concentrations of thiols in extracellular fractions ranged from 6.39 +/
      3.39 to 39.2 +/- 7.43 MUmol g(-1), and intracellular concentrations ranged from
      11.5 +/- 4.52 to 41.0 +/- 4.1 MUmol g(-1). In addition, molecular weights (MW) of
      intracellular thiol ranged from 493 +/- 24 to 946 +/- 12 Da whereas extracellular
      thiol MWs varied from 443 +/- 36 to 810 +/- 174 Da. The novel method of combining
      AF4 to an on-line fluorometer and the incorporation of the thiol tag provided
      information regarding thiol concentration and composition of controlled and
      natural systems. Furthermore, the proposed methods allow for the simultaneous
      measurement of thiol and DOM MWs produced by microorganisms. By assessing
      characteristics of naturally produced thiols and lab-grown thiols, information
      regarding heavy metal complexation can be determined. 

PMID- 25772567
TI  - Simultaneous LC-MS/MS determination of JWH-210, RCS-4, ?(9)-tetrahydrocannabinol,
      and their main metabolites in pig and human serum, whole blood, and urine for
      comparing pharmacokinetic data.
AB  - A series of new synthetic cannabinoids (SC) has been consumed without any
      toxicological testing. For example, pharmacokinetic data have to be collected
      from forensic toxicological case work and/or animal studies. To develop a
      corresponding model for assessing such data, samples of controlled pig studies
      with two selected SC (JWH-210, RCS-4) and, as reference, ?(9)
      tetrahydrocannabinol (THC) should be analyzed as well as those of human cases.
      Therefore, a method for determination of JWH-210, RCS-4, THC, and their main
      metabolites in pig and human serum, whole blood, and urine samples is presented.
      Specimens were analyzed by liquid-chromatography tandem mass spectrometry and
      multiple-reaction monitoring with three transitions per compound. Full validation
      was carried out for the pig specimens and cross-validation for the human
      specimens concerning precision and bias. For the pig studies, the limits of
      detection were between 0.05 and 0.50 ng/mL in serum and whole blood and between
      0.05 and 1.0 ng/mL in urine, the lower limits of quantification between 0.25 and
      1.0 ng/mL in serum and 0.50 and 2.0 ng/mL in whole blood and urine, and the intra
      and interday precision values lower than 15% and bias values within +/-15%. The
      applicability was tested with samples taken from a pharmacokinetic pilot study
      with pigs following intravenous administration of a mixture of 200 MUg/kg body
      mass dose each of JWH-210, RCS-4, and THC. The cross-validation data for human
      serum, whole blood, and urine showed that this approach should also be suitable
      for human specimens, e.g., of clinical or forensic cases.

PMID- 25772568
TI  - Cr(VI) speciation in foods by HPLC-ICP-MS: investigation of Cr(VI)/food
      interactions by size exclusion and Cr(VI) determination and stability by ion
      exchange on-line separations.
AB  - A method has been developed for the specific and sensitive determination of
      Cr(VI) in foods. First, the interactions between Cr(VI) and the matrices were
      investigated by size-exclusion HPLC-ICP-MS (SEC-ICP-MS). Evidence was found for
      the complexation of Cr(VI) potentially present with the ligands. For
      quantification of Cr(VI), the method was based on an alkaline extraction (NH4OH
      solution at pH 11.5) followed by Cr(VI) determination by anion-exchange HPLC-ICP
      MS. Analytical performances of the method were satisfactory in terms of
      linearity, specificity, accuracy, repeatability, and intermediate precision.
      Detection limits ranged from 1 to 10 MUg/kg, depending on the matrices
      investigated. The method was then applied for the determination of Cr(VI) in
      several products (dairy products, flour, chocolate, vegetables, fruits, meat,
      fish, eggs, and beverages) from different brands and origins. Cr(VI) was found in
      none of the samples investigated. To further investigate the reason for this
      absence, a stability study of spiked Cr(VI) was therefore conducted. A semi
      skimmed cow milk was selected for this study. Cr(VI) was shown to be unstable in
      this matrix with a degradation rate increasing with the temperature. 

PMID- 25772569
TI  - Sequential Percutaneous LAA Ligation and Pulmonary Vein Isolation in Patients
      with Persistent AF: Initial Results of a Feasibility Study.
AB  - INTRODUCTION: Left atrial appendage (LAA) ligation results in LAA electrical
      isolation and a decrease in atrial fibrillation (AF) burden. This study assessed
      the feasibility of combined percutaneous LAA ligation and pulmonary vein
      isolation (PVI) in patients with persistent AF. METHODS AND RESULTS: A total of
      22 patients with persistent AF underwent LAA ligation with the LARIAT device
      followed by PVI. PVI was confirmed with the demonstration of both entrance and
      exit block. Patients (n = 10) in sinus rhythm pre- and post-LAA ligation
      underwent P-wave analysis. Monitoring for AF was performed at 1, 3, and 6 months
      postablation. LAA ligation was successful in 21 of 22 (95%) patients. The
      procedure was aborted in one patient due to pericardial adhesions. PVI was
      performed in 20 of 21 patients. One patient converted to atrial flutter with a
      controlled ventricular response after LAA ligation and refused subsequent PVI.
      Demonstration of entrance and exit block was achieved in 19 of 20 patients. At 3
      months, 13 of 19 (68.4%) patients were in sinus rhythm. Four patients underwent a
      second PVI. At 6 months, 15 of 20 (75%) patients were in sinus rhythm. There was
      a significant decrease in P-wave duration and P-wave dispersion after LAA
      ligation. Complications with LAA ligation included pericarditis, a delayed
      pleural effusion, and a late pericardial effusion. CONCLUSIONS: Staged LAA
      ligation and PVI is feasible and decreases P-wave dispersion. Randomized studies
      are needed to assess the efficacy of LAA ligation as adjunctive therapy to PVI
      for maintaining sinus rhythm in patients with persistent AF.

PMID- 25772570
TI  - Promotion of expression of interferon-stimulated genes in U937 monocytic cells by
      HIV RNAs, measured using stable isotope labeling with amino acids in cell culture
      (SILAC).
AB  - Type I interferon (IFN) exerts strong antiviral activity, particularly against
      human immunodeficiency virus (HIV), and although several viral proteins have been
      shown to deregulate IFN induction, little is known about the induction of type I
      IFNs by HIV RNAs. In the present study, we used the stable isotope labeling with
      amino acids in cell culture (SILAC) method to determine the proteomic profile in
      U937 monocytic cells after transfection with viral RNA of HIV. We then used a
      western blot assay to validate the proteomic results. It was revealed by the
      SILAC method that there were 1624 non-redundant peptides with quantitative
      information and 281 proteins with quantitative information in the HIV-RNA
      transfected U937 cells when compared to cells transfected with control RNA. In
      particular, 6, 8 or 12 hours post-transfection, HIV RNA transfection promoted the
      expression of such interferon stimulated genes (ISGs) as interferon-induced
      proteins with tetratricopeptide repeats (IFITs), interferon-induced transmembrane
      proteins (IFITMs), interferon-induced gene 15 protein (ISG15), myxovirus
      (influenza virus) resistance protein 1 (MX1), and interferon-induced guanylate
      binding protein 1 (GBP1), and this was confirmed by western blot assay. In
      conclusion, HIV RNA is a strong stimulator of IFNs, promoting the expression of
      such ISGs as IFITs, IFITMs, ISG15, MX1 and GBP1.

PMID- 25772571
TI  - Complete genome sequences of two new virus isolates associated with cotton blue
      disease resistance breaking in Brazil.
AB  - Since 2006, Brazilian cotton (Gossypium hirsutum) crops planted with cultivars
      that are resistant to cotton blue disease have developed a new disease termed
      "atypical" cotton blue disease or atypical vein mosaic disease. Here, we describe
      the complete genomes of two virus isolates associated with this disease. The new
      virus isolates, called CLRDV-Acr3 and CLRDV-IMA2, were found to have a high
      degree of nucleotide and amino acid sequence similarity to previously described
      isolates of cotton leafroll dwarf virus, the causal agent of cotton blue disease.
      However, their P0 proteins were 86.1 % identical. These results show that this
      new disease is caused by a new CLRDV genotype that seems to have acquired the
      ability to overcome cotton blue disease resistance. 

PMID- 25772572
TI  - Cotton leaf curl Burewala virus with intact or mutant transcriptional activator
      proteins: complexity of cotton leaf curl disease.
AB  - Cotton leaf curl disease (CLCuD) is a serious disease of cotton on the Indian
      subcontinent. In the present study, three cotton leaf curl viruses, cotton leaf
      curl Burewala virus (CLCuBuV), cotton leaf curl Kokhran virus (CLCuKoV) and
      cotton leaf curl Multan virus (CLCuMV), and their associated satellites, cotton
      leaf curl Multan betasatellite (CLCuMB) and cotton leaf curl Multan
      alphasatellite (CLCuMA), were detected. CLCuBuV with either intact (CLCuBuV-1) or
      mutant (CLCuBuV-2) transcriptional activator protein (TrAP) were detected in
      different plants. Agroinoculation with CLCuBuV-1 or CLCuBuV-2 together with
      CLCuMB and CLCuMA, resulted in typical leaf curling and stunting of tobacco
      plants. Inoculation with CLCuKoV or an isolate of CLCuMV (CLCuMV-2), together
      with CLCuMB and CLCuMA, induced severe leaf curling, while the other isolate of
      CLCuMV (CLCuMV-1), which was recombinant in origin, showed mild leaf curling in
      tobacco. To investigate the effect of intact or mutant TrAP and also the
      recombination events, CLCuBuV-1, CLCuBuV-2, CLCuMV-1 or CLCuMV-2 together with
      the satellites (CLCuMA and CLCuMB) were transferred to cotton via whitefly
      mediated transmission. Cotton plants containing CLCuBuV-1, CLCuBuV-2 or CLCuMV-2
      together with satellites showed curling and stunting, whereas the plants having
      CLCuMV-1 and the satellites showed only mild and indistinguishable symptoms.
      CLCuBuV-1 (intact TrAP) showed severe symptoms in comparison to CLCuBuV-2 (mutant
      TrAP). The present study reveals that two types of CLCuBuV, one with an intact
      TrAP and the other with a mutant TrAP, exist in natural infection of cotton in
      India. Additionally, CLCuMuV-1, which has a recombinant origin, induces mild
      symptoms in comparison to the other CLCuMV isolates.

PMID- 25772573
TI  - Comparative evaluation of nucleic acid-based assays for detection of Japanese
      encephalitis virus in swine blood samples.
AB  - Japanese encephalitis is an emerging mosquito-borne flaviviral zoonotic disease.
      The present study was undertaken with the objective of developing rapid and
      sensitive nucleic-acid-based assays for detection of Japanese encephalitis virus
      (JEV) in swine blood samples. Three nucleic-acid-based assays, viz., reverse
      transcription polymerase chain reaction (RT-PCR), reverse transcription loop
      mediated isothermal amplification (RT-LAMP), and real-time RT-PCR, were developed
      and compared in terms of their diagnostic efficacy. All three assays were found
      to be 100 per cent specific. The minimum detection limit of RT-LAMP and real-time
      RT-PCR was 12 copies/ul, while RT-PCR could detect 1.2 * 10(5) copies/ul. On
      comparison, RT-LAMP and real-time RT-PCR were 4-log more sensitive than RT-PCR.
      The applicability of the assays was evaluated by screening 135 field swine blood
      samples, of which 24 (17.77 %) were positive by RT-LAMP and real-time RT-PCR and
      only six (4.44 %) were positive by RT-PCR. The viral load in swine blood samples
      ranged between 2 * 10(6) and 4.8 * 10(9) copies per ml of blood by real-time RT
      PCR. The comparative diagnostic sensitivity and specificity of RT-LAMP vis-a-vis
      real-time RT-PCR was found to be 100 %, while the sensitivity and specificity of
      RT-PCR vis-a-vis real-time RT-PCR was found to be 25 % and 100 %, respectively.
      Thus, the use of RT-PCR may cause the incidence of JEV in the swine population to
      be underestimated, while the real-time RT-PCR reported here is the test of choice
      for reference laboratories, and the newly developed one-step RT-LAMP assay will
      be suitable for field-level testing.

PMID- 25772574
TI  - Molecular characterization and multiple infections of rotavirus, norovirus,
      sapovirus, astrovirus and adenovirus in outpatients with sporadic gastroenteritis
      in Shanghai, China, 2010-2011.
AB  - Rotavirus (RV), norovirus (NoV), sapovirus (SaV), human astrovirus (HAstV) and
      human adenovirus (HAdV) are significant because they are the most common
      pathogens that cause diarrhea in young children. The aim of this study was to
      investigate the genetic characteristics and compare the roles of these five
      viruses in outpatient children with diarrhea in Shanghai. A total of 436 fecal
      samples were collected from pediatric patients with acute gastroenteritis from
      January 2010 to December 2011. The selected samples were subjected to reverse
      transcription PCR (RT-PCR) or PCR to detect and genotype RV, NoV, SaV, HAstV and
      HAdV. RV (43.3 %, 189/436) was the most prevalent virus, followed by NoV (28.9 %,
      126/436), HAdV (7.1 %, 31/436). HAstV (1.8 %, 8/436) and SaV (0.5 %, 2/436). The
      percentage of multiple infection cases was 14.9 % (65/436), and RV + NoV was the
      predominant mixed infection. The RV genotype combinations of P[8]G3 (52/189, 27.5
      %), P[8]G1 (51/189, 26.9 %) and P[8]G9 (48/189, 25.4 %) occurred most frequently.
      The predominant NoV genotype was GII.4 (73.0 %, 92/126), and the majority of
      GII.4 clustered as GII.4-2006b (65.2 %, 60/92). Two of the SaV cases were
      identified as GI.2 and GII.1. All HAstV-positive samples belonged to HAstV-1. The
      predominant HAdV type was HAdV-41 (45.2 %, 14/31). This study clearly shows the
      diversity of the viral causative agents of acute gastroenteritis in outpatient
      children in Shanghai, which will provide baseline information for future
      vaccination strategies and development in this area.

PMID- 25772575
TI  - Molecular characterization of group A rotavirus strains detected in children with
      diarrhea admitted to Nigerian hospitals in 2013.
AB  - Group A rotaviruses (RVA) are the leading cause of acute gastroenteritis (AGE) in
      children worldwide and cause up to 455,000 deaths annually, mostly in developing
      countries. During 2013, 66 RVAs from children with AGE admitted to four Nigerian
      hospitals were investigated. The G3P[6], G1P[8] and G2P[4] genotypes
      predominated. The VP7 and/or VP4 genes of 18 G3P[6]/[8]/[4], six G2P[4], three
      G12P[8]/[4], and two G1P[8] RVA strains were sequenced. The G3P[6] strains
      belonged to lineage G3-III and were different from G3 strains widespread in Asia.
      Phylogenetic analysis revealed substantial sequence conservation, suggesting
      continuing evolution and genomic reassortment but no zoonotic RVA transmission
      from animals.

PMID- 25772576
TI  - Molecular and serological evidence for Seoul virus in rats (Rattus norvegicus) in
      Zhangmu, Tibet, China.
AB  - We report the detection of a virus, tentatively identified as Seoul virus (SEOV),
      from a rat (Rattus norvegicus) collected in the city of Zhangmu, Tibet. SEOV RNA
      was detected in lung tissue by reverse transcription (RT)-PCR, followed by
      sequencing. Serum samples collected from Zhangmu were positive for SEOV-specific
      antibodies (indirect fluorescent antibody test that used SEO antigen). Sequencing
      and phylogenetic analysis of partial L and S sequences together with serology
      results suggest that the Zhangmu01 hantavirus is an isolate of SEOV, that
      hantaviruses circulate in Tibet, and that rats may act as natural reservoirs for
      the virus. 

PMID- 25772577
TI  - DRACO inhibits porcine reproductive and respiratory syndrome virus replication in
      vitro.
AB  - Porcine reproductive and respiratory syndrome virus (PRRSV) continues to cause
      substantial economic losses to the pig industry worldwide. Current vaccination
      strategies and antiviral drugs against PRRSV are still inadequate. Therefore,
      there is an urgent need for new antiviral strategies to control PRRSV. Double
      stranded RNA (dsRNA) Activated Caspase Oligomerizer (DRACO) is a synthetic
      construct consisting of a dsRNA detection domain, an apoptosis induction domain,
      and a transduction tag. It has been shown to have broad-spectrum antiviral
      activity, but there have been no reports regarding its effect on PRRSV. Here, we
      demonstrate that DRACO exhibits robust antiviral activity against PRRSV infection
      by suppressing virus RNA and protein synthesis in both Marc-145 cells and porcine
      alveolar macrophages (PAMs). In addition, DRACO still exhibited strong anti-PRRSV
      activity when viral replication was enhanced by knockdown of interferon-induced
      protein with tetratricopeptide repeats 3 (IFIT3) in Marc-145 cells. Furthermore,
      in PAMs, DRACO was capable of inducing IL-6 expression and reducing Hsp70
      expression, which might contribute to the inhibition of PRRSV infection.
      Collectively, our results imply that DRACO holds promise as a novel anti-PRRSV
      therapeutic drug. 

PMID- 25772578
TI  - Erratum to: Outcomes of trastuzumab therapy in HER2-positive early breast cancer
      patients.

PMID- 25772579
TI  - Fetal critical aortic stenosis with natural improvement of hydrops fetalis due to
      spontaneous relief of severe restrictive atrial communication.
AB  - We describe a rare case of fetal critical aortic stenosis with spontaneous relief
      of severe restrictive atrial communication, resulting in complete resolution of
      hydrops fetalis in utero. Fetal ultrasonography showed hydrops fetalis caused by
      critical aortic stenosis with a severely restrictive foramen ovale and severe
      mitral regurgitation at 23 weeks of gestation. Hydrops fetalis, however,
      spontaneously resolved, showing an obvious increase of flow through the foramen
      ovale and pulmonary vein at 26 weeks of gestation. The neonate required balloon
      dilation of the aortic valve and balloon atrioseptostomy immediately after birth
      and also received bilateral pulmonary artery banding and arterial duct stenting 1
      week later. The patient was in good condition after conversion to biventricular
      circulation via Ross procedure at 8 months old. The present case suggests that
      atrioseptostomy as a fetal intervention may improve outcome in even a hydropic
      condition. 

PMID- 25772580
TI  - Abnormal magnetic field effects on electrogenerated chemiluminescence.
AB  - We report abnormal magnetic field effects on electrogenerated chemiluminescence
      (MFEECL) based on triplet emission from the Ru(bpy)3Cl2-TPrA electrochemical
      system: the appearance of MFEECL after magnetic field ceases. In early studies
      the normal MFEECL have been observed from electrochemical systems during the
      application of magnetic field. Here, the abnormal MFEECL suggest that the
      activated charge-transfer [Ru(bpy)3(3+) ... TPrA(*)] complexes may become
      magnetized in magnetic field and experience a long magnetic relaxation after
      removing magnetic field. Our analysis indicates that the magnetic relaxation can
      gradually increase the density of charge-transfer complexes within reaction
      region due to decayed magnetic interactions, leading to a positive component in
      the abnormal MFEECL. On the other hand, the magnetic relaxation facilitates an
      inverse conversion from triplets to singlets within charge-transfer complexes.
      The inverse triplet -> singlet conversion reduces the density of triplet light
      emitting states through charge-transfer complexes and gives rise to a negative
      component in the abnormal MFEECL. The combination of positive and negative
      components can essentially lead to a non-monotonic profile in the abnormal MFEECL
      after ceasing magnetic field. Nevertheless, our experimental studies may reveal
      un-usual magnetic behaviors with long magnetic relaxation from the activated
      charge-transfer [Ru(bpy)3(3+) ... TPrA(*)] complexes in solution at room
      temperature. 

PMID- 25772581
TI  - Lung cancer screening overdiagnosis: reports of overdiagnosis in screening for
      lung cancer are grossly exaggerated.
AB  - The National Lung Cancer Screening Trial (NLST) demonstrated a mortality
      reduction benefit associated with low-dose computed tomography (LDCT) screening
      for lung cancer. There has been considerable debate regarding the benefits and
      harms of LDCT lung cancer screening, including the challenges related to its
      practical implementation. One of the controversies regards overdiagnosis, which
      conceptually denotes diagnosing a cancer that, either because of its indolent,
      low-aggressiveness biologic behavior or because of limited life expectancy, is
      unlikely to result in significant morbidity during the patient's remainder
      lifetime. In theory, diagnosing and treating these cancers offer no measurable
      benefit while incurring costs and risks. Therefore, if a screening test detects a
      substantial number of overdiagnosed cancers, it is less likely to be effective.
      It has been argued that LDCT screening for lung cancer results in an unacceptably
      high rate of overdiagnosis. This article aims to defend the opposite stance.
      Overdiagnosis does exist and to a certain extent is inherent to any cancer
      screening test. Nonetheless, the concept is less dualistic and more nuanced than
      it has been suggested. Furthermore, the average estimates of overdiagnosis in
      LDCT lung cancer screening based on the totality of published data are likely
      much lower than the highest published estimates, if a careful definition of a
      positive screening test reflecting our current understanding of lung cancer
      biology is utilized. This article presents evidence on why reports of
      overdiagnosis in lung cancer screening have been exaggerated. 

PMID- 25772582
TI  - Iodine Distribution Map in Dual-Energy Computed Tomography Pulmonary Artery
      Imaging with Rapid kVp Switching for the Diagnostic Analysis and Quantitative
      Evaluation of Acute Pulmonary Embolism.
AB  - RATIONALE AND OBJECTIVES: To assess the diagnostic value of dual-energy (DE)
      computed tomography pulmonary angiography (CTPA) for acute pulmonary embolism
      (PE) using a helical DE scan mode with rapid kVp switching. MATERIALS AND
      METHODS: Seventy-six patients with suspected acute PE underwent DE CTPA. Two
      readers independently assessed and measured the iodine maps. CTPA images were
      assessed for the presence, location, and degree of PE as the standard of
      reference. Iodine maps were used to identify the perfusion defect (PD), and the
      diagnostic accuracy of iodine maps was calculated. The iodine concentrations of
      PDs and normal lung parenchyma were also measured and compared. RESULTS: A per
      patient analysis showed the 84.6% sensitivity and 96.0% specificity of iodine map
      for PE, and on per-segment analysis, the sensitivity and specificity for PE were
      82.9% and 99.6%, respectively. Intraobserver and interobserver variability
      correlations were excellent, with k values from 0.806 to 1.000. Quantitative
      analysis showed there was a significant difference for iodine concentration
      between circumscribed/patchy PDs or wedge-shaped PDs consistent with PE and
      normal lung parenchyma (P < .05). The intraobserver reliability of reader 1 was
      from 0.928 to 0.997, and reader 2 was from 0.912 to 0.995. And, the interobserver
      reliability between two readers was from 0.967 to 0.999. CONCLUSIONS: CTPA based
      on DE scanning with rapid kVp switching can provide both morphologic analysis and
      quantitative evaluation of PD related to acute PE in addition to standard CTPA
      data. Quantification of iodine concentration may be helpful for identifying the
      presence or absence of PE.

PMID- 25772583
TI  - Selective observation of the disordered import signal of a globular protein by in
      cell NMR: the example of frataxins.
AB  - We have exploited the capability of in-cell NMR to selectively observe flexible
      regions within folded proteins to carry out a comparative study of two members of
      the highly conserved frataxin family which are found both in prokaryotes and in
      eukaryotes. They all contain a globular domain which shares more than 50%
      identity, which in eukaryotes is preceded by an N-terminal tail containing the
      mitochondrial import signal. We demonstrate that the NMR spectrum of the
      bacterial ortholog CyaY cannot be observed in the homologous E. coli system,
      although it becomes fully observable as soon as the cells are lysed. This
      behavior has been observed for several other compact globular proteins as seems
      to be the rule rather than the exception. The NMR spectrum of the yeast ortholog
      Yfh1 contains instead visible signals from the protein. We demonstrate that they
      correspond to the flexible N-terminal tail indicating that this is flexible and
      unfolded. This flexibility of the N-terminus agrees with previous studies of
      human frataxin, despite the extensive sequence diversity of this region in the
      two proteins. Interestingly, the residues that we observe in in-cell experiments
      are not visible in the crystal structure of a Yfh1 mutant designed to destabilize
      the first helix. More importantly, our results show that, in cell, the protein is
      predominantly present not as an aggregate but as a monomeric species.

PMID- 25772584
TI  - The influence of immunosuppressants on the morphology, proliferating cell nuclear
      antigen (PCNA) and apoptosis in the rat ventral prostate.
AB  - AIM: Analysis of the impact of immunosuppressants on apoptosis and PCNA in the
      rat ventral prostate. METHOD: The studies were performed on 48 male Wistar rats.
      The animals were divided into a control group and 7 experimental groups. For 6
      months, the rats were administered drugs such as: rapamycin (Rapa), cyclosporin A
      (CsA), tacrolimus (Tac), mycophenolate mofetil (MMF) and glucocorticosteroids
      (GS). During section of the rats, prostate ventral lobes were obtained.
      Morphological evaluation (HE, PAS), TUNEL assay, PCNA expression analysis and
      quantitative image computer analysis were performed. RESULTS: The highest
      percentage of apoptosis in epithelial cells was observed in groups which received
      two combinations of drugs: (V) CsA, MMF, GS and (VII) Tac, MMF, GS. A much lower
      percentage of apoptotic epithelial cells was found in the groups where the
      treatment schemes included rapamycin throughout the duration of the study.
      Interestingly, the conversion of the treatment to rapamycin caused a significant
      reduction of apoptosis in epithelial cells as well as in proliferation in both
      epithelial and stromal cells. CONCLUSIONS: On one hand, the obtained results may
      explain the anticancer activity of rapamycin in reducing the proliferation of
      epithelial cells, and on the other hand the adverse effect of rapamycin in the
      form of reduced regeneration of these cells. Taking into account the prostate in
      isolation from other organs/systems, the dosage scheme with Rapa, Tac and GS
      would appear to be the most favorable, due to the smallest morphological changes.

PMID- 25772585
TI  - NICE draft type 2 diabetes guidelines: a cause for concern.

PMID- 25772586
TI  - Molecular mechanism of NDMA formation from N,N-dimethylsulfamide during
      ozonation: quantum chemical insights into a bromide-catalyzed pathway.
AB  - During ozonation of drinking water, the fungicide metabolite N,N
      dimethylsulfamide (DMS) can be transformed into a highly toxic product, N
      nitrosodimethylamine (NDMA). We used quantum chemical computations and stopped
      flow experiments to evaluate a chemical mechanism proposed previously to describe
      this transformation. Stopped-flow experiments indicate a pK(a) = 10.4 for DMS.
      Experiments show that hypobromous acid (HOBr), generated by ozone oxidation of
      naturally occurring bromide, brominates the deprotonated DMS(-) anion with a near
      diffusion controlled rate constant (7.1 +/- 0.6 * 10(8) M(-1) s(-1)), forming Br
      DMS(-) anion. According to quantum chemical calculations, Br-DMS has a pK(a) ~
      9.0 and thus remains partially deprotonated at neutral pH. The anionic Br-DMS(-)
      bromamine can react with ozone with a high rate constant (10(5 +/- 2.5) M(-1) s(
      1)), forming the reaction intermediate (BrNO)(SO2)N(CH3)2(-). This intermediate
      resembles a loosely bound complex between an electrophilic nitrosyl bromide
      (BrNO) molecule and an electron-rich dimethylaminosulfinate ((SO2)N(CH3)2(-))
      fragment, based on inspection of computed natural charges and geometric
      parameters. This fragile complex undergoes immediate (10(10 +/- 2.5) s(-1))
      reaction by two branches: an exothermic channel that produces NDMA, and an
      entropy-driven channel giving non-NDMA products. Computational results bring new
      insights into the electronic nature, chemical equilibria, and kinetics of the
      elementary reactions of this pathway, enabled by computed energies of structures
      that are not possible to access experimentally.

PMID- 25772587
TI  - The Effects of a Walking Exercise Program on Fatigue in the Person with COPD.
AB  - PURPOSE: The aim of the study was to assess the effect of a walking exercise
      program, three times a week for 8 weeks, on fatigue in people with chronic
      obstructive pulmonary disease (COPD). DESIGN: This study was a randomized
      controlled trial. METHODS: Walking exercise was applied to the intervention group
      three times a week for 8 weeks; no exercise was applied to the control group.
      FINDINGS: No difference was seen between the points of pretest fatigue of the
      intervention and control groups (t = -0.788, p = .434). However, according to the
      posttest, the intervention group's point of fatigue was lower than the control
      groups, and this difference was statistically significant (t = -3.924, p = .001).
      CONCLUSION: It was found that a walking exercise program applied to patients with
      COPD affected the fatigue symptom positively. CLINICAL RELEVANCE: Walking
      exercises programme can be used by nurses as a reference to monitor chronic
      obstructive pulmoner disease patients' health status.

PMID- 25772588
TI  - Investigation on cobalt-oxide nanoparticles cyto-genotoxicity and inflammatory
      response in two types of respiratory cells.
AB  - The increasing use of cobalt oxide (Co3 O4 ) nanoparticles (NPs) in several
      applications and the suggested genotoxic potential of Co-oxide highlight the
      importance of evaluating Co3 O4 NPs toxicity. Cyto-genotoxic and inflammatory
      effects induced by Co3 O4 NPs were investigated in human alveolar (A549), and
      bronchial (BEAS-2B) cells exposed to 1-40 ug ml(-1) . The physicochemical
      properties of tested NPs were analysed by transmission electron microscopy (TEM)
      and dynamic light scattering (DLS). Cytotoxicity was studied to analyze cell
      viability (WST1 test) and membrane damage (LDH assay), direct/oxidative DNA
      damage was assessed by the Formamido-pyrimidine glycosylase (Fpg)-modified comet
      assay and inflammation by interleukin (IL)-6, IL-8 and tumor necrosis factor
      alpha (TNF-alpha) release (ELISA). In A549 cells, no cytotoxicity was found,
      whereas BEAS-2B cells showed a viability reduction at 40 ug ml(-1) and early
      membrane damage at 1, 5 and 40 ug ml-1. In A549 cells, direct and oxidative DNA
      damage at 20 and 40 ug ml(-1) were detected without any effects on cytokine
      release. In BEAS-2B cells, significant direct DNA damage at 40 ug ml(-1) and
      significant oxidative DNA damage with a peak at 5 ug ml(-1) , that was associated
      with increased TNF-alpha release at 1 ug ml(-1) after 2 h and increased IL-8
      release at 20 ug ml(-1) after 24 h, were detected. The findings show in the
      transformed alveolar cells no cytotoxicity and genotoxic/oxidative effects at 20
      and 40 ug ml(-1) . In normal bronchial cells, moderate cytotoxicity, direct DNA
      damage only at the highest concentration and significant oxidative-inflammatory
      effects at lower concentrations were detected. The findings confirm the genotoxic
      oxidative potential of Co3 O4 NPs and show greater sensitivity of BEAS-2B cells
      to cytotoxic and oxidative-inflammatory effects suggesting the use of different
      cell lines and multiple end-points to elucidate Co3 O4 NPs toxicity.

PMID- 25772589
TI  - Linking the chemical speciation of cerium to its bioavailability in water for a
      freshwater alga.
AB  - Over the past decade, researchers have begun to use metals of the lanthanide
      family for numerous applications, including liquid crystal display (LCD) screens,
      optical fibers, and laser technology. Unfortunately, little is presently known
      about their bioavailability or the mechanisms by which they might cause toxicity.
      The present study focuses on cerium (Ce), one of the most widely used
      lanthanides, and on validating the biotic ligand model as a means to predict Ce
      bioaccumulation. Short-term exposures to Ce were performed using the unicellular
      alga Chlamydomonas reinhardtii, to better relate Ce bioavailability to its
      chemical speciation in solution. Maximum uptake fluxes (Jmax ) and affinity
      constants for the binding of Ce to the biological uptake sites (KS ) were
      established at pH 5.0 and pH 7.0. An apparent affinity constant of 1.8 * 10(7) M(
      1) was observed at pH 5.0, with a larger value obtained at pH 7.0 (6 * 10(7) M(
      1) ), albeit under conditions where equilibrium could not be confirmed. By
      evaluating Ce speciation using centrifugal ultrafiltration and single-particle
      inductively coupled plasma spectrometry, it could be concluded that very little
      (~30%) Ce was truly dissolved at pH 7.0, with the majority of the metal being
      present in colloidal species. Speciation was also monitored by fluorescence to
      evaluate Ce complexation by natural organic matter (NOM). The presence of NOM
      decreased Ce bioaccumulation in line with free Ce concentrations. Finally,
      competition with calcium for the metal uptake sites was shown to result in a
      decrease in Ce uptake by C. reinhardtii.

PMID- 25772590
TI  - Innovative clinical trials for development of personalized cancer medicine.

PMID- 25772591
TI  - Surgical results for recurrent hepatocellular carcinoma after curative
      hepatectomy: Repeat hepatectomy versus salvage living donor liver
      transplantation.
AB  - The aims of this study were to evaluate the efficacy of repeat hepatectomy (Hx)
      and salvage living donor liver transplantation (LDLT) for recurrent
      hepatocellular carcinoma (HCC). A retrospective cohort study was performed to
      analyze the surgical results of repeat Hx and salvage LDLT for patients with
      recurrent HCC within the Milan criteria from 1989 to 2012. A total of 159
      patients were divided into 2 groups: a repeat Hx group (n = 146) and a salvage
      LDLT group (n = 13). Operative results and patient prognoses were compared
      between the 2 groups. The operative invasiveness, including the operation time
      (229.1 +/- 97.7 versus 862.9 +/- 194.4 minutes; P < 0.0001) and blood loss (596.3
      +/- 764.9 versus 24,690 +/- 59,014.4 g; P < 0.0001), were significantly higher in
      the salvage LDLT group. The early surgical results, such as morbidity (31% versus
      62%; P = 0.0111) and the duration of hospital stay (20 +/- 22 versus 35 +/- 21
      days; P = 0.0180), were significantly worse in the salvage LDLT group. There was
      no significant difference in the overall survival (OS) rate, but the disease-free
      survival rate of the salvage LDLT group was significantly better (P = 0.0002).
      The OS rate of patients with grade B liver damage in the repeat Hx group was
      significantly worse (P < 0.0001), and the 5-year OS rate was quite low, that is,
      20% (liver damage A, 77% for the repeat Hx group and 75% for the salvage LDLT
      group). The prognosis of patients with grade B liver damage after repeat Hx for
      recurrent HCC is poor, and salvage LDLT would be a potent option for such
      patients.

PMID- 25772592
TI  - The other side of asthma: Steroid-refractory disease in the absence of TH2
      mediated inflammation.

PMID- 25772593
TI  - Hazelnut allergy across Europe dissected molecularly: A EuroPrevall outpatient
      clinic survey.
AB  - BACKGROUND: Hazelnut allergy is birch pollen-driven in Northern/Western Europe
      and lipid transfer protein-driven in Spain and Italy. Little is known about other
      regions and other allergens. OBJECTIVE: Establishing a molecular map of hazelnut
      allergy across Europe. METHODS: In 12 European cities, subjects reporting
      reactions to hazelnut (n = 731) were evaluated and sensitization to 24 foods, 12
      respiratory allergen sources, and latex was tested by using skin prick test and
      ImmunoCAP. A subset (124 of 731) underwent a double-blind placebo-controlled food
      challenge to hazelnut. Sera of 423 of 731 subjects were analyzed for IgE against
      7 hazelnut allergens and cross-reactive carbohydrate determinants by ImmunoCAP.
      RESULTS: Hazelnut allergy was confirmed in 70% of those undergoing double-blind
      placebo-controlled food challenges. Birch pollen-driven hazelnut sensitization
      (Cor a 1) dominated in most cities, except in Reykjavik, Sofia, Athens, and
      Madrid, where reporting of hazelnut allergy was less frequent anyhow. In Athens,
      IgE against Cor a 8 dominated and strongly correlated with IgE against walnut,
      peach, and apple and against Chenopodium, plane tree, and mugwort pollen.
      Sensitization to seed storage proteins was observed in less than 10%, mainly in
      children, and correlated with IgE to nuts, seeds, and legumes. IgE to Cor a 12,
      observed in all cities (10% to 25%), correlated with IgE to nuts, seeds, and
      pollen. CONCLUSIONS: In adulthood, the importance of hazelnut sensitization to
      storage proteins, oleosin (Cor a 12), and Cor a 8 is diluted by the increased
      role of birch pollen cross-reactivity with Cor a 1. Cor a 8 sensitization in the
      Mediterranean is probably driven by diet in combination with pollen exposure.
      Hazelnut oleosin sensitization is prevalent across Europe; however, the clinical
      relevance remains to be established.

PMID- 25772595
TI  - MicroRNA-9 regulates steroid-resistant airway hyperresponsiveness by reducing
      protein phosphatase 2A activity.
AB  - BACKGROUND: Steroid-resistant asthma is a major clinical problem that is linked
      to activation of innate immune cells. Levels of IFN-gamma and LPS are often
      increased in these patients. Cooperative signaling between IFN-gamma/LPS induces
      macrophage-dependent steroid-resistant airway hyperresponsiveness (AHR) in mouse
      models. MicroRNAs (miRs) are small noncoding RNAs that regulate the function of
      innate immune cells by controlling mRNA stability and translation. Their role in
      regulating glucocorticoid responsiveness and AHR remains unexplored. OBJECTIVE:
      IFN-gamma and LPS synergistically increase the expression of miR-9 in macrophages
      and lung tissue, suggesting a role in the mechanisms of steroid resistance. Here
      we demonstrate the role of miR-9 in IFN-gamma/LPS-induced inhibition of
      dexamethasone (DEX) signaling in macrophages and in induction of steroid
      resistant AHR. METHODS: MiRNA-9 expression was assessed by means of quantitative
      RT-PCR. Putative miR-9 targets were determined in silico and confirmed in
      luciferase reporter assays. miR-9 function was inhibited with sequence-specific
      antagomirs. The efficacy of DEX was assessed by quantifying glucocorticoid
      receptor (GR) cellular localization, protein phosphatase 2A (PP2A) activity, and
      AHR. RESULTS: Exposure of pulmonary macrophages to IFN-gamma/LPS synergistically
      induced miR-9 expression; reduced levels of its target transcript, protein
      phosphatase 2 regulatory subunit B (B56) delta isoform; attenuated PP2A activity;
      and inhibited DEX-induced GR nuclear translocation. Inhibition of miR-9 increased
      both PP2A activity and GR nuclear translocation in macrophages and restored
      steroid sensitivity in multiple models of steroid-resistant AHR. Pharmacologic
      activation of PP2A restored DEX efficacy and inhibited AHR. MiR-9 expression was
      increased in sputum of patients with neutrophilic but not those with eosinophilic
      asthma. CONCLUSION: MiR-9 regulates GR signaling and steroid-resistant AHR.
      Targeting miR-9 function might be a novel approach for the treatment of steroid
      resistant asthma.

PMID- 25772596
TI  - The influence of asthma control on the severity of virus-induced asthma
      exacerbations.

PMID- 25772594
TI  - Distinct endotypes of steroid-resistant asthma characterized by IL-17A(high) and
      IFN-gamma(high) immunophenotypes: Potential benefits of calcitriol.
AB  - BACKGROUND: A small population of patients with severe asthma does not respond to
      glucocorticoids (steroid resistant [SR]). They have high morbidity, highlighting
      an urgent need for strategies to enhance glucocorticoid responsiveness.
      OBJECTIVE: We investigated the immunologic differences between steroid-sensitive
      (SS) and SR asthmatic patients and the effect on immunophenotype of oral
      calcitriol treatment because it has been previously shown to beneficially
      modulate the clinical response to glucocorticoids in patients with SR asthma.
      METHODS: CD8-depleted PBMCs were isolated from 12 patients with SS and 23
      patients with SR asthma and cultured for 7 days with anti-CD3 and IL-2 with or
      without dexamethasone. Cytokine production was assessed in supernatants by using
      the Cytometric Bead Array. Patients with SR asthma were subsequently randomized
      to oral calcitriol or placebo therapy, and identical studies were repeated.
      RESULTS: Patients with SR asthma produced significantly increased IL-17A and IFN
      gamma levels compared with those in patients with SS asthma, although it was
      evident that cells from individual patients might overproduce one or the other of
      these cytokines. Production of IL-17A was inversely and production of IL-13 was
      positively associated with the clinical response to prednisolone. Oral
      calcitriol, compared with placebo, therapy of the patients with SR asthma
      significantly improved dexamethasone-induced IL-10 production in vitro while
      suppressing dexamethasone-induced IL-17A production. This effect mirrored the
      previously demonstrated improvement in clinical response to oral glucocorticoids
      in calcitriol-treated patients with SR asthma. CONCLUSIONS: IL-17A(high) and IFN
      gamma(high) immunophenotypes exist in patients with SR asthma. These data
      identify immunologic pathways that likely underpin the beneficial clinical
      effects of calcitriol in patients with SR asthma by directing the SR cytokine
      profile toward a more SS immune phenotype, suggesting strategies for identifying
      vitamin D responder immunophenotypes.

PMID- 25772598
TI  - Custodial Homes, Therapeutic Homes, and Parental Acceptance: Parental Experiences
      of Autism in Kerala, India and Atlanta, GA USA.
AB  - The home is a critical place to learn about cultural values of childhood
      disability, including autism and intellectual disabilities. The current article
      describes how the introduction of autism into a home and the availability of
      intervention options change the structure and meaning of a home and reflect
      parental acceptance of a child's autistic traits. Using ethnographic data from
      Kerala, India and Atlanta, GA USA, a description of two types of homes are
      developed: the custodial home, which is primarily focused on caring for basic
      needs, and the therapeutic home, which is focused on changing a child's autistic
      traits. The type of home environment is respondent to cultural practices of child
      rearing in the home and influences daily activities, management, and care in the
      home. Further, these homes differ in parental acceptance of their autistic
      children's disabilities, which is critical to understand when engaging in
      international work related to autism and intellectual disability. It is proposed
      that parental acceptance can be fostered through the use of neurodiverse notions
      that encourage autism acceptance. 

PMID- 25772599
TI  - Impact of IgG3 subclass and C1q-fixing donor-specific HLA alloantibodies on
      rejection and survival in liver transplantation.
AB  - Recent literature confirms donor-specific HLA alloantibodies (DSA) impair 5-year
      survival in some but not all liver transplant recipients. In an effort to improve
      DSA testing's association with rejection and death, we retrospectively evaluated
      1270 liver transplant recipients for the presence of IgG3 and C1q-fixing DSA. In
      patients with preformed DSA, 29 and 51% had IgG3 and C1q-fixing DSA,
      respectively. In patients with de novo DSA, 62% and 67% had IgG3 and C1q-fixing
      DSA, respectively. When different types of DSA positive patients were compared to
      DSA negative patients, multivariable analysis showed that IgG3 DSA positivity had
      the highest numerical hazard ratio for death (IgG3: HR = 2.4, p < 0.001; C1q: HR
      = 1.9, p < 0.001; standard DSA: HR = 1.6, p < 0.001). Similarly, multivariable
      analysis demonstrated de novo IgG3 DSA positivity compared to no DSA had the
      highest hazard ratio for death (IgG3: HR = 2.1, p = 0.004; C1q: HR = 1.9, p =
      0.02; standard DSA: HR = 1.8, p = 0.007). Preformed C1q-fixing class II DSA
      showed the strongest correlation with early rejection. In conclusion, preformed
      and de novo IgG3 subclass DSA positive patients had the highest absolute HR for
      death in side-by-side comparison with C1q and standard DSA positive versus DSA
      negative patients; however, IgG3 negative DSA positive patients still had
      inferior outcomes compared to DSA negative patients. 

PMID- 25772597
TI  - Jug r 2-reactive CD4(+) T cells have a dominant immune role in walnut allergy.
AB  - BACKGROUND: Allergic reactions to walnut can be life-threatening. Although IgE
      epitopes of walnut have been studied, CD4(+) T cell-specific epitopes for walnut
      remain uncharacterized. In particular, the relationship of both phenotype and
      frequency of walnut-specific T cells to the disease have not been examined.
      OBJECTIVES: We sought to provide a thorough phenotypic analysis for walnut
      reactive T cells in allergic and nonallergic subjects, particularly the
      relationship of phenotypes and frequencies of walnut-specific T cells with the
      disease. METHODS: The CD154 upregulation assay was used to examine CD4(+) T-cell
      reactivity toward the walnut allergens Jug r 1, Jug r 2, and Jug r 3. A tetramer
      guided epitope mapping approach was used to identify HLA-restricted CD4(+) T-cell
      epitopes in Jug r 2. Direct ex vivo staining with peptide-major
      histocompatibility complex class II tetramers enabled comparison of the frequency
      and phenotype of Jug r 2-specific CD4(+) T cells between allergic and nonallergic
      subjects. Jug r 2-specific T-cell clones were also generated, and mRNA
      transcription factor levels were assessed by using quantitative RT-PCR.
      Intracellular cytokine staining assays were performed for further phenotypic
      analyses. RESULTS: Jug r 2 was identified as the major allergen that elicited
      CD4(+) T-cell responses. Multiple Jug r 2 T-cell epitopes were identified. The
      majority of these T cells in allergic subjects have a CCR4(+) phenotype. A subset
      of these T cells express CCR4(+)CCR6(+) irrespective of the asthmatic status of
      the allergic subjects. Intracellular cytokine staining confirmed these TH2-,
      TH2/TH17-, and TH17-like heterogenic profiles. Jug r 2-specific T-cell clones
      from allergic subjects mainly expressed GATA3, nonetheless, a portion of T-cell
      clones both GATA3 and RAR-related orphan receptor C (RORC) or RORC alone,
      confirming the presence of TH2, TH2/TH17, and TH17 cells. CONCLUSIONS: Jug r 2
      specific responses dominate walnut T-cell responses in patients with walnut
      allergy. Jug r 2 central memory CD4(+) cells and terminal effector T cells were
      detected in peripheral blood, with the central memory phenotype as the most
      prevalent phenotype. In addition to conventional TH2 cells, TH2/TH17 and TH17
      cells were also detected in nonasthmatic and asthmatic patients with walnut
      allergy. Understanding this T-cell heterogeneity might render better
      understanding of the disease manifestation.

PMID- 25772600
TI  - An efficient one-pot four-segment condensation method for protein chemical
      synthesis.
AB  - Successive peptide ligation using a one-pot method can improve the efficiency of
      protein chemical synthesis. Although one-pot three-segment ligation has enjoyed
      widespread application, a robust method for one-pot four-segment ligation had to
      date remained undeveloped. Herein we report a new one-pot multisegment peptide
      ligation method that can be used to condense up to four segments with operational
      simplicity and high efficiency. Its practicality is demonstrated by the one-pot
      four-segment synthesis of a plant protein, crambin, and a human chemokine,
      hCCL21. 

PMID- 25772601
TI  - The Effect of Radiation on Complication Rates and Patient Satisfaction in Breast
      Reconstruction using Temporary Tissue Expanders and Permanent Implants.
AB  - The optimal method of reconstruction following mastectomy for breast cancer
      patients receiving radiation therapy (RT) is controversial. This study evaluated
      patient satisfaction and complication rates among patients who received implant
      based breast reconstruction. The specific treatment algorithm analyzed included
      patients receiving mastectomy and immediate temporary tissue expander (TE),
      followed by placement of a permanent breast implant (PI). If indicated, RT was
      delivered to the fully expanded TE. Records of 218 consecutive patients with 222
      invasive (85%) or in situ (15%) breast lesions from the Salt Lake City region
      treated between 1998 and 2009 were retrospectively reviewed, 28% of whom received
      RT. Median RT dose was 50.4 Gy, and 41% received a scar boost at a median dose of
      10 Gy. Kaplan-Meier analyses were performed to evaluate the cumulative incidence
      of surgical complications, including permanent PI removal. Risk factors
      associated with surgical events were analyzed. To evaluate cosmetic results and
      patient satisfaction, an anonymous survey was administered. Mean follow-up was 44
      months (range 6-144). Actuarial 5-year PI removal rates for non-RT and RT
      patients were 4% and 22%, respectively. On multivariate analysis (MVA), the only
      factor associated with PI removal was RT (p = 0.009). Surveys were returned
      describing the outcomes of 149 breasts. For the non-RT and RT groups, those who
      rated their breast appearance as good or better were 63% versus 62%,
      respectively. Under 1/3 of each group was dissatisfied with their reconstruction.
      RT did not significantly affect patient satisfaction scores, but on MVA RT was
      the only factor associated with increased PI removal. This reconstruction
      technique may be considered an acceptable option even if RT is needed, but the
      increased complication risk with RT must be recognized.

PMID- 25772602
TI  - Phonological simplifications, apraxia of speech and the interaction between
      phonological and phonetic processing.
AB  - Research on aphasia has struggled to identify apraxia of speech (AoS) as an
      independent deficit affecting a processing level separate from phonological
      assembly and motor implementation. This is because AoS is characterized by both
      phonological and phonetic errors and, therefore, can be interpreted as a
      combination of deficits at the phonological and the motoric level rather than as
      an independent impairment. We apply novel psycholinguistic analyses to the
      perceptually phonological errors made by 24 Italian aphasic patients. We show
      that only patients with relative high rate (>10%) of phonetic errors make sound
      errors which simplify the phonology of the target. Moreover, simplifications are
      strongly associated with other variables indicative of articulatory difficulties 
      such as a predominance of errors on consonants rather than vowels - but not with
      other measures - such as rate of words reproduced correctly or rates of lexical
      errors. These results indicate that sound errors cannot arise at a single
      phonological level because they are different in different patients. Instead,
      different patterns: (1) provide evidence for separate impairments and the
      existence of a level of articulatory planning/programming intermediate between
      phonological selection and motor implementation; (2) validate AoS as an
      independent impairment at this level, characterized by phonetic errors and
      phonological simplifications; (3) support the claim that linguistic principles of
      complexity have an articulatory basis since they only apply in patients with
      associated articulatory difficulties. 

PMID- 25772603
TI  - Dissociation of explicit and implicit responses during a change blindness task in
      schizophrenia.
AB  - BACKGROUND: Patients with schizophrenia are abnormally disturbed by information
      onsets, which may result in a disadvantage in filtering relevant information. The
      paradigm of change blindness offers the interesting possibility of studying
      sensitivity to the sudden irruption of visual information with ecological stimuli
      in schizophrenia. An increased attentional capture by the irruption of visual
      information would suggest better performance in patients than in healthy
      controls. This approach has the advantage of circumventing a non-specific general
      attentional deficit in schizophrenia. METHODS: Sixteen patients with
      schizophrenia and 16 healthy controls were asked to detect changes in 99 scenes
      with 0, 1 or 3 changes. We measured the participants' speed and accuracy in
      explicitly reporting the changes via motor responses and their capacity to
      implicitly detect changes via eye movements. RESULTS: Although the controls were
      faster and more efficient in explicitly reporting changes, the patients' eyes
      shifted more quickly toward the changes. Regardless of the group, increasing the
      magnitude of change improved the performance. CONCLUSIONS: The better capacity of
      the patients to shift their eyes toward changes confirmed the capture by the
      sudden irruption of visual information in schizophrenia while avoiding the
      effects of general attentional deficits. However, the striking dissociation
      between this implicit response and the capacity to explicitly report changes
      could be interpreted as a deficit in access to conscious perception.

PMID- 25772604
TI  - [Current capabilities of telemedicine in anaesthesiology].
AB  - Because of an ageing population and a relative lack of professionals, the German
      health system is under great pressure. In rural regions in particular,
      anesthesiology is also affected - nursing staff, anesthetists, intensive care
      physicians, and emergency physicians often have to be supported by freelancers
      from other regions and from abroad - at least periodically. In addition to the
      increasing number of treatments, the potential quality of therapy is also
      increasing owing to progress in medical research. Against this background the
      need for resources is increasing to ensure the optimal quality of treatment. This
      applies to all clinical disciplines, including all sections of anesthesiology -
      especially in economically underdeveloped regions where highly qualified experts
      are lacking. In various cases it is not the physical attendance or manual skills
      of experts that is primarily requested on-site, but rather their medical
      expertise and experience. Therefore, telemedicine systems are suitable for
      closing these gaps very effectively and efficiently. In the various
      anesthesiological sub-sections the number of scientific papers published to date
      varies. For anesthesia and pain therapy only a few telemedical applications or
      concepts have been reported in the literature. However, in tele-intensive care
      medicine and tele-emergency medicine several national and international research
      projects have successfully been carried out, leading to established routine
      systems in some cases. 

PMID- 25772605
TI  - Identification of four Aconitum species used as "Caowu" in herbal markets by 3D
      reconstruction and microstructural comparison.
AB  - Authentication is the first priority when evaluating the quality of Chinese
      herbal medicines, particularly highly toxic medicines. The most commonly used
      authentication methods are morphological identification and microscopic
      identification. Unfortunately, these methods could not effectively evaluate some
      herbs with complex interior structures, such as root of Aconitum species with a
      circular conical shape and an interior structure with successive changes.
      Defining the part that should be selected as the standard plays an essential role
      in accurate microscopic identification. In this study, we first present a visual
      3D model of Aconitum carmichaeli Debx. constructed obtained from microscopic
      analysis of serial sections. Based on this model, we concluded that the point of
      largest root diameter should be used as the standard for comparison and
      identification. The interior structure at this point is reproducible and its
      shape and appearance can easily be used to distinguish among species. We also
      report details of the interior structures of parts not shown in the 3D model,
      such as stone cells and cortical thickness. To demonstrate the usefulness of the
      results from the 3D model, we have distinguished the microscopic structures, at
      their largest segments, of the other three Aconitum species used for local
      habitat species of Caowu. This work provides the basis for resolution of some
      debate regarding the microstructural differences among these species. Thus, we
      conclude that the 3D model composed of serial sections has enabled the selection
      of a standard cross-section that will enable the accurate identification of
      Aconitum species in Chinese medicine.

PMID- 25772606
TI  - Magnetic bubblecade memory based on chiral domain walls.
AB  - Unidirectional motion of magnetic domain walls is the key concept underlying next
      generation domain-wall-mediated memory and logic devices. Such motion has been
      achieved either by injecting large electric currents into nanowires or by
      employing domain-wall tension induced by sophisticated structural modulation.
      Herein, we demonstrate a new scheme without any current injection or structural
      modulation. This scheme utilizes the recently discovered chiral domain walls,
      which exhibit asymmetry in their speed with respect to magnetic fields. Because
      of this asymmetry, an alternating magnetic field results in the coherent motion
      of the domain walls in one direction. Such coherent unidirectional motion is
      achieved even for an array of magnetic bubble domains, enabling the design of a
      new device prototype-magnetic bubblecade memory-with two-dimensional data-storage
      capability. 

PMID- 25772607
TI  - Augmented, Reality-Enhanced Navigation for Extracranial-Intracranial Bypass.

PMID- 25772609
TI  - Surgery Versus Radiation Therapy Alone in Treating Spinal Metastasis: A
      Perspective.

PMID- 25772610
TI  - Third Ventriculocisternostomy for Shunt Failure.
AB  - BACKGROUND: Our objective was to analyze the relevance, potential prognostic
      factors, and complications of endoscopic third ventriculostomy (ETV) in patients
      with shunt failures. METHODS: Among 721 ETVs performed between 1999 and 2013, we
      studied 53 patients with shunts (31 men, 21 less than 18 years of age) who had an
      ETV performed for shunt failures as the result of various causes. We included all
      initial causes of hydrocephalus except adult chronic (i.e., "normal pressure")
      and pediatric communicant hydrocephalus. The mean duration between initial
      shunting for hydrocephalus and the ETV procedure was more than 11 years (137
      months; range, 1 month to 34 years). Successful ETV procedure was defined as
      clinical improvement and shunt independence extending until the last follow-up
      visit. RESULTS: The success rate of the ETV procedure was 70% (37 of the 53
      cases) with a mean follow-up of 51 months (from 3 to 157 months) and was not
      related to the age of the patient (P = 0.922), to the cause of hydrocephalus (P =
      0.622), or to the number of shunt failures (P = 0.459). We also found no
      statistical difference (P = 0.343) between patients whose shunt had been in place
      for less than 5 years and those shunted more than 5 years. The presence of an
      infected shunt was not predictive of ETV failure (P = 0.395). No significant
      intraoperative or postoperative complications were noted. CONCLUSION: This study
      confirms that ETV should be considered as the first therapeutic option before
      shunt revision in cases of initial obstructive hydrocephalus.

PMID- 25772608
TI  - Early Cerebral Blood Volume Changes Predict Progression After Convection-Enhanced
      Delivery of Topotecan for Recurrent Malignant Glioma.
AB  - OBJECTIVE: To assess whether early changes in enhancing tumor volume (eTV) and
      relative cerebral blood volume (rCBV) 1 month after convection-enhanced delivery
      of topotecan in patients with recurrent malignant glioma correlated with 6-month
      disease progression status. METHODS: Sixteen patients were enrolled in a Phase Ib
      trial of convection-enhanced delivery of topotecan for recurrent malignant
      glioma. Each patient was evaluated with serial follow-up magnetic resonance
      imaging at baseline and at 4- to 8-week intervals. Changes at 1 month compared
      with baseline in eTV and rCBV were evaluated as potential predictors of 6-month
      progression status, classified as either progressive disease or nonprogressive
      disease. Relationships between percent changes in eTV and rCBV at 1 month with
      the probability of progressive disease at 6 months were estimated by the use of
      logistic regression analysis. Receiver operating characteristic curves for
      varying percent change thresholds in eTV and rCBV were evaluated by the use of 6
      month progressive disease as the reference. RESULTS: There was a significant
      difference in the percent change in rCBV at 1 month in patients with progressive
      disease compared with those with nonprogressive disease at 6 months (+12% vs. 
      29%, P = 0.02). Logistic regression analysis demonstrated on average that a 10%
      increase in rCBV at 1 month after convection-enhanced delivery of topotecan was
      associated with 1.7 times the odds of developing progressive disease at 6 months
      (95% confidence interval [CI] 1.0-2.9 P = 0.05). Receiver operating
      characteristic analysis for determining progressive disease at 6 months showed a
      greater area under the curve with rCBV (0.867; 95% CI 0.66-1.00) than with change
      in enhancing tumor volume (0.767; 95% CI 0.51-1.00). CONCLUSION: In this selected
      population of patients with recurrent malignant glioma treated with convection
      enhanced delivery of topotecan, early changes in rCBV at 4 weeks after therapy
      may help predict progression status at 6 months.

PMID- 25772611
TI  - Spinal Traumas and their Treatments According to Avicenna's Canon of Medicine.
AB  - Spinal Traumas have been categorized as disabling diseases that cause
      irretrievable personal and social problems. Having conducted a rather
      comprehensive diagnosis of the anatomy of the backbone and spinal cord as well as
      their functions, Avicenna (Ibn Sina, 980-1037) stated the levels and kinds of
      spinal impairments that are caused by spinal traumas in his great masterpiece Al
      Qanun fi al-Tibb (The Canon of Medicine). He also based his treatment process on
      his etiological diagnosis of such impairments. Avicenna had used the following
      methods to treat spinal traumas: food and drug therapy and regimental therapies
      such as massage, phlebotomy, cupping, dry sauna, and surgery. The authors of the
      present article review the bases of Avicenna's viewpoints regarding spinal
      traumas and their treatment. 

PMID- 25772613
TI  - Modification of the catalytic properties of the Au4 nanocluster for the
      conversion of methane-to-methanol: synergistic effects of metallic adatoms and a
      defective graphene support.
AB  - Decorating graphene with nano-clusters offers potential for a wide range of
      industrial applications. For catalysis, embedding precisely controlled mono- and
      bimetallic nanoclusters into graphene can greatly increase their catalytic
      activities, especially for oxidation reactions. The catalytic performance of a
      gold nanocluster can be modified dramatically by changing its electronic
      properties. The results of this work demonstrate by means of DFT calculations
      that by strategic doping and promotion from the support material the catalytic
      activity improvement of a gold-based catalyst for the partial oxidation reaction
      of methane can be drastically enhanced. The transition metal-mediated catalysis
      is significantly affected by the two spin-state reactivities over them. The
      investigated catalytic processes consist of N2O decomposition and methane
      hydroxylation over three subnanoclusters (Au5, Au4Pd, and Au4Pt) deposited on a
      single vacancy graphene support. It was found that graphene acts not only as a
      support but also supports the catalysis through charge transfer between the
      subnanocluster and graphene. Graphene-supported Au4Pd exhibits enhanced catalytic
      activity for both steps of methane-to-methanol conversion, whereas the supported
      Au5 is good for N2O decomposition but ineffective for methane hydroxylation,
      mainly due to the involvement of a very stable intermediate (methyl-hydroxo
      grafted nanocluster). The activation energies for N2O decomposition, C-H bond
      activation and methanol formation over the supported Au4Pd cluster are 13.8,
      15.7, and 24.9 kcal mol(-1), respectively. Without the graphene support, the
      catalytic trend is reversed and Au4Pd becomes an inert cluster for these
      reactions. 

PMID- 25772612
TI  - Nonmotor symptoms in subjects without evidence of dopaminergic deficits.
AB  - BACKGROUND: A subgroup of patients initially diagnosed with Parkinson's disease
      (PD) turn out to have normal dopamine transporter single-photon emission computed
      tomography imaging and have been labeled as subjects without evidence of
      dopaminergic deficit (SWEDDs). In this study, we sought to further characterize
      these patients and have analyzed the frequency of nonmotor symptoms (NMS) in
      SWEDDs, PD patients, and healthy controls. METHODS: We analyzed the baseline
      clinical data of 412 PD patients, 184 controls, and 62 SWEDDs included in the
      Parkinson's Progression Marker Initiative study on a variety of different NMS
      questionnaires. RESULTS: Both PD patients and SWEDDs had greater frequency of NMS
      than healthy controls. Furthermore, some NMS, such as orthostatic hypotension as
      well as cardiovascular and thermoregulatory dysfunction were even more commonly
      reported in SWEDDs than in PD patients, whereas hyposmia was more common in PD,
      compared to SWEDDs. CONCLUSION: NMS are more frequent in SWEDDs than in controls,
      and autonomic dysfunction and orthostatic hypotension were even more common than
      in PD patients. These findings support the notion that SWEDDS represent a group
      of patients with still poorly understood pathophysiology. (c) 2015 International
      Parkinson and Movement Disorder Society.

PMID- 25772614
TI  - Position detection and observation of a conducting filament hidden under a top
      electrode in a Ta2O5-based atomic switch.
AB  - Resistive random access memories (ReRAMs) are promising next-generation memory
      devices. Observation of the conductive filaments formed in ReRAMs is essential in
      understanding their operating mechanisms and their expected ultimate performance.
      Finding the position of the conductive filament is the key process in the
      preparation of samples for cross-sectional transmission electron microscopy (TEM)
      imaging. Here, we propose a method for locating the position of conductive
      filaments hidden under top electrodes. Atomic force microscopy imaging with a
      conductive tip detects the current flowing through a conductive filament from the
      bottom electrode, which reaches its maximum at a position that is above the
      conductive filament. This is achieved by properly biasing a top electrode, a
      bottom electrode and the conductive tip. This technique was applied to
      Cu/Ta2O5/Pt atomic switches, revealing the formation of a single Cu filament in a
      device, although the device had a large area of 5 * 5 MUm(2). Change in filament
      size was clearly observed depending on the compliance current used in the set
      process. It was also found from the TEM observation that the cross-sectional
      shape of the formed filament varies considerably, which is attributable to
      different Cu nuclei growth mechanisms. 

PMID- 25772615
TI  - Superficial acral fibromyxoma.
AB  - Superficial acral fibromyxoma (SAF), also known as digital fibromyxoma, is a rare
      soft tissue tumor with a predilection for acral surfaces. Superficial acral
      fibromyxoma classically presents as a pink to flesh-colored nodule located on the
      subungual or periungual region of the hands or feet. It is typically slow-growing
      and asymptomatic, which, coupled with its nonspecific clinical appearance,
      presents a diagnostic dilemma to the dermatologist. As these features overlap
      with those of a multitude of differential diagnoses, it is imperative to have a
      good understanding of the characteristics on which the diagnosis of SAF is based.
      Superficial acral fibromyxoma was initially described in 2001, since when several
      case reports and literature reviews have contributed to our current understanding
      of these tumors. In this article, we will review the history, clinical features,
      diagnosis, and management of SAF. It is our hope that this systematic approach
      will help to facilitate the recognition and management of this distinct
      dermatologic entity. 

PMID- 25772616
TI  - Golgi polarization plays a role in the directional migration of neonatal dermal
      fibroblasts induced by the direct current electric fields.
AB  - Directional cell migration requires cell polarization. The reorganization of the
      Golgi apparatus is an important phenomenon in the polarization and migration of
      many types of cells. Direct current electric fields (dc (EF) induced directional
      cell migration in a wide variety of cells. Here nHDFs migrated toward cathode
      under 1 V/cm dc EF, however 1 MUM of brefeldin A (BFA) inhibited the dc EF
      induced directional migration. BFA (1 MUM) did not cause the complete Golgi
      dispersal for 2 h. When the Golgi polarization maintained their direction of
      polarity, the direction of cell migration also kept toward the same direction of
      the Golgi polarization even though the dc EF was reversed. In this study, the
      importance of the Golgi polarization in the directional migration of nHDf under
      dc EF was identified.

PMID- 25772617
TI  - An RNautophagy/DNautophagy receptor, LAMP2C, possesses an arginine-rich motif
      that mediates RNA/DNA-binding.
AB  - Lysosomes are sites for the degradation of diverse cellular components. We
      recently discovered novel lysosomal systems we termed RNautophagy and
      DNautophagy. In these systems, RNA and DNA, respectively, are directly imported
      into lysosomes and degraded. A lysosomal membrane protein, LAMP2C was identified
      as a receptor for these pathways. The short C-terminal cytosolic tail of LAMP2C
      binds directly to both RNA and DNA. In this study, we examined the mechanisms
      underlying recognition of nucleic acids by the cytosolic sequence of LAMP2C. We
      found that the sequence possesses features of the arginine-rich motif, an RNA
      recognition motif found in a wide range of RNA-binding proteins. Substitution of
      arginine residues in the LAMP2C cytosolic sequence completely abolished its
      binding capacity for nucleic acids. A scrambled form of the sequence showed
      affinity to RNA and DNA equivalent to that of the wild-type sequence, as is the
      case for other arginine-rich motifs. We also found that cytosolic sequences of
      other LAMP family proteins, LAMP1 and CD68/LAMP4, also possess arginine residues,
      and show affinity for nucleic acids. Our results provide further insight into the
      mechanisms underlying RNautophagy and DNautophagy, and may contribute to a better
      understanding of lysosome function. 

PMID- 25772618
TI  - A novel helper phage for HaloTag-mediated co-display of enzyme and substrate on
      phage.
AB  - Phage display is an established technique for the molecular evolution of peptides
      and proteins. For the selection of enzymes based on catalytic activity however,
      simultaneous coupling of an enzyme and its substrate to the phage surface is
      required. To facilitate this process of co-display, we developed a new helper
      phage displaying HaloTag, a modified haloalkane dehalogenase that binds
      specifically and covalently to functionalized haloalkane ligands. The display of
      functional HaloTag was demonstrated by capture on streptavidin-coated magnetic
      beads, after coupling a biotinylated haloalkane ligand, or after on-phage
      extension of a DNA oligonucleotide primer with a biotinylated nucleotide by phi29
      DNA polymerase. We also achieved co-display of HaloTag and phi29 DNA polymerase,
      thereby opening perspectives for the molecular evolution of this enzyme (and
      others) towards new substrate specificities. 

PMID- 25772619
TI  - YY1 positively regulates human UBIAD1 expression.
AB  - Vitamin K is involved in bone formation and blood coagulation. Natural vitamin K
      compounds are composed of the plant form phylloquinone (vitamin K1) and a series
      of bacterial menaquionones (MK-n; vitamin K2). Menadione (vitamin K3) is an
      artificial vitamin K compound. MK-4 contains 4-isoprenyl as a side group in the 2
      methyl-1,4-naphthoquinone common structure and has various bioactivities. UbiA
      prenyltransferase domain containing 1 (UBIAD1 or TERE1) is the menaquinone-4
      biosynthetic enzyme. UBIAD1 transcript expression significantly decreases in
      patients with prostate carcinoma and overexpressing UBIAD1 inhibits proliferation
      of a tumour cell line. UBIAD1 mRNA expression is ubiquitous in mouse tissues, and
      higher UBIAD1 mRNA expression levels are detected in the brain, heart, kidneys
      and pancreas. Several functions of UBIAD1 have been reported; however, regulation
      of the human UBIAD1 gene has not been elucidated. Here we report cloning and
      characterisation of the human UBIAD1 promoter. A 5' rapid amplification of cDNA
      ends analysis revealed that the main transcriptional start site was 306
      nucleotides upstream of the translation initiation codon. Deletion and mutation
      analyses revealed the functional importance of the YY1 consensus motif.
      Electrophoretic gel mobility shift and chromatin immunoprecipitation assays
      demonstrated that YY1 binds the UBIAD1 promoter in vitro and in vivo. In
      addition, YY1 small interfering RNA decreased endogenous UBIAD1 mRNA expression
      and UBIAD1 conversion activity. These results suggest that YY1 up-regulates
      UBIAD1 expression and UBIAD1 conversion activity through the UBIAD1 promoter.

PMID- 25772620
TI  - Amino acid sequence surrounding the chondroitin sulfate attachment site of
      thrombomodulin regulates chondroitin polymerization.
AB  - Thrombomodulin (TM) is a cell-surface glycoprotein and a critical mediator of
      endothelial anticoagulant function. TM exists as both a chondroitin sulfate (CS)
      proteoglycan (PG) form and a non-PG form lacking a CS chain (alpha-TM);
      therefore, TM can be described as a part-time PG. Previously, we reported that
      alpha-TM bears an immature, truncated linkage tetrasaccharide structure
      (GlcAbeta1-3Galbeta1-3Galbeta1-4Xyl). However, the biosynthetic mechanism to
      generate part-time PGs remains unclear. In this study, we used several mutants to
      demonstrate that the amino acid sequence surrounding the CS attachment site
      influences the efficiency of chondroitin polymerization. In particular, the
      presence of acidic residues surrounding the CS attachment site was indispensable
      for the elongation of CS. In addition, mutants defective in CS elongation did not
      exhibit anti-coagulant activity, as in the case with alpha-TM. Together, these
      data support a model for CS chain assembly in which specific core protein
      determinants are recognized by a key biosynthetic enzyme involved in chondroitin
      polymerization. 

PMID- 25772622
TI  - C. elegans as a tool for in vivo nanoparticle assessment.
AB  - Characterization of the in vivo behavior of nanomaterials aims to optimize their
      design, to determine their biological effects, and to validate their application.
      The characteristics of the model organism Caenorhabditis elegans (C. elegans)
      advocate this 1mm long nematode as an ideal living system for the primary
      screening of engineered nanoparticles in a standard synthetic laboratory. This
      review describes some practicalities and advantages of working with C. elegans
      that will be of interest for chemists and materials scientists who would like to
      enter the "worm" community, anticipates some drawbacks, and offers relevant
      examples of nanoparticle assessment by using C. elegans. 

PMID- 25772621
TI  - Serious infections among adult Medicaid beneficiaries with systemic lupus
      erythematosus and lupus nephritis.
AB  - OBJECTIVE: To examine the epidemiology of serious infections, a significant cause
      of morbidity and mortality in systemic lupus erythematosus (SLE), in a nationwide
      cohort of SLE and lupus nephritis (LN) patients. METHODS: Using the Medicaid
      Analytic eXtract database for the years 2000-2006, we identified patients ages 18
      64 years who had SLE and the subset who had LN. We ascertained cases of serious
      hospitalized infections using validated algorithms, and we determined 30-day
      mortality rates. Poisson regression was used to calculate infection incidence
      rates and multivariable Cox proportional hazards models were used to calculate
      hazard ratios (HRs) for the first infection, adjusted for sociodemographic
      variables, medication use, and an SLE-specific risk adjustment index. RESULTS: We
      identified 33,565 patients with SLE, 7,113 of whom had LN. There were 9,078
      serious infections in 5,078 SLE patients and 3,494 infections in 1,825 LN
      patients. The infection incidence rate per 100 person-years was 10.8 in the SLE
      cohort and 23.9 in the LN subcohort. In adjusted models for the SLE cohort, we
      observed increased risks of infection in men as compared to women (HR 1.33 [95%
      confidence interval (95% CI) 1.20-1.47]), in blacks as compared to whites (HR
      1.14 [95% CI 1.06-1.21]), and in users of glucocorticoids (HR 1.51 [95% CI 1.43
      1.61]) and immunosuppressive drugs (HR 1.11 [95% CI 1.03-1.20]) as compared to
      never users. Hydroxychloroquine users had a reduced risk of infection as compared
      to never users (HR 0.73 [95% CI 0.68-0.77]). The 30-day mortality rate per 1,000
      person-years among those hospitalized with infections was 21.4 in the SLE cohort
      and 38.6 in the LN subcohort. CONCLUSION: In this diverse, nationwide cohort of
      SLE patients, we observed a substantial burden of serious infections with many
      subsequent deaths, particularly among those with LN.

PMID- 25772623
TI  - A numerical investigation on the drainage of a surfactant-modified water droplet
      in paraffin oil.
AB  - A volume of fluid approach is used in numerical simulations of the settling
      motion of a surfactant modified water droplet in a continuous paraffin oil phase.
      The droplet is millimeter-sized and confined in a square two dimensional domain.
      The surfactant interfacial and bulk concentration-equations are solved together
      with the incompressible Navier-Stokes equation. The role of boundary walls in the
      overall settling dynamics is described. As the droplet moves downwards the
      interfacial shear creates non-homogeneous interfacial surfactant concentrations
      and Marangoni driven phenomena come into play. A decrease of the drainage
      velocity is then evidenced indicating that buoyancy forces are counter balanced
      by Marangoni induced lift-forces. The lateral migration of the droplet due to
      boundary wall proximity is discussed. It is shown to increase with wall proximity
      and to decrease when increasing the interfacial concentration. Finally, a
      simplified model is used to investigate the evolution of the bulk concentration
      assuming the surfactant is insoluble in paraffin oil and poorly soluble in water.

PMID- 25772624
TI  - Sleepless latency of human cytomegalovirus.
AB  - As with all human herpesviruses, human cytomegalovirus (HCMV) persists for the
      lifetime of the host by establishing a latent infection, which is broken by
      periodic reactivation events. One site of HCMV latency is in the progenitor cells
      of the myeloid lineage such as CD34+ cells and their CD14+ derivatives. The
      development of experimental techniques to isolate and culture these primary cells
      in vitro is enabling detailed analysis of the events that occur during virus
      latency and reactivation. Ex vivo differentiation of latently infected primary
      myeloid cells to dendritic cells and macrophages results in the reactivation of
      latent virus and provides model systems in which to analyse the viral and
      cellular functions involved in latent carriage and reactivation. Such analyses
      have shown that, in contrast to primary lytic infection or reactivation which is
      characterised by a regulated cascade of expression of all viral genes, latent
      infection is associated with a much more restricted viral transcription programme
      with expression of only a small number of viral genes. Additionally, concomitant
      changes in the expression of cellular miRNAs and cellular proteins occur, and
      this includes changes in the expression of a number of secreted cellular proteins
      and intracellular anti-apoptotic proteins, which all have profound effects on the
      latently infected cells. In this review, we concentrate on the effects of one of
      the latency-associated viral proteins, LAcmvIL-10, and describe how it causes a
      decrease in the cellular miRNA, hsa-miR-92a, and a concomitant upregulation of
      the GATA2 myeloid transcription factor, which, in turn, drives the expression of
      cellular IL-10. Taken together, we argue that HCMV latency, rather than a period
      of viral quiescence, is associated with the virally driven manipulation of host
      cell functions, perhaps every bit as complex as lytic infection. A full
      understanding of these changes in cellular and viral gene expression during
      latent infection could have far-reaching implications for therapeutic
      intervention. 

PMID- 25772625
TI  - Physical Therapy or Advanced Imaging as First Management Strategy Following a New
      Consultation for Low Back Pain in Primary Care: Associations with Future Health
      Care Utilization and Charges.
AB  - OBJECTIVE: Compare health care utilization and charges for low-back-pain (LBP)
      patients receiving advanced imaging or physical therapy as a first management
      strategy following a new primary care consultation. DATA SOURCE: Electronic
      medical record (EMR) and insurance claims data. STUDY DESIGN: Retrospective
      analysis of propensity-matched groups. DATA COLLECTION/EXTRACTION: Claims and EMR
      data were used. Utilization and LBP-related charges over a 1-year period were
      extracted from claims data. PRINCIPAL FINDINGS: In the propensity-matched sample
      (n = 406), advanced imaging recipients had higher odds of all utilization
      outcomes. Charges were higher with advanced imaging by an average $4,793 (95
      percent CI: $3,676, $5,910). CONCLUSIONS: For patients with LBP whom newly
      consulted primary care referred for additional management, advanced imaging as a
      first management was associated with higher health care utilization and charges
      than physical therapy.

PMID- 25772626
TI  - National cohort study of opioid analgesic dose and risk of future
      hospitalization.
AB  - BACKGROUND: High daily and total doses of opioid analgesics (OAs) increase the
      risk for drug overdose and may be risks for all-cause hospitalization. OBJECTIVE:
      To examine the association of OA dose measures with future all-cause
      hospitalization. DESIGN/PATIENTS: Cohort study of 87,688 national health
      maintenance organization enrollees aged 45 to 64 years with noncancer pain who
      filled >=2 OA prescriptions from January 2009 to July 2012. METHODS: Outcomes
      were all-cause hospitalization and hospital days in 6-month intervals after the
      first OA was filled. In generalized linear mixed models, we examined interactions
      of 5 daily OA dose categories and 5 total dose categories in each 6-month
      interval adjusted for demographics, clinical conditions, psychotropic drugs, and
      current hospitalization. For high total OA doses, percentage of days covered by
      OA prescriptions in 6 months was examined. RESULTS: Over 3 years, an average of
      12% of subjects were hospitalized yearly for a mean 6.5 (standard deviation =
      8.5) days. Compared with no OAs, adjusted odds of future hospitalization for high
      total opioid dose (>1830 mg) were 35% to 44% greater depending on daily dose
      category (all P < 0.05), but total OA dose <=1830 mg had weak or no association
      with future hospitalization regardless of daily OA dose. For high total OA doses,
      odds of hospitalization were 41% to 51% greater for categories of percentage of
      time on OAs above >50% (>3 months) versus no OAs (all P < 0.05). Similar effects
      were observed for hospital days. CONCLUSIONS: Higher total OA doses for >3 months
      within a 6-month period significantly increased the risk for all-cause
      hospitalization and longer inpatient stays in the next 6 months.

PMID- 25772627
TI  - Family Nurture Intervention in preterm infants alters frontal cortical functional
      connectivity assessed by EEG coherence.
AB  - AIM: To assess the impact of Family Nurture Intervention (FNI) on cortical
      function in preterm infants at term age. METHODS: Family Nurture Intervention is
      a NICU-based intervention designed to establish emotional connection between
      mothers and preterm infants. Infants born at 26-34 weeks postmenstrual age (PMA)
      were divided into two groups, standard care (SC, N = 49) and FNI (FNI, N = 56).
      Infants had EEG recordings of ~one hour duration with 124 lead nets between 37
      and 44 weeks PMA. Coherence was measured between all pairs of electrodes in ten
      frequency bands. Data were summarised both within and between 12 regions during
      two sleep states (active, quiet). RESULTS: Coherence levels were negatively
      correlated with PMA age in both groups. As compared to SC infants, FNI infants
      showed significantly lower levels of EEG coherence (1-18 Hz) largely within and
      between frontal regions. CONCLUSION: Coherence in FNI infants was decreased in
      regions where we previously found robust increases in EEG power. As coherence
      decreases with age, results suggest that FNI may accelerate brain maturation
      particularly in frontal brain regions, which have been shown in research by
      others to be involved in regulation of attention, cognition and emotion
      regulation; domains deficient in preterm infants.

PMID- 25772628
TI  - The predicted ensemble of low-energy conformations of human somatostatin receptor
      subtype 5 and the binding of antagonists.
AB  - Human somatostatin receptor subtype 5 (hSSTR5) regulates cell proliferation and
      hormone secretion. However, the identification of effective therapeutic small
      molecule ligands is impeded because experimental structures are not available for
      any SSTR subtypes. Here, we predict the ensemble of low-energy 3D structures of
      hSSTR5 using a modified GPCR Ensemble of Structures in Membrane BiLayer
      Environment (GEnSeMBLE) complete sampling computational method. We find that this
      conformational ensemble displays most interhelical interactions conserved in
      class A G protein-coupled receptors (GPCRs) plus seven additional interactions
      (e.g., Y2.43-D3.49, T3.38-S4.53, K5.64-Y3.51) likely conserved among SSTRs. We
      then predicted the binding sites for a series of five known antagonists, leading
      to predicted binding energies consistent with experimental results reported in
      the literature. Molecular dynamics (MD) simulation of 50 ns in explicit water and
      lipid retained the predicted ligand-bound structure and formed new interaction
      patterns (e.g. R3.50-T6.34) consistent with the inactive MU-opioid receptor X-ray
      structure. We suggest more than six mutations for experimental validation of our
      prediction. The final predicted receptor conformations and antagonist binding
      sites provide valuable insights for designing new small-molecule drugs targeting
      SSTRs.

PMID- 25772629
TI  - Fasting heat production and metabolic BW in group-housed broilers.
AB  - Fasting heat production (FHP) is used for characterizing the basal metabolic rate
      of animals and the corresponding maintenance energy requirements and in the
      calculation of net energy value of feeds. In broilers, the most recent FHP
      estimates were obtained in the 1980s in slow-growing and fatter birds than
      nowadays. The FHP values (n=73; six experiments) measured in 3 to 6-week-old
      modern lines of broilers weighing 0.6 to 2.8 kg and growing at 80 to 100 g/day
      were used to update these literature values. Each measurement was obtained in a
      group of fasting broilers (5 to 14 birds) kept in a respiration chamber for at
      least 24 h. The FHP estimate corresponds to the asymptotic heat production
      corrected for zero physical activity obtained by modeling the decrease in heat
      production during the fasting day. The compilation of these data indicates that
      FHP was linearly related to the BW(0.70) (in kg), which can be considered as the
      metabolic BW of modern broilers. The 0.70 exponent differs from the conventional
      value of 0.75 used for mature animals. The FHP per kg of BW(0.70) ranged between
      410 and 460 kJ/day according to the experiment (P<0.01). An experiment conducted
      with a shorter duration of fasting (16 h) indicated that FHP values are higher
      than those obtained over at least 24 h of fasting. Our values are similar to
      those obtained previously on fatter and slow-growing birds, even though the
      comparison is difficult since measurement conditions and methodologies have
      changed during the last 30 years. The FHP values obtained in our trials represent
      a basis for energy nutrition of modern broilers.

PMID- 25772631
TI  - Erythropoietin receptor mutation--a rush of blood to the head?

PMID- 25772630
TI  - Trends in quality of non-Hodgkin's lymphoma care: is it getting better?
AB  - This study outlines trends in quality of delivered non-Hodgkin's lymphoma (NHL)
      care in the Netherlands between 2007 and 2011 and to what extend this was
      influenced by the national Visible Care program, which aimed at increasing
      transparency by providing insight into the quality of healthcare. We analyzed
      data collected from medical records in two observational studies, combined into
      20 validated quality indicators (QIs) of which 6 were included in the national
      program. A random sample of 771 patients, diagnosed with NHL in 26 Dutch
      hospitals, was examined. Multilevel regression analyses were used to assess
      differences in quality of NHL care and to provide insight into the effect of the
      national program. We reported improved adherence to only 3 out of 6 QIs involved
      in the national program and none of the other 14 validated QIs. Improvement was
      shown for performance of all recommended staging techniques (from 26  to  43 %),
      assessment of International Prognostic Index (from 21  to  43 %), and
      multidisciplinary discussion of patients (from 23  to  41 %). We found limited
      improvement in quality of NHL care between 2007 and 2011; improvement potential
      (<80 % adherence) was still present for 13 QIs. The national program seems to
      have a small positive effect, but has not influenced all 20 indicators which
      represent the most important, measurable parts in quality of NHL care. These
      results illustrate the need for tailored implementation and quality improvement
      initiatives. 

PMID- 25772632
TI  - The occurrence and pathogenicity of Serratospiculum tendo (Nematoda:
      Diplotriaenoidea) in birds of prey from southern Italy.
AB  - The air sacs of free-ranging birds of prey (n= 652) from southern Italy,
      including 11 species of Accipitriformes and six of Falconiforms, were examined
      for infections with Serratospiculum tendo (Nematoda: Diplotriaenoidea). Of the 17
      species of birds examined, 25 of 31 (80.6%) peregrine falcons (Falco peregrinus)
      from Calabria Region and a single northern goshawk (Accipiter gentilis) from
      Campania Region were infected with S. tendo, suggesting a strong host specificity
      for the peregrine falcon. The northern goshawk and 18 of 25 infected peregrine
      falcons showed cachexia and all infected birds had bone fractures. At gross
      examination, air sacculitis and pneumonia were the most common lesions in
      infected birds. Microscopically, the air-sac walls showed thickening of the
      smooth muscle cells, resulting in a papillary appearance, along with hyperplasia
      of the mesothelium and epithelium, and foci of plasma cell infiltration and
      macrophages associated with several embryonated eggs and adult parasites.
      Extensive areas of inflammation were found in the lungs, characterized by
      lymphocytes, macrophages and fibroblasts surrounding embryonated eggs. The
      northern goshawk also had detachment of the dextral lung with several necrotic
      foci. In this case, the death of the bird was directly attributed to S. tendo
      infection. Lesions and pathological changes observed here suggest that S. tendo
      can cause disease. 

PMID- 25772633
TI  - A Novel Electrocardiographic T-Wave Measurement (Tp-Te Interval) as a Predictor
      of Heart Abnormalities in Hypertension: A New Opportunity for First-Line
      Electrocardiographic Evaluation.
AB  - The aim of the study was to evaluate the role of conventional and new markers of
      early cardiac organ damage (OD) on 12-lead electrocardiography (ECG) in 25
      outpatients with newly diagnosed untreated essential hypertension compared with
      15 normotensive, otherwise healthy individuals. Each participant underwent ECG,
      echocardiographic, and blood pressure (BP) measurements. Conventional and new ECG
      indexes for cardiac OD (Tp-Te interval, ventricular activation time, and P-wave
      analysis) were also measured. Clinic and 24-hour ambulatory BP levels as well as
      left ventricular mass indexes were significantly higher in hypertensive than in
      normotensive patients. No significant differences were found between the two
      groups for ECG and echocardiographic markers of OD. Only Tp-Te interval was
      higher in hypertensive than in normotensive individuals (3.06 mm vs 2.24 mm;
      P<.0001), even after adjustment for anthropometric and clinical parameters.
      Preliminary results of this study demonstrated prolonged Tp-Te interval in newly
      diagnosed, untreated hypertensive outpatients compared with normotensive
      individuals.

PMID- 25772637
TI  - Puzzles in practice. Bi-thalamic infarction.

PMID- 25772634
TI  - Effects of red wine on postprandial stress: potential implication in non
      alcoholic fatty liver disease development.
AB  - INTRODUCTION: Red wine consumption is considered to be protective against
      oxidative stress. Diet strongly influences non-alcoholic fatty liver disease,
      which is associated with oxidative stress and is considered the hepatic
      manifestation of the metabolic syndrome. METHODS: We reviewed the available
      evidence that investigated the effects of red wine on the postprandial-induced
      metabolic and oxidative stress in humans. RESULTS: After red wine consumption
      with meal, despite the improvement in non-enzymatic antioxidant capacity and
      lipoperoxidation markers, the influence of confounding factors such as uric acid
      should be taken into account. Both uric acid and triglycerides increases, induced
      by ethanol, could cause liver damage. On the other hand, further researches are
      required in order to understand the meaning of the induction of antioxidant
      enzymes by red wine and red wine polyphenols in the context of non-alcoholic
      fatty liver disease. CONCLUSION: In conclusion, inconsistent and contrasting
      findings exist regarding the potential benefits of red wine consumption against
      postprandial stress.

PMID- 25772638
TI  - Are medical comorbid conditions of bipolar disorder due to immune dysfunction?
AB  - OBJECTIVE: Epidemiological data have shown a clear association between bipolar
      disorder (BD) and medical comorbidities. The aim of this article was to assess
      the evidence of immune dysfunction as a key mediator of this observed
      association. METHOD: For this narrative clinical overview, the MEDLINE/PubMed,
      EMBASE, Google Scholar, and ClinicalTrials.gov databases were searched for
      relevant articles. RESULTS: Bipolar disorder has been shown to have an increased
      prevalence in patients with autoimmune disorders, cardiovascular disease, and
      metabolic dysfunction. Further, an elevation in proinflammatory cytokines in BD
      has been repeatedly demonstrated. Several mechanisms have been proposed to
      explain the effect of immune dysfunction on mood and cognition. Anti-inflammatory
      agents including TNF-alpha inhibitors, non-steroidal anti-inflammatory drugs
      (NSAIDs), minocycline and omega-3 polyunsaturated fatty acids (O3PUFA) are being
      investigated for their use as novel treatment of BD in patients with immune
      dysfunction. CONCLUSION: Immune dysfunction appears to be an important mediator
      of the association observed between BD and medical comorbidities. It therefore
      serves as a potential novel target for treatment of BD. Further, the observed
      bidirectional interaction merits screening for psychiatric disorders in patients
      with immune dysfunction and vice versa to allow for early detection and treatment
      of this at risk population.

PMID- 25772635
TI  - Association between yogurt consumption, dietary patterns, and cardio-metabolic
      risk factors.
AB  - PURPOSE: To examine whether yogurt consumption is associated with a healthier
      dietary pattern and with a better cardio-metabolic risk profile among healthy
      individuals classified on the basis of their body mass index (BMI). METHODS: A 91
      item food frequency questionnaire, including data on yogurt consumption, was
      administered to 664 subjects from the INFOGENE study. After principal component
      analysis, two factors were retained, thus classified as the Prudent and Western
      dietary patterns. RESULTS: Yogurt was a significant contributor to the Prudent
      dietary pattern. Moreover, yogurt consumption was associated with lower body
      weight, waist-to-hip ratio, and waist circumference and tended to be associated
      with a lower BMI. Consumers had lower levels of fasting total cholesterol and
      insulin. Consumers of yogurt had a positive Prudent dietary pattern mean score,
      while the opposite trend was observed in non-consumers of yogurt.
      Overweight/obese individuals who were consumers of yogurts exhibited a more
      favorable cardio-metabolic profile characterized by lower plasma triglyceride and
      insulin levels than non-consumers within the same range of BMI. There was no
      difference in total yogurt consumption between normal-weight individuals and
      overweight/obese individuals. However, normal-weight subjects had more daily
      servings of high-fat yogurt and less daily servings of fat-free yogurt compared
      to overweight/obese individuals. CONCLUSIONS: Being a significant contributor to
      the Prudent dietary pattern, yogurt consumption may be associated with healthy
      eating. Also, yogurt consumption may be associated with lower anthropometric
      indicators and a more beneficial cardio-metabolic risk profile in
      overweight/obese individuals.

PMID- 25772639
TI  - Human intestinal gas measurement systems: in vitro fermentation and gas capsules.
AB  - The biological and clinical significance of the human gut microbiome is currently
      attracting worldwide attention. While rRNA and DNA technologies led to a quantum
      leap in our understanding of the numbers and types of gut microorganisms, much
      less is known about these microorganisms' activity in situ and in real time.
      Accurately measuring their byproducts, including intestinal gases, may offer
      unique biomarkers for specific gut microbiota, accelerating our understanding of
      the relationships among intestinal gases, the metabolic activity of the gut
      microbiome, and human health states. Here we present two novel techniques, namely
      in vitro fermentation and gas capsule systems, for measuring and assessing
      selected gas species. We discuss new developments with these technologies and the
      methods of their implementation and provide an overall review of their operation.

PMID- 25772640
TI  - Transitioning safely from intravenous to subcutaneous insulin.
AB  - The transition from intravenous (IV) to subcutaneous (SQ) insulin in the
      hospitalized patient with diabetes or hyperglycemia is a key step in patient
      care. This review article suggests a stepwise approach to the transition in order
      to promote safety and euglycemia. Important components of the transition include
      evaluating the patient and clinical situation for appropriateness, recognizing
      factors that influence a safe transition, calculation of proper SQ insulin doses,
      and deciding the appropriate type of SQ insulin. This article addresses other
      clinical situations including the management of patients previously on insulin
      pumps and recommendations for patients requiring glucocorticoids and enteral tube
      feedings. The use of institutional and computerized protocols is discussed.
      Further research is needed regarding the transition management of subgroups of
      patients such as those with type 1 diabetes and end-stage renal disease. 

PMID- 25772641
TI  - Non-ICU hospital care of diabetes mellitus in the elderly population.
AB  - The concept of lower is better when considering the goal for glycemic control in
      patients with diabetes mellitus has recently been challenged due to recent
      studies, such as ACCORD, ADVANCE, and VADT, which have observed increased
      morbidity and mortality from intensive control, especially in older adults, and
      in those with long duration of diabetes disease and chronic complications.
      Although evidence in younger patients suggest that blood glucose levels should
      not be above 180 mg/dl (10.0 mmol/l), there are many unanswered questions and
      controversies regarding the benefits and risks, methods to achieve and maintain
      these levels while avoiding hypoglycemia (<70 mg% (3.9 mmol/l)) in the older
      population. Since the population is aging with a greater life expectancy, it is
      crucial that these questions be answered. Although several studies of inpatient
      non-ICU diabetes management have been published, few include older patients. This
      review will examine available recommendations and explore those controversies
      regarding non-ICU hospital management in this vulnerable patient population.
      Additional conditions that impact upon achieving glycemic control will also be
      discussed. Finally, the older individual has many special needs which may be more
      important to consider than in young or middle-aged individuals, when
      transitioning care from in-hospital to home in a patient-centered approach, as
      recommended by the American Diabetes Association (ADA) and European Society for
      the Study of Diabetes (EASD).

PMID- 25772642
TI  - Is fenofibrate a reasonable treatment for diabetic microvascular disease?
AB  - Type 2 diabetes is a pandemic disease, and its prevalence is increasing mainly
      due to an increase in obesity and life expectancy. Diabetic complications and
      their comorbidities constitute the most important economic cost of the disease
      and represent a significant economic burden for the healthcare systems of
      developed countries. Despite improving standards of care, people with diabetes
      remain at risk of the development and progression of microvascular diabetic
      complications. Therefore, the identification of novel therapeutic approaches is
      necessary. The aim of this article is to provide an overview of the clinical
      benefits of fenofibrate on microvascular diabetic complications, with special
      emphasis on diabetic retinopathy. In addition, the potential mechanisms of action
      will be briefly discussed. 

PMID- 25772643
TI  - Management of glycemia in diabetic patients with stage IV and V chronic kidney
      disease.
AB  - Diabetic kidney disease is a leading cause of end-stage kidney disease worldwide.
      Data suggest that prevention of progression to end-stage may lie in excellent
      blood glucose control; however, as kidney disease progresses, the risk of
      hypoglycemia increases, due to unpredictable insulin kinetics and altered
      pharmacokinetics of hypoglycemic agents. In addition, whole classes of
      hypoglycemic agents become contraindicated and regimens must be adjusted for
      declining kidney function. There is no consensus regarding the best therapy for
      the patient with advanced chronic kidney disease. In the best of circumstances,
      the care of these patients will involve intensive monitoring, with the input of a
      team of health care providers creating a coordinated care plan, including dietary
      advice and a drug regimen tailored to the specific issues faced by the individual
      patient. An open dialogue is necessary at all times, as patients may become
      frustrated and attempt self-treatment using over the counter alternatives. 

PMID- 25772644
TI  - Colistin treatment in carbapenem-resistant Acinetobacter baumannii pneumonia
      patients: Incidence of nephrotoxicity and outcomes.
AB  - Colistimethate sodium (CMS) is increasingly used to treat multidrug-resistant
      Gram-negative bacilli infections. However, the incidence of CMS-associated
      nephrotoxicity has not been evaluated in patients with carbapenem-resistant
      Acinetobacter baumannii (CRAB) pneumonia. This retrospective study included 120
      patients with CRAB pneumonia treated with intravenous CMS for >=72 h. The
      objective of the study was to determine risk factors for CMS-induced
      nephrotoxicity and 30-day mortality in patients with CRAB pneumonia. Of the 120
      patients with CRAB pneumonia, 61 (51%) developed nephrotoxicity. Multivariate
      analysis showed that dose per ideal body weight (IBW) [odds ratio (OR)=1.28, 95%
      confidence interval (CI) 1.01-1.62; P=0.04], Charlson co-morbidity index
      (OR=1.31, 95% CI 1.06-1.60; P=0.01) and septic shock (OR=3.16, 95% CI 1.32-7.60;
      P=0.01) were associated with CMS-associated nephrotoxicity. Thirty-day mortality
      was 33% (39/120). Multivariate analysis showed that higher daily doses of CMS per
      IBW [hazard ratio (HR)=0.81, 95% CI 0.67-0.98; P=0.03] and longer duration of CMS
      therapy (HR=0.86, 95% CI 0.79-0.95; P=0.002) were associated with increased
      survival. Septic shock (HR=3.91, 95% CI 1.95-7.83; P<0.001) and corticosteroid
      use (HR=3.49, 95% CI 1.67-7.28; P=0.001) were associated with decreased survival
      in patients with CRAB pneumonia. Higher daily doses of CMS per IBW, Charlson
      comorbidity index and septic shock were significant risk factors for CMS
      associated nephrotoxicity. However, CMS-associated nephrotoxicity does not appear
      to have an impact on mortality.

PMID- 25772645
TI  - Meeting current musculoskeletal health demand through deeper insights into tissue
      homeostasis and regeneration.
AB  - The burden of chronic musculoskeletal disorders is challenging and prompts
      therapeutic advancements. The notion that chronic conditions such as
      osteoarthritis and tendinopathy are linked to deficient healing by failure of one
      or several of the cellular/molecular processes involved is gaining ground.
      Alterations underpinning disruption of healing mechanisms that contribute to the
      development of chronic musculoskeletal pathologies include unresolved
      inflammation, abnormal angiogenic status, alterations in paracrine communication,
      decline in stem cell functioning and inability to maintain homeostasis in the
      extracellular matrix compartment. The complexity of failed healing may be
      challenged with interventions that target multiple biological processes such as
      cell therapies and/or platelet-rich plasma. 

PMID- 25772646
TI  - Perspectives on thyroid hormone action in adult neurogenesis.
AB  - Thyroid hormone exhibits profound effects on neural progenitor turnover,
      survival, maturation, and differentiation during perinatal development. Studies
      over the past decade have revealed that thyroid hormone continues to retain an
      important influence on progenitors within the neurogenic niches of the adult
      mammalian brain. The focus of the current review is to critically examine and
      summarize the current state of understanding of the role of thyroid hormone in
      regulating adult neurogenesis within the major neurogenic niches of the
      subgranular zone in the hippocampus and the subventricular zone lining the
      lateral ventricles. We review in depth the studies that highlight a role for
      thyroid hormone, in particular the TRalpha1 receptor isoform, in regulating
      progenitor survival and commitment to a neuronal fate. We also discuss putative
      models for the mechanism of action of thyroid hormone/TRalpha1 on specific stages
      of subgranular zone and subventricular zone progenitor development, and highlight
      potential thyroid hormone responsive target genes that may contribute to the
      neurogenic effects of thyroid hormone. The effects of thyroid hormone on adult
      neurogenesis are discussed in the context of a potential role of these effects in
      the cognitive- and mood-related consequences of thyroid hormone dysfunction.
      Finally, we detail hitherto unexplored aspects of the effects of thyroid hormone
      on adult neurogenesis that provide impetus for future studies to gain a deeper
      mechanistic insight into the neurogenic effects of thyroid hormone. Thyroid
      hormone regulation of adult neurogenesis in the mammalian brain exhibits both
      unique and overlapping effects within distinct neurogenic niches. Thyroid hormone
      regulates hippocampal subgranular zone (SGZ) progenitor survival and neuronal
      cell fate acquisition and influences subventricular zone (SVZ) progenitor cell
      turnover, cell cycle exit, and neuronal cell fate acquisition. In this review, we
      summarize, critically discuss and highlight open questions in regard to thyroid
      hormone regulation of adult neurogenesis. 

PMID- 25772648
TI  - Dynamic interface charge governing the current-voltage hysteresis in perovskite
      solar cells.
AB  - The accumulation of mobile ions causes space charge at interfaces in perovskite
      solar cells. There is a slow dynamic process of ion redistribution when the bias
      is changed. The interface charge affects band bending and thus the photocurrent
      of the solar cells. Consequently the dynamic process of the interface charge
      governs the current-voltage hysteresis. Very low interface charge density leads
      to hysteresis-free devices. 

PMID- 25772647
TI  - Is the presence of a non-cleaved embryo on day 3 associated with poorer quality
      of the remaining embryos in the cohort?
AB  - PURPOSE: Morphological evaluation is currently considered the single most
      important predictive measure for assessing embryo quality. The aim of this study
      was to investigate whether cycles with at least one non-cleaved embryo (i.e., a 1
      cell embryo on day 3) have different outcomes compared with cycles in which all
      embryos had cleaved by day 3. METHODS: All autologous IVF/ICSI cycles with a
      fresh day 3 transfer and without using a gestational carrier performed at our
      center between 1/1/2010 and 12/31/2011 were analyzed retrospectively. Those
      cycles with at least one non-cleaved embryo on day 3 were compared with all other
      autologous cycles that had 100% cleaved embryos performed during the study
      period. RESULTS: Eight hundred and forty two cycles were included. Of them, 144
      cycles comprised the non-cleaved group, and 698 cycles comprised the cleaved
      group. Cycles in the non-cleaved group had more oocytes retrieved (15.4 +/- 7.1
      vs. 12.5 +/- 7.1, p < 0.001), more zygotes obtained (10.0 +/- 5.3 vs. 7.9 +/-
      5.2, p = <0.001), but the embryos exhibited lower cleavage rates and higher rates
      of fragmentation and asymmetry compared with controls (p < 0.001). However,
      spontaneous abortion rates, ectopic pregnancies rates as well as delivery rates
      were similar between the two groups. CONCLUSIONS: Our results show that the
      presence of a non-cleaved embryo on day 3 is associated with a more exuberant
      response to controlled ovarian stimulation as reflected by more oocytes
      retrieved. Despite the significant decrease in quality of the whole cohort in the
      non-cleaved group, implantation, delivery rates and number of embryos frozen were
      not adversely affected by the presence of a non-cleaved embryo.

PMID- 25772649
TI  - Impact of asthma medication and familial factors on the association between
      childhood asthma and attention-deficit/hyperactivity disorder: a combined twin-
      and register-based study: Epidemiology of Allergic Disease.
AB  - BACKGROUND: Asthma and attention-deficit/hyperactivity disorder (ADHD) are
      prevalent in childhood and may cause functional impairment and stress in
      families. Previous research supports an association between asthma and ADHD in
      children, but several aspects of this relationship are unclear. OBJECTIVE: Our
      aim was to study whether the association between asthma and ADHD is restricted to
      either the inattentive or the hyperactive/impulsive symptoms of ADHD, to explore
      the impact of asthma severity and asthma medication and the contribution of
      shared genetic and environmental risk factors on the asthma-ADHD relationship.
      METHODS: Data on asthma, ADHD, zygosity and possible confounders were collected
      from parental questionnaires at 9 or 12 years on 20 072 twins through the Swedish
      Twin Register, linked to the Swedish Medical Birth Register, the National Patient
      Register and the Prescribed Drug Register. The association between asthma and
      ADHD, the impact of asthma severity and medication, was assessed by generalized
      estimating equations. Cross-twin-cross-trait correlations (CTCT) were estimated
      to explore the relative importance of genes and environment for the association.
      RESULTS: Asthmatic children had a higher risk of also having ADHD [odds ratio
      (OR) 1.53, 95% confidence interval (CI): 1.16-2.02]. The association was not
      restricted to either of the two dimensions of ADHD. The magnitude of the
      association increased with asthma severity (OR 2.84, 95% CI: 1.86-4.35) for >= 4
      asthma attacks in the last 12 months and was not affected by asthma treatment.
      The CTCTs possibly indicate that the genetic component in overlap of the
      disorders is weak. CONCLUSIONS AND CLINICAL RELEVANCE: Childhood asthma,
      especially severe asthma, is associated with ADHD. Asthma medication seems not to
      increase the risk of ADHD. Clinicians should be aware of the potential of ADHD in
      asthma. Optimal asthma care needs to be integrated with effective evaluation and
      treatment of ADHD in children with co-existing disorders.

PMID- 25772650
TI  - Systemic oxidative profile after tumor removal and the tumor microenvironment in
      melanoma patients.
AB  - This study highlights the systemic oxidative changes in patients submitted to
      primary cutaneous melanoma removal. Cutaneous melanoma is highly aggressive and
      its incidence is increasing worldwide. We evaluated systemic oxidative stress
      (OS) and 3-nitrotyrosine (3-NT) expression in melanoma tissue in relation to the
      Breslow thickness in patients under surveillance. Forty-three patients with
      cutaneous melanoma and 50 healthy volunteers were recruited. Patients were
      divided into two groups according to the tumor's Breslow thickness: T1/T2 (<2 mm)
      and T3/T4 (>=2 mm). Systemic OS and inflammatory mediators were evaluated in
      plasma, and the 3-NT expression was analyzed via immunohistochemistry. Compared
      with the controls, the patients had lower blood levels of reduced glutathione,
      higher malondialdehyde and thiol levels, and a higher total radical-trapping
      antioxidant parameter to uric acid ratio. The C-reactive protein and gamma
      glutamyl transpeptidase were increased only in the T3/T4 group. High levels of 3
      NT were present only in T3/T4 patients. Our data suggested that a correlation
      exists between the Breslow thickness and a systemic pro-oxidant status, and that
      oxidative changes induced by the melanoma remain in the microenvironment post
      surgery, demonstrating a role for oxygen species in melanoma. 

PMID- 25772651
TI  - [New conduction disturbances and pacemaker indications after CoreValve(r)
      transcatheter aortic valve replacement. Incidence and follow up in a single
      center experience].
AB  - INTRODUCTION: Transcatheter aortic valve implantation (TAVI) is currently
      reserved for patients with symptomatic aortic stenosis and high surgical risk.
      One major limiting factor related to TAVI procedural complications is conduction
      abnormalities and the need for permanent pacemaker implantation. OBJECTIVES:
      Evaluate the incidence of new conduction disturbances and pacemaker indications
      in patients with TAVI CoreValve(r) prosthesis (Medtronic Inc. Minneapolis,
      Minnesota, United States). METHODS: We included 28 patients, mean age 80 years.
      ECG parameters were evaluated previous and after implantation. All patients were
      monitorized during TAVI. Follow up Holter monitoring was performed at one, 6 and
      12 months after the procedure and we also evaluated telemetry of implanted
      pacemaker. RESULTS: In previous ECG we found 7 patients had right bundle branch
      block and 7 patients had left bundle brunch block (LBBB). The post implant ECG
      showed 7 new LBBB: 3 during valvuloplasty and 4 on the end of it. Six patients
      required pacemaker implantation for permanent or paroxysmal complete AV block
      (CAVB). At one year follow up, 3 patients with LBBB during valvuloplasty had a
      normal ECG, one still had LBBB and one an asymptomatic CAVB found in Holter
      monitoring. CONCLUSIONS: Conduction abnormalities are frequent after CoreValve(r)
      aortic valve prosthesis implantation. The incidence of new LBBB was 25%. CAVB
      during or post TAVI require PM implantation. New LBBB may need a closer follow up
      because in a 3% of the cases it may progress to CAVB.

PMID- 25772652
TI  - Beyond Sexual Orientation: Integrating Gender/Sex and Diverse Sexualities via
      Sexual Configurations Theory.
AB  - Sexual orientation typically describes people's sexual attractions or desires
      based on their sex relative to that of a target. Despite its utility, it has been
      critiqued in part because it fails to account for non-biological gender-related
      factors, partnered sexualities unrelated to gender or sex, or potential
      divergences between love and lust. In this article, I propose Sexual
      Configurations Theory (SCT) as a testable, empirically grounded framework for
      understanding diverse partnered sexualities, separate from solitary sexualities.
      I focus on and provide models of two parameters of partnered sexuality-
      gender/sex and partner number. SCT also delineates individual gender/sex. I
      discuss a sexual diversity lens as a way to study the particularities and
      generalities of diverse sexualities without privileging either. I also discuss
      how sexual identities, orientations, and statuses that are typically seen as
      misaligned or aligned are more meaningfully conceptualized as branched or co
      incident. I map out some existing identities using SCT and detail its applied
      implications for health and counseling work. I highlight its importance for
      sexuality in terms of measurement and social neuroendocrinology, and the ways it
      may be useful for self-knowledge and feminist and queer empowerment and alliance
      building. I also make a case that SCT changes existing understandings and
      conceptualizations of sexuality in constructive and generative ways informed by
      both biology and culture, and that it is a potential starting point for sexual
      diversity studies and research.

PMID- 25772653
TI  - Call for Commentaries on van Anders (2015).

PMID- 25772654
TI  - Rheumatoid vasculitis - Case report.
AB  - Rheumatoid arthritis (RA) is a chronic systemic inflammatory autoimmune disease
      and its main manifestation is persistent synovitis affecting peripheral joints
      symmetrically, In spite of its destructive potential, the evolution of RA is
      highly variable. Some patients may have only a short-term process oligoarticular
      with minimum lesion, while others suffers a polyarthritis evolving with
      progressive and continuous involvement of other organ systems such as skin,
      heart, lungs, muscles and blood vessels rarely leading to rheumatoid vasculitis.
      The aim of this study was to describe a case of rheumatoid vasculitis a rare and
      severe condition. 

PMID- 25772655
TI  - [Devic's disease in an adolescent girl with juvenile dermatomyositis].
AB  - Devic's disease, also known as neuromyelitis optica, is an autoimmune
      inflammatory demyelinating disorder of the central nervous system that mainly
      affects the optic nerve and spinal cord. Recently, Devic's disease was
      demonstrated to be a channelopathy due to the presence of antibodies against the
      water channel aquaporin-4 in the blood-brain barrier. There have been reports of
      Devic's disease in infancy, but there are few reported associations of Devic's
      disease with other diseases. The association of Devic's disease with
      dermatomyositis has not yet been described in the literature. The aim of this
      paper is to describe the first case of Devic's disease in an adolescent with
      juvenile dermatomyositis.

PMID- 25772656
TI  - [Sleep quality in patients with ankylosing spondylitis].
AB  - INTRODUCTION: Ankylosing spondylitis (AS) is a chronic, inflammatory rheumatic
      disease characterized by the inflammation of the pelvis and spine that results in
      a restriction in the mobility of the spine. Due to the altered posture and
      nocturnal inflammatory pain, sleep disturbances are likely to occur in patients
      with AS. OBJECTIVE: This cross-sectional study aimed at determining the
      differences between the patients with AS and healthy controls in sleep quality,
      as well as assessing the relationship between the sleep quality and disease
      activity. METHOD: In order to assess sleep quality, fifty-five patients with AS
      (40 men, 15 women; mean age, 43 +/- 1 yrs) who fulfilled the modified New York
      criteria and fifty-five comparable controls (40 men, 15 women; mean age, 42 +/- 9
      yrs) completed the Pittsburgh Sleep Quality Index (PSQI) questionnaire. The
      disease activity was assessed by the Bath Ankylosing Spondylitis Disease Activity
      Index (BASDAI). RESULTS: Ankylosing spondylitis was associated with a
      significantly impaired sleep quality according to the total PSQI scores (p =
      0.001). Significant differences were found between the patients with AS and
      healthy controls in PSQI domains, including "subjective sleep quality" (p = 0.
      010), "sleep duration" (p = 0. 011), "habitual sleep efficiency" (p = 0. 034),
      "sleep disturbances" (p = 0. 003) and "daytime dysfunction" (p = 0. 009) but not
      in "sleep latency", "use of sleep medication". There was a significant positive
      correlation between the BASDAI and PSQI scores (r = 0.612, p = 0.001).
      CONCLUSION: In the current study, we found that the sleep disturbances were
      significantly higher in patients with AS in comparison to controls. Patients with
      active disease had worse sleep quality. In addition, disease activity was
      correlated with the scores of most of the PSQI subscales. Sleep quality
      assessment should be a tool for evaluating patients with AS.

PMID- 25772657
TI  - Translation and cross-cultural adaptation of FFI to Brazilian Portuguese version:
      FFI - Brazil.
AB  - OBJECTIVE: Perform the translation and cultural adaptation of the questionnaire
      Foot Functional Index (FFI), which assesses the functionality of the foot, to the
      Brazilian Portuguese version. METHOD: The Brazilian version development of FFI
      questionnaire was based on the guideline proposed by Guillemin. The applied
      process consisted of: (1) translation; (2) back-translation; (3) committee
      review; (4) pretesting. The Portuguese version was applied to 40 patients, both
      genders, aged over 18 years old, with plantar fasciitis and metatarsalgia to
      verify the level of the instrument comprehension. The final Brazilian version of
      the FFI was set after getting less than 15% of "not understanding" on each item.
      RESULTS: Some terms and expressions were changed to obtain cultural equivalence
      for FFI. The terms that were incomprehensible were changed in accordance of
      patient suggestions. CONCLUSION: After the translation and cultural adaptation of
      the questionnaire, the final Portuguese version of FFI was concluded.

PMID- 25772658
TI  - [Health related quality of life in Turkish polio survivors: impact of post-polio
      on the health related quality of life in terms of functional status, severity of
      pain, fatigue, and social, and emotional functioning].
AB  - OBJECTIVE: To determine the impact of postpolio-syndrome on quality of life in
      polio survivors. METHODS: Forty polio survivors were included in the study.
      Twenty-one patients fulfilling the Halstead's postpolio-syndrome criteria
      participated in postpolio-syndrome group. The remaining nineteen patients formed
      non-postpolio-syndrome group. Control group was composed of forty healthy
      subjects. Quality of life was evaluated by Nottingham Health Profile, depression
      by Beck Depression Scale and fatigue by Fatigue Symptom Inventory. Isometric
      muscle strength was measured by manual muscle testing. RESULTS: Total manual
      muscle testing score was 26.19+/-13.24 (median: 29) in postpolio-syndrome group
      and 30.08+/-8.9 (median: 32) in non-postpolio-syndrome group. Total manual muscle
      testing scores of non-postpolio-syndrome group were significantly higher than
      that of postpolio-syndrome group. Patients with postpolio-syndrome reported
      significantly higher levels of fatigue and reduced quality of life in terms of
      physical mobility, pain and energy when compared with patients without postpolio
      syndrome and control group. It was not reported a statistically significant
      difference in social and emotional functioning and sleep quality between
      postpolio-syndrome, non-postpolio-syndrome and control groups. Also it was not
      found any statistically significant difference in Beck Depression Scale scores
      among the groups. CONCLUSIONS: Postpolio-syndrome has a negative impact on
      quality of life in terms of functional status, severity of pain and energy. The
      identification, early recognition and rehabilitation of postpolio-syndrome
      patients may result in an improvement in their quality of life.

PMID- 25772659
TI  - Diagnosing vertebral fractures: missed opportunities.
AB  - Vertebral fractures are the single most common type of osteoporotic fracture.
      Postmenopausal women are at increased risk for osteoporotic vertebral fractures
      compared with women of childbearing age. Vertebral fractures are associated with
      an increase in morbidity, mortality, and high risk of a subsequent vertebral
      fracture, regardless of bone mineral density. Despite the common occurrence and
      serious consequences of vertebral fractures, they are often unrecognized or
      misdiagnosed by radiologists. Moreover, vertebral fractures may be described by
      variable terminology that can confuse rather than enlighten referring physicians.
      We conducted a survey of spine X-ray reports from a group of postmenopausal women
      screened for participation in a study of osteoporosis at Centro de Pesquisa
      Clinica do Brasil. A descriptive analysis evaluated the variability of reports in
      7 patients. Four independent general radiologists issued reports assessing
      vertebral fractures through a blinded analysis. The objective of this study was
      to evaluate for consistency in these reports. The analysis found marked
      variability in the diagnosis of vertebral fractures and the terminology used to
      describe them. In community medical practices, such variability could lead to
      differences in the management of patients with osteoporosis, with the potential
      for undertreatment or overtreatment depending on clinical circumstances. Accurate
      and unambiguous reporting of vertebral fractures is likely to be associated with
      improved clinical outcomes. 

PMID- 25772661
TI  - [Liver and spleen biometrics in childhood-onset systemic lupus erythematosus
      patients].
AB  - OBJECTIVE: To evaluate liver and spleen dimensions in childhood-onset systemic
      lupus erythematosus (c-SLE) patients and healthy controls. METHODS: 30 c-SLE
      patients and 30 healthy control volunteers underwent abdominal ultrasound. The
      following two liver measurements were performed in left hepatic lobe:
      craniocaudal and anteroposterior and three in right hepatic lobe (RHL): posterior
      craniocaudal (PCC-RHL), anterior craniocaudal and anteroposterior. Three spleen
      dimension measurements were also evaluated: longitudinal, transverse and
      anteroposterior. Demographic, clinical and laboratorial data, SLEDAI-2K, ECLAM,
      SLAM and treatment were assessed. RESULTS: Mean current age was similar in c-SLE
      and controls (170.31 +/- 27.81 vs. 164.15 +/- 39.25 months; p = 0.486). The mean
      of PCC-RHL dimension was significantly higher in c-SLE compared to controls
      (13.30 +/- 1.85 vs. 12.52 +/- 0.93, p = 0.044). There were no differences between
      the other hepatic biometrics and splenic parameters (p > 0.05). Further analysis
      in c-SLE patients according to PCC-RHL dimension >= 13.3cm versus < 13.3 cm
      showed that the median of SLEDAI-2K [8(0-18) vs. 2(0-8), p=0.004], ECLAM [4(0-9)
      vs. 2(0-5), p = 0.019] and SLAM [5(1-13) vs. 2(0-14), p = 0.016] were
      significantly higher in patients with higher PCC-RHL dimension, likewise the
      frequencie of nephritis (77% vs. 29%, p = 0.010). Liver enzymes were similar in
      both groups (p > 0.05). Positive correlation was observed between SLEDAI-2K and
      PCC-RHL (p = 0.001, r = +0.595). Negative correlation was evidenced between
      disease duration and longitudinal dimension of spleen (p = 0.031, r = -0.394).
      CONCLUSION: Our data raises the possibility that disease activity could lead to a
      subclinical and localized hepatomegaly during the disease course. Long disease
      duration resulted to spleen atrophy in c-SLE patients.

PMID- 25772662
TI  - Correlation of rheumatoid arthritis activity indexes (Disease Activity Score 28
      measured with ESR and CRP, Simplified Disease Activity Index and Clinical Disease
      Activity Index) and agreement of disease activity states with various cut-off
      points in a Northeastern Brazilian population.
AB  - INTRODUCTION: The Disease Activity Score 28 (DAS28) and its versions have been
      used to measure rheumatoid arthritis (RA) activity, but there is no consensus
      about which one is the best. OBJECTIVES: Determine the correlation among indexes
      (DAS28 ESR, DAS28 CRP, SDAI and CDAI) and evaluate agreement of activity strata
      using different cutoff points. METHODS: Rheumatoid arthritis patients were cross
      sectionally evaluated with data collection to calculate the DAS28 (ESR and CRP),
      SDAI and CDAI, using different cut-offs for defining remission, mild, moderate
      and high activity. Pearson correlations were calculated for continuous measures
      and agreement (kappa test) for the strata (remission, mild, moderate and high
      activity). RESULTS: Of 111 patients included, 108 were women, age 55.6 years, 11
      year disease duration. DAS28 (ESR) was significantly higher than DAS28 (CRP) (4.0
      vs. 3.5; p<0.001) and the values remained higher after stratification by age,
      gender, disease duration, rheumatoid factor and HAQ. Correlations among indexes
      ranged from 0.84 to 0.99, with better correlation between SDAI and CDAI.
      Agreements among activity strata ranged from 46.8% to 95.8%. DAS28 (CRP) with cut
      off point for the remission of 2.3 underestimated disease activity by 45.8%
      compared with DAS28 (ESR). SDAI and CDAI showed agreement of 95.8%. The four
      indexes were associated with disease duration and HAQ. CONCLUSIONS: Although the
      activity indexes show good correlation, they show discrepancies in activity
      strata, thus requiring more researches to define a better index and better cutoff
      points.

PMID- 25772663
TI  - [Evaluating the relation of premenstrual syndrome and primary dysmenorrhea in
      women diagnosed with fibromyalgia].
AB  - OBJECTIVE: In this study, we aimed to investigate the presence of premenstrual
      syndrome (PMS), primary dysmenorrhea (PD) and depression among women with
      fibromyalgia (FM) and healthy females and to determine possible factors related
      with PMS and PD in FM. METHOD: The present study was conducted on 98 female
      patients diagnosed with FM and 102 age and sex-matched healthy controls. All
      patients were evaluated for premenstrual syndrome (PMS) and primary dysmenorrhea
      (PD). Premenstrual syndrome was assessed among the patients for the presence of
      one or more affective or somatic symptoms within the five days preceding menses.
      The diagnosis of primary dysmenorrhea was defined as having abdominal pain or
      lower back pain lasting at least two days during a menstrual period. Dysmenorrhea
      was assessed via visual analog scale. Dysmenorrhea was rated via Multidimensional
      Scoring System. The Hamilton depression scale was applied to all patients.
      RESULTS: Primary dysmenorrhea was established in 41% of FM patients and 28% of
      the control group. A statistically significant difference was found in PD between
      the two groups (p=0.03). PMS was established in 42% of the FM patients and 25% of
      the control group. A statistically significant difference was found in PMS
      between the two groups (p=0.03). CONCLUSION: There is an increased frequency of
      premenstrual syndrome and dysmenorrhea in FM patients. The patients with high
      symptom severity scores and high depression scores among the FM patients are at
      risk of PMS and PD.

PMID- 25772664
TI  - [Current treatment and epidemiology of Clostridium difficile infections].
AB  - During the past 10years, Clostridium difficile infections (CDI) have become a
      major public health challenge. Their epidemiology has changed with a rise in the
      number of cases and an increase in severe episodes. Recurrence and failure of
      conventional treatments have become more common. Furthermore, a spread of CDI has
      been observed in the general population-involving subjects without the usual risk
      factors (unexposed to antibiotic treatment, young people, pregnant women, etc.).
      All these change are partially due to the emergence of the hypervirulent and
      hyperepidemic clone NAP1/B1/027. New therapeutic strategies (antimicrobial
      treatment, immunoglobulins, toxin chelation, fecal microbiota transplantation)
      are now available and conventional treatments (metronidazole and vancomycin) have
      been reevaluated with new recommendations. Recent studies show a better efficacy
      of vancomycin compared to metronidazole for severe episodes. Fidaxomicin is a
      novel antibiotic drug with interesting features, including an efficacy not
      inferior to vancomycin and a lower risk of recurrence. Finally, for multi
      recurrent forms, fecal microbiota transplantation seems to be the best option. We
      present the available data in this review. 

PMID- 25772665
TI  - Molecular diagnostics in soft tissue sarcomas and gastrointestinal stromal
      tumors.
AB  - Soft tissue sarcomas are rare malignant heterogenous tumors of mesenchymal origin
      with over fifty subtypes. The use of hematoxylin and eosin stained sections (and
      immunohistochemistry) in the morphologic assessment of these tumors has been the
      bane of clinical diagnosis until recently. The last decade has witnessed
      considerable progress in the understanding and application of molecular
      techniques in refining the current understanding of soft tissue sarcomas and
      gastrointestinal stromal tumors beyond the limits of traditional approaches.
      Indeed, the identification of reciprocal chromosomal translocations and fusion
      genes in some subsets of sarcomas with potential implications in the
      pathogenesis, diagnosis and treatment has been revolutionary. The era of
      molecular targeted therapy presents a platform that continues to drive biomarker
      discovery and personalized medicine in soft tissue sarcomas and gastrointestinal
      stromal tumors. In this review, we highlight how the different molecular
      techniques have enhanced the diagnosis of these tumors with prognostic and
      therapeutic implications.

PMID- 25772666
TI  - Incretin-based medications for type 2 diabetes: an overview of reviews.
AB  - AIMS: To summarize evidence from and assess the quality of published systematic
      reviews evaluating the safety, efficacy and effectiveness of incretin-based
      medications used in the treatment of type 2 diabetes. METHODS: We identified
      systematic reviews of randomized controlled trials or observational studies
      published in any language that evaluated the safety and/or effectiveness of
      glucagon-like peptide-1 (GLP-1) receptor agonists or dipeptidyl-peptidase-4 (DPP
      4) inhibitors. Data sources used include the Cochrane Library, PubMed, EMBASE,
      Web of Science, International Pharmaceutical Abstracts, table of contents of
      diabetes journals, and hand-searching of reference lists and clinical practice
      guidelines. The methodological quality of systematic reviews was independently
      assessed by two reviewers using the Assessment of Multiple Systematic Reviews
      (AMSTAR) checklist. Our study protocol was registered with PROSPERO
      (2013:CRD42013005149). The primary outcomes were pooled treatment effect
      estimates for glycaemic control, macrovascular and microvascular complications,
      and hypoglycaemic events. RESULTS: We identified 467 unique citations of which 84
      systematic reviews met our inclusion criteria. There were 51 reviews that
      evaluated GLP-1 receptor agonists and 64 reviews that evaluated DPP-4 inhibitors.
      The median (interquartile range) AMSTAR score was 6 (3) out of 11 for
      quantitative and 1 (1) for non-quantitative reviews. Among the 66 quantitative
      systematic reviews, there were a total of 718 pooled treatment effect estimates
      reported for our primary outcomes and 1012 reported pooled treatment effect
      estimates for secondary outcomes. CONCLUSIONS: Clinicians and policy makers, when
      using the results of systematic reviews to inform decision-making with regard to
      round clinical care or healthcare policies for incretin-based medications, should
      consider the variability in quality of reviews.

PMID- 25772667
TI  - Diurnal and seasonal variation of the brain serotonin system in healthy male
      subjects.
AB  - The mammalian circadian clock underlies both diurnal and seasonal changes in
      physiology, and its function is thought to be disturbed in both seasonal and non
      seasonal depression. In humans, molecular imaging studies have reported seasonal
      changes in the serotonin system. Despite the role of the circadian clock in
      generating seasonal physiological changes, however, diurnal variation of
      serotonin receptors and transporters has never been directly studied in humans.
      We used positron emission tomography to examine diurnal and seasonal changes in
      the serotonin 5-HT1A receptor and serotonin transporter in two large cohorts of
      healthy male subjects, employing a cross-sectional design. In 56 subjects
      measured with [(11)C]WAY-100635, we observed diurnal increases in the
      availability of 5-HT1A receptors in the cortex. In 40 subjects measured with
      [(11)C]MADAM, a decrease in 5-HTT was observed in the midbrain across the day. We
      also found seasonal changes in the 5-HT1A receptor in serotonin projection
      regions, with higher availability on days with a longer duration of daylight. Our
      observation that serotonin receptor and transporter levels may change across the
      day in humans is corroborated by experimental research in rodents. These findings
      have important implications for understanding the relationship between the
      circadian and serotonin systems in both the healthy brain and in affective
      disorders, as well as for the design of future molecular imaging studies. 

PMID- 25772668
TI  - Quantifying interindividual variability and asymmetry of face-selective regions:
      a probabilistic functional atlas.
AB  - Face-selective regions (FSRs) are among the most widely studied functional
      regions in the human brain. However, individual variability of the FSRs has not
      been well quantified. Here we use functional magnetic resonance imaging (fMRI) to
      localize the FSRs and quantify their spatial and functional variabilities in 202
      healthy adults. The occipital face area (OFA), posterior and anterior fusiform
      face areas (pFFA and aFFA), posterior continuation of the superior temporal
      sulcus (pcSTS), and posterior and anterior STS (pSTS and aSTS) were delineated
      for each individual with a semi-automated procedure. A probabilistic atlas was
      constructed to characterize their interindividual variability, revealing that the
      FSRs were highly variable in location and extent across subjects. The variability
      of FSRs was further quantified on both functional (i.e., face selectivity) and
      spatial (i.e., volume, location of peak activation, and anatomical location)
      features. Considerable interindividual variability and rightward asymmetry were
      found in all FSRs on these features. Taken together, our work presents the first
      effort to characterize comprehensively the variability of FSRs in a large sample
      of healthy subjects, and invites future work on the origin of the variability and
      its relation to individual differences in behavioral performance. Moreover, the
      probabilistic functional atlas will provide an adequate spatial reference for
      mapping the face network.

PMID- 25772669
TI  - Reliability of gait in multiple sclerosis over 6 months.
AB  - Gait impairment is ubiquitous in multiple sclerosis (MS) and is often
      characterized by alterations in spatiotemporal parameters of gait. There is
      limited information concerning reliability of spatiotemporal gait parameters over
      clinical timescales (e.g. 6 months). The current report provides novel evidence
      that gait parameters of 74 ambulatory persons with MS with mild-to-moderate
      disability are reliable over 6-months (ICC's for overall sample range from 0.56
      to 0.91) in the absence of any intervention above and beyond standard care. Such
      data can inform clinical decision-making and power analyses for designing RCTs
      (i.e., sample size estimates) involving persons with MS. 

PMID- 25772670
TI  - The "Thinking a Lot" Idiom of Distress and PTSD: An Examination of Their
      Relationship among Traumatized Cambodian Refugees Using the "Thinking a Lot"
      Questionnaire.
AB  - "Thinking a lot" (TAL)-also referred to as "thinking too much"-is a key complaint
      in many cultural contexts, and the current article profiles this idiom of
      distress among Cambodian refugees. The article also proposes a general model of
      how TAL generates various types of distress that then cause PTSD-type
      psychopathology, a model we refer to as the TAL-PTSD model. As tested in this
      Cambodian refugee sample, the model is supported by the following: (1) the close
      connection of TAL to PTSD as shown by odds ratio (OR = 19.6), correlation (r =
      .86), and factor loading; and (2) the mediation of most of the effect of TAL on
      PTSD by TAL-caused somatic symptoms, catastrophic cognitions, trauma recall,
      insomnia, and irritability. The questionnaire used in the present study is
      provided and can be used to examine TAL in other cultural and global contexts to
      advance the study of this commonly encountered distress form.

PMID- 25772671
TI  - A 25-year replication of Katz et al.'s (1988) metaphor norms.
AB  - Research in metaphor processing has made extensive use of the normed metaphor
      database created by Katz, Paivio, Marschark, & Clark (Metaphor and Symbolic
      Activity, 3, 191-214, 1988). Because of the plasticity of figurative language, we
      conducted a renorming of selected metaphors from the database on a new student
      population. Correlations between Katz et al.'s and the present data showed that
      the pattern of responses has remained highly consistent across time and
      populations. The consistency of the normative ratings allows us to be confident
      in future research that will use the Katz et al. collection. 

PMID- 25772672
TI  - Dendrimer-like hybrid particles with tunable hierarchical pores.
AB  - Dendrimer-like silica particles with a center-radial dendritic framework and a
      synergistic hierarchical porosity have attracted much attention due to their
      unique open three-dimensional superstructures with high accessibility to the
      internal surface areas; however, the delicate regulation of the hierarchical
      porosity has been difficult to achieve up to now. Herein, a series of dendrimer
      like amino-functionalized silica particles with tunable hierarchical pores (HPSNs
      NH2) were successfully fabricated by carefully regulating and optimizing the
      various experimental parameters in the ethyl ether emulsion systems via a one-pot
      sol-gel reaction. Interestingly, the simple adjustment of the stirring rate or
      reaction temperature was found to be an easy and effective route to achieve the
      controllable regulation towards center-radial large pore sizes from ca. 37-267
      (148 +/- 45) nm to ca. 8-119 (36 +/- 21) nm for HPSNs-NH2 with particle sizes of
      300-700 nm and from ca. 9-157 (52 +/- 28) nm to ca. 8-105 (30 +/- 16) nm for
      HPSNs-NH2 with particle sizes of 100-320 nm. To the best of our knowledge, this
      is the first successful regulation towards center-radial large pore sizes in such
      large ranges. The formation of HPSNs-NH2 may be attributed to the complex cross
      coupling of two processes: the dynamic diffusion of ethyl ether molecules and the
      self-assembly of partially hydrolyzed TEOS species and CTAB molecules at the
      dynamic ethyl ether-water interface of uniform small quasi-emulsion droplets.
      Thus, these results regarding the elaborate regulation of center-radial large
      pores and particle sizes not only help us better understand the complicated self
      assembly at the dynamic oil-water interface, but also provide a unique and ideal
      platform as carriers or supports for adsorption, separation, catalysis,
      biomedicine, and sensor. 

PMID- 25772673
TI  - Decreased postural control in adolescents born with extremely low birth weight.
AB  - The survival rates of infants born preterm with extremely low birth weight (ELBW
      <= 1000 g) have gradually improved over the last decades. However, these infants
      risk to sustain long-term disorders related to poor neurodevelopment. The
      objective was to determine whether adolescents born with ELBW have decreased
      postural control and stability adaptation. Twenty-nine ELBW subjects performed
      posturography with eyes open and closed under unperturbed and perturbed standing
      by repeated calf vibration. Their results were compared with twenty-one age- and
      gender-matched controls born after full-term pregnancy. The ELBW group had
      significantly decreased stability compared with controls in anteroposterior
      direction, both during the easier quiet stance posturography (p = 0.007) and
      during balance perturbations (p = 0.007). The ELBW group had similar stability
      decrease in lateral direction during balance perturbations (p = 0.013).
      Statistically, the stability decreases were similar with eyes closed and open,
      but proportionally larger with eyes open in both directions. Both groups
      manifested significant adaptation (p <= 0.023) to the balance perturbations in
      anteroposterior direction, though this adaptation process could not compensate
      for the general stability deficits caused by ELBW on postural control. Hence,
      adolescent survivors of ELBW commonly suffer long-term deficits in postural
      control, manifested as use of substantially more recorded energy on performing
      stability regulating high-frequency movements and declined stability with closed
      and open eyes both in anteroposterior and lateral direction. The determined
      relationship between premature birth and long-term functional deficits advocates
      that interventions should be developed to provide preventive care in neonatal
      care units and later on in life.

PMID- 25772674
TI  - Recombinant virus-like particles elicit protective immunity against avian
      influenza A(H7N9) virus infection in ferrets.
AB  - In March 2013, diagnosis of the first reported case of human infection with a
      novel avian-origin influenza A(H7N9) virus occurred in eastern China. Most human
      cases have resulted in severe respiratory illness and, in some instances, death.
      Currently there are no licensed vaccines against H7N9 virus, which continues to
      cause sporadic human infections. Recombinant virus-like particles (VLPs) have
      been previously shown to be safe and effective vaccines for influenza. In this
      study, we evaluated the immunogenicity and protective efficacy of a H7N9 VLP
      vaccine in the ferret challenge model. Purified recombinant H7N9 VLPs
      morphologically resembled influenza virions and elicited high-titer serum
      hemagglutination inhibition (HI) and neutralizing antibodies specific for
      A/Anhui/1/2013 (H7N9) virus. H7N9 VLP-immunized ferrets subsequently challenged
      with homologous virus displayed reductions in fever, weight loss, and virus
      shedding compared to these parameters in unimmunized control ferrets. H7N9 VLP
      was also effective in protecting against lung and tracheal infection. The
      addition of either ISCOMATRIX or Matrix-M1 adjuvant improved immunogenicity and
      protection of the VLP vaccine against H7N9 virus. These results provide support
      for the development of a safe and effective human VLP vaccine with potent
      adjuvants against avian influenza H7N9 virus with pandemic potential. 

PMID- 25772676
TI  - Alternative delivery of a thermostable inactivated polio vaccine.
AB  - In the near future oral polio vaccine (OPV) will be replaced by inactivated polio
      vaccine (IPV) as part of the eradication program of polio. For that reason, there
      is a need for substantial amount of safe and more affordable IPV for low-income
      countries. Bioneedles, which are biodegradable mini-implants, have the potential
      to deliver vaccines outside the cold-chain and administer them without the use of
      needles and syringes. In the current study, Bioneedles were filled with IPV,
      subsequently lyophilized, and antigenic recoveries were determined both directly
      after IPV-Bioneedle preparation as well as after elevated stability testing.
      Further, we assessed the immunogenicity of IPV-Bioneedles in rats and the
      residence time at the site of administration. Trivalent IPV was formulated in
      Bioneedles with recoveries of 101+/-10%, 113+/-18%, and 92+/-15%, respectively
      for serotypes 1, 2 and 3. IPV in Bioneedles is more resistant to elevated
      temperatures than liquid IPV: liquid IPV retained less than half of its
      antigenicity after 1 day at 45 degrees C and IPV in Bioneedles showed remaining
      recoveries of 80+/-10%, 85+/-4% and 63+/-4% for the three serotypes. In vivo
      imaging revealed that IPV administered via Bioneedles as well as subcutaneously
      injected liquid IPV showed a retention time of 3 days at the site of
      administration. Finally, an immunogenicity study showed that IPV-filled
      Bioneedles are able to induce virus-neutralizing antibody titers similar to those
      obtained by liquid intramuscular injection when administered in a booster regime.
      The addition of LPS-derivate PagL in IPV-filled Bioneedles did not increase
      immunogenicity compared to IPV-Bioneedles without adjuvant. The current study
      demonstrates the pre-clinical proof of concept of IPV-filled Bioneedles as a
      syringe-free alternative delivery system. Further pre-clinical and clinical
      studies will be required to assess the feasibility whether IPV-Bioneedles show
      sufficient safety and efficacy, and may contribute to the efforts to eradicate
      and prevent polio in the future. 

PMID- 25772675
TI  - An economic model assessing the value of microneedle patch delivery of the
      seasonal influenza vaccine.
AB  - BACKGROUND: New vaccine technologies may improve the acceptability, delivery
      (potentially enabling self-administration), and product efficacy of influenza
      vaccines. One such technology is the microneedle patch (MNP), a skin delivery
      technology currently in development. Although MNPs hold promise in preclinical
      studies, their potential economic and epidemiologic impacts have not yet been
      evaluated. METHODS: We utilized a susceptible-exposed-infectious-recovered (SEIR)
      transmission model linked to an economic influenza outcomes model to assess the
      economic value of introducing the MNP into the current influenza vaccine market
      in the United States from the third-party payer and societal perspectives. We
      also explored the impact of different vaccination settings, self-administration,
      the MNP price, vaccine efficacy, compliance, and MNP market share. Outcomes
      included costs, quality-adjusted life years (QALYs), cases, and incremental cost
      effectiveness ratios (ICERs; cost/QALY). RESULTS: With healthcare provider
      administration, MNP introduction would be cost-effective (ICERs <=$23,347/QALY)
      at all MNP price points ($9.50-$30) and market shares (10-60%) assessed, except
      when compliance and efficacy were assumed to be the same as existing vaccines and
      the MNP occupied a 10% market share. If MNP self-administration were available
      (assuming the same efficacy as current technologies), MNP compliance or its
      efficacy would need to increase by >=3% in order to be cost-effective (ICERs
      <=$1401/QALY), assuming a 2% reduction in administration success with
      unsupervised self-administration. Under these conditions, MNP introduction would
      be cost-effective for all price points and market shares assessed. CONCLUSIONS:
      When healthcare providers administered the MNP, its introduction would be cost
      effective or dominant (i.e., less costly and more effective) in the majority of
      scenarios assessed. If self-administration were available, MNP introduction would
      be cost-effective if it increased compliance enough to overcome any decrease in
      self-administration success or if the MNP presentation afforded an increase in
      efficacy over current delivery methods for influenza vaccines.

PMID- 25772677
TI  - Effect of Vitamin D Replacement on Atrial Electromechanical Delay in Subjects
      with Vitamin D Deficiency.
AB  - OBJECTIVES: Limited data are available regarding cardiac arrhythmias in vitamin D
      (VitD) deficiency. Therefore, we aimed to assess whether atrial electromechanical
      delay (AEMD) measured by tissue Doppler imaging (TDI), which is an indicator for
      atrial fibrillation (AF) development, is prolonged in patients with VitD
      deficiency as compared to the control group. The effect of vitD replacement on
      AEMD was also evaluated. METHODS: In this prospective study a total of 28 VitD
      deficient and 56 age-, gender-, and BMI-matched VitD-sufficient healthy
      participants were enrolled. P-wave dispersion (PWd) was calculated on the 12-lead
      electrocardiogram. Both intra- and inter-AEMD were calculated by TDI.
      Measurements were performed at baseline in both groups and were repeated after 6
      month replacement therapy in subjects with vitD deficiency. RESULTS: PWd and
      inter- and left intra-AEMD were significantly prolonged in patients with VitD
      deficiency compared to the control group (P < 0.001). While serum 25(OH)D levels
      were significantly and negatively correlated with left intra-AEMD (r = -0.657, P
      < 0.001), there was a positive correlation between serum 25(OH)D level and PWd (r
      = 0.523, P < 0.001). The serum 25(OH)D level was found as the independent
      predictor of the both left intra- and inter-AEMD in the multivariate linear
      regression analysis (beta:-0.552, P < 0.001 and beta:-0.555, P < 0.001,
      respectively). The serum 25(OH)D level was significantly increased after
      replacement therapy. While inter-AEMD was significantly decreased (P = 0.013),
      there was no change in PWD and left and right intra-AEMD (P > 0.05) following
      replacement therapy. CONCLUSION: PWd and left intra- and inter-AEMD are increased
      in patients with VitD deficiency. The serum 25(OH)D level was found as an
      independent predictor for AEMD in patients with VitD deficiency. Also a
      significant decrement was observed in inter-AEMD following vitD replacement
      therapy. Studies with longer follow-up are needed to investigate whether vitD
      deficient patients with prolonged AEMD develop clinical arrhythmia and vitD
      replacement reduces the risk of atrial arrhythmias.

PMID- 25772678
TI  - Impacts of varying light regimes on phycobiliproteins of Nostoc sp. HKAR-2 and
      Nostoc sp. HKAR-11 isolated from diverse habitats.
AB  - The adaptability of cyanobacteria in diverse habitats is an important factor to
      withstand harsh conditions. In the present investigation, the impacts of
      photosynthetically active radiation (PAR; 400-700 nm), ultraviolet-B (UV-B; 280
      315 nm), and PAR + UV-B radiations on two cyanobacteria viz., Nostoc sp. HKAR-2
      and Nostoc sp. HKAR-11 inhabiting diverse habitats such as hot springs and rice
      fields, respectively, were studied. Cell viability was about 14 % in Nostoc sp.
      HKAR-2 and <10 % in Nostoc sp. HKAR-11 after 48 h of UV-B exposure. PAR had
      negligible negative impact on the survival of both cyanobacteria. The continuous
      exposure of UV-B and PAR + UV-B showed rapid uncoupling, bleaching,
      fragmentation, and degradation in both phycocyanin (C-PC) and phycoerythrin (C
      PE) subunits of phycobiliproteins (PBPs). Remarkable bleaching effect of C-PE and
      C-PC was not only observed with UV-B or PAR + UV-B radiation, but longer period
      (24-48 h) of exposure with PAR alone also showed noticeable negative impact. The
      C-PE and C-PC subunits of the rice field isolate Nostoc sp. HKAR-11 were severely
      damaged in comparison to the hot spring isolate Nostoc sp. HKAR-2 with rapid
      wavelength shifting toward shorter wavelengths denoting the bleaching of both the
      accessory light harvesting pigments. The results indicate that PBPs of the hot
      spring isolate Nostoc sp. HKAR-2 were more stable under various light regimes in
      comparison to the rice field isolate Nostoc sp. HKAR-11 that could serve as a
      good source of valuable pigments to be used in various biomedical and
      biotechnological applications. 

PMID- 25772679
TI  - Growth-limiting proteins in maize coleoptiles and the auxin-brassinosteroid
      hypothesis of mesocotyl elongation.
AB  - The shoot of grass coleoptiles consists of the mesocotyl, the node, and the
      coleoptile (with enclosed primary leaf). Since the 1930s, it is known that auxin
      (indole-3-acetic acid, IAA), produced in the tip of the coleoptile, is the
      central regulator of turgor-driven organ growth. Fifty years ago, it was
      discovered that antibiotics that suppress protein biosynthesis, such as
      cycloheximide, inhibit auxin (IAA)-induced cell elongation in excised sections of
      coleoptiles and stems. Based on such inhibitor studies, the concept of "growth
      limiting proteins (GLPs)" emerged that was subsequently elaborated and modified.
      Here, we summarize the history of this idea with reference to IAA-mediated shoot
      elongation in maize (Zea mays) seedlings and recent studies on the molecular
      mechanism underlying auxin action in Arabidopsis thaliana. In addition, the
      analysis of light-induced inhibition of shoot elongation in intact corn seedlings
      is discussed. We propose a concept to account for the GLP-mediated epidermal wall
      loosening process in coleoptile segments and present a more general model of
      growth regulation in intact maize seedlings. Quantitative proteomic and genomic
      studies led to a refinement of the classic "GLP concept" to explain phytohormone
      mediated cell elongation at the molecular level (i.e., the recently proposed
      theory of a "central growth regulation network," CGRN). Novel data show that
      mesocotyl elongation not only depends on auxin but also on brassinosteroids
      (BRs). However, the biochemical key processes that regulate the IAA/BR-mediated
      loosening of the expansion-limiting epidermal wall(s) have not yet been
      elucidated.

PMID- 25772680
TI  - Stress-induced Oryza sativa BAT1 dual helicase exhibits unique bipolar
      translocation.
AB  - HLA-B associated transcript 1 (BAT1) protein, also named as spliceosome RNA
      helicase UAP56, is a member of the DExD/H-box family of helicases. However,
      regulation under stress, biochemical properties, and functions of plant homologue
      of BAT1 are poorly understood. Here, we report the purification and detailed
      biochemical characterization of the Oryza sativa homologue of BAT1 (OsBAT1/UAP56)
      protein (52 kDa) and regulation of its transcript under abiotic stress. OsBAT1
      transcript levels are enhanced in rice seedlings in response to abiotic stress
      including salt stress and abscisic acid. Purified OsBAT1 protein exhibits the DNA
      and RNA-dependent ATPase, RNA helicase, and DNA- and RNA-binding activities.
      Interestingly OsBAT1 also exhibits unique DNA helicase activity, which has not
      been reported so far in any BAT1 homologue. Moreover, OsBAT1 translocates in both
      the 3' to 5' and 5' to 3' directions, which is also a unique property. The K m
      value for OsBAT1 DNA helicase is 0.9753 nM and for RNA helicase is 1.7536 nM,
      respectively. This study demonstrates several unique characteristics of OsBAT1
      especially its ability to unwind both DNA and RNA duplexes; bipolar translocation
      and its transcript upregulation under abiotic stresses indicate that it is a
      multifunctional protein. Overall, this study represents significant contribution
      in advancing our knowledge regarding functions of OsBAT1 in RNA and DNA
      metabolism and its putative role in abiotic stress signaling in plants. 

PMID- 25772681
TI  - Ultrastructure of microsporogenesis and microgametogenesis in Brachypodium
      distachyon.
AB  - Brachypodium distachyon has emerged as a model system for forage grass and cereal
      grain species. Here, we report B. distachyon pollen development at the
      ultrastructural level. The process of microsporogenesis and microgametogenesis in
      B. distachyon follows the typical angiosperm pollen development sequence.
      Pronounced evaginations of the nuclear envelope are observed prior to meiosis,
      indicating active nucleocytoplasmic exchange processes. The microspore mother
      cells undergo meiosis and subsequent cytokinesis, forming isobilateral tetrads.
      Following dissolution of the callose wall and release of free and vacuolated
      microspores, mitotic divisions lead to the formation of mature, three-celled
      pollen grains. In B. distachyon, pollen wall formation begins at the tetrad stage
      by the formation of the exine template (primexine). The exine is tectate
      columellate, comprising a foot layer and endexine. Development of the tectum and
      the foot layer is complete by the free microspore stage of development, with the
      tectum formed discontinuously. The endexine initiates in the free microspore
      stage but becomes compressed in mature grains. The intine layer is deposited
      after mitosis and comprises three layers during the mature pollen stage of
      development. Pore development initiates during early free microspore development
      stage and Brachypodium pollen has a single germination pore consisting of a
      slightly raised annulus surrounding a central operculum. The tapetum is of the
      secretory type with loss of the tapetal cell walls beginning at about the time of
      microsporocyte meiosis. This is the first report on ultrastructure of
      microsporogenesis and microgametogenesis in B. distachyon. In general,
      Brachypodium microsporogenesis and microgametogenesis conform to a typical grass
      pollen development pattern. 

PMID- 25772682
TI  - Comparative floral spur anatomy and nectar secretion in four representatives of
      Ranunculaceae.
AB  - Nectaries are common in Ranunculaceae. These secretory structures, however, have
      not been studied in detail despite their importance in plant-animal interactions,
      and data relating to the structure of nectary spurs, which are so characteristic
      of several genera of this family, remain scarce. In order to redress this
      imbalance, we sought, in the present paper, to analyze the anatomical and
      ultrastructural organization of the nectary spurs of four representatives of
      Ranunculaceae, i.e., Aconitum lycoctonum L., Aquilegia vulgaris L., Consolida
      regalis Gray, and Delphinium elatum L. Nectary spurs were examined using light,
      fluorescence, scanning electron, and transmission electron microscopy. The floral
      nectaries of A. lycoctonum and A. vulgaris are situated at the apices of the
      spurs, whereas in C. regalis and D. elatum, the nectary is located along the
      floor surface of the spurs. Nectar in C. regalis and D. elatum is exuded through
      micro-channels in the cuticle, whereas in A. lycoctonum and A. vulgaris, it is
      released by means of cell wall disruption, indicating that the method of nectar
      secretion here is holocrine. Structurally, the nectary of all four investigated
      species is quite similar, and its cells are typical of nectar-producing cells
      described in the literature. It is proposed that in A. lycoctonum and A.
      vulgaris, disruption of the cell wall and the release of the entire cell contents
      into the spur cavity contribute to the composition of the nectar that the latter
      contains, enriching it with cytoplasmic components. We conclude that the manner
      of nectar exudation may vary considerably between closely related plant species,
      regardless of their geographical origin and phylogeny. 

PMID- 25772683
TI  - Effects of copper and lead exposure on the ecophysiology of the brown seaweed
      Sargassum cymosum.
AB  - The effects of the heavy metals copper (Cu) and lead (Pb) on Sargassum cymosum
      were evaluated by determining uptake capacity, growth rates, photosynthetic
      efficiency, contents of photosynthetic pigments and phenolic compounds, 2,2
      diphenyl-1-picrylhydrazyl radical-scavenging capacity, and morphological and
      cellular changes. S. cymosum was cultivated with Cu and Pb separately and
      combined at concentrations of 10, 25, and 50 MUM for 7 days in laboratory
      controlled conditions. Seaweeds under Cu treatment showed the highest biosorption
      capacity, and growth rates were significantly reduced compared to the control.
      The photosynthesis/irradiance curves showed alterations in kinetic patterns in
      the metal-treated samples. Specifically, Cu treatment alone inhibited electron
      transport rate (ETR) response, while Pb alone induced it. However, samples
      treated with both Cu and Pb (Cu + Pb) showed inhibition in ETR. The total amount
      of pigments increased relative to control. Light microscopy showed an increase in
      phenolic compounds, with physodes migrating towards cortical cells. Scanning
      electronic microscopy revealed alterations in the typical rough surface of
      thallus, when compared with control, especially for Pb treatments. Based on these
      results, it could be concluded that Cu and Pb are stress factors for S. cymosum,
      promoting alterations in seaweed metabolism and stimulating protective mechanisms
      against oxidative stress. However, the high bioaccumulation capacity of both
      heavy metals indicates a possible application for S. cymosum as a biosorbent
      agent for contaminated wastewater when metals are in low concentrations.

PMID- 25772684
TI  - Microbial sealants do not decrease surgical site infection for clean-contaminated
      colorectal procedures.
AB  - BACKGROUND: Surgical site infections (SSI) are costly complications that may
      cause significant morbidity and increase the cost of care, particularly in
      colorectal surgery. Microbial sealants (MS) are a new class of wound barriers
      aimed at decreasing SSI; however, there is only evidence of benefit in clean
      class 1 procedures. Based on its success in class 1 procedures, we hypothesized
      that a microbial sealant could reduce the rate of SSI by half for clean
      contaminated colorectal procedures (class 2). METHODS: This was a single
      institution, multihospital, prospective, randomized study approved by the
      institutional review board. The primary objective was to determine the rate of
      SSI when microbial sealant (InteguSeal(c) Kimberly-Clark) is used compared to
      control (no microbial sealant). Data collected included: open versus laparoscopy,
      age, body mass index (BMI), diabetes and morbidity [American Society of
      Anesthesiologists (ASA) class], hospital readmission, reoperation and wound
      dehiscence. Enrolled subjects received the same preoperative mechanical bowel
      preparation with oral antibiotics, operative skin preparation (Chloraprep),
      Surgical Care Improvement Project guidelines implementation), and postoperative
      care glycemic control for diabetics. RESULTS: A total of 100 subjects were
      recruited over 15 months (MS-50; no MS-50). The overall incidence of SSI was 12
      %, 14 % (7/50) in the MS versus 10 % (5/50) in the no MS group (p = 0.545). SSI
      incidence with and without microbial sealant was not significantly different in
      either the open or the laparoscopic subgroup. Laparoscopy decreased absolute risk
      of SSI by 16 %. Secondary data (age, BMI, diabetes, ASA) and tertiary data
      (readmission, reoperation, wound dehiscence) were positively correlated with SSI.
      CONCLUSIONS: Microbial sealant as employed in this study did not appear to offer
      any benefit in a class 2 (clean contaminated) operative procedure when
      perioperative care is standardized. The relative benefit of laparoscopy was also
      confirmed but unaffected by use of the microbial sealant.

PMID- 25772685
TI  - Prospective multicenter observational trial on the safety and efficacy of
      LEVORAG(r) Emulgel in the treatment of acute and chronic anal fissure.
AB  - BACKGROUND: Anal fissure (AF) is a common cause of anal pain with a tendency not
      to heal spontaneously because of ischemia of the anoderm caused by sphincter
      spasm. Lateral internal sphincterotomy, while very effective, can cause fecal
      incontinence and chemical sphincterotomy by application of cream may have
      discouraging side effects and/or low efficacy. The aim of this prospective
      multicenter study was to evaluate the safety and effectiveness of a new medical
      treatment based on Emulgel cream, with emollient, soothing and protective agents,
      on AF healing. METHODS: Consecutive patients with AF treated in nine
      coloproctology units during 6 months entered the study on topical treatment with
      Levorag((r)) Emulgel (THD S.p.A Correggio (RE), Italy). Before treatment, they
      had a proctologic examination and pain was measured using a visual analog scale.
      THD Levorag((r)) Emulgel was applied every 12 h for 40 days. Monitoring was
      scheduled at 10, 20 and 40 days. At time 0 and at the end of treatment, patients
      underwent anorectal manometry, if possible. RESULTS: Two hundred eighty-four AF
      patients were recruited (171 acute fissures). Complete healing was achieved in
      47.9 % of the cases, an improvement in 31.0 % (global efficacy 78.9 %). In
      patients with acute fissure, the rate of efficacy was 89.4 % (complete healing:
      64.3 %, improvement: 25.1 %), in those with chronic fissure the rate of efficacy
      was 62.8 % (complete healing: 23 %, improvement: 39.8 %), p < 0.001. Pain and
      resting anal pressure decreased significantly after treatment. CONCLUSIONS:
      Treatment with THD Levorag((r)) Emulgel proved to be effective for the
      reepithelization of AF and the reduction of pain in the short term in about 80 %
      of patients.

PMID- 25772686
TI  - Effect of depressive and anxiety symptoms during pregnancy on risk of obstetric
      interventions.
AB  - AIM: The effect of prenatal mental health on the risk of obstetric interventions
      is unclear. The present study examined the associations between depressive and
      anxiety symptoms in the second and third trimesters and mode of delivery,
      epidural use and labor induction in a large community-based pregnancy cohort, in
      Alberta, Canada. MATERIAL AND METHODS: Women who had singleton pregnancies,
      delivered in hospital, and had medical data were selected (n = 2825). Obstetric
      intervention data were obtained from the medical records, and depressive and
      anxiety symptoms were measured by the Edinburgh Postnatal Depression Scale and
      the Spielberger State Anxiety Inventory. Data were evaluated with multivariate
      multinomial and logistic regression analyses using a hierarchical modeling.
      RESULTS: After accounting for factors known to increase the risk of each
      intervention, including demographic variables, smoking, hospital site,
      gestational age, previous history of cesarean delivery, prepregnancy body mass
      index, assisted conception, and antepartum risk score, the only mental health
      variable associated with obstetric interventions was depressive symptoms in the
      third trimester, which increased the risk of emergency cesarean delivery
      (adjusted odds ratio, 2.04; 95% confidence interval, 1.26-3.29). No associations
      were found between antenatal depressive and anxiety symptoms and other obstetric
      interventions. CONCLUSION: The present findings support an association between
      depressive symptoms and adverse obstetric outcomes and suggest that anxiety and
      depression may have different effects on obstetric outcomes. Understanding the
      mechanism in which depression increases the risk of emergency cesarean birth
      needs further research.

PMID- 25772687
TI  - Highly efficient cell-type-specific gene inactivation reveals a key function for
      the Drosophila FUS homolog cabeza in neurons.
AB  - To expand the rich genetic toolkit of Drosophila melanogaster, we evaluated
      whether introducing FRT or LoxP sites in endogenous genes could allow for cell
      type-specific gene inactivation in both dividing and postmitotic cells by GAL4
      driven expression of FLP or Cre recombinase. For proof of principle, conditional
      alleles were generated for cabeza (caz), the Drosophila homolog of human FUS, a
      gene implicated in the neurodegenerative disorders amyotrophic lateral sclerosis
      (ALS) and frontotemporal dementia (FTD). Upon selective expression in neurons or
      muscle, both FLP and Cre mediated caz inactivation in all neurons or muscle
      cells, respectively. Neuron-selective caz inactivation resulted in failure of
      pharate adult flies to eclose from the pupal case, and adult escapers displayed
      motor performance defects and reduced life span. Due to Cre-toxicity, FLP/FRT is
      the preferred system for cell-type-specific gene inactivation, and this strategy
      outperforms RNAi-mediated knock-down. Furthermore, the GAL80 target system
      allowed for temporal control over gene inactivation, as induction of FLP
      expression from the adult stage onwards still inactivated caz in >99% of neurons.
      Remarkably, selective caz inactivation in adult neurons did not affect motor
      performance and life span, indicating that neuronal caz is required during
      development, but not for maintenance of adult neuronal function. 

PMID- 25772688
TI  - Vasculogenesis and angiogenesis in nonseminomatous testicular germ cell tumors.
AB  - Testicular germ cell tumors (TGCTs) comprise the vast majority of all testicular
      malignancies and are the most common type of cancer among young male adults. The
      nonseminomatous variant of TGCTs is characterized by the presence of embryonic
      and extraembryonic tissues together with a population of pluripotent cancer stem
      cells, the so-called embryonal carcinoma. One of the main causes of the
      resistance of these tumors to therapy is their ability to invade adjacent tissues
      and metastasize into distant sites of the body. Both of these tumor processes are
      highly favored by the neovascularization of the malignant tissue. New vessels can
      be generated by means of angiogenesis or vasculogenesis, and both have been
      observed to occur during tumor vascularization. Nevertheless, the precise
      contribution of each process to the neoplastic vascular bed of TGCTs remains
      unknown. In addition, another process known as tumor-derived vasculogenesis, in
      which malignant cells give rise to endothelial cells, has also been reported to
      occur in a number of tumor types, including experimental TGCTs. The participation
      and cross talk of these 3 processes in tumor vascularization is of particular
      interest, given the embryonic origin of teratocarcinomas. Thus, in the present
      review, we discuss the importance of all 3 vascularization processes in the
      growth, invasion, and metastasis of testicular teratocarcinomas and summarize the
      current state of knowledge of the TGCT microenvironment and its relationship with
      vascularization. Finally, we discuss the importance of vascularization as a
      therapeutic target for this type of malignancy. 

PMID- 25772689
TI  - Sexual dimorphism in the early embryogenesis of the chicken (Gallus Gallus
      domesticus).
AB  - Studies of dioecious animals suggest that sex-specific development occurs from
      the onset of embryogenesis. This must be accounted for when addressing issues
      involving sex-ratio regulation in domestic animals and conservation biology. We
      investigated the occurrence of growth-rate sexual dimorphism in 84 chicken
      embryos incubated for 30 hr and nucleic-acid abundance in 99 embryos incubated
      for 4 hr. Comparative expression of the genes engaged in cell-cycle regulation
      (16 genes), embryo growth (10 genes), metabolic activity (2 genes), and
      epigenetic regulation (4 genes) in 4-hr male and female embryos were further
      analyzed by reverse-trancriptase quantitative PCR. At the stage when somite
      structure commences, males are growing faster than females. DNA and RNA yields at
      4 hr are elevated in males compared to females, and most cell-proliferation
      promoting genes are overexpressed in males. Expression of key metabolic genes
      (G6PD and HPRT) and the principal genes responsible for DNA methylation (DNMTs),
      however, does not differ between the sexes. These data suggest that the faster
      growth of early male embryos is conserved among mammalian and bird phyla, and may
      have an evolutionary importance.

PMID- 25772690
TI  - High motility group box 1 (HMGB1) protein and its receptor for advanced glycation
      end products (RAGE) expression in chronic rhinosinusitis without nasal polyps.
AB  - INTRODUCTION: Chronic rhinosinusitis (CRS) affects 14% of the world population.
      The high motility group box 1 (HMGB1) protein triggers inflammation, cell
      proliferation and cell survival through its receptor for advanced glycation end
      products (RAGE) upon release from stressed or necrotic cells. The aim of the
      study was to analyze the expression and function of HMGB1 and RAGE in CRS,
      providing more information about HMGB1 signaling pathway in CRS, to determine its
      potential clinical significance. MATERIAL AND METHODS: Thirty-seven patients with
      CRS and 26 normal controls (NC) were enrolled in this study. Classification of
      disease severity using the SNOT-20 questionnaire, nasal endoscopy, CT scan,
      assessment of allergy status, microbiological and cytological analysis was
      performed in patients. Fresh sinus mucosa samples were obtained and analyzed by
      immunohistochemistry for HMGB1 and RAGE expression in epithelial cells. ELISA
      assay was performed to evaluate the concentration of HMGB1 in the patients' sera.
      RESULTS: No differences were found in HMGB1 immunoexpression between CRS patients
      and NC, however there was a highly significant difference in RAGE
      immunoexpression between both groups. There was a correlation between RAGE
      expression and number of tissue-infiltrating lymphocytes. Further, RAGE
      expression positively correlated with disease severity and a positive history for
      allergies. CONCLUSIONS: Interaction of HMGB1 and RAGE might be relevant to CRS
      pathomechanisms leading to sinus mucosa hyperproliferation. CRS pathogenesis
      might be especially related to the RAGE overexpression correlated with disease
      severity and allergy.

PMID- 25772691
TI  - Would raising tobacco tax in China unfairly burden the poor?

PMID- 25772692
TI  - The consequences of tobacco tax on household health and finances in rich and poor
      smokers in China: an extended cost-effectiveness analysis.
AB  - BACKGROUND: In China, there are more than 300 million male smokers. Tobacco
      taxation reduces smoking-related premature deaths and increases government
      revenues, but has been criticised for disproportionately affecting poorer people.
      We assess the distributional consequences (across different wealth quintiles) of
      a specific excise tax on cigarettes in China in terms of both financial and
      health outcomes. METHODS: We use extended cost-effectiveness analysis methods to
      estimate, across income quintiles, the health benefits (years of life gained),
      the additional tax revenues raised, the net financial consequences for
      households, and the financial risk protection provided to households, that would
      be caused by a 50% increase in tobacco price through excise tax fully passed onto
      tobacco consumers. For our modelling analysis, we used plausible values for key
      parameters, including an average price elasticity of demand for tobacco of -0.38,
      which is assumed to vary from -0.64 in the poorest quintile to -0.12 in the
      richest, and we considered only the male population, which constitutes the
      overwhelming majority of smokers in China. FINDINGS: Our modelling analysis
      showed that a 50% increase in tobacco price through excise tax would lead to 231
      million years of life gained (95% uncertainty range 194-268 million) over 50
      years (a third of which would be gained in the lowest income quintile), a gain of
      US$703 billion ($616-781 billion) of additional tax revenues from the excise tax
      (14% of which would come from the lowest income quintile, compared with 24% from
      the highest income quintile). The excise tax would increase overall household
      expenditures on tobacco by $376 billion ($232-505 billion), but decrease these
      expenditures by $21 billion (-$83 to $5 billion) in the lowest income quintile,
      and would reduce expenditures on tobacco-related disease by $24.0 billion ($17.3
      26.3 billion, 28% of which would benefit the lowest income quintile). Finally, it
      would provide financial risk protection worth $1.8 billion ($1.2-2.3 billion),
      mainly concentrated (74%) in the lowest income quintile. INTERPRETATION:
      Increased tobacco taxation can be a pro-poor policy instrument that brings
      substantial health and financial benefits to households in China. FUNDING: Bill &
      Melinda Gates Foundation and Dalla Lana School of Public Health.

PMID- 25772693
TI  - Psychometric Evaluation of the Caregiving Competence Scale Among Chinese Family
      Caregivers.
AB  - PURPOSE: The aim of the study was to develop a Chinese version of the Caregiving
      Competence Scale (CCS) and evaluate its psychometric properties. DESIGN: A
      multicenter, cross-sectional study design. METHODS: Brislin's translation method
      was used to translate the CCS into Chinese. Its psychometric properties were
      tested with 118 Chinese family caregivers of stroke survivors. FINDINGS: The
      Chinese version of the Caregiving Competence Scale (CCS-C) demonstrated adequate
      internal consistency (Cronbach's alpha = .81) and stability (weighted kappa
      statistics: .67-.78). Convergent and discriminative validities were supported by
      a significant correlation between the CCS-C and the General Self-Efficacy Scale
      scores (r = .46, p < .01) and a significant difference in the CCS-C scores
      between depressed and nondepressed caregivers (p = .03), respectively.
      CONCLUSIONS: Study results suggested that the CCS-C could be a valid and reliable
      self-reported instrument for family caregivers of Chinese stroke survivors.
      CLINICAL RELEVANCE: This scale can be used to evaluate the caregiving competence
      of stroke caregivers in nursing research and in clinical settings.

PMID- 25772694
TI  - Meloxicam inhibits fipronil-induced apoptosis via modulation of the oxidative
      stress and inflammatory response in SH-SY5Y cells.
AB  - Oxidative stress and inflammatory responses have been identified as key elements
      of neuronal cell apoptosis. In this study, we investigated the mechanisms by
      which inflammatory responses contribute to apoptosis in human neuroblastoma SH
      SY5Y cells treated with fipronil (FPN). Based on the cytotoxic mechanism of FPN,
      we examined the neuroprotective effects of meloxicam against FPN-induced neuronal
      cell death. Treatment of SH-SY5Y cells with FPN induced apoptosis via activation
      of caspase-9 and -3, leading to nuclear condensation. In addition, FPN induced
      oxidative stress and increased expression of cyclooxygenase-2 (COX-2) and tumor
      necrosis factor-alpha (TNF-alpha) via inflammatory stimulation. Pretreatment of
      cells with meloxicam enhanced the viability of FPN-exposed cells through
      attenuation of oxidative stress and inflammatory response. FPN activated mitogen
      activated protein kinase (MAPK) and inhibitors of MAPK abolished FPN-induced COX
      2 expression. Meloxicam also attenuated FPN-induced cell death by reducing MAPK
      mediated pro-inflammatory factors. Furthermore, we observed both nuclear
      accumulation of p53 and enhanced levels of cytosolic p53 in a concentration
      dependent manner after FPN treatment. Pretreatment of cells with meloxicam
      blocked the translocation of p53 from the cytosol to the nucleus. Together, these
      data suggest that meloxicam may exert anti-apoptotic effects against FPN-induced
      cytotoxicity by both attenuating oxidative stress and inhibiting the inflammatory
      cascade via inactivation of MAPK and p53 signaling.

PMID- 25772696
TI  - Variation by center and economic burden of readmissions after liver
      transplantation.
AB  - The rate and causes of hospital readmissions after liver transplantation (LT)
      remain largely unknown in the United States. Adult patients (n = 11,937; 43.1% of
      all LT cases) undergoing LT from 2007 to 2011 were examined with a linkage of the
      University HealthSystem Consortium and Scientific Registry of Transplant
      Recipients databases to determine the incidence and risk factors for 30-day
      readmissions and utilization metrics 90 days after LT. The overall 30-day
      hospital readmission rate after LT was 37.9%, with half of patients admitted
      within 7 days after discharge. Readmitted patients had worse overall graft and
      patient survival with a 2-year follow-up. Multivariate analysis identified risk
      factors associated with 30-day hospital readmission, including a higher Model for
      End-Stage Liver Disease score, diabetes at LT, dialysis dependence, a high donor
      risk index allograft, and discharge to a rehabilitation facility. After
      adjustments for donor, recipient, and geographic factors in a hierarchical model,
      we found significant variation in readmission rates among hospitals ranging from
      26.3% to 50.8% (odds ratio, 0.53-1.90). In the 90-day analysis after LT,
      readmissions accounted for $43,785 of added costs in comparison with patients who
      were not readmitted in the first 90 days. This is the first national report
      showing that more than one-third of LT recipients are readmitted to their center
      within 30 days and that readmissions are associated with center variation and
      increased resource utilization.

PMID- 25772695
TI  - The standardization of terminology of lower urinary tract function in children
      and adolescents: Update report from the standardization committee of the
      International Children's Continence Society.
AB  - AIM: The impact of the original International Children's Continence Society
      (ICCS) terminology document on lower urinary tract (LUT) function resulted in the
      global establishment of uniformity and clarity in the characterization of LUT
      function and dysfunction in children across multiple healthcare disciplines. The
      present document serves as a stand-alone terminology update reflecting refinement
      and current advancement of knowledge on pediatric LUT function. METHODS: A
      variety of worldwide experts from multiple disciplines within the ICCS leadership
      who care for children with LUT dysfunction were assembled as part of the
      standardization committee. A critical review of the previous ICCS terminology
      document and the current literature was performed. Additionally, contributions
      and feedback from the multidisciplinary ICCS membership were solicited. RESULTS:
      Following a review of the literature over the last 7 years, the ICCS experts
      assembled a new terminology document reflecting current understanding of bladder
      function and LUT dysfunction in children using the resources from the literature
      review, expert opinion and ICCS member feedback. CONCLUSIONS: The present ICCS
      terminology document provides a current and consensus update to the evolving
      terminology and understanding of LUT function in children. Neurourol. Urodynam.
      35:471-481, 2016. (c) 2015 Wiley Periodicals, Inc.

PMID- 25772697
TI  - The genetic architecture of the human immune system: a bioresource for
      autoimmunity and disease pathogenesis.
AB  - Despite recent discoveries of genetic variants associated with autoimmunity and
      infection, genetic control of the human immune system during homeostasis is
      poorly understood. We undertook a comprehensive immunophenotyping approach,
      analyzing 78,000 immune traits in 669 female twins. From the top 151 heritable
      traits (up to 96% heritable), we used replicated GWAS to obtain 297 SNP
      associations at 11 genetic loci, explaining up to 36% of the variation of 19
      traits. We found multiple associations with canonical traits of all major immune
      cell subsets and uncovered insights into genetic control for regulatory T cells.
      This data set also revealed traits associated with loci known to confer
      autoimmune susceptibility, providing mechanistic hypotheses linking immune traits
      with the etiology of disease. Our data establish a bioresource that links genetic
      control elements associated with normal immune traits to common autoimmune and
      infectious diseases, providing a shortcut to identifying potential mechanisms of
      immune-related diseases.

PMID- 25772698
TI  - Feedback from network states generates variability in a probabilistic olfactory
      circuit.
AB  - Variability is a prominent feature of behavior and is an active element of
      certain behavioral strategies. To understand how neuronal circuits control
      variability, we examined the propagation of sensory information in a chemotaxis
      circuit of C. elegans where discrete sensory inputs can drive a probabilistic
      behavioral response. Olfactory neurons respond to odor stimuli with rapid and
      reliable changes in activity, but downstream AIB interneurons respond with a
      probabilistic delay. The interneuron response to odor depends on the collective
      activity of multiple neurons-AIB, RIM, and AVA-when the odor stimulus arrives.
      Certain activity states of the network correlate with reliable responses to odor
      stimuli. Artificially generating these activity states by modifying neuronal
      activity increases the reliability of odor responses in interneurons and the
      reliability of the behavioral response to odor. The integration of sensory
      information with network states may represent a general mechanism for generating
      variability in behavior.

PMID- 25772700
TI  - Donor-specific HLA-antibodies: the difficulty of separating the wheat from the
      chaff.

PMID- 25772702
TI  - Entrapment of a pulmonary artery catheter inside a knotted percutaneous sheath
      introducer.

PMID- 25772703
TI  - Thoracoscopic visualization of a misdirected paravertebral catheter.

PMID- 25772701
TI  - Randomized controlled trial of gabapentin as an adjunct to perioperative
      analgesia in total hip arthroplasty patients.
AB  - PURPOSE: Gabapentin was investigated as a single-dose adjunct to morphine for
      postoperative pain management. The primary objective was to determine if
      gabapentin given preoperatively and for two days postoperatively as part of
      multimodal analgesia would decrease postoperative morphine consumption in
      patients undergoing primary total hip arthroplasty (THA). METHODS: The study
      group included 102 patients aged 19-90 years who were undergoing primary THA in a
      single joint with no contraindications to the study medications, no chronic pain
      syndrome, and no chronic opioid use. Intervention group patients (n = 48)
      received gabapentin 600 mg po preoperatively and 200 mg postoperatively on the
      day of surgery. They were continued on gabapentin at 200 mg three times daily for
      two days. Control group patients (n = 54) received placebo in a similar fashion.
      Preoperatively, all patients were given 30 mg of ketorolac intravenously and
      acetaminophen 1000 mg po. Postoperatively, they received intravenous patient
      controlled analgesia with morphine, along with ketorolac 15 mg iv and
      acetaminophen 1000 mg po every six hours. RESULTS: The primary outcome was mean
      (SD) postoperative morphine consumption at 72 hr which was 55.8 (39.2) mg in the
      gabapentin groups vs 60.7 (37.2) mg for the control group (mean difference, -4.91
      mg, 95% confidence intervals [CI]: -21.2 to 11.35; P = 0.550). There were no
      significant differences between the groups regarding secondary outcomes: pain
      scores, side effects, range of motion. Patient satisfaction on day 3 was more
      favourable in the placebo group. Length of hospitalization was marginally shorter
      in the placebo group. CONCLUSIONS: This trial indicated that gabapentin treatment
      had no clinically important reduction in postoperative morphine consumption at 72
      hr in patients undergoing THA. Multimodal analgesia may account for the similar
      primary and secondary outcomes found in the groups. This trial was registered at
      ClinicalTrials.gov, number: NCT01307202.

PMID- 25772704
TI  - Development and laboratory evaluation of a real-time PCR assay for detecting
      viruses and bacteria of relevance for community-acquired pneumonia.
AB  - Community-acquired pneumonia may present with similar clinical symptoms,
      regardless of viral or bacterial cause. Diagnostic assays are needed to rapidly
      discriminate between causes, because this will guide decisions on appropriate
      treatment. Therefore, a quantitative real-time PCR (qPCR) assay with duplex
      reactions targeting eight bacteria and six viruses was developed. Technical
      performance was examined with linear plasmids. Upper and lower respiratory tract
      specimens were used to compare the qPCR assay with standard microbiological
      methods. The limit of detection was 5 to 20 DNA template copies with
      approximately 1000-fold differences in concentrations of the two competing
      templates. SDs for positive controls were <5%. The use of the qPCR assay resulted
      in 113 positive identifications in 94 respiratory specimens compared with 38 by
      using standard diagnostics. Diagnostic accuracy of the qPCR assay varied between
      60% positive agreement with standard tests for Streptococcus pneumoniae and 100%
      for Mycoplasma pneumoniae, Moraxella catarrhalis, and Staphylococcus aureus.
      Negative percentage of agreement was >95% for M. pneumoniae, Streptococcus
      pyogenes, respiratory syncytial virus, and influenza A virus; whereas it was only
      56% for Haemophilus influenzae. Multiple microbial agents were identified in 19
      of 44 sputum and 19 of 50 nasopharynx specimens. We conclude that in parallel
      qPCR detection of the targeted respiratory bacteria and viruses is feasible. The
      results indicate good technical performance of the assay in clinical specimens. 

PMID- 25772706
TI  - A facile and versatile approach to double N-heterohelicenes: tandem oxidative C-N
      couplings of N-Heteroacenes via cruciform dimers.
AB  - Novel double N-hetero[5]helicenes that are composed of two nitrogen-substituted
      heteropentacenes are synthesized by tandem oxidative C?N couplings via the
      cruciform heteropentacene dimers. The developed method is very facile and enables
      the synthesis of a double helicene in only two steps from commercially available
      naphthalene derivatives. These double N-hetero[5]helicenes have larger torsion
      angles in the fjord regions than typical [5]helicenes, and
      optical/electrochemical measurements revealed a significant increase in the
      electronic communication between the two heteropentacene moieties of the double
      helicenes compared with their cruciform dimers. The optical resolution of one of
      the double helicenes was successfully carried out, and their stability towards
      racemization was remarkably higher than those of typical [5]helicenes. The
      synthetic strategy proposed in this paper should be versatile and widely
      applicable to the preparation of double helicenes from other N-containing pi
      conjugated planar molecules. 

PMID- 25772705
TI  - Enhanced ratio of signals enables digital mutation scanning for rare allele
      detection.
AB  - The use of droplet digital PCR (ddPCR) for low-level DNA mutation detection in
      cancer, prenatal diagnosis, and infectious diseases is growing rapidly. However,
      although ddPCR has been implemented successfully for detection of rare mutations
      at pre-determined positions, no ddPCR adaptation for mutation scanning exists.
      Yet, frequently, clinically relevant mutations reside on multiple sequence
      positions in tumor suppressor genes or complex hotspot mutations in oncogenes.
      Here, we describe a combination of coamplification at lower denaturation
      temperature PCR (COLD-PCR) with ddPCR that enables digital mutation scanning
      within approximately 50-bp sections of a target amplicon. Two FAM/HEX-labeled
      hydrolysis probes matching the wild-type sequence are used during ddPCR. The
      ratio of FAM/HEX-positive droplets is constant when wild-type amplicons are
      amplified but deviates when mutations anywhere under the FAM or HEX probes are
      present. To enhance the change in FAM/HEX ratio, we employed COLD-PCR cycling
      conditions that enrich mutation-containing amplicons anywhere on the sequence. We
      validated COLD-ddPCR on multiple mutations in TP53 and in EGFR using serial
      mutation dilutions and cell-free circulating DNA samples, and demonstrate
      detection down to approximately 0.2% to 1.2% mutation abundance. COLD-ddPCR
      enables a simple, rapid, and robust two-fluorophore detection method for the
      identification of multiple mutations during ddPCR and potentially can identify
      unknown DNA variants present in the target sequence. 

PMID- 25772707
TI  - A retrospective analysis of the activity and safety of oral Etoposide in heavily
      pretreated metastatic breast cancer patients.
AB  - Metastatic breast cancer (MBC) patients derive benefit from chemotherapy, but
      options become limited after several prior chemotherapeutic regimens. Oral
      etoposide (VP-16) has previously been found to be clinically active in MBC
      patients in phase II trials. However, with increasing availability of other
      drugs, etoposide use has declined in spite of its unfavorable toxicity profile
      probably being overestimated. We therefore evaluated the clinical benefit and
      safety of oral etoposide in a population of MBC patients who had failed multiple
      regimens of currently used therapies. Sixty-six patients with MBC previously
      treated with a median of eight (range 2-13) regimens of therapy were eligible for
      the study. Patients received 50 mg/day oral etoposide in 20-day cycles with 1
      week of rest. All patients were evaluated for clinical benefit (clinical benefit
      rate [CBR], complete response, partial response, and disease stabilization >24
      weeks), progression-free survival (PFS), overall survival (OS), and toxicities.
      Median PFS was 4 months, CBR was 18% (overall response rate 4%), and median OS
      from the start of treatment was 11 months. Little clinically significant or high
      grade toxicity were observed. No patients withdrew from treatment due to
      etoposide-induced toxicity. The favorable clinical response, low toxicity, and
      low cost of the drug suggest that etoposide is a viable option for patients with
      heavily pretreated MBC.

PMID- 25772708
TI  - Reflections on the extinction-explosion dichotomy.
AB  - A wide range of stochastic processes that model the growth and decline of
      populations exhibit a curious dichotomy: with certainty either the population
      goes extinct or its size tends to infinity. There is an elegant and classical
      theorem that explains why this dichotomy must hold under certain assumptions
      concerning the process. In this note, I explore how these assumptions might be
      relaxed further in order to obtain the same, or a similar conclusion, and obtain
      both positive and negative results. 

PMID- 25772709
TI  - Invasion and metastasis--recent advances and future challenges.

PMID- 25772711
TI  - The German Version of the Behavioral Activation for Depression Scale (BADS): A
      Psychometric and Clinical Investigation.
AB  - The Behavioral Activation for Depression Scale (BADS) was developed to measure
      core concepts of behavioural activation for depression. A number of studies,
      mostly based on analogue samples, have provided initial support for the BADS. In
      the present study, we examined the psychometric properties of the German version
      of the scale more broadly, including change sensitivity and clinical treatment
      data. A mixed sample of students (N = 312) and depressed outpatients in partial
      remission undergoing cognitive-behavioural group treatment for depressive
      rumination (N = 59) was examined. To analyze construct validity, a set of
      theoretically relevant constructs such as perseverative thinking, distraction and
      mindfulness was also assessed. Results indicated good psychometric properties,
      additional evidence for construct validity of the total scale and subscales, and
      adequate fit of the data to the original factor structure. Furthermore, the BADS
      proved to be sensitive to changes in participants undergoing treatment for
      depression. Copyright (c) 2015 John Wiley & Sons, Ltd. KEY PRACTITIONER MESSAGE:
      Behavioural activation (BA) is an effective treatment for patients suffering from
      unipolar depression. The Behavioral Activation for Depression Scale (BADS) can be
      used to measure core elements of the BA treatment rationale. It is useful to
      track changes in activation within treatment. The BADS is available in different
      languages and has shown to possess good psychometric properties.

PMID- 25772710
TI  - Hypoxia-inducible factors and hypertension: lessons from sleep apnea syndrome.
AB  - Systemic hypertension is one of the most prevalent cardiovascular diseases. Sleep
      disordered breathing (SDB) with recurrent apnea is a major risk factor for
      developing essential hypertension. Chronic intermittent hypoxia (CIH) is a
      hallmark manifestation of recurrent apnea. Rodent models patterned after the O2
      profiles seen with SDB patients showed that CIH is the major stimulus for causing
      systemic hypertension. This article reviews the physiological and molecular basis
      of CIH-induced hypertension. Physiological studies have identified that augmented
      carotid body chemosensory reflex and the resulting increase in sympathetic nerve
      activity are major contributors to CIH-induced hypertension. Analysis of
      molecular mechanisms revealed that CIH activates hypoxia-inducible factor (HIF)-1
      and suppresses HIF-2-mediated transcription. Dysregulation of HIF-1- and HIF-2
      mediated transcription leads to imbalance of pro-oxidant and anti-oxidant enzyme
      gene expression resulting in increased reactive oxygen species (ROS) generation
      in the chemosensory reflex which is central for developing hypertension. 

PMID- 25772712
TI  - The effect of CPAP treatment on EEG of OSAS patients.
AB  - PURPOSE: Continuous positive airway pressure (CPAP) is currently the most
      effective treatment method for obstructive sleep apnea syndrome (OSAS). The
      purpose of this study was to compare the sleep electroencephalogram (EEG) changes
      before and after the application of CPAP to OSAS patients. METHODS: A
      retrospective study was conducted and 45 sequential patients who received both
      polysomnography (PSG) and CPAP titration were included. The raw data of sleep EEG
      were extracted and analyzed by engineers using two main factors: fractal
      dimension (FD) and the zero-crossing rate of detrended FD (zDFD). FD was an
      effective indicator reflecting the EEG complexity and zDFD was useful to reflect
      the variability of the EEG complexity. The FD and zDFD indexes of sleep EEG of 45
      OSAS patients before and after CPAP titration were analyzed. RESULTS: The age of
      45 OSAS patients was 52.7 +/- 5.6 years old and the patients include 12 females
      and 33 males. After CPAP treatment, FD of EEG in non-rapid eye movement (NREM)
      sleep decreased significantly (P < 0.05), while FD of EEG increased in rapid eye
      movement (REM) sleep (P < 0.05). Meanwhile, zDFD were decreased remarkably in
      both NREM and REM sleep after CPAP therapy (P < 0.05, respectively). CONCLUSIONS:
      CPAP therapy had a significant influence on sleep EEG in patients with OSAHS,
      which lead to a more stable EEG pattern. This may be one of the mechanisms that
      CPAP could improve sleep quality and brain function of OSAS patients.

PMID- 25772713
TI  - Rethinking AASM guideline for split-night polysomnography in Asian patients with
      obstructive sleep apnea.
AB  - PURPOSE: Split-night polysomnography (SN-PSG) provides both a diagnosis and
      titration of continuous positive airway pressure over a single night in patients
      with suspected obstructive sleep apnea (OSA). However, in Asian patients, the
      diagnostic validity of American Academy of Sleep Medicine (AASM) guidelines for
      SN-PSG remains uncertain. Therefore, we examined whether the current criteria for
      SN-PSG are pertinent for Asian patients. METHOD: We investigated 134 consecutive
      patients who were diagnosed with OSA (apnea-hypopnea index (AHI) >= 5). We
      divided the raw data (full-night study) into two parts and compared the first 2 h
      of sleep with the full night of sleep to evaluate the diagnostic precision and
      accuracy of the first 2 h of sleep. RESULTS: No difference in AHI was observed
      between the first 2 h and the full night of sleep. A significant correlation of
      AHI was observed between the first 2 h and the full night of sleep for severe OSA
      patients (AHI >= 30). A correlation coefficient of AHI was higher by the
      criterion of AHI >= 30 than by the criterion of AHI >= 40 (r = 0.831 and r =
      0.778, respectively), which is the current AASM criterion for SN-PSG. Moreover,
      the criterion AHI >= 30 showed better diagnostic accuracy than the criterion AHI
      >= 40 (89.3 and 88.7 %, respectively). CONCLUSIONS: This study found possible
      evidence supporting different diagnostic criteria for SN-PSG in Asian population.
      We suggest further studies in other Asian populations to confirm these findings.

PMID- 25772719
TI  - Physical Medicine Interventions to Avoid Acute Respiratory Failure and Invasive
      Airway Tubes.
AB  - This article describes the use of physical medicine noninvasive inspiratory and
      expiratory muscle aids to prevent ventilatory/respiratory failure and to permit
      the extubation and tracheostomy tube decannulation of patients with little or no
      autonomous ability to breathe (ie, those who cannot be weaned from ventilator
      support). Noninvasive airway pressure aids can provide continuous ventilatory
      support and effective cough flows for patients with severely dysfunctional
      respiratory muscles. 

PMID- 25772718
TI  - The significance of serum uric acid level in humans with acute paraquat
      poisoning.
AB  - Hyperuricemia is a strong and independent predictor of all-cause mortality in
      cardiovascular disease and has been found to play a role in diseases exacerbated
      by oxidative stress and inflammation. This study aimed to evaluate whether serum
      uric acid (UA) level is an indicator of outcome in patients with acute paraquat
      poisoning. A total of 205 subjects who had attempted suicide by oral ingestion of
      paraquat were admitted to the emergency room between January 2009 and June 2014.
      Initial serum UA level and other laboratory parameters were measured. A total of
      66 patients died during the 30 days after admission, corresponding to a 32.2%
      cumulative incidence of mortality. UA levels were higher in non-survivors than
      survivors (P < 0.001) and 30-day mortality increased with increasing baseline
      serum UA level (P < 0.001). In a prediction analysis for 30-day mortality, the
      serum UA level had a cut-off concentration of 284 umol/L in female patients and
      352 umol/L in male patients. Multivariate Cox proportional hazards regression
      analyses showed that white blood cell counts and UA were independent prognostic
      factors. In conclusion, we showed that serum UA may be an independent predictor
      of 30-day mortality in patients with paraquat poisoning.

PMID- 25772720
TI  - Psychological Distress After Orthopedic Trauma: Prevalence in Patients and
      Implications for Rehabilitation.
AB  - Orthopedic trauma is an unforeseen life-changing event. Serious injuries include
      multiple fractures and amputation. Physical rehabilitation has traditionally
      focused on addressing functional deficits after traumatic injury, but important
      psychological factors also can dramatically affect acute and long-term recovery.
      This review presents the effects of orthopedic trauma on psychological distress,
      potential interventions for distress reduction after trauma, and implications for
      participation in rehabilitation. Survivors commonly experience post-traumatic
      stress syndrome, depression, and anxiety, all of which interfere with functional
      gains and quality of life. More than 50% of survivors have psychological distress
      that can last decades after the physical injury has been treated. Early
      identification of patients with distress can help care teams provide the
      resources and support to offset the distress. Several options that help trauma
      patients navigate their short-term recovery include holistic approaches, pastoral
      care, coping skills, mindfulness, peer visitation, and educational resources. The
      long-term physical and mental health of the trauma survivor can be enhanced by
      strategies that connect the survivor to a network of people with similar
      experiences or injuries, facilitate support groups, and social support networking
      (The Trauma Survivors Network). Rehabilitation specialists can help optimize
      patient outcomes and quality of life by participating in and advocating these
      strategies. 

PMID- 25772721
TI  - Perceived Quality of Life With Spinal Cord Injury: A Comparison Between Emergency
      Medicine and Physical Medicine and Rehabilitation Physicians.
AB  - OBJECTIVE: To explore the attitudes of health care providers who treat patients
      with spinal cord injury (SCI) and examine whether Emergency Medicine (EM) and
      Physical Medicine and Rehabilitation (PM&R) physicians differ in their judgments
      about quality of life (QOL) after SCI. DESIGN: Questionnaire survey of PM&R and
      EM physicians. PARTICIPANTS: Board-certified PM&R and EM physicians listed in the
      American Academy of Physical Medicine & Rehabilitation and the American College
      of Emergency Physicians and/or faculty from academic PM&R and EM departments in
      the United States and Canada. MAIN OUTCOME MEASUREMENTS: Evaluating various
      aspects of perceived QOL if the physician hypothetically sustained an SCI,
      including impact on leisure activities, social relationships, happiness,
      meaningful work, satisfying sexual relationships, and overall QOL. RESULTS: A
      total of 91 EM physicians and 89 PM&R physicians completed the surveys. PM&R
      physicians were more likely to agree that they would have a better QOL compared
      with EM physicians, regardless of the level of injury or aspect of life (P < .01
      in all cases). Female physicians, regardless of specialty, were more likely to
      choose a lower level at which they would choose to die, rather than live, if they
      sustained an SCI (P = .03). Physicians in both groups were more likely to
      disagree that they would have a high QOL at a lower level of injury if they
      disagreed at a higher level of injury (P <= .02). CONCLUSIONS: Regardless of
      specialty, PM&R and EM physicians have their own personal perceptions of QOL with
      SCI. PM&R physicians tend to believe that they would have a higher QOL with an
      SCI compared with EM physicians and likely have a more optimistic view of SCI.
      Patient care may be improved by interdisciplinary discussion, as evidenced by the
      disparity exhibited by practitioners in these 2 specialties who care for the same
      patient population.

PMID- 25772722
TI  - Lateral Antebrachial Cutaneous Nerve Entrapment After Shoulder Arthroscopy: A
      Case Report.
AB  - The lateral antebrachial cutaneous nerve (LABCN) is a distal sensory branch of
      the musculocutaneous nerve that innervates the radial aspect of the forearm.
      Cases of LABCN injury from trauma and chronic compression have been reported. A
      case of musculocutaneous nerve injury after a biceps tenodesis has also been
      reported. This case report describes an LABCN injury and forearm pain after a
      biceps tenodesis procedure. Using a multifaceted diagnostic approach of
      electrodiagnostics and magnetic resonance neurography, the site of compression
      was appropriately localized. The patient ultimately achieved relief after a
      surgical decompression. 

PMID- 25772723
TI  - Variability of the Ischiofemoral Space Relative to Femur Position: An Ultrasound
      Study.
AB  - BACKGROUND: Ischiofemoral impingement is caused by compression of the quadratus
      femoris muscle between the ischial tuberosity and lesser trochanter. The
      evaluation of ischiofemoral impingement includes radiologic studies to evaluate
      the ischiofemoral space dimensions. No prior study has evaluated the effect of
      femoral position on ischiofemoral space dimensions. OBJECTIVE: To determine
      whether the dimensions of the ischiofemoral space vary with changes in femoral
      position. DESIGN: Cross-sectional study. SETTING: Academic institution.
      PARTICIPANTS: Six male and four female subjects with no hip pain and no history
      of hip disorders or surgery were selected to participate in the study. The
      subjects' mean age was 31.5 years; mean height, 176.8 cm; mean weight, 70.2 kg;
      and mean body mass index, 23.6 kg/m(2). METHODS: Ultrasound was used to measure
      the ischiofemoral space in bilateral gluteal regions of each volunteer. The
      volunteers underwent imaging in a prone position. The ischiofemoral space was
      measured with the femur in 9 different positions created through various
      combinations of frontal (15 degrees  abduction, neutral, and 15 degrees 
      adduction) and transverse (30 degrees  internal rotation, neutral, and 30 degrees
      external rotation) plane hip motions. MAIN OUTCOME MEASUREMENTS: The narrowest
      ischiofemoral interval, defined as the narrowest distance between the medial
      cortex of the lesser trochanter and the lateral cortex of the ischial tuberosity.
      RESULTS: The anatomic landmarks used to measure the ischiofemoral space were
      easily identified in all subjects. The frontal plane main effect (F2,18 = 38.611)
      was statistically significant (P < .001), as was the transverse plane main effect
      (F2,18 = 82.452, P < .001). These findings indicated that there was a
      statistically significant difference in ischiofemoral space according to hip
      position in the frontal and transverse planes. The largest ischiofemoral space
      measurement occurred with the hip in abduction and internal rotation (51.8 mm;
      95% confidence interval [CI], 49.2-54.5 mm), whereas hip adduction and external
      rotation resulted in the narrowest ischiofemoral space measurement (30.8 mm; 95%
      CI, 25.5-36.0 mm). The largest difference was between the adduction-external
      rotation and the abduction-internal rotation positions (mean difference = 21.1
      mm; 95% CI, 13.7-28.5 mm; P < .001), and the smallest difference was between the
      adducted-neutral rotation and the abducted-external rotation positions (mean
      difference = 0.23 mm; 95% CI, -8.07-8.55 mm; P = .99). CONCLUSIONS: Femoral
      position affects ischiofemoral space dimensions. The ischiofemoral space widens
      with abduction and internal rotation and narrows with adduction and external
      rotation, and thus femoral position should be considered when imaging and
      measuring the ischiofemoral space.

PMID- 25772724
TI  - Antisaccades and executive dysfunction in PD: Two sides of the same coin?

PMID- 25772725
TI  - On the mechanism of catalytic hydrogenation of thiophene on hydrogen tungsten
      bronze.
AB  - Hydrogenation of unsaturated organosulfur compounds is an essential process
      through which these species are converted into cleaner and more useful compounds.
      Hydrogen bronze materials have been demonstrated to be efficient catalysts in
      hydrogenation of simple unsaturated compounds. Herein, we performed density
      functional theory calculations to investigate hydrogenation of thiophene on
      hydrogen tungsten bronze. Various reaction pathways were investigated and the
      most favourable routes were identified. Our results suggest that the reaction
      proceeds with moderate barriers, and formation of tetrahydrothiophene is facile
      both thermochemically and kinetically. The present study provides a useful
      insight into the design of hydrogenation thiophene and its derivatives and
      effective hydrodesulfurization catalysts. 

PMID- 25772726
TI  - Patient and family perspectives on respect and dignity in the intensive care
      unit.
AB  - Respect and dignity are central to moral life, and have a particular importance
      in health care settings such as the intensive care unit (ICU). We conducted 15
      semistructured interviews with 21 participants during an ICU admission to explore
      the definition of, and specific behaviors that demonstrate, respect and dignity
      during treatment in the ICU. We transcribed interviews and conducted thematic
      qualitative analysis. Seven themes emerged that focused on what it means to be
      treated with respect and/or dignity: treated as a person; Golden Rule;
      acknowledgement; treated as family/friend; treated as an individual; treated as
      important/valuable; and treated as equal. Participants described particular
      behaviors or actions that were considered related to demonstrating treatment with
      respect and dignity: listening; honesty/giving information; attention to
      body/modesty/appearance; caring/bedside manner; patient and family as an
      information source; attention to pain; and responsiveness. These behaviors
      provide a framework for improving experiences with care in the ICU. 

PMID- 25772727
TI  - Toward treatment with respect and dignity in the intensive care unit.
AB  - Despite concern that patients in the intensive care unit (ICU) may not be treated
      with respect and dignity, there is not conceptual clarity regarding what
      constitutes such treatment. In addition, measures specific to treatment with
      respect and dignity in the ICU are unavailable. Accordingly, a multidisciplinary
      group developed a conceptual model for treatment with respect and dignity in the
      ICU and used mixed methods to gather data on this issue. This effort included
      interviews with patients and families, focus groups with health care
      professionals, and direct observations. These data were then compared and
      contrasted to synthesize what was learned. Finally, pilot quantitative patient
      and family survey data were collected and analyzed. Each of these approaches,
      which comprise the papers in this supplement to Narrative Inquiry in Bioethics,
      is briefly described in this article.

PMID- 25772728
TI  - Health care professionals' perceptions and experiences of respect and dignity in
      the intensive care unit.
AB  - Little is known about health care professionals' perceptions regarding what it
      means to treat patients and families with respect and dignity in the intensive
      care unit (ICU) setting. To address this gap, we conducted nine focus groups with
      different types of health care professionals (attending physicians,
      residents/fellows, nurses, social workers, pastoral care, etc.) working in either
      a medical or surgical ICU within the same academic health system. We identified
      three major thematic domains, namely, intrapersonal (attitudes and beliefs),
      interpersonal (behaviors), and system (contextual) factors that influence
      treatment with respect and dignity. Participants suggested strategies for
      improving treatment of patients and families in the ICU with respect and dignity,
      as well as the related need for enhancing respect among the multidisciplinary
      team of clinicians. Implementing these strategies will require innovative
      educational interventions and leadership. Future research should focus on the
      design and evaluation of such interventions on the quality of care.

PMID- 25772729
TI  - Observations of respect and dignity in the intensive care unit.
AB  - Treating patients and their family members with respect and dignity is a broadly
      accepted goal of health care. The work presented in this article is part of a
      larger project aimed at better understanding what constitutes treatment with
      respect and dignity in the ICU to improve the care that patients and family
      members receive in this regard. Direct observation was selected as one of the
      methods to facilitate this understanding because it provides the opportunity to
      see and document what actually occurs during encounters among patients, their
      families, and clinicians. This article reports seven major thematic domains and
      many subthemes that together create a detailed account of the interpersonal and
      environmental components of treatment with respect and dignity. Attention to
      these components might enhance the experience and treatment of patients and
      family members. 

PMID- 25772730
TI  - Understanding treatment with respect and dignity in the intensive care unit.
AB  - Despite wide recognition of the importance of treating patients with respect and
      dignity, little is known about what constitutes treatment in this regard. The
      intensive care unit (ICU) is a unique setting that can pose specific threats to
      treatment with respect and dignity owing to the critical state of patients,
      stress and anxiety amongst patients and their family members, and the highly
      technical nature of the environment. In attempt to understand various
      stakeholders' perspectives of treatment with respect and dignity, patients and
      family members were interviewed, a wide range of health care professionals
      participated in focus groups, and third party observers took field notes of
      interactions in the ICU. This paper compares and contrasts the data that were
      generated using these different methods. Triangulating the data in this way
      contributes to a more complete and nuanced understanding of treatment with
      respect and dignity in the ICU. 

PMID- 25772731
TI  - Respect and dignity: a conceptual model for patients in the intensive care unit.
AB  - Although the concept of dignity is commonly invoked in clinical care, there is
      not widespread agreement--in either the academic literature or in everyday
      clinical conversations--about what dignity means. Without a framework for
      understanding dignity, it is difficult to determine what threatens patients'
      dignity and, conversely, how to honor commitments to protect and promote it. This
      article aims to change that by offering the first conceptual model of dignity for
      patients in the intensive care unit. The conceptual model we present is based on
      the notion that there are three sources of patients' dignity-their shared
      humanity, personal narratives, and autonomy-each of which independently warrants
      respect. The article describes each source of dignity and draws on examples to
      illustrate how clinician attitudes, actions, and behaviors can either contribute
      to, or detract from, expressions of respect for patient dignity.

PMID- 25772732
TI  - Measuring patients' experiences of respect and dignity in the intensive care
      unit: a pilot study.
AB  - In this study, we tested the feasibility of conducting quantitative assessments
      of patients' experiences with care in the intensive care unit (ICU), in regard to
      treatment with respect and dignity. Patients completed the Patient Dignity
      Inventory, Collaborate, and selected domains from the Hospital Consumer
      Assessment of Health Providers and Systems Survey. Family members were
      additionally surveyed using the Family Satisfaction in ICU Care questionnaire.
      Overall, patients reported high levels of satisfaction in terms of nurses and
      doctors treating them with courtesy and respect; however, physical aspects of
      care were reported to be more problematic. While this pilot study suggests some
      target areas for improving treatment with respect and dignity, the findings are
      limited since many patients were unable to participate in the survey. Future work
      should be directed at developing new measures that are easier to administer in
      this setting. 

PMID- 25772733
TI  - Editors' note.

PMID- 25772734
TI  - Sweet syndrome caused by oral contraceptives.

PMID- 25772735
TI  - The use of large healthcare data sets in pursuit of a clinical question.
AB  - The use of large healthcare databases may be of interest to nurse practitioners
      who wish to answer clinical questions. This column will provide information about
      access to selected large healthcare databases, requirements for statistical
      software, and the skills required to utilize these databases. 

PMID- 25772736
TI  - Inhibition of human alcohol and aldehyde dehydrogenases by aspirin and
      salicylate: assessment of the effects on first-pass metabolism of ethanol.
AB  - Previous studies have reported that aspirin significantly reduced the first-pass
      metabolism (FPM) of ethanol in humans thereby increasing adverse effects of
      alcohol. The underlying causes, however, remain poorly understood. Alcohol
      dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH), principal enzymes
      responsible for metabolism of ethanol, are complex enzyme families that exhibit
      functional polymorphisms among ethnic groups and distinct tissue distributions.
      We investigated the inhibition profiles by aspirin and its major metabolite
      salicylate of ethanol oxidation by recombinant human ADH1A, ADH1B1, ADH1B2,
      ADH1B3, ADH1C1, ADH1C2, ADH2, and ADH4, and acetaldehyde oxidation by ALDH1A1 and
      ALDH2, at pH 7.5 and 0.5 mM NAD(+). Competitive inhibition pattern was found to
      be a predominant type among the ADHs and ALDHs studied, although noncompetitive
      and uncompetitive inhibitions were also detected in a few cases. The inhibition
      constants of salicylate for the ADHs and ALDHs were considerably lower than that
      of aspirin with the exception of ADH1A that can be ascribed to a substitution of
      Ala-93 at the bottom of substrate pocket as revealed by molecular docking
      experiments. Kinetic inhibition equation-based simulations show at higher
      therapeutic levels of blood plasma salicylate (1.5 mM) that the decrease of
      activities at 2-10 mM ethanol for ADH1A/ADH2 and ADH1B2/ADH1B3 are predicted to
      be 75-86% and 31-52%, respectively, and that the activity decline for ALDH1A1 and
      ALDH2 at 10-50 MUM acetaldehyde to be 62-73%. Our findings suggest that
      salicylate may substantially inhibit hepatic FPM of alcohol at both the ADH and
      ALDH steps when concurrent intaking aspirin.

PMID- 25772737
TI  - The native structure of annexin A2 peptides in hydrophilic environment determines
      their anti-angiogenic effects.
AB  - The progression of aggressive cancer occurs via angiogenesis and metastasis makes
      these processes important targets for the development of anti-cancer agents.
      However, recent studies have raised the concern that selective inhibition of
      angiogenesis results in a switch towards increased tumour growth and metastasis.
      Since Annexin A2 (AnxA2) is involved in both angiogenesis and metastasis, it may
      serve as an ideal target for the simultaneous inhibition of both processes. Based
      on the discovery that domains I (D(I)) and IV (D(IV)) of AnxA2 are potent
      inhibitors of angiogenesis, we designed seven peptides derived from these domains
      based on AnxA2 crystal structures. The peptides were expressed as fusion peptides
      to increase their folding and solubility. Light scattering, far-UV circular
      dichroism and thermal transition analyses were employed to investigate their
      aggregation tendencies, alpha-helical propensity and stability, respectively.
      2,2,2-trifluoroethanol (50%) increased the alpha-helical propensities of all
      peptides, indicating that they may favour a hydrophobic environment, but did not
      enhance their thermal stability. D(I)-P2 appears to be the most stable and folded
      peptide in a hydrophilic environment. The secondary structure of D(I)-P2 was
      confirmed by nuclear magnetic resonance spectra. The effect of the seven AnxA2
      peptides on the formation and integrity of capillary-like networks was studied in
      a co-culture system mimicking many of the angiogenesis-related processes.
      Notably, D(I)-P2 inhibited significantly network formation in this system,
      indicating that the folded D(I)-P2 peptide interferes with vascular endothelial
      growth factor-dependent pro-angiogenic processes. Thus, this peptide has the
      potential of being developed further as an anti-angiogenic drug.

PMID- 25772738
TI  - Outcomes of patients implanted with a left ventricular assist device at
      nontransplant mechanical circulatory support centers.
AB  - The goal of this study was to assess outcomes of patients who underwent
      implantation of left ventricular assist devices (LVADs) at nontransplantation
      mechanical circulatory support centers. As the availability of LVADs for advanced
      heart failure has expanded to nontransplantation mechanical circulatory support
      centers, concerns have been expressed about maintaining good outcomes.
      Demographics and outcomes were evaluated in 276 patients with advanced heart
      failure who underwent implantation of LVADs as bridge to transplantation or
      destination therapy at 27 open-heart centers. Baseline characteristics, operative
      mortality, length of stay, readmission rate, adverse events, quality of life, and
      survival were analyzed. The overall 30-day mortality was 3% (8 of 276), and
      survival rates at 6, 12, and 24 months, respectively, were 92+/-2%, 88+/-3%, and
      84+/-4% for the bridge-to-transplantation group and 81+/-3%, 70+/-5%, and 63+/-6%
      for the destination therapy group, comparable with results published by the
      national Interagency Registry for Mechanically Assisted Circulatory Support
      (INTERMACS). The median length of stay for all patients was 21 days. Bleeding was
      the most frequent adverse event. Stroke occurred in 4% (bridge to
      transplantation) and 6% (destination therapy) of patients. Quality-of-life
      measures and 6-minute walk distances showed sustained improvements throughout
      support. In conclusion, outcomes with LVAD support at open-heart centers are
      acceptable and comparable with results from the INTERMACS registry. With
      appropriate teams, training, center commitment, and certification, LVAD therapy
      is being disseminated in a responsible way to open-heart centers.

PMID- 25772739
TI  - Prognostic value of the age, creatinine, and ejection fraction score for 1-year
      mortality in 30-day survivors who underwent percutaneous coronary intervention
      after acute myocardial infarction.
AB  - Few simple and effective tools are available for determining the prognosis of 30
      day survivors after acute myocardial infarction. We aimed to assess whether the
      simple age, creatinine, and ejection fraction (ACEF) score could predict 1-year
      mortality of 12,000 post-myocardial infarction 30-day survivors who underwent
      percutaneous coronary intervention. The ACEF score was computed as follows:
      (age/ejection fraction)+1, if the serum creatinine was >2 mg/dl. Accuracy was
      defined through receiver-operating characteristics analysis and area under the
      curve (AUC) evaluation. Twelve risk factors were selected and ranked according to
      their AUC value. Age, ejection fraction, and serum creatinine levels indicated
      the best AUC value. The ACEF score was significantly higher in the nonsurvivors
      (1.95+/-0.82 vs 1.28+/-0.50; p<0.001) and was an independent predictor of 1-year
      mortality (adjusted hazard ratio 2.26; p<0.001). The best accuracy was achieved
      by a prediction model including 12 risk factors (AUC=0.80), but this did not
      significantly differ compared with the AUC (0.79) of the ACEF score (p=ns).
      Adjusted hazard ratios for 1-year mortality were 1 (reference), 3.11 (p<0.001),
      and 10.38 (p<0.001) for the ACEFLOW (ACEF score<1.0), ACEFMID (ACEF score 1.0 to
      1.39), and ACEFHIGH (ACEF score>=1.4) groups, respectively. The ACEF score may be
      a novel valid model to stratify the 1-year mortality risk in 30-day survivors who
      underwent percutaneous coronary intervention after acute myocardial infarction.

PMID- 25772740
TI  - Meta-analysis of the relation of body mass index to all-cause and cardiovascular
      mortality and hospitalization in patients with chronic heart failure.
AB  - Clinical studies have indicated the existence of an "obesity paradox" in patients
      with chronic heart failure (HF), that is, reduced mortality in patients who have
      elevated body mass index (BMI) scores compared with normal-weight reference
      groups. The aim of this study was to investigate the relation of BMI with all
      cause and cardiovascular (CV) mortality and hospitalization in patients with
      chronic HF though a systematic review and meta-analysis of published research.
      PubMed, the Cumulative Index to Nursing and Allied Health Literature, Cochrane
      Central, Scopus, web of science and Embase were searched for studies reporting
      rates of total mortality, cardiac mortality, and risk for hospitalization in
      patients with HF in various BMI categories (<20 kg/m(2) [low], 20 to 24.9 kg/m(2)
      [normal reference], 25 to 29.9 kg/m(2) [overweight], 30 to 34.9 [obese], and >=35
      kg/m(2) [severely obese]). Event rates were compared using a forest plot of
      relative risk (RR) using a random-effects model assuming interstudy
      heterogeneity. Two study investigators independently reviewed the 124 reports
      retrieved and identified 6 for final analyses (n = 22,807). After a mean follow
      up period of 2.85 years, the risk for adverse events was highest in patients with
      low BMIs: total mortality RR 1.27 (95% confidence interval [CI] 1.17 to 1.37), CV
      mortality RR 1.20 (95% CI 1.01 to 1.43), and hospitalization RR 1.19 (95% CI 1.09
      to 1.30). Risk for CV mortality and hospitalization was lowest in overweight
      patients (RR 0.79, 95% CI 0.70 to 0.90, and RR 0.92, 95% CI 0.86 to 0.97,
      respectively). Increasing degree of obesity failed to achieve a statistically
      significant effect on CV mortality (RR 0.82, 95% CI 0.64 to 1.05, and RR 0.71,
      95% CI 0.50 to 1.01, for obese and severely obese, respectively) and on
      hospitalization (RR 0.99, 95% CI 0.92 to 1.07, and RR 1.28, 95% CI 0.88 to 1.87,
      for obese and severely obese, respectively). In conclusion, risk for total
      mortality and CV mortality and hospitalization was highest in patients with
      chronic HF who were underweight as defined by low BMI, whereas risk for CV
      mortality and hospitalization was lowest in overweight subjects.

PMID- 25772741
TI  - Natural history of cardiac arrest in patients with takotsubo cardiomyopathy.
AB  - Cardiac arrest (CA) is relatively rare but lethal complication of takotsubo
      cardiomyopathy (TTC). In most instances, patients are diagnosed with TTC after
      CA, making it difficult to distinguish if TTC is the precipitant or the
      consequence of the index event. In this systematic review, patient-level data
      were obtained to seek out the characteristics of patients in whom the underlying
      cause of CA is TTC. A comprehensive search of 4 major databases (Embase, Ovid
      MEDLINE, PubMed, and Google Scholar) was performed from their inception to the
      last week of September 2014. Of 186 citations, 62 case studies were included in
      the analysis, providing patient-level data on 77 patients. In 60 patients (78%),
      the diagnosis of TTC was made after CA. Patients presenting with CA were younger
      (mean age 49.5 +/- 16 vs 64.9 +/- 11 years, p <0.0001) and had relatively shorter
      corrected QT interval (mean 530 +/- 101 vs 616 +/- 140 ms) on
      electrocardiography. TTC-related hypotension was the major cause of CA in the
      acute phase, while a long corrected QT interval triggered CA in the subacute (24-
      to 72-hour) phase. In 11 patients, CA was not directly instigated by TTC despite
      a left ventricular appearance matching TTC. In conclusion, in TTC, CA typically
      develops within the first 3 days of presentation and is the result of long
      corrected QT interval-induced polymorphic ventricular tachycardia. Secondary TTC,
      in which patients present with typical left ventricular features after CA, likely
      represents a distinct cohort in which identifiable inheritable arrhythmias or
      structural heart disease should be sought.

PMID- 25772742
TI  - Comparison of Strut Coverage at 6 Months by Optical Coherence Tomography With
      Everolimus-Eluting Stenting of Bare-Metal Stent Restenosis Versus Stenosis of
      Nonstented Atherosclerotic Narrowing (from the DESERT Study).
AB  - Incomplete struts coverage is a predictor of late stent thrombosis after
      implantation of the drug-eluting stents (DES) in atherosclerotic lesions. The
      process of struts coverage in DES implanted for bare-metal stent (BMS) restenosis
      has never been described. Thirty-two patients with stable coronary artery disease
      were consecutively selected, 11 with BMS restenosis (group A) and 21 with de novo
      atherosclerotic lesions (group B). All patients underwent everolimus-eluting
      stent implantation; coronary angiography and optical coherence tomography were
      performed at 6 months follow-up. Percentage difference in struts coverage between
      the 2 groups was the primary end point. A total of 85,773 struts (17,891 in group
      A and 67,882 in group B) were analyzed: compared with group B, the percentage of
      uncovered stent struts was significantly lower in group A (2.6% vs 4.8%; p
      <0.0001). In group A, DES struts protruding out of BMS were more uncovered (5.0%
      vs 1.9%; p <0.0001) and malapposed (4.1% vs 2.1%; p <0.0001) compared with
      overlapping struts. In conclusion, when DES are implanted to treat BMS
      restenosis, struts coverage at 6 months follow-up is more complete compared with
      DES implanted in atherosclerotic lesions.

PMID- 25772743
TI  - Controlled trial of an Internet-based intervention for overweight teens
      (Next.Step): effectiveness analysis.
AB  - Adolescent obesity is a major health problem. The need for effective adolescent
      weight management programs is of high clinical and public health relevance. This
      study evaluates the effectiveness of an e-therapeutic platform (Next.Step),
      aiming to promote weight management skills and the adoption of health-promoting
      lifestyles. This nonrandomized clinical trial with control group uses a sample of
      94 adolescents who attended a paediatric obesity clinic. The experimental group
      was invited to access the platform Next.Step during 24 weeks, in addition to the
      standard treatment program. The control group followed the standard treatment
      protocol and joined a waiting list. Overall, the outcomes of the e-therapeutic
      program were not substantially better than those obtained with a traditional kind
      of intervention despite the intervention being associated with an improved health
      responsibility score (d = 0.51; p = 0.014). Several predictors of the Next.Step
      effectiveness were found. CONCLUSION: Although the e-therapeutic program led to a
      significant increase in health responsibility, inconclusive results were found
      regarding the program effectiveness compared to the standard multidisciplinary
      intervention. The lack of significant differences between groups may be due to
      the reduced rates of program adherence and the high dropout rate. WHAT IS KNOWN:
      * Adolescent obesity has reached epidemic proportions, and standard treatment
      programs have been unable to achieve the desired adherence so far. * Internet
      based programs have already shown positive results in the adult obese population,
      but information is scarce regarding adolescents. WHAT IS NEW: * This study
      assesses the effectiveness of a structured case management program including
      communication technologies on both the behavioural change and the health of obese
      adolescents. * The e-therapeutic program led to an increase in health
      responsibility.

PMID- 25772744
TI  - Early detection of hymenal anomalies and variants.

PMID- 25772745
TI  - Measuring Prices in Health Care Markets Using Commercial Claims Data.
AB  - OBJECTIVE: To compare methods of price measurement in health care markets. DATA
      SOURCES: Truven Health Analytics MarketScan commercial claims. STUDY DESIGN: We
      constructed medical prices indices using three approaches: (1) a "sentinel"
      service approach based on a single common service in a specific clinical domain,
      (2) a market basket approach, and (3) a spending decomposition approach. We
      constructed indices at the Metropolitan Statistical Area level and estimated
      correlations between and within them. PRINCIPAL FINDINGS: Price indices using a
      spending decomposition approach were strongly and positively correlated with
      indices constructed from broad market baskets of common services (r > 0.95).
      Prices of single common services exhibited weak to moderate correlations with
      each other and other measures. CONCLUSIONS: Market-level price measures that
      reflect broad sets of services are likely to rank markets similarly. Price
      indices relying on individual sentinel services may be more appropriate for
      examining specialty- or service-specific drivers of prices.

PMID- 25772746
TI  - A systematic review on definitions and assessments of psychotic-like experiences.
AB  - AIMS: Psychotic-like experiences (PLEs) or subclinical psychotic experiences have
      received increased attention as some studies have suggested continuity between
      PLEs and psychotic disorders. However, epidemiological and correlational studies
      of PLEs showed mixed findings - it is observed that different studies use a wide
      variety of definitions of PLEs, as well as different assessment tools that are
      designed to capture such described experiences. The differences in definitions
      and assessment tools adopted could contribute to the discrepancy of findings. The
      current review aims to examine the definitions and assessment tools adopted in
      the studies of PLEs. METHODS: Literature search was conducted between October
      2013 and February 2014 using three search engines: Medline, Web of Science and
      PubMed. RESULTS: A total of 76 papers met the selection criteria and were
      included in the current review. It is found that the majority of papers reviewed
      defined PLEs quantitatively using assessment tools and do not have a specific
      phenomenological definition, whereas assessment tools adopted have a wide
      variety. Furthermore, phenomenological studies of PLEs were rare. CONCLUSIONS:
      The variations in definitions and assessment tools of PLEs might contribute to
      mixed findings in researches. Reaching to a consensus through the study of
      phenomenology of PLEs is essential to further advancement of the research in this
      area.

PMID- 25772747
TI  - A chemical chaperone-based drug candidate is effective in a mouse model of
      amyotrophic lateral sclerosis (ALS).
AB  - Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease
      characterized by the selective death of motor neurons and skeletal muscle
      atrophy. The majority of ALS cases are acquired spontaneously, with inherited
      disease accounting for only 10 % of all cases. Recent studies provide compelling
      evidence that aggregates of misfolded proteins underlie both types of ALS. Small
      molecules such as artificial chaperones can prevent or even reverse the
      aggregation of proteins associated with various human diseases. However, their
      very high active concentration (micromolar range) severely limits their utility
      as drugs. We synthesized several ester and amide derivatives of chemical
      chaperones. The lead compound 14, 3-((5-((4,6-dimethylpyridin-2-yl)methoxy)-5
      oxopentanoyl)oxy)-N,N-dimethylpropan-1-amine oxide shows, in the micromolar
      concentration range, both neuronal and astrocyte protective effects in vitro; at
      daily doses of 10 mg kg(-1) 14 improved the neurological functions and delayed
      body weight loss in ALS mice. Members of this new chemical chaperone derivative
      class are strong candidates for the development of new drugs for ALS patients. 

PMID- 25772748
TI  - Macrophage activation marker soluble CD163 and non-alcoholic fatty liver disease
      in morbidly obese patients undergoing bariatric surgery.
AB  - BACKGROUND AND AIMS: Macrophages play an important role in non-alcoholic fatty
      liver disease (NAFLD). Soluble CD163 (sCD163) is a specific marker of macrophage
      activation. We aimed to measure sCD163 in morbidly obese patients with varying
      degrees of NAFLD before and after bariatric surgery (BS). METHODS: Demographic,
      clinical, and biochemical data, and plasma sCD163 measured by enzyme-linked
      immunosorbent assay, of 196 patients were collected preoperatively and 3, 6, and
      12 months after BS leading to significant weight loss. Peroperative liver
      biopsies were assessed for the NAFLD Activity Score (NAS), Kleiner fibrosis
      score, and the fatty liver inhibition of progression (FLIP) algorithm. In a
      subset, CD163 immunohistochemistry and real-time quantitative polymerase chain
      reaction for CD163 mRNA were performed. RESULTS: sCD163 was higher in patients
      with NAS >= 5 compared with those with NAS < 5 (2.4(2.0-3.1) vs 1.9(1.5-2.3)
      mg/L, P < 0.001) and in patients with bridging fibrosis (F >= 3) compared with
      lower fibrosis stages (2.6(2.0-4.9) vs 2.0(1.5-2.4) mg/L, P = 0.001).
      Preoperative sCD163 was independently associated with both the NAS (P = 0.002)
      and the fibrosis score (P = 0.024). sCD163 decreased after BS and was greatly
      reduced after 12 months, more rapidly so in patients with NAS >= 5 (P < 0.001)
      and non-alcoholic steatohepatitis (NASH) according to the FLIP algorithm (P =
      0.03). Immunohistochemistry showed CD163-positive macrophages aligning fat-laden
      hepatocytes and forming microgranulomas in patients with NASH. CD163 mRNA
      expression did not vary with NAS. CONCLUSION: sCD163 increased in parallel with
      the severity of NAFLD in morbid obesity, indicating macrophage activation. BS
      reduced sCD163 even in patients with severe liver injury and fibrosis, suggesting
      full reversibility of macrophage activation associated with improved insulin
      sensitivity.

PMID- 25772749
TI  - Association of hair dye use with circulating levels of sex hormones in
      premenopausal Japanese women.
AB  - BACKGROUND: Substances identified as animal carcinogens are no longer used as
      ingredients of hair dyes. However, hair dyes are diverse groups of chemicals, and
      certain compounds may affect endogenous sex hormone levels. We examined the
      association between hair dye use and sex hormone levels among premenopausal
      women. METHODS: Study subjects were 431 premenopausal Japanese women who had
      regular menstrual cycles less than 40 days long. Information on the use of hair
      dyes or hair bleach, the type of hair coloring used, the duration of use and the
      frequency of application was collected using a self-administered questionnaire.
      Fasting plasma samples were obtained to measure estradiol, testosterone,
      dehydroepiandrosterone sulfate, sex hormone-binding globulin, follicle
      stimulating hormone and luteinizing hormone. RESULTS: After controlling for
      covariates, the mean plasma total testosterone level was about 14% higher in
      women who had used hair dyes for 10 or more years than that among women who had
      never used them (P for trend = 0.02). A similar association was observed when the
      type of hair dye was restricted to permanent hair dyes. A higher frequency of
      applying non-permanent hair dyes was marginally significantly associated with
      higher total and free estradiol levels. CONCLUSIONS: Data suggest that long-term
      use of hair dyes may be associated with an increase in circulating testosterone
      levels. As this is, to our knowledge, the first study examining the association
      between hair dye use and sex hormone levels, replication of the results is
      required.

PMID- 25772750
TI  - The impact of 3D and 2D TV watching on neurophysiological responses and cognitive
      functioning in adults.
AB  - BACKGROUND: Watching three-dimensional television (3D TV) may strain the eyes.
      However, other potential harmful effects of 3D TV watching have been rarely
      investigated. The current study examined the impact of 3D TV watching on
      neurophysiological responses and cognitive functioning as compared with two
      dimensional TV (2D TV) watching. METHODS: A total of 72 individuals were randomly
      assigned to either a 3D TV watching group or a 2D TV watching group.
      Electroencephalography (EEG) was used to measure neurophysiological responses,
      and computerized neurocognitive tests were conducted immediately before and after
      TV watching. The Simulator Sickness Questionnaire (SSQ) was used to assess visual
      discomfort. RESULTS: There was a significant change in visual discomfort between
      the two groups (SSQ score at baseline: 2.28 +/- 3.05 for the 3D TV group and 3.69
      +/- 3.49 for the 2D TV group; SSQ score after watching TV: 4.6 +/- 3.35 for the
      3D TV group and 4.03 +/- 3.47 for the 2D TV group), and this change was greater
      for the 3D TV watching group (P = 0.025). However, 3D TV watching did not have a
      differential impact on EEG responses. Furthermore, there were no significant
      differences between the groups in terms of changes in cognitive performance,
      except for a subtle difference in backward digit span performance. CONCLUSION:
      Our findings suggest that 3D TV watching is as safe as 2D TV watching in terms of
      neurophysiological responses and cognitive functioning. Potential harmful effects
      of TV viewing might be similar regardless of whether 3D or 2D TV is viewed.

PMID- 25772751
TI  - Youth unemployment and functional somatic symptoms in adulthood: results from the
      Northern Swedish cohort.
AB  - BACKGROUND: Little is known about the possible long-term health consequences of
      youth unemployment. Research indicates that unemployment may lead to
      socioeconomic downward mobility and mental health problems, but we still lack
      knowledge of the long-term health consequences of youth unemployment. This
      article examines the potential long-term association between youth unemployment
      and functional somatic symptoms in adulthood. METHODS: The 'Northern Swedish
      cohort' was used with data from five data collections, from 1981 (age 16) until
      2007 (age 42). Youth unemployment was measured as months in unemployment between
      age 16 and 21, and health outcome as functional somatic symptoms (an index of 10
      items of self-reported symptoms). Linear regression was used to analyse the
      relationship between months in youth unemployment and functional somatic symptoms
      at age 21 and age 42, stratified for women and men and adjusted for potential
      confounders, such as time spent in education at age 21 and later unemployment
      between age 21 and 42. RESULTS: Youth unemployment was significantly related to
      functional somatic symptoms at age 21 for men after controlling for confounders,
      but not for women. Among men, the association remained for functional somatic
      symptoms at age 42, after controlling for confounders. CONCLUSIONS: Adolescence
      seems to be a sensitive period during which unemployment could have remaining
      health effects in adulthood, at least for men, though assumptions of causality
      are tentative and more research is needed.

PMID- 25772752
TI  - Access to healthcare for undocumented migrants with communicable diseases in
      Germany: a quantitative study.
AB  - BACKGROUND: Migrants without residence permits are de facto excluded from access
      to healthcare in Germany. There is one exception in relevant legislation: in the
      case of sexually transmitted infections and tuberculosis, the legislator has
      instructed the local Public Health Authorities to offer free and anonymous
      counseling, testing and, if necessary, treatment in case of apparent need.
      Furthermore, recommended vaccinations may be carried out free of charge. This
      study intends to comprehensively capture the services for undocumented migrants
      at Public Health Authorities in Germany. METHODS: An e-mail survey of all Local
      Public Health Authorities (n = 384) in Germany was carried out between January
      and March 2011 using a standardized questionnaire. RESULTS: One hundred thirty
      nine of 384 targeted local Health Authorities completed the questionnaire
      (36.2%), of which approximately a quarter (n = 34) reported interaction with
      'illegal' immigrants. Twenty-give authorities (18.4%) gave the indication to
      carry out treatment. This outpatient treatment option is mostly limited to
      patients afflicted with sexually transmitted infections with the distinct
      exception of human immunodeficiency virus/acquired immune deficiency syndrome.
      CONCLUSIONS: The study highlights the gap between legislation and the reality of
      restricted access to medical services for undocumented migrants in Germany. It
      underlines the need of increased financial and human resources in Public Health
      Authorities and, overall, the simplification of national legislation to assure
      the right to healthcare.

PMID- 25772753
TI  - Different socioeconomic inequalities exist in terms of the prevention, diagnosis
      and control of diabetes.
AB  - OBJECTIVE: To evaluate socioeconomic disadvantage in prevalence, awareness and
      control of diabetes in universal coverage healthcare system. METHODS: Data from
      the fifth KNHNES (2010-12) were analyzed. The sample included 10,208 individuals
      with diabetes aged >=30 years. Diabetes was defined by (i) a self-reported
      previous diagnosis of diabetes made by a physician, (ii) the current use of oral
      hypoglycaemic agents and/or insulin or (iii) fasting plasma glucose >=126 mg/dl.
      Subjects who were first diagnosed by the survey were classified as 'undiagnosed'.
      Inadequate control was defined as HbA1c >=6.5%. RESULTS: It was estimated that
      26.4% of subjects with diabetes were not aware of their condition and 73.1% of
      cases of diabetes were not adequately controlled. Inequalities in socioeconomic
      status were related to the diabetes prevalence in both men and women. Educational
      level was not predictive of diagnosis or control in men or women, whereas lower
      household income level was associated with diagnosis in men only. CONCLUSIONS:
      This widespread lack of awareness and inadequate control underscore the need for
      intensive efforts in these domains. Monitoring is expected to highlight the gaps
      in the preventive and care services offered to the most vulnerable individuals
      and it may induce governments and practitioners to address these issues.

PMID- 25772754
TI  - Developmental and Subcellular Organization of Single-Cell C4 Photosynthesis in
      Bienertia sinuspersici Determined by Large-Scale Proteomics and cDNA Assembly
      from 454 DNA Sequencing.
AB  - Kranz C4 species strictly depend on separation of primary and secondary carbon
      fixation reactions in different cell types. In contrast, the single-cell C4
      (SCC4) species Bienertia sinuspersici utilizes intracellular compartmentation
      including two physiologically and biochemically different chloroplast types;
      however, information on identity, localization, and induction of proteins
      required for this SCC4 system is currently very limited. In this study, we
      determined the distribution of photosynthesis-related proteins and the induction
      of the C4 system during development by label-free proteomics of subcellular
      fractions and leaves of different developmental stages. This was enabled by
      inferring a protein sequence database from 454 sequencing of Bienertia cDNAs.
      Large-scale proteome rearrangements were observed as C4 photosynthesis developed
      during leaf maturation. The proteomes of the two chloroplasts are different with
      differential accumulation of linear and cyclic electron transport components,
      primary and secondary carbon fixation reactions, and a triose-phosphate shuttle
      that is shared between the two chloroplast types. This differential protein
      distribution pattern suggests the presence of a mRNA or protein-sorting mechanism
      for nuclear-encoded, chloroplast-targeted proteins in SCC4 species. The combined
      information was used to provide a comprehensive model for NAD-ME type carbon
      fixation in SCC4 species. 

PMID- 25772755
TI  - Equine platelet lysate as an alternative to fetal bovine serum in equine
      mesenchymal stromal cell culture - too much of a good thing?
AB  - REASONS FOR PERFORMING STUDY: Multipotent mesenchymal stromal cells (MSC) are
      often culture-expanded in vitro. Presently, expansion medium (EM) for MSC is
      supplemented with fetal bovine serum (FBS). However, increasing cost, variable
      composition and potential risks associated with bovine antigens call for
      alternatives. Platelet lysate (PL) has shown promise as an alternative
      supplement. OBJECTIVES: To determine how equine umbilical cord blood (CB) MSC
      proliferate in EM enriched with PL or FBS at various concentrations. STUDY
      DESIGN: Randomised dose escalation study. METHODS: Platelet concentrate was
      generated from 5 equine whole blood samples through a double centrifugation
      method and standardised to 1 * 10(12) platelets/l prior to a freeze/thaw cycle to
      produce PL. Pooled PL or pooled FBS was added to EM at concentrations of 5% to
      60%. Proliferation of 4 equine CB-MSC cultures was determined after 4 days using
      a resazurin semiquantitative assay. RESULTS: Cord blood-MSC proliferated with a
      dose-dependent response with no significant difference found between PL and FBS
      up to a 30% concentration. Beyond 30%, proliferation fell in the PL-cultured
      cells, while continued dose-dependent proliferation was noted in the FBS-cultured
      cells. Despite reduced cell numbers in high PL concentrations, live/dead staining
      revealed that adherent cells remained viable. CONCLUSIONS: Expansion medium
      enriched with PL can support short-term equine CB-MSC proliferation at
      conventional culture concentrations. Based on the unexpected suppression of CB
      MSC at higher PL concentrations, an in vivo dose study is indicated to
      investigate if combinational therapies of CB-MSC and platelet-rich plasma are
      associated with synergistic or antagonistic effect on CB-MSC function.

PMID- 25772756
TI  - Motesanib with or without panitumumab plus FOLFIRI or FOLFOX for the treatment of
      metastatic colorectal cancer.
AB  - PURPOSE: This study assessed the safety, efficacy, and pharmacokinetics of
      motesanib, a multitargeted small molecule angiogenesis inhibitor, with and
      without panitumumab, in combination with FOLFIRI or FOLFOX in patients with
      metastatic colorectal cancer (mCRC). METHODS: This open-label, phase 1b, two
      part, multicenter study in patients with mCRC and <=1 prior treatment evaluated
      escalating doses (50, 75, 100, or 125 mg QD, 75 mg BID) of motesanib with
      panitumumab and chemotherapy (Part 1) and the target dose of motesanib with
      chemotherapy (Part 2). RESULTS: At 17 sites in the USA and Australia, 119
      patients were enrolled between December 2004 and February 2010. In Part 1
      [motesanib plus panitumumab/FOLFIRI (n = 36) or plus panitumumab/FOLFOX (n =
      17)], all motesanib doses tested were tolerated and 125 mg QD was deemed the
      target dose. Following toxicity results for combination therapy in other trials,
      panitumumab was withdrawn from the study. Part 2 evaluated motesanib 125 mg with
      chemotherapy [FOLFIRI (n = 37); FOLFOX (n = 29)]. The primary endpoint, objective
      response rate in patients with measurable disease by RECIST, was 20 % overall and
      was higher among patients receiving first-line (27 % overall; FOLFOX, 24 %;
      FOLFIRI, 27 %) compared with second-line therapy (14 % overall; FOLFOX, 0 %;
      FOLFIRI, 20 %). The most common adverse events were diarrhea, nausea, fatigue,
      and hypertension. We observed a low rate of cholecystitis [3 of 119 (2.5 %)], a
      known adverse event of motesanib and other small molecule VEGF inhibitors.
      CONCLUSIONS: Motesanib 125 mg QD in combination with FOLFIRI or FOLFOX
      chemotherapy was tolerated and demonstrated modest efficacy in first-/second-line
      mCRC.

PMID- 25772757
TI  - Organic cation transporter OCT6 mediates cisplatin uptake and resistance to
      cisplatin in lung cancer.
AB  - PURPOSE: The purposes of this study were to determine whether organic cation
      transporters (OCTs) can mediate platinum uptake, and whether OCT down-regulation
      confers resistance against cisplatin (CDDP) in cancer cells. METHODS: Two lung
      cancer cell lines, PC-6 and PC-14, and their CDDP-resistant derivatives, PC
      6/CDDP and PC-14/CDDP, were analyzed. OCT expression levels were assayed using
      quantitative RT-PCR and Western blotting. Additionally, the effect of OCT6
      overexpression, induced by transfection of the OCT6 gene SLC22A16 using a forced
      expression vector, on cellular sensitivity to CDDP and on intracellular platinum
      accumulation was measured using PC-14/CDDP cells. RESULTS: Both gene and protein
      expression of OCT6 were decreased in both CDDP-resistant cell lines compared with
      their expression in their respective parental cells. Intracellular accumulation
      of platinum was decreased in PC-14/CDDP cells compared with the parental cells
      after CDDP treatment. Furthermore, OCT6 overexpression induced by transfection of
      the OCT6 gene (SLC22A16) forced expression vector-sensitized PC-14/CDDP cells to
      CDDP and oxaliplatin (L-OHP) concomitant with increased intracellular
      concentration of platinum. CONCLUSION: OCT6 is a mediator of platinum uptake in
      cancer cells, and down-regulation of OCT6 is possibly one of the mechanisms of
      resistance against cisplatin in lung cancer.

PMID- 25772758
TI  - KSP inhibitor SB743921 induces death of multiple myeloma cells via inhibition of
      the NF-kappaB signaling pathway.
AB  - SB743921 is a potent inhibitor of the spindle protein kinesin and is being
      investigated in ongoing clinical trials for the treatment of myeloma. However,
      little is known about the molecular events underlying the induction of cell death
      in multiple myeloma (MM) by SB743921, alone or in combination treatment. Here, we
      report that SB743921 induces mitochondria-mediated cell death via inhibition of
      the NF-kappaB signaling pathway, but does not cause cell cycle arrest in KMS20 MM
      cells. SB743921-mediated inhibition of the NF-kappaB pathway results in reduced
      expression of SOD2 and Mcl-1, leading to mitochondrial dysfunction. We also found
      that combination treatment with SB743921 and bortezomib induces death in
      bortezomib-resistant KMS20 cells. Altogether, these data suggest that treatment
      with SB743921 alone or in combination with bortezomib offers excellent
      translational potential and promises to be a novel MM therapy.

PMID- 25772760
TI  - Self-renewal and circulating capacities of metastatic hepatocarcinoma cells
      required for collaboration between TM4SF5 and CD44.
AB  - Tumor metastasis involves circulating and tumor-initiating capacities of
      metastatic cancer cells. Hepatic TM4SF5 promotes EMT for malignant growth and
      migration. Hepatocellular carcinoma (HCC) biomarkers remain unexplored for
      metastatic potential throughout metastasis. Here, novel TM4SF5/CD44 interaction
      mediated self-renewal and circulating tumor cell (CTC) capacities were
      mechanistically explored. TM4SF5-dependent sphere growth was correlated with
      CD133+, CD24-, ALDH activity, and a physical association between CD44 and TM4SF5.
      The TM4SF5/CD44 interaction activated c-Src/STAT3/Twist1/B mi1 signaling for
      spheroid formation, while disturbing the interaction, expression, or activity of
      any component in this signaling pathway inhibited spheroid formation. In serial
      xenografts of less than 5,000 cells/injection, TM4SF5-positive tumors exhibited
      locally-increased CD44 expression, suggesting tumor cell differentiation. TM4SF5
      positive cells were identified circulating in blood 4 to 6 weeks after orthotopic
      liver- injection. Anti-TM4SF reagents blocked their metastasis to distal
      intestinal organs. Altogether, our results provide evidence that TM4SF5 promotes
      self-renewal and CTC properties supported by CD133+/TM4SF5+/CD44+(TM4SF5
      bound)/ALDH+/CD24-markers during HCC metastasis.

PMID- 25772759
TI  - FZD6 expression is negatively regulated by miR-199a-5p in human colorectal
      cancer.
AB  - Colorectal cancer (CRC), the third most common cancer worldwide, also has the
      highest rate of cancer-related morbidity and mortality. WNT signaling is
      initiated by binding of WNT to various receptors, including frizzleds (FZDs), and
      plays a critical role in CRC and other tumor development by regulating
      proliferation, differentiation, migration, apoptosis, and polarity. Among the
      members of the FZD family, FZD6 is broadly expressed in various tissues, and its
      overexpression has been reported in several cancers, suggesting an important role
      in cancer development. In this study, we investigated the expression of FZD6 in
      patients with CRC and found it to be increased in tumors, as compared to paired
      adjacent non-tumor tissues. Additionally, we found that FZD6 expression was
      negatively regulated by miR199a5p in CRC cells. These results suggest that
      overexpression of FZD6, mediated by reduced expression of miR-199a-5p, may play
      an important role in the development of CRC.

PMID- 25772761
TI  - Prevalence of 'surfer's ear' in Cornish surfers.
AB  - OBJECTIVES: To establish the prevalence of external auditory canal exostosis
      ('surfer's ear') in Cornish surfers and investigate the potential impact on
      healthcare. METHOD: A total of 105 surfers were interviewed and otologically
      assessed on popular Cornish beaches. The degree of exostosis was graded as mild,
      moderate or severe. RESULTS: The prevalence of external auditory canal exostosis
      was 63.81 per cent (33.33 per cent mild, 18.10 per cent moderate and 12.38 per
      cent severe). The degree of exostosis showed a significant correlation with
      absolute cold-water exposure time. However, there was individual variation in
      susceptibility to external auditory canal exostosis; 12 per cent of surfers with
      excessive cold-water exposure showed no exostosis. Regression analysis of
      surgical operations performed at the Royal Cornwall Hospital for exostosis over
      the last 13 years revealed an average increase of 1.23 operations per year, with
      an average of 13 cases per year over the last 9 years. CONCLUSION: Exostosis of
      the external auditory canal is common in Cornish surfers. There appears to be
      individual variation in terms of susceptibility to this condition. The possible
      reasons for this are discussed. The increase in the technically difficult
      surgical operations performed for exostosis is likely to have implications for
      health resources in the future.

PMID- 25772762
TI  - Patients' Preferences Related to Benefits, Risks, and Formulations of
      Schizophrenia Treatment.
AB  - OBJECTIVE: The objective of this study was to quantify patients' preferences
      related to benefits and risks of antipsychotic treatments for schizophrenia and
      to assess the relative importance of treatment attributes and adherence. METHODS:
      Treatment-related preferences among U.S. residents with a self-reported physician
      diagnosis of schizophrenia were assessed via a discrete-choice experiment.
      Patients chose between competing hypothetical scenarios characterized by
      improvements in positive symptoms, negative symptoms, and social functioning;
      incidence of weight gain, extrapyramidal symptoms (EPS), hyperprolactinemia, and
      hyperglycemia; and medication formulation. Preferences were estimated by using a
      random-parameters logit model, and the impact of adherence was estimated with
      conditional logit models. RESULTS: The final sample consisted of 271 patients.
      Complete improvement in positive symptoms was the most preferred outcome
      (relative importance score of 10.0), followed by elimination of hyperglycemia
      (3.6, 95% confidence interval [CI]=2.6-4.6), improvement in negative symptoms
      (3.0, CI=1.6-4.3), reduced weight gain (2.6, CI=1.2-4.0), avoidance of
      hyperprolactinemia (1.7, CI=.9-2.6), improved social functioning (1.5, CI=.4
      2.5), and avoidance of EPS (1.0, CI=.3-1.8). Patients judged a daily pill
      superior to monthly injections (p<.01) and monthly injections superior to
      injections every three months (p<.01) for adherent patients and monthly
      injections superior to a daily pill for nonadherent patients (p=.01).
      CONCLUSIONS: Persons who self-identified as having schizophrenia judged
      improvement in positive symptoms as the most important treatment benefit.
      Hyperglycemia was identified as the most important adverse event. Patients judged
      oral formulations to be better than monthly injections for adherent patients and
      monthly injections to be a better choice for nonadherent patients.

PMID- 25772763
TI  - Relationship Between General Illness and Mental Health Service Use and
      Expenditures Among Racially-Ethnically Diverse Adults >=65 Years.
AB  - OBJECTIVES: The association of general medical illness and mental health service
      use among older adults from racial-ethnic minority groups is an important area of
      study given the disparities in mental health and general medical services and the
      low use of mental health services in this population. The purpose of this report
      is to describe the impact of comorbid general medical illness on mental health
      service use and expenditures among older adults and to evaluate disparities in
      mental health service use and expenditures in a racially-ethnically diverse
      sample of older adults with and without comorbid general medical illness.
      METHODS: Data were obtained from the Medical Expenditure Panel Survey (years 2004
      2011). The sample included 1,563 whites, 519 African Americans, and 642 Latinos
      (N=2,724) age >=65 with probable mental illness. Two-part generalized linear
      models were used to estimate and compare mental health service use among adults
      with and without a comorbid general medical illness. RESULTS: Mental health
      service use was more likely for older adults with comorbid general medical
      illness than for those without it. Once mental health services were accessed, no
      differences in mental health expenditures were found. Comorbid general medical
      illness increased the likelihood of mental health service use by older whites and
      Latinos. However, the presence of comorbidity did not affect racial-ethnic
      disparities in mental health service use. CONCLUSIONS: This study highlighted the
      important role of comorbid general medical illness as a potential contributor to
      using mental health services and suggests intervention strategies to enhance
      engagement in mental health services by older adults from racial-ethnic minority
      groups.

PMID- 25772765
TI  - Bringing Recovery to Practice: Improving Provider Competencies and Promoting
      Positive Outcomes.
AB  - The concept of "recovery" in the context of treating mental illness-including
      serious mental illness-has been recognized as a central guiding principle for the
      orientation of behavioral health systems, including the delivery of effective
      treatment and services, and the development of practices, policies, and systems
      change. As the adoption of recovery-oriented care expands, there is a need to
      prepare the mental health and addictions workforce with recovery-based clinical
      skills and practice delivery approaches. In response, the Substance Abuse and
      Mental Health Services Administration (SAMHSA) created an innovative workforce
      collaborative to increase clinician skills to deliver evidence-based, recovery
      oriented treatment, services, and supports. This column describes that
      collaborative-the Recovery to Practice project. 

PMID- 25772764
TI  - Implementing Coordinated Specialty Care for Early Psychosis: The RAISE Connection
      Program.
AB  - OBJECTIVE: The RAISE (Recovery After an Initial Schizophrenia Episode) Connection
      Program Implementation and Evaluation Study developed tools necessary to
      implement and disseminate an innovative team-based intervention designed to
      promote engagement and treatment participation, foster recovery, and minimize
      disability among individuals experiencing early psychosis. This article describes
      the treatment model and reports on service utilization and outcomes. It was
      hypothesized that individuals' symptoms and functioning would improve over time.
      METHODS: A total of 65 individuals in RAISE Connection Program treatment across
      two sites (Baltimore and New York City) were enrolled and received services for
      up to two years. Primary outcomes, including social and occupational functioning
      and symptoms, were evaluated. Trajectories for individuals' outcomes over time
      were examined with linear and quadratic mixed-effects models with repeated
      measures. RESULTS: Measures of occupational and social functioning improved
      significantly over time, symptoms declined, and rates of remission improved.
      Visits were most frequent during the first three months, with a mean+/-SD of
      23.2+/-11.5 unduplicated staff encounters per quarter. Such encounters decreased
      to 8.8+/-5.2 in the final quarter of year 2. CONCLUSIONS: The overall project was
      successful in that the treatment program was delivered and tools useful to other
      clinical settings were produced. The strengths of this study lie in the
      demonstrated feasibility of delivering the coordinated specialty care model and
      the associated high rates of engagement among individuals who are typically
      difficult to engage in treatment. Notwithstanding the lack of a built-in
      comparison group, participant outcomes were promising, with improvements
      comparable to those seen with other successful interventions.

PMID- 25772766
TI  - The NAVIGATE Program for First-Episode Psychosis: Rationale, Overview, and
      Description of Psychosocial Components.
AB  - Comprehensive coordinated specialty care programs for first-episode psychosis
      have been widely implemented in other countries but not in the United States. The
      National Institute of Mental Health's Recovery After an Initial Schizophrenia
      Episode (RAISE) initiative focused on the development and evaluation of first
      episode treatment programs designed for the U.S. health care system. This article
      describes the background, rationale, and nature of the intervention developed by
      the RAISE Early Treatment Program project-known as the NAVIGATE program-with a
      particular focus on its psychosocial components. NAVIGATE is a team-based,
      multicomponent treatment program designed to be implemented in routine mental
      health treatment settings and aimed at guiding people with a first episode of
      psychosis (and their families) toward psychological and functional health. The
      core services provided in the NAVIGATE program include the family education
      program (FEP), individual resiliency training (IRT), supported employment and
      education (SEE), and individualized medication treatment. NAVIGATE embraces a
      shared decision-making approach with a focus on strengths and resiliency and on
      collaboration with clients and family members in treatment planning and reviews.
      The NAVIGATE program has the potential to fill an important gap in the U.S.
      health care system by providing a comprehensive intervention specially designed
      to meet the unique treatment needs of persons recovering from a first episode of
      psychosis. A cluster-randomized controlled trial comparing NAVIGATE with usual
      community care has recently been completed. 

PMID- 25772767
TI  - Contained morcellation using the GelPOINT advance access platforms and 3M Steri
      Drape endobag.
AB  - OBJECTIVE: To report a technique that safely allows power and hand morcellation
      for laparoscopic hysterectomy and myomectomy specimens in a contained fashion in
      the event of unsuspected uterine sarcoma or leiomyosarcoma. DESIGN: Video article
      introducing a method for enclosed tissue morcellation for laparoscopic specimens.
      SETTING: Hospital of an academic-based practice. PATIENT(S): Two patients
      underwent laparoscopic hysterectomy: a 57-year-old G7 P5025 female for leiomyoma,
      anemia, and a history of CIN-3; and a 38-year-old G0P0 female with a 10-year
      history of pelvic pain and severe dysmenorrhea who failed medical therapy.
      INTERVENTION(S): A technique using the GelPOINT Platform incision extender system
      and GelSeal Cap (GSP) Advanced Access Platform and a 50 cm * 50 cm 3M Steri-Drape
      endobag for enclosed intracorporeal and extracorporeal tissue morcellation of
      laparoscopic specimens. MAIN OUTCOME MEASURE(S): For training purposes, we used a
      pelvic simulator and cadaver to describe the step-by-step process and
      troubleshoot issues to optimize intra- and extracorporeal morcellation. This
      allowed for easier implementation on the live patient. RESULT(S): Simulation
      training and the cadaver model provided a learning platform for contained
      internal power and external hand morcellation, accelerating the learning curve in
      its application to the live patient. CONCLUSION(S): The GSP and 3M Steri-Drape
      endobag is an alternative for laparoscopic power or hand morcellation. Using
      simulation training helped transition this technique to the live patient,
      allowing for easy and safe removal of tissue specimens and minimizing the
      potential for tissue seeding and dissemination.

PMID- 25772768
TI  - Antimullerian hormone levels decrease in female-to-male transsexuals using
      testosterone as cross-sex therapy.
AB  - OBJECTIVE: To investigate the effect of hormonal androgenic treatment on
      antimullerian hormone (AMH) serum levels in female-to-male (FtM) transsexuals.
      Polycystic ovary syndrome (PCOS) is associated with elevated AMH levels. Some
      hypothesize that the high AMH level is a consequence of androgen-induced
      excessive development of small antral follicles. However, this role of androgens
      is not yet clear. DESIGN: Observational, prospective, cohort study. SETTING:
      Tertiary academic medical center. PATIENT(S): Twenty-two FtM transsexuals,
      healthy native females receiving cross-sex hormone therapy/androgenic treatment.
      INTERVENTION(S): Androgenic treatment with testosterone (T) and an aromatase
      inhibitor while endogenous hormone secretion was suppressed with the use of a
      GnRH agonist. MAIN OUTCOME MEASURE(S): Hormone concentrations were measured
      before and after androgenic treatment (administration of T and aromatase
      inhibitor). Measured hormones: AMH, inhibin B, T, androstenedione, DHEAS, E2,
      SHBG, LH, and FSH. RESULT(S): AMH concentrations were significantly lower after
      androgenic treatment (4.4 +/- 4.4 MUg/L vs. 1.4 +/- 2.1 MUg/L). Androgenic
      treatment resulted in a strong suppression of AMH secretion over a relative short
      period of 16 weeks. CONCLUSION(S): Our data underscore the likely important role
      of androgens in the dynamics of folliculogenesis. It challenges the idea that
      androgens induce high AMH levels, which is gaining more interest nowadays as an
      important particular PCOS feature. This strong decline furthermore indicates that
      AMH must be interpreted in the context of other reproductive endocrine
      conditions. CLINICAL TRIAL REGISTRATION NUMBER: NTR2493.

PMID- 25772769
TI  - Autophagy is upregulated in ovarian endometriosis: a possible interplay with p53
      and heme oxygenase-1.
AB  - OBJECTIVE: To evaluate the occurrence of the autophagic process in ovarian
      endometriomas compared with eutopic endometrium of affected women and with normal
      endometrium of healthy women. DESIGN: Biochemical and molecular study in tissue
      extracts. SETTING: University cellular pathology laboratory and university
      hospital. PATIENT(S): Patients with ovarian endometriosis (n = 13) and healthy
      women (n = 18). INTERVENTION(S): Specimens of endometrium were obtained by
      hysteroscopy from patients with endometriosis and from healthy control subjects;
      specimens of ovarian endometriomas were collected by laparoscopy. All patients
      underwent surgery after the end of menstrual bleeding, resulting in most of our
      patients (approximately 80% in each group) being in the proliferative phase. MAIN
      OUTCOME MEASURE(S): Autophagy was evaluated by Western blot analysis of
      biochemical markers (LC3-II, LC3-II/LC3-I ratio and p62) and by quantitative real
      time polymerase chain reaction of autophagy-related genes (ATG14, BECN1, ATG7,
      and LC3B); apoptosis-related (p53 and Bcl-2) and oxidative stress-related (heme
      oxygenase-1) proteins were also evaluated by Western blot analysis. RESULT(S):
      All tested biochemical markers and messenger RNA levels of autophagy-related
      genes showed a significant up-regulation of autophagy in ovarian endometriomas
      compared with eutopic endometria of affected or healthy women. Moreover, a
      significant decrease of p53 protein and a significant increase of heme oxygenase
      1 protein was also evident in endometriomas. CONCLUSION(S): The upregulated
      autophagic process observed in ovarian endometriomas can be regarded as an
      integral part of endometriosis pathogenesis, possibly contributing to survival of
      endometriotic cells in ectopic sites and to lesion maintenance. The decreased
      susceptibility to apoptosis and the persistent oxidative stress experienced by
      endometriotic cells could favor autophagy stimulation.

PMID- 25772770
TI  - Cost-effectiveness analysis of preimplantation genetic screening and in vitro
      fertilization versus expectant management in patients with unexplained recurrent
      pregnancy loss.
AB  - OBJECTIVE: To determine whether in vitro fertilization with preimplantation
      genetic screening (IVF/PGS) is cost effective compared with expectant management
      in achieving live birth for patients with unexplained recurrent pregnancy loss
      (RPL). DESIGN: Decision analytic model comparing costs and clinical outcomes.
      SETTING: Academic recurrent pregnancy loss programs. PATIENT(S): Women with
      unexplained RPL. INTERVENTION(S): IVF/PGS with 24-chromosome screening and
      expectant management. MAIN OUTCOMES MEASURE(S): Cost per live birth. RESULT(S):
      The IVF/PGS strategy had a live-birth rate of 53% and a clinical miscarriage rate
      of 7%. Expectant management had a live-birth rate of 67% and clinical miscarriage
      rate of 24%. The IVF/PGS strategy was 100-fold more expensive, costing $45,300
      per live birth compared with $418 per live birth with expectant management.
      CONCLUSION(S): In this model, IVF/PGS was not a cost-effective strategy for
      increasing live birth. Furthermore, the live-birth rate with IVF/PGS needs to be
      91% to be cost effective compared with expectant management.

PMID- 25772771
TI  - Revisiting the fertile window.

PMID- 25772772
TI  - Circulating microRNAs as potential biomarkers for endometriosis.
AB  - OBJECTIVE: To evaluate whether microRNAs (miRNAs) associated with endometriosis
      are detectable in the circulation and could serve as potential noninvasive
      biomarkers for endometriosis. DESIGN: Case-control study. SETTING: University
      hospital. PATIENT(S): Twenty-four women with endometriosis and 24 women without
      the disease (controls). INTERVENTION(S): Serum samples collected from women
      undergoing laparoscopy for endometriosis and other benign gynecologic disease.
      MAIN OUTCOME MEASURE(S): Total RNA extracted from serum and quantitative reverse
      transcription polymerase chain reaction to determine levels of miRNA let-7a-f and
      miR-135a,b. RESULT(S): The levels of circulating let-7b and miR-135a were
      statistically significantly decreased in women with endometriosis compared with
      controls, and let-7d and 7f showed a trend toward down-regulation. Let-7b
      expression strongly correlated with serum CA-125 levels and showed the highest
      area under the curve of 0.691. When the patients were analyzed according to phase
      of the menstrual cycle, the expression of let-7b, 7c, 7d, and 7e was
      statistically significantly lower in the women with endometriosis during the
      proliferative phase. Using a logistic regression model, we evaluated the
      diagnostic power of differently expressed miRNAs; the combination of let-7b, let
      7d, and let-7f during the proliferative phase yielded the highest area under the
      curve value of 0.929 in discriminating endometriosis from controls.
      CONCLUSION(S): Several circulating miRNAs are differentially expressed in the
      sera of women with endometriosis compared with controls. The combination of serum
      let-7b, 7d, and 7f levels during the proliferative phase may serve as a
      diagnostic marker for endometriosis.

PMID- 25772773
TI  - Pregnancy-associated microRNAs in plasma as potential molecular markers of
      ectopic pregnancy.
AB  - OBJECTIVE: To investigate cell-free pregnancy-associated microRNAs as molecular
      markers for the diagnosis of ectopic pregnancy. DESIGN: Laboratory study using
      human plasma samples. SETTING: Research unit in a university hospital.
      PATIENT(S): Plasma samples from 18 women with ectopic pregnancies (EP group), 12
      women with spontaneous abortion (SA group), and 26 normal women with singleton
      pregnancies (NP group). INTERVENTION(S): Total RNAs containing small RNA
      molecules extracted from 1.2 mL of plasma. MAIN OUTCOME MEASURE(S): Plasma
      concentrations of cell-free microRNAs measured by quantitative real-time reverse
      transcriptase polymerase chain reaction. RESULT(S): Plasma concentrations of cell
      free pregnancy-associated microRNAs (miR-323-3p, miR-515-3p, miR-517a, miR-517c,
      and miR-518b) and serum concentration of human chorionic gonadotropin (hCG) were
      confirmed to have statistically significantly different plasma or serum
      concentrations in women with EP, SA, or NP. There was no statistically
      significant difference in the plasma concentrations of cell-free miR-21 between
      the three groups. By correlation coefficient analysis, no relationship was
      detected between serum hCG levels and plasma cell-free miR-517c, miR-515-3p, miR
      517a, miR-518b, miR-323-3p, or miR-21 levels. Plasma concentrations of cell-free
      miR-517a could distinguish EP/SA from NP, yielding an area under the curve of
      0.9654 (95% confidence interval, 0.9172-1.0). Plasma concentrations of cell-free
      miR-323-3p could distinguish EP from SA, yielding an area under the curve of
      0.7454 (95% confidence interval, 0.5558-0.9349). CONCLUSION(S): Cell-free
      pregnancy-associated microRNAs have potential as molecular markers of ectopic
      pregnancy.

PMID- 25772774
TI  - Time-lapse monitoring of zona pellucida-free embryos obtained through in vitro
      fertilization: a retrospective case series.
AB  - OBJECTIVE: To report time-lapse monitoring of human oocytes in which the damaged
      zona pellucida was removed, producing zona-free (ZF) oocytes that were cultured
      until the blastocyst stage in time-lapse incubators. DESIGN: Retrospective case
      series. SETTING: Private infertility clinic. PATIENT(S): Infertile patients (n =
      32) undergoing minimal ovarian stimulation or natural cycle IVF treatment between
      October 2012 and June 2014. INTERVENTION(S): Intracytoplasmic sperm injection
      (ICSI) fertilization of ZF oocytes, prolonged embryo culture in time-lapse
      incubators, elective vitrification, and subsequent single vitrified-thawed
      blastocyst transfer (SVBT). MAIN OUTCOME MEASURE(S): Rate of fertilization,
      cleavage and blastocyst development, live-birth rate per SVBT cycle. RESULT(S):
      In spite of advanced maternal age (39 +/- 4.2; range, 30-46 years), good
      fertilization (94%), cleavage (94%), and blastocyst development rates (38%) were
      reached after fertilization and culturing of ZF oocytes/embryos. All thawed ZF
      blastocysts survived, and up to this date seven SVBT transfers were performed,
      yielding three (43%) term live births with healthy newborns. CONCLUSION(S): Time
      lapse imagery gives a unique insight into the dynamics of embryo development in
      ZF embryos. Moreover, our case series demonstrate that an oocyte with a damaged
      zona pellucida that has been removed could be successfully fertilized with ICSI,
      cultured until blastocyst stage in a time-lapse incubator and vitrified
      electively for subsequent use.

PMID- 25772775
TI  - Vanishing twin syndrome: is it associated with adverse perinatal outcome?
AB  - OBJECTIVE: To evaluate whether vanishing twin syndrome (VTS) is associated with
      adverse perinatal outcome. DESIGN: A retrospective cohort study investigating the
      impact of VTS on perinatal outcome was conducted. Parturients were classified
      into three groups: those pregnancies that started with double fetal sacs and
      spontaneously reduced into one (VTS), those with dichorionic twins, and those
      with singleton pregnancies. Statistical analysis included multiple logistic
      regression models to control for possible confounders. SETTING: Tertiary
      university medical center. PATIENT(S): The study involved 252,994 singleton
      deliveries between the years 1988 and 2012. INTERVENTION(S): None. MAIN OUTCOME
      MEASURE(S): The impact of VTS on perinatal outcome. RESULT(S): During the study
      period, 278 pregnancies with VTS were compared with 1,801 pregnancies of
      dichorionic twins and 252,994 pregnancies of singletons. A significant linear
      association was documented among the three groups and various adverse outcomes,
      including gestational diabetes mellitus (GDM), intrauterine growth restriction
      (IUGR), very low birth weight (VLBW), and perinatal mortality. The higher risk
      was noted in the VTS group, and the lowest in singletons. Using multivariable
      logistic regression models, while controlling for confounders such as fertility
      treatment and maternal age, VTS (as compared with singletons) was found to be an
      independent risk factor for several adverse perinatal outcomes including GDM,
      IUGR, VLBW, low Apgar scores, and perinatal mortality (adjusted odds ratios with
      their respective 95% confidence intervals, 1.4 [1.01-2.0], 2.7 [1.7-4.3], 6.9
      [4.7-10.2], 1.9 [1.1-3.3], 2.4 [1.2-4.5]). CONCLUSION(S): Pregnancies with VTS
      are associated with an adverse perinatal outcome, even after controlling for
      confounders such as fertility treatment and maternal age.

PMID- 25772776
TI  - Utilization of PARAFAC-Modeled Excitation-Emission Matrix (EEM) Fluorescence
      Spectroscopy to Identify Biogeochemical Processing of Dissolved Organic Matter in
      a Northern Peatland.
AB  - In this study, we contrast the fluorescent properties of dissolved organic matter
      (DOM) in fens and bogs in a Northern Minnesota peatland using excitation emission
      matrix fluorescence spectroscopy with parallel factor analysis (EEM-PARAFAC). EEM
      PARAFAC identified four humic-like components and one protein-like component and
      the dynamics of each were evaluated based on their distribution with depth as
      well as across sites differing in hydrology and major biological species. The
      PARAFAC-EEM experiments were supported by dissolved organic carbon measurements
      (DOC), optical spectroscopy (UV-Vis), and compositional characterization by
      ultrahigh resolution Fourier transform ion cyclotron resonance mass spectroscopy
      (FT-ICR MS). The FT-ICR MS data indicate that metabolism in peatlands reduces the
      molecular weights of individual components of DOM, and oxygen-rich less aromatic
      molecules are selectively biodegraded. Our data suggest that different hydrologic
      and biological conditions within the larger peat ecosystem drive molecular
      changes in DOM, resulting in distinctly different chemical compositions and
      unique fluorescent fingerprints. PARAFAC modeling of EEM data coupled with
      ultrahigh resolution FT-ICR MS has the potential to provide significant molecular
      based information on DOM composition that will support efforts to better
      understand the composition, sources, and diagenetic status of DOM from different
      terrestrial and aquatic systems. 

PMID- 25772777
TI  - Human Immunodeficiency Virus-Associated Diarrhea: Still an Issue in the Era of
      Antiretroviral Therapy.
AB  - Over half of patients with human immunodeficiency virus (HIV) experience diarrhea
      that contributes negatively to quality of life and adherence to antiretroviral
      therapy (ART). Opportunistic infectious agents that cause diarrhea in patients
      with HIV span the array of protozoa, fungi, viruses, and bacteria. With global
      use of ART, the incidence of diarrhea because of opportunistic infections has
      decreased; however, the incidence of noninfectious diarrhea has increased. The
      etiology of noninfectious diarrhea in patients with HIV is multifactorial and
      includes ART-associated diarrhea and gastrointestinal damage related to HIV
      infection (i.e., HIV enteropathy). A basic algorithm for the diagnosis of
      diarrhea in patients with HIV includes physical examination, a review of medical
      history, assessment of HIV viral load and CD4+ T cell count, stool microbiologic
      assessment, and endoscopic evaluation, if needed. For patients with negative
      diagnostic results, the diagnosis of noninfectious diarrhea may be considered.
      Pharmacologic options for the treatment of noninfectious diarrhea are primarily
      supportive; however, the use of many unapproved agents is based on unstudied and
      anecdotal information. In addition, these agents can be associated with treatment
      limiting adverse events (AEs), such as drug-drug interactions with ART regimens,
      abuse liability, and additional gastrointestinal AEs. Currently, crofelemer, an
      antisecretory agent, is the only therapy approved in the USA for the symptomatic
      relief of noninfectious diarrhea in patients with HIV on ART. 

PMID- 25772779
TI  - E-cadherin Is Important for the Maintenance of Intestinal Epithelial Homeostasis
      Under Basal and Inflammatory Conditions.

PMID- 25772778
TI  - Patients with Crohn's Disease Are More Likely to Remain on Biologics than
      Immunomodulators: A Meta-Analysis of Treatment Durability.
AB  - BACKGROUND AND AIM: The comparative effectiveness of treatments for moderate-to
      severe Crohn's disease can be influenced by the likelihood of remaining on
      medication. We aimed to clarify this treatment durability by assessing subject
      discontinuations from clinical trials in the context of treatment efficacy.
      METHODS: We conducted a literature search for double-blind RCT of Crohn's disease
      therapies recommended in international guidelines or with recent positive phase
      III trial results. Durability was defined through study discontinuation due to
      adverse events or disease exacerbation represented by number needed to
      discontinue (NND). Efficacy was defined as clinical remission represented by
      number needed to treat (NNT). The primary endpoint was NND/NNT, with a higher
      value representing more durable and effective treatment. RESULTS: Treatment with
      azathioprine/6-mercaptopurine (AZA/6MP) was associated with more discontinuations
      than with clinical remission (NND/NNT = 0.92) in maintenance trials. For
      induction, methotrexate was associated with similar rates of discontinuations and
      remission (NND/NNT = 1.4). In one maintenance trial, the remission rate for
      methotrexate was greater than the study discontinuation rate (NND/NNT = 23.3). In
      contrast, anti-TNF trials revealed greater durability among induction (no excess
      discontinuation) and maintenance (NND/NNT = 37.9) trials. Trials of anti
      trafficking agents had fewer discontinuations in the drug treatment arms than
      placebo resulting in most favorable NND/NNT ratios. CONCLUSIONS: For patients
      with Crohn's disease, biologic therapies had higher durability than
      immunomodulators for induction and maintenance therapy. We also report the
      results of a novel NND/NNT ratio that should be validated in a prospective head
      to-head placebo-controlled trial.

PMID- 25772780
TI  - Mechanisms of allergic disease - environmental and genetic determinants for the
      development of allergy.
AB  - Allergic disease can be viewed as an early manifestation of immune dysregulation.
      Environmental exposures including maternal inflammation, diet, nutrient balance,
      microbial colonization and toxin exposures can directly and indirectly influence
      immune programming in both pregnancy and the postnatal period. The intrauterine
      microclimate is critical for maternal and fetal immunological tolerance to
      sustain viable pregnancy, but appears susceptible to environmental conditions.
      Targeting aspects of the modern environment that promote aberrant patterns of
      immune response is logical for interventions aimed at primary prevention of
      allergic disease. Defining the mechanisms that underpin both natural and
      therapeutic acquisition of immunological tolerance in childhood will provide
      insights into the drivers of persistent immune dysregulation. In this review, we
      summarize evidence that allergy is a consequence of intrauterine and early life
      immune dysregulation, with specific focus on contributing environmental risk
      factors occurring preconception, in utero and in the early postnatal period. We
      explore the immunological mechanisms which underpin tolerance and persistence of
      allergic disease during childhood. It is likely that future investigations within
      these two domains will ultimately provide a road map for the primary prevention
      of allergic disease. 

PMID- 25772781
TI  - Linkage and association analysis of obesity traits reveals novel loci and
      interactions with dietary n-3 fatty acids in an Alaska Native (Yup'ik)
      population.
AB  - OBJECTIVE: To identify novel genetic markers of obesity-related traits and to
      identify gene-diet interactions with n-3 polyunsaturated fatty acid (n-3 PUFA)
      intake in Yup'ik people. MATERIAL AND METHODS: We measured body composition,
      plasma adipokines and ghrelin in 982 participants enrolled in the Center for
      Alaska Native Health Research (CANHR) Study. We conducted a genome-wide SNP
      linkage scan and targeted association analysis, fitting additional models to
      investigate putative gene-diet interactions. Finally, we performed bioinformatic
      analysis to uncover likely candidate genes within the identified linkage peaks.
      RESULTS: We observed evidence of linkage for all obesity-related traits,
      replicating previous results and identifying novel regions of interest for
      adiponectin (10q26.13-2) and thigh circumference (8q21.11-13). Bioinformatic
      analysis revealed DOCK1, PTPRE (10q26.13-2) and FABP4 (8q21.11-13) as putative
      candidate genes in the newly identified regions. Targeted SNP analysis under the
      linkage peaks identified associations between three SNPs and obesity-related
      traits: rs1007750 on chromosome 8 and thigh circumference (P=0.0005), rs878953 on
      chromosome 5 and thigh skinfold (P=0.0004), and rs1596854 on chromosome 11 for
      waist circumference (P=0.0003). Finally, we showed that n-3 PUFA modified the
      association between obesity related traits and two additional variants (rs2048417
      on chromosome 3 for adiponectin, P for interaction=0.0006 and rs730414 on
      chromosome 11 for percentage body fat, P for interaction=0.0004). CONCLUSIONS:
      This study presents evidence of novel genomic regions and gene-diet interactions
      that may contribute to the pathophysiology of obesity-related traits among Yup'ik
      people.

PMID- 25772782
TI  - Receptive range analysis of a mouse odorant receptor subfamily.
AB  - Mammals deploy a large array of odorant receptors (ORs) to detect and distinguish
      a vast number of odorant molecules. ORs vary widely in the type of odorant
      structures recognized and in the breadth of molecular receptive range (MRR), with
      some ORs recognizing a small group of closely related molecules and other ORs
      recognizing a wide range of structures. While closely related ORs have been shown
      to have similar MRRs, the functional relationships among less closely related ORs
      are unclear. We screened a small group of ORs with a diverse odorant panel to
      identify a new odorant-OR pairing (unsaturated aldehydes and MOR263-3). We then
      extensively screened MOR263-3 and a series of additional MORs related to MOR263-3
      in various ways. MORs related by phylogenetic analysis (several other members of
      the MOR263 subfamily) had MRRs that overlapped with the MRR of MOR263-3, even
      with amino acid identity as low as 48% (MOR263-2). MOR171-17, predicted to be
      functionally related to MOR263-3 by an alternative bioinformatic analysis, but
      with only 39% amino acid identity, had a distinct odorant specificity. Our
      results support the use of phylogenetic analysis to predict functional
      relationships among ORs with relatively low amino acid identity. We screened a
      small group of mouse odorant receptors (MORs) with a diverse odorant panel to
      identify a new odorant-OR pairing (unsaturated aldehydes and MOR263-3), then
      extensively screened a series of additional MORs related to MOR263-3 in various
      ways. MORs related by phylogenetic analysis had odorant specificities that
      overlapped with that of MOR263-3, but MOR171-17, predicted to be functionally
      related to MOR263-3 by an alternative bioinformatic analysis, had a distinct
      odorant specificity. 

PMID- 25772783
TI  - Assessing pain objectively: the use of physiological markers.
AB  - Pain diagnosis and management would benefit from the development of objective
      markers of nociception and pain. Current research addressing this issue has
      focused on five main strategies, each with its own advantages and disadvantages.
      These encompass: (i) monitoring changes in the autonomic nervous system; (ii)
      biopotentials; (iii) neuroimaging; (iv) biological (bio-) markers; and (v)
      composite algorithms. Although each strategy has shown areas of promise, there
      are currently no validated objective markers of nociception or pain that can be
      recommended for clinical use. This article introduces the most important
      developments in the field and highlights shortcomings, with the aim of allowing
      the reader to make informed decisions about what trends to watch in the future.

PMID- 25772784
TI  - The formaldehyde dilemma.
AB  - The IARC's 2004 classification of formaldehyde as a human carcinogen has led to
      intensive discussion on scientific and regulatory levels. In June 2014, the
      European Union followed and classified formaldehyde as a cause of cancer. This
      automatically triggers consequences in terms of emission minimization and the
      health-related assessment of building and consumer products. On the other hand,
      authorities are demanding and authorizing technologies and products which can
      release significant quantities of formaldehyde into the atmosphere. In the
      outdoor environment, this particularly applies to combusting fuels. The formation
      of formaldehyde through photochemical smog has also been a recognized problem for
      years. Indoors there are various processes which can contribute to increased
      formaldehyde concentrations. Overall, legislation faces a dilemma: primary
      sources are often over-regulated while a lack of consideration of secondary
      sources negates the regulations' effects. 

PMID- 25772785
TI  - Persistent high mortality in advanced HIV/TB despite appropriate antiretroviral
      and antitubercular therapy: an emerging challenge.
AB  - Approximately 1.1 million, or 13 %, of all TB cases in 2013 were coinfected with
      HIV, and in some African countries, such as Botswana and Swaziland, 60-80 % of TB
      cases are coinfected with HIV. Effective therapies for both HIV and TB exist, yet
      patients presenting with TB and advanced HIV still experience high rates of
      morbidity and mortality despite initiation of both antitubercular and
      antiretroviral therapy (ART). Previous reviews and research have focused largely
      on TB-associated immune reconstitution inflammatory syndrome (TB-IRIS) as a type
      of complicated outcome on ART in advanced HIV/TB, but recent data indicate that
      immunologic failure despite suppressive ART is associated with early mortality.
      In this review, we examine recent findings regarding early mortality in HIV/TB
      and emerging concepts in the pathophysiology of TB-IRIS, in order to provide an
      integrated view of factors determining outcomes in coinfected people as well as
      highlight key needs for future research and therapeutic development. 

PMID- 25772786
TI  - Serotonergic genes and depressive disorder in acute coronary syndrome: The Korean
      depression in ACS (K-DEPACS) study.
AB  - Genes coding for the serotonergic pathway have been associated with depressive
      disorders. However, these associations have rarely been tested in acute coronary
      syndrome (ACS) patients vulnerable to depression. This study aimed to investigate
      whether polymorphisms of serotonin transporter (5-HTT) and serotonin 2a receptor
      (5-HTR2a) genes are associated with occurrence of depressive disorder in ACS. 969
      patients with recently developed ACS were recruited at baseline, and 711 were
      followed 1 year thereafter. Depressive disorder was diagnosed according to DSM-IV
      criteria, and analysed as an outcome at baseline (prevalence), and follow up
      (incidence and persistence). Genotypes were ascertained for 5-HTTLPR, STin2 VNTR,
      5-HTR2a 102T/C, and 5-HTR2a 1438A/G. Logistic regression models were used to
      investigate associations. The 5-HTTLPR s/s genotype was independently associated
      with depressive disorder prevalence and persistence following ACS, but no
      significant associations were found with the other polymorphisms. ACS patients
      with the 5-HTTLPR s allele are thus potentially susceptible to depressive
      disorder in the early phase after ACS, and with its persistence over the
      subsequent year. 

PMID- 25772788
TI  - N170 adaptation effect for repeated faces and words.
AB  - Using ERP adaptation paradigms, studies have shown that the N170 adaptation
      effect is a stable phenomenon for both faces and words. However, the N170
      adaptation effect for repeated identity remains unclear, so we have addressed
      this with two experiments. In Experiment 1, we investigated the face-related N170
      repeated adaptation effect in a short interstimulus interval (ISI) and found that
      the N170 response elicited by faces was smaller when preceded by a same face
      adaptor than by another face adaptor. Experiment 2 addressed whether this
      repeated N170 adaptation effect generalizes to words. For the first time, the
      results indicated that the N170 response elicited by words was larger with a
      different word as an adaptor relative to the same word as an adaptor. Our results
      demonstrate that the face-related N170 response is sensitive to visual face
      features and extend the characteristics of N170 with the sensitivity to repeated
      items to other familiar objects of expertise (i.e. words). The results also
      suggest that there are some common characteristics between faces and words in the
      early perceptual processing.

PMID- 25772790
TI  - Cloning and serotonergic regulation of RING finger protein38 (rnf38) in the brain
      of medaka (Oryzias latipes).
AB  - Serotonin (5-HT) is a key regulator of mood and sexual behaviors. 5-HT reuptake
      inhibitors have been used as antidepressants. Really interesting new gene (RING)
      finger proteins have been associated with 5-HT regulation but their role remains
      largely unknown. Some RING finger proteins are involved in the serotonergic
      system, therefore, we speculate that the gene expression of RING finger protein38
      (rnf38) is regulated by the serotonergic system. In the present study, we aimed
      to identify the full length sequence of medaka (Oryzias latipes) rnf38 mRNA and
      investigate its association with the serotonergic system using an antidepressant,
      citalopram (CIT). We identified the full length rnf38 cDNA, which consisted of
      2726 nucleotides spanning 12 exons and the deduced protein sequence consisting of
      518 amino acid residues including a RING finger domain, a KIT motif and a coiled
      coil domain. Medaka exposed to 10(-7)M of CIT showed anxiety-like behavior. The
      expressions of 5-HT-related genes, pet1, solute carrier family 6, member 4A
      (slc6a4) and tryptophan hydroxylase (tph2) were significantly low (P<0.05) in the
      hindbrain. On the other hand, rnf38 gene was significantly high (P<0.05) in the
      telencephalon and the hypothalamus. This shows that 5-HT synthesis and transport
      in the hindbrain is suppressed by CIT, which induces rnf38 gene expression in the
      forebrain where 5-HT neurons project. Thus, the expression of rnf38 is negatively
      regulated by the serotonergic system.

PMID- 25772787
TI  - Hippocampal plasticity during the progression of Alzheimer's disease.
AB  - Neuroplasticity involves molecular and structural changes in central nervous
      system (CNS) throughout life. The concept of neural organization allows for
      remodeling as a compensatory mechanism to the early pathobiology of Alzheimer's
      disease (AD) in an attempt to maintain brain function and cognition during the
      onset of dementia. The hippocampus, a crucial component of the medial temporal
      lobe memory circuit, is affected early in AD and displays synaptic and
      intraneuronal molecular remodeling against a pathological background of
      extracellular amyloid-beta (Abeta) deposition and intracellular neurofibrillary
      tangle (NFT) formation in the early stages of AD. Here we discuss human clinical
      pathological findings supporting the concept that the hippocampus is capable of
      neural plasticity during mild cognitive impairment (MCI), a prodromal stage of AD
      and early stage AD. 

PMID- 25772791
TI  - Immunohistochemical determination of the site of antidepressant-like effects of
      glucagon-like peptide-2 in ACTH-treated mice.
AB  - The intracerebroventicular administration (i.c.v.) of glucagon-like peptide-2
      (GLP-2) had antidepressant-like effects on saline-treated mice in the forced-swim
      test. The GLP-2 treatment (3 MUg, i.c.v.) for 6 days, but not that of imipramine
      had antidepressant-like effects on adrenocorticotropic hormone (ACTH)-treated
      mice. The immunohistochemical detection of the c-fos protein (Fos) revealed that
      the administration of GLP-2 induced Fos-immunoreactivity (Fos-IR) in the
      dorsomedial hypothalamic nucleus in saline-treated and ACTH-treated mice, and
      also in the hippocampal dentate gyrus in ACTH-treated mice, but not in saline
      treated mice. In contrast, Fos-IR in the paraventricular nucleus of the
      hypothalamus decreased after the administration of GLP-2 to ACTH-treated mice. In
      ACTH-treated mice, the chronic administration of GLP-2 affected hippocampal
      neurogenesis, in addition to Fos-IR in hypothalamic GABAergic neurons and
      corticotrophin-releasing factor-containing neurons. These results suggest that
      GLP-2 acts on specific brain regions to regulate stress conditions, and induces
      antidepressant-like effects under imipramine-resistant conditions, which may be
      associated with the modulation of the hypothalamic-pituitary-adrenal-axis.

PMID- 25772792
TI  - Preserved motor asymmetry in late adulthood: is measuring chronological age
      enough?
AB  - When comparing motor performance of the dominant and nondominant hands, older
      adults tend to be less asymmetric compared to young adults. This has suggested
      decreased motor lateralization and functional compensation within the aging
      brain. The current study further addressed this question by testing whether motor
      asymmetry was reduced in a sample of 44 healthy right-handed adults ages 65-89.
      We hypothesized that the older the age, the less the motor asymmetry, and that
      'old old' participants (age 80+) would have less motor asymmetry than 'young old'
      participants (age 65-79). Using two naturalistic tasks that selectively biased
      the dominant or nondominant hands, we compared asymmetries in performance
      (measured as a ratio) across chronological age. Results showed preserved motor
      asymmetry across ages in both tasks, with no difference in asymmetry ratios in
      the 'old old' compared to the 'young old.' In the context of previous work, our
      findings suggest that the aging brain may also be characterized by additional
      measures besides chronological age.

PMID- 25772793
TI  - Drug safety evaluation of ulipristal acetate in the treatment of uterine
      fibroids.
AB  - INTRODUCTION: Ulipristal acetate (UPA) is a selective progesterone-receptor
      modulator (SPRM). SPRMs are a new class of progesterone-receptor ligands that
      exert tissue selective agonist, antagonist or mixed agonist-antagonist activity
      in target cells. UPA inhibits the proliferation, induces apoptosis of leiomyoma
      cells in vitro and demonstrates potent progesterone antagonist activity in vitro
      and in vivo. AREAS COVERED: This manuscript aims to review the available data on
      safety of UPA in the treatment of uterine fibroids. Data and articles included in
      this manuscript were obtained via PubMed, Medline and Embase up to November 2014.
      EXPERT OPINION: UPA is efficacious in the treatment of uterine fibroids before
      surgery; it decreases leiomyoma volume and uterine bleeding; furthermore, it
      improves quality of life. Short-term administration of UPA has been shown to be
      safe at short follow-up (months) and it is associated with minimal adverse side
      effects; further studies with longer follow-up are required to define the safety
      profile of UPA on endometrial histology.

PMID- 25772789
TI  - Neuroinflammation in the normal aging hippocampus.
AB  - A consequence of normal aging is a greater susceptibility to memory impairments
      following an immune challenge such as infection, surgery, or traumatic brain
      injury. The neuroinflammatory response, produced by these challenges results in
      increased and prolonged production of pro-inflammatory cytokines in the otherwise
      healthy aged brain. Here we discuss the mechanisms by which long-lasting
      elevations in pro-inflammatory cytokines in the hippocampus produce memory
      impairments. Sensitized microglia are a primary source of this exaggerated
      neuroinflammatory response and appear to be a hallmark of the normal aging brain.
      We review the current understanding of the causes and effects of normal aging
      induced microglial sensitization, including dysregulations of the neuroendocrine
      system, potentiation of neuroinflammatory responses following an immune
      challenge, and the impairment of memories. We end with a discussion of
      therapeutic approaches to prevent these deleterious effects. 

PMID- 25772795
TI  - Mixed quantum-classical dynamics for charge transport in organics.
AB  - Charge transport plays a crucial role in the working principle of most opto
      electronic and energy devices. This is especially true for organic materials
      where the first theoretical models date back to the 1950s and have continuously
      evolved ever since. Most of these descriptions rely on perturbation theory to
      treat small interactions in the Hamiltonian. In particular, applying a
      perturbative treatment to the electron-phonon and electron-electron coupling
      results in the band and hopping models, respectively, the signature of which is
      conveyed by a characteristic temperature dependence of mobility. This perspective
      describes recent progress of studying charge transport in organics using mixed
      quantum-classical dynamics techniques, including mean field and surface hopping
      theories. The studies go beyond the perturbation treatments and represent the
      processes explicitly in the time-domain, as they occur in real life. The
      challenges, advantages, and disadvantages of both approaches are systematically
      discussed. Special focus is dedicated to the temperature dependence of mobility,
      the role of local and nonlocal electron-phonon couplings, as well as the
      interplay between electronic and electron-phonon interactions. 

PMID- 25772794
TI  - IL-4 Knock Out Mice Display Anxiety-Like Behavior.
AB  - Inflammation is a recognized antecedent and coincident factor when examining the
      biology of anxiety. Little is known, however, about how reductions in endogenous
      anti-inflammatory mediators impact anxiety. Therefore, mood- cognition- and
      anxiety-associated/like behaviors were examined in IL-4 knock out (KO) mice and
      wild-type (WT) mice. In comparison to WT mice, IL-4 KO mice demonstrated
      decreased burrowing and increased social exploration. No differences were seen in
      forced swim or saccharine preference testing. IL-4 KO mice had similar
      performance to WT mice in the Morris water maze and during object location and
      novel object recognition. In the elevated zero-maze, IL-4 KO mice, in comparison
      to WT mice, demonstrated anxiety-like behavior. Anxiety-like behavior in IL-4 KO
      mice was not observed, however, during open-field testing. Taken together, these
      data indicate that IL-4 KO mice display state, but not trait, anxiety suggesting
      that reductions in endogenous anti-inflammatory bioactives can engender subtypes
      of anxiety. 

PMID- 25772797
TI  - A systematic review of the literature on the surgical management of recurrent
      rectal prolapse.
AB  - AIM: There are no available guidelines to support surgical decision-making in
      recurrent rectal prolapse. This systematic review evaluated the results of
      abdominal or perineal surgery for recurrent rectal prolapse, with the aim of
      developing an evidence-based treatment algorithm. METHOD: PubMed and MEDLINE
      databases were searched for all clinical studies involving patients who underwent
      surgery for recurrent rectal prolapse between 1950 and 2014. The primary outcome
      measure was the recurrence rate after abdominal or perineal surgery for recurrent
      rectal prolapse. Secondary outcomes included morbidity, mortality and quality of
      life data where available. RESULTS: There were no randomized controlled studies
      comparing the success rates of abdominal or perineal surgery for recurrent rectal
      prolapse. Most studies were heterogeneous, of low quality (level IV) and involved
      small numbers of patients. The follow-up of 144 patients included in the studies
      undergoing perineal surgery ranged from 8.8 to 81 months, with recurrence rates
      varying from 0% to 50%. Morbidity ranged from 0% to 17% with no mortality
      reported. Limited data on quality of life following the Altemeier procedure were
      available. The follow-up for 158 patients included in the studies who underwent
      abdominal surgery ranged from 0 to 23 years, during which recurrence rates varied
      from 0% to 15%. Morbidity rates ranged from 0% to 32% with 4% mortality. No
      quality of life data were available for patients undergoing abdominal surgery.
      CONCLUSION: This systematic review was unable to develop a treatment algorithm
      for recurrent rectal prolapse due to the variety of surgical techniques described
      and the low level of evidence within heterogeneous studies. Larger high-quality
      studies are necessary to guide practice in this difficult area.

PMID- 25772796
TI  - Decision aids for localized prostate cancer treatment choice: Systematic review
      and meta-analysis.
AB  - Patients who are diagnosed with localized prostate cancer need to make critical
      treatment decisions that are sensitive to their values and preferences. The role
      of decision aids in facilitating these decisions is unknown. The authors
      conducted a systematic review of randomized trials of decision aids for localized
      prostate cancer. Teams of 2 reviewers independently identified, selected, and
      abstracted data from 14 eligible trials (n = 3377 men), of which 10 were
      conducted in North America. Of these, 11 trials compared decision aids with usual
      care, and 3 trials compared decision aids with other decision aids. Two trials
      suggested a modest positive impact on decisional regret. Results across studies
      varied widely for decisional conflict (4 studies), satisfaction with decision (2
      studies), and knowledge (2 studies). No impact on treatment choices was observed
      (6 studies). In conclusion, scant evidence at high risk of bias suggests the
      variable impact of existing decision aids on a limited set of decisional
      processes and outcomes. Because current decision aids provide information but do
      not directly facilitate shared decision making, subsequent efforts would benefit
      from user-centered design of decision aids that promote shared decision making.

PMID- 25772798
TI  - Neoadjuvant chemotherapy for primary cutaneous/soft tissue angiosarcoma:
      Determining tumor behavior prior to surgical resection.
AB  - BACKGROUND: Given the propensity for hematogenous metastases, neoadjuvant
      chemotherapy (NAC) could treat occult metastatic disease early, potentially
      improving survival and better defining which primary angiosarcomas (AS) benefit
      from surgical resection. METHODS: A retrospective comparison was performed of 23
      patients with resectable, localized cutaneous/soft tissue primary AS treated with
      surgery alone (S, n = 13) or NAC followed by surgery (NAC-S, n = 12). RESULTS:
      Primary sites included breast/chest (n = 9), head/neck (n = 9), extremity (n =
      3), and other (n = 2). 23% S versus 40% NAC-S had prior radiation (RT). NAC
      regimens were paclitaxel (n = 6) or gemcitabine/docetaxel (n = 4). Seventy
      percent were high grade. Distant metastases were found in 17% after NAC. Non
      primary wound closure was required in 54 %S versus 30%NAC-S (P = 0.4). R0
      resections were achieved in 85% S versus 80% NAC-S (30% had a complete pathologic
      response). Two-year local recurrence (LR)-free, disease-free, and overall
      survivals were 67.1, 38.5, and 61.5% for S versus 68.6, 54.9, and 68.6% for NAC-S
      (P = 0.52, 0.67, and 0.58). The mean number of surgical resections/patient to
      maintain local control was 1.8 S versus 1.3 NAC-S (P = 0.06). CONCLUSIONS: NAC
      for primary AS was well tolerated. Although there was no statistically
      significant survival benefit, NAC helped define who would benefit from surgical
      resection.

PMID- 25772800
TI  - Multilocus phylogenetic analyses of Hispaniolan and Bahamian trunk anoles
      (distichus species group).
AB  - The distichus species group includes six species and 21 subspecies of trunk
      ecomorph anoles distributed across Hispaniola and its satellite islands as well
      as the northern Bahamas. Although this group has long served as a model system
      for studies of reproductive character displacement, adaptation, behavior and
      speciation, it has never been the subject of a comprehensive phylogenetic
      analysis. Our goal here is to generate a multilocus phylogenetic dataset (one
      mitochondrial and seven nuclear loci) and to use this dataset to infer
      phylogenetic relationships among the majority of the taxa assigned to the
      distichus species group. We use these phylogenetic trees to address three topics
      about the group's evolution. First, we consider longstanding taxonomic
      controversies about the status of several species and subspecies assigned to the
      distichus species group. Second, we investigate the biogeographic history of the
      group and specifically test the hypotheses that historical division of Hispaniola
      into two paleo-islands contributed to the group's diversification and that
      Bahamian and Hispaniolan satellite island populations are derived from colonists
      from the main Hispaniolan landmass. Finally, third, we use comparative
      phylogenetic analyses to test the hypothesis that divergence between pale yellow
      and darkly pigmented orange or red dewlap coloration has occurred repeatedly
      across the distichus species group. 

PMID- 25772801
TI  - The role of temozolomide in the treatment of aggressive pituitary tumors.
AB  - Pituitary tumors are amongst the most common intracranial neoplasms and are
      generally benign. However, some pituitary tumors exhibit clinically aggressive
      behavior that is characterized by tumor recurrence and continued progression
      despite repeated treatments with conventional surgical, radiation and medical
      therapies. More recently, temozolomide, a second generation oral alkylating
      agent, has shown therapeutic promise for aggressive pituitary adenomas and
      carcinomas with favorable clinical and radiographic responses. Temozolomide
      causes DNA damage by methylation of the O(6) position of guanine, which results
      in potent cytotoxic DNA adducts and consequently, tumor cell apoptosis. The
      degree of MGMT expression appears to be inversely related to therapeutic
      responsiveness to temozolomide with a significant number of temozolomide
      sensitive pituitary tumors exhibiting low MGMT expression. The presence of high
      MGMT expression appears to mitigate the effectiveness of temozolomide and this
      has been used as a marker in several studies to predict the efficacy of
      temozolomide. Recent evidence also suggests that mutations in mismatch repair
      proteins such as MSH6 could render pituitary tumors resistant to temozolomide. In
      this article, the authors review the development of temozolomide, its
      biochemistry and interaction with O(6)-methylguanine-DNA methyltransferase
      (MGMT), its role in adjuvant treatment of aggressive pituitary neoplasms, and
      future works that could influence the efficacy of temozolomide therapy. 

PMID- 25772799
TI  - Multi-locus tree and species tree approaches toward resolving a complex clade of
      downy mildews (Straminipila, Oomycota), including pathogens of beet and spinach.
AB  - Accurate species determination of plant pathogens is a prerequisite for their
      control and quarantine, and further for assessing their potential threat to
      crops. The family Peronosporaceae (Straminipila; Oomycota) consists of obligate
      biotrophic pathogens that cause downy mildew disease on angiosperms, including a
      large number of cultivated plants. In the largest downy mildew genus Peronospora,
      a phylogenetically complex clade includes the economically important downy mildew
      pathogens of spinach and beet, as well as the type species of the genus
      Peronospora. To resolve this complex clade at the species level and to infer
      evolutionary relationships among them, we used multi-locus phylogenetic analysis
      and species tree estimation. Both approaches discriminated all nine currently
      accepted species and revealed four previously unrecognized lineages, which are
      specific to a host genus or species. This is in line with a narrow species
      concept, i.e. that a downy mildew species is associated with only a particular
      host plant genus or species. Instead of applying the dubious name Peronospora
      farinosa, which has been proposed for formal rejection, our results provide
      strong evidence that Peronospora schachtii is an independent species from
      lineages on Atriplex and apparently occurs exclusively on Beta vulgaris. The
      members of the clade investigated, the Peronospora rumicis clade, associate with
      three different host plant families, Amaranthaceae, Caryophyllaceae, and
      Polygonaceae, suggesting that they may have speciated following at least two
      recent inter-family host shifts, rather than contemporary cospeciation with the
      host plants. 

PMID- 25772802
TI  - Chorea associated with nonketotic hyperglycemia: An uncommon patient with
      bilateral movements.
AB  - We report a 74-year-old woman who presented with bilateral chorea and no known
      history of diabetes. Movement disorders such as chorea can be observed in
      patients presenting with hyperglycemia. The occurrence of hemichorea-hemiballism
      has been increasingly associated with nonketotic hyperglycemia in the medical
      literature. The chorea disappeared completely after correction of the
      hyperglycemia. 

PMID- 25772803
TI  - Febrile Hashimoto's encephalopathy associated with Hashitoxicosis.

PMID- 25772804
TI  - De novo R853Q mutation of SCN2A gene and West syndrome.

PMID- 25772805
TI  - Fibrillarin from Archaea to human.
AB  - Fibrillarin is an essential protein that is well known as a molecular marker of
      transcriptionally active RNA polymerase I. Fibrillarin methyltransferase activity
      is the primary known source of methylation for more than 100 methylated sites
      involved in the first steps of preribosomal processing and required for
      structural ribosome stability. High expression levels of fibrillarin have been
      observed in several types of cancer cells, particularly when p53 levels are
      reduced, because p53 is a direct negative regulator of fibrillarin transcription.
      Here, we show fibrillarin domain conservation, structure and interacting
      molecules in different cellular processes as well as with several viral proteins
      during virus infection. 

PMID- 25772806
TI  - Low-Load Very High-Repetition Resistance Training Attenuates Bone Loss at the
      Lumbar Spine in Active Post-menopausal Women.
AB  - This study determined the effect of 6 months of low-load very high-repetition
      resistance training on bone mineral density (BMD) and body composition in
      nonosteoporotic middle-aged and older women. Fifty healthy, active community
      dwelling women aged 56-75 years took part in the two-group, repeated-measures
      randomized controlled trial. Participants either undertook 6 months of low-load
      very high-repetition resistance training in the form of BodyPumpTM or served as
      control participants. Outcome measures included BMD at the lumbar spine, hip, and
      total body; total fat mass; fat-free soft tissue mass and maximal isotonic
      strength. Significant group-by-time interactions were found for lumbar spine BMD
      and maximal strength in favor of the BodyPumpTM group. No favorable effects were
      found for hip BMD, total body BMD, total fat mass, or fat-free soft tissue mass.
      Three participants withdrew from the intervention group due to injury or fear of
      injury associated with training. Under the conditions used in this research, low
      load very high-repetition resistance training is effective at attenuating losses
      in lumbar spine BMD compared to controls in healthy, active women aged over 55
      years but did not influence hip and total body BMD or fat mass and fat-free soft
      tissue mass.

PMID- 25772808
TI  - Erratum to: Thyroid Hormone Attenuates Vascular Calcification Induced by Vitamin
      D3 Plus Nicotine in Rats.

PMID- 25772809
TI  - How to choose a precursor for decomposition solution-phase synthesis: the case of
      iron nanoparticles.
AB  - The decomposition of organometallic compounds as precursors has revolutionized
      the synthesis of nanoparticles in solution. However, effective control of size
      and size distribution of iron nanoparticles has remained challenging due to the
      high reactivity of iron towards oxygen or oxygen-containing materials. Reported
      is a decomposition study that shows how metal to ligand bonding and symmetry of
      the compound can be manipulated to control the size and size distribution of iron
      nanoparticles in the 6-16 nm range. [Fe(eta(5)-C6H3Me4)2] was found to be the
      optimal precursor with a narrow decomposition temperature range due to its
      symmetry and the low bond dissociation energy of the ligands from the Fe(ii)
      center. The precise control of nanoparticle size has enabled the tuning of
      magnetic properties from superparamagnetic to soft-ferromagnetic desirable for a
      wide range of biomedical applications. 

PMID- 25772807
TI  - Fragility of Bone Material Controlled by Internal Interfaces.
AB  - Bone material is built in a complex multiscale arrangement of mineralized
      collagen fibrils containing water, proteoglycans and some noncollagenous
      proteins. This organization is not static as bone is constantly remodeled and
      thus able to repair damaged tissue and adapt to the loading situation. In
      preventing fractures, the most important mechanical property is toughness, which
      is the ability to absorb impact energy without reaching complete failure. There
      is no simple explanation for the origin of the toughness of bone material, and
      this property depends in a complex way on the internal architecture of the
      material on all scales from nanometers to millimeters. Hence, fragility may have
      different mechanical origins, depending on which toughening mechanism is not
      working properly. This article reviews the toughening mechanisms described for
      bone material and attempts to put them in a clinical context, with the hope that
      future analysis of bone fragility may be guided by this collection of possible
      mechanistic origins. 

PMID- 25772810
TI  - NMR artifacts caused by decoupling of multiple-spin coherences: improved SLAP
      experiment.
AB  - Contrary to common expectations, multiple-spin coherences containing products of
      proton and heteronucleus operators (e.g. Hu Cx , u = x, y, z) can produce not
      only sidebands but also noticeable centerband NMR signals of the heteronucleus
      during acquisition under 1H broadband decoupling. Such centerband signals of low
      abundant heteronuclei can be sources of relatively strong unexpected artifacts in
      NMR experiments that aim to detect very weak signals from much less-abundant
      isotopomers, e.g. 13C-13C ones. These findings lead to a new design of Sign
      Labeled Polarization Transfer (SLAP) pulse sequence (MSS-SLAP) with improved
      suppression of centerband peaks that are because of singly, e.g. 13C, labeled
      molecules (parent peaks). The MSS-SLAP experiment and its MSS-BIRD-SLAP variant
      are compared with a few older SLAP versions.

PMID- 25772811
TI  - Coronary Artery Spasm During Cryothermal Cavotricuspid Isthmus Ablation.

PMID- 25772812
TI  - Prevalence of conditions causing chronic anovulation and the proposed algorithm
      for anovulation evaluation.
AB  - AIM: This study investigated the prevalence of disease-causing chronic
      anovulation and proposes a logical investigation flowchart to facilitate
      diagnosis in women presenting with chronic anovulation. MATERIAL AND METHODS: The
      cross-sectional retrospective study was performed using 293 reproductive-aged
      women who were diagnosed with chronic anovulation at the Gynecologic
      Endocrinology Unit, Faculty of Medicine, Chiang Mai University between January
      2008 and December 2012. The demographic data, laboratory investigations and
      diagnoses were collected. RESULTS: Among 293 patients recruited into the study,
      the common causes of anovulation were polycystic ovary syndrome (PCOS) (73.4%),
      prolactin disorder (13.3%) and unexplained chronic anovulation (7.5%). The less
      common causes were thyroid disorders, congenital adrenal hyperplasia, adrenal
      tumors and Cushing's disease. There was a strong positive association between the
      levels of 17-hydroxyprogesterone and/or dehydroepiandrosterone sulfate with the
      levels of testosterone and androstenedione. The sensitivity and specificity of
      serum luteinizing hormone to accurately diagnose PCOS were 29.38% and 55.56% (P =
      0.03). The luteinizing hormone/follicle-stimulating hormone ratio >= 3 had a
      sensitivity and specificity at 18.56% and 92.86% (P = 0.03) for PCOS diagnosis.
      CONCLUSION: Serum androstenedione, testosterone, thyroid-stimulating hormone,
      prolactin levels and pelvic ultrasonography should be included in the initial
      investigations for anovulation. The 17-hydroxyprogesterone and
      dehydroepiandrosterone sulfate levels can be used for secondary anovulation
      evaluations.

PMID- 25772813
TI  - Anomalous transport of impurities in inelastic Maxwell gases.
AB  - A mixture of dissipative hard grains generically exhibits a breakdown of kinetic
      energy equipartition. The undriven and thus freely cooling binary problem, in the
      tracer limit where the density of one species becomes minute, may exhibit an
      extreme form of this breakdown, with the minority species carrying a finite
      fraction of the total kinetic energy of the system. We investigate the
      fingerprint of this non-equilibrium phase transition, akin to an ordering
      process, on transport properties. The analysis, performed by solving the
      Boltzmann kinetic equation from a combination of analytical and Monte Carlo
      techniques, hints at the possible failure of hydrodynamics in the ordered region.
      As a relevant byproduct of the study, the behaviour of the second- and fourth
      degree velocity moments is also worked out. 

PMID- 25772814
TI  - Amino acid challenge and depletion techniques in human functional neuroimaging
      studies: an overview.
AB  - Imbalances of neurotransmitter systems, particularly serotonin (5-HT) and
      dopamine (DA), are known to play an essential role in many neuropsychiatric
      disorders. The transient manipulation of such systems through the alteration of
      their amino acid precursors is a well-known research tool. Among these methods
      are alterations of tryptophan, the essential amino acid (AA) precursor of 5-HT,
      as well as manipulations of tyrosine and phenylalanine, the AA precursors of DA,
      which can be metabolized into norepinephrine and subsequently into epinephrine.
      These systems can be loaded by applying a large dose of these AAs or depleted by
      applying an amino acid mixture lacking the respective AAs serving as precursors.
      Functional neuroimaging has given insights into differential brain activation
      patterns and functions depending on the tasks performed, pharmacological
      treatments or specific disorders. Such research has shed light on the function of
      many brain areas as well as their interactions. The combination of AA challenge
      approaches with neuroimaging techniques has been subject of numerous studies.
      Overall, the studies conducted in this particular field of research have shown
      that AA challenge techniques are valid and effective research tools that allow
      the investigation of serotonergic and dopaminergic systems without causing
      serious side effects or long-term damage to the subjects. In this review, we will
      present an overview of the results obtained so far and discuss the implications
      of these findings as well as open questions that remain to be answered. 

PMID- 25772815
TI  - Leucine-enriched essential amino acids attenuate muscle soreness and improve
      muscle protein synthesis after eccentric contractions in rats.
AB  - Eccentric exercise results in prolonged muscle weakness and muscle soreness,
      which are typical symptoms of muscle damage. Recovery from muscle damage is
      related to mammalian target of rapamycin (mTOR) activity. Leucine-enriched
      essential amino acids (LEAAs) stimulate muscle protein synthesis via activation
      of the mTOR pathway. Therefore, we investigated the effect of LEAAs on muscle
      protein synthesis and muscle soreness after eccentric contractions (EC). Male
      Sprague-Dawley rats (9-11 weeks old) were administered an LEAA solution
      (AminoL40; containing 40 % leucine and 60 % other essential amino acids) at 1
      g/kg body weight or distilled water (control) 30 min before and 10 min after EC.
      Tibialis anterior (TA) muscle was exposed to 500 EC by electrical stimulation
      under anesthesia. The fractional synthesis rate (FSR; %/h) in the TA muscle was
      measured by incorporating L-[ring-(2)H5] phenylalanine into skeletal muscle
      protein. Muscle soreness was evaluated by the paw withdrawal threshold using the
      Randal-Selitto test with some modifications from 1 to 3 days after EC. The FSR in
      the EC-control group (0.147 +/- 0.016 %/h) was significantly lower than in the
      sedentary group (0.188 +/- 0.016 %/h, p < 0.05). AminoL40 administration
      significantly mitigated the EC-induced impairment of the FSR (0.172 +/- 0.018
      %/h). EC decreased the paw withdrawal threshold at 1 and 2 days after EC, which
      indicated that EC induced muscle soreness. Furthermore, AminoL40 administration
      alleviated the decreased paw withdrawal threshold. These findings suggest that
      LEAA supplementation improves the rate of muscle protein synthesis and
      ameliorates muscle soreness after eccentric exercise.

PMID- 25772816
TI  - Propargylglycine inhibits hypotaurine/taurine synthesis and elevates
      cystathionine and homocysteine concentrations in primary mouse hepatocytes.
AB  - Our investigation showed that hepatocytes isolated from cysteine dioxygenase
      knockout mice (Cdo1(-/-)) had lower levels of hypotaurine and taurine than Cdo1
      (+/+) hepatocytes. Interestingly, hypotaurine accumulates in cultured wild-type
      hepatocytes. DL-propargylglycine (PPG, inhibitor of cystathionine gamma-lyase and
      H2S production) dramatically decreased both taurine and hypotaurine levels in
      wild-type hepatocytes compared to untreated cells. Addition of 2 mM PPG resulted
      in the decrease of the intracellular taurine levels: from 10.25 +/- 5.00 observed
      in control, to 2.53 +/- 0.68 nmol/mg protein (24 h of culture) and from 17.06 +/-
      9.40 to 2.43 +/- 0.26 nmol/mg protein (control vs. PPG; 48 h). Addition of PPG
      reduced also intracellular hypotaurine levels: from 7.46 +/- 3.55 to 0.31 +/-
      0.12 nmol/mg protein (control vs. PPG; 24 h) and from 4.54 +/- 3.20 to 0.42 +/-
      0.11 nmol/mg protein (control vs. PPG; 48 h). The similar effects of PPG on
      hypotaurine and taurine levels were observed in culture medium. PPG blocked
      hypotaurine/taurine synthesis in wild-type hepatocytes, suggesting that it
      strongly inhibits cysteinesulfinate decarboxylase (pyridoxal 5'-phosphate
      dependent enzyme) as well as cystathionine gamma-lyase. In the presence of PPG,
      intracellular and medium cystathionine levels for both wild-type and Cdo1 (-/-)
      cells were increased. Addition of homocysteine or methionine resulted in higher
      intracellular concentrations of homocysteine, which is a cosubstrate for
      cystathionine beta-synthase (CBS). It seems that PPG increases CBS-mediated
      desulfhydration by enhancing homocysteine levels in hepatocytes. There were no
      overall effects of PPG or genotype on intracellular or medium glutathione levels.

PMID- 25772817
TI  - Symmetric dimethylarginine (SDMA) serum levels in rheumatoid arthritis:
      correlations with insulin resistance and disease activity scores.
AB  - Vascular abnormalities predisposing to atherosclerosis are present in patients
      with rheumatoid arthritis (RA) and associate with excess cardiovascular risk.
      Symmetric dimethylarginine (SDMA), an endogenous inhibitor of nitric oxide (NO)
      synthase activity, has been recognised as novel risk factor for endothelial
      dysfunction and cardiovascular disease. We aimed to compare SDMA levels in RA
      patients and controls and to investigate whether they are influenced by
      demographic, inflammatory or metabolic factors. Serum SDMA levels were measured
      in 197 RA individuals [median age: 67 years (quartiles: 59-3), 153 (78 %)
      females] and 82 controls [median age: 44 years [quartiles: 33-55, 50 (61 %)
      females]. Routine biochemistry tests, lipid profile, glycemic profile [glucose,
      insulin, homeostasis model assessment (HOMA-IR), quantitative insulin sensitivity
      check index (QUICKI)], as well as inflammatory markers were measured in all
      patients. Paired analysis was employed for the comparison of SDMA in two groups
      and multivariable regression models were performed to identify predictors of SDMA
      in the RA cohort. SDMA was significantly lower in RA than control patients in
      both unpaired and paired analyses (P < 0.001 and P = 0.005, respectively), with
      the magnitude of the difference being similar in both models. QUICKI (P = 0.005)
      and disease activity score-28 (P = 0.007) were positively related to SDMA in the
      RA cohort, whilst a negative correlation with renal function (eGFR) was detected
      (P = 0.005). The molecular explanation of lower serum SDMA is unclear, but the
      established relationships with indices of disease activity and insulin
      resistance, may underline the pathogenetic role of the L-arginine/NO pathway
      dysregulation in the development of atherosclerosis in RA. The biological and
      clinical importance of SDMA in RA remains to be evaluated in clinical and
      experimental studies.

PMID- 25772818
TI  - Structure-based development and optimization of therapy antibody drugs against
      TNFalpha.
AB  - Previously, we reported on the crystal structures of the Fab fragments of two
      food and drug administration approved therapeutic antibodies, Infliximab and
      Adalimumab, in complex with TNFalpha. The structurally identified epitopes on
      TNFalpha reveal the mechanism of TNFalpha inhibition by partially overlapping
      with the TNFalpha-receptor interface. In this study, we launched a screen of a
      phage display library to isolate novel anti-TNFalpha antibodies based on the
      adalimumab epitope. Structural analysis, the phage display antibody isolation
      technology, step-by-step antibody optimization, complementarity-determining
      region residues random mutagenesis, phage ELISA, binding affinity
      characterization, and cell signaling assays were used for the development and
      optimization of the novel anti-TNFalpha antibodies. Moreover, one of the novel
      antibodies, hAta09, has a superior inhibitory effect on TNFalpha function and
      signaling. Taken together, our report established that the novel anti-TNFalpha
      antibody hAta09 may achieve clinical efficacy in a TNFalpha-associated disease. 

PMID- 25772819
TI  - Contact bubble bilayers with flush drainage.
AB  - Planar lipid bilayers have been used to form stable bilayers into which membrane
      proteins are reconstituted for measurements of their function under an applied
      membrane potential. Recently, a lipid bilayer membrane is formed by the
      apposition of two monolayers that line an oil-electrolyte interface. Here, a
      bilayer membrane system is developed with picoliter bubbles under mechanically
      and chemically manipulable conditions. A water bubble lined with a phospholipid
      monolayer is blown from a glass pipette into an oil phase. Two blowing pipettes
      are manipulated, and bubbles (each with a diameter of ~ 50 MUm) are held side by
      side to form a bilayer, which is termed a contact bubble bilayer. With the
      electrode implemented in the blowing pipette, currents through the bilayer are
      readily measured. The intra-bubble pressure is varied with the pressure
      controller, leading to various sizes of the bubble and the membrane area. A rapid
      solution exchange system is developed by introducing additional pressure-driven
      injection pipettes, and the blowing pipette works as a drain. The solution is
      exchanged within 20 ms. Also, an asymmetric membrane with different lipid
      composition of each leaflet is readily formed. Example applications of this
      versatile method are presented to characterize the function of ion channels.

PMID- 25772820
TI  - Electromagnetic interference from electronic devices used in the management of
      type 1 diabetes can impair the performance of an avalanche transceiver in search
      mode.
AB  - OBJECTIVE: Portable electronic devices play an important role in the management
      of type 1 diabetes mellitus. Electromagnetic interference from electronic devices
      has been shown to impair the function of an avalanche transceiver in search mode
      (but not in transmitting mode). This study investigates the influence of
      electromagnetic interference from diabetes devices on a searching avalanche
      beacon. METHODS: The greatest distance at which an avalanche transceiver (in
      search mode) could accurately indicate the location of a transmitting transceiver
      was assessed when portable electronic devices (including an insulin pump and
      commonly used real-time continuous subcutaneous glucose monitoring system
      [rtCGMS]) were held in close proximity to each transceiver. RESULTS: The
      searching transceiver could accurately locate a transmitted signal at a distance
      of 30 m when used alone. This distance was unchanged by the Dexcom G4 rtCGMS, but
      was reduced to 10 m when the Medtronic Guardian rtCGMS was held close (within 30
      cm) to the receiving beacon. Interference from the Animas Vibe insulin pump
      reduced this distance to 5 m, impairing the searching transceiver in a manner
      identical to the effect of a cell phone. CONCLUSIONS: Electromagnetic
      interference produced by some diabetes devices when held within 30 cm of a
      searching avalanche transceiver can impair the ability to locate a signal. Such
      interference could significantly compromise the outcome of a companion rescue
      scenario. Further investigation using other pumps and rtCGMS devices is required
      to evaluate all available diabetes electronics. Meantime, all electronic diabetes
      devices including rtCGMS and insulin pumps should not be used within 30 cm of an
      avalanche transceiver.

PMID- 25772821
TI  - High altitude cerebral edema-serial MRI findings.

PMID- 25772822
TI  - How not to train your dragon: a case of a Komodo dragon bite.
AB  - Komodo dragons (Varanus komodoensis) are the world's largest lizards, known for
      killing prey that exceed their body mass. Reports of bites to humans in the
      popular press suggest high degrees of morbidity and mortality. Reports in the
      medical literature are lacking. We describe the case of a zookeeper who was
      bitten by a Komodo dragon, with a resultant mallet finger. We further discuss the
      various potential mechanisms of Komodo dragon lethality, including sepsis and
      venom deposition theories that are useful in guiding management. 

PMID- 25772823
TI  - Improvised Method for Increasing the Temperature of an i-STAT Analyzer and
      Cartridge in Cold Environments.

PMID- 25772824
TI  - The Epidemiology of Caving Fatalities in the United States.

PMID- 25772825
TI  - Work patterns dictate energy demands and thermal strain during wildland
      firefighting.
AB  - OBJECTIVE: The purpose of this investigation was to characterize the effects of
      self-selected work activity on energy expenditure, water turnover, and thermal
      strain during wildland fire suppression. A secondary aim was to contrast current
      data with data collected 15 years ago using similar methods to determine whether
      job demands have changed. METHODS: Participants (n=15, 26+/-3 years, 179+/-6 cm,
      78.3+/-8.6 kg) were monitored for 3 days for total energy expenditure, water
      turnover, core and chest skin temperature, physical activity, and heart rate.
      Participants arrived to the mobile laboratory each morning, submitted a nude
      weight, ingested a temperature transmitter, provided a urine sample, and were
      equipped with a physiological and activity monitor. Participants completed live
      wildland fire suppression during their work shifts. RESULTS: Mean core
      temperature was 37.6 degrees +/-0.2 degrees C, mean chest skin temperature was
      34.1 degrees +/-1.0 degrees C, mean heart rate was 112+/-13 beats/min, and the
      mean physiological strain index score was 3.3+/-1.0. Wildland firefighters spent
      49+/-8%, 39+/-6%, and 12+/-2% in the sedentary, light, and moderate-vigorous
      intensity categories, respectively. The mean total energy expenditure was 19.1+/
      3.9 MJ/d, similar to 1997 (17.5+/-6.9 MJ/d). The mean water turnover in 2012 was
      9.5+/-1.7 L/d, which was higher (P<.05) compared with 1997-98 (7.0+/-1.7 L/d).
      CONCLUSIONS: Wildland firefighters do not induce consistently high cardiovascular
      and thermal strain while completing arduous work in a hot environment despite
      fairly high chest skin temperatures. The total energy expenditure in the current
      study suggests job demands are similar to those of 15 years ago, while the
      increased water turnover may reflect a change in drinking habits.

PMID- 25772826
TI  - Electronic tablet augmented simulation: a pilot study.

PMID- 25772827
TI  - Prediction of physiological responses and performance at altitude using the 6
      minute walk test in normoxia and hypoxia.
AB  - OBJECTIVE: The 6-minute walk test (6MWT) is a reliable and valid tool for
      determining an individual's functional capacity, and has been used to predict
      summit success. The primary aim of the study was to evaluate whether a 6MWT in
      normobaric hypoxia could predict physiological responses and exercise performance
      at altitude. The secondary aim was to determine construct validity of the 6MWT
      for monitoring acclimatization to 3400 m (Cuzco, Peru). METHODS: Twenty-nine
      participants performed six 6MWTs in four conditions: normoxic outdoor (NO),
      normoxic treadmill (NT), and hypoxic treadmill (HT) were each performed once; and
      hypoxic outdoor (HO) was performed three times, at 42 hours (HO1), 138 hours
      (HO2), and 210 hours (HO3) after arrival at Cuzco. RESULTS: One-way analysis of
      variance revealed no difference (P>.05) between NO and HO1 for 6MWT distance. HT
      and HO protocols were comparable for the measurement of delta heart rate (HR) and
      post-test peripheral oxygen saturation (%Spo2; P>.05). Acclimatization was
      evidenced by reductions (P<.05) in resting HR and respiratory rate (RR) between
      HO1, HO2, and HO3, and preservation of Spo2 between HO1 and HO2. Postexercise HR
      and RR were not different (P>.05) with acclimatization. The duration to ascend to
      4215 m on a trek was moderately correlated (P<.05) to HR during the trek and the
      6MWT distance during HT; no other physiological markers predicted performance.
      CONCLUSIONS: The 6MWT is a simple, time-efficient tool for predicting
      physiological responses to simulated and actual altitude, which are comparable.
      The 6MWT is effective at monitoring elements of acclimatization to moderate
      altitude.

PMID- 25772828
TI  - Impaired regulation of portal venous flow in response to a meal challenge as
      quantified by 4D flow MRI.
AB  - PURPOSE: Portal and mesenteric hemodynamics is greatly altered in portal
      hypertension patients. This study utilizes 4D flow magnetic resonance imaging
      (MRI) to visualize and quantify changes in abdominal hemodynamics in patients
      with portal hypertension undergoing meal challenge. MATERIALS AND METHODS: Twelve
      portal hypertension patients and six healthy subjects participated in the study.
      Baseline MRI was acquired after 5 hours of fasting. Postmeal MRI was obtained 20
      minutes after subjects ingested EnSure Plus (574 mL). Imaging was performed at 3T
      using 4D flow MRI with an undersampled radial acquisition. Flow measurements were
      performed blinded to subject status (fasting/meal). Flow values for each vessel
      were compared before and after the meal challenge using paired Student's t-tests
      (P < 0.05). RESULTS: After meal challenge, significant increases in blood flow
      were observed in supraceliac aorta, portal vein, superior mesenteric vein, and
      artery in both groups (P < 0.05). In patients, hepatic artery (P = 0.001) and
      splenic vein (P = 0.045) flow decreased while azygos vein flow (P = 0.002)
      increased. CONCLUSION: Portal venous flow regulation to adjust the increasing
      mesenteric venous flow after a meal challenge may be impaired in patients with
      cirrhosis. The ability to comprehensively quantify the hemodynamic response of
      the abdominal vasculature to a meal challenge using 4D flow MRI reveals the
      potential of this technique to noninvasively characterize portal hypertension
      hemodynamics.

PMID- 25772829
TI  - Impact-induced muscle damage and urinary pterins in professional rugby: 7,8
      dihydroneopterin oxidation by myoglobin.
AB  - Muscle damage caused through impacts in rugby union is known to increase
      oxidative stress and inflammation. Pterins have been used clinically as markers
      of oxidative stress, inflammation, and neurotransmitter synthesis. This study
      investigates the release of myoglobin from muscle tissue due to force-related
      impacts and how it is related to the subsequent oxidation of 7,8-dihydroneopterin
      to specific pterins. Effects of iron and myoglobin on 7,8-dihydroneopterin
      oxidation were examined in vitro via strong cation-exchange high-performance
      liquid chromatography (SCX-HPLC) analysis of neopterin, xanthopterin, and 7,8
      dihydroxanthopterin. Urine samples were collected from 25 professional rugby
      players pre and post four games and analyzed for myoglobin by enzyme-linked
      immunosorbent assay, and 7,8-dihydroneopterin oxidation products by HPLC. Iron
      and myoglobin oxidized 7,8-dihydroneopterin to neopterin, xanthopterin, and 7,8
      dihydroxanthopterin at concentrations at or above 10 MUM and 50 MUg/mL,
      respectively. All four games showed significant increases in myoglobin,
      neopterin, total neopterin, biopterin, and total biopterin, which correlated
      between each variable (P < 0.05). Myoglobin and iron facilitate 7,8
      dihydroneopterin oxidation to neopterin and xanthopterin. In vivo delocalization
      of myoglobin due to muscle damage may contribute to oxidative stress and
      inflammation after rugby. Increased concentrations of biopterin and total
      biopterin may indicate production of nitric oxide and monoamine neurotransmitters
      in response to the physical stress.

PMID- 25772830
TI  - The differences between two selected intensive care units located in central and
      northern Europe - preliminary observation.
AB  - BACKGROUND: The aim of this study was to evaluate possible differences in the
      functioning of two selected intensive care units in Poland and Finland. The
      activity of the units was analysed over a period of one year. METHODS: The
      following parameters were compared: demography of treated populations, site of
      admission, category of illness, severity of illness (APACHE-II scale), mean
      length of stay, demanded workload (TISS-28 scale), mortality (both ICU and
      hospital) and standardized mortality ratio (SMR). RESULTS: The results of this
      study indicated that most of the patients in the Polish ICU, regardless of age,
      diagnosis and APACHE II score, presented significantly longer lengths of stay
      (14.65 +/- 13.6 vs 4.1 +/- 4.7 days, P = 0.0001), higher mean TISS-28 score (38.9
      +/- 9.1 vs 31.2 +/- 6.1, P = 0.0001) and higher ICU and hospital mortality (41.5%
      vs 10.2% and 44.7% vs 21.8%, respectively, P = 0.0001). The values of SMR were
      0.9 and 0.85 for the Finnish and Polish ICUs, respectively. CONCLUSION: The
      collected data indicate huge differences in the utilisation of critical care
      resources. Treatment in Polish ICU is concentrated on much more severely ill
      patients which might be sometimes accompanied by futility of care. In order to
      verify and correctly interpret the presented phenomena, further studies are
      needed.

PMID- 25772831
TI  - The thorny way of 3D strain from research to clinical use: are we getting closer?

PMID- 25772832
TI  - Aortic valve area calculation in aortic stenosis by CT and Doppler
      echocardiography.
AB  - OBJECTIVES: The aim of this study was to verify the hypothesis that multidetector
      computed tomography (MDCT) is superior to echocardiography for measuring the left
      ventricular outflow tract (LVOT) and calculating the aortic valve area (AVA) with
      regard to hemodynamic correlations and survival outcome prediction after a
      diagnosis of aortic stenosis (AS). BACKGROUND: MDCT demonstrated that the LVOT is
      noncircular, casting doubt on the AVA measurement by 2-dimensional (2D)
      echocardiography. METHODS: A total of 269 patients (76 +/- 11 years of age, 61%
      men) with isolated calcific AS (mean gradient 44 +/- 18 mm Hg; ejection fraction
      58 +/- 15%) underwent Doppler echocardiography and MDCT within the same episode
      of care. AVA was calculated by echocardiography (AVAEcho) and by MDCT (AVACT)
      using each technique measurement of LVOT area. In the subset of patients
      undergoing dynamic 4-dimensional MDCT (n = 135), AVA was calculated with the LVOT
      measured at 70% and 20% of the R-R interval and measured by planimetry
      (AVAPlani). RESULTS: Phasic measurements of the LVOT by MDCT yielded slight
      differences in eccentricity and size (all p < 0.001) but with excellent AVA
      correlation (r = 0.92, p < 0.0001) and minimal bias (0.05 cm(2)), whereas the
      AVAPlani showed poor correlations with all other methods (all r values <0.58).
      AVACT was larger than AVAEcho (difference 0.12 +/- 0.16 cm(2); p < 0.0001) but
      did not improve outcome prediction. Correlation gradient-AVA was slightly better
      with AVAEcho than AVACT (r = -0.65 with AVAEcho vs. -0.61 with AVACT; p = 0.01),
      and discordant gradient-AVA was not reduced. For long-term survival, after
      multivariable adjustment, AVAEcho or AVACT were independently predictive (hazard
      ratio [HR]: 1.26, 95% confidence interval [CI]: 1.13 to 1.42; p < 0.0001 or HR:
      1.18, 95% CI: 1.09 to 1.29 per 0.10 cm(2) decrease; p < 0.0001) with a similar
      prognostic value (p >= 0.80). Thresholds for excess mortality differed between
      methods: AVAEcho <=1.0 cm(2) (HR: 4.67, 95% CI: 2.22 to 10.50; p < 0.0001) versus
      AVACT <=1.2 cm(2) (HR: 3.16, 95% CI: 1.64 to 6.43; p = 0.005), with simple
      translation of spline-curve analysis. CONCLUSIONS: Head-to-head comparison of
      MDCT and Doppler echocardiography refutes the hypothesis of MDCT superiority for
      AVA calculation. AVACT is larger than AVAEcho but does not improve the
      correlation with transvalvular gradient, the concordance gradient-AVA, or
      mortality prediction compared with AVAEcho. Larger cut-point values should be
      used for severe AS if AVACT (<1.2 cm(2)) is measured versus AVAEcho (<1.0 cm(2)).

PMID- 25772833
TI  - Stenotic aortic valve area: should it be calculated from CT instead of
      echocardiographic data?

PMID- 25772834
TI  - Recommendations for comprehensive intraprocedural echocardiographic imaging
      during TAVR.
AB  - Recent multicenter trials have shown that transcatheter aortic valve replacement
      is an alternative to surgery in a high risk population of patients with severe,
      symptomatic aortic stenosis. Echocardiography and multislice computed tomographic
      imaging are accepted tools in the pre-procedural imaging of the aortic valve
      complex and vascular access. Transesophageal echocardiography can be valuable for
      intraprocedural confirmation of the landing zone morphology and measurements,
      positioning of the valve and post-procedural evaluation of complications. The
      current paper provides recommendations for pre-procedural and intraprocedural
      imaging used in assessing patients for transcatheter aortic valve replacement
      with either balloon-expandable or self-expanding transcatheter heart valves. 

PMID- 25772836
TI  - Echocardiographic imaging of procedural complications during self-expandable
      transcatheter aortic valve replacement.
AB  - Transcatheter aortic valve replacement (TAVR) with the use of the self-expandable
      Revalving system is an accepted alternative to surgical replacement for severe,
      symptomatic aortic stenosis in high-risk or inoperable patients. Intraprocedural
      imaging relies on fluoroscopic guidance, with echocardiographic imaging used as a
      supportive imaging modality. Intraprocedural transthoracic echocardiography (TTE)
      and transesophageal echocardiography (TEE) offer real-time imaging guidance
      throughout the procedure and may contribute to improving procedural results.
      Registries suggest that TAVR may be performed in lower-surgical-risk patients
      with equal outcomes to high-risk patients with ongoing randomized trials
      comparing these results with surgical outcomes. Understanding the utility of
      echocardiographic imaging in diagnosing or preventing complications may be
      particularly important as we move toward these lower-risk patient populations.
      This imaging compendium is intended to be a comprehensive compilation of
      intraprocedural complications imaged by intraprocedural echocardiography. 

PMID- 25772837
TI  - A picture (and a video) is worth a....

PMID- 25772835
TI  - Echocardiographic imaging of procedural complications during balloon-expandable
      transcatheter aortic valve replacement.
AB  - Transcatheter aortic valve replacement (TAVR) using a balloon-expandable valve is
      an accepted alternative to surgical replacement for severe, symptomatic aortic
      stenosis in high risk or inoperable patients. Intraprocedural transesophageal
      echocardiography (TEE) offers real-time imaging guidance throughout the procedure
      and allows for rapid and accurate assessment of complications and procedural
      results. The value of intraprocedural TEE for TAVR will likely increase in the
      future as this procedure is performed in lower surgical risk patients, who also
      have lower risk for general anesthesia, but a greater expectation of optimal
      results with lower morbidity and mortality. This imaging compendium from the
      PARTNER (Placement of Aortic Transcatheter Valves) trials is intended to be a
      comprehensive compilation of intraprocedural complications imaged by
      intraprocedural TEE and diagnostic tools to anticipate and/or prevent their
      occurrence. 

PMID- 25772838
TI  - Assessment of paravalvular regurgitation following TAVR: a proposal of unifying
      grading scheme.
AB  - Paravalvular regurgitation (PVR) is a frequent complication of transcatheter
      aortic valve replacement that has been shown to be associated with increased
      mortality. The objective of this article is to review the most up-to-date
      information about the assessment and management of PVR and to propose a new more
      comprehensive and unifying scheme for grading PVR severity. A multimodality,
      multiparametric, integrative approach including Doppler echocardiography,
      cineangiography, hemodynamic assessment, and/or cardiac magnetic resonance is
      essential to accurately assess the severity of PVR and the underlying etiology.
      Corrective procedures such as balloon post-dilation, valve-in-valve, or leak
      closure may be considered, depending on the severity, location, and etiology of
      PVR. 

PMID- 25772839
TI  - Optimal imaging for guiding TAVR: transesophageal or transthoracic
      echocardiography, or just fluoroscopy?

PMID- 25772840
TI  - Integrated 3D echo-x ray to optimize image guidance for structural heart
      intervention.

PMID- 25772841
TI  - Noncontrast 3D CMR imaging for aortic valve annulus sizing in TAVR.

PMID- 25772842
TI  - Transthoracic echocardiography guidance for TAVR under monitored anesthesia care.

PMID- 25772843
TI  - Valvular disease, myocardial mechanics, and valve guidelines.

PMID- 25772844
TI  - Reply: Valvular disease, myocardial mechanics, and valve guidelines.

PMID- 25772845
TI  - The symphony, the ensemble, and the interventional imager....

PMID- 25772846
TI  - Novel Active Learning Experiences for Students to Identify Barriers to
      Independent Living for People with Disabilities.
AB  - PURPOSE: This article describes interactive learning about independent living for
      people with disabilities and features the partnership of the College of Nursing
      and a Center for Independent Living (CIL). DESIGN: Using qualitative descriptive
      approach, students' written reflections were analyzed. METHODS: Through "Xtreme
      Challenge," 82 undergraduate nursing students participated in aspects of
      independent living as well as identifying barriers. FINDINGS: Students were
      engaged and learned to consider the person before the disability. Moreover,
      students valued the activity leaders' openness, which facilitated understanding
      the point of view of a person with disability. CONCLUSIONS: The value of
      partnership was evident as it allowed students to participate in active learning,
      which led to growth in the affective domain. Students became aware of potential
      education resources through the CIL. CLINICAL RELEVANCE: This article will guide
      educators in designing experiences that teach nursing care at the individual,
      family, and community level for people living with disabilities.

PMID- 25772847
TI  - Exploiting human and mouse transcriptomic data: Identification of circadian genes
      and pathways influencing health.
AB  - The power of the application of bioinformatics across multiple publicly available
      transcriptomic data sets was explored. Using 19 human and mouse circadian
      transcriptomic data sets, we found that NR1D1 and NR1D2 which encode heme
      responsive nuclear receptors are the most rhythmic transcripts across sleep
      conditions and tissues suggesting that they are at the core of circadian rhythm
      generation. Analyzes of human transcriptomic data show that a core set of
      transcripts related to processes including immune function, glucocorticoid
      signalling, and lipid metabolism is rhythmically expressed independently of the
      sleep-wake cycle. We also identify key transcripts associated with transcription
      and translation that are disrupted by sleep manipulations, and through network
      analysis identify putative mechanisms underlying the adverse health outcomes
      associated with sleep disruption, such as diabetes and cancer. Comparative
      bioinformatics applied to existing and future data sets will be a powerful tool
      for the identification of core circadian- and sleep-dependent molecules. 

PMID- 25772848
TI  - Cilostazol improves hepatic blood perfusion, microcirculation, and liver
      regeneration after major hepatectomy in rats.
AB  - Major hepatectomy or small-for-size liver transplantation may result in
      postoperative liver failure. So far, no treatment is available to improve liver
      regeneration. Herein, we studied whether cilostazol, a selective
      phosphodiesterase III inhibitor, is capable of improving liver regeneration after
      major hepatectomy. Sprague-Dawley rats (n = 74) were treated with cilostazol (5
      mg/kg daily) or a glucose solution and underwent either 70% liver resection or a
      sham operation. Before and after surgery, hepatic arterial and portal venous
      blood flow and hepatic microvascular perfusion were analyzed. Liver morphology,
      function, and regeneration were studied with histology, immunohistochemistry,
      western blotting, and bile excretion analysis. Cilostazol significantly increased
      hepatic blood flow and microcirculation before and after hepatectomy in
      comparison with sham-operated controls. This was associated with an elevation of
      hepatic vascular endothelial growth factor expression, an increase of
      hepatocellular proliferation, and an acceleration of liver regeneration.
      Furthermore, cilostazol protected the tissue of the remnant liver as indicated by
      an attenuation of hepatocellular disintegration. In conclusion, cilostazol
      increases hepatic blood perfusion, microcirculation, and liver regeneration after
      a major hepatectomy. Thus, cilostazol may represent a novel strategy to reduce
      the rate of liver failure after both extended hepatectomy and small-for-size
      liver transplantation.

PMID- 25772849
TI  - Supplementation with sunflower seed increases circulating cholesterol
      concentrations and potentially impacts on the pregnancy rates in Bos indicus beef
      cattle.
AB  - We aimed to evaluate the effect of supplementation with sunflower seed on blood
      concentrations of progesterone and cholesterol and on the pregnancy rate in beef
      cattle subjected to timed artificial insemination (TAI) and timed embryo transfer
      (TET). In experiment 1, cows were received 22-day supplements containing
      (sunflower, n = 66) sunflower seed or not (control, n = 67) immediately after a
      progesterone/estradiol-based TAI protocol (Day 0). The cholesterol concentration
      on Day 21 and the pregnancy rate were greater (P < 0.03) in the sunflower group
      (148.2 +/- 6.1 mg/dL and 66.7%) than those in the control group (116.0 +/- 6.4
      mg/dL and 47.8%). In experiment 2, heifers received an in vitro-produced embryo 7
      days after the expected time of the synchronized ovulation. Heifers were
      separated into two supplementation groups (sunflower, n = 106 and control, n =
      111) for 22 days. The plasma progesterone concentration on Day 7 was not
      different between the groups. However, on Day 19, the plasma progesterone
      concentration was greater (P < 0.0001) in the sunflower group (5.8 +/- 0.4 ng/mL)
      than that in the control group (3.5 +/- 0.4 ng/mL). A greater (P < 0.05)
      cholesterol concentration was observed in the sunflower group than that in the
      control group on Days 7 (306.0 +/- 11.6 vs. 277.1 +/- 11.9 mg/dL, respectively)
      and 19 (260.5 +/- 8.0 vs. 232.0 +/- 8.0 mg/dL, respectively). The pregnancy rate
      was greater (P = 0.01) in the sunflower-treated heifers (55.7%) than that in
      control-treated heifers (36.9%). Results indicate that sunflower seed
      supplementation increases the circulating cholesterol concentrations and
      potentially impacts the pregnancy rate in suckled beef cattle subjected to TAI or
      TET.

PMID- 25772850
TI  - Effect of semen extender supplementation with cysteine on postthaw sperm quality,
      DNA damage, and fertilizing ability in the common carp (Cyprinus carpio).
AB  - Amino acids have an important biological role for prevention of cell damage
      during cryopreservation. The objective of this study is to determine the effects
      of cysteine on postthaw sperm motility, duration of sperm motility, DNA damage,
      and fertility in the common carp (Cyprinus carpio). Sperm collected from 10
      individuals was cryopreserved in extenders containing different cysteine
      concentrations (2.5, 5, 10, and 20 mM). Semen samples diluted at the ratio of 1:9
      by the extenders were subjected to cryopreservation. After dilution, the semen
      was aspirated into 0.25-mL straws; the straws were placed on the tray, frozen in
      nitrogen vapor, and plunged into liquid nitrogen. DNA damage was evaluated by
      comet assay after cryopreservation. Our results indicated that an increase in the
      concentration of cysteine caused a significant increase in the motility rate and
      duration of sperm in the common carp (C carpio; P < 0.05). Comparing all
      concentrations of cysteine, the best concentration of cysteine was 20 mM. Higher
      postthaw motility (76.00 +/- 1.00%) and fertilization (97.00 +/- 1.73%) rates
      were obtained with the extender at the concentration of 20 mM. Supplementation of
      the extender with cysteine was increased the fertilization and hatching rate and
      decreased DNA damage. Consequently, cysteine affected the motility,
      fertilization, and DNA damage positively, and extenders could be supplemented
      with cysteine.

PMID- 25772851
TI  - Identification and comparison of gonadal transcripts of testis and ovary of adult
      common carp Cyprinus carpio using suppression subtractive hybridization.
AB  - The limited number of gonad-specific and gonad-related genes that have been
      identified in fish represents a major obstacle in the study of fish gonad
      development and sex differentiation. In common carp Cyprinus carpio from China's
      Yellow River, the ovary and testis differ in volume and weight in adult fish of
      the same age. Comparing sperm, egg, and somatic cell transcripts in this carp may
      provide insight into the mechanisms of its gonad development and sex
      differentiation. In the present work, gene expression patterns in the carp ovary
      and testis were compared using suppression subtractive hybridization. Two
      bidirectional subtracted complementary DNA (cDNA) libraries were analyzed in
      parallel using testis or ovary as testers. Eighteen nonredundant clones were
      identified in the male library, including 15 known cDNAs. The expression patterns
      of selected genes in testis and ovary were analyzed using reverse transcriptase
      polymerase chain reaction. Tektin-1, GAPDS, FGFIBP, IGFBP-5, and an unknown gene
      from the Ccmg4 clone were observed to be expressed only in testis. GSDF, BMI1b,
      Wt1a, and an unknown gene from the Ccme2 clone were expressed at higher levels in
      testis than in ovary at sexual maturity. Thirty functional expressed sequence
      tags (ESTs) were identified in 43 sequenced clones in the female library,
      including 28 known cDNAs, one uncharacterized cDNA (EST clone), and one novel
      sequence. Eight identified ESTs showed significant differences in expression
      between the testis and the ovary. ZP3C and Psmb2 were expressed exclusively in
      ovary, whereas the expression levels of IFIPGL-1, Setd6, ATP-6, CDC45, AIF-1, and
      an unknown gene from the Ccfh2 clone were more strongly expressed in ovary than
      in testis. In addition, the expression of ZP3C, Wt1a, and Setd6 was analyzed in
      male and female gonads, heart, liver, kidney, and brain. ZP3C was expressed only
      in ovary. Setd6 expression was significantly stronger in female tissues than that
      in the male, except in the liver, and Wt1a expression showed sexual dimorphism in
      the kidney and liver. Results suggest that these genes could play key roles
      during carp growth, both in the gonad and other tissues. The results provide a
      resource for further investigation of molecular mechanisms responsible for gonad
      development and sex differentiation in Yellow River common carp.

PMID- 25772853
TI  - The ethical implications and religious significance of organ transplantation
      payment systems.
AB  - One of the more polarizing policies proposed to alleviate the organ shortage is
      financial payment of donors in return for organs. A priori and empirical
      investigation concludes that such systems are ethically inadequate. A new
      methodological approach towards policy formation and implementation is proposed
      which places ethical concerns at its core. From a hypothetical secular origin,
      the optimal ethical policy structure concerning organ donation is derived.
      However, when applied universally, it does not yield ideal results for every
      culture and society due to region-specific variation. Since religion holds
      significant influence in the organ donation debate, three religions-Catholicism,
      Islam, and Shinto-were examined in order to illustrate this variation. Although
      secular ethical concerns should rest at the core of policy construction, certain
      region-specific contexts require cultural and religious competence and
      necessitate the adjustment of the optimal template policy accordingly to yield
      the best moral and practical results. 

PMID- 25772854
TI  - The Donor Kidney Biopsy and Its Implications in Predicting Graft Outcomes: A
      Systematic Review.
AB  - Despite a growing organ shortage in the United States, many deceased donor
      kidneys removed for transplantation are discarded. Kidney biopsy findings often
      play a role in these discards, although it is not clear whether biopsies reliably
      inform acceptance decisions. Therefore, we carried out a systematic review of the
      medical literature on the utility of both procurement and implantation biopsies
      for predicting posttransplant outcomes. Between January 1, 1994 and July 1, 2014,
      47 studies were published in the English language literature that examined the
      association between pretransplant donor biopsy findings from 50 or more donors
      (with more than half being from deceased donors) and either posttransplant graft
      failure, delayed graft function, or graft function. In general, study quality was
      poor. All were retrospective or did not indicate if they were prospective.
      Results were heterogeneous, with authors as often as not concluding that biopsy
      results did not predict posttransplant outcomes. The percent glomerular sclerosis
      was most often examined, and failed to predict graft failure in 7 of 14 studies.
      Of 15 semiquantitative scoring systems proposed, none consistently predicted
      posttransplant outcomes across studies. Routine use of biopsies to help determine
      whether or not to transplant a kidney should be reexamined. 

PMID- 25772855
TI  - Clinical features and endoscopic findings in patients with actively bleeding
      colonic angiodysplasia.
AB  - Colonic angiodysplasia (AGD) is an important cause of lower gastrointestinal
      bleeding. However, most episodes of bleeding from colonic AGD stop spontaneously.
      To date, few data are available regarding the endoscopic findings of bleeding
      colonic AGD. In order to clarify the clinical features and endoscopic findings of
      actively bleeding colonic AGD, we conducted a retrospective study of patients
      treated with colonoscopy at our hospital. From November 2006 to March 2013
      inclusive, 32,586 colonoscopies were performed at this hospital, among which 13
      patients with bleeding colonic AGD were enrolled in the current study. The mean
      age was 84 years (range: 69-90 years). All patients had chronic heart disease and
      were currently using anticoagulant and/or antiplatelet drugs. Sites of bleeding
      AGD were localized in the left colon in two patients (15 %) and in the right
      colon in the remaining patients (85 %). A total of 77 % of the lesions (10/13)
      were 1-2 mm in size and two lesions were 4 mm in size; only one lesion was larger
      than 5 mm. Endoscopic treatment resulted in a therapeutic success rate of 100 %,
      and no recurrence of bleeding was observed in 85 % of the patients (11/13) after
      treatment. During the study period, two patients presented with bleeding from
      residual AGD and underwent endoscopic treatment. In the present study, most sites
      of bleeding colonic AGD were very small, termed "micro-angiodysplasia", and
      targeted endoscopic treatment for actively bleeding AGD was found to be effective
      and safe. It is essential that physicians consider the potential for actively
      bleeding colonic AGD, especially "micro-angiodysplasia", when performing
      colonoscopy in elderly patients with a history of cardiovascular disease and/or
      treatment with anticoagulant or antiplatelet therapy. 

PMID- 25772857
TI  - ALK-Positive Inflammatory Myofibroblastic Tumor of the Nipple During Pregnancy-An
      Unusual Presentation of a Rare Disease.
AB  - Inflammatory myofibroblastic tumors (IMT) is a benign to low-grade malignant
      neoplasm most commonly occurring in the viscera and soft tissues of children and
      young adults. Involvement of the breast is very rare. This report presents the
      first case of IMT of the nipple and highlights the histologic features and
      differential diagnosis at this unusual anatomical site. The patient was a 31
      years-old pregnant woman with a palpable mass at the upper half of the left
      nipple. The lesion appeared after breastfeeding of her first child and increased
      in size during her second pregnancy. A conservative, incomplete surgical excision
      was performed in the 24th week of the second pregnancy. The residual tumor
      subsequently underwent spontaneous regression. There was no evidence of disease 5
      years after surgery. FISH and immunohistochemical analyses revealed rearrangement
      and overexpression of the ALK gene, a typical feature of both pulmonary and
      extrapulmonary IMT.

PMID- 25772858
TI  - Patulin triggers NRF2-mediated survival mechanisms in kidney cells.
AB  - Patulin (PAT), a mycotoxin contaminant of apples and apple products, has been
      implicated in nephrotoxicity. PAT depletes glutathione (GSH) and elevates
      reactive oxygen species (ROS). The antioxidant (AO) response is activated by
      Nuclear erythroid 2-related factor (NRF2) and enhanced by Silent information
      regulator 3 (SIRT3). The effects of PAT on these molecules have yet to be
      examined. We investigated the effects of PAT on AO response survival pathways in
      human embryonic kidney cells (HEK293). PAT cytotoxicity on HEK293 cells was
      evaluated (MTT assay; 24 h; [0-100 MUM]) to determine an IC50. GSH levels were
      measured using luminometry. Intracellular ROS was evaluated by flow cytometry.
      Protein expression of Keap1, NRF2, SIRT3 and PGC-1alpha was quantified by western
      blotting and gene expression of SOD2, CAT and GPx was evaluated by qPCR. PAT
      caused a dose dependent decrease in HEK293 cell viability and a significant
      increase in levels of intracellular ROS (p = 0.0006). A significant increase in
      protein expression (p = 0.029) was observed. PAT increased gene expression of
      SOD2 and CAT (p = 0.0043), however, gene expression of GPx was significantly
      reduced (p = 0.0043). These results show the up-regulation of NRF2 mediated AO
      mechanisms in response to PAT toxicity. 

PMID- 25772856
TI  - Indian Society of Gastroenterology consensus statements on Crohn's disease in
      India.
AB  - In 2012, the Indian Society of Gastroenterology's Task Force on Inflammatory
      Bowel Diseases undertook an exercise to produce consensus statements on Crohn's
      disease (CD). This consensus, produced through a modified Delphi process,
      reflects our current recommendations for the diagnosis and management of CD in
      India. The consensus statements are intended to serve as a reference point for
      teaching, clinical practice, and research in India. 

PMID- 25772859
TI  - The relative toxicity of Delphinium stachydeum in mice and cattle.
AB  - Larkspurs (Delphinium spp.) are poisonous plants on rangelands throughout the
      Western United States and Canada. Larkspur-induced poisoning in cattle is due to
      norditerpene alkaloids that are represented by two main structural groups of
      norditerpene alkaloids, the N-(methylsuccinimido) anthranoyllycoctonine type
      (MSAL-type) and the non-MSAL type. Information on the alkaloid composition and
      resulting toxicity in mice and cattle is lacking for a number of Delphinium
      species, including Delphinium stachydeum. The objective of this study was to
      determine the alkaloid composition of D. stachydeum and to characterize its
      relative toxicity in mice and cattle compared to two reference species Delphinium
      barbeyi and Delphinium occidentale. D. stachydeum contains the non-MSAL-type
      alkaloids but not the MSAL-type alkaloids. D. stachydeum was less toxic than D.
      barbeyi and D. occidentale in the mouse model. D. stachydeum was less toxic than
      the MSAL-containing D. barbeyi but much more toxic than the non-MSAL-containing
      D. occidentale in cattle as measured by heart rate and time of exercise. These
      results indicate that predictions of Delphinium toxicity can't be accurately made
      based solely on results from the mouse model or the absence of the MSAL-type
      alkaloids in the plant. 

PMID- 25772860
TI  - Identification and characterization of an antimicrobial peptide of Hypsiboas
      semilineatus (Spix, 1824) (Amphibia, Hylidae).
AB  - The multidrug-resistant bacteria have become a serious problem to public health.
      In this scenery the antimicrobial peptides (AMPs) derived from animals and plants
      emerge as a novel therapeutic modality, substituting or in addition to the
      conventional antimicrobial. The anurans are one of the richest natural sources of
      AMPs. In this work several cycles of cDNA cloning of the skin of the Brazilian
      treefrog Hypsiboas semilineatus led to isolation of a precursor sequence that
      encodes a new AMP. The sequence comprises a 27 residue signal peptide, followed
      by an acidic intervening sequence that ends in the mature peptide at the carboxy
      terminal. The AMP, named Hs-1, has 20 amino acids residues, mostly arranged in an
      alpha helix and with a molecular weight of 2144.6 Da. The chemically synthesized
      Hs-1 showed an antimicrobial activity against all Gram-positive bacteria tested,
      with a range of 11-46 MUM, but it did not show any effect against Gram-negative
      bacteria, which suggest that Hs-1 may have a selective action for Gram-positive
      bacteria. The effects of Hs-1 on bacterial cells were also demonstrated by
      transmission electron microscopy. Hs-1 is the first AMP to be described from H.
      semilineatus. 

PMID- 25772861
TI  - Fear of Self and Unacceptable Thoughts in Obsessive-Compulsive Disorder.
AB  - Cognitive-behavioural models have linked unacceptable or repugnant thoughts in
      obsessive-compulsive disorder (OCD) with vulnerable self-themes and fear-of-self
      concerns. To investigate this notion, Aardema and coworkers recently developed
      and validated the Fear of Self-Questionnaire (FSQ) in non-clinical samples,
      finding it had strong internal inconsistency, and good divergent and convergent
      validity, including strong relationships to obsessional symptoms and with other
      processes implicated in cognitive models of OCD (e.g., obsessive beliefs and
      inferential confusion). The current article describes two studies that aim to
      replicate and extend these findings in clinical OCD and non-clinical samples.
      Study 1 investigated the psychometric properties of an Italian translation of the
      FSQ in a non-clinical sample (n = 405). Results of confirmatory factor analysis
      supported the unidimensionality of the scale; the FSQ also showed very good
      internal consistency and temporal stability. Study 2 investigated the role of
      fear of self in OCD symptoms, and unacceptable thoughts and repugnant obsessions
      in particular, using a clinical OCD sample (n = 76). As expected, fear of self
      was a unique, major predictor of unacceptable thoughts independent of negative
      mood states and obsessive beliefs. Moreover, even when considered with obsessive
      beliefs, anxiety and depression, the feared self was the only unique predictor of
      obsessionality, providing support for the notion that self-themes could explain
      why some intrusions convert into obsessions, whereas others do not. Implications
      for current cognitive-behavioural models are discussed. Copyright (c) 2015 John
      Wiley & Sons, Ltd. KEY PRACTITIONER MESSAGE: Unacceptable thoughts in OCD have
      been linked with vulnerable self-themes and a fear of self. Aardema and coworkers
      recently developed and validated the Fear of Self-Questionnaire (FSQ). Study 1
      investigated the Psychometric properties of an Italian translation of the FSQ in
      a non-clinical sample. Study 2 investigated the role of fear of self in
      unacceptable thoughts, using a clinical OCD sample. Fear of self was a unique,
      major predictor of unacceptable thoughts in OCD over and beyond obsessive
      beliefs.

PMID- 25772862
TI  - Carcinogenic potential of PAHs in oil-contaminated soils from the main oil fields
      across China.
AB  - The concentrations, composition profiles, and sources of polycyclic aromatic
      hydrocarbons (PAHs) were analyzed in 55 surface soil samples collected from four
      oil fields across China (Daqing, DQ; Shengli, SL; Xinjiang, XJ; and Huabei, HB).
      The total 16 priority PAHs concentrations of DQ, SL, XJ, and HB ranged from 857
      to 27,816; 480 to 20,625; 497 to 43,210; and 12,112 to 45,325 ng/g, respectively,
      with means of 9160; 6394; 13,569; and 22,954 ng/g and the seven possible
      carcinogenic PAHs accounted for 8-25.7 % of the total PAHs. Almost all the
      samples were heavily contaminated, and phenanthrene, chrysene, and pyrene were
      the most dominant components. The PAH isomeric ratios indicated that PAHs in oil
      fields mainly originated from petroleum. The toxic assessment illustrated that
      people living and working in oil fields would suffer low carcinogenic risk, which
      was somehow coincided with the results of epidemiological survey on cancer
      incidence. It seems essential to pay more attention to the chronic human health
      effects of exposure to oil fields and to focus new studies on the public health
      field that involves a large number of people all over the world.

PMID- 25772864
TI  - Food waste collection and recycling for value-added products: potential
      applications and challenges in Hong Kong.
AB  - About 3600 tonnes food waste are discarded in the landfills in Hong Kong daily.
      It is expected that the three strategic landfills in Hong Kong will be exhausted
      by 2020. In consideration of the food waste management environment and community
      needs in Hong Kong, as well as with reference to the food waste management
      systems in cities such as Linkoping in Sweden and Oslo in Norway, a framework of
      food waste separation, collection, and recycling for food waste valorization is
      proposed in this paper. Food waste can be packed in an optic bag (i.e., a bag in
      green color), while the residual municipal solid waste (MSW) can be packed in a
      common plastic bag. All the wastes are then sent to the refuse transfer stations,
      in which food waste is separated from the residual MSW using an optic sensor. On
      the one hand, the sorted food waste can be converted into valuable materials
      (e.g., compost, swine feed, fish feed). On the other hand, the sorted food waste
      can be sent to the proposed Organic Waste Treatment Facilities and sewage
      treatment works for producing biogas. The biogas can be recovered to produce
      electricity and city gas (i.e., heating fuel for cooking purpose). Due to the
      challenges faced by the value-added products in Hong Kong, the biogas is
      recommended to be upgraded as a biogas fuel for vehicle use. Hopefully, the
      proposed framework will provide a simple and effective approach to food waste
      separation at source and promote sustainable use of waste to resource in Hong
      Kong. 

PMID- 25772863
TI  - Effect of biochar on the extractability of heavy metals (Cd, Cu, Pb, and Zn) and
      enzyme activity in soil.
AB  - Biochar is a carbon-rich solid material derived from the pyrolysis of
      agricultural and forest residual biomass. Previous studies have shown that
      biochar is suitable as an adsorbent for soil contaminants such as heavy metals
      and consequently reduces their bioavailability. However, the long-term effect of
      different biochars on metal extractability or soil health has not been assessed.
      Therefore, a 1-year incubation experiment was carried out to investigate the
      effect of biochar produced from bamboo and rice straw (at temperatures >=500 
      degrees C) on the heavy metal (cadmium (Cd), copper (Cu), lead (Pb), and zinc
      (Zn)) extractability and enzyme activity (urease, catalase, and acid phosphatase)
      in a contaminated sandy loam paddy soil. Three rates (0, 1, and 5%) and two mesh
      sizes (<0.25 and <1 mm) of biochar applications were investigated. After
      incubation, the physicochemical properties, extractable heavy metals, available
      phosphorus, and enzyme activity of soil samples were analyzed. The results
      demonstrated that rice straw biochar significantly (P < 0.05) increased the pH,
      electrical conductivity, and cation exchange capacity of the soil, especially at
      the 5% application rate. Both bamboo and rice straw biochar significantly (P <
      0.05) decreased the concentration of CaCl2-extractable heavy metals as biochar
      application rate increased. The heavy metal extractability was significantly (P <
      0.01) correlated with pH, water-soluble organic carbon, and available phosphorus
      in soil. The 5% application rate of fine rice straw biochar resulted in the
      greatest reductions of extractable Cu and Zn, 97.3 and 62.2%, respectively. Both
      bamboo and rice straw biochar were more effective at decreasing extractable Cu
      and Pb than removing extractable Cd and Zn from the soil. Urease activity
      increased by 143 and 107% after the addition of 5% coarse and fine rice straw
      biochars, respectively. Both bamboo and rice straw biochars significantly (P <
      0.05) increased catalase activity but had no significant impact on acid
      phosphatase activity. In conclusion, the rice straw biochar had greater potential
      as an amendment for reducing the bioavailability of heavy metals in soil than
      that of the bamboo biochar. The impact of biochar treatment on heavy metal
      extractability and enzyme activity varied with the biochar type, application
      rate, and particle size.

PMID- 25772865
TI  - Suppressive effects of long-term exposure to P-nitrophenol on gonadal
      development, hormonal profile with disruption of tissue integrity, and activation
      of caspase-3 in male Japanese quail (Coturnix japonica).
AB  - P-Nitrophenol (PNP) is considered to be one of nitrophenol derivatives of diesel
      exhaust particles. PNP is a major metabolite of some organophosphorus compounds.
      PNP is a persistent organic pollutant as well as one of endocrine-disrupting
      compounds. Consequently, bioaccumulation of PNP potentiates toxicity. The
      objectives of the current study were to assess in vivo adverse effects of long
      term low doses of PNP exposure on reproductive system during development stage.
      Twenty-eight-day-old male Japanese quails were orally administered different
      doses of PNP (0, 0.01, 0.1, 1 mg/kg body weight) daily for 2.5 months. Testicular
      histopathology, hormones, caspase-3 (CASP3), and claudin-1 (CLDN1) tight junction
      protein, as well as plasma hormones were analyzed. The results revealed that long
      term PNP exposure caused testicular histopathological changes such as vacuolation
      of spermatogenic cell and spermatocyte with significant testicular and cloacal
      gland atrophy. PNP activated CASP3 enzyme that is an apoptosis-related cysteine
      peptidase. Besides, it disrupted the expression of CLDN1. Furthermore, a
      substantial decrease in plasma concentrations of luteinizing hormone (LH) and
      testosterone was observed after 2 and 2.5 months in the PNP-treated groups.
      Meanwhile, the pituitary LH did not significantly change. Site of action of PNP
      may be peripheral on testicular development and/or centrally on the hypothalamic
      pituitary-gonadal axis through reduction of pulsatile secretion of gonadotrophin
      releasing hormone. Consequently, it may reduce the sensitivity of the anterior
      pituitary gland to secrete LH. In conclusion, PNP induced profound endocrine
      disruption in the form of hormonal imbalance, induction of CASP3, and disruption
      of CLDN1 expression in the testis. Hence, it may hinder the reproductive
      processes.

PMID- 25772866
TI  - Effects of land use change on soil gross nitrogen transformation rates in
      subtropical acid soils of Southwest China.
AB  - Land use change affects soil gross nitrogen (N) transformations, but such
      information is particularly lacking under subtropical conditions. A study was
      carried out to investigate the potential gross N transformation rates in forest
      and agricultural (converted from the forest) soils in subtropical China. The
      simultaneously occurring gross N transformations in soil were quantified by a
      (15)N tracing study under aerobic conditions. The results showed that change of
      land use types substantially altered most gross N transformation rates. The gross
      ammonification and nitrification rates were significantly higher in the
      agricultural soils than in the forest soils, while the reverse was true for the
      gross N immobilization rates. The higher total carbon (C) concentrations and C /
      N ratio in the forest soils relative to the agricultural soils were related to
      the greater gross N immobilization rates in the forest soils. The lower gross
      ammonification combined with negligible gross nitrification rates, but much
      higher gross N immobilization rates in the forest soils than in the agricultural
      soils suggest that this may be a mechanism to effectively conserve available
      mineral N in the forest soils through increasing microbial biomass N, the
      relatively labile organic N. The greater gross nitrification rates and lower
      gross N immobilization rates in the agricultural soils suggest that conversion of
      forests to agricultural soils may exert more negative effects on the environment
      by N loss through NO3 (-) leaching or denitrification (when conditions for
      denitrification exist).

PMID- 25772867
TI  - Relationships between bacterial energetic metabolism, mercury methylation
      potential, and hgcA/hgcB gene expression in Desulfovibrio dechloroacetivorans
      BerOc1.
AB  - The proteins encoded by the hgcA and hgcB genes are currently the only ones known
      to be involved in the mercury methylation by anaerobic microorganisms. However,
      no studies have been published to determine the relationships between their
      expression level and the net/gross methylmercury production. This study aimed to
      decipher the effect of growth conditions on methylmercury production and the
      relationships between hgcA and hgcB expression levels and net methylation.
      Desulfovibrio dechloroacetivorans strain BerOc1 was grown under sulfidogenic
      conditions with different carbon sources and electron donors as well as under
      fumarate respiration. A good correlation was found between the biomass production
      and the methylmercury production when the strain was grown under sulfate-reducing
      conditions. Methylmercury production was much higher under fumarate respiration
      when no sulfide was produced. During exponential growth, hgcA and hgcB gene
      expression levels were only slightly higher in the presence of inorganic mercury,
      and it was difficult to conclude whether there was a significant induction of
      hgcA and hgcB genes by inorganic mercury. Besides, no relationships between hgcA
      and hgcB expression levels and net mercury methylation could be observed when the
      strain was grown either under sulfate reduction or fumarate respiration,
      indicating that environmental factors had more influence than expression levels. 

PMID- 25772868
TI  - Synthesis and characterization of hydroxyapatite nanoparticles impregnated on
      apple pomace to enhanced adsorption of Pb(II), Cd(II), and Ni(II) ions from
      aqueous solution.
AB  - Hydroxyapatite nanoparticles were synthesized, characterized, and impregnated
      onto apple pomace surface (HANP@AP) for efficient removal of Pb(II), Cd(II), and
      Ni(II) ions from water. HANP@AP was characterized by Fourier transform infrared
      spectroscopy (FTIR), scanning electron microscopy (SEM), energy-dispersive
      spectroscopy (EDS), transmission electron microscope (TEM), X-ray diffraction
      (XRD), and surface area analysis. Batch sorption studies were carried out to
      investigate the influence of different parameters as amount of dose (g), pH, time
      (min), and initial concentration (mg L(-1)) on adsorption process. Experimental
      kinetic data followed pseudo-second-order model and equilibrium data well fitted
      to Langmuir adsorption model with maximum adsorption capacities of 303, 250, and
      100 mg g(-1) for Pb(II), Cd(II), and Ni(II) ions, respectively. Competitive
      adsorption of Pb(II), Cd(II), and Ni(II) ions in presences of each other was
      studied to evaluate the removal efficiency of HANP@AP against multi metal-loaded
      water. HANP@AP was successfully applied to real industrial wastewater with 100 %
      removal of all three metal ions even at high concentration. HANP@AP could be
      recycled for four, four, and three cycles in case of Pb(II), Cd(II) and Ni(II),
      respectively. The study showed that HANP@AP is fast, cost effective, and
      environmental friendly adsorbent for removal of Pb(II), Cd(II), and Ni(II) ions
      from real industrial wastewater.

PMID- 25772869
TI  - Bioremoval of the azo dye Congo Red by the microalga Chlorella vulgaris.
AB  - Discharge of dye-containing wastewater by the textile industry can adversely
      affect aquatic ecosystems and human health. Bioremoval is an alternative to
      industrial processes for detoxifying water contaminated with dyes. In this work,
      active and inactive biomass of the microalga Chlorella vulgaris was assayed for
      the ability to remove Congo Red (CR) dye from aqueous solutions. Through
      biosorption and biodegradation processes, Chlorella vulgaris was able to remove
      83 and 58 % of dye at concentrations of 5 and 25 mg L(-1), respectively. The
      maximum adsorption capacity at equilibrium was 200 mg g(-1). The Langmuir model
      best described the experimental equilibrium data. The acute toxicity test (48 h)
      with two species of cladocerans indicated that the toxicity of the dye in the
      effluent was significantly decreased compared to the initial concentrations in
      the influent. Daphnia magna was the species less sensitive to dye (EC50 = 17.0 mg
      L(-1)), followed by Ceriodaphnia dubia (EC50 = 3.32 mg L(-1)). These results show
      that Chlorella vulgaris significantly reduced the dye concentration and toxicity.
      Therefore, this method may be a viable option for the treatment of this type of
      effluent.

PMID- 25772870
TI  - Effect of input pathways and altitudes on spatial distribution of polycyclic
      aromatic hydrocarbons in background soils, the Tibetan Plateau.
AB  - Limited data on the spatial distribution of polycyclic aromatic hydrocarbons
      (PAHs) in Tibetan soils have been reported. This study measured the
      concentrations of PAHs in background soils across Tibet including 44 surface
      soils (0-10 cm) and 14 subsurface soils (10-20 cm) and assessed the effect of
      input pathways and altitudes on spatial distribution of PAHs. The concentrations
      of 15 US EPA priority PAHs (?15-PAHs, naphthalene excluded) in all surface soils
      ranged from 1.50 to 29.88 ng/g dry weight with a mean concentration of 6.09 ng/g.
      The levels of PAHs in soils from southeast of Tibet were higher than those from
      northwest, which might be attributed to both more local emission as a result of
      relative higher population density and contributions of long-range atmosphere
      transport (LRAT) processes from Indian subcontinent in the south and Sichuan in
      the east. For the northwest Tibet, the westerly wind originated from the western
      boundaries between India and Nepal but not local emission might play an important
      role in input of PAHs, since there were slight anthropogenic activities. A
      general decrease of ?15-PAHs with depth suggested their atmospheric input, while
      surface runoff might also play an important role in input of PAHs to soils from
      canyon and valley. The abundances of more volatile three-ring PAHs positively
      correlated with altitudes while less volatile ones unrelated (four rings) or
      inversely correlated (five and six rings) with altitudes, indicating cold
      condensation effect. The results of PAH isomer ratios suggested mixed sources of
      petroleum evaporation and combustion of petroleum and biomass.

PMID- 25772871
TI  - Assessing and monitoring the ecotoxicity of pulp and paper wastewater for
      irrigating reed fields using the polyurethane foam unit method based on
      monitoring protozoal communities.
AB  - Using the standardized polyurethane foam unit (PFU) method, a preliminary
      investigation was carried out on the bioaccumulation and the ecotoxic effects of
      the pulp and paper wastewater for irrigating reed fields. Static ectoxicity test
      had shown protozoal communities were very sensitive to variations in toxin time
      and effective concentration (EC) of the pulp and paper wastewater. Shannon-Wiener
      diversity index (H) was a more suitable indicator of the extent of water
      pollution than Gleason and Margalef diversity index (d), Simpson's diversity
      index (D), and Pielou's index (J). The regression equation between S eq and EC
      was S eq  = - 0.118EC + 18.554. The relatively safe concentration and maximum
      acceptable toxicant concentration (MATC) of the wastewater for the protozoal
      communities were about 20 % and 42 %, respectively. To safely use this wastewater
      for irrigation, more than 58 % of the toxins must be removed or diluted by
      further processing. Monitoring of the wastewater in representative irrigated reed
      fields showed that the regularity of the protozoal colonization process was
      similar to the static ectoxicity, indicating that the toxicity of the irrigating
      pulp and paper wastewater was not lethal to protozoal communities in the reed
      fields. This study demonstrated the applicability of the PFU method in monitoring
      the ecotoxic effects of pulp and paper wastewater on the level of microbial
      communities and may guide the supervision and control of pulp and paper
      wastewater irrigating within the reed fields ecological system (RFES).

PMID- 25772872
TI  - Microbial abundance and community in subsurface flow constructed wetland
      microcosms: role of plant presence.
AB  - In this research, the role of plants in improving microorganism growth conditions
      in subsurface flow constructed wetland (CW) microcosms was determined. In
      particular, microbial abundance and community were investigated during summer and
      winter in Phragmites australis-planted CW microcosms (PA) and unplanted CW
      microcosms (control, CT). Results revealed that the removal efficiencies of
      pollutants and microbial community structure varied in winter with variable
      microbial abundance. During summer, PA comprised more dominant phyla (e.g.,
      Proteobacteria, Actinobacteria, and Bacteroidetes), whereas CT contained more
      Cyanobacteria and photosynthetic bacteria. During winter, the abundance of
      Proteobacteria was >40 % in PA but dramatically decreased in CT. Moreover,
      Cyanobacteria and photosynthetic bacterial dominance in CT decreased. In both
      seasons, bacteria were more abundant in root surfaces than in sand. Plant
      presence positively affected microbial abundance and community. The potential
      removal ability of CT, in which Cyanobacteria and photosynthetic bacteria were
      abundant during summer, was more significantly affected by temperature reduction
      than that of PA with plant presence.

PMID- 25772873
TI  - Chemical and plant tests to assess the viability of amendments to reduce metal
      availability in mine soils and tailings.
AB  - The goal of this research was to assess the potential of several industrial
      wastes to immobilise metals in two polluted soils deriving from an old Pb/Zn
      mine. Two different approaches were used to assess the performance of different
      amendments: a chemical one, using extraction by ethylenediaminetetraacetic acid
      (EDTA), and a biological one, using Lupinus albus as a bio-indicator. Four
      amendments were used: inorganic sugar production waste (named 'sugar foam', SF),
      sludge from a drinking water treatment sludge (DWS), organic waste from olive
      mill waste (OMW) and paper mill sludge (PMS). Amendment to soil ratios ranged
      from 0.1 to 0.3 (w/w). All the amendments were capable of significantly
      decreasing (p < 0.05) EDTA-extractable Pb, Zn and Cu concentrations in the two
      soils used, with decreases in ranges 21-100, 25-100 and 2-100 % for Pb, Zn and
      Cu, respectively. The amendments tested were also effective in reducing the
      bioavailability of Pb and Zn for L. albus, which gave rise to a decrease in shoot
      metal accumulation by the lupine plants compared to that found in the control
      soil. That decrease reached up to 5.6 and 2.8 times for Pb and Zn, respectively,
      being statistically significant in most cases. Moreover, application of the OMW,
      DWS and SF amendments led to higher average values of plant biomass (up to 71%)
      than those obtained in the control soil. The results obtained showed the
      technology put forward to be a viable means of remediating mine soils as it led
      to a decrease in the availability and toxicity of metals and, thus, facilitated
      the growth of a vegetation layer.

PMID- 25772874
TI  - Competitive sorption and desorption of trace elements by Tunisian Aridisols
      Calcorthids.
AB  - The sorption and retention processes play an important role in determining the
      bioavaibility and fate of trace elements in soils. Sorption and desorption of
      Pb(2+), Zn(2+), Ni(2+), Cu(2+), and Co(2+) in three Tunisian Aridisols
      Calcorthids (AR1, AR2, and AR3) were studied using batch experiments. Sorption
      and retention capacities were determined by means of K r parameter and they were
      related to soil properties. The results showed that in all studied soils, K r
      values for Pb(2+) and Cu(2+) were higher than those of Zn(2+), Ni(2+), and Co(2+)
      indicating that soils have higher affinity for the first ones. The high sorption
      and retention capacity of the three studied soils is ascribed to their alkaline
      pH and their high carbonates contents favoring the precipitation of these
      elements. Moreover, bivariate correlation analysis showed that sorption and
      retention of the studied cations was also strongly correlated with clay fraction
      and Fe oxides contents. All soils show high sorption irreversibility of Pb(2+),
      Zn(2+), Ni(2+), Cu(2+), and Co(2+). The soils with highest sorption capacity show
      also the highest irreversibility. 

PMID- 25772875
TI  - DO3SE model applicability and O3 flux performance compared to AOT40 for an O3
      sensitive tropical tree species (Psidium guajava L. 'Paluma').
AB  - Phytotoxic ozone (O3) levels have been recorded in the Metropolitan Region of Sao
      Paulo (MRSP). Flux-based critical levels for O3 through stomata have been adopted
      for some northern hemisphere species, showing better accuracy than with
      accumulated ozone exposure above a threshold of 40 ppb (AOT40). In Brazil,
      critical levels for vegetation protection against O3 adverse effects do not
      exist. The study aimed to investigate the applicability of O3 deposition model
      (Deposition of Ozone for Stomatal Exchange (DO3SE)) to an O3-sensitive tropical
      tree species (Psidium guajava L. 'Paluma') under the MRSP environmental
      conditions, which are very unstable, and to assess the performance of O3 flux and
      AOT40 in relation to O3-induced leaf injuries. Stomatal conductance (g s)
      parameterization for 'Paluma' was carried out and used to calculate different
      rate thresholds (from 0 to 5 nmol O3 m(-2) projected leaf area (PLA) s(-1)) for
      the phytotoxic ozone dose (POD). The model performance was assessed through the
      relationship between the measured and modeled g sto. Leaf injuries were analyzed
      and associated with POD and AOT40. The model performance was satisfactory and
      significant (R (2) = 0.56; P < 0.0001; root-mean-square error (RMSE) = 116). As
      already expected, high AOT40 values did not result in high POD values. Although
      high POD values do not always account for more injuries, POD0 showed better
      performance than did AOT40 and other different rate thresholds for POD. Further
      investigation is necessary to improve our model and also to check if there is a
      critical level of ozone in which leaf injuries arise. The conclusion is that the
      DO3SE model for 'Paluma' is applicable in the MRSP as well as in temperate
      regions and may contribute to future directives.

PMID- 25772877
TI  - Effects of mountain beaver management and thinning on 15-year-old Douglas fir
      growth and survival.
AB  - We examined 4-year growth of 15-year-old damaged and undamaged Douglas fir
      (Pseudotsuga menzesii) after integrating temporary population reductions of
      mountain beaver (Aplodontia rufa) with thinning in a pre-commercial hand-planted
      plantation in western Washington. Five treatment combinations were considered:
      (1) trapping mountain beavers in an unthinned area, (2) trapping before thinning
      to 65 trees/ha (160 trees/ac), (3) no trapping and thinning to 65 trees/ha, (4)
      no trapping and thinning to 146 trees/ha (360 trees/ac), and (5) no trapping and
      no thinning. Removal of >= 90 % of mountain beavers temporarily reduced mountain
      beaver activity whether the stand was unthinned or thinned. Diameter growth at
      breast height (dbh) was greater for undamaged trees than for damaged trees in
      thinned areas. Tree height growth was greatest in trapped areas whether thinned
      or not. No differences were detected in 4-year survival between trees damaged
      aboveground and those without aboveground damage, which may be related to
      undetected root damage to trees without aboveground damage. Basal diameter growth
      and dbh growth were greatest for areas thinned to 65 trees/ha. Seventy-eight
      percent of stomachs from mountain beaver trapped in winter contained Douglas fir
      root or stem materials. Overall, short-term removal of mountain beavers
      integrated with pre-commercial thinning promoted growth of crop trees.

PMID- 25772876
TI  - Assessment of Toxoplasma gondii levels in zebra mussel (Dreissena polymorpha) by
      real-time PCR: an organotropism study.
AB  - Water quality is a public health concern that calls for relevant biomonitoring
      programs. Molecular tools such as polymerase chain reaction (PCR) are
      progressively becoming more sensitive and more specific than conventional
      techniques to detect pathogens in environmental samples such as water and
      organisms. The zebra mussel (Dreissena polymorpha) has already been demonstrated
      to accumulate and concentrate various human waterborne pathogens. In this study,
      first, a spiking experiment to evaluate detection levels of Toxoplasma gondii DNA
      in zebra mussel organs using real-time PCR was conducted. Overall, lower DNA
      levels in the hemolymph, digestive gland, and remaining tissues (gonad and foot)
      were detected compared to mantle, muscle, and gills. Second, an in vivo
      experiment with 1000 T. gondii oocysts per mussel and per day for 21 consecutive
      days, followed by 14 days of depuration time in protozoa-free water was
      performed. T. gondii DNA was detected in all organs, but greatest concentrations
      were observed in hemolymph and mantle tissues compared to the others organs at
      the end of the depuration period. These results suggest that (i) the zebra mussel
      is a potential new tool for measuring T. gondii concentrations and (ii) real-time
      PCR is a suitable method for pathogen detection in complex matrices such as
      tissues. 

PMID- 25772878
TI  - Carbonaceous aerosol composition over northern China in spring 2012.
AB  - The organic carbon (OC) and elemental carbon (EC) collected by eight-stage air
      samplers over northern China during spring 2012 were determined to characterize
      the spatial variations, size distributions, and sources of carbonaceous aerosols.
      OC and EC had high concentration levels and spatial heterogeneity. Higher
      carbonaceous aerosol loadings were found in urban areas, and high concentrations
      of OC and EC were found in eastern parts of northern China, including Beijing,
      Taiyuan in Shanxi Province, Yucheng in Shandong Province, Xianghe in Hebei
      Province, and Shenyang in Liaoning Province. Except the Cele site, OC and EC at
      all the sites showed a bimodal distribution, peaking in the size of 0.4-0.7 and
      4.7-5.8 MUm. Carbonaceous aerosols in the fine mode in the urban areas are mostly
      presented in smaller sizes than those in the rural/regional background areas. For
      most sites, mass median aerodynamic diameter (MMAD) values in the fine particles
      for OC were higher than those for EC with the addition of semi-volatile organics.
      Good correlations between OC and EC in all the cities (5 in North China and 1 in
      northeast China) may suggest the impact of anthropogenic emissions on
      carbonaceous aerosols in the above regions.

PMID- 25772879
TI  - The limiting role of oxygen penetration in sediment nitrification.
AB  - Oxygen penetration is a key determinant of sediment nitrification rates. In this
      study, we analyzed the effect of oxygen penetration on the sediment nitrification
      rate based on sediment oxygen profiles. Six sediments were designed to produce
      different oxygen profiles by adding different amounts of silica gel to the
      collected river mud. The oxygen profiles in the sediment were detected using a
      voltammetric microelectrode. With increased mud content, the sediment oxygen
      penetration depth decreased from 8.3 to 2.6 mm, and the oxygen concentration in
      the overlying water and at the sediment-water interface also showed a decreasing
      trend. The measured nitrification rate displayed a quadratic pattern that changed
      with the increase in mud content. Based on the detected oxygen profiles, the
      nitrification rate at each depth was calculated and summed to obtain the bulk
      sediment nitrification rate. The bulk sediment nitrification rate showed a
      consistently changing pattern with the measured rate. Oxygen profiles used to
      calculate nitrification rates could be approximated by the penetration depth
      (delta). The resulting nitrification model based on delta could explain the
      limiting role of oxygen penetration in sediment nitrification.

PMID- 25772880
TI  - DNA-protein cross-links involved in growth inhibition of rice seedlings exposed
      to Ga.
AB  - Hydroponic experiments were conducted with rice seedlings (Oryza sativa L. cv.
      XZX45) exposed to gallium nitrate (Ga(3+)) to investigate the accumulation of Ga
      in plant tissues and phytotoxic responses. Results showed that phyto-transport of
      Ga was apparent, and roots were the dominant site for Ga accumulation. The total
      accumulation rates of Ga responded biphasically to Ga treatments by showing
      increases at low (1.06-8.52 mg Ga/L) and constants at high (8.52-15.63 mg Ga/L)
      concentrations, suggesting that accumulation kinetics of Ga followed a typical
      saturation curve. Higher amount of Ga accumulation in plant tissues led to
      significant inhibition in relative growth rate and water use efficiency in a dose
      dependent manner. DNA-protein cross-links (DPCs) analysis revealed that
      overaccumulation of Ga in plant tissues positively stimulated formation of DPCs
      in roots. Likewise, the measure of root cell viability evaluated by Evan blue
      uptake showed a similar trend. These results suggested that Ga can be absorbed,
      transported, and accumulated in plant materials of rice seedlings.
      Overaccumulation of Ga in plant tissues provoked the formation of DPCs in roots,
      which resulted in cell death and growth inhibition of rice seedlings.

PMID- 25772881
TI  - Potential of acetylacetone as a mediator for Trametes versicolor laccase in
      enzymatic transformation of organic pollutants.
AB  - Low-cost and environmentally friendly mediators could facilitate the application
      of laccase (EC 1.10.3.2) in variant biotechnological processes. Acetylacetone
      (AA) represents an inexpensive and low toxic small molecular diketone that has
      been proven as an effective mediator for laccase in free radical polymerization.
      However, the potential of AA as a mediator for laccase in pollutant
      detoxification and/or degradation is still unknown. In this work, the roles of AA
      in laccase-induced polymerization and transformation were investigated. AA was
      demonstrated to be a highly efficient mediator in the laccase-induced grafting
      copolymerization of acrylamide and chitosan. The efficacy of AA in the laccase
      induced decoloration of malachite green (MG) was compared with that of the widely
      used 1-hydroxybenzotriazole (HBT). The laccase-AA system had the highest turnover
      number (TON, 39.1 MUmol/U), followed by the laccase-only system (28.5 MUmol/U),
      while the TON of the laccase-HBT system was the lowest (14.9 MUmol/U). The pseudo
      first-order transformation rate constant (k 1) of MG in the laccase-AA system was
      up to 0.283 h(-1) under the given conditions, while the k 1 of AA caused by
      laccase was only 0.008 h(-1). In the five-cycle run, the concentration of AA
      remained stable. The larger TON of the laccase-AA system and the stability of AA
      in the cycling runs demonstrate that AA was more recyclable than HBT in the LMS,
      leading to a prolonged serving life of laccase. These results suggest that AA
      might be a potential redox mediator for laccase.

PMID- 25772883
TI  - SUDEP research without walls.

PMID- 25772882
TI  - Analysis of a population of magnetotactic bacteria of the Gulf of Gabes, Tunisia.
AB  - The occurrence of magnetotactic bacteria (MTB) on a Tunisian marine coast exposed
      to heavy metals pollution (Sfax, Gulf of Gabes, Mediterranean Sea) was
      investigated. The MTB population of this Southern Mediterranean coast was
      compared to the MTB populations previously investigated on the French Northern
      Mediterranean coast. A dominant MTB coccus morphotype was observed by microscopy
      analysis. By pyrosequencing technology, the analysis of the 16S ribosomal RNA
      (rDNA) revealed as much as 33 operational taxonomic sequence units (OTUs) close
      to sequences of MTB accessible in the databases. The majority were close to MTB
      sequences of the "Med group" of alpha-Proteobacteria. Among them, a dominant
      OTU_001 (99 % of the MTB sequences) affiliated within the Magnetococcales order
      was highlighted. Investigating the capacities of this novel bacterium to be used
      in bioremediation and/or depollution processes could be envisaged.

PMID- 25772884
TI  - Overcoming barriers in progressive multiple sclerosis research.

PMID- 25772885
TI  - A much-needed focus on progression in multiple sclerosis.

PMID- 25772886
TI  - Corrections.

PMID- 25772887
TI  - Brain banking as a cornerstone of neuroscience in China.

PMID- 25772888
TI  - Orbital compartment syndrome after head trauma.

PMID- 25772889
TI  - Orbital compartment syndrome after head trauma--authors' reply.

PMID- 25772890
TI  - Are we ready for direct-to-consumer genetic testing?

PMID- 25772891
TI  - Hans Lassmann: still determined to solve the puzzle.

PMID- 25772892
TI  - Friedreich's footprint.

PMID- 25772893
TI  - Nadine Attal.

PMID- 25772897
TI  - Pathological mechanisms in progressive multiple sclerosis.
AB  - A better understanding of the pathological mechanisms that drive
      neurodegeneration in individuals with multiple sclerosis is needed to develop
      therapies that will effectively treat patients in the primary and secondary
      progressive stages of the disease. We propose that the inflammatory demyelinating
      disease process in early multiple sclerosis triggers a cascade of events that
      lead to neurodegeneration and are amplified by pathogenic mechanisms related to
      brain ageing and accumulated disease burden. Key elements driving
      neurodegeneration include microglia activation, chronic oxidative injury,
      accumulation of mitochondrial damage in axons, and age-related iron accumulation
      in the human brain. Altered mitochondrial function in axons might be of
      particular importance. This process leads to chronic cell stress and imbalance of
      ionic homoeostasis, resulting in axonal and neuronal death. The evidence suggests
      that treatment of progressive multiple sclerosis should be based on a combination
      of anti-inflammatory, regenerative, and neuroprotective strategies. 

PMID- 25772898
TI  - Treatment of progressive multiple sclerosis: what works, what does not, and what
      is needed.
AB  - Disease-modifying drugs have mostly failed as treatments for progressive multiple
      sclerosis. Management of the disease therefore solely aims to minimise symptoms
      and, if possible, improve function. The degree to which this approach is based on
      empirical data derived from studies of progressive disease or whether treatment
      decisions are based on what is known about relapsing-remitting disease remains
      unclear. Symptoms rated as important by patients with multiple sclerosis include
      balance and mobility impairments, weakness, reduced cardiovascular fitness,
      ataxia, fatigue, bladder dysfunction, spasticity, pain, cognitive deficits,
      depression, and pseudobulbar affect; a comprehensive literature search shows a
      notable paucity of studies devoted solely to these symptoms in progressive
      multiple sclerosis, which translates to few proven therapeutic options in the
      clinic. A new strategy that can be used in future rehabilitation trials is
      therefore needed, with the adoption of approaches that look beyond single
      interventions to concurrent, potentially synergistic, treatments that maximise
      what remains of neural plasticity in patients with progressive multiple
      sclerosis. 

PMID- 25772899
TI  - Clinical trials in progressive multiple sclerosis: lessons learned and future
      perspectives.
AB  - Progressive multiple sclerosis is characterised clinically by the gradual accrual
      of disability independent of relapses and can occur with disease onset (primary
      progressive) or can be preceded by a relapsing disease course (secondary
      progressive). An effective disease-modifying treatment for progressive multiple
      sclerosis has not yet been identified, and so far the results of clinical trials
      have generally been disappointing. Ongoing advances in the knowledge of
      pathogenesis, in the identification of novel targets for neuroprotection, and in
      improved outcome measures could lead to effective treatments for progressive
      multiple sclerosis. In this Series paper, we summarise the lessons learned from
      completed clinical trials and perspectives from trials in progress in progressive
      multiple sclerosis. We review promising clinical, imaging, and biological
      markers, along with novel designs, for clinical trials. The use of more refined
      outcomes and truly neuroprotective drugs, coupled with more efficient trial
      design, has the capacity to deliver a new era of therapeutic discovery in this
      challenging area. 

PMID- 25772900
TI  - Constraint-induced movement therapy after stroke.
AB  - Constraint-induced movement therapy (CIMT) was developed to overcome upper limb
      impairments after stroke and is the most investigated intervention for the
      rehabilitation of patients. Original CIMT includes constraining of the non
      paretic arm and task-oriented training. Modified versions also apply constraining
      of the non-paretic arm, but not as intensive as original CIMT. Behavioural
      strategies are mostly absent for both modified and original CIMT. With forced use
      therapy, only constraining of the non-paretic arm is applied. The original and
      modified types of CIMT have beneficial effects on motor function, arm-hand
      activities, and self-reported arm-hand functioning in daily life, immediately
      after treatment and at long-term follow-up, whereas there is no evidence for the
      efficacy of constraint alone (as used in forced use therapy). The type of CIMT,
      timing, or intensity of practice do not seem to affect patient outcomes. Although
      the underlying mechanisms that drive modified and original CIMT are still poorly
      understood, findings from kinematic studies suggest that improvements are mainly
      based on adaptations through learning to optimise the use of intact end-effectors
      in patients with some voluntary motor control of wrist and finger extensors after
      stroke. 

PMID- 25772903
TI  - Anaesthetic management of transcatheter aortic valve implantation: results from
      the Italian CoreValve registry.
AB  - AIMS: Transcatheter aortic valve implantation (TAVI) represents a valid
      therapeutic alternative for patients with severe aortic stenosis at high surgical
      risk. However, there is no general consensus regarding the role of anaesthesia in
      TAVI management. The goal of this clinical project was to assess the safety and
      non-inferiority of local anaesthesia (LA) versus general anaesthesia (GA) in a
      large cohort of patients undergoing TAVI. METHODS AND RESULTS: All 1,316
      consecutive patients who underwent TAVI at seven high-volume Italian centres were
      enrolled. The anaesthetic regimen consisted of GA in 355 (26.9%) patients or LA
      in 961 (73.0%) patients. Baseline demographics were similar between the two
      groups except for a higher median logistic EuroSCORE (p=0.004) and peripheral
      artery disease (p<0.001) in the GA group. The two groups showed similar device
      success with no significant difference in terms of mortality, stroke and
      myocardial infarction. The overall procedural time was longer with the use of GA
      (p<0.001). The LA group showed a lower incidence of major access-site
      complications (p=0.01) and major (p=0.03) and life-threatening bleedings
      (p<0.001) with a lower occurrence of acute kidney injury stage 3 (p=0.002).
      Consistently, we observed a significantly shorter length of hospital stay in LA
      patients (8 days [7-13] vs. 7 days [6-10], GA vs. LA; p<0.001). As the GA
      patients were found to be at higher risk due to a higher prevalence of peripheral
      artery disease we carried out a propensity matching to obtain two comparable
      groups. This sub-analysis confirmed the same results previously observed in the
      overall population. As expected, in the GA group we observed longer procedural
      time, higher use of a surgical vascular access, higher incidence of acute kidney
      injury stage 3 and higher rate of bleeding and major vascular access-site
      complications. CONCLUSIONS: Our study indicates that, in experienced centres
      which have gone beyond their initial learning curve with TAVI, the use of local
      anaesthesia in a selected patient population can be associated with good clinical
      outcomes. Nevertheless, as severe procedural complications are possible, an
      anaesthesiologist should always be present as part of the team.

PMID- 25772902
TI  - Evaluation of aortic regurgitation after transcatheter aortic valve implantation:
      aortic root angiography in comparison to cardiac magnetic resonance.
AB  - AIMS: Aortic regurgitation (AR) is common after transcatheter aortic valve
      implantation (TAVI). Intraprocedural assessment of AR relies on aortic root
      angiography. Cardiac magnetic resonance (CMR) phase-contrast mapping of the
      ascending aorta provides accurate AR quantification. This study evaluated the
      accuracy of AR grading by aortic root angiography after TAVI in comparison to CMR
      phase-contrast velocity mapping. METHODS AND RESULTS: In 69 patients with TAVI
      for severe aortic stenosis, post-procedural AR was determined by aortic root
      angiography with visual assessment according to the Sellers classification and by
      CMR using phase-contrast velocity mapping for analysis of AR volume and fraction.
      Spearman's correlation coefficient showed a moderate correlation between
      angiographic analysis of AR grade and CMR-derived AR volume (r=0.41; p<0.01) as
      well as AR fraction (r=0.42; p<0.01). There was significant overlap between the
      angiographic Sellers classes compared to CMR-derived AR fractions. Aortic root
      angiography with cut-off Sellers grade >=2 had a sensitivity of 71% and a
      specificity of 98% to detect AR graded as moderate to severe or severe as defined
      by CMR. CONCLUSIONS: There is only a moderate correlation between aortic root
      angiography and CMR in the classification of AR severity after TAVI. Alternative
      imaging including multimodality imaging as well as haemodynamic analysis should
      therefore be considered for intraprocedural AR assessment and guidance of TAVI
      procedure in cases of uncertainty in AR grading.

PMID- 25772901
TI  - Bisphenol-A affects male fertility via fertility-related proteins in spermatozoa.
AB  - The xenoestrogen bisphenol-A (BPA) is a widespread environmental contaminant that
      has been studied for its impact on male fertility in several species of animals
      and humans. Growing evidence suggests that xenoestrogens can bind to receptors on
      spermatozoa and thus alter sperm function. The objective of the study was to
      investigate the effects of varying concentrations of BPA (0.0001, 0.01, 1, and
      100 MUM for 6 h) on sperm function, fertilization, embryonic development, and on
      selected fertility-related proteins in spermatozoa. Our results showed that high
      concentrations of BPA inhibited sperm motility and motion kinematics by
      significantly decreasing ATP levels in spermatozoa. High BPA concentrations also
      increased the phosphorylation of tyrosine residues on sperm proteins involved in
      protein kinase A-dependent regulation and induced a precocious acrosome reaction,
      which resulted in poor fertilization and compromised embryonic development. In
      addition, BPA induced the down-regulation of beta-actin and up-regulated
      peroxiredoxin-5, glutathione peroxidase 4, glyceraldehyde-3-phosphate
      dehydrogenase, and succinate dehydrogenase. Our results suggest that high
      concentrations of BPA alter sperm function, fertilization, and embryonic
      development via regulation and/or phosphorylation of fertility-related proteins
      in spermatozoa. We conclude that BPA-induced changes in fertility-related protein
      levels in spermatozoa may be provided a potential cue of BPA-mediated disease
      conditions.

PMID- 25772904
TI  - Proof of concept of FOLDAVALVE, a novel 14 Fr totally repositionable and
      retrievable transcatheter aortic valve.
AB  - AIMS: Transcatheter aortic valve implantation (TAVI) is an emerging field with
      technological challenges. One major challenge is to minimise delivery catheter
      size to reduce vascular trauma, while maintaining features such as
      repositionability and retrievability. This study was designed as proof of concept
      of FOLDAVALVE, using a short-term ovine model. METHODS AND RESULTS: FOLDAVALVE is
      a fully repositionable and retrievable transcatheter aortic valve with a 14 Fr
      delivery system whose leaflets are excluded from the stent during crimping. A
      short-term ovine model (n=3) was used for transfemoral implantations at the
      Institut Mutualiste Montsouris in Paris. There was a smooth transition of the
      valve over the aortic arch followed by seamless delivery into the native ovine
      aortic position. Implantation was followed by repositioning, resheathing and
      retrieval, then implantation of a fresh prosthesis in the same animal.
      Transoesophageal echocardiography and fluoroscopy were used to monitor the
      delivery and implantation processes and to demonstrate valve functionality.
      Animal sacrifice and direct visualisation after explant confirmed excellent final
      position. CONCLUSIONS: FOLDAVALVE was successfully implanted in the aortic
      position of an ovine model. FOLDAVALVE is a promising technology which has been
      shown to be feasible in this preclinical TAVI study.

PMID- 25772905
TI  - Gluing together metallic and covalent layers to form Ru2C under ambient
      conditions.
AB  - Ru2C has recently been synthesised at high pressure and high temperature, and was
      assumed to have a structure with space group P3m1. However, subsequent
      theoretical work has revealed that this structure is unstable under ambient
      conditions, which motivated us to look for the stable structure. In this work, we
      explore the structures of Ru2C by using an unbiased swarm structure searching
      algorithm. The structures with R3m and R3m symmetries have been found to be lower
      in energy than the P3m1 structure, at the same time being dynamically stable
      under ambient conditions. These layered structures consist of alternating Ru
      bilayers and C monolayers in the R3m structure, and alternating Ru tetra-layers
      and C bilayers in the R3m structure. The C layers are more evenly distributed and
      more covalently bound to the Ru layers in the R3m structure than in the R3m
      structure. Instead, in the R3m structure there exists more Ru-Ru metallic
      bonding, which has a crucial role in diminishing the hardness of this material.
      Our findings should stimulate further explorations of the structures and
      properties of the heavy transition metal carbides and nitrides, potentially
      leading to industrial applications.

PMID- 25772906
TI  - Pathways to a lung cancer diagnosis.
AB  - PURPOSE: The purpose of this qualitative descriptive study was to identify and
      describe pathways to a lung cancer diagnosis based on narratives of persons
      diagnosed with the disease. DATA SOURCES: Eleven adults with lung cancer were
      recruited from an academic thoracic oncology clinic in a large city in the
      southeastern United States. Moderately structured interviews were conducted by an
      experienced nurse practitioner (NP) to obtain information regarding the
      participants' experiences leading to their diagnosis. Qualitative content
      analysis was used to develop a typology of pathways. CONCLUSIONS: Findings
      revealed four distinct pathways: missing opportunities, waiting and seeing, being
      alarmed, and being blindsided. IMPLICATIONS FOR PRACTICE: The Pathways to a Lung
      Cancer Diagnosis Typology has important implications for clinical practice and
      can be used to inform NPs and other healthcare providers who provide care for
      patients at risk for or diagnosed with lung cancer.

PMID- 25772908
TI  - Ingrown nail with a giant granulation tissue successfully treated with the gutter
      method.

PMID- 25772907
TI  - Dietary docosahexaenoic acid supplementation reduces SERCA Ca2+ transport
      efficiency in rat skeletal muscle.
AB  - Docosahexaenoic acid (DHA) can reduce the efficiency and increase the energy
      consumption of Na(+)/K(+)-ATPase pump and mitochondrial electron transport chain
      by promoting Na(+) and H(+) membrane permeability, respectively. In skeletal
      muscle, the sarco(endo) plasmic reticulum Ca(2+)-ATPase (SERCA) pumps are major
      contributors to resting metabolic rate. Whether DHA can affect SERCA efficiency
      remains unknown. Here, we examined the hypothesis that dietary supplementation
      with DHA would reduce Ca(2+) transport efficiency of the SERCA pumps in skeletal
      muscle. Total lipids were extracted from enriched sarcoplasmic reticulum (SR)
      membranes that were isolated from red vastus lateralis skeletal muscles of rats
      that were either fed a standard chow diet supplemented with soybean oil or
      supplemented with DHA for 8 weeks. The fatty acid composition of total SR
      membrane lipids and the major phospholipid species were determined using
      electrospray ionization mass spectrometry (ESI-MS). After 8 weeks of DHA
      supplementation, total SR DHA content was significantly elevated (control, 4.1 +/
      1.0% vs. DHA, 9.9 +/- 1.7%; weight percent of total fatty acids) while total
      arachidonic acid was reduced (control, 13.5 +/- 0.4% vs. DHA-fed, 9.4 +/- 0.2).
      Similar changes in these fatty acids were observed in phosphatidylcholine,
      phosphatidylethanolamine, and phosphatidylinositol, altogether indicating
      successful incorporation of DHA into the SR membranes post-diet. As hypothesized,
      DHA supplementation reduced SERCA Ca(2+) transport efficiency (control, 0.018 +/-
      0.0002 vs. DHA-fed, 0.014 +/- 0.0009) possibly through enhanced SR Ca(2+)
      permeability (ionophore ratio: control, 2.8 +/- 0.2 vs. DHA-fed, 2.2 +/- 0.3).
      Collectively, our results suggest that DHA may promote skeletal muscle-based
      metabolism and thermogenesis through its influence on SERCA.

PMID- 25772909
TI  - Immunization status of internationally adopted children in Rome, Italy.
AB  - AIMS: International adoption medicine is a relatively new specialty in pediatrics
      that has emerged to address the specific health care needs of internationally
      adopted children in high-income countries. This study ascertains the
      seroprotection rate for vaccine-preventable diseases, especially against
      pneumococcal diseases. PATIENTS AND METHODS: We evaluated 67 internationally
      adopted children that reached the International Adoption Unit of Bambino Gesu
      Children's Hospital, Rome-Italy. We collected demographic information, data from
      preadoption immunization records, results of laboratory testing for immunity to
      vaccine-preventable diseases (tetanus, pneumococcus, hepatitis B, hemophilus
      influenzae type b (Hib), measles), as well as results of screening for HIV,
      hepatitis C, quantiferon, immunological and nutritional status. RESULTS: For
      children that had received >=3 vaccine doses of tetanus, overall protection was
      94% of 31 vaccinated children; with 1-2 vaccine doses for hepatitis B and Hib
      respectively, protection was 45% of 29 vaccinated children and 63% of 8
      vaccinated children, respectively. For children with one or more doses of measles
      vaccine, protection was 63% of 32 vaccinated children. Regarding pneumococcus
      vaccine (documented for eight children), 88% of children with one or more doses
      of vaccine had developed protective immunity. CONCLUSIONS: International adoptees
      without a valid vaccine record need to undergo a complete schedule in accordance
      with their age and should receive all the vaccines in the adoptive country's
      schedule.

PMID- 25772910
TI  - Knowledge and attitude of dentists toward implant retained restorations in Saudi
      Arabia.
AB  - OBJECTIVES: The aim was to assess the knowledge and attitudes of specialists (SP)
      and general dental practitioners (GDP) toward cement-retained restoration (CRR),
      screw-retained restoration (SRR) and implant restorations in Saudi Arabia.
      MATERIALS AND METHODS: Self-designed-structured questionnaires were distributed
      between SP and GDP by hand and through E-mails. Opinion of dentists regarding
      factors vital in selection of CRR and SRR was enquired. Factors included
      esthetics, retrievability, retention, passive fit, fracture resistance, tissue
      health, cost-effectiveness, fabrication ease, and required expertise.
      Participants also graded significance of treatment-planning factors for implant
      retained prosthesis. Analysis of comparative response frequencies and
      significance grades was done using the Chi-square and independent t-test.
      RESULTS: Of 552 respondents, 64% were SP and 36% were GDP with overall response
      rate of 67%. About 75% of SP and 80% of GDP used SRR in <50% and <25% of their
      implant practice respectively. The opinion of GDP and SP was significantly
      different with regards to esthetics, fabrication ease, retrievability, retention
      and cost-effectiveness between CRR and SRR ( P < 0.05). Overall, CRR were
      considered better in terms of esthetics, passive fit, fabrication ease, required
      expertise and fracture resistance. However, SRR were regarded as having better
      retention, retrievability, soft tissue health and cost-effectiveness. The average
      significance scores were significantly higher for SP as compared to GDP for six
      out of nine factors. CONCLUSIONS: Knowledge of SP and GDP for selection of
      implant-retained restorations was broadly in line with standard evidence. The
      clinical use of CRR was greater in comparison to SRR.

PMID- 25772911
TI  - Efficacy of endoscopic third ventriculostomy in the management of hydrocephalus
      in children under 2 years of age: experience from a tertiary institution in
      Nigeria.
AB  - BACKGROUND: The management of hydrocephalus in developing countries is
      challenging. Hydrocephalus is a common childhood disorder in developing countries
      in particular and its management is quite challenging. Ventriculoperitoneal (VP)
      shunt is associated with high failure rates and complications. Endoscopic third
      ventriculostomy (ETV) with potentially lower complication rate could improve care
      and reduce cost of management of hydrocephalus. OBJECTIVE: The aim of this study
      was to evaluate the efficacy (success rate) of ETV in children <=2 years and to
      find out factors that may be responsible for good outcome of ETV. METHODS: This
      prospective observational study was conducted at Lagos University Teaching
      Hospital, Lagos. Nigeria. All consecutive children <=2 years of age with
      hydrocephalus were recruited into the study. Relevant demographic and clinical
      data documented. All cases had ETV and were followed up to document 6 months
      outcome. RESULTS: A total of 34 patients (M: F ratio 1.1:1) were recruited over a
      2-year period. Age, sex, presumed aetiology and image findings were not
      statistically significant in influencing outcome of ETV. Good outcome (defined as
      uneventful postoperative period, not requiring repeat ETV or VP shunt) was
      documented in 26 (73.5%). A total of 8 (26.5%) experienced poor outcome.
      Complication occurred in 2 (5.9%) as follows: Wound infection 1 (2.9%) and
      ventriculitis 1 (2.9%). Aetiology was divided into non post-infective
      hydrocephalus-20 (58.8%), post-infective hydrocephalus-5 (14.7%) and post
      myelomeningocoele repair-9 (26.5%). CONCLUSIONS: This study shows that ETV
      success rate is high in the management of hydrocephalus in children <=2 years in
      our clinical practice. Regardless of the clinical diagnosis, where the facilities
      are available, children with hydrocephalus will benefit from ETV irrespective of
      the age and aetiology in sub Saharan Africa.

PMID- 25772912
TI  - Does antenatal care attendance prevent anemia in pregnancy at term?
AB  - BACKGROUND: Anemia in pregnancy is one of the public health problems in the
      developed and developing world. If uncontrolled it is a major indirect cause of
      maternal and perinatal morbidity and mortality. This is worst in settings with
      poor prenatal practices. Quality prenatal interventions therefore are expected to
      prevent or ameliorate this disorder in pregnancy. Nigerian scientific literatures
      are full of data on anemia in pregnancy, but few of them are on the influence of
      prenatal care on maternal anemia. This study, therefore, sought to appraise the
      role of antenatal care (ANC) services in the prevention of anemia in pregnancy at
      term in Nigerian women. OBJECTIVES: The aim was to estimate the prevalence of
      anemia at first antenatal visit and determine if antenatal attendance prevents
      anemia at term among prenatal Nigerian women. To measure the hematocrit levels at
      booking and at term respectively and compare the proportion anemic at booking
      with the proportion anemic at term. MATERIALS AND METHODS: A retrospective cross
      sectional comparative study of 3442 prenatal women in a mission hospital in South
      South Nigeria from 2009 to 2013. Venous blood hematocrit was estimated from each
      woman at booking and at term, and the prevalence of anemia for the two periods
      were compared. RESULTS: There were 1205 subjects with hematocrit of below 33% at
      booking, an anemia prevalence of 32.2% at booking in this population. At term or
      delivery at term 736 (21.4% odds ratio [OR] =2.3, P < 0.0001) of the 1052
      subjects that fulfilled the study criteria had their anemia corrected, a 69.9%
      prevention, while 316 (9.2%, OR = 0.43, P < 0.0001) persisted despite their
      antenatal attendance. The subjects were similar in most of the confounding
      factors like parity, social class, mean age, body mass index and gestational age
      at delivery (P value: all > 0.05). CONCLUSION: The prevalence of anemia in
      pregnancy is still high in our setting. Quality ANC appeared a valuable
      preventive intervention that should be made widely available, accessible and
      affordable to all pregnant women.

PMID- 25772913
TI  - Prevalence of anti-A and anti-B hemolysis among blood group O donors in Lagos.
AB  - BACKGROUND: Group O donor blood is more readily available and is frequently used
      as universal red cell donor in our environment. The presence of hemolysins in the
      donors may however lead to hemolysis in the recipients. Attempts have been made
      to study the prevalence of hemolysins in various populations with results from
      our environment showing wide variation (20-80%). AIMS: To determine the
      prevalence and titer of anti-A and anti B hemolysins among blood donors at the
      Lagos University Teaching Hospital and compare results with that obtained
      elsewhere. Determine if the practice of transfusion of group O blood to nongroup
      O recipients is permissible in this environment. MATERIALS AND METHODS: Test for
      hemolysis was done using the standard tube method. Samples positive for hemolysis
      were then scored and titrated with the titers read visually and photometrically
      at 540 nm. RESULTS: Three hundred and fifty blood group O donors with age range
      18-58 years and median age of 28 ? 8.4 years were enrolled in the study. The
      overall prevalence of anti-A and/or anti-B hemolysins obtained was 30.3%.
      Prevalence of anti-A and anti-B hemolysins only was 15.4% and 5.1% respectively
      whereas both anti-A and anti-B hemolysins were present in 9.7% donor samples.
      Though anti-A hemolysins were more prevalent than anti-B hemolysins, anti-B
      hemolysins had higher mean visual (6:7) and spectrophotometric titers (81:101). A
      visual titer of 8 and above which is considered significant was seen in 18.6% of
      donor samples. CONCLUSION: Anti-A and anti-B hemolysins exist in significant
      frequencies and titers among blood group O donors in Lagos. It is recommended
      that the use of group O donor blood for recipients who are non-O be discouraged.
      Clinical studies to determine the frequency and severity of hemolysis in non
      group O recipients of blood group O are required.

PMID- 25772914
TI  - Eliminating the barriers to uptake of cataract surgery in a resource-poor
      setting: a focus on direct surgical cost.
AB  - BACKGROUND: Cataract remains a leading cause of blindness worldwide. Despite the
      high therapeutic efficacy of cataract surgical interventions, surgical uptake has
      been sub-optimal, especially in low- and middle-income countries. OBJECTIVE: The
      objective was to investigate the effect of surgical fee reduction on the uptake
      of cataract surgical services at the University of Nigeria Teaching Hospital
      (UNTH) Enugu. METHODS: In a retrospective comparative study, all patients who
      underwent cataract surgery at UNTH between January 2008 and December 2011 were
      identified from the eye theatre's surgical logbook. Their clinical charts were
      recalled and relevant demographic and clinical data were abstracted, categorized
      into pre (January 2008 to December 2009, Group A), and post (January 2010 to
      December 2011, Group B) surgical fee reduction groups. Descriptive and
      comparative statistical analyses were performed. RESULTS: A total of 376 cataract
      surgeries (Group A, 164 [43.6%]; Group B, 212 [56.4%]) was performed during the 4
      year study period. The surgeries were performed on 217 males, and 159 females
      aged 55.4 ? 23.4 standard deviation years (range, 7 months to 89 years). The
      average annual uptake of cataract surgery was 94 overall, 82 pre and 106
      postsurgical fee reductions. The two groups did not differ significantly by age
      (P = 0.8750) or gender (P = 0.8337). CONCLUSION: There is low uptake of cataract
      surgery at UNTH Enugu. Direct surgical fee reduction alone caused only a modest
      increase in uptake without alteration in age and gender balance. Further fee
      reduction and exploration of other uptake barriers are warranted.

PMID- 25772915
TI  - Self-reported sleep parameters among secondary school teenagers in middle-belt
      Nigeria.
AB  - BACKGROUND: Available evidences seem to suggest increasing trend in sleep deficit
      among teenagers worldwide, and there is limited information on this among
      Nigerian teenagers. This study was carried out to determine the basic sleep
      schedule and sleep duration among schooling teenagers in Ilorin, Nigeria.
      METHODS: This is a descriptive cross-sectional study conducted among 20 selected
      public secondary schools in Ilorin, Nigeria. A multistage sampling technique was
      used to randomly select participating schools. RESULT: A total of 1033 students
      participated in the study; of these 47.3% were males and 51.7% females. Students
      mean age (standard deviation) was 15.3 +/- 1.6 years with a range of 12-19 years.
      Majority (76.2%) of participants co-share bed with at least one person and some
      (23.8%) slept alone in bed. The three leading reasons given for going to bed
      were: Tiredness - 31.1%, completion of house assignment - 20.5%, and parental
      directive - 12.4%. 10% of teenagers do make regular phone calls at night and 5.5%
      surf internet and use computers at night. Regular habits of daytime sleepiness
      were reported by 8.2% of study participants. Students' mean sleep duration during
      school days was 9.33 +/- 2.29 h compared to 10.09 +/- 1.32 h at weekend (P <
      0.05). The duration of night time sleep was adequate (>9 h) in 41% of students;
      borderline (8-9 h) in 44.3% while 13.3% of the students had insufficient
      nighttime sleep duration (<8 h) P < 0.05. CONCLUSION: A substantial number of
      students had borderline nighttime sleep duration and so had potentials to transit
      into the problematic insufficient range. To prevent this, there is a need to
      educate schooling teenagers on the dangers associated with prolonged sleep
      insufficiency.

PMID- 25772916
TI  - Prevalence of depression among health workers in Enugu, South East Nigeria.
AB  - AIMS: Determination of the prevalence and distribution of depression among health
      workers at tertiary level of health care delivery in Enugu South East Nigeria.
      SETTINGS AND DESIGN: A cross-sectional descriptive survey of depression in health
      workers at tertiary level. SUBJECTS AND METHODS: By proportional quota sampling,
      the sample size of 309 was used. Ethical issues were given full consideration. A
      structured self-administered questionnaire including the Zung self-rating
      depression scale was used to collect data. STATISTICAL ANALYSIS USED: Data entry
      and analysis were done using SPSS statistical package version 15. Statistical
      significance was considered present when P < 0.05. RESULTS: The total of 46 of
      the 309 workers (14.9%) were found to be depressed. Of the health workers found
      to be depressed, there were more females (18.0%) than males (8.7%). A feeling of
      sadness over family, living and working conditions was more consistent among the
      depressed. CONCLUSIONS: The condition of depression is present among health
      workers in this part of the world. Being a female health worker, may be
      associated with depression in South East Nigeria. Studies to investigate the
      determinants and effects of depression in the Nigerian health work force are
      necessary.

PMID- 25772917
TI  - Pattern and outcome of postneonatal pediatric emergencies in Nnamdi Azikiwe
      University Teaching Hospital, Nnewi, South East Nigeria.
AB  - BACKGROUND: Nigeria is still battling with preventable childhood deaths, being
      one of the six countries in which 50% of all global child deaths occur. Regular
      community and health facility audits are needed to determine morbidity and
      mortality patterns in children which will guide preventive and therapeutic
      interventions. OBJECTIVES: The objective was to determine morbidity and mortality
      patterns, and identify factors influencing poor outcome of the disease in
      children seen in the emergency room of Nnamdi Azikiwe University Teaching
      Hospital, Nnewi. MATERIALS AND METHODS: This was a 2-year retrospective study
      (March 2012 to February 2014) involving all children admitted into the children
      emergency room (CHER). Information on the patients' biodata, diagnosis, and
      outcome were retrieved from the CHER doctors' log. Analysis was done using
      Microsoft Office Excel 2007 and Statistical Package for Social Sciences version
      20. RESULTS: The total of 1964 patients were seen (1088 males, 845 females, 31
      unspecified) with a male to female ratio of 1.3:1. Under-fives constituted 78.8%
      of the study population. Mean duration of illness before presentation was 18.71
      +/- 71.94 days. Malaria, diarrheal disease, and respiratory tract infections were
      the most common morbidities. Sepsis had the highest case fatality rate (CFR) and
      was the most common cause of death among the 247 patients that died - mortality
      rate of 12.6%. Most deaths were in under-fives (CFR = 13.9, chi2 = 25.553, P =
      0.000), with 74.1% of the mortalities occurring within 24 h of presentation.
      Patients who presented within a day and those that presented in the 2 nd and 3 rd
      weeks of onset of symptoms had CFR of 6.4-15.2%, respectively. CONCLUSION:
      Infectious diseases remain a menace in our environment with the eventual outcome
      worsened by late presentation to an appropriate health facility. There is an
      urgent need to create public awareness on the need to seek prompt medical
      attention for sick children.

PMID- 25772918
TI  - Prevalence of Mycoplasma pneumoniae: a cause for community-acquired infection
      among pediatric populaztion.
AB  - BACKGROUND: Atypical pneumonia caused by Mycoplasma pneumoniae is a leading cause
      of mortality among the pediatric age group. OBJECTIVES: Our study was designed to
      know the prevalence of M. pneumoniae in children with community-acquired
      pneumonia and the involvement in the cytoadherence to the respiratory epithelium
      by M. pneumoniae using electron microscopy and immuno-gold labeling technique.
      MATERIALS AND METHODS: A total of 152 children of 1 month to 12 years of age of
      both sexes attending Hebei Provincial People's Hospital, Shijiazhuang, Hebei with
      diagnosed pneumonia were included in the study. RESULTS: Out of 152 children 84
      (55.3%) were males, and 68 (44.7%) were females. The mean age of the patients in
      the control group (50 patients) was 18.5 +/- 3 months with 31 (62%) males and 19
      (38%) females. IgM antibodies against M. pneumoniae were positive in 84 (55.3%)
      males and 68 (44.7%) females. Out of 50 patients 9 (18%) were found to positive
      for IgM M. pneumoniae antibodies of which four (44.4%) males and 5 (55.5%)
      females were positive. Our study observed that the gold particles were clustered
      on the filamentous extension of the tip of the cells. Out of 152 serum samples
      subjected to particle agglutination assay 138 (90.7%) were positive 1:320 titer,
      9 were >1:80 and 3 showed titer was >1:40. CONCLUSION: We suggest that clinicians
      should consider empirical therapy of broad spectrum antibiotics therapy to cover
      these atypical pathogens to reduce the severity before obtaining the serological
      results. From our study, we also suggest electron microscopic and biochemical
      studies for better diagnosis of these pathogens.

PMID- 25772919
TI  - Comparison of various current electronic apex locators to determine the working
      length using the clearing technique.
AB  - BACKGROUND: Correct working length determination is an important step for
      successful endodontic therapy. OBJECTIVE: The objective was to compare in vitro
      the accuracy of three electronic apex locators (EALs) (DentaPort ZX [Morita Co.,
      Tokyo, Japan], SIROEndo Pocket [Sirona Dental Systems, NY, USA], and Rootor [Meta
      Biomed, Cheongwon-gun, Korea]) in detecting the major foramen using the clearing
      technique. MATERIALS AND METHODS: Forty-five human extracted single-rooted teeth
      with mature apices were used for the study and divided into three groups of 15
      teeth each. All teeth were embedded in an alginate model, and the electronic
      measurements were taken following the manufacturers' orientations. Then, the
      teeth were cleared and photographed under a stereomicroscope with a digital
      camera. The distance from the file tip to the major foramen was measured using
      image analysis software program. Statistical analysis was performed using the
      Kruskal-Wallis, Mann-Whitney U, and Chi-square tests at a significance level of
      0.05. RESULTS: The mean distances from the file tip to the major foramen were
      0.164 +/- 0.292, -0.162 +/- 0.234, 0.341 +/- 0.166 mm in the DentaPort ZX,
      SIROEndo Pocket, and Rootor groups, respectively. Statistical analysis showed
      that there was a significant difference between SIROEndo Pocket and Rootor (P <
      0.05). However, no significant difference was found between DentaPort ZX and
      other EALs (P > 0.05). CONCLUSION: DentaPort ZX located the major foramen with
      100% accuracy within the range of +/- 0.5 mm. However, the accuracy of the
      SIROEndo Pocket and Rootor in locating the major foramen within +/- 0.5 mm was
      73.3% and 86.7%, respectively. All EALs showed an acceptable determination of the
      major foramen within the range of +/- 0.5 mm.

PMID- 25772920
TI  - Effect of a re-wetting agent on bond strength of an adhesive to primary and
      permanent teeth dentin after different etching techniques.
AB  - OBJECTIVE: This study investigated the effect of a re-wetting agent on the
      microtensile bond strengths (mTBS) of primary and permanent dentin after acid or
      laser etching. MATERIALS AND METHODS: Twelve permanent and 12 primary molar teeth
      were ground to expose an occlusal dentin surface. Each group teeth were randomly
      divided into groups; I-II: 37% phosphoric acid etching with/without re-wetting
      agent, III-IV: Erbium: Yttrium aluminium garnet laser etching with/without re
      wetting agent. An etch-and-rinse adhesive was used, and vertical sticks were
      obtained for the microtensile test. RESULTS: mTBS of permanent teeth was higher
      than that of primary teeth (P < 0.05). Re-wetting agent groups were similar with
      control groups in both etching groups in the permanent teeth (P > 0.05). Re
      wetting agent group was similar with the control group in acid etch group (P >
      0.05) and lower than the control group in laser etch group in primary teeth (P <
      0.05). CONCLUSION: Acid etching in permanent teeth; laser etching in primary
      teeth was found more successful. The use of re-wetting agent did not provide an
      advance on bond strength of the adhesive in both primary and permanent teeth
      after acid-etch or laser-etch.

PMID- 25772921
TI  - Medication compliance behavior in psychiatric out-patients with psychoactive
      substance use comorbidity in a Nigerian tertiary hospital.
AB  - BACKGROUND: Psychotropic medication adherence is a major challenge in psychiatric
      patients with comorbidity. OBJECTIVE: The objective was to determine medication
      adherence behavior among psychiatric out-patients with psychoactive substance use
      comorbidity in a Nigerian Tertiary Hospital. SETTINGS AND DESIGN: A cross
      sectional study of a tertiary hospital in Northern Nigeria. METHODS: Adult
      patients who have been attending the out-patient clinic for at least 1 year were
      included. From the routine clinic, each consecutive fourth patient completed a
      socio-demographic and drug use questionnaire, a self-administered medication
      adherence scale, and a semi-structured proforma which sought reasons for poor
      adherence, information on supervision and who keeps patient medications at home;
      until a calculated sample of 208 was attained. STATISTICAL ANALYSIS: Done by
      means of descriptive statistics using the Statistical Package for Social Sciences
      version 16. The level of significance was set at P < 0.05. RESULTS: Totally, 208
      patients participated in the study. 61 (29.3%) of them were substance users, out
      of which 59% never reported missing their medications. No statistically
      significant relationship was found between substance use and medication
      adherence. A significant proportion of substance users were compliant with
      medication use when the drugs were in their possession. For substance users and
      nonusers, the major reason for poor drug adherence was the unavailability of the
      medications, while nonsubstance users were more likely to complain about being
      tired of the medications. No report of side effects in supervised patients.
      CONCLUSION: The use of psychoactive substances in patients with other mental
      disorders influences their medication adherence behavior.

PMID- 25772922
TI  - Relationship between 1,25-dihydroxy Vitamin D levels and homeostatic model
      assessment insulin resistance values in obese subjects.
AB  - AIM: In this study, our aim is to evaluate the insulin resistance and quality of
      life in obese subjects and nonobese subjects and to find out the Vitamin D (VD)
      status and correlations between obesity and control groups and also according to
      their quality of life scores. MATERIALS AND METHOD: The study was carried out
      between May and October 2013 which is the period of VD synthesis in Turkey. The
      participants of this study were volunteering individuals - obese and nonobese
      individuals defined according to the body mass index (BMI) - that did not receive
      any VD support in the last 1-year and did not have any known chronic diseases.
      1,25-OH VD status and homeostatic model assessment insulin resistance (HOMA-IR)
      values were evaluated. RESULTS: The study population consisted of 39 individuals
      with normal weight (23 women, 16 men) and 66 individuals categorized as obese (51
      women, 15 men). The difference in HOMA-IR and VD values between the group of
      obese individuals and the group of nonobese individuals was significant (P <
      0.001 vs. P <0.001). The median value of HOMA-IR was higher in the obese group
      than in the nonobese group (P < 0.001) while the median value of VD was higher in
      the nonobese group than in the obese group (P < 0.001). The results regarding the
      relationship of BMI with HOMA-IR and VD show that there was a positive
      correlation between HOMA-IR and BMI (rs = 0.507; P < 0.001) and there was a
      negative correlation between HOMA-IR and VD (rs = -0.316; P = 0.0001).
      CONCLUSION: Given serious diseases associated with low serum VD levels such as
      diabetes and cardiovascular disorders as well as low side effect incidence and
      low cost of VD treatment, it would be a reasonable approach to identify routine
      serum 25(OH) D and/or 1,25-OH VD levels of obese patients and administer a
      treatment to patients with low levels of VD.

PMID- 25772923
TI  - Clinicopathological comparison of triple negative breast cancers with non-triple
      negative breast cancers in a hospital in North India.
AB  - INTRODUCTION: Breast cancer is the second most common cancer worldwide (1.3
      million cases, 10.9%) and ranks 5 th as cause of death from cancer overall
      (458,000 cases, 6.1%). Triple-negative breast cancer (TNBC) is a subtype of
      breast cancer with characteristic biological and pathological features. Among the
      subgroups of breast cancer, triple negative cancer is particularly feared because
      it is associated with poor outcome. However, clinical data on TNBC in Asian
      population are limited. The present study was aimed to find the prevalence of
      TNBCs and to compare various clinicopathological features of TNBC with non TNBC
      patients in our population. MATERIALS AND METHODS: Clinical and pathological data
      of 180 breast cancer patients who visited our department from January 2009 to
      December 2013 were analyzed. Statistical analysis was done using the Chi-square
      test and Mann-Whitney U-test. RESULTS: Of 180 cases, 62 (34.4%) had TNBC. Data
      analysis revealed significant difference in mean age, mean tumor size, tumor
      grade between TNBC and non-TNBC patients. Axillary lymph node metastasis and
      lymphovascular involvement were also more in TNBC patients however this was not
      statistically significant. Extranodal spread was recorded more in non-TNBC
      patients as compared to TNBC patients, but the results were statistically
      insignificant. CONCLUSION: Triple negative breast cancer represented 34.4% which
      is higher than the range normally reported in the literature. TNBC are associated
      with younger age, large tumor size, high-grade tumors, and a higher rate of
      axillary lymph node metastasis.

PMID- 25772924
TI  - Item analysis and evaluation in the examinations in the faculty of medicine at
      Ondokuz Mayis University.
AB  - BACKGROUND: Item analysis is an effective method in the evaluation of multiple
      choice achievement tests. This study aimed to compare the classical and the
      latent class models used in item analysis, as well as their efficacy in the
      evaluation of the examinations of the medical faculty. MATERIALS AND METHODS: The
      achievement tests in the medical faculty were evaluated using different methods.
      The two methods used were the classical and the latent class models. Among the
      classical methods, Cronbach's alpha, split half methods, item discrimination, and
      item difficulty was investigated. On the other hand, various models of item
      response theory (IRT) and their statistics were compared in the group of latent
      class methods. RESULTS: Reliability statistics had values above 0.87. Item no. 7
      was found easy, item no. 45 difficult and item no. 64 fairly difficult according
      to the evaluations done by classical and item response theories. In terms of item
      discrimination, item no. 45 had lower, item no. 7 had middle and item no. 64 had
      high discrimination levels. The distribution graph shows that personal abilities
      are good enough to tick the correct choice. CONCLUSION: In this study, similar
      results were obtained by classical and latent methods. IRT can be considered
      perfect at a mathematical level, and if its assumptions are satisfied, it can
      easily perform assessments and measurements for most types of complex problems.
      Classical theory is easy to understand and to apply, while IRT is, on the
      contrary, sometimes rather difficult to understand and to implement.

PMID- 25772925
TI  - Dynamic assessment of Capparis spinosa buds on survival of periodontal ligament
      cells using a real-time cell analysis method.
AB  - BACKGROUND: Tooth avulsion is the most severe type of traumatic dental injuries
      and it results in the complete displacement of the tooth out of its socket in
      alveolar bone. Reimplantation of the tooth is considered to be a best treatment
      modality due to its biological and psychological advantages. Its prognosis
      depends on the extra alveolar time, the storage medium, and the patient's general
      health. OBJECTIVE: The aim of this study was to evaluate the effect of Capparis
      spinosa (C. spinosa) in maintaining the viability of human periodontal ligament
      (PDL) cells using a real-time cell analysis method. MATERIALS AND METHODS:
      Periodontal ligament cells were obtained from healthy human third molars
      extracted for orthodontic purposes. The storage media tested were: Dulbecco's
      Modified Eagle Medium (DMEM), C. spinosa, Hank's Balanced Salt Solution (HBSS),
      and light milk. A real-time cell analyzer system was used to evaluate cell
      viability. After seeding cell suspensions into the wells of the E-plate 96, PDL
      cells were treated with each of tested media and monitored for every 5 min for 26
      h. Statistical analysis of the data was accomplished using one-way analysis of
      variance complemented by the Tukey test. The level of significance was set at P <
      0.05. RESULTS: Dulbecco's Modified Eagle Medium (control) and C. spinosa groups
      had significantly higher cell index values compared with the HBSS and light milk
      (P < 0.05). Although, C. spinosa showed better results than DMEM (control), but
      this difference was not found statistically significant. CONCLUSION: Capparis
      spinosa can be a suitable, alternative storage medium for avulsed teeth.

PMID- 25772926
TI  - Effects of different cavity-disinfectants and potassium titanyl phosphate laser
      on microtensile bond strength to primary dentin.
AB  - AIM: The aim of this in vitro study was to compare the effects of different
      cavity-disinfectants and potassium titanyl phosphate (KTP) laser on microtensile
      bond strength to primary dentin. Chlorhexidine (CHX), propolis (PRO), ozonated
      water (OW), gaseous ozone (OG) and KTP laser were used for this purpose.
      METHODOLOGY: Twelve primary molar teeth were used in this study. One-third of the
      teeth (from coronal portion) were removed to obtain flat surfaces. After applying
      the cavity-disinfectants, an adhesive (prime and bond NT) was applied to dentin
      surfaces, and composite crowns were built up. One group received no pretreatment
      and was set as a control (CONT). Ten sticks were obtained from these samples and
      were stressed in tension until failure using a universal testing machine and the
      data were recorded. RESULTS: The mean strength values (in MPa) of the sticks were
      OW (11.12) > KTP (9.58) > CHX (7.58) > PRO (7.42) > CONT (6.38) > OG (5.84) and
      OW showed significantly higher results than the other groups, except KTP group (P
      < 0.05). CONCLUSIONS: OW and KTP might be used safely without compromising the
      bond strength of restorative materials.

PMID- 25772927
TI  - Shear bond strength of a self-etched resin cement to an indirect composite:
      effect of different surface treatments.
AB  - OBJECTIVES: The aim of this study was to compare the shear bond strength of resin
      cement (Rely X-U200) bonded to differently conditioned indirect composite
      samples. MATERIALS AND METHODS: Sixty-six composite resin specimens (5 mm in
      diameter and 3 mm in thickness) were prepared with an indirect composite resin
      (Grandia) and randomly divided into six groups. Surfaces of the samples were
      treated with one of the following treatments; %37 phosphoric acid etching,
      sandblasting, 1,5 W, 2 W and 3 W erbium, chromium: Yttrium-scandium-gallium
      garnet laser application. An untreated group was used as a control. In each group
      surface of the sample was analyzed with scanning electron microscopy. The
      remaining samples (n = 60) were built up with a self-adhesive resin cement (Rely
      X-U200) 3 mm in diameter and 2 mm height. After 24 h water storage at 37 degrees
      C, the prepared specimens were submitted to shear bond strength test. One-way
      analysis of variance was used to analyze the bond strength values of different
      groups. RESULTS: Highest shear bond strength values were observed in sandblasting
      group however there were not statistical difference among the tested surface
      treatment methods. CONCLUSION: In Shear bond strength of resin, cement was
      independent of the surface conditioning methods applied on tested indirect resin
      composite.

PMID- 25772928
TI  - "Evaluation of fracture strength of teeth restored with different types of posts
      luted with different luting cements": an in vitrostudy.
AB  - AIMS: The aim was to evaluate the incidence of root fracture of endodontically
      treated teeth reinforced with glass-fiber posts and metal posts luted with
      different luting cements. MATERIALS AND METHODS: Forty maxillary central incisors
      were sectioned at 1 mm of the cementoenamel junction and endodontically treated.
      The teeth were divided into four groups (n = 10) and restored with prefabricated
      metal posts and glass-fiber posts luted with resin-based luting cement and glass
      ionomer cement. Core built up was done using composite resin. The fracture
      strength was evaluated using an Instron universal testing machine (Model 4206,
      Instron Corp., Canton, MA). The results were recorded. STATISTICAL ANALYSIS USED:
      The Kruskal-Wallis test analysis test was used to analyze the data. RESULTS:
      Prefabricated metal post was statistically superior to the glass-fiber posts.
      Posts luted with resin-based luting cement were superior in fracture strength
      than glass ionomer cement. CONCLUSIONS: Teeth restored with prefabricated metal
      posts present higher fracture strength than those reinforced with glass-fiber
      posts. Posts luted with resin-based luting cement showed higher fracture strength
      than glass ionomer cement.

PMID- 25772929
TI  - Diagnosis of periodontal diseases using different classification algorithms: a
      preliminary study.
AB  - OBJECTIVE: The purpose of the proposed study was to develop an identification
      unit for classifying periodontal diseases using support vector machine (SVM),
      decision tree (DT), and artificial neural networks (ANNs). MATERIALS AND METHODS:
      A total of 150 patients was divided into two groups such as training (100) and
      testing (50). The codes created for risk factors, periodontal data, and
      radiographically bone loss were formed as a matrix structure and regarded as
      inputs for the classification unit. A total of six periodontal conditions was the
      outputs of the classification unit. The accuracy of the suggested methods was
      compared according to their resolution and working time. RESULTS: DT and SVM were
      best to classify the periodontal diseases with a high accuracy according to the
      clinical research based on 150 patients. The performances of SVM and DT were
      found 98% with total computational time of 19.91 and 7.00 s, respectively. ANN
      had the worst correlation between input and output variable, and its performance
      was calculated as 46%. CONCLUSIONS: SVM and DT appeared to be sufficiently
      complex to reflect all the factors associated with the periodontal status, simple
      enough to be understandable and practical as a decision-making aid for prediction
      of periodontal disease.

PMID- 25772930
TI  - Multimodal approach to blood conservation in the surgical patient.
AB  - Allogeneic blood remains a scarce and expensive resource, even as the risks of
      disease transmission and other complications associated with blood transfusion
      are well known. Blood conservation, however, is a quality-of-care concept that
      transcends these and other known and unknown complications of transfusion, to
      involve a gamut of strategies meant to prevent exposure of patients to allogeneic
      blood. In urging a halt to incessant allogeneic blood transfusion, we report
      three cases to highlight the benefits of multimodal multidisciplinary
      collaboration in blood conservation. The three patients were chosen on account of
      either religious objection to any blood transfusion or the likelihood of exposure
      to several units of allogeneic blood. The blood conservation plan proposed for
      each patient was discussed with the respective surgeon and patient. Multimodal
      multidisciplinary approach to blood conservation utilising combination of
      strategies best suited for each individual patient will remarkably reduce the
      exposure of patients to allogeneic blood thereby ensuring better use of the
      scarce resource, and and preventing potential clinical complications and
      spiritual trespass of Jehovah's Witnesses. 

PMID- 25772931
TI  - Dental exarticulation.
AB  - Tooth exarticulation or avulsion refers to the complete displacement of the tooth
      out of its socket. It is a complex injury, requiring immediate intervention for
      optimal results. Literature indicates that prolonged dry time and improper
      handling may be associated with increased risk of failure. Immediate replantation
      of the tooth allows for immediate restoration of esthetics and phonetics. This
      case report presents the management of an avulsed mature tooth in a young boy,
      with a two-year follow-up, which had been preserved in milk after around 15-20
      minutes of injury and transplanted after two hours at a dental hospital. Timely
      modified endodontic therapy prevented subsequent inflammatory root resorption. 

PMID- 25772932
TI  - Single-shot lamina technique of paravertebral block as an adjunct to general
      anesthesia for modified radical mastectomy.
AB  - Thoracic paravertebral block can be employed as an alternative or an adjunct to
      general anesthesia (GA) for breast cancer surgery. There is no report of this new
      lamina technique for catheter placement in our environment. In low-resource
      settings, potent opioids are lacking and the extended postoperative analgesia it
      provides makes this regional block an invaluable addition to an anesthetist's
      armamentarium. We describe this single-shot, but titratable technique used as an
      adjunct to GA for modified radical mastectomy with axillary dissection for breast
      cancer. The total intraoperative opioid analgesic 50 mg pethidine was received at
      induction. The patient's vital signs remained stable throughout surgery that
      lasted 115 min. Pain score charted every 10 min in the postanesthesia care unit
      using the verbal rating scale was 0. The time to the first request for rescue
      analgesic was 18 h after surgery for which paracetamol 1 g was adequate. 

PMID- 25772933
TI  - Progressive myelopathy, a consequence of intra-thecal chemotherapy: case report
      and review of the literature.
AB  - Intra-thecal chemotherapy is a recognized therapy for hematological malignancies
      such as acute lymphoblastic leukemia (ALL). Despite the advantage of these drugs
      in treating or preventing central nervous system disease, they are not without
      complications. The authors describe a 12-year-old girl with ALL, who developed
      progressive myelopathy following intra-thecal administration of cytosine
      arabinoside. Initial presentation was urine and fecal retention that progressed
      to paraplegia, and finally encephalopathy. magnetic resonance imaging of the
      neuroaxis showed T2-weighted foci of increased signal intensity within the
      substance of the cervical cord indicative of myelopathy. Physicians should be
      wary of this rare complication of intra-thecal chemotherapy. 

PMID- 25772934
TI  - Mutations in NDUFB11, encoding a complex I component of the mitochondrial
      respiratory chain, cause microphthalmia with linear skin defects syndrome.
AB  - Microphthalmia with linear skin defects (MLS) syndrome is an X-linked male-lethal
      disorder also known as MIDAS (microphthalmia, dermal aplasia, and sclerocornea).
      Additional clinical features include neurological and cardiac abnormalities. MLS
      syndrome is genetically heterogeneous given that heterozygous mutations in HCCS
      or COX7B have been identified in MLS-affected females. Both genes encode proteins
      involved in the structure and function of complexes III and IV, which form the
      terminal segment of the mitochondrial respiratory chain (MRC). However, not all
      individuals with MLS syndrome carry a mutation in either HCCS or COX7B. The
      majority of MLS-affected females have severe skewing of X chromosome
      inactivation, suggesting that mutations in HCCS, COX7B, and other as-yet
      unidentified X-linked gene(s) cause selective loss of cells in which the mutated
      X chromosome is active. By applying whole-exome sequencing and filtering for X
      chromosomal variants, we identified a de novo nonsense mutation in NDUFB11
      (Xp11.23) in one female individual and a heterozygous 1-bp deletion in a second
      individual, her asymptomatic mother, and an affected aborted fetus of the
      subject's mother. NDUFB11 encodes one of 30 poorly characterized supernumerary
      subunits of NADH:ubiquinone oxidoreductase, known as complex I (cI), the first
      and largest enzyme of the MRC. By shRNA-mediated NDUFB11 knockdown in HeLa cells,
      we demonstrate that NDUFB11 is essential for cI assembly and activity as well as
      cell growth and survival. These results demonstrate that X-linked genetic defects
      leading to the complete inactivation of complex I, III, or IV underlie MLS
      syndrome. Our data reveal an unexpected role of cI dysfunction in a developmental
      phenotype, further underscoring the existence of a group of mitochondrial
      diseases associated with neurocutaneous manifestations. 

PMID- 25772935
TI  - Meta-analysis of 65,734 individuals identifies TSPAN15 and SLC44A2 as two
      susceptibility loci for venous thromboembolism.
AB  - Venous thromboembolism (VTE), the third leading cause of cardiovascular
      mortality, is a complex thrombotic disorder with environmental and genetic
      determinants. Although several genetic variants have been found associated with
      VTE, they explain a minor proportion of VTE risk in cases. We undertook a meta
      analysis of genome-wide association studies (GWASs) to identify additional VTE
      susceptibility genes. Twelve GWASs totaling 7,507 VTE case subjects and 52,632
      control subjects formed our discovery stage where 6,751,884 SNPs were tested for
      association with VTE. Nine loci reached the genome-wide significance level of 5 *
      10(-8) including six already known to associate with VTE (ABO, F2, F5, F11, FGG,
      and PROCR) and three unsuspected loci. SNPs mapping to these latter were selected
      for replication in three independent case-control studies totaling 3,009 VTE
      affected individuals and 2,586 control subjects. This strategy led to the
      identification and replication of two VTE-associated loci, TSPAN15 and SLC44A2,
      with lead risk alleles associated with odds ratio for disease of 1.31 (p = 1.67 *
      10(-16)) and 1.21 (p = 2.75 * 10(-15)), respectively. The lead SNP at the TSPAN15
      locus is the intronic rs78707713 and the lead SLC44A2 SNP is the non-synonymous
      rs2288904 previously shown to associate with transfusion-related acute lung
      injury. We further showed that these two variants did not associate with known
      hemostatic plasma markers. TSPAN15 and SLC44A2 do not belong to conventional
      pathways for thrombosis and have not been associated to other cardiovascular
      diseases nor related quantitative biomarkers. Our findings uncovered unexpected
      actors of VTE etiology and pave the way for novel mechanistic concepts of VTE
      pathophysiology. 

PMID- 25772936
TI  - Mutations in the endothelin receptor type A cause mandibulofacial dysostosis with
      alopecia.
AB  - The endothelin receptor type A (EDNRA) signaling pathway is essential for the
      establishment of mandibular identity during development of the first pharyngeal
      arch. We report four unrelated individuals with the syndrome mandibulofacial
      dysostosis with alopecia (MFDA) who have de novo missense variants in EDNRA.
      Three of the four individuals have the same substitution, p.Tyr129Phe. Tyr129 is
      known to determine the selective affinity of EDNRA for endothelin 1 (EDN1), its
      major physiological ligand, and the p.Tyr129Phe variant increases the affinity of
      the receptor for EDN3, its non-preferred ligand, by two orders of magnitude. The
      fourth individual has a somatic mosaic substitution, p.Glu303Lys, and was
      previously described as having Johnson-McMillin syndrome. The zygomatic arch of
      individuals with MFDA resembles that of mice in which EDNRA is ectopically
      activated in the maxillary prominence, resulting in a maxillary to mandibular
      transformation, suggesting that the p.Tyr129Phe variant causes an EDNRA gain of
      function in the developing upper jaw. Our in vitro and in vivo assays suggested
      complex, context-dependent effects of the EDNRA variants on downstream signaling.
      Our findings highlight the importance of finely tuned regulation of EDNRA
      signaling during human craniofacial development and suggest that modification of
      endothelin receptor-ligand specificity was a key step in the evolution of
      vertebrate jaws. 

PMID- 25772939
TI  - Distress in relation to attenuated psychotic symptoms in the ultra-high-risk
      population is not associated with increased risk of psychotic disorder.
AB  - AIM: The 'ultra-high-risk' criteria identify a clinical population at
      substantially increased risk for progressing to schizophrenia and other psychotic
      disorders. Although a number of clinical variables predictive of transition to
      psychotic disorder have been identified within this population, the predictive
      value of the level of distress associated with attenuated psychotic symptoms has
      not yet been examined. This was the aim of the present study. METHOD: The level
      of distress (0-100) associated with attenuated psychotic symptoms was recorded
      for 70 ultra-high-risk (UHR) patients using the Comprehensive Assessment of At
      Risk Mental State (CAARMS). Transition to psychosis was assessed over a 16-month
      follow-up period. RESULTS: Of the 70 UHR patients, 15 transitioned to psychosis
      (21.4%). Of the four CAARMS subscales measuring attenuated positive symptoms,
      Perceptual Abnormalities was rated as the most distressing. There were no
      differences in CAARMS scales rated as the most distressing between those who
      transitioned to psychosis and those who did not. There was also no association
      between higher levels of distress associated with attenuated psychotic symptoms
      and transition to psychosis. CONCLUSION: Although the findings require
      replication, they indicate that the degree of distress associated with attenuated
      psychotic symptoms should not be used as a criterion for enriching UHR samples
      for risk of frank psychotic disorder.

PMID- 25772937
TI  - Submicroscopic deletions at 13q32.1 cause congenital microcoria.
AB  - Congenital microcoria (MCOR) is a rare autosomal-dominant disorder characterized
      by inability of the iris to dilate owing to absence of dilator pupillae muscle.
      So far, a dozen MCOR-affected families have been reported worldwide. By using
      whole-genome oligonucleotide array CGH, we have identified deletions at 13q32.1
      segregating with MCOR in six families originating from France, Japan, and Mexico.
      Breakpoint sequence analyses showed nonrecurrent deletions in 5/6 families. The
      deletions varied from 35 kbp to 80 kbp in size, but invariably encompassed or
      interrupted only two genes: TGDS encoding the TDP-glucose 4,6-dehydratase and
      GPR180 encoding the G protein-coupled receptor 180, also known as intimal
      thickness-related receptor (ITR). Unlike TGDS which has no known function in
      muscle cells, GPR180 is involved in the regulation of smooth muscle cell growth.
      The identification of a null GPR180 mutation segregating over two generations
      with iridocorneal angle dysgenesis, which can be regarded as a MCOR
      endophenotype, is consistent with the view that deletions of this gene, with or
      without the loss of elements regulating the expression of neighboring genes, are
      the cause of MCOR. 

PMID- 25772938
TI  - MicroRNA-155 regulates interferon-gamma production in natural killer cells via
      Tim-3 signalling in chronic hepatitis C virus infection.
AB  - Host immune responses must be tightly regulated by an intricate balance between
      positive and negative signals while fighting pathogens; persistent pathogens may
      usurp these regulatory mechanisms to dampen host immunity to facilitate survival
      in vivo. Here we report that Tim-3, a negative signalling molecule expressed on
      monocytes and T cells, is up-regulated on natural killer (NK) cells in
      individuals chronically infected with hepatitis C virus (HCV). Additionally, the
      transcription factor T-bet was also found to be up-regulated and associated with
      Tim-3 expression in NK cells during chronic HCV infection. MicroRNA-155 (miR
      155), an miRNA that inhibits signalling proteins involved in immune responses,
      was down-regulated in NK cells by HCV infection. This Tim-3/T-bet over-expression
      and miR-155 inhibition were recapitulated in vitro by incubating primary NK cells
      or NK92 cell line with Huh-7 hepatocytes expressing HCV. Reconstitution of miR
      155 in NK cells from HCV-infected patients led to a decrease in T-bet/Tim-3
      expression and an increase in interferon-gamma production. Blocking Tim-3
      signalling also enhanced interferon-gamma production in NK cells by improving
      signal transducer and activator of transcription-5 phosphorylation. These data
      indicate that HCV-induced, miR-155-regulated Tim-3 expression regulates NK cell
      function, suggesting a novel mechanism for balancing immune clearance and immune
      injury during chronic viral infection. 

PMID- 25772940
TI  - Validating Screening Tool in Malayalam for Mental Disorders.
AB  - OBJECTIVES: Valid screening tools are needed to identify Indian children and
      adolescents with mental health problems, both for clinical or research purposes.
      The present study validated the Strengths and Difficulties Questionnaire (SDQ) in
      Malayalam across different informants and sub-scales. METHODS: A sample of 150
      children and adolescents seen in a psychiatric clinic for children in Kerala,
      India was compared to a community sample of 1984 children from six surrounding
      urban and rural districts. Children in clinic and community samples were screened
      with the parent-report SDQ; those over 11 y completed the self-report SDQ. The
      community sample was also screened with the teacher-report SDQ and the clinical
      sample received formal diagnoses from a child psychiatrist blind to SDQ scores.
      The discriminative validity of the SDQ was investigated using Receiver Operator
      Characteristic (ROC) curves and by assessing Area Under the Curve (AUC). RESULTS:
      The SDQ discriminated reliably between clinical and community samples for the SDQ
      total score and its subscales. Within the clinic sample, 49 % of patients
      qualified for more than one broad diagnostic grouping. The SDQ discriminated
      between diagnostic categories in the clinic sample, but did so most effectively
      for conduct disorders. Based on the cut-offs that generated the highest combined
      value of sensitivity and specificity, the estimated rate of psychiatric disorder
      in the community sample was 13.6 % (parent-report) and 7.3 % (self-report).
      CONCLUSIONS: The SDQ is a useful screening tool for child and adolescent mental
      disorders for Malayalam speakers in Kerala, India.

PMID- 25772941
TI  - Dyskeratosis Congenita with Acute Pre B Cell Lymphoblastic Leukemia in a 10-year
      old Girl.

PMID- 25772942
TI  - Williams Syndrome with Infantile Spasms.

PMID- 25772943
TI  - Addisonian Crisis Due to Antitubercular Therapy.

PMID- 25772944
TI  - Iodide-free ionic liquid with dual redox couples for dye-sensitized solar cells
      with high open-circuit voltage.
AB  - A novel ionic-liquid mediator, 1-butyl-3-{2-oxo-2-[(2,2,6,6-tetramethylpiperidin
      4-yl)amino]ethyl}-1H-imidazol-3-ium selenocyanate (ITSeCN), has been successfully
      synthesized for dye-sensitized solar cells (DSSCs). ITSeCN possesses dual redox
      channels, imidazolium-functionalized 2,2,6,6-tetramethylpiperidine N-oxyl (TEMPO)
      and selenocyanate, which can serve as the cationic redox mediator and the anionic
      redox mediator, respectively. Therefore, ITSeCN has a favorable redox nature,
      which results in a more positive standard potential, larger diffusivity, and
      better kinetic heterogeneous rate constant than those of iodide. The DSSC with
      the ITSeCN electrolyte shows an efficiency of 8.38 % with a high open-current
      voltage (VOC ) of 854.3 mV, and this VOC value is about 150 mV higher than that
      for the iodide-based DSSC. Moreover, different electrocatalytic materials were
      employed to trigger the redox reaction of ITSeCN. The ITSeCN-based DSSC with the
      CoSe counter electrode achieved the best performance of 9.01 %, which suggested
      that transition-metal compound-type materials would be suitable for our newly
      synthesized ITSeCN mediator. 

PMID- 25772945
TI  - Homogeneous magnetic resonance imaging of brain abnormalities in bipolar spectrum
      disorders comorbid with Wilson's disease.
AB  - BACKGROUND: The purpose was to determine if brain damage in Wilson's disease (WD)
      is different in comorbid bipolar spectrum disorders (BDs), comorbid major
      depressive disorder (MDD) or without any mood disorders. METHODS: An
      observational study was conducted on consecutive patients from a center for WD
      care. The study sample was divided by psychiatric assessment into WD without any
      mood disorders, WD with BDs and WD with MDD negative at Mood Disorder
      Questionnaire (MDQ). RESULTS: Thirty-eight WD patients were recruited (53.2%
      females): 21 without mood disorders (55.2%), 9 with comorbid BDs (26.7%) and 8
      with MDD without MDQ+ (21.1%). The BDs showed a higher frequency of brain damage,
      reaching statistically significant differences in the basal ganglia (P<.001), in
      the overall brain (P<.003) and at the limit in the white matter (P<.05).
      CONCLUSIONS: In WD, comorbidity with BDs is associated with earlier evidence of
      brain damage, especially in the basal ganglia. The results confirm the importance
      of screening and early diagnosis of BDs in WD. Future follow-up studies on large
      samples are required to confirm if detection of BDs may be an early marker of
      brain damage and if a good therapeutic response in BDs may improve the prognosis
      of WD.

PMID- 25772946
TI  - New insights into the neurobiological mechanisms of major depressive disorders.
AB  - OBJECTIVE: To review the current evidence about the neurobiological mechanisms in
      major depressive disorders (MDD) and the key findings from studies using
      neuroimaging tools and animal models. METHOD: This paper gives an overview of the
      role of genetic and environmental factors in the pathophysiology of MDD and
      describes the structural changes in brain structures of depressed individuals. A
      closer look is given at the molecular processes and neurotransmitters implicated
      in this mental disorder. Moreover, this paper discusses key findings from recent
      research using animal models and their relevance for clinical applications.
      RESULTS: Although the exact cause of MDD is not known, there is enough evidence
      showing that genetic, psychological and environmental factors significantly
      increase the risk of developing this disease. Individuals affected by MDD exhibit
      a reduced volume of structures such as the amygdala, hippocampus and basal
      ganglia, as well as altered level of neurotransmitters in the brain. CONCLUSION:
      The studies presented in this review show promising results that could shed light
      on the molecular mechanisms of MDD. However, more work needs to be done to better
      understand this psychiatric disorder and promote the development of new treatment
      strategies.

PMID- 25772947
TI  - Organic anxiety in a woman with breast cancer receiving denosumab.
AB  - Hypocalcemia can induce heterogeneous psychiatric manifestations, and its
      etiology can be multifactorial. Herein, we describe a patient who had previously
      undergone resection of parathyroid glands, who presented with extreme anxiety and
      hypocalcemia after denosumab treatment for cancer-related bone metastasis. The
      anxiety subsided soon after correction of her serum calcium level. When denosumab
      is prescribed for patients with predisposing factors of hypocalcemia, such as
      hypoparathyroidism, clinicians should be aware of symptomatic hypocalcemia. 

PMID- 25772949
TI  - Facile assembly of oppositely charged silver sulfide nanoparticles into
      photoluminescent mesoporous nanospheres.
AB  - Inorganic mesoporous materials have been attracting increasing attention during
      the past decade. In the present work, photoluminescent Ag2S nanospheres with
      mesoporous structures were prepared by assembling Ag2S nanoparticles with
      opposite charges in aqueous phase. Without structure-directing templates,
      mesoporous Ag2S with well-ordered face-centered cubic superlattice structures and
      high specific surface area was obtained. The mesoporous Ag2S nanospheres had the
      same crystal phase as their precursors Ag2S nanoparticles. Different from their
      near-infrared emitting precursors, the mesoporous Ag2S nanospheres exhibited cyan
      emission under ultraviolet excitation. The large number of sulfur-related defects
      existing in the mesostructures is most likely responsible for the
      photoluminescence. This work provides new insights into fabricating
      photoluminescent mesostructured materials via scale-up strategy. 

PMID- 25772948
TI  - Pathogenic CD8+ T cells in experimental cerebral malaria.
AB  - Cerebral malaria (CM) is one the major complications occurring during malaria
      infection. The mechanisms leading to this syndrome are still not completely
      understood. Although it is clear that parasite sequestration is the key
      initiation factor, the downstream pathological processes are still highly
      debated. The experimental cerebral malaria (ECM) model, in which susceptible mice
      are infected with Plasmodium berghei ANKA, has led to the identification of
      CD8(+) T cells as the major mediator of ECM death. In this review, we discuss the
      recent advances and future developments in the understanding of the role of
      CD8(+) T cells in CM. 

PMID- 25772951
TI  - Approach to chronic wound infections.
AB  - Infection is the likeliest single cause of delayed healing in healing of chronic
      open wounds by secondary intention. If neglected it can progress from
      contamination to colonization and local infection through to systemic infection,
      sepsis and multiple organ dysfunction syndrome, and it can be life-threatening.
      Infection in chronic wounds is not as easy to define as in acute wounds, and is
      complicated by the presence of biofilms. There is, as yet, no diagnostic for
      biofilm presence, but it contributes to excessive inflammation - through
      excessive and prolonged stimulation of nitric oxide, inflammatory cytokines and
      free radicals - and activation of immune complexes and complement, leading to a
      delay in healing. Control of biofilm is a key part of chronic wound management.
      Maintenance debridement and use of topical antimicrobials (antiseptics) are more
      effective than antibiotics, which should be reserved for treating spreading local
      and systemic infection. The continuing rise of antimicrobial resistance to
      antibiotics should lead us to reserve their use for these indications, as no new
      effective antibiotics are in the research pipeline. Antiseptics are effective
      through many mechanisms of action, unlike antibiotics, which makes the
      development of resistance to them unlikely. There is little evidence to support
      the theoretical risk that antiseptics select resistant pathogens. However, the
      use of antiseptic dressings for preventing and managing biofilm and infection
      progression needs further research involving well-designed, randomized controlled
      trials. 

PMID- 25772950
TI  - A multicentre, prospective, randomised, blinded clinical trial to compare some
      perioperative effects of buprenorphine or butorphanol premedication before equine
      elective general anaesthesia and surgery.
AB  - REASONS FOR PERFORMING STUDY: Buprenorphine, a MU-agonist opioid, has recently
      been licensed for equine use, but butorphanol, a kappa-agonist opioid, is more
      commonly used in horses. The effect of the 2 opioids has not previously been
      compared in a large clinical study. OBJECTIVES: To compare post operative
      analgesia and physiological variables in horses undergoing elective surgery
      following premedication with either buprenorphine or butorphanol in a
      conventional clinical setting. STUDY DESIGN: Multicentre, prospective,
      randomised, blinded clinical investigation. METHODS: Eighty-nine healthy horses
      admitted for elective surgery to one of 6 UK equine veterinary clinics were
      premedicated with acepromazine, a nonsteroidal anti-inflammatory drug, and
      romifidine followed by intravenous (i.v.) buprenorphine or butorphanol.
      Anaesthesia was induced with diazepam/ketamine and maintained with isoflurane in
      oxygen. A range of surgical procedures were performed and supplementary
      anaesthetic agents given as required. Physiological variables were monitored
      during anaesthesia and pain, ataxia, sedation and vital function were assessed
      post operatively. Data were analysed using t-tests, ANOVA, Mann-Whitney U-test
      and Chi-squared test as appropriate and P<0.05 was regarded as significant,
      except for multiple comparisons, when P<0.01 was used. RESULTS: Surgery was
      carried out successfully in all cases and no mortality or serious morbidity
      occurred. Physiological variables remained within normal limits and all horses
      recovered successfully, most standing within 1 h of ceasing anaesthesia. There
      were no significant differences between groups in any variable except post
      operative pain when scores (simple descriptive scale) between 3 and 6 h were
      significantly lower after buprenorphine than after butorphanol. CONCLUSIONS:
      Horses experienced less post operative pain after buprenorphine than after
      butorphanol premedication. Compared with butorphanol, buprenorphine did not cause
      any different effects on vital function.

PMID- 25772952
TI  - Naegleria fowleri in Pakistan - an emerging catastrophe.

PMID- 25772953
TI  - Topical application of tranexamic acid reduces postoperative bleeding in open
      heart surgery: myth or fact?
AB  - OBJECTIVE: To determine the efficacy of topical application of Tranexamic acid in
      controlling postoperative bleeding in open-heart surgery. STUDY DESIGN: Double
      blind randomized control trial. PLACE AND DURATION OF STUDY: Departments of
      Cardiac Surgery and Intensive Care of Armed Forces Institute of Cardiology and
      National Institute of Heart Diseases (AFIC-NIHD), Rawalpindi, Pakistan, from May
      to October 2011. METHODOLOGY: A total of 100 consecutive adult patients
      fulfilling the inclusion criteria undergoing elective on-pump cardiac surgeries
      were randomly divided in groups 'A' and 'B'. A study solution that contained 2.5
      g of Tranexamic acid in 250 ml normal saline in group-A and equal amount of
      normal saline (placebo) in group-B was poured in the pericardial cavity over the
      mediastinal tissues before sternal closure. Postoperative bleeding was measured
      in both groups for 24 hours in the cardiac surgical ICU. Efficacy of Topical
      Tranexamic Acid / Placebo was measured in terms of mean postoperative bleeding in
      ml. Kindly again include these lines which seem to have been omitted in the final
      proof. RESULTS: There was significant difference in the mean postoperative
      bleeding within 24 hours among the two groups 340.1 +/- 112.4 ml in Tranexamic
      acid group vs. 665 +/- 187.28 ml in placebo group (p < 0.001). CONCLUSION:
      Patients who did not have topical Tranexamic acid before chest closure had a
      significantly higher postoperative bleeding. Topical Tranexamic acid application
      is an effective and economical way for controlling non-surgical bleeding in
      patients undergoing cardiac surgery with cardiopulmonary bypass.

PMID- 25772954
TI  - Mobile phone intervention to improve diabetes care in rural areas of Pakistan: a
      randomized controlled trial.
AB  - OBJECTIVE: To determine the effect of mobile phone intervention on HbA1c in type
      2 Diabetes Mellitus (DM) patients living in rural areas of Pakistan. STUDY
      DESIGN: Randomized controlled trial. PLACE AND DURATION OF STUDY: Department of
      Endocrinology, Liaquat National Hospital, Karachi, from December 2013 to June
      2014. METHODOLOGY: A total of 440 patients in intervention and control groups
      were enrolled. All patients between 18 - 70 years of age, residing in rural areas
      of Pakistan, HbA1c 3 8.0% and having personal functional mobile phone were
      included. The intervention group patients were called directly on mobile phone
      after every 15 days for a period of 4 months. They were asked about the self
      monitoring blood glucose, intake of medications, physical activity, healthy
      eating and were physically examined after 4 months. However, the control group
      was examined initially and after 4 months physically in the clinic and there were
      no mobile phone contacts with these patients. RESULTS: Patients in intervention
      group showed improvement (p < 0.001) in following diet plan from 17.3% at
      baseline to 43.6% at endline, however, the control group showed insignificant
      increase (p=0.522) from 13.6% at baseline to 15.9% at endline. Intervention group
      (RR = 2.71, 95% CI = 1.18 - 6.40) showed significant positive association with
      normalization of HbA1c levels. The relationship was adjusted for age, gender,
      socio-economic status, ethnicity, education, hypertension, medication, BMI, diet,
      LDL levels and physical activity. Dietary restriction and low LDL levels also
      showed significant associations with reduced HbA1c levels on multivariate
      analysis. CONCLUSION: Mobile phone technology in rural areas of Pakistan was
      helpful in lowering HbA1c levels in intervention group through direct
      communication with the diabetic patients. Lowering LDL and following diabetic
      diet plan can reduce HbA1c in these patients and help in preventing future
      complications.

PMID- 25772955
TI  - Use of box simulators for improving intraoperative laparoscopic skills - an
      essential tool for the surgeon in training.
AB  - OBJECTIVE: To compare the improvement of intraoperative laparoscopic skills by
      measuring GOALS score between residents who have undergone simulator training
      with those who have not received any simulator training. STUDY DESIGN: A
      randomized controlled trial. PLACE AND DURATION OF STUDY: Department of Surgery,
      Services Hospital, Lahore, from August 2013 to February 2014. METHODOLOGY: Thirty
      residents belonging to year 1, 2 and 3 were included in the study. They were
      randomly divided into 2 groups. Both groups had a baseline evaluation with GOALS
      score while performing dissection of gallbladder from liver bed during
      laparoscopic cholecystectomy. Group-A underwent formal training on simulators
      whereas group-B did not receive any formal training on simulators. After 6
      months, a repeat evaluation was done again by measuring GOALS score while
      performing gallbladder dissection. RESULTS: Baseline GOALS scores of both the
      groups were similar. Group-A baseline score was 7.66 +/- 0.93 and group-B score
      was 7.46 +/- 1.04 (p = 0.585). However repeat scores for group-A showed a
      significant improvement (an increase of 7.16 +/- 1.48 to 14.76 +/- 1.67, p <
      0.001) from baseline scores. Residents in group-B improved their scores by 2.30
      +/- 0.99 to 9.76 +/- 0.79 (p < 0.001). When inter group comparison was done the
      second score of group-A was significantly higher than that of group-B (14.76 +/-
      1.67 vs. 9.76 +/- 0.79, p < 0.001). Inter-rater reliability was moderately
      significant (Kappa 0.540).

PMID- 25772956
TI  - Prognostic value of Gc-globulin in Chinese patients with acute-on-chronic
      hepatitis B liver failure.
AB  - OBJECTIVE: To determine dynamic Gc-globulin level change in Acute-on-Chronic
      Hepatitis B Liver Failure (ACHBLF) patients, and evaluate the prognostic value of
      Gc-globulin. STUDY DESIGN: An analytical study. PLACE AND DURATION OF STUDY: The
      First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou,
      China, from January 2010 to December 2012. METHODOLOGY: A total of 54 consecutive
      Chinese ACHBLF patients and 30 healthy volunteers as controls were recruited from
      2010 to 2012. The patients were divided into improved group and aggravated group.
      Gc-globulin levels were determined in both groups and mean values compared with
      significance at p < 0.05. Cut-off value was also determined. RESULTS: The Gc
      globulin level was significantly decreased in ACHBLF patients (p < 0.001). Gc
      globulin levels were significantly higher in improved patients than in aggravated
      patients, and a 215 mg/L cut-off value carried the best prognostic information.
      On longitudinal observations, Gc-globulin gradually elevated in improved groups.
      However, in aggravated groups, the Gc-globulin levels were always below normal
      levels and no significant change was observed before or after the treatment (p >
      0.05). CONCLUSION: Gc-globulin monitoring offers a rapid and accurate method to
      estimate treatment outcomes on admission and an effective temporal indicator of
      curative effects in ACHBLF patients at an optimal cut-off value of 215 mg/L.

PMID- 25772957
TI  - Comparison of articaine and lignocaine for uncomplicated maxillary exodontia.
AB  - OBJECTIVE: To compare single buccal articaine injection versus conventional
      lignocaine buccal and palatal injections for uncomplicated maxillary tooth
      extractions. STUDY DESIGN: Single blinded randomized control trial. PLACE AND
      DURATION OF STUDY: The outpatient department of Oral and Maxillofacial Surgery,
      Armed Forces Institute of Dentistry, Rawalpindi, from February to September 2011.
      METHODOLOGY: Patients aged 20 - 60 years under simple extraction in the maxillary
      arch were included in the study. Patients were randomly divided into two groups-A
      and B toss method. Maxillary teeth were divided into three groups; group-1
      (posterior teeth) including first, second and third molars on either side, group
      2 (middle teeth) including the premolars and group-3 (anterior teeth) including
      incisors and canines. Group-A (study group) received buccal infiltration of 4%
      articaine with 1:200,000 adrenaline and group-B (control group) received buccal
      and palatal infiltration of 2% lignocaine/HCl with 1:100,000 adrenaline. Faces
      Pain Scale (FPS) and a Visual Analogue Score (VAS) was used for objective and
      subjective assessment of per operative pain respectively. RESULTS: A total of 194
      patients were included in the study. Group-A comprised of 100 patients while
      group-B consisted of 94 patients. The mean age of the total sample was 41.12 +/-
      13.6 years. Statistically significant difference was found for the VAS scores of
      anteriors (p=0.9), premolars (p=0.2) and molars (p=0.2) for groups A and B. The
      FPS scores for both groups were also statistically insignificant (p=0.864).
      CONCLUSION: Buccal infiltration with a single articaine injection and lignocaine
      buccal and palatal infiltration were equally effective for maxillary exodontia.

PMID- 25772958
TI  - Correlation of MCQ and SEQ scores in written undergraduate ophthalmology
      assessment.
AB  - OBJECTIVE: To determine the psychometric worth of Multiple-Choice Questions
      (MCQs) and Short-Essay Questions (SEQs) used in internal summative assessment of
      undergraduate ophthalmology annual send-up examination and to ascertain the
      quality of items using subjective measures. STUDY DESIGN: Correlational
      analytical study. PLACE AND DURATION OF STUDY: Fatima Jinnah Medical College,
      Lahore, from January to March 2012. METHODOLOGY: Fourth year MBBS students
      appearing in their written send-up annual examination in ophthalmology. The MCQ
      and SEQ scores were correlated for validity and reliability. Construct validity
      was estimated (Pearson correlation coefficient). MCQ's split-half reliability
      (Spearman correlation coefficient) and SEQ's inter-rater reliability (Pearson
      correlation coefficient) were also estimated. RESULTS: Moderate correlation was
      seen between MCQ and SEQ scores (r=0.5, p < 0.01). Split-half reliability of MCQs
      had moderate correlation (r=0.4, p < 0.01) while inter-rater reliability of SEQs
      scores showed high correlation (r=0.9, p < 0.01). Most of the MCQs (55%) and
      SEQ's (90%) were at recall level of Bloom's taxonomy. MCQs (30%) attained a
      higher level (interpretation) as compared to SEQ's (10%). None of the MCQ and SEQ
      attained problem solving level. CONCLUSION: Using variety of tools for assessment
      improves both the validity and reliability enabling examiners to draw fair
      conclusions about a student's ability. Validity and reliability can be further
      improved by arranging training opportunities for item writers to achieve accurate
      transfer of hypothetical construct in the form of an item. This is crucial since
      essential and important learning outcomes can only be assessed with valid and
      reliable tools.

PMID- 25772959
TI  - Mortality trend among hemodialysis patients during the islamic month of Ramadan:
      a 24 years retrospective study.
AB  - OBJECTIVE: The effect of month of Ramadan on the mortality in hemodialysis
      patients, and to compare it with that in all other Islamic months. STUDY DESIGN:
      A descriptive study. PLACE AND DURATION OF STUDY: Hemodialysis Unit, The Kidney
      Center, Karachi, from January 1989 to December 2012. METHODOLOGY: All those
      patients who were diagnosed to have end stage kidney disease and on maintenance
      hemodialysis for more than 3 months, regardless of underlying cause of kidney
      failure were included. Patients with acute kidney injury were excluded. Status of
      the patients was recorded at the end of the study period. The fasting status of
      the patients was not mentioned. The deaths of the patients were further evaluated
      and frequencies of death in all twelve Islamic months were calculated. RESULTS: A
      total of 1,841 patients were registered, out of whom 897 (48.7%) died, and 269
      (14.6%) survived till the end of the study. One thousand and fifty six (57.3%)
      were males, 651 (35.4%) were diabetic. Total number of 143 (7.76%) events
      occurred in Ramadan, out of which 94 patients died which make nearly 11% of the
      total deaths distributed in 12 Islamic months. Frequency of death was higher in
      Ramadan when compared with other months. CONCLUSION: Ramadan reflected a higher
      frequency of death. Therefore, there is a need to evaluate the risk factors in a
      prospective study so that the dialysis patients can be better managed during this
      period.

PMID- 25772960
TI  - Parenteral iron therapy in the treatment of iron deficiency anemia during
      pregnancy: a randomized controlled trial.
AB  - OBJECTIVE: To compare the efficacy and safety profile of total dose infusion of
      low molecular weight iron dextran with divided doses of intravenous iron sucrose
      for the treatment of iron deficiency anemia during pregnancy. STUDY DESIGN:
      Randomized controlled trial. PLACE AND DURATION OF STUDY: Shifa International
      Hospital, Islamabad, over a period of two years from January 2008 to December
      2009. METHODOLOGY: Pregnant women at gestational age more than 12 weeks with the
      confirmed diagnosis of Iron Deficiency Anemia (IDA) were divided into two groups.
      In the group-A, intravenous iron sucrose was given in divided doses while in the
      group-B, total daily intake of Low Molecular Weight (LMW) of iron dextran was
      given. Post-infusion Hemoglobin (Hb) was checked at 4 weeks and at the time of
      delivery for both groups. Paired sample t-test is applied and comparison (in
      terms of rise in hemoglobin from pre to post) of both groups was not found to be
      significant. RESULTS: In the group-A (iron sucrose group), mean pre-infusion Hb
      levels was 9.09 +/- 0.83 gm/dl. Mean increase in Hemoglobin (Hb) was 10.75 +/-
      1.097 gm/dl after 4 weeks of infusion and 11.06 +/- 0.866 gm/dl at delivery (p <
      0.001). In group-B (iron dextran group) pre-infusion haemoglobin was 8.735 +/-
      0.956 gm/dl and the mean increase in hemoglobin was 10.613 +/- 1.22 gm/dl at 4
      week while mean increase of 10.859 +/- 1.11 gm/dl at the time of delivery (p <
      0.001). CONCLUSION: Both LMW iron dextran, as well as iron sucrose are equally
      effective in treatment of IDA during pregnancy, however, LMW iron dextran has the
      advantage of single visit treatment.

PMID- 25772961
TI  - Differential expression of p63 in hydropic and molar gestations.
AB  - OBJECTIVE: To observe the differential expression of p63 in hydropic and molar
      gestation. STUDY DESIGN: Cross-sectional analytical study. PLACE AND DURATION OF
      STUDY: Department of Pathology, Basic Medical Sciences Institute, Jinnah
      Postgraduate and Medical Centre, Karachi, from January 2006 to June 2013.
      METHODOLOGY: Ninety placental biopsies including 30 cases each of hydropic
      abortions, partial hydatidiform mole and complete hydatidiform mole were analyzed
      for morphological features and results of immunohistochemical staining. Results
      were described as frequency. Significance was determined using test of
      proportions with significance at p < 0.05. RESULTS: Out of 30 cases of hydropic
      abortion, 6 were negative, 15 were weak, 4 were moderate and 5 showed strong
      degree of intensity for p63. Out of 30 cases of partial hydatidiform mole, 3 were
      negative, 2 showed weak, 4 showed moderate and 21 cases showed strong degree of
      intensity for p63. All 30 cases of complete hydatidiform mole strongly stained
      for p63. CONCLUSION: The intensity of staining of p63 was stronger in cases of
      molar pregnancy as compared to hydropic abortion. There was loss of p63
      expression in cytotrophoblastic cells in all abortions. In limited resources
      settings, where facilities for PCR/FISH and DNA ploidy analysis is not available,
      the authors advocate p63 in routine clinical practice to provide the most refined
      diagnosis of hydatidiform moles.

PMID- 25772962
TI  - Duration of nasal packs in the management of epistaxis.
AB  - OBJECTIVE: To compare the efficacy of nasal packs for 12 and 24 hours in the
      management of epistaxis. STUDY DESIGN: Quasi experimental study. PLACE AND
      DURATION OF STUDY: Combined Military Hospital, Nowshera and Heavy Industries
      Taxilla Hospital, from October 2012 to April 2013. METHODOLOGY: A total of 60
      patients presenting with epistaxis were selected and were divided into two groups
      of 30 patients each. Patients in both the groups were managed by nasal packs. In
      group-A packs were removed after 12 hours while in group-B after 24 hours.
      Symptoms of headache, lacrimation and recurrence of bleeding were recorded. SPSS
      20 was used for data analysis and p-value less than 0.01 was considered
      significant. RESULTS: There was significant difference for headache between
      removal of nasal packs after 12 hours and 24 hours (p < 0.001). There was
      significant difference for excessive lacrimation at 12 and 24 hours (p = 0.001).
      No significant difference was observed for recurrence of bleed when nasal packs
      were removed at 12 and 24 hours (p = 0.317). CONCLUSION: Duration in removal of
      nasal packs after 12 or 24 hours made a difference in the management of
      epistaxis. Symptoms of headache and excessive lacrimation were significantly
      higher when nasal packs were removed after 24 hours. It is recommended that
      patient could be managed with lesser duration of packs after episode of epistaxis
      to avoid inconvenience.

PMID- 25772963
TI  - Are BP readings taken after a patient-physician encounter in a real-world clinic
      scenario the lowest of all the readings in a clinic visit.
AB  - OBJECTIVE: To determine the difference in Blood Pressure (BP) readings taken
      before, during and after the clinic encounter. STUDY DESIGN: Descriptive study.
      PLACE AND DURATION OF STUDY: Cardiology Clinic, The Aga Khan University Hospital,
      Karachi, from January to August 2013. METHODOLOGY: Hypertensive and normotensive
      participants aged 3 18 years were recruited. Pre-clinic BP was measured by a
      nurse and in-clinic BP by a physician. After 15 minutes, two post-clinic BP
      readings were taken at 1 minute interval. All readings were taken using Omron
      HEM7221-E. RESULTS: Out of 180 participants, males were 57% and 130 (71%) were
      hypertensive. Mean SBP (Systolic BP) taken preclinic, in-clinic, post-clinic 1
      and post-clinic 2 were: 126 +/- 20 mmHg, 131 +/- 23 mmHg, 126 +/- 20 mmHg and 121
      +/- 21 mmHg respectively (p < 0.001). Mean DBP (Diastolic BP) taken pre-clinic,
      in-clinic, post-clinic 1 and post-clinic 2 were 77 +/- 12 mmHg, 81 +/- 13 mmHg,
      79 +/- 12 mmHg and 79 +/- 11 mmHg respectively (p < 0.001). CONCLUSION: BP taken
      in the post-clinic setting may significantly be the lowest reading in a clinic
      encounter, making in-clinic BP unreliable to diagnose or manage hypertension.

PMID- 25772964
TI  - Evolution of DNA sequencing.
AB  - Sanger and coworkers introduced DNA sequencing in 1970s for the first time. It
      principally relied on termination of growing nucleotide chain when a
      dideoxythymidine triphosphate (ddTTP) was inserted in it. Detection of terminated
      sequences was done radiographically on Polyacrylamide Gel Electrophoresis (PAGE).
      Improvements that have evolved over time in original Sanger sequencing include
      replacement of radiography with fluorescence, use of separate fluorescent markers
      for each nucleotide, use of capillary electrophoresis instead of polyacrylamide
      gel electrophoresis and then introduction of capillary array electrophoresis.
      However, this technique suffered from few inherent limitations like decreased
      sensitivity for low level mutant alleles, complexities in analyzing highly
      polymorphic regions like Major Histocompatibility Complex (MHC) and high DNA
      concentrations required. Several Next Generation Sequencing (NGS) technologies
      have been introduced by Roche, Illumina and other commercial manufacturers that
      tend to overcome Sanger sequencing limitations and have been reviewed.
      Introduction of NGS in clinical research and medical diagnostics is expected to
      change entire diagnostic approach. These include study of cancer variants,
      detection of minimal residual disease, exome sequencing, detection of Single
      Nucleotide Polymorphisms (SNPs) and their disease association, epigenetic
      regulation of gene expression and sequencing of microorganisms genome. 

PMID- 25772965
TI  - Endometrial stromal sarcoma: a rare entity.
AB  - Endometrial Stromal Sarcoma (ESS) is a hormone sensitive tumor. It is a rare
      gynecological tumor and is considered to occur more often in pre-menopausal
      women. A proper pre-operative diagnosis is difficult and confirmed in most cases
      after hysterectomy for a presumed benign disease. Endometrial sampling,
      ultrasound, and magnetic resonance imaging can provide diagnostic clues. For
      early disease complete surgical cure is possible, however, adjuvant therapy is
      available for recurrence. This case of Low Grade Endometrial Stromal Sarcoma
      (LGESS) in a 21 years old woman was presented as irregular vaginal bleeding.
      Clinical diagnosis of fibroid was made but analysis of endometrium showed ESS
      confirmed on hysterectomy specimen. One should consider it in any case with rapid
      fibroid enlargement. 

PMID- 25772966
TI  - Herpes zoster involving penis and scrotum: an unusual occurrence.
AB  - Herpes zoster is an infectious vesicular skin rash in a dermatomal distribution
      caused by Varicella zoster virus. It occurs very uncommonly in sacral dermatomes.
      We describe a case with rash on penis and scrotum due to involvement of S2
      dermatome in a young male. The disease followed an uneventful course and the
      patient recovered completely without any sequelae or complications. This case is
      being presented to highlight its unusual location and to discuss differentiation
      from another viral infection commonly seen at this site. 

PMID- 25772967
TI  - Ophthalmic manifestations of linear nevus sebaceous/organoid nevus syndrome.
AB  - Linear Nevus Sebaceous Syndrome (LNSS) is a rare sporadic oculoneurocutaneous
      disorder, also classified as Organoid Nevus Syndrome. It consists of a triad of
      midline facial linear nevus sebaceous, central nervous system and ocular
      abnormalities. To the best of authors' knowledge ophthalmic features of LNSS have
      never been reported in Pakistani population. We report two cases of LNSS,
      associated with multiple cutaneous nevus sebaceous lesions, complex ocular
      choristomas and rare bilateral presentation in one patient. Ocular choristomas
      included limbal dermoids, dermolipomas at superior fornices and chroidal
      choristoma. Ocular surface was successfully reconstructed by excision of limbal
      dermoids, partial keratectomy and amniotic membrane transplant. 

PMID- 25772968
TI  - Depression among hospitalized and non-hospitalized gonadal cancer patients in
      tertiary care public hospitals in Karachi.
AB  - The study aimed at determining the differences in the levels of depression
      between hospitalized and non-hospitalized Gonadal cancer patients in tertiary
      care public hospitals in Karachi. The present study was conducted at the Jinnah
      Postgraduate Medical Centre and Civil Hospital, Karachi, from July to October
      2009. One hundred adult patients diagnosed with Gonadal cancer volunteered for
      the study. Cases with any other co-morbidity were excluded. Urdu version of
      Siddiqui Shah Depression Scale (SSDS) was administered. Purposive and snowball
      sampling methods were used for data collection. The ages of participants in the
      sample ranged from 20 to 27 years with the mean age of 23.85 years. The
      participants belonged to the lower and middle classes. Out of the 30 hospitalized
      gonadal cancer patients 40% were moderately depressed and 60% were severely
      depressed, whereas out of 70 non-hospitalized gonadal cancer patients 74.3% were
      mildly depressed, 24.3% were moderately depressed and only 1.4% were severely
      depressed, which clearly indicated that the depression level of hospitalized
      gonadal cancer patients was high as compared to non-hospitalized gonadal cancer
      patients. 

PMID- 25772969
TI  - Thyroid storm associated with multinodular goiter: a difficult problem to treat.

PMID- 25772970
TI  - Gastric Antral Vascular Ectasia (GAVE): an overlooked diagnosis.

PMID- 25772971
TI  - Prospects of e-Health in federally administered tribal areas of Pakistan.

PMID- 25772972
TI  - Half-squat or jump squat training under optimum power load conditions to
      counteract power and speed decrements in Brazilian elite soccer players during
      the preseason.
AB  - The purpose of this study was to test which specific type of exercise (i.e., jump
      squat (JS) or half-squat (HS)) is more effective at maintaining speed and power
      abilities throughout a preseason in soccer players. Twenty-three male soccer
      players were randomly allocated into two groups: JS and HS. The mean propulsive
      power, vertical jumping ability, and sprinting performance were evaluated before
      and after 4 weeks of a preseason period. The optimum power loads for the JS and
      HS exercises were assessed and were used as load-references. The soccer players
      performed 10 power oriented training sessions in total. Both JS and HS maintained
      power in JS and speed abilities (P > 0.05, for main effects and interaction
      effect) as indicated by ANCOVA. Both groups demonstrated reduced power during HS
      (ES = -0.76 vs. -0.78, for JS and HS, respectively); both groups improved
      acceleration (ACC) from 5 to 10 m (ES = 0.52). JS was more effective at reducing
      the ACC decrements over 0-5 m (ES = -0.38 vs. -0.58, for JS and HS,
      respectively). The HS group increased squat jump height (ES = 0.76 vs. 0.11, for
      HS and JS, respectively). In summary, JS is more effective in reducing the ACC
      capacity over very short sprints while HS is more effective in improving squat
      jump performance. Both strategies improve ACC over longer distances. New training
      strategies should be implemented/developed to avoid concurrent training effects
      between power and endurance adaptations during professional soccer preseasons. 

PMID- 25772974
TI  - Efficacy of a web-based, center-based or combined physical activity intervention
      among older adults.
AB  - With more social support and environment-centered interventions being recommended
      in web-based interventions, this study examined the efficacy of three
      intervention conditions aimed at promoting physical activity (PA) in older
      adults. The efficacy analyses included the self-reported PA level, stage of
      change for PA and awareness about PA among participants. Eligible participants (N
      = 149; M = 65 years old, SD = 6), recruited in a unique Belgian French-speaking
      municipality, were randomized in four research arms for a 3-month intervention:
      (i) web-based; (ii) center-based; (iii) mixed (combination of web- and center
      based); and (iv) control (no intervention). Web-based condition included a PA
      website and monthly tailored emails whereas center-based condition comprised 12
      sessions (1 per week) of group exercising. With a significant increase in PA, the
      PA stage of change and the PA awareness at 12 months, the mixed intervention
      condition seemed to include the key social and motivating elements for
      sustainable behavior change. Center-based intervention was more likely to produce
      significant improvements of the PA level and the stage of change for PA change
      whereas web-based intervention was more likely to extend the awareness about PA. 

PMID- 25772973
TI  - M. leprae components induce nerve damage by complement activation: identification
      of lipoarabinomannan as the dominant complement activator.
AB  - Peripheral nerve damage is the hallmark of leprosy pathology but its etiology is
      unclear. We previously identified the membrane attack complex (MAC) of the
      complement system as a key determinant of post-traumatic nerve damage and
      demonstrated that its inhibition is neuroprotective. Here, we determined the
      contribution of the MAC to nerve damage caused by Mycobacterium leprae and its
      components in mouse. Furthermore, we studied the association between MAC and the
      key M. leprae component lipoarabinomannan (LAM) in nerve biopsies of leprosy
      patients. Intraneural injections of M. leprae sonicate induced MAC deposition and
      pathological changes in the mouse nerve, whereas MAC inhibition preserved myelin
      and axons. Complement activation occurred mainly via the lectin pathway and the
      principal activator was LAM. In leprosy nerves, the extent of LAM and MAC
      immunoreactivity was robust and significantly higher in multibacillary compared
      to paucibacillary donors (p = 0.01 and p = 0.001, respectively), with a highly
      significant association between LAM and MAC in the diseased samples (r = 0.9601,
      p = 0.0001). Further, MAC co-localized with LAM on axons, pointing to a role for
      this M. leprae antigen in complement activation and nerve damage in leprosy. Our
      findings demonstrate that MAC contributes to nerve damage in a model of M. leprae
      induced nerve injury and its inhibition is neuroprotective. In addition, our data
      identified LAM as the key pathogen associated molecule that activates complement
      and causes nerve damage. Taken together our data imply an important role of
      complement in nerve damage in leprosy and may inform the development of novel
      therapeutics for patients.

PMID- 25772975
TI  - Anti-leukemic activities of alcoholic extracts of two traditional Indian
      medicinal plants.
AB  - The present work aimed to investigate the anticancer in vitro activity of two
      plants commonly used in traditional Indian medicine: Zingiber officinale Roscoe
      and Nerium oleander L. The extracts of these plants were tested in vitro on
      several human leukemic cell lines, K562, THP-1, MOLT-4 and Jurkat. Cell growth
      inhibition was observed for both plant extracts with 50% inhibitory concentration
      (IC50) values ranging between 1 and 28 MUg/mL using SRB (sulphorodamine B) and
      MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide] assays.
      Enhanced cell growth inhibition was observed when the extracts were combined with
      imatinib. Exposed cells showed cell cycle arrest, DNA damage and cytochrome c
      release, indicating that the mechanism of cytotoxicity could be via mitochondrial
      mediated apoptotic pathways. Combination of the extracts of these plants with
      standard cancer treatment may be a way of enhancing responses. Clinical studies
      in patients with chronic myeloid leukemia are planned at our center. 

PMID- 25772976
TI  - Usefulness of white-light imaging-guided narrow-band imaging for the differential
      diagnosis of small ampullary lesions.
AB  - BACKGROUND: Small ampullary tumors and inflammatory lesions have similar
      endoscopic findings and are difficult to differentiate. Narrow-band imaging (NBI)
      can visualize microvessels and mucosal microstructure clearly and is widely used
      to diagnose early gastric and colon cancer. OBJECTIVE: To evaluate the usefulness
      of NBI for differentiating ampullary tumors from benign diseases. DESIGN:
      Retrospective cohort study. SETTING: Tertiary-care hospital. PATIENTS: All 45
      patients who had suspicious ampullary lesions (enlarged or protruded morphology)
      during duodenoscopy and underwent NBI between March 2010 and January 2011.
      INTERVENTIONS: NBI. MAIN OUTCOME MEASUREMENTS: NBI images were assessed for
      irregular villous arrangement, irregular villous size, ridge disappearance,
      demarcation with normal villi, and abnormal microvasculature. Histology of NBI
      guided lesion biopsy specimens provided the final diagnoses. Agreement between
      NBI images and histologic findings was analyzed. RESULTS: Of the 60 ampullary
      lesions, 11, 26, and 23 were adenocarcinomas, adenomas, and benign inflammatory
      diseases, respectively. Irregular villous arrangement, irregular villous size,
      ridge disappearance, demarcation with normal villi, and abnormal microvasculature
      were observed in 45%, 63%, 50%, 48%, and 58% of the lesions, respectively.
      Multivariate analysis revealed that irregular villous arrangement (odds ratio
      [OR] 15.76; 95% confidence interval [CI], 3.38-64.12; P < .001) and abnormal
      microvasculature (OR 86.63; 95% CI, 14.56-515.41; P < .001) were significant
      independent factors for identifying ampullary adenomas and adenocarcinoma. All
      tumors had at least one abnormal NBI feature. LIMITATIONS: Retrospective design.
      CONCLUSION: The NBI findings of irregular villous arrangement and/or abnormal
      microvasculature were useful for differentially diagnosing ampullary tumors. NBI
      may complement the accurate diagnosis of ampullary lesions by white-light
      imaging.

PMID- 25772977
TI  - On the dual phosphorescence of xanthone and chromone in glassy hydrocarbon hosts.
AB  - Trace quantities of hydrogen-bonding impurities in otherwise highly purified and
      dried glassy hydrocarbon matrices at 77 K can modify the relative triplet state
      energy levels, and hence the photophysical properties of two aromatic ketones,
      xanthone and chromone, to the extent that the intrinsic spectroscopic properties
      are obscured. The intrinsic spectroscopic properties of each are revealed in
      multicrystalline n-alkane Shpol'skii matrices, and also can be observed in
      rigorously purified and dried hydrocarbon glasses at 77 K. The extreme
      sensitivity to stoichiometric, and even substoichiometric quantities of hydrogen
      bonding impurities arises from the near-degeneracy of the two lowest-lying
      triplet states, and the sensitive nature of the n->pi* blueshift phenomena to
      specific hydrogen-bonding interactions. 

PMID- 25772978
TI  - The blockade of dihydropyridine channels prevents an increase in MU-calpain level
      under m. soleus unloading.

PMID- 25772979
TI  - Identification of genetic determinants of influenza A virus resistance to
      adamantanes and neuraminidase inhibitors using biological microarray.

PMID- 25772980
TI  - About the mechanism of membrane permeability enhancement by substances in their
      intermolecular complexes with polysaccharide arabinogalactan from larches Larix
      sibirica and Larix gmelinii.

PMID- 25772981
TI  - Synthesis of a new fluorescent analogue of proglyprol and study of the mechanisms
      of its transport into the cultured rat pheochromocytoma cells.

PMID- 25772982
TI  - Mechanism of the cytotoxic action of immunophototoxin 4D5scFV-miniSOG on HER2/neu
      positive cancer cells.

PMID- 25772983
TI  - Analysis of dependence of antidepressant properties of TrkB receptor ligands on
      MAP-kinase pathway activation.

PMID- 25772984
TI  - Immunization with non-toxic variants of Shiga toxin type 2 (Stx2) generates high
      titers of protective antibodies.

PMID- 25772985
TI  - Nucleotide excision repair factor XPC-RAD23B is poly(ADP-ribosylated) by the
      poly(ADP-ribose) polymerase 1.

PMID- 25772986
TI  - Effect of ionizing radiation on the luminescence of mycelium of luminous fungus
      Neonothopanus nambi.

PMID- 25772987
TI  - Biosorption of (241)Am from aqueous solutions and its biochemical fractionation
      in Pleurotus ostreatus mycelium.

PMID- 25772988
TI  - Lipid status of larvae and adults of the White Sea herring Clupea pallasii
      marisalbi Berg (Clupeiformes, Clupeidae).

PMID- 25772989
TI  - Effect of dimeric netropsin analogue 15Lys-bis-Nt and acyclovir on the
      reproduction of herpes simplex virus type 1. The search for variants of herpes
      virus with drug resistance to 15Lys-bis-Nt and acyclovir.

PMID- 25772990
TI  - The action of the peptide drug Semax on the currents of AMPA receptors of rat
      cerebellar Purkinje cells.

PMID- 25772991
TI  - Cooperative synthesis of dopamine in the striatum of normal and parkinsonial
      mice.

PMID- 25772992
TI  - Venoms of kraits Bungarus multicinctus and Bungarus fasciatus contain
      anticoagulant proteins.

PMID- 25772993
TI  - Interchromosomal gene conversion as a regular mechanism of loss of heterozygosity
      (LOH) in early zygote of Drosophila melanogaster.

PMID- 25772994
TI  - Nitric oxide regulates the chemoattractant activity of defensin HNP-1 in the
      blood.

PMID- 25772996
TI  - An economic analysis of adherence engineering to improve use of best practices
      during central line maintenance procedures.
AB  - OBJECTIVE: Adherence engineering applies human factors principles to examine non
      adherence within a specific task and to guide the development of materials or
      equipment to increase protocol adherence and reduce human error. Central line
      maintenance (CLM) for intensive care unit (ICU) patients is a task through which
      error or non-adherence to protocols can cause central line-associated bloodstream
      infections (CLABSIs). We conducted an economic analysis of an adherence
      engineering CLM kit designed to improve the CLM task and reduce the risk of
      CLABSI. METHODS: We constructed a Markov model to compare the cost-effectiveness
      of the CLM kit, which contains each of the 27 items necessary for performing the
      CLM procedure, compared with the standard care procedure for CLM, in which each
      item for dressing maintenance is gathered separately. We estimated the model
      using the cost of CLABSI overall ($45,685) as well as the excess LOS (6.9 excess
      ICU days, 3.5 excess general ward days). RESULTS: Assuming the CLM kit reduces
      the risk of CLABSI by 100% and 50%, this strategy was less costly (cost savings
      between $306 and $860) and more effective (between 0.05 and 0.13 more quality
      adjusted life-years) compared with not using the pre-packaged kit. We identified
      threshold values for the effectiveness of the kit in reducing CLABSI for which
      the kit strategy was no longer less costly. CONCLUSION: An adherence engineering
      based intervention to streamline the CLM process can improve patient outcomes and
      lower costs. Patient safety can be improved by adopting new approaches that are
      based on human factors principles.

PMID- 25772995
TI  - Alpha-ketoglutarate dehydrogenase complex-dependent succinylation of proteins in
      neurons and neuronal cell lines.
AB  - Reversible post-translation modifications of proteins are common in all cells and
      appear to regulate many processes. Nevertheless, the enzyme(s) responsible for
      the alterations and the significance of the modification are largely unknown.
      Succinylation of proteins occurs and causes large changes in the structure of
      proteins; however, the source of the succinyl groups, the targets, and the
      consequences of these modifications on other proteins remain unknown. These
      studies focused on succinylation of mitochondrial proteins. The results
      demonstrate that the alpha-ketoglutarate dehydrogenase complex (KGDHC) can serve
      as a trans-succinylase that mediates succinylation in an alpha-ketoglutarate
      dependent manner. Inhibition of KGDHC reduced succinylation of both cytosolic and
      mitochondrial proteins in cultured neurons and in a neuronal cell line. Purified
      KGDHC can succinylate multiple proteins including other enzymes of the
      tricarboxylic acid cycle leading to modification of their activity. Inhibition of
      KGDHC also modifies acetylation by modifying the pyruvate dehydrogenase complex.
      The much greater effectiveness of KGDHC than succinyl-CoA suggests that the
      catalysis owing to the E2k succinyltransferase is important. Succinylation
      appears to be a major signaling system and it can be mediated by KGDHC.
      Reversible post-translation modifications of proteins are common and may regulate
      many processes. Succinylation of proteins occurs and causes large changes in the
      structure of proteins. However, the source of the succinyl groups, the targets,
      and the consequences of these modifications on other proteins remains unknown.
      The results demonstrate that the mitochondrial alpha-ketoglutarate dehydrogenase
      complex (KGDHC) can succinylate multiple mitochondrial proteins and alter their
      function. Succinylation appears to be a major signaling system and it can be
      mediated by KGDHC. 

PMID- 25772997
TI  - On-field management and return-to-play in sports-related concussion in children:
      Are children managed appropriately?
AB  - OBJECTIVES: On-field management and return-to-play guidelines aim to ensure the
      identification and appropriate management of the concussed athlete. Compliance
      with current guidelines in many settings is unknown. We assessed whether key
      components of current concussion guidelines are being followed in child athletes.
      DESIGN: Prospective observational study. METHODS: Data were collected from
      children (5-18 years) presenting to a paediatric emergency department with sport
      related concussion via researcher-administered surveys in the emergency
      department and during a follow up phone call. On hospital discharge all patients
      received a return to sports fact sheet based on the International Concussion in
      Sports Group. RESULTS: Ninety-three had sustained a concussion (mean age 12.7 (+/
      0.27) years, 83% male). Sports played included Australian Football (47%), soccer
      (12%), rugby (9%) basketball (8%), other (25%). 82% participated in organised
      sports. Concussive signs or symptoms included loss of consciousness (41%),
      disorientation (36%), vomiting (23%), amnesia (30%), headache (60%). For
      concussive injury in organised sports (n=76), overall 42% were not managed
      according to recommended guidelines: 19% were not immediately removed from play,
      29% were allowed to return to play on the same day and 27% were not assessed by
      qualified personnel. 93% of parents and 96% of patients were unaware of
      concussion or return-to-play guidelines from their organisations. Overall, 72%
      were compliant with provided return-to-play guidelines. CONCLUSIONS: Many
      children with sports related-concussion are not formally assessed on-field and
      continue to play. On-field concussion management and return to play practices are
      often suboptimal. Awareness and education of coaches, teachers, parents and
      children need to be improved.

PMID- 25772998
TI  - Migraine management in children.
AB  - Migraine management in children relies on understanding the difference between
      adult and childhood migraine, being able to identify childhood migraine variants
      and knowledge of both the pediatric and adult literature regarding treatment. 

PMID- 25772999
TI  - The clinical presentation of chronic traumatic encephalopathy.
AB  - Chronic traumatic encephalopathy (CTE) is a progressive neurodegenerative
      disorder attributed to repetitive mild traumatic brain injury. The diagnosis in a
      living individual can be challenging and can be made definitively only at
      autopsy. The symptoms are often nonspecific and overlap with neurodegenerative
      disorders such as Alzheimer's disease (AD) and frontotemporal dementia (FTD).
      Higher exposure to repetitive head trauma increases the risk of CTE. Genetic risk
      factors such as presence of an apolipoprotein E epsilon4 allele may be important.
      Individuals have varying degrees of cognitive, behavioral, and motor decline.
      Limitations in the manner in which data have been obtained over the years have
      led to different clinical descriptions of CTE. At present, there are no
      biomarkers to assist in the diagnosis. Standard neuroimaging may show nonspecific
      atrophic changes; however, newer imaging modalities such as positron emission
      tomography (PET) and diffusion tensor imaging (DTI) show promise.
      Neuropsychological testing may be helpful in determining the pattern of cognitive
      or behavioral decline. 

PMID- 25773000
TI  - Sleep disorders in multiple sclerosis. Review.
AB  - Sleep disorders are common in patients with multiple sclerosis (MS) and play a
      crucial role in health and quality of life; however, they are often overlooked.
      The most important sleep disorders in this context are as follows: insomnia,
      restless legs syndrome, periodic limb movement disorders, and sleep-related
      breathing disorders (SRBD). It is unclear if MS-related processes (lesions, brain
      atrophy) can cause symptomatic forms of sleep apnea. MS-related narcolepsy-like
      symptoms are described in the literature and, in some cases, have resolved with
      methylprednisolone pulse therapy. Similarly, REM sleep behavior disorder (RBD) is
      very rare in MS, but it can be an initial sign of MS where cortisone therapy may
      be helpful and can be taken into account in this specific context. Independent
      diagnosis and treatment is required for all of the abovementioned conditions.
      Treating physicians and neurologists should be aware of these comorbidities and
      initiate specific therapy. Highly fatigued or sleepy MS patients should have
      polysomnography in order not to overlook these diagnoses. 

PMID- 25773001
TI  - Clinical utility of ocular vestibular-evoked myogenic potentials (oVEMPs).
AB  - Over the last years, vestibular-evoked myogenic potentials (VEMPs) have been
      established as clinical tests of otolith function. Complementary to the cervical
      VEMPs, which assess mainly saccular function, ocular VEMPs (oVEMPs) test
      predominantly utricular otolith function. oVEMPs are elicited either with air
      conducted (AC) sound or bone-conducted (BC) skull vibration and are recorded from
      beneath the eyes during up-gaze. They assess the vestibulo-ocular reflex and are
      a crossed excitatory response originating from the inferior oblique eye muscle.
      Enlarged oVEMPs have proven to be sensitive for screening of superior canal
      dehiscence, while absent oVEMPs indicate a loss of superior vestibular nerve
      otolith function, often seen in vestibular neuritis (VN) or vestibular
      Schwannoma. 

PMID- 25773003
TI  - Comparison of regional gray matter volume abnormalities in Alzheimer's disease
      and late life depression with hippocampal atrophy using VSRAD analysis: a voxel
      based morphometry study.
AB  - Previous voxel-based morphometry (VBM) studies revealed that hippocampal volume
      loss in patients with late life depression (LLD) is associated with cognitive
      impairment and a higher risk for dementia. However, LLD patients can experience
      hippocampal atrophy without cognitive impairment. Thus, while LLD and AD can show
      comparable hippocampal atrophy, they may encompass different neuropathological
      changes. Using VBM, we therefore investigated differences in regional gray matter
      changes in 17 late-onset LLD patients and 21 AD patients (without a history of
      LLD) who exhibited comparably severe atrophy of the entorhinal cortex and the
      parahippocampal gyrus on MRI scans for voxel-based specific regional analysis
      system for AD (VSRAD). Relative to the VSRAD database for healthy individuals,
      significant atrophy was observed in mesial temporal lobe structures and the
      anterior cingulate cortex in both groups. Atrophy of the posterior cingulate
      cortex and precuneus was observed only in the AD group. Comparisons of gray
      matter volume by multivariate analysis of variance revealed significantly reduced
      volume of the right middle and inferior temporal gyrus, uncus, posterior
      cingulate cortex, and precuneus in the AD group only, suggesting impairment of
      different networks in AD and LLD. Indeed, structural changes in the posterior
      part of the default-mode network are believed to be associated with cognitive
      impairments specific to AD. 

PMID- 25773002
TI  - PBMC telomerase activity, but not leukocyte telomere length, correlates with
      hippocampal volume in major depression.
AB  - Accelerated cell aging, indexed in peripheral leukocytes by telomere shortness
      and in peripheral blood mononuclear cells (PBMCs) by telomerase activity, has
      been reported in several studies of major depressive disorder (MDD). However, the
      relevance of these peripheral measures for brain indices that are presumably more
      directly related to MDD pathophysiology is unknown. In this study, we explored
      the relationship between PBMC telomerase activity and leukocyte telomere length
      and magnetic resonance imaging-estimated hippocampal volume in un-medicated
      depressed individuals and healthy controls. We predicted that, to the extent
      peripheral and central telomerase activity are directly related, PBMC telomerase
      activity would be positively correlated with hippocampal volume, perhaps due to
      hippocampal telomerase-associated neurogenesis, neuroprotection or neurotrophic
      facilitation, and that this effect would be clearer in individuals with increased
      PBMC telomerase activity, as previously reported in un-medicated MDD. We did not
      have specific hypotheses regarding the relationship between leukocyte telomere
      length and hippocampal volume, due to conflicting reports in the published
      literature. We found, in 25 un-medicated MDD subjects, that PBMC telomerase
      activity was significantly positively correlated with hippocampal volume; this
      relationship was not observed in 18 healthy controls. Leukocyte telomere length
      was not significantly related to hippocampal volume in either group (19
      unmedicated MDD subjects and 17 healthy controls). Although the nature of the
      relationship between peripheral telomerase activity and telomere length and the
      hippocampus is unclear, these preliminary data are consistent with the
      possibility that PBMC telomerase activity indexes, and may provide a novel window
      into, hippocampal neuroprotection and/or neurogenesis in MDD. 

PMID- 25773004
TI  - Discussion of "On Bayesian Estimation of Marginal Structural Models".

PMID- 25773005
TI  - Drug safety in acute migraine treatment.
AB  - INTRODUCTION: A number of drugs are available for acute migraine treatment, but
      they are not all effective for all patients and all attacks. The safety profiles
      of migraine drugs limit their use in patients with certain comorbid conditions,
      and adverse effects may also reduce the level of patient compliance. AREAS
      COVERED: The different types of acute migraine drugs are discussed, with
      particular regard to safety issues and potential adverse effects. The frequent
      use of analgesics, ergot alkaloids and triptans may result in the development of
      medication overuse headache (MOH). EXPERT OPINION: The initiation of a migraine
      attack is not fully understood, and therefore treatment aimed at causative
      factors is currently not available. The tolerability and adverse effects of the
      drugs available at present often limit their use. NSAIDs are frequently
      associated with gastrointestinal, and possibly also cardiovascular side effects.
      Ergot alkaloids may induce arterial vasoconstriction, while the administration of
      triptans is contraindicated in cardiovascular, cerebrovascular and peripheral
      vascular diseases. The frequent use of these drugs poses the risk of the
      development of MOH. There is a need for pathomechanism-based drugs, and for the
      future achievement of personalized medicine.

PMID- 25773006
TI  - Genome-scale genetic screen of lead ion-sensitive gene deletion mutations in
      Saccharomyces cerevisiae.
AB  - Pb (lead) is one of the most widespread and toxic heavy metal contaminants and
      imposes potential harm to human health. Pb ions cause cellular damage and induce
      loss of cell viability. However, mechanisms regulating Pb toxicity remain poorly
      understood. Through a genome-scale screen, we have identified 30 yeast single
      gene deletion mutants that are sensitive to lead ions. These genes are involved
      in the metabolism, transcription, protein synthesis, cell cycle and DNA
      processing, protein folding, modification, destination, as well as cellular
      transport process. Comparative analyses to cadmium-sensitive mutations identified
      from previous studies indicate that overlapping genes of lead- and cadmium
      sensitive mutations are involved in both the metabolism and the cellular
      transport process. Furthermore, eleven lead-sensitive mutants show elevated
      levels of lead contents in response to lead stress. Our findings provide a basis
      to understand molecular mechanisms underlying the detoxification of lead ions by
      yeast cells. 

PMID- 25773007
TI  - The influence of ethnicity in the association of WC, WHR, hypertension and PGC
      1alpha (Gly482Ser), UCP2 -866 G/A and SIRT1 -1400 T/C polymorphisms with T2D in
      the population of Punjab.
AB  - AIM: To assess the effect of ethnicity, the association of WC, WHR and
      hypertension along with PGC-1alpha (Gly482Ser), UCP2 -866 G/A and SIRT1 -1400 T/C
      polymorphisms in seven endogamous caste groups and pooled population of Punjab.
      METHODS: Study was conducted on 1813 individuals (859 T2D patients and 954
      healthy controls) belonging to seven endogamous groups. Waist and hip
      circumference, height, weight and blood pressure were recorded following standard
      protocol using designed performa. PGC-1alpha (Gly482Ser) and UCP2 -866 G/A
      polymorphisms were genotyped using PCR RFLP and SIRT1 -1400 T/C was genotyped by
      direct DNA sequencing. RESULTS: WHR conferred risk in Brahmins (p=0.00003),
      Khtaris (p=0.001) and SCs (p=0.02). Similarly, we detected that WC conferred risk
      in BCs (p=0.012), Brahmins (p=0.016), Jat Sikhs (0.00025), Khatris (0.005) and
      SCs (p=0.015). In pooled population, all three factors imparted risk (WHR
      (p=0.00001), hypertension (p=0.003) and WC (p=0.0000016)). With respect to gene
      polymorphism, PGC-1alpha (Gly482Ser) was associated in Banias (p=0.0003), Jat
      Sikhs (p=0.003) and Khatris (p=0.03). Similarly, UCP2 -866 G>A showed risk in
      Banias (p=0.000004), BCs (p=0.01) and SCs (p=0.01). However, SIRT1 -1400 T>C
      showed risk only in Khatris (p=0.004). In the pooled population of Punjab, both
      PGC-1alpha (Gly482Ser) [p=0.001] and UCP2 -866 G>A (p=0.0001) polymorphisms
      provided risk. Interaction analysis showed 72% of the patients had risk
      combination of PGC-1alpha XA and UCP2-866 XA genotypes. CONCLUSIONS: Based on the
      data, Khatris were found to be showing the highest susceptibility to T2D followed
      by SCs. Different combinations of factors provided risk in each caste group and
      in pooled population. Therefore, to curve the menace of T2D, detailed information
      about the ethnic background of the individual will be very useful for proper
      medical intervention.

PMID- 25773008
TI  - Genes and life-style factors in BELFAST nonagenarians: Nature, Nurture and
      Narrative.
AB  - Understanding how to 'Age Longer and Age Well' is a priority for people
      personally, for populations globally and for government policy. Nonagenarians are
      the oldest members of our societies and survivors of their generation.
      Approximately 10 % of nonagenarians reach 90 years and beyond in good condition
      and seem to have a combination of both age-span and health-span. But what are the
      factors which help people reach their ninetieth birthday and beyond in good
      condition? Are they genetics, as in 'nature', or do they depend on 'nurture' and
      are related to environment, or are both factors inextricably intertwined within
      the concept of behavioural genetics? Nonagenarians have rich life experiences
      that can teach us much about ageing well; they are reservoirs of genetic, life
      style and behavioural information which can help dissect out how to live not only
      longer but better. Personal family history and narrative are powerful tools that
      help to determine familial traits, beliefs and social behaviours and when used in
      parallel with new biotechnology methods inform and elaborate causality. Here we
      present themes and insights from personal narrative enquiry from nonagenarian
      participants from the Belfast Elderly Longitudinal Free-living Ageing STudy
      (BELFAST) about factors they consider important for good quality ageing and
      relate these insights to the emerging genetics and life-style evidence associated
      with healthy longevity. 

PMID- 25773009
TI  - Biomarkers of oxidative stress and redox status in a short-term low-dosed
      multivitamin and mineral supplementation study in two human age groups.
AB  - A 60-day intervention study was conducted in which the participants took a low
      dose of a multivitamin and mineral supplement. The study consists of a final
      number of 66 volunteers (30 males and 36 females), divided into two age groups of
      30-35 and 60-65 years. For 30 days they took a multivitamin and mineral
      supplement with 1* the recommended daily intake (RDI) followed by another 30 days
      with 2* the RDI. The aim of the study was to monitor oxidative stress and redox
      status of both young and old age groups. In serum, the expected increase of the
      water-soluble vitamins folate and vitamin B12 was observed with a concomitant
      decrease in homocysteine. Serum biomarkers of oxidative stress, the reactive
      oxygen metabolites, of the antioxidant status, the biological antioxidant
      potential did not change. However, the total thiol levels in serum, biomarker of
      the redox status, decreased significant, only in both groups of elderly after 60
      days. In erythrocytes, there was a change in the glutathione metabolism as
      observed by an increase in glutathione reductase and to a lower extend in
      glutathione peroxidase, indicating an increase in oxidative stress in all groups.
      It is concluded that a low-dosed multivitamin and -mineral supplementation have
      different effects on the redox status in young versus old. It remained to explain
      why a low dose of a multivitamin and -mineral supplement cause increased
      oxidative stress. 

PMID- 25773010
TI  - Molecular margin of surgical resections--where do we go from here?

PMID- 25773011
TI  - Crossover among structural motifs in Pd-Au nanoalloys.
AB  - The crossovers among the most abundant structural motifs (icosahedra, decahedra
      and truncated octahedra) of Pd-Au nanoalloys have been determined theoretically
      in a size range between 2 and 7 nm and for three compositions equivalent to
      Pd3Au, PdAu and PdAu3. The chemical ordering and segregation optimisation are
      performed via Monte Carlo simulations using semi-empirical tight-binding
      potentials fitted to ab initio calculations. The chemical configurations are then
      quenched via molecular dynamic simulations in order to compare their energy and
      characterize the equilibrium structures as a function of the cluster size. For
      the smaller sizes (of around 300 atoms and fewer) the structures are also
      optimized at the electronic level within ab initio calculations in order to
      validate the semi-empirical potential. The predictions of the crossover sizes for
      the nanoalloys cannot be simply extrapolated from the crossover of the pure
      nanoparticles but imply stress release phenomena related to the size misfit
      between the two metals. Indeed, alloying extends the range of stability of the
      icosahedron beyond that of the pure systems and the energy differences between
      decahedra and truncated octahedra become asymptotic, around the sizes of 5-6 nm.
      Nevertheless, such equilibrium results should be modulated regarding kinetic
      considerations or possible gas adsorption under experimental conditions. 

PMID- 25773012
TI  - Dynamic modelling of radionuclide uptake by marine biota: application to the
      Fukushima nuclear power plant accident.
AB  - The dynamic model D-DAT was developed to study the dynamics of radionuclide
      uptake and turnover in biota and sediments in the immediate aftermath of the
      Fukushima accident. This dynamics is determined by the interplay between the
      residence time of radionuclides in seawater/sediments and the biological half
      lives of elimination by the biota. The model calculates time-variable activity
      concentration of (131)I, (134)Cs, (137)Cs and (90)Sr in seabed sediment, fish,
      crustaceans, molluscs and macroalgae from surrounding activity concentrations in
      seawater, with which to derive internal and external dose rates. A central
      element of the model is the inclusion of dynamic transfer of radionuclides
      to/from sediments by factorising the depletion of radionuclides adsorbed onto
      suspended particulates, molecular diffusion, pore water mixing and bioturbation,
      represented by a simple set of differential equations coupled with the biological
      uptake/turnover processes. In this way, the model is capable of reproducing
      activity concentration in sediment more realistically. The model was used to
      assess the radiological impact of the Fukushima accident on marine biota in the
      acute phase of the accident. Sediment and biota activity concentrations are
      within the wide range of actual monitoring data. Activity concentrations in
      marine biota are thus shown to be better calculated by a dynamic model than with
      the simpler equilibrium approach based on concentration factors, which tends to
      overestimate for the acute accident period. Modelled dose rates from external
      exposure from sediment are also significantly below equilibrium predictions. The
      model calculations confirm previous studies showing that radioactivity levels in
      marine biota have been generally below the levels necessary to cause a measurable
      effect on populations. The model was used in mass-balance mode to calculate total
      integrated releases of 103, 30 and 3 PBq for (131)I, (137)Cs and (90)Sr,
      reasonably in line with previous estimates. 

PMID- 25773013
TI  - Autologous skeletal-muscle-derived cell injection for anal incontinence due to
      obstetric trauma: a 5-year follow-up of an initial study of 10 patients.
AB  - AIM: Our aim was to determine whether the benefits of autologous skeletal-muscle
      derived cell injection to treat obstetric anal incontinence are sustained at 5
      years. METHOD: An observational study was performed of 10 women suffering from
      obstetric anal incontinence refractory to non-surgical therapy. Autologous
      skeletal-muscle-derived cells were injected into the external sphincter defect
      under ultrasound guidance. Incontinence diaries and quality of life
      questionnaires were obtained pre-implantation and annually after implantation for
      5 years. Anal physiology testing was performed before implantation and at 1, 2
      and 5 years after implantation. The end-points included were adverse events,
      Wexner incontinence scores, incontinence episodes, anal squeeze pressures and
      quality of life over 5 years. An independent statistician used multilevel linear
      regression to analyse changes in repeated measures over time. Any skewed
      distributions were log transformed prior to analysis. RESULTS: No procedure
      related adverse events occurred and haematological and biochemical parameters
      were normal during the 5-year period. There were sustained significant
      improvements in the Wexner incontinence score and reduced frequency of
      defaecation and number of incontinence episodes (all comparisons P < 0.001). Anal
      resting and squeeze pressures showed sustained improvement (all P < 0.001) and
      quality of life improved overall (P < 0.001), including all submeasures studied
      (P < 0.001). CONCLUSION: Autologous skeletal-muscle-derived cells to treat
      obstetric anal incontinence resulted in sustained improvement in incontinence
      episodes, physiological measurements of anal function and quality of life at 5
      years.

PMID- 25773014
TI  - Design, synthesis, and structure-activity relationships of 1-ethylpyrazole-3
      carboxamide compounds as novel hypoxia-inducible factor (HIF)-1 inhibitors.
AB  - Hypoxia-inducible factor (HIF)-1 is well known as a promising target for cancer
      chemotherapy. By screening an in-house chemical library using a hypoxia
      responsive luciferase reporter gene assay, we identified CLB-016 (1) containing 1
      ethylpyrazole-3-carboxamide as a HIF-1 inhibitor (IC50=19.1MUM). In a subsequent
      extensive structure-activity relationship (SAR) study, we developed compound 11Ae
      with an IC50 value of 8.1MUM against HIF-1-driven luciferase activity. Compounds
      1 and 11Ae were shown to significantly suppress the HIF-1-mediated hypoxia
      response, including carbonic anhydrase IX (CAIX) gene expression and migration of
      human sarcoma HT1080 cells. These results revealed 1-ethylpyrazole-3-carboxamide
      as a novel scaffold to develop promising anti-cancer drugs targeting the HIF-1
      signaling pathway.

PMID- 25773015
TI  - Sulfonamide inhibition studies of the gamma-carbonic anhydrase from the Antarctic
      cyanobacterium Nostoc commune.
AB  - A carbonic anhydrase (CA, EC 4.2.1.1) belonging to the gamma-class has been
      cloned, purified and characterized from the Antarctic cyanobacterium Nostoc
      commune. The enzyme showed a good catalytic activity for the physiologic reaction
      (hydration of carbon dioxide to bicarbonate and a proton) with the following
      kinetic parameters, kcat of 9.5*10(5)s(-1) and kcat/KM of 8.3*10(7)M(-1)s(-1),
      being the gamma-CA with the highest catalytic activity described so far. A range
      of aromatic/heterocyclic sulfonamides and one sulfamate were investigated as
      inhibitors of the new enzyme, denominated here NcoCA. The best NcoCA inhibitors
      were some sulfonylated sulfanilamide derivatives possessing elongated molecules,
      aminobenzolamide, acetazolamide, benzolamide, dorzolamide, brinzolamide and
      topiramate, which showed inhibition constants in the range of 40.3-92.3nM. As 1,5
      bisphosphate carboxylase/oxygenase (RubisCO) and gamma-CAs are closely associated
      in carboxysomes of cyanobacteria for enhancing the affinity of RubisCO for CO2
      and the efficiency of photosynthesis, investigation of this new enzyme and its
      affinity for modulators of its activity may bring new insights in these crucial
      processes.

PMID- 25773016
TI  - Design and synthesis of new potassium channel activators derived from the ring
      opening of diazoxide: study of their vasodilatory effect, stimulation of elastin
      synthesis and inhibitory effect on insulin release.
AB  - Benzenesulfonylureas and benzenesulfonylthioureas, as well as
      benzenecarbonylureas and benzenecarbonylthioureas, were prepared and evaluated as
      myorelaxants on 30mMKCl-precontracted rat aortic rings. The most active compounds
      were further examined as stimulators of elastin synthesis by vascular smooth
      muscle cells and as inhibitors of insulin release from pancreaticbeta-cells. The
      drugs were also characterized for their effects on glycaemia in rats.
      Benzenesulfonylureas and benzenesulfonylthioureas did not display any myorelaxant
      activity on precontracted rat aortic rings. Such an effect could be attributed to
      their ionization at physiological pH. By contrast, almost all
      benzenecarbonylureas and benzenecarbonylthioureas displayed a myorelaxant
      activity, in particular the benzenecarbonylureas with an oxybenzyl group linked
      to the ortho position of the phenyl ring. The vasodilatory activity of the most
      active compounds was reduced when measured in the presence of 80mMKCl or in the
      presence of 30mM KCl and 10MUM glibenclamide. Such results suggested the
      involvement, at least in part, of KATP channels. Preservation of a vasodilatory
      activity in rat aortic rings without endothelium indicated that the site of
      action of such molecules was located on the vascular smooth muscle cells and not
      on the endothelial cells. Some of the most active compounds also stimulated
      elastin synthesis by vascular smooth muscle cells. Lastly, most of the active
      vasorelaxant drugs, except 15k and 15t at high concentrations, did not exhibit
      marked inhibitory effects on the insulin releasing process and on glycaemia,
      suggesting a relative tissue selectivity of some of these compounds for the
      vascular smooth muscle.

PMID- 25773017
TI  - Role of cytotoxic therapy with hematopoietic cell transplantation in the
      treatment of Hodgkin lymphoma: guidelines from the American Society for Blood and
      Marrow Transplantation.
AB  - The role of hematopoietic cell transplantation (HCT) in the therapy of Hodgkin
      lymphoma (HL) in pediatric and adult patients is reviewed and critically
      evaluated in this systematic evidence-based review. Specific criteria were used
      for searching the published literature and for grading the quality and strength
      of the evidence and the strength of the treatment recommendations. Treatment
      recommendations based on the evidence are included and were reached unanimously
      by a panel of HL experts. Both autologous and allogeneic HCT offer a survival
      benefit in selected patients with advanced or relapsed HL and are currently part
      of standard clinical care. Relapse remains a significant cause of failure after
      both transplant approaches, and strategies to decrease the risk of relapse remain
      an important area of investigation. 

PMID- 25773018
TI  - Antihypertensive drugs, hypotension, and ischemic colitis.

PMID- 25773019
TI  - Children tell white lies to make others feel better.
AB  - We investigated whether children tell white lies simply out of politeness or as a
      means to improve another person's mood. A first experimental phase probed
      children's individual insight to use white lies when prosocial behaviour was
      called for. We compared a situation in which a person had expressed sadness about
      her artwork and the goal was to make her feel better (Sad condition) with a
      situation in which a person was indifferent about her work (Neutral condition).
      Children at 7 years and older were more likely to tell a white lie than the blunt
      truth in the Sad over the Neutral condition. Five-year-olds showed only a trend.
      A second phase tested whether children selectively use white lie telling after it
      was modelled by an adult. Results showed that after modelling, children from all
      age groups were significantly more likely to use white lies in the Sad condition
      than in the Neutral condition. Taken together, these results show that children
      are attentive to another person's affective states when choosing whether to tell
      a white lie or tell the truth. We discuss the emergence of this behaviour in
      relation to children's developing social cognition and the increasing
      sophistication of children's prosocial behaviour. 

PMID- 25773020
TI  - Differentiation of enantiomers by 2D NMR spectroscopy at 1 T using residual
      dipolar couplings.
AB  - Differentiating enantiomers using 2D bench-top NMR spectroscopy. Spectrometers
      working with permanent magnets at 1 T field strength allow the acquisition of 2D
      data sets. In conjunction with previously reported chiral alignment media, this
      setup allows the measurement of enantiomeric excess via residual dipolar
      couplings in stretched gelatine as a result of the reduced line width obtained by
      2D J-resolved spectroscopy. 

PMID- 25773044
TI  - Electric and magnetic hotspots in dielectric nanowire dimers.
AB  - We study the formation of the electric and magnetic near-field hotspots in
      dielectric cylindrical dimers. We compare dielectric and metallic dimers by using
      experimental data for all materials and consider both TM and TE polarizations of
      light. We demonstrate that dielectric dimers allow us to simultaneously achieve
      pure magnetic and electric near-field hotspots for both polarizations in contrast
      to plasmonic structures. This offers new approaches for near-field engineering
      such as sensing, control of spontaneous emission, and enhanced Raman scattering. 

PMID- 25773045
TI  - RyR2 Common Gene Variant G1886S and the Risk of Ventricular Arrhythmias in ICD
      Patients with Heart Failure.
AB  - BACKGROUND: Cardiac ryanodine receptor 2 (RyR2) is critical to the electrical
      homeostasis of cardiomyocytes. Its gene variant rs3766871 entails channel
      destabilization and enhanced intracellular Ca(2+) oscillation, thus promoting
      cardiac arrhythmias. We investigated whether the RyR2 rs3766871 variant is
      associated with aborted sudden cardiac death or ICD therapy for ventricular
      tachycardia (VT)/fibrillation (VF) in heart failure (HF) patients implanted with
      a cardioverter defibrillator (ICD). METHODS AND RESULTS: A total of 183 HF
      patients with primary or secondary prevention ICD were divided in 2 groups. A
      VT/VF group was composed of secondary prevention patients and primary prevention
      patients with appropriate ICD intervention for VT/VF. An ICD control group was
      composed of primary prevention patients free from any appropriate ICD
      intervention after 43 +/- 25 months follow-up. Study subjects were genotyped with
      respect to the rs3766871 RyR2 gene variant. Hazard ratios (HRs) were derived from
      Cox proportional-hazards regression analysis. In all, 56 patients constituted the
      VT/VF group and 127 patients the ICD control group. Male sex (HR: 3.02; 95% CI:
      0.99-9.18; P = 0.05), atrial fibrillation (AF; HR: 2.33; 95% CI: 0.89-6.10; P =
      0.08), and underuse of beta-blockers (HR: 2.08; 95% CI: 0.84-5.15; P = 0.11) were
      associated with the VT/VF phenotype. Prevalence of the rs3766871 minor allele was
      2.8% in ICD control patients and 8.0% in the VT/VF group (P = 0.02). After
      adjustment for age, sex, AF, and use of beta-blockers, the rs3766871 minor allele
      was associated with increased risk of VT/VF (HR: 3.49; 95% CI: 1.14-10.62; P =
      0.02). CONCLUSIONS: Our study identifies a significant role of RyR2 rs3766871
      minor allele for increased susceptibility to VT/VF in a population of ICD
      patients with HF.

PMID- 25773046
TI  - The effect of teriparatide to alleviate pain and to prevent vertebral collapse
      after fresh osteoporotic vertebral fracture.
AB  - Vertebral fracture is often seen in osteoporotic patients. Teriparatide is
      expected to promote bone union. Therefore, we evaluated the action of vertebral
      collapse prevention by administering teriparatide to vertebral fracture patients.
      Thirty-four patients with fresh vertebral fracture (48 vertebrae) participated in
      this study. They were administered either teriparatide (daily 20 ug/day or weekly
      56.5 ug/week) or risedronate (17.5 mg/week): ten patients (20 vertebrae) received
      teriparatide daily (Daily group), 11 patients (15 vertebrae) received
      teriparatide weekly (Weekly group), and 13 patients (14 vertebrae) received
      risedronate (RIS group). We compared some laboratory examination items, visual
      analogue scale (VAS) of low back pain, vertebral collapse rate and local kyphotic
      angle, and the cleft frequency. In addition, we evaluated 22 vertebral fracture
      patients (24 vertebrae) who did not take any osteoporotic medicines (Control
      group). There was no significant difference in any of the scores at the start of
      treatment. At 8 and 12 weeks after the initial visit, VAS scores in the Daily and
      Weekly groups were significantly lower than in the RIS group (p < 0.05). At 8 and
      12 weeks, the vertebral collapse rate and local kyphotic angle in the Daily group
      were significantly lower than in the RIS and Control groups (p < 0.01 and p <
      0.05, respectively), and those in the Weekly group were significantly lower than
      in the Control group (p < 0.05). The cleft frequency in the Daily group was
      significantly lower than in the RIS group (p < 0.05). Teriparatide is promising
      for the prevention of vertebral collapse progression after vertebral fracture.

PMID- 25773047
TI  - Bone matrix calcification during embryonic and postembryonic rat calvarial
      development assessed by SEM-EDX spectroscopy, XRD, and FTIR spectroscopy.
AB  - Bone mineral is constituted of biological hydroxyapatite crystals. In developing
      bone, the mineral crystal matures and the Ca/P ratio increases. However, how an
      increase in the Ca/P ratio is involved in maturation of the crystal is not known.
      The relationships among organic components and mineral changes are also unclear.
      The study was designed to investigate the process of calcification during rat
      calvarial bone development. Calcification was evaluated by analyzing the atomic
      distribution and concentration of Ca, P, and C with scanning electron microscopy
      (SEM)-energy-dispersive X-ray (EDX) spectroscopy and changes in the crystal
      structure with X-ray diffraction (XRD) and Fourier transform infrared (FTIR)
      spectroscopy. Histological analysis showed that rat calvarial bone formation
      started around embryonic day 16. The areas of Ca and P expanded, matching the
      region of the developing bone matrix, whereas the area of C became localized
      around bone. X-ray diffraction and FTIR analysis showed that the amorphous-like
      structure of the minerals at embryonic day 16 gradually transformed into poorly
      crystalline hydroxyapatite, whereas the proportion of mineral to protein
      increased until postnatal week 6. FTIR analysis also showed that crystallization
      of hydroxyapatite started around embryonic day 20, by which time SEM-EDX
      spectroscopy showed that the Ca/P ratio had increased and the C/Ca and C/P ratios
      had decreased significantly. The study suggests that the Ca/P molar ratio
      increases and the proportion of organic components such as proteins of the bone
      matrix decreases during the early stage of calcification, whereas crystal
      maturation continues throughout embryonic and postembryonic bone development. 

PMID- 25773048
TI  - Incidence of hip fracture in Niigata, Japan in 2004 and 2010 and the long-term
      trends from 1985 to 2010.
AB  - We investigated the incidence of hip fracture in a population of patients >=50
      years old in 2004 and 2010 in Niigata City, Niigata Prefecture, Japan. We also
      investigated the long-term trends in the incidence of hip fracture from 1985 to
      2010, using our previously reported survey results obtained from 1985 to 1999. In
      2004 and 2010, the survey found 2,368 and 3,218 proximal femur fractures,
      respectively. The crude hip fracture incidence rates in 2004 and 2010 were 215.8
      and 281.5 per 100,000 of population per year, respectively. For males, the
      incidence rates were 99.9 in 2004 and 126.3 in 2010; for females, the incidence
      rates were 311.0 and 410.7, respectively. In males aged 80-84 years, the
      incidence rate since 1999 has been decreasing, while that for males >85 years
      peaked in 2004. In females of all ages, the incidence rate was higher in 2010
      than in all other survey periods, and in females >85 years, the incidence has
      increased the fastest. Additionally, the long-term changes in the age- and sex
      standardized incidence each year using the 1985 population structure in Japan in
      females has been increasing, although it decreased in 1999. However, in males,
      the incidence in 2010 was not significantly different from that in 1994, although
      it has been increasing since 1999. Our study findings indicate that the age
      specific incidence of hip fractures in the Niigata Prefecture of Japan has not
      plateaued in females, but that it may have done so in males; in addition, the
      number and incidence of hip fractures has been increasing.

PMID- 25773049
TI  - Lessons from state mandates of preventive cancer screenings.
AB  - We use the 1997-2008 Medical Expenditure Panel Survey (MEPS) and variation in the
      timing of state mandates for coverage of colorectal, cervical, and prostate
      cancer screenings to investigate the behavioral and financial effects of mandates
      on privately insured adults. We find that state mandates did not result in
      increased rates of cancer screening. However, coverage of preventive care,
      whether mandated or not, moves the cost of care from the consumer's out-of-pocket
      expense to the premium, resulting in a cross-subsidy of users of the service by
      non-users. While some cross-subsidies are intentional, others may be
      unintentional. We find that users of cancer screening have higher levels of
      income and education, while non-users tend to be racial minorities, lack a usual
      source of care, and live in communities with fewer physicians per capita. These
      results suggest that coverage of preventive care may transfer resources from more
      advantaged individuals to less advantaged individuals. 

PMID- 25773050
TI  - The impact of non-financial and financial encouragements on participation in non
      school-based human papillomavirus vaccination: a retrospective cohort study.
AB  - OBJECTIVE: Adolescent vaccination coverage under a system of non school-based
      vaccination is likely to be suboptimal, but might be increased by targeted
      encouragement campaigns. We analysed the effect on human papillomavirus (HPV)
      vaccination initiation by girls aged 12-18 of two campaigns set up in Flanders
      (Belgium) in 2007 and 2009: a personal information campaign and a combined
      personal information and financial incentive campaign. METHODS: We analysed
      (objective) data on HPV vaccination behaviour from the National Alliance of
      Christian Mutualities (NACM), Flanders' largest sickness fund. We used z-scores
      to compare the monthly proportion of girls initiating HPV vaccination over time
      between carefully selected intervention and control groups. Separate analyses
      were done for older and younger girls. Total sample sizes of the intervention
      (control) groups were 221 (243) for the personal information campaign and 629
      (5,322) for the combined personal information and financial incentive campaign.
      RESULTS: The personal information campaign significantly increased vaccination
      initiation, with older girls reacting faster. One year after the campaign the
      percentages of vaccination initiation for the oldest girls were 64.6 and 42.8 %
      in the intervention and control group, respectively (z = 3.35, p = 0.0008); for
      the youngest girls the percentages were 78.4 and 68.1 % (z = 1.71, p = 0.09). The
      combined personal information and financial incentive campaign increased
      vaccination initiation among certain age groups. One year after the campaign the
      difference in percentage points for HPV vaccination initiation between
      intervention and control groups varied between 18.5 % (z = 3.65, p = 0.0002) and
      5.1 % (z = 1.12, p = 0.26). CONCLUSION: Under a non school-based vaccination
      system, personal information and removing out-of-pocket costs had a significant
      positive effect on HPV vaccination initiation, although the effect substantially
      varied in magnitude. Overall, the obtained vaccination rates remained far below
      those realised under school-based HPV vaccination.

PMID- 25773051
TI  - Direct in situ observation of metallic glass deformation by real-time nano-scale
      indentation.
AB  - A common understanding of plastic deformation of metallic glasses (MGs) at room
      temperature is that such deformation occurs via the formation of runaway shear
      bands that usually lead to catastrophic failure of MGs. Here we demonstrate that
      inhomogeneous plastic flow at nanoscale can evolve in a well-controlled manner
      without further developing of shear bands. It is suggested that the sample
      undergoes an elasto-plastic transition in terms of quasi steady-state localized
      shearing. During this transition, embryonic shear localization (ESL) propagates
      with a very slow velocity of order of ~1 nm/s without the formation of a hot
      matured shear band. This finding further advances our understanding of the
      microscopic deformation process associated with the elasto-plastic transition and
      may shed light on the theoretical development of shear deformation in MGs.

PMID- 25773052
TI  - Acute hyperhydration reduces athlete biological passport OFF-hr score.
AB  - Anecdotal evidence suggests that athletes hyperhydrate to mask prohibited
      substances in urine and potentially counteract suspicious fluctuations in blood
      parameters in the athlete biological passport (ABP). It is examined if acute
      hyperhydration changes parameters included in the ABP. Twenty subjects received
      recombinant human erythropoietin (rhEPO) for 3 weeks. After 10 days of rhEPO
      washout, 10 subjects ingested normal amount of water (~ 270 mL), whereas the
      remaining 10 ingested a 1000 mL bolus of water. Blood variables were measured 20,
      40, 60, and 80 min after ingestion. Three days later, the subjects were crossed
      over with regard to water ingestion and the procedure was repeated. OFF-hr was
      reduced by ~ 4%, ~ 3%, and ~ 2% at 40, 60, and 80 min, respectively, after
      drinking 1000 mL of water, compared with normal water ingestion (P < 0.05). Forty
      percent of the subjects were identified with atypical blood profiles (99%
      specificity level) before drinking 1000 mL of water, whereas 11% (n = 18), 10%
      and 11% (n = 18) were identified 40, 60, and 80 min, respectively, after
      ingestion. This was different (P < 0.05) compared with normal water intake, where
      45% of the subjects were identified before ingestion, and 54% (n = 19), 45%, and
      47% (n = 19) were identified 40, 60, and 80 min, respectively, after ingestion.
      In conclusion, acute hyperhydration reduces ABP OFF-hr and reduces ABP
      sensitivity.

PMID- 25773053
TI  - THE EFFECT OF STATE INSURANCE MANDATES ON INFANT IMMUNIZATION RATES.
AB  - While US infant immunization rates have been increasing in the last 20 years, the
      cost of fully immunizing a child with all recommended vaccines has almost
      tripled. This is partly not only due to new additions in the list of recommended
      vaccines but also due to the use of new, safer, but more expensive technologies
      in vaccine production and distribution. In recent years, many states have
      mandated that recommended childhood vaccines be covered by private health
      insurance companies. Currently, there are 33 states with such a mandate. In this
      paper, I examine whether the introduction of mandates on private insurers
      affected immunization rates. Using state and time variation, I find that mandates
      increased the immunization rate for three vaccines--the diphtheria-tetanus
      pertussis, polio, and measles-mumps-rubella vaccines--by about 1.8 percentage
      points. These results may provide a lower bound for the expected effect of the
      Affordable Care Act, which mandates coverage of childhood vaccines for all
      private insurers in the USA. I also find evidence that the mandates shifted a
      significant portion of vaccinations from publicly funded sources to private ones,
      with a decline in public health clinic visits and an increase in vaccinations at
      hospitals and doctor's offices.

PMID- 25773054
TI  - Leukotriene inhibitors for bronchiolitis in infants and young children.
AB  - BACKGROUND: Bronchiolitis is an acute inflammatory illness of the bronchioles
      common among infants and young children. It is often caused by the respiratory
      syncytial virus (RSV). Management of bronchiolitis varies between clinicians,
      reflecting the lack of evidence for a specific treatment approach. The
      leukotriene pathway has been reported to be involved in the pathogenesis of
      bronchiolitis. Leukotriene inhibitors such as montelukast have been used in
      infants and young children with bronchiolitis. However, the results from limited
      randomised controlled trials (RCTs) are controversial and necessitate a thorough
      evaluation of their efficacy for bronchiolitis in infants and young children.
      OBJECTIVES: To assess the efficacy and safety of leukotriene inhibitors for
      bronchiolitis in infants and young children. SEARCH METHODS: We searched CENTRAL
      (2014, Issue 5), MEDLINE (1946 to April week 4, 2014), EMBASE (1974 to May 2014),
      CINAHL (1981 to May 2014), LILACS (1982 to May 2014), Web of Science (1985 to May
      2014), WHO ICTRP and ClinicalTrials.gov (6 May 2014). SELECTION CRITERIA: RCTs
      comparing leukotriene inhibitors versus placebo or another intervention in
      infants and young children under two years of age diagnosed with bronchiolitis.
      Our primary outcomes were length of hospital stay and all-cause mortality.
      Secondary outcomes included clinical severity score, percentage of symptom-free
      days, percentage of children requiring ventilation, oxygen saturation, recurrent
      wheezing, respiratory rate and clinical adverse effects. DATA COLLECTION AND
      ANALYSIS: We used standard Cochrane Collaboration methodological practices. Two
      authors independently assessed trial eligibility and extracted data, such as
      general information, participant characteristics, interventions and outcomes. We
      assessed risk of bias and graded the quality of the evidence. We used Review
      Manager software to pool results and chose random-effects models for meta
      analysis. MAIN RESULTS: We included five studies with a total of 1296
      participants under two years of age hospitalised with bronchiolitis. Two studies
      with low risk of bias compared 4 mg montelukast (a leukotriene inhibitor) daily
      use from admission until discharge with a matching placebo. Both selected length
      of hospital stay as a primary outcome and clinical severity score as a secondary
      outcome. However, the effects of leukotriene inhibitors on length of hospital
      stay and clinical severity score were uncertain due to considerable heterogeneity
      between the study results and wide confidence intervals around the estimated
      effects (hospital stay: mean difference (MD) -0.95 days, 95% confidence interval
      (CI) -3.08 to 1.19, P value = 0.38, low quality evidence; clinical severity score
      on day two: MD -0.57, 95% CI -2.37 to 1.23, P value = 0.53, low quality evidence;
      clinical severity score on day three: MD 0.17, 95% CI -1.93 to 2.28, P value =
      0.87, low quality evidence). The other three studies compared montelukast for
      several weeks for preventing post-bronchiolitis symptoms with placebo. We
      assessed one study as low risk of bias, whereas we assessed the other two studies
      as having a high risk of attrition bias. Due to the significant clinical
      heterogeneity in severity of disease, duration of treatment, outcome measurements
      and timing of assessment, we did not pool the results. Individual analyses of
      these studies did not show significant differences between the leukotriene
      inhibitors group and the control group in symptom-free days and incidence of
      recurrent wheezing. One study of 952 children reported two deaths in the
      leukotriene inhibitors group: neither was determined to be drug-related. No data
      were available on the percentage of children requiring ventilation, oxygen
      saturation and respiratory rate. Finally, three studies reported adverse events
      including diarrhoea, wheezing shortly after administration and rash. No
      differences were reported between the study groups. AUTHORS' CONCLUSIONS: The
      current evidence does not allow definitive conclusions to be made about the
      effects of leukotriene inhibitors on length of hospital stay and clinical
      severity score in infants and young children with bronchiolitis. The quality of
      the evidence was low due to inconsistency (unexplained high levels of statistical
      heterogeneity) and imprecision arising from small sample sizes and wide
      confidence intervals, which did not rule out a null effect or harm. Data on
      symptom-free days and incidence of recurrent wheezing were from single studies
      only. Further large studies are required. We identified one registered ongoing
      study, which may make a contribution in the updates of this review.

PMID- 25773055
TI  - Correction to "Controlling structure and porosity in catalytic nanoparticle
      superlattices with DNA".

PMID- 25773056
TI  - Walking Pattern in COPD Patients.
AB  - PURPOSE: To compare the activity and walking pattern of individuals with chronic
      obstructive pulmonary disease (COPD) and control subjects during a 24-hour
      period. DESIGN: Cross-sectional study in home and community. METHODS: The average
      walking velocity, time spent in sitting, standing, and lying, and numbers of
      steps per 24 hours were measured in nine individuals with COPD and eight healthy
      control subjects. FINDINGS: The average walking velocity in individuals with COPD
      was equivalent to that of the control subjects. Individuals with COPD walked
      significantly less than the control subjects. The total time spent sitting,
      standing, and walking was similar in the two groups. CONCLUSIONS: The results
      suggested that the walking velocity selected by individuals with COPD serves to
      minimize energy cost per distance. CLINICAL RELEVANCE: The study findings
      emphasize the need to maintain walking velocity in any exercise prescription for
      individuals with COPD.

PMID- 25773057
TI  - Dynein motors: How AAA+ ring opening and closing coordinates microtubule binding
      and linker movement.
AB  - Dyneins are a family of motor proteins that move along the microtubule. Motility
      is generated in the motor domain, which consists of a ring of six AAA+ (ATPases
      associated with diverse cellular activities) domains, the linker and the
      microtubule-binding domain (MTBD). The cyclic ATP-hydrolysis in the AAA+ ring
      causes the remodelling of the linker, which creates the necessary force for
      movement. The production of force has to be synchronized with cycles of
      microtubule detachment and rebinding to efficiently create movement along the
      microtubule. The analysis of four dynein motor domain crystal structures in the
      essay presented here provides evidence that this crucial coordination is carried
      out by open/closed AAA+ ring conformations. 

PMID- 25773058
TI  - Cross-fostering in gray wolves (Canis lupus lupus).
AB  - Cross-fostering in canids, with captive-bred pups introduced into endangered wild
      populations, might aid conservation efforts by increasing genetic diversity and
      lowering the risk of inbreeding depression. The gray wolf (Canis lupus lupus)
      population in Scandinavia suffers from severe inbreeding due to a narrow genetic
      base and geographical isolation. This study aimed at evaluating the method to
      cross-foster wolf pups from zoo-born to zoo-born litters. The following was
      assessed: female initial acceptance of foster pups, growth rate in relation to
      age difference between foster pups and pups in recipient litters and survival
      over the first 33 weeks. The study included four litters added by two foster pups
      in each. The age differences between the foster pups and the recipient litters
      were 2-8 days. After augmentation, all four females accepted the foster pups,
      demonstrated by her moving the entire litter to a new den site. Growth rate was
      dependent on the age difference of the pups in the foster litters, with a
      considerably slower growth rate in the 8 days younger pups. However, these pups
      later appeared to be at no disadvantage. Foster pups had a higher survival rate
      than females' pups, however, the causes of death were probably not kin or non-kin
      related. The results indicate that cross-fostering works in gray wolves and that
      this might be a plausible way to increase genetic variation in the wild
      population.

PMID- 25773059
TI  - Osseous characteristics of mice lacking cannabinoid receptor 2 after pulp
      exposure.
AB  - INTRODUCTION: Endogenous cannabinoid compounds are involved in many physiological
      processes, including bone metabolism. Cannabinoid receptor 2 (CB2) plays a role
      in modulating bone density, but published research results are conflicting.
      Furthermore, the specific role of CB2 in inflammation-induced bone resorption and
      craniofacial bone density has not been reported. The objective of this study was
      to assess the role of CB2 in dental pulp exposure-induced periapical bone loss
      and mandibular bone density. METHODS: Adult female wild-type (WT) and CB2
      homozygous knockout (KO) mice were used. Pulp exposures were created unilaterally
      in the mandibular first molars, and the pulp was left exposed to the oral cavity
      to induce periapical lesion formation. Mandibles were harvested 26 days after
      pulp exposure. Mandibular bone mineral density and periapical lesion volume were
      assessed using micro-computed tomographic imaging. RESULTS: Periapical lesion
      volume measured on the mesial root of the pulp-exposed first molar was
      significantly less in CB2 KO than WT mice (P < .05). No significant difference
      was detected between KO and WT mice in the size of the PDL space measured on the
      mesial root of the contralateral intact first molar. CB2 KO mice exhibited
      greater mandibular bone density than WT mice (P < .05). CONCLUSIONS: CB2 plays a
      role in mandibular bone metabolism. Increased bone density in CB2 KO mice may
      contribute to the smaller periapical lesion size observed after pulp exposure in
      KO compared with WT mice. Additional experiments are needed to further elucidate
      the function of CB2 and clinical implications of cannabinoids on bone and
      periapical pathosis.

PMID- 25773061
TI  - Clinical outcomes with bevacizumab-containing and non-bevacizumab-containing
      regimens in patients with recurrent glioblastoma from US community practices.
AB  - This analysis evaluated the efficacy and safety of bevacizumab as monotherapy and
      with irinotecan for recurrent glioblastoma in community-based practices. Adult
      patients with bevacizumab-naive, recurrent glioblastoma initiating second-line
      treatment (July 2006-June 2010) were identified using McKesson Specialty
      Health/US Oncology Network health records. Overall (OS) and progression-free
      survival (PFS) estimates were analyzed through July 2011 and compared for
      bevacizumab and non-bevacizumab regimens using the log-rank test. An adjusted Cox
      proportional hazards model assessed the effects of patient and treatment
      characteristics on outcomes. The analysis identified 159 patients initiating
      second-line treatment with a bevacizumab-monotherapy (n = 57), bevacizumab
      combination (n = 79), or non-bevacizumab (n = 23) regimen. Patient
      characteristics were generally similar across groups. In the Cox analyses, OS
      (hazard ratio [HR] 0.51 [95 % confidence interval (CI) 0.31-0.82]; univariate
      medians: 8.86 vs. 5.19 months) was significantly longer with bevacizumab
      containing regimens. Median PFS was longer with bevacizumab-containing regimens,
      but did not reach statistical significance (HR 0.64 [95 % CI 0.38-1.09];
      univariate medians: 7.00 vs. 4.00 months). Analyses showed that each bevacizumab
      treatment group relative to non-bevacizumab had a reduced risk of death
      (bevacizumab-monotherapy regimen: HR 0.56 [95 % CI 0.31-1.03] and bevacizumab
      combination regimen: HR 0.34 [95 % CI 0.21-0.68]). Patients receiving the
      bevacizumab-combination regimen trended toward longer OS and PFS than those
      receiving the bevacizumab-monotherapy regimen. Rates of bevacizumab-related
      toxicities were consistent with clinical trial reports.

PMID- 25773062
TI  - MRI perfusion measurements calculated using advanced deconvolution techniques
      predict survival in recurrent glioblastoma treated with bevacizumab.
AB  - Bevacizumab is a therapeutic drug used in treatment of recurrent glioblastoma to
      inhibit angiogenesis. Treatment response is often monitored through the use of
      perfusion MRI measures of cerebral blood volume, flow, and other pharmacokinetic
      parameters; however, most methods for deriving these perfusion parameters can
      produce errors depending on bolus kinetics. Recently, a number of new methods
      have been developed to overcome these challenges. In the current study we examine
      cerebral blood volume and blood flow characteristics in 45 recurrent glioblastoma
      patients before and after treatment with bevacizumab. Perfusion MRI data was
      processed using a standard single value decomposition (SVD) technique, two block
      circulant SVD techniques, and a Bayesian estimation technique. A proportional
      hazards model showed that patients with a large decrease in relative blood volume
      (RBV) after treatment had extended overall survival (P = 0.0048). Patients with
      large pre-treatment relative blood flow (RBF) showed extended progression-free
      survival (P = 0.0216) and overall survival (P = 0.0112), and patients with a
      large decrease in RBF following treatment showed extended overall survival (P =
      0.0049). These results provide evidence that blood volume and blood flow
      measurements can be used as biomarkers in patients treated with bevacizumab.

PMID- 25773063
TI  - CD4 T Cells but Not Th17 Cells Are Required for Mouse Lung Transplant
      Obliterative Bronchiolitis.
AB  - Lung transplant survival is limited by obliterative bronchiolitis (OB), but the
      mechanisms of OB development are unknown. Previous studies in a mouse model of
      orthotopic lung transplantation suggested a requirement for IL-17. We have used
      this orthotopic mouse model to investigate the source of IL-17A and the
      requirement for T cells producing IL-17A. The major sources of IL-17A were CD4(+)
      T cells and gammadelta T cells. Depletion of CD4(+) T cells led to a
      significantly decreased frequency and number of IL-17A(+) lymphocytes and was
      sufficient to prevent acute rejection and OB. However, mice with STAT3-deficient
      T cells, which are unable to differentiate into Th17 cells, rejected lung
      allografts and developed OB similar to control mice. The frequency of IL-17A(+)
      cells was not decreased in mice with STAT3-deficient T cells due mainly to the
      presence of IL-17A(+) gammadelta T cells. Deficiency of gammadelta T cells also
      did not affect the development of airway fibrosis. Our data suggest that CD4(+) T
      cells are required for OB development and expansion of IL-17A responses in the
      lung, while Th17 and gammadelta T cells are not absolutely required and may
      compensate for each other. 

PMID- 25773064
TI  - Uric acid crystal could inhibit Numb-induced URAT1 lysosome degradation in uric
      acid nephropathy.
AB  - To investigate whether uric acid could regulate urate transporter 1 (URAT1)
      protein and activity level, we established uric acid nephropathy (UAN) rat model
      and detected their serum uric acid and URAT1 level with or without the treatment
      of allopurinol. Results here showed that allopurinol could reduce serum uric acid
      level in UAN rat model. We further found that in UAN rats, the total and surface
      URAT1 expression level were both increased while this increase could be blocked
      by allopurinol treatment. By treating URAT1 stable expressed HEK cell with
      monosodium urate (MSU) crystals, we found that URAT1 level showed an increase in
      both total and cell surface level, and it would colocalize more with Rab11
      instead of Rab7. Consistently, we also found that the total URAT1 protein level
      will show an increase in the presence of lysosome inhibitors but not ubiquitin
      proteasome inhibitors. Furthermore, we also found that MSU crystal could drive
      Numb, a clathrin-coated adaptor protein which performs a key function in cell
      division, out of cell surface and disassociated it from URAT1. Finally, we found
      that Numb short hairpin RNA (shRNA)-transfected showed a phenocopy as MSU
      treatment, while Numb-2A mutation over-expression could resist crystal-induced
      phenotypes. These findings indicated that uric acid crystal could increase URAT1
      membrane distribution through inhibiting Numb-induced URAT1 lysosome degradation.

PMID- 25773065
TI  - Bridging the racial gap. National trend in african-american women breast cancer
      research productivity from 1992 to 2012.

PMID- 25773066
TI  - True boundary for the formation of homoleptic transition-metal hydride complexes.
AB  - Despite many exploratory studies over the past several decades, the presently
      known transition metals that form homoleptic transition-metal hydride complexes
      are limited to the Groups 7-12. Here we present evidence for the formation of Mg3
      CrH8 , containing the first Group 6 hydride complex [CrH7 ](5-) . Our theoretical
      calculations reveal that pentagonal-bipyramidal H coordination allows the
      formation of sigma-bonds between H and Cr. The results are strongly supported by
      neutron diffraction and IR spectroscopic measurements. Given that the Group 3-5
      elements favor ionic/metallic bonding with H, along with the current results, the
      true boundary for the formation of homoleptic transition-metal hydride complexes
      should be between Group 5 and 6. As the H coordination number generally tends to
      increase with decreasing atomic number of transition metals, the revised boundary
      suggests high potential for further discovery of hydrogen-rich materials that are
      of both technological and fundamental interest.

PMID- 25773067
TI  - Aging induced cortical drive alterations during sleep in rats.
AB  - We followed the impact of healthy aging on cortical drive during sleep in rats by
      using the corticomuscular coherence (CMC). We employed the chronic electrodes
      implantation for sleep recording in adult, male Wistar rats, and followed the
      aging impact during sleep from 3 to 5.5 months age. We have analyzed the
      sleep/wake states architecture, and the sleep/wake state related EEG
      microstructure and CMCs. We evidenced the topographically distinct impact of
      aging on sleep/wake states architecture within the sensorimotor (SMCx) vs. motor
      cortex (MCx) from 4.5 to 5.5 months age. Healthy aging consistently altered only
      the SMCx sleep/wake states architecture, and increased the delta and beta CMCs
      through both cortical drives during Wake, but only through the MCx drive during
      REM. According to the delta and beta CMCs values, aging impact through the SMCx
      drive was opposite, but it was convergent through the MCx drive during Wake vs.
      REM, and there was a dual and inverse mode for the motor control during REM.

PMID- 25773068
TI  - Exposure to secondhand tobacco smoke and the frailty syndrome in US older adults.
AB  - Exposure to secondhand tobacco smoke (SHS) is a well-established risk factor for
      cardiovascular disease and lung cancer in nonsmoking adults. However, few studies
      have focused on the health consequences of exposure to SHS in older adults. This
      is the first study to assess the association between SHS and the frailty syndrome
      in the nonsmoking older adult population. Cross-sectional study was conducted
      among 2059 nonsmoking adults aged >=60 years who participated in the third US
      National Health and Nutrition Examination Survey and had completed a physical
      examination. Exposure to SHS was assessed by serum cotinine concentrations and by
      self-reported data from the home questionnaire. Frailty was ascertained with a
      slight modification of the Fried criteria. Analyses were performed with logistic
      regression and adjusted for the main confounders. The median (interquartile
      range) concentration of serum cotinine was 0.095 (IQR 0.035-0.211) ng/mL. The
      prevalence of frailty was 6.0 %. The odds ratios (95 % confidence interval [CI])
      of frailty comparing the second, third, and fourth to the lowest quartile of
      serum cotinine were, respectively, 1.44 (0.67-3.06), 1.46 (0.75-2.85), and 2.51
      (1.06-5.95), p value for trend 0.04. An increased frequency of frailty was also
      observed in participants reporting to live with >=2 smokers at home (odds ratio
      5.37; 95 % CI 1.13-25.5). In the US nonsmoking older adult population, exposure
      to SHS was associated with an increased frequency of frailty. More efforts are
      needed to protect older adults from SHS, especially at home and in other areas
      not covered by smoke-free regulations.

PMID- 25773069
TI  - Impact of low-volume, high-intensity interval training on maximal aerobic
      capacity, health-related quality of life and motivation to exercise in ageing
      men.
AB  - There is a demand for effective training methods that encourage exercise
      adherence during advancing age, particularly in sedentary populations. This study
      examined the effects of high-intensity interval training (HIIT) exercise on
      health-related quality of life (HRQL), aerobic fitness and motivation to exercise
      in ageing men. Participants consisted of males who were either lifelong sedentary
      (SED; N = 25; age 63 +/- 5 years) or lifelong exercisers (LEX; N = 19; aged 61 +/
      5 years). [Formula: see text] and HRQL were measured at three phases: baseline
      (Phase A), week seven (Phase B) and week 13 (Phase C). Motivation to exercise was
      measured at baseline and week 13. [Formula: see text] was significantly higher in
      LEX (39.2 +/- 5.6 ml kg min(-1)) compared to SED (27.2 +/- 5.2 ml kg min(-1)) and
      increased in both groups from Phase A to C (SED 4.6 +/- 3.2 ml kg min(-1), 95 %
      CI 3.1 - 6.0; LEX 4.9 +/- 3.4 ml kg min(-1), 95 % CI 3.1-6.6) Physical
      functioning (97 +/- 4 LEX; 93 +/- 7 SED) and general health (70 +/- 11 LEX; 78 +/
      11 SED) were significantly higher in LEX but increased only in the SED group
      from Phase A to C (physical functioning 17 +/- 18, 95 % CI 9-26, general health
      14 +/- 14, 95 % CI 8-21). Exercise motives related to social recognition (2.4 +/-
      1.2 LEX; 1.5 +/- 1.0 SED), affiliation (2.7 +/- 1.0 LEX; 1.6 +/- 1.2 SED) and
      competition (3.3 +/- 1.3 LEX; 2.2 +/- 1.1) were significantly higher in LEX yet
      weight management motives were significantly higher in SED (2.9 +/- 1.1 LEX; 4.3
      +/- 0.5 SED). The study provides preliminary evidence that low-volume HIIT
      increases perceptions of HRQL, exercise motives and aerobic capacity in older
      adults, to varying degrees, in both SED and LEX groups.

PMID- 25773071
TI  - The UK general election: a manifesto for health.

PMID- 25773072
TI  - International Women's Day 2015.

PMID- 25773073
TI  - COPD: improving prevention and care.

PMID- 25773070
TI  - ANGPTL2 increases bone metastasis of breast cancer cells through enhancing CXCR4
      signaling.
AB  - Bone metastasis of breast cancer cells is a major concern, as it causes increased
      morbidity and mortality in patients. Bone tissue-derived CXCL12 preferentially
      recruits breast cancer cells expressing CXCR4 to bone metastatic sites. Thus,
      understanding how CXCR4 expression is regulated in breast cancer cells could
      suggest approaches to decrease bone metastasis of breast tumor cells. Here, we
      show that tumor cell-derived angiopoietin-like protein 2 (ANGPTL2) increases
      responsiveness of breast cancer cells to CXCL12 by promoting up-regulation of
      CXCR4 in those cells. In addition, we used a xenograft mouse model established by
      intracardiac injection of tumor cells to show that ANGPTL2 knockdown in breast
      cancer cells attenuates tumor cell responsiveness to CXCL12 by decreasing CXCR4
      expression in those cells, thereby decreasing bone metastasis. Finally, we found
      that ANGPTL2 and CXCR4 expression levels within primary tumor tissues from breast
      cancer patients are positively correlated. We conclude that tumor cell-derived
      ANGPTL2 may increase bone metastasis by enhancing breast tumor cell
      responsiveness to CXCL12 signaling through up-regulation of tumor cell CXCR4
      expression. These findings may suggest novel therapeutic approaches to treat
      metastatic breast cancer. 

PMID- 25773074
TI  - Next UK Government must trust in NHS staff and local solutions.

PMID- 25773077
TI  - UK NHS staff: stressed, exhausted, burnt out.

PMID- 25773078
TI  - Working towards an end to FGM.

PMID- 25773081
TI  - Dainius Puras: UN Special Rapporteur on the right to health.

PMID- 25773082
TI  - Development with values: lessons from Bhutan.

PMID- 25773083
TI  - Jean Lindenmann.

PMID- 25773085
TI  - Immigration Act 2014 challenges health of migrants in the UK.

PMID- 25773084
TI  - Working together for excellence in the NHS: student proposals.

PMID- 25773086
TI  - Embed a public health ethos in the medical workforce.

PMID- 25773087
TI  - Organ transplantation in China: concerns remain.

PMID- 25773088
TI  - Organ transplantation in China: concerns remain.

PMID- 25773089
TI  - Organ transplantation in China: concerns remain.

PMID- 25773090
TI  - Organ transplantation in China: concerns remain.

PMID- 25773091
TI  - Organ transplantation in China: concerns remain.

PMID- 25773095
TI  - Organ transplantation in China: concerns remain.

PMID- 25773096
TI  - Central retinal vein occlusion with bilateral stenosis of the internal carotid
      arteries.

PMID- 25773097
TI  - French health workers strike over payment plan in health bill.

PMID- 25773098
TI  - The Commission on Narcotic Drugs' attempt to restrict ketamine.

PMID- 25773100
TI  - Editorial.

PMID- 25773101
TI  - AAO-HNS Intl Tinnitus Miniseminar Summary 2014.

PMID- 25773102
TI  - Factors affecting severity of tinnitus - a follow-up study of tinnitus subjects
      at an Ear Nose Throat clinic in Sweden.
AB  - OBJECTIVE: The aim of the present study was to examine whether perceived tinnitus
      severity changes over time, and if so what factors contribute to this change.
      DESIGN: A modified Swedish version of tinnitus severity questionnaire (MS-TSQ)
      was used to examine changes in tinnitus severity over a period of time. STUDY
      SAMPLE: The MS-TSQ questionnaire was completed by 455 subjects visiting an Ear,
      Nose and Throat (ENT) clinic in Sweden as part of baseline assessment (Sb). The
      same questionnaire was completed during follow-up assessment (Sf) by 174 of these
      subjects to examine changes in tinnitus severity, if any. The difference in
      scores obtained from the two assessments was calculated and was termed as
      difference scores (Sd). RESULTS: RESULTS of analyses of variance (ANOVA)
      indicated significant reduction in tinnitus severity from Sb to Sf scores (p <
      0.001). Subjects with noise induced hearing loss showed significantly lower Sd
      scores than subjects with unspecified sensorineural hearing loss (p < 0.01). The
      group who received psychological treatment for tinnitus obtained significantly
      higher Sd than those who did not (p < 0.01). CONCLUSIONS: RESULTS provide
      valuable framework for understanding the factors that affect tinnitus severity
      over a period of time.

PMID- 25773103
TI  - Effect of hormone replacement therapy on the auditory brainstem response of
      postmenopausal women.
AB  - OBJECTIVE: To investigate whether hormone replacement therapy modifies the
      auditory brainstem response in postmenopausal women. METHODS: Nineteen
      postmenopausal women received hormone replacement therapy (study group) and 25
      received no treatment nor placebo (control group). In both groups, age ranged
      from 45 to 60 years and pure-tone sensitivity was 25 dB or better at frequencies
      between 500 and 2000 Hz. Auditory brainstem response was evaluated before and
      after 3 months of hormone use in the study group. The control group was also
      evaluated at the same periods. The following auditory brainstem response
      parameters were compared between the two groups: latencies of waves I, III, and
      V; I-III, III-V, and I-V interpeak intervals. RESULTS: Mean age did not differ
      between groups (study group: 51.5 +/- 0.7 years; control: 52.9 +/- 0.6 years). No
      significant differences in wave latencies, or interpeak intervals were observed
      between the two groups (p > 0.05).

PMID- 25773104
TI  - Development and standardization of tinnitus handicap inventory in malayalam.
AB  - INTRODUCTION: Tinnitus is defined as the perception of sound mainly due to the
      activity within the central nervous system without any mechanical, vibratory
      activity within the cochlea. Administration of tinnitus related questionnaires
      along with the audiological test battery is recommended in routine clinical
      practice. Tinnitus Handicap Inventory (THI) is one of the useful and widely
      recognized tools for quantifying the impact of tinnitus on daily life. India,
      being a multilingual country with a multicultural background, there is no such
      inventories available in many of the local Indian languages except in Tamil and
      Kannada. MATERIALS & METHODS: The English THI was translated to Malayalam by a
      faculty who is qualified and proficient in Malayalam language. Then the
      translated THI was given to 40 native Malayalam speakers for content validity.
      The final THI-M was administered on 50 tinnitus patient. Obtained data was then
      subjected for statistical analysis using SPSS Statistics 17.0. RESULTS:
      Reliability statistics revealed an alpha score of 0.855 for the overall
      inventory. Across the three subscales, i.e. emotional, functional and
      catastrophic, a global alpha score of 0.766, 0.693 and 0.630, respectively. The
      alpha score remained the same even after deleting any single item. CONCLUSION:
      The results of the current study conclude that, THI-M has a good
      reliability/internal consistency as per the Cronbach's alpha score. THI-M can be
      considered as a reliable tool that can be used across the State by Hearing
      Professionals in assessment and management.

PMID- 25773105
TI  - The effect of a gluten-free diet on a patient complaining of severe tinnitus.
AB  - We report a case of a patient complaining of severe high pitched tinnitus,
      dizziness, joint/muscle pain and gastrointestinal symptoms. A mild high-frequency
      sensorineural hearing loss of cochlear origin was diagnosed in the ear where
      tinnitus was present. The patient reported a considerable decrease in tinnitus
      and other symptoms with a gluten-free diet. Gluten sensitivity may have
      contributed to the pathogenesis of tinnitus in our patient; further research is
      needed to determine the exact role of gluten in this condition. 

PMID- 25773106
TI  - Tinnitus in adolescents and its relation to the use of personal sound systems.
AB  - INTRODUCTION: References to recreational exposure to high sound pressure levels
      (SPL) and the risk of hearing loss and sensation of tinnitus has increased in the
      adolescent population. OBJECTIVE: To identify the occurrence of tinnitus in
      adolescents who use personal sound systems (PSS). MATERIAL AND METHODS: This was
      a descriptive cross-sectional study, using a sample of 153 normal-hearing
      adolescent students. Participants answered a self-adaministered questionnaire
      containing open and closed questions, addressing information regarding sound
      habits with the use of PSS and symptoms associated with this practice. RESULTS:
      The occurrence of a habit of using PSS was 93%. Comparing the exposed and
      unexposed groups, the incidence of tinnitus was 40% and 33% respectively, and 22%
      reported the occurrence of tinnitus induced by the use of PSS. There was no
      significant difference for the presence of tinnitus depending on the degree of
      exposure. CONCLUSION: Although no relation between the use of PSS with tinnitus
      has been observed, the prevalence of symptoms of up to 40%, including noise
      induced episodes, reinforces the possibility of subclinical hearing loss induced
      by high NPS and, because of the irreversible nature of these losses, the urgency
      of educational and regulatory measures to reverse these habits and attitudes.

PMID- 25773107
TI  - Is tinnitus acceptance the same as tinnitus habituation?
AB  - INTRODUCTION: Tinnitus habituation and tinnitus acceptance both describe an
      apparent lack of responding to tinnitus noise. However, no prior studies have
      evaluated the possible overlap between tinnitus habituation and acceptance
      processes in chronic tinnitus sufferers. OBJECTIVES: We examined responses to the
      seven acceptance items from the Tinnitus Response Scales (TRS) along with 19
      items that tapped the perceptual/behavioural aspects of tinnitus habituation.
      MATERIALS AND METHODS: A large sample of chronic tinnitus sufferers (n = 273)
      were recruited via advertisements placed at tinnitus clinics and websites and in
      the media. They were asked to complete an online survey asking about their
      tinnitus history and recent experiences of tinnitus habituation, sensitization to
      tinnitus noise, and tinnitus acceptance, and distress. RESULTS: Exploratory
      factor analysis showed that a single factor solution explained 40% of the
      variance in the scale items. Acceptance and tinnitus habituation (vs.
      sensitization) subscale scores were highly negatively correlated with each other.
      CONCLUSION: Tinnitus acceptance and tinnitus habituation may describe related
      cognitive and perceptual/behavioral aspects of tinnitus adaptation. That is in
      this study, tinnitus-habituation items tapped perceptual awareness and behavioral
      responses to tinnitus, whereas tinnitus acceptance items tapped cognitive
      responses to the noise (i.e. lack of need to respond to the noise).

PMID- 25773108
TI  - Vestibular dysfunction in adolescents and young adults after kidney transplant.
AB  - INTRODUCTION: Chronic kidney disease is a slowly progressive disease that causes
      irreversible loss of renal function and is considered a public health problem
      worldwide. OBJECTIVE: To evaluate the vestibular behavior in patients with
      chronic kidney disease undergoing renal transplantation. METHODS: A retrospective
      cross-sectional study was performed. Thirty patients were evaluated, 33.3% female
      and 66.7% male (mean age 16.9 (+/- 3.6) years old). Patients underwent the
      following procedures: anamnesis, ENT (ear, nose, and throat) evaluation and
      vestibular evaluation. RESULTS: The patients reported dizziness when they were on
      dialysis. 50% the patients showed an abnormality in the vestibular test, which
      occurred in the caloric test. The abnormality was more prevalent in the
      peripheral vestibular system and there was a predominance of deficit peripheral
      vestibular disorders. CONCLUSION: The dizziness was the most significant symptom
      for the vestibular test in correlation with neurotological symptoms. Alteration
      in the vestibular exam occurred in the caloric test, there was a prevalence of
      alterations for the peripheral vestibular system with a predominance of deficit
      vestibular dysfunction. We emphasize the need to show professionals involved in
      patients with chronic kidney disease, those undergoing renal transplant and
      dialitic treatment the importance of prevention and early identification of
      otoneurological involvement.

PMID- 25773109
TI  - Vestibular findings in autosomal recessive ataxia.
AB  - OBJECTIVE: This study aims to examine vestibular disorders in patients with
      recessive spinocerebellar ataxia. DESIGN: A retrospective cross-sectional study
      was conducted. The patients underwent the following procedures: case history, ENT
      and vestibular evaluations. STUDY SAMPLE: The tests were performed in 19 patients
      ranging from 6 to 63 years of age (mean age of 36.7). RESULTS: Clinically, the
      patients commonly had symptoms of dizziness (57.8%), lack of coordination of
      movement with imbalance when walking (52.6%), and headaches (42.1%). In
      vestibular testing, alterations were predominantly evident under caloric testing
      (73.5%), rotational chair testing, and testing for gaze and optokinetic nystagmus
      (36.8%). The presence of alterations occurred under examination in 89.5% of these
      patients, 100% occurred in subjects with Friedreich's ataxia and 84.6% for
      subjects with indeterminate recessive spinocerebellar ataxia, with the majority
      occurring in those with central vestibular dysfunction, 57.9% of the
      examinations. CONCLUSION: The most evident neurotological symptoms were
      dizziness, lack of coordination of movement, and imbalance when walking.
      Alterations in vestibular examinations occurred in 89.5% of patients, mostly in
      the caloric test, with a predominance of deficient central vestibular system
      dysfunction. This underscores the importance of the contribution of
      topodiagnostic labyrinthine evaluations for neurodegenerative diseases.

PMID- 25773110
TI  - Stapedotomy in a residency training program.
AB  - INTRODUCTION: The major objective of a stapedotomy is the restoration of hearing.
      In training centers, the hearing results obtained by resident physicians are
      lower than those achieved by more experienced surgeons. An analysis of the
      surgical results obtained by resident physicians is essential to identification
      of the deficiencies in the learning process. OBJECTIVE: To analyze the
      postoperative hearing results obtained by otosclerosis patients who underwent
      stapedotomy performed by surgeons in a residency program. METHODS: The pre- and
      postoperative audiometric results were evaluated in a retrospective study of 98
      otosclerosis patients who underwent stapedotomy from January 2000 to December
      2010. RESULTS: The distribution of patients according to the postoperative
      results was as follows: 68.4% of the patients achieved a postoperative gap of
      less than or equal to 10 dB, and 91.8% of the patients achieved a postoperative
      gap of less than or equal to 20 dB. Three (3.1%) patients had profound
      sensorineural hearing loss after the procedure. CONCLUSIONS: An improvement in
      surgical outcomes of doctors in training is essential for the continuation of
      training for stapes surgery during medical residency.

PMID- 25773111
TI  - The mismatch negativity test in ears with and without tinnitus-a path to the
      objectification of tinnitus.
AB  - INTRODUCTION: The mismatch negativity (MMN) test evaluates neural responses to
      unexpected sounds, providing objective data on the neural plasticity of the
      auditory system. OBJECTIVES: In this study, we assessed whether the MMN test
      could identify failure of neural habituation of the auditory pathway in patients
      with severe tinnitus. MATERIALS AND METHODS: Patients with normal hearing were
      compared to tinnitus patients, via the MMN test. The Tinnitus Handicap Inventory
      (THI) and a visual analog scale (VAS) were used to evaluate tinnitus-derived
      annoyance. The Hospital Anxiety and Depression (HAD) scale was used to assess
      anxiety and depression. RESULTS: The average MMN amplitudes in the tinnitus group
      were -0.88 uV in the right ear (RE), and -1.13 uV in the left ear (LE), while in
      control group the corresponding amplitudes were 1.01 uV and -1.19 uV. Mean
      latencies in the tinnitus group were 208.34 ms in the RE, and 209.92 ms in the
      LE, while in the control group the corresponding latencies were 217.38 ms and
      215.69 ms. The differences in mean latencies between the groups were
      statistically significant. CONCLUSION: The MMN test may be useful for evaluating
      the habituation process of the central auditory pathways in tinnitus patients.

PMID- 25773112
TI  - One-year prevalence and risk factors of tinnitus in older individuals with
      otological problems.
AB  - OBJECTIVE: The present study was carried out to estimate one year prevalence and
      risk factors of tinnitus in the older individuals (60 years and above) who
      reported with the ear and/or hearing related complaint to All India Institute of
      Speech and hearing, Mysore. METHODS: The case files of those who visited the
      institute during the above said period were reviewed retrospectively. RESULTS:
      The results of the study revealed that the prevalence of tinnitus was 16.81%. It
      was also found that 60.9% of the individuals with tinnitus were males. Further,
      97.5% of the individuals with tinnitus had hearing loss. In addition, 28.53% of
      the individuals with tinnitus had moderate degree of hearing loss followed by
      moderately severe degree of hearing loss. Most of these individuals had
      sensorineural impairment. CONCLUSION: It can be concluded that prevalence of
      tinnitus is quite high in the older individuals with otological problems. The
      hearing loss, gender, giddiness, headache, hypertension, and diabetes were found
      to be major risk factors.

PMID- 25773113
TI  - Characterisitics and maskability of self-reported tinnitus in adult Nigerians.
AB  - BACKGROUND: Tinnitus or noise perception with no identifiable acoustic origin is
      a perplexing symptom to sufferers as well as to otolaryngologists saddled with
      managing such patients. With most studies from the continent focusing on
      etiologies and clinical types, there is paucity of information on psychoacoustic
      properties of tinnitus among Africans. SETTING: Tertiary care otolaryngology
      clinics in Abuja. OBJECTIVE: To determine characteristics and maskability of
      tinnitus seen in adult Nigerians who self-report tinnitus as the main presenting
      symptom. METHODS: A prospective study involving 100 adult Nigerians seen at two
      specialist Otorhinolaryngology clinics in Abuja - National Hospital Abuja and CSR
      Otologics Specialist Clinics, Abuja between January 2008 and June 2014. Clinical
      and audiological history and findings were captured in the study protocol.
      Participants were then assessed to determine Tinnitus pitch match, loudness
      match, mask ability and minimum masking level as well as residual inhibition.
      RESULTS: 100 participants aged 24 - 58 years were assessed. Male to female ratio
      was 1:1.4. Tinnitus was sudden in onset in 24%, and gradual in 76%, involved the
      right ear in 32%, left ear in 38% and both ears in 30%. 48% of participants have
      other symptoms apart from tinnitus, and 32% were on other medications known to
      induce tinnitus. 16% of participants gave history of exposure to significant loud
      sound. Only 16% of participants have significant otoscopic findings. Tinnitus
      abated with carotid pressure in 64%, with extra ocular muscle movement in 16%,
      with teeth clenching in 32%, with neck movement in 28%, and with movement of arms
      or legs in 8%. The mean difference in hearing threshold of ear with and without
      tinnitus was 12.09 dB HL. Tinnitus pitch match was 4 KHz in 44%, 3 KHz in 24%,
      and 2 KHz in 32%, while mean tinnitus loudness match was 41.24 dB SL. Tinnitus
      was maskable in 88% of subjects, with a residual inhibition of 2 to 76 seconds.
      CONCLUSION: Majority of adult Nigerians that self-report tinnitus have maskable
      tinnitus, and this should be considered when considering hearing augmentation for
      those with associated impaired hearing.

PMID- 25773114
TI  - [Does treatment of patients with chronic back pain and proven Modic type 1
      alterations using vertebroplasty make sense?].

PMID- 25773115
TI  - Effect of feeding Aspergillus awamori and canola seed on the growth performance
      and muscle fatty acid profile in broiler chicken.
AB  - The aim of this study was to examine effects of dietary supplementation with
      Aspergillus awamori and feeding canola seed on the growth and fatty acid profile
      in broilers. Twenty-eight chicks (15 days old) were assigned to the following
      groups: (1) control, fed a basal diet; (2) awamori, fed the basal diet
      supplemented with 0.05% A. awamori; (3) canola, fed a diet containing 5% canola
      seed; and (4) canola + awamori, fed the canola diet supplemented with A. awamori
      (seven birds/group). Body weight gain was increased by A. awamori but not
      influenced by canola seed. Breast muscle weight was increased in either awamori
      or canola groups. Although plasma triglyceride and cholesterol were decreased by
      feeding A. awamori or canola seed, fat content in the breast muscle were
      increased, accompanied by decrease in saturated fatty acids and increase in
      unsaturated fatty acids. Moreover, decreased thiobarbituric acid reactive
      substance and increased alpha-tocopherol content in the breast muscle was
      observed in all experimental groups. In conclusion, these results suggested that
      feeding canola seed and A. awamori might improve growth performance, and modified
      muscle fatty acid profile and alpha-tocopherol content, suggesting that they may
      improve meat quality. 

PMID- 25773116
TI  - Diffusion-influenced reactions in a hollow nano-reactor with a circular hole.
AB  - Hollow nanostructures are paid increasing attention in many nanotechnology
      related communities in view of their numerous applications in chemistry and
      biotechnology, e.g. as smart nanoreactors or drug-delivery systems. In this paper
      we consider irreversible, diffusion-influenced reactions occurring within a
      hollow spherical cavity endowed with a circular hole on its surface. Importantly,
      our model is not limited to small sizes of the aperture. In our scheme, reactants
      can freely diffuse inside and outside the cavity through the hole, and react at a
      spherical boundary of given size encapsulated in the chamber and endowed with a
      given intrinsic rate constant. We work out the solution of the above problem,
      enabling one to compute the reaction rate constant to any desired accuracy.
      Remarkably, we show that, in the case of narrow holes, the rate constant is
      extremely well-approximated by a simple formula that can be derived on the basis
      of simple physical arguments and that can be readily employed to analyze
      experimental data. 

PMID- 25773117
TI  - MicroRNA responses to environmental liver carcinogens: Biological and clinical
      significance.
AB  - A large number of biological, chemical, and dietary factors have been implicated
      in the development of liver cancer. These involve complex and protracted
      interactions between genetic, epigenetic, and environmental factors. The survival
      rate for patients diagnosed with late-stage liver cancer is currently low due to
      the aggressive nature of the disease and resistance to therapy. An increasing
      body of evidence has offered support for the crucial role of non-coding microRNA
      (miRNA) in directing hepatic responses to environmental risk factors for liver
      cancer. In this review we focus on miRNA responses to environmental liver cancer
      risk factors and their potential biological and clinical significance. 

PMID- 25773118
TI  - Cervical cancer: Biomarkers for diagnosis and treatment.
AB  - Cervical cancer is a major gynecological cancer which involves uncontrolled cell
      division and tissue invasiveness of the female uterine cervix. With the
      availability of new technologies researchers have increased their efforts to
      develop novel biomarkers for early diagnosis, and evaluation and monitoring of
      therapeutic treatments. This approach will help in the development of early
      diagnosis and in increasing treatment efficacy with decreased recurrence. The
      present review explains the currently available biomarkers for cervical cancer
      diagnosis and prognosis. Apart from the currently available biomarkers the review
      also explains strategies for the development of biomarkers based on cellular and
      molecular approaches such as DNA, protein and other metabolic markers with
      suitable clinical examples. The investigations of specific proteins, enzymes and
      metabolites will establish more useful biomarkers for accurate detection and
      management of gynecological cancers especially cervical cancer. 

PMID- 25773120
TI  - Deconstructing persecution and betrayal in the discourse of Anders Behring
      Breivik: A preliminary essay.
AB  - On 22 July 2011, a 32-year-old Norwegian launched two planned murderous rampages
      claiming the lives of 77 victims. Shortly before his attacks, Anders Behring
      Breivik uploaded to the internet a self-styled compendium written in English in
      which he explained the motivation for his attacks. By deconstructing this text
      and the documentation contained in the first [court-ordered] psychiatric
      evaluation of Breivik, we can undertake to analyse his sense of persecution. In
      pursing this analysis, we start with Breivik's description of his personal
      concept of contemporary European history and politics, and then proceed to the
      autobiographical and phantasmic aspects of his discourse. The analysis reveals
      the transformation of love into hate, the original persecutor, the installation
      of a projection mechanism, notions of betrayal and their subsequent development
      into an ideology. With Breivik's conceptions thus revealed, we conclude by
      comparing different psychoanalytic hypotheses which deepen or challenge the
      Freudian thesis of a defence against a feeling of homosexual love in persecution,
      and which to the contrary favour the importance of the relationship with the
      mother, anal sadism or the 'narcissistic rage' behind the genesis of these ideas.
      We leave open the question of whether there is a constant relationship between
      feelings of persecution and the tendency to commit criminal acts.

PMID- 25773121
TI  - Comparison of Munsell((r)) color chart assessments with primary schoolchildren's
      self-reported skin color.
AB  - BACKGROUND: Skin color is related to human health outcomes, including the risks
      of skin cancer and vitamin D insufficiency. Self-perceptions of skin color may
      influence health behaviours, including the adoption of practices protective
      against harmful solar ultraviolet radiation levels. Misperception of personal
      risk may have negative health implications. The aim of this study is to determine
      whether Munsell((r)) color chart assessments align with child self-reported skin
      color. METHODS: Two-trained investigators, with assessed color acuity, visually
      classified student inner upper arm constitutive skin color. The Munsell((r))
      classifications obtained were converted to Individual Typology Angle (ITA) values
      and respective Del Bino skin color categories after spectrocolorimeter
      measurements based on published values/data. As part of a written questionnaire
      on sun protection knowledge, attitudes, and behaviours, self-completed in class
      time, students classified their end of winter skin color. Student self-reports
      were compared with the ITA-based Del Bino classifications. A total of 477 New
      Zealand primary students attending 27 randomly selected schools from five
      geographic regions. The main measures were self-reported skin color and visually
      observed skin color. RESULTS: A monotonic association was observed between the
      distribution of spectrophotometer ITA scores obtained for Munsell((r)) tiles and
      child self-reports of skin color, providing some evidence for the validity of
      self-report among New Zealand primary school children, although the lighter
      colored ITA defined groups were most numerous in this study sample. Statistically
      significant differences in ITA scores were found by ethnicity, self-reported skin
      color, and geographic residence (P < 0.001). Certain Munsell((r)) color tiles
      were frequently selected as providing a best match to skin color. CONCLUSION:
      Assessment using Munsell((r)) color charts was simple, inexpensive, and practical
      for field use and acceptable to children. The results suggest that this method
      may prove useful for making comparisons with other studies using visual tools to
      assess skin color. Alignment between the ITA distribution derived from the
      Munsell((r)) assessment and child skin color self-reports could probably be
      improved, particularly with the addition of another 'light'/'white' color
      category in the self-report instrument.

PMID- 25773122
TI  - A bispecific antibody directly induces lymphoma cell death by simultaneously
      targeting CD20 and HLA-DR.
AB  - PURPOSE: Both CD20 and HLA-DR antigens are highly expressed on a variety of B
      cell lymphomas and are therapeutic targets in antibody-based lymphoma therapy.
      The aim of this study was to evaluate the anti-tumor effect of a bispecific
      antibody CD20-HLA-DR DVD-Ig on B-cell lymphoma. METHODS: The gene for bispecific
      antibody CD20-HLA-DR DVD-Ig was constructed and expressed in FreeStyleTM293-F
      cells, followed by purification. Their functions were characterized for binding
      to CD20 and HLA-DR and for cytotoxicity against B-cell lymphoma. RESULTS: The
      bispecific antibody CD20-HLA-DR DVD-Ig was engineered using the DNA fragments for
      the anti-CD20 rituximab and anti-HLA-DR hL243gamma1. The CD20-HLA-DR DVD-Ig bound
      simultaneously to both CD20 and HLA-DR, induced potent complement-dependent
      cytotoxicity (CDC) and antibody-dependent cellular cytotoxicity (ADCC) against B
      cell lymphoma, and elicited homotypic adhesion and actin reorganization.
      Treatment of a mixture of human whole blood and Raji cells with CD20-HLA-DR DVD
      Ig effectively depleted Raji cells and had a little toxicity against normal B
      cells. CONCLUSION: Our data indicated that targeting both CD20 and HLA-DR was an
      effective way against NHL, suggesting that CD20-HLA-DR DVD-Ig may be a promising
      therapeutic agent for B-cell lymphoma.

PMID- 25773123
TI  - Evaluation of chemotherapeutics in a three-dimensional breast cancer model.
AB  - PURPOSE: Utilization of miniaturized three-dimensional (3D) cell culture-based
      assays enables investigation into the anticancer activity of drug candidates and
      further elucidation of the anticancer profile of standard-of-care
      chemotherapeutic agents against tumor cells. Drug discovery assays established
      using 3D cell culture, which better recapitulate the tumor microenvironment, may
      more accurately reflect the antitumor activity of compounds. METHODS: Several
      standard-of-care anticancer drugs, epirubicin, paclitaxel and vinorelbine, were
      evaluated against a panel of breast cancer cell lines grown in a 3D cell culture
      microenvironment in the presence of extracellular matrix. A comparison of this
      antitumor activity in 3D conditions was made with that observed in traditional
      two-dimensional (2D) monolayer conditions. RESULTS: Examination of the above
      mentioned drugs against breast tumor cells cultured in 3D conditions demonstrated
      significantly altered potency and efficacy in comparison with cells propagated in
      a 2D monolayer system. The differences observed were cell line-dependent and drug
      specific; the triple-negative cell line MDA-MB-231 and the endocrine receptor
      positive cell line MCF-7 consistently displayed resistance to therapeutics with
      distinct modes of action (i.e., topoisomerase II and microtubules) in 3D cell
      culture in comparison with ErbB2 receptor-positive BT-474 cells. CONCLUSION: The
      data presented herein demonstrates the cellular viability and physical changes
      observed within the 3D spheroid following exposure to drug, which is not always
      reflected in 2D cell culture models.

PMID- 25773124
TI  - Sp1-mediated transcriptional regulation of MALAT1 plays a critical role in tumor.
AB  - BACKGROUND: MALAT1 was discovered as a prognostic marker for lung cancer
      metastasis and has been found upregulated in many types of tumor, but its
      transcriptional regulation mechanism in tumors remains unclear. METHODS: A
      deletion analysis of MALAT1 promoter region was performed to find the cis
      elements that were critical for the transcriptional activation of MALAT1 gene.
      Reporter gene assays were employed to analyze the effect of Sp1 on the promoter
      activity of MALAT1 gene. The binding activity of Sp1 with the promoter of MALAT1
      gene was examined by EMSA and ChIP assay. Effects of Sp1 on regulation of MALAT1
      were analyzed by RNA interference in vitro and in vivo mouse model. RESULTS: By
      means of luciferase assay, Sp1 was found to activate the promoter of the human
      MALAT1 gene. The binding of Sp1 to this region was also detected by
      electrophoretic mobility shift and chromatin immunoprecipitation assays. Sp1
      knockdown also decreased the MALAT1 and inhibited A549 lung cancer cells' growth
      and invasion in vitro. Furthermore, knockdown of Sp1 also mimicked the inhibition
      of MALAT1 in A549 lung cancer cells' growth and metastasis in vivo. CONCLUSIONS:
      Taken together, our data suggest that upregulation of MALAT1 was mediated by the
      transcription factor Sp1 in A549 lung cancer cells, and Sp1 could be therapeutic
      target for cancer.

PMID- 25773125
TI  - Immunohistochemical expression of endoglin offers a reliable estimation of bone
      marrow neoangiogenesis in multiple myeloma.
AB  - PURPOSE: The aim of the present study was to evaluate CD105 tissue marker in the
      bone marrow (BM) of multiple myeloma (MM) patients. CD105 was evaluated using
      immunohistochemical method. An effort was made to correlate this marker with BM
      microvascular density (MVD) along with other known markers of angiogenesis in
      order to evaluate its clinical significance. METHODS: BM MVD was estimated by
      CD31. CD105 in BM was estimated by immunohistochemical method in 54 newly
      diagnosed patients with MM. Circulating levels of known angiogenic factors such
      as basic fibroblast growth factor (b-FGF) and soluble CD105 (sCD105) were
      measured by ELISA in the same group of patients. All these factors were also
      measured in 20 age- and sex-matched healthy controls. RESULTS: We found that
      CD105 MVD, along with the expected CD31 MVD, and serum levels of sCD105 and bFGF
      were increased, also in parallel with disease stage, and all were decreased after
      effective treatment. Moreover, CD105 MVD correlated with all the aforementioned
      markers of angiogenesis. CONCLUSIONS: Our results indicated that CD105 MVD is
      following the behavior of CD31 MVD in MM, suggesting being a valid marker of BM
      neoangiogenesis in MM. Its prognostic impact remains to be proven.

PMID- 25773126
TI  - A retrospective review of diagnosis and treatment modalities of neuroendocrine
      tumors (excluding primary lung cancer) in 10 oncological institutions of the East
      German Study Group of Hematology and Oncology (OSHO), 2010-2012.
AB  - RATIONALE: There is a paucity of data on the incidence of neuroendocrine tumors
      (NET) outside pulmonary primaries and on treatment modalities applied to patients
      with NET in clinical practice. Only very little therapeutic progress has been
      made with respect to response and overall survival, particularly among patients
      with poorly differentiated, WHO grade 3 neuroendocrine carcinomas (G3-NEC). We
      sought to document the incidence and treatment modalities in patients with
      NET/NEC within a period of 2 years. METHODS: We conducted a retrospective data
      analysis using a simple documentation file to be completed in written form or
      electronically, including localization, WHO grading, treatment modalities, and
      specific therapeutic regimens applied. Primary lung cancer was excluded. The time
      period to be covered was 2010 through 2012. Individual patient data such as names
      or age were not documented, so that no ethics committee approval was required.
      RESULTS: Ten different hospital- or practice-based institutions contributed their
      data. One to 35 patients were documented per institution, summing up to 149
      patients with 154 tumor localizations. Midgut (n = 46), foregut (n = 42), hindgut
      (n = 17), lung (n = 9), bladder (n = 8), unknown primary (n = 11), and other
      including prostate and liver (n = 21) were documented as tumor sites.
      Histological gradings were G1 (n = 71), G2 (n = 27), G3 (n = 34),
      undifferentiated "G4" (n = 4), and not specified (n = 13). Treatment modalities
      were surgical resection (n = 102), chemotherapy (n = 49), somatostatin analogs (n
      = 39), radiotherapy (n = 22), receptor-directed radionuclide therapy (n = 12),
      and systemic tyrosine kinase inhibition (n = 5). Chemotherapy was given to
      patients not only with G3-NEC (n = 31), but also with G2 (n = 12) and G1 NET (n =
      7). Somatostatin analogs as well as receptor-directed radionuclides were applied
      to patients throughout all gradings. CONCLUSIONS: NET and NEC are not very rare
      tumor entities, but are diagnosed with very different frequencies, possibly
      depending upon the alertness of pathologists and clinicians. Chemotherapy,
      receptor-directed radionuclide application, and somatostatin analog therapy are
      applied without a clear correlation to different histologic gradings. Diagnostic
      and therapeutic progress in the field of NETs/carcinomas is urgently needed.

PMID- 25773127
TI  - The predictive accuracy of intertemporal-choice models.
AB  - How do people choose between a smaller reward available sooner and a larger
      reward available later? Past research has evaluated models of intertemporal
      choice by measuring goodness of fit or identifying which decision-making
      anomalies they can accommodate. An alternative criterion for model quality, which
      is partly antithetical to these standard criteria, is predictive accuracy. We
      used cross-validation to examine how well 10 models of intertemporal choice could
      predict behaviour in a 100-trial binary-decision task. Many models achieved the
      apparent ceiling of 85% accuracy, even with smaller training sets. When noise was
      added to the training set, however, a simple logistic-regression model we call
      the difference model performed particularly well. In many situations, between
      model differences in predictive accuracy may be small, contrary to long-standing
      controversy over the modelling question in research on intertemporal choice, but
      the simplicity and robustness of the difference model recommend it to future use.

PMID- 25773128
TI  - Mesenchymal tumors of adult kidney.
AB  - Mesenchymal tumors of the kidney, although infrequently encountered, constitute a
      wide spectrum of lesions. The relative rarity of these tumors means that in some
      instances criteria to differentiate between benign and malignancy are currently
      incompletely defined. More recently a variety of novel stromal tumors have been
      characterized, with hemangioblastoma and myopericytoma being notable examples.
      The identification of a subset of spindle cell tumors as synovial sarcoma, on the
      basis of the presence of a characteristic genetic translocation, has facilitated
      the correct classification of a number of tumors previously labeled as
      fibrosarcoma, malignant fibrous histiocytoma, or more recently cystic embryonal
      sarcoma. In this review, we have detailed the spectrum of both benign and
      malignant stromal tumors of the adult kidney, described the gross and microscopic
      features, with an emphasis on immunoexpression and the differential diagnosis of
      each tumor type. 

PMID- 25773129
TI  - Beyond technology acceptance to effective technology use: a parsimonious and
      actionable model.
AB  - OBJECTIVE: To develop and test a parsimonious and actionable model of effective
      technology use (ETU). DESIGN: Cross-sectional survey of primary care providers (n
      = 53) in a large integrated health care organization that recently implemented
      new medication reconciliation technology. METHODS: Surveys assessed 5 technology
      related perceptions (compatibility with work values, implementation climate,
      compatibility with work processes, perceived usefulness, and ease of use) and 1
      outcome variable, ETU. ETU was measured as both consistency and quality of
      technology use. RESULTS: Compatibility with work values and implementation
      climate were found to have differential effects on consistency and quality of
      use. When implementation climate was strong, consistency of technology use was
      high. However, quality of technology use was high only when implementation
      climate was strong and values compatibility was high. This is an important
      finding and highlights the importance of users' workplace values as a key
      determinant of quality of use. CONCLUSIONS: To extend our effectiveness in
      implementing new health care information technology, we need parsimonious models
      that include actionable determinants of ETU and account for the differential
      effects of these determinants on the multiple dimensions of ETU.

PMID- 25773130
TI  - A web-based personally controlled health management system increases sexually
      transmitted infection screening rates in young people: a randomized controlled
      trial.
AB  - OBJECTIVE: To determine if a web-based personally controlled health management
      system (PCHMS) could increase the uptake of sexually transmitted infections (STI)
      screening among a young university population. METHODS: A non-blinded parallel
      group randomized controlled trial was conducted. Participants aged 18-29 years
      were recruited from a university environment between April and August 2013, and
      randomized 1:1 to either the intervention group (immediate online PCHMS access)
      or control group (no PCHMS access). The study outcome was self-reported STI
      testing, measured by an online follow-up survey in October 2013. RESULTS: Of the
      369 participants allocated to the PCHMS, 150 completed the follow-up survey, and
      of the 378 in the control group, 225 completed the follow-up survey. The
      proportion of the PCHMS group who underwent an STI test during the study period
      was 15.3% (23/150) compared with 7.6% (17/225) in the control group (P = .017).
      The difference in STI testing rates within the subgroup of sexually active
      participants (20.4% (23/113) of the PCHMS group compared with 9.6% (15/157) of
      the control group) was significantly higher (P = .027) than among non-sexually
      active participants. DISCUSSION: Access to the PCHMS was associated with a
      significant increase in participants undergoing STI testing. This is also the
      first study to demonstrate efficacy of a PCHMS targeting a health concern where
      susceptibility is generally perceived as low and the majority of infections are
      asymptomatic. CONCLUSION: PCHMS interventions may provide an effective means of
      increasing the demand for STI testing which, combined with increased
      opportunistic testing by clinicians, could reduce the high and sustained rates of
      STIs in young people.

PMID- 25773131
TI  - Impact of protecting ligands on surface structure and antibacterial activity of
      silver nanoparticles.
AB  - Silver nanoparticles (Ag NPs) have attracted much attention in the past decade
      because of their unique physicochemical properties and notable antibacterial
      activities. In particular, thiol-protected Ag NPs have come to the forefront of
      metal nanoparticle studies, as they have been shown to possess high stability and
      interesting structure-property relationships. However, a clear correlation
      between thiol-protecting ligands, the resulting Ag NP surface structure, and
      their antibacterial properties has yet to be determined. Here, a multielement (Ag
      and S), multi-edge (Ag K-edge, Ag L3-edge, S K-edge) X-ray absorption
      spectroscopy (XAS) methodology was used to identify the structure and composition
      of Ag NPs protected with cysteine. XAS characterization was carried out on
      similar-sized Ag NPs protected with poly(vinylpyrrolidone) (PVP), in order to
      provide a valid comparison of the ligand effect on surface structure. The PVP-Ag
      NPs showed a metallic Ag surface and composition, consistent with metal NPs
      protected by weak protecting ligands. On the other hand, the Cys-Ag NPs exhibited
      a distinct surface shell of silver sulfide, which is remarkably different than
      previously studied Cys-Ag NPs. The minimum inhibitory concentration (MIC) of both
      types of Ag NPs against Gram-positive (+) and Gram-negative (-) bacteria were
      tested, including Staphylococcus aureus (+), Escherichia coli (-), and
      Pseudomonas aeruginosa (-). It was found that the MICs of the Cys-Ag NPs were
      significantly lower than the PVP-Ag NPs for each bacteria, implicating the
      influence of the sulfidized surface structure. Overall, this work shows the
      effect of ligand on the surface structure of Ag NPs, as well as the importance of
      surface structure in controlling antibacterial activity. 

PMID- 25773132
TI  - The diet of free-roaming Australian Central Bearded Dragons (Pogona vitticeps).
AB  - The central bearded dragon (Pogona vitticeps) is one of the most popular pet
      lizards. However, little is known regarding their nutrient requirement, or their
      natural diet. Therefore, the stomach contents of 14 free-roaming P. vitticeps
      were determined by flushing. These stomach contents were described taxonomically,
      and analyzed for crude protein content as well as fatty acid content and
      composition. Most of the dry matter intake was in the form of animal material
      (61%) stemming from nine arthropod orders. The most abundant were alates of the
      termite Drepanotermes sp., accounting for 95% of the total number of prey items
      and more than half of the total dry matter (DM) intake. Plant material
      contributed 16% of the total DM intake. The diets were high in crude protein (41
      50% DM) and the total fatty acid content was 14-27% of the DM intake. The main
      fatty acid was C18:1n9c (51-56% of total fatty acids), and polyunsaturated fatty
      acids (n3 and n6) comprised 6-8% of the total fat intake. Our data suggest that
      P. vitticeps is an opportunistic predator, which exploits the seasonal
      availability of prey. Based on our data and other studies, a diet consisting of
      several insect species, supplemented with leafy vegetables, rich in n3 FA's,
      would best resemble the expected natural diet of P. vitticeps.

PMID- 25773133
TI  - Short- and Long-Term Outcomes of Student Field Research Experiences in Special
      Populations.
AB  - Global health education and training of biomedical students in international and
      minority health research is expending through U.S. academic institutions. This
      study addresses the short- and long-term outcomes of an NCI-funded R25 short-term
      summer field research training program. This program is designed for MPH and
      Ph.D. students in cancer epidemiology and related disciplines, in international
      and minority settings (special populations) in a recent 7-year period. Positive
      short-term outcome of 73 students was measured as publishing a manuscript from
      the field research data and having a job in special populations. Positive long
      term outcome was measured as having a post-doc position, being in a doctoral
      program, and/or employment in special populations at least 3 years from finishing
      the program. Significant factors associated with both short- and long-term
      success included resourcefulness of the student and compatibility of
      personalities and interests between the student and the on-campus and off-campus
      mentors. Short-term-success of students who conducted international filed
      research was associated with visits of the on-campus mentor to the field site.
      Short-term success was also associated with extent of mentorship in the field
      site and with long-term success. Future studies should investigate how field
      research sites could enhance careers of students, appropriateness of the sites
      for specific training competencies, and how to maximize the learning experience
      of students in international and minority research sites.

PMID- 25773134
TI  - Patient-Centered Cancer Care Programs in Italy: Benchmarking Global Patient
      Education Initiatives.
AB  - In Italy, educational programs for cancer patients are currently provided by the
      national government, scientific societies, and patient advocate organizations.
      Several gaps limit their effectiveness, including the lack of coordinated
      efforts, poor involvement of patient feedback in the planning of programs, as
      well as a lack of resources on innovative cancer-related topics. This process is
      parallel to a strong shift in the attitude of patients towards health in general
      and taking charge of their own health conditions in particular. The National
      Cancer Institute in the USA and the Organization of European Cancer Institutes
      encourage comprehensive cancer centers in providing educational programs
      conceived to overcome these gaps. The goal of this paper is to identify and
      describe the key elements necessary to develop a global patient education program
      and provide recommendations for strategies with practical examples for
      implementation in the daily activities of cancer institutes. A multidisciplinary
      committee was established for patient education, including patient
      representatives as equal partners, to define, implement, verify, and evaluate the
      fundamental steps for establishing a comprehensive education program. Six
      essential topics were identified for the program: appropriate communication of
      cancer epidemiology, clinical trial information, new therapeutic technologies,
      support in the use of medicines, psycho-oncological interventions, age
      personalized approaches, and training programs for healthcare providers.
      Integration of these topics along with patient feedback is the key to a
      successful model for educational programs. An integrated educational program can
      transform a comprehensive cancer center to an institution that provides research
      and care for and with patients. 

PMID- 25773135
TI  - Education in End-of-Life Care: What Do Experienced Professionals Find Important?
AB  - End-of-life care is an essential element of quality cancer care. Nevertheless, a
      majority of physicians and nurses working at cancer centers feel unprepared for
      this task. As part of a larger survey study, we investigated what suggestions
      experienced physicians and nurses have to improve education/training on end-of
      life care. In an open question, participants were requested to suggest changes to
      the end-of-life curriculum for physicians and nurses. Answers to this question
      were content analyzed using the qualitative data analysis software MAXQDA.
      Physicians and nurses at 10 cancer centers throughout Baden-Wuerttemberg were
      surveyed. From the total 1131 survey participants, 675 (483 nurses, 167
      physicians, 25 unknown) responded to the open question regarding suggestions for
      education/training in end-of-life care. Two main categories were inductively
      developed: (1) format (i.e., structure and method of teaching) and (2) content
      (i.e., knowledge and know-how required for care of the dying). Regarding format,
      both professional groups most often wished for more practical experiences with
      dying patients (e.g., internships at hospices). Regarding content, physicians and
      nurses most frequently requested (1) more basic information on palliative care,
      (2) increased skills training in communication, and (3) knowledge of how to
      appropriately care for patients' caregivers. The results of our analysis reflect
      already trained physicians' and nurses' interest in furthering their knowledge
      and skills to care for dying patients. The suggestions of experienced physicians
      and nurses should be integrated into the further development of palliative care
      curricula. 

PMID- 25773136
TI  - A Web-Based Platform for Educating Researchers About Bioethics and Biobanking.
AB  - Participation in biobanking among individuals with familial risk for hereditary
      cancer (IFRs) and underserved/minority populations is vital for biobanking
      research. To address gaps in researcher knowledge regarding ethical concerns of
      these populations, we developed a web-based curriculum. Based on formative
      research and expert panel assessments, a curriculum and website was developed in
      an integrative, systematic manner. Researchers were recruited to evaluate the
      curriculum. Public health graduate students were recruited to pilot test the
      curriculum. All 14 researchers agreed the curriculum was easy to understand,
      adequately addressed the domains, and contained appropriate post-test questions.
      The majority evaluated the dialgoue animations as interesting and valuable.
      Twenty-two graduate students completed the curriculum, and 77 % improved their
      overall test score. A web-based curriculum is an acceptable and effective way to
      provide information to researchers about vulnerable populations' biobanking
      concerns. Future goals are to incorporate the curriculum with larger
      organizations. 

PMID- 25773137
TI  - Studies of minute quantities of natural abundance molecules using 2D
      heteronuclear correlation spectroscopy under 100 kHz MAS.
AB  - Two-dimensional (1)H{(13)C} heteronuclear correlation solid-state NMR spectra of
      naturally abundant solid materials are presented, acquired using the 0.75-mm
      magic angle spinning (MAS) probe at spinning rates up to 100 kHz. In spite of the
      miniscule sample volume (290 nL), high-quality HSQC-type spectra of bulk samples
      as well as surface-bound molecules can be obtained within hours of experimental
      time. The experiments are compared with those carried out at 40 kHz MAS using a
      1.6-mm probe, which offered higher overall sensitivity due to a larger rotor
      volume. The benefits of ultrafast MAS in such experiments include superior
      resolution in (1)H dimension without resorting to (1)H-(1)H homonuclear RF
      decoupling, easy optimization, and applicability to mass-limited samples. The
      HMQC spectra of surface-bound species can be also acquired under 100 kHz MAS,
      although the dephasing of transverse magnetization has significant effect on the
      efficiency transfer under MAS alone.

PMID- 25773138
TI  - Resonance assignments of the myristoylated Y28F/Y67F mutant of the Mason-Pfizer
      monkey virus matrix protein.
AB  - The matrix protein (MA) of the Mason-Pfizer monkey virus (M-PMV) plays a key role
      in the transport and budding of immature retroviral particles from the host cell.
      Natural N-terminal myristoylation of MA is essential for the targeting of the
      particles to the plasma membrane and participates in the interaction of MA with
      membranes phospholipids. The mutation Y28F/Y67F in MA reduces budding and thus
      causes the accumulation of viral particles under the cytoplasmic membrane. To
      investigate the impact of Y28F/Y67F mutation on the structure of MA, we prepared
      this protein in amount and quality suitable for NMR spectroscopy. We report
      backbone, side-chain and myristoyl residue assignments of the Y28F/Y67F mutant of
      the M-PMV matrix protein, which will be used to study the interaction with
      membrane phospholipids and to determine the structure of the mutant matrix
      protein. 

PMID- 25773139
TI  - Effects of Bone Marrow Mononuclear Cells Delivered through a Graft Vessel for
      Patients with Previous Myocardial Infarction and Chronic Heart Failure: An
      Echocardiographic Study of Left Atrium Function.
AB  - OBJECTIVES: The graft of stem cells to treat ischemic cardiomyopathy is popular
      in many clinical trials. The aim of this study was to evaluate the effectiveness
      of isolated coronary artery bypass graft combined with bone marrow mononuclear
      cells (BMMNC) delivered through the graft vessels to improve left atrium (LA)
      function of patients with previous myocardial infarction and chronic heart
      failure using echocardiography. METHODS: Forty-two patients with previous
      myocardial infarction and chronic heart failure were randomly allocated to one of
      the two groups: coronary artery bypass graft (CABG) only (18 in CABG group) or
      CABG with BMMNC transplantation (24 in CABG + BMMNC group). Echocardiographic
      parameters were measured on two-dimensional (2D) imaging, three-dimensional
      imaging, 2D strain, and strain rate imaging, eight parameters were measured
      totally. RESULTS: Postoperative LA global strain (LAGS) versus Preoperative LAGS
      were 24.875 +/- 1.588% versus 14.250 +/- 1.281% (P < 0.05) in CABG + BMMMNC group
      and 17.556 +/- 1.834% versus 13.111 +/- 1.479% (P < 0.05) in CABG group, LVEF was
      49.083 +/- 1.914% versus 36.042 +/- 1.185% (P < 0.05) in CABG + BMMMNC group and
      41.389 +/- 2.210% versus 34.667 +/- 1.369% (P < 0.05) in CABG group, and LA
      volume (LAV) was 15.651 +/- 0.631 mL versus 23.894 +/- 0.831 mL (P < 0.05) in
      CABG + BMMMNC group and 21.429 +/- 0.707 mL versus 22.379 +/- 0.959 mL (P < 0.05)
      in CABG group. LAGS, LVEF, and LAV were significantly improved postoperatively in
      both groups. The degree of the improvement was significantly different between
      the two groups with the CABG + BMMNC group improved more versus the group of CABG
      only (P < 0.05). Postoperative LVEDV and LVESV were significantly improved
      compared with those obtained prior to operation in CABG + BMMNC group (P < 0.05).
      CONCLUSIONS: The improvement of LA function in CABG + BMMNC group is better than
      CABG group. 2D strain imaging is a more sensitive tool to evaluate LA function.

PMID- 25773140
TI  - Investigational drugs under development for the treatment of PTSD.
AB  - INTRODUCTION: Posttraumatic stress disorder (PTSD) is a prevalent, chronic and
      disabling anxiety disorder that may develop following exposure to a traumatic
      event. There is currently no effective pharmacotherapy for PTSD and therefore the
      discovery of novel, evidence-based treatments is particularly important. This
      review of potential novel treatments could act as a catalyst for further drug
      investigation. AREAS COVERED: In this review, the authors discuss the
      heterogeneity of PTSD and why this provides a challenge for discovering effective
      treatments for this disorder. By searching for the neurobiological systems that
      are disrupted in individuals with PTSD and their correlation with different
      symptoms, the authors propose potential pharmacological treatments that could
      target these symptoms. They discuss drugs such as nabilone, d-cycloserine, nor
      BNI, 7,8-dihydroxyflavone and oxytocin (OT) to target systems such as
      cannabinoids, glutamate, opioids, brain-derived neurotrophic factor and the OT
      receptor, respectively. While not conclusive, the authors believe that these
      brain systems include promising targets for drug discovery. Finally, the authors
      review animal studies, proof-of-concept studies and case studies that support our
      proposed treatments. EXPERT OPINION: A mechanism-based approach utilizing
      techniques such as in vivo neuroimaging will allow for the determination of
      treatments. Due to the heterogeneity of the PTSD phenotype, focusing on
      symptomology rather than a categorical diagnosis will allow for more personalized
      treatment. Furthermore, there appears to be a promise in drugs as cognitive
      enhancers, the use of drug cocktails and novel compounds that target specific
      pathways linked to the etiology of PTSD.

PMID- 25773141
TI  - Crystal structure of the Csm1 subunit of the Csm complex and its single-stranded
      DNA-specific nuclease activity.
AB  - The CRISPR-Cas system is the RNA-guided immune defense mechanism in bacteria and
      archaea. Csm1 belongs to the Cas10 family, which is the common signature protein
      of the type III system. Csm1 is the largest subunit of the Csm interference
      complex in the type III-A subtype, which targets foreign DNA or RNA. Here, we
      report crystallographic and biochemical analyses of Thermococcus onnurineus Csm1,
      revealing a five-domain organization and single-stranded DNA (ssDNA)-specific
      nuclease activity associated with the N-terminal HD domain. This domain folds
      into permuted secondary structures in comparison with the HD domain of Cas3 and
      contains all the catalytically important residues. It exhibited both endo- and
      exonuclease activities in an Ni(2+) or Mn(2+)-dependent manner. The narrow width
      of the active-site cleft appears to restrict the substrate specificity to ssDNA
      and thus to prevent Csm1 from cleaving double-stranded chromosomal DNA. These
      data suggest that Csm1 may function in DNA interference by the Csm effector
      complex. 

PMID- 25773142
TI  - Structure and dynamics of the integrin LFA-1 I-domain in the inactive state
      underlie its inside-out/outside-in signaling and allosteric mechanisms.
AB  - Lymphocyte function-associated antigen 1 (LFA-1) is an integrin that transmits
      information in two directions across the plasma membrane of leukocytes, in so
      called outside-in and inside-out signaling mechanisms. To investigate the
      structural basis of these mechanisms, we studied the conformational space of the
      apo I-domain using replica-averaged metadynamics simulations in combination with
      nuclear magnetic resonance chemical shifts. We thus obtained a free energy
      landscape that reveals the existence of three conformational substates of this
      domain. The three substates include conformations similar to existing
      crystallographic structures of the low-affinity I-domain, the inactive I-domain
      with an allosteric antagonist inhibitor bound underneath alpha helix 7, and an
      intermediate affinity state of the I-domain. The multiple substates were
      validated with residual dipolar coupling measurements. These results suggest that
      the presence of three substates in the apo I-domain enables the precise
      regulation of the binding process that is essential for the physiological
      function of LFA-1. 

PMID- 25773143
TI  - Structurally distinct ubiquitin- and sumo-modified PCNA: implications for their
      distinct roles in the DNA damage response.
AB  - Proliferating cell nuclear antigen (PCNA) is a pivotal replication protein, which
      also controls cellular responses to DNA damage. Posttranslational modification of
      PCNA by SUMO and ubiquitin modulate these responses. How the modifiers alter PCNA
      dependent DNA repair and damage tolerance pathways is largely unknown. We used
      hybrid methods to identify atomic models of PCNAK107-Ub and PCNAK164-SUMO
      consistent with small-angle X-ray scattering data of these complexes in solution.
      We show that SUMO and ubiquitin have distinct modes of association to PCNA.
      Ubiquitin adopts discrete docked binding positions. By contrast, SUMO associates
      by simple tethering and adopts extended flexible conformations. These structural
      differences are the result of the opposite electrostatic potentials of SUMO and
      Ub. The unexpected contrast in conformational behavior of Ub-PCNA and SUMO-PCNA
      has implications for interactions with partner proteins, interacting surfaces
      accessibility, and access points for pathway regulation. 

PMID- 25773144
TI  - Dynamic changes during acid-induced activation of influenza hemagglutinin.
AB  - Influenza hemagglutinin (HA) mediates virus attachment to host cells and fusion
      of the viral and endosomal membranes during entry. While high-resolution
      structures are available for the pre-fusion HA ectodomain and the post-fusion HA2
      subunit, the sequence of conformational changes during HA activation has eluded
      structural characterization. Here, we apply hydrogen-deuterium exchange with mass
      spectrometry to examine changes in structural dynamics of the HA ectodomain at
      various stages of activation, and compare the soluble ectodomain with intact HA
      on virions. At pH conditions approaching activation (pH 6.0-5.5) HA exhibits
      increased dynamics at the fusion peptide and neighboring regions, while the
      interface between receptor binding subunits (HA1) becomes stabilized. In contrast
      to many activation models, these data suggest that HA responds to endosomal
      acidification by releasing the fusion peptide prior to HA1 uncaging and the
      spring-loaded refolding of HA2. This staged process may facilitate efficient HA
      mediated fusion. 

PMID- 25773146
TI  - UV sensing using film bulk acoustic resonators based on Au/n-ZnO/piezoelectric
      ZnO/Al structure.
AB  - A new type of ultraviolet (UV) light sensor based on film bulk acoustic wave
      resonator (FBAR) is proposed. The new sensor uses gold and a thin n-type ZnO
      layer deposited on the top of piezoelectric layer of FBAR to form a Schottky
      barrier. The Schottky barrier's capacitance can be changed with UV light,
      resulting in an enhanced shift in the entire FBAR's resonant frequency. The
      fabricated UV sensor has a 50 nm thick n-ZnO semiconductor layer with a carrier
      concentration of ~ 10(17) cm(-3). A large frequency downshift is observed when UV
      light irradiates the FBAR. With 365 nm UV light of intensity 1.7 mW/cm(2), the
      FBAR with n-ZnO/Au Schottky diode has 250 kHz frequency downshift, much larger
      than the 60 kHz frequency downshift in a conventional FBAR without the n-ZnO
      layer. The shift in the new FBAR's resonant frequency is due to the junction
      formed between Au and n-ZnO semiconductor and its properties changes with UV
      light. The experimental results are in agreement with the theoretical analysis
      using an equivalent circuit model of the new FBAR structure.

PMID- 25773145
TI  - Correlation of gene methylation in surgical margin imprints with locoregional
      recurrence in head and neck squamous cell carcinoma.
AB  - BACKGROUND: Securing negative surgical margins is a critical goal for head and
      neck surgery. Local recurrence develops even in some patients who have
      histologically negative surgical margins. Minimal residual tumor cells may lead
      to locoregional recurrence despite clear histologic margins reported at the time
      of resection of head and neck squamous cell carcinoma (HNSCC). To identify
      subclinical residual disease, the authors analyzed deep margin imprint samples
      collected on 1-layer nitrocellulose sheets. METHODS: Bisulfite-treated DNA
      samples from 73 eligible patients were amplified by quantitative methylation
      specific polymerase chain reaction (QMSP) targeting 6 genes (deleted in
      colorectal cancer [DCC], endothelin receptor type B [EDNRB], homeobox protein A9
      [HOXA9], kinesin family member 1A [KIF1A], nidogen-2 [NID2], and N-methyl D
      aspartate receptor subtype 2B [NR2B]). QMSP values were dichotomized as positive
      or negative. Associations between the QMSP status of deep margin samples and
      clinical outcomes were evaluated. RESULTS: Two-gene methylation combinations
      among the genes DCC, EDNRB, and HOXA9 were associated with decreased locoregional
      recurrence-free survival, recurrence-free survival, and overall survival. The
      methylated gene combination of EDNRB and HOXA9 in margin imprints was the most
      powerful predictor of poor locoregional recurrence-free survival (hazard ratio
      [HR], 3.31; 95% confidence interval [CI], 1.30-8.46; P = .012) independent of
      standard histologic factors. In addition, methylation of both EDNRB and HOXA9
      indicated a trend toward reduced recurrence-free survival (HR, 2.74; 95% CI, 0.90
      8.33; P = .075) and reduced OS (HR, 5.78; 95% CI, 0.75-44.7; P = .093) in
      multivariable analysis. CONCLUSIONS: A panel of gene methylation targets in deep
      surgical margin imprints provides a potential predictive marker of postoperative
      locoregional recurrence. Intraoperative use of molecular margin imprint analysis
      may assist surgeons in obtaining rigorously negative surgical margins and improve
      the outcome of head and neck surgery.

PMID- 25773147
TI  - Suppression of murine experimental autoimmune encephalomyelitis development by
      1,25-dihydroxyvitamin D3 with autophagy modulation.
AB  - Multiple sclerosis (MS) has been associated with a history of sub-optimal
      exposure to ultraviolet light, implicating vitamin D3 as a possible protective
      agent. We evaluated whether 1,25(OH)2D3 attenuates the progression of
      experimental autoimmune encephalomyelitis (EAE), and explored its potential
      mechanisms. EAE was induced in C57BL/6 mice via immunization with MOG35-55, and
      some mice received 1,25(OH)2D3. 1,25(OH)2D3 inhibited EAE progression.
      Additionally, 1,25(OH)2D3 reduced inflammation, demyelination, and neuron loss in
      the spinal cord. The protective effect of 1,25(OH)2D3 was associated with
      significantly elevated expression of Beclin1, increased Bcl-2/Bax ratio, and
      decreased LC3-II accumulation. Thus, 1,25(OH)2D3 may represent a promising new MS
      treatment. 

PMID- 25773148
TI  - Improvement of fatigue in multiple sclerosis by physical exercise is associated
      to modulation of systemic interferon response.
AB  - Mechanisms underlying multiple sclerosis (MS) fatigue and the causes of the
      beneficial effect of exercise on this symptom are not clarified. Our aim was to
      evaluate gene expression profiles in MS patients who improved their fatigue
      status after an exercise program and to compare them with healthy controls (HC).
      Gene expression in whole blood was profiled at baseline in 7 HC and also in 7
      fatigued-MS patients. Patients underwent an exercise program for 6 months, and
      their fatigue status and gene expression profiles were again analyzed. MS
      patients showed a significant activation of genes participating in the systemic
      interferon response in comparison with HC that disappeared at the end of the
      program. Our results provide a biological basis for the observed benefit of
      exercise in MS.

PMID- 25773150
TI  - A possible association between elevated serum levels of brain-specific auto
      antibodies and reduced plasma levels of docosahexaenoic acid in autistic
      children.
AB  - Polyunsaturated fatty acids (PUFAs) are not only essential for energy production,
      but they also exhibit a range of immunomodulatory properties that progress
      through T cell mediated events. Autoimmunity may have a pathogenic role in a
      subgroup of autistic children. This study is the first to investigate the
      relationship between serum levels of anti-myelin basic protein (anti-MBP) brain
      specific auto-antibodies and reduced plasma levels of PUFAs in autistic children.
      Plasma levels of PUFAs (including linoleic, alphalinolenic, arachidonic "AA" and
      docosahexaenoic "DHA" acids) and serum anti-MBP were measured in 80 autistic
      children, aged between 4 and 12 years, and 80 healthy-matched children. Autistic
      patients had significantly lower plasma levels of PUFAs than healthy children. On
      the other hand, omega6/omega3 ratio (AA/DHA) was significantly higher in autistic
      patients than healthy children. Low plasma DHA, AA, linolenic and linoleic acids
      were found in 67.5%, 50%, 40% and 35%, respectively of autistic children. On the
      other hand, 70% of autistic patients had elevated omega6/omega3 ratio. Autistic
      patients with increased serum levels of anti-MBP auto-antibodies (75%) had
      significantly lower plasma DHA (P<0.5) and significantly higher omega6/omega3
      ratio (P<0.5) than patients who were seronegative for these antibodies. In
      conclusions, some autistic children have a significant positive association
      between reduced levels of plasma DHA and increased serum levels of anti-MBP brain
      specific auto-antibodies. However, replication studies of larger samples are
      recommended to validate whether reduced levels of plasma PUFAs are a mere
      association or have a role in the induction of the production of anti-MBP in some
      autistic children. 

PMID- 25773149
TI  - Vitamin D3 administration to MS patients leads to increased serum levels of
      latency activated peptide (LAP) of TGF-beta.
AB  - BACKGROUND: Deficiency of vitamin D is an environmental risk factor for MS.
      Vitamin D has immunomodulatory effects, including promotion of T-cell
      differentiation into T-regulatory cells, which produces regulatory cytokines
      including TGF-beta. Increasing serum vitamin D levels have been associated with
      decreased disease activity in MS patients, but there are only few studies
      concerning the immunological effects of vitamin D supplementation in MS. In this
      study we investigated the effect of weekly supplementation of vitamin D3 or
      placebo on serum levels of multiple cytokines in patients with relapsing
      remitting MS. METHODS: The study was conducted on the patient cohort of the
      Finnish Vitamin D study. All patients were using IFN-beta-1b and were randomized
      to add-on treatment with either cholecalciferol 20,000 IU/week or placebo.
      Concentrations of LAP (TGF-beta), INF-gamma, IL-17A, IL-2, IL-10, IL-9, IL-22, IL
      6, IL-13, IL-4, IL-5, IL-1beta and TNF-alpha were determined at screening and at
      12 months using commercial fluorescent bead immunoassay kits. RESULTS: LAP (TGF
      beta) levels increased significantly in the vitamin D treated group from a mean
      of 47 (SE 11) pg/ml to 55 (SE 14) pg/ml in 12 months (p-value=0.0249). Placebo
      treatment had no significant effect on LAP levels. The levels of the other
      cytokines did not change significantly in either group. CONCLUSIONS: We showed
      increased serum latency activated peptide (LAP) of TGF-beta levels in MS patients
      treated with vitamin D3. The immune regulatory effects of TGF-beta may play a
      role in the improved MRI outcomes that we observed earlier in the vitamin D
      treated group of patients.

PMID- 25773151
TI  - Vitamin D status and effect of interferon-beta1a treatment on MRI activity and
      serum inflammation markers in relapsing-remitting multiple sclerosis.
AB  - To explore if vitamin D modulates interferon-beta1a treatment effects in
      relapsing-remitting multiple sclerosis, we examined relationships between serum
      vitamin D and magnetic resonance imaging (MRI) activity and ten systemic
      inflammation markers in 88 patients, before and during treatment. Odds ratios for
      all MRI parameters were negatively associated with vitamin D levels before
      therapy, but converged to equally low values irrespective of vitamin D status
      during treatment. During therapy, similar alterations of MRI activity and
      inflammation markers were found across patients categorized by mean vitamin D
      values. This suggests that vitamin D status has no major influence on interferon
      beta1a treatment effects. 

PMID- 25773152
TI  - HMGB1 expression patterns during the progression of experimental autoimmune
      encephalomyelitis.
AB  - High mobility group box 1 (HMGB1), a nonhistone chromatin associated protein,
      plays different roles according to the expression pattern such as the amount,
      cell location and sub-cellular location. It has been recently demonstrated that
      the systemic HMGB1 is associated with autoimmune encephalomyelitis. However, the
      dynamic change of HMGB1 expression pattern in spinal cords that may be involved
      in the progression of disease is not fully understood. In this study, the amount,
      cell location and subcellular location of HMGB1 in adult mice spinal cords during
      various stages of experimental autoimmune encephalomyelitis (EAE) are
      investigated. HMGB1 is expressed in the nuclei of spinal cord resident cells such
      as some astrocytes, microglia and a few neurons in normal situation. During EAE
      progression, the total and extracellular HMGB1 in the spinal cord are increased,
      more HMGB1 positive astrocytes and microglia are observed, and the intra-neurons
      HMGB1 in the ventral horn and around the central canal localize majorly in the
      cytoplasm accompanied by the increasing extracellular HMGB1. Blockade of HMGB1 in
      central nervous system (CNS) locally attenuates the severity of EAE
      significantly. Our findings indicate that the HMGB1 expression pattern in the
      spinal cord is associated with the progression of EAE. HMGB1 may be a potential
      target for autoimmune encephalomyelitis (multiple sclerosis in human) therapy. 

PMID- 25773153
TI  - GM-CSF production by CD4+ T cells in MS patients: regulation by regulatory T
      cells and vitamin D.
AB  - BACKGROUND/OBJECTIVE: Data from animal models of MS suggest that GM-CSF(+)CD4(+)T
      cells are pathogenic cells. Therefore, GM-CSF production by CD4(+)T cells of MS
      patients and their susceptibility to regulatory mechanisms were investigated.
      METHODS: Intracellular flowcytometry was performed to determine the GM
      CSF(+)CD4(+)T cell fraction in PBMC and CSF of MS patients and controls. The
      effect of regulatory T cells (Tregs) on GM-CSF production by CD4(+)T cells was
      studied in MS patients using a proliferation-suppression assay. Finally, GM
      CSF(+)CD4(+)T cell fraction and GM-CSF protein levels in supernatant were
      assessed in anti-CD3-stimulated CD4(+)T cell cultures derived from healthy
      controls and MS patients, in the presence or absence of the active vitamin D
      metabolite calcitriol. RESULTS: The GM-CSF(+)CD4(+)T cell fraction in the
      peripheral blood did not differ between controls and MS patients. This T cell
      population could also be detected in the CSF of both subjects with MS as well as
      subjects with another diagnosis. In the CSF, it comprised a significant fraction
      of the T cell population. Upon in vitro stimulation of PBMC with anti-CD3
      antibody, no differences were observed in GM-CSF(+)CD4(+)T cell frequencies. GM
      CSF secretion was susceptible to regulation by Treg and vitamin D. Suppression of
      GM-CSF secretion by vitamin D was reduced in MS patients. CONCLUSIONS: Our study
      showed no elevation in GM-CSF(+)CD4(+)T cell fractions in MS patients compared to
      controls. Furthermore, GM-CSF secretion was prone to regulation by Treg and
      vitamin D, the latter being less effective in MS patients.

PMID- 25773154
TI  - Analysis of apoptosis-related genes in patients with clinically isolated syndrome
      and their association with conversion to multiple sclerosis.
AB  - To analyse whether the expression of apoptotic transcripts is associated with the
      conversion from clinically isolated syndrome (CIS) to multiple sclerosis (MS).
      Eleven candidate transcripts belonging to the death receptor pathway, BCL-2, the
      inflammasome complex and NF-KappaB family were studied in the nonconverting and
      converting CIS patients during the four-year follow-up period. Conversion to MS
      was associated with marked variability in the expression of proapoptotic genes
      that were linked to TGF-B1 gene levels. The predominant expression of
      proapoptotic genes in patients with CIS suggests an increased potential to
      undergo apoptosis with the goal of terminating immune responses and regulating
      immune system homeostasis. 

PMID- 25773156
TI  - Comment on "Dysregulated production of leukemia inhibitory factor in immune cells
      of relapsing remitting multiple sclerosis patients" by Levy et al. J.
      Neuroimmunol. 2015 Jan 15; 278C:85-89.

PMID- 25773157
TI  - A possible role of endogenous central corticotrophin releasing factor in
      lipopolysaccharide induced thymic involution and cell apoptosis: effect of
      peripheral injection of corticotrophin releasing factor.
AB  - The aim of the study was to investigate the role of endogenous peripheral and
      central corticotrophin-releasing factor (CRF) following lipopolysaccharide (LPS)
      challenge on thymic involution and apoptosis. Administration of LPS (100
      MUg/mouse, ip) led to thymic involution, to a decrease of CD4+CD8+ thymocyte
      subset, and to fragmentation of thymic DNA. Pretreatment of LPS challenged mice
      with intracerebroventricular alpha-helical CRF (a CRF antagonist) attenuated the
      effect of LPS however, intraventricular administered alpha-helical CRF failed to
      affect LPS response on thymus. Moreover, the effects of LPS on thymus, examined
      on 1, 7 and 14 days were wholly abrogated by prior administration of
      intraventricular CRF (10 MUg/animal). The plasma corticosterone levels were found
      to be decreased with single dose of peripheral CRF in LPS challenged mice. These
      findings indicate that central endogenous CRF involved in LPS induced thymic
      atrophy. However, peripheral CRF offers protective effect on LPS induced thymic
      involution and cell apoptosis.

PMID- 25773155
TI  - Evidence of different mediators of central inflammation in dysfunctional and
      inflammatory pain--interleukin-8 in fibromyalgia and interleukin-1 beta in
      rheumatoid arthritis.
AB  - The purpose of this study was to relate central inflammation to autonomic
      activity (heart rate variability (HRV)) in patients with rheumatoid arthritis
      (RA) and fibromyalgia (FM). RA patients had reduced parasympathetic activity and
      FM patients had increased sympathetic activity compared to healthy controls.
      Comparisons between RA and FM showed higher cerebrospinal fluid (CSF) interleukin
      (IL)-1beta inversely correlated to parasympathetic activity in RA. The FM
      patients had higher concentrations of CSF IL-8, IL-1Ra, IL-4 and IL-10, but none
      of these cytokines correlated with HRV. In conclusion, we found different
      profiles of central cytokines, i.e., elevated IL-1beta in inflammatory pain (RA)
      and elevated IL-8 in dysfunctional pain (FM). 

PMID- 25773158
TI  - Epitopes of HERV-Wenv induce antigen-specific humoral immunity in multiple
      sclerosis patients.
AB  - To verify the serological response mounted against antigenic peptides from HERV
      Wenv protein, we analyzed 80 multiple sclerosis (MS) serum samples, 27 of which
      were re-analyzed after a 6-month follow-up IFN-beta therapy, and 73 healthy
      controls. Indirect ELISAs were carried out to detect antibodies specific for all
      the synthetic peptides derived from HERV-Wenv. Two antigenic peptides, HERV
      Wenv93-108 (31.25%, p<0.0001) and HERV-Wenv248-262 (15%, p=0.02), were highly
      recognized by MS patients' antibodies when compared to healthy subjects.
      Moreover, antibody titer against these two peptides slightly decreased after six
      months of IFN-beta-based therapy. 

PMID- 25773159
TI  - A case of refractory antilaminin gamma1 pemphigoid successfully treated with
      dexamethasone and mycophenolate mofetil.

PMID- 25773160
TI  - Prevention of postnatal mental health problems in women: knowledge exchange in
      primary care in Victoria, Australia.
AB  - ISSUE ADDRESSED: What Were We Thinking (WWWT) is a psychoeducation group program
      for the primary prevention of postnatal mental health problems in women. It
      addresses two neglected risks for postnatal depression and anxiety: unsettled
      infant behaviour and adjustments in the partner relationship after the birth of a
      first baby. WWWT has evidence of efficacy when facilitated by specialist nurses.
      It is designed to be facilitated by trained nurses as part of standard postnatal
      primary care. The aim of this study is to assess nurses' understanding of their
      role in prevention of postnatal mental health problems, the requirements for and
      feasibility of implementing WWWT, and nurses' current practice and specific
      training needs. METHODS: Maternal and Child Health (MCH) coordinators emailed
      nurses at all Victorian MCH centres an invitation to participate in a study about
      parent-infant mental health. Semi-structured interviews and group discussions
      were conducted. Responses were analysed thematically. RESULTS: MCH nurses
      demonstrated a willingness to implement a structured mental health-promotion
      intervention into clinical practice. Successful implementation will require
      changes to enable routine attendance of fathers at group sessions and
      recommendations to parents about the use of infant behaviour management
      strategies. CONCLUSIONS: This study contributes to comprehensive knowledge
      exchange about the implementation of a complex intervention in standard primary
      care. This knowledge is essential for generating practice-based evidence of the
      WWWT mental health-promotion program's effectiveness. SO WHAT?: The findings will
      inform a training program for WWWT nurse facilitators and the protocol for a
      cluster randomised control trial (RCT) to test the effectiveness of WWWT in
      standard postnatal care.

PMID- 25773161
TI  - The kynurenine pathway and neurodegenerative disease.
AB  - Neuroactive metabolites of the kynurenine pathway (KP) of tryptophan degradation
      have been closely linked to the pathogenesis of several neurodegenerative
      diseases. Tryptophan is an essential amino acid required for protein synthesis,
      and in higher eukaryotes is also converted into the key neurotransmitters
      serotonin and tryptamine. However, in mammals >95% of tryptophan is metabolized
      through the KP, ultimately leading to the production of nicotinamide adenosine
      dinucleotide (NAD(+)). A number of the pathway metabolites are neuroactive; e.g.
      can modulate activity of several glutamate receptors and generate/scavenge free
      radicals. Imbalances in absolute and relative levels of KP metabolites have been
      strongly associated with neurodegenerative disorders including Huntington's,
      Alzheimer's, and Parkinson's diseases. The KP has also been implicated in the
      pathogenesis of other brain disorders (e.g. schizophrenia, bipolar disorder), as
      well as several cancers and autoimmune disorders such as HIV. Pharmacological and
      genetic manipulation of the KP has been shown to ameliorate neurodegenerative
      phenotypes in a number of model organisms, suggesting that it could prove to be a
      viable target for the treatment of such diseases. Here, we provide an overview of
      the KP, its role in neurodegeneration and the current strategies for therapeutic
      targeting of the pathway. 

PMID- 25773162
TI  - Neuroprotective effects of dietary restriction: Evidence and mechanisms.
AB  - Dietary restriction (DR, in the form of reduced calorie intake or alternate
      fasting with overall normal energy supply) elicits cell protective responses in
      nearly all tissues and organs including brain, and extends lifespan in a fashion
      that is conserved from the simplest model organisms to mammals and non-human
      primates. Importantly, studies on DR promise to reveal novel strategies to
      prolong healthspan and prevent age-related disorders in human beings. The present
      review focuses on the neuroprotective actions of DR as demonstrated by
      accumulating experimental and encouraging albeit still limited clinical and
      epidemiological data. Following an overview of the most relevant evidence for the
      benefit of DR on neurodegenerative disorders and brain aging and damage in
      animals and human beings, the article will address the major mechanisms currently
      believed to participate in these effects, at a tissue (antiinflammation, enhanced
      adult neurogenesis and neuronal plasticity) and cellular (autophagy and
      mitochondrial biogenesis) level. Then it will "zoom-in" on the molecular
      circuitries (AMPK/mTOR, Sirtuins, CREB/Sirt1) whereby neuronal cells perceive the
      reduced availability of nutrients and translate this information into protective
      adaptive responses. As a further development of this aspect, the emerging
      connection between cell metabolism and chromatin remodeling will be analyzed,
      together with its relevance for our understanding of how food intake affects
      neuronal gene expression and brain health. 

PMID- 25773163
TI  - Determinants of surgical resection for pancreatic neuroendocrine tumors.
AB  - Pancreatic neuroendocrine tumors (pNETs) include functioning and non-functional
      tumors. Functioning tumors consist of tumors that produce a variety of hormones
      and their clinical effects. Therefore, determinants of resection of pNETs should
      be discussed for each group of tumors. Less than 10% of insulinomas are
      malignant, therefore more than 90% of the cases can be cured by surgical
      resection. Lymphadenectomy is generally not necessary in insulinoma operation. If
      preoperative localization of the insulinoma is completed, enucleation from the
      pancreatic body or tail, and distal pancreatectomy can be performed safely by
      laparoscopy. When preoperative localization of a sporadic insulinoma is not
      confirmed, surgical exploration is needed. Intraoperative localization of a
      tumor, intraoperative insulin sampling and frozen section are required. The
      crucial purpose of surgical resection is to control inappropriate insulin
      secretion by removing all insulinomas. Gastrinomas are usually located in the
      duodenum or pancreas, which secrete gastrin and cause Zollinger-Ellison syndrome
      (ZES). Duodenal gastrinomas are usually small, therefore they are not seen on
      preoperative imaging studies or endoscopic ultrasound, and can be found only at
      surgery if a duodenotomy is performed. In addition, lymph node metastasis is
      found in 40-60% of cases. Therefore, the experienced surgeons should direct
      operation for gastrinomas. Surgical exploration with duodenotomy should be
      performed at a laparotomy. Other functioning pNETs can occur in the pancreas or
      in other locations. Curative resection is always recommended whenever possible
      after optimal symptomatic control of the clinical syndrome by medical treatment.
      Indications for surgery depend on clinical symptom control, tumor size, location,
      extent, malignancy and presence of metastasis. A lot of non-functioning pNETs are
      found incidentally according to the quality improvement of imaging techniques.
      Localized, small, malignant non-functioning pNETs should be operated on
      aggressively, while in possibly benign tumors smaller than 2 cm the surgical risk
      benefit ratio should be carefully weighted. Surgical liver resection is generally
      proposed in curative intent to all patients with operable metastases from G1 or
      G2 pNET. The benefits of surgical resection of liver metastases have been
      demonstrated in terms of overall survival and quality of life. Complete resection
      is associated with better long-term survival. 

PMID- 25773165
TI  - Growth factors and IL-17 in hereditary angioedema.
AB  - Hereditary angioedema (HAE) is a rare autosomal dominant disorder, due to C1
      inhibitor deficiency, which causes episodic swellings of subcutaneous tissues,
      bowel walls and upper airways which are disabling and potentially life
      threatening. We evaluated n = 17 patients with confirmed HAE diagnosis in basal
      and crisis state and n = 19 healthy subjects. The samples were tested for IL-17,
      FGFb, G-CSF and GM-CSF, using Bio-plex kit. Data analysis was performed via
      nonparametric Spearman's correlations and two sets of linear mixed models. When
      comparing HAE subjects during basal and crisis states, we found out significantly
      (i.e., p value <0.05) higher values in crisis states rather than in basal states
      for the three growth factors and cytokine IL-17. When comparing healthy subjects
      versus HAE patients at basal state, we found out significantly higher values in
      HAE subjects only for GM-CSF, FGFb and IL-17, but not for G-CSF. In HAE patients,
      there is a connection between IL-17 and growth factors. The low-grade
      inflammation in absence of attacks is demonstrated by constant higher amount of
      IL-17, FGFb and GM-CSF with respect to healthy patients. This could indicate that
      in this disease there is a level of activation that maintains the system in a
      "tick-over state," that can be activate by several stimuli that are able to
      induce a increase in inflammatory mediators during the acute attack. 

PMID- 25773166
TI  - Successful embolization in childhood hemoptysis due to abnormal systemic arterial
      bleeding of the lung and review of the literature.
AB  - BACKGROUND AND AIMS: Hemoptysis in children is a rare but potentially life
      threatening symptom of an underlying respiratory tract abnormality. Hemoptysis,
      when massive and untreated, has a mortality rate of more than 50%. With
      interventional radiological procedures and surgery, this rate has dropped to 7%
      18%. The experience with bronchial arterial embolization in childhood is very
      limited; only a few case reports with short-term follow-up have been reported.
      METHODS: We report herein two patients with massive hemoptysis due to abnormal
      systemic arterial bleeding of the lung; neither patient had any lung or systemic
      disease. In both cases, the bleeding was controlled with endovascular
      embolization. The first case had bronchopulmonary arterial anastomosis and
      represents the first reported case with this anomaly. The second case had
      recurrent massive hemoptysis due to bronchial artery bleeding, and repeat
      embolization was performed. RESULTS: Both of these children had rare vascular
      anomalies without parenchymal lung disease and were treated successfully with
      bronchial arterial embolization. CONCLUSION: Massive hemoptysis due to abnormal
      systemic bleeding of the lung in the absence of parenchymal disease is an
      uncommon and severe symptom in childhood. Embolization can be a treatment option
      in children with abnormal vasculature bleeding and can be repeated safely when
      needed.

PMID- 25773167
TI  - SiRNA knockdown of the DEK nuclear protein mRNA enhances apoptosis and
      chemosensitivity of canine transitional cell carcinoma cells.
AB  - Transitional cell carcinoma (TCC) in dogs is an aggressive malignant neoplasm,
      originating in the epithelium of the urinary bladder. The DEK nuclear protein is
      overexpressed in several types of human bladder cancer, where it is involved in
      chromatin reconstruction, gene transcription and apoptosis. Since DEK represents
      a potential therapeutic target for canine TCC, this study was designed to
      investigate DEK expression in canine TCC and to determine the effects of DEK mRNA
      silencing on TCC cells in vitro. The gene expression profiles of seven selected
      cancer-associated genes was assessed in four canine TCC cell lines and expression
      of DEK protein was evaluated in bladder tissue biopsies from healthy dogs and
      those affected with cystitis or TCC. After transfection of four canine TCC cell
      lines with DEK-specific or scrambled siRNA, annexin V staining was performed to
      evaluate apoptosis, and methylthiazole tetrazolium assays were performed to
      assess both cell viability and sensitivity to carboplatin. DEK mRNA expression
      was relatively high in canine TCC cells and expression of the DEK protein was
      significantly greater in TCC tumours compared with the other tissue samples.
      After transfection with DEK-specific siRNA, apoptosis, cell growth inhibition,
      and enhanced sensitivity to carboplatin were observed in all TCC cells assessed.
      These research findings suggest that DEK could be a potential therapeutic target
      for canine TCC.

PMID- 25773169
TI  - Radiation in combination with immune-checkpoint inhibitors.

PMID- 25773168
TI  - beta-Lactam antibiotic-degrading enzymes from non-pathogenic marine organisms: a
      potential threat to human health.
AB  - Metallo-beta-lactamases (MBLs) are a family of Zn(II)-dependent enzymes that
      inactivate most of the commonly used beta-lactam antibiotics. They have emerged
      as a major threat to global healthcare. Recently, we identified two novel MBL
      like proteins, Maynooth IMipenemase-1 (MIM-1) and Maynooth IMipenemase-2 (MIM-2),
      in the marine organisms Novosphingobium pentaromativorans and Simiduia
      agarivorans, respectively. Here, we demonstrate that MIM-1 and MIM-2 have
      catalytic activities comparable to those of known MBLs, but from the pH
      dependence of their catalytic parameters it is evident that both enzymes differ
      with respect to their mechanisms, with MIM-1 preferring alkaline and MIM-2 acidic
      conditions. Both enzymes require Zn(II) but activity can also be reconstituted
      with other metal ions including Co(II), Mn(II), Cu(II) and Ca(II). Importantly,
      the substrate preference of MIM-1 and MIM-2 appears to be influenced by their
      metal ion composition. Since neither N. pentaromativorans nor S. agarivorans are
      human pathogens, the precise biological role(s) of MIM-1 and MIM-2 remains to be
      established. However, due to the similarity of at least some of their in vitro
      functional properties to those of known MBLs, MIM-1 and MIM-2 may provide
      essential structural insight that may guide the design of as of yet elusive
      clinically useful MBL inhibitors. 

PMID- 25773170
TI  - First biosimilar drug approved in the USA.

PMID- 25773171
TI  - Bortezomib treatment for patients with mantle-cell lymphoma.

PMID- 25773172
TI  - Seasonal DXA-measured body composition changes in professional male soccer
      players.
AB  - This work investigated changes in body composition of professional soccer players
      attending an Italian Serie A club across the competitive season; it is original
      insofar as body composition was assessed at multiple time points across the
      season using the accurate three-compartment model provided by Dual-Energy X-Ray
      Absorptiometry (DXA). Thirty-one players (4 goalkeepers, 13 defenders, 8
      midfielders, 6 forwards) underwent DXA and anthropometry at pre-, mid- and end
      season. One operator measured whole body and regional body composition (fat mass,
      FM; fat-free soft tissue mass, FFSTM; mineral mass). Two players were excluded
      from analysis due to serious injury. Data were analysed with repeated measures
      ANOVA; factors were season time point and playing position. Results showed that
      whole-body FM and %FM significantly (P < 0.001) decrease at mid-season (-11.9%; 
      1.3%, respectively) and end-season (-8.3%; -0.8%, respectively) whereas FFSTM
      significantly (P < 0.001) increase at mid-season (+1.3%) and end-season (+1.5%).
      Limited, but significant changes took place in bone mineral content. Some
      regional (upper and lower limbs, trunk) differences in the pattern of body
      composition changes across the season were also found. Changes were similar for
      all playing positions. It was concluded that professional soccer players undergo
      changes in their FM, FFSTM, and mineral mass across the season with some regional
      variations, irrespective of the playing position. Changes are mostly positive at
      mid-season, possibly due to difference in training between the first and second
      phase of the season. 

PMID- 25773173
TI  - Modelling partially cross-classified multilevel data.
AB  - This article proposes an approach to modelling partially cross-classified
      multilevel data where some of the level-1 observations are nested in one random
      factor and some are cross-classified by two random factors. Comparisons between a
      proposed approach to two other commonly used approaches which treat the partially
      cross-classified data as either fully nested or fully cross-classified are
      completed with a simulation study. Results show that the proposed approach
      demonstrates desirable performance in terms of parameter estimates and
      statistical inferences. Both the fully nested model and the fully cross
      classified model suffer from biased estimates of some variance components and
      statistical inferences of some fixed effects. Results also indicate that the
      proposed model is robust against cluster size imbalance. 

PMID- 25773175
TI  - Evidence for a profound remodeling of skeletal muscle and its microvasculature in
      sickle cell anemia.
AB  - Sickle cell anemia (SCA) is a hemoglobinopathy leading to major hematologic,
      hemorheologic, and hemodynamic disorders that induce various complications,
      including organ failure, and ultimately lead to death. Here, we assessed for the
      first time repercussions of SCA on skeletal muscle and its microvasculature.
      Twenty-seven sedentary Cameroonian volunteer men participated in the study. They
      were assigned to one of three groups according to their hemoglobin status
      (healthy control subjects, n = 10; sickle cell trait carriers, n = 10; and SCA
      patients, n = 7) and underwent muscle biopsy of the vastus lateralis. SCA was
      associated with microvessel rarefaction, decrease in capillary tortuosity, and
      widening of microvessel diameter. The absence of capillary wall reinforcement was
      shown by lack of wall thickening and lack of fibrous tissue or smooth muscle in
      their constitution. We also observed changes in fiber type distribution, muscle
      atrophy, an increase in satellite cell number, and a decrease in activity of
      creatine kinase and several oxidative enzymes. No signs of tissue necrosis,
      inflammatory stress, fibrosis, or segmented fibers were observed. The present
      study highlighted marked effects of SCA on microvascular, structural, and
      energetic characteristics of skeletal muscle. 

PMID- 25773174
TI  - p120-catenin expressed in alveolar type II cells is essential for the regulation
      of lung innate immune response.
AB  - The integrity of the lung alveolar epithelial barrier is required for the gas
      exchange and is important for immune regulation. Alveolar epithelial barrier is
      composed of flat type I cells, which make up approximately 95% of the gas
      exchange surface, and cuboidal type II cells, which secrete surfactants and
      modulate lung immunity. p120-catenin (p120; gene symbol CTNND1) is an important
      component of adherens junctions of epithelial cells; however, its function in
      lung alveolar epithelial barrier has not been addressed in genetic models. Here,
      we created an inducible type II cell-specific p120-knockout mouse (p120EKO). The
      mutant lungs showed chronic inflammation, and the alveolar epithelial barrier was
      leaky to (125)I-albumin tracer compared to wild type. The mutant lungs also
      demonstrated marked infiltration of inflammatory cells and activation of NF
      kappaB. Intracellular adhesion molecule 1, Toll-like receptor 4, and macrophage
      inflammatory protein 2 were all up-regulated. p120EKO lungs showed increased
      expression of the surfactant proteins Sp-B, Sp-C, and Sp-D, and displayed severe
      inflammation after pneumonia caused by Pseudomonas aeruginosa compared with wild
      type. In p120-deficient type II cell monolayers, we observed reduced
      transepithelial resistance compared to control, consistent with formation of
      defective adherens junctions. Thus, although type II cells constitute only 5% of
      the alveolar surface area, p120 expressed in these cells plays a critical role in
      regulating the innate immunity of the entire lung. 

PMID- 25773176
TI  - Context-Dependent Regulation of Collagen XVII Ectodomain Shedding in Skin.
AB  - Pemphigoid is a common autoimmune blistering disorder in which autoantibodies
      target transmembrane collagen XVII (COL17), a component of hemidesmosomes in
      basal keratinocytes. The ectodomain of COL17 can be cleaved from the cell surface
      within the juxtamembranous extracellular NC16A domain, and, interestingly,
      certain autoantibodies of pemphigoid patients preferentially react with the shed
      ectodomain. These findings suggest that COL17 ectodomain shedding generates
      neoepitopes on the shed form; however, the regulatory mechanism of the shedding
      in in vivo skin and the pathogenicity of the neoepitope-targeting antibodies
      still are uncertain. To address these issues, we produced rabbit antibodies
      specifically reacting with N-terminal cleavage sites of the shed COL17
      ectodomain. The antibodies showed that certain amounts of the human COL17
      ectodomain are cleaved physiologically at Gln(525) in in vivo skin. In contrast,
      migrating human keratinocytes cleave COL17 at Leu(524) but not at Gln(525). The
      passive transfer of antibodies reacting with an N-terminal cleavage site of the
      mouse COL17 ectodomain into neonatal wild-type mice failed to induce blister
      formation, even though the antibodies bound to the dermal-epidermal junctions,
      indicating that cleavage site-specific antibodies have reduced or absent
      pathogenicity for blister formation. This study shows the ectodomain shedding of
      COL17 to be a physiological event in in vivo human skin that probably generates
      nonpathologic epitopes on the cleavage sites.

PMID- 25773177
TI  - PPARalpha-Deficient ob/ob Obese Mice Become More Obese and Manifest Severe
      Hepatic Steatosis Due to Decreased Fatty Acid Oxidation.
AB  - Obesity poses an increased risk of developing metabolic syndrome and closely
      associated nonalcoholic fatty liver disease, including liver cancer. Satiety
      hormone leptin-deficient (ob/ob) mice, considered paradigmatic of nutritional
      obesity, develop hepatic steatosis but are less prone to developing liver tumors.
      Sustained activation of peroxisome proliferator-activated receptor alpha
      (PPARalpha) in ob/ob mouse liver increases fatty acid oxidation (FAO), which
      contributes to attenuation of obesity but enhances liver cancer risk. To further
      evaluate the role of PPARalpha-regulated hepatic FAO and energy burning in the
      progression of fatty liver disease, we generated PPARalpha-deficient ob/ob
      (PPARalpha(Delta)ob/ob) mice. These mice become strikingly more obese compared to
      ob/ob littermates, with increased white and brown adipose tissue content and
      severe hepatic steatosis. Hepatic steatosis becomes more severe in fasted
      PPARalpha(Delta)ob/ob mice as they fail to up-regulate FAO systems.
      PPARalpha(Delta)ob/ob mice also do not respond to peroxisome proliferative and
      mitogenic effects of PPARalpha agonist Wy-14,643. Although PPARalpha(Delta)ob/ob
      mice are severely obese, there was no significant increase in liver tumor
      incidence, even when maintained on a diet containing Wy-14,643. We conclude that
      sustained PPARalpha activation-related increase in FAO in fatty livers of obese
      ob/ob mice increases liver cancer risk, whereas deletion of PPARalpha in ob/ob
      mice aggravates obesity and hepatic steatosis. However, it does not lead to liver
      tumor development because of reduction in FAO and energy burning.

PMID- 25773178
TI  - Identification and characterization of a member of Rab subfamily, Rab8, from
      Clonorchis sinensis.
AB  - The Rabs act as a binary molecular switch that utilizes the conformational
      changes associated with the GTP/GDP cycle to elicit responses from target
      proteins. It regulates a broad spectrum of cellular processes including cell
      proliferation, cytoskeletal assembly, and intracellular membrane trafficking in
      eukaryotes. The Rab8 from Clonorchis sinensis (CsRab8) was composed of 199 amino
      acids. The deduced amino acid sequence shared above 50% identities with other
      species from trematode, tapeworm, mammal, insecta, nematode, and reptile,
      respectively. The homologous analysis of sequences showed the conservative
      domains: G1 box (GDSGVGKS), G2 box (T), G3 box (DTAG), G4 box (GNKCDL), and G5
      box. In addition, the structure modeling had also shown other functional domains:
      GTP/Mg(2+) binding sites, switch I region, and switch II region. A phylogenic
      tree analysis indicated that the CsRab8 was clustered with the Rab from
      Schistosoma japonicum, and trematode and tapeworm came from the same branch,
      which was different from an evolutional branch built by other species, such as
      mammal animal, insecta, nematode, and reptile. The recombinant CsRab8 protein was
      expressed in Escherichia coli and the purified protein was a soluble molecule by
      12% sodium dodecyl sulfate polyacrylamide gel electrophoresis analysis. CsRab8
      was identified as a component of excretory/secretory products of C. sinensis by
      western blot analysis. The transcriptional level of CsRab8 at metacercaria stage
      was the highest at the four stages and higher by 56.49-folds than that at adult
      worm, 1.23-folds than that at excysted metacercaria, and 2.69-folds than that at
      egg stage. Immunohistochemical localization analysis showed that CsRab8 was
      specifically distributed in the tegument, vitellarium, eggs, and testicle of
      adult worms, and detected on the vitellarium and tegument of metacercaria.
      Combined with the results, CsRab8 is indispensable for survival and development
      of parasites, especially for regulating excretory/secretory products secretion.

PMID- 25773179
TI  - Zoonotic parasites in feces and fur of stray and private dogs from Italy.
AB  - The present study evaluated the occurrence of zoonotic parasites in feces and on
      fur of stray and private dogs living in Italy. Individual fecal samples collected
      from 117 and 385 kenneled (i.e., rescue shelter) and privately owned dogs,
      respectively, were examined by conventional copromicroscopy. Samples positive for
      Giardia duodenalis and Cryptosporidium spp. were subjected to further genetic
      characterization. Additionally, 174 fur samples of private and kenneled dogs
      living in the same area, 27 of which were also subjected to copromicroscopical
      examinations, were examined for the presence and viability of parasite elements.
      Out of 502 fecal samples, forty-one (8.2%) scored positive for G. duodenalis
      cysts while one (0.2%) for Cryptosporidium oocysts. Nine private dogs were
      molecularly positive for G. duodenalis assemblage C (n. 7), assemblage D (n. 1),
      and assemblages C + D (n. 1), while 11 kenneled dogs were positive for assemblage
      C (n. 8), assemblage D (n. 1), and assemblages C + D (n. 2). Cryptosporidium spp.
      were identified as C. canis in a private dog. One hundred and seventy-two dogs
      (34.3%), i.e., 92 private and 80 kenneled, were positive for zoonotic nematodes:
      Toxocara canis (6.6 %), Ancylostoma caninum (6.8%), and Capillaria aerophila
      (0.6%). Unviable eggs of Toxocara spp. were found on the hair of five (2.9%)
      private dogs. The present findings indicate that canine feces from both private
      and kenneled animals may contain zoonotic parasites and may be a potential risk
      for humans and other animals, especially when they contaminate the environment.
      The role of dog fur as source of human infections should be further investigated.

PMID- 25773180
TI  - Combination of cell culture and qPCR to assess the efficacy of different
      anticoccidials on Eimeria tenella sporozoites.
AB  - Three in vitro studies were designed to develop an assay for anticoccidial
      efficacy by use of laboratory (Houghton) and field (T-376) Eimeria tenella
      strains. In study (1), minimum inhibitory concentrations (MICs) of monensin
      (Mon), maduramicin (Mad), salinomycin (Sal), and lasalocid (Las) were determined
      that are able to inhibit more than 50% of sporozoites in host cell (Madin-Darby
      bovine kidney (MDBK)) penetration and more than 95% of Houghton sporozoites
      development to mature merozoites (treatment time 24 h) using quantitative real
      time PCR (qPCR). MICs were 0.5, 2.5, 1, and 0.5 MUg/ml for Mon, Mad, Sal, and
      Las, respectively. Applying the previous MIC on T-376 strain revealed a different
      sensitivity profile. Mad reduced T-376 gene copies by only 89.3% after 96 h of
      infection. In study (2), Houghton strain sporozoites were incubated with MIC of
      the different tested ionophores for 2 and 4 h, respectively; afterwards, their
      ability to invade MDBK cells was determined using phase-contrast microscopy and
      qPCR. Treatment of sporozoites with ionophores for 4 h resulted in significant
      inhibition of invasion compared with non-treated parasites as assessed both by
      microscopy as well as qPCR. Inhibition rates for Mon, Mad, Sal, and Las were
      90.2, 75.0, 88.3, and 82.6% using phase-contrast microscopy and 83.9, 81.4, 85.8,
      and 75.4% using qPCR, respectively. T-376 sporozoite invasion into MDBK cells was
      reduced to 48.9% by Mad. Study (3) was conducted to determine inhibition exerted
      by toltrazuril (Tol). Tol at 5 MUg/ml reduced reproduction of Houghton strain by
      95%, whereas T-376 was only reduced by 86.5%. The presented experiments indicate
      that infectivity inhibition of sporozoites incubated for 4 h with anticoccidials
      and development inhibition after 96 h of infection by qPCR are suitable means to
      assess sensitivity of E. tenella strains to anticoccidials.

PMID- 25773181
TI  - Neurotoxocarosis alters myelin protein gene transcription and expression.
AB  - Neurotoxocarosis is an infection of the central nervous system caused by
      migrating larvae of the common dog and cat roundworms (Toxocara canis and
      Toxocara cati), which are zoonotic agents. As these parasites are prevalent
      worldwide and neuropathological and molecular investigations on neurotoxocarosis
      are scare, this study aims to characterise nerve fibre demyelination associated
      with neurotoxocarosis on a molecular level. Transcription of eight myelin
      associated genes (Cnp, Mag, Mbp, Mog, Mrf-1, Nogo-A, Plp1, Olig2) was determined
      in the mouse model during six time points of the chronic phase of infection using
      qRT-PCR. Expression of selected proteins was analysed by Western blotting or
      immunohistochemistry. Additionally, demyelination and neuronal damage were
      investigated histologically. Significant differences (p <= 0.05) between
      transcription rates of T. canis-infected and uninfected control mice were
      detected for all analysed genes while T. cati affected five of eight investigated
      genes. Interestingly, 2', 3 '-cyclic nucleotide 3'-phosphodiesterase (Cnp) and
      myelin oligodendrocyte glycoprotein (Mog) were upregulated in both T. canis- and
      T. cati-infected mice preceding demyelination. Later, CNPase expression was
      additionally enhanced. As expected, myelin basic protein (Mbp) was downregulated
      in cerebra and cerebella of T. canis-infected mice when severe demyelination was
      present 120 days post infectionem (dpi). The transcriptional pattern observed in
      the present study appears to reflect direct traumatic and hypoxic effects of
      larval migration as well as secondary processes including host immune reactions,
      demyelination and attempts to remyelinate damaged areas. 

PMID- 25773182
TI  - Angelica sinensis (Umbelliferae) with proven repellent properties against Aedes
      aegypti, the primary dengue fever vector in Thailand.
AB  - Botanical resources with great diversity in medicinal and aromatic plants are a
      rich and reliable source for finding insect repellents of plant origin, which are
      widely popular among today's consumers. Although some herbal-based repellents
      have been proven comparable to or even better than synthetics, commercially
      available natural repellents generally tend to be expensive, with short-lived
      effectiveness. This critical flaw leads to ongoing research for new and effective
      repellents, which provide longer protection against vector and nuisance-biting
      insects, while remaining safe, user friendly, and reasonably priced. This study
      aimed to evaluate the repellent activity of plant-derived products against the
      primary dengue vector, Aedes aegypti, by following the human bait technique of
      World Health Organization guidelines. Preliminary laboratory screening tests for
      repellency of 33 plant species clearly demonstrated Angelica sinensis as the most
      effective repellent from each kind of extracted product, with its essential oil
      and ethanolic extract having median complete protection times of 7.0 h (6.0-7.5)
      and 2.5 h (2.0-2.5), respectively. Due to its low yield (0.02 %), pungent smell,
      and little cause of irritation, A. sinensis essential oil did not qualify as a
      candidate for further repellent assessment. However, subsequent extractions of A.
      sinensis with different organic solvents of increasing polarity provided four
      extractants with varying degrees of repellency against A. aegypti. The hexane
      extract of A. sinensis provided excellent repellency, with a median complete
      protection time of 7.5 h (6.5-8.5), which was longer than that of ethanol (2.5,
      2.0-2.5 h), acetone (1.75, 0.5-2.5 h), and methanol extracts (0.5, 0-1.0 h). By
      being the most effective product, A. sinensis hexane extract gave significant
      protection comparable to that of its essential oil and the standard synthetic
      repellent, N,N-diethyl-3-methylbenzamide (DEET: 6.25, 5.0-6.5 h). Qualitative gas
      chromatography/mass spectrometry analysis demonstrated the presence of phthalides
      and phthalates, including 3-N-butylphthalide, butylidenephthalide, ligustilide,
      and di-iso-octyl phthalate, as the principal constituents in A. sinensis
      products. The success of A. sinensis products, particularly that of hexane
      extract, has proved their potential as bioactive candidates in the next step for
      developing and producing alternative natural repellents with commercial
      aspirations.

PMID- 25773183
TI  - In vivo and in vitro efficacies of mebendazole, mefloquine and nitazoxanide
      against cyst echinococcosis.
AB  - Echinococcus granulosus is a cestode parasite. The metacestode stage causes
      cystic echinococcosis (CE) mainly in the human liver and lung. Current
      chemotherapy against CE is based on mebendazole and albendazole. However,
      benzimidazoles result in a low cure rate or are ineffective in many patients;
      therefore, novel compounds for the treatment of this disease have been studied.
      Mefloquine was reported to be dramatically effective on cultured Echinococcus
      multilocularis metacestodes in vitro. And, nitazoxanide has a prominent
      protoscolicidal effect. However, these compounds have no impact on the growth of
      cysts harbored in mice. In this study, we investigated the in vitro and in vivo
      efficacy of mebendazole, mefloquine, and nitazoxanide against E. granulosus
      protoscoleces, germinal cells, and infected mice. The effect of mebendazole on
      protoscoleces and germinal cell was proved to be dose-dependent in vitro. And, a
      reduction of the cyst weight was also the found after oral application of
      mebendazole to infected mice. Mefloquine (5 and 10 MUg/ml) caused death within 24
      h of protoscoleces and germinal cells in vitro, whereas a lower concentration of
      1 MUg/ml was ineffective. In mice infected with E. granulosus, oral mefloquine
      (200 and 400 mg/kg twice weekly for 2 weeks) showed no reduction in parasite
      weight. Without affecting the viability of germinal cells and the growth of
      hydatid cysts, nitazoxanide only showed protoscolicidal effects in infected mice.
      In conclusion, mebendazole, mefloquine, and nitazoxanide showed various effects
      on E. granulosus under different conditions. These drugs could be useful to some
      extent in the treatment of CE.

PMID- 25773184
TI  - Ectoparasite load in the crested porcupine Hystrix cristata Linnaeus, 1758 in
      Central Italy.
AB  - The crested porcupine Hystrix cristata is a large body-sized rodent, occurring in
      Europe only in the Italian Peninsula, where it may have been introduced in early
      Medieval times. Its parasite fauna is currently poorly known and limited to few
      anecdotal observations. We have analyzed the ectoparasite load of 165 crested
      porcupines from Tuscany and Latium (Central Italy). Both captured and road-killed
      individuals were checked for fleas and ticks. Overall, only 39 porcupines were
      infested by four species of ticks and five of fleas. Abundance of ectoparasites
      was higher in areas with higher habitat richness, with respect to densely wooded
      areas. The most frequent species was the flea Pulex irritans (25%), whose
      prevalence peaked in winter probably because of optimal abiotic conditions in the
      porcupine's den. The remaining species of both hard ticks (Rhipicephalus bursa,
      Pholeoixodes hexagonus, and Ixodes ventalloi) and fleas (Paraceras melis,
      Ctenocephalides canis, Dasypsyllus gallinulae, and Hystrichopsylla talpae), all
      with prevalence lower than 5%, could be due to den sharing with other
      vertebrates, mainly carnivores such as, e.g., red foxes and badgers. The second
      most prevalent species was the generalist tick Ixodes ricinus (21%). An adult
      male-biased parasitism for ticks has been detected, suggesting a possible role of
      testosterone related immune-depressive effect. The low richness in dominant
      ectoparasite species, built up by locally acquired generalist taxa, provides
      support to the allochthonous origin of this rodent in Italy.

PMID- 25773185
TI  - Differential influence of urbanisation on Coccidian infection in two passerine
      birds.
AB  - Urbanisation has the potential to increase the risk of parasitism on wildlife.
      Although some ectoparasite groups appear unaffected, different responses are
      hypothesised for parasites with simpler life histories such as gastrointestinal
      parasites. Red-browed finches (RBF) and the superb fairywrens (SFW), two native
      passerine birds affected by urbanisation, were examined for Coccidian parasites
      along an urbanisation gradient in New South Wales, Australia, in order to detect
      if prevalence might be directly related to the degree of urbanisation. Influence
      of urbanisation on Coccidian infection was differential. In RBF, the prevalence
      of Isospora increased significantly in more urbanised areas but prevalence did
      not change between breeding and non-breeding seasons. In contrast, in SFW, the
      degree of urbanisation did not significantly change with the degree of
      urbanisation, and season exhibited no significant effects on the prevalence of
      coccidians. Diet, behaviour and habits are suspected to be the most influential
      factors on the variation seen between both species where granivorous and
      gregarious species are significantly infected. Since the dynamics of urban
      wildlife-pathogen interactions is largely unexplored, more studies are needed to
      corroborate if this pattern of Isospora infections can be extended to other
      passerine birds in cities from Australia and overseas. 

PMID- 25773186
TI  - Molecular characterization of Cryptosporidium spp. in domestic pigeons (Columba
      livia domestica) in Guangdong Province, Southern China.
AB  - To investigate the prevalence and assess the zoonotic transmission burden of
      Cryptosporidium species in domestic pigeons in Guangdong Province, Southern
      China, 244 fecal samples were collected from four pigeon breeding farms between
      June 2012 and March 2013. Cryptosporidium oocysts were purified by Sheather's
      sugar flotation technique and characterized by DNA sequencing of small subunit
      ribosomal RNA (SSU rRNA) gene. Cryptosporidium species were determined by
      comparison of sequences with corresponding Cryptosporidium sequences in GenBank
      and phylogenetic analysis using neighbor-joining (NJ) in MEGA5.2. The overall
      prevalence of Cryptosporidium infection in domestic pigeons in Guangdong Province
      was 0.82% (2/244). Two Cryptosporidium species, namely Cryptosporidium baileyi
      and Cryptosporidium meleagridis, were identified in Huizhou and Chaozhou farm,
      respectively. These findings confirmed the existence of C. meleagridis infection
      in domestic pigeons in China for the first time and provided base-line
      information for further studies to evaluate the public health risk from pigeon to
      human.

PMID- 25773187
TI  - Robust spectrometer-based methods for characterizing radiant exitance of dental
      LED light curing units.
AB  - OBJECTIVES: Firstly, to assess light output, from a representative range of
      dental light curing units (LCUs), using a new portable spectrometer based
      instrument (checkMARCTM) compared with a "gold standard" method. Secondly, to
      assess possible inconsistency between light output measurements using three
      different laboratory-grade thermopile instruments. METHODS: The output of four
      blue-dental LCUs and four polywave blue-and-violet-LCUs was measured with two
      spectrometer-based systems: a portable spectrometer instrument and a benchtop
      Integrating Sphere fiber-coupled spectrometer system. Power output was also
      recorded with three thermopiles according to ISO 10650-2. Beam profile images
      were recorded of LCU output to assess for spatial and spectral beam uniformity.
      RESULTS: Power recorded with the portable spectrometer instrument closely matched
      the 'gold standard' Integrating Sphere apparatus calibrated according to
      International Standards. Radiant exitance for the eight LCUs differed
      significantly between the three thermopiles. Light source to thermopile sensor
      distance influenced recorded power significantly (p<0.05), indicating the severe
      limitations of thermopiles for absolute measurements. Polywave LCU beam profiles
      demonstrated output spectral heterogeneity. SIGNIFICANCE: Spectrometer-based
      methods are capable of overcoming the limitations inherent with thermopile-based
      measurement techniques. Spectrometer based measurements can fulfill the intention
      of ISO 10650.

PMID- 25773188
TI  - Clinical effectiveness of direct anterior restorations--a meta-analysis.
AB  - OBJECTIVES: This is the first meta-analysis on the efficacy of composite resin
      restorations in anterior teeth. The objective of the present meta-analysis was to
      verify whether specific material classes, tooth conditioning methods and
      operational procedures influence the result for Class III and Class IV
      restorations. MATERIAL AND METHODS: The database SCOPUS and PubMed were searched
      for clinical trials on anterior resin composites without restricting the search
      to the year of publication. The inclusion criteria were: (1) prospective clinical
      trial with at least 2 years of observation; (2) minimal number of restorations at
      last recall=20; (3) report on drop-out rate; (4) report of operative technique
      and materials used in the trial, and (5) utilization of Ryge or modified Ryge
      evaluation criteria. For the statistical analysis, a linear mixed model was used
      with random effects to account for the heterogeneity between the studies. p
      Values smaller than 0.05 were considered to be significant. RESULTS: Of the 84
      clinical trials, 21 studies met the inclusion criteria, 14 of them for Class III
      restorations, 6 for Class IV restorations and 1 for closure of diastemata; the
      latter was included in the Class IV group. Twelve of the 21 studies started
      before 1991 and 18 before 2001. The estimated median overall success rate
      (without replacement) after 10 years for Class III composite resin restorations
      was 95% and for Class IV restorations 90%. The main reason for the replacement of
      Class IV restorations was bulk fractures, which occurred significantly more
      frequently with microfilled composites than with hybrid and macrofilled
      composites. Caries adjacent to restorations was infrequent in most studies and
      accounted only for about 2.5% of all replaced restorations after 10 years
      irrespective of the cavity class. Class III restorations with glass ionomer
      derivates suffered significantly more loss of anatomical form than did fillings
      with other types of material. When the enamel was acid-etched and no bonding
      agent was applied, significantly more restorations showed marginal staining and
      detectable margins compared to enamel etching with enamel bonding or the total
      etch technique; fillings with self-etching systems were in between of these two
      outcome variables. Bevelling of the enamel was associated with a significantly
      reduced deterioration of the anatomical form compared to no bevelling but not
      with less marginal staining or less detectable margins. The type of isolation
      (absolute/relative) had a statistically significant influence on marginal caries
      which, however, might be a random finding.

PMID- 25773189
TI  - Let there be More Light!

PMID- 25773190
TI  - Initial Experience with a New Image Integration Module Designed for Reducing
      Radiation Exposure During Electrophysiological Ablation Procedures.
AB  - INTRODUCTION: Reduction of radiation exposure during cardiac arrhythmia ablation
      procedures is desirable. We sought to evaluate the utility of a new image
      integration module (CARTOUNIVU(TM) ) in reducing fluoroscopy times and dosages
      during left atrial arrhythmia (LAA) and ventricular tachycardia (VT) ablation
      procedures. METHODS AND RESULTS: Consecutive patients undergoing LAA (n = 28)/VT
      (n = 13) ablation using the CARTOUNIVU(TM) module were included. Total
      fluoroscopy time, radiation dose (total dose area product [tDAP], effective dose
      [ED]), and procedure duration were evaluated. A retrospective cohort of patients
      who underwent LAA (n = 16)/VT(n = 8) ablation without the new image integration
      module served as a control group. The use of the new image integration module
      significantly reduced mean fluoroscopy time (5.2 minutes [IQR 1.9;6.8] in the LAA
      ablation UNIVU group vs. 28.2 minutes [IQR 15.3;37.8] in the control group,
      P<0.001; 9.8 minutes [IQR 4.5;13.1] vs. 25.5 minutes [IQR 14.1;30.9] for VT
      ablation, P = 0.013), tDAP (2,088 cGy*cm(2) [IQR 664;2911] vs. 5,893 cGy*cm(2)
      [IQR 3088;8483], P< 0.001 for LAA ablation; 3,917 cGy*cm(2) [IQR 948;4217] vs.
      12,377 cGy*cm(2) (IQR 3385;23157) for VT ablation patients, P = 0.025) and ED
      (4.1 mSv [IQR 1;5.8] vs. 11.8 mSv [IQR 6.2;16.9] for LAA ablation patients, P<
      0.001; 7.8 mSv [IQR 1.9;8.4] vs. 24.7 mSv [IQR 6.8;46.3] for VT ablation
      patients, P = 0.025). Procedure duration did not significantly change (174 +/- 45
      minutes vs. 197 +/- 36 minutes for LAA ablation, P = 0.083; 201 +/- 51 minutes
      vs. 201 +/- 63 minutes for VT ablation, P = 0.860). No serious adverse events
      related to the use of the CARTOUNIVU(TM) module occurred. CONCLUSIONS: The new
      image integration module significantly reduced total fluoroscopy time and mean
      radiation dose without influence in procedure duration during ablation of complex
      atrial and ventricular arrhythmias.

PMID- 25773191
TI  - Application of (19)  F time-domain NMR to measure content in fluorine-containing
      drug products.
AB  - It is necessary to show that the active content in the dosage form of drugs is
      within a certain narrow range of the label claim. In case of fluorinated drugs,
      the active content can be measured by high field solid state NMR because the
      excipients lack fluorine. To make NMR reachable to any laboratory, simple to use,
      and at a low cost, measurement of (19)  F nucleus using a 23 MHz (for (1) H) low
      field benchtop time-domain (TD) NMR was investigated. Three fluorinated drug
      products, cinacalcet, lansoprazole, and ciprofloxacin, were chosen for this
      study. The doses for these drug products range from 15 to 500 mg. The average
      drug content measured using (19)  F TD-NMR compares well with the reported label
      claims for the three drugs tested. (19)  F TD-NMR is a simple and non-destructive
      technique to measure drug content in tablets. In addition, the accessibility and
      simplicity of the technique makes it an excellent process analytical technology
      tool for development and manufacturing in the pharmaceutical industry. Copyright
      (c) 2015 John Wiley & Sons, Ltd. 

PMID- 25773193
TI  - The impact of events scale: a comparison of frequency versus severity approaches
      to measuring cancer-specific distress.
AB  - OBJECTIVE: The Impact of Events Scale (IES) is one of the most widely used
      measures of event-specific distress. The IES assesses the frequency with which
      respondents experience intrusive thoughts and avoidant behaviors over the past
      week. Our aim is to demonstrate the benefit of a severity-based measurement
      approach of the IES compared with a frequency-based measurement approach.
      METHODS: A mixed group of post-treatment cancer survivors (N = 325; M = 31.8
      years old) completed measures assessing quality of life (Functional Assessment of
      Cancer Therapy-General), psychological adjustment (Mental Health Inventory), and
      cancer-related distress (IES). The IES was keyed to the cancer experience and
      administered with standard (frequency) and modified (severity) response options.
      RESULTS: Classical reliability analyses and bifactor modeling were conducted on
      both versions of the IES. Reliability estimates suggest that the IES severity
      items were more highly intercorrelated than the IES frequency items. Both
      versions of the IES were highly correlated (r = 0.82), showing the presence of a
      dominant general factor. Bifactor modeling suggested that the severity items
      generally provided higher levels of discrimination than the frequency items.
      Validity correlations with the Functional Assessment of Cancer Therapy-General
      and Mental Health Inventory demonstrated that the IES severity performed as good
      as or better than the IES frequency. CONCLUSIONS: Given the high correlations and
      similarity in content, the IES severity items largely assess the same construct
      as the IES frequency items. However, IES severity items generally showed improved
      psychometric properties and similar or higher correlations with quality of life
      and psychological adjustment. The IES severity approach appears to be a more
      informative method for assessing cancer-specific distress.

PMID- 25773192
TI  - Clinical diagnoses and antimicrobials predictive of pediatric antimicrobial
      stewardship recommendations: a program evaluation.
AB  - BACKGROUND: The number of pediatric antimicrobial stewardship programs (ASPs) is
      increasing and program evaluation is a key component to improve efficiency and
      enhance stewardship strategies. OBJECTIVE: To determine the antimicrobials and
      diagnoses most strongly associated with a recommendation provided by a well
      established pediatric ASP. DESIGN AND SETTING: Retrospective cohort study from
      March 3, 2008, to March 2, 2013, of all ASP reviews performed at a free-standing
      pediatric hospital. METHODS: ASP recommendations were classified as follows: stop
      therapy, modify therapy, optimize therapy, or consult infectious diseases. A
      multinomial distribution model to determine the probability of each ASP
      recommendation category was performed on the basis of the specific antimicrobial
      agent or disease category. A logistic model was used to determine the odds of
      recommendation disagreement by the prescribing clinician. RESULTS: The ASP made
      2,317 recommendations: stop therapy (45%), modify therapy (26%), optimize therapy
      (19%), or consult infectious diseases (10%). Third-generation cephalosporins
      (0.20) were the antimicrobials with the highest predictive probability of an ASP
      recommendation whereas linezolid (0.05) had the lowest probability. Community
      acquired pneumonia (0.26) was the diagnosis with the highest predictive
      probability of an ASP recommendation whereas fever/neutropenia (0.04) had the
      lowest probability. Disagreement with ASP recommendations by the prescribing
      clinician occurred 22% of the time, most commonly involving community-acquired
      pneumonia and ear/nose/throat infections. CONCLUSIONS: Evaluation of our
      pediatric ASP identified specific clinical diagnoses and antimicrobials
      associated with an increased likelihood of an ASP recommendation. Focused
      interventions targeting these high-yield areas may result in increased program
      efficiency and efficacy.

PMID- 25773194
TI  - Mechanical force and tensile strain activated hepatic stellate cells and
      inhibited retinol metabolism.
AB  - OBJECTIVES: Hepatic stellate cells (HSCs), the principal producers of
      extracellular matrix proteins, play a major role in the development of liver
      fibrosis which is accompanied with elevated sinusoidal pressure and portal
      hypertension. We have isolated primary rat HSCs and investigated the effect of
      mechanical pressure and tensile strain on retinol metabolism in the cells.
      RESULTS: Mechanical force and tensile strain significantly increased the
      expression of alpha-smooth muscle actin (alpha-SMA) and collagen I, and notably
      inhibited the expression of cellular retinol-binding protein I (CRBP-I), lecithin
      retinol acyltransferase (LRAT), retinyl ester hydrolase (REH), retinoic acid
      receptor-beta (RAR-beta) and retinoid X receptor-alpha (RXR-alpha). Such effects
      were partially reversed by the retinoid X receptor antagonist, HX531, and the
      retinoic acid receptor antagonist, LE135. CONCLUSION: Mechanical force and
      tensile strain significantly activate HSCs by regulating the retinoid metabolic
      pathway. Activation of HSCs can therefore be manipulated through mechanical force
      and tensile strain in vitro.

PMID- 25773195
TI  - Surface display of highly-stable Desulfovibrio vulgaris carbonic anhydrase on
      polyester beads for CO2 capture.
AB  - OBJECTIVES: To engineer a recombinant Escherichia coli to produce
      polyhydroxyalkanoate biopolymer beads displaying carbonic anhydrase (CA) from
      Desulfovibrio vulgaris str. "Miyazaki F" (DvCA). RESULTS: The highest measured
      specific activity of the immobilised CA was 211 U/mg DvCA. The immobilised CA was
      thermostable, retaining 114 U/mg DvCA of activity after incubation at 90  degrees
      C for 1 h. Additionally, the immobilised CA tolerated 30 min incubations in a
      variety of pH conditions and was especially tolerant of alkaline conditions,
      retaining 131 U/mg DvCA of activity after pH 12 incubation. CONCLUSION: CA has a
      potential role in atmospheric CO2 mitigation strategies and the stability of the
      functionalised beads indicates suitability for use in industrial settings such as
      coal-fired power plants.

PMID- 25773196
TI  - Biodegradation of thifensulfuron-methyl by Ochrobactrum sp. in liquid medium and
      soil.
AB  - OBJECTIVES: Excessive use of thifensulfuron-methyl has raised concerns for
      environmental contamination and phytotoxicity to crops. Experiments were
      performed to isolate a microorganism that can degrade thifensulfuron-methyl and
      assess its effectiveness. RESULTS: A bacterial isolate, Ochrobactrum sp. ZWS16,
      capable of degrading thifensulfuron-methyl was studied. The half-life for
      thifensulfuron-methyl was less than 6 days in liquid medium after addition ZWS16
      (5-400 mg thifensulfuron-methyl/l). Maximum biodegradation was 99.5 % for 50 mg
      thifensulfuron-methyl/l at 40  degrees C over 10 days. Of the five metabolites
      from the degradation of thifensulfuron-methyl that were identified, methyl 3-(N
      carbamoylsulfamoyl) thiophene-2-carboxylate and 3-[(formimidoylamino-hydroxy
      methyl)-sulfamoyl)-thiophene-2-carboxylic acid are reported for the first time.
      The degradation pathways might proceed via cleavage of the sulfonylurea bridge, O
      demethylation, de-esterification and cleavage of the triazine ring. The removal
      of thifensulfuron-methyl was 58 % after inoculation of strain ZWS16 into
      sterilized soil. Strain ZWS16 can also degrade nicosulfuron, tribenuron-methyl,
      pyrazosulfuron-ethyl, metsulfuron-methyl and triasulfuron. CONCLUSIONS: Addition
      of strain ZWS16 to both liquid medium and sterilized soil accelerated the
      degradation of thifensulfuron-methyl. Strain ZWS16 might therefore be useful in
      removing thifensulfuron-methyl contamination in water and soil.

PMID- 25773197
TI  - Biotransformation of sucrose into hexyl-alpha-D-glucopyranoside and 
      polyglucosides by whole cells of Microbacterium paraoxydans.
AB  - OBJECTIVE: To determine the transglycosylation activity of cell-bound enzymes
      from Microbacterium paraoxydans to catalyze the synthesis of hexyl-alpha-D
      glucoside (HG) and -polyglucosides using sucrose as a glycosyl donor. RESULTS:
      Maximum HG yield (14.8 %) was achieved at 0.96 water activity in 12 h with
      sucrose at 0.5 M with lyophilized cells (equivalent to 8 IU alpha-glucosidase
      activity). The synthesized alkyl-glucosides and-polyglucosides were characterized
      by ESI-MS. Structural elucidation of the main product (purified by solid phase
      chromatography) was done by HSQC (2D NMR) which was confirmed as 1-hexyl-alpha-D
      glucopyranoside. The synthesis was scaled up in a fed-batch reactor, with
      continuous feeding of whole cells every 6 h and a total yield of ~44 % was
      obtained for hexyl-glucoside and -polyglucosides under the optimized conditions.
      CONCLUSION: Synthesis of HG, hexyl di- and tri-glucosides has been achieved using
      a novel method.

PMID- 25773198
TI  - Transdifferentiation of bone marrow-derived mesenchymal stem cells into salivary
      gland-like cells using a novel culture method.
AB  - OBJECTIVES: To investigate the transdifferentiation of bone marrow-derived
      mesenchymal stem cells (BMSCs) into salivary gland-like cells via a novel culture
      method employing induction culture medium collected from salivary gland cells.
      RESULTS: Primary salivary gland cells were cultured, and after the first passage,
      the culture medium was collected for use as induction medium. BMSCs (passage 3)
      were cultured in either induction medium (induction group) or DMEM/F12 medium
      with 10 % (v/v) fetal bovine serum (control group) before seeding on three
      dimensional collagen/chitosan scaffolds and subcutaneous transplantation into
      nude mice. The in vitro and in vivo transdifferentiation of BMSCs into salivary
      gland-like cells was evaluated by immunocytochemical analysis of alpha-amylase
      and cytokeratin-8 (CK-8) expression. Salivary gland-like cells cultured using
      this novel method maintained excellent biostability and exhibited relatively
      stable expression of alpha-amylase and CK-8 in vitro and in vivo. CONCLUSION:
      This novel culture method is feasible for inducing the transdifferentiation of
      BMSCs into salivary gland-like cells.

PMID- 25773199
TI  - A comparison of whole cell directed evolution approaches in breeding of
      industrial strain of Saccharomyces cerevisiae.
AB  - OBJECTIVE: To reduce the fermentation cost in very high gravity fermentations of
      ethanol using Saccharomyces cerevisiae, whole cell directed evolution approaches
      were carried out. RESULTS: The methods used included cell ploidy manipulation,
      global transcription machinery engineering and genome shuffling. Ethanol
      production by the four methods was improved compared with the control. Notably,
      the ethanol yield of a strain constructed by genome shuffling was enhanced by up
      to 11 % more than the control reaching 120 g ethanol/l in 35 h using a very high
      gravity fermentation with 300 g glucose/l. CONCLUSION: Genome shuffling can
      create strains with improved fermentation characteristics in very high gravity
      fermentations.

PMID- 25773200
TI  - A rare cause of reversible ophthalmoplegia: tension pneumocephalus with brainstem
      compression.

PMID- 25773201
TI  - Combining tape stripping and non-invasive reflectance confocal microscopy : an in
      vivo model to study skin damage.
AB  - BACKGROUND: Evaluation of (immuno)histological and cell biological changes in
      damaged skin requires often an invasive skin biopsy, making in vivo models
      inappropriate to study skin damage. Reflectance confocal microscopy (RCM) might
      overcome this limitation. Therefore, we evaluated the use of a tape-stripping
      model in combination with RCM to provide morphological data on skin damage and
      recovery. METHODS: In 25 volunteers, a tape-stripping stimulus was applied. The
      skin was imaged with RCM during 1 week and 3 mm punch biopsies were obtained.
      RESULTS: Strong correlations between epidermal thickness determined by RCM and
      conventional histological measurements were found. RCM thickness measurements
      correlated well with epidermal proliferation. The 10* or 15* repeated tape
      stripping resulted in skin damage similar to acute stripping. Mild repeated tape
      stripping showed no skin damage. CONCLUSION: Overall, we demonstrated that non
      invasive RCM in combination with tape-stripping could be used as model to obtain
      morphological and cell biological data on skin-material interactions.

PMID- 25773202
TI  - Immunohistochemical and genetic profiles of endometrioid endometrial carcinoma
      arising from atrophic endometrium.
AB  - OBJECTIVE: Endometrial carcinomas are divided into type I endometrioid
      endometrial carcinomas (EECs), thought to arise from hyperplastic endometrium,
      and type II nonendometrioid endometrial carcinomas, thought to arise from
      atrophic endometrium. However, a minority (20%) of EECs have atrophic background
      endometrium, which was shown to be a marker of a worse prognosis. This study
      compares the immunohistochemical and genetic profiles of this possible third type
      to that of the known two types. METHODS: 43 patients with grade 1 EEC and
      hyperplastic background endometrium (type I), 43 patients with grade 1 EEC and
      atrophic background endometrium (type III) and 21 patients with serous carcinoma
      (type II) were included (n=107). Tissue microarrays of tumor samples were
      immunohistochemically stained for PTEN, L1CAM, ER, PR, p53, MLH1, PMS2, beta
      catenin, E-cadherin and MIB1. The BRAF, KRAS, and PIK3CA genes were analyzed for
      mutations. RESULTS: A significantly higher expression of ER and PR, and a lower
      expression of L1CAM, p53 and MLH1 were found in type I and III compared to type
      II carcinomas. Expression of E-cadherin was significantly reduced in type III
      compared to type I carcinomas. Mutation analysis showed significantly less
      mutations of KRAS in type III compared to type I and II carcinomas (p<0.01).
      CONCLUSION: There appear to be slight immunohistochemical and genetic differences
      between EECs with hyperplastic and atrophic background endometrium.
      Carcinogenesis of EEC in atrophic endometrium seems to be characterized by loss
      of E-cadherin and a lack of KRAS mutations. As expected, endometrioid and serous
      carcinomas were immunohistochemically different.

PMID- 25773203
TI  - Epithelioid trophoblastic tumor: A single institution case series at the New
      England Trophoblastic Disease Center.
AB  - OBJECTIVE: Epithelioid trophoblastic tumor (ETT) is a rare form of gestational
      trophoblastic neoplasm which is distinct based on its development from
      intermediate trophoblast cells and nodular growth pattern. The aim of this study
      is to describe a case series from a single institution with a review of the
      literature to better understand the clinical characteristics and outcomes for
      patients with ETT. METHODS: A retrospective review was performed using the IRB
      approved New England Trophoblastic Disease Center (NETDC) database from 1998 to
      2014. Eight patients were identified of which seven had complete records. Follow
      up data was obtained from the longitudinal medical records. RESULTS: Four (57.1%)
      patients presented with vaginal bleeding and two (28.6%) patients were
      asymptomatic at presentation. Three (42.9%) patients had extrauterine disease.
      All three patients with extrauterine disease who received chemotherapy had stable
      or progressive disease at follow-up. Only two (29%) patients who presented with
      non-metastatic disease and underwent hysterectomy were alive with no evidence of
      disease. The mean interval following antecedent pregnancy was 104months. All
      patients with an interval >4years demonstrated stable or progressive disease
      despite intensive chemotherapy. Two patients with non-metastatic disease who
      declined hysterectomy developed stable or progressive disease despite
      chemotherapy. CONCLUSIONS: This series highlights several features of ETT
      including the potential for asymptomatic presentation of extrauterine disease.
      The series also demonstrates chemoresistance, even with multi-agent therapy and a
      poor prognosis with extrauterine disease and an interval greater than 4years
      following the antecedent pregnancy suggesting that surgery remains critical in
      disease control.

PMID- 25773205
TI  - Erratum to: Lmo0171, a novel internalin-like protein, determines cell morphology
      of Listeria monocytogenes and its ability to invade human cell lines.

PMID- 25773204
TI  - The Caulobacter crescentus transducing phage Cr30 is a unique member of the T4
      like family of myophages.
AB  - Bacteriophage Cr30 has proven useful for the transduction of Caulobacter
      crescentus. Nucleotide sequencing of Cr30 DNA revealed that the Cr30 genome
      consists of 155,997 bp of DNA that codes for 287 proteins and five tRNAs. In
      contrast to the 67 % GC content of the host genome, the GC content of the Cr30
      genome is only 38 %. This lower GC content causes both the codon usage pattern
      and the amino acid composition of the Cr30 proteins to be quite different from
      those of the host bacteria. As a consequence, the Cr30 mRNAs probably are
      translated at a rate that is slower than the normal rate for host mRNAs. A
      phylogenetic comparison of the genome indicates that Cr30 is a member of the T4
      like family that is most closely related to a new group of T-like phages
      exemplified by fM12.

PMID- 25773206
TI  - Lung cancer diagnosis: when speed wins the day.

PMID- 25773207
TI  - Triage tests: a new priority for tuberculosis diagnostics.

PMID- 25773208
TI  - Treatment of pulmonary disease caused by non-tuberculous mycobacteria.

PMID- 25773209
TI  - Eric Goosby: the UN special envoy for tuberculosis.

PMID- 25773210
TI  - Leon Charles Albert Calmette and Jean-Marie Camille Guerin.

PMID- 25773211
TI  - Indigenous Australians and the struggle for health equality.

PMID- 25773212
TI  - Tuberculosis treatment and management--an update on treatment regimens, trials,
      new drugs, and adjunct therapies.
AB  - WHO estimates that 9 million people developed active tuberculosis in 2013 and 1.5
      million people died from it. Multidrug-resistant (MDR) and extensively drug
      resistant (XDR) tuberculosis continue to spread worldwide with an estimated
      480,000 new cases in 2013. Treatment success rates of MDR and XDR tuberculosis
      are still low and development of new, more effective tuberculosis drugs and
      adjunct therapies to improve treatment outcomes are urgently needed. Although
      standard therapy for drug-sensitive tuberculosis is highly effective, shorter,
      more effective treatment regimens are needed to reduce the burden of infectious
      cases. We review the latest WHO guidelines and global recommendations for
      treatment and management of drug-sensitive and drug-resistant tuberculosis, and
      provide an update on new drug development, results of several phase 2 and phase 3
      tuberculosis treatment trials, and other emerging adjunct therapeutic options for
      MDR and XDR tuberculosis. The use of fluoroquinolone-containing (moxifloxacin and
      gatifloxacin) regimens have failed to shorten duration of therapy, and the new
      tuberculosis drug pipeline is sparse. Scale-up of existing interventions with
      increased investments into tuberculosis health services, development of new
      antituberculosis drugs, adjunct therapies and vaccines, coupled with visionary
      political leadership, are still our best chance to change the unacceptable status
      quo of the tuberculosis situation worldwide and the growing problem of drug
      resistant tuberculosis.

PMID- 25773213
TI  - Non-tuberculous mycobacteria in children: muddying the waters of tuberculosis
      diagnosis.
AB  - Non-tuberculous mycobacteria (NTM) are a large family of acid-fast bacteria,
      widespread in the environment. In children, NTM cause lymphadenitis, skin and
      soft tissue infections, and occasionally also lung disease and disseminated
      infections. These manifestations can be indistinguishable from tuberculosis on
      the basis of clinical and radiological findings and tuberculin skin testing. A
      diagnostic and therapeutic problem for respiratory physicians and other
      clinicians is therefore evident, particularly in settings where childhood
      tuberculosis is common, and bacteriological confirmation of any mycobacterial
      disease is difficult because of low availability of laboratory services in low
      resource settings and the inherent paucibacillary nature of mycobacterial disease
      in childhood. The epidemiology of NTM varies by world region, and attempts to
      understand the burden of NTM disease and to identify risk factors in the
      paediatric population are hampered by inadequate mandatory NTM reporting and the
      overlap of clinical presentation with tuberculosis. The immune response to both
      NTM and Mycobacterium tuberculosis is based on cellular immunity and relies on
      the type-1 cytokine pathway. The disruption of this immune response by genetic or
      acquired mechanisms, such as mendelian susceptibility to mycobacterial disease or
      HIV, might result in predisposition to mycobacterial infections. Published
      diagnostic and management guidelines do not provide specific advice for diagnosis
      of NTM in children, from whom the quantity and quality of diagnostic samples are
      often suboptimum. Treatment of NTM infections is very different from the
      treatment of tuberculosis, depends on the strain and anatomical site of
      infection, and often involves antibiotic combinations, surgery, or both. In this
      Review, we summarise the epidemiological and clinical features of NTM infection
      in children, with a specific focus on the implications for public health in
      settings with a high endemic burden of childhood tuberculosis. 

PMID- 25773214
TI  - Antibiotic trials for community-acquired pneumonia.

PMID- 25773215
TI  - Antibiotic trials for community-acquired pneumonia--authors' reply.

PMID- 25773216
TI  - Interpreting internet-based trials: StopAdvisor for smoking cessation.

PMID- 25773217
TI  - Interpreting internet-based trials: StopAdvisor for smoking cessation--authors'
      reply.

PMID- 25773218
TI  - Neuraminidase inhibitors for influenza: fully evaluating benefits and harms.

PMID- 25773219
TI  - Responding to the Syrian health crisis: the need for data and research.

PMID- 25773220
TI  - Intravesical therapy for bladder cancer.
AB  - INTRODUCTION: Transurethral resection of bladder tumor (TURBT) is the gold
      standard initial diagnostic intervention for bladder cancer and provides
      diagnostic, therapeutic and prognostic benefit in non-muscle-invasive bladder
      cancer (NMIBC). However, TURBT alone is inadequate for optimal management of
      NMIBC, as patients will experience recurrence or progression depending on tumor
      characteristics. Adjuvant intravesical therapy with either immunotherapy or
      chemotherapy has been shown to reduce recurrence and/or progression in
      appropriately selected patients through immunostimulation or direct cell
      ablation. AREAS COVERED: This review will discuss risk stratification of patients
      with NMIBC and role of intravesical therapies in reducing recurrence and
      progression of disease in these patients. A Medline search was performed to
      identify the best available evidence available from various systematic reviews,
      meta-analyses, and clinical trials on various immunotherapy and chemotherapy
      agents. In addition, the main aspects of drug pharmacology (mechanism of action,
      dosing and administration) and side effects will be reviewed. EXPERT OPINION: The
      selection of the appropriate intravesical agent for NMIBC is complex and is
      dependent on risk stratification and intravesical agent toxicity. Intravesical
      induction and maintenance immunotherapy with Bacillus Calmette-Guerin (BCG) is
      the preferred and most effective agent for patients with high-risk NMIBC
      (carcinoma in situ and high-grade disease) and reduces both recurrence and
      progression.

PMID- 25773221
TI  - Neuronal hyperactivity--A key defect in Alzheimer's disease?
AB  - Traditionally, the impairment of cognitive functions in Alzheimer's disease (AD)
      is thought to result from a reduction in neuronal and synaptic activities, and
      ultimately cell death. Here, we review recent in vivo evidence from mouse models
      and human patients indicating that, particularly in early stages of AD, neuronal
      circuits are hyperactive instead of hypoactive. Functional analyses at many
      levels, from single neurons to neuronal populations to large-scale networks, with
      a variety of electrophysiological and imaging techniques have revealed two forms
      of AD-related hyperactivity and provided first insights into the synaptic
      mechanisms. The unexpected finding that hyperactivity is an early neuronal
      dysfunction represents a major conceptual shift in our understanding of AD that
      may have important implications for the development of therapeutic approaches.

PMID- 25773222
TI  - Life course epidemiology of trauma and related psychopathology in civilian
      populations.
AB  - Traumatic events are ubiquitous exposures that interact with life course events
      to increase risk of acute psychopathology and alter mental health trajectories.
      While the majority of persons exposed to trauma experience mild to moderate
      psychological distress followed by a return to pre-trauma health, many persons
      exposed to trauma experience substantial distress that lasts for several years.
      Therefore, in an effort to understand why exposure to trauma can provoke such a
      range of reactions, we apply a life course approach that considers the complex
      accumulation and interaction of life experiences that range from social to
      biological factors, which occur over the life span-from gestation to death and
      across generations. We present this evidence in three categories: genetics and
      biology, individual exposures, and community experiences, followed by discussing
      challenges in existing research and directions for future study. 

PMID- 25773223
TI  - Assessment of problematic sexual interests with the penile plethysmograph: an
      overview of assessment laboratories.
AB  - Phallometric testing, or penile plethysmography (PPG), is an objective measure of
      sexual arousal for males. While extensive research on the reliability and
      validity of PPG has promoted its reputation as the "gold standard" of objective
      measurement of sexual arousal, there is a lack of standardization of stimulus
      sets and interpretation of results between sites. This article describes the
      laboratory protocol employed for PPG at the Royal Ottawa Mental Health Centre's
      Sexual Behaviours Clinic (SBC) in Ottawa, Ontario, as well as those used by the
      Sexual Behaviors Clinic and Lab (SBCL) in the Community and Public Safety
      Psychiatry Division (CPSPD) of the Department of Psychiatry and Behavioral
      Sciences at Medical University of South Carolina (MUSC) in Charleston, South
      Carolina. The need for standardization in both testing protocol and stimuli use
      across sites are highlighted. 

PMID- 25773224
TI  - Ophthalmology issues in schizophrenia.
AB  - Schizophrenia is a complex mental disorder associated with not only cognitive
      dysfunctions, such as memory and attention deficits, but also changes in basic
      sensory processing. Although most studies on schizophrenia have focused on
      disturbances in higher-order brain functions associated with the prefrontal
      cortex or frontal cortex, recent investigations have also reported abnormalities
      in low-level sensory processes, such as the visual system. At very early stages
      of the disease, schizophrenia patients frequently describe in detail symptoms of
      a disturbance in various aspects of visual perception that may lead to worse
      clinical symptoms and decrease in quality of life. Therefore, the aim of this
      review is to describe the various studies that have explored the visual issues in
      schizophrenia. 

PMID- 25773225
TI  - Neurology issues in schizophrenia.
AB  - Schizophrenia ranks among the leading causes of disability worldwide. The
      presence of neurological signs co-occurring with the psychiatric symptoms is
      indicative of an organic brain pathology. In the present article, we review the
      current literature on neurology issues in schizophrenia. Firstly, common
      neurological signs found in patients with schizophrenia (neurological soft signs
      and smell abnormalities) and their association with imaging findings are
      reviewed. Secondly, the significant association of schizophrenia with epilepsy
      and stroke is described as well as the absent association with other organic
      brain diseases such as multiple sclerosis. Thirdly, we discuss the potential role
      of NMDA receptor antibodies in schizophrenia. Fourthly, neurological side effects
      of antipsychotic drugs and their treatment are reviewed; and lastly, we discuss
      neurocognitive deficits in patients with schizophrenia and their treatment. The
      focus of the review remains on articles with relevance to the clinician. 

PMID- 25773226
TI  - Application of the Research Domain Criteria (RDoC) framework to eating disorders:
      emerging concepts and research.
AB  - The Research Domain Criteria (RDoC) project was initiated by the National
      Institute of Mental Health as a heuristic for addressing the limitations of
      categorical, symptom-based psychiatric diagnoses. RDoC is conceptualized as a
      matrix, with the rows representing dimensional constructs or domains implicated
      in the expression of psychiatric symptoms and the columns representing units of
      analysis that can be used to assess dimensional constructs (i.e., genes,
      molecules, cells, circuits, physiology, behavior, and self-reports). Few studies
      in eating disorders have adopted an RDoC framework, but accumulating data provide
      support for the relevance of RDoC dimensions to eating disorder symptoms. Herein,
      we review findings from RDoC-informed studies across the five domains of
      functioning included in the RDoC matrix-negative valence systems, positive
      valence systems, cognitive systems, systems for social processes, and arousal and
      regulatory systems-and describe directions for future research utilizing RDoC to
      enhance study design and treatment development in eating disorders. 

PMID- 25773228
TI  - Evolutionary allometry of the thoracolumbar centra in felids and bovids.
AB  - Mammals have evolved a remarkable range of body sizes, yet their overall body
      plan remains unaltered. One challenge of evolutionary biology is to understand
      the mechanisms by which this size diversity is achieved, and how the mechanical
      challenges associated with changing body size are overcome. Despite the
      importance of the axial skeleton in body support and locomotion, and much
      interest in the allometry of the appendicular skeleton, little is known about
      vertebral allometry outside primates. This study compares evolutionary allometry
      of the thoracolumbar centra in two families of quadrupedal running mammals:
      Felidae and Bovidae. I test the hypothesis that, as size increases, the
      thoracolumbar region will resist increasing loads by becoming a) craniocaudally
      shorter, and b) larger in cross-sectional area, particularly in the sagittal
      plane. Length, width, and height of the thoracolumbar centra of 23 felid and 34
      bovid species were taken. Thoracic, prediaphragmatic, lumbar, and
      postdiaphragmatic lengths were calculated, and diameters were compared at three
      equivalent positions: the midthoracic, the diaphragmatic and the midlumbar
      vertebra. Allometric slopes were calculated using a reduced major axis
      regression, on both raw and independent contrasts data. Slopes and elevations
      were compared using an ANCOVA. As size increases the thoracolumbar centra become
      more robust, showing preferential reinforcement in the sagittal plane. There was
      less allometric shortening of the thoracic than the lumbar region, perhaps
      reflecting constraints due to its connection with the respiratory apparatus. The
      thoracic region was more robust in bovids than felids, whereas the lumbar region
      was longer and more robust in felids than bovids. Elongation of lumbar centra
      increases the outlever of sagittal bending at intervertebral joints, increasing
      the total pelvic displacement during dorsomobile running. Both locomotor
      specializations and functional regionalization of the axial skeleton appear to
      have influenced its response to increasing size.

PMID- 25773227
TI  - Gastroenterology issues in schizophrenia: why the gut matters.
AB  - Genetic and environmental studies implicate immune pathologies in schizophrenia.
      The body's largest immune organ is the gastrointestinal (GI) tract. Historical
      associations of GI conditions with mental illnesses predate the introduction of
      antipsychotics. Current studies of antipsychotic-naive patients support that gut
      dysfunction may be inherent to the schizophrenia disease process. Risk factors
      for schizophrenia (inflammation, food intolerances, Toxoplasma gondii exposure,
      cellular barrier defects) are part of biological pathways that intersect those
      operant in the gut. Central to GI function is a homeostatic microbial community,
      and early reports show that it is disrupted in schizophrenia. Bioactive and toxic
      products derived from digestion and microbial dysbiosis activate adaptive and
      innate immunity. Complement C1q, a brain-active systemic immune component,
      interacts with gut-related schizophrenia risk factors in clinical and
      experimental animal models. With accumulating evidence supporting newly
      discovered gut-brain physiological pathways, treatments to ameliorate brain
      symptoms of schizophrenia should be supplemented with therapies to correct GI
      dysfunction. 

PMID- 25773229
TI  - Nanoprecipitation of polymeric nanoparticle micelles based on 2
      methacryloyloxyethyl phosphorylcholine (MPC) with 2-(diisopropylamino)ethyl
      methacrylate (DPA), for intracellular delivery applications.
AB  - Biodistribution of nanoparticle-based intracellular delivery systems is mediated
      primarily by particle size and physicochemical properties. As such, overcoming
      the rapid removal of these by the reticuloendothelial system remains a
      significant challenge. To date, a number of copolymer nanoparticle systems based
      on 2-methacryloyloxyethyl phosphorylcholine (MPC) with 2-(diisopropylamino)ethyl
      methacrylate (DPA), displaying biomimetic and pH responsive properties, have been
      published, however these have been predominately polymersome based, whilst
      micelle systems have remained relatively unexplored. This study utilised
      nanoprecipitation to investigate the effects of solvent and buffer choice upon
      micelle size and polydispersity, and found using methanol produced monodisperse
      micelles of circa 70 nm diameter, whilst ethanol produced polydisperse systems
      with nanoparticles of circa 128 nm diameter. The choice of aqueous buffer,
      dialysis of the systems, extended storage, and exposure to a wide temperature
      range (5-70  degrees C) had no significant effect on micelle size, and the
      systems were highly resistant to dilution, indicating excellent colloidal
      stability. Optimisation of the nanoprecipitation process, post precipitation, was
      investigated, and model drugs successfully loaded whilst maintaining system
      stability. Subsequent in vitro studies suggested that the micelles were of
      negligible cellular toxicity, and an apparent cellular uptake was observed via
      confocal laser scanning microscopy. This paper presents the first report of an
      optimised nanoprecipitation methodology for the formation of MPC-DPA nanoparticle
      micelles, and in doing so achieved monodisperse systems with the size and
      physicochemical characteristics seen as desirable for long circulating
      therapeutic delivery vehicles.

PMID- 25773230
TI  - Fabrication of gelatin-strontium substituted calcium phosphate scaffolds with
      unidirectional pores for bone tissue engineering.
AB  - This study fabricated homogeneous gelatin-strontium substituted calcium phosphate
      composites via coprecipitation in a gelatin solution. Unidirectional porous
      scaffolds with an oriented microtubular structure were then manufactured using
      freeze-drying technology. The resulting structure and pore alignment were
      determined using scanning electron microscopy. The pore size were in the range of
      200-400 MUm, which is considered ideal for the engineering of bone tissue. The
      scaffolds were further characterized using energy dispersive spectroscopy,
      Fourier transform infrared spectroscopy, and X-ray diffraction. Hydroxyapatite
      was the main calcium phosphate compound in the scaffolds, with strontium
      incorporated into the crystal structure. The porosity of the scaffolds decreased
      with increasing concentration of calcium-phosphate. The compressive strength in
      the longitudinal direction was two to threefold higher than that observed in the
      transverse direction. Our results demonstrate that the composite scaffolds
      degraded by approximately 20 % after 5 weeks. Additionally, in vitro results
      reveal that the addition of strontium significantly increased human osteoblastic
      cells proliferation. Scaffolds containing strontium with a Sr-CaP/(gelatin + Sr
      CaP) ratio of 50 % provided the most suitable environment for cell proliferation,
      particularly under dynamic culture conditions. This study demonstrates the
      considerable potential of composite scaffolds composed of gelatin-strontium
      substituted calcium phosphate for applications in bone tissue engineering.

PMID- 25773231
TI  - Pluronic F-127 hydrogel as a promising scaffold for encapsulation of dental
      derived mesenchymal stem cells.
AB  - Dental-derived mesenchymal stem cells (MSCs) provide an advantageous therapeutic
      option for tissue engineering due to their high accessibility and
      bioavailability. However, delivering MSCs to defect sites while maintaining a
      high MSC survival rate is still a critical challenge in MSC-mediated tissue
      regeneration. Here, we tested the osteogenic and adipogenic differentiation
      capacity of dental pulp stem cells (DPSCs) in a thermoreversible Pluronic F127
      hydrogel scaffold encapsulation system in vitro. DPSCs were encapsulated in
      Pluronic ((r)) F-127 hydrogel and stem cell viability, proliferation and
      differentiation into adipogenic and osteogenic tissues were evaluated. The
      degradation profile and swelling kinetics of the hydrogel were also analyzed. Our
      results confirmed that Pluronic F-127 is a promising and non-toxic scaffold for
      encapsulation of DPSCs as well as control human bone marrow MSCs (hBMMSCs),
      yielding high stem cell viability and proliferation. Moreover, after 2 weeks of
      differentiation in vitro, DPSCs as well as hBMMSCs exhibited high levels of mRNA
      expression for osteogenic and adipogenic gene markers via PCR analysis. Our
      histochemical staining further confirmed the ability of Pluronic F-127 to direct
      the differentiation of these stem cells into osteogenic and adipogenic tissues.
      Furthermore, our results revealed that Pluronic F-127 has a dense tubular and
      reticular network morphology, which contributes to its high permeability and
      solubility, consistent with its high degradability in the tested conditions.
      Altogether, our findings demonstrate that Pluronic F-127 is a promising scaffold
      for encapsulation of DPSCs and can be considered for cell delivery purposes in
      tissue engineering.

PMID- 25773232
TI  - A glass polyalkenoate cement carrier for bone morphogenetic proteins.
AB  - This work considers a glass polyalkenoate cement (GPC)-based carrier for the
      effective delivery of bone morphogenetic proteins (BMPs) at an implantation site.
      A 0.12 CaO-0.04 SrO-0.36 ZnO-0.48 SiO2 based glass and poly(acrylic acid) (PAA,
      Mw 213,000) were employed for the fabrication of the GPC. The media used for the
      water source in the GPC reaction was altered to produce a series of GPCs. The GPC
      liquid media was either 100 % distilled water with additions of albumin at 0, 2,
      5 and 8 wt% of the glass content, 100 % formulation buffer (IFB), and 100 % BMP
      (150 ug rhBMP-2/ml IFB). Rheological properties, compressive strength, ion
      release profiles and BMP release were evaluated. Working times (Tw) of the
      formulated GPCs significantly increased with the addition of 2 % albumin and
      remained constant with further increases in albumin content or IFB solutions.
      Setting time (Ts) experienced an increase with 2 and 5 % albumin content, but a
      decrease with 8 % albumin. Changing the liquid source to IFB containing 5 %
      albumin had no significant effect on Ts compared to the 8 % albumin-containing
      BT101. Replacing the albumin with IFB/BMP-2 did not significantly affect Tw.
      However, Ts increased for the BT101_BMP-2 containing GPCs, compared to all other
      samples. The compressive strength evaluated 1 day post cement mixing was not
      affected significantly by the incorporation of BMPs, but the ion release did
      increase from the cements, particularly for Zn and Sr. The GPCs released BMP
      after the first day, which decreased in content during the following 6 days. This
      study has proven that BMPs can be immobilized into GPCs and may result in novel
      materials for clinical applications.

PMID- 25773234
TI  - Insulin biosimilars: the impact on rapid-acting analogue-based therapy.
AB  - The impending expiration of patent protection for recombinant insulins provides
      the opportunity to introduce cost-saving copies, named biosimilars, onto the
      market. Although there is broad experience in the production and characterisation
      of insulins, the development of copies is still a challenge. In this paper, the
      main features of insulins and the EU regulatory framework for their biosimilar
      products are reviewed. The main focus is on rapid-acting insulin analogues
      (Humalog((r)); Novolog((r))/NovoRapid((r)); Apidra((r))). Since they differ by
      one or two amino acids in chain B, production of one biosimilar for all three
      drug products is not feasible. However, from post-marketing-collected clinical
      data, rapid-acting insulin analogues seem to have similar therapeutic efficacy.
      It is reasonable to suppose that, for prescription to treatment-naive patients,
      the cheaper biosimilar would be the preferred choice of physicians, either
      spontaneously or induced by health insurance. Therefore, its introduction will
      affect the market share of all the other rapid-acting insulin analogues. 

PMID- 25773233
TI  - The impact of human immunodeficiency virus infection on obstetric hemorrhage and
      blood transfusion in South Africa.
AB  - BACKGROUND: Globally, as in South Africa, obstetric hemorrhage (OH) remains a
      leading cause of maternal mortality and morbidity. Although blood transfusion is
      critical to OH management, the incidence and predictors of transfusion as well as
      their relation to human immunodeficiency virus (HIV) infection are poorly
      described. STUDY DESIGN AND METHODS: A cross-sectional study was conducted of all
      peripartum patients at four major hospitals in South Africa (April to July 2012).
      Comprehensive clinical data were collected on patients who sustained OH and/or
      were transfused. Logistic regression was used to model risk factors for OH and
      transfusion. RESULTS: A total of 15,725 peripartum women were evaluated, of whom
      3969 (25.2%) were HIV positive. Overall, 387 (2.5%) women sustained OH and 438
      (2.8%) received transfusions, including 213 (1.4%) women with both OH and
      transfusion. There was no significant difference in OH incidence between HIV
      positive (2.8%) and HIV-negative (2.3%) patients (adjusted odds ratio [OR], 0.95;
      95% confidence interval [CI], 0.72-1.25). In contrast, the incidence of blood
      transfusion was significantly higher in HIV-positive (3.7%) than in HIV-negative
      (2.4%) patients (adjusted OR, 1.52; 95% CI, 1.14-2.03). Other risk factors for
      transfusion included OH, low prenatal hemoglobin, the treating hospital, lack of
      prenatal care, and gestational age of not more than 34 weeks. CONCLUSION: In the
      South African obstetric setting, the incidence of peripartum blood transfusion is
      significantly higher than in the United States and other high-income countries
      while OH incidence is similar. While OH and prenatal anemia are major predictors
      of transfusion, HIV infection is a common and independent contributing factor.

PMID- 25773235
TI  - Governance, guidelines, audit, and revalidation in the 21st century.

PMID- 25773236
TI  - Total synthesis of schilancitrilactones b and C.
AB  - The first total syntheses of schilancitrilactones B and C have been accomplished
      in 17 steps (longest linear sequence) from commercially available materials. Key
      steps include an intramolecular radical cyclization to provide the seven-membered
      ring, late-stage iodination, and an intermolecular radical addition reaction to
      complete the total synthesis. 

PMID- 25773237
TI  - Discussion of "On Bayesian Estimation of Marginal Structural Models".

PMID- 25773238
TI  - A practical approach to calculate the time evolutions of magnetic field effects
      on photochemical reactions in nano-structured materials.
AB  - A practical method to calculate time evolutions of magnetic field effects (MFEs)
      on photochemical reactions involving radical pairs is developed on the basis of
      the theory of the chemically induced dynamic spin polarization proposed by
      Pedersen and Freed. In theory, the stochastic Liouville equation (SLE), including
      the spin Hamiltonian, diffusion motions of the radical pair, chemical reactions,
      and spin relaxations, is solved by using the Laplace and the inverse Laplace
      transformation technique. In our practical approach, time evolutions of the MFEs
      are successfully calculated by applying the Miller-Guy method instead of the
      final value theorem to the inverse Laplace transformation process. Especially,
      the SLE calculations are completed in a short time when the radical pair dynamics
      can be described by the chemical kinetics consisting of diffusions, reactions and
      spin relaxations. The SLE analysis with a short calculation time enables one to
      examine the various parameter sets for fitting the experimental date. Our study
      demonstrates that simultaneous fitting of the time evolution of the MFE and of
      the magnetic field dependence of the MFE provides valuable information on the
      diffusion motions of the radical pairs in nano-structured materials such as
      micelles where the lifetimes of radical pairs are longer than hundreds of nano
      seconds and the magnetic field dependence of the spin relaxations play a major
      role for the generation of the MFE. 

PMID- 25773239
TI  - Changes in feeding and drinking motivations and glucose content in male rats
      after single or chronic administration of obestatin or its fragment (1-4).

PMID- 25773240
TI  - Identification of the muscarinic receptor subtypes involved in autoregulation of
      acetylcholine quantal release from frog motor nerve endings.

PMID- 25773241
TI  - Evaluation of the length constant in the atrial myocardium and pulmonary vein
      myocardium in mammals.

PMID- 25773242
TI  - The effect of histidine on the contractility and adrenoreactivity of the
      myocardium of nonpregnant and pregnant rats.

PMID- 25773243
TI  - "Provocation test" as a novel approach to early diagnosis of Parkinson's disease.

PMID- 25773244
TI  - Patterns of lateral wear facets on molar teeth of voles (Arvicolinae).

PMID- 25773245
TI  - First record of Mylagaulid rodents (Rodentia, Mammalia) from the Miocene of
      Eastern Siberia (Olkhon Island, Baikal Lake, Irkutsk Region, Russia).
AB  - A new genus and species of rodent, Lamugaulus olkhonensis, belonging to the
      subfamily Promylagaulinae of the family Mylagaulidae, is described on the basis
      of isolated teeth from the Khalagay Formation of the Lower Miocene Tagay locality
      (Olkhon island, Lake Baikal, Irkutsk Region). This is the first record of
      mylagaulids in Eastern Siberia, significantly expanding the data on the
      distribution of this mainly North American group of rodents in Asia and showing
      its presence outside the Central Asian arid zone. 

PMID- 25773246
TI  - Evaluation of cytogenetic abnormalities in cells of submerged plant Elodea
      canadensis in the Yenisei River section affected by industrial pollution: Field
      studies and laboratory experiments.

PMID- 25773247
TI  - A finding of the male mammoth carcass in the Karginsky suit of the Upper
      Pleistocene of the Taimyr Peninsula.

PMID- 25773248
TI  - The size, but not the fluctuating asymmetry of the leaf, of silver birch changes
      under the gradient influence of emissions of the Karabash Copper Smelter Plant.

PMID- 25773249
TI  - The limitation of carbon sink in Western Siberian forest ecosystems.

PMID- 25773250
TI  - Multimode phenomenon in the population dynamics of animals with short live
      cycles.

PMID- 25773251
TI  - Fossil fur as a new source of information on the Ice Age biota.

PMID- 25773252
TI  - Selection of mice for high scores of elementary logical task solution.

PMID- 25773253
TI  - Palaeoecological and palaeoclimatical reconstructions of Holocene according
      chironomid analysis of Lake Glubokoye sediments.

PMID- 25773254
TI  - Role of human pregnancy-specific beta1-glycoprotein in the regulation of
      immunological tolerance-associated factors.

PMID- 25773255
TI  - Role of gap junctions and mechanosensitive ion channels in the mechanisms of
      growth pulsations of Gonothyraea loveni.

PMID- 25773257
TI  - Celastrol Ameliorates EAE Induction by Suppressing Pathogenic T Cell Responses in
      the Peripheral and Central Nervous Systems.
AB  - Multiple sclerosis (MS) is the prototypical inflammatory demyelinating disease of
      the central nervous system (CNS), and MS results in physical and cognitive
      impairments, such as fatigue, pain, depression and bladder dysfunction. Though
      many therapies for MS have been developed, the safety profile and effectiveness
      of these therapies still need to be defined. Thus, new therapies for MS must be
      explored. Celastrol, a quinonemethide triterpene, is a pharmacologically active
      compound present in Thunder God Vine root extracts used to treat inflammatory and
      autoimmune diseases. Molecular studies have identified several molecular targets,
      which are mostly centered on the inhibition of IKK-NF-kappaB signaling. The
      animal model of experimental autoimmune encephalomyelitis (EAE) has been widely
      used in MS studies; thus, we tried to explore the role of celastrol in EAE
      development in this study. We demonstrated that the intraperitoneal injection of
      celastrol significantly attenuated EAE disease. Th17 cell responses in the
      peripheral lymph nodes in EAE mice were also inhibited by celastrol. We
      determined that celastroldownregulated cytokine production in bone-marrow derived
      dendritic cells (BMDCs). Accordingly, T cells that were co-cultured with either
      BMDCs pre-treated with celastrolor splenic DCs and then collected on day 7 after
      EAE immunizationshowed that Th17 cell polarization is suppressed in the above two
      situations. Moreover, celastrol was required for tissue-infiltrating DCs to
      sustain Th17 responses in the central nervous system (CNS). Taken together, the
      results of our study demonstrate that celastrol ameliorates EAE development by
      suppressing pathogenic Th17 responses; this finding offers a better understanding
      of the role of celastrol in EAE development as well as new proposals for clinical
      interventions. 

PMID- 25773258
TI  - Agreement between whole blood and plasma sodium measurements in profound
      hyponatremia.
AB  - OBJECTIVES: We compared two different methods of whole blood sodium measurement
      to plasma sodium measurement using samples in the profoundly hyponatremic range
      (Na < 120 mmol/L). DESIGN AND METHODS: Whole blood pools with a range of low
      sodium values were generated using combinations and dilutions of pooled
      electrolyte-balanced lithium heparin samples submitted for arterial blood gas
      analysis. Each pool was analyzed five times on a Radiometer 827 blood gas
      analyzer and iSTAT analyzer. Pools were centrifuged to produce plasma, which was
      analyzed five times on a Roche Cobas c501 chemistry analyzer. An additional 40
      fresh (analyzed on day of collection) excess lithium heparin arterial blood gas
      samples from 36 patients were analyzed on the Radiometer 827, iSTAT, and Cobas
      c501 as described above. The setting was a tertiary referral center. Blood
      samples were collected from a combination of patients in the intensive care unit,
      operating theaters and emergency room. RESULTS: All methods demonstrated
      excellent precision, even in the profoundly hyponatremic measurement range (Na <
      120 mmol/L using a plasma reference method). However, agreement between the
      methods varied with the degree of hyponatremia. In the profoundly hyponatremic
      range, Radiometer whole blood sodium values were nearly identical to plasma
      reference sodium, while iSTAT whole blood sodium showed a consistent positive
      bias relative to plasma sodium in this range. CONCLUSION: If whole blood direct
      sodium measurements are compared with plasma sodium in profoundly hyponatremic
      patients consideration should be given to the use of Radiometer blood gas
      analyzers over iSTAT since the latter shows a positive bias relative to a plasma
      comparative method.

PMID- 25773259
TI  - Comparison of results from commercial assays for plasma CTX: The need for
      harmonization.
AB  - INTRODUCTION: Plasma C-terminal telopeptide of type I collagen (CTX) is the
      nominated reference bone resorption marker. We set out to test the agreement of
      patients' results between the available plasma CTX assays. METHODS: Samples were
      collected from patients attending tertiary hospitals and clinics for
      investigation and management of metabolic bone disease. Plasma (EDTA) samples
      were collected from fasted patients between 7.00 am and 11.00 am, divided into
      three portions and stored at -20 degrees C until analysis. Plasma CTX was
      measured by enzyme-linked immunosorbent assay (ELISA) (Immunodiagnostic Systems
      plc), E170 (Roche Diagnostics) and IDS-iSYS (Immunodiagnostic Systems plc)
      methods. Agreement of patient sample results was assessed by Passing and Bablok
      regression. Commutability of the calibrators in each kit was assessed by assaying
      each calibrator in the alternate methods and comparing the observed results with
      those expected based on the relevant patients' samples method comparison; +/-8.1%
      was set as the criterion for commutablity. RESULTS: 161 specimens were analysed.
      Regression parameters (slope, intercept) were 0.788, 0.2 ng/L for Roche vs ELISA,
      1.266 and -109 ng/L for iSYS vs ELISA and 1.605 and -109 ng/L for iSYS vs Roche.
      Only the ELISA calibrator assayed in the Roche assay gave a result within 8.1% of
      the expected value. CONCLUSIONS: There is significant disagreement between the
      results generated for patient samples by the 3 CTX assays and limited
      commutability of the currently supplied calibrator materials between assays.
      Harmonization of the results from the different assays would greatly enhance the
      value of CTX as the reference bone resorption marker.

PMID- 25773261
TI  - Erratum to: The protective effect of epoxyeicosatrienoic acids on cerebral
      ischemia/reperfusion injury is associated with PI3K/Akt pathway and ATP-sensitive
      potassium channels.

PMID- 25773260
TI  - Tacrolimus to Belatacept Conversion Following Hand Transplantation: A Case
      Report.
AB  - Vascularized composite allotransplantation (VCA) has emerged as a viable limb
      replacement strategy for selected patients with upper limb amputation. However,
      allograft rejection has been seen in essentially all reported VCA recipients
      indicating a requirement for substantial immunosuppressive therapy. Calcineurin
      inhibitors have served as the centerpiece agent in all reported cases, and CNI
      associated complications associated with the broad therapeutic effects and side
      effects of calcineurin inhibitors have been similarly common. Recently,
      belatacept has been approved as a calcineurin inhibitor replacement in kidney
      transplantation, but to date, its use in VCA has not been reported. Herein, we
      report on the case of a hand transplant recipient who developed recurrent acute
      rejection with alloantibody formation and concomitant calcineurin inhibitor
      nephrotoxicity, all of which resolved upon conversion from a maintenance regimen
      of tacrolimus, mycophenolate mofetil and steroids to belatacept and sirolimus.
      This case indicates that belatacept may be a reasonable maintenance
      immunosuppressive alternative for use in VCA, providing sufficient prophylaxis
      from rejection with a reduced side effect profile, the latter being particularly
      relevant for nonlife threatening conditions typically treated by VCA. 

PMID- 25773262
TI  - Salsolinol Damaged Neuroblastoma SH-SY5Y Cells Induce Proliferation of Human
      Monocyte THP-1 Cells Through the mTOR Pathway in a Co-culture System.
AB  - Despite extensive efforts to study the inflammatory process in the central
      nervous system of Parkinson's disease (PD) patients, little is known about the
      role of peripheral blood mononuclear cells (PBMCs) in PD. In the present study,
      we used an in vitro co-culture system to study the role of the human monocyte
      cell line THP-1 in medium conditioned by the neuroblastoma cell line SH-SY5Y
      damaged with the endogenous neurotoxin 1-methyl-4-phenyl-1,2,3,4
      tetrahydroisoquinoline (Salsolinol, Sal) in co-culture with the human glioma cell
      line U87. For this purpose, SH-SY5Y and U87 co-cultures were treated with Sal,
      and this conditioned medium containing mediators, including the potential
      effector CCL2, was isolated and applied to THP-1 cells. This treatment resulted
      in approximately 19 % cell proliferation as well as activation of mTOR and
      induction of phosphorylated 4E-BP1, S6K1, PI3K, and AKT proteins. Treatment with
      rapamycin, an mTOR inhibitor, attenuated the proliferation of THP-1 cells. U87
      glial cells were essential for this as medium conditioned without them had no
      effect on THP-1 cells. These results suggest a positive effect of THP-1 cells on
      Sal-induced neurotoxicity in a cellular model of PD and this is likely mediated
      by the enhancement of cell proliferation through activation of the mTOR signaling
      pathway. Hence, PBMCs and their mTOR signaling pathway could be of therapeutic
      benefit in treating the endogenous neurotoxin-induced neuroinflammation in PD.

PMID- 25773263
TI  - One pot synthesis of highly luminescent polyethylene glycol anchored carbon dots
      functionalized with a nuclear localization signal peptide for cell nucleus
      imaging.
AB  - Strong blue fluorescent polyethylene glycol (PEG) anchored carbon nitride dots
      (CDs@PEG) with a high quantum yield (QY) of 75.8% have been synthesized by a one
      step hydrothermal treatment. CDs with a diameter of ca. 6 nm are well dispersed
      in water and present a graphite-like structure. Photoluminescence (PL) studies
      reveal that CDs display excitation-dependent behavior and are stable under
      various test conditions. Based on the as-prepared CDs, we designed novel cell
      nucleus targeting imaging carbon dots functionalized with a nuclear localization
      signal (NLS) peptide. The favourable biocompatibilities of CDs and NLS modified
      CDs (NLS-CDs) are confirmed by in vitro cytotoxicity assays. Importantly,
      intracellular localization experiments in MCF7 and A549 cells demonstrate that
      NLS-CDs could be internalized in the nucleus and show blue light, which indicates
      that CDs may serve as cell nucleus imaging probes. 

PMID- 25773264
TI  - The ASPHO 2015 Distinguished Career Award goes to Dr. Winfred C. Wang, MD.

PMID- 25773265
TI  - DNA damage foci: Meaning and significance.
AB  - The discovery of DNA damage response proteins such as gammaH2AX, ATM, 53BP1,
      RAD51, and the MRE11/RAD50/NBS1 complex, that accumulate and/or are modified in
      the vicinity of a chromosomal DNA double-strand break to form microscopically
      visible, subnuclear foci, has revolutionized the detection of these lesions and
      has enabled studies of the cellular machinery that contributes to their repair.
      Double-strand breaks are induced directly by a number of physical and chemical
      agents, including ionizing radiation and radiomimetic drugs, but can also arise
      as secondary lesions during replication and DNA repair following exposure to a
      wide range of genotoxins. Here we aim to review the biological meaning and
      significance of DNA damage foci, looking specifically at a range of different
      settings in which such markers of DNA damage and repair are being studied and
      interpreted.

PMID- 25773266
TI  - Molecular structure effects on the post irradiation diffusion in polymer gel
      dosimeters.
AB  - Polymer gel dosimeters have specific advantages for recording 3D radiation dose
      distribution in diagnostic and therapeutic medical applications. But, even in
      systems where the 3D structure is usually maintained for long periods of time
      after irradiation, it is still not possible to eliminate the diffusion of the
      different species in the regions of dose gradients within the gel. As a
      consequence, information of the dose loses quality over time. In the pursuit of a
      solution and to improve the understanding of this phenomenon a novel system based
      on itaconic acid and N-N'-methylene-bisacrylamide (BIS) is hereby proposed.
      Effects of changes in the chemical structure of the monomers over the dosimetric
      sensitivity and over the post-irradiation diffusion of species was studied. In
      this study, one of the carboxylic groups of the itaconic acid molecule was
      modified with aniline to obtain molecules with similar reactivity but different
      molecular sizes. Then, dosimeters based on these modified species and on the
      original ITA molecules were irradiated in an X-ray tomography apparatus at
      different doses up to 173Gy. Afterwards, the resulting dosimeters were
      characterized by Raman spectroscopy and optical absorbance in order to study
      their feasibility and capabilities as dosimetric systems, and by optical-CT to
      analyze the post irradiation diffusion. 

PMID- 25773267
TI  - Braces and orthoses for treating osteoarthritis of the knee.
AB  - BACKGROUND: Individuals with osteoarthritis (OA) of the knee can be treated with
      a knee brace or a foot/ankle orthosis. The main purpose of these aids is to
      reduce pain, improve physical function and, possibly, slow disease progression.
      This is the second update of the original review published in Issue 1, 2005, and
      first updated in 2007. OBJECTIVES: To assess the benefits and harms of braces and
      foot/ankle orthoses in the treatment of patients with OA of the knee. SEARCH
      METHODS: We searched the Cochrane Central Register of Controlled Trials
      (CENTRAL), MEDLINE and EMBASE (current contents, HealthSTAR) up to March 2014. We
      screened reference lists of identified trials and clinical trial registers for
      ongoing studies. SELECTION CRITERIA: Randomised and controlled clinical trials
      investigating all types of braces and foot/ankle orthoses for OA of the knee
      compared with an active control or no treatment. DATA COLLECTION AND ANALYSIS:
      Two review authors independently selected trials and extracted data. We assessed
      risk of bias using the 'Risk of bias' tool of The Cochrane Collaboration. We
      analysed the quality of the results by performing an overall grading of evidence
      by outcome using the GRADE (Grades of Recommendation, Assessment, Development and
      Evaluation) approach. As a result of heterogeneity of studies, pooling of outcome
      data was possible for only three insole studies. MAIN RESULTS: We included 13
      studies (n = 1356): four studies in the first version, three studies in the first
      update and six additional studies (n = 529 participants) in the second update. We
      included studies that reported results when study participants with early to
      severe knee OA (Kellgren & Lawrence grade I-IV) were treated with a knee brace
      (valgus knee brace, neutral brace or neoprene sleeve) or an orthosis (laterally
      or medially wedged insole, neutral insole, variable or constant stiffness shoe)
      or were given no treatment. The main comparisons included (1) brace versus no
      treatment; (2) foot/ankle orthosis versus no treatment or other treatment; and
      (3) brace versus foot/ankle orthosis. Seven studies had low risk, two studies had
      high risk and four studies had unclear risk of selection bias. Five studies had
      low risk, three studies had high risk and five studies had unclear risk of
      detection bias. Ten studies had high risk and three studies had low risk of
      performance bias. Nine studies had low risk and four studies had high risk of
      reporting bias.Four studies compared brace versus no treatment, but only one
      provided useful data for meta-analysis at 12-month follow-up. One study (n = 117,
      low-quality evidence) showed lack of evidence of an effect on visual analogue
      scale (VAS) pain scores (absolute percent change 0%, mean difference (MD) 0.0,
      95% confidence interval (CI) -0.84 to 0.84), function scores (absolute percent
      change 1%, MD 1.0, 95% CI -2.98 to 4.98) and health-related quality of life
      scores (absolute percent change 4%, MD -0.04, 95% CI -0.12 to 0.04) after 12
      months. Many participants stopped their initial treatment because of lack of
      effect (24 of 60 participants in the brace group and 14 of 57 participants in the
      no treatment group; absolute percent change 15%, risk ratio (RR) 1.63, 95% CI
      0.94 to 2.82). The other studies reported some improvement in pain, function and
      health-related quality of life (P value <= 0.001). Stiffness and treatment
      failure (need for surgery) were not reported in the included studies.For the
      comparison of laterally wedged insole versus no insole, one study (n = 40, low
      quality evidence) showed a lower VAS pain score in the laterally wedged insole
      group (absolute percent change 16%, MD -1.60, 95% CI -2.31 to -0.89) after nine
      months. Function, stiffness, health-related quality of life, treatment failure
      and adverse events were not reported in the included study.For the comparison of
      laterally wedged versus neutral insole after pooling of three studies (n = 358,
      moderate-quality evidence), little evidence was found of an effect on numerical
      rating scale (NRS) pain scores (absolute percent change 1.0%, MD 0.1, 95% CI 
      0.45 to 0.65), Western Ontario-McMaster Osteoarthritis Scale (WOMAC) stiffness
      scores (absolute percent change 0.1%, MD 0.07, 95% CI -4.96 to 5.1) and WOMAC
      function scores (absolute percent change 0.9%, MD 0.94, 95% CI - 2.98 to 4.87)
      after 12 months. Evidence of an effect on health-related quality of life scores
      (absolute percent change 1.0%, MD 0.01, 95% CI -0.05 to 0.03) was lacking in one
      study (n = 179, moderate-quality evidence). Treatment failure and adverse events
      were not studied for this comparison in the included studies.Data for the
      comparison of laterally wedged insole versus valgus knee brace could not be
      pooled. After six months' follow-up, no statistically significant difference was
      noted in VAS pain scores (absolute percent change -2.0%, MD -0.2, 95% CI -1.15 to
      0.75) and WOMAC function scores (absolute percent change 0.1%, MD 0.1, 95% CI 
      7.26 to 0.75) in one study (n = 91, low-quality evidence); however both groups
      showed improvement. Stiffness, health-related quality of life, treatment failure
      and adverse events were not reported in the included studies for this comparison.
      AUTHORS' CONCLUSIONS: Evidence was inconclusive for the benefits of bracing for
      pain, stiffness, function and quality of life in the treatment of patients with
      medial compartment knee OA. On the basis of one laterally wedged insole versus no
      treatment study, we conclude that evidence of an effect on pain in patients with
      varus knee OA is lacking. Moderate-quality evidence shows lack of an effect on
      improvement in pain, stiffness and function between patients treated with a
      laterally wedged insole and those treated with a neutral insole. Low-quality
      evidence shows lack of an effect on improvement in pain, stiffness and function
      between patients treated with a valgus knee brace and those treated with a
      laterally wedged insole. The optimal choice for an orthosis remains unclear, and
      long-term implications are lacking.

PMID- 25773270
TI  - Reductive photocatalysis and smart inks.
AB  - Semiconductor-sensitised photocatalysis is a well-established and growing area of
      research, innovation and commercialisation; the latter being mostly limited to
      the use of TiO2 as the semiconductor. Most of the work on semiconductor
      photocatalytic systems uses oxygen as the electron acceptor and explores a wide
      range of electron donors; such systems can be considered to be examples of
      oxidative photocatalysis, OP. OP underpins most current examples of commercial
      self-cleaning materials, such as: glass, tiles, concrete, paint and fabrics. OP,
      and its myriad of applications, have been reviewed extensively over the years
      both in this journal and elsewhere. However, the ability of TiO2, and other
      semiconductor sensitisers, to promote reductive photocatalysis, RP, especially of
      dyes, is significant and, although less well-known, is of growing importance. In
      such systems, the source of the electrons is some easily oxidised species, such
      as glycerol. One recent, significant example of a RP process is with respect to
      photocatalyst activity indicator inks. paiis, which provide a measure of the
      activity of a photocatalytic film under test via the rate of change of colour of
      the dye in the ink coating due to irreversible RP. In contrast, by incorporating
      the semiconductor sensitiser in the ink, rather than outside it, it is possible
      to create an effective UV dosimeter, based on RP, which can be used as a sun-burn
      warning indicator. In the above examples the dye is reduced irreversibly, but
      when the photocatalyst in an ink is used to reversibly photoreduce a dye, a
      novel, colourimetric oxygen-sensitive indicator ink can be created, which has
      commercial potential in the food packaging industry. Finally, if no dye is
      present in the ink, and the semiconductor photocatalyst-loaded ink film coats an
      easily reduced substrate, such as a metal oxide film, then it can be used to
      reduce the latter and so, for example, clean up tarnished steel. The above are
      examples of smart inks, i.e. inks that are active and provide either dynamic
      information (such as UV dose or O2 level) or a useful function (such as tarnish
      removal), and all work via a RP process and are reviewed here. 

PMID- 25773269
TI  - Difference between patients' and clinicians' perception of pouch dysfunction and
      its impact on quality of life following restorative proctocolectomy.
AB  - AIM: The Pouch Dysfunction Score (PDS) is a five-item instrument that evaluates
      bowel function and quality of life following restorative proctocolectomy for
      ulcerative colitis. The PDS includes items that have a significantly negative
      impact on quality of life from the patient's point of view. The study aimed to
      establish how pouch dysfunction is perceived by clinicians in relation to
      patients experience. METHOD: Fifty-eight leading clinicians in the field of
      inflammatory bowel disease were invited to complete two PDS-based exercises. In
      part 1, they received a list of the 12 bowel symptoms from which the PDS had been
      developed and were asked to identify and rank (in order of severity) the five
      they thought had the most significantly negative impact on quality of life. In
      part 2, they were given the list of symptoms perceived by patients to be most
      troublesome and were then required to enter a score that they thought was
      appropriate for each item according to the impact on quality of life. RESULTS:
      Forty-three clinicians responded, and each correctly identified one to three
      items selected by patients and included in the PDS. Severity of urgency was
      selected by 29 (67%) clinicians, and four (9%) rated it to be the most important.
      Incomplete emptying after defaecation was selected by 10 (23%). Frequency of
      defaecation and the use of anti-diarrhoeal medication were selected by 14 (33%)
      and three (7%) clinicians, respectively. Twenty-six (60%) did not include
      incomplete emptying and 25 (58%) did not include uncontrolled loss of stool in
      their selection. CONCLUSION: This study demonstrates that clinicians do not have
      a great understanding of the symptoms of pouch dysfunction that really matter to
      the patient.

PMID- 25773271
TI  - Closed-loop control of inspired oxygen in premature infants.
AB  - Systems for closed-loop control of inspired oxygen have been developed to improve
      the maintenance of oxygenation targets in premature infants and reduce
      hyperoxemia, hypoxemia, and exposure to high inspired oxygen levels. This review
      describes some of the clinical studies that have evaluated the efficacy of these
      systems in oxygen targeting.

PMID- 25773272
TI  - Formation and optical properties of fluorescent gold nanoparticles obtained by
      matrix sputtering method with volatile mercaptan molecules in the vacuum chamber
      and consideration of their structures.
AB  - This paper proposes a novel methodology to synthesize highly fluorescent gold
      nanoparticles (NPs) with a maximum quantum yield of 16%, in the near-infrared
      (IR) region. This work discusses the results of using our (previously developed)
      matrix sputtering method to introduce mercaptan molecules, alpha-thioglycerol,
      inside the vacuum sputtering chamber, during the synthesis of metal NPs. The
      evaporation of alpha-thioglycerol inside the chamber enables to coordinate to the
      "nucleation stage" very small gold nanoclusters in the gas phase, thus retaining
      their photophysical characteristics. As observed through transmission electron
      microscopy, the size of the Au NPs obtained with the addition of alpha
      thioglycerol varied from approximately 2-3 nm to approximately 5 nm. Plasmon
      absorption varied with the size of the resultant nanoparticles. Thus, plasmon
      absorption was observed at 2.4 eV in the larger NPs. However, it was not
      observed, and instead a new peak was found at approximately 3.4 eV, in the
      smaller NPs that resulted from the introduction of alpha-thioglycerol. The Au NPs
      stabilized by the alpha-thioglycerol fluoresced at approximately 1.8 eV, and the
      maximum wavelength shifted toward the red, in accordance with the size of the
      NPs. A maximum fluorescent quantum yield of 16% was realized under the optimum
      conditions, and this value is extremely high compared to values previously
      reported on gold NPs and clusters (generally ~1%). To our knowledge, however, Au
      NPs of size >2 nm usually do not show strong fluorescence. By comparison with
      results reported in previous literature, it was concluded that these highly
      fluorescent Au NPs consist of gold-mercaptan complexes. The novel method
      presented in this paper therefore opens a new door for the effective control of
      size, photophysical characteristics, and structure of metal NPs. It is hoped that
      this research contributes significantly to the science in this field. 

PMID- 25773273
TI  - Albuminuria and reduced glomerular filtration rate for predicting the renal
      outcomes in type 2 diabetic patients.
AB  - AIM: The first clinical manifestation of diabetic kidney disease is usually the
      development of microalbuminuria. However, recent studies have focused on diabetic
      patients with reduced glomerular filtration rate (GFR) without albuminuria. To
      evaluate the association of albuminuria and GFR with renal outcomes, we performed
      an observational study. METHODS: A total of 3231 type 2 diabetic patients were
      included in this study between 2003 and 2005. There were 1249 women and the mean
      age was 59 +/- 12 years. The renal endpoints were defined as the initiation of
      renal replacement therapy (RRT) or 50% reduction from the baseline of estimated
      GFR (eGFR). RESULTS: At baseline, 669 (20.7%) patients had eGFR <60 mL/min per
      1.73 m(2) and 1134 (35.1%) had albuminuria. During the mean follow-up period of
      5.9 +/- 1.6 years, 107 patients initiated RRT. A 50% reduction of eGFR from the
      baseline value was found in 279 patients. None of the normoalbuminuric subjects
      with or without reduced eGFR required RRT during the observational period (P <
      0.01). Compared to normoalbuminuria patients with eGFR >=60 mL/min per 1.73 m(2)
      at baseline, the group of normoalbuminuria patients with reduced eGFR had a 2.5
      fold risk of developing the renal endpoints, (95% confidence interval (CI): 1.0
      6.3, P = 0.053). Patients with microalbuminuria with eGFR >=60 mL/min per 1.73
      m(2) at baseline had a 5.0-fold risk of developing the evaluated renal endpoints
      (95% CI: 2.8-8.8, P < 0.001). CONCLUSION: Albuminuria was a significant predictor
      for the evaluated renal endpoints, but the impact of eGFR is likely to be less
      than that of albuminuria.

PMID- 25773274
TI  - Children's prosocial behavioural intentions towards outgroup members.
AB  - When will children decide to help outgroup peers? We examined how intergroup
      competition, social perspective taking (SPT), and empathy influence children's (5
      10 years, N = 287) prosocial intentions towards outgroup members. Study 1 showed
      that, in a minimal group situation, prosociality was lower in an intergroup
      competitive than in a non-competitive or interpersonal context. Study 2 revealed
      that, in a real groups situation involving intergroup competition, prosociality
      was associated with higher empathy and lower competitive motivation. In a
      subsequent non-competitive context, there were age differences in the impact of
      SPT and competitive motivation. With age, relationships strengthened between SPT
      and prosociality (positively) and between competitiveness and prosociality
      (negatively). Among older children, there was a carry-over effect whereby
      feelings of intergroup competitiveness aroused by the intergroup competitive
      context suppressed outgroup prosociality in the following non-competitive
      context. Theoretical and practical implications for improving children's
      intergroup relationships are discussed. 

PMID- 25773275
TI  - Metal-organic framework based upon the synergy of a Bronsted acid framework and
      Lewis acid centers as a highly efficient heterogeneous catalyst for fixed-bed
      reactions.
AB  - We report a strategy of combining a Bronsted acid metal-organic framework (MOF)
      with Lewis acid centers to afford a Lewis acid@Bronsted acid MOF with high
      catalytic activity, as exemplified in the context of MIL-101-Cr-SO3H.Al(III).
      Because of the synergy between the Bronsted acid framework and the Al(III) Lewis
      acid centers, MIL-101-Cr-SO3H.Al(III) demonstrates excellent catalytic
      performance in a series of fixed-bed reactions, outperforming two benchmark
      zeolite catalysts (H-Beta and HMOR). Our work therefore not only provides a new
      approach to achieve high catalytic activity in MOFs but also paves a way to
      develop MOFs as a new type of highly efficient heterogeneous catalysts for fixed
      bed reactions. 

PMID- 25773277
TI  - Human atlastin GTPases mediate differentiated fusion of endoplasmic reticulum
      membranes.

PMID- 25773276
TI  - Phosphorylation of Atg31 is required for autophagy.
AB  - Autophagy is an evolutionarily conserved cellular process which degrades
      intracellular contents. The Atg17-Atg31-Atg29 complex plays a key role in
      autophagy induction by various stimuli. In yeast, autophagy occurs with
      autophagosome formation at a special site near the vacuole named the pre
      autophagosomal structure (PAS). The Atg17-Atg31-Atg29 complex forms a scaffold
      for PAS organization, and recruits other autophagy-related (Atg) proteins to the
      PAS. Here, we show that Atg31 is a phosphorylated protein. The phosphorylation
      sites on Atg31 were identified by mass spectrometry. Analysis of mutants in which
      the phosphorylated amino acids were replaced by alanine, either individually or
      in various combinations, identified S174 as the functional phosphorylation site.
      An S174A mutant showed a similar degree of autophagy impairment as an Atg31
      deletion mutant. S174 phosphorylation is required for autophagy induced by
      various autophagy stimuli such as nitrogen starvation and rapamycin treatment.
      Mass spectrometry analysis showed that S174 is phosphorylated constitutively, and
      expression of a phosphorylation-mimic mutant (S174D) in the Atg31 deletion strain
      restores autophagy. In the S174A mutant, Atg9-positive vesicles accumulate at the
      PAS. Thus, S174 phosphorylation is required for formation of autophagosomes,
      possibly by facilitating the recycling of Atg9 from the PAS. Our data demonstrate
      the role of phosphorylation of Atg31 in autophagy. 

PMID- 25773278
TI  - Structural basis of PKM2 regulation.

PMID- 25773279
TI  - Monogenic diabetes: the treatment options.

PMID- 25773280
TI  - Pioglitazone: are rumours of its death exaggerated?

PMID- 25773281
TI  - Neither evidence from the PROactive study nor the KPNC supports pioglitazone as a
      tumour promoter.

PMID- 25773282
TI  - Pioglitazone: reports of its death are greatly exaggerated - it is alive and
      ready to resume saving lives.

PMID- 25773283
TI  - Ant-mediated ecosystem functions on a warmer planet: effects on soil movement,
      decomposition and nutrient cycling.
AB  - 1. Direct and indirect consequences of global warming on ecosystem functions and
      processes mediated by invertebrates remain understudied but are likely to have
      major impacts on ecosystems in the future. Among animals, invertebrates are
      taxonomically diverse, responsive to temperature changes, and play major
      ecological roles which also respond to temperature changes. 2. We used a mesocosm
      experiment to evaluate impacts of two warming treatments (+3.5 and +5  degrees C,
      set-points) and the presence and absence of the ant Formica subsericea (a major
      mediator of processes in north temperate ecosystems) on decomposition rate, soil
      movement, soil respiration and nitrogen availability. 3, Replicate 19-L mesocosms
      were placed outdoors in lathe houses and continuously warmed for 30 days in 2011
      and 85 days in 2012. Warming treatments mimicked expected temperature increases
      for future climates in eastern North America. 4. In both years, the amount of
      soil displaced and soil respiration increased in the warming and ant presence
      treatments (soil movement: 73-119%; soil respiration: 37-48% relative to the
      control treatments without ants). 5. Decomposition rate and nitrogen availability
      tended to decrease in the warmest treatments (decomposition rate: -26 to -30%;
      nitrate availability: -11 to -42%). 6. Path analyses indicated that ants had
      significant short-term direct and indirect effects on the studied ecosystem
      processes. These results suggest that ants may be moving more soil and building
      deeper nests to escape increasing temperatures, but warming may also influence
      their direct and indirect effects on soil ecosystem processes.

PMID- 25773284
TI  - Assessing the TP53 marker type in patients treated with or without neoadjuvant
      chemotherapy for resectable colorectal liver metastases: a p53 Research Group
      study.
AB  - The type of a biomarker - whether it is prognostic or predictive - is frequently
      not known, although such information is crucial for assessing the clinical value
      of a marker. In order to evaluate the type of marker TP53 is, we identified a
      cohort of 76 patients with colorectal liver metastases (CLM), homogeneously
      staged as resectable, who had been treated either with or without fluorouracil
      based neoadjuvant chemotherapy. The TP53 genotype was assessed retrospectively
      from paraffin-embedded, diagnostic tumour biopsies using a standardised, p53 gene
      specific sequencing protocol (mark53((r)) kit). The overall median survival was
      44.2 months, and the overall TP53 mutation frequency was 55%. A significant
      interaction was observed between chemotherapy and TP53 status (P = 0.045). To
      illustrate this effect, the 51 patients with and the 25 patients without
      neoadjuvant chemotherapy were described separately. In patients with neoadjuvant
      chemotherapy, mutated TP53 was significantly associated with poor survival (P =
      0.0025), resulting in five-year survival rates of 22%, compared to 60% in
      patients with normal TP53. The hazard ratio was 3.12 (95% confidence intervals
      (CI): 1.46-6.95) to the disadvantage of TP53-mutated patients and 5.49 (P =
      0.0001; 95% CI: 2.28-13.24) after adjustment for known prognostic factors. In
      patients treated with surgery alone, a mutated TP53 did not have a negative
      effect on survival (P = 0.54). A mutated TP53 status independently predicted
      survival disadvantage in CLM patients in the presence, but not in the absence, of
      neoadjuvant chemotherapy. Our data suggest that TP53 might be a pure predictive
      marker. 

PMID- 25773285
TI  - Long-term follow-up in preperimetric open-angle glaucoma: progression rates and
      associated factors.

PMID- 25773286
TI  - Reply: To PMID 25448320.

PMID- 25773287
TI  - Choroidal thickness and volume in healthy young white adults and the
      relationships between them and axial length, ammetropy and sex.

PMID- 25773288
TI  - Reply: To PMID 24907431.

PMID- 25773289
TI  - Voxel-based analysis of the immediate early gene, c-jun, in the honey bee brain
      after a sucrose stimulus.
AB  - Immediate early genes (IEGs) have served as useful markers of brain neuronal
      activity in mammals, and more recently in insects. The mammalian canonical IEG, c
      jun, is part of regulatory pathways conserved in insects and has been shown to be
      responsive to alarm pheromone in honey bees. We tested whether c-jun was
      responsive in honey bees to another behaviourally relevant stimulus, sucrose, in
      order to further identify the brain regions involved in sucrose processing. To
      identify responsive regions, we developed a new method of voxel-based analysis of
      c-jun mRNA expression. We found that c-jun is expressed in somata throughout the
      brain. It was rapidly induced in response to sucrose stimuli, and it responded in
      somata near the antennal and mechanosensory motor centre, mushroom body calices
      and lateral protocerebrum, which are known to be involved in sucrose processing.
      c-jun also responded to sucrose in somata near the lateral suboesophageal
      ganglion, dorsal optic lobe, ventral optic lobe and dorsal posterior
      protocerebrum, which had not been previously identified by other methods. These
      results demonstrate the utility of voxel-based analysis of mRNA expression in the
      insect brain. 

PMID- 25773290
TI  - Glut-1, Best Immunohistochemical Marker for Perineurial Cells: A Note of Caution.

PMID- 25773291
TI  - Site-specific immobilization of protein layers on gold surfaces via orthogonal
      sortases.
AB  - We report a site-specific, sortase-mediated ligation to immobilize proteins layer
      by-layer on a gold surface. Recombinant fluorescent proteins with a Sortase A
      recognition tag at the C-terminus were immobilized on peptide-modified gold
      surfaces. We used two sortases with different substrate specificities
      (Streptococcus pyogenes Sortase A and Staphylococcus aureus Sortase A) to
      immobilize layers of GFP and mCherry site-specifically on the gold surface.
      Surfaces were characterized using fluorescence and atomic force microscopy after
      immobilizing each layer of protein. Fluorescent micrographs showed that both
      protein immobilization on the modified gold surface and protein oligomerization
      are sortase-dependent. AFM images showed that either homogenous protein
      monolayers or layers of protein oligomers can be generated using appropriately
      tagged substrate proteins. Using Sortase A variants with orthogonal peptide
      substrate specificities, site-specific immobilization of appropriately tagged GFP
      onto a layer of immobilized mCherry was achieved without disruption of the
      underlying protein layer. 

PMID- 25773292
TI  - Cutaneous granulomas in the setting of primary immunodeficiency: a report of four
      cases and review of the literature.
AB  - IMPORTANCE: Cutaneous granulomas without an identifiable infectious etiology are
      a rare manifestation of primary immunodeficiency (ID). These cutaneous lesions
      can be misdiagnosed, often as sarcoidosis, when the skin findings precede the
      diagnosis of immunodeficiency. OBJECTIVE: We present four cases from our
      institution and review the literature in order to emphasize the clinical
      relevance of this association, discuss the histologic and immunohistochemical
      features, and explore possible pathogenic mechanisms of granuloma formation.
      EVIDENCE REVIEW: We retrospectively reviewed case reports of all patients
      presenting with cutaneous granulomas in the setting of primary immunodeficiency.
      Cases with insufficient information to confirm an immunodeficiency state were
      excluded. Four patients from our clinic were included, for 54 total cases.
      FINDINGS: The majority of cutaneous granulomas are seen in three types of
      immunodeficiencies: ataxia-telangiectasia, severe combined immunodeficiency, and
      combined variable immunodeficiency. Twenty-six percent of patients developed
      cutaneous granulomas prior to their immunodeficiency diagnosis. Histologically,
      various granulomatous patterns have been described. Immunohistochemistry revealed
      a CD4+/CD8+ lymphocyte ratio of less than or equal to 1 in our four patients,
      which may help differentiate cutaneous granulomas in primary ID from sarcoidal
      granulomas that typically show a CD4+ predominance. CONCLUSIONS AND RELEVANCE:
      Cutaneous granulomas are a rare manifestation of primary ID and occur
      predominantly in immunodeficiencies that affect T and B cell compartments.

PMID- 25773294
TI  - Mapping a major QTL for malt extract of barley from a cross between TX9425 * Naso
      Nijo.
AB  - KEY MESSAGE: One major QTL-controlling malt extract was identified on 2H, based
      on the data from four different environments and a large number of DH lines,
      determining 48% of phenotypic variation. This QTL is of a high value for marker
      assisted selection. Improving malting quality traits is one of the major breeding
      objectives for barley breeding programmes. Among different quality traits, malt
      extract is one of the most important, determining the yield of beer production.
      The use of molecular markers linked to loci affecting the quality traits can
      greatly improve selection efficiency. However, the discovery of closely linked
      markers relies on not only the availability of the loci, but the accuracy of
      phenotyping. In this experiment, 188 doubled-haploid lines derived from the cross
      between a Japanese malting barley and a Chinese feed barley were grown in four
      different environments (two sites * 2 years). Different quality traits were
      determined and used to map QTL for these traits. Several QTLs were identified for
      different quality traits. One major QTL-controlling malt extract was identified
      on 2H and determined 48% of phenotypic variation with the closest marker of
      GBM1121. This QTL was consistently expressed in all four environments and is of a
      high value for marker-assisted selection in malting barley breeding.

PMID- 25773296
TI  - The dark side of a fitful night: new studies linking sleep apnea and other
      disruptions to cancer add to evidence that poor sleep can be deadly.

PMID- 25773295
TI  - Exome sequencing of case-unaffected-parents trios reveals recessive and de novo
      genetic variants in sporadic ALS.
AB  - The contribution of genetic variants to sporadic amyotrophic lateral sclerosis
      (ALS) remains largely unknown. Either recessive or de novo variants could result
      in an apparently sporadic occurrence of ALS. In an attempt to find such variants
      we sequenced the exomes of 44 ALS-unaffected-parents trios. Rare and potentially
      damaging compound heterozygous variants were found in 27% of ALS patients,
      homozygous recessive variants in 14% and coding de novo variants in 27%. In 20%
      of patients more than one of the above variants was present. Genes with recessive
      variants were enriched in nucleotide binding capacity, ATPase activity, and the
      dynein heavy chain. Genes with de novo variants were enriched in transcription
      regulation and cell cycle processes. This trio study indicates that rare private
      recessive variants could be a mechanism underlying some case of sporadic ALS, and
      that de novo mutations are also likely to play a part in the disease. 

PMID- 25773298
TI  - Outcomes after acute ischemic stroke in the United States: does residential ZIP
      code matter?
AB  - BACKGROUND: We sought to analyze the impact of socioeconomic status (SES) on in
      hospital outcomes, cost of hospitalization, and resource use after acute ischemic
      stroke. METHODS AND RESULTS: We used the 2003-2011 Nationwide Inpatient Sample
      database for this analysis. All admissions with a principal diagnosis of acute
      ischemic stroke were identified by using International Classification of
      Diseases, Ninth Revision codes. SES was assessed by using median household income
      of the residential ZIP code for each patient. Quartile 1 and quartile 4 reflect
      the lowest-income and highest-income SES quartile, respectively. During a 9-year
      period, 775,905 discharges with acute ischemic stroke were analyzed. There was a
      progressive increase in the incidence of reperfusion on the first admission day
      across the SES quartiles (P-trend<0.001). In addition, we observed a significant
      reduction in discharge to nursing facility, across the SES quartiles (P
      trend<0.001). Although we did not observe a significant difference in in-hospital
      mortality across the SES quartiles in the overall cohort (P-trend=0.22), there
      was a significant trend toward reduced in-hospital mortality across the SES
      quartiles in younger patients (<75 years) (P-trend<0.001). The mean length of
      stay in the lowest-income quartile was 5.75 days, which was significantly higher
      compared with other SES quartiles. Furthermore, the mean adjusted cost of
      hospitalization among quartiles 2, 3, and 4, compared with quartile 1, was
      significantly higher by $621, $1238, and $2577, respectively. Compared with the
      lowest-income quartile, there was a significantly higher use of echocardiography,
      invasive angiography, and operative procedures, including carotid endarterectomy,
      in the highest-income quartile. CONCLUSIONS: Patients from lower-income quartiles
      had decreased reperfusion on the first admission day, compared with patients from
      higher-income quartiles. The cost of hospitalization of patients from higher
      income quartiles was significantly higher than that of patients from lowest
      income quartiles, despite longer hospital stays in the latter group. This might
      be partially attributable to a lower use of key procedures among patients from
      lowest-income quartile.

PMID- 25773300
TI  - Altered atrial metabolism: an underappreciated contributor to the initiation and
      progression of atrial fibrillation.

PMID- 25773299
TI  - LKB1 knockout mouse develops spontaneous atrial fibrillation and provides
      mechanistic insights into human disease process.
AB  - BACKGROUND: Atrial fibrillation (AF) is a complex disease process, and the
      molecular mechanisms underlying initiation and progression of the disease are
      unclear. Consequently, AF has been difficult to model. In this study, we have
      presented a novel transgenic mouse model of AF that mimics human disease and
      characterized the mechanisms of atrial electroanatomical remodeling in the
      genesis of AF. METHODS AND RESULTS: Cardiac-specific liver kinase B1 (LKB1)
      knockout (KO) mice were generated, and 47% aged 4 weeks and 95% aged 12 weeks
      developed spontaneous AF from sinus rhythm by demonstrating paroxysmal and
      persistent stages of the disease. Electrocardiographic characteristics of sinus
      rhythm were similar in KO and wild-type mice. Atrioventricular block and atrial
      flutter were common in KO mice. Heart rate was slower with persistent AF. In
      parallel with AF, KO mice developed progressive biatrial enlargement with
      inflammation, heterogeneous fibrosis, and loss of cardiomyocyte population with
      apoptosis and necrosis. Atrial tissue was infiltrated with inflammatory cells. C
      reactive protein, interleukin 6, and tumor necrosis factor alpha were
      significantly elevated in serum. KO atria demonstrated elevated reactive oxygen
      species and decreased AMP-activated protein kinase activity. Cardiomyocyte and
      myofibrillar ultrastructure were disrupted. Intercellular matrix and gap junction
      were interrupted. Connexins 40 and 43 were reduced. Persistent AF caused left
      ventricular dysfunction and heart failure. Survival and exercise capacity were
      worse in KO mice. CONCLUSIONS: LKB1 KO mice develop spontaneous AF from sinus
      rhythm and progress into persistent AF by replicating the human AF disease
      process. Progressive inflammatory atrial cardiomyopathy is the genesis of AF,
      through mechanistic electrical and structural remodeling.

PMID- 25773301
TI  - Ocean acidification research in the 'post-genomic' era: Roadmaps from the purple
      sea urchin Strongylocentrotus purpuratus.
AB  - Advances in nucleic acid sequencing technology are removing obstacles that
      historically prevented use of genomics within ocean change biology. As one of the
      first marine calcifiers to have its genome sequenced, purple sea urchins
      (Strongylocentrotus purpuratus) have been the subject of early research exploring
      genomic responses to ocean acidification, work that points to future experiments
      and illustrates the value of expanding genomic resources to other marine
      organisms in this new 'post-genomic' era. This review presents case studies of S.
      purpuratus demonstrating the ability of genomic experiments to address major
      knowledge gaps within ocean acidification. Ocean acidification research has
      focused largely on species vulnerability, and studies exploring mechanistic bases
      of tolerance toward low pH seawater are comparatively few. Transcriptomic
      responses to high pCO2 seawater in a population of urchins already encountering
      low pH conditions have cast light on traits required for success in future
      oceans. Secondly, there is relatively little information on whether marine
      organisms possess the capacity to adapt to oceans progressively decreasing in pH.
      Genomics offers powerful methods to investigate evolutionary responses to ocean
      acidification and recent work in S. purpuratus has identified genes under
      selection in acidified seawater. Finally, relatively few ocean acidification
      experiments investigate how shifts in seawater pH combine with other
      environmental factors to influence organism performance. In S. purpuratus,
      transcriptomics has provided insight into physiological responses of urchins
      exposed simultaneously to warmer and more acidic seawater. Collectively, these
      data support that similar breakthroughs will occur as genomic resources are
      developed for other marine species.

PMID- 25773302
TI  - Use of sibling relationship reconstruction to complement traditional monitoring
      in fisheries management and conservation of brown trout.
AB  - Declining trends in the abundance of many fish urgently call for more efficient
      and informative monitoring methods that would provide necessary demographic data
      for the evaluation of existing conservation, restoration, and management actions.
      We investigated how genetic sibship reconstruction from young-of-the-year brown
      trout (Salmo trutta L.) juveniles provides valuable, complementary demographic
      information that allowed us to disentangle the effects of habitat quality and
      number of breeders on juvenile density. We studied restored (n = 15) and control
      (n = 15) spawning and nursery habitats in 16 brown trout rivers and streams over
      2 consecutive years to evaluate the effectiveness of habitat restoration
      activities. Similar juvenile densities both in restored and control spawning and
      nursery grounds were observed. Similarly, no differences in the effective number
      of breeders, Nb(SA) , were detected between habitats, indicating that brown trout
      readily used recently restored spawning grounds. Only a weak relationship between
      the Nb(SA) and juvenile density was observed, suggesting that multiple factors
      affect juvenile abundance. In some areas, very low estimates of Nb(SA) were found
      at sites with high juvenile density, indicating that a small number of breeders
      can produce a high number of progeny in favorable conditions. In other sites,
      high Nb(SA) estimates were associated with low juvenile density, suggesting low
      habitat quality or lack of suitable spawning substrate in relation to available
      breeders. Based on these results, we recommend the incorporation of genetic
      sibship reconstruction to ongoing and future fish evaluation and monitoring
      programs to gain novel insights into local demographic and evolutionary processes
      relevant for fisheries management, habitat restoration, and conservation. 

PMID- 25773303
TI  - Adherence to the healthy Nordic food index, dietary composition, and lifestyle
      among Swedish women.
AB  - Background : Studies examining diet scores in relation to health outcomes are
      gaining ground. Thus, control for dietary factors not part of the score, and
      lifestyle associated with adherence, is required to allow for a causal
      interpretation of studies on diet scores and health outcomes. Objective : The
      study objective is to describe and investigate dietary composition, micronutrient
      density, lifestyle, socioeconomic factors, and adherence to the Nordic Nutrition
      Recommendations across groups defined by their level of adherence to a healthy
      Nordic food index (HNFI). The paper examines both dietary components included in
      the HNFI as well as dietary components, which are not part of the HNFI, to get a
      broad picture of the diet. Design : The study is cross-sectional and conducted in
      the Swedish Women's Lifestyle and Health cohort. We included 45,277 women, aged
      29-49 years at baseline (1991-1992). The HNFI was defined by six items:
      wholegrain bread, oatmeal, apples/pears, cabbages, root vegetables and
      fish/shellfish, using data from a food frequency questionnaire. Proportions,
      means and standard deviations were calculated in the entire cohort and by
      adherence groups. Results : Women scoring high on the HNFI had a higher energy
      intake, compared to low adherers. They had a higher intake of fiber and a higher
      micronutrient density (components of the HNFI), but also a higher intake of items
      not included in the HNFI: red/processed meats, sweets, and potatoes. They were on
      average more physically active and less likely to smoke. Conclusions : Adherence
      to the HNFI was associated with a generally healthier lifestyle and a high intake
      of health-beneficial components. However, it was also associated with a higher
      energy intake and a higher intake of foods without proven health benefits.
      Therefore, future studies on the HNFI and health outcomes should take into
      account potential confounding of dietary and lifestyle factors associated with
      the HNFI. 

PMID- 25773304
TI  - Scrimer: designing primers from transcriptome data.
AB  - With the rise of next-generation sequencing methods, it has become increasingly
      possible to obtain genomewide sequence data even for nonmodel species. Such data
      are often used for the development of single nucleotide polymorphism (SNP)
      markers, which can subsequently be screened in a larger population sample using a
      variety of genotyping techniques. Many of these techniques require appropriate
      locus-specific PCR and genotyping primers. Currently, there is no publicly
      available software for the automated design of suitable PCR and genotyping
      primers from next-generation sequence data. Here we present a pipeline called
      Scrimer that automates multiple steps, including adaptor removal, read mapping,
      selection of SNPs and multiple primer design from transcriptome data. The
      designed primers can be used in conjunction with several widely used genotyping
      methods such as SNaPshot or MALDI-TOF genotyping. Scrimer is composed of several
      reusable modules and an interactive bash workflow that connects these modules.
      Even the basic steps are presented, so the workflow can be executed in a step-by
      step manner. The use of standard formats throughout the pipeline allows data from
      various sources to be plugged in, as well as easy inspection of intermediate
      results with visualization tools of the user's choice.

PMID- 25773305
TI  - Fertile structures with in situ spores of a dipterid fern from the Triassic in
      southern China.
AB  - Clathropteris was a typical dipterid fern with well documented fossil record and
      was widely dispersed during the Mesozoic; however, our knowledge of fertile
      structures including in situ spores for this genus is still very limited. Here we
      report well-preserved compression specimens of Clathropteris obovata Oishi from
      the Late Triassic of Guangyuan, Sichuan Province, China. The specimens show round
      to oval and exindusiate sori, vertical to oblique annuli in sporangia, and in
      situ trilete spores with verrucate and baculate sculptures, which are comparable
      to dispersed spore genera of Converrucosisporites and Conbaculatisporites.
      Comparisons of relevant fossil taxa suggest that specimens of C. obovata from
      Triassic of China provide for the first time in Asia the detailed fertile
      structures with in situ spore characters of dipterid fossil Clathropteris. Unlike
      living Dipteris, Mesozoic fossils of Dipteridaceae show a high diversity and a
      range of complex morphology of in situ spores, thus are significant for the
      evolutionary links between Dipteridaceae and other related fern clade, including
      Gleicheniaceae and Matoniaceae of the Gleicheniales. 

PMID- 25773307
TI  - Malignancy associated with ovarian teratomas: frequency, histotypes, and
      diagnostic accuracy of intraoperative consultation.
AB  - Mature cystic teratomas are common ovarian germ cell tumors that rarely undergo
      malignant transformation, and intraoperative consultation is generally not
      warranted. The aims of this study were to review a large number of ovarian
      teratomas (OTs), to document the rate and histotypes of associated malignancy,
      and to identify parameters that may be associated with malignancy. In this study,
      a retrospective medical record review of patients diagnosed as having OTs from
      2002 to 2011 was performed. Patient age, tumor size, type, and laterality were
      obtained from pathology reports and operative notes. A total of 956 OTs that
      ranged in size from 0.3 to 45 cm were identified. Intraoperative consultation was
      requested in a total of 316 (33.1%) of 956. Intraoperative gross evaluation only
      was performed on 211 (66.8%) of 316, of which 4 cases were malignant on final
      diagnosis. Frozen section was performed on 105 (33.2%) of 316, of which 12 were
      malignant on final diagnosis. The final diagnoses of all OT cases were as
      follows: 26 (2.7%) of 956 were associated with malignant tumors. The latter were
      larger than benign cases (average sizes, 11.2 cm vs 6.5 cm; P < .001), and
      patients with malignant tumors were significantly older than those with benign
      mature cystic teratoma (48.7 years vs 38.8 years, P < .001). The sensitivity and
      positive predictive value of frozen section examination during the intraoperative
      consultation for the detection of malignancy in OTs are 80% and 100%,
      respectively. In conclusion, patient age and large tumor size were associated
      with malignancy in this data set. Mucinous and serous borderline tumors were more
      common than squamous cell carcinoma in our cohort. 

PMID- 25773306
TI  - Persistent history of the bird-dispersed arctic-alpine plant Vaccinium vitis
      idaea L. (Ericaceae) in Japan.
AB  - Arctic-alpine plants have expanded and contracted their ranges in response to the
      Pleistocene climate oscillations. Today, many arctic-alpine plants have vast
      distributions in the circumarctic region as well as marginal, isolated
      occurrences in high mountains at lower latitudes. These marginal populations may
      represent relict, long-standing populations that have persisted for several
      cycles of cold and warm climate during the Pleistocene, or recent occurrences
      that either result from southward step-wise migration during the last glacial
      period or from recent long-distance dispersal. In light of these hypotheses, we
      investigated the biogeographic history of the marginal Japanese populations of
      the widespread arctic-alpine plant Vaccinium vitis-idaea (Ericaceae), which is
      bird-dispersed, potentially over long distances. We sequenced three nuclear loci
      and one plastid DNA region in 130 individuals from 65 localities covering its
      entire geographic range, with a focus on its marginal populations in Japan. We
      found a homogenous genetic pattern across its enormous range based on the loci
      analysed, in contrast to the geographically structured variation found in a
      previous study of amplified fragment length polymorphisms in this species.
      However, we found several unique haplotypes in the Japanese populations,
      excluding the possibility that these marginal populations result from recent
      southward migration. Thus, even though V. vitis-idaea is efficiently dispersed
      via berries, our study suggests that its isolated populations in Japan have
      persisted during several cycles of cold and warm climate during the Pleistocene. 

PMID- 25773308
TI  - The impact of delaying elective resection of diverticulitis on laparoscopic
      conversion rate.
AB  - BACKGROUND: Guideline-concordant delay in elective laparoscopic colectomy for
      diverticulitis may result in repeated bouts of inflammation. We aimed to
      determine whether conversion rates from elective laparoscopic colectomy are
      higher after multiple episodes of diverticulitis. METHODS: Prospective cohort
      study evaluating laparoscopic colectomy conversion rates for diverticulitis from
      42 hospitals was conducted. RESULTS: Between 2010 and 2013, 1,790 laparoscopic
      colectomies for diverticulitis (mean age 57.8 +/- 13; 47% male) resulted in 295
      (16.5%) conversions. Conversion occurred more frequently in nonelective
      operations (P < .001) and with fistula indications (P = .012). Conversion rates
      decreased with surgeon case volume (P = .028). Elective colectomy exclusively for
      episode-based indications (n = 784) had a conversion rate of 12.9%. Increasing
      episodes of diverticulitis were not associated with higher conversion rates, even
      among surgeons with similar experience levels. CONCLUSIONS: Conversion from
      laparoscopic colectomy for diverticulitis did not increase after multiple
      episodes of diverticulitis. Delaying elective resection appears to not prevent
      patients from the benefits of laparoscopy.

PMID- 25773309
TI  - Weight bearing the same day versus non-weight bearing for 4 weeks in Achilles
      tendon rupture.
AB  - INTRODUCTION: Achilles tendon rupture (ATR) often occurs in 40- to 50-year-old
      men. Multiple studies discuss the correct treatment strategy based on surgical or
      nonsurgical intervention, including early mobilization. We aimed to compare the
      outcomes of bearing weight on the same day with non-weight bearing over a 4-week
      period of ATR patients. MATERIALS AND METHOD: Forty-seven ATR patients were
      conservatively treated and entered into our study. Group 1 consisted of 23
      patients treated with partial weight bearing beginning the same day of
      conservative treatment; Group 2 consisted of 24 patients treated with non-weight
      bearing after a 4-week period. Patients were at least 18 years old and were
      followed for 12 months. Evaluation criteria were mechanism of injury, admission
      time to our clinic, complication rate, and time to return to work. Symptoms and
      physical activity levels of all patients were assessed on 6 and 12 months after
      treatment began, according to the Achilles Tendon Total Rupture Score (ATRS),
      Physical Activity Scale (PAS), and American Orthopedic Foot and Ankle Society
      (AOFAS) ankle-hindfoot score. RESULTS: Rerupture rates were rate 17.4% (4
      patients) in Group 1 and 12.5% (3 patients) in Group 2 (p = 0.81). Time to return
      to work was shorter in Group 1 compared with Group 2, but it was not
      statistically significant (p = 0.86). AOFAS, ATRS, and PAS scores at 6 and 12
      months showed no significant differences between groups (p = 0.69, p = 0.59, p =
      0.89, p = 0.77, p = 0.94, p = 0.66, respectively). CONCLUSION: This study showed
      that a well-conducted early-weight-bearing treatment has good clinical outcomes,
      with a complication rate no higher than non-weight-bearing treatment.

PMID- 25773311
TI  - Can randomized controlled trials be conducted in community social service
      settings?

PMID- 25773312
TI  - Prevalence, characteristics, and cost of self-treatment in the middle-aged and
      elderly: observations from Henan, China.

PMID- 25773313
TI  - Heavy dependent nicotine smokers--Newfound lifestyle appreciation after quitting
      successfully. Experiences from inpatient smoking cessation therapy.
AB  - OBJECTIVES: This is an evaluation of an ongoing inpatient smoking cessation
      program available in Austria and aims to show to what extent even heavy nicotine
      dependent smokers can benefit from a three-week inpatient therapy. STUDY DESIGN:
      A particular focus lies on analyzing the benefits and changes in lifestyle and
      sense of well-being. METHODS: 270 initially heavy nicotine dependent smokers are
      observed for a one year period consisting of recruitment, therapy and two post
      therapy follow-up visits; post program smokers are compared to post program ex
      smokers. RESULTS: 12 month post-therapy, 42.6% of participants are identified by
      carbon monoxide-verifications as ex-smokers, 34% as smokers and the remaining did
      not attend follow-up visits. Significant changes in lifestyle satisfaction are
      reported by ex-smokers compared to still smokers. CONCLUSIONS: Convincing heavy
      dependent nicotine smokers that significant changes in lifestyle satisfaction can
      be expected as part of a successful cessation process should lead to enough
      motivation for these individuals to seek such inpatient smoking cessation
      program.

PMID- 25773310
TI  - T cell metabolic fitness in antitumor immunity.
AB  - T cell metabolism has a central role in supporting and shaping immune responses
      and may have a key role in antitumor immunity. T cell metabolism is normally held
      under tight regulation in an immune response of glycolysis to promote effector T
      cell expansion and function. However, tumors may deplete nutrients, generate
      toxic products, or stimulate conserved negative feedback mechanisms, such as
      through Programmed Cell Death 1 (PD-1), to impair effector T cell nutrient uptake
      and metabolic fitness. In addition, regulatory T cells are favored in low glucose
      conditions and may inhibit antitumor immune responses. Here, we review how the
      tumor microenvironment modifies metabolic and functional pathways in T cells and
      how these changes may uncover new targets and challenges for cancer immunotherapy
      and treatment. 

PMID- 25773314
TI  - Prediction of true test scores from observed item scores and ancillary data.
AB  - In many educational tests which involve constructed responses, a traditional test
      score is obtained by adding together item scores obtained through holistic
      scoring by trained human raters. For example, this practice was used until 2008
      in the case of GRE((r)) General Analytical Writing and until 2009 in the case of
      TOEFL((r)) iBT Writing. With use of natural language processing, it is possible
      to obtain additional information concerning item responses from computer programs
      such as e-rater((r)). In addition, available information relevant to examinee
      performance may include scores on related tests. We suggest application of
      standard results from classical test theory to the available data to obtain best
      linear predictors of true traditional test scores. In performing such analysis,
      we require estimation of variances and covariances of measurement errors, a task
      which can be quite difficult in the case of tests with limited numbers of items
      and with multiple measurements per item. As a consequence, a new estimation
      method is suggested based on samples of examinees who have taken an assessment
      more than once. Such samples are typically not random samples of the general
      population of examinees, so that we apply statistical adjustment methods to
      obtain the needed estimated variances and covariances of measurement errors. To
      examine practical implications of the suggested methods of analysis, applications
      are made to GRE General Analytical Writing and TOEFL iBT Writing. Results
      obtained indicate that substantial improvements are possible both in terms of
      reliability of scoring and in terms of assessment reliability.

PMID- 25773315
TI  - Transcriptome analysis of the variations between autotetraploid Paulownia
      tomentosa and its diploid using high-throughput sequencing.
AB  - Timber properties of autotetraploid Paulownia tomentosa are heritable with whole
      genome duplication, but the molecular mechanisms for the predominant
      characteristics remain unclear. To illuminate the genetic basis, high-throughput
      sequencing technology was used to identify the related unigenes. 2677 unigenes
      were found to be significantly differentially expressed in autotetraploid P.
      tomentosa. In total, 30 photosynthesis-related, 21 transcription factor-related,
      and 22 lignin-related differentially expressed unigenes were detected, and the
      roles of the peroxidase in lignin biosynthesis, MYB DNA-binding proteins, and
      WRKY proteins associated with the regulation of relevant hormones are extensively
      discussed. The results provide transcriptome data that may bring a new
      perspective to explain the polyploidy mechanism in the long growth cycle of
      plants and offer some help to the future Paulownia breeding.

PMID- 25773317
TI  - Controlled by Love: The Harmful Relational Consequences of Perceived Conditional
      Positive Regard.
AB  - Research on conditional positive regard (CPR) has shown that this seemingly
      benign practice has maladaptive correlates when used by parents. However, there
      is no research on the correlates of this practice in romantic relationships or on
      the processes mediating its effects. Building on self-determination theory (Deci
      & Ryan, ), three studies tested the hypothesis that perceived CPR impairs
      relationship quality, partly because it undermines the fulfillment of the basic
      psychological needs for autonomy and relatedness. Study 1 (N = 125) examined
      perceived CPR and relationship quality across four relationship targets: mother,
      father, romantic partner, and best friend. Study 2, involving romantic partners
      (N = 142), examined whether needs fulfillment mediated the association between
      perceived CPR and relationship quality. Study 3, involving romantic dyads (N =
      85), also included partner reports on CPR. Across the three studies, CPR was
      linked with poor relationship quality between relationships, between people, and
      between dyadic partners. Moreover, results of Study 2 and Study 3 revealed that
      the inverse association between perceived CPR and relationship quality was
      mediated by dissatisfaction of autonomy but not relatedness. Despite its
      seemingly benign nature, CPR is detrimental to relationship quality, partly
      because it thwarts the basic need for autonomy.

PMID- 25773316
TI  - Transcriptome analysis reveals the potential contribution of long noncoding RNAs
      to brown adipocyte differentiation.
AB  - Brown adipose tissue (BAT) functions to dissipate energy in response to cold
      exposure or overfeeding. Counteracting obesity has been extensively considered as
      a promising target. Long noncoding RNAs (lncRNAs) are an important class of
      pervasive genes involved in a variety of biological functions. However, the
      potential biological functions of lncRNAs during mouse brown fat cell
      differentiation have not been fully understood. Here, we performed lncRNA and
      mRNA expression profile analysis using microarray technology and identified 1064
      lncRNAs with differential expression (fold change| >=4, p <= 0.01) on day 0 and
      day 8 during differentiation. Furthermore, candidate lncRNAs were characterized
      by comprehensive examination of their genomic context, gene ontology (GO)
      enrichment of their associated protein-coding genes and pathway analysis. We
      identified three lncRNAs (Gm15051, Tmem189 and Cebpd) associated with their
      flanking coding genes (Hoxa1, C/EBPbeta and C/EBPdelta), which participated in
      adipose commitment. Collectively, our findings indicated lncRNAs are involved in
      mouse BAT development and provide potential targets for obesity therapy. 

PMID- 25773318
TI  - Correlation between veno-venous anastomoses, TTTS and perinatal mortality in
      monochorionic twin pregnancies.
AB  - INTRODUCTION: The clinical significance of veno-venous (VV) anastomoses in
      monochorionic (MC) placentas remains inconclusive and controversial. The purpose
      of this study was to investigate the correlation between the presence of VV
      anastomoses and clinical outcome in a large cohort of MC twin pregnancies.
      METHODS: All MC placentas injected with colored dye from 2002 to 2014 were
      included in the study. We excluded MC pregnancies managed with fetoscopic laser
      surgery. RESULTS AND DISCUSSION: A total of 384 MC placentas were analyzed. VV
      anastomoses were detected in 27% (104/384) of MC placentas. The prevalence of
      twin-twin transfusion syndrome (TTTS) in MC placentas with VV anastomoses was
      significantly higher compared to MC placentas without VV anastomoses, 20%
      (21/104) versus 10% (29/280), respectively (P = .01). The overall perinatal
      mortality in MC twins with and without VV anastomoses was 16% versus 10%,
      respectively (P = .02). Risk factor analysis showed the presence of VV
      anastomoses was associated with perinatal mortality (P = .02; odds ratio (OR):
      1.76; 95% confidence interval (CI): 1.11-2.79), but was not an independent risk
      factor for perinatal mortality (P = .26, OR: .66; 95% CI: .33-1.35) in MC twin
      pregnancies. However, VV anastomoses was associated with and was an independent
      risk factor for TTTS (P = .00, OR: 3.59; 95% CI: 1.72-7.47). VV anastomoses
      related perinatal mortality may be due to the high rate of TTTS in MC twins with
      VV anastomoses. CONCLUSION: The presence of VV anastomoses is correlated with
      TTTS and perinatal mortality, but is not an independent risk factor for perinatal
      mortality in MC twin pregnancies.

PMID- 25773319
TI  - Small Peptides with a Big Role: Antimicrobial Peptides in the Pregnant Female
      Reproductive Tract.
AB  - There is a growing interest in the role of antimicrobial peptides (AMPs) in the
      female reproductive tract during pregnancy. This commentary highlights recent
      advances in the field including those of Itakoa and colleagues who have
      demonstrated elafin and secretory leukocyte protease inhibitor (SLPI) expression
      in cervical cells from pregnant women during pregnancy. They suggest that these
      specific AMPs may be raised in women in true preterm labour. This complements
      other studies exploring the use cervico-vaginal fluid elafin and other
      antimicrobial peptides as biomarkers to predict risk of spontaneous preterm birth
      early in pregnancy. With continued focus on the contribution and regulation of
      these important small peptides in pregnancy, the potential of AMPs as clinical
      tools for identifying women most at risk of spontaneous preterm birth should soon
      be realised. 

PMID- 25773320
TI  - Strategies for integrating mental health into schools via a multitiered system of
      support.
AB  - To fully realize the potential of mental health supports in academic settings, it
      is essential to consider how to effectively integrate the mental health and
      education systems and their respective resources, staffing, and structures.
      Historically, school mental health services have not effectively spanned a full
      continuum of care from mental health promotion to treatment, and several
      implementation and service challenges have evolved. After an overview of these
      challenges, best practices and strategies for school and community partners are
      reviewed to systematically integrate mental health interventions within a
      school's multitiered system of student support. 

PMID- 25773321
TI  - Mental health literacy in secondary schools: a Canadian approach.
AB  - "Mental health literacy is an integral component of health literacy and has been
      gaining increasing attention as an important focus globally for mental health
      interventions. In Canada, youth mental health is increasingly recognized as a key
      national health concern and has received more focused attention than ever before
      within our health system. This article outlines 2 unique homegrown initiatives to
      address youth mental health literacy within Canadian secondary schools." 

PMID- 25773322
TI  - Being present at school: implementing mindfulness in schools.
AB  - Developmentally sensitive efforts to help students learn, practice, and regularly
      use mindfulness tactics easily and readily in and beyond the classroom are
      important to help them manage future stresses. Mindfulness emphasizes consciously
      focusing the mind in the present moment, purposefully, without judgment or
      attachment. Meditation extends this to setting aside time and places to practice
      mindfulness, and additionally, yoga includes physical postures and breathing
      techniques that enhance mindfulness and meditation. Several mindfulness programs
      and techniques have been applied in schools, with positive benefits reported.
      Some elements of these programs require modifications to be sensitive to the
      developmental state of the children receiving mindfulness training. 

PMID- 25773323
TI  - Educational impacts of the social and emotional brain.
AB  - Advances in neuroscience related to social and emotional development have
      significant implications for educational practice. The human brain cannot fully
      dissociate cognitive from emotional events, and therefore educational programming
      that recognizes the importance of social-emotional development also facilitates
      academic achievement. The ideal learning environment encourages the development
      of social-emotional and academic neuronal pathways. Taking advantage of the
      emerging understanding of the developing brain offers opportunities to facilitate
      greater academic gains. 

PMID- 25773324
TI  - Safety assessment in schools: beyond risk: the role of child psychiatrists and
      other mental health professionals.
AB  - This article presents an overview of a comprehensive school safety assessment
      approach for students whose behavior raises concern about their potential for
      targeted violence. Case vignettes highlight the features of 2 youngsters who
      exemplify those seen, the comprehensive nature of the assessment, and the kind of
      recommendations that enhance a student's safety, connection, well-being; engage
      families; and share responsibility of assessing safety with the school. 

PMID- 25773325
TI  - The role of schools in substance use prevention and intervention.
AB  - Schools provide an ideal setting for screening, brief interventions, and
      outpatient treatment for substance use disorders (SUD). Individual treatment for
      SUD is effective at decreasing substance use as well as substance-related harm.
      In some contexts, rather than being helpful, group interventions can result in
      harm to participants; therefore, individual treatment may be preferred. Early
      interventions for adolescents who are using alcohol and other drugs (AOD) are
      generally effective in decreasing frequency and quantity of AOD use as well as
      decreasing risky behaviors. 

PMID- 25773326
TI  - Evidence-based interventions for adolescents with disruptive behaviors in school
      based settings.
AB  - Disruptive behaviors in the school setting can threaten the maintenance of
      optimal learning environments in schools. Challenging behaviors, such as
      defiance, hostility, and aggression, often define disruptive classroom behaviors.
      This article presents a clinical review of existing literature on interventions
      for adolescent disruptive behavior problems in school-based settings and in
      outpatient mental health settings and makes recommendations around working with
      adolescents with disruptive behaviors in school-based settings. Many types of
      interventions are effective; effective implementation is key to good results. 

PMID- 25773327
TI  - Preventing secondary traumatic stress in educators.
AB  - Teachers can be vulnerable to secondary traumatic stress (STS) because of their
      supportive role with students and potential exposure to students' experiences
      with traumas, violence, disasters, or crises. STS symptoms, similar to those
      found in posttraumatic stress disorder, include nightmares, avoidance, agitation,
      and withdrawal, and can result from secondary exposure to hearing about students'
      traumas. This article describes how STS presents, how teachers can be at risk,
      and how STS can manifest in schools. A US Department of Education training
      program is presented, and thoughts on future directions are discussed. 

PMID- 25773328
TI  - School-based approaches to reducing the duration of untreated psychosis.
AB  - Students with emerging psychosis often experience delays in diagnosis and
      treatment that impact mental health and academic outcomes. School systems have
      tremendous potential to improve early identification and treatment of adolescent
      psychosis. As a community-based resource, schools can support outreach,
      education, and screening for adolescents with psychosis and engage identified
      students and their families for treatment. The concept of duration of untreated
      psychosis (DUP; the gap between symptom onset and treatment initiation) in
      adolescent psychosis and the potential role of schools in reducing DUP are
      reviewed. Future directions for clinical care and research needed to support
      school-based interventions are proposed. 

PMID- 25773329
TI  - School-based suicide prevention: content, process, and the role of trusted adults
      and peers.
AB  - Suicide is a leading cause of preventable death in youth, and numerous curricula
      and other prevention and intervention programs have been developed in the last 15
      years. Comprehensive suicide prevention planning should include the 4 components
      of health promotion, prevention/education, intervention, and postvention. School
      based suicide prevention and mental health education programs have become more
      common as an efficient and cost-effective way to reach youth. Process
      considerations that are based on the principles of therapeutic engagement with
      patients and families can provide mental health professionals with strategies
      that can assist education professionals, students, and the larger school
      community simultaneously. 

PMID- 25773330
TI  - Supporting the transition from inpatient hospitalization to school.
AB  - The School Transition Program (STP) is a 3-month intervention developed to
      address the unique needs of youth transitioning back to school from an inpatient
      psychiatric hospitalization. The STP focuses on promoting communication across
      school, home, and hospital. It includes psychoeducation, emotional support for
      caregivers, and the creation of transition plans in collaboration with school
      staff and families. Matching interventions to the academic, social,
      emotional/behavioral needs of these youth and increasing support to their
      caregivers has the potential to ease stress, reduce challenges and promote
      success during and after the transition period. 

PMID- 25773331
TI  - Engaging youth and families in school mental health services.
AB  - In this article, an overview is provided of strategies to engage youth and their
      families in school mental health (SMH) services throughout the course of
      treatment. Resources are outlined to help SMH providers determine which
      strategies are most suitable for youth and their families, based on outcomes
      desired, barriers to engagement, and stage of treatment. Four case vignettes are
      presented to describe implementation of these strategies. 

PMID- 25773332
TI  - Implementing clinical outcomes assessment in everyday school mental health
      practice.
AB  - Evidence-based assessment (EBA) has been shown to improve clinical outcomes, but
      this practice is frequently not implemented in school mental health practice.
      This article reviews potential barriers to implementation and offers practical
      strategies for addressing these challenges. Several valid and reliable tools for
      assessment are reviewed, and information is provided on clinical use. Case
      examples of EBA implementation in school mental health settings are provided to
      illustrate how these tools can be used in everyday practice by school mental
      health clinicians. 

PMID- 25773333
TI  - The evolution of a school behavioral health model in the US Army.
AB  - The US Army has developed an innovative School Behavioral Health (SBH) program,
      part of the Child and Family Behavioral Health System, a collaborative,
      consultative behavioral health care model that includes SBH, standardized
      training of primary care providers in treatment of common behavioral health
      problems, use of tele-consultation/tele-behavioral health, optimizing community
      outreach services, and integration with other related behavioral health services.
      In this article, the needs of military children, adolescents, and families are
      reviewed, a history of this initiative is presented, key themes are discussed,
      and next steps in advancing this evolving, innovative system of health care
      featuring SBH are described. 

PMID- 25773334
TI  - Integrating mental health into schools to support student success.

PMID- 25773335
TI  - Characteristics of bacteremia in pediatric oncology patients based on pathogen
      classification as associated with the gastrointestinal mucosa or skin.
AB  - Factors favoring blood stream infections associated with gastrointestinal mucosa
      versus skin organisms were explored. An observed difference was attributable to
      bacteremia from oral flora in patients with acute myelogenous leukemia or
      mucositis. Our data do not support the conclusion that isolation of enteric Gram
      negatives is unrelated to the central catheter.

PMID- 25773336
TI  - The structure, including stereochemistry, of levorin A1.

PMID- 25773337
TI  - Biodegradation of an endocrine-disrupting chemical di-n-butyl phthalate by newly
      isolated Camelimonas sp. and enzymatic properties of its hydrolase.
AB  - An aerobic bacterial strain M11 capable of degrading dibutyl phthalate (DBP) was
      isolated and identified as Camelimonas sp. This strain could not grow on dialkyl
      phthalates, including dimethyl, diethyl, dipropyl, dibutyl and dipentyl
      phthalate, but suspensions of cells could transform these compounds to phthalate
      via corresponding monoalkyl phthalates. The degradation kinetics of DBP was best
      fitted by first-order kinetic equation. During growth in Brucella Selective
      Medium, M11 produced the high amounts of non-DBP-induced intracellular hydrolase
      in the stationary phase. The DBP hydrolase gene of M11 was cloned, and the
      recombinant DBP hydrolase had a high optimum degradation temperature (50  degrees
      C), and a wide range of pH and temperature stability. 

PMID- 25773339
TI  - Near infrared and skin impedance spectroscopy - a possible support in the
      diagnostic process of skin tumours in primary health care.
AB  - BACKGROUND/PURPOSE: The global incidence of skin cancer has increased drastically
      in recent decades, especially in Australia and Northern Europe. Early detection
      is crucial for good prognosis and high survival rates. In general, primary care
      physicians have considerably lower sensitivity and specificity rates for
      detection of skin cancer, compared to dermatologists. A probable main reason for
      this is that current diagnostic tools are subjective in nature, and therefore
      diagnostic skills highly depend on experience. Illustratively, in Sweden,
      approximately 155 500 benign skin lesions are excised unnecessarily every year.
      An objective instrument, added to the clinical examination, might improve the
      diagnostic accuracy, and thus promote earlier detection of malignant skin
      tumours, as well as reduce medical costs associated with unnecessary biopsies and
      excisions. The general aim of this study was to investigate the usefulness of the
      combination of near infrared (NIR) and skin impedance spectroscopy as a
      supportive tool in the diagnosis and evaluation of skin tumours in primary health
      care. METHODS: Near infrared and skin impedance data were collected by performing
      measurements on suspect malignant, premalignant and benign tumours in the skin of
      patients seeking primary health care for skin tumour evaluation. The obtained
      data were analysed using multivariate analysis and compared with the diagnosis
      received by the conventional diagnostic process. RESULTS: The observed
      sensitivity and specificity rates were both 100%, when discriminating malignant
      and premalignant skin tumours from benign skin tumours, and the observed
      sensitivity and specificity for separating malignant skin tumours from
      premalignant and benign skin tumours were also 100%, respectively. CONCLUSION:
      The results of this study indicate that the NIR and skin impedance spectroscopy
      may be a useful supportive tool for the general practitioner in the diagnosis and
      evaluation of skin tumours in primary health care, as a complement to the visual
      assessment.

PMID- 25773340
TI  - Central nervous system-specific alterations in the tryptophan metabolism in the 3
      nitropropionic acid model of Huntington's disease.
AB  - Experiments on human samples and on genetic animal models of Huntington's disease
      (HD) suggest that a number of neuroactive metabolites in the kynurenine (KYN)
      pathway (KP) of the tryptophan (TRP) catabolism may play a role in the
      development of HD. Our goal in this study was to assess the concentrations of
      TRP, KYN, kynurenic acid and 3-hydroxykynurenine (3-OHK) in the serum and brain
      of 5-month-old C57Bl/6 mice in the widely used 3-nitropropionic acid (3-NP) toxin
      model of HD. We additionally investigated the behavioral changes through open
      field, rotarod and Y-maze tests. Our findings revealed an increased TRP
      catabolism via the KP as reflected by elevated KYN/TRP ratios in the striatum,
      hippocampus, cerebellum and brainstem. As regards the other examined metabolites
      of KP, we found only a significant decrease in the 3-OHK level in the cerebellum
      of the 3-NP-treated mice. The open-field and rotarod tests demonstrated that
      treatment with 3-NP resulted in a reduced motor ability, though this had almost
      totally disappeared a week after the last injection, similarly as observed
      previously in most murine 3-NP studies. The relevance of the alterations observed
      in our biochemical and behavioral analyses is discussed. We propose that the
      identified biochemical alterations could serve as applicable therapeutic
      endpoints in studies of drug effects on delayed-type neurodegeneration in a
      relatively fast and cost-effective toxin model of HD.

PMID- 25773341
TI  - Extra (non-contingent) food does not affect behavioral tolerance to d
      amphetamine's rate-decreasing effects.
AB  - Tolerance refers to the diminished effect of a drug following its repeated
      administration such that a larger dose is needed to obtain the initial effect.
      Tolerance to a drug's effects on operant behavior is more likely to develop when
      initial drug administration results in a loss of reinforcement. It remains
      unknown how offsetting loss of reinforcement influences the development of
      tolerance. Providing extra (non-contingent) food pellets was hypothesized to
      impede the development of tolerance to effects of a repeatedly administered dose
      of d-amphetamine that reduced the number of food pellets earned by rats. A
      multiple schedule with two variable-interval (VI) 60-s components resulting in
      food delivery was used to maintain lever pressing. Extra food pellets were
      provided in one of those components according to a variable-time (VT) 120-s or a
      VT 30-s schedule for separate groups of rats (n=6 for each group). Effects of d
      amphetamine (0.1-3.0mg/kg) were tested before (acute) and during (chronic)
      injections (45days) of an individually selected, repeatedly administered dose
      that reduced the number of food pellets earned by at least 50% compared to when
      saline was tested acutely. There was a dose-dependent decrease in lever-press
      rates and food pellets earned. The development of tolerance was quantified by
      dividing the area-under-the-curve (AUC) of the chronic dose-effect function by
      the AUC of the acute dose-effect function. Tolerance developed to a similar
      extent in components with and without extra food pellets for rats in both groups.
      These results indicate that offsetting reinforcement loss, at least as studied
      here, did not differentially affect tolerance development.

PMID- 25773342
TI  - Systemic therapy for advanced pancreatic cancer: individualising cytotoxic
      therapy.
AB  - INTRODUCTION: Pancreatic cancer is an aggressive solid tumour associated with a
      high risk of local invasion and metastatic spread. In the absence of validated
      screening approaches, many patients present with advanced, incurable disease.
      Despite advances in treatment, the prognosis for patients with advanced
      pancreatic cancer remains poor. The benefits of surgical resection and radiation
      are unproven in this setting and, as patients generally present with distant
      metastases, systemic therapy forms the mainstay of treatment. The importance of
      selecting the optimal cytotoxic therapy remains to be critical to improving
      outcome and retaining quality of life. This review sets out to compare the
      current therapies available for advanced pancreatic cancer. AREAS COVERED: This
      review examines the evolution of the systemic management of advanced pancreatic
      cancer, with a particular focus on the landmark Phase III trials identified from
      an extensive PubMed and Google scholar literature search. The article summarises
      the cytotoxic agents in use and the results of two decades of clinical trials to
      culminate in an almost doubling of survival in clinical trials. EXPERT OPINION:
      In the concluding expert opinion, the challenges interpreting and translating
      trial results into clinical practice are discussed, where patients are often
      older and of worse performance status. In the future, novel biomarkers might be
      used to tailor therapy.

PMID- 25773343
TI  - Role of hydrogen sulfide within the dorsal motor nucleus of the vagus in the
      control of gastric function in rats.
AB  - BACKGROUND: Hydrogen sulfide (H2 S) is a gaseous messenger and serves as an
      important neuromodulator in the central nervous system. This study aimed to
      clarify the role of H2 S within the dorsal motor nucleus of the vagus (DMV) in
      the control of gastric function in rats. METHODS: Cystathionine beta-synthetase
      (CBS) is an important generator of endogenous H2 S in the brain. We investigated
      the distribution of CBS in the DMV using immunohistochemical method, and the
      effects of H2 S on gastric motility and on gastric acid secretion. KEY RESULTS:
      CBS-immunoreactive (IR) neurons were detected in the rostral, intermediate and
      caudal DMV, with the highest number of CBS-IR neurons in the caudal DMV, and the
      lowest in the intermediate DMV. We also found that microinjection of the
      exogenous H2 S donor NaHS (0.04 and 0.08 mol/L; 0.1 MUL; n = 6; p < 0.05) into
      the DMV significantly inhibited gastric motility with a dose-dependent trend, and
      promoted gastric acid secretion in Wistar rats. Microinjection of the same volume
      of physiological saline (PS; 0.1 MUL, n = 6, p > 0.05) at the same location did
      not noticeably change gastric motility and acid secretion. CONCLUSIONS &
      INFERENCES: The data from these experiments suggest that the CBS that produces H2
      S is present in the DMV, and microinjection of NaHS into the DMV inhibited
      gastric motility and enhanced gastric acid secretion in rats.

PMID- 25773344
TI  - Reply: To PMID 25502967.

PMID- 25773345
TI  - Postoperative changes in serum CO2 as an indicator of postoperative complications
      after radical cystectomy.
AB  - The purpose of this article was to review the relationship of postoperative CO2
      levels to the risk of complications after radical cystectomy. In this review, we
      summarize the existing body of literature on the topic as well as metabolic
      complications after urinary diversion. Currently, there are no studies that
      specifically examine CO2 levels in the context of complications after radical
      cystectomy; therefore, we also present our own institutional data which
      demonstrate that a drop in postoperative CO2 levels is highly predictive of
      complications, the most common of which is failure to thrive. These data indicate
      that significant changes in CO2 levels prior to discharge after a radical
      cystectomy may be a harbinger of forthcoming complications. 

PMID- 25773346
TI  - Percutaneous stone removal: new approaches to access and imaging.
AB  - Percutaneous renal access and removal of large renal calculi was first described
      nearly 40 years ago and has since become the gold standard in management of large
      and complex renal calculi. In this same time period, technological and medical
      advances have allowed this procedure to develop in improved efficacy and
      morbidity. The following review offers an update to new approaches to
      percutaneous renal access and imaging in the management of large and complex
      renal calculi. 

PMID- 25773347
TI  - Guidance on patient consultation. Current evidence for prostate-specific antigen
      screening in healthy men and treatment options for men with proven localised
      prostate cancer.
AB  - The main objective of this review is to summarise, for primary and secondary care
      doctors, the management options and current supporting evidence for clinically
      localised prostate cancer. We review all aspects of management including current
      guidelines on early cancer detection and the importance of informed consent on
      PSA-based screening and assess the most common treatment options and the evidence
      for managing patients with low-, medium-, and high-risk disease. 

PMID- 25773349
TI  - Organ-confined prostate cancer: are we moving towards more or less radical
      surgical intervention?
AB  - Treatment possibilities for clinically localised prostate cancer include radical
      prostatectomy (RP), external beam radiotherapy, brachytherapy, focal therapy and
      active surveillance. Conflicting and methodologically flawed observational data
      from the last two decades have led to uncertainty as to the best oncological
      option. However, recently, there has been a series of high-quality studies that
      point to disease specific and overall survival advantages for those men
      undergoing RP. This article reviews the latest evidence and argues that at the
      current time, RP must be considered the gold standard treatment for the majority
      of men with clinically localised prostate cancer. 

PMID- 25773348
TI  - Perioperative strategies to reduce postoperative complications after radical
      cystectomy.
AB  - Radical cystectomy with creation of urinary diversion is the standard treatment
      for muscle-invasive urothelial carcinoma of the bladder. Despite advances in
      perioperative care, radical cystectomy is associated with significant morbidity.
      Reduction in perioperative morbidity and mortality remains a primary focus of
      bladder cancer outcome improvement. A number of evidence-based approaches to
      perioperative care have been proposed to reduce the overall burden of
      complications associated with radical cystectomy. Herein, we highlight and review
      recent and evolving evidence-based strategies to minimize the morbidity
      associated with surgical management of muscle-invasive bladder cancer. 

PMID- 25773350
TI  - Lymph node staging in prostate cancer.
AB  - Nodal staging is important in prostate cancer treatment. While surgical lymph
      node dissection is the classic method of determining whether lymph nodes harbor
      malignancy, this is a very invasive technique. Current noninvasive approaches to
      identifying malignant lymph nodes are limited. Conventional imaging methods rely
      on size and morphology of lymph nodes and have notoriously low sensitivity for
      detecting malignant nodes. New imaging techniques such as targeted positron
      emission tomography (PET) imaging and magnetic resonance lymphography (MRL) with
      iron oxide particles are promising for nodal staging of prostate cancer. In this
      review, the strengths and limitations of imaging techniques for lymph node
      staging of prostate cancer are discussed. 

PMID- 25773352
TI  - Cysteine dietary supplementation reverses the decrease in mitochondrial ROS
      production at complex I induced by methionine restriction.
AB  - It has been described that dietary cysteine reverses many of the beneficial
      changes induced by methionine restriction in aging rodents. In this investigation
      male Wistar rats were subjected to diets low in methionine, supplemented with
      cysteine, or simultaneously low in methionine and supplemented with cysteine. The
      results obtained in liver showed that cysteine supplementation reverses the
      decrease in mitochondrial ROS generation induced by methionine restriction at
      complex I. Methionine restriction also decreased various markers of oxidative and
      non-oxidative stress on mitochondrial proteins which were not reversed by
      cysteine. Instead, cysteine supplementation also lowered protein damage in
      association with decreases in mTOR activation. The results of the present study
      add the decrease in mitochondrial ROS production to the various beneficial
      changes induced by methionine restriction that are reversed by cysteine dietary
      supplementation. 

PMID- 25773353
TI  - A benchmarking program to reduce red blood cell outdating: implementation,
      evaluation, and a conceptual framework.
AB  - BACKGROUND: Benchmarking is a quality improvement tool that compares an
      organization's performance to that of its peers for selected indicators, to
      improve practice. STUDY DESIGN AND METHODS: Processes to develop evidence-based
      benchmarks for red blood cell (RBC) outdating in Ontario hospitals, based on RBC
      hospital disposition data from Canadian Blood Services, have been previously
      reported. These benchmarks were implemented in 160 hospitals provincewide with a
      multifaceted approach, which included hospital education, inventory management
      tools and resources, summaries of best practice recommendations, recognition of
      high-performing sites, and audit tools on the Transfusion Ontario website
      (http://transfusionontario.org). In this study we describe the implementation
      process and the impact of the benchmarking program on RBC outdating. A conceptual
      framework for continuous quality improvement of a benchmarking program was also
      developed. RESULTS: The RBC outdating rate for all hospitals trended downward
      continuously from April 2006 to February 2012, irrespective of hospitals'
      transfusion rates or their distance from the blood supplier. The highest annual
      outdating rate was 2.82%, at the beginning of the observation period. Each year
      brought further reductions, with a nadir outdating rate of 1.02% achieved in
      2011. The key elements of the successful benchmarking strategy included dynamic
      targets, a comprehensive and evidence-based implementation strategy, ongoing
      information sharing, and a robust data system to track information. CONCLUSION:
      The Ontario benchmarking program for RBC outdating resulted in continuous and
      sustained quality improvement. Our conceptual iterative framework for
      benchmarking provides a guide for institutions implementing a benchmarking
      program.

PMID- 25773351
TI  - Polygenic risk of Parkinson disease is correlated with disease age at onset.
AB  - OBJECTIVE: We have investigated the polygenic architecture of Parkinson disease
      (PD) and have also explored the potential relationship between an individual's
      polygenic risk score and their disease age at onset. METHODS: This study used
      genotypic data from 4,294 cases and 10,340 controls obtained from the meta
      analysis of PD genome-wide association studies. Polygenic score analysis was
      performed as previously described by the International Schizophrenia Consortium,
      testing whether the polygenic score alleles identified in 1 association study
      were significantly enriched in the cases relative to the controls of 3
      independent studies. Linear regression was used to investigate the relationship
      between an individual's polygenic score for PD risk alleles and disease age at
      onset. RESULTS: Our polygenic score analysis has identified significant evidence
      for a polygenic component enriched in the cases of each of 3 independent PD
      genome-wide association cohorts (minimum p = 3.76 * 10(-6) ). Further analysis
      identified compelling evidence that the average polygenic score in patients with
      an early disease age at onset was significantly higher than in those with a late
      age at onset (p = 0.00014). INTERPRETATION: This provides strong support for a
      large polygenic contribution to the overall heritable risk of PD and also
      suggests that early onset forms of the illness are not exclusively caused by
      highly penetrant Mendelian mutations, but can also be contributed to by an
      accumulation of common polygenic alleles with relatively low effect sizes.

PMID- 25773354
TI  - Dose-exposure proportionality of a novel recombinant follicle-stimulating hormone
      (rFSH), FE 999049, derived from a human cell line, with comparison between
      Caucasian and Japanese women after subcutaneous administration.
AB  - BACKGROUND AND OBJECTIVES: FE 999049 is a novel recombinant follicle-stimulating
      hormone (rFSH) preparation expressed by a human cell line (PER.C6((r))), in
      contrast to existing rFSH preparations expressed by Chinese hamster ovary (CHO)
      cell lines. Since the individual dose of rFSH may be altered depending on the
      response in women undergoing assisted reproductive technologies, knowledge on the
      dose-exposure linearity and proportionality is important. The purpose of these
      studies was to investigate the dose-exposure linearity and proportionality
      properties of FE 999049 with a comparison between Caucasian and Japanese women.
      This is the first study in Japanese women regarding pharmacokinetics of rFSH.
      METHODS: Forty-eight Caucasian and 31 Japanese healthy women of reproductive age
      were pituitary down-regulated to suppress endogenous FSH. Following single
      subcutaneous administration of 37.5, 75, 150, 225, or 450 IU (Steelman-Pohley
      assay), the serum FSH concentration was followed over 10 days. RESULTS: The dose
      dependent pharmacokinetic parameters of FE 999049, area under the serum
      concentration-time curve (AUC) and maximum serum concentration (C max), showed
      dose-exposure linearity and proportionality over 150-450 IU in Caucasian women,
      the dose interval available for analysis, and 75-450 IU in Japanese women, which
      was the dose interval investigated. Comparison between Caucasian and Japanese
      women showed no differences between the populations. The dose-independent
      parameters were similar over all doses in both populations. FE 999049 was safe
      and well tolerated at all doses in both populations with few, mostly mild,
      adverse events. CONCLUSION: The results demonstrate dose-exposure proportionality
      and a predictable dose-dependent exposure of FE 999049, with no differences in
      Caucasian and Japanese women of reproductive age.

PMID- 25773268
TI  - Long-term use of ticagrelor in patients with prior myocardial infarction.
AB  - BACKGROUND: The potential benefit of dual antiplatelet therapy beyond 1 year
      after a myocardial infarction has not been established. We investigated the
      efficacy and safety of ticagrelor, a P2Y12 receptor antagonist with established
      efficacy after an acute coronary syndrome, in this context. METHODS: We randomly
      assigned, in a double-blind 1:1:1 fashion, 21,162 patients who had had a
      myocardial infarction 1 to 3 years earlier to ticagrelor at a dose of 90 mg twice
      daily, ticagrelor at a dose of 60 mg twice daily, or placebo. All the patients
      were to receive low-dose aspirin and were followed for a median of 33 months. The
      primary efficacy end point was the composite of cardiovascular death, myocardial
      infarction, or stroke. The primary safety end point was Thrombolysis in
      Myocardial Infarction (TIMI) major bleeding. RESULTS: The two ticagrelor doses
      each reduced, as compared with placebo, the rate of the primary efficacy end
      point, with Kaplan-Meier rates at 3 years of 7.85% in the group that received 90
      mg of ticagrelor twice daily, 7.77% in the group that received 60 mg of
      ticagrelor twice daily, and 9.04% in the placebo group (hazard ratio for 90 mg of
      ticagrelor vs. placebo, 0.85; 95% confidence interval [CI], 0.75 to 0.96;
      P=0.008; hazard ratio for 60 mg of ticagrelor vs. placebo, 0.84; 95% CI, 0.74 to
      0.95; P=0.004). Rates of TIMI major bleeding were higher with ticagrelor (2.60%
      with 90 mg and 2.30% with 60 mg) than with placebo (1.06%) (P<0.001 for each dose
      vs. placebo); the rates of intracranial hemorrhage or fatal bleeding in the three
      groups were 0.63%, 0.71%, and 0.60%, respectively. CONCLUSIONS: In patients with
      a myocardial infarction more than 1 year previously, treatment with ticagrelor
      significantly reduced the risk of cardiovascular death, myocardial infarction, or
      stroke and increased the risk of major bleeding. (Funded by AstraZeneca; PEGASUS
      TIMI 54 ClinicalTrials.gov number, NCT01225562.).

PMID- 25773355
TI  - Maternal total caffeine intake, mainly from Japanese and Chinese tea, during
      pregnancy was associated with risk of preterm birth: the Osaka Maternal and Child
      Health Study.
AB  - The relation of maternal caffeine intake with birth outcomes is still
      inconclusive and has not been examined in Japan, where the sources of caffeine
      intake are different from those in Western countries. We hypothesized that
      maternal consumption of total caffeine and culture-specific major sources of
      caffeine would be associated with birth outcomes among Japanese pregnant. The
      study subjects were 858 Japanese women who delivered singleton infants. Maternal
      diet during pregnancy was assessed using a validated, self-administered diet
      history questionnaire. Birth outcomes considered were low birth weight (LBW;
      <2500 g), preterm birth (PTB; <37 weeks of gestation), and small for gestational
      age (SGA; <10th percentile). The main caffeine sources were Japanese and Chinese
      tea (73.5%), coffee (14.3%), black tea (6.6%), and soft drinks (3.5%). After
      controlling for confounders, maternal total caffeine intake during pregnancy was
      significantly associated with an increased risk of PTB (odds ratio per 100 mg/d
      caffeine increase, 1.28; 95% confidence interval, 1.03-1.58; P for trend = .03).
      However, no evident relationships were observed between total caffeine intake and
      risk of LBW or SGA. As for caffeine sources, higher Japanese and Chinese tea
      consumption was associated with an increased risk of PTB (odds ratio per 1 cup/d
      increase, 1.14; 95% confidence interval, 1.00-1.30; P for trend = .04), but not
      LBW or SGA. There were no associations between consumption of the other beverages
      examined and birth outcomes. In conclusion, this prospective birth cohort in
      Japan suggests that higher maternal total caffeine intake, mainly in the form of
      Japanese and Chinese tea, during pregnancy is associated with a greater risk of
      PTB. 

PMID- 25773356
TI  - Exploring the protein stability landscape: Bacillus subtilis lipase A as a model
      for detergent tolerance.
AB  - A systematic study was conducted with Bacillus subtilis lipase A (BSLA) to
      determine the effect of every single amino acid substitution on detergent
      tolerance. BSLA is a minimal alpha/beta-hydrolase of 181 amino acids with a known
      crystal structure. It can be expressed in Escherichia coli and is biochemically
      well characterized. Site saturation mutagenesis resulted in a library of 3439
      variants, each with a single amino acid exchange as confirmed by DNA sequencing.
      The library was tested against four detergents, namely SDS, CTAB, Tween 80, and
      sulfobetaine. Surface remodeling emerged as an effective engineering strategy to
      increase tolerance towards detergents. Amino acid residues that significantly
      affect the tolerance for each of the four detergents were identified. In summary,
      this systematic analysis provides an experimental dataset to help derive novel
      protein engineering strategies as well as to direct modeling efforts. 

PMID- 25773360
TI  - Discussion of "On Bayesian Estimation of Marginal Structural Models".

PMID- 25773361
TI  - Photocatalytic reduction of CO2 with H2O to CH4 on Cu(I) supported TiO2
      nanosheets with defective {001} facets.
AB  - Highly dispersed Cu2O clusters loaded on TiO2 nanosheets with dominant exposed
      {001} facets are prepared by a hydrothermal treatment followed by
      photodeposition. The physicochemical properties of the as-prepared samples are
      characterized carefully. The deposition position and chemical state of the Cu2O
      clusters are characterized by X-ray diffraction, transmission electron
      microscopy, UV-vis diffuse reflectance spectroscopy, EPR spectroscopy, and in
      situ CO-adsorbed FTIR spectroscopy, respectively. The results show that in situ
      Cu deposition leads to in situ formation of abundant oxygen vacancies (Vo) on the
      surface of the TiO2 nanosheets. Interestingly, the co-existence of Vo and Cu2O
      clusters could promote the photoactivity of CO2 reduction efficiently. The
      surface Vo play a significant role in the reduction of CO2. Meanwhile, the
      deposited Cu(I) species serve also as active sites for the formation of CH4, and
      then protect CH4 from degradation by generated oxidation species. For the
      photoreduction of CO2 to CH4, it is found that the content level of Cu2O has a
      significant influence on the activity. Cu-TiO2-1.0 shows the highest
      photocatalytic activity, which is over 30 times higher than that of the parent
      TiO2. This great enhancement of photocatalytic activity may be contributed by
      high CO2 adsorption capacity, high electron mobility, and high concentration of
      Vo. However, the effect of the surface area of the samples on the activity is
      negligible. All of this evidence is obtained by CO2-sorption, electrochemistry,
      in situ FTIR spectroscopy, in situ ERP techniques, etc. The reaction
      intermediates are detected by in situ FTIR spectroscopy. Finally, a probable
      mechanism is proposed based on the experimental results. It is hoped that our
      work could render one of the most effective strategies to achieve advanced
      properties over photofunctional materials for solar energy conversion of CO2.

PMID- 25773363
TI  - Ruthenium-catalyzed aerobic oxidative decarboxylation of amino acids: a green,
      zero-waste route to biobased nitriles.
AB  - Oxidative decarboxylation of amino acids into nitriles was performed using
      molecular oxygen as terminal oxidant and a heterogeneous ruthenium hydroxide
      based catalyst. A range of amino acids was oxidized in very good yield, using
      water as the solvent. 

PMID- 25773359
TI  - Design and optimization of topical methotrexate loaded niosomes for enhanced
      management of psoriasis: application of Box-Behnken design, in-vitro evaluation
      and in-vivo skin deposition study.
AB  - Psoriasis, a skin disorder characterized by impaired epidermal differentiation,
      is regularly treated by systemic methotrexate (MTX), an effective cytotoxic drug
      but with numerous side effects. The aim of this work was to design topical MTX
      loaded niosomes for management of psoriasis to avoid systemic toxicity. To
      achieve this goal, MTX niosomes were prepared by thin film hydration technique. A
      Box-Behnken (BB) design, using Design-Expert((r)) software, was employed to
      statistically optimize formulation variables. Three independent variables were
      evaluated: MTX concentration in hydration medium (X1), total weight of niosomal
      components (X2) and surfactant: cholesterol ratio (X3). The encapsulation
      efficiency percent (Y1: EE%) and particle size (Y2: PS) were selected as
      dependent variables. The optimal formulation (F12) displayed spherical morphology
      under transmission electron microscopy (TEM), optimum particle size of 1375.00 nm
      and high EE% of 78.66%. In-vivo skin deposition study showed that the highest
      value of percentage drug deposited (22.45%) and AUC0-10 (1.15 mg.h/cm(2)) of MTX
      from niosomes were significantly greater than that of drug solution (13.87% and
      0.49 mg.h/cm(2), respectively). Moreover, in-vivo histopathological studies
      confirmed safety of topically applied niosomes. Concisely, the results showed
      that targeted MTX delivery might be achieved using topically applied niosomes for
      enhanced treatment of psoriasis.

PMID- 25773362
TI  - Peripheral retinal function assessed with 30-Hz flicker seems to improve after
      treatment with Lucentis in patients with diabetic macular oedema.
AB  - PURPOSE: To evaluate the influence of ranibizumab on the multifocal
      electroretinogram (Mf-ERG), full-field electroretinogram (Ff-ERG) and optical
      coherence tomography (OCT) in diabetic eyes (n = 20) with macular oedema.
      METHODS: In 20 eyes (20 diabetic subjects) with no or background diabetic
      retinopathy and macular oedema (age 65.7 +/- 9.8 years, duration 16.5 +/- 10.0
      years), the change in ETDRS letters, Mf-ERG, Ff-ERG and OCT was analysed, at
      baseline, 4 weeks after the first injection, (just before the second injection),
      and 4 weeks after the last injection with ranibizumab. RESULTS: From baseline,
      mean BCVA improved from 64.0 +/- 10.0 ETDRS letters to 75.0 +/- 7.3 ETDRS letters
      (p = 0.005) 1 month after the last injection. Mean OCT thickness reduced after
      the first injection from 418 +/- 117 to 311 +/- 126 um; (p = 0.001) and to 302 +/
      74 um after the third injection. Mf-ERG demonstrated in the innermost three
      rings a shorter implicit time after the first injection with p values of 0.002,
      0.005 and 0.017, respectively. After the third injection, implicit time was
      prolonged to almost the original levels. Cone implicit time with 30-Hz flicker
      improved significantly between baseline (35.5 +/- 3.6 ms) and final follow-up
      (34.6 +/- 3.1 ms) (p = 0.04). DISCUSSION: Though the central retinal thickness
      was reduced after three injections of ranibizumab and the subjects gained a mean
      of 11 ETDRS letters, there was no significant change in amplitude or implicit
      time in Mf-ERG. The shortened 30-Hz flicker implicit time might imply that
      ranibizumab has no negative impact on the entire peripheral cone function, but
      can improve it instead.

PMID- 25773358
TI  - Introduction of a nomogram for predicting adverse pregnancy outcomes based on
      maternal serum markers in the quad screen test.
AB  - PURPOSE: The aim of this study was to develop a nomogram that can calculate a
      total score, derived from each serum marker in the quad screen test, for
      systematically predicting adverse pregnancy outcomes (APOs). METHODS: We
      retrospectively reviewed 3684 singleton pregnant women who underwent a quad
      screen test and gave birth at a single medical centre from January 2005 to
      December 2010. The serum marker data from the quad screen test and pregnancy
      outcomes were used to construct logistic regression models for predicting the
      risks of APOs. APO was defined as the presence of at least one of the following:
      preeclampsia, preterm delivery before 34 weeks of gestation, small for
      gestational age, foetal loss, and foetal demise. A graphic nomogram was generated
      to represent the scoring model using the regression coefficient of each serum
      marker. RESULTS: A nomogram for the prediction of APOs using each serum marker in
      the quad test was developed based on the logistic regression analysis. The
      positive predictive values for the subsequent development of an APO were ascended
      stepwise as the calculated score increases. The area under the receiver operating
      characteristic curve of this score for the prediction of APO was 0.596 (95 %
      confidence interval 0.569-0.623). CONCLUSIONS: We here introduced a nomogram for
      stratifying the risk of APOs in patients with abnormal serum markers in the quad
      screen test. Although the validity of the nomogram is too weak to be used in
      clinical routine, but it may provide additional information for practitioners
      counselling pregnant women and for predicting APOs.

PMID- 25773357
TI  - Hysterectomy in very obese and morbidly obese patients: a systematic review with
      cumulative analysis of comparative studies.
AB  - PURPOSE: Some studies suggest that also regarding the patient with a body mass
      index (BMI) >=35 kg/m(2) the minimally invasive approach to hysterectomy is
      superior. However, current practice and research on the preference of
      gynaecologists still show that the rate of abdominal hysterectomy (AH) increases
      as the BMI increases. A systematic review with cumulative analysis of comparative
      studies was performed to evaluate the outcomes of AH, laparoscopic hysterectomy
      (LH) and vaginal hysterectomy (VH) in very obese and morbidly obese patients (BMI
      >=35 kg/m(2)). METHODS: PubMed and EMBASE were searched for records on AH, LH and
      VH for benign indications or (early stage) malignancy through October 2014.
      Included studies were graded on level of evidence. Studies with a comparative
      design were pooled in a cumulative analysis. RESULTS: Two randomized controlled
      trials, seven prospective studies and 14 retrospective studies were included
      (2232 patients; 1058 AHs, 959 LHs, and 215 VHs). The cumulative analysis
      identified that, compared to LH, AH was associated with more wound dehiscence
      [risk ratio (RR) 2.58, 95 % confidence interval (CI) 1.71-3.90; P = 0.000], more
      wound infection (RR 4.36, 95 % CI 2.79-6.80; P = 0.000), and longer hospital
      admission (mean difference 2.9 days, 95 % CI 1.96-3.74; P = 0.000). The pooled
      conversion rate was 10.6 %. Compared to AH, VH was associated with similar
      advantages as LH. CONCLUSIONS: Compared to AH, both LH and VH are associated with
      fewer postoperative complications and shorter length of hospital stay. Therefore,
      the feasibility of LH and VH should be considered prior the abdominal approach to
      hysterectomy in very obese and morbidly obese patients.

PMID- 25773364
TI  - PAR-6, but not E-cadherin and beta-integrin, is necessary for epithelial
      polarization in C. elegans.
AB  - Cell polarity is a fundamental characteristic of epithelial cells. Classical cell
      biological studies have suggested that establishment and orientation of polarized
      epithelia depend on outside-in cues that derive from interactions with either
      neighboring cells or the substratum (Akhtar and Streuli, 2013; Chen and Zhang,
      2013; Chung and Andrew, 2008; McNeill et al., 1990; Nejsum and Nelson, 2007;
      Nelson et al., 2013; Ojakian and Schwimmer, 1994; Wang et al., 1990; Yu et al.,
      2005). This paradigm has been challenged by examples of epithelia generated in
      the absence of molecules that mediate cell-cell or cell-matrix interactions,
      notably E-cadherin and integrins (Baas et al., 2004; Choi et al., 2013; Costa et
      al., 1998; Harris and Peifer, 2004; Raich et al., 1999; Roote and Zusman, 1995;
      Vestweber et al., 1985; Williams and Waterston, 1994; Wu et al., 2009). Here we
      explore an alternative hypothesis, that cadherins and integrins function
      redundantly to substitute for one another during epithelium formation (Martinez
      Rico et al., 2010; Ojakian et al., 2001; Rudkouskaya et al., 2014; Weber et al.,
      2011). We use C. elegans, which possesses a single E-cadherin (Costa et al.,
      1998; Hardin et al., 2013; Tepass, 1999) and a single beta-integrin (Gettner et
      al., 1995; Lee et al., 2001), and analyze the arcade cells, which generate an
      epithelium late in embryogenesis (Portereiko and Mango, 2001; Portereiko et al.,
      2004), after most maternal factors are depleted. Loss of E-cadherin(HMR-1) in
      combination with beta-integrin(PAT-3) had no impact on the onset or formation of
      the arcade cell epithelium, nor the epidermis or digestive tract. Moreover, beta
      integrin(PAT-3) was not enriched at the basal surface of the arcades, and the
      candidate PAT-3 binding partner beta-laminin(LAM-1) was not detected until after
      arcade cell polarity was established and exhibited no obvious polarity defect
      when mutated. Instead, the polarity protein par-6 (Chen and Zhang, 2013; Watts et
      al., 1996) was required to polarize the arcade cells, and par-6 mutants exhibited
      mislocalized or absent apical and junctional proteins. We conclude that the
      arcade cell epithelium polarizes by a PAR-6-mediated pathway that is independent
      of E-cadherin, beta-integrin and beta-laminin. 

PMID- 25773365
TI  - Hydroxyurea-mediated neuroblast ablation establishes birth dates of secondary
      lineages and addresses neuronal interactions in the developing Drosophila brain.
AB  - The Drosophila brain is comprised of neurons formed by approximately 100
      lineages, each of which is derived from a stereotyped, asymmetrically dividing
      neuroblast. Lineages serve as structural and developmental units of Drosophila
      brain anatomy and reconstruction of lineage projection patterns represents a
      suitable map of Drosophila brain circuitry at the level of neuron populations
      ("macro-circuitry"). Two phases of neuroblast proliferation, the first in the
      embryo and the second during the larval phase (following a period of mitotic
      quiescence), produce primary and secondary lineages, respectively. Using
      temporally controlled pulses of hydroxyurea (HU) to ablate neuroblasts and their
      corresponding secondary lineages during the larval phase, we analyzed the effect
      on development of primary and secondary lineages in the late larval and adult
      brain. Our findings indicate that timing of neuroblast re-activation is highly
      stereotyped, allowing us to establish "birth dates" for all secondary lineages.
      Furthermore, our results demonstrate that, whereas the trajectory and projection
      pattern of primary and secondary lineages is established in a largely independent
      manner, the final branching pattern of secondary neurons is dependent upon the
      presence of appropriate neuronal targets. Taken together, our data provide new
      insights into the degree of neuronal plasticity during Drosophila brain
      development. 

PMID- 25773366
TI  - Evaluation of short-term predictors of glucose concentration in type 1 diabetes
      combining feature ranking with regression models.
AB  - Glucose concentration in type 1 diabetes is a function of biological and
      environmental factors which present high inter-patient variability. The objective
      of this study is to evaluate a number of features, which are extracted from
      medical and lifestyle self-monitoring data, with respect to their ability to
      predict the short-term subcutaneous (s.c.) glucose concentration of an
      individual. Random forests (RF) and RReliefF algorithms are first employed to
      rank the candidate feature set. Then, a forward selection procedure follows to
      build a glucose predictive model, where features are sequentially added to it in
      decreasing order of importance. Predictions are performed using support vector
      regression or Gaussian processes. The proposed method is validated on a dataset
      of 15 type diabetics in real-life conditions. The s.c. glucose profile along with
      time of the day and plasma insulin concentration are systematically highly
      ranked, while the effect of food intake and physical activity varies considerably
      among patients. Moreover, the average prediction error converges in less than d/2
      iterations (d is the number of features). Our results suggest that RF and
      RReliefF can find the most informative features and can be successfully used to
      customize the input of glucose models. 

PMID- 25773367
TI  - Support vector machine and fuzzy C-mean clustering-based comparative evaluation
      of changes in motor cortex electroencephalogram under chronic alcoholism.
AB  - In this study, the magnitude and spatial distribution of frequency spectrum in
      the resting electroencephalogram (EEG) were examined to address the problem of
      detecting alcoholism in the cerebral motor cortex. The EEG signals were recorded
      from chronic alcoholic conditions (n = 20) and the control group (n = 20). Data
      were taken from motor cortex region and divided into five sub-bands (delta,
      theta, alpha, beta-1 and beta-2). Three methodologies were adopted for feature
      extraction: (1) absolute power, (2) relative power and (3) peak power frequency.
      The dimension of the extracted features is reduced by linear discrimination
      analysis and classified by support vector machine (SVM) and fuzzy C-mean
      clustering. The maximum classification accuracy (88 %) with SVM clustering was
      achieved with the EEG spectral features with absolute power frequency on F4
      channel. Among the bands, relatively higher classification accuracy was found
      over theta band and beta-2 band in most of the channels when computed with the
      EEG features of relative power. Electrodes wise CZ, C3 and P4 were having more
      alteration. Considering the good classification accuracy obtained by SVM with
      relative band power features in most of the EEG channels of motor cortex, it can
      be suggested that the noninvasive automated online diagnostic system for the
      chronic alcoholic condition can be developed with the help of EEG signals. 

PMID- 25773368
TI  - Erythrocyte shape classification using integral-geometry-based methods.
AB  - Erythrocyte shape deformations are related to different important illnesses. In
      this paper, we focus on one of the most important: the Sickle cell disease. This
      disease causes the hardening or polymerization of the hemoglobin that contains
      the erythrocytes. The study of this process using digital images of peripheral
      blood smears can offer useful results in the clinical diagnosis of these
      illnesses. In particular, it would be very valuable to find a rapid and
      reproducible automatic classification method to quantify the number of deformed
      cells and so gauge the severity of the illness. In this paper, we show the good
      results obtained in the automatic classification of erythrocytes in normal cells,
      sickle cells, and cells with other deformations, when we use a set of functions
      based on integral-geometry methods, an active contour-based segmentation method,
      and a k-NN classification algorithm. Blood specimens were obtained from patients
      with Sickle cell disease. Seventeen peripheral blood smears were obtained for the
      study, and 45 images of different fields were obtained. A specialist selected the
      cells to use, determining those cells which were normal, elongated, and with
      other deformations present in the images. A process of automatic classification,
      with cross-validation of errors with the proposed descriptors and with other two
      functions used in previous studies, was realized. 

PMID- 25773369
TI  - Isolated heart models: cardiovascular system studies and technological advances.
AB  - Isolated heart model is a relevant tool for cardiovascular system studies. It
      represents a highly reproducible model for studying broad spectrum of
      biochemical, physiological, morphological, and pharmaceutical parameters,
      including analysis of intrinsic heart mechanics, metabolism, and coronary
      vascular response. Results obtained in this model are under no influence of other
      organ systems, plasma concentration of hormones or ions and influence of
      autonomic nervous system. The review describes various isolated heart models, the
      modes of heart perfusion, and advantages and limitations of various experimental
      setups. It reports the improvements of perfusion setup according to Langendorff
      introduced by the authors. 

PMID- 25773370
TI  - Comparison between human awake, meditation and drowsiness EEG activities based on
      directed transfer function and MVDR coherence methods.
AB  - This study examined the electroencephalogram functional connectivity (coherence)
      and effective connectivity (flow of information) of selected brain regions during
      three different attentive states: awake, meditation and drowsiness. For the
      estimation of functional connectivity (coherence), Welch and minimum variance
      distortionless response (MVDR) methods were compared. The MVDR coherence was
      found to be more suitable since it is both data and frequency dependent and
      enables higher spectral resolution, while Welch's periodogram-based approach is
      both data and frequency independent. The directed transfer function (DTF) method
      was applied in order to estimate the effective connectivity or brain's flow of
      information between different regions during each state. DTF enables to identify
      the main brain areas that initiate EEG activity and the spatial distribution of
      these activities with time. Analysis was conducted using the EEG data of 30
      subjects (ten awake, ten drowsy and ten meditating) focusing on six main
      electrodes (F3, F4, C3, C4, P3, P4, O1 and O2). For each subject, EEG data were
      recorded during 5-min baseline and 15 min of a specific condition (awake,
      meditation or drowsiness). Statistical analysis included the Kruskal-Wallis (KW)
      nonparametric analysis of variance followed by post hoc tests with Bonferroni
      alpha correction. The results reveal that both states of drowsiness and
      meditation states lead to a marked difference in the brain's flow of information
      (effective connectivity) as shown by DTF analyses. In specific, a significant
      increase in the flow of information in the delta frequency band was found only in
      the meditation condition and was further found to originate from frontal (F3,
      F4), parietal (P3, P4) and occipital (O1, O2) regions. Altogether, these results
      suggest that a change in attentiveness leads to significant changes in the
      spectral profile of the brain's information flow as well as in its functional
      connectivity and that these changes can be captured using coherence and DTF
      analyses. 

PMID- 25773371
TI  - Evaluation of measurement and stimulation patterns in open electrical impedance
      tomography with scanning electrode.
AB  - The reconstruction quality in electrical impedance tomography is limited by the
      current injection amplitude, the injection and measurement patterns, and the
      measurement accuracy as well as the number and placement of electrodes. This
      paper dedicates to increase the number of independent voltage measurements by
      scanning electrode (SE), and design an optimal measurement and stimulation
      pattern for open electrical impedance tomography (OEIT). Firstly, several
      measurement patterns are, performed in OEIT, aiming to evaluate the right number
      of the measurement points for the imaged target in a certain depth. The results
      indicate that the image quality gets higher with the number of measurement point
      increased to some extent. Thus, it can guide the optimum design for the electrode
      system in OEIT. Secondly, through the numerical calculation and salt water tank
      experiment, in contrast to adjacent current injection pattern, cross-current
      injection pattern achieves better reconstruction with higher imaging quality and
      penetration depth, and is more robust against data noise in deep domain. Lastly,
      the experiments also indicate that the electrode contact area affects the
      reconstruction quality and investigation depth. Therefore, OEIT with SE can
      improve the application in clinic, such as the detection and monitoring of
      vascular, breast, and pulmonary diseases. 

PMID- 25773372
TI  - Equipoise: ethical, scientific, and clinical trial design considerations for
      compatible pair participation in kidney exchange programs.
AB  - Compatible living donor/recipient pair participation (CPP) in kidney exchange
      (KE) transplantation may substantially increase transplant volumes and
      significantly mitigate the O blood group donor shortage in KE. Initial ethical
      analysis did not support CPP for two primary reasons: (1) KE would be
      "unbalanced," and (2) the possibility of undue influence experienced by the
      compatible pair living donor. Recent developments with CPP (modeling studies and
      small clinical experiences), have demonstrated substantial potential for
      increasing KE volumes. This encouraged us to reconsider initial ethical concerns,
      with a focus on the potential for a design of a prospective CPP clinical trial.
      This ethical reconsideration led us to conclude that the concept of unbalanced
      kidney exchanges (manifested primarily by differential benefit between compatible
      and incompatible pairs) is no longer as clear cut as originally conceived. In
      addition, application of two concepts substantially diminishes ethical concerns
      including: (1) "quasi-compatible" pairs, and (2) a priori definition of
      mitigating factors. We conclude that genuine uncertainty exists regarding whether
      kidney exchange is best performed with or without compatible pair participation
      and that a clinical trial is therefore warranted. 

PMID- 25773373
TI  - Regioselective solid-phase synthesis of N-mono-hydroxylated and N-mono-methylated
      acylpolyamine spider toxins using an 2-(ortho-nitrophenyl)ethanal-modified resin.
AB  - A recently introduced new SPS resin, possessing a 2-(ortho-nitrophenyl)ethanal
      linker, was used for the regioselective on-resin synthesis of N-mono-hydroxylated
      and N-mono-methylated polyamine spider toxins of Agelenopsis aperta and
      Larinioides folium. The polyamine backbones of the target compounds were
      efficiently constructed from the center by reductive amination of the aldehyde
      linker, followed by stepwise alkylation and acylation on solid support. Depending
      on the cleavage conditions, employing either oxidation/Cope elimination or
      methylation/Hofmann elimination, regioselectively the respective N-hydroxyl or N
      methyl products were obtained. Employing this methodology, a number of
      acylpolyamine spider toxins were synthesized and identified as venom components
      by UHPLC and ESI-MS/MS. 

PMID- 25773374
TI  - Surgical outcomes of orbital trapdoor fracture in children and adolescents.
AB  - PURPOSE: Orbital trapdoor fractures are uncommon but more frequent in children
      and adolescents. Orbital trapdoor fractures have been discussed in many previous
      reports, early treatment has been advocated but there is controversy over
      treatment policy and surgical outcomes. Our retrospective study analyzed the
      surgical outcomes of orbital trapdoor fracture in children and adolescents to
      investigate the appropriate timing of treatment and the relationship between
      severity of extraocular muscle movement (EOM) limitation before the operation and
      the period of recovery after operation. METHODS: A total of 44 children and
      adolescents with orbital wall fractures were operated on from 2009 to 2013. This
      study included 25 patients who underwent surgery for orbital trapdoor fractures;
      age range 9-18 years (mean age 14.0). We investigated the interval from trauma to
      surgery, the period of full EOM recovery after operation and the correlation
      between these factors, retrospectively. RESULTS: The mean follow-up duration was
      90.2 days. At follow-up, nine out of ten patients who underwent surgery within 24
      h (Group 1) had full EOM recovery, with a mean recovery time of 25.1 days; five
      out of six patients who underwent surgery within 24-72 h (Group 2) had full EOM
      recovery with a mean recovery time of 60.2 days; and seven out of nine patients
      who underwent surgery after 72 h (Group 3) had full EOM recovery with a mean
      recovery time of 67.6 days. There was no statistical difference in the operation
      success rates between the groups. Also, the four patients that not completely
      recovered EOM had a mild EOM limitation below grade -1. CONCLUSION: In our study,
      we found that patients with orbital trapdoor fractures can recover full EOM
      regardless of the interval from trauma to surgery. Therefore, we suggest that
      appropriate surgical technique is important in the treatment of patients with
      orbital trapdoor fractures, in addition to the urgent surgery recommended for
      these fractures in a pediatric population. Furthermore, we expect a good
      prognosis following the treatment of orbital trapdoor fractures if appropriate
      surgical techniques are used, even if a relatively long time has passed after the
      trauma.

PMID- 25773375
TI  - Long-term results of ORIF of condylar head fractures of the mandible: A
      prospective 5-year follow-up study of small-fragment positional-screw
      osteosynthesis (SFPSO).
AB  - BACKGROUND: Optimum treatment of condylar head fractures (CHF) remains subject to
      controversy. There are currently a variety of alternative techniques applied,
      data in literature are often inconsistent and especially systematic long-term
      data on results after treatment by open reduction and internal fixation (ORIF)
      have so far not been available. This study in hand is the first long-term
      prospective study of ORIF after CHF based on osteosynthesis with 1.7 mm small
      fragment positional screws (SFPSO)via a retroauricular transmeatal approach (RA).
      METHODS: The study made use of radiologic, anatomic and objective functional
      parameters (axiography and MRI) to assess vertical height, disk mobility,
      protrusive and translatory movement as well as potential physical complaints.
      Included were surgical long-term sequelae after RA, such as incidence of stenosis
      of the auditory canal, the facial nerve and resulting disturbance of facial skin
      sensitivity. Retroauricular scars were evaluated according to the Vancouver Scar
      Scale. Helkimo and RDC/TMD indices were applied for patient's self-assessment of
      quality of life aspects after ORIF via RA. The sample in the first follow-up
      trial (FFT) in the years 2003-2004 comprised 26 patients (36 CHF). 22 patients
      (31 CHF) were re-evaluated in a second follow-up trial (SFT) between 2006 and
      2008. A reference collective (43 patients, 56 CHF) treated with ORIF from 1993 to
      2000 mainly by mini- or microplates (MMP) served as a surgical control group.
      RESULTS: Five years after ORIF all fractured condyles (FC) continued to show
      stable anatomic restoration of the pre-trauma vertical height. FC treated with
      SFPSO exhibited a significantly superior range of motion (p < 0.05) of disk and
      condyle during mouth opening and protrusion compared to a previous MMP reference
      collective. Also, no difference was found between condylar mobility of FC five
      years after surgery and non-fractured condyles (NFC). SFPSO had thus successfully
      achieved a sustainable, stable physiological restoration of protrusive mobility
      of the articular disk and condyle. Remarkably, these long-term results were even
      slightly better in SFT vs. FFT (p < 0.05). Except for sporadically occurring
      minor complaints, the patients' subjective overall long-term perception of the
      success of the treatment was equally positive to the surgeons' objective
      assessment. CONCLUSIONS: This first long-term prospective follow-up study, based
      on objective assessment tools, demonstrates that in all cases the major goals of
      ORIF in CHF could be fully achieved. These goals are: restoration of vertical
      height viz. prevention of occlusal disorders, physiological function of disk and
      condyle as well as of the lateral pterygoid muscle. Accordingly, ORIF of CHF e.g.
      with SFPSO and via the RA secures both a long-term functionally and anatomically
      stable result and as best as possible pain-free result for the patient, a central
      prerequisite of optimum perceived HRQoL. The paper has been amended by an
      extensive review part that covers the current knowledge of the major surgical
      aspects regarding the treatment of condylar head fractures.

PMID- 25773376
TI  - Multilevel modeling analysis of dyadic network data with an application to
      Ye'kwana food sharing.
AB  - Behavioral ecologists have recently begun using multilevel modeling for the
      analysis of social behavior. We present a multilevel modeling formulation of the
      Social Relations Model that is well suited for the analysis of dyadic network
      data. This model, which we adapt for count data and small datasets, can be fitted
      using standard multilevel modeling software packages. We illustrate this model
      with an analysis of meal sharing among Ye'kwana horticulturalists in Venezuela.
      In this setting, meal sharing among households is predicted by an association
      index, which reflects the amount of time that members of the households are
      interacting. This result replicates recent findings that interhousehold food
      sharing is especially prevalent among households that interact and cooperate in
      multiple ways. We discuss opportunities for human behavioral ecologists to expand
      their focus to the multiple currencies and cooperative behaviors that
      characterize interpersonal relationships in preindustrial societies. We discuss
      possible extensions to this statistical modeling approach and applications to
      research by human behavioral ecologists and primatologists.

PMID- 25773377
TI  - Proposal of a new method for the use of the Rydel-Seiffer tuning fork in the
      screening of diabetic polyneuropathy. A pilot study.
AB  - We investigated the usefulness of a new examiner-independent method based on the
      duration of vibration sensation following the placement of the Rydel-Seiffer
      tuning fork over the dorsum of the interphalangeal hallux joint. This method
      demonstrated the same diagnostic efficacy as the Rydel-Seiffer method coupled
      with greater ease of use. 

PMID- 25773379
TI  - Methanogenesis produces strong 13C enrichment in stromatolites of Lagoa Salgada,
      Brazil: a modern analogue for Palaeo-/Neoproterozoic stromatolites?
AB  - Holocene stromatolites characterized by unusually positive inorganic delta(13)
      CPDB values (i.e. up to +160/00) are present in Lagoa Salgada, a seasonally
      brackish to hypersaline lagoon near Rio de Janeiro (Brazil). Such positive values
      cannot be explained by phototrophic fixation of CO2 alone, and they suggest that
      methanogenesis was a dominating process during the growth of the stromatolites.
      Indeed, up to 5 mm methane was measured in the porewater. The archaeal membrane
      lipid archaeol showing delta(13) C values between -15 and 00/00 suggests that
      archaea are present and producing methane in the modern lagoon sediment.
      Moreover, (13) C-depleted hopanoids diplopterol and 3beta-methylated C32
      17beta(H),21beta(H)-hopanoic acid (both -400/00) are preserved in lagoon
      sediments and are most likely derived from aerobic methanotrophic bacteria
      thriving in the methane-enriched water column. Loss of isotopically light methane
      through the water column would explain the residual (13) C-enriched pool of
      dissolved inorganic carbon from where the carbonate constituting the
      stromatolites precipitated. The predominance of methanogenic archaea in the
      lagoon is most likely a result of sulphate limitation, suppressing the activity
      of sulphate-reducing bacteria under brackish conditions in a seasonally humid
      tropical environment. Indeed, sulphate-reduction activity is very low in the
      modern sediments. In absence of an efficient carbonate-inducing metabolic
      process, we propose that stromatolite formation in Lagoa Salgada was abiotically
      induced, while the (13) C-enriched organic and inorganic carbon pools are due to
      methanogenesis. Unusually, (13) C-enriched stromatolitic deposits also appear in
      the geological record of prolonged periods in the Palaeo- and Neoproterozoic.
      Lagoa Salgada represents a possible modern analogue to conditions that may have
      been widespread in the Proterozoic, at times when low sulphate concentrations in
      sea water allowed methanogens to prevail over sulphate-reducing bacteria. 

PMID- 25773380
TI  - A lanthanide salen "square prism" and a wrapped exo-lanthanide salen "double
      decker".
AB  - An erbium(iii) salen "square prism" and a supramolecular aggregate of exo
      erbium(iii) salen "double-decker" cations wrapped by an anionic cuprous cyanide
      network were prepared from N,N'-ethylene bis[4-(diethylamino)salicylideneimine.
      Both erbium(iii) edifices show fine-structure near-infrared (NIR) luminescence
      under the excitation in the visible light area. Here we provide a novel and
      efficient method for stabilizing non-isolable lanthanide edifices in the solid
      state. 

PMID- 25773382
TI  - Adding a structured education intervention to a program of exercise training may
      not benefit people with chronic obstructive pulmonary disease.

PMID- 25773383
TI  - Advanced structural analysis of nanoporous materials by thermal response
      measurements.
AB  - Thermal response measurements based on optical adsorption calorimetry are
      presented as a versatile tool for the time-saving and profound characterization
      of the pore structure of porous carbon-based materials. This technique measures
      the time-resolved temperature change of an adsorbent during adsorption of a test
      gas. Six carbide and carbon materials with well-defined nanopore architecture
      including micro- and/or mesopores are characterized by thermal response
      measurements based on n-butane and carbon dioxide as the test gases. With this
      tool, the pore systems of the model materials can be clearly distinguished and
      accurately analyzed. The obtained calorimetric data are correlated with the
      adsorption/desorption isotherms of the materials. The pore structures can be
      estimated from a single experiment due to different adsorption
      enthalpies/temperature increases in micro- and mesopores. Adsorption/desorption
      cycling of n-butane at 298 K/1 bar with increasing desorption time allows to
      determine the pore structure of the materials in more detail due to different
      equilibration times. Adsorption of the organic test gas at selected relative
      pressures reveals specific contributions of particular pore systems to the
      increase of the temperature of the samples and different adsorption mechanisms.
      The use of carbon dioxide as the test gas at 298 K/1 bar provides detailed
      insights into the ultramicropore structure of the materials because under these
      conditions the adsorption of this test gas is very sensitive to the presence of
      pores smaller than 0.7 nm. 

PMID- 25773384
TI  - Prevalence, awareness and treatment of chronic kidney disease among middle-aged
      and elderly: The China Health and Retirement Longitudinal Study.
AB  - AIM: To provide reliable estimates of the prevalence, awareness, and treatment of
      chronic kidney disease (CKD), and their distribution and related influencing
      factors in middle-aged and elderly population in China. METHODS: A cross
      sessional survey called the China Health and Retirement Longitudinal Study
      (CHARLS) was conducted in 2011-2012 in Chinese people aged 45 years or older.
      This was to evaluate the prevalence of CKD, disease awareness compared to other
      chronic diseases in the population, and whether they were being treated for their
      CKD. Estimated GFR (eGFR) was calculated using the Chronic Kidney Disease
      Epidemiology Collaboration eGFR creatinine-cystatin C (eGFRcreat-cys) equation.
      CKD was defined as eGFR less than 60 mL/min per 1.73 m(2) . Multivariable
      logistic regressions were used to estimate odds ratios (ORs) for the risk
      factors. RESULTS: The overall prevalence of CKD was 11.5% (95%CI: 10.1% ~ 12.8%).
      It was higher in urban than rural population (13.0% vs 10.0%, P < 0.05). Among
      all patients with CKD, only 8.7% were aware of the diagnosis. 4.9% of the
      patients were receiving treatment. The proportion of those aware of their
      condition and those who were treated decreased with age in both sexes. Of those
      aware (8.9%), 55.9% were treated. 31.4% of the treated patients took Chinese
      traditional medicine. CONCLUSIONS: There is a surprising prevalence of CKD in the
      Chinese middle-aged and elderly population, with disproportionately low awareness
      and treatment. A comprehensive strategy toward prevention, screening, treatment
      and control of CKD is needed to slow the epidemic of CKD.

PMID- 25773385
TI  - Predictive value of microtubule-associated protein Tau in patients with recurrent
      and metastatic breast cancer treated with taxane-containing palliative
      chemotherapy.
AB  - Tau is a member of microtubule-associated proteins (MAPs) and expressed in normal
      breast epithelium and breast cancer cells. Tau expression levels in early breast
      cancer were correlated with the responsiveness of taxane-containing chemotherapy.
      However, it is unknown whether Tau contributes to breast cancer progression.
      Herein, Tau expression in recurrent and metastatic breast cancer (RMBC) and its
      predictive significance in taxane-containing palliative chemotherapy were
      investigated. Immunohistochemical (IHC) staining was conducted to detect Tau
      protein expression levels in biopsies from 285 patients with RMBC, and the
      correlation between Tau expression and sensitivity to taxane was evaluated. One
      hundred twenty-one (42.46 %, 121/285) patients were Tau positive in their tumor.
      One hundred ninety-four (68.07 %, 194/285) patients were effective clinical
      remission, which evaluated with response evaluation criteria in solid tumors
      (RECIST) criteria. In this group, 141 (85.98 %, 141/194) patients were Tau
      negative. We further analyzed the correlation between Tau expression and
      clinicopathological characteristics. Tau expression was positively correlated to
      estrogen receptor (ER) status. Multivariate logistic regression analysis showed
      that Tau expression significantly differentiated patients with effective response
      to treatment (95 % confidence interval (CI): 4.230-13.88, P < 0.01). Tau
      expression was identified as an independent factor to predict the sensitivity of
      tumors to taxane-containing palliative chemotherapy in RMBC, suggesting that Tau
      expression in RMBC may serve as a clinical predictor for taxane-containing
      palliative chemotherapy.

PMID- 25773386
TI  - Downregulation of Id2 increases chemosensitivity of glioma.
AB  - With its growth characteristic and chemoresistance, glioblastoma is the most
      deadly brain tumor. Twenty-five core genes that influence the chemosensitivity of
      glioblastoma were screened in our previous experiments, and Id2, the inhibitor of
      DNA binding 2, an oncogene encoding a helix-loop-helix protein, was identified.
      The elevated expression levels of Id2 have been reported in several malignancies.
      The aim of this study is to investigate the effects of Id2 expression on the
      chemosensitivity of glioma cells. In this study, Id2 expression was investigated
      in a malignant glioma cell line. Then, we silenced the expression of Id2 with the
      highly specific posttranscriptional suppression of RNA interference (RNAi) in U87
      cells. The changes in response to antitumor agents Me-CCNU, VM26, and TMZ were
      evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT)
      assay. Apoptosis was measured using an annexin V-fluorescein isothiocyanate
      (FITC) apoptosis detection kit. The relationship between Id2 expression and
      caspase 3 was tested by RT-PCR and Western blot. This study demonstrated that Id2
      was significantly upregulated in glioma tissues, and Id2 correlated well with the
      advancement of glioma grade and a worse prognosis in response to temozolomide
      treatment. The RNAi-mediated decrease of Id2 expression enhanced chemosensitivity
      to Me-CCNU, VM26, and TMZ in the U87 cell line. We further discovered that
      silencing of Id2 expression could promote apoptosis of glioblastoma cells, which
      could be attributed to the fact that Id2 affects tumor cell chemosensitivity.
      Downregulation of the Id2 gene by RNAi could increase the chemosensitivity of
      glioblastoma cells. Id2 could be a good molecular target for glioblastoma gene
      therapy.

PMID- 25773387
TI  - The comparison of outcomes between hypofractionated and conventional 3D-CRT
      regimens used in combination with TACE as first-line treatment of advanced
      hepatocellular carcinoma.
AB  - Treatment of primary hepatocellular carcinoma (HCC) with transcatheter hepatic
      arterial chemoembolization (TACE) and three-dimensional conformal radiotherapy
      (3D-CRT) achieves good short-term but poor long-term survival. We retrospectively
      assessed whether outcomes differ between hypofractionated and conventional 3D-CRT
      regimens. Patients were treated in our institution between June 2005 and October
      2009. All patients received two cycles of TACE followed by either
      hypofractionated 3D-CRT (6-8 Gy fractions for 3-4 weeks to 48-64 Gy) or
      conventional 3D-CRT (2 Gy fractions for 6-7 weeks to 60-70 Gy) 4 weeks later. We
      assessed data from 110 patients (55 in each 3D-CRT group). Overall response rates
      were similar in the two groups. Acute adverse event rates were not significantly
      higher in the hypofractionated 3D-CRT group than in the conventional 3D-CRT
      group; two patients and one patient, respectively, died of late radiation-induced
      liver failure. Overall survival at 1 year was 83.6 % in the hypofractionated 3D
      CRT group versus 68.8 % in the conventional 3D-CRT group (P = 0.019), and at 3
      years, it was 31.7 versus 13.9 % (P = 0.004). Median survival was 27.97 versus
      16.13 months (P = 0.002). Hypofractionated 3D-CRT seemed to provide better
      overall survival than conventional 3D-CRT regimens combined with TACE as a first
      line treatment for advanced HCC.

PMID- 25773378
TI  - Efficacy and safety of alirocumab in reducing lipids and cardiovascular events.
AB  - BACKGROUND: Alirocumab, a monoclonal antibody that inhibits proprotein convertase
      subtilisin-kexin type 9 (PCSK9), has been shown to reduce low-density lipoprotein
      (LDL) cholesterol levels in patients who are receiving statin therapy. Larger and
      longer-term studies are needed to establish safety and efficacy. METHODS: We
      conducted a randomized trial involving 2341 patients at high risk for
      cardiovascular events who had LDL cholesterol levels of 70 mg per deciliter (1.8
      mmol per liter) or more and were receiving treatment with statins at the maximum
      tolerated dose (the highest dose associated with an acceptable side-effect
      profile), with or without other lipid-lowering therapy. Patients were randomly
      assigned in a 2:1 ratio to receive alirocumab (150 mg) or placebo as a 1-ml
      subcutaneous injection every 2 weeks for 78 weeks. The primary efficacy end point
      was the percentage change in calculated LDL cholesterol level from baseline to
      week 24. RESULTS: At week 24, the difference between the alirocumab and placebo
      groups in the mean percentage change from baseline in calculated LDL cholesterol
      level was -62 percentage points (P<0.001); the treatment effect remained
      consistent over a period of 78 weeks. The alirocumab group, as compared with the
      placebo group, had higher rates of injection-site reactions (5.9% vs. 4.2%),
      myalgia (5.4% vs. 2.9%), neurocognitive events (1.2% vs. 0.5%), and
      ophthalmologic events (2.9% vs. 1.9%). In a post hoc analysis, the rate of major
      adverse cardiovascular events (death from coronary heart disease, nonfatal
      myocardial infarction, fatal or nonfatal ischemic stroke, or unstable angina
      requiring hospitalization) was lower with alirocumab than with placebo (1.7% vs.
      3.3%; hazard ratio, 0.52; 95% confidence interval, 0.31 to 0.90; nominal P=0.02).
      CONCLUSIONS: Over a period of 78 weeks, alirocumab, when added to statin therapy
      at the maximum tolerated dose, significantly reduced LDL cholesterol levels. In a
      post hoc analysis, there was evidence of a reduction in the rate of
      cardiovascular events with alirocumab. (Funded by Sanofi and Regeneron
      Pharmaceuticals; ODYSSEY LONG TERM ClinicalTrials.gov number, NCT01507831.).

PMID- 25773388
TI  - Note of clarification of data in the paper entitled no association between XRCC1
      gene Arg194Trp polymorphism and risk of lung cancer: evidence based on an updated
      cumulative meta-analysis.

PMID- 25773389
TI  - Genetic variability of glutathione S-transferases influences treatment outcome of
      breast cancer.
AB  - We investigated the relationship between the clinical outcome and the GSTM1
      null/present, GSTT1 null/present, and GSTP1 IIe105Val polymorphisms in breast
      cancer patients with chemotherapy. A total of 420 consecutive breast cancer
      patients diagnosed between January 2010 and December 2011 were eligible for
      inclusion in our retrospective study. The designs of the assay and SNP genotyping
      of GSTM1 null/present, GSTT1 null/present, and GSTP1 IIe105Val were performed
      using the Sequenom MassARRAY platform. In the univariate analysis, patients who
      carried TT genotype and CT + TT genotype of GSTP1 IIe105Val showed a significant
      poorer tumor response to chemotherapy when compared with CC genotype (for TT
      genotype, adjusted OR = 0.44, 95 % CI = 0.22-0.89; for CT + TT genotype, adjusted
      OR = 0.59, 95 % CI = 0.39-0.92). By Cox multivariate analysis, TT genotype and CT
      + TT genotype were associated with increased risk of death from breast cancer,
      and the relationship was more obvious after being adjusted by potential
      confounding factors (for TT genotype, adjusted OR = 4.23, 95 % CI = 2.33-8.76;
      for CT + TT genotype, adjusted OR = 2.53, 95% CI = 1.60-4.03). Polymorphism of
      GSTP1 IIe105Val might affect the clinical outcome in breast cancer patients.

PMID- 25773391
TI  - MicroRNA-191 promotes osteosarcoma cells proliferation by targeting checkpoint
      kinase 2.
AB  - MicroRNAs (miRNAs) are small noncoding RNAs of 19-25 nt that can regulate gene
      expression at a posttranscriptional level. Increasing evidence indicates that
      miRNAs participate in almost every step of cellular processes and are often
      aberrantly expressed in human cancer. The aim of this study was to investigate
      the functional significance of miR-191 and to identify its possible target genes
      in osteosarcoma cells. Here, we found that the expression level of miR-191 was
      increased in osteosarcoma tissues in comparison with the adjacent normal tissues.
      The enforced expression of miR-191 was able to promote cell proliferation in Saos
      2 and MG62 cells, while miR-191 antisense oligonucleotides blocked cell
      proliferation. At the molecular level, our results further revealed that
      expression of tumor suppressor gene, checkpoint kinase 2, was negatively
      regulated by miR-191. Therefore, we consider that miR-191 act as an onco-MicroRNA
      for osteosarcoma and it would offer a new way in molecular targeting cancer
      treatment.

PMID- 25773390
TI  - Correlation of Musashi-1, Lgr5, and pEGFR expressions in human small intestinal
      adenocarcinomas.
AB  - Recent studies have revealed that Musashi-1 and Lgr5 (leucine-rich-repeat
      containing G-protein-coupled receptor 5) were putative stem cell genes. The
      epidermal growth factor receptor (EGFR) has also been extensively studied; it was
      known as an oncogenic driver in cancers. Overexpressions of Musashi-1, EGFR, and
      Lgr5 have been reported in some tumor tissues and cell lines. In this study, we
      used immunohistochemical analysis to investigate the expression pattern of
      Musashi-1, Lgr5, and pEGFR in 38 small intestinal adenocarcinomas (SIAs)
      resection specimens, 20 matched normal specimens and tried to analyze the
      correlations among them. The positive rate of Musashi-1, Lgr5, and pEGFR in SIAs,
      respectively, was 71 % (27/38), 55 % (21/38), and 45 % (17/38). Compared with the
      adjacent normal small intestinal mucosa, Musashi-1, Lgr5, and pEGFR protein were
      overexpressed in SIAs (P< 0.05). Furthermore, Musashi-1 and Lgr5 expressions were
      significantly correlated with the depth of wall invasion (P = 0.0011, P = 0.0017,
      respectively). Musashi-1 expression was closely correlated with Lgr5 (P = 0.015,
      r = 0.392). However, pEGFR expression was not associated with age, gender, tumor
      size, differentiation, depth of invasion, lymphatic metastasis, TNM stage, and
      pEGFR expression was not correlated with Musashi-1 or Lgr5 (P > 0.05, r = 0.064;
      P > 0.05, r = 0.307, respectively). Thus, we suggest that Musashi-1, Lgr5, and
      pEGFR are overexpressed in human SIAs and may play roles in human SIA
      carcinogenesis and progression.

PMID- 25773392
TI  - The role of tumor suppressor gene SOX11 in prostate cancer.
AB  - SOX genes play an important role in a number of developmental processes. The
      transcription factor SOX11 is one of the members of the SOX family emerging as
      important transcriptional regulators. The aim of this study was to investigate
      the role of SOX11 in prostate cancer (PCa) and its expression pattern and
      clinical significance. The gene expression of SOX11 in human PCa tissues compared
      with benign prostate hyperplasia (BPH) tissues was detected using real-time
      quantitative reverse transcriptase-polymerase chain reaction (QRT-PCR) analysis
      and immunohositochemistry. SOX11 overexpression cell model was used to examine
      the role of SOX11 in cell growth and metastasis in vitro. The results showed that
      the positive rate of SOX11 staining was 16.67 % (10/60) in cases of prostatic
      carcinoma and 81.67 % (49/60) in cases of BPH, and the difference of SOX11
      expression between PCa and BPH was statistically significant (P < 0.001). SOX11
      mRNA level was lowly expressed in PCa cell lines compared to RWPE-1. SOX11
      overexpression suppresses PCa cell migration and invasion. In conclusion, our
      findings demonstrate that SOX11 could suppress cell proliferation, migration, and
      invasion of PCa in vitro.

PMID- 25773393
TI  - Correlation of microRNA-10b upregulation and poor prognosis in human gliomas.
AB  - The aim of this study was to detect the association between the microRNA-10b (miR
      10b) expression level and prognosis in glioma patients. Quantitative real-time
      polymerase chain reaction (qRT-PCR) analysis was used to measure the expression
      of miR-10b levels in different-grade glioma tissues and normal brain tissues. The
      relationship between miR-10b expression levels and clinical pathological
      characteristics was statistically analyzed. The influence of miR-10b on survival
      of glioma patients was also analyzed. As a result, miR-10b expression levels in
      glioma tissues were significantly increased compared to those of normal brain
      tissues (p < 0.001). And the increased expression levels were associated with the
      advanced glioma grade (p < 0.001) and larger tumor size (p < 0.001). Moreover,
      the results of the Kaplan-Meier survival curve indicated that overall survival
      (OS) and progression-free survival (PFS) were significantly poorer in the high
      expression-level group than those in the low-expression-level group (p < 0.001).
      Finally, the results of the multivariate Cox regression model indicated that the
      miR-10b expression level was an independent prognostic factor for glioma
      patients. Taken together, these findings offer convincing evidence that increased
      miR-10b expression may be an independent marker to predict poor prognosis in
      patients with gliomas.

PMID- 25773395
TI  - Reaction mechanism of the anomalous formal nucleophilic borylation of organic
      halides with silylborane: combined theoretical and experimental studies.
AB  - Theoretical and experimental studies have been conducted to elucidate the
      mechanism of the formal nucleophilic boryl substitution of aryl and alkyl
      bromides with silylborane in the presence of potassium methoxide. Density
      functional theory was used in conjunction with the artificial force induced
      reaction method in the current study to determine the mechanism of this reaction.
      The results of this analysis led to the identification of a unique carbanion
      mediated mechanism involving the halogenophilic attack of a silyl nucleophile on
      the bromine atom of the substrate. These calculations have, therefore, provided a
      mechanistic rationale for this counterintuitive borylation reaction. Furthermore,
      the good functional group compatibility and high reactivity exhibited by this
      reaction toward sterically hindered substrates can be understood in terms of the
      low activation energy required for the reaction of the silyl nucleophile with the
      bromine atom of the substrate and the subsequent rapid and selective consumption
      of the carbanion species by the in situ generated boron electrophile. The results
      of an experimental study involving the capture of the anion intermediate provided
      further evidence in support of the generation of a carbanion species during the
      course of this reaction. The anomalous formal nucleophilic borylation mechanism
      reported in this study could be used to provide new insights into silicon and
      boron chemistry. 

PMID- 25773394
TI  - NFKB1/NFKBIa polymorphisms are associated with the progression of cervical
      carcinoma in HPV-infected postmenopausal women from rural area.
AB  - Human papillomavirus (HPV) is considered as the major etiological agent for
      development of cervical cancer but alone is not sufficient enough. So, other
      environmental factors and host genetic background may play an important role in
      the development of cervical cancer. HPV carries a minimal amount of structural
      and regulatory proteins so it is apparently dependent on its host for survival.
      NF-kappaB/IkB system plays an important regulatory role in the apoptotic pathway.
      In the present study, a total of 575 consecutive subjects including 285 cases (45
      cervical pre-cancerous and 240 invasive cervical carcinoma) and 290 age- and
      ethnicity-matched controls recruited from Lok Nayak Jai Prakash Hospital and
      Safdarjung Hospital, New Delhi between July 2009 to July 2013 were genotyped for
      NFKB1 -94 insertion/deletion (rs28362491) and NFKBIa 3'-UTR2758A > G (rs696)
      polymorphism by PCR-RFLP followed by sequencing. We observed a positive
      association of NFKB1 -94 insertion/insertion (II) and NFKBIa 3'-UTR 2758 GG
      genotypes with the progression of cervical carcinoma. Cervical cancer patients
      were found more pronounce to be a carrier of II + GG genotype of both the SNPs.
      We also noticed that HPV-infected postmenopausal women having higher parity along
      with the history of tobacco consumption and who carries insertion allele of NFKB1
      -94 polymorphism in association of GG genotype of NFKBIa 3'-UTR polymorphism,
      were more susceptible to develop cervical carcinoma. II + GG genotype together
      were found to have direct proportionality with the aggressiveness of cervical
      carcinoma. In conclusion, alteration in the gene map of NFKB1/NFKBIa helps in the
      progression of cervical cancer accompanied by HPV infection in postmenopausal
      women from rural residential setup who had higher parity along with history of
      tobacco consumption.

PMID- 25773396
TI  - Editorial: The shape of the nosology to come in developmental psychopathology.
AB  - The field has embarked on an effort to better integrate neurobiological and
      psychological dimensions of functioning with putative psychopathological
      syndromes. If successful, this effort aims to be a turning point as impactful as
      the change, a century ago, away from the study of symptom dimensions and toward
      the study of psychopathological syndromes. New statistical and neurobiological
      methods and findings hold considerable promise in this regard, and several papers
      in the present issue underscore these ongoing and important new directions. For
      this proposed direction to succeed, however, three guiding principles are
      necessary. First, the syndromal approach must continue to be viewed as
      provisional, and not reified. Second, in contrast, individual dimensions of
      neurobiology, psychology, personality, or symptoms should not be decontextualized
      but considered in relation to other traits and dimensions, syndromal
      configurations. Major clinical syndromes cannot be ignored. Third, following the
      Kraepelian insights of a century ago in addition to the more recent insights of
      developmental psychopathlogy, trait and dimension aspects of psychopathology need
      to be understood in their developmental context. Whether an integrated
      dimensional-categorical-developmental understanding of psychopathology can be
      extended to the entire nosology or only parts of it remains to be seen. 

PMID- 25773397
TI  - Draft guidelines regarding appropriate use of (131)I-MIBG radiotherapy for
      neuroendocrine tumors : Guideline Drafting Committee for Radiotherapy with (131)I
      MIBG, Committee for Nuclear Oncology and Immunology, The Japanese Society of
      Nuclear Medicine.
AB  - Since the 1980s when clinical therapeutic trials were initiated, (131)I-MIBG
      radiotherapy has been used in foreign countries for unresectable neuroendocrine
      tumors including malignant pheochromocytomas and neuroblastomas. In Japan, (131)I
      MIBG radiotherapy has not been approved by the Ministry of Health, Labour and
      Welfare; however, personally imported (131)I-MIBG is now available for
      therapeutic purposes in a limited number of institutions. These updated draft
      guidelines aim to provide useful information concerning (131)I-MIBG radiotherapy,
      to help prevent side effects and protect physicians, nurses, other health care
      professionals, patients and their families from radiation exposure. The committee
      has also provided appendices on topics such as practical guidance for attending
      physicians, patient management, and referring physicians. 

PMID- 25773398
TI  - Spatial heterogeneity in landscape structure influences dispersal and genetic
      structure: empirical evidence from a grasshopper in an agricultural landscape.
AB  - Dispersal may be strongly influenced by landscape and habitat characteristics
      that could either enhance or restrict movements of organisms. Therefore, spatial
      heterogeneity in landscape structure could influence gene flow and the spatial
      structure of populations. In the past decades, agricultural intensification has
      led to the reduction in grassland surfaces, their fragmentation and
      intensification. As these changes are not homogeneously distributed in
      landscapes, they have resulted in spatial heterogeneity with generally less
      intensified hedged farmland areas remaining alongside streams and rivers. In this
      study, we assessed spatial pattern of abundance and population genetic structure
      of a flightless grasshopper species, Pezotettix giornae, based on the surveys of
      363 grasslands in a 430-km2 agricultural landscape of western France. Data were
      analysed using geostatistics and landscape genetics based on microsatellites
      markers and computer simulations. Results suggested that small-scale intense
      dispersal allows this species to survive in intensive agricultural landscapes. A
      complex spatial genetic structure related to landscape and habitat
      characteristics was also detected. Two P. giornae genetic clusters bisected by a
      linear hedged farmland were inferred from clustering analyses. This linear hedged
      farmland was characterized by high hedgerow and grassland density as well as
      higher grassland temporal stability that were suspected to slow down dispersal.
      Computer simulations demonstrated that a linear-shaped landscape feature limiting
      dispersal could be detected as a barrier to gene flow and generate the observed
      genetic pattern. This study illustrates the relevance of using computer
      simulations to test hypotheses in landscape genetics studies. 

PMID- 25773399
TI  - The distribution pattern of HMB-45-positive cells is helpful for the diagnosis of
      early acral lentiginous melanoma in situ.

PMID- 25773400
TI  - Platelet and endothelial cell P-selectin are required for host defense against
      Klebsiella pneumoniae-induced pneumosepsis.
AB  - BACKGROUND: Sepsis is associated with activation of platelets and endothelial
      cells accompanied by enhanced P-selectin surface expression. Both platelet- and
      endothelial P-selectin have been associated with leukocyte recruitment and
      induction of inflammatory alterations. Klebsiella (K.) pneumoniae is a common
      human sepsis pathogen, particularly in the context of pneumonia. METHODS: Wild
      type (WT) and P-selectin-deficient (Selp(-/-) ) mice or bone marrow chimeric mice
      were infected with K. pneumoniae via the airways to induce pneumosepsis. Mice
      were sacrificed during early (12 h after infection) or late-stage (44 h) sepsis
      for analyses, or followed in a survival study. RESULTS: Selp(-/-) mice displayed
      10-1000-fold higher bacterial burdens in the lungs, blood and distant organs
      during late-stage sepsis. P-selectin deficiency did not influence leukocyte
      recruitment to the lungs, but was associated with decreased platelet-monocyte
      complexes and increased cytokine release. Bone marrow transfer studies revealed a
      role for both platelet and endothelial cell P-selectin as mice deficient in
      platelet or endothelial cell P-selectin displayed an intermediate phenotype in
      bacterial loads and survival compared with full wild-type or full knockout
      control mice. CONCLUSION: Both platelet and endothelial cell P-selectin
      contribute to host defense during Klebsiella pneumosepsis.

PMID- 25773401
TI  - Plasmon-assisted audio recording.
AB  - We present the first demonstration of the recording of optically encoded audio
      onto a plasmonic nanostructure. Analogous to the "optical sound" approach used in
      the early twentieth century to store sound on photographic film, we show that
      arrays of gold, pillar-supported bowtie nanoantennas could be used in a similar
      fashion to store sound information that is transferred via an amplitude modulated
      optical signal to the near field of an optical microscope. Retrieval of the audio
      information is achieved using standard imaging optics. We demonstrate that the
      sound information can be stored either as time-varying waveforms or in the
      frequency domain as the corresponding amplitude and phase spectra. A "plasmonic
      musical keyboard" comprising of 8 basic musical notes is constructed and used to
      play a short song. For comparison, we employ the correlation coefficient, which
      reveals that original and retrieved sound files are similar with maximum and
      minimum values of 0.995 and 0.342, respectively. We also show that the pBNAs
      could be used for basic signal processing by ablating unwanted frequency
      components on the nanostructure thereby enabling physical notch filtering of
      these components. Our work introduces a new application domain for plasmonic
      nanoantennas and experimentally verifies their potential for information
      processing. 

PMID- 25773402
TI  - Medications for type 2 diabetes: how will we be treating patients in 50 years?
AB  - The past 50 years have seen the development of many new options for treating and
      preventing type 2 diabetes. Despite this success, the individual and societal
      burden of the disease continues unabated. Thus, the next 50 years will be
      critical if we are going to quell the major non-communicable disease of our time.
      The knowledge we will gain in the next few years from clinical studies will
      inform treatment guidelines with regard to which agents to use in whom and
      whether more aggressive approaches can slow the development of hyperglycaemia in
      those at high risk. Beyond that, we anticipate identification of novel targets
      and techniques for therapeutic intervention. These advances will lead to more
      personalised approaches to treatment. Most importantly, we will need to focus our
      political and economic efforts on enhancing and implementing public health
      approaches aimed at prevention of diabetes and its co-morbidities. 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- 25773403
TI  - Blood pressure level and risk of major cardiovascular events and all-cause of
      mortality in patients with type 2 diabetes and renal impairment: an observational
      study from the Swedish National Diabetes Register.
AB  - AIMS/HYPOTHESIS: We assessed the relationship between BP and risk of
      cardiovascular events (CVEs) and all-cause mortality in patients with type 2
      diabetes and renal impairment (estimated GFR < 60 ml min(-1) 1.73 m(-2)) treated
      in clinical practice. METHODS: A total of 33,356 patients (aged 75 +/- 9 years,
      diabetes duration of 10 +/- 8 years) with at least one serum creatinine and BP
      value available in the Swedish National Diabetes Register between 2005 and 2007
      were followed up until 2011 or death. The relationships between mean BPs, CVEs
      and all-cause mortality were examined using time-dependent Cox models to estimate
      HRs, adjusting for cardiovascular risk factors and ongoing medications. RESULTS:
      During the follow-up period (mean 5.3 years), 11,317 CVEs and 10,738 deaths
      occurred. The lowest risks of CVEs and all-cause mortality were observed with a
      systolic BP (SBP) of 135-139 and a diastolic BP (DBP) of 72-74 mmHg, and the
      highest risks were observed for those with SBP intervals 80-120 (CVE HR 2.3 [95%
      CI 2.0, 2.6] and all-cause mortality HR 2.4, [95% CI 2.1, 2.7]) and 160-230 mmHg
      (CVE HR 3.0 [95% CI 2.6, 3.3] and all-cause mortality HR 2.0 [95% CI 1.8-2.3])
      and DBP intervals 40-63 mmHg (CVE HR 2.0 [95% CI 1.8, 2.2], all-cause mortality
      HR 2.0 [95% CI 1.8, 2.2]) and 83-125 mmHg (CVE HR 2.3 [95% CI 2.0, 2.5], all
      cause mortality HR 2.3 [95% CI 2.0, 2.6]). CONCLUSIONS/INTERPRETATION: In this
      nationwide cohort of patients with type 2 diabetes and renal impairment, the risk
      of CVEs and all-cause mortality increased significantly with both high and low
      BPs, while an SBP of 135-139 mmHg and DBP of 72-74 mmHg were associated with the
      lowest risks of CVEs and death.

PMID- 25773404
TI  - A live-cell, high-content imaging survey of 206 endogenous factors across five
      stress conditions reveals context-dependent survival effects in mouse primary
      beta cells.
AB  - AIMS/HYPOTHESIS: Beta cell death is a hallmark of diabetes. It is not known
      whether specific cellular stresses associated with type 1 or type 2 diabetes
      require specific factors to protect pancreatic beta cells. No systematic
      comparison of endogenous soluble factors in the context of multiple pro-apoptotic
      conditions has been published. METHODS: Primary mouse islet cells were cultured
      in conditions mimicking five type 1 or type 2 diabetes-related stresses: basal 5
      mmol/l glucose, cytokine cocktail (25 ng/ml TNF-alpha, 10 ng/ml IL-1beta, 10
      ng/ml IFN-gamma), 1 MUmol/l thapsigargin, 1.5 mmol/l palmitate and 20 mmol/l
      glucose (all in the absence of serum). We surveyed the effects of a library of
      206 endogenous factors (selected based on islet expression of their receptors) on
      islet cell survival through multi-parameter, live-cell imaging. RESULTS: Our
      survey pointed to survival factors exhibiting generalised protective effects
      across conditions meant to model different types of diabetes and stages of the
      diseases. For example, our survey and follow-up experiments suggested that OLFM1
      is a novel protective factor for mouse and human beta cells across multiple
      conditions. Most strikingly, we also found specific protective survival factors
      for each model stress condition. For example, semaphorin4A (SEMA4A) was toxic to
      islet cells in the serum-free baseline and serum-free 20 mmol/l glucose
      conditions, but protective in the context of lipotoxicity. Rank product testing
      supported the consistency of our observations. CONCLUSIONS/INTERPRETATION:
      Collectively, our survey reveals previously unidentified islet cell survival
      factors and suggest their potential utility in individualised medicine.

PMID- 25773406
TI  - Impact of cancer on use of glucose-lowering drug treatment in individuals with
      diabetes: potential mechanisms.

PMID- 25773407
TI  - Teledermatology: from historical perspective to emerging techniques of the modern
      era: part I: History, rationale, and current practice.
AB  - Telemedicine is the use of telecommunications technology to support health care
      at a distance. Technological advances have progressively increased the ability of
      clinicians to care for diverse patient populations in need of skin expertise.
      Dermatology relies on visual cues that are easily captured by imaging
      technologies, making it ideally suited for this care model. Moreover, there is a
      shortage of medical dermatologists in the United States, where skin disorders
      account for 1 in 8 primary care visits and specialists tend to congregate in
      urban areas. Even in regions where dermatologic expertise is readily accessible,
      teledermatology may serve as an alternative that streamlines health care delivery
      by triaging chief complaints and reducing unnecessary in-person visits. In
      addition, many patients in the developing world have no access to dermatologic
      expertise, rendering it possible for teledermatologists to make a significant
      contribution to patient health outcomes. Teledermatology also affords educational
      benefits to primary care providers and dermatologists, and enables patients to
      play a more active role in the health care process by promoting direct
      communication with dermatologists. 

PMID- 25773405
TI  - CGM-measured glucose values have a strong correlation with C-peptide, HbA1c and
      IDAAC, but do poorly in predicting C-peptide levels in the two years following
      onset of diabetes.
AB  - AIMS/HYPOTHESIS: The aim of this work was to assess the association between
      continuous glucose monitoring (CGM) data, HbA1c, insulin-dose-adjusted HbA1c
      (IDAA1c) and C-peptide responses during the first 2 years following diagnosis of
      type 1 diabetes. METHODS: A secondary analysis was conducted of data collected
      from a randomised trial assessing the effect of intensive management initiated
      within 1 week of diagnosis of type 1 diabetes, in which mixed-meal tolerance
      tests were performed at baseline and at eight additional time points through 24
      months. CGM data were collected at each visit. RESULTS: Among 67 study
      participants (mean age [+/- SD] 13.3 +/- 5.7 years), HbA1c was inversely
      correlated with C-peptide at each time point (p < 0.001), as were changes in each
      measure between time points (p < 0.001). However, C-peptide at one visit did not
      predict the change in HbA1c at the next visit and vice versa. Higher C-peptide
      levels correlated with increased proportion of CGM glucose values between 3.9 and
      7.8 mmol/l and lower CV (p = 0.001 and p = 0.02, respectively) but not with CGM
      glucose levels <3.9 mmol/l. Virtually all participants with IDAA1c < 9 retained
      substantial insulin secretion but when evaluated together with CGM, time in the
      range of 3.9-7.8 mmol/l and CV did not provide additional value in predicting C
      peptide levels. CONCLUSIONS/INTERPRETATION: In the first 2 years after diagnosis
      of type 1 diabetes, higher C-peptide levels are associated with increased sensor
      glucose levels in the target range and with lower glucose variability but not
      hypoglycaemia. CGM metrics do not provide added value over the IDAA1c in
      predicting C-peptide levels.

PMID- 25773408
TI  - Teledermatology: from historical perspective to emerging techniques of the modern
      era: part II: Emerging technologies in teledermatology, limitations and future
      directions.
AB  - Telemedicine is the use of telecommunications technology to support health care
      at a distance. Dermatology relies on visual cues that are easily captured by
      imaging technologies, making it ideally suited for this care model. Advances in
      telecommunications technology have made it possible to deliver high-quality skin
      care when patient and provider are separated by both time and space. Most
      recently, mobile devices that connect users through cellular data networks have
      enabled teledermatologists to instantly communicate with primary care providers
      throughout the world. The availability of teledermoscopy provides an additional
      layer of visual information to enhance the quality of teleconsultations.
      Teledermatopathology has become increasingly feasible because of advances in
      digitization of entire microscopic slides and robot-assisted microscopy. Barriers
      to additional expansion of these services include underdeveloped infrastructure
      in remote regions, fragmented electronic medical records, and varying degrees of
      reimbursement. Teleconsultants also confront special legal and ethical challenges
      as they work toward building a global network of practicing physicians. 

PMID- 25773410
TI  - Commentary: Wound edge eversion: surgical dogma or diversion?

PMID- 25773409
TI  - Association of atopic dermatitis with being overweight and obese: a systematic
      review and metaanalysis.
AB  - BACKGROUND: Previous studies found conflicting results about whether atopic
      dermatitis (AD) is associated with overweight/obesity. OBJECTIVE: We sought to
      examine the relationship between AD and overweight/obesity by performing a
      systematic review and metaanalysis. METHODS: Observational studies of the
      relationship between AD and overweight/obesity were selected from PubMed, Embase,
      and the Cochrane Library. The quality of evidence was assessed using the
      Newcastle-Ottawa Scale. Fixed and random effects metaanalyses were performed to
      estimate pooled odds ratios (ORs). Sensitivity analyses were performed that
      compared results by location of study, study quality, and between studies in
      children and adults. RESULTS: In total, 30 studies were included for review.
      Patients who were overweight (Cochrane-Mantel-Haenszel [CMH] OR, 1.27 [95%
      confidence interval {CI}: 1.19-1.36]; random effects OR, 1.23 [95% CI: 1.11
      1.41]), obese (CMH OR, 1.68 [95% CI: 1.54-1.84]; random effects OR, 1.47 [95% CI:
      1.21-1.79]), or overweight/obese (CMH OR, 1.42 [95% CI: 1.34-1.50]; random
      effects OR, 1.31 [95% CI: 1.16-1.48]) had higher odds of AD than normal weight
      patients. In sensitivity analyses, children who were overweight (random effects
      OR, 1.24 [95% CI: 1.08-1.43]), obese (random effects OR, 1.44 [95% CI: 1.12
      1.86]), or overweight/obese (random effects OR, 1.32 [95% CI: 1.15-1.51]) and
      adults who were obese (random effects OR, 1.56 [95% CI: 1.24-1.95]) or
      overweight/obese (random effects OR, 1.29 [95% CI: 1.05-1.59]) had higher odds of
      AD. The association remained significant in North America and Asia but not
      Europe. LIMITATIONS: Most studies were cross-sectional. CONCLUSIONS:
      Overweight/obesity in North America and Asia is associated with an increased
      prevalence of AD.

PMID- 25773411
TI  - Paraphenylenediamine in black henna temporary tattoos: 12-year Food and Drug
      Administration data on incidence, symptoms, and outcomes.

PMID- 25773412
TI  - Attitudes and trends in the treatment of morphea: a national survey.

PMID- 25773413
TI  - New immunologic pathways in the pathogenesis of leprosy: role for Th22 cytokines
      in the polar forms of the disease.

PMID- 25773414
TI  - Awareness and engagement in political advocacy among dermatology residents: a
      needs assessment.

PMID- 25773415
TI  - Patient satisfaction with different treatment modalities for vitiligo.

PMID- 25773416
TI  - Randomized, parallel group trial comparing home-based phototherapy with
      institution-based 308 excimer lamp for the treatment of focal vitiligo vulgaris.

PMID- 25773417
TI  - Successful treatment of refractory Hailey-Hailey disease with a 595-nm pulsed dye
      laser: a series of 7 cases.

PMID- 25773418
TI  - The readability of patient education materials designed for patients with
      psoriasis: what have we learned in 20 years?

PMID- 25773419
TI  - RASopathic alopecia: hair changes associated with vemurafenib therapy.

PMID- 25773420
TI  - Time to update guidelines on screening for latent tuberculosis infection in
      dermatologic patients being treated with tumor necrosis factor-alfa inhibitors.

PMID- 25773421
TI  - Reply to: "Time to update guidelines on screening for latent tuberculosis
      infection in dermatologic patients being treated with tumor necrosis factor-alfa
      inhibitors".

PMID- 25773422
TI  - Reply to: "Time to update guidelines on screening for latent tuberculosis
      infection in dermatologic patients being treated with tumor necrosis factor-alfa
      inhibitors".

PMID- 25773423
TI  - Response to CME article "Screening, early detection, education, and trends for
      melanoma: current status (2007-2013) and future directions. Part I. Epidemiology,
      high-risk groups, clinical strategies, and diagnostic technology".

PMID- 25773424
TI  - Reply to "Surgical margins for melanoma in situ: when 5-mm margins are really 9
      mm".

PMID- 25773425
TI  - Surgical margins for melanoma in situ: when 5-mm margins are really 9 mm.

PMID- 25773426
TI  - Hair dye: a trichoscopy pitfall.

PMID- 25773427
TI  - A practical method to indicate alignment in wound closure with subcuticular
      sutures using the patient's own blood.

PMID- 25773428
TI  - The hypodermic needle as a dermabrading device for recipient area preparation for
      skin grafting in vitiligo.

PMID- 25773433
TI  - Pigmented mammary Paget disease mimicking cutaneous malignant melanoma.

PMID- 25773434
TI  - Pigmented Spitz nevus simulating a solitary angiokeratoma.

PMID- 25773435
TI  - The absolute bioavailability investigation of LS177 in rats using ultra
      performance liquid chromatography-tandem mass spectrometry.
AB  - LS177 is a novel inhibitor of mesenchymal epithelial transition (MET) that was
      used as an anticancer agent. The present study was to evaluate the absolute
      bioavailability of LS177 in rats. A rapid and sensitive ultra-high performance
      liquid chromatography-mass spectrometry (UHPLC-MS/MS) method has been developed
      and validated for the determination of LS177 in rat plasma. LS177 and internal
      standard (IS, LS410) were extracted from rat plasma samples by protein
      precipitation (PPT) for intravenous group and liquid-liquid extraction (LLE)
      procedure for oral group, then separated on a Phenomenex Kinetex XB-C18 (2.1 mm
      I.D. * 50 mm, 2.6 um) using a mobile phase consisting of 0.1% formic acid in
      acetonitrile-0.1% formic acid water with a gradient elution program. The standard
      curves were linear over the ranges of 5.0-2000.0 ng . mL(-1) for PPT and 1.0
      200.0 ng . mL(-1) for LLE. The mean recovery of LS177 was greater than 83.4% for
      PPT and not less than 88.5% for LLE, respectively. The intra- and inter-day
      accuracy and precision were within the acceptable limits of less than 15.0% at
      all concentrations. The validated method was successfully applied to the
      bioavailability study in rat plasma of LS177 and its absolute bioavailability was
      25.37%.

PMID- 25773436
TI  - Ontogenetic taurine biosynthesis ability in rainbow trout (Oncorhynchus mykiss).
AB  - Taurine (2-aminoethane sulfonic acid) plays important roles in multiple
      physiological processes including osmoregulation, bile salt conjugation and
      membrane protection. It is known that taurine biosynthesis varies in different
      fish species. However, its ontogenetic regulation has not been clear. In the
      present study, we found that the hepatic concentrations of taurine increased
      marginally with rainbow trout growth. The mRNA expression, protein levels and
      enzyme activities of key enzymes involved in taurine biosynthesis, cysteine
      dioxygenase (CDO) and cysteine sulfinate decarboxylase (CSD), were analyzed. Our
      results showed that the mRNA levels and protein abundances of CSD increased
      dramatically with the development of rainbow trout stages while the enzyme
      activities showed a slight improvement. However, the expression and activities of
      CDO decreased with rainbow trout growth. These results provide valuable
      information on defining the exact supplementation of taurine in diets for
      different stages of rainbow trout and give new insights into elucidating the
      regulation of taurine metabolism in rainbow trout. 

PMID- 25773437
TI  - Oral symptoms significantly higher among long-term khat (Catha edulis) users in
      Ethiopia.
AB  - OBJECTIVES: Associations between khat (Catha edulis) chewing and different
      adverse oral-dental health conditions have been reported, yet evidence is still
      lacking. This study was designed to investigate the association between long-term
      regular khat chewing and self-reported oral symptoms. METHODS: A cross-sectional
      study was conducted on a sample of 1,255 university students in southern
      Ethiopia. Data on khat chewing status, a range of oral symptoms and other
      pertinent variables were collected using self-administered questionnaires. The
      association between long-term regular khat chewing and oral symptom count was
      investigated using negative binomial regression. RESULTS: The mean oral symptom
      count among long-term regular khat chewers was 1.75 (standard deviation [SD],
      2.18; standard error [SE], 0.31), whereas that among those who were not long-term
      regular khat chewers was 1.18 (SD, 1.68; SE, 0.10). After adjustment for other
      variables, long-term regular khat chewers had approximately 50% more oral
      symptoms than those who were not long-term chewers did (adjusted count ratio,
      1.53; 95% confidence interval, 1.12 to 2.10). CONCLUSIONS: Long-term khat chewing
      negatively affects the oral health of young university students.

PMID- 25773438
TI  - Cost-effectiveness analysis of low density lipoprotein cholesterol-lowering
      therapy in hypertensive patients with type 2 diabetes in Korea: single-pill
      regimen (amlodipine/atorvastatin) versus double-pill regimen
      (amlodipine+atorvastatin).
AB  - OBJECTIVES: Single-pill combination therapy (amlodipine/atorvastatin) might be
      more effective than double-pill therapy (amlodipine+atorvastatin) in patients
      with diabetes and concomitant hypertension requiring statin therapy. We compared
      the cost-effectiveness of a single-pill with that of double-pill for control of
      low density lipoprotein cholesterol (LDL-C) levels, with the ultimate goal of
      cardiovascular disease prevention, in these patients using a cost-effectiveness
      analysis model that considered medication adherence. METHODS: Effectiveness was
      defined as the percentage (%) attainment of target LDL-C levels (<100 mg/dL)
      based on adherence for each therapy. Adherence was defined as compliance to
      medication (>=80% proportion of days covered). A systematic review of the
      literature was conducted to determine the proportion of patients who were
      adherent and target goal attainment based on adherence level. The annual
      medication costs were based on the adherence levels for each regimen. The average
      cost-effectiveness ratio (ACER) was calculated as the cost per % attainment of
      the target LDL-C level. RESULTS: The ACER for the single-pill regimen was lower
      than for the double-pill regimen (4,123 vs. 6,062 Korean won per 1% achievement
      of target goal). Compared with the double-pill, the medication costs were
      approximately 32% lower with the single-pill. CONCLUSION: A single-pill for
      reductions in LDL-C is cost-effective compared with double-pill in hypertensive
      patients with type 2 diabetes.

PMID- 25773439
TI  - Tularemia, a re-emerging infectious disease in Iran and neighboring countrie.
AB  - OBJECTIVES: Tularemia is a zoonotic disease transmitted by direct contact with
      infected animals and through arthropod bites, inhalation of contaminated
      aerosols, ingestion of contaminated meat or water, and skin contact with any
      infected material. It is widespread throughout the northern hemisphere, including
      Iran and its neighbors to the north, northeast, and northwest. METHODS: In this
      paper, the epidemiology of tularemia as a re-emerging infectious disease in the
      world with a focus on Iran and the neighboring countries is reviewed. RESULTS: In
      Iran, positive serological tests were first reported in 1973, in wildlife and
      domestic livestock in the northwestern and southeastern parts of the country. The
      first human case was reported in 1980 in the southwest of Iran, and recent
      studies conducted among at-risk populations in the western, southeastern, and
      southwestern parts of Iran revealed seroprevalences of 14.4, 6.52, and 6%,
      respectively. CONCLUSIONS: Several factors may explain the absence of reported
      tularemia cases in Iran since 1980. Tularemia may be underdiagnosed in Iran
      because Francisella tularensis subspecies holarctica is likely to be the major
      etiological agent and usually causes mild to moderately severe disease.
      Furthermore, tularemia is not a disease extensively studied in the medical
      educational system in Iran, and empirical therapy may be effective in many cases.
      Finally, it should be noted that laboratories capable of diagnosing tularemia
      have only been established in the last few years. Since both recent and older
      studies have consistently found tularemia antibodies in humans and animals, the
      surveillance of this disease should receive more attention. In particular, it
      would be worthwhile for clinical researchers to confirm tularemia cases more
      often by isolating F. tularensis from infected humans and animals.

PMID- 25773440
TI  - An epidemiological comparative study on diagnosis of rodent leptospirosis in
      Mazandaran Province, northern Iran.
AB  - OBJECTIVES: Leptospirosis is a zoonosis caused by leptospires, in which
      transmission occurs through contact with contaminated biological fluids from
      infected animals. Rodents can act as a source of infection for humans and
      animals. The disease has a global distribution, mainly in humid, tropical and sub
      tropical regions. The aim of this study was to compare culture assays, the
      microscopic agglutination test (MAT), polymerase chain reaction (PCR), and nested
      PCR (n-PCR), for the diagnosis of leptospirosis in rodents in Mazandaran
      Province, northern Iran. METHODS: One hundred fifty-one rodents were trapped
      alive at 10 locations, and their urine and kidney samples were collected and used
      for the isolation of live Leptospira. The infecting serovars were identified and
      the antibody titres were measured by MAT, using a panel of 20 strains of live
      Leptospira species as antigens. The presence of leptospiral DNA was evaluated in
      urine and kidney samples using PCR and n-PCR. RESULTS: No live leptospires were
      isolated from the kidney and urine samples of the rodents. Different detection
      rates of leptospirosis were observed with MAT (21.2%), PCR (11.3%), and n-PCR
      (3.3%). The dominant strain was Leptospira serjoehardjo (34.4%, p=0.28), although
      other serotypes were also found. The prevalence of positive leptospirosis tests
      in rodents was 15.9, 2.6, and 2.6% among Rattus norvegicus, R. rattus, and
      Apodemus sylvaticus, respectively. CONCLUSIONS: Leptospirosis was prevalent in
      rodents in Mazandaran Province, northern Iran. MAT was able to detect leptospires
      more frequently than culture or PCR. The kidney was a more suitable site for
      identifying leptospiral DNA by n-PCR than urine. Culture was not found to be an
      appropriate technique for clinical diagnosis.

PMID- 25773441
TI  - Value-based medicine: concepts and application.
AB  - Global healthcare in the 21st century is characterized by evidence-based medicine
      (EBM), patient-centered care, and cost effectiveness. EBM involves clinical
      decisions being made by integrating patient preference with medical treatment
      evidence and physician experiences. The Center for Value-Based Medicine suggested
      value-based medicine (VBM) as the practice of medicine based upon the patient
      perceived value conferred by an intervention. VBM starts with the best evidence
      based data and converts it to patient value-based data, so that it allows
      clinicians to deliver higher quality patient care than EBM alone. The final goals
      of VBM are improving quality of healthcare and using healthcare resources
      efficiently. This paper introduces the concepts and application of VBM and
      suggests some strategies for promoting related research. 

PMID- 25773442
TI  - Epidemiological evidences on overdiagnosis of prostate and kidney cancers in
      Korean.
AB  - OBJECTIVES: The prostate specific antigen test is widely used as the main method
      of screening prostate cancer in Korea. Additionally, the use of ultrasound
      sonography may lead to overdiagnosis of kidney cancer as well as thyroid cancer.
      This study aimed to highlight epidemiological evidences regarding overdiagnosis
      of prostate and kidney cancers in Korean. METHODS: The annual trends of national
      incidence and mortality of prostate and kidney cancers provided by the Korean
      Statistical Information Service were evaluated. RESULTS: The rate of increase in
      the incidence of prostate and kidney cancer was 6 and 5 times higher than that of
      mortality between 2000 and 2011, respectively. Additionally, the age group
      showing the highest incidence in prostate cancer shifted from 85 years and older
      to 75-79 years. CONCLUSIONS: This evidence suggests that prostate and kidney
      cancers are overdiagnosed in Korea. Further research in this area, using national
      cancer registry databases, should be encouraged to prevent overdiagnosis.

PMID- 25773443
TI  - Trends of liver cancer and its major risk factors in Korea.
AB  - The Republic of Korea (hereafter Korea) is one of the countries with high
      incidence of liver cancer and there is great difference in incidence of liver
      cancer between male and female. We investigated the sex-specific trends of three
      major risk factors of liver cancer, which are hepatitis B virus(HBV) infection,
      hepatitis C virus(HCV) infection, and alcoholic liver cirrhosis. The incidence of
      liver cancer was obtained from the Cancer Registration Statistics of the National
      Cancer Center of Korea. Hepatitis B surface antigen (HBsAg) seropositivity was
      based on data from the 2011 Korea National Health and Nutrition Examination
      Survey. Disease statistics from the Health Insurance Review and Assessment
      Service of Korea were used to evaluate trends in HCV infection and alcoholic
      liver cirrhosis. The prevalence of these risk factors were compared with the
      incidence of liver cancer. Males had a three to four times higher incidence of
      liver cancer than females did from 1999 to 2011. This gap between the incidence
      for males and females increased with age and males aged 50 to 59 showed a five
      times higher incidence than females of the same age did. In general, HBsAg
      seropositivity decreased from 1998 to 2011. The prevalence of HCV infections was
      96.2 and 90.3 per 100,000 females and males, respectively in 2013. The
      prevalences of HCV infections from 2009 to 2013 did not substantially differ. The
      annual average prevalence of alcoholic liver cirrhosis from 2009 to 2013 was
      77.22 and 8.90 per 100,000 males and females, respectively; the prevalence among
      males was 8.7 times higher than that among females. The prevalence rapidly
      increased with age in males, and males aged 60 to 69 peaked with a 19.2 times
      higher prevalence than that among females of the same age group. We found that
      the incidence of alcoholic liver cirrhosis, a major risk factor of liver cancer,
      exhibited a trend similar to that of liver cancer incidence in males, and this
      trend also differed remarkably by sex. 

PMID- 25773444
TI  - Lessons from pollution control: response to Heller and Hobbs 2014.

PMID- 25773445
TI  - Long-term efficacy of glycerine-processed amniotic membrane transplantation in
      patients with corneal ulcer.
AB  - PURPOSE: The aim of this study was to determine the long-term treatment efficacy
      of glycerine-preserved human amniotic membrane transplantation in patients
      suffering from corneal ulcers. METHODS: This was a retrospective, non-controlled,
      monocentric analysis. Included were patients with corneal ulcers that were non
      responsive to ointment or contact lenses and had been treated by amniotic
      membrane transplantation with either the overlay or sandwich procedure. Analysis
      parameters were visual acuity before and following treatment, recurrence rate and
      subjective comfort at the last follow-up. RESULTS: Of the 371 amniotic membrane
      transplantations that were conducted, 135 surgical treatments in 108 patients
      (51.9% male, 48.1% female; mean age 63.7 years) met the inclusion criteria. In
      total, 99 overlay and 36 multilayer amniotic membrane transplantations were
      performed. The follow-up period was 47.5 +/- 66.7 weeks (mean +/- SD). The
      recurrence rate at the last follow-up was 47.8% with overlay membranes and 51.8%
      with the sandwich technique. There was no significant change in best-corrected
      visual acuity following treatment with overlays (p = 0.219) or sandwich procedure
      (p = 0.703). At the last follow-up, 72.1% (overlay) and 78.3% (sandwich) of the
      patients reported either no pain or increased comfort. CONCLUSION: The recurrence
      rates and changes in visual acuity following overlay or sandwich amniotic
      membrane transplantation in patients suffering from corneal ulcer were lower than
      reported elsewhere in the literature. More than half of the patients profited
      from each of the amniotic membrane transplantation techniques with respect to
      recurrence and postoperative comfort.

PMID- 25773447
TI  - Cost-effective analysis of topical chlorhexidine in hematologic patients at risk
      for oral mucositis.
AB  - OBJECTIVE: The aim of this study was to explore whether management of mucositis
      with Chlorhexidine (CHX) mouthwash could be a cost-effective method to decrease
      the risk of mortality and economic burden in hemato-oncologic or hematopoietic
      stem cell transplantation (HSCT) patients. METHODS: A cost-effectiveness analysis
      model of prophylactic CHX mouthwash use versus no-CHX mouthwash use for the
      prevention of oral mucositis was developed for patients undergoing cytotoxic
      therapy or HSCT. The outcome variable was survival. The primary variables were
      CHX mouthwash use, probability of mucositis, probability of increased hospital
      stay, and length of hospital stay. Probability and cost data were obtained from
      the literature. RESULTS: Our analysis selected CHX mouthwash use during
      anticancer treatment as the preferred strategy for the base-case analysis as
      compared to no CHX mouthwash (marginal value 0.032). There was a $14,391 cost
      difference per patient between the two strategies. CONCLUSION: The results of
      this study suggest that CHX mouthwash use during anticancer treatment results in
      an increased survival and decreased cost for the population studied. Using our
      base-case data, an additional 32 of every 1,000 hemato-oncologic or HSCT patients
      will survive when employing the preferred strategy of prophylactic CHX mouthwash.
      CLINICAL RELEVANCE: CHX mouthwash should be offered for hematologic patients
      undergoing HSCT or administered with chemotherapy.

PMID- 25773448
TI  - Neurotoxicity of various root canal sealers on rat sciatic nerve: an
      electrophysiologic and histopathologic study.
AB  - OBJECTIVES: The aim of this study was to compare the neurotoxicity of various
      root canal sealers on rat sciatic nerve by electrophysiologic and histopathologic
      analyses. MATERIALS AND METHODS: A total of 40 male rats were randomly divided
      into five groups: Control, AH Plus, GuttaFlow, Sealapex and Smartpastebio.
      Sciatic nerves of the rats were uncovered using the surgical procedures, and the
      prepared sealers were then applied on nerves with a polyethylene tube vehicle for
      15 days. Nerve potentials were recorded at initial exposure, 5, 30 and 120 min
      (early phase), and 15 days (late phase) by an electrophysiologic analysis system
      for all groups. The obtained measurements were then used to calculate the nerve
      conduction velocities (NCV). Subsequently, all rats were sacrificed, and their
      sciatic nerves were removed for histopathologic analysis. Statistical analysis
      was performed using the Kruskal-Wallis and Mann-Whitney U tests for intergroup
      variables and the Friedman and Wilcoxon test for intragroup variables.
      Statistical significance was set at P < 0.05. RESULTS: There was no significant
      difference between early and late phase results in the control group. This group
      showed little or no lasting damage to nerve tissue. All sealers decreased the NCV
      in the early phase time periods, but this decrease was only statistically
      significant in the AH Plus group at 120-min time period (P < 0.0125). During the
      late phase, the AH Plus and GuttaFlow groups almost reached initial NCV values,
      and it was lower than the initial values in the Sealapex and Smartpastebio
      groups. However, this decrease was not statistically significant. When intergroup
      comparisons were performed, statistically significant differences occurred at 30
      min in the Sealapex group and 120 min in the AH Plus group compared with the
      control group (P < 0.0125). All sealers induced neurotoxicity as a result of
      degenerative and inflammatory responses of nerve tissue in histologic analysis.
      Histologic analysis revealed Sealapex and GuttaFlow to be the most and least
      neurotoxic, respectively. CONCLUSIONS: All tested root canal sealers exhibited a
      variable degree of neurotoxicity depending on their chemical compositions.
      CLINICAL RELEVANCE: Apical extrusion of endodontic filling materials may cause
      undesired consequences, such as inflammation and severe neurotoxic damage;
      therefore, extrusion factor plays an important role during the root canal
      treatment.

PMID- 25773446
TI  - Extracellular vesicles, tissue factor, cancer and thrombosis - discussion themes
      of the ISEV 2014 Educational Day.
AB  - Although the association between cancer and venous thromboembolism (VTE) has long
      been known, the mechanisms are poorly understood. Circulating tissue factor
      bearing extracellular vesicles have been proposed as a possible explanation for
      the increased risk of VTE observed in some types of cancer. The International
      Society for Extracellular Vesicles (ISEV) and International Society on Thrombosis
      and Haemostasis (ISTH) held a joint Educational Day in April 2014 to discuss the
      latest developments in this field. This review discusses the themes of that event
      and the ISEV 2014 meeting that followed. 

PMID- 25773449
TI  - Pain after single-visit root canal treatment with two single-file systems based
      on different kinematics--a prospective randomized multicenter clinical study.
AB  - OBJECTIVES: The aim of this study is to evaluate the posttreatment pain after
      instrumentation of root canals with a single-file reciprocating (RECIPROC, VDW,
      Germany) or rotary (One Shape, MicroMega, France) file system. MATERIALS AND
      METHODS: Six hundred forty patients were assessed for eligibility, and 624
      patients were included in this study. The teeth were randomly allocated to one of
      the instrumentation protocols. The teeth underwent routine root canal treatment
      after which patients were discharged with a questionnaire to gather data about
      the incidence (yes/no), nature (mild, moderate, or severe), and duration of pain
      (days). The data were analyzed using statistical analyses (preoperative pain
      scores by Mann-Whitney U test, incidence and intensity of pain by chi-squared
      test, intake of analgesics, and duration of pain by Student's t test) with P =
      0.05. RESULTS: Pain analysis was performed for 605 patients (311 males and 294
      females) as 5 patients were excluded due to sealer extrusion and 14 were lost to
      follow-up. The mean age of the patients was 31 +/- 2 years. There was significant
      difference in the incidence of postoperative pain (P < 0.001). There was
      significant difference in the number of patients who had mild (P = 0.001),
      moderate (P = 0.002), and severe (P = 0.001) pain between the two groups.
      Intensity of pain showed significant difference, with patients in the One Shape
      group (40.5 %) reporting more values of severe pain (P = 0.002); the percentage
      of patients who took analgesics was significantly higher in the One Shape group
      (40.5 %) than in the Reciproc group (19.3 %) (P = 0.002). There was no
      significant difference in the duration of postoperative pain between the two
      groups when the pain was mild (P = 0.301), but One shape showed significantly
      longer duration of moderate (P = 0.001) and severe pain (P = 0.002). CONCLUSIONS:
      Reciproc showed significantly less intensity and duration of posttreatment pain
      compared to One Shape. CLINICAL RELEVANCE: Reciprocation movement offers a more
      predictable and safer approach of root canal preparation, in addition to
      producing less postoperative pain. The need for patients to take analgesics may
      reduce following this approach.

PMID- 25773450
TI  - The write stuff: A proactive approach to increasing academics' writing skills and
      outcomes.
AB  - An important way to advance the profession of nursing, to promote best practice
      and to improve the quality of nursing care, is for nurses to publish. A
      publication track record is necessary to gain competitive research funding, build
      knowledge, disseminate new insights and advance the profession. However,
      academics often experience obstacles in publishing ranging from a pervasive
      teaching culture, lack of confidence in writing, and lack of strategies to write
      more strategically. The benefits of writing retreats have been discussed within
      the nursing and other academic literature but the specifics about the method as
      well as the unplanned benefits have not been explored. More exploration and
      discussion is needed about factors assisting writers to complete papers and
      successfully publish. This paper discusses a novel intervention which aimed to
      seed the beginnings of a flourishing scholarly community at a regional Queensland
      University. The paper also presents qualitative and quantitative evaluation data.

PMID- 25773451
TI  - [Orotracheal intubation and temporomandibular disorder: a longitudinal controlled
      study].
AB  - BACKGROUND AND OBJECTIVES: To determine the incidence of signs and symptoms of
      temporomandibular disorder in elective surgery patients who underwent orotracheal
      intubation. METHODS: This was a longitudinal controlled study with two groups.
      The study group included patients who underwent orotracheal intubation and a
      control group. We used the American Academy of Orofacial Pain questionnaire to
      assess the temporomandibular disorder signs and symptoms one-day postoperatively
      (T1), and the patients' baseline status prior to surgery (T0) was also recorded.
      The same questionnaire was used after three months (T2). The mouth opening
      amplitude was measured at T1 and T2. We considered a p value of less than 0.05 to
      be significant. RESULTS: We included 71 patients, with 38 in the study group and
      33 in the control. There was no significant difference between the groups in age
      (study group: 66 [52.5-72]; control group: 54 [47-68]; p=0.117) or in their
      belonging to the female gender (study group: 57.9%; control group: 63.6%;
      p=0.621). At T1, there were no statistically significant differences between the
      groups in the incidence of mouth opening limitation (study group: 23.7% vs.
      CONTROL GROUP: 18.2%; p=0.570) or in the mouth opening amplitude (study group: 45
      [40-47] vs. CONTROL GROUP: 46 [40-51]; p=0.278). At T2 we obtained similar
      findings. There was no significant difference in the affirmative response to all
      the individual questions in the American Academy of Orofacial Pain questionnaire.
      CONCLUSIONS: In our population, the incidence of signs and symptoms of
      temporomandibular disorder of muscular origin was not different between the
      groups.

PMID- 25773452
TI  - Endoplasmic reticulum stress participates in the progress of senescence of bone
      marrow-derived mesenchymal stem cells in patients with systemic lupus
      erythematosus.
AB  - Previous studies suggested that the senescence of bone marrow mesenchymal stem
      cells (BM-MSCs) played an important role in the pathological process of systemic
      lupus erythematosus (SLE). However, the molecular mechanisms that govern this
      phenomenon have not been fully elucidated. Recent studies reported the activation
      of endoplasmic reticulum stress (ERS) participated in the growth arrest in G1
      phase of cell cycle. In this study, we aimed to investigate whether ERS would
      induce the senescence of BM-MSCs from SLE patients. We found that there was
      increased expression of Glucose Regulated Protein 78 (GRP 78) in BM-MSCs from SLE
      patients, which indicated the activation of ERS in BM-MSCs from SLE patients.
      Accumulation of p27 was also found in BM-MSCs from SLE patients. Interestingly,
      as a chemical chaperone helping the correct folding of proteins, 4-phenylbutyric
      acid (4-PBA) partly rescued the senescence of BM-MSCs from SLE patients and
      alleviated the level of p27. These results implicated ERS-mediated senescence as
      a critical determinant of BM-MSCs from SLE patients. 

PMID- 25773453
TI  - Quantitative techniques for imaging cells and tissues.

PMID- 25773454
TI  - Uncultured bone marrow mononuclear cells delay the dedifferentiation of
      unexpanded chondrocytes in pellet culture.
AB  - Uncultured bone marrow mononuclear cells (BMMC) were recently used to
      successfully repair damaged cartilage. However, the effect of BMMCs on the
      proliferation and differentiation of chondrocytes that are critical to cartilage
      repair is unclear. Here, we investigate the influence of BMMCs on chondrocyte
      dedifferentiation in pellet culture. We isolated and mixed BMMCs and chondrocytes
      in a 1:1 (BMMC/C) ratio and cultured in pellets (1.6 * 10(6) cells per pellet)
      for 2, 4, or 8 weeks. Chondrocyte differentiation was evaluated using
      macrography, histological examination, immunohistochemistry and gene expression
      analysis. While a transparent and smooth surface was observed in both BMMC/C and
      chondrocyte cultures over time, the former was smaller in size after 2 and 4
      weeks of culture. Interestingly, after 8 weeks, BMMC/C cultures became
      significantly larger than chondrocyte cultures (P = 0.003). The distribution of a
      cartilage-specific extracellular matrix (ECM), that includes components like
      glycosaminoglycan (GAG) and type II collagen, was gradually reduced in
      chondrocyte cultures. On the other hand, while we found no obvious differences in
      the ECM in BMMC/C cultures between 2 and 4 weeks in vitro, after 8 weeks the
      concentration of ECM components decreased significantly. Further, we detected an
      upregulation of cartilage-specific genes in BMMC/C cultures, when compared with
      chondrocytes. Altogether, we demonstrate that co-culture with BMMCs delays the
      dedifferentiation of chondrocytes in pellet cultures in vitro. This suggests that
      uncultured BMMC, which can be quickly and safely obtained, could serve as a
      potential alternative cell source for engineering of cartilage tissue. 

PMID- 25773455
TI  - Analysis of the intensity of immune cell infiltration and immunoreactivity of
      RCAS1 in diffuse large B-cell lymphoma of the palatine tonsil and its
      microenvironment.
AB  - Non-Hodgkin lymphoma of Waldeyer's ring constitutes a small percentage of cases
      of palatine tonsil malignancies and its precise etiology remains unknown. RCAS1
      (receptor cancer-binding antigen expressed on SiSo cells) has been demonstrated
      to be associated with poor prognosis, the development of lymph node metastases
      and participation in tumor microenvironment remodeling. Our aim is to analyze the
      potential role of RCAS1 expression in the tumor and tumor microenvironment in the
      development of early-stage palatine tonsil B-cell lymphomas. We selected 20
      patients and analyzed tissue samples from the lymphoma and tumor microenvironment
      of each patient and from a reference group of 20 patients with chronic
      tonsillitis. The presence of RCAS1 protein immunoreactivity was demonstrated in
      65% of the examined tissue samples of diffuse large B-cell lymphoma and in 25% of
      the analyzed stromata in which it was exhibited by CD68-positive cells identified
      as macrophages and dispersed throughout the stroma. RCAS1 immunoreactivity in the
      lymphoma tissue samples remained at a level comparable with that of the reference
      and was significantly higher in these samples than in those from the stroma.
      Chronic inflammation of the palatine tonsils thus results in intensive
      infiltration by various types of immune system cells and in excessive RCAS1
      immunoreactivity, both of which confirm the important regulatory role of RCAS1 in
      the immune response in the mucosa-associated lymphatic tissue of Waldeyer's ring.
      RCAS1 seems to be involved in creating tumor-induced inflammation in the tumor
      and its microenvironment.

PMID- 25773456
TI  - Personality Trait Differences Between Young and Middle-Aged Adults: Measurement
      Artifacts or Actual Trends?
AB  - A growing body of research demonstrates that older individuals tend to score
      differently on personality measures than younger adults. However, recent research
      using item response theory (IRT) has questioned these findings, suggesting that
      apparent age differences in personality traits merely reflect artifacts of the
      response process rather than true differences in the latent constructs.
      Conversely, other studies have found the opposite-age differences appear to be
      true differences rather than response artifacts. Given these contradictory
      findings, the goal of the present study was to examine the measurement
      equivalence of personality ratings drawn from large groups of young and middle
      aged adults (a) to examine whether age differences in personality traits could be
      completely explained by measurement nonequivalence and (b) to illustrate the
      comparability of IRT and confirmatory factor analysis approaches to testing
      equivalence in this context. Self-ratings of personality traits were analyzed in
      two groups of Internet respondents aged 20 and 50 (n = 15,726 in each age group).
      Measurement nonequivalence across these groups was negligible. The effect sizes
      of the mean differences due to nonequivalence ranged from -.16 to .15. Results
      indicate that personality trait differences across age groups reflect actual
      differences rather than merely response artifacts.

PMID- 25773458
TI  - Impact of ACA on the Dinner-for-Three Dynamic.
AB  - The Patient Protection and Affordable Care Act (ACA) aims to expand coverage to
      the previously uninsured, improve the quality of coverage, and help eliminate
      inefficiencies in the health care market. We evaluated the implications of ACA on
      the drug industry by examining the impact on the "Dinner-for-Three" dynamic in
      our health care system. We can think of our system as an odd dinner party in
      which one person pays (the insurer), one orders the meal (the physician), and yet
      another eats the meal (the patient). This dynamic requires us to examine each
      stakeholder and how they interact with one another to assess the impact of the
      ACA. Of the 6.7 million initial exchange enrollees, ~3.8 million subjects were
      previously uninsured. A higher percentage of these enrollees are using their
      pharmacy benefit, and they are disproportionately filling prescriptions for
      specialty drugs relative to those covered in employer-sponsored plans. Formulary
      designs in exchange plans are passing on higher cost-sharing for prescription
      drugs to the patient. ACA has also resulted in the development of accountable
      care organizations (ACOs); these organizations may play a role going forward in
      the management of drug spending and the development of formularies and protocols
      that impact drug prescribing. Payers are tightening control over drug spending
      and are finding physicians and physician groups increasingly less reluctant
      allies in doing so. Patients are faced by more complexity than ever in the health
      care system and are expected to take a more active role in responsibly managing
      the cost of their care. It is increasingly critical that drug manufacturers
      develop robust value propositions and communicate that value to all stakeholders.
      They should re-evaluate trial investment decisions and consider changes in price
      setting, rebates (how much and to whom), copay programs, and physician and
      patient support programs in light of changing market needs. 

PMID- 25773457
TI  - Salivary cortisol results obtainable within minutes of sample collection
      correspond with traditional immunoassays.
AB  - PURPOSE: Cortisol is frequently assayed as a stress-responsive biomarker which
      changes over the course of minutes to meet the demands of a person's social
      context. Salivary cortisol is often used as a noninvasive sampling method that
      possesses important health implications. A critical barrier to psychobiological
      research that involves salivary cortisol is a time delay of days to months before
      cortisol results are obtained via immunoassay, long after the person is no longer
      proximate to the social context in which they provided the sample. The present
      study was designed to address this critical barrier through creation of a lateral
      flow test (LFT) cortisol device capable of measuring salivary cortisol within
      minutes of sample collection. The LFT is frequently used within commercial point
      of-care settings to obtain rapid answers to the presence/absence of a biomarker.
      The present study extends the LFT into the research domain by presenting
      performance characteristics of a quantitative LFT that measures salivary cortisol
      within 20 minutes of sample collection. METHODS: Saliva samples from 29 adults
      (15 men) were obtained in the morning and afternoon by using Passive Drool and
      then the Super.SAL Extra Collection Device (hereafter Super.SAL) and later
      assayed with LFT and a commercially available enzyme immunoassay. FINDINGS:
      Results indicate the LFT correlated well with these collection methods (R = 0.872
      with Super . SAL, R = 0.739 with Passive Drool, P < 0.0001) and at comparable
      levels to correspondence of Super . SAL with Passive Drool (R = 0.798, P <
      0.0001) which were measured with the same assay. IMPLICATIONS: These results open
      an exciting new possibility to integrate this technologic advance into stress
      research, including knowing and potentially changing the person's social context
      in a time-sensitive manner. Methodological improvements such as this have the
      possibility of refining conceptual models of stress reactivity and regulation.

PMID- 25773459
TI  - Mast Cell Activation Disease and Microbiotic Interactions.
AB  - PURPOSE: This article reviews the diagnostically challenging presentation of mast
      cell activation disease (MCAD) and current thoughts regarding interactions
      between microbiota and MCs. METHODS: A search for all studies on interactions
      between mast cells, mast cell activation disease, and microbiota published on
      pubmed.gov and scholar.google.com between 1960 and 2015 was conducted using the
      search terms mast cell, mastocyte, mastocytosis, mast cell activation, mast cell
      activation disease, mast cell activation syndrome, microbiome, microbiota. A
      manual review of the references from identified studies was also conducted.
      Studies were excluded if they were not accessible electronically or by
      interlibrary loan. FINDINGS: Research increasingly is revealing essential
      involvement of MCs in normal human biology and in human disease. Via many
      methods, normal MCs-present sparsely in every tissue-sense their environment and
      reactively exert influences that, directly and indirectly, locally and remotely,
      improve health. The dysfunctional MCs of the "iceberg" of MCAD, on the other
      hand, sense abnormally, react abnormally, activate constitutively, and sometimes
      (in mastocytosis, the "tip" of the MCAD iceberg) even proliferate neoplastically.
      MCAD causes chronic multisystem illness generally, but not necessarily, of an
      inflammatory +/- allergic theme and with great variability in behavior among
      patients and within any patient over time. Furthermore, the range of signals to
      which MCs respond and react include signals from the body's microbiota, and
      regardless of whether an MCAD patient has clonal mastocytosis or the bulk of the
      iceberg now known as MC activation syndrome (also suspected to be clonal but
      without significant MC proliferation), dysfunctional MCs interact as
      dysfunctionally with those microbiota as they interact with other human tissues,
      potentially leading to many adverse consequences. IMPLICATIONS: Interactions
      between microbiota and MCs are complex at baseline. The potential for both
      pathology and benefit may be amplified when compositionally variant microbiota
      interact with aberrant MCs in various types of MCAD. More research is needed to
      better understand and leverage these interactions.

PMID- 25773460
TI  - New techniques for augmenting saliva collection: bacon rules and lozenge drools.
AB  - PURPOSE: Saliva is a reliable, noninvasive, and cost-effective alternative to
      biomarkers measured in other biological fluids. Within certain populations,
      saliva sampling may be difficult because of insufficient saliva flow, which may
      compromise disease diagnosis or research integrity. Methods to improve flow rates
      (eg, administering citric acid, chewing gum, or collecting cotton) may compromise
      biomarker integrity, especially if the methods involve the presence of a
      collection aid in the oral cavity. Anecdotal strategies (eg, looking at pictures
      of food or imagining food) have not been evaluated to date. In this study, we
      evaluate whether 2 novel collection techniques improve saliva flow or interfere
      with assay of common biomarkers (ie, cortisol, dehydroepiandrosterone, and
      testosterone). We evaluate an over-the-counter anhydrous crystalline maltose
      lozenge intended to increase saliva production for patients with xerostomia long
      after the lozenge dissolves. We then evaluate whether the smell of freshly cooked
      bacon stimulates a pavlovian-type reflex. METHODS: Saliva was collected from 27
      healthy young adults (aged 20-34 years; 12 men) on a basal day and a lozenge day,
      providing 5 samples at 15-minute intervals. Twenty participants then returned for
      the bacon day condition, providing 2 saliva samples with an interval of 15
      minutes between samples. Collection times required to generate 2 mL of saliva
      across collection strategies were recorded, and then saliva samples were assayed
      for cortisol, dehydroepiandrosterone, and testosterone. FINDINGS: Repeated
      analysis of variance measures revealed that both the lozenges and bacon
      significantly decreased collection time compared with the passive drool
      collection on the basal day. No significant effects were found related to the
      quantification of cortisol, testosterone, or dehydroepiandrosterone when
      comparing lozenge or bacon to the basal day. In addition, bivariate correlations
      revealed that concentrations from time-matched control samples correlated
      significantly with concentrations from the lozenge and bacon conditions.
      IMPLICATIONS: These results indicate that both the lozenge and smelling bacon
      improve saliva collection times and that neither technique interferes with
      salivary hormone concentrations. This study reveals new methods to augment saliva
      collection strategies.

PMID- 25773461
TI  - Clinically significant differences in acute pain measured on self-report pain
      scales in children.
AB  - OBJECTIVES: The objective was to determine the minimum and ideal clinically
      significant differences (MCSD, ICSD) in pain intensity in children for the Faces
      Pain Scale-Revised (FPS-R) and the Color Analog Scale (CAS) and to identify any
      differences in these estimates based on patient characteristics. METHODS: This
      was a prospective study of children aged 4 to 17 years with acute pain presenting
      to two urban pediatric emergency departments. Participants self-reported their
      pain intensity using the FPS-R and CAS and qualitatively described their changes
      in pain. Changes in pain score reported using the FPS-R and CAS that were
      associated with "a little less" and "much less" pain (MCSD and ICSD,
      respectively) were identified using a receiver operating characteristic-based
      method and expressed as raw change score and percent reductions. Estimates of
      MCSD and ICSD were determined for each category of initial pain intensity (mild,
      moderate, and severe) and patient characteristics (age, sex, and ethnicity). Post
      hoc exploratory analyses evaluated categories of race, primary language, and
      etiology of pain. RESULTS: A total of 314 children with acute pain were enrolled;
      mean (+/-SD) age was 9.8 (+/-3.8) years. The FPS-R raw change score and percent
      reduction MCSD estimates were 2/10 and 25%, with ICSD estimates of 3/10 and 60%.
      For the CAS, raw change score and percent reduction MCSD estimates were 1/10 and
      15%, with ICSD estimates of 2.75/10 and 52%. For both scales, raw change score
      and percent reduction estimates of the MCSD remained unchanged in children with
      either moderate or severe pain. For both scales, estimates of ICSD were not
      stable across categories of initial pain intensity. There was no difference in
      MCSD or ICSD based on age, sex, ethnicity, race, primary language, or etiology of
      pain. CONCLUSIONS: The MCSD estimates can be expressed as raw change score and
      percent reductions for the FPS-R and CAS. These estimates appear stable for
      children with moderate to severe pain, irrespective of age, sex, and ethnicity.
      Estimates of ICSD were not stable across different categories of initial pain
      intensity, therefore limiting their potential generalizability.

PMID- 25773462
TI  - High endemic rates of OXA-23-producing carbapenem-resistant Acinetobacter
      baumannii isolates caused by the persistence of major clones in hospitals in a
      Brazilian city 5 years after an outbreak.

PMID- 25773463
TI  - New insights into the toxicity mechanism of octanoic and decanoic acids on
      Saccharomyces cerevisiae.
AB  - Octanoic (C8) and decanoic (C10) acids are produced in hypoxic conditions by the
      yeast Saccharomyces cerevisiae as by-products of its metabolism and are
      considered fermentation inhibitors in the presence of ethanol at acidic pH. This
      study aims to broaden our understanding of the physiological limits between
      toxicity and ester production in yeast cells. To this end, the non-inhibitory
      concentration (NIC) and maximum inhibitory concentration (MIC) values were first
      established for C8 and C10 at physiological pH (5.8) without ethanol. The results
      showed that when these acids were added to culture medium at these values, they
      tended to accumulate in different cellular fractions of the yeast. While C8 was
      almost entirely located in the cell wall fraction, C10 was found in the
      endocellular fraction. Cell fatty acid detoxification was also different; while
      the esterification of fatty acids was more efficient in the case of C10, the
      peroxisome was activated regardless of which fatty acid was added. Furthermore,
      the study of the Pdr12 and Tpo1 transporters that evolved during the
      detoxification process revealed that C8 was mostly expelled by the Pdr12 carrier,
      which was related to higher beta-oxidative damage in the presence of endocellular
      C10. C10 is more toxic at lower concentrations than C8. Although they are
      produced by yeast, the resulting intracellular medium-chain fatty acids (MCFAs)
      caused a level of toxicity which promoted cell death. However, MCFAs are involved
      in the production of beverage flavours.

PMID- 25773464
TI  - Roles of oxidative stress and endoplasmic reticulum stress in selenium deficiency
      induced apoptosis in chicken liver.
AB  - Oxidative stress and endoplasmic reticulum (ER) stress are involved in different
      types of stress-induced injuries. The aim of the present study was to evaluate
      the effect of Se deficiency on oxidative stress, ER stress and apoptosis in
      chicken livers. Chickens (1 day old, n = 180) were randomly divided into two
      groups: the L group [fed with a Se-deficient (Se 0.033 mg/kg) diet] and the
      control group [fed with a normal (Se 0.2 mg/kg) diet]. Factor-associated
      oxidative stress, catalase (CAT) activity, H2O2 production and the inhibition of
      hydroxyl radicals (.OH) in the chicken liver were determined on days 15, 25, 35,
      45, 55 and 65, respectively. In addition, ER stress-related genes (GRP78, GRP94,
      ATF4, ATF6 and IRE) and apoptosis-related genes (caspase3 and Bcl-2) were
      examined by fluorescence quantitative PCR or western blot analysis. Apoptosis
      levels were also measured using ultrastructural observations and the TdT-mediated
      dUTP nick end labeling assay. The results showed that CAT activity and .OH
      inhibition were decreased and that H2O2 production was increased in the low-Se
      group, which demonstrated that oxidative stress occurred in the chicken liver.
      The ER stress-related genes (GRP78, GRP94, ATF4, ATF6 and IRE) and the apoptosis
      related gene caspase3 were increased (p < 0.05), while Bcl-2 was decreased (p <
      0.05) by Se deficiency. In addition, apoptosis and ER lesions were observed by
      ultrastructural observations of the chicken liver in the low-Se group. The level
      of apoptosis and the number of apoptotic cells increased with time. These results
      indicated that the oxidative-ER stress pathway participates in Se deficiency
      induced apoptosis in the chicken liver.

PMID- 25773465
TI  - Menthol concentration in topical cold gel does not have significant effect on
      skin cooling.
AB  - BACKGROUND: Topical menthol gels are used in the treatment of various pain
      conditions. However, the effect of the menthol concentration to skin cooling or
      cooling sensation is not clear. We hypothesized that increasing menthol
      concentration enhances skin cooling and causes elevated cooling sensation.
      METHODS: Ten healthy male volunteers (age range 25-30 years) were recruited for
      this study. Application of three gels with different menthol concentrations
      (0.5%, 4.6% and 10.0%) was tested in random sequence on the left thigh of the
      subjects. Skin cooling was recorded with a digital infrared camera (FLIR Systems
      Inc., USA), and cooling sensation was measured with the visual analogue scale
      rating. RESULTS: All gels decreased skin temperature significantly (P < 0.05) at
      least for one hour. However, the variation in menthol concentration seemed not to
      have a significant effect on skin cooling. Subjects experienced that gel with
      4.6% menthol concentration caused significantly stronger cooling effect than 0.5%
      and 10.0% gels. Gel application had no significant effect on skin temperature in
      surrounding skin areas. CONCLUSION: In contrast to our hypothesis, menthol
      concentration was not connected to skin cooling, while moderate menthol
      concentration of 4.6% may induce stronger cooling sensation compared to low
      (0.5%) or high (10.0%) concentration gels.

PMID- 25773466
TI  - A two layers monodomain model of cardiac electrophysiology of the atria.
AB  - Numerical simulations of the cardiac electrophysiology in the atria are often
      based on the standard bidomain or monodomain equations stated on a two
      dimensional manifold. These simulations take advantage of the thinness of the
      atrial tissue, and their computational cost is reduced, as compared to three
      dimensional simulations. However, these models do not take into account the
      heterogeneities located in the thickness of the tissue, like discontinuities of
      the fiber direction, although they can be a substrate for atrial arrhythmia
      (Hocini et al., Circulation 105(20):2442-2448, 2002; Ho et al., Cardiovasc Res
      54(2):325-336, 2002; Nattel, Nature 415(6868):219-226, 2002). We investigate a
      two-dimensional model with two coupled, superimposed layers that allows to
      introduce three-dimensional heterogeneities, but retains a reasonable
      computational cost. We introduce the mathematical derivation of this model and
      error estimates with respect to the three-dimensional model. We give some
      numerical illustrations of its interest: we numerically show its convergence for
      vanishing thickness, introduce an optimization process of the coupling
      coefficient and assess its validity on physiologically relevant geometries. Our
      model would be an efficient tool to test the influence of three-dimensional fiber
      direction heterogeneities in reentries or atrial arrhythmia without using three
      dimensional models. 

PMID- 25773467
TI  - Modelling the dynamics of traits involved in fighting-predators-prey system.
AB  - We study the dynamics of a predator-prey system where predators fight for
      captured prey besides searching for and handling (and digestion) of the prey.
      Fighting for prey is modelled by a continuous time hawk-dove game dynamics where
      the gain depends on the amount of disputed prey while the costs for fighting is
      constant per fighting event. The strategy of the predator-population is
      quantified by a trait being the proportion of the number of predator-individuals
      playing hawk tactics. The dynamics of the trait is described by two models of
      adaptation: the replicator dynamics (RD) and the adaptive dynamics (AD). In the
      RD-approach a variant individual with an adapted trait value changes the
      population's strategy, and consequently its trait value, only when its payoff is
      larger than the population average. In the AD-approach successful replacement of
      the resident population after invasion of a rare variant population with an
      adapted trait value is a step in a sequence changing the population's strategy,
      and hence its trait value. The main aim is to compare the consequences of the two
      adaptation models. In an equilibrium predator-prey system this will lead to
      convergence to a neutral singular strategy, while in the oscillatory system to a
      continuous singular strategy where in this endpoint the resident population is
      not invasible by any variant population. In equilibrium (low prey carrying
      capacity) RD and AD-approach give the same results, however not always in a
      periodically oscillating system (high prey carrying-capacity) where the trait is
      density-dependent. For low costs the predator population is monomorphic (only
      hawks) while for high costs dimorphic (hawks and doves). These results illustrate
      that intra-specific trait dynamics matters in predator-prey dynamics. 

PMID- 25773468
TI  - Changes and determination of dosing recommendations for medicinal products
      recently authorised in the European Union.
AB  - INTRODUCTION: The quantity and quality of data for determining the dose and
      treatment schedule of medicinal products is directly related to how safe and
      efficacious these medicines are and how successful they can be used to treat
      patients. AREAS COVERED: This review provides an analysis of dose-related label
      modifications of recently approved drugs. It shows which areas could benefit from
      a better dose-exposure-response understanding, both during initial assessment and
      after marketing authorisation. This analysis highlights regulators'
      considerations in dosage evaluations and provides reflections for drug developers
      on how to ensure best possible dose selection in the interest of the patients.
      EXPERT OPINION: Using modelling and simulation, pharmacogenomics, population
      pharmacokinetics, physiologically based pharmacokinetic models and drug-drug
      interaction studies in conjunction with well-designed clinical trials will
      improve the understanding of the pharmacology of medicines, of the physiology of
      the disease and of the dose-exposure-response relationship during drug
      development. More focus should be given to the investigation of dose and regimens
      for special populations before applying for marketing authorisation.
      Consequently, regulators could review dose-exposure-response data with more
      certainty and better define dose recommendations in the label.

PMID- 25773469
TI  - Association between mother-child sexual communication and HPV vaccine uptake.
AB  - OBJECTIVE: To examine the association between mother-child communication about
      sex, sexually transmitted diseases (STDs), and contraception/condoms and HPV
      vaccine uptake by gender. METHODS: Women (n = 1372) with >= 1 child aged 9-17
      years receiving care in reproductive health clinics in Southeast Texas were asked
      to complete a self-administered questionnaire between September 2011 and October
      2013. RESULTS: The majority of mothers with >= 1 eligible daughter (n = 886)
      reported having talked about 'sex' (77.7%), 'STDs' (76.6%) and 'contraception'
      (73.2%) with their daughters. The respective figures for mothers with >= 1 son (n
      = 836) were 68.8%, 69.0% and 65.3%. Mothers who discussed sex, STDs, or
      contraception with their daughters compared to those who did not were more likely
      to report that their daughter initiated (>= 1 dose) HPV vaccination after
      adjusting for confounders (all p < .05). Similarly, mother-son discussions about
      STDs or condoms, but not sex, were associated with HPV vaccine initiation for
      their sons compared to those who did not discuss these topics. These associations
      were not significant with regard to HPV vaccine completion (3 doses) for neither
      daughters nor sons. CONCLUSION: Mother-child communication on STDs and
      contraception/condoms is associated with HPV vaccine initiation, but not
      completion, among both daughters and sons.

PMID- 25773470
TI  - Does time pressure create barriers for people to receive preventive health
      services?
AB  - OBJECTIVE: Regular use of recommended preventive health services can promote good
      health and prevent disease. However, individuals may forgo obtaining preventive
      care when they are busy with competing activities and commitments. This study
      examined whether time pressure related to work obligations creates barriers to
      obtaining needed preventive health services. METHODS: Data from the 2002-2010
      Medical Expenditure Panel Survey (MEPS) were used to measure the work hours of
      61,034 employees (including 27,910 females) and their use of five preventive
      health services (flu vaccinations, routine check-ups, dental check-ups,
      mammograms and Pap smear). Multivariable logistic regression analyses were
      performed to test the association between working hours and use of each of those
      five services. RESULTS: Individuals working long hours (>60 per week) were
      significantly less likely to obtain dental check-ups (OR=0.81, 95% CI: 0.72-0.91)
      and mammograms (OR=0.47, 95% CI: 0.31-0.73). Working 51-60 h weekly was
      associated with less likelihood of receiving Pap smear (OR=0.67, 95% CI: 0.46
      0.96). No association was found for flu vaccination. CONCLUSIONS: Time pressure
      from work might create barriers for people to receive particular preventive
      health services, such as breast cancer screening, cervical cancer screening and
      dental check-ups. Health practitioners should be aware of this particular source
      of barriers to care.

PMID- 25773471
TI  - Leisure-time physical activity in relation to occupational physical activity
      among women.
AB  - OBJECTIVE: The objective of this study is to examine the association between
      occupational physical activity and leisure-time physical activity among US women
      in the Sister Study. METHODS: We conducted a cross-sectional study of 26,334
      women who had been employed in their current job for at least 1 year at baseline
      (2004-2009). Occupational physical activity was self-reported and leisure-time
      physical activity was estimated in metabolic equivalent hours per week. Log
      multinomial regression was used to evaluate associations between occupational
      (sitting, standing, manually active) and leisure-time (insufficient, moderate,
      high) activity. Models were adjusted for age, race/ethnicity, education, income,
      geographic region, and body mass index. RESULTS: Only 54% of women met or
      exceeded minimum recommended levels of leisure-time physical activity (moderate
      32% and high 22%). Women who reported sitting (prevalence ratio (PR)=0.82, 95%
      confidence interval (CI): 0.74-0.92) or standing (PR=0.84, 95% CI: 0.75-0.94)
      most of the time at work were less likely to meet the requirements for high
      leisure-time physical activity than manually active workers. Associations were
      strongest among women living in the Northeast and the South. CONCLUSION: In this
      nationwide study, low occupational activity was associated with lower leisure
      time physical activity. Women who are not active in the workplace may benefit
      from strategies to promote leisure-time physical activity.

PMID- 25773472
TI  - Abstinence rates among college cigarette smokers enrolled in a randomized
      clinical trial evaluating Quit and Win contests: The impact of concurrent hookah
      use.
AB  - OBJECTIVE: To examine baseline characteristics and biochemically verified 1-, 4-,
      and 6-month tobacco quit rates among college students enrolled in a Quit and Win
      cessation trial, comparing those who concurrently smoke both hookah and
      cigarettes with those who deny hookah use. METHODS: Analyses were conducted on
      data from 1217 college students enrolled in a Quit and Win tobacco cessation
      randomized clinical trial from 2010-2012. Multivariable logistic regression (MLR)
      analyses examined group differences in baseline characteristics and cotinine
      verified 30-day abstinence at 1, 4, and 6-month follow-up, adjusting for baseline
      covariates. RESULTS: Participants smoked 11.5(+/-8.1) cigarettes per day on
      28.5(+/-3.8) days/month, and 22% smoked hookah in the past 30days. Hookah smokers
      (n=270) were more likely to be male (p<0.0001), younger (p<0.0001), report more
      binge drinking (p<0.0001) and score higher on impulsivity (p<0.001). MLR results
      indicate that hookah users, when compared to non-users, had a 36% decrease in
      odds of self-reported 30-day abstinence at 4-months (OR=0.64, 95% CI=0.45-0.93,
      p=0.02) and a 63% decrease in odds in biochemically verified continuous
      abstinence at 6-months (OR=0.37, CI=0.14-0.99, p=0.05). CONCLUSION: College
      cigarette smokers who concurrently use hookah display several health risk factors
      and demonstrate lower short and long-term tobacco abstinence rates.

PMID- 25773473
TI  - The effects of Pilates exercise training on physical fitness and wellbeing in the
      elderly: A systematic review for future exercise prescription.
AB  - This systematic review aims to summarize the effects of Pilates exercise training
      (PET) in elderly population on physical fitness, balance and fall prevention, and
      its effects on mood states, quality of life and independence in the daily living
      activities. METHODS: Keyword "Pilates" associated with "elderly", "aging" and
      "old subjects" were identified as terms for the literature research in MEDLINE,
      Embase, PubMed, Scopus, PsycINFO and SPORTDiscus. Only studies published in peer
      reviewed journals written in English language were considered. A meta-analysis
      was performed and effect sizes (ES) calculated. RESULTS: 10 studies were
      identified (6 RCTs and 4 uncontrolled trials); age ranged from 60 to 80years.
      Overall, PET showed large ES to improve muscle strength (ES=1.23), walking and
      gait performances (ES=1.39), activities of daily living, mood states and quality
      of life (ES=0.94), moderate to high effect on dynamic balance (ES=0.77), small
      effects on static balance (ES=0.34) and flexibility (ES=0.31), while a small
      effect on cardio-metabolic outcomes (ES=0.07). CONCLUSIONS: PET should be taken
      into account as a way to improve quality of life in the elderly, due to the
      imparted benefits of fall prevention, physical fitness, and mood states. In this
      context, physicians might include PET as a tool for exercise prescriptions for
      the elderly.

PMID- 25773474
TI  - Pannexin-2 is expressed in the human colon with extensive localization in the
      enteric nervous system.
AB  - BACKGROUND: Pannexin-2 (Panx2) is a member of the novel group of membrane
      spanning protein channels present in the central nervous system. Limited studies
      have examined Panx2 in the intestine, where it may have important physiological
      roles. The present study characterized Panx2 expression and localization in the
      human colon in health and disease states. METHODS: Immunofluorescence determined
      Panx2 localization and co-localization, and quantitative real-time PCR and
      Western blot determined gene and protein expression in ulcerative colitis (UC),
      Crohn's disease (CD), and control human colon. KEY RESULTS: Panx2 was widely
      expressed in myenteric and submucosal ganglia, particularly in the cytoplasm of
      neurons. Panx2 was also expressed on smooth muscle of the muscularis and blood
      vessels, some non-lymphoid leukocytes, mast cells, and mucosal epithelial cells.
      Co-localization of Panx2 occurred with beta-tubulin, neuronal nitric oxide
      synthase, substance P, vesicular acetylcholine transporter, and calcitonin gene
      related peptide, indicating widespread Panx2 expression in extrinsic and
      intrinsic neurons. Molecular studies revealed a 3.4-fold higher level of Panx2
      mRNA in ascending compared to sigmoid muscularis (p < 0.05), despite similar
      protein levels. Similarly, UC muscularis showed a 35-fold up-regulation in Panx2
      mRNA, but not in protein (p < 0.05). CONCLUSIONS & INFERENCES: Here, we
      demonstrated the dense expression of Panx2 in the enteric nervous system and the
      co-localization of Panx2 with a spectrum of neuronal markers, indicating that
      Panx2 may be involved in mediating neurotransmission in the colon. The
      substantial increase in Panx2 mRNA in UC muscle but not protein suggests that the
      Panx2 translation process may be disrupted in UC.

PMID- 25773475
TI  - Is pentoxifylline still an option in severe alcoholic hepatitis?

PMID- 25773476
TI  - Dual antiplatelet therapy duration after the placement of a drug-eluting stent:
      what are the data?
AB  - OPINION STATEMENT: The data supporting the immediate use of dual antiplatelet
      therapy (DAPT) post implantation of drug-eluting stents (DESs) is irrefutable.
      DAPT in this early period is necessary to prevent stent thrombosis during
      endothelialization of the stent, a process known to be delayed when DESs are
      placed. In addition, DAPT helps prevent thrombosis from plaque rupture that
      occurs outside of the initial stented area and/or at neo-atherosclerotic lesions
      within a previously coated stent. The ACC/AHA current guidelines (Levine et al. J
      Am Coll Cardiol. 58(24):e44-122, 2011) recommend 12 months of DAPT post DES
      implantation. As the result of several randomized clinical trials (Task Force on
      Myocardial Revascularization of the European Society of Cardio-Thoracic Surgery
      (EACTS) et al. Eur Heart J. 31(20):2501-55, 2010) showing the safety of a shorter
      duration of DAPT, the European Heart Society altered their recommendations to 6
      12 months of DAPT post DES implantation. However, recent data from the DAPT trial
      (Mauri et al. N Engl J Med. 371(23):2156-66, 2014) clearly demonstrated less
      ischemic events with 30 months of DAPT. This trial and others have established
      that an increased DAPT duration increases bleeding risk which, in turn, increases
      subsequent morbidity and mortality. The current conundrum lies in defining the
      optimal time of DAPT post DES to adequately reduce ischemic events while
      minimizing bleeding risks. Future studies are required to better stratify
      patients into low and high risk for both ischemic and bleeding risks to assess
      whether shorter or longer courses of DAPT are the most appropriate for any
      specific patients. Until then, instead of a "one size fits all" approach to
      patients who receive DESs, the treating physician must consider both procedural
      and patient factors when deciding the optimal duration of DAPT for each patient.

PMID- 25773477
TI  - Antimicrobial and antiquorum-sensing studies. Part 3: Synthesis and biological
      evaluation of new series of [1,3,4]thiadiazoles and fused [1,3,4]thiadiazoles.
AB  - New series of [1,3,4]thiadiazoles and fused [1,3,4]thiadiazoles were synthesized.
      The newly synthesized compounds were screened for their antibacterial activity
      against Staphylococcus aureus, Bacillus cereus, and Escherichia coli. Compounds
      3b and 10a displayed the highest activity against E. coli with MIC value of
      78.125 MUg/mL. In addition, compound 10a exhibited the highest activity against
      B. cereus with MIC value of 156.25 MUg/mL. The antifungal activity of these
      compounds was also tested against Candida albicans and Aspergillus flavus 3375.
      Compounds 3b, 5a, 10a, and 12b showed the best activity against A. flavus 3375
      with MIC value of 19.531 MUg/mL. The same compounds were examined for their
      antiquorum-sensing activity against Chromobacterium violaceum ATCC 12472, whereas
      compounds 3b, 5a, and 12b exhibited moderate activity. In vitro cytotoxicity
      testing of compounds 3b,c, 5a, 6a, 10a, and 12a,b against human normal lung
      fibroblast (W138) cell line was performed. The in vivo acute toxicity of the same
      compounds was also tested and the obtained results indicated that compound 10a is
      the least toxic analog. The same compounds were studied for their DNA-binding
      affinity and the obtained results showed that compounds 3b, 10a, and 12a,b have
      moderate DNA-binding affinity.

PMID- 25773478
TI  - HIV status disclosure, depressive symptoms, and sexual risk behavior among HIV
      positive young men who have sex with men.
AB  - The rate of HIV infection among young men who have sex with men (YMSM) is
      increasing in the United States, and targeted research is needed to inform
      interventions aimed at reducing HIV transmission in this population. This study
      aims to understand the association between HIV status disclosure and sexual risk
      behavior among HIV-positive YMSM. A particular focus is given to depressive
      symptoms and their potential role in explaining the association between HIV
      disclosure and sexual risk behavior. In a sample of 991 YMSM receiving care at 20
      clinics across the United States, Univariate and multivariate analyses were
      conducted to explore these associations. Approximately one-half (52.4 %) of
      participants reported disclosing to their current sexual/romantic partner.
      Disclosure to family members was negatively associated with sexual risk behavior.
      Also, depressive symptoms were positively associated with sexual risk behavior.
      We discuss the implications of our findings for future research and intervention.

PMID- 25773479
TI  - A physiologically based pharmacokinetic drug-disease model to predict carvedilol
      exposure in adult and paediatric heart failure patients by incorporating
      pathophysiological changes in hepatic and renal blood flows.
AB  - BACKGROUND AND OBJECTIVE: Chronic diseases are associated with pathophysiological
      changes that could have profound impacts on drug pharmacokinetic behaviour, with
      a potential need to modify the administered drug therapy. It is important to
      acknowledge that most patients with chronic illnesses do not have a single,
      predominant condition but suffer from multiple comorbidities. The rapid
      advancement in physiologically based pharmacokinetic (PBPK) modelling, as well as
      the increasing quantitative knowledge of disease-related pathophysiological
      changes, facilitate building of drug-disease models. However, there are only a
      few published examples of PBPK models incorporating the pathophysiological
      changes that occur with chronic diseases. The objective of this study was to
      develop PBPK models that incorporate the haemodynamic changes in hepatic and
      renal blood flows occurring in chronic heart failure (CHF) and to evaluate these
      changes in adults and children, using carvedilol as a model drug. METHODS: After
      a comprehensive literature search to select the model input parameters, two PBPK
      models were developed. Model 1 was based on human liver and intestinal microsome
      clearances, and model 2 was based on clearance by specific cytochrome P450
      enzymes. After evaluation of both models in healthy adults, the reduced hepatic
      and renal blood flows were incorporated into the developed models to predict
      carvedilol exposure in the adult CHF population. The adult carvedilol models were
      scaled down to children by using Simcyp((r)) (Simcyp Ltd, Sheffield, UK). In
      order to show the impact of reduced organ blood flows on carvedilol disposition,
      the predictions in the CHF population were made with and without reductions in
      organ blood flows. RESULTS: The predictions made by both models in healthy adults
      were comparable and within the 2-fold error range. In adults with CHF, the mean
      observed/predicted ratio [ratio(Obs/Pred)] for oral clearance (CL/F) without
      reductions in organ blood flows was outside the 2-fold error range, i.e. 0.34 (95
      % confidence interval [CI] 0.31-0.37), with use of both models. The mean CL/F
      ratio(Obs/Pred) values after incorporation of reduced organ blood flows were 1.0
      (95 % CI 0.92-1.08) and 0.95 (95 % CI 0.88-1.03) with use of models 1 and 2,
      respectively. The mean ratio(Obs/Pred) values for the pharmacokinetic parameters
      were not improved after incorporation of reduced blood flows in paediatric
      patients, except in those above 17 years of age, who were categorized according
      to the New York Heart Association classification of CHF, where the CL/F
      ratio(Obs/Pred) values in two patients were closer to unity. CONCLUSION: There
      was a strong connection between a decrease in hepatic clearance of carvedilol and
      an increase in the severity of CHF, especially in adults and in paediatric
      patients above 17 years of age. The incorporated reductions in hepatic and renal
      blood flows occurring in moderate and severe CHF patients resulted in improved
      predictions of carvedilol exposure. The developed models can be extended to
      predict exposures of drugs with high hepatic extraction in the CHF population.

PMID- 25773480
TI  - A Compartmental Analysis for Morphine and Its Metabolites in Young Children After
      a Single Oral Dose.
AB  - BACKGROUND AND OBJECTIVES: Currently, the majority of the surgical procedures
      performed in paediatric hospitals are done on a day care basis, with post
      operative pain being managed by caregivers at home. Pain after discharge of these
      post-operative children has historically been managed with oral codeine in
      combination with paracetamol (acetaminophen). Codeine is an opioid, which elicits
      its analgesic effects via metabolism to morphine and codeine-6-glucuronide. Oral
      morphine is a feasible alternative for outpatient analgesia; however, the
      pharmacokinetics of morphine after oral administration have been previously
      described only sparsely, and there is little information in healthy children.
      METHODS: The clinical trial included 40 children from 2 to 6 years of age, with
      an American Society of Anaesthesiologists physical status classification of 1 or
      2, who were undergoing surgical procedures requiring opioid analgesia. Morphine
      was orally administered prior to surgery in one of three doses: 0.1 mg/kg, 0.2
      mg/kg and 0.3 mg/kg. Blood samples were collected for plasma morphine, morphine-3
      glucuronide (M3G) and morphine-6-glucuronide (M6G) concentrations at 30, 60, 90,
      120, 180 and 240 min after administration. All analyses were performed with the
      non-linear mixed-effect modelling software NONMEM version 7.2, using the first
      order conditional estimation (FOCE) method. RESULTS: A pharmacokinetic model was
      developed to simultaneously describe the plasma profiles of morphine and its
      metabolites M3G and M6G after a single dose of oral morphine in young children (2
      6 years of age). The disposition of morphine, M3G and M6G in plasma was best
      described by a one-compartment model. M3G and M6G metabolite formation was best
      described by a delay transit compartment, indicating a delay in the appearance of
      these two major metabolites. CONCLUSION: This model provides a foundation on
      which to further evaluate the use of oral morphine and its safety in young
      children. Longer follow-up time for morphine oral doses and incorporation of
      other important covariates, such as phenotype, will add value and will help
      overcome the limitations of the presented population pharmacokinetic analysis.

PMID- 25773481
TI  - Tools of the trade: investigations into design strategies of small molecules to
      target components in Alzheimer's disease.
AB  - The growing prevalence of Alzheimer's disease (AD) has warranted the development
      of effective therapeutic methods. Current available drugs for AD (i.e.,
      acetylcholinesterase (AChE) inhibitors and N-methyl-D-aspartate (NMDA) receptor
      antagonists) have only offered brief symptomatic relief. Considering that the
      numbers affected by AD are projected to substantially rise, long-term strategies
      are urgently needed. The multiple series of small molecules to combat AD have
      been expanded, with current methods taking aim at factors, such as misfolded
      protein accumulation, metal ion dyshomeostasis, and oxidative stress. This
      concept article focuses on describing the design of compounds to target various
      components of AD and underlining recent advances that have been made. 

PMID- 25773482
TI  - BK Virus Nephropathy in Heart Transplant Recipients.
AB  - Polyomavirus-associated nephropathy (PVAN) has become an important cause of
      kidney failure in kidney transplant recipients. PVAN is reported to affect 1% to
      7% of kidney transplant recipients, leading to premature transplant loss in
      approximately 30% to 50% of diagnosed cases. PVAN occurring in the native kidneys
      of solid-organ transplant recipients other than kidney only recently has been
      noted. We report 2 cases of PVAN in heart transplant recipients, which brings the
      total of reported cases to 7. We briefly review the literature on the
      hypothesized causes of PVAN in kidney transplant recipients and comment on
      whether these same mechanisms also may cause PVAN in other solid-organ transplant
      recipients. PVAN should be considered in the differential diagnosis when
      evaluating worsening kidney function. BK viremia surveillance studies of
      nonkidney solid-organ recipients should be conducted to provide data to assist
      the transplantation community in deciding whether regular monitoring of nonkidney
      transplant recipients for BK viremia is indicated. 

PMID- 25773484
TI  - Implementation of nephrology subspecialty curricular milestones.
AB  - Beginning in the 2014-2015 training year, the US Accreditation Council for
      Graduate Medical Education (ACGME) required that nephrology Clinical Competency
      Committees assess fellows' progress toward 23 subcompetency "context nonspecific"
      internal medicine subspecialty milestones. Fellows' advancement toward the "ready
      for unsupervised practice" target milestone now is tracked in each of the 6
      competencies: Patient Care, Medical Knowledge, Professionalism, Interpersonal
      Communication Skills, Practice-Based Learning and Improvement, and Systems-Based
      Practice. Nephrology program directors and subspecialty societies must define
      nephrology-specific "curricular milestones," mapped to the nonspecific ACGME
      milestones. Although the ACGME goal is to produce data that can discriminate
      between successful and underperforming training programs, the approach is at risk
      to produce biased, inaccurate, and unhelpful information. We map the ACGME
      internal medicine subspecialty milestones to our previously published nephrology
      specific milestone schema and describe entrustable professional activities and
      other objective assessment tools that inform milestone decisions. Mapping our
      schema onto the ACGME subspecialty milestone reporting form allows comparison
      with the ACGME subspecialty milestones and the curricular milestones developed by
      the American Society of Nephrology Program Directors. Clinical Competency
      Committees may easily adapt and directly translate milestone decisions reached
      using our schema onto the ACGME internal medicine subspecialty competency
      milestone-reporting format. 

PMID- 25773483
TI  - Kidney Failure and ESRD in the Atherosclerosis Risk in Communities (ARIC) Study:
      Comparing Ascertainment of Treated and Untreated Kidney Failure in a Cohort
      Study.
AB  - BACKGROUND: Linkage to the US Renal Data System (USRDS) registry commonly is used
      to identify end-stage renal disease (ESRD) cases, or kidney failure treated with
      dialysis or transplantation, but it underestimates the total burden of kidney
      failure. This study validates a kidney failure definition that includes both
      kidney failure treated and not treated by dialysis or transplantation. It
      compares kidney failure risk factors and outcomes using this broader definition
      with USRDS-identified ESRD risk factors and outcomes. STUDY DESIGN: Diagnostic
      test study with stratified random sampling of hospitalizations for chart review.
      SETTING & PARTICIPANTS: Atherosclerosis Risk in Communities Study (n=11,530;
      chart review, n=546). INDEX TEST: USRDS-identified ESRD; treated or untreated
      kidney failure defined by USRDS-identified ESRD or International Classification
      of Diseases, Ninth or Tenth Revision, Clinical Modification (ICD-9-CM/ICD-10-CM)
      code for hospitalization or death. REFERENCE TEST: For ESRD, determination of
      permanent dialysis therapy or transplantation; for kidney failure, determination
      of permanent dialysis therapy, transplantation, or estimated glomerular
      filtration rate < 15 mL/min/1.73 m(2). RESULTS: During 13 years' median follow
      up, 508 kidney failure cases were identified, including 173 (34.1%) from the
      USRDS registry. ESRD and kidney failure incidence were 1.23 and 3.66 cases per
      1,000 person-years in the overall population and 1.35 and 6.59 cases per 1,000
      person-years among participants older than 70 years, respectively. Other risk
      factor associations were similar between ESRD and kidney failure, except diabetes
      and albuminuria, which were stronger for ESRD. Survivals at 1 and 5 years were
      74.0% and 24.0% for ESRD and 59.8% and 31.6% for kidney failure, respectively.
      Sensitivity and specificity were 88.0% and 97.3% comparing the kidney failure ICD
      9-CM/ICD-10-CM code algorithm to chart review; for USRDS-identified ESRD,
      sensitivity and specificity were 94.9% and 100.0%. LIMITATIONS: Some medical
      charts were incomplete. CONCLUSIONS: A kidney failure definition including
      treated and untreated disease identifies more cases than linkage to the USRDS
      registry alone, particularly among older adults. Future studies might consider
      reporting both USRDS-identified ESRD and a more inclusive kidney failure
      definition.

PMID- 25773486
TI  - Preoperative localization of hyperfunctioning parathyroid glands with 4D-CT.
AB  - Primary hyperparathyroidism (pHPT) is almost exclusively the result of a solitary
      parathyroid adenoma. In most cases, the affected gland can be surgically removed,
      but precise preoperative imaging is essential for adenoma localization prior to
      surgical intervention. In this study, we evaluated the diagnostic value of four
      dimensional computed tomography (4D-CT) as a preoperative imaging tool in
      relation to the localization of pathologic parathyroid glands in patients with
      pHPT and negative sestamibi scans. This study included 43 consecutive patients
      with pHPT referred for parathyroidectomy at the Department of Head and Neck
      Surgery of Copenhagen University Hospital Rigshospitalet in 2011 and 2012. All
      patients had a 4D-CT performed prior to parathyroidectomy. CT localization of the
      suspected adenoma was correlated to the actual surgical findings and subsequent
      histological diagnosis was also available as references for the accuracy of this
      imaging tool. Hyperfunctioning parathyroid glands were found in 40 patients. 4D
      CT identified 32 solitary hyperfunctioning parathyroid glands located on the
      correct side of the neck (PPV 76 %) and 21 located within the correct quadrant
      (PPV 49 %). Unilateral resection was performed in 72 % of patients due to the
      localization findings of preoperative imaging. 4D-CT can, therefore, be
      considered an effective method for the preoperative localization of parathyroid
      adenomas and is an important tool in surgical intervention for patients referred
      to parathyroidectomy.

PMID- 25773485
TI  - Filtration markers as predictors of ESRD and mortality in Southwestern American
      Indians with type 2 diabetes.
AB  - BACKGROUND: A growing number of serum filtration markers are associated with
      mortality and end-stage renal disease (ESRD) in adults. Whether beta-trace
      protein (BTP) and beta2-microglobulin (B2M) are associated with these outcomes in
      adults with type 2 diabetes is not known. STUDY DESIGN: Longitudinal cohort
      study. SETTING & PARTICIPANTS: 250 Pima Indians with type 2 diabetes (69% women;
      mean age, 42 years; mean diabetes duration, 11 years). PREDICTORS: Serum BTP,
      B2M, and glomerular filtration rate measured by iothalamate clearance (mGFR) or
      estimated using creatinine (eGFRcr) or cystatin C level (eGFRcys). OUTCOMES &
      MEASUREMENTS: Incident ESRD and all-cause mortality through December 2013. HRs
      were reported per interquartile range decrease of the inverse of BTP and B2M
      (1/BTP and 1/B2M) using Cox regression. Improvement in risk prediction with the
      addition of BTP or B2M level to established markers (eGFRcys with mGFR or eGFRcr)
      was evaluated using C statistics, continuous net reclassification improvement,
      and relative integrated discrimination improvement (RIDI). RESULTS: During a
      median follow-up of 14 years, 69 participants developed ESRD and 95 died. Both
      novel markers were associated with ESRD in multivariable models. BTP level
      remained statistically significant after further adjustment for mGFR (1/BTP, 1.53
      [95% CI, 1.01-2.30]; 1/B2M, 1.54 [95% CI, 0.98-2.42]). B2M level was associated
      with mortality in multivariable models and after further adjustment for mGFR (HR,
      2.12; 95% CI, 1.38-3.26). The addition of B2M level to established markers
      increased the C statistic for mortality but only weakly when assessed by either
      continuous net reclassification improvement or RIDI; none was improved for ESRD
      by the addition of these markers. LIMITATIONS: Small sample size, single
      measurements of markers. CONCLUSIONS: In Pima Indians with type 2 diabetes, BTP
      and, to a lesser extent, B2M levels were associated with ESRD. B2M level was
      associated with mortality after adjustment for traditional risk factors and
      established filtration markers. Further studies are warranted to confirm whether
      inclusion of B2M level in a multimarker approach leads to improved risk
      prediction for mortality in this population.

PMID- 25773487
TI  - Radiation therapy for nasal vestibule squamous cell carcinoma: a 40-year
      experience.
AB  - We evaluated the treatment of squamous cell carcinoma (SCC) of the nasal
      vestibule. Eighty-six patients were treated with radiotherapy (RT) and 13
      patients received surgery and RT. The mean follow-up was: 9.7 years (range 4
      months-35.9 years). The 5- and 10-year outcomes were: local control (LC), 88 and
      82 %; local-regional control (LRC), 78 and 73 %; freedom from distant metastases
      (FFDM), 96 and 96 %; cause-specific survival (CSS), 91 and 86 %; and overall
      survival, 75 and 51 %. The 5- and 10-year LC rates for patients treated with RT
      were 94 and 89 % overall. A multivariate analysis was performed. Tumor size
      predicted LC, LRC, OS, and CSS. Overall stage predicted LRC. RT cures most
      patients with T1-T2 and favorable T4 SCCs with acceptable toxicity. RT and
      surgery result in improved likelihood of cure for patients with advanced T4
      lesions.

PMID- 25773488
TI  - The malaria co-infection challenge: An investigation into the antimicrobial
      activity of selected Guinean medicinal plants.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: In sub-Saharan Africa, concomitant occurrence of
      malaria and invasive infections with micro-organisms such as Gram-positive
      Staphylococcus aureus, Gram-negative Escherichia coli and yeasts or fungi such as
      Candida albicans and Aspergillus fumigatus is common. Non-tuberculous
      mycobacteriosis caused by Mycobacterium chelonae has been recognized as a
      pulmonary pathogen with increasing frequency without effective therapy. Although
      less important, the high incidence of Trichophyton rubrum infections along with
      its ability to evade host defense mechanisms, accounts for the high prevalence of
      infections with this dermatophyte. Considering the treatment cost of both malaria
      and microbial infections, along with the level of poverty, most affected African
      countries are unable to cope with the burden of these diseases. In sub-Saharan
      Africa, many plant species are widely used in the treatment of these diseases
      which are traditionally diagnosed through the common symptom of fever. Therefore
      it is of interest to evaluate the antimicrobial activities of medicinal plants
      reported for their use against malaria/fever. MATERIALS AND METHODS: Based on an
      ethnobotanical survey, 34 Guinean plant species widely used in the traditional
      treatment of fever and/or malaria have been collected and evaluated for their
      antimicrobial activities. Plants extracts were tested against Candida albicans,
      Trichophyton rubrum, Aspergillus fumigatus, Mycobacterium chelonae,
      Staphylococcus aureus and Escherichia coli. RESULTS: The most interesting
      activities against Candida albicans were obtained for the polar extracts of
      Pseudospondias microcarpa and Ximenia americana with IC50 values of 6.99 and 8.12
      ug/ml, respectively. The most pronounced activity against Trichophyton rubrum was
      obtained for the ethanol extract of Terminalia macroptera (IC50 5.59 ug/ml). Only
      7 of the 51 tested extracts were active against Staphylococcus aureus. From
      these, the methanolic extracts of the leaves and stem bark of Alchornea
      cordifolia were the most active with IC50 values of 2.81 and 7.47 ug/ml,
      respectively. Only Terminalia albida and Lawsonia inermis showed activity against
      Mycobacterium chelonae. None of the tested extracts was active against
      Escherichia coli. CONCLUSION: A number of traditional Guinean plant species used
      against malaria/fever showed, in addition to their antiplasmodial properties and
      antimicrobial activity. The fact that some plant species are involved in the
      traditional treatment of malaria/fever without any antiplasmodial evidence may be
      justified by their antimicrobial activities.

PMID- 25773489
TI  - Medicinal plants used as excipients in the history in Ghanaian herbal medicine.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: The present study was carried out to investigate
      the traditional use, pharmacology and active compounds of four plants commonly
      used as excipients in herbal medicine in Ghana. MATERIALS AND METHODS: A
      comprehensive literature search was conducted to gain knowledge about the
      traditional use, pharmacology and active compounds of the four plant excipients.
      The broth dilution antibacterial assay and the DPPH radical scavenging
      antioxidant assay were used to evaluate the antibacterial and antioxidant
      activity of the plants, respectively. Ethanol, warm water and cold water extracts
      were prepared from the dried seeds/fruits of Aframomum melegueta, Piper
      guineense, Xylopia aethiopica and Monodora myristica, and tested in the assays.
      RESULTS: A. melegueta and P. guineense seemed to act as pharmacoenhancers, since
      they have been shown to inhibit specific CYP-enzymes. A. melegueta could act as
      an antioxidant to preserve herbal preparations. None of the plant excipients had
      antibacterial activity against the bacteria tested in this study. Compounds with
      an aromatic or pungent smell had been identified in all the plant excipients. An
      explanation for the use of the plants as excipients could rely on their taste
      properties. CONCLUSION: The present study suggests that there may be more than
      one simple explanation for the use of these four plants as excipients. Plausible
      explanations have been proven to be: (1) a way to increase the effect of the
      medicine, (2) a way to make the medicine more palatable or (3) a way to preserve
      the activity of the medicinal preparation over time.

PMID- 25773490
TI  - Activity of medicinal plants from Ghana against the parasitic gut protist
      Blastocystis.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: The plants tested in this study were examples of
      plants historically used to treat or alleviate several types of stomach disorders
      manifested by e.g. stomachache, diarrhoea or dysentery. These plants have been
      consumed typically as a decoction, sometimes mixed with other flavourings. The
      aim of this study was to evaluate the anti-Blastocystis activity of 24 plant
      parts from 21 medicinal plants from Ghana. MATERIALS AND METHODS: The medicinal
      plants were collected in the Greater Accra region of Ghana. Every plant part was
      tested in three different extracts; an ethanolic, a warm, and a cold water
      extract, at a final concentration of 1 mg/mL for the initial screening, and in a
      range from 0.0156 to 1mg/mL for determination of inhibitory concentrations. The
      obligate anaerobic parasitic gut protist Blastocystis (subtype 4) was used as a
      48 h old subcultivated isolate in the final concentration of 10(6) cells/mL.
      Plant extracts inoculated with Blastocystis were incubated at 37  degrees C for
      24 h and 48 h. Both MIC minimum inhibitory concentration (MIC90) assays and
      minimal lethal concentration (MLC) assays were performed after 24 h and 48 h. The
      half maximal inhibitory concentration (IC50) was derived after 24 h and 48 h.
      Antimicrobial activity was tested against two Gram-positive and two Gram-negative
      bacteria for all 24 plant parts at a final concentration of 1mg/mL. RESULTS:
      Screening of the 24 different plant parts showed significant anti-Blastocystis
      activity of six of the ethanolic extracts: Mallotus oppositifolius, IC50, 24 h
      27.8 ug/mL; Vemonia colorata, IC50, 24 h 117.9 ug/mL; Zanthoxylum zanthoxyloides,
      cortex IC50, 24 h 255.6 ug/mL; Clausena anisata, IC50, 24 h 314.0 ug/mL; Z.
      zanthoxyloides, radix IC50, 24 h 335.7 ug/mL and Eythrina senegalensis, IC50, 24
      h 527.6 ug/mL. The reference anti-protozoal agent metronidazole (MTZ) had an
      IC50, 24 h of 7.6 ug/mL. Only C. anisata showed antimicrobial activity at a
      concentration of 800 ug/mL. CONCLUSION: Six ethanolic plant extracts showed
      significant anti-parasitic activity against Blastocystis. M. oppositifolius
      showed nearly as good activity as the reference anti-protozoal drug MTZ.
      Historically, the active plants found in this study have been used against
      dysentery, diarrhoea or other stomach disorders. Nowadays they are not used
      specifically for dysentery, but they are being used as medicinal plants against
      various stomach disorders.

PMID- 25773491
TI  - Incorporating founder virus information in vaccine field trials.
AB  - Vaccine clinical trials with active surveillance for infection often use the time
      to infection as the primary endpoint. A common method of analysis for such trials
      is to compare the times to infection between the vaccine and placebo groups using
      a Cox regression model. With new technology, we can sometimes additionally record
      the precise number of virions that cause infection rather than just the indicator
      that infection occurred. In this article, we develop a unified approach for
      vaccine trials that couples the time to infection with the number of infecting or
      founder viruses. We assume that the instantaneous risk of a potentially
      infectious exposure for individuals in the placebo and vaccine groups follows the
      same proportional intensity model. Following exposure, the number of founder
      viruses X* is assumed to be generated from some distribution on 0,1,..., which is
      allowed to be different for the two groups. Exposures that result in X*=0 are
      unobservable. We denote the placebo and vaccine means of X* by MU and MUDelta so
      that 1-Delta measures the proportion reduction in the mean number of infecting
      virions due to vaccination per exposure. We develop different semi-parametric
      methods of estimating Delta. We allow the distribution of X* to be Poisson or
      unspecified, and discuss how to incorporate covariates that impact the time to
      exposure and/or X*. Interestingly Delta, which is a ratio of untruncated means,
      can be reliably estimated using truncated data (X*>0), even if the placebo and
      vaccine distributions of X* are completely unspecified. Simulations of vaccine
      clinical trials show that the method can reliably recover Delta in realistic
      settings. We apply our methods to an HIV vaccine trial conducted in injecting
      drug users. 

PMID- 25773492
TI  - The relationship between the boron dipyrromethene (BODIPY) structure and the
      effectiveness of homogeneous and heterogeneous solar hydrogen-generating systems
      as well as DSSCs.
AB  - A series of boron dipyrromethene (BODIPY) dyes (B1-B5) having H atoms at 2,6
      positions or heavy-atom I at 2-/2,6-positions, and an ortho- or a para-COOH
      substituted phenyl moiety at the 8-position on the BODIPY core were synthesized
      and characterized. These organic dyes were applied for investigating the
      relationship between the BODIPY structure and the effectiveness of homogeneous
      and heterogeneous visible-light-driven hydrogen production as well as dye
      sensitized solar cells (DSSCs). For the homogeneous photocatalytic hydrogen
      production systems with a cobaloxime catalyst, the efficiency of hydrogen
      production could be tuned by substituting with heavy atoms and varying carboxyl
      group orientations of BODIPYs. As a result, B5 containing two I atoms and an
      ortho-COOH anchoring group was the most active one (TONs = 197). The activity of
      hydrogen generation followed the order B5 > B3 > B2 > B1 = B4 = 0. An interesting
      "ortho-position effect" was observed in the present homogeneous systems, i.e.,
      substitution groups were located at the ortho-position and higher hydrogen
      production activities were obtained. For the heterogeneous hydrogen production
      systems with a platinized TiO2 catalyst, the effectiveness of hydrogen evolution
      was highly influenced by the intersystem crossing efficiency, molar absorptivity
      and positions of the anchoring group of dyes. Thus, B3 having two core iodine
      atoms and a para-COOH group with TONs of 70 excelled other BODIPYs and the TONs
      of hydrogen generation showed the trend of B3 > B5 > B2 > B1 = B4 = 0. The
      results demonstrate that the present photocatalytic H2 production proceeds with
      higher efficiency and stability in the homogeneity than in the heterogeneity. In
      the case of DSSCs, the overall cell performance of BODIPY chromophores was highly
      dependent on both the absence or the presence of iodine atoms on the BODIPY core
      and -COOH anchoring positions. The B1-TiO2 system showed the best cell
      performance, because the most effective surface binding mode is allowed with this
      structure. This is also in contrast with the case of dye-sensitized solar H2
      generation, in which B3 was the most efficient chromophore. The differences
      between dye-sensitized hydrogen-generating systems and DSSCs may be due to rates
      of electron transfer and the dye aggregation tendency.

PMID- 25773494
TI  - Homoleptic low-valent polyazides of group 14 elements.
AB  - First examples of coordinatively unsaturated, homoleptic azido complexes of low
      valent group 14 elements are reported. A simple strategy uses low-valent
      precursors, ionic azide transfer reagents and bulky cations to obtain salt-like
      compounds containing E(N3)3(-) of Ge(II)/Sn(II) which are fully characterised,
      including XRD. Remarkably, these compounds are kinetically stable at r.t. and
      isolable in sub-gram quantities.

PMID- 25773493
TI  - Clinical outcomes in 66 patients with advanced gastric cancer treated in phase I
      trials: the NCCHE experience.
AB  - BACKGROUND: Although patients with advanced gastric cancer (AGC) have a poor
      prognosis when conventional therapies fail, they are often candidates for phase I
      trials. However, there is no detailed report on clinical outcomes of patients
      with AGC treated in phase I trials. METHODS: We retrospectively reviewed the
      medical records of 66 consecutive patients with AGC enrolled in phase I trials
      between March 2008 and July 2014 at our institution in Japan. RESULTS: Median age
      was 66 years (range, 28-78 years) and median number of previous lines of
      conventional chemotherapy was 3 (range, 1-6). Five (8.6 %) and seven (12 %)
      patients showed objective response and stable disease >3 months, respectively.
      Although the time to treatment failure (TTF) of the best phase I treatment was
      shorter than that of the last line of conventional chemotherapy (median 1.5 vs.
      2.3 months; P = 0.002), TTF of the best phase I treatment was longer than that of
      the last line of treatment in 21 patients (32 %). Severe adverse events and grade
      3 or higher toxicities were reported in eight (12 %) and 13 patients (20 %),
      respectively. No treatment-related death was observed. Median survival time from
      the start of phase I treatment was 7.5 months, and four deaths (6 %) within 30
      days after last administration were observed. CONCLUSION: Phase I trials of
      patients with AGC was acceptably feasible with some efficacy signal. Our results
      suggest that phase I trials might be one treatment option for patients with AGC
      when conventional therapies fail.

PMID- 25773495
TI  - Historical classics: Editorial.

PMID- 25773496
TI  - GSK256073 acutely regulates NEFA levels via HCA2 agonism but does not achieve
      durable glycaemic control in type 2 diabetes. A randomised trial.
AB  - This study investigated safety and efficacy of GSK256073, an in vitro potent,
      selective GPR109A agonist, for treatment of subjects with type 2 diabetes
      mellitus (Type 2 DM) poorly controlled with metformin alone. Patients with Type 2
      DM (n=94) were enroled into this randomised, double-blind (sponsor unblinded),
      placebo-controlled, parallel group trial. Participants received placebo for two
      weeks before being randomised (2:2:2:2:1:1) to receive doses of GSK256073 5mg
      twice-daily (BID), 10mg once-daily (QD), 25mg BID, 50mg QD or placebo BID or QD
      in addition to their current metformin treatment. The primary efficacy endpoint
      was change from baseline in glycosylated haemoglobin (HbA1c) at week 12. The
      safety profile of GSK256073 did not significantly differ from that of placebo.
      Decreases from baseline in HbA1c were observed in all treatment groups but were
      not statistically significant compared to placebo; at week 12 a maximum decrease
      of 0.30% from placebo was reached in the GSK256073 50mg QD group. On day 2,
      GSK256073 significantly decreased non-esterified fatty acid (NEFA) (0-12h)
      concentrations but pharmacological activity was lost (5mg BID, 10mg QD, 25mg BID)
      or reduced (50mg QD) at week 6. Drug exposure demonstrated 2-fold accumulation
      over 6 weeks. The primary efficacy objective of the study was not met. GSK256073
      did not improve HbA1c concentrations at week 12. Despite sustained drug exposure,
      the ability of the HCA2 agonist to suppress plasma NEFA concentrations waned over
      time and targeted effects on glucose oxidation and insulin sensitivity subsided.

PMID- 25773497
TI  - Discovery and characterization of GSK256073, a non-flushing hydroxy-carboxylic
      acid receptor 2 (HCA2) agonist.
AB  - Niacin has been used for many years in the treatment of dyslipidemia due to its
      ability to decrease serum levels of triglycerides and low-density lipoprotein
      cholesterol and to increase levels of high density lipoprotein cholesterol.
      However, niacin causes severe flushing resulting in poor patient compliance. The
      discovery of hydroxy-carboxylic acid receptor 2 (HCA2) as a high affinity
      receptor for niacin has opened avenues to investigate the mechanism of action of
      niacin, and to potentially discover agonists which maintain the antilipolytic
      effects of niacin accessed by a decrease in circulating non-esterified fatty
      acids (NEFA) and thereby perhaps the lipid/lipoprotein effects, but avoid the
      flushing effects. Here we describe the strategy we implemented to identify such
      compounds. This approach resulted in the discovery of GSK256073, a highly potent
      HCA2 agonist, which produced similar NEFA lowering effects to niacin in
      preclinical models (rat and guinea pig). A guinea pig model was used to predict
      flushing, via an increase in ear temperature, and GSK256073 was found to have a
      minimal effect in this model. These preclinical models appeared to be predictive
      of human response, since in a first-time-in-human study, GSK256073 displayed long
      lasting NEFA and triglyceride lowering effects in healthy male subjects, which
      were not associated with flushing. GSK256073 can be used as a pharmacological
      tool to better understand the role of HCA2 in lipid metabolism.

PMID- 25773498
TI  - Magnesium lithospermate B and rosmarinic acid, two compounds present in Salvia
      miltiorrhiza, have potent antiviral activity against enterovirus 71 infections.
AB  - The aim of this study was to identify the active ingredients responsible for the
      anti-EV71 activity produced by Salvia miltiorrhiza extracts. A pGS-EV71 IRES
      based bicistronic reporter assay platform was used for rapid analysis of
      compounds that could specifically inhibit EV71 viral IRES-mediated translation.
      The analysis identified 2 caffeic acid derivatives, magnesium lithospermate B
      (MLB) and rosmarinic acid (RA), which suppressed EV71 IRES-mediated translation
      at concentrations of 30MUg/ml. We also found that MLB and RA inhibited EV71
      infection when they were added to RD cells during the viral absorption stage. MLB
      had a low IC50 value of 0.09mM and a high TI value of 10.52. In contrast, RA had
      an IC50 value of 0.50mM with a TI value of 2.97. MLB and RA (100ug/ml) also
      reduced EV71 viral particle production and significantly decreased VP1 protein
      production. We propose that these two derivatives inhibit EV71 viral entry into
      cells and viral IRES activity, thereby reducing viral particle production and
      viral RNA expression and blocking viral VP1 protein translation. This study
      provides useful information for the development of anti-EV71 assays and reagents
      by demonstrating a convenient EV71 IRES-based bicistronic assay platform to
      screen for anti-EV71 IRES activity, and also reports 2 compounds, MLB and RA,
      which are responsible for the anti-EV71 activity of S. miltiorrhiza.

PMID- 25773499
TI  - Center-Level Experience and Kidney Transplant Outcomes in HIV-Infected
      Recipients.
AB  - Excellent outcomes among HIV+ kidney transplant (KT) recipients have been
      reported by the NIH consortium, but it is unclear if experience with HIV+ KT is
      required to achieve these outcomes. We studied associations between experience
      measures and outcomes in 499 HIV+ recipients (SRTR data 2004-2011). Experience
      measures examined included: (1) center-level participation in the NIH consortium;
      (2) KT experiential learning curve; and (3) transplant era (2004-2007 vs. 2008
      2011). There was no difference in outcomes among centers early in their
      experience (first 5 HIV+ KT) compared to centers having performed >6 HIV+ KT (GS
      adjusted hazard ratio [aHR]: 1.05, 95% CI: 0.68-1.61, p = 0.82; PS aHR: 0.93; 95%
      CI: 0.56-1.53, p = 0.76), and participation in the NIH-study was not associated
      with any better outcomes (GS aHR: 1.08, 95% CI: 0.71-1.65, p = 0.71; PS aHR:
      1.13; 95% CI: 0.68-1.89, p = 0.63). Transplant era was strongly associated with
      outcomes; HIV+ KTs performed in 2008-2011 had 38% lower risk of graft loss (aHR:
      0.62; 95% CI: 0.42-0.92, p = 0.02) and 41% lower risk of death (aHR: 0.59; 95%
      CI: 0.39-0.90, p = 0.01) than that in 2004-2007. Outcomes after HIV+ KT have
      improved over time, but center-level experience or consortium participation is
      not necessary to achieve excellent outcomes, supporting continued expansion of
      HIV+ KT in the US.

PMID- 25773501
TI  - Colo-colonic anastomosis in a continuous-flow left ventricular assist device
      patient.
AB  - Noncardiac operations are being increasingly performed on patients with left
      ventricular assist devices (LVADs). However, little is known on the impact of
      continuous-flow LVADs on the vascular supply of the colon for anastomoses. In
      this case, a 67-year-old male supported on an LVAD underwent four successful
      noncardiac operations including two intestinal anastomoses; left colon and small
      bowel anastomosis. To the best of our knowledge, no existing literature has
      reported successful colonic anastomosis on a continuous-flow LVAD. This case
      illustrates the plausibility of performing colonic anastomoses with appropriately
      selected patients supported on an LVAD. A 67-year-old male with congestive heart
      failure underwent LVAD placement for decompensated heart failure while awaiting
      orthotopic transplantation. During his recovery, he developed a stage IV sacral
      decubitus ulcer which required a sigmoid loop colostomy placement and a
      rotational flap. Subsequent stoma closure with partial sigmoid colectomy and
      stapled anastomosis was performed, and healed without evidence of anastomotic
      leak. This case illustrates the potential for colonic anastomoses for patients on
      continuous-flow LVAD support. Although oxygenation is known to be an important
      aspect of healing, this patient's outcome suggests that intestinal anastomoses
      can be performed on the induced pulseless environment of an LVAD. Further studies
      will be needed to further elucidate the success of longer segment resections and
      appropriate surgical candidates.

PMID- 25773502
TI  - The sum of defined daily doses does not represent the potency of an
      antihypertensive drug regimen.

PMID- 25773503
TI  - Comparison between minimal right vertical infra-axillary thoracotomy and standard
      median sternotomy for repair of atrial septal defects.
AB  - BACKGROUND: The minimal right vertical infra-axillary thoracotomy could be a safe
      and cosmetic alternative to standard median sternotomy. This study reviews our
      results and experience with a minimal right vertical infra-axillary thoracotomy
      technique for the repair of atrial septal defects compared with standard median
      sternotomy. METHODS: The study was designed as a retrospective, observational,
      and case-controlled study. Between May 2007 and November 2012, 26 patients
      underwent atrial septal defect closure with standard median sternotomy (Group 1).
      This group was compared with 21 patients who underwent repair of atrial septal
      defects using minimal right vertical infra-axillary thoracotomy (Group 2).
      Quantitative data were given as mean +/- standard deviation, and qualitative
      values were expressed as percentages. In the comparison of the normal variables
      between the two groups, we used independent sample t test, and in the comparison
      of categorical variables between groups, Chi-square test was used. RESULTS: The
      mean length of incision was significantly shorter in Group 2 than in Group 1 (p =
      0.03). The time it took to establish cardiopulmonary bypass was longer in Group 2
      (p = 0.04). There were no statistically significant differences in
      cardiopulmonary bypass time (p = 0.11), aortic cross-clamp time (p = 0.10), and
      total operation time (p = 0.10) between the two groups. Group 2 had less chest
      tube drainage (p = 0.04), less blood transfusion (p = 0.02), and shorter
      postoperative mechanical ventilation time (p = 0.09) than Group 1. CONCLUSION:
      Minimal right vertical infra-axillary thoracotomy can be performed with favorable
      cosmetic and clinical results for atrial septal defects closure. Infra-axillary
      thoracotomy provides a good alternative to standard median sternotomy for
      patients with atrial septal defects.

PMID- 25773504
TI  - Application of the LMA-SupremeTM and i-gelTM laryngeal masks during pelvic
      operations in adults.
AB  - OBJECTIVE: The aim of this study was to evaluate the practical application and
      safety of the i-gel and LMA-Supreme laryngeal masks for airway management during
      pelvic operations in adults. METHODS: Ninety patients undergoing general
      anesthesia for elective pelvic operations (ASA Grades I-II) were randomly divided
      into two groups, the i-gel group and the Supreme group. The laryngeal mask was
      inserted after induction, and the relevant examination grading indexes were
      recorded. RESULTS: The Supreme group required less time for laryngeal mask
      insertion and gastric tube indwelling time. Gastric tube indwelling was easier,
      compared with those in the i-gel group (p = 0.03), but the i-gel group had fewer
      complications (p = 0.03). There were no significant differences in the degree of
      difficulty in insertion, airway sealing pressure, PETCO2, Ppeak, and laryngeal
      mask alignment accuracy between the two groups (p > 0.05). There was no
      statistically significant difference in fibrobronchoscopy grading between the two
      groups (p > 0.05). CONCLUSION: The i-gel and LMA-Supreme laryngeal masks are safe
      and effective for airway management in patients during pelvic operations.

PMID- 25773500
TI  - Genetics and brain morphology.
AB  - A wealth of empirical evidence is accumulating on the genetic mediation of brain
      structure phenotypes. This comes from twin studies that assess heritability and
      genetic covariance between traits, candidate gene associations, and genome-wide
      association studies (GWAS) that can identify specific genetic variants. Here we
      review the major findings from each of these approaches and consider how they
      inform on the genetic architecture of brain structure. The findings from twin
      studies show there is a strong genetic influence (heritability) on brain
      structure, and overlap of genetic effects (pleiotropy) between structures, and
      between structure and cognition. However, there is also evidence for genetic
      specificity, with distinct genetic effects across some brain regions. Candidate
      gene associations show little convergence; most have been under powered to detect
      effect sizes of the magnitude now expected. GWAS have identified 19 genetic
      variants for brain structure, though no replicated associations account for more
      than 1% of the variance. Together these studies are revealing new insights into
      the genetic architecture of brain morphology. As the scope of inquiry broadens,
      including measures that capture the complexity of the brain, along with larger
      samples and new analyses, such as genome-wide common trait analysis (GCTA) and
      polygenic scores, which combine variant effects for a phenotype, as well as whole
      genome sequencing, more genetic variants for brain structure will be identified.
      Increasingly, large-scale multi-site studies will facilitate this next wave of
      studies, and promise to enhance our understanding of the etiology of variation in
      brain morphology, as well as brain disorders.

PMID- 25773505
TI  - A dehydrogenative cross-coupling reaction between aromatic aldehydes or ketones
      and dialkyl H-phosphonates for formyl or acylphenylphosphonates.
AB  - A novel DCC reaction between aromatic aldehydes or ketones and H-phosphonates has
      been developed for the synthesis of p-formyl or p-acylphenylphosphonates. The
      synthetic method has excellent para regioselectivities, good yields, and broad
      substrate scopes and is more benign to the environment. The DCC reaction also
      tolerates many functional groups, and results in a series of new p-formyl and p
      acylphenylphosphonates, which should be important building blocks for the
      synthesis of versatile arylphosphonate derivatives. 

PMID- 25773506
TI  - Patient perspectives on centralisation of low volume, highly specialised
      procedures in Sweden.
AB  - This study explores important considerations from a patient perspective in
      decisions regarding centralisation of specialised health care services. The
      analysis is performed in the framework of the Swedish National Board of Health
      and Welfare's ongoing work to evaluate and, if appropriate, centralise low
      volume, highly specialised, health services defined as National Specialised
      Medical Care. In addition to a literature review, a survey directed to members of
      patient associations and semi-structured interviews with patient association
      representatives and health care decision makers were conducted. The results
      showed that from a patient perspective, quality of care in terms of treatment
      outcomes is the most important factor in decisions regarding centralisation of
      low volume, highly specialised health care. The study also indicates that
      additional factors such as continuity of treatment and a well-functioning care
      pathway are highly important for patients. However, some of these factors may be
      dependent on the implementation process and predicting how they will evolve in
      case of centralisation will be difficult. Patient engagement and patient
      association involvement in the centralisation process is likely to be a key
      component in attaining patient focused care and ensuring patient satisfaction
      with the centralisation decisions. 

PMID- 25773507
TI  - Balancing the risks and benefits of dual platelet inhibition.

PMID- 25773508
TI  - Cardiovascular imaging and outcomes--PROMISEs to keep.

PMID- 25773509
TI  - The rejuvenating effect of pregnancy on muscle regeneration.
AB  - Aging is characterized by reduced tissue regenerative capacity attributed to a
      diminished responsiveness of tissue-specific stem cells. With increasing age,
      resident precursor cells in muscle tissues show a markedly impaired propensity to
      proliferate in response to damage. However, exposure to factors present in the
      serum of young mice restores the regenerative capacity of aged precursor cells.
      As pregnancy represents a unique biological model of a partially shared blood
      system between young and old organisms, we hypothesized that pregnancy in aged
      mice would have a rejuvenating effect on the mother. To test this hypothesis, we
      assessed muscle regeneration in response to injury in young and aged pregnant and
      nonpregnant mice. Muscle regeneration in the aged pregnant mice was improved
      relative to that in age-matched nonpregnant mice. The beneficial effect of
      pregnancy was transient, lasting up to 2 months after delivery, and appeared to
      be attributable to activation of satellite cells via the Notch signaling pathway,
      thus supporting the possibility that pregnancy induces activation of aged dormant
      muscle progenitor cells.

PMID- 25773511
TI  - Surfactant-free polyurethane nanocapsules via inverse Pickering miniemulsion.
AB  - We report on a surfactant-free synthesis of Pickering-stabilized submicrometer
      sized capsules in inverse miniemulsion. Functionalized silica nanoparticles are
      able to stabilize water-in-cyclohexane miniemulsions to form stable polyurethane
      shells via interfacial polyaddition. The effect of the type of silica
      functionalization on the stabilizing properties is demonstrated by varying the
      hydrophobicity and, therefore, the contact angle between silica and the two
      liquid phases. Addition of small amounts of salt leads to a reduction of the
      capsule size and to a narrow size distribution. The impermeability of the formed
      capsule shell is proven by encapsulation of an organic fluorescent dye and
      release studies in aqueous environment. In addition, we show the possibility to
      encapsulate large amounts of inorganic salts without negative effects concerning
      the stability of the emulsion, which enables the application for phase-change
      materials. 

PMID- 25773510
TI  - Subjective and objective physical activity patterns after Roux-en Y gastric
      bypass surgery compared with non-operated obese and non-obese control women.
AB  - INTRODUCTION: Previous studies on physical activity after bariatric surgery
      provided inconsistent results. The aim of our study was to comprehensively assess
      physical activity by subjective (questionnaires) and objective (accelerometry)
      measures in women who had undergone Roux-en Y gastric bypass (RYGB) surgery and
      to compare results with those of women displaying grade II or higher obesity and
      of non-obese control women. METHODS: Our cross-sectional case-control study
      included 12 women in each group (RYGB, obese, non-obese). Wrist accelerometry was
      performed over 5 days. Two questionnaires were used to assess women's self
      reported leisure- and work-time and sport-related physical activity. RESULTS:
      Accelerometry indicated a lower physical activity in RYGB women than in non-obese
      women in particular during the weekend (p=0.010), while there was no difference
      between RYGB and obese women (p=0.57). Questionnaires revealed that RYGB women
      self-report a greater leisure- and work-time physical activity than obese women
      and also greater work-related physical activity than non-obese women (all
      p<=0.032). In contrast, sport-related activities were reduced in RYGB as compared
      with non-obese women (p=0.011), while there was no difference between RYGB and
      obese women (p=0.51). Comparison of the obese and non-obese group revealed less
      leisure-time and sport-related activities in the obese women (both p<=0.002).
      DISCUSSION: Despite the preliminary character of our rather small study, data
      suggest a differential physical activity pattern in women who have previously
      undergone RYGB surgery that is characterized by rare sport activities, an
      increased subjective work-related physical activity and objectively reduced
      physical activity during the weekend as compared with non-obese control women.

PMID- 25773512
TI  - Preparation of magnetic core-shell iron oxide@silica@nickel-ethylene glycol
      microspheres for highly efficient sorption of uranium(VI).
AB  - We report a facile approach for the formation of magnetic core-shell iron
      oxide@silica@nickel-ethylene glycol (Fe3O4@SiO2@Ni-L) microspheres. The structure
      and morphology of Fe3O4@SiO2@Ni-L are characterized by X-ray diffraction (XRD),
      scanning electron microscopy (SEM), transmission electron microscopy (TEM) and
      nitrogen sorption isotherm. The composite possesses a high specific surface area
      of 382 m(2) g(-1). The obtained core/shell structure is composed of a
      superparamagnetic core with a strong response to external fields, which are
      recovered readily from aqueous solutions by magnetic separation. When used as the
      adsorbent for uranium(vi) in water, the as-prepared Fe3O4@SiO2@Ni-L multi
      structural microspheres exhibit a high adsorption capacity, which is mainly
      attributed to the large specific surface area and typical mesoporous
      characteristics of Fe3O4@SiO2@Ni-L microspheres. This work provides a promising
      approach for the design and synthesis of multifunctional microspheres, which can
      be used for water treatment, as well as having other potential applications in a
      variety of biomedical fields including drug delivery and biosensors. 

PMID- 25773513
TI  - Congenital microtia in a neonate due to maternal isotretinoin exposure 1 month
      before pregnancy: Case Report.
AB  - Isotretinoin is a drug used for treating severe cystic/nodular acne. Severe
      malformations have been documented in neonates whose mothers had taken
      isotretinoin during pregnancy. Women who became pregnant one cycle after
      completing therapy are believed to be at teratogenic risk not higher than
      baseline. We describe the case of a newborn whose mother had taken the drug for 4
      weeks. The woman then had contraception for 4 weeks (after the drug treatment had
      finished), and became pregnant after that period. The newborn had isolated
      bilateral microtia due to suspected isotretinoin exposure. His mother also had a
      history of urine tract infection in the second week of pregnancy that was treated
      with cephalexin. The parents were not from a consanguineous marriage and had no
      family history of congenital malformations. To reduce the risk, effective
      contraception should be continued in fertile women more than 1 month after
      completing therapy. 

PMID- 25773514
TI  - Lipidomics as an important key for the identification of beer-spoilage bacteria.
AB  - Electrospray ionization-tandem mass spectrometry (ESI-MS/MS) was used for
      characterizing intact plasmalogen phospholipid molecules in beer-spoilage
      bacteria. Identification of intact plasmalogens was carried out using collision
      induced dissociation and the presence of suitable marker molecular species, both
      qualitative and quantitative, was determined in samples containing the anaerobic
      bacteria Megasphaera and Pectinatus. Using selected ion monitoring (SIM), this
      method had a limit of detection at 1 pg for the standard, i.e. 1-(1Z-octadecenyl)
      2-oleoyl-sn-glycero-3-phosphoethanolamine and be linear in the range of four
      orders of magnitude from 2 pg to 20 ng. This technique was applied to intact
      plasmalogen extracts from the samples of contaminated and uncontaminated beer
      without derivatization and resulted in the identification of contamination of
      beer by Megasphaera and Pectinatus bacteria. The limit of detection was about 830
      cells of anaerobic bacteria, i.e. bacteria containing natural cyclopropane
      plasmalogenes (c-p-19:0/15:0), which is the majority plasmalogen located in both
      Megasphaera and Pectinatus. The SIM ESI-MS method has been shown to be useful for
      the analysis of low concentration of plasmalogens in all biological samples,
      which were contaminated with anaerobic bacteria, e.g. juice, not only in beer.
      Significance and impact of the study: Electrospray ionization-tandem mass
      spectrometry (ESI-MS/MS) using collision-induced dissociation was used to
      characterize intact plasmalogen phospholipid molecules in beer-spoilage anaerobic
      bacteria Megasphaera and Pectinatus. Using selected ion monitoring (SIM), this
      method has a detection limit of 1 pg for the standard 1-(1Z-octadecenyl)-2-oleoyl
      sn-glycero-3-phosphoethanolamine and is linear within four orders of magnitude (2
      pg to 20 ng). The limit of detection was about 830 cells of bacteria containing
      natural cyclopropane plasmalogen (c-p-19:0/15:0). SIM ESI-MS method is useful for
      analyzing low concentrations of plasmalogens in biological samples contaminated
      with anaerobic bacteria, e.g. beer or juice.

PMID- 25773516
TI  - Exploration of examinees' traits that affect the score of Korean Medical
      Licensing Examination.
AB  - PURPOSE: It aims to identify the effect of five variables to score of the Korean
      Medical Licensing Examinations (KMLE) for three consecutive years from 2011 to
      2013. METHODS: The number of examinees for each examination was 3,364 in 2011
      3,177 in 2012, and 3,287 in 2013. Five characteristics of examinees were set as
      variables: gender, age, graduation status, written test result (pass or fail),
      and city of medical school. A regression model was established, with the score of
      a written test as a dependent variable and with examinees' traits as variables.
      RESULTS: The regression coefficients in all variables, except the city of medical
      school, were statistically significant. The variable's effect in three
      examinations appeared in the following order: result of written test, graduation
      status, age, gender, and city of medical school. CONCLUSION: written test scores
      of the KMLE revealed that female students, younger examinees, and first-time
      examinees had higher performances.

PMID- 25773515
TI  - Development of a novel observational measure for anxiety in young children: The
      Anxiety Dimensional Observation Scale.
AB  - BACKGROUND: Identifying anxiety disorders in preschool-age children represents an
      important clinical challenge. Observation is essential to clinical assessment and
      can help differentiate normative variation from clinically significant anxiety.
      Yet, most anxiety assessment methods for young children rely on parent-reports.
      The goal of this article is to present and preliminarily test the reliability and
      validity of a novel observational paradigm for assessing a range of fearful and
      anxious behaviors in young children, the Anxiety Dimensional Observation Schedule
      (Anx-DOS). METHODS: A diverse sample of 403 children, aged 3 to 6 years, and
      their mothers was studied. Reliability and validity in relation to parent reports
      (Preschool Age Psychiatric Assessment) and known risk factors, including
      indicators of behavioral inhibition (latency to touch novel objects) and
      attention bias to threat (in the dot-probe task) were investigated. RESULTS: The
      Anx-DOS demonstrated good inter-rater reliability and internal consistency.
      Evidence for convergent validity was demonstrated relative to mother-reported
      separation anxiety, social anxiety, phobic avoidance, trauma symptoms, and past
      service use. Finally, fearfulness was associated with observed latency and
      attention bias toward threat. CONCLUSIONS: Findings support the Anx-DOS as a
      method for capturing early manifestations of fearfulness and anxiety in young
      children. Multimethod assessments incorporating standardized methods for
      assessing discrete, observable manifestations of anxiety may be beneficial for
      early identification and clinical intervention efforts.

PMID- 25773517
TI  - Using Workflow Diagrams to Address Hand Hygiene in Pediatric Long-Term Care
      Facilities.
AB  - Hand hygiene (HH) in pediatric long-term care settings has been found to be sub
      optimal. Multidisciplinary teams at three pediatric long-term care facilities
      developed step-by-step workflow diagrams of commonly performed tasks highlighting
      HH opportunities. Diagrams were validated through observation of tasks and
      concurrent diagram assessment. Facility teams developed six workflow diagrams
      that underwent 22 validation observations. Four main themes emerged: 1) diagram
      specificity, 2) wording and layout, 3) timing of HH indications, and 4)
      environmental hygiene. The development of workflow diagrams is an opportunity to
      identify and address the complexity of HH in pediatric long-term care facilities.

PMID- 25773518
TI  - Nitric oxide is reduced to HNO by proton-coupled nucleophilic attack by
      ascorbate, tyrosine, and other alcohols. A new route to HNO in biological media?
AB  - The role of NO in biology is well established. However, an increasing body of
      evidence suggests that azanone (HNO), could also be involved in biological
      processes, some of which are attributed to NO. In this context, one of the most
      important and yet unanswered questions is whether and how HNO is produced in
      vivo. A possible route concerns the chemical or enzymatic reduction of NO. In the
      present work, we have taken advantage of a selective HNO sensing method, to show
      that NO is reduced to HNO by biologically relevant alcohols with moderate
      reducing capacity, such as ascorbate or tyrosine. The proposed mechanism involves
      a nucleophilic attack to NO by the alcohol, coupled to a proton transfer (PCNA:
      proton-coupled nucleophilic attack) and a subsequent decomposition of the so
      produced radical to yield HNO and an alkoxyl radical. 

PMID- 25773520
TI  - Enhanced diversity and aflatoxigenicity in interspecific hybrids of Aspergillus
      flavus and Aspergillus parasiticus.
AB  - Aspergillus flavus and A. parasiticus are the two most important aflatoxin
      producing fungi responsible for the contamination of agricultural commodities
      worldwide. Both species are heterothallic and undergo sexual reproduction in
      laboratory crosses. Here we examine the possibility of interspecific matings
      between A. flavus and A. parasiticus. These species can be distinguished
      morphologically and genetically, as well as by their mycotoxin profiles.
      Aspergillus flavus produces both B aflatoxins and cyclopiazonic acid (CPA), B
      aflatoxins or CPA alone, or neither mycotoxin; Aspergillus parasiticus produces B
      and G aflatoxins or the aflatoxin precursor O-methylsterigmatocystin, but not
      CPA. Only four of forty-five attempted interspecific crosses between opposite
      mating types of A. flavus and A. parasiticus were fertile and produced viable
      ascospores. Single ascospore strains from each cross were shown to be recombinant
      hybrids using multilocus genotyping and array comparative genome hybridization.
      Conidia of parents and their hybrid progeny were haploid and predominantly
      monokaryons and dikaryons based on flow cytometry. Multilocus phylogenetic
      inference showed that experimental hybrid progeny were grouped with naturally
      occurring A. flavus L strain and A. parasiticus. Higher total aflatoxin
      concentrations in some F1 progeny strains compared to midpoint parent aflatoxin
      levels indicate synergism in aflatoxin production; moreover, three progeny
      strains synthesized G aflatoxins that were not produced by the parents, and there
      was evidence of allopolyploidization in one strain. These results suggest that
      hybridization is an important diversifying force resulting in the genesis of
      novel toxin profiles in these agriculturally important fungi. 

PMID- 25773519
TI  - Molecular mechanisms of MLL-associated leukemia.
AB  - Gene rearrangements of the mixed lineage leukemia (MLL) gene cause aggressive
      leukemia. The fusion of MLL and its partner genes generates various MLL fusion
      genes, and their gene products trigger aberrant self-renewal of hematopoietic
      progenitors leading to leukemia. Since the identification of the MLL gene two
      decades ago, a substantial amount of information has been obtained regarding the
      mechanisms by which MLL mutations cause leukemia. Wild-type MLL maintains the
      expression of Homeobox (HOX) genes during development. MLL activates the
      expression of posterior HOX-A genes in the hematopoietic lineage to stimulate the
      expansion of immature progenitors. MLL fusion proteins constitutively activate
      the HOX genes, causing aberrant self-renewal. The modes of transcriptional
      activation vary depending on the fusion partners and can be categorized into at
      least four groups. Here I review the recent progress in research related to the
      molecular mechanisms of MLL fusion-dependent leukemogenesis. 

PMID- 25773521
TI  - Biosynthesis of odd-chain fatty alcohols in Escherichia coli.
AB  - Engineered microbes offer the opportunity to design and implement artificial
      molecular pathways for renewable production of tailored chemical commodities.
      Targeted biosynthesis of odd-chain fatty alcohols is very challenging in microbe,
      due to the specificity of fatty acids synthase for two-carbon unit elongation.
      Here, we developed a novel strategy to directly tailor carbon number in fatty
      aldehydes formation step by incorporating alpha-dioxygenase (alphaDOX) from Oryza
      sativa (rice) into Escherichia coli alphaDOX oxidizes Cn fatty acids (even-chain)
      to form Cn-1 fatty aldehydes (odd-chain). Through combining alphaDOX with fatty
      acyl-acyl carrier protein (-ACP) thioesterase (TE) and aldehyde reductase (AHR),
      the medium odd-chain fatty alcohols profile (C11, C13, C15) was firstly
      established in E. coli. Also, medium even-chain alkanes (C12, C14) were obtained
      by substitution of AHR to aldehyde decarbonylase (AD). The titer of odd-chain
      fatty alcohols was improved from 7.4mg/L to 101.5mg/L in tube cultivation by
      means of fine-tuning endogenous fatty acyl-ACP TE (TesA'), alphaDOX, AHRs and the
      genes involved in fatty acids metabolism pathway. Through high cell density fed
      batch fermentation, a titer of 1.95g/L odd-chain fatty alcohols was achieved,
      which was the highest reported titer in E. coli. Our system has greatly expanded
      the current microbial fatty alcohols profile that provides a new brand solution
      for producing complex and desired molecules in microbes. 

PMID- 25773522
TI  - An unprecedented alteration in mode of action of IsCT resulting its translocation
      into bacterial cytoplasm and inhibition of macromolecular syntheses.
AB  - IsCT, a 13-residue, non-cell-selective antimicrobial peptide is comprised of
      mostly hydrophobic residues and lesser cationic residues. Assuming that placement
      of an additional positive charge in the non-polar face of IsCT could reduce its
      hydrophobic interaction, resulting in its reduction of cytotoxicity, an analog,
      I9K-IsCT was designed. Two more analogs, namely, E7K-IsCT and E7K,I9K-IsCT, were
      designed to investigate the impact of positive charges in the polar face as well
      as polar and non-polar faces at a time. These amino acid substitutions resulted
      in a significant enhancement of therapeutic potential of IsCT. IsCT and E7K-IsCT
      seem to target bacterial membrane for their anti-bacterial activity. However, I9K
      IsCT and E7K,I9K-IsCT inhibited nucleic acid and protein syntheses in tested E.
      coli without perturbing its membrane. This was further supported by the
      observation that NBD-IsCT localized onto bacterial membrane while NBD-labeled I9K
      IsCT and E7K,I9K-IsCT translocated into bacterial cytoplasm. Interestingly, IsCT
      and E7K-IsCT were significantly helical while I9K-IsCT and E7K,I9K-IsCT were
      mostly unstructured with no helix content in presence of mammalian and bacterial
      membrane-mimetic lipid vesicles. Altogether, the results identify two novel cell
      selective analogs of IsCT with new prototype amino acid sequences that can
      translocate into bacterial cytoplasm without any helical structure and inhibit
      macromolecular syntheses.

PMID- 25773523
TI  - Cross-sectional time trends in psychological and somatic health complaints among
      adolescents: a structural equation modelling analysis of 'Health Behaviour in
      School-aged Children' data from Switzerland.
AB  - PURPOSE: This study examined cross-sectional time trends in health complaints
      among adolescents living in Switzerland, including differences between population
      subgroups and sources of differential response to items. METHODS: Swiss data were
      analysed from the Health Behaviour in School-aged Children (HBSC; including 11-15
      years old) from 1994 (n = 7008), 1998 (n = 8296), 2002 (n = 9066) and 2006 (n =
      9255). Structural equation modelling was used to assess (1) the structure of the
      HBSC Symptom Checklist (HBSC-SCL; questionnaire, which asks about the frequency
      of eight health complaints) and (2) associations between the HBSC-SCL with year
      of data collection and demographic characteristics of the participants. RESULTS:
      Two correlated factors fitted the data better than a single factor. The
      psychological factor included the items 'feeling low,' 'irritability and bad
      temper,' 'nervousness' and 'difficulties in getting to sleep,' and the somatic
      factor the items 'headache', 'backache', 'stomach ache' and 'dizziness'. Relative
      to 1994, lower levels of psychological health complaints were experienced in
      1998, 2002 and 2006. However, the changes were only minor. In contrast, somatic
      health complaints increased monotonically over the years of the survey.
      Experiencing psychological and somatic health complaints was more pronounced with
      age among females relative to males and was associated with living in particular
      language regions of Switzerland. CONCLUSIONS: Different cross-sectional time
      trends were identified for the psychological and somatic latent variables,
      indicating that both factors should be investigated when studying period effects.

PMID- 25773524
TI  - Psychiatric disorders prior to dating initiation and physical dating violence
      before age 21: findings from the National Comorbidity Survey Replication (NCS-R).
AB  - PURPOSE: Poor mental health is associated with teen dating violence (TDV), but
      whether there are specific types of psychiatric disorders that could be targeted
      with intervention to reduce TDV remains unknown. METHODS: Multivariable logistic
      regression models were used to assess the associations of psychiatric disorders
      that emerged prior to dating initiation with subsequent physical dating violence
      in a nationally representative sample from the National Comorbidity Survey
      Replication, adjusting statistically for adverse childhood experiences. RESULTS:
      In adjusted models, internalizing disorders (AOR 1.14, 95 % CI 1.04,1.25; no sex
      differences noted) and externalizing disorders (males: AOR 1.28, 95 % CI 1.10,
      1.49; females: AOR 1.85, 95 % CI 1.55, 2.21) were associated with subsequent
      involvement in any physical dating violence victimization or perpetration before
      the age of 21. Those at greatest risk included girls with ADHD and a substance
      use disorder, in particular. CONCLUSIONS: The range of psychiatric disorders
      associated with TDV is broader than has generally been recognized for both boys
      and girls. Clinical and public health prevention programs should incorporate
      strategies for addressing multiple pathways through which poor mental health may
      put adolescents at risk for TDV.

PMID- 25773525
TI  - Association between witnessing traumatic events and psychopathology in the South
      African Stress and Health Study.
AB  - BACKGROUND: The high burden of witnessing traumatic events has been demonstrated
      in previous research in South Africa. However, previous work has focused on PTSD
      rather than a broader range of psychopathological outcomes. This study examined
      the association between witnessing trauma and multiple outcomes including mood,
      anxiety, and substance use disorders. METHODS: Regression models measured the
      odds of mood, anxiety, and substance use disorders among those who reported
      witnessing in the South African Stress and Health Study. Discrete-time survival
      analysis was used to examine whether witnessing was associated with earlier onset
      of mental disorders. RESULTS: Witnessing trauma was more commonly reported among
      males and those with low-average education. Posttraumatic stress disorder, mood,
      and anxiety disorders varied significantly with witnessing status, and witnessing
      was associated with exposure to a higher number of traumatic events compared to
      other types of traumatic events. Respondents reporting witnessing trauma had
      elevated odds of mood and anxiety disorders, but not substance use disorders.
      CONCLUSION: Witnessing trauma is common in the South African population and
      results in increased risk of mood and anxiety disorders. Interventions aimed at
      reducing the burden of trauma and its outcomes must now increase their focus on
      bystanders and other observers, rather than just focusing on those directly
      affected.

PMID- 25773526
TI  - Cytoplasmic, rather than nuclear-DNA, insufficiencies as the major cause of poor
      competence of vitrified oocytes.
AB  - To unravel the differential contributions of nuclear-DNA and cytoplasm to the
      poor 'competence' of oocytes after cryopreservation, reciprocal exchange of
      metaphase II-spindle chromosomal complex (karyoplast) between vitrified and fresh
      oocytes was carried out in an ovine animal model. Karyoplast exchange per se was
      accomplished with high efficiency and in-vitro development of oocytes
      reconstituted with fresh-karyoplast and vitrified-cytoplast (FK/VC) showed no
      improvement over VK/VC and control-vitrification oocytes. Blastocyst development
      of oocytes that were reconstituted with vitrified-karyoplast and fresh-cytoplast
      (VK/FC) approached that of fresh-controls, however, and was significantly higher
      than FK/VC, VK/VC, and control-vitrification (all P <= 0.05). These results point
      toward 'cytoplasmic insufficiencies' as the main cause of poor 'competence' of
      matured oocytes after vitrification. 

PMID- 25773527
TI  - Processing, selecting and ritualizing: ambivalent relationships to semen.
AB  - Two articles on human immunodeficiency virus (HIV) and reproduction have recently
      been published in Reproductive BioMedicine Online, both describing developments
      that increase reproductive options for HIV-positive men. A study of a semen
      processing technique used at a South African hospital found that two out of 103
      processed samples tested positive for HIV DNA and none for RNA, indicating 98.1%
      and 100% effectiveness, respectively. The authors recommend semen processing
      followed by viral validation of processed sperm samples when providing assisted
      reproduction treatment to couples with an HIV-positive male partner. The other
      article reviews developments such as semen processing, antiretroviral (ARV)
      therapy and pre-exposure prophylaxis (PrEP), which have all reduced the risk of
      HIV transmission in the context of reproduction. The author also notes, however,
      that research on fertility in the context of HIV focuses almost exclusively on
      heterosexual couples, and has overlooked the links between reproduction, HIV and
      homosexuality. This article analyses the ambivalent role of semen - associated
      with both reproduction and infection - and how reproductive medicine and health
      care in different ways seek to 'get hold' of sperm. By taking this analytic
      approach, sex and parenthood can be thought of as two different but related kinds
      of intimacy and kinship. 

PMID- 25773528
TI  - Sohlh2 inhibits the apoptosis of mouse primordial follicle oocytes via C
      kit/PI3K/Akt/Foxo3a signalling pathway.
AB  - We previously reported that bone morphogenetic protein 4/drosophila mothers
      against decapentaplegic protein (BMP4/Smad) signalling pathway initiated
      primordial follicle growth and prevented oocyte apoptosis via up-regulation of
      Sohlh2 and receptor for kit ligand (c-kit). The mechanism underlying this process
      was not fully elucidated. In the present study, primary oocyte cultures were
      established from ovaries of 3-day-old female mouse pups by two-step enzyme
      digestion. Cultures were divided into Sohlh2 small interference RNA (SiRNA)
      group, negative SiRNA group, Sohlh2 overexpression plasmid group and pCAG-puro
      group. TdT (terminal deoxynucleotidyl transferase)-mediated dUDP nick-end
      labelling assay was carried out to detect the oocyte apoptosis;
      immunocytochemical staining and quantitative real time-polymerase chain reaction
      detected the expression of c-kit and Forkhead box O3a (Foxo3a); Western blot was
      performed to detect the expression of Sohlh2, C-kit, saerine/threonine kinases
      (Akt1) and Foxo3a. The results showed that Sohlh2 inhibited oocyte apoptosis and
      upregulated c-kit expression; Sohlh2 decreased the endonuclear Foxo3a via the
      upregulation of phosphorylated Akt1 (P-Akt1) and phosphorylated Foxo3a (P-Foxo3a)
      but not total Akt1 (T-Akt1) or total Foxo3a (T-Foxo3a); Sohlh2 increased P-Akt1
      but not T-Akt1; the PI3K (phosphotidylinsitol-3-kinase) inhibitor LY294002
      ameliorated the role of Sohlh2 on phosphorylation of Akt1 and Foxo3a. Sohlh2 may
      inhibit oocyte apoptosis via c-kit/PI3K/Akt/Foxo3a signalling pathway. 

PMID- 25773529
TI  - Patient pressure: is the tide of cross-border reproductive care beginning to
      turn?
AB  - Two important explanations exist for cross-border reproductive care: restrictive
      legislation at home and limited access to affordable treatment. Both have
      recently been subject to patient pressure, favouring domestic and not cross
      border services. The oppressive effect of regulation has been best illustrated in
      Italy, where legislation introduced as Law 40 in 2004 imposed restrictions on
      embryo freezing and embryo selection. After a decade of legal challenges by
      patients, the components of Law 40 have now been deemed unconstitutional in
      Italy. Similarly, a paucity of donor gametes in the UK has left many patients
      with few options but to seek donors and treatments overseas. Yet new techniques
      of donor recruitment and a revised allowance of compensation now means that some
      UK clinics can meet all requirements for donor gametes and patient matching from
      their own resources. 

PMID- 25773530
TI  - How old is too old? A contribution to the discussion on age limits for assisted
      reproduction technique access.
AB  - In 2012, the Czech Republic established the women's age limit for access to
      assisted reproduction techniques at age 49 years. In this paper, the
      acceptability of this age limit from the children's perspective in the Czech
      Republic is assessed. Although the necessity of balancing the interests of
      parents and children is acknowledged, little research has taken children's
      interests into account. We have attempted to map out 'children's interests',
      asking older children and adolescents (aged 11-25 years) how old they would
      prefer their parents to be: Czech respondents would prefer to have younger
      parents. This finding is consistent with the optimal biological childbearing age
      rather than with the current postponement to a later age. So far, assisted
      reproduction techniques have been largely regarded as a medical treatment
      justifying the current women's age limit of 49 years. Had the children's
      perspective been taken into account, this age limit might have been lower than 49
      years. We propose that reproductive health policy should adequately reflect
      multiple perspectives as an integral part of a multi-layered support system of a
      society. 

PMID- 25773531
TI  - Down-regulation of the CYP19A1 gene in cumulus cells of infertile women with
      endometriosis.
AB  - Aromatase plays a fundamental role in the establishment of oocyte quality, which
      might be compromised in infertile women with endometriosis. The expression of the
      CYP19A1 gene (that encodes aromatase) was compared in cumulus cells and
      oestradiol concentrations in the follicular fluid of infertile women with and
      without endometriosis submitted to ovarian stimulation for intracytoplasmic sperm
      injection. Cumulus cells were isolated and the expression of the CYP19A1 was
      quantitated through real-time polymerase chain reaction. Oestradiol
      concentrations in follicular fluid were measured by chemiluminescence
      immunoassay. A lower expression of the CYP19A1 in the cumulus cells of infertile
      women with endometriosis was observed compared with controls (0.17 +/- 0.13 and
      0.56 +/- 0.12, respectively), and no significant difference in the follicular
      fluid oestradiol concentrations was observed between groups. Our results show
      reduced expression of the CYP19A1 in cumulus cells of infertile women with
      endometriosis, which may play a role in the pathogenesis of endometriosis-related
      infertility. 

PMID- 25773532
TI  - Science-policy processes for transboundary water governance.
AB  - In this policy perspective, we outline several conditions to support effective
      science-policy interaction, with a particular emphasis on improving water
      governance in transboundary basins. Key conditions include (1) recognizing that
      science is a crucial but bounded input into water resource decision-making
      processes; (2) establishing conditions for collaboration and shared commitment
      among actors; (3) understanding that social or group-learning processes linked to
      science-policy interaction are enhanced through greater collaboration; (4)
      accepting that the collaborative production of knowledge about hydrological
      issues and associated socioeconomic change and institutional responses is
      essential to build legitimate decision-making processes; and (5) engaging
      boundary organizations and informal networks of scientists, policy makers, and
      civil society. We elaborate on these conditions with a diverse set of
      international examples drawn from a synthesis of our collective experiences in
      assessing the opportunities and constraints (including the role of power
      relations) related to governance for water in transboundary settings. 

PMID- 25773533
TI  - Nighttime lights and population changes in Europe 1992-2012.
AB  - Nighttime satellite photographs of Earth reveal the location of lighting and
      provide a unique view of the extent of human settlement. Nighttime lights have
      been shown to correlate with economic development and population but little
      research has been done on the link between nighttime lights and population change
      over time. We explore whether population decline is coupled with decline in
      lighted area and how the age structure of the population and GDP are reflected in
      nighttime lights. We examine Europe between the period of 1992 and 2012 using a
      Geographic Information System and regression analysis. The results suggest that
      population decline is not coupled with decline in lighted area. Instead, human
      settlement extent is more closely related to the age structure of the population
      and to GDP. We conclude that declining populations will not necessarily lead to
      reductions in the extent of land development. 

PMID- 25773536
TI  - Clinical outcomes in sensitized heart transplant patients bridged with
      ventricular assist devices.
AB  - BACKGROUND: Left ventricular assist devices (LVADs) as a bridge to transplant
      (BTT) have been known to cause allosensitization, as measured by panel-reactive
      antibody (PRA) levels. The goal of this study was to measure the impact of this
      allosensitization on outcomes. METHODS: Panel-reactive antibodies were analyzed
      in BTT patients, with sensitization defined as peak PRAs >= 10%. Baseline
      characteristics and outcomes in the two patient groups were evaluated using
      descriptive statistics, Kaplan-Meier, and regression analysis. RESULTS: Thirty
      eight patients were included in the study (17 sensitized vs. 21 non-sensitized).
      There were more women in the sensitized group (47% vs. 10%, p = 0.023). There was
      no difference in mean times to high-grade acute cellular rejection (ACR; 18.3
      months in sensitized vs. 36.9 months in non-sensitized). Five patients in the
      sensitized groups developed antibody-mediated rejection (AMR) vs. 0 in the non
      sensitized, and all five patients died (Kaplan-Meier log-rank p = 0.024). There
      was also a significant difference in the incidence of infection at the one- to
      six-month stage (52.9% vs. 19.0%, p = 0.03). CONCLUSION: Sensitization appears to
      have a negative effect on mortality. This mortality appears to be concentrated in
      patients with AMR, and we postulate that the development of AMR in a sensitized
      patient may be a predictor of mortality.

PMID- 25773535
TI  - Generation of a stable thrombin-activatable fibrinolysis inhibitor deletion
      mutant exerting full carboxypeptidase activity without activation.
AB  - BACKGROUND: Thrombin-activatable fibrinolysis inhibitor (TAFI) is a zymogen that
      can be activated to form activated TAFI (TAFIa) (Ala93-Val401) through removal of
      the N-terminal activation peptide (Phe1-Arg92). TAFIa is thermally unstable, and
      the role of the activation peptide in the activity and stability of TAFI zymogen
      remains unclear. OBJECTIVES: To better understand the role of the activation
      peptide in the activity and stability of TAFI. METHODS: We constructed a deletion
      mutant, TAFI-CIIYQ-?1-73 , in which the first 73 amino acids of the activation
      peptide are absent. The intrinsic activity and functional stability were
      determined with a chromogenic assay. The activation of TAFI-CIIYQ-?1-73 by TAFI
      activators was evaluated with western blot analysis. RESULTS: In comparison with
      TAFI-CIIYQ, the deletion mutant exerted high intrinsic activity ('full' apparent
      TAFIa activity) without cleavage by TAFI activators. TAFI-CIIYQ-?1-73 was
      cleavable by thrombin. However, in the presence of thrombomodulin, the thrombin
      mediated cleavage of TAFI-CIIYQ-?1-73 was not accelerated. TAFI-CIIYQ-?1-73
      showed a similar functional stability profile to that of TAFI-CIIYQ. Full
      cleavage by thrombin did not affect the apparent carboxypeptidase activity of
      TAFI-CIIYQ-?1-73 , but resulted in a significant loss of functional stability.
      CONCLUSIONS: A stable deletion mutant of TAFI with full carboxypeptidase activity
      without activation is described. The segment Ala74-Arg92 in the activation
      peptide contributes significantly to the role of the activation peptide in
      stabilization of the catalytic moiety in TAFI zymogen.

PMID- 25773537
TI  - Microfluidic-aided genotyping of zebrafish in the first 48 h with 100% viability.
AB  - This paper introduces an innovative method for genotyping 1-2 days old zebrafish
      embryos, without sacrificing the life/health of the embryos. The method utilizes
      microfluidic technology to extract and collect a small amount of genetic material
      from the chorionic fluid or fin tissue of the embryo. Then, using conventional
      DNA extraction, PCR amplification, and high resolution melt analysis with
      fluorescent DNA detection techniques, the embryo is genotyped. The chorionic
      fluid approach was successful 78% of the time while the fin clipping method was
      successful 100% of the time. Chorionic fluid was shown to only contain DNA from
      the embryo and not from the mother. These results suggest a novel method to
      genotype zebrafish embryos that can facilitate high-throughput screening, while
      maintaining 100% viability of the embryo.

PMID- 25773534
TI  - Mycophenolate mofetil therapy for steroid-resistant IgA nephropathy with the
      nephrotic syndrome in children.
AB  - BACKGROUND: Immunoglobulin A nephropathy (IgAN) presents as nephrotic syndrome
      (NS) relatively rarely, and the current treatment experience of IgAN patients
      with NS is mostly with adults. The objective of our study was to investigate the
      efficacy of corticosteroids and mycophenolate mofetil (MMF) in treating childhood
      immunoglobulin A nephropathy (IgAN) with nephrotic syndrome. METHODS: A total of
      58 children (39 boys and 19 girls) diagnosed with nephrotic syndrome and primary
      IgAN were enrolled in the study. All the patients were administered prednisone 2
      mg/kg per day for 8 weeks. Steroid-resistant patients were treated with the
      combined use of MMF (dose of 20 ~ 30 mg/kg per day) and prednisone for 6-12
      months. The prednisone dose was reduced stepwise during the combined treatment.
      RESULTS: Of the 58 children, 14 were steroid-sensitive (M, S, and T variants of
      the Oxford classification were 0 in most children), and 44 cases who presented
      serious pathological damage to the kidney were steroid-resistant. The estimated
      glomerular filtration rate (eGFR) of the steroid-resistant children (86.69 +/-
      26.85 ml/min/1.73 m(2)) was significantly lower (P < 0.05) than that of the
      steroid-sensitive children (106.89 +/- 26.94 ml/min/1.73 m(2)). After 4 months of
      combined MMF treatment in 33 steroid-resistant children, complete remission of
      proteinuria was found in 21 cases, partial remission of proteinuria in 6 cases,
      and no response was found in 6 cases. Except for the T variant, other variants of
      the Oxford classification, including M, E, and S morphological variables, was not
      significantly different among patients complete remission, those with partial
      remission, and those with no response. The eGFR of children with complete
      remission of proteinuria (100.04 +/- 18.47 ml/min/1.73 m(2)), that of those with
      partial remission (92.24 +/- 27.63 ml/min/1.73 m(2)), and that of those with no
      response (72.17 +/- 27.55 ml/min/1.73 m(2)) were significantly different (P <
      0.05). CONCLUSION: Corticosteroid therapy showed satisfactory efficacy in IgAN
      children with nephrotic syndrome and slight pathological damage. The effect of
      MMF was good for steroid-resistant IgAN children, but poor for those with tubular
      atrophy/interstitial fibrosis and renal function impairment.

PMID- 25773538
TI  - Variation in infection prevention practices in dialysis facilities: results from
      the national opportunity to improve infection control in ESRD (End-Stage Renal
      Disease) project.
AB  - OBJECTIVE To observe patient care across hemodialysis facilities enrolled in the
      National Opportunity to Improve Infection Control in ESRD (end-stage renal
      disease) (NOTICE) project in order to evaluate adherence to evidence-based
      practices aimed at prevention of infection. SETTING AND PARTICIPANTS Thirty-four
      hemodialysis facilities were randomly selected from among 772 facilities in 4 end
      stage renal disease participating networks. Facility selection was stratified on
      dialysis organization affiliation, size, socioeconomic status, and urban/rural
      status. MEASUREMENTS Trained infection control evaluators used an infection
      control worksheet to observe 73 distinct infection control practices at the
      hemodialysis facilities, from October 1, 2011, through January 31, 2012. RESULTS
      There was considerable variation in infection control practices across enrolled
      facilities. Overall adherence to recommended practices was 68% (range, 45%-92%)
      across all facilities. Overall adherence to expected hand hygiene practice was
      72% (range, 10%-100%). Compliance to hand hygiene before and after procedures was
      high; however, during procedures hand hygiene compliance averaged 58%. Use of
      chlorhexidine as the specific agent for exit site care was 19% overall but varied
      from 0% to 35% by facility type. The 8 checklists varied in the frequency of
      perfect performance from 0% for meeting every item on the checklist for
      disinfection practices to 22% on the arteriovenous access practices at
      initiation. CONCLUSIONS Our findings suggest that there are many areas for
      improvement in hand hygiene and other infection prevention practices in end-stage
      renal disease. These NOTICE project findings will help inform the development of
      a larger quality improvement initiative at dialysis facilities.

PMID- 25773539
TI  - The chromatin regulator Brpf1 regulates embryo development and cell
      proliferation.
AB  - With hundreds of chromatin regulators identified in mammals, an emerging issue is
      how they modulate biological and pathological processes. BRPF1 (bromodomain- and
      PHD finger-containing protein 1) is a unique chromatin regulator possessing two
      PHD fingers, one bromodomain and a PWWP domain for recognizing multiple histone
      modifications. In addition, it binds to the acetyltransferases MOZ, MORF, and
      HBO1 (also known as KAT6A, KAT6B, and KAT7, respectively) to promote complex
      formation, restrict substrate specificity, and enhance enzymatic activity. We
      have recently showed that ablation of the mouse Brpf1 gene causes embryonic
      lethality at E9.5. Here we present systematic analyses of the mutant animals and
      demonstrate that the ablation leads to vascular defects in the placenta, yolk
      sac, and embryo proper, as well as abnormal neural tube closure. At the cellular
      level, Brpf1 loss inhibits proliferation of embryonic fibroblasts and
      hematopoietic progenitors. Molecularly, the loss reduces transcription of a
      ribosomal protein L10 (Rpl10)-like gene and the cell cycle inhibitor p27, and
      increases expression of the cell-cycle inhibitor p16 and a novel protein
      homologous to Scp3, a synaptonemal complex protein critical for chromosome
      association and embryo survival. These results uncover a crucial role of Brpf1 in
      controlling mouse embryo development and regulating cellular and gene expression
      programs. 

PMID- 25773540
TI  - Selective Distal Enhancer Control of the Mmp13 Gene Identified through Clustered
      Regularly Interspaced Short Palindromic Repeat (CRISPR) Genomic Deletions.
AB  - Matrix metalloproteinase 13 (Mmp13, collagenase-3) plays an essential role in
      bone metabolism and mineral homeostasis. It is regulated by numerous factors,
      including BMP-2, parathyroid hormone, and 1alpha,25-dihydroxyvitamin D3
      (1,25(OH)2D3), through transcription factors such as Runt-related transcription
      factor 2 (RUNX2), CCAAT/enhancer-binding protein beta (C/EBPbeta), OSX, and
      vitamin D receptor (VDR). During osteoblast maturation, the basal expression of
      Mmp13 and its sensitivity to 1,25(OH)2D3 are strikingly increased. In this
      report, ChIP-sequencing analysis in mouse preosteoblasts revealed that the Mmp13
      gene was probably regulated by three major enhancers located -10, -20, and -30 kb
      upstream of the gene promoter, occupied by activated VDR and prebound C/EBPbeta
      and RUNX2, respectively. Initially, bacterial artificial chromosome clone
      recombineering and traditional mutagenesis defined binding sites for VDR and
      RUNX2. We then employed a CRISPR/Cas9 gene editing approach to delete the -10 and
      -30 kb Mmp13 enhancers, a region proximal to the promoter, and VDR or RUNX2. VDR
      mediated up-regulation of Mmp13 transcription was completely abrogated upon
      removal of the -10 kb enhancer, resulting in a 1,25(OH)2D3-directed repression of
      Mmp13. Deletion of either the -30 kb enhancer or RUNX2 resulted in a complete
      loss of basal transcript activity and a ChIP-identified destabilization of the
      chromatin enhancer environment and factor binding. Whereas enhancer deletions
      only affected Mmp13 expression, the RUNX2 deletion led to changes in gene
      expression, a reduction in cellular proliferation, and an inability to
      differentiate. We conclude that the Mmp13 gene is regulated via at least three
      specific distal enhancers that display independent activities yet are able to
      integrate response from multiple signaling pathways in a model of activation and
      suppression. 

PMID- 25773541
TI  - Hepatitis E: A disease of reemerging importance.
AB  - Hepatitis E virus (HEV) is the most common cause of acute viral hepatitis
      worldwide. Originally considered to be restricted to humans, it is now clear that
      HEV and HEV-like viruses have several animal reservoirs with complex ecology and
      genetic diversity, as exemplified by the recent discovery of HEV in dromedaries,
      a previously underestimated reservoir of zoonotic viruses prior to the emergence
      of Middle East Respiratory Syndrome coronavirus. Zoonotic foodborne transmission
      from pigs and feral animals such as wild boar is of increasing importance in the
      rapidly industrializing countries of the Asia Pacific region. Such zoonotic
      hepatitis E infection has particular relevance to the increasing population
      living with immunosuppression, due to the risk of chronic hepatitis E in these
      patients. Fortunately, major strides have been made recently in the management of
      chronic hepatitis E patients. Furthermore, an effective vaccine is also available
      that promises better control of hepatitis E burden in the near future. This
      review highlights these major recent developments in the epidemiology, treatment,
      and prevention of hepatitis E. 

PMID- 25773543
TI  - Transverse testis ectopia: diagnostic and management algorithm.

PMID- 25773544
TI  - A high-throughput method for quantifying metabolically active yeast cells.
AB  - By redesigning the established methylene blue reduction test for bacteria and
      yeast, we present a cheap and efficient methodology for quantitative physiology
      of eukaryotic cells applicable for high-throughput systems. Validation of the
      method in fermenters and high-throughput systems proved equivalent, displaying
      reduction curves that interrelated directly with CFU counts. For growth rate
      estimation, the methylene blue reduction test (MBRT) proved superior, since the
      discriminatory nature of the method allowed for the quantification of
      metabolically active cells only, excluding dead cells. The drop in metabolic
      activity associated with the diauxic shift in yeast proved more pronounced for
      the MBRT-derived curve compared with OD curves, consistent with a dramatic shift
      in the ratio between live and dead cells at this metabolic event. This method
      provides a tool with numerous applications, e.g. characterizing the death phase
      of stationary phase cultures, or in drug screens with pathogenic yeasts.

PMID- 25773545
TI  - Preoperative high levels of serum vascular endothelial growth factor are a
      prognostic marker for poor outcome after surgical treatment of renal cell
      carcinoma.
AB  - OBJECTIVE: The aim of this study was to determine whether concentrations of
      vascular endothelial growth factor (VEGF) in blood taken preoperatively can
      predict subtype, survival and recurrence in patients with renal cell carcinoma
      (RCC). MATERIALS AND METHODS: The patient group consisted of 124 patients with an
      RCC that was surgically removed with nephrectomy or nephron-sparing surgery at
      Haukeland University Hospital from 2007 to 2010. All subtypes and stages were
      included. Preoperative blood samples were taken on the day of surgery, and the
      samples were prepared and frozen at -80  degrees C. The level of VEGF in serum
      was analysed using Luminex(r) immunobead technology. The patients were followed
      until death or to 31 October 2014 (>4.5 years). RESULTS: Patients with higher
      levels of VEGF were more likely to have clear cell RCC [odds ratio (OR) 2.43, p =
      0.046], as were older patients (OR 1.04, p = 0.024). In a multivariate analysis,
      high VEGF, stage and nuclear grade all had a significant predictive value for
      cancer-specific survival (OR 4.56, p = 0.017; OR 11.54, p < 0.001; and OR 7.85, p
      = 0.015, respectively). VEGF, stage and nuclear grade predicted recurrence in
      patients presumed to have been radically treated (OR 4.37, p = 0.03; OR 5.02, p =
      0.011; and OR 6.57, p = 0.008, respectively). CONCLUSIONS: Tumour stage and a
      high level of serum VEGF were predictors for an increased risk of recurrence and
      cancer-specific death. Furthermore, the study showed that serum VEGF may be used
      to determine the subtype of RCC preoperatively.

PMID- 25773546
TI  - Potential application of machine learning in health outcomes research and some
      statistical cautions.
AB  - Traditional analytic methods are often ill-suited to the evolving world of health
      care big data characterized by massive volume, complexity, and velocity. In
      particular, methods are needed that can estimate models efficiently using very
      large datasets containing healthcare utilization data, clinical data, data from
      personal devices, and many other sources. Although very large, such datasets can
      also be quite sparse (e.g., device data may only be available for a small subset
      of individuals), which creates problems for traditional regression models. Many
      machine learning methods address such limitations effectively but are still
      subject to the usual sources of bias that commonly arise in observational
      studies. Researchers using machine learning methods such as lasso or ridge
      regression should assess these models using conventional specification tests. 

PMID- 25773547
TI  - Clinical trials provide essential evidence, but rarely offer a vehicle for cost
      effectiveness analysis.

PMID- 25773548
TI  - Dynamic simulation in health care comes of age.

PMID- 25773549
TI  - Merging regulatory and reimbursement needs in clinical trials.

PMID- 25773550
TI  - Selecting a dynamic simulation modeling method for health care delivery research
      part 2: report of the ISPOR Dynamic Simulation Modeling Emerging Good Practices
      Task Force.
AB  - In a previous report, the ISPOR Task Force on Dynamic Simulation Modeling
      Applications in Health Care Delivery Research Emerging Good Practices introduced
      the fundamentals of dynamic simulation modeling and identified the types of
      health care delivery problems for which dynamic simulation modeling can be used
      more effectively than other modeling methods. The hierarchical relationship
      between the health care delivery system, providers, patients, and other
      stakeholders exhibits a level of complexity that ought to be captured using
      dynamic simulation modeling methods. As a tool to help researchers decide whether
      dynamic simulation modeling is an appropriate method for modeling the effects of
      an intervention on a health care system, we presented the System, Interactions,
      Multilevel, Understanding, Loops, Agents, Time, Emergence (SIMULATE) checklist
      consisting of eight elements. This report builds on the previous work,
      systematically comparing each of the three most commonly used dynamic simulation
      modeling methods-system dynamics, discrete-event simulation, and agent-based
      modeling. We review criteria for selecting the most suitable method depending on
      1) the purpose-type of problem and research questions being investigated, 2) the
      object-scope of the model, and 3) the method to model the object to achieve the
      purpose. Finally, we provide guidance for emerging good practices for dynamic
      simulation modeling in the health sector, covering all aspects, from the
      engagement of decision makers in the model design through model maintenance and
      upkeep. We conclude by providing some recommendations about the application of
      these methods to add value to informed decision making, with an emphasis on
      stakeholder engagement, starting with the problem definition. Finally, we
      identify areas in which further methodological development will likely occur
      given the growing "volume, velocity and variety" and availability of "big data"
      to provide empirical evidence and techniques such as machine learning for
      parameter estimation in dynamic simulation models. Upon reviewing this report in
      addition to using the SIMULATE checklist, the readers should be able to identify
      whether dynamic simulation modeling methods are appropriate to address the
      problem at hand and to recognize the differences of these methods from those of
      other, more traditional modeling approaches such as Markov models and decision
      trees. This report provides an overview of these modeling methods and examples of
      health care system problems in which such methods have been useful. The primary
      aim of the report was to aid decisions as to whether these simulation methods are
      appropriate to address specific health systems problems. The report directs
      readers to other resources for further education on these individual modeling
      methods for system interventions in the emerging field of health care delivery
      science and implementation. 

PMID- 25773551
TI  - Cost-effectiveness analysis alongside clinical trials II-An ISPOR Good Research
      Practices Task Force report.
AB  - Clinical trials evaluating medicines, medical devices, and procedures now
      commonly assess the economic value of these interventions. The growing number of
      prospective clinical/economic trials reflects both widespread interest in
      economic information for new technologies and the regulatory and reimbursement
      requirements of many countries that now consider evidence of economic value along
      with clinical efficacy. As decision makers increasingly demand evidence of
      economic value for health care interventions, conducting high-quality economic
      analyses alongside clinical studies is desirable because they broaden the scope
      of information available on a particular intervention, and can efficiently
      provide timely information with high internal and, when designed and analyzed
      properly, reasonable external validity. In 2005, ISPOR published the Good
      Research Practices for Cost-Effectiveness Analysis Alongside Clinical Trials: The
      ISPOR RCT-CEA Task Force report. ISPOR initiated an update of the report in 2014
      to include the methodological developments over the last 9 years. This report
      provides updated recommendations reflecting advances in several areas related to
      trial design, selecting data elements, database design and management, analysis,
      and reporting of results. Task force members note that trials should be designed
      to evaluate effectiveness (rather than efficacy) when possible, should include
      clinical outcome measures, and should obtain health resource use and health state
      utilities directly from study subjects. Collection of economic data should be
      fully integrated into the study. An incremental analysis should be conducted with
      an intention-to-treat approach, complemented by relevant subgroup analyses.
      Uncertainty should be characterized. Articles should adhere to established
      standards for reporting results of cost-effectiveness analyses. Economic studies
      alongside trials are complementary to other evaluations (e.g., modeling studies)
      as information for decision makers who consider evidence of economic value along
      with clinical efficacy when making resource allocation decisions.

PMID- 25773552
TI  - Economic evaluation of tocilizumab monotherapy compared to adalimumab monotherapy
      in the treatment of severe active rheumatoid arthritis.
AB  - OBJECTIVES: To estimate the cost-effectiveness of tocilizumab (TCZ) monotherapy
      (Mono) versus adalimumab (ADA) Mono from the US payer perspective in patients
      with rheumatoid arthritis for whom methotrexate is inappropriate. METHODS: We
      compared TCZ Mono (8 mg/kg monthly) with ADA Mono (40 mg every other week), using
      efficacy results from a head-to-head study, ADalimumab ACTemrA (ADACTA). We
      calculated the incremental cost per responder (achievement of American College of
      Rheumatology [ACR] 20% improvement criteria, ACR 50% improvement criteria, ACR
      70% improvement criteria, or low disease activity score) for TCZ versus ADA at 6
      months. A patient-level simulation was used to estimate the lifetime incremental
      cost per quality-adjusted life-year (QALY) of initiating treatment with TCZ Mono
      versus ADA Mono. Both drugs are followed by an etanercept-certolizumab-palliative
      care sequence. Nonresponders discontinue at 6 months; responders experience a
      constant probability of discontinuation. Discontinuers move to the next
      treatment. ACR responses produce changes in the Health Assessment Questionnaire
      (HAQ) score. We mapped the HAQ score to utility to estimate QALYs. Costs include
      those related to hospitalization and those related to treatment (drug
      acquisition, administration, and monitoring). Probabilistic and one-way
      sensitivity analyses were conducted, along with several scenario analyses.
      RESULTS: Compared with ADA, TCZ was more effective, with an estimated 6-month
      incremental cost ranging from $6,570 per additional low disease activity score
      achiever to $14,265 per additional ACR 70% improvement criteria responder. The
      lifetime incremental cost-effectiveness ratio was $36,944/QALY. CONCLUSIONS: TCZ
      Mono is projected to be cost-effective compared with ADA Mono in patients with
      severe rheumatoid arthritis for whom methotrexate is not appropriate, from a US
      payer perspective.

PMID- 25773553
TI  - Strengthening tuberculosis control overseas: who benefits?
AB  - BACKGROUND: Although tuberculosis is a major cause of morbidity and mortality
      worldwide, available funding falls far short of that required for effective
      control. Economic and spillover consequences of investments in the treatment of
      tuberculosis are unclear, particularly when steep gradients in the disease and
      response are linked by population movements, such as that between Papua New
      Guinea (PNG) and the Australian cross-border region. OBJECTIVE: To undertake an
      economic evaluation of Australian support for the expansion of basic Directly
      Observed Treatment, Short Course in the PNG border area of the South Fly from the
      current level of 14% coverage. METHODS: Both cost-utility analysis and cost
      benefit analysis were applied to models that allow for population movement across
      regions with different characteristics of tuberculosis burden, transmission, and
      access to treatment. Cost-benefit data were drawn primarily from estimates
      published by the World Health Organization, and disease transmission data were
      drawn from a previously published model. RESULTS: Investing $16 million to
      increase basic Directly Observed Treatment, Short Course coverage in the South
      Fly generates a net present value of roughly $74 million for Australia
      (discounted 2005 dollars). The cost per disability-adjusted life-year averted and
      quality-adjusted life-year saved for PNG is $7 and $4.6, respectively.
      CONCLUSIONS: Where regions with major disparities in tuberculosis burden and
      health system resourcing are connected through population movements, investments
      in tuberculosis control are of mutual benefit, resulting in net health and
      economic gains on both sides of the border. These findings are likely to inform
      the case for appropriate investment in tuberculosis control globally.

PMID- 25773554
TI  - Comparing the cost-effectiveness of rituximab maintenance and radioimmunotherapy
      consolidation versus observation following first-line therapy in patients with
      follicular lymphoma.
AB  - BACKGROUND: Phase 3 randomized trials have shown that maintenance rituximab (MR)
      therapy or radioimmunotherapy (RIT) consolidation following frontline therapy can
      improve progression-free survival for patients with follicular lymphoma (FL), but
      the cost-effectiveness of these approaches with respect to observation has not
      been examined using a common modeling framework. OBJECTIVES: To evaluate and
      compare the economic impact of MR and RIT consolidation versus observation,
      respectively, following the first-line induction therapy for patients with
      advanced-stage FL. METHODS: We developed Markov models to estimate patients'
      lifetime costs, quality-adjusted life-years (QALYs), and life-years (LYs) after
      MR, RIT, and observation following frontline FL treatment from the US payer's
      perspective. Progression risks, adverse event probabilities, costs, and utilities
      were estimated from clinical data of Primary RItuximab and MAintenance (PRIMA)
      trial, Eastern Cooperative Oncology Group (ECOG) trial (for MR), and First-line
      Indolent Trial (for RIT) and the published literature. We evaluated the
      incremental cost-effectiveness ratio for direct comparisons between MR/RIT and
      observation. Model robustness was addressed by one-way and probabilistic
      sensitivity analyses. RESULTS: Compared with observation, MR provided an
      additional 1.089 QALYs (1.099 LYs) and 1.399 QALYs (1.391 LYs) on the basis of
      the PRIMA trial and the ECOG trial, respectively, and RIT provided an additional
      1.026 QALYs (1.034 LYs). The incremental cost per QALY gained was $40,335 (PRIMA)
      or $37,412 (ECOG) for MR and $40,851 for RIT. MR and RIT had comparable
      incremental QALYs before first progression, whereas RIT had higher incremental
      costs of adverse events due to higher incidences of cytopenias. CONCLUSIONS: MR
      and RIT following frontline FL therapy demonstrated favorable and similar cost
      effectiveness profiles. The model results should be interpreted within the
      specific clinical settings of each trial. Selection of MR, RIT, or observation
      should be based on patient characteristics and expected trade-offs for these
      alternatives.

PMID- 25773555
TI  - Effect of adherence and insulin delivery system on clinical and economic outcomes
      among patients with type 2 diabetes initiating insulin treatment.
AB  - BACKGROUND: Adherence to insulin affects real-world health outcomes and may
      itself be affected by the choice of insulin delivery device (pen or
      vial/syringe). The choice of insulin delivery device may also have direct effects
      on effectiveness. OBJECTIVE: This study aimed to estimate the effects of insulin
      adherence and delivery device on real-world health outcomes. METHODS: This study
      included adults with type 2 diabetes mellitus initiating insulin, with continuous
      health plan insurance for 6 or more months before initiation (baseline) and 1 or
      more year after. Measured outcomes included glycosylated hemoglobin (Hb A1c)
      reduction, hospitalization rate, total health care costs, and pharmacy costs over
      1 year of follow-up. Adherence (defined as having insulin fills sufficient for
      the entire quarter), pen or vial/syringe use, and disease-related patient
      characteristics were assessed in each quarter. To account for the time-varying
      relationship between adherence, patient characteristics, and outcomes, marginal
      structural generalized linear models were used to estimate the effect of
      adherence and device use. Mean outcomes were predicted for different combinations
      of adherence and device choice. RESULTS: Among the 13,428 patients (mean age 54
      years; 46% women; baseline Hb A1c 9.3%), adherent pen users had greater
      reductions in Hb A1c (-0.35%; P = 0.045), lower hospitalization rates (-0.36; P <
      0.01), and higher pharmacy costs ($2923; P < 0.01) than did nonadherent vial
      users, and similar total health care costs ($3906 lower; P = 0.1). Pen use and
      adherent vial use decreased hospitalization rate and increased pharmacy but not
      total costs. CONCLUSIONS: Adherence and pen use have beneficial effects on
      patients' real-world outcomes, with the most favorable effects attributable to
      adherent pen use.

PMID- 25773556
TI  - Predictors of self-reported adherence to antihypertensive medicines: a
      multinational, cross-sectional survey.
AB  - BACKGROUND: Nonadherence to antihypertensive medicines limits their
      effectiveness, increases the risk of adverse health outcome, and is associated
      with significant health care costs. The multiple causes of nonadherence differ
      both within and between patients and are influenced by patients' care settings.
      OBJECTIVES: The objective of this article was to identify determinants of patient
      nonadherence to antihypertensive medicines, drawing from psychosocial and
      economic models of behavior. METHODS: Outpatients with hypertension from Austria,
      Belgium, England, Germany, Greece, Hungary, The Netherlands, Poland, and Wales
      were recruited to a cross-sectional online survey. Nonadherence to medicines was
      assessed using the Morisky Medication Adherence Scale (primary outcome) and the
      Medication Adherence Rating Scale. Associations with adherence and nonadherence
      were tested for demographic, clinical, and psychosocial factors. RESULTS: A total
      of 2595 patients completed the questionnaire. The percentage of patients classed
      as nonadherent ranged from 24% in The Netherlands to 70% in Hungary. Low age, low
      self-efficacy, and respondents' perceptions of their illness and cost-related
      barriers were associated with nonadherence measured on the Morisky Medication
      Adherence Scale across several countries. In multilevel, multivariate analysis,
      low self-efficacy (odds ratio = 0.73; 95% confidence interval 0.70-0.77) and a
      high number of perceived barriers to taking medicines (odds ratio = 1.70; 95%
      confidence interval 1.38-2.09) were the main significant determinants of
      nonadherence. Country differences explained 11% of the variance in nonadherence.
      CONCLUSIONS: Among the variables measured, patients' adherence to
      antihypertensive medicines is influenced primarily by their self-efficacy,
      illness beliefs, and perceived barriers. These should be targets for
      interventions for improving adherence, as should an appreciation of differences
      among the countries in which they are being delivered.

PMID- 25773558
TI  - Public preferences for prioritizing preventive and curative health care
      interventions: a discrete choice experiment.
AB  - BACKGROUND: Setting fair health care priorities counts among the most difficult
      ethical challenges our societies are facing. OBJECTIVE: To elicit through a
      discrete choice experiment the Belgian adult population's (18-75 years; N = 750)
      preferences for prioritizing health care and investigate whether these
      preferences are different for prevention versus cure. METHODS: We used a Bayesian
      D-efficient design with partial profiles, which enables considering a large
      number of attributes and interaction effects. We included the following
      attributes: 1) type of intervention (cure vs. prevention), 2) effectiveness, 3)
      risk of adverse effects, 4) severity of illness, 5) link between the illness and
      patient's health-related lifestyle, 6) time span between intervention and effect,
      and 7) patient's age group. RESULTS: All attributes were statistically
      significant contributors to the social value of a health care program, with
      patient's lifestyle and age being the most influential ones. Interaction effects
      were found, showing that prevention was preferred to cure for disease in young
      adults, as well as for severe and lethal disease in people of any age. However,
      substantial differences were found in the preferences of respondents from
      different age groups, with different lifestyles and different health states.
      CONCLUSIONS: Our study suggests that according to the Belgian public, contextual
      factors of health gains such as patient's age and health-related lifestyle should
      be considered in priority setting decisions. The studies, however, revealed
      substantial disagreement in opinion between different population subgroups.

PMID- 25773557
TI  - Learning and satisficing: an analysis of sequence effects in health valuation.
AB  - OBJECTIVE: To estimate the effect of sequence on response precision and response
      behavior in health valuation studies. METHODS: Time trade-off (TTO) and paired
      comparison responses from six health valuation studies-four US, one Spanish, and
      one Dutch-were examined (22,225 respondents) to test whether task sequence
      influences response precision (e.g., rounding), response changes, and median
      response times. Each study used a computer-based instrument that randomized task
      sequence among a national sample of adults, age 18 years or older, from the
      general population. RESULTS: For both TTO and paired comparisons, median response
      times decreased with sequence (i.e., learning), but tended to flatten after the
      first three tasks. Although the paired comparison evidence demonstrated that
      sequence had no effect on response precision, the frequency of rounded TTO
      responses (to either 1-year or 5-year units) increased with sequence.
      CONCLUSIONS: Based on these results, randomizing or reducing the number of paired
      comparison tasks does not appear to influence response precision; however,
      generalizability, practicality, and precautionary considerations remain. Overall,
      participants learned to respond efficiently within the first three tasks and did
      not resort to satisficing, but may have rounded their TTO responses.

PMID- 25773559
TI  - Critical appraisal of network meta-analyses evaluating the efficacy and safety of
      new oral anticoagulants in atrial fibrillation stroke prevention trials.
AB  - OBJECTIVES: To critically appraise published network meta-analyses (NMAs)
      evaluating the efficacy or safety of the new oral anticogulants (NOACs)
      dabigatran, rivaroxaban, and apixaban for the prevention of stroke in patients
      with nonvalvular atrial fibrillation (AF). METHODS: A systematic literature
      review was performed to identify the relevant NMAs using MEDLINE, EMBASE,
      Cochrane Library, Database of Abstracts of Reviews of Effects, and Health
      Technology Assessment. The synthesis studies were evaluated using the
      "Questionnaire to assess the relevance and credibility of the NMA." RESULTS:
      Eleven NMAs evaluating NOACs among adults with nonvalvular AF were identified.
      Most NMAs included three large phase III randomized controlled trials, comparing
      NOACs to adjusted-dose warfarin (Randomized Evaluation of Long-Term
      Anticoagulation Therapy [RE-LY], Rivaroxaban Once Daily Oral Direct Factor Xa
      Inhibition Compared With Vitamin K Antagonism for Prevention of Stroke and
      Embolism Trial in Atrial Fibrillation [ROCKET-AF], and Apixaban for Reduction of
      Stroke and Other Thromboembolic Events in Atrial Fibrillation [ARISTOTLE]). The
      main differences identified related to potential treatment effect modifiers
      regarding the mean time spent in therapeutic range (TTR) in the warfarin arm, the
      risk of stroke or systemic embolism across the trials (mean CHADS2 score: C =
      congestive heart failure, H = hypertension, A = older than age 75 years, D =
      diabetes mellitus, S2 = prior stroke or history of transient ischemic attack) or
      primary versus secondary prevention, and type of populations used in the
      analysis. Kansal et al. [Kansal AR, Sharma M, Bradley-Kennedy C, et al.
      Dabigatran versus rivaroxaban for the prevention of stroke and systemic embolism
      in atrial fibrillation in Canada: comparative efficacy and cost-effectiveness.
      Thromb Haemost 2012;108:672-82] appropriately adjusted the ROCKET-AF TTR to match
      the RE-LY population on the basis of individual patient data. Meta-regressions
      are not expected to minimize confounding bias given limited data, whereas
      subgroup analyses had some impact on the point estimates for the treatment
      comparisons. CONCLUSIONS: Results of the synthesis studies were generally
      comparable and suggested that the NOACs had similar efficacy, although some
      differences were identified depending on the outcome. The extent to which
      differences in the distribution of TTR, CHADS2 score, or primary versus secondary
      prevention biased the results remains unclear.

PMID- 25773560
TI  - A unified framework for classification of methods for benefit-risk assessment.
AB  - BACKGROUND: Patients, physicians, and other decision makers make implicit but
      inevitable trade-offs among risks and benefits of treatments. Many methods have
      been proposed to promote transparent and rigorous benefit-risk analysis (BRA).
      OBJECTIVE: To propose a framework for classifying BRA methods on the basis of key
      factors that matter most for patients by using a common mathematical notation and
      compare their results using a hypothetical example. METHODS: We classified the
      available BRA methods into three categories: 1) unweighted metrics, which use
      only probabilities of benefits and risks; 2) metrics that incorporate preference
      weights and that account for the impact and duration of benefits and risks; and
      3) metrics that incorporate weights based on decision makers' opinions. We used
      two hypothetical antiplatelet drugs (a and b) to compare the BRA methods within
      our proposed framework. RESULTS: Unweighted metrics include the number needed to
      treat and the number needed to harm. Metrics that incorporate preference weights
      include those that use maximum acceptable risk, those that use relative-value
      adjusted life-years, and those that use quality-adjusted life-years. Metrics that
      use decision makers' weights include the multicriteria decision analysis, the
      benefit-less-risk analysis, Boers' 3 by 3 table, the Gail/NCI method, and the
      transparent uniform risk benefit overview. Most BRA methods can be derived as a
      special case of a generalized formula in which some are mathematically identical.
      Numerical comparison of methods highlights potential differences in BRA results
      and their interpretation. CONCLUSIONS: The proposed framework provides a unified,
      patient-centered approach to BRA methods classification based on the types of
      weights that are used across existing methods, a key differentiating feature.

PMID- 25773561
TI  - Application of multicategory exposure marginal structural models to investigate
      the association between long-acting beta-agonists and prescribing of oral
      corticosteroids for asthma exacerbations in the Clinical Practice Research
      Datalink.
AB  - OBJECTIVE: To examine the comparative effectiveness of inhaled long-acting beta
      agonist (LABA), inhaled corticosteroid (ICS), and ICS/LABA combinations. METHODS:
      We used a retrospective cohort design of patients older than 12 years with asthma
      diagnosis in the Clinical Practice Research Datalink to evaluate asthma-related
      morbidity measured by oral corticosteroid (OCS) initiation within 12 months of
      initiating LABAs, ICSs, or ICSs/LABAs. Asthma severity 12 months before drug
      initiation (use of OCSs, asthma-related hospital or emergency department visits,
      and number of short-acting beta-agonist prescriptions) and during follow-up
      (short-acting beta-agonist prescriptions and total number of asthma drug classes)
      was adjusted as a time-varying variable via marginal structural models. RESULTS:
      A total of 51,103 patients with asthma were followed for 12 months after
      receiving first prescription for study drugs from 1993 to 2010. About 92%
      initiated ICSs, 1% initiated LABAs, and 7% initiated ICSs/LABAs. Compared with
      ICSs, LABAs were associated with a 10% increased risk of asthma exacerbations
      requiring short courses of OCSs (hazard ratio [HR] 1.10; 95% confidence interval
      [CI] 1.07-1.18). ICS/LABA initiators were 62% less likely than ICS initiators (HR
      0.38; 95% CI 0.12-0.66) and 50% less likely than LABA initiators to receive OCS
      prescriptions for asthma exacerbations (HR 0.50; 95% CI 0.14-0.78). CONCLUSIONS:
      In concordance with current asthma management guidelines, inhaled LABAs should
      not be prescribed as monotherapy to patients with asthma. The findings suggest
      the presence of time-dependent confounding by asthma severity, which was
      accounted for by the marginal structural model.

PMID- 25773562
TI  - The changing face of the cost-utility literature, 1990-2012.
AB  - OBJECTIVES: Cost-utility analyses (CUAs) have been published widely over the
      years to measure the value of health care interventions. We investigated the
      growth and characteristics of CUAs in the peer-reviewed English-language
      literature through 2012. METHODS: We analyzed data from the Tufts Medical Center
      Cost-Effectiveness Analysis (CEA) Registry, a database containing more than 3700
      English-language CUAs published through 2012. We summarized various study
      characteristics (e.g., intervention type, funding source, and journal of
      publication) and methodological practices (e.g., use of probabilistic sensitivity
      analysis) over three time periods: 1990 to 1999, 2000 to 2009, and 2010 to 2012.
      We also examined CUAs by country, region, and the degree to which diseases
      studied correlate with disease burden. RESULTS: The number of published CUAs rose
      from 34 per year from 1990 to 1999 to 431 per year from 2010 to 2012. The
      proportion of studies focused on the United States declined from 61% during 1990
      to 1999 to 35% during 2010 to 2012 (P < 0.0001). Although still small compared
      with CUAs in higher income countries, the number of CUAs focused on lower and
      middle-income countries has risen sharply. A large fraction of studies pertain to
      pharmaceuticals (46% during 2010-2012). In recent years, most studies included
      probabilistic sensitivity analysis (67% during 2010-2012). Journals publishing
      CUAs vary widely in the percentage of their studies funded by drug companies.
      Some conditions, such as injuries, have high burden but few CUAs. CONCLUSIONS:
      Our review reveals considerable growth and some change in the cost-utility
      literature in recent years. The data suggest growing interest in cost-utility
      methodology, particularly in non-Western countries.

PMID- 25773563
TI  - Fairness versus efficiency of vaccine allocation strategies.
AB  - OBJECTIVES: To develop a framework to objectively measure the degree of fairness
      of any allocation rule aimed at distributing a limited stockpile of vaccines to
      contain the spread of influenza. METHODS: The trade-off between the efficiency
      and fairness of allocation strategies was demonstrated through an illustrative
      simulation study of an influenza epidemic in Southwestern Virginia. A Susceptible
      Exposed-Infectious-Recovered model was used to represent the disease progression
      within the host. RESULTS: Our findings showed that among all the criteria
      considered here, the household size (largest first) combined with age (youngest
      first)-based strategy leads to the best outcome. At 80% fairness, highest
      efficiency can be achieved but in order to be 100% fair, disease prevalence will
      have to rise by approximately 1.5%. CONCLUSIONS: This research provides a
      framework to objectively determine the degree of fairness of vaccine allocation
      strategies.

PMID- 25773564
TI  - Which factors enhance positive drug reimbursement recommendation in Scotland? A
      retrospective analysis 2006-2013.
AB  - OBJECTIVES: To identify the factors that influence the Scottish Medicines
      Consortium (SMC) in deciding whether to accept pharmaceutical technologies for
      use within the Scottish health care system. METHODS: A database of SMC
      submissions between 2006 and 2013 was created, containing a range of clinical,
      economic, and other factors extracted from published health technology assessment
      reports. A binomial outcome variable was used, defined as the decision to "accept
      for use" or "not recommend" a technology. Univariate and multivariate analyses
      were conducted to assess the impact by means of odds ratios (ORs) of the
      submitted evidence on the recommendation decision. RESULTS: Out of 463
      applications, 265 were accepted for use (57%) and 198 (43%) were not recommended
      for use within National Health Service Scotland. Univariate analyses showed that
      13 variables significantly affected the SMC decision. Of these 13 variables, 7
      variables were shown to have a meaningful impact in the multivariate analysis.
      Four of these concerned the outcome of cost-effectiveness analyses; the fact that
      a submission was supported by a cost-minimization analysis was the strongest
      positive variable (OR = 10.30) and a submission showing a product not being cost
      effective (i.e., incremental cost-effectiveness ratio above L30,000/quality
      adjusted life-year gained) was the strongest negative predictor (OR = 0.47). The
      other variables concerned whether the submission was related to a product
      indicated for a nervous system disease (OR = 0.41), whether it was indicated for
      nonchronic use (OR = 1.66), and whether the submission was performed by a big
      company (OR = 2.83). CONCLUSIONS: This study demonstrated that the outcome of
      cost-effectiveness analyses is an important factor affecting the SMC's
      reimbursement recommendation decision.

PMID- 25773565
TI  - Implications of the minimal clinically important difference for health-related
      quality-of-life outcomes: a comparison of sample size requirements for an
      incontinence treatment trial.
AB  - BACKGROUND: Sample size calculations for treatment trials that aim to assess
      health-related quality-of-life (HRQOL) outcomes are often difficult to perform.
      Researchers must select a target minimal clinically important difference (MCID)
      in HRQOL for the trial, estimate the effect size of the intervention, and then
      consider the responsiveness of different HRQOL measures for detecting
      improvements. Generic preference-based HRQOL measures are usually less sensitive
      to gains in HRQOL than are disease-specific measures, but are nonetheless
      recommended to quantify an impact on HRQOL that can be translated into quality
      adjusted life-years during cost-effectiveness analyses. Mapping disease-specific
      measures onto generic measures is a proposed method for yielding more efficient
      sample size requirements while retaining the ability to generate utility weights
      for cost-effectiveness analyses. OBJECTIVES: This study sought to test this
      mapping strategy to calculate and compare the effect on sample size of three
      different methods. METHODS: Three different methods were used for determining an
      MCID in HRQOL in patients with incontinence: 1) a global rating of improvement,
      2) an incontinence-specific HRQOL instrument, and 3) a generic preference-based
      HRQOL instrument using mapping coefficients. RESULTS: The sample size required to
      detect a 20% difference in the MCID for the global rating of improvement was 52
      per trial arm, 172 per arm for the incontinence-specific HRQOL outcome, and 500
      per arm for the generic preference-based HRQOL outcome. CONCLUSIONS: We caution
      that treatment trials of conditions for which improvements are not easy to
      measure on generic HRQOL instruments will still require significantly greater
      sample size even when mapping functions are used to try to gain efficiency.

PMID- 25773566
TI  - Mapping the clinical chronic obstructive pulmonary disease questionnaire onto
      generic preference-based EQ-5D values.
AB  - OBJECTIVES: To develop a model to predict EuroQol five-dimensional questionnaire
      (EQ-5D) values from clinical chronic obstructive pulmonary disease (COPD)
      questionnaire (CCQ) scores. METHODS: We used data from three clinical trials (the
      Randomized Clinical Trial on Effectiveness of Integrated COPD Management in
      Primary Care [RECODE], the Assessment Of Going Home Under Early Assisted
      Discharge [GO-AHEAD], and the Health Status Guided COPD Care [MARCH]). Data were
      randomly split into an estimation sample and a validation sample. The conceptual
      similarity between patient-reported CCQ and preference-based EQ-5D scores was
      assessed using correlation and principal-component analysis. Different types of
      models were estimated with increasing complexity. We selected the final models on
      the basis of mean absolute error and root mean square error when comparing
      predicted and observed values from the same population (internal validity) and
      from different trial populations (external validity). We also developed models
      for different country-specific EQ-5D value sets. RESULTS: The principal-component
      analysis showed that the CCQ domains functional state and mental state are
      associated with four dimensions of the EQ-5D. The EQ-5D dimension pain/discomfort
      formed a separate construct on which no CCQ item loaded. The mean observed EQ-5D
      values were not significantly different from the mean predicted EQ-5D values in
      internal validation samples but did significantly differ in external validation
      samples. The models underestimated EQ-5D values in milder health states and
      overestimated them in more severe health states. The predictive ability of the
      models was similar across different EQ-5D value sets. CONCLUSIONS: The models can
      predict mean EQ-5D values that are similar to observed mean values in a similar
      population. The overestimating/underestimating of the low/high EQ-5D values,
      however, limits its use in Markov models. Therefore, mapping should be used
      cautiously.

PMID- 25773567
TI  - Cost-utility analyses in diabetes: a systematic review and implications from real
      world evidence.
AB  - OBJECTIVES: To systematically review the cost-effectiveness of diabetes
      interventions, identify high-value diabetes services, and estimate potential
      gains from increasing their utilization. METHODS: The study consisted of two
      steps. First, we reviewed cost-utility analyses (CUAs) related to diabetes
      published through the end of 2012, using the Tufts Medical Center Cost
      Effectiveness Analysis Registry (www.cearegistry.org). We used logistic
      regression to examine factors independently associated with favorable cost
      effective ratios. Second, we used the Humedica electronic medical records to
      estimate potential savings and health benefits gained by shifting patients
      currently receiving low-value services to high-value alternatives. RESULTS: We
      identified 196 diabetes CUAs, of which 55% examined pharmaceuticals. Most (70%)
      diabetes CUAs focused on treatment rather than prevention. Most used a health
      care payer perspective and were industry-sponsored. Of the 497 published cost
      utility ratios, 82% examined an intervention recommended by diabetes guidelines.
      Approximately 73% of the interventions were cost-saving or below $50,000 per
      quality-adjusted life-year. Logistic regression analysis showed that higher
      quality CUAs, CUAs conducted from the US perspective, surgical interventions, and
      guideline-recommended interventions were more likely to report favorable ratios.
      Of the 7907 eligible patients with diabetes in our sample, up to 7117 could in
      principle be shifted to cost-saving treatments, reducing costs by $12.5 million
      and gaining more than 1938 quality-adjusted life-years over a lifetime.
      CONCLUSIONS: Most diabetes interventions evaluated by CUAs are recommended by
      practice guidelines and may provide good value for money. Our results indicate
      that patients with diabetes and the health care system could potentially benefit
      from shifting to the greater use of high-value services.

PMID- 25773568
TI  - A systematic review of generic multidimensional patient-reported outcome measures
      for children, part I: descriptive characteristics.
AB  - OBJECTIVES: To identify generic, multidimensional patient-reported outcome
      measures (PROMs) for children up to 18 years old and describe their
      characteristics and content assessed using the International Classification of
      Functioning, Disability and Health Children and Youth version (ICF-CY). METHODS:
      The search strategy, developed by an information specialist, included four groups
      of terms related to "measure," "health," "children and young people," and
      "psychometric performance." The search was limited to publications from 1992.
      Five electronic databases and two online-specific PROM databases were searched.
      Two groups of reviewers independently screened all abstracts for eligible PROMs.
      Descriptive characteristics of the eligible PROMs were collected, and items and
      domains of each questionnaire were mapped onto the ICF-CY chapters. RESULTS: We
      identified 35 PROMs, of which 29 were generic PROMs and 6 were preference-based
      measures. Many PROMs cover a range of aspects of health; however, social
      functioning is represented most often. Content covered differs both in which
      aspects of health are assessed and whether individual questions focus on
      functioning (what the subject can or does do) and/or well-being (how the subject
      feels about a certain aspect of his or her health). CONCLUSIONS: A broad variety
      of PROMs is available to assess children's health. Nevertheless, only a few PROMs
      can be used across all age ranges to 18 years. When mapping their content on the
      ICF-CY, it seems that most PROMs exclude at least one major domain, and all
      conflate aspects of functioning and well-being in the scales.

PMID- 25773569
TI  - A systematic review of generic multidimensional patient-reported outcome measures
      for children, part II: evaluation of psychometric performance of English-language
      versions in a general population.
AB  - OBJECTIVES: The objectives of this systematic review were 1) to identify studies
      that assess the psychometric performance of the English-language version of 35
      generic multidimensional patient-reported outcome measures (PROMs) for children
      and young people in general populations and evaluate their quality and 2) to
      summarize the psychometric properties of each PROM. METHODS: MEDLINE, EMBASE, and
      PsycINFO were searched. The methodological quality of the articles was assessed
      using the COnsensus-based Standards for selection of health Measurement
      INstruments checklist. For each PROM, extracted evidence of content validity,
      construct validity, internal consistency, test-retest reliability, proxy
      reliability, responsiveness, and precision was judged against standardized
      reference criteria. RESULTS: We found no evidence for 14 PROMs. For the remaining
      21 PROMs, 90 studies were identified. The methodological quality of most studies
      was fair. Quality was generally rated higher in more recent studies. Not
      reporting how missing data were handled was the most common reason for
      downgrading the quality. None of the 21 PROMs has had all psychometric properties
      evaluated; data on construct validity and internal consistency were most
      frequently reported. CONCLUSIONS: Overall, consistent positive findings for at
      least five psychometric properties were found for Child Health and Illness
      Profile, Healthy Pathways, KIDSCREEN, and Multi-dimensional Student Life
      Satisfaction Scale. None of the PROMs had been evaluated for responsiveness to
      detect change in general populations. Further well-designed studies with
      transparent reporting of methods and results are required.

PMID- 25773570
TI  - Need for multicriteria evaluation of generic drug policies.
AB  - Policymakers tend to focus on improving patented drug policies because they are
      under pressure from patients, physicians, and manufacturers to increase access to
      novel therapies. The success of pharmaceutical innovation over the last few
      decades has led to the availability of many off-patent drugs to treat disease
      areas with the greatest public health need. Therefore, the success of public
      health programs in improving the health status of the total population is highly
      dependent on the efficiency of generic drug policies. The objective of this
      article was to explore factors influencing the true efficiency of generic
      prescription drug policies in supporting public health initiatives in the
      developed world. Health care decision makers often assess the efficiency of
      generic drug policies by the level of price erosion and market share of generics.
      Drug quality, bioequivalence, in some cases drug formulations, supply
      reliability, medical adherence and persistence, health outcomes, and nondrug
      costs, however, are also attributes of success for generic drug policies. Further
      methodological research is needed to measure and improve the efficiency of
      generic drug policies. This also requires extension of the evidence base of the
      impact of generic drugs, partly based on real-world evidence. Multicriteria
      decision analysis may assist policymakers and researchers to evaluate the true
      value of generic drugs. 

PMID- 25773571
TI  - Do the current performance-based schemes in Italy really work? "Success fee": a
      novel measure for cost-containment of drug expenditure.

PMID- 25773572
TI  - Common variable immunodeficiency and pulmonary amyloidosis: a case report.
AB  - Common variable immunodeficiency is the most common symptomatic primary immune
      deficiency characterized by hypogammaglobulinemia, recurrent infections, and
      increased risk of autoimmune disease and malignancy. Secondary amyloidosis
      develops from chronic inflammatory conditions. The co-existence of CVID
      (especially in patients with bronchiectasis) and secondary amyloidosis has been
      reported rarely. We describe the first case of pulmonary hypertension secondary
      to pulmonary amyloidosis in a patient with CVID. 

PMID- 25773573
TI  - Enhanced performance of PbS-sensitized solar cells via controlled successive
      ionic-layer adsorption and reaction.
AB  - Despite the potential of PbS quantum dots (QDs) as sensitizers for quantum-dot
      sensitized solar cells (QDSSCs), achieving a high photocurrent density over 30 mA
      cm(-2) remains a challenging task in PbS-sensitized solar cells. In contrast to
      previous attempts, where Hg(2+)-doping or multi-step post-treatment is necessary,
      we are capable of achieving a high photocurrent exceeding 30 mA cm(-2) simply by
      manipulating the successive ionic layer adsorption and reaction (SILAR) method.
      We show that controlling temperature at which SILAR is performed is critical to
      obtain a higher and more uniform coverage of PbS QDs over a mesoporous TiO2 film.
      The deposition of a CdS inter-layer between TiO2 and PbS is found to be an
      effective means of ensuring high photocurrent and stability. Not only does this
      modification improve the light absorption capability of the photoanode, but it
      also has a significant effect on charge recombination and electron injection
      efficiency at the PbS/TiO2 interface according to our in-depth study using
      electrochemical impedance spectroscopy (EIS). The implication of subtle changes
      in the interfacial events via modified SILAR conditions for PbS-sensitized solar
      cells is discussed. 

PMID- 25773574
TI  - Copper-catalyzed aerobic oxidative cleavage of C-C bonds in epoxides leading to
      aryl nitriles and aryl aldehydes.
AB  - Novel copper-catalyzed aerobic synthesis of aryl nitriles and aldehydes from
      epoxides via C-C single bond cleavage has been discovered. This reaction provides
      a practical method toward the synthesis of aryl nitriles and aldehydes, which are
      versatile intermediates and building blocks in organic synthesis. 

PMID- 25773575
TI  - Comparing the long-term results of two uncemented femoral stems for total hip
      arthroplasty.
AB  - 327 proximal and 185 extensively coated femoral stems with mean 10-year follow-up
      were reviewed. Implant survivorship, clinical outcomes, and radiographic analyses
      were compared. Kaplan-Meier implant survivorship was 97.5% for the proximal, and
      98.8% for the extensively coated stem for stem-only revisions at 10-years. The
      proximally coated stem outperformed on the PCS arm of the SF-12 (P = 0.04) and
      stiffness arm of the WOMAC (P = 0.03). Otherwise, all clinical outcomes were
      comparable. Thigh pain incidence was 12.5% and 5.3% for the extensive versus
      proximally coated groups, respectively (P = 0.007). Radiographic review
      identified more severe stress shielding (P < 0.001) in the extensively coated
      stems. This study supports the long-term clinical track record of total hip
      arthroplasty using two different cementless stem designs.

PMID- 25773576
TI  - Effect of Taper Design on Trunnionosis in Metal on Polyethylene Total Hip
      Arthroplasty.
AB  - This study examines how taper design affects corrosion and fretting at the head
      trunnion surface. All hip prostheses retrieved between 1999 and 2013 with 28mm/+0
      heads were selected, resulting in 44 cobalt-chrome-on-polyethylene implants,
      representing six taper designs. Mean implantation time: 8.9+/-3.7years. The
      femoral head tapers were scored for fretting and corrosion using the Goldberg
      scale as both a combined score and by three zones (apex, central and base). There
      was no difference in age (P=0.34), BMI (P=0.29), or implantation time (P=0.19)
      between taper groups. The 11/13 taper had the highest combined corrosion and
      fretting score, but no difference (P=0.22) between groups for combined scores
      (P=0.22 for corrosion, P=0.19 for fretting). In a zone-specific analysis, the
      11/13 taper had highest corrosion score at base zone (P=0.02). Taper design had a
      significant effect on corrosion at base of trunnion. 

PMID- 25773577
TI  - Gender-based health interventions in the United States: An overview of the
      coalition for healthier community initiative.
AB  - Health disparities by gender constitute an important yet often overlooked aspect
      of health around the globe. Within the United States, there is both a paucity of
      research as well as planned programs that take into account how socio-cultural
      roles and expectations for men and women may differentially affect symptoms,
      access to care, and treatment. Viewing women's health exclusively as a function
      of sex (i.e., biological) differences represents a narrow understanding that does
      not fully explain gaps in health disparities between men and women. In September
      2010, the U.S. Department of Health and Human Services (DHHS) launched a national
      initiative entitled the Coalition for a Healthier Community (CHC) to employ a
      gender-based framework in several urban, suburban and rural communities across
      the nation. The Office on Women's Health (OWH) within the DHHS funded 10
      coalitions to ultimately improve the health of women and girls utilizing a gender
      based approach. This article provides an overview of the initiative and the focus
      of the special issue. 

PMID- 25773578
TI  - Structure-5-HT receptor affinity relationship in a new group of 7
      arylpiperazynylalkyl and 7-tetrahydroisoquinolinylalkyl derivatives of 8-amino
      1,3-dimethyl-1H-purine-2,6(3H,7H)-dione.
AB  - In our previous paper, we have reported that some 8-alkoxy-1,3-dimethyl-1H-purine
      2,6(3H,7H)-dione derivatives possessed high affinity and displayed agonistic
      activity for the serotonin 5-HT1A receptor. In order to examine the influence of
      the substituent in the position 8 of the purine moiety on the affinity for the
      serotonin 5-HT1A , 5-HT2A , and 5-HT7 receptors, a series of 7
      arylpiperazynylalkyl and 7-tetrahydroisoquinolinylalkyl (THIQ) derivatives of 8
      amino-1,3-dimethyl-1H-purine-2,6(3H,7H)-dione were synthesized. All the final
      compounds were investigated in in vitro competition binding experiments for
      serotonin 5-HT1A , 5-HT2A , and 5-HT7 receptors. The structure-affinity
      relationships for this group of compounds were discussed. For selected compounds,
      functional assays for the 5-HT1A receptor were carried out. The results of the
      assays indicated that these groups of derivatives possessed antagonistic activity
      for this receptor.

PMID- 25773579
TI  - Changing clinical guidelines from delayed to early aperient administration for
      enterally fed intensive care patients was associated with increased diarrhoea: a
      before-and-after, intention-to-treat evaluation.
AB  - BACKGROUND: The 14-bed intensive care unit of a tertiary referral hospital
      adopted a guideline to start docusate sodium with sennosides when enteral
      nutrition was started. This replaced a guideline to start aperients after 24h of
      enteral nutrition if no bowel action had occurred. We sought to determine the
      effect of this change on the incidence of diarrhoea and constipation in intensive
      care. METHODS: Retrospective audit of the medical records of consecutive adult
      patients admitted to intensive care and given enteral nutrition, excluding those
      with a primary gastrointestinal system diagnosis, between Jan-Aug 2011 (the
      delayed group, n=175) and Jan-Aug 2012 (the early group, n=175). The early
      aperient guideline was implemented during Sep-Dec 2011. RESULTS: The early and
      delayed groups were similar in age (median 62 years vs. 64 years; P=0.17), sex
      (males 65% vs. 63%; P=0.91), and postoperative cases (31% vs. 33%; P=0.82) and
      had similar proportions who received mechanical ventilation (95% vs. 95%;
      P=1.00), an inotrope or vasopressor (63% vs. 70%; P=0.17), renal replacement
      therapy (8% vs. 10%; P=0.71), opiates (77% vs. 80%; P=0.60), antibiotics (89% vs.
      91%; P=0.72) and metoclopramide (46% vs. 55%; P=0.11). A significantly larger
      proportion of the early group received an aperient (54% vs. 29%, P<0.001) and
      experienced diarrhoea (38% vs. 27%, P=0.04), but the groups had similar
      proportions affected by constipation (42% vs. 43%, P=0.91). CONCLUSIONS: Changing
      guidelines from delayed to early aperient administration was associated with an
      increase in the incidence of diarrhoea but was not associated with the incidence
      of constipation. These findings do not support changing guidelines from delayed
      to early aperient administration.

PMID- 25773580
TI  - Association of Hematocrit and Red Blood Cell Transfusion with Outcomes in Infants
      Undergoing Norwood Operation.
AB  - The objective of this study was to investigate the association between red blood
      cell (RBC) transfusion and hematocrit values with outcomes in infants undergoing
      Norwood operation. This study included infants <=2 months of age who underwent
      Norwood operation with either a modified Blalock-Taussig shunt or a right
      ventricle-pulmonary artery shunt. Demographics, preoperative, operative, daily
      laboratory data, and postoperative variables were collected. The primary outcome
      measures evaluated included mortality, ICU length of stay, length of mechanical
      ventilation, and days to chest closure. The secondary outcome measures evaluated
      included lactate levels, estimated glomerular filtration rate, and inotrope score
      in the first 14 days after heart operation. Cox proportional hazard models were
      fitted to study the probability of study outcomes as a function of hematocrit
      values and RBC transfusions after operation. Eighty-nine patients qualified for
      inclusion. With a median hematocrit of 46 (IQR 44, 49), and a median RBC
      transfusion of 92 ml/kg (IQR 31, 384) in the first 14 days after operation, 81
      (91 %) patients received RBC transfusions. A multivariable analysis adjusted for
      risk factors, including the age, weight, prematurity, cardiopulmonary bypass and
      cross-clamp time, and postoperative need for nitric oxide and dialysis,
      demonstrated no association between hematocrit and RBC transfusion with majority
      of study outcomes. This single-center study found that higher hematocrit values
      and increasing RBC transfusions are not associated with improved outcomes in
      infants undergoing Norwood operation.

PMID- 25773581
TI  - Changes in Plasma Atrial and Brain Natriuretic Peptide Levels in Children
      Undergoing Surgical Isolated Atrial Septal Defect Closure.
AB  - Plasma atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP)
      levels increase after cardiopulmonary bypass (CPB) in pediatric patients.
      However, the exact reason for the postoperative increase remains unclear. This
      study elucidated the perioperative changes in plasma natriuretic peptide levels
      in children undergoing surgical isolated atrial septal defect (ASD) closure.
      Between 2010 and 2012, 24 pediatric patients (median 7.1, range 2.7-15.7 years)
      underwent surgery for simple ASD using CPB under ventricular fibrillation (Group
      A, 16 patients) or under cardiac arrest (Group B, 8 patients). Natriuretic
      peptide levels were measured before surgery, on postoperative day 0, 1, 3, and at
      the first outpatient visit. The pulmonary to systemic blood flow ratio (Qp/Qs)
      was estimated by echocardiography using an index of right ventricle end-diastolic
      area. Preoperative natriuretic peptide levels positively correlated with the
      Qp/Qs. Plasma ANP levels peaked on postoperative day 0, and its values were
      higher in Group A than in Group B patients (p < 0.001). Plasma BNP levels
      increased significantly in both Groups on postoperative day 1, and its values
      were significantly greater in Group A than in Group B patients (p = 0.007). There
      was a weak negative correlation between the amount of postoperative increase in
      natriuretic peptide levels and the Qp/Qs. There was no appreciable difference in
      the acute postoperative clinical course and echocardiographic parameter on
      postoperative day 3 between Group A and B patients. In conclusion, acute
      postoperative natriuretic peptide levels after isolated ASD closure were
      multifactorial, and they might be unreliable for predicting clinical outcomes.

PMID- 25773582
TI  - Anisotropy-Guided Enantiomeric Enhancement in Alanine Using Far-UV Circularly
      Polarized Light.
AB  - All life on Earth is characterized by its asymmetry - both the genetic material
      and proteins are composed of homochiral monomers. Understanding how this
      molecular asymmetry initially arose is a key question related to the origins of
      life. Cometary ice simulations, L-enantiomeric enriched amino acids in meteorites
      and the detection of circularly polarized electromagnetic radiation in star
      forming regions point to a possible interstellar/protostellar generation of
      stereochemical asymmetry. Based upon our recently recorded anisotropy spectra
      g(lambda) of amino acids in the vacuum-UV range, we subjected amorphous films of
      racemic (13)C-alanine to far-UV circularly polarized synchrotron radiation to
      probe the asymmetric photon-molecule interaction under interstellar conditions.
      Optical purities of up to 4% were reached, which correlate with our theoretical
      predictions. Importantly, we show that chiral symmetry breaking using circularly
      polarized light is dependent on both the helicity and the wavelength of incident
      light. In order to predict such stereocontrol, time-dependent density functional
      theory was used to calculate anisotropy spectra. The calculated anisotropy
      spectra show good agreement with the experimental ones. The European Space
      Agency's Rosetta mission, which successfully landed Philae on comet 67P/Churyumov
      Gerasimenko on 12 November 2014, will investigate the configuration of chiral
      compounds and thereby obtain data that are to be interpreted in the context of
      the results presented here.

PMID- 25773583
TI  - The Self-Referential Genetic Code is Biologic and Includes the Error Minimization
      Property.
AB  - The distribution of the triplet to amino acid correspondences in the genetic code
      matrix contains blocks of similarity. There are (a) groups of similar triplets
      coding for the same amino acid, which is called code degeneracy, and (b) clusters
      of similar amino acids corresponding to similar triplets. Processes that led to
      this regionalization have been investigated through a variety of perspectives but
      no consensus has been reached and no model has been convincing enough to drive
      experimental tests. Most traditional has been the hypothesis that the code was
      derived from the standard evolutionary processes of testing variations in the
      correspondences through the fitness measure of reaching distributions in the
      matrix space in an optimal manner so that the effects of mutations on protein
      phenotypes would be minimized, that is, with reduction of the intensity or of the
      deviant quality of the functional alterations associated with variations. In
      contrast, the self-referential model for the formation of the code is based on an
      original regionalization of characters through the concerted superposition of the
      two components of the encodings: the four modules of dimers of tRNAs are occupied
      sequentially by sets of amino acids that are also sequentially devoted to
      fulfilling specific functions in the protein sites and motifs to which they
      preferentially belong. Therewith, part (b) of the error-minimizing property
      follows. Part (a) of the property, the code degeneracy, is derived from the
      synthetase character of developing specificities directed initially to the
      principal dinucleotides of the triplets, resulting in tetracodonic degeneracy.
      This was later partly modified during evolution according to the developments of
      codon usage and the introduction of new amino acids. 

PMID- 25773584
TI  - Phosphorus: a case for mineral-organic reactions in prebiotic chemistry.
AB  - The ubiquity of phosphorus (P) in modern biochemistry suggests that P may have
      participated in prebiotic chemistry prior to the emergence of life. Of the major
      biogenic elements, phosphorus alone lacks a substantial volatile phase and its
      ultimate source therefore had to have been a mineral. However, as most native P
      minerals are chemically un-reactive within the temperature-pressure-pH regimes of
      contemporary life, it begs the question as to whether the most primitive early
      living systems on earth had access to a more chemically reactive P-mineral
      inventory. The meteoritic mineral schreibersite has been proposed as an important
      source of reactive P on the early earth. The chemistry of schreibersite as a P
      source is summarized and reviewed here. Recent work has also shown that reduced
      oxidation state P compounds were present on the early earth; these compounds lend
      credence to the relevance of schreibersite as a prebiotic mineral. Ultimately,
      schreibersite will oxidize to phosphate, but several high-energy P intermediates
      may have provided the reactive material necessary for incorporating P into
      prebiotic molecules. 

PMID- 25773585
TI  - On the biogenic origins of homochirality.
AB  - Homochirality, the single-handedness of optically asymmetric chemical structures,
      is present in all major biological macromolecules. Terrestrial life's preference
      for one isomer over its mirror image in D-sugars and L-amino acids has both
      fascinated and puzzled biochemists for over a century. But the contrasting case
      of the equally fundamental phospholipids has received less attention. Although
      the phospholipid glycerol headgroups of archaea and bacteria are both exclusively
      homochiral, the stereochemistries between the two domains are opposite. Here I
      argue that the reason for this "dual homochirality" was a simple evolutionary
      choice at the independent origin of the two synthesizing enzymes. More broadly,
      this points to a trivial biogenic cause for the evolution of homochirality: the
      enzymatic processes that produce chiral biomolecules are stereospecific in
      nature. Once an orientation has been favored, shifting to the opposite is both
      difficult and unnecessary. Homochirality is thus the simplest and most
      parsimonious evolutionary case. 

PMID- 25773587
TI  - A Ag-molecularly imprinted polymer composite for efficient surface-enhanced Raman
      scattering activities under a low-energy laser.
AB  - In this work, we have fabricated flower-shaped Ag particles coated with a
      molecularly imprinted polymer (Ag@MIP) based on the molecular imprinting
      technique and SERS technology. Although Raman signals decrease with the reducing
      laser power, Ag@MIP could sensitively detect the target molecules even at a laser
      power as low as 0.14 MUW. As a new SERS substrate, Ag@MIP shows high enhancement
      under low irradiation effectively, which limits the possible laser induced
      effects in the measurement process, improving the signal-to-noise ratio and
      repeatability. This platform has potential for the development of next-generation
      SERS spectroscopy. 

PMID- 25773586
TI  - Treatment of compensatory hyperhidrosis after sympathectomy with botulinum toxin
      and anticholinergics.
AB  - PURPOSE: Compensatory hyperhidrosis (CH) is the most common adverse complication
      of sympathectomy. It often has a major negative impact on life quality. No
      efficient treatment of CH is available. We report nine cases of CH after
      sympathectomy, which were treated with botulinum toxin A/B (BTX) and
      anticholinergics. METHODS: The patients responded to a dermatology life quality
      index (DLQI) questionnaire before injections with BTX and 3 weeks after
      treatment. At the follow-up visit, the participants also ranked the effect of the
      treatment on a five-grade scale. Three patients had residual sweating after BTX
      treatment, and received additional anticholinergics at the follow-up visit. Those
      subjects eventually had a third evaluation with the DLQI. RESULTS: The DLQI score
      was, on average, 16.4 before treatment and decreased to 4.8 after BTX injections.
      Eight out of nine patients were satisfied with the treatment. The average DLQI
      score decreased to 2.2 when the patients with residual sweating (n = 3) received
      additional anticholinergics. Adverse events from BTX were mild and temporary, but
      dry mouth was substantial in one patient using anticholinergics. CONCLUSIONS: A
      combination of BTX A/B and anticholinergics alleviated the hyperhidrosis with
      minor side-effects. We consider this treatment safe, effective, and well
      tolerated.

PMID- 25773588
TI  - Transition from fetal to neonatal circulation: Modeling the effect of umbilical
      cord clamping.
AB  - Hemodynamics of the fetal to neonatal transition are orchestrated through complex
      physiological changes and results in cardiovascular adaptation to the adult
      biventricular circulation. Clinical practice during this critical period can
      influence vital organ physiology for normal newborns, premature babies and
      congenital heart defect patients. Particularly, the timing of the cord clamping
      procedure, immediate (ICC) vs. delayed cord clamping (DCC), is hypothesized to be
      an important factor for the transitory fetal hemodynamics. The clinical need for
      a quantitative understanding of this physiology motivated the development of a
      lumped parameter model (LPM) of the fetal cardio-respiratory system covering the
      late-gestation to neonatal period. The LPM was validated with in vivo clinical
      data and then used to predict the effects of cord clamping procedures on
      hemodynamics and vital gases. Clinical time-dependent resistance functions to
      simulate the vascular changes were introduced. For DCC, placental transfusion
      (31.3 ml) increased neonatal blood volume by 11.7%. This increased blood volume
      is reflected in an increase in preload pressures by ~20% compared to ICC, which
      in turn increased the cardiac output (CO) by 20% (COICC=993 ml/min; CODCC=1197
      ml/min). Our model accurately predicted dynamic flow patterns in vivo. DCC was
      shown to maintain oxygenation if the onset of pulmonary respiration was delayed
      or impaired. On the other hand, a significant 25% decrease in oxygen saturations
      was observed when applying ICC under the same physiological conditions. We
      conclude that DCC has a significant impact on newborn hemodynamics, mainly
      because of the improved blood volume and the sustained placental respiration.

PMID- 25773589
TI  - Examining the response pressure along a fluid-filled elastic tube to comprehend
      Frank's arterial resonance model.
AB  - Frank first proposed the arterial resonance in 1899. Arteries are blood-filled
      elastic vessels, but resonance phenomena for a fluid-filled elastic tube has not
      drawn much attention yet. In this study, we measured the pressure along long
      elastic tubes in response to either a single impulsive water ejection or a
      periodic water input. The experimental results showed the low damped pressure
      oscillation initiated by a single impulsive water input; and the natural
      frequencies of the tube, identified by the peaks of the response in the frequency
      domain, were inversely proportional to the length of the tube. We found that the
      response to the periodic input reached a steady distributed oscillation with the
      same period of the input after a short transient time; and the optimal pressure
      response, or resonance, occurred when the pumping frequency was near the
      fundamental natural frequency of the system. We pointed out that the distributed
      forced oscillation could also be a suitable approach to analyze the arterial
      pressure wave. Unlike Frank's resonance model in which the whole arterial system
      was lumped together to a simple 0-D oscillator and got only one natural
      frequency, a tube has more than one natural frequency because the pressure P(z,t)
      is a 1-D oscillatory function of the axial position z and the time t. The benefit
      of having more than one natural frequency was then discussed.

PMID- 25773590
TI  - Biomechanical analyses of stair-climbing while dual-tasking.
AB  - Stair-climbing while doing a concurrent task like talking or holding an object is
      a common activity of daily living which poses high risk for falls. While
      biomechanical analyses of overground walking during dual-tasking have been
      studied extensively, little is known on the biomechanics of stair-climbing while
      dual-tasking. We sought to determine the impact of performing a concurrent
      cognitive or motor task during stair-climbing. We hypothesized that a concurrent
      cognitive task will have a greater impact on stair climbing performance compared
      to a concurrent motor task and that this impact will be greater on a higher-level
      step. Ten healthy young adults performed 10 trials of stair-climbing each under
      four conditions: stair ascending only, stair ascending and performing subtraction
      of serial sevens from a three-digit number, stair ascending and carrying an empty
      opaque box and stair ascending, performing subtraction of serial sevens from a
      random three-digit number and carrying an empty opaque box. Kinematics (lower
      extremity joint angles and minimum toe clearance) and kinetics (ground reaction
      forces and joint moments and powers) data were collected. We found that a
      concurrent cognitive task impacted kinetics but not kinematics of stair-climbing.
      The effect of dual-tasking during stair ascent also seemed to vary based on the
      different phases of stair ascent stance and seem to have greater impact as one
      climbs higher. Overall, the results of the current study suggest that the
      association between the executive functioning and motor task (like gait) becomes
      stronger as the level of complexity of the motor task increases. 

PMID- 25773591
TI  - Impact of anticoagulation on upper-gastrointestinal bleeding in cirrhosis. A
      retrospective multicenter study.
AB  - Recent studies have shown that liver cirrhosis (LC) behaves as an acquired
      hypercoagulable state with increased thrombotic risk. This is why anticoagulation
      therapy (AT) is now frequently used in these patients. Variceal bleeding is a
      severe complication of LC. It is unknown whether AT may impact the outcome of
      bleeding in these patients. Fifty-two patients on AT with upper gastrointestinal
      bleeding (UGIB) were evaluated. Portal vein thrombosis (PVT) and different
      cardiovascular disorders (CVDs) were the indication for AT in 14 and 38 patients,
      respectively. Overall, 104 patients with LC and UGIB not under AT matched for
      severity of LC, age, sex, source of bleeding, and Sequential Organ Failure
      Assessment (SOFA) score served as controls. UGIB was attributed to portal
      hypertension (PH) in 99 (63%) patients and peptic/vascular lesions in 57 (37%).
      Twenty-six (17%) patients experienced 5-day failure; SOFA, source of UGIB, and
      PVT, but not AT, were independent predictors of 5-day failure. In addition,
      independent predictors of 6-week mortality, which was observed in 26 (11%)
      patients, were SOFA, Charlson Comorbidity index, and use of AT for a CVD. There
      were no differences between patients with/without AT in needs for rescue
      therapies, intensive care unit admission, transfusions, and hospital stay.
      CONCLUSIONS: Factors that impact the outcome of UGIB in patients under AT are
      degree of multiorgan failure and comorbidity, but not AT itself.

PMID- 25773592
TI  - Antioxidant activity of high sulfate content derivative of ulvan in
      hyperlipidemic rats.
AB  - High sulfate content derivative of polysaccharide (HU) from Ulva pertusa
      (Chlorophyta) showed strong antioxidant activity in vitro. In the present study,
      in vivo antioxidant activity were tested in liver of hyperlipidemic rats
      including malondialdehyde (MDA), superoxide dismutase (SOD), glutathione
      peroxidase (GSH-Px) and catalase (CAT). The HU groups at the doses of 125 mg/kg
      and 250 mg/kg showed stronger activity on SOD than hyperlipidemimia group
      (P<0.01). The HU groups at the doses of 125 mg/kg and 500 mg/kg could increase
      the activities of GSH-Px obviously (P<0.01) as compared with hyperlipidemic rats.
      It was likely that the sulfate content had significant effect on the antioxidant
      activity in vivo. On the other hand, it may be concluded that, probably due to
      its antioxidant effects, HU is effective in the protection of liver tissue from
      the damage of cholesterol-rich diet rats and that the HU may be of use as an
      antihyperlipidemia agent.

PMID- 25773593
TI  - The group exponential lasso for bi-level variable selection.
AB  - In many applications, covariates possess a grouping structure that can be
      incorporated into the analysis to select important groups as well as important
      members of those groups. One important example arises in genetic association
      studies, where genes may have several variants capable of contributing to
      disease. An ideal penalized regression approach would select variables by
      balancing both the direct evidence of a feature's importance as well as the
      indirect evidence offered by the grouping structure. This work proposes a new
      approach we call the group exponential lasso (GEL) which features a decay
      parameter controlling the degree to which feature selection is coupled together
      within groups. We demonstrate that the GEL has a number of statistical and
      computational advantages over previously proposed group penalties such as the
      group lasso, group bridge, and composite MCP. Finally, we apply these methods to
      the problem of detecting rare variants in a genetic association study. 

PMID- 25773594
TI  - Effect of dipyridamole on myocardial reperfusion injury: A double-blind
      randomized controlled trial in patients undergoing elective coronary artery
      bypass surgery.
AB  - Dipyridamole reduces reperfusion-injury in preclinical trials and may be
      beneficial in patients undergoing coronary angioplasty, but its effect on
      patients undergoing coronary artery bypass grafting (CABG) is unknown. We
      hypothesized that dipyridamole limits myocardial reperfusion-injury in patients
      undergoing CABG. The trial design was a double-blind trial randomizing between
      pretreatment with dipyridamole or placebo. In all, 94 patients undergoing
      elective on-pump CABG were recruited between February 2010 and June 2012. The
      primary endpoint was plasma high-sensitive (hs-) troponin-I at 6, 12, and 24
      hours after reperfusion. Secondary endpoints were the occurrence of bleeding,
      arrhythmias, need for inotropic support, and intensive care unit length of stay.
      Finally, 79 patients (33 dipyridamole) were included in the per-protocol
      analysis. Dipyridamole did not significantly affect postoperative hs-troponin-I
      (change in plasma hs-troponin I -3% [95% confidence interval -23% to 36%]; P >
      0.1). Secondary endpoints did not differ between groups. Dipyridamole prior to
      CABG does not significantly reduce postoperative hs-troponin release. 

PMID- 25773595
TI  - Myristoylome profiling reveals a concerted mechanism of ARF GTPase deacylation by
      the bacterial protease IpaJ.
AB  - N-myristoylation is an essential fatty acid modification that governs the
      localization and activity of cell signaling enzymes, architectural proteins, and
      immune regulatory factors. Despite its importance in health and disease, there
      are currently no methods for reversing protein myristoylation in vivo. Recently,
      the Shigella flexneri protease IpaJ was found to cleave myristoylated glycine of
      eukaryotic proteins, yet the discriminatory mechanisms of substrate selection
      required for targeted demyristoylation have not yet been evaluated. Here, we
      performed global myristoylome profiling of cells treated with IpaJ under distinct
      physiological conditions. The protease is highly promiscuous among diverse N
      myristoylated proteins in vitro but is remarkably specific to Golgi-associated
      ARF/ARL family GTPases during Shigella infection. Reconstitution studies revealed
      a mechanistic framework for substrate discrimination based on IpaJ's function as
      a GTPase "effector" of bacterial origin. We now propose a concerted model for
      IpaJ function that highlights its potential for programmable demyristoylation in
      vivo. 

PMID- 25773596
TI  - Protein polyphosphorylation of lysine residues by inorganic polyphosphate.
AB  - The complexity of higher organisms is not simply a reflection of the number of
      genes. A network of additional regulatory features, including protein post
      translational modifications (PTMs), provides functional complexity otherwise
      inaccessible to a single gene product. Virtually all proteins are targets of
      PTMs. Here we characterize "polyphosphorylation" as the covalent attachment of
      inorganic polyphosphate (polyP) to target proteins. We found that nuclear signal
      recognition 1 (Nsr1) and its interacting partner, topoisomerase 1 (Top1), are
      polyphosphorylated. This modification occurs on lysine (K) residues within a
      conserved N-terminal polyacidic serine (S) and K-rich (PASK) cluster. We show
      that polyphosphorylation negatively regulates Nsr1/Top1 interaction and impairs
      Top1 enzymatic activity. Physiological modulation of cellular levels of polyP
      regulates Top1 activity by modifying its polyphosphorylation status. We propose
      that polyphosphorylation adds an additional layer of regulation to nuclear
      signaling, where many PASK-containing proteins are known to play important roles.

PMID- 25773597
TI  - A diffraction-quality protein crystal processed as an autophagic cargo.
AB  - Crystallization of proteins may occur in the cytosol of a living cell, but how a
      cell responds to intracellular protein crystallization remains unknown. We
      developed a variant of coral fluorescent protein that forms diffraction-quality
      crystals within mammalian cells. This expression system allowed the direct
      determination of its crystal structure at 2.9 A, as well as observation of the
      crystallization process and cellular responses. The micron-sized crystal, which
      emerged rapidly, was a pure assembly of properly folded beta-barrels and was
      recognized as an autophagic cargo that was transferred to lysosomes via a process
      involving p62 and LC3. Several lines of evidence indicated that autophagy was not
      required for crystal nucleation or growth. These findings demonstrate that in
      vivo protein crystals can provide an experimental model to study chemical
      catalysis. This knowledge may be beneficial for structural biology studies on
      normal and disease-related protein aggregation.

PMID- 25773598
TI  - Histone demethylase LSD2 acts as an E3 ubiquitin ligase and inhibits cancer cell
      growth through promoting proteasomal degradation of OGT.
AB  - Histone demethylases play important roles in various biological processes in a
      manner dependent on their demethylase activities. However, little is known about
      their demethylase-independent activities. Here, we report that LSD2, a well-known
      histone H3K4me1/me2 demethylase, possesses an unexpected E3 ubiquitin ligase
      activity. LSD2 directly ubiquitylates and promotes proteasome-dependent
      degradation of O-GlcNAc transferase (OGT), and inhibits A549 lung cancer cell
      growth in a manner dependent on its E3 ligase activity, but not demethylase
      activity. The depletion of LSD2 stabilizes OGT and promotes colony formation of
      293T cells. LSD2 regulates distinct groups of target genes through histone
      demethylase and E3 ligase activities, respectively. Such regulation suggests a
      mechanism through which LSD2 suppresses tumorigenesis by promoting the
      degradation of OGT and other substrates yet to be discovered. Our study reveals
      an antigrowth function of LSD2 dependent on its E3 ligase activity and
      establishes a connection between histone demethylase and ubiquitin-dependent
      pathway. 

PMID- 25773599
TI  - Pausing of RNA polymerase II regulates mammalian developmental potential through
      control of signaling networks.
AB  - The remarkable capacity for pluripotency and self-renewal in embryonic stem cells
      (ESCs) requires a finely tuned transcriptional circuitry wherein the pathways and
      genes that initiate differentiation are suppressed, but poised to respond rapidly
      to developmental signals. To elucidate transcriptional control in mouse ESCs in
      the naive, ground state, we defined the distribution of engaged RNA polymerase II
      (Pol II) at high resolution. We find that promoter-proximal pausing of Pol II is
      most enriched at genes regulating cell cycle and signal transduction and not, as
      expected, at developmental or bivalent genes. Accordingly, ablation of the
      primary pause-inducing factor NELF does not increase expression of lineage
      markers, but instead causes proliferation defects, embryonic lethality, and
      dysregulation of ESC signaling pathways. Indeed, ESCs lacking NELF have
      dramatically attenuated FGF/ERK activity, rendering them resistant to
      differentiation. This work thus uncovers a key role for NELF-mediated pausing in
      establishing the responsiveness of stem cells to developmental cues. 

PMID- 25773601
TI  - Spontaneous repigmentation in an infant with piebaldism.

PMID- 25773600
TI  - Mitochondrial and nuclear accumulation of the transcription factor ATFS-1
      promotes OXPHOS recovery during the UPR(mt).
AB  - Mitochondrial diseases and aging are associated with defects in the oxidative
      phosphorylation machinery (OXPHOS), which are the only complexes composed of
      proteins encoded by separate genomes. To better understand genome coordination
      and OXPHOS recovery during mitochondrial dysfunction, we examined ATFS-1, a
      transcription factor that regulates mitochondria-to-nuclear communication during
      the mitochondrial UPR, via ChIP-sequencing. Surprisingly, in addition to
      regulating mitochondrial chaperone, OXPHOS complex assembly factor, and
      glycolysis genes, ATFS-1 bound directly to OXPHOS gene promoters in both the
      nuclear and mitochondrial genomes. Interestingly, atfs-1 was required to limit
      the accumulation of OXPHOS transcripts during mitochondrial stress, which
      required accumulation of ATFS-1 in the nucleus and mitochondria. Because balanced
      ATFS-1 accumulation promoted OXPHOS complex assembly and function, our data
      suggest that ATFS-1 stimulates respiratory recovery by fine-tuning OXPHOS
      expression to match the capacity of the suboptimal protein-folding environment in
      stressed mitochondria, while simultaneously increasing proteostasis capacity. 

PMID- 25773602
TI  - Protective effect of fucosterol isolated from the edible brown algae, Ecklonia
      stolonifera and Eisenia bicyclis, on tert-butyl hydroperoxide- and tacrine
      induced HepG2 cell injury.
AB  - OBJECTIVES: Fucosterol is the primary sterol found in brown algae. Recently,
      considerable interest has been generated regarding fucosterol due to its
      potential antioxidant, anti-inflammatory and antidiabetic effects. The aim of
      this study was to investigate the protective effects of fucosterol on tert-butyl
      hydroperoxide (t-BHP)- and tacrine-induced oxidative stress in HepG2 cells.
      METHODS: Fucosterol by itself exhibited no cytotoxicity at concentrations below
      100 MUm by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide
      assay. The increased intracellular reactive oxygen species (ROS) and decreased
      glutathione levels observed in t-BHP- and tacrine-treated HepG2 cells were
      ameliorated by fucosterol pretreatment, indicating that the protective effects of
      fucosterol are mediated by the induction of cellular defence mechanisms against
      oxidative stress. Moreover, elevated alanine aminotransferase (ALT) and aspartate
      aminotransferase (AST) levels in tacrine-treated mice were significantly reduced
      after oral administration of fucosterol. KEY FINDINGS: The hepatoprotective
      effects of fucosterol may occur via an increase in the hepatic level of
      glutathione and a decrease in ROS production, thereby preventing hepatic damage
      and the resultant increases in ALT and AST activity. CONCLUSION: These results
      suggest that fucosterol may be an effective hepatoprotective agent that could be
      useful for preventive therapies against oxidative stress-related hepatotoxicity.

PMID- 25773603
TI  - Changing the attitudes of sex studies in science.

PMID- 25773604
TI  - Trends in observation-prone emergency department visits among Michigan children,
      2007-2011.
AB  - OBJECTIVES: To the best of the authors' knowledge, admission of children under
      observation status in community hospitals has not been examined. The hypothesis
      of this study was that there has been an increase in observation charge code use
      over time and variations in the application of observation charge codes across
      hospital types. METHODS: This was a cross-sectional analysis of 5 years (2007
      through 2011) of administrative claims data from Michigan residents enrolled in
      Medicaid, Blue Cross/Blue Shield of Michigan preferred provider organization, and
      Blue Cross Network health maintenance organization compiled into a single data
      set. Emergency department (ED) visits to facilities in Michigan made by children
      (younger than 18 years) were selected. Observation-prone ED visits were
      identified based on the presence of International Classification of Diseases,
      Ninth Revision, Clinical Modification (ICD-9-CM) codes. Counts of observation
      prone ED visits were determined and descriptive statistics were calculated.
      Changes over time in the proportion of visits with observation charge codes by
      hospital type were assessed with chi-square analysis. RESULTS: The observation
      prone ICD-9-CM codes were identified in 881,622 ED visits made by children to 142
      Michigan facilities during the 5-year study period. Overall, the vast majority of
      visits (n = 646,499; 91.0%) with the selected ICD-9-CM codes resulted in
      discharge from the ED without associated observation or inpatient charge codes.
      Among the 64,288 visits that resulted in admission for observation or inpatient
      care, observation charge codes without inpatient charge codes were applied to
      22,933 (35.7%) admissions, observation and inpatient charge codes were applied to
      4,756 (7.4%) admissions, and inpatient charge codes without observation charge
      codes were applied to 36,599 (56.9%) admissions. Hospitals with pediatric ED and
      inpatient services (Type 1 and Type 2 hospitals) had higher proportions of ED
      visits that went on to admission for observation or inpatient care (15.9 and
      10.7%) than hospitals without pediatric ED services (Type 3 and Type 4 hospitals;
      7.2 and 3.7%). The proportion of admissions that had observation charge codes for
      all hospital types increased over time, most prominently among Type 1 and Type 2
      hospitals. CONCLUSIONS: The application of observation charge codes to Michigan
      children with observation-prone conditions has increased over time across all
      hospital types. There is a need to evaluate pediatric observation care in diverse
      settings to compare the effectiveness of different models.

PMID- 25773605
TI  - Pancreatic endotherapy and necrosectomy.
AB  - OPINION STATEMENT: There has been a paradigm shift in the management of
      pancreatic necrosis from open surgical debridement of infected necrosis to
      minimally invasive interventional radiologic, laparoscopic, and endoscopic
      drainage/debridement techniques. A step-up approach from less invasive to the
      more invasive modalities is recommended. An important distinction to make is
      between pseudocysts and walled-off necrosis (WON), as the interventions for each
      are different. Endoscopic or other interventions should be delayed for at least 4
      weeks for collections to encapsulate. Direct endoscopic necrosectomy (DEN) is an
      effective, minimally invasive option. Several variations in the technique,
      including the use of esophageal fully covered self-expanding metal stents (SEMS)
      and lumen-apposing SEMS have recently been described. The incremental
      effectiveness of these stents over conventional techniques needs to be studied.
      Dual-modality drainage with endoscopic transmural stent placement and lavage
      through percutaneous drains is also an effective option with low mortality and
      morbidity. Several minimally invasive surgical options, including video-assisted
      retroperitoneal debridement and sinus tract endoscopy are available and may be
      preferable to open surgical necrosectomy. An algorithmic, multidisciplinary
      management is warranted for successful outcomes. Disconnected pancreatic duct
      syndrome in the setting of necrotizing pancreatitis is challenging; long-term
      endoscopic transmural stent placement and/or distal pancreatectomy are potential
      treatment options.

PMID- 25773606
TI  - Treatment to improve acute kidney injury in cirrhosis.
AB  - OPINION STATEMENT: Acute kidney injury (AKI) is an ominous complication of
      decompensated cirrhosis, which can be fatal if not treated promptly. It is
      important that clinicians recognize that AKI has occurred and institute timely
      treatment. Recent establishment of diagnostic criteria and treatment guidelines
      are most useful, and these will be further refined as treatments are being
      modified to improve patient outcome. To manage such a patient, firstly, the cause
      of the AKI needs to be identified and any precipitating factors corrected.
      Bacterial infections are a common cause of AKI in cirrhosis, and it is
      recommended to offer empirical antibiotics in cases of suspicious bacterial
      infection until all the cultures are negative. Patients should be given albumin
      infusion in doses of 1 g/kg of body weight for at least 2 days. This can improve
      the filling of the central circulation, and also absorb many of the bacterial
      products or inflammatory cytokines that play a role in mediating the renal
      dysfunction. Often, albumin infusion alone may be sufficient to reverse the AKI.
      For patients who have acute or type 1 hepatorenal syndrome (HRS1), which is a
      special form of AKI, pharmacotherapy in the form of vasoconstrictor will be
      needed. The vasoconstrictor can be terlipressin, norepinephrine, or midodrine,
      depending on the local availability of drugs or facilities. Currently,
      approximately 40 % of patients will respond to a combination of vasoconstrictor
      and albumin. All patients with HRS1 should be assessed for liver transplant. If
      accepted for liver transplantation, those patients who do not respond to
      vasocontrictors and albumin need to be started on renal replacement therapy,
      which otherwise has no place in the treatment of HRS1. Once listed, liver
      transplantation should occur promptly, preferable under 2 weeks. Otherwise, the
      chances for renal recovery after liver transplant are significantly reduced,
      necessitating a renal transplant at the future date.

PMID- 25773607
TI  - Efficacy and safety of evolocumab in reducing lipids and cardiovascular events.
AB  - BACKGROUND: Evolocumab, a monoclonal antibody that inhibits proprotein convertase
      subtilisin-kexin type 9 (PCSK9), significantly reduced low-density lipoprotein
      (LDL) cholesterol levels in short-term studies. We conducted two extension
      studies to obtain longer-term data. METHODS: In two open-label, randomized
      trials, we enrolled 4465 patients who had completed 1 of 12 phase 2 or 3 studies
      ("parent trials") of evolocumab. Regardless of study-group assignments in the
      parent trials, eligible patients were randomly assigned in a 2:1 ratio to receive
      either evolocumab (140 mg every 2 weeks or 420 mg monthly) plus standard therapy
      or standard therapy alone. Patients were followed for a median of 11.1 months
      with assessment of lipid levels, safety, and (as a prespecified exploratory
      analysis) adjudicated cardiovascular events including death, myocardial
      infarction, unstable angina, coronary revascularization, stroke, transient
      ischemic attack, and heart failure. Data from the two trials were combined.
      RESULTS: As compared with standard therapy alone, evolocumab reduced the level of
      LDL cholesterol by 61%, from a median of 120 mg per deciliter to 48 mg per
      deciliter (P<0.001). Most adverse events occurred with similar frequency in the
      two groups, although neurocognitive events were reported more frequently in the
      evolocumab group. The risk of adverse events, including neurocognitive events,
      did not vary significantly according to the achieved level of LDL cholesterol.
      The rate of cardiovascular events at 1 year was reduced from 2.18% in the
      standard-therapy group to 0.95% in the evolocumab group (hazard ratio in the
      evolocumab group, 0.47; 95% confidence interval, 0.28 to 0.78; P=0.003).
      CONCLUSIONS: During approximately 1 year of therapy, the use of evolocumab plus
      standard therapy, as compared with standard therapy alone, significantly reduced
      LDL cholesterol levels and reduced the incidence of cardiovascular events in a
      prespecified but exploratory analysis. (Funded by Amgen; OSLER-1 and OSLER-2
      ClinicalTrials.gov numbers, NCT01439880 and NCT01854918.).

PMID- 25773608
TI  - Synchronous intrapulmonary schwannoma and primary lung cancer.

PMID- 25773610
TI  - Cognitive plasticity in older adults: effects of cognitive training and physical
      exercise.
AB  - Cognitive training, physical activity, and exercise have often been reported to
      improve cognitive performance in older adults. This paper reviews some seminal
      and recent studies using these approaches to improve cognition and physical
      functioning in healthy older adults and in patients suffering from non
      neurological chronic medical conditions. Results from cognitive training studies
      suggest that despite performance improvement in trained tasks, transfer effects
      appeared very limited. Surprisingly though, computerized dual-task training has
      been shown to improve balance and postural control in tests of physical
      functioning, suggesting that broad transfer can sometimes be observed. Physical
      exercise intervention studies generally found significant and large improvements
      in physical capacity, in some cognitive domains, and in quality of life. The
      benefits seem to be equivalent between frail and nonfrail participants. Overall,
      results reviewed here support the notion that cognitive plasticity for
      attentional control, as induced by cognitive training or physical activity and
      exercise, is preserved in late adulthood. Moreover, results of studies with
      patients at risk of cognitive decline also suggest that cognitive training and
      exercise interventions are promising nonpharmaceutical tools to help improve
      cognition in older at-risk individuals. 

PMID- 25773611
TI  - Multimodal imaging of temporal processing in typical and atypical language
      development.
AB  - New approaches to understanding language and reading acquisition propose that the
      human brain's ability to synchronize its neural firing rate to syllable-length
      linguistic units may be important to children's ability to acquire human
      language. Yet, little evidence from brain imaging studies has been available to
      support this proposal. Here, we summarize three recent brain imaging (functional
      near-infrared spectroscopy (fNIRS), functional magnetic resonance imaging (fMRI),
      and magnetoencephalography (MEG)) studies from our laboratories with young
      English-speaking children (aged 6-12 years). In the first study (fNIRS), we used
      an auditory beat perception task to show that, in children, the left superior
      temporal gyrus (STG) responds preferentially to rhythmic beats at 1.5 Hz. In the
      second study (fMRI), we found correlations between children's amplitude rise-time
      sensitivity, phonological awareness, and brain activation in the left STG. In the
      third study (MEG), typically developing children outperformed children with
      autism spectrum disorder in extracting words from rhythmically rich foreign
      speech and displayed different brain activation during the learning phase. The
      overall findings suggest that the efficiency with which left temporal regions
      process slow temporal (rhythmic) information may be important for gains in
      language and reading proficiency. These findings carry implications for better
      understanding of the brain's mechanisms that support language and reading
      acquisition during both typical and atypical development. 

PMID- 25773609
TI  - Fertility, pregnancy and childbirth in patients with multiple sclerosis: impact
      of disease-modifying drugs.
AB  - In recent decades, pregnancy-related issues in multiple sclerosis (MS) have
      received growing interest. MS is more frequent in women than in men and typically
      starts during child-bearing age. An increasing number of disease-modifying drugs
      (DMDs) for the treatment of MS are becoming available. Gathering information on
      their influences on pregnancy-related issues is of crucial importance for the
      counselling of MS patients. As for the immunomodulatory drugs (interferons and
      glatiramer acetate), accumulating evidence points to the relative safety of
      pregnancy exposure in terms of maternal and foetal outcomes. In case of higher
      clinical disease activity before pregnancy, these drugs could be continued until
      conception. As for the 'newer' drugs (fingolimod, natalizumab, teriflunomide,
      dimethyl fumarate and alemtuzumab), the information is more limited. Whereas
      fingolimod and teriflunomide are likely associated with an increased risk of
      foetal malformations, the effects of natalizumab, dimethyl fumarate and
      alemtuzumab still need to be ascertained. This article provides a review of the
      available information on the use of DMDs during pregnancy, with a specific focus
      on fertility, foetal development, delivery and breast-feeding. 

PMID- 25773612
TI  - Perspectives on the rhythm-grammar link and its implications for typical and
      atypical language development.
AB  - This paper reviews the mounting evidence for shared cognitive mechanisms and
      neural resources for rhythm and grammar. Evidence for a role of rhythm skills in
      language development and language comprehension is reviewed here in three lines
      of research: (1) behavioral and brain data from adults and children, showing that
      prosody and other aspects of timing of sentences influence online morpho
      syntactic processing; (2) comorbidity of impaired rhythm with grammatical
      deficits in children with language impairment; and (3) our recent work showing a
      strong positive association between rhythm perception skills and expressive
      grammatical skills in young school-age children with typical development. Our
      preliminary follow-up study presented here revealed that musical rhythm
      perception predicted variance in 6-year-old children's production of complex
      syntax, as well as online reorganization of grammatical information
      (transformation); these data provide an additional perspective on the
      hierarchical relations potentially shared by rhythm and grammar. A theoretical
      framework for shared cognitive resources for the role of rhythm in perceiving and
      learning grammatical structure is elaborated on in light of potential
      implications for using rhythm-emphasized musical training to improve language
      skills in children. 

PMID- 25773614
TI  - Short- and long-term rhythmic interventions: perspectives for language
      rehabilitation.
AB  - This paper brings together different perspectives on the investigation and
      understanding of temporal processing and temporal expectations. We aim to bridge
      different temporal deficit hypotheses in dyslexia, dysphasia, or deafness in a
      larger framework, taking into account multiple nested temporal scales. We present
      data testing the hypothesis that temporal attention can be influenced by external
      rhythmic auditory stimulation (i.e., musical rhythm) and benefits subsequent
      language processing, including syntax processing and speech production. We also
      present data testing the hypothesis that phonological awareness can be influenced
      by several months of musical training and, more particularly, rhythmic training,
      which in turn improves reading skills. Together, our data support the hypothesis
      of a causal role of rhythm-based processing for language processing and
      acquisition. These results open new avenues for music-based remediation of
      language and hearing impairment. 

PMID- 25773613
TI  - Neuronal oscillations as a mechanistic substrate of auditory temporal prediction.
AB  - Neuronal oscillations are comprised of rhythmic fluctuations of excitability that
      are synchronized in ensembles of neurons and thus function as temporal filters
      that dynamically organize sensory processing. When perception relies on
      anticipatory mechanisms, ongoing oscillations also provide a neurophysiological
      substrate for temporal prediction. In this article, we review evidence for this
      account with a focus on auditory perception. We argue that such "oscillatory
      temporal predictions" can selectively amplify neuronal sensitivity to inputs that
      occur in a predicted, task-relevant rhythm and optimize temporal selection. We
      elaborate this argument for a prototypic example, speech processing, where
      information is present at multiple time scales, with delta, theta, and low-gamma
      oscillations being specifically and simultaneously engaged, enabling
      multiplexing. We then consider the origin of temporal predictions, specifically
      the idea that the motor system is involved in the generation of such prior
      information. Finally, we place temporal predictions in the general context of
      internal models, discussing how they interact with feature-based or spatial
      predictions. We propose that complementary predictions interact synergistically
      according to a dominance hierarchy, shaping perception in the form of a
      multidimensional filter mechanism. 

PMID- 25773615
TI  - Motor responses to a steady beat.
AB  - It is increasingly well established that music containing an isochronous pulse
      elicits motor responses at the levels of both brain and behavior. Such motor
      responses are often used in pedagogical and clinical practice to induce movement,
      particularly where motor functions are impaired. However, the complex nature of
      such apparently universal human responses has, arguably, not received adequate
      research attention to date. In particular, it should be noted that many adults,
      including those with disabilities, find it somewhat difficult to synchronize
      their movements with a beat with perfect accuracy; indeed, perfecting the skill
      of being musically "in time" can take years of training during childhood. Further
      research is needed on the nature of both the specificity and range of motor
      responses that can arise from the perception of a steady auditory pulse, with
      different populations, musical stimuli, conditions, and required levels of
      accuracy in order to better understand and capture the potential value of the
      musical beat as a pedagogical and therapeutic tool. 

PMID- 25773616
TI  - Rhythm and interpersonal synchrony in early social development.
AB  - Adults who engage in synchronous movement to music later report liking each other
      better, remembering more about each other, trusting each other more, and are more
      likely to cooperate with each other compared to adults who engage in asynchronous
      movements. Although poor motor coordination limits infants' ability to entrain to
      a musical beat, they perceive metrical structure in auditory rhythm patterns,
      their movements are affected by the tempo of music they hear, and if they are
      bounced by an adult to a rhythm pattern, the manner of this bouncing can affect
      their auditory interpretation of the meter of that pattern. In this paper, we
      review studies showing that by 14 months of age, infants who are bounced in
      synchrony with an adult subsequently show more altruistic behavior toward that
      adult in the form of handing back objects "accidentally" dropped by the adult
      compared to infants who are bounced asynchronously with the adult. Furthermore,
      increased helpfulness is directed at the synchronized bounce partner, but not at
      a neutral stranger. Interestingly, however, helpfulness does generalize to a
      "friend" of the synchronized bounce partner. In sum, synchronous movement between
      infants and adults has a powerful effect on infants' expression of directed
      prosocial behavior. 

PMID- 25773617
TI  - Familiarity with music increases walking speed in rhythmic auditory cuing.
AB  - Rhythmic auditory stimulation (RAS) is a gait rehabilitation method in which
      patients synchronize footsteps to a metronome or musical beats. Although RAS with
      music can ameliorate gait abnormalities, outcomes vary, possibly because music
      properties, such as groove or familiarity, differ across interventions. To
      optimize future interventions, we assessed how initially familiar and unfamiliar
      low-groove and high-groove music affected synchronization accuracy and gait in
      healthy individuals. We also experimentally increased music familiarity using
      repeated exposure to initially unfamiliar songs. Overall, familiar music elicited
      faster stride velocity and less variable strides, as well as better
      synchronization performance (matching of step tempo to beat tempo). High-groove
      music, as reported previously, led to faster stride velocity than low-groove
      music. We propose two mechanisms for familiarity's effects. First, familiarity
      with the beat structure reduces cognitive demands of synchronizing, leading to
      better synchronization performance and faster, less variable gait. Second,
      familiarity might have elicited faster gait by increasing enjoyment of the music,
      as enjoyment was higher after repeated exposure to initially low-enjoyment songs.
      Future studies are necessary to dissociate the contribution of these mechanisms
      to the observed RAS effects of familiar music on gait. 

PMID- 25773618
TI  - Can rhythmic auditory cuing remediate language-related deficits in Parkinson's
      disease?
AB  - Neurodegenerative changes of the basal ganglia in idiopathic Parkinson's disease
      (IPD) lead to motor deficits as well as general cognitive decline. Given these
      impairments, the question arises as to whether motor and nonmotor deficits can be
      ameliorated similarly. We reason that a domain-general sensorimotor circuit
      involved in temporal processing may support the remediation of such deficits.
      Following findings that auditory cuing benefits gait kinematics, we explored
      whether reported language-processing deficits in IPD can also be remediated via
      auditory cuing. During continuous EEG measurement, an individual diagnosed with
      IPD heard two types of temporally predictable but metrically different auditory
      beat-based cues: a march, which metrically aligned with the speech accent
      structure, a waltz that did not metrically align, or no cue before listening to
      naturally spoken sentences that were either grammatically well formed or were
      semantically or syntactically incorrect. Results confirmed that only the cuing
      with a march led to improved computation of syntactic and semantic information.
      We infer that a marching rhythm may lead to a stronger engagement of the
      cerebello-thalamo-cortical circuit that compensates dysfunctional striato
      cortical timing. Reinforcing temporal realignment, in turn, may lead to the
      timely processing of linguistic information embedded in the temporally variable
      speech signal. 

PMID- 25773619
TI  - Moving with music for stroke rehabilitation: a sonification feasibility study.
AB  - Gross-motor impairments are common after stroke, but efficacious and motivating
      therapies for these impairments are scarce. We present a novel musical
      sonification therapy especially designed to retrain gross-motor functions. Four
      stroke patients were included in a clinical pre-post feasibility study and were
      trained with our sonification training. Patients' upper-extremity functions and
      their psychological states were assessed before and after training. The four
      patients were subdivided into two groups, with both groups receiving 9 days of
      musical sonification therapy (music group, MG) or a sham sonification training
      (control group, CG). The only difference between these training protocols was
      that, in the CG, no sound was played back. During the training the patients
      initially explored the acoustic effects of their arm movements, and at the end of
      the training the patients played simple melodies by moving their arms. The two
      patients in the MG improved in nearly all motor function tests after the
      training. They also reported in the stroke impact scale, which assesses well
      being, memory, thinking, and social participation, to be less impaired by the
      stroke. The two patients in the CG did benefit less from the movement training.
      Taken together, musical sonification may be a promising therapy for impairments
      after stroke. 

PMID- 25773620
TI  - Effects of musically cued gait training in Parkinson's disease: beyond a motor
      benefit.
AB  - Auditory stimulation via rhythmic cues can be used successfully in the
      rehabilitation of motor function in patients with motor disorders. A prototypical
      example is provided by dysfunctional gait in patients with idiopathic Parkinson's
      disease (PD). Coupling steps to external rhythmic cues (the beat of music or the
      sounds of a metronome) leads to long-term motor improvements, such as increased
      walking speed and greater stride length. These effects are likely to be
      underpinned by compensatory brain mechanisms involving cerebellar-thalamocortical
      networks. Because these areas are also involved in perceptual and motor timing,
      parallel improvement in timing tasks is expected in PD beyond purely motor
      benefits. In keeping with this idea, we report here recent behavioral data
      showing beneficial effects of musically cued gait training (MCGT) on gait
      performance (i.e., increased stride length and speed), perceptual timing (e.g.,
      discriminating stimulus durations), and sensorimotor timing abilities (i.e., in
      paced tapping tasks) in PD patients. Particular attention is paid to individual
      differences in timing abilities in PD, thus paving the ground for an
      individualized MCGT-based therapy. 

PMID- 25773621
TI  - Alignment strategies for the entrainment of music and movement rhythms.
AB  - Theories of entrainment assume that spontaneous entrainment emerges from dynamic
      laws that operate via mediators on interactions, whereby entrainment is
      facilitated if certain conditions are fulfilled. In this study, we show that
      mediators can be built that affect the entrainment of human locomotion to music.
      More specifically, we built D-Jogger, a music player that functions as a mediator
      between music and locomotion rhythms. The D-Jogger makes it possible to
      manipulate the timing differences between salient moments of the rhythms (beats
      and footfalls) through the manipulation of the musical period and phase, which
      affect the condition in which entrainment functions. We conducted several
      experiments to explore different strategies for manipulating the entrainment of
      locomotion and music. The results of these experiments showed that spontaneous
      entrainment can be manipulated, thereby suggesting different strategies on how to
      embark. The findings furthermore suggest a distinction among different modalities
      of entrainment: finding the beat (the most difficult part of entrainment),
      keeping the beat (easier, as a temporal scheme has been established), and being
      in phase (no entrainment is needed because the music is always adapted to the
      human rhythm). This study points to a new avenue of research on entrainment and
      opens new perspectives for the neuroscience of music. 

PMID- 25773622
TI  - Sound-induced stabilization of breathing and moving.
AB  - In humans and other animals, the locomotor and respiratory systems are coupled
      together through mechanical, neurophysiological, and informational interactions.
      At a macroscopic observer-environment level, these three types of interactions
      produce locomotor-respiratory coupling (LRC), whose dynamics are evaluated in
      this paper. A formal analysis of LRC is presented, exploiting tools from
      synchronization theories and nonlinear dynamics. The results of two recent
      studies, in which participants were instructed to cycle or exhale at a natural
      frequency or in synchrony with an external rhythmic sound, are discussed. The
      metronome was either absent or present (study 1) and close to or far from the
      natural frequency of the cycling and breathing systems (study 2). The results
      evidenced a stabilization of cycling, breathing, and LRC when sound was present
      compared to when it was absent. A decrease in oxygen consumption was also
      observed, accompanying the increase in sound-induced LRC stabilization. These
      results obtained with a simple rhythmic metronome beat have consequences for
      exercising while listening to music; the consequences are further explored here. 

PMID- 25773623
TI  - Modeling effects of cerebellar and basal ganglia lesions on adaptation and
      anticipation during sensorimotor synchronization.
AB  - This study addressed the role of subcortical brain structures in temporal
      adaptation and anticipation during sensorimotor synchronization. The performance
      of patients with cerebellar or basal ganglia lesions was compared with that of
      healthy control participants on tasks requiring the synchronization of drum
      strokes with adaptive and tempo-changing auditory pacing sequences. The precision
      of sensorimotor synchronization was generally lower in patients relative to
      controls (i.e., variability of asynchronies was higher in patients), although
      synchronization accuracy (mean asynchrony) was commensurate. A computational
      model of adaptation and anticipation (ADAM) was used to examine potential sources
      of individual differences in precision by estimating participants' use of error
      correction, temporal prediction, and the amount of variability associated with
      central timekeeping and peripheral motor processes. Parameter estimates based on
      ADAM indicate that impaired precision was attributable to increased variability
      of timekeeper and motor processes as well as to reduced temporal prediction in
      both patient groups. Adaptive processes related to continuously applied error
      correction were, by contrast, intact in patients. These findings highlight the
      importance of investigating how subcortical structures, including the cerebellum
      and basal ganglia, interact with a broader network of cortical regions to support
      temporal adaptation and anticipation during sensorimotor synchronization. 

PMID- 25773625
TI  - Acquisition and reacquisition of motor coordination in musicians.
AB  - Precise control of movement timing plays a key role in musical performance. This
      motor skill requires coordination across multiple joints and muscles, which is
      acquired through extensive musical training from childhood. However, extensive
      training has a potential risk of causing neurological disorders that impair fine
      motor control, such as task-specific tremor and focal dystonia. Recent
      technological advances in measurement and analysis of biological data, as well as
      noninvasive manipulation of neuronal activities, have promoted the understanding
      of computational and neurophysiological mechanisms underlying acquisition, loss,
      and reacquisition of dexterous movements through musical practice and
      rehabilitation. This paper aims to provide an overview of the behavioral and
      neurophysiological basis of motor virtuosity and disorder in musicians,
      representative extremes of human motor skill. We also report novel evidence of
      effects of noninvasive neurorehabilitation that combined transcranial direct
      current stimulation and motor rehabilitation over multiple days on musician's
      dystonia, which offers a promising therapeutic means. 

PMID- 25773624
TI  - Impaired movement timing in neurological disorders: rehabilitation and treatment
      strategies.
AB  - Timing abnormalities have been reported in many neurological disorders, including
      Parkinson's disease (PD). In PD, motor-timing impairments are especially
      debilitating in gait. Despite impaired audiomotor synchronization, PD patients'
      gait improves when they walk with an auditory metronome or with music. Building
      on that research, we make recommendations for optimizing sensory cues to improve
      the efficacy of rhythmic cuing in gait rehabilitation. Adaptive rhythmic
      metronomes (that synchronize with the patient's walking) might be especially
      effective. In a recent study we showed that adaptive metronomes synchronized
      consistently with PD patients' footsteps without requiring attention; this
      improved stability and reinstated healthy gait dynamics. Other strategies could
      help optimize sensory cues for gait rehabilitation. Groove music strongly engages
      the motor system and induces movement; bass-frequency tones are associated with
      movement and provide strong timing cues. Thus, groove and bass-frequency pulses
      could deliver potent rhythmic cues. These strategies capitalize on the close
      neural connections between auditory and motor networks; and auditory cues are
      typically preferred. However, moving visual cues greatly improve visuomotor
      synchronization and could warrant examination in gait rehabilitation. Together, a
      treatment approach that employs groove, auditory, bass-frequency, and adaptive
      (GABA) cues could help optimize rhythmic sensory cues for treating motor and
      timing deficits. 

PMID- 25773626
TI  - Associations between motor timing, music practice, and intelligence studied in a
      large sample of twins.
AB  - Music performance depends critically on precise processing of time. A common
      model behavior in studies of motor timing is isochronous serial interval
      production (ISIP), that is, hand/finger movements with a regular beat. ISIP
      accuracy is related to both music practice and intelligence. Here we present a
      study of these associations in a large twin cohort, demonstrating that the
      effects of music practice and intelligence on motor timing are additive, with no
      significant multiplicative (interaction) effect. Furthermore, the association
      between music practice and motor timing was analyzed with the use of a co-twin
      control design using intrapair differences. These analyses revealed that the
      phenotypic association disappeared when all genetic and common environmental
      factors were controlled. This suggests that the observed association may not
      reflect a causal effect of music practice on ISIP performance but rather reflect
      common influences (e.g., genetic effects) on both outcomes. The relevance of
      these findings for models of practice and expert performance is discussed. 

PMID- 25773628
TI  - Dance and the brain: a review.
AB  - Dance is a universal form of human expression that offers a rich source for
      scientific study. Dance provides a unique opportunity to investigate brain
      plasticity and its interaction with behavior. Several studies have investigated
      the behavioral correlates of dance, but less is known about the brain basis of
      dance. Studies on dance observation suggest that long- and short-term dance
      training affect brain activity in the action observation and simulation networks.
      Despite methodological challenges, the feasibility of conducting neuroimaging
      while dancing has been demonstrated, and several brain regions have been
      implicated in dance execution. Preliminary work from our laboratory suggests that
      long-term dance training changes both gray and white matter structure. This
      article provides a critical summary of work investigating the neural correlates
      of dance. It covers functional neuroimaging studies of dance observation and
      performance as well as structural neuroimaging studies of expert dancers. To
      stimulate ongoing dialogue between dance and science, future directions in dance
      and brain research as well as implications are discussed. Research on the
      neuroscience of dance will lead to a better understanding of brain-behavior
      relationships and brain plasticity in experts and nonexperts and can be applied
      to the development of dance-based therapy programs. 

PMID- 25773627
TI  - Dance experience sculpts aesthetic perception and related brain circuits.
AB  - Previous research on aesthetic preferences demonstrates that people are more
      likely to judge a stimulus as pleasing if it is familiar. Although general
      familiarity and liking are related, it is less clear how motor familiarity, or
      embodiment, relates to a viewer's aesthetic appraisal. This study directly
      compared how learning to embody an action impacts the neural response when
      watching and aesthetically evaluating the same action. Twenty-two participants
      trained for 4 days on dance sequences. Each day they physically rehearsed one set
      of sequences, passively watched a second set, listened to the music of a third
      set, and a fourth set remained untrained. Functional MRI was obtained prior to
      and immediately following the training period, as were affective and physical
      ability ratings for each dance sequence. This approach enabled precise comparison
      of self-report methods of embodiment with nonbiased, empirical measures of action
      performance. Results suggest that after experience, participants most enjoy
      watching those dance sequences they danced or observed. Moreover, brain regions
      involved in mediating the aesthetic response shift from subcortical regions
      associated with dopaminergic reward processing to posterior temporal regions
      involved in processing multisensory integration, emotion, and biological motion. 

PMID- 25773629
TI  - Music training and inhibitory control: a multidimensional model.
AB  - Training programs aimed to improve cognitive skills have either yielded mixed
      results or remain to be validated. The limited benefits of such regimens are
      largely attributable to weak understanding of (1) how (and which) interventions
      provide the most cognitive improvements; and (2) how brain networks and neural
      mechanisms that underlie specific cognitive abilities can be modified
      selectively. Studies indicate that music training leads to robust and long
      lasting benefits to behavior. Importantly, behavioral advantages conferred by
      music extend beyond perceptual abilities to even nonauditory functions, such as
      inhibitory control (IC) and its neural correlates. Alternative forms of arts
      engagement or brain training do not appear to yield such enhancements, which
      suggests that music uniquely taps into brain networks subserving a variety of
      auditory as well as domain-general mechanisms such as IC. To account for such
      widespread benefits of music training, we propose a framework of transfer effects
      characterized by three dimensions: level of processing, nature of the transfer,
      and involvement of executive functions. We suggest that transfer of skills is
      mediated through modulation of general cognitive processes, in particular IC. We
      believe that this model offers a viable framework to test the extent and
      limitations of music-related changes. 

PMID- 25773630
TI  - Promises of formal and informal musical activities in advancing neurocognitive
      development throughout childhood.
AB  - Adult musicians show superior neural sound discrimination when compared to
      nonmusicians. However, it is unclear whether these group differences reflect the
      effects of experience or preexisting neural enhancement in individuals who seek
      out musical training. Tracking how brain function matures over time in musically
      trained and nontrained children can shed light on this issue. Here, we review our
      recent longitudinal event-related potential (ERP) studies that examine how formal
      musical training and less formal musical activities influence the maturation of
      brain responses related to sound discrimination and auditory attention. These
      studies found that musically trained school-aged children and preschool-aged
      children attending a musical playschool show more rapid maturation of neural
      sound discrimination than their control peers. Importantly, we found no evidence
      for pretraining group differences. In a related cross-sectional study, we found
      ERP and behavioral evidence for improved executive functions and control over
      auditory novelty processing in musically trained school-aged children and
      adolescents. Taken together, these studies provide evidence for the causal role
      of formal musical training and less formal musical activities in shaping the
      development of important neural auditory skills and suggest transfer effects with
      domain-general implications. 

PMID- 25773631
TI  - Emergence of biological markers of musicianship with school-based music
      instruction.
AB  - Musician children and adults demonstrate biological distinctions in auditory
      processing relative to nonmusicians. For example, musician children and adults
      have more robust neural encoding of speech harmonics, more adaptive sound
      processing, and more precise neural encoding of acoustically similar sounds;
      these enhancements may contribute to musicians' linguistic advantages, such as
      for hearing speech in noise and reading. Such findings have inspired proposals
      that the auditory and cognitive stimulation induced by musical practice renders
      musicians enhanced according to biological metrics germane to communication.
      Cross-sectional methodologies comparing musicians with nonmusicians, however, are
      limited by the inability to disentangle training-related effects from demographic
      and innate qualities that may predistinguish musicians. Over the past several
      years, our laboratory has addressed this problem by examining the emergence of
      neural markers of musicianship in children and adolescents using longitudinal
      approaches to track the development of biological indices of speech processing.
      This work was conducted in partnership with successful community-based music
      programs, thus avoiding reliance on a synthetic program for the purposes of
      laboratory study. Outcomes indicate that many of musicians' auditory-related
      biological enhancements emerge with training and may promote the acquisition of
      language skills, including in at-risk populations. 

PMID- 25773632
TI  - Music training and speech perception: a gene-environment interaction.
AB  - Claims of beneficial side effects of music training are made for many different
      abilities, including verbal and visuospatial abilities, executive functions,
      working memory, IQ, and speech perception in particular. Such claims assume that
      music training causes the associations even though children who take music
      lessons are likely to differ from other children in music aptitude, which is
      associated with many aspects of speech perception. Music training in childhood is
      also associated with cognitive, personality, and demographic variables, and it is
      well established that IQ and personality are determined largely by genetics.
      Recent evidence also indicates that the role of genetics in music aptitude and
      music achievement is much larger than previously thought. In short, music
      training is an ideal model for the study of gene-environment interactions but far
      less appropriate as a model for the study of plasticity. Children seek out
      environments, including those with music lessons, that are consistent with their
      predispositions; such environments exaggerate preexisting individual differences.

PMID- 25773633
TI  - NICU music therapy: song of kin as critical lullaby in research and practice.
AB  - Music therapy can improve neonatal function and reduce anxiety in parents during
      neonatal intensive care unit (NICU) stays. Live music entrained to an infant's
      observed vital signs, provided by a certified music therapist with First Sounds
      RBL (rhythm, breath, and lullaby) training, enhanced bonding for infant-parent
      dyads and triads. The author's song of kin intervention, which employs parent
      selected songs, is compared to the presentation of a well-known folk theme
      ("Twinkle") in 272 neonates. Culturally based, parent-selected, personalized
      musical tunes provided in song, as a noninvasive intervention, foster optimal,
      continuous quality of care. Music psychotherapy sessions for parents before
      working with their infants can instill a potent means of nonconfrontational
      support, allowing for expression of fear or anxiety related to the premature
      birth. Although most attention is typically directed to their infant, using music
      can support the parents' grief and assist in the expression of hope that can
      instill a sense of security and containment. From the NICU to home, a familiar
      thread-line theme can be resourced directly from the family and/or parent and
      applied effortlessly throughout the growing baby's transitional moments. 

PMID- 25773634
TI  - Musical affect regulation in infancy.
AB  - Adolescents and adults commonly use music for various forms of affect regulation,
      including relaxation, revitalization, distraction, and elicitation of pleasant
      memories. Mothers throughout the world also sing to their infants, with affect
      regulation as the principal goal. To date, the study of maternal singing has
      focused largely on its acoustic features and its consequences for infant
      attention. We describe recent laboratory research that explores the consequences
      of singing for infant affect regulation. Such work reveals that listening to
      recordings of play songs can maintain 6- to 9-month-old infants in a relatively
      contented or neutral state considerably longer than recordings of infant-directed
      or adult-directed speech. When 10-month-old infants fuss or cry and are highly
      aroused, mothers' multimodal singing is more effective than maternal speech at
      inducing recovery from such distress. Moreover, play songs are more effective
      than lullabies at reducing arousal in Western infants. We explore the
      implications of these findings along with possible practical applications. 

PMID- 25773635
TI  - Music-evoked emotions: principles, brain correlates, and implications for
      therapy.
AB  - This paper describes principles underlying the evocation of emotion with music:
      evaluation, resonance, memory, expectancy/tension, imagination, understanding,
      and social functions. Each of these principles includes several subprinciples,
      and the framework on music-evoked emotions emerging from these principles and
      subprinciples is supposed to provide a starting point for a systematic, coherent,
      and comprehensive theory on music-evoked emotions that considers both reception
      and production of music, as well as the relevance of emotion-evoking principles
      for music therapy. 

PMID- 25773636
TI  - Musical pleasure and reward: mechanisms and dysfunction.
AB  - Most people derive pleasure from music. Neuroimaging studies show that the reward
      system of the human brain is central to this experience. Specifically, the dorsal
      and ventral striatum release dopamine when listening to pleasurable music, and
      activity in these structures also codes the reward value of musical excerpts.
      Moreover, the striatum interacts with cortical mechanisms involved in perception
      and valuation of musical stimuli. Recent studies have begun to explore individual
      differences in the way that this complex system functions. Development of a
      questionnaire for music reward experiences has allowed the identification of
      separable factors associated with musical pleasure, described as music-seeking,
      emotion-evocation, mood regulation, sensorimotor, and social factors. Applying
      this questionnaire to a large sample uncovered approximately 5% of the population
      with low sensitivity to musical reward in the absence of generalized anhedonia or
      depression. Further study of this group revealed that there are individuals who
      respond normally both behaviorally and psychophysiologically to rewards other
      than music (e.g., monetary value) but do not experience pleasure from music
      despite normal music perception ability and preserved ability to identify
      intended emotions in musical passages. This specific music anhedonia bears
      further study, as it may shed light on the function and dysfunction of the reward
      system. 

PMID- 25773637
TI  - Music and emotions: from enchantment to entrainment.
AB  - Producing and perceiving music engage a wide range of sensorimotor, cognitive,
      and emotional processes. Emotions are a central feature of the enjoyment of
      music, with a large variety of affective states consistently reported by people
      while listening to music. However, besides joy or sadness, music often elicits
      feelings of wonder, nostalgia, or tenderness, which do not correspond to emotion
      categories typically studied in neuroscience and whose neural substrates remain
      largely unknown. Here we review the similarities and differences in the neural
      substrates underlying these "complex" music-evoked emotions relative to other
      more "basic" emotional experiences. We suggest that these emotions emerge through
      a combination of activation in emotional and motivational brain systems (e.g.,
      including reward pathways) that confer its valence to music, with activation in
      several other areas outside emotional systems, including motor, attention, or
      memory-related regions. We then discuss the neural substrates underlying the
      entrainment of cognitive and motor processes by music and their relation to
      affective experience. These effects have important implications for the potential
      therapeutic use of music in neurological or psychiatric diseases, particularly
      those associated with motor, attention, or affective disturbances. 

PMID- 25773638
TI  - Preservation of musical memory and engagement in healthy aging and Alzheimer's
      disease.
AB  - In striking contrast to the difficulties with new learning and episodic memories
      in aging and especially in Alzheimer's disease (AD), musical long-term memories
      appear to be largely preserved. Evidence for spared musical memories in aging and
      AD is reviewed here. New data involve the development of a Musical Engagement
      Questionnaire especially designed for use with AD patients. The questionnaire
      assesses behavioral responses to music and is answered by the care partner.
      Current results show that, despite cognitive loss, persons with mild to moderate
      AD preserve musical engagement and music seeking. Familiar music evokes personal
      autobiographical memories for healthy younger and older adults as well and for
      those with mild to moderate AD. It is argued that music is a prime candidate for
      being a stimulus for cognitive stimulation because musical memories and
      associated emotions may be readily evoked; that is, they are strong and do not
      need to be repaired. Working with and through music as a resource may enhance
      social and communication functions. 

PMID- 25773639
TI  - Functional MRI of music emotion processing in frontotemporal dementia.
AB  - Frontotemporal dementia is an important neurodegenerative disorder of younger
      life led by profound emotional and social dysfunction. Here we used fMRI to
      assess brain mechanisms of music emotion processing in a cohort of patients with
      frontotemporal dementia (n = 15) in relation to healthy age-matched individuals
      (n = 11). In a passive-listening paradigm, we manipulated levels of emotion
      processing in simple arpeggio chords (mode versus dissonance) and emotion
      modality (music versus human emotional vocalizations). A complex profile of
      disease-associated functional alterations was identified with separable
      signatures of musical mode, emotion level, and emotion modality within a common,
      distributed brain network, including posterior and anterior superior temporal and
      inferior frontal cortices and dorsal brainstem effector nuclei. Separable
      functional signatures were identified post-hoc in patients with and without
      abnormal craving for music (musicophilia): a model for specific abnormal
      emotional behaviors in frontotemporal dementia. Our findings indicate the
      potential of music to delineate neural mechanisms of altered emotion processing
      in dementias, with implications for future disease tracking and therapeutic
      strategies. 

PMID- 25773640
TI  - Musical tasks targeting preserved and impaired functions in two dementias.
AB  - Studies of musical abilities in dementia have for the most part been rather
      general assessments of abilities, for instance, assessing retention of music
      learned premorbidly. Here, we studied patients with dementias with contrasting
      cognitive profiles to explore specific aspects of music cognition under
      challenge. Patients suffered from Alzheimer's disease (AD), in which a primary
      impairment is in forming new declarative memories, or Lewy body disease (PD/LBD),
      a type of parkinsonism in which executive impairments are prominent. In the AD
      patients, we examined musical imagery. Behavioral and neural evidence confirms
      involvement of perceptual networks in imagery, and these are relatively spared in
      early stages of the illness. Thus, we expected patients to have relatively intact
      imagery in a mental pitch comparison task. For the LBD patients, we tested
      whether executive dysfunction would extend to music. We probed inhibitory skills
      by asking for a speeded pitch or timbre judgment when the irrelevant dimension
      was held constant or also changed. Preliminary results show that AD patients
      score similarly to controls in the imagery tasks, but PD/LBD patients are
      impaired relative to controls in suppressing some irrelevant musical dimensions,
      particularly when the required judgment varies from trial to trial. 

PMID- 25773641
TI  - Efficacy of musical interventions in dementia: methodological requirements of
      nonpharmacological trials.
AB  - The management of patients with Alzheimer's disease is a significant public
      health problem given the limited effectiveness of pharmacological therapies
      combined with iatrogenic effects of drug treatments in dementia. Consequently,
      the development of nondrug care, such as musical interventions, has become a
      necessity. The experimental rigor of studies in this area, however, is often
      lacking. It is therefore difficult to determine the impact of musical
      interventions on patients with dementia. As part of a series of studies, we
      carried out randomized controlled trials to compare the effectiveness of musical
      activities to other pleasant activities on various functions in patients with
      severe Alzheimer's disease. The data obtained in these trials are discussed in
      light of the methodological constraints and requirements specific to these
      clinical studies. Although the results demonstrate the power of music on the
      emotional and behavioral status of patients, they also suggest that other
      pleasant activities (e.g., cooking) are also effective, leaving open the question
      about the specific benefits of music in patients with dementia. All these
      findings highlight the promising potential for nonpharmacological treatments to
      improve the well-being of patients living in residential care and to reduce
      caregiver burden. 

PMID- 25773642
TI  - Music therapy with disorders of consciousness: current evidence and emergent
      evidence-based practice.
AB  - Patients with prolonged disorders of consciousness (PDOC) stemming from acquired
      brain injury present one of the most challenging clinical populations in
      neurological rehabilitation. Because of the complex clinical presentation of PDOC
      patients, treatment teams are confronted with many medicolegal, ethical,
      philosophical, moral, and religious issues in day-to-day care. Accurate diagnosis
      is of central concern, relying on creative approaches from skilled clinical
      professionals using combined behavioral and neurophysiological measures. This
      paper presents the latest evidence for using music as a diagnostic tool with
      PDOC, including recent developments in music therapy interventions and
      measurement. We outline standardized clinical protocols and behavioral measures
      to produce diagnostic outcomes and examine recent research illustrating a range
      of benefits of music-based methods at behavioral, cardiorespiratory, and cortical
      levels using video, electrocardiography, and electroencephalography methods.
      These latest developments are discussed in the context of evidence-based practice
      in rehabilitation with clinical populations. 

PMID- 25773644
TI  - Introduction to the Neurosciences and Music V: cognitive stimulation and
      rehabilitation.

PMID- 25773643
TI  - Neurological and developmental approaches to poor pitch perception and
      production.
AB  - Whereas much of research in music and neuroscience is aimed at understanding the
      mechanisms by which the human brain facilitates music, emerging interest in the
      neuromusic community aims to translate basic music research into clinical and
      educational applications. In the present paper, we explore the problems of poor
      pitch perception and production from both neurological and
      developmental/educational perspectives. We begin by reviewing previous and novel
      findings on the neural regulation of pitch perception and production. We then
      discuss issues in measuring singing accuracy consistently between the laboratory
      and educational settings. We review the Seattle Singing Accuracy Protocol--a new
      assessment tool that we hope can be adopted by cognitive psychologists as well as
      music educators-and we conclude with some suggestions that the present
      interdisciplinary approach might offer for future research.

PMID- 25773645
TI  - Mechanisms of cholesterol and saturated fatty acid lowering by Quillaja saponaria
      extract, studied by in vitro digestion model.
AB  - Quillaja saponin extracts are known to reduce plasma cholesterol levels in
      humans. Here we study the mechanism of this effect with Quillaja Dry saponin
      extract (QD). In vitro model of triglyceride lipolysis is used to quantify the
      effect of QD on the solubilization of cholesterol and of the lipolysis products
      (fatty acids and monoglycerides) in the dietary mixed micelles (DMM). We found
      that QD extract decreases significantly both the cholesterol (from 80% to 20%)
      and saturated fatty acids (SFA, from 70% to 10%) solubilised in DMM. Series of
      dedicated experiments prove that QD may act by two mechanisms: (1) direct
      precipitation of cholesterol and (2) displacement of cholesterol from the DMM.
      Both mechanisms lead to increased cholesterol precipitation and, thus, render
      cholesterol bio-inaccessible. We prove also that the saponin molecules are not
      the active component of QD, because highly purified Quillaja extract with very
      similar saponin composition does not exhibit cholesterol-lowering or SFA-lowering
      effect. The effect of QD extract on cholesterol solubilisation is most probably
      caused by the high-molecular weight polyphenol molecules, present in this
      extract. The reduced SFA solubilisation is caused by Ca(2+) ions of relatively
      high concentration (1.25 wt%), also present in QD extract, which precipitate the
      fatty acids into calcium soaps. 

PMID- 25773647
TI  - Erratum: correction to: the pharmacotherapy of male hypogonadism besides
      androgens.

PMID- 25773648
TI  - Many-body effects in nanocrystal superlattices: departure from sphere packing
      explains stability of binary phases.
AB  - This work analyzes the role of hydrocarbon ligands in the self-assembly of
      nanocrystal (NC) superlattices. Typical NCs, composed of an inorganic core of
      radius R and a layer of capping ligands with length L, can be described as soft
      spheres with softness parameter L/R. Using particle tracking measurements of
      transmission electron microscopy images, we find that close-packed NCs, like
      their hard-sphere counterparts, fill space at approximately 74% density
      independent of softness. We uncover deformability of the ligand capping layer
      that leads to variable effective NC size in response to the coordination
      environment. This effect plays an important role in the packing of particles in
      binary nanocrystal superlattices (BNSLs). Measurements on BNSLs composed of NCs
      of varying softness in several coordination geometries indicate that NCs deform
      to produce dense BNSLs that would otherwise be low-density arrangements if the
      particles remained spherical. Consequently, rationalizing the mixing of two NC
      species during BNSL self-assembly need not employ complex energetic interactions.
      We summarize our analysis in a set of packing rules. These findings contribute to
      a general understanding of entropic effects during crystallization of deformable
      objects (e.g., nanoparticles, micelles, globular proteins) that can adapt their
      shape to the local coordination environment. 

PMID- 25773646
TI  - Immediate memory for "when, where and what": Short-delay retrieval using dynamic
      naturalistic material.
AB  - We investigated the neural correlates supporting three kinds of memory judgments
      after very short delays using naturalistic material. In two functional magnetic
      resonance imaging (fMRI) experiments, subjects watched short movie clips, and
      after a short retention (1.5-2.5 s), made mnemonic judgments about specific
      aspects of the clips. In Experiment 1, subjects were presented with two scenes
      and required to either choose the scene that happened earlier in the clip ("scene
      chronology"), or with a correct spatial arrangement ("scene-layout"), or that had
      been shown ("scene-recognition"). To segregate activity specific to seen versus
      unseen stimuli, in Experiment 2 only one probe image was presented (either target
      or foil). Across the two experiments, we replicated three patterns underlying the
      three specific forms of memory judgment. The precuneus was activated during
      temporal-order retrieval, the superior parietal cortex was activated bilaterally
      for spatial-related configuration judgments, whereas the medial frontal cortex
      during scene recognition. Conjunction analyses with a previous study that used
      analogous retrieval tasks, but a much longer delay (>1 day), demonstrated that
      this dissociation pattern is independent of retention delay. We conclude that
      analogous brain regions mediate task-specific retrieval across vastly different
      delays, consistent with the proposal of scale-invariance in episodic memory
      retrieval.

PMID- 25773649
TI  - Implant-based rehabilitation in oncology patients can be performed with high long
      term success.
AB  - PURPOSE: Radiotherapy and compromised vital bone and/or surrounding soft tissue
      can be a challenge to the successful osseointegration of dental implants. We
      evaluated the long-term results of dental implants in patients with oral cancer.
      MATERIALS AND METHODS: To address the research purpose, we designed and
      implemented a retrospective cohort study that included patients with oral cancer
      who had received dental implants from 2003 to 2011. The data were collected from
      a clinical oncology database. The predictor variables included a set of
      heterogeneous variables grouped into logical sets of demographics, surgical
      treatment, dental rehabilitation, radiotherapy type, and tumor entity. The
      primary outcome variable was implant survival; the secondary outcome variable was
      peri-implantitis. The descriptive statistics, survival time analysis, Kaplan
      Meier implant survival curves, and Cox hazard proportional modeling were
      computed. RESULTS: The study sample included 59 patients with oral cancer (20
      women [33.9%], 39 men [66.1%]; mean age at tumor diagnosis, 55 years), who had
      had 272 implants placed during the study period. The mean follow-up period was
      30.9 months (range 3 to 82). Of the 272 implants, 269 (98.9%) and 264 (97.1%) had
      survived for 2 and 5 years, respectively. During the observation period, 10
      implants were lost (3.7%). Of the implant failures, 82% occurred in transplanted
      bone (4 fibula flaps, 4 iliac crests, and 2 native mandibles). We observed peri
      implantitis caused by insufficiently attached gingiva and bone loss in 182 of the
      implants (67%). The factors associated with implant failure were peri
      implantitis, insufficient soft and hard tissue, muscle dysfunction, and
      xerostomia. CONCLUSIONS: Implant-based rehabilitation in oncology patients can
      achieve a high long-term success rate, although risk factors such as impaired
      muscle function and a high frequency of peri-implantitis can affect healing.

PMID- 25773650
TI  - Enchytraeid Reproduction Test(PLUS): hatching, growth and full life cycle test-
      an optional multi-endpoint test with Enchytraeus crypticus.
AB  - Soil ecotoxicity standard tests for invertebrates are usually limited to the
      assessment of endpoints like survival and reproduction. Adverse effects may occur
      at other developmental stages, e.g. embryo development, hatching or growth. The
      species Enchytraeus crypticus is a model organism in the standard soil
      ecotoxicology test, where survival and reproduction are assessed. In the present
      study we optimized the test method to include additional endpoints. The proposed
      test started with synchronized age organisms', and included additionally hatching
      success, growth, maturation status and full life cycle. This allowed for the
      calculation of cocoon production and population growth rate. Results indicated
      that Cd is embryotoxic, main effect occurs on the embryo developmental stage and
      maturity. Further, the full life cycle test can discriminate between pre- and
      post-embryo formation. The increased sensitivity and full life cycle detail level
      makes it potentially useful for novel materials e.g. nanomaterials where the mode
      of action and hence effect target is unknown. 

PMID- 25773651
TI  - Ancient DNA analysis - An established technique in charting the evolution of
      tuberculosis and leprosy.
AB  - Many tuberculosis and leprosy infections are latent or paucibacillary, suggesting
      a long time-scale for host and pathogen co-existence. Palaeopathology enables
      recognition of archaeological cases and PCR detects pathogen ancient DNA (aDNA).
      Mycobacterium tuberculosis and Mycobacterium leprae cell wall lipids are more
      stable than aDNA and restrict permeability, thereby possibly aiding long-term
      persistence of pathogen aDNA. Amplification of aDNA, using specific PCR primers
      designed for short fragments and linked to fluorescent probes, gives good
      results, especially when designed to target multi-copy loci. Such studies have
      confirmed tuberculosis and leprosy, including co-infections. Many tuberculosis
      cases have non-specific or no visible skeletal pathology, consistent with the
      natural history of this disease. M. tuberculosis and M. leprae are obligate
      parasites, closely associated with their human host following recent clonal
      distribution. Therefore genotyping based on single nucleotide polymorphisms
      (SNPs) can indicate their origins, spread and phylogeny. Knowledge of extant
      genetic lineages at particular times in past human populations can be obtained
      from well-preserved specimens where molecular typing is possible, using deletion
      analysis, microsatellite analysis and whole genome sequencing. Such studies have
      identified non-bovine tuberculosis from a Pleistocene bison from 17,500 years BP,
      human tuberculosis from 9000 years ago and leprosy from over 2000 years ago.

PMID- 25773652
TI  - Antagonizing pathways leading to differential dynamics in colon carcinogenesis in
      Shugoshin1 (Sgo1)-haploinsufficient chromosome instability model.
AB  - Colon cancer is the second most lethal cancer. It is predicted to claim 50,310
      lives in 2014. Chromosome Instability (CIN) is observed in 80-90% of colon
      cancers, and is thought to contribute to colon cancer progression and recurrence.
      However, there are no animal models of CIN that have been validated for studies
      of colon cancer development or drug testing. In this study, we sought to validate
      a mitotic error-induced CIN model mouse, the Shugoshin1 (Sgo1) haploinsufficient
      mouse, as a colon cancer study model. Wild-type and Sgo1(-/+) mice were treated
      with the colonic carcinogen, azoxymethane (AOM). We tracked colon tumor
      development 12, 24, and 36 wk after treatment to assess progression of colon
      tumorigenesis. Initially, more precancerous lesions, Aberrant Crypt Foci (ACF),
      developed in Sgo1(-/+) mice. However, the ACF did not develop straightforwardly
      into larger tumors. At the 36-wk endpoint, the number of gross tumors in Sgo1(
      /+) mice was no different from that in wild-type controls. However, Copy Number
      Variation (CNV) analysis indicated that fully developed colon tumor in Sgo1(-/+)
      mice carried 13.75 times more CNV. Immunohistological analyses indicated that
      Sgo1(-/+) mice differentially expressed IL-6, Bcl2, and p16(INK4A) . We propose
      that formation of ACF in Sgo1(-/+) mice is facilitated by the IL6-STAT3-SOCS3
      oncogenic pathway and by the Bcl2-anti-apoptotic pathway, yet further development
      of the ACF to tumors is inhibited by the p16(INK4A) tumor suppressor pathway.
      Manipulating these pathways would be beneficial for inhibiting development of
      colon cancer with CIN.

PMID- 25773653
TI  - Post-surgical therapeutic approaches to glioblastoma patients submitted to biopsy
      (BA) or "partial" resection (PR): the possibilities to treat also them without
      renunciations. Study from the Brescia Neuro-Oncology Group.
AB  - The extent of surgery predicts overall survival (OS) in patients treated for
      glioblastoma (GBM). The therapeutic approach after partial resection (PR) or
      biopsy alone (BA) is not clearly defined. This retrospective analysis was
      therefore planned to analyse clinical features, treatment and survival of
      patients undergoing PR or BA. We analysed the clinical/therapeutic features and
      the outcome of 232 patients submitted to BA/PR and treated with radiotherapy (RT)
      with/without chemotherapy. Two subgroups (pre- and post-Temozolomide-era) were
      identified. The BA/PR ratio did not change with the accrual periods. In the TMZ
      era, 50 % of the patients had chemotherapy; "small" volume, hypo-fractionated and
      "low" dose RT (<54 Gy) were delivered to 93, 38 and 44 % of the patients;
      corresponding values for the previous period were 4, 28, 11 and 2 % (P < 0.001).
      Better two-year OS was evident in the TMZ-era (18 vs 7 %); PR and chemotherapy
      affected OS in patients treated with hypo-fractionated, low doses RT (P = 0.02,
      0.04). Limited volume, more often MRI-based, and "short" RT treatments were given
      mostly to unfavourably selected patients, without compromising the results of the
      whole group. This strategy, combined with an increased use of chemotherapy,
      resulted in reduced treatment burden, in an improved 2-year OS rate and
      prospectively in better quality of life, even in this prognostically worse subset
      of glioma patients. 

PMID- 25773654
TI  - Evaluating changes in tendon crimp with fatigue loading as an ex vivo structural
      assessment of tendon damage.
AB  - The complex structure of tendons relates to their mechanical properties. Previous
      research has associated the waviness of collagen fibers (crimp) during quasi
      static tensile loading to tensile mechanical properties, but less is known about
      the role of fatigue loading on crimp properties. In this study (IACUC approved),
      mouse patellar tendons were fatigue loaded while an integrated plane polariscope
      simultaneously assessed crimp properties. We demonstrate a novel structural
      mechanism whereby tendon crimp amplitude and frequency are altered with fatigue
      loading. In particular, fatigue loading increased the crimp amplitude across the
      tendon width and length, and these structural alterations were shown to be both
      region and load dependent. The change in crimp amplitude was strongly correlated
      to mechanical tissue laxity (defined as the ratio of displacement and gauge
      length relative to the first cycle of fatigue loading assessed at constant load
      throughout testing), at all loads and regions evaluated. Together, this study
      highlights the role of fatigue loading on tendon crimp properties as a function
      of load applied and region evaluated, and offers an additional structural
      mechanism for mechanical alterations that may lead to ultimate tendon failure.

PMID- 25773656
TI  - Reduced dose of tocilizumab for the maintenance of remission in patients with
      rheumatoid arthritis: a clinical experience.

PMID- 25773655
TI  - Patterns of use and dosing of tocilizumab in the treatment of patients with
      rheumatoid arthritis in routine clinical practice: the ACT-LIFE study.
AB  - The aim of the study was to identify and describe the patterns of use of
      tocilizumab in clinical practice to ensure safety and optimal management of
      rheumatoid arthritis (RA). This is a 12-month prospective observational study in
      patients with moderate or severe RA of >=6 months' duration who have started
      tocilizumab after failure of at least one previous disease-modifying
      antirheumatic drug (DMARD) including TNF inhibitors. For some analyses, patients
      were categorized by the use of tocilizumab as monotherapy or in combination, and
      by previous use of biological therapy. Overall, 379 were evaluable (84.4 %
      received tocilizumab after prior biologics and 78.4 % in combination with classic
      DMARDs). Tocilizumab was discontinued in 68/379 (17.9 %) patients after a median
      of 6.7 (3.7-10.4) months, mainly due to a lack of efficacy (24/379, 6.3 %) and
      adverse events (23/379, 6.1 %). Of 131 temporary interruptions of tocilizumab
      required in 101/379 (26.6 %) patients, 81/131 (61.8 %) were related to adverse
      events, and in 120/131 (91.6 %) cases, tocilizumab was reintroduced at 8 mg/kg.
      Thirty-six tocilizumab dose reductions occurred in 34/379 (9 %) patients due to
      abnormal laboratory values in 20/34 (55.6 %) cases. DAS28-ESR scores decreased
      from baseline (5.6 +/- 1.0) to week 24 (3.0 +/- 1.4) and week 52 (2.7 +/- 1.3).
      DAS28 response differed between biologics-naive and biologics-experienced
      patients, both at weeks 24 and 52. In clinical practice, tocilizumab is effective
      in RA while retaining the expected safety and tolerability profile. Tocilizumab
      seems to be more effective for biologics-naive patients than for biologics
      experienced patients, while it proves to be similarly effective when used in
      combination or monotherapy.

PMID- 25773657
TI  - Vitamin D status in Egyptian patients with juvenile-onset systemic lupus
      erythematosus.
AB  - There are scanty data on the prevalence of vitamin D deficiency and its relation
      to disease activity among patients with juvenile-onset systemic lupus
      erythematosus (JoSLE) in the Middle East and North Africa, an area known to be
      endemic for vitamin D deficiency and insufficiency. The aim of this study was,
      therefore, to study vitamin D status and its relation to disease activity and
      parameters in Egyptian patients with JoSLE. Serum levels of 25(OH) D3 in 70 JoSLE
      patients were compared to 40 age-, sex-, and body mass index-matched healthy
      controls. The 25(OH) D3 was determined by enzyme-linked immunosorbent assay.
      Information regarding the medical history, clinical symptoms, and signs was
      registered at the time of serum sampling. Disease activity of SLE was evaluated
      according to the SLEDAI score. The mean level of serum 25(OH) D3 was 12 +/- 3.7
      in JoSLE patients compared to 21 +/- 3.5 ng/mL in normal controls (p < 0.001).
      Forty percent (28/70) of the JoSLE patients has severe 25(OH) D3 deficiency (<=10
      ng/mL), and 60 % of the JoSLE patients has 25(OH) D3 insufficiency (<=30 ng/mL).
      None of the JoSLE patients has 25(OH) D3 level >30 ng/mL. There was no
      significant correlation between serum levels of 25(OH) D3 and the demographic
      data, medication used, and some laboratory data of patients with JoSLE. Disease
      activity score in our patients was insignificantly correlated with serum levels
      of 25(OH) D3. In spite of vitamin D supplementation in Egyptian JoSLE patients
      and the presence of vitamin D insufficiency in the control group, there are still
      significantly lower levels of vitamin D in JoSLE compared to normal controls.

PMID- 25773658
TI  - Increased detection of latent tuberculosis by tuberculin skin test and booster
      phenomenon in early rheumatoid arthritis patients.
AB  - The incidence of tuberculosis (TB) in rheumatoid arthritis (RA) patients is up to
      four times higher when compared to the general population, but their risk
      increases with the use of TNF-a drugs. Appropriate screening of latent
      tuberculosis infection (LTBI) and proper management of such cases substantially
      reduce the incidence of active TB. Tuberculin skin test (TST) is a widely used
      method for the detection of LTBI. The time of diagnosis of RA as well as the age
      of the patient might modify the TST performance. We did an observational,
      comparative study of RA patients with early and established disease, with the
      objective to know the prevalence of LTBI using the TST and booster test; an
      induration >=5 mm was considered reactive. We evaluated 143 patients (83 [58 %]
      early RA patients). We found 31.3 and 21.7 % TST positivity in early and
      established RA patients, respectively. With the use of booster test, the
      positivity increased to 46.5 and 28.8 %, respectively (p = 0.048, OR 1.33, 95 %
      CI 1.01-1.75). In conclusion, we found that TST and booster test increased LTBI
      detection in early RA patients, which may suggest that time of RA diagnosis might
      affect cellular immunity and therefore the TST response.

PMID- 25773659
TI  - Prevalence of ankylosing spondylitis in Poland and costs generated by AS patients
      in the public healthcare system.
AB  - The aim of the research was to analyse the prevalence of ankylosing spondylitis
      (AS) in Poland and to assess the costs generated by AS patients in the system of
      public health care. The database of national payer-National Health Fund (NHF)-has
      been analysed. For the analysis, the information has been extracted from IT
      system about each treated patient with ICD-10 = M45 code as main or coexisting
      diagnosis included in the mandatory reports from entities of public healthcare
      service. In the years 2008-2013, from 28,800 to 32,800 persons diagnosed with AS
      as main or coexisting diagnosis have been registered in NHF database. In 2013,
      the prevalence amounted to 7.48 for 10,000 persons of general population-the
      highest in Kujawy-Pomerania province (10.92 per 10,000 inhabitants), Silesia
      (10.04) and Swietokrzyskie province (9.81). In male patients, this coefficient
      amounted to 8.91 per 10,000 inhabitants, whereas in female-to 6.15. In 2013, the
      prevalence for men was the highest in the age group of 60-64 years and for women
      in the group of 65-69 years. The healthcare expenses related to AS financed by
      the NHF increased from 13,200 million PLN (6.3 million USD) in 2008 to 72,600
      million PLN (21,900 million USD) in 2013. The increase in healthcare expenses
      related to AS patients in the public healthcare system is significant and
      noticeable. High regional diversity is also a vital issue. It is necessary to
      carry out further research on the incidence rate of AS in Polish population. 

PMID- 25773661
TI  - The Speed of Visual Attention and Motor-Response Decisions in Adult Attention
      Deficit/Hyperactivity Disorder.
AB  - BACKGROUND: Adults with attention-deficit/hyperactivity disorder (ADHD) exhibit
      slowed reaction times (RTs) in various attention tasks. The exact origins of this
      slowing, however, have not been established. Potential candidates are early
      sensory processes mediating the deployment of focal attention, stimulus response
      translation processes deciding upon the appropriate motor response, and motor
      processes generating the response. METHODS: We combined mental chronometry (RT)
      measures of adult ADHD (n = 15) and healthy control (n = 15) participants with
      their lateralized event-related potentials during the performance of a visual
      search task to differentiate potential sources of slowing at separable levels of
      processing: the posterior contralateral negativity (PCN) was used to index focal
      attentional selection times, while the lateralized readiness potentials
      synchronized to stimulus and response events were used to index the times taken
      for response selection and production, respectively. To assess the clinical
      relevance of event-related potentials, a correlation analysis between neural
      measures and subjective current and retrospective ADHD symptom ratings was
      performed. RESULTS: ADHD patients exhibited slower RTs than control participants,
      which were accompanied by prolonged PCN and lateralized readiness potentials
      synchronized to stimulus, but not lateralized readiness potentials synchronized
      to response events, latencies. Moreover, the PCN timing was positively correlated
      with ADHD symptom ratings. CONCLUSIONS: The behavioral RT slowing of adult ADHD
      patients was based on a summation of internal processing delays arising at
      perceptual and response selection stages; motor response production, by contrast,
      was not impaired. The correlation between PCN times and ADHD symptom ratings
      suggests that this brain signal may serve as a potential candidate for a
      neurocognitive endophenotype of ADHD.

PMID- 25773660
TI  - TGF-beta signal transduction pathways and osteoarthritis.
AB  - Osteoarthritis (OA) is the most common form of arthritis, resulting in
      substantial disability and economic burden worldwide. While its exact
      pathogenesis remains elusive, both in vitro and human population-based studies
      have merged to support the hypothesis that TGF-beta/BMP-mediated signalling
      pathways play a role in the development of OA. Unraveling the TGF-beta/BMP
      mediated mechanism(s) in OA has great potential in identifying novel targets and
      developing new drugs for OA treatment. This review summarizes both in vitro and
      in vivo evidence of TGF-beta/BMP-mediated signal transduction pathways in OA and
      discusses the future research direction in this regard. 

PMID- 25773662
TI  - Gaps Between Aims and Achievements in Therapeutic Modification of Neuronal Damage
      ("Neuroprotection").
AB  - The term "neuroprotection" is often misused, overused, or misunderstood. A
      reasonable definition of neuroprotection refers to the preservation of "neuronal
      structure and/or function." Although our knowledge about the cellular and
      molecular mechanisms of neurodegeneration has expanded, experimental systems and
      animal models that mimic the process or allow translation into clinical success
      remain limited. This editorial discusses reasons for this gap and strategies to
      close it. Experimental models can only mirror certain aspects of disease
      mechanisms in humans. Therefore, findings in these models need to be linked with
      patient data to improve real-life relevance. Successful neuroprotection depends
      on finding the right "window of opportunity" which varies from very short
      (stroke) to very long (Alzheimer's disease), necessitating the need to focus on
      strategies for very early disease recognition. This need challenges the
      strategies to be chosen, trial approaches and methodologies, and the allocation
      of resources. Additionally, outcome measures are often not well suited to assess
      neuroprotection. To this end, surrogate measures, including biomarkers, are
      useful endpoints to demonstrate evidence of target directed therapeutic utility.
      Finally, studies have shown that neuroprotection is not likely to succeed when
      targeting only one pathway. These obstacles have reduced the level of enthusiasm
      for neuroprotection in certain disease areas (e.g., stroke). Academia, industry,
      regulatory authorities, funding agencies and patient organizations have to
      cooperate to a greater extent in order to overcome these impediments and to
      encourage nonclassical concepts. These concepts will be interdisciplinary in
      order to achieve meaningful disease modification. 

PMID- 25773663
TI  - Symptom score change and patient versus doctor satisfaction in overactive bladder
      before and after anti-muscarinic treatment.
AB  - AIMS: To evaluate voiding symptoms and questionnaire score change before and
      after anti-muscarinic treatment and evaluate the correlation of agreement in
      patient and doctor satisfaction after treatment. METHODS: Forty women newly
      diagnosed with overactive bladder (OAB), attending the urogynecology clinic at
      Chulalongkorn Hospital during April-June 2011 were recruited. Tolterodine 4 mg
      orally once daily was given for 4 weeks. A voiding diary and Thai version of the
      OAB questionnaires eight-item Overactive Bladder awareness tool (OAB-v8),
      Overactive Bladder Symptoms Score (OABSS) and Overactive Bladder QOL (OABq) were
      completed before and at the end of treatment. At the end of the trial, self
      report patient satisfaction, and doctor satisfaction (according to symptom
      improvement in the voiding diary) were assessed. Student's t-test and weighted
      kappa coefficients were used in statistical analysis. Sample size was calculated
      from an OAB questionnaire pilot study with 20% addition for loss to follow up.
      RESULTS: All voiding parameters and questionnaire scores (OAB-v8, OABSS and OABq)
      were improved after treatment. Weighted kappa was only 0.06, between doctor and
      patient satisfaction. CONCLUSION: OAB-v8 and OABSS questionnaires can be used as
      screening and follow-up tools. There is poor agreement between patient and doctor
      satisfaction. Satisfaction should therefore be measured from the patient's
      perspective.

PMID- 25773665
TI  - Favoured local structures in liquids and solids: a 3D lattice model.
AB  - We investigate the connection between the geometry of Favoured Local Structures
      (FLS) in liquids and the associated liquid and solid properties. We introduce a
      lattice spin model - the FLS model on a face-centered cubic lattice - where this
      geometry can be arbitrarily chosen among a discrete set of 115 possible FLS. We
      find crystalline groundstates for all choices of a single FLS. Sampling all
      possible FLS's, we identify the following trends: (i) low symmetry FLS's produce
      larger crystal unit cells but not necessarily higher energy groundstates, (ii)
      chiral FLS's exhibit peculiarly poor packing properties, (iii) accumulation of
      FLS's in supercooled liquids is linked to large crystal unit cells, and (iv) low
      symmetry FLS's tend to find metastable structures on cooling. 

PMID- 25773664
TI  - Inhibitory effects of interferon-beta on hepatocellular carcinoma HepG2 via
      Akt/STAT phosphorylation.
AB  - Conventional chemotherapy fails to cure metastatic hepatoma mainly due to its
      high hepatotoxicity. Currently, doxorubicin is the most widely used drug against
      liver cancer either as single agent or in combination with other
      chemotherapeutics such as cisplatin. It is limited due to their severe toxicity
      on normal hepatocytes. Therefore, alternative therapeutic agents without or with
      low hepatotoxicity are highly desirable. Interferons are a family of cytokines
      that potently demonstrate antiviral, immunomodulatory, and antiproliferative
      activities. It also exerts direct cytotoxic effects on tumor cells. The purpose
      of this study was to examine the in vitro cytotoxicity of interferon-beta on
      HepG2 cells. We revealed the presence of binding receptor of interferon-beta in
      HepG2 cells. The dose-dependent inhibition on cell proliferation was observed. We
      demonstrated that IFN-beta exhibited significant cytotoxicity in HepG2 cells
      mainly through phosphorylation of signal transducers and activators of
      transcription 2. The activation of Akt was suppressed. The stimulation of pro
      apoptotic protein expression of Bax, inhibition of anti-apoptotic protein
      expression of Bcl-2, activation of cleaved caspases 9 and 3 was found at
      increasing concentrations. In conclusion, our results suggest that interferon
      beta has potential to inhibit cell proliferation dose dependently. Increased
      concentrations of interferon-beta influenced apoptosis via mitochondrial pathway
      through inhibition of p-Akt. 

PMID- 25773666
TI  - Acteoside attenuates TSLP-induced mast cell proliferation via down-regulating
      MDM2.
AB  - Acteoside (verbascoside) is extensively distributed in Abeliophyllum distichum
      and has antimicrobial and anti-inflammatory properties. Thymic stromal
      lymphopoietin (TSLP) has a pivotal function in the pathogeneses of inflammatory
      diseases through increasing the mast cell proliferation via the activation of
      murine double minute 2 (MDM2). Here, we investigate whether acteoside attenuates
      the MDM2 expression in a TSLP-stimulated human mast cell line (HMC-1 cells). In
      these cells, TSLP induced the up-regulation of MDM2 and the down-regulation of
      p53; however, in the TSLP-stimulated HMC-1 cells, the acteoside down-regulated
      the MDM2 and up-regulated the p53. Increases in the phosphorylation of the single
      transducer and activation of transcription 6 and 5 via TSLP are decreased by
      acteoside. The interleukin (IL)-13 (a mast cell growth factor), IL-6, tumor
      necrosis factor-alpha, and IL-1beta levels are significantly reduced by the
      acteoside in the TSLP-stimulated HMC-1 cells, and the acteoside significantly
      induces the activation of caspase-3, the cleavage of poly-ADP-ribose polymerase,
      and the reduction of the procaspase-3 and Bcl2. Furthermore, the mRNA expressions
      of the TSLP receptor and IL-7 receptor that increase due to TSLP are reduced by
      the acteoside. In conclusion, these results indicate that acteoside is a specific
      regulator of MDM2 activation in TSLP-stimulated mast cells, which indicates its
      potential use for the treatment of mast cell-mediated inflammatory diseases.

PMID- 25773667
TI  - Sca1(+) mesenchymal stromal cells inhibit graft-versus-host disease in mice after
      bone marrow transplantation.
AB  - Mesenchymal stromal cells (MSCs) have therapeutic potential for the prevention
      and treatment of graft-versus-host disease (GVHD). However, MSCs comprise several
      subpopulations, which have not been individually assessed for their role in GVHD
      suppression. In this study, we assessed the immunosuppressive effect of bone
      related Sca1(+) MSCs on acute GVHD in a MHC-mismatched mouse model of allogeneic
      hematopoietic stem cell transplantation (HCT). Our results showed that Sca1(+)
      MSCs decreased the severity of acute GVHD (aGVHD) and prolonged the survival
      period of allogeneic HCT recipients. This effect was exerted through lowered T
      lymphocyte infiltration in target organs and by inhibition of CD80/86 expression
      on host dendritic cells. Furthermore, the expression of cytotoxic T-lymphocyte
      antigen-4 (CTLA-4), a negative regulator of T cells, was elevated in the
      recipient splenocytes. In conclusion, bone-related Sca1(+) MSCs subpopulation
      suppressed GVHD and could be a novel treatment for acute GVHD.

PMID- 25773668
TI  - The effect of "hands on" techniques on obstetric perineal laceration: A
      structured review of the literature.
AB  - OBJECTIVE: The purpose of this structured review was to review current evidence
      of "hands on" and "hands off" techniques as it relates to rates of perineal
      laceration in order to provide direction for future research in this important
      area of midwifery practice. METHOD: A structured literature search using all
      identified keywords and index terms was undertaken in MEDLINE, EMBASE Joanna
      Briggs Institute, CINAHL, TRIP, and OVID nursing database. FINDINGS: A total of
      24 papers were identified from the initial searches as potentially relevant to
      the review questions. Of these a total of nine papers were considered relevant
      for this review. These nine included one systematic review with meta-analysis,
      four randomised controlled trials (RCTs), one quasi-experimental study and three
      cohort studies. CONCLUSION: "Hands on" techniques have been traditionally used
      but not been well defined in the literature, therefore it is currently unclear as
      to whether or not "hands on" technique can reduce perineal laceration. More
      studies are required to test the effectiveness of a standardised "hands on"
      technique and also to determine what part other factors such as maternal
      position, visualisation and use of water might play in perineal laceration rates.

PMID- 25773669
TI  - Research capacity building in midwifery: Case study of an Australian Graduate
      Midwifery Research Intern Programme.
AB  - BACKGROUND: Having the research capacity to identify problems, create new
      knowledge and most importantly translate this knowledge into practice is
      essential within health care. Midwifery, as well as other health professions in
      Australia, is challenged in building its research capacity to contribute evidence
      to inform clinical practice. AIM: The aim of this project was to evaluate an
      innovative Graduate Midwifery Research Intern Programme offered at a tertiary
      obstetric hospital in Western Australia, to determine what was working well and
      how the programme could be improved. METHOD: A case study approach was used to
      gain feedback from graduate midwives within a Graduate Research Intern (GRI)
      Programme. In addition outcomes were compiled of all projects the GRI midwives
      contributed to. Six GRI midwives participated in a survey comprising of four open
      ended questions to provide feedback about the programme. RESULTS: Findings
      confirm that the GRI programme increased the graduates understanding of how
      research works, its capacity to define a problem, generate new knowledge and
      inform clinical practice. The GRI midwives' feedback suggested the programme
      opened their thinking to future study and gave them enhanced insight into women's
      experiences around childbirth. CONCLUSION: To grow our knowledge as a
      professional group, midwives must develop and promote programmes to build our
      pool of research capable midwives. By sharing our programme evaluation we hope to
      entice other clinical settings to consider the value in replicating such a
      programme within their context.

PMID- 25773670
TI  - Infant mortality and isotopic complexity: New approaches to stress, maternal
      health, and weaning.
AB  - OBJECTIVES: Studies of the carbon and nitrogen stable isotope ratios (delta(13) C
      and delta(15) N) of modern tissues with a fast turnover, such as hair and
      fingernails, have established the relationship between these values in mothers
      and their infants during breastfeeding and weaning. Using collagen from high
      resolution dentine sections of teeth, which form in the perinatal period we
      investigate the relationship between diet and physiology in this pivotal stage of
      life. MATERIALS AND METHODS: Childhood dentine collagen delta(13) C and delta(15)
      N profiles were produced from horizontal sections of permanent and deciduous
      teeth following the direction of development. These were from two 19th-century
      sites (n = 24) and a small number (n = 5) of prehistoric samples from Great
      Britain and Ireland. RESULTS: These high-resolution data exhibit marked
      differences between those who survived childhood and those who did not, the
      former varying little and the latter fluctuating widely. DISCUSSION:
      Breastfeeding and weaning behavior have a significant impact on the morbidity and
      mortality of infants and the adults they become. In the absence of documentary
      evidence, archaeological studies of bone collagen of adults and juveniles have
      been used to infer the prevalence and duration of breastfeeding. These
      interpretations rely on certain assumptions about the relationship between
      isotope ratios in the bone collagen of the adult females and the infants who have
      died. The data from this study suggest a more complex situation than previously
      proposed and the potential for a new approach to the study of maternal and infant
      health in past populations.

PMID- 25773671
TI  - Multicomponent biosurfactants--A "Green Toolbox" extension.
AB  - The unflagging interest in the surfactants of biological origin, representing
      ecological alternatives to their synthetic counterparts, has enhanced R&D effort
      both to produce their new types and to resolve the bottlenecks of their
      commercialization. In this context, the rhamnolipids, offering a relatively large
      scale of potential applications, variety of congeners, low toxicity as well as
      stability towards the extremes of environment, logically attract attention. In
      this connection, the current state of knowledge concerning these compound
      exploitation, biosynthesis control and non-genetic factors affecting both
      production yield and final rhamnolipid product is surveyed. 

PMID- 25773672
TI  - Association of obesity and sleep problems among breast cancer survivors: results
      from a registry-based survey study.
AB  - PURPOSE: Sleep-related complaints are common among breast cancer survivors.
      However, the risk factors underlying sleep disturbances in this population are
      not completely understood. Some studies have shown that maintaining normal weight
      can result in a reduced risk of cancer-related symptoms, including sleep
      problems; however, data from published studies are not consistent. This study
      examined the associations between body mass index (BMI) and sleep-related
      complaints in breast cancer survivors. METHODS: Self-reported survey data from
      861 breast cancer survivors at a single institution were analyzed. BMI was
      calculated based on self-reported weight and height at the time of the survey.
      Daytime sleepiness was assessed using the Epworth Sleepiness Scale. Average sleep
      duration was calculated based on the reported hours of sleep on a typical weekday
      and weekend. Associations between BMI and the sleep outcomes were estimated using
      multivariable logistic regression. RESULTS: In adjusted models, BMI was not
      significantly associated with either excessive daytime sleepiness or "short"
      sleep pattern (<= 6 h) in our sample of breast cancer survivors. Younger age,
      presence of strong acute pain, and lower level of education were independent risk
      factors for excessive daytime sleepiness. African American race, presence of
      strong acute pain, and lower level of education were independent risk factors for
      being a short sleeper. CONCLUSIONS: Findings from this study indicate that BMI is
      not independently associated with sleep-related outcomes among breast cancer
      survivors. More research is needed to identify cancer survivors who are at
      increased risk for sleep disturbances as well as the mechanisms that underlie
      such disturbances.

PMID- 25773674
TI  - Bioactivity of proteins isolated from Lactobacillus plantarum L67 treated with
      Zanthoxylum piperitum DC glycoprotein.
AB  - Lactobacilli in the human gastrointestinal tract have beneficial effects on the
      health of their host. To enhance these effects, the bioactivity of lactobacilli
      can be fortified through exogenous dietary or pharmacological agents, such as
      glycoproteins. To elucidate the inductive effect of Zanthoxylum piperitum DC
      (ZPDC) glycoprotein on Lactobacillus plantarum L67, we evaluated the radical
      scavenging activity, anti-oxidative enzymes (SOD, GPx and CAT), growth rate,
      ATPase activity and beta-galactosidase activity of this strain. When Lact.
      plantarum L67 was treated with ZPDC glycoprotein at different concentrations, the
      intensities of a few SDS-PAGE bands were slightly changed. The amount of a 23 kDa
      protein was increased upon treatment with increasing concentrations of ZPDC
      glycoprotein. The results of this study indicate that the radical-scavenging
      activity for O2(-) and OH-, but not for the DPPH radical, increased in a
      concentration-dependent manner after treatment with ZPDC glycoprotein. The
      activation of anti-oxidative enzymes (SOD, GPx and CAT), growth rate and beta
      galactosidase activity also increased in a concentration-dependent manner in
      response to ZPDC glycoprotein treatment, whereas ATPase activity was decreased.
      In summary, ZPDC glycoprotein stimulated an increase in the bioactivity of Lact.
      plantarum L67. Significance and impact of the study: This study demonstrated that
      Lactobacillus plantarum L67 possesses anti-oxidative activity. This strain of
      lactic bacteria has been known to have various probiotic uses, such as yogurt
      starters and dietary additional supplements. We found, through this experiment,
      that the protein has a strong anti-oxidative character, and the activity can be
      enhanced by treatment with Zanthoxylum piperitum DC (ZPDC) glycoprotein. This
      study may be application of Lact. plantarum L67 treated by ZPDC glycoprotein in
      yogurt fermentation. It could be one of the avenues of minimizing yogurt
      postacidification during storage. In addition, it can be manufactured and
      incorporated in food products without losing viability and functionality of Lact.
      plantarum L67.

PMID- 25773673
TI  - Economic and clinical aspects of intravenous versus oral busulfan in adult
      patients for conditioning prior to HSCT.
AB  - PURPOSE: Busulfan (BU) used as cytoreductive conditioning prior to hematopoietic
      stem cell transplantation (HSCT) is available as intravenous (IV) and oral (O)
      preparation. IV-BU has clinical advantages associated with relevant incremental
      costs. The aim was to determine the economic impact of IV-BU versus O-BU in adult
      HSCT recipients from a German health care providers' perspective. METHODS: A
      budget-impact model (BIM) including costs and risks for oral mucositis (OM),
      infection with OM, and hepatic sinusoidal obstruction syndrome (SOS) was
      developed. Model inputs are literature data comparing clinical effects of IV-BU
      versus O-BU and German cost data (conditioning therapy, treatment of OM,
      infections, SOS without/with multiorgan failure) from literature and tariff
      lists. RESULTS: Base case calculations resulted the following: total costs of
      adverse events were ?86,434 with O-BU and ?44,376 with IV-BU for ten patients
      each. Considering costs of adverse events and drugs, about ?5840 for ten patients
      receiving IV-BU are saved. Sensitivity analyses were conducted in several ways.
      Cost savings range between ?4910 and ?12,640 per ten patients for all adverse
      events and ?2070 or ?1140 per ten patients considering SOS only. Drug treatment
      of SOS and treatment of multiorgan failure during severe SOS are major cost
      drivers. Worst case scenario calculations (assuming -25% risk of all adverse
      events for O-BU and +25% for IV-BU) yield up to ?27,570 per ten patients with IV
      BU. CONCLUSIONS: Considering costs of adverse events and drugs, IV-BU is the
      dominant alternative from a German providers' perspective. For more comprehensive
      economic evaluations, additional epidemiological data, evidence on clinical
      outcomes, patient-reported outcomes, and treatment patterns are needed.

PMID- 25773676
TI  - Frequency and predictors of seasonal influenza vaccination and reasons for
      refusal among patients at a large tertiary referral hospital.
AB  - We assessed frequency and predictors of seasonal influenza vaccination acceptance
      among inpatients at a large tertiary referral hospital, as well as reasons for
      vaccination refusal. Over 5 seasons, >60% of patients unvaccinated on admission
      refused influenza vaccination while hospitalized; "believes not at risk" was the
      reason most commonly given.

PMID- 25773675
TI  - CHIP stabilizes amyloid precursor protein via proteasomal degradation and p53
      mediated trans-repression of beta-secretase.
AB  - In patient with Alzheimer's disease (AD), deposition of amyloid-beta Abeta, a
      proteolytic cleavage of amyloid precursor protein (APP) by beta-secretase/BACE1,
      forms senile plaque in the brain. BACE1 activation is caused due to oxidative
      stresses and dysfunction of ubiquitin-proteasome system (UPS), which is linked to
      p53 inactivation. As partial suppression of BACE1 attenuates Abeta generation and
      AD-related pathology, it might be an ideal target for AD treatment. We have shown
      that both in neurons and in HEK-APP cells, BACE1 is a new substrate of E3-ligase
      CHIP and an inverse relation exists between CHIP and BACE1 level. CHIP inhibits
      ectopic BACE1 level by promoting its ubiquitination and proteasomal degradation,
      thus reducing APP processing; it stabilizes APP in neurons, thus reducing Abeta.
      CHIP(U) (box) domain physically interacts with BACE1; however, both U-box and TPR
      domain are essential for ubiquitination and degradation of BACE1. Further, BACE1
      is a downstream target of p53 and overexpression of p53 decreases BACE1 level. In
      HEK-APP cells, CHIP is shown to negatively regulate BACE1 promoter through
      stabilization of p53's DNA-binding conformation and its binding upon 5' UTR
      element (+127 to +150). We have thus discovered that CHIP regulates p53-mediated
      trans-repression of BACE1 at both transcriptional and post-translational level.
      We propose that a CHIP-BACE1-p53 feedback loop might control APP stabilization,
      which could further be utilized for new therapeutic intervention in AD.

PMID- 25773677
TI  - Protease-activated receptor 2 enhances renal cell carcinoma cell invasion and
      migration via PI3K/AKT signaling pathway.
AB  - Protease-activated receptor 2 (PAR-2) has been implicated in the regulation of
      several cellular functions in the progression of cancer. It is reported that PAR
      2 expression is significantly increased in human renal cell carcinoma (RCC)
      tissue compared with the adjacent non-neoplastic kidney tissue. However, the
      function of PAR-2 in regulating cell invasion and migration of RCC remains
      elusive. In this study, we found that PAR-2 was overexpressed in RCC cells.
      Activation of PAR-2 with PAR-2AP (PAR-2 agonist) enhanced the invasion and
      migration of RCC cells, and increased the expressions of MMP-13 and urokinase
      plasminogen activator (uPA). However, knockdown of PAR-2 by siRNA could intervene
      in all regulating effects of PAR-2AP. Furthermore, activation of PAR-2 induced
      the activation of PI3K and AKT, and PI3K/AKT inhibitor LY294002 attenuated the
      invasion and migration of RCC cells stimulated by PAR-2 activation. Altogether,
      our study demonstrates that PAR-2 stimulates the activation of PI3K/AKT pathway,
      subsequently increasing the expressions of MMP-13 and uPA, and thereby promotes
      the invasion and migration of RCC cells. 

PMID- 25773678
TI  - Genetic alterations of PIK3CA and tumor response in patients with locally
      advanced cervical squamous cell carcinoma treated with cisplatin-based concurrent
      chemoradiotherapy.
AB  - OBJECTIVE: The objective of this study was to investigate the predictive value of
      common genetic alterations of PI3K/AKT/mTOR and Ras/Raf/MAPK pathways in patients
      with locally advanced cervical squamous cell carcinoma (LACSCC) treated with
      cisplatin-based concurrent chemoradiotherapy (CCRT). METHODS: Patients with
      LACSCC, treated at a single institution with CCRT were eligible for this
      retrospective study. A total of sixty pre-treatment tumor biopsies were
      retrieved. Somatic mutations were detected by pyrosequencing and CNV was
      determined by quantitative realtime PCR. The association of genetic alterations
      with clinicopathological characteristics and treatment response were analyzed.
      RESULTS: Patients without genetic alterations (mutations or amplification) of
      PIK3CA had a significantly higher response rate than patients with these
      alterations (p=0.006). In the logistic regression analysis, PIK3CA genetic
      alterations retained an independent factor in predicting response to CCRT.
      CONCLUSIONS: Somatic mutations and copy number amplification of PIK3CA were
      associated with response to CCRT in patients with cervical squamous cell
      carcinoma.

PMID- 25773679
TI  - Effect of bone morphogenic protein-7 on the expression of epithelial-mesenchymal
      transition markers in silicosis model.
AB  - This study presented the effect of bone morphogenic protein-7 (BMP-7) inhibiting
      epithelial-mesenchymal transition (EMT) in silicosis model. In vivo, Wistar rats
      were exposed to silica by intratracheal instillation. Seven days later rats were
      treated with BMP-7. Rats were sacrificed at 15 and 30days after exposure of
      silica. The results demonstrated vimentin expression was down-regulated; and E
      cadherin was up-regulated after intervention with BMP-7. The TGF-beta expression
      and phosphorylation-p38 were lower in BMP-7 treated group than in silica group.
      In vitro, p38 MAPK/Snail signaling pathway was involved in the occurrence of EMT
      in A549 cells treated by silica. EMT was inhibited by BMP-7. The data showed BMP
      7 inhibited EMT induced by silica associated with inhibition of p38 MAPK/Snail
      pathway. 

PMID- 25773680
TI  - Hypermethylation of potential tumor suppressor miR-34b/c is correlated with late
      clinical stage in patients with soft tissue sarcomas.
AB  - Soft tissue sarcomas (STSs) are comparatively rare malignant tumors with poor
      prognosis. STSs predominantly arise from mesenchymal differentiation. MicroRNA
      34b/c, the transcriptional targets of tumor suppressor p53, possesses tumor
      suppressing property. Hypermethylation of miR-34b/c has been associated with
      tumorigenesis and the progression of various cancers. To determine whether
      aberrant miR-34b/c methylation occurs in STSs, we quantitatively evaluated the
      methylation level of miR-34b/c in 57 STS samples and 20 cases of peripheral blood
      from healthy volunteers serving as normal controls by using matrix-assisted laser
      desorption ionization time-of-flight mass spectrometry. We found that miRNA34b/c
      is more frequently methylated in STSs (0.157+/-0.028) than in normal controls
      (0.098+/-0.012, p=0.038). Furthermore, the methylation levels of CpG_1.2.3,
      CpG_4.5.6.7, and CpG_11.12.13 of miR-34b/c were significantly higher in the STS
      group than in the normal control group (p<0.001). No significant differences in
      the methylation levels within miR-34b/c were observed between specific reciprocal
      translocations in STSs and nonspecific reciprocal translocations in STSs (0.146+/
      0.039 vs. 0.168+/-0.035, p>0.05). The methylation levels of miR-34b/c in STSs
      were associated with clinical stage. The methylation levels of CpG_1.2.3,
      CpG_4.5.6.7, CpG_9.10, CpG_11.12.13, and CpG_14 in tumor-stage III/IV tissues
      were significantly higher than those in tumor-stage I/II tissues. Our findings
      indicated that DNA hypermethylation of the miR-34b/c is a relatively common event
      in STSs and is significantly correlated with late clinical stage in patients with
      STSs. Hypermethylation of the miR-34b/c may be pivotal in the oncogenesis and
      progression of STSs and may be a potential prognostic factor for STSs. 

PMID- 25773682
TI  - Angle between the common and internal carotid arteries detected by ultrasound is
      related to intima-media thickness among those with atherosclerotic disease.
AB  - OBJECTIVES: Although carotid artery structural variations have been detected by
      ultrasound, their clinical significance is not fully understood. The objective of
      this study was to determine whether the angle between the common carotid artery
      (CCA) and the internal carotid artery (ICA), designated angle alpha, an
      ultrasound-detectable carotid artery structural variation, is related to carotid
      artery intima-media thickness (IMT), a surrogate marker for carotid
      atherosclerosis. METHODS: As a cross-sectional study, we measured angle alpha in
      routine carotid artery ultrasounds from 176 subjects (130 men) with
      atherosclerotic disease/risk factors that attended Kouseiren Hospital in
      Kagoshima City, Japan between August 2007 and April 2009. We evaluated the
      correlation between the angle alpha and CCA- or ICA-IMT. RESULTS: Angle alpha was
      weakly correlated with age but significantly correlated with ICA-IMT. The
      correlation was stronger in subjects with an ICA-IMT >= 0.5 mm than in those with
      an ICA-IMT < 0.5 mm (Right side r = 0.475 vs. 0.246, Left side r = 0.498 vs.
      0.301, respectively). Upon multivariate logistic regression analysis, angle alpha
      and serum low-density lipoprotein cholesterol were independent explanatory
      variables for ICA-IMT. CONCLUSION: Angle alpha is related to ICA-IMT in subjects
      with atherosclerotic disease or risk factors in this study.

PMID- 25773683
TI  - Effect of a school-based nutrition education program on adolescents' nutrition
      related knowledge, attitudes and behaviour in rural areas of China.
AB  - OBJECTIVES: This study aimed at examining the effect of the nutrition education
      program on adolescents' knowledge, attitudes and behaviour in relation to
      nutrition in rural China. METHODS: A cluster-randomised intervention trial design
      was employed. Two middle schools were randomly selected and assigned to the
      school conducting nutrition education (NE school), or to the Control school, in
      Mi Yun County, Beijing. From each school 65 seventh-grade students were randomly
      selected to participate in the study. Nutrition-related knowledge, attitudes and
      behaviour were measured at pre- and post-intervention surveys with the same
      instrument. The nutrition education lasted for 6 months. RESULTS: After the
      intervention, more students in NE school knew the main function of dairy products
      and vegetables, which micronutrient is rich in dairy products and beans, and in
      meat, and the symptom of food poisoning, than those in Control school. The rate
      of students who thought nutrition is very important to health, and foods with an
      expired date should be thrown away in NE school was higher than that in Control
      school (93.8 vs. 80.3 and 92.3 vs. 78.7%, respectively). The rate of students who
      ate vegetables and breakfast everyday in NE school was higher than that in
      Control school (96.9 vs. 80.3, and 89.2 vs. 75.4%, respectively). (p < 0.05).
      CONCLUSIONS: This nutrition education programme is effective in improving
      adolescents' knowledge, attitudes, and behaviour in relation to nutrition;
      therefore, the nutrition education with interactive and innovative intervention
      components is strongly recommended for future nutrition promotion programmes for
      adolescents.

PMID- 25773684
TI  - Light illuminated alpha-Fe2O3/Pt nanoparticles as water activation agent for
      photoelectrochemical water splitting.
AB  - The photoelectrochemical (PEC) water splitting is hampered by strong bonds of H2O
      molecules and low ionic conductivity of pure water. The photocatalysts dispersed
      in pure water can serve as a water activation agent, which provides an
      alternative pathway to overcome such limitations. Here we report that the light
      illuminated alpha-Fe2O3/Pt nanoparticles may produce a reservoir of reactive
      intermediates including H2O2, .OH, OH(-) and H(+) capable of promoting the pure
      water reduction/oxidation half-reactions at cathode and highly photocatalytic
      active TiO2/In2S3/AgInS2 photoanode, respectively. Remarkable photocurrent
      enhancement has been obtained with alpha-Fe2O3/Pt as water activation agent. The
      use of alpha-Fe2O3/Pt to promote the reactivity of pure water represents a new
      paradigm for reproducible hydrogen fuel provision by PEC water splitting,
      allowing efficient splitting of pure water without adding of corrosive chemicals
      or sacrificial agent.

PMID- 25773686
TI  - Sleep inertia, sleep homeostatic and circadian influences on higher-order
      cognitive functions.
AB  - Sleep inertia, sleep homeostatic and circadian processes modulate cognition,
      including reaction time, memory, mood and alertness. How these processes
      influence higher-order cognitive functions is not well known. Six participants
      completed a 73-day-long study that included two 14-day-long 28-h forced
      desynchrony protocols to examine separate and interacting influences of sleep
      inertia, sleep homeostasis and circadian phase on higher-order cognitive
      functions of inhibitory control and selective visual attention. Cognitive
      performance for most measures was impaired immediately after scheduled awakening
      and improved during the first ~2-4 h of wakefulness (decreasing sleep inertia);
      worsened thereafter until scheduled bedtime (increasing sleep homeostasis); and
      was worst at ~60 degrees  and best at ~240 degrees  (circadian modulation, with
      worst and best phases corresponding to ~09:00 and ~21:00 hours, respectively, in
      individuals with a habitual wake time of 07:00 hours). The relative influences of
      sleep inertia, sleep homeostasis and circadian phase depended on the specific
      higher-order cognitive function task examined. Inhibitory control appeared to be
      modulated most strongly by circadian phase, whereas selective visual attention
      for a spatial-configuration search task was modulated most strongly by sleep
      inertia. These findings demonstrate that some higher-order cognitive processes
      are differentially sensitive to different sleep-wake regulatory processes.
      Differential modulation of cognitive functions by different sleep-wake regulatory
      processes has important implications for understanding mechanisms contributing to
      performance impairments during adverse circadian phases, sleep deprivation and/or
      upon awakening from sleep. 

PMID- 25773688
TI  - Health status and quality of life in patients with psoriasis: an Iranian cross
      sectional survey.
AB  - BACKGROUND: Psoriasis has a significant negative impact on patients' health
      related quality of life (HRQOL). This study aims to evaluate HRQOL of adult
      patients with psoriasis in Iran, and explore the relationship between general and
      disease-specific outcome measures in psoriasis. METHODS: Between May and August
      2013, a cross-sectional questionnaire survey of consecutive outpatients was
      conducted at a single clinic in Shiraz, Iran. HRQOL was assessed by the general
      measure EuroQol 5 dimensions (EQ-5D), visual analogue scale (EQ VAS), and the
      disease-specific Dermatology Life Quality Index (DLQI). Disease severity was
      measured by the Psoriasis Area and Severity Index (PASI). RESULTS: Sixty-two
      patients (76% males) completed the questionnaire with a mean age (SD) of 40.4
      (17.5) years. Overall, 39% of the patients used only topical and 48% received
      systemic non-biological therapy in the past 12 months. Median EQ-5D, EQ VAS, DLQI
      and PASI scores were 0.73, 60, 8 and 11.75, respectively. Out of the 62 patients,
      18%, 26%, 28%, 63%, and 63% reported some or severe problem in mobility, self
      care, usual activities, pain/discomfort and anxiety/depression, respectively. EQ
      5D and EQ VAS correlated moderately with DLQI (rs = -0.44 for both, p < 0.001),
      but only EQ VAS correlated significantly with PASI (rs = -0.31, p < 0.01).
      CONCLUSION: This is the first study from Iran that assesses HRQOL in adult
      patients with psoriasis by EQ-5D and EQ VAS. Reduction in general HRQOL measured
      with EQ-5D and EQ-VAS is considerable, mostly in anxiety/depression and
      pain/discomfort dimensions. EQ-5D scores evaluated in this study provide country
      specific data for economic evaluations.

PMID- 25773687
TI  - Cardiovascular disease mortality and years of life lost attributable to non
      optimal systolic blood pressure and hypertension in northeastern Iran.
AB  - BACKGROUND: High blood pressure is the second most important risk factor of
      cardiovascular diseases (CVDs) in Iran. It is imperative to estimate the burden
      of CVDs that can be averted if high blood pressure is controlled at the
      population level. The aim of the current study was to estimate the avertable CVD
      mortality in the setting of Golestan Cohort Study (GCS). METHODS: Over 50,000
      participants were recruited and followed for a median of 7 years. The exposures
      of interest in this study were non-optimal systolic blood pressure (SBP) and
      hypertension measured at baseline. Deaths by cause have been precisely recorded.
      The Population Attributable Fraction (PAF) of deaths and Years of Life Lost
      (YLLs) due to CVDs attributable to exposures of interest were calculated.
      RESULTS: Overall, 223 deaths due to ischemic heart disease (IHD), 207 deaths due
      to cerebrovascular accidents (CVA), and 460 deaths due to all CVDs could be
      averted if the SBP of all subjects in the study were optimal. Similarly, 5,560
      YLLs due to IHD, 4,771 YLLs due to CVA, and 11,135 YLLs due to CVDs could be
      prevented if SBP were optimal. In all age groups, the avertable deaths and YLLs
      were higher due to IHD compared with CVA. Deaths and YLLs attributable to non
      optimal SBP in women were less than men. CONCLUSIONS: A very large proportion of
      CVD deaths can be averted if blood pressure is controlled in Iran. Effective
      interventions in primary and secondary health care setting are mandatory to be
      implemented as early as possible.

PMID- 25773689
TI  - Completeness and underestimation of cancer mortality rate in Iran: a report from
      Fars Province in southern Iran.
AB  - BACKGROUND: The incidence and mortality rates of cancer are increasing worldwide,
      particularly in the developing countries. Valid data are needed for measuring the
      cancer burden and making appropriate decisions toward cancer control. We
      evaluated the completeness of death registry with regard to cancer death in Fars
      Province, I. R. of Iran. METHODS: We used data from three sources in Fars
      Province, including the national death registry (source 1), the follow-up data
      from the pathology-based cancer registry (source 2) and hospital based records
      (source 3) during 2004 - 2006. We used the capture-recapture method and estimated
      underestimation and the true age standardized mortality rate (ASMR) for cancer.
      We used log-linear (LL) modeling for statistical analysis. RESULTS: We observed
      1941, 480, and 355 cancer deaths in sources 1, 2 and 3, respectively. After data
      linkage, we estimated that mortality registry had about 40% underestimation for
      cancer death. After adjustment for this underestimation rate, the ASMR of cancer
      in the Fars Province for all cancer types increased from 44.8 per 100,000 (95%
      CI: 42.8 - 46.7) to 76.3 per 100,000 (95% CI: 73.3 - 78.9), accounting for 3309
      (95% CI: 3151 - 3293) cancer deaths annually. CONCLUSION: The mortality rate of
      cancer is considerably higher than the rates reported by the routine registry in
      Iran. Improvement in the validity and completeness of the mortality registry is
      needed to estimate the true mortality rate caused by cancer in Iran.

PMID- 25773690
TI  - Effects of probiotic Lactobacillus acidophilus and Lactobacillus casei on
      colorectal tumor cells activity (CaCo-2).
AB  - BACKGROUND: The probiotic microorganisms are live normal flora that provide
      nutritional benefits. When probiotic administered in adequate amounts, they also
      confer a health benefit on the host. Different mechanisms of probiotic effects
      include the following: stimulating the immune system, modifying the composition
      of normal intestinal flora and preventing the carcinogenic activity of fecal
      enzymes. In this study, direct effects of probiotic lactobacilli on tumor cells
      were investigated. METHODS: Supernatants and bacterial extracts of two standard
      Lactobacillus species (L. acidophilus and L. casei) were prepared and CaCo-2
      cells were treated with them. Probiotic effects on cell proliferation, necrosis,
      apoptosis, migration and invasion were assessed. RESULTS: The supernatants of
      Lactobacilli decreased cell proliferation and increased cell apoptosis, however,
      no significant effect on cell necrosis was reported. In contrast, Lactobacilli
      extract, reduced cell proliferation and increased cell apoptosis. Lactobacilli
      extract also led to cell necrosis. Furthermore, both supernatants and cell
      extracts of the probiotic agents resulted in decreased cells' migration and
      invasion. CONCLUSION: In this study, it was shown that Lactobacilli probiotics
      useful effects are not confined to the enhancement of the immune system; however,
      they effectively suppress the malignant phenotypes of colorectal cancer cells.

PMID- 25773691
TI  - Evaluating the miR-302b and miR-145 expression in formalin-fixed paraffin
      embedded samples of esophageal squamous cell carcinoma.
AB  - BACKGROUND: MicroRNAs are involved in key cellular processes regulating, and
      their misregulation is linked to cancer. The miR-302-367 cluster is exclusively
      expressed in embryonic stem and carcinoma cells. This cluster also promotes cell
      reprogramming and stemness process. In contrast, miR-145 is mostly regarded as a
      tumor suppressor, where it regulates cellular functions such as cell division,
      differentiation, and apoptosis. By suppressing the main pluripotency factors
      (OCT4, SOX2, MYC and KLF4), miR-145 silences the self-renewal program in ESCs.
      Therefore, the main aim of this study is to find a potential link between the
      expression level of hsa-miR-302b and hsa-miR-145 with tumor vs. non-tumor as well
      as high-grade vs. low-grade states of the esophageal tissue samples. METHODS: A
      total number of 40 formalin-fixed, paraffin-embedded (FFPE) samples of esophageal
      squamous-cell carcinoma (ESCC) were obtained, and the tumor and marginal non
      tumor areas delineated and punched off by an expert pathologist. Total RNA was
      extracted with Trizol, and cDNA synthesized using the miRCURY LNATM Universal RT
      microRNA PCR Kit. Real-time reverse transcription polymerase chain reaction (RT
      PCR) assays were performed using specific LNA-primers and SYBR Green master mix.
      RESULTS: The expression level of miR-302b failed to show any significant
      difference, neither between tumor and their non-tumor counterparts, nor among
      tumors with different grades of malignancies (p > 0.05). In contrast, miR-145 was
      significantly down regulated in all grades of tumor samples (p < 0.001). However,
      its expression level could not discriminate between different grades of
      malignancy (p > 0.05). CONCLUSION: Our data revealed a significant down
      regulation of miR-145 in ESCC tissue samples. Based on our ROC curve analysis
      data (AUC = 0.74, p < 0.001) miR-145 could be regarded as a potential tumor
      marker for diagnosis of esophageal cancer.

PMID- 25773692
TI  - New evidence for the role of calpain 10 in autosomal recessive intellectual
      disability: identification of two novel nonsense variants by exome sequencing in
      Iranian families.
AB  - BACKGROUND: Knowledge of the genes responsible for intellectual disability,
      particularly autosomal recessive forms, is rapidly expanding. Increasing numbers
      of the gene show great heterogeneity and supports the hypothesis that human
      genome may contain over 2000 causative genes with a critical role in brain
      development. METHODS: Since 2004, we have applied genome-wide SNP genotyping and
      next-generation sequencing in large consanguineous Iranian families with
      intellectual disability, to identify the genes harboring disease-causing
      mutations. The current study paved the way for identification of responsible
      genes in two unrelated Iranian families. RESULTS: We found two novel nonsense
      mutations, p.C77* and p.Q115*, in the calpain catalytic domain of CAPN10, which
      is a cysteine protease known to be involved in pathogenesis of noninsulin
      dependent diabetes mellitus. Another different mutation in this gene
      (p.S138_R139ins5) has previously been reported in an Iranian family. All of these
      patients have common clinical features in spite of specific brain structural
      abnormalities on MRI. CONCLUSIONS: Different mutations in CAPN10 have already
      been found in three independent Iranian families. These results have strongly
      supported the possible role of CAPN10 in human brain development. Altogether, we
      proposed CAPN10 as a promising candidate gene for intellectual disability, which
      should be considered in diagnostic gene panels.

PMID- 25773693
TI  - Waiting time for first outpatient visit in specialty level: assessing the
      provider related factors.
AB  - BACKGROUND: Recently, there is an increased focus on waiting time as a barrier to
      access to treatment in outpatient services. The aim of this study is to determine
      related factors to outpatient waiting time in specialty levels. METHODS: This was
      a cross sectional study. The target population of this study consisted of
      specialist's and subspecialist's offices in Tehran. All the population (5475
      cases) was studied; however 43.4% of them were not accessible. Accessible cases
      consist of 3098 physicians were included. Data gathered by telephone interview
      and analyzed by SPSS. RESULTS: According to the findings, the level of care; type
      of specialty, being a faculty member, and office location was related to waiting
      time (p < 0.001). Waiting time was also correlated with the number of outpatient
      offices and clinics of each physician (rs= 0.11, P < 0.001), as well as office
      working hours per week (rs= -0.18, P < 0.001). CONCLUSION: The estimated waiting
      time was acceptable, but the range of this parameter was too wide. This situation
      was more severe for some specialties and need some consideration. It should be
      considered that this study was restricted to Tehran. Waiting time is likely to be
      higher in other provinces of the country especially in deprived areas.

PMID- 25773694
TI  - Influence of microvesicles in breast cancer metastasis and their therapeutic
      implications.
AB  - Microvesicles are membranous sac structures released from cell surfaces of many
      eukaryotic cells. Their presence in the blood and urine also signify their
      potential use as biomarkers for early detection and diagnosis of different
      diseases. At present, synthesis and release of these vesicles from mammary tumor
      cells and their role in disease progression requires further research. In this
      report, correlation of microvesicles along with breast cancer metastasis has been
      explored. Metastasis is a process of a non-randomized set of events, which begins
      with a loss of cancer cell adhesion at the primary tumor site. Later on, these
      cells invade the surrounding tissue and enter into circulation. After
      compromising host immune response, these cells extravasate and localized at the
      suitable distant site for a secondary growth. Involvement of microvesicles in
      modulating this process has also been observed. Microvesicles released from
      primary cancer cells may carry mRNA, miRNAs, DNA and various proteins. These
      vesicles may also influence multi drug resistance as observed in breast and
      leukemia cancer cell lines. A thorough understanding of microvesicles synthesis
      and their potential implication in metastasis would facilitate the design of
      novel therapeutic approach for breast cancer. 

PMID- 25773695
TI  - Pituitary stalk thickening in a case of langerhans cell histiocytosis.
AB  - A 16-year-old girl was referred for the evaluation of headache exacerbation and
      progressive loss of visual field from one month ago. She also suffered from
      intermittent diarrhea since 12 months ago and secondary amenorrhea, headache,
      weight loss (4 - 5 kg) and weakness from six months ago. She had a history of
      transient polydipsia and excessive urine output during this period. Brain
      Magnetic Resonance Imaging (MRI) reported a 15 x 15 x 9 millimeters mass lesion
      in the sellar region. It was extended to the suprasellar cistern with mild
      compression of the optic chiasm and mild thickening of the pituitary stalk with
      posterior displacement were reported. In an exisional biopsy of pituitary stalk
      lesion, the pathology result was indicative of Langerhans cell histiocytosis
      (LCH). The patient underwent four periods of chemotherapy with prednisolone and
      vinblastin in 28-day intervals followed by one cycle of radiation therapy. In
      three months follow up after treatment the tumor size was reduced, Levothyroxin
      and Prednisolone were tapered, and pituitary hormones were improved.

PMID- 25773696
TI  - Bilateral complex regional pain syndrome in a woman with major depressive
      disorder.
AB  - Complex regional pain syndrome type 1 (CRPS1) refers to a disorder usually caused
      by trauma; it is characterized by pain, swelling, limited range of motion,
      vasomotor instability, skin changes, joint stiffness, and patchy bone
      demineralization. Most often it occurs after trauma. Other etiologies include
      myocardial ischemia, cerebrovascular accidents, infection and emotional stress.
      We report a case of bilateral CRPS1 of the upper extremities in a 52-year-old
      woman suffering from major depressive disorder. She was complaining about her
      hands' stiffness and pain. She also reported swelling of both upper extremities
      and anhydrosis, thickening of the skin and muscle wasting, finger movement
      limitation, contracture of the digits and trophic skin changes. The diagnosis of
      CRPS1 was suspected, according to history, physical examination, radiographic
      changes and bone scintigraphy.

PMID- 25773697
TI  - Hepatic alveolar echinococcosis.
AB  - Alveolar hydatid disease is a highly malignant form of echinococcosis caused by
      the larvae of the cestode echinococcus multilocularis. Alveolar hydatid disease
      always affects the liver and can metastasise to the lung and brain. Early
      diagnosis and precise evaluation of the localization as well as the extent of
      lesions are essential for treatment. In this report, we present ultrasound and
      computed tomography findings in a patient with hepatic alveolar echinococcosis.
      The patient, who was presented with hepatomegaly, jaundice, and an infiltrative
      solid tumor, diagnosed by ultrasound and computed tomography. In contrast to
      hydatid cyst caused by echinococcus granulosus, this is a rare disease in Iran. 

PMID- 25773698
TI  - Photoclinic. Thyroglossal duct carcinoma.

PMID- 25773699
TI  - Theoretical study of the Wittig reaction of cyclic ketones with phosphorus ylide.
AB  - The Wittig reaction of cyclopropanone, cyclobutanone and cyclopentanone with
      phosphorus ylide (Me3P = CH2) in gas phase was investigated computationally at
      B3LYP/6-31G** level of theory. In the Wittig reaction of cyclic ketones, two
      transition states (TS1 and TS2), corresponding to formation and decomposition of
      oxaphosphetane (OP) were located and investigated. Two loosely bound
      intermediates, a reactant complex (RC) and a product complex (PC) were also
      found. In the reaction of cyclopropanone, cyclobutanone and cyclopentanone, two
      oxaphosphetanes (OP1 and OP2) were predicted. OP1 initially formed was converted
      into OP2 by pseudorotation. In contrast to the reactions with cyclobutanone and
      cyclopentanone, an early TS1 was found in the reaction of cyclopropanone. The
      order of first activation energy barrier relative to reactant total energy was
      found to be cyclopropanone (-4.97 kcal mol(-1)) < cyclobutanone (0.30 kcal mol(
      1)) < cyclopentanone (3.60 kcal mol(-1)).

PMID- 25773700
TI  - Environmental polarity induces conformational transitions in a helical peptide
      sequence from bacteriophage T4 lysozyme and its tandem duplicate: a molecular
      dynamics simulation study.
AB  - Our recent molecular dynamics (MD) simulation of an insertion/duplication mutant
      'L20' of bacteriophage T4 lysozyme demonstrated a solvent induced alpha->beta
      transition in a loosely held duplicate helical region, while alpha-helical
      conformation in the parent region was relatively stabilized by its tertiary
      interactions with the neighboring residues. The solution NMR of the parent
      helical sequence, sans its protein context, showed no inherent tendency to adopt
      a particular secondary structure in pure water but showed alpha-helical
      propensity in TFE/water and SDS micelles. In this study we investigate the
      conformational preference of the 'parent' and 'duplicate' sequences, sans the
      protein context, in pure water and an apolar TFE/water solution. Apolar TFE/water
      solution is a model for non-polar protein context. We performed MD simulations of
      the two peptides, in explicit water and 80% (v/v) TFE/water, using GROMOS 53a6
      force field, at 300 K and 1 bar (under NPT conditions). We show that in TFE/water
      mixture, salt bridges are stabilized by apolar TFE molecules and main chain-main
      chain hydrogen bonds promote the alpha-helical conformation, particularly in the
      duplicate peptide. Solvent exposure, in pure water, resulted in an alpha->beta
      transition to form a triple stranded beta-sheet structure in the 'duplicate'
      sequence, with a rare psi-loop topology, while a mixture of turn/bend
      conformations were adopted by the 'parent' sequence. Thus the differences in
      conformational preference of the parent and duplicate sequence sans protein
      context, in pure water and TFE/water, implicate the importance of the environment
      polarity in dictating the peptide conformation. Mechanism of folding of the
      observed psi-loop in the duplicate sequence gives insights into folding of this
      rare beta-sheet topology.

PMID- 25773701
TI  - Theoretical study of the mechanism of highly diastereoselective formation of a
      strained 3-azabicyclo[3.2.0]heptane derivative.
AB  - The mechanism of multicomponent reactions, especially stereoselective ones is of
      special importance in organic synthesis. The mechanism of diastereoselective
      formation of a highly strained 3-azabicyclo[3.2.0]heptane derivative through a
      catalyst-free multistep reaction is studied by DFT calculations in solution
      phase. The calculations on the two proposed mechanisms (pathways A and B) showed
      that the iminium ion, the relatively high energy species is not the approprite
      reaction intermediate. On the other hand, the lower activation energy of pathway
      B, as compared to that of pathway A, makes it as the preferred mechanism. The
      high stereoselectivity of the stepwise reaction may be attributed to the fact
      that the rate limiting and stereodifferentiating steps are the same. These
      findings may also account the formation of by-product in the experimental
      observations. 

PMID- 25773702
TI  - Trace Elements in the Marine Sediments of the La Paz Lagoon, Baja California
      Peninsula, Mexico: Pollution Status in 2013.
AB  - To determine the actual concentrations of trace elements in surface sediments
      from the La Paz Lagoon, as well as their associations and possible origins, 91
      sediment samples were analyzed for more than 50 elements using a combination of
      ICP-MS and ICP-AES. The results of a principal component analysis are used to
      distinguish four associative groups within the elements. Natural enrichment of
      As, Cd and U occurs due to the supply of weathered phosphorites from the El Cien
      formation located to the north-west of the lagoon. Sediment quality indices for
      potentially toxic trace elements do not show any probable impact on the biota of
      the lagoon. Only the concentrations of As in 30 % of the stations and Cu in 20 %
      of them exceed related effect range low levels. The highest concentration of Pb
      (36.8 mg kg(-1)) was measured in the sediments near the City of La Paz.

PMID- 25773703
TI  - Monitoring of pesticide residues in human blood from Punjab, India.
AB  - In the present study, the current levels of pesticide residues were studied in
      the human populace of Punjab state. A total of 111 human blood samples were
      analyzed by gas chromatography and pesticide residues were detected in 35 % of
      the blood sample(s). Residues of alpha-hexachlorocyclohexane (alpha-HCH), beta
      hexachlorocyclohexane (beta-HCH), p,p'-dichlorodiphenyldichloroethane (p,p' DDD),
      p,p' dichlorodiphenyldichloroethylene (p,p' DDE), p,p'
      dichlorodiphenyldichloroethane (p,p' DDT), beta-endosulfan, monocrotophos,
      profenophos and phosalone were found in human blood samples with mean levels of
      1.11, 5.89, 0.51, 3.88, 0.39, 34.90, 0.79, 0.39 and 6.76 ng ml(-1), respectively,
      with beta-endosulfan as a leading pesticide residue. A paradigm shift in the
      pattern of the pesticide usage was observed with a shift from organochlorine
      pesticides to organophosphates.

PMID- 25773704
TI  - Characterization of bone turnover and energy metabolism in a rat model of primary
      and secondary osteoporosis.
AB  - BACKGROUND: An experimental rat model served for evaluation of bone- and energy
      metabolism in early and late stages of osteoporosis. For the early stage, we
      hypothesized that bilateral ovariectomy (OVX)+multi-deficiency diet (OVXD;
      depletion of vitamin D, calcium, vitamin K, phosphorus) would induce increased
      bone turnover while the late stage would be characterized by enhanced bone
      catabolism. Obesity, insulin resistance and hyperleptinemia would be seen during
      the whole course of disease. Healthy female Sprague Dawley rats (n=41) aged 10
      weeks were randomly assigned to sham and treatment groups and sacrificed at 3,
      12, and 14 months after the study began. RESULTS: In the early phase, OVXD was
      associated with an increase in body weight, but not, however, in later stages.
      There was a decrease in bone mineral density and relative bone volume (BV/TV) as
      assessed by Dual Energy X-ray Absorptiometry and micro computed tomography that
      was most severe in the later stages of disease, indicating bone catabolism.
      Osteocalcin limiting bone formation was increased initially, whereas later stages
      (14 months) were characterized by elevated osteopontin, suggesting bone
      remodeling. Severe hyperparathyroidism was present during all stages of disease.
      Only the early phases of disease were characterized by hyperinsulinemia and
      increased adrenocorticotrophic stimulating hormone, whereas in the late stage
      hypoleptinemia rather than hyperleptinemia was seen. CONCLUSION: Markers of bone
      and energy metabolism reflected both an increased bone turn over and ongoing bone
      remodeling associated with initial hyperinsulinemia. Osteopontin and osteocalcin
      can be used to differentiate early and late stages of osteoporosis.

PMID- 25773705
TI  - An aryl-thioether substituted nitrobenzothiadiazole probe for the selective
      detection of cysteine and homocysteine.
AB  - An aryl-thioether substituted nitrobenzothiadiazole probe was synthesized and
      employed to detect cysteine and homocysteine selectively in living cells.
      Interestingly, both cysteine (Cys) and homocysteine (Hcy) promote an enhancement
      of the fluorescence intensity of the probe at pH 7.4 while only Cys gives rise to
      this enhancement under weakly acidic conditions (pH 6.0). 

PMID- 25773706
TI  - NET untangled in TMA?

PMID- 25773707
TI  - Dorsolateral nigral hyperintensity on 3.0T susceptibility-weighted imaging in
      neurodegenerative Parkinsonism.
AB  - BACKGROUND: Absence of a hyperintense, ovoid area within the dorsolateral border
      of the otherwise hypointense pars compacta of the substantia nigra (referred to
      as dorsolateral nigral hyperintensity) on iron-sensitive high-field magnetic
      resonance imaging sequences seems to be a typical finding for patients with
      Parkinson's disease (PD). OBJECTIVE: This study was undertaken to evaluate the
      diagnostic value of the dorsolateral nigral hyperintensity in a cohort of
      patients with neurodegenerative parkinsonism including PD, multiple system
      atrophy (MSA), and progressive supranuclear palsy (PSP) as well as healthy
      controls using high-field susceptibility-weighted imaging (SWI) at 3.0 Tesla (T).
      METHODS: Absence of dorsolateral nigral hyperintensity was assessed on visual
      inspection of anonymized 3.0T SWI scans in a case-control study including 148
      patients with neurodegenerative parkinsonism (PD: n = 104; MSA: n = 22; PSP: n =
      22) and 42 healthy controls. RESULTS: Dorsolateral nigral hyperintensity was
      absent unilaterally in all patients with MSA or PSP, in 83 of 90 patients with
      PD, but only in one of the healthy controls resulting in an overall correct
      classification of 95.2% in discriminating neurodegenerative parkinsonism from
      controls in the per-protocol analysis. Overall correct classification was 93.2%
      in the intent-to-diagnose analysis, including also SWI scans with poor quality
      (12.1% of all scans) for nigral evaluation. CONCLUSION: Visual assessment of
      dorsolateral nigral hyperintensity on high-field SWI scans may serve as a new
      simple diagnostic imaging marker for neurodegenerative parkinsonian disorders.

PMID- 25773708
TI  - Properties of the Energy Bands, Judd-Ofelt Parameters and the Fluorescence of
      Neodymium Chloride (NdCl3) in Methanol, Iso-propanol and Butanol Solvents.
AB  - Absorption bands of neodymium chloride (NdCl3) dissolved in methanol, iso
      propanol and butanol organic solvents at room temperature have been recorded in
      the ultraviolet-visible and near infrared regions between 190 and 1100 nm.
      Adopting a free-ion Hamiltonian we have calculated and assigned the energy
      multiplets of the 4f (3) electronic configuration of the Nd(3+) ion, and thereby
      the best-fit parameters are estimated. We have measured the oscillator strengths
      of the observed absorptions and using the experimentally measured oscillator
      strengths the three Judd-Ofelt intensity parameters Omega2, Omega4 and Omega6
      have been derived. Hence we have calculated the line strengths and the oscillator
      strengths for electric-dipole transitions. An intense fluorescence emission is
      found for (4)F3/2 -> (4)I9/2 transition at 873 nm, upon excitation with 581 nm.
      The fluorescence characteristics are also investigated by evaluating the
      spontaneous transition probability (A), luminescence branching ratio (beta),
      radiative lifetime (tau) and the stimulated emission cross section (sigma). 

PMID- 25773709
TI  - Novel Multicolor Schiff Base Polymers Prepared via Oxidative Polycondensation.
AB  - A series of diimine Schiff bases and their polymers were synthesized via the
      oxidative polycondensation reaction. The structures of the compounds were
      confirmed by (1)H-NMR, (13)C-NMR, FT-IR and UV-vis spectral measurements.
      Electrochemical and optical band gap values of synthesized compounds were
      determined by cyclic voltammetry (CV) and UV-vis measurements, respectively.
      Fluorescence measurements of the compounds were conducted in various solvents.
      The effects of solution concentration on the fluorescence spectra were
      investigated and quantum yield was calculated for the polymer of 5-(diethylamino)
      2-(biphenylmethylene) hydrazonomethylphenol (PDEAHP). According to fluorescence
      measurements, the quantum yield of PDEAHP was found as 16% in DMF solution.
      Thermal characteristics of polymers were studied by TG-DTA and DSC analyses.

PMID- 25773710
TI  - Phenazine Fused Benzo Coumarins with Negative Solvatochromism and Positive
      Solvatochromic Emission--Synthesis, Photo Physical Properties, DFT and TDDFT
      Studies.
AB  - 5-Hydroxybenzo[a]phenazine-6-carbaldehyde was synthesized and condensed with
      substituted active methylene compounds to obtain four novel phenazine fused
      coumarin dyes. Solutions of imidazole containing dyes in various solvents
      exhibited yellow to orange fluorescence while benzothiazole containing dyes
      showed brilliant bluish green fluorescence. The dyes showed pronounced negative
      solvatochromism. However, the emission experienced progressive red shift with
      increasing polarity. The excited states of these dyes are proved to be more polar
      than the ground state. The dyes showed fairly good quantum yield in the range 0.1
      0.7, and displayed high thermal stability, as determined using thermo gravimetric
      analysis. The density functional theory computations showed that intramolecular
      charge transfer occurs from the 3 position to the 7 position. The excited state
      computation using time dependent functional theory predicted the emission well. 

PMID- 25773711
TI  - Screening and Optimization of the Reaction of Polymyxin B Sulphate with NBD-Cl
      for the Synchronous Spectrofluorimetric Determination of Polymyxin B Sulphate in
      Human Plasma.
AB  - An accurate and sensitive synchronous spectrofluorimetric method has been
      developed for the determination of Polymyxin B sulphate (Poly B) in human plasma.
      The method is based on the reaction of non-fluorescent Poly B with 4-chloro-7
      nitrobenzo-2-oxa-1,3-diazole (NBD-Cl) in borate buffer of pH 7 producing a yellow
      color with maximum relative fluorescence at 440 nm using a constant wavelength
      difference Deltalambda = 80 nm. Reaction conditions and other analytical
      parameters were studied and optimized using factorial design. Three level
      factorial designs have been employed for the screening, optimization of all
      experimental variables and determination of their interactions on the final
      product formation. The variables under investigation were: pH of borate buffer,
      volume of buffer, volume of NBD-Cl, temperature, time of heating and volume of
      sulfuric acid. A linear plot between relative fluorescence and concentration was
      obtained over the concentration range 100.00-1200.00 ng mL(-1). The limit of
      detection (LOD) and limit of quantification (LOQ) were found to be 10.31 and
      31.24 ng mL(-1), respectively. The proposed method was validated according to ICH
      guidelines and successfully applied for the determination of Poly B in human
      plasma, where satisfactory results were obtained. The results obtained were
      statistically compared with those of a published method, where no significant
      difference was observed. 

PMID- 25773712
TI  - Lixisenatide reduces postprandial hyperglycaemia via gastrostatic and
      insulinotropic effects.
AB  - BACKGROUND: Lixisenatide is a once-daily, prandial, short-acting glucagon-like
      peptide-1 receptor agonist. Its main antidiabetic effect is to delay gastric
      emptying to control postprandial plasma glucose excursions. The dose-response
      relationship of the integrated insulinotropic and gastrostatic response to
      lixisenatide in healthy volunteers after a standardized liquid meal was
      investigated. METHODS: Twenty healthy subjects received acetaminophen 1000 mg
      with a standardized liquid meal 60 min after a single subcutaneous injection of
      placebo or lixisenatide 2.5, 5, 10 or 20 ug in randomized order separated by a 2-
      to 7-day washout. Acetaminophen pharmacokinetics served as a surrogate to assess
      rate of gastric emptying. Postprandial plasma glucose, insulin, C-peptide and
      glucagon were assessed for 5 h after the meal test, and lixisenatide
      pharmacokinetics were determined for 6 h. RESULTS: After lixisenatide
      administration and prior to the standardized meal, insulin and C-peptide
      transiently increased, while fasting plasma glucose decreased in a dose-dependent
      manner. After the meal, postprandial plasma glucose, insulin and C-peptide were
      dose proportionally reduced with lixisenatide versus placebo for up to 6 h.
      Compared with placebo, glucagon levels were transiently lower after any
      lixisenatide dose, with more sustained reductions after the meal and no apparent
      dose-related trends. Acetaminophen absorption was significantly reduced and
      delayed compared with placebo for lixisenatide doses >=5 ug and demonstrated dose
      dependent slowing of gastric emptying. Lixisenatide displayed near dose
      proportional exposure, with gastrointestinal events increasing with dose.
      CONCLUSIONS: Lixisenatide reduced fasting plasma glucose via stimulation of
      glucose-dependent insulin release and controlled postprandial plasma glucose by
      delaying gastric emptying, demonstrating it to be a valuable option for overall
      glycaemic control.

PMID- 25773713
TI  - Genes from scratch--the evolutionary fate of de novo genes.
AB  - Although considered an extremely unlikely event, many genes emerge from
      previously noncoding genomic regions. This review covers the entire life cycle of
      such de novo genes. Two competing hypotheses about the process of de novo gene
      birth are discussed as well as the high death rate of de novo genes. Despite the
      high death rate, some de novo genes are retained and remain functional, even in
      distantly related species, through their integration into gene networks. Further
      studies combining gene expression with ribosome profiling in multiple populations
      across different species will be instrumental for an improved understanding of
      the evolutionary processes operating on de novo genes. 

PMID- 25773714
TI  - Synthesis and characterization of [(CH3)2NH2][Na0.5Cr0.5(HCOO)3]: a rare example
      of luminescent metal-organic frameworks based on Cr(III) ions.
AB  - A novel formate [(CH3)2NH2][Na0.5Cr0.5(HCOO)3] (DMNaCr) was prepared by a
      solvothermal method. This compound crystallizes in the perovskite-type metal
      formate framework (space group R3[combining macron]) with disordered
      dimethylammonium (DMA(+)) cations. X-ray diffraction, DSC, Raman and IR studies
      show that in contrast to the isostructural iron analogue
      [(CH3)2NH2][Na0.5Fe0.5(HCOO)3] (DMNaFe), DMNaCr does not exhibit any structural
      phase transition at low temperatures. This behavior has been attributed to the
      smaller flexibility of the perovskite-like framework in DMNaCr when compared with
      that of DMNaFe. Dielectric permittivity data reveal pronounced dielectric
      relaxation that is attributed to the dynamical rotation of DMA(+) ions. Electron
      absorption and photoluminescence studies show that this material exhibits
      efficient emission at low temperatures. A detailed analysis of the optical
      properties shows that chromium ions are located at the site of intermediate
      crystal field strength with Dq/B = 2.29. 

PMID- 25773715
TI  - The role of noninvasive positive pressure ventilation in community-acquired
      pneumonia: Which criteria predict success or failure?

PMID- 25773716
TI  - Connectivity patterns and rotamer states of nucleobases determine acid-base
      properties of metalated purine quartets.
AB  - Potentiometric pH titrations and pD dependent (1)H NMR spectroscopy have been
      applied to study the acidification of the exocyclic amino group of adenine (A)
      model nucleobases (N9 position blocked by alkyl groups) when carrying trans
      a2Pt(II) (with a=NH3 or CH3NH2) entities both at N1 and N7 positions. As
      demonstrated, in trinuclear complexes containing central A-Pt-A units, it depends
      on the connectivity pattern of the adenine bases (N7/N7 or N1/N1) and their
      rotamer states (head-head or head-tail), how large the acidifying effect is.
      Specifically, a series of trinuclear complexes with (A-N7)-Pt-(N7-A) and (A-N1)
      Pt-(N1-A) cross-linking patterns and terminal 9-alkylguanine ligands (9MeGH,
      9EtGH) have been analyzed in this respect, and it is shown that, for example, the
      9MeA ligands in trans-,trans-,trans-[Pt(NH3)2(N7-9MeA-N1)2{Pt(NH3)2(9EtGH
      N7)}2](ClO4)6.6H2O (4a) and trans-,trans-,trans-[Pt(NH3)2(N7-9EtA
      N1)2{Pt(CH3NH2)2(9-MeGH-N7)}2](ClO4)6.3H2O (4b) are more acidic, by ca. 1.3 units
      (first pKa), than the linkage isomer trans-,trans-,trans-[Pt(CH3NH2)2(N1-9MeA
      N7)2{Pt(NH3)2(9MeGH-N7)}2](NO3)6.6.25H2O (1b). Overall, acidifications in these
      types of complexes amount to 7-9 units, bringing the pKa values of such adenine
      ligands in the best case close to the physiological pH range. Comparison with pKa
      values of related trinuclear Pt(II) complexes having different co-ligands at the
      Pt ions, confirms this picture and supports our earlier proposal that the close
      proximity of the exocyclic amino groups in a head-head arrangement of (A-N7)-Pt
      (N7-A), and the stabilization of the resulting N6H(-)?H2N6 unit, is key to this
      difference.

PMID- 25773717
TI  - Synthesis and antibacterial activity of novel 4-bromo-1H-indazole derivatives as
      FtsZ inhibitors.
AB  - A series of novel 4-bromo-1H-indazole derivatives as filamentous temperature
      sensitive protein Z (FtsZ) inhibitors were designed, synthesized, and assayed for
      their in vitro antibacterial activity against various phenotypes of Gram-positive
      and Gram-negative bacteria and their cell division inhibitory activity. The
      results indicated that this series showed better antibacterial activity against
      Staphylococcus epidermidis and penicillin-susceptible Streptococcus pyogenes than
      the other tested strains. Among them, compounds 12 and 18 exhibited 256-fold and
      256-fold more potent activity than 3-methoxybenzamide (3-MBA) against penicillin
      resistant Staphylococcus aureus, and compound 18 showed 64-fold better activity
      than 3-MBA but 4-fold weaker activity than ciprofloxacin in the inhibition of S.
      aureus ATCC29213. Particularly, compound 9 presented the best activity (4 ug/mL)
      against S. pyogenes PS, being 32-fold, 32-fold, and 2-fold more active than 3
      MBA, curcumin, and ciprofloxacin, respectively, but it was four times less active
      than oxacillin sodium. In addition, some synthesized compounds displayed moderate
      inhibition of cell division against S. aureus ATCC25923, Escherichia coli
      ATCC25922, and Pseudomonas aeruginosa ATCC27853, sharing a minimum cell division
      concentration of 128 ug/mL.

PMID- 25773718
TI  - Effects of Temperature on Growth, Sporulation, and Competition of Mountain Pine
      Beetle Fungal Symbionts.
AB  - The mountain pine beetle, Dendroctonus ponderosae, depends on two fungi,
      Grosmannia clavigera and Ophiostoma montium, to augment a nutrient-poor woody
      food resource. Because the two fungi exert differential effects on the host
      beetle, temperature-driven differences in fungal growth and competition outcomes
      have a strong potential to influence host population dynamics. Weisolated fungi
      from beetles and wood from three locations in Montana and Utah, USA, and measured
      their growth rates and sporulation between 5 and 35  degrees C on artificial
      media. We also measured growth rates and percent resource capture for each fungus
      at 10, 15, 21, and 25  degrees C during inter- and intra-specific competition. G.
      clavigera excelled at resource capture at most temperatures. Its optimal growth
      temperature occurs around 20  degrees C while that of O. montium occurs near 30 
      degrees C. There was no effect of collection site on growth or sporulation;
      however, O. montium exhibited greater variability in response to temperature than
      did G. clavigera. Sporulation of G. clavigera was greatest at 30  degrees C while
      O. montium sporulated at low levels across all temperatures. During competition
      experiments, G. clavigera captured more resources than O. montium at most
      temperatures and captured a greater percentage of resources at a greater rate
      during inter-specific competition than during intra-specific competition. In
      contrast, O. montium captured a greater percentage of resources during intra
      specific competition. These results demonstrate that temperature can
      differentially affect growth, sporulation, and resource capture of the two
      symbionts, indicating that it may be an important factor influencing the
      composition and dynamics of the symbiosis.

PMID- 25773719
TI  - Nanoformulated Mutant SurR9-C84A: a Possible Key for Alzheimer's and its
      Associated Inflammation.
AB  - PURPOSE: Alzheimer's disease (AD) is one of the untreatable neurodegenerative
      diseases characterised by the pathologic amyloid plaque deposition and
      inflammation. The aim of this study is to evaluate the neuroprotective effects of
      nanoformulated SurR9-C84A, a survivin mutant belonging to the inhibitors of the
      apoptosis (IAP) protein family. The effect of SurR9-C84A was studied against the
      beta-amyloid toxicity and various inflammatory insults in the differentiated SK-N
      SH neurons. METHOD: SurR9-C84A loaded poly(lactic-co-glycolic acid) nanoparticles
      were prepared following the modified double emulsion technique. The
      neuroprotective effect of SurR9-C84A was evaluated against the amyloid-beta
      (Abeta) peptide fragment, N-methyl-D-aspartate (NMDA) toxicity and the
      inflammatory assaults. To mimic the in vivo situation, a co-culture of neurons
      and microglia was also studied to validate these results. RESULTS: SurR9-C84A
      treatments showed improved neuronal health following Abeta, and NMDA toxicity in
      addition to inflammatory insults induced in mono and co-cultures. The
      neuroprotective effect was evident with the reduced neuronal death, accelerated
      expression of neuronal integrity markers (neurofilaments, beta-tubulin III etc.,)
      and the neuroprotective ERK/MAPK signalling. CONCLUSION: The current results
      demonstrated that the SurR9-C84A nanoformulation was very effective in rescuing
      the neurons and holds a potential future application against AD.

PMID- 25773720
TI  - Local Sustained Delivery of 25-Hydroxyvitamin D3 for Production of Antimicrobial
      Peptides.
AB  - PURPOSE: This study seeks to develop fiber membranes for local sustained delivery
      of 25-hydroxyvitamin D3 to induce the expression and secretion of LL-37 at or
      near the surgical site, which provides a novel therapeutic approach to minimize
      the risk of infections. METHODS: 25-hydroxyvitamin D3 loaded poly(L-lactide)
      (PLA) and poly(epsilon-caprolactone) (PCL) fibers were produced by
      electrospinning. The morphology of obtained fibers was characterized using atomic
      force microscope (AFM) and scanning electron microscope (SEM). 25-hydroxyvitamin
      D3 releasing kinetics were quantified by enzyme-linked immunosorbent assay
      (ELISA) kit. The expression of cathelicidin (hCAP 18) and LL-37 was analyzed by
      immunofluorescence staining and ELISA kit. The antibacterial activity test was
      conducted by incubating pseudomonas aeruginosa in a monocytes' lysis solution.
      RESULTS: AFM images suggest that the surface of PCL fibers is smooth, however,
      the surface of PLA fibers is relatively rough, in particular, after encapsulation
      of 25-hydroxyvitamin D3. The duration of 25-hydroxyvitamin D3 release can last
      more than 4 weeks for all the tested samples. Plasma treatment can promote the
      release rate of 25-hydroxyvitamin D3. Human keratinocytes and monocytes express
      significantly higher levels of hCAP18/LL-37 after incubation with plasma treated
      and 25-hydroxyvitamin D3 loaded PCL fibers than the cells incubated with around
      ten times amount of free drug. After incubation with this fiber formulation for 5
      days LL-37 in the lysis solutions of U937 cells can effectively kill the
      bacteria. CONCLUSIONS: Plasma treated and 25-hydroxyvitamin D3 loaded PCL fibers
      induce significantly higher levels of antimicrobial peptide production in human
      keratinocytes and monocytes without producing cytotoxicity.

PMID- 25773722
TI  - Identification of Subvisible Particles in Biopharmaceutical Formulations Using
      Raman Spectroscopy Provides Insight into Polysorbate 20 Degradation Pathway.
AB  - PURPOSE: To study composition and heterogeneity of insoluble subvisible particles
      in Mab formulations resulting from degradation of polysorbate 20 and to develop a
      better understanding of the mechanisms of polysorbate degradation leading to
      particle formation. METHODS: In this study, we exploit the potential of Raman
      microscopy for chemical identification of particles in monoclonal antibody
      formulations. Through a combination of experiments and density functional theory
      (DFT) calculations, we identified unique spectral marker bands for insoluble
      degradation products of polysorbate 20. We first applied our methodology to
      identify particles in model systems containing complex mixtures of fatty acids
      and then to subvisible particles in antibody formulations stored at 5 degrees C
      for several years. RESULTS: Most of the subvisible particles identified were
      comprised of mixtures of fatty acids with no observable signal from fatty acid
      esters consistent with hydrolysis being the predominant degradation mechanism
      leading to particulate formation under these storage conditions. CONCLUSIONS: Our
      methodology is generally applicable for identification of particles in antibody
      formulations and, in particular, has the potential to give detailed information
      about particle heterogeneity and insight into mechanistic aspects of particle
      formation.

PMID- 25773724
TI  - Certified ion implantation fluence by high accuracy RBS.
AB  - From measurements over the last two years we have demonstrated that the charge
      collection system based on Faraday cups can robustly give near-1% absolute
      implantation fluence accuracy for our electrostatically scanned 200 kV Danfysik
      ion implanter, using four-point-probe mapping with a demonstrated accuracy of 2%,
      and accurate Rutherford backscattering spectrometry (RBS) of test implants from
      our quality assurance programme. The RBS is traceable to the certified reference
      material IRMM-ERM-EG001/BAM-L001, and involves convenient calibrations both of
      the electronic gain of the spectrometry system (at about 0.1% accuracy) and of
      the RBS beam energy (at 0.06% accuracy). We demonstrate that accurate RBS is a
      definitive method to determine quantity of material. It is therefore useful for
      certifying high quality reference standards, and is also extensible to other
      kinds of samples such as thin self-supporting films of pure elements. The more
      powerful technique of Total-IBA may inherit the accuracy of RBS. 

PMID- 25773723
TI  - Combined Microdialysis-Tumor Homogenate Method for the Study of the Steady State
      Compartmental Distribution of a Hydrophobic Anticancer Drug in Patient-Derived
      Xenografts.
AB  - PURPOSE: To develop a reproducible microdialysis-tumor homogenate method for the
      study of the intratumor distribution of a highly hydrophobic anticancer drug (SN
      38; 7-ethyl-10-hydroxycamptothecin) in neuroblastoma patient-derived xenografts.
      METHODS: We studied the nonspecific binding of SN-38 to the microdialysis tubing
      in the presence of 2-hydroxypropyl-beta-cyclodextrin (HPBCD) in the perfusate. We
      calibrated the microdialysis probes by the zero flow rate (ZFR) method and
      calculated the enhancement factor (f = extrapolated SN-38 concentration at the
      ZFR / SN-38 concentration in the dialysed solution) of HPBCD. We characterized
      the extravasation of HPBCD to tumors engrafted in mice. In vivo microdialysis and
      terminal homogenate data at the steady state (subcutaneous pump infusions) were
      used to calculate the volume of distribution of unbound SN-38 (Vu,tumor) in
      neuroblastoma. RESULTS: HPBCD (10% w/v) in the perfusate prevented the
      nonspecific binding of SN-38 to the microdialysis probe and enhanced SN-38
      recovery (f = 1.86). The extravasation of HPBCD in the tumor during microdialysis
      was lower than 1%. Vu,tumor values were above 3 mL/g tumor for both neuroblastoma
      models and suggested efficient cellular penetration of SN-38. CONCLUSIONS: The
      method contributes to overcome the limitations of the microdialysis technique in
      hydrophobic drugs and provides a powerful tool to characterize compartmental
      anticancer drug distribution in xenografts.

PMID- 25773725
TI  - Shift work and hypertension: Prevalence and analysis of disease pathways in a
      German car manufacturing company.
AB  - BACKGROUND: Hypertension and cardiovascular disease (CVD) may share a similar
      pathophysiology. Despite shift workers' CVD excess risk, studies on shift work
      and hypertension are inconclusive. METHODS: Blood pressure and shift status for
      25,343 autoworkers were obtained from medical check-ups and company registers.
      Cross-sectional associations modeling the total effect from shift work (day
      shifts, shift work without nights, rotating shift work with nights, and night
      shifts) on hypertension were assessed. By sequential adjustments, the influence
      of behavioral, psychosocial, and physiological factors on the total effect was
      examined, with subsequent mediation and moderation analyses. RESULTS: Adjusted
      for confounders, shift work without nights (vs. day shifts) was significantly
      associated with hypertension (OR 1.15, 95%CI 1.02-1.30). The total effect was
      mediated by BMI, physical inactivity, and sleep disorders. No moderation of the
      total effect by behaviors was found. CONCLUSION: The association between shift
      work and hypertension seems mainly attributable to behavioral mechanisms.

PMID- 25773726
TI  - Enzymatic hydrolysis in an aqueous organic two-phase system using centrifugal
      partition chromatography.
AB  - Multi-phase reaction systems, mostly aqueous organic systems, are used in enzyme
      catalysis to convert hydrophobic substrates which are almost insoluble in aqueous
      media. In this study, a Centrifugal Partition Chromatograph is used as a compact
      device for enzymatic multi-phase reaction that combines efficient substrate
      supply to the aqueous phase and separation of both phases in one apparatus. A
      process design procedure to systematically select the aqueous and organic phase
      to achieve stable and efficient reaction rates and operation conditions in
      Centrifugal Partition Chromatography for efficient mixing and separation of the
      phases is presented. The procedure is applied to the hydrolysis of 4-nitrophenyl
      palmitate with a lipase derived from Candida rugosa. It was found that the
      hydrolysis rate of 4-nitrophenyl palmitate was two times higher in Centrifugal
      Partition Chromatography than in comparable stirred tank reactor experiments. 

PMID- 25773727
TI  - Separation of therapeutic peptides with cyclofructan and glycopeptide based
      columns in hydrophilic interaction liquid chromatography.
AB  - Three cyclofructan-based, two glycopeptide-based, and one zwitterionic column
      used in the HILIC mode were assessed within a graphical framework based on
      different functional characteristics contributing to selectivity. The
      characteristics of these six HILIC columns are put in the perspective of 33
      columns evaluated previously. The isopropyl carbamate modified cyclofructan 6
      (CF6) stationary phase, Larihc P, showed reduced component contributions for
      hydrophilicity and hydrogen bonding relative to the native cyclofructan 6 column
      (Frulic N). Both Frulic N and Larihc P exhibited cation exchange attributed
      primarily to deprotonation of residual unsubstituted silica with the greater
      exchange ascribed to the reduced loading of CF6 observed for Larihc P. The
      cyclofructan 6 column with a polymeric styrene divinylbenzene support (MCI GELTM
      CRS100) showed distinct selectivities consistent with its decreased cation
      exchange attributable to its nonionic core. The Chirobiotic T, Chirobiotic V, and
      ZI-DPPS columns displayed hydrophilicity and ion exchange selectivities similar
      to other zwitterionic stationary phases. All of the more hydrophilic columns
      showed excellent separation for the four classes of therapeutic peptides
      investigated: microbial secondary metabolites used as immune suppressants,
      synthetic gonadotropin hormones, synthetic cyclic disulfide-linked hormone
      regulating hormones, and non-ribosomally derived polycyclic antibiotics.
      Resolution provided by these columns and ZIC-HILIC is compared for each class of
      peptide. Frulic N is primarily suitable for use in the HILIC mode whereas
      Chirobiotic T, because of its increased efficiency and selectivity, can be useful
      in both HILIC and reverse phase modes. In some Chirobiotic T applications,
      addition of low levels of a strong additive (trifluoroacetic acid, formic acid,
      etc.) to the mobile phase can be beneficial. In these peptide analyses, a
      relative weakening of the often-dominant ionic interaction between analyte and
      residual charge on the stationary phase improved resolution and selectivity. 

PMID- 25773728
TI  - Equal care for own versus adopted infant in tufted capuchins (Sapajus spp.).
AB  - This study describes a case of adoption by a female tufted capuchin (Sapajus
      spp.) who spontaneously adopted a newborn immediately after he was abandoned,
      then raised him successfully with her own infant. For 7 weeks, we observed the
      adoptive mother, the adoptee (3 days old at the time of adoption) and the
      biological infant (4 days old) in order to compare the behavior of the female
      towards each infant. We focused our attention on different maternal behavioral
      patterns: grooming, carrying and cuddling behaviors, and we also considered
      suckling and independent locomotion by the infants. Our results showed no
      difference in the active care of the adoptive mother. The only significant
      distinction found between the two infants concerned suckling durations, which
      were seen to be longer for the adoptee than for the biological infant. We
      suggested that this could be linked to the gender of the infants, the male
      adoptee having greater need for milk than the biological daughter.

PMID- 25773729
TI  - Penalized regression for interval-censored times of disease progression:
      Selection of HLA markers in psoriatic arthritis.
AB  - Times of disease progression are interval-censored when progression status is
      only known at a series of assessment times. This situation arises routinely in
      clinical trials and cohort studies when events of interest are only detectable
      upon imaging, based on blood tests, or upon careful clinical examination. We
      consider the problem of selecting important prognostic biomarkers from a large
      set of candidates when disease progression status is only known at irregularly
      spaced and individual-specific assessment times. Penalized regression techniques
      (e.g., LASSO, adaptive LASSO, and SCAD) are adapted to handle interval-censored
      time of disease progression. An expectation-maximization algorithm is described
      which is empirically shown to perform well. Application to the motivating study
      of the development of arthritis mutilans in patients with psoriatic arthritis is
      given and several important human leukocyte antigen (HLA) variables are
      identified for further investigation. 

PMID- 25773730
TI  - Cryoglobulinemic purpura in visceral leishmaniasis.

PMID- 25773731
TI  - Long term survival with the combination of interferon and chemotherapy in
      metastatic melanoma.
AB  - The prognosis of metastatic melanoma is poor. Pre-targeted treatment era, the
      combination of interferon-alpha (IF-alpha) plus chemotherapy had been used and
      have generally short response duration. Herein, we present a metastatic melanoma
      case that achieved long-term durable complete response (CR) IF-alpha plus
      chemotherapy and IF-alpha maintenance therapy and had lower Regulatory T (Treg)
      cells. A fifty-year old woman was admitted to the hospital with metastatic
      melanoma. Lactate dehydrogenase (LDH) level was 660U/L. The percentage of
      CD4+CD25+ Treg cells was 2.4% in CD4+ lymphocytes. The IF-alpha plus chemotherapy
      and IF-alpha maintenance were administered. After six courses of chemotherapy, CR
      was achieved. Vitiligo and hypothyroidism occurred. The patient has remained in
      CR for approximately 7 years until second pleural metastases were detected and
      death. The patient has positive prognostic factors such as induction of
      autoimmunity, small tumor volume, mild elevated LDH level, and lower Treg cell
      percentage. She survived long term with CR after IF-alpha treatment with
      concurrent chemotherapy and maintenance. IF-alpha plus chemotherapy may be a
      treatment option for metastatic melanoma in selected cases who cannot reach new
      targeted drugs.

PMID- 25773733
TI  - Importance of cultural dermatology in India.

PMID- 25773734
TI  - An improved method to demonstrate macrophages in teleosts.
AB  - A method to demonstrate macrophages using an optical microscope is described and
      discussed for various teleostean tissues. The fish specimens were injected
      intraperitoneally with horse ferritin particles, which were then endocytosed by
      macrophages before the sacrifice of the specimen. Ferritin-filled endosomes
      within the macrophages were visualized using acidic ferrohexacyanide to create
      large granules filled with Prussian blue precipitates. This technique makes it
      possible to demonstrate fish macrophages clearly and precisely within a large
      volume of tissue using an optical microscope. 

PMID- 25773732
TI  - The impact of early neglect on defensive and appetitive physiology during the
      pubertal transition: a study of startle and postauricular reflexes.
AB  - This study tested the effect of early neglect on defensive and appetitive
      physiology during puberty. Emotion-modulated reflexes, eye-blink startle
      (defensive) and postauricular (appetitive), were measured in 12-to-13-year-old
      internationally adopted youth (from foster care or from institutional settings)
      and compared to non-adopted US born controls. Startle Reflex: adopted youth
      displayed lower overall startle amplitude across all valences and startle
      potentiation to negative images was negatively related to severity of pre
      adoption neglect. Postauricular reflex (PAR): adopted youth showed larger PAR
      magnitude across all valences. Puberty: adopted youth showed diminished PAR
      potentiation to positive images and startle potentiation during mid/late puberty
      versus the opposite pattern in not-adopted. Early neglect was associated with
      blunted fast defensive reflexes and heightened fast appetitive reflexes. After
      puberty, early neglected youth showed physiological hyporeactivity to threatening
      and appetitive stimuli versus heightened reactivity in not adopted youth.
      Behavioral correlates in this sample and possible neurodevelopmental mechanisms
      of psychophysiological differences are discussed.

PMID- 25773735
TI  - Eucalyptol suppresses matrix metalloproteinase-9 expression through an
      extracellular signal-regulated kinase-dependent nuclear factor-kappa B pathway to
      exert anti-inflammatory effects in an acute lung inflammation model.
AB  - OBJECTIVES: The acute lung injury (ALI) model is characterised by a severe acute
      inflammatory response in the lungs that represents the pathogenesis of acute
      respiratory distress syndrome (ARDS). In this study, we sought to elucidate the
      anti-inflammatory mechanism of eucalyptol in relation to tissue remodelling in
      acute lung inflammation. METHODS: BALB/C mice were intraperitoneally injected
      with eucalyptol (100, 200 or 400 mg/kg) or dexamethasone (1 mg/kg) 1 h before
      intratracheal challenge with lipopolysaccharide (LPS; 1.5 mg/kg) and sacrificed
      after 4 h. The anti-inflammatory effects of eucalyptol were assessed by
      determining cell counts, measuring cytokine and nitric oxide production and
      performing Western blotting and histological analyses. KEY FINDINGS: Eucalyptol
      attenuated inflammation-associated increases in cell numbers, matrix
      metalloproteinase-9 (MMP-9) expression, production of cytokines (tumour necrosis
      factor-alpha and interleukin-6) and nitric oxide, and nuclear factor-kappa B (NF
      kappaB) and phosphorylated extracellular signal-regulated kinase protein levels
      induced by LPS in bronchoalveolar lavage fluid from ALI mice. Furthermore,
      pretreatment with 400 mg/kg eucalyptol prevented LPS-induced histopathological
      changes. Collectively, these results indicate that eucalyptol acts through a
      mechanism involving decreased MMP-9 expression and an extracellular signal
      regulated kinase-dependent NF-kappaB pathway to exert anti-inflammatory actions
      in acute lung inflammation. CONCLUSIONS: Thus, eucalyptol may be a potentially
      important agent in the treatment of pulmonary inflammation.

PMID- 25773737
TI  - Hepatitis E Virus: First Description in a Pet House Rabbit. A New Transmission
      Route for Human?
AB  - In this work, we identified for the first time hepatitis E virus (HEV) in a pet
      house rabbit, an adult 7 years old female of domestic rabbit (Oryctolagus
      cuniculus). Importantly, the resulting phylogenetic tree showed that the HEV
      strain identified in the pet house rabbit was closely related to a human HEV
      sequence; this finding reawakens concerns regarding the zoonotic risk represented
      by HEV in animals and expands to house rabbit the spectrum of potential source of
      infection for humans. Potential for domestic transmission of HEV to humans should
      be taken into account.

PMID- 25773738
TI  - Seizures in setting of dementia.
AB  - OPINION STATEMENT: Dementia, especially Alzheimer's disease, is an important
      cause of seizures and epilepsy midst the elderly. With the increasing life span,
      the incidence of dementia and epilepsy is expected to increase exponentially.
      Care of patients with advanced dementia can be demanding and seizures add to this
      burden. Though recognition of seizures in these patients can be difficult,
      seizures in these patients tend to be highly responsive to pharmacological
      therapy. However, choosing the right antiepileptic drug can be a challenge and
      complicated by altered kinetics and polypharmacy. While ongoing seizures can
      worsen the cognitive status in these patients, antiepileptic drugs could also add
      to the cognitive burden. The newer generation drugs show promise in terms of
      their side effect profile without compromising on the efficacy.

PMID- 25773739
TI  - Falling behind? Understanding implementation science in future emergency
      department management strategies for geriatric fall prevention.

PMID- 25773740
TI  - Lowering LDL cholesterol is good, but how and in whom?

PMID- 25773742
TI  - Olodaterol: a review of its use in chronic obstructive pulmonary disease.
AB  - Olodaterol (Striverdi((r)) Respimat((r))) is an inhaled long-acting beta2
      adrenoceptor agonist (LABA) indicated as a once-daily maintenance bronchodilator
      therapy in adults with COPD. Several well-designed phase III trials have assessed
      use of the drug over 6 or 48 weeks in this patient population. In these studies,
      once-daily olodaterol improved lung function relative to placebo over 48 weeks of
      treatment, with such improvements being achieved and maintained within the 24-h
      dosage interval, supporting its once-daily administration. In addition, combined
      analyses of 48-week trials indicated that olodaterol reduces rescue medication
      use and may also improve dyspnoea and health-related quality of life, and
      crossover studies showed improvements in exercise endurance after 6 weeks of
      treatment with the drug. Pooled analyses of crossover studies assessing 24-h
      bronchodilation after 6 weeks of therapy indicated that once-daily olodaterol has
      a 24-h bronchodilatory profile generally similar to that of once-daily tiotropium
      bromide and twice-daily formoterol. Olodaterol was generally well tolerated and
      had an acceptable cardiovascular and respiratory adverse event profile. However,
      further longer-term and active comparator-controlled studies would be beneficial,
      including trials powered to assess COPD exacerbations.

PMID- 25773743
TI  - Erratum to: abacavir/dolutegravir/lamivudine single-tablet regimen: a review of
      its use in HIV-1 infection.

PMID- 25773741
TI  - Histone H3 mutations--a special role for H3.3 in tumorigenesis?
AB  - Brain tumors are the most common solid tumors in children. Pediatric high-grade
      glioma (HGG) accounts for ~8-12 % of these brain tumors and is a devastating
      disease as 70-90 % of patients die within 2 years of diagnosis. The failure to
      advance therapy for these children over the last 30 years is largely due to
      limited knowledge of the molecular basis for these tumors and a lack of disease
      models. Recently, sequencing of tumor cells revealed that histone H3 is
      frequently mutated in pediatric HGG, with up to 78 % of diffuse intrinsic pontine
      gliomas (DIPGs) carrying K27M and 36 % of non-brainstem gliomas carrying either
      K27M or G34R/V mutations. Although mutations in many chromatin modifiers have
      been identified in cancer, this was the first demonstration that histone
      mutations may be drivers of disease. Subsequent studies have identified high
      frequency mutation of histone H3 to K36M in chondroblastomas and to G34W/L in
      giant cell tumors of bone, which are diseases of adolescents and young adults.
      Interestingly, the G34 mutations, the K36M mutations, and the majority of K27M
      mutations occur in genes encoding the replacement histone H3.3. Here, we review
      the peculiar characteristics of histone H3.3 and use this information as a
      backdrop to highlight current thinking about how the identified mutations may
      contribute to disease development. 

PMID- 25773744
TI  - Angiopoietin-2: a multifaceted cytokine that functions in both angiogenesis and
      inflammation.
AB  - Angiogenesis and inflammation are two highly linked processes. In the last
      decade, several factors with dual function in both of these major pathways have
      been identified. This review focuses on angiopoietin-2 (Ang-2), an important
      proangiogenic factor that has more recently been implicated in mediating
      inflammatory processes as well. Ang-2 is upregulated in multiple inflammatory
      diseases and has been implicated in the direct control of inflammation-related
      signaling pathways. As a consequence of its multiple roles, designs for
      therapeutic targeting of Ang-2 should consider the dual function of this factor
      in regulating angiogenesis and inflammation. 

PMID- 25773746
TI  - Dopamine and Huntington's disease.
AB  - Huntington's disease (HD) is an incurable, inherited, progressive
      neurodegenerative disorder that is defined by a combination of motor, cognitive
      and psychiatric features. Pre-clinical and clinical studies have demonstrated an
      important role for the dopamine (DA) system in HD with dopaminergic dysfunction
      at the level of both DA release and DA receptors. It is, therefore, not
      surprising that the drug treatments most commonly used in HD are anti
      dopaminergic agents. Their use is based primarily on the belief that the
      characteristic motor impairments are a result of overactivation of the central
      dopaminergic pathways. While this is a useful starting place, it is clear that
      the behavior of the central dopaminergic pathways is not fully understood in this
      condition and may change as a function of disease stage. In addition, how
      abnormalities in dopaminergic systems may underlie some of the non-motor features
      of HD has also been poorly investigated and this is especially important given
      the greater burden these place on the patients' and families' quality of life. In
      this review, we discuss what is known about central dopaminergic pathways in HD
      and how this informs us about the mechanisms of action of the dopaminergic
      therapies used to treat it. By doing so, we will highlight some of the paradoxes
      that exist and how solving them may reveal new insights for improved treatment of
      this currently incurable condition, including the possibility that such drugs may
      even have effects on disease progression and pathogenesis. 

PMID- 25773745
TI  - Naringin protects against anoxia/reoxygenation-induced apoptosis in H9c2 cells
      via the Nrf2 signaling pathway.
AB  - Naringin (Nar) is a major and active flavanone glycoside derivative of several
      citrus species. The antioxidant properties of Nar have an important function in
      its cardioprotective effects in various models. However, the effects of Nar on
      Nrf2 activation and the expression of its downstream genes in myocardial cells
      are yet to be elucidated. This study was designed to investigate the protective
      effects of Nar against anoxia/reoxygenation (A/R)-induced injury in H9c2 cells
      and determine its effects on the activity of Nrf2 and the expression of phase II
      antioxidant enzymes. H9c2 cells were pretreated with Nar for 6 h before exposure
      to A/R. A/R treatment severely injured the H9c2 cells, which was accompanied by
      apoptosis. Nar also suppressed the A/R-induced mitochondrial membrane
      depolarization and caspase-3 activation. Nar pretreatment significantly reduced
      the apoptotic rate by enhancing the endogenous anti-oxidative activity of
      superoxide dismutase, glutathione peroxidase, and catalase, thereby inhibiting
      intracellular reactive oxygen species generation. Moreover, the presence of Nar
      alone in H9c2 cells increased the nuclear translocation of Nrf2 in a dose- and
      time-dependent manner, as well as consistently increased the protein levels of
      heme oxygenase (HO-1) and glutamate cysteine ligase (GCLC). Nar increased the
      phosphorylation of ERK1/2, PKCdelta, and AKT. However, the Nar-mediated Nrf2
      activation and cardioprotection were abolished through the genetic silencing of
      Nrf2 by siRNA and partially inhibited by specific inhibitors of ERK1/2, PKCdelta,
      and AKT. Therefore, Nar provided cardioprotection by inducing the phosphorylation
      of ERK1/2, PKCdelta, and AKT, which subsequently activated Nrf2 and its
      downstream genes. 

PMID- 25773747
TI  - Preparation and properties evaluation of biolubricants derived from canola oil
      and canola biodiesel.
AB  - This study demonstrates the evaluation and comparison of the lubricity properties
      of the biolubricants prepared from the feed stocks such as canola oil and canola
      biodiesel. Biolubricant from canola biodiesel has a low cloud and pour point
      properties, better friction and antiwear properties, low phase transition
      temperature, is less viscous, and has the potential to substitute petroleum-based
      automotive lubricants. Biolubricant from canola oil has high thermal stability
      and is more viscous and more effective at higher temperature conditions. This
      study elucidates that both the biolubricants are attractive, renewable, and
      ecofriendly substitutes for the petroleum-based lubricants.

PMID- 25773748
TI  - Fate mapping of ptf1a-expressing cells during pancreatic organogenesis and
      regeneration in zebrafish.
AB  - BACKGROUND: Pancreas development in zebrafish shares many features with mammals,
      including the participation of epithelial progenitor cells expressing pancreas
      transcription factor 1a (ptf1a). However, to date it has remained unclear
      whether, as in mammals, ptf1a-expressing zebrafish pancreatic progenitors are
      able to contribute to multiple exocrine and endocrine lineages. To delineate the
      lineage potential of ptf1a-expressing cells, we generated ptf1a:creER(T2)
      transgenic fish and performed genetic-inducible lineage tracing in developmental,
      regenerating, and ptf1a-deficient zebrafish pancreas. RESULTS: In addition to
      their contribution to the acinar cell lineage, ptf1a-expressing cells give rise
      to both pancreatic Notch-responsive-cells (PNCs) as well as small numbers of
      endocrine cells during pancreatic development. In fish with ptf1a
      haploinsufficiency, a higher proportion of ptf1a lineage-labeled cells are traced
      into the PNC and endocrine compartments. Further reduction of ptf1a gene dosage
      converts pancreatic progenitor cells to gall bladder and other non-pancreatic
      cell fates. CONCLUSIONS: Our results confirm the presence of multipotent ptf1a
      expressing progenitor cells in developing zebrafish pancreas, with reduced ptf1a
      dosage promoting greater contributions towards non-acinar lineages. As in
      mammals, loss of ptf1a results in conversion of nascent pancreatic progenitor
      cells to non-pancreatic cell fates, underscoring the central role of ptf1a in
      foregut tissue specification.

PMID- 25773749
TI  - New Protocol to Optimize iPS Cells for Genome Analysis of Fibrodysplasia
      Ossificans Progressiva.
AB  - Successful in vitro disease-recapitulation using patient-specific induced
      pluripotent stem cells (iPSCs) requires two fundamental technical issues:
      appropriate control cells and robust differentiation protocols. To investigate
      fibrodysplasia ossificans progressiva (FOP), a rare genetic disease leading to
      extraskeletal bone formation through endochondral ossification, gene-corrected
      (rescued) iPSC clones (resFOP-iPSC) were generated from patient-derived iPSC (FOP
      iPSC) as genetically matched controls, and the stepwise induction method of
      mesenchymal stromal cells (iMSCs) through neural crest cell (NCC) lineage was
      used to recapitulate the disease phenotype. FOP-iMSCs possessing enhanced
      chondrogenic ability were transcriptionally distinguishable from resFOP-iMSCs and
      activated the SMAD1/5/8 and SMAD2/3 pathways at steady state. Using this method,
      we identified MMP1 and PAI1 as genes responsible for accelerating the
      chondrogenesis of FOP-iMSCs. These data indicate that iMSCs through NCC lineage
      are useful for investigating the molecular mechanism of FOP and corresponding
      drug discovery.

PMID- 25773750
TI  - Using published data in Mendelian randomization: a blueprint for efficient
      identification of causal risk factors.
AB  - Finding individual-level data for adequately-powered Mendelian randomization
      analyses may be problematic. As publicly-available summarized data on genetic
      associations with disease outcomes from large consortia are becoming more
      abundant, use of published data is an attractive analysis strategy for obtaining
      precise estimates of the causal effects of risk factors on outcomes. We detail
      the necessary steps for conducting Mendelian randomization investigations using
      published data, and present novel statistical methods for combining data on the
      associations of multiple (correlated or uncorrelated) genetic variants with the
      risk factor and outcome into a single causal effect estimate. A two-sample
      analysis strategy may be employed, in which evidence on the gene-risk factor and
      gene-outcome associations are taken from different data sources. These approaches
      allow the efficient identification of risk factors that are suitable targets for
      clinical intervention from published data, although the ability to assess the
      assumptions necessary for causal inference is diminished. Methods and guidance
      are illustrated using the example of the causal effect of serum calcium levels on
      fasting glucose concentrations. The estimated causal effect of a 1 standard
      deviation (0.13 mmol/L) increase in calcium levels on fasting glucose (mM) using
      a single lead variant from the CASR gene region is 0.044 (95 % credible interval 
      0.002, 0.100). In contrast, using our method to account for the correlation
      between variants, the corresponding estimate using 17 genetic variants is 0.022
      (95 % credible interval 0.009, 0.035), a more clearly positive causal effect.

PMID- 25773751
TI  - Low mortality in the poorest areas of Spain: adults residing in provinces with
      lower per capita income have the lowest mortality.
AB  - The objective of this study is to ascertain whether income inequality and per
      capita income of area of residence show a relationship with mortality in Spain.
      Data are from a nation-wide prospective study with a 7-year mortality follow-up
      covering all persons living in Spain's 50 provinces in 2001. In total 28,944,854
      subjects aged 25 years or over at baseline were studied. Rate ratio for total
      mortality and cause-specific mortality, according to provincial income inequality
      and per capita income in two age groups, 25-64 years (adult population) and 65
      years and over (elderly population). Provincial income inequality was not related
      to total mortality or cause-specific mortality. Total mortality rate ratios among
      residents of the poorest versus the richest provinces were 0.89 (95% CI 0.95
      0.93) in men and 0.91 (0.87-0.96) in women, among the adult population; and 1.02
      (0.97-1.08) in men and 1.08 (1.02-1.16) in women, among the elderly population.
      With the exception of cardiovascular-disease mortality for which no association
      with per capita income was observed, adult residents of the poorest provinces
      registered the lowest mortality rate ratio for other causes of death. Elderly
      residents of the poorest provinces registered the highest mortality rate ratio
      for cardiovascular disease and the lowest mortality rate ratio for cancer and
      external causes. Aside from cardiovascular-disease mortality, the lowest
      mortality for most causes of death was registered by residents of the poorest
      provinces. Nevertheless, these findings need to be confirmed by similar studies
      using smaller areas as the unit of analysis.

PMID- 25773753
TI  - On the criteria used for assessing the risk of bias in randomized trials included
      in systematic reviews and meta-analyses addressing adverse effects.

PMID- 25773752
TI  - Physical activity and risk of pancreatic cancer: a systematic review and meta
      analysis.
AB  - Physical activity may prevent pancreatic cancer by regulating body weight and
      decreasing insulin resistance, DNA damage, and chronic inflammation. Previous
      meta-analyses found inconsistent evidence for a protective effect of physical
      activity on pancreatic cancer but those studies did not investigate whether the
      association between physical activity and pancreatic cancer varies by smoking
      status, body mass index (BMI), or level of consistency of physical activity over
      time. To address these issues, we conducted an updated meta-analysis following
      the PRISMA guidelines among 30 distinct studies with a total of 10,501 pancreatic
      cancer cases. Random effects meta-analysis of cohort studies revealed a weak,
      statistically significant reduction in pancreatic cancer risk for high versus low
      levels of physical activity (relative risk (RR) 0.93, 95 % confidence interval
      (CI) 0.88-0.98). By comparison, case-control studies yielded a stronger,
      statistically significant risk reduction (RR 0.78, 95 % CI 0.66-0.94; p
      difference by study design = 0.07). When focusing on cohort studies, physical
      activity summary risk estimates appeared to be more pronounced for consistent
      physical activity over time (RR 0.86, 95 % CI 0.76-0.97) than for recent past
      physical activity (RR 0.95, 95 % CI 0.90-1.01) or distant past physical activity
      (RR 0.95, 95 % CI 0.79-1.15, p-difference by timing in life of physical activity
      = 0.36). Physical activity summary risk estimates did not differ by smoking
      status or BMI. In conclusion, physical activity is not strongly associated with
      pancreatic cancer risk, and the relation is not modified by smoking status or BMI
      level. While overall findings were weak, we did find some suggestion of potential
      pancreatic cancer risk reduction with consistent physical activity over time.

PMID- 25773754
TI  - In memoriam Dimitrios Trichopoulos: an argonaut in search of the golden fleece of
      medicine (1938-2014).
AB  - On December 1, 2014, the epidemiology community bade farewell to one of its most
      distinguished members. Dimitrios Trichopoulos passed away leaving several
      colleagues and students in both sides of the Atlantic and all over the world
      saddened by the loss of a great scientist, mentor and friend. Dimitrios
      Trichopoulos was Professor of Cancer Prevention and Professor of Epidemiology at
      the Harvard School of Public Health, Member of the Athens Academy and President
      of the Hellenic Health Foundation in Greece. He had served as director of the
      Harvard Center for Cancer Prevention; chairman of the Epidemiology Departments at
      the University of Athens and at Harvard; and adjunct professor of medical
      epidemiology at the Karolinska Institute in Sweden. He had published the first
      study linking passive smoking to lung cancer, had done early work on the
      association of hepatitis B and C infections and tobacco smoking with
      hepatocellular carcinoma, and conducted key studies on the role of intrauterine
      exposures in breast cancer etiology. He received several awards and distinctions,
      including honorary Doctorates, the Brinker International Award for Breast Cancer
      Clinical Research, the Julius Richmond Award for the documentation of the role of
      involuntary smoking in the etiology of lung cancer, and the Medal of Honor of the
      International Agency for Research on Cancer for his contributions in cancer
      epidemiology and etiology. He was the teacher and mentor of legions of
      epidemiologists, medical doctors and other health scientists across the world. 

PMID- 25773755
TI  - Dietary glycemic load and risk of cognitive impairment in women: findings from
      the EPIC-Naples cohort.
AB  - Cognitive impairment is a common cause of morbidity in the elderly. The
      relationship between dietary habits and cognitive impairment in a female
      population living in the metropolitan area of Naples, in the Mediterranean part
      of Italy, has been evaluated in the Naples EPIC prospective cohort study. The
      study cohort, enrolled between 1993 and 1997, is composed of 5062 women aged 30
      69 years. At time of enrolment anthropometric measures were performed and
      information about socio-demographic details, clinical data, lifestyle and dietary
      habits were collected. During 2008 and 2009, women 65 years of age or older
      received a telephone interview to evaluate cognitive status (TICS); the derived
      score was used as proxy of cognitive impairment. Analyses were carried out on
      1514 participants. Linear regression model showed negative association between
      TICS score and, respectively, age at baseline (beta = -.31, 95% CI -.34, -.24),
      body mass index (BMI) (beta = -.08, 95% CI -.16, -.01), and glycemic load (GL)
      (beta = -.02, 95% CI -.03, -.01), whereas education level (beta = 0.62, 95% CI
      .56, .69) showed positive association. A logistic regression model, used to
      evaluate determinants of the low cognitive score (TICS score <= 15, 1st tertile),
      confirmed association for previous variables [age (OR 1.1, 95% CI 1.08, 1.15);
      BMI (OR 1.03, 95% CI 1.001, 1.07); GL (OR 1.005, 95% CI 1.001, 1.011); education
      level (OR .82, 95% CI .79, .84)] with, in addition, type II diabetes (OR 1.85,
      95% CI 1.014, 3.4). This study indicates that GL may play a role in determining
      risk of cognitive impairment, besides age, BMI, education and diabetes.

PMID- 25773756
TI  - Hope for non-responders with hepatitis C virus and cirrhosis.

PMID- 25773758
TI  - Involvement of cysteine-rich protein 61 in the epidermal growth factor-induced
      migration of human anaplastic thyroid cancer cells.
AB  - Anaplastic thyroid cancer (ATC) is among the most aggressive types of malignant
      cancer. Epidermal growth factor (EGF) plays a crucial role in the pathogenesis of
      ATC, and patients with thyroid carcinoma typically exhibit increased cysteine
      rich protein 61 (Cyr61). In this study, we found that EGF treatment induced cell
      migration, stress fiber formation, Cyr61 mRNA and protein expressions, and Cyr61
      protein secretion in ATC cells. The recombinant Cyr61 protein significantly
      induced cell migration; however, inhibition of Cyr61 activity by a Cyr61-specific
      antibody abrogated EGF-induced cell migration. EGF treatment also affected
      epithelial-to-mesenchymal transition (EMT)-related marker protein expression, as
      evidenced by an increase in vimentin and a decrease in E-cadherin expression.
      Inhibition of Cyr61 expression by Cyr61 siRNA decreased cell migration and
      reversed the EMT-related marker protein expression. EGF treatment increased the
      phosphorylation of the extracellular signal-regulated kinase (ERK) and cAMP
      response element-binding protein (CREB), and finally activated Cyr61 promoter
      plasmid activity. Our results suggest that Cyr61 is induced by EGF through the
      ERK/CREB signal pathway and that it plays a crucial role in the migration and
      invasion of ATC cells; moreover, Cyr61 might be a therapeutic target for
      metastatic ATC.

PMID- 25773757
TI  - Ledipasvir-sofosbuvir with or without ribavirin to treat patients with HCV
      genotype 1 infection and cirrhosis non-responsive to previous protease-inhibitor
      therapy: a randomised, double-blind, phase 2 trial (SIRIUS).
AB  - BACKGROUND: Patients with cirrhosis resulting from chronic hepatitis C virus
      (HCV) infection are at risk of life-threatening complications, but consistently
      achieve lower sustained virological response (SVR) than patients without
      cirrhosis, especially if treatment has previously failed. We assessed the
      efficacy and safety of the NS5A inhibitor ledipasvir and the nucleotide
      polymerase inhibitor sofosbuvir, with and without ribavirin. METHODS: In this
      multicentre, double-blind trial, between Oct 21, 2013, and Oct 30, 2014, we
      enrolled patients with HCV genotype 1 and compensated cirrhosis who had not
      achieved SVR after successive treatments with pegylated interferon and protease
      inhibitor regimens at 20 sites in France. With a computer-generated randomisation
      sequence, patients were assigned in a 1:1 ratio to receive placebo matched in
      appearance to study drugs for 12 weeks followed by once daily combination fixed
      dose tablets of 90 mg ledipasvir and 400 mg sofosbuvir plus weight-based
      ribavirin for 12 weeks, or ledipasvir-sofosbuvir plus placebo once daily for 24
      weeks. The primary endpoint was SVR 12 weeks after the end of treatment (SVR12),
      for which 95% CIs were calculated with the Clopper-Pearson method. This study is
      registered with ClinicalTrials.gov, number NCT01965535. FINDINGS: Of 172 patients
      screened, 155 entered randomisation, 77 were assigned to receive ledipasvir
      sofosbuvir plus ribavirin and 78 ledipasvir-sofosbuvir. 114 (74%) were men, 151
      (97%), were white, 98 (63%) had HCV genotype 1a, and 145 (94%) had non-CC IL28B
      alleles. SVR12 rates were 96% (95% CI 89-99) for patients in the ledipasvir
      sofosbuvir plus ribavirin group and 97% (91-100) in the ledipasvir-sofosbuvir
      group. One patient discontinued treatment because of adverse events while
      receiving only placebo. The most frequent adverse events were asthenia and
      headache, pruritus, and fatigue. INTERPRETATION: Ledipasvir-sofosbuvir plus
      ribavirin for 12 weeks and ledipasvir-sofosbuvir for 24 weeks provided similarly
      high SVR12 rates in previous non-responders with HCV genotype 1 and compensated
      cirrhosis. The shorter regimen, when given with ribavirin, might, therefore, be
      useful to treat treatment-experienced patients with cirrhosis if longer-term
      treatment is not possible. FUNDING: Gilead Sciences.

PMID- 25773759
TI  - Oversewing staple lines to prevent anastomotic complications in primary ileocolic
      resections for Crohn's disease.
AB  - BACKGROUND: Oversewing staple lines may be a novel way to reduce anastomotic
      complications after primary ileocolic resections for Crohn's disease (CD). STUDY
      DESIGN: This is a single-institution, non-concurrent cohort study of CD patients
      undergoing primary ileocolic resections (ICR) with stapled anastomoses from 2007
      to 2013. Demographic and clinical characteristics were collected. Propensity
      scores were calculated for oversewing versus not. Postoperative outcomes within
      30 days of surgery were collected. Anastomotic leak, intra-abdominal abscess,
      small bowel obstruction, and anastomotic bleed were considered major anastomotic
      complications (MACs). Multivariate analysis controlling for inverse probability
      weights was used to identify predictors of MACs. RESULTS: A total of 269 patients
      were included, of which 120 had undergone oversewing (OS). After controlling for
      propensity scores, not oversewing (NOS) and OS groups were similar in all
      preoperative characteristics with the exception of more laparoscopic resections
      and intracorporeal anastomoses in the NOS group. On univariate analysis, OS was
      protective against MACs (odds ratio (OR) 0.29, p < 0.01). In a multivariable
      model using inverse propensity weights and controlling for laparoscopic and
      intracorporeal approaches, oversewing remained a significant predictor of reduced
      MACs (OR 0.37, p < 0.001), while intracorporeal anastomoses increased their
      likelihood (OR 3.7, p < 0.001). CONCLUSIONS: After controlling for clinical and
      surgical factors, oversewing staple lines in primary ICRs for CD is correlated
      with reduced MACs.

PMID- 25773760
TI  - Effects of blockade of endogenous Gi signaling in Tie2-expressing cells on bone
      formation in a mouse model of heterotopic ossification.
AB  - Available evidence indicates that some Tie2-expressing (Tie2(+) ) cells serve as
      multipotent progenitors that have robust BMP-dependent osteogenic activity and
      mediate heterotopic ossification (HO). Since signaling through the G protein Gi
      is required for cell motility, we hypothesized that blockade of endogenous Gi
      signaling in Tie2(+) cell populations would prevent HO formation. Blockade of Gi
      signaling in Tie2(+) cells was accomplished in transgenic mice with expression of
      pertussis toxin (PTX) under the control of the Tie2 promoter (Tie2(+) /PTX(+) ).
      Bone formation within HOs was evaluated 2 weeks after BMP injection. Expression
      of PTX in Tie2(+) cells significantly reduced the bone volume (BV) of HOs in male
      and female mice. Orthotopic bones were assessed at the distal femur and
      expression of PTX significantly increased trabecular bone fractional volume and
      bone formation rate in females only. In adult Tie2(+) /GFP(+) mice, GFP(+) cells
      appeared both inside and at the surfaces of bone tissue within HOs and in
      orthotopic bones. In summary, blockade of Gi signaling in Tie2(+) cells reduced
      the accrual of HOs and stimulated osteogenesis in orthotopic bones. Targeting of
      Gi protein coupled receptors in Tie2(+) cells may be a novel therapeutic strategy
      in states of abnormal bone formation such as osteoporosis and HO.

PMID- 25773762
TI  - A preliminary study of side population cells in human gastric cancer cell line
      HGC-27.
AB  - BACKGROUND: Cancer stem cell-like side population (SP) cells, which may be
      responsible for recurrence, tumor metastasis, and resistance to cancer therapy,
      have been identified and characterized in several types of cell lines from
      gastric cancer. However, there is no report on isolation of SP cells from human
      gastric cancer cell line HGC-27. This study aims to analyze the proportion of SP
      cells in HGC-27 cell line, differentiate SP from non-side population (NSP) cells,
      and determine whether the SP cells have certain biological properties of stem
      cells. MATERIAL AND METHODS: (1) HGC-27 suspension was prepared and stained with
      Hoechst33342 and PI for flow cytometric isolation of SP (2). Differences in
      proliferation and stemness-related gene expression profiles (CD133, CD44, OCT-4,
      MDR1, EpCAM, and ABCG2) between SP and NSP cells were detected by gastric
      formation assay and quantitative real-time PCR (3). Oncogenicity of SP and NSP
      cells was determined in nude mice in vivo. RESULTS: (1) SP cells accounted for
      0.1-1.0% of HGC-27 cells, and decreased to 0% after verapamil inhibition. Using
      flow cytometry, we sorted 7.5*105 SP cells and most HGC-27 cells were NSP cells
      (2). Gastric formation assay and MTT demonstrated that there was a significant
      difference in proliferation between SP and NSP cells. Gene expression analysis
      showed that the expression of genes was significantly higher in SP cells (3). The
      oncogenicity experiment in nude mice revealed that 105 SP cells were able to form
      tumors, which demonstrated higher tumorigenicity than non-SP cells. CONCLUSIONS:
      These results collectively suggested that SP cells from HGC-27 cell line have
      some cancer stem cell properties and could be used for studying the pathogenesis
      of gastric cancer, which may contribute to discovery of novel therapeutic
      targets.

PMID- 25773761
TI  - The advance of tomato disease-related microRNAs.
AB  - Tomato is a model plant for studying plant-pathogen interactions. As regulatory
      factors, microRNAs (miRNAs) have been widely identified and play crucial roles in
      tomato-pathogen interactions, including host defense and pathogen counter
      defense. Here, the review summarizes the discoveries and highlights of miRNAs in
      tomato diseases. Roles of artificial miRNAs in disease resistance are further
      discussed. Hence, a better understanding of the contribution of miRNAs in tomato
      disease will shed light on strategies in enhancing tomato-pathogen resistance. 

PMID- 25773763
TI  - Pharmacokinetics, safety, and tolerability of rotigotine transdermal system in
      healthy Japanese and Caucasian subjects following multiple-dose administration.
AB  - Rotigotine is a dopamine receptor agonist indicated for the treatment of
      Parkinson's disease and moderate-to-severe restless legs syndrome. Continuous
      transdermal delivery of rotigotine via a silicon-based patch maintains stable
      plasma concentrations over 24 h. The objective of the study was to evaluate the
      pharmacokinetics, safety, and tolerability of a multiple-dose schedule of
      rotigotine transdermal patch in Japanese and Caucasian subjects. In this open
      label, repeated-dose, parallel-group study (ClinicalTrials.gov: NCT01854216),
      healthy male and female subjects of Japanese or Caucasian ethnic origin were
      matched by gender, body mass index, and age. Subjects underwent a 9-day patch
      application period. 12 Japanese and 12 Caucasian subjects were included in the
      pharmacokinetic analyses. Mean apparent doses (actual amount of drug delivered)
      increased proportionally with rotigotine nominal dosages (1, 2, and 4 mg/24 h)
      and were similar for both ethnic groups, with large inter-individual variability.
      Mean plasma concentration-time profiles for unconjugated rotigotine were similar
      in both ethnic groups at day 3 for each dosage. Peak concentrations (C max,ss)
      and area under the concentration-time curves from pre-dose to the concentration
      measured 24 h after administration of patch (AUC(0-24,ss)) showed similar
      exposure in both groups; higher values in Japanese subjects were explained by
      differences in body weight. For total rotigotine, C max,ss and AUC(0-24,ss)
      values were higher in Caucasian subjects and could be explained by small
      differences in apparent dose. Rotigotine was generally well tolerated following
      multiple applications up to 4 mg/24 h. These findings suggest similar dosage
      requirements for rotigotine transdermal system in Japanese and Caucasian
      populations. 

PMID- 25773764
TI  - Adverse pregnancy outcome in patients with low pregnancy-associated plasma
      protein-A: The Indian Experience.
AB  - AIM: The aim of our study was to examine the association of low pregnancy
      associated plasma protein-A (PAPP-A) with adverse pregnancy outcome. MATERIAL AND
      METHODS: A total of 1640 consecutive pregnant women between 9(+5) and 13(+6)
      weeks of pregnancy were recruited. One hundred and thirty women with PAPP-A
      levels < 0.4 multiple of median were followed till delivery and the outcome
      information was obtained for fetal loss, birthweight, growth restriction, preterm
      birth, reduced liquor and development of pre-eclampsia. RESULTS: During the study
      period, 130 (7.92%) women had low PAPP-A and were considered as cases and 200
      women with normal PAPP-A were controls. Intrauterine growth restriction was
      observed in 28 (21.54%) cases as compared to 10 (5%) controls. Pre-eclampsia
      presented in 24 (18.46%) cases and in 18 (9%) controls. Twenty (15.38%) cases had
      preterm delivery compared to 12 (6%) controls. Fifty-six (43.08%) cases delivered
      low-birthweight babies compared to 22 (11%) controls. Thus, the incidence of
      intrauterine growth restriction, preterm birth and low birthweight was
      significantly more in the cases as compared to the control group. CONCLUSIONS:
      PAPP-A is a valuable analyte for predicting risk of adverse pregnancy outcome and
      women with low serum PAPP-A levels would benefit from closer surveillance.

PMID- 25773765
TI  - Application of radiofrequency ablation procedure on a morbidly obese patient with
      a venous ulcer and large saphenous vein.
AB  - Venous ulcers that occur due to chronic venous insufficiency are seen on the
      upper medial malleol of the ankle. Treatment of venous ulcers is protracted and
      generally the success rate is low. Co-morbid factors play an important role in
      the success of treatment of venous ulcers. In this case report, we demonstrate
      successful venous ulcer treatment in a morbidly obese patient with co-morbid
      conditions. 

PMID- 25773767
TI  - William A. Stini (1930-2014).

PMID- 25773766
TI  - Phylogenetic analysis of human metapneumovirus detected in hospitalized patients
      in Kuwait during the years 2009-2011.
AB  - BACKGROUND: Human metapneumovirus (hMPV) is an important cause of both upper and
      lower respiratory tract infections (RTIs) in all age groups. Children, elderly,
      and immunocompromised individuals are the most affected groups. HMPV infection
      accounts for 5% of hospitalized patients with respiratory tract infections in
      Kuwait. It is mostly detected among infants and elderly age groups, and both hMPV
      genotypes A and B circulate in Kuwait. METHODS: In this study, the genetic
      diversity of detected hMPV was evaluated, and a phylogenetic analysis based on
      partial nucleotide and amino acid sequences of the G gene was performed for hMPV
      detected among hospitalized patients with RTIs. RESULTS: Our results showed that
      62% of hMPV sequences belonged to the A genotype and 38% to the B genotype. A2b
      and B2 subtypes were detected and circulated during the study period, whereas A1
      and B1 subtypes were not detected. Based on nucleotide sequences of the G gene,
      most of hMPV strains (57%) were clustered with Indian strains, followed by Greek
      strains (24%) and Canadian strains (14%). One strain (5%) clustered within the B
      genotype but had different branches than B1 and B2 branches. CONCLUSION: Our data
      showed the co-circulation of hMPV genotypes A2b and B2 in Kuwait with genetic
      diversity suggestive of evolution through negative selection.

PMID- 25773770
TI  - Association between HLA-IIgene polymorphism and Helicobacter pylori infection in
      Asian and European population: A meta-analysis.
AB  - BACKGROUND: It is generally considered that HLA-II genes contribute to the
      Helicobacter pylori (Hp) infection and disease development process. AIMS: To
      perform a meta-analysis to explore the relationship between HLA-IIgene
      polymorphism and host susceptibility to Hp infection. METHODS: Relevant cohort
      studies, case-control studies and cross-sectional studies were identified by
      searching Cochrane Library, PubMed, EMBASE, Web of Science and CBM up to July
      2014. The data were extracted and methodological quality of the studies were
      evaluated. RevMan5.0 software was used to perform statistical analysis. RESULTS:
      In Asian population, HLA-DQB1*0303 acted as the protective gene in Hp infection
      (statistically significant pooled OR = 0.54) and the susceptible genes in Hp
      infection involved HLA-DQB1*0401, HLA-DQA1*0103 and HLA-DQA1*0301 (statistically
      significant pooled OR and 95%CI were 3.34(1.93,5.77), 1.64(1.16,2.33) and
      2.03(1.20,3.44) respectively). No statistically significant difference between
      DQB1*0303, HLA-DQA1*0103 and DQA1*0301 and Hp infection in European population
      (P>0.05). And no statistically significant difference (P>0.05) in the overall
      effect of the association between the rest of HLA-IIalleles and Hp infection.
      CONCLUSIONS: In Asian population, the protective gene HLA-DQB1*0303 and the
      susceptible genes HLA-DQB1*0401, HLA-DQA1*0103 and HLA-DQA1*0301 in Hp infection
      were established by meta-analysis. And there was no HLA-IIallele was found to
      associate with Hp infection among European population.

PMID- 25773771
TI  - The biological functions of IL-17 in different clinical expressions of
      Helicobacter pylori-infection.
AB  - Helicobacter pylori (H. pylori) infection is regarded as the major cause of
      various gastric diseases (gastritis, peptic ulcers and gastric cancer) and
      induces the production of several cytokines. Interleukin-17 (IL-17) is recently
      recognized as an important player in the pathophysiology of infectious and immune
      mediated gastrointestinal diseases. H. pylori infection increases IL-17 in the
      gastric mucosa of humans. IL-17 usually causes secretion of IL-8 through
      activation of ERK 1/2 MAP kinase pathway. The released IL-8 attracts neutrophils
      promoting inflammation. T regulatory cells (Tregs) suppress the inflammatory
      reaction driven by IL-17, there by favoring bacterial persistence in H. pylori
      infection. The pathogenesis of H. pylori-induced inflammation is not well
      understood. Inflammation is promoted by both host factors and H. pylori factors,
      such as the proteins cytotoxin associated gene A (cagA) and vacuolating cytotoxin
      A (vacA). IL-1beta, IL-6, tumor necrosis factor (TNF)-alpha, TGF-beta1, IL-17, IL
      18, IL-21 and IL-22 have been reported to be involved in H. pylori-induced
      gastric mucosal inflammation, but the details and relation to different patterns
      of inflammation remain unclear. Numerous studies have demonstrated important
      functions of IL-17 in acute and chronic inflammatory processes. This paper
      reviews the role of IL-17 in gastritis, peptic ulcers and gastric cancer related
      to H. pylori. 

PMID- 25773772
TI  - Outer membrane vesicles isolated from two clinical Acinetobacter baumannii
      strains exhibit different toxicity and proteome characteristics.
AB  - Outer membrane vesicles (OMVs) are well-characterized virulence factors produced
      by Gram-negative bacteria. Here, we isolated two clinical Acinetobacter baumannii
      strains, the multidrug-resistant A. baumannii (MDRAb) A38 and non-MDRAb 5806.
      Strain A38 produced more abundant OMVs than strain 5806 when cultured to the
      early stationary phase. The results from cell proliferation assays and real-time
      PCR analyses indicated that A38 OMVs induced more powerful cytotoxicity and
      stronger innate immune responses compared with 5806 OMVs. Moreover, SDS-PAGE and
      LC-MS/MS analyses revealed that A38 OMVs contained more virulence factors,
      including Omp38, EpsA, Ptk, GroEL, hemagglutinin-like protein, and FilF. Taken
      together, the results of the present study suggest that MDRAb might produce
      abundant OMVs with more virulent factors facilitating the worse outcome, a
      finding that merits further study. 

PMID- 25773773
TI  - Intestinal and hepatic drug transporters: pharmacokinetic, pathophysiological,
      and pharmacogenetic roles.
AB  - The efficacy and safety of pharmacotherapies are determined by the complex
      processes involved in the interactions between drugs with the human body,
      including pharmacokinetic aspects. Among pharmacokinetic factors, it has been
      recognized that drug transporters play critical roles for absorption,
      distribution and excretion of drugs, regulating the membrane transport of drugs.
      The vast amounts of information on drug transporters collected in the past 20
      years have been organized according to biochemical, molecular, genetic, and
      clinical analyses. Novel technologies, public databases, and regulatory
      guidelines have advanced the use of such information in drug development and
      clinical practice. In this review, we selected some clinically important drug
      transporters expressed in the intestine and liver, and introduced the research
      history and current knowledge of their pharmacokinetic, pathophysiological, and
      pharmacogenetic implications.

PMID- 25773775
TI  - Dietary magnesium deficiency affects gut microbiota and anxiety-like behaviour in
      C57BL/6N mice.
AB  - OBJECTIVE: Magnesium deficiency has been associated with anxiety in humans, and
      rodent studies have demonstrated the gut microbiota to impact behaviour. METHODS:
      We investigated the impact of 6 weeks of dietary magnesium deficiency on gut
      microbiota composition and anxiety-like behaviour and whether there was a link
      between the two. A total of 20 C57BL/6 mice, fed either a standard diet or a
      magnesium-deficient diet for 6 weeks, were tested using the light-dark box
      anxiety test. Gut microbiota composition was analysed by denaturation gradient
      gel electrophoresis. RESULTS: We demonstrated that the gut microbiota composition
      correlated significantly with the behaviour of dietary unchallenged mice. A
      magnesium-deficient diet altered the gut microbiota, and was associated with
      altered anxiety-like behaviour, measured by decreased latency to enter the light
      box. CONCLUSION: Magnesium deficiency altered behavior. The duration of magnesium
      deficiency is suggested to influence behaviour in the evaluated test.

PMID- 25773774
TI  - Clinicopathological characteristics and diagnostic performance of Wisteria
      floribunda agglutinin positive Mac-2-binding protein as a preoperative serum
      marker of liver fibrosis in hepatocellular carcinoma.
AB  - BACKGROUND: Wisteria floribunda agglutinin positive Mac-2-binding protein (WFA(+)
      M2BP) is a novel serum marker of liver fibrosis identified in glycoproteomic
      biomarker screening studies, and its clinicopathological characteristics have yet
      to be elucidated sufficiently for clinical utilization. METHODS: We
      retrospectively analyzed the clinicopathology data and serum WFA(+)-M2BP levels
      in 376 hepatocellular carcinoma patients undergoing liver surgery. WFA(+)-M2BP
      was quantified in frozen serum samples collected at the time of surgery using the
      FastLec-Hepa method. RESULTS: Significant independent determinants of serum
      WFA(+)-M2BP levels included pathological diagnosis of cirrhosis, female gender,
      hepatitis C virus (HCV) infection, and liver dysfunction characteristics, such as
      abnormal indocyanine green retention rate at 15 min, platelet counts, albumin
      levels, alanine aminotransferase levels, and total bilirubin levels. Serum WFA(+)
      M2BP levels increased with the pathological fibrosis stage and liver dysfunction
      severity. HCV infection significantly affected serum WFA(+)-M2BP levels
      throughout the pathological and functional progression of liver fibrosis, and the
      effect of gender was significant only in F4 stage patients with severe liver
      dysfunction. The diagnostic thresholds for cutoff index values for cirrhosis were
      1.435 and 4.615 in HCV-negative and HCV-positive patients, respectively. Serum
      WFA(+)-M2BP levels at the time of operation were a significant predictor of
      hepatocellular carcinoma recurrence and overall survival in both HCV-negative and
      HCV-positive patients. CONCLUSIONS: Serum WFA(+)-M2BP levels reflected both the
      pathological and functional progression of liver fibrosis comprehensively and
      continuously. Elevated WFA(+)-M2BP levels were a significant risk factor for
      tumor recurrence and decreased overall survival after liver surgery independent
      of HCV infection.

PMID- 25773777
TI  - Zinc promotes proliferation and activation of myogenic cells via the PI3K/Akt and
      ERK signaling cascade.
AB  - Skeletal muscle stem cells named muscle satellite cells are normally quiescent
      but are activated in response to various stimuli, such as injury and overload.
      Activated satellite cells enter the cell cycle and proliferate to produce a large
      number of myogenic progenitor cells, and these cells then differentiate and fuse
      to form myofibers. Zinc is one of the essential elements in the human body, and
      has multiple roles, including cell growth and DNA synthesis. However, the role of
      zinc in myogenic cells is not well understood, and is the focus of this study. We
      first examined the effects of zinc on differentiation of murine C2C12 myoblasts
      and found that zinc promoted proliferation, with an increased number of cells
      incorporating EdU, but inhibited differentiation with reduced myogenin expression
      and myotube formation. Furthermore, we used the C2C12 reserve cell model of
      myogenic quiescence to investigate the role of zinc on activation of myogenic
      cells. The number of reserve cells incorporating BrdU was increased by zinc in a
      dose dependent manner, with the number dramatically further increased using a
      combination of zinc and insulin. Akt and extracellular signal-regulated kinase
      (ERK) are downstream of insulin signaling, and both were phosphorylated after
      zinc treatment. The zinc/insulin combination-induced activation involved the
      phosphoinositide 3-kinase (PI3K)/Akt and ERK cascade. We conclude that zinc
      promotes activation and proliferation of myogenic cells, and this activation
      requires phosphorylation of PI3K/Akt and ERK as part of the signaling cascade. 

PMID- 25773776
TI  - Deletion of BRCA2 exon 27 causes defects in response to both stalled and
      collapsed replication forks.
AB  - BRCA2 is a tumor suppressor that maintains genomic integrity through double
      strand break (DSB) repair and replication fork protection. The BRC motifs and an
      exon 27-encoded domain (Ex27) of BRCA2 interact with the recombinase RAD51 to,
      respectively, facilitate the formation and stability of a RAD51 filament on
      single strand DNA. The BRC-RAD51 associations enable DSB repair while the Ex27
      RAD51 association protects the nascent replication strand from MRE11-mediated
      degradation. MRE11 is a nuclease that facilitates the generation of 3' overhangs
      needed for homologous recombination (HR)-mediated DSB repair. Here we report the
      dynamics of replication fork maintenance in mouse embryonic stem (ES) cells
      deleted for Ex27 (brca2(lex1/lex2)) after exposure to hydroxyurea (HU) that
      depletes nucleotides. HU conditions were varied from mild to severe. Mild
      conditions induce an ATR-response to replication fork stalling while severe
      conditions induce a DNA-PKCS-response to replication fork collapse and a DSB.
      These responses were differentiated by replication protein A (RPA)
      phosphorylation. We found that Ex27 deletion reduced MRE11 localization to
      stalled, but not collapsed, replication forks and that Ex27-deletion caused a
      proportionately more severe phenotype with HU dose. Therefore, the BRCA2 exon 27
      domain maintains chromosomal integrity at both stalled and collapsed replication
      forks consistent with involvement in both replication fork maintenance and double
      strand break repair. 

PMID- 25773778
TI  - Experimental evidence of Migfilin as a new therapeutic target of hepatocellular
      carcinoma metastasis.
AB  - Migfilin is a novel cell-matrix adhesion protein known to interact with
      Vasodilator Stimulated Phosphoprotein (VASP) and be localized both at cell-matrix
      and cell-cell adhesions. To date there is nothing known about its role in
      hepatocellular carcinoma (HCC). As matrix is important in metastasis, we aimed to
      investigate the Migfilin's role in HCC metastasis using two human HCC cell lines
      that differ in their metastatic potential; non-invasive Alexander cells and the
      highly invasive HepG2 cells. We silenced Migfilin by siRNA and studied its effect
      on signaling and metastasis-related cellular properties. We show that Migfilin's
      expression is elevated in HepG2 cells and its silencing leads to upregulation of
      actin reorganization-related proteins, namely phosphor-VASP (Ser157 and Ser239),
      Fascin-1 and Rho-kinase-1, promoting actin polymerization and inhibiting cell
      invasion. Phosphor-Akt (Ser473) is decreased contributing to the upregulation of
      free and phosphor-beta-catenin (Ser33/37Thr41) and inducing proliferation.
      Migfilin elimination upregulates Extracellular Signal-regulated kinase, which
      increases cell adhesion in HepG2 and reduces invasiveness. This is the first
      study to reveal that Migfilin inhibition can halt HCC metastasis in vitro,
      providing the molecular mechanism involved and presenting Migfilin as potential
      therapeutic target against HCC metastasis. 

PMID- 25773779
TI  - APOEepsilon4 increases trauma induced early apoptosis via reducing delayed
      rectifier K(+) currents in neuronal/glial co-cultures model.
AB  - Traumatic brain injury (TBI) is a commonly encountered emergency and severe
      neurosurgical injury. Previous studies have shown that the presence of the
      apolipoprotein E (APOE) epsilon4 allele has adverse outcomes across the spectrum
      of TBI severity. Our objective was to evaluate the effects of APOE alleles on
      trauma induced early apoptosis via modification of delayed rectifier K(+) current
      (Ik(DR)) in neuronal/glial co-cultures model. An ex vivo neuronal/glial co
      cultures model carrying individual APOE alleles (epsilon2, epsilon3, epsilon4) of
      mechanical injury was developed. Flow cytometry and patch clamp recording were
      performed to analyze the correlations among APOE genotypes, early apoptosis and
      Ik(DR). We found that APOEepsilon4 increased early apoptosis at 24h (p<0.05)
      compared to the ones transfected with APOEepsilon3 and APOEepsilon2. Noticeably,
      APOEepsilon4 significantly reduced the amplitude of the Ik(DR) at 24h compared to
      the APOEepsilon3 and APOEepsilon2 (p<0.05) which exacerbate Ca(2+) influx. This
      indicates a possible effect of APOEepsilon4 on early apoptosis via inhibiting
      Ik(DR) following injury which may adversely affect the outcome of TBI. 

PMID- 25773780
TI  - Context dependent non canonical WNT signaling mediates activation of fibroblasts
      by transforming growth factor-beta.
AB  - Actions of transforming growth factor-beta are largely context dependent. For
      instance, TGF-beta is growth inhibitory to epithelial cells and many tumor cell
      lines while it stimulates the growth of mesenchymal cells. TGF-beta also
      activates fibroblast cells to a myofibroblastic phenotype. In order to understand
      how the responsiveness of fibroblasts to TGF-beta would change in the context of
      transformation, we have compared the differential gene regulation by TGF-beta in
      immortal fibroblasts (hFhTERT), transformed fibroblasts (hFhTERT-LTgRAS) and a
      human fibrosarcoma cell-line (HT1080). The analysis revealed regulation of 6735,
      4163, and 3478 probe-sets by TGF-beta in hFhTERT, hFhTERT-LTgRAS and HT1080 cells
      respectively. Intriguingly, 5291 probe-sets were found to be either regulated in
      hFhTERT or hFhTERT-LTgRAS cells while 2274 probe-sets were regulated either in
      hFhTERT or HT1080 cells suggesting that the response of immortal hFhTERT cells to
      TGF-beta is vastly different compared to the response of both the transformed
      cells hFhTERT-LTgRAS and HT1080 to TGF-beta. Strikingly, WNT pathway showed
      enrichment in the hFhTERT cells in Gene Set Enrichment Analysis. Functional
      studies showed induction of WNT4 by TGF-beta in hFhTERT cells and TGF-beta
      conferred action of these cells was mediated by WNT4. While TGF-beta activated
      both canonical and non-canonical WNT pathways in hFhTERT cells, Erk1/2 and p38
      Mitogen Activated Protein Kinase pathways were activated in hFhTERT-LTgRAS and
      HT1080 cells. This suggests that transformation of immortal hFhTERT cells by SV40
      large T antigen and activated RAS caused a switch in their response to TGF-beta
      which matched with the response of HT1080 cells to TGF-beta. These data suggest
      context dependent activation of non-canonical signaling by TGF-beta. 

PMID- 25773781
TI  - A high level of clinical response is associated with improved patient-reported
      outcomes in psoriasis: analyses from a phase 2 study in patients treated with
      ixekizumab.

PMID- 25773782
TI  - Generation of antigen-specific Foxp3+ regulatory T-cells in vivo following
      administration of diabetes-reversing tolerogenic microspheres does not require
      provision of antigen in the formulation.
AB  - We have developed novel antisense oligonucleotide-formulated microspheres that
      can reverse hyperglycemia in newly-onset diabetic mice. Dendritic cells taking up
      the microspheres adopt a restrained co-stimulation ability and migrate to the
      pancreatic lymph nodes when injected into an abdominal region that is drained by
      those lymph nodes. Furthermore, we demonstrate that the absolute numbers of
      antigen-specific Foxp3+ T regulatory cells are increased only in the lymph nodes
      draining the site of administration and that these T-cells proliferate
      independently of antigen supply in the microspheres. Taken together, our data add
      to the emerging model where antigen supply may not be a requirement in "vaccines"
      for autoimmune disease, but the site of administration - subserved by lymph nodes
      draining the target organ - is in fact critical to foster the generation of
      antigen-specific regulatory cells. The implications of these observations on
      "vaccine" design for autoimmunity are discussed and summarized. 

PMID- 25773784
TI  - Plant community composition determines the strength of top-down control in a soil
      food web motif.
AB  - Top-down control of prey by predators are magnified in productive ecosystems due
      to higher sustenance of prey communities. In soil micro-arthropod food webs,
      plant communities regulate the availability of basal resources like soil
      microbial biomass. Mixed plant communities are often associated with higher
      microbial biomass than monocultures. Therefore, top-down control is expected to
      be higher in soil food webs of mixed plant communities. Moreover, higher predator
      densities can increase the suppression of prey, which can induce interactive
      effects between predator densities and plant community composition on prey
      populations. Here, we tested the effects of predator density (predatory mites) on
      prey populations (Collembola) in monoculture and mixed plant communities. We
      hypothesized that top-down control would increase with predator density but only
      in the mixed plant community. Our results revealed two contrasting patterns of
      top-down control: stronger top-down control of prey communities in the mixed
      plant community, but weaker top-down control in plant monocultures in high
      predator density treatments. As expected, higher microbial community biomass in
      the mixed plant community sustained sufficiently high prey populations to support
      high predator density. Our results highlight the roles of plant community
      composition and predator densities in regulating top-down control of prey in soil
      food webs. 

PMID- 25773783
TI  - Limit of detection of genomic DNA by conventional PCR for estimating the load of
      Staphylococcus aureus and Escherichia coli associated with bovine mastitis.
AB  - Detection of mastitis-associated bacteria can be accomplished by culturing or by
      molecular techniques. On the other hand, rapid and inexpensive methods to
      enumerate bacterial load without culturing can be better achieved by molecular
      methods. Staphylococcus aureus and Escherichia coli are the predominant bacterial
      pathogens associated with bovine mastitis. Here, we describe the application of
      conventional PCR for the limit of detection (LOD) of genomic DNA of S. aureus and
      E. coli based on single-copy genes. The selected genes were thermonuclease (nuc),
      aureolysin (aur), and staphopain A (scpA) for S. aureus and beta-D-glucuronidase
      A (uidA), cytochrome d oxidase (cyd), and rodA (a gene affecting cell shape and
      methicillin sensitivity) for E. coli. The LOD was 5.3, 15.9, and 143 pg for aur,
      nuc, and scpA genes, corresponding to S. aureus genomic copies of 1.75 * 10(3),
      5.16 * 10(3), and 4.71 * 10(4), respectively. The LOD was 0.45, 12.3 and 109 pg
      for uidA, rodA and cyd genes, corresponding to E. coli genome copies of 8.91 *
      10(1), 2.43 * 10(3), and 2.16 * 10(4), respectively. Application of uidA and aur
      PCRs to field strains revealed that as low as approximately 100 genome copies of
      E. coli and 1000-10,000 copies of S. aureus could be detected. This study is the
      first to report LOD of genomic DNA using conventional PCR for aur and scpA genes
      of S. aureus, and rodA and cyd genes of E. coli. The results should be useful for
      developing assays to assess bacterial load in milk and to determine the load that
      contributes to subclinical or clinical mastitis. 

PMID- 25773785
TI  - Association between patient activation and patient-assessed quality of care in
      type 2 diabetes: results of a longitudinal study.
AB  - BACKGROUND: Previous research using cross-sectional data has shown a positive
      relationship between patient activation and quality of care. The quantitative
      relationships in the same patients over time, however, remain undefined.
      OBJECTIVE: To examine the relationship between changes in activation over time
      and patient-assessed quality of chronic illness care. DESIGN: Prospective cohort
      study. PARTICIPANTS: The study used data reported annually from 2008 (N = 3761)
      to 2010 (N = 3040), using self-report survey questionnaires, completed by
      patients with type 2 diabetes in a population-based cohort in Queensland,
      Australia. MAIN MEASURES: Principal measures were the 13-item Patient Activation
      Measure (PAM), and the 20-item Patient Assessment of Chronic Illness Care (PACIC)
      instrument. METHODS: Nonparametric anova was used to determine the association
      between patient activation and patient-assessed quality of care in low and high
      patient activation groups at baseline (2008), and in 2009 and 2010, when patients
      had changed group membership. The Wilcoxon signed ranks test was used to compare
      the PACIC scores between baseline and each follow-up survey for the same patient
      activation level. RESULTS: Patient activation was positively associated with the
      median PACIC score within each survey year and within each of the groups defined
      at baseline (high- and low-activation groups; P < 0.001). CONCLUSIONS: Patient
      activation and the PACIC change in the same direction and should be considered
      together in the interpretation of patient care assessment. This can be carried
      out by interpreting PACIC scores within strata of PAM.

PMID- 25773787
TI  - Exploding head syndrome is common in college students.
AB  - Exploding head syndrome is characterized by the perception of loud noises during
      sleep-wake or wake-sleep transitions. Although episodes by themselves are
      relatively harmless, it is a frightening phenomenon that may result in clinical
      consequences. At present there are little systematic data on exploding head
      syndrome, and prevalence rates are unknown. It has been hypothesized to be rare
      and to occur primarily in older (i.e. 50+ years) individuals, females, and those
      suffering from isolated sleep paralysis. In order to test these hypotheses, 211
      undergraduate students were assessed for both exploding head syndrome and
      isolated sleep paralysis using semi-structured diagnostic interviews: 18.00% of
      the sample experienced lifetime exploding head syndrome, this reduced to 16.60%
      for recurrent cases. Though not more common in females, it was found in 36.89% of
      those diagnosed with isolated sleep paralysis. Exploding head syndrome episodes
      were accompanied by clinically significant levels of fear, and a minority (2.80%)
      experienced it to such a degree that it was associated with clinically
      significant distress and/or impairment. Contrary to some earlier theorizing,
      exploding head syndrome was found to be a relatively common experience in younger
      individuals. Given the potential clinical impacts, it is recommended that it be
      assessed more regularly in research and clinical settings. 

PMID- 25773786
TI  - Effects of Hydrogen Sulfide on Modulation of Theta-Gamma Coupling in Hippocampus
      in Vascular Dementia Rats.
AB  - Our previous study showed that hydrogen sulfide (H2S) could alleviate the
      cognitive deficits in vascular dementia (VD) rats associated with the improvement
      of synaptic plasticity. Neural oscillations are reported to interact with each
      other through either identical-frequency or cross-frequency coupling. This study
      examined whether impaired neural couplings could be alleviated by H2S in the
      hippocampal CA3-CA1 of VD rats and explored its possible mechanism. A VD rat
      model was established by two-vessel occlusion. Sodium hydrosulfide (NaHS), a kind
      of H2S donor, was administered intraperitoneally (5.6 mg/kg/day) for 3 weeks.
      Local field potentials were simultaneously collected in the hippocampal CA3 and
      CA1. The effects of NaHS on the modulation of theta-gamma coupling were evaluated
      by using the measurements of both phase-phase coupling and phase-amplitude
      coupling, while several other approaches including behavior, electrophysiology,
      western blot, immunofluorescence staining were also employed. The results showed
      that NaHS significantly prevented spatial learning and memory impairments (p <
      0.01). NaHS considerably alleviated the impairment of neural coupling in VD rats
      in an identical-frequency rhythm and between cross-frequency bands. Moreover, the
      expression of cystathionine-beta-synthase (CBS) was markedly attenuated in VD
      rats. NaHS elevated the expression of CBS to maintain the intrinsic balance of
      H2S. Interestingly, it was observed that NaHS increased the protein expression of
      N-methyl-D-aspartic acid receptor 2A (NMDAR2A) in VD rats. In conclusion, the
      data suggest that NaHS played the neuroprotective role partly via modulating the
      expression of NMDAR2A in order to alleviate the impairments of neural couplings
      in VD rats.

PMID- 25773788
TI  - Optical imaging biomarkers of drug-induced vascular injury.
AB  - Drug-induced vascular injury (DIVI), defined as arterial medial
      degeneration/necrosis usually associated with perivascular inflammation, is
      frequently observed in the mesenteric arteries of rats but the relevance to
      humans remains a hurdle for drug development. Here, we describe the evaluation of
      commercially available optical imaging biomarkers using a rat DIVI model. Male
      Sprague Dawley rats were administered 10 mg/kg/day of a proprietary soluble
      guanylate cyclase activator (sGCa). Optical agents, AngioSense for the detection
      of vessel permeability, MMPSense for the detection of activated matrix
      metalloproteinases (MMPs), and IntegriSense for the detection of alphavbeta3
      integrin, were injected via tail vein 24 hours before fluorescence (FL) ex vivo
      imaging. Imaging found a statistically significant difference in FL from all
      optical agents between treated and vehicle groups (p < .05). Mesenteric arteries
      were further analyzed by histopathology, flow cytometry, and
      immunohistochemistry. Histopathology confirmed perivascular inflammation and/or
      arterial medial degeneration in the sGCa-treated animals. Flow cytometry of
      digested arteries revealed myeloid cells as a main source of MMPSense signal.
      Immunohistochemical analysis further identified elevated MMP-9 expression within
      arterial walls and surrounding tissue of treated animals. Together, these data
      demonstrate that MMPSense and AngioSense are sensitive optical imaging biomarkers
      for the quantification of DIVI in rat mesenteric arteries.

PMID- 25773789
TI  - Clinical efficacy and possible applications of genomics in lung cancer.
AB  - The heterogeneous nature of lung cancer has become increasingly apparent since
      introduction of molecular classification. In general, advanced lung cancer is an
      aggressive malignancy with a poor prognosis. Activating alterations in several
      potential driver oncogenic genes have been identified, including EGFR, ROS1 and
      ALK and understanding of their molecular mechanisms underlying development,
      progression, and survival of lung cancer has led to the design of personalized
      treatments that have produced superior clinical outcomes in tumours harbouring
      these mutations. In light of the tsunami of new biomarkers and targeted agents,
      next generation sequencing testing strategies will be more appropriate in
      identifying the patients for each therapy and enabling personalized patients
      care. The challenge now is how best to interpret the results of these genomic
      tests, in the context of other clinical data, to optimize treatment choices. In
      genomic era of cancer treatment, the traditional one-size-fits-all paradigm is
      being replaced with more effective, personalized oncologic care. This review
      provides an overview of lung cancer genomics and personalized treatment. 

PMID- 25773790
TI  - Lack of participation of the GSTM1 polymorphism in cervical cancer development in
      Northeast Thailand.
AB  - The potential association between the GSTM1 deletion polymorphism and risk of
      cervical cancer was investigated in Northeastern Thailand. DNA was extracted from
      buffy coat specimens of 198 patients with squamous cell carcinoma of the cervix
      and 198 age-matched healthy controls. Genotyping of the GSTM1 was conducted by
      using two PCR methods, a short- and a long-PCR. Distribution of the GSTM1
      genotypes in between the cases and the controls was not significantly different
      (p>0.5 by chi2 test). The results suggest that the GSTM1 deletion polymorphism is
      not a risk factor for squamous cell carcinoma of the cervix in the northeast Thai
      women.

PMID- 25773791
TI  - Rs895819 within miR-27a might be involved in development of non small cell lung
      cancer in the Chinese Han population.
AB  - MicroRNA-27a (miR-27a) is deemed to be an oncogene that plays an important role
      in development of various cancers, and single nucleotide polymorphism (SNP) of
      miR-27a can influence the maturation or aberrant expression of hsa-miR27a,
      resulting in increased risk of cancer and poor prognosis for non-small cell lung
      cancer (NSCLC). This study aimed to assess the effects of rs895819 within miR-27a
      on susceptibility and prognosis of NSCLC patients in 560 clinical confirmed cases
      and 568 healthy check-up individuals. Adjusted odds/hazard ratios (ORs/HRs) and
      95% confidential intervals (CIs) were calculated to evaluate the association
      between rs895819 and the risk and prognosis of NSCLC. The results showed that
      allele A and genotype GG of rs895819 were significantly associated with an
      increased risk of NSCLC (38.9% vs 30.8%, adjusted OR=1.26, 95%CI=1.23-1.29 for
      allele G vs A; 18.1% vs 11.7%, adjusted OR=1.67, 95%CI=1.59-1.75 for genotype GG
      vs AA). Moreover, positive associations were also observed in dominant and
      recessive models (53.7% vs 49.9%, adjusted OR=1.17, 95%CI=1.13-1.20 for GG/AG vs
      AA; 18.1% vs 11.7%, adjusted=1.65, 95%CI=1.58-1.73). However, no significant
      association was found between rs895819 and the prognosis of NSCLC in genotype,
      dominant and recessive models. These results suggested that miR-27a might be
      involved in NSCLC carcinogenesis, but not in progression of NSCLC. The allele G,
      genotype GG and allele G carrier (GG/AG vs AA) of rs895819 might be genetic
      susceptible factors for NSCLC. Further multi-central, large sample size and well
      designed prospective studies as well as functional studies are warranted to
      verify our findings.

PMID- 25773792
TI  - MGMT-B gene promoter hypermethylation in patients with inflammatory bowel disease
      - a novel finding.
AB  - Inflammatory bowel disease (IBD) is a disease strongly associated with colorectal
      cancer (CRC) as a well-known precancerous condition. Alterations in DNA
      methylation and mutation in K-ras are believed to play an early etiopathogenic
      role in CRC and may also an initiating event through deregulation of molecular
      signaling. Epigenetic silencing of APC and SFRP2 in the WNT signaling pathway may
      also be involved in IBD-CRC. The role of aberrant DNA methylation in precancerous
      state of colorectal cancer (CRC) is under intensive investigation worldwide. The
      aim of this study was to investigate the status of promoter methylation of MGMT
      B, APC1A and SFRP2 genes, in inflamed and normal colon tissues of patients with
      IBD compared with control normal tissues. A total of 52 IBD tissues as well as
      corresponding normal tissues and 30 samples from healthy participants were
      obtained. We determined promoter methylation status of MGMT-B, SFRP2 and APC1A
      genes by chemical treatment with sodium bisulfite and subsequent MSP. The most
      frequently methylated locus was MGMT-B (71%; 34 of 48), followed by SFRP2 (66.6
      %; 32 of 48), and APC1A (43.7%; 21 of 48). Our study demonstrated for the first
      time that hypermethylation of the MGMT-B and the SFRP2 gene promoter regions
      might be involved in IBD development. Methylation of MGMT-B and SFRP2 in IBD
      patients may provide a method for early detection of IBD-associated neoplasia.

PMID- 25773793
TI  - Cancer detection rates in a population-based, opportunistic screening model, New
      Delhi, India.
AB  - BACKGROUND: In India, cancer accounts for 7.3% of DALY's, 14.3% of mortality with
      an age-standardized incident rate of 92.4/100,000 in men and 97.4/100,000 in
      women and yet there are no nationwide screening programs. MATERIALS AND METHODS:
      We calculated age-standardized and age-truncated (30-69 years) detection rates
      for men and women who attended the Indian Cancer Society detection centre, New
      Delhi from 2011-12. All participants were registered with socio-demographic,
      medical, family and risk factors history questionnaires, administered clinical
      examinations to screen for breast, oral, gynecological and other cancers through
      a comprehensive physical examination and complete blood count. Patients with an
      abnormal clinical exam or blood result were referred to collaborating institutes
      for further investigations and follow-up. RESULTS: A total of n=3503 were
      screened during 2011-12 (47.8% men, 51.6% women and 0.6% children <15 years) with
      a mean age of 47.8 yrs (+/-15.1 yrs); 80.5% were aged 30-69 years and 77.1% had
      at least a secondary education. Tobacco use was reported by 15.8%, alcohol
      consumption by 11.9% and family history of cancer by 9.9% of participants. Follow
      up of suspicious cases yielded 45 incident cancers (51.1% in men, 48.9% in
      women), consisting of 55.5% head and neck (72.0% oral), 28.9% breast, 6.7%
      gynecological and 8.9% other cancer sites. The age-standardized detection rate
      for all cancer sites was 340.8/100,000 men and 329.8/100,000 women. CONCLUSIONS:
      Cancer screening centres are an effective means of attracting high-risk persons
      in low-resource settings. Opportunistic screening is one feasible pathway to
      address the rising cancer burden in urban India through early detection.

PMID- 25773794
TI  - Liver cancer mortality characteristics and trends in China from 1991 to 2012.
AB  - PURPOSE: To investigate the distribution of liver cancer mortality as well as its
      developing trend from l991 to 2012, forecast the future five-year trend, and
      provide a basis for the comprehensive prevention and management. MATERIALS AND
      METHODS: Mortality data for liver cancer in China from 1991 to 2012 were used to
      describe characteristics and distribution of liver cancer mortality. Trend
      surface analysis was used to study the geographical distribution of liver cancer
      mortality. Curve estimation, time series modeling, gray modeling (GM) and
      joinpoint regression were used to predict and forecast future trends. RESULTS:
      The mortality rate of liver cancer has constantly increased in China since 1991.
      Rates in rural areas are higher than in urban areas, and in males are higher than
      in females. In addition, our data predicted that the trend will continue to
      increase in the next 5 years. The age-specific mortality of liver cancer
      increases with age and peaks in the group of 80-84 years old. Geographical
      analysis showed the liver mortality rate was higher in the southeast provinces,
      such as Jiangsu, Zhejiang and Guangdong, and southwest regions like Guangxi
      Province. CONCLUSIONS: The standardized mortality rate of liver cancer in China
      has consistently increased from 1991 to 2012, and the upward trend is predicted
      to continue in the future. Much better prevention and management of liver cancer
      is needed in high mortality areas (the southwestern and southeastern parts of
      China) and high mortality age groups (80- to 84-year-olds), especially in rural
      areas.

PMID- 25773795
TI  - Estimating radiation therapy toxicity and tolerability with comprehensive
      assessment parameters in geriatric cancer patients.
AB  - Cancer prevalance and incidence is increasing with aging of populations and age
      is a critical factor in decision-making for anti-cancer treatment. However it is
      believed that chronological age is not enough to guide management in elderly
      cancer patients. Multidisciplinary evaluation and comprehensive geriatric
      assessment has gained importance regarding the treatment selection especially for
      definitive anti-cancer therapy recently. We here aimed to analyse the effect of
      the comprehensive geriatric assessment parameters on radiotherapy toxicity and
      tolerability in a series of geriatric cancer patients in Turkey.

PMID- 25773796
TI  - Efficacy and toxicity of sunitinib in metastatic renal cell carcinoma patients in
      Egypt.
AB  - BACKGROUND: To evaluate our results in terms of response, survival and toxicity
      profile of sunitinib among Egyptian patients with metastatic renal cell
      carcinoma. MATERIALS AND METHODS: Between January 2010 and December 2013, 44
      patients with metastatic renal cell carcinoma who received sunitinib at an
      oncology center of Cairo university hospitals were enrolled in this retrospective
      analysis. RESULTS: The median age of the patients was 53 years, 22 (50%) having
      localized disease at presentation ,while the remaining half of the patients
      presented with metastasis. At a median follow up of 19 months, 9 (21%) patients
      achieved partial remission, while disease was reported stable in 20 cases (45%)
      and progressive in 7 (16%), 4 (9%) being lost to follow up, and 4 (9%) had
      discontinued therapy due to toxicity. The median overall survival was 23 months
      (95%CI 15.2 - 30.9), while progression free survival was 12 months (95%CI 11.6 -
      12.3). The most commonly reported non hematological grade 3 adverse events
      included mucositis (15.9%), hand-foot syndrome (13.6%), and fatigue (9%), while
      the predominant grade 3 or 4 laboratory abnormalities were neutropenia (6.8%),
      followed by anemia in 4.5% of patients. CONCLUSIONS: Our efficacy data were
      comparable to the published literature in terms of progression free survival and
      overall survival , while toxicity profile is different from Asian and western
      countries. However, sunitinib adverse events were manageable and tolerable in
      most of our Egyptian patients.

PMID- 25773797
TI  - VHL gene mutation analysis of a Chinese family with non- syndromic
      pheochromocytomas and patients with apparently sporadic pheochromocytoma.
AB  - OBJECTIVE: The Von Hippel-Lindau syndrome (VHLD), an inherited neoplastic
      syndrome predisposing to central nervous system hemangioblastoma (CNS),
      pheochromocytoma (PCC), renal cell carcinoma(RCC), retinal hemangioma (RA) and
      renal cysts, is caused by mutations or deletions of the VHL tumor-suppressor
      gene. To assess VHL genotype-phenotype correlations with function of pVHL a gene
      mutation analysis of members in a Chinese family with non-syndromic PCCs and
      individuals with apparently sporadic pheochromocytoma (ASP) was performed.
      MATERIALS AND METHODS: DNA samples of 20 members from the Chinese family with non
      syndromic PCCs and 41 patients with ASP were analyzed by polymerase chain
      reaction and direct sequencing, confirmed by Taqman probe. RESULTS: Three novel
      mutations (H125P, 623(?TTTGTtG) and R120T) were identified in the Chinese family
      and in 3 among 41 ASP patients. The mutations were all located in exon 2 of VHL
      gene encoding beta-domain of pVHL. The tumor type in H125P carriers and R120T
      carriers was VHL type 2C. And 623(?TTTGTtG) carriers presented VHL type 2B or
      type 2C. CONCLUSIONS: VHL gene abnormalities were identified in the Chinese
      family with non-syndromic PCCs and patients with APS, resulting in dysfunction of
      pVHL. H125P and R120T could be associated with VHL type 2C, while 623(?TTTGTtG)
      might be linked with VHL type 2B or type 2C. Not only is the genetic analysis
      helpful for early diagnosis and treatment of patients with VHLD, it is also
      benefitial for research into VHLD pathogenesis.

PMID- 25773798
TI  - Estimating the completeness of gastric cancer registration in Ardabil/Iran by a
      capture-recapture method using population-based cancer registry data.
AB  - BACKGROUND: Knowledge of cancer incidences is essential for cancer prevention and
      control programs. Capture-recapture methods have been recommended for reducing
      bias and increasing the accuracy of cancer incidence estimations. This study
      aimed to estimate the completeness of gastric cancer registration by the capture
      recapture method based on Ardabil population-based cancer registry data.
      MATERIALS AND METHODS: All new cases of gastric cancer reported by three sources,
      pathology reports, death certificates and medical records that reported to
      Ardabil population-based cancer registry in 2006 and 2008 were enrolled in the
      study. The duplicate cases based on the similarity of first name, surname and
      fathers names were identified between sources. The estimated number of gastric
      cancers was calculated by the log-linear method using Stata 12 software. RESULTS:
      A total of 857 new cases of gastric cancer were reported from three sources.
      After removing duplicates, the reported incidence rates for the years 2006 and
      2008 were 35.3 and 32.5 per 100,000 population, respectively. The estimated
      completeness calculated by log-linear method for these years was 36.7 and 36.0,
      respectively. CONCLUSIONS: These results indicate that none of the sources of
      pathology reports, death certificates and medical records individually or
      collectively fully cover the incident cases of gastric cancer. We can obtain more
      accurate estimates of incidence rates using the capture-recapture method.

PMID- 25773799
TI  - IL-1beta polymorphism and expression associated with decreased risk of gastric
      carcinoma: a case control study in the ethnic Kashmiri population, India.
AB  - The aim of this research was to investigate the possible association between
      gastric carcinoma (GC) and polymorphisms of the IL-1beta gene in the Kashmiri
      population using peripheral blood DNA from 150 gastric carcinoma cases and 250
      population controls with detailed data for clinicopathological characteristics of
      the disease. Two SNPs in the IL-1beta gene were selected for this study.
      Expression of IL-1beta was studied in 50 gastric carcinoma cases using
      immunohistochemistry and RT-PCR and then correlated with genotype. The frequency
      of the IL-1beta-511 C allele was significantly higher in the GC case group
      (53.3%) than in controls (45.4%) with an odds ratio (OR) of 0.73 and a P value of
      0.03. Multivariate regression analysis showed associations of gastric carcinoma
      with mutant form of IL-1beta-511 TT (OR 0.309; P value <0.001) and the CC
      genotype of IL-1beta-31 (OR 0.313; P value of 0.002). Haplotype analysis of IL
      1beta-31 and IL-1beta-511 showed decreased association of IL- 1beta-31 T with IL
      1beta-511 C with gastric carcinoma (OR 0.728; P value 0.03). Expression study of
      50 samples by immunohistochemistry (IHC) and RT-PCR showed association with grade
      III and stage III+IV. After correlating the expression with polymorphism no
      association was found.

PMID- 25773800
TI  - Irinotecan as a second-line chemotherapy for small cell lung cancer: a systemic
      analysis.
AB  - PURPOSE: This analysis was conducted to evaluate the efficacy and safety of
      irinotecan based regimens as second-line chemotherapy in treating patients with
      small cell lung cancer. METHODS: Clinical studies evaluating the efficacy and
      safety of irinotecan based regimens as second-line chemotherapy for patients with
      small cell lung cancer were identified using a predefined search strategy. Pooled
      response rates (RRs) of treatment were calculated. RESULTS: In irinotecan based
      regimens as second-line chemotherapy, 4 clinical studies which including 155
      patients with small cell lung cancer were considered eligible for inclusion. In
      all chemotherapy consisted of irinotecan with or without nedaplatin. Pooled
      analysis suggested that, in all patients, the pooled RR was 27.1% (42/155) in
      irinotecan based regimens. Nausea, vomiting, diarrhea and myelosuppression were
      the main side effects. No grade III or IV renal or liver toxicity was observed.
      No treatment related death occurred with the irinotecan based treatments.
      CONCLUSION: This systemic analysis suggests that irinotecan based regimens as
      second-line chemotherapy are associated with mild response rate and acceptable
      toxicity for patients with small cell lung cancer.

PMID- 25773801
TI  - P53 polymorphism at codon 72 is associated with keratocystic odontogenic tumors
      in the Thai population.
AB  - OBJECTIVE: To clarify the association between the p53 polymorphism at codon 72
      and susceptibility to the sporadic keratocystic odontogenic tumor (KCOT). DESIGN:
      One hundred KCOTs and 160 match-group healthy controls were genotyped to
      ascertain the frequency of the p53 codon 72 polymorphism using polymerase chain
      reaction-restriction fragment length polymorphism (PCR-RFLP), confirmed by direct
      sequencing. RESULTS: The frequencies of the Pro/Pro, Arg/Pro, and Arg/Arg
      genotypes were 23.8%, 49.4%, and 26.9%, respectively, in the controls, while the
      KCOT cohort demonstrated 43.0%, 39.0%, and 18.0%, respectively. Further analysis
      suggested that p53 Pro could be a KCOT-susceptible allele (OR (95%CI)=1.77 (1.22
      to 2.59), p=0.0024), with a sex-adjusted OR (95%CI) of 1.71 (1.17-2.50),
      p=0.0046. Moreover, the results indicated that p53 codon 72 Pro homozygous was
      associated with a two-fold risk of developing KCOT (adjusted OR (95%CI)
      =2.17(1.23-3.84), p=0.0062). CONCLUSIONS: The C/C genotype of P53 gene codon 72
      increases the risk of developing sporadic KCOT and may be a useful tool for
      screening and diagnostic purposes.

PMID- 25773802
TI  - Alpha-fetoprotein (AFP) elevation gastric adenocarcinoma and importance of AFP
      change in tumor response evaluation.
AB  - BACKGROUND: Elevated serum alpha-fetoprotein (AFP) levels in adults are
      considered abnormal. This parameter is used mostly in the diagnosis and follow-up
      of hepatocellular carcinomas and yolk sac tumors. Among the other rare tumors
      accompanied with elevated serum AFP levels, gastric cancer is the most common. In
      this study, we evaluated the follow-up and comparison of the treatment and marker
      response of patients with metastatic gastric cancer who had elevated serum AFP
      levels. MATERIALS AND METHODS: We performed a retrospective study, including all
      consecutive patients with advanced gastric cancer, who received systemic
      chemotherapy with elevated AFP level. RESULTS: Seventeen metastatic gastric
      cancer patients with elevated AFP levels at the time of diagnosis were evaluated.
      Fourteen (82.4%) were males and three (17.6%) were females. The primary tumor
      localization was the gastric body in 8 (76.4%), cardia in 7 (41.2%), and antrum
      in 2 (11.8%). Hepatic metastasis was observed in 13 (76.4%) at the time of
      diagnosis. When the relationship of AFP levels and carcinoembryonic antigen (CEA)
      response of the patients with their radiologic responses was evaluated, it was
      found that the radiologic response was compatible with AFP response in 16 (94.1%)
      patients and with CEA response in 12 (70.6%); however, in 5 (29.4%) patients no
      accordance was observed between radiological and CEA responses. CONCLUSIONS:
      Follow-up of AFP levels in metastatic gastric cancer patients with elevated AFP
      levels may allow prediction of early treatment response and could be more useful
      than the CEA marker for follow-up in response evaluation.

PMID- 25773803
TI  - Systematic analysis on the GSTM1 null phenotype and prostate cancer risk in
      Chinese people.
AB  - OBJECTIVE: Glutathione S-transferase M 1 (GSTM1) is implicated as a risk factor
      for prostate cancer. However, this issue is not clear in Chinese population. This
      systemic analysis was conducted to evaluate the effect of GSTM1 null genotypes on
      prostate cancer risk in Chinese. METHODS: Published studies investigating the
      associations between GSTM1 null genotypes and the risk of prostate cancer in
      China were identified by using a predefined search strategy. Main statisticals
      were pooled and estimated according to the primarily reported data. RESULTS: The
      prevalence of the GSTM1 null genotype was higher in prostate cancer patients than
      in controls, with significance. CONCLUSION: The GSTM1 null genotypes is
      associated with increased risk of prostate cancer in Chinese.

PMID- 25773804
TI  - Knowledge, attitudes and practice about pap smear test among women living in
      Bojnourd, North East of Iran: a population-based study.
AB  - BACKGROUND: The aim of the study was to assess the extent of knowledge, attitudes
      and practical behavior of women in Bojnourd conerning the Pap smear test.
      MATERIALS AND METHODS: This cross-sectional and population-based study was
      conducted with 1000 Iranian women aged 15-60 years old in Bojnourd city. In order
      to collect the data, a validated questionnaire was provided in four sections
      covering demographic information and questions about knowledge, attitude and
      practice about the Pap smear. Statistical analysis was performed with the
      Statistical Package for Social Sciences (version 17.0) applying a 0.05
      significance level. RESULTS: Evaluation of knowledge showed that 146 women
      (14.6%) had very weak, and 594 women (59.4%) had weak knowledge. In contrast,
      most of the women studied, 873 (87.3%), had a positive attitude toward the Pap
      smear test. According to the findings, 375 women (37.6%) had done this test so
      far. Findings indicated that the extent of knowledge had a meaningful
      relationship with the attitude status (p<0.0001). Also, there was a meaningful
      relationship between knowledge and practice, so that the weakest practice was
      seen in women who had weak knowledge (61.1%), (p<0.0001). CONCLUSIONS: According
      to findings of this research, most women do not have an appropriate knowledge
      about the necessity of having the Pap smear test, so that only a low percentage
      of women had undergone this test.

PMID- 25773805
TI  - Associations between vitamin D receptor (VDR) gene polymorphisms and colorectal
      cancer risk and effect modifications of dietary calcium and vitamin D in a
      Japanese population.
AB  - Much interest has been drawn to possible associations between vitamin D receptor
      (VDR) gene polymorphisms and colorectal cancer risk in conjunction with
      potentially protective effects of calcium and vitamin D. In a study of 685 cases
      of colorectal cancer and 778 community controls in Japan, we examined the
      associations of the FokI, BsmI, ApaI, and TaqI polymorphisms with colorectal
      cancer risk and effect modification by dietary calcium and vitamin D. Genotypes
      were determined by the PCR-RFLP method. The ApaI polymorphism seemed to be
      associated with a decreased risk of colorectal cancer, particularly of rectal
      cancer. The adjusted odds ratio of colorectal cancer for the ApaI AA and Aa
      genotypes combined versus the aa genotype was 0.83 (95% confidence interval [CI]
      0.67-1.02), and the corresponding value for rectal cancer was 0.75 (95%CI 0.56
      0.99). A decreased risk of colorectal cancer for the ApaI AA and Aa genotypes
      combined was more evident in individuals with high calcium intake (interaction
      p=0.055). The FokI polymorphism seemed to be associated with a decreased risk of
      colon cancer among those with high vitamin D intake (interaction p=0.09). The
      BsmI and TaqI polymorphisms were unrelated to colorectal cancer risk, and the
      null associations were not modified by calcium or vitamin D intake. In
      conclusion, the ApaI polymorphism may be associated with a decreased risk of
      colorectal cancer in Japanese, dependent on dietary calcium intake.

PMID- 25773806
TI  - Systemic analysis on laparoscope-assisted gastrectomy for patients with gastric
      cancer.
AB  - BACKGROUND: Laparoscope-assisted gastrectomy in treating patients with gastric
      cancers developed with a background of highly invasive traditional surgery and is
      being increasingly performed in the Asian Pacific area. This study systemically
      investigated the technique and clinical results for comparison with traditional
      radical subtotal gastrectomy for gastric cancers. METHODS: Clinical studies
      evaluating the effectiveness and side effects of laparoscope-assisted gastrectomy
      in treating patients with gastric cancers were identified using a predefined
      search strategy. Summary rates of effectiveness and side effects of laparoscope
      assisted gastrectomy were calculated. RESULTS: Thirteen clinical studies which
      including 1,412 patients with gastric cancer treated by laparoscope-assisted
      gastrectomy were considered eligible for inclusion. Systemic analysis showed
      that, for all patients, the pooled resection rate was 100%. Major adverse effects
      were anastomotic stenosis, abdominal abscess, abdominal bleeding, postoperative
      ileus. Treatment related death occurred in 0. 71% (10/1412). CONCLUSION: This
      systemic analysis suggests that laparoscope-assisted gastrectomy in treating
      patients with gastric cancers is associated with good curative rate and
      acceptable complications.

PMID- 25773807
TI  - Value of the platelet to lymphocyte ratio in the diagnosis of ovarian neoplasms
      in adolescents.
AB  - BACKGROUND: Relationships between poor prognosis of ovarian malignancies and
      changes in complete blood count parameters have been proposed previously. In this
      work, we aimed to evaluate clinicopathologic features in adolescents with adnexal
      masses and sought to establish any predictive value of the platelet to lymphocyte
      ratio (PLR) in diagnosis. MATERIALS AND METHODS: This retrospective study was
      conducted on 196 adolescent females with adnexal masses. Three groups were
      constituted with respect to clinical or histopathology results: group 1, non
      neoplastic patients (n:65); group 2, neoplastic patients (n:68); and group 3
      expectantly managed patients (n:63). The main parameters recorded from the
      hospital database and patient files were age, body mass index (BMI), chief
      symptoms, diameter of the mass (DOM), tumor marker levels, complete blood count
      values including absolute neutrophil, lymphocyte, and platelet counts, mean
      platelet volume, platelet distribution width, and platecrit, surgical features,
      and postoperative histopathology results. RESULTS: The expectantly managed
      patients were younger than the other groups (p=0.007). The mean body mass index
      (BMI) was higher in the neoplastic group (p=0.016). Preoperative DOM, CA125, mean
      platelet volume and PLR were statistically significantly different between the
      groups (p<0.05). ROC curve analysis demonstrated that increased PLR (AUC, 0.609;
      p=0.011) and BMI (AUC, 0.611; p=0.011) may be discriminative factors in
      predicting ovarian neoplasms in adolescents preoperatively. When the cut-off
      point for the PLR level was set to 140, the sensitivity and specificity levels
      were found to be 65.7% and 57.6%, respectively. CONCLUSIONS: We suggest that
      beside a careful preoperative evaluation including clinical characteristics,
      ultrasonographic features and tumor markers, PLR may predict ovarian neoplasms in
      adolescents.

PMID- 25773808
TI  - Preparation and characterization of anti-GP73 monoclonal antibodies and
      development of double-antibody sandwich ELISA.
AB  - BACKGROUND: Serum Golgi protein 73 (GP73) as a novel and potential marker for
      diagnosing hepatocellular carcinoma (HCC) have been found to be elevated in HCC
      patients and associated with clinical variables representing tumor growth and
      invasiveness. The aim of this study was to prepare a pair of monoclonal antibodys
      (mAbs) against GP73 and develop a newly designed double-antibody sandwich enzyme
      linked immunosorbent assay (s-ELISA), which would be used in the detection of
      serum GP73 (sGP73) as well as in the diagnosis of HCC. MATERIALS AND METHODS:
      Produced by prokaryotic expression, the purified recombinant GP73 (rGP73),
      produced by prokaryotic expression, was used to immunize the Balb/c mice. Two
      hybridoma cell lines against GP73 were obtained by fusing mouse Sp2/0 myeloma
      cells with spleen cells from the immunized mice. The titers of anti-GP73 mAb
      reached 1:243,000. Western blotting analysis and Immunohistochemistry staining
      revealed that anti-GP73 mAb could recognize GP73 protein. The double-antibody s
      ELISA was successfully established and validated by 119 HCC and 103 normal serum
      samples. RESULTS: showed that the detection limit of this method could reach 1.56
      ng/ml, and sGP73 levels in HCC group (mean=190.6 ng/ml) were much higher than
      those of in healthy controls (mean=70.92 ng/ml). CONCLUSIONS: Results of our
      study not only showed that sGP73 levels of HCC patients were significantly higher
      than those of healthy controls, but also indicated that the laboratory homemade
      anti-GP73 mAbs could be the optimal tool used in evaluating sGP73 levels, which
      would provide a solid foundation for subsequent clinical applications.

PMID- 25773809
TI  - Diagnostic and therapeutic implications of the vascular endothelial growth factor
      family in cancer.
AB  - Cancer progression is attained by uncontrolled cell division and metastasis.
      Increase in tumor size triggers different vascular channel formation to address
      cell nutritional demands. These channels are responsible for transferring of
      nutrients and gaseous to the cancer cells. Cancer vascularization is regulated by
      numerous factors including vascular endothelial growth factors (VEGFs). These
      factors play an important role during embryonic development. Members included in
      this group are VEGFA, VEGFB, VEGFC, PIGF and VEGFD which markedly influence
      cellular growth and apoptosis. Being freely diffusible these proteins act in both
      autocrine and paracrine fashions. In this review, genetic characterization these
      molecules and their putative role in cancer staging has been elaborated.
      Prognostic significance of these molecules along with different stages of cancer
      has also been summarized. Brief outline of ongoing efforts to target hot spot
      target sites against these VEGFs and their cognate limitations for therapeutic
      implications are also highlighted. 

PMID- 25773810
TI  - Nanoparticles promise new methods to boost oncology outcomes in breast cancer.
AB  - Different types of treatment are available for patients with breast cancer, the
      most being radiotherapy, chemotherapy, hormonal therapy and combination therapy.
      Recently, nanoparticles have been emerging as promising agents for cancer therapy
      and are being investigated as contrast agents, drug carriers, radiosensitizers
      and also for hyperthermia effects. In this review the focus is on approaches for
      targeted treatment of breast cancer by combining nanoparticles, chemodrugs and
      radiation. The availble data suggest the possibility of increased roles for
      combined therapy, particularly by reducing the dose of each treatment modality,
      and consequently minimizing related side effects. 

PMID- 25773811
TI  - Advances and challenges in intensity-modulated radiotherapy for nasopharyngeal
      carcinoma.
AB  - Nasopharyngeal carcinoma is an endemic disease within specific regions in the
      world. Radiotherapy is the main treatment. In recent decades, intensity-modulated
      radiation therapy has undergone a rapid evolution. Compared with two-dimensional
      radiotherapy and/or three-dimensional conformal radiotherapy, evidence has shown
      it may improve quality of life and prognosis for patients with nasopharyngeal
      carcinoma. In addition, helical tomotherapy is an emerging technology of
      intensity-modulated radiation therapy. Its superiority in dosimetric and clinical
      outcomes has been demonstrated when compared to traditional intensity-modulated
      radiation therapy. However, many challenges need to be overcome for intensity
      modulated radiation therapy of nasopharyngeal carcinoma in the future. Issues
      such as the status of concurrent chemotherapy, updating of target delineation,
      the role of replanning during IMRT, the causes of the main local failure pattern
      require settlement. The present study reviews traditional intensity-modulated
      radiation therapy, helical tomotherapy, and new challenges in the management of
      nasopharyngeal carcinoma. 

PMID- 25773812
TI  - Medication errors in chemotherapy preparation and administration: a survey
      conducted among oncology nurses in Turkey.
AB  - BACKGROUND: Medication errors in oncology may cause severe clinical problems due
      to low therapeutic indices and high toxicity of chemotherapeutic agents. We aimed
      to investigate unintentional medication errors and underlying factors during
      chemotherapy preparation and administration based on a systematic survey
      conducted to reflect oncology nurses experience. MATERIALS AND METHODS: This
      study was conducted in 18 adult chemotherapy units with volunteer participation
      of 206 nurses. A survey developed by primary investigators and medication errors
      (MAEs) defined preventable errors during prescription of medication, ordering,
      preparation or administration. The survey consisted of 4 parts: demographic
      features of nurses; workload of chemotherapy units; errors and their estimated
      monthly number during chemotherapy preparation and administration; and evaluation
      of the possible factors responsible from ME. The survey was conducted by face to
      face interview and data analyses were performed with descriptive statistics. Chi
      square or Fisher exact tests were used for a comparative analysis of categorical
      data. RESULTS: Some 83.4% of the 210 nurses reported one or more than one error
      during chemotherapy preparation and administration. Prescribing or ordering wrong
      doses by physicians (65.7%) and noncompliance with administration sequences
      during chemotherapy administration (50.5%) were the most common errors. The most
      common estimated average monthly error was not following the administration
      sequence of the chemotherapeutic agents (4.1 times/month, range 1-20). The most
      important underlying reasons for medication errors were heavy workload (49.7%)
      and insufficient number of staff (36.5%). CONCLUSIONS: Our findings suggest that
      the probability of medication error is very high during chemotherapy preparation
      and administration, the most common involving prescribing and ordering errors.
      Further studies must address the strategies to minimize medication error in
      chemotherapy receiving patients, determine sufficient protective measures and
      establishing multistep control mechanisms.

PMID- 25773813
TI  - Association between GSTP1 genotypes and hormone receptor phenotype in invasive
      ductal carcinomas of breast.
AB  - Eighty six cases of invasive ductal breast carcinomas were utilized to
      investigate GSTP1 polymorphisms in certain immunohistochemistry (IHC) subtypes of
      breast cancer with respect to ER, PR and HER2 expression. The frequency of wild
      allele homozygote, heterozygote and variant allele homozygote genotypes were
      46.5%, 52.3% and 1.16% respectively; Whereas 54.3% of the control subjects were
      GSTP1 wild type allele homozygous, 40.0% were heterozygous and 5.71% mutant
      allele homozygous. There was dramatic inverted relation between positive IHC ER
      staining and increasing grade of tumors in general (100%, 88.6%, 40.4%) and
      especially among tumors with heterozygote genotype of GSTP1 (70%, 35.4%, 22.7).
      There was increase in positive IHC HER2 staining consistent with higher grades in
      general (20%, 29.6%, 50.0%), especially among tumors with GSTP1 wild allele
      homozygote genotype (5.0%, 9.1%, 31.8%). A remarkable reverse relation was also
      observed between the fraction of IHC hormone receptor phenotype ER+/PR+/ HER2-
      and increased grade of tumors (60.0%, 45.5%, and 27.3%) especially among tumors
      with GSTP1 heterozygote genotype, and a similar link was noted regarding ER+/PR-/
      HER2- and tumor grade. There was increase in frequency of ER-/PR-/ HER2- (0.0%,
      6.8%, and 18.2%) and ER-/PR-/ HER2+ (0.0%, 4.54%, and 40.9%) consistent with the
      higher grades of tumors in general and especially GSTP1 heterozygote genotype
      tumors. As a conclusion, there is no correlation between GSTP1 polymorphism and
      increased risk of breast cancer i.e. the mutant allele is randomly distributed in
      cancer and control cases. However, there is a link between GSTP1 genotypes and
      hormone receptor expression status and certain phenotypes of breast cancer, which
      may have clinical importance. 

PMID- 25773814
TI  - MRI-guided wire localization open biopsy is safe and effective for suspicious
      cancer on breast MRI.
AB  - BACKGROUND: Magnetic resonance imaging of breast, reported to be a high
      sensitivity of 94% to 100%, is the most sensitive method for detection of breast
      cancer. The purpose of this study was to investigate our clinical experience in
      MRI-guided breast lesion wire localization in Chinese women. MATERIALS AND
      METHODS: A total of 44 patients with 46 lesions undergoing MRI-guided breast
      lesion localization were prospectively entered into this study between November
      2013 and September 2014. Samples were collected using a 1.5-T magnet with a
      special MR biopsy positioning frame device. We evaluated clinical lesion
      characteristics on pre-biopsy MRI, pathologic results, and dynamic curve type
      baseline analysis. RESULTS: Of the total of 46 wire localization excision
      biopsied lesions carried out in 44 female patients, pathology revealed fourteen
      malignancies (14/46, 30.4%) and thirty-two benign lesions (32/46, 69.6%). All
      lesions were successfully localized followed by excision biopsy and assessed for
      morphologic features highly suggestive of malignancy according to the American
      College of Radiology Breast Imaging Reporting and Data System (BI-RADS) category
      of MRI (C4a=18, C4b=17, C4c=8,C5=3). Of 46 lesions, 37 were masses and 9 were non
      mass enhancement lesions. Thirty-two lesions showed a continuous kinetics curve,
      11 were plateau and 3 were washout. CONCLUSIONS: Our study showed success in MRI
      guided breast lesion wire localization with a satisfactory cancer diagnosis rate
      of 30.4%. MRI-guided wire localization breast lesion open biopsy is a safe and
      effective tool for the workup of suspicious lesions seen on breast MRI alone
      without major complications. This may contribute to increasing the diagnosis rate
      of early breast cancer and improve the prognosis in Chinese women.

PMID- 25773815
TI  - Breast and cervical cancer knowledge and awareness among university students.
AB  - BACKGROUND: Breast and cervical cancers are the most common types of cancer in
      women worldwide. Previous studies in Asia have shown that related knowledge and
      awareness is low among female university students. The goal of this study was to
      assess breast and cervical cancer knowledge, practices, and awareness among
      female university students in Samsun,Turkey. MATERIALS AND METHODS: This research
      was a cross-sectional survey of female university students using a self
      administered. questionnaire to investigate participant awareness and knowledge of
      breast and cervical cancer. A total of 301 female university students
      participated. Descriptive statistics and chi square tests were used for data
      analysis. RESULTS: The mean age of the participants in this study was 22.0 +/-
      5.91 years. Regarding family history, 89.7 % of the students had no known
      familial history of breast cancer. Students (65.4%) had knowledge about breast
      self examination and 52.2 % of them had performed breast self examinationm while
      55.1% of them had knowledge about prevention of cervical cancer. CONCLUSIONS:
      Although the results are preliminary, the study points to an insufficient
      knowledge of university students in Samsun about breast and cervical cancer.

PMID- 25773816
TI  - Effect of paclitaxel-loaded nanoparticles on the viability of human
      hepatocellular carcinoma HepG2 cells.
AB  - OBJECTIVE: To explore effects of paclitaxel-loaded poly lactic-co-glycolic acid
      (PLGA) particles on the viability of human hepatocellular carcinoma (HCC) HepG2
      cells. MATERIALS AND METHODS: The viability of HepG2 cells was assessed using MTT
      under different concentrations of prepared paclitaxel-loaded particles and
      paclitaxel (6.25, 12.5, 25, 50, and 100 mg/L), and apoptosis was analyzed using
      Hochest33342/Annexin V-FITC/PI combined with an IN Cell Analyzer 2000. RESULTS:
      Paxlitaxel-loaded nanoparticles were characterized by narrow particle size
      distribution (158.6 nm average particle size). The survival rate of HepG2 cells
      exposed to paclitaxel-loaded PLGA particles decreased with the increase of
      concentration and time period (P<0.01 or P<0.05), the dose- and time-dependence
      indicating sustained release (P<0.05). Moreover, apoptosis of HepG2 cells was
      induced, again with an obvious dose- and time-effect relationship (P<0.05).
      CONCLUSIONS: Paclitaxel-loaded PLGA particles can inhibit the proliferation and
      induce the apoptosis of HCC HepG2 cells. This new-type of paclitaxel carrier body
      is easily made and has low cost, good nanoparticle characterization and sustained
      release. Hence, paclitaxel- loaded PLGA particles deserve to be widely
      popularized in the clinic.

PMID- 25773817
TI  - Health promoting behavior and influencing factors in Iranian breast cancer
      survivors.
AB  - BACKGROUND: The purpose of this study was to investigate the associations among
      the internal health locus of control, depression, perceived health status, self
      efficacy, social support, and health-promoting behavior in Iranian breast cancer
      survivors and to determine influential variables. MATERIALS AND METHODS: A
      predictive design was adopted. By convenient sampling the data of 262 breast
      cancer survivors in Iran were collected by questionnaires during 2014. Data were
      analyzed applying descriptive statistics, t-tests, one-way ANOVA, Pearson's
      correlation coefficients, and stepwise multiple regression. RESULTS: The internal
      health locus of control, depression, perceived health status, self efficacy,
      social support and undergoing chemotherapy all correlated significantly with the
      health-promoting lifestyle. Stepwise multiple regression analysis revealed that
      social internal health locus of control, depression, perceived health status,
      self efficacy and social support and chemotherapy accounted for about 39.8% of
      the variance in health promoting lifestyle. The strongest influence was social
      support, followed by self efficacy, perceived health status, chemotherapy and
      depression. CONCLUSIONS: The results of the study clarifed the seriousness of
      social support, self efficacy, perceived health status and depression in
      determining the health-promoting lifestyle among Iranian breast cancer survivors.
      Health professionals should concentrate on these variables in designing plans to
      promoting a healthy lifestyle.

PMID- 25773818
TI  - Novel mutations in cholangiocarcinoma with low frequencies revealed by whole
      mitochondrial genome sequencing.
AB  - BACKGROUND: Mitochondrial DNA (mtDNA) mutations have been shown to be associated
      with cancer. This study explored whether mtDNA mutations enhance
      cholangiocarcinoma (CCA) development in individuals. MATERIALS AND METHODS: The
      whole mitochondrial genome sequences of 25 CCA patient tissues were determined
      and compared to those of white blood cells from the corresponding individuals and
      12 healthy controls. The mitochondrial genome was amplified using primers from
      Mitoseq and compared with the Cambridge Reference Sequence. RESULTS: A total of
      161 mutations were identified in CCA tissues and the corresponding white blood
      cells, indicating germline origins. Sixty-five (40%) were new. Nine mutations,
      representing those most frequently observed in CCA were tested on the larger
      cohort of 60 CCA patients and 55 controls. Similar occurrence frequencies were
      observed in both groups. CONCLUSIONS: While the correspondence between the cancer
      and mitochondrial genome mutation was low, it is of interest to explore the
      functions of the missense mutations in a larger cohort, given the possibility of
      targeting mitochondria for cancer markers and therapy in the future.

PMID- 25773819
TI  - Clinical observation of three dimensional conformal radiotherapy with tamoxifen
      in treatment of postoperative malignant glioma.
AB  - OBJECTIVE: To evaluate the efficacy and adverse effects of three dimensional
      conformal radiotherapy (3D-CRT) with tamoxifen in treating patients with
      postoperative malignant glioma. PATIENTS AND METHODS: 60 patients of
      postoperative malignant glioma were randomly assigned into two groups, 30
      patients were treated with 3D-CRT plus tamoxifen (treatment group), and the other
      30 patients with 3D-CRT plus temozolomide (control group). All patients were
      radiated by 6MV X-ray, 2.0 Gy per fraction, once daily, with a total dose (DT) of
      56~60 Gy. Tamoxifen was delivered at 60 mg /m2/d, temozolomide was given at 75
      mg/m2/d. All patients were treated with concurrent radiotherapy. RESULTS: One, 2,
      3 year survival rates of treatment and control group were 63.3%, 30.0%, 23.0% and
      70.0%, 33.3%, 26.7%, respectively (chi2=0.01, 0.23, 0.09, P>0.05). The rate of
      thromboembolism in treatment group was 6.7%. CONCLUSION: Therapeutic efficacy of
      two groups was similar, but it was more cost- effective in treatment group, and
      toxicity did not increase.

PMID- 25773820
TI  - Late stage and grave prognosis of esophageal cancer in Thailand.
AB  - BACKGROUND: Esophageal cancer is one of the major health concerns in Southeast
      Asian countries, including Thailand. However, only a limited number of studies
      have been reported from this region. This study was designed to evaluate the
      prevalence, clinical characteristics and survival rate of esophageal cancer in
      Thailand. MATERIALS AND METHODS: Clinical information, histological features and
      endoscopic findings were collected from a tertiary care center in central region
      of Thailand between September 2011- November 2014 and reviewed. RESULTS: A total
      of 64 esophageal cancer patients including 58 men and 6 women with mean age of
      62.6 years were enrolled. Common presenting symptoms were dysphagia (74%),
      dyspepsia (10%) and hematemesis (8%). Mean duration of symptoms prior to
      diagnosis was 72 days. Esophageal stenosis with contact bleeding was the most
      common endoscopic finding (55.6%). The location of cancer was found in proximal
      (16%), middle (50%) and distal (34%) esophagus. Squamous cell carcinoma was far
      more common histology than adenocarcinoma (84.2% vs 10.5%). However, esophageal
      adenocarcinoma was significantly more common than squamous cell carcinoma in
      distal area of esophagus (100% vs 22.9%; p=0.0001, OR=1.6, 95%CI=1.1-2.2).
      Esophageal cancer stages 3 and 4 accounted for 35.2% and 59.3% respectively.
      Overall 2-year survival rate was 20% and only 16% in metastatic patients.
      CONCLUSIONS: Most esophageal cancer patients in Thailand have squamous cell
      carcinoma and nearly all present at advanced stage with a grave prognosis.
      Screening of high risk individuals and early detection might be important keys to
      improve the survival rate and treatment outcome in Thailand.

PMID- 25773822
TI  - Study on theoretical models of regional humanity lung cancer hazards assessment.
AB  - PURPOSE: To establish the concept of lung cancer hazard assessment theoretical
      models, evaluating the degree of lung cancer risk of Beijing for regional
      population lung cancer hazard assessment to provide a basis for technical
      support. MATERIALS AND METHODS: ISO standards were used to classify stratified
      analysis for the entire population, life cycle, processes and socioeconomic
      management. Associated risk factors were evaluated as lung cancer hazard risk
      assessment first class indicators. STUDY DESIGN: Using the above materials,
      indicators were given the weight coefficients, building lung cancer risk
      assessment theoretical models. Regional data for Beijing were entered into the
      theoretical model to calculate the parameters of each indicator and evaluate the
      degree of local lung cancer risk. RESULTS: Adopting the concept of lung cancer
      hazard assessment and theoretical models for regional populations, we established
      a lung cancer hazard risk assessment system, including 2 first indicators, 8
      secondary indicators and 18 third indicators. All indicators were given weight
      coefficients and used as information sources. Score of hazard for lung cancer was
      84.4 in Beijing. CONCLUSIONS: Comprehensively and systematically building a lung
      cancer risk assessment theoretical model for regional populations in conceivable,
      evaluating the degree of lung cancer risk of Beijing, providing technical support
      and scientific basis for interventions for prevention.

PMID- 25773821
TI  - The carcinogenic liver fluke Opisthorchis viverrini is a reservoir for species of
      Helicobacter.
AB  - There has been a strong, positive correlation between opisthorchiasis-associated
      cholangiocarcinoma and infection with Helicobacter. Here a rodent model of human
      infection with Opisthorchis viverrini was utilized to further investigate
      relationships of apparent co-infections with O. viverrini and H. pylori. A total
      of 150 hamsters were assigned to five groups: i) Control hamsters not infected
      with O. viverrini; ii) O. viverrini-infected hamsters; iii) non-O. viverrini
      infected hamsters treated with antibiotics (ABx); iv) O. viverrini-infected
      hamsters treated with ABx; and v) O. viverrini-infected hamsters treated both
      with ABx and praziquantel (PZQ). Stomach, gallbladder, liver, colonic tissue,
      colorectal feces and O. viverrini worms were collected and the presence of
      species of Helicobacter determined by PCR-based approaches. In addition, O.
      viverrini worms were cultured in vitro with and without ABx for four weeks, after
      which the presence of Helicobacter spp. was determined. In situ localization of
      H. pylori and Helicobacter-like species was performed using a combination of
      histochemistry and immunohistochemistry. The prevalence of H. pylori infection in
      O. viverrini-infected hamsters was significantly higher than that of O. viverrini
      uninfected hamsters (p<=0.001). Interestingly, O. viverrini-infected hamsters
      treated with ABx and PZQ (to remove the flukes) had a significantly lower
      frequency of H. pylori than either O. viverrini- infected hamsters treated only
      with ABx or O. viverrini-infected hamsters, respectively (p<=0.001). Quantitative
      RT-PCR strongly confirmed the correlation between intensity H. pylori infection
      and the presence of liver fluke infection. In vitro, H. pylori could be detected
      in the O. viverrini worms cultured with ABx over four weeks. In situ localization
      revealed H. pylori and other Helicobacter-like bacteria in worm gut. The findings
      indicate that the liver fluke O. viverrini in the biliary tree of the hamsters
      harbors H. pylori and Helicobacter-like bacteria. Accordingly, the association
      between O. viverrini and H. pylori may be an obligatory mutualism. 

PMID- 25773823
TI  - Knowledge and opinions regarding oral cancer among Yemeni dental students.
AB  - BACKGROUND: Oral cancer presents with high mortality rates, and the likelihood of
      survival is remarkably superior when detected early. Health care providers,
      particularly dentists, play a critical role in early detection of oral cancers
      and should be knowledgeable and skillful in oral cancer diagnosis. PURPOSE: The
      aim of the present study was to assess the current knowledge of future Yemeni
      dentists and their opinions on oral cancer. MATERIALS AND METHODS: A pretested
      self-administered questionnaire was distributed to fourth and fifth year dental
      students. Questions relating to knowledge of oral cancer, risk factors, and
      opinions on oral cancer prevention and practices were posed. RESULTS: The
      response rate was 80%. The vast majority of students identified smoking and
      smokeless tobacco as the major risk factors for oral cancer. Most of the students
      (92.6%) knew that squamous cell carcinoma is the most common form of oral cancer,
      and 85.3% were aware that tongue and floor of the mouth are the most likely
      sites. While the majority showed willingness to advise their patients on risk
      factors, only 40% felt adequately trained to provide such advice. More than 85%
      of students admitted that they need further information regarding oral cancer. As
      expected, students of the final year appeared slightly more knowledgeable
      regarding risk factors and clinical features of the disease. CONCLUSIONS: The
      findings of the present study suggest that here is a need to reinforce the
      undergraduate dental curriculum with regards to oral cancer education,
      particularly in its prevention and early detection.

PMID- 25773824
TI  - Hep88 mAb-mediated paraptosis-like apoptosis in HepG2 cells via downstream
      upregulation and activation of caspase-3, caspase-8 and caspase-9.
AB  - Hepatocellular carcinoma (HCC) is a leading cause of cancer death worldwide.
      Presently, targeted therapy via monoclonal antibodies to specific tumor
      associated antigens is being continuously developed. Hep88 mAb has proven to
      exert tumoricidal effects on the HepG2 cell via a paraptosis-like morphology. To
      verify the pathway, we then demonstrated downstream up-regulation of caspase-3,
      caspase-8 and caspase-9, assessingmRNA expression by real-time PCR and associated
      enzyme activity by colorimetric assay. Active caspase-3 determination was also
      accomplished by flow cytometry. Active caspase-3 expression was increased by
      Hep88 mAb treatment in a dose-and time-dependent manner. All of the results
      indicated that Hep88 mAb induced programmed cell death in the HepG2 cell line
      from paraptosis-like to apoptosis by downstream induction of caspases. These
      conclusions imply that Hep88mAb might be a promising tool for the effective
      treatment of HCC in the future.

PMID- 25773825
TI  - Clinical significance of upregulation of mir-196a-5p in gastric cancer and
      enriched KEGG pathway analysis of target genes.
AB  - BACKGROUND: miRNAs are relatively recently discovered cancer biomarkers which
      have important implications for cancer early diagnosis, treatment and estimation
      of prognosis. Here we focussed on expression of mir-196a-5p in gastric cancer
      tissues and cell lines so as to analyse its significance for clinicopathologic
      characteristics and generate enriched KEGG pathways clustered by target genes for
      exploring its potential roles as a biomarker in gastric cancer. MATERIALS AND
      METHODS: The expression of mir-196a-5p in poorly, moderate and well
      differentiated gastric cancer cell lines compared with GES-1 was detected by RT
      qPCR, and the expression of mir-196a-5p in gastric cancer tissues comparing with
      adjacent non cancer tissues of 58 cases were also assessed by RT- qPCR.
      Subsequently, an analysis of clinical significance of mir-196a-5p in gastric
      cancer and enriched KEGG pathways was executed based on the miRWalk prediction
      database combined with bioinformatics tools DAVID 6.7 and Mirfocus 3.0. RESULTS:
      RT-qPCR showed that mir-196a-5p was up-regulated in 6 poorly and moderate
      differentiated gastric cancer cell lines SGC-7901, MKN-45, MKN-28, MGC-803, BGC
      823, HGC-27 compared with GES-1, but down-regulated in the highly differentiated
      gastric cancer cell line AGS. Clinical data indicated mir-196a-5p to beup
      regulated in gastric cancer tissues (47/58). Overexpression of mir-196a-5p was
      associated with more extensive degree of lymph node metastasis and clinical stage
      (P <0.05; x2 test). Enriched KEGG pathway analyses of predicted and validated
      targets in miRWalk combined with DAVID 6.7 and Mirfocus 3.0 showed that the
      targeted genes regulated by mir-196a-5p were involved in malignancy associated
      biology. CONCLUSIONS: Overexpression of mir-196a-5p is associated with lymph node
      metastasis and clinical stage, and enriched KEGG pathway analyses showed that
      targeted genes regulated by mir-196a-5p may contribute to tumorgenesis,
      suggesting roles as an oncogenic miRNA biomarker in gastric cancer.

PMID- 25773826
TI  - Non-alcoholic fatty liver disease (NAFLD) and significant hepatic fibrosis
      defined by non-invasive assessment in patients with type 2 diabetes.
AB  - BACKGROUND: Non-alcoholic fatty liver disease (NAFLD), the most common liver
      problem in diabetes, is a risk factor for liver cancer. Diabetes, high body mass
      index (BMI) and old age can all contribute to NAFLD progression. Transient
      elastography (TE) is used for non-invasive fibrosis assessment. OBJECTIVES: To
      identify the prevalence of NAFLD and significant hepatic fibrosis in diabetic
      patients and to assess associated factors. MATERIALS AND METHODS: One hundred and
      forty-one diabetic and 60 normal subjects were screened. Fatty liver was
      diagnosed when increased hepatic echogenicity and vascular blunting were detected
      by ultrasonography. Liver stiffness measurement (LSM) representing hepatic
      fibrosis was assessed by TE. LSM >=7 kPa was used to define significant hepatic
      fibrosis. RESULTS: Four cases were excluded due to positive hepatitis B viral
      markers and failed TE. Diabetic patients had higher BMI, systolic blood pressure,
      waist circumference and fasting glucose levels than normal subjects. Fatty liver
      was diagnosed in 82 (60.7%) diabetic patients but in none of the normal group.
      BMI (OR: 1.31; 95%CI: 1.02-1.69; p=0.038) and alanine aminotransferase (ALT)(OR:
      1.14; 95%CI: 1.05-1.23; p=0.002) were associated with NAFLD. Diabetic patients
      with NAFLD had higher LSM than those without [5.99 (2.4) vs 4.76 (2.7) kPa,
      p=0.005)]. Significant hepatic fibrosis was more common in diabetic patients than
      in normal subjects [22 (16.1%) vs 1 (1.7%), p=0.002]. Aspartate aminotransferase
      (AST)(OR: 1.24; 95%CI: 1.07-1.42; p=0.003) was associated with significant
      hepatic fibrosis. CONCLUSIONS: Sixty and sixteen percent of diabetic patients
      were found to have NAFLD and significant hepatic fibrosis. High BMI and ALT
      levels are the predictors of NAFLD, and elevated AST level is associated with
      significant hepatic fibrosis.

PMID- 25773827
TI  - Relationships between social support and social image concerns in Turkish women
      with breast cancer.
AB  - BACKGROUND: Breast cancer is one of the most common cancer types in women and is
      amongst the most devastating and stressful events in the life of women. The
      external appearance of breast cancer patients usually changes due to the surgical
      and/or medical therapies used. An association may be found between social support
      perception and social appearance anxiety in patients with breast cancer in the
      period after mastectomy. Therefore, this study investigated the social appearance
      anxiety and social support status in women with breast cancer in our country.
      MATERIALS AND METHODS: A descriptive cross-sectional study was conducted in
      breast cancer patients undergoing treatment or follow-up in Medical Oncology and
      General Surgery departments. RESULTS: The mean age of the participants was 51.13
      +/- 8.48 years (range, 24-74 years) with nearly half of the patients (40.6%) aged
      40-50 years. Of the patients, 39.1% had stage 3 breast cancer. The mean score on
      Cancer Patient's Social Support Scale (CPSSS) was 134.85 +/- 9.35, and there was
      a significant difference in CPSSS total scores between the age groups,
      educational levels, self-reported income levels and stage of disease (p<0.05).
      The mean Social Image Anxiety Scale (SIAS) score was found to be 34.30 +/- 9.35
      (min:16, max:66) in women participating in this study. The CPSSS and SIAS scores
      of the participants were inversely correlated, and the SIAS score was found to
      decrease with the increasing CPSSS score but with no statistically significant
      difference (r=-0.110, p=0.217). CONCLUSIONS: Social appearance anxiety is higher
      in the patients with poor social support.

PMID- 25773828
TI  - Prognostic role of hepatoma-derived growth factor in solid tumors of Eastern
      Asia: a systematic review and meta- analysis.
AB  - Hepatoma-derived growth factor (HDGF) is a novel jack-of-all-trades in cancer.
      Here we quantify the prognostic impact of this biomarker and assess how
      consistent is its expression in solid tumors. A comprehensive search strategy was
      used to search relevant literature updated on October 3, 2014 in PubMed, EMBASE
      and WEB of Science. Correlations between HDGF expression and clinicopathological
      features or cancer prognosis was analyzed. All pooled HRs or ORs were derived
      from random-effects models. Twenty-six studies, primarily in Eastern Asia,
      covering 2,803 patients were included in the analysis, all of them published
      during the past decade. We found that HDGF overexpression was significantly
      associated with overall survival (OS) (HROS=2.35, 95%CI=2.04-2.71, p<0.001) and
      disease free survival (DFS) (HRDFS=2.25, 95%CI =1.81-2.79, p<0.001) in solid
      tumors, especially in non-small cell lung cancer, hepatocellular carcinoma and
      cholangiocarcinoma (CCA). Moreover, multivariate survival analysis showed that
      HDGF overexpression was an independent predictor of poor prognosis (HROS=2.41,
      95%CI: 2.02-2.81, p<0.001; HRDFS=2.39, 95%CI: 1.77-3.24, p<0.001). In addition,
      HDGF overexpression was significantly associated with tumor category (T3-4 versus
      T1-2, OR=2.12, 95%CI: 1.17-3.83, p=0.013) and lymph node status (N+ versus N-,
      OR=2.37, 95%CI: 1.31-4.29, p=0.03) in CCA. This study provides a comprehensive
      examination of the literature available on the association of HDGF overexpression
      with OS, DFS and some clinicopathological features in solid tumors. Meta-analysis
      results provide evidence that HDGF may be a new indicator of poor cancer
      prognosis. Considering the limitations of the eligible studies, other large-scale
      prospective trials must be conducted to clarify the prognostic value of HDGF in
      predicting cancer survival. 

PMID- 25773829
TI  - Importance of neutrophil/lymphocyte ratio in prediction of PSA recurrence after
      radical prostatectomy.
AB  - BACKGROUND: The aim of this study was to research the importance of the
      neutrophil to lymphocyte ratio (NLR) in prediction of PSA recurrence after
      radical prostatectomy, which has not been reported so far. MATERIALS AND METHODS:
      The data of 175 patients who were diagnosed with localised prostate cancer and
      underwent retropubic radical prostatectomy was retrospectively examined. Patient
      pre-operative hemogram parameters of neutrophil count, lymphocyte count and NLR
      were assessed. The patients whose PSAs were too low to measure after radical
      prostatectomy in their follow-ups, and then had PSAs of 0,2 ng/mL were considered
      as patients with PSA recurrence. Patients with recurrence made up Group A and
      patients without recurrence made up Group B. RESULTS: In terms of the power of
      NLR value in distinguishing recurrence, the area under OCC was statistically
      significant (p<0.001) .The value of 2.494 for NLR was found to be a cut-off value
      which can be used in order to distinguish recurrence according to Youden index.
      According to this, patients with a higher NLR value than 2.494 had higher rates
      of PSA recurrence with 89.7% sensitivity and 92.6% specificity. CONCLUSIONS:
      There are certain parameters used in order to predict recurrence with today's
      literature data.We think that because NLR is easy to use in clinics and
      inexpensive, and also has high sensitivity and specificity values, it has the
      potential to be one of the parameters used in order to predict biochemical
      recurrence in future.

PMID- 25773830
TI  - Evaluation of hemoglobin A1c levels in endometrial cancer patients: a
      retrospective study in Turkey.
AB  - BACKGROUND: Hemoglobin A1c(HgA1c) is a marker of poor gylcemic control and
      elevation HgA1c is associated with increased risk of many cancers. We aimed to
      determine the HgA1c levels in endometrial cancer cases and any relationship with
      stage and grade of disease. MATERIALS AND METHODS: A retrospective data review
      was performed between June 2011 and October 2012 at a tertiary referral center in
      Turkey. The study included 35 surgically staged endometrial cancer patients and
      40 healthy controls. Preoperative HgA1c levels drawn within 3 months before
      surgery were compared. Also the relationships between HgA1c levels and stage,
      grade and hystologic type of cancer cases were evaluated. RESULTS: The mean HgA1c
      levels were statistically significantly higher at 6.19 +/- 1.44 in endometrial
      cancer cases than the 5.61 +/- 0.58 in controls (p=0.027). With endometrial
      cancer cases, the mean HgA1c level was found to be 6.62 +/- 1.40 for stage I and
      6.88 +/- 1.15 for stages II-IV (p=0.07). The figures were 6.74 +/- 1.65 for
      endometrioid and 6.63 +/- 1.41 for non-endometrioid type tumors (p=0.56). Mean
      HgA1c levels of 6.72 +/- 1.14 for grade 1 and 6.62 +/- 1.42 for grade 2-3 were
      observed (p=0.57). CONCLUSIONS: HgA1c levels in endometrial cancer patients were
      statistically higher than healthy controls. However, HgA1c did not show any
      significant correlation with stage, grade and histologic type in endometrial
      cancer cases.

PMID- 25773831
TI  - Association between the NQO1 C609T polymorphism with hepatocellular carcinoma
      risk in the Chinese population.
AB  - BACKGROUND: Associations between the NQO1 C609T polymorphism and hepatocellular
      carcinoma (HCC) risk are a subject of debate. We therefore performed the present
      meta-analysis to evaluate links with HCC susceptibility. MATERIALS AND METHODS:
      Several major databases (PubMed, EBSCO), the Chinese national knowledge
      infrastructure (CNKI) and the Wanfang database were searched for eligible
      studies. Crude odds ratios (ORs) with 95% confidence intervals (CIs) were used to
      measure the strength of associations. RESULTS: A total of 4 studies including
      1,325 patients and 1,367 controls were identified. There was a significant
      association between NQO1 C609T polymorphism and HCC for all genetic models
      (allelic model: OR=1.45, 95%CI=1.23-1.72, p<0.01; additive model: OR=1.96,
      95%CI=1.57-2.43, p<0.01; dominant model: OR=1.62, 95%CI=1.38-1.91, p<0.01; and
      recessive model: OR=1.53, 95%CI=1.26-1.84, p<0.01). On subgroup analysis,
      similarly results were identified in Asians. For Asians, the combined ORs and 95%
      CIs were (allelic model: OR=1.50, 95%CI=1.24-1.82, p<0.01; additive model:
      OR=2.11, 95%CI=1.48-3.01, p<0.01; dominant model: OR=1.69, 95%CI=1.42-2.02,
      p<0.01; and recessive model: OR=1.59, 95%CI=1.16-2.19, p<0.01). CONCLUSIONS: The
      current meta-analysis suggested that the NQO1 C609T polymorphism could be a risk
      factor for developing HCC, particularly in the Chinese population.

PMID- 25773832
TI  - Conditional PTEN-deficient mice as a prostate cancer chemoprevention model.
AB  - BACKGROUND: We generated a mouse model of prostate cancer based on the adult
      prostate-specific inactivation of phosphatase and tensin homolog (PTEN) using the
      Cre-loxP system. The potential of our mice as a useful animal model was examined
      by evaluating the chemopreventive efficacy of the anti-androgen, chlormadinone
      acetate (CMA). MATERIALS AND METHODS: Six-week-old mice were treated
      subcutaneously with 50 MUg/g of CMA three times a week for 9 or 14 weeks and
      sacrificed at weeks 15 and 20. Macroscopic change of the entire genitourinary
      tract (GUT) and histologically evident prostate gland tumor development were
      evaluated. Proliferation and apoptosis status in the prostate were examined by
      immunohistochemistry. RESULTS: CMA triggered significant shrinkage of not only
      the GUT but also prostate glands at 15 weeks compared to the control (p=0.017 and
      p=0.010, respectively), and the trend became more marked after a further five
      weeks of treatment. The onset of prostate adenocarcinoma was not prevented but
      the proliferation of cancer cells was inhibited by CMA, which suggested the
      androgen axis is critical for cancer growth in these mice. CONCLUSIONS:
      Conditional PTEN-deficient mice are useful as a preclinical model for
      chemoprevention studies and serve as a valuable tool for the future screening of
      potential chemopreventive agents.

PMID- 25773833
TI  - Enterocarpam-III induces human liver and breast cancer cell apoptosis via
      mitochondrial and caspase-9 activation.
AB  - An aristolactam-type alkaloid, isolated from Orophea enterocarpa, is enterocarpam
      III (10-amino-2,3,4,6- tetramethoxyphenanthrene-1-carboxylic acid lactam). It is
      cytotoxic to various human and murine cancer cell lines; however, the molecular
      mechanisms remain unclear. The aims of this study were to investigate cytotoxic
      effects on and mechanism (s) of human cancer cell death in human hepatocellular
      carcinoma HepG2 and human invasive breast cancer MDA-MB-231 cells compared to
      normal murine fibroblast NIH3T3 cells. Cell viability was determined by MTT assay
      to determine IC10, IC20 and IC50 levels, reactive oxygen species (ROS) production
      with 2',7'-dichlorohydrofluorescein diacetate and the caspase-3, -8 and -9
      activities using specific chromogenic (p-nitroaniline) tetrapeptide substrates,
      viz., DEVD-NA, IETD-NA and LEHD-NA and employing a microplate reader.
      Mitochondrial transmembrane potential (MTP) was measured by staining with 3, 3'
      dihexyloxacarbocyanine iodide (DiOC6) and using flow cytometry. The compound was
      cytotoxic to HepG2 and MDA-MB-231 cells with the IC50 levels of 26.0+/-4.45 and
      51.3+/-2.05 MUM, respectively. For murine normal fibroblast NIH3T3 cells, the
      IC50 concentration was 81.3+/-10.1 MUM. ROS production was reduced in a dose
      response manner in HepG2 cells. The caspase-9 and -3 activities increased in a
      concentration-dependent manner, whereas caspase-8 activity did not alter,
      indicating the intrinsic pathway activation. Enterocarpam-III decreased the
      mitochondrial transmembrane potential (MTP) dose-dependently in HepG2 cells,
      suggesting that the compound induced HepG2 cell apoptosis via the mitochondrial
      pathway. In conclusion, enterocarpam-III inhibited HepG2 and MDA-MB-231 cell
      proliferation and induced human HepG2 cells to undergo apoptosis via the
      intrinsic (mitochondrial) pathway and induction of caspase-9 activity.

PMID- 25773834
TI  - Expression of microRNA-218 and its clinicopathological and prognostic
      significance in human glioma cases.
AB  - BACKGROUND: MicroRNAs are a class of noncoding RNAs which regulate multiple
      cellular processes during tumor development. The purpose of this report is to
      investigate the clinicopathological and prognostic significance of miR-218 in
      human gliomas. MATERIALS AND METHODS: Quantitative RT-PCR (qRT-PCR) was conducted
      to detect the expression of miR-218 in primary normal human astrocytes, three
      glioma cell lines and 98 paired glioma and adjacent normal brain
      tissues.Associations of miR-218 with clinicopathological variables of glioma
      patients were statistically analyzed. Finally, a survival analysis was performed
      using the Kaplan-Meier method and Cox's proportional hazards model. RESULTS: The
      expression level of miR-218 in primary normal human astrocytes was significantly
      higher than that in glioma cell lines (p<0.01). Also, the expression level of miR
      218 in glioma tissues was significantly downregulated in comparison with that in
      the adjacent normal brain tissues (p<0.001). Statistical analyses demonstrated
      that low miR-218 expression was closely associated with advanced WHO grade
      (p=0.002) and low Karnofsky performance score (p=0.010) of glioma patients.
      Kaplan-Meier analysis with the log-rank test showed that patients with low-miR
      218 expression had poorer disease-free survival and overall survival (p=0.0045
      and 0.0124, respectively). Multivariate analysis revealed that miR-218 expression
      was independently associated with the disease-free survival (p=0.009) and overall
      survival (p=0.004) of glioma patients. CONCLUSIONS: Our results indicate that miR
      218 is downregulated in gliomas and that its status might be a potential valuable
      biomarker for glioma patients.

PMID- 25773835
TI  - Years of potential life lost and productivity costs due to premature cancer
      related mortality in Iran.
AB  - BACKGROUND: Cancer is recently one of the major concerns of the public health
      both in the world and Iran. To inform priorities for cancer control, this study
      estimated years of potential life lost (YPLL) and productivity losses due to
      cancer-related premature mortality in Iran in 2012. MATERIALS AND METHODS: The
      number of cancer deaths by sex for all cancers and the ten leading causes of
      cancer deaths in Iran in 2012 were obtained from the GLOBOCAN database. The life
      expectancy method and the human capital approach were used to estimate the YPLL
      and the value of productivity lost due to cancer-related premature mortality.
      RESULTS: There were 53,350 cancer-related deaths in Iran. We estimated that these
      cancer deaths resulted in 1,112,680 YPLL in total, 563,332 (50.6%) in males and
      549,348 (49.4%) in females. The top 10 ranked cancers accounted for 75% of total
      death and 70% of total YPLL in the males and 69% for both death and YPLL in the
      females. The largest contributors for YPLL in the two genders were stomach and
      breast cancers, respectively. The total cost of lost productivity due to cancer
      related premature mortality discounted at 3% rate in Iran, was US$ 1.93 billion.
      The most costly cancer for the males was stomach, while for the females it was
      breast cancer. The percentage of the total costs that were attributable to the
      top 10 cancers was 67% in the males and 71% in the females. CONCLUSIONS: The YPLL
      and productivity losses due to cancer-related premature mortality are substantial
      in Iran. Setting resource allocation priorities to cancers that occur in younger
      working-age individuals (such as brain and central nervous system) and/or cancers
      with high incidence and mortality rates (such as stomach and breast) could
      potentially decrease the productivity losses and the YPLL to a great extent in
      Iran.

PMID- 25773836
TI  - MicroRNA expression profile in patients with stage II colorectal cancer: a
      Turkish referral center study.
AB  - BACKGROUND: There are increasing data about microRNAs (miRNA) in the literature,
      providing abundant evidence that they play important roles in pathogenesis and
      development of colorectal cancer. In this study, we aimed to investigate the
      miRNA expression profiles in surgically resected specimens of patients with
      recurrent and non-recurrent colorectal cancer. MATERIALS AND METHODS: The study
      population included 40 patients with stage II colorectal cancer (20 patients with
      recurrent tumors, and 20 sex and age matched patients without recurrence), who
      underwent curative colectomy between 2004 and 2011 without adjuvant therapy.
      Expression of 16 miRNAs (miRNA-9, 21, 30d, 31, 106a, 127, 133a, 133b, 135b, 143,
      145, 155, 182, 200a, 200c, 362) was verified by quantitative real-time polymerase
      chain reaction (qRT-PCR) in all resected colon cancer tissue samples and in
      corresponding normal colonic tissues. Data analyses were carried out using SPSS
      15 software. Values were statistically significantly changed in 40 cancer tissues
      when compared to the corresponding 40 normal colonic tissues (p<0.001). MiR-30d,
      miR-133a, miR-143, miR-145 and miR-362 expression was statistically significantly
      downregulated in 40 resected colorectal cancer tissue samples (p<0.001). When we
      compared subgroups, miRNA expression profiles of 20 recurrent cancer tissues were
      similar to all 40 cancer tissues. However in 20 non-recurrent cancer tissues, miR
      133a expression was not significantly downregulated, moreover miR-133b expression
      was significantly upregulated (p<0.05). CONCLUSIONS: Our study revealed
      dysregulation of expression of ten miRNAs in Turkish colon cancer patients. These
      miRNAs may be used as potential biomarkers for early detection, screening and
      surveillance of colorectal cancer, with functional effects on tumor cell
      behavior.

PMID- 25773837
TI  - Significant association of alpha-methylacyl-CoA racemase gene polymorphisms with
      susceptibility to prostate cancer: a meta-analysis.
AB  - BACKGROUND: Alpha-methylacyl-CoA racemase(AMACR) is thought to play key roles in
      diagnosis and prognosis of prostate cancer. However, studies of associations
      between AMACR gene polymorphisms and prostate cancer risk reported inconsistent
      results. Therefore, we conducted the present meta-analysis to clarify the link
      between AMACR gene polymorphisms and prostate cancer risk. MATERIALS AND METHODS:
      A literature search was performed in PubMed, Embase, China National Knowledge
      Infrastructure (CNKI), Wanfang and Weipu databases. Odds ratios (ORs) and 95%
      confidence intervals (95%CIs) were calculated to assess the strength of any
      association between AMACR polymorphisms and prostate cancer risk. Subgroup
      analyses by ethnicity, source of controls, quality control and sample size were
      also conducted. RESULTS: Five studies covering 3,313 cases and 3,676 controls on
      five polymorphisms (D175G, M9V, S201L, K277E and Q239H) were included in this
      meta-analysis. Significant associations were detected between prostate cancer and
      D175G (dominant model: OR=0.89, 95%CI=0.80-0.99, P=0.04) and M9V (dominant model:
      OR=0.87, 95%CI=0.78-0.97, P=0.01) polymorphisms as well as that in subgroup
      analyses. We also observed significant decreased prostate cancer risk in the
      dominant model (OR=0.90, 95%CI=0.81-0.99, P=0.04) for the S201L polymorphism.
      However, K277E and Q239H polymorphisms did not appear to be related to prostate
      cancer risk. CONCLUSIONS: The current meta- analysis indicated that D175G and M9V
      polymorphisms of the AMACR gene are related to prostate cancer. The S201L
      polymorphism might also be linked with prostate cancer risk to some extent.
      However, no association was observed between K277E or Q239H polymorphisms and
      susceptibility to prostate cancer.

PMID- 25773838
TI  - Identifying social characteristics of health-related information seeker: a gender
      specific approach for cancer survivors.
AB  - While health information-seeking behavior as an indicator of health communication
      of patients including cancer survivors has been researched, few studies have
      focused on how socioeconomic position and media use combine to influence health
      related information seekers. This study examined social characteristics of health
      information-seeking behavior taking into account an individual's socioeconomic
      position and their media use in Korea, a developed country. The data for this
      study came from a survey of 1,010 respondents drawn from a nationally
      representative sample in the Republic of Korea. We conducted multivariate
      logistic regression analyses for gender-specific effects. We found that men who
      reported high household income were one and half times more likely to seek health
      information than those with low income status. We also found that women who
      performed Internet searches by computer at home were almost two times more likely
      to seek health information than those who did not. Similar results were found for
      men as well. Our analyses revealed that socioeconomic position and media use are
      associated with health information-seeking behavior by gender. Studies on
      information seekers may bring us more effective health promotion and relevant
      intervention for people with chronic conditions including cancer survivors. 

PMID- 25773839
TI  - High resolution melting curve assay for detecting rs12979860 IL28B polymorphisms
      involved in response of Iranian patients to chronic hepatitis C treatment.
AB  - BACKGROUND: A recent genome-wide association study (GWAS) on patients with
      chronic hepatitis C (CHC) treated with peginterferon and ribavirin (pegIFN
      alpha/RBV) identified a single nucleotide polymorphism (SNP) on chromosome 19
      (rs12979860) which was strongly associated with a sustained virological response
      (SVR). The aim of this study was twofold: to study the relationship between IL28B
      rs12979860 and sustained virological response (SVR) to pegIFN-alpha/RVB therapy
      among CHC patients and to detect the rs12979860 polymorphism by high resolution
      melting curve (HRM) assay as a simple, fast, sensitive, and inexpensive method.
      MATERIALS AND METHODS: The study examined outcomes in 100 patients with chronic
      hepatitis C in 2 provinces of Iran from December 2011 to June 2013. Two methods
      were applied to detect IL28B polymorphisms: PCR-sequencing as a gold standard
      method and HRM as a simple, fast, sensitive, and inexpensive method. RESULTS: The
      frequencies of IL28B rs12979860 CC, CT, and TT alleles in chronic hepatitis C
      genotype 1a patients were 10% (10/100), 35% (35/100), and 6% (6/100) and in
      genotype 3a were 13% (13/100), 31% (31/100), and 5% (5/100), respectively. In
      genotype 3a infected patients, rs12979860 (CC and CT alleles) and in genotype 1a
      infected patients (CC allele) were significantly associated with a sustained
      virological response (SVR). The SVR rates for CC, CT and TT (IL28B rs12979860)
      were 18%, 34% and 4%, respectively. Multiple logistic regression analysis
      identified two independent factors that were significantly associated with SVR:
      IL-28B genotype (rs 12979860 CC vs TT and CT; odds ratio [ORs], 7.86 and 4.084,
      respectively), and HCV subtype 1a (OR, 7.46). In the present study, an
      association between SVR rates and IL28B polymorphisms was observed. CONCLUSIONS:
      The HRM assay described herein is rapid, inexpensive, sensitive and accurate for
      detecting rs12979860 alleles in CHC patients. This method can be readily adopted
      by any molecular diagnostic laboratory with HRM capability and will be clinically
      beneficial in predicting treatment response in HCV genotype 1 and 3 infected
      patients. In addition, it was demonstrated that CC and CT alleles in HCV-3a and
      the CC allele in HCV-1a were significantly associated with response to pegIFN
      alpha/RBV treatment. The present results may help identify subjects for whom the
      therapy might be successful.

PMID- 25773840
TI  - Prognostic impact of elevation of vascular endothelial growth factor family
      expression in patients with non-small cell lung cancer: an updated meta-analysis.
AB  - BACKGROUND: The vascular endothelial growth factor family has been implicated in
      tumorigenesis and metastasis. The prognostic value of each vascular endothelial
      growth factor family member, particular VEGF/ VEGFR co-expression, in patients
      with non-small lung cancer remains controversial. MATERIALS AND METHODS: Relevant
      literature was identified by searching PubMed, EMBASE and Web of Science. Studies
      evaluating expression of VEGFs and/or VEGFRs by immunohistochemistry or ELISA in
      lung cancer tissue were eligible for inclusion. Hazard ratios (HRs) and 95%
      confidence intervals (CIs) from individual study were pooled by using a fixed- or
      random-effect model, heterogeneity and publication bias analyses were also
      performed. RESULTS: 74 studies covering 7,631 patients were included in the meta
      analysis. Regarding pro-angiogenesis factors, the expression of VEGFA (HR=1.633,
      95%CI: 1.490-1.791) and VEGFR1 (HR=1.924, 95%CI: 1.220-3.034) was associated
      separately with poor survival. Especially, VEGFA over-expression was an
      independent prognostic factor in adenocarcinoma (ADC) (HR=1.775, 95%CI: 1.384
      2.275) and SCC (HR=2.919, 95%CI: 2.060-4.137). Co-expression of VEGFA/VEGFR2
      (HR=2.011, 95%CI: 1.405-2.876) was also significantly associated with worse
      survival. For lymphangiogenesis factors, the expression of VEGFC (HR=1.611,
      95%CI: 1.407-1.844) predicted a poor prognosis. Co-expression of VEGFC/VEGFR3
      (HR=2.436, 95%CI: 1.468-4.043) emerged as a preferable prognostic marker.
      CONCLUSIONS: The expression of VEGFA (particularly in SCC and early stage NSCLC),
      VEGFC, VEGFR1 indicates separately an unfavorable prognosis in patients with
      NSCLC. Co-expression VEGFA/ VEGFR2 is comparable with VEGFC/VEGFR3, both
      featuring sufficient discrimination value as preferable as prognostic biologic
      markers.

PMID- 25773841
TI  - Acute toxicity in nasopharyngeal carcinoma patients treated with IMRT/VMAT.
AB  - PURPOSE: To evaluate acute toxicity in nasopharyngeal cancer (NPC) patients
      treated with intensity modulated radiotherapy (IMRT)/volumetric modulated arc
      therapy (VMAT) with or without cisplatin-based chemotherapy. MATERIALS AND
      METHODS: A total of 45 newly diagnosed, histologically proven non-metastatic NPC
      patients treated with IMRT between May 2010 and December 2012, were evaluated
      retrospectively, 37 planned with Eclipse and 8 with Prowess Panther treatment
      planning system. The doses to the planning target volumes of primary tumor and
      involved lymph nodes, high risk region, and uninvolved regional nodal areas were
      70 Gy, 60 Gy, and 54 Gy respectively and delivered simultaneously over 33
      fractions to 39 patients. Another 6 patients irradiated with sequential boost
      technique. Some 84.4% of patients received chemotherapy. Acute toxicities were
      graded according to the Radiation Therapy Oncology Group scoring criteria and
      Common Terminology Criteria for Adverse Events (CTCAE) for chemotherapy side
      effects. RESULTS: Median age was 43 years (14-79) and all patients were WHO type
      II. Grade 1 mucositis and dysphagia were observed in 17 (37.8%), and 10 (22.2%)
      patients, respectively. The incidence of acute grade 2 mucositis and dysphagia
      was 55.6% and 68.9%, respectively. The most common chemoradiotherapy related
      acute toxicities were nausea, leucopenia and thrombocytopenia. Grade 3 toxicity
      was detected in 13 (28.8%) cases. No grade 4 toxicity was occurred. Mean weight
      loss was 9%. None of the patients required the insertion of percutaneous
      endoscopic gastrostomy for nutritional support. Radiation therapy was completed
      without interruption in all patients. CONCLUSIONS: IMRT is a safe and effective
      treatment modality, and well tolerated by patients in the treatment of
      nasopharyngeal carcinoma. No unexpected side effects were observed.

PMID- 25773842
TI  - Prognostic factors in patients with non-small cell lung carcinoma and brain
      metastases: a Malaysian perspective.
AB  - BACKGROUND: Brain metastases occur in about 20-40% of patients with non-small
      cell lung carcinoma (NSCLC), and are usually associated with a poor outcome.
      Whole brain radiotherapy (WBRT) is widely used but increasingly, more aggressive
      local treatments such as surgery or stereotactic radiosurgery (SRS) or
      stereotactic radiotherapy (SRT) are being employed. In our study we aimed to
      describe the various factors affecting outcomes in NSCLC patients receiving local
      therapy for brain metastases. MATERIALS AND METHODS: The case records of 125
      patients with NSCLC and brain metastases consecutively treated with radiotherapy
      at two tertiary centres from January 2006 to June 2012 were analysed for patient,
      tumour and treatment-related prognostic factors. Patients receiving SRS/SRT were
      treated using Cyberknife. Variables were examined in univariate and multivariate
      testing. RESULTS: Overall median survival was 3.4 months (95%CI: 1.7-5.1). Median
      survival for patients with multiple metastases receiving WBRT was 1.5 months, 1-3
      metastases receiving WBRT was 3.6 months and 1-3 metastases receiving surgery or
      SRS/SRT was 8.9 months. ECOG score (<=2 vs >2, p=0.001), presence of seizure (yes
      versus no, p=0.031), treatment modality according to number of brain metastases
      (1-3 metastases+surgery or SRS/SRT+/-WBRT vs 1-3 metastases+WBRT only vs multiple
      metastases+WBRT only, p=0.007) and the use of post-therapy systemic treatment
      (yes versus no, p=0.001) emerged as significant on univariate analysis. All four
      factors remained statistically significant on multivariate analysis. CONCLUSIONS:
      ECOG <=2, presence of seizures, oligometastatic disease treated with aggressive
      local therapy (surgery or SRS/SRT) and the use of post-therapy systemic treatment
      are favourable prognostic factors in NSCLC patients with brain metastases.

PMID- 25773843
TI  - Evaluation of several screening approaches for detection of cervical lesions in
      rural Shandong, China.
AB  - PURPOSE: The study was designed to: (1) investigate the prevalence of high-risk
      human papillomavirus (HR- HPV) infection and cervical neoplasia; and (2) evaluate
      clinical performance of visual inspection with acetic acid/ Lugol's iodine (VIA
      /VILI), Pap smear, high-risk human papillomavirus (HR-HPV) DNA test for detecting
      cervical intraepithelial neoplasia grade 2 or worse (CIN2+) and (3) explore
      appropriate screening approach in rural areas of Shandong Province. MATERIALS AND
      METHODS: A total of 3,763 eligible women from Yiyuan County in Yimeng mountainous
      areas of rural Shandong, China, were enrolled and underwent Pap smear, HR-HPV DNA
      testing by Hybrid Capture 2 (HC2), and VIA /VILI tests. Women positive in any
      test were referred to colposcopy and biopsy as indicated. RESULTS: The prevalence
      of HR-HPV infection among all enrolled women was 11.1% and that in healthy women
      was 9.9%. In total 33 cases of CIN1, 16 cases of CIN2, 6 cases of CIN3 but none
      of cervical cancer were detected and the crude prevalence of CIN2+ was 0.58%. For
      detecting CIN2+, the sensitivity of HR-HPV DNA testing, VIA/VILI, Pap smear was
      90.9%, 77.3%, 81.8%, respectively. Pap smear had the best specificity of 98.2%,
      followed by HR-HPV DNA testing with specificity of 89.4%, VIA/VILI had the lowest
      specificity of 81.2%. Colposcopy referral rate of HR-HPV DNA testing, VIA/VILI,
      Pap smear was 11.1%, 18.5%, 2.3%, respectively. CONCLUSIONS: Our results suggest
      that HR-HPV DNA testing alone might be appropriate for primary cervical cancer
      screening in rural low-resource areas of Shandong Province, China.

PMID- 25773844
TI  - Dietary and demographical risk factors for oesophageal squamous cell carcinoma in
      the Eastern Anatolian region of Turkey where upper gastrointestinal cancers are
      endemic.
AB  - BACKGROUND: Oesophageal squamous cell carcinoma (ESCC) is endemic in the Eastern
      Anatolian region of Turkey. The present study was performed to identify risk
      factors for ESCC that specifically reflect the demography and nutritional habits
      of individuals living in this region. MATERIALS AND METHODS: The following
      parameters were compared in 208 ESCC patients and 200 control individuals in the
      Eastern Anatolian region: age, sex, place of living, socioeconomic level,
      education level, smoking, alcohol intake, nutritional habits, and food
      preservation methods. RESULTS: The mean age of ESCC patients was 56.2 years, and
      87 (41.8%) were 65 years-old or older. The ratio of women to men in the patient
      group was 1.39/1. ESCC patients consumed significantly less fruit and yellow or
      green vegetables and more hot black tea, 'boiled yellow butter', and mouldy
      cheese than did control individuals. Residence in rural areas, smoking, and
      cooking food by burning animal manure were also significantly associated with
      ESCC. CONCLUSIONS: The consumption of boiled yellow butter and mouldy cheese,
      which are specific to the Eastern Anatolian region, and the use of animal manure
      for food preparation were identified as risk factors in this region. Further
      studies are required to potentially identify the carcinogenic substances that
      promote the development of ESCC in this region.

PMID- 25773845
TI  - Evaluation of the frequency of the IL-28 polymorphism (rs8099917) in patients
      with chronic hepatitis C using Zip nucleic acid probes, Kerman, Southeast of
      Iran.
AB  - Polymorphisms in the region of the interleukin IL-28 gene on chromosome 19 have
      been related with clearance of hepatitis C virus (HCV), a major human pathogen
      responsible for chronic hepatitis, cirrhosis and hepatocellular carcinoma. About
      3% of the world's population is infected with HCV. The long-term response to
      therapy is influenced by many host and viral factors, and recent evidence has
      indicated that some host genetic polymorphisms related to IL-28 are the most
      powerful predictors of virological response in patients with HCV. This study
      assessed frequency of the IL-28 polymorphism (rs8099917) in 50 patients (39 men
      and 11 women ) with chronic hepatitis C using ZNA probe real time PCR new method
      . All patients were tested for genotype of HCV and the HCV viral load. In
      parallel, the levels of SGOT, SGPT and ALK enzymes were assessed. Treatment using
      Peg-interferon alpha with ribavirin was conducted for patients and subsequently
      samples were collected to detect any change in viral load or liver enzyme rates.
      The overall frequency of the TT allele is 74%, TG allele 20% and GG allele 6% and
      the percent of patients who had T allele was 84%. Clear reduction in viral load
      and liver enzymes was reported in patients with the T allele. Especially for
      genotype 1 which is relatively resistant to treatment, these alleles may have a
      role in this decline. In conclusion, we showed that IL-28 polymorphism rs8099917
      strongly predicts virological response in HCV infection and that real-time PCR
      with Zip nucleic acid probes is a sensitive, specific and rapid detection method
      for detection of SNPs which will be essential for monitoring patients undergoing
      antiviral therapy.

PMID- 25773846
TI  - CT findings of persistent pure ground glass opacity: can we predict the
      invasiveness?
AB  - BACKGROUND: To investigate whether CT findings can predict the invasiveness of
      persistent cancerous pure ground glass opacity (pGGO) by correlating the CT
      imaging features of persistent pGGO with pathological changes. MATERIALS AND
      METHODS: Ninety five patients with persistent pGGOs were included. Three
      radiologists evaluated the morphologic features of these pGGOs at high resolution
      CT (HRCT). Binary logistic regression was used to assess the association between
      CT findings and histopathological classification (pre-invasive and invasive
      groups). Receiver operating characteristic (ROC) curve analysis was performed to
      evaluate the diagnostic performance of diameters. RESULTS: A total of 105 pGGOs
      were identified. Between pre-invasive (atypical adenomatous hyperplasia, AAH, and
      adenocarcinoma in situ, AIS) and invasive group (minimally invasive
      adenocarcinoma, MIA and invasive lung adenocarcinomas, ILA), there were
      significant differences in diameter, spiculation and vessel dilatation (p<0.05).
      No difference was found in air-bronchogram, bubble- lucency, lobulated-margin,
      pleural indentation or vascular convergence (p>0.05). The optimal threshold value
      of the diameters to predict the invasiveness of pGGO was 12.50mm. CONCLUSIONS:
      HRCT features can predict the invasiveness of persistent pGGO. The pGGO with a
      diameter more than 12.50mm, presences of spiculation and vessel dilatation are
      important factors to differentiate invasive adenocarcinoma from pre-invasive
      cancerous lesions.

PMID- 25773847
TI  - Diagnostic yield of primary circulating tumor cells in women suspected of breast
      cancer: the BEST (Breast Early Screening Test) study.
AB  - PURPOSE: To determine the diagnostic yield of primary circulating tumor cells in
      women with suspicion of breast cancer, detected as a result of an abnormal
      mammography. MATERIALS AND METHODS: Consecutive women presenting for breast
      biopsy as a result of a mammogram BiRADs of 3 or more, had an 8 ml blood sample
      taken for primary circulating tumor cell (CTC) detection. Mononuclear cells were
      obtained using differential gel centrifugation and CTCs identified using standard
      immunocytochemistry using anti-mammoglobin. A test was determined to be positive
      if 1 CTC was detected. RESULTS: A total of 144 women with a mean age of 54.7 +/-
      15.6 years participated, 78/144 (53.0%) had breast cancer on biopsy, 65/140
      (46.3%) benign pathologies and 1(0.7%) non-Hogkins lymphoma. Increasing BiRADs
      scores were associated with increased cancer detection (p=0.004, RR 1.00, 4.24,
      8.50). CTC mammoglobin positive had a sensitivity of 81.1% and specificity of
      90.9%, with positive and negative predictive values of 90.9% and 81.1%
      respectively. Mammoglobin positive CTCs detected 87% of invasive cancers, while
      poorly differentiated cancers were negative for mammoglobin. Only 50% of in situ
      cancers and none of the intraductal cancers had CTCs detected. Menopausal status
      did not affect the diagnostic yield of the CTC test, which was higher in women
      with BiRADS 4 mammograms. There was a significant trend (p<0.0001 Chi squared for
      trends) in CTC detection frequency from intraductal, in situ and invasive (OR
      1.00, 8.00, 472.00). CONCLUSIONS: The use of primary CTC detection in women
      suspected of breast cancer has potential uses, especially with invasive cancer,
      but it failed to detect intra-ductal cancer and 50% of in situ cancer. There was
      no difference in the diagnostic yield between pre and post menopausal women. To
      confirm its use in reducing biopsies in women with BIRADs 4a mammagrams and in
      the detection of interval invasive breast cancer, larger studies are needed.

PMID- 25773848
TI  - Chloroquine exerts anti-metastatic activities under hypoxic conditions in
      cholangiocarcinoma cells.
AB  - Intra-tumoral hypoxia is an environment that promotes tumor cell migration,
      angiogenesis and epithelial- mesenchymal transition that accounts for a major
      mechanism of metastasis. Chloroquine potentially offers a new therapeutic
      approach with an 'old' drug for effective and safe cancer therapies, as it exerts
      anti-metastatic activity. We investigated the inhibitory effect of chloroquine on
      cholangiocarcinoma (CCA) cell migration under cobalt chloride (CoCl2)-stimulated
      hypoxia. We showed that chloroquine suppressed CCA cell migration under hypoxic
      mimicking conditions on exposure to 100 MUM CoCl2. Moreover, chloroquine
      stabilized the protein level of prolyl hydroxylase domain proteins (PHD-2) but
      reduced the levels of hypoxic responsive proteins such as hypoxia-inducible
      factor (HIF-1alpha) and vascular endothelial growth factor (VEGF). It also
      suppressed epithelial mesenchymal transition (EMT) by increasing the ratio of E
      cadherin to N-cadherin under hypoxic conditions. In conclusion, chloroquine can
      inhibit hypoxia-stimulated metastasis via HIF-1alpha/VEGF/EMT which may serve as
      a useful additional strategy for CCA therapy.

PMID- 25773849
TI  - Importance of PET/CT scan use in planning radiation therapy for lymphoma.
AB  - BACKGROUND: Radiation therapy is a key part of the combined modality treatment
      for Hodgkin's lymphoma (HL) and non-Hodgkin's lymphoma (NHL), which can achieve
      locoregional control of disease. The 3D-conformal radiation oncology can be
      extended-field (EFRT), involved-field (IFRT) and involved node (INRT). New
      techniques have resulted in a smaller radiation field and lower dose for critical
      organs such as lung heart and breast. MATERIALS AND METHODS: In our research, we
      made a virtual simulation for one patient who was treated in four different
      radiotherapeutic techniques: mantle field (MFRT), EFRT, IFRT and INRT. After
      delineatiion we compared dose-volume histograms for each technique. The fusion of
      CT for planning radiotherapy with the initial PET/CT was made using Softver Xio
      4.6 in the Focal program. The dose for all four techniques was 36Gy. RESULTS: Our
      results support the use of PET/CT in radiation therapy planning. With IFRT and
      INRT, the burden on the organs at risk is less than with MFRT and EFRT. On the
      other hand, the dose distribution in the target volume is much better with the
      latter. CONCLUSIONS: The aim of modern radiotherapy of HL and NHL is to reduce
      the intensity of treatment and therefore PET/CT should be used to reduce and not
      increase the amount of tissue receiving radiation.

PMID- 25773850
TI  - Treatment outcomes and survival study of gastric cancer patients: a retrospective
      analysis in an endemic region.
AB  - PURPOSE: To present information about prognostic factors of gastric cancer
      patients treated in our Erzurum center including age, gender, tumour location,
      pathological grade, stage and the effect of treatment on survival. MATERIALS AND
      METHODS: This retrospective study was performed on patients who applied to our
      clinic and diagnosed as gastric cancer. Age and gender of the patients, primary
      location, histopathological characteristics, TNM stage of the gastric cancers
      (GCs), treatment applied, oncological treatment modalities and survival outcomes
      were studied. A univariate analysis of potential prognostic factors was performed
      with the log-rank test for categorical factors and parameters with a p value <
      0.05 at the univariate step were included in the multivariate regression.
      RESULTS: A total of 228 patients with a confirmed diagnosis of gastric cancer
      were included in the study with a male/female ratio of 1.47. Median follow-up
      period was estimated as 22.3 (range, 3 to 96) months. When diagnosis of the
      patients at admission was analysed, stage III patients were most frequently
      encountered (n=147; 64.5%). One hundred and twenty-six (55.3%) underwent surgical
      treatment, while 117 (51.3%) were given adjuvant chemotherapy. Median overall
      survival time was 18.0 (+/- 1.19) months. Mean overall survival rates for 1, 2, 3
      and 5 years were 68 +/- 0.031%, 36 +/- 0.033%, 24 +/- 0.031% and 15.5 +/- 0.036%,
      respectively. Univariate variables found to be significant for median OS in the
      multivariate analysis were evaluated with Cox regression analysis. A significant
      difference was found among TNM stage groups, location of the tumour and
      postoperative adjuvant treatment receivers (p values were 0.011, 0.025 and 0.001,
      respectively). CONCLUSIONS: This study revealed that it is possible to achieve
      long-term survival of gastric cancer with early diagnosis. Besides, in locally
      advanced GC patients, curative resection followed by adjuvant concomitant
      chemoradiotherapy based on the McDonald regimen was an independent prognostic
      factor for survival.

PMID- 25773851
TI  - Growth of human colon cancer cells in nude mice is delayed by ketogenic diet with
      or without omega-3 fatty acids and medium-chain triglycerides.
AB  - BACKGROUND: Tumors are largely unable to metabolize ketone bodies for energy due
      to various deficiencies in one or both of the key mitochondrial enzymes, which
      may provide a rationale for therapeutic strategies that inhibit tumor growth by
      administration of a ketogenic diet with average protein but low in carbohydrates
      and high in fat. MATERIALS AND METHODS: Thirty-six male BALB/C nude mice were
      injected subcutaneously with tumor cells of the colon cancer cell line HCT116.
      The animals were then randomly split into three feeding groups and fed either a
      ketogenic diet rich in omega-3 fatty acids and MCT (MKD group; n=12) or lard only
      (LKD group; n=12) or a standard diet (SD group; n=12) ad libitum. Experiments
      were ended upon attainment of the target tumor volume of 600 mm3 to 700 mm3. The
      three diets were compared for tumor growth and survival time (interval between
      tumor cell injection and attainment of target tumor volume). RESULTS: The tumor
      growth in the MKD and LKD groups was significantly delayed compared to that in
      the SD group. CONCLUSIONS: Application of an unrestricted ketogenic diet delayed
      tumor growth in a mouse xenograft model. Further studies are needed to address
      the mechanism of this diet intervention and the impact on other tumor-relevant
      parameters such as invasion and metastasis.

PMID- 25773852
TI  - Changing trends of adult lymphoma in the Kingdom of Saudi Arabia - comparison of
      data sources.
AB  - BACKGROUND: Lymphoma is one of the most common malignancies affecting the young
      Saudi population. This disease has diversified pathologies and clinical stages
      that necessitate well optimized clinical management. Regular updates of
      epidemiological behavior of lymphoma from various parts of the world are
      available but studies from the Kingdom of Saudi Arabia (KSA) in this field are
      not consistent. OBJECTIVES: The aim of this study was to investigate the current
      trends in presentation and distribution of lymphoma with special reference to
      incidence and mortality, gender, age, histopathological subtypes, and clinical
      stages at King Faisal Specialist Hospital and Research Centre (KFSH and RC).
      MATERIALS AND METHODS: Our study included lymphoma data from Saudi Cancer
      Registry, and relative comparison against KFSH and RC tumor registry data, Gulf
      country data and International Agency for Research on Cancer data. RESULTS:
      Common tumors in the West (lung, colon, and prostate) were found to be much less
      frequent in KSA while leukemia, lymphoma and thyroid cancers were more common.
      Non-Hodgkin Lymphoma (NHL) ranked 3rd most common cancer with age-adjusted
      incidence of 6/100,000. Estimated age adjusted mortality was 4/100,000 in KSA.
      There was a peak rise in incidence of lymphoma in 1997-2007. Most common NHL was
      diffuse large B cell lymphoma at KFSH and RC. A total of 434 cases were diagnosed
      in 5 years with 55% of them at advanced stage and 35% demonstrating bulky disease
      and high risk. KFSH and RC registered 35% of Hodgkins and 21% of total NHL
      identified in entire Saudi Cancer Registry, 2009. CONCLUSIONS: Results of this
      study are very unique, and reveal diverse trends. The findings provide valuable
      insights in the understanding of current epidemiological features of lymphoma in
      this part of the world.

PMID- 25773853
TI  - Prevalence of human papillomavirus types and phylogenetic analysis of HPV-16 L1
      variants from Southern India.
AB  - BACKGROUND: The human papillomavirus (HPV) and its variants show wide
      geographical distribution and have been reported to cause cervical lesions. With
      cervical neoplasia as the leading cancer in Indian women, the aim of the present
      study was to evaluate the multiple infection HPV type distribution and variant
      genotypes in cervical samples from the coastal Karnataka region, India. MATERIALS
      AND METHODS: A total of 212 samples were screened by nested polymerase chain
      reaction using PGMY9/11 and GP5+/6+ primers. HPV positive samples were sequenced
      to identify the types and a phylogenetic tree was constructed using the neighbor
      joining method. RESULTS: Sequence analysis identified a total of 14 HPV types
      distributed in 20%, 73.3% and 82.5% of non-malignant, pre-malignant [low grade
      squamous intraepithelial lesion (LSIL) and high grade squamous intraepithelial
      lesion (HSIL)] and cervical cancer samples. The distribution of high risk HPV in
      cancer samples was HPV 16, 76.4%, HPV18, 11.7%, HPV81, 2.9%, HPV31, 1.4%, HPV35,
      1.4% and HPV 45, 1.4%. Multiple infections were observed in 11.8% of tumor
      samples with HPV 16 contributing to 62.5% of cases. In non-malignant samples, 20%
      of HPV positive samples were detected with HPV16, 82.3%, HPV33, 5.8% and HPV58,
      5.8% and very low incidence of multiple infections. Comparative phylogenetic
      analysis of HPV variants identified 9 HPV sequences as new papillomavirus
      species, predominantly classified as European lineage type. CONCLUSIONS: The
      findings for HPV infections associated with progression of cervical cancer in
      coastal Karnataka region and HPV variant analysis provide baseline data for
      prevention and HPV vaccination programs.

PMID- 25773854
TI  - Anti-angiogenic activity of gecko aqueous extracts and its macromolecular
      components in CAM and HUVE-12 cells.
AB  - Gecko is a kind of traditional Chinese medicine with remarkable antineoplastic
      activity. However, undefined mechanisms and ambiguity regarding active
      ingredients limit new drug development from gecko. This study was conducted to
      assess anti-angiogenic properties of the aqueous extracts of fresh gecko (AG) or
      macromolecular components separated from AG (M-AG). An enzyme-linked
      immunosorbent assay (ELISA) approach was applied to detect the vascular
      endothelial growth factor (VEGF) secretion of the tumor cells treated with AG or
      M-AG. The effect of AG or M-AG on vascular endothelial cell proliferation and
      migratory ability was analyzed by tetrazolium dye colorimetric method, transwell
      and wound-healing assays. Chick embryo chorioallantoic membrane (CAM) assays were
      used to ensure the anti-angiogenic activity of M-AG in vivo. The results showed
      that AG or M-AG inhibited the VEGF secretion of tumor cells, the relative
      inhibition rates of AG and M-AG being 27.2% and 53.2% respectively at a
      concentration of 20 MUL/mL. AG and M-AG inhibited the vascular endothelial (VE)
      cell proliferation with IC50 values of 11.5 +/- 0.5 MUL/mL and 12.9 +/- 0.4
      MUL/mL respectively. The VE cell migration potential was inhibited significantly
      (p<0.01) by the AG (>= 24 MUL/mL) or M-AG (>= 12 MUL/ mL) treatment. In vivo,
      neovascularization of CAM treated with M-AG was inhibited significantly (p<0.05)
      at a concentration of 0.4 MUL/mL. This study provided evidence that anti
      angiogenesis is one of the anti-tumor mechanisms of AG and M-AG, with the latter
      as a promising active component.

PMID- 25773855
TI  - Silibilin-induces apoptosis in breast cancer cells by modulating p53, p21, Bak
      and Bcl-XL pathways.
AB  - Nowadays herbal-derived medicines are attracting attention as new sources of
      drugs with few side effects. Silibinin is a flavonoid compound with
      chemotheraputic effects on different cancers such as examples in the prostate,
      lung, colon and breast. In the present study, the cytotoxic effects of silibinin
      on MCF7 breast cancer cells were investigated. Apoptosis was determined by flow
      cytometry and the impact of silibinin on the expression of pivotal genes
      including Bak, P53, P21, BRCA1, BCL-X1 and ATM was analyzed. Treatment for 24h
      had a significant dose-dependent inhibitory effect on cell growth (p<0.05) with
      dose- and time- dependent induction of apoptosis (p<0.05). In addition, there
      were significant increases in BRCA1, ATM, Bak and Bcl-XL gene expression at the
      mRNA level with different concentrations of silibinin for 24 or 48 h (p<0.05).
      Taken together, the results suggest that silibinin inhibits the proliferation and
      induces apoptosis of MCF-7 cells by down-regulating Bak, P53, P21, BRCA1, BCL-Xl
      and thus may be considered as an effective adjuvant drug to produce a better
      chemopreventive response for the cancer therapy.

PMID- 25773856
TI  - Once-weekly subcutaneous administration of bortezomib in patients with multiple
      myeloma.
AB  - In patients with multiple myeloma (MM), once-weekly intravenous injection or
      twice-weekly subcutaneous injection (SC) of bortezomib has been proven to offer
      non-inferior efficacy to standard twice-weekly intravenous administration, with
      an improved safety profile. However, whether once-weekly SC bortezomib can
      further reduce the incidence rate of peripheral neuropathy (PN) and not
      compromise the efficacy remains to be investigated. 25 patients of MM treated
      with once-weekly SC bortezomib were reviewed in this study. The median treatment
      cycles were 4 (range, 2-9 cycles). Complete response (CR) rate was 52%, >=very
      good partial response (VGPR) rate was 72%, and >=partial response (PR) rate was
      84%. 1-year and 2-year PFS rate was 63.0% and 34.3%, respectively, and 2-year OS
      rate was 100%. Any grade of PN was reported in 9 patients (36.0%), with 7
      patients (28.0%) had grade 1 PN, and 2 patients (8.0%) had grade 2 PN. No
      patients reported grade 3/4 PN in this cohort. In conclusion, once-weekly
      subcutaneous administration of bortezomib offers excellent efficacy with a
      further improved safety profile, especially with regard to PN. It needs to be
      validated in future prospective randomized trials.

PMID- 25773857
TI  - Expression of Laminingamma2 in extrahepatic cholangiocarcinoma tissues and its
      influence on tumor invasion and metastasis.
AB  - OBJECTIVE: To explore the expression of laminingamma2 in extrahepatic
      cholangiocarcinoma (EHCC) tissues and its influence on tumor invasion and
      metastasis. MATERIALS AND METHODS: Paraffin embedding samples of cancer, para
      cancer, lymph node metastatic and hepatic metastatic tissues from 79 patients
      undergoing EHCC resection were collected. Expression of laminingamma2 was
      detected by immunohistochemistry and its relationship with clinical pathological
      characteristics and the prognosis of EHCC patients were analyzed. RESULTS:
      Laminingamma2 showed negative staining in para-cancer tissues, but demonstrated a
      51.9% (41/79) positive expression rate in extracellular matrix (ECM) or cytoplasm
      of EHCC tissues. In lymph node metastatic and distant metastatic nidi, expression
      of laminingamma2 was significantly higher than in the primary nidi (chi2=7.4173,
      P=0.0065; chi2=4.0077, P=0.0453). The expression was in obvious association with
      lymph node metastasis (P<0.01), but had no relevance with age, gender, tumor
      location, tumor stage, differentiation and distant metastasis in ECM (P>0.05),
      whereas it was in marked connection with lymph node and distant metastasis
      (P<0.05 or P<0.01), but had no relationship with age, gender, tumor location,
      tumor stage and differentiation in cytoplasm (P>0.05). However, the median
      survival time and median recurrent period of patients with positive expression of
      laminingamma2 in both cytoplasm and ECM of tumor cells, only in ECM and only in
      cytoplasm, were evidently lower than with negative expression of laminingamma2 in
      RCM and cytoplasm (P<0.05 or P<0.01). Further Cox regression analysis showed that
      the positive expression of laminingamma2 and the tumor differentiation were
      independent risk factors influencing the prognosis of EHCC patients. CONCLUSIONS:
      Abnormal expression of laminingamma2 may be closely associated with invasion and
      metastasis of tumor cells, and thus a potential molecular marker for prognosis of
      EHCC patients.

PMID- 25773858
TI  - Denosumab - a monoclonal antibody, not a radionuclide.

PMID- 25773859
TI  - Careful diagnosis of aortic invasion in patients with lung cancer using modern
      diagnostic imaging.

PMID- 25773860
TI  - The density of microvessels positive for Wilms' tumour-1 protein (WT-1) is an
      independent predictor of recurrence risk in meningiomas.
AB  - Wilms' tumour-1 (WT-1) protein m-RNA was recently demonstrated in meningiomas,
      suggesting the potential application of WT-1 immunotherapy in these tumours. The
      aim of the present study was to analyze the immunohistochemical expression of WT
      1 protein, its correlation with the clinico-pathological variables and
      association with vascular endothelial growth factor (VEGF) expression, in a
      series of 60 meningiomas of different histotype and histological grade. None of
      the cases expressed WT-1 in the neoplastic cells, while endothelial expression
      was evidenced in a variable number of tumour vessels in all the meningiomas. The
      density of microvessels positive for WT-1 (WT-1 MVD) was significantly higher in
      meningiomas showing higher histological grade (P = 0.0191), growth fraction (P =
      0.0201), expression of VEGF (P = 0.0288) and recurrence risk (P = 0.022). In
      addition, high WT-1 MVD was a significant independent predictive factor for a
      shorter recurrence-free survival (RFS) in patients with completely resected
      meningiomas (P = 0.0028). In conclusion, this study shows that WT-1 MVD is
      correlated with the biological aggressiveness of meningiomas. Although no
      staining for WT-1 was evidenced in the neoplastic cells of these tumours, WT-1
      endothelial expression in the tumour vessels might represent a target for WT-1
      immunotherapy in the aim of reducing their blood supply and growth.

PMID- 25773861
TI  - Cord blood n-3 LC-PUFA is associated with adiponectin concentrations at 10 years
      of age.
AB  - An elevated ratio of n-6 to n-3 long-chain (LC-) polyunsaturated fatty acids
      (PUFA) may be a potential risk factor for obesity development. N-3 LC-PUFA are
      thought to alter adiponectin concentrations, and thus may have a beneficial
      effect on weight development. We analysed the association between n-3 LC-PUFA
      concentrations in cord blood and adiponectin concentrations at 10 years. Fatty
      acid composition was measured in cord blood and at 10 years of age by gas
      chromatography, and adiponectin concentrations were measured only at 10 years of
      age in 237 children from the Munich LISAplus birth cohort study. Linear
      regression models assessed associations between n-3 LC-PUFA, n-6 LC-PUFA and the
      n-6/n-3 ratio in cord blood with adiponectin concentrations at 10 years of age.
      LC-PUFA were presented as percentages and categorized into tertiles. Regression
      models were adjusted for LC-PUFA percentages at 10 years of age and other
      potential confounding factors. Cord blood n-3 LC-PUFA tertiles were significantly
      associated with adiponectin concentrations in an inverse J-shaped relationship
      [2nd tertile versus 1st tertile: Beta=1.84 (SE=0.65), and 3rd tertile versus 1st
      tertile: 1.02 (0.68), p-value<0.01 (ANOVA)]. Further, cord blood n-6/n-3 ratios
      were significantly associated with adiponectin concentrations [2nd tertile versus
      1st tertile: 0.14 (0.67), and 3rd tertile versus 1st tertile: -1.37 (0.68), p
      value=0.03 (ANOVA)]. The cord blood n-6 LC-PUFA tertiles were not associated with
      adiponectin concentrations. Our results suggest that a higher n-3 LC-PUFA
      concentrations and a lower n-6/n-3 ratio in cord blood are associated with higher
      adiponectin concentrations at 10 years of age. 

PMID- 25773862
TI  - Evaluation of electronic prescription implications in Turkey: an investigation of
      the perceptions of physicians.
AB  - BACKGROUND: Electronic prescribing (e-prescribing) is an evolving area of
      healthcare information technology that aims to support physician decision-making
      by capturing, reviewing, and issuing medical prescriptions with high potential
      for improving the quality and safety of the process. PURPOSE: To describe
      physician perception of e-prescription use in healthcare organizations that work
      with social security and to evaluate their infrastructures for MEDULA (an
      information system for billing and other health informatics) in healthcare
      organizations in Turkey. METHODS: A cross-sectional survey design was used for
      this study. A convenience sample of physicians in eight general hospitals and in
      two oral and dental health centers of the Ministry of Health in Turkey were
      surveyed. RESULTS: Survey response rate was 47% (248/425). The majority of
      physicians (62%) support e-prescribing but have not used an electronic signature
      for prescriptions (78.2%). Almost half of them believe that e-prescriptions would
      positively contribute to patient safety (43%) LINKING EVIDENCE TO ACTION: Our
      study provides a first look at the perceptions of physicians regarding the
      implications of e-prescriptions, which became mandatory on January 15, 2013, in
      Turkey. Advocates of e-prescribing have suggested that additional efforts are
      needed to strengthen clinical decision systems. Physicians and nurses are better
      able to adopt e-prescribing systems and to view them positively if they recognize
      the limitations of paper-based prescribing and understand the utility of
      electronic systems in addressing some of these limitations. This study represents
      a starting point for government and related organizations to improve their
      knowledge on how well the implied benefits of e-prescriptions are realized in
      their acquisition, appraisal, and use in health policy decision-making and health
      systems.

PMID- 25773863
TI  - Dopamine signals and physiological origin of cognitive dysfunction in Parkinson's
      disease.
AB  - The pathological hallmark of Parkinson's disease (PD) is the degeneration of
      midbrain dopamine neurons. Cognitive dysfunction is a feature of PD patients even
      at the early stages of the disease. Electrophysiological studies on dopamine
      neurons in awake animals provide contradictory accounts of the role of dopamine.
      These studies have established that dopamine neurons convey a unique signal
      associated with rewards rather than cognitive functions. Emphasizing their role
      in reward processing leads to difficulty in developing hypothesis as to how
      cognitive impairments in PD are associated with the degeneration of dopamine
      circuitry. A hint to resolve this contradiction came from recent
      electrophysiological studies reporting that dopamine neurons transmit more
      diverse signals than previously thought. These studies suggest that dopamine
      neurons are divided into at least two functional subgroups, one signaling
      "motivational value" and the other signaling "salience." The former subgroup fits
      well with the conventional reward theory, whereas the latter subgroup has been
      shown to transmit signals related to salient but non-rewarding experiences such
      as aversive stimulations and cognitively demanding situations. This article
      reviews recent advances in understanding the non-reward functions of dopamine,
      and then discusses the possibility that cognitive dysfunction in PD is at least
      partially caused by the degeneration of the dopamine neuron subgroup signaling
      the salience of events in the environment.

PMID- 25773864
TI  - 1,4,8,11,15,18,22,25-Alkylsulfanyl phthalocyanines: effect of macrocycle
      distortion on spectroscopic and packing properties.
AB  - The effect of phthalocyanine macrocycle distortion on its spectroscopic and
      packing properties is studied, by comparing two phthalocyanines octa-non
      peripherally substituted by alkanethiols of different bulkiness (n-hexyl and tert
      butyl). Their X-ray structures evidence their core shape, respectively planar and
      strongly distorted, inducing a 55 nm shift of their maximum absorption
      wavelength. Comparison of frontier orbital energies revealed that this distortion
      decreases the conjugation potency of the benzo rings to the central pyrrolic
      rings. Also the tert-butyl derivative presents a MOF-like porous crystalline
      assembly with 22.2% void. 

PMID- 25773865
TI  - Determination of the pseudoephedrine content in pharmaceutical formulations and
      in biological fluids using a microbore HPLC system interfaced to a microfluidic
      chemiluminescence detector.
AB  - A novel automated precolumn derivatization followed by separation using liquid
      chromatography for the determination of pseudoephedrine (PSE) by a microfluidic
      chemiluminescence detector has been developed. An on-line derivatization
      procedure was utilized by converting PSE into a highly light emitting species in
      a Ru(bipy)3(2+)-peroxydisulphate chemiluminescence (CL) system by derivatizing it
      with a 1.0 M formaldehyde solution. The derivatized analyte was directly injected
      into a microbore high-performance liquid chromatography (HPLC) system coupled to
      an on-chip chemiluminescence detector. The newly developed highly selective,
      sensitive and fast HPLC-CL method was validated and successfully applied for the
      analysis of PSE in pharmaceutical formulations and a human urine sample. The
      selectivity of the method is not only due to the HPLC separation but is also due
      to the highly selective detection principle of the Ru(bipy)3(2+)-peroxydisulphate
      CL system used. There was no interference observed from the common preservatives
      and excipients used in pharmaceutical preparations, which did not show any
      significant CL signal. The retention time of PSE was less than 3 min, and the
      detection limits and quantification limits were found to be 5.7 and 26.0 ug L(
      1), respectively.

PMID- 25773866
TI  - Clinical and prognostic implications of RET rearrangements in metastatic lung
      adenocarcinoma patients with malignant pleural effusion.
AB  - OBJECTIVES: RET rearrangements represent one of the newest molecular targets in
      non-small cell lung cancer (NSCLC). However, the prevalence, clinical
      characteristics, and outcome of patients with RET-rearranged lung adenocarcinoma
      in metastatic disease remain uncertain. MATERIALS AND METHODS: Multiplex reverse
      transcription-polymerase chain reaction (RT-PCR) was used to detect KIF5B-RET and
      CCDC6-RET fusions from specimens of malignant pleural effusion (MPE) in patients
      with metastatic lung adenocarcinoma. The demographic data and outcome of patients
      with RET-rearranged tumors were compared with those with EGFR-mutant, KRAS
      mutant, EML4-ALK-rearranged, and quadri-negative tumors. RESULTS: Of the 722
      patients with MPE of lung adenocarcinoma screened, 17 (2.4%) had RET-rearranged
      tumors. The detected RET rearrangements comprised 11 (65%) KIF5B-RET and 6 (35%)
      CCDC6-RET fusions, including 2 novel fusion variants identified. The presence of
      RET rearrangements was not associated with age at diagnosis, gender or smoking
      history, but predominantly seen in solid histological subtype. None of patients
      with RET-rearranged tumors had received kinase inhibitors with activity against
      RET kinase. The median overall survival was 22.4 months (95% CI, 8.8-36.0) for
      the 17 patients with RET-rearranged tumors, compared with 21.3 months (95% CI,
      18.7-23.9; P=0.57) for the 451 patients with EGFR-mutant tumors, 5.4 months (95%
      CI, 2.7-8.1; P=0.002) for the 13 patients with KRAS-mutant tumors, 18.9 months
      (95% CI, 10.7-27.1; P=0.82) for the 51 patients with EML4-ALK-rearranged tumors,
      and 12.0 months (95% CI, 9.0-15.0; P=0.07) for the 190 patients with quadri
      negative tumors. CONCLUSION: Multiplex RT-PCR from specimens of MPE is feasible
      for the screening of RET rearrangements in NSCLC. Metastatic RET-rearranged lung
      adenocarcinoma patients with MPE might have favorable survival comparable to
      those with metastatic EGFR-mutant tumors.

PMID- 25773867
TI  - Twelve-Month Prevalence of DSM-5 Gambling Disorder and Associated Gambling
      Behaviors Among Those Receiving Methadone Maintenance.
AB  - This study sought to: (1) determine the prevalence of gambling disorder using the
      Diagnostic and Statistical Manual of Mental Disorders Version 5 (DSM-5; American
      Psychiatric Association in Diagnostic and statistical manual of mental disorders,
      American Psychiatric Publishing, Arlington, 2013) criteria; (2) identify the
      frequency and amount of money spent on gambling behaviors; and (3) determine
      demographic and treatment related predictors associated with gambling disorder in
      a substance using population. People receiving methadone maintenance treatment (N
      = 185) in an urban medical center consented to participate in the study. We used
      DSM-5 criteria to assess the 12-month prevalence of gambling disorder. Questions
      adapted from a previously developed measure were used to identify, describe and
      quantify the frequency of use and amount of money spent on gambling behaviors.
      Most participants were African-American (71.4 %), male (54.1 %), unmarried (76.8
      %), unemployed (88.1 %) and had an income of <$20,000 (88.5 %). On average,
      participants were receiving 81.0 mg of methadone (SD: 22.8) daily. Nearly half
      (46.2 %) of participants met DSM-5 criteria for gambling disorder. Compared to
      those without gambling disorder, those with gambling disorder did not differ
      significantly with respect to demographic characteristics nor methadone dose.
      However, those with gambling disorder had been in methadone maintenance treatment
      for significantly less time. Those with gambling disorder were significantly more
      likely to report engaging in a variety of gambling behaviors. Given that the 12
      month prevalence of DSM-5 defined gambling disorder was nearly 50 % future
      efforts to screen and treat gambling disorder in the context of methadone
      maintenance treatment are clearly warranted. 

PMID- 25773868
TI  - Sociodemographic Correlates and Morbidity in Lottery Gamblers: Results from a
      Population Survey.
AB  - The aim of the current study was to examine the socio-demographic correlates, the
      association of mental and physical illness, and the prevalence of pathological
      gambling among three groups (1) those with lottery gambling only (2) those with
      lottery and other types of gambling and (3) those with other types of gambling
      only-such as playing cards, sports betting, horse racing, casino gambling etc.
      Data was used from a nationwide cross-sectional epidemiological nationally
      representative survey of the resident (Singapore Citizens and Permanent
      Residents) population in Singapore of 6616 Singaporean adults aged 18 years and
      older. All respondents were administered the South Oaks Gambling Screen to screen
      for pathological gambling. The diagnoses of mental disorders were established
      using the Composite International Diagnostic Interview and relevant socio
      demographic data was collected using a structured questionnaire. Lottery gambling
      was by far the most popular form of gambling in Singapore, with 83.5 % of those
      who had ever gambled indicating that they had participated in lottery gambling.
      Those who participated in lottery gambling alone were more likely to belong to
      the older age group (as compared to the 18-35 years age group), be of Indian
      ethnicity, have a secondary or vocational education, and earn a lower income as
      compared to the other two groups. Our findings that those with pure lottery
      gambling were significantly less likely to be pathological gamblers and had
      significantly lower odds of psychiatric and physical morbidity as compared to the
      other two groups are unique and need further research. 

PMID- 25773869
TI  - The Gambling Preferences and Behaviors of a Community Sample of Australian
      Regular Video Game Players.
AB  - Research has noted many similarities between video gaming and gambling
      activities. It has been suggested that video game players may also be attracted
      to gambling, although there is limited research on this possibility. The present
      study examined concurrent video gaming and gambling habits in a sample of regular
      video game players in Australia (N = 485, 84 % male, M age = 25.8). Gambling
      involvement was found to be a generally unpopular activity among regular video
      game players. No significant association between frequency of video game play and
      frequency of gambling was found. Although significant correlations between gaming
      'addiction' scores and gambling frequency were identified, age was the only
      significant predictor of gambling when controlling for all remaining variables.
      These findings are critically discussed in the context of past research, and
      future research directions concerning the link between video gaming and gambling
      are proposed. 

PMID- 25773870
TI  - Problem Gambling Associated with Violent and Criminal Behaviour: A Danish
      Population-Based Survey and Register Study.
AB  - This study compares the number of criminal charges among problem gamblers (N =
      384) and non-problem gamblers including non-gamblers (N = 18,241) and examines
      whether problem gambling is more strongly associated with income-generating
      crimes like theft, fraud and forgery than other types of crimes such as violent
      crimes. A cohort study was carried out, based on data from the Danish Health and
      Morbidity Surveys in 2005 and 2010, which were linked at the individual level
      with data from The Danish National Criminal Register. Multiple logistic
      regression analyses were used to determine the association between problem
      gambling and charges for different categories of crime. We found that problem
      gamblers had significantly higher odds of being charged than non-problem gamblers
      (adjusted odds ratio 1.5; 95 % confidence interval 1.1-1.9). The odds ratio for
      economic crime charges was 2.6 (1.5-4.5), for violence charges 2.2 (1.1-4.5), and
      for drug charges 3.7 (1.7-8.0). For road traffic charges the odds ratio was 1.3
      (1.0-1.8). Hence, there was a strong association between problem gambling and
      being charged except for road traffic charges; however the association was not
      stronger for economic charges than for violence and drug charges. 

PMID- 25773871
TI  - A comparison of the impacts of continuous and interval cycle exercise on
      perceived exertion.
AB  - Ratings of perceived exertion (RPE) were developed to assess exertion during
      exercise testing. However, assessments of RPE prior to and after exercise have
      become common and potentially important in understanding exercise behaviour. The
      purpose of this project was to compare RPE taken before, during and after
      interval and continuous exercise sessions. Twenty-four participants (12 men, 12
      women, body mass index = 24, VO2peak = 41 mL . kg . min(-1)) completed a maximal
      cycle ergometer test used to prescribe experimental trials: (1) moderate
      continuous (MC), (2) vigorous continuous (VC), (3) vigorous interval and (4)
      severe interval. All trials were 20 minutes in length and all intervals utilised
      60-second segments and a 1:1 work-to-rest ratio. Predicted exertion was highest
      in the continuous vigorous trial (p < .05). Exertion increased from beginning to
      end in all trials (p < .05). Session RPE values were highest for the continuous
      vigorous trial (p < .05). Findings suggest that interval protocols produce
      perceptions of effort that are lower than VC exercise but similar to MC exercise.
      These results help describe the perceptions of effort associated with continuous
      and interval exercise and suggest that interval exercise can be performed with
      lower perceived work, which may encourage increased participation.

PMID- 25773872
TI  - Isoquinoline-based Werner clathrates with xylene isomers: aromatic interactions
      vs. molecular flexibility.
AB  - The crystal structures of the Werner clathrates Ni(NCS)2(isoquinoline)4 (H) with
      para-xylene (px), meta-xylene (mx) and ortho-xylene (ox) have been elucidated.
      The kinetics of thermal decomposition of the three inclusion compounds were
      performed using the isothermal technique of Flynn and Wall. Selectivity of H for
      the xylene isomers was determined for both the liquid and vapour phase binary
      mixtures of the xylenes. The chosen ligand has a larger aromatic system to
      improve the possible pi interactions between H and the selected guests. The
      planarity of the isoquinoline ligand causes H rigidity and its selectivity was
      compared to a related Werner complex containing the more flexible 4
      phenylpyridine. 

PMID- 25773874
TI  - Erratum to: The effect of lanthanum(III) and cerium(III) ions between layers of
      manganese oxide on water oxidation.

PMID- 25773875
TI  - Does the year-end decline in injury risk reflect reporting error?
AB  - BACKGROUND: Relatively little is known about seasonal patterns in occupational
      injury risk. Injury risk may vary seasonally due to weather-related factors or
      changing work exposure. Employer confusion about recordkeeping rules and injury
      occurrence near year end may also lead to an undercount of year-end injuries.
      METHODS: Case records from the Bureau of Labor Statistics' Survey of Occupational
      Injuries and Illnesses and Census of Fatal Occupational Injuries were used to
      determine seasonality for a variety of injury types. RESULTS: Reported injury
      rates were higher in summer and lower at year end. Difficult-to-identify injuries
      showed greater year-end incidence declines. CONCLUSIONS: End-of-year injury
      declines may have reflected reporting errors for some injury types. The
      summertime increase in injury risk was broad-based and presumably reflected real
      seasonal factors.

PMID- 25773876
TI  - The Preoperative Lymphocyte-to-Monocyte Ratio is Prognostic of Clinical Outcomes
      for Patients with Liver-Only Colorectal Metastases in the Neoadjuvant Setting.
AB  - BACKGROUND: Circulating monocyte-derived, tumor-associated macrophages are
      associated with a poor prognosis for various cancers. Conversely, circulating
      lymphocytes are the source of tumor-infiltrating lymphocytes, which are
      associated with an improved prognosis. This study evaluated the prognostic value
      of the preoperative blood lymphocyte-to-monocyte ratio (LMR) for patients
      undergoing hepatectomy for liver-only colorectal metastases. METHODS: This
      retrospective study examined 140 consecutive patients with liver-only colorectal
      metastases. Disease-free survival (DFS), post-recurrence survival (PRS), cancer
      specific survival (CSS), and overall survival (OS) were analyzed in relation to
      LMR values using both Kaplan-Meier and multivariate Cox-regression methods.
      RESULTS: In the multivariate analysis, high LMR (>3) was significantly associated
      with increased OS [hazard ratio (HR), 2.43; 95 % confidence interval (CI), 1.32
      4.48; P = 0.004], CSS (HR 2.15; 95 % CI 1.13-4.10; P = 0.020), and PRS (HR 2.15;
      95 % CI 1.15-4.01; P = 0.016) but not with DFS. An LMR lower than 3 may have been
      associated with decreased CSS and PRS by increasing the rate of multifocal
      recurrence (P = 0.063). In the multivariate analysis comparing LMR, the
      neutrophil-lymphocyte ratio, and the platelet-lymphocyte ratio, LMR remained the
      only significant prognostic variable of CSS. CONCLUSION: This study identified
      preoperative LMR as an independent prognostic factor for PRS, CSS, and OS but not
      for DFS in patients undergoing hepatectomy for liver-only colorectal metastases.
      In the future, interventions to augment immune function could improve survival
      for low-LMR patients.

PMID- 25773873
TI  - Light-harvesting regulation from leaf to molecule with the emphasis on rapid
      changes in antenna size.
AB  - In the sunlight-fluctuating environment, plants often encounter both light
      deficiency and light-excess cases. Therefore, regulation of light harvesting is
      absolutely essential for photosynthesis in order to maximize light utilization at
      low light and avoid photodamage of the photosynthetic apparatus at high light.
      Plants have developed a series of strategies of light-harvesting regulation
      during evolution. These strategies include rapid responses such as leaf movement
      and chloroplast movement, state transitions, and reversible dissociation of some
      light-harvesting complex of the photosystem II (LHCIIs) from PSII core complexes,
      and slow acclimation strategies such as changes in the protein abundance of light
      harvesting antenna and modifications of leaf morphology, structure, and
      compositions. This review discusses successively these strategies and focuses on
      the rapid change in antenna size, namely reversible dissociation of some
      peripheral light-harvesting antennas (LHCIIs) from PSII core complex. It is
      involved in protective role and species dependence of the dissociation,
      differences between the dissociation and state transitions, relationship between
      the dissociation and thylakoid protein phosphorylation, and possible mechanism
      for thermal dissipation by the dissociated LHCIIs. 

PMID- 25773877
TI  - Expressional STAT3/STAT5 Ratio is an Independent Prognostic Marker in Colon
      Carcinoma.
AB  - BACKGROUND: Signal transducer and activator of transcription proteins (STATs) are
      crucial regulators of cell growth and differentiation; however, their specific
      prognostic impact in human colon cancer has only been studied to limited extent.
      We aimed to assess the prognostic significance of specific STAT expression
      patterns in colon carcinoma. METHODS: Protein expression patterns of activated
      STAT1, STAT3, STAT4, and STAT5 in human colon carcinoma tissue and corresponding
      healthy mucosa (n = 104) were assessed using multiplex bead-based immunoassay
      technologies. Expression patterns were correlated with clinical and survival
      data. Immunohistochemistry was performed to assess spatial expression of STAT3
      and STAT5. RESULTS: STAT3 was underexpressed whereas STAT4 and STAT5 were
      overexpressed in colon carcinoma tissue. Primary tumors from patients with
      distant metastases (M1) displayed significantly increased expression of STAT1 and
      STAT3 but decreased expression of STAT4 and STAT5. Increased tumor expression of
      STAT1 or STAT3 was associated with impaired patient survival, whereas increased
      expression of STAT4 or STAT5 correlated with improved survival. Multivariate
      analysis identified an increased STAT3/STAT5 expressional ratio as an adverse
      prognostic marker in colon cancer patients. CONCLUSIONS: The tumor progression
      associated transcription factors STAT3, STAT4, and STAT5 are differently
      expressed in colon carcinoma tissue and colon mucosa. Moreover, the STAT3/STAT5
      expression ratio is an independent prognostic marker in colon cancer patients.

PMID- 25773878
TI  - Simultaneous determination of caffeine, paracetamol, and ibuprofen in
      pharmaceutical formulations by high-performance liquid chromatography with UV
      detection and by capillary electrophoresis with conductivity detection.
AB  - Paracetamol, caffeine and ibuprofen are found in over-the-counter pharmaceutical
      formulations. In this work, we propose two new methods for simultaneous
      determination of paracetamol, caffeine and ibuprofen in pharmaceutical
      formulations. One method is based on high-performance liquid chromatography with
      diode-array detection and the other on capillary electrophoresis with
      capacitively coupled contactless conductivity detection. The separation by high
      performance liquid chromatography with diode-array detection was achieved on a
      C18 column (250*4.6 mm(2), 5 MUm) with a gradient mobile phase comprising 20-100%
      acetonitrile in 40 mmol L(-1) phosphate buffer pH 7.0. The separation by
      capillary electrophoresis with capacitively coupled contactless conductivity
      detection was achieved on a fused-silica capillary (40 cm length, 50 MUm i.d.)
      using 10 mmol L(-1) 3,4-dimethoxycinnamate and 10 mmol L(-1) beta-alanine with pH
      adjustment to 10.4 with lithium hydroxide as background electrolyte. The
      determination of all three pharmaceuticals was carried out in 9.6 min by liquid
      chromatography and in 2.2 min by capillary electrophoresis. Detection limits for
      caffeine, paracetamol and ibuprofen were 4.4, 0.7, and 3.4 MUmol L(-1) by liquid
      chromatography and 39, 32, and 49 MUmol L(-1) by capillary electrophoresis,
      respectively. Recovery values for spiked samples were between 92-107% for both
      proposed methods.

PMID- 25773879
TI  - Correlation of the impedance and effective electrode area of doped PEDOT modified
      electrodes for brain-machine interfaces.
AB  - Electrode impedance is used to assess the thermal noise and signal-to-noise ratio
      for brain-machine interfaces. An intermediate frequency of 1 kHz is typically
      measured, although other frequencies may be better predictors of device
      performance. PEDOT-PSS, PEDOT-DBSA and PEDOT-pTs conducting polymer modified
      electrodes have reduced impedance at 1 kHz compared to bare metal electrodes, but
      have no correlation with the effective electrode area. Analytical solutions to
      impedance indicate that all low-intermediate frequencies can be used to compare
      the electrode area at a series RC circuit, typical of an ideal metal electrode in
      a conductive solution. More complex equivalent circuits can be used for the
      modified electrodes, with a simplified Randles circuit applied to PEDOT-PSS and
      PEDOT-pTs and a Randles circuit including a Warburg impedance element for PEDOT
      DBSA at 0 V. The impedance and phase angle at low frequencies using both
      equivalent circuit models is dependent on the electrode area. Low frequencies may
      therefore provide better predictions of the thermal noise and signal-to-noise
      ratio at modified electrodes. The coefficient of variation of the PEDOT-pTs
      impedance at low frequencies was lower than the other conducting polymers,
      consistent with linear and steady-state electroactive area measurements. There
      are poor correlations between the impedance and the charge density as they are
      not ideal metal electrodes. 

PMID- 25773881
TI  - Tracking the metabolic pulse of plant lipid production with isotopic labeling and
      flux analyses: Past, present and future.
AB  - Metabolism is comprised of networks of chemical transformations, organized into
      integrated biochemical pathways that are the basis of cellular operation, and
      function to sustain life. Metabolism, and thus life, is not static. The rate of
      metabolites transitioning through biochemical pathways (i.e., flux) determines
      cellular phenotypes, and is constantly changing in response to genetic or
      environmental perturbations. Each change evokes a response in metabolic pathway
      flow, and the quantification of fluxes under varied conditions helps to elucidate
      major and minor routes, and regulatory aspects of metabolism. To measure fluxes
      requires experimental methods that assess the movements and transformations of
      metabolites without creating artifacts. Isotopic labeling fills this role and is
      a long-standing experimental approach to identify pathways and quantify their
      metabolic relevance in different tissues or under different conditions. The
      application of labeling techniques to plant science is however far from reaching
      it potential. In light of advances in genetics and molecular biology that provide
      a means to alter metabolism, and given recent improvements in instrumentation,
      computational tools and available isotopes, the use of isotopic labeling to probe
      metabolism is becoming more and more powerful. We review the principal analytical
      methods for isotopic labeling with a focus on seminal studies of pathways and
      fluxes in lipid metabolism and carbon partitioning through central metabolism.
      Central carbon metabolic steps are directly linked to lipid production by serving
      to generate the precursors for fatty acid biosynthesis and lipid assembly.
      Additionally some of the ideas for labeling techniques that may be most
      applicable for lipid metabolism in the future were originally developed to
      investigate other aspects of central metabolism. We conclude by describing recent
      advances that will play an important future role in quantifying flux and
      metabolic operation in plant tissues. 

PMID- 25773880
TI  - Learning trajectories for speech motor performance in children with specific
      language impairment.
AB  - Children with specific language impairment (SLI) often perform below expected
      levels, including on tests of motor skill and in learning tasks, particularly
      procedural learning. In this experiment we examined the possibility that children
      with SLI might also have a motor learning deficit. Twelve children with SLI and
      thirteen children with typical development (TD) produced complex nonwords in an
      imitation task. Productions were collected across three blocks, with the first
      and second blocks on the same day and the third block one week later. Children's
      lip movements while producing the nonwords were recorded using an Optotrak camera
      system. Movements were then analyzed for production duration and stability.
      Movement analyses indicated that both groups of children produced shorter
      productions in later blocks (corroborated by an acoustic analysis), and the rate
      of change was comparable for the TD and SLI groups. A nonsignificant trend for
      more stable productions was also observed in both groups. SLI is regularly
      accompanied by a motor deficit, and this study does not dispute that. However,
      children with SLI learned to make more efficient productions at a rate similar to
      their peers with TD, revealing some modification of the motor deficit associated
      with SLI. LEARNING OUTCOMES: The reader will learn about deficits commonly
      associated with specific language impairment (SLI) that often occur alongside the
      hallmark language deficit. The authors present an experiment showing that
      children with SLI improved speech motor performance at a similar rate compared to
      typically developing children. The implication is that speech motor learning is
      not impaired in children with SLI.

PMID- 25773882
TI  - Assessment of temporal resolution of multi-detector row computed tomography in
      helical acquisition mode using the impulse method.
AB  - The purpose of this study was to propose a method for assessing the temporal
      resolution (TR) of multi-detector row computed tomography (CT) (MDCT) in the
      helical acquisition mode using temporal impulse signals generated by a metal ball
      passing through the acquisition plane. An 11-mm diameter metal ball was shot
      along the central axis at approximately 5 m/s during a helical acquisition, and
      the temporal sensitivity profile (TSP) was measured from the streak image
      intensities in the reconstructed helical CT images. To assess the validity, we
      compared the measured and theoretical TSPs for the 4-channel modes of two MDCT
      systems. A 64-channel MDCT system was used to compare TSPs and image quality of a
      motion phantom for the pitch factors P of 0.6, 0.8, 1.0 and 1.2 with a rotation
      time R of 0.5 s, and for two R/P combinations of 0.5/1.2 and 0.33/0.8. Moreover,
      the temporal transfer functions (TFs) were calculated from the obtained TSPs. The
      measured and theoretical TSPs showed perfect agreement. The TSP narrowed with an
      increase in the pitch factor. The image sharpness of the 0.33/0.8 combination was
      inferior to that of the 0.5/1.2 combination, despite their almost identical full
      width at tenth maximum values. The temporal TFs quantitatively confirmed these
      differences. The TSP results demonstrated that the TR in the helical acquisition
      mode significantly depended on the pitch factor as well as the rotation time, and
      the pitch factor and reconstruction algorithm affected the TSP shape.

PMID- 25773883
TI  - Microbeam radiation therapy: Clinical perspectives.
AB  - Microbeam radiation therapy (MRT), a novel form of spatially fractionated
      radiotherapy (RT), uses arrays of synchrotron-generated X-ray microbeams (MB).
      MRT has been identified as a promising treatment concept that might be applied to
      patients with malignant central nervous system (CNS) tumours for whom, at the
      current stage of development, no satisfactory therapy is available yet.
      Preclinical experimental studies have shown that the CNS of healthy rodents and
      piglets can tolerate much higher radiation doses delivered by spatially separated
      MBs than those delivered by a single, uninterrupted, macroscopically wide beam.
      High-dose, high-precision radiotherapies such as MRT with reduced probabilities
      of normal tissue complications offer prospects of improved therapeutic ratios, as
      extensively demonstrated by results of experiments published by many
      international groups in the last two decades. The significance of developing MRT
      as a new RT approach cannot be understated. Up to 50% of cancer patients receive
      conventional RT, and any new treatment that provides better tumour control whilst
      preserving healthy tissue is likely to significantly improve patient outcomes. 

PMID- 25773884
TI  - Simultaneous production of mixed electron--photon beam in a medical LINAC: A
      feasibility study.
AB  - PURPOSE: The electron or photon beams might be used for treatment of tumors. Each
      beam has its own advantage and disadvantages. Combo beam can increase the
      advantages. No investigation has been performed for producing simultaneous mixed
      electron and photon beam. In current study a device has been added to the Medical
      Linac to produce a mixed photon-electron beam. METHODS: Firstly a Varian 2300CD
      head was simulated by MCNP Monte Carlo Code. Two sets of perforated lead sheets
      with 1 and 2 mm thickness and 0.2, 0.3, and 0.5 cm punches then placed at the top
      of the applicator holder tray. This layer produces bremsstrahlung x-ray upon
      impinging fraction electrons on it. The remaining fraction of electrons passes
      through the holes. The simulation was performed for 10 * 10, 6 * 6, and 4 * 4
      cm(2) field size. RESULTS: For 10 * 10 cm(2) field size, among the punched
      targets, the largest penumbra difference between the depth of 1 and 7 cm was 72%.
      This difference for photon and electron beams were 31% and 325% respectively. A
      maximum of 39% photon percentage was produced by 2 mm target with 0.2 cm holes
      diameter layer. The minimum surface dose value was 4% lesser than pure electron
      beam. For small fields, unlike the pure electron beam, the PDD, penumbra, and
      flatness variations were negligible. CONCLUSIONS: The advantages of mixing the
      electron and photon beam is reduction of pure electron's penumbra dependency with
      the depth, especially for small fields, also decreasing of dramatic changes of
      PDD curve with irradiation field size.

PMID- 25773885
TI  - Dendritic cell regulation of NK-cell responses involves lymphotoxin-alpha, IL-12,
      and TGF-beta.
AB  - Dendritic cell (DC) vaccines induce T-cell responses in cancer patients. However,
      there is a paucity of data regarding the role of DC vaccines in shaping natural
      killer (NK) cell responses. Here, we observe that NK cells are less activated
      following DC vaccination. In vitro, DC-mediated inhibition of NK cells did not
      require cell-to-cell contact, but required increased Signal transducer and
      activator of transcription 3 (STAT3) phosphorylation (pSTAT3) in DCs. When
      phosphorylation of STAT3 was inhibited in DCs, we found that DCs did not suppress
      NK cells, and observed an increase in the production of lymphotoxin-alpha
      (LTalpha) and interleukin-12 (IL-12) as well as reduced release of transforming
      growth factor beta (TGF-beta). The addition of recombinant LTalpha or IL-12 to
      the DC-NK-cell cocultures restored NK-cell activity, and neutralization of TGF
      beta resulted in elevated production of LTalpha and IL-12 from DCs. Compared with
      LPS, DCs matured with a cocktail of R848, poly I:C, and IFN-gamma showed reduced
      levels of pSTAT3 and higher levels of LTalpha and IL-12 and did not inhibit NK
      cell activity. These results show that LTalpha, IL-12, and TGF-beta are involved
      in the cross-talk between NK cells and DCs. Our findings have important
      implications for the development of DC-based vaccination strategies to potentiate
      NK-cell responses in patients with cancer. 

PMID- 25773886
TI  - Microchimerism in alopecia areata.
AB  - BACKGROUND: Autoimmunity is the main etiopathogenetic factor in alopecia areata.
      Microchimerism is the existence of allogeneic DNA in a living creature. There are
      variable studies investigating the role of microchimerism on the etiopathogenesis
      of autoimmune diseases. To our knowledge, no report has investigated the
      relationship between microchimerism and alopecia areata. OBJECTIVE: We aimed to
      investigate the possible role of microchimerism on alopecia areata. METHODS: We
      analyzed SRY gene levels as indicators of fetal microchimerism in our patient
      group. The patients were 29 women with alopecia areata, over 18 years old, who
      had visited our clinic between 2010 and 2013. Patients were divided into two
      groups; group 1 consisted of 14 patients having a son and group 2, 15 patients
      either nulliparous or having a daughter. RESULTS: Seventeen of 29 patients
      (58.6%) and four of 103 controls (3.9%) showed presence of an SRY gene. The
      difference between the patient and control groups was statistically significant
      (P < 0.001). CONCLUSION: As a result of our study, microchimerism may be
      associated with the etiopathogenesis of alopecia areata. However, we think there
      is a need for a larger series of studies to support this hypothesis.

PMID- 25773887
TI  - Salicylate improves macrophage cholesterol homeostasis via activation of Ampk.
AB  - Atherosclerosis stems from imbalances in lipid metabolism and leads to
      maladaptive inflammatory responses. The AMP-activated protein kinase (Ampk) is a
      highly conserved serine/threonine kinase that regulates many aspects of lipid and
      energy metabolism, although its specific role in controlling macrophage
      cholesterol homeostasis remains unclear. We sought to address this question by
      testing the effects of direct Ampk activators in primary bone marrow-derived
      macrophages from Ampk beta1-deficient (beta1(-/-)) mice. Macrophages from Ampk
      beta1(-/-) mice had enhanced lipogenic capacity and diminished cholesterol
      efflux, although cholesterol uptake was unaffected. Direct activation of Ampk
      beta1 via salicylate (the unacetylated form of aspirin) or A-769662 (a small
      molecule activator), decreased the synthesis of FAs and sterols in WT but not
      Ampk beta1(-/-) macrophages. In lipid-laden macrophages, Ampk activation
      decreased cholesterol content (foam cell formation) and increased cholesterol
      efflux to HDL and apoA-I, effects that occurred in an Ampk beta1-dependent
      manner. Increased cholesterol efflux was also associated with increased gene
      expression of the ATP binding cassette transporters, Abcg1 and Abca1. Moreover,
      in vivo reverse cholesterol transport was suppressed in mice that received Ampk
      beta1(-/-) macrophages compared with the WT control. Our data highlight the
      therapeutic potential of targeting macrophage Ampk with new or existing drugs for
      the possible reduction in foam cell formation during the early stages of
      atherosclerosis. 

PMID- 25773889
TI  - Tracing vocal fold vibrations using level set segmentation method.
AB  - High-speed digital imaging (HSDI) of the larynx can provide important information
      on the vocal fold kinematics. This information is useful and may provide a better
      understanding of the mechanism of phonation and assist clinical assessment of
      voice disorders. Automatic tracing of the vocal fold vibration is a key step in
      the kinematic analysis and for correlative characterization of vocal fold
      vibrations and voice quality in normal and diseased states. In this study, we
      introduce a new approach for image segmentation and automatic tracing of vocal
      fold motion that combines the level set method and motion cue. This approach is
      applied to videokymogram (VKG)-form images, which are obtained from a sequence of
      laryngeal images captured using the HSDI. To utilize the motion cue for a more
      effective level set based segmentation on the VKG, we first construct a so-called
      standard deviation (STD) image by mapping the pixel-based measure of temporal
      intensity dispersion from the initial HSDI sequence. The STD image maps the
      extent of vocal fold motion, and followed by threshold operation, a region of
      interest (ROI) that encloses vocal fold motion, or glottal region, is identified.
      The performance and effectiveness of our approach are evaluated by using clinical
      datasets representing both normal and pathological voice conditions.

PMID- 25773888
TI  - Lipidomic changes of LDL in overweight and moderately hypercholesterolemic
      subjects taking phytosterol- and omega-3-supplemented milk.
AB  - The benefits of dietary phytosterols (PhySs) and long-chain n-3 PUFA (omega3)
      have been linked to their effects as cholesterol- and triglyceride (TGL)-lowering
      agents. However, it remains unknown whether these compounds have further
      metabolic effects on LDL lipid composition. Here, we studied the effects of PhyS-
      or omega3-supplemented low-fat milk (milk) on the LDL-lipidome. Overweight and
      moderately hypercholesterolemic subjects (n = 32) were enrolled in a two-arm
      longitudinal crossover study. Milk (250 ml/day), enriched with either 1.57 g PhyS
      or 375 mg omega3 (EPA + DHA), was given to the participants during two sequential
      28 day intervention periods. Compared with baseline, PhyS-milk induced a higher
      reduction in the LDL cholesterol (LDLc) level than omega3-milk. LDL resistance to
      oxidation was significantly increased after intervention with PhyS-milk. Changes
      in TGL and VLDL cholesterol were only evident after omega3-milk intake. Lipidomic
      analysis revealed a differential effect of the PhyS- and omega3-milk
      interventions on the LDL lipid metabolite pattern. Content in LDL
      glycerophospholipids was reduced after PhyS-milk intake, with major changes in
      phosphatidylcholine (PC) and phosphatidylserine subclasses, whereas omega3-milk
      induced significant changes in the long-chain polyunsaturated cholesteryl esters
      and in the ratio PC36:5/lysoPC16:0, associated to a reduced inflammatory
      activity. In conclusion, daily intake of milk products containing PhyS or omega3
      supplements induce changes in the LDL-lipidome that indicate reduced inflammatory
      and atherogenic effects, beyond their LDLc- and TGL-lowering effects. 

PMID- 25773890
TI  - Fuzzy-GA modeling in air quality assessment.
AB  - In this paper, the authors have suggested and implemented the defined soft
      computing methods in air quality classification with case studies. The first
      study relates to the application of Fuzzy C mean (FCM) clustering method in
      estimating pollution status in cities of Maharashtra State, India. In this study,
      the computation of weighting factor using a new concept of reference group is
      successfully demonstrated. The authors have also investigated the efficacy of
      fuzzy set theoretic approach in combination with genetic algorithm in straightway
      describing air quality in linguistic terms with linguistic degree of certainty
      attached to each description using Zadeh-Deshpande (ZD) approach. Two
      metropolitan cities viz., Mumbai in India and New York in the USA are identified
      for the assessment of the pollution status due to their somewhat similar
      geographical features. The case studies infer that the fuzzy sets drawn on the
      basis of expert knowledge base for the criteria pollutants are not much different
      from those obtained using genetic algorithm. Pollution forecast using various
      methods including fuzzy time series forms an integral part of the paper. 

PMID- 25773891
TI  - Metal bioconcentration in the scleractinian coral Stylophora pistillata:
      investigating the role of different components of the holobiont using
      radiotracers.
AB  - Bioconcentration kinetics of five metals (Ag, Cd, Co, Mn, and Zn) were determined
      in the scleractinian coral Stylophora pistillata (entire symbiotic association
      vs. cultured symbionts), using radiotracer techniques. Among contrasting element
      behaviors observed in S. pistillata, the highest efficiency of concentration and
      retention was observed for Ag in the symbiotic association (CFss reaching 5000
      and T b1/2>1 year). Predominant proportion of this metal was found associated
      with the skeleton whereas the other metals were mainly present in the coral
      tissues (including host tissues and symbionts). A 96-h exposure of cultured
      symbionts (isolated zooxantellae from S. pistillata) indicated that they
      displayed a very high potential for metal bioconcentration (higher by 1 to 3
      orders of magnitude compared to the skeleton). In addition, among the five
      elements investigated, Ag had the highest concentration factor in the cultured
      symbionts. Contrasting kinetic characteristics of skeleton vs. tissues offer
      interesting implications for biomonitoring purposes. Indeed, the skeleton was
      shown to display stable metal concentrations after an exposure (long retention
      time) and thereby allows recording contamination event on the long term, whereas
      the concentrations within coral tissues rapidly increased during the exposure and
      dropped when non-contaminating conditions were restored, allowing information on
      the current (short term) contamination status. The present study confirms that
      the coral can be seen as a two-compartment box model for metal bioconcentration:
      the tissues sensus latto as a first box governing metal entrance (with a crucial
      role played by the symbionts) and the skeleton as a second box where metal
      detoxification (storage) is taking place; the first box also depurates toward the
      environment when non-contaminating conditions are restored.

PMID- 25773892
TI  - Evaluation of the environmental sustainability of farmers' land use decisions in
      the saline-alkaline areas.
AB  - Environmental sustainability has become the focus of agricultural sustainability.
      This study is aimed at evaluating the environmental sustainability of farmers'
      land use decisions on saline-alkaline soil in China. Based on empirical and
      theoretical approaches, the decisions mainly include planting, crop distribution,
      irrigation, drainage, and fertilization. By surveying 22 administrative villages
      in typical ecologically fragile saline-alkaline areas of five regions (Shandong,
      Jiangsu, Jilin, Ningxia, and Xinjiang), the paper builds the evaluation criteria
      at village level, and obtains a comprehensive index. From the results, irrigation
      concerns are absent from decision-making. For other decisions, farmers in most
      villages can appropriately deal with planting, drainage, and fertilization
      according to the regional natural and social geography conditions. But the
      comprehensive index of crop distribution in the coastal areas is much stronger
      than in the northeast and northwest. It is found that the similarities of
      unsustainability lie in the planting of water-consuming crops, the arbitrary
      distribution of crops, lack of drainage planning, obsolete water conservancy
      facilities, excessive use of chemical fertilizers, etc. According to the
      research, on the one hand, it can guide farmers to rationally make use of saline
      alkaline land; on the other hand, it can also provide the basis for government to
      make differentiated policies in different areas and enhance pertinence in the
      course of technological extension and application. 

PMID- 25773893
TI  - Aflatoxins B1, B2, G1, and G2 contamination in ground red peppers commercialized
      in Sanliurfa, Turkey.
AB  - Aflatoxins (AFs) are hepatogenic, teratogenic, imunosuppressive, and carcinogenic
      fungal metabolites found in feeds, nuts, wine-grapes, spices, and other grain
      crops. Humans are exposed to AFs via consumption of mycotoxin-contaminated foods.
      This study aimed to determine the prevalence of AF contamination in powdered red
      peppers sold in Sanliurfa. A total of 42 samples were randomly collected from
      retail shops, supermarkets, open bazaars, and apiaries and examined for the
      occurrence and levels of AFB1, AFB2, AFG1, and AFG2 toxins. AFs were determined
      by using an HPLC system after pre-separation utilizing immunoaffinity columns.
      AFs levels were below 2.5 MUg/kg in 16 samples, between 2.5 and 10 MUg/kg in 13
      samples while 13 samples had AFs higher than the tolerable limit (10 MUg/kg)
      according to the regulations of Turkish Food Codex and European Commission. The
      occurrence of AF fractions during powdered red pepper processing steps was also
      evaluated. According to the results obtained in this study, it was found that the
      highest AF accumulations in powdered red peppers start during perspiration and
      final drying of the products processed on soil contacted surfaces while there was
      no limit exceeding aflatoxin contamination in the samples produced on concrete
      surfaces. 

PMID- 25773894
TI  - A toxicity scoring system for the 10-day whole sediment test with Corophium
      insidiosum (Crawford).
AB  - This study developed a tool able to evaluate the potential contamination of
      marine sediments detecting the presence or absence of toxicity supporting
      environmental decision-making processes. When the sample is toxic, it is
      important to classify its level of toxicity to understand its subsequent effects
      and management practices. Corophium insidiosum is a widespread and frequently
      recorded species along the Mediterranean Sea, North Sea and western Baltic Sea
      with records also in the Atlantic Ocean and Pacific Ocean. This amphipod is found
      in high abundance in shallow brackish inshore areas and estuaries also with high
      turbidity. At Italian level, C. insidiosum is more frequently collectable than
      Corophium orientale, making routine toxicity tests easier to be performed.
      Moreover, according to the international scientific literature, C. insidiosum is
      more sensitive than C. orientale. Whole sediment toxicity data (10 days) with C.
      insidiosum were organised in a species-specific toxicity score on the basis of
      the minimum significance difference (MSD) approach. Thresholds to rank samples as
      non-toxic and toxic were based on sediment samples (n=84) from the Gulf of
      Taranto (Italy). A five-class toxicity score (absent, low, medium, high and very
      high toxicity) was developed, considering the distribution of the 90th percentile
      of the MSD normalised to the effects on the negative controls (samples from
      reference sites). This toxicity score could be useful for interpreting sediment
      potential impacts and providing quick responsive management information.

PMID- 25773895
TI  - Coupling of remote sensing, field campaign, and mechanistic and empirical
      modeling to monitor spatiotemporal carbon dynamics of a Mediterranean watershed
      in a changing regional climate.
AB  - The aim of this study was to simulate impacts of regional climate change in the
      2070s on carbon (C) cycle of a Mediterranean watershed combining field
      measurements, Envisat MERIS and IKONOS data, and the Carnegie Ames Stanford
      Approach model. Simulation results indicated that the present total C sink status
      (1.36 Mt C year(-1)) of Mediterranean evergreen needleleaf forest, grassland and
      cropland ecosystems is expected to weaken by 7.6% in response to the climate
      change in the 2070s (Mt=10(12) g). This decreasing trend was mirrored in soil
      respiration (R H), aboveground and belowground net primary production (NPP), NEP,
      and net biome production (NBP). The decrease in NEP in the 2070s was the highest
      (21.9%) for mixed forest where the smallest present C sink of 0.03 Mt C year(-1)
      was estimated. The average present net ecosystem production (NEP) values were
      estimated at 110+/-15, 75+/-19, and 41+/-25 g C m(-2) years(-1) in forest,
      grassland, and cropland, respectively, with a watershed-scale mean of 95+/-30 g C
      m(-2) years(-1). The largest present C sink was in grassland, with a total C pool
      of 0.55 Mt C year(-1), through its greater spatial extent.

PMID- 25773896
TI  - Geostatistical approach for management of soil nutrients with special emphasis on
      different forms of potassium considering their spatial variation in intensive
      cropping system of West Bengal, India.
AB  - A large part of precision agriculture research in the developing countries is
      devoted towards precision nutrient management aspects. This has led to better
      economics and efficiency of nutrient use with off-farm advantages of
      environmental security. The keystone of precision nutrient management is analysis
      and interpretation of spatial variability of soils by establishing management
      zones. In this study, spatial variability of major soil nutrient contents was
      evaluated in the Ghoragacha village of North 24 Parganas district of West Bengal,
      India. Surface soil samples from 100 locations, covering different cropping
      systems of the village, was collected from 0 to 15 cm depth using 100*100 m grid
      system and analyzed in the laboratory to determine organic carbon (OC), available
      nitrogen (N), phosphorus (P), and potassium (K) contents of the soil as well as
      its water-soluble K (KWS), exchangeable K (KEX), and non-exchangeable forms of K
      (KNEX). Geostatistical analyses were performed to determine the spatial variation
      structure of each nutrient content within the village, followed by the generation
      of surface maps through kriging. Four commonly used semivariogram models, i.e.,
      spherical, exponential, Gaussian, and linear models were fitted to each soil
      property, and the best one was used to prepare surface maps through krigging.
      Spherical model was found the best for available N and P contents, while linear
      and exponential model was the best for OC and available K, and for KWS and KNEK,
      Gausian model was the best. Surface maps of nutrient contents showed that N
      content (129-195 kg ha(-1)) was the most limiting factor throughout the village,
      while P status was generally very high ( 10-678 kg ha(-1)) in the soils of the
      present village. Among the different soil K fractions, KWS registered the maximum
      variability (CV 75%), while the remaining soil K fractions showed moderate to
      high variation. Interestingly, KNEX content also showed high variability, which
      essentially indicates reserve native K exploitation under intensive cultivation.
      These maps highlight the necessity of estimating the other soil K fractions as
      well for better understanding of soil K supplying capacity and K fertilization
      strategy rather than the current recommendations, based on the plant-available K
      alone. In conclusion, the present study revealed that the variability of nutrient
      distribution was a consequence of complex interactions between the cropping
      system, nutrient application rates, and the native soil characteristics, and such
      interactions could be utilized to develop the nutrient management strategies for
      intensive small-holder system.

PMID- 25773897
TI  - A novel computer-aided multivariate water quality index.
AB  - A computer-aided multivariate water quality index is developed based on partial
      least squares (PLS) regression. The index is termed as the partial least squares
      water quality index (PLS-WQI). Briefly, a training set was computationally
      generated based on the guideline of National Water Quality Standards for Malaysia
      (NWQS) to predict the water quality. The index is benchmarked with the well
      established index developed by the Department of Environment, Malaysia (DOE-WQI).
      The PLS-WQI is a continuous variable with the value closer to I indicating good
      water quality and closer to V indicating poor water quality. Unlike other
      conventional indexing methods, the algorithm calculates the index in a
      multivariate manner. The algorithm allows rapid processing of a large dataset
      without tedious calculation; it can be an efficient tool for spatial and temporal
      routine monitoring of water quality. Although the algorithm is designed based on
      the guideline of NWQS, it can be easily adapted to accommodate other guidelines.
      The algorithm was evaluated and demonstrated on the simulated and real datasets.
      Results indicate that the algorithm is robust and reliable. Based on six
      parameters, the overall ratings derived are inversely correlated to DOE-WQI. When
      the number of parameter is increased, the overall ratings appear to provide
      better insights into the water quality. 

PMID- 25773898
TI  - What plant hydraulics can tell us about responses to climate-change droughts.
AB  - Climate change exposes vegetation to unusual drought, causing declines in
      productivity and increased mortality. Drought responses are hard to anticipate
      because canopy transpiration and diffusive conductance (G) respond to drying soil
      and vapor pressure deficit (D) in complex ways. A growing database of hydraulic
      traits, combined with a parsimonious theory of tree water transport and its
      regulation, may improve predictions of at-risk vegetation. The theory uses the
      physics of flow through soil and xylem to quantify how canopy water supply
      declines with drought and ceases by hydraulic failure. This transpiration 'supply
      function' is used to predict a water 'loss function' by assuming that stomatal
      regulation exploits transport capacity while avoiding failure. Supply-loss theory
      incorporates root distribution, hydraulic redistribution, cavitation
      vulnerability, and cavitation reversal. The theory efficiently defines stomatal
      responses to D, drying soil, and hydraulic vulnerability. Driving the theory with
      climate predicts drought-induced loss of plant hydraulic conductance (k), canopy
      G, carbon assimilation, and productivity. Data lead to the 'chronic stress
      hypothesis' wherein > 60% loss of k increases mortality by multiple mechanisms.
      Supply-loss theory predicts the climatic conditions that push vegetation over
      this risk threshold. The theory's simplicity and predictive power encourage
      testing and application in large-scale modeling.

PMID- 25773899
TI  - Evaluation of older adult patients with falls in the emergency department:
      discordance with national guidelines.
AB  - OBJECTIVES: The objective was to examine whether the emergency department (ED)
      evaluation of older adult fallers is concordant with the Geriatric Emergency
      Department Guidelines. METHODS: This study was a chart review of randomly
      selected older adult ED fall patients from one urban academic teaching hospital.
      Patients 65 years and older who had ED fall visits in 2012 and who had primary
      care physicians within our hospital network during the past 3 years were
      included. Transferred patients were excluded. The data collection instrument was
      adapted from ED fall evaluation recommendations. RESULTS: There were 350 patients
      in this study. The mean (+/-SD) patient age was 80.1 (+/-8.8) years, 124 (35%)
      were male, 327 (93%) were white, and 298 (85%) were community dwelling. The range
      with which history and physical examination findings were concordant with fall
      guidelines was 1% to 85%. Cause and location of fall were the two most frequently
      reported history items (85 and 81%, respectively), while asking about baseline
      vision was only reported 1% of the time. Evaluating for sensory deficits and
      muscle strength were the two most frequently reported physical examinations (63
      and 48%, respectively), while balance was evaluated with the lowest frequency
      (1%). Patients who received more guideline-recommended evaluations were older
      with more comorbid conditions and were transferred to an observation unit or
      admitted to the hospital more frequently. Overall, more than half of these
      elderly patients (56%) were discharged from the ED to their place of preadmission
      residence. CONCLUSIONS: The current ED evaluation of older adult fallers is
      discordant with general and ED-specific fall guidelines. Future studies are
      warranted to investigate ways to successfully implement fall evaluation
      guidelines.

PMID- 25773900
TI  - Ion trap with narrow aperture detection electrodes for Fourier transform ion
      cyclotron resonance mass spectrometry.
AB  - The current paradigm in ion trap (cell) design for Fourier transform ion
      cyclotron resonance mass spectrometry (FT-ICR MS) is the ion detection with wide
      aperture detection electrodes. Specifically, excitation and detection electrodes
      are typically 90 degrees  wide and positioned radially at a similar distance from
      the ICR cell axis. Here, we demonstrate that ion detection with narrow aperture
      detection electrodes (NADEL) positioned radially inward of the cell's axis is
      feasible and advantageous for FT-ICR MS. We describe design details and
      performance characteristics of a 10 T FT-ICR MS equipped with a NADEL ICR cell
      having a pair of narrow aperture (flat) detection electrodes and a pair of
      standard 90 degrees  excitation electrodes. Despite a smaller surface area of the
      detection electrodes, the sensitivity of the NADEL ICR cell is not reduced
      attributable to improved excite field distribution, reduced capacitance of the
      detection electrodes, and their closer positioning to the orbits of excited ions.
      The performance characteristics of the NADEL ICR cell are comparable with the
      state-of-the-art FT-ICR MS implementations for small molecule, peptide, protein,
      and petroleomics analyses. In addition, the NADEL ICR cell's design improves the
      flexibility of ICR cells and facilitates implementation of advanced capabilities
      (e.g., quadrupolar ion detection for improved mainstream applications). It also
      creates an intriguing opportunity for addressing the major bottleneck in FTMS
      increasing its throughput via simultaneous acquisition of multiple transients or
      via generation of periodic non-sinusoidal transient signals. 

PMID- 25773901
TI  - Characterization of protein alterations in damaged axons in the brainstem
      following traumatic brain injury using fourier transform infrared
      microspectroscopy: a preliminary study.
AB  - Axonal injury contributes greatly to neurological dysfunction following traumatic
      brain injury (TBI), but current histological diagnostic methods are limited in
      identifying the pathological profiles of injured axons and unable to provide an
      objective and accurate quantification. Fourier transform infrared
      microspectroscopy (FTIRM) has the ability to offer macromolecular bioinformatics
      of the tissues including biochemical composition and structure by calculating
      band absorption intensity. In this study, axonal injury in the brainstem of rats
      with traumatic brain injury at 72 h post-trauma, which was confirmed with beta
      amyloid precursor protein (beta-APP) immunostaining, was detected with FTIRM
      technique. The lower intensity of infrared absorbance under the amide I band
      corresponds strongly to the area of axonal injury, and further analysis of amide
      I band shows significant differences in protein conformation between injured and
      normal axons. The findings indicate that using FTIRM technique, the amide I band
      has potentials to be a infrared spectral marker of axonal injury.

PMID- 25773902
TI  - Statistics in Brief: An Introduction to the Use of Propensity Scores.

PMID- 25773903
TI  - Obituary: Victor M. Goldberg MD (1939-2015)--a remembrance.

PMID- 25773904
TI  - CORR Insights(r): What Host Factors Affect Aseptic Loosening After THA and TKA?

PMID- 25773905
TI  - Editorial: What Makes Young Surgeons Tick (or Cut)?

PMID- 25773906
TI  - Use of enoxaparin in dogs with primary immune-mediated hemolytic anemia: 21
      cases.
AB  - OBJECTIVE: To describe the complications and frequency of thrombosis associated
      with the use of enoxaparin, a low molecular weight heparin, in dogs with primary
      immune-mediated hemolytic anemia (IMHA). DESIGN: Retrospective case series.
      SETTING: Two privately owned veterinary referral hospitals. ANIMALS: Twenty-one
      client-owned dogs with primary IMHA. INTERVENTIONS: Dogs were treated with
      enoxaparin (0.8 mg/kg subcutaneously every 6 h) as the sole anticoagulation
      therapy starting at admission to the hospital. MEASUREMENTS AND MAIN RESULTS:
      Only 2 dogs had minor hemorrhagic complications associated with enoxaparin
      therapy. Frequency of thrombosis was not assessed. Long-term survival was
      comparable to other anticoagulation protocols reported for dogs with primary
      IMHA. CONCLUSIONS: The use of enoxaparin was safe in a small group of dogs with
      primary IMHA. Whether enoxaparin therapy can reduce mortality and thrombotic
      complications in dogs with primary IMHA compared with other anticoagulation
      protocols remains unknown.

PMID- 25773907
TI  - New arylpiperazinylalkyl derivatives of 8-alkoxy-purine-2,6-dione and
      dihydro[1,3]oxazolo[2,3-f]purinedione targeting the serotonin 5-HT1A /5-HT2A /5
      HT7 and dopamine D2 receptors.
AB  - To obtain potential antidepressants and/or antipsychotics, a series of new long
      chain arylpiperazine derivatives of 8-alkoxy-purine-2,6-dione (10-24) and
      dihydro[1,3]oxazolo[2,3-f]purinedione (30-34) were synthesized and their
      serotonin (5-HT1A , 5-HT2A , 5-HT6 , 5-HT7 ) and dopamine (D2 ) receptor
      affinities were determined. The study allowed the identification of some potent 5
      HT1A /5-HT7 /D2 ligands with moderate affinity for 5-HT2A sites. The binding mode
      of representative compounds from both chemical classes (11 and 31) in the site of
      5-HT1A receptor was analyzed in computational studies. In functional in vitro
      studies, the selected compounds 15 and 16 showed antagonistic properties for the
      evaluated receptors. 8-Methoxy-7-{4-[4-(2-methoxyphenyl)-piperazin-1-yl]-butyl}
      1,3-dimethyl-purine-2,6-dione (15) showed a lack of activity in terms and under
      the conditions of the forced swim, four plate and amphetamine-induced
      hyperactivity tests in mice, probably as a result of its high first pass effect
      in the liver.

PMID- 25773908
TI  - Embigin is overexpressed in pancreatic ductal adenocarcinoma and regulates cell
      motility through epithelial to mesenchymal transition via the TGF-beta pathway.
AB  - Embigin is a member of the immunoglobulin superfamily and encodes a transmembrane
      glycoprotein. There have been reports of Embigin involvement in neuromuscular
      junction formation and plasticity; however, the molecular functions of Embigin in
      other organs are unknown. Our aim was to investigate the possible role of Embigin
      in pancreatic cancer. In pancreatic ductal adenocarcinoma tissues, Embigin
      expression was higher than that in normal pancreatic tissues. Immunohistochemical
      analysis revealed expression of Embigin in pancreatic cancer cells, as well as
      expression of monocarboxylate transporter 2 (MCT2) in cancer tissues. To gain
      further insight, we transfected BxPC-3 and HPAC pancreatic cancer cells with
      siRNA or shRNA targeting Embigin and observed reductions in cell proliferation,
      migration, invasion, wound healing, and reduced levels of matrix
      metalloproteinases-2 and -9. Silencing of Embigin increased intracellular L
      lactate concentration by 1.5-fold and decreased MCT2 levels at the plasma
      membrane. Furthermore, Embigin silencing led to a reduced expression of PI3K,
      GSK3-beta, and Snail/Slug. Upon treating BxPC-3 cells with transforming growth
      factor-beta (TGF-beta), we observed elevated expression of Snail/Slug, Embigin,
      and Vimentin; meanwhile, when treating cells with SB-216763, a GSK3-beta
      inhibitor, we noted decreases in GSK3-beta, Snail/Slug, and Embigin expression,
      suggesting that the TGF-beta signaling cascade, comprising PI3K, GSK3-beta,
      Snail/Slug, and Embigin signals, mediates epithelial to mesenchymal transition
      (EMT) in pancreatic cancer cells. These findings indicate the involvement of
      Embigin in EMT in pancreatic cancer progression and suggest Embigin as a putative
      target for the detection and/or treatment of pancreatic cancer.

PMID- 25773909
TI  - Do the right thing: the assumption of optimality in lay decision theory and
      causal judgment.
AB  - Human decision-making is often characterized as irrational and suboptimal. Here
      we ask whether people nonetheless assume optimal choices from other decision
      makers: Are people intuitive classical economists? In seven experiments, we show
      that an agent's perceived optimality in choice affects attributions of
      responsibility and causation for the outcomes of their actions. We use this
      paradigm to examine several issues in lay decision theory, including how
      responsibility judgments depend on the efficacy of the agent's actual and
      counterfactual choices (Experiments 1-3), individual differences in
      responsibility assignment strategies (Experiment 4), and how people conceptualize
      decisions involving trade-offs among multiple goals (Experiments 5-6). We also
      find similar results using everyday decision problems (Experiment 7). Taken
      together, these experiments show that attributions of responsibility depend not
      only on what decision-makers do, but also on the quality of the options they
      choose not to take. 

PMID- 25773910
TI  - Isolated neurosarcoidosis mimicking intracranial tumours - Analysis of 3 cases.
AB  - Isolated neurosarcoidosis (INS), as a disease of low prevalence, is commonly
      overlooked in differential diagnosis, and its discovery on histopathological
      examination usually comes as a surprise. Preoperative diagnosis is difficult
      because the clinical picture of INS is non-specific. Its symptoms depend on the
      location of the lesions, and the MRI results are similar to those found in
      meningiomas or optic nerve gliomas. Although up to 5% of all sarcoidosis patients
      present with neurological symptoms, those with INS are exceptionally infrequently
      encountered. Three cases of INS are presented here, analysing their clinical
      course and radiological images, in order to determine characteristic traits that
      might lead to a correct diagnosis. 

PMID- 25773911
TI  - Pyoderma gangrenosum associated with solid organ malignancies.
AB  - BACKGROUND: Pyoderma gangrenosum (PG) can be associated with systemic diseases,
      including inflammatory bowel disease, inflammatory arthritis, and hematologic
      malignancy. Previous literature exploring the rare association between PG and
      solid organ malignancy is predominantly limited to single case reports. METHODS:
      We retrospectively reviewed the cases of five patients with PG and solid organ
      malignancies at our institution between 1996 and 2013. RESULTS: For the five
      patients identified, PG and solid organ malignancy occurred within three months
      of each other. Mean age at onset of PG was 55.6 years, and four patients were
      women. Three patients had breast carcinoma (one was recurrent), and two had
      gastrointestinal carcinoma. PG occurred before (n = 2), after (n = 2), or
      synchronously with (n = 1) the malignancy. In one patient with a history of PG
      and quiescent inflammatory bowel disease, recurrent PG developed synchronously
      with a new diagnosis of metastatic rectosigmoid carcinoma. Three patients had
      partial or complete response of PG with treatment of PG alone. CONCLUSIONS: To
      our knowledge, our study is the first to report that the onset of PG can herald a
      recurrence of a solid organ malignancy and that recurrent PG can be associated
      with solid organ malignancy. A possible association of solid organ malignancy and
      PG should be considered in patients with PG of unknown etiology or with a history
      of malignancy.

PMID- 25773912
TI  - Prone positioning induced hepatic necrosis after liver transplantation.

PMID- 25773913
TI  - Ten 'short-lived' beliefs in intensive care medicine.

PMID- 25773914
TI  - Effect of the solvent and the sample preparation on the determination of
      triterpene compounds in two-phase olive-mill-waste samples.
AB  - A simple and rapid extraction method has been employed to determine several value
      added compounds, mainly triterpenes, in two-phase olive-mill-waste samples. The
      compounds were extracted with methanol or ethyl acetate, and the initial fresh
      samples were treated for classic techniques such as drying, drying and oil
      extraction, and drying and sifting of the olive stones. For the identification
      and quantitation of the compounds, an ultra performance liquid chromatography
      mass spectrometry method was employed. The best results of the triterpenic
      compound content were achieved by extraction with methanol from the fresh sample
      for the oleanolic and ursolic acids, and erythrodiol and uvaol; and from the
      dried-extracted sample for the maslinic acid. Conversely, the best results for
      the linoleic acid content were reached by extraction with ethyl acetate from the
      dried-sifted sample. These are remarkable processes that make the solid wastes
      from the olive-oil industry reach a high added value. 

PMID- 25773915
TI  - Experimental and computational investigation of the trajectories of blood drops
      ejected from the nose.
AB  - Blood expirated from the nose may leave a characteristic bloodstain at a crime
      scene which can provide important clues for reconstructing events during a
      violent assault. Little research has been done on the typical velocities,
      trajectories and size distribution that can be expected from expirated blood. An
      experimental fluid dynamics technique known as stereoscopic particle image
      velocimetry is used in this work to obtain the air velocity field inside and
      outside the nostrils during exhalation. A numerical model was then used to
      compute the trajectory of blood drops of 0.5 and 2 mm. The drops were tracked
      until ground plane impact below the nostril exit. Three heights were
      investigated, 1.5, 1.6 and 1.7 m. For an expiration flow rate of 32 l/min in
      vivo, there is a maximum exit velocity from the nostril of approximately 4 m/s,
      with a 0.5 m/s difference between nostrils. After the drops have traversed the
      distances investigated, drops of 0.5 and 2 mm in diameter from both nostrils are
      at a similar velocity. This implies that the gravitational acceleration after the
      drops leave the jet has the most influence on velocity. It is however shown that
      exit velocity does affect impact location. Drop size affects both impact location
      and impact velocity. An increase in height increases the distance traversed.
      Compared to the 2-mm drop, the 0.5 mm had a lower impact velocity, but its impact
      location in the ground plane was further from the nostril exit. Understanding the
      physics of expirated blood flight allows better interpretation of expirated
      stains at crime scenes.

PMID- 25773916
TI  - Detection of aortic rupture using post-mortem computed tomography and post-mortem
      computed tomography angiography by cardiac puncture.
AB  - Post-mortem computed tomography (PMCT) and post-mortem computed tomography
      angiography (PMCTA) are rapidly becoming effective and practical methods in
      forensic medicine. In this article, we introduce a PMCTA approach by cardiac
      puncture and its application in a specific forensic case. A 50-year-old female
      sanitation worker was found dead on a road. External examination of the body
      revealed scattered abrasions and contusions over the chest. Autopsy was refused
      by the family members, and the body was examined with PMCT and PMCTA by cardiac
      puncture. Sternal fracture and rib fractures were detected by PMCT and aortic
      rupture by PMCTA. The cause of death was hemorrhagic shock due to traumatic
      aortic rupture. In certain circumstances, the combination of PMCT and PMCTA is
      helpful for forensic pathologists to determine the cause of death in cases
      involving traumatic vascular injury. 

PMID- 25773917
TI  - Toward the adoption of cementochronology in forensic context.
AB  - Because acellular dental cementum is considered to be formed continually
      throughout life and to not undergo remodeling processes, cementochronology is
      considered to be a method with the potential for directly assessing chronological
      age. Considering that most previous studies on humans have assumed the superior
      performance of this method, it is surprising that this technique is not more
      widely adopted in anthropology. To understand this controversy, we highlight that
      there is no standardized procedure for sample preparation. The numerous technical
      approaches that exist impact the reliability of the method, and the recent
      creation of an international work group (Cementochronology Research Program)
      demonstrates the need for researchers to share their experience to overcome these
      obstacles. This paper aims to address this paradox by debating the aspects that
      contribute to the limited use of this method and by illustrating its potential
      through an application on forensic cases. A protocol, which was recently
      certified according to the ISO-9001, was applied to nine anthropological cases
      from the Forensic Medicine Institute of Lille (northern France) and compared with
      routine osteological and dental methods. The results show that traditional
      methods matched the known age due to the wide extent of their range, while the
      accuracy and precision of cementochronological estimates was also notable. This
      paper establishes that cementochronology may serve as a particularly important
      tool for age estimation for forensic anthropologists and should, at least, be
      used in addition to other methods.

PMID- 25773918
TI  - Discrimination in Healthcare Settings is Associated with Disability in Older
      Adults: Health and Retirement Study, 2008-2012.
AB  - BACKGROUND: As our society ages, improving medical care for an older population
      will be crucial. Discrimination in healthcare may contribute to substandard
      experiences with the healthcare system, increasing the burden of poor health in
      older adults. Few studies have focused on the presence of healthcare
      discrimination and its effects on older adults. OBJECTIVE: We aimed to examine
      the relationship between healthcare discrimination and new or worsened
      disability. DESIGN: This was a longitudinal analysis of data from the nationally
      representative Health and Retirement Study administered in 2008 with follow-up
      through 2012. PARTICIPANTS: Six thousand and seventeen adults over the age of 50
      years (mean age 67 years, 56.3 % female, 83.1 % white) were included in this
      study. MAIN MEASURES: Healthcare discrimination assessed by a 2008 report of
      receiving poorer service or treatment than other people by doctors or hospitals
      (never, less than a year=infrequent; more than once a year=frequent). Outcome was
      self-report of new or worsened disability by 2012 (difficulty or dependence in
      any of six activities of daily living). We used a Cox proportional hazards model
      adjusting for age, race/ethnicity, gender, net worth, education, depression, high
      blood pressure, diabetes, cancer, lung disease, heart disease, stroke, and
      healthcare utilization in the past 2 years. KEY RESULTS: In all, 12.6 %
      experienced discrimination infrequently and 5.9 % frequently. Almost one-third of
      participants (29 %) reporting frequent healthcare discrimination developed new or
      worsened disability over 4 years, compared to 16.8 % of those who infrequently
      and 14.7 % of those who never experienced healthcare discrimination (p < 0.001).
      In multivariate analyses, compared to no discrimination, frequent healthcare
      discrimination was associated with new or worsened disability over 4 years (aHR =
      1.63, 95 % CI 1.16-2.27). CONCLUSIONS: One out of five adults over the age of 50
      years experiences discrimination in healthcare settings. One in 17 experience
      frequent healthcare discrimination, and this is associated with new or worsened
      disability by 4 years. Future research should focus on the mechanisms by which
      healthcare discrimination influences disability in older adults to promote better
      health outcomes for an aging population.

PMID- 25773921
TI  - VO2 nanorods for efficient performance in thermal fluids and sensors.
AB  - VO2 (B) nanorods with average width ranging between 50-100 nm are synthesized via
      a hydrothermal method and the post hydrothermal treatment drying temperature is
      found to be influential in their overall phase and growth morphology evolution.
      The nanorods with unusually high optical bandgap for a VO2 material are effective
      in enhancing the thermal performance of ethylene glycol nanofluids over a wide
      temperature range as is indicated by the temperature dependent thermal
      conductivity measurements. Humidity and LPG sensors fabricated using the VO2 (B)
      nanorods bear testament to their efficient sensing performance, which can be
      partially attributed to the mesoporous nature of the nanorods. 

PMID- 25773920
TI  - Amide-controlled, one-pot synthesis of tri-substituted purines generates
      structural diversity and analogues with trypanocidal activity.
AB  - A novel one-pot synthesis of tri-substituted purines and the discovery of purine
      analogues with trypanocidal activity are reported. The reaction is initiated by a
      metal-free oxidative coupling of primary alkoxides and diaminopyrimidines with
      Schiff base formation and subsequent annulation in the presence of large N,N
      dimethylamides (e.g. N,N-dimethylpropanamide or larger). This synthetic route is
      in competition with a reaction previously-reported by our group, allowing the
      generation of a combinatorial library of tri-substituted purines by the simple
      modification of the amide and the alkoxide employed. Among the variety of
      structures generated, two purine analogues displayed trypanocidal activity
      against the protozoan parasite Trypanosoma brucei with IC50 < 5 MUM, being each
      of those compounds obtained through each of the synthetic pathways.

PMID- 25773922
TI  - Effects of Case Studies and Simulated Patients on Students' Nursing Care Plan.
AB  - PURPOSE: The aim of this study is to determine the effects of using case studies
      and simulated patients in teaching students to plan their nursing care. METHODS:
      The study sample consisted of 70 second-year nursing students. Study data were
      collected using a questionnaire and by evaluating students' nursing care plans.
      RESULTS: The highest percentages of diagnoses identified were altered oral mucous
      membrane, ineffective breathing pattern, disturbed sleep pattern: less than body
      requirement, impaired tissue integrity, pain, and risk for infection.
      CONCLUSIONS: The use of simulated patients in nursing education appears to help
      students evaluate realistic medical cases and clinical problems, and plan their
      nursing care.

PMID- 25773923
TI  - Cancer risks and perspectives: molecular mechanisms.

PMID- 25773924
TI  - 15-Deoxy-Delta12,14-prostaglandin J2 induces expression of 15
      hydroxyprostaglandin dehydrogenase through Elk-1 activation in human breast
      cancer MDA-MB-231 cells.
AB  - Overproduction of prostaglandin E2 (PGE2) has been reported to be implicated in
      carcinogenesis. The intracellular level of PGE2 is maintained not only by its
      biosynthesis, but also by inactivation/degradation. 15-Hydroxyprostaglandin
      dehydrogenase (15-PGDH) is the key enzyme that catalyzes the conversion of
      oncogenic PGE2 to a biologically inactive keto metabolite. In the present study,
      we demonstrate that 15-deoxy-Delta(12,14)-prostaglandin J2 (15 d-PGJ2), one of
      the terminal products of cyclooxygenase-2, updregulates the expression and the
      activity of 15-PGDH in human breast cancer MDA-MB-231 cells. By using deletion
      constructs of the 15-PGDH promoter, we have found that E-twenty six (Ets) is the
      most essential determinant for 15-PGDH induction. 15 d-PGJ2 induced
      phosphorylation of Elk-1, one of Ets transcription factor family members, in the
      nucleus. Knockdown of Elk-1 abolished the ability of 15 d-PGJ2 to upregulate 15
      PGDH expression. Furthermore, 15 d-PGJ2-mediated activation of Elk-1 was found to
      be dependent on activation of extracellular-signal related kinase (ERK) 1/2.
      Treatment of U0126, a pharmacological inhibitor of MEK1/2-ERK, abolished
      phosphorylation and DNA binding of Elk-1 as well as 15-PGDH induction in 15 d
      PGJ2-treated MDA-MB-231 cells. Moreover, 15 d-PGJ2 generated reactive oxygen
      species (ROS), which contribute to the expression of 15-PGDH as well as
      phosphorylation of ERK1/2 and Elk-1. 15 d-PGJ2 inhibited the migration of MDA-MB
      231 cells, which was attenuated by transient transfection with 15-PGDH siRNA.
      Taken together, these findings suggest that 15 d-PGJ2 induces the expression of
      15-PGDH through ROS-mediated activation of ERK1/2 and subsequently Elk-1 in the
      MDA-MB-231 cells, which may contribute to tumor suppressive activity of this
      cyclopentenone prostaglandin.

PMID- 25773925
TI  - Transvaginal genital fistula repair with insertion of Foley catheter via fistula
      tract.
AB  - AIM: Genital fistula is one of the most devastating injuries in women. Despite
      advances in medical care, it continues to be a distressing problem, and the
      success rate of repair surgery is still limited. We herein describe our
      experience with the surgical approach using Foley catheter to repair genital
      fistula after gynecological surgery. METHODS: We retrospectively reviewed 29
      patients who had received genital fistula repair surgery with Foley catheter
      between October 2011 and December 2013. Based on traditional transvaginal genital
      fistula repair surgery, we inserted a Foley catheter into the bladder or
      intestine through the fistula opening. As a result, the fistula opening could be
      tracked, which allows for a clear view to improve fistula repair. All 29 patients
      were followed up at 1, 4, and 12 weeks postoperatively. RESULTS: Of the 29
      patients, 28 had successful surgical outcome (96.55% success rate). The mean
      operative time was 85 +/- 8.1 min. The mean blood loss was 109 +/- 23.4 mL. No
      intraoperative complications were observed. The mean postoperative
      hospitalization time was 10 +/- 2.8 days. The follow-up rate was 100%.
      CONCLUSIONS: Repair of transvaginal genital fistula using Foley catheter had a
      high success rate, short operative time, minimal blood loss, low morbidity and
      short hospital stay. Therefore, this approach is minimally invasive and
      effective.

PMID- 25773919
TI  - Outcomes of anatomical versus functional testing for coronary artery disease.
AB  - BACKGROUND: Many patients have symptoms suggestive of coronary artery disease
      (CAD) and are often evaluated with the use of diagnostic testing, although there
      are limited data from randomized trials to guide care. METHODS: We randomly
      assigned 10,003 symptomatic patients to a strategy of initial anatomical testing
      with the use of coronary computed tomographic angiography (CTA) or to functional
      testing (exercise electrocardiography, nuclear stress testing, or stress
      echocardiography). The composite primary end point was death, myocardial
      infarction, hospitalization for unstable angina, or major procedural
      complication. Secondary end points included invasive cardiac catheterization that
      did not show obstructive CAD and radiation exposure. RESULTS: The mean age of the
      patients was 60.8+/-8.3 years, 52.7% were women, and 87.7% had chest pain or
      dyspnea on exertion. The mean pretest likelihood of obstructive CAD was 53.3+/
      21.4%. Over a median follow-up period of 25 months, a primary end-point event
      occurred in 164 of 4996 patients in the CTA group (3.3%) and in 151 of 5007
      (3.0%) in the functional-testing group (adjusted hazard ratio, 1.04; 95%
      confidence interval, 0.83 to 1.29; P=0.75). CTA was associated with fewer
      catheterizations showing no obstructive CAD than was functional testing (3.4% vs.
      4.3%, P=0.02), although more patients in the CTA group underwent catheterization
      within 90 days after randomization (12.2% vs. 8.1%). The median cumulative
      radiation exposure per patient was lower in the CTA group than in the functional
      testing group (10.0 mSv vs. 11.3 mSv), but 32.6% of the patients in the
      functional-testing group had no exposure, so the overall exposure was higher in
      the CTA group (mean, 12.0 mSv vs. 10.1 mSv; P<0.001). CONCLUSIONS: In symptomatic
      patients with suspected CAD who required noninvasive testing, a strategy of
      initial CTA, as compared with functional testing, did not improve clinical
      outcomes over a median follow-up of 2 years. (Funded by the National Heart, Lung,
      and Blood Institute; PROMISE ClinicalTrials.gov number, NCT01174550.).

PMID- 25773926
TI  - Validation of an acoustic location system to monitor Bornean orangutan (Pongo
      pygmaeus wurmbii) long calls.
AB  - The long call is an important vocal communication signal in the widely dispersed,
      semi-solitary orangutan. Long calls affect individuals' ranging behavior and
      mediate social relationships and regulate encounters between dispersed
      individuals in a dense rainforest. The aim of this study was to test the utility
      of an Acoustic Location System (ALS) for recording and triangulating the loud
      calls of free-living primates. We developed and validated a data extraction
      protocol for an ALS used to record wild orangutan males' long calls at the Tuanan
      field site (Central Kalimantan). We installed an ALS in a grid of 300 ha,
      containing 20 SM2+ recorders placed in a regular lattice at 500 m intervals, to
      monitor the distribution of calling males in the area. The validated system had
      the following main features: (i) a user-trained software algorithm (Song Scope)
      that reliably recognized orangutan long calls from sound files at distances up to
      700 m from the nearest recorder, resulting in a total area of approximately 900
      ha that could be monitored continuously; (ii) acoustic location of calling males
      up to 200 m outside the microphone grid, which meant that within an area of
      approximately 450 ha, call locations could be calculated through triangulation.
      The mean accuracy was 58 m, an error that is modest relative to orangutan
      mobility and average inter-individual distances. We conclude that an ALS is a
      highly effective method for detecting long-distance calls of wild primates and
      triangulating their position. In combination with conventional individual focal
      follow data, an ALS can greatly improve our knowledge of orangutans' social
      organization, and is readily adaptable for studying other highly vocal animals.

PMID- 25773927
TI  - Association between the oxytocin receptor gene polymorphism (rs53576) and bulimia
      nervosa.
AB  - OBJECTIVE: Oxytocin circuits are implicated in the regulation of appetite and
      weight. Variants in the oxytocin receptor (OXTR) gene have been associated with
      bulimic behaviour. This study aimed to investigate the association between the
      OXTR gene and eating disorders. METHOD: We genotyped six single nucleotide
      polymorphisms, rs53576, rs237879, rs2228485, rs13316193, rs2254298 and rs1042778,
      located within the OXTR gene in Korean patients with eating disorders using the
      single-base extension method. We studied a total of 262 women, including 69
      patients with anorexia nervosa, 90 patients with bulimia nervosa (BN), and 103
      healthy women. RESULTS: We found a positive association between the G allele of
      OXTR rs53576 and BN. In the BN group, the G carriers showed a high score on the
      behavioural inhibition system. CONCLUSIONS: These findings suggest the
      involvement of the oxytocinergic system in the mechanism that underlies BN.

PMID- 25773929
TI  - Frequent alterations of HER2 through mutation, amplification, or overexpression
      in pleomorphic lobular carcinoma of the breast.
AB  - Mutations in HER2 gene have been identified in a small subset of breast cancer
      cases. Identification of HER2 mutation has therapeutic implications for breast
      cancer, but whether a subgroup of breast cancer with a higher frequency of HER2
      mutation exists, remains unknown. We analyzed HER2 mutation and pathologic
      factors on 73 formalin-fixed, paraffin-embedded samples, including 21 pleomorphic
      invasive lobular carcinoma (p-ILC) cases, 3 pleomorphic lobular carcinoma in situ
      (p-LCIS) cases, and 49 classic invasive lobular carcinoma (c-ILC) cases.
      Mutations were identified through direct sequencing. HER2 overexpression and
      amplification were determined through immunohistochemistry and fluorescent in
      situ hybridization. Six mutations were identified, including five in the 24 p-ILC
      or p-LCIS (p-ILC/p-LCIS) cases (20.8 %) and one in the 49 c-ILC cases (2.0 %),
      and the difference in frequency was significant (p = 0.013). Eight of the 24
      (33.3 %) p-ILC/p-LCIS cases exhibited HER2 amplification or overexpression
      (amplification/overexpression), which was significantly higher than in the c-ILC
      cases (1/49, 2 %). Mutation and amplification/overexpression were mutually
      exclusive. HER2 mutations were identified more frequently in the p-ILC/p-LCIS
      cases with extensive apocrine change (p = 0.018). Combined HER2 alterations
      through mutation or amplification/overexpression were more frequently identified
      in p-ILC/p-LCIS cases without estrogen receptor expression. The high frequency
      (54.1 %, 13/24) of combined HER2 alterations in the p-ILC/p-LCIS cases suggests a
      crucial role of HER2 in the pathogenesis of p-ILC/p-LCIS. Because of the reported
      responsiveness of HER2 mutation to anti-HER2 therapy, p-ILC patients without HER2
      amplification/overexpression should receive HER2 mutation analysis to identify
      this therapeutically relevant target.

PMID- 25773928
TI  - Integrated analysis of DNA methylation, immunohistochemistry and mRNA expression,
      data identifies a methylation expression index (MEI) robustly associated with
      survival of ER-positive breast cancer patients.
AB  - Identification of prognostic gene expression signatures may enable improved
      decisions about management of breast cancer. To identify a prognostic signature
      for breast cancer, we performed DNA methylation profiling and identified
      methylation markers that were associated with expression of ER, PR, HER2, CK5/6,
      and EGFR proteins. Methylation markers that were correlated with corresponding
      mRNA expression levels were identified using 208 invasive tumors from a
      population-based case-control study conducted in Poland. Using this approach, we
      defined the methylation expression index (MEI) signature that was based on a
      weighted sum of mRNA levels of 57 genes. Classification of cases as low or high
      MEI scores was related to survival using Cox regression models. In the Polish
      study, women with ER-positive low MEI cancers had reduced survival at a median of
      5.20 years of follow-up, HR = 2.85 95 % CI = 1.25-6.47. Low MEI was also related
      to decreased survival in four independent datasets totaling over 2500 ER-positive
      breast cancers. These results suggest that integrated analysis of tumor
      expression markers, DNA methylation, and mRNA data may be an important approach
      for identifying breast cancer prognostic signatures. Prospective assessment of
      MEI along with other prognostic signatures should be evaluated in future studies.

PMID- 25773930
TI  - Pnck overexpression in HER-2 gene-amplified breast cancer causes Trastuzumab
      resistance through a paradoxical PTEN-mediated process.
AB  - The gene for Pregnancy Up-regulated Non-ubiquitous Calmodulin Kinase (Pnck), a
      novel calmodulin kinase, is expressed in roughly one-third of human breast
      tumors, but not in adjoining normal tissues. Pnck alters EGFR stability and
      function, prompting this study to determine if Pnck expression has implications
      for HER-2 function and HER-2-directed therapy. The frequency of Pnck expression
      in HER-2-amplified breast cancer was examined by immunohistochemistry, and the
      impact of Pnck expression in the presence of HER-2 amplification on cancer cell
      proliferation, clonogenicity, cell-cycle progression, and Trastuzumab sensitivity
      was examined in vitro by transfection of cells with Pnck. Cell signaling was
      probed by Western blot analysis and shRNA-mediated PTEN knockdown. Over 30 % of
      HER-2 amplified tumors were found to express Pnck. Expression of Pnck in SkBr3
      cells resulted in increased proliferation, clonal growth, cell-cycle progression,
      and Trastuzumab resistance. Pnck expression increases Hsp27 expression,
      Trastuzumab partial agonist activity on HER-2 Y1248 phosphorylation, and
      suppressed extracellular signal-regulated kinase (ERK1/2) activity. Knockdown of
      endogenous PTEN upregulated ERK1/2 activity, inhibited cellular proliferation,
      and partially sensitized Pnck/SKBr3 cells to Trastuzumab treatment. Increased
      proliferation of the Pnck/SKBr3 cells was observed following expression of
      protein phosphatase active and lipid phosphatase dead PTEN mutant but not the
      total phosphatase dead PTEN mutant. Co-overexpression of HER-2 and Pnck results
      in enhanced tumor cell proliferation and Trastuzumab resistance that is
      paradoxically dependent on PTEN protein phosphatase activity. This suggests that
      Pnck may be a marker of Trastuzumab resistance and possibly a therapeutic target.

PMID- 25773931
TI  - High prevalence of "Candidatus Rickettsia andeanae" and apparent exclusion of
      Rickettsia parkeri in adult Amblyomma maculatum (Acari: Ixodidae) from Kansas and
      Oklahoma.
AB  - Amblyomma maculatum (the Gulf Coast tick), an aggressive, human-biting, Nearctic
      and Neotropical tick, is the principal vector of Rickettsia parkeri in the United
      States. This pathogenic spotted fever group Rickettsia species has been
      identified in 8-52% of questing adult Gulf Coast ticks in the southeastern United
      States. To our knowledge, R. parkeri has not been reported previously from adult
      specimens of A. maculatum collected in Kansas or Oklahoma. A total of 216 adult
      A. maculatum ticks were collected from 18 counties in Kansas and Oklahoma during
      2011-2014 and evaluated by molecular methods for evidence of infection with R.
      parkeri. No infections with this agent were identified; however, 47% of 94 ticks
      collected from Kansas and 73% of 122 ticks from Oklahoma were infected with
      "Candidatus Rickettsia andeanae" a spotted fever group Rickettsia species of
      undetermined pathogenicity. These preliminary data suggest that "Ca. R. andeanae"
      is well-adapted to survival in populations of A. maculatum in Kansas and
      Oklahoma, and that its ubiquity in Gulf Coast ticks in these states may
      effectively exclude R. parkeri from their shared arthropod host, which could
      diminish markedly or preclude entirely the occurrence of R. parkeri rickettsiosis
      in this region of the United States. 

PMID- 25773932
TI  - Biventricular failure with low pulmonary vascular resistance was managed by left
      ventricular assist device alone without right-sided mechanical support.
AB  - How to manage preoperative right ventricular dysfunction (RVD) in heart failure
      patients without cardiogenic shock remains as a matter to be debated because
      implantable biventricular assist device treatment has not been established thus
      far. We here presented a patient with significant RVD indicated by low RV stroke
      work index (0.3 g/m) and RV dilatation as well as low pulmonary vascular
      resistance (PVR, 0.8 Wood Unit), who was managed by the introduction of
      pimobendan and sildenafil after the implantation of DuraHeart and tricuspid
      annuloplasty without right VAD, although his New York Heart Association symptom
      remained class III. Preoperative low PVR may be a key for successful LVAD
      treatment alone without right VAD in patients with INTERMACS profile 3 suffering
      RVD. 

PMID- 25773933
TI  - Depression and Risk for Diabetes: A Meta-Analysis.
AB  - OBJECTIVE: Many studies have reported the relationship between depression and
      diabetes, but the results have been inconsistent. Our aim was to conduct a
      systematic review through meta-analysis to assess the association of depression
      with the risk for developing diabetes. METHODS: We retrieved the studies
      concerning depression and the risk for diabetes. Meta-analysis was applied to
      calculate the combined effect values and their 95% confidence intervals. The risk
      for publication bias was assessed by the Egger regression asymmetry test.
      RESULTS: As many as 33 articles were included in the meta-analysis, for a total
      of 2 411 641 participants. The pooled relative risk for diabetes was 1.41 (95%
      CI, 1.25-1.59) for depression, and the combined relative risk for type 2 diabetes
      mellitus was 1.32 (95% CI, 1.18-1.47). CONCLUSIONS: Depressed people have a 41%
      increased risk for developing diabetes mellitus and a 32% increased risk for
      developing type 2 diabetes. The mechanisms underlying this relationship are still
      unclear and need further research.

PMID- 25773934
TI  - Cardiovascular disease prediction: do pulmonary disease-related chest CT features
      have added value?
AB  - OBJECTIVE: Certain pulmonary diseases are associated with cardiovascular disease
      (CVD). Therefore we investigated the incremental predictive value of pulmonary,
      mediastinal and pleural features over cardiovascular imaging findings. METHODS: A
      total of 10,410 patients underwent diagnostic chest CT for non-cardiovascular
      indications. Using a case-cohort approach, we visually graded CTs from the cases
      and from an approximately 10 % random sample of the baseline cohort (n = 1,203)
      for cardiovascular, pulmonary, mediastinal and pleural findings. The incremental
      value of pulmonary disease-related CT findings above cardiovascular imaging
      findings in cardiovascular event risk prediction was quantified by comparing
      discrimination and reclassification. RESULTS: During a mean follow-up of 3.7
      years (max. 7.0 years), 1,148 CVD events (cases) were identified. Addition of
      pulmonary, mediastinal and pleural features to a cardiovascular imaging findings
      based prediction model led to marginal improvement of discrimination (increase in
      c-index from 0.72 (95 % CI 0.71-0.74) to 0.74 (95 % CI 0.72-0.75)) and
      reclassification measures (net reclassification index 6.5 % (p < 0.01)).
      CONCLUSION: Pulmonary, mediastinal and pleural features have limited predictive
      value in the identification of subjects at high risk of CVD events beyond
      cardiovascular findings on diagnostic chest CT scans. KEY POINTS: * Incidental
      cardiovascular findings on routine chest CT can predict cardiovascular disease *
      Non-cardiovascular chest CT abnormalities are associated with cardiovascular
      disease * Non-cardiovascular chest CT features have limited predictive value
      beyond cardiovascular features.

PMID- 25773935
TI  - A comparative study for image quality and radiation dose of a cone beam computed
      tomography scanner and a multislice computed tomography scanner for paranasal
      sinus imaging.
AB  - OBJECTIVES: To evaluate image quality and radiation dose of a state of the art
      cone beam computed tomography (CBCT) system and a multislice computed tomography
      (MSCT) system in patients with sinonasal poliposis. METHODS: In this
      retrospective study two radiologists evaluated 57 patients with sinonasal
      poliposis who underwent a CBCT or MSCT sinus examination, along with a control
      group of 90 patients with normal radiological findings. Tissue doses were
      measured using a phantom model with thermoluminescent dosimeters (TLD). RESULTS:
      Overall image quality in CBCT was scored significantly higher than in MSCT in
      patients with normal radiologic findings (p-value: 0.00001). In patients with
      sinonasal poliposis, MSCT scored significantly higher than CBCT (p-value:
      0.00001). The average effective dose for MSCT was 42% higher compared to CBCT
      (108 MUSv vs 63 MUSv). CONCLUSIONS: CBCT and MSCT are both suited for the
      evaluation of sinonasal poliposis. In patients with sinonasal poliposis,
      clinically important structures of the paranasal sinuses can be better delineated
      with MSCT, whereas in patients without sinonasal poliposis, CBCT turns out to
      define the important structures of the sinonasal region better. However, given
      the lower radiation dose, CBCT can be considered for the evaluation of the
      sinonasal structures in patients with sinonasal poliposis. KEY POINTS: * CBCT and
      MSCT are both suited for evaluation of sinonasal poliposis. * Effective dose for
      MSCT was 42% higher compared to CBCT. * In patients with sinonasal poliposis,
      clinically important anatomical structures are better delineated with MSCT. * In
      patients with normal radiological findings, clinically important anatomical
      structures are better delineated with CBCT.

PMID- 25773936
TI  - No increase in Kidney Injury Molecule-1 and Neutrophil Gelatinase-Associated
      Lipocalin excretion following intravenous contrast enhanced-CT.
AB  - OBJECTIVES: To analyze kidney injury molecule-1 (KIM-1) and neutrophil gelatinase
      associated lipocalin (N-GAL) excretion post-intravenous contrast enhanced-CT (CE
      CT) in patients with chronic kidney disease (CKD). METHODS: Patients were
      enrolled in a trial on hydration regimes to prevent contrast-induced acute kidney
      injury (CI-AKI). Blood and urine samples were taken at baseline, 4 - 6, and 48 -
      96 h post CE-CT. Urinary KIM-1 and N-GAL values were normalized for urinary
      creatinine levels, presented as medians with 2.5 - 97.5 percentiles. RESULTS: Of
      the enrolled 511 patients, 10 (2%) were lost to follow-up. CI-AKI occurred in
      3.9% of patients (20/501). Median KIM-1 values were 1.2 (0.1 - 7.7) at baseline,
      1.3 (0.1 - 8.6) at 4 - 6 h, and 1.3 ng/mg (0.1 - 8.1) at 48 - 96 h post CE-CT (P
      = 0.39). Median N-GAL values were 41.0 (4.4 - 3,174.4), 48.9 (5.7 - 3,406.1), and
      37.8 MUg/mg (3.5 - 3,200.4), respectively (P = 0.07). The amount of KIM-1 and N
      GAL excretion in follow-up was similar for patients with and without CI-AKI (P
      value KIM-1 0.08, P-value N-GAL 0.73). Neither patient characteristics at
      baseline including severe CKD, medication use, nor contrast dose were associated
      with increased excretion of KIM-1 or N-GAL during follow-up. CONCLUSION: KIM-1
      and N-GAL excretion were unaffected by CE-CT both in patients with and without CI
      AKI, suggesting that CI-AKI was not accompanied by tubular injury. KEY POINTS: *
      KIM-1 and N-GAL excretion were unaffected by intravenous contrast-enhanced CT (CE
      CT). * Patient or procedure characteristics were not associated with increased
      KIM-1 or N-GAL excretion. * Performance of CE-CT in CKD patients is likely to be
      safe.

PMID- 25773937
TI  - Demonstration of the reproducibility of free-breathing diffusion-weighted MRI and
      dynamic contrast enhanced MRI in children with solid tumours: a pilot study.
AB  - OBJECTIVES: The objectives are to examine the reproducibility of functional MR
      imaging in children with solid tumours using quantitative parameters derived from
      diffusion-weighted (DW-) and dynamic contrast enhanced (DCE-) MRI. METHODS:
      Patients under 16-years-of age with confirmed diagnosis of solid tumours (n = 17)
      underwent free-breathing DW-MRI and DCE-MRI on a 1.5 T system, repeated 24 hours
      later. DW-MRI (6 b-values, 0-1000 sec/mm(2)) enabled monoexponential apparent
      diffusion coefficient estimation using all (ADC0-1000) and only >=100 sec/mm(2)
      (ADC100-1000) b-values. DCE-MRI was used to derive the transfer constant
      (K(trans)), the efflux constant (kep), the extracellular extravascular volume
      (ve), and the plasma fraction (vp), using a study cohort arterial input function
      (AIF) and the extended Tofts model. Initial area under the gadolinium enhancement
      curve and pre-contrast T1 were also calculated. Percentage coefficients of
      variation (CV) of all parameters were calculated. RESULTS: The most reproducible
      cohort parameters were ADC100-1000 (CV = 3.26%), pre-contrast T1 (CV = 6.21%),
      and K(trans) (CV = 15.23%). The ADC100-1000 was more reproducible than ADC0-1000,
      especially extracranially (CV = 2.40% vs. 2.78%). The AIF (n = 9) derived from
      this paediatric population exhibited sharper and earlier first-pass and
      recirculation peaks compared with the literature's adult population average.
      CONCLUSIONS: Free-breathing functional imaging protocols including DW-MRI and DCE
      MRI are well-tolerated in children aged 6 - 15 with good to moderate measurement
      reproducibility. KEY POINTS: * Diffusion MRI protocol is feasible and well
      tolerated in a paediatric oncology population. * DCE-MRI for pharmacokinetic
      evaluation is feasible and well tolerated in a paediatric oncology population. *
      Paediatric arterial input function (AIF) shows systematic differences from the
      adult population-average AIF. * Variation of quantitative parameters from paired
      functional MRI measurements were within 20%.

PMID- 25773938
TI  - Nosocomial rapidly growing mycobacterial infections following laparoscopic
      surgery: CT imaging findings.
AB  - OBJECTIVE: To identify the distribution and frequency of computed tomography (CT)
      findings in patients with nosocomial rapidly growing mycobacterial (RGM)
      infection after laparoscopic surgery. METHOD: A descriptive retrospective study
      in patients with RGM infection after laparoscopic surgery who underwent CT
      imaging prior to initiation of therapy. The images were analyzed by two
      radiologists in consensus, who evaluated the skin/subcutaneous tissues, the
      abdominal wall, and intraperitoneal region separately. The patterns of
      involvement were tabulated as: densification, collections, nodules (>=1.0 cm),
      small nodules (<1.0 cm), pseudocavitated nodules, and small pseudocavitated
      nodules. RESULTS: Twenty-six patients met the established criteria. The
      subcutaneous findings were: densification (88.5%), small nodules (61.5%), small
      pseudocavitated nodules (23.1 %), nodules (38.5%), pseudocavitated nodules
      (15.4%), and collections (26.9%). The findings in the abdominal wall were:
      densification (61.5%), pseudocavitated nodules (3.8%), and collections (15.4%).
      The intraperitoneal findings were: densification (46.1%), small nodules (42.3%),
      nodules (15.4%), and collections (11.5%). CONCLUSION: Subcutaneous CT findings in
      descending order of frequency were: densification, small nodules, nodules, small
      pseudocavitated nodules, pseudocavitated nodules, and collections. The musculo
      fascial plane CT findings were: densification, collections, and pseudocavitated
      nodules. The intraperitoneal CT findings were: densification, small nodules,
      nodules, and collections. KEY POINTS: * Rapidly growing mycobacterial infection
      may occur following laparoscopy. * Post-laparoscopy mycobacterial infection CT
      findings are densification, collection, and nodules. * Rapidly growing
      mycobacterial infection following laparoscopy may involve the peritoneal cavity.
      * Post-laparoscopy rapidly growing mycobacterial intraperitoneal infection is not
      associated with ascites or lymphadenopathy.

PMID- 25773939
TI  - CT-guided localization of small pulmonary nodules using adjacent microcoil
      implantation prior to video-assisted thoracoscopic surgical resection.
AB  - OBJECTIVES: To describe and assess the localization of small peripheral pulmonary
      nodules prior to video-assisted thoracoscopic surgical (VATS) resection using the
      implantation of microcoils. METHODS: Ninety-two patients with 101 pulmonary
      nodules underwent computed tomography (CT)-guided implantation of microcoils
      proximal to each nodule. Patients were randomly assigned to undergo entire
      microcoil or leaving-microcoil-end implantations. The complications and efficacy
      of the two implantation methods were evaluated. VATS resection of lung tissue
      containing each pulmonary lesion and microcoil were performed in the direction of
      the microcoil marker. Histopathological analysis was performed for the resected
      pulmonary lesions. RESULTS: CT-guided microcoil implantation was successful in
      99/101 cases, and the placement of microcoils within 1 cm of the nodules was not
      disruptive. There was no difference in the complications and efficacy associated
      with the entire implantation method (performed for 51/99 nodules) versus the
      leaving-microcoil-end implantation method (performed for 48/99 nodules). All
      nodules were successfully removed using VATS resection. Asymptomatic pneumothorax
      occurred in 16 patients and mild pulmonary haemorrhage occurred in nine patients.
      However, none of these patients required further surgical treatment. CONCLUSIONS:
      Preoperative localization of small pulmonary nodules using a refined percutaneous
      microcoil implantation method was found to be safe and useful prior to VATS
      resection. KEY POINTS: * An increasing number of small, indeterminate pulmonary
      lesions need to be characterized. * Entire microcoil and leaving-microcoil-end
      implantation methods were described for nodule localization. * Adjacent microcoil
      localization prior to video-assisted thoracoscopic surgical resection involved
      minimal intervention. * Preoperative microcoil localization facilitates the
      definitive resection of small pulmonary nodules.

PMID- 25773940
TI  - Computed tomography of acute pulmonary embolism: state-of-the-art.
AB  - Multidetector computed tomography (CT) plays an important role in the detection,
      risk stratification and prognosis evaluation of acute pulmonary embolism. This
      review will discuss the technical improvements for imaging peripheral pulmonary
      arteries, the methods of assessing pulmonary embolism severity based on CT
      findings, a multidetector CT technique for pulmonary embolism detection, and
      lastly, how to avoid overutilization of CT pulmonary angiography and
      overdiagnosis of pulmonary embolism. Key Points * We describe clinical prediction
      rules and D-dimers for pulmonary embolism evaluation. * Overutilization of CT
      pulmonary angiography and overdiagnosis of pulmonary embolism should be avoided.
      * We discuss technical improvements for imaging peripheral pulmonary arteries. *
      Pulmonary embolism severity can be assessed based on CT findings. * We discuss
      multidetector CT techniques for pulmonary embolism detection. 

PMID- 25773941
TI  - Noninvasive diagnosis of hepatocellular carcinoma on gadoxetic acid-enhanced MRI:
      can hypointensity on the hepatobiliary phase be used as an alternative to
      washout?
AB  - OBJECTIVES: To determine which dynamic phase(s) of gadoxetic acid-enhanced MRI is
      most appropriate to assess "washout" in the noninvasive diagnosis of
      hepatocellular carcinoma (HCC) based on hemodynamic pattern. METHODS: In this
      retrospective cohort study, 288 consecutive patients with chronic liver disease
      presented with 387 arterially enhancing nodules (292 HCCs, 95 non-HCCs) (>=1 cm)
      on gadoxetic acid-enhanced MRI. All HCCs were confirmed by histopathology or by
      their typical enhancement pattern on dynamic liver CT. MR imaging diagnosis of
      HCC was made using criteria of arterial enhancement and hypointensity relative to
      the surrounding parenchyma (1) on the portal-venous phase (PVP), (2) on the PVP
      and/or transitional phase (TP), or (3) on the PVP and/or TP, and/or hepatobiliary
      phase (HBP). RESULTS: For the noninvasive diagnosis of HCC, criterion 1 provided
      significantly higher specificity (97.9%; 95% confidence interval, 92.6 - 99.7%)
      than criteria 2 (86.3%; 77.7 - 92.5%), or 3 (48.4%; 38.0 - 58.9%). Conversely,
      higher sensitivity was obtained with criterion 3 (93.8%; 90.4 - 96.3%) than with
      criterion 2 (86.6%; 82.2 - 90.3%) or 1 (70.9%; 65.3 - 76.0%). CONCLUSIONS: To
      make a sufficiently specific diagnosis of HCC using gadoxetic acid-enhanced MRI
      based on typical enhancement features, washout should be determined on the PVP
      alone rather than combined with hypointensity on the TP or HBP. KEY POINTS: *
      Gadoxetic acid-enhanced MRI enhancement features can be used to diagnose HCC. *
      Washout should be determined on the PVP alone for high specificity. *
      Hypointensity on the TP or HBP increases sensitivity but lowers specificity.

PMID- 25773942
TI  - MRI findings of serous atrophy of bone marrow and associated complications.
AB  - OBJECTIVES: To report the MRI appearance of serous atrophy of bone marrow (SABM)
      and analyse clinical findings and complications of SABM. METHODS: A retrospective
      search of MRI examinations of SABM was performed. Symptoms, underlying
      conditions, MRI findings, delay in diagnosis and associated complications were
      recorded. RESULTS: We identified 30 patients (15 male, 15 female; mean age: 46 +/
      21 years) with MRI findings of SABM. Underlying conditions included anorexia
      nervosa (n = 10), cachexia from malignant (n = 5) and non-malignant (n = 7)
      causes, massive weight loss after bariatric surgery (n = 1), biliary atresia (n =
      1), AIDS (n = 3), endocrine disorders (n = 2) and scurvy (n = 1). MRI showed
      mildly hypointense signal on T1- weighted and hyperintense signal on fat
      suppressed fluid-sensitive images of affected bone marrow in all cases and
      similar signal abnormalities of the adjacent subcutaneous fat in 29/30 cases.
      Seven patients underwent repeat MRI due to initial misinterpretation of bone
      marrow signal as technical error. Superimposed fractures of the hips and lower
      extremities were common (n = 14). CONCLUSIONS: SABM occurs most commonly in
      anorexia nervosa and cachexia. MRI findings of SABM are often misinterpreted as
      technical error requiring unnecessary repeat imaging. SABM is frequently
      associated with fractures of the lower extremities. KEY POINTS: * SABM occurs in
      several underlying conditions, most commonly anorexia nervosa and cachexia. *
      Abnormal marrow signal is often misinterpreted as technical error requiring
      unnecessary repeat imaging. * SABM is frequently associated with stress
      fractures. * Fractures in SABM can be obscured by marrow signal abnormality on
      MRI.

PMID- 25773943
TI  - Virtual iron concentration imaging based on dual-energy CT for noninvasive
      quantification and grading of liver iron content: An iron overload rabbit model
      study.
AB  - OBJECTIVES: To assess the accuracy of liver iron content (LIC) quantification and
      grading ability associated with clinical LIC stratification using virtual iron
      concentration (VIC) imaging on dual-energy CT (DECT) in an iron overload rabbit
      model. METHODS: Fifty-one rabbits were prepared as iron-loaded models by
      intravenous injection of iron dextran. DECT was performed at 80 and 140 kVp. VIC
      images were derived from an iron-specific algorithm. Postmortem LIC assessments
      were conducted on an inductively coupled plasma (ICP) spectrometer. Correlation
      between VIC and LIC was analyzed. VIC were stratified according to the
      corresponding clinical LIC thresholds of 1.8, 3.2, 7.0, and 15.0 mg Fe/g.
      Diagnostic performance of stratification was evaluated by receiver operating
      characteristic analysis. RESULTS: VIC linearly correlated with LIC (r = 0.977, P
      < 0.01). No significant difference was observed between VIC-derived LICs and ICP
      (P > 0.05). For the four clinical LIC thresholds, the corresponding cutoff values
      of VIC were 19.6, 25.3, 36.9, and 61.5 HU, respectively. The highest sensitivity
      (100%) and specificity (100 %) were achieved at the threshold of 15.0 mg Fe/g.
      CONCLUSIONS: Virtual iron concentration imaging on DECT showed potential ability
      to accurately quantify and stratify hepatic iron accumulation in the iron
      overload rabbit model. KEY POINTS: * Virtual iron concentration (VIC) linearly
      correlates with liver iron content (LIC). * VIC accurately quantifies LIC. * VIC
      accurately grades LIC based on clinical LIC stratification.

PMID- 25773944
TI  - Potential clinical utility of ultrasensitive circulating tumor DNA detection with
      CAPP-Seq.
AB  - Tumors continually shed DNA into the circulation, where it can be noninvasively
      accessed. The ability to accurately detect circulating tumor DNA (ctDNA) could
      significantly impact the management of patients with nearly every cancer type.
      Quantitation of ctDNA could allow objective response assessment, detection of
      minimal residual disease and noninvasive tumor genotyping. The latter application
      overcomes the barriers currently limiting repeated tumor tissue sampling during
      therapy. Recent technical advancements have improved upon the sensitivity,
      specificity and feasibility of ctDNA detection and promise to enable innovative
      clinical applications. Here, we focus on the potential clinical utility of ctDNA
      analysis using CAncer Personalized Profiling by deep Sequencing (CAPP-Seq), a
      novel next-generation sequencing-based approach for ultrasensitive ctDNA
      detection. Applications of CAPP-Seq for the personalization of cancer detection
      and therapy are discussed. 

PMID- 25773945
TI  - Alterations in cancer cell metabolism: the Warburg effect and metabolic
      adaptation.
AB  - The Warburg effect means higher glucose uptake of cancer cells compared to normal
      tissues, whereas a smaller fraction of this glucose is employed for oxidative
      phosphorylation. With the advent of high throughput technologies and
      computational systems biology, cancer cell metabolism has been reinvestigated
      over the last decades toward identifying various events underlying "how" and
      "why" a cancer cell employs aerobic glycolysis. Significant progress has been
      shaped to revise the Warburg effect. In this study, we have integrated the gene
      expression of 13 different cancer cells with the genome-scale metabolic network
      of human (Recon1) based on the E-Flux method, and analyzed them based on
      constraint-based modeling. Results show that regardless of significant up- and
      down-regulated metabolic genes, the distribution of metabolic changes is similar
      in different cancer types. These findings support the theory that the Warburg
      effect is a consequence of metabolic adaptation in cancer cells.

PMID- 25773946
TI  - Neutrophil-to-lymphocyte ratio in inflammatory bowel disease - as a new predictor
      of disease severity.
AB  - BACKGROUND: The aims of this study were to investigate the utility of neutrophil
      to-lymphocyte ratio (NLR) as a simple and readily available predictor for
      clinical disease activity in inflammatory bowel disease (IBD). METHODS: Sixty-six
      patients (22 CD, 44 UC) and 41 healthy controls were enrolled in the study.
      Erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) levels and
      complete blood count (CBC) were measured. The neutrophil and lymphocyte counts
      were recorded and NLR was calculated. The patients with active or inactive UC and
      CD were classified according to the severity of the disease. RESULT: The serum
      NLR values of active CD patients were significantly higher than those of inactive
      ones and controls (p = 0.000, p = 0.000, respectively). NLR values of active UC
      patients were significantly higher than those of inactive ones and controls (p =
      0.000, p = 0.000, respectively. The optimum NLR cut-off point for active CD and
      UC was 3.2 and 3.1. CONCLUSION: This study demonstrates that NLR in subjects with
      IBD is strongly associated with active disease and correlated with clinical and
      laboratory indices (Tab. 5, Fig. 2, Ref. 31).

PMID- 25773947
TI  - Long term experience of patients with unresectable or metastatic KIT positive
      gastrointestinal stromal tumours.
AB  - A retrospective analysis of consecutive patients (183 in total, of which 105 were
      males and 78 females) with gastrointestinal stromal tumour (GIST) was performed.
      The mean age was 61 years, median age 64 years. The most frequent localization of
      the tumour was stomach in 74 patients (40.4 %) and the small intestine in 46
      patients (25.1 %). Two or more different synchronous or metachronous cancers
      occurred in 34 (18.6 %) patients with histologically confirmed GIST. Ninety-six
      patients were treated with imatinib mesylate in palliative setting during the
      course of their disease. The therapy was finished in 60 patients and 36 patients
      have been treated so far. The median progression-free survival reached 32.9
      months in the group of 96 patients treated with imatinib. The median overall
      survival in the group of 96 patients treated for metastatic disease reached 77
      months. Two-year and 5-year survival was 85.2 % and 63.1 %, respectively. The
      second-line therapy with sunitinib malate was administered in 37 patients, of
      which 31 finished and 6 continued in the therapy. The median progression free
      survival and median survival since the sunitinib therapy initiation reached 8.4
      and 22.1 months, respectively (Tab. 2, Fig. 2, Ref. 16). 

PMID- 25773948
TI  - Reliability of the cervical vertebrae maturation (CVM) method.
AB  - OBJECTIVE: To assess the reliability of the cervical vertebrae maturation method
      (CVM). BACKGROUND: Skeletal maturity estimation can influence the manner and time
      of orthodontic treatment. The CVM method evaluates skeletal growth on the basis
      of the changes in the morphology of cervical vertebrae C2, C3, C4 during growth.
      These vertebrae are visible on a lateral cephalogram, so the method does not
      require an additional radiograph. METHODS: In this website based study, 10
      orthodontists with a long clinical practice (3 routinely using the method -
      "Routine user - RU" and 7 with less experience in the CVM method - "Non-Routine
      user - nonRU") rated twice cervical vertebrae maturation with the CVM method on
      50 cropped scans of lateral cephalograms of children in circumpubertal age (for
      boys: 11.5 to 15.5 years; for girls: 10 to 14 years). Kappa statistics (with
      lower limits of 95% confidence intervals (CI)) and proportion of complete
      agreement on staging was used to evaluate intra- and inter-assessor agreement.
      RESULTS: The mean weighted kappa for intra-assessor agreement was 0.44 (range:
      0.30-0.64; range of lower limits of 95% CI: 0.12-0.48) and for inter-assessor
      agreement was 0.28 (range: -0.01-0.58; range of lower limits of 95% CI: -0.14
      0.42). The mean proportion of identical scores assigned by the same assessor was
      55.2 %(range: 44-74 %) and for different pairs of assessors was 42 % (range: 16
      68 %). CONCLUSIONS: The reliability of the CVM method is questionable and if
      orthodontic treatment should be initiated relative to the maximum growth, the use
      of additional biologic indicators should be considered (Tab. 4, Fig. 1, Ref. 24).

PMID- 25773949
TI  - Crosstalk between possible cytostatic and antiinflammatory potential of
      ketoprofen in the treatment of culture of colon and cervix cancer cell lines.
AB  - OBJECTIVES: The aim of this study was to test the cytostatic potential of
      ketoprofen in the in vitro treatment of cells derived from colon and cervix
      cancer. BACKGROUND: NF-kappaB and cyclooxygenase can have a role in different
      stages of the development and progression of cancer. In recent years, special
      attention has been paid to the possible cytostatic potential of nonsteroidal anti
      inflammatory drugs. There are no published data on the use of ketoprofen in
      pharmacotherapy of the colon and cervical carcinoma. METHODS: We examined the
      effect of ketoprofen alone or in combination with cisplatin and 5-fluorouracil on
      proliferation of the two cell lines, HeLa (human cervical carcinoma cells) and
      Caco-2 (human colon cancer cells) by MTT test. Measurement of the level of NF
      kappaB was also performed in the cells of both cell lines. RESULTS: The results
      of present study have shown that at least one of the mechanisms of
      antiproliferating and/or cytostatic effects of different concentrations of
      ketoprofen on Caco-2 and HeLa cells could include the transcription factor NF
      kappaB. CONCLUSIONS: Since this transcription factor is controlled by the altered
      expression of COX-2, the inhibition of this enzyme by ketoprofen may represent a
      significant step in synergistic cascade of the therapy and prevention of colon
      and cervical cancer (Tab. 4, Ref. 31).

PMID- 25773950
TI  - Selenium prevents lipid peroxidation in liver and lung tissues of rats in acute
      swimming exercise.
AB  - BACKGROUND: Selenium, which is critical for human health, is necessary for
      various metabolic processes, including thyroid hormone metabolism, protection
      against oxidative stress, and immune function. OBJECTIVE: The present study aims
      to examine how selenium administration affects lipid peroxidation in liver and
      lung tissues of rats subjected to acute swimming exercise. METHODS: The study
      included 32 Spraque-Dawley adult male rats divided into Group 1 (general
      control), Group 2 (selenium-administered), Group 3 (swimming), and Group 4
      (selenium-administered swimming). MDA and GSH levels were determined in liver and
      lung tissues. RESULTS: The highest MDA values in the liver and lung tissues were
      found in group 3 in the study. MDA value in group 4 was higher than those in
      groups 1 and 2. Group 4 had the highest liver and lung GSH levels. GSH levels in
      Group 3 were higher than those in groups 1 and 2. CONCLUSION: Results of the
      study indicate that acute swimming exercise causes lipid peroxidation in liver
      and lung tissues, while selenium administration prevents free radical formation
      by increasing antioxidant activity (Tab. 2, Ref. 26).

PMID- 25773951
TI  - Omega-3 fatty acids may be harmful to thickness of aortic intima-media.
AB  - There are several studies confirming an association between nicotine exposure and
      increase in aortic intima-media thickness (aIMT) as a pre-atherosclerotic lesion.
      The omega-3 FAs are on the other hand reported to have an anti-atherogenic
      effect. We aimed to evaluate histopathologically the effect of nicotine exposure
      during pregnancy and lactation period on fetal growth and aIMT at postnatal 45
      days of age in rat pups living in the same conditions and to determine the
      protective effect of omega-3 FAs. Pregnant rats were assigned into four groups.
      In nicotine (N) group; pregnant rats received nicotine subcutaneously and extra
      virgin olive oil by gavage during pregnancy from 1 to 21 days of gestation and
      lactation. In nicotine+ omega-3 FAs (N+O) group; nicotine was administered
      subcutaneously and omega-3 FAs by gavage, in omega-3(O) group; omega-3 FAs were
      administered by gavage and saline subcutaneously, in control(C) group; saline was
      administered subcutaneously and extra-virgin olive oil by gavage for the same
      period.The aIMT was found to be greatest in N+O group, which indicated a
      significant difference compared to the control group (p < 0.05). No statistically
      significant difference was found among other groups.Although the majority of
      studies on omega-3 FAs suggest a beneficial effect, our study showed that
      exposure to omega-3 FAs increased the aIMT (Tab. 2, Fig. 3, Ref. 25). 

PMID- 25773952
TI  - The histopathological effects of levosimendan on liver injury induced by
      myocardial ischemia and reperfusion.
AB  - BACKGROUND: The aim of this study was to evaluate the histological and
      immunohistochemical effects of levosimendan on liver injury induced by myocardial
      ischemia and reperfusion (I/R) in a rat model. METHODS: Twenty-four male Wistar
      Albino rats were randomly divided into the four groups: Group C (Control, n = 6),
      Group I/R (n = 6), Group BI (I/R group treated with levosimendan before ischemia,
      n = 6), and Group AI (I/R group treated with levosimendan after ischemia, n = 6).
      Myocardial I/R was induced by ligation of the left anterior descending coronary
      artery for 30 min followed by two hours of reperfusion in I/R and
      I/R+Levosimendan groups. At the end of the study, liver tissue samples were
      obtained for histopathological and immunohistochemical examination. RESULTS:
      Masson Trichrome staining revealed significant hepatocyte degeneration and
      necrosis most marked in portal acinus Zone 3, especially around the central veins
      in Group I/R. Histopathological changes in Group AI were more similar to the
      changes in Group I/R. Milder hepatocellular degeneration was found in Group BI,
      when compared to groups I/R and AI. Immunohistochemical score was found to be
      significantly higher in Group I/R compared to groups C, BI and AI (p < 0.0001).
      The scores in groups BI and AI were found to be similar (p = 0.068). CONCLUSION:
      Levosimendan ameliorates liver injury induced by myocardial IR, especially when
      administered before induction of ischemia (Fig. 9, Ref. 37).

PMID- 25773953
TI  - Gamma-secretase inhibitor does not modulate angiogenesis in colon adenocarcinoma
      in obese mice.
AB  - BACKGROUND: Notch is a signaling molecule which plays a role in angiogenesis and
      gamma-secretase is required for processing of Notch. In this study, we
      investigated the effect of gamma-secretase inhibitor (DAPT) on tumor angiogenesis
      in diet-induced obese mice. METHODS: 18 mice were divided into three groups;
      control, obese (diet-induced) and obese+DAPT. After 15 weeks, the obese mice were
      subjected for tumor induction of CT26 colon adenocarcinoma cells (5 x 105 cells).
      When the tumor size reached approximately 350 +/- 50 mm3, half of the obese
      animals received DAPT (10mg/kg/day) subcutaneously. Blood samples were taken
      after 14 days and the tumors harvested for immunohistochemical staining and
      capillary density were reported as CD31 positive cells/mm2. RESULTS: The obese
      animals had higher serum leptin and NO concentrations, while, serum VEGF and
      VEGFR-1 concentrations were not different compare to control group.
      Administration of DAPT in obese mice significantly reduced serum VEGFR-1 and
      leptin concentrations and increased serum NO level (p < 0.05). Capillary density
      in the tumors of obese animals was not different compare to control groups. DAPT
      administration could not alter capillary density in the tumors. CONCLUSION:
      Administration of DAPT in obese mice altered serum angiogenic factors, however,
      it could not modulate tumor angiogenesis in diet-induced obese mice (Fig. 4, Ref.
      26).

PMID- 25773954
TI  - The protective effect of N-acetylcysteine against acrylamide toxicity in liver
      and small and large intestine tissues.
AB  - The aim of this study was to investigate the protective effects of N
      acetylcysteine against acrylamide toxicity in liver and small and large intestine
      tissues in rats.The rats were divided into four groups. Acrylamide administration
      increased MDA levels in all tissues significantly (p < 0.05). But acrylamide+NAC
      administration decreased MDA levels significantly as compared to the acrylamide
      group, and lowered it to a level close to the control group values (p < 0.05).
      GSH levels in liver and small intestine tissues reduced significantly in the
      acrylamide group (p < 0.05). But acrylamide+NAC administration increased GSH
      levels significantly in all tissues. Whereas GST activity decreased significantly
      in the acrylamide group in liver and small intestine tissues as compared to the
      other groups (p < 0.05), the GST activity increased significantly in the
      acrylamide+NAC group in all tissues as compared to the acrylamide group (p <
      0.05). Liver histopathology showed that the liver epithelial cells were damaged
      significantly in the acrylamide group. Small intestine histopathology showed that
      the intestinal villous epithelial cells were damaged significantly in the
      acrylamide group.Our results indicate that a high level of acrylamide causes
      oxidative damage in liver and small and large intestine tissues, while N
      acetylcysteine administration in a pharmacological dose shows to have an
      antioxidant effect in preventing this damage (Tab. 2, Fig. 2, Ref. 66). 

PMID- 25773955
TI  - Topiramate has protective effect on renal injury.
AB  - BACKGROUND: Topiramate (TPM) decreases tumor necrosis factor-alpha (TNF-alpha)
      and oxidative stress. We investigated protective effects of TPM on cell damage in
      kidney tissue during ischemia-reperfusion (I/R) damage. METHODS: A total of 30
      male Wistar albino rats were divided into three groups: control, I/R, and I/R
      plus TPM (I/R+TPM). Laparotomy without I/R injury was performed in control group.
      After laparotomy, cross ligation of infrarenal abdominal aorta was applied for
      two hours in I/R groups which was followed by two hours of reperfusion. TPM (100
      mg/kg/day) was orally administrated to animals in the I/R+TPM group for seven
      consecutive days before I/R. RESULTS: The I/R group's TNF-alpha and interleukin-1
      beta (IL-1beta) levels were significantly higher (1184.2 +/- 129.1 pg/mg protein;
      413.1 +/- 28.8 pg/mg protein, respectively) than those of the control (907.8 +/-
      113.0 pg/mg protein, p = 0.002; 374.7 +/- 23.7 pg/mg protein, p = 0.010,
      respectively) and I/R+TPM groups (999.5 +/- 115.2 pg/mg protein, p < 0.001; 377.9
      +/- 30.9 pg/mg protein, p = 0.007, respectively). CONCLUSION: TPM may partially
      prevent renal damage in rats. The opening of new horizons of this kind of
      knowledge will help understand the complex challenge in the prevention of renal
      I/R damage (Tab. 1, Fig. 3, Ref. 42).

PMID- 25773956
TI  - Effects of Nigella sativa on heat-induced testis damage in mouse.
AB  - BACKGROUND: Infertility is one of the major health problems. OBJECTIVES: The aim
      of this study was to evaluate the effects of Nigella sativa on heat-induced
      testicular damage. METHODS: Forty male mice were randomly divided into the four
      equal groups as Control, Heat stressed and, Heated and treated with Nigella
      sativa 10 % and 20 % in diet. The scrotum of mice except to the control mice were
      immersed for 15 min in a water bath at 43  degrees C. Animals in the control
      group were treated identically except that the water bath was maintained at 23 
      degrees C. Fifty days after the heating, blood samples were collected for
      testosterone levels. Testes were removed for the measurement of seminiferous
      tubules diameter and percentage of spermatogenesis and oxidant/antioxidant
      status. RESULTS: Heating stress significantly reduced blood testosterone level
      and increased lipid peroxidation product and decreased antioxidant activities of
      superoxide dismutase, catalase and glutathione peroxidase (p < 0.01). Nigella
      sativa treatment significantly increased blood testosterone level and decreased
      testis malondialdehyde level and increased antioxidant enzymes activities (p <
      0.05). In the mice treated with Nigella sativa, testes illustrated normal
      spermatogenesis and structure. CONCLUSION: The results indicated that
      supplementation of Nigella sativa in diet improves spermatogenesis and
      antioxidant status after a short exposure of the mouse testis to heat (Tab. 1,
      Fig. 4, Ref. 45).

PMID- 25773957
TI  - Candesartan mediates microcirculation in acute necrotizing pancreatitis.
AB  - AIM: In the present study we aimed to determine the effect of an AT-II antagonist
      candesartan on pancreatic microcirculation in an experimental model of acute
      necrotizing pancreatitis. MATERIALS AND METHODS: There were five study groups
      with 10 animals in each. Pancreatitis was induced by intravenous infusion of
      cerulein and coadministration of glycodeoxycholate into biliopancreatic canal.
      Candesartan is given at 6th and 18th hour to the 24th and 48th hour groups,
      respectively. At 24th and 48th hours; following anaesthesia laparotomy was
      performed and laser Doppler flowmetry was performed in the pancreatic tissue of
      the animals. Following scarification blood samples were obtained for amylase,
      myeloperoxidase, IL-6 and tumour necrosis factor alpha. Tissue samples from the
      pancreas were obtained for histopathological analysis, endothelial cell apoptosis
      (TUNEL assay) and matrix metalloproteinase-9 immunohistochemistry. RESULTS:
      Pancreatic microcirculation was higher in the candesartan treated groups (p <
      0.05). Myeloperoxidase, IL-6 and tumour necrosis factor alpha was found to be
      lower in the candesartan treated groups (p < 0.05). The pancreatic edema and
      inflammation were found to be reduced in the candesartan treated groups (p <
      0.05). Endothelial apoptosis was found to be reduced by cadesartan treatment but
      it did not reach statistical significance (p > 0.05). Tissue matrix
      metalloproteinase -9 levels were found to be reduced with candesartan treatment
      (p < 0.05). CONCLUSION: Treatment with candesartan in the early phases of acute
      necrotizing pancreatitis effective on microcirculation of pancreatic tissue (Tab.
      3, Fig. 6, Ref. 28).

PMID- 25773958
TI  - Chorionic morphine, naltrexone and pentoxifylline effect on hypophyso-gonadal
      hormones of male rats.
AB  - BACKGROUND: Knowledge about harmful effects of morphine on hormone secretion
      seems to be necessary. The aim of the present study was to evaluate the effect of
      pentoxifylline on side effects derived by morphine on hypophyso-gonadal hormones
      of male rats. METHODS: 32 male rats were divided into the 4 groups of OSS:
      control (received 40 g Sucrose/l drinking water and intraperitoneal injection of
      1 l/kg normal saline), OMS: morphine group (received 0.4 mg/l + 40 g Sucrose/l in
      drinking water and intraperitoneal injection of 1 l/kg normal saline), NMS:
      morphine+naltrexane group (received 0.4 mg/l + 40 g Sucrose/l in drinking water
      and IP injection dose of 10 mg/kg/ml/day Naltrexane) and PMS: morphine +
      pentoxifylline group (received 0.4 mg/dl + 40 g Sucrose/l in drinking water and
      IP injection dose of 12 mg/kg/ml/day Pentoxifylline) for 56 days, respectively.
      RESULTS: Serum levels of testosterone, LH, FSH hormones were measured.
      Pentoxifylline increased serum levels of testosterone, LH, FSH hormones compared
      to control, morphine and morphine-naltrexane groups. CONCLUSION: Pentoxifylline
      has a significant efficacy for increasing serum levels of sexual hormones.
      Considering that Pentoxifylline is safe and cheap, with easy application, we
      suggest for the usage of this drug for improving semen parameter's quality before
      performing ART for the treatment of morphine addicts (Fig. 1, Ref. 31).

PMID- 25773959
TI  - Complex interplay between the length and composition of the huntingtin-derived
      peptides modulates the intracellular behavior of the N-terminal fragments of
      mutant huntingtin.
AB  - Diverse subcellular localizations of the huntingtin-containing inclusion bodies
      are frequently suspected of reflecting crucial divisions between different
      cellular pathways contributing to the pathophysiology of Huntington's disease.
      Here, we use a panel of different N-terminal huntingtin fragments overexpressed
      in transfected neuronal and non-neuronal cells to demonstrate that it is the
      length of the N-terminal huntingtin fragments rather than a presence of any
      specific amino acid sequences that determines the ratio between the nuclear and
      cytoplasmic inclusion bodies. Importantly, the length of those fragments does
      also seem to strongly influence the folding of the aggregating huntingtin
      species, as indicated by the apparent differences in their accessibility for
      different antibodies directed against particular subdomains within the N-terminal
      part of huntingtin, although these differences do not correlate with the
      peptides' ability to efficiently aggregate within the cell nucleus. Furthermore,
      the relatively long huntingtin fragment containing 588 amino acids of the
      reference sequence shows intracellular behavior that is substantially different
      from that exhibited by its shorter counterparts (containing either 171, 120, 89
      or 64 amino acids), as this rarely aggregating peptide is not only accumulating
      in cytoplasmic inclusions of slightly different morphology but is also most
      strongly affected by the FLAG-tagging procedure that unexpectedly induces (or
      enhances) autophagy-related processes. Together, our results reveal a significant
      heterogeneity of the huntingtin accumulation patterns that are observed at the
      cellular level. These patterns are not only strongly dependent on both the length
      and the amino acid composition of the N-terminal huntingtin peptides but also
      seem to engage different cellular mechanisms implicated in the pathogenesis of
      Huntington's disease, including the non-proteasomal degradation of potentially
      toxic huntingtin forms. 

PMID- 25773960
TI  - Pitfalls in the diagnosis of biallelic PMS2 mutations.
AB  - Constitutional Mismatch Repair Deficiency (CMMR-D) syndrome is an inherited
      childhood cancer syndrome due to bi-allelic mutations in one of the four DNA
      mismatch repair genes involved in Lynch syndrome. The tumor spectrum of this
      syndrome includes hematological, brain and Lynch syndrome associated
      malignancies, with an increased risk of synchronous and metachronous cancers, and
      signs of Neurofibromatosis type-1 syndrome such as cafe-au-lait macules during
      the first three decades of life. Here, we report the first Argentinian patient
      with CMMR-D syndrome, focusing on her history of cancer and gastrointestinal
      manifestations, and the challenging molecular algorithm to finally reach her
      diagnosis. 

PMID- 25773962
TI  - Reversible redox modulation of a lanthanide emissive molecular film.
AB  - Herein we demonstrate redox switchable emission from a sensitised, europium
      ferrocene containing, molecular film assembled by a novel nitrene-based strategy.
      Electrochemical modulation of europium emission upon switching the ferrocene
      moiety's redox state is ascribed to the reversible generation of a quenching
      ferrocenium species. 

PMID- 25773961
TI  - Ketamine as a potential treatment for suicidal ideation: a systematic review of
      the literature.
AB  - OBJECTIVE: To review the published literature on the efficacy of ketamine for the
      treatment of suicidal ideation (SI). METHODS: The PubMed and Cochrane databases
      were searched up to January 2015 for clinical trials and case reports describing
      therapeutic ketamine administration to patients presenting with SI/suicidality.
      Searches were also conducted for relevant background material regarding the
      pharmacological function of ketamine. RESULTS: Nine publications (six studies and
      three case reports) met the search criteria for assessing SI after administration
      of subanesthetic ketamine. There were no studies examining the effect on suicide
      attempts or death by suicide. Each study demonstrated a rapid and clinically
      significant reduction in SI, with results similar to previously described data on
      ketamine and treatment-resistant depression. A total of 137 patients with SI have
      been reported in the literature as receiving therapeutic ketamine. Seven studies
      delivered a dose of 0.5 mg/kg intravenously over 40 min, while one study
      administered a 0.2 mg/kg intravenous bolus and another study administered a
      liquid suspension. The earliest significant results were seen after 40 min, and
      the longest results were observed up to 10 days postinfusion. CONCLUSION:
      Consistent with clinical research on ketamine as a rapid and effective treatment
      for depression, ketamine has shown early preliminary evidence of a reduction in
      depressive symptoms, as well as reducing SI, with minimal short-term side
      effects. Additional studies are needed to further investigate its mechanism of
      action, long-term outcomes, and long-term adverse effects (including abuse) and
      benefits. In addition, ketamine could potentially be used as a prototype for
      further development of rapid-acting antisuicidal medication with a practical
      route of administration and the most favorable risk/benefit ratio.

PMID- 25773963
TI  - Reactions of phenylacetylene with nickel POCOP-pincer hydride complexes resulting
      in different outcomes from their palladium analogues.
AB  - Nickel POCOP-pincer hydride complexes [2,6-(R2PO)2C6H3]NiH (R = (I)Pr, 4a; R =
      (c)Pe = cyclopentyl, 4b) react with phenylacetylene to generate [2,6
      (R2PO)2C6H3]NiC(Ph)=CH2 (5a-b) as the major product and (E)-[2,6
      (R2PO)2C6H3]NiCH=CHPh (6a-b) as the minor product. The 2,1-insertion is more
      favorable than the 1,2-insertion and both pathways involve cis addition of Ni-H
      across the C=C bond. Unlike the palladium case, alkynyl complexes [2,6
      (R2PO)2C6H3]NiC=CPh (7a-b) and H2 are not produced in the nickel system. The more
      bulky hydride complex [2,6-((t)Bu2PO)2C6H3]NiH (4c) shows no reactivity towards
      phenylacetylene. Catalytic hydrogenation of phenylacetylene with 4a-b takes place
      at an elevated temperature (70-100  degrees C) and proves to be heterogeneous.
      The structures of 5b, 6a, 7a and 7b have been studied by X-ray crystallography.

PMID- 25773964
TI  - A novel hNIS/tdTomato fusion reporter for visualizing the relationship between
      the cellular localization of sodium iodide symporter and its iodine uptake
      function under heat shock treatment.
AB  - The function of membrane-localized sodium iodide symporter (NIS) determines the
      efficacy of radioiodine therapy in thyroid cancer. Here, we describe a dual mode
      reporter fused with human NIS (hNIS) and a red fluorescent protein named tandem
      dimeric Tomato (tdTomato) for the in vitro and in vivo imaging of hNIS protein
      expression, localization, and iodide uptake function. Human cervical epithelial
      adenocarcinoma cell line (HeLa)-hNIS/tdTomato cells were established by
      transducing a fusion gene expressing hNIS/tdTomato under the control of a
      cytomegalovirus promoter. Fluorescence imaging, confocal microscopy, and an 125I
      uptake assay were performed to validate the integrity of the fusion protein.
      Actinomycin D and cycloheximide were used to block newly synthesized hNIS
      proteins. In vivo images were acquired using a gamma camera and a Maestro
      fluorescence imaging device. The fluorescence intensity of membrane-localized
      hNIS and 125I uptake both were increased after heat shock. Scintigraphy and
      fluorescence imaging indicated specific accumulation of the hNIS/tdTomato fusion
      protein in xenografted tumors, supporting the utility of this system for in vivo
      monitoring of hNIS expression and activity. We developed a novel hNIS/tdTomato
      dual mode reporter that enables visualization of the expression, localization,
      and iodine uptake function of hNIS in vitro and in vivo.

PMID- 25773965
TI  - Bridging a 30 mm defect in the canine ulnar nerve using vessel-containing
      conduits with implantation of bone marrow stromal cells.
AB  - Previously, we showed that undifferentiated bone marrow stromal cell (uBMSC)
      implantation and vessel insertion into a nerve conduit facilitated peripheral
      nerve regeneration in a rodent model. In this study, we investigated the efficacy
      of the uBMSC-laden vessel-containing conduit in repair of segmental nerve
      defects, using a canine model. Eight beagle dogs were used in this study. Thirty
      millimeter ulnar nerve defects were repaired with the conduits (right forelimbs,
      n = 8) or autografts (left forelimbs, n = 7). In the conduit group, the ulnar
      artery was inserted into the l-lactide/epsilon-caprolactone tube, which was
      filled with autologous uBMSCs obtained from the ilium. In the autograft group,
      the reversed nerve segments were sutured in situ. At 8 weeks, one dog with only
      nerve repair with the conduit was sacrificed and the regenerated nerve in the
      conduit underwent immunohistochemistry for investigation of the differentiation
      capability of the implanted uBMSCs. In the remaining seven dogs, the repaired
      nerves underwent electrophysiological examination at 12 and 24 weeks and
      morphometric measurements at 24 weeks. The wet weight of hypothenar muscles was
      measured at 24 weeks. At 8 weeks, almost 35% of the implanted uBMSCs expressed
      glial markers. At 12 weeks, amplitude (0.4 +/- 0.4mV) and conduction velocity
      (18.9 +/- 14.3m/s) were significantly lower in the conduit group than in the
      autograft group (3.2 +/- 2.5 mV, 34.9 +/- 12.1 m/s, P < 0.05). Although the nerve
      regeneration in the conduit group was inferior when compared with the autograft
      group at 24 weeks, there were no significant differences between both groups,
      regarding amplitude (10.9 +/- 7.3 vs. 25.3 +/- 20.1 mV; P = 0.11), conduction
      velocity (23.5 +/- 8.7 vs 31.6 +/- 20.0m/s; P = 0.35), myelinated axon number
      (7032 +/- 4188 vs 7165 +/- 1814; P = 0.94), diameter (1.73 +/- 0.31 vs 2.09 +/-
      0.39MUm; P = 0.09), or muscle weight (1.02 +/- 0.40 vs 1.19 +/- 0.26g; P = 0.36).
      In conclusion, this study showed that vessel-containing tubes with uBMSC
      implantation may be an option for treatment of peripheral nerve injuries.
      However, further investigations are needed. (c) 2015 Wiley Periodicals, Inc.
      Microsurgery 36:316-324, 2016. 

PMID- 25773966
TI  - Addition of a Decision Point in Evidence-Based Practice Process Steps to
      Distinguish EBP, Research and Quality Improvement Methodologies.
AB  - This column shares the best evidence-based strategies and innovative ideas on how
      to facilitate the learning of EBP principles and processes by clinicians as well
      as nursing and interprofessional students. Guidelines for submission are
      available at http://onlinelibrary.wiley.com/journal/10.1111/(ISSN)1741--6787. 

PMID- 25773967
TI  - Insufficient evidence for changing editorial policy.

PMID- 25773968
TI  - Optical theorem for two-dimensional (2D) scalar monochromatic acoustical beams in
      cylindrical coordinates.
AB  - The optical theorem for plane waves is recognized as one of the fundamental
      theorems in optical, acoustical and quantum wave scattering theory as it relates
      the extinction cross-section to the forward scattering complex amplitude
      function. Here, the optical theorem is extended and generalized in a cylindrical
      coordinates system for the case of 2D beams of arbitrary character as opposed to
      plane waves of infinite extent. The case of scalar monochromatic acoustical
      wavefronts is considered, and generalized analytical expressions for the
      extinction, absorption and scattering cross-sections are derived and extended in
      the framework of the scalar resonance scattering theory. The analysis reveals the
      presence of an interference scattering cross-section term describing the
      interaction between the diffracted Franz waves with the resonance elastic waves.
      The extended optical theorem in cylindrical coordinates is applicable to any
      object of arbitrary geometry in 2D located arbitrarily in the beam's path.
      Related investigations in optics, acoustics and quantum mechanics will benefit
      from this analysis in the context of wave scattering theory and other phenomena
      closely connected to it, such as the multiple scattering by a cloud of particles,
      as well as the resulting radiation force and torque. 

PMID- 25773969
TI  - Thermosonic Chladni figures for defect-selective imaging.
AB  - Thermosonic patterns produced by resonant vibrations of simulated and realistic
      defects are experimentally observed and compared with conventional vibration
      Chladni figures. The patterns are interpreted on the basis of hysteretic damping
      model that accounts for in-plane polarization component of vibrations. The
      analysis and simulation results show that thermosonic Chladni figures are the
      patterns of dissipation of vibration energy determined by a square of the in
      plane strain developed in the resonant vibrations. The difference in nodal
      patterns between the two types of Chladni figures is due to additional extension
      compression of the material mainly in near boundary area. The contribution of
      various order resonance modes in single-frequency imaging is illustrated and
      their superposition is shown to produce a full-scale thermosonic image of a
      resonant defect in a wideband excitation mode. 

PMID- 25773970
TI  - Albuminated PLGA nanoparticles containing bevacizumab intended for ocular
      neovascularization treatment.
AB  - Bevacizumab, an anti-VEGF antibody, has demonstrated trustworthy effects in
      treatment of retinal and choroidal neovascularization that both are crucial sight
      threatening conditions. However, the weak point is the short half-life of the
      drug in vitreous which necessitates frequent intravitreal injections. Accordingly
      employing controlled-release drug delivery systems such as polymeric
      nanoparticles (NPs) has been suggested. In this study albuminated-PLGA-NPs
      containing bevacizumab were prepared and studied intended for reducing the number
      of injections. NPs were formulated by double-emulsion method and a single dose of
      NPs was intravitreally injected to rabbits. The drug concentrations in vitreous
      and aqueous humor were assayed in different time intervals using ELISA and
      intraocular pharmacokinetic parameters were calculated. Moreover, coumarin-6
      loaded albuminated-PLGA-NPs were employed to evaluate the distribution and
      persistence of the NPs in the posterior segment. Results revealed that the
      bevacizumab vitreous concentration maintained above 500 ng mL(-1) for about 8
      weeks and 3.3 times elevation was observed in the drug vitreous MRT compared with
      the control. According to coumarin-6 NP tests, fluorescence emissions in
      posterior tissues were observed for 56 days which confirmed the nanoparticles
      persistence in ocular tissues during the test span. Therefore our prepared
      formulation may offer improvements in treatment of eye posterior segment
      neovascularization.

PMID- 25773971
TI  - DNA mismatch repair deficiency accelerates lung neoplasm development in K
      ras(LA1/+) mice: a brief report.
AB  - Inherited as well as acquired deficiencies in specific DNA mismatch repair (MMR)
      components are associated with the development of a wide range of benign and
      malignant neoplasms. Loss of key members such as MSH2 and MLH1 severely cripples
      the ability of the cell to recognize and correct such lesions as base:base
      mismatches and replicative DNA polymerase errors such as slippages at repetitive
      sequences. Genomic instability resulting from MMR deficiency not only predisposes
      cells to malignant transformation but may also promote tumor progression. To test
      the latter, we interbred Msh2(-/-) mice with the K-ras(LA1/+) transgenic line
      that spontaneously develops a range of premalignant and malignant lung lesions.
      Compared to K-ras(LA1/+) mice, K-ras(LA1/+); Msh2(-/-) mice developed lung
      adenomas and adenocarcinomas at an increased frequency and also demonstrated
      evidence of accelerated adenocarcinoma growth. Since MMR defects have been
      identified in some human lung cancers, the mutant mice may not only be of
      preclinical utility but they will also be useful in identifying gene alterations
      able to act in concert with Kras mutants to promote tumor progression.

PMID- 25773972
TI  - Recent approaches for on-line analysis of residues and contaminants in food
      matrices: A review.
AB  - This review highlights recent developments for on-line determination of residues
      and contaminants in complex matrices such as food samples. This involves the on
      line coupling of a sample preparation technique (as the first "dimension") with a
      chromatographic system (second "dimension"), usually followed by mass
      spectrometry. Although frequently treated as quite distinct techniques, the role
      of all devices utilized as the first dimension in this approach aims to decrease
      the sample complexity while eliminating as much as possible the matrix
      contaminants to facilitate the qualitative and quantitative determination of the
      compounds of interest. This review will focus on the following techniques as the
      first dimension: (i) on-line solid-phase extraction; (ii) in-tube solid-phase
      microextraction; (iii) matrix solid-phase dispersion; and (iv) turbulent flow
      chromatography. The second dimension is usually performed using a chromatographic
      column to isolate the analyte(s) of interest for further mass spectrometry
      determination. A description of the basis of this on-line approach and its
      distinct set up possibilities is presented, which is followed by a critical
      review of the literature covering this subject in the last ten years (focusing on
      the last five years) with emphasis on the analysis of residue and contaminants in
      food samples. 

PMID- 25773973
TI  - Improving survival and storage stability of bacteria recalcitrant to freeze
      drying: a coordinated study by European culture collections.
AB  - The objective of this study is to improve the viability after freeze-drying and
      during storage of delicate or recalcitrant strains safeguarded at biological
      resource centers. To achieve this objective, a joint experimental strategy was
      established among the different involved partner collections of the EMbaRC
      project ( www.embarc.eu ). Five bacterial strains considered as recalcitrant to
      freeze-drying were subjected to a standardized freeze-drying protocol and to
      seven agreed protocol variants. Viability of these strains was determined before
      and after freeze-drying (within 1 week, after 6 and 12 months, and after
      accelerated storage) for each of the protocols. Furthermore, strains were
      exchanged between partners to perform experiments with different freeze-dryer
      dependent parameters. Of all tested variables, choice of the lyoprotectant had
      the biggest impact on viability after freeze-drying and during storage. For
      nearly all tested strains, skim milk as lyoprotectant resulted in lowest
      viability after freeze-drying and storage. On the other hand, best freeze-drying
      and storage conditions were strain and device dependent. For Aeromonas
      salmonicida CECT 894(T), best survival was obtained when horse serum supplemented
      with trehalose was used as lyoprotectant, while Aliivibrio fischeri LMG 4414(T)
      should be freeze-dried in skim milk supplemented with marine broth in a 1:1
      ratio. Freeze-drying Campylobacter fetus CIP 53.96(T) using skim milk
      supplemented with trehalose as lyoprotectant resulted in best recovery.
      Xanthomonas fragariae DSM 3587(T) expressed high viability after freeze-drying
      and storage for all tested lyoprotectants and could not be considered as
      recalcitrant. In contrary, Flavobacterium columnare LMG 10406(T) did not survive
      the freeze-drying process under all tested conditions.

PMID- 25773974
TI  - Improved productivity of poly (3-hydroxybutyrate) (PHB) in thermophilic
      Chelatococcus daeguensis TAD1 using glycerol as the growth substrate in a fed
      batch culture.
AB  - A particularly successful polyhydroxyalkanoate (PHA) in industrial applications
      is poly (3-hydroxybutyrate) (PHB). However, one of the major obstacles for wider
      application of PHB is the cost of its production and purification. Therefore, it
      is desirable to discover a method for producing PHB in large quantities at a
      competitive price. Glycerol is a cheap and widely used carbon source that can be
      applied in PHB production process. There are numerous advantages to operating
      fermentation at elevated temperatures; only several thermophilic bacteria are
      able to accumulate PHB when glycerol is the growth substrate. Here, we report on
      the possibility of increasing PHB production at low cost using thermophilic
      Chelatococcus daeguensis TAD1 when glycerol is the growth substrate in a fed
      batch culture. We found that (1) excess glycerol inhibited PHB accumulation and
      (2) organic nitrogen sources, such as tryptone and yeast extract, promoted the
      growth of C. daeguensis TAD1. In the batch fermentation experiments, we found
      that using glycerol at low concentrations as the sole carbon source, along with
      the addition of mixed nitrate (NH4Cl, tryptone, and yeast extract), stimulated
      PHB accumulation in C. daeguensis TAD1. The results showed that the PHB
      productivity decreased in the following order: two-stage fed-batch fermentation >
      fed-batch fermentation > batch fermentation. In optimized culture conditions, a
      PHB amount of 17.4 g l(-1) was obtained using a two-stage feeding regimen,
      leading to a productivity rate of 0.434 g l(-1) h(-1), which is the highest
      productivity rate reported for PHB to date. This high PHB biosynthetic
      productivity could decrease the total production cost, allowing for further
      development of industrial applications of PHB.

PMID- 25773975
TI  - Fungal volatile organic compounds and their role in ecosystems.
AB  - All odorants are volatile organic compounds (VOCs), i.e., low molecular weight
      compounds that easily evaporate at normal temperatures and pressure. Fungal VOCs
      are relatively understudied compared to VOCs of bacterial, plant, or synthetic
      origin. Much of the research to date on fungal VOCs has focused on their food and
      flavor properties, their use as indirect indicators of fungal growth in
      agriculture, or their role as semiochemicals for insects. In addition, research
      into fungal volatiles has also taken place to monitor spoilage, for purposes of
      chemotaxonomy, for use in biofilters and for biodiesel, to detect plant and
      animal disease, for "mycofumigation," and with respect to plant health. As
      methods for the analysis of gas phase molecules have improved, it has become
      apparent that fungal VOC are more chemically varied and more biologically active
      than has generally been realized. In particular, there is increasing data that
      show that fungal VOCs frequently mediate interactions between organisms within
      and across different ecological niches. The goal of this mini review is to
      orchestrate data on fungal VOCs obtained from disparate disciplines as well as to
      draw attention to the ecological importance of fungal VOCs in signaling between
      different species. Technologies and approaches that are common in one area of
      research are often unknown in others, and the study of fungal VOCs would benefit
      from more cross talk between subdisciplines.

PMID- 25773976
TI  - Identification and regulation of the catalytic promiscuity of (-)-gamma-lactamase
      from Microbacterium hydrocarbonoxydans.
AB  - Mhg, a previously reported (-)-gamma-lactamase from Microbacterium
      hydrocarbonoxydans, was identified to have perhydrolase activity by combining
      structure similarity search with activity assays. Kinetic studies illustrated
      that perhydrolysis was the native activity owing to lower K m and higher k cat/K
      m values. Experimental evidence showed that both hydrolysis and perhydrolysis
      reactions took place at the same active center. Engineering of the putative
      substrate-binding pocket revealed that Leu233 site played a vital role in the
      aspects of selective catalysis, soluble protein expression level and optimum
      temperature shift, etc. The mutants L233A, L233P, and L233T retained (-)-gamma
      lactamase activity but lost perhydrolase activity, while L233M only kept
      perhydrolase activity. Substitutions of Leu233 could dramatically influence the
      state of expressed protein. Computational analysis explicitly explained the
      relationships between mutations and gamma-lactamase activity changes. Our
      investigations demonstrated that it was an efficient method to identify the
      enzyme catalytic promiscuity by combining 3D structure alignment with activity
      validations, and engineering of substrate-binding pocket could serve as a
      promising way to regulate activities of promiscuous enzymes. 

PMID- 25773977
TI  - Denitrifying sulfide removal process on high-salinity wastewaters.
AB  - Denitrifying sulfide removal (DSR) process comprising both heterotrophic and
      autotrophic denitrifiers can simultaneously convert nitrate, sulfide, and acetate
      into nitrogen gas, elemental sulfur (S(0)), and carbon dioxide, respectively.
      Sulfide- and nitrate-laden wastewaters at 2-35 g/L NaCl were treated by DSR
      process. A C/N ratio of 3:1 was proposed to maintain high S(0) conversion rate.
      The granular sludge with a compact structure and smooth outer surface was formed.
      The microbial communities of DSR consortium via high-throughput sequencing method
      suggested that salinity shifts the predominating heterotrophic denitrifiers at
      <10 g/L NaCl to autotrophic denitrifiers at >10 g/L NaCl. 

PMID- 25773978
TI  - Dry anaerobic digestion of high solids content dairy manure at high organic
      loading rates in psychrophilic sequence batch reactor.
AB  - Cow manure with bedding is renewable organic biomass available around the year on
      dairy farms. Developing efficient and cost-effective psychrophilic dry anaerobic
      digestion (PDAD) processes could contribute to solving farm-related
      environmental, energy, and manure management problems in cold-climate regions.
      This study was to increase the organic loading rate (OLR), fed to a novel
      psychrophilic (20  degrees C) dry anaerobic digestion of 27% total solid dairy
      manure (cow feces and wheat straw) in sequence batch reactor (PDAD-SBR), by 133
      to 160%. The PDAD-SBR process operated at treatment cycle length of 21 days and
      OLR of 7.0 and 8.0 g total chemical oxygen demand (TCOD) kg(-1) inoculum day(-1)
      (5.2 +/- 0.1 and 5.8 +/- 0.0 g volatile solids (VS) kg(-1) inoculum day(-1)) for
      four successive cycles (84 days) produced average specific methane yields (SMYs)
      of 147.1 +/- 17.2 and 143.2 +/- 11.7 normalized liters (NL) CH4 kg(-1) VS fed,
      respectively. PDAD of cow feces and wheat straw is possible with VS-based
      inoculum-to-substrate ratio of 1.45 at OLR of 8.0 g TCOD kg(-1) inoculum day(-1).
      Hydrolysis was the limiting step reaction. The VS removal averaged around 57.4 +/
      0.5 and 60.5 +/- 5.7% at OLR 7.0 and 8.0 g TCOD kg(-1) inoculum day(-1),
      respectively.

PMID- 25773979
TI  - Cell surface display of Yarrowia lipolytica lipase Lip2p using the cell wall
      protein YlPir1p, its characterization, and application as a whole-cell
      biocatalyst.
AB  - The Yarrowia lipolytica lipase Lip2p was displayed on the yeast cell surface via
      N-terminal fusion variant using cell wall protein YlPir1p. The hydrolytic
      activity of the lipase displayed on Y. lipolytica cells reached 11,900 U/g of dry
      weight. However, leakage of enzyme from the cell wall was observed. The
      calculated number of recombinant enzyme displayed on the cell surface corresponds
      to approximately 6 * 10(5) molecules per cell, which is close to the theoretical
      maximum (2 * 10(6) molecules/cell). Furthermore, the leaking enzyme was presented
      as three N-glycosylated proteins, one of which corresponds to the whole hybrid
      protein. Thus, we attribute the enzyme leakage to the limited space available on
      the cell surface. Nevertheless, the surface-displayed lipase exhibited greater
      stability to short-term and long-term temperature treatment than the native
      enzyme. Cell-bound lipase retained 74 % of its original activity at 60  degrees C
      for 5 min of incubation, and 83 % of original activity after incubation at 50 
      degrees C during 5 h. Cell-bound lipase had also higher stability in organic
      solvents and detergents. The developed whole-cell biocatalyst was used for
      recycling biodiesel synthesis. Two repeated cycles of methanolysis yielded 84.1
      and 71.0 % methyl esters after 33- and 45-h reactions, respectively.

PMID- 25773980
TI  - Biogas by semi-continuous anaerobic digestion of food waste.
AB  - The semi-continuous anaerobic digestion of food waste was investigated in 1-L and
      20-L continuously stirred tank reactors (CSTRs), to identify the optimum
      operation condition and the methane production of the semi-continuous anaerobic
      process. Results from a 1-L digester indicated that the optimum organic loading
      rate (OLR) for semi-continuous digestion is 8 g VS/L/day. The corresponding
      methane yield and chemical oxygen demand (COD) reduction were 385 mL/g VS and
      80.2 %, respectively. Anaerobic digestion was inhibited at high OLRs (12 and 16 g
      VS/L/day), due to volatile fatty acid (VFA) accumulation. Results from a 20-L
      digester indicated that a higher methane yield of 423 mL/g VS was obtained at
      this larger scale. The analysis showed that the methane production at the optimum
      OLR fitted well with the determined kinetics equation. An obvious decrease on the
      methane content was observed at the initial of digestion. The increased
      metabolization of microbes and the activity decrease of methanogen caused by VFA
      accumulation explained the lower methane content at the initial of digestion.

PMID- 25773981
TI  - The exploratory power of sleep effort, dysfunctional beliefs and arousal for
      insomnia severity and polysomnography-determined sleep.
AB  - Differences between subjective sleep perception and sleep determined by
      polysomnography (PSG) are prevalent, particularly in patients with primary
      insomnia, indicating that the two measures are partially independent. To identify
      individualized treatment strategies, it is important to understand the
      potentially different mechanisms influencing subjective and PSG-determined sleep.
      The aim of this study was to investigate to what extent three major components of
      insomnia models, i.e., sleep effort, dysfunctional beliefs and attitudes about
      sleep, and presleep arousal, are associated with subjective insomnia severity and
      PSG-determined sleep. A sample of 47 patients with primary insomnia according to
      DSM-IV criteria and 52 good sleeper controls underwent 2 nights of PSG and
      completed the Glasgow Sleep Effort Scale, the Dysfunctional Beliefs and Attitudes
      about Sleep Scale, the Pre-Sleep Arousal Scale and the Insomnia Severity Index.
      Regression analyses were conducted to investigate the impact of the three
      predictors on subjective insomnia severity and PSG- determined total sleep time.
      All analyses were adjusted for age, gender, depressive symptoms and group status.
      The results showed that subjective insomnia severity was associated positively
      with sleep effort. PSG-determined total sleep time was associated negatively with
      somatic presleep arousal and dysfunctional beliefs and attitudes about sleep.
      This pattern of results provides testable hypotheses for prospective studies on
      the impact of distinct cognitive and somatic variables on subjective insomnia
      severity and PSG-determined total sleep time.

PMID- 25773982
TI  - Characterisation of Elastic and Acoustic Properties of an Agar-Based Tissue
      Mimicking Material.
AB  - As a first step towards an acoustic localisation device for coronary stenosis to
      provide a non-invasive means of diagnosing arterial disease, measurements are
      reported for an agar-based tissue mimicking material (TMM) of the shear wave
      propagation velocity, attenuation and viscoelastic constants, together with one
      dimensional quasi-static elastic moduli and Poisson's ratio. Phase velocity and
      attenuation coefficients, determined by generating and detecting shear waves
      piezo-electrically in the range 300 Hz-2 kHz, were 3.2-7.5 ms(-1) and 320 dBm(
      1). Quasi-static Young's modulus, shear modulus and Poisson's ratio, obtained by
      compressive or shear loading of cylindrical specimens were 150-160 kPa; 54-56 kPa
      and 0.37-0.44. The dynamic Young's and shear moduli, derived from fitting
      viscoelastic internal variables by an iterative statistical inverse solver to
      freely oscillating specimens were 230 and 33 kPa and the corresponding relaxation
      times, 0.046 and 0.036 s. The results were self-consistent, repeatable and
      provide baseline data required for the computational modelling of wave
      propagation in a phantom. 

PMID- 25773983
TI  - Editorial: Scaffolds for regenerative medicine: a special issue of the Annals of
      Biomedical Engineering.

PMID- 25773984
TI  - A cascaded QSAR model for efficient prediction of overall power conversion
      efficiency of all-organic dye-sensitized solar cells.
AB  - A cascaded model is proposed to establish the quantitative structure-activity
      relationship (QSAR) between the overall power conversion efficiency (PCE) and
      quantum chemical molecular descriptors of all-organic dye sensitizers. The
      cascaded model is a two-level network in which the outputs of the first level
      (JSC, VOC, and FF) are the inputs of the second level, and the ultimate end-point
      is the overall PCE of dye-sensitized solar cells (DSSCs). The model combines
      quantum chemical methods and machine learning methods, further including quantum
      chemical calculations, data division, feature selection, regression, and
      validation steps. To improve the efficiency of the model and reduce the
      redundancy and noise of the molecular descriptors, six feature selection methods
      (multiple linear regression, genetic algorithms, mean impact value, forward
      selection, backward elimination, and +n-m algorithm) are used with the support
      vector machine. The best established cascaded model predicts the PCE values of
      DSSCs with a MAE of 0.57 (%), which is about 10% of the mean value PCE (5.62%).
      The validation parameters according to the OECD principles are R(2) (0.75), Q(2)
      (0.77), and Qcv2 (0.76), which demonstrate the great goodness-of-fit,
      predictivity, and robustness of the model. Additionally, the applicability domain
      of the cascaded QSAR model is defined for further application. This study
      demonstrates that the established cascaded model is able to effectively predict
      the PCE for organic dye sensitizers with very low cost and relatively high
      accuracy, providing a useful tool for the design of dye sensitizers with high
      PCE.

PMID- 25773985
TI  - Molecular mechanisms of subretinal fibrosis in age-related macular degeneration.
AB  - Subretinal fibrosis is a result of a wound healing response that follows
      choroidal neovascularization in neovascular age-related macular degeneration
      (nAMD). Although anti-vascular endothelial growth factor therapy has become a
      standard treatment that improves visual acuity in many nAMD patients,
      unsuccessful treatment outcomes have often been attributed to the progression of
      subretinal fibrosis. In this review, we summarize the cellular and extracellular
      components of subretinal fibrous membranes and also discuss the possible
      molecular mechanisms including the functional involvement of growth factors and
      the inflammatory response in the process. Moreover, we present an murine animal
      model of subretinal fibrosis that might facilitate greater understanding of the
      pathophysiology and the development of novel therapeutic strategies for the
      inhibition of subretinal fibrosis in nAMD. 

PMID- 25773987
TI  - Metabolomic composition of normal aged and cataractous human lenses.
AB  - Quantitative metabolomic profiles of normal and cataractous human lenses were
      obtained with the combined use of high-frequency nuclear magnetic resonance (NMR)
      and high-performance liquid chromatography with high-resolution mass
      spectrometric detection (LC-MS) methods. The concentration of more than fifty
      metabolites in the lens cortex and nucleus has been determined. For the majority
      of metabolites, their concentrations in the lens cortex and nucleus are similar,
      which confirms low metabolic activity in the lens core. The difference between
      the metabolite levels in the cortex and nucleus of the normal lens is observed
      for antioxidants and UV filters, which demonstrates the activity of redox
      processes in the lens. A huge difference is found between the metabolomic
      compositions of normal and age-matched cataractous lenses: the concentrations of
      almost all metabolites in the normal lens are higher than in the cataractous one.
      The most pronounced difference is observed for compounds playing a key role in
      the lens cell protection and metabolic activity, including antioxidants, UV
      filters, and osmolytes. The results obtained imply that the development of the
      age-related cataracts might originate from the metabolic dysfunction of the lens
      epithelial cells. 

PMID- 25773986
TI  - A test of lens opacity as an indicator of preclinical Alzheimer Disease.
AB  - Previous studies reported that characteristic lens opacities were present in
      Alzheimer Disease (AD) patients postmortem. We therefore determined whether
      cataract grade or lens opacity is related to the risk of Alzheimer dementia in
      participants who have biomarkers that predict a high risk of developing the
      disease. AD biomarker status was determined by positron emission tomography
      Pittsburgh compound B (PET-PiB) imaging and cerebrospinal fluid (CSF) levels of
      Abeta42. Cognitively normal participants with a clinical dementia rating of zero
      (CDR = 0; N = 40) or with slight evidence of dementia (CDR = 0.5; N = 2) were
      recruited from longitudinal studies of memory and aging at the Washington
      University Knight Alzheimer's Disease Research Center. The age, sex, race,
      cataract type and cataract grade of all participants were recorded and an
      objective measure of lens light scattering was obtained for each eye using a
      Scheimpflug camera. Twenty-seven participants had no biomarkers of Alzheimer
      dementia and were CDR = 0. Fifteen participants had biomarkers indicating
      increased risk of AD, two of which were CDR = 0.5. Participants who were
      biomarker positive were older than those who were biomarker negative. Biomarker
      positive participants had more advanced cataracts and increased cortical light
      scattering, none of which reached statistical significance after adjustment for
      age. We conclude that cataract grade or lens opacity is unlikely to provide a non
      invasive measure of the risk of developing Alzheimer dementia. 

PMID- 25773988
TI  - RE: The value of TRUS in the staging of rectal carcinoma before and after
      radiotherapy and comparison with the staging postoperative pathology.

PMID- 25773989
TI  - In vivo neurometabolic profiling in patients with spinocerebellar ataxia types 1,
      2, 3, and 7.
AB  - Spinocerebellar ataxias (SCAs) belong to polyglutamine repeat disorders and are
      characterized by a predominant atrophy of the cerebellum and the pons. Proton
      magnetic resonance spectroscopy ((1) H MRS) using an optimized semiadiabatic
      localization by adiabatic selective refocusing (semi-LASER) protocol was
      performed at 3 T to determine metabolite concentrations in the cerebellar vermis
      and pons of a cohort of patients with SCA1 (n=16), SCA2 (n=12), SCA3 (n=21), and
      SCA7 (n=12) and healthy controls (n=33). Compared with controls, patients
      displayed lower total N-acetylaspartate and, to a lesser extent, lower glutamate,
      reflecting neuronal loss/dysfunction, whereas the glial marker, myoinositol (myo
      Ins), was elevated. Patients also showed higher total creatine as reported in
      Huntington's disease, another polyglutamine repeat disorder. A strong correlation
      was found between the Scale for the Assessment and Rating of Ataxia and the
      neurometabolites in both affected regions of patients. Principal component
      analyses confirmed that neuronal metabolites (total N-acetylaspartate and
      glutamate) were inversely correlated in the vermis and the pons to glial (myo
      Ins) and energetic (total creatine) metabolites, as well as to disease severity
      (motor scales). Neurochemical plots with selected metabolites also allowed the
      separation of SCA2 and SCA3 from controls. The neurometabolic profiles detected
      in patients underlie cell-specific changes in neuronal and astrocytic
      compartments that cannot be assessed by other neuroimaging modalities. The
      inverse correlation between metabolites from these two compartments suggests a
      metabolic attempt to compensate for neuronal damage in SCAs. Because these
      biomarkers reflect dynamic aspects of cellular metabolism, they are good
      candidates for proof-of-concept therapeutic trials. (c) 2015 International
      Parkinson and Movement Disorder Society.

PMID- 25773990
TI  - Effect of grass pollen immunotherapy on clinical and local immune response to
      nasal allergen challenge.
AB  - RATIONALE: Nasal allergen provocations may be useful in investigating the
      pathophysiology of allergic rhinitis and effects of treatments. OBJECTIVE: To use
      grass pollen nasal allergen challenge (NAC) to investigate the effects of
      allergen immunotherapy in a cross-sectional study. METHODS: We studied nasal and
      cutaneous responses in untreated subjects with seasonal grass-pollen allergic
      rhinitis (n = 14) compared with immunotherapy-treated allergics (n = 14), plus a
      nonatopic control group (n = 14). Volunteers underwent a standardized NAC with
      2000 biological units of timothy grass allergen (equivalent to 1.3 MUg major
      allergen, Phl p5). Nasal fluid was collected and analysed by ImmunoCAP and
      multiplex assays. Clinical response was assessed by symptom scores and peak nasal
      inspiratory flow (PNIF). Cutaneous response was measured by intradermal allergen
      injection. Retrospective seasonal symptom questionnaires were also completed.
      RESULTS: Immunotherapy-treated patients had lower symptom scores (P = 0.04) and
      higher PNIF (P = 0.02) after challenge than untreated allergics. They had reduced
      early (P = 0.0007) and late (P < 0.0001) skin responses, and lower retrospective
      seasonal symptom scores (P < 0.0001). Compared to untreated allergics,
      immunotherapy-treated patients had reduced nasal fluid concentrations of IL-4, IL
      9 and eotaxin (all P < 0.05, 8 h level and/or area under the curve comparison),
      and trends for reduced IL-13 (P = 0.07, area under the curve) and early-phase
      tryptase levels (P = 0.06). CONCLUSIONS: Nasal allergen challenge is sensitive in
      the detection of clinical and biological effects of allergen immunotherapy and
      may be a useful surrogate marker of treatment efficacy in future studies.

PMID- 25773991
TI  - Diabetes Connect: African American Women's Perceptions of the Community Health
      Worker Model for Diabetes Care.
AB  - Community health worker (CHW) interventions have potential to improve diabetes
      outcomes and reduce health disparities. However, few studies have explored
      patient perspectives of peer-delivered diabetes programs. The purpose of this
      qualitative study is to investigate possible benefits as well as risks of CHW
      delivered peer support for diabetes from the perspectives of African American
      women living with type 2 diabetes in Jefferson County, Alabama. Four ninety
      minute focus groups were conducted by a trained moderator with a written guide to
      facilitate discussion on the topic of CHWs and diabetes management. Participants
      were recruited from the diabetes education database at a safety-net hospital. Two
      independent reviewers performed content analysis to identify major themes using a
      combined deductive-inductive approach. There were 25 participants. Mean years
      with diabetes was 11.2 (range 6 months to 42 years). Participants were
      knowledgeable about methods for self-management but reported limited resources
      and stress as major barriers. Preferred CHW roles included liaison to the
      healthcare system and easily accessible information source. Participants
      preferred that the CHW be knowledgeable and have personal experience managing
      their own diabetes or assisting a family member with diabetes. Concerns regarding
      the CHW-model were possible breaches of confidentiality and privacy. The self
      management strategies and barriers to management identified by participants were
      reflected in their preferred CHW roles and traits. These results suggest that
      African American women with diabetes in Alabama would support peer-led diabetes
      education that is community-based and socially and emotionally supportive. 

PMID- 25773992
TI  - Oncogenic and Therapeutic Targeting of PTEN Loss in Bone Malignancies.
AB  - Being a tumor suppressor, PTEN functions as a dual-specificity protein and
      phospholipid phosphatase and regulates a variety of cellular processes and signal
      transduction pathways. Loss of PTEN function has been detected frequently in
      different forms of cancers, such as breast, prostate and lung cancer, gastric and
      colon cancer, skin cancer, as well as endometrial carcinoma. In this review, we
      provide a summary of PTEN and its role in bone malignancies including bone
      metastases, multiple myeloma, and osteosarcoma, etc. We highlight the importance
      of PTEN loss leading to activation of the oncogenic PI3K/Akt/mTOR pathway in
      tumorigenesis and progression, which can be attributed to both genetic and non
      genetic alterations involving gene mutation, loss of heterozygosity, promoter
      hypermethylation, and microRNA mediated negative regulation. We also discuss the
      emerging therapeutic applications targeting PTEN loss for the treatment of these
      bone malignant diseases.

PMID- 25773993
TI  - Optimization of alkaline sulfite pretreatment and comparative study with sodium
      hydroxide pretreatment for improving enzymatic digestibility of corn stover.
AB  - In this study, alkaline sulfite pretreatment of corn stover was optimized. The
      influences of pretreatments on solid yield, delignification, and carbohydrate
      recovery under different pretreatment conditions and subsequent enzymatic
      hydrolysis were investigated. The effect of pretreatment was evaluated by
      enzymatic hydrolysis efficiency and the total sugar yield. The optimum
      pretreatment conditions were obtained, as follows: the total titratable alkali
      (TTA) of 12%, liquid/solid ratio of 6:1, temperature of 140  degrees C, and
      holding time of 20 min. Under those conditions, the solid yield was 55.24%, and
      the removal of lignin was 82.68%. Enzymatic hydrolysis rates of glucan and xylan
      for pretreated corn stover were 85.38% and 70.36%, and the total sugar yield was
      74.73% at cellulase loading of 20 FPU/g and beta-glucosidase loading of 10 IU/g
      for 48 h. Compared with sodium hydroxide pretreatment with the same amount of
      total titratable alkali, the total sugar yield was raised by about 10.43%.
      Additionally, the corn stover pretreated under the optimum pretreatment
      conditions was beaten by PFI at 1500 revolutions. After beating, enzymatic
      hydrolysis rates of glucan and xylan were 89.74% and 74.06%, and the total sugar
      yield was 78.58% at the same enzymatic hydrolysis conditions. Compared with 1500
      rpm of PFI beating after sodium pretreatment with the same amount of total
      titratable alkali, the total sugar yield was raised by about 14.05%.

PMID- 25773994
TI  - A statistical approach for detecting common features.
AB  - BACKGROUND: With increasing numbers of datasets in neuroimaging studies, it has
      become an important task to pool information, in order to increase the
      statistical power of tests and for cross validation. However, no robust global
      approach unambiguously identifies the common biological abnormalities in, for
      example, resting-state functional magnetic resonance imaging in a number of
      mental disorders, where there are multiple datasets/attributes. Here we propose a
      novel and efficient statistical approach to this problem that finds common
      features in multiple datasets. NEW METHOD: By collecting the statistics of each
      dataset into a vector, our method uses a 'multi-dimensional local false
      discovery' rate to pool information and make full use of the joint distribution
      of datasets. RESULTS: We have tested our approach extensively on both simulated
      and clinical datasets. By conducting simulation studies, we find that our
      approach has a higher statistical power than existing approaches, especially on
      correlated datasets. Employing our approach on clinical data yields findings that
      are consistent with the existing literature. COMPARISON WITH EXISTING METHODS:
      Conventional methods cannot determine the false discovery rate underlying
      multiple datasets/attributes. Our approach can effectively handle these datasets.
      It has a solid Bayesian interpretation, and a higher power than other approaches
      in numerical simulations. This can be explained by the incorporation of
      correlations, between different attributes, into the new method. CONCLUSIONS: In
      this work, we present a natural, novel and powerful statistical approach to
      tackle situations involving multiple datasets or attributes. This new method has
      significant advantages over existing approaches and wide applications.

PMID- 25773995
TI  - The crisis in the emergency medicine physician scientist workforce.

PMID- 25773996
TI  - Bone marrow-derived mesenchymal stem cells differentiate into nerve-like cells in
      vitro after transfection with brain-derived neurotrophic factor gene.
AB  - Bone marrow-derived mesenchymal stem cells can differentiate into a variety of
      adult cells. Brain-derived neurotrophic factor (BDNF) is briefly active during
      differentiation and induces mesenchymal stem cells to differentiate into nerve
      cells. In this study, we cloned human BDNF to generate a recombinant pcDNA3.1(-)
      BDNF vector and transfected the vector into bone marrow-derived mesenchymal stem
      cells. We selected these cells with Geneticin-418 to obtain BDNF-BMSCs, which
      were induced with retinoic acid to obtain induced BDNF-BMSCs. The transfected
      cells displayed the typical morphology and surface antigen profile of fibroblasts
      and were observed to express clusters of differentiation 29, 44, and 90 (observed
      in matrix and stromal cells), but not clusters of differentiation 31, 34, and 45
      (observed in red blood cells and endothelial cells), via flow cytometry. Enzyme
      linked immunosorbent assays showed that transfected bone marrow-derived
      mesenchymal stem cells secreted more BDNF than non-transfected bone marrow
      derived mesenchymal stem cells. Immunocytochemistry and real-time reverse
      transcription polymerase chain reaction analysis showed that non-induced BDNF
      BMSCs maintained a higher proliferative capacity and expressed higher amounts of
      brain-derived neurotrophic factor, nestin, neuron-specific enolase, and glial
      fibrillary acid protein than non-transfected bone marrow-derived mesenchymal stem
      cells. An additional increase was observed in the induced BDNF-BMSCs compared to
      the non-induced BDNF-BMSCs. This expression profile is characteristic of
      neurocytes. Our data demonstrate that bone marrow-derived mesenchymal stem cells
      transfected with the BDNF gene can differentiate into nerve-like cells in vitro,
      which may enable the generation of sufficient quantities of nerve-like cells for
      treatment of neuronal diseases.

PMID- 25773997
TI  - Cerium: an unlikely replacement of dysprosium in high performance Nd-Fe-B
      permanent magnets.
AB  - Replacement of Dy and substitution of Nd in NdFeB-based permanent magnets by Ce,
      the most abundant and lowest cost rare earth element, is important because Dy and
      Nd are costly and critical rare earth elements. The Ce, Co co-doped alloys have
      excellent high-temperature magnetic properties with an intrinsic coercivity being
      the highest known for T >= 453 K. 

PMID- 25773998
TI  - Multifocal VEP provide electrophysiological evidence of predominant dysfunction
      of the optic nerve fibers derived from the central retina in Leber's hereditary
      optic neuropathy.
AB  - PURPOSE: To differentiate the bioelectrical cortical responses driven by axons
      from central and mid-peripheral retina in Leber's hereditary optic neuropathy
      (LHON) by using multifocal visual evoked potentials (mfVEP). METHODS: Seventeen
      genetically confirmed LHON patients (33.35 +/- 8.4 years, 17 eyes) and 22 age
      matched controls (C) (38.2 +/- 6.0 years, 22 eyes) were studied by mfVEP and
      optical coherence tomography. MfVEP P1 implicit time (P1 IT, ms) and response
      amplitude density of the N1-P1 components (N1-P1 RAD, nV/deg(2)) of the second
      order binary kernel were measured for five concentric retinal areas between the
      fovea and mid-periphery: 0-20 degrees (R1 to R5). RESULTS: Mean mfVEP P1 ITs and
      N1-P1 RADs at all five foveal eccentricities were significantly different (p <
      0.01) in LHON when compared to controls. In both groups, mean mfVEP responses
      obtained from R1 to R5 showed a progressive shortening of P1 ITs (linear fitting,
      LHON: r  = -0.95; C: r = -0.98) and decrease of N1-P1 RADs (exponential fitting,
      LHON: r (2) = 0.94; C: r (2) = 0.93). The slope of the linear fitting between
      mean mfVEP P1 ITs in the two groups was about three times greater in LHON than in
      controls (LHON: y = -13.33x +182.03; C: y = -4.528x +108.1). MfVEP P1 ITs
      detected in R1 and R2 (0-5 degrees) were significantly correlated (p < 0.01) with
      the reduction of retinal nerve fiber layer thickness of the temporal quadrant.
      CONCLUSIONS: MfVEP identifies abnormal neural conduction along the visual
      pathways in LHON, discriminating a predominant involvement of axons driving
      responses from the central retina when compared to those serving the mid
      peripheral retina.

PMID- 25774000
TI  - Nanodiamonds from coal under ambient conditions.
AB  - Coal is the most abundant energy resource, but it is only useful for producing
      energy via combustion due to its structural characteristics. However, coal is
      also inexpensive and is the most plentiful and readily available carbon source
      material for the production of nanodiamonds compared with the most widely used
      solid carbon source, high-purity graphite, and the high-purity hydrocarbon gas
      precursor, methane. Here, we report a simple and green top-down strategy for
      synthesizing nanodiamonds with a cubic phase and a mean size of 3 nm from various
      types of coal at atmospheric pressure and room temperature using a novel process
      involving laser ablation in liquid. Furthermore, we have systematically studied
      the process of phase transformation from coal to nanodiamonds using nucleation
      thermodynamics, growth kinetics and structural stability. The synthesized
      nanodiamonds have turned out to be soluble monodisperse colloids that exhibit
      strong and stable fluorescence both in alcohol and in water. These results
      provide a route for producing nanodiamonds from inexpensive and abundant coal. 

PMID- 25773999
TI  - Survey on skin-lightening practices and cosmetics in Kigali, Rwanda.
AB  - BACKGROUND: The use of skin-lightening (SL) cosmetics appears to be common
      throughout the world, especially among dark-skinned women from sub-Saharan
      Africa. OBJECTIVES: The aims of this study were to evaluate the extent of the
      practice of SL in Kigali, the capital city of Rwanda, the motivations behind this
      practice and the complexity of the adverse effects observed. METHODS: An
      inventory of products sold on the Kigali market and their contents were compared
      with the results of a survey investigating the products used by the local
      population in order to deduce the proportions of people who depigment. The
      prevalence and severity of SL side effects (dermatitis, skin cancers, etc.) were
      evaluated in collaboration with dermatologists and general practitioners through
      a specific questionnaire and interviews. The sociological profiles of adolescents
      and their motivations for practicing SL were studied using qualitative and
      descriptive approaches through semi-direct individual and collective interviews.
      RESULTS: A total of 27 creams were identified and classified according to labeled
      ingredients known to be depigmenting agents; 35% of the surveyed population were
      found to use products with skin-bleaching properties, but only 27% stated that
      they used the products specifically for these depigmenting properties. An inquiry
      into the motivations of adolescents indicated that they know about and practice
      SL but are restricted by family, religion, and Rwandese culture. Whenever side
      effects appear, consumers opt either to stop bleaching practices for a short
      period or to switch from their commercial topical product to another one with,
      presumably, a different composition. CONCLUSIONS: Albeit that many people
      acknowledge that there are possible side effects of using preparations commonly
      used in SL, the practice is generally continued. Although it is important to
      question the rationale behind the practice of SL, it is equally important to
      develop and propose safer products.

PMID- 25774001
TI  - Case Study: Community Nursing Care Plan for a Man With Functional and
      Psychosocial Problems Following a Stroke.
AB  - PURPOSE: The study aims to use the standardized nursing process to assist a
      middle-aged man with functional and psychosocial problems following a stroke.
      DATA SOURCES: Data were obtained from interviews with the patient during primary
      care nurse consultations, electronic health record reviews, and reports from
      other professionals. To build the care plan, we used available scientific
      evidence, and we also considered a nurse-patient agreement. DATA SYNTHESIS: We
      used clinical reasoning with NANDA-I classification, the Nursing Outcomes
      Classification, and the Nursing Interventions Classification to select nursing
      diagnoses, patient outcomes, and nursing interventions. CONCLUSIONS: Psychosocial
      problems complicate the management of a patient with functional consequences
      after a stroke. This fact has high impact on people who are going through this
      process.

PMID- 25774002
TI  - Sodium Butyrate Ameliorates L-Arginine-Induced Pancreatitis and Associated
      Fibrosis in Wistar Rat: Role of Inflammation and Nitrosative Stress.
AB  - Several reports indicated that histone deacetylases (HDACs) play a crucial role
      in inflammation and fibrogenesis. Sodium butyrate (SB) is a short-chain fatty
      acid having HDAC inhibition potential. The present study aimed to evaluate the
      protective effect of SB against L-arginine (L-Arg)-induced pancreatic fibrosis in
      Wistar rats. Pancreatic fibrosis was induced by twice intraperitoneal (i.p.)
      injections of 20% L-Arg (250 mg/100 g) at 2-h interval on day 1, 4, 7, and 10,
      whereas SB (800 mg/kg/day) was administrated for 10 days. At the end of the
      study, biochemical estimations, histological alterations, DNA damage, and the
      expression of various proteins were evaluated. Posttreatment of SB decreased L
      Arg-induced oxidative and nitrosative stress, DNA damage, histological
      alterations, and fibrosis. Interestingly, posttreatment of SB significantly
      decreased the expression of alpha-smooth muscle actin, interleukin-1beta,
      inducible nitric oxide synthase, and 3-nitrotyrosine. The present study
      demonstrated that posttreatment of SB alleviates L-Arg-induced pancreatic damage
      and fibrosis in rat.

PMID- 25774003
TI  - Targeted MRI/TRUS fusion-guided biopsy in men with previous prostate biopsies
      using a novel registration software and multiparametric MRI PI-RADS scores: first
      results.
AB  - PURPOSE: To evaluate a novel system for MRI/TRUS fusion-guided biopsy for
      detection of prostate cancer (PCa) in patients with previous negative prostate
      biopsy and determine diagnostic accuracy when using the Prostate Imaging
      Reporting and Data System (PI-RADS) for multiparametric magnetic resonance
      imaging (mpMRI) as proposed by the European Society of Urogenital Radiology.
      METHODS: Thirty-nine men with clinical suspicion of PCa and history of previous
      prostate biopsy underwent mpMRI on a 3-T MRI. In total, 72 lesions were evaluated
      by the consensus of two radiologists. PI-RADS scores for each MRI sequence, the
      sum of the PI-RADS scores and the global PI-RADS were determined. MRI/TRUS fusion
      guided targeted biopsy was performed using the BioJetTM software combined with a
      transrectal ultrasound system. Image fusion was based on rigid registration. PI
      RADS scores of the dominant lesion were compared with histopathological results.
      Diagnostic accuracy was determined using receiver operating characteristic curve
      analysis. RESULTS: MRI/TRUS fusion-guided biopsy was reliable and successful for
      71 out of 72 lesions. The global PI-RADS score of the dominant lesion was
      significantly higher in patients with PCa (4.0 +/- 1.3) compared to patients with
      negative histopathology (2.6 +/- 0.8; p = 0.0006). Using a global PI-RADS score
      cut-off >=4, a sensitivity of 85 %, a specificity of 82 % and a negative
      predictive value of 92 % were achieved. CONCLUSIONS: The described fusion system
      is dependable and efficient for targeted MRI/TRUS fusion-guided biopsy. mpMRI PI
      RADS scores combined with a novel real-time MRI/TRUS fusion system facilitate
      sufficient diagnosis of PCa with high sensitivity and specificity.

PMID- 25774004
TI  - Transurethral anatomical enucleation of the prostate with Tm:YAG support
      (ThuLEP): review of the literature on a novel surgical approach in the management
      of benign prostatic enlargement.
AB  - PURPOSE: Retrograde transurethral anatomical enucleation of the prostate is
      gaining momentum as a new concept in transurethral surgery of benign prostatic
      hyperplasia. Its adaptation is boosted by the familiarity of urologists with the
      finger-assisted anatomical enucleation of the adenoma during open prostatectomy
      and the combination of this well-established concept with the minimal invasive
      characteristics of transurethral surgery. The thulium laser appears as an ideal
      energy source for such operation. In this work, current evidence on thulium laser
      assisted anatomical enucleation of the prostate (ThuLEP) is being reviewed.
      MATERIALS AND METHODS: A comprehensive literature review was performed on
      Medline, PubMed, and Cochrane databases retrieving all literature on thulium
      laser-assisted prostatectomy between 2006 and 2015. Experimental studies, review
      articles and editorial comments as well as studies on thulium laser-assisted
      approaches other than ThuLEP (i.e., ThuVEP, ThuVAP or ThuVARP) were excluded from
      the analysis. RESULTS: In total, six original articles on either surgical
      technique or clinical outcomes were retrieved. With regard to functional results,
      ThuLEP presented no significant differences toward the standard treatment
      (TURP/HoLEP) arm in two randomized controlled trials and favorable outcomes in
      available prospective cohorts. Observed morbidity was minimum and comparable with
      the rest of transurethral literature. CONCLUSIONS: ThuLEP literature is still
      very limited. Based on the available data, the approach is safe and effective,
      demonstrating favorable outcomes, comparable with the current standard treatment
      options. Further documentation of ThuLEP outcomes is necessary to define the
      optimum indications of this novel technique.

PMID- 25774005
TI  - Patient and disease-specific factors and their influence on urinary
      reconstruction choice at a referral center.
AB  - PURPOSE: To evaluate potential socioeconomic and demographic factors that may
      influence or be associated with various types of urinary reconstruction (UR)
      following a radical cystectomy (RC) accounting for existing clinical variables.
      METHODS: There were 828 patients that underwent a RC and UR between 2000 and
      2013. After excluding patients that did not meet medical or surgical criteria for
      a continent urinary reconstruction (CUR-orthotopic neobladder or continent
      catheterizable pouch), there were 714 patients available for analysis.
      Socioeconomic and demographic data along with disease-specific variables were
      recorded preoperatively and analyzed to determine a correlation with a particular
      type of UR. RESULTS: Non-continent urinary reconstruction (ileal conduit or
      cutaneous ureterostomies) and CUR accounted for 78.3 % (559/714) and 21.7 %
      (155/714) of UR following RC, respectively. On univariate analysis, younger age,
      marital status, employment status, type of insurance, ASA score, and preoperative
      glomerular filtration rate were significantly associated with CUR (p < 0.01).
      Travel distance, race, and education level were not factors for UR type.
      Additionally, there was no significant difference between males and females
      receiving a CUR. On multivariate analysis, older age [odds ratio (OR) 0.85, p <
      0.01], marital status (OR 0.28, p < 0.01), insurance status (OR 0.22, p = 0.04),
      and higher ASA score (OR 0.50, p < 0.01) remained independent predictors of those
      less likely to receive a CUR. CONCLUSION: Predictable socioeconomic and
      demographic influences exist between the choice of UR after RC. Increasing age
      corresponds to a decreasing likelihood of receiving a CUR. No significant
      difference was seen between men and women in undergoing a CUR.

PMID- 25774006
TI  - Factors that influence the outcome of open urethroplasty for pelvis fracture
      urethral defect (PFUD): an observational study from a single high-volume tertiary
      care center.
AB  - PURPOSE: To report the clinical features of pelvic fracture urethral injury
      (PFUI) and assess the real effect of factors that are believed to have adverse
      effects on delayed urethroplasty. METHODS: An observational descriptive study in
      a single urological center examined 376 male patients diagnosed with PFUI who
      underwent open urethroplasty from 2009 to 2013. Analyzed factors included patient
      age at the time of injury, etiology of PFUI, type of emergency treatment,
      concomitant injuries, length and position of stricture, type of urethroplasty and
      the outcome of surgery. Univariate and multivariate logistic regression analyses
      were applied, together with analytical statistic methods such as t test and Chi
      square test. RESULTS: The overall success rate of delayed urethroplasty was 80.6
      %. Early realignment was associated with reduced stricture length and had
      beneficial effect on delayed surgery. Concomitant rectum rupture, strictures
      longer than 1.6 cm and strictures closer than 3 cm to the bladder neck were
      indicators of poor outcome. Age, type of injury, urethral fistula and bladder
      rupture were not significant predicators of surgery outcome. Failed direct vision
      internal urethrotomy and urethroplasty had no significant influence on salvage
      operation. CONCLUSIONS: The outcome of posterior urethroplasty is affected by
      multiple factors. Early realignment has beneficial effect; while the length and
      position of stricture and its distance to bladder neck plays the key role, rectum
      rupture at the time of injury is also an indicator of poor outcome. The effect of
      other factors seems insignificant.

PMID- 25774008
TI  - "Sterile Urine" and the Presence of Bacteria.
AB  - Adult human urine is not sterile. The resident bacterial community may contribute
      to urinary health and disease in undiscovered ways. Bacterial genomic sequencing
      and expanded urine culture techniques are major complementary tools for
      scientific exploration in urologic research. 

PMID- 25774009
TI  - Cytokine-producing microglia have an altered beta-amyloid load in aged APP/PS1 Tg
      mice.
AB  - Beta-amyloid (Abeta) plaques and chronic neuroinflammation are significant
      neuropathological features of Alzheimer's disease. Microglial cells in aged
      brains have potential to produce cytokines such as TNF and IL-1 family members
      (IL-1alpha, IL-1beta, and IL-1Ra) and to phagocytose Abeta in Alzheimer's
      disease, however the inter-relationship between these processes is poorly
      understood. Here we show that % Abeta plaque load followed a sigmoidal trajectory
      with age in the neocortex of APPswe/PS1DeltaE9 Tg mice, and correlated positively
      with soluble Abeta40 and Abeta42. Abeta measures were moderately correlated with
      mRNA levels of CD11b, TNF, and IL-1Ra. Cytokine production and Abeta load were
      assessed in neocortical CD11b(+)(CD45(+)) microglia by flow cytometry. Whereas
      most microglia in aged mice produced IL-1Ra, relatively low proportions of
      microglia produced TNF, IL-1alpha, and IL-1beta. However, microglial production
      of these latter cytokines was generally increased in APP/PS1 Tg mice. Microglia
      that phagocytosed endogenously-produced Abeta were only observed in APP/PS1 Tg
      mice. Differences in phagocytic index and total Abeta load were observed in
      microglia with specific cytokine profiles. Both phagocytic index and total Abeta
      load were higher in IL-1alpha(+) and IL-1Ra(+) microglia, than microglia that did
      not produce these cytokines. In contrast, total Abeta load was lower in IL
      1beta(+) and TNF(+) microglia, compared to IL-1beta(-) and TNF(-) microglia, and
      TNF(+) microglia also had a lower phagocytic index. Using GFP bone marrow
      chimeric mice, we confirmed that the majority of neocortical CD11b(+)(CD45(+))
      microglia were resident cells (GFP(-)) in APP/PS1 Tg mice, even after selectively
      analysing CD11b(+)CD45(high) cells, which are typically considered to be
      infiltrating cells. Together, our data demonstrate that cytokine expression is
      selectively correlated with age and Abeta pathology, and is associated with an
      altered Abeta load in phagocytic microglia from APP/PS1 Tg mice. These findings
      have implications for understanding the regulation of microglial cytokine
      production and phagocytosis of Abeta in Alzheimer's disease. 

PMID- 25774007
TI  - Biomarker development for presymptomatic molecular diagnosis of preeclampsia:
      feasible, useful or even unnecessary?
AB  - The past decade saw the advent of a number of promising biomarkers to detect
      pregnancies at risk for preeclampsia (PE), the foremost being those associated
      with an imbalance of angiogenic factors. In late pregnancy, these are useful for
      the detection of imminent cases of PE, while earlier they were more predictive
      for early- than late-onset PE. This suggests that there may be fundamental
      differences between the underlying pathology of these two PE forms. Therefore, it
      is possible that such a biological premise may limit the development of
      biomarkers that will permit the efficacious detection of both early- and late
      onset PE via an analysis of first-trimester maternal blood samples. Consequently,
      a significant increase in our understanding of the underlying pathology of PE,
      using a variety of approaches ranging from systems biology to animal models, will
      be necessary in order to overcome this obstacle. 

PMID- 25774010
TI  - (+)-Naltrexone is neuroprotective and promotes alternative activation in the
      mouse hippocampus after cardiac arrest/cardiopulmonary resuscitation.
AB  - Despite dramatic improvement in cardiopulmonary resuscitation (CPR) and other
      techniques for cardiac arrest (CA), the majority of survivors continue to show
      signs of decreased memory or executive cognitive function. Such memory impairment
      may be due to hippocampal CA1 neuronal death, which is delayed by several days
      after CA/CPR. Classical microgliosis in the CA1 region may contribute to neuronal
      death, yet the role of a key activation receptor Toll Like Receptor 4 (TLR4) has
      not been previously investigated for such neuronal death after CA/CPR. We show
      that (+)-naltrexone was neuroprotective after CA/CPR. TLR4 blockade was
      associated with decreased expression of markers for microglial/macrophage
      activation and T cell and B cell infiltration, as well as decreased pro
      inflammatory cytokine levels. Notably, IL-10 expression was elevated in response
      to CA/CPR, but was not attenuated by (+)-naltrexone, suggesting that the local
      monocyte/microglial phenotype had shifted towards alternative activation. This
      was confirmed by elevated expression of Arginase-1, and decreased expression of
      NFkappaB p65 subunit. Thus, (+)-naltrexone and other TLR4 antagonists may
      represent a novel therapeutic strategy to alleviate the substantial burden of
      memory or executive cognitive function impairment after CA/CPR. 

PMID- 25774011
TI  - Productivity and quality of Dutch hospitals during system reform.
AB  - This study addresses the productivity of Dutch hospitals since the start of the
      health systems reform in 2005. We consider DEA based measures, which include
      efficiency and quality for the complete set of Dutch hospitals and present cross
      sectional and longitudinal analysis. In particular, we consider how hospital
      efficiency has developed. As the reform created an environment of regulated
      competition, we pay special attention to relative efficiency. Our results suggest
      that the differences in efficiency among hospitals have become larger. In the
      years 2009-2010, the number of hospitals identified as (close to) efficient by
      DEA analysis decreased. 

PMID- 25774012
TI  - Low recurrence rates for in situ and invasive melanomas using Mohs micrographic
      surgery with melanoma antigen recognized by T cells 1 (MART-1) immunostaining:
      tissue processing methodology to optimize pathologic staging and margin
      assessment.
AB  - BACKGROUND: Various methods of tissue processing have been used to treat melanoma
      with Mohs micrographic surgery (MMS). OBJECTIVE: We describe a method of treating
      melanoma with MMS that combines breadloaf frozen sectioning of the central
      debulking excision with complete peripheral and deep microscopic margin
      evaluation, allowing detection of upstaging and comprehensive pathologic margin
      assessment before reconstruction. METHODS: We conducted a retrospective cohort
      study evaluating for local recurrence and upstaging in 614 invasive or in situ
      melanomas in 577 patients treated with this MMS tissue processing methodology
      using frozen sections with melanoma antigen recognized by T cells 1 (MART-1)
      immunostaining. Follow-up was available in 597 melanomas in 563 patients.
      RESULTS: Local recurrence was identified in 0.34% (2/597) lesions with a mean
      follow-up time of 1026 days (2.8 years). Upstaging occurred in 34 of 614 lesions
      (5.5%), of which 97% (33/34) were detected by the Mohs surgeon before
      reconstruction. LIMITATIONS: Limitations include retrospective study,
      intermediate follow-up time, and that the recurrence status of 39.6% of patients
      was self-reported. CONCLUSION: Treating melanoma with MMS that combines breadloaf
      sectioning of the central debulking excision with complete peripheral and deep
      microscopic margin evaluation permits identification of upstaging and
      consideration of sentinel lymph node biopsy before definitive reconstruction and
      achieves low local recurrence rates compared with conventional excision.

PMID- 25774013
TI  - Age, gender, and topography influence the clinical and dermoscopic appearance of
      lentigo maligna.
AB  - BACKGROUND: Little is known about the frequency of clinical and dermoscopic
      patterns of lentigo maligna (LM) in relation to specific anatomic subsites and
      patients characteristics. OBJECTIVE: We sought to assess the frequency of
      clinical and dermoscopic features of LM and to correlate them to specific
      anatomic subsites, and patients' age and gender. METHODS: This was a
      retrospective analysis of clinical and dermoscopic images of a series of
      consecutive, histopathologically diagnosed, facial and extrafacial LM. RESULTS: A
      total of 201 cases from 200 patients (mean age 69.51 +/- 12.26 years) including
      120 women were collected. Most cases were located on the face (n = 192, 95.5%).
      In 102 cases, LM presented as clinically solitary facial macule (s/LM), whereas
      it was associated with multiple surrounding freckles in the remaining cases. s/LM
      were significantly smaller (<10 vs >10 mm; P = .020) and associated with younger
      age compared with LM associated with multiple surrounding freckles (mean age
      67.73 +/- 12.68 years vs 71.34 +/- 11.59 years, respectively; P = .036).
      Dermoscopically, gray color irrespective of a specific pattern was the most
      prevalent finding seen in 178 (88.6%) cases. LIMITATIONS: This was a
      retrospective study. CONCLUSIONS: The knowledge about patient age, patient
      gender, and site-related clinical features of LM associated with gray color upon
      dermoscopy may enhance the clinical recognition of LM.

PMID- 25774014
TI  - A hypomorphic allele reveals an important role of inturned in mouse skeletal
      development.
AB  - BACKGROUND: Cilia are important for Hedgehog signaling in vertebrates and many
      genes that encode proteins involved in ciliogenesis have been studied for their
      roles in embryonic development. Null mutations in many of these genes cause early
      embryonic lethality, hence an understanding of their roles in postnatal
      development is limited. RESULTS: The Inturned (Intu) gene is required for
      ciliogenesis and here we report a recessive hypomorphic mutation, resulting in
      substitution of a conserved hydrophobic residue (I813N) near the C-terminus, that
      sheds light on later functions of Intu. Mice homozygous for this Double-thumb
      (Intu(Dtm)) allele exhibit polydactyly, retarded growth, and reduced survival.
      There is a moderate loss of cilia in Intu(Dtm/Dtm) mutants, and Intu(I813N)
      exhibits compromised ability to increase ciliogenesis in cultured Intu null
      mutant cells. Intu(Dtm) mutants show rib defects and delay of endochondral
      ossification in long bones, digits, vertebrae, and the sternum. These skeletal
      defects correlate with a decrease in Hh signaling. However, patterning of the
      neural tube and planar cell polarity appear to be normal. CONCLUSIONS: This
      hypomorphic Intu allele highlights an important role of Intu in mouse skeletal
      development.

PMID- 25774015
TI  - Cost Effectiveness of Preventive Treatment for Tuberculosis in Special High-Risk
      Populations.
AB  - OBJECTIVE: In view of the goal of eliminating tuberculosis (TB) by 2050, economic
      evaluations of interventions against the development of TB are increasingly
      requested. Little research has been published on the incremental cost
      effectiveness of preventative therapy (PT) in groups at high risk for progression
      from latent TB infection (LTBI) with Mycobacterium TB (MTB) to active disease. A
      systematic review of studies with a primary focus on model-driving inputs and
      methodological differences was conducted. METHODS: A search of MEDLINE, the
      Cochrane Library and EMBASE to July 2014 was undertaken, and reference lists of
      eligible articles and relevant reviews were examined. RESULTS: A total of 876
      citations were retrieved, with a total of 24 studies being eligible for
      inclusion, addressing six high-risk groups other than contact persons. Results
      varied considerably between studies and countries, and also over time. Although
      the selected studies generally demonstrated cost effectiveness for PT in HIV
      infected subjects and healthcare workers (HCWs), the outcome of these analyses
      can be questioned in light of recent epidemiologic data. For immigrants from high
      TB-burden countries, patients with end-stage renal disease, and the
      immunosuppressed, now defined as further vulnerable groups, no consistent
      recommendation can be taken from the literature with respect to cost
      effectiveness of screening and treating LTBI. When the concept of a fixed
      willingness-to-pay (WTP) threshold as a prerequisite for final categorization was
      used, the sums ranged between 'no specification' and US$100,000 per quality
      adjusted life-year. CONCLUSIONS: To date, incremental cost-effectiveness analyses
      on PT in groups at high risk for TB progression, other than contacts, are
      surprisingly scarce. The variation found between studies likely reflects
      variations in the major epidemiologic factors, particularly in the estimates on
      the accuracy of the tuberculin skin test (TST) and interferon-gamma release
      assays (IGRA) as screening methods used before considering PT. Further research,
      including explicit evaluation of local epidemiological conditions, test accuracy,
      and methodology of WTP thresholds, is needed.

PMID- 25774016
TI  - Cost-utility analysis of intravenous immunoglobulin for the treatment of steroid
      refractory dermatomyositis in Thailand.
AB  - INTRODUCTION: Intravenous immunoglobulin (IVIG) has been shown to be effective in
      treating steroid-refractory dermatomyositis (DM). There remains no evidence of
      its cost-effectiveness in Thailand. OBJECTIVE: Our objective was to estimate the
      cost utility of IVIG as a second-line therapy in steroid-refractory DM in
      Thailand. METHODS: A Markov model was developed to estimate the relevant costs
      and health benefits for IVIG plus corticosteroids in comparison with
      immunosuppressant plus corticosteroids in steroid-refractory DM from a societal
      perspective over a patient's lifetime. The effectiveness and utility parameters
      were obtained from clinical literature, meta-analyses, medical record reviews,
      and patient interviews, whereas cost data were obtained from an electronic
      hospital database and patient interviews. Costs are presented in $US, year 2012
      values. All future costs and outcomes were discounted at a rate of 3% per annum.
      One-way and probabilistic sensitivity analyses were also performed. RESULTS: Over
      a lifetime horizon, the model estimated treatment under IVIG plus corticosteroids
      to be cost saving compared with immunosuppressant plus corticosteroids, where the
      saving of costs and incremental quality-adjusted life-years (QALYs) were
      $US4738.92 and 1.96 QALYs, respectively. Sensitivity analyses revealed that
      probability of response of immunosuppressant plus corticosteroids was the most
      influential parameter on incremental QALYs and costs. At a societal willingness
      to-pay threshold in Thailand of $US5148 per QALY gained, the probability of IVIG
      being cost effective was 97.6%. CONCLUSIONS: The use of IVIG plus corticosteroids
      is cost saving compared with treatment with immunosuppressant plus
      corticosteroids in Thai patients with steroid-refractory DM. Policy makers should
      consider using our findings in their decision-making process for adding IVIG to
      corticosteroids as the second-line therapy for steroid-refractory DM patients.

PMID- 25774017
TI  - Cost-utility analysis of a medication review with follow-up service for older
      adults with polypharmacy in community pharmacies in Spain: the conSIGUE program.
AB  - BACKGROUND: The concept of pharmaceutical care is operationalized through
      pharmaceutical professional services, which are patient-oriented to optimize
      their pharmacotherapy and to improve clinical outcomes. OBJECTIVE: The objective
      of this study was to estimate the incremental cost-effectiveness ratio (ICER) of
      a medication review with follow-up (MRF) service for older adults with
      polypharmacy in Spanish community pharmacies against the alternative of having
      their medication dispensed normally. METHODS: The study was designed as a cluster
      randomized controlled trial, and was carried out over a time horizon of 6 months.
      The target population was older adults with polypharmacy, defined as individuals
      taking five or more medicines per day. The study was conducted in 178 community
      pharmacies in Spain. Cost-utility analysis adopted a health service perspective.
      Costs were in euros at 2014 prices and the effectiveness of the intervention was
      estimated as quality-adjusted life-years (QALYs). In order to analyze the
      uncertainty of ICER results, we performed a non-parametric bootstrapping with
      5000 replications. RESULTS: A total of 1403 older adults, aged between 65 and 94
      years, were enrolled in the study: 688 in the intervention group (IG) and 715 in
      the control group (CG). By the end of the follow-up, both groups had reduced the
      mean number of prescribed medications they took, although this reduction was
      greater in the IG (0.28 +/- 1.25 drugs; p < 0.001) than in the CG (0.07 +/- 0.95
      drugs; p = 0.063). Older adults in the IG saw their quality of life improved by
      0.0528 +/- 0.20 (p < 0.001). In contrast, the CG experienced a slight reduction
      in their quality of life: 0.0022 +/- 0.24 (p = 0.815). The mean total cost was
      <euro>977.57 +/- 1455.88 for the IG and <euro>1173.44 +/- 3671.65 for the CG. In
      order to estimate the ICER, we used the costs adjusted for baseline medications
      and QALYs adjusted for baseline utility score, resulting in a mean incremental
      total cost of -<euro>250.51 +/- 148.61 (95 % CI -541.79 to 40.76) and a mean
      incremental QALY of 0.0156 +/- 0.004 (95 % CI 0.008-0.023). Regarding the results
      from the cost-utility analysis, the MRF service emerged as the dominant strategy.
      CONCLUSION: The MRF service is an effective intervention for optimizing
      prescribed medication and improving quality of life in older adults with
      polypharmacy in community pharmacies. The results from the cost-utility analysis
      suggest that the MRF service is cost effective.

PMID- 25774018
TI  - Systematic review of medical home models to promote transitions to primary adult
      health care for adolescents living with autism spectrum disorder.
AB  - BACKGROUND: There is a growing number of children diagnosed and living with
      autism spectrum disorders (ASDs) in the United States. This increasing incidence
      and prevalence of ASDs require care coordination within a medical home model,
      which needs to continue into adulthood. AIM: This paper is an evidence review of
      medical home models for transitioning adolescents living with ASDs from pediatric
      primary healthcare practices to adult primary care practices. METHOD: Databases
      were reviewed and articles selected based on inclusion and exclusion criteria.
      RESULTS: Nine articles were reviewed and four met criteria. None of the articles
      addressed medical home models to transition adolescents living with ASDs into
      adult primary healthcare services. LINKING EVIDENCE TO ACTION: There is a need
      for nursing to work within an interdisciplinary framework to educate adult
      healthcare providers on the needs of adolescents living with ASDs and to evaluate
      medical home transition models for this vulnerable population.

PMID- 25774019
TI  - [How to write a good clinical review?].
AB  - Clinical reviews are an important part of the medical literature offering the
      reader condensed information on a specific topic. In radiology and nuclear
      medicine most clinical reviews have a subjective character as they have been
      written in a rather narrative way. Based on their low level of evidence these
      narrative reviews are frequently not being considered for establishment of
      clinical guidelines. The aim of this paper is to aid the reader in writing a good
      clinical review by highlighting the different aspects of a systematic review. 

PMID- 25774020
TI  - Cell Cycle-Dependent Localization of Dynactin Subunit p150 glued at Centrosome.
AB  - p150(glued) is the largest subunit of dynactin protein complex, through which
      cargo vesicles link to the microtubule minus-end directed motor protein dynein.
      In addition, p150(glued) also locates in the mother centriole where it organizes
      the subdistal appendage. The components of appendage are dynamically regulated
      throughout the cell cycle stages, but it is still unclear whether the centrosomal
      residency of p150(glued) correlated with cell cycle progression. Here we found
      that p150(glued) was located in the mother centriole during G1/S stage and its
      centrosomal residency was independent of microtubule transportation. However, the
      centrosomal p150(glued) became blurred at G2/M phase and this event was not
      regulated by its phosphorylation. Entering into mitosis, p150(glued) was robustly
      enriched in the mitotic spindle nearby the spindle poles but not in the
      centrosome. During serum starvation (G0 stage), p150(glued) appeared at the base
      of primary cilium and its depletion attenuated starvation-induced primary cilium
      formation. We also checked its role in the maintenance of centrosome homeostasis
      and configuration, and found depletion of p150(glued) did not induce centrosome
      amplification or splitting but inhibited U2OS cell growth. G1 arrest and reduced
      EdU incorporation were observed in p150(glued) deficient U2OS cells. In addition,
      cyclin E was downregulated following p150(glued) depletion. The p53/p21 signaling
      was activated indicating that CDKs were inactivated. The reduced cell growth was
      ameliorated in the p150(glued) depleted cells when treated with p53 inhibitor.
      Thus, we have identified the centrosomal targeting of p150(glued) in distinct
      cell cycle stage and uncovered its role in controlling G1/S transition.

PMID- 25774021
TI  - Thermal responses and perceptions under distinct ambient temperature and wind
      conditions.
AB  - Wind conditions are widely recognized to influence the thermal states of humans.
      In this study, we investigated the relationship between wind conditions and
      thermal perception and energy balance in humans. The study participants were
      exposed for 20 min to 3 distinct ambient temperatures, wind speeds, and wind
      angles. During the exposure, the skin temperatures as a physiological reaction
      and mental reactions of the human body were measured and the energy balance was
      calculated based on the human thermal-load method. The results indicate that the
      human thermal load is an accurate indicator of human thermal states under all
      wind conditions. Furthermore, wind speed and direction by themselves do not
      account for the human thermal experience. Because of the thermoregulation that
      occurs to prevent heat loss and protect the core of the body, a low skin
      temperature was maintained and regional differences in skin temperature were
      detected under cool ambient conditions. Thus, the human thermal load, which
      represents physiological parameters such as skin-temperature change, adequately
      describes the mixed sensation of the human thermal experience.

PMID- 25774022
TI  - Age-related alterations in the central thermoregulatory responsiveness to alpha
      MSH.
AB  - Alpha-melanocyte-stimulating-hormone (alpha-MSH) is a neuropeptide that induces
      weight loss via its anorexigenic and hypermetabolic/hyperthermic effects. Two
      major public health problems of the human population involving energy balance
      (i.e. middle-aged obesity and aging cachexia) also appear in other mammals,
      therefore age-related regulatory alterations may also be assumed in the
      background. Previous studies demonstrated characteristic age-related shifts in
      the anorexigenic effects of centrally applied alpha-MSH with strong effects in
      young adult, diminished efficacy in middle-aged and very pronounced
      responsiveness in old rats. The present study aimed to investigate age-related
      changes in the acute central thermoregulatory responsiveness to an alpha-MSH
      injection in rats and to compare them with those of food intake-related
      responsiveness. Oxygen consumption (VO2), core (Tc) and tail skin temperatures
      (Ts, indicating heat loss) of male Wistar rats of different age groups (from 2 to
      24 months of age), were recorded in an indirect calorimeter complemented by
      thermocouples upon intracerebroventricular alpha-MSH administration (0, 5 ug) at
      a slightly subthermoneutral environment (25-26  degrees C). Acute alpha-MSH
      induced rises in VO2 and Tc were most pronounced in the young adult age-group. In
      these rats the hyperthemic effects were somewhat diminished by an activation of
      heat loss. Juvenile animals showed weaker hyperthermic responses, middle-aged
      rats none at all. Alpha-MSH-induced hyperthermia became significant again in old
      rats. Acute thermoregulatory (hypermetabolic/hyperthermic) responsiveness to
      alpha-MSH shows a distinct age-related pattern similar to that of acute
      anorexigenic responsiveness. Thus, our results may also contribute to the
      explanation of both middle-aged obesity and aging cachexia.

PMID- 25774023
TI  - Meta-analysis of the effects of microclimate cooling systems on human performance
      under thermal stressful environments: potential applications to occupational
      workers.
AB  - This study aims to determine the appropriate microclimate cooling systems (MCSs)
      to reduce heat stress and improve human performance of occupational workers and
      their practicality in the occupational field. Meta-analysis was employed to
      summarize, analyze, and compare the effects of various MCSs on human performance
      with corresponding physiological and psychological responses, thereby providing
      solid suggestions for selecting suitable MCSs for occupational workers. Wearing
      MCSs significantly attenuated the increases in core temperature (-0.34  degrees
      C/h) and sweating rate (-0.30 L/h), and significantly improved human performance
      (+29.9%, effect size [EFS] = 1.1) compared with no cooling condition (CON). Cold
      air-cooled garments (ACG-Cs; +106.2%, EFS = 2.32) exhibited greater effects on
      improving human performance among various microclimate cooling garments (MCGs),
      followed by liquid cooling garments (LCGs; +68.1%, EFS = 1.86) and hybrid cooling
      garment combining air and liquid cooling (HBCG-AL; +59.1%, EFS=3.38), natural air
      cooled garments (ACG-Ns; +39.9%, EFS = 1.12), and phase change material cooling
      garments (PCMCGs; +19.5%, EFS = 1.2). Performance improvement was observed to be
      positively and linearly correlated to the differences of core temperature
      increase rate (r = 0.65, p < 0.01) and sweating rate (r = 0.80, p < 0.001)
      between MCSs and CON. Considering their application in industrial settings, ACG
      Cs, LCGs, and HBCG-AL are practical for work, in which workers do not move
      frequently, whereas ACG-Ns and PCMCGs are more applicable for the majority of
      occupational workers. Further enhancement of the cooling efficiency of these two
      cooling strategies should be initiated.

PMID- 25774024
TI  - The effect of using different regions of interest on local and mean skin
      temperature.
AB  - The dynamic nature of tissue temperature and the subcutaneous properties, such as
      blood flow, fatness, and metabolic rate, leads to variation in local skin
      temperature. Therefore, we investigated the effects of using multiple regions of
      interest when calculating weighted mean skin temperature from four local sites.
      Twenty-six healthy males completed a single trial in a thermonetural laboratory
      (mean +/- SD): 24.0 (1.2) degrees C; 56 (8%) relative humidity; <0.1 m/s air
      speed). Mean skin temperature was calculated from four local sites (neck,
      scapula, hand and shin) in accordance with International Standards using digital
      infrared thermography. A 50 mm * 50 mm, defined by strips of aluminium tape,
      created six unique regions of interest, top left quadrant, top right quadrant,
      bottom left quadrant, bottom right quadrant, centre quadrant and the entire
      region of interest, at each of the local sites. The largest potential error in
      weighted mean skin temperature was calculated using a combination of a) the
      coolest and b) the warmest regions of interest at each of the local sites.
      Significant differences between the six regions interest were observed at the
      neck (P<0.01), scapula (P<0.001) and shin (P<0.05); but not at the hand (P =
      0.482). The largest difference (+/- SEM) at each site was as follows: neck 0.2
      (0.1) degrees C; scapula 0.2 (0.0) degrees C; shin 0.1 (0.0) degrees C and hand
      0.1 (0.1) degrees C. The largest potential error (mean +/- SD) in weighted mean
      skin temperature was 0.4 (0.1) degrees C (P<0.001) and the associated 95% limits
      of agreement for these differences was 0.2-0.5  degrees C. Although we observed
      differences in local and mean skin temperature based on the region of interest
      employed, these differences were minimal and are not considered physiologically
      meaningful.

PMID- 25774025
TI  - Effects of normobaric hypoxic bed rest on the thermal comfort zone.
AB  - Future Lunar and Mars habitats will maintain a hypobaric hypoxic environment to
      minimise the risk of decompression sickness during the preparation for extra
      vehicular activity. This study was part of a larger study investigating the
      separate and combined effects of inactivity associated with reduced gravity and
      hypoxia, on the cardiovascular, musculoskeletal, neurohumoural, and
      thermoregulatory systems. Eleven healthy normothermic young male subjects
      participated in three trials conducted on separate occasions: (1) Normobaric
      hypoxic ambulatory confinement, (2) Normobaric hypoxic bedrest and (3) Normobaric
      normoxic bedrest. Normobaric hypoxia was achieved by reduction of the oxygen
      fraction in the air (FiO2 = 0.141 +/- 0.004) within the facility, while the
      effects of reduced gravity were simulated by confining the subjects to a
      horizontal position in bed, with all daily routines performed in this position
      for 21 days. The present study investigated the effect of the interventions on
      behavioural temperature regulation. The characteristics of the thermal comfort
      zone (TCZ) were assessed by a water-perfused suit, with the subjects instructed
      to regulate the sinusoidally varying temperature of the suit within a range
      considered as thermally comfortable. Measurements were performed 5 days prior to
      the intervention (D-5), and on days 10 (D10) and 20 (D20) of the intervention. no
      statistically significant differences were found in any of the characteristics of
      the TCZ between the interventions (HAMB, HBR and NBR), or between different
      measurement days (D-5, D10, D20) within each intervention. rectal temperature
      remained stable, whereas skin temperature (Tsk) increased during all
      interventions throughout the one hour trial. no difference in Tsk between D-5,
      D10 and D20, and between HAMB, HBR and NBR were revealed. subjects perceived the
      regulated temperature as thermally comfortable, and neutral or warm. we conclude
      that regulation of thermal comfort is not compromised by hypoxic inactivity.

PMID- 25774026
TI  - Design and testing of a liquid cooled garment for hot environments.
AB  - Liquid cooled garments (LCGs) are considered a viable method to protect
      individuals from hyperthermia and heat-related illness when working in thermally
      stressful environments. While the concept of LCGs was proposed over 50 years ago,
      the design and testing of these systems is undeveloped and stands in need of
      further study. In this study, a detailed heat transfer model of LCG in a hot
      environment was built to analyze the effects of different factors on the LCG
      performance, and to identify the main limitations to achieve maximum performance.
      An LCG prototype was designed and fabricated. Series of tests were done by a
      modified thermal manikin method to validate the heat transfer model and to
      evaluate the thermal properties. Both experimental and predicted results show
      that the heat flux components match the heat balance equation with an error of
      less than 10% at different flowrate. Thermal resistance analysis also manifests
      that the thermal resistance between the cooling water and the ambient (R2) is
      more sensitive to the flowrate than to the one between the skin surface and the
      cooling water (R1). When the flowrate increased from 225 to 544 mL/min, R2
      decreased from 0.5 to 0.3  degrees C m(2)/W while R1 almost remained constant. A
      specific duration time was proposed to assess the durability and an optimized
      value of 1.68 h/kg was found according to the heat transfer model. The present
      heat transfer model and specific duration time concept could be used to optimize
      and evaluate this kind of LCG respectively.

PMID- 25774027
TI  - Isothermic and fixed intensity heat acclimation methods induce similar heat
      adaptation following short and long-term timescales.
AB  - Heat acclimation requires the interaction between hot environments and exercise
      to elicit thermoregulatory adaptations. Optimal synergism between these
      parameters is unknown. Common practise involves utilising a fixed workload model
      where exercise prescription is controlled and core temperature is uncontrolled,
      or an isothermic model where core temperature is controlled and work rate is
      manipulated to control core temperature. Following a baseline heat stress test;
      24 males performed a between groups experimental design performing short term
      heat acclimation (STHA; five 90 min sessions) and long term heat acclimation
      (LTHA; STHA plus further five 90 min sessions) utilising either fixed intensity
      (50% VO2peak), continuous isothermic (target rectal temperature 38.5  degrees C
      for STHA and LTHA), or progressive isothermic heat acclimation (target rectal
      temperature 38.5  degrees C for STHA, and 39.0  degrees C for LTHA). Identical
      heat stress tests followed STHA and LTHA to determine the magnitude of
      adaptation. All methods induced equal adaptation from baseline however isothermic
      methods induced adaptation and reduced exercise durations (STHA = -66% and LTHA =
      -72%) and mean session intensity (STHA = -13% VO2peak and LTHA = -9% VO2peak) in
      comparison to fixed (p < 0.05). STHA decreased exercising heart rate (-10 b min(
      1)), core (-0.2  degrees C) and skin temperature (-0.51  degrees C), with sweat
      losses increasing (+0.36 Lh(-1)) (p<0.05). No difference between heat acclimation
      methods, and no further benefit of LTHA was observed (p > 0.05). Only thermal
      sensation improved from baseline to STHA (-0.2), and then between STHA and LTHA (
      0.5) (p<0.05). Both the continuous and progressive isothermic methods elicited
      exercise duration, mean session intensity, and mean T(rec) analogous to more
      efficient administration for maximising adaptation. Short term isothermic methods
      are therefore optimal for individuals aiming to achieve heat adaptation most
      economically, i.e. when integrating heat acclimation into a pre-competition
      taper. Fixed methods may be optimal for military and occupational applications
      due to lower exercise intensity and simplified administration.

PMID- 25774028
TI  - Effect of nesting environment on incubation temperature and hatching success of
      Morelet's crocodile (Crocodylus moreletii) in an urban lake of Southeastern
      Mexico.
AB  - Incubation temperature is an important aspect in terms of biological performance
      among crocodiles, and several controlled experiments have demonstrated a
      significant relationship between incubation temperature, success in hatching and
      survival of hatchlings. However, a few studies have tested these relationships in
      the wild. The objective of this study was to determine the relationship of nest
      characteristics and environment (hatch year, nest basal area and height, clutch
      size, distance to shore line, and vegetation cover), to incubation temperature
      and hatching success among Morelet's crocodile (Crocodylus moreletii). The study
      was carried out during the nesting seasons of Morelet's crocodile, from 2007 to
      2009 in the Laguna de Las Ilusiones, an urban lake located in Villahermosa,
      Tabasco, Mexico. We physically characterized 18 nests and inserted a temperature
      data logger in each nest chamber. At the end of the nesting season and prior to
      hatching, we recovered the crocodile eggs and data loggers and calculated
      hatching success, under laboratory conditions. We related the environmental
      variables of the nest with the mean and fluctuation (standard deviation) of nest
      temperature, using linear models. We also related the environmental variables
      affecting the nest, to mean nest temperature and fluctuation in incubation
      temperature and to hatching success, using linear models. Although we found
      differences in incubation temperature between nests, mean incubation temperature
      did not differ between years, but there were differences in nest thermal
      fluctuation between years. The mean incubation temperature for 11 nests (61.1%)
      was lower than the suggested Female-Male pivotal temperature (producing 50% of
      each sex) for this species, and all hatchlings obtained were males. There were no
      differences in clutch size between years, but hatching success varied. Our study
      indicates that hatching success depends on certain environmental variables and
      nest conditions to which the eggs are subjected, including season, nest size and
      clutch size. We also discuss the importance of the fluctuation of incubation
      temperature on hatching success and sex determination. 

PMID- 25774029
TI  - A comparative study of thermal effects of 3 types of laser in eye: 3D simulation
      with bioheat equation.
AB  - The application of laser in ophthalmology and eye surgery is so widespread that
      hardly can anyone deny its importance. On the other hand, since the human eye is
      an organ susceptible to external factors such as heat waves, laser radiation
      rapidly increases the temperature of the eye and therefore the study of
      temperature distribution inside the eye under laser irradiation is crucial; but
      the use of experimental and invasive methods for measuring the temperature inside
      the eye is typically high-risk and hazardous. In this paper, using the three
      dimensional finite element method, the distribution of heat transfer inside the
      eye under transient condition was studied through three different lasers named
      Nd:Yag, Nd:Yap and ArF. Considering the metabolic heat and blood perfusion rate
      in various regions of the eye, numerical solution of space-time dependant Pennes
      bioheat transfer equation has been applied in this study. Lambert-Beer's law has
      been used to model the absorption of laser energy inside the eye tissues. It
      should also be mentioned that the effect of the ambient temperature, tear
      evaporation rate, laser power and the pupil diameter on the temperature
      distribution have been studied. Also, temperature distribution inside the eye
      after applying each laser and temperature variations of six optional regions as
      functions of time have been investigated. The results show that these radiations
      cause temperature rise in various regions, which will in turn causes serious
      damages to the eye tissues. Investigating the temperature distribution inside the
      eye under the laser irradiation can be a useful tool to study and predict the
      thermal effects of laser radiation on the human eye and evaluate the risk
      involved in performing laser surgery. 

PMID- 25774030
TI  - Behavioural adaptations of Rana temporaria to cold climates.
AB  - Environmental conditions at the edge of a species' ecological optimum can exert
      great ecological or evolutionary pressure at local populations. For ectotherms
      like amphibians temperature is one of the most important abiotic factors of their
      environment as it influences directly their metabolism and sets limits to their
      distribution. Amphibians have evolved three ways to cope with sub-zero
      temperatures: freeze tolerance, freeze protection, freeze avoidance. The aim of
      this study was to assess which strategy common frogs at mid and high elevation
      use to survive and thrive in cold climates. In particular we (1) tested for the
      presence of physiological freeze protection, (2) evaluated autumnal activity and
      overwintering behaviour with respect to freeze avoidance and (3) assessed the
      importance of different high-elevation microhabitats for behavioural
      thermoregulation. Common frogs did not exhibit any signs of freeze protection
      when experiencing temperatures around 0  degrees C. Instead they retreated to
      open water for protection and overwintering. High elevation common frogs remained
      active for around the same period of time than their conspecifics at lower
      elevation. Our results suggest that at mid and high elevation common frogs use
      freeze avoidance alone to survive temperatures below 0  degrees C. The
      availability of warm microhabitats, such as rock or pasture, provides high
      elevation frogs with the opportunity of behavioural thermoregulation and thus
      allows them to remain active at temperatures at which common frogs at lower
      elevation cease activity.

PMID- 25774031
TI  - Repeatability of a running heat tolerance test.
AB  - At present there is no standardised heat tolerance test (HTT) procedure adopting
      a running mode of exercise. Current HTTs may misdiagnose a runner's
      susceptibility to a hyperthermic state due to differences in exercise intensity.
      The current study aimed to establish the repeatability of a practical running
      test to evaluate individual's ability to tolerate exercise heat stress. Sixteen
      (8M, 8F) participants performed the running HTT (RHTT) (30 min, 9 km h(-1), 2%
      elevation) on two separate occasions in a hot environment (40  degrees C and 40%
      relative humidity). There were no differences in peak rectal temperature (RHTT1:
      38.82 +/- 0.47  degrees C, RHTT2: 38.86 +/- 0.49  degrees C, Intra-class
      correlation coefficient (ICC)=0.93, typical error of measure (TEM) = 0.13 
      degrees C), peak skin temperature (RHTT1: 38.12 +/- 0.45, RHTT2: 38.11 +/- 0.45 
      degrees C, ICC = 0.79, TEM = 0.30  degrees C), peak heart rate (RHTT1: 182 +/- 15
      beats min(-1), RHTT2: 183 +/- 15 beats min(-1), ICC = 0.99, TEM = 2 beats min(
      1)), nor sweat rate (1721 +/- 675 g h(-1), 1716 +/- 745 g h(-1), ICC = 0.95, TEM
      = 162 g h(-1)) between RHTT1 and RHTT2 (p>0.05). Results demonstrate good
      agreement, strong correlations and small differences between repeated trials, and
      the TEM values suggest low within-participant variability. The RHTT was effective
      in differentiating between individuals physiological responses; supporting a heat
      tolerance continuum. The findings suggest the RHTT is a repeatable measure of
      physiological strain in the heat and may be used to assess the effectiveness of
      acute and chronic heat alleviating procedures.

PMID- 25774032
TI  - A numerical study on dual-phase-lag model of bio-heat transfer during
      hyperthermia treatment.
AB  - The success of hyperthermia in the treatment of cancer depends on the precise
      prediction and control of temperature. It was absolutely a necessity for
      hyperthermia treatment planning to understand the temperature distribution within
      living biological tissues. In this paper, dual-phase-lag model of bio-heat
      transfer has been studied using Gaussian distribution source term under most
      generalized boundary condition during hyperthermia treatment. An approximate
      analytical solution of the present problem has been done by Finite element
      wavelet Galerkin method which uses Legendre wavelet as a basis function. Multi
      resolution analysis of Legendre wavelet in the present case localizes small scale
      variations of solution and fast switching of functional bases. The whole analysis
      is presented in dimensionless form. The dual-phase-lag model of bio-heat transfer
      has compared with Pennes and Thermal wave model of bio-heat transfer and it has
      been found that large differences in the temperature at the hyperthermia position
      and time to achieve the hyperthermia temperature exist, when we increase the
      value of tauT. Particular cases when surface subjected to boundary condition of
      1st, 2nd and 3rd kind are discussed in detail. The use of dual-phase-lag model of
      bio-heat transfer and finite element wavelet Galerkin method as a solution method
      helps in precise prediction of temperature. Gaussian distribution source term
      helps in control of temperature during hyperthermia treatment. So, it makes this
      study more useful for clinical applications. 

PMID- 25774033
TI  - Extreme operative temperatures are better descriptors of the thermal environment
      than mean temperatures.
AB  - In ecological studies of thermal biology the thermal environment is most
      frequently described using the mean or other measures of central tendency in
      environmental temperatures. However, this procedure may hide biologically
      relevant thermal variation for ectotherms, potentially misleading
      interpretations. Extremes of operative temperatures (EOT) can help with this
      problem by bracketing the thermal environment of focal animals. Within this
      paper, we quantify how mean operative temperatures relate to the range of
      simultaneously available operative temperatures (a measure of error). We also
      show how EOT: 1) detect more thermal differences among microsites than measures
      of central tendency, like the mean OT, 2) allow inferring on microsite use by
      ectothermic animals, and 3) clarify the relationships between field operative
      temperatures and temperatures measured at weather stations (WS). To do that, we
      explored operative temperatures measured at four sites of the Brazilian Caatingas
      and their correspondent nearest weather stations. We found that the daily mean OT
      can hide temperature ranges of 41  degrees C simultaneously available at our
      study sites. In addition, EOT detected more thermal differences among microsites
      than central quantiles. We also show how EOT allow inferring about microsite use
      of ectothermic animals in a given site. Finally, the daily maximum temperature
      and the daily temperature range measured at WSs predicted well the minimum
      available field OT at localities many kilometers away. Based on our results, we
      recommend the use of EOT, instead of mean OT, in thermal ecology studies.

PMID- 25774034
TI  - Effects of overwintering temperature on the survival of the black garden ant
      (Lasius niger).
AB  - The overwintering temperatures of ants might well be elevated due to climate
      change. We studied whether the overwintering temperature affects the survival of
      the queens and whole colonies of the black garden ant, Lasius niger (Linnaeus,
      1758). In two consecutive years (2009, 2010) we collected mated, colony founding
      queens (n = 280) from the urban area of Turku, Finland. Half of the queens
      overwintered in +7 to +8  degrees C and the other half in +2  degrees C. After
      the overwintering period, we determined their survival rate and measured the body
      fat content, body size and immune defence (encapsulation rate) of overwintering
      queens. Using the same setup, we studied the survival of 1-year-old L. niger
      colonies (queen & workers). Overwintering at a lower temperature (+2  degrees C)
      decreased the survival of workers. The survival of colony founding queens
      differed between years, but unlike with workers, the overwintering temperature
      did not affect their survival: neither in the colony experiment nor in the single
      queen experiment. All of the surviving queens managed to produce their worker
      offspring at the same rate. The relative amount of body fat of queens was higher
      for those who overwintered at a lower temperature, which is likely a result of
      lower energy consumption. We did not detect differences in the encapsulation rate
      between the temperature treatment groups. The ability of colony founding queens
      to tolerate wide overwintering temperature variations present in urban
      environments may explain the success of the colony in urban areas. As the colony
      grows, the overwintering chambers may extend more deeply into the ground. Thus,
      workers may not have to cope with such cold conditions as colony founding queens.

PMID- 25774035
TI  - Using motion-sensor camera technology to infer seasonal activity and thermal
      niche of the desert tortoise (Gopherus agassizii).
AB  - Understanding the relationships between environmental variables and wildlife
      activity is an important part of effective management. The desert tortoise
      (Gopherus agassizii), an imperiled species of arid environments in the southwest
      US, may have increasingly restricted windows for activity due to current warming
      trends. In summer 2013, we deployed 48 motion sensor cameras at the entrances of
      tortoise burrows to investigate the effects of temperature, sex, and day of the
      year on the activity of desert tortoises. Using generalized estimating equations,
      we found that the relative probability of activity was associated with
      temperature (linear and quadratic), sex, and day of the year. Sex effects showed
      that male tortoises are generally more active than female tortoises. Temperature
      had a quadratic effect, indicating that tortoise activity was heightened at a
      range of temperatures. In addition, we found significant support for interactions
      between sex and day of the year, and sex and temperature as predictors of the
      probability of activity. Using our models, we were able to estimate air
      temperatures and times (days and hours) that were associated with maximum
      activity during the study. Because tortoise activity is constrained by
      environmental conditions such as temperature, it is increasingly vital to conduct
      studies on how tortoises vary their activity throughout the Sonoran Desert to
      better understand the effects of a changing climate. 

PMID- 25774037
TI  - Immunization Status of Young People Attending a Youth Clinic in Geneva,
      Switzerland.
AB  - Adolescent vaccination coverage is very variable in European countries and data
      are scarce. The aim of this study was to assess immunization status and analyze
      potential variations according to sociodemographic variables in a youth clinic in
      Geneva, Switzerland. Immunization status was assessed retrospectively: Tetanus
      (number of doses or in absence of data tetanus antibodies) and measles as
      indicators of childhood coverage as well as hepatitis B and human papillomavirus.
      All new patients (N = 390) of Geneva University Hospital's youth clinic were
      included between January 2010 and June 2011. Vaccine coverage was low for all
      vaccines regardless of sex or origin. 89% of young people tested (mostly recent
      immigrants with no available data) had tetanus antibodies indicating adequate
      childhood immunization but hepatitis B and HPV coverage was low especially in
      recent immigrants. Systematic assessment allows better adolescent vaccine
      coverage and can improve safety by avoiding unnecessary dosis.

PMID- 25774038
TI  - Self-Efficacy as a Mediator of the Relationship Between the Perceived Food
      Environment and Healthy Eating in a Low Income Population in Los Angeles County.
AB  - While previous studies have described psychosocial and environmental factors that
      contribute to healthy eating, much remains unknown about the interactions between
      them. We assessed the relationship between the perceived food environment, self
      efficacy and fruit and vegetable consumption, using data from a sample of
      racially diverse, low-income adult clientele of five public health centers in Los
      Angeles County (n = 1503). We constructed a negative binomial regression model to
      examine the association between perceived food environment and the number of
      fruits and vegetables consumed. For every one point increase on the perceived
      food environment scale, individuals ate about 5% more fruits and vegetables (95%
      CI 1.007, 1.089), controlling for other covariates. Self-efficacy was shown to be
      a significant mediator (mediated effect = 0.010; 95% CI 0.002, 0.020), accounting
      for 22.9% of the effect. Efforts to increase access to healthy options may not
      only improve eating behaviors, but also influence individuals' beliefs that they
      can eat healthfully.

PMID- 25774039
TI  - Domestic Violence: Intersection of Culture, Gender and Context.
AB  - This study examines South Asian women's experience of domestic violence in Hong
      Kong. Despite the proliferation of literature on domestic violence, this issue
      remain unexplored in the discourse of domestic violence in Hong Kong. A
      qualitative research approach through face to face interview with 14 women was
      employed. Participants were recruited through purposive and snowball sampling.
      Findings from this study highlight the importance of considering the social and
      cultural influence on how women perceived and construct their experiences of
      abuse.Implications for practice and policies are highlighted. 

PMID- 25774040
TI  - Correlation of manganese with thyroid function in females having hypo- and
      hyperthyroid disorders.
AB  - The aim of present study was to compare the level of manganese (Mn) with thyroid
      functions, thyroid-stimulating hormone (TSH), free triiodothyronine (FT3), and
      free thyroxin (FT4) of females having hyper- (HPRT) and hypothyroid (HPOT)
      disorder. For comparative study, females of the same age group (16-30 years)
      having no thyroid disorders were selected as referents. The serum samples were
      acid digested prior to analysis by electrothermal atomic absorption spectrometry.
      The validity and accuracy of the methodology was checked by a certified sample.
      The resulted data indicated that the mean values of Mn in serum samples of
      females have hyperthyroidism was significantly higher than referent subjects (p <
      0.01), while lower values of Mn was observed in serum samples of hypothyroid
      patients. The mean values of FT3 and FT4 were found to be lower while TSH higher
      is in HPRT patients than age-matched healthy control females (p = <0.01). The
      reverse resulted data of these thyroid hormones was observed in HPOT patients
      (0.003).

PMID- 25774041
TI  - Oxidative Stress Markers and Histological Analysis in Diverse Organs from Rats
      Treated with a Hepatotoxic Dose of Cr(VI): Effect of Curcumin.
AB  - Hexavalent chromium [Cr(VI)] compounds are extremely toxic and carcinogenic.
      Despite the vast quantity of reports about Cr(VI) toxicity, the information
      regarding its effects when it is intraperitoneally (i.p.) administered is still
      limited. In contrast, it has been shown that curcumin prevents hepatotoxicity
      induced by a single intraperitoneal injection of 15 mg/kg body weight (b.w.) of
      potassium dichromate (K2Cr2O7). This study aims to evaluate oxidative stress
      markers, the activity of antioxidant enzymes, and the potential histological
      injury in brain, heart, lung, kidney, spleen, pancreas, stomach, and intestine
      from rats treated with a hepatotoxic dose of K2Cr2O7 (15 mg/kg b.w.), and the
      effect of curcumin pretreatment. Rats were divided into four groups: control,
      curcumin, K2Cr2O7, and curcumin+K2Cr2O7. At the end of the treatment, plasma and
      ascites fluid were collected and target organs were dissected out for biochemical
      and histological analysis. K2Cr2O7 induced hepatotoxicity but failed to induce in
      all the other studied organs either oxidative or histological injury, since
      levels of malondialdehyde (MDA), glutathione (GSH), and the activity of
      superoxide dismutase (SOD), catalase (CAT), and related GSH enzymes were
      unchanged. As expected, curcumin was safe. Lack of K2Cr2O7-induced toxicity in
      those target organs could be due to the following: (1) route of administration,
      (2) absorption through the portal circulation, (3) lower dose than needed, (4)
      short time of exposure, or (5) repeated doses are required to produce damage.
      Thus, the intraperitoneal injection of 15 mg/kg of K2Cr2O7, that is able to
      induce hepatotoxicity, was unable to induce histological and oxidative damage in
      other target organs. 

PMID- 25774042
TI  - Direct Method for Determination of Al, Cd, Cu, and Pb in Beers In Situ Digested
      by GF AAS Using Permanent Modifiers.
AB  - The object of the present study was to development of safe, reliable fast, and
      efficient methodologies for the direct determination of Al, Pb, Cu, and Cd in non
      digested beer samples of widely consumed brand name beers sold in Brazil, using
      graphite furnace absorption spectrometry (GF AAS). Pyrolysis and atomization
      temperature curves of selected chemical modifiers (iridium, rhodium, ruthenium,
      zirconium, and non-modifier use) were used to stabilize each metal and
      sensitivity in a beer sample was diluted to 1:1 with 0.2 % v/v nitric acid after
      degasification. The best modifier for aluminum was permanent zirconium, with a
      characteristic mass of 4.2 pg (recommended is 10 pg), demonstrating a symmetrical
      peak with a corrected background using a deuterium arc lamp. For cadmium and
      copper, the best modifier was permanent ruthenium with characteristic masses of
      0.3 and 7 pg (recommended are 0.35 and 4 pg, respectively, for Cd and Cu),
      respectively. The best condition for lead was using a non-modifier, with a
      characteristic mass of 6.9 pg (recommended is 10 pg). The limits of detection and
      mean recoveries, done over three consecutive days for aluminum, copper, lead, and
      cadmium, were 1.9, 2.9, 0.8, and 0.6 pg and 105, 104, 101, and 102 %,
      respectively. From the observed results, we may conclude that some metals, such
      as Al, Cd, Cu, and Pb, can be determined easily with graphite furnace atomic
      absorption spectrometry without sample digestion using a dilute nitric acid
      solution. 

PMID- 25774043
TI  - Iron Supplementation Attenuates the Inflammatory Status of Anemic Piglets by
      Regulating Hepcidin.
AB  - Iron deficiency is common throughout the world and has been linked to immunity
      impairments. Using piglets to model human infants, we assessed the impact of
      systemic iron homeostasis on proinflammatory status. Artificially reared piglets
      were parenterally supplied with iron dextran by intramuscular administration at
      the age of 3 days. Relative to no iron supplementation (control), iron dextran
      treated (FeDex) piglets increased hematological parameters as well as iron levels
      in serum and tissues from days 21 to 49. High expression of hepcidin was observed
      in FeDex-treated piglets, which correlated with suppressed expression of
      ferroportin in duodenum. Lower levels of proinflammatory cytokine (IL-6, TNF
      alpha, IFN-gamma, and IL-1beta) transcripts were detected in ileum of FeDex
      treated piglets, which indicated that iron supplementation could attenuate the
      increase of inflammatory cytokines caused by iron deficiency. Histopathological
      analysis of liver and duodenum proved the less inflammatory responses after iron
      supplementation. Hepcidin was highly stimulated by FeDex supplementation and
      attenuated the inflammation of anemia, which implied that hepcidin might had
      antiinflammatory function and is a candidate regulator of the cross-talk between
      iron regulation and inflammation. 

PMID- 25774045
TI  - The Fluoride Content of Yerba Mate Depending on the Country of Origin and the
      Conditions of the Infusion.
AB  - There are many reports of the positive effect of yerba mate on the human body.
      Elemental composition analysis of yerba mate revealed the presence of many
      microelements and macroelements, but there is no literature data referencing the
      content and the effect of the method of preparing the yerba mate infusion on the
      amount of released fluoride and thus the amount of this element supplied to the
      human body. Therefore, in the traditional way (cold and hot), we prepared
      infusions of yerba mate from different countries and determined in samples
      content of fluoride using potentiometric method. Hot infusions resulted in
      statistically significant (p = 0.03) increases in the amount of fluoride released
      from the dried material to the water, compared to brewing with water at room
      temperature. The successive refills of hot water also resulted in a release of
      the same amount of fluoride, although smaller than the infusion with water at
      room temperature (at the third refill, it was statistically significantly smaller
      at p = 0.003). With an increase in the number of hot water refills, the amount of
      fluoride released from the sample portion significantly decreased. Similar
      results were recorded when analyzing samples depending on the country of origin.
      The amount of fluoride released into the water differed statistically
      significantly depending on the country of origin. The most fluoride was
      determined in the infusions of yerba mate from Argentina and the least in
      infusions from Paraguay.

PMID- 25774044
TI  - Altering Genomic Integrity: Heavy Metal Exposure Promotes Transposable Element
      Mediated Damage.
AB  - Maintenance of genomic integrity is critical for cellular homeostasis and
      survival. The active transposable elements (TEs) composed primarily of three
      mobile element lineages LINE-1, Alu, and SVA comprise approximately 30% of the
      mass of the human genome. For the past 2 decades, studies have shown that TEs
      significantly contribute to genetic instability and that TE-caused damages are
      associated with genetic diseases and cancer. Different environmental exposures,
      including several heavy metals, influence how TEs interact with its host genome
      increasing their negative impact. This mini-review provides some basic knowledge
      on TEs, their contribution to disease, and an overview of the current knowledge
      on how heavy metals influence TE-mediated damage.

PMID- 25774046
TI  - Acute and chronic temperature effects on cardiovascular regulation in the red
      eared slider (Trachemys scripta).
AB  - Acute and chronic changes in ambient temperature alter several aspects of
      reptilian physiology. We investigated the effects of each type of temperature
      change on reptilian cardiovascular regulation in red-eared slider turtles
      (Trachemys scripta), a species known to experience marked seasonal changes in
      ambient temperature. Turtles were instrumented with occlusive catheters in the
      femoral artery and vein. Following an acclimation period of 10 days at 13 
      degrees C (13(1)), cardiovascular responses to adrenaline, and the cardiac limb
      of the baroreflex were quantified. Ambient temperature was then reduced 1 
      degrees C day(-1) until 3  degrees C was reached (3(1)). Turtles were maintained
      at this temperature for 1-week before cardiovascular responses were reassessed.
      Turtles were then gradually (1  degrees C day(-1)) returned to an ambient
      temperature of 13  degrees C, (13(2)). After a 1-week re-acclimation period,
      cardiovascular responses were again determined. Finally, 1-week post
      pharmacological manipulation of turtles in the 13(2) treatment, ambient
      temperature was reduced to 3  degrees C over 24 h (3(2)), and cardiovascular
      responses were again assessed. Temperature reduction from 13(1) to 3(1) decreased
      mean arterial blood pressure (P(m)) and heart rate (f(H)) by ~38 and ~63%,
      respectively. Acute temperature reduction, from 13(2) to 3(2), decreased f(H)
      similarly, ~66%; however, while P(m) decreased ~28%, this was not significantly
      different than P(m) at 13(2). The adrenaline injections increased f(H) ranging
      from 90 to 170% at 13  degrees C which was a greater change than that observed at
      3  degrees C ranging from a 40 to 70% increase. The increase in P m at the lowest
      dose of adrenaline did not differ across the temperature treatment groups. The
      operational point (set-point) P(m) of the baroreflex was decreased similarly by
      both methods of temperature reduction (3(1) or 3(2)). Further, a hypertensive
      cardiac baroreflex was absent in the majority of the animals studied independent
      of temperature. Baroreflex gain and normalized gain based on individual estimates
      of the relationship were decreased by temperature reduction similarly.
      Collectively, the data suggest that red-eared slider turtles modulate (down
      regulate) some cardiovascular control mechanisms during reduced ambient
      temperature.

PMID- 25774047
TI  - Timing matters: corticosterone injections 4 h before ovulation bias sex ratios
      towards females in chickens.
AB  - Birds have the ability to influence offspring sex prior to egg laying and may use
      hormones to mediate these skews. Corticosterone is of particular interest as a
      mediator of offspring sex because, as the primary stress hormone in birds, it
      regulates responses to environmental and social stimuli that trigger sex ratio
      biases. In previous studies in birds, chronic elevations of corticosterone
      stimulated female-biased sex ratios while acute pharmacological elevations that
      were provided 5 h prior to the expected time of ovulation stimulated male-biased
      sex ratios. Here, we aimed to determine the magnitude of corticosterone necessary
      to influence offspring sex and to further pinpoint the timing of the hormonal
      influence. Because high-dose injections of corticosterone stimulated male-biased
      sex ratios in hens, we hypothesized that females receiving acute pharmacological
      elevations of corticosterone would produce more male offspring while females with
      acute physiological elevations would produce an intermediate proportion of males
      compared to controls. We tested our hypotheses in laying hens by elevating
      corticosterone in the physiological or pharmacological range through injections
      of corticosterone administered 4 or 5 h prior to the expected time of ovulation.
      Contrary to our hypothesis, a physiological dose of corticosterone provided 5 h
      prior to the expected time of ovulation did not bias offspring sex ratios when
      compared to controls. Further, when corticosterone injections were given at 4 h
      prior to the expected time of ovulation, sex ratios were instead biased towards
      females. These results suggest that the timing and magnitude of the
      corticosterone elevation are both critical not only to whether a sex ratio bias
      occurs, but also the direction of the bias.

PMID- 25774048
TI  - What's trending in the infection prevention and control literature? From HIS 2012
      to HIS 2014, and beyond.
AB  - This is an informal review of some of the trends in the infection prevention and
      control literature since the last Healthcare Infection Society (HIS) conference
      in late 2012. Google Trends was used to investigate how the volume of interest in
      various infection control topics had changed over time. Ebola trumped all the
      others in Google searches, reflecting a surge of publications in the literature.
      Aside from Ebola, other trends in the infection prevention and control literature
      covered in this article include Middle East Respiratory Syndrome (MERS)
      coronavirus, universal versus targeted interventions, faecal microbiota
      transplantation, whole genome sequencing, carbapenem-resistant
      Enterobacteriaceae, and some aspects of environmental science. The review ends
      with an attempt to predict some of the trends in the infection prevention and
      control literature between now and the next HIS conference in 2016. 

PMID- 25774049
TI  - Incidence of delirium following total joint replacement in older adults: a meta
      analysis.
AB  - OBJECTIVE: Delirium is common in older adults following total joint replacement
      (TJR) of the hip and knee. However, reports of the incidence of delirium vary
      widely, limiting their usefulness. The current meta-analysis therefore examined
      (1) the incidence of delirium in older patients who underwent TJR and (2) whether
      these rates vary according to the (a) joint (hip/knee replacement), (b)
      inclusion/exclusion of patients who underwent simultaneous bilateral surgery, (c)
      inclusion/exclusion of patients with preexisting cognitive impairments, (d) type
      of anesthesia (regional/general), (e) method/frequency of assessment, and (f)
      postoperative interval. METHOD: Data from 24 studies (2,895 patients) that
      measured postsurgical delirium following TJR were analyzed. Mean weighted
      proportions were calculated using a random-effects model to assess the overall
      incidence of delirium and whether the rate varied according to the aforementioned
      variables. RESULTS: Overall, 17% of patients who underwent TJR developed delirium
      during hospital admission. Individual estimates varied from 0% to 82%, but this
      variability was not adequately explained by the variables that were examined.
      CONCLUSIONS: Delirium is relatively common following TJR; however, it remains
      unclear why individual estimates vary so widely. Health professionals working
      with these patients should remain alert to the presentation, diagnosis and
      management of delirium to optimize postsurgical outcomes.

PMID- 25774050
TI  - Pernicious anemia presenting as catatonia: correlating vitamin B12 levels and
      catatonic symptoms.
AB  - Pernicious anemia has been associated with various psychiatric manifestations,
      such as depression, mania and psychosis. Psychiatric symptoms can sometimes occur
      without hematological and neurological abnormalities and can be prodromal of
      vitamin B12 deficiency. We report a case of autoimmune B12 deficiency presenting
      as catatonia without signs of anemia or macrocytosis, in which a correlation was
      found between the patient's B12 blood levels and catatonic symptoms over time.
      This catatonic episode was successfully treated with only lorazepam and adequate
      doses of cyanocobalamin. 

PMID- 25774052
TI  - ERM proteins in cancer progression.

PMID- 25774053
TI  - How can biochemical reactions within cells differ from those in test tubes?

PMID- 25774051
TI  - Membrane curvature at a glance.
AB  - Membrane curvature is an important parameter in defining the morphology of cells,
      organelles and local membrane subdomains. Transport intermediates have simpler
      shapes, being either spheres or tubules. The generation and maintenance of
      curvature is of central importance for maintaining trafficking and cellular
      functions. It is possible that local shapes in complex membranes could help to
      define local subregions. In this Cell Science at a Glance article and
      accompanying poster, we summarize how generating, sensing and maintaining high
      local membrane curvature is an active process that is mediated and controlled by
      specialized proteins using general mechanisms: (i) changes in lipid composition
      and asymmetry, (ii) partitioning of shaped transmembrane domains of integral
      membrane proteins or protein or domain crowding, (iii) reversible insertion of
      hydrophobic protein motifs, (iv) nanoscopic scaffolding by oligomerized
      hydrophilic protein domains and, finally, (v) macroscopic scaffolding by the
      cytoskeleton with forces generated by polymerization and by molecular motors. We
      also summarize some of the discoveries about the functions of membrane curvature,
      where in addition to providing cell or organelle shape, local curvature can
      affect processes like membrane scission and fusion as well as protein
      concentration and enzyme activation on membranes. 

PMID- 25774055
TI  - Corrigendum.

PMID- 25774054
TI  - Child Maltreatment and the Adolescent Patient With Severe Obesity: Implications
      for Clinical Care.
AB  - OBJECTIVE: To characterize prevalence and correlates of child maltreatment (CM)
      in a clinical sample of adolescents with severe obesity. METHOD: Multicenter
      baseline data from 139 adolescents undergoing weight loss surgery (Mage = 16.9;
      79.9% female, 66.2% White; Mbody mass index [BMI] = 51.5 kg/m(2)) and 83
      nonsurgical comparisons (Mage = 16.1; 81.9% female, 54.2% White; MBMI = 46.9
      kg/m(2)) documented self-reported CM (Childhood Trauma Questionnaire) and
      associations with psychopathology, quality of life, self-esteem and body image,
      high-risk behaviors, and family dysfunction.  RESULTS: CM prevalence (females:
      29%; males: 12%) was similar to national adolescent base rates. Emotional abuse
      was most prevalent. One in 10 females reported sexual abuse. For females, CM
      rates were higher in comparisons, yet correlates were similar for both cohorts:
      greater psychopathology, substance use, and family dysfunction, and lower quality
      of life. CONCLUSION: While a minority of adolescents with severe obesity reported
      a CM history, they carry greater psychosocial burden into the clinical setting.

PMID- 25774056
TI  - A qualitative study of the impact of the UK 'bedroom tax'.
AB  - BACKGROUND: The implementation of the 'Removal of the Spare Room Subsidy' in
      April 2013, commonly known as the 'bedroom tax', affects an estimated 660 000
      working age social housing tenants in the UK, reducing weekly incomes by L12-L22.
      This study aimed to examine the impact of this tax on health and wellbeing in a
      North East England community in which 68.5% of residents live in social housing.
      METHODS: Qualitative study using interviews and a focus group with 38 social
      housing tenants and 12 service providers. RESULTS: Income reduction affected
      purchasing power for essentials, particularly food and utilities. Participants
      recounted negative impacts on mental health, family relationships and community
      networks. The hardship and debt that people experienced adversely affected their
      social relationships and ability to carry out normal social roles. Residents and
      service providers highlighted negative impacts on the neighbourhood, as well as
      added pressure on already strained local services. CONCLUSIONS: The bedroom tax
      has increased poverty and had broad-ranging adverse effects on health, wellbeing
      and social relationships within this community. These findings strengthen the
      arguments for revoking this tax.

PMID- 25774057
TI  - Takayasu arteritis in southern Sweden.
AB  - OBJECTIVE: To study the epidemiology and clinical characteristics of Takayasu
      arteritis (TA) in southern Sweden. METHODS: The study area is situated in Skane,
      the southernmost county in Sweden (total population December 2011: 983,419, 50.5%
      women). Patients were identified using clinical registries in all the 5 hospitals
      and private rheumatology clinics within the study area between the years 1997 and
      2011. The diagnosis of TA was confirmed by medical records review. Only patients
      fulfilling the 1990 American College of Rheumatology classification criteria were
      included. RESULTS: Thirteen patients (all women) were identified. The median age
      at diagnosis was 23 years [interquartile range (IQR) 16-38]. Ten patients were
      diagnosed between 1997 and 2011. The annual incidence rate was estimated to
      0.7/million inhabitants (95% CI 0.3-1.2) and 1.5/million among women (95% CI 0.6
      2.4). Patients were followed for a median of 9 years (IQR 4-17.5). As of January
      1, 2012, all 13 patients were alive and living within the study area. The point
      prevalence per million inhabitants was 13.2 (95% CI 6.0-20.4), and 26.2 among
      women (95% CI 11.9-40.4). Subclavian arteries were the most commonly affected
      vessels. Organ damage was common, affecting all patients. Seven pregnancies
      resulting in 5 live births and 2 abortions were registered after the diagnosis of
      TA. CONCLUSION: The incidence of TA in Sweden is comparable to recently reported
      rates from other European studies, while the prevalence is higher than previously
      reported. The prognosis of TA is good, but the rate of damage is high.

PMID- 25774058
TI  - Prednisone in Uric Acid Lowering in Symptomatic Heart Failure Patients with
      Hyperuricemia -- The PUSH-PATH3 Study.
AB  - OBJECTIVE: To determine the safety and efficacy of prednisone in patients with
      symptomatic heart failure (HF) and hyperuricemia. METHODS: Prednisone therapy was
      administered for a short time to 191 symptomatic HF patients with hyperuricemia
      (serum uric acid > 7 mg/dl). RESULTS: Prednisone significantly reduced serum uric
      acid by 2.99 mg/dl (p < 0.01) and serum creatinine by 0.17 mg/dl (p < 0.01).
      These favorable effects were associated with a remarkable increase in urine
      output, improvement in renal function, and improvement in clinical status.
      CONCLUSION: Prednisone can be used safely in symptomatic HF patients with
      hyperuricemia.

PMID- 25774059
TI  - The OMERACT Ultrasound Working Group 10 Years On: Update at OMERACT 12.
AB  - Musculoskeletal ultrasound (US) now thrives as an established imaging modality
      for the investigation and management of chronic inflammatory arthritis. We
      summarize here results of the Outcome Measures in Rheumatology (OMERACT) US
      working group (WG) projects of the last 2 years. These results were reported at
      the OMERACT 12 meeting at the plenary session and discussed during breakout
      sessions. Topics included standardization of US use in rheumatic disease over the
      last decade and its contribution to understanding musculoskeletal diseases. This
      is the first update report of WG activities in validating US as an outcome
      measure in musculoskeletal inflammatory and degenerative diseases, including
      pediatric arthritis, since the OMERACT 11 meeting. 

PMID- 25774060
TI  - Effect of Smoking on Remission Proportions Differs Between Male and Female
      Patients with Rheumatoid Arthritis: A Study Based on the IORRA Survey.
AB  - OBJECTIVE: To analyze sex difference in the effect of smoking on remission
      proportions in patients with rheumatoid arthritis (RA). METHODS: Subjects were
      Japanese patients with RA who participated in the IORRA survey conducted in April
      2011 and reported smoking status. Clinical characteristics, treatment status, and
      the percentages achieving remission were compared between subjects stratified by
      sex and smoking status. To confirm the differential effects of sex and smoking
      status on remission, we used multivariate logistic regression models with the
      dependent variable as 28-joint Disease Activity Score (DAS28) remission. RESULTS:
      Among 810 men and 4206 women, 162 (20.0%) and 3173 (75.4%), respectively, were
      never smokers; 208 (25.7%) and 314 (7.5%), respectively, were current smokers. In
      men, never smokers tended to have higher remission proportions than past and
      current smokers. In contrast, smoking status seemed not to affect remission in
      women. Except for lower corticosteroid dose in male never smokers, no significant
      differences were observed in comparing treatment status. By multivariate
      analyses, male past and current smokers were negatively associated with DAS28
      erythrocyte sedimentation rate remission compared to male never smokers [OR 0.66
      and 0.61, 95% CI (0.44-0.98) and (0.39-0.96), respectively]. However, female past
      and current smokers were not associated with remission compared to female never
      smokers [OR 1.04 and 1.19, 95% CI (0.86-1.25) and (0.91-1.54), respectively].
      CONCLUSION: We demonstrated that the effect of smoking on remission proportions
      differed between men and women. Our findings suggest that both sex and smoking
      status are important considerations when planning a treatment strategy for
      patients with RA.

PMID- 25774061
TI  - Tenascin-C Levels, A Toll-like Receptor 4 Ligand, in Enthesitis-related Arthritis
      Category of Juvenile Idiopathic Arthritis: A Cross-sectional and Longitudinal
      Study.
AB  - OBJECTIVE: Monocytes of children with enthesitis-related arthritis (ERA) show
      Toll-like receptor 4 (TLR4) overexpression. Tenascin-C (TNC) is an extracellular
      matrix glycoprotein and acts as an endogenous TLR4 ligand. Thus, we studied the
      serum and synovial fluid (SF) levels of TNC in children with ERA. METHODS: TNC
      was measured in the serum of 80 children with ERA satisfying the International
      League of Associations for Rheumatology criteria. Fifteen children were followed
      up while being treated with regular nonsteroidal antiinflammatory drug (NSAID)
      therapy and levels were reassessed at 3 months. Seventeen paired serum-SF samples
      and 25 healthy control serum samples were also analyzed. Disease activity was
      assessed by physician's global assessment (PGA), early morning stiffness (EMS),
      tender (TJC) and swollen joint counts (SJC), enthesitis score, erythrocyte
      sedimentation rate (ESR), and C-reactive protein (CRP). RESULTS: The mean serum
      TNC level in patients with active disease (67.1 +/- 44.9 ng/ml) was significantly
      higher than in those with inactive disease (40.6 +/- 36.7 ng/ml, p = 0.01) and
      healthy controls (21 +/- 15.2 ng/ml, p < 0.001). Levels of TNC were higher in HLA
      B27-positive (58.4 ng/ml) versus -negative disease (20.4 ng/ml, p = 0.01). TNC
      levels correlated moderately with disease activity: PGA r = 0.4, EMS r = 0.34,
      TJC r = 0.4, SJC r = 0.46, ESR r = 0.42, and CRP r = 0.32. In receiver-operation
      characteristic analysis for active versus inactive diseases, TNC [area under the
      curve (AUC) = 0.754] was equivalent to ESR (AUC = 0.787) and CRP (AUC = 0.789).
      Regular NSAID therapy led to a significant fall in serum TNC levels at 3 months
      (p = 0.0003). The SF TNC level was 17.39 ng/ml, significantly lower than the
      paired serum values (p = 0.01). CONCLUSION: Serum TNC levels are significantly
      raised and correlate with various clinical and laboratory variables of disease
      activity in children with ERA. Regular NSAID therapy reduces the TNC levels,
      probably related to controlling disease activity.

PMID- 25774062
TI  - Effectiveness of total contact insoles in patients with plantar fasciitis.
AB  - OBJECTIVE: To assess the effectiveness of total contact insoles (TCI) in patients
      with plantar fasciitis (PF). METHODS: A double-blind randomized controlled trial
      was carried out with intention-to-treat analysis. Seventy-four patients were
      randomly allocated to use a TCI made of ethylene vinyl acetate (study group, n =
      37) or a flat insole (control group, n = 37). The following assessment tools were
      used: visual analog scale for pain while walking and at rest, Medical Outcomes
      Study Short Form-36 (SF-36) for quality of life, Foot Function Index and Foot
      Health Status Questionnaire for foot function, 6-min walk test (6MWT), and
      baropodometer FootWalk Pro for plantar pressure analysis. The groups were
      evaluated by a blinded assessor at baseline and after 45, 90, and 180 days.
      RESULTS: The groups were homogeneous for the majority of variables at baseline.
      The over-time comparisons show a statistical difference between the groups for
      pain while walking (p = 0.008) and the 6MWT (p = 0.010). Both groups showed
      significant improvements in pain at rest, foot function, and some quality of life
      variables (physical functioning, bodily pain, vitality, and social functioning),
      with no significant statistical differences between them. The baropodometer
      recorded no changes from the use of the insoles. CONCLUSION: A TCI can be used to
      reduce pain while walking and to increase walking distance in individuals with
      PF.

PMID- 25774063
TI  - Optimization of the Energy Window for PETbox4, a Preclinical PET Tomograph With a
      Small Inner Diameter.
AB  - Small animal positron emission tomography (PET) systems are often designed by
      employing close geometry configurations. Due to the different characteristics
      caused by geometrical factors, these tomographs require data acquisition
      protocols that differ from those optimized for conventional large diameter ring
      systems. In this work we optimized the energy window for data acquisitions with
      PETbox4, a 50 mm detector separation (box-like geometry) pre-clinical PET
      scanner, using the Geant4 Application for Tomographic Emission (GATE). The
      fractions of different types of events were estimated using a voxelized phantom
      including a mouse as well as its supporting chamber, mimicking a realistic mouse
      imaging environment. Separate code was developed to extract additional
      information about the gamma interactions for more accurate event type
      classification. Three types of detector backscatter events were identified in
      addition to the trues, phantom scatters and randoms. The energy window was
      optimized based on the noise equivalent count rate (NECR) and scatter fraction
      (SF) with lower-level discriminators (LLD) corresponding to energies from 150 keV
      to 450 keV. The results were validated based on the calculated image uniformity,
      spillover ratio (SOR) and recovery coefficient (RC) from physical measurements
      using the National Electrical Manufacturers Association (NEMA) NU-4 image quality
      phantom. These results indicate that when PETbox4 is operated with a more narrow
      energy window (350-650 keV), detector backscatter rejection is unnecessary. For
      the NEMA NU-4 image quality phantom, the SOR for the water chamber decreases by
      about 45% from 15.1% to 8.3%, and the SOR for the air chamber decreases by 31%
      from 12.0% to 8.3% at the LLDs of 150 and 350 keV, without obvious change in
      uniformity, further supporting the simulation based optimization. The
      optimization described in this work is not limited to PETbox4, but also
      applicable or helpful to other small inner diameter geometry scanners.

PMID- 25774064
TI  - Nickel-Catalyzed Suzuki-Miyaura Cross-Coupling in a Green Alcohol Solvent for an
      Undergraduate Organic Chemistry Laboratory.
AB  - A modern undergraduate organic chemistry laboratory experiment involving the
      Suzuki-Miyaura coupling is reported. Although Suzuki-Miyaura couplings typically
      employ palladium catalysts in environmentally harmful solvents, this experiment
      features the use of inexpensive nickel catalysis, in addition to a "green"
      alcohol solvent. The experiment employs heterocyclic substrates, which are
      important pharmaceutical building blocks. Thus, this laboratory procedure exposes
      students to a variety of contemporary topics in organic chemistry, including
      transition metal-catalyzed cross-couplings, green chemistry, and the importance
      of heterocycles in drug discovery, none of which are well represented in typical
      undergraduate organic chemistry curricula. The experimental protocol uses
      commercially available reagents and is useful in both organic and inorganic
      instructional laboratories.

PMID- 25774065
TI  - Using Neural Data to Test A Theory of Investor Behavior: An Application to
      Realization Utility.
AB  - We use measures of neural activity provided by functional magnetic resonance
      imaging (fMRI) to test the "realization utility" theory of investor behavior,
      which posits that people derive utility directly from the act of realizing gains
      and losses. Subjects traded stocks in an experimental market while we measured
      their brain activity. We find that all subjects exhibit a strong disposition
      effect in their trading, even though it is suboptimal. Consistent with the
      realization utility explanation for this behavior, we find that activity in the
      ventromedial prefrontal cortex, an area known to encode the value of options
      during choices, correlates with the capital gains of potential trades; that the
      neural measures of realization utility correlate across subjects with their
      individual tendency to exhibit a disposition effect; and that activity in the
      ventral striatum, an area known to encode information about changes in the
      present value of experienced utility, exhibits a positive response when subjects
      realize capital gains. These results provide support for the realization utility
      model and, more generally, demonstrate how neural data can be helpful in testing
      models of investor behavior.

PMID- 25774066
TI  - Family Ties and Young Fathers' Engagement in Cape Town, South Africa.
AB  - Young South African fathers are often engaged in their children's lives even if
      they do not live together. Using longitudinal data on children (n = 1,209) from
      the Cape Town area, the authors show that although only 26% of young fathers live
      with their children, 66% of nonresidential fathers maintain regular contact, and
      61% provide financial support. The father-child relationship, however, is
      embedded in broader family ties. The type of father-mother relationship is
      strongly associated with whether fathers coreside with their children, but not
      with fathers' contact with nonresidential children. Close mother and maternal
      grandmother bonds reduce the likelihood that fathers live with their children,
      whereas close ties between fathers and paternal grandmothers increase the chance
      that fathers visit nonresidential children. Family ties do not affect fathers'
      financial contributions, which are driven by men's current economic situation.
      These findings illustrate that father-child relationships are best understood in
      the context of interacting family systems.

PMID- 25774067
TI  - Expecting motherhood? Stratifying reproduction in twenty-first century Scottish
      abortion practice.
AB  - This article illustrates how Scottish health professionals involved in
      contemporary abortion provision construct stratified expectations about women's
      reproductive decision-making. Drawing on 42 semi-structured interviews I reveal
      the contingent discourses through which health professionals constitute the
      'rationality' of the female subject who requests abortion. Specifically, I
      illustrate how youth, age, parity and class are mobilised as criteria through
      which to distinguish 'types' of patient whose requests for abortion are deemed
      particularly understandable or particularly problematic. I conceptualise this
      process of differentiation as a form of 'stratified reproduction' (Colen, 1995;
      Ginsburg and Rapp, 1995) and argue that it is significant for two reasons.
      Firstly, it illustrates the operation of dominant discourses concerning abortion
      and motherhood in twenty-first century Britain. Secondly, it extends the forms of
      critique which feminist scholarship has, to date, developed of the regulation of
      abortion provision in the UK.

PMID- 25774068
TI  - The Effect of Group Logotherapy on Meaning in Life and Depression Levels of
      Iranian Students.
AB  - This paper identifies the effectiveness of group logotherapy in reducing
      depression and increasing meaning in life levels of university students in Iran.
      A randomized controlled trial was conducted with a pre- post- and follow-up test
      design. The instruments used were the Purpose in Life (PIL) test and the Beck
      Depression Inventory (BDI). Data were collected from 10 subjects in an
      experimental group and 10 in a control group. The experimental group participated
      in 10 sessions of group logotherapy, whilst the control group received no
      intervention. The mean scores for depression levels was significantly lower in
      the experimental group than in the control group and significantly higher in
      regard to meaning in life. Results suggest that group logotherapy has the
      potential to reduce depression levels and improve the meaning in life of
      university students.

PMID- 25774069
TI  - Debiasing the disposition effect by reducing the saliency of information about a
      stock's purchase price.
AB  - The disposition effect refers to the empirical fact that investors have a higher
      propensity to sell risky assets with capital gains compared to risky assets with
      capital losses, and it has been associated with low trading performance. We use a
      stock trading laboratory experiment to investigate if it is possible to reduce
      subjects' tendency to exhibit a disposition effect by making information about a
      stock's purchase price, and thus about capital gains and losses, less salient. We
      compare two experimental conditions: a high-saliency condition in which the
      purchase price of a stock is prominently displayed by the trading software, and a
      low-saliency condition in which it is not displayed at all. We find that
      individuals exhibit a disposition effect in the high-saliency condition, and that
      the effect is 25% smaller in the low-saliency condition. This suggests that it is
      possible to debias the disposition effect by reducing the saliency with which
      information about a stock's purchase price is displayed on financial statements
      and online trading platforms.

PMID- 25774070
TI  - INTEGRATING TECHNOLOGICAL ADVANCEMENTS IN BEHAVIORAL INTERVENTIONS TO PROMOTE
      HEALTH: UNPRECEDENTED OPORTUNITIES FOR BEHAVIOR ANALYSTS.
AB  - The use of mobile devices is growing worldwide in both industrialized and
      developing nations. Alongside the worldwide penetration of web-enabled devices,
      the leading causes of morbidity and mortality are increasingly modifiable
      lifestyle factors (e.g., improving one's diet and exercising more). Behavior
      analysts have the opportunity to promote health by combining effective behavioral
      methods with technological advancements. The objectives of this paper are (1) to
      highlight the public health gains that may be achieved by integrating technology
      with a behavior analytic approach to developing interventions, and (2) to review
      some of the currently, under-examined issues related to merging technology and
      behavior analysis (enhancing sustainability, obtaining frequent measures of
      behavior, conducting component analyses, evaluating cost-effectiveness,
      incorporating behavior analysis in the creation of consumer-based applications,
      and reducing health disparities). Thorough consideration of these issues may
      inspire the development, implementation, and dissemination of innovative,
      efficacious interventions that substantially improve global public health.

PMID- 25774071
TI  - Protective factors in the development of early child conduct problems.
AB  - The present study utilized a resilience model to investigate child, family, and
      community protective factors in toddlerhood as they relate to low levels of
      conduct problems at age 5 in a sample of low income children at risk for early
      disruptive problem behavior. Child, family, and community factors were associated
      with lower levels of conduct problems at age 5. Child, family, and community
      protective factors also distinguished between children who remained below and
      above a clinical threshold for aggressive problems between age 2 and 5. Finally,
      each domain of protective factors made small but significant unique contributions
      to lower aggression at age 5. These results emphasize the importance of
      multivariate analysis of the ecology of development predicting child outcome, and
      suggest potential areas for intervention with children at high risk for conduct
      problems.

PMID- 25774072
TI  - An Existential-Humanistic View of Personality Change: Co-Occurring Changes with
      Psychological Well-Being in a 10 Year Cohort Study.
AB  - Increasingly, psychological research has indicated that an individual's
      personality changes across the lifespan. We aim to better understand personality
      change by examining if personality change is linked to striving towards
      fulfilment, as suggested by existential-humanistic theories of personality
      dynamics. Using the Wisconsin Longitudinal Study, a cohort of 4,733 mid-life
      individuals across 10 years, we show that personality change was significantly
      associated with change in existential well-being, represented by psychological
      well-being (PWB). Moreover, personality change was more strongly related to
      change in PWB than changes in other well-being indicators such as depression,
      hostility and life satisfaction. Personality changed to a similar degree and
      explained greater variation in our well-being measures than changes in
      socioeconomic variables. The findings indicate personality change is necessary
      for the holistic development of an individual, supporting a greater need to
      understand personality change and increasing room for use of personality measures
      as indicators of well-being and policy making.

PMID- 25774073
TI  - Optimization on the space of rigid and flexible motions: an alternative manifold
      optimization approach.
AB  - In this paper we consider the problem of minimization of a cost function that
      depends on the location and poses of one or more rigid bodies, or bodies that
      consist of rigid parts hinged together. We present a unified setting for
      formulating this problem as an optimization on an appropriately defined manifold
      for which efficient manifold optimizations can be developed. This setting is
      based on a Lie group representation of the rigid movements of a body that is
      different from what is commonly used for this purpose. We illustrate this
      approach by using the steepest descent algorithm on the manifold of the search
      space and specify conditions for its convergence.

PMID- 25774074
TI  - Benzoquinones from scent glands of phalangiid harvestmen (Arachnida, Opiliones,
      Eupnoi): a lesson from Rilaena triangularis.
AB  - In case of disturbance, the phalangiine harvestman Rilaena triangularis (Eupnoi,
      Phalangiidae) emits a directed jet from large prosomal scent ("defensive")
      glands. The pungent-smelling secretion was analyzed by gas chromatography-mass
      spectrometry and found to contain mainly 1,4-benzoquinone along with 1,4
      naphthoquinone and caprylic (=octanoic) acid. While various alkylated
      benzoquinones are characteristic for the scent gland secretions of many
      grassatorean Laniatores, this is the first incidence of benzoquinone-based
      chemical defense in palpatorean harvestmen.

PMID- 25774075
TI  - Iterative deconvolution technique for measurements of diffraction-limited images
      on optical microscopes.
AB  - Diffraction limit is usually a thorny problem in an optical inspection system. In
      this investigation, a model-based deconvolution technique was developed to
      recover diffraction-limited images, where images with sizes smaller than the
      diffraction limit could be recognized. Experiments were carried out with a
      traditional microscope at 200* magnification coupled with a halogen light source
      for a series of line width samples. The point spread function of the imaging
      optics was first obtained from an estimated model and then combined with a
      nonlinear deconvolution algorithm to calculate the full width at half maximum and
      reconstruct the line widths. Experimental results indicate that a measurement
      error below one pixel size of the measurement system is achievable. Accordingly,
      the target of nanoscale line width inspection based on a low cost and real-time
      image processing technique can be fulfilled, which greatly increases the ability
      of nanoscaling on optical microscopes.

PMID- 25774077
TI  - A simplified Katsevich algorithm motivated by the distribution properties of k
      lines.
AB  - The Katsevich algorithm is a breakthrough in the theoretically exact algorithms
      for helical cone beam CT. For future application in medical and industrial CT,
      determining how to implement it efficiently and accurately is the main task. We
      analyzed the slope law and intersection law of the k-lines, finding that the k
      lines are not intersecting if the half maximal fan angle (HMFA) is less than 21
      degrees  (numerical solution, so it is approximate) and that the helical pitch
      and HMFA determine the depth of parallelism of k-lines. Using an appropriate
      pitch and a HWFA that is less than 21 degrees , one can use a simplified
      Katsevich algorithm, whose filtration process can be done on the rows of the
      detector panel so that the pre-weighting, pre-rebinning, post-rebinning and post
      weighting steps are all canceled. Simulation experiments show that the simplified
      algorithm can obtain highly precise images at a faster speed. Our results are
      intended to be valuable to those who are working on efficient implementations of
      the Katsevich-type algorithms.

PMID- 25774076
TI  - Ion binding to biological macromolecules.
AB  - Biological macromolecules carry out their functions in water and in the presence
      of ions. The ions can bind to the macromolecules either specifically or non
      specifically, or can simply to be a part of the water phase providing
      physiological gradient across various membranes. This review outlines the
      differences between specific and non-specific ion binding in terms of the
      function and stability of the corresponding macromolecules. Furthermore, the
      experimental techniques to identify ion positions and computational methods to
      predict ion binding are reviewed and their advantages compared. It is indicated
      that specifically bound ions are relatively easier to be revealed while non
      specifically associated ions are difficult to predict. In addition, the binding
      and the residential time of non-specifically bound ions are very much sensitive
      to the environmental factors in the cells, specifically to the local pH and ion
      concentration. Since these characteristics differ among the cellular
      compartments, the non-specific ion binding must be investigated with respect to
      the sub-cellular localization of the corresponding macromolecule.

PMID- 25774078
TI  - Ankle-Foot Orthoses: Proprioceptive Inputs and Balance Implications.
AB  - Individuals with a loss of sensation in the lower limbs frequently experience
      postural instability, altered gait patterns, and an increased risk of falling
      culminating in a decreased quality of life. Previous studies have documented that
      using ankle-foot orthoses (AFOs) help such individuals to maintain their balance.
      This study was conducted to investigate whether somatosensory cues delivered to
      the intact tissues of the lower limbs above the ankle joints enhance the control
      of posture in individuals with peripheral neuropathy. The study involved 12
      individuals with sensory neuropathy because of diabetes who participated in
      static and dynamic balance tests with and without specially designed AFOs that
      provided auxiliary sensory cues to the lower limbs without stabilizing the ankle
      joints. During the tests, the subjects were required to alternately stand on a
      fixed and moving platform with their eyes alternately open or closed. Equilibrium
      scores and response latencies were obtained. The results showed that equilibrium
      scores were significantly higher in experiments with the specially modified AFOs
      compared with conditions without AFOs. Smaller latency scores were recorded in
      conditions with AFOs as well. The outcome indicates that AFOs that substitute for
      the lack of proprioceptive feedback may improve automatic postural responses in
      individuals with diabetic peripheral neuropathy. It also highlights the need for
      further research focused on the design of assistive means that could improve the
      balance and the performance of activities of daily living in individuals with
      proprioceptive deficits.

PMID- 25774079
TI  - Perceived Social Support and Mental Health Among Single vs. Partnered Polish
      Young Adults.
AB  - The aim of this study was to examine whether young adults in nonmarital romantic
      relationships experience better mental health and lower levels of mental health
      problems compared to single young adults. In addition, the current study also
      tested the hypothesis that perceived social support mediates the association
      between relationship status (single vs. partnered) and mental health, and mental
      health problems. Five hundred fifty three participants (335 females and 218
      males) aged 20-30 completed the Polish versions of General Health Questionnaire
      28, Mental Health Continuum-Short Form, Social and Emotional Loneliness Scale for
      Adults-Short Form, and Multidimensional Scale of Perceived Social Support.
      Results indicated that single individuals reported lower emotional well-being
      than partnered individuals. No differences emerged between single and partnered
      individuals in regard to social and psychological well-being, as well in total
      well-being. Results also revealed no differences between single and partnered
      individuals in regard to somatic symptoms, anxiety and insomnia, social
      dysfunction, severe depression, and total mental health problems. Mediational
      analyses indicated the perceived social support mediates the association between
      partner status and mental health problems.

PMID- 25774080
TI  - Genome editing in plants via designed zinc finger nucleases.
AB  - The ability to create DNA double-strand breaks (DSBs) at specified genomic
      locations, which then stimulate the cell's naturally occurring DNA repair
      processes, has introduced intriguing possibilities for genetic modification. Zinc
      finger nucleases (ZFNs) are designed restriction enzymes consisting of a
      nonspecific cleavage domain fused to sequence-specific DNA binding domains. ZFN
      mediated DSB formation at endogenous genomic loci followed by error-prone non
      homologous end joining (NHEJ) repair can result in gene-specific mutations via
      nucleotide base pair insertions or deletions. Similarly, specific DNA sequence
      modifications can be made by providing donor DNA templates homologous to
      sequences flanking the cleavage site via homology-directed repair (HDR). Targeted
      deletions of intervening DNA sequence can be obtained by ZFNs used to create
      concurrent DSBs. Site-specific transgene integration into ZFN-induced DSBs is
      possible via either NHEJ or HDR. Genome editing can be used to enhance our basic
      understanding of plant gene function as well as modify and improve crop plants.
      As with conventional plant transformation technology, the efficiency of genome
      editing is absolutely dependent on the ability to initiate, maintain, and
      regenerate plant cell and tissue cultures.

PMID- 25774081
TI  - In vitro regeneration of eight cultivars of Brassica oleracea var. capitata.
AB  - Eight cultivars of Brassica oleracea var. capitata and two types of explant
      (hypocotyl and cotyledon) were tested for their potential to regenerate under in
      vitro conditions. Hypocotyl and cotyledon explants from 10-d-old seedlings were
      subcultured onto different callus induction media based on Murashige and Skoog
      (MS) basal medium supplemented with 1% sucrose and different concentrations and
      combinations of plant growth regulators. Hypocotyl explants were found to be more
      suitable for callus induction and organogenesis than cotyledon explants for all
      cultivars tested. In terms of regeneration, the cv. 'Amager' was significantly
      more responsive than the other cultivars tested and produced the highest number
      of shoots/buds per explant. Moreover, among five types of media tested, MS + 8.88
      MUM 6-benzyloaminopurine (BAP) + 0.53 MUM alpha-naphthylacetic acid (NAA) was
      most effective for shoot regeneration. Rooting was achieved within 10-15 d on all
      the rooting media, but MS medium containing 5.37 MUM NAA produced the maximum
      number of strong and healthy roots. Plantlets (95%) were subsequently established
      in the greenhouse, and no phenotypic variations were observed among regenerated
      plants. This plant regeneration protocol could be suitable for a wide range of
      cabbage cultivars.

PMID- 25774082
TI  - Development and Initial Evaluation of a Web-Based Program to Increase Parental
      Awareness and Monitoring of Underage Alcohol Use: A Brief Report.
AB  - The development of a web-based parent-focused intervention to improve parental
      awareness and monitoring of adolescent alcohol use was preliminarily evaluated.
      Upon completion of baseline assessment, sixty-seven parents were randomly
      assigned to the experimental web-based parent-focused intervention or an
      assessment only control condition. Participants who completed the experimental
      program, relative to control participants, significantly improved knowledge of
      problems related to underage drinking (p < .01) while improvements in overall
      monitoring of their children approached significance (p = .08). Improvements in
      monitoring by experimental participants, relative to controls, were pronounced in
      phone monitoring (p < .01) and indirect monitoring (p = .05). Participants in
      this study improved their communication about alcohol from pre- to post
      intervention regardless of intervention. There were no statistical between group
      differences found regarding underage drinking attitudes. This pilot evaluation
      demonstrates that this program warrants further examination in controlled trials
      with greater power. Study implications are discussed in light of results.

PMID- 25774083
TI  - Polarization Effects in Optical Coherence Tomography of Various Biological
      Tissues.
AB  - Polarization sensitive optical coherence tomography (PS-OCT) was used to obtain
      spatially resolved ex vivo images of polarization changes in skeletal muscle,
      bone, skin and brain. Through coherent detection of two orthogonal polarization
      states of the signal formed by interference of light reflected from the
      biological sample and a mirror in the reference arm of a Michelson
      interferometer, the depth resolved change in polarization was measured. Inasmuch
      as any fibrous structure will influence the polarization of light, PS-OCT is a
      potentially powerful technique investigating tissue structural properties. In
      addition, the effects of single polarization state detection on OCT image
      formation is demonstrated.

PMID- 25774084
TI  - A population based study on the prevalence of cigarette smoking and smokers'
      characteristics at osogbo, Nigeria.
AB  - BACKGROUND: Cigarette smoking has been linked to several cancers worldwide. The
      characteristics of smokers have not been well documented among Nigerians.
      OBJECTIVE: This study assessed the prevalence and characteristics of cigarette
      smokers among the residents of Osogbo, in southwestern Nigeria. METHOD: The
      study, a population based cross-sectional study of randomly selected consenting
      adult residents of Osogbo, was conducted in September of 2011. Data was collected
      using a semi-structured interviewer administered questionnaire on cigarette
      smoking. RESULTS: A total of 759 respondents were interviewed. Mean age was 42.1
      +/- 12.5 years. There were 364 (48%) males and 395 (52%) females. About 22% had
      ever smoked while 8.7% were current smokers, smoking an average of 22.9 +/- 10.1
      cigarettes per day. Males constituted the majority of current smokers. Most
      smokers (71%) were introduced to smoking by friends and ill health was the most
      often reported reason for quitting. CONCLUSION: Cigarette smoking is commonly
      practiced among males in the studied population and awareness creation and
      advocacy should be conducted throughout the city in order to inform current
      smokers about the hazards and cumulative effects inherent in smoking.

PMID- 25774085
TI  - Culturally tailored smoking cessation for arab american male smokers in community
      settings: a pilot study.
AB  - Tobacco use is a serious public health problem among Arab Americans with limited
      English proficiency. The main goal of this study was to develop a culturally
      tailored and linguistically-sensitive Arabic-language smoking cessation program.
      A secondary goal was to evaluate the feasibility of recruiting Arab Americans
      through a faith-based community organization which serves as a neighborhood
      social center for the city of Richmond's Arab Americans. Eight first-generation
      Arab American men aged 20 years and above completed the three-month program.
      There was general agreement of the following: (1) each stage of the five-stage
      cessation program could be improved; (2) several glaring errors could be easily
      corrected; and (3) minor variation among the various countries-of-origin of
      participants could lead to a few changes in the program with respect to the use
      of some colloquial terms. The results suggest that it is possible to reach
      smokers from Arab American communities with a tailored Arabic language smoking
      cessation program. The findings of this report will be used as the basis for a
      large-scale intervention study of a culturally and linguistically sensitive
      cessation program for Arab American ethnic groups. 

PMID- 25774086
TI  - Metabotropic glutamate receptor 5 shows different patterns of localization within
      the parallel visual pathways in macaque and squirrel monkeys.
AB  - Glutamate is used as an excitatory neurotransmitter by the koniocellular (K),
      magnocellular (M), and parvocellular (P) pathways to transfer signals from the
      primate lateral geniculate nucleus (LGN) to primary visual cortex (V1). Glutamate
      acts through both fast ionotropic receptors, which appear to carry the main
      sensory message, and slower, modulatory metabotropic receptors (mGluRs). In this
      study, we asked whether mGluR5 relates in distinct ways to the K, M, and P LGN
      axons in V1. To answer this question, we used light microscopic
      immunocytochemistry and preembedding electron microscopic immunogold labeling to
      determine the localization of mGluR5 within the layers of V1 in relation to the
      K, M, and P pathways in macaque and squirrel monkeys. These pathways were labeled
      separately via wheat germ agglutinin-horseradish peroxidase (WGA-HRP) injections
      targeting the LGN layers. mGluR5 is of interest because it: 1) has been shown to
      be expressed in the thalamic input layers; 2) appears to be responsible for some
      types of oscillatory firing, which could be important in the binding of visual
      features; and 3) has been associated with a number of sensory-motor gating
      related pathologies, including schizophrenia and autism. Our results demonstrated
      the presence of mGluR5 in the neuropil of all V1 layers. This protein was lowest
      in IVCalpha (M input) and the infragranular layers. In layer IVC, mGluR5 also was
      found postsynaptic to about 30% of labeled axons, but the distribution was
      uneven, such that postsynaptic mGluR5 label tended to occur opposite smaller
      (presumed P), and not larger (presumed M) axon terminals. Only in the K pathway
      in layer IIIB, however, was mGluR5 always found in the axon terminals themselves.
      The presence of mGluR5 in K axons and not in M and P axons, and the presence of
      mGluR5 postsynaptic mainly to smaller P and not larger M axons suggest that the
      response to the release of glutamate is modulated in distinct ways within and
      between the parallel visual pathways of primates.

PMID- 25774087
TI  - Combination medical treatment for primary open angle glaucoma and ocular
      hypertension: a network meta-analysis.
AB  - This is the protocol for a review and there is no abstract. The objectives are as
      follows: The objectives of this review are to examine the comparative
      effectiveness and safety of different glaucoma fixed combination therapies and
      monotherapies in eyes with primary open angle glaucoma or ocular hypertension and
      to provide relative rankings of these treatments.

PMID- 25774088
TI  - Effect of apoptosis in neural stem cells treated with sevoflurane.
AB  - BACKGROUND: At present, sevoflurane inhalation anesthesia used on infants is well
      known. But long-time exposure to inhalation anesthetic could cause neurologic
      disorder, especially nerve degeneration in infant and developing brain. The
      central nervous system degeneration of infants could affect the memory and
      cognitive function. gamma-Aminobutyric acid (GABA) is a known inhibitory
      neurotransmitter in central nervous system. Inhalation anesthetic sevoflurane may
      activate GABAA receptor to inhibit central nervous system, leading to apoptosis
      of neural degeneration, cognitive dysfunction in the critical period of brain
      development. METHODS: Neural stem cells were derived from Wistar embryos,
      cultured in vitro. Third generation of neural stem cells were randomly divided
      into four groups according to cultured suspension: Sevoflurane group (Group S),
      GABAA receptor antagonists, Bicuculline group (Group B), Sevoflurane + GABAA
      receptor antagonists, Bicuculline group (Group S + B), dimethyl sulphoxide (DMSO)
      group (Group D). Group B and Group D did not receive sevoflurane preconditioning.
      Group S and Group S + B were pretreated with 1 minimum alveolar concentration
      (MAC) sevoflurane for 0 h, 3 h, 6 h, and 12 h. Group S + B and Group B were
      pretreated with bicuculline (10 uM). Group D was treated with DMSO (10 uL/mL).
      After treatments above, all groups were cultured for 48 h. Then we measured the
      cells viability by Cell Counting Kit (CCK-8) assay, cytotoxicity by Lactate
      Dehydrogenase (LDH) assay, apoptosis ratio with Annexin V/propidium iodide (PI)
      staining by flow cytometry, and the expression of GABAAR, anti-apoptotic protein
      Bcl-2, pro-apoptotic protein Bax and Caspase-3 by western blotting. RESULTS:
      After exposing to sevoflurane for 0 h, 3 h, 6 h, and 12 h with 1MAC, we found
      that cell viability obviously decreased and cytotoxicity increased in time
      dependent way. And Annexin V/PI staining indicated increased apoptosis ratio by
      flow cytometry. The protein level of GABAA receptor, pro-apoptotic protein Bax
      and apoptosis protein Caspase-3 increased; while anti-apoptotic protein Bcl-2
      decreased. And bicuculline could reverse all detrimental results caused by
      sevoflurane. CONCLUSION: Sevoflurane can inhibit the central nervous system by
      activating GABAA, resulting in apoptosis of neural stem cells, thus leading to
      the NSCs degeneration.

PMID- 25774089
TI  - Predictors of neurological outcomes after successful extracorporeal
      cardiopulmonary resuscitation.
AB  - BACKGROUND: Extracorporeal cardiopulmonary resuscitation (ECPR) refers to use of
      extracorporeal membrane oxygenation (ECMO) in cardiopulmonary arrest. Although
      ECPR can increase survival rates after cardiac arrest, it can also result in poor
      post-resuscitation neurological status. Thus, we investigated predictors of good
      neurological outcomes after successful ECPR. METHODS: A total of 227 patients
      underwent ECPR from May 2004 to June 2013 at Samsung Medical Center. Successful
      ECPR was defined as survival more than 24 hours after ECPR. Neurological outcomes
      were assessed at discharge using the Glasgow-Pittsburgh Cerebral Performance
      Categories scale (CPC). CPC 1 and 2 were classified as good and CPC 3 to 5 were
      classified as poor neurological outcomes. Excluded were 22 patients who did not
      survive more than 24 hours after ECPR and 90 patients who died from unknown
      causes or causes other than brain death or whose neurological status could not be
      assessed at discharge. Multiple logistic regression analysis was used to identify
      independent predictors of neurological outcomes. RESULTS: Included were 115
      patients with a mean age of 58 (range 45-66) years and 80 men (70%).
      Cardiopulmonary resuscitation (CPR) was performed at non-hospital sites for 19
      (17%) patients and bystander CPR was performed in 9 of 19 cases (47%). Cardiac
      etiology was verified in 74 (64%) patients and therapeutic hypothermia was
      performed in 9 patients (8%); 68 (59%) had good neurological outcomes and 47
      (41%) did not and 24 patients died from brain death. Neurological outcomes were
      affected by hemoglobin levels before ECMO (P = 0.02), serum lactic acid (P <
      0.001) before ECMO insertion, and interval from cardiac arrest to ECMO (P =
      0.04). CONCLUSIONS: Low hemoglobin or high serum lactic acid levels before ECMO,
      and prolonged interval from cardiac arrest to ECMO predicted poor neurological
      outcomes after successful ECPR. Early institution of ECMO and a low threshold for
      blood transfusion might improve neurological outcomes for patients who survive
      ECPR.

PMID- 25774090
TI  - Median effective effect-site concentration of sufentanil for wake-up test in
      adolescents undergoing surgery: a randomized trial.
AB  - BACKGROUND: To determine the median effective concentration of sufentanil as an
      analgesic during wake-up tests after sevoflurane anesthesia during surgery for
      adolescent idiopathic scoliosis (AIS). METHODS: This is a randomised controlled
      trial. Sixty patients aged 13-18 years scheduled for AIS surgery were randomized
      into six groups of 10 patients each to receive target effect-site concentrations
      of sufentanil of 0.19, 0.1809, 0.1723, 0.1641, 0.1563, and 0.1489 ng/ml (target
      concentration ratio, 1.05). Wake-up time was recorded. Median EC50 and 95%
      confidence interval (CI) for sufentanil target-controlled infusion (TCI) were
      determined using Karber's method. The primary outcome was median EC50 for
      sufentanil TCI as an analgesic during the wake-up test after sevoflurane
      anesthesia during surgery for AIS. RESULTS: The EC50 and 95% CI of sufentanil TCI
      were 0.1682 ng/ml and 0.1641 ~ 0.1724 ng/ml, respectively. CONCLUSIONS: The EC50
      of sufentanil TCI was 0.1682 ng/ml (95% CI: 0.1641 ~ 0.1724 ng/ml) during
      sevoflurane anesthesia in adolescents undergoing surgery for idiopathic scoliosis
      with intraoperative wake-up tests. TRIAL REGISTRATION: Clinicaltrials.gov
      identifier: ChiCTR-TTRCC-12002696.

PMID- 25774091
TI  - Therapeutic plasma exchange does not reduce vasopressor requirement in severe
      acute liver failure: a retrospective case series.
AB  - BACKGROUND: In acute liver failure (ALF) therapeutic plasma exchange (TPE)
      improves laboratory measures of liver function. In patients with ALF requiring
      minimal vasoactive support TPE has also been shown to provide haemodynamic
      benefits including an increase in systemic blood pressure. However the
      haemodynamic effects of TPE in patients with severe ALF requiring moderate or
      high dose vasopressor therapy has not been reported. We retrospectively examined
      the haemodynamic effects of TPE in a cohort of patients with severe ALF requiring
      vasopressor therapy. METHODS: Physiological, laboratory and treatment data were
      collected on all patients with ALF who received TPE between January 2000 and
      December 2012. All patients were managed in the intensive care unit of a tertiary
      referral centre for ALF and liver transplantation. The primary outcome measures
      were changes in mean arterial pressure (MAP), vasopressor score and the ratio of
      vasopressor score to MAP (vasopressor dependency index (VDI)) from baseline prior
      to TPE through to 12 hours after completion of TPE. Secondary outcome measures
      were changes in other routinely collected physiological variables and laboratory
      results. Results are presented as median (interquartile range (IQR)). Outcome
      measures were evaluated using a mixed effect model. RESULTS: Thirty nine TPE were
      performed in 17 patients with ALF (13 paracetamol poisoning). All TPE were
      performed with a centrifugal apheresis system (duration 130 minutes (IQR 115 -
      147.5), plasma volume removed 5.1% body weight (IQR 4.6 - 5.5). Baseline values
      for primary outcome measures were: MAP 82 mmHg (IQR 72 - 92.5), vasopressor score
      8.35 (IQR 3.62 - 24.6) and VDI 0.10 (IQR 0.05 - 0.31). MAP was significantly
      higher immediately after TPE compared to baseline (p = 0.039), however when
      corrected for change in vasopressor requirement there was no significant change
      in VDI with TPE (p = 0.953). Twelve hours after TPE the MAP, vasopressor score
      and VDI were not significantly different from baseline (p = 0.563, p = 0.317 and
      p = 0.214 respectively). CONCLUSION: In this cohort of patients with severe ALF
      centrifugal TPE did not significantly affect vasopressor requirements.

PMID- 25774092
TI  - Primary gastric actinomycosis: report of a case diagnosed in a gastroscopic
      biopsy.
AB  - BACKGROUND: Primary gastric actinomycosis is extremely rare, the appendix and
      ileocecal region being the most commonly involved sites in abdominopelvic
      actinomycosis. Herein, we report a case of primary gastric actinomycosis. The
      diagnosis was made on microscopic evaluation of gastroscopic biopsy specimens. To
      the best of our knowledge, this is the third case to be reported in the
      literature, in which the diagnosis was made in a gastroscopic biopsy rather than
      a resection specimen. CASE PRESENTATION: An 87-year-old Saudi male on medication
      for cardiomyopathy, premature ventricular contractions, renal impairment,
      hypertension, and dyslipidemia, presented to the emergency department with acute
      diffuse abdominal pain, abdominal distension, constipation and vomiting for two
      days, with no history of fever, abdominal surgery or trauma. The patient was
      admitted to the hospital with an impression of gastric outlet obstruction. Based
      on radiologic and gastroscopic findings, a non-infectious etiology was suspected,
      possibly adenocarcinoma or lymphoma. Gastroscopic biopsies showed an actively
      inflamed, focally ulcerated atrophic fundic mucosa along with fragments of a
      fibrinopurulent exudate containing brownish, iron negative pigment and abundant
      filamentous bacteria, morphologically consistent with Actinomyces. CONCLUSION:
      Althuogh extremely rare, primary gastric actinomycosis should be considered in
      the differential diagnosis of radiologic and gastroscopic diffuse gastric wall
      thickening and submucosal tumor-like or infiltrative lesions, particularly in
      patients with history of abdominal surgery or trauma, or those receiving
      extensive medication. A high level of suspicion is required by the pathologist to
      achieve diagnosis in gastroscopic biopsies. Subtle changes such as the presence
      of a pigmented inflammatory exudate should alert the pathologist to perform
      appropriate special stains to reveal the causative organism.

PMID- 25774093
TI  - Transient knockdown-mediated deficiency in plectin alters hepatocellular motility
      in association with activated FAK and Rac1-GTPase.
AB  - BACKGROUND: Plectin is one of the cytolinker proteins that play a crucial role in
      maintaining the integrity of cellular architecture. It is a component of
      desmosome complexes connecting cytoskeletal proteins and trans-membrane
      molecules. In epithelial cells, plectin connects cytokeratins and integrin
      alpha6beta4 in hemidesmosomes anchoring to the extracellular matrix. In addition
      to the function of molecular adherent, plectin has been reported to exhibit
      functions affecting cellular signals and responsive activities mediated by
      stress, cellular migration, polarization as well as the dynamic movement of actin
      filaments. Plectin deficiency in hepatocellular carcinoma results in abnormal
      expression of cytokeratin 18 and disassembled hemidesmosome. Therefore, it is
      hypothesized that the plectin deficiency-mediated collapse of cytoskeleton may
      modulate cellular motility that is associated with consequent metastatic
      behaviors of cancer cells. METHODS AND RESULTS: The cellular motility of plectin
      deficient Chang liver cells generated by transient knockdown were analyzed by
      trans-well migration assay and the results revealed a higher migration rate. The
      confocal microscopy also demonstrated less organized and more polarized
      morphology as well as more focal adhesion kinase activity in comparison with that
      of the mock Chang liver cells. Furthermore, plectin-knockdown in Chang liver
      cells was associated with a higher activity of Rac1-GTPase in accordance with the
      results of the Rac1 pull-down assay. The immunohistochemical assay on human
      hepatocellular carcinoma showed that the expression of focal adhesion kinase was
      increased in the invasive front of tumor. CONCLUSION: Plectin-deficient human
      hepatic cells exhibit higher cell motility associated with increase in focal
      adhesion kinase activity that are comparable to the properties of invasive
      hepatocellular carcinoma.

PMID- 25774095
TI  - Recombinase-mediated cassette exchange (RMCE) system for functional genomics
      studies in Mycoplasma mycoides.
AB  - BACKGROUND: We have previously established technologies enabling us to engineer
      the Mycoplasma mycoides genome while cloned in the yeast Saccharomyces
      cerevisiae, followed by genome transplantation into Mycoplasma capricolum
      recipient cells to produce M. mycoides with an altered genome. To expand the
      toolbox for genomic modifications, we designed a strategy based on the Cre/loxP
      based Recombinase-Mediated Cassette Exchange (RMCE) system for functional
      genomics analyses. RESULTS: In this paper, we demonstrated replacement of an
      approximately 100 kb DNA segment of the M. mycoides genome with a synthetic DNA
      counterpart in two orientations. The function of the altered genomes was then
      validated by genome transplantation and phenotypic characterization of the
      transplanted cells. CONCLUSION: This method offers an easy and efficient way to
      manipulate the M. mycoides genome and will be a valuable tool for functional
      genomic studies, such as genome organization and minimization.

PMID- 25774094
TI  - Anatomical, functional and molecular biomarker applications of magnetic resonance
      neuroimaging.
AB  - MRI and magnetic resonance spectroscopy (MRS) along with computed tomography and
      PET are the most common imaging modalities used in the clinics to detect
      structural abnormalities and pathological conditions in the brain. MRI generates
      superb image resolution/contrast without radiation exposure that is associated
      with computed tomography and PET; MRS and spectroscopic imaging technologies
      allow us to measure changes in brain biochemistry. Increasingly, neurobiologists
      and MRI scientists are collaborating to solve neuroscience problems across sub
      cellular through anatomical levels. To achieve successful cross-disciplinary
      collaborations, neurobiologists must have sufficient knowledge of magnetic
      resonance principles and applications in order to effectively communicate with
      their MRI colleagues. This review provides an overview of magnetic resonance
      techniques and how they can be used to gain insight into the active brain at the
      anatomical, functional and molecular levels with the goal of encouraging
      neurobiologists to include MRI/MRS as a research tool in their endeavors.

PMID- 25774096
TI  - Evaluation of Epic(r) label-free technology to quantify functional recombinant
      hemagglutinin.
AB  - BACKGROUND: Alternative methods are being sought to measure the potency of
      influenza vaccines. Label-free technologies that do not require the use of
      hemagglutinin (HA)-specific antisera are particularly attractive as the
      preparation of antiserum delays availability of potency reagents. The objective
      of these experiments was to evaluate the use of a Corning Epic(r) label-free
      method to quantify functional influenza hemagglutinin in rHA preparations. The
      method was optimized to quantify recombinant HA (rHA) of B/Brisbane/60/2008
      (B/BR/08). Fetuin was immobilized onto plates and the change in wavelength of
      refracted light measured using an Enspire (Perkin Elmer) instrument. RESULTS: The
      change in wavelength measured in response to addition of rHA of B/BR/08 was
      proportional to its concentration and was optimal in the presence of native rHA
      conformations. However, the assay was strain-dependent and did not correlate with
      HAU measured using turkey red blood cells. CONCLUSIONS: The Corning Epic(r) label
      free method is suitable for quantifying the native forms of rHA for B/BR/08 and
      A/Brisbane/59/2007 (H1N1) and A/Hangxhou/3/2013 (H7N9). This method is a useful
      tool for research purposes but further investigation is needed to identify
      suitable glycoproteins to use as ligands that allow quantification of HAs from a
      broader range of virus strains.

PMID- 25774097
TI  - Volunteerism and Well-Being in the Context of the World Trade Center Terrorist
      Attacks.
AB  - Using a community sample of New York City residents (N=1681) interviewed 1 and 2
      years after the World Trade Center Disaster (WTCD), we estimated several logistic
      regression equations to assess predictors of volunteerism and the relationship
      between volunteerism and later well-being. Multivariate results show that those
      with more education, higher exposure to WTCD events, many life-time traumatic
      events, and pre-WTCD mental health problems were more likely to report
      volunteerism post-WTCD. African Americans and Latinos were less likely to
      volunteer, compared to Whites. Respondents scoring high on the Srole Anomie scale
      and reporting physical disabilities were also less likely to report volunteering
      in the aftermath of the WTCD. Multivariate results with volunteerism as an
      independent variable suggest that people who engaged in this activity were less
      likely to have poor well-being as measured by the SF-12 physical and mental
      health scales. We discuss these results as they relate to identity theory, the
      stress process model, and resilience and how community disaster researchers need
      to pay closer attention to how people interpret and give meaning to traumatic
      events.

PMID- 25774098
TI  - Continuous Crystallization of Proteins in a Tubular Plug-Flow Crystallizer.
AB  - Protein crystals have many important applications in many fields, including
      pharmaceutics. Being more stable than other formulations, and having a high
      degree of purity and bioavailability, they are especially promising in the area
      of drug delivery. In this contribution, the development of a continuously
      operated tubular crystallizer for the production of protein crystals has been
      described. Using the model enzyme lysozyme, we successfully generated product
      particles ranging between 15 and 40 MUm in size. At the reactor inlet, a protein
      solution was mixed with a crystallization agent solution to create high
      supersaturations required for nucleation. Along the tube, supersaturation was
      controlled using water baths that divided the crystallizer into a nucleation zone
      and a growth zone. Low flow rates minimized the effect of shear forces that may
      impede crystal growth. Simultaneously, a slug flow was implemented to ensure
      crystal transport through the reactor and to reduce the residence time
      distribution.

PMID- 25774099
TI  - Cultural Competency Education for Researchers: A Pilot Study Using a Neighborhood
      Visit Approach.
AB  - BACKGROUND: Little attention has been given to the cultural competence education
      needs for researchers. OBJECTIVES: To describe the planning and implementation of
      a neighborhood visit approach to cultural competency education in the community.
      METHODS: A committee of community partners and academics planned, conducted and
      evaluated the visit. The cultural competence and confidence (CCC) model was used
      to engage researchers. An evaluation survey assessed participant satisfaction and
      experiences. RESULTS: Of the 74 attendees 64 (84%) completed the conference
      evaluation. Attendees expressed that the visit and conference objectives were met
      and that the content was relevant to their work. Nearly all (95%) responded they
      would incorporate what they learned into practice. CONCLUSION: A neighborhood
      visit approach is feasible and acceptable to researchers and community partners.
      Evaluation of this community based education program showed preliminary evidence
      of changing both the way researchers think about the community and conduct
      research.

PMID- 25774100
TI  - Distress and Resilience After Cancer in Veterans.

PMID- 25774102
TI  - Uncertainty analysis for absorption and first-derivative EPR spectra.
AB  - Electron paramagnetic resonance (EPR) experimental techniques produce absorption
      or first-derivative spectra. Uncertainty analysis provides the basis for
      comparison of spectra obtained by different methods. In this study it was used to
      derive analytical equations to relate uncertainties for integrated intensity and
      line widths obtained from absorption or first-derivative spectra to the signal-to
      noise ratio (SNR), with the assumption of white noise. Predicted uncertainties
      for integrated intensities and line widths are in good agreement with Monte Carlo
      calculations for Lorentzian and Gaussian lineshapes. Conservative low-pass
      filtering changes the noise spectrum, which can be modeled in the Monte Carlo
      simulations. When noise is close to white, the analytical equations provide
      useful estimates of uncertainties. For example, for a Lorentzian line with white
      noise, the uncertainty in the number of spins obtained from the first-derivative
      spectrum is 2.6 times greater than from the absorption spectrum at the same SNR.
      Uncertainties in line widths obtained from absorption and first-derivative
      spectra are similar. The impact of integration or differentiation on SNR and on
      uncertainties in fitting parameters was analyzed. Although integration of the
      first-derivative spectrum improves the apparent smoothness of the spectrum, it
      also changes the frequency distribution of the noise. If the lineshape of the
      signal is known, the integrated intensity can be determined more accurately by
      fitting the first-derivative spectrum than by first integrating and then fitting
      the absorption spectrum. Uncertainties in integrated intensities and line widths
      are less when the parameters are determined from the original data than from
      spectra that have been either integrated or differentiated.

PMID- 25774101
TI  - Enthesitis as a component of dactylitis in psoriatic juvenile idiopathic
      arthritis: histology of an established clinical entity.
AB  - CONTEXT: Imaging of dactylitis in adult psoriatic arthritis suggests a
      pathophysiological role for enthesitis. However, histological definition of the
      dactylitic digit is unavailable. OBJECTIVE: We evaluated the role of enthesitis
      in dactylitis associated with psoriatic juvenile idiopathic arthritis (psJIA) in
      a child who underwent detailed imaging and histologic evaluation. DESIGN:
      Radiographs, ultrasound and high-resolution magnetic resonance imaging were
      employed to define the locus of disease in two dactylitic digits from a 14-year
      old girl with psJIA. Biopsies were stained with hematoxylin and eosin, CD3, CD20,
      CD4, CD8 and CD117 and examined via light microscopy. RESULTS: Radiologic
      features of dactylitis included enhanced signal at digital entheses without
      accompanying synovitis or tenosynovitis. Histologically, finger and toe tissue
      exhibited hypervascular tenosynovium with a fibromyxoid expansion of fibrous
      tissue. This was accompanied by sparse to moderate perivascular lymphocytic
      inflammation consisting predominantly of T cells, with occasional admixed B cells
      and mast cells. Neutrophils and plasma cells were absent. Fibrocartilage
      exhibited reactive features including increased extracellular myxoid matrix,
      binucleation, and focal necrosis, without cellular inflammation. Fibrinous
      synovitis and mild reactive synoviocyte hyperplasia were seen. CONCLUSIONS:
      Dactylitis in psJIA bears a radiographic resemblance to the condition in adult
      psoriatic arthritis. Histologic hallmarks include an expanded mast cell-populated
      extracellular myxoid matrix, cartilage degeneration, and a T cell-rich
      perivascular inflammatory infiltrate. These findings help to define enthesitis as
      a clinicopathologic entity.

PMID- 25774103
TI  - Allium ursinum: botanical, phytochemical and pharmacological overview.
AB  - Ramson-Allium ursinum L. is a medicinal and dietary plant species with a long
      tradition of use. This mini-review summarizes the current knowledge on the
      phytochemistry and pharmacological properties of this valuable plant, with
      special emphasis on antimicrobial, cytotoxic, antioxidant, and cardio-protective
      effects.

PMID- 25774104
TI  - Combining DI-ESI-MS and NMR datasets for metabolic profiling.
AB  - Metabolomics datasets are commonly acquired by either mass spectrometry (MS) or
      nuclear magnetic resonance spectroscopy (NMR), despite their fundamental
      complementarity. In fact, combining MS and NMR datasets greatly improves the
      coverage of the metabolome and enhances the accuracy of metabolite
      identification, providing a detailed and high-throughput analysis of metabolic
      changes due to disease, drug treatment, or a variety of other environmental
      stimuli. Ideally, a single metabolomics sample would be simultaneously used for
      both MS and NMR analyses, minimizing the potential for variability between the
      two datasets. This necessitates the optimization of sample preparation, data
      collection and data handling protocols to effectively integrate direct-infusion
      MS data with one-dimensional (1D) 1H NMR spectra. To achieve this goal, we report
      for the first time the optimization of (i) metabolomics sample preparation for
      dual analysis by NMR and MS, (ii) high throughput, positive-ion direct infusion
      electrospray ionization mass spectrometry (DI-ESI-MS) for the analysis of complex
      metabolite mixtures, and (iii) data handling protocols to simultaneously analyze
      DI-ESI-MS and 1D 1H NMR spectral data using multiblock bilinear factorizations,
      namely multiblock principal component analysis (MB-PCA) and multiblock partial
      least squares (MB-PLS). Finally, we demonstrate the combined use of backscaled
      loadings, accurate mass measurements and tandem MS experiments to identify
      metabolites significantly contributing to class separation in MB-PLS-DA scores.
      We show that integration of NMR and DI-ESI-MS datasets yields a substantial
      improvement in the analysis of neurotoxin involvement in dopaminergic cell death.

PMID- 25774105
TI  - Antimicrobial cyclic peptides for plant disease control.
AB  - Antimicrobial cyclic peptides derived from microbes bind stably with target
      sites, have a tolerance to hydrolysis by proteases, and a favorable degradability
      under field conditions, which make them an attractive proposition for use as
      agricultural fungicides. Antimicrobial cyclic peptides are classified according
      to the types of bonds within the ring structure; homodetic, heterodetic, and
      complex cyclic peptides, which in turn reflect diverse physicochemical features.
      Most antimicrobial cyclic peptides affect the integrity of the cell envelope.
      This is achieved through direct interaction with the cell membrane or disturbance
      of the cell wall and membrane component biosynthesis such as chitin, glucan, and
      sphingolipid. These are specific and selective targets providing reliable
      activity and safety for non-target organisms. Synthetic cyclic peptides produced
      through combinatorial chemistry offer an alternative approach to develop
      antimicrobials for agricultural uses. Those synthesized so far have been studied
      for antibacterial activity, however, the recent advancements in powerful
      technologies now promise to provide novel antimicrobial cyclic peptides that are
      yet to be discovered from natural resources. 

PMID- 25774106
TI  - Molecular Screening of Blast Resistance Genes in Rice using SSR Markers.
AB  - Rice Blast is the most devastating disease causing major yield losses in every
      year worldwide. It had been proved that using resistant rice varieties would be
      the most effective way to control this disease. Molecular screening and genetic
      diversities of major rice blast resistance genes were determined in 192 rice
      germplasm accessions using simple sequence repeat (SSR) markers. The genetic
      frequencies of the 10 major rice blast resistance genes varied from 19.79% to
      54.69%. Seven accessions IC337593, IC346002, IC346004, IC346813, IC356117,
      IC356422 and IC383441 had maximum eight blast resistance gene, while FR13B,
      Hourakani, Kala Rata 1-24, Lemont, Brown Gora, IR87756-20-2-2-3, IC282418,
      IC356419, PKSLGR-1 and PKSLGR-39 had seven blast resistance genes. Twenty
      accessions possessed six genes, 36 accessions had five genes, 41 accessions had
      four genes, 38 accessions had three genes, 26 accessions had two genes, 13
      accessions had single R gene and only one accession IC438644 does not possess any
      one blast resistant gene. Out of 192 accessions only 17 accessions harboured 7 to
      8 blast resistance genes. 

PMID- 25774107
TI  - Development of PCR and TaqMan PCR Assays to Detect Pseudomonas coronafaciens, a
      Causal Agent of Halo Blight of Oats.
AB  - Pseudomonas coronafaciens causes halo blight on oats and is a plant quarantine
      bacterium in many countries, including the Republic of Korea. Using of the
      certificated seed is important for control of the disease. Since effective
      detection method of P. coronafaciens is not available yet, PCR and TaqMan PCR
      assays for specific detection of P. coronafaciens were developed in this study.
      PCR primers were designed from the draft genome sequence of P. coronafaciens LMG
      5060 which was obtained by the next-generation sequencing in this study. The PCR
      primer set Pc-12-F/Pc-12-R specifically amplified 498 bp from the 13 strains of
      P. coronafaciens isolated in the seven different countries (Canada, Japan, United
      Kingdom, Zimbabwe, Kenya, Germany, and New Zealand) and the nested primer set Pc
      12-ne-F/Pc-12-ne-R specifically amplified 298 bp from those strains. The target
      size PCR product was not amplified from the non-target bacteria with the PCR and
      nested primer sets. TaqMan PCR with Pc-12-ne-F/Pc-12-ne-R and a TaqMan probe, Pc
      taqman, which were designed inside of the nested PCR amplicon, generated Ct
      values which in a dose-dependent manner to the amount of the target DNA and the
      Ct values of all the P. coronafaciens strains were above the threshold Ct value
      for positive detection. The TaqMan PCR generated positive Ct values from the seed
      extracts of the artificially inoculated oat seeds above 10 cfu/ml inoculation
      level. PCR and TaqMan PCR assays developed in this study will be useful tools to
      detect and identify the plant quarantine pathogen, P. coronafaciens. 

PMID- 25774108
TI  - Identification of Coupling and Repulsion Phase DNA Marker Associated With an
      Allele of a Gene Conferring Host Plant Resistance to Pigeonpea sterility mosaic
      virus (PPSMV) in Pigeonpea (Cajanus cajan L. Millsp.).
AB  - Pigeonpea Sterility Mosaic Disease (PSMD) is an important foliar disease caused
      by Pigeonpea sterility mosaic virus (PPSMV) which is transmitted by eriophyid
      mites (Aceria cajani Channabasavanna). In present study, a F2 mapping population
      comprising 325 individuals was developed by crossing PSMD susceptible genotype
      (Gullyal white) and PSMD resistant genotype (BSMR 736). We identified a set of 32
      out of 300 short decamer random DNA markers that showed polymorphism between
      Gullyal white and BSMR 736 parents. Among them, eleven DNA markers showed
      polymorphism including coupling and repulsion phase type of polymorphism across
      the parents. Bulked Segregant Analysis (BSA), revealed that the DNA marker,
      IABTPPN7, produced a single coupling phase marker (IABTPPN7414) and a repulsion
      phase marker (IABTPPN7983) co-segregating with PSMD reaction. Screening of 325 F2
      population using IABTPPN7 revealed that the repulsion phase marker, IABTPPN7983,
      was co-segregating with the PSMD responsive SV1 at a distance of 23.9 cM for
      Bidar PPSMV isolate. On the other hand, the coupling phase marker IABTPPN7414 did
      not show any linkage with PSMD resistance. Additionally, single marker analysis
      both IABTPPN7983 (P<0.0001) and IABTPPN 7414 (P<0.0001) recorded a significant
      association with the PSMD resistance and explained a phenotypic variance of 31
      and 36% respectively in F2 population. The repulsion phase marker, IABTPPN7983,
      could be of use in Marker-Assisted Selection (MAS) in the PPSMV resistance
      breeding programmes of pigeonpea. 

PMID- 25774109
TI  - Genetic Diversity in the Coat Protein Genes of Prune dwarf virus Isolates from
      Sweet Cherry Growing in Turkey.
AB  - Sweet cherry is an important fruit crop with increasing economical value in
      Turkey and the world. A number of viruses cause diseases and economical losses in
      sweet cherry. Prune dwarf virus (PDV), is one of the most common viruses of stone
      fruits including sweet cherry in the world. In this study, PDV was detected from
      316 of 521 sweet cherry samples collected from 142 orchards in 10 districts of
      Isparta province of Turkey by double antibody sandwich-enzyme linked
      immunosorbent assay (DAS-ELISA). The presence of PDV in ELISA positive samples
      was confirmed in 37 isolates by reverse transcription- polymerase chain reaction
      (RT-PCR) method. A genomic region of 862 bp containing the coat protein (CP) gene
      of PDV was re-amplified from 21 selected isolates by RT-PCR. Amplified DNA
      fragments of these isolates were purified and sequenced for molecular
      characterization and determining genetic diversity of PDV. Sequence comparisons
      showed 84-99% to 81-100% sequence identity at nucleotide and amino acid level,
      respectively, of the CP genes of PDV isolates from Isparta and other parts of the
      world. Phylogenetic analyses of the CP genes of PDV isolates from different
      geographical origins and diverse hosts revealed that PDV isolates formed
      different phylogenetic groups. While isolates were not grouped solely based on
      their geographical origins or hosts, some association between phylogenetic groups
      and geographical origins or hosts were observed. 

PMID- 25774110
TI  - Characterization of Novel Trichoderma asperellum Isolates to Select Effective
      Biocontrol Agents Against Tomato Fusarium Wilt.
AB  - The use of novel isolates of Trichoderma with efficient antagonistic capacity
      against Fusarium oxysporum f. sp. lycopersici (FOL) is a promising alternative
      strategy to pesticides for tomato wilt management. We evaluated the antagonistic
      activity of 30 isolates of T. asperellum against 4 different isolates of FOL. The
      production of extracellular cell wall degrading enzymes of the antagonistic
      isolates was also measured. The random amplified polymorphic DNA (RAPD) method
      was applied to assess the genetic variability among the T. asperellum isolates.
      All of the T. asperellum isolates significantly reduced the mycelial growth of
      FOL isolates but the amount of growth reduction varied significantly as well.
      There was a correlation between the antagonistic capacity of T. asperellum
      isolates towards FOL and their lytic enzyme production. Isolates showing high
      levels of chitinase and beta-1,3-glucanase activities strongly inhibited the
      growth of FOL isolates. RAPD analysis showed a high level of genetic variation
      among T. asperellum isolates. The UPGMA dendrogram revealed that T. asperellum
      isolates could not be grouped by their anta- gonistic behavior or lytic enzymes
      production. Six isolates of T. asperellum were highly antagonistic towards FOL
      and potentially could be used in commercial agriculture to control tomato wilt.
      Our results are consistent with the conclusion that understanding the genetic
      variation within Trichoderma isolates and their biochemical capabilities are
      required for the selection of effective indigenous fungal strains for the use as
      biocontrol agents. 

PMID- 25774111
TI  - Antifungal Action of Ginkgo biloba Outer Seedcoat on Rice Sheath blight.
AB  - From study of antifungal actions on the rice sheath blight by using the extract
      of Ginkgo biloba outer seedcoats, we found that the extracts of Ginkgo biloba
      outer seedcoats of all treatment concentrations had inhibited the rice sheath
      blight. Among them, the most effective concentration was 250 mg/l at which the
      growth of microbe was 26 mm and even at the packaging test, when sprayed the G.
      biloba outer seedcoats at the level of 250 mg/l, the damage rate of the rice
      sheath blight was identified as 13%. As a result investigating the antifungal
      activity by separating polysaccharides from G. biloba outer seedcoats, it showed
      that the clear zone of 14 mm or more was formed at the concentration of 250 mg/l
      or higher. Based on these results, we concluded that the G. biloba outer seedcoat
      is a natural substance with the antifungal activity on the rice sheath blight. 

PMID- 25774112
TI  - Stem Rot on Adzuki Bean (Vigna angularis) Caused by Rhizoctonia solani AG 4 HGI
      in China.
AB  - During late August and early September 2011, stem rot symptoms were observed on
      adzuki bean plants (Vigna angularis) growing in fields located in Beijing and
      Hebei Province, China, respectively. In this study, four isolates were obtained
      from infected stems of adzuki bean plants. Based on their morphology, and
      sequence and polymerase chain reaction-restriction fragment length polymorphism
      (PCR-RFLP) analyses of the ribosomal DNA internal transcribed spacers (rDNA-ITS)
      region, the four isolates were identified as Rhizoctonia solani in anastomosis
      group (AG) 4 HGI. Pathogenicity tests showed that all isolates were strongly
      pathogenic to adzuki bean and resulted in serious wilt symptoms which was similar
      to observations in the fields. Additionally, the isolates infected several other
      crops and induced related rot on the roots and basal stems. To our knowledge,
      this is the first report of Rhizoctonia solani AG 4 HGI causing stem rot on
      adzuki bean. 

PMID- 25774113
TI  - Accumulation of Transcripts Abundance after Barley Inoculation with Cochliobolus
      sativus.
AB  - Spot blotch caused by the hemibiotrophic pathogen Cochliobolus sativus has been
      the major yield-reducing factor for barley production during the last decade.
      Monitoring transcriptional reorganization triggered in response to this fungus is
      an essential first step for the functional analysis of genes involved in the
      process. To characterize the defense responses initiated by barley resistant and
      susceptible cultivars, a survey of transcript abundance at early time points of
      C. sativus inoculation was conducted. A notable number of transcripts exhibiting
      significant differential accumulations in the resistant and susceptible cultivars
      were detected compared to the non-inoculated controls. At the p-value of 0.0001,
      transcripts were divided into three general categories; defense, regulatory and
      unknown function, and the resistant cultivar had the greatest number of common
      transcripts at different time points. Quantities of differentially accumulated
      gene transcripts in both cultivars were identified at 24 h post infection, the
      approximate time when the pathogen changes trophic lifestyles. The unique and
      common accumulated transcripts might be of considerable interest for enhancing
      effective resistance to C. sativus. 

PMID- 25774114
TI  - Occurrence of Leaf Blight on Cosmos Caused by Alternaria cosmosa in Korea.
AB  - In 2011, a leaf blight disease was observed on cosmos (Cosmos bipinnatus) leaves
      in Nonsan, Korea. The causal pathogen was isolated and identified based on
      morphological and molecular approaches. Morphological characteristics of the
      pathogen matched well with the Alternaria cosmosa and also easily distinguishable
      from Alternaria zinniae reported from cosmos seeds by producing branched beak.
      Phylogenetically, the pathogen could not be distinguished from A. passiflorae
      based on the sequence analysis of a combined data set of Alt a1 and gpd genes.
      However, A. passiflorae was distinguished from the present species by having
      conidiophores with 4 to 5 conidiogenous loci. The results indicate that the
      present Alternaria species is A. cosmosa. Pathogenicity tests revealed that the
      isolate was pathogenic to the leaves of Cosmos bipinnatus. This is the first
      report of Alternaria blight disease caused by A. cosmosa on cosmos in Korea. 

PMID- 25774115
TI  - Isolation and Genomic Characterization of the T4-Like Bacteriophage PM2 Infecting
      Pectobacterium carotovorum subsp. carotovorum.
AB  - In order to control Pectobacterium carotovorum subsp. carotovorum, a novel
      virulent bacteriophage PM2 was isolated. Bacteriophage PM2 can infect 48% of P.
      carotovorum subsp. carotovorum and 78% of P. carotovorum subsp. brasilliensis but
      none of atrosepticum, betavasculorum, odoriferum and wasabiae isolates had been
      infected with PM2. PM2 phage belongs to the family Myoviridae, and contains a
      large head and contractile tail. It has a 170,286 base pair genome that encodes
      291 open reading frames (ORFs) and 12 tRNAs. Most ORFs in bacteriophage PM2 share
      a high level of homology with T4-like phages including IME08, RB69, and JS98.
      Phylogenetic analysis based on the amino acid sequence of terminase large
      subunits confirmed that PM2 is classified as a T4-like phage. It contains no
      integrase- or no repressor-coding genes related to the lysogenic cycle, and
      lifestyle prediction using PHACT software suggested that PM2 is a virulent
      bacteriophage. 

PMID- 25774116
TI  - Development of multiplex rt-PCR for simultaneous detection of garlic viruses and
      the incidence of garlic viral disease in garlic genetic resources.
AB  - Garlic generally becomes coinfected with several types of viruses belonging to
      the Potyvirus, Carlavirus, and Allexivirus genera. These viruses produce
      characteristically similar symptoms, they cannot be easily identified by electron
      microscopy (EM) or immunological detection methods, and they are currently
      widespread around the world, thereby affecting crop yields and crop quality
      adversely. For the early and reliable detection of garlic viruses, virus-specific
      sets of primers, including species-specific and genus-specific primers were
      designed. To effectively detect the twelve different types of garlic viruses,
      primer mixtures were tested and divided into two independent sets for multiplex
      polymerase chain reaction (PCR). The multiplex PCR assays were able to detect
      specific targets up to the similar dilution series with monoplex reverse
      transcription (RT)-PCR. Seventy-two field samples collected by the Gyeongbuk
      Agricultural Technology Administration were analyzed by multiplex RT-PCR. All
      seventy two samples were infected with at least one virus, and the coinfection
      rate was 78%. We conclude that the simultaneous detection system developed in
      this study can effectively detect and differentiate mixed viral infections in
      garlic. 

PMID- 25774117
TI  - Reducing the Harms of College Student Drinking: How Alan Marlatt Changed
      Approaches, Outcomes, and the Field.
AB  - In this article, we discuss Alan Marlatt's contributions to the prevention and
      reduction of alcohol-related harms among college students. We consider Alan's
      early research that later led to the development and evaluation of college
      student drinking programs, and examine Alan's impact, both directly and
      indirectly through those he mentored and trained, as a scientist-practitioner. We
      review the recognition of the efficacy of Alan's programs, including the Alcohol
      Skills Training Program (ASTP) and Brief Alcohol Screening and Intervention for
      College Students (BASICS), in addition to extensions of these interventions in
      more recent studies. Finally, we discuss how Alan's work influences interventions
      with college student drinkers today, and how future directions will continue to
      be informed by his vision and values.

PMID- 25774118
TI  - Options on fibroid morcellation: a literature review.
AB  - In laparoscopy, specimens have to be removed from the abdominal cavity. If the
      trocar opening or the vaginal outlet is insufficient to pass the specimen, the
      specimen needs to be reduced. The power morcellator is an instrument with a fast
      rotating cylindrical knife which aims to divide the tissue into smaller pieces or
      fragments. The Food and Drug Administration (FDA) issued a press release in April
      2014 that discouraged the use of these power morcellators. This article has the
      objective to review the literature related to complications by power morcellation
      of uterine fibroids in laparoscopy and offer recommendations to laparoscopic
      surgeons in gynaecology. This project was initiated by the executive board of the
      European Society of Gynaecological Endoscopy. A steering committee on fibroid
      morcellation was installed and experienced ESGE members requested to chair an
      action group to address distinct clinical questions. Clinical questions were
      formulated with regards to the sarcoma risk in presumed uterine fibroids,
      diagnosis of sarcoma, complications of morcellation and future research. A
      literature review on the different subjects was conducted, systematic if
      appropriate and feasible. It was concluded that the true prevalence of uterine
      sarcoma in presumed fibroids is not known given the wide range of prevalences
      (0.45-0.014 %) from meta-analyses mainly based on retrospective trials. Age and
      certain imaging characteristics such as 'lacunes' suggesting necrosis and
      increased central vascularisation of the tumour are associated with a higher risk
      of uterine sarcoma, although the risks remain low. There is not enough evidence
      to estimate this risk in individual patients. Complications of morcellation are
      rare. Reported are direct morcellation injuries to vessels and bowel, the
      development of so-called parasitic fibroids requiring reintervention and the
      spread of sarcoma cells in the abdominal cavity, which may possibly or even
      likely upstaging the disease. Momentarily in-bag morcellation is investigated as
      it may possibly prevent morcellation complications. Because of lack of evidence,
      this literature review cannot give strong recommendations but offers only options
      which are condensed in a flow chart. Prospective data collection may clarify the
      issue on sarcoma risk in presumed fibroids and technology to extract tissue
      laparoscopically from the abdominal cavity should be perfected.

PMID- 25774119
TI  - Ovarian endometrioma in the adolescent: a plea for early-stage diagnosis and full
      surgical treatment.
AB  - The incidence and severity of endometriosis in adolescent are comparable with the
      incidence in adult women. The mean delay between the onset of symptoms and the
      final diagnosis varies between 6.4 and 11.7 years. The longer the diagnosis is
      delayed, the more the endometriosis can progress to a more severe stage certainly
      in the group of patients with pelvic pain. The evolution of endometriosis and its
      progressivity are not predictable, and the severity of the disease is not
      directly related to the degree of pain. Endometriotic cysts have a detrimental
      effect on the ovarian reserve by the evolution in time and the surgical excision
      technique. Already, in small endometriotic cysts (<4 cm), loss of follicular
      reserve is present together with the formation of fibrosis in the cortex of the
      ovary. Early diagnosis of endometriosis in the adolescent deserves our full
      attention. Non-invasive imaging techniques like 2-D and 3-D ultrasound are
      helpful in the early diagnosis. Early ablative surgery is recommendable. Although
      laparoscopy is traditionally recommended, transvaginal laparoscopy has been shown
      to be most effective in ablating endometriomas with a maximum diameter of 3 cm.
      Early detection and intervention will contribute to a better quality of life in
      these adolescents and also to a lower damage of the ovarian tissue by a less
      invasive ablative surgery.

PMID- 25774120
TI  - Transvaginal hysterotomy for cesarean scar pregnancy in 40 consecutive cases.
AB  - To propose a novel procedure as a safe and effective treatment for cesarean scar
      pregnancy (CSP), a cohort study was initiated in patients diagnosed with CSP and
      treated with transvaginal hysterotomy from December 2009 to March 2013, either as
      a primary or secondary therapy. All diagnoses were confirmed by both sonography
      and pathology, either a gestational sac or residual tissue after termination of
      pregnancy or miscarriage in the cesarean section scar. Basic clinical
      characteristics and perioperative data were collected and analyzed. A total of 40
      patients were included. The mean age was 32.88 +/- 4.55 years. The mean size of
      gestational sacs of the CSP mass at diagnosis was 33.78 +/- 13.14 mm. Mean serum
      beta-hCG level at diagnosis was 47379.73 +/- 45285.10 IU/L. Mean operative time
      was 57.25 +/- 24.52 min. Mean postoperative hemoglobin drop was 1.635 +/- 0.906
      g/dL. Complications were one case of bacteremia and two cases of hematoma. Mean
      hospital stay after surgery was 4.95 +/- 2.62 days. Mean serum beta-hCG levels
      decreased by 88.5, 93.5, and 96.5 % at postoperative day 2, 4, and 6,
      respectively. All patients' beta-hCG levels returned to normal range within 1
      month after surgery. Transvaginal hysterotomy with removal of ectopic pregnancy
      tissue and repair of cesarean scar defect is a promising approach to manage CSPs,
      with a short hospital stay, low postoperative pain, blood loss, and cost.

PMID- 25774121
TI  - A mixture of 86% of CO2, 10% of N2O, and 4% of oxygen permits laparoscopy under
      local anesthesia: a pilot study.
AB  - The aim of this study is to verify that 10 % of N2O in CO2 sufficiently reduces
      pain to permit laparoscopy under local anesthesia. In nine patients undergoing
      laparoscopy under local anesthesia for tubal sterilization, a mixture of 86 % of
      CO2, 10 % of N2O, and 4 % of oxygen (the Gas Mixture) was used for the
      pneumoperitoneum. For CO2, N2O, and for the Gas Mixture, the pain when blowing
      over the tongue tip and the pH changes of saline and Hartmann's solution were
      estimated. In all nine patients, discomfort was minimal and the intervention was
      well tolerated, similar to 100 % N2O. Tongue tip pain (n = 15), on VAS scale, was
      lower with 86 % CO2 + 10 % N2O + 4 % O2 (2.4 +/- 1.4, P = 0.005) and much lower
      with 100 % N2O (0.3 +/- 0.6, P < 0.0007) than with pure CO2 (3.6 +/- 1.7). The pH
      of saline (n = 5) decreased from 7.00 +/- 0.07 to 4.18 +/- 0.04 (P = 0.001), 6.98
      +/- 0.08 (NS), and 4.28 +/- 0.04 (P = 0.01) with 100 % CO2, 100 % N2O and the Gas
      Mixture, respectively. The pH of Hartmann's solution (n = 5) decreased similarly
      from 7.00 +/- 0.07 to 5.18 +/- 0.04 (P = 0.01), 7.02 +/- 0.19 (NS), and 5.3 +/-
      0.4 (P = 0.01), respectively. These data demonstrate that a mixture with 10 % of
      N2O and 4 % of O2 in CO2 permits laparoscopy under local anesthesia. This result
      cannot be explained by direct irritation estimated by tongue tip pain or by pH
      changes.

PMID- 25774122
TI  - Transcervical, intrauterine ultrasound-guided radiofrequency ablation of uterine
      fibroids with the VizAblate(r) System: three- and six-month endpoint results from
      the FAST-EU study.
AB  - This was a prospective, longitudinal, multicenter, single-arm controlled trial,
      using independent core laboratory validation of MRI results, to establish the
      effectiveness and confirm the safety of the VizAblate(r) System in the treatment
      of symptomatic uterine fibroids. The VizAblate System is a transcervical device
      that ablates fibroids with radiofrequency energy, guided by a built-in
      intrauterine ultrasound probe. Fifty consecutive women with symptomatic uterine
      fibroids received treatment with the VizAblate System. Patients had a minimum
      Menstrual Pictogram score of 120, no desire for fertility, and met additional
      inclusion and exclusion criteria. The VizAblate System was inserted
      transcervically and individual fibroids were ablated with radiofrequency energy.
      An integrated intrauterine ultrasound probe was used for fibroid imaging and
      targeting. Anesthesia was at the discretion of each investigator. The primary
      study endpoint was the percentage change in perfused fibroid volume, as assessed
      by contrast-enhanced MRI at 3 months. Secondary endpoints, reached at 6 months,
      included safety, percentage reductions in the Menstrual Pictogram (MP) score and
      the Symptom Severity Score (SSS) subscale of the Uterine Fibroid Symptom-Quality
      of Life questionnaire (UFS-QOL), along with the rate of surgical reintervention
      for abnormal uterine bleeding and the mean number of days to return to normal
      activity. Additional assessments included the Health-Related Quality of Life
      (HRQOL) subscale of the UFS-QOL, medical reintervention for abnormal uterine
      bleeding, and procedure times. Fifty patients were treated, representing 92
      fibroids. Perfused fibroid volumes were reduced at 3 months by an average of 68.8
      +/- 27.8 % (P < 0.0001; Wilcoxon signed-rank test). At 6 months, mean MP and SSS
      scores decreased by 60.8 +/- 38.2 and 59.7 +/- 30.4 %, respectively; the mean
      HRQOL score increased by 263 +/- 468 %. There were two serious adverse events
      (overnight admissions for abdominal pain and bradycardia, respectively) and no
      surgical reinterventions. These 6-month results suggest that the VizAblate System
      is safe and effective in providing relief of abnormal uterine bleeding associated
      with fibroids, with appropriate safety and a low reintervention rate.

PMID- 25774123
TI  - Lactate is always the end product of glycolysis.
AB  - Through much of the history of metabolism, lactate (La(-)) has been considered
      merely a dead-end waste product during periods of dysoxia. Congruently, the end
      product of glycolysis has been viewed dichotomously: pyruvate in the presence of
      adequate oxygenation, La(-) in the absence of adequate oxygenation. In contrast,
      given the near-equilibrium nature of the lactate dehydrogenase (LDH) reaction and
      that LDH has a much higher activity than the putative regulatory enzymes of the
      glycolytic and oxidative pathways, we contend that La(-) is always the end
      product of glycolysis. Cellular La(-) accumulation, as opposed to flux, is
      dependent on (1) the rate of glycolysis, (2) oxidative enzyme activity, (3)
      cellular O2 level, and (4) the net rate of La(-) transport into (influx) or out
      of (efflux) the cell. For intracellular metabolism, we reintroduce the Cytosol-to
      Mitochondria Lactate Shuttle. Our proposition, analogous to the phosphocreatine
      shuttle, purports that pyruvate, NAD(+), NADH, and La(-) are held uniformly near
      equilibrium throughout the cell cytosol due to the high activity of LDH. La(-) is
      always the end product of glycolysis and represents the primary diffusing species
      capable of spatially linking glycolysis to oxidative phosphorylation. 

PMID- 25774125
TI  - Human cerebral cortex Cajal-Retzius neuron: development, structure and function.
      A Golgi study.
AB  - The development, morphology and possible functional activity of the Cajal-Retzius
      cell of the developing human cerebral cortex are explored herein. The C-RC, of
      extracortical origin, is the essential neuron of the neocortex first lamina. It
      receives inputs from afferent fibers that reach the first lamina early in
      development. Although the origin and function of these original afferent fibers
      remain unknown, their target is the first lamina sole neuron: the C-RC. This
      neuron orchestrates the arrival, size and stratification of all pyramidal neurons
      (of ependymal origin) of the neocortex gray matter. Its axonic terminals spread
      radially and horizontally throughout the entirety of the first lamina
      establishing contacts with the dendritic terminals of all gray matter pyramidal
      cells regardless of size, location and/or eventual functional roles. While the
      neuron axonic terminals spread radially and horizontally throughout the first
      lamina, the neuronal' body undergoes progressive developmental dilution and
      locating any of them in the adult brain become quite difficult. The neuron bodies
      are probably retained in the older regions of the neocortex while their axonic
      collaterals will spread throughout its more recent ones and eventually will
      extend to great majority of the cortical surface. The neocortex first lamina
      evolution and composition and that of the C-RC are intertwined and mutually
      interdependent. It is not possible to understand the C-RC evolving morphology
      without understanding that of the first lamina. The first lamina composition and
      its structural and functional organizations obtained with different staining
      methods may be utterly different. These differences have added unnecessary
      confusion about its nature. The essential emptiness observed in hematoxylin and
      eosin preparations (most commonly used) contrast sharply with the concentration
      of dendrites (the cortex' largest) obtained using special (MAP-2) stain for
      dendrites. Only Golgi preparations demonstrate the numerous dendritic and axonic
      terminals that compose the first lamina basic structure. High power microscopic
      views of Golgi preparations demonstrate the intimate anatomical and functional
      interrelationships among dendritic and axonic terminals as well as synaptic
      contacts between them. The C-RC' essential morphology does not changes but it is
      progressively modified by the first lamina increase in thickness and in number of
      terminal dendrites and their subsequent maturation. This neuron variable
      morphologic appearance has been the source of controversy. Its morphology depends
      on the first lamina thickness that may be quite variable among different mammals.
      In rodents (most commonly used experimental mammal), the first lamina thickness,
      number and horizontal expansion of dendrites is but a fraction of those in
      humans. This differences are reflected in the C-RC' morphology among mammals
      (including humans) and should not be thought as representing new types of
      neurons. 

PMID- 25774124
TI  - Epigenetic mechanisms in neurological and neurodegenerative diseases.
AB  - The role of epigenetic mechanisms in the function and homeostasis of the central
      nervous system (CNS) and its regulation in diseases is one of the most
      interesting processes of contemporary neuroscience. In the last decade, a growing
      body of literature suggests that long-term changes in gene transcription
      associated with CNS's regulation and neurological disorders are mediated via
      modulation of chromatin structure. "Epigenetics", introduced for the first time
      by Waddington in the early 1940s, has been traditionally referred to a variety of
      mechanisms that allow heritable changes in gene expression even in the absence of
      DNA mutation. However, new definitions acknowledge that many of these mechanisms
      used to perpetuate epigenetic traits in dividing cells are used by neurons to
      control a variety of functions dependent on gene expression. Indeed, in the
      recent years these mechanisms have shown their importance in the maintenance of a
      healthy CNS. Moreover, environmental inputs that have shown effects in CNS
      diseases, such as nutrition, that can modulate the concentration of a variety of
      metabolites such as acetyl-coenzyme A (acetyl-coA), nicotinamide adenine
      dinucleotide (NAD(+)) and beta hydroxybutyrate (beta-HB), regulates some of these
      epigenetic modifications, linking in a precise way environment with gene
      expression. This manuscript will portray what is currently understood about the
      role of epigenetic mechanisms in the function and homeostasis of the CNS and
      their participation in a variety of neurological disorders. We will discuss how
      the machinery that controls these modifications plays an important role in
      processes involved in neurological disorders such as neurogenesis and cell
      growth. Moreover, we will discuss how environmental inputs modulate these
      modifications producing metabolic and physiological alterations that could exert
      beneficial effects on neurological diseases. Finally, we will highlight possible
      future directions in the field of epigenetics and neurological disorders. 

PMID- 25774126
TI  - A spatially collocated sound thrusts a flash into awareness.
AB  - To interact effectively with the environment the brain integrates signals from
      multiple senses. It is currently unclear to what extent spatial information can
      be integrated across different senses in the absence of awareness. Combining
      dynamic continuous flash suppression (CFS) and spatial audiovisual stimulation,
      the current study investigated whether a sound facilitates a concurrent visual
      flash to elude flash suppression and enter perceptual awareness depending on
      audiovisual spatial congruency. Our results demonstrate that a concurrent sound
      boosts unaware visual signals into perceptual awareness. Critically, this process
      depended on the spatial congruency of the auditory and visual signals pointing
      towards low level mechanisms of audiovisual integration. Moreover, the concurrent
      sound biased the reported location of the flash as a function of flash
      visibility. The spatial bias of sounds on reported flash location was strongest
      for flashes that were judged invisible. Our results suggest that multisensory
      integration is a critical mechanism that enables signals to enter conscious
      perception. 

PMID- 25774127
TI  - Very low birth weight piglets show improved cognitive performance in the spatial
      cognitive holeboard task.
AB  - Low birth weight (LBW) is common in humans and has been found to cause lasting
      cognitive and developmental deficits later in life. It is thought that the
      primary cause is intra-uterine growth restriction (IUGR) due to a shortage of
      oxygen and supply of nutrients to the fetus. Pigs appear to be a good model
      animal to investigate long-term cognitive effects of LBW, as LBW is common in
      commercially farmed breeds of pigs. Moreover, pigs are developmentally similar to
      humans and can be trained to perform complex tasks. In this study, we trained ten
      very low birth weight (vLBW) piglets and their ten normal birth weight (NBW)
      siblings in a spatial cognitive holeboard task in order to investigate long-term
      cognitive effects of LBW. In this task, four out of sixteen holes contain a
      hidden food reward, which allows measuring working memory (WM) (short-term
      memory) and reference memory (RM) (long-term memory) in parallel. Piglets were
      trained for 46-54 trials during the acquisition phase, followed by a 20-trial
      reversal phase in which a different set of four holes was baited. Both groups
      acquired the task and improved their performance over time. A mixed model
      repeated measures ANOVA revealed that vLBW piglets showed better RM performance
      than NBW piglets in both the acquisition and reversal phase. Additionally, WM
      scores in the vLBW were less disrupted than in the NBW animals when switched to
      the reversal phase. These findings are contrary to findings in humans. Moreover,
      vLBW pigs had lower hair cortisol concentrations (HCCs) than NBW pigs in flank
      hair at 12 weeks of age. These results could indicate that restricted intra
      uterine growth causes compensatory mechanisms to arise in early development that
      result in beneficial effects for vLBW piglets, increasing their low survival
      chances in early-life competition. 

PMID- 25774128
TI  - Altered food-cue processing in chronically ill and recovered women with anorexia
      nervosa.
AB  - Anorexia nervosa (AN) is a severe mental disorder characterized by food
      restriction and weight loss. This study aimed to test the model posed by Brooks
      et al. (2012a,b) that women suffering from chronic AN show decreased food-cue
      processing activity in brain regions associated with energy balance and food
      reward (bottom-up; BU) and increased activity in brain regions associated with
      cognitive control (top-down; TD) when compared with long-term recovered AN (REC)
      and healthy controls (HC). Three groups of women, 15 AN (mean illness duration
      7.8 +/- 4.1 years), 14 REC (mean duration of recovery 4.7 +/- 2.7 years) and 15
      HC viewed alternating blocks of food and non-food images preceded by a short
      instruction during functional magnetic resonance imaging (fMRI), after fasting
      overnight. Functional region of interests (fROIs) were defined in BU (e.g.,
      striatum, hippocampus, amygdala, hypothalamus, and cerebellum), TD (e.g., medial
      and lateral prefrontal cortex, and anterior cingulate), the insula, and visual
      processing areas (VPA). Food-cue processing activation was extracted from all
      fROIs and compared between the groups. In addition, functional connectivity
      between the fROIs was examined by modular partitioning of the correlation matrix
      of all fROIs. We could not confirm the hypothesis that BU areas are activated to
      a lesser extent in AN upon visual processing of food images. Among the BU areas
      the caudate showed higher activation in both patient groups compared to HC. In
      accordance with Brooks et al.'s model, we did find evidence for increased TD
      control in AN and REC. The functional connectivity analysis yielded two clusters
      in HC and REC, but three clusters in AN. In HC, fROIs across BU, TD, and VPA
      areas clustered; in AN, one cluster span across BU, TD, and insula; one across
      BU, TD, and VPA areas; and one was confined to the VPA network. In REC, BU, TD,
      and VPA or VPA and insula clustered. In conclusion, despite weight recovery,
      neural processing of food cues is also altered in recovered AN patients. 

PMID- 25774130
TI  - Imaging deductive reasoning and the new paradigm.
AB  - There has been a great expansion of research into human reasoning at all of
      Marr's explanatory levels. There is a tendency for this work to progress within a
      level largely ignoring the others which can lead to slippage between levels
      (Chater et al., 2003). It is argued that recent brain imaging research on
      deductive reasoning-implementational level-has largely ignored the new paradigm
      in reasoning-computational level (Over, 2009). Consequently, recent imaging
      results are reviewed with the focus on how they relate to the new paradigm. The
      imaging results are drawn primarily from a recent meta-analysis by Prado et al.
      (2011) but further imaging results are also reviewed where relevant. Three main
      observations are made. First, the main function of the core brain region
      identified is most likely elaborative, defeasible reasoning not deductive
      reasoning. Second, the subtraction methodology and the meta-analytic approach may
      remove all traces of content specific System 1 processes thought to underpin much
      human reasoning. Third, interpreting the function of the brain regions activated
      by a task depends on theories of the function that a task engages. When there are
      multiple interpretations of that function, interpreting what an active brain
      region is doing is not clear cut. It is concluded that there is a need to more
      tightly connect brain activation to function, which could be achieved using
      formalized computational level models and a parametric variation approach. 

PMID- 25774129
TI  - The neurobiology of emotion-cognition interactions: fundamental questions and
      strategies for future research.
AB  - Recent years have witnessed the emergence of powerful new tools for assaying the
      brain and a remarkable acceleration of research focused on the interplay of
      emotion and cognition. This work has begun to yield new insights into fundamental
      questions about the nature of the mind and important clues about the origins of
      mental illness. In particular, this research demonstrates that stress, anxiety,
      and other kinds of emotion can profoundly influence key elements of cognition,
      including selective attention, working memory, and cognitive control. Often, this
      influence persists beyond the duration of transient emotional challenges,
      partially reflecting the slower molecular dynamics of catecholamine and hormonal
      neurochemistry. In turn, circuits involved in attention, executive control, and
      working memory contribute to the regulation of emotion. The distinction between
      the 'emotional' and the 'cognitive' brain is fuzzy and context-dependent. Indeed,
      there is compelling evidence that brain territories and psychological processes
      commonly associated with cognition, such as the dorsolateral prefrontal cortex
      and working memory, play a central role in emotion. Furthermore, putatively
      emotional and cognitive regions influence one another via a complex web of
      connections in ways that jointly contribute to adaptive and maladaptive behavior.
      This work demonstrates that emotion and cognition are deeply interwoven in the
      fabric of the brain, suggesting that widely held beliefs about the key
      constituents of 'the emotional brain' and 'the cognitive brain' are fundamentally
      flawed. We conclude by outlining several strategies for enhancing future
      research. Developing a deeper understanding of the emotional-cognitive brain is
      important, not just for understanding the mind but also for elucidating the root
      causes of its disorders. 

PMID- 25774131
TI  - The influence of population size, noise strength and behavioral task on best
      encoded stimulus for neurons with unimodal or monotonic tuning curves.
AB  - Tuning curves and receptive fields are widely used to describe the selectivity of
      sensory neurons, but the relationship between firing rates and information is not
      always intuitive. Neither high firing rates nor high tuning curve gradients
      necessarily mean that stimuli at that part of the tuning curve are well
      represented by a neuron. Recent research has shown that trial-to-trial
      variability (noise) and population size can strongly affect which stimuli are
      most precisely represented by a neuron in the context of a population code (the
      best-encoded stimulus), and that different measures of information can give
      conflicting indications. Specifically, the Fisher information is greatest where
      the tuning curve gradient is greatest, such as on the flanks of peaked tuning
      curves, but the stimulus-specific information (SSI) is greatest at the tuning
      curve peak for small populations with high trial-to-trial variability. Previous
      research in this area has focussed upon unimodal (peaked) tuning curves, and in
      this article we extend these analyses to monotonic tuning curves. In addition, we
      examine how stimulus spacing in forced choice tasks affects the best-encoded
      stimulus. Our results show that, regardless of the tuning curve, Fisher
      information correctly predicts the best-encoded stimulus for large populations
      and where the stimuli are closely spaced in forced choice tasks. In smaller
      populations with high variability, or in forced choice tasks with widely-spaced
      choices, the best-encoded stimulus falls at the peak of unimodal tuning curves,
      but is more variable for monotonic tuning curves. Task, population size and
      variability all need to be considered when assessing which stimuli a neuron
      represents, but the best-encoded stimulus can be estimated on a case-by case
      basis using commonly available computing facilities. 

PMID- 25774132
TI  - Dendritic distributions of I h channels in experimentally-derived multi
      compartment models of oriens-lacunosum/moleculare (O-LM) hippocampal
      interneurons.
AB  - The O-LM cell type mediates feedback inhibition onto hippocampal pyramidal cells
      and gates information flow in the CA1. Its functions depend on the presence of
      voltage-gated channels (VGCs), which affect its integrative properties and
      response to synaptic input. Given the challenges associated with determining
      densities and distributions of VGCs on interneuron dendrites, we take advantage
      of computational modeling to consider different possibilities. In this work, we
      focus on hyperpolarization-activated channels (h-channels) in O-LM cells. While h
      channels are known to be present in O-LM cells, it is unknown whether they are
      present on their dendrites. In previous work, we used ensemble modeling
      techniques with experimental data to obtain insights into potentially important
      conductance balances. We found that the best O-LM models that included uniformly
      distributed h-channels in the dendrites could not fully capture the "sag"
      response. This led us to examine activation kinetics and non-uniform
      distributions of h-channels in the present work. In tuning our models, we found
      that different kinetics and non-uniform distributions could better reproduce
      experimental O-LM cell responses. In contrast to CA1 pyramidal cells where higher
      conductance densities of h-channels occur in more distal dendrites, decreasing
      conductance densities of h-channels away from the soma were observed in O-LM
      models. Via an illustrative scenario, we showed that having dendritic h-channels
      clearly speeds up back-propagating action potentials in O-LM cells, unlike when h
      channels are present only in the soma. Although the present results were
      morphology-dependent, our work shows that it should be possible to determine the
      distributions and characteristics of O-LM cells with recordings and morphologies
      from the same cell. We hypothesize that h-channels are distributed in O-LM cell
      dendrites and endow them with particular synaptic integration properties that
      shape information flow in hippocampus. 

PMID- 25774134
TI  - Application of morbid animal model in drug safety evaluation of traditional
      Chinese medicine.
AB  - During thousands of years of clinical validation and practice, the efficacy and
      safety of traditional Chinese medicine (TCM) have been widely recognized in the
      prevention and treatment for various diseases. However, further toxicology
      research of TCM new drugs is still necessary. 

PMID- 25774133
TI  - Circadian clock disruption in neurodegenerative diseases: cause and effect?
AB  - Disturbance of the circadian system, manifested as disrupted daily rhythms of
      physiologic parameters such as sleep, activity, and hormone secretion, has long
      been observed as a symptom of several neurodegenerative diseases, including
      Alzheimer disease. Circadian abnormalities have generally been considered
      consequences of the neurodegeneration. Recent evidence suggests, however, that
      circadian disruption might actually contribute to the neurodegenerative process,
      and thus might be a modifiable cause of neural injury. Herein we will review the
      evidence implicating circadian rhythms disturbances and clock gene dysfunction in
      neurodegeneration, with an emphasis on future research directions and potential
      therapeutic implications for neurodegenerative diseases. 

PMID- 25774135
TI  - High fat feeding affects the number of GPR120 cells and enteroendocrine cells in
      the mouse stomach.
AB  - Long-term intake of dietary fat is supposed to be associated with adaptive
      reactions of the organism and it is assumptive that this is particularly true for
      fat responsive epithelial cells in the mucosa of the gastrointestinal tract.
      Recent studies suggest that epithelial cells expressing the receptor for medium
      and long chain fatty acids, GPR120 (FFAR4), may operate as fat sensors. Changes
      in expression level and/or cell density are supposed to be accompanied with a
      consumption of high fat (HF) diet. To assess whether feeding a HF diet might
      impact on the expression of fatty acid receptors or the number of lipid sensing
      cells as well as enteroendocrine cell populations, gastric tissue samples of non
      obese and obese mice were compared using a real time PCR and immunohistochemical
      approach. In this study, we have identified GPR120 cells in the corpus region of
      the mouse stomach which appeared to be brush cells. Monitoring the effect of HF
      diet on the expression of GPR120 revealed that after 3 weeks and 6 months the
      level of mRNA for GPR120 in the tissue was significantly increased which
      coincided with and probably reflected a significant increase in the number of
      GPR120 positive cells in the corpus region; in contrast, within the antrum
      region, the number of GPR120 cells decreased. Furthermore, dietary fat intake
      also led to changes in the number of enteroendocrine cells producing either
      ghrelin or gastrin. After 3 weeks and even more pronounced after 6 months the
      number of ghrelin cells and gastrin cells was significantly increased. These
      results imply that a HF diet leads to significant changes in the cellular
      repertoire of the stomach mucosa. Whether these changes are a consequence of the
      direct exposure to HF in the luminal content or a physiological response to the
      high level of fat in the body remains elusive. 

PMID- 25774136
TI  - Selectivity of odorant-binding proteins from the southern house mosquito tested
      against physiologically relevant ligands.
AB  - As opposed to humans, insects rely heavily on an acute olfactory system for
      survival and reproduction. Two major types of olfactory proteins, namely, odorant
      binding proteins (OBPs) and odorant receptors (ORs), may contribute to the
      selectivity and sensitivity of the insects' olfactory system. Here, we aimed at
      addressing the question whether OBPs highly enriched in the antennae of the
      southern house mosquito, Culex quinquefasciatus, contribute at least in part to
      the selective reception of physiologically relevant compounds. Using a
      fluorescence reporter and a panel of 34 compounds, including oviposition
      attractants, human-derived attractants, and repellents, we measured binding
      affinities of CquiOBP1, CquiOBP2, and CquiOBP5. Based on dissociation constants,
      we surmised that CquiOBP2 is a carrier for the oviposition attractant skatole,
      whereas CquiOBP1 and CquiOBP5 might transport the oviposition pheromone MOP, a
      human-derived attractant nonanal, and the insect repellent picardin. Binding of
      these three ligands to CquiOBP1 was further analyzed by examining the influence
      of pH on apparent affinity as well as by docking these three ligands into
      CquiOBP1. Our findings suggest that CquiOBP1 might discriminate MOP from
      nonanal/picaridin on the basis of the midpoint transition of a pH-dependence
      conformational change, and that MOP is better accommodated in the binding cavity
      than the other two ligands. These findings, along with previous experimental
      evidence suggesting that CquiOBP1 does not detect nonanal in vivo, suggest that
      OBP selectivity may not be clearly manifested in their dissociation constants. 

PMID- 25774137
TI  - Neurobiological foundations of neurologic music therapy: rhythmic entrainment and
      the motor system.
AB  - Entrainment is defined by a temporal locking process in which one system's motion
      or signal frequency entrains the frequency of another system. This process is a
      universal phenomenon that can be observed in physical (e.g., pendulum clocks) and
      biological systems (e.g., fire flies). However, entrainment can also be observed
      between human sensory and motor systems. The function of rhythmic entrainment in
      rehabilitative training and learning was established for the first time by Thaut
      and colleagues in several research studies in the early 1990s. It was shown that
      the inherent periodicity of auditory rhythmic patterns could entrain movement
      patterns in patients with movement disorders (see for a review: Thaut et al.,
      1999). Physiological, kinematic, and behavioral movement analysis showed very
      quickly that entrainment cues not only changed the timing of movement but also
      improved spatial and force parameters. Mathematical models have shown that
      anticipatory rhythmic templates as critical time constraints can result in the
      complete specification of the dynamics of a movement over the entire movement
      cycle, thereby optimizing motor planning and execution. Furthermore, temporal
      rhythmic entrainment has been successfully extended into applications in
      cognitive rehabilitation and speech and language rehabilitation, and thus become
      one of the major neurological mechanisms linking music and rhythm to brain
      rehabilitation. These findings provided a scientific basis for the development of
      neurologic music therapy. 

PMID- 25774138
TI  - Body ownership and experiential ownership in the self-touching illusion.
AB  - We investigate two issues about the subjective experience of one's body: first,
      is the experience of owning a full-body fundamentally different from the
      experience of owning a body-part?Second, when I experience a bodily sensation,
      does it guarantee that I cannot be wrong about whether it is me who feels it? To
      address these issues, we conducted a series of experiments that combined the
      rubber hand illusion (RHI) and the "body swap illusion." The subject wore a head
      mounted display (HMD) connected with a stereo camera set on the experimenter's
      head. Sitting face to face, they used their right hand holding a paintbrush to
      brush each other's left hand. Through the HMD, the subject adopted the
      experimenter's first-person perspective (1PP) as if it was his/her own 1PP: the
      subject watched either the experimenter's hand from the adopted 1PP, and/or the
      subject's own hand from the adopted third-person perspective (3PP) in the
      opposite direction (180 degrees ), or the subject's full body from the adopted
      3PP (180 degrees , with or without face). The synchronous full-body conditions
      generate a "self-touching illusion": many participants felt that "I was brushing
      my own hand!" We found that (1) the sense of body-part ownership and the sense of
      full-body ownership are not fundamentally different from each other; and (2) our
      data present a strong case against the mainstream philosophical view called the
      immunity principle (IEM). We argue that it is possible for misrepresentation to
      occur in the subject's sense of "experiential ownership" (the sense that I am the
      one who is having this bodily experience). We discuss these findings and conclude
      that not only the sense of body ownership but also the sense of experiential
      ownership call for further interdisciplinary studies. 

PMID- 25774139
TI  - Embodied intersubjective engagement in mother-infant tactile communication: a
      cross-cultural study of Japanese and Scottish mother-infant behaviors during
      infant pick-up.
AB  - This study examines the early development of cultural differences in a simple,
      embodied, and intersubjective engagement between mothers putting down, picking
      up, and carrying their infants between Japan and Scotland. Eleven Japanese and
      ten Scottish mothers with their 6- and then 9-month-old infants participated.
      Video and motion analyses were employed to measure motor patterns of the mothers'
      approach to their infants, as well as their infants' collaborative responses
      during put-down, pick-up, and carry phases. Japanese and Scottish mothers
      approached their infants with different styles and their infants responded
      differently to the short duration of separation during the trial. A greeting-like
      behavior of the arms and hands was prevalent in the Scottish mothers' approach,
      but not in the Japanese mothers' approach. Japanese mothers typically kneeled
      before making the final reach to pick-up their children, giving a closer,
      apparently gentler final approach of the torso than Scottish mothers, who bent at
      the waist with larger movements of the torso. Measures of the gap closure between
      the mothers' hands to their infants' heads revealed variably longer duration and
      distance gap closures with greater velocity by the Scottish mothers than by the
      Japanese mothers. Further, the sequence of Japanese mothers' body actions on
      approach, contact, pick-up, and hold was more coordinated at 6 months than at 9
      months. Scottish mothers were generally more variable on approach. Measures of
      infant participation and expressivity indicate more active participation in the
      negotiation during the separation and pick-up phases by Scottish infants. Thus,
      this paper demonstrates a culturally different onset of development of joint
      attention in pick-up. These differences reflect cultures of everyday interaction.

PMID- 25774140
TI  - Reassessing intertemporal choice: human decision-making is more optimal in a
      foraging task than in a self-control task.
AB  - Many contemporary concerns (e.g., addiction, failure to save) can be viewed as
      intertemporal choice problems in which the consequences of choices are realized
      at different times. In some laboratory paradigms used to study intertemporal
      choice, non-human animals demonstrate a preference for immediacy (impulsive
      choice) that results in failures to maximize the amount of reward received. There
      is evidence, however, suggesting that such non-optimal impulsive choice may be
      due to a mismatch between the standard presentation of options in the laboratory
      (e.g., a "larger-later" and a "smaller-sooner" option) and the way that options
      occur in natural settings (e.g., foraging). We present evidence that human
      impulsive choice is similarly affected: in two experiments, decisions were more
      optimal when options were presented in a format sharing features with the
      evolutionarily important problem of foraging compared to when options were
      presented in the standard format. These findings suggest a more nuanced view of
      intertemporal choice and support the adoption of ideas from foraging theory into
      the study of human decision making. 

PMID- 25774141
TI  - Group learning capacity: the roles of open-mindedness and shared vision.
AB  - Open-mindedness (OPM) is a construct that is considered a key foundational aspect
      of learning in individuals, groups and organizations. Also known as critical
      inquiry or reflection, OPM is believed to increase learning through examination
      of prior beliefs, decisions and mistakes, and also through openness to new ideas.
      Renowned theorists including Dewey and Argyris have emphasized the relationship
      between OPM and learning, yet little quantitative research has tested it or
      examined moderators of the linkage. The setting for the current study is that of
      endowment investment committees at U.S. universities and colleges who need to
      make knowledgeable and well-reasoned decisions about the composition of
      investment portfolios. Findings indicate that OPM has a positive, significant
      effect on group learning capacity (LCAP) and also that shared vision, which
      represents the group's collective purpose and direction, moderates that
      relationship. The literature review and discussion offer insights about how OPM
      is related to the research on group conflict, and how shared vision (SHV) differs
      from concepts such as interpersonal cohesiveness and conformity that have been
      associated with groupthink. A review of relevant research from the fields of
      organizational learning, group dynamics, and absorptive capacity provides context
      for the development of the hypotheses and the discussion of findings. 

PMID- 25774142
TI  - Modality of fear cues affects acoustic startle potentiation but not heart-rate
      response in patients with dental phobia.
AB  - The acoustic startle response (SR) has consistently been shown to be enhanced by
      fear-arousing cross-modal background stimuli in phobics. Intra-modal fear
      potentiation of acoustic SR was rarely investigated and generated inconsistent
      results. The present study compared the acoustic SR to phobia-related sounds with
      that to phobia-related pictures in 104 dental phobic patients and 22 controls.
      Acoustic background stimuli were dental treatment noises and birdsong and visual
      stimuli were dental treatment and neutral control pictures. Background stimuli
      were presented for 4 s, randomly followed by the administration of the startle
      stimulus. In addition to SR, heart-rate (HR) was recorded throughout the trials.
      Irrespective of their content, background pictures elicited greater SR than
      noises in both groups with a trend for phobic participants to show startle
      potentiation to phobia-related pictures but not noises. Unlike controls, phobics
      showed HR acceleration to both dental pictures and noises. HR acceleration of the
      phobia group was significantly positively correlated with SR in the noise
      condition only. The acoustic SR to phobia-related noises is likely to be
      inhibited by prolonged sensorimotor gating. 

PMID- 25774144
TI  - Perception of gait patterns that deviate from normal and symmetric biped
      locomotion.
AB  - This study examines the range of gait patterns that are perceived as healthy and
      human-like with the goal of understanding how much asymmetry is allowable in a
      gait pattern before other people start to notice a gait impairment. Specifically,
      this study explores if certain abnormal walking patterns can be dismissed as
      unimpaired or not uncanny. Altering gait biomechanics is generally done in the
      fields of prosthetics and rehabilitation, however the perception of gait is often
      neglected. Although a certain gait can be functional, it may not be considered as
      normal by observers. On the other hand, an abnormally perceived gait may be more
      practical or necessary in some situations, such as limping after an injury or
      stroke and when wearing a prosthesis. This research will help to find the balance
      between the form and function of gait. Gait patterns are synthetically created
      using a passive dynamic walker (PDW) model that allows gait patterns to be
      systematically changed without the confounding influence from human sensorimotor
      feedback during walking. This standardized method allows the perception of
      specific changes in gait to be studied. The PDW model was used to produce walking
      patterns that showed a degree of abnormality in gait cadence, knee height, step
      length, and swing time created by changing the foot roll-over-shape, knee
      damping, knee location, and leg masses. The gait patterns were shown to
      participants who rated them according to separate scales of impairment and
      uncanniness. The results indicate that some pathological and asymmetric gait
      patterns are perceived as unimpaired and normal. Step time and step length
      asymmetries less than 5%, small knee location differences, and gait cadence
      changes of 25% do not result in a change in perception. The results also show
      that the parameters of a pathologically or uncanny perceived gait can be
      beneficially altered by increasing other independent parameters, in some sense
      masking the initial pathology. 

PMID- 25774143
TI  - Future challenges for vection research: definitions, functional significance,
      measures, and neural bases.
AB  - This paper discusses four major challenges facing modern vection research.
      Challenge 1 (Defining Vection) outlines the different ways that vection has been
      defined in the literature and discusses their theoretical and experimental
      ramifications. The term vection is most often used to refer to visual illusions
      of self-motion induced in stationary observers (by moving, or simulating the
      motion of, the surrounding environment). However, vection is increasingly being
      used to also refer to non-visual illusions of self-motion, visually mediated self
      motion perceptions, and even general subjective experiences (i.e., "feelings") of
      self-motion. The common thread in all of these definitions is the conscious
      subjective experience of self-motion. Thus, Challenge 2 (Significance of Vection)
      tackles the crucial issue of whether such conscious experiences actually serve
      functional roles during self-motion (e.g., in terms of controlling or guiding the
      self-motion). After more than 100 years of vection research there has been
      surprisingly little investigation into its functional significance. Challenge 3
      (Vection Measures) discusses the difficulties with existing subjective self
      report measures of vection (particularly in the context of contemporary
      research), and proposes several more objective measures of vection based on
      recent empirical findings. Finally, Challenge 4 (Neural Basis) reviews the recent
      neuroimaging literature examining the neural basis of vection and discusses the
      hurdles still facing these investigations. 

PMID- 25774145
TI  - The mirror illusion: does proprioceptive drift go hand in hand with sense of
      agency?
AB  - Vection can be regarded as the illusion of "whole-body" position perception. In
      contrast, the mirror illusion is that of "body-part" position perception. When
      participants viewed their left hands in a mirror positioned along the midsaggital
      axis while moving both hands synchronously, they hardly noticed the spatial
      offset between the hand in the mirror and the obscured real right hand. This
      illusion encompasses two phenomena: proprioceptive drift and sense of agency.
      Proprioceptive drift represented a perceptual change in the position of the
      obscured hand relative to that of the hand in the mirror. Sense of agency
      referred to the participants' subjective sense of controlling body image as they
      would their own bodies. We examined the spatial offset between these two
      phenomena. Participants responded to a two-alternative forced choice (2AFC)
      question regarding the subjective position of their right hands and
      questionnaires regarding sense of agency at various positions of the right hand.
      We analyzed the 2AFC data using a support vector machine and compared its
      classification result and the questionnaire results. Our data analysis suggested
      that the two phenomena were observed in concentric space, but the estimated range
      of the proprioceptive drift was slightly narrower than the range of agency.
      Although this outcome can be attributed to differences in measurement or
      analysis, to our knowledge, this is the first report to suggest that
      proprioceptive drift and sense of agency are concentric and almost overlap. 

PMID- 25774146
TI  - Bringing the well being and patient safety research agenda together: why healthy
      HPs equal safe patients.

PMID- 25774147
TI  - Primary process emotion, identity, and culture: cultural identification's roots
      in basic motivation.

PMID- 25774148
TI  - Functional or psychogenic movement disorders: an endless enigmatic tale.

PMID- 25774150
TI  - Analysis of methane-producing and metabolizing archaeal and bacterial communities
      in sediments of the northern South China Sea and coastal Mai Po Nature Reserve
      revealed by PCR amplification of mcrA and pmoA genes.
AB  - Communities of methanogens, anaerobic methanotrophic archaea and aerobic
      methanotrophic bacteria (MOB) were compared by profiling polymerase chain
      reaction (PCR)-amplified products of mcrA and pmoA genes encoded by methyl
      coenzyme M reductase alpha subunit and particulate methane monooxygenase alpha
      subunit, respectively, in sediments of northern South China Sea (nSCS) and Mai Po
      mangrove wetland. Community structures representing by mcrA gene based on 12
      clone libraries from nSCS showed separate clusters indicating niche specificity,
      while, Methanomicrobiales, Methanosarcinales clades 1,2, and
      Methanomassiliicoccus-like groups of methanogens were the most abundant groups in
      nSCS sediment samples. Novel clusters specific to the SCS were identified and the
      phylogeny of mcrA gene-harboring archaea was updated. Quantitative polymerase
      chain reaction was used to detect mcrA gene abundance in all samples: similar
      abundance of mcrA gene in the surface layers of mangrove (3.4~3.9 * 10(6) copies
      per gram dry weight) and of intertidal mudflat (5.5~5.8 * 10(6) copies per gram
      dry weight) was observed, but higher abundance (6.9 * 10(6) to 1.02 * 10(8)
      copies per gram dry weight) was found in subsurface samples of both sediment
      types. Aerobic MOB were more abundant in surface layers (6.7~11.1 * 10(5) copies
      per gram dry weight) than the subsurface layers (1.2~5.9 * 10(5) copies per gram
      dry weight) based on pmoA gene. Mangrove surface layers harbored more abundant
      pmoA gene than intertidal mudflat, but less pmoA genes in the subsurface layers.
      Meanwhile, it is also noted that in surface layers of all samples, more pmoA gene
      copies were detected than the subsurface layers. Reedbed rhizosphere exhibited
      the highest gene abundance of mcrA gene (8.51 * 10(8) copies per gram dry weight)
      and pmoA gene (1.56 * 10(7) copies per gram dry weight). This study investigated
      the prokaryotic communities responsible for methane cycling in both marine and
      coastal wetland ecosystems, showing the distribution characteristics of mcrA gene
      harboring communities in nSCS and stratification of mcrA and pmoA gene diversity
      and abundance in the Mai Po Nature Reserve. 

PMID- 25774149
TI  - IGF-Binding Protein 2 - Oncogene or Tumor Suppressor?
AB  - The role of insulin-like growth factor binding protein 2 (IGFBP2) in cancer is
      unclear. In general, IGFBP2 is considered to be oncogenic and its expression is
      often observed to be elevated in cancer. However, there are a number of
      conflicting reports in vitro and in vivo where IGFBP2 acts in a tumor suppressor
      manner. In this mini-review, we discuss the factors influencing the variation in
      IGFBP2 expression in cancer and our interpretation of these findings. 

PMID- 25774151
TI  - Archaeal membrane-associated proteases: insights on Haloferax volcanii and other
      haloarchaea.
AB  - The function of membrane proteases range from general house-keeping to regulation
      of cellular processes. Although the biological role of these enzymes in archaea
      is poorly understood, some of them are implicated in the biogenesis of the
      archaeal cell envelope and surface structures. The membrane-bound ATP-dependent
      Lon protease is essential for cell viability and affects membrane carotenoid
      content in Haloferax volcanii. At least two different proteases are needed in
      this archaeon to accomplish the posttranslational modifications of the S-layer
      glycoprotein. The rhomboid protease RhoII is involved in the N-glycosylation of
      the S-layer protein with a sulfoquinovose-containing oligosaccharide while
      archaeosortase ArtA mediates the proteolytic processing coupled-lipid
      modification of this glycoprotein facilitating its attachment to the archaeal
      cell surface. Interestingly, two different signal peptidase I homologs exist in
      H. volcanii, Sec11a and Sec11b, which likely play distinct physiological roles.
      Type IV prepilin peptidase PibD processes flagellin/pilin precursors, being
      essential for the biogenesis and function of the archaellum and other cell
      surface structures in H. volcanii. 

PMID- 25774152
TI  - In vitro adhesion properties of Shiga toxin-producing Escherichia coli isolated
      from cattle, food, and humans.
AB  - Shiga toxin-producing Escherichia coli (STEC) are able to cause serious illnesses
      ranging from diarrhea to hemorrhagic colitis and hemolytic-uremic syndrome (HUS).
      These bacteria colonize the digestive tract of humans and produce Shiga-toxins,
      which are considered to be essential for virulence and are crucial in lethal
      infection. Colon colonization is supposed to be a determinant step in the
      development of the infection, but the virulence traits that mediate this step are
      unclear. We analyzed the ability of 256 STEC strains belonging to seropathotype A
      (the most virulent O157:H7 serotype) to seropathotype E (not involved in human
      disease) to adhere to HEp-2, HCT-8, and T84 cell lines. Of the 256 STEC tested
      most (82%) were non-adherent in our assays. The adhesion levels were globally low
      and were not related to pathogenicity, although the highest levels were
      associated to O26:H11 and O103:H2 strains of seropathotype B (associated with HUS
      but less commonly than serotype O157:H7), possessing both the eae and toxB genes.

PMID- 25774153
TI  - Isolation of diverse members of the Aquificales from geothermal springs in
      Tengchong, China.
AB  - The order Aquificales (phylum Aquificae) consists of thermophilic and
      hyperthermophilic bacteria that are prominent in many geothermal systems,
      including those in Tengchong, Yunnan Province, China. However, Aquificales have
      not previously been isolated from Tengchong. We isolated five strains of
      Aquificales from diverse springs (temperature 45.2-83.3 degrees C and pH 2.6-9.1)
      in the Rehai Geothermal Field from sites in which Aquificales were abundant.
      Phylogenetic analysis showed that four of the strains belong to the genera
      Hydrogenobacter, Hydrogenobaculum, and Sulfurihydrogenibium, including strains
      distant enough to likely justify new species of Hydrogenobacter and
      Hydrogenobaculum. The additional strain may represent a new genus in the
      Hydrogenothermaceae. All strains were capable of aerobic respiration under
      microaerophilic conditions; however, they had variable capacity for
      chemolithotrophic oxidation of hydrogen and sulfur compounds and nitrate
      reduction. 

PMID- 25774154
TI  - Stoichiometric flexibility in diverse aquatic heterotrophic bacteria is coupled
      to differences in cellular phosphorus quotas.
AB  - It is frequently presumed that heterotrophic bacteria from aquatic environments
      have low carbon (C) content, high phosphorus (P) content, and maintain
      homeostasis at low C:P in their biomass. Dissolved and particulate organic matter
      from primary producers in terrestrial and aquatic environments typically has high
      C:P ratios, suggesting that heterotrophic bacteria consuming this resource
      experience stoichiometric imbalance in C and P. The strength of elemental
      homeostasis is important for understanding how heterotrophic bacteria couple C
      and P cycles in response to environmental change, yet these generalizations are
      based upon data from only a few species that might not represent the physiology
      of bacteria in freshwaters. However, recent research has indicated that some
      strains of bacteria isolated from freshwaters have flexible C:P stoichiometry and
      can acclimate to changes in resource C:P. Although it is apparent that strains
      differ in their biomass C:P and flexibility, the basis for these characteristics
      has not been explained. We evaluated biomass C:P homeostasis in 24 strains of
      bacteria isolated from temperate lakes using a uniform relative growth rate in
      chemostats. Overall, the strains exhibited a range of homeostatic regulation from
      strong homeostasis to highly flexible biomass stoichiometry, but strains that
      were isolated using P-rich media formulations were more homeostatic than strains
      isolated using P-poor media. Strains exhibiting homeostatic biomass C:P had high
      cellular C and P content and showed little morphological change between C and P
      limitation. In contrast, stoichiometrically flexible strains had low P quotas and
      increased their C quotas and cell size under P limitation. Because stoichiometric
      flexibility is closely coupled to absolute P content in bacteria, anthropogenic
      inputs of P could lead to prevalence of more homeostatic bacteria, reducing the
      ability of natural assemblages to buffer changes in the availability of P and
      organic C. 

PMID- 25774155
TI  - Targeting zinc homeostasis to combat Aspergillus fumigatus infections.
AB  - Aspergillus fumigatus is able to invade and grow in the lungs of immunosuppressed
      individuals and causes invasive pulmonary aspergillosis. The concentration of
      free zinc in living tissues is much lower than that required for optimal fungal
      growth in vitro because most of it is tightly bound to proteins. To obtain
      efficiently zinc from a living host A. fumigatus uses the zinc transporters ZrfA,
      ZrfB, and ZrfC. The ZafA transcriptional regulator induces the expression of all
      these transporters and is essential for virulence. Thus, ZafA could be targeted
      therapeutically to inhibit fungal growth. The ZrfC transporter plays the major
      role in zinc acquisition from the host whereas ZrfA and ZrfB rather have a
      supplementary role to that of ZrfC. In addition, only ZrfC enables A. fumigatus
      to overcome the inhibitory effect of calprotectin, which is an antimicrobial
      Zn/Mn-chelating protein synthesized and released by neutrophils within the fungal
      abscesses of immunosuppressed non-leucopenic animals. Hence, fungal survival in
      these animals would be undermined upon blocking therapeutically the function of
      ZrfC. Therefore, both ZafA and ZrfC have emerged as promising targets for the
      discovery of new antifungals to treat Aspergillus infections. 

PMID- 25774156
TI  - Colonization of plant substrates at hydrothermal vents and cold seeps in the
      northeast Atlantic and Mediterranean and occurrence of symbiont-related bacteria.
AB  - Reducing conditions with elevated sulfide and methane concentrations in
      ecosystems such as hydrothermal vents, cold seeps or organic falls, are suitable
      for chemosynthetic primary production. Understanding processes driving bacterial
      diversity, colonization and dispersal is of prime importance for deep-sea
      microbial ecology. This study provides a detailed characterization of bacterial
      assemblages colonizing plant-derived substrates using a standardized approach
      over a geographic area spanning the North-East Atlantic and Mediterranean. Wood
      and alfalfa substrates in colonization devices were deployed for different
      periods at 8 deep-sea chemosynthesis-based sites in four distinct geographic
      areas. Pyrosequencing of a fragment of the 16S rRNA-encoding gene was used to
      describe bacterial communities. Colonization occurred within the first 14 days.
      The diversity was higher in samples deployed for more than 289 days. After 289
      days, no relation was observed between community richness and deployment
      duration, suggesting that diversity may have reached saturation sometime in
      between. Communities in long-term deployments were different, and their
      composition was mainly influenced by the geographical location where devices were
      deployed. Numerous sequences related to horizontally-transmitted chemosynthetic
      symbionts of metazoans were identified. Their potential status as free-living
      forms of these symbionts was evaluated based on sequence similarity with
      demonstrated symbionts. Results suggest that some free-living forms of metazoan
      symbionts or their close relatives, such as Epsilonproteobacteria associated with
      the shrimp Rimicaris exoculata, are efficient colonizers of plant substrates at
      vents and seeps. 

PMID- 25774157
TI  - A Meta-Analysis of Experimental Studies of Attenuated Schistosoma mansoni
      Vaccines in the Mouse Model.
AB  - Schistosomiasis is a water-borne, parasitic disease of major public health
      importance. There has been considerable effort for several decades toward the
      development of a vaccine against the disease. Numerous mouse experimental studies
      using attenuated Schistosoma mansoni parasites for vaccination have been
      published since 1960s. However, to date, there has been no systematic review or
      meta-analysis of these data. The aim of this study is to identify measurable
      experimental conditions that affect the level of protection against re-infection
      with S. mansoni in mice vaccinated with radiation attenuated cercariae. Following
      a systematic review, a total of 755 observations were extracted from 105 articles
      (published 1963-2007) meeting the searching criteria. Random effects meta
      regression models were used to identify the influential predictors. Three
      predictors were found to have statistically significant effects on the level of
      protection from vaccination: increasing numbers of immunizing parasites had a
      positive effect on fraction of protection whereas increasing radiation dose and
      time to challenge infection had negative effects. Models showed that the
      irradiated cercariae vaccine has the potential to achieve protection as high as
      78% with a single dose vaccination. This declines slowly over time but remains
      high for at least 8 months after the last immunization. These findings provide
      insights into the optimal delivery of attenuated parasite vaccination and into
      the nature and development of protective vaccine induced immunity against
      schistosomiasis, which may inform the formulation of human vaccines and the
      predicted duration of protection and thus frequency of booster vaccines. 

PMID- 25774158
TI  - "Any Condomless Anal Intercourse" is No Longer an Accurate Measure of HIV Sexual
      risk Behavior in Gay and Other Men Who have Sex with Men.
AB  - BACKGROUND: Condomless anal intercourse (CLAI) has long been recognized as the
      primary mode of sexual transmission of HIV in gay and other men who have sex with
      men (MSM). A variety of measures of CLAI have been commonly used in behavioral
      surveillance for HIV risk and to forecast trends in HIV infection. However, gay
      and other MSM's sexual practices changed as the understanding of disease and
      treatment options advance. In the present paper, we argue that summary measures
      such as "any CLAI" do not accurately measure HIV sexual risk behavior. METHODS:
      Participants were 1,427 HIV-negative men from the Health in Men cohort study run
      from 2001 to 2007 in Sydney, Australia, with six-monthly interviews. At each
      interview, detailed quantitative data on the number of episodes of insertive and
      receptive CLAI in the last 6 months were collected, separated by partner type
      (regular vs. casual) and partners' HIV status (negative, positive, and HIV status
      unknown). RESULTS: A total of 228,064 episodes of CLAI were reported during the
      study period with a mean of 44 episodes per year per participant (median: 14).
      The great majority of CLAI episodes were with a regular partner (92.6%), most of
      them with HIV-negative regular partners (84.8%). Participants were more likely to
      engage in insertive CLAI with casual than with regular partners (66.7 vs. 55.3%
      of all acts of CLAI with each partner type, p < 0.001). Men were more likely to
      report CLAI in the receptive position with HIV-negative and HIV status unknown
      partners than with HIV-positive partners (p < 0.001 for both regular and casual
      partners). CONCLUSION: Gay and other MSM engaging in CLAI demonstrate clear
      patterns of HIV risk reduction behavior. As HIV prevention enters the era of
      antiretroviral-based biomedical approach, using all forms of CLAI
      indiscriminately as a measure of HIV behavioral risk is not helpful in
      understanding the current drivers of HIV transmission in the community.

PMID- 25774159
TI  - Overexpression of a peach CBF gene in apple: a model for understanding the
      integration of growth, dormancy, and cold hardiness in woody plants.
AB  - The timing of cold acclimation and deacclimation, dormancy, and budbreak play an
      integral role in the life cycle of woody plants. The molecular events that
      regulate these parameters have been the subject of much study, however, in most
      studies these events have been investigated independently of each other. Ectopic
      expression of a peach CBF (PpCBF1) in apple increases the level of both non
      acclimated and acclimated freezing tolerance relative to the non-transformed
      control, and also inhibits growth, induces early bud set and leaf senescence, and
      delays bud break in the spring. The current study examined differences in the
      seasonal expression of genes (CBF, DAM, RGL, and EBB) that have been reported to
      be associated with freezing tolerance, dormancy, growth, and bud break,
      respectively, in the PpCBF1 T166 transgenic apple line and the non-transformed
      M.26 control. Results indicated that expression of several of these key genes,
      including MdDAM, MdRGL, and MdEBB was altered in transgenic T166 trees relative
      to non-transformed M.26 trees. In particular, several putative MdDAM genes,
      associated with the dormancy-cycle in other species of woody plants in the
      Rosaceae, exhibited different patterns of expression in the T166 vs. M.26 trees.
      Additionally, for the first time a putative APETALA2/Ethylene-responsive
      transcription factor, originally described in poplar and shown to regulate the
      timing of bud break, was shown to be associated with the timing of bud break in
      apple. Since the overexpression of PpCBF1 in apple results in a dramatic
      alteration in cold acclimation, dormancy, and growth, this transgenic line (T166)
      may represent a useful model for studying the integration of these seasonal life
      cycle parameters. 

PMID- 25774160
TI  - Response to elevated CO2 in the temperate C3 grass Festuca arundinaceae across a
      wide range of soils.
AB  - Soils vary widely in mineral nutrient availability and physical characteristics,
      but the influence of this variability on plant responses to elevated CO2 remains
      poorly understood. As a first approximation of the effect of global soil
      variability on plant growth response to CO2, we evaluated the effect of CO2 on
      tall fescue (Festuca arundinacea) grown in soils representing 10 of the 12 global
      soil orders plus a high-fertility control. Plants were grown in small pots in
      continuously stirred reactor tanks in a greenhouse. Elevated CO2 (800 ppm)
      increased plant biomass in the high-fertility control and in two of the more
      fertile soils. Elevated CO2 had variable effects on foliar mineral concentration
      nitrogen was not altered by elevated CO2, and phosphorus and potassium were only
      affected by CO2 in a small number of soils. While leaf photosynthesis was
      stimulated by elevated CO2 in six soils, canopy photosynthesis was not
      stimulated. Four principle components were identified; the first was associated
      with foliar minerals and soil clay, and the second with soil acidity and foliar
      manganese concentration. The third principle component was associated with gas
      exchange, and the fourth with plant biomass and soil minerals. Soils in which
      tall fescue did not respond to elevated CO2 account for 83% of global land area.
      These results show that variation in soil physical and chemical properties have
      important implications for plant responses to global change, and highlight the
      need to consider soil variability in models of vegetation response to global
      change. 

PMID- 25774161
TI  - Proteomic analyses reveal differences in cold acclimation mechanisms in freezing
      tolerant and freezing-sensitive cultivars of alfalfa.
AB  - Cold acclimation in alfalfa (Medicago sativa L.) plays a crucial role in cold
      tolerance to harsh winters. To examine the cold acclimation mechanisms in
      freezing-tolerant alfalfa (ZD) and freezing-sensitive alfalfa (W5), holoproteins,
      and low-abundance proteins (after the removal of RuBisCO) from leaves were
      extracted to analyze differences at the protein level. A total of 84 spots were
      selected, and 67 spots were identified. Of these, the abundance of 49 spots and
      24 spots in ZD and W5, respectively, were altered during adaptation to chilling
      stress. Proteomic results revealed that proteins involved in photosynthesis,
      protein metabolism, energy metabolism, stress and redox and other proteins were
      mobilized in adaptation to chilling stress. In ZD, a greater number of changes
      were observed in proteins, and autologous metabolism and biosynthesis were slowed
      in response to chilling stress, thereby reducing consumption, allowing for
      homeostasis. The capability for protein folding and protein biosynthesis in W5
      was enhanced, which allows protection against chilling stress. The ability to
      perceive low temperatures was more sensitive in freezing-tolerant alfalfa
      compared to freezing-sensitive alfalfa. This proteomics study provides new
      insights into the cold acclimation mechanism in alfalfa. 

PMID- 25774162
TI  - TaNAC1 acts as a negative regulator of stripe rust resistance in wheat, enhances
      susceptibility to Pseudomonas syringae, and promotes lateral root development in
      transgenic Arabidopsis thaliana.
AB  - Plant-specific NAC transcription factors (TFs) constitute a large family and play
      important roles in regulating plant developmental processes and responses to
      environmental stresses, but only some of them have been investigated for effects
      on disease reaction in cereal crops. Virus-induced gene silencing (VIGS) is an
      effective strategy for rapid functional analysis of genes in plant tissues. In
      this study, TaNAC1, encoding a new member of the NAC1 subgroup, was cloned from
      bread wheat and characterized. It is a TF localized in the cell nucleus, and
      contains an activation domain in its C-terminal. TaNAC1 was strongly expressed in
      wheat roots and was involved in responses to infection by the obligate pathogen
      Puccinia striiformis f. sp. tritici and defense-related hormone treatments such
      as salicylic acid (SA), methyl jasmonate, and ethylene. Knockdown of TaNAC1 with
      barley stripe mosaic virus-induced gene silencing (BSMV-VIGS) enhanced stripe
      rust resistance. TaNAC1-overexpression in Arabidopsis thaliana plants gave
      enhanced susceptibility, attenuated systemic-acquired resistance to Pseudomonas
      syringae DC3000, and promoted lateral root development. Jasmonic acid-signaling
      pathway genes PDF1.2 and ORA59 were constitutively expressed in transgenic
      plants. TaNAC1 overexpression suppressed the expression levels of resistance
      related genes PR1 and PR2 involved in SA signaling and AtWRKY70, which functions
      as a connection node between the JA- and SA-signaling pathways. Collectively,
      TaNAC1 is a novel NAC member of the NAC1 subgroup, negatively regulates plant
      disease resistance, and may modulate plant JA- and SA-signaling defense cascades.

PMID- 25774163
TI  - CHRNA4 rs1044396 is associated with smoking cessation in varenicline therapy.
AB  - BACKGROUND: The large individual variability in response to drugs for smoking
      cessation suggests that specific treatments can be more effective in particular
      subgroups of smokers. In the context of personalized medicine, the main aim of
      the present study was to evaluate whether the CHRNA4 and CHRNB2 polymorphisms are
      associated with response to smoking cessation therapies in patients from a smoker
      assistance program. METHODS: This cohort study enrolled 483 smoking patients who
      received behavioral counseling and drug treatment (varenicline, bupropion, and/or
      nicotine replacement therapy). Smoking cessation success was considered for
      patients who completed 6 months of continuous abstinence. Fagerstrom test for
      nicotine dependence (FTND) and Issa situational smoking scores were analyzed for
      nicotine dependence. The CHRNA4 (rs1044396 and rs2236196) and CHRNB2 (rs2072660
      and rs2072661) polymorphisms were genotyped by high resolution melting analysis.
      RESULTS: Patients with rs1044396 CC genotype had lower success rate in treatment
      with varenicline (29.5%) compared with carriers of CT or TT genotypes (50.9%; p =
      0.007, n = 167). The CT or TT genotypes were associated with higher odds ratio
      for success (OR = 1.67, 95% CI = 1.10-2.53, p = 0.02), in a multivariate model.
      We did not observe significant differences in the FTND and Issa scores according
      to the studied polymorphisms. CONCLUSION: The CHRNA4 rs1044396 is associated with
      smoking cessation in individuals on varenicline therapy. We suggest that this
      polymorphism influences the varenicline response, but replications of this
      finding are needed.

PMID- 25774164
TI  - Reference cells and ploidy in the comet assay.
AB  - In the comet assay single cells are analyzed with respect to their level of DNA
      damage. Discrimination of the individual cell or cell type based on DNA content,
      with concomitant scoring of the DNA damage, is useful since this may allow
      analysis of mixtures of cells. Different cells can then be characterized based on
      their ploidy, cell cycle stage, or genome size. We here describe two applications
      of such a cell type-specific comet assay: (i) Testicular cell suspensions,
      analyzed on the basis of their ploidy during spermatogenesis; and (ii) reference
      cells in the form of fish erythrocytes which can be included as internal
      standards to correct for inter-assay variations. With standard fluorochromes used
      in the comet assay, the total staining signal from each cell - whether damaged or
      undamaged - was found to be associated with the cell's DNA content. Analysis of
      the fluorescence intensity of single cells is straightforward since these data
      are available in scoring systems based on image analysis. The analysis of
      testicular cell suspensions provides information on cell type specific
      composition, susceptibility to genotoxicants, and DNA repair. Internal reference
      cells, either untreated or carrying defined numbers of lesions induced by
      ionizing radiation, are useful for investigation of experimental factors that can
      cause variation in comet assay results, and for routine inclusion in experiments
      to facilitate standardization of methods, and comparison of comet assay data
      obtained in different experiments or in different laboratories. They can also be
      used - in combination with a reference curve - to quantify the DNA lesions
      induced by a certain treatment. Fish cells of a range of genome sizes, both
      greater and smaller than human, are suitable for this purpose, and they are
      inexpensive. 

PMID- 25774165
TI  - Morphological and genetic characterization of an emerging Azorean horse breed:
      the Terceira Pony.
AB  - The Terceira Pony is a horse indigenous to Terceira Island in the Azores. These
      horses were very important during the colonization of the island. Due to their
      very balanced proportions and correct gaits, and with an average withers height
      of 1.28 m, the Terceira Pony is often confused with a miniature pure-bred
      Lusitano. This population was officially recognized as the fourth Portuguese
      equine breed by the national authorities in January, 2014. The aim of this study
      was to analyze the morphology and the genetic diversity by means of
      microsatellite markers of this emerging horse breed. The biometric data consisted
      of 28 body measurements and nine angles from 30 animals (11 sires, 19 dams). The
      Terceira Pony is now a recognized horse breed and is gaining in popularity
      amongst breeders and the younger riding classes. The information obtained from
      this study will be very useful for conservation and management purposes,
      including maximizing the breed's genetic diversity, and solidifying the desirable
      phenotypic traits. 

PMID- 25774166
TI  - Bystander communication and cell cycle decisions after DNA damage.
AB  - The DNA damage response (DDR) has two main goals, to repair the damaged DNA and
      to communicate the presence of damaged DNA. This communication allows the
      adaptation of cellular behavior to minimize the risk associated with DNA damage.
      In particular, cell cycle progression must be adapted after a DNA-damaging
      insult, and cells either pause or terminally exit the cell cycle during a DDR. As
      cells can accumulate mutations after a DDR due to error-prone DNA repair,
      terminal cell cycle exit may prevent malignant transformation. The tumor
      suppressor p53 plays a key role in promoting terminal cell cycle exit.
      Interestingly, p53 has been implicated in communication of a stress response to
      surrounding cells, known as the bystander response. Recently, surrounding cells
      have also been shown to affect the damaged cell, suggesting the presence of
      intercellular feedback loops. How such feedback may affect terminal cell cycle
      exit remains unclear, but its presence calls for caution in evaluating cellular
      outcome without controlling the cellular surrounding. In addition, such feedback
      may contribute to how the cellular environment affects malignant transformation
      after DNA damage. 

PMID- 25774167
TI  - Probing entrainment of Ostreococcus tauri circadian clock by green and blue light
      through a mathematical modeling approach.
AB  - Most organisms anticipate daily environmental variations and orchestrate cellular
      functions thanks to a circadian clock which entrains robustly to the day/night
      cycle, despite fluctuations in light intensity due to weather or seasonal
      variations. Marine organisms are also subjected to fluctuations in light spectral
      composition as their depth varies, due to differential absorption of different
      wavelengths by sea water. Studying how light input pathways contribute to
      circadian clock robustness is therefore important. Ostreococcus tauri, a
      unicellular picoplanktonic marine green alga with low genomic complexity and
      simple cellular organization, has become a promising model organism for systems
      biology. Functional and modeling approaches have shown that a core circadian
      oscillator based on orthologs of Arabidopsis TOC1 and CCA1 clock genes accounts
      for most experimental data acquired under a wide range of conditions. Some
      evidence points at putative light input pathway(s) consisting of a two-component
      signaling system (TCS) controlled by the only two histidine kinases (HK) of O.
      tauri. LOV-HK is a blue light photoreceptor under circadian control, that is
      required for circadian clock function. An involvement of Rhodopsin-HK (Rhod-HK)
      is also conceivable since rhodopsin photoreceptors mediate blue to green light
      input in animal circadian clocks. Here, we probe the role of LOV-HK and Rhod-HK
      in mediating light input to the TOC1-CCA1 oscillator using a mathematical model
      incorporating the TCS hypothesis. This model agrees with clock gene expression
      time series representative of multiple environmental conditions in blue or green
      light, characterizing entrainment by light/dark cycles, free-running in constant
      light, and resetting. Experimental and theoretical results indicate that both
      blue and green light can reset O. tauri circadian clock. Moreover, our
      mathematical analysis suggests that Rhod-HK is a blue-green light receptor and
      drives the clock together with LOV-HK. 

PMID- 25774170
TI  - Gastrodin inhibits neuroinflammation in rotenone-induced Parkinson's disease
      model rats.
AB  - The present study showed that the latency of rats moving on a vertical grid was
      significantly prolonged, and the number of rats sliding down from the declined
      plane was increased remarkably, in rotenone-induced Parkinson's disease model
      rats compared with control rats. The moving latency recovered to normal levels,
      but the number of slides was significantly increased at 28 days after model
      establishment. The slope test is a meaningful approach to evaluate the symptoms
      of Parkinson's disease model rats treated with rotenone. In addition, loss of
      substantia nigral dopaminergic neurons in model rats was observed at 1 day after
      the model was established, and continued gradually at 14 and 28 days. The
      expression of tyrosine hydroxylase-positive cells was significantly increased in
      gastrodin-treated rats at 14 days. Significant numbers of activated microglia
      cells were observed in model rats at 14 and 28 days; treatment of rats with
      Madopar at 28 days suppressed microglial activation. Treatment of rats with
      gastrodin or Madopar at 28 days significantly reduced interleukin-1beta
      expression. The loss of substantia nigral dopaminergic neurons paralleled the
      microglial activation in Parkinson's disease model rats treated with rotenone.
      The inflammatory factors tumor necrosis factor-alpha and interleukin-1beta are
      involved in the substantia nigral damage. Gastrodin could protect dopaminergic
      neurons via inhibition of interleukin-1beta expression and neuroinflammation in
      the substantia nigra. 

PMID- 25774168
TI  - Targeting lung cancer through inhibition of checkpoint kinases.
AB  - Inhibitors of checkpoint kinases ATR, Chk1, and Wee1 are currently being tested
      in preclinical and clinical trials. Here, we review the basic principles behind
      the use of such inhibitors as anticancer agents, and particularly discuss their
      potential for treatment of lung cancer. As lung cancer is one of the most deadly
      cancers, new treatment strategies are highly needed. We discuss how checkpoint
      kinase inhibition in principle can lead to selective killing of lung cancer cells
      while sparing the surrounding normal tissues. Several features of lung cancer may
      potentially be exploited for targeting through inhibition of checkpoint kinases,
      including mutated p53, low ERCC1 levels, amplified Myc, tumor hypoxia and
      presence of lung cancer stem cells. Synergistic effects have also been reported
      between inhibitors of ATR/Chk1/Wee1 and conventional lung cancer treatments, such
      as gemcitabine, cisplatin, or radiation. Altogether, inhibitors of ATR, Chk1, and
      Wee1 are emerging as new cancer treatment agents, likely to be useful in lung
      cancer treatment. However, as lung tumors are very diverse, the inhibitors are
      unlikely to be effective in all patients, and more work is needed to determine
      how such inhibitors can be utilized in the most optimal ways. 

PMID- 25774169
TI  - The role of non-coding RNAs in the regulation of stem cells and progenitors in
      the normal mammary gland and in breast tumors.
AB  - The outlook on stem cell (SC) biology is shifting from a rigid hierarchical to a
      more flexible model in which the identity and the behavior of adult SCs, far from
      being fixed, are determined by the dynamic integration of cell autonomous and non
      autonomous mechanisms. Within this framework, the recent discovery of thousands
      of non-coding RNAs (ncRNAs) with regulatory function is redefining the landscape
      of transcriptome regulation, highlighting the interplay of epigenetic,
      transcriptional, and post-transcriptional mechanisms in the specification of cell
      fate and in the regulation of developmental processes. Furthermore, the
      expression of ncRNAs is often tissue- or even cell type-specific, emphasizing
      their involvement in defining space, time and developmental stages in gene
      regulation. Such a role of ncRNAs has been investigated in embryonic and induced
      pluripotent SCs, and in numerous types of adult SCs and progenitors, including
      those of the breast, which will be the topic of this review. We will focus on
      ncRNAs with an important role in breast cancer, in particular in mammary cancer
      SCs and progenitors, and highlight the ncRNA-based circuitries whose subversion
      alters a number of the epigenetic, transcriptional, and post-transcriptional
      events that control "stemness" in the physiological setting. 

PMID- 25774171
TI  - Analysis of hippocampal gene expression profile of Alzheimer's disease model rats
      using genome chip bioinformatics.
AB  - In this study, an Alzheimer's disease model was established in rats through
      stereotactic injection of condensed amyloid beta 1-40 into the bilateral
      hippocampus, and the changes of gene expression profile in the hippocampus of rat
      models and sham-operated rats were compared by genome expression profiling
      analysis. Results showed that the expression of 50 genes was significantly up
      regulated (fold change >= 2), while 21 genes were significantly down-regulated in
      the hippocampus of Alzheimer's disease model rats (fold change <= 0.5) compared
      with the sham-operation group. The differentially expressed genes are involved in
      many functions, such as brain nerve system development, neuronal differentiation
      and functional regulation, cellular growth, differentiation and apoptosis,
      synaptogenesis and plasticity, inflammatory and immune responses, ion
      channels/transporters, signal transduction, cell material/energy metabolism. Our
      findings indicate that several genes were abnormally expressed in the metabolic
      and signal transduction pathways in the hippocampus of amyloid beta 1-40-induced
      rat model of Alzheimer's disease, thereby affecting the hippocampal and brain
      functions. 

PMID- 25774172
TI  - Two memory associated genes regulated by amyloid precursor protein intracellular
      domain: Novel insights into the pathogenesis of learning and memory impairment in
      Alzheimer's disease.
AB  - In this study, we employed chromatin immunoprecipitation, a useful method for
      studying the locations of transcription factors bound to specific DNA regions in
      specific cells, to investigate amyloid precursor protein intracellular domain
      binding sites in chromatin DNA from hippocampal neurons of rats, and to screen
      out five putative genes associated with the learning and memory functions. The
      promoter regions of the calcium/calmodulin-dependent protein kinase II alpha and
      glutamate receptor-2 genes were amplified by PCR from DNA products
      immunoprecipitated by amyloid precursor protein intracellular domain. An
      electrophoretic mobility shift assay and western blot analysis suggested that the
      promoter regions of these two genes associated with learning and memory were
      bound by amyloid precursor protein intracellular domain (in complex form). Our
      experimental findings indicate that the amyloid precursor protein intracellular
      domain is involved in the transcriptional regulation of learning- and memory
      associated genes in hippocampal neurons. These data may provide new insights into
      the molecular mechanism underlying the symptoms of progressive memory loss in
      Alzheimer's disease. 

PMID- 25774173
TI  - Brain-derived neurotrophic factor prevents beta- amyloid-induced apoptosis of
      pheochromocytoma cells by regulating Bax/Bcl-2 expression.
AB  - Brain-derived neurotrophic factor was utilized in the present study to treat cell
      injury models induced by aggregated beta-amyloid(25-35). Methylthiazolyldiphenyl
      tetrazolium bromide assay and western blot analysis showed that brain-derived
      neurotrophic factor provided neuroprotection against cellular apoptosis by
      suppressing the decline in beta-amyloid(25-35)-induced cell activity and the
      increasing ratio of Bax/Bcl-2. After treating pheochromocytoma cells with
      tyrosine kinase receptor B receptor inhibitor K252a, brain-derived neurotrophic
      factor reverses the above-mentioned changes. The experimental findings suggested
      that brain-derived neurotrophic factor prevented beta-amyloid peptide-induced
      cellular apoptosis by modulating Bax/Bcl-2 expression, and this effect was
      associated with binding to the specific tyrosine kinase receptor B receptor. 

PMID- 25774175
TI  - NG2 expression in rats with acute T10 spinal cord injury.
AB  - Rat models of T10 spinal cord injury were established with a clamp method. NG2
      expression was detected with immunohistochemical staining and western blot. Ten
      days after spinal cord injury, the number of NG2-positive cells in the damaged
      areas and NG2 absorbance were both significantly increased. The findings indicate
      that acute T10 spinal cord injury in rats can lead to upregulation of NG2 protein
      expression in damaged areas. 

PMID- 25774174
TI  - Long-term anodal block stimulation at sacral anterior roots promoted recovery of
      neurogenic bladder function in a rabbit model of complete spinal cord injury.
AB  - A complete spinal cord injury model was established in experimental rabbits using
      the spinal cord clip compression method. Urodynamic examination was performed 2
      weeks later to determine neurogenic bladder status. The rabbits were treated with
      anodal block stimulation at sacral anterior roots for 4 weeks. Electrical
      stimulation of sacral anterior roots improved urodynamic parameters of neurogenic
      bladder in rabbit models of complete spinal cord injury, effectively promoted
      urinary function, and relieved urinary retention. Immunohistochemistry results
      showed that a balance was achieved among expression of muscarinic receptor
      subunits M2, M3, ATP-gated ion channel P2X3 receptors, and beta2-adrenergic
      receptor, and nerve growth factor expression decreased. These results suggested
      that long-term sacral anterior root stimulation of anodal block could be used to
      treat neurogenic bladder in a rabbit model of complete spinal cord injury. 

PMID- 25774176
TI  - Fluoro-ruby retrograde tracing and three- dimensional visualization of the
      corticospinal tract in the guinea pig.
AB  - Fluoro-ruby was injected into the posterior funiculus of the spinal cord in the
      cervical (C5-T2) and lumbar (L3-6) segments of adult guinea pigs. The spinal cord
      was cut into serial frozen sections. The Fluoro-ruby labeling was clearly
      delineated from the surrounding structure. The labeling traversed the cervical,
      thoracic and lumbar segments, and was located on the ventral portion of the
      posterior funiculus on the injected side, proximal to the intermediate zone of
      the dorsal gray matter. The fluorescence area narrowed rostro-caudally. The
      spinal cord, spinal cord gray matter and corticospinal tract were reconstructed
      using 3D-DOCTOR 4.0 software, resulting in a robust three-dimensional profile.
      Using functionality provided by the reconstruction software, free multi-angle
      observation and sectioning could be conducted on the spinal cord and
      corticospinal tract. Our experimental findings indicate that the Fluoro-ruby
      retrograde fluorescent tracing technique can accurately display the anatomical
      location of corticospinal tract in the guinea pig and that three-dimensional
      reconstruction software can be used to provide a three-dimensional image of the
      corticospinal tract. 

PMID- 25774177
TI  - Protein expression of sensory and motor nerves: Two-dimensional gel
      electrophoresis and mass spectrometry.
AB  - The present study utilized samples from bilateral motor branches of the femoral
      nerve, as well as saphenous nerves, ventral roots, and dorsal roots of the spinal
      cord, to detect differential protein expression using two-dimensional gel
      electrophoresis and nano ultra-high performance liquid chromatography
      electrospray ionization mass spectrometry tandem mass spectrometry techniques. A
      mass spectrum was identified using the Mascot search. Results revealed
      differential expression of 11 proteins, including transgelin, Ig kappa chain
      precursor, plasma glutathione peroxidase precursor, an unnamed protein product
      (gi|55628), glyceraldehyde-3-phosphate dehydrogenase-like protein,
      lactoylglutathione lyase, adenylate kinase isozyme 1, two unnamed proteins
      products (gi|55628 and gi|1334163), and poly(rC)-binding protein 1 in motor and
      sensory nerves. Results suggested that these proteins played roles in specific
      nerve regeneration following peripheral nerve injury and served as specific
      markers for motor and sensory nerves. 

PMID- 25774178
TI  - Oxidative stress in neurodegenerative diseases.
AB  - Reactive oxygen species are constantly produced in aerobic organisms as by
      products of normal oxygen metabolism and include free radicals such as superoxide
      anion (O2 (-)) and hydroxyl radical (OH(-)), and non-radical hydrogen peroxide
      (H2O2). The mitochondrial respiratory chain and enzymatic reactions by various
      enzymes are endogenous sources of reactive oxygen species. Exogenous reactive
      oxygen species -inducing stressors include ionizing radiation, ultraviolet light,
      and divergent oxidizing chemicals. At low concentrations, reactive oxygen species
      serve as an important second messenger in cell signaling; however, at higher
      concentrations and long-term exposure, reactive oxygen species can damage
      cellular macromolecules such as DNA, proteins, and lipids, which leads to
      necrotic and apoptotic cell death. Oxidative stress is a condition of imbalance
      between reactive oxygen species formation and cellular antioxidant capacity due
      to enhanced ROS generation and/or dysfunction of the antioxidant system.
      Biochemical alterations in these macromolecular components can lead to various
      pathological conditions and human diseases, especially neurodegenerative
      diseases. Neurodegenerative diseases are morphologically featured by progressive
      cell loss in specific vulnerable neuronal cells, often associated with
      cytoskeletal protein aggregates forming inclusions in neurons and/or glial cells.
      Deposition of abnormal aggregated proteins and disruption of metal ions
      homeostasis are highly associated with oxidative stress. The main aim of this
      review is to present as much detailed information as possible that is available
      on various neurodegenerative disorders and their connection with oxidative
      stress. A variety of therapeutic strategies designed to address these
      pathological processes are also described. For the future therapeutic direction,
      one specific pathway that involves the transcription factor nuclear factor
      erythroid 2-related factor 2 is receiving considerable attention. 

PMID- 25774179
TI  - Neural plasticity after spinal cord injury.
AB  - Plasticity changes of uninjured nerves can result in a novel neural circuit after
      spinal cord injury, which can restore sensory and motor functions to different
      degrees. Although processes of neural plasticity have been studied, the mechanism
      and treatment to effectively improve neural plasticity changes remain
      controversial. The present study reviewed studies regarding plasticity of the
      central nervous system and methods for promoting plasticity to improve repair of
      injured central nerves. The results showed that synaptic reorganization, axonal
      sprouting, and neurogenesis are critical factors for neural circuit
      reconstruction. Directed functional exercise, neurotrophic factor and
      transplantation of nerve-derived and non-nerve-derived tissues and cells can
      effectively ameliorate functional disturbances caused by spinal cord injury and
      improve quality of life for patients. 

PMID- 25774180
TI  - Detrimental impact of hyperlipidemia on the peripheral nervous system: A novel
      target of medical epidemiological and fundamental research study.
AB  - Recently, epidemiological studies on the etiology of peripheral neuropathies have
      revealed that hyperlipidemia is a novel risk factor. Plasma lipid levels were
      confirmed to be associated with the incidence of many peripheral neuropathies
      including axonal distal polyneuropathy, vision and hearing loss, motor nerve
      system lesions and sympathetic nerve system dysfunction. Moreover, different
      lipid components such as cholesterol, triacylglycerols and lipoprotein are
      involved in the pathogenesis of these neuropathies. This review aimed to discuss
      the effect of hyperlipidemia on the peripheral nervous system and its association
      with peripheral neuropathies. Furthermore, a detailed discussion focusing on the
      explicit mechanisms related to hyperlipidemia-induced peripheral neuropathies is
      presented here. These mechanisms, including intracellular oxidative stress,
      inflammatory lesions, ischemia and dysregulation of local lipid metabolism, share
      pathways and interact mutually. In addition, we examined current information on
      clinical trials to prevent and treat peripheral neuropathies caused by
      hyperlipidemia, with a predictive discussion regarding the orientation of future
      investigations. 

PMID- 25774181
TI  - Protective effects of curcumin in APPswe transfected SH-SY5Y cells.
AB  - The APPswe plasmid was transfected into the neuroblastoma cell line SH-SY5Y to
      establish a cell model of Alzheimer's disease. Graded concentration and time
      course experiments demonstrate that curcumin significantly upregulates
      phosphatidylinositol 3-kinase (PI3K), Akt, nuclear factor E2-related factor-2
      (Nrf2), heme oxygenase 1 and ferritin expression, and that it significantly
      downregulates heme oxygenase 2, reactive oxygen species and amyloid-beta 40/42
      expression. These effects of curcumin on PI3K, Akt and Nrf2 were blocked by
      LY294002 (PI3k inhibitor) and NF-E2-related factor-2 siRNA. The results indicate
      that the cytoprotection conferred by curcumin on APPswe transfected SH-SY5Y cells
      is mediated by its ability to regulate the balance between heme oxygenase 1 and 2
      via the PI3K/Akt/Nrf2 intracellular signaling pathway. 

PMID- 25774182
TI  - Protective effects of kidney-tonifying Chinese herbal preparation on substantia
      nigra neurons in a mouse model of Parkinson's disease.
AB  - The Chinese herbs Herba Epimedii, Fructus Ligustri Lucidi and Rhizoma Polygonati
      were injected into Parkinson's disease mice established via intraperitoneal
      injection of 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine hydrochloride. The
      selective monoamine oxidase B inhibitor selegiline was used as a positive control
      drug. After successive administration for 4 weeks, Herba Epimedii could
      downregulate the expression of caspase-3 and increase the brain-derived
      neurotrophic factor level, as well as increase tyrosine hydroxylase activity in
      the substantia nigra of Parkinson's disease mouse models. Rhizoma Polygonati
      could downregulate the expression of caspase-3 and FasL, and increase neural
      growth factor and brain-derived neurotrophic factor levels. Fructus Ligustri
      Lucidi could downregulate caspase-3 expression. Rhizoma Polygonati and Fructus
      Ligustri Lucidi did not produce obvious effects on tyrosine hydroxylase activity.
      Herba Epimedii and Fructus Ligustri Lucidi yielded similar effects on apoptosis
      promoting factors to those elicited by selegiline. Herba Epimedii and Rhizoma
      Polygonati significantly increased the levels of neurotrophic factors compared
      with selegiline. Herba Epimedii significantly increased tyrosine hydroxylase
      activity compared with selegiline. It is indicated that the kidney-tonifying
      Chinese herbal preparation can downregulate the expression of apoptosis-promoting
      factors, increase neurotrophic factors levels in the substantia nigra and
      striatum, as well as increase tyrosine hydroxylase activity in the substantia
      nigra of Parkinson's disease mouse models, thereby exerting a stronger or similar
      neuroprotective effects compared with selegiline. 

PMID- 25774183
TI  - Puerarin decreases hypoxia inducible factor-1 alpha in the hippocampus of
      vascular dementia rats.
AB  - In this study, a rat vascular dementia model was established by permanent
      bilateral common carotid arterial occlusion. Rats were intraperitoneally injected
      with puerarin 3 days before modeling, for 45 successive days. Results
      demonstrated that in treated animals hippocampal structures were clear, nerve
      cells arranged neatly, and cytoplasm was rich in Nissl bodies. The number of
      cells positive for hypoxia inducible factor-1 alpha, erythropoietin and
      endothelial nitric oxide synthase was reduced; and the learning and memory
      abilities of rats were significantly improved. Our experimental findings indicate
      that puerarin can significantly improve learning and memory in a vascular
      dementia model, and that the underlying mechanism may be associated with the
      regulation of the expression of hypoxia inducible factor-1 alpha. 

PMID- 25774184
TI  - Scorpion ethanol extract and valproic acid effects on hippocampal glial
      fibrillary acidic protein expression in a rat model of chronic-kindling epilepsy
      induced by lithium chloride-pilocarpine.
AB  - The present study analyzed the effects of ethanol extracts of scorpion on
      epilepsy prevention and hippocampal expression of glial fibrillary acidic protein
      in a lithium chloride-pilocarpine epileptic rat model. Results were subsequently
      compared with valproic acid. Results showed gradually-increased hippocampal glial
      fibrillary acidic protein expression following model establishment; glial
      fibrillary acidic protein mRNA expression was significantly increased at 3 days,
      reached a peak at 7 days, and then gradually decreased thereafter. Ethanol
      extracts of scorpion doses of 580 and 1 160 mg/kg, as well as 120 mg/kg valproic
      acid, led to a decreased number of glial fibrillary acidic protein-positive cells
      and glial fibrillary acidic protein mRNA expression, as well as decreased seizure
      grades and frequency of spontaneously recurrent seizures. The effects of 1 160
      mg/kg ethanol extracts of scorpion were equal to those of 120 mg/kg valproic
      acid. These results suggested that the anti-epileptic effect of ethanol extracts
      of scorpion were associated with decreased hippocampal glial fibrillary acidic
      protein expression in a rat model of lithium chloride-pilocarpine induced
      epilepsy. 

PMID- 25774186
TI  - Effect of borneol, moschus, storax, and acorus tatarinowii on expression levels
      of four amino acid neurotransmitters in the rat corpus striatum.
AB  - The present study collected cerebrospinal fluid samples from the corpus striatum
      in rats treated with borneol, moschus, storax, and acorus tatarinowii using brain
      microdialysis technology. Levels of excitatory neurotransmitters aspartic acid
      and glutamate, as well as inhibitory neurotransmitters glycine and gamma
      aminobutyric acid, were measured in samples using reversed-phase high-performance
      liquid chromatography, phosphate gradient elution, and fluorescence detection.
      Results showed that concentrations of all four amino acid neurotransmitters
      significantly increased in the corpus striatum following treatment with borneol
      or moschus, but effects due to borneol were more significant than moschus. Acorus
      tatarinowii treatment increased gamma-aminobutyric acid expression, but decreased
      glutamate concentrations. Storax increased aspartic acid concentrations and
      decreased glycine expression. Results demonstrated that borneol and moschus
      exhibited significant effects on con amino acid neurotransmitter expression;
      storax exhibited excitatory effects, and acorus tatarinowii resulted in
      inhibitory effects. 

PMID- 25774185
TI  - Yizhi Xingnao prescription improves the cognitive function of patients after a
      transient ischemic attack.
AB  - Patients with mild cognitive impairment after a transient ischemic attack were
      included in this study. They were treated with Yizhi Xingnao prescription,
      ergoloid mesylates or aspirin for 60 days. Evaluation using the Montreal
      Cognitive Assessment Scale showed that cognitive function was significantly
      improved in all patients, especially after the combined treatment of Yizhi
      Xingnao and aspirin. The scores from the Montreal Cognitive Assessment Scale were
      improved overall and the effective treatment rate was as high as 79%, which was
      higher than patients treated with a combination of ergoloid mesylates and
      aspirin, or aspirin alone. Our experimental findings indicate that Yizhi Xingnao
      prescription can improve mild cognitive impairment after a transient ischemic
      attack, and that it is more effective than ergoloid mesylates. 

PMID- 25774187
TI  - 7, 8-dihydroxycoumarin improves neurological function in a mouse model of sciatic
      nerve injury.
AB  - In the present study, a mouse model of sciatic nerve injury was treated with
      intraperitoneal injection of 7, 8-dihydroxycoumarin (10, 5, or 2.5 mg/kg per
      day). Western blot and real-time PCR results showed that growth associated
      protein 43 expression was significantly increased in the L4-6 segments of the
      spinal cord. The amplitude and velocity of motor nerve conduction in the sciatic
      nerve were significantly increased in model mice. In addition, the appearance of
      the myelin sheath in the injured sciatic nerve was regular, with an even
      thickness and clear outline, and the surrounding fibroplasia was not obvious. Our
      results indicate that 7, 8-dihydroxycoumarin can promote the repair of injured
      nerve by upregulating growth associated protein 43 expression in the
      corresponding spinal cord segments of mice with sciatic nerve injury. 

PMID- 25774188
TI  - Dynamic functional connectivity analysis of Taichong (LR3) acupuncture effects in
      various brain regions.
AB  - The present study conducted a multi-scale dynamic functional connectivity
      analysis to evaluate dynamic behavior of acupuncture at Taichong (LR3) and sham
      acupoints surrounding Taichong. Results showed differences in wavelet transform
      coherence characteristic curves in the declive, precuneus, postcentral gyrus,
      supramarginal gyrus, and occipital lobe between acupuncture at Taichong and
      acupuncture at sham acupoints. The differences in characteristic curves revealed
      that the specific effect of acupuncture existed during the post-acupuncture rest
      state and lasted for 5 minutes. 

PMID- 25774189
TI  - Electroacupuncture effects on cortical neurons, as well as Janus kinase 2-signal
      transducer and activator of transcription 3 signal transduction pathway, in a rat
      model of cerebral ischemia.
AB  - The present study established a model of focal cerebral ischemia through heat
      coagulation induced occlusion of the middle cerebral artery. Following
      electroacupuncture at Baihui (GV20) and Dazhui (GV14), or intracerebroventricular
      infusion of AG490, a Janus kinase 2 phosphorylation inhibitor, the amount of
      necrotic or degenerated neurons in the ischemic cerebral cortex decreased,
      neuronal swelling was ameliorated, and expression of phosphorylated Janus kinase
      2 and signal transducer and activator of transcription 3 decreased. Results
      confirmed that electroacupuncture promoted neuronal repair in the cerebral cortex
      by reducing expression of phosphorylated Janus kinase 2 and signal transducer and
      activator of transcription 3, as well as weakening the phosphorylated activation,
      thereby blocking abnormal activation of the Janus kinase 2- signal transducer and
      activator of transcription 3 signal transduction pathway. 

PMID- 25774190
TI  - An epidemiologic study of mitochondrial membrane transporter protein gene
      polymorphism and risk factors for neural tube defects in Shanxi, China.
AB  - The present study involved a questionnaire survey of 156 mothers that gave birth
      to children with neural tube defects or had a history of pregnancy resulting in
      children with neural tube defects (case group) and 156 control mothers with
      concurrent healthy children (control group) as well as detection of mitochondrial
      membrane transporter protein gene [uncoupling protein 2 (UCP2)] polymorphism. The
      maternal UCP2 3' untranslated region (UTR) D/D genotype and D allele frequency
      were significantly higher in the case group compared with the control group (odds
      ratio (OR) 3.233; 95% confidence interval (CI) 1.103-9.476; P = 0.040; OR: 3.484;
      95% CI: for neural tube defects 2.109-5.753; P < 0.001). Univariate and
      multivariate logistic regression analysis of risk factors for neural tube defects
      showed that a maternal UCP2 3' UTR D/D genotype was negatively interacted with
      the mothers' consumption of frequent fresh fruit and vegetables (S = 0.007),
      positively interacted with the mothers' frequency of germinated potato
      consumption (S = 2.15) and positively interacted with the mothers' body mass
      index (S = 3.50). These findings suggest that maternal UCP2 3' UTR gene
      polymorphism, pregnancy time, consumption of germinated potatoes and body mass
      index are associated with an increased risk for neural tube defects in children
      from mothers living in Shanxi province, China. Moreover, there is an apparent
      gene-environment interaction involved in the development of neural tube defects
      in offspring. 

PMID- 25774191
TI  - Sudden cardiac arrest in a patient with epilepsy induced by chronic inflammation
      on the cerebral surface.
AB  - The present study analyzed a patient with epilepsy due to chronic inflammation on
      the cerebral surface underwent sudden cardiac arrest. Paradoxical brain
      discharge, which occurred prior to epileptic seizures, induced a sudden cardiac
      arrest. However, when the focal brain pressure was relieved, cardiac arrest
      disappeared. A 27-year-old male patient underwent pre-surgical video
      electroencephalogram monitoring for 160 hours. During monitoring, secondary tonic
      clonic seizures occurred five times. A burst of paradoxical brain discharges
      occurred at 2-19 seconds (mean 8 seconds) prior to epileptic seizures. After 2-3
      seconds, sudden cardiac arrest occurred and lasted for 12-22 seconds (average 16
      seconds). The heart rate subsequently returned to a normal rate. Results revealed
      arachnoid pachymenia and adhesions, as well as mucus on the focal cerebral
      surface, combined with poor circulation and increased pressure. Intracranial
      electrodes were placed using surgical methods. Following removal of the arachnoid
      adhesions and mucus on the local cerebral surface, paradoxical brain discharge
      and epileptic seizures occurred three times, but sudden cardiac arrest was not
      recorded during 150-hour monitoring. Post-surgical histological examination
      indicated meningitis. Experimental findings suggested that paradoxical brain
      discharge led to cardiac arrest instead of epileptic seizures; the insult was
      associated with chronic inflammation on the cerebral surface, which subsequently
      led to hypertension and poor blood circulation in focal cerebral areas. 

PMID- 25774192
TI  - The usefulness of diffusion tensor imaging in detection of diffuse axonal injury
      in a patient with head trauma.
AB  - Diffuse axonal injury is the predominant mechanism of injuries in patients with
      traumatic brain injury. Neither conventional brain computed tomography nor
      magnetic resonance imaging has shown sufficient sensitivity in the diagnosis of
      diffuse axonal injury. In the current study, we attempted to demonstrate the
      usefulness of diffusion tensor imaging in the detection of lesion sites of
      diffuse axonal injury in a patient with head trauma who had been misdiagnosed as
      having a stroke. A 44-year-old man fell from a height of about 2 m. Brain
      magnetic resonance imaging (32 months after onset) showed leukomalactic lesions
      in the isthmus of the corpus callosum and the left temporal lobe. He presented
      with mild quadriparesis, intentional tremor of both hands, and trunkal ataxia.
      From diffusion tensor imaging results of 33 months after traumatic brain injury
      onset, we found diffuse axonal injury in the right corticospinal tract (centrum
      semiovale, pons), both fornices (columns and crus), and both inferior cerebellar
      peduncles (cerebellar portions). We think that diffusion tensor imaging could be
      a useful tool in the detection of lesion sites of diffuse axonal injury in
      patients with head trauma. 

PMID- 25774193
TI  - Nucleotide sequence conservation of novel and established cis-regulatory sites
      within the tyrosine hydroxylase gene promoter.
AB  - Tyrosine hydroxylase (TH) is the rate-limiting enzyme in catecholamine
      biosynthesis and its gene proximal promoter ( < 1 kb upstream from the
      transcription start site) is essential for regulating transcription in both the
      developing and adult nervous systems. Several putative regulatory elements within
      the TH proximal promoter have been reported, but evolutionary conservation of
      these elements has not been thoroughly investigated. Since many vertebrate
      species are used to model development, function and disorders of human
      catecholaminergic neurons, identifying evolutionarily conserved transcription
      regulatory mechanisms is a high priority. In this study, we align TH proximal
      promoter nucleotide sequences from several vertebrate species to identify
      evolutionarily conserved motifs. This analysis identified three elements (a TATA
      box, cyclic AMP response element (CRE) and a 5'-GGTGG-3' site) that constitute
      the core of an ancient vertebrate TH promoter. Focusing on only eutherian
      mammals, two regions of high conservation within the proximal promoter were
      identified: a ~250 bp region adjacent to the transcription start site and a ~85
      bp region located approximately 350 bp further upstream. Within both regions,
      conservation of previously reported cis-regulatory motifs and human single
      nucleotide variants was evaluated. Transcription reporter assays in a TH 
      expressing cell line demonstrated the functionality of highly conserved motifs in
      the proximal promoter regions and electromobility shift assays showed that brain
      region specific complexes assemble on these motifs. These studies also identified
      a non-canonical CRE binding (CREB) protein recognition element in the proximal
      promoter. Together, these studies provide a detailed analysis of evolutionary
      conservation within the TH promoter and identify potential cis-regulatory motifs
      that underlie a core set of regulatory mechanisms in mammals.

PMID- 25774194
TI  - Growth hormone treatment and risk of malignancy.
AB  - Growth hormone (GH) treatment has been increasingly widely used for children with
      GH deficiencies as the survival rate of pediatric patients with malignancies has
      increased. Both GH and insulin-like growth factor-I have mitogenic and
      antiapoptotic activity, prompting concern that GH treatment may be associated
      with tumor development. In this review, the authors examined the relationship
      between GH treatment and cancer risk in terms of de novo malignancy, recurrence,
      and secondary neoplasm. Although the results from numerous studies were not
      entirely consistent, this review of various clinical and epidemiological studies
      demonstrated that there is no clear evidence of a causal relationship between GH
      treatment and tumor development. Nonetheless, a small number of studies reported
      that childhood cancer survivors who receive GH treatment have a small increased
      risk of developing de novo cancer and secondary malignant neoplasm. Therefore,
      regular follow-ups and careful examination for development of cancer should be
      required in children who receive GH treatment. Continued surveillance for an
      extended period is essential for monitoring long-term safety. 

PMID- 25774195
TI  - Debriefing in pediatrics.
AB  - Debriefing is a conversational session that revolves around the sharing and
      examining of information after a specific event has taken place. Debriefing may
      follow a simulated or actual experience and provides a forum for the learners to
      reflect on the experience and learn from their mistakes. Originating from the
      military and aviation industry, it is used on a daily basis to reflect and
      improve the performance in other high-risk industries. Expert debriefers may
      facilitate the reflection by asking open-ended questions to probe into the
      framework of the learners and apply lessons learned to future situations.
      Debriefing has been proven to improve clinical outcomes such as the return of
      spontaneous circulation after cardiac arrest and the teaching of teamwork and
      communication in pediatrics. Incorporating debriefing into clinical practice
      would facilitate the cultural change necessary to talk more openly about team
      performance and learn from near misses, errors, and successes that will improve
      not only clinical outcome but also patient safety. 

PMID- 25774196
TI  - Postnatal weight gain in the first two weeks as a predicting factor of severe
      retinopathy of prematurity requiring treatment.
AB  - PURPOSE: This study aimed to investigate the relative weight gain at 2-week
      intervals up to 6 weeks after birth to predict retinopathy of prematurity (ROP)
      requiring treatment among very low birth weight infants. METHODS: A total of 211
      preterm infants with birth weights <1,500 g and gestational age <32 weeks were
      retrospectively reviewed. The main outcome was the development of ROP requiring
      treatment. Body weight measurements were recorded daily. Relative weight gains
      (g/kg/day) were calculated at the second, fourth, and sixth week after birth.
      RESULTS: Of the 211 infants, 89 developed ROP, of which 41 spontaneously
      regressed and 48 with early treatment of ROP type I required laser treatment. The
      relative weight gain at 2, 4, and 6 weeks postnatal age was significantly lower
      in infants with ROP requiring treatment than in infants without ROP or those with
      spontaneous regression (P<0.001, P=0.005, and P=0.004, respectively). On logistic
      regression, poor relative weight gain in the first 2 weeks was found to be
      related to ROP requiring treatment (adjusted odds ratio, 0.809; 95% confidence
      interval, 0.695-0.941; P=0.006). Relative weight gain at 2 weeks postnatal age
      was significantly lower in infants with ROP requiring treatment compared to that
      in ROP requiring no treatment (P=0.012). CONCLUSION: Poor postnatal weight gain
      in the first 2 weeks of life is an important and independent risk factor for ROP
      requiring treatment. Postnatal weight gain can predict the development of severe
      ROP requiring treatment.

PMID- 25774197
TI  - The relationship between primary headache and constipation in children and
      adolescents.
AB  - PURPOSE: Many patients presenting with headache also complain of constipation;
      the relationship between these two symptoms has not been explored in detail. The
      aim of this study was to investigate the association between primary headache and
      constipation. METHODS: This retrospective study included all children who
      attended the Inje University Sanggye Paik Hospital complaining of headache, and
      who had been followed up for at least 100 days. Patients were divided into 2
      groups: group A, in whom the headache improved after treatment for constipation,
      and group B, in whom headache was not associated with constipation. RESULTS: Of
      the 96 patients with primary headache, 24 (25.0%) also had constipation (group
      A). All 24 received treatment for constipation. Follow-up revealed an improvement
      in both headache and constipation in all patients. Group B contained the
      remaining 72 children. Comparison of groups A and B indicated a significant
      difference in sex ratio (P=0.009, chi-square test). Patients with probable
      tension-type headache were more likely to be in Group A (P=0.006, chi-square
      test). CONCLUSION: Resolution of constipation improves headache in many patients
      diagnosed with primary headache, especially those with probable tension-type
      headache. We suggest that either constipation plays a key role in triggering
      headache, or that both constipation and headache share a common pathophysiology.

PMID- 25774198
TI  - Screening for depression and anxiety disorder in children with headache.
AB  - PURPOSE: The purpose of this study was to investigate the importance of initial
      screening tests for depression and anxiety disorders in children with headache.
      In addition, this study evaluated whether the Children's Depression Inventory
      (CDI) and Revised Children's Manifest Anxiety Scale (RCMAS) are suitable for
      screening symptoms of depression and anxiety. METHODS: A retrospective chart
      review was conducted of 720 children aged 7-17 years who had visited a pediatric
      neurology clinic for headaches and were referred to a pediatric psychiatric
      clinic for psychiatric symptoms from January 2010 to December 2011. All patients
      completed the CDI and RCMAS. Among them, charts of patients with clinically
      significant total scores (cutoff>15) for psychiatric symptoms, as defined by the
      CDI and RCMAS scoring scales, were reviewed. RESULTS: Nineteen patients had
      headaches and clinically significant total scores for psychiatric symptoms. The
      mean age at headache diagnosis was 11.7 years, and 57% were male. Mean duration
      of headache was 11.5 months. Two point eight percent of the patients were
      diagnosed with psychiatric disorders including major depression (1.7%),
      generalized anxiety disorder (1.1%), and bipolar disorder (0.1%). Four patients
      (0.6%) were diagnosed with attention deficit/hyperactivity disorder (ADHD). Total
      mean CDI and RCMAS scores of patients referred to the psychiatric clinic were
      18.8 and 22.2, respectively. There was no correlation between CDI or RCMAS total
      scores and headache frequency, duration, or severity. CONCLUSION: We recommend
      that all patients with headache should be screened for depression and anxiety by
      CDI and RCMAS scores.

PMID- 25774199
TI  - Development of multifocal nodular lesions of a liver mimicking hepatic
      metastasis, following resection of an insulinoma in a child.
AB  - Insulinoma, which arises from insulin-producing pancreatic beta cells, is a rare
      tumor in children. Only 5%-10% of insulinomas are malignant and undergo
      metastasis. We report a case of an 11-year-old girl who experienced hypoglycemia
      related seizures induced by an insulinoma; after resection of the primary tumor,
      she developed hepatic focal nodular hyperplasia (FNH). Laboratory test results
      indicated marked hypoglycemia with hyperinsulinemia. Abdominal ultrasonography
      (US) and computed tomography results were normal; however, magnetic resonance
      imaging (MRI) showed a solid mass in the pancreatic tail. Therefore, laparoscopic
      distal pancreatectomy was performed. Two months after the surgery, an abdominal
      MRI revealed multiple nodular lesions in the liver. An US-guided liver biopsy was
      then performed, and histological examination revealed FNH without necrosis or
      mitotic activity. The patient has been free of hypoglycemia for 2 years, and
      recent MRI studies showed a decrease in the size of FNH lesions, without any
      evidence of metastasis. Even though no metastatic lesions are noted on imaging,
      close observation and follow-up imaging studies are required in a child with
      insulinoma that has malignant potential on histopathologic findings. 

PMID- 25774200
TI  - New daily persistent headache with isolated sphenoiditis in children.
AB  - Isolated sphenoid sinusitis is a rare disease in children, and its symptoms are
      often nonspecific and confusing. Rarely, severe headache can be the first or only
      symptom of isolated sphenoid sinusitis. New daily persistent headache (NDPH) is a
      form of chronic daily headache that may have features of both migraines and
      tension-type headaches. NDPH is difficult to diagnose and requires a multifaceted
      approach. Here, we report on a 10-year-old boy and an 11-year-old girl who both
      presented with typical NDPH symptoms. These patients had no nasal symptoms or
      signs of infection. Neither nonsteroidal anti-inflammatory drugs nor topiramate
      had any effect on the headaches. Their neurological and ophthalmological
      examinations were normal. The results of routine blood work, including thyroid
      function tests, inflammatory markers, complete blood count, tests for viral
      infection, and a metabolic panel, were normal. A brain magnetic resonance imaging
      scan showed isolated sphenoid sinusitis. Both patients' symptoms resolved
      completely after approximately 1 month of oral antibiotics for sinusitis. 

PMID- 25774202
TI  - AMP-activated protein kinase is required for the anti-adipogenic effects of alpha
      linolenic acid.
AB  - BACKGROUND: n-3 long chain polyunsaturated fatty acid (n-3 LC PUFA) increases
      beta-oxidation and limits lipid accumulation in adipocytes. The current study was
      conducted to determine whether their precursor alpha-linolenic acid (ALA) could
      also exert the above effects and how AMP-activated protein kinase (AMPK) was
      involved. METHODS: AMPKalpha1(-/-), AMPKalpha2(-/-) mice and wild-type (WT) mice
      were fed a high-fat diet (HFD) or HFD with ALA. Body weight was recorded weekly
      and serum was collected. Adipocytes size and expression of key players involved
      in mitochondrial biogenesis and lipid oxidation were also measured. RESULTS: Our
      results showed an elevated serum adiponectin level and a decreased leptin and
      insulin level in WT mice fed HFD with ALA when compared with WT mice fed HFD. In
      addition, dietary ALA decreased epididymal adiposity and adipocytes size in WT
      mice. At protein level, mitochondrial genes (peroxisome proliferator-activated
      receptor gamma coactivator 1 alpha [PGC1alpha] and nuclear respiratory factor-1
      [nrf1]) and beta-oxidation related genes (carnitine palmitoyltransferase 1A
      [CPT1a] and peroxisome proliferator-activated receptor alpha [PPARalpha]) were
      upregulated by dietary ALA in epididymal fat of WT mice. Consistently, dietary
      ALA also increased mitochondrial genomic DNA copy numbers. Moreover, lipogenesis
      was repressed by dietary ALA, indicated by that expression of fatty acid synthase
      (FAS), acetyl CoA carboxylase (ACC) and stearoyl-CoA desaturase 1 (SCD1) were
      decreased. However, these aforementioned effects were abolished in the AMPKalpha1
      and AMPKalpha2 knockout mice. CONCLUSIONS: Our results suggest that ALA could
      improve adipose tissue function and its anti-adipogenic effects are dependent on
      AMPK.

PMID- 25774203
TI  - Inhibition of TGF-beta by a novel PPAR-gamma agonist, chrysin, salvages beta
      receptor stimulated myocardial injury in rats through MAPKs-dependent mechanism.
AB  - BACKGROUND: Pharmacological stimulation of peroxisome proliferator-activated
      receptor-gamma (PPAR-gamma) has been recognized as a molecular switch in
      alleviating myocardial injury through modulating oxidative, inflammatory and
      apoptotic signaling pathways. This study was designed to elucidate the effect of
      chrysin, a novel PPAR-gamma agonist and its functional interaction with TGF
      beta/MAPKs in isoproterenol-challenged myocardial injury in rats. METHODS: Male
      Wistar Albino rats were either subjected to vehicle (1.5 mL/kg, p.o.) or chrysin
      (15-60 mg/kg, p.o.) for 28 days. Isoproterenol (85 mg/kg, s.c.) was administered
      to rats on 27(th) and 28(th) day to induce myocardial injury. RESULTS: Chrysin
      dose dependently improved ventricular (+/-LVdP/dtmax and LVEDP) and hemodynamic
      (SAP, MAP and DAP) dysfunction in isoproterenol-insulted rats. This beneficial
      effect of chrysin was well supported with increased expression of PPAR-gamma and
      decreased expression of TGF-beta as evidenced by western blotting and
      immunohistochemistry analysis. Moreover, downstream signaling pathway of TGF-beta
      viz. P-ERK1/2/ERK1/2 activation and P-JNK/JNK, P-p38/p38 and MMP-2 inhibition
      were also observed. Chrysin also attenuated NF-kappaBp65 and IKK-beta
      expressions, TNF-alpha level and TUNEL positivity thereby validating its anti
      inflammatory and anti-apoptotic properties. Additionally, chrysin in a dose
      dependent fashion improved NO level, redox status of the myocardium (GSH and MDA
      levels and SOD, GSHPx and CAT activities), cardiac injury markers (CK-MB and LDH
      levels) and oxidative DNA damage marker (8-OHdG level) and displayed preservation
      of subcellular and ultrastructural components. CONCLUSION: We established that
      activation of PPAR-gamma and inhibition of TGF-beta via MAPKs dependent mechanism
      is critical for cardioprotective effect of chrysin.

PMID- 25774201
TI  - How do high glycemic load diets influence coronary heart disease?
AB  - BACKGROUND: Diet has a significant relationship with the risk of coronary heart
      disease (CHD). Traditionally the effect of diet on CHD was measured with the
      biomarker for low-density lipoprotein (LDL) cholesterol. However, LDL is not the
      only or even the most important biomarker for CHD risk. A suitably integrated
      view of the mechanism by which diet influences the detailed CHD pathogenetic
      pathways is therefore needed in order to better understand CHD risk factors and
      help with better holistic CHD prevention and treatment decisions. METHODS: A
      systematic review of the existing literature was conducted. From this an
      integrated CHD pathogenetic pathway system was constructed. CHD biomarkers, which
      are found on these pathways, are the only measurable data to link diet with these
      CHD pathways. They were thus used to simplify the link between diet and the CHD
      mechanism. Data were systematically analysed from 294 cohort studies of CHD
      biomarkers constituting 1 187 350 patients. RESULTS AND DISCUSSION: The resulting
      integrated analysis provides insight into the higher-order interactions
      underlying CHD and high-glycemic load (HGL) diets. A novel "connection graph"
      illustrates the measurable relationship between HGL diets and the relative risks
      attributed to the important CHD serological biomarkers. The "connection graph"
      vividly shows that HGL diets not only influence the lipid and metabolic
      biomarkers, but also the inflammation, coagulation and vascular function
      biomarkers in an important way. CONCLUSION: A focus primarily on the low density
      lipoprotein cholesterol biomarker for CHD risk has led to the traditional
      guidelines of CHD dietary recommendations. This has however inadvertently led to
      HGL diets. The influence of HGL diets on the other CHD biomarkers is not always
      fully appreciated. Thus, new diets or other interventions which address the full
      integrated CHD impact, as shown in this paper, are required.

PMID- 25774204
TI  - An ontology approach to comparative phenomics in plants.
AB  - BACKGROUND: Plant phenotype datasets include many different types of data,
      formats, and terms from specialized vocabularies. Because these datasets were
      designed for different audiences, they frequently contain language and details
      tailored to investigators with different research objectives and backgrounds.
      Although phenotype comparisons across datasets have long been possible on a small
      scale, comprehensive queries and analyses that span a broad set of reference
      species, research disciplines, and knowledge domains continue to be severely
      limited by the absence of a common semantic framework. RESULTS: We developed a
      workflow to curate and standardize existing phenotype datasets for six plant
      species, encompassing both model species and crop plants with established genetic
      resources. Our effort focused on mutant phenotypes associated with genes of known
      sequence in Arabidopsis thaliana (L.) Heynh. (Arabidopsis), Zea mays L. subsp.
      mays (maize), Medicago truncatula Gaertn. (barrel medic or Medicago), Oryza
      sativa L. (rice), Glycine max (L.) Merr. (soybean), and Solanum lycopersicum L.
      (tomato). We applied the same ontologies, annotation standards, formats, and best
      practices across all six species, thereby ensuring that the shared dataset could
      be used for cross-species querying and semantic similarity analyses. Curated
      phenotypes were first converted into a common format using taxonomically broad
      ontologies such as the Plant Ontology, Gene Ontology, and Phenotype and Trait
      Ontology. We then compared ontology-based phenotypic descriptions with an
      existing classification system for plant phenotypes and evaluated our semantic
      similarity dataset for its ability to enhance predictions of gene families,
      protein functions, and shared metabolic pathways that underlie informative plant
      phenotypes. CONCLUSIONS: The use of ontologies, annotation standards, shared
      formats, and best practices for cross-taxon phenotype data analyses represents a
      novel approach to plant phenomics that enhances the utility of model genetic
      organisms and can be readily applied to species with fewer genetic resources and
      less well-characterized genomes. In addition, these tools should enhance future
      efforts to explore the relationships among phenotypic similarity, gene function,
      and sequence similarity in plants, and to make genotype-to-phenotype predictions
      relevant to plant biology, crop improvement, and potentially even human health.

PMID- 25774205
TI  - The leaf angle distribution of natural plant populations: assessing the canopy
      with a novel software tool.
AB  - BACKGROUND: Three-dimensional canopies form complex architectures with temporally
      and spatially changing leaf orientations. Variations in canopy structure are
      linked to canopy function and they occur within the scope of genetic variability
      as well as a reaction to environmental factors like light, water and nutrient
      supply, and stress. An important key measure to characterize these structural
      properties is the leaf angle distribution, which in turn requires knowledge on
      the 3-dimensional single leaf surface. Despite a large number of 3-d sensors and
      methods only a few systems are applicable for fast and routine measurements in
      plants and natural canopies. A suitable approach is stereo imaging, which
      combines depth and color information that allows for easy segmentation of green
      leaf material and the extraction of plant traits, such as leaf angle
      distribution. RESULTS: We developed a software package, which provides tools for
      the quantification of leaf surface properties within natural canopies via 3-d
      reconstruction from stereo images. Our approach includes a semi-automatic
      selection process of single leaves and different modes of surface
      characterization via polygon smoothing or surface model fitting. Based on the
      resulting surface meshes leaf angle statistics are computed on the whole-leaf
      level or from local derivations. We include a case study to demonstrate the
      functionality of our software. 48 images of small sugar beet populations (4
      varieties) have been analyzed on the base of their leaf angle distribution in
      order to investigate seasonal, genotypic and fertilization effects on leaf angle
      distributions. We could show that leaf angle distributions change during the
      course of the season with all varieties having a comparable development.
      Additionally, different varieties had different leaf angle orientation that could
      be separated in principle component analysis. In contrast nitrogen treatment had
      no effect on leaf angles. CONCLUSIONS: We show that a stereo imaging setup
      together with the appropriate image processing tools is capable of retrieving the
      geometric leaf surface properties of plants and canopies. Our software package
      provides whole-leaf statistics but also a local estimation of leaf angles, which
      may have great potential to better understand and quantify structural canopy
      traits for guided breeding and optimized crop management.

PMID- 25774206
TI  - Two-dimensional multifractal detrended fluctuation analysis for plant
      identification.
AB  - BACKGROUND: In this paper, a novel method is proposed to identify plant species
      by using the two- dimensional multifractal detrended fluctuation analysis (2D MF
      DFA). Our method involves calculating a set of multifractal parameters that
      characterize the texture features of each plant leaf image. An index, I 0, that
      characterizes the relation of the intra-species variances and inter-species
      variances is introduced. This index is used to select three multifractal
      parameters for the identification process. The procedure is applied to the
      Swedish leaf data set containing leaves from fifteen different tree species.
      RESULTS: The chosen three parameters form a three-dimensional space in which the
      samples from the same species can be clustered together and be separated from
      other species. Support vector machines and kernel methods are employed to assess
      the identification accuracy. The resulting averaged discriminant accuracy reaches
      98.4% for every two species by the 10 - fold cross validation, while the accuracy
      reaches 93.96% for all fifteen species. CONCLUSIONS: Our method, based on the 2D
      MF-DFA, provides a feasible and efficient procedure to identify plant species.

PMID- 25774207
TI  - Direct comparison of MRI and X-ray CT technologies for 3D imaging of root systems
      in soil: potential and challenges for root trait quantification.
AB  - BACKGROUND: Roots are vital to plants for soil exploration and uptake of water
      and nutrients. Root performance is critical for growth and yield of plants, in
      particular when resources are limited. Since roots develop in strong interaction
      with the soil matrix, tools are required that can visualize and quantify root
      growth in opaque soil at best in 3D. Two modalities that are suited for such
      investigations are X-ray Computed Tomography (CT) and Magnetic Resonance Imaging
      (MRI). Due to the different physical principles they are based on, these
      modalities have their specific potentials and challenges for root phenotyping. We
      compared the two methods by imaging the same root systems grown in 3 different
      pot sizes with inner diameters of 34 mm, 56 mm or 81 mm. RESULTS: Both methods
      successfully visualized roots of two weeks old bean plants in all three pot
      sizes. Similar root images and almost the same root length were obtained for
      roots grown in the small pot, while more root details showed up in the CT images
      compared to MRI. For the medium sized pot, MRI showed more roots and higher root
      lengths whereas at some spots thin roots were only found by CT and the high water
      content apparently affected CT more than MRI. For the large pot, MRI detected
      much more roots including some laterals than CT. CONCLUSIONS: Both techniques
      performed equally well for pots with small diameters which are best suited to
      monitor root development of seedlings. To investigate specific root details or
      finely graduated root diameters of thin roots, CT was advantageous as it provided
      the higher spatial resolution. For larger pot diameters, MRI delivered higher
      fractions of the root systems than CT, most likely because of the strong root-to
      soil contrast achievable by MRI. Since complementary information can be gathered
      with CT and MRI, a combination of the two modalities could open a whole range of
      additional possibilities like analysis of root system traits in different soil
      structures or under varying soil moisture.

PMID- 25774208
TI  - Mathematical modeling of positron emission tomography (PET) data to assess
      radiofluoride transport in living plants following petiolar administration.
AB  - BACKGROUND: Ion transport is a fundamental physiological process that can be
      studied non-invasively in living plants with radiotracer imaging methods.
      Fluoride is a known phytotoxic pollutant and understanding its transport in
      plants after leaf absorption is of interest to those in agricultural areas near
      industrial sources of airborne fluoride. Here we report the novel use of a
      commercial, high-resolution, animal positron emission tomography (PET) scanner to
      trace a bolus of [(18)F]fluoride administered via bisected petioles of Brassica
      oleracea, an established model species, to simulate whole plant uptake of
      atmospheric fluoride. This methodology allows for the first time mathematical
      compartmental modeling of fluoride transport in the living plant. Radiotracer
      kinetics in the stem were described with a single-parameter free- and trapped
      compartment model and mean arrival times at different stem positions were
      calculated from the free-compartment time-activity curves. RESULTS: After
      initiation of administration at the bisected leaf stalk, [(18)F] radioactivity
      climbed for approximately 10 minutes followed by rapid washout from the stem and
      equilibration within leaves. Kinetic modeling of transport in the stem yielded a
      trapping rate of 1.5 +/- 0.3%/min (mean +/- s.d., n = 3), velocity of 2.2 +/- 1.1
      cm/min, and trapping fraction of 0.8 +/- 0.5%/cm. CONCLUSION: Quantitative
      assessment of physiologically meaningful transport parameters of fluoride in
      living plants is possible using standard positron emission tomography in
      combination with petiolar radiotracer administration. Movement of free fluoride
      was observed to be consistent with bulk flow in xylem, namely a rapid and linear
      change in position with respect to time. Trapping, likely in the apoplast, was
      observed. Future applications of the methods described here include studies of
      transport of other ions and molecules of interest in plant physiology.

PMID- 25774209
TI  - Sigmoid volvulus and ileo-sigmoid knotting: a five-year experience at a tertiary
      care hospital in Tanzania.
AB  - BACKGROUND: Sigmoid volvulus is a common cause of intestinal obstruction in
      developing countries where it affects relatively young people compared to
      developed countries. No prospective study has been done on this subject in
      Tanzania and Bugando Medical Centre in particular. This study describes in our
      region, the clinical presentation, management and outcome of sigmoid volvulus.
      METHODS: This was a descriptive prospective study of patients operated for
      sigmoid volvulus at Bugando Medical Centre from March 2009 to February 2014.
      RESULTS: A total of 146 patients (M: F = 5.1: 1) representing 14.2% of all cases
      of bowel obstruction were studied. The median age at presentation was 48 years.
      The disease significantly affected the older males compared with females (P =
      0.012). The majority of the patients 102, (93.2%) presented acutely and had to
      undergo emergency surgical intervention, the rest were either sub-acute or
      chronic. Out of the 146 patients studied, 24 (16.4%) had ileo-sigmoid knotting.
      The majority of patients, 102(69.9%) were treated with resection and primary
      anastomosis, of which 63.0% were emergency cases. Colostomy was offered to 30.1%
      of cases. No patient had sigmoidoscopic derotation. Complications mainly surgical
      site infections were reported in 20.5% of cases. The overall median length of
      hospital stay was 14 days. Overall mortality rate was 17.1%. The main predictors
      of mortality were advanced age (>60 years), concomitant medical illness, late
      presentation (>=24 hours), presence of shock on admission and presence of
      gangrenous bowel (P < 0.001). The follow up of patients in this study was
      generally poor as more than half of patients were lost to follow up. CONCLUSION:
      Sigmoid volvulus is not uncommon in our setting and commonly affects males than
      females. Most of the patients presented acutely, requiring immediate
      resuscitation and surgical approach. Findings from this study suggest that in
      viable bowel, sigmoid resection and primary anastomosis is feasible as it may not
      adversely affect outcome. Temporary colostomy should be considered if the bowel
      is gangrenous or perforated. Early diagnosis and timely definitive treatment are
      essential in order to decrease the morbidity and mortality associated with this
      disease.

PMID- 25774210
TI  - Non-invasive hemodynamic monitoring in trauma patients.
AB  - BACKGROUND: The assessment of hemodynamic status is a crucial task in the initial
      evaluation of trauma patients. However, blood pressure and heart rate are often
      misleading, as multiple variables may impact these conventional parameters. More
      reliable methods such as pulmonary artery thermodilution for cardiac output
      measuring would be necessary, but its applicability in the Emergency Department
      is questionable due to their invasive nature. Non-invasive cardiac output
      monitoring devices may be a feasible alternative. METHODS: A systematic
      literature review was conducted. Only studies that explicitly investigated non
      invasive hemodynamic monitoring devices in trauma patients were considered.
      RESULTS: A total of 7 studies were identified as suitable and were included into
      this review. These studies evaluated in a total of 1,197 trauma patients the
      accuracy of non-invasive hemodynamic monitoring devices by comparing measurements
      to pulmonary artery thermodilution, which is the gold standard for cardiac output
      measuring. The correlation coefficients r between the two methods ranged from
      0.79 to 0.92. Bias and precision analysis ranged from -0.02 +/- 0.78 l/min/m(2)
      to -0.14 +/- 0.73 l/min/m(2). Additionally, data on practicality, limitations and
      clinical impact of the devices were collected. CONCLUSION: The accuracy of non
      invasive cardiac output monitoring devices in trauma patients is broadly
      satisfactory. As the devices can be applied very early in the shock room or even
      preclinically, hemodynamic shock may be recognized much earlier and therapeutic
      interventions could be applied more rapidly and more adequately. The devices can
      be used in the daily routine of a busy ED, as they are non-invasive and easy to
      master.

PMID- 25774211
TI  - Non-heparinized ECMO serves a rescue method in a multitrauma patient combining
      pulmonary contusion and nonoperative internal bleeding: a case report and
      literature review.
AB  - Pulmonary contusion and acute respiratory distress syndrome (ARDS) is a common
      manifestation in polytraumatic patients. Although mechanical ventilation is still
      the first choice of treatment, a group of patients are still unable to maintain
      their oxygenation. The role of extracorporeal membrane oxygenation (ECMO) has
      been more clarified when the lung is extensively damaged and when conventional
      modality failed. ECMO provides the lung an opportunity to rest by permitting
      reduced ventilator settings and limiting further barotraumas. However, ECMO is
      still considered contraindicated in polytramatic patients combining pulmonary
      contusion and other organ hemorrhage because of systemic anticoagulation during
      the treatment. We herein report a patient who successfully survive a multitrauma
      combining pulmonary contusion and grade IV liver laceration using non-heparinized
      venovenous extracorporeal membrane oxygenation (vv-ECMO). The associated
      literature were reviewed. 

PMID- 25774212
TI  - Iatrogenic ureteric injuries following abdomino-pelvic operations: a 10-year
      tertiary care hospital experience in Tanzania.
AB  - BACKGROUND: Iatrogenic ureteric injuries are rare complications of abdomino
      pelvic surgery but associated with high morbidity and even mortality. There is
      paucity of data regarding iatrogenic ureteric injuries in Tanzania and Bugando
      Medical Centre in particular. This study describes our experience in the
      management and outcome of ureteric injuries following abdomino-pelvic operations
      outlining the causes, clinical presentation and outcome of management of this
      condition in our local setting. METHODS: This was a retrospective descriptive
      study of patients with iatrogenic ureteric injuries following abdomino-pelvic
      operations that were managed in Bugando Medical Centre between July 2004 and June
      2014. RESULTS: A total of 164 patients (M: F = 1: 1.6) were studied. Of these,
      154 (93.9%) were referred to Bugando Medical Centre having had their initial
      surgeries performed at other hospitals, whereas 10 (6.1%) patients sustained
      ureteric injuries during abdomino-pelvic surgery at Bugando Medical Centre. The
      median age at presentation was 36 years. The most common cause of iatrogenic
      ureteric injuries was total abdominal hysterectomy occurring in 69.2% of cases.
      The distal ureter was more frequently injured in 75.6% of cases. Suture ligation
      was the commonest type of injury accounting for 36.6% of patients. One hundred
      and sixteen (70.7%) patients had delayed diagnosis but underwent immediate
      repair. Ureteroneocystostomy was the most frequent reconstructive surgery
      performed in 58.0% of cases. Of the 164 patients, 152 (92.7%) were treated
      successfully. Twelve (7.3%) patients died in hospital. The main predictors of
      deaths were delayed presentation, deranged renal function tests on admission,
      missed ureteric injuries and surgical site infections (P < 0.001). The overall
      median length of hospital stay was 12 days. Follow up of patients was generally
      poor as more than half of patients were lost to follow up. CONCLUSION: Total
      abdominal hysterectomy still accounts for most cases of iatrogenic ureteric
      injuries in our environment. Meticulous surgical technique as well as
      identification of the course of the ureter and associated anatomic locations
      where injury is most likely to occur is important to decrease the risk of
      ureteric injury. Timely recognition of ureteric injury and its management is
      associated with good outcome.

PMID- 25774213
TI  - The Costs and Benefits of Development: The Transition From Crawling to Walking.
AB  - The transition from crawling to walking requires infants to relinquish their
      status as experienced, highly skilled crawlers in favor of being inexperienced,
      lowskilled walkers. Yet infants willingly undergo this developmental transition,
      despite incurring costs of shaky steps, frequent falls, and inability to gauge
      affordances for action in their new upright posture. Why do infants persist with
      walking when crawling serves the purpose of independent mobility? In this
      article, we present an integrative analysis of the costs and benefits associated
      with crawling and walking that challenges prior assumptions, and reveals deficits
      of crawling and benefits of upright locomotion that were previously overlooked.
      Inquiry into multiple domains of development reveals that the benefits of
      persisting with walking outweigh the costs: Compared to crawlers, walking infants
      cover more space more quickly, experience richer visual input, access and play
      more with distant objects, and interact in qualitatively new ways with
      caregivers.

PMID- 25774214
TI  - The relationship of motor skills and adaptive behavior skills in young children
      with autism spectrum disorders.
AB  - OBJECTIVE: To determine the relationship of motor skills and the core behaviors
      of young children with autism, social affective skills and repetitive behaviors,
      as indicated through the calibrated autism severity scores. DESIGN: The
      univariate GLM tested the relationship of gross and fine motor skills measured by
      the gross motor scale and the fine motor scale of the MSEL with autism
      symptomology as measured by calibrated autism severity scores. SETTING: Majority
      of the data collected took place in an autism clinic. PARTICIPANTS: A cohort of
      159 young children with ASD (n=110), PDD-NOS (n=26) and non-ASD (developmental
      delay, n=23) between the ages of 12-33 months were recruited from early
      intervention studies and clinical referrals. Children with non-ASD (developmental
      delay) were included in this study to provide a range of scores indicted through
      calibrated autism severity. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES:
      The primary outcome measures in this study were calibrated autism severity
      scores. RESULTS: Fine motor skills and gross motor skills significantly predicted
      calibrated autism severity (p < 0.01). Children with weaker motor skills
      displayed higher levels of calibrated autism severity. CONCLUSIONS: The fine and
      gross motor skills are significantly related to autism symptomology. There is
      more to focus on and new avenues to explore in the realm of discovering how to
      implement early intervention and rehabilitation for young children with autism
      and motor skills need to be a part of the discussion.

PMID- 25774215
TI  - A qualitative exploration of the perspectives of mental health professionals on
      stigma and discrimination of mental illness in Malaysia.
AB  - BACKGROUND: Stigma of mental illness has been identified as a significant barrier
      to help-seeking and care. Basic knowledge of mental illness - such as its nature,
      symptoms and impact - are neglected, leaving room for misunderstandings on mental
      health and 'stigma'. Numerous researches have been conducted on stigma and
      discrimination of people with mental disorders. However, most of the literature
      investigates stigma from a cultural conception point of view, experiences of
      patients or public attitudes towards mental illness but little to none from the
      standpoint of mental health professionals. In Malaysia, this research on stigma
      is particularly limited. Therefore, the state of stigma and discrimination of
      people with mental illness was investigated from the perspectives of mental
      health professionals in Malaysia. METHODS: In-depth, face-to-face, semi
      structured interviews were conducted with 15 mental health professionals from
      both government and private sectors including psychiatrists, psychologists and
      counsellors. The interviews were approximately 45-minutes long. The data was
      subsequently analysed using the basic thematic approach. RESULTS: Seven principal
      themes, each with their own sub-themes, emerged from the analysis of 'stigma of
      mental illness' from mental health professionals' point of view, including: (1)
      main perpetrators, (2) types of mental illness carrying stigma, (3) demography
      and geography of stigma, (4) manifestations of stigma, (5) impacts of stigma, (6)
      causes of stigma and (7) proposed initiatives to tackle stigma. Stigma of mental
      illness is widespread in Malaysia. This is most evident amongst people suffering
      from conditions such as schizophrenia, bipolar disorder and depression. Stigma
      manifests itself most often in forms of labelling, rejection, social exclusion
      and in employment. Family, friends and workplace staff are reported to be the
      main perpetrators of discriminatory conducts. CONCLUSION: According to the
      perspectives of the mental health professionals, implications of stigma include
      patients being trapped in a vicious cycle of discrimination leading to
      detrimental consequences for the individual, their families, communities and
      society as a whole. There is a pressing need to address stigma of mental illness
      and its consequences, especially through raising awareness of mental health and
      wellbeing in Malaysia, as reported by the mental health professionals.

PMID- 25774216
TI  - Comprehensive SDG goal and targets for non-communicable diseases and mental
      health.
AB  - The negotiations on the SDG goals and targets, leading to the sustainable
      development Declaration in September 2015, are now in the final stages. Ensuring
      that people with mental disorders are not left behind in the global development
      program from 2015 to 2030 will require specific and explicit commitments and
      targets against which progress in mental health can be measured and reported. The
      arguments for inclusion of explicit mental health targets in the SDGs are
      compelling. The final negotiations on the SDG goals and targets will now
      determine whether people with mental illness and psychosocial disabilities will
      continue to be neglected or will benefit equitably from inclusion in the post
      2015 development program. 

PMID- 25774217
TI  - 2G ethanol from the whole sugarcane lignocellulosic biomass.
AB  - BACKGROUND: In the sugarcane industry, large amounts of lignocellulosic residues
      are generated, which includes bagasse, straw, and tops. The use of the whole
      sugarcane lignocellulosic biomass for the production of second-generation (2G)
      ethanol can be a potential alternative to contribute to the economic viability of
      this process. Here, we conducted a systematic comparative study of the use of the
      lignocellulosic residues from the whole sugarcane lignocellulosic biomass
      (bagasse, straw, and tops) from commercial sugarcane varieties for the production
      of 2G ethanol. In addition, the feasibility of using a mixture of these residues
      from a selected variety was also investigated. RESULTS: The materials were
      pretreated with dilute acid and hydrolyzed with a commercial enzymatic
      preparation, after which the hydrolysates were fermented using an industrial
      strain of Saccharomyces cerevisiae. The susceptibility to enzymatic
      saccharification was higher for the tops, followed by straw and bagasse.
      Interestingly, the fermentability of the hydrolysates showed a different profile,
      with straw achieving the highest ethanol yields, followed by tops and bagasse.
      Using a mixture of the different sugarcane parts (bagasse-straw-tops, 1:1:1, in a
      dry-weight basis), it was possible to achieve a 55% higher enzymatic conversion
      and a 25% higher ethanol yield, compared to use of the bagasse alone. For the
      four commercial sugarcane varieties evaluated using the same experimental set of
      conditions, it was found that the variety of sugarcane was not a significant
      factor in the 2G ethanol production process. CONCLUSIONS: Assessment of use of
      the whole lignocellulosic sugarcane biomass clearly showed that 2G ethanol
      production could be significantly improved by the combined use of bagasse, straw,
      and tops, when compared to the use of bagasse alone. The lower susceptibility to
      saccharification of sugarcane bagasse, as well as the lower fermentability of its
      hydrolysates, can be compensated by using it in combination with straw and tops
      (sugarcane trash). Furthermore, given that the variety was not a significant
      factor for the 2G ethanol production process within the four commercial sugarcane
      varieties evaluated here, agronomic features such as higher productivity and
      tolerance of soil and climate variations can be used as the criteria for variety
      selection.

PMID- 25774218
TI  - Erratum to: Thrombospondin 1 is a key mediator of transforming growth factor b
      mediated cell contractility in systemic sclerosis via a mitogen-activated protein
      kinase kinase (MEK)/extracellular signal-regulated kinase (ERK)-dependent
      mechanism.
AB  - [This corrects the article DOI: 10.1186/1755-1536-4-9.]. 

PMID- 25774219
TI  - Partial trisomy 2q33.3-q37.3 in a patient with an inverted duplicated neocentric
      marker chromosome.
AB  - BACKGROUND: Increasing number of cases with small supernumerary marker
      chromosomes (sSMCs) without centromeric DNA and dozens of cases with trisomy 2q3
      have been reported in recent years. However, cases of simultaneous sSMC and
      partial trisomy of chromosome 2q have been rarely described. RESULTS: We report
      the case of a young girl patient with growth retardation and mild facial features
      due to a partial trisomy 2q33.3-37.3. The 34.3 Mb-duplication of the 2q33.3 to
      q37.3 region found in the patient constituted a supernumerary inverted duplicated
      neocentric marker chromosome. CONCLUSIONS: This is the first case of a patient
      with partial trisomy 2q33.3-37.3 presenting an inverted duplicated neocentric
      marker chromosome. Based on the case, this study will help further understanding
      the genotype/phenotype correlations of partial 2q3 duplication and exploring the
      relationship between neocentric sSMC and human diseases.

PMID- 25774220
TI  - Report of a patient and further clinical and molecular characterization of
      interstitial 4p16.3 microduplication.
AB  - BACKGROUND: Pure interstitial duplications of chromosome band 4p16.3 represent an
      infrequent chromosomal finding with, to the best of our knowledge, only two
      patients to date reported. CASE PRESENTATION: We report on a 13-year-old boy
      showing a set of dysmorphic facial features, attention deficit hyperactivity
      disorders, learning difficulties, speech and cognitive delays, overgrowth and
      musculoskeletal anomalies in whom an interstitial duplication of about 400 kb in
      4p16.3 was detected by SNP-array analysis. The duplication includes the complete
      coding sequence of FAM53A, SLBP, TMEM129 and TACC3 genes and the first exon of
      the FGFR3 gene. Phenotypic comparison with previously described patients
      harboring a microduplication of similar size and position contributes to better
      define the clinical correlation of 4p16.3 microduplications, suggesting the
      existence of a novel distinct and phenotypically recognizable syndrome. In
      addition, being the duplication identified in our case the smallest so far
      reported, it allowed us to refine the smallest region of overlap among patients
      to 222 kb, enabling a more accurate genotype-phenotype correlation for 4p16.3
      microduplications. CONCLUSIONS: Our case report provide clinical and molecular
      evidences supporting the existence of a novel 4p16.3 microduplication syndrome.
      The genes FAM53A, TACC3 and FGFR3 seems to play a key role in the etiology of the
      clinical phenotype. Interestingly, our patient is the oldest described so far and
      for this reason useful to delineate the long-term prognosis of these patients.

PMID- 25774221
TI  - Phenotypic variability in a Hungarian patient with the 4q21 microdeletion
      syndrome.
AB  - BACKGROUND: Interstitial deletions of 4q21 (MIM 613509) have already been
      reported in more than a dozen patients with deletions ranging from 2 to 15.1 Mb
      delineating a common phenotype including marked growth restriction, hypotonia,
      severe developmental delay with absent or delayed speech and distinctive facial
      features. A minimal critical region of 1.37 Mb accounting for the common features
      with 5 known genes (PRKG2, RASGEF1B, HNRNPD, HNRPDL, and ENOPH1) has been
      described so far. RESULTS: Here we report on a 5 year-old Hungarian girl
      presenting with severe developmental delay, good receptive language but absent
      spoken speech, short stature, dystrophy, hypotonia, distinctive facies including
      broad forehead, frontal bossing, downward slanting palpebral fissures,
      hypertelorism, hypoplastic ear-lobes, anteverted nostrils, short philtrum, small
      mouth, higharched palate, short, small hands and feet, distally narrowing fingers
      and clinodactyly. Cerebral MRI showed ventricular dilation and an increase in
      periventricular signal intensity. After extensive metabolic tests and exclusion
      of subtelomeric deletions array CGH analysis was performed using the Agilent
      Human Genome G3 SurePrint 8x60K Microarray (Agilent Technologies, USA), which
      detected a 4,85 Mb de novo interstitial deletion of 4q21.21-4q21.23. The clinical
      symptoms only partly overlap with reported 4q21 microdeletion cases. Among
      multiple annotated genes our patient is also haploinsufficient for the following
      genes: RASGEF1B being a strong candidate for the neurodevelopmental features and
      PRKG2 for severe growth delay. CONCLUSION: The first Hungarian case of 4q21
      deletion adds to the phenotypic spectrum of this novel microdeletion syndrome and
      underlines the importance of array CGH to uncover the heterogeneous causes of
      intellectual disability.

PMID- 25774222
TI  - Clinico-radiological and molecular characterization of a child with ring
      chromosome 2 presenting growth failure, microcephaly, kidney and brain
      malformations.
AB  - BACKGROUND: Ring chromosome 2 is a rare constitutional abnormality that generally
      occurs de novo. About 14 cases have been described to date, but the vast majority
      of papers report exclusively conventional cytogenetic investigations and only two
      have been characterized by array-CGH. RESULTS: Here we describe the clinical,
      neuroradiological, and molecular features of a 5-year-old boy harbouring a ring
      chromosome 2 presenting with severe growth failure, facial and bone dysmorphisms,
      microcephaly, and renal malformation. Brain MR with diffusion tensor imaging
      revealed simplified cortical gyration, pontine hypoplasia, and abnormally thick
      posterior corpus callosum, suggesting an underlying axonal guidance defect.
      Cytogenetic investigations showed a karyotype with a ring chromosome 2 and FISH
      analysis with subtelomeric probes revealed the absence of signals on both arms.
      These results were confirmed by array-CGH showing terminal deletions on 2p25.3
      (~439 kb) and 2q37.3 (~3.4 Mb). CONCLUSIONS: Our report describes a new patient
      with a ring chromosome 2 completely characterised by array-CGH providing
      additional information useful not only to study genotype-phenotype correlation
      but also to validate the role of already reported candidate genes and to suggest
      novel ones which could improve our understanding of the clinical features
      associated with ring chromosome 2.

PMID- 25774223
TI  - Parental Economic Hardship and Children's Achievement Orientations.
AB  - While children's orientations to achievement are strong predictors of
      attainments, little is known about how parental economic hardship during
      recessionary times influences children's orientations to their futures. The Youth
      Development Study has followed a community sample of young people in St Paul,
      Minnesota from mid-adolescence through their mid-thirties with near-annual
      surveys, and has recently begun surveying the children of this cohort. Using
      linked parent and child data, the present study examines the relationship between
      parental economic hardship and children's achievement orientations in the
      aftermath of the recent "Great Recession." Initial OLS analyses draw on 345
      parent-child pairs, with data collected from parents during their adolescence,
      during the decade prior to the recession, and in 2011, and from their children
      (age 11 and older) in 2011. Then, first difference models are estimated, based on
      a smaller sample (N=186) of parents and children who completed surveys in both
      2009 and 2011. Our findings indicate that when families are more vulnerable, as a
      result of low parental education and prior parental unemployment experience,
      children's achievement orientations are more strongly threatened by the family's
      economic circumstances. For example, as parental financial problems increased,
      economic expectations declined only among children of the least well-educated
      parents. Low household incomes diminished educational aspirations only when
      parents experienced unemployment during the ten years prior to the recent
      recession. Parental achievement orientations, as adolescents, were also found to
      moderate the impacts of shifts in the family's economic circumstances. Finally,
      boys reacted more strongly to their parents' hardship than girls.

PMID- 25774224
TI  - eTOXlab, an open source modeling framework for implementing predictive models in
      production environments.
AB  - BACKGROUND: Computational models based in Quantitative-Structure Activity
      Relationship (QSAR) methodologies are widely used tools for predicting the
      biological properties of new compounds. In many instances, such models are used
      as a routine in the industry (e.g. food, cosmetic or pharmaceutical industry) for
      the early assessment of the biological properties of new compounds. However, most
      of the tools currently available for developing QSAR models are not well suited
      for supporting the whole QSAR model life cycle in production environments.
      RESULTS: We have developed eTOXlab; an open source modeling framework designed to
      be used at the core of a self-contained virtual machine that can be easily
      deployed in production environments, providing predictions as web services.
      eTOXlab consists on a collection of object-oriented Python modules with methods
      mapping common tasks of standard modeling workflows. This framework allows
      building and validating QSAR models as well as predicting the properties of new
      compounds using either a command line interface or a graphic user interface
      (GUI). Simple models can be easily generated by setting a few parameters, while
      more complex models can be implemented by overriding pieces of the original
      source code. eTOXlab benefits from the object-oriented capabilities of Python for
      providing high flexibility: any model implemented using eTOXlab inherits the
      features implemented in the parent model, like common tools and services or the
      automatic exposure of the models as prediction web services. The particular
      eTOXlab architecture as a self-contained, portable prediction engine allows
      building models with confidential information within corporate facilities, which
      can be safely exported and used for prediction without disclosing the structures
      of the training series. CONCLUSIONS: The software presented here provides full
      support to the specific needs of users that want to develop, use and maintain
      predictive models in corporate environments. The technologies used by eTOXlab
      (web services, VM, object-oriented programming) provide an elegant solution to
      common practical issues; the system can be installed easily in heterogeneous
      environments and integrates well with other software. Moreover, the system
      provides a simple and safe solution for building models with confidential
      structures that can be shared without disclosing sensitive information.

PMID- 25774225
TI  - CPT1A: the future of heart disease detection and personalized medicine?

PMID- 25774226
TI  - Peripheral neuropathy is associated with insulin resistance independent of
      metabolic syndrome.
AB  - BACKGROUND: To determine the association of insulin resistance, metabolic
      syndrome (MetS) with peripheral neuropathy (PN). METHODS: This cross-sectional
      study consisted of 2035 subjects in Shanghai who were classified as with MetS and
      without MetS. The new International Diabetes Federation (IDF) criterion was used
      to define MetS. HOMA-IR was applied to evaluate insulin resistance. All subjects
      underwent complete foot examination. PN was assessed according to the neuropathy
      symptom and neuropathy disability scores. Binary logistic regression was
      performed to analyze the contributions of insulin resistance, features of MetS to
      PN. RESULTS: (1) The percentage of PN was 4.0% in our study. Patients with MetS
      (47.7%) had a higher percentage of PN (5.5% vs. 2.6%, respectively, P = 0.001).
      With the components of MetS increased (non-MetS, three, four, five), a linear
      increase in the proportion of peripheral neuropathy was observed (2.6%, 4.8%,
      5.6% and 7.2%; respectively, P for trend = 0.001). (2) In patients with PN, the
      average age of patients was significantly older than the corresponding non-PN
      patients. Waist circumference, fasting blood glucose, HbA1c, proportion of
      treatment for diabetes and hypertension were significantly higher in PN group
      compared with non-PN group in MetS patients. (3) The frequency of dysglycemia was
      the highest in PN patients both with and without MetS (96.2% and 82.1%, P =
      0.084). (4) After adjusting for gender and smoking history, the PN was associated
      with MetS [odds ratio (OR) 2.0; 95% confidence interval (CI) 1.2, 3.2; P =
      0.006], and age (OR 1.1; 95% CI 1.1, 1.1; P < 0.001). When HOMA-IR was added to
      this binary logistic regression, the association of PN with MetS disappeared (P =
      0.110), but the PN was still associated with HOMA-IR (OR 1.2; 95% CI 1.1, 1.4, P
      < 0.001). CONCLUSIONS: In metabolic syndrome, insulin resistance might play an
      important role in the development of peripheral neuropathy.

PMID- 25774227
TI  - Association between maternal glucose levels during pregnancy and gestational
      diabetes mellitus: an analytical cross-sectional study.
AB  - BACKGROUND: To evaluate the association between fasting glucose levels in women
      throughout pregnancy and the occurrence of gestational diabetes mellitus (GDM)
      and other pregnancy complications, macrosomia, and cesarean delivery. METHODS: An
      analytical cross-sectional study with 829 healthy pregnant women receiving health
      care at a public maternity unit in Rio de Janeiro between 1999 and 2008. The
      dependent variables assessed in the study were: GDM (was confirmed when two or
      more values were above the glucose curve using 100 g glucose), complications,
      mode of delivery and birth weight. Macrosomia was defined as a birth weight of
      >4000 g. The independent variables assessed were: maternal fasting glucose per
      trimester as a continuous variable, divided into three categories, socio
      demographic data on the mothers. The level of statistical significance was set at
      5%. RESULTS: The mean fasting glucose levels of the women who had GDM were higher
      in the second trimester than for those who had no pregnancy complications (90.5
      mg/dL vs. 78.5 mg/dL, p = 0.000). Higher mean fasting glucose levels were also
      found in the third trimester for women who developed GDM than for those with no
      pregnancy complications (90 mg/dL vs. 77.8 mg/dL, p = 0.016). Women who had a
      cesarean delivery had higher fasting glucose levels in the second (80.4 mg/dL vs.
      78 mg/dL, post hoc = 0.034) and third (80.4 mg/dL and 77.1 mg/dL; post hoc =
      0.005) trimesters than women who had a normal delivery. Also, higher fasting
      glucose levels were found in the second semester for women whose infants had
      macrosomia than for women whose newborns were normal weight (86.2 mg/dL and 78.8
      mg/dL; post hoc = 0.003). The chance of develop GDM was higher for the women with
      glucose levels in the 90-94 mg/dL range in the second trimester (OR = 7.2; 95% CI
      = 2.33-22.24) than for the women whose glucose levels were in the <80 mg/dL and
      80-90 mg/dL ranges. CONCLUSION: Second and third trimester fasting glucose levels
      below the cut-off values for the diagnosis of GDM are associated with an
      increased risk of pregnancy complications. The dependent variables assessed in
      the study were: GDM (present/absent), complications, mode of delivery (normal,
      forceps, cesarean), and birth weight.

PMID- 25774228
TI  - Erratum: Body composition study by dual-energy x-ray absorptiometry in familial
      partial lipodystrophy: finding new tools for an objective evaluation.
AB  - [This corrects the article DOI: 10.1186/1758-5996-4-40.]. 

PMID- 25774230
TI  - Contact-mediated intracellular delivery of hydrophobic drugs from polymeric
      nanoparticles.
AB  - Encapsulation of drugs in nanoparticles can enhance the accumulation of drugs in
      tumours, reduce toxicity toward healthy tissue, and improve pharmacokinetics
      compared to administration of free drug. To achieve efficient delivery and
      release of drugs at the target site, mechanisms of interaction between the
      nanoparticles and cells and the mechanism of delivery of the encapsulated drug
      are crucial to understand. Our aim was to determine the mechanisms for cellular
      uptake of a fluorescent hydrophobic model drug from poly(butylcyanoacrylate)
      nanoparticles. Prostate adenocarcinoma cells were incubated with Nile Red-loaded
      nanoparticles or free Nile Red. Uptake and intracellular distribution were
      evaluated by flow cytometry and confocal laser scanning microscopy. The
      nanoparticles mediated a higher intracellular level and more rapid uptake of
      encapsulated Nile Red compared to model drug administered alone. The main
      mechanism for delivery was not by endocytosis of nanoparticles but by
      nanoparticle-cell contact-mediated transfer directly to the cytosol and, to a
      smaller extent, release of payload from nanoparticles into the medium followed by
      diffusion into cells. The payload thus avoids entering the endocytic pathway,
      evading lysosomal degradation and instead gains direct access to intracellular
      targets. The nanoparticles are promising tools for efficient intracellular
      delivery of hydrophobic anticancer drugs; therefore, they are clinically relevant
      for improved cancer therapy.

PMID- 25774233
TI  - Significance of Incidental Nasopharyngeal Uptake on (18)F-FDG PET/CT: Patterns of
      Benign/Physiologic Uptake and Differentiation from Malignancy.
AB  - PURPOSE: The purpose of this study was to assess the significance of incidental
      nasopharyngeal uptake on 18F-FDG PET/CT and to identify image patterns useful in
      the differentiation between benign or physiologic activity and nasopharyngeal
      carcinoma. METHODS: We retrospectively reviewed medical records of patients with
      nasopharyngeal uptakes on 18F-FDG PET/CT scans taken between January 2010 and
      July 2011. Patients with head and neck cancer, other metastatic head and neck
      lesions, or lymphoma were excluded. Total 177 patients were enrolled (Group A).
      PET images were reviewed for patterns of nasopharyngeal FDG uptake,
      presence/absence of cervical lymph node uptake and pattern of cervical node
      uptake. Diagnostic confirmation was made by pathology or clinical and
      radiological follow-up for 1 year or longer. Furthermore, initial PET/CT images
      of 48 patients with nasopharyngeal carcinoma (Group B) were reviewed for
      comparison with PET/CT images of Group A patients. RESULTS: All nasopharyngeal
      uptakes in Group A were confirmed to be benign. Group B showed significantly more
      intense FDG uptake (SUVmax of Group A 3.9 +/- 1.4 vs. Group B 10.4 +/- 4.6,
      p<0.001). and asymmetric nasopharyngeal uptake (asymmetric uptake of Group A
      67.8% vs. Group B 89.6%). When SUVmax of 6.0 was used as cut off for detection of
      malignant nasopharyngeal uptake, the area under the ROC curve was 0.93 (95%
      confidence interval, 0.88-0.98), with a sensitivity of 88.1% and a specificity of
      91.7%. Metastatic nodes in Group B showed higher SUVmax (Group A 2.3 +/- 0.6 vs.
      Group B 7.1 +/- 4.0, p<0.001) and larger size (short axis of Group A 5.3 +/- 2.0
      mm vs. Group B 13.1 +/- 4.7 mm, p<0.001) than benign nodes of Group A. The
      majority of Group B cases demonstrated retropharyngeal lymph node uptake (70.8%),
      compared to only 2 cases in Group A. CONCLUSIONS: In patients without a history
      of underlying malignancy involving head and neck, incidental nasopharyngeal
      uptake on PET/CT does not indicate malignancy. However, if the nasopharyngeal
      uptake is intense (SUVmax>=6.0) or concomitant retropharyngeal lymph node uptake
      is present, the possibility of a malignant condition should be considered.

PMID- 25774232
TI  - In vivo cell tracking with bioluminescence imaging.
AB  - Molecular imaging is a fast growing biomedical research that allows the visual
      representation, characterization and quantification of biological processes at
      the cellular and subcellular levels within intact living organisms. In vivo
      tracking of cells is an indispensable technology for development and optimization
      of cell therapy for replacement or renewal of damaged or diseased tissue using
      transplanted cells, often autologous cells. With outstanding advantages of
      bioluminescence imaging, the imaging approach is most commonly applied for in
      vivo monitoring of transplanted stem cells or immune cells in order to assess
      viability of administered cells with therapeutic efficacy in preclinical small
      animal models. In this review, a general overview of bioluminescence is provided
      and recent updates of in vivo cell tracking using the bioluminescence signal are
      discussed. 

PMID- 25774234
TI  - Correlation of Primary Tumor FDG Uptake with Clinicopathologic Prognostic Factors
      in Invasive Ductal Carcinoma of the Breast.
AB  - PURPOSE: The purpose of this study was to investigate the correlation of primary
      tumor FDG uptake to clinicopathological prognostic factors in invasive ductal
      carcinoma of the breast. METHODS: We retrospectively reviewed 136 of 215 female
      patients with pathologically proven invasive ductal breast cancer from January
      2008 to December 2011 who underwent F-18 FDG PET/CT for initial staging and
      follow-up after curative treatment with analysis of estrogen receptor (ER),
      progesterone receptor (PR) and human epithelial growth factor receptor 2 (HER2).
      The maximum standardized uptake value (SUVmax) of the primary breast tumor was
      measured and compared with hormonal receptor and HER2 overexpression status.
      RESULTS: The high SUVmax of primary breast tumors is significantly correlated
      with the clinicopathological factors: tumor size, histologic grade, TNM stage,
      negativity of ER, negativity of PR, HER2 overexpression and triple negativity.
      The recurrent group with non-triple negative cancer had a higher SUVmax compared
      with the non-recurrent group, though no significant difference in FDG uptake was
      noted between the recurrence and non-recurrent groups in subjects with triple
      negative cancer. Lymph node involvement was the independent risk factor for
      cancer recurrence in the multivariate analysis. CONCLUSIONS: In conclusion, high
      FDG uptake in primary breast tumors is significantly correlated with
      clinicopathological factors, such as tumor size, histologic grade, TNM stage,
      negativity of the hormonal receptor, HER2 overexpression and triple negativity.
      Therefore, FDG PET/CT is a helpful prognostic tool to direct the further
      management of patients with breast cancer.

PMID- 25774235
TI  - The clinical value of hybrid sentinel lymphoscintigraphy to predict metastatic
      sentinel lymph nodes in breast cancer.
AB  - PURPOSE: Hybrid imaging techniques can provide functional and anatomical
      information about sentinel lymph nodes in breast cancer. Our aim in this study
      was to evaluate which imaging parameters on hybrid sentinel lymphoscintigraphy
      predicted metastatic involvement of sentinel lymph nodes (SLNs) in patients with
      breast cancer. METHODS: Among 56 patients who underwent conventional sentinel
      lymphoscintigraphy, 45 patients (age, 53.1 +/- 9.5 years) underwent hybrid
      sentinel lymphoscintigraphy using a single-photon emission computed tomography
      (SPECT)/computed tomography (CT) gamma camera. On hybrid SPECT/CT images, we
      compared the shape and size (long-to-short axis [L/S] ratio) of the SLN, and
      SLN/periareolar injection site (S/P) count ratio between metastatic and non
      metastatic SLNs. Metastatic involvement of sentinel lymph nodes was confirmed by
      pathological biopsy. RESULTS: Pathological biopsy revealed that 21 patients (46.7
      %) had metastatic SLNs, while 24 (53.3 %) had non-metastatic SLNs. In the 21
      patients with metastatic SLNs, the SLN was mostly round (57.1 %) or had an
      eccentric cortical rim (38.1 %). Of 24 patients with non-metastatic SLNs, 13
      patients (54.1 %) had an SLN with a C-shape rim or eccentric cortex. L/S ratio
      was 2.04 for metastatic SLNs and 2.38 for non-metastatic SLNs. Seven (33 %)
      patients had T1 primary tumors and 14 (66 %) had T2 primary tumors in the
      metastatic SLN group. In contrast, 18 (75 %) patients had T1 primary tumors and
      six (25 %) had T2 tumors in the non-metastatic SLN group. S/P count ratio was
      significantly lower in the metastatic SLN group than the non-metastatic SLN group
      for those patients with a T1 primary tumor (p = 0.007). CONCLUSIONS: Hybrid
      SPECT/CT offers the physiologic data of SPECT together with the anatomic data of
      CT in a single image. This hybrid imaging improved the anatomic localization of
      SLNs in breast cancer patients and predicted the metastatic involvement of SLNs
      in the subgroup of breast cancer patients with T1 primary tumors.

PMID- 25774236
TI  - The Role of (18)F-FDG PET/CT as a Prognostic Factor in Patients with Synovial
      Sarcoma.
AB  - PURPOSE: This research aims to investigate the potential of (18)F
      fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET) to
      predict pathologic response after neoadjuvant chemotherapy (NAC) and overall
      survival (OS) of patients with synovial sarcoma in Korea. METHODS: Twenty
      patients with synovial sarcoma from January 2001 to December 2011 were reviewed
      retrospectively. All patients underwent pre-treatment FDG PET and tumor removal.
      Patients were classified with the maximum SUV (SUVmax), metabolic tumor volume
      (MTV), total lesion glycolysis (TLG), age, sex, histologic subtype, tumor size,
      NAC, resection margin, and metastasis at diagnosis. Pathologic response was
      assessed using the French Federation of Cancer Centers system. Statistical
      analyses were analyzed using the Kaplan-Meier method, log-rank test, Cox
      proportional hazards regression model, and Mann-Whitney test. RESULTS: Nine
      patients (45 %) showed pathologic response, and ten patients survived. Higher
      SUVmax, higher MTV, higher TLG, monophasic epithelial type, and metastasis at
      diagnosis were significantly related to poorer OS (p = 0.047, 0.016, 0.016,
      0.045, and 0.018, respectively). By multivariate analysis, metastasis at
      diagnosis was significantly related to poorer OS (p = 0.012/HR = 5.9, 95 % CI
      1.47 to 24.1). The SUVmax, MTV, and TLG of the non-responder group were
      significantly higher than those of the responder group (p = 0.020, 0.020, and
      0.020, respectively). There was no significant difference in size between the two
      groups (p = 0.062). CONCLUSIONS: A higher SUVmax on the pre-treatment scan,
      monophasic epithelial type, and metastasis at diagnosis were significantly
      associated with a poorer OS, and pathologic responders showed a higher SUVmax
      before NAC. The PET parameters can be used to predict OS and pathologic response
      in patients with synovial sarcomas before NAC.

PMID- 25774237
TI  - Value of (18)F-FDG PET/CT in the Detection of Ovarian Malignancy.
AB  - PURPOSE: Ovarian cancer is a leading cause of gynecologic malignancy. As symptoms
      of ovarian cancer are nonspecific, only 20 % of ovarian cancers are diagnosed
      while they are still limited to the ovaries. Thus, early and accurate detection
      of disease is important for an improved prognosis. For the accurate and effective
      diagnosis of ovarian malignancy on (18)F-fluorodeoxyglucose ((18)F-FDG) positron
      emission tomography/computed tomography (PET/CT), we analyzed several parameters,
      including visual assessment. METHOD: A total of 51 peritoneal lesions in 19
      patients who showed ovarian masses with diffuse peritoneal infiltration were
      enrolled. Twelve patients were confirmed to have ovarian malignancy and seven
      patients with benign disease by pathologic examination. All patients were
      examined by (18)F-FDG PET/CT, and an additional 2-h delayed (18)F-FDG PET/CT was
      also performed for 15 patients with 42 peritoneal lesions. We measured
      semiquantitative parameters including maximum and mean standardized uptake values
      (SUVmax, SUVmean), metabolic tumor volume (MTV), and total lesion glycolysis
      (TLG) on a 1-h initial (18)F-FDG PET/CT image (Parameter1) and on a 2-h delayed
      image (Parameter2). Additionally, retention indices of each parameter were
      calculated, and each parameter among the malignant and benign lesions was
      compared by Mann-Whitney U test. We also assessed the visual characteristics of
      each peritoneal lesion, including metabolic extent, intensity, shape,
      heterogeneity, and total visual score. Associations between visual grades and
      malignancy were analyzed using linear by linear association methods. Moreover, a
      receiver operating characteristic (ROC) curve was analyzed to compare the
      effectiveness of significant parameters. RESULT: In a comparison between the
      malignant and benign groups in the analysis of 51 total peritoneal lesions,
      SUVmax1, SUVmean1, and TLG1 showed significant differences. Also, in the analysis
      of 42 peritoneal lesions that underwent an additional 2-h (18)F-FDG PET/CT
      examination, SUVmax1,2, SUVmean1,2, TLG2, and the RI of TLG showed significant
      differences between the malignant and benign groups. MTV did not show significant
      differences in either the analysis of 51 peritoneal lesions or of 42 lesions.
      Regarding visual assessments, metabolic intensity, shape, heterogeneity, and
      total visual score showed an association with malignancy. In the ROC analysis,
      the AUC of the visual score was larger than the AUC of other parameters in both
      the analyses of 51 peritoneal lesions and of 42 lesions. CONCLUSION: Although
      further study with a larger patient population is needed, the visual assessment
      of (18)F-FDG PET/CT imaging has a primary role in the detection of malignancy in
      ovarian cancer patients with assistance from other semi-quantitative parameters.

PMID- 25774238
TI  - Usefulness of (131)I-SPECT/CT and (18)F-FDG PET/CT in Evaluating Successful
      (131)I and Retinoic Acid Combined Therapy in a Patient with Metastatic Struma
      Ovarii.
AB  - Metastatic struma ovarii is an extremely rare disease, and the treatment of
      choice has not been established. Here, we introduce the case of a 36-year-old
      female pregnant patient with metastatic struma ovarii. Initial treatment was an
      exploratory laparotomy to remove multiple peritoneal masses. After delivery, a
      total thyroidectomy was done for the further (131)I-therapy. (131)I-SPECT/CT and
      (18) F-FDG PET/CT showed multiple hepatic metastases and extensive peritoneal
      seeding nodules. Multiple (131)I and retinoic acid combination therapies were
      performed, resulting in marked improvement. (131)I-SPECT/CT and (18) F-FDG PET/CT
      were quite useful for evaluating the biologic characteristics of the metastases. 

PMID- 25774239
TI  - Unilateral acute maculopathy associated with adult onset hand, foot and mouth
      disease: case report and review of literature.
AB  - BACKGROUND: Acute maculopathy is a rare condition of unknown aetiology and
      Coxsackie virus is known to be associated with this macular chorioretinitis.
      FINDINGS: We report a case of acute unilateral maculopathy in a 35-year-old woman
      with concurrent hand foot and mouth disease. Furthermore, we display multimodal
      imaging (colour fundus photographs, autofluorescence, spectral domain ocular
      coherence tomography, fluorescein angiography and indocyanine green angiography)
      charting the course of the disease. The source of the virus was thought to be the
      patient's child. Empirical treatment with oral corticosteroids was commenced and
      the inflammation resolved, leaving a residual macular scar. CONCLUSIONS: We
      present this case combined with the review of literature of adult onset Coxsackie
      virus-associated retinitis. This case reiterates the fact that Coxsackie virus is
      an uncommon but important consideration in the differential diagnosis of
      chorioretinitis and posterior uveitis with atypical retinopathy.

PMID- 25774240
TI  - Pulmonary benign metastasizing leiomyoma from the uterine leiomyoma: a case
      report.
AB  - BACKGROUND: Benign metastasizing leiomyoma (BML) is a rare condition described as
      multiple well-differentiated leiomyomas at sites distant from the uterus. Apart
      from lungs it has also been reported in lymph nodes, heart, brain, bone, skin,
      eye and spinal cord. We present a case of pulmonary benign metastasizing
      leiomyoma in a female patient admitted to our hospital with suspicion of left
      adnexal tumor. CASE REPORT: A 45-year-old woman was referred to our hospital with
      suspicion of left adnexal tumor. The control transvaginal ultrasound examination
      performed at admission to the Gynecological Department excluded adnexal neoplasm.
      However, a large amount of fluid within the Douglas pouch raised the oncological
      concern. The patient underwent myomectomy in 2005. In the same year she was
      diagnosed with multiple lung nodules and underwent pulmonary wedge resection with
      the diagnosis of pulmonary benign metastasizing leiomyoma being stated. The
      decision of reevaluation of the specimen, control CT and puncture of the Douglas
      pouch fluid was made. Computed tomography performed at the Department of
      Diagnostic Imaging and Interventional Radiology of the Pomeranian Medical
      University Hospital revealed multiple, bilateral nodules. The microscopic
      examination of the samples confirmed the initial diagnosis of benign
      metastasizing leiomyoma with no evidence of neoplastic cells within the fluid.
      CONCLUSIONS: Pulmonary benign metastasizing leiomyoma is a rare entity. However,
      it should be always taken into consideration in women with a previous or
      coincident history of uterine leiomyoma, especially when no evidence of other
      malignancy is present.

PMID- 25774241
TI  - Torsion of the greater omentum secondary to omental lymphangioma in a child: a
      case report.
AB  - BACKGROUND: Omental cyst and omental torsion both are uncommon but important
      causes of acute abdomen with a difficult clinical diagnosis due to nonspecific
      features. Here we report a case of an eight year old child with acute abdominal
      pain referred for USG and CT scan which revealed two cysts in greater omentum
      leading to secondary omental torsion. CASE REPORT: An eight year old male child
      presented to casualty with severe pain abdomen since 1 day. There was no history
      of vomiting or altered bowel habits. The patient was febrile with tachycardia on
      arrival. On examination rigidity and tenderness all over abdomen were present.
      Serum amylase was within normal range. USG and CECT abdomen were done
      subsequently. USG showed two well defined cystic lesions in lower abdomen with
      presence of some internal echogenic debris and calcified foci in their dependent
      part. There was also presence of omentum with a whirl of blood vessels seen along
      anterior abdominal wall leading to these lesions suggesting torsion. On colour
      Doppler the presence of blood flow within the whirl of vessels was seen. Mild
      amount of free fluid was also seen in the peritoneal cavity. On CECT abdomen the
      findings of omental cysts and torsion of greater omentum with free fluid in
      abdomen were confirmed. The cysts measured 60*55 and 65*55mm on CT. The patient
      was taken for an emergency laparotomy for indication of acute generalized
      peritonitis. Two large omental cysts were found in the pelvic cavity along with
      torsed greater omentum along with 150 ml of hemorrhagic fluid in peritoneal
      cavity. The cysts and twisted necrotic part of the greater omentum were excised
      at surgery. No postoperative complications were observed. Histopathologic
      examination was suggestive of lymphangioma of omentum. CONCLUSIONS: Lymphangioma
      of the omentum is an not very uncommon however acute presentation with omental
      torsion and infarction is an unusual entity. Optimal utilization of preoperative
      imaging with USG, Doppler and contrast enhanced CT scan can provide correct
      diagnosis.

PMID- 25774242
TI  - Does Blame Impede Health Recovery After Transport Accidents?
AB  - Blame towards the wrongdoer can be a source of distress for people who are
      injured in a transport accident. The association between blame and psychological
      stress is well investigated. In contrast, not much is known about blame and
      health-care utilization. It is important to investigate whether blame is
      associated with health-care consumption because it may contribute to our
      knowledge about what factors have an effect on recovery after transport
      accidents. The current study involved a total of 2940 participants, who were
      selected from a compensation database in Victoria, Australia. Health-care
      utilization, in general, and utilization of psychologist and physiotherapist
      visits, in particular, were defined as the outcome. In contrast to a previous
      study, it was found that blaming the other was associated with greater health
      care utilization, in general, and psychologists and physiotherapist visits,
      specifically. Another relevant finding was that, although the study involved a
      sample that was created to show an equal ratio of blame/no-blame, 61 % blamed the
      other driver; therefore, blame may be a motive to lodge a claim. Finally, we
      discuss the role that psychologists and claim managers could play in reducing
      feelings of blame in order to reduce health-care utilization and possibly improve
      recovery.

PMID- 25774243
TI  - Stereotactic body radiotherapy for early-stage non-small cell lung cancer:
      clinical outcomes from a National Patient Registry.
AB  - OBJECTIVES: Stereotactic body radiotherapy (SBRT) is a definitive local treatment
      option for patients with stage I non-small cell lung cancer (NSCLC) who are not
      surgical candidates and patients who refuse surgery. The purpose of this study
      was to assess the impact of SBRT on T1-T2 NSCLC from a national registry,
      reflecting practices and outcomes in a real-world setting. METHODS: The
      RSSearch(r) Patient Registry was screened for T1-T2N0M0 NSCLC patients treated
      from May 2004 to May 2013 with SBRT. Descriptive analyses were used for patient,
      tumor, and treatment characteristics. Overall survival (OS) and local control
      (LC) were calculated using the Kaplan-Meier method. RESULTS: In total, 723
      patients with 517 T1 and 224 T2 lesions were treated with SBRT. Median follow-up
      was 12 months (1-87 months) with a median age of 76 years. Median SBRT dose was
      54 Gy (range 10-80 Gy) delivered in a median of 3 fractions (range 1-5), and
      median biological equivalent dose (BED10) was 151.2 Gy (range 20-240 Gy). Median
      OS was 30 and 26 months for T1 and T2 tumors, respectively (p = 0.019). LC was
      associated with higher BED10 for T2 tumors, but not in T1 tumors at a median
      follow-up of 17 months. Seventeen-month LC for T2 tumors treated with BED10 < 105
      Gy, BED10 105-149, and BED10 >= 150 Gy was 43, 74, and 95 %, respectively (p =
      0.011). Local failure rates for T2 tumors treated with BED10 < 105 Gy, 105-149
      Gy, and >=150 Gy were 32, 21, and 8 % (p = 0.029), respectively. Median OS for
      patients with T2 tumors treated with BED10 < 105 Gy was 17 vs. 32 months for T2
      tumors treated with BED10 105-149 Gy (p = 0.062). CONCLUSION: SBRT for T1-T2
      NSCLC is feasible and effective in the community setting. OS was greater for
      patients with T1 lesions compared to T2 lesions. An improvement in LC was
      observed in patients with T2 lesions treated with BED10 > 105 Gy.

PMID- 25774244
TI  - Stereotactic body radiotherapy for re-irradiation of lung cancer recurrence with
      lower biological effective doses.
AB  - OBJECTIVE: Few studies have evaluated re-irradiation of lung cancer recurrences
      with stereotactic body radiotherapy (SBRT). This study evaluates outcomes with
      SBRT re-irradiation for recurrent lung cancer. METHODS: Two hundred and seventy
      eight patients treated with SBRT for lung cancer were retrospectively reviewed.
      Of those, 26 patients with 29 tumors were re-irradiated with SBRT. Ninety percent
      of tumors received prior external beam irradiation and 10 % received prior SBRT.
      Previous median radiation dose was 61.2 Gy with a median 8-month interval from
      previous radiation. The median re-irradiation SBRT dose was 30 Gy (48 Gy10
      biological effective dose (BED)). Endpoints evaluated included local control,
      overall survival, and progression-free survival. RESULTS: Twenty-five of 29
      tumors were evaluable for local control, with 27 tumors (93 %) considered in
      field recurrences. In-field crude local control rate was 80 % (20/25) with 1 and
      2-year actuarial rates of 78.6 and 65.5 %, respectively. One and 2-year actuarial
      survival rates were 52.3 and 37.0 %, respectively. One and 2-year actuarial
      progression-free survival rates were 56.7 and 37.0 %, respectively. Fifty-five
      percent of patients reported acute/chronic grades 1 and 2 toxicities. No grade 3
      or higher toxicities were reported. CONCLUSION: Patients with recurrent lung
      cancer have limited options. SBRT re-irradiation is tolerable even after a median
      61.2 Gy to the re-irradiation site. The lower BED used provided acceptable
      progression-free survival with low toxicity. Given the poor prognosis with
      current treatment options, new paradigms for re-treatment should include SBRT-re
      irradiation as an adjunct to systemic therapy for in-field lung cancer
      recurrence.

PMID- 25774245
TI  - Identification of possible factors influencing temperatures elevation during
      implant site preparation with piezoelectric technique.
AB  - BACKGROUND: Overheating during implant site preparation negatively affects the
      osseointegration process as well the final outcome of implant rehabilitations.
      Piezoelectric techniques seem to provide to a gentle implant preparation although
      few scientific reports have investigated the heat generation and its underlying
      factors. PURPOSE: To investigate, through a proper methodological approach, the
      main factors influencing temperature rise during piezoelectric implant site
      preparation. MATERIALS AND METHODS: Different piezoelectric tips (IM1s, IM2, P2
      3, IM3, Mectron Medical Technology, Carasco, Italy) have been tested. The
      experimental set-up consisted in a mechanical positioning device equipped with a
      load cell and a fluoroptic thermometer. RESULTS: The first tip of the sequence
      (IM1s) generated the highest temperature increasing (DeltaT). The diamond tips
      (IM1s and P2-3) determined higher DeltaT values than the smooth tips (IM2 and
      IM3). Further tests with IM1s suggested that the temperature elevation during the
      first thirty seconds may be predictive of the maximal temperature as well as of
      the overall thermal impact. CONCLUSIONS: Working load, working movements
      management and bone features resulted to be the main factors influencing
      temperature rise during piezoelectric implant site preparation. Irrigant
      temperature and clogging effect may also synergically contribute to the heat
      generation.

PMID- 25774246
TI  - Multitarget survey on the Finance Police personnel: assessment of the health
      condition.
AB  - INTRODUCTION: Over the past 10-15 years, Italy has undergone a social
      transformation, and the class of employees and workers has become more
      economically stable with a higher buying power. Along with the increased
      expectations of patients on the quality of life, it has now become a priority to
      make health and social services ready to face users bearing new requirements and
      different needs. OBJECTIVES: To provide a description of the state of health of
      the operating personnel of the Finance Police (Guardia di Finanza), including
      elements for planning the most appropriate interventions for health promotion and
      prevention. METHODS: The study analyzed the health condition of a group of
      soldiers (178 subjects, divided into different age classes) by evaluating the
      effectiveness of a training and information program and subsequently the level of
      benefit. RESULTS: The study population showed a good state of health correlated
      to the quality of life. Although the population voluntarily submitted to health
      assessment, the rigour of the calls and briefings carried out in the military
      health unit and the attention of the group to follow instructions on prevention
      underlined a positive trend, even in behaviours considered as health-risky.
      CONCLUSIONS: Socio-cultural components and the work environment influence the
      quality of life. In the case of military health care, the specific military
      organization was useful to monitor the health condition of the population,
      maximizing the effectiveness of services, enhancing the information and carrying
      out prevention strategies and demand of care, which should be an example for the
      public health services.

PMID- 25774247
TI  - Awareness of risks related to oral piercing in Italian piercers. Pilot study in
      Lazio Region.
AB  - OBJECTIVE: Specific regulations about education and training for body piercing
      licensure courses have to be considered due to the great increase in oral
      piercing practices. The aim of the present survey was to assess the local and
      systemic risk awareness in the practice of oral piercing and their prevention in
      a sample of Italian piercers. MATERIALS AND METHODS: An anonymous 20-item
      questionnaire was administered to 30 body licensed piercers in a small town of
      central Italy. Licenses certificates were issued by Lazio Region after the
      completion of an approved training program for standard body piercing including
      90 hours of course and a final examination as provided by regional law. The
      questionnaire surveyed on oral cavity anatomy, local and systemic risks as result
      of oral piercing, piercing maintenance and need of a dental visit. RESULTS:
      Response rate was 66.6%. Only 20% of respondents was aware about oral cavity
      anatomy and none had knowledge about tongue and gums anatomy. Only 10%
      enlightened the need of a dental visit and 30% was aware about piercingrelated
      temporary paralysis. The piercing maintenance was habitually proposed only by 40%
      of respondents. CONCLUSION: The study participants showed a low level of
      awareness regarding the potential health risks of oral piercing. Poor knowledge
      of anatomy and local and systemic risks and poor awareness of the importance of
      piercing maintenance explanation.

PMID- 25774248
TI  - Socio-demographic inequalities and teeth extraction in the last 12 months in
      Italy.
AB  - AIMS: Teeth loss represents a major concern for the global oral health status of
      a population. The aim of this study was to describe the prevalence of teeth
      extraction among the Italian adult population, analyzing the association between
      teeth extraction in the last 12 months and socio-demographic characteristics.
      METHODS: This cross-sectional study is based on the national survey 'Health
      Conditions and Healthcare Services Use', carried out by the Italian National
      Centre of Statistics (ISTAT) in 2005. A univariate analysis was performed to
      investigate the association between the dependent and the independent variables
      (teeth extraction Vs socio-demographic characteristics). Multiple logistic
      regression analysis was conducted to assess the influence on the outcome (teeth
      extraction Yes/No). RESULTS: The present study highlights the relationship
      between teeth extraction and socio-demographic factors. Out of 128,040
      individuals, the sampled population consisted of 124,677 subjects, representing
      56,400,323 individuals in the Italian population. The prevalence of teeth
      extraction in the last 12 months was 8.2%. Subjects who underwent teeth
      extraction in the last 12 months were prevalent female (8.6%), smokers (10.4%),
      with a primary education (9.2%), married (9.2%), in poor health conditions
      (9.3%), age category of 55-64 years (11.1%), from Northeast of Italy (8.5%), with
      scarce household income (8.4%). The multivariate analysis confirmed most of the
      results of the univariate analysis. CONCLUSIONS: Inequalities in health among
      groups of various socioeconomic status constitute one of the main challenges for
      public health; these inequalities might be reduced by improving educational
      opportunities, income distribution, health-related behaviour, or accessibility to
      health care.

PMID- 25774249
TI  - Clinical evaluation with 18 months follow-up of new PTTM enhanced dental implants
      in maxillo-facial post-oncological patients.
AB  - AIM: The aim of this study is to present 18 months follow-up results of porous
      tantalum trabecular metal-enhanced titanium dental implant (PTTM) in implant
      supported prosthesis in post-oncological patients. MATERIALS AND METHODS: A total
      of 25 PTTM implants were placed in each jaw of 6 patients that met specific
      inclusion and exclusion criteria. Resonance Frequency Analysis (RFA) was
      conducted and Implant stability was recorded in ISQ values (Osstell ISQ, Osstell
      AB, Goteborg, Sweden) at implant placement and after 2,4,6,12 and 18 months of
      functional loading. Mean bone loss was also evaluated at the same interval of
      time on each periapical radiographs, bone levels were calculated by measuring the
      distance from the implant shoulder to the first bone to implant contact. RESULTS:
      Cumulative implant survival rate is 100% (n=25/25) to date and mean ISQ values
      recorded were: 72.14+/-5.61 (range= 50-81) at surgery, 64.39+/-8.12 (range=44-74)
      after 2 months, 74.26+/-7.14 (range=44-74) after 4 months, 76.84+/-7.65 (range=60
      83) after 6 months, 78.13+/-4.14 (range=64-84) after 12 months and 80.22+/-6.23
      (range=68-89) after 18 months of functional loading. Mean crestal marginal bone
      loss was 0.19+/-0.25 mm after 2 months of functional loading on periapical
      radiographs, 0.22+/-0.4 mm at 4 months, 0.3+/-0.46 mm at 6 months, 0.57+/-0.62 at
      1 year and 0.64+/-0.60 mm after 18 months. CONCLUSIONS: The results of this
      study, even if limited by the number of implants placed indicate that PTTM dental
      implants have a clinical efficacy in prosthetic rehabilitation of post
      oncological patients, due to trabecular structure of the porous Ta metal that
      increases bone-implant connection values.

PMID- 25774250
TI  - Safe approach in "All-on-four" technique: a case report.
AB  - The "All-on-Four" concept is based on the placement of four implants in the
      anterior part of fully edentulous jaws to support a provisional, fixed, and
      immediately loaded full-arch prosthesis. Combining tilted and straight implants
      for supporting fixed prostheses can be considered a viable treatment modality
      resulting in a more simple and less time consuming procedure, in significantly
      less morbidity, in decreased financial costs and a more comfortable postsurgical
      period for the patients. The authors present a case report with mandibular
      atrophy and left mental foramina on the top of the residual crest. 

PMID- 25774251
TI  - The SYNTAX Score Can Predict Major Adverse Cardiac Events Following Percutaneous
      Coronary Intervention.
AB  - OBJECTIVES: The SYNTAX score is a grading system that evaluates the complexity
      and prognosis of patients undergoing percutaneous coronary intervention (PCI). We
      investigated the association between the incidence of major adverse cardiac
      events (MACE) following PCI and the SYNTAX score in patients with three-vessel
      disease. METHODS: We consecutively enrolled 381 patients with three-vessel
      disease undergoing PCI and stenting. The SYNTAX score was divided into tertiles
      as low (<=16), intermediate (16-22) and high (>22). The endpoint was the
      incidence of MACE defined as cardiac death, in-hospital mortality, nonfatal
      myocardial infarction (MI), or target vessel revascularization. Then, the
      incidence of MACE was compared among the SYNTAX score tertile groups. RESULTS:
      The median follow-up was 14 months, and the rate of MACE was 12.6%. The rates of
      MACE were 7.5%, 9.9%, and 21.6% in patients with low, intermediate, and high
      SYNTAX score tertiles, respectively. Higher SYNTAX scores significantly predicted
      a higher risk of MACE (hazard ratio = 2.36; P = 0.02) even after adjustment for
      potential confounders. The main predictors of MACE were SYNTAX score, advanced
      age, hyperlipidemia, presentation as recent ST-elevation MI, number of total
      lesions, and history of renal failure. CONCLUSION: The SYNTAX score could predict
      major cardiac outcomes following PCI in patients with three-vessel disease.

PMID- 25774252
TI  - The role of ischemia modified albumin in acute pulmonary embolism.
AB  - BACKGROUND: Acute pulmonary embolism (PE) is a life-threatening and a relatively
      common cardiovascular pathology. Although the pathogenesis of PE is well defined,
      there is no ideal diagnostic biochemical marker. Previous studies showed an
      increased ischemia modified albumin (IMA) levels in acute PE; however, the
      relationship between IMA and right ventricular (RV) dysfunction has not been
      examined. The aim of this study was to evaluate the diagnostic value of IMA and
      the relationship with RV dysfunction in acute PE. MATERIALS AND METHODS: A total
      of 145 patients (70 females) with suspected acute PE was enrolled to the study.
      Eighty-nine patients were diagnosed with acute PE via computed tomographic
      pulmonary angiography. Sixty-five patients with similar demographic and clinical
      characteristics were assigned to the control group. All patients were evaluated
      for RV dysfunction using transthoracic echocardiography. RESULTS: Serum IMA
      levels were significantly increased in acute PE compared with control group (0.41
      +/- 0.06 vs. 0.34 +/- 0.11, P = 0.001). There was no relationship between serum
      IMA levels and RV dysfunction. IMA levels were positively correlated with shock
      index and heart rate. Receiver operating curve analysis demonstrated that serum
      IMA levels higher than 0.4 put the diagnosis at sensitivity of 53.85% and at
      specificity of 85.96%. CONCLUSIONS: Although IMA levels are increased in patients
      with acute PE, it failed to predict RV dysfunction.

PMID- 25774254
TI  - Abnormal Chest X-ray Postmyocardial Infarction.
AB  - Pulmonary hemorrhage is a rare complication of fibrinolytic therapy. Only a few
      cases are reported in the literature. We present a patient who had myocardial
      infarction, treated with fibrinolytic therapy and developed pulmonary hemorrhage.
      We discuss the features that suggest and support the diagnosis. 

PMID- 25774255
TI  - Paradoxical coronary artery embolism - a rare cause of myocardial infarction.
AB  - Paradoxical coronary artery embolism is a rare, but often an underdiagnosed cause
      of acute myocardial infarction. It should be considered in patient who presents
      with chest pain and otherwise having a low risk profile for atherosclerosis
      coronary artery disease. We describe a case of paradoxical coronary artery
      embolism causing ST segment elevation myocardial infarction in a patient with
      upper extremity venous thrombosis. Echocardiography demonstrated a patent foramen
      ovale (PFO) with bidirectional shunt. In addition to treatment of acute coronary
      event closure of the PFO should be considered to prevent a recurrence. 

PMID- 25774253
TI  - Tight glycemic control and cardiovascular effects in type 2 diabetic patients.
AB  - Diabetes Mellitus (DM) with poor glycemic control is one of the leading causes
      for cardiovascular mortality in diabetic patients. Tight glycemic control with
      glycosylated haemoglobin of <7 gms% is recommended as a routine and < 6.5 gms% is
      recommended for young and newly diagnosed diabetics. Treatment goal aims at
      achieving near normal blood glucose level, and directed at management of other co
      morbid conditions such as obesity, hypertension and dyslipidemia. Oral
      hypoglycemic agents are the preferred drugs, alone or in combination. Preference
      for glitazones is declining due to the increasing evidences of associated adverse
      events. Gliptins appear as promising agents with lesser tendency to cause
      hypoglycemia, but their long term safety and efficacy is yet to be established.
      We emphasize the role of preventive measures in prediabetics and in established
      DM, treatment should be individualized and customized to minimize hypoglycemic
      effects and to retain quality of life. 

PMID- 25774256
TI  - Displacement of impella post chest compressions.
AB  - The Impella is a left ventricular assist device which is implanted via the
      transcutaneous femoral route and is placed across the aortic valve into the left
      ventricle. We report an interesting case where cardiopulmonary resuscitation was
      associated with displacement of Impella device. Impella is being increasingly
      used these days especially in patients with cardiogenic shock. Clinicians should
      have high index of suspicion for displacement of Impella in appropriate clinical
      setting. 

PMID- 25774257
TI  - Heart Failure Caused by Atrial Fibrillation in a Patient with Isolated
      Adrenocorticotropic Hormone Deficiency and Hashimoto's Thyroiditis.
AB  - We report the case of a 75-year-old female patient with a history of Hashimoto's
      thyroiditis who presented with congestive heart failure caused by atrial
      fibrillation associated with isolated adrenocorticotropic hormone (ACTH)
      deficiency. This is the first case of the combination of these complex
      conditions. Clinical conditions in a patient with isolated ACTH deficiency and
      Hashimoto's thyroiditis can be variable. Thus, it is sometimes difficult to
      establish a diagnosis. The mechanism underlying heart failure may be complex in
      some cases. Various conditions can affect patients simultaneously. Therefore,
      making a proper diagnosis is necessary to improve the patient's prognosis. 

PMID- 25774259
TI  - Art, medicine and technology.

PMID- 25774258
TI  - Acute stent thrombosis.

PMID- 25774260
TI  - Night blindness and ancient remedy.
AB  - The aim of this article is to briefly review the history of night blindness and
      its treatment from ancient times until the present. The old Egyptians, the
      Babylonians, the Greeks and the Arabs used animal liver for treatment and
      successfully cured the disease. The author had the opportunity to observe the
      application of the old remedy to a patient. Now we know what the ancients did not
      know, that night blindness is caused by Vitamin A deficiency and the animal liver
      is the store house for Vitamin A. 

PMID- 25774261
TI  - The selenium status in thalassemia patients in South East of iran.
AB  - INTRODUCTION: There are limited reports about selenium status in major
      thalassemia patients. The aim of this study is evaluation of selenium status in
      patients with major thalassemia south east of Iran with large sample size and
      wide range of age. This study compared selenium status with other sites of the
      world. METHODS: In this study 369 cases that had major thalassemia for more than
      5 years were enrolled in the study. Selenium level was measured in all eligible
      patients after 12 hours fasting by graphite enstrum furnace atomic absorption
      spectrometry in south east of Iran in 2012. RESULTS: Of 369 cases, 333 eligible
      patients were evaluated. Mean age was 15.63+/-7.4 years. One hundred ninety two
      cases were male and others were female (141 Cases). About 27% (90) of the cases
      were 5-10 years-old, 24 % (80) were 10-15 years-old and 49% were more than 15
      years-old. Iron chelator in 62.2% was Dessferrioxamine, in 15.5% was Deferiprone
      and in 22.3% was combination of Dessferioxamine and Deferiprone. Totally 85 cases
      (25.52%) had Selenium deficiency, 35.43% (118 cases) had normal levels and 39
      %(130 cases) had selenium excess. CONCLUSION: Our study on 333 major thalassemia
      cases documented variable status of selenium from deficiency to higher than
      normal levels. It was different with other reports in the world.

PMID- 25774262
TI  - Association of Deficiency of Coagulation Factors (Prs, Prc, ATIII) and FVL
      Positivity with Preeclampsia and/or Eclampsia in Pregnant Women.
AB  - BACKGROUND: Thrombophilia is a pathological state of increased blood
      coagulability. It causes problems during pregnancy including preeclampsia,
      stillbirth, repeated abortions, and detached pair. Out of the most prevalent
      factors causing inherited thrombophilia, protein S (Prs), protein C (Prc), and
      antithrombin III (ATIII) deficiency, and Factor V Leiden (FVL) mutation could be
      mentioned. This study aimed to investigate association of these parameters with
      preeclampsia. METHODS: In this case-control study, 142 pregnant women with
      preeclampsia referred to Obstetric Clinic of Hajar Hospital, southwest of Iran,
      were assigned to the case group after clinical laboratory tests and according to
      specialist point of view and 142 pregnant women with normal blood pressure were
      assigned to the control group. After obtaining consent and completing relevant
      questionnaire, a 4-cc blood sample was taken from the patients. Coagulation
      factors and FVL rate were measured and after 6 months patients were followed- up.
      Data analysis was done by SPSS software using t-test. RESULTS: In view of
      deficiency of Prs, Prc, and ATIII, no statistically significant association was
      observed between case and control groups (P>0.05). Statistical t-test indicated
      that the rate of FVL deficiency in pregnant patients with preeclampsia was
      significantly different from that in the control group (p=0.03). In addition, the
      body mass index of case group was significantly higher than that of control group
      prior to pregnancy (P=0.001). In case group, preeclampsia history contributed to
      development of current preeclampsia in contrast to control group (p<0.001). The
      patients of case group were followed up after 6 months in view of blood pressure
      and all had a normal mean blood pressure at the completion of the study.
      CONCLUSION: Measurement of FVL deficiency could help to decrease the unpleasant
      complications of vascular disorders during pregnancy. But, screening test for pre
      eclampsia does not seem necessary to determine the deficiency of coagulation
      factors, Prs, Prc, and ATIII.

PMID- 25774263
TI  - Differentiation of bone marrow mesenchymal stem cells into chondrocytes after
      short term culture in alkaline medium.
AB  - BACKGROUND: Bone marrow mesenchymal stem cells (MSCs) are one of the
      undifferentiated multipotential cell sources of human body. MSCs have the
      capacity to form a variety of cell types, especially chondrocytes and osteocytes.
      Learning about responses of MSCs to external milieu and chemical factors such as
      pH could recommend new approaches for preparation of suitable scaffolds for bone
      and cartilage tissue engineering. In present study, the effect of alkaline medium
      on chondrogenic and osteogenic differentiation of rat MSCs was evaluated.
      METHODS: MSCs were harvested from bone marrow of animals and then the response of
      passage1 and 2 of MSCs (P1 MSCs & P2 MSCs) to the culture in alkaline medium (pH:
      8) was evaluated. Cytochemical and immunocytochemical staining were performed to
      distinguish chondrocytes and osteocytes. Real-time PCR was performed to evaluate
      the type II collagen and osteopontin mRNA levels. RESULTS: Staining for type II
      collagen, a chondrocytic specific marker, revealed that after one-week culture in
      alkaline medium, a considerable amount of P1 MSCs had shown chondrocytic
      morphology. By prolonging the culture period up to 4 weeks, osteogenic cells with
      expanded matrix and mineralized areas around them were appeared. Results of real
      time PCR showed that P1 MSCs after one week culture in alkaline medium expressed
      highest rate of type II collagen and osteopontin mRNA among all groups.
      CONCLUSION: This study demonstrated that alkaline medium is a potent chondrogenic
      differentiation inducer for MSCs in their first passage.

PMID- 25774264
TI  - Efficient Differentiation of Human Induced Pluripotent Stem Cell (hiPSC) Derived
      Hepatocyte-Like Cells on hMSCs Feeder.
AB  - BACKGROUND: The use of stem cells is considered as an appropriate source in cell
      therapy and tissue engineering. Differentiation of human induced Pluripotent Stem
      Cells (hiPSCs) to Hepatocyte-like Cells (HLCs) on mouse embryonic fibroblasts
      (MEFs) feeders is confronted with several problems that hinder the clinical
      applications of these differentiated cells for the treatment of liver injuries.
      Safe appropriate cells for stem cell-based therapies could create new hopes for
      liver diseases. This work focused on the determination of a capacity/efficiency
      for the differentiation of the hiPSCs into Hepatocyte-like Cells on a novel human
      adult bone marrow mesenchymal stem cells (hMSCs) feeder. MATERIALS AND METHODS:
      Undifferentiated human iPSCs were cultured on mitotically inactivated human adult
      bone marrow mesenchymal stem cells. A three-step differentiation process has been
      performed in presence of activin A which added for 3 days to induce a definitive
      endoderm formation. In the second step, medium was exchanged for six days.
      Subsequently, cells were treated with oncostatin M plus dexamethasone for 9 days
      to generate hepatic cells. Endodermic and liver-specific genes were assessed via
      quantitative reverse transcription-polymerase chain reaction and RT-PCR,
      moreover, immunocytochemical staining for liver proteins including albumin and
      alpha-fetoprotein. In addition, functional tests for glycogen storage, oil red
      examination, urea production and alpha-fetoprotein synthesis, as well as, cells
      differentiated with a hepatocyte-like morphology was also performed. RESULTS: Our
      results show that inactivated human adult bone marrow mesenchymal stem cell
      feeders could support the efficient differentiation of hiPSCs into HLCs. This
      process induced differentiation of iPSCs into definitive endocrine cells that
      expressed sox17, foxa2 and expression of the specific genes profiles in hepatic
      like cells. In addition, immunocytochemical analysis confirmed albumin and alpha
      fetoprotein protein expression, as well as, the hiPSCs-derived Hepatocyte-like
      Cells on human feeder exhibited a typical morphology. CONCLUSIONS: we suggested a
      successful and efficient culture for differentiation and maturation of
      hepatocytes on an alternative human feeders; this is an important step to
      generate safe and functional hepatocytes that is vital for regenerative medicine
      and transplantation on the cell-based therapies.

PMID- 25774265
TI  - Outcome of allogeneic hematopoietic stem cell transplantation in patients with
      hematological malignancies.
AB  - INTRODUCTION: Allogeneic hematopoietic stem cell transplantation is a potentially
      curative treatment modality for hematological malignancies. We evaluated the
      outcome of patients suffering from hematological malignancies, including acute
      leukemias, chronic myeloid leukemia and myelodysplastic syndrome after allogeneic
      transplantation. METHODS: All patients having hematological malignancies with HLA
      identical sibling donors who underwent allogeneic transplantation were included.
      Pre-transplant workup consisted of complete blood counts, evaluation of liver,
      kidneys, lungs, infectious profile, chest X-ray, paranasal sinus roentgenograms
      and dental review. Donors were given G-CSF at a dose of 5-10 MUg/kg/twice daily
      for five days prior to harvest. The conditioning regimens included
      cyclophosphamide, busulfan and total body irradiation. RESULTS: A total of 41
      allogeneic transplants were performed for hematological malignancies from April
      2004 to December 2012. There were 31 males and 10 females. Median age +/- SD was
      28 +/- 11.7 years (range 8 - 54 years). A mean of 7.7*108+/-1.5 mononuclear
      cells/kg were infused (range:6.2-9.2*108/kg). The median time to white cell
      recovery was 19+/-4 days (range:15-23 days). Transplant related mortality was
      19.5%. The median overall survival was 53.6 months. Overall survival at a median
      follow up of 37 months was 67%. CONCLUSION: Allogeneic stem cell transplantation
      is an effective treatment option in patients with hematological malignancies. Our
      outcomes are comparable with results from neighboring countries as well as the
      western world.

PMID- 25774266
TI  - Evaluation of rs3102735 and rs2073617 Osteoprotegerin Gene Polymorphisms and the
      Risk of Childhood Acute lymphoblastic Leukemia in Zahedan Southeast Iran.
AB  - INTRODUCTION: Osteoprotegerin (OPG), a soluble decoy receptor secreted by
      osteoblasts, binds RANK-L, preventing stimulation of osteoclastogenesis. In the
      present study we aimed to investigate the impact of OPG variants and
      susceptibility to childhood acute lymphocytic leukemia (ALL) in a sample of
      Iranian population. METHODS: This case-control study was done on 98 ALL and 124
      healthy children. We genotyped the polymorphisms using tetra-primer ARMS-PCR (T
      ARMS-PCR). RESULTS: Our findings showed that neither rs3102735 nor rs2073617
      variants were associated with ALL in a sample of Iranian population. Concerning
      rs3102735 polymorphism, the age of ALL predispositions was significantly higher
      in TC+CC genotype than TT genotype (P=0.032). Furthermore, the CSF involvement
      was significantly higher in ALL subjects carrying TC+CC genotype (p=0.044).
      CONCLUSION: We found no association between OPG (rs3102735, rs2073617) gene
      polymorphisms and risk of childhood ALL. Further studies with larger sample sizes
      and various ethnicities are necessary to verify our findings.

PMID- 25774267
TI  - Composite lymphoma in a patient with ulcerative colitis: a case report.
AB  - A 45-year-old female patient with a diagnosis of ulcerative colitis complicated
      with composite lymphoma in the spleen and para-aortic lymph node presented with a
      one-month history of malaise, weakness and fatigue. Only mesalamine kept
      ulcerative colitis under control. In physical examination, splenomegaly was
      revealed and pancytopenia was obtained from laboratory data. Computed tomography
      scan revealed para-aortic mediastinal lymphadenopathy with splenomegaly.
      Splenectomy and excisional biopsy of abdominal lymph node were performed and
      disease was diagnosed as composite lymphoma, consisting of diffuse large B-cell
      lymphoma and nodular sclerosing Hodgkin lymphoma. 

PMID- 25774268
TI  - Appearance and Disappearance of Chronic Myeloid Leukemia (CML) in Patient with
      Chronic Lymphocytic Leukemia (CLL).
AB  - Chronic lymphocytic leukemia (CLL) and chronic myeloid leukemia (CML) are the
      most common leukemias of the elderly (>43 year). However, the sequential
      occurrence of CML followed by CLL in the same patient is extremely rare. In our
      report, a 52-year-old female was diagnosed with CLL (type of bone marrow (BM)
      infiltration was nodular and interstitial) and was treated with chlorambucil. 64
      months after the diagnosis of CLL, she developed CML. She was treated with
      imatinib (400mg/day). After a few months, signs of CML were disappeared and CLL
      became dominant. This is first reported case. 

PMID- 25774269
TI  - Assessment Techniques to Detect Aspergillus fumigatus in Different Samples of
      Immunosuppressed Male Western Albino Rats.
AB  - BACKGROUND: There are several conventional, immunological and molecular
      techniques to diagnose the fungi that cause aspergillosis in biological samples;
      these methods have some advantages and disadvantages. OBJECTIVES: The current
      study aimed to evaluate different methods used in identification and diagnosis of
      fungi causing aspergillosis. MATERIALS AND METHODS: Male Western Albino rats were
      provided by Animal Care Unit at Faculty of Pharmacy, King Saud University. After
      adaptation for a reasonable period, rat's immunity was debilitated by injection
      of cyclophosphamide (i.p.); the infection was induced by injecting (i.v.) the
      prepared suspension of Aspergillus fumigatus spores. Blood samples, lung tissue,
      lung fluid smears and nasal fluid smears were obtained during the periods before
      and after injection. Isolation of fungus was carried out by synthetic media; and
      macro- and micro-characteristics were studied to identify the fungus. Enzyme
      linked immunesorbent (ELISA) and LightCycler-based PCR was employed to check the
      existence of the fungus in blood samples. RESULTS: The results indicated that all
      methods were unable to diagnose the A. fumigatus on the following day of
      infection except ELISA method; however, culturing methods varied according to the
      type of vital samples where lung tissue and lung fluid smears were the best.
      Moreover, more than half of the samples used in the culturing techniques had
      negative results. The highest rate of the cases diagnosed by ELISA and polymerase
      chain reaction (PCR) was recorded during the second week following the infection,
      and then it declined gradually till the end of the experiment. The molecular
      methods showed high efficiency followed by ELISA. CONCLUSIONS: It could be
      concluded that the best methods to identify A. fumigatus were molecular methods;
      however, the early diagnosis requires the enzymatic-immunological methods
      (ELISA). The current study recommends the integration among all possible
      techniques whenever the facilities are available. But when only microbiological
      methods are used, samples should be collected from different organs of the
      infected hosts.

PMID- 25774270
TI  - Antibiotics use patterns for surgical prophylaxis site infection in different
      surgical wards of a teaching hospital in ahvaz, iran.
AB  - BACKGROUND: Despite the effectiveness of prophylactic antimicrobials to prevent
      surgical site infection the use of antibiotic prophylaxis is often inappropriate.
      OBJECTIVES: The current study aimed to determine the pattern of prophylactic
      antibiotic use in a teaching hospital affiliated to Jundishapur University of
      Medical Sciences, Ahvaz, Iran. PATIENTS AND METHODS: The current descriptive
      study included 8586 patients who received prophylactic antibiotics before surgery
      from April 2011 to March 2012, in Razi Hospital affiliated to Jundishapur
      University of Medical Sciences. Indications for antibiotic use, proper or
      inappropriate antibiotics, an antibiotic or combination of antibiotics, dosage
      and length of treatment for each patient based on the infectious disease textbook
      (Mandel's Principle and practice of infectious diseases) definitions were
      administrated. RESULTS: Of the total 8586 patients who took antibiotics for
      preventive purposes, 4815 (56%) required antimicrobial prophylaxis, and 3771
      (44%) patients did not. Of the 4815 patients who received prophylaxis, 86.9%
      received it appropriately, 13.1% received it inappropriately; 8.2% received
      inappropriate dosage, and 9.5% received antibiotic longer than 24 hours.
      CONCLUSIONS: The current study revealed that 44% of those who received
      prophylaxis did not need it. In the patients who received antibiotics, the most
      common mistakes were antibiotic selection followed by prolonged prophylaxis (> 24
      hours) and excess dose.

PMID- 25774271
TI  - Detection of Metallo-Beta Lactamases Among Carbapenem-Resistant Pseudomonas
      aeruginosa.
AB  - BACKGROUND: Carbapenems are important drugs used for the treatment of Pseudomonas
      aeruginosa infections, however metallo-beta-lactamases (MBL) are able to
      efficiently hydrolyze these classes of drugs. Immediate detection of the MBL
      producing P. aeruginosa is necessary in order to accurately treat infections
      caused by this organism. OBJECTIVES: To determine the prevalence of MBL producing
      P. aeruginosa in burn and non-burn patients by two phenotypic tests and
      polymerase chain reaction (PCR) and to compare phenotypic tests with PCR.
      MATERIALS AND METHODS: A total of 223 non-duplicate strains of P. aeruginosa were
      collected from three teaching hospitals of Ahvaz, Iran. Antimicrobial
      susceptibility and minimum inhibitory concentrations (MICs) of carbapenems
      (imipenem, meropenem, doripenem and ertapenem) were determined by the Kirby-Bauer
      and E-test methods. Combined disk (CD) test, MBL E-test and PCR were performed
      for carbapenem-resistant P. aeruginosa isolates. RESULTS: Amongst all the P.
      aeruginosa isolates, 58.7% were resistant to imipenem while 31.8%, 13.5% and
      74.4% were resistant to meropenem, doripenem and ertapenem, respectively. Amongst
      all the P. aeruginosa isolates, 44.4% were multidrug resistant and 13.45% were
      resistant to all of the carbapenems. The CD test with doripenem disk / 750 MUg
      ethylene diamine tetra acetic acid (EDTA) had the highest efficiency compared to
      the other phenotypic tests. bla IMP and bla VIM genes were detected in 11.7% and
      0.4% of isolates, respectively. bla SPM and bla NDM genes were not observed.
      CONCLUSIONS: Epidemiological and regional evaluation of MBL-producing P.
      aeruginosa through simple and inexpensive methods should be considered for
      effective treatment of carbapenem-resistant P. aeruginosa infections.

PMID- 25774272
TI  - Shiga toxin-producing Escherichia coli isolated from lettuce samples in tehran,
      iran.
AB  - BACKGROUND: During the last decade, the prevalence of foodborne diseases due to
      contaminated food as well as the outbreaks of diseases due to Shiga toxin
      producing Escherichia coli (STEC) strains has increased. OBJECTIVES: The aim of
      this study was to evaluate the prevalence and antibiotic resistance pattern of
      STEC strains in lettuce samples. Since lettuce is used as a raw vegetable in
      salads, the rates of infections caused by this vegetable are high. MATERIALS AND
      METHODS: A total of 100 samples collected from Tehran, Iran, were transported to
      the laboratory, homogenized by a stomacher in E. coli broth containing cefixime,
      and cultured on MacConkey agar medium. Their DNA was extracted by boiling method
      and polymerase chain reaction (PCR) was performed, using five primers targeting
      the stx1, stx2, fliCh7, rbfO157, and eaeA genes. Susceptibility testing against
      ampicillin, imipenem, cephalosporin, tetracycline, aminoglycosides,
      chloramphenicol and quinolones was performed using disk diffusion method.
      RESULTS: Eight samples were positive for presence of STEC strains, three
      contained stx1, five contained stx2, and one sample was positive for presence of
      both rbfO157 and fliCh7. They were susceptible to all the antibiotics except for
      ampicillin and tetracycline. CONCLUSIONS: This study indicated the contamination
      of lettuce by STEC strains and its possible role as the source of infection.
      Resistance to both tetracycline and ampicillin may be considered as an emergency
      alarm for a multidrug resistance of STEC strains.

PMID- 25774273
TI  - Cloning of fliC Gene From Salmonella typhimurium in the Expression Vector pVAX1
      and Evaluation of its Expression in Eukaryotic Cells.
AB  - BACKGROUND: Flagellin is the main structural protein of the flagella of many
      pathogens including Salmonella typhimurium. It is a potent trigger of innate
      immune responses that enhance adaptive immune responses to a variety of protein
      antigens. Flagellin has intrinsic adjuvant activity mediated through toll-like
      receptor (TLR) 5 and is an attractive candidate for highly effective vaccine
      adjuvant conferring enhanced antibody and cellular immune responses to proteins
      or peptides. In the present study, we cloned the fliC gene from S. enterica
      typhimurium in eukaryote vector pVAX1 and evaluated its expression in eukaryotic
      cells. OBJECTIVES: The main aim of the present study was to construct a DNA
      vaccine expressing fliC as an adjuvant. MATERIALS AND METHODS: The fliC gene of
      S. typhimurium (ATCC 14028) was amplified by PCR with specific primers and cloned
      into the pPrime cloning vector and successfully subcloned into expression vector
      pVAX1. The recombinant plasmid pVAX-fliC was finally expressed in eukaryotic
      cells. RESULTS: Cloning and subcloning of the fliC gene were confirmed by colony
      PCR, restriction enzymes digestion and DNA sequencing of the recombinant plasmids
      pPrime-fliC and pVAX-fliC. The expression of flagellin protein in eukaryotic
      cells was approved by immunofluorescence assay (IFA), western blotting analysis
      and the reverse transcriptase polymerase chain reaction (RT-PCR) method.
      CONCLUSIONS: The results of this study demonstrated that the fliC gene in
      recombinant plasmid pVAX-fliC was successfully expressed in eukaryotic cells and
      produced flagellin protein, which could be used as an effective adjuvant for DNA
      vaccine research.

PMID- 25774274
TI  - Status of pertussis in iran.
AB  - BACKGROUND: Pertussis is a respiratory and contagious disease which is mostly
      caused by Bordetella pertussis and B. parapertussis. It usually spreads from
      person to personduring the incubation or catarrhal phase of the disease. Despite
      of large-scale vaccination, whooping cough is still an endemic disease with
      several outbreaks. OBJECTIVES: The aim of this study was to determine the
      prevalence of pertussis and identify its causative agents, B. pertussis or B.
      parapertussis, from specimens collected from Iranian patients from 2004 to 2008.
      PATIENTS AND METHODS: Nasopharyngeal swab samples from 347 suspected pertussis
      cases were collected from 18 provinces of Iran. The patients were in different
      age groups and were either unvaccinated or vaccinated for pertussis with whole
      cell vaccine (WCV). Bacterial culture, agglutination tests and quantitative PCR
      (qPCR) targeting IS481 and IS1001 for B. pertussis and B. parapertussis were done
      for every specimen, respectively. RESULTS: The results showed that seven
      nasopharyngeal swab samples (2%) were positive for B. pertussis (1.7%) and B.
      parapertussis (0.3%) by culture and agglutination test and 30 patients had
      positive qPCR test results (9%). CONCLUSIONS: Despite the fact that bacterial
      culture is the golden standard for the detection of B. pertussis, direct
      detection of bacteria from nasopharyngeal specimens can be performed by a rapid
      qPCR assay. In this study, high percentage of positive qPCR cases may indicate
      that the patients might have recovered from pertussis following antibiotic
      treatment before samples were collected. Rapid detection by qPCR could be
      important for immediate diagnosis and treatment of patients with pertussis.

PMID- 25774275
TI  - Toxoplasma gondii Exposure and the Risk of Schizophrenia.
AB  - BACKGROUND: Schizophrenia is a major psychiatric disorder with a deeply
      destructive pathophysiology. There are evidences to indicate that infectious
      agents such as Toxoplasma gondii may play some roles in etiology of the disorder.
      OBJECTIVES: The current study aimed to determine the association between T.
      gondii exposure and the risk of schizophrenia. MATERIALS AND METHODS: T. gondii
      IgG antibodies of 100 patients with schizophrenia as well as 200 healthy
      volunteers were assessed. The subjects also completed demographic questionnaires.
      Data was analyzed using the chi-square and Fisher exact tests. RESULTS: The
      analyses confirmed the significant differences between healthy women and ones
      with schizophrenia (P = 0.001) as well as between males and females with
      schizophrenia (P = 0.009) in IgG positivity. CONCLUSIONS: The present study
      supported the contamination with T. gondii as a risk factor for schizophrenia
      just in women.

PMID- 25774276
TI  - GB virus C Viremia and Anti-E2 Antibody Response Among Hemodialysis Patients in
      Gorgan, Iran.
AB  - BACKGROUND: GB Virus C is a blood-borne virus and a member of Flaviviridae, like
      hepatitis C that is distributed globally and puts hemodialysis patients at high
      risk of developing liver disease. The clinical significance of GBV-C in this
      population remains unclear. OBJECTIVES: The current study aimed to evaluate GBV-C
      infection among hemodialysis patients. PATIENTS AND METHODS: Totally, 149
      patients receiving hemodialysis were included in the study. The detection of GBV
      C sequences in plasma was done by the nested Reverse transcription polymerase
      chain reaction (RT-PCR) using specific primers selected from highly conserved
      regions of 5' UTR of GBV-C and antibodies to the envelope protein of GBV-C (anti
      E2 GBV-C antibody) were analyzed by also serological methods. In addition,
      Hepatitis B surface antigen (HBsAg), Hepatitis B core antibody (HBcAb) IgM, anti-
      Hepatitis C virus (HCV) and anti- hepatitis E virus (HEV) Ab was determined in
      patients who were GBV-C RNA and anti-E2 GBV-C antibody positive. RESULTS: The
      total prevalence of GBV-C infection was 14.7% (95%CI: 0.09-0.21) among patients
      receiving hemodialysis. The rate of GBV-C viremia and anti-E2 antibody positivity
      were 6.04% and 10.73%, respectively. Among the subjects who were positive for GBV
      C, 27.27% (95% CI: 0.02-0.09), 45.45% (95% CI: 0.03-0.11), 59.9% (95% CI: 0.06
      0.16) and 0% (95% CI: 0.01-0.07) were positive for anti-HCV, anti-HBsAg, anti-HBc
      IgM and anti-(HEV) Ab, respectively. In addition, the rate of both anti-HBc IgM
      /anti-HCV/ HBsAg and anti-HBc IgM /anti-HCV positivity in GBV-C infected cases
      were 9.09%. The liver enzymes were normal in all of them. There was significant
      difference between GBV-C exposures with viral hepatitis co-infection, but there
      was no correlation between GBV-C exposure with gender, age, ethnicity, time on
      dialysis and history of blood transfusions. A relatively high frequency of
      positivity GBV-C-exposure among hemodialysis patients suggested that the
      transmission route for GBV-C may be nosocomial transmission, and via
      transfusions. CONCLUSIONS: The current study found a relatively high frequency of
      positivity GBV-C-exposure among the patients receiving hemodialysis in the area
      understudy. Nosocomial transmission seems to be the main route of GBV-C infection
      in the area.

PMID- 25774277
TI  - Antibacterial Effect of Garlic Aqueous Extract on Staphylococcus aureus in
      Hamburger.
AB  - BACKGROUND: Using garlic is widespread in Iran and other countries as a medicine
      and a natural spice. Garlic is a potential inhibitor for food pathogens. Foods
      contaminated with pathogens pose a potential danger to the consumer's health. The
      use of garlic can increase the shelf life and decrease the possibilities of food
      poisoning and spoilage in processed foods. OBJECTIVES: The aim of this study was
      to investigate the antibacterial effect of garlic aqueous extract on growth of
      Staphylococcus aureus bacteria. MATERIALS AND METHODS: In this study, the garlic
      aqueous extract was prepared under sterile conditions and was added in 1, 2, and
      3 mL to 100g hamburger samples. A group of samples was prepared to be used as
      treatment sample, while a group was stored at 4 degrees C and -18 degrees C. The
      samples were kept in refrigerator for one and two weeks and they were frozen for
      one, two and three months and then subjected to microbial tests. RESULTS:
      Statistical evaluation of the first and second week samples indicated a
      significant growth decreased by all the 1, 2, and 3-mL extracts. In treatment of
      one, two and three-month samples, the growth of S. aureus was significantly
      decreased by the 2 and 3-mL extracts. The 1-mL extract was effective in
      decreasing the growth, and a significant difference was observed in treatments
      with 2 and 3-mL extracts. However, there was no significant difference between
      the two and three-month samples, though they were significantly different from
      the one-month samples. After evaluations, treatment with the 2-mL extract was
      found to be the best one. CONCLUSIONS: Garlic aqueous extract has antibacterial
      properties against S. aureus present in hamburger. Moreover, garlic aqueous
      extract can be used not only as a flavor but also as a natural additive for
      hamburger. In addition, garlic has antibacterial properties against other Gram
      positive and Gram-negative bacteria, which must be investigated in further
      studies.

PMID- 25774278
TI  - Babesia infection in the southwest of china, a case report.
AB  - INTRODUCTION: Babesiosis is caused by apicomplexa parasites of the genus Babesia.
      Humans are commonly infected by Babesia through tick bites. There is limited
      information available about Babesia infection of humans in China. The aim of this
      study was to isolate the pathogen from a patient with severe parasitemia. CASE
      PRESENTATION: Blood samples were observed by transmission electron microscopy
      (TEM) and indirect fluorescent antibody (IFA), and red blood cells of bone marrow
      and blood smears were examined by a microscope. The patient was infected by
      Babesia and cured after a combined treatment. CONCLUSIONS: Babesia infection was
      detected in an individual from China.

PMID- 25774279
TI  - Prevalence of Extended Spectrum beta-lactamase-Producing Klebsiella pneumoniae in
      Clinical Isolates.
AB  - BACKGROUND: Extended spectrum beta-lactamase (ESBL) are gram-negative bacteria
      that produce the enzyme, beta-lactamase, which can break down commonly used
      antibiotics, such as penicillin and cephalosporins, making infections with ESBL
      producing bacteria more difficult to treat. Extended spectrum beta-lactamase
      producing Klebsiella pneumoniae were first reported in 1983 from Germany, and
      since then a steady increase in resistance against cephalosporins has been seen
      causing health problems. OBJECTIVES: The aim of this study was to determine the
      prevalence of ESBL in strains of K. pneumoniae isolated from different clinical
      samples. PATIENTS AND METHODS: One hundred and thirty isolates of K. pneumoniae
      were isolated from different clinical specimens from King Khalid hospital, Hafr
      Elbatin, Kingdom Saudi Arabia. These isolates were then characterized, tested for
      antimicrobial susceptibility and screened for ESBL production by the MicroScan
      WalkAway-96 SI System. Extended spectrum beta-lactamase production was confirmed
      by the phenotypic confirmatory disc diffusion test (PCDDT) and the double disc
      synergy test (DDST). RESULTS: Overall, 76.9% (100) of the isolates were resistant
      to cefuroxime, cefepime and cefazolin, 69.23% (90) were resistant to cefotaxime,
      and 46.15% (60) were resistant to cefoxitin. Extended spectrum beta-lactamase was
      detected in 53.8% (70) of K. pneumoniae as detected by the MicroScan "WalkAway
      96" SI System and 50.07% (66) by PCDDT and 46.15% (60) by DDST. All K. pneumoniae
      isolates were resistant to ampicillin followed by both piperacillin and
      mezlocillin 92.30% (120). K. pneumoniae isolates showed high sensitivity to
      imipenem (15.38%) (20), followed by ertapenem, tetracycline, tigecycline
      pipracilline/tazobactam and amikacin (23.07%) (30). CONCLUSIONS: Our study showed
      that the prevalence of ESBL-producing K. pneumoniae at King Khalid Hospital was
      significantly high. Routine detection of ESBL-producing microorganisms is
      required by each of the laboratory standard detection methods to control the
      spread of these infections and allow a proper therapeutic strategy. For
      detection, the phenotypic confirmatory disc diffusion test is simple, sensitive
      and cost effective. However, there is a need for larger scale drug susceptibility
      surveillance.

PMID- 25774280
TI  - Neuroendocrine and behavioral response to social rupture and repair in
      preschoolers with autism spectrum disorders interacting with mother and father.
AB  - BACKGROUND: Preschoolers with autism spectrum disorder (ASD) exhibit difficulties
      in handling social stress and utilizing efficient emotion regulation (ER)
      strategies to manage high arousal. While researchers called to assess ER in ASD,
      few studies utilized direct observations. We tested children's behavioral and
      cortisol response to maternal and paternal unavailability and hypothesized that
      children with ASD will employ less complex ER strategies and their parents would
      show increased regulation facilitation effort to accommodate their child's
      difficulties. METHODS: Forty preschoolers with ASD were matched with 40 typically
      developing (TD) preschoolers. Children were seen twice for identical battery with
      mother or father in the face-to-face-still-face paradigm, a three-episode
      paradigm where parent-child play (free play (FP)) is interrupted by elimination
      of communication (still face (SF)) followed by resuming play (reunion (RE)).
      Micro-coding of parent and child's social behavior and ER strategies was
      conducted. Parent and child's cortisol was assessed at baseline, following
      stress, and at recovery. RESULTS: Children with ASD exhibited the typical SF
      effect, indexed by an increase in negative affect and decrease in positive
      communications, but employed more simple regulatory behavior (self-soothing,
      proximity-seeking) and less complex strategies involving attention redirection
      and substitutive play. Their parents used more regulation-facilitation behavior,
      both simple and complex. All children showed initial cortisol response to
      novelty, which declined over time. However, maternal presence suppressed initial
      cortisol response in children with ASD. CONCLUSIONS: Children with ASD form
      typical expectations of parental availability and their parents increase effort
      to help repair social rupture. Among children with ASD, maternal presence and
      regulation facilitation provide social buffering for the child's HPA stress
      response in a manner similar to mammalian neonates. Results highlight the
      importance of assessing ER by combining direct observations and physiological
      measures and including fathers in empirical studies and intervention efforts for
      children with ASD during sensitive periods for social growth.

PMID- 25774281
TI  - Autistic children at risk of being underestimated: school-based pilot study of a
      strength-informed assessment.
AB  - BACKGROUND: An important minority of school-aged autistic children, often
      characterized as 'nonverbal' or 'minimally verbal,' displays little or no spoken
      language. These children are at risk of being judged 'low-functioning' or
      'untestable' via conventional cognitive testing practices. One neglected avenue
      for assessing autistic children so situated is to engage current knowledge of
      autistic cognitive strengths. Our aim was thus to pilot a strength-informed
      assessment of autistic children whose poor performance on conventional
      instruments suggests their cognitive potential is very limited. METHODS: Thirty
      autistic children (6 to 12 years) with little or no spoken language, attending
      specialized schools for autistic children with the highest levels of impairment,
      were assessed using Wechsler Intelligence Scale for Children (WISC-IV), Raven's
      Colored Progressive Matrices board form (RCPM), Children's Embedded Figures Test
      (CEFT), and a visual search task. An age-matched control group of 27 typical
      children was also assessed. RESULTS: None of the autistic children could complete
      WISC-IV; only six completed any subtest. In contrast, 26 autistic children could
      complete RCPM, with 17 scoring between the 5th and 90th percentile. Twenty-seven
      autistic children completed the visual search task, while 26 completed CEFT, on
      which autistic children were faster than RCPM-matched typical children. Autistic
      performance on RCPM, CEFT, and visual search were correlated. CONCLUSION: These
      results indicate that 'minimally verbal' or 'nonverbal' school-aged autistic
      children may be at risk of being underestimated: they may be wrongly regarded as
      having little cognitive potential. Our findings support the usefulness of
      strength-informed approaches to autism and have important implications for the
      assessment and education of autistic children.

PMID- 25774282
TI  - Effects of autism spectrum disorders on outcome in teenage-onset anorexia nervosa
      evaluated by the Morgan-Russell outcome assessment schedule: a controlled
      community-based study.
AB  - BACKGROUND: The purpose of the study was to evaluate time trends and effects of
      co-existing autism spectrum disorders (ASD) on outcome in an ongoing long-term
      follow-up study of anorexia nervosa (AN). METHODS: The Morgan-Russell Outcome
      Assessment Schedule (MROAS) was used at 6-, 10- and 18-year follow-up of a
      representative sample of 51 individuals with teenage-onset AN and a matched group
      of 51 healthy comparison cases. The full multinomial distribution of responses
      for the full scale and each of the subscales was evaluated using exact
      nonparametric statistical methods. The impact of diagnostic stability of ASD on
      outcome in AN was evaluated in a dose-response model. RESULTS: There were no
      deaths in either group. Food intake and menstrual pattern were initially poor in
      the AN group but normalised over time. MROAS 'mental state' was much poorer in
      the AN group and did not improve over time. The psychosexual MROAS domains
      'attitudes' and 'aims' showed persistent problems in the AN group. In the MROAS
      socioeconomic domain, the subscales 'personal contacts', 'social activities' and
      'employment record' all showed highly significant between-group differences at
      all three follow-ups. A statistically significant negative dose-response
      relationship was found between a stable diagnosis of ASD over time and the
      results on the subscales 'mental state', 'psychosexual state' and 'socio-economic
      state'. CONCLUSIONS: Outcome of teenage-onset AN is favourable with respect to
      mortality and persisting eating disorder, but serious problems remain in the
      domains 'mental state', 'psychosexual function' and 'socioeconomic state'.
      Outcome is considerably worse if ASD is present. Treatment programmes for AN need
      to be modified so as to accommodate co-existing ASD.

PMID- 25774284
TI  - Section level search functionality in Europe PMC.
AB  - BACKGROUND: As the availability of open access full text research articles
      increases, so does the need for sophisticated search services that make the most
      of this new content. Here, we present a new feature available in Europe PMC that
      allows selected sections of full text articles to be searched, including figures
      and reference lists. Users can now search particular parts of an article,
      reducing noise and allowing fine-tuning of searches. RESULTS: To the best of our
      knowledge, Europe PMC is the first service that provides a granular literature
      search by allowing users to target their search to particular sections of
      articles. This new functionality is based on a heuristic algorithm that
      identifies and categorises article sections into 17 pre-defined categories based
      on the section heading. The tagger's performance is measured against a manually
      curated dataset consisting of 100 full text articles with an F-score of 98.02%.
      CONCLUSIONS: The section search is available from the advanced search within
      Europe PMC (http://europepmc.org). The source code is freely available from
      http://europepmc.org/ftp/oa/SectionTagger/.

PMID- 25774283
TI  - Atypical development of white matter microstructure of the corpus callosum in
      males with autism: a longitudinal investigation.
AB  - BACKGROUND: The corpus callosum is the largest white matter structure in the
      brain, and it is the most consistently reported to be atypical in diffusion
      tensor imaging studies of autism spectrum disorder. In individuals with typical
      development, the corpus callosum is known to undergo a protracted development
      from childhood through young adulthood. However, no study has longitudinally
      examined the developmental trajectory of corpus callosum in autism past early
      childhood. METHODS: The present study used a cohort sequential design over 9
      years to examine age-related changes of the corpus callosum in 100 males with
      autism and 56 age-matched males with typical development from early childhood
      (when autism can first be reliably diagnosed) to mid-adulthood (after development
      of the corpus callosum has been completed) (3 to 41 years of age). RESULTS: The
      group with autism demonstrated a different developmental trajectory of white
      matter microstructure in the anterior corpus callosum's (genu and body)
      fractional anisotropy, which suggests atypical brain maturation in these regions
      in autism. When analyses were broken down by age group, atypical developmental
      trajectories were present only in the youngest participants (10 years of age and
      younger). Significant main effects for group were found in terms of decreased
      fractional anisotropy across all three subregions of the corpus callosum (genu,
      body, and splenium) and increased mean diffusivity, radial diffusivity, and axial
      diffusivity in the posterior corpus callosum. CONCLUSIONS: These longitudinal
      results suggest atypical early childhood development of the corpus callosum
      microstructure in autism that transitions into sustained group differences in
      adolescence and adulthood. This pattern of results provides longitudinal evidence
      consistent with a growing number of published studies and hypotheses regarding
      abnormal brain connectivity across the life span in autism.

PMID- 25774286
TI  - The evolution of sex differences in disease.
AB  - It is now becoming widely recognized that there are important sex differences in
      disease. These include rates of disease incidence, symptoms and age of onset.
      These differences between the sexes can be seen as a subset of the more general
      phenomenon of sexual dimorphism of quantitative phenotypes. From a genetic point
      of view, this is paradoxical, since the vast majority of genetic material is
      shared between the sexes. How can males and females differ in so many ways and
      yet have a common genetic code? Traditionally, the modifying action of hormones
      has been offered as a solution to this paradox, but experiments disentangling the
      effects of hormones and sex-chromosomes have shown that this cannot be the sole
      explanation. In this review, I outline current ideas about the evolutionary
      origins of sex differences in phenotypes, with a particular focus on how sex
      differences in disease can arise. I also discuss how sex differences in
      themselves can generate new risk factors for disease, in effect becoming a new
      environmental factor, as well as briefly reviewing more general evidence for
      sexually antagonistic selection and genetic variation within humans. Taking an
      evolutionary view on sex differences in disease provides an opportunity for
      greater understanding of mechanisms of disease and as such provides a clear
      motivation for clinicians to explore how therapies may be tailored to the
      individual in a sex-dependent way. 

PMID- 25774285
TI  - Pressor responsiveness to angiotensin II in female mice is enhanced with age:
      role of the angiotensin type 2 receptor.
AB  - BACKGROUND: The pressor response to angiotensin II (AngII) is attenuated in adult
      females as compared to males via an angiotensin type 2 receptor (AT2R)-dependent
      pathway. We hypothesized that adult female mice are protected against AngII
      induced hypertension via an enhanced AT2R-mediated pathway and that in
      reproductively senescent females this pathway is no longer operative. METHODS:
      Mean arterial pressure was measured via telemetry in 4-month-old (adult) and 16
      month-old (aged) and aged ovariectomized (aged-OVX) wild-type and AT2R knockout
      (AT2R-KO) female mice during baseline and 14-day infusion of vehicle (saline) or
      AngII (600 ng/kg/min s.c.). Real-time reverse transcription polymerase chain
      reaction (RT-PCR) was used to determine renal gene expression of angiotensin
      receptors and angiotensin-converting enzyme 2 in response to 14-day treatment
      with vehicle or AngII. RESULTS: Basal mean arterial pressure was similar between
      the groups. The pressor response to AngII was augmented in adult AT2R-KO compared
      to adult wild-type mice (29 +/- 3 mmHg versus 10 +/- 4 mmHg, respectively, on day
      14 as compared to basal mean arterial pressure, P = 0.002). In wild-type mice,
      pressor responsiveness to AngII was augmented with age, such that the pressor
      response to AngII was similar between aged AT2R-KO and wild-type female mice (31
      +/- 4 mmHg versus 34 +/- 3 mmHg, respectively, on day 14, P = 0.9). There were no
      significant differences in pressor responsiveness to AngII between aged and aged
      OVX mice. Vehicle-treated aged wild-type mice had a lower renal AT2R/AT1R balance
      as compared to adult counterparts. In response to AngII, the renal AT2R/AT1R
      balance in aged wild-type females was greater than that observed in vehicle
      treated aged wild-type females and adult wild-type females, yet the protective
      effects of AT2R activation were not restored. CONCLUSIONS: The protective role of
      the AT2R depressor pathway is lost with age in female mice. Therefore, targeting
      deficits in AT2R expression and/or signaling may represent a novel anti
      hypertensive approach in aged females.

PMID- 25774287
TI  - Int6 reduction activates stromal fibroblasts to enhance transforming activity in
      breast epithelial cells.
AB  - BACKGROUND: The INT6 gene was first discovered as a site of integration in mouse
      mammary tumors by the mouse mammary tumor virus; however, INT6's role in the
      development of human breast cancer remains largely unknown. By gene silencing, we
      have previously shown that repressing INT6 promotes transforming activity in
      untransformed human mammary epithelial cells. In the present study, guided by
      microarray data of human tumors, we have discovered a role of Int6 in stromal
      fibroblasts. RESULTS: We searched microarray databases of human tumors to assess
      Int6's role in breast cancer. While INT6 expression levels, as expected, were
      lower in breast tumors than in adjacent normal breast tissue samples, INT6
      expression levels were also substantially lower in tumor stroma. By
      immunohistochemistry, we determined that the low levels of INT6 mRNA observed in
      the microarray databases most likely occurs in stromal fibroblasts, because far
      fewer fibroblasts in the tumor tissue showed detectable levels of the Int6
      protein. To directly investigate the effects of Int6 repression on fibroblasts,
      we silenced INT6 expression in immortalized human mammary fibroblasts (HMFs).
      When these INT6-repressed HMFs were co-cultured with breast cancer cells, the
      abilities of the latter to form colonies in soft agar and to invade were
      enhanced. We analyzed INT6-repressed HMFs and found an increase in the levels of
      a key carcinoma-associated fibroblast (CAF) marker, smooth muscle actin.
      Furthermore, like CAFs, these INT6-repressed HMFs secreted more stromal cell
      derived factor 1 (SDF-1), and the addition of an SDF-1 antagonist attenuated the
      INT6-repressed HMFs' ability to enhance soft agar colony formation when co
      cultured with cancer cells. These INT6-repressed HMFs also expressed high levels
      of mesenchymal markers such as vimentin and N-cadherin. Intriguingly, when
      mesenchymal stem cells (MSCs) were induced to form CAFs, Int6 levels were
      reduced. CONCLUSION: These data suggest that besides enhancing transforming
      activity in epithelial cells, INT6 repression can also induce fibroblasts, and
      possibly MSCs as well, via mesenchymal-mesenchymal transitions to promote the
      formation of CAFs, leading to a proinvasive microenvironment for tumorigenesis.

PMID- 25774288
TI  - Food allergy in the Netherlands: differences in clinical severity, causative
      foods, sensitization and DBPCFC between community and outpatients.
AB  - BACKGROUND: It is unknown whether food allergy (FA) in an unselected population
      is comparable to those from an outpatient clinic population. OBJECTIVE: To
      discover if FA in a random sample from the Dutch community is comparable to that
      of outpatients. METHODS: This study was part of the Europrevall-project. A random
      sample of 6600 adults received a questionnaire. Those with symptoms to one of 24
      defined priority foods were tested for sIgE. Participants with a positive case
      history and elevated sIgE were evaluated by double-blind placebo-controlled food
      challenge (DBPCFC). Outpatients with a suspicion of FA were evaluated by
      questionnaire, sIgE and DBPCFC. RESULTS: In the community, severe symptoms were
      reported less often than in outpatients (39.3% vs. 54.3%). Participants in the
      community were less commonly sensitized to any of the foods. When selecting only
      those with a probable FA (i.e. symptoms of priority food and elevation of sIgE to
      the respective food), no major differences were observed with respect to
      severity, causative foods, sensitization and DBPCFC between the groups.
      CONCLUSION: In the Netherlands, there are large differences in self-reported FA
      between community and outpatients. However, Dutch community and outpatients with
      a probable FA do not differ with respect to severity, causative foods,
      sensitization and DBPCFC-outcome.

PMID- 25774289
TI  - Langevin dynamics simulations of charged model phosphatidylinositol lipids in the
      presence of diffusion barriers: toward an atomic level understanding of
      corralling of PIP2 by protein fences in biological membranes.
AB  - BACKGROUND: The polyvalent acidic lipid phosphatidylinositol, 4,5-bisphosphate
      (PIP2) is important for many cellular functions. It has been suggested that
      different pools of PIP2 exist in the cytoplasmic leaflet of the plasma membrane,
      and that such pooling could play a role in the regulation of PIP2. The mechanism
      of fencing, however, is not understood. RESULTS: This study presents the results
      of Langevin dynamics simulations of PIP2 to elucidate some of the molecular level
      considerations that must be applied to models for fencing. For each simulation, a
      pool of PIP2 (modeled as charged spheres) was placed in containments with
      boundaries modeled as a single row of rods (steric or electrostatic) or rigid
      protein filaments. It is shown that even a small gap (20 A, which is 1.85 times
      larger than the diameter of a PIP2 sphere) leads to poor steric blocking, and
      that electrostatic blockage is only effective at very high charge density.
      Filaments of human septin, yeast septin, and actin also failed to provide
      adequate blockage when placed on the membrane surface. The two septins do provide
      high blockage consistent with experiment and with phenomenological considerations
      of permeability when they are buried 9 A and 12 A below the membrane surface,
      respectively. In contrast, burial does not improve blockage by the "arch-shaped"
      actin filaments. Free energy estimates using implicit membrane-solvent models
      indicate that burial of the septins to about 10 A can be achieved without
      penetration of charged residues into the hydrophobic region of the membrane.
      CONCLUSIONS: These results imply that a functioning fence assembled from protein
      filaments must either be buried well below the membrane surface, have more than a
      single row, or contain additional components that fill small gaps in the
      filaments.

PMID- 25774291
TI  - Essential oil and aromatic plants as feed additives in non-ruminant nutrition: a
      review.
AB  - This paper summarizes the current knowledge regarding the possible modes of
      action and nutritional factors involved in the use of essential oils (EOs) for
      swine and poultry. EOs have recently attracted increased interest as feed
      additives to be fed to swine and poultry, possibly replacing the use of
      antibiotic growth promoters which have been prohibited in the European Union
      since 2006. In general, EOs enhance the production of digestive secretions and
      nutrient absorption, reduce pathogenic stress in the gut, exert antioxidant
      properties and reinforce the animal's immune status, which help to explain the
      enhanced performance observed in swine and poultry. However, the mechanisms
      involved in causing this growth promotion are far from being elucidated, since
      data on the complex gut ecosystem, gut function, in vivo oxidative status and
      immune system are still lacking. In addition, limited information is available
      regarding the interaction between EOs and feed ingredients or other feed
      additives (especially pro- or prebiotics and organic acids). This knowledge may
      help feed formulators to better utilize EOs when they formulate diets for poultry
      and swine. 

PMID- 25774290
TI  - Transcriptome responses to heat stress in hypothalamus of a meat-type chicken.
AB  - BACKGROUND: Heat stress has resulted in great losses in poultry production. To
      address this issue, we systematically analyzed chicken hypothalamus transcriptome
      responses to thermal stress using a 44 k chicken Agilent microarray. METHODS:
      Hypothalamus samples were collected from a control group reared at 25 degrees C,
      a heat-stress group treated at 34 degrees C for 24 h, and a temperature-recovery
      group reared at 25 degrees C for 24 h following a heat-stress treatment. We
      compared the expression profiles between each pair of the three groups using
      microarray data. RESULTS: A total of 1,967 probe sets were found to be
      differentially expressed in the three comparisons with P < 0.05 and a fold change
      (FC) higher than 1.5, and the genes were mainly involved in self-regulation and
      compensation required to maintain homeostasis. Consistent expression results were
      found for 11 selected genes by quantitative real-time PCR. Thirty-eight
      interesting differential expression genes were found from GO term annotation and
      those genes were related to meat quality, growth, and crucial enzymes. Using
      these genes for genetic network analysis, we obtained three genetic networks.
      Moreover, the transcripts of heat-shock protein, including Hsp 40 and Hsp 90,
      were significantly altered in response to thermal stress. CONCLUSIONS: This study
      provides a broader understanding of molecular mechanisms underlying stress
      response in chickens and discovery of novel genes that are regulated in a
      specific thermal-stress manner.

PMID- 25774292
TI  - Developmental programming: the role of growth hormone.
AB  - Developmental programming of the fetus has consequences for physiologic responses
      in the offspring as an adult and, more recently, is implicated in the expression
      of altered phenotypes of future generations. Some phenotypes, such as fertility,
      bone strength, and adiposity are highly relevant to food animal production and in
      utero factors that impinge on those traits are vital to understand. A key
      systemic regulatory hormone is growth hormone (GH), which has a developmental
      role in virtually all tissues and organs. This review catalogs the impact of GH
      on tissue programming and how perturbations early in development influence GH
      function. 

PMID- 25774293
TI  - BioMiCo: a supervised Bayesian model for inference of microbial community
      structure.
AB  - BACKGROUND: Microbiome samples often represent mixtures of communities, where
      each community is composed of overlapping assemblages of species. Such mixtures
      are complex, the number of species is huge and abundance information for many
      species is often sparse. Classical methods have a limited value for identifying
      complex features within such data. RESULTS: Here, we describe a novel
      hierarchical model for Bayesian inference of microbial communities (BioMiCo). The
      model takes abundance data derived from environmental DNA, and models the
      composition of each sample by a two-level hierarchy of mixture distributions
      constrained by Dirichlet priors. BioMiCo is supervised, using known features for
      samples and appropriate prior constraints to overcome the challenges posed by
      many variables, sparse data, and large numbers of rare species. The model is
      trained on a portion of the data, where it learns how assemblages of species are
      mixed to form communities and how assemblages are related to the known features
      of each sample. Training yields a model that can predict the features of new
      samples. We used BioMiCo to build models for three serially sampled datasets and
      tested their predictive accuracy across different time points. The first model
      was trained to predict both body site (hand, mouth, and gut) and individual human
      host. It was able to reliably distinguish these features across different time
      points. The second was trained on vaginal microbiomes to predict both the Nugent
      score and individual human host. We found that women having normal and elevated
      Nugent scores had distinct microbiome structures that persisted over time, with
      additional structure within women having elevated scores. The third was trained
      for the purpose of assessing seasonal transitions in a coastal bacterial
      community. Application of this model to a high-resolution time series permitted
      us to track the rate and time of community succession and accurately predict
      known ecosystem-level events. CONCLUSION: BioMiCo provides a framework for
      learning the structure of microbial communities and for making predictions based
      on microbial assemblages. By training on carefully chosen features (abiotic or
      biotic), BioMiCo can be used to understand and predict transitions between
      complex communities composed of hundreds of microbial species.

PMID- 25774294
TI  - Being human is a gut feeling.
AB  - Some metagenomic studies have suggested that less than 10% of the cells that
      comprise our bodies are Homo sapiens cells. The remaining 90% are bacterial
      cells. The description of this so-called human microbiome is of great interest
      and importance for several reasons. For one, it helps us redefine what a
      biological individual is. We suggest that a human individual is now best
      described as a super-individual in which a large number of different species
      (including Homo sapiens) coexist. New concepts of biological individuality must
      extend beyond the traditional limitations of our own skin to include our resident
      microbes. Besides its important contributions to science, microbiome research
      raises philosophical questions that strike close to home. What is left of Homo
      sapiens? If most of our cells are not Homo sapiens cells, what does it mean to be
      an individual human being? In this paper, we argue that the biological individual
      is determined by the amount of functional integration among its constitutive
      parts, a definition that applies perfectly to Homo sapiens and its microbiome. 

PMID- 25774295
TI  - Infectious mononucleosis.
AB  - Infectious mononucleosis is a clinical entity characterized by pharyngitis,
      cervical lymph node enlargement, fatigue and fever, which results most often from
      a primary Epstein-Barr virus (EBV) infection. EBV, a lymphocrytovirus and a
      member of the gamma-herpesvirus family, infects at least 90% of the population
      worldwide, the majority of whom have no recognizable illness. The virus is spread
      by intimate oral contact among adolescents, but how preadolescents acquire the
      virus is not known. During the incubation period of approximately 6 weeks, viral
      replication first occurs in the oropharynx followed by viremia as early as 2
      weeks before onset of illness. The acute illness is marked by high viral loads in
      both the oral cavity and blood accompanied by the production of immunoglobulin M
      antibodies against EBV viral capsid antigen and an extraordinary expansion of
      CD8(+) T lymphocytes directed against EBV-infected B cells. During convalescence,
      CD8(+) T cells return to normal levels and antibodies develop against EBV nuclear
      antigen-1. A typical clinical picture in an adolescent or young adult with a
      positive heterophile test is usually sufficient to make the diagnosis of
      infectious mononucleosis, but heterophile antibodies are not specific and do not
      develop in some patients especially young children. EBV-specific antibody
      profiles are the best choice for staging EBV infection. In addition to causing
      acute illness, long-term consequences are linked to infectious mononucleosis,
      especially Hodgkin lymphoma and multiple sclerosis. There is no licensed vaccine
      for prevention and no specific approved treatment. Future research goals are
      development of an EBV vaccine, understanding the risk factors for severity of the
      acute illness and likelihood of developing cancer or autoimmune diseases, and
      discovering anti-EBV drugs to treat infectious mononucleosis and other EBV
      spurred diseases. 

PMID- 25774296
TI  - Orthorexia nervosa and self-attitudinal aspects of body image in female and male
      university students.
AB  - BACKGROUND: The present study was designed to investigate orthorexia nervosa, or
      the phenomenon of being preoccupied with consuming healthy food. Specific aims
      were to explore relationships between orthorexia features and attitudes towards
      body image, fitness and health in normal weight female and male university
      students with high levels of healthy food preoccupation, i.e. orthorexia nervosa.
      METHODS: Participants were 327 female (N = 283) and male (N = 44) students aged
      18 to 25 years. All participants completed the Polish adaptation of the 15-item
      questionnaire assessing orthorexia eating behaviours (the ORTHO-15) and the
      Multidimensional Body-Self Relations Questionnaire (the MBSRQ). Relationships
      between scores on the ORTHO-15 and MBSRQ were explored in the 213 students who
      had high levels of preoccupation with a healthy food intake (68.55% women and
      43.18% men, respectively). RESULTS: There were no statistically significant
      differences in the levels of orthorexia behaviours between females and males. In
      female students with orthorexia nervosa, preoccupation with consuming healthy
      food was significantly correlated with the MBSRQ subscale scores for overweight
      preoccupation, appearance orientation, fitness orientation, health orientation,
      body areas satisfaction and appearance evaluation. Conversely, in male students
      with orthorexia nervosa there were no correlations between orthorexic behaviours
      and the MBSRQ subscales. In female students with orthorexia nervosa multivariable
      linear regression analysis found high body areas (parts) satisfaction, low
      fitness orientation, low overweight preoccupation and low appearance orientation
      were independent predictors of greater fixation on eating healthy food. In male
      students, we found that aspects of body image were not associated with
      preoccupation with healthy eating. CONCLUSION: A strong preoccupation with
      healthy and proper food was not associated with an unhealthy body-self
      relationship among Polish female student with orthorexia nervosa.

PMID- 25774297
TI  - Who do you think you are? - Personality in eating disordered patients.
AB  - BACKGROUND: The Five-Factor Model of personality is strongly linked to common
      mental disorders. Yet the relationship between the lower order personality traits
      (facets) of the model and eating disorder (ED) features remains unclear. The aim
      of the study was to explore how patients with non-anorexic ED differ from
      controls in personality and to examine the ability of personality facets to
      explain psychopathology. METHODS: Female patients with non-anorexic ED (N = 208)
      were assessed on general psychopathology, ED symptoms and personality as measured
      by the NEO PI-R; and were compared on personality to age-matched female controls
      (N = 94). RESULTS: Compared to controls, patients were characterised by
      experiencing pervasive negative affectivity and vulnerability, with little in the
      way of positive emotions such as joy, warmth and love. Patients were also
      significantly less warm and sociable, and exhibited less trust, competence, and
      self-discipline. Finally, they were less open to feelings, ideas and new
      experiences, yet more open in their values. Among patients, personality facets
      explained up to 25% of the variance in ED and general psychopathology.
      CONCLUSIONS: ED patients have distinct patterns of personality. Identifying and
      focusing on personality traits may aid in understanding ED, help therapists
      enhance the treatment alliance, address underlying problems, and improve outcome.

PMID- 25774298
TI  - Development and validation of parenting measures for body image and eating
      patterns in childhood.
AB  - BACKGROUND: Evidence-based parenting interventions are important in assisting
      parents to help their children develop healthy body image and eating patterns. To
      adequately assess the impact of parenting interventions, valid parent measures
      are required. The aim of this study was to develop and assess the validity and
      reliability of two new parent measures, the Parenting Intentions for Body image
      and Eating patterns in Childhood (Parenting Intentions BEC) and the Knowledge
      Test for Body image and Eating patterns in Childhood (Knowledge Test BEC).
      METHODS: Participants were 27 professionals working in research or clinical
      treatment of body dissatisfaction or eating disorders, and 75 parents of children
      aged 2-6 years, who completed the measures via an online questionnaire. Seven
      scenarios were developed for the Parenting Intentions BEC to describe common
      experiences about the body and food that parents might need to respond to in
      front of their child. Parents ranked four behavioural intentions, derived from
      the current literature on parenting risk factors for body dissatisfaction and
      unhealthy eating patterns in children. Two subscales were created, one
      representing positive behavioural intentions, the other negative behavioural
      intentions. After piloting a larger pool of items, 13 statements were used to
      construct the Knowledge Test BEC. These were designed to be factual statements
      about the influence of parent language, media, family meals, healthy eating, and
      self-esteem on child eating and body image. The validity of both measures was
      tested by comparing parent and professional scores, and reliability was assessed
      by comparing parent scores over two testing occasions. RESULTS: Compared with
      parents, professionals reported significantly higher scores on the Positive
      Intentions subscale and significantly lower on the Negative Intentions subscale
      of the Parenting Intentions BEC; confirming the discriminant validity of six out
      of the seven scenarios. Test-retest reliability was also confirmed as parent
      scores on the two Parenting Intentions subscales did not differ over time. Eleven
      out of the 13 Knowledge Test items demonstrated sufficient discriminant validity
      and test-retest reliability. CONCLUSIONS: Overall, results indicated that the six
      scenario Parenting Intentions BEC and the 11-item Knowledge Test BEC are valid
      and reliable measures for parents of young children.

PMID- 25774299
TI  - Basic and clinical assessment of initial distribution volume of glucose in
      hemodynamically stable pediatric intensive care patients.
AB  - BACKGROUND: Initial distribution volume of glucose (IDVG), which is not
      associated with significant modification of glucose metabolism, has been proposed
      as an indicator of the central extracellular fluid volume status in adults.
      However, data on IDVG in children are lacking. This study examined
      pharmacokinetic data on IDVG in children and compared IDVG with other clinical
      variables. METHODS: In total, 128 daily data sets from 60 consecutive pediatric
      intensive care patients (body weight >=8.0 kg), consisting mostly of children
      undergoing cardiovascular surgery, were studied. Either 1 or 2 g of glucose based
      on body weight (approximately 0.1 g/kg) was administered. IDVG could not be
      determined from ten data sets from eight children because of body movement
      associated glucose fluctuation during measurement. In the remaining 113 data sets
      from 55 children, IDVG was determined by applying the one-compartment model.
      Approximated IDVG based on the incremental plasma glucose level at 3 min
      postinjection (1-point IDVG), and approximated IDVG based on incremental plasma
      glucose levels at 3 and 5 min postinjection (2-point IDVG), were also calculated.
      Postoperative daily IDVG and the relationship between IDVG and cardiac output or
      circulating blood volume (CBV) were evaluated when data were available. RESULTS:
      Convergence was assumed in each glucose clearance curve. Mean indexed IDVG
      (IDVGI) of the first measurement in 55 children was 144 +/- 22 (SD) mL/kg, which
      was associated with a plasma glucose disappearance rate (Ke-glucose) of 0.094 +/-
      0.033/min. Bias and precision were smaller between 2-point IDVG and standard IDVG
      than between 1-point IDVG and standard IDVG (-0.02 +/- 0.13 L versus 0.07 +/-
      0.20 L, p <0.001). Postoperative IDVGI in 37 children after cardiovascular
      surgery increased daily on postoperative days 1-2 (p <=0.011). Linear
      correlations were observed between IDVGI and indexed cardiac output (r = 0.588, n
      = 28, p <0.001) and between IDVGI and indexed CBV (r = 0.547, n = 25, p =
      0.0047). CONCLUSIONS: IDVG is a potential marker of fluid volume status in
      children, even though body movement-associated glucose fluctuation is a major
      limitation. Two-point IDVG is preferable to 1-point IDVG for approximated IDVG.

PMID- 25774300
TI  - Single coronary artery originating from the right sinus Valsalva and ability to
      work.
AB  - We present a case of a 56-year-old male electrician who was admitted to the
      hospital with atrial fibrillation, atypical chest pain and dyspnea. He gave a
      history that on the morning he had working for almost 4 hours carrying out
      various activities with considerable physical effort. After cardioversion,
      conventional coronary angiography revealed a suspect of single coronary vessel
      (SCA) arising from the right sinus of Valsalva. The patient underwent multislice
      computed tomography that showed a SCA arising from the right sinus Valsalva and
      dividing in Right Coronary Artery (RCA) and Left Main coronary artery (LM). The
      finding of posterior course of the LM without atherosclerotic has proved crucial
      for the expression of an opinion of working capacity even with limitation. 

PMID- 25774301
TI  - Thoracocentesis: from bench to bed.
AB  - Lung cancer can be diagnosed with minimal interventional procedures such as:
      bronchoscopy, endobronchial ultrasound (EBUS), fine needle aspiration under CT
      guidance and esophageal ultrasound. In our current editorial we will provide a
      definition and current up to date information regarding fine needle aspiration
      under CT guidance. We will focus on pneumothorax and treatment methods. 

PMID- 25774302
TI  - Estimating the direct and indirect costs of lung cancer: a prospective analysis
      in a Greek University Pulmonary Department.
AB  - BACKGROUND: Lung cancer (LC) is a disease with high morbidity and mortality while
      the prevention and treatment constitutes a significant financial burden. This
      economic burden has an increasing trend, with hospitalization being the highest
      cost factor in most studies, while the patients' quality of life (QoL) and
      response to treatment is not proven to be positively affected. OBJECTIVE: To
      evaluate the direct and indirect cost of managing patients with LC in Greece
      according to stage and histological type of cancer, total chemotherapy cycles,
      age, gender, smoking habit, overall survival (OS), treatment outcome (TO) and
      QoL. METHODS: One hundred thirteen of 128 consecutive patients met the inclusion
      criteria and were included in this prospective study. Patient enrolment started
      in August 2011 and ended in November 2011. The duration of the patient follow up
      was 32 months after diagnosis until end of registry. Total direct cost included
      diagnosis and treatment cost. Indirect cost constituted of patient's and family
      caregivers lost days of productivity. QoL was assessed with EORTC-QLQ-30 and Lung
      Cancer Symptom Scale (LCSS) questionnaires before treatment and every three
      months. RESULTS: Total direct cost was ?1,853,984 and chemotherapy drugs was the
      highest cost factor (?1,216,421). Total indirect cost was 28,774 days of which
      27,293 were related to patients. Total direct cost was significantly related to
      the increased number of total chemotherapy cycles, longer OS, histological type
      of adenocarcinoma, female gender and younger patients. No relation was found
      between total indirect cost and the above factors. When the association between
      total direct/indirect cost and QoL was examined no significant results were
      drawn. CONCLUSIONS: The burden of LC on health care systems remains very high and
      was associated with the increased number of total chemotherapy cycles, longer OS,
      adenocarcinoma histological type of cancer, female gender and younger patients.
      Chemotherapy drugs constituted the higher factor of total direct cost. Indirect
      cost was considerably higher for patients than family caregivers and did not
      significantly differ in relation to the above factors. No significant conclusion
      was drawn regarding QoL and total direct/indirect cost.

PMID- 25774303
TI  - Repair of post-intubation tracheoesophageal fistulae through the left pre
      sternocleidomastoid approach: a recent case series of 13 patients.
AB  - OBJECTIVE: Post-intubation tracheoesophageal fistula (TEF) is a late complication
      of tracheotomy, while membranous trachea laceration during percutaneous
      dilational tracheostomy is implicated in the generation of early post-tracheotomy
      TEF. Surgical repair is the only viable option for these patients and the
      technique of repair depends on a variety of factors. METHODS: Totally 13 patients
      (mean age: 54.1+/-12.6 years; male: 8) with post-intubation TEF were managed
      between 2007 and 2013. The diagnosis was always made through esophagoscopy
      followed by endoscopic gastrostomy and bronchoscopy for repositioning of the
      tracheal tube just above the carina. Repair of the fistula was made in all
      patients through a left pre-sternocleidomastoid incision followed by dissection
      of the fistulous tract, suturing of esophagus and trachea and interposition of
      the whole pedicled left sternocleidomastoid muscle (SCMM) between the two suture
      lines. RESULTS: Five out of the 13 procedures were performed in mechanically
      ventilated patients; 3 of them died from septic complications during the
      postoperative period while fistula recurred in 1 of those 3 patients due to
      extensive inflammation of the tracheal wall. The rest 8 patients underwent
      fistula repair after weaning from mechanical ventilation and the results of
      repair were excellent. The additional procedure of temporary T-tube insertion was
      obviated in one patient to manage extensive tracheomalacia. CONCLUSIONS: The left
      pre-sternocleidomastoid incision is an excellent access for the repair of a post
      intubation TEF without tracheal resection. The interposition of the whole left
      pedicled SCMM between the suture lines of trachea and esophagus avoids fistula
      recurrence and offers the best chance for cure.

PMID- 25774304
TI  - Pleura space anatomy.
AB  - The pleural cavity is the potential space between the two pleurae (visceral and
      parietal) of the lungs. The pleurae are serous membranes which fold back onto
      themselves to form a two-layered membranous structure. The thin space between the
      two pleural layers is known as the pleural cavity and normally contains a small
      amount of pleural fluid. There are two layers; the outer pleura (parietal pleura)
      is attached to the chest wall and the inner pleura (visceral pleura) covers the
      lungs and adjoining structures, via blood vessels, bronchi and nerves. The
      parietal pleurae are highly sensitive to pain, while the visceral pleura are not,
      due to its lack of sensory innervation. In the current review we will present the
      anatomy of the pleural space. 

PMID- 25774305
TI  - Physiology of the pleural space.
AB  - The pleural cavity is created between the 4(th) and 7(th) week of embryologic
      development. These embryonic components of visceral and parietal pleurae develop
      different anatomic characteristics with regard to vascular, lymphatic, and
      nervous supply. There are two layers: a superficial mesothelial cell layer facing
      the pleural space and an underlying connective tissue layer. The pleura might
      present inflammatory response and maintenance of the pleural fluid is observed.
      The latter function is especially important in the mechanical coupling of the
      lung and chest wall. Fluid is filtered into the pleural space according to the
      net hydrostatic oncotic pressure gradient. It flows downward along a vertical
      pressure gradient, presumably determined by hydrostatic pressure and resistance
      to viscous flow. There also may be a net movement of fluid from the costal pleura
      to the mediastinal and interlobar regions. In these areas, pleural fluid is
      resorbed primarily through lymphatic stomata on the parietal pleural surface. In
      the current review we will present the physiology of the pleural space in a step
      by step manner. 

PMID- 25774306
TI  - Barotrauma and pneumothorax.
AB  - Barotrauma is physical damage to body tissues caused by a difference in pressure
      between a gas space inside, or in contact with the body, and the surrounding
      fluid. This situation typically occurs when the organism is exposed to a
      significant change in ambient pressure, such as when a scuba diver, a free-diver
      or an airplane passenger ascends or descends, or during uncontrolled
      decompression of a pressure vessel, but it can also happen by a shock wave.
      Whales and dolphins are also vulnerable to barotrauma if exposed to rapid and
      excessive changes in diving pressures. In the current review we will focus on
      barotraumas from definition to treatment. 

PMID- 25774307
TI  - Pneumomediastinum.
AB  - Pneumomediastinum is a condition in which air is present in the mediastinum. This
      condition can result from physical trauma or other situations that lead to air
      escaping from the lungs, airways or bowel into the chest cavity.
      Pneumomediastinum is a rare situation and occurs when air leaks into the
      mediastinum. The diagnosis can be confirmed via chest X-ray or CT scanning of the
      thorax. The main symptom is usually severe central chest pain. Other symptoms
      include laboured breathing, voice distortion (as with helium) and subcutaneous
      emphysema, specifically affecting the face, neck, and chest. Pneumomediastinum
      can also be characterized by the shortness of breath that is typical of a
      respiratory system problem. It is often recognized on auscultation by a
      "crunching" sound timed with the cardiac cycle (Hamman's crunch).
      Pnemomediastinum may also present with symptoms mimicking cardiac tamponade as a
      result of the increased intrapulmonary pressure on venous flow to the heart. The
      tissues in the mediastinum will slowly resorb the air in the cavity so most
      pneumomediastinums are treated conservatively. 

PMID- 25774308
TI  - Semi-Fowler vs. lateral decubitus position for thoracoscopic sympathectomy in
      treatment of primary focal hyperhidrosis.
AB  - BACKGROUND AND OBJECTIVE: The aim of this study is to compare usefulness of Semi
      Fowler position vs. lateral decubitus position for thoracoscopic sympathectomy in
      treatment of primary focal hyperhidrosis. MATERIALS AND METHODS: From January
      2009 to January 2010, 263 consecutive patients with palmar and axillar
      hyperhidrosis underwent thoracoscopic sympathectomy Th2-Th4. Patients were
      divided into two groups: group A (n=133) underwent thoracoscopic sympathectomy
      through lateral decubitus using double lumen endotracheal intubation, and group B
      (n=130) underwent thoracoscopic sympathectomy through Semi-Fowler supine position
      (semi sitting with arm abducted) using single lumen endotracheal intubation
      without insufflation of CO2, but with short apnea period. All operations were
      performed through two 5 mm operating ports, videothoracoscopic camera 0 degrees 
      and endoscopic ultrasound activated harmonic scalpel. RESULTS: There were 107
      males and 156 females with median age 30.31+/-8.35 years. Two groups were
      comparable in gender, age, severity of sweating. All operations were successfully
      performed with no complications or perioperative morbidity. For group A average
      operation time for both sides was 31.2+/-3.87 min and for group B average time
      was 14.19+/-4.98 min. In group B apnea period per one lung lasts 2.86+/-1.15 min
      and during that period observed saturation was 92.65%+/-5.66% without significant
      cardiorespiratory disturbances. Pleural drains were taken off on operation table
      after forced manually lung reexpansion. Patients were discharged from hospital
      for few hours, after the operation and radiologic confirmation of complete lung
      reexpansion. CONCLUSIONS: Based on this data (shorter operating time, lack of
      incomplete lung collapse, insignificant apnea and better reexpansion of lungs) we
      concluded that thoracoscopic sympathectomy through Semi-Fowler supine position is
      highly effective and easy to perform for primary hyperhidrosis.

PMID- 25774309
TI  - Open thoracotomy for pneumothorax.
AB  - A thoracotomy is an incision into the pleural space of the chest. It is performed
      by surgeons (or emergency physicians under certain circumstances) to gain access
      to the thoracic organs, most commonly the heart, the lungs, or the esophagus, or
      for access to the thoracic aorta or the anterior spine. This surgical procedure
      is a major surgical maneuver it is the first step in many thoracic surgeries
      including lobectomy or pneumonectomy for lung cancer and as such requires general
      anesthesia with endotracheal tube insertion and mechanical ventilation, rigid
      bronchoscope can be also used if necessary. Thoracotomies are thought to be one
      of the most difficult surgical incisions to deal with post-operatively, because
      they are extremely painful and the pain can prevent the patient from breathing
      effectively, leading to atelectasis or pneumonia. In the current review we will
      present the steps of this procedure. 

PMID- 25774310
TI  - Video-assisted thoracic surgery and pneumothorax.
AB  - Video-assisted thoracoscopic surgery (VATS) is a type of thoracic surgery
      performed using a small video camera that is introduced into the patient's chest
      via a scope. It is considered a minimally invasive technique where the surgeon is
      able to view the instruments that are being used along with the anatomy on which
      the surgeon is operating. The camera and instruments are inserted through
      separate holes in the chest wall also known as "ports", depending on the patient
      and problem there are surgeries with one port "uniport", two or three ports.
      These small ports have the advantage that fewer infections are observed. This
      allows for a faster recovery. Traditionally, thoracic surgery performed for
      diagnosis or treatment of chest conditions has required access to the chest
      through thoracotomy or sternotomy incisions. Vats minimally invasive technique
      has replaced in many cases thoracotomy or sternotomy. In our current review we
      will present this technique in detail. 

PMID- 25774312
TI  - Dr. Paul Zarogoulidis: the exploration on pneumothorax and new use of EBUS.

PMID- 25774311
TI  - Postoperative pain management.
AB  - Postoperative pain is a very important issue for several patients. Indifferent of
      the surgery type or method, pain management is very necessary. The relief from
      suffering leads to early mobilization, less hospital stay, reduced hospital
      costs, and increased patient satisfaction. An individual approach should be
      applied for pain control, rather than a fix dose or drugs. Additionally, medical,
      psychological, and physical condition, age, level of fear or anxiety, surgical
      procedure, personal preference, and response to agents given should be taken into
      account. The major goal in the management of postoperative pain is minimizing the
      dose of medications to lessen side effects while still providing adequate
      analgesia. Again a multidisciplinary team approach should be pursued planning and
      formulating a plan for pain relief, particularly in complicated patients, such as
      those who have medical comorbidities. These patients might appear increase for
      analgesia-related complications or side effects. 

PMID- 25774314
TI  - A case of true hermaphroditism presenting as a testicular tumour.
AB  - True hermaphroditism represents only 5% cases of all of disorders of sexual
      differentiation (DSD) and usually present in early childhood with ambiguous
      genitalia. Occasionally, cases might present later on in adolescence with
      problems of sexual maturation. Our case report presents a true hermaphrodite with
      normal male phenotype that presented as a left testicular mass, two years after
      being diagnosed with Sertoli cell only syndrome in the contralateral testis.
      Histological examination of the left testis showed ovarian, fallopian tube,
      myometrial, endometrial, and epididymal tissue. This combination of findings is
      found in approximately one-third of true hermaphrodites, but it is very rare to
      present clinically as an inguinoscrotal mass. 

PMID- 25774315
TI  - Evaluating whole slide imaging: A working group opportunity.

PMID- 25774313
TI  - Fundus Autofluorescence and RPE Lipofuscin in Age-Related Macular Degeneration.
AB  - Genes that increase susceptibility to age-related macular degeneration (AMD) have
      been identified; however, since many individuals carrying these risk alleles do
      not develop disease, other contributors are involved. One additional factor, long
      implicated in the pathogenesis of AMD, is the lipofuscin of retinal pigment
      epithelium (RPE). The fluorophores that constitute RPE lipofuscin also serve as a
      source of autofluorescence (AF) that can be imaged by confocal laser
      ophthalmoscopy. The AF originating from lipofuscin is excited by the delivery of
      short wavelength (SW) light. A second autofluorescence is emitted from the
      melanin of RPE (and choroid) upon near-infrared (NIR-AF) excitation. SW-AF
      imaging is currently used in the clinical management of retinal disorders and the
      advantages of NIR-AF are increasingly recognized. Here we visit the damaging
      properties of RPE lipofuscin that could be significant when expressed on a
      background of genetic susceptibility. To advance interpretations of disease
      related patterns of fundus AF in AMD, we also consider the photochemical and
      spectrophotometric features of the lipofuscin compounds responsible for
      generating the fluorescence emission. 

PMID- 25774316
TI  - Summary of 2(nd) Nordic symposium on digital pathology.
AB  - Techniques for digital pathology are envisioned to provide great benefits in
      clinical practice, but experiences also show that solutions must be carefully
      crafted. The Nordic countries are far along the path toward the use of whole
      slide imaging in clinical routine. The Nordic Symposium on Digital Pathology
      (NDP) was created to promote knowledge exchange in this area, between
      stakeholders in health care, industry, and academia. This article is a summary of
      the NDP 2014 symposium, including conclusions from a workshop on clinical
      adoption of digital pathology among the 144 attendees. 

PMID- 25774317
TI  - Histopathology in 3D: From three-dimensional reconstruction to multi-stain and
      multi-modal analysis.
AB  - Light microscopy applied to the domain of histopathology has traditionally been a
      two-dimensional imaging modality. Several authors, including the authors of this
      work, have extended the use of digital microscopy to three dimensions by stacking
      digital images of serial sections using image-based registration. In this paper,
      we give an overview of our approach, and of extensions to the approach to
      register multi-modal data sets such as sets of interleaved histopathology
      sections with different stains, and sets of histopathology images to radiology
      volumes with very different appearance. Our approach involves transforming
      dissimilar images into a multi-channel representation derived from co-occurrence
      statistics between roughly aligned images. 

PMID- 25774318
TI  - A comparative study of input devices for digital slide navigation.
AB  - This paper describes work presented at the Nordic Symposium on Digital Pathology
      2014, Linkoping, Sweden. Quick and seamless integration between input devices and
      the navigation of digital slides remains a key barrier for many pathologists to
      "go digital." To better understand this integration, three different input device
      implementations were compared in terms of time to diagnose, perceived workload
      and users' preferences. Six pathologists reviewed in total nine cases with a
      computer mouse, a 6 degrees-of-freedom (6DOF) navigator and a touchpad. The
      participants perceived significantly less workload (P < 0.05) with the computer
      mouse and the 6DOF navigator, than with the touchpad, while no effect of the
      input device used on the time to diagnose was observed. Five out of six
      pathologists preferred the 6DOF navigator, while the touchpad was the least
      preferred device. While digital slide navigation is often designed to mimic
      microscope interaction, the results of this study demonstrate that in order to
      minimize workload there is reason to let the digital interaction move beyond the
      familiar microscope tradition. 

PMID- 25774319
TI  - RandomSpot: A web-based tool for systematic random sampling of virtual slides.
AB  - This paper describes work presented at the Nordic Symposium on Digital Pathology
      2014, Linkoping, Sweden. Systematic random sampling (SRS) is a stereological
      tool, which provides a framework to quickly build an accurate estimation of the
      distribution of objects or classes within an image, whilst minimizing the number
      of observations required. RandomSpot is a web-based tool for SRS in stereology,
      which systematically places equidistant points within a given region of interest
      on a virtual slide. Each point can then be visually inspected by a pathologist in
      order to generate an unbiased sample of the distribution of classes within the
      tissue. Further measurements can then be derived from the distribution, such as
      the ratio of tumor to stroma. RandomSpot replicates the fundamental principle of
      traditional light microscope grid-shaped graticules, with the added benefits
      associated with virtual slides, such as facilitated collaboration and automated
      navigation between points. Once the sample points have been added to the
      region(s) of interest, users can download the annotations and view them locally
      using their virtual slide viewing software. Since its introduction, RandomSpot
      has been used extensively for international collaborative projects, clinical
      trials and independent research projects. So far, the system has been used to
      generate over 21,000 sample sets, and has been used to generate data for use in
      multiple publications, identifying significant new prognostic markers in
      colorectal, upper gastro-intestinal and breast cancer. Data generated using
      RandomSpot also has significant value for training image analysis algorithms
      using sample point coordinates and pathologist classifications. 

PMID- 25774320
TI  - Clinical laboratory analytics: Challenges and promise for an emerging discipline.
AB  - The clinical laboratory is a major source of health care data. Increasingly these
      data are being integrated with other data to inform health system-wide actions
      meant to improve diagnostic test utilization, service efficiency, and "meaningful
      use." The Academy of Clinical Laboratory Physicians and Scientists hosted a
      satellite meeting on clinical laboratory analytics in conjunction with their
      annual meeting on May 29, 2014 in San Francisco. There were 80 registrants for
      the clinical laboratory analytics meeting. The meeting featured short
      presentations on current trends in clinical laboratory analytics and several
      panel discussions on data science in laboratory medicine, laboratory data and its
      role in the larger healthcare system, integrating laboratory analytics, and data
      sharing for collaborative analytics. One main goal of meeting was to have an open
      forum of leaders that work with the "big data" clinical laboratories produce.
      This article summarizes the proceedings of the meeting and content discussed. 

PMID- 25774321
TI  - A bayesian approach to laboratory utilization management.
AB  - BACKGROUND: Laboratory utilization management describes a process designed to
      increase healthcare value by altering requests for laboratory services. A typical
      approach to monitor and prioritize interventions involves audits of laboratory
      orders against specific criteria, defined as rule-based laboratory utilization
      management. This approach has inherent limitations. First, rules are inflexible.
      They adapt poorly to the ambiguity of medical decision-making. Second, rules
      judge the context of a decision instead of the patient outcome allowing an order
      to simultaneously save a life and break a rule. Third, rules can threaten
      physician autonomy when used in a performance evaluation. METHODS: We developed
      an alternative to rule-based laboratory utilization. The core idea comes from a
      formula used in epidemiology to estimate disease prevalence. The equation relates
      four terms: the prevalence of disease, the proportion of positive tests, test
      sensitivity and test specificity. When applied to a laboratory utilization audit,
      the formula estimates the prevalence of disease (pretest probability [PTP]) in
      the patients tested. The comparison of PTPs among different providers, provider
      groups, or patient cohorts produces an objective evaluation of laboratory
      requests. We demonstrate the model in a review of tests for enterovirus (EV)
      meningitis. RESULTS: The model identified subpopulations within the cohort with a
      low prevalence of disease. These low prevalence groups shared demographic and
      seasonal factors known to protect against EV meningitis. This suggests too many
      orders occurred from patients at low risk for EV. CONCLUSION: We introduce a new
      method for laboratory utilization management programs to audit laboratory
      services.

PMID- 25774322
TI  - Performance of the CellaVision((r)) DM96 system for detecting red blood cell
      morphologic abnormalities.
AB  - BACKGROUND: Red blood cell (RBC) analysis is a key feature in the evaluation of
      hematological disorders. The gold standard light microscopy technique has high
      sensitivity, but is a relativity time-consuming and labor intensive procedure.
      This study tested the sensitivity and specificity of gold standard light
      microscopy manual differential to the CellaVision((r)) DM96 (CCS; CellaVision,
      Lund, Sweden) automated image analysis system, which takes digital images of
      samples at high magnification and compares these images with an artificial neural
      network based on a database of cells and preclassified according to RBC
      morphology. METHODS: In this study, 212 abnormal peripheral blood smears within
      the Calgary Laboratory Services network of hospital laboratories were selected
      and assessed for 15 different RBC morphologic abnormalities by manual microscopy.
      The same samples were reassessed as a manual addition from the instrument screen
      using the CellaVision((r)) DM96 system with 8 microscope high power fields (*100
      objective and a 22 mm ocular). The results of the investigation were then used to
      calculate the sensitivity and specificity of the CellaVision((r)) DM96 system in
      reference to light microscopy. RESULTS: The sensitivity ranged from a low of 33%
      (RBC agglutination) to a high of 100% (sickle cells, stomatocytes). The remainder
      of the RBC abnormalities tested somewhere between these two extremes. The
      specificity ranged from 84% (schistocytes) to 99.5% (sickle cells, stomatocytes).
      CONCLUSIONS: Our results showed generally high specificities but variable
      sensitivities for RBC morphologic abnormalities.

PMID- 25774323
TI  - Performance assessment of communicable disease surveillance in disasters: a
      systematic review.
AB  - BACKGROUND: This study aimed to identify the indices and frameworks that have
      been used to assess the performance of communicable disease surveillance (CDS) in
      response to disasters and other emergencies, including infectious disease
      outbreaks. METHOD: In this systematic review, PubMed, Google Scholar, Scopus,
      ScienceDirect, ProQuest databases and grey literature were searched until the end
      of 2013. All retrieved titles were examined in accordance with inclusion
      criteria. Abstracts of the relevant titles were reviewed and eligible abstracts
      were included in a list for data abstraction. Finally, the study variables were
      extracted. RESULTS: Sixteen articles and one book were found relevant to our
      study objectives. In these articles, 31 criteria and 35 indicators were used or
      suggested for the assessment/evaluation of the performance of surveillance
      systems in disasters. The Centers for Disease Control (CDC) updated guidelines
      for the evaluation of public health surveillance systems were the most widely
      used. CONCLUSION: Despite the importance of performance assessment in improving
      CDS in response to disasters, there is a lack of clear and accepted frameworks.
      There is also no agreement on the use of existing criteria and indices. The only
      relevant framework is the CDC guideline, which is a common framework for
      assessing public health surveillance systems as a whole. There is an urgent need
      to develop appropriate frameworks, criteria, and indices for specifically
      assessing the performance of CDS in response to disasters and other emergencies,
      including infectious diseases outbreaks. Key words: Disasters, Emergencies,
      Communicable Diseases, Surveillance System, Performance Assessment.

PMID- 25774324
TI  - Tehran dust storm early warning system: corrective measures.
AB  - On June 2, 2014 a sandstorm hit Tehran, the capital city of Iran which killed 5
      and injured 44 people. The early warning system did not operate properly and the
      alarm was not transferred to at risk population and the related organizations in
      time and in a right manner. Additionally, people who were exposed to the winds
      didn't know the appropriate safety measures. Focusing much more on establishing
      EWS to alert the risk prone population timely and public education for taking
      safety measures when exposed to the disastrous situation is recommended. 

PMID- 25774325
TI  - Chorea associated with high titers of antiphospholipid antibodies in the absence
      of antiphospholipid antibody syndrome.
AB  - BACKGROUND: Chorea associated with high titers of antiphospholipid antibodies in
      the absence of antiphospholipid antibody syndrome has been seldom reported. CASE
      REPORT: An 89-year-old female developed persistent right side chorea associated
      with high titers of anticardiolipin antibody (antiphospholipid antibosies
      immunoglobulin (Ig)M, 45 MPL and 112 IgM aCL (MPL) after 3 months) but normal
      lupus anticoagulants. Her magnetic resonance imaging (MRI) showed no abnormality,
      but positron emission tomography (PET) demonstrated increased bilateral striatal
      metabolic activity, more on the left side. Her MRI showed no cause for chorea.
      The PET scan demonstrated a marked increase in the metabolic activity of the left
      basal ganglia. DISCUSSION: Her chorea remained unchanged over a 9-month follow-up
      period. The literature on chorea associated with high titers of antiphospholipid
      antibodies in the absence of antiphospholipid syndrome is reviewed.

PMID- 25774326
TI  - One-year outcomes of women started on antiretroviral therapy during pregnancy
      before and after the implementation of Option B+ in Malawi: A retrospective chart
      review.
AB  - OBJECTIVE: To compare one-year outcomes of women started on antiretroviral
      therapy (ART) during pregnancy in the pre-Option B+ era to those in the Option B+
      era. METHODS: A retrospective chart review was performed at three sites in
      Malawi. Women were included in the 'pre-Option B+' cohort if they started ART
      during pregnancy for a CD4 count < 350 cells/mm3 or WHO 3/4 condition and in the
      'Option B+' cohort if they started ART during pregnancy regardless of CD4 count
      or clinical stage. One-year outcomes were compared using Fisher's exact and ANOVA
      F-tests. RESULTS: A higher proportion of women in the pre-Option B+ cohort
      started ART at WHO stage 3/4 (11.9% versus 1.1%, P < 0.001), switched ART
      regimens (5.9% versus 0%, P = 0.002), or died in the first year after starting
      treatment (3.9% versus .5%, P = 0.05). While more women in the Option B+ cohort
      had poor adherence or defaulted, these differences were not significant.
      CONCLUSIONS: At our study sites, the transition to Option B+ has been associated
      with ART initiation in women with less advanced HIV infection, improved
      medication tolerability, and lower mortality. Further research is needed to
      better understand outcomes of Option B+.

PMID- 25774327
TI  - Methods of Retinal Ganglion Cell Differentiation From Pluripotent Stem Cells.
AB  - Glaucoma, the worldwide leading cause of irreversible blindness, is characterized
      by progressive degeneration of the optic nerve and loss of retinal ganglion
      cells. Research into glaucoma pathogenesis has been hampered by difficulties in
      isolating and culturing retinal ganglion cells in vitro. However, recent
      improvements in laboratory techniques have enabled the generation of a variety of
      mature cell types from pluripotent stem cells, including retinal ganglion cells.
      Indeed, stem cell-based approaches have the potential to revolutionize the field
      by providing an unlimited source of cells for replacement therapies and by
      enabling development of in vitro disease models for drug screening and research.
      Consequently, research aimed at directing pluripotent stem cells to differentiate
      into retinal ganglion cells has expanded dramatically during the past decade,
      resulting in significant advances in technique and efficiency. In this paper, we
      review the methodology for retinal ganglion cell differentiation from pluripotent
      stem cells of both mouse and human origin and summarize how these techniques have
      opened up new avenues for modelling glaucoma. Generation of stem cell-derived
      retinal ganglion cells will have significant translational values, providing an
      in vitro platform to study the mechanisms responsible for pathogenesis and for
      drug screening to improve treatment options, as well as for the development of
      cell therapies for optic neuropathies such as glaucoma.

PMID- 25774329
TI  - Fixation Stability Measurement Using Two Types of Microperimetry Devices.
AB  - PURPOSE: We compared the fixation stability measurements obtained with two
      microperimeters, the Micro Perimeter 1 (MP-1) and the Spectral OCT/SLO (OCT/SLO),
      in subjects with and without maculopathies. METHODS: A total of 41 eyes with no
      known ocular diseases and 45 eyes with maculopathies were enrolled in the study.
      Both eyes of each participant had a 20-second fixation test using the MP-1 and
      OCT/SLO. The bivariate contour ellipse area (BCEA) was used for fixation
      stability evaluation. RESULTS: In the normal group, BCEA was 2.93 +/- 0.32 log
      minarc2 on OCT/SLO and 2.89 +/- 0.30 log minarc2 on MP-1. In the maculopathy
      group, BCEA was 3.05 +/- 0.41 log minarc2 on OCT/SLO and 3.15 +/- 0.46 log
      minarc2 on MP-1. There was no statistically significant difference between the
      BCEA measured by OCT/SLO and by MP-1 in both groups. A moderate correlation was
      found between the two devices (r = 0.45, P < 0.001). The sample size during the
      fixation test was 535.5 +/- 14.6 pairs of coordinates in the normal group and
      530.7 +/- 14.9 pairs in the maculopathy group with MP-1, while it was 72.3 +/-
      6.9 and 59.9 +/- 10.1, respectively, with OCT/SLO. This was due to different
      tracking frequencies between the two microperimeters. CONCLUSION: Fixation
      stability assessment yields similar results using the OCT/SLO and MP-1. A major
      difference in sampling rate between the two microperimeters does not
      significantly affect BCEA measurements. TRANSLATIONAL RELEVANCE: Fixation
      stability assessments are comparable and interchangeable between the OCT/SLO and
      the MP-1.

PMID- 25774328
TI  - One-Year Feasibility Study of Replenish MicroPump for Intravitreal Drug Delivery:
      A Pilot Study.
AB  - PURPOSE: To determine the feasibility of the surgical procedure and to collect
      some safety data regarding the bioelectronics of a novel micro drug pump for
      intravitreal drug delivery in a Beagle dog model for up to 1 year. METHODS:
      Thirteen Beagle dogs were assigned to two groups. The experimental group (n = 11)
      underwent pars plana implantation of MicroPump; the body of which was sutured
      episclerally, while its catheter was secured at a pars plana sclerotomy. The
      control group (n = 2) underwent sham surgeries in the form of a temporary
      suturing of the MicroPump, including placement of the pars plana tube. Baseline
      and follow-up exams included ophthalmic examination and imaging. The experimental
      animals were euthanized and explanted at predetermined time points after surgery
      (1, 3, and 12 months), while the control animals were euthanized at 3 months. All
      operated eyes were submitted for histopathology. RESULTS: Eyes were scored
      according to a modified McDonald-Shadduck system and ophthalmic imaging. Neither
      the implanted eyes nor the control eyes showed clinically significant
      pathological changes beyond the expected surgical changes. The operated eyes
      showed neither significant inflammatory reaction nor tissue ingrowth through the
      sclerotomy site compared with the fellow eyes. CONCLUSION: This study shows that
      the Replenish Posterior MicroPump could be successfully implanted with good
      safety profile in this animal model. TRANSLATIONAL RELEVANCE: The results of this
      study in a Beagle dog model are supportive of the biocompatibility of Replenish
      MicroPump and pave the way to the use of these devices for ocular automated drug
      delivery after further testing in larger animal models.

PMID- 25774330
TI  - One-Year Outcomes of the SAVE Study: Sirolimus as a Therapeutic Approach for
      UVEitis.
AB  - PURPOSE: To determine the efficacy and safety of repeated intravitreal and
      subconjunctival administrations of sirolimus in patients with noninfectious
      uveitis at 1 year in the Sirolimus as a Therapeutic Approach UVEitis (SAVE)
      Study. METHODS: Open-label, prospective, and randomized interventional clinical
      trial in which 30 patients with noninfectious intermediate, posterior, or
      panuveitis were randomized 1:1 to receive sirolimus 352-MUg intravitreal or 1320
      MUg subconjunctival. Sirolimus was administered at days 0, 60, and 120. At month
      6, all subjects were allowed to receive sirolimus at intervals greater than or
      equal to 2 months and until month 12. Changes in vitreous haze (VH), visual
      acuity (VA), and retinal thickness at month 12 were compared with baseline.
      RESULTS: Of patients with active uveitis at baseline (n = 20), 70% showed greater
      than or equal to 2 steps reduction of VH at month 12 (P < 0.05), 88% (n = 7) of
      patients with inactive uveitis at baseline showed either no change or reduction
      of VH to no haze, 36% (n = 10) of all patients (n = 28) gained greater than or
      equal to one line of VA, 21% (n = 6) lost greater than or equal to 1 line, and
      43% (n = 12) showed no change. At the end of 1 year, no statistical differences
      in efficacy were found between intravitreal and subconjunctival groups. No
      serious adverse events were determined to be secondary to sirolimus. CONCLUSIONS:
      Repeated subconjunctival/intravitreal injections of sirolimus appear to be
      tolerated by patients with noninfectious uveitis over 12 months. Results from the
      index study suggest that sirolimus may provide benefits to patients with uveitis.
      Both intravitreal and subconjunctival routes demonstrate similar
      bioactivity/efficacy. The intravitreal route, however, was better tolerated.
      TRANSLATIONAL RELEVANCE: The SAVE Study illustrates for the first time the
      application of local formulations of sirolimus in non-infectious intermediate,
      posterior, and pan-uveitis. Subconjunctival/Intravitreal sirolimus may help to
      control inflammation while offering better tolerability/safety profiles than
      systemic therapies, including immunosuppressants and corticosteroids.

PMID- 25774331
TI  - Injectable Chemically Crosslinked Hydrogel for the Controlled Release of
      Bevacizumab in Vitreous: A 6-Month In Vivo Study.
AB  - PURPOSE: To evaluate the biocompatibility and 6-month in vivo release of
      bevacizumab from a hyaluronic acid/dextran-based in situ hydrogel after
      intravitreal injection in rabbit eye. METHODS: The in situ hydrogel was formed by
      the catalyst-free chemical crosslinking between vinylsulfone functionalized
      hyaluronic acid (HA-VS) and thiolated dextran (Dex-SH) at physiological
      condition. The pH 7.4 buffered mixture containing HA-VS, Dex-SH, and bevacizumab
      were injected into the vitreous of rabbit eyes by a 30-G needle. The
      biocompatibility was evaluated by intraocular pressure measurement, binocular
      indirect ophthalmoscope (BIO), full-field electroretinogram (ERG), and histology.
      The concentrations of both total and active bevacizumab in rabbit vitreous were
      determined by enzyme-linked immunosorbent assay. The concentration of bevacizumab
      in rabbit vitreous after bolus injection was simulated by one-compartment first
      order elimination model. RESULTS: A transparent gel was seen in the vitreous
      after injection. BIO images, ERG, and histology showed that the gel does not
      induce hemorrhage, retinal detachment, inflammation, or other gross pathological
      changes in rabbit eyes after injection. While the bolus intravitreal injected
      bevacizumab follows the first order elimination kinetics in rabbit eye, the in
      situ gel formation was able to prolong the retention of bevacizumab in rabbit eye
      at therapeutic relevant concentration for at least 6 months. The concentration of
      bevacizumab 6 months after injection was about 107 times higher than bolus
      injection. CONCLUSIONS: The new in situ hydrogel formulation of bevacizumab was
      biocompatible and able to prolong the retention of drug in rabbit eyes in vivo at
      therapeutic relevant concentration for at least 6 months. TRANSLATIONAL
      RELEVANCE: Although proven to be effective, monthly intravitreal injection of
      bevacizumab or other protein drugs may cause various complications. Extending the
      residence time of protein therapeutics in the eye can reduce the injection
      frequency, its associated complications, and treatment cost, which will be
      beneficial to both the patients and doctors. In this study, we showed that the in
      situ hydrogel-based controlled release system is a feasible option to tackle this
      problem.

PMID- 25774332
TI  - Suppression of Laser-Induced Choroidal Neovascularization by the Oral Medicine
      Targeting Histamine Receptor H4 in Mice.
AB  - PURPOSE: This study aimed to examine relationship of histamine receptor H4 (HRH4)
      and the pathogenesis of laser-induced choroidal neovascularization (laser-CNV)
      and to determine whether oral administration of HRH4 antagonists suppressed laser
      CNV in mice. METHODS: Laser photocoagulation was performed in mice to induce the
      laser-CNV. Histamine was administered intravitreously, and CNV volume was
      measured. Laser photocoagulation and intravitreous injection of HRH4 antagonist
      JNJ7777120 were performed after intraperitoneal injection of clodronate liposome,
      which depletes circulating monocyte-derived macrophages; CNV volume was compared
      with that in mice injected with control (dimethyl sulfoxide [DMSO]/PBS). Three
      days after laser-CNV, the F4/80+CD11b+ macrophage population in retinal pigment
      epithelium (RPE)/choroid complex was quantified with flow cytometry in wild-type
      and Hrh4-/- mice. The long-acting HRH4 antagonist JNJ28307474 was then
      administrated periorally, and the laser-CNV volume was compared with controls.
      RESULTS: Intravitreous injection of histamine did not affect laser-CNV volume.
      The laser-CNV from the eye injected with JNJ7777120 was equivalent to that
      injected with the DMSO/PBS in mice that had intraperitoneally received clodronate
      liposome. Flow cytometry after laser-CNV induction revealed a smaller
      F4/80+CD11b+ macrophage population in the RPE/choroid complex of Hrh4-/- mice
      than in wild-type mice. Oral administration of JNJ28307474 significantly reduced
      laser-CNV volume in wild-type mice. CONCLUSIONS: Our results suggested that HRH4
      positive macrophages played an important role in the pathogenesis of laser-CNV
      and that they require a different ligand from that of histamine. The oral
      administration of an HRH4 antagonist successfully reduced laser-CNV.
      TRANSLATIONAL RELEVANCE: Our results indicate that drugs targeting HRH4 are
      potentially a novel oral treatment for age-related macular degeneration.

PMID- 25774334
TI  - Merton's problem for an investor with a benchmark in a Barndorff-Nielsen and
      Shephard market.
AB  - To try to outperform an externally given benchmark with known weights is the most
      common equity mandate in the financial industry. For quantitative investors, this
      task is predominantly approached by optimizing their portfolios consecutively
      over short time horizons with one-period models. We seek in this paper to provide
      a theoretical justification to this practice when the underlying market is of
      Barndorff-Nielsen and Shephard type. This is done by verifying that an investor
      who seeks to maximize her expected terminal exponential utility of wealth in
      excess of her benchmark will in fact use an optimal portfolio equivalent to the
      one-period Markowitz mean-variance problem in continuum under the corresponding
      Black-Scholes market. Further, we can represent the solution to the optimization
      problem as in Feynman-Kac form. Hence, the problem, and its solution, is
      analogous to Merton's classical portfolio problem, with the main difference that
      Merton maximizes expected utility of terminal wealth, not wealth in excess of a
      benchmark. 

PMID- 25774335
TI  - Effects of human trampling on abundance and diversity of vascular plants,
      bryophytes and lichens in alpine heath vegetation, Northern Sweden.
AB  - This study investigated the effects of human trampling on cover, diversity and
      species richness in an alpine heath ecosystem in northern Sweden. We tested the
      hypothesis that proximity to trails decreases plant cover, diversity and species
      richness of the canopy and the understory. We found a significant decrease in
      plant cover with proximity to the trail for the understory, but not for the
      canopy level, and significant decreases in the abundance of deciduous shrubs in
      the canopy layer and lichens in the understory. Proximity also had a significant
      negative impact on species richness of lichens. However, there were no
      significant changes in species richness, diversity or evenness of distribution in
      the canopy or understory with proximity to the trail. While not significant,
      liverworts, acrocarpous and pleurocarpous bryophytes tended to have contrasting
      abundance patterns with differing proximity to the trail, indicating that
      trampling may cause shifts in dominance hierarchies of different groups of
      bryophytes. Due to the decrease in understory cover, the abundance of litter,
      rock and soil increased with proximity to the trail. These results demonstrate
      that low-frequency human trampling in alpine heaths over long periods can have
      major negative impacts on lichen abundance and species richness. To our
      knowledge, this is the first study to demonstrate that trampling can decrease
      species richness of lichens. It emphasises the importance of including species
      level data on non-vascular plants when conducting studies in alpine or tundra
      ecosystems, since they often make up the majority of species and play a
      significant role in ecosystem functioning and response in many of these extreme
      environments. 

PMID- 25774333
TI  - Coupling of P2Y receptors to G proteins and other signaling pathways.
AB  - P2Y receptors are G protein-coupled receptors (GPCRs) that are activated by
      adenine and uridine nucleotides and nucleotide sugars. There are eight subtypes
      of P2Y receptors (P2Y1, P2Y2, P2Y4, P2Y6, P2Y11, P2Y12, P2Y13, and P2Y14), which
      activate intracellular signaling cascades to regulate a variety of cellular
      processes, including proliferation, differentiation, phagocytosis, secretion,
      nociception, cell adhesion, and cell migration. These signaling cascades operate
      mainly by the sequential activation or deactivation of heterotrimeric and
      monomeric G proteins, phospholipases, adenylyl and guanylyl cyclases, protein
      kinases, and phosphodiesterases. In addition, there are numerous ion channels,
      cell adhesion molecules, and receptor tyrosine kinases that are modulated by P2Y
      receptors and operate to transmit an extracellular signal to an intracellular
      response.

PMID- 25774336
TI  - Immunohistochemical analysis in ethinylestradiol-treated breast cancers after
      prior long-term estrogen-deprivation therapy.
AB  - BACKGROUND: Estrogen receptor (ER) positive breast cancer can often be treated by
      hormone therapy; however a certain population of ER-positive patients become
      resistant to hormone therapy after long-term hormone treatment. Ethinylestradiol
      (EE2) is a derivative of estrogen, which has shown promising effects in these
      patients. METHODS: We successfully obtained tissue samples from 6 patients
      undergoing EE2 treatment and examined 13 well-known breast cancer-related factors
      by immunohistochemistry. Of the 6 patients, 5 responded but one patient did not.
      RESULTS: Before EE2 treatment, staining for both ER and androgen receptor (AR)
      was strong in the nucleus, and the progesterone receptor (PgR) was almost no
      staining. EE2 treatment significantly down-regulated ER and up-regulated PgR
      while nuclear and cytosolic AR were oppositely down- and up-regulated,
      respectively. Cytosolic staining of BRCA1 was significantly up-regulated by EE2
      whereas nuclear staining tended to decrease. Individual comparisons suggested
      less induction of PgR and decreasing AKT but increasing pAKT in the non-responder
      following EE2 treatment. CONCLUSIONS: Our observations revealed that EE2
      activated ER downstream genes; however it did not stimulate cell growth. This
      suggests that hormone resistant cells might receive growth signals from a non
      genomic pathway and this may be reflected in their sensitivity to EE2 treatment.

PMID- 25774337
TI  - Looking through the patient lens - Improving best practice for young people with
      juvenile idiopathic arthritis transitioning into adult care.
AB  - We describe a qualitative study to establish the emerging needs of young people
      with juvenile idiopathic arthritis (JIA) as they go through the transition
      process, identifying which elements are valued and where support gaps exist.
      Qualitative interviews with healthcare professionals, young people with JIA and
      their parents explored the lived experience of transition to care in an adult
      rheumatology clinic. Perspectives of the experience and reflections of the
      process of transitioning were captured along with the young people's views of
      optimal support. Service provision in the clinical environment varied. Service
      design for this particular patient group has an impact on how young people
      optimise management of, and engagement with, their condition during young
      adulthood. Two specific themes emerged that had the greatest impact on defining a
      positive user experience of transitioning care: tailored service provision within
      the clinical environment and support for those living with JIA beyond the clinic
      doors (we have termed these the lived experience). Factors of importance to young
      people with JIA were grouped into key domains, namely: day-to-day life with JIA,
      emotional and developmental factors and a desire for independence. The young
      people and healthcare professionals interviewed in this small qualitative study
      highlighted some common themes considered critical in the development and
      organisation of an excellent care pathway from paediatric to adult healthcare.
      Aligning the clinical process with young people's individual needs and lifestyle
      creates stronger beginnings in adult care. 

PMID- 25774338
TI  - The Epigenetic Impact of Cruciferous Vegetables on Cancer Prevention.
AB  - The answer to chemoprevention has perhaps been available to the general public
      since the dawn of time. The epigenetic diet is of extreme interest, for research
      suggests that cruciferous vegetables are not only an important source of
      nutrients, but perhaps a key to eliminating cancer as life threatening disease.
      Cruciferous vegetables such as kale, cabbage, Brussels sprouts, and broccoli
      sprouts contain chemical components, such as sulforaphane (SFN) and indole-3
      carbinol (I3C), which have been revealed to be regulators of microRNAs (miRNAs)
      and inhibitors of histone deacetylases (HDACs) and DNA methyltransferases
      (DNMTs). The mis-regulation and overexpression of these genes are responsible for
      the uncontrolled cellular proliferation and viability of various types of cancer
      cells. The field of epigenetics and its incorporation into modern medicinal
      investigation is an exponentially growing field of interest and it is becoming
      increasingly apparent that the incorporation of an epigenetic diet may in fact be
      the key to chemoprevention.

PMID- 25774340
TI  - Anal duplication in a one-year-old girl.
AB  - We report a case of a patient with anal duplication discovered incidentally at 1
      year of age. Pre-operative evaluation excluded any complications or associated
      anomalies. She underwent surgical excision with an excellent outcome.

PMID- 25774339
TI  - MicroRNA Regulating Glutathione S-Transferase P1 in Prostate Cancer.
AB  - Glutathione S-transferase P1 (GSTP1), an enzyme involved in detoxification
      process, is frequently inactivated in prostate cancer due to epigenetic
      modifications. Through in silico analysis we identified a subset of miRNAs that
      are putative targets in regulating GSTP1. miRNAs are small endogenous non-coding
      RNA that are critical regulators of various physiologic and pathologic processes
      and their level of expression may play a precise role in early diagnosis and
      prognosis of cancer. These small molecules have been detected in a wide variety
      of human biological specimens including blood, serum, urine, ejaculate and
      tissues, which could be utilized as clinically useful biomarker in early
      detection and prognosis of prostate cancer. The chapter summarizes the current
      knowledge about miRNA involved in GSTP1 regulation in prostate cancer and their
      potential as useful biomarkers of disease for early detection and prognosis,
      along with challenges and limitations in this development.

PMID- 25774341
TI  - Comparison of changes over time in leukocyte counts in Yucatan minipigs
      irradiated with simulated solar particle event-like radiation.
AB  - During a major solar particle event (SPE), astronauts in space are at risk of
      exposure to an increased dose of proton radiation. The whole body distribution of
      the absorbed SPE proton dose is inhomogeneous, and such an inhomogeneous SPE
      proton dose can be simulated by electron radiation. Using Yucatan minipigs as an
      animal model, we compared the time courses of leukocyte count changes after
      exposure to proton simulated SPE (pSPE) radiation or electron simulated SPE
      (eSPE) radiation. The results demonstrated that the time required after
      irradiation to reach the lowest leukocyte counts was generally comparable between
      the pSPE and eSPE radiation exposures. However, the leukocyte count often
      recovered faster after electron irradiation compared to proton irradiation at the
      corresponding doses. In addition, the radiation dose required to achieve
      comparable magnitudes of leukocyte count decrease was higher in the eSPE animals
      than for the pSPE animals. In conclusion, based on the magnitude of the decrease
      and the time required to reach the lowest leukocyte counts after irradiation, the
      pSPE radiation was more effective than the eSPE radiation in reducing the
      peripheral leukocyte counts. Lymphocytes appeared to be the most sensitive type
      of leukocytes in response to either type of SPE radiation. It is particularly
      noteworthy that following exposure to pSPE radiation at the skin doses >5 Gy, the
      neutrophils do not recover from the radiation damage at times up to 30 days, and
      the neutrophils have not recovered to their baseline levels even at 90 days post
      irradiation. These results suggest a marked difference in the ability of the
      neutrophils to recover from pSPE radiation compared with the results observed for
      eSPE radiation.

PMID- 25774342
TI  - Motivational Interviewing Support for a Behavioral Health Internet Intervention
      for Drivers with Type 1 Diabetes.
AB  - While Internet interventions can improve health behaviors, their impact is
      limited by program adherence. Supporting program adherence through telephone
      counseling may be useful, but there have been few direct tests of the impact of
      support. We describe a Telephone Motivational Interviewing (MI) intervention
      targeting adherence to an Internet intervention for drivers with Type 1 Diabetes,
      DD.com, and compare completion of intervention benchmarks by those randomized to
      DD.com plus MI vs. DD.com only. The goal of the pre-intervention MI session was
      to increase the participant's motivation to complete the Internet intervention
      and all its assignments, while the goal of the post-treatment MI session was to
      plan for maintaining changes made during the intervention. Sessions were semi
      structured and partially scripted to maximize consistency. MI Fidelity was coded
      using a standard coding system, the MITI. We examined the effects of MI support
      vs. no support on number of days from enrollment to program benchmarks. Results
      show that MI sessions were provided with good fidelity. Users who received MI
      support completed some program benchmarks such as Core 4 (t176 df= -2.25; p<.03)
      and 11 of 12 monthly driving diaries significantly sooner, but support did not
      significantly affect time to intervention completion (t177 df= -1.69; p<. 10) or
      rates of completion. These data suggest that there is little benefit to therapist
      guidance for Internet interventions including automated email prompts and other
      automated minimal supports, but that a booster MI session may enhance collection
      of follow-up data.

PMID- 25774343
TI  - Carotid intima-media thickness (CIMT) and carotid plaques in young Nepalese
      patients with angiographically documented coronary artery disease.
AB  - BACKGROUND: Carotid intima-media thickness (CIMT) and carotid plaques are non
      invasive surrogate markers of early evaluation of coronary artery disease (CAD)
      and sub clinical atherosclerosis. The objective of the study was to evaluate CIMT
      and carotid plaques in less than 45 years old Nepalese patients with
      angiographically proven CAD. METHODS: A total of 54 patients with
      angiographically documented CAD at less than 45 years of age were enrolled. CAD
      was confirmed by coronary angiography. Demographic profile was obtained. High
      resolution B-mode ultrasound was used to detect the CIMT and carotid plaques.
      RESULTS: The study population included 44 males and 10 females, with a mean +/-
      SD age of 38.4+/-4.3 years (range, 25-44 years). Cardiovascular risks factors
      included smoking in 81%, Hypertension in 52%, diabetes in 19% and alcohol
      consumption in 78% of patients. Lipid profile (mean +/- SD) was normal except for
      elevated triglyceride (TG) levels of 204+/-130.8 mg/dL. By angiography, 64.8% had
      single vessel disease, 26% had double vessel disease and 9.2% had triple vessel
      disease. Ultrasound detected either thickened CIMT or presence of plaques in 46
      (85.2%) cases (group-A) and 8 (14.8%) had negative (normal) carotid study (group
      B). Among the 46 patients with positive findings 63% had carotid plaques and 37%
      had thickened CIMT only. The majority (69%) of the carotid plaques were detected
      at the carotid bulbs. In total population, carotid plaque was detected in 53.7%
      of cases. There was no statistical significant difference of age, body mass index
      (BMI) and lipid level between group-A and group-B. CONCLUSIONS: Increased CIMT
      and carotid plaques are detected in majority of the young Nepalese patients with
      angiographically documented CAD. The majority of carotid plaques are detected at
      the carotid bulbs. Routine carotid ultrasound study in young individuals with CAD
      risk factors appears worthwhile.

PMID- 25774344
TI  - Impact of statins and beta-blocker therapy on mortality after coronary artery
      bypass graft surgery.
AB  - BACKGROUND: We conducted a retrospective cohort study of patients after first
      time isolated coronary artery bypass graft surgery (CABG) and assessed the impact
      of a discharge regimen including beta-blockers and statin therapy and their
      relationship to long-term all cause mortality and major adverse cardiovascular
      events (MACE). METHODS: We identified patients age >18 years, undergoing first
      time isolated CABG from 1993 to 2005. Patients were identified using the
      Cardiovascular Information Registry (CVIR). We collected follow-up information at
      30, 60, 90 days and yearly follow-up. The registry is approved for use in
      research by the institutional review broad. RESULTS: We identified 5,205 patients
      who underwent single isolated CABG between January 1993 and December 2005. The
      mean age was 64.5+/-9.7 years and over 70% were male. There was a significant
      difference in the low density lipoproteins (LDL) concentration between those with
      or without statin medications (134+/-41.9 mg/dL) (no statin) vs. 126+/-44.8 mg/dL
      (with statin), P=0.001. A discharge regimen with statin therapy was associated
      with and overall reduction in 30 day, 1 year and long-term mortality. In
      addition, overall the triple ischemic endpoint of death, myocardial infarction
      (MI) and stroke was also significantly lower in the statin vs. no-statin group.
      In addition, statin and beta-blockers exerted synergistic effect on overall
      mortality outcomes short-term and in the long-term. We note that the predictors
      of overall death include no therapy with statin therapy and age [hazard ratios
      (HR) 1.1, 95% CI: 1.04-1.078, P<0.001] and presence of renal failure (HR 2.0,
      P=0.005). The estimated 11-year Kaplan Meier curves for mortality between the two
      groups starts to diverge immediately post discharge after single isolated CABG
      and continue to diverge through out the follow-up period. CONCLUSIONS: A post
      discharge regimen of statins independently reduces overall and 1 year mortality.
      These results confirm those of earlier studies within a contemporary surgical
      population and support the current clinical guidelines.

PMID- 25774345
TI  - microRNA-based diagnostics and therapy in cardiovascular disease-Summing up the
      facts.
AB  - Circulating microRNAs (miRNAs) are discussed as potential disease-specific
      biomarkers in cardiovascular disease. Their diagnostic value has been examined in
      numerous studies and animal models with respect to coronary artery disease (CAD)
      and myocardial infarction (MI) and the prognostic abilities of circulating miRNAs
      in risk stratification of future disease have been evaluated. Various miRNAs are
      described to complement protein-based biomarkers or classical risk factors in the
      diagnosis of CAD or MI and even represent potential new biomarkers in the
      discrimination of unstable angina pectoris (UAP). Signatures consisting of sets
      of multiple miRNAs seem to improve the predictive power compared to single
      miRNAs. Furthermore, the emerging field of miRNA-based therapeutics has reached
      cardiovascular research. The first promising in vitro results are raising hope
      for future clinical application. However, methods and material used for RNA
      isolation, miRNA detection and normalization steps still lack ways of
      standardization and need to be considered carefully. This article reviews the
      current knowledge of miRNAs in cardiovascular disease focusing on CAD and MI and
      will provide an overview regarding the use of circulating miRNAs as biomarkers
      and potential therapeutic targets in the field of CAD. 

PMID- 25774346
TI  - Spontaneous coronary artery dissection-A review.
AB  - Spontaneous coronary artery dissection (SCAD) is an infrequent and often missed
      diagnosis among patients presenting with acute coronary syndrome (ACS).
      Unfortunately, SCAD can result in significant morbidities such as myocardial
      ischemia and infarction, ventricular arrhythmias and sudden cardiac death. Lack
      of angiographic recognition from clinicians is a major factor of under-diagnosis.
      With the advent of new imaging modalities, particularly with intracoronary
      imaging, there has been improved diagnosis of SCAD. The aim of this paper is to
      review the epidemiology, etiology, presentation, diagnosis and management of
      SCAD. 

PMID- 25774347
TI  - Percutaneous left atrial appendage closure-An alternative strategy for
      anticoagulation in atrial fibrillation and hereditary hemorrhagic telangiectasia?
AB  - Many patients with hereditary hemorrhagic telangiectasia (HHT) are unable to
      sustain oral anticoagulation (OAC) because of severe epistaxis, gastrointestinal
      (GI) bleeding and the risk of life-threatening bleeding from cerebral
      arteriovenous malformations (CAVMs) or pulmonary arteriovenous malformations
      (PAVMs). In patients with atrial fibrillation (AF), most thromboembolic
      complications arise from the left atrial appendage (LAA) and percutaneous
      transcatheter LAA closure proved to be non-inferior to OAC at mid-term follow-up.
      We report our experience with LAA closure in HHT with a follow-up of 12 months.
      Percutaneous LAA closure was performed in five patients with both HHT and high
      thromboembolic risk AF (CHA2DS2-VASc score >=2) without peri-procedural
      complications. At 3 months no thromboembolic event occurred. After 12 months one
      patient had a transient ischemic attack while another patient had recurrence of
      stroke, this latter patient had a significant stenosis of the carotid artery and
      an incomplete closure of the LAA without any signs of thrombus on echocardiogram.
      Both patients had a non-treatable pulmonary right-to-left shunt (RLS).
      Percutaneous closure of the LAA may provide an alternative strategy to long-term
      OAC therapy in HHT patients with AF induced high stroke risk and intolerance for
      OAC. 

PMID- 25774348
TI  - Intravascular imaging in Kounis syndrome: role of IVUS and OCT in achieving an
      etiopathogenic diagnosis.
AB  - We report a case of a 60-year-old male patient presenting with anaphylactic
      response to anchovies associated with an acute coronary syndrome. His history was
      remarkable for coronary artery disease treated with a drug eluting stent to the
      right coronary artery six years before and stent fracture documented by coronary
      angiography four years prior to the event. Coronary angiography on admission
      revealed a very late stent thrombosis (VLST) in the right coronary artery.
      Intracoronary imaging techniques (IVUS and OCT) were used and were key to discard
      main causes of VLST. We described the characteristics of intracoronary images,
      along with the advantages and disadvantages of these techniques. The findings
      described in this case could explain a new physiopathological mechanism of stent
      thrombosis occurring in stent fractures. 

PMID- 25774349
TI  - Evidence for myocardial CT perfusion imaging in the diagnosis of hemodynamically
      significant coronary artery disease.
AB  - This editorial discusses a recent paper published in the August issue of
      Radiology about the diagnostic value of myocardial computer tomography (CT)
      perfusion imaging in the detection of hemodynamically significant coronary
      stenosis when compared to single-photon emission CT (SPECT) imaging based on a
      secondary analysis of CORE320 study. Three aspects including high diagnostic
      sensitivity of CT perfusion imaging, moderate specificity of SPECT imaging and
      lack of use of attenuation correction in SPECT imaging have been discussed with
      reference to the current literature, and some suggestions have been highlighted
      for future studies to improve the diagnostic performance of CT perfusion and
      SPECT imaging in the diagnostic evaluation of coronary artery disease. 

PMID- 25774350
TI  - Myocardial CT perfusion for the prediction of obstructive coronary artery
      disease, valuable or not?
AB  - Adenosine stress myocardial computed tomography perfusion (CTP) is a relatively
      new myocardial perfusion imaging technique. Together with coronary CT angiography
      (CTA) it provides anatomic and functional information of coronary artery disease
      (CAD). In previous studies, the combination of these techniques demonstrated to
      be valuable for identifying hemodynamically significant stenoses. George et al.,
      performed a secondary analysis on the CORE320 study and compared the diagnostic
      performance of CTP to single positron emission computed tomography (SPECT)
      myocardial perfusion imaging (MPI) to diagnose obstructive CAD (defined as >=50%
      luminal stenosis). In this editorial the results and limitations of the study are
      discussed, as well as opportunities that this new perfusion technique brings with
      it. 

PMID- 25774351
TI  - Association of coronary plaque burden with fractional flow reserve: should we
      keep attempting to derive physiology from anatomy?
AB  - Coronary computed tomography angiography (CTA) has been used increasingly for the
      diagnosis of coronary artery disease over the past decade. Compared to invasive
      coronary angiography (ICA), coronary CTA has the ability to visualize and
      quantify atherosclerotic plaque both calcified and non-calcified. Traditional
      measures of evaluating a coronary stenosis such as diameter stenosis, area
      stenosis, minimal lumen diameter and minimal luminal area are limited in their
      ability to predict its functional significance especially when diameter stenosis
      ranges between 30-69% (intermediate range). Measurement of invasive fractional
      flow reserve (FFR) is considered the gold standard for assessment of the
      hemodynamic significance of a stenosis. The current study by Nakazato et al.
      evaluates the performance of an emerging coronary CTA-derived anatomical measure
      "percent aggregate plaque volume" to improve the detection of hemodynamic
      significant stenosis as compared with invasive FFR. 

PMID- 25774352
TI  - Computed tomography quantification of coronary plaque volume may provide further
      perspective on intermediate severity stenoses.
AB  - Coronary computed tomography angiography (CCTA) is an emerging modality for
      comprehensive non-invasive assessment of coronary artery disease (CAD). CCTA was
      traditionally used for anatomical assessment of coronary plaque, including
      luminal narrowing, plaque burden, location, and composition. Preliminary studies
      have also demonstrated CCTA's capabilities for functional assessment of coronary
      plaque, including fractional flow reserve (FFR) and myocardial perfusion-albeit
      they are not routinely available at all centers and are focus of research.
      Although the identification and development of treatment strategies of severely
      stenotic lesions has advanced tremendously over the past years, the evaluation,
      prognostication, and treatment of patients with intermediate severity stenosis in
      whom there is equipoise between invasive versus medical management is only now
      receiving attention. Intermediate severity stenosis is the most likely to benefit
      from additional measures of disease beyond traditional clinical risk profiling
      and CCTA visual examination. Nakazato et al. studied 58 patients with
      intermediate severity stenosis and quantified the percent aggregate plaque volume
      (%APV), a novel measure of total arterial plaque disease. %APV had the highest
      correlation with ischemic lesions on FFR, outperforming luminal diameter, luminal
      area, minimal lumen diameter, and minimal lumen area. This study extracts
      additional information from pre-existing CT data-sets and suggest novel concept
      that might improve classification of moderate severity coronary stenoses. 

PMID- 25774353
TI  - Telerehabilitation for patients with heart failure.
AB  - Heart failure is a chronic and progressive condition that is associated with high
      morbidity and mortality rates. Even though cardiac rehabilitation (CR) has been
      shown to be beneficial to heart failure patients, only a very small proportion of
      them will actually be referred and eventually participate. The low participation
      rate is due in part to accessibility and travel difficulties. Telerehabilitation
      is a new approach in the rehabilitation field that allows patients to receive a
      complete rehabilitation program at home in a safe manner and under adequate
      supervision. We believe that by increasing accessibility to CR,
      telerehabilitation programs will significantly improve heart failure patients'
      functional capacity and quality of life. However, it is crucial to provide policy
      makers with evidence-based data on cardiac telerehabilitation if we want to see
      its successful implementation in heart failure patients. 

PMID- 25774354
TI  - Beam hardening artifact reduction using dual energy computed tomography:
      implications for myocardial perfusion studies.
AB  - BACKGROUND: Myocardial computed tomography perfusion (CTP) using conventional
      single energy (SE) imaging is influenced by the presence of beam hardening
      artifacts (BHA), occasionally resembling perfusion defects and commonly observed
      at the left ventricular posterobasal wall (PB). We therefore sought to explore
      the ability of dual energy (DE) CTP to attenuate the presence of BHA. METHODS:
      Consecutive patients without history of coronary artery disease who were referred
      for computed tomography coronary angiography (CTCA) due to atypical chest pain
      and a normal stress-rest SPECT and had absence or mild coronary atherosclerosis
      constituted the study population. The study group was acquired using DE and the
      control group using SE imaging. RESULTS: Demographical characteristics were
      similar between groups, as well as the heart rate and the effective radiation
      dose. Myocardial signal density (SD) levels were evaluated in 280 basal segments
      among the DE group (140 PB segments for each energy level from 40 to 100 keV; and
      140 reference segments), and in 40 basal segments (at the same locations) among
      the SE group. Among the DE group, myocardial SD levels and myocardial SD ratio
      evaluated at the reference segment were higher at low energy levels, with
      significantly lower SD levels at increasing energy levels. Myocardial signal-to
      noise ratio was not significantly influenced by the energy level applied,
      although 70 keV was identified as the energy level with the best overall signal
      to-noise ratio. Significant differences were identified between the PB segment
      and the reference segment among the lower energy levels, whereas at >=70 keV
      myocardial SD levels were similar. Compared to DE reconstructions at the best
      energy level (70 keV), SE acquisitions showed no significant differences overall
      regarding myocardial SD levels among the reference segments. CONCLUSIONS: BHA
      that influence the assessment of myocardial perfusion can be attenuated using DE
      at 70 keV or higher.

PMID- 25774355
TI  - Child tears.

PMID- 25774356
TI  - Beyond Mutations: Additional Mechanisms and Implications of SWI/SNF Complex
      Inactivation.
AB  - SWI/SNF is a major regulator of gene expression. Its role is to facilitate the
      shifting and exposure of DNA segments within the promoter and other key domains
      to transcription factors and other essential cellular proteins. This complex
      interacts with a wide range of proteins and does not function within a single,
      specific pathway; thus, it is involved in a multitude of cellular processes,
      including DNA repair, differentiation, development, cell adhesion, and growth
      control. Given SWI/SNF's prominent role in these processes, many of which are
      important for blocking cancer development, it is not surprising that the SWI/SNF
      complex is targeted during cancer initiation and progression both by mutations
      and by non-mutational mechanisms. Currently, the understanding of the types of
      alterations, their frequency, and their impact on the SWI/SNF subunits is an area
      of intense research that has been bolstered by a recent cadre of NextGen
      sequencing studies. These studies have revealed mutations in SWI/SNF subunits,
      indicating that this complex is thus important for cancer development. The
      purpose of this review is to put into perspective the role of mutations versus
      other mechanisms in the silencing of SWI/SNF subunits, in particular, BRG1 and
      BRM. In addition, this review explores the recent development of synthetic
      lethality and how it applies to this complex, as well as how BRM polymorphisms
      are becoming recognized as potential clinical biomarkers for cancer risk.
      SIGNIFICANCE: Recent reviews have detailed the occurrence of mutations in nearly
      all SWI/SNF subunits, which indicates that this complex is an important target
      for cancer. However, when the frequency of mutations in a given tumor type is
      compared to the frequency of subunit loss, it becomes clear that other non
      mutational mechanisms must play a role in the inactivation of SWI/SNF subunits.
      Such data indicate that epigenetic mechanisms that are known to regulate BRM may
      also be involved in the loss of expression of other SWI/SNF subunits. This is
      important since epigenetically silenced genes are inducible, and thus, the
      reversal of the silencing of these non-mutationally suppressed subunits may be a
      viable mode of targeted therapy.

PMID- 25774357
TI  - Alterations of host cell ubiquitination machinery by pathogenic bacteria.
AB  - Response of immune and non-immune cells to pathogens infections is a very dynamic
      process. It involves the activation/modulation of many pathways leading to actin
      remodeling, membrane engulfing, phagocytosis, vesicle trafficking, phagolysosome
      formation, aiming at the destruction of the intruder. These sophisticated and
      rapid mechanisms rely on post-translational modifications (PTMs) of key host
      cells' factors, and bacteria have developed various strategies to manipulate them
      to favor their survival. Among these important PTMs, ubiquitination has emerged
      as a major mediator/modulator/regulator of host cells response to infections that
      pathogens have also learned to use for their own benefit. In this mini-review, we
      summarize our current knowledge about the normal functions of ubiquitination
      during host cell infection, and we detail its hijacking by model pathogens to
      escape clearance and to proliferate. 

PMID- 25774358
TI  - Pathogenesis, management and prevention of atypical femoral fractures.
AB  - Much attention has been paid to the relationship between atypical femoral
      fractures (AFF) and use of bisphosphonates (BPs). While a significant cause
      effect relationship was not established in earlier studies, more recent data
      shows a growing relationship between AFF and BPs use. The definition of an 'AFF'
      has also undergone significant changes. This review briefly summarizes the
      definition, pathogenesis, and management of AFF. 

PMID- 25774359
TI  - Relationship between Decrease in Serum Sodium Level and Bone Mineral Density in
      Osteoporotic Fracture Patients.
AB  - BACKGROUND: Recently, it has been suggested that decrease in serum sodium level
      is associated with osteoporosis. However, no study in Korea has reported the
      association of decrease in serum sodium level with osteoporosis. In this study,
      we investigated the relationship between the decrease in serum sodium level and
      severity of osteoporotic fracture in patients. METHODS: We enrolled 290 subjects
      who were admitted and operated at Soonchunhyang University Hospital due to major
      fractures. For the control group, we enrolled 1,027 subjects who visited a health
      promotion center. We carried a 1:1 matching with age and sex from the case group.
      RESULTS: In a total of 164 age- and sex-matched subjects, serum sodium level was
      significantly lower in the fracture group than in the non-fracture group
      (P=0.001). Serum sodium level was significantly lower in the severe osteoporosis
      group than that in the non-severe osteoporosis group (P=0.002). Old age and
      decrease in serum sodium level were independent risk factors of osteoporosis
      (odds ratio [OR]=1.088, P=0.008, confidence interval [CI]=[1.022-1.157]; OR=
      0.840, P=0.037, CI=0.713-0.989). CONCLUSIONS: Serum sodium level was
      significantly lower in the fracture group than that in the non-fracture group and
      in the severe osteoporosis group than that in the non-severe osteoporosis group.
      Based on our results, the decrease in serum sodium level could be an independent
      risk factor for osteoporosis.

PMID- 25774360
TI  - Incidence and mortality after proximal humerus fractures over 50 years of age in
      South Korea: national claim data from 2008 to 2012.
AB  - BACKGROUND: There has been lack of epidemiology of proximal humerus fracture
      using nationwide database in Asia. The purpose of this study was to investigate
      the incidence of proximal humerus fracture and its mortality following proximal
      humerus fracture in Korean over 50 years of age. METHODS: The Korean National
      Health Insurance data were evaluated to determine the incidence and mortality of
      proximal humerus fracture aged 50 years or older from 2008 through 2012. RESULTS:
      Proximal humerus fracture increased by 40.5% over 5 year of study. The incidence
      of fracture increased from 104.7/100,000 in 2008 to 124.7/100,000 in 2012 in
      women and from 45.3/100,000 in 2008 to 52.0/100,000 in 2012 in men, respectively.
      One year mortality rate after proximal humerus fracture was 8.0% in 2008 and 7.0%
      in 2012. One year mortality rate were 10.8% for men and 7.0% for women in 2008
      and 8.5% for men and 6.4% for women in 2012. CONCLUSIONS: Our study showed that
      the proximal humerus fracture in elderly was recently increasing and associated
      with high mortality in Korea. Considering proximal humerus fracture was
      associated with an increased risk of associated fractures and an increased
      mortality risk, public health strategy to prevent the proximal humerus fracture
      in elderly will be mandatory.

PMID- 25774361
TI  - The demographic changes of menopausal and geripausal women in Korea.
AB  - BACKGROUND: Osteoporosis and resultant fracture seems to be the most common
      skeletal disease, affecting female exclusively. Osteoporosis increases
      exponentially with menopause and age. Therefore the demographic data seems to be
      the most important & fundamental for the study of osteoporosis epidemiology.
      METHODS: This study was to analyzed population projection from 1960 to 2060. We
      evaluated the demographic change of female, postmenopausal and elderly geripausal
      population in South Korea using Korean statistical information service database
      as basic fundamental data for osteoporosis epidemiology. RESULTS: According to
      population projection, the total female population will be exceeds the total male
      population since 2015 and maximize up to 2030. In 2030, nearly half of female
      will become postmenopausal and one fourth of women elderly will be geripausal. Of
      total female population in 2060, the proportion of postmenopausal women will be
      increased up to 59.8%. CONCLUSIONS: According to population projection in South
      Korea, six of ten women in 2060 will be postmenopausal and seven of ten
      postmenopausal women geripausal. As expected to increase proportion of elderly
      women, dramatic rise of osteoporosis and osteoporotic fracture also expected.
      Health providers pay more attention to postmenopausal and geripausal women health
      care.

PMID- 25774362
TI  - Risk of hip fractures in men with alpha-blockers: a nationwide study base on
      claim registry.
AB  - BACKGROUND: Alpha-blocker can result in falling and fractures because of adverse
      effect such as orthostatic hypotension due to vasodilatory effect. We
      investigated the association between the alpha-blocker and the risk of
      osteoporotic hip fractures using a nationwide claim database. METHODS: We
      identified 1,051,651 men 65 years of age or older who had prescription records of
      alpha-blocker from nationwide medical claim database, from 2007 to 2012. Alpha
      blockers were classified as non-specific general (NSG), non-specific slow-release
      (NSSR), uro-specific general (USG), and uro-specific slow release (USSR).
      RESULTS: Total of 6,553 hip fractures were observed. The incidences of hip
      fracture within 1 year were higher than those of the reference periods in all
      type of alpha-blocker. Hazard ratio peaked at early period of alpha-blocker, and
      decreased with time, regardless of type of alpha-blocker. CONCLUSIONS: Use of
      alpha-blocker is associated with increased risk of hip fracture, especially in
      early use.

PMID- 25774363
TI  - Fracture in a Young Male Patient Leading to the Diagnosis of Wilson's Disease: A
      Case Report.
AB  - Wilson's disease is a rare genetic disorder that has abnormal copper metabolism.
      Although the disease's main problems are found in liver and brain, some studies
      revealed manifestation of various musculoskeletal problems in the patients. In
      this report, we encountered a young patient who had fracture in the forearm bone.
      Initially, exception to a previous history of fracture from a motorcycle
      accident, the patient did not have any medical or drug use history, and
      laboratory work-ups were insignificant. However, with suspicion on his bone's
      integrity, bone densitometry was recommended and revealed osteopenic change. To
      disclose a cause for the change, questions were made to recall any particular
      history or event, and his complaint of recent vision loss led to ophthalmologic
      consultation where under slit-lamp test found Kayser-Fleischer ring. Further
      laboratory work-up found low levels of serum copper and ceruloplasmin and high
      copper level in 24-hr urine sample that led to the diagnosis of Wilson's disease.
      Although Wilson's disease has been frequently noticed with considerable
      musculoskeletal manifestation, it rarity makes the diagnosis illusive to a
      physician. Hence, despite of its rarity, it is imperative to remember the
      disease's bony manifestation, and it should be suspected in young patients with
      demineralized bone when the reason for brittle bone cannot be answered with other
      better known conditions. 

PMID- 25774364
TI  - A case of low bone mineral density with vitamin d deficiency due to prolonged
      lactation and severe malnutrition.
AB  - Malnutrition associated vitamin D deficiency contributes to the calcium loss from
      bone and results in osteoporosis and osteomalacia at final stage. Osteomalacia is
      characterized with softening of bone secondary to defective bone mineralization.
      Here, we report a case of possible osteomalacia caused by prolonged lactation and
      severe malnutrition in 35-year-old female. She was a housewife and her body mass
      index was 11.8 kg/m(2). She was diagnosed with severe osteoporosis in regular
      health check-up 2 years ago, but did not take any medication. Nine months ago,
      she had been treated with anti-tuberculosis medications for 6 month due to active
      pulmonary tuberculosis. After complete remission of pulmonary tuberculosis, she
      had lost her appetite severely. Furthermore, she felt gait difficulty and
      suffered from generalized bone pain. On serologic examination, hypocalcemia,
      hypophosphatemia, high alkaline phosphatase, low vitamin D3 and high parathyroid
      hormone level were seen. In the bone mineral density, Z-score from her lumbar
      spine was -6.5. She was treated with oral calcium and vitamin D3 intramuscularly.
      After 1 year treatment, she felt significant improvement in bone pain and could
      walk alone. Also her serum calcium, phosphate and vitamin D3 level are all
      normalized. 

PMID- 25774365
TI  - "Functionally" univentricular hearts: impact of pre-natal diagnosis.
AB  - Within the last few decades the pre-natal echocardiographic diagnosis of
      congenital heart defects has made substantial progresses, particularly for the
      identification of complex malformation. "Functionally" univentricular hearts
      categorize a huge variety of heart malformations. Since no one of the patients
      with these congenital heart defects can ever undergo a bi-ventricular type of
      repair, early recognition and decision-making from the neonatal period are
      required in order to allow for appropriate multiple-step diagnostic and treatment
      procedures, either of interventional cardiology and/or surgery, on the pathway of
      "univentricular" heart. In the literature strong disagreements exist about the
      potential impact of the pre-natal diagnosis on the early and late outcomes of
      complex congenital heart defects. This review of the recent reports has been
      undertaken to better understand the impact of pre-natal diagnosis in
      "functionally" univentricular hearts taking into consideration the following
      topics: pre-natal screening, outcomes and survival, general morbidity, neurologic
      and developmental consequences, pregnancy management and delivery planning,
      resources utilization and costs/benefits issues, ethical implications, parents
      counseling, and interruption of pregnancy versus treatment. 

PMID- 25774366
TI  - Compound-specific isotope analysis of diesel fuels in a forensic investigation.
AB  - Compound-specific isotope analysis (CSIA) offers great potential as a tool to
      provide chemical evidence in a forensic investigation. Many attempts to trace
      environmental oil spills were successful where isotopic values were particularly
      distinct. However, difficulties arise when a large data set is analyzed and the
      isotopic differences between samples are subtle. In the present study,
      discrimination of diesel oils involved in a diesel theft case was carried out to
      infer the relatedness of the samples to potential source samples. This
      discriminatory analysis used a suite of hydrocarbon diagnostic indices, alkanes,
      to generate carbon and hydrogen isotopic data of the compositions of the
      compounds which were then processed using multivariate statistical analyses to
      infer the relatedness of the data set. The results from this analysis were put
      into context by comparing the data with the delta(13)C and delta(2)H of alkanes
      in commercial diesel samples obtained from various locations in the South Island
      of New Zealand. Based on the isotopic character of the alkanes, it is suggested
      that diesel fuels involved in the diesel theft case were distinguishable. This
      manuscript shows that CSIA when used in tandem with multivariate statistical
      analysis provide a defensible means to differentiate and source-apportion
      qualitatively similar oils at the molecular level. This approach was able to
      overcome confounding challenges posed by the near single-point source of origin,
      i.e., the very subtle differences in isotopic values between the samples. 

PMID- 25774367
TI  - Study of patients absconding behavior in a general hospital at southern region of
      Iran.
AB  - BACKGROUND: Patients' escape from hospital imposes a significant cost to patients
      as well as the health system. Besides, for these patients, exposure to adverse
      events (such as suicide, self-harm, violence and harm to hospital reputation) are
      more likely to occur compared to others. The present study aimed to determine the
      characteristics of the absconding patients in a general hospital through a case
      control design in Shiraz, Iran. METHODS: This case-control study was conducted on
      413 absconded patients as case and 413 patients as control in a large general
      hospital in Shiraz, southern Iran. In this study, data on the case and control
      patients was collected from the medical records using a standard checklist in the
      period of 2011-3. Then, the data were analyzed using descriptive and analytical
      statistics, through SPSS 16. RESULTS: The finding showed that 413 patients
      absconded (0.50%) and mean of age in case group was 40.98 +/- 16.31 years. In
      univariate analysis, variables of gender [Odds Ratio (OR)= 2], ward (OR= 1.22),
      insurance status (OR= 0.41), job status (OR= 0.34) and residence expenditure were
      significant. However, in multivariate analysis significant variables were age
      (ORadj= 0.13), gender (ORadj= 2.15), self-employment/unemployed (ORadj= 0.47),
      emergency/admission (ORadj= 2.14), internal/admission (ORadj= 3.16), insurance
      status (ORadj= 4.49) and residence expenditure (ORadj= 1.15). CONCLUSION:
      Characteristics such as middle age, male gender, no insurance coverage, inability
      to afford hospital expenditures and admission in emergency department make
      patients more likely abscond from the hospital. Therefore, it may be necessary to
      focus efforts on high-risk groups and increase insurance coverage in the country
      to prevent absconding from hospital.

PMID- 25774368
TI  - Translating evidence into healthcare policy and practice: Single versus multi
      faceted implementation strategies - is there a simple answer to a complex
      question?
AB  - How best to achieve the translation of research evidence into routine policy and
      practice remains an enduring challenge in health systems across the world. The
      complexities associated with changing behaviour at an individual, team,
      organizational and system level have led many academics to conclude that
      tailored, multi-faceted strategies provide the most effective approach to
      knowledge translation. However, a recent overview of systematic reviews questions
      this position and sheds doubt as to whether multi-faceted strategies are any
      better than single ones. In this paper, we argue that this either-or distinction
      is too simplistic and fails to recognize the complexity that is inherent in
      knowledge translation. Drawing on organizational theory relating to boundaries
      and boundary management, we illustrate the need for translational strategies that
      take account of the type of knowledge to be implemented, the context of
      implementation and the people and processes involved. 

PMID- 25774369
TI  - Knowledge mobilization in healthcare organizations: a view from the resource
      based view of the firm.
AB  - This short literature review argues that the Resource-Based View (RBV) school of
      strategic management has recently become of increased interest to scholars of
      healthcare organizations. RBV links well to the broader interest in more
      effective Knowledge Mobilization (KM) in healthcare. The paper outlines and
      discusses key concepts, texts and authors from the RBV tradition and gives recent
      examples of how RBV concepts have been applied fruitfully to healthcare settings.
      It concludes by setting out a future research agenda. 

PMID- 25774370
TI  - Situation of linkage between sexual and reproductive health and HIV-related
      policies in Islamic Republic of Iran - a rapid assessment in 2011-2.
AB  - The number of sexual transmission of HIV is increasing globally. Sexual and
      Reproductive Health (SRH) issues and HIV/AIDS related problems are rooted in
      common grounds such as poverty, gender inequality, and social exclusion. As a
      result, international health organizations have suggested the integration of SRH
      services with HIV/AIDS services as a strategy to control HIV and to improve
      people's access to SRH services. The aim of this study was to evaluate the
      relationship between reproductive health and HIV/AIDS services at policy-making
      level in Islamic Republic of Iran (IRI). This study was conducted in 2011-2 and
      was a rapid assessment based on guidelines provided by the World Health
      Organization (WHO), United Nations Programme on HIV/AIDS (UNAIDS), Family Health
      International Association, and some other international organizations. In this
      rapid assessment we used different methods such as a review of literature and
      documents, visiting and interviewing professionals and experts in family health
      and HIV/AIDS programs, and experts working in some Non-Governmental Organizations
      (NGOs). Overall, based on the results obtained in this study, in most cases there
      was not much linkage between HIV/AIDS policies and SRH policies in Iran. Since
      integration of HIV/AIDS services and SRH services is recommended as a model and
      an appropriate response to HIV epidemics worldwide, likewise to control the
      HIV/AIDS epidemic in Iran it is required to integrate HIV/AIDS and SRH services
      at all levels, particularly at the policy-making level. 

PMID- 25774371
TI  - Long and short Integrated Management of Childhood Illness (IMCI) training courses
      in Afghanistan: a cross-sectional cohort comparison of post-course knowledge and
      performance.
AB  - BACKGROUND: In 2003 the Afghan Ministry of Public Health (MoPH) adopted the
      Integrated Management of Childhood Illness (IMCI) for delivering child health
      services in primary care facilities. Key problems were subsequently identified:
      high cost of training, frequent health worker turnover and poor quality of IMCI
      implementation by those trained - specifically in the use of job aids and
      protocols for assessment, classification, treatment and counselling. The high
      financial, human resources and opportunity costs of implementing IMCI spurred the
      MoPH to prioritize developing a shortened IMCI course of comparable quality to
      the 11-Day training. METHODS: This cross-sectional evaluation compared knowledge
      before and after training, and health worker performance in assessment,
      classification and treatment of sick children in two similar cohorts, eight
      months post-training. RESULTS: The mean increase in knowledge scores of the
      thirty 7-Day course trainees was 29 [95% Confidence Interval (CI): 24, 34]
      compared to 23 (95% CI: 18, 28) in the 31 trained in the 11-Day course. During
      assessment visits, mean scores in the 7-Day course trainees and the 11-Day course
      trainees were 93% (95% CI: 91, 95) versus 94% (95% CI: 91, 96) in assessment; 95%
      (95% CI: 89, 100) versus 96% (95% CI: 91, 100) in classification; 95% (95% CI:
      92, 100) versus 97% (95% CI: 95, 100) in treatment; and 81% (95% CI: 76, 86)
      versus 80% (95% CI: 75, 85) in counselling. The 7-Day course was 36% less
      expensive than the 11-Day course. For each course opportunity costs, measured as
      numbers of children who potentially received poorer care than usual during
      trainee absence, were 3,160 for the 11-Day course and 2,016 for the 7-Day course.
      This measure was chosen because trainee absence commonly resulted in higher
      patient volumes per remaining provider or complete closure of a health facility
      with one single health worker. CONCLUSION: Given similar performance and
      knowledge of health workers trained in both courses, potential cost savings, the
      possibility of training more health workers and the relative ease with which
      health workers in remote settings might participate in a shorter course, it seems
      prudent to standardize the 7-Day course in Afghanistan where child mortality
      rates remain unacceptably high.

PMID- 25774372
TI  - Course of health care costs before and after psychiatric inpatient treatment:
      patient-reported vs. administrative records.
AB  - BACKGROUND: There is limited evidence on the course of health service costs
      before and after psychiatric inpatient treatment, which might also be affected by
      source of cost data. Thus, this study examines: i) differences in health care
      costs before and after psychiatric inpatient treatment, ii) whether these
      differences vary by source of cost-data (self-report vs. administrative), and
      iii) predictors of cost differences over time. METHODS: Sixty-one psychiatric
      inpatients gave informed consent to their statutory health insurance company to
      provide insurance records and completed assessments at admission and 6-month
      follow-up. These were compared to the self-reported treatment costs derived from
      the "Client Socio-demographic and Service Use Inventory" (CSSRI-EU) for two 6
      month observation periods before and after admission to inpatient treatment to a
      large psychiatric hospital in rural Bavaria. Costs were divided into subtypes
      including costs for inpatient and outpatient treatment as well as for medication.
      RESULTS: Sixty-one participants completed both assessments. Over one year, the
      average patient-reported total monthly treatment costs increased from ? 276.91 to
      ? 517.88 (paired Wilcoxon Z = -2.27; P = 0.023). Also all subtypes of treatment
      costs increased according to both data sources. Predictors of changes in costs
      were duration of the index admission and marital status. CONCLUSION: Self
      reported costs of people with severe mental illness adequately reflect actual
      service use as recorded in administrative data. The increase in health service
      use after inpatient treatment can be seen as positive, while the pre-inpatient
      level of care is a potential problem, raising the question whether more or better
      outpatient care might have prevented hospital admission. Findings may serve as a
      basis for future studies aiming at furthering the understanding of what to expect
      regarding appropriate levels of post-hospital care, and what factors may help or
      inhibit post-discharge treatment engagement. Future research is also needed to
      examine long-term effects of inpatient psychiatric treatment on outcome and
      costs.

PMID- 25774373
TI  - Implementation of a health policy advisory committee as a knowledge translation
      platform: the Nigeria experience.
AB  - BACKGROUND: In recent times, there has been a growing demand internationally for
      health policies to be based on reliable research evidence. Consequently, there is
      a need to strengthen institutions and mechanisms that can promote interactions
      among researchers, policy-makers and other stakeholders who can influence the
      uptake of research findings. The Health Policy Advisory Committee (HPAC) is one
      of such mechanisms that can serve as an excellent forum for the interaction of
      policy-makers and researchers. Therefore, the need to have a long term mechanism
      that allows for periodic interactions between researchers and policy-makers
      within the existing government system necessitated our implementation of a newly
      established HPAC in Ebonyi State Nigeria, as a Knowledge Translation (KT)
      platform. The key study objective was to enhance the capacity of the HPAC and
      equip its members with the skills/competence required for the committee to
      effectively promote evidence informed policy-making and function as a KT
      platform. METHODS: A series of capacity building programmes and KT activities
      were undertaken including: i) Capacity building of the HPAC using Evidence-to
      Policy Network (EVIPNet) SUPPORT tools; ii) Capacity enhancement mentorship
      programme of the HPAC through a three-month executive training programme on
      health policy/health systems and KT in Ebonyi State University Abakaliki; iii)
      Production of a policy brief on strategies to improve the performance of the
      Government's Free Maternal and Child Health Care Programme in Ebonyi State
      Nigeria; and iv) Hosting of a multi-stakeholders policy dialogue based on the
      produced policy brief on the Government's Free Maternal and Child Health Care
      Programme. RESULTS: The study findings indicated a noteworthy improvement in
      knowledge of evidence-to-policy link among the HPAC members; the elimination of
      mutual mistrust between policy-makers and researchers; and an increase in the
      awareness of importance of HPAC in the Ministry of Health (MoH). CONCLUSION:
      Findings from this study suggest that a HPAC can function as a KT platform and
      can introduce a new dimension towards facilitating evidence-to-policy link into
      the operation of the MoH, and can serve as an excellent platform to bridge the
      gap between research and policy.

PMID- 25774374
TI  - Addressing health workforce distribution concerns: a discrete choice experiment
      to develop rural retention strategies in Cameroon.
AB  - BACKGROUND: Nearly every nation in the world faces shortages of health workers in
      remote areas. Cameroon is no exception to this. The Ministry of Public Health
      (MoPH) is currently considering several rural retention strategies to motivate
      qualified health personnel to practice in remote rural areas. METHODS: To better
      calibrate these mechanisms and to develop evidence-based retention strategies
      that are attractive and motivating to health workers, a Discrete Choice
      Experiment (DCE) was conducted to examine what job attributes are most attractive
      and important to health workers when considering postings in remote areas. The
      study was carried out between July and August 2012 among 351 medical students,
      nursing students and health workers in Cameroon. Mixed logit models were used to
      analyze the data. RESULTS: Among medical and nursing students a rural retention
      bonus of 75% of base salary (aOR= 8.27, 95% CI: 5.28-12.96, P< 0.001) and
      improved health facility infrastructure (aOR= 3.54, 95% CI: 2.73-4.58)
      respectively were the attributes with the largest effect sizes. Among medical
      doctors and nurse aides, a rural retention bonus of 75% of base salary was the
      attribute with the largest effect size (medical doctors aOR= 5.60, 95% CI: 4.12
      7.61, P< 0.001; nurse aides aOR= 4.29, 95% CI: 3.11-5.93, P< 0.001). On the other
      hand, improved health facility infrastructure (aOR= 3.56, 95% CI: 2.75-4.60, P<
      0.001), was the attribute with the largest effect size among the state registered
      nurses surveyed. Willingness-to-Pay (WTP) estimates were generated for each
      health worker cadre for all the attributes. Preference impact measurements were
      also estimated to identify combination of incentives that health workers would
      find most attractive. CONCLUSION: Based on these findings, the study recommends
      the introduction of a system of substantial monetary bonuses for rural service
      along with ensuring adequate and functional equipment and uninterrupted supplies.
      By focusing on the analysis of locally relevant, actionable incentives, generated
      through the involvement of policy-makers at the design stage, this study provides
      an example of research directly linked to policy action to address a vitally
      important issue in global health.

PMID- 25774375
TI  - The use (or rather the non-use) of cost-effectiveness data in priority setting
      decisions - are we underestimating the barriers to using health economics in real
      world priority setting decisions?: Comment on "Use of cost-effectiveness data in
      priority setting decisions: experiences from the national guidelines for heart
      diseases in Sweden".
AB  - After having practicing and researching health economics for nearly 15 years now,
      it has become clear to me that the use of cost-effectiveness data in priority
      setting decisions is rather a rare than a common practice. The Eckard et al.
      article though, describes a wonderful exception to this rule and a very good
      example of how it can be used when the conditions are right. However, do we fully
      understand what these conditions are? In this commentary article I will address
      some of the institutional and cultural conditions that need to be fulfilled in
      order for cost-effectiveness data to actually be used in priority setting
      decisions. 

PMID- 25774376
TI  - Lonely at the top and stuck in the middle? The ongoing challenge of using cost
      effectiveness information in priority setting : Comment on "Use of cost
      effectiveness data in priority setting decisions: experiences from the national
      guidelines for heart diseases in Sweden".
AB  - The topic of how cost-effectiveness information informs priority setting in
      healthcare remains important to both policy and practice. This commentary
      considers the study carried out by Eckard and colleagues in Sweden. In it we
      distinguish between the conditions at national and local levels and put forward
      some recommendations for research into local priority setting in particular. 

PMID- 25774377
TI  - Health improvements for a healthy Shanghai rising: Comment on "Shanghai Rising:
      health improvements as measured by avoidable mortality since 2000".
AB  - The commentator suggests that it is necessary to extend the classical connotation
      of global city which focuses much on the functions of controlling global capital
      and production. Global city should also include the dimensions of the leading
      role and capacity on health improvements and well-being promotion. The
      commentator agrees with authors' assessments about Shanghai's substantial
      progress on health services and health system reform, however, we should pay much
      attention to the significant inequality of health services between central city
      and outskirt, and between local residents and non-hukou migrants. The commentator
      also suggests that future researches could study the successful experiences of
      Avoidable Mortality (AM) decline and also disease specific AM decline in main
      global cities, in order to make more effective policy implications and social
      schemes recommendations for health improvements in Shanghai and in other cities. 

PMID- 25774378
TI  - "Wood already touched by fire is not hard to set alight": Comment on "Constraints
      to applying systems thinking concepts in health systems: A regional perspective
      from surveying stakeholders in Eastern Mediterranean countries".
AB  - A major constraint to the application of any form of knowledge and principles is
      the awareness, understanding and acceptance of the knowledge and principles.
      Systems Thinking (ST) is a way of understanding and thinking about the nature of
      health systems and how to make and implement decisions within health systems to
      maximize desired and minimize undesired effects. A major constraint to applying
      ST within health systems in Low- and Middle-Income Countries (LMICs) would appear
      to be an awareness and understanding of ST and how to apply it. This is a
      fundamental constraint and in the increasing desire to enable the application of
      ST concepts in health systems in LMIC and understand and evaluate the effects; an
      essential first step is going to be enabling of a wide spread as well as deeper
      understanding of ST and how to apply this understanding. 

PMID- 25774379
TI  - The Chinese healthcare challenge: Comment on "Shanghai rising: avoidable
      mortality as measured by avoidable mortality since 2000".
AB  - Investments in the extension of health insurance coverage, the strengthening of
      public health services, as well as primary care and better hospitals, highlights
      the emerging role of healthcare as part of China's new growth regime, based on an
      expansion of services, and redistributive policies. Such investments, apart from
      their central role in terms of relief for low-income people, serve to rebalance
      the Chinese economy away from export-led growth toward the domestic market,
      particularly in megacity-regions as Shanghai and the Pearl River Delta, which
      confront the challenge of integrating migrant workers. Based on the paper by
      Gusmano and colleagues, one would expect improvements in population health for
      permanent residents of China's cities. The challenge ahead, however, is how to
      address the growth of inequalities in income, wealth and the social wage. 

PMID- 25774380
TI  - An ex vivo Model of HIV-1 Infection in Human Lymphoid Tissue and Cervico-vaginal
      Tissue.
AB  - Human tissue explants are a valuable tool to study the interactions between host
      and infectious agents. They reliably mimic many important aspects of tissue
      cytoarchitecture and functions and allow us the investigation of the mechanisms
      of microbial pathogenesis under controlled laboratory conditions. One of the
      advantages of this system is that, unlike isolated cells, infection of tissue
      blocks with HIV-1 does not require exogenous stimulation with mitogens or
      activating factors. Here we describe a protocol to infect with HIV-1 human
      lymphoid tissue from tonsils and cervico-vaginal tissue and maintain them in
      culture in a non-polarized setting. These ex vivo infected tissues can be used as
      fruitful models to study HIV-1 pathogenesis and HIV-1 vaginal transmission,
      respectively, as well as an efficient platform for testing anti-HIV therapeutic
      and preventative strategies.

PMID- 25774381
TI  - Utility of preoperative ferumoxtran-10 MRI to evaluate retroperitoneal lymph node
      metastasis in advanced cervical cancer: Results of ACRIN 6671/GOG 0233.
AB  - RATIONALE AND OBJECTIVES: To assess if ferumoxtran-10 (f-10) improves accuracy of
      MRI to detect lymph node (LN) metastasis in advanced cervical cancer. MATERIALS
      AND METHODS: F-10 MRI component of an IRB approved HIPAA compliant ACRIN/GOG
      trial was analyzed. Patients underwent f-10 MRI followed by extra-peritoneal or
      laparoscopic pelvic and abdominal lymphadenectomy. F-10-sensitive sequences were
      T2* GRE sequences with TE of 12 and 21. Seven independent blinded readers
      reviewed f-10-insensitive sequences and all sequences in different sessions.
      Region correlations were performed between pathology and MRI for eight abdomen
      and pelvis regions. Sensitivity and specificity were calculated at participant
      level. Reference standard is based on pathology result of surgically removed LNs.
      RESULTS: Among 43 women enrolled in the trial between September 2007 and November
      2009, 33 women (mean age 49 +/-11 years old) with advanced cervical cancer (12
      IB2, 3 IIA, 15 IIB and 3 IIIB, 29 squamous cell carcinomas, 32 grade 2 or 3) were
      evaluable. Based on histopathology, LN metastasis was 39% in abdomen and 70% in
      pelvis. Sensitivity of all sequence review in pelvis, abdomen, and combined were
      83%, 60%, and 86%, compared with 78%, 54%, and 80% for f-10 insensitive sequences
      (P: 0.24, 0.44 and 0.14, respectively). Mean diameter of the largest positive
      focus on histopathology was 13.7 mm in abdomen and 18.8 mm in pelvis (P = 0.018).
      Specificities of all sequence review in pelvis, abdomen, and combined were 48%,
      75%, and 43%, compared with 75%, 83%, and 73% (P: 0.003, 0.14, 0.002
      respectively) for f-10 insensitive sequences. CONCLUSION: Addition of f-10
      increased MRI sensitivity to detect LN metastasis in advanced cervical cancer.
      Increased sensitivity did not reach statistical significance and was at the
      expense of lower specificity.

PMID- 25774382
TI  - Thriving through relationships.
AB  - The specific pathways through which close relationships promote optimal well
      being are not well understood. We describe a model (building on attachment
      theory's notion of safe haven and secure base support) that explains how close
      relationships promote thriving. This model defines thriving, identifies distinct
      contexts through which individuals may thrive (life adversity and life
      opportunities for growth), describes two distinct social support functions in
      close relationships that promote thriving (source of strength support and
      relational catalyst support), and identifies mediators through which relational
      support leads to long-term thriving.

PMID- 25774384
TI  - CREG1 ameliorates myocardial fibrosis associated with autophagy activation and
      Rab7 expression.
AB  - In cardiomyocytes subjected to stress, autophagy activation is a critical
      survival mechanism that preserves cellular energy status while degrading damaged
      proteins and organelles. However, little is known about the mechanisms that
      govern this autophagic response. Cellular repressor of E1A genes (CREG1) is an
      evolutionarily conserved lysosomal protein, and an important new factor in
      regulating tissues homeostasis that has been shown to antagonize injury of
      tissues or cells. In the present study, we aimed to investigate the regulatory
      role of CREG1 in cardiac autophagy, and to clarify autophagy activation
      mechanisms. First, we generated a CREG1 haploinsufficiency (Creg1(+/-)) mouse
      model, and identified that CREG1 deficiency aggravates myocardial fibrosis in
      response to aging or angiotensin II (Ang II). Conversely, exogenous infusion of
      recombinant CREG1 protein complete reversed cardiac damage. CERG1 deficiency in
      Creg1(+/-) mouse heart showed a market accumulation of autophagosome that
      acquired LC3II and beclin-1, and a decrease in autophagic flux clearance as
      indicated by upregulating the level of p62. Inversely, restoration of CREG1
      activates cardiac autophagy, Furthermore, chloroquine, an inhibitor of lysosomal
      acidification, was used to confirm that CREG1 protected the heart tissue against
      Ang II-induced fibrosis by activating autophagy. Using adenoviral infection of
      primary cardiomyocytes, overexpression of CREG1 with concurrent resveratrol
      treatment significantly increased autophagy, while silencing CREG1 blocked the
      resveratrol-induced autophagy. These results suggest that CREG1-induced autophagy
      is required to maintain heart function in the face of stress-induced myocardiac
      damage. Both in vitro and in vivo studies identified that CREG1 deficiency
      influenced the maturation of lysosomes and reduced the espression of Rab7, which
      might be involved in CREG1-induced cardiomyocyte autophagy. These findings
      suggest that autophagy activation via CREG1 may be a viable therapeutic strategy
      autophagy for improving cardiac performance under pathologic conditions. This
      article is part of a Special Issue entitled: autophagy and protein quality
      control in cardiometabolic diseases.

PMID- 25774385
TI  - Oceans of plastic waste.

PMID- 25774383
TI  - Rare autism-associated variants implicate syntaxin 1 (STX1 R26Q) phosphorylation
      and the dopamine transporter (hDAT R51W) in dopamine neurotransmission and
      behaviors.
AB  - BACKGROUND: Syntaxin 1 (STX1) is a presynaptic plasma membrane protein that
      coordinates synaptic vesicle fusion. STX1 also regulates the function of
      neurotransmitter transporters, including the dopamine (DA) transporter (DAT). The
      DAT is a membrane protein that controls DA homeostasis through the high-affinity
      re-uptake of synaptically released DA. METHODS: We adopt newly developed animal
      models and state-of-the-art biophysical techniques to determine the contribution
      of the identified gene variants to impairments in DA neurotransmission observed
      in autism spectrum disorder (ASD). OUTCOMES: Here, we characterize two
      independent autism-associated variants in the genes that encode STX1 and the DAT.
      We demonstrate that each variant dramatically alters DAT function. We identify
      molecular mechanisms that converge to inhibit reverse transport of DA and DA
      associated behaviors. These mechanisms involve decreased phosphorylation of STX1
      at Ser14 mediated by casein kinase 2 as well as a reduction in STX1/DAT
      interaction. These findings point to STX1/DAT interactions and STX1
      phosphorylation as key regulators of DA homeostasis. INTERPRETATION: We determine
      the molecular identity and the impact of these variants with the intent of
      defining DA dysfunction and associated behaviors as possible complications of
      ASD.

PMID- 25774386
TI  - Natasha Raikhel.

PMID- 25774392
TI  - Mighty hearts in space.

PMID- 25774393
TI  - A tale of two threonines: myosin   phosphatase inhibition and   calcium
      sensitization of smooth   muscle.

PMID- 25774394
TI  - Brown adipose tissue--not as   hot as we thought.

PMID- 25774395
TI  - Age is just a number! Or is it?

PMID- 25774396
TI  - Preface. Chemical biology.

PMID- 25774398
TI  - Evidence-based review and discussion points.

PMID- 25774399
TI  - Reply from the author.

PMID- 25774397
TI  - Fluid shifts, vasodilatation and ambulatory blood pressure reduction during long
      duration spaceflight.
AB  - KEY POINTS: Weightlessness in space induces initially an increase in stroke
      volume and cardiac output, accompanied by unchanged or slightly reduced blood
      pressure.It is unclear whether these changes persist throughout months of
      flight.Here, we show that cardiac output and stroke volume increase by 35-41%
      between 3 and 6 months on the International Space Station, which is more than
      during shorter flights.Twenty-four hour ambulatory brachial blood pressure is
      reduced by 8-10 mmHg by a decrease in systemic vascular resistance of 39%, which
      is not a result of the suppression of sympathetic nervous activity, and the
      nightly dip is maintained in space.It remains a challenge to explore what causes
      the systemic vasodilatation leading to a reduction in blood pressure in space,
      and whether the unexpectedly high stroke volume and cardiac output can explain
      some vision acuity problems encountered by astronauts on the International Space
      Station. ABSTRACT: Acute weightlessness in space induces a fluid shift leading to
      central volume expansion. Simultaneously, blood pressure is either unchanged or
      decreased slightly. Whether these effects persist for months in space is unclear.
      Twenty-four hour ambulatory brachial arterial pressures were automatically
      recorded at 1-2 h intervals with portable equipment in eight male astronauts:
      once before launch, once between 85 and 192 days in space on the International
      Space Station and, finally, once at least 2 months after flight. During the same
      24 h, cardiac output (rebreathing method) was measured two to five times (on the
      ground seated), and venous blood was sampled once (also seated on the ground) for
      determination of plasma catecholamine concentrations. The 24 h average systolic,
      diastolic and mean arterial pressures (mean +/- se) in space were reduced by 8 +/
      2 mmHg (P = 0.01; ANOVA), 9 +/- 2 mmHg (P < 0.001) and 10 +/- 3 mmHg (P =
      0.006), respectively. The nightly blood pressure dip of 8 +/- 3 mmHg (P = 0.015)
      was maintained. Cardiac stroke volume and output increased by 35 +/- 10% and 41
      +/- 9% (P < 0.001); heart rate and catecholamine concentrations were unchanged;
      and systemic vascular resistance was reduced by 39 +/- 4% (P < 0.001). The
      increase in cardiac stroke volume and output is more than previously observed
      during short duration flights and might be a precipitator for some of the vision
      problems encountered by the astronauts. The spaceflight vasodilatation mechanism
      needs to be explored further.

PMID- 25774400
TI  - Reply from the author.

PMID- 25774401
TI  - [Tribute to Mervyn Susser].

PMID- 25774402
TI  - Why restraint is completely unnecessary in treatment.

PMID- 25774403
TI  - Washington state chips away at psychiatric boarding.

PMID- 25774404
TI  - Buprenorphine use remains hit or miss.

PMID- 25774405
TI  - Integrated facility offers seamless care to Denver's homeless.

PMID- 25774406
TI  - Overworked, under-resourced and worried about patient safety. Your heartfelt
      comments reveal the truth about job and service cuts..

PMID- 25774407
TI  - Ratios save lives. The volume of evidence is overwhelming, the time to act is
      NOW.

PMID- 25774408
TI  - EB9 negotiation delays a worrying sign for the future.

PMID- 25774409
TI  - Queenslanders can't risk a privatisation agenda.

PMID- 25774410
TI  - Three years of government sets health and safety back decades.

PMID- 25774411
TI  - Impact of a court-referred psychological treatment program for intimate partner
      batterer men with suspended sentences.
AB  - In this article, the impact of a court-mandated psychological treatment program
      for men who had committed an offense of intimate partner violence is tested. The
      sample consisted of 235 men who received a suspended sentence after being charged
      and sentenced for an offense in relation to intimate partner violence. The
      success rate in the posttreatment period was 37.4%, and the improvement rate was
      48.1%. Therefore, in 85.5% of cases, the treatment program was effective. Results
      after 12 months of follow-up were almost identical. Moreover, there was a
      significant decrease in associated psychopathological symptoms. Regarding
      prediction of therapeutic results, batterers who were older, who had more
      distorted thoughts about violence, and who had not been victims of childhood
      abuse were at a significantly greater risk of treatment failure.

PMID- 25774412
TI  - Help-seeking patterns among women experiencing intimate partner violence: do they
      forgo the criminal justice system if their adjudication wishes are not met?
AB  - Following a criminal case disposition, an intimate partner violence (IPV)
      victim's willingness to seek future police and prosecutorial assistance may
      depend on her prior experiences within the system. This longitudinal study
      examines the relationship between IPV victims' future help-seeking based on past
      experiences. We hypothesized women would return to the criminal justice system if
      their adjudication wishes corresponded with prosecutors' actions. Contrary to the
      hypothesis, results suggest women return to the criminal system and other venues
      even if prosecutors' actions do not correspond to their earlier stated wishes.
      This has important policy implications given pro-prosecution protocols that
      encourage adjudication regardless of a woman's participation.

PMID- 25774413
TI  - Links between the police response and women's psychological outcomes following
      intimate partner violence.
AB  - Virtually no research considers the psychological impact of institutional support
      for survivors of intimate partner violence (IPV). This study sought to fill this
      gap by examining associations between one component of institutional support--the
      police response--and posttraumatic stress disorder (PTSD) symptom severity and
      posttrauma appraisals (i.e., anger, fear, and self-blame) in a diverse sample of
      female IPV survivors (N = 236). Results indicated that a more negative police
      response, as operationalized by women's unmet expectations in relation to the
      police, was significantly associated with greater PTSD symptom severity in a very
      conservative test that involved controlling for personal resources and social
      support. Police response was not significantly associated with the tested
      posttrauma appraisals. Implications for policy and practice will be discussed.
      This study advances understanding of the psychological impact of the police
      response--one key component of institutional support.

PMID- 25774414
TI  - Sexual revictimization: the impact of attachment anxiety, accumulated trauma, and
      response to childhood sexual abuse disclosure.
AB  - It has been proposed that a complexity of personal, interpersonal, and
      environmental factors is related to sexual revictimization among childhood sexual
      abuse survivors. In this study, we investigated the relations between attachment
      dimensions, exposure to accumulated childhood traumas, reaction to childhood
      sexual abuse disclosure, and adult sexual revictimization. Participants were 60
      Israeli women with histories of childhood sexual abuse. Seventy percent of the
      women reported adult sexual revictimization. Revictimization was related to
      higher attachment anxiety but not to higher attachment avoidance. Revictimization
      was also related to emotional and physical child abuse but not to emotional and
      physical child neglect. Revictimization rates were higher among women who had
      received negative environmental responses following childhood sexual abuse
      disclosure than among women who had received supportive reactions and those who
      had not disclosed childhood sexual abuse at all. Findings were significant even
      after controlling for severity of childhood sexual abuse. The findings emphasize
      the role of various contextual-interpersonal factors on revictimization
      vulnerability among the survivors of childhood sexual abuse.

PMID- 25774415
TI  - Perceptions of sexual assault victims/survivors: the influence of sexual history
      and body weight.
AB  - The intersection between a woman's body weight and sexual history and the victim
      blaming attitudes of future health care providers was investigated. University
      undergraduate students (N = 91) enrolled in programs associated with the
      provision of health care read 1 of 4 patient files of a woman reporting a rape as
      well as 2 distracter files. Results showed that, for overweight rape
      victims/survivors, study participants' antifat attitudes were correlated with
      victim blaming attitudes. Male participants held the attacker significantly less
      responsible than did female participants if the victim/survivor had several
      previous sexual partners. Findings suggest that body weight should be considered
      as a contributing factor in attitudes toward rape victims/survivors, and the
      gender of the health care provider can be a factor in the post-assault treatment
      of overweight rape victims/survivors.

PMID- 25774416
TI  - Neighborhood firearm victimization rates and social capital over time.
AB  - Distribution of firearm victimization is not equal within cities. Victimization
      can persistently concentrate in a small number of neighborhoods, while others
      experience very little violence. Theorists have pointed to one possible
      explanation as the ability of groups to control violence using social capital.
      Researchers have shown this association at the U.S. county, state, and national
      levels. Few studies, however, have examined the relationship between neighborhood
      social capital and violence over time. This study uses longitudinal data to ask
      whether neighborhood social capital both predicts and is influenced by firearm
      victimization over 3 years in Philadelphia. The results of several regression
      analyses suggest that trusting others and firearm victimization are inversely
      related over time. Implications for neighborhood policy planning and social
      capital as a theoretical framework are discussed.

PMID- 25774417
TI  - Individual and interpersonal risk factors for physical intimate partner violence
      perpetration by biological sex and ethnicity.
AB  - Intimate partner violence (IPV) is a public health problem that reaches across
      age, sex, and ethnicity. In this study, we examined risk factors for physical IPV
      perpetration among young adult males and females from four ethnic groups. Data
      were taken from Waves 1-3 of the National Longitudinal Study of Adolescent Health
      (Add Health). The sample included 10,141 Wave 3 respondents (ages ranged from 18
      27 years old) who reported being in a current romantic relationship. Physical IPV
      perpetration was reported by 14.10% of White, 23.28% of Black, 18.82% of Latino,
      and 18.02% of Asian males. Physical IPV perpetration was reported by 19.01% of
      White, 24.80% of Black, 25.97% of Latina, and 19.21% of Asian females. Following
      an ecological framework, proximal risk factors at intrapersonal and interpersonal
      levels were included in the analyses. Despite finding fairly consistent
      percentage of physical IPV perpetration across sample groups, the risk factors
      for physical IPV perpetration were rather uncommon across sex and ethnicity. Only
      1 factor--psychological IPV perpetration toward a romantic partner--was
      consistently associated with physical IPV perpetration across all groups. Our
      findings have implications for tailoring prevention and intervention efforts
      toward risk factors of physical IPV perpetration that are uniquely associated
      with biological sex and ethnicity.

PMID- 25774418
TI  - Direct and indirect violence exposure: relations to depression for economically
      disadvantaged ethnic minority mid-adolescents.
AB  - Exposure to violence remains a considerable public health problem for adolescents
      in the United States. This cross-sectional study examined relative associations
      between exposure to violence in 3 different contexts (home, school, community)
      and depressive symptoms, using data from 233 11th-graders (predominantly
      economically disadvantaged Hispanic and African American students). Analyses
      examined the effects of victimization and witnessing violence in each context and
      those of cumulative violence exposure across contexts on depression, controlling
      for other risk factors. Both victimization and witnessing violence at home
      significantly predicted depression. Violence exposure in school and neighborhood
      was unrelated to the outcome. Witnessing violence was slightly more effective in
      predicting depression than victimization. Cumulative violence exposure was
      significantly related to depression in a linear fashion.

PMID- 25774419
TI  - A brief report on rape myth acceptance: differences between police officers, law
      students, and psychology students in the United Kingdom.
AB  - A common perception is that police officers hold very negative attitudes about
      rape victims. Therefore, the purpose of this article is to establish whether
      police officers do accept stereotypical rape myths at a higher level compared to
      members of other populations. There were 3 comparison samples, composed of police
      officers, law students, and psychology students, that completed the Illinois Rape
      Myth Acceptance scale. Male and female police officers accepted "she lied" myths
      at a higher level than the student samples. Student samples were found to accept
      2 types of rape myths ("she asked for it" and "he didn't meant to") at a higher
      level compared to police officers. No significant differences were found in the
      other 4 subfactors. Therefore, the pattern of results suggests that police
      officers do not adhere to stereotypical myths about rape victims more than do
      other populations.

PMID- 25774420
TI  - Personality predictors of driver vengeance.
AB  - The purpose of this study was to identify personality and individual difference
      measures related to driver vengeance, as measured by the Driver Vengeance
      Questionnaire (DVQ; Wiesenthal, Hennessy, & Gibson, 2000). There were 170
      undergraduate students who completed paper-and-pencil questionnaires including
      the DVQ and measures of narcissism, impulsivity, and trait driver stress. A
      hierarchical linear regressidn predicting DVQ score revealed that being male
      (beta = .25), narcissism (beta = .19), and trait driver stress (beta = .41) were
      significantly associated with vengeance. Impulsivity was significant in the third
      block of the regression but was not a significant predictor of vengeance in the
      final block. Interactions between gender and the individual difference measures
      were not significant. The final model accounted for 34% of the variance.
      Implications of the results and directions for future research are discussed.

PMID- 25774421
TI  - Interpersonal difficulties mediate the relationship between child sexual abuse
      and depression symptoms.
AB  - This study examined the influence of interpersonal functioning as a mediator in
      the relationship between child sexual abuse and depression symptoms, after
      accounting for the influence of child physical abuse. The research questions
      build on the existing knowledge base by examining mechanisms of adult adjustment
      among child sexual abuse survivors. In the current study, 2,892 young adult women
      (18-29 years old; M = 19.06) reported on child sexual and physical abuse, 5
      domains of interpersonal functioning, and depression symptoms. The results
      supported aggression, sensitivity, ambivalence, and lack of sociability as
      mediators in the relationship between child sexual abuse and depression symptoms.
      These results suggest that interpersonal difficulties related to hostility,
      emotional reactivity, inability to collaborate, and isolation may be of
      particular interest when understanding depression in child sexual abuse
      survivors. The findings support interpersonal problems as a key mechanism of
      depression symptoms following child sexual abuse and is even demonstrated when
      examining long-term outcomes and controlling for child physical abuse. The
      hypotheses and findings are discussed in the context of interpersonal
      psychotherapy for depression.

PMID- 25774422
TI  - Activity of ERK regulates mucin 3 expression and is involved in undifferentiated
      Caco-2 cell death induced by 3-oxo-C12-homoserine lactone.
AB  - The signal molecule, 3-oxo-C12-homoserine lactone (3-oxo-C12-HSL), is similar to
      a mammalian hormone in bacteria. Although most studies have examined the effects
      of high 3-oxo-C12-HSL concentrations (>200 MUM) on mammalian cellular functions
      because ~600 MUM 3-oxo-C12-HSL can be secreted in biofilms of Pseudomonas
      aeruginosa grown in vitro, we previously showed that a low 3-oxo-C12-HSL
      concentration (30 MUM) induces the apoptosis of undifferentiated Caco-2 cells
      through suppressing Akt activity. Here, we found that a low concentration of 3
      oxo-C12-HSL-activated ERK1/2 in undifferentiated Caco-2 cells. Incubating cells
      with the ERK pathway inhibitor U0126 for 30 min alleviated the mucin 3 (MUC3)
      expression suppressed by 3-oxo-C12-HSL, and the upregulation of MUC3 expression
      induced by a 48-h incubation with U0126-reduced cell death. Thus, altered MUC3
      expression caused by long-term attenuated ERK1/2 activity might correlate with
      the death of undifferentiated Caco-2 cells induced by 3-oxo-C12-HSL. 

PMID- 25774423
TI  - Preparation and Characteristic of Dextran-BSA Antibody and Establishment of its
      ELISA Immunoassay.
AB  - The enzyme-linked immunosorbent assay (ELISA) is a potential tool for the
      determination of dextran. In this study, dextran neoglycoprotein antigens were
      prepared by Reductive Amination method, and were confirmed by SDS-PAGE and free
      amino detection. The impact factors such as different oxidation degree of
      dextran, the conjugate reaction time to BSA were investigated. The best
      preparation conditions were obtained (n(dextran)/n(oxidant) of NaIO4 = 1/120, the
      reaction time of 24 h), and the antigen with best combination with standard was
      obtained. The antigens interacted with standard antibody and were evaluated
      through ELISA. The immunogen was immunized with white rabbits to obtained
      antibody, respectively. A general and broad class-specific ELISA immunoassay was
      developed for dextran detection according to ELISA theory. The optimized
      conditions of assay used coating antigen at 10 MUg/mL, reaction time of antibody
      and rabbit-anti-bovine IgG in 45 min, blocking reagents with 5% calf serum. The
      developed ELISA detection method with good linear and accuracy was put to use for
      quantitative analysis of dextran T40 in commercial sugarpractical for detection
      of dextran.

PMID- 25774424
TI  - Temperature and pressure dependent rate coefficients for the reaction of C2H4 +
      HO2 on the C2H4O2H potential energy surface.
AB  - The potential energy surface (PES) for reaction C2H4 + HO2 was examined by using
      the quantum chemical methods. All rates were determined computationally using the
      CBS-QB3 composite method combined with conventional transition state theory(TST),
      variational transition-state theory (VTST) and Rice-Ramsberger-Kassel
      Marcus/master-equation (RRKM/ME) theory. The geometries optimization and the
      vibrational frequency analysis of reactants, transition states, and products were
      performed at the B3LYP/CBSB7 level. The composite CBS-QB3 method was applied for
      energy calculations. The major product channel of reaction C2H4 + HO2 is the
      formation C2H4O2H via an OH(...)pi complex with 3.7 kcal/mol binding energy which
      exhibits negative-temperature dependence. We further investigated the reactions
      related to this complex, which were ignored in previous studies. Thermochemical
      properties of the species involved in the reactions were determined using the CBS
      QB3 method, and enthalpies of formation of species were compared with literature
      values. The calculated rate constants are in good agreement with those available
      from literature and given in modified Arrhenius equation form, which are
      serviceable in combustion modeling of hydrocarbons. Finally, in order to
      illustrate the effect for low-temperature ignition of our new rate constants, we
      have implemented them into the existing mechanisms, which can predict ethylene
      ignition in a shock tube with better performance. 

PMID- 25774425
TI  - An Analysis of the Concept of Partnership in the Couples Undergoing Infertility
      Treatment.
AB  - The elements of a partnership in the couples undergoing infertility treatment are
      not well understood. This article aims to fill the gap by using Rodger's
      evolutionary method of concept analysis. The attributes of the concept
      partnership that were identified are a process of joint hardship, sharing,
      intracouple communication, and mutual support. The antecedents are love and
      attraction for each other, agreement, and interpersonal skills. The consequences
      are marital benefit, improvement in psychological status, and quality of life. A
      middle-range model for partnership in relationship to infertile couples is
      proposed. The understanding of the phenomenon of partnership will enable the
      researchers to develop interventions, identify the appropriate assessment
      instruments, and to determine directions for future research on effort to support
      infertile couples through their hardship. 

PMID- 25774426
TI  - In your 20s it's quantity, in your 30s it's quality: the prognostic value of
      social activity across 30 years of adulthood.
AB  - Social connection, a leading factor in the promotion of health, well-being, and
      longevity, requires social knowledge and the capacity to cultivate intimacy. Life
      span development theorists have speculated that social information-seeking goals,
      emphasized at the beginning of early adulthood, give way to emotional closeness
      goals in later stages of early adulthood. Drawing on developmental theory (Baltes
      & Carstensen, 2003; Baltes, 1997), this 30-year prospective study assessed social
      activity at age 20 and age 30 with experience sampling methods, and psychosocial
      outcomes (social integration, friendship quality, loneliness, depression, and
      psychological well-being) at age 50. Results supported the hypothesis that the
      quantity (but not the quality) of social interactions at age 20, and the quality
      (but not the quantity) of social interactions at age 30 predict midlife
      psychosocial outcomes. Longitudinal structural models revealed that age-20
      interaction quantity had a direct, unmediated effect on age-50 social and
      psychological outcomes. The effects of age-20 interaction quality on midlife
      outcomes, on the other hand, were mediated by age-30 interaction quality. Our
      findings are consistent with the idea that selection and optimization serve
      important functions in early adulthood, and that engaging in developmentally
      appropriate social activity contributes to psychosocial adjustment in the decades
      that follow.

PMID- 25774427
TI  - Oscillatory theta activity during memory formation and its impact on overnight
      consolidation: a missing link?
AB  - Sleep has been shown to promote memory consolidation driven by certain
      oscillatory patterns, such as sleep spindles. However, sleep does not consolidate
      all newly encoded information uniformly but rather "selects" certain memories for
      consolidation. It is assumed that such selection depends on salience tags
      attached to the new memories before sleep. However, little is known about the
      underlying neuronal processes reflecting presleep memory tagging. The current
      study sought to address the question of whether event-related changes in spectral
      theta power (theta ERSP) during presleep memory formation could reflect memory
      tagging that influences subsequent consolidation during sleep. Twenty-four
      participants memorized 160 word pairs before sleep; in a separate laboratory
      visit, they performed a nonlearning control task. Memory performance was tested
      twice, directly before and after 8 hr of sleep. Results indicate that
      participants who improved their memory performance overnight displayed stronger
      theta ERSP during the memory task in comparison with the control task. They also
      displayed stronger memory task-related increases in fast sleep spindle activity.
      Furthermore, presleep theta activity was directly linked to fast sleep spindle
      activity, indicating that processes during memory formation might indeed reflect
      memory tagging that influences subsequent consolidation during sleep.
      Interestingly, our results further indicate that the suggested relation between
      sleep spindles and overnight performance change is not as direct as once
      believed. Rather, it appears to be mediated by processes beginning during
      presleep memory formation. We conclude that theta ERSP during presleep memory
      formation reflects cortico-hippocampal interactions that lead to a better long
      term accessibility by tagging memories for sleep spindle-related reprocessing. 

PMID- 25774428
TI  - Attention and temporal expectations modulate power, not phase, of ongoing alpha
      oscillations.
AB  - The perception of near-threshold visual stimuli has been shown to depend in part
      on the phase (i.e., time in the cycle) of ongoing alpha (8-13 Hz) oscillations in
      the visual cortex relative to the onset of that stimulus. However, it is
      currently unknown whether the phase of the ongoing alpha activity can be
      manipulated by top-down factors such as attention or expectancy. Using three
      variants of a cross-modal attention paradigm with constant predictable stimulus
      onsets, we examined if cues signaling to attend to either the visual or the
      auditory domain influenced the phase of alpha oscillations in the associated
      sensory cortices. Importantly, intermixed in all three experiments, we included
      trials without a target to estimate the phase at target presentation without
      contamination from the early evoked responses. For these blank trials, at the
      time of expected target and distractor onset, we examined (1) the degree of the
      uniformity in phase angles across trials, (2) differences in phase angle
      uniformity compared with a pretarget baseline, and (3) phase angle differences
      between visual and auditory target conditions. Across all three experiments, we
      found that, although the cues induced a modulation in alpha power in occipital
      electrodes, neither the visual condition nor the auditory cue condition induced
      any significant phase-locking across trials during expected target or distractor
      presentation. These results suggest that, although alpha power can be modulated
      by top-down factors such as attention and expectation, the phase of the ongoing
      alpha oscillation is not under such control. 

PMID- 25774429
TI  - An animal model (guinea pig) of ocular siderosis: histopathology, pharmacology,
      and electrophysiology.
AB  - PURPOSE: Ocular siderosis is a rare sight-threatening complication that occurs
      after a penetrating ocular injury by an iron-containing foreign body. The
      purposes of this study were to (i) investigate the histopathology,
      electrophysiology and iron levels/accumulation in ocular siderosis using an
      animal (Guinea pig) model and (ii) determine the appropriate timing for follow-up
      foreign body-removal surgery. MATERIALS AND METHODS: Thirty guinea pigs were
      divided into five groups (n = 6 animals/group). On day-1, an iron body was
      inserted into the vitreous of the right eye of all animals; the left eyes were
      left undisturbed and were used as controls. At the end of each week during the 5
      week study period, electroretinography (ERG) was performed on all animals in one
      of the five groups. Each animal in that group was sacrificed, after which both
      eyes were enucleated for histopathological and pharmacological evaluation of
      intraocular iron. RESULTS: Accumulated iron levels of study eyes were
      significantly higher than those of control eyes (135.13 and 13.55 MUg/g,
      respectively, p < 0.01). In addition, there was a significant decrease in
      electrophysiological responses of study eyes. During the first week, iron levels
      were higher in study eyes than control eyes, but neither histological iron
      accumulation nor decreased electrophysiological responses could be detected. By
      the end of the second week, increased iron accumulation was observed
      histologically in intraocular tissues, along with signs of retinal toxicity, as
      verified by decreased electrophysiological responses. CONCLUSIONS: The present
      study indicates that the 14th day after a penetrating eye injury by an iron
      containing intraocular foreign body represents a clinically critical threshold,
      after which structural damage to and functional alterations in ocular tissues
      occur.

PMID- 25774432
TI  - Simultaneous measurements of molecular forces and electro-optical properties of a
      confined 5CB liquid crystal film using a surface forces apparatus.
AB  - Using a surface forces apparatus (SFA), we studied the forces associated with the
      reorientation of molecules of a common nematic thermotropic liquid crystal, 4'-n
      pentyl-4-cyanobiphenyl (5CB), confined between two conducting (silver) surfaces
      and its optical behavior under the influence of electric fields with varying
      magnitudes and field directions. A transient attractive force was observed due to
      partial reorientations of the liquid crystal molecules and the flow of free ions,
      in addition to a stronger constant capacitance attraction between the silver
      surfaces. At the same time, the optical properties of the liquid crystals were
      observed perpendicular to the silver surfaces. Observations of shifts and
      fluctuations of the extraordinary wave of the (multiple beam) interference
      fringes measure the refractive index of the director component parallel to the
      surface, which is sensitive to tilt motion (or reorientation) of the liquid
      crystal molecules that provided details of the anisotropic orientations of the
      molecules and domains. Any lateral differential refractive index change is easily
      observed by optical microscopy. The optical microscope imaging showed that the
      changes in the optical properties are due to convective flow at domain boundaries
      of the liquid crystal molecules (and possible free ions) between the two charged
      surfaces. At low electric fields, propagation of domain boundaries was observed,
      while at higher electric fields, hexagonal patterns of flowing molecules were
      observed. The interplay of the force measurements and optical observations reveal
      a complex dynamic behavior of liquid crystals subjected to varying electric
      fields in confined spaces. 

PMID- 25774433
TI  - Crystallization-modulated nanoporous polymeric materials with hierarchical
      patterned surfaces and 3D interpenetrated internal channels.
AB  - Poly(oxymethylene)/poly(L-lactic acid) (POM/PLLA) blends are typical melt
      miscible binary systems. During isothermal crystallization at various
      temperatures, in the presence of amorphous PLLA chains, POM crystallizes into
      banded spherulites with different band spaces, which forms a continuous
      crystalline phase and serves as a sturdy frame in the final porous materials. On
      the other hand, the amorphous PLLA chains are simultaneously expelled out from
      POM crystal lamellae to generate the other continuous phase during the
      crystallization of POM. Consequently, the interpenetration of the POM lamellae
      and the amorphous PLLA phase construct a cocontinuous phase structure. All the
      PLLA constituents are fully included in the interlamellar or interfibrillar of
      POM crystals. Thus, nanoporous POM materials with hierarchical patterned surface
      and 3D interpenetrated internal channels have been successfully obtained by
      extracting the amorphous PLLA phase. It is further found that the POM crystal
      morphologies in the blends are much dependent on the crystallization conditions.
      Therefore, the hierarchical patterned structure and the size of internal channels
      (pore size) can be modulated by adjusting the crystallization conditions.

PMID- 25774434
TI  - Exposure of extensively farmed wild boars (Sus scrofa scrofa) to selected pig
      pathogens in Greece.
AB  - BACKGROUND: Increased density and distribution of wild boar populations are
      likely to promote interactions and transmission of certain pathogens, not only
      among wild boar but also from wild boar to livestock or humans and vice versa.
      OBJECTIVE: The purpose of this study was to determine seroprevalence against
      seven selected pathogens in wild boar living in four different areas in Greece.
      ANIMALS AND METHODS: In total, 359 serum samples were collected from extensively
      farmed wild boar (Sus scrofa scrofa) originating from four distinct geographical
      areas throughout Greece from April 2012 to August 2013. Samples were tested for
      antibodies to Actinobacillus pleuropneumoniae, African swine fever virus (ASFV),
      Aujeszky's disease virus (ADV), classical swine fever virus (CSFV),
      Erysipelothrix rhusiopathiae, Mycoplasma hyopneumoniae and porcine reproductive
      and respiratory syndrome virus (PRRSV). Prevalence was compared among the four
      regions using Fisher's exact test. RESULTS: Low overall seropositivities of 2.4%
      and 5.6% were detected for E. rhusiopathiae and PRRSV, respectively, higher ones
      for ADV (32.0%) and the highest (72.5% and 90.5%) for M. hyopneumoniae and A.
      pleuropneumoniae, respectively. All sera tested were found negative for
      antibodies directed against CSFV and ASFV. CONCLUSIONS: This is the first report
      of exposure of wild boars to selected pig pathogens in Greece. These results are
      indicative of the circulation of these pathogens in Greece with the exception of
      CSFV and ASFV and suggestive of the potential role of wild boars on their
      maintenance and transmission to their domestic counterparts and vice versa.

PMID- 25774435
TI  - Highly dispersed CeO2 on TiO2 nanotube: a synergistic nanocomposite with superior
      peroxidase-like activity.
AB  - In this report, a novel nanocomposite of highly dispersed CeO2 on a TiO2 nanotube
      was designed and proposed as a peroxidase-like mimic. The best peroxidase-like
      activity was obtained for the CeO2/nanotube-TiO2 when the molar ratio of Ce/Ti
      was 0.1, which was much higher than that for CeO2/nanowire-TiO2, CeO2/nanorod
      TiO2, or CeO2/nanoparticle-TiO2 with a similar molar ratio of Ce/Ti. Moreover, in
      comparison with other nanomaterial based peroxidase mimics, CeO2/nanotube-TiO2
      nanocomposites exhibited higher affinity to H2O2 and 3,3',5,5'
      tetramethylbenzidine (TMB). Kinetic analysis indicated that the catalytic
      behavior was in accordance with typical Michaelis-Menten kinetics. Ce(3+) sites
      were confirmed as the catalytic active sites for the catalytic reaction. The
      first interaction of surface CeO2 with H2O2 chemically changed the surface state
      of CeO2 by transforming Ce(3+) sites into surface peroxide species causing
      adsorbed TMB oxidation. Compared with CeO2/nanowire-TiO2, CeO2/nanorod-TiO2, and
      CeO2/nanoparticle-TiO2, the combination of TiO2 nanotube with CeO2 presented the
      highest concentration of Ce(3+) thus leading to the best peroxidase-like
      activity. On the basis of the high activity of CeO2/nanotube-TiO2, the reaction
      provides a simple method for colorimetric detection of H2O2 and glucose with the
      detection limits of 3.2 and 6.1 MUM, respectively. 

PMID- 25774436
TI  - Hyperpolarized 15N-pyridine derivatives as pH-sensitive MRI agents.
AB  - Highly sensitive MR imaging agents that can accurately and rapidly monitor
      changes in pH would have diagnostic and prognostic value for many diseases. Here,
      we report an investigation of hyperpolarized (15)N-pyridine derivatives as
      ultrasensitive pH-sensitive imaging probes. These molecules are easily polarized
      to high levels using standard dynamic nuclear polarization (DNP) techniques and
      their (15)N chemical shifts were found to be highly sensitive to pH. These probes
      displayed sharp (15)N resonances and large differences in chemical shifts
      (Deltadelta > 90 ppm) between their free base and protonated forms. These
      favorable features make these agents highly suitable candidates for the detection
      of small changes in tissue pH near physiological values.

PMID- 25774437
TI  - Developmental neuropsychological assessment of 4- to 5-year-old children born
      following Preimplantation Genetic Diagnosis (PGD): A pilot study.
AB  - The purpose of this pilot study was to evaluate developmental neuropsychological
      profiles of 4- to 5-year-old children born after Preimplantation Genetic
      Diagnosis (PGD). Twenty-seven participants received a neurological examination
      and a battery of neuropsychological assessments including Wechsler Preschool &
      Primary Scale of Intelligence - Third Edition (WPPSI-III; cognitive development),
      Preschool Language Scale, Fourth Edition (PLS-4; language development), Wide
      Range Assessment of Visual Motor Abilities (visual motor abilities), Childhood
      Autism Rating Scales II (a screening test for autistic spectrum disorders), and
      the Miles ABC Test (ocular dominance). Parental questionnaires included the
      Behavior Rating Inventory of Executive Function Preschool Version (BRIEF-P;
      executive function), Child Behavior Checklist (CBCL) and the Carey Temperament
      Scales Behavioral Style Questionnaire (socioemotional development and
      temperament), and the Vineland Adaptive Behavior Scales, Interview Edition,
      Second Edition (general adaptive behavior). Subjects' tests results were compared
      to each test's norms. Children born after PGD demonstrated scores within the
      normal or above-normal ranges for all developmental outcomes (mean +/- SD): WPPSI
      III-VIQ 107.4 +/- 14.4 (p = .013), PLS-4-Total 113.2 +/- 12.4, p < .001), CBCL
      Total 41.1 +/- 8.6 (p < .001), BRIEF-P-Global Executive Composite 44.8 +/- 9.5 (p
      = .009). Twelve (44%) of the PGD children had a significant difference between
      their VIQ and PIQ scores (compared to 27% in the general population). One subject
      was found to show possible signs of autistic spectrum disorder, although a family
      history of autism was noted. In conclusion, in this pilot study, children
      assessed at age 4-5 years and conceived after PGD displayed developmental
      neuropsychological outcomes within normal limits as compared to their chronologic
      peers. A larger study is needed to evaluate and follow the neuropsychological
      development of children born after PGD.

PMID- 25774438
TI  - Further development of the talent development environment questionnaire for
      sport.
AB  - Given the significance of monitoring the critical environmental factors that
      facilitate athlete performance, this two-phase research aimed to validate and
      refine the revised talent development environment questionnaire (TDEQ). The TDEQ
      is a multidimensional self-report scale that assesses talented athletes'
      environmental experiences. Study 1 (the first phase) involved the examination of
      the revised TDEQ through an exploratory factor analysis (n = 363). This
      exploratory investigation identified a 28-item five-factor structure (i.e., TDEQ
      5) with adequate internal consistency. Study 2 (the second phase) examined the
      factorial structure of the TDEQ-5, including convergent validity, discriminant
      validity, and group invariance (i.e., gender and sports type). The second phase
      was carried out with 496 talented athletes through the application of
      confirmatory factor analyses and multigroup invariance tests. The results
      supported the convergent validity, discriminant validity, and group invariance of
      the TDEQ-5. In conclusion, the TDEQ-5 with 25 items appears to be a reliable and
      valid scale for use in talent development environments. 

PMID- 25774439
TI  - Authors' Reply: Evaluation of Paraoxonase 1 Activity in Chronic Obstructive
      Pulmonary Disease.

PMID- 25774440
TI  - Predictions instead of panics: the framework and utility of systematic
      forecasting of novel psychoactive drug trends.
AB  - BACKGROUND: Countless novel psychoactive substances have been sensationally
      described in the last 15 years by the media and academia. Though some become
      significant issues, most fail to become a substantial threat. The diversity and
      breadth of these potential problem substances has led policymakers, law
      enforcement officers, and healthcare providers alike to feel overwhelmed and
      underprepared for dealing with novel drugs. OBJECTIVE: Inadequacies in training
      and preparation may be remedied by a response that is more selective and more
      proactive. The current manuscript seeks to clarify how to most efficiently
      forecast the "success" of each newly introduced novel psychoactive substance in
      order to allow for more efficient decision making and proactive resource
      allocation. METHODS: A review of literature, published case reports, and legal
      studies was used to determine which factors were most closely linked to use of a
      novel drug spreading. Following the development of a forecasting framework,
      examples of its use are provided. RESULTS: The resulting five-step forecast
      method relies on assessments of the availability of a potential user base, the
      costs--legal and otherwise--of the drug relative to existent analogues, the
      subjective experience, the substance's dependence potential and that of any
      existent analogue, and ease of acquisition. These five factors should serve to
      forecast the prevalence of novel drug use, but reaction should be conditioned by
      the potential for harm. CONCLUSIONS: The five-step forecast method predicts that
      use of acetyl fentanyl, kratom, Leonotis leonurus, and e-cigarettes will grow,
      but that use of dragonfly and similar substances will not. While this forecasting
      approach should not be used as a replacement for monitoring, the use of the five
      step method will allow policymakers, law enforcement and practitioners to quickly
      begin targeted evaluative, intervention, and treatment initiatives only for those
      drugs with predicted harm.

PMID- 25774441
TI  - Phrenic Nerve Conduction Abnormalities Correlate with Diaphragmatic Descent in
      Chronic Obstructive Pulmonary Disease.
AB  - Diaphragmatic weakness in chronic obstructive pulmonary disease (COPD) is
      ascribed to hyperinflation-induced diaphragm shortening as well as impairment in
      cellular and subcellular structures. Although phrenic neuropathy is known to
      cause diaphragmatic weakness, phrenic neuropathy is rarely considered in COPD.
      This work aimed at assessing phrenic nerve conduction in COPD and its relation to
      radiographic hyperinflation and pulmonary function. PATIENTS AND METHODS: Forty
      COPD patients were evaluated. Radiographic parameters of lung hyperinflation were
      measured on postero-anterior and lateral chest x-ray films. Flow volume loop
      parameters were obtained from all patients. Motor conduction study of the phrenic
      nerves was performed and potentials were recorded over the xiphoid process and
      the ipsilateral 7th intercostal space. Twenty-seven healthy subjects were
      enrolled as controls. RESULTS: Parameters of phrenic nerve conduction differed
      significantly in patients compared to controls. Phrenic nerve abnormalities were
      detected in 17 patients (42.5%). Electrophysiological measures correlated with
      diaphragmatic angle of depression on lateral view films and with lung height on
      postero-anterior films. They did not correlate with the flow volume loop data or
      disease severity score. CONCLUSION: Phrenic nerve conduction abnormality is an
      appreciated finding in COPD. Nerve stretching associated with diaphragmatic
      descent can be a suggested mechanism for nerve lesion. The presence of phrenic
      neuropathy may be an additional contributing factor to diaphragmatic dysfunction
      in COPD patients.

PMID- 25774442
TI  - Naringenin and quercetin--potential anti-HCV agents for NS2 protease targets.
AB  - Nonstructural proteins of hepatitis C virus had drawn much attention for the
      scientific fraternity in drug discovery due to its important role in the disease.
      3D structure of the protein was predicted using molecular modelling protocol.
      Docking studies of 10 medicinal plant compounds and three drugs available in the
      market (control) with NS2 protease were employed by using rigid docking approach
      of AutoDock 4.2. Among the molecules tested for docking study, naringenin and
      quercetin revealed minimum binding energy of - 7.97 and - 7.95 kcal/mol with NS2
      protease. All the ligands were docked deeply within the binding pocket region of
      the protein. The docking study results showed that these compounds are potential
      inhibitors of the target; and also all these docked compounds have good
      inhibition constant, vdW+Hbond+desolv energy with best RMSD value.

PMID- 25774443
TI  - Pathological postpartum breast engorgement: prediction, prevention, and
      resolution.
AB  - BACKGROUND: Severe breast engorgement can cause substantial discomfort for
      mothers and interfere with an infant's ability to feed at the breast. This study
      explored the possibility of prediction of pathological postpartum breast
      engorgement in lactating women in relation to intense breast engorgement at the
      end of the luteal phase of the menstrual cycle and the possibility of prevention
      and resolution of postpartum breast engorgement with expression with a breast
      pump of colostrum before the appearance of transitional milk. SUBJECTS AND
      METHODS: The first group included 70 women with pathological postpartum breast
      engorgement. The second group included 52 postpartum women, with 24 women having
      colostrum extracted by the breast pump from each breast once or twice for a
      duration of 20-25 minutes sequentially in the first 2-3 days after delivery in
      addition to the removal of colostrum by the baby, before engorgement developed.
      Twenty-eight women had colostrum removed only by the baby. The degree of breast
      engorgement was assessed using the previously published Robson four-level scale.
      RESULTS: Of the 70 patients with severe postpartum engorgement studied in the
      first group, 90% showed intense breast engorgement in the late luteal phase of
      the menstrual cycle. Expression of colostrum milk in the first experimental group
      from each breast eliminated excessive breast engorgement in breastfeeding
      mothers. CONCLUSIONS: Presence of intense breast engorgement at the end of the
      luteal phase of the menstrual cycle may be one of the most important indicators
      useful for predicting severe postpartum breast engorgement. Extraction of
      colostrum before the appearance of transitional milk lowers the risk of excessive
      engorgement in breastfeeding women.

PMID- 25774444
TI  - A systematic review of patient medication error on self-administering medication
      at home.
AB  - INTRODUCTION: Medication errors have been analyzed as a health professionals'
      responsibility (due to mistakes in prescription, preparation or dispensing).
      However, sometimes, patients themselves (or their caregivers) make mistakes in
      the administration of the medication. The epidemiology of patient medication
      errors (PEs) has been scarcely reviewed in spite of its impact on people, on
      therapeutic effectiveness and on incremental cost for the health systems. AREAS
      COVERED: This study reviews and describes the methodological approaches and
      results of published studies on the frequency, causes and consequences of
      medication errors committed by patients at home. A review of research articles
      published between 1990 and 2014 was carried out using MEDLINE, Web-of-Knowledge,
      Scopus, Tripdatabase and Index Medicus. EXPERT OPINION: The frequency of PE was
      situated between 19 and 59%. The elderly and the preschooler population
      constituted a higher number of mistakes than others. The most common were:
      incorrect dosage, forgetting, mixing up medications, failing to recall
      indications and taking out-of-date or inappropriately stored drugs. The majority
      of these mistakes have no negative consequences. Health literacy, information and
      communication and complexity of use of dispensing devices were identified as
      causes of PEs. Apps and other new technologies offer several opportunities for
      improving drug safety.

PMID- 25774445
TI  - Update on the management of the liver transplant patient.
AB  - PURPOSE OF REVIEW: To review and highlight recent literature regarding the
      medical management of adult patients undergoing liver transplantation. RECENT
      FINDINGS: The addition of serum sodium concentration to the model for end-stage
      liver disease (MELD) score more accurately predicts 90-day waitlist mortality.
      Predictors of waitlist mortality and posttransplant survival include lower
      albumin and the presence of ascites, varices, and encephalopathy, as well as more
      nontraditional predictors such as older age, obesity, frailty, and sarcopenia.
      Indications for liver transplantation are evolving with the advent of effective
      therapy for hepatitis C and the increased prevalence of nonalcoholic
      steatohepatitis. Disparities persist in the current allocation system, including
      geographic variation and MELD inflation for hepatocellular carcinoma. Share 35
      allows for broader regional sharing of organs for patients with the highest need,
      without detrimental effects on waitlist mortality or survival. Everolimus is a
      recently approved option for posttransplant immunosuppression that spares renal
      function. SUMMARY: The MELD score has enabled the liver transplant community to
      equitably allocate organs. Recent literature has focused on the limitations of
      the MELD score and the disparities inherent in the current system. The next steps
      for liver transplantation will be to develop strategies to further optimize
      waitlist prioritization and organ allocation.

PMID- 25774447
TI  - Reusable self-healing hydrogels realized via in situ polymerization.
AB  - In this work, a self-healing hydrogel has been prepared using in situ
      polymerization of acrylic acid and acrylamide in the presence of glycogen. The
      hydrogel was characterized using NMR, SEM, FT-IR, rheology, and dynamic light
      scattering (DLS) studies. The developed hydrogel exhibits self-healing properties
      at neutral pH, high swelling ability, high elasticity, and excellent mechanical
      strength. The hydrogel exhibits modulus values (G', G") as high as 10(6) Pa and
      shows an exceptionally high degree of swelling ratio (~3.5 * 10(3)). Further, the
      polymer based hydrogel adsorbs toxic metal ions (Cd(2+), Pb(2+), and Hg(2+)) and
      organic dyes (methylene blue and methyl orange) from contaminated water with
      remarkable efficiency (90-98%). The mechanistic analysis indicated the presence
      of pseudo-second-order reaction kinetics. The reusability of the hydrogel has
      been demonstrated by repeating the adsorption-desorption process over five cycles
      with identical results in the adsorption efficiency.

PMID- 25774446
TI  - Nonalcoholic fatty liver disease: new treatments.
AB  - PURPOSE OF REVIEW: Nonalcoholic fatty liver disease is the most common cause of
      liver dysfunction in the western world because of its close association with
      obesity, insulin resistance and dyslipidaemia. Nonalcoholic steatohepatitis
      (NASH) is a particular health concern due to the increased morbidity and
      mortality associated with progressive disease. At present, without specific
      targeted pharmacological therapies, the mainstay of therapy remains weight loss
      through dietary modification and lifestyle change; thus, the purpose of this
      review is to summarize the recent evidence for current and emerging therapies in
      NASH. RECENT FINDINGS: Some existing medications, including pioglitazones and
      angiotensin receptor antagonists, may be repurposed to help treat this condition.
      Vitamin E may improve histology in NASH, but safety issues limit its use.
      Recently, a number of novel agents specifically targeting nonalcoholic fatty
      liver disease pathogenesis have entered clinical trials, including the farnesoid
      X receptor agonist obeticholic acid, which has shown significant histological
      improvements in steatohepatitis and fibrosis. SUMMARY: Diet/lifestyle
      modification remains the mainstay of treatment. For patients with NASH and
      advanced fibrosis, current liver-directed pharmacotherapy with vitamin E and
      pioglitazone offer some benefits; obeticholic acid appears promising and is
      currently being tested. Comorbidities must be diagnosed and treated;
      cardiovascular disease remains a primary cause of death in these patients.

PMID- 25774448
TI  - Engineering nanoscale surface features to sustain microparticle rolling in flow.
AB  - Nanoscopic features of channel walls are often engineered to facilitate
      microfluidic transport, for instance when surface charge enables electro-osmosis
      or when grooves drive mixing. The dynamic or rolling adhesion of flowing
      microparticles on a channel wall holds potential to accomplish particle sorting
      or to selectively transfer reactive species or signals between the wall and
      flowing particles. Inspired by cell rolling under the direction of adhesion
      molecules called selectins, we present an engineered platform in which the
      rolling of flowing microparticles is sustained through the incorporation of
      entirely synthetic, discrete, nanoscale, attractive features into the nonadhesive
      (electrostatically repulsive) surface of a flow channel. Focusing on one example
      or type of nanoscale feature and probing the impact of broad systematic
      variations in surface feature loading and processing parameters, this study
      demonstrates how relatively flat, weakly adhesive nanoscale features, positioned
      with average spacings on the order of tens of nanometers, can produce sustained
      microparticle rolling. We further demonstrate how the rolling velocity and travel
      distance depend on flow and surface design. We identify classes of related
      surfaces that fail to support rolling and present a state space that identifies
      combinations of surface and processing variables corresponding to transitions
      between rolling, free particle motion, and arrest. Finally we identify
      combinations of parameters (surface length scales, particle size, flow rates)
      where particles can be manipulated with size-selectivity. 

PMID- 25774449
TI  - End-of-Life Care in Nursing Homes with Greater versus Less Palliative Care
      Knowledge and Practice.
AB  - BACKGROUND: Many older adults in nursing homes (NHs) lack palliative care (PC)
      access; but little is known about whether access to PC knowledge and practice
      (beyond hospice) impacts residents' care. OBJECTIVE: The study objective was to
      evaluate how differing levels of NH PC knowledge and practice are associated with
      residents' end-of-life health care use. METHODS: In 2009/10 we surveyed a
      stratified random sample of U.S. NHs and asked directors of nursing (DONs) PC
      knowledge and practice questions from Thompson and colleagues' validated PC
      Survey. This study includes 1981 NHs with complete survey responses and the
      58,876 residents who died in these facilities between July 2009 and June 2010.
      Medicare resident assessment (minimum data set [MDS]) and claims data from July
      2009 through June 2010 were used to determine outcomes and a NH's hospice use.
      Multivariate logistic regressions examined whether residing in NHs with higher PC
      scores was associated with documented six-month prognoses and receipt of
      aggressive treatments, including hospital and emergency room (ER) use in the last
      30 days of life. RESULTS: Controlling for NH hospice use, being in a NH with
      higher PC care knowledge scores was associated with residents having a higher
      likelihood of documented six-month prognoses and lower likelihoods of having
      feeding tubes, injections, restraints, suctioning, and end-of-life hospital and
      ER use. Being in a NH with higher PC practice scores was associated with a lower
      likelihood of having feeding tubes and ER visits. CONCLUSION: Policies and
      advocacy promoting the development of NH PC knowledge and practices could
      potentially improve care and reduce hospital and ER use.

PMID- 25774450
TI  - Retrieval induces adaptive forgetting of competing memories via cortical pattern
      suppression.
AB  - Remembering a past experience can, surprisingly, cause forgetting. Forgetting
      arises when other competing traces interfere with retrieval and inhibitory
      control mechanisms are engaged to suppress the distraction they cause. This form
      of forgetting is considered to be adaptive because it reduces future
      interference. The effect of this proposed inhibition process on competing
      memories has, however, never been observed, as behavioral methods are 'blind' to
      retrieval dynamics and neuroimaging methods have not isolated retrieval of
      individual memories. We developed a canonical template tracking method to
      quantify the activation state of individual target memories and competitors
      during retrieval. This method revealed that repeatedly retrieving target memories
      suppressed cortical patterns unique to competitors. Pattern suppression was
      related to engagement of prefrontal regions that have been implicated in
      resolving retrieval competition and, critically, predicted later forgetting.
      Thus, our findings demonstrate a cortical pattern suppression mechanism through
      which remembering adaptively shapes which aspects of our past remain accessible.

PMID- 25774452
TI  - Direct admission to hospitals among children in the United States.

PMID- 25774453
TI  - Severe, very early onset pre-eclampsia associated with liquorice consumption.
AB  - BACKGROUND: We present the case of very early onset pre-eclampsia, possibly
      aggravated by liquorice consumption. CASE: An 18-year-old healthy primigravida
      presented with high blood pressure and proteinuria at 18 weeks gestation. She had
      a strong family history of pre-eclampsia and was consuming considerable amounts
      of liquorice. A diagnosis of severe pre-eclampsia/hemolysis, elevated liver
      enzymes, and low platelet count was confirmed. The pregnancy was terminated.
      Extensive investigation ruled out underlying diseases and autopsy revealed a
      normal fetus. In three consequtive pregnancies, she developed milder forms of pre
      eclampsia. CONCLUSION: In healthy women with a familial/genetic susceptibility
      for pre-eclampsia, liquorice consumption may aggravate the course of the disease.

PMID- 25774451
TI  - Role of Tet1 and 5-hydroxymethylcytosine in cocaine action.
AB  - Ten-eleven translocation (TET) enzymes mediate the conversion of 5-methylcytosine
      (5mC) to 5-hydroxymethylcytosine (5hmC), which is enriched in brain, and its
      ultimate DNA demethylation. However, the influence of TET and 5hmC on gene
      transcription in brain remains elusive. We found that ten-eleven translocation
      protein 1 (TET1) was downregulated in mouse nucleus accumbens (NAc), a key brain
      reward structure, by repeated cocaine administration, which enhanced behavioral
      responses to cocaine. We then identified 5hmC induction in putative enhancers and
      coding regions of genes that have pivotal roles in drug addiction. Such induction
      of 5hmC, which occurred similarly following TET1 knockdown alone, correlated with
      increased expression of these genes as well as with their alternative splicing in
      response to cocaine administration. In addition, 5hmC alterations at certain loci
      persisted for at least 1 month after cocaine exposure. Together, these reveal a
      previously unknown epigenetic mechanism of cocaine action and provide new insight
      into how 5hmC regulates transcription in brain in vivo.

PMID- 25774454
TI  - Gender roles and perceptions of malaria risk in agricultural communities of Mwea
      Division in Central Kenya.
AB  - We examined gender differences in the perception of high malaria risk in women
      and factors associated with a high number of malaria episodes in the Mwea
      Division of Central Kenya. Ethnographic and successive free listing interviews
      (an open-ended data collection technique used to show the relation of items in a
      given domain) with 53 key informants and structured interviews conducted from
      June to October 2010 with 250 respondents who represented the socioeconomic and
      geographical diversity of the area were analyzed. Qualitative text analysis and
      inferential statistics were employed. While a greater proportion of men (51.6%)
      attributed women's high malaria risk to their "biological weakness," most women
      believed that their high malaria risk was related to their role in the
      agricultural fields (43.6%) and to their household responsibilities (23.1%).
      Compared to men, women were more likely to work in wet aspects of agricultural
      activities (chi(2) (2, N = 153) = 13.47, p < .01). Women were nearly twice as
      likely as men to report high episodes of malaria (adjusted odds ratio: 2.54; 95%
      confidence interval: 1.05-6.15). Culturally prescribed gender roles in
      agricultural communities in Mwea may play an important role in explaining
      disparity in reported malaria incidence. While identification of ecological and
      economic determinants of malaria is important, gender-based research can make a
      significant contribution to the development of effective and sustainable malaria
      reduction strategies. 

PMID- 25774455
TI  - Expression patterns of immune-associated genes in external genital and perianal
      warts treated with sinecatechins.
AB  - The role of human papillomavirus (HPV) in human disease includes external genital
      and perianal warts (EGW), with some HPV genotypes having oncogenic potential
      (i.e., HPV-16 and -18). While green-tea extracts have antitumor and
      antiproliferative effects in vitro, the mechanism of action of sinecatechins in
      the treatment of EGW is not well understood. To investigate the role of immune
      regulated genes further, an open-label, single institution, prospective study was
      conducted enrolling patients with clinically diagnosed EGW. Thirty subjects were
      enrolled, and 18 completed the trial. All patients applied sinecatechins 15%
      ointment to target lesions in the study. RNA expression microarrays were obtained
      from treated EGW lesions and analyzed for differential gene expression of immune
      regulated genes. HPV types were analyzed and, based on copy number, were
      stratified into virological responders (VR) or nonresponders (VNR). Gene
      expression analysis of RNA samples was performed using TaqMan arrays for human T
      cell receptor and CD3 complex (TCR), Toll-like receptors (TLR) pathway,
      interferon (IFN) pathway, and antigen processing pathway. A total of 256 genes
      were analyzed across the four arrays. Genes that were significantly regulated
      between VRs and VNRs were CREB3L4, HIST1H3A, HIST1H3H, IFNA1, IFNA4, IFNA5,
      IFNA6, IFNA8, IFNA14, IFNG, IFNAR1, IL6, IRF9, MAPK4, MAPK5, MAPK14, NET1, and
      PIK3C2A in the IFN array. In the TCR array, HLA_B was found to be statistically
      significantly upregulated in both the VR and VNR groups; concomitantly, CD8A was
      found to be statistically significantly downregulated only in VRs. In the TLR
      array, only LBP and MAPK8 were found to be differentially regulated. In the
      antigen processing array, HLA-A, HLA-C, HLA-DMA, HLA-DMB, HLA-F, PSMA5, PSMB8,
      and PSMB9 were differentially downregulated. Based on these findings, it was
      determined that sinecatechins treatment modulates and downregulates genes
      involved in the pro-inflammatory response to HPV infection. 

PMID- 25774456
TI  - Decorated macrocycles via ring-closing double-reductive amination. identification
      of an apoptosis inducer of leukemic cells that at least partially antagonizes a 5
      HT2 receptor.
AB  - A build-couple-pair strategy, including double-reductive amination
      macrocyclization, has been used to generate decorated macrocycles (eannaphanes)
      with an embedded triazole and monosaccharide. Biological screening led to the
      identification of an inducer of apoptosis in leukemic cells, which acts at least
      partially as a 5-HT2 antagonist. 

PMID- 25774457
TI  - Adolescent Initiation of Cannabis Use and Early-Onset Psychosis.
AB  - BACKGROUND: It is important to evaluate the impact of cannabis use on onset and
      course of psychotic illness, as the increasing number of novice cannabis users
      may translate into a greater public health burden. This study aims to examine the
      relationship between adolescent onset of regular marijuana use and age of onset
      of prodromal symptoms, or first episode psychosis, and the manifestation of
      psychotic symptoms in those adolescents who use cannabis regularly. METHODS: A
      review was conducted of the current literature for youth who initiated cannabis
      use prior to the age of 18 and experienced psychotic symptoms at, or prior to,
      the age of 25. Seventeen studies met eligibility criteria and were included in
      this review. RESULTS: The current weight of evidence supports the hypothesis that
      early initiation of cannabis use increases the risk of early onset psychotic
      disorder, especially for those with a preexisting vulnerability and who have
      greater severity of use. There is also a dose-response association between
      cannabis use and symptoms, such that those who use more tend to experience
      greater number and severity of prodromal and diagnostic psychotic symptoms. Those
      with early-onset psychotic disorder and comorbid cannabis use show a poorer
      course of illness in regards to psychotic symptoms, treatment, and functional
      outcomes. However, those with early initiation of cannabis use appear to show a
      higher level of social functioning than non-cannabis users. CONCLUSIONS:
      Adolescent initiation of cannabis use is associated, in a dose-dependent fashion,
      with emergence and severity of psychotic symptoms and functional impairment such
      that those who initiate use earlier and use at higher frequencies demonstrate
      poorer illness and treatment outcomes. These associations appear more robust for
      adolescents at high risk for developing a psychotic disorder.

PMID- 25774458
TI  - Combination of dexamethasone and local anaesthetic solution in peripheral nerve
      blocks: A meta-analysis of randomised controlled trials.
AB  - BACKGROUND: Dexamethasone decreases postoperative pain and prolongs the duration
      of local anaesthetic peripheral nerve blocks in studies including a limited
      number of patients. OBJECTIVE: The objective of this study is to evaluate the
      effect of combining dexamethasone with local anaesthetic on sensory and motor
      peripheral nerve blockade in adults. DESIGN: A systematic review with meta
      analysis of randomised controlled trials. DATA SOURCES: We systematically
      searched in Medline, Embase, Google Scholar and Cochrane Controlled Trials
      Register up to December 2013. ELIGIBILITY CRITERIA: Randomised trials testing
      dexamethasone combined with local anaesthetic. RESULTS: Twelve trials (1054
      patients, 512 receiving perineural dexamethasone) were included. Ten studies
      evaluated dexamethasone for brachial plexus nerve block. Four to 10 mg
      dexamethasone-containing local anaesthetic solutions had a faster onset of action
      and resulted in a significant increase in the duration of analgesia [weighted
      mean difference (WMD) 351 min, 95% confidence interval (95% CI) 288 to 413, P <
      0.001] and motor blockade (WMD 277 min, 95% CI 167 to 387, P < 0.001) compared
      with local anaesthetic solutions alone. Time to onset of sensory and motor blocks
      was significantly reduced with dexamethasone (WMD -78 s, 95% CI -112 to -44, and 
      90 s, 95% CI -131 to -48, respectively). Dexamethasone significantly decreased
      postoperative nausea and vomiting (PONV, 9 vs. 27%, relative risk 0.36, 95% CI
      0.19 to 0.70). Subgroup analyses showed that dexamethasone approximately doubled
      the duration of postoperative analgesia when it was combined with intermediate
      acting (lidocaine, mepivacaine) or long-acting (bupivacaine, ropivacaine) local
      anaesthetics. CONCLUSION: Combining dexamethasone with local anaesthetics results
      in a prolongation of the duration of peripheral nerve block.

PMID- 25774459
TI  - Comparison of propofol pharmacokinetic and pharmacodynamic models for awake
      craniotomy: A prospective observational study.
AB  - BACKGROUND: Anaesthesia for awake craniotomy aims for an unconscious patient at
      the beginning and end of surgery but a rapidly awakening and responsive patient
      during the awake period. Therefore, an accurate pharmacokinetic/pharmacodynamic
      (PK/PD) model for propofol is required to tailor depth of anaesthesia. OBJECTIVE:
      To compare the predictive performances of the Marsh and the Schnider PK/PD models
      during awake craniotomy. DESIGN: A prospective observational study. SETTING:
      Single university hospital from February 2009 to May 2010. PATIENTS: Twelve
      patients undergoing elective awake craniotomy for resection of brain tumour or
      epileptogenic areas. INTERVENTION: Arterial blood samples were drawn at intervals
      and the propofol plasma concentration was determined. MAIN OUTCOME MEASURES: The
      prediction error, bias [median prediction error (MDPE)] and inaccuracy [median
      absolute prediction error (MDAPE)] of the Marsh and the Schnider models were
      calculated. The secondary endpoint was the prediction probability PK, by which
      changes in the propofol effect-site concentration (as derived from simultaneous
      PK/PD modelling) predicted changes in anaesthetic depth (measured by the
      bispectral index). RESULTS: The Marsh model was associated with a significantly
      (P = 0.05) higher inaccuracy (MDAPE 28.9 +/- 12.0%) than the Schnider model
      (MDAPE 21.5 +/- 7.7%) and tended to reach a higher bias (MDPE Marsh -11.7 +/-
      14.3%, MDPE Schnider -5.4 +/- 20.7%, P = 0.09). MDAPE was outside of accepted
      limits in six (Marsh model) and two (Schnider model) of 12 patients. The
      prediction probability was comparable between the Marsh (PK 0.798 +/- 0.056) and
      the Schnider model (PK 0.787 +/- 0.055), but after adjusting the models to each
      individual patient, the Schnider model achieved significantly higher prediction
      probabilities (PK 0.807 +/- 0.056, P = 0.05). CONCLUSION: When using the 'asleep
      awake-asleep' anaesthetic technique during awake craniotomy, we advocate using
      the PK/PD model proposed by Schnider. Due to considerable interindividual
      variation, additional monitoring of anaesthetic depth is recommended. TRIAL
      REGISTRATION: ClinicalTrials.gov identifier: NCT 01128465.

PMID- 25774460
TI  - Highly tunable molecular sieving and adsorption properties of mixed-linker
      zeolitic imidazolate frameworks.
AB  - Nanoporous zeolitic imidazolate frameworks (ZIFs) form structural topologies
      equivalent to zeolites. ZIFs containing only one type of imidazole linker show
      separation capability for limited molecular pairs. We show that the effective
      pore size, hydrophilicity, and organophilicity of ZIFs can be continuously and
      drastically tuned using mixed-linker ZIFs containing two types of linkers,
      allowing their use as a more general molecular separation platform. We illustrate
      this remarkable behavior by adsorption and diffusion measurements of
      hydrocarbons, alcohols, and water in mixed-linker ZIF-8(x)-90(100-x) materials
      with a large range of crystal sizes (338 nm to 120 MUm), using volumetric,
      gravimetric, and PFG-NMR methods. NMR, powder FT-Raman, and micro-Raman
      spectroscopy unambiguously confirm the mixed-linker nature of individual ZIF
      crystals. Variation of the mixed-linker composition parameter (x) allows
      continuous control of n-butane, i-butane, butanol, and isobutanol diffusivities
      over 2-3 orders of magnitude and control of water and alcohol adsorption
      especially at low activities.

PMID- 25774461
TI  - Misrepresenting the Accomplishments of Treatment.
AB  - The term "chronic relapsing disorder/disease" is viewed as an unfortunate
      shorthand expression that does an injustice to the accomplishments of treatment
      patients and treatment providers, and inadequately describes the findings from
      treatment evaluation research. Studies are reported that make clear relapse is
      not an inevitable consequence of substance abuse treatment, while substantial
      reductions in drug use and crime are routinely obtained consequent to treatment.
      It is past time to retire a term whose only virtue is brevity, and whose vices
      risk harm to a treatment population that is already stigmatized and a treatment
      system that is under frequent pressure. Thus, retiring this term provides the
      important benefit of recognizing the real achievements in behavior change
      obtained by treatment clients in conjunction with their service providers. 

PMID- 25774462
TI  - Honokiol downregulates Kruppel-like factor 4 expression, attenuates inflammation,
      and reduces histopathology after spinal cord injury in rats.
AB  - STUDY DESIGN: Randomized experimental study. OBJECTIVE: To investigate the
      neuroprotective effect of honokiol (HNK) on rats subjected to traumatic spinal
      cord injury (SCI) and the molecular mechanisms. SUMMARY OF BACKGROUND DATA:
      Inflammation contributes to the secondary injury to the spinal cord. Honokiol has
      been used as a neuroprotective agent because of its strong antioxidant and anti
      inflammatory properties. Kruppel-like factor 4 (Klf4) is a newly identified
      critical target for the anti-inflammatory effect of HNK. Whether HNK can inhibit
      inflammatory response in rat model of SCI through mediating the expression of
      Klf4 has yet to be elucidated. METHODS: Eighty-four adult female Sprague-Dawley
      rats were randomly divided into 4 groups as sham, SCI, SCI + Vehicle (0.1%
      propylene glycol in saline, intraperitoneally), and SCI + HNK (20 mg/kg,
      intraperitoneally) groups. The influences of HNK on the proinflammatory
      cytokines, microglial activation, neutrophil infiltration, histological changes,
      and improvement in motor function were assessed. RESULTS: In the SCI group,
      proinflammatory cytokines, microglial activation, neutrophil infiltration, and
      Klf4 expression levels were increased compared with the sham group (P < 0.001).
      HNK intervention downregulated the expression of Klf4, reduced the production of
      proinflammatory cytokines, inhibited microglial activation, and neutrophil
      infiltration (P < 0.05). Furthermore, HNK also reduced histopathology and
      improved functional outcome after traumatic SCI. CONCLUSION: HNK reduces
      secondary tissue damage and improves locomotor function recovery after SCI
      through suppressing inflammatory response, and can be used as a potential
      therapeutic agent for SCI. LEVEL OF EVIDENCE: NA.

PMID- 25774463
TI  - The minimum clinically important difference in SRS-22R total score, appearance,
      activity and pain domains after surgical treatment of adult spinal deformity.
AB  - STUDY DESIGN: Longitudinal cohort. OBJECTIVE: To establish minimum clinically
      important difference (MCID) threshold values for Scoliosis Research Society-22R
      (SRS-22R) domains in patients with adult spinal deformity undergoing surgical
      correction. SUMMARY OF BACKGROUND DATA: The SRS-22R has been shown to be
      reliable, valid and responsive to change in patients with adult spinal deformity
      undergoing surgery. The MCID quantifies a threshold of improvement that is
      clinically relevant to the patient. METHODS: Patients in a prospective database
      who completed the SRS-22R preoperatively and the SRS-30 1 year postoperatively
      were identified. Answers to the last 8 questions of the SRS-30 were used as
      anchors to determine MCID for the pain, appearance and activity domains,
      subscore, and total score using receiver-operating-characteristic curve analysis.
      Calculations of MCID using distribution-based methods were also done. RESULTS: A
      total of 1321 patients were included in the analysis; 83% were females and 10%
      were smokers. Mean age was 53 years. Mean body mass index was 26.3 kg/m. Mean
      preoperative SRS-22R appearance score was 2.50 improving to 3.62 at 1 year
      postoperatively (P < 0.001). Mean preoperative SRS-22R activity score was 2.96
      and it improved to 3.33 at 1 year postoperatively (P < 0.001). Mean preoperative
      SRS-22R pain score was 2.73 improving to 3.60 at 1 year postoperatively (P <
      0.001). Mean preoperative total score was 2.93 and it improved to 3.65 at 1 year
      postoperatively (P < 0.001). There was a statistically significant difference in
      domain scores among the responses to the anchors (P < 0.001). The different
      calculation methods yielded MCID values of 0.19 to 1.23 for appearance, 0.23 to
      0.60 for activity, 0.24 to 0.57 for pain, 0.16 to 0.43 for subscore, and 0.17 to
      0.71 for total score. CONCLUSION: When combined with previous reports, the
      results of this study in a population with adult spinal deformity undergoing
      surgical treatment show MCID for SRS-22 scores can be estimated as 0.4. This
      corresponds to a change of 1 interval in 2 of the 5 questions for a single
      domain. LEVEL OF EVIDENCE: 2.

PMID- 25774464
TI  - Clinical outcome in lumbar decompression surgery for spinal canal stenosis in the
      aged population: a prospective Swiss multicenter cohort study.
AB  - STUDY DESIGN: This is a prospective, multicenter cohort study including 8 medical
      centers in the metropolitan area of the Canton Zurich, Switzerland. OBJECTIVES:
      To examine whether outcome and quality of life might improve after decompression
      surgery for degenerative lumbar spinal stenosis (DLSS) even in patients older
      than 80 years and to compare data with a younger patient population from our own
      patient collective. SUMMARY AND BACKGROUND DATA: Lumbar decompression surgery
      without fusion has been shown to improve quality of life in lumbar spinal canal
      stenosis. In the population older than 80 years, treatment recommendations for
      DLSS show conflicting results. METHODS: Eight centers in the metropolitan area of
      Zurich, Switzerland agreed on the classification of DLSS, surgical principles,
      and follow-up protocols. Patients were followed from baseline, at 6 months, and
      12 months. Baseline characteristics were analyzed with 5 different questionnaires
      "Spinal Stenosis Measure, Feeling Thermometer, Numeric Rating Scale, 5D-3L, and
      Roland and Morris Disability Questionnaire." In addition, our study population
      was compared with a younger control group. Furthermore, we calculated the minimal
      clinically important differences. RESULTS: Thirty-seven patients with an average
      age of 82.5 +/- 2.5 years reached the 12-month follow-up. Spinal Stenosis Measure
      scores, the Feeling Thermometer, the Numeric Rating Scale, and the Roland and
      Morris Disability Questionnaire showed significant improvements at the 6-month
      and 12-month follow-ups (P < 0.001). One EQ-5D-3Lsubgroup "anxiety/depression"
      showed no significant improvement (P = 0.109) at 12-month follow-up. The minimal
      clinically important difference for the "Symptom Severity scale" in the Spinal
      Stenosis Measure was achieved with improvement of 70% in the older patient
      population. CONCLUSION: Patients 80 years or older can expect a clinically
      meaningful improvement after lumbar decompression for symptomatic DLSS. Our
      patient population showed significant positive development in quality of life in
      the short- and long-term follow-ups. LEVEL OF EVIDENCE: 3.

PMID- 25774465
TI  - Unplanned hospital readmission after surgical treatment of common lumbar
      pathologies: rates and causes.
AB  - STUDY DESIGN: Retrospective cohort study. OBJECTIVE: To assess the rate and
      causes of unplanned readmissions after surgical treatment of common degenerative
      lumbar pathologies within 90 days. SUMMARY OF BACKGROUND DATA: With pay-for
      performance and bundled payment compensation models being implemented; there is a
      growing emphasis to decrease the number of unplanned readmissions after surgery.
      Reports on degenerative lumbar spine pathology readmission rates are often
      obtained from national databases that lack clinical detail. Less published are
      the results from single-center institutions. METHODS: Hospital administrative
      database from a single-tertiary institution was queried to identify patients who
      underwent surgery for 6 common lumbar pathologies during a period from 2011 to
      2013. All readmissions within 90 days of discharge were reviewed for cause and
      rate of unplanned readmissions was calculated. RESULTS: A total of 1306 patients
      were identified who underwent surgery for various lumbar pathologies during a 2
      year time period. There were a total of 70 readmissions captured in the database
      that included 14 planned, 43 unplanned readmissions, and 13 coding errors. The
      unplanned readmission rate varied between 2.1% and 7.1% depending on pathology,
      with an overall rate of 3.3% within 90 days of discharge. Index length of stay,
      discharge disposition, severity of illness scores, and surgical approach were
      associated with readmission. The addition of fusion to decompression procedures
      did not seem to increase readmission rates. Surgical site infections and wound
      complications were the 2 most common reasons for readmissions accounting for 72%
      of all readmissions during the 90-day postdischarge period. CONCLUSION: The rate
      of readmission after surgery for common lumbar degenerative pathologies is
      relatively low. Surgical site infections and wound complications were the most
      common cause of readmission in this patient cohort. LEVEL OF EVIDENCE: 4.

PMID- 25774466
TI  - Lower thoracic pedicle morphometry: male, taller, and heavier specimens have
      bigger pedicles.
AB  - STUDY DESIGN: An anatomic study of pedicle dimensions was performed for lower
      thoracic vertebrae from American human subjects. OBJECTIVE: To quantify the
      dimensions of the lower thoracic pedicles and to better define the demographic
      factors that could ultimately govern the caliber selection of pedicle screws.
      SUMMARY OF BACKGROUND DATA: Transpedicular screw fixation allows for segmental
      instrumentation into multiple vertebrae across multilevel fusion area, offering
      considerable biomechanical advantage over the conventional hook and lateral mass
      fixation. Large variations in morphology from previous studies may be related to
      differences in demographics, sample size, and methodology. METHODS: For this
      study, T7-T12 vertebrae from 503 American human cadavers were directly measured
      with a digital caliper. Examiner measured each vertebra to determine medial
      lateral pedicle width and cranial-caudal pedicle height. Demographic information
      regarding age, sex, and race, as well as body height and weight, was available
      for all 503 subjects. RESULTS: Both pedicle height and pedicle width generally
      increased in size caudally down the lower thoracic spine. The highest pedicle
      height was at the T12 level with a mean of 17.08 mm. The widest pedicle width was
      at the T11 level with a mean of 9.31 mm. Males have larger pedicles than females
      for all upper thoracic levels. The tallest and heaviest groups had larger
      pedicles than the shorter and lighter groups, respectively. Age and race did not
      consistently affect pedicle dimension in a statistically significant manner.
      CONCLUSION: Our large-scale study of American specimens characterized the
      relationship between pedicle dimensions and a variety of demographic factors such
      as age, sex, body height and weight. With substantial statistical power, this
      study showed that male, taller, and heavier individuals had larger pedicles.
      LEVEL OF EVIDENCE: N/A.

PMID- 25774467
TI  - Clinical significance of achieving a flexion limitation with a tension band
      system in grade 1 degenerative spondylolisthesis: a minimum 5-year follow-up.
AB  - STUDY DESIGN: Retrospective clinical study. OBJECTIVE: To evaluate the effect of
      the limitation of flexion rotation clinically and radiologically after
      interspinous soft stabilization using a tension band system in grade 1
      degenerative spondylolisthesis. SUMMARY OF BACKGROUND DATA: Although several
      studies have been published on the clinical effects of limiting rotatory motion
      using tension band systems, which mainly targets the limitation of flexion rather
      than that of extension, they were confined to the category of pedicle screw-based
      systems, revealing inconsistent long-term outcomes. METHODS: Sixty-one patients
      with a mean age of 60.6 years (range, 28-76 yr) who underwent interspinous soft
      stabilization after decompression for grade 1 degenerative spondylolisthesis with
      stenosis between 2002 and 2004 were analyzed. At follow-up, the patients were
      divided into 2 groups on the basis of their achievement or failure to achieve
      flexion limitation. The clinical and radiological findings were analyzed. A
      multiple linear regression analysis was performed to determine the prognostic
      factors for surgical outcomes. RESULTS: At a mean follow-up duration of 72.5
      months (range, 61-82 mo), 51 patients were classified into the flexion-limited
      group and 10 into the flexion-unlimited group. Statistically significant
      improvements were noted only in the flexion-limited group in all clinical scores.
      In the flexion-unlimited group, there were significant deteriorations in flexion
      angle (P = 0.009), axial thickness of the ligamentum flavum (P = 0.013), and the
      foraminal cross-sectional area (P = 0.011), resulting in significant intergroup
      differences. The preoperative extension angle was identified as the most
      influential variable for the flexion limitation and the clinical outcomes.
      CONCLUSION: The effects of the limitation of flexion rotation achieved through
      interspinous soft stabilization using a tension band system after decompression
      were related to the prevention of late recurrent stenosis and resultant radicular
      pain caused by flexion instability. The extension potential at the index level
      was recognized as a major prognostic factor that can predict the flexion
      limitation and the clinical results. LEVEL OF EVIDENCE: 4.

PMID- 25774468
TI  - Item response theory analysis of the modified Roland-Morris Disability
      Questionnaire in a population-based study.
AB  - STUDY DESIGN: This is a secondary analysis of a cross-sectional population-based
      survey. OBJECTIVE: Shorten the modified 23-item Roland (mRoland) scale using item
      response theory (IRT) methods and describe where in the functional disability
      range each scale is the most precise. SUMMARY OF BACKGROUND DATA: The Roland
      Morris Disability Questionnaire is recommended for a functional disability
      outcome measure in patients with low back pain (LBP). One commonly used version
      is the Roland. It is unknown where in the functional disability range the Roland
      measures. METHODS: One candidate individual with LBP in randomly selected
      households was interviewed, identifying 694 adults with chronic LBP. To justify
      the use of a unidimensional 2-parameter logistic IRT model, we performed both
      exploratory and confirmatory factor analysis. RESULTS: Exploratory factor
      analysis revealed one dominant eigenvalue. Confirmatory factor analysis results
      indicate that the 1-factor model fit well. IRT analysis revealed variability in
      the slopes, in the range from 1.07 to 3.10. The marginal reliability, an IRT
      based analog to coefficient alpha, was 0.88. The mRoland produces reliable scores
      (i.e., with a standard error <0.3) from 1.4 standard deviations below the mean to
      roughly 0.2 above the mean. CONCLUSION: The mRoland measures one construct. The
      mRoland seems to be an excellent tool for measuring just-below-average levels of
      functional disability. The mRoland measures high levels of functional disability
      with relatively poor reliability and may be more appropriate for a less-disabled
      population with LBP. We demonstrate that the mRoland can be shortened to 11 items
      with minimal loss of information. We show that there are different ways to go
      about selecting the set of 11 items that yield short forms with different
      strengths. LEVEL OF EVIDENCE: 3.

PMID- 25774469
TI  - Guillain-Barre syndrome after pelvic fracture fixation: a rare cause of
      postoperative paralysis.
AB  - STUDY DESIGN: Case report. OBJECTIVE: To describe the important epidemiology,
      clinical presentation, and pathophysiology of Guillain-Barre syndrome (GBS) after
      orthopedic surgery in a trauma patient. SUMMARY OF BACKGROUND DATA: Little in the
      orthopedic literature describes trauma as an etiology of GBS. We report a case of
      post-traumatic GBS in a 52-year-old male who developed ascending weakness after
      experiencing pelvic trauma that required 2 separate orthopedic procedures for
      pelvic stabilization after a fall from a height of 12 ft. After the index
      operative procedure, the patient complained of left S1 numbness. Computed
      tomographic scan demonstrated the pelvic screw approximating the left S1
      neuroforamen and correlated with the patient's immediate postoperative symptoms.
      A secondary procedure to reposition the screw alleviated the patient's left S1
      numbness. Two weeks postoperatively, the patient developed profound ascending
      lower extremity weakness. This case highlights the importance of considering all
      etiologies, no matter how uncommon, in the differential diagnosis of lower
      extremity weakness. METHODS: Case report with literature search on GBS in
      orthopedic trauma patient. RESULTS: We propose that direct neural trauma from
      poorly positioned hardware resulting in clinical neurological symptoms may have
      been the inciting event that caused GBS in this trauma patient. CONCLUSION: Post
      traumatic GBS is a rare, potentially life-threatening cause of weakness. Once
      mechanical causes are ruled out with appropriate imaging, all etiologies in the
      differential diagnosis must be explored. If the image findings cannot explain the
      clinical examination, other biologic causes of weakness, including GBS, must be
      explored. The causes of GBS in the postoperative trauma patient include
      infection, trauma, surgery, or direct neural injury. LEVEL OF EVIDENCE: 4.

PMID- 25774471
TI  - Subcutaneous and total fat at L4-L5 and subcutaneous, visceral and total fat at
      L3-L4 are important contributors of fasting and postprandial adiponectin levels.
AB  - OBJECTIVES: Insulin resistance and central obesity have been implicated in the
      pathogenesis of hypoadiponectinemia in obesity. The aim of this study is to
      evaluate circulating post-prandial adiponectin in relation to glucose and insulin
      metabolism, indexes of insulin resistance and sensitivity and, indexes of body
      fat accumulation and distribution in obese men. METHODS: Twenty-eight non
      diabetic men underwent an OGTT followed by an oral fat load and were studied at
      baseline and for 5 h post-prandially for serum adiponectin, glucose and insulin.
      Insulin resistance was estimated by Homeostasis model assessment (HOMA) and
      insulin sensitivity by Matsuda index. Body fat accumulation and distribution were
      evaluated by anthropometric indexes and multiple slices MRI of the abdomen and
      hip. RESULTS: Adiponectin was negatively correlated to insulin levels. Fasting
      and area under the curve (AUC) adiponectin levels were negatively correlated to
      HOMA (both p < 0.01) and positively to Matsuda index (both p < 0.05). Negative
      correlations between fasting adiponectin and total fat (r = -0.408, p < 0.05),
      AUC adiponectin and subcutaneous, visceral and total fat (r = -0.375, -0.413 and 
      0.475 respectively, all p < 0.05) at L3-L4 were found, and negative correlations
      between fasting adiponectin and subcutaneous (r = -0.402, p < 0.05) and total fat
      (r = -0.491, p < 0.05) and between AUC adiponectin and subcutaneous and total fat
      (r = -0.506 and -0.547, respectively, both p < 0.01) were present at L4-L5.
      CONCLUSIONS: Circulating adiponectin is inversely correlated to both visceral and
      subcutaneous fat in non-diabetic men, implying that both compartments are
      important for adiponectin levels. The best correlation is found at measurement
      site L4-L5.

PMID- 25774474
TI  - An overview of the Kidney Cancer Association.

PMID- 25774472
TI  - Photoluminescence of oxygen vacancies and hydroxyl group surface functionalized
      SnO2 nanoparticles.
AB  - We report, for the first time, the luminescence property of the hydroxyl group
      surface functionalized quantum dots (QDs) and nanoparticles (NPs) of SnO2 using
      low energy excitations of 2.54 eV (488 nm) and 2.42 eV (514.5 nm). This
      luminescence is in addition to generally observed luminescence from 'O' defects.
      The as-prepared SnO2 QDs are annealed at different temperatures under ambient
      conditions to create NPs with varying sizes. Subsequently, the average size of
      the NPs is calculated from the acoustic vibrations observed at low frequencies in
      the Raman spectra and by the transmission electron microscopy measurements.
      Detailed photoluminescence studies with 3.815 eV (325 nm) excitation reveal the
      nature of in-plane and bridging 'O' vacancies as well as adsorption and
      desorption occurring at different annealing temperatures. X-ray photoelectron
      spectroscopy studies also support this observation. The defect level related to
      the surface -OH functional groups shows a broad luminescence peak at around 1.96
      eV in SnO2 NPs which is elaborated using temperature dependent studies. 

PMID- 25774475
TI  - The use of granulocyte-macrophage colony-stimulating factor in melanoma
      treatment.

PMID- 25774476
TI  - Redefining dose-limiting toxicity.

PMID- 25774477
TI  - Bevacizumab vs EGFR antibodies in metastatic colorectal cancer.

PMID- 25774478
TI  - Evolving treatments in acute myeloid leukemia.

PMID- 25774480
TI  - Long-term toxicity of chemotherapy and radiotherapy in lymphoma survivors:
      optimizing treatment for individual patients.
AB  - Lymphoma treatment has evolved to reflect the fact that even when cure is
      achieved, significant chronic or late-onset toxicity can vitiate long-term
      patient outcomes. Previously, the sole focus of treatment was on maximizing cure
      rates. Now, the emphasis is on titrating treatment intensity to retain or improve
      cure rates while limiting treatment-associated late effects. To accomplish this
      on an individual basis remains clinically challenging. Most of the agents used in
      the treatment of Hodgkin and non-Hodgkin lymphoma have the potential to produce
      late--manifesting toxicities such as cardiac dysfunction, second malignancy, and
      infertility. This review outlines some of the evidence regarding late effects of
      chemotherapy and radiation for lymphoma, with emphasis on how understanding
      individual patient characteristics can affect the potential late toxicity of
      different treatment options.

PMID- 25774481
TI  - Advances in the diagnosis and treatment of childhood and adolescent B-cell non
      Hodgkin lymphoma.
AB  - Burkitt lymphoma and diffuse large B-cell lymphoma represent the majority of
      mature B-cell non-Hodgkin lymphomas in children, adolescents, and young adults.
      Although they are characterized by specific clinical and biological nuances, the
      2 diseases share significant clinicopathologic overlap and are treated with the
      same chemotherapy regimens in pediatrics. Modern-day chemotherapy protocols
      achieve overall event-free survival rates of nearly 90%. The addition of the anti
      CD20 monoclonal antibody rituximab to backbone chemotherapy holds great promise
      for improving long-term curative outcomes while diminishing acute and long-term
      toxicities. However, in the contemporary era, the long-term survival for patients
      with relapsed or refractory disease is meager. The role of hematopoietic stem
      cell transplantation in children, adolescents, and young adults with
      relapsed/refractory disease is currently being defined. Meanwhile, novel humoral
      and cellular immunotherapies, as well as agents targeting specific molecular
      pathways that drive lymphomagenesis, are exciting developments that are being
      evaluated in clinical trials. 

PMID- 25774482
TI  - Selecting early therapy in prostate cancer.

PMID- 25774483
TI  - A Perspective on Cigarette Smoking During Alcohol and Substance Use Treatment.
AB  - Individuals in treatment for substance use continue to smoke at higher rates than
      the general population of the United States. This editorial presents a different
      perspective on cigarette smoking that might reflect aspects of the subculture of
      individuals who, representing a heterogeneous population, smoke while recovering
      from substance use associated problems. We discuss factors that independently
      and, in combination, influence cigarette smoking during treatment and recovery
      from substance use. We conclude that more qualitative research is needed to
      understand which factors, not typically emphasized in standard tobacco cessation
      programming, may contribute to cigarette smoking cessation for this population. 

PMID- 25774485
TI  - Valuing our patients' preferences.

PMID- 25774487
TI  - Development and validation of a risk-prediction algorithm for the recurrence of
      panic disorder.
AB  - BACKGROUND: To develop and validate a risk prediction algorithm for the
      recurrence of panic disorder. METHODS: Three-year longitudinal data were taken
      from the National Epidemiologic Survey on Alcohol and Related Conditions
      (2001/2002-2004/2005). One thousand six hundred and eighty one participants with
      a lifetime panic disorder and who had not had panic attacks for at least 2 months
      at baseline were included. The development cohort included 949 participants; 732
      from different census regions were in the validation cohort. Recurrence of panic
      disorder over the follow-up period was assessed using the Alcohol Use Disorder
      and Associated Disabilities Interview Schedule, based on the DSM-IV criteria.
      Logistic regression was used for deriving the algorithm. Discrimination and
      calibration were assessed in the development and the validation cohorts. RESULTS:
      The developed algorithm consisted of 11 predictors: age, sex, panic disorder in
      the past 12 months, nicotine dependence, rapid heartbeat/tachycardia, taking
      medication for panic attacks, feelings of choking and persistent worry about
      having another panic attack, two personality traits, and childhood trauma. The
      algorithm had good discriminative power (C statistic = 0.7863, 95% CI: 0.7487,
      0.8240). The C statistic was 0.7283 (95% CI: 0.6889, 0.7764) in the external
      validation data set. CONCLUSIONS: The developed risk algorithm for predicting the
      recurrence of panic disorder has good discrimination and excellent calibration.
      Data related to the predictors can be easily attainable in routine clinical
      practice. It can be used by clinicians to calculate the probability of recurrence
      of panic disorder in the next 3 years for individual patients, communicate with
      patients regarding personal risks, and thus improve personalized treatment
      approaches.

PMID- 25774486
TI  - Oriented cell division shapes carnivorous pitcher leaves of Sarracenia purpurea.
AB  - Complex morphology is an evolutionary outcome of phenotypic diversification. In
      some carnivorous plants, the ancestral planar leaf has been modified to form a
      pitcher shape. However, how leaf development was altered during evolution remains
      unknown. Here we show that the pitcher leaves of Sarracenia purpurea develop
      through cell division patterns of adaxial tissues that are distinct from those in
      bifacial and peltate leaves, subsequent to standard expression of adaxial and
      abaxial marker genes. Differences in the orientation of cell divisions in the
      adaxial domain cause bifacial growth in the distal region and adaxial ridge
      protrusion in the middle region. These different growth patterns establish
      pitcher morphology. A computer simulation suggests that the cell division plane
      is critical for the pitcher morphogenesis. Our results imply that tissue-specific
      changes in the orientation of cell division underlie the development of a
      morphologically complex leaf. 

PMID- 25774488
TI  - Sigma- versus pi-activation of alkynyl benzoates using B(C6F5)3.
AB  - We have prepared a range of alkynyl benzoates in high yields and have
      investigated their reactivities with the strong Lewis acid B(C6F5)3. In such
      molecules both sigma-activation of the carbonyl and pi-activation of the alkyne
      are possible. In contrast to the reactivity of propargyl esters with B(C6F5)3
      which proceed via 1,2-addition of the ester and B(C6F5)3 across the alkyne, the
      inclusion of an additional CH2 spacer switches off the intramolecular cyclization
      and selective sigma-activation of the carbonyl group is observed through adduct
      formation. This change in reactivity appears due to the instability of the
      species which would be formed through B(C6F5)3 activation of the alkyne. 

PMID- 25774489
TI  - Anti-ageing effects of Sonchus oleraceus L. (puha) leaf extracts on H2O2-induced
      cell senescence.
AB  - Antioxidants protect against damage from free radicals and are believed to slow
      the ageing process. Previously, we have reported the high antioxidant activity of
      70% methanolic Sonchus oleraceus L. (Asteraceae) leaf extracts. We hypothesize
      that S. oleraceus extracts protect cells against H2O2-induced senescence by
      mediating oxidative stress. Premature senescence of young WI-38 cells was induced
      by application of H2O2. Cells were treated with S. oleraceus extracts before or
      after H2O2 stress. The senescence- associated beta-galactosidase (SA-beta-gal)
      activity was used to indicate cell senescence. S. oleraceus extracts showed
      higher cellular antioxidant activity than chlorogenic acid in WI-38 cells. S.
      oleraceus extracts suppressed H2O2 stress-induced premature senescence in a
      concentration-dependent manner. At 5 and 20 mg/mL, S. oleraceus extracts showed
      better or equivalent effects of reducing stress-induced premature senescence than
      the corresponding ascorbic acid treatments. These findings indicate the potential
      of S. oleraceus extracts to be formulated as an anti-ageing agent.

PMID- 25774491
TI  - Ni-SiO2 catalysts for the carbon dioxide reforming of methane: varying support
      properties by flame spray pyrolysis.
AB  - Silica particles were prepared by flame spray pyrolysis (FSP) as a support for
      nickel catalysts. The impact of precursor feed rate (3, 5 and 7 mL/min) during
      FSP on the silica characteristics and the ensuing effect on catalytic performance
      for the carbon dioxide, or dry, reforming of methane (DRM) was probed. Increasing
      the precursor feed rate: (i) progressively lowered the silica surface area from
      ~340 m2/g to ~240 m2/g; (ii) altered the silanol groups on the silica surface;
      and (iii) introduced residual carbon-based surface species to the sample at the
      highest feed rate. The variations in silica properties altered the (5 wt %)
      nickel deposit characteristics which in turn impacted on the DRM reaction. As the
      silica surface area increased, the nickel dispersion increased which improved
      catalyst performance. The residual carbon-based species also appeared to improve
      nickel dispersion, and in turn catalyst activity, although not to the same extent
      as the change in silica surface area. The findings illustrate both the importance
      of silica support characteristics on the catalytic performance of nickel for the
      DRM reaction and the capacity for using FSP to control these characteristics.

PMID- 25774490
TI  - Multifaceted strategy for the synthesis of diverse 2,2'-bithiophene derivatives.
AB  - New catalytically or high pressure activated reactions and routes, including
      coupling, double bond migration in allylic systems, and various types of
      cycloaddition and dihydroamination have been used for the synthesis of novel
      bithiophene derivatives. Thanks to the abovementioned reactions and routes
      combined with non-catalytic ones, new acetylene, butadiyne, isoxazole, 1,2,3
      triazole, pyrrole, benzene, and fluoranthene derivatives with one, two or six
      bithiophenyl moieties have been obtained. Basic sources of crucial substrates
      which include bithiophene motif for catalytic reactions were 2,2'-bithiophene,
      gaseous acetylene and 1,3-butadiyne.

PMID- 25774493
TI  - Construction of an isonucleoside on a 2,6-dioxobicyclo[3.2.0]-heptane skeleton.
AB  - We have built a new isonucleoside derivative on a 2,6-dioxobicyclo[3.2.0]heptane
      skeleton as a potential anti-HIV agent. To synthesize the target compound, an
      acetal-protected dihydroxyacetone was first converted to a 2,3-epoxy
      tetrahydrofuran derivative. Introduction of an azide group, followed by the
      formation of an oxetane ring, gave a pseudosugar derivative with a 2,6
      dioxobicyclo[3.2.0]heptane skeleton. The desired isonucleoside was obtained by
      constructing a purine base moiety on the scaffold, followed by amination.

PMID- 25774492
TI  - Targeting N-glycan cryptic sugar moieties for broad-spectrum virus
      neutralization: progress in identifying conserved molecular targets in viruses of
      distinct phylogenetic origins.
AB  - Identifying molecular targets for eliciting broadly virus-neutralizing antibodies
      is one of the key steps toward development of vaccines against emerging viral
      pathogens. Owing to genomic and somatic diversities among viral species,
      identifying protein targets for broad-spectrum virus neutralization is highly
      challenging even for the same virus, such as HIV-1. However, viruses rely on host
      glycosylation machineries to synthesize and express glycans and, thereby, may
      display common carbohydrate moieties. Thus, exploring glycan-binding profiles of
      broad-spectrum virus-neutralizing agents may provide key information to uncover
      the carbohydrate-based virus-neutralizing epitopes. In this study, we
      characterized two broadly HIV-neutralizing agents, human monoclonal antibody 2G12
      and Galanthus nivalis lectin (GNA), for their viral targeting activities.
      Although these agents were known to be specific for oligomannosyl antigens, they
      differ strikingly in virus-binding activities. The former is HIV-1 specific; the
      latter is broadly reactive and is able to neutralize viruses of distinct
      phylogenetic origins, such as HIV-1, severe acute respiratory syndrome
      coronavirus (SARS-CoV), and human cytomegalovirus (HCMV). In carbohydrate
      microarray analyses, we explored the molecular basis underlying the striking
      differences in the spectrum of anti-virus activities of the two probes. Unlike
      2G12, which is strictly specific for the high-density Man9GlcNAc2Asn (Man9)
      clusters, GNA recognizes a number of N-glycan cryptic sugar moieties. These
      include not only the known oligomannosyl antigens but also previously
      unrecognized tri-antennary or multi-valent GlcNAc-terminating N-glycan epitopes
      (Tri/m-Gn). These findings highlight the potential of N-glycan cryptic sugar
      moieties as conserved targets for broad-spectrum virus neutralization and suggest
      the GNA-model of glycan-binding warrants focused investigation. 

PMID- 25774494
TI  - Successful bone marrow transplantation of an adolescent young adult female with
      pregnancy-associated aplastic anemia.
AB  - Cases of pregnancy-associated severe aplastic anemia (SAA) have been reported in
      the literature with historically high rates of mortality. We report the case of a
      17-year-old female diagnosed with SAA at 26 weeks of gestation. She experienced
      intrauterine fetal demise and did not achieve hematologic remission after
      delivery. She received a histocompatible sibling donor bone marrow transplant 7
      weeks after her diagnosis and remains in remission, at 1-year posttransplant. We
      review available literature and suggest that when a histocompatible sibling donor
      is available, bone marrow transplantation should be considered as a first-line
      therapy for patients with pregnancy-associated SAA. 

PMID- 25774495
TI  - Probing the morphological influence on solid electrolyte interphase and impedance
      response in intercalation electrodes.
AB  - Solid electrolyte interphase (SEI) formation, due to the electrochemical reaction
      between the salt and solvent in the electrolyte, is a key contributor to the
      electrode performance decay in lithium-ion batteries. The active particle
      morphology and electrode microstructure affect the side reaction rate and hence
      the SEI induced interfacial transport and impedance behavior. The change
      resistance due to the variation of SEI thickness can be inferred from
      electrochemical impedance spectroscopy. In this study, we proposed a
      microstructure-aware impedance model to predict the effect of electrode
      microstructure on impedance response. Our model successfully captures the
      influence of active particle morphology on the SEI formation and corresponding
      impedance characteristics. Different electrode realizations with microstructural
      and compositional variations have been considered. The critical influence of
      active material morphology, mean particle size, binder and electrolyte volume
      fractions on the SEI formation and impedance behavior reveals the underlying
      interdependences of the interfacial and transport resistance modes. 

PMID- 25774496
TI  - Endogenous prostaglandins and afferent sensory nerves in gastroprotective effect
      of hydrogen sulfide against stress-induced gastric lesions.
AB  - Hydrogen sulfide (H2S) plays an important role in human physiology, exerting
      vasodilatory, neuromodulatory and anti-inflammatory effects. H2S has been
      implicated in the mechanism of gastrointestinal integrity but whether this
      gaseous mediator can affect hemorrhagic lesions induced by stress has been little
      elucidated. We studied the effect of the H2S precursor L-cysteine, H2S-donor
      NaHS, the H2S synthesizing enzyme (CSE) activity inhibitor- D,L-propargylglycine
      (PAG) and the gastric H2S production by CSE/CBS/3-MST activity in water immersion
      and restraint stress (WRS) ulcerogenesis and the accompanying changes in gastric
      blood flow (GBF). The role of endogenous prostaglandins (PGs) and sensory
      afferent nerves releasing calcitonin gene-related peptide (CGRP) in the mechanism
      of gastroprotection induced by H2S was examined in capsaicin-denervated rats and
      those pretreated with capsazepine to inhibit activity of vanilloid receptors (VR
      1). Rats were pretreated with vehicle, NaHS, the donor of H2S and or L-cysteine,
      the H2S precursor, with or without the concurrent treatment with 1) nonselective
      (indomethacin) and selective cyclooxygenase (COX)-1 (SC-560) or COX-2 (rofecoxib)
      inhibitors. The expression of mRNA and protein for COX-1 and COX-2 were analyzed
      in gastric mucosa pretreated with NaHS with or without PAG. Both NaHS and L
      cysteine dose-dependently attenuated severity of WRS-induced gastric lesions and
      significantly increased GBF. These effects were significantly reduced by
      pretreatment with PAG and capsaicin denervation. NaHS increased gastric H2S
      production via CSE/CBS but not 3-MST activity. Inhibition of COX-1 and COX-2
      activity significantly diminished NaHS- and L-cysteine-induced protection and
      hyperemia. NaHS increased expression of COX-1, COX-2 mRNAs and proteins and
      raised CGRP mRNA expression. These effects of NaHS on COX-1 and COX-2 protein
      contents were reversed by PAG and capsaicin denervation. We conclude that H2S
      exerts gastroprotection against WRS-induced gastric lesions by the mechanism
      involving enhancement in gastric microcirculation mediated by endogenous PGs,
      sensory afferent nerves releasing CGRP and the activation of VR-1 receptors. 

PMID- 25774497
TI  - Increased perfusion in normal appearing white matter in high inflammatory
      multiple sclerosis patients.
AB  - PURPOSE: Although cerebral perfusion alterations have long been acknowledged in
      multiple sclerosis (MS), the relationship between measurable perfusion changes
      and the status of highly active MS has not been examined. We hypothesized that
      alteration of perfusion can be detected in normal appearing white matter and is
      increased in high inflammatory patients. MATERIALS AND METHODS: Thirty-three
      patients with relapsing-remitting MS underwent four monthly 3T MRI scans
      including dynamic susceptibility contrast perfusion-weighted MRI. Cerebral blood
      flow (CBF) and cerebral blood volume (CBV) were measured in normal appearing
      white matter. Patients were stratified in a high- and low-inflammatory group
      according to the number of new contrast enhancing lesions. RESULTS: Thirteen
      patients were classified as high-inflammatory. Compared to low-inflammatory
      patients, the high-inflammatory group demonstrated significantly higher CBV (p =
      0.001) and CBF (p = 0.014) values. A mixed model analysis to assess independent
      variables associated with CBV and CBF revealed that white matter lesion load and
      atrophy measurements had no significant influence on CBF and CBV. CONCLUSION:
      This work provides evidence that high inflammatory lesion load is associated with
      increased CBV and CBF, underlining the role of global modified microcirculation
      prior to leakage of the blood-brain barrier in the pathophysiology of MS.
      Perfusion changes might therefore be sensitive to active inflammation apart from
      lesion development without local blood-brain barrier breakdown, and could be
      utilized to further assess the metabolic aspect of current inflammation.

PMID- 25774498
TI  - Microbial forensics: predicting phenotypic characteristics and environmental
      conditions from large-scale gene expression profiles.
AB  - A tantalizing question in cellular physiology is whether the cellular state and
      environmental conditions can be inferred by the expression signature of an
      organism. To investigate this relationship, we created an extensive normalized
      gene expression compendium for the bacterium Escherichia coli that was further
      enriched with meta-information through an iterative learning procedure. We then
      constructed an ensemble method to predict environmental and cellular state,
      including strain, growth phase, medium, oxygen level, antibiotic and carbon
      source presence. Results show that gene expression is an excellent predictor of
      environmental structure, with multi-class ensemble models achieving balanced
      accuracy between 70.0% (+/-3.5%) to 98.3% (+/-2.3%) for the various
      characteristics. Interestingly, this performance can be significantly boosted
      when environmental and strain characteristics are simultaneously considered, as a
      composite classifier that captures the inter-dependencies of three
      characteristics (medium, phase and strain) achieved 10.6% (+/-1.0%) higher
      performance than any individual models. Contrary to expectations, only 59% of the
      top informative genes were also identified as differentially expressed under the
      respective conditions. Functional analysis of the respective genetic signatures
      implicates a wide spectrum of Gene Ontology terms and KEGG pathways with
      condition-specific information content, including iron transport, transferases,
      and enterobactin synthesis. Further experimental phenotypic-to-genotypic mapping
      that we conducted for knock-out mutants argues for the information content of top
      ranked genes. This work demonstrates the degree at which genome-scale
      transcriptional information can be predictive of latent, heterogeneous and
      seemingly disparate phenotypic and environmental characteristics, with far
      reaching applications. 

PMID- 25774499
TI  - Frequent somatic reversion of KRT1 mutations in ichthyosis with confetti.
AB  - Widespread reversion of genetic disease is rare; however, such events are
      particularly evident in some skin disorders in which normal clones develop on a
      background of affected skin. We previously demonstrated that mutations in keratin
      10 (KRT10) cause ichthyosis with confetti (IWC), a severe dominant disorder that
      is characterized by progressive development of hundreds of normal skin spots via
      revertant mosaicism. Here, we report on a clinical and histological IWC subtype
      in which affected subjects have red, scaly skin at birth, experience worsening
      palmoplantar keratoderma in childhood, and develop hundreds of normal skin spots,
      beginning at around 20 years of age, that increase in size and number over time.
      We identified a causal de novo mutation in keratin 1 (KRT1). Similar to IWC
      causing KRT10 mutations, this mutation in KRT1 resulted in a C-terminal
      frameshift, replacing 22 C-terminal amino acids with an alternate 30-residue
      peptide. Mutant KRT1 caused partial collapse of the cytoplasmic intermediate
      filament network and mislocalized to the nucleus. As with KRT10 mutations causing
      IWC, reversion of KRT1 mutations occurred via mitotic recombination. Because
      reversion is not observed with other disease-causing keratin mutations, the
      results of this study implicate KRT1 and KRT10 C-terminal frameshift mutations in
      the high frequency of revertant mosaicism in IWC. 

PMID- 25774500
TI  - Severe myopathy in mice lacking the MEF2/SRF-dependent gene leiomodin-3.
AB  - Maintenance of skeletal muscle structure and function requires a precise
      stoichiometry of sarcomeric proteins for proper assembly of the contractile
      apparatus. Absence of components of the sarcomeric thin filaments causes nemaline
      myopathy, a lethal congenital muscle disorder associated with aberrant myofiber
      structure and contractility. Previously, we reported that deficiency of the kelch
      like family member 40 (KLHL40) in mice results in nemaline myopathy and
      destabilization of leiomodin-3 (LMOD3). LMOD3 belongs to a family of tropomodulin
      related proteins that promote actin nucleation. Here, we show that deficiency of
      LMOD3 in mice causes nemaline myopathy. In skeletal muscle, transcription of
      Lmod3 was controlled by the transcription factors SRF and MEF2. Myocardin-related
      transcription factors (MRTFs), which function as SRF coactivators, serve as
      sensors of actin polymerization and are sequestered in the cytoplasm by actin
      monomers. Conversely, conditions that favor actin polymerization de-repress MRTFs
      and activate SRF-dependent genes. We demonstrated that the actin nucleator LMOD3,
      together with its stabilizing partner KLHL40, enhances MRTF-SRF activity. In
      turn, SRF cooperated with MEF2 to sustain the expression of LMOD3 and other
      components of the contractile apparatus, thereby establishing a regulatory
      circuit to maintain skeletal muscle function. These findings provide insight into
      the molecular basis of the sarcomere assembly and muscle dysfunction associated
      with nemaline myopathy. 

PMID- 25774501
TI  - Progesterone and HMOX-1 promote fetal growth by CD8+ T cell modulation.
AB  - Intrauterine growth restriction (IUGR) affects up to 10% of pregnancies in
      Western societies. IUGR is a strong predictor of reduced short-term neonatal
      survival and impairs long-term health in children. Placental insufficiency is
      often associated with IUGR; however, the molecular mechanisms involved in the
      pathogenesis of placental insufficiency and IUGR are largely unknown. Here, we
      developed a mouse model of fetal-growth restriction and placental insufficiency
      that is induced by a midgestational stress challenge. Compared with control
      animals, pregnant dams subjected to gestational stress exhibited reduced
      progesterone levels and placental heme oxygenase 1 (Hmox1) expression and
      increased methylation at distinct regions of the placental Hmox1 promoter. These
      stress-triggered changes were accompanied by an altered CD8+ T cell response, as
      evidenced by a reduction of tolerogenic CD8+CD122+ T cells and an increase of
      cytotoxic CD8+ T cells. Using progesterone receptor- or Hmox1-deficient mice, we
      identified progesterone as an upstream modulator of placental Hmox1 expression.
      Supplementation of progesterone or depletion of CD8+ T cells revealed that
      progesterone suppresses CD8+ T cell cytotoxicity, whereas the generation of
      CD8+CD122+ T cells is supported by Hmox1 and ameliorates fetal-growth restriction
      in Hmox1 deficiency. These observations in mice could promote the identification
      of pregnancies at risk for IUGR and the generation of clinical interventional
      strategies. 

PMID- 25774502
TI  - Tumor cell migration screen identifies SRPK1 as breast cancer metastasis
      determinant.
AB  - Tumor cell migration is a key process for cancer cell dissemination and
      metastasis that is controlled by signal-mediated cytoskeletal and cell matrix
      adhesion remodeling. Using a phagokinetic track assay with migratory H1299 cells,
      we performed an siRNA screen of almost 1,500 genes encoding kinases/phosphatases
      and adhesome- and migration-related proteins to identify genes that affect tumor
      cell migration speed and persistence. Thirty candidate genes that altered cell
      migration were validated in live tumor cell migration assays. Eight were
      associated with metastasis-free survival in breast cancer patients, with integrin
      beta3-binding protein (ITGB3BP), MAP3K8, NIMA-related kinase (NEK2), and SHC
      transforming protein 1 (SHC1) being the most predictive. Examination of genes
      that modulate migration indicated that SRPK1, encoding the splicing factor kinase
      SRSF protein kinase 1, is relevant to breast cancer outcomes, as it was highly
      expressed in basal breast cancer. Furthermore, high SRPK1 expression correlated
      with poor breast cancer disease outcome and preferential metastasis to the lungs
      and brain. In 2 independent murine models of breast tumor metastasis, stable
      shRNA-based SRPK1 knockdown suppressed metastasis to distant organs, including
      lung, liver, and spleen, and inhibited focal adhesion reorganization. Our study
      provides comprehensive information on the molecular determinants of tumor cell
      migration and suggests that SRPK1 has potential as a drug target for limiting
      breast cancer metastasis. 

PMID- 25774503
TI  - STAT3 upregulation in pituitary somatotroph adenomas induces growth hormone
      hypersecretion.
AB  - Pituitary somatotroph adenomas result in dysregulated growth hormone (GH)
      hypersecretion and acromegaly; however, regulatory mechanisms that promote GH
      hypersecretion remain elusive. Here, we provide evidence that STAT3 directly
      induces somatotroph tumor cell GH. Evaluation of pituitary tumors revealed that
      STAT3 expression was enhanced in human GH-secreting adenomas compared with that
      in nonsecreting pituitary tumors. Moreover, STAT3 and GH expression were
      concordant in a somatotroph adenoma tissue array. Promoter and expression
      analysis in a GH-secreting rat cell line (GH3) revealed that STAT3 specifically
      binds the Gh promoter and induces transcription. Stable expression of STAT3 in
      GH3 cells induced expression of endogenous GH, and expression of a constitutively
      active STAT3 further enhanced GH production. Conversely, expression of dominant
      negative STAT3 abrogated GH expression. In primary human somatotroph adenoma
      derived cell cultures, STAT3 suppression with the specific inhibitor S3I-201
      attenuated GH transcription and reduced GH secretion in the majority of
      derivative cultures. In addition, S3I-201 attenuated somatotroph tumor growth and
      GH secretion in a rat xenograft model. GH induced STAT3 phosphorylation and
      nuclear translocation, indicating a positive feedback loop between STAT3 and GH
      in somatotroph tumor cells. Together, these results indicate that adenoma GH
      hypersecretion is the result of STAT3-dependent GH induction, which in turn
      promotes STAT3 expression, and suggest STAT3 as a potential therapeutic target
      for pituitary somatotroph adenomas. 

PMID- 25774504
TI  - Maternal anti-platelet beta3 integrins impair angiogenesis and cause intracranial
      hemorrhage.
AB  - Fetal and neonatal alloimmune thrombocytopenia (FNAIT) is a life-threatening
      disease in which intracranial hemorrhage (ICH) is the major risk. Although
      thrombocytopenia, which is caused by maternal antibodies against beta3 integrin
      and occasionally by maternal antibodies against other platelet antigens, such as
      glycoprotein GPIbalpha, has long been assumed to be the cause of bleeding, the
      mechanism of ICH has not been adequately explored. Utilizing murine models of
      FNAIT and a high-frequency ultrasound imaging system, we found that ICH only
      occurred in fetuses and neonates with anti-beta3 integrin-mediated, but not anti
      GPIbalpha-mediated, FNAIT, despite similar thrombocytopenia in both groups. Only
      anti-beta3 integrin-mediated FNAIT reduced brain and retina vessel density,
      impaired angiogenic signaling, and increased endothelial cell apoptosis, all of
      which were abrogated by maternal administration of intravenous immunoglobulin
      (IVIG). ICH and impairment of retinal angiogenesis were further reproduced in
      neonates by injection of anti-beta3 integrin, but not anti-GPIbalpha antisera.
      Utilizing cultured human endothelial cells, we found that cell proliferation,
      network formation, and AKT phosphorylation were inhibited only by murine anti
      beta3 integrin antisera and human anti-HPA-1a IgG purified from mothers with
      FNAIT children. Our data suggest that fetal hemostasis is distinct and that
      impairment of angiogenesis rather than thrombocytopenia likely causes FNAIT
      associated ICH. Additionally, our results indicate that maternal IVIG therapy can
      effectively prevent this devastating disorder. 

PMID- 25774505
TI  - Resetting the transcription factor network reverses terminal chronic hepatic
      failure.
AB  - The cause of organ failure is enigmatic for many degenerative diseases, including
      end-stage liver disease. Here, using a CCl4-induced rat model of irreversible and
      fatal hepatic failure, which also exhibits terminal changes in the extracellular
      matrix, we demonstrated that chronic injury stably reprograms the critical
      balance of transcription factors and that diseased and dedifferentiated cells can
      be returned to normal function by re-expression of critical transcription
      factors, a process similar to the type of reprogramming that induces somatic
      cells to become pluripotent or to change their cell lineage. Forced re-expression
      of the transcription factor HNF4alpha induced expression of the other hepatocyte
      expressed transcription factors; restored functionality in terminally diseased
      hepatocytes isolated from CCl4-treated rats; and rapidly reversed fatal liver
      failure in CCl4-treated animals by restoring diseased hepatocytes rather than
      replacing them with new hepatocytes or stem cells. Together, the results of our
      study indicate that disruption of the transcription factor network and cellular
      dedifferentiation likely mediate terminal liver failure and suggest reinstatement
      of this network has therapeutic potential for correcting organ failure without
      cell replacement.

PMID- 25774506
TI  - BMP-driven NRF2 activation in esophageal basal cell differentiation and
      eosinophilic esophagitis.
AB  - Tissue homeostasis requires balanced self-renewal and differentiation of
      stem/progenitor cells, especially in tissues that are constantly replenished like
      the esophagus. Disruption of this balance is associated with pathological
      conditions, including eosinophilic esophagitis (EoE), in which basal progenitor
      cells become hyperplastic upon proinflammatory stimulation. However, how basal
      cells respond to the inflammatory environment at the molecular level remains
      undetermined. We previously reported that the bone morphogenetic protein (BMP)
      signaling pathway is critical for epithelial morphogenesis in the embryonic
      esophagus. Here, we address how this pathway regulates tissue homeostasis and EoE
      development in the adult esophagus. BMP signaling was specifically activated in
      differentiated squamous epithelium, but not in basal progenitor cells, which
      express the BMP antagonist follistatin. Previous reports indicate that increased
      BMP activity promotes Barrett's intestinal differentiation; however, in mice,
      basal progenitor cell-specific expression of constitutively active BMP promoted
      squamous differentiation. Moreover, BMP activation increased intracellular ROS
      levels, initiating an NRF2-mediated oxidative response during basal progenitor
      cell differentiation. In both a mouse EoE model and human biopsies, reduced
      squamous differentiation was associated with high levels of follistatin and
      disrupted BMP/NRF2 pathways. We therefore propose a model in which normal
      squamous differentiation of basal progenitor cells is mediated by BMP-driven NRF2
      activation and basal cell hyperplasia is promoted by disruption of BMP signaling
      in EoE. 

PMID- 25774507
TI  - Atypicalities in perceptual adaptation in autism do not extend to perceptual
      causality.
AB  - A recent study showed that adaptation to causal events (collisions) in adults
      caused subsequent events to be less likely perceived as causal. In this study, we
      examined if a similar negative adaptation effect for perceptual causality occurs
      in children, both typically developing and with autism. Previous studies have
      reported diminished adaptation for face identity, facial configuration and gaze
      direction in children with autism. To test whether diminished adaptive coding
      extends beyond high-level social stimuli (such as faces) and could be a general
      property of autistic perception, we developed a child-friendly paradigm for
      adaptation of perceptual causality. We compared the performance of 22 children
      with autism with 22 typically developing children, individually matched on age
      and ability (IQ scores). We found significant and equally robust adaptation
      aftereffects for perceptual causality in both groups. There were also no
      differences between the two groups in their attention, as revealed by reaction
      times and accuracy in a change-detection task. These findings suggest that
      adaptation to perceptual causality in autism is largely similar to typical
      development and, further, that diminished adaptive coding might not be a general
      characteristic of autism at low levels of the perceptual hierarchy, constraining
      existing theories of adaptation in autism. 

PMID- 25774508
TI  - Postural sway and gaze can track the complex motion of a visual target.
AB  - Variability is an inherent and important feature of human movement. This
      variability has form exhibiting a chaotic structure. Visual feedback training
      using regular predictive visual target motions does not take into account this
      essential characteristic of the human movement, and may result in task specific
      learning and loss of visuo-motor adaptability. In this study, we asked how well
      healthy young adults can track visual target cues of varying degree of complexity
      during whole-body swaying in the Anterior-Posterior (AP) and Medio-Lateral (ML)
      direction. Participants were asked to track three visual target motions: a
      complex (Lorenz attractor), a noise (brown) and a periodic (sine) moving target
      while receiving online visual feedback about their performance. Postural sway,
      gaze and target motion were synchronously recorded and the degree of force-target
      and gaze-target coupling was quantified using spectral coherence and Cross
      Approximate entropy. Analysis revealed that both force-target and gaze-target
      coupling was sensitive to the complexity of the visual stimuli motions. Postural
      sway showed a higher degree of coherence with the Lorenz attractor than the brown
      noise or sinusoidal stimulus motion. Similarly, gaze was more synchronous with
      the Lorenz attractor than the brown noise and sinusoidal stimulus motion. These
      results were similar regardless of whether tracking was performed in the AP or ML
      direction. Based on the theoretical model of optimal movement variability
      tracking of a complex signal may provide a better stimulus to improve visuo-motor
      adaptation and learning in postural control. 

PMID- 25774509
TI  - Evaluation of a viral microarray based on simultaneous extraction and
      amplification of viral nucleotide acid for detecting human herpesviruses and
      enteroviruses.
AB  - In this study, a viral microarray based assay was developed to detect the human
      herpesviruses and enteroviruses associated with central nervous system
      infections, including herpes simplex virus type 1, type 2 (HSV1 and HSV2),
      Epstein-Barr virus (EBV), cytomegalovirus (CMV), enterovirus 71 (EV71),
      coxsackievirus A 16 (CA16) and B 5(CB5). The DNA polymerase gene of human
      herpesviruses and 5'-untranslated region of enteroviruses were selected as the
      targets to design primers and probes. Human herpesviruses DNA and enteroviruses
      RNA were extracted simultaneously by using a guanidinium thiocyanate acid buffer,
      and were subsequently amplified through a biotinylated asymmetry multiplex RT-PCR
      with the specific primer of enteroviruses. In total, 90 blood samples and 49
      cerebrospinal fluids samples with suspected systemic or neurological virus
      infections were investigated. Out of 139 samples, 66 were identified as positive.
      The specificities of this multiplex RT-PCR microarray assay were over 96% but the
      sensitivities were various from 100% for HSV1, HSV2, EV71 and CB5, 95.83% for
      CMV, 80% for EBV to 71.43% for CA16 in comparison with reference standards of
      TaqMan qPCR/qRT-PCR. The high Kappa values (>0.90) from HSV1, HSV2, CMV, EV71 and
      CB5 were obtained, indicating almost perfect agreement in term of the 5 viruses
      detection. But lower Kappa values for EBV (0.63) and CA16 (0.74) displayed a
      moderate to substantial agreement. This study provides an innovation of
      simultaneous extraction, amplification, hybridization and detection of DNA
      viruses and RNA viruses with simplicity and specificity, and demonstrates a
      potential clinical utility for a variety of viruses' detection. 

PMID- 25774511
TI  - Correction: using ROC curves to choose minimally important change thresholds when
      sensitivity and specificity are valued equally: the forgotten lesson of
      pythagoras. theoretical considerations and an example application of change in
      health status.

PMID- 25774510
TI  - Causal drift, robust signaling, and complex disease.
AB  - The phenotype of many regulatory circuits in which mutations can cause complex,
      polygenic diseases is to some extent robust to DNA mutations that affect circuit
      components. Here I demonstrate how such mutational robustness can prevent the
      discovery of genetic disease determinants. To make my case, I use a mathematical
      model of the insulin signaling pathway implicated in type 2 diabetes, whose
      signaling output is governed by 15 genetically determined parameters. Using
      multiple complementary measures of a parameter's importance for this phenotype, I
      show that any one disease determinant that is crucial in one genetic background
      will be virtually irrelevant in other backgrounds. In an evolving population that
      drifts through the parameter space of this or other robust circuits through DNA
      mutations, the genetic changes that can cause disease will vary randomly over
      time. I call this phenomenon causal drift. It means that mutations causing
      disease in one (human or non-human) population may have no effect in another
      population, and vice versa. Causal drift casts doubt on our ability to infer the
      molecular mechanisms of complex diseases from non-human model organisms. 

PMID- 25774512
TI  - A novel multiplex PCR discriminates Bacillus anthracis and its genetically
      related strains from other Bacillus cereus group species.
AB  - Anthrax is an important zoonotic disease worldwide that is caused by Bacillus
      anthracis, a spore-forming pathogenic bacterium. A rapid and sensitive method to
      detect B. anthracis is important for anthrax risk management and control in
      animal cases to address public health issues. However, it has recently become
      difficult to identify B. anthracis by using previously reported molecular-based
      methods because of the emergence of B. cereus, which causes severe extra
      intestinal infection, as well as the human pathogenic B. thuringiensis, both of
      which are genetically related to B. anthracis. The close genetic relation of
      chromosomal backgrounds has led to complexity of molecular-based diagnosis. In
      this study, we established a B. anthracis multiplex PCR that can screen for the
      presence of B. anthracis virulent plasmids and differentiate B. anthracis and its
      genetically related strains from other B. cereus group species. Six sets of
      primers targeting a chromosome of B. anthracis and B. anthracis-like strains, two
      virulent plasmids, pXO1 and pXO2, a bacterial gene, 16S rRNA gene, and a
      mammalian gene, actin-beta gene, were designed. The multiplex PCR detected
      approximately 3.0 CFU of B. anthracis DNA per PCR reaction and was sensitive to
      B. anthracis. The internal control primers also detected all bacterial and
      mammalian DNAs examined, indicating the practical applicability of this assay as
      it enables monitoring of appropriate amplification. The assay was also applied
      for detection of clinical strains genetically related to B. anthracis, which were
      B. cereus strains isolated from outbreaks of hospital infections in Japan, and
      field strains isolated in Zambia, and the assay differentiated B. anthracis and
      its genetically related strains from other B. cereus group strains. Taken
      together, the results indicate that the newly developed multiplex PCR is a
      sensitive and practical method for detecting B. anthracis. 

PMID- 25774513
TI  - Retinal vein occlusion and pregnancy, pre-eclampsia, and eclampsia: the results
      from a nationwide, population-based study using the national claim database.
AB  - OBJECTIVE: To investigate the incidence of retinal vein occlusion (RVO) in
      pregnant women and in the subpopulation of pregnant women with pre
      eclampsia/eclampsia compared to that in the age-matched general female population
      to determine if there is increased risk of RVO in pregnancy. DESIGN: Nationwide
      population-based retrospective study using data entered into the Korean national
      health claims database from 2007 to 2011. SETTING AND PARTICIPANTS: Of the
      incident RVO cases in the database, RVO cases that occurred during the pregnancy
      associated period, which spanned a 52-week period from 40-weeks-before to 12
      weeks-after childbirth, were identified. Of these cases, the presence of pre
      eclampsia/eclampsia was determined. MAIN OUTCOME AND MEASURE: The standardized
      incidence ratios (SIRs) of RVO in the general pregnant population and in the
      pregnant population with pre-eclampsia/eclampsia were determined with respect to
      the age-matched general female population. RESULTS: Pregnancy-related RVO was
      identified in 33 cases from the 1.8 million women who experience childbirth
      during the study period, while the expected number of cases calculated by the
      direct standardization to the age-matched general population was 113. Of the 33
      patients, 12 patients (36.4%) had pre-eclampsia or eclampsia. The SIR for the
      general pregnant population in reference to the age-matched general female
      population was 0.29 (95% CI, 0.20-0.41). In contrast, the SIR for the pregnant
      population with pre-eclampsia/eclampsia in reference to the age-matched general
      female population and the age-matched general pregnant population was 67.50 (95%
      CI, 34.88-117.92) and 246.50 (95% CI, 127.37-430.59), respectively. CONCLUSIONS
      AND RELEVANCE: The results suggest that pre-eclampsia/eclampsia is a risk factor
      for RVO, while pregnancy itself may not be a risk factor for RVO.

PMID- 25774514
TI  - Tissue elasticity regulated tumor gene expression: implication for diagnostic
      biomarkers of primitive neuroectodermal tumor.
AB  - BACKGROUND: The tumor microenvironment consists of both physical and chemical
      factors. Tissue elasticity is one physical factor contributing to the
      microenvironment of tumor cells. To test the importance of tissue elasticity in
      cell culture, primitive neuroectodermal tumor (PNET) stem cells were cultured on
      soft polyacrylamide (PAA) hydrogel plates that mimics the elasticity of brain
      tissue compared with PNET on standard polystyrene (PS) plates. We report the
      molecular profiles of PNET grown on either PAA or PS. METHODOLOGY/PRINCIPAL
      FINDINGS: A whole-genome microarray profile of transcriptional expression between
      the two culture conditions was performed as a way to probe effects of substrate
      on cell behavior in culture. The results showed more genes downregulated on PAA
      compared to PS. This led us to propose microRNA (miRNA) silencing as a potential
      mechanism for downregulation. Bioinformatic analysis predicted a greater number
      of miRNA binding sites from the 3' UTR of downregulated genes and identified as
      specific miRNA binding sites that were enriched when cells were grown on PAA-this
      supports the hypothesis that tissue elasticity plays a role in influencing miRNA
      expression. Thus, Dicer was examined to determine if miRNA processing was
      affected by tissue elasticity. Dicer genes were downregulated on PAA and had
      multiple predicted miRNA binding sites in its 3' UTR that matched the miRNA
      binding sites found enriched on PAA. Many differentially regulated genes were
      found to be present on PS but downregulated on PAA were mapped onto intron
      sequences. This suggests expression of alternative polyadenylation sites within
      intron regions that provide alternative 3' UTRs and alternative miRNA binding
      sites. This results in tissue specific transcriptional downregulation of mRNA in
      humans by miRNA. We propose a mechanism, driven by the physical characteristics
      of the microenvironment by which downregulation of genes occur. We found that
      tissue elasticity-mediated cytokines (TGFbeta2 and TNFalpha) signaling affect
      expression of ECM proteins. CONCLUSIONS: Our results suggest that tissue
      elasticity plays important roles in miRNA expression, which, in turn, regulate
      tumor growth or tumorigenicity.

PMID- 25774515
TI  - Spatiotemporal regulation of a Legionella pneumophila T4SS substrate by the
      metaeffector SidJ.
AB  - Modulation of host cell function is vital for intracellular pathogens to survive
      and replicate within host cells. Most commonly, these pathogens utilize
      specialized secretion systems to inject substrates (also called effector
      proteins) that function as toxins within host cells. Since it would be
      detrimental for an intracellular pathogen to immediately kill its host cell, it
      is essential that secreted toxins be inactivated or degraded after they have
      served their purpose. The pathogen Legionella pneumophila represents an ideal
      system to study interactions between toxins as it survives within host cells for
      approximately a day and its Dot/Icm type IVB secretion system (T4SS) injects a
      vast number of toxins. Previously we reported that the Dot/Icm substrates SidE,
      SdeA, SdeB, and SdeC (known as the SidE family of effectors) are secreted into
      host cells, where they localize to the cytoplasmic face of the Legionella
      containing vacuole (LCV) in the early stages of infection. SidJ, another effector
      that is unrelated to the SidE family, is also encoded in the sdeC-sdeA locus.
      Interestingly, while over-expression of SidE family proteins in a wild type
      Legionella strain has no effect, we found that their over-expression in a ?sidJ
      mutant completely inhibits intracellular growth of the strain. In addition, we
      found expression of SidE proteins is toxic in both yeast and mammalian HEK293
      cells, but this toxicity can be suppressed by co-expression of SidJ, suggesting
      that SidJ may modulate the function of SidE family proteins. Finally, we were
      able to demonstrate both in vivo and in vitro that SidJ acts on SidE proteins to
      mediate their disappearance from the LCV, thereby preventing lethal intoxication
      of host cells. Based on these findings, we propose that SidJ acts as a
      metaeffector to control the activity of other Legionella effectors. 

PMID- 25774516
TI  - Distribution and maintenance of histone H3 lysine 36 trimethylation in
      transcribed locus.
AB  - Post-translational modifications of core histones play an important role in the
      epigenetic regulation of chromatin dynamics and gene expression. In Saccharomyces
      cerevisiae methylation marks at K4, K36, and K79 of histone H3 are associated
      with gene transcription. Although Set2-mediated H3K36 methylation is enriched
      throughout the coding region of active genes and prevents aberrant
      transcriptional initiation within coding sequences, it is not known if
      transcription of one locus impacts the methylation pattern of neighbouring areas
      and for how long H3K36 methylation is maintained after transcription termination.
      Our results demonstrate that H3K36 methylation is restricted to the transcribed
      sequence only and the modification does not spread to adjacent loci downstream
      from transcription termination site. We also show that H3K36 trimethylation mark
      persists in the locus for at least 60 minutes after transcription inhibition,
      suggesting a short epigenetic memory for recently occurred transcriptional
      activity. Our results indicate that both replication-dependent exchange of
      nucleosomes and the activity of histone demethylases Rph1, Jhd1 and Gis1
      contribute to the turnover of H3K36 methylation upon shut-down of transcription. 

PMID- 25774517
TI  - H-Ras mediates the inhibitory effect of epidermal growth factor on the epithelial
      Na+ channel.
AB  - The present study investigates the role of small G-proteins of the Ras family in
      the epidermal growth factor (EGF)-activated cellular signalling pathway that
      downregulates activity of the epithelial Na+ channel (ENaC). We found that H-Ras
      is a key component of this EGF-activated cellular signalling mechanism in M1
      mouse collecting duct cells. Expression of a constitutively active H-Ras mutant
      inhibited the amiloride-sensitive current. The H-Ras-mediated signalling pathway
      that inhibits activity of ENaC involves c-Raf, and that the inhibitory effect of
      H-Ras on ENaC is abolished by the MEK1/2 inhibitor, PD98059. The inhibitory
      effect of H-Ras is not mediated by Nedd4-2, a ubiquitin protein ligase that
      regulates the abundance of ENaC at the cell surface membrane, or by a negative
      effect of H-Ras on proteolytic activation of the channel. The inhibitory effects
      of EGF and H-Ras on ENaC, however, were not observed in cells in which expression
      of caveolin-1 (Cav-1) had been knocked down by siRNA. These findings suggest that
      the inhibitory effect of EGF on ENaC-dependent Na+ absorption is mediated via the
      H-Ras/c-Raf, MEK/ERK signalling pathway, and that Cav-1 is an essential component
      of this EGF-activated signalling mechanism. Taken together with reports that mice
      expressing a constitutive mutant of H-Ras develop renal cysts, our findings
      suggest that H-Ras may play a key role in the regulation of renal ion transport
      and renal development. 

PMID- 25774518
TI  - Risk factors for the presence of chikungunya and dengue vectors (Aedes aegypti
      and Aedes albopictus), their altitudinal distribution and climatic determinants
      of their abundance in central Nepal.
AB  - BACKGROUND: The presence of the recently introduced primary dengue virus vector
      mosquito Aedes aegypti in Nepal, in association with the likely indigenous
      secondary vector Aedes albopictus, raises public health concerns. Chikungunya
      fever cases have also been reported in Nepal, and the virus causing this disease
      is also transmitted by these mosquito species. Here we report the results of a
      study on the risk factors for the presence of chikungunya and dengue virus
      vectors, their elevational ceiling of distribution, and climatic determinants of
      their abundance in central Nepal. METHODOLOGY/PRINCIPAL FINDINGS: We collected
      immature stages of mosquitoes during six monthly cross-sectional surveys covering
      six administrative districts along an altitudinal transect in central Nepal that
      extended from Birgunj (80 m above sea level [asl]) to Dhunche (highest altitude
      sampled: 2,100 m asl). The dengue vectors Ae. aegypti and Ae. albopictus were
      commonly found up to 1,350 m asl in Kathmandu valley and were present but rarely
      found from 1,750 to 2,100 m asl in Dhunche. The lymphatic filariasis vector Culex
      quinquefasciatus was commonly found throughout the study transect. Physiographic
      region, month of collection, collection station and container type were
      significant predictors of the occurrence and co-occurrence of Ae. aegypti and Ae.
      albopictus. The climatic variables rainfall, temperature, and relative humidity
      were significant predictors of chikungunya and dengue virus vectors abundance.
      CONCLUSIONS/SIGNIFICANCE: We conclude that chikungunya and dengue virus vectors
      have already established their populations up to the High Mountain region of
      Nepal and that this may be attributed to the environmental and climate change
      that has been observed over the decades in Nepal. The rapid expansion of the
      distribution of these important disease vectors in the High Mountain region,
      previously considered to be non-endemic for dengue and chikungunya fever, calls
      for urgent actions to protect the health of local people and tourists travelling
      in the central Himalayas.

PMID- 25774519
TI  - Identification, evolution and expression of an insulin-like peptide in the
      cephalochordate Branchiostoma lanceolatum.
AB  - Insulin is one of the most studied proteins since it is central to the regulation
      of carbohydrate and fat metabolism in vertebrates and its expression and release
      are disturbed in diabetes, the most frequent human metabolic disease worldwide.
      However, the evolution of the function of the insulin protein family is still
      unclear. In this study, we present a phylogenetic and developmental analysis of
      the Insulin Like Peptide (ILP) in the cephalochordate amphioxus. We identified an
      ILP in the European amphioxus Branchiostoma lanceolatum that displays structural
      characteristics of both vertebrate insulin and Insulin-like Growth Factors
      (IGFs). Our phylogenetic analysis revealed that amphioxus ILP represents the
      sister group of both vertebrate insulin and IGF proteins. We also characterized
      both temporal and spatial expression of ILP in amphioxus. We show that ilp is
      highly expressed in endoderm and paraxial mesoderm during development, and mainly
      expressed in the gut of both the developing embryo and adult. We hypothesize that
      ILP has critical implications in both developmental processes and metabolism and
      could display IGF- and insulin-like functions in amphioxus supporting the idea of
      a common ancestral protein. 

PMID- 25774520
TI  - Breast cancer screening in Saudi Arabia: free but almost no takers.
AB  - INTRODUCTION: Mammography ensures early diagnosis and a better chance for
      treatment and recovery from breast cancer. We conducted a national survey to
      investigate knowledge and practices of breast cancer screening among Saudi women
      aged 50 years or older in order to inform the breast cancer national health
      programs. MATERIALS AND METHODS: The Saudi Health Interview Survey is a national
      multistage survey of individuals aged 15 years or older. The survey included
      questions on socio-demographic characteristics, tobacco consumption, diet,
      physical activity, health-care utilization, different health-related behaviors,
      and self-reported chronic conditions. Female respondents were asked about
      knowledge and practices of self and clinical breast exams, as well as
      mammography. RESULTS: Between April and June 2013, a total of 10,735 participants
      completed the survey. Among respondents, 1,135 were women aged 50 years or older
      and were included in this analysis. About 89% of women reported not having a
      clinical breast exam in the past year, and 92% reported never having a mammogram.
      Women living in Al Sharqia had the highest rate of mammography use. Women who
      were educated, those who had received a routine medical exam within the last two
      years, and those who were diagnosed with hypertension were more likely to have
      had a mammogram in the past two years. DISCUSSION: Our results show very low
      rates of breast cancer screening in the Kingdom of Saudi Arabia, a country with
      free health services. This calls for educational campaigns to improve breast
      cancer screening. Addressing the barriers for breast cancer screening is a public
      health imperative.

PMID- 25774521
TI  - The relationship between birth weight, adiposity rebound and overweight at the
      age of 17 years (results of the Lithuanian longitudinal growth study, 1990 -
      2008).
AB  - The purpose of this study was to investigate the relationship between overweight
      and obesity at the age of 17 years with a birth weight and time of an adiposity
      rebound. The results were based on data (N = 1535) collected from the personal
      health records of children born in 1990 in Vilnius city and region. The further
      growth of newborns with normal (3000 - 3999 g), suboptimal (2500 - 2999 g) and
      large (>= 4000 g) birth weight was analyzed. Statistically significant results (p
      < 0.05) were obtained in girls: at the age of 17, the BMI of suboptimal, normal
      and large birth weight females was 19.87 +/- 2.23 kg/m2, 20.98 +/- 2.78 kg/m2 and
      22.20 +/- 3.52 kg/m2 respectively. We also found that children with large birth
      weight had the highest risk to become overweight or obese later in their life.
      Both boys and girls overweight at the age of 17 had an earlier adiposity rebound
      (at the age of 5 years) in comparison with non-overweight children (their
      adiposity rebound had happened at the age of 6 - 7 years). However, the majority
      of children with an early adiposity rebound did not become overweight on the
      subsequent age period at once - it might happen later, already at the
      adolescence. Thus it is very important to carefully screen the growth of
      preschool children and start preventive measures against the overweight and
      obesity as early as possible.

PMID- 25774522
TI  - Combining genetic and demographic data for the conservation of a Mediterranean
      marine habitat-forming species.
AB  - The integration of ecological and evolutionary data is highly valuable for
      conservation planning. However, it has been rarely used in the marine realm,
      where the adequate design of marine protected areas (MPAs) is urgently needed.
      Here, we examined the interacting processes underlying the patterns of genetic
      structure and demographic strucuture of a highly vulnerable Mediterranean habitat
      forming species (i.e. Paramuricea clavata (Risso, 1826)), with particular
      emphasis on the processes of contemporary dispersal, genetic drift, and
      colonization of a new population. Isolation by distance and genetic
      discontinuities were found, and three genetic clusters were detected; each
      submitted to variations in the relative impact of drift and gene flow. No founder
      effect was found in the new population. The interplay of ecology and evolution
      revealed that drift is strongly impacting the smallest, most isolated
      populations, where partial mortality of individuals was highest. Moreover, the
      eco-evolutionary analyses entailed important conservation implications for P.
      clavata. Our study supports the inclusion of habitat-forming organisms in the
      design of MPAs and highlights the need to account for genetic drift in the
      development of MPAs. Moreover, it reinforces the importance of integrating
      genetic and demographic data in marine conservation. 

PMID- 25774523
TI  - C5b-9-targeted molecular MR imaging in rats with Heymann nephritis: a new
      approach in the evaluation of nephrotic syndrome.
AB  - Membranous nephropathy (MN) is the major cause of adult nephrotic syndrome, which
      severely affects patients' quality of life. Currently, percutaneous renal biopsy
      is required to definitively diagnose MN. However, this technique is invasive and
      may cause severe complications. Therefore, an urgent clinical need exists for
      dynamic noninvasive monitoring of the renal state. In-depth molecular imaging
      studies could assist in finding a solution. Membrane attack complex C5b-9 is the
      key factor in the development of MN, and this protein primarily deposits in the
      glomerulus. The present study bound polyclonal antibodies to C5b-9 with
      ultrasmall superparamagnetic iron oxide (USPIO) nanoparticles to obtain C5b-9
      targeted magnetic resonance molecular imaging probes. The probes were injected
      intravenously into rats with Heymann nephritis, a classic disease model of MN.
      The signal intensity in the T2*-weighted imaging of kidneys in vivo using 7.0
      Tesla magnetic resonance imaging decreased significantly 24 hours after injection
      compared to the untargeted and control groups. This signal change was consistent
      with the finding of nanoparticle deposits in pathological glomeruli. This study
      demonstrated a novel molecular imaging technique for the assessment of MN. 

PMID- 25774524
TI  - Mitochondrial DNA released by trauma induces neutrophil extracellular traps.
AB  - Neutrophil extracellular traps (NETs) are critical for anti-bacterial activity of
      the innate immune system. We have previously shown that mitochondrial damage
      associated molecular patterns (mtDAMPs), including mitochondrial DNA (mtDNA), are
      released into the circulation after injury. We therefore questioned whether mtDNA
      is involved in trauma-induced NET formation. Treatment of human
      polymorphoneutrophils (PMN) with mtDNA induced robust NET formation, though in
      contrast to phorbol myristate acetate (PMA) stimulation, no NADPH-oxidase
      involvement was required. Moreover, formation of mtDNA-induced NETs was
      completely blocked by TLR9 antagonist, ODN-TTAGGG. Knowing that infective
      outcomes of trauma in elderly people are more severe than in young people, we
      measured plasma mtDNA and NET formation in elderly and young trauma patients and
      control subjects. MtDNA levels were significantly higher in the plasma of elderly
      trauma patients than young patients, despite lower injury severity scores in the
      elderly group. NETs were not visible in circulating PMN isolated from either
      young or old control subjects. NETs were however, detected in PMN isolated from
      young trauma patients and to a lesser extent from elderly patients. Stimulation
      by PMA induced widespread NET formation in PMN from both young volunteers and
      young trauma patients. NET response to PMA was much less pronounced in both
      elderly volunteers' PMN and in trauma patients' PMN. We conclude that mtDNA is a
      potent inducer of NETs that activates PMN via TLR9 without NADPH-oxidase
      involvement. We suggest that decreased NET formation in the elderly regardless of
      higher mtDNA levels in their plasma may result from decreased levels of TLR9
      and/or other molecules, such as neutrophil elastase and myeloperoxidase that are
      involved in NET generation. Further study of the links between circulating mtDNA
      and NET formation may elucidate the mechanisms of trauma-related organ failure as
      well as the greater susceptibility to secondary infection in elderly trauma
      patients. 

PMID- 25774525
TI  - Association between physical activity and teacher-reported academic performance
      among fifth-graders in Shanghai: a quantile regression.
AB  - INTRODUCTION: A growing body of literature reveals the causal pathways between
      physical activity and brain function, indicating that increasing physical
      activity among children could improve rather than undermine their scholastic
      performance. However, past studies of physical activity and scholastic
      performance among students often relied on parent-reported grade information, and
      did not explore whether the association varied among different levels of
      scholastic performance. Our study among fifth-grade students in Shanghai sought
      to determine the association between regular physical activity and teacher
      reported academic performance scores (APS), with special attention to the
      differential associational patterns across different strata of scholastic
      performance. METHOD: A total of 2,225 students were chosen through a stratified
      random sampling, and a complete sample of 1470 observations were used for
      analysis. We used a quantile regression analysis to explore whether the
      association between physical activity and teacher-reported APS differs by
      distribution of APS. RESULTS: Minimal-intensity physical activity such as walking
      was positively associated with academic performance scores (beta = 0.13, SE =
      0.04). The magnitude of the association tends to be larger at the lower end of
      the APS distribution (beta = 0.24, SE = 0.08) than in the higher end of the
      distribution (beta = 0.00, SE = 0.07). CONCLUSION: Based upon teacher-reported
      student academic performance, there is no evidence that spending time on frequent
      physical activity would undermine student's APS. Those students who are below the
      average in their academic performance could be worse off in academic performance
      if they give up minimal-intensity physical activity. Therefore, cutting physical
      activity time in schools could hurt the scholastic performance among those
      students who were already at higher risk for dropping out due to inadequate APS.

PMID- 25774526
TI  - Patients lacking sustainable long-term weight loss after gastric bypass surgery
      show signs of decreased inhibitory control of prepotent responses.
AB  - BACKGROUND: A considerable number of bariatric patients report poor long-term
      weight loss after Roux-en-Y gastric bypass (RYGB) surgery. One possibility for an
      underlying cause is an impairment of cognitive control that impedes this patient
      group's dietary efforts. OBJECTIVE: To investigate if patients having either poor
      or good weight loss response, ~12 years after RYGB-surgery, differ in their
      ability to inhibit prepotent responses when processing food cues during
      attentional operations-as measure of cognitive control. METHODS: In terms of
      weight loss following RYGB-surgery, 15 'poor responders' and 15 'good
      responders', matched for gender, age, education, preoperative body mass index,
      and years since surgery, were administered two tasks that measure sustained
      attention and response control: a go/no-go task and a Stroop interference task;
      both of which are associated with maladaptive eating behaviours. RESULTS: The
      poor responders (vs. good responders) needed significantly more time when
      conducting a go/no-go task (603+/-134 vs. 519+/-44 msec, p = 0.03), but the
      number of errors did not differ between groups. When conducting a Stroop
      interference task, poor responders read fewer inks than good responders (68+/-16
      vs. 85+/-10 words, p = 0.002). CONCLUSION: Patients lacking sustainable weight
      loss after RYGB-surgery showed poorer inhibitory control than patients that
      successfully lost weight. In the authors' view, these results suggest that
      cognitive behavioral therapies post-RYGB-surgery may represent a promising
      behavioral adjuvant to achieve sustainable weight loss in patients undergoing
      this procedure. Future studies should examine whether these control deficits in
      poor responders are food-specific or not.

PMID- 25774527
TI  - The role of walkers' needs and expectations in supporting maintenance of
      attendance at walking groups: a longitudinal multi-perspective study of walkers
      and walk group leaders.
AB  - BACKGROUND: There is good evidence that when people's needs and expectations
      regarding behaviour change are met, they are satisfied with that change, and
      maintain those changes. Despite this, there is a dearth of research on needs and
      expectations of walkers when initially attending walking groups and whether and
      how these needs and expectations have been satisfied after a period of
      attendance. Equally, there is an absence of research on how people who lead these
      groups understand walkers' needs and walk leaders' actions to address them. The
      present study was aimed at addressing both of these gaps in the research.
      METHODS: Two preliminary thematic analyses were conducted on face-to-face
      interviews with (a) eight walkers when they joined walking groups, five of whom
      were interviewed three months later, and (b) eight walk leaders. A multi
      perspective analysis building upon these preliminary analyses identified
      similarities and differences within the themes that emerged from the interviews
      with walkers and walk leaders. RESULTS: Walkers indicated that their main needs
      and expectations when joining walking groups were achieving long-term social and
      health benefits. At the follow up interviews, walkers indicated that satisfaction
      with meeting similar others within the groups was the main reason for continued
      attendance. Their main source of dissatisfaction was not feeling integrated in
      the existing walking groups. Walk leaders often acknowledged the same reasons for
      walkers joining and maintaining attendance at walking. However, they tended to
      attribute dissatisfaction and drop out to uncontrollable environmental factors
      and/or walkers' personalities. Walk leaders reported a lack of efficacy to
      effectively address walkers' needs. CONCLUSIONS: Interventions to increase
      retention of walkers should train walk leaders with the skills to help them
      modify the underlying psychological factors affecting walkers' maintenance at
      walking groups. This should result in greater retention of walkers in walking
      groups, thereby allowing walkers to receive the long-term social and health
      benefits of participation in these groups.

PMID- 25774528
TI  - Optimal cloning of PCR fragments by homologous recombination in Escherichia coli.
AB  - PCR fragments and linear vectors containing overlapping ends are easily assembled
      into a propagative plasmid by homologous recombination in Escherichia coli.
      Although this gap-repair cloning approach is straightforward, its existence is
      virtually unknown to most molecular biologists. To popularize this method, we
      tested critical parameters influencing the efficiency of PCR fragments cloning
      into PCR-amplified vectors by homologous recombination in the widely used E. coli
      strain DH5alpha. We found that the number of positive colonies after
      transformation increases with the length of overlap between the PCR fragment and
      linear vector. For most practical purposes, a 20 bp identity already ensures high
      cloning yields. With an insert to vector ratio of 2:1, higher colony forming
      numbers are obtained when the amount of vector is in the range of 100 to 250 ng.
      An undesirable cloning background of empty vectors can be minimized during vector
      PCR amplification by applying a reduced amount of plasmid template or by using
      primers in which the 5' termini are separated by a large gap. DpnI digestion of
      the plasmid template after PCR is also effective to decrease the background of
      negative colonies. We tested these optimized cloning parameters during the
      assembly of five independent DNA constructs and obtained 94% positive clones out
      of 100 colonies probed. We further demonstrated the efficient and simultaneous
      cloning of two PCR fragments into a vector. These results support the idea that
      homologous recombination in E. coli might be one of the most effective methods
      for cloning one or two PCR fragments. For its simplicity and high efficiency, we
      believe that recombinational cloning in E. coli has a great potential to become a
      routine procedure in most molecular biology-oriented laboratories. 

PMID- 25774529
TI  - Dynamics of maize carbon contribution to soil organic carbon in association with
      soil type and fertility level.
AB  - Soil type and fertility level influence straw carbon dynamics in the
      agroecosystems. However, there is a limited understanding of the dynamic
      processes of straw-derived and soil-derived carbon and the influence of the
      addition of straw carbon on soil-derived organic carbon in different soils
      associated with different fertility levels. In this study, we applied the in-situ
      carborundum tube method and 13C-labeled maize straw (with and without maize
      straw) at two cropland (Phaeozem and Luvisol soils) experimental sites in
      northeast China to quantify the dynamics of maize-derived and soil-derived carbon
      in soils associated with high and low fertility, and to examine how the addition
      of maize carbon influences soil-derived organic carbon and the interactions of
      soil type and fertility level with maize-derived and soil-derived carbon. We
      found that, on average, the contributions of maize-derived carbon to total
      organic carbon in maize-soil systems during the experimental period were
      differentiated among low fertility Luvisol (from 62.82% to 42.90), high fertility
      Luvisol (from 53.15% to 30.00%), low fertility Phaeozem (from 58.69% to 36.29%)
      and high fertility Phaeozem (from 41.06% to 16.60%). Furthermore, the addition of
      maize carbon significantly decreased the remaining soil-derived organic carbon in
      low and high fertility Luvisols and low fertility Phaeozem before two months.
      However, the increasing differences in soil-derived organic carbon between both
      soils with and without maize straw after two months suggested that maize-derived
      carbon was incorporated into soil-derived organic carbon, thereby potentially
      offsetting the loss of soil-derived organic carbon. These results suggested that
      Phaeozem and high fertility level soils would fix more maize carbon over time and
      thus were more beneficial for protecting soil-derived organic carbon from maize
      carbon decomposition. 

PMID- 25774530
TI  - The association between pre-treatment serum 25-hydroxyvitamin D and survival in
      newly diagnosed stage IV prostate cancer.
AB  - BACKGROUND/AIMS: Emerging evidence in the literature suggests a positive
      association between serum 25-hydroxyvitamin D [25(OH)D], a standard indicator of
      vitamin D status, and survival in certain types of cancer. We investigated this
      relationship in newly diagnosed stage IV prostate cancer patients. METHODS: A
      consecutive cohort of 125 newly diagnosed stage IV prostate cancer patients
      underwent a baseline serum 25(OH)D evaluation prior to receiving any treatment at
      our institution between January 2008 and December 2011. We used the vitamin D
      categories of "deficient (<20 ng/ml)", "insufficient (20 to 32 ng/ml)", and
      "sufficient (>32 ng/ml)". Cox regression was used to evaluate the prognostic
      significance of serum 25(OH)D after adjusting for relevant confounders. RESULTS:
      Mean age at diagnosis was 60 years. Of the 125 patients, 32 (25.6%) were
      deficient, 49 (39.2%) were insufficient and 44 (35.2%) were sufficient in vitamin
      D at the time of diagnosis. The median survival in deficient, insufficient and
      sufficient cohorts was 47.8, 44.0 and 52.6 months respectively (p = 0.60). On
      univariate analysis, four variables demonstrated a statistically significant
      association with survival: nutritional status, bone metastasis, corrected serum
      calcium and serum albumin (p<0.05 for all). On multivariate analysis, five
      variables demonstrated statistically significant associations with survival:
      hospital location, age, bone metastasis, serum albumin and corrected serum
      calcium (p<0.05 for all). Serum vitamin D status was not significant on either
      univariate or multivariate analysis. CONCLUSION: Contrary to previously published
      research, we found no significant association between pre-treatment serum 25(OH)D
      and survival in newly diagnosed stage IV prostate cancer patients. The lack of a
      significant association between serum vitamin D and survival in our study could
      perhaps be due to the fact that the disease was far too advanced in our patients
      for vitamin D levels to have any impact on prognosis.

PMID- 25774532
TI  - Plant trait variation along an altitudinal gradient in mediterranean high
      mountain grasslands: controlling the species turnover effect.
AB  - Assessing changes in plant functional traits along gradients is useful for
      understanding the assembly of communities and their response to global and local
      environmental drivers. However, these changes may reflect the effects of species
      composition (i.e. composition turnover), species abundance (i.e. species
      interaction), and intra-specific trait variability (i.e. species plasticity). In
      order to determine the relevance of the latter, trait variation can be assessed
      under minimal effects of composition turnover. Nine sampling sites were
      established along an altitudinal gradient in a Mediterranean high mountain
      grassland community with low composition turnover (Madrid, Spain; 1940 m-2419 m).
      Nine functional traits were also measured for ten individuals of around ten plant
      species at each site, for a total of eleven species across all sites. The
      relative importance of different sources of variability (within/between site and
      intra-/inter-specific functional diversity) and trait variation at species and
      community level along the considered gradients were explored. We found a weak
      individual species response to altitude and other environmental variables
      although in some cases, individuals were smaller and leaves were thicker at
      higher elevations. This lack of species response was most likely due to greater
      within- than between-site species variation. At the community level, inter
      specific functional diversity was generally greater than the intra-specific
      component except for traits linked to leaf element content (leaf carbon content,
      leaf nitrogen content, delta13C and delta15N). Inter-specific functional
      diversity decreased with lower altitude for four leaf traits (specific leaf area,
      leaf dry matter content, delta13C and delta15N), suggesting trait convergence
      between species at lower elevations, where water shortage may have a stronger
      environmental filtering effect than colder temperatures at higher altitudes. Our
      results suggest that, within a vegetation type encompassing various environmental
      gradients, both, changes in species abundance and intra-specific trait
      variability adjust for the community functional response to environmental
      changes. 

PMID- 25774531
TI  - TatBC-independent TatA/Tat substrate interactions contribute to transport
      efficiency.
AB  - The Tat system can transport folded, signal peptide-containing proteins (Tat
      substrates) across energized membranes of prokaryotes and plant plastids. A twin
      arginine motif in the signal peptide of Tat substrates is recognized by TatC
      containing complexes, and TatA permits the membrane passage. Often, as in the
      model Tat systems of Escherichia coli and plant plastids, a third component -
      TatB - is involved that resembles TatA but has a higher affinity to TatC. It is
      not known why most TatA dissociates from TatBC complexes in vivo and distributes
      more evenly in the membrane. Here we show a TatBC-independent substrate-binding
      to TatA from Escherichia coli, and we provide evidence that this binding enhances
      Tat transport. First hints came from in vivo cross-linking data, which could be
      confirmed by affinity co-purification of TatA with the natural Tat substrates
      HiPIP and NrfC. Two positions on the surface of HiPIP could be identified that
      are important for the TatA interaction and transport efficiency, indicating
      physiological relevance of the interaction. Distributed TatA thus may serve to
      accompany membrane-interacting Tat substrates to the few TatBC spots in the
      cells. 

PMID- 25774533
TI  - Ectoparasites and endoparasites of fish form networks with different structures.
AB  - Hosts and parasites interact with each other in a variety of ways, and this
      diversity of interactions is reflected in the networks they form. To test for
      differences in interaction patterns of ecto- and endoparasites we analysed
      subnetworks formed by each kind of parasites and their host fish species in fish
      parasite networks for 22 localities. We assessed the proportion of parasite
      species per host species, the relationship between parasite fauna composition and
      host taxonomy, connectance, nestedness and modularity of each subnetwork (n =
      44). Furthermore, we evaluated the similarity in host species composition among
      modules in ecto- and endoparasite subnetworks. We found several differences
      between subnetworks of fish ecto- and endoparasites. The association with a
      higher number of host species observed among endoparasites resulted in higher
      connectance and nestedness, and lower values of modularity in their subnetworks
      than in those of ectoparasites. Taxonomically related host species tended to
      share ecto- or endoparasites with the same interaction intensity, but the species
      composition of hosts tended to differ between modules formed by ecto- and
      endoparasites. Our results suggest that different evolutionary and ecological
      processes are responsible for organizing the networks formed by ecto- and
      endoparasites and fish. 

PMID- 25774534
TI  - Mitochondrial dysfunction in titanium dioxide nanoparticle-induced neurotoxicity.
AB  - Nanotechnology has emerged as a field of scientific innovation which has opened
      up a plethora of concerns for the potential impact on human and environment.
      Various toxicological studies have confirmed that nanoparticles (NPs) can be
      potentially hazardous because of their unique small size and physico-chemical
      properties. With the wide applications of titanium dioxide nanoparticles (TNPs)
      in day-to-day life in form of cosmetics, paints, sterilization and so on, there
      is growing concern regarding the deleterious effects of TNPs on central nervous
      system. Mitochondria is an important origin for generation of energy as well as
      free radicals and these free radicals can lead to mitochondrial damage and
      finally lead to apoptosis. The objective of our study was to elucidate the
      potential neurotoxic effect of TNPs in anatase form. Oxidative stress was
      determined by measuring lipid peroxidation and protein carbonyl content which was
      found to be significantly increased. Reduced glutathione content and major
      glutathione metabolizing enzymes were also modulated signifying the role of
      glutathione redox cycle in the pathophysiology of TNPs. Mitochondrial complexes
      were also modulated from the exposure to TNPs. The present study indicates that
      nanosize TNPs may pose a health risk to mitochondrial brain with the generation
      of reactive oxygen species, and thus NPs should be carefully used. 

PMID- 25774535
TI  - Saturated Fats and Cardiovascular Disease: Interpretations Not as Simple as They
      Once Were.
AB  - Historically, the so-called "lipid hypothesis" has focused on the detrimental
      role of saturated fats per se in enhancing the risks of cardiovascular disease.
      Recently, a body of new information and systematic analyses of available data
      have questioned simple interpretation of the relationship of dietary saturated
      fats and of individual saturated fatty acids to CVD risk. Thus, current
      assessments of risks due to dietary fat consumption that emphasize the
      confounding nature of the dietary macronutrients substituted for dietary
      saturated fats and give broader recognition to the effect of patterns of food
      intake as a whole are the most productive approach to an overall healthy diet. 

PMID- 25774536
TI  - Performance of gymnastics skill benefits from an external focus of attention.
AB  - The present study was designed to fill a gap in the literature on attentional
      focus and sports performance. Specifically, in contrast to most previous studies
      in which an external focus was directed at an implement, we used a gymnastics
      skill that did not involve the use of an implement. Furthermore, while most
      studies used only outcome measures of performance, we also assessed movement
      quality. Twelve-year-old gymnasts performed a maximum vertical jump with a 180
      degree turn while airborne, with their hands crossing in front of their chest
      during the turn under three different focus conditions. Under the external focus
      condition, participants were asked to focus on the direction in which a tape
      marker, which was attached to their chest, was pointing after the turn. Under the
      internal focus condition, they were asked to focus on the direction in which
      their hands were pointing after the turn. Under the control condition, no focus
      instructions were given. The external focus condition resulted in both superior
      movement form and greater jump height than did the other two conditions, which
      produced comparable results. The present findings show that, similar to other
      tasks, the performance of form-based skills can be enhanced relatively easily by
      appropriate external focus instructions. 

PMID- 25774537
TI  - Conservative management of preterm premature rupture of membranes beyond 32
      weeks' gestation: is it worthwhile?
AB  - We aimed to investigate whether conservative management of preterm premature
      rupture of membranes (PPROM) at 32-34 weeks' gestation improves outcome. In this
      retrospective analysis of singleton pregnancies, the study group included
      patients with PPROM at 28-34 weeks' gestation and the control group included
      patients presented with spontaneous preterm delivery at 28-34 weeks' gestation.
      Both groups were subdivided according to gestational age - early (28-31 weeks'
      gestation) versus late (32-34 weeks' gestation). Adverse neonatal outcome
      included neonatal death, intraventricular haemorrhage grade 3/4, respiratory
      distress syndrome, periventricular leucomalacia and neonatal sepsis. The study
      and control groups included 94 and 86 women, respectively. The study group had a
      lower incidence of adverse neonatal outcome at the earlier weeks (28-31),
      compared with the control group at the same gestational age. In contrast, at 32
      34 weeks' gestation no difference in the risk for adverse neonatal outcome was
      noticed. Additionally, within the study group, chorioamnionitis rate was
      significantly higher among those who delivered at 32-34 weeks' gestation (p <
      0.01). No advantage for conservative management of PPROM was demonstrated beyond
      31 weeks' gestation. Moreover, conservative management of PPROM at 32-34 weeks'
      gestation may expose both mother and neonate to infectious morbidity. 

PMID- 25774538
TI  - The Role of T Helper 17 Cells and Other IL-17-Producing Cells in Bone Resorption
      and Remodeling.
AB  - In recent decades, many studies have highlighted the role of IL-17-producing
      cells in bone resorption. However, the importance of many IL-17-producing cell
      types remains largely unknown in bone remodeling. In this review, we summarize
      the function of IL-17-producing cells, with a focus on T helper 17 (Th17) cells,
      in bone resorption and remodeling. 

PMID- 25774539
TI  - Epidemiological Evaluation of Rubella Virus Infection among Pregnant Women in
      Ibadan, Nigeria.
AB  - Rubella is a vaccine-preventable, mild rash-inducing viral disease with
      complications that include a spectrum of birth defects in the developing fetus,
      especially if the infection is acquired in the early months of pregnancy.
      Consequently, the primary objective of global rubella control programs is
      prevention of congenital rubella infection and associated birth defects. Despite
      the availability of safe and effective vaccines, and the elimination of the
      rubella virus in many developed countries, substantial commitment to rubella
      control has not been demonstrated in developing countries. This study appraises
      immunity to rubella, and consequently makes appropriate recommendations aimed at
      facilitating effective control. A cross-sectional sero-surveillance study was
      carried out among defined 272 consenting ante-natal clinic attendees in south
      western, Nigeria. Prevalence rates of 91.54% and 1.84% were recorded for the anti
      rubella virus (anti-RV) IgG and IgM, respectively. Also, 90.7% and 92.3% of the
      women aged <=30 years and >30 years, respectively, had detectable anti-RV IgG. No
      significant association (p = 0.94) was recorded between anti-RV IgG detection and
      age of the women. Previous exposure and susceptibility of significant fraction of
      the population to rubella infection were confirmed. Considerable political
      commitment and promotion of free rubella immunization specifically for women with
      childbearing potential were recommended. 

PMID- 25774540
TI  - Suppressive properties of ginsenoside Rb2, a protopanaxadiol-type ginseng
      saponin, on reactive oxygen species and matrix metalloproteinase-2 in UV-B
      irradiated human dermal keratinocytes.
AB  - Ginsenosides, also known as ginseng saponins, are the principal bioactive
      ingredients of ginseng, which are responsible for its diverse pharmacological
      activities. The present work aimed to assess skin anti-photoaging properties of
      ginsenoside Rb2 (Rb2), one of the predominant protopanaxadiol-type ginsenosides,
      in human epidermal keratinocyte HaCaT cells under UV-B irradiation. When the
      cultured keratinocytes were subjected to Rb2 prior to UV-B irradiation, Rb2
      displayed suppressive activities on UV-B-induced reactive oxygen species
      elevation and matrix metalloproteinase-2 expression and secretion. However, Rb2
      at the used concentrations was unable to modulate cellular survivals in the UV-B
      irradiated keratinocytes. In brief, Rb2 possesses a protective role against the
      photoaging of human keratinocyte cells under UV-B irradiation. 

PMID- 25774542
TI  - Input-anticipating critical reservoirs show power law forgetting of unexpected
      input events.
AB  - Usually reservoir computing shows an exponential memory decay. This letter
      investigates under which circumstances echo state networks can show a power law
      forgetting. That means traces of earlier events can be found in the reservoir for
      very long time spans. Such a setting requires critical connectivity exactly at
      the limit of what is permissible according to the echo state condition. However,
      for general matrices, the limit cannot be determined exactly from theory. In
      addition, the behavior of the network is strongly influenced by the input flow.
      Results are presented that use certain types of restricted recurrent connectivity
      and anticipation learning with regard to the input, where power law forgetting
      can indeed be achieved. 

PMID- 25774541
TI  - A computationally efficient method for incorporating spike waveform information
      into decoding algorithms.
AB  - Spike-based brain-computer interfaces (BCIs) have the potential to restore motor
      ability to people with paralysis and amputation, and have shown impressive
      performance in the lab. To transition BCI devices from the lab to the clinic,
      decoding must proceed automatically and in real time, which prohibits the use of
      algorithms that are computationally intensive or require manual tweaking. A
      common choice is to avoid spike sorting and treat the signal on each electrode as
      if it came from a single neuron, which is fast, easy, and therefore desirable for
      clinical use. But this approach ignores the kinematic information provided by
      individual neurons recorded on the same electrode. The contribution of this
      letter is a linear decoding model that extracts kinematic information from
      individual neurons without spike-sorting the electrode signals. The method relies
      on modeling sample averages of waveform features as functions of kinematics,
      which is automatic and requires minimal data storage and computation. In offline
      reconstruction of arm trajectories of a nonhuman primate performing reaching
      tasks, the proposed method performs as well as decoders based on expertly
      manually and automatically sorted spikes. 

PMID- 25774543
TI  - Learning dynamics of a single polar variable complex-valued neuron.
AB  - This letter investigates the characteristics of the complex-valued neuron model
      with parameters represented by polar coordinates (called polar variable complex
      valued neuron). The parameters of the polar variable complex-valued neuron are
      unidentifiable. The plateau phenomenon can occur during learning of the polar
      variable complex-valued neuron. Furthermore, computer simulations suggest that a
      single polar variable complex-valued neuron has the following characteristics in
      the case of using the steepest gradient-descent method with square error: (1)
      unidentifiable parameters (singular points) degrade the learning speed and (2) a
      plateau can occur during learning. When the weight is attracted to the singular
      point, the learning tends to become stuck. However, computer simulations also
      show that the steepest gradient-descent method with amplitude-phase error and the
      complex-valued natural gradient method could reduce the effects of the singular
      points. The learning dynamics near singular points depends on the error functions
      and the training algorithms used. 

PMID- 25774544
TI  - Surrogate population models for large-scale neural simulations.
AB  - Because different parts of the brain have rich interconnections, it is not
      possible to model small parts realistically in isolation. However, it is also
      impractical to simulate large neural systems in detail. This article outlines a
      new approach to multiscale modeling of neural systems that involves constructing
      efficient surrogate models of populations. Given a population of neuron models
      with correlated activity and with specific, nonrandom connections, a surrogate
      model is constructed in order to approximate the aggregate outputs of the
      population. The surrogate model requires less computation than the neural model,
      but it has a clear and specific relationship with the neural model. For example,
      approximate spike rasters for specific neurons can be derived from a simulation
      of the surrogate model. This article deals specifically with neural engineering
      framework (NEF) circuits of leaky-integrate-and-fire point neurons. Weighted sums
      of spikes are modeled by interpolating over latent variables in the population
      activity, and linear filters operate on gaussian random variables to approximate
      spike-related fluctuations. It is found that the surrogate models can often
      closely approximate network behavior with orders-of-magnitude reduction in
      computational demands, although there are certain systematic differences between
      the spiking and surrogate models. Since individual spikes are not modeled, some
      simulations can be performed with much longer steps sizes (e.g., 20 ms). Possible
      extensions to non-NEF networks and to more complex neuron models are discussed. 

PMID- 25774545
TI  - FastMMD: Ensemble of Circular Discrepancy for Efficient Two-Sample Test.
AB  - The maximum mean discrepancy (MMD) is a recently proposed test statistic for the
      two-sample test. Its quadratic time complexity, however, greatly hampers its
      availability to large-scale applications. To accelerate the MMD calculation, in
      this study we propose an efficient method called FastMMD. The core idea of
      FastMMD is to equivalently transform the MMD with shift-invariant kernels into
      the amplitude expectation of a linear combination of sinusoid components based on
      Bochner's theorem and Fourier transform (Rahimi & Recht, 2007). Taking advantage
      of sampling the Fourier transform, FastMMD decreases the time complexity for MMD
      calculation from O(N(2)d) to O(LN d), where N and d are the size and dimension of
      the sample set, respectively. Here, L is the number of basis functions for
      approximating kernels that determines the approximation accuracy. For kernels
      that are spherically invariant, the computation can be further accelerated to
      O(LN log d) by using the Fastfood technique (Le, Sarlos, & Smola, 2013). The
      uniform convergence of our method has also been theoretically proved in both
      unbiased and biased estimates. We also provide a geometric explanation for our
      method, ensemble of circular discrepancy, which helps us understand the insight
      of MMD and we hope will lead to more extensive metrics for assessing the two
      sample test task. Experimental results substantiate that the accuracy of FastMMD
      is similar to that of MMD and with faster computation and lower variance than
      existing MMD approximation methods.

PMID- 25774546
TI  - Regulation of Local Ambient GABA Levels via Transporter-Mediated GABA Import and
      Export for Subliminal Learning.
AB  - Perception of supraliminal stimuli might in general be reflected in bursts of
      action potentials (spikes), and their memory traces could be formed through spike
      timing-dependent plasticity (STDP). Memory traces for subliminal stimuli might be
      formed in a different manner, because subliminal stimulation evokes a fraction
      (but not a burst) of spikes. Simulations of a cortical neural network model
      showed that a subliminal stimulus that was too brief (10 msec) to perceive
      transiently (more than about 500 msec) depolarized stimulus-relevant principal
      cells and hyperpolarized stimulus-irrelevant principal cells in a subthreshold
      manner. This led to a small increase or decrease in ongoing-spontaneous spiking
      activity frequency (less than 1 Hz). Synaptic modification based on STDP during
      this period effectively enhanced relevant synaptic weights, by which subliminal
      learning was improved. GABA transporters on GABAergic interneurons modulated
      local levels of ambient GABA. Ambient GABA molecules acted on extrasynaptic
      receptors, provided principal cells with tonic inhibitory currents, and
      contributed to achieving the subthreshold neuronal state. We suggest that ongoing
      spontaneous synaptic alteration through STDP following subliminal stimulation may
      be a possible neuronal mechanism for leaving its memory trace in cortical
      circuitry. Regulation of local ambient GABA levels by transporter-mediated GABA
      import and export may be crucial for subliminal learning.

PMID- 25774547
TI  - Repression of breast cancer cell growth by proteasome inhibitors in vitro: impact
      of mitogen-activated protein kinase phosphatase 1.
AB  - Mitogen activated protein kinase phosphatase-1 (MKP-1) has emerged as an
      important protein mediating breast cancer oncogenesis and chemoresistance to
      cancer chemotherapies, especially proteasome inhibitors. In this in vitro study,
      we utilized the breast cancer epithelial cell lines MCF-7 and MDA-MB-231, in
      comparison to MCF-10A control cells, to examine the impact of MKP-1 on breast
      cancer cell growth and repression by proteasome inhibitors. We confirm that
      proteasome inhibitors MG-132 and bortezomib induce MKP-1 protein upregulation and
      we show that one of the ways in which bortezomib increases MKP-1 in breast cancer
      cells, in addition to inhibition of ubiquitin-proteasome system, is via
      upregulation of MKP-1 mRNA expression in p38 MAPK-mediated manner. Notably, these
      effects are specific to cancer cells, as bortezomib activated p38 MAPK and
      induced MKP-1 in MCF-7 and MDA-MB-231 breast cancer cells, but not in control
      cells (MCF-10A). We took a dual approach toward targeting MKP-1 to show that
      bortezomib-induced effects are enhanced. Firstly, treatment with the non-specific
      MKP-1 inhibitor triptolide reduces breast cancer cell growth and augments
      proteasome inhibitor-induced effects. Secondly, specific knock-down of MKP-1 with
      siRNA significantly repressed cell viability by reduced cyclin D1 expression, and
      enhanced repression of cancer cell growth by proteasome inhibitors. Taken
      together, these results indicate that removing the unwanted (MKP-1-inducing)
      effects of bortezomib significantly improves the efficacy of proteasome
      inhibition in breast cancer cells. Thus, future development of drugs targeting
      MKP-1 offer promise of combination therapies with reduced toxicity and enhanced
      cell death in breast cancer. 

PMID- 25774548
TI  - The Relationship between Mood Instability and Suicidal Thoughts.
AB  - The objective of this study was to determine whether affective instability
      predicts suicidal thoughts. Data from a Dutch panel study (N = 1686) was used.
      Affective instability was assessed with 7 items representing suddenly shifting
      moods. Suicidal thoughts were assessed by the occurrence of suicidal thoughts in
      the past week. Negative affect was indexed by anxious, depressed and angry moods
      extracted by factor analysis. Odds ratios using logistic regression modeling were
      calculated, adjusting for clinical and demographic variables. The study found
      that both males (OR: 1.14; 95% CI: 1.02-1.28) and females (OR: 1.11; 95% CI: 1.00
      1.23) were more likely to experience suicidal thinking with higher affective
      instability. Affective instability and negative affect independently predict
      suicidal thoughts. Affective instability requires more attention in the
      assessment of suicide risk.

PMID- 25774549
TI  - Unique and Shared Metabolic Regulation in Clonal beta-Cells and Primary Islets
      Derived From Rat Revealed by Metabolomics Analysis.
AB  - As models for beta-cell metabolism, rat islets are, to some extent, a,
      heterogeneous cell population stressed by the islet isolation procedure, whereas
      rat-derived clonal beta-cells exhibit a tumor-like phenotype. To describe to what
      extent either of these models reflect normal cellular metabolism, we compared
      metabolite profiles and gene expression in rat islets and the INS-1 832/13 line,
      a widely used clonal beta-cell model. We found that insulin secretion and
      metabolic regulation provoked by glucose were qualitatively similar in these beta
      cell models. However, rat islets exhibited a more pronounced glucose-provoked
      increase of glutamate, glycerol-3-phosphate, succinate, and lactate levels,
      whereas INS-1 832/13 cells showed a higher glucose-elicited increase in glucose-6
      phosphate, alanine, isocitrate, and alpha-ketoglutarate levels. Glucose induced a
      decrease in levels of gamma-aminobutyrate (GABA) and aspartate in rat islets and
      INS-1 832/13 cells, respectively. Genes with cellular functions related to
      proliferation and the cell cycle were more highly expressed in the INS-1 832/13
      cells. Most metabolic pathways that were differentially expressed included GABA
      metabolism, in line with altered glucose responsiveness of GABA. Also, lactate
      dehydrogenase A, which is normally expressed at low levels in mature beta-cells,
      was more abundant in rat islets than in INS-1 832/13 cells, confirming the
      finding of elevated glucose-provoked lactate production in the rat islets.
      Overall, our results suggest that metabolism in rat islets and INS-1 832/13 cells
      is qualitatively similar, albeit with quantitative differences. Differences may
      be accounted for by cellular heterogeneity of islets and proliferation of the INS
      1 832/13 cells. 

PMID- 25774550
TI  - The effects of short-term and long-term testosterone supplementation on blood
      viscosity and erythrocyte deformability in healthy adult mice.
AB  - Testosterone treatment induces erythrocytosis that could potentially affect blood
      viscosity and cardiovascular risk. We thus investigated the effects of
      testosterone administration on blood viscosity and erythrocyte deformability
      using mouse models. Blood viscosity, erythrocyte deformability, and hematocrits
      were measured in normal male and female mice, as well as in females and castrated
      males after short-term (2 wk) and long-term (5-7 mo) testosterone intervention
      (50 mg/kg, weekly). Castrated males for long-term intervention were studied in
      parallel with the normal males to assess the effect of long-term testosterone
      deprivation. An additional short-term intervention study was conducted in females
      with a lower testosterone dose (5 mg/kg). Our results indicate no rheological
      difference among normal males, females, and castrated males at steady-state.
      Short-term high-dose testosterone increased hematocrit and whole-blood viscosity
      in both females and castrated males. This effect diminished after long-term
      treatment, in association with increased erythrocyte deformability in the
      testosterone-treated mice, suggesting the presence of adaptive mechanism.
      Considering that cardiovascular events in human trials are seen early after
      intervention, rheological changes as potential mediator of vascular events
      warrant further investigation. 

PMID- 25774551
TI  - Activation of transient receptor potential vanilloid 3 channel suppresses
      adipogenesis.
AB  - The present study shows that activation of the transient receptor potential
      vanilloid 3 channel (TRPV3) suppresses adipocyte differentiation. We also found
      that a major functional catechin compound in green tea and cocoa, (-)
      epicatechin, exerts antiadipogenic effects in the adipocytes through direct
      activation of TRPV3. TRPV3 was detected in the 3T3-L1 adipocytes using
      immunohistochemistry and semiquantitative PCR. TRPV3 activation by activators (-)
      epicatechin and diphenylborinic anhydride was determined using live cell
      fluorescent Ca(2+) imaging and patch-clamp electrophysiology. Using RNA
      interference, immunoblotting, and Oil red O staining, we found that the TRPV3
      agonists prevented adipogenesis by inhibiting the phosphorylation of insulin
      receptor substrate 1, the downstream phosphoinositide 3-kinase/Akt/forkhead box
      protein O1 axis, and the expression of the adipogenic genes peroxisome
      proliferator-activated receptor gamma and CCAAT/enhancer-binding protein alpha.
      TRPV3 overexpression hindered adipogenesis in the 3T3-L1 cells. In vivo studies
      showed that chronic treatment with the TRPV3 activators prevented adipogenesis
      and weight gain in the mice fed on high-fat diets. Moreover, TRPV3 expression was
      reduced in the visceral adipose tissue from mice fed on high-fat diets and obese
      (ob/ob) and diabetic (db/m(+)) mice. In conclusion, our study illustrates the
      antiadipogenic role of TRPV3 in the adipocytes. 

PMID- 25774552
TI  - FSP-1 Impairs the Function of Endothelium Leading to Failure of Arteriovenous
      Grafts in Diabetic Mice.
AB  - To understand how endothelial cell (EC) dysfunction contributes to the failure of
      arteriovenous graft (AVG), we investigated the role of fibroblast-specific
      protein 1 (FSP-1) in cultured ECs and a mouse AVG model. In vitro, we uncovered a
      new FSP-1-dependent pathway that activates rho-associated, coiled-coil-containing
      protein kinase 1 (ROCK1) in ECs, leading to phosphorylation of myosin light chain
      2 resulting in EC dysfunction. In cultured ECs, high glucose stimulated FSP-1
      expression and increased permeability of an EC monolayer. The increase in
      permeability by the high glucose concentration was mediated by FSP-1 expression.
      Treatment of cultured ECs with FSP-1 caused leakage of the endothelial barrier
      plus increased expression of adhesion molecules and decreased expression of
      junction molecules. These responses were initiated by binding of FSP-1 to
      receptor for advanced glycation end products, which resulted in ROCK1 activation.
      In vivo, diabetes increased infiltration of inflammatory cells into AVGs and
      stimulated neointima formation. Increased FSP-1 expression and ROCK1 activation
      were found in AVGs of diabetic mice. Blocking FSP-1 suppressed diabetes-induced
      ROCK1 activation in AVGs. In mice with FSP-1 knockout or with ROCK1 knockout,
      accumulation of inflammatory cells and neointima formation in AVG were attenuated
      despite diabetes. Thus, mechanisms of inhibiting FSP-1 in ECs could improve AVG
      function. 

PMID- 25774553
TI  - Naringenin prevents obesity, hepatic steatosis, and glucose intolerance in male
      mice independent of fibroblast growth factor 21.
AB  - The molecular mechanisms and metabolic pathways whereby the citrus flavonoid,
      naringenin, reduces dyslipidemia and improves glucose tolerance were investigated
      in C57BL6/J wild-type mice and fibroblast growth factor 21 (FGF21) null (Fgf21(-/
      )) mice. FGF21 regulates energy homeostasis and the metabolic adaptation to
      fasting. One avenue of this regulation is through induction of peroxisome
      proliferator-activated receptor-gamma coactivator-1alpha (Pgc1a), a regulator of
      hepatic fatty acid oxidation and ketogenesis. Because naringenin is a potent
      activator of hepatic FA oxidation, we hypothesized that induction of FGF21 might
      be an integral part of naringenin's mechanism of action. Furthermore, we
      predicted that FGF21 deficiency would potentiate high-fat diet (HFD)-induced
      metabolic dysregulation and compromise metabolic protection by naringenin. The
      absence of FGF21 exacerbated the response to a HFD. Interestingly, naringenin
      supplementation to the HFD robustly prevented obesity in both genotypes. Gene
      expression analysis suggested that naringenin was not primarily targeting fatty
      acid metabolism in white adipose tissue. Naringenin corrected hepatic
      triglyceride concentrations and normalized hepatic expression of Pgc1a, Cpt1a,
      and Srebf1c in both wild-type and Fgf21(-/-) mice. HFD-fed Fgf21(-/-) mice
      displayed greater muscle triglyceride deposition, hyperinsulinemia, and impaired
      glucose tolerance as compared with wild-type mice, confirming the role of FGF21
      in insulin sensitivity; however, naringenin supplementation improved these
      metabolic parameters in both genotypes. We conclude that FGF21 deficiency
      exacerbates HFD-induced obesity, hepatic steatosis, and insulin resistance.
      Furthermore, FGF21 is not required for naringenin to protect mice from HFD
      induced metabolic dysregulation. Collectively these studies support the concept
      that naringenin has potent lipid-lowering effects and may act as an insulin
      sensitizer in vivo. 

PMID- 25774554
TI  - Vitamin d deficiency attenuates high-fat diet-induced hyperinsulinemia and
      hepatic lipid accumulation in male mice.
AB  - It is increasingly recognized that vitamin D deficiency is associated with
      increased risks of metabolic disorders among overweight children. A recent study
      showed that vitamin D deficiency exacerbated inflammation in nonalcoholic fatty
      liver disease through activating toll-like receptor 4 in a high-fat diet (HFD)
      rat model. The present study aimed to further investigate the effects of vitamin
      D deficiency on HFD-induced insulin resistance and hepatic lipid accumulation.
      Male ICR mice (35 d old) were randomly assigned into 4 groups as follows. In
      control diet and vitamin D deficiency diet (VDD) groups, mice were fed with
      purified diets. In HFD and VDD+HFD groups, mice were fed with HFD. In VDD and
      VDD+HFD groups, vitamin D in feed was depleted. Feeding mice with vitamin D
      deficiency diet did not induce obesity, insulin resistance, and hepatic lipid
      accumulation. By contrary, vitamin D deficiency markedly alleviated HFD-induced
      overweight, hyperinsulinemia, and hepatic lipid accumulation. Moreover, vitamin D
      deficiency significantly attenuated HFD-induced up-regulation of hepatic
      peroxisome proliferator-activated receptor gamma, which promoted hepatic lipid
      uptake and lipid droplet formation, and its target gene cluster of
      differentiation 36. In addition, vitamin D deficiency up-regulated carnitine
      palmitoyltrans 2, the key enzyme for fatty acid beta-oxidation, and uncoupling
      protein 3, which separated oxidative phosphorylation from ATP production, in
      adipose tissue. These data suggest that vitamin D deficiency is not a direct risk
      factor for obesity, insulin resistance, and hepatic lipid accumulation. Vitamin D
      deficiency alleviates HFD-induced overweight, hyperinsulinemia, and hepatic lipid
      accumulation through promoting fatty acid beta-oxidation and elevating energy
      expenditure in adipose tissue. 

PMID- 25774555
TI  - The Flower Tea Coreopsis tinctoria Increases Insulin Sensitivity and Regulates
      Hepatic Metabolism in Rats Fed a High-Fat Diet.
AB  - An infusion of Coreopsis tinctoria (CT) flowering tops is traditionally used in
      Portugal to control hyperglycemia; however, the effects of CT protection against
      high-fat diet (HFD)-induced hepatic insulin resistance have not been
      systematically studied and the precise mechanism of action is not clear. The
      metabolomic profiles of insulin-resistant rats fed a HFD and a CT-supplemented
      diet (HFD supplemented with CT drinking) for 8 weeks were investigated. Serum
      samples for clinical biochemistry and liver samples for histopathology and liquid
      chromatography-mass spectrometry-based metabolomic research were collected.
      Western blot and quantitative real-time PCR analyses were further used to measure
      the expression of several relevant enzymes together with perturbed metabolic
      pathways. Using analysis software, the CT treatment was found to significantly
      ameliorate the disturbance in 10 metabolic pathways. Combined metabolomic,
      Western blot, and quantitative real-time PCR analyses revealed that CT treatment
      significantly improved the glucose homeostasis by, on the one hand, through
      inhibiting the expression of gluconeogenic pathway key proteins glucose-6
      phosphatase and phosphoenolpyruvate carboxykinase and, on the other hand, via
      regulating the mRNA or protein levels of the Krebs cycle critical enzymes
      (citrate synthase, succinate dehydrogenase complex, subunit A, flavoprotein, and
      dihydrolipoamide S-succinyltransferase). These results provide metabolic evidence
      of the complex pathogenic mechanism involved in hepatic insulin resistance and
      that the supplementation with CT improves insulin resistance at a global scale.
      Liquid chromatography-mass spectrometry-based metabolomics approaches are helpful
      to further understand diabetes-related mechanisms. 

PMID- 25774557
TI  - Present status of clinical care for postpartum patients with hypertensive
      disorders of pregnancy in Japan: findings from a nationwide questionnaire survey.
AB  - OBJECTIVE: To assess the present status of clinical care for postpartum patients
      with hypertensive disorders of pregnancy (HDP) in Japan. METHODS: We conducted a
      nationwide questionnaire survey of obstetricians, internists and hypertension
      specialists and analyzed 686 valid responses. RESULTS: Though HDP is widely known
      as a risk factor for subsequent hypertension and cardiovascular disease, over one
      third of obstetricians terminated their postpartum follow-up of HDP patients
      without referring them to other departments. CONCLUSION: It is important to
      establish an effective referral system, whereby patients with HDP can be smoothly
      transferred to primary care or a specialist physician after childbirth for long
      term monitoring and management of blood pressure.

PMID- 25774556
TI  - A Novel Population of Inner Cortical Cells in the Adrenal Gland That Displays
      Sexually Dimorphic Expression of Thyroid Hormone Receptor-beta1.
AB  - The development of the adrenal cortex involves the formation and then subsequent
      regression of immature or fetal inner cell layers as the mature steroidogenic
      outer layers expand. However, controls over this remodeling, especially in the
      immature inner layer, are incompletely understood. Here we identify an inner
      cortical cell population that expresses thyroid hormone receptor-beta1 (TRbeta1),
      one of two receptor isoforms encoded by the Thrb gene. Using mice with a Thrb(b1)
      reporter allele that expresses lacZ instead of TRbeta1, beta-galactosidase was
      detected in the inner cortex from early stages. Expression peaked at juvenile
      ages in an inner zone that included cells expressing 20-alpha-hydroxysteroid
      dehydrogenase, a marker of the transient, so-called X-zone in mice. The beta
      galactosidase-positive zone displayed sexually dimorphic regression in males
      after approximately 4 weeks of age but persisted in females into adulthood in
      either nulliparous or parous states. T3 treatment promoted hypertrophy of inner
      cortical cells, induced some markers of mature cortical cells, and, in males,
      delayed the regression of the TRbeta1-positive zone, suggesting that TRbeta1
      could partly divert the differentiation fate and counteract male-specific
      regression of inner zone cells. TRbeta1-deficient mice were resistant to these
      actions of T3, supporting a functional role for TRbeta1 in the inner cortex. 

PMID- 25774558
TI  - Distinct Trajectories of Physical Activity Among Patients with COPD During and
      After Pulmonary Rehabilitation.
AB  - Little is known about longitudinal trends in objectively measured physical
      activity (PA) during and after pulmonary rehabilitation (PR) for individuals with
      Chronic Obstructive Pulmonary Disease (COPD). The purpose of this study was to
      examine the PA trajectories of patients with COPD during and after PR and whether
      demographic, clinical, or program characteristics differed across these
      trajectories. The study was approved by Research Ethics Boards at all
      participating institutions, and written informed consent was obtained from each
      participant prior to study inclusion. COPD patients (N = 190) completed a
      questionnaire and wore a pedometer for 7 days at baseline, end of PR, and 3 and 9
      months after completing PR. Latent class growth analyses showed that two distinct
      PA trajectories emerged. Active Maintainers averaged 9177 steps/day at baseline,
      and maintained this level throughout the assessment and post rehabilitation
      period. In contrast, Inactive Maintainers averaged 3133 steps/day at baseline,
      which also remained stable during and after PR. Follow-up analyses showed the
      Inactive Maintainers were more likely to be retired from work and have lower
      baseline scores for their stress tests and 6-minute walk tests compared to Active
      Maintainers (all p < 0.05). These results suggest that two distinct steps/day
      trajectories exist for COPD patients during and after completing PR that are
      partially explained by specific demographic and clinical characteristics.

PMID- 25774559
TI  - Improving medication adherence in rheumatoid arthritis (RA): a pilot study.
AB  - The aim of this exploratory pilot study was to adapt a psychological intervention
      to improve adherence to medication for patients with rheumatoid arthritis (RA).
      The approach draws on cognitive behavioural therapy (CBT) techniques, including
      motivational interviewing . The current study aimed to (i) adapt the intervention
      for patients with RA, (ii) assess its effectiveness in improving adherence to
      medication and (iii) evaluate patients' experience of the intervention.
      Participants were randomly allocated to either the 'intervention group' (N  = 
      10), receiving up to six weekly sessions of 'Compliance Therapy', or to the 'wait
      list control' group (N  =  8), who received standard care. Data was collected pre
      intervention (baseline), post intervention and at six weeks post intervention
      (follow-up). Eighteen female participants with a mean age of 48.78 years (SD
      15.12) took part in the study. Comparisons across the two time points for each
      group found that only those in the 'intervention' group demonstrated significant
      improvement in mean scores on adherence measures. Between-group comparisons were
      not significant. The pilot study suggests that an intervention based on CBT may
      improve adherence in patients with RA, but further research is required.

PMID- 25774560
TI  - Antiproliferative effect of isolated isoquinoline alkaloid from Mucuna pruriens
      seeds in hepatic carcinoma cells.
AB  - The present study was undertaken to investigate the antiproliferative action of
      isolated M1 (6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid) from
      Mucuna pruriens seeds using human hepatic carcinoma cell line (Huh-7 cells).
      Initially, docking studies was performed to find out the binding affinities of M1
      to caspase-3 and 8 enzymes. Later, cytotoxic action of M1 was measured by cell
      growth inhibition (MTT), followed by caspase-3 and 8 enzymes assay
      colorimetrically. Our results collectively suggested that M1 had strong binding
      affinity to caspase-8 in molecular modelling. M1 possessed antiproliferative
      activity on Huh-7 cells (EC50 = 13.97 MUM) and also inhibited the action of
      caspase-8 enzyme, signified process of apoptosis. M1 was active against Huh-7
      cells that may be useful for future hepatic cancer treatment.

PMID- 25774561
TI  - Individual and contextual determinants of adequate maternal health care services
      in Kenya.
AB  - This study aimed to examine individual and community level factors associated
      with adequate use of maternal antenatal health services in Kenya. Individual and
      community level factors associated with adequate use of maternal health care
      (MHC) services were obtained from the 2008-09 Kenya Demographic and Health Survey
      data set. Multilevel partial-proportional odds logit models were fitted using
      STATA 13.0 to quantify the relations of the selected covariates to adequate MHC
      use, defined as a three-category ordinal variable. The sample consisted of 3,621
      women who had at least one live birth in the five-year period preceding this
      survey. Only 18 percent of the women had adequate use of MHC services. Greater
      educational attainment by the woman or her partner, higher socioeconomic status,
      access to medical insurance coverage, and greater media exposure were the
      individual-level factors associated with adequate use of MHC services. Greater
      community ethnic diversity, higher community-level socioeconomic status, and
      greater community-level health facility deliveries were the contextual-level
      factors associated with adequate use of MHC. To improve the use of MHC services
      in Kenya, the government needs to design and implement programs that target
      underlying individual and community level factors, providing focused and
      sustained health education to promote the use of antenatal, delivery, and
      postnatal care. 

PMID- 25774562
TI  - Reduced auditory evoked gamma band response and cognitive processing deficits in
      first episode schizophrenia.
AB  - OBJECTIVES: Gamma-band oscillations (e.g., the early auditory evoked gamma-band
      response, aeGBR) have been suggested to mediate cognitive and perceptual
      processes by driving the synchronization of local neuronal populations. Reduced
      aeGBR is a consistent finding in patients with schizophrenia and high-risk
      subjects, and has been proposed to represent an endophenotype for the illness.
      However, it is still unclear whether this reduction represents a deficit in
      sensory or cognitive processes, or a combination of the two. The present study
      investigated this question by manipulating the difficulty of an auditory reaction
      task in patients with first-episode schizophrenia and healthy controls. METHODS:
      A 64-channel EEG was recorded in 23 patients with first-episode schizophrenia and
      22 healthy controls during two conditions of an auditory reaction task: an easy
      condition that merely required low-level vigilance, and a difficult condition
      that placed significant demands on attention and working memory. RESULTS: In
      contrast to healthy controls, patients failed to increase aeGBR power and phase
      locking in the difficult condition. In patients, aeGBR power and phase-locking
      indices were associated with working memory deficits. CONCLUSIONS: The observed
      results confirm the applicability of aeGBR disturbances as a stable endophenotype
      of schizophrenia, and suggest a cognitive, rather than sensory, deficit at their
      origin.

PMID- 25774563
TI  - Seroprevalence of anti-Toxoplasma gondii and anti-Borrelia species antibodies in
      patients with schizophrenia: a case-control study from western Turkey.
AB  - OBJECTIVES: We examined IgG antibody seroprevalence and risk factors for anti
      Toxoplasma gondii and anti-Borrelia sp. in schizophrenic patients. METHODS: This
      case-control study included 30 schizophrenic patients and 60 healthy individuals.
      Serological analyses were identified by using ELISA technique. RESULTS: In the
      case group the Toxoplasma seropositivity was 33.3% and Borrelia seropositivity
      was 13.3%, while in the control group the Toxoplasma positivity was 21.7% and
      Borrelia seropositivity was 15.0%. There was no significant difference with
      regard to seroprevalence between the groups (P = 0.232; P = 0.832, respectively).
      There was statistically significant difference between case and control groups
      related to hand and kitchen utensil hygiene after dealing with raw meat (P =
      0.001). CONCLUSIONS: Our data showed the rate of Toxoplasma antibodies was higher
      in the case group, while the rate of Borrelia antibodies was higher in the
      control group. In both groups the high rates of seropositivity for Toxoplasma
      gondii and Borrelia sp. is thought to be due to neglect of personal hygiene. The
      present study also is the first to examine the association between Borrelia sp.
      and schizophrenia. Further studies are needed to determine whether there is an
      association between Borrelia sp. and schizophrenia or not.

PMID- 25774564
TI  - Understanding the Structure-Function Relationship of Lysozyme Resistance in
      Staphylococcus aureus by Peptidoglycan O-Acetylation Using Molecular Docking,
      Dynamics, and Lysis Assay.
AB  - Lysozyme is an important component of the host innate defense system. It cleaves
      the beta-1,4 glycosidic bonds between N-acetylmuramic acid and N
      acetylglucosamine of bacterial peptidoglycan and induce bacterial lysis.
      Staphylococcus aureus (S. aureus), an opportunistic commensal pathogen, is highly
      resistant to lysozyme, because of the O-acetylation of peptidoglycan by O-acetyl
      transferase (oatA). To understand the structure-function relationship of lysozyme
      resistance in S. aureus by peptidoglycan O-acetylation, we adapted an integrated
      approach to (i) understand the effect of lysozyme on the growth of S. aureus
      parental and the oatA mutant strain, (ii) study the lysozyme induced lysis of
      exponentially grown and stationary phase of both the S. aureus parental and oatA
      mutant strain, (iii) investigate the dynamic interaction mechanism between normal
      (de-O-acetylated) and O-acetylated peptidoglycan substrate in complex with
      lysozyme using molecular docking and molecular dynamics simulations, and (iv)
      quantify lysozyme resistance of S. aureus parental and the oatA mutant in
      different human biological fluids. The results indicated for the first time that
      the active site cleft of lysozyme binding with O-acetylated peptidoglycan in S.
      aureus was sterically hindered and the structural stability was higher for the
      lysozyme in complex with normal peptidoglycan. This could have conferred reduced
      survival of the S. aureus oatA mutant in different human biological fluids.
      Consistent with this computational analysis, the experimental data confirmed
      decrease in the growth, lysozyme induced lysis, and lysozyme resistance, due to
      peptidoglycan O-acetylation in S. aureus. 

PMID- 25774565
TI  - Electronic signatures of a model pollutant-particle system: chemisorbed phenol on
      TiO2(110).
AB  - Environmentally persistent free radicals (EPFRs) are a class of composite
      organic/metal oxide pollutants that have recently been discovered to form from a
      wide variety of substituted benzenes chemisorbed to commonly encountered oxides.
      Although a qualitative understanding of EPFR formation on particulate metal
      oxides has been achieved, a detailed understanding of the charge transfer
      mechanism that must accompany the creation of an unpaired radical electron is
      lacking. In this study, we perform photoelectron spectroscopy and electron energy
      loss spectroscopy on a well-defined model system-phenol chemisorbed on TiO2(110)
      to directly observe changes in the electronic structure of the oxide and
      chemisorbed phenol as a function of adsorption temperature. We show strong
      evidence that, upon exposure at high temperature, empty states in the TiO2 are
      filled and the phenol HOMO is depopulated, as has been proposed in a conceptual
      model of EPFR formation. This experimental evidence of charge transfer provides a
      deeper understanding of the EPFR formation mechanism to guide future experimental
      and computational studies as well as potential environmental remediation
      strategies. 

PMID- 25774566
TI  - Amantadine Effect on Perceptions of Irritability after Traumatic Brain Injury:
      Results of the Amantadine Irritability Multisite Study.
AB  - This study examines the effect of amantadine on irritability in persons in the
      post-acute period after traumatic brain injury (TBI). There were 168 persons >=6
      months post-TBI with irritability who were enrolled in a parallel-group,
      randomized, double-blind, placebo-controlled trial receiving either amantadine
      100 mg twice daily or equivalent placebo for 60 days. Subjects were assessed at
      baseline and days 28 (primary end-point) and 60 of treatment using observer-rated
      and participant-rated Neuropsychiatric Inventory (NPI-I) Most Problematic item
      (primary outcome), NPI Most Aberrant item, and NPI-I Distress Scores, as well as
      physician-rated Clinical Global Impressions (CGI) scale. Observer ratings between
      the two groups were not statistically significantly different at day 28 or 60;
      however, observers rated the majority in both groups as having improved at both
      intervals. Participant ratings for day 60 demonstrated improvements in both
      groups with greater improvement in the amantadine group on NPI-I Most Problematic
      (p<0.04) and NPI-I Distress (p<0.04). These results were not significant with
      correction for multiple comparisons. CGI demonstrated greater improvement for
      amantadine than the placebo group (p<0.04). Adverse event occurrence did not
      differ between the two groups. While observers in both groups reported large
      improvements, significant group differences were not found for the primary
      outcome (observer ratings) at either day 28 or 60. This large placebo or
      nonspecific effect may have masked detection of a treatment effect. The result of
      this study of amantadine 100 mg every morning and noon to reduce irritability was
      not positive from the observer perspective, although there are indications of
      improvement at day 60 from the perspective of persons with TBI and clinicians
      that may warrant further investigation. 

PMID- 25774567
TI  - Reactivity and selectivity patterns in hydrogen atom transfer from amino acid C-H
      bonds to the cumyloxyl radical: polar effects as a rationale for the preferential
      reaction at proline residues.
AB  - Absolute rate constants for hydrogen atom transfer (HAT) from the C-H bonds of N
      Boc-protected amino acids to the cumyloxyl radical (CumO(*)) were measured by
      laser flash photolysis. With glycine, alanine, valine, norvaline, and tert
      leucine, HAT occurs from the alpha-C-H bonds, and the stability of the alpha
      carbon radical product plays a negligible role. With leucine, HAT from the alpha-
      and gamma-C-H bonds was observed. The higher kH value measured for proline was
      explained in terms of polar effects, with HAT that predominantly occurs from the
      delta-C-H bonds, providing a rationale for the previous observation that proline
      residues represent favored HAT sites in the reactions of peptides and proteins
      with (*)OH. Preferential HAT from proline was also observed in the reactions of
      CumO(*) with the dipeptides N-BocProGlyOH and N-BocGlyGlyOH. The rate constants
      measured for CumO(*) were compared with the relative rates obtained previously
      for the corresponding reactions of different hydrogen-abstracting species. The
      behavior of CumO(*) falls between those observed for the highly reactive radicals
      Cl(*) and (*)OH and the significantly more stable Br(*). Taken together, these
      results provide a general framework for the description of the factors that
      govern reactivity and selectivity patterns in HAT reactions from amino acid C-H
      bonds. 

PMID- 25774568
TI  - Acceptability of non-abstinence goals among students enrolled in addiction
      studies programs across the United States.
AB  - BACKGROUND: Previous studies of acceptability of non-abstinence recruited older,
      experienced addiction professionals; it's possible that younger, emerging
      addiction professionals may be more accepting of non-abstinence, perhaps due to
      training in harm reduction. METHODS: One hundred seventy graduate and
      undergraduate students enrolled in college/university-based programs offering
      training in addiction studies across the United States were recruited to complete
      a Web-based questionnaire assessing whether acceptability of non-abstinence
      outcome goals varied depending on the specific substance a client consumes,
      severity of diagnosis, and finality of outcome goal. RESULTS: More respondents
      rated non-abstinence an acceptable Intermediate goal for clients diagnosed with a
      Moderate cannabis use disorder (57%) or Moderate alcohol use disorder (45%) than
      for clients diagnosed with any other listed Moderate substance use disorder (32%
      to 36%). Similarly, larger proportions of respondents rated non-abstinence an
      acceptable Final goal for clients diagnosed with a Moderate cannabis use disorder
      (37%) or Moderate alcohol use disorder (31%) than for clients diagnosed with any
      other listed Moderate substance use disorder (19% to 23%). Only 14% to 26% of
      respondents rated non-abstinence an acceptable Final goal for clients diagnosed
      with a Severe substance use disorder, but 28% to 42% rated non-abstinence
      acceptable for clients diagnosed with a Severe substance use disorder when non
      abstinence was an Intermediate goal. CONCLUSIONS: Compared with previous research
      examining the acceptability of non-abstinence, these results suggest that
      students enrolled in addiction studies training programs may be more accepting of
      clients who decide to pursue non-abstinence either as an intermediate step on the
      way to abstinence or as a final goal.

PMID- 25774569
TI  - Job embeddedness: a multifoci theoretical extension.
AB  - Integrating the expanding job embeddedness (JE) literature, in this article we
      advance a multifoci model of JE that is theoretically grounded in conservation of
      resources (COR) theory. From COR theory, we posit that employees' motivation to
      acquire and protect resources explains why they become embedded and how they
      behave once embedded. Our COR-based JE model highlights contextual antecedents
      that clarify how employees become embedded within different foci. Its multifoci
      theoretical lens also illustrates how different forms of work-focused
      embeddedness differentially affect work outcomes and how they interact with
      nonwork foci to influence those outcomes. Along with directions for further
      research, we further discuss theoretical and practical implications of our
      integrative formulation.

PMID- 25774570
TI  - Only time will tell: the changing relationships between LMX, job performance, and
      justice.
AB  - Although it has been argued that leader-member exchange (LMX) is a phenomenon
      that develops over time, the existing LMX literature is largely cross-sectional
      in nature. Yet, there is a great need for unraveling how LMX develops over time.
      To address this issue in the LMX literature, we examine the relationships of LMX
      with 2 variables known for changing over time: job performance and justice
      perceptions. On the basis of current empirical findings, a simulation deductively
      shows that LMX develops over time, but differently in early stages versus more
      mature stages. Our findings also indicate that performance and justice trends
      affect LMX. Implications for LMX theory and for longitudinal research on LMX,
      performance, and justice are discussed. (PsycINFO Database Record

PMID- 25774571
TI  - Fostering employee service creativity: Joint effects of customer empowering
      behaviors and supervisory empowering leadership.
AB  - Integrating insights from the literature on customers' central role in service
      and the literature on employee creativity, we offer theoretical and empirical
      account of how and when customer empowering behaviors can motivate employee
      creativity during service encounters and, subsequently, influence customer
      satisfaction with service experience. Using multilevel, multisource, experience
      sampling data from 380 hairstylists matched with 3550 customers in 118 hair
      salons, we found that customer empowering behaviors were positively related to
      employee creativity and subsequent customer satisfaction via employee state
      promotion focus. Results also showed that empowering behaviors from different
      agents function synergistically in shaping employee creativity: supervisory
      empowering leadership strengthened the indirect effect of customer empowering
      behaviors on employee creativity via state promotion focus.

PMID- 25774572
TI  - Global Uncertainty Propagation and Sensitivity Analysis in the CH3OCH2 + O2
      System: Combining Experiment and Theory To Constrain Key Rate Coefficients in DME
      Combustion.
AB  - Statistical rate theory calculations, in particular formulations of the chemical
      master equation, are widely used to calculate rate coefficients of interest in
      combustion environments as a function of temperature and pressure. However,
      despite the increasing accuracy of electronic structure calculations, small
      uncertainties in the input parameters for these master equation models can lead
      to relatively large uncertainties in the calculated rate coefficients. Master
      equation input parameters may be constrained further by using experimental data
      and the relationship between experiment and theory warrants further
      investigation. In this work, the CH3OCH2 + O2 system, of relevance to the
      combustion of dimethyl ether (DME), is used as an example and the input
      parameters for master equation calculations on this system are refined through
      fitting to experimental data. Complementing these fitting calculations, global
      sensitivity analysis is used to explore which input parameters are constrained by
      which experimental conditions, and which parameters need to be further
      constrained to accurately predict key elementary rate coefficients. Finally,
      uncertainties in the calculated rate coefficients are obtained using both
      correlated and uncorrelated distributions of input parameters. 

PMID- 25774573
TI  - Antiphase dual-color correlation in a reactant-product pair imparts
      ultrasensitivity in reaction-linked double-photoswitching fluorescence imaging.
AB  - A pair of reversible photochemical reactions correlates their reactant and
      product specifically, and such a correlation uniquely distinguishes their
      correlated signal from others that are not linked by this reversible reaction.
      Here a nanoparticle-shielded fluorophore is photodriven to undergo structural
      dynamics, alternating between a green-fluorescence state and a red-fluorescence
      state. As time elapses, the fluorophore can be in either state but not both at
      the same time. Thus, the red fluorescence is maximized while the green
      fluorescence is minimized and vice versa. Such an antiphase dual-color (AD)
      corelationship between the red and green fluorescence maxima as well as between
      their minima can be exploited to greatly improve the signal-to-noise ratio, thus
      enhancing the ultimate detection limit. Potential benefits of this correlation
      include elimination of all interferences originating from single-color dyes and
      signal amplification of AD photoswitching molecules by orders of magnitude. 

PMID- 25774574
TI  - ZnO-based thin film transistors employing aluminum titanate gate dielectrics
      deposited by spray pyrolysis at ambient air.
AB  - The replacement of SiO2 gate dielectrics with metal oxides of higher dielectric
      constant has led to the investigation of a wide range of materials with superior
      properties compared with SiO2. Despite their attractive properties, these high-k
      dielectrics are usually manufactured using costly vacuum-based techniques. To
      overcome this bottleneck, research has focused on the development of alternative
      deposition methods based on solution-processable metal oxides. Here we report the
      application of spray pyrolysis for the deposition and investigation of Al2x
      1.TixOy dielectrics as a function of the [Ti(4+)]/[Ti(4+)+2.Al(3+)] ratio and
      their implementation in thin film transistors (TFTs) employing spray-coated ZnO
      as the active semiconducting channels. The films are studied by UV-visible
      absorption spectroscopy, spectroscopic ellipsometry, impedance spectroscopy,
      atomic force microscopy, X-ray diffraction and field-effect measurements.
      Analyses reveal amorphous Al2x-1.TixOy dielectrics that exhibit a wide band gap
      (~4.5 eV), low roughness (~0.9 nm), high dielectric constant (k ~ 13), Schottky
      pinning factor S of ~0.44 and very low leakage currents (<5 nA/cm(2)). TFTs
      employing stoichiometric Al2O3.TiO2 gate dielectrics and ZnO semiconducting
      channels exhibit excellent electron transport characteristics with low operating
      voltages (~10 V), negligible hysteresis, high on/off current modulation ratio of
      ~10(6), subthreshold swing (SS) of ~550 mV/dec and electron mobility of ~10 cm(2)
      V(-1) s(-1). 

PMID- 25774575
TI  - Filtration-based synthesis of micelle-derived composite membranes for high-flux
      ultrafiltration.
AB  - Ideal membrane configurations for efficient separation at high flux rates consist
      of thin size-selective layers connected to macroporous supports for mechanical
      stabilization. We show that micelle-derived (MD) composite membranes combine
      efficient separation of similarly sized proteins and water flux 5-10 times higher
      than that of commercial membranes with similar retentions. MD composite membranes
      were obtained by filtration of solutions of amphiphilic block copolymer (BCP)
      micelles through commercially available macroporous supports covered by
      sacrificial nanostrand fabrics followed by annealing and removal of the
      nanostrand fabrics. Swelling-induced pore generation in the BCP films thus
      covering the macroporous supports yielded ~210 nm thin nanoporous size-selective
      BCP layers with porosities in the 40% range tightly connected to the macroporous
      supports. Permselectivity and flux rates of the size-selective BCP layers were
      adjusted by the BCP mass deposited per membrane area and by proper selection of
      swelling times. The preparation methodology described here may pave the way for a
      modular assembly system allowing the design of tailored separation membranes. 

PMID- 25774576
TI  - Functional label-free assays for characterizing the in vitro mechanism of action
      of small molecule modulators of capsid assembly.
AB  - HIV capsid protein is an important target for antiviral drug design. High
      throughput screening campaigns have identified two classes of compounds (PF74 and
      BI64) that directly target HIV capsid, resulting in antiviral activity against
      HIV-1 and HIV-2 laboratory strains. Using recombinant proteins, we developed a
      suite of label-free assays to mechanistically understand how these compounds
      modulate capsid activity. PF74 preferentially binds to the preassembled hexameric
      capsid form and prevents disruption of higher-order capsid structures by
      stabilizing capsid intersubunit interactions. BI64 binds only the monomeric
      capsid and locks the protein in the assembly incompetent monomeric form by
      disrupting capsid intersubunit interactions. We also used these assays to
      characterize the interaction between capsid and the host protein cleavage and
      polyadenylation specific factor 6 (CPSF6). Consistent with recently published
      results, our assays revealed CPSF6 activates capsid polymerization and
      preferentially binds to the preassembled hexameric capsid form similar to the
      small molecule compound, PF74. Furthermore, these label-free assays provide a
      robust method for facilitating the identification of a different class of small
      molecule modulators of capsid function. 

PMID- 25774577
TI  - Ready for Retirement: The Gateway Drug Hypothesis.
AB  - The psycho-social observation that the use of some psychoactive substances
      ("drugs") is often followed by the use of other and more problematic drugs has
      given rise to a cluster of so-called "gateway drug hypotheses," and such
      hypotheses have often played an important role in developing drug use policy. The
      current essay suggests that drug use policies that have drawn on versions of the
      hypothesis have involved an unjustified oversimplification of the dynamics of
      drug use, reflecting the interests of certain stakeholders rather than wise
      social policy. The hypothesis should be retired. 

PMID- 25774579
TI  - [The communication of uncertainty: the lessons of Ebola and the tsunami].
AB  - An enlightening article, recently published in the New England Journal, mentions
      the natural disasters and the epidemic of Ebola to discuss the importance and the
      difficulty of the communication of uncertainty. History shows how difficult it is
      to make a prognostic (and being understood). The story of the tsunami is similar,
      it explains the fear and the difficulty to communicate forecasted events which by
      nature have a certain level of probability and are not a certainty. In this
      article, we take the opportunity to reflect on the changing of our paradigms."How
      can we trust you, if your opinions are always changing?" says the author,
      underlining how this aspect of science is not intuitive.In a time in which our
      work is changing, early dialysis is replaced by intent to delay, palliation
      intensifies along with the pride of being able to start renal replacement therapy
      at any age, pregnancy is made possible on dialysis, the so-called conservative
      therapy is rediscovered. This work can make us wonder about the fragility of
      dogmas and can make us reflect on the importance of communication, in a balance
      between answering to our patients and admitting that, often, we are the first
      ones not to have all the answers.

PMID- 25774580
TI  - [Radiographic disappearance of lanthanum].
AB  - In 2006, Cerny and Kunzendorf in the New England Journal of Medicine Images in
      clinical medicine, showed the radiographic appearance of lanthanum for the first
      time. After many years we noticed the inverse phenomenon. In a peritoneal
      dialysis patient treated with lanthanum carbonate, we had two radiography of the
      abdomen for monitoring the peritoneal catheter. In the first radiography contrast
      material was seen in colon. In the most recent radiography contrast material
      disappeared. The patient was always taking the same dose of lanthanum carbonate
      (1000 mg bid), although at the time of the first radiography he took the chewable
      tablets, for the last radiography he took the new powder formulation. We found a
      report in literature highlighting this phenomenon meanwhile indicating a greater
      chelating effect for the powder. Our hypothesis is that despite the same
      lanthanum dose, powder provides a greater surface area of binding and a more
      dispersed bowel distribution to explain a masked radio-opacity. Considering the
      wide availability of the powder, this must be taken into account especially in
      evaluating therapeutic compliance.

PMID- 25774581
TI  - [Calcific uremic arteriolopathy (Calcyphilaxis): a rare disease? Report of three
      cases].
AB  - INTRODUCTION: Calcific uremic arteriolopathy (CUA; CALCYPHILAXIS) is a syndrome
      that occurs prevalently in patients with chronic kidney disease on dialysis. It
      is characterized by the medial calcification of skin small arteries leading to
      necrotic lesions. Several risk factors have been identified: obesity, female
      gender, diabetes mellitus, hyperphosphatemia, inflammation, treatment with
      vitamin D, calcium-based phosphate binders and warfarin. MATERIALS AND METHODS:
      We report three cases of CUA observed from October 2011 to September 2014.
      RESULTS: The mean age at diagnosis was 56 years (range 33-68). Biochemistry
      showed: mean levels of PTH=1277 pg/ml (range 1000-1696), serum calcium =10.2
      mg/dl (range 9.4-11.1), phosphorus=4.5 mg/dl (range 3.4-5.5). All patients were
      taking vitamin D, two patients were on warfarin therapy. Following actions were
      undertaken: interruption of calcium-based phosphate binders, vitamin D and
      warfarin therapy, initiation of cinacalcet and sodium thiosulfate therapy, use of
      dialysate with lowest available calcium concentration (1.25 mmol/l), Hyperbaric
      Oxygen Therapy, surgical dressings of skin lesions three times a week.
      Significant improvement was observed in mean levels of PTH (331 pg/ml, range 200
      465), serum calcium (8.3 mg/dl, range 7.4-9.6) and phosphorus (3.4 mg/dl, range
      2.6-3.8). In two out of three patients complete healing of ulcerative lesions was
      obtained. CONCLUSIONS: These cases underline the importance of early diagnosis of
      CUA especially in patients with concomitant risk factors and careful clinical
      monitoring, being CUA characterized by a rapid evolution and high mortality.

PMID- 25774582
TI  - [DFPP in myasthenia gravis: case report].
AB  - INTRODUCTION: Myasthenia Gravis (MG) is a neuromuscular disease due to a decrease
      in the number of acetylcholine receptors (AChR) present at the level of the
      neuromuscular junction. It is characterized by weakness and muscle fatigue. The
      pathogenesis of MG would seem to be autoimmune (autoantibodies against AChR,
      Musk, Titin). The treatment of MG includes acetylcholinesterase inhibitors,
      immunosuppressants, intravenous human immunoglobulin, thymectomy and therapeutic
      apheresis. ? MATERIALS AND METHODS: We report a case of a 40-year-old woman,
      suffering from MG, subjected to thymectomy, in therapy with corticosteroids,
      azathioprine and antagonist of acetylcholinesterase. The patient came under our
      observation for the appearance of a severe acute worsening of neurological
      disease unresponsive to medical therapy. She underwent a series of four
      treatments, every other day, of double filtration plasmapheresis (DFPP). ?
      RESULTS AND DISCUSSION?: The DFPP removed from the patient's blood high-molecular
      weight substances. It showed a reduction of Immunoglobulins, Fibrinogen, C3 and
      C4 complement fractions and anti ACh-R Ab.?The DFPP resulted in disappearance of
      symptoms with improvement in motor and sensory conduction parameters evaluated by
      electromyography. ? CONCLUSION: The DFPP quickly reduces the anti ACh-R Ab and
      anti Titin Ab, as well as the risk of infections and allergies, compared to
      Plasma Exchange. It improves clinical symptoms, therefore it is proved to be an
      effective therapy for the acute exacerbation of MG.

PMID- 25774583
TI  - [Central venous blood gas analysis].
AB  - The hemodialysis might interfere with patients hemodynamic, as the technique
      allows a sophisticated game with extra and intravascular fluids. As the
      cardiocirculatory response could sometimes be unpredictable, it is interesting to
      collect valuable information by reaching a deep understanding of the tissue
      metabolism which is mirrored by the blood gas analysis of variations in arterial
      and central venous blood samples. Particularly interesting are the time course
      variations of the central venous hemoglobin saturation (ScvO2), which are
      directly related to the patient with O2-demand as well as to the O2-Delivery
      (DO2). The ScvO2 is determined by four parameters (cardiac output, Hb
      concentration, arterial Hb saturation and O2 consumption): If the fluids
      subtraction during dialysis was about to determine an occult hypoperfusion, the
      ScvO2 reduction would be a timely warning sign to be considered. Moreover, while
      the normal veno-arterial PCO2 difference is 2-4 mmHg, whenever a mismatch between
      O2-demand and DO2arise, a larger v-aPCO2 difference should be observed.

PMID- 25774584
TI  - [Hyponatremia in clinical practice].
AB  - Hyponatremia is the most frequent electrolyte disorder in hospitalized patients
      and it is associated with unfavorable clinical outcomes as well as increased
      hospital costs. Its clinical presentation may be highly variable, ranging from
      asymptomaticity to neurologic emergencies with seizures or coma as signs of
      rapidly worsening cerebral edema. In these cases, prompt treatment is mandatory
      to avoid the patients death. On the other hand, in the case of gradual
      development of hyponatremia, it is imperative that its correction be also
      appropriately slow in order to avoid another neurological catastrophe, namely the
      osmotic demyelination syndrome. Whilst recent international guidelines and expert
      consensus agree on the approach to the treatment of acute severe and symptomatic
      hyponatremia, the recommendations on pharmacological therapy in chronic
      hyponatremia diverge, particularly as to the potential use of vasopressin
      antagonists. This review is aimed at summarizing essential aspects of
      epidemiology, pathophysiology and the diagnostic process of hyponatremia, to set
      the ground for a practical as well as evidence-based approach to treatment. As a
      guide through the discussion of the available evidence, a clinical case is
      presented in which the patients history and laboratory data are crucial for
      identifying the etiology of hyponatremia. The severe neurological signs at
      presentation justify an emergency treatment with hypertonic saline, as indicated.
      Subsequently, as the neurological emergency subsides, we discuss the need to
      revert the trend towards hypercorrection by an apparently counterintuitive
      approach, based in fact on sound pathophysiological grounds, with continuous
      infusion of hypotonic solutions and administration of desmopressin. 

PMID- 25774585
TI  - [Multi-organ failure after massive Levothyroxine ingestion: case report].
AB  - Levothyroxine is the drug of choice prescribed worldwide for the treatment of
      Hypothyroidism. The exact daily dosage, mode of consumption and refractoriness to
      therapy are still subject of discussion. The intoxication with levothyroxine is
      rare and with severe complications in adults; on the contrary, high prevalence
      and benign course is observed in pediatric age. We report the case of a 56 year
      old woman, presented to the emergency department after intentional ingestion of
      massive levothyroxine overdose , with acute renal failure, severe disturbances of
      cardiovascular and central nervous system, that required intensive care support.
      In absence of a specific treatment, plasmapheresis has been used with good
      results, despite important clinical complications. In fact the clinical
      applications of plasmapheresis are rapidly increasing in number and scope: the
      plasmapheresis appears to be a very important tool for the treatment of acute and
      severe forms of thyrotoxicosis due to l-thyroxine intoxication. 

PMID- 25774586
TI  - [Is it feasible to improve the duration and the efficiency of Ramipril anti
      proteinuric response?].
AB  - BACKGROUND: Ramipril administered once daily is characterized by an attenuation
      of its pharmacological activity in the following 24 hours, whose effects on
      antiproteinuric activity have not yet been investigated. METHODS: The
      antiproteinuric efficacy of Ramipril has been evaluated in a cross-over study in
      20 patients with renal disease, proteinuria and hypertension (GFR50 mL / min,
      proteinuria <3 g / day; SBP/DBP 150/90 mmHg). Proteinuria was measured over 24
      hours on three consecutive urine collections (morning, afternoon and night) in
      the absence of antiproteinuric drugs and after ten days of treatment with single
      morning administration of Ramipril 2.5 mg or Ramipril 10 mg. RESULTS: At
      baseline: mean proteinuria was not significantlychanged over the course of the
      three urinary collections (88 7.2 mg/h in the morning of 80 10.5 mg/h in the
      afternoon and 81 10.1 mg/hr during the night). After Ramipril 2.5 mg/day: slight
      reduction in mean proteinuria, with no significant differences between
      collections (80 11 mg/h in the morning, 69 7.4 mg/h in the afternoon and 75 9.1
      mg/h during the night). After Ramipril 10 mg/day: afternoon and night values of
      proteinuria were significantly reduced compared to baseline; noctural proteinuria
      was significantly lower than morning value (51 7.5 mg/h vs. 81 10 mg/h, p <0.05).
      CONCLUSION: The antiproteinuric effectiveness of Ramipril tends to decrease
      significantly over the 24hours after a single daily administration. An increase
      and/or division of Ramipril dose might help to stabilize and to maximizeits
      antiproteinuric effectiveness.

PMID- 25774587
TI  - [The use of therapeutic apheresis in neurological diseases and comparison between
      plasma exchange and immunoadsorption].
AB  - The use of plasmapheresis in neurological diseases with immune-mediated
      pathogenesis is widely certified. In recent years, the technological evolution of
      the dialysis membranes allowed to accompany the classical plasma exchange (PEX)
      treatment of apheresis by means of selective adsorption (IA). It has proved to be
      of equal therapeutic efficacy and, at the same time, devoid of most of the PEX
      side effects. The recent guidelines of the American Society for Apheresis (ASFA)
      and, later, the American Academy of Neurology, outlined directions and diagrams
      for the application of the method that has found wide use in many neurological
      diseases on the basis of auto-antibodies; in particular in Myasthenia Gravis,
      Guillain-Barre Syndrome, Multiple Sclerosis and Chronic Demyelinating
      Polyradiculoneuropathy. We add our experience in the treatment of 13 patients
      suffering from Myasthenia Gravis, treated over a four years period with filters
      containing tryptophan immunoadsorption in polyvinyl alcohol gel. The results
      confirm the achievement of a rapid regression of clinical symptoms, together with
      the rapid fall in the levels of antibody against acetylcholine-receptor.
      Therefore, the method of AI is to be considered of equal therapeutic efficacy of
      PEX, providing greater security in its use. 

PMID- 25774588
TI  - [Disglycemia in patients with acute kidney injury in the ICU].
AB  - Derangements of glucose metabolism are common among critically ill patients.
      Critical illness- associated hyperglycemia (CIAH) is characterized by raised
      blood glucose levels in association with an acute event that is reversible after
      resolution of the underlying disease. CIAH has many causes, such as changes in
      counter-regulatory hormone status, release of sepsis mediators, insulin
      resistance, drugs and nutritional factors. It is associated with increased
      mortality risk. This association appears to be strongly influenced by diabetes
      mellitus as a comorbidity, suggesting the need for an accurate individualization
      of glycemic targets according to baseline glycemic status. Hypoglycemia is also
      very common in this clinical context and it has a negative prognostic impact.
      Many studies based on intensive insulin treatment protocols targeting normal
      blood glucose values have in fact documented both an increased incidence of
      hypoglycemia and an increased mortality risk. Finally, glycemic control in the
      ICU is made even more complex in the presence of acute kidney injury. On one
      hand, there is in fact a reduction of both the renal clearance of insulin and of
      gluconeogenesis by the kidney. On the other hand, the frequent need for renal
      replacement therapy (dialysis / hemofiltration) may result in an energy intake
      excess, under the form of citrate, lactate and glucose in the
      dialysate/reinfusion fluids. With regard to the possible renal protective effects
      afforded by intensive glycemic control protocols, the presently available
      evidence does not support a reduction in the incidence of AKI and/or the need for
      RRT with this approach, when compared with standard glucose control. Thus, the
      most recent guidelines now suggest higher blood glucose targets (<180 mg/dl or
      140-180 mg/dl) than in the past (80-110 mg/dl). Albeit with limited evidence, it
      seems reasonable to extend these indications also to patients with AKI in the
      intensive care unit. Further studies are needed in order to better ascertain the
      effects of dysglycemia on the outcome of patients with AKI. 

PMID- 25774589
TI  - [Renal biopsy in the lateral position in high risk patients: an opportunity to
      take advantage of].
AB  - Percutaneous ultrasound-guided renal biopsy (RB) is the gold standard for
      diagnosis of renal diseases. The standard procedure involves biopsy in the prone
      position (PP) for the native kidneys. In high risk patients, transjugular and
      laparoscopic RB have been proposed. In patients suffering from obesity or
      respiratory diseases, the RB of the native kidney in the supine anterolateral
      position (SALP) represents an alternative to these invasive and expensive
      methods. We illustrate the technique of execution of RB in the lateral position
      (LP) on native kidneys. The procedure is safe, effective and has reduced the path
      travelled by the needle biopsy compared with PP and SALP. 

PMID- 25774590
TI  - [Pregnancy, CKD and solitary kidney: kidney donation between clinical logic and
      taboos].
AB  - On the occasion of the Congress of the American Society of Nephrology, the yearly
      issue of the NEJM introduces a selection of articles of interest for Nephrology,
      drawing attention to the incidence of hypertensive disorders of pregnancy in
      kidney donors. The article reconsiders this issue five years after two studies
      that described an increase in risk for adverse pregnancy outcomes after kidney
      donation. It disproves a previous assumption of "non-interference" between kidney
      donation and pregnancy outcomes. Meanwhile,CKD has been recognized as a risk
      factor for pregnancy, regardless of the presence of reduced renal function,
      hypertension and proteinuria, although these factors modulate the risk. In the
      discussion, the authors help to dispel the taboos that donor women are
      substantially different from women born with a solitary kidney or were so as an
      effect of a disease. Beside the issue of transplantation,the study indicates that
      we have to pay attention to all patients with CKD in pregnancy, giving us a very
      interesting clue for counselling. The risk of complications is greater in the
      donor population compared to a "low risk" population, but it is roughly equal to
      that of the general population, if the latter is not subject to a careful
      clinical work-up. Control and follow-up offset the risk: in a time when economic
      cuts to health care are almost killing the prevention programs, this is probably
      the most important message. 

PMID- 25774591
TI  - [Probing the dry weight in hemodialysis: is bioimpedance the solution?].
AB  - Probing the dry weight (DW) was largely dependent on clinical subjective estimate
      until recently. New bedside non-invasive tools have been developed with the aim
      of providing more objective information on volume status and guiding physicians
      in the quest for DW. Among them, bioimpedance (BIA) appears to be very promising
      in the achievement of this goal. Resistance (R) and capacitance of tissue are the
      two basic properties in BIA. However, although impedance is an electrical
      property of tissues that can be directly used in body composition analysis, it is
      commonly embedded in predictive equations that are derived by correlation with
      criterion measures of body compartments. In recent studies continuous regional
      calf multifrequency BIA spectroscopy and wrist-to-ankle whole-body single
      frequency BIA were used during dialysis sessions to assess DW. The latter was
      defined as the weight achieved after flattening of the R0/Rt slope (R0 is R at
      time 0 and Rt is R at at a given time t during the HD session) for a period of at
      least 20 minutes despite ongoing ultrafiltration, indicating no further decline
      in extracellular volume. Two are the main advantages of these methods: they use
      directly R, with no need for predictive equations; they do not depend on
      comparison with healthy subjects but mainly use patients as their own control to
      define DW as stabilization of the R0/Rt slope. In conclusion, clinical methods
      are fundamental in probing the DW. They must be supported by strict BIA
      protocols. BIA appears to be a (the) brilliant solution in solving the old
      problem of DW in hemodialysis patients.

PMID- 25774592
TI  - [Efficacy and effectiveness].

PMID- 25774593
TI  - [Identikit of the patient who chooses the PD. Experience of the Autonomous
      Province of Trento].
AB  - Peritoneal dialysis is a method still underused in Italy. In the Autonomous
      Province of Trento (PAT) since 2008 has been implemented, with excellent results,
      a program for the enhancement of the use of this therapy. The most important
      innovation was the introduction of a questionnaire proposed by nurses to patients
      in pre-dialysis colloquia. The questionnaire aimed to outline the patient
      personal and family profile in relation to the chosen dialysis methods. We
      analyzed 174 questionnaires collected from 1/04/2008 to 01/12/2015. Among these
      84 patients had opted for the peritoneal dialysis (PD) and 90 had chosen the
      Hemodialysis (HD). The questionnaire comparison shown that the patient who opted
      for the PD have a more positive attitude towards this method. PD patient had more
      often a job, lived far away from the center of HD, had more frequently the
      support of a family and had a psychological profile more "sad" or "emotional"
      than the HD patient, who was more "insecure". On the other hand, factors like
      age, type of family, degree of autonomy and nationality do not affect the choice
      about dialysis. 

PMID- 25774594
TI  - 5-Azacytidine and DLI can induce long-term remissions in AML patients relapsed
      after allograft.
AB  - DNA-hypomethylating agents are a viable treatment option for AML/myelodysplastic
      syndrome (MDS) relapse after allograft by upregulating Ags on blasts before DLI.
      Seventy-two patients with relapsed AML (n=62), MDS (n=8) and other myeloid
      neoplasms (n=2) after allograft were treated with low-dose 5-azacytidine and, if
      feasible, DLI. PATIENT CHARACTERISTICS: median age 62 years (range 20-75), 42%
      with adverse cytogenetics, 82% not in remission at transplant and 83% received
      fludarabine-based reduced-toxicity conditioning. Median duration from transplant
      to 5-azacytidine was 289 days (range 59-2133). Response criteria: CR, temporary
      disease control or treatment failure. A median of 2.7 courses (range 1-10) were
      administered; 65 out of 72 patients also received DLI (41 already before 5
      azacytidine). Ten patients developed acute GVHD and two succumbed to treatment
      related sepsis. CR rate was 9.7% (in two patients lasting >5 years), 44% had
      temporary disease control (median duration 71 days, range 31-380). Median
      survival from 5-azacytidine was 108 days, 21 patients proceeded to subsequent
      transplant. In multivariate analysis, peripheral blood blasts <1% were predictive
      of longer OS (P=0.03). Taken together, long-term remissions can be induced by
      this well-tolerated outpatient treatment, particularly in patients without
      peripheral blood blasts.

PMID- 25774595
TI  - Risk model incorporating donor IL6 and IFNG genotype and gastrointestinal GVHD
      can discriminate patients at high risk of steroid refractory acute GVHD.
AB  - Steroid refractory acute GVHD (SR aGVHD) is associated with high morbidity and
      mortality. This study attempted to generate a risk model for SR aGVHD using 259
      single nucleotide polymorphisms (SNPs) in 53 genes of recipients and donors. A
      total of 268 patients with aGVHD who were treated with systemic steroids were
      included. Patients were randomly divided into training (n=180) and validation
      sets (n=88). Clinical risk factors were also evaluated. In the training set, 85
      (47.2%) developed SR aGVHD. Gastrointestinal involvement (P<0.0001) and donor
      genotypes of IL6 (rs1800797; P=6.2 * 10(-4)) and IFNG (rs2069727; P=4.4 * 10(-4))
      were significant risk factors. Scores were assigned to the above risk factors.
      Patients were divided into low (score 0, n=74) vs high risk (scores 1-3; n=106)
      in risk model. Higher incidence of SR aGVHD was noted in the high risk (61.3%) vs
      the low-risk group (27%; P<0.0001, odds ratio (OR) 4.28). Predictive effect of
      risk model was replicated in the validation set (P=0.0045, OR 3.74). This risk
      model was associated with response to therapy, overall and GVHD-specific survival
      and non-relapse mortality. Our study suggested that this risk model could
      identify patients at high risk of SR aGVHD with donor genotype of IL6 (rs1800797)
      and IFNG (rs2069727) along with gastrointestinal involvement of aGVHD. 

PMID- 25774596
TI  - Traffic Light: prognosis-based eligibility for clinical trials of hematopoietic
      SCT in adults with sickle cell anemia.
AB  - Estimating prognosis in sickle cell anemia (SCA) assumes greater importance as
      intensive treatments, such as hematopoietic SCT (HSCT), are being tested. Here we
      estimate the mortality risk from the walk-PHaSST (Sildenafil Therapy for
      Pulmonary Hypertension and Sickle Cell Disease) trial of homozygous SCA patients
      with suspected pulmonary hypertension (19/468 deaths; 10 centers in the US and
      UK). Parallel investigations were also undertaken in the Cooperative Study of
      Sickle Cell Disease (CSCCD) and a contemporary urban sickle cell disease
      population (Case Western Reserve University-University Hospitals (CWRU-UH),
      Cleveland, OH, USA). One- and two-value positive predictive values for 2-year
      mortality (from study entry) are calculated using factors that include
      demographics, laboratory values and clinical evaluations. We define high-,
      intermediate-, and low-risk SCA as > 15%, 10-15% and < 10% 2-year mortality. In
      walk-PHaSST, no single factor qualifies as high-risk SCA, although several
      combinations of two factors (that is, both age > 35 years and history of chronic
      transfusion) do. Either elevated white blood cell count (> 13.5 * 10(3)
      cells/mcL, 7/70 deaths) or elevated Tricuspid Regurgitant Jet Velocity (? 3.0
      m/s, 8/67 deaths) was individually associated with intermediate-risk disease, as
      were many two-factor combinations. N-terminal pro-brain natriuretic peptide > 160
      ng/L, lactate dehydrogenase > 600 IU/L, history of chronic transfusion, sepsis or
      age > 35 years are individually associated with low-risk SCA, as are many two
      factor combinations. SCA risk was integrated with estimated donor type-associated
      risk from HSCT to form 'Traffic Light' eligibility criteria for clinical trials
      of HSCT. This method is adaptable to evolutions in clinical care.

PMID- 25774597
TI  - The Phenomenological, Social Network, Social Norms, and Economic Context of
      Substance Use and HIV Prevention and Treatment: A Poverty of Meanings.

PMID- 25774598
TI  - A methodological framework for drug development in rare diseases.
AB  - INTRODUCTION: Developing orphan drugs is challenging because of their severity
      and the requisite for effective drugs. The small number of patients does not
      allow conducting adequately powered randomized controlled trials (RCTs). There is
      a need to develop high quality, ethically investigated, and appropriately
      authorized medicines, without subjecting patients to unnecessary trials. AIMS AND
      OBJECTIVES: The main aim is to develop generalizable framework for choosing the
      best-performing drug/endpoint/design combinations in orphan drug development
      using an in silico modeling and trial simulation approach. The two main
      objectives were (i) to provide a global strategy for each disease to identify the
      most relevant drugs to be evaluated in specific patients during phase III RCTs,
      (ii) and select the best design for each drug to be used in future RCTs.
      METHODOLOGICAL APPROACH: In silico phase III RCT simulation will be used to find
      the optimal trial design and was carried out in two steps: (i) statistical
      analysis of available clinical databases and (ii) integrative modeling that
      combines mathematical models for diseases with pharmacokinetic-pharmacodynamics
      models for the selected drug candidates. CONCLUSION: There is a need to speed up
      the process of orphan drug development, develop new methods for translational
      research and personalized medicine, and contribute to European Medicines Agency
      guidelines. The approach presented here offers many perspectives in clinical
      trial conception.

PMID- 25774599
TI  - Actin dynamics tune the integrated stress response by regulating eukaryotic
      initiation factor 2alpha dephosphorylation.
AB  - Four stress-sensing kinases phosphorylate the alpha subunit of eukaryotic
      translation initiation factor 2 (eIF2alpha) to activate the integrated stress
      response (ISR). In animals, the ISR is antagonised by selective eIF2alpha
      phosphatases comprising a catalytic protein phosphatase 1 (PP1) subunit in
      complex with a PPP1R15-type regulatory subunit. An unbiased search for additional
      conserved components of the PPP1R15-PP1 phosphatase identified monomeric G-actin.
      Like PP1, G-actin associated with the functional core of PPP1R15 family members
      and G-actin depletion, by the marine toxin jasplakinolide, destabilised the
      endogenous PPP1R15A-PP1 complex. The abundance of the ternary PPP1R15-PP1-G-actin
      complex was responsive to global changes in the polymeric status of actin, as was
      its eIF2alpha-directed phosphatase activity, while localised G-actin depletion at
      sites enriched for PPP1R15 enhanced eIF2alpha phosphorylation and the downstream
      ISR. G-actin's role as a stabilizer of the PPP1R15-containing holophosphatase
      provides a mechanism for integrating signals regulating actin dynamics with
      stresses that trigger the ISR. 

PMID- 25774600
TI  - G-actin provides substrate-specificity to eukaryotic initiation factor 2alpha
      holophosphatases.
AB  - Dephosphorylation of eukaryotic translation initiation factor 2a (eIF2a) restores
      protein synthesis at the waning of stress responses and requires a PP1 catalytic
      subunit and a regulatory subunit, PPP1R15A/GADD34 or PPP1R15B/CReP. Surprisingly,
      PPP1R15-PP1 binary complexes reconstituted in vitro lacked substrate selectivity.
      However, selectivity was restored by crude cell lysate or purified G-actin, which
      joined PPP1R15-PP1 to form a stable ternary complex. In crystal structures of the
      non-selective PPP1R15B-PP1G complex, the functional core of PPP1R15 made multiple
      surface contacts with PP1G, but at a distance from the active site, whereas in
      the substrate-selective ternary complex, actin contributes to one face of a
      platform encompassing the active site. Computational docking of the N-terminal
      lobe of eIF2a at this platform placed phosphorylated serine 51 near the active
      site. Mutagenesis of predicted surface-contacting residues enfeebled
      dephosphorylation, suggesting that avidity for the substrate plays an important
      role in imparting specificity on the PPP1R15B-PP1G-actin ternary complex. 

PMID- 25774601
TI  - Social networks predict gut microbiome composition in wild baboons.
AB  - Social relationships have profound effects on health in humans and other
      primates, but the mechanisms that explain this relationship are not well
      understood. Using shotgun metagenomic data from wild baboons, we found that
      social group membership and social network relationships predicted both the
      taxonomic structure of the gut microbiome and the structure of genes encoded by
      gut microbial species. Rates of interaction directly explained variation in the
      gut microbiome, even after controlling for diet, kinship, and shared
      environments. They therefore strongly implicate direct physical contact among
      social partners in the transmission of gut microbial species. We identified 51
      socially structured taxa, which were significantly enriched for anaerobic and non
      spore-forming lifestyles. Our results argue that social interactions are an
      important determinant of gut microbiome composition in natural animal populations
      a relationship with important ramifications for understanding how social
      relationships influence health, as well as the evolution of group living. 

PMID- 25774602
TI  - Rapid epigenetic adaptation to uncontrolled heterochromatin spreading.
AB  - Heterochromatin, a highly compact chromatin state characterized by histone H3K9
      methylation and HP1 protein binding, silences the underlying DNA and influences
      the expression of neighboring genes. However, the mechanisms that regulate
      heterochromatin spreading are not well understood. In this study, we show that
      the conserved Mst2 histone acetyltransferase complex in fission yeast regulates
      histone turnover at heterochromatin regions to control heterochromatin spreading
      and prevents ectopic heterochromatin assembly. The combined loss of Mst2 and the
      JmjC domain protein Epe1 results in uncontrolled heterochromatin spreading and
      massive ectopic heterochromatin, leading to severe growth defects due to the
      inactivation of essential genes. Interestingly, these cells quickly recover by
      accumulating heterochromatin at genes essential for heterochromatin assembly,
      leading to their reduced expression to restrain heterochromatin spreading. Our
      studies discover redundant pathways that control heterochromatin spreading and
      prevent ectopic heterochromatin assembly and reveal a fast epigenetic adaptation
      response to changes in heterochromatin landscape. 

PMID- 25774603
TI  - Effects of inhaled citronella oil and related compounds on rat body weight and
      brown adipose tissue sympathetic nerve.
AB  - Citronella oil is one of the most famous Indonesian essential oils, having a
      distinctive aroma. As with other essential oils, it is crucial to explore the
      effects of inhalation of this oil. Therefore, the aim of this research was to
      elucidate the effects of inhalation of citronella oil and its components isolated
      from Cymbopogon nardus L. (Poaceae), Indonesian local name: "Sereh Wangi" on the
      body weight, blood lipid profile, and liver function of rats, as well as on the
      sympathetic nerve activity and temperature of brown adipose tissue. Sprague
      Dawley male adult rats fed with high fat diet (HFD) were made to inhale
      citronella oil, R-(+)-citronellal, and beta-citronellol for five weeks, and the
      observations were compared to those of HFD rats that were not subjected to
      inhalation treatment. The results showed that inhalation of beta-citronellol
      decreased feed consumption. As a consequence, the percentage of weight gain
      decreased compared with that in control group and the blood cholesterol level in
      the beta-citronellol group was significantly lowered. Concentration of liver
      function enzymes were not significantly different among the groups. In
      conclusion, inhalation of citronella oil, specifically beta-citronellol,
      decreased body weight by decreasing appetite, without any marked changes in liver
      enzyme concentrations. 

PMID- 25774604
TI  - Live longer with vitamin D?
AB  - The global burden of vitamin D deficiency or insufficiency is of great concern
      for public health. According to recent studies, vitamin D deficiency is an
      important etiological factor in the pathogenesis of many chronic diseases.
      Whether or not there is a connection between 25-hydoxyvitamin D (25(OH)D) status
      and overall mortality is a matter of considerable debate. A new meta-analysis
      confirmed that low 25(OH)D levels were associated with a significant increased
      risk for all-cause mortality. Individuals with severe vitamin D deficiency have
      almost twice the mortality rate as those with 25(OH)D level >= 30 ng/mL, (>=75
      nmol/L). Unlike previous meta-analyses which suggested that serum 25(OH)D > 50
      ng/mL was associated with increased mortality, this new analysis found that there
      was no increased risk even when 25(OH)D levels were >=70 ng/mL. In general,
      closer attention should be paid to vitamin D deficiency in medical and
      pharmaceutical practice than has been the case hitherto. The results of these
      studies are consistent with the recommendation to improve the general vitamin D
      status in children and adults by means of a healthy approach to sunlight
      exposure, consumption of foods containing vitamin D and supplementation with
      vitamin D preparations. 

PMID- 25774607
TI  - Estimating excess hazard ratios and net survival when covariate data are missing:
      strategies for multiple imputation.
AB  - BACKGROUND: Net survival is the survival probability we would observe if the
      disease under study were the only cause of death. When estimated from routinely
      collected population-based cancer registry data, this indicator is a key metric
      for cancer control. Unfortunately, such data typically contain a non-negligible
      proportion of missing values on important prognostic factors (eg, tumor stage).
      METHODS: We carried out an empirical study to compare the performance of complete
      records analysis and several multiple imputation strategies when net survival is
      estimated via a flexible parametric proportional hazards model that includes
      stage, a partially observed categorical covariate. Starting from fully observed
      cancer registry data, we induced missingness on stage under three scenarios. For
      each of these scenarios, we simulated 100 incomplete datasets and evaluated the
      performance of the different strategies. RESULTS: Ordinal logistic models are not
      suitable for the imputation of tumor stage. Complete records analysis may lead to
      grossly misleading estimates of net survival, even when the missing data
      mechanism is conditionally independent of survival time given the covariates and
      the bias on the excess hazard ratios estimates is negligible. CONCLUSIONS: As key
      covariates are unlikely missing completely at random, studies estimating net
      survival should not use complete records. When the missingness can be inferred
      from available data, appropriate multiple imputation should be performed. In the
      context of flexible parametric proportional hazards models with a partially
      observed stage covariate, a multinomial logistic imputation model for stage
      should be used and should include the Nelson-Aalen cumulative hazard estimate and
      the event indicator.

PMID- 25774606
TI  - Short-term effects of a high nitrate diet on nitrate metabolism in healthy
      individuals.
AB  - Dietary nitrate, through the enterosalivary nitrate-nitrite-NO pathway, can
      improve blood pressure and arterial stiffness. How long systemic nitrate and
      nitrite remain elevated following cessation of high nitrate intake is unknown. In
      19 healthy men and women, the time for salivary and plasma nitrate and nitrite to
      return to baseline after 7 days increased nitrate intake from green leafy
      vegetables was determined. Salivary and plasma nitrate and nitrite was measured
      at baseline [D0], end of high nitrate diet [D7], day 9 [+2D], day 14 [+7D] and
      day 21 [+14D]. Urinary nitrite and nitrate was assessed at D7 and +14D. Increased
      dietary nitrate for 7 days resulted in a more than fourfold increase in saliva
      and plasma nitrate and nitrite (p < 0.001) measured at [D7]. At [+2D] plasma
      nitrite and nitrate had returned to baseline while saliva nitrate and nitrite
      were more than 1.5 times higher than at baseline levels. By [+7D] all metabolites
      had returned to baseline levels. The pattern of response was similar between men
      and women. Urinary nitrate and nitrate was sevenfold higher at D7 compared to
      +14D. These results suggest that daily ingestion of nitrate may be required to
      maintain the physiological changes associated with high nitrate intake. 

PMID- 25774605
TI  - Understanding the role of maternal diet on kidney development; an opportunity to
      improve cardiovascular and renal health for future generations.
AB  - The leading causes of mortality and morbidity worldwide are cardiovascular
      disease (high blood pressure, high cholesterol and renal disease), cancer and
      diabetes. It is increasingly obvious that the development of these diseases
      encompasses complex interactions between adult lifestyle and genetic
      predisposition. Maternal malnutrition can influence the fetal and early life
      environment and pose a risk factor for the future development of adult diseases,
      most likely due to impaired organogenesis in the developing offspring. This then
      predisposes these offspring to cardiovascular disease and renal dysfunction in
      adulthood. Studies in experimental animals have further illustrated the
      significant impact maternal diet has on offspring health. Many studies report
      changes in kidney structure (a reduction in the number of nephrons in the kidney)
      in offspring of protein-deprived dams. Although the early studies suggested that
      increased blood pressure was also present in offspring of protein-restricted
      dams, this is not a universal finding and requires clarification. Importantly, to
      date, the literature offers little to no understanding of when in development
      these changes in kidney development occur, nor are the cellular and molecular
      mechanisms that drive these changes well characterised. Moreover, the mechanisms
      linking maternal nutrition and a suboptimal renal phenotype in offspring are yet
      to be discerned-one potential mechanism involves epigenetics. This review will
      focus on recent information on potential mechanisms by which maternal nutrition  
      (focusing on malnutrition due to protein restriction, micronutrient restriction
      and excessive fat intake) influences kidney development and thereby function in
      later life. 

PMID- 25774608
TI  - Telomeres, atherosclerosis, and human longevity: a causal hypothesis.

PMID- 25774611
TI  - Hand dryer noise in public restrooms exceeds 80 dBA at 10 ft (3 m).
AB  - High airflow hand dryers are found in many public restrooms today. These dryers
      offer quick and clean hand drying, and are seen as being an environment-friendly
      alternative to paper towels. However, many new hand dryers are loud, exposing
      individuals using the facilities as well as those employees who clean the
      facilities to potentially dangerous noise. Prolonged exposure to high levels of
      occupational noise can cause damage to hair cells in the cochlea, resulting in
      varying degrees of noise-induced hearing loss. This study examined the intensity
      (in dBA) of the noise produced by the air dryers in campus restrooms. Hand dryer
      peak and average noise was measured with a sound level meter at 2.5 ft, 5 ft, and
      10 ft from the dryer. Noise measurements did not decrease as predicted by the
      inverse-square law, probably because of the reverberative surfaces found in the
      restrooms. The small sample of hand dryers tested was mostly found to be
      producing more noise than the manufacturer claimed they would; indeed, none of
      the dryers would be safe for an 8-h workday exposure. While hand dryers do reduce
      paper trash, they pose as a different sort of hazard to our environment and
      population. 

PMID- 25774610
TI  - Tualang honey improves memory performance and decreases depressive-like behavior
      in rats exposed to loud noise stress.
AB  - Recent evidence has exhibited dietary influence on the manifestation of different
      types of behavior induced by stressor tasks. The present study examined the
      effects of Tualang honey supplement administered with the goal of preventing or
      attenuating the occurrence of stress-related behaviors in male rats subjected to
      noise stress. Forty-eight adult male rats were randomly divided into the
      following four groups: i) nonstressed with vehicle, ii) nonstressed with Tualang
      honey, iii) stressed with vehicle, and iv) stressed with honey. The supplement
      was given once daily via oral gavage at 0.2 g/kg body weight. Two types of
      behavioral tests were performed, namely, the novel object recognition test to
      evaluate working memory and the forced swimming test to evaluate depressive-like
      behavior. Data were analyzed by a two-way analysis of variance (ANOVA) using IBM
      SPSS 18.0. It was observed that the rats subjected to noise stress expressed
      higher levels of depressive-like behavior and lower memory functions compared to
      the unexposed control rats. In addition, our results indicated that the
      supplementation regimen successfully counteracted the effects of noise stress.
      The forced swimming test indicated that climbing and swimming times were
      significantly increased and immobility times significantly decreased in honey
      supplemented rats, thereby demonstrating an antidepressant-like effect.
      Furthermore, cognitive function was shown to be intensely affected by noise
      stress, but the effects were counteracted by the honey supplement. These findings
      suggest that subchronic exposure to noise stress induces depressive-like behavior
      and reduces cognitive functions, and that these effects can be attenuated by
      Tualang honey supplementation. This warrants further studies to examine the role
      of Tulang honey in mediating such effects. 

PMID- 25774612
TI  - Is there an association between aircraft noise exposure and the incidence of
      hypertension? A meta-analysis of 16784 participants.
AB  - To determine if aircraft noise exposure causes an increased incidence of
      hypertension among residents near airports. We conducted a meta-analysis of
      observational studies to evaluate the association between aircraft noise exposure
      and the incidence of hypertension. PubMed, Embase, Web of Science, the Cochrane
      Library, and the Chinese Biomedical Literature Database were searched without any
      restrictions. Odds ratios (ORs) with 95% confidence intervals (CIs) were
      extracted. The pooled ORs were calculated using both the fixed effects model and
      random effects model. All analyses were performed using STATA version 12.0
      software (Stata Corporation, College Station, TX, USA). We examined five studies,
      comprising a total of 16,784 residents. The overall OR for hypertension in
      residents with aircraft noise exposure was 1.63 (95% CI, 1.14-2.33), and one of
      our included studies showed that there was no evidence that aircraft noise is a
      risk factor for hypertension in women. According to our subgroup analysis, the
      summary OR for the incidence was 1.31 (95% CI, 0.85-2.02) with I2 of 80.7% in
      women and 1.36 (95% CI, 1.15-1.60) with moderate heterogeneity in men. The pooled
      OR for the incidence of hypertension in residents aged over 55 years and under 55
      years was 1.66 (95% CI, 1.21-2.27) with no heterogeneity and 1.78 (95% CI, 1.33
      2.39) with I2 of 29.4%, respectively. The present meta-analysis suggests that
      aircraft noise could contribute to the prevalence of hypertension, but the
      evidence for a relationship between aircraft noise exposure and hypertension is
      still inconclusive because of limitations in study populations, exposure
      characterization, and adjustment for important confounders. 

PMID- 25774613
TI  - Fit for the frontline? identification of mission-critical auditory tasks (MCATs)
      carried out by infantry and combat-support personnel.
AB  - The ability to listen to commands in noisy environments and understand acoustic
      signals, while maintaining situational awareness, is an important skill for
      military personnel and can be critical for mission success. Seventeen auditory
      tasks carried out by British infantry and combat-support personnel were
      identified through a series of focus groups conducted by Bevis et al. For
      military personnel, these auditory tasks are termed mission-critical auditory
      tasks (MCATs) if they are carried in out in a military-specific environment and
      have a negative consequence when performed below a specified level. A
      questionnaire study was conducted to find out which of the auditory tasks
      identified by Bevis et al. satisfy the characteristics of an MCAT. Seventy-nine
      British infantry and combat-support personnel from four regiments across the
      South of England participated. For each auditory task participants indicated: 1)
      the consequences of poor performance on the task, 2) who performs the task, and
      3) how frequently the task is carried out. The data were analysed to determine
      which tasks are carried out by which personnel, which have the most negative
      consequences when performed poorly, and which are performed the most frequently.
      This resulted in a list of 9 MCATs (7 speech communication tasks, 1 sound
      localization task, and 1 sound detection task) that should be prioritised for
      representation in a measure of auditory fitness for duty (AFFD) for these
      personnel. Incorporating MCATs in AFFD measures will help to ensure that
      personnel have the necessary auditory skills for safe and effective deployment on
      operational duties. 

PMID- 25774609
TI  - ICBEN review of research on the biological effects of noise 2011-2014.
AB  - The mandate of the International Commission on Biological Effects of Noise
      (ICBEN) is to promote a high level of scientific research concerning all aspects
      of noise-induced effects on human beings and animals. In this review, ICBEN team
      chairs and co-chairs summarize relevant findings, publications, developments, and
      policies related to the biological effects of noise, with a focus on the period
      2011-2014 and for the following topics: Noise-induced hearing loss; nonauditory
      effects of noise; effects of noise on performance and behavior; effects of noise
      on sleep; community response to noise; and interactions with other agents and
      contextual factors. Occupational settings and transport have been identified as
      the most prominent sources of noise that affect health. These reviews demonstrate
      that noise is a prevalent and often underestimated threat for both auditory and
      nonauditory health and that strategies for the prevention of noise and its
      associated negative health consequences are needed to promote public health. 

PMID- 25774614
TI  - Response of cardiac autonomic modulation after a single exposure to musical
      auditory stimulation.
AB  - The acute effects after exposure to different styles of music on cardiac
      autonomic modulation assessed through heart rate variability (HRV) analysis have
      not yet been well elucidated. We aimed to investigate the recovery response of
      cardiac autonomic modulation in women after exposure to musical auditory
      stimulation of different styles. The study was conducted on 30 healthy women aged
      between 18 years and 30 years. We did not include subjects having previous
      experience with musical instruments and those who had an affinity for music
      styles. The volunteers remained at rest for 10 min and were exposed to classical
      baroque (64-84 dB) and heavy metal (75-84 dB) music for 10 min, and their HRV was
      evaluated for 30 min after music cessation. We analyzed the following HRV
      indices: Standard deviation of normal-to-normal (SDNN) intervals, root mean
      square of successive differences (RMSSD), percentage of normal-to-normal 50
      (pNN50), low frequency (LF), high frequency (HF), and LF/HF ratio. SDNN, LF in
      absolute units (ms 2 ) and normalized (nu), and LF/HF ratio increased while HF
      index (nu) decreased after exposure to classical baroque music. Regarding the
      heavy metal music style, it was observed that there were increases in SDNN,
      RMSSD, pNN50, and LF (ms 2 ) after the musical stimulation. In conclusion, the
      recovery response of cardiac autonomic modulation after exposure to auditory
      stimulation with music featured an increased global activity of both systems for
      the two musical styles, with a cardiac sympathetic modulation for classical
      baroque music and a cardiac vagal tone for the heavy metal style. 

PMID- 25774616
TI  - Long-term noise exposure and the risk for type 2 diabetes: a meta-analysis:
      Erratum.

PMID- 25774615
TI  - Occupational noise and myocardial infarction: considerations on the interrelation
      of noise with job demands.
AB  - The present analysis aims to differentiate the association of noise on myocardial
      infarction (MI) by job specific demands using International Standard
      Classification of Occupations (ISCO)-88 codes as a proxy. Data of a German case
      control study were supplemented by job descriptions (indicated by ISCO-88). It
      was examined whether the demands in the various occupational groups modify the
      effect of noise. Noise and occupational groups are combined to form new exposure
      categories. Conditional logistic regression models were fitted to identify
      effects of combined job-noise categories. For the highest noise range (95-124
      dB(A)) we found a significant odds-ratio (OR) of 2.18 (confidence interval [CI]
      0.95 = 1.17-4.05) independent of the profession. Some interesting results were
      found indicating ISCO groups with possible risk. In men, noticeable effects for
      the exposure category between 62 dB(A) and 84 dB(A) are calculated in the group
      of legislators and senior officials (ISCO-group 11; OR=1.93; CI (0.95) = 0.50
      7.42), the group consisting of life science and health professionals (ISCO-group
      22; OR=2.18; CI 0.95 = 0.36-13.1), the group of life science and health associate
      professionals (ISCO-group 32; OR = 2.03; CI 0.95 = 0.50-8.24), and the group of
      "precision, handicraft, printing, and related trades workers" (ISCO-group 73; OR
      = 2.67; CI(0.95) = 0.54-13.0). In the exposure range of 85-94 dB(A), high ORs are
      calculated for "skilled agricultural, fishery, and forestry workers" (ISCO-group
      6; OR = 4.31; CI(0.95) = 0.56-33.3). In women, there are high (nonsignificant)
      ORs in ISCO-group 1 (OR = 2.43; CI(0.95) = 0.12-50.0), ISCO-group 2 (OR = 1.80;
      CI 0.95 = 0.31-10.5), and ISCO-group 9 (OR = 2.45; CI(0.95) = 0.63-9.51) for a
      noise exposure between 62 dB(A) and 84 dB(A). When investigating noise at the
      workplace in relation to cardiovascular diseases it is important to take the
      specific requirements of a job into account. Thus, work tasks with high health
      risks can be identified that helps to develop appropriate prevention strategies.

PMID- 25774618
TI  - Substandard vaccination compliance and the 2015 measles outbreak.

PMID- 25774617
TI  - Immune approaches to the treatment of breast cancer, around the corner?
AB  - Immunotherapy for the treatment of breast cancer can be categorized as either (a)
      specific stimulation of the immune system by active immunization, with cancer
      vaccines, or (b) passive immunization, such as tumor-specific antibodies
      (including immune modulators) or adoptive cell therapy that inhibit the function
      of, or directly kill, tumor cells. We will present the current information and
      the future perspectives of immunotherapy in patients with breast cancer,
      including the prognostic role of tumor infiltrating lymphocytes, immune
      signatures, targeted therapies modulating the immune system, and tumor antigen
      cancer vaccines. Active immunotherapy in breast cancer and its implementation
      into clinical trials have been largely a frustrating experience in the last
      decades. The concept that the immune system regulates cancer development is
      experiencing a new era of interest. It is clear that the cancer
      immunosurveillance process indeed exists and potentially acts as an extrinsic
      tumor suppressor. Also, the immune system can facilitate tumor progression by
      sculpting the immunogenic phenotype of tumors as they develop. Cancer
      immunoediting represents a refinement of the cancer immunosurveillance hypothesis
      and resumes the complex interaction between tumor and immune system into three
      phases: elimination, equilibrium, and escape. Major topics in the field of
      immunology deserve a response: what do we know about tumor immunogenicity, and
      how might we therapeutically improve tumor immunogenicity? How can we modulate
      response of the immune system? Is there any gene signature predictive of response
      to immune modulators? The success of future immunotherapy strategies will depend
      on the identification of additional immunogenic antigens that can serve as the
      best tumor-rejection targets. Therapeutic success will depend on developing the
      best antigen delivery systems and on the elucidation of the entire network of
      immune signaling pathways that regulate immune responses in the tumor
      microenvironment. 

PMID- 25774619
TI  - Tailoring surface phase transition and magnetic behaviors in BiFeO3 via doping
      engineering.
AB  - The charge-spin interactions in multiferroic materials (e.g., BiFeO3) have
      attracted enormous attention due to their high potential for next generation
      information electronics. However, the weak and deficient manipulation of charge
      spin coupling notoriously limits their commercial applications. To tailor the
      spontaneous charge and the spin orientation synergistically in BiFeO3 (BFO), in
      this report, the 3d element of Mn doping engineering is employed and unveils the
      variation of surface phase transition and magnetic behaviors by introducing
      chemical strain. The spontaneous ferroelectric response and the corresponding
      domain structures, magnetic behaviors and spin dynamics in Mn-doped BFO ceramics
      have been investigated systematically. Both the surface phase transition and
      magnetization were enhanced in BFO via Mn doping. The interaction between the
      spontaneous polarization charge and magnetic spin reorientation in Mn-doped BFO
      are discussed in detail. Moreover, our extensive electron paramagnetic resonance
      (EPR) results demonstrate that the 3d dopant plays a paramount role in the
      surface phase transition, which provides an alternative route to tune the charge
      spin interactions in multiferroic materials. 

PMID- 25774620
TI  - Is vertebral body osteophytosis a reliable indicator of occupational stress?
AB  - Whether activity patterns cause vertebral body osteophytosis (VO) remains
      unanswered. Although, many previous researchers indicate physical activity as an
      etiological factor of VO, a number of recent studies have questioned this
      conclusion. Thus, using a sample of 101 adult males from medieval Poland, this
      current study examines whether individuals with VO have greater entheseal change
      (EC) scores since EC are commonly used as an indicator of activity. The sample
      was divided into younger adults (20 to 40 years old) and older adults (41 to 56
      years old). Three aggregate variables (aggregate VO, upper limb ECs, and lower
      limb ECs) were created to determine whether VO may be useful in activity pattern
      reconstructions. No significant age differences were found and, thus, all
      correlations were run without age controls. A significant positive correlation
      was found between aggregate VO and lower limb EC (rho = 0.347, p < 0.01). The
      existence of the correlation between aggregate VO and lower limb EC in this study
      implies that vertebral osteophytosis may relate to occupational stresses and
      there may be similar etiologies present in VO and EC formation, but there remains
      much unexplained variance that suggests that VO and EC etiologies are complex. 

PMID- 25774621
TI  - Sub-nanosecond signal propagation in anisotropy-engineered nanomagnetic logic
      chains.
AB  - Energy efficient nanomagnetic logic (NML) computing architectures propagate
      binary information by relying on dipolar field coupling to reorient closely
      spaced nanoscale magnets. Signal propagation in nanomagnet chains has been
      previously characterized by static magnetic imaging experiments; however, the
      mechanisms that determine the final state and their reproducibility over millions
      of cycles in high-speed operation have yet to be experimentally investigated.
      Here we present a study of NML operation in a high-speed regime. We perform
      direct imaging of digital signal propagation in permalloy nanomagnet chains with
      varying degrees of shape-engineered biaxial anisotropy using full-field magnetic
      X-ray transmission microscopy and time-resolved photoemission electron microscopy
      after applying nanosecond magnetic field pulses. An intrinsic switching time of
      100 ps per magnet is observed. These experiments, and accompanying macrospin and
      micromagnetic simulations, reveal the underlying physics of NML architectures
      repetitively operated on nanosecond timescales and identify relevant engineering
      parameters to optimize performance and reliability. 

PMID- 25774622
TI  - Revisiting standard precautions to reduce antimicrobial resistance in nursing
      homes.

PMID- 25774623
TI  - Comparison of the Effects of Seated, Supine, and Walking Interset Rest Strategies
      on Work Rate.
AB  - Ouellette, KA, Brusseau, TA, Davidson, LE, Ford, CN, Hatfield, DL, Shaw, JM, and
      Eisenman, PA. Comparison of the effects of seated, supine, and walking interset
      rest strategies on work rate. J Strength Cond Res 30(12): 3396-3404, 2016-The
      idea that an upright posture should be maintained during the interset rest
      periods of training sessions is pervasive. The primary aim of this study was to
      determine differences in work rate associated with 3 interset rest strategies.
      Male and female members of the CrossFit community (male n = 5, female n = 10)
      were recruited to perform a strenuous training session designed to enhance work
      capacity that involved both cardiovascular and muscular endurance exercises. The
      training session was repeated on 3 separate occasions to evaluate 3 interset rest
      strategies, which included lying supine on the floor, sitting on a flat bench,
      and walking on a treadmill (0.67 m.s). Work rate was calculated for each training
      session by summing session joules of work and dividing by the time to complete
      the training session (joules of work per second). Data were also collected during
      the interset rest periods (heart rate [HR], respiratory rate [RR], and volume of
      oxygen consumed) and were used to explain why one rest strategy may positively
      impact work rate compared with another. Statistical analyses revealed significant
      differences (p <= 0.05) between the passive and active rest strategies, with the
      passive strategies allowing for improved work rate (supine = 62.77 +/- 7.32,
      seated = 63.66 +/- 8.37, and walking = 60.61 +/- 6.42 average joules of work per
      second). Results also suggest that the passive strategies resulted in superior
      HR, RR, and oxygen consumption recovery. In conclusion, work rate and
      physiological recovery were enhanced when supine and seated interset rest
      strategies were used compared with walking interset rest.

PMID- 25774624
TI  - Effect of Muscle-Damaging Eccentric Exercise on Running Kinematics and Economy
      for Running at Different Intensities.
AB  - The objective of this study was to explore the changes in running kinematics and
      economy during running at different intensities 1 and 24 hours after a muscle
      damaging bench-stepping exercise. Healthy, physically active adult women were
      recruited for this study. The subjects' running kinematics, heart rate, gas
      exchange, minute ventilation, and perceived exertion were continuously recorded
      during the increasing-intensity running test on a treadmill for different testing
      conditions: a control condition and 1 and 24 hours after the bench-stepping
      exercise test. Two muscle damage markers, muscle soreness and blood creatine
      kinase (CK) activity, were measured before and 24 hours after the stepping
      exercise. Muscle soreness and blood CK activity were significantly altered (exact
      p <= 0.05, Monte Carlo test) 24 hours after the bench-stepping exercise. The
      stride length, stride frequency, and support time at different running
      intensities did not change. Twenty-four hours after the previous step exercise,
      ankle dorsiflexion in the support phase was significantly higher during severe
      intensity running, the range of knee flexion at the stance phase was
      significantly lower during moderate-intensity running, and knee flexion at the
      end of the amortization phase was significantly lower during heavy-intensity
      running compared with the control values (exact p <= 0.05, Monte Carlo test). The
      running economy at moderate and heavy intensities, maximum ventilation, and
      maximum heart rate did not change. We conclude that, given moderate soreness in
      the calf muscles 24 hours after eccentric exercise, the running kinematics are
      slightly but significantly changed without a detectable effect on running
      economy.

PMID- 25774625
TI  - Acute Postexercise Time Course Responses of Hypertrophic vs. Power-Endurance
      Squat Exercise Protocols on Maximal and Rapid Torque of the Knee Extensors.
AB  - The aim of this study was to examine the effects of a medium-intensity high
      volume vs. explosive squat protocol on the postexercise time course responses of
      maximal and rapid strength of the knee extensors. Seventeen resistance-trained
      men (mean +/- SD: age = 22.0 +/- 2.6 years) performed maximal voluntary
      contractions (MVCs) of the knee extensors before and after performing a squat
      workout using either a low-intensity fast velocity (LIFV) (5 * 16 at 40% 1
      repetition maximum) or a traditional high-intensity slow velocity (TISV) (5 * 8
      at 80% 1RM) exercise protocol. For each MVC, peak torque (PT), peak rate of
      torque development (RTDpeak), absolute (RTDabs), and relative RTD (RTDnorm) at
      early (0-50 milliseconds) and late (100-200 milliseconds) phases of muscle
      contraction were examined at pre- (Pre) and post-exercise at 0, 7, 15, and 30
      (Post0...30) minutes. There were no intensity * time interactions for any
      variables (p = 0.098-0.832). Peak torque was greater at Pre than Post0 and Post7
      (p = 0.001-0.016) but was not greater than Post15 and Post30 (p = 0.010-0.189).
      RTDpeak and early absolute RTD (RTD50abs) were greater at Pre than all
      postexercise time phases (p = 0.001-0.050); however, later absolute RTD (RTD100
      200abs) was only greater at Pre than Post0 and Post30 (p = 0.013-0.048). Early
      relative RTD (RTD50norm) was only higher at Pre compared with Post0 (p = 0.023),
      whereas no differences were observed for later relative RTD (RTD100-200norm) (p =
      0.920-0.990). Low-intensity fast velocity and TISV squat protocols both yielded
      acute decreases in maximal and rapid strength capacities following free-weight
      squats, with rapid strength showing slower recovery characteristics than maximal
      strength.

PMID- 25774626
TI  - Influence of Dehydration on Intermittent Sprint Performance.
AB  - This study examined the effects of dehydration on intermittent sprint performance
      and perceptual responses. Eight male collegiate baseball players completed
      intermittent sprints either dehydrated (DEHY) by 3% body mass or euhydrated (EU).
      Body mass was reduced through exercise in the heat with controlled fluid
      restriction occurring 1 day before the trial. Participants completed twenty-four
      30-m sprints divided into 3 bouts of 8 sprints with 45 seconds of rest between
      each sprint and 3 minutes between each bout. Perceived recovery status (PRS)
      scale was recorded before the start of each trial. Heart rate (HR), ratings of
      perceived exertion (RPE) (0-10 OMNI scale), and perceived readiness (PR) scale
      were recorded after every sprint, and session RPE (SRPE) was recorded 20 minutes
      after completing the entire session. A 2 (condition) * 3 (bout of sprints)
      repeated-measures ANOVA revealed a significant main effect of condition on mean
      sprint time (p = 0.03), HR (p < 0.01), RPE (p = 0.01), and PR (p = 0.02). Post
      hoc tests showed significantly faster mean sprint times for EU vs. DEHY during
      the second (4.87 +/- 0.29 vs. 5.03 +/- 0.33 seconds; p = 0.01) and third bouts of
      sprints (4.91 +/- 0.29 vs. 5.12 +/- 0.44 seconds; p = 0.02). Heart rate was also
      significantly lower (p <= 0.05) for EU during the second and third bouts. Post
      hoc measures also showed significantly impaired (p <= 0.05) feelings of recovery
      (PRS) before exercise and increased (p <= 0.05) perceptual strain before each
      bout (PR) during the second and third bouts of repeated sprint work (i.e., RPE
      and PR) and after the total session (SRPE) in the DEHY condition. Dehydration
      impaired sprint performance, negatively altered perception of recovery status
      before exercise, and increased RPE and HR response.

PMID- 25774627
TI  - A New Submaximal Rowing Test to Predict 2,000-m Rowing Ergometer Performance.
AB  - The purpose of this study was to assess predictive value of a new submaximal
      rowing test (SmRT) on 2,000-m ergometer rowing time-trial performance in
      competitive rowers. In addition, the reliability of the SmRT was investigated.
      Twenty-four competitive male rowers participated in this study. After determining
      individual HRmax, all rowers performed an SmRT followed by a 2,000-m rowing
      ergometer time trial. In addition, the SmRT was performed 4 times (2 days in
      between) to determine the reliability. The SmRT consists of two 6-minute stages
      of rowing at 70 and 80% HRmax, followed by a 3-minute stage at 90% HRmax. Power
      was captured during the 3 stages, and 60 seconds of heart rate recovery (HRR60s)
      was measured directly after the third stage. Results showed that predictive value
      of power during the SmRT on 2,000-m rowing time also increased with stages.
      CVTEE% is 2.4, 1.9, and 1.3%. Pearson correlations (95% confidence interval [95%
      CI]) were -0.73 (-0.88 to -0.45), -0.80 (-0.94 to -0.67), and -0.93 (-0.97 to 
      0.84). 2,000-m rowing time and HRR60s showed no relationship. Reliability of
      power during the SmRT improved with the increasing intensity of the stages. The
      coefficient of variation (CVTEM%) was 9.2, 5.6, and 0.4%. Intraclass correlation
      coefficients (ICC) and 95% CI were 0.91 (0.78-0.97), 0.92 (0.81-0.97), and 0.99
      (0.97-1.00). The CVTEM% and ICC of HRR60s were 8.1% and 0.93 (0.82-0.98). In
      conclusion, the data of this study shows that the SmRT is a reliable test that it
      is able to accurately predict 2,000-m rowing time on an ergometer. The SmRT is a
      practical and valuable submaximal test for rowers, which can potentially assist
      with monitoring, fine-tuning and optimizing training prescription in rowers.

PMID- 25774628
TI  - Differences in End Range of Motion Vertical Jump Kinetic and Kinematic Strategies
      Between Trained Weightlifters and Elite Short Track Speed Skaters.
AB  - The purpose of this investigation was to identify differences in end range of
      motion (ROM) kinetic and kinematic strategies between highly resistance and
      vertical jump-trained athletes and controls. Weightlifters (WL: n = 4), short
      track speed skaters (STSS: n = 5), and nonresistance-trained controls (C: n = 6)
      performed 6 standing vertical squat jumps (SJ) and countermovement jumps (CMJ)
      without external resistance. Jump testing was performed using 3-dimensional
      marker trajectories captured with a 15-camera motion analysis system synchronized
      with 2 in-ground force plates. During SJ, there were large effects for the
      difference in time before toe off of peak vertical velocity between WL to STSS
      and C (ES: -1.43; ES: -1.73, respectively) and for the decrease between peak and
      toe off vertical velocity (ES: -1.28; ES: -1.71, respectively). During CMJ, there
      were large effects for the difference in time before toe off of peak vertical
      velocity between WL to STSS and C (ES: -1.28; ES: -1.53, respectively) and for
      decrease between peak and toe off vertical velocity (ES: -1.03; ES: -1.59,
      respectively). Accompanying these differences for both jump types were large
      effects for time of joint deceleration before toe off for all lower body joints
      between WL compared with C with large effects between WL and STSS at the hip and
      between STSS and C at the ankle. These findings suggest that the end ROM kinetic
      and kinematic strategy used during jumping is group-specific in power-trained
      athletes, with WL exhibiting superior strategies as compared with resistance- and
      jump-trained STSS.

PMID- 25774629
TI  - Thrombocytopenia as a predictor of severe acute kidney injury in patients with
      heat stroke.
AB  - BACKGROUND: Abnormalities of blood system often occur several days before acute
      kidney injury (AKI) in patients with heat stroke (HS). We aimed to investigate
      the prevalence and prognostic value of the early hematological markers in
      patients with AKI induced by HS. METHODS: In a retrospective cohort study, we
      analyzed the case records of 176 patients with HS and evaluated the hematological
      markers for early prediction and risk classification in the patients with AKI.
      RESULTS: Of 176, 103 (58%) HS cases developed AKI, and men comprised more than
      half (75%) of the sample population. The nadir platelet count significantly
      correlated with the levels of peak serum creatinine (r = -0.608, p < 0.01) and
      blood urea nitrogen (r = -0.546, p < 0.01), and the length of hospital stay (r = 
      0.393, p < 0.01). The areas under the receiver operating characteristic curves
      (AU-ROC) indicated the prognostic accuracy of hematological markers, AU-ROC was
      significantly higher with the nadir platelet count than that with the admission
      platelet count (AU-ROC of the nadir platelet: 0.73; 95% CI: 0.67-0.82; vs. AU-ROC
      of the admission platelet: 0.67; 95% CI: 0.59-0.75; p < 0.01). Multiple logistic
      regression results indicated that the nadir platelet count (adjusted ORs: 37.92;
      95% CI: 2.18-87.21; p < 0.01) was independent predictor of AKI in HS. CONCLUSION:
      The high mortality observed in HS complicated with AKI, and among the various
      hematological parameters assessed, thrombocytopenia is associated with AKI
      induced by HS independently.

PMID- 25774630
TI  - Severe serum amylase elevation, with only chronic kidney disease.

PMID- 25774631
TI  - Biases and regularities of grapheme-colour associations in Japanese
      nonsynaesthetic population.
AB  - Associations between graphemes and colours in a nonsynaesthetic Japanese
      population were investigated. Participants chose the most suitable colour from 11
      basic colour terms for each of 40 graphemes from the four categories of graphemes
      used in the Japanese language (kana characters, English alphabet letters, and
      Arabic and kanji numerals). This test was repeated after a three-week interval.
      In their responses, which were not as temporally consistent as those of grapheme
      colour synaesthetes, participants showed biases and regularities that were
      comparable to those of synaesthetes reported in past studies. Although it has
      been believed that only synaesthetes, and not nonsynaesthetes, tended to
      associate graphemes with colours based on grapheme frequency, Berlin and Kay's
      colour typology, and colour word frequency, participants in this study tended in
      part to associate graphemes with colours based on the above factors. Moreover,
      participants that were nonsynaesthetes tended to associate different graphemes
      that shared sounds and/or meanings (e.g., Arabic and kanji numerals representing
      the same number) with the same colours, which was analogous to the findings in
      Japanese synaesthetes. These results support the view that grapheme-colour
      synaesthesia might have its origins in cross-modal association processes that are
      shared with the general population. 

PMID- 25774633
TI  - Prevalence of IgG Antibodies against Human Papillomavirus (HPV) type 6, 11, 16,
      and 18 Virus-Like Particles in Women of Childbearing Age in Port Harcourt,
      Nigeria.
AB  - Most HPV prevalence studies have been carried out in high-resource countries with
      few studies focused on low-resource regions where highest HPV prevalence in the
      world occurs. This study reports on prevalence of IgG antibodies against HPVs
      among women of childbearing age in Port Harcourt, Nigeria. One hundred and eighty
      two consented women (age-range 19-45 years) were consecutively recruited.
      Demographic/behavioral data and 5 mL blood samples were collected from each
      woman. Plasma of each sample was assayed for HPV-6/11/16/18 virus-like particles
      using a HPV IgG ELISA kit. The overall anti-HPV prevalence was 4.9% while 7.7%
      with itching/wound in the private part tested positive. Most (88.9%) of the
      seropositive women were sexually active. Group-specific seropositivity was low
      (0.0-10.0%). It also showed that all the 9(100.0%) who tested positive to the HPV
      responded "yes" to no information on the source of HPV information. Being
      younger, married, high educational level, religion, and lack of information on
      HPV were the main correlates of HPV positivity among these women. None was
      vaccinated and would have been naturally exposed to at least one of HPV
      6/11/16/18. With 4.9% seropositivity and lack of information regarding HPV among
      these women, this study recommends a statewide enlightenment campaign and
      vaccination. 

PMID- 25774632
TI  - Arginine deprivation by arginine deiminase of Streptococcus pyogenes controls
      primary glioblastoma growth in vitro and in vivo.
AB  - Arginine auxotrophy constitutes a weak point of several tumors, among them
      glioblastoma multiforme (GBM). Hence, those tumors are supposed to be sensitive
      for arginine-depleting substances, such as arginine deiminase (ADI). Here we
      elucidated the sensitivity of patient-individual GBM cell lines toward
      Streptococcus pyogenes-derived ADI. To improve therapy, ADI was combined with
      currently established and pre-clinical cytostatic drugs. Additionally,
      effectiveness of local ADI therapy was determined in xenopatients. Half of the
      GBM cell lines tested responded well toward ADI monotherapy. In those cell lines,
      viability decreased significantly (up to 50%). Responding cell lines were
      subjected to combination therapy experiments to test if any additive or even
      synergistic effects may be achieved. Such promising results were obtained in 2/3
      cases. In cell lines HROG02, HROG05 and HROG10, ADI and Palomid 529 combinations
      were most effective yielding more than 70% killing after 2 rounds of treatment.
      Comparable boosted antitumoral effects were observed after adding chloroquine to
      ADI (>60% killing). Apoptosis, as well as cell cycle dysregulation were found to
      play a minor role. In some, but clearly not all cases, (epi-) genetic silencing
      of arginine synthesis pathway genes (argininosuccinate synthetase 1 and
      argininosuccinate lyase) explained obtained results. In vivo, ADI as well as the
      combination of ADI and SAHA efficiently controlled HROG05 xenograft growth,
      whereas adding Palomid 529 to ADI did not further increase the strong antitumoral
      effect of ADI. The cumulative in vitro and in vivo results proved ADI as a very
      promising candidate therapeutic, especially for development of adjuvant GBM
      combination treatments.

PMID- 25774634
TI  - Disordered selves or persons with schizophrenia?
AB  - PURPOSE OF REVIEW: This study builds on the self-disorder hypothesis of
      schizophrenia and further develops it by integrating the notion of 'selfhood'
      with that of 'personhood'. The self-disorder hypothesis brings to light the
      patient's subjective abnormal experiences. What may remain out of focus is the
      person's attitude towards these anomalous experiences. RECENT FINDINGS: Taking
      into account the notion of personhood allows for an articulation of the way the
      suffering person reflectively responds to and makes sense of her troubled
      selfhood. This approach is conducive to the development of a person-centred
      dialectical (PCD) model of schizophrenia that is concerned not only with the
      phenomenological description of troubled selfhood but also with how persons with
      schizophrenia interact and cope with their abnormal experiences. The principal
      clinical implication is the development of a two-tier descriptive system
      including phenomenal assessment of disordered selfhood and appraisal of personal
      background. SUMMARY: The recognition of the patient's resources is necessary for
      effective treatment, as recovery requires not only the reduction of full-blown
      symptoms but also a change in the patient's attitude with respect to her basic
      abnormal phenomena. The latter involves the person's own effort to make sense of
      and cope with her vulnerability.

PMID- 25774635
TI  - Effects of Korean Red Ginseng extract on hepatic lipid accumulation in HepG2
      cells.
AB  - In this study, we investigated the effects of Korean red ginseng water extract
      (KRGE) on hepatic lipid accumulation in HepG2 cells. KRGE decreased hepatic
      triglyceride and cholesterol levels. Further, KRGE suppressed expression of fatty
      acid synthase (FAS) and 3-hydroxy-3-methyl glutaryl coenzyme A (HMG-CoA)
      reductase. These results suggest that KRGE may reduce hepatic lipid accumulation
      by inhibition of FAS and HMG-CoA reductase expression in HepG2 cells. 

PMID- 25774636
TI  - Susceptibility to tuberculosis is associated with variants in the ASAP1 gene
      encoding a regulator of dendritic cell migration.
AB  - Human genetic factors predispose to tuberculosis (TB). We studied 7.6 million
      genetic variants in 5,530 people with pulmonary TB and in 5,607 healthy controls.
      In the combined analysis of these subjects and the follow-up cohort (15,087 TB
      patients and controls altogether), we found an association between TB and
      variants located in introns of the ASAP1 gene on chromosome 8q24 (P = 2.6 * 10(
      11) for rs4733781; P = 1.0 * 10(-10) for rs10956514). Dendritic cells (DCs)
      showed high ASAP1 expression that was reduced after Mycobacterium tuberculosis
      infection, and rs10956514 was associated with the level of reduction of ASAP1
      expression. The ASAP1 protein is involved in actin and membrane remodeling and
      has been associated with podosomes. The ASAP1-depleted DCs showed impaired matrix
      degradation and migration. Therefore, genetically determined excessive reduction
      of ASAP1 expression in M. tuberculosis-infected DCs may lead to their impaired
      migration, suggesting a potential mechanism of predisposition to TB.

PMID- 25774638
TI  - Psychometric properties of the Difficulties in Emotion Regulation Scale across
      demographic groups.
AB  - The Difficulties in Emotion Regulation Scale (DERS) is commonly used to assess
      difficulties recognizing and managing negative affect. Scores on the scale are
      strongly correlated with measures of psychopathology and are inversely correlated
      with measures of psychological well-being. Evidence supports the use of the DERS
      with adolescents and adults; to date, however, few studies have investigated the
      extent to which the psychometric properties of the DERS are consistent across
      demographic groups. The overarching goal of the present study was to examine the
      extent to which the factor structure of the DERS and the reliability and validity
      of DERS scores are consistent across gender and race in a diverse sample of
      adults. A total of 1,050 students from a medium-sized, urban university were
      included in the present study. Participants included 75.6% women and 24.4% men;
      42.5% of participants identified as Caucasian, 40.4% as African American, and
      17.1% as Asian American. Results showed that the DERS exhibits similar
      psychometric properties across men and women and all 3 racial groups that were
      included in this study. As such, the overall scale, as well as the original 6
      factor solution of the DERS, can be reliably applied to individuals from the
      demographic groups investigated in the current study, and results can be
      interpreted in accordance with those from the preliminary DERS validation sample.

PMID- 25774637
TI  - A recombined allele of the lipase gene CEL and its pseudogene CELP confers
      susceptibility to chronic pancreatitis.
AB  - Carboxyl ester lipase is a digestive pancreatic enzyme encoded by the CEL gene.
      Mutations in CEL cause maturity-onset diabetes of the young as well as pancreatic
      exocrine dysfunction. Here we describe a hybrid allele (CEL-HYB) originating from
      a crossover between CEL and its neighboring pseudogene, CELP. In a discovery
      series of familial chronic pancreatitis cases, we observed CEL-HYB in 14.1%
      (10/71) of cases compared to 1.0% (5/478) of controls (odds ratio (OR) = 15.5;
      95% confidence interval (CI) = 5.1-46.9; P = 1.3 * 10(-6) by two-tailed Fisher's
      exact test). In three replication studies of nonalcoholic chronic pancreatitis,
      we identified CEL-HYB in a total of 3.7% (42/1,122) cases and 0.7% (30/4,152)
      controls (OR = 5.2; 95% CI = 3.2-8.5; P = 1.2 * 10(-11); formal meta-analysis).
      The allele was also enriched in alcoholic chronic pancreatitis. Expression of CEL
      HYB in cellular models showed reduced lipolytic activity, impaired secretion,
      prominent intracellular accumulation and induced autophagy. These findings
      implicate a new pathway distinct from the protease-antiprotease system of
      pancreatic acinar cells in chronic pancreatitis.

PMID- 25774640
TI  - Development of a Short Form of the Five-Factor Narcissism Inventory: the FFNI-SF.
AB  - The Five-Factor Narcissism Inventory (FFNI; Glover, Miller, Lynam, Crego, &
      Widiger, 2012) is a 148-item self-report inventory of 15 traits designed to
      assess the basic elements of narcissism from the perspective of a 5-factor model.
      The FFNI assesses both vulnerable (i.e., cynicism/distrust, need for admiration,
      reactive anger, and shame) and grandiose (i.e., acclaim seeking, arrogance,
      authoritativeness, entitlement, exhibitionism, exploitativeness, grandiose
      fantasies, indifference, lack of empathy, manipulativeness, and thrill seeking)
      variants of narcissism. The present study reports the development of a short-form
      version of the FFNI in 4 diverse samples (i.e., 2 undergraduate samples, a sample
      recruited from MTurk, and a clinical community sample) using item response
      theory. The validity of the resultant 60-item short form was compared against the
      validity of the full scale in the 4 samples at both the subscale level and the
      level of the grandiose and vulnerable composites. Results indicated that the 15
      subscales remain relatively reliable, possess a factor structure identical to the
      structure of the long-form scales, and manifest correlational profiles highly
      similar to those of the long-form scales in relation to a variety of criterion
      measures, including basic personality dimensions, other measures of grandiose and
      vulnerable narcissism, and indicators of externalizing and internalizing
      psychopathology. Grandiose and vulnerable composites also behave almost
      identically across the short- and long-form versions. It is concluded that the
      FFNI-Short Form (FFNI-SF) offers a well-articulated assessment of the basic
      traits comprising grandiose and vulnerable narcissism, particularly when
      assessment time is limited.

PMID- 25774639
TI  - DISC Predictive Scales (DPS): Factor structure and uniform differential item
      functioning across gender and three racial/ethnic groups for ADHD, conduct
      disorder, and oppositional defiant disorder symptoms.
AB  - The factor structure and potential uniform differential item functioning (DIF)
      among gender and three racial/ethnic groups of adolescents (African American,
      Latino, White) were evaluated for attention deficit/hyperactivity disorder
      (ADHD), conduct disorder (CD), and oppositional defiant disorder (ODD) symptom
      scores of the DISC Predictive Scales (DPS; Leung et al., 2005; Lucas et al.,
      2001). Primary caregivers reported on DSM-IV ADHD, CD, and ODD symptoms for a
      probability sample of 4,491 children from three geographical regions who took
      part in the Healthy Passages study (mean age = 12.60 years, SD = 0.66).
      Confirmatory factor analysis indicated that the expected 3-factor structure was
      tenable for the data. Multiple indicators multiple causes (MIMIC) modeling
      revealed uniform DIF for three ADHD and 9 ODD item scores, but not for any of the
      CD item scores. Uniform DIF was observed predominantly as a function of child
      race/ethnicity, but minimally as a function of child gender. On the positive
      side, uniform DIF had little impact on latent mean differences of ADHD, CD, and
      ODD symptomatology among gender and racial/ethnic groups. Implications of the
      findings for researchers and practitioners are discussed.

PMID- 25774641
TI  - Communication preferences of chronically ill adolescents: development of an
      assessment instrument.
AB  - The purpose of this study was to develop and psychometrically test a patient
      oriented, theory-based questionnaire to capture the communication preferences of
      chronically ill adolescents in provider-patient interaction. In a qualitative
      prestudy, patients were asked to express their preferences in focus groups. From
      those results and relying on previous research findings, we generated
      questionnaire items and in a second pretest, examined them in 1-to-1 cognitive
      interviews for comprehensibility and acceptance. The resultant questionnaire was
      then psychometrically tested in the main study on 423 chronically ill inpatient
      adolescents aged 12 to 17 years in 14 rehabilitation clinics in Germany. Numerous
      preferences were extractable from the focus-group interviews and transferred into
      106 Items. Psychometric testing of the questionnaire resulted in 3 scales
      encompassing 27 items. These we describe as the emotional-affective communication
      component (EAC), instrumental communication component (IC), and adolescent
      specific communication component (ASC). Confirmatory factor analysis revealed the
      scales EAC und IC to be good to very good, and the ASC scale as satisfactory
      regarding unidimensionality. The participants gave the questionnaire high marks
      for comprehensibility, acceptance, and relevance. The 3 scales' Cronbach's alpha
      falls between .78 and .92. A questionnaire with 27 items is now available for
      application as a psychometrically tested and simple-to-use measuring instrument.
      Research is still needed concerning the generalizability to other patient groups
      (e.g., the acutely ill or outpatients) and whether it can be tailored for use by
      different types of care providers or to accommodate the communication preferences
      of parents.

PMID- 25774642
TI  - Digit Span is (mostly) related linearly to general intelligence: Every extra bit
      of span counts.
AB  - Historically, Digit Span has been regarded as a relatively poor indicator of
      general intellectual functioning (g). In fact, Wechsler (1958) contended that
      beyond an average level of Digit Span performance, there was little benefit to
      possessing a greater memory span. Although Wechsler's position does not appear to
      have ever been tested empirically, it does appear to have become clinical lore.
      Consequently, the purpose of this investigation was to test Wechsler's contention
      on the Wechsler Adult Intelligence Scale-Fourth Edition normative sample (N =
      1,800; ages: 16 - 69). Based on linear and nonlinear contrast analyses of means,
      as well as linear and nonlinear bifactor model analyses, all 3 Digit Span
      indicators (LDSF, LDSB, and LDSS) were found to exhibit primarily linear
      associations with FSIQ/g. Thus, the commonly held position that Digit Span
      performance beyond an average level is not indicative of greater intellectual
      functioning was not supported. The results are discussed in light of the
      increasing evidence across multiple domains that memory span plays an important
      role in intellectual functioning.

PMID- 25774644
TI  - Modeling the local potential at Pt nanoparticles in polymer electrolyte
      membranes.
AB  - We present a physical-analytical model for the potential distribution at Pt
      nanodeposits in a polymer electrolyte membrane (PEM). Experimental studies have
      shown that solid deposits of Pt in PEM play a dual role in radical-initiated
      membrane degradation. Surface reactions at Pt particles could facilitate the
      formation as well as the scavenging of ionomer-attacking radical species. The net
      radical balance depends on local equilibrium conditions at Pt nanodeposits in the
      PEM, specifically, their equivalent local electrode potential. Our approach
      utilizes a continuum description of crossover fluxes of reactant gases, coupled
      with the kinetics of electrochemical surface reactions at Pt nanodeposits to
      calculate the potential distribution. The local potential is a function of the
      PEM structure and composition, which is determined by PEM thickness,
      concentrations of H2 and O2, as well as the size and density distribution of Pt
      particles. Model results compare well with experimental data for the potential
      distribution in PEMs. 

PMID- 25774643
TI  - Psychometric properties of an innovative self-report measure: The Social Anxiety
      Questionnaire for adults.
AB  - This article presents the psychometric properties of a new measure of social
      anxiety, the Social Anxiety Questionnaire for adults (SAQ), composed of 30 items
      that were developed based on participants from 16 Latin American countries,
      Spain, and Portugal. Two groups of participants were included in the study: a
      nonclinical group involving 18,133 persons and a clinical group comprising 334
      patients with a diagnosis of social anxiety disorder (social phobia). Exploratory
      and confirmatory factor analyses supported a 5-factor structure of the
      questionnaire. The factors were labeled as follows: (1) Interactions with
      strangers, (2) Speaking in public/talking with people in authority, (3)
      Interactions with the opposite sex, (4) Criticism and embarrassment, and (5)
      Assertive expression of annoyance, disgust, or displeasure. Psychometric evidence
      supported the internal consistency, convergent validity, and measurement
      invariance of the SAQ. To facilitate clinical applications, a receiver operating
      characteristics (ROC) analysis identified cut scores for men and women for each
      factor and for the global score.

PMID- 25774646
TI  - Postcards in Persia: A Twelve to Twenty-four Month Follow-up of a Randomized
      Controlled Trial for Hospital-Treated Deliberate Self-Poisoning.
AB  - This study reports the outcomes, during follow-up, of a low-cost postcard
      intervention in a Randomized Control Trial of hospital-treated self-poisoning (n
      = 2300). The intervention was 9 postcards over 12 months (plus usual treatment)
      versus usual treatment. Three binary endpoints at 12-24 months (n = 2001) were:
      any suicidal ideation, suicide attempt, or self-cutting. There was a significant
      reduction in any suicidal ideation (RRR 0.20 CI 95% 0.13-0.27), (NNT 8, 6-13),
      and any suicide attempt (RRR 0.31, 0.06-0.50), (NNT 35, 19-195), in this non
      western population. However, there was no effect on self-cutting (RRR -0.01, 
      1.05-0.51). Sustained, brief contact by mail may reduce some forms of suicidal
      behavior in self-poisoning patients during the post intervention phase.

PMID- 25774647
TI  - Electrical control of Faraday rotation at a liquid-liquid interface.
AB  - A theory is developed for the Faraday rotation of light from a monolayer of
      charged magnetic nanoparticles at an electrified liquid-liquid interface. The
      polarization fields of neighboring nanoparticles enhance the Faraday rotation. At
      such interfaces, and for realistic sizes and charges of nanoparticles, their
      adsorption-desorption can be controlled with a voltage variation<1 V, providing
      electrovariable Faraday rotation. A calculation based on the Maxwell-Garnett
      theory predicts that the corresponding redistribution of 40 nm nanoparticles of
      yttrium iron garnet can switch a cavity with a quality factor larger than 10(4)
      for light of wavelength 500 nm at normal incidence.

PMID- 25774645
TI  - Trial of everolimus-eluting stents or bypass surgery for coronary disease.
AB  - BACKGROUND: Most trials comparing percutaneous coronary intervention (PCI) with
      coronary-artery bypass grafting (CABG) have not made use of second-generation
      drug-eluting stents. METHODS: We conducted a randomized noninferiority trial at
      27 centers in East Asia. We planned to randomly assign 1776 patients with
      multivessel coronary artery disease to PCI with everolimus-eluting stents or to
      CABG. The primary end point was a composite of death, myocardial infarction, or
      target-vessel revascularization at 2 years after randomization. Event rates
      during longer-term follow-up were also compared between groups. RESULTS: After
      the enrollment of 880 patients (438 patients randomly assigned to the PCI group
      and 442 randomly assigned to the CABG group), the study was terminated early
      owing to slow enrollment. At 2 years, the primary end point had occurred in 11.0%
      of the patients in the PCI group and in 7.9% of those in the CABG group (absolute
      risk difference, 3.1 percentage points; 95% confidence interval [CI], -0.8 to
      6.9; P=0.32 for noninferiority). At longer-term follow-up (median, 4.6 years),
      the primary end point had occurred in 15.3% of the patients in the PCI group and
      in 10.6% of those in the CABG group (hazard ratio, 1.47; 95% CI, 1.01 to 2.13;
      P=0.04). No significant differences were seen between the two groups in the
      occurrence of a composite safety end point of death, myocardial infarction, or
      stroke. However, the rates of any repeat revascularization and spontaneous
      myocardial infarction were significantly higher after PCI than after CABG.
      CONCLUSIONS: Among patients with multivessel coronary artery disease, the rate of
      major adverse cardiovascular events was higher among those who had undergone PCI
      with the use of everolimus-eluting stents than among those who had undergone
      CABG. (Funded by CardioVascular Research Foundation and others; BEST
      ClinicalTrials.gov number, NCT00997828.).

PMID- 25774648
TI  - Spontaneous resolution of a midtrimester dilated cervix with expectant management
      guided by quantitative foetal fibronectin results.

PMID- 25774649
TI  - A study of cellular counting to determine minimum thresholds for adequacy for
      liquid-based cervical cytology using a survey and counting protocol.
AB  - BACKGROUND: Liquid-based cytology (LBC) for cervical screening would benefit from
      laboratory practice guidelines that define specimen adequacy for reporting of
      slides. The evidence base required to define cell adequacy should incorporate
      both ThinPrepTM (TP; Hologic, Inc., Bedford, MA, USA) and SurePathTM (SP; BD
      Diagnostics, Burlington, NC, USA), the two LBC systems used in the UK cervical
      screening programmes. OBJECTIVES: The objectives of this study were to determine
      (1) current practice for reporting LBC in England, Wales and Scotland, (2) a
      reproducible method for cell counting, (3) the cellularity of slides classified
      as inadequate, negative or abnormal and (4) the impact of varying cellularity on
      the likelihood of detecting cytological abnormalities. DESIGN: The study involved
      four separate arms to pursue each of the four objectives. (1) A questionnaire
      survey of laboratories was conducted. (2) A standard counting protocol was
      developed and used by three experienced cytopathologists to determine a reliable
      and reproducible cell counting method. (3) Slide sets which included a range of
      cytological abnormalities were each sent to three laboratories for cell counting
      to study the correlation between cell counts and reported cytological outcomes.
      (4) Dilution of LBC samples by fluid only (unmixed) or by dilution with a sample
      containing normal cells (mixed) was performed to study the impact on reporting of
      reducing either the total cell count or the relative proportion of abnormal to
      normal cells. SETTING: The study was conducted within the cervical screening
      programmes in England, Wales and Scotland, using routinely obtained cervical
      screening samples, and in 56 participating NHS cervical cytology laboratories.
      PARTICIPANTS: The study involved only routinely obtained cervical screening
      samples. INTERVENTIONS: There was no clinical intervention. MAIN OUTCOME
      MEASURES: The main outcome measures were (1) reliability of counting method, (2)
      correlation of reported cytology grades with cellularity and (3) levels of
      detection of abnormal cells in progressively diluted cervical samples. RESULTS:
      Laboratory practice varied in terms of threshold of cellular adequacy and of
      morphological markers of adequacy. While SP laboratories generally used a minimum
      acceptable cell count (MACC) of 15,000, the MACC employed by TP laboratories
      varied between 5000 and 15,000. The cell counting study showed that a standard
      protocol achieved moderate to strong inter-rater reproducibility. Analysis of
      slide reporting from laboratories revealed that a large proportion of the samples
      reported as inadequate had cell counts above a threshold of 15,000 for SP, and
      5000 and 10,000 for TP. Inter-rater unanimity was greater among more cellular
      preparations. Dilution studies demonstrated greater detection of abnormalities in
      slides with counts above the MACC and among slides with more than 25 dyskaryotic
      cells. CONCLUSIONS: Variation in laboratory practice demonstrates a requirement
      for evidence-based standards for designating a MACC. This study has indicated
      that a MACC of 15,000 and 5000 for SP and TP, respectively, achieves a balance in
      terms of maintaining sensitivity and low inadequacy rates. FUTURE WORK: The
      findings of this study should inform the development of laboratory practice
      guidelines. FUNDING: The National Institute for Health Research Health Technology
      Assessment programme.

PMID- 25774650
TI  - Past and Present Insights on Alpha-linolenic Acid and the Omega-3 Fatty Acid
      Family.
AB  - Alpha-linolenic acid (ALA) is the parent essential fatty acid of the omega-3
      family. This family includes docosahexaenoic acid (DHA), which has been conserved
      in neural signaling systems in the cephalopods, fish, amphibian, reptiles, birds,
      mammals, primates, and humans. This extreme conservation, in spite of wide
      genomic changes of over 500 million years, testifies to the uniqueness of this
      molecule in the brain and affirms the importance of omega-3 fatty acids. While
      DHA and its close precursor, eicosapentaenoic acids (EPA), have received much
      attention by the research community, ALA, as the precursor of both, has been
      considered of little interest. There are many papers on ALA requirements in
      experimental animals. Unlike humans, rats and mice can readily convert ALA to EPA
      and DHA, so it is unclear whether the effect is solely due to the conversion
      products or to ALA itself. The intrinsic role of ALA has yet to be defined. This
      paper will discuss both recent and historical findings related to this
      distinctive group of fatty acids, and will highlight the physiological
      significance of the omega-3 family. 

PMID- 25774651
TI  - Harnessing the power of community-based participatory research: examining
      knowledge, action, and consciousness in the PROUD study.
AB  - Community-based participatory research (CBPR) is an approach to research that
      recognizes the specific knowledge and abilities that individuals from diverse
      backgrounds bring to the generation of new knowledge for the purpose of social
      action aimed at improving public health and health equity. In this article, the
      authors apply Gaventa and Cornwall's dimensions of participatory research to the
      analysis of 12 semistructured interviews with members of our Community Advisory
      Committee for the Participatory Research in Ottawa: Understanding Drugs (PROUD)
      study. This process-to-outcomes framework may help projects more systematically
      explore their experiences in relation to common CBPR principles and lead to
      greater conceptual clarity. 

PMID- 25774652
TI  - Bidirectional relationship between the body mass index and substance use in young
      men.
AB  - BACKGROUND: Obesity and substance use are major concern in young people. This
      study explored the bidirectional longitudinal relationships between the body mass
      index (BMI) of young men and their use of (1) 4 classes of nonmedical
      prescription drugs; (2) alcohol; (3) tobacco; and (4) cannabis. METHODS: Baseline
      and follow-up data from the Cohort Study on Substance Use Risk Factors were used
      (N = 5007). A cross-lagged panel model, complemented by probit models as
      sensitivity analysis, was run to determine the bidirectional relationships
      between BMI and substance use. Alcohol was assessed using risky single-occasion
      drinking (RSOD); tobacco, using daily smoking; and cannabis, using hazardous
      cannabis use (defined as twice-weekly or more cannabis use). Nonmedical
      prescription drugs use (NMPDU) included opioid analgesics, sedatives/sleeping
      pills, anxiolytics, and stimulants. RESULTS: Different associations were found
      between BMI and substance use. Only RSOD (beta = -.053, P = .005) and NMPDU of
      anxiolytics (beta = .040, P = .020) at baseline significantly predicted BMI at
      follow-up. Baseline RSOD predicted a lower BMI at follow-up, whereas baseline
      NMPDU of anxiolytics predicted higher BMI at follow-up. Furthermore, BMI at
      baseline significantly predicted daily smoking (beta = .050, P = .007) and
      hazardous cannabis use (beta = .058, P = .030). CONCLUSIONS: These results
      suggest different associations between BMI and the use of various substances by
      young men. However, only RSOD and NMPDU of anxiolytics predicted BMI, whereas BMI
      predicted daily smoking and hazardous cannabis use.

PMID- 25774653
TI  - Hysteresis in audiovisual synchrony perception.
AB  - The effect of stimulation history on the perception of a current event can yield
      two opposite effects, namely: adaptation or hysteresis. The perception of the
      current event thus goes in the opposite or in the same direction as prior
      stimulation, respectively. In audiovisual (AV) synchrony perception, adaptation
      effects have primarily been reported. Here, we tested if perceptual hysteresis
      could also be observed over adaptation in AV timing perception by varying
      different experimental conditions. Participants were asked to judge the synchrony
      of the last (test) stimulus of an AV sequence with either constant or gradually
      changing AV intervals (constant and dynamic condition, respectively). The onset
      timing of the test stimulus could be cued or not (prospective vs. retrospective
      condition, respectively). We observed hysteretic effects for AV synchrony
      judgments in the retrospective condition that were independent of the constant or
      dynamic nature of the adapted stimuli; these effects disappeared in the
      prospective condition. The present findings suggest that knowing when to estimate
      a stimulus property has a crucial impact on perceptual simultaneity judgments.
      Our results extend beyond AV timing perception, and have strong implications
      regarding the comparative study of hysteresis and adaptation phenomena. 

PMID- 25774654
TI  - Multilocus sequence typing and virulence gene profiles associated with
      Escherichia coli from human and animal sources.
AB  - We investigated whether specific sequence types, and their shared virulence gene
      profiles, may be associated with both human and food animal reservoirs. A total
      of 600 Escherichia coli isolates were assembled from human (n=265) and food
      animal (n=335) sources from overlapping geographic areas and time periods (2005
      2010) in Canada. The entire collection was subjected to multilocus sequence
      typing and a subset of 286 E. coli isolates was subjected to an E. coli-specific
      virulence gene microarray. The most common sequence type (ST) was E. coli ST10,
      which was present in all human and food-animal sources, followed by ST69, ST73,
      ST95, ST117, and ST131. A core group of virulence genes was associated with all
      10 common STs including artJ, ycfZ, csgA, csgE, fimA, fimH, gad, hlyE, ibeB,
      mviM, mviN, and ompA. STs 73, 92, and 95 exhibited the largest number of
      virulence genes, and all were exclusively identified from human infections. ST117
      was found in both human and food-animal sources and shared virulence genes common
      in extraintestinal pathogenic E. coli lineages. Select groups of E. coli may be
      found in both human and food-animal reservoirs.

PMID- 25774655
TI  - HPV knowledge and factors associated with intention to use condoms for reducing
      HPV infection risk among adolescent women in Taiwan.
AB  - Human papillomavirus (HPV) is a frequent cause of sexually transmitted infection
      worldwide, and has a key role in the etiology of cervical cancer. Young people
      are the most vulnerable age group for acquiring HPV infection, but this
      particular age group in Taiwan knows little about it. This study investigated
      Taiwanese adolescent women's knowledge of HPV and factors associated with
      intention to use condoms for reducing HPV-related diseases among adolescent
      women. A descriptive cross-sectional design was used, and a convenience sample of
      384 adolescent women aged 15 to 16 years in Southern Taiwan was recruited. Data
      were collected using a self-administered questionnaire and analyzed with
      descriptive statistics, t-test or ANOVA, and multiple regression analysis. Only
      26.6% of the participants were aware of HPV. The percentage of correct answers
      for knowledge about HPV was 35.4%. Factors associated with intention to use
      condoms for HPV prevention were discussion of sexual issues, attitude, subjective
      norm, perceived behavioral control, and HPV knowledge. These variables accounted
      for 55.8% of the variance in scores for intention to use condoms for HPV
      prevention. These findings could be used in future HPV prevention education and
      campaigns. Future intervention programs might be particularly focused on
      insufficient HPV knowledge among adolescent females. 

PMID- 25774657
TI  - Prevalence of obstructive sleep apnea syndrome and CPAP adherence in the elderly
      Chinese population.
AB  - BACKGROUND: This study assessed the prevalence of obstructive sleep apnea
      syndrome (OSAS) and CPAP adherence in the elderly Chinese in Hong Kong. METHODS:
      We conducted a sleep questionnaire survey among the elders aged >=60 years in the
      community centres followed by level 3 home sleep study (Embletta). Subjects with
      an apnea hypopnea index (AHI) >= 15/hr alone and those with AHI >= 5/hr plus
      either cardiovascular risk factors or Epworth Sleepiness Score (ESS) >= 10 were
      offered CPAP treatment. RESULTS: Altogether 819 subjects were interviewed with
      mean (SD) age of 73.9 (7.5) years, BMI 24.2 (3.6) kg/m2, neck circumference 34.9
      (3.4) cm and ESS 6.6 (5.2). Daytime sleepiness was reported by 72.4%, snoring
      loudly 5.1% and witnessed apnea 4%. Among 234 subjects who underwent home sleep
      study, 156 (66.7%), 102 (43.6%), 70 (29.9%) and 45 (19.2%) had AHI >= 5, >= 10,
      >= 15 and >= 20/hr respectively, with the prevalence increasing with age and BMI.
      In the sample, 149 subjects (63.7%) were classified as having OSAS, as defined by
      an AHI >= 5/hr with associated symptoms, involving 81 men (74.3%) and 68 women
      (54.4%). Neck circumference and snoring frequency were the only positive
      independent factors associated with the AHI and the diagnosis of OSAS. Among 141
      subjects who were offered CPAP treatment, 30 accepted CPAP prescription with
      improvement of ESS and cognitive function over 12 months with CPAP usage of 4.2
      (2.2) h/night. CONCLUSION: This study showed a high prevalence of OSAS among the
      community elders in Hong Kong. Home CPAP acceptance was low but there was
      significant improvement of subjective sleepiness and cognitive function among
      those on CPAP treatment.

PMID- 25774656
TI  - The Escherichia coli small protein MntS and exporter MntP optimize the
      intracellular concentration of manganese.
AB  - Escherichia coli does not routinely import manganese, but it will do so when iron
      is unavailable, so that manganese can substitute for iron as an enzyme cofactor.
      When intracellular manganese levels are low, the cell induces the MntH manganese
      importer plus MntS, a small protein of unknown function; when manganese levels
      are high, the cell induces the MntP manganese exporter and reduces expression of
      MntH and MntS. The role of MntS has not been clear. Previous work showed that
      forced MntS synthesis under manganese-rich conditions caused bacteriostasis. Here
      we find that when manganese is scarce, MntS helps manganese to activate a variety
      of enzymes. Its overproduction under manganese-rich conditions caused manganese
      to accumulate to very high levels inside the cell; simultaneously, iron levels
      dropped precipitously, apparently because manganese-bound Fur blocked the
      production of iron importers. Under these conditions, heme synthesis stopped,
      ultimately depleting cytochrome oxidase activity and causing the failure of
      aerobic metabolism. Protoporphyrin IX accumulated, indicating that the
      combination of excess manganese and iron deficiency had stalled ferrochelatase.
      The same chain of events occurred when mutants lacking MntP, the manganese
      exporter, were exposed to manganese. Genetic analysis suggested the possibility
      that MntS exerts this effect by inhibiting MntP. We discuss a model wherein
      during transitions between low- and high-manganese environments E. coli uses MntP
      to compensate for MntH overactivity, and MntS to compensate for MntP
      overactivity. 

PMID- 25774658
TI  - Quantification of a cardiac biomarker in human serum using extraordinary optical
      transmission (EOT).
AB  - Nanoimprinting lithography (NIL) is a manufacturing process that can produce
      macroscale surface areas with nanoscale features. In this paper, this technique
      is used to solve three fundamental issues for the application of localized
      surface plasmonic resonance (LSPR) in practical clinical measurements: assay
      sensitivity, chip-to-chip variance, and the ability to perform assays in human
      serum. Using NIL, arrays of 140 nm square features were fabricated on a sensing
      area of 1.5 mm x 1.5 mm with low cost. The high reproducibility of NIL allowed
      for the use of a one-chip, one-measurement approach with 12 individually
      manufactured surfaces with minimal chip-to-chip variations. To better approximate
      a real world setting, all chips were modified with a biocompatible, multi
      component monolayer and inter-chip variability was assessed by measuring a
      bioanalyte standard (2.5-75 ng/ml) in the presence of a complex biofluid, human
      serum. In this setting, nanoimprinted LSPR chips were able to provide sufficient
      characteristics for a 'low-tech' approach to laboratory-based bioanalyte
      measurement, including: 1) sufficient size to interface with a common laboratory
      light source and detector without the need for a microscope, 2) high sensitivity
      in serum with a cardiac troponin limit of detection of 0.55 ng/ml, and 3) very
      low variability in chip manufacturing to produce a figure of merit (FOM) of 10.5.
      These findings drive LSPR closer to technical comparability with ELISA-based
      assays while preserving the unique particularities of a LSPR based sensor,
      suitability for multiplexing and miniaturization, and point-of-care detections. 

PMID- 25774660
TI  - Patient Anxiety and Depression Moderate the Effects of Increased Self-management
      Knowledge on Physical Activity: A Secondary Analysis of a Randomised Controlled
      Trial on Health-Mentoring in COPD.
AB  - OBJECTIVE: Anxiety and depression are common comorbidities in people with chronic
      obstructive pulmonary disease (COPD). While these comorbidities could potentially
      lead to a higher motivation to learn about self-management, they could also
      inhibit patients from translating this knowledge into appropriate self-management
      behaviours. This paper explores the moderating effects of anxiety and depression
      on a health-mentoring intervention, focusing on mechanisms of change (mediation).
      METHODS: 182 COPD patients participated in an RCT, with anxiety and depression
      assessed by the Hospital Anxiety and Depression Scale (HADS), self-management
      knowledge by the Partners in Health Scale, and spontaneous physical activity
      using accelerometers, all measured at baseline, 6 and 12 months. The moderated
      mediation model tested the intervention's effect on physical activity, mediated
      via changes in self-management knowledge, at different levels of anxiety and
      depression. RESULTS: Knowledge mediated the effect of the intervention on changes
      in physical activity only for participants reporting low levels of anxiety or
      depression. Both acted as moderators: Increased knowledge led to more physical
      activity among participants reporting low anxiety or depression and to less
      activity among highly anxious or depressed participants. CONCLUSION: Although
      health-mentoring interventions can be an effective tool to increase knowledge and
      physical activity among COPD patients, it is essential to take anxiety and
      depression into account, as increased knowledge may have detrimental effects in
      highly anxious or depressed participants. This suggests that patients with
      elevated anxiety or depression may need to be treated appropriately before
      engaging in chronic disease self-management interventions.

PMID- 25774659
TI  - TFIIB is only ~9 A away from the 5'-end of a trimeric RNA primer in a functional
      RNA polymerase II preinitiation complex.
AB  - Recent X-ray crystallographic studies of Pol II in complex with the general
      transcription factor (GTF) IIB have begun to provide insights into the mechanism
      of transcription initiation. These structures have also shed light on the
      architecture of the transcription preinitiation complex (PIC). However,
      structural characterization of a functional PIC is still lacking, and even the
      topological arrangement of the GTFs in the Pol II complex is a matter of
      contention. We have extended our activity-based affinity crosslinking studies,
      initially developed to investigate the interaction of bacterial RNA polymerase
      with sigma, to the eukaryotic transcription machinery. Towards that end, we
      sought to identify GTFs that are within the Pol II active site in a functioning
      PIC. We provide biochemical evidence that TFIIB is located within ~9 A of the -2
      site of promoter DNA, where it is positioned to play a role in de novo
      transcription initiation. 

PMID- 25774661
TI  - The Internal Structure of Responses to the Trait Emotional Intelligence
      Questionnaire-Short Form: An Exploratory Structural Equation Modeling Approach.
AB  - Notwithstanding the wide use of the Trait Emotional Intelligence Questionnaire
      Short Form (TEIQue-SF) as a brief assessment of trait emotional intelligence
      (TEI), the psychometric properties of this measure have not been systematically
      examined. This article reports on research conducted to evaluate the latent
      structure underlying TEIQue-SF item data and test the gender invariance of scores
      as critical initial steps in determining the psychometric robustness of the
      inventory. In doing so, the article demonstrates an application of exploratory
      structural equation modeling as an alternative to the more restrictive
      independent clusters model of confirmatory factor analysis for examining
      factorially complex personality data. On the basis of 476 responses to the TEIQue
      SF, evidence was obtained for the multidimensionality of the inventory reflected
      in a retained correlated traits solution. Tests of gender invariance revealed
      equivalence of item factor loadings, intercepts, uniquenesses, correlated
      uniquenesses, and the factor variance-covariance matrix, but not latent means.
      Men were found to be moderately higher on self-control and sociability than
      women, whereas women scored marginally higher on emotionality than men. No
      significant gender differences were found on mean levels of well-being. The
      benefits of the multidimensionality of the TEIQue-SF, limitations of the study,
      and directions for future research are discussed. 

PMID- 25774662
TI  - Post-treatment vascular leakage and inflammatory responses around brain cysts in
      porcine neurocysticercosis.
AB  - Cysticidal treatment of neurocysticercosis, an infection of humans and pig brains
      with Taenia solium, results in an early inflammatory response directed to cysts
      causing seizures and focal neurological manifestations. Treatment-induced
      pericystic inflammation and its association with blood brain barrier (BBB)
      dysfunction, as determined by Evans blue (EB) extravasation, was studied in
      infected untreated and anthelmintic-treated pigs. We compared the magnitude and
      extent of the pericystic inflammation, presence of EB-stained capsules, the level
      of damage to the parasite, expression of genes for proinflammatory and regulatory
      cytokines, chemokines, and tissue remodeling by quantitative PCR assays between
      treated and untreated infected pigs and between EB-stained (blue) and non stained
      (clear) cysts. Inflammatory scores were higher in pericystic tissues from EB
      stained cysts compared to clear cysts from untreated pigs and also from
      anthelmintic-treated pigs 48 hr and 120 hr after treatment. The degree of
      inflammation correlated with the severity of cyst wall damage and both increased
      significantly at 120 hours. Expression levels of the proinflammatory genes for IL
      6, IFN-gamma, TNF-alpha were higher in EB-stained cysts compared to clear cysts
      and unaffected brain tissues, and were generally highest at 120 hr. Additionally,
      expression of some markers of immunoregulatory activity (IL-10, IL-2Ralpha) were
      decreased in EB-stained capsules. An increase in other markers for regulatory T
      cells (CTLA4, FoxP3) was found, as well as significant increases in expression of
      two metalloproteases, MMP1 and MMP2 at 48 hr and 120 hr post-treatment. We
      conclude that the increase in severity of the inflammation caused by treatment is
      accompanied by both a proinflammatory and a complex regulatory response, largely
      limited to pericystic tissues with compromised vascular integrity. Because
      treatment induced inflammation occurs in porcine NCC similar to that in human
      cases, this model can be used to investigate mechanisms involved in host damaging
      inflammatory responses and agents or modalities that may control damaging post
      treatment inflammation. 

PMID- 25774663
TI  - Deletion of Jun proteins in adult oligodendrocytes does not perturb cell
      survival, or myelin maintenance in vivo.
AB  - Oligodendrocytes, the myelin-forming glial cells of the central nervous system
      (CNS), are fundamental players in rapid impulse conduction and normal axonal
      functions. JunB and c-Jun are DNA-binding components of the AP-1 transcription
      factor, which is known to regulate different processes such as proliferation,
      differentiation, stress responses and death in several cell types, including
      cultured oligodendrocyte/lineage cells. By selectively inactivating Jun B and c
      Jun in myelinating oligodendrocytes in vivo, we generated mutant mice that
      developed normally, and within more than 12 months showed normal ageing and
      survival rates. In the adult CNS, absence of JunB and c-Jun from mature
      oligodendrocytes caused low-grade glial activation without overt signs of
      demyelination or secondary leukocyte infiltration into the brain. Even after
      exposure to toxic or autoimmune oligodendrocyte insults, signs of altered
      oligodendrocyte viability were mild and detectable only upon cuprizone treatment.
      We conclude that JunB and c-Jun expression in post-mitotic oligodendrocytes is
      mostly dispensable for the maintainance of white matter tracts throughout adult
      life, even under demyelinating conditions. 

PMID- 25774664
TI  - Differences in Cardiometabolic Risk between Insulin-Sensitive and Insulin
      Resistant Overweight and Obese Children.
AB  - BACKGROUND: It is known that 15-30% overweight/obese adults do not suffer
      cardiometabolic consequences. There is limited literature examining factors that
      can be used to assess cardiometabolic health in overweight/obese children. If
      such factors can be identified, they would aid in differentiating those most in
      need for aggressive management. METHODS: Baseline data from 7- to 12-year-old,
      overweight, and obese children enrolled in a weight management program at an
      urban hospital were analyzed. Homeostatic model assessment for insulin resistance
      (HOMA-IR) <2.6 was used to define insulin-sensitive and HOMA-IR >=2.6 was used to
      defined insulin-resistant participants. Demographics, physical activity measures,
      and cardiometabolic risk factors were compared between the two phenotypes. Odds
      ratios (ORs) examining the association between intermediate endpoints (metabolic
      syndrome [MetS], nonalcoholic fatty liver disease [NAFLD], systemic inflammation,
      and microalbuminuria) and the two metabolic phenotypes were evaluated. RESULTS:
      Of the 362 overweight/obese participants, 157 (43.5%) were insulin sensitive and
      204 (56.5%) were insulin resistant. Compared to the insulin-sensitive group, the
      insulin-resistant group was older (8.6+/-1.6 vs. 9.9+/-1.7; p<0.001) and had a
      higher BMI z-score (1.89+/-0.42 vs. 2.04+/-0.42; p=0.001). After multivariable
      adjustment, compared to the insulin-sensitive group, the insulin-resistant group
      had higher odds of having MetS (OR, 5.47; 95% confidence interval [CI]: 1.72,
      17.35; p=0.004) and NAFLD (OR, 8.66; 95% CI, 2.48, 30.31; p=0.001), but not
      systemic inflammation (OR, 1.06; 95% CI: 0.56, 2.03; p=0.86) or microalbuminuria
      (OR, 1.71; 95% CI, 0.49, 6.04; p=0.403). CONCLUSIONS: Using a HOMA-IR value of
      >=2.6, clinical providers can identify prepubertal and early pubertal children
      most at risk. Focusing limited resources on aggressive weight interventions may
      lead to improvement in cardiometabolic health.

PMID- 25774666
TI  - Unraveling the Link Between Ectodermal Disorders and Primary Immunodeficiencies.
AB  - Primary immunodeficiencies (PIDs) include a heterogeneous group of mostly
      monogenic diseases characterized by functional/developmental alterations of the
      immune system. Skin and skin annexa abnormalities may be a warning sign of
      immunodeficiency, since both epidermal and thymic epithelium have ectodermal
      origin. In this review, we will focus on the most common immune disorders
      associated with ectodermal alterations. Elevated IgE levels represent the
      immunological hallmark of hyper-IgE syndrome, characterized by severe eczema and
      susceptibility to infections. Ectodermal dysplasia (ED) is a group of rare
      disorders that affect tissues of ectodermal origin. Hypoidrotic ED (HED), the
      most common form, is inherited as autosomal dominant, autosomal recessive or X
      linked trait (XLHED). HED and XLHED are caused by mutations in NEMO and EDA-1
      genes, respectively, and show similarities in the cutaneous involvement but
      differences in the susceptibility to infections and immunological phenotype.
      Alterations in the transcription factor FOXN1 gene, expressed in the mature
      thymic and skin epithelia, are responsible for human and murine athymia and
      prevent the development of the T-cell compartment associated to ectodermal
      abnormalities such as alopecia and nail dystrophy. The association between
      developmental abnormalities of the skin and immunodeficiencies suggest a role of
      the skin as a primary lymphoid organ. Recently, it has been demonstrated that a
      co-culture of human skin-derived keratinocytes and fibroblasts, in the absence of
      thymic components, can support the survival of human haematopoietic stem cells
      and their differentiation into T-lineage committed cells. 

PMID- 25774665
TI  - A membrane-type-1 matrix metalloproteinase (MT1-MMP)-discoidin domain receptor 1
      axis regulates collagen-induced apoptosis in breast cancer cells.
AB  - During tumour dissemination, invading breast carcinoma cells become confronted
      with a reactive stroma, a type I collagen-rich environment endowed with anti
      proliferative and pro-apoptotic properties. To develop metastatic capabilities,
      tumour cells must acquire the capacity to cope with this novel microenvironment.
      How cells interact with and respond to their microenvironment during cancer
      dissemination remains poorly understood. To address the impact of type I collagen
      on the fate of tumour cells, human breast carcinoma MCF-7 cells were cultured
      within three-dimensional type I collagen gels (3D COL1). Using this experimental
      model, we have previously demonstrated that membrane type-1 matrix
      metalloproteinase (MT1-MMP), a proteinase overexpressed in many aggressive
      tumours, promotes tumour progression by circumventing the collagen-induced up
      regulation of BIK, a pro-apoptotic tumour suppressor, and hence apoptosis. Here
      we performed a transcriptomic analysis to decipher the molecular mechanisms
      regulating 3D COL1-induced apoptosis in human breast cancer cells. Control and
      MT1-MMP expressing MCF-7 cells were cultured on two-dimensional plastic plates or
      within 3D COL1 and a global transcriptional time-course analysis was performed.
      Shifting the cells from plastic plates to 3D COL1 activated a complex
      reprogramming of genes implicated in various biological processes. Bioinformatic
      analysis revealed a 3D COL1-mediated alteration of key cellular functions
      including apoptosis, cell proliferation, RNA processing and cytoskeleton
      remodelling. By using a panel of pharmacological inhibitors, we identified
      discoidin domain receptor 1 (DDR1), a receptor tyrosine kinase specifically
      activated by collagen, as the initiator of 3D COL1-induced apoptosis. Our data
      support the concept that MT1-MMP contributes to the inactivation of the DDR1-BIK
      signalling axis through the cleavage of collagen fibres and/or the alteration of
      DDR1 receptor signalling unit, without triggering a drastic remodelling of the
      transcriptome of MCF-7 cells. 

PMID- 25774668
TI  - Individuals Are Continents; or, Why It's Time to Retire the Island Approach to
      Addiction.
AB  - Individuals are not island isolates. This is an old insight that finds expression
      in indigenous worldviews, ancient philosophies, religious doctrine, and modern
      social theories. Even so, science remains encumbered by the false dichotomies and
      reductionism inherited from the capitalist revolution and reinforced by the
      fragmentation of modern life. This same heritage encumbers addiction research and
      efforts to devise effective interventions. It does so because the island concept
      at its core filters out the most decisive factors contributing to addiction. We
      therefore recommend its replacement with what we call the continental concept of
      the individual, which conceives of society and the natural environment as
      extensions of individual corporeal bodies. Such a theoretical reorientation has
      significant implications for intervention research and practice. More
      specifically, it radically expands the scope of what constitutes a valid
      intervention in the first place. We call this reorientation the continental
      approach to drug addiction. 

PMID- 25774667
TI  - Physiologic concentrations of HMGB1 have no impact on cytokine-mediated
      eosinophil survival or chemotaxis in response to Eotaxin-2 (CCL24).
AB  - HMGB1 is an alarmin that can stimulate the innate immune system alone or in a
      complex with other inflammatory mediators. Given the recent interest in HMGB1
      with respect to the pathogenesis of eosinophil-associated disorders, including
      asthmatic inflammation and chronic rhinosinusitis, we have explored the role of
      this mediator and in promoting eosinophil activation. HMGB1 receptors RAGE and
      TLR4 but not TLR2 were detected on freshly isolated human eosinophils from
      healthy donors. Physiologic and relevant pathophysiologic levels of biologically
      active HMGB1 had no effect on survival of human eosinophils alone or in
      combination with pro-survival cytokines IL-5, IL-3, or GM-CSF, and increasing
      concentrations of HMGB1 had no impact on surface expression of RAGE, TLR2 or
      TLR4. Similarly, HMGB1 did not elicit chemotaxis of human eosinophils alone and
      had no effect in combination with the eosinophil chemotactic agent, eotaxin-2
      (CCL24). However, surface expression of TLR2 and TLR4 increased in response to
      cell stress, notably on eosinophils that remain viable after 48 hours without IL
      5. As such, HMGB1 signaling on eosinophils may be substantially more detailed,
      and may involve complex immunostimulatory pathways other than or in addition to
      those evaluated here. 

PMID- 25774669
TI  - Down-regulation of deacetylase HDAC6 inhibits the melanoma cell line A375.S2
      growth through ROS-dependent mitochondrial pathway.
AB  - Previous studies have shown that histone deacetylase 6 (HDAC6) plays critical
      roles in many cellular processes related to cancer. However, its biological roles
      in the development of melanoma remain unexplored. Our aim was to investigate
      whether HDAC6 has a biological role in human melanoma development and to
      understand its underlying mechanism. In the present study, HDAC6 expression was
      up-regulated in melanoma tissues and cell lines. Knockdown of HDAC6 significantly
      inhibited the proliferation and colony formation ability of A375.S2 cells,
      promoted cell arrest at G0/G1 phase and apoptosis. Additionally, western blotting
      assay showed that HDAC6 silencing suppressed Bcl-2 level and enhanced Bax level,
      then activated caspase-9 and caspase-3, and further activated the release of
      cytochrome c from mitochondria to cytoplasm, finally induced cell apoptosis
      involving the mitochondrial pathway. Knockdown of HDAC6 triggered a significant
      generation of ROS and disruption of mitochondrial membrane potential (MMP).
      Furthermore, ROS inhibitor, NAC reduced HDAC6 siRNA-induced ROS production, and
      blocked HDAC6 siRNA-induced loss of MMP and apoptosis. NAC also significantly
      blocked HDAC6 siRNA-induced mtDNA copy number decrease and mitochondrial
      biogenesis and degradation imbalance. In conclusion, the results showed that
      knockdown of HDAC6 induced apoptosis in human melanoma A375.S2 cells through a
      ROS-dependent mitochondrial pathway. 

PMID- 25774670
TI  - Temporal patterns of ant diversity across a mountain with climatically
      contrasting aspects in the tropics of Africa.
AB  - Factors that drive species richness over space and time are still poorly
      understood and are often context specific. Identifying these drivers for ant
      diversity has become particularly relevant within the context of contemporary
      global change events. We report on a long-term bi-annual (wet and dry seasons),
      standardized sampling of epigeal ants over a five year period on the mesic and
      arid aspects of an inselberg (Soutpansberg Mountain Range) in the tropics of
      Africa. We detail seasonal, annual and long-term trends of species density, test
      the relative contribution of geometric constraints, energy, available area,
      climate, local environmental variables, time, and space in explaining ant species
      density patterns through Generalized Linear Mixed Models (GLMM) where replicates
      were included as random factors to account for temporal pseudo-replication.
      Seasonal patterns were very variable and we found evidence of decreased seasonal
      variation in species density with increased elevation. The extent and
      significance of a decrease in species density with increased elevation varied
      with season. Annual patterns point to an increase in ant diversity over time. Ant
      density patterns were positively correlated with mean monthly temperature but
      geometric constraints dominated model performance while soil characteristics were
      minor correlates. These drivers and correlates accounted for all the spatio
      temporal variability in the database. Ant diversity was therefore mainly
      determined by geometric constraints and temperature while soil characteristics
      (clay and carbon content) accounted for smaller but significant amounts of
      variation. This study documents the role of season, elevation and their
      interaction in affecting ant species densities while highlighting the importance
      of neutral processes and temperature in driving these patterns. 

PMID- 25774671
TI  - Confident site localization using a simulated phosphopeptide spectral library.
AB  - We have investigated if phosphopeptide identification and simultaneous site
      localization can be achieved by spectral library searching. This allows taking
      advantage of comparison of specific spectral features, which would lead to
      improved discrimination of differential localizations. For building a library, we
      propose a spectral simulation strategy where all possible single phosphorylations
      can be simply and accurately (re)constructed on enzymatically dephosphorylated
      peptides, by predicting the diagnostic fragmentation events produced in beam-type
      CID. To demonstrate the performance of our approach, enriched HeLa
      phosphopeptides were dephosphorylated with alkaline phosphatase and analyzed with
      higher energy collisional dissociation (HCD), which were then used for creating a
      spectral library of simulated phosphopeptides. Spectral library searching using
      SpectraST was performed on data sets of synthetic phosphopeptides and the HeLa
      phosphopeptides, and subsequently compared to Mascot and Sequest database
      searching followed by phosphoRS and Ascore afforded localization, respectively.
      Our approach successfully led to accurate localization, and it outperformed other
      methods, when phosphopeptides were covered by the library. These results suggest
      that the searching with simulated spectral libraries serves as a crucial approach
      for both supplementing and validating the phosphorylation sites obtained by
      database searching and localization tools. For future development, simulation of
      multiply phosphorylated peptides remains to be implemented. 

PMID- 25774673
TI  - Autonomic molecular transport by polymer films containing programmed chemical
      potential gradients.
AB  - Materials which induce molecular motion without external input offer unique
      opportunities for spatial manipulation of molecules. Here, we present the use of
      polyacrylamide hydrogel films containing built-in chemical gradients (enthalpic
      gradients) to direct molecular transport. Using a cationic tertiary amine
      gradient, anionic molecules were directionally transported up to several
      millimeters. A 40-fold concentration of anionic molecules dosed in aerosol form
      on a substrate to a small region at the center of a radially symmetric cationic
      gradient was observed. The separation of mixtures of charged dye molecules was
      demonstrated using a boronic acid-to-cationic gradient where one molecule was
      attracted to the boronic acid end of the gradient, and the other to the cationic
      end of the gradient. Theoretical and computational analysis provides a
      quantitative description of such anisotropic molecular transport, and reveals
      that the gradient-imposed drift velocity is in the range of hundreds of
      nanometers per second, comparable to the transport velocities of biomolecular
      motors. This general concept of enthalpy gradient-directed molecular transport
      should enable the autonomous processing of a diversity of chemical species. 

PMID- 25774672
TI  - Complete chloroplast genome of the multifunctional crop globe artichoke and
      comparison with other Asteraceae.
AB  - With over 20,000 species, Asteraceae is the second largest plant family. High
      throughput sequencing of nuclear and chloroplast genomes has allowed for a better
      understanding of the evolutionary relationships within large plant families.
      Here, the globe artichoke chloroplast (cp) genome was obtained by a combination
      of whole-genome and BAC clone high-throughput sequencing. The artichoke cp genome
      is 152,529 bp in length, consisting of two single-copy regions separated by a
      pair of inverted repeats (IRs) of 25,155 bp, representing the longest IRs found
      in the Asteraceae family so far. The large (LSC) and the small (SSC) single-copy
      regions span 83,578 bp and 18,641 bp, respectively. The artichoke cp sequence was
      compared to the other eight Asteraceae complete cp genomes available, revealing
      an IR expansion at the SSC/IR boundary. This expansion consists of 17 bp of the
      ndhF gene generating an overlap between the ndhF and ycf1 genes. A total of 127
      cp simple sequence repeats (cpSSRs) were identified in the artichoke cp genome,
      potentially suitable for future population studies in the Cynara genus. Parsimony
      informative regions were evaluated and allowed to place a Cynara species within
      the Asteraceae family tree. The eight most informative coding regions were also
      considered and tested for "specific barcode" purpose in the Asteraceae family.
      Our results highlight the usefulness of cp genome sequencing in exploring plant
      genome diversity and retrieving reliable molecular resources for phylogenetic and
      evolutionary studies, as well as for specific barcodes in plants. 

PMID- 25774674
TI  - Thermal and hydrodynamic environments mediate individual and aggregative feeding
      of a functionally important omnivore in reef communities.
AB  - In eastern Canada, the destruction of kelp beds by dense aggregations (fronts) of
      the omnivorous green sea urchin, Strongylocentrotus droebachiensis, is a key
      determinant of the structure and dynamics of shallow reef communities. Recent
      studies suggest that hydrodynamic forces, but not sea temperature, determine the
      strength of urchin-kelp interactions, which deviates from the tenets of the
      metabolic theory of ecology (MTE). We tested the hypothesis that water
      temperature can predict short-term kelp bed destruction by S. droebachiensis in
      calm hydrodynamic environments. Specifically, we experimentally determined
      relationships among water temperature, body size, and individual feeding in the
      absence of waves, as well as among wave velocity, season, and aggregative
      feeding. We quantified variation in kelp-bed boundary dynamics, sea temperature,
      and wave height over three months at one subtidal site in Newfoundland to test
      the validity of thermal tipping ranges and regression equations derived from
      laboratory results. Consistent with the MTE, individual feeding during early
      summer (June-July) obeyed a non-linear, size- and temperature-dependent
      relationship: feeding in large urchins was consistently highest and positively
      correlated with temperature <12 degrees C and dropped within and above the 12-15
      degrees C tipping range. This relationship was more apparent in large than small
      urchins. Observed and expected rates of kelp loss based on sea temperature and
      urchin density and size structure at the front were highly correlated and
      differed by one order of magnitude. The present study speaks to the importance of
      considering body size and natural variation in sea temperature in studies of
      urchin-kelp interactions. It provides the first compelling evidence that sea
      temperature, and not only hydrodynamic forces, can predict kelp bed destruction
      by urchin fronts in shallow reef communities. Studying urchin-seaweed-predator
      interactions within the conceptual foundations of the MTE holds high potential
      for improving capacity to predict and manage shifts in marine food web structure
      and productivity. 

PMID- 25774675
TI  - Alexander Robertson (1834-1908): Glasgow's pioneer aphasiologist and
      epileptologist.
AB  - Alexander Robertson (1834-1908) was a Glasgow physician whose professional career
      was involved mainly with institutional-based practice but who published
      significant insights into the anatomical background to aphasia (1867) and the
      mechanisms of focal epileptogenesis (1869). His aphasiology ideas, including his
      suggestion that disconnection between cerebral centers involved in speech was
      responsible for the phenomenon, made him one of the earliest members of the late
      nineteenth-century school of aphasia diagram makers. His view of epileptogenesis
      was that contralateral convulsing arose from irritation in a local area of
      pathology on the surface of the cerebral cortex after the irritation spread to a
      cortical motor center and then down the motor pathway to the striatum, while
      spreading within the cortex itself caused loss of consciousness. This
      interpretation contains much of the essence of the present-day understanding of
      cortical epileptogenesis. The origin of this interpretation is often attributed
      to John Hughlings Jackson, but Robertson published the idea in full a year or two
      prior to Jackson. However, Robertson's original insights were hardly noticed at
      the time they were published and have since almost entirely been ignored. 

PMID- 25774676
TI  - The effect of single or repeated home visits on the hanging and use of
      insecticide-treated mosquito nets following a mass distribution campaign--a
      cluster randomized, controlled trial.
AB  - BACKGROUND: Study objective was to evaluate the effectiveness of commonly used
      post-campaign hang-up visits on the hanging and use of campaign nets. METHODS: A
      cluster-randomized trial was carried out in Uganda following an ITN distribution
      campaign. Five clusters (parishes, consisting of ~11 villages each) were randomly
      selected for each of the three study arms with between 7,534 and 9,401 households
      per arm. Arm 1 received one hang-up visit, while Arm 2 received two visits by
      volunteers four and seven months after the campaign. Visits consisted of
      assistance hanging the net and education on net use. The control arm was only
      exposed to messages during the campaign itself. Three cross-sectional surveys
      with a two-stage cluster sampling design, representative of the study
      populations, were carried out to capture the two key outcome variables of net
      hanging and ITN use. Sample size was calculated to detect at least a 15
      percentage-points change in net use, and was 1811 at endline. The analysis used
      an intention-to-treat approach. FINDINGS: Both hanging and use of ITN increased
      during follow-up in a similar way in all three study arms. The proportion of the
      population using an ITN the previous night was 64.0% (95% CI 60.8, 67.2), for one
      additional visit, 68.2% (63.8, 72.2) for two visits and 64.0% (59.4, 68.5) for
      the control. The proportion of households with all campaign nets hanging
      increased from 55.7% to 72.5% at endline (p<0.0005 for trend), with no difference
      between study arms. Financial cost per household visited was estimated as USD
      2.33 for the first visit and USD 2.24 for the second. CONCLUSIONS: Behavior
      change communication provided during the campaign or through other channels was
      sufficient to induce high levels of net hanging and use and additional "hang-up"
      activities were not cost-effective.

PMID- 25774677
TI  - How much does it cost to improve access to voluntary medical male circumcision
      among high-risk, low-income communities in Uganda?
AB  - BACKGROUND: The Ugandan Ministry of Health has endorsed voluntary medical male
      circumcision as an HIV prevention strategy and has set ambitious goals (e.g., 4.2
      million circumcisions by 2015). Innovative strategies to improve access for hard
      to reach, high risk, and poor populations are essential for reaching such goals.
      In 2009, the Makerere University Walter Reed Project began the first facility
      based VMMC program in Uganda in a non-research setting. In addition, a mobile
      clinic began providing VMMC services to more remote, rural locations in 2011. The
      primary objective of this study was to estimate the average cost of performing
      VMMCs in the mobile clinic compared to those performed in health facilities
      (fixed sites). The difference between such costs is the cost of improving access
      to VMMC. METHODS: A micro-costing approach was used to estimate costs from the
      service provider's perspective of a circumcision. Supply chain and higher-level
      program support costs are not included. RESULTS: The average cost (US$2012) of
      resources used per circumcision was $61 in the mobile program ($72 for more
      remote locations) compared to $34 at the fixed site. Costs for community
      mobilization, HIV testing, the initial medical exam, and staff for performing
      VMMC operations were similar for both programs. The cost of disposable surgical
      kits, the additional upfront cost for the mobile clinic, and additional costs for
      staff drive the differences in costs between the two programs. Cost estimates are
      relatively insensitive to patient flow over time. CONCLUSION: The MUWRP VMMC
      program improves access for hard to reach, relatively poor, and high-risk rural
      populations for a cost of $27-$38 per VMMC. Costs to patients to access services
      are almost certainly less in the mobile program, by reducing out-of-pocket travel
      expenses and lost time and associated income, all of which have been shown to be
      barriers for accessing treatment.

PMID- 25774678
TI  - Patterns and emerging trends in global ocean health.
AB  - International and regional policies aimed at managing ocean ecosystem health need
      quantitative and comprehensive indices to synthesize information from a variety
      of sources, consistently measure progress, and communicate with key
      constituencies and the public. Here we present the second annual global
      assessment of the Ocean Health Index, reporting current scores and annual changes
      since 2012, recalculated using updated methods and data based on the best
      available science, for 221 coastal countries and territories. The Index measures
      performance of ten societal goals for healthy oceans on a quantitative scale of
      increasing health from 0 to 100, and combines these scores into a single Index
      score, for each country and globally. The global Index score improved one point
      (from 67 to 68), while many country-level Index and goal scores had larger
      changes. Per-country Index scores ranged from 41-95 and, on average, improved by
      0.06 points (range -8 to +12). Globally, average scores increased for individual
      goals by as much as 6.5 points (coastal economies) and decreased by as much as
      1.2 points (natural products). Annual updates of the Index, even when not all
      input data have been updated, provide valuable information to scientists, policy
      makers, and resource managers because patterns and trends can emerge from the
      data that have been updated. Changes of even a few points indicate potential
      successes (when scores increase) that merit recognition, or concerns (when scores
      decrease) that may require mitigative action, with changes of more than 10-20
      points representing large shifts that deserve greater attention. Goal scores
      showed remarkably little covariance across regions, indicating low redundancy in
      the Index, such that each goal delivers information about a different facet of
      ocean health. Together these scores provide a snapshot of global ocean health and
      suggest where countries have made progress and where a need for further
      improvement exists. 

PMID- 25774679
TI  - Is the desire for status a fundamental human motive? A review of the empirical
      literature.
AB  - The current review evaluates the status hypothesis, which states that that the
      desire for status is a fundamental motive. Status is defined as the respect,
      admiration, and voluntary deference individuals are afforded by others. It is
      distinct from related constructs such as power, financial success, and social
      belongingness. A review of diverse literatures lent support to the status
      hypothesis: People's subjective well-being, self-esteem, and mental and physical
      health appear to depend on the level of status they are accorded by others.
      People engage in a wide range of goal-directed activities to manage their status,
      aided by myriad cognitive, behavioral, and affective processes; for example, they
      vigilantly monitor the status dynamics in their social environment, strive to
      appear socially valuable, prefer and select social environments that offer them
      higher status, and react strongly when their status is threatened. The desire for
      status also does not appear to be a mere derivative of the need to belong, as
      some theorists have speculated. Finally, the importance of status was observed
      across individuals who differed in culture, gender, age, and personality,
      supporting the universality of the status motive. Therefore, taken as a whole,
      the relevant evidence suggests that the desire for status is indeed fundamental.

PMID- 25774681
TI  - Correction to "Positive allostery in metal ion binding by a cooperatively folded
      beta-peptide bundle".

PMID- 25774680
TI  - Whole-genome analysis revealed the positively selected genes during the
      differentiation of indica and temperate japonica rice.
AB  - To investigate the selective pressures acting on the protein-coding genes during
      the differentiation of indica and japonica, all of the possible orthologous genes
      between the Nipponbare and 93-11 genomes were identified and compared with each
      other. Among these genes, 8,530 pairs had identical sequences, and 27,384 pairs
      shared more than 90% sequence identity. Only 2,678 pairs of genes displaying a
      Ka/Ks ratio significantly greater than one were revealed, and most of these genes
      contained only nonsynonymous sites. The genes without synonymous site were
      further analyzed with the SNP data of 1529 O. sativa and O. rufipogon accessions,
      and 1068 genes were identified to be under positive selection during the
      differentiation of indica and temperate japonica. The positively selected genes
      (PSGs) are unevenly distributed on 12 chromosomes, and the proteins encoded by
      the PSGs are dominant with binding, transferase and hydrolase activities, and
      especially enriched in the plant responses to stimuli, biological regulations,
      and transport processes. Meanwhile, the most PSGs of the known function and/or
      expression were involved in the regulation of biotic/abiotic stresses. The
      evidence of pervasive positive selection suggested that many factors drove the
      differentiation of indica and japonica, which has already started in wild rice
      but is much lower than in cultivated rice. Lower differentiation and less PSGs
      revealed between the Or-It and Or-IIIt wild rice groups implied that artificial
      selection provides greater contribution on the differentiation than natural
      selection. In addition, the phylogenetic tree constructed with positively
      selected sites showed that the japonica varieties exhibited more diversity than
      indica on differentiation, and Or-III of O. rufipogon exhibited more than Or-I. 

PMID- 25774682
TI  - Identification of alcohol conformers by Raman spectra in the C-H stretching
      region.
AB  - The spontaneous polarized Raman spectra of normal and deuterated alcohols (C2-C5)
      have been recorded in the C-H stretching region. In the isotropic Raman spectra,
      a doublet of -CalphaH stretching vibration is found for all alcohols at below
      2900 cm(-1) and above 2950 cm(-1). By comparing the experimental and calculated
      spectra of various deuterated alcohols, the doublets are attributed to the 
      CalphaH stretching vibration of different conformers. For ethanol, the band
      observed at 2970 cm(-1) is assigned as the stretching vibration of -CalphaH in
      the Calpha-O-H plane of the gauche-conformer, while the band at 2895 cm(-1) is
      contributed from both the -CalphaH2 symmetrical stretching vibration of the trans
      conformer and the -CalphaH stretching vibration out of the Calpha-O-H plane of
      the gauche-conformer. The population of gauche-conformer is estimated to be 54%
      in liquid ethanol. For the larger alcohols, the same assignments for the doublet
      are obtained, and the populations of gauche-conformers with plane carbon skeleton
      are found to be slightly larger than that of ethanol, which is consistent with
      results from molecular dynamics simulations.

PMID- 25774683
TI  - 3D-assisted quantitative assessment of orbital volume using an open-source
      software platform in a Taiwanese population.
AB  - Orbital volume evaluation is an important part of pre-operative assessments in
      orbital trauma and congenital deformity patients. The availability of the
      affordable, open-source software, OsiriX, as a tool for preoperative planning
      increased the popularity of radiological assessments by the surgeon. A volume
      calculation method based on 3D volume rendering-assisted region-of-interest
      computation was used to determine the normal orbital volume in Taiwanese patients
      after reorientation to the Frankfurt plane. Method one utilized 3D points for
      intuitive orbital rim outlining. The mean normal orbital volume for left and
      right orbits was 24.3+/-1.51 ml and 24.7+/-1.17 ml in male and 21.0+/-1.21 ml and
      21.1+/-1.30 ml in female subjects. Another method (method two) based on the
      bilateral orbital lateral rim was also used to calculate orbital volume and
      compared with method one. The mean normal orbital volume for left and right
      orbits was 19.0+/-1.68 ml and 19.1+/-1.45 ml in male and 16.0+/-1.01 ml and
      16.1+/-0.92 ml in female subjects. The inter-rater reliability and intra-rater
      measurement accuracy between users for both methods was found to be acceptable
      for orbital volume calculations. 3D-assisted quantification of orbital volume is
      a feasible technique for orbital volume assessment. The normal orbital volume can
      be used as controls in cases of unilateral orbital reconstruction with a mean
      size discrepancy of less than 3.1+/-2.03% in females and 2.7+/-1.32% in males.
      The OsiriX software can be used reliably by the individual surgeon as a
      comprehensive preoperative planning and imaging tool for orbital volume
      measurement and computed tomography reorientation. 

PMID- 25774684
TI  - Resveratrol ameliorates the maturation process of beta-cell-like cells obtained
      from an optimized differentiation protocol of human embryonic stem cells.
AB  - Human embryonic stem cells (hESCs) retain the extraordinary capacity to
      differentiate into different cell types of an adult organism, including
      pancreatic beta-cells. For this particular lineage, although a lot of effort has
      been made in the last ten years to achieve an efficient and reproducible
      differentiation protocol, it was not until recently that this aim was roughly
      accomplished. Besides, several studies evidenced the impact of resveratrol (RSV)
      on insulin secretion, even though the mechanism by which this polyphenol
      potentiates glucose-stimulated insulin secretion (GSIS) is still not clear. The
      aim of this study was to optimize an efficient differentiation protocol that
      mimics in vivo pancreatic organogenesis and to investigate whether RSV may
      improve the final maturation step to obtain functional insulin-secreting cells.
      Our results indicate that treatment of hESCs (HS-181) with activin-A induced
      definitive endoderm differentiation as detected by the expression of SOX17 and
      FOXA2. Addition of retinoic acid (RA), Noggin and Cyclopamine promoted pancreatic
      differentiation as indicated by the expression of the early pancreatic progenitor
      markers ISL1, NGN3 and PDX1. Moreover, during maturation in suspension culture,
      differentiating cells assembled in islet-like clusters, which expressed specific
      endocrine markers such as PDX1, SST, GCG and INS. Similar results were confirmed
      with the human induced Pluripotent Stem Cell (hiPSC) line MSUH-001. Finally,
      differentiation protocols incorporating RSV treatment yielded numerous insulin
      positive cells, induced significantly higher PDX1 expression and were able to
      transiently normalize glycaemia when transplanted in streptozotocin (STZ) induced
      diabetic mice thus promoting its survival. In conclusion, our strategy allows the
      efficient differentiation of hESCs into pancreatic endoderm capable of generating
      beta-cell-like cells and demonstrates that RSV improves the maturation process. 

PMID- 25774685
TI  - Investigation of the curvature induction and membrane localization of the
      influenza virus M2 protein using static and off-magic-angle spinning solid-state
      nuclear magnetic resonance of oriented bicelles.
AB  - A wide variety of membrane proteins induce membrane curvature for function; thus,
      it is important to develop new methods to simultaneously determine membrane
      curvature and protein binding sites in membranes with multiple curvatures. We
      introduce solid-state nuclear magnetic resonance (NMR) methods based on
      magnetically oriented bicelles and off-magic-angle spinning (OMAS) to measure
      membrane curvature and the binding site of proteins in mixed-curvature membranes.
      We demonstrate these methods on the influenza virus M2 protein, which not only
      acts as a proton channel but also mediates virus assembly and membrane scission.
      An M2 peptide encompassing the transmembrane (TM) domain and an amphipathic
      helix, M2(21-61), was studied and compared with the TM peptide (M2TM). Static
      (31)P NMR spectra of magnetically oriented 1,2-dimyristoyl-sn-glycero-3
      phosphocholine (DMPC)/1,2-dihexanoyl-sn-glycero-3-phosphocholine (DHPC) bicelles
      exhibit a temperature-independent isotropic chemical shift in the presence of
      M2(21-61) but not M2TM, indicating that the amphipathic helix confers the ability
      to generate a high-curvature phase. Two-dimensional (2D) (31)P spectra indicate
      that this high-curvature phase is associated with the DHPC bicelle edges,
      suggestive of the structure of budding viruses from the host cell. (31)P- and
      (13)C-detected (1)H relaxation times of the lipids indicate that the majority of
      M2(21-61) is bound to the high-curvature phase. Using OMAS experiments, we
      resolved the (31)P signals of lipids with identical headgroups based on their
      distinct chemical shift anisotropies. On the basis of this resolution, 2D (1)H
      (31)P correlation spectra show that the amide protons in M2(21-61) correlate with
      the DMPC but not DHPC (31)P signal of the bicelle, indicating that a small
      percentage of M2(21-61) partitions into the planar region of the bicelles. These
      results show that the amphipathic helix induces high membrane curvature and
      localizes the protein to this phase, in good agreement with the membrane scission
      function of the protein. These bicelle-based relaxation and OMAS solid-state NMR
      techniques are generally applicable to curvature-inducing membrane proteins such
      as those involved in membrane trafficking, membrane fusion, and cell division. 

PMID- 25774686
TI  - Concentrated protein body product derived from rice endosperm as an oral
      tolerogen for allergen-specific immunotherapy--a new mucosal vaccine formulation
      against Japanese cedar pollen allergy.
AB  - The endoplasmic reticulum-derived type-I protein body (PB-I) from rice endosperm
      cells is an ideal candidate formulation for the oral delivery of bioencapsulated
      peptides as tolerogens for allergen-specific immunotherapy. In the present study,
      PBs containing the deconstructed Japanese cedar pollen allergens Cryptomeria
      japonica 1 (Cry j 1) and Cry j 2 were concentrated by treatment with thermostable
      alpha-amylase at 90 degrees C to remove the starch from milled rice powder, which
      resulted in a 12.5-fold reduction of dry weight compared to the starting
      material. The modified Cry j 1 and Cry j 2 antigens in this concentrated PB
      product were more resistant to enzymatic digestion than those in the milled seed
      powder despite the absence of intact cell wall and starch, and remained stable
      for at least 10 months at room temperature without detectable loss or
      degradation. The high resistance of these allergens could be attributed to
      changes in protein physicochemical properties induced by the high temperature
      concentration process, as suggested by the decreased solubility of the antigens
      and seed proteins in PBs in step-wise-extraction experiments. Confocal microscopy
      showed that the morphology of antigen-containing PB-Is was preserved in the
      concentrated PB product. The concentrated PB product induced specific immune
      tolerance against Cry j 1 and Cry j 2 in mice when orally administered,
      supporting its potential use as a novel oral tolerogen formulation. 

PMID- 25774688
TI  - Aerosol-assisted CVD-grown WO3 nanoneedles decorated with copper oxide
      nanoparticles for the selective and humidity-resilient detection of H2S.
AB  - A gas-sensitive hybrid material consisting of Cu2O nanoparticle-decorated WO3
      nanoneedles is successfully grown for the first time in a single step via aerosol
      assisted chemical vapor deposition. Morphological, structural, and composition
      analyses show that our method is effective for growing single-crystalline, n-type
      WO3 nanoneedles decorated with p-type Cu2O nanoparticles at moderate temperatures
      (i.e., 380  degrees C), with cost effectiveness and short fabrication times,
      directly onto microhot plate transducer arrays with the view of obtaining gas
      sensors. The gas-sensing studies performed show that this hybrid nanomaterial has
      excellent sensitivity and selectivity to hydrogen sulfide (7-fold increase in
      response compared with that of pristine WO3 nanoneedles) and a low detection
      limit (below 300 ppb of H2S), together with unprecedented fast response times (2
      s) and high immunity to changes in the background humidity. These superior
      properties arise because of the multiple p-n heterojunctions created at the
      nanoscale in our hybrid nanomaterial. 

PMID- 25774687
TI  - The identification of specific methylation patterns across different cancers.
AB  - Abnormal DNA methylation is known as playing an important role in the
      tumorgenesis. It is helpful for distinguishing the specificity of diagnosis and
      therapeutic targets for cancers based on characteristics of DNA methylation
      patterns across cancers. High throughput DNA methylation analysis provides the
      possibility to comprehensively filter the epigenetics diversity across various
      cancers. We integrated whole-genome methylation data detected in 798 samples from
      seven cancers. The hierarchical clustering revealed the existence of cancer
      specific methylation pattern. Then we identified 331 differentially methylated
      genes across these cancers, most of which (266) were specifically differential
      methylation in unique cancer. A DNA methylation correlation network (DMCN) was
      built based on the methylation correlation between these genes. It was shown the
      hubs in the DMCN were inclined to cancer-specific genes in seven cancers. Further
      survival analysis using the part of genes in the DMCN revealed high-risk group
      and low-risk group were distinguished by seven biomarkers (PCDHB15, WBSCR17,
      IGF1, GYPC, CYGB, ACTG2, and PRRT1) in breast cancer and eight biomarkers
      (ZBTB32, OR51B4, CCL8, TMEFF2, SALL3, GPSM1, MAGEA8, and SALL1) in colon cancer,
      respectively. At last, a protein-protein interaction network was introduced to
      verify the biological function of differentially methylated genes. It was shown
      that MAP3K14, PTN, ACVR1 and HCK sharing different DNA methylation and gene
      expression across cancers were relatively high degree distribution in PPI
      network. The study suggested that not only the identified cancer-specific genes
      provided reference for individual treatment but also the relationship across
      cancers could be explained by differential DNA methylation. 

PMID- 25774689
TI  - Functions of multivector variables.
AB  - As is well known, the common elementary functions defined over the real numbers
      can be generalized to act not only over the complex number field but also over
      the skew (non-commuting) field of the quaternions. In this paper, we detail a
      number of elementary functions extended to act over the skew field of Clifford
      multivectors, in both two and three dimensions. Complex numbers, quaternions and
      Cartesian vectors can be described by the various components within a Clifford
      multivector and from our results we are able to demonstrate new inter
      relationships between these algebraic systems. One key relationship that we
      discover is that a complex number raised to a vector power produces a quaternion
      thus combining these systems within a single equation. We also find a single
      formula that produces the square root, amplitude and inverse of a multivector
      over one, two and three dimensions. Finally, comparing the functions over
      different dimension we observe that Cl(R(3)) provides a particularly versatile
      algebraic framework.

PMID- 25774690
TI  - Correction: Evaluating the cost-effectiveness of lifestyle modification versus
      metformin therapy for the prevention of diabetes in Singapore.

PMID- 25774692
TI  - Correction: Quantitative reconstruction of weaning ages in archaeological human
      populations using bone collagen nitrogen isotope ratios and approximate bayesian
      computation.

PMID- 25774691
TI  - Anthocyanins attenuate alcohol-induced hepatic injury by inhibiting pro
      inflammation signalling.
AB  - We assessed phytochemical components of anthocyanins from purple sweet potato
      (PSP) and purple potato (PP) with UPLC-MS/MS, and investigated their inhibitory
      effect on inflammatory response in alcoholic liver disease (ALD). Results showed
      that serum AST and ALT levels in PP anthocyanins (PPAs) and PSP anthocyanins
      (PSPAs) treatments were lower than those of alcohol-treated group. PPAs and PSPAs
      could inhibit mRNA expressions of inflammatory factors (TNF-alpha, VCAM-1, IFN
      gamma and CXCL-1). The mRNA levels of NF-kappaB, STAT, and TLR in PPAs and PSPAs
      treatment groups were lower than in alcohol treatment group. Our results indicate
      that PP and PSP are good source of anti-inflammatory anthocyanins to prevent ALD.

PMID- 25774693
TI  - Recall of briefly presented chess positions and its relation to chess skill.
AB  - Individual differences in memory performance in a domain of expertise have
      traditionally been accounted for by previously acquired chunks of knowledge and
      patterns. These accounts have been examined experimentally mainly in chess. The
      role of chunks (clusters of chess pieces recalled in rapid succession during
      recall of chess positions) and their relations to chess skill are, however, under
      debate. By introducing an independent chunk-identification technique, namely
      repeated-recall technique, this study identified individual chunks for particular
      chess players. The study not only tested chess players with increasing chess
      expertise, but also tested non-chess players who should not have previously
      acquired any chess related chunks in memory. For recall of game positions
      significant differences between players and non-players were found in virtually
      all the characteristics of chunks recalled. Size of the largest chunks also
      correlates with chess skill within the group of rated chess players. Further
      research will help us understand how these memory encodings can explain large
      differences in chess skill. 

PMID- 25774695
TI  - Direct visualization of spatiotemporal structure of self-assembled colloidal
      particles in electrohydrodynamic flow of a nematic liquid crystal.
AB  - Characterization of spatiotemporal dynamics is of vital importance to soft matter
      systems far from equilibrium. Using a confocal laser scanning microscopy, we
      directly reveal three-dimensional motion of surface-modified particles in the
      electrohydrodynamic convection of a nematic liquid crystal. Particularly,
      visualizing a caterpillar-like motion of a self-assembled colloidal chain
      demonstrates the mechanism of the persistent transport enabled by the elastic,
      electric, and hydrodynamic contributions. We also precisely show how the
      particles' trajectory is spatially modified by simply changing the surface
      boundary condition. 

PMID- 25774697
TI  - Chiral thiahelicene-based alkyl phosphine-borane complexes: synthesis, X-ray
      characterization, and theoretical and experimental investigations of optical
      properties.
AB  - Chiral helical-based phosphanes are challenging and promising ligands, with a
      great potential for the generation of both organic and organometallic catalysts.
      We report here the preparation of novel chiral thiahelicene-based alkyl
      phosphanes, isolated and characterized as air-stable borane adducts, and the
      investigation of their experimental and theoretical (chir)optical properties. X
      ray characterization of a mono- and a disubstituted derivative as a racemic
      mixture has been performed, which confirms the influence of the number and nature
      of substituents on the flexibility of the helix. In addition, the absolute
      configuration inferred from CD spectra of the two enantiomers of a diborane
      complex has been established from X-ray analysis. State-of-the-art quantum
      chemical calculations of vibrationally resolved spectra allow, for the first
      time, for an unambiguous assignment of the experimentally observed peaks in
      linear absorption and circular dichroism spectra to excited electronic states of
      this class of thiahelicene phosphorus derivatives. 

PMID- 25774694
TI  - Human T-cell leukemia virus type 1 (HTLV-1) tax requires CADM1/TSLC1 for
      inactivation of the NF-kappaB inhibitor A20 and constitutive NF-kappaB signaling.
AB  - Persistent activation of NF-kappaB by the Human T-cell leukemia virus type 1
      (HTLV-1) oncoprotein, Tax, is vital for the development and pathogenesis of adult
      T-cell leukemia (ATL) and HTLV-1-associated myelopathy/tropical spastic
      paraparesis (HAM/TSP). K63-linked polyubiquitinated Tax activates the IKK complex
      in the plasma membrane-associated lipid raft microdomain. Tax also interacts with
      TAX1BP1 to inactivate the NF-kappaB negative regulatory ubiquitin-editing A20
      enzyme complex. However, the molecular mechanisms of Tax-mediated IKK activation
      and A20 protein complex inactivation are poorly understood. Here, we demonstrated
      that membrane associated CADM1 (Cell adhesion molecule1) recruits Ubc13 to Tax,
      causing K63-linked polyubiquitination of Tax, and IKK complex activation in the
      membrane lipid raft. The c-terminal cytoplasmic tail containing PDZ binding motif
      of CADM1 is critical for Tax to maintain persistent NF-kappaB activation.
      Finally, Tax failed to inactivate the NF-kappaB negative regulator ubiquitin
      editing enzyme A20 complex, and activate the IKK complex in the lipid raft in
      absence of CADM1. Our results thus indicate that CADM1 functions as a critical
      scaffold molecule for Tax and Ubc13 to form a cellular complex with NEMO, TAX1BP1
      and NRP, to activate the IKK complex in the plasma membrane-associated lipid
      rafts, to inactivate NF-kappaB negative regulators, and maintain persistent NF
      kappaB activation in HTLV-1 infected cells. 

PMID- 25774698
TI  - Mechanisms of patient health behavior change in a randomized controlled trial of
      a spouse-assisted intervention.
AB  - Spouse-assisted interventions can improve health behaviors, but mechanisms of
      action are unknown. This study evaluated mediators of dietary and physical
      activity outcomes during a spouse-assisted intervention to improve low-density
      lipoprotein cholesterol. This is a secondary analysis of data from a randomized
      controlled trial comparing usual care (n = 128) to a spouse-assisted lifestyle
      change intervention (n = 127) comprising nine monthly goal setting telephone
      calls to participants and support planning calls to spouses over 11 months.
      Structural equation modeling was used to examine if the intervention influenced
      the putative mediators of participant self-efficacy and perceived spousal support
      at 6 months (i.e. action test); if changes in putative mediators at 6 months were
      associated with changes in diet and physical activity outcomes at 11 months (i.e.
      conceptual test); and if treatment condition effects on outcomes at 11 months
      were mediated by its effects on the 6-month putative mediators (i.e. indirect
      effects test). Participants were 94.9% male, 64.9% white and were 61.3 years old
      on average. The action test showed that the intervention increased dietary self
      efficacy (p < .001) and perceived spousal support for diet (p < .001) and
      physical activity (p < .01) at 6 months. The conceptual test showed that
      increases in participant physical activity self-efficacy at 6 months were
      associated with increases in physical activity frequency (p = .01) and duration
      (p = .04) at 11 months; other putative mediators were not associated with changes
      in outcomes at 11 months. The indirect effects tests did not support a mediating
      role for self-efficacy or perceived spousal support. Intervention-induced changes
      in spousal support and dietary self-efficacy did not translate into behavior
      change. Other mechanisms may be driving behavior change.

PMID- 25774696
TI  - Mesenchymal stromal cell secretome up-regulates 47 kDa CXCR4 expression, and
      induce invasiveness in neuroblastoma cell lines.
AB  - Neuroblastoma accounts for 15% of childhood cancer deaths and presents with
      metastatic disease of the bone and the bone marrow at diagnosis in 70% of the
      cases. Previous studies have shown that the Mesenchymal Stromal Cell (MSC)
      secretome, triggers metastases in several cancer types such as breast and
      prostate cancer, but the specific role of the MSC factors in neuroblastoma
      metastasis is unclear. To better understand the effect of MSC secretome on
      chemokine receptors in neuroblastoma, and its role in metastasis, we studied a
      panel of 20 neuroblastoma cell lines, and compared their invasive potential
      towards MSC-conditioned-RPMI (mRPMI) and their cytokine receptor expression
      profiles. Western blot analysis revealed the expression of multiple CXCR4
      isoforms in neuroblastoma cells. Among the five major isoforms, the expression of
      the 47 kDa isoform showed significant correlation with high invasiveness.
      Pretreatment with mRPMI up-regulated the expression of the 47 kDa CXCR4 isoform
      and also increased MMP-9 secretion, expression of integrin alpha3 and integrin
      beta1, and the invasive potential of the cell; while blocking CXCR4 either with
      AMD 3100, a CXCR4 antagonist, or with an anti-47 kDa CXCR4 neutralizing antibody
      decreased the secretion of MMP-9, the expression of integrin alpha3 and integrin
      beta1, and the invasive potential of the cell. Pretreatment with mRPMI also
      protected the 47 kDa CXCR4 isoform from ubiquitination and subsequent
      degradation. Our data suggest a modulatory role of the MSC secretome on the
      expression of the 47 kDa CXCR4 isoform and invasion potential of the
      neuroblastoma cells to the bone marrow. 

PMID- 25774699
TI  - Alcohol and Femininity in Sweden c. 1830-1922: An Investigation of the Emergence
      of Separate Drinking Standards for Men and Women.
AB  - This paper discusses changing views about gender and drinking in Sweden c. 1830
      1922. The author posits that the emergence of bourgeois morals in the 19th
      century were associated with a decline in the tolerance for female alcohol
      consumption, and also shows how the values, norms, and activities of the
      temperance movement interconnected with religion and notions of purity. Yet, in
      spite of hardening attitudes against women's drinking, alcohol remained integral
      in Swedish upper-class women's lives. The results are based on a qualitative
      study of Swedish women's diaries. The study was financed by the Swedish Research
      Council, 2009-2012. Study limitations are also noted. 

PMID- 25774700
TI  - Osteometric sex determination using proximal foot phalanges from a documented
      human skeletal collection.
AB  - Diagnosing sex is vital for developing biological profiles from human skeletal
      remains. For that purpose, osteometric evaluation of bone size has proven to be
      usually effective. The present study investigates the degree of sexual dimorphism
      in proximal foot phalanges from a documented human skeletal collection, known as
      the Athens collection. Furthermore, it utilizes the data for the development of
      sex-discriminant formulas in Greek population. The material used consists of 749
      proximal foot phalanges (left and right), which belong to 174 adult individuals
      (91 males and 83 females) that lived during the 20(th) century. The degree of
      sexual dimorphism reached as high as 16.76 %, with the left side demonstrating
      higher sexual dimorphism. The 1(st) proximal foot phalanges are proven to be the
      most sexually dimorphic among the bones of the sample. The minimum sexual
      dimorphism observed was in the maximum lengths of phalanges, whereas the most
      sexually dimorphic measurement was the medio-lateral width at midshaft. The
      discriminant functions developed provide classification accuracies that ranged
      between 77.1 % and 90.9 % for left and between 72.2 % and 86.6 % for right
      proximal foot phalanges. The results of this study suggest that proximal foot
      phalanges are useful for sex determination in Greek population.

PMID- 25774701
TI  - A reverse-action clip applier for aneurysm surgery.
AB  - BACKGROUND: Clipping is an important technique for cerebral aneurysm surgery.
      Although clip mechanisms and features have been refined, little attention has
      been paid to clip appliers. Clip closure is traditionally achieved by opening the
      grip of the clip applier. We reconsidered this motion and identified an important
      drawback, namely that the standard applier holding power decreased at the moment
      of clip release, which could lead to unstable clip application. OBJECTIVE: To
      develop a forceps to address this clip applier design flaw. METHODS: The new clip
      applier has a non--cross-type fulcrum that is closed at the time of clip release,
      with an action similar to that of a bipolar forceps or scissors. Thus, a surgeon
      can steadily apply the clip from various angles. RESULTS: We successfully used
      our clip applier to treat 103 aneurysms. Although training was required to ensure
      smooth applier use, no difficulties associated with applier use were noted.
      CONCLUSION: This clip applier can improve clipping surgery safety because it
      offers additional stability during clip release.

PMID- 25774702
TI  - Simpson Grade I-III Resection of Spinal Atypical (World Health Organization Grade
      II) Meningiomas is Associated With Symptom Resolution and Low Recurrence.
AB  - BACKGROUND: Because of their rarity, outcomes regarding spinal atypical
      meningiomas (AMs) remain unclear. OBJECTIVE: To describe the recurrence rate and
      postoperative outcomes after resection of spinal AMs, and to discuss an
      appropriate resection strategy and adjuvant therapy for spinal AMs. METHODS: Data
      from all patients who presented with spinal AMs to 2 tertiary referral centers
      between 1998 and 2013 were obtained by chart review. RESULTS: From 102 patients
      with spinal meningioma, 20 AM tumors (7 cervical, 11 thoracic, 2 thoracolumbar)
      were identified in 18 patients (median age, 50 years [range, 19-75] at time of
      resection; 11% male; median follow-up, 32 months [range, 1-179] after resection).
      Before resection, patients had sensory deficits (70%), pain (70%), weakness
      (60%), ataxia (50%), spasticity (65%), and incontinence (35%). One tumor
      presented asymptomatically. Simpson grade I, II, III, and IV resection were
      achieved in 3 (15%), 13 (65%), 2 (10%), and 2 (10%) tumors, respectively. One
      patient that underwent Simpson grade III resection received adjuvant radiation
      therapy. After Simpson grade I-III or gross total resection, no tumors recurred
      (0%; confidence interval, 0%-17.6%). After Simpson grade IV resection, 1 tumor
      recurred (50%; confidence interval, 1.3%-98.7%). With the exception of 1 patient
      who had bilateral paraplegia perioperatively, all other patients experienced
      improvement of preoperative symptoms after surgery (median time, 3.6 months
      [range, 1-13] after resection). CONCLUSION: Despite published cases suggesting an
      aggressive clinical course for spinal AMs, this series of spinal AMs reports that
      gross total resection without adjuvant radiation therapy resulted in symptom
      resolution and low recurrence.

PMID- 25774703
TI  - Validation of a High-Performance Liquid Chromatography-Tandem Mass Spectrometry
      Method for the Determination of Perhexiline and Cis-Hydroxy-Perhexiline Plasma
      Concentrations.
AB  - BACKGROUND: The polymorphic nature of cytochrome P450 2D6 has made therapeutic
      drug monitoring of the anti-anginal agent perhexiline a compulsory step in
      reducing adverse events associated with plasma concentrations above the
      therapeutic range (0.15-0.60 mg/L). The aim of this study was to develop a high
      performance liquid chromatography-mass spectrometry/mass spectrometry method for
      the determination of plasma perhexiline concentrations and its major metabolite
      cis-hydroxy-perhexiline to reduce sample extraction procedures and improve sample
      turnaround times. METHODS: The method was validated by determining the precision
      and accuracy of calibrators and quality control material, comparing quality
      assurance program samples and patient samples measured by a previously reported
      liquid-liquid extraction fluorescence (FL) detection high-performance liquid
      chromatography method and performing matrix effects investigations. RESULTS:
      Replicates of calibrators at concentrations of 3.00 and 0.05 mg/L demonstrated
      imprecision of <10.8% and inaccuracy of <8.2% for perhexiline and <10.1% and
      <4.5% for cis-hydroxy-perhexiline, respectively. All samples measured by the 2
      methods (n = 102) demonstrated Deming regression of perhexiline = 1.20 FL + 0.00
      (Sy.x = 0.08, 1/slope = 0.67); cis-hydroxy-perhexiline = 1.48 FL - 0.20 (Sy.x =
      0.40, 1/slope = 0.67). CONCLUSIONS: The assay performance was deemed acceptable
      and integrated into the routine therapeutic drug monitoring program of the
      department.

PMID- 25774704
TI  - Excel-Based Tool for Pharmacokinetically Guided Dose Adjustment of Paclitaxel.
AB  - BACKGROUND: Neutropenia is a frequent and severe adverse event in patients
      receiving paclitaxel chemotherapy. The time above a paclitaxel threshold
      concentration of 0.05 MUmol/L (Tc > 0.05 MUmol/L) is a strong predictor for
      paclitaxel-associated neutropenia and has been proposed as a target
      pharmacokinetic (PK) parameter for paclitaxel therapeutic drug monitoring and
      dose adaptation. Up to now, individual Tc > 0.05 MUmol/L values are estimated
      based on a published PK model of paclitaxel by using the software NONMEM. Because
      many clinicians are not familiar with the use of NONMEM, an Excel-based dosing
      tool was developed to allow calculation of paclitaxel Tc > 0.05 MUmol/L and give
      clinicians an easy-to-use tool. METHODS: Population PK parameters of paclitaxel
      were taken from a published PK model. An Alglib VBA code was implemented in Excel
      2007 to compute differential equations for the paclitaxel PK model. Maximum a
      posteriori Bayesian estimates of the PK parameters were determined with the Excel
      Solver using individual drug concentrations. Concentrations from 250 patients
      were simulated receiving 1 cycle of paclitaxel chemotherapy. Predictions of
      paclitaxel Tc > 0.05 MUmol/L as calculated by the Excel tool were compared with
      NONMEM, whereby maximum a posteriori Bayesian estimates were obtained using the
      POSTHOC function. RESULTS: There was a good concordance and comparable predictive
      performance between Excel and NONMEM regarding predicted paclitaxel plasma
      concentrations and Tc > 0.05 MUmol/L values. Tc > 0.05 MUmol/L had a maximum bias
      of 3% and an error on precision of <12%. The median relative deviation of the
      estimated Tc > 0.05 MUmol/L values between both programs was 1%. CONCLUSIONS: The
      Excel-based tool can estimate the time above a paclitaxel threshold concentration
      of 0.05 MUmol/L with acceptable accuracy and precision. The presented Excel tool
      allows reliable calculation of paclitaxel Tc > 0.05 MUmol/L and thus allows
      target concentration intervention to improve the benefit-risk ratio of the drug.
      The easy use facilitates therapeutic drug monitoring in clinical routine.

PMID- 25774706
TI  - Color filtering localization for three-dimensional underwater acoustic sensor
      networks.
AB  - Accurate localization of mobile nodes has been an important and fundamental
      problem in underwater acoustic sensor networks (UASNs). The detection information
      returned from a mobile node is meaningful only if its location is known. In this
      paper, we propose two localization algorithms based on color filtering technology
      called PCFL and ACFL. PCFL and ACFL aim at collaboratively accomplishing accurate
      localization of underwater mobile nodes with minimum energy expenditure. They
      both adopt the overlapping signal region of task anchors which can communicate
      with the mobile node directly as the current sampling area. PCFL employs the
      projected distances between each of the task projections and the mobile node,
      while ACFL adopts the direct distance between each of the task anchors and the
      mobile node. The proportion factor of distance is also proposed to weight the RGB
      values. By comparing the nearness degrees of the RGB sequences between the
      samples and the mobile node, samples can be filtered out. The normalized nearness
      degrees are considered as the weighted standards to calculate the coordinates of
      the mobile nodes. The simulation results show that the proposed methods have
      excellent localization performance and can localize the mobile node in a timely
      way. The average localization error of PCFL is decreased by about 30.4% compared
      to the AFLA method. 

PMID- 25774705
TI  - Policaptil Gel Retard significantly reduces body mass index and hyperinsulinism
      and may decrease the risk of type 2 diabetes mellitus (T2DM) in obese children
      and adolescents with family history of obesity and T2DM.
AB  - BACKGROUND: Treatments for childhood obesity are critically needed because of the
      risk of developing co-morbidities, although the interventions are frequently time
      consuming, frustrating, difficult, and expensive. PATIENTS AND METHODS: We
      conducted a longitudinal, randomised, clinical study, based on a per protocol
      analysis, on 133 obese children and adolescents (n = 69 males and 64 females;
      median age, 11.3 years) with family history of obesity and type 2 diabetes
      mellitus (T2DM). The patients were divided into three arms: Arm A (n = 53
      patients), Arm B (n = 45 patients), and Arm C (n = 35 patients) patients were
      treated with a low-glycaemic-index (LGI) diet and Policaptil Gel Retard, only a
      LGI diet, or only an energy-restricted diet (ERD), respectively. The homeostasis
      model assessment of insulin resistance (HOMA-IR) and the Matsuda, insulinogenic
      and disposition indexes were calculated at T0 and after 1 year (T1). RESULTS: At
      T1, the BMI-SD scores were significantly reduced from 2.32 to 1.80 (p < 0.0001)
      in Arm A and from 2.23 to 1.99 (p < 0.05) in Arm B. Acanthosis nigricans was
      significantly reduced in Arm A (13.2% to 5.6%; p < 0.05), and glycosylated
      haemoglobin levels were significantly reduced in Arms A (p < 0.005). The
      percentage of glucose-metabolism abnormalities was reduced, although not
      significantly. However, the HOMA-IR index was significantly reduced in Arms A (p
      < 0.0001) and B (p < 0.05), with Arm A showing a significant reduction in the
      insulinogenic index (p < 0.05). Finally, the disposition index was significantly
      improved in Arms A (p < 0.0001) and B (p < 0.05). CONCLUSIONS: A LGI diet,
      particularly associated with the use of Policaptil Gel Retard, may reduce weight
      gain and ameliorate the metabolic syndrome and insulin-resistance parameters in
      obese children and adolescents with family history of obesity and T2DM.

PMID- 25774707
TI  - Omnidirectional underwater camera design and calibration.
AB  - This paper presents the development of an underwater omnidirectional multi-camera
      system (OMS) based on a commercially available six-camera system, originally
      designed for land applications. A full calibration method is presented for the
      estimation of both the intrinsic and extrinsic parameters, which is able to cope
      with wide-angle lenses and non-overlapping cameras simultaneously. This method is
      valid for any OMS in both land or water applications. For underwater use, a
      customized housing is required, which often leads to strong image distortion due
      to refraction among the different media. This phenomena makes the basic pinhole
      camera model invalid for underwater cameras, especially when using wide-angle
      lenses, and requires the explicit modeling of the individual optical rays. To
      address this problem, a ray tracing approach has been adopted to create a field
      of-view (FOV) simulator for underwater cameras. The simulator allows for the
      testing of different housing geometries and optics for the cameras to ensure a
      complete hemisphere coverage in underwater operation. This paper describes the
      design and testing of a compact custom housing for a commercial off-the-shelf OMS
      camera (Ladybug 3) and presents the first results of its use. A proposed three
      stage calibration process allows for the estimation of all of the relevant camera
      parameters. Experimental results are presented, which illustrate the performance
      of the calibration method and validate the approach. 

PMID- 25774708
TI  - Data fault detection in medical sensor networks.
AB  - Medical body sensors can be implanted or attached to the human body to monitor
      the physiological parameters of patients all the time. Inaccurate data due to
      sensor faults or incorrect placement on the body will seriously influence
      clinicians' diagnosis, therefore detecting sensor data faults has been widely
      researched in recent years. Most of the typical approaches to sensor fault
      detection in the medical area ignore the fact that the physiological indexes of
      patients aren't changing synchronously at the same time, and fault values mixed
      with abnormal physiological data due to illness make it difficult to determine
      true faults. Based on these facts, we propose a Data Fault Detection mechanism in
      Medical sensor networks (DFD-M). Its mechanism includes: (1) use of a dynamic
      local outlier factor (D-LOF) algorithm to identify outlying sensed data vectors;
      (2) use of a linear regression model based on trapezoidal fuzzy numbers to
      predict which readings in the outlying data vector are suspected to be faulty;
      (3) the proposal of a novel judgment criterion of fault state according to the
      prediction values. The simulation results demonstrate the efficiency and
      superiority of DFD-M. 

PMID- 25774710
TI  - In-network processing of an iceberg join query in wireless sensor networks based
      on 2-way fragment semijoins.
AB  - We investigate the in-network processing of an iceberg join query in wireless
      sensor networks (WSNs). An iceberg join is a special type of join where only
      those joined tuples whose cardinality exceeds a certain threshold (called iceberg
      threshold) are qualified for the result. Processing such a join involves the
      value matching for the join predicate as well as the checking of the cardinality
      constraint for the iceberg threshold. In the previous scheme, the value matching
      is carried out as the main task for filtering non-joinable tuples while the
      iceberg threshold is treated as an additional constraint. We take an alternative
      approach, meeting the cardinality constraint first and matching values next. In
      this approach, with a logical fragmentation of the join operand relations on the
      aggregate counts of the joining attribute values, the optimal sequence of 2-way
      fragment semijoins is generated, where each fragment semijoin employs a Bloom
      filter as a synopsis of the joining attribute values. This sequence filters non
      joinable tuples in an energy-efficient way in WSNs. Through implementation and a
      set of detailed experiments, we show that our alternative approach considerably
      outperforms the previous one. 

PMID- 25774709
TI  - Low-cost photolithographic fabrication of nanowires and microfilters for advanced
      bioassay devices.
AB  - Integrated microfluidic devices with nanosized array electrodes and
      microfiltration capabilities can greatly increase sensitivity and enhance
      automation in immunoassay devices. In this contribution, we utilize the edge
      patterning method of thin aluminum (Al) films in order to form nano- to micron
      sized gaps. Evaporation of high work-function metals (i.e., Au, Ag, etc.) on
      these gaps, followed by Al lift-off, enables the formation of electrical uniform
      nanowires from low-cost, plastic-based, photomasks. By replacing Al with chromium
      (Cr), the formation of high resolution, custom-made photomasks that are ideal for
      low-cost fabrication of a plurality of array devices were realized. To
      demonstrate the feasibility of such Cr photomasks, SU-8 micro-pillar masters were
      formed and replicated into PDMS to produce micron-sized filters with 3-4 um gaps
      and an aspect ratio of 3. These microfilters were capable of retaining 6 um beads
      within a localized site, while allowing solvent flow. The combination of nanowire
      arrays and micro-pillar filtration opens new perspectives for rapid R&D screening
      of various microfluidic-based immunoassay geometries, where analyte pre
      concentration and highly sensitive, electrochemical detection can be readily co
      localized. 

PMID- 25774711
TI  - Translational diffusion of hydration water correlates with functional motions in
      folded and intrinsically disordered proteins.
AB  - Hydration water is the natural matrix of biological macromolecules and is
      essential for their activity in cells. The coupling between water and protein
      dynamics has been intensively studied, yet it remains controversial. Here we
      combine protein perdeuteration, neutron scattering and molecular dynamics
      simulations to explore the nature of hydration water motions at temperatures
      between 200 and 300 K, across the so-called protein dynamical transition, in the
      intrinsically disordered human protein tau and the globular maltose binding
      protein. Quasi-elastic broadening is fitted with a model of translating, rotating
      and immobile water molecules. In both experiment and simulation, the
      translational component markedly increases at the protein dynamical transition
      (around 240 K), regardless of whether the protein is intrinsically disordered or
      folded. Thus, we generalize the notion that the translational diffusion of water
      molecules on a protein surface promotes the large-amplitude motions of proteins
      that are required for their biological activity. 

PMID- 25774712
TI  - Incidence of nodal metastasis and isolated aortic metastases in patients with
      surgically staged endometrioid endometrial cancer.
AB  - OBJECTIVES: To describe the incidence of lymph node metastasis in patients with
      surgically staged endometrioid-type endometrial cancer in Donostia University
      Hospital and evaluate the presence of isolated aortic metastasis. METHODS: Using
      a prospectively maintained database, we recorded all cases of endometrioid
      endometrial cancer that underwent lymph node dissection and determined the rate
      and location (pelvic or para-aortic) of lymph node metastasis. RESULTS: A total
      of 212 patients with endometrioid type endometrial cancer were surgically treated
      at our institution from May 2008 to June 2013. Ninety underwent pelvic and para
      aortic lymphadenectomy. Thirteen had positive nodes upon pathological
      examination. Six (6.6%) of 90 patients had positive para-aortic nodes with
      negative pelvic nodes. CONCLUSIONS: In our series, the incidence of isolated
      aortic nodal metastasis is high compared with other published reports. Performing
      aortic lymphadenectomy only in case of positive pelvic nodes would have
      underdiagnosed 6 (46%) of 13 stage IIIC cancers.

PMID- 25774713
TI  - High-throughput fluorescence correlation spectroscopy enables analysis of
      proteome dynamics in living cells.
AB  - To understand the function of cellular protein networks, spatial and temporal
      context is essential. Fluorescence correlation spectroscopy (FCS) is a single
      molecule method to study the abundance, mobility and interactions of fluorescence
      labeled biomolecules in living cells. However, manual acquisition and analysis
      procedures have restricted live-cell FCS to short-term experiments of a few
      proteins. Here, we present high-throughput (HT)-FCS, which automates screening
      and time-lapse acquisition of FCS data at specific subcellular locations and
      subsequent data analysis. We demonstrate its utility by studying the dynamics of
      53 nuclear proteins. We made 60,000 measurements in 10,000 living human cells, to
      obtain biophysical parameters that allowed us to classify proteins according to
      their chromatin binding and complex formation. We also analyzed the cell-cycle
      dependent dynamics of the mitotic kinase complex Aurora B/INCENP and showed how a
      rise in Aurora concentration triggers two-step complex formation. We expect that
      throughput and robustness will make HT-FCS a broadly applicable technology for
      characterizing protein network dynamics in cells. 

PMID- 25774714
TI  - Identification of human T-cell receptors with optimal affinity to cancer antigens
      using antigen-negative humanized mice.
AB  - Identifying T-cell receptors (TCRs) that bind tumor-associated antigens (TAAs)
      with optimal affinity is a key bottleneck in the development of adoptive T-cell
      therapy of cancer. TAAs are unmutated self proteins, and T cells bearing high
      affinity TCRs specific for such antigens are commonly deleted in the thymus. To
      identify optimal-affinity TCRs, we generated antigen-negative humanized mice with
      a diverse human TCR repertoire restricted to the human leukocyte antigen (HLA)
      A*02:01 (ref. 3). These mice were immunized with human TAAs, for which they are
      not tolerant, allowing induction of CD8+ T cells with optimal-affinity TCRs. We
      isolate TCRs specific for the cancer/testis (CT) antigen MAGE-A1 (ref. 4) and
      show that two of them have an anti-tumor effect in vivo. By comparison, human
      derived TCRs have lower affinity and do not mediate substantial therapeutic
      effects. We also identify optimal-affinity TCRs specific for the CT antigen NY
      ESO. Our humanized mouse model provides a useful tool for the generation of
      optimal-affinity TCRs for T-cell therapy.

PMID- 25774715
TI  - The transcription factor IRF1 and guanylate-binding proteins target activation of
      the AIM2 inflammasome by Francisella infection.
AB  - Inflammasomes are critical for mounting host defense against pathogens. The
      molecular mechanisms that control activation of the AIM2 inflammasome in response
      to different cytosolic pathogens remain unclear. Here we found that the
      transcription factor IRF1 was required for activation of the AIM2 inflammasome
      during infection with the Francisella tularensis subspecies novicida (F.
      novicida), whereas engagement of the AIM2 inflammasome by mouse cytomegalovirus
      (MCMV) or transfected double-stranded DNA did not require IRF1. Infection of F.
      novicida detected by the DNA sensor cGAS and its adaptor STING induced type I
      interferon-dependent expression of IRF1, which drove the expression of guanylate
      binding proteins (GBPs); this led to intracellular killing of bacteria and DNA
      release. Our results reveal a specific requirement for IRF1 and GBPs in the
      liberation of DNA for sensing by AIM2 depending on the pathogen encountered by
      the cell. 

PMID- 25774717
TI  - Photochemical behavior of 2-azidopurine tri-O-acetylribonucleoside in aqueous
      solution: unprecedented transformation into 1-(5'-O-acetyl-beta-D-ribofuranosyl)
      5-[(2-oxo-1,3,5-oxadiazocan-4-ylidene)amino]-1H-imidazole-4-carbaldehyde.
AB  - The photochemical behavior of 2-azidopurine 2',3',5'-tri-O-acetylribonucleoside
      has been investigated in aqueous solution under aerobic and anaerobic conditions.
      The two major processes under anaerobic irradiation of 2-azidopurine 2',3',5'-tri
      O-acetylribonucleoside involve unprecedented transformation into 1-(5'-O-acetyl
      beta-D-ribofuranosyl)-5-[(2-oxo-1,3,5-oxadiazocan-4-ylidene)amino]-1H-imidazole-4
      carbaldehyde and photoreduction to respective 2-aminopurine derivative, whereas
      under aerobic conditions these two processes occur to a much lesser extent and
      photooxidation to respective 2-nitropurine derivative dominates. The structures
      of photoproducts formed were confirmed by NMR and high-resolution electrospray
      ionization mass spectral data.

PMID- 25774716
TI  - Guanylate-binding proteins promote activation of the AIM2 inflammasome during
      infection with Francisella novicida.
AB  - The AIM2 inflammasome detects double-stranded DNA in the cytosol and induces
      caspase-1-dependent pyroptosis as well as release of the inflammatory cytokines
      interleukin 1beta (IL-1beta) and IL-18. AIM2 is critical for host defense against
      DNA viruses and bacteria that replicate in the cytosol, such as Francisella
      tularensis subspecies novicida (F. novicida). The activation of AIM2 by F.
      novicida requires bacteriolysis, yet whether this process is accidental or is a
      host-driven immunological mechanism has remained unclear. By screening nearly 500
      interferon-stimulated genes (ISGs) through the use of small interfering RNA
      (siRNA), we identified guanylate-binding proteins GBP2 and GBP5 as key activators
      of AIM2 during infection with F. novicida. We confirmed their prominent role in
      vitro and in a mouse model of tularemia. Mechanistically, these two GBPs targeted
      cytosolic F. novicida and promoted bacteriolysis. Thus, in addition to their role
      in host defense against vacuolar pathogens, GBPs also facilitate the presentation
      of ligands by directly attacking cytosolic bacteria. 

PMID- 25774718
TI  - Thrombin or Ca(++)-ionophore-mediated fall in endothelial ATP levels independent
      of poly(ADP-Ribose) polymerase activity and NAD levels--comparison with the
      effects of hydrogen peroxide.
AB  - To test the hypothesis that a fall in cellular ATP following stimulation of
      endothelial cells with thrombin is secondary to a decrease in NAD levels caused
      by poly(ADP-Ribose)polymerase (PARP), we measured the levels of NAD and ATP in
      endothelial cells after treatment with thrombin, the Ca(++)-ionophore A23187, or
      hydrogen peroxide (H2O2), and compared the effects of inhibitors of PARP, NAD
      synthesis, and ADP-ribose breakdown on these responses. Neither thrombin nor
      A23187 caused a reduction in endothelial NAD levels and A23187 affected ATP
      levels independently of NAD levels or PARP activity. H2O2 induced lowering of NAD
      caused modest lowering of ATP but marked additional ATP-lowering, independent of
      PARP and NAD, was also demonstrated. We conclude that in endothelial cells ATP
      levels are largely independent of NAD and PARP, which do not play a role in
      thrombin or Ca(++)-ionophore-mediated lowering of ATP. H2O2 caused ATP lowering
      through a similar mechanism as thrombin and A23187 but, additionally, caused a
      further ATP lowering through its intense stimulation of PARP and marked lowering
      of NAD.

PMID- 25774719
TI  - Poly(ADP-ribose)--a unique natural polymer structural features, biological role
      and approaches to the chemical synthesis.
AB  - Poly(ADP-ribose) (PAR) is a natural polymer, taking part in numerous important
      cellular processes. Several enzymes are involved in biosynthesis and degradation
      of PAR. One of them, poly(ADP-ribose)polymerase-1 (PARP-1) is considered to be a
      perspective target for the design of new drugs, affecting PAR metabolism. The
      structure of PAR was established by enzymatic hydrolysis and further analysis of
      the products, but total chemical synthesis of PAR hasn't been described yet.
      Several approaches have been developed on the way to chemical synthesis of this
      unique biopolymer. 

PMID- 25774720
TI  - Towards metal-mediated g-quartet analogues: 1,2,4-triazole nucleotides.
AB  - We proposed that metal-coordinating nucleotides could be used to control the
      assembly of G-quadruplexes through the formation of an artificial metal-centered
      quartet. Several guanine-rich DNA sequences containing 1,2,4-triazole
      functionalized nucleotides were investigated. These oligonucleotides were
      designed to form quartets mediated by metal-triazole bonding both on the surface
      of and within the G-quadruplex core. In contrast to duplex studies in which 1,2,4
      triazole nucleosides serve as a mimic of Watson-Crick base-pairs, our results
      show that these nucleosides are not suitable components of an artificial metal
      centered quartet. 

PMID- 25774721
TI  - Synthesis of novel thiopurine pyranonucleosides: evaluation of their bioactivity.
AB  - We report the synthesis of novel thiopurine pyranonucleosides. Direct coupling of
      silylated 6-mercaptopurine and 6-thioguanine with the appropriate pyranoses 1a-e
      via Vorbruggen nucleosidation, gave the N-9 linked mercaptopurine 2a-e and
      thioguanine 4a-e nucleosides, while their N-7 substituted congeners 10a-e and 7a
      e, were obtained through condensation of the same acetates with 6-chloro and 2
      amino-6-chloropurines, followed by subsequent thionation. Nucleosides 3a-e, 5a-e,
      8a-e, and 11a-e were evaluated for their cytostatic activity in three different
      tumor cell proliferative assays.

PMID- 25774722
TI  - Level of male infertility in the Ghanaian city of Tema.
AB  - Infertility among couples is a sensitive issue in Ghana; females are mostly
      blamed. Most male infertility cases are generally due to low sperm counts
      (oligozoospermia), poor sperm quality - characterised by poor sperm motility
      (asthenozoospermia) - or a combination of both (oligoasthenozoospermia). This is
      a retrospective study from January 1995 to December 2005 which determined the
      level and type of male infertility in and around the city of Tema. Seminal fluid
      analysis reports of male clients who visited the Adom Medical Laboratory in Tema
      were extracted from laboratory data and analysed. Our study involved 2795 males
      in the age range of 24-36 years. In 1995, 75% of the total samples analysed had
      sperm concentrations ranging from 21 to 350 million sperms/ml and showed a
      decreasing trend to 41% in 2005. Samples with sperm concentrations below 20
      million sperms/ml in 1995 increased from 20.5% to 57.6% in 2005; those with
      active motility > 45% decreased from 27 (30.7%) in 1995 to zero (0%) in 2005,
      whilst samples with > 50% non-motile sperms increased from 47 (53.4%) in 1995 to
      449 (87.7%) in 2005. Male infertility in the samples analysed was due to a
      combination of oligozoospermia and asthenozoospermia. 

PMID- 25774723
TI  - [Not Available].

PMID- 25774724
TI  - [Not Available].

PMID- 25774725
TI  - [Not Available].

PMID- 25774726
TI  - [77-year-old female with temporal arteriitis, fever, exhaustion and cough].

PMID- 25774727
TI  - [A systemic disease with different etiologies: cardiac insufficiency].

PMID- 25774728
TI  - [Acute heart failure - a unique challenge].
AB  - Acute heart failure (AHF) is frequent, often life threatening and followed by
      emergency hospitalization. Leading symptoms are dyspnea, edema and fatigue. A
      broad spectrum of risk factors, cardiac diseases and comorbidities predisposes to
      AHF. Typical triggers (e. g. arrhythmias) modulate the individual clinical
      picture. Their misinterpretation may delay the diagnosis, which always needs to
      be ascertained by cardiac imaging (echocardiography). Rescue therapy aims at
      amelioration of symptoms and stabilization of vital parameters. In contrast to
      chronic heart failure evidence of the efficacy of available treatments is limited
      and in the past innovations have been sparse in this area. The clinical course is
      characterized by high short- and long-term mortality and repeat cardiac
      decompensations, but seamless multidisciplinary care and better knowledge and
      self-supervision on the patients' side might improve prognosis. Today, too little
      attention is paid to the palliative needs of patients with AHF. 

PMID- 25774729
TI  - [Diastolic heart failure and multimorbidity].
AB  - Heart failure is the most common reason for hospitalisation in Germany. About
      half of all heart failure cases are caused by "heart failure with preserved
      ejection fraction", i. e. "diastolic heart failure". Hemodynamic alterations are
      characterized by an increase in left ventricular stiffness, which leads to an
      increase in left ventricular filling pressures, especially during exercise.
      Numerous pathophysiologic changes can cause diastolic heart failure which may
      explain why it is so difficult to treat this disease. Comorbidities are more
      prevalent in diastolic heart failure as compared to heart failure with reduced
      ejection fraction. The most important comorbidities are discussed in terms of
      prevalence, relevance for outcome and therapeutic options. 

PMID- 25774730
TI  - [Treatment of chronic heart failure: what's not (yet) in the guidelines].
AB  - 2012 Scientific meeting of the European Society of Cardiology (ESC), the current
      Guidelines on Acute and Chronic Heart Failure were introduced whose preparation
      had started 18 months earlier. These guidelines integrate scientific evidence of
      the years 2011 and 2012, leaving several questions open due to gaps in knowledge.
      These questions relate, amongst others, to diagnostics and imaging, non
      pharmacologic and pharmacologic therapeutic approaches, mechanical support
      therapy, and heart transplantation. Based on recent studies, we will address some
      of these questions and discuss potential impact of their results on current
      clinical practice. A further official update of the ESC heart failure guidelines
      is expected for early 2016, which will then show if today's assessment holds
      true. 

PMID- 25774731
TI  - [Are disease management programs in Germany effective?].

PMID- 25774732
TI  - [How to do: transarterial chemoembolization (TACE)].
AB  - Transarterial Chemoembolization (TACE) is the standard procedure for intermediate
      stage hepatocellular carcinoma (HCC). TACE combines local chemotherapy with
      embolization of the arterially hypervascularisated HCC. In this article we
      present indication, contraindication, technical background, practical approach
      and side effect of TACE. 

PMID- 25774733
TI  - [Cardiogenic shock due to atypical Tako-Tsubo cardiomyopathy in a young woman
      with pheochromocytoma].
AB  - HISTORY AND CLINICAL FINDINGS: A 42-year old female patient was admitted in
      cardiogenic shock with pulmonary edema requiring prehospital intubation and
      mechanical ventilation. INVESTIGATIONS: | Emergency cardiac catheterization
      because of suspected acute coronary syndrome excluded coronary artery disease.
      Ventriculography and echocardiography suggested an inverse Tako-Tsubo
      cardiomyopathy with akinesia of the basal left ventricular myocardium and only
      apical preserved wall motion. TREATMENT AND COURSE: Under intensive care therapy
      with mechanical ventilation, inotropic support, infusion of saline and
      intraaortal balloon pumping, left ventricular function improved. After
      discontinuation of mechanical ventilation and discharge from ICU, the patient
      repeatedly suffered from panic attacks. She was therefore transferred to a
      psychosomatic center. There she exhibited repeated hypertensive crisis.
      Ultrasound of the kidney showed an adrenal mass. Together with elevated plasma
      catecholamines, the diagnosis of pheochromocytoma was suspected. This could be
      proved by magnetic resonance imaging. After surgical removement of the adrenal
      mass, the patient was free of symptoms.

PMID- 25774734
TI  - [Pulmonary infection in neutropenia].
AB  - MEDICAL HISTORY AND CLINICAL COURSE: A 42-year-old patient with hairy cell
      leukemia had been treated for 3 years by a hematologist in private practice.
      Initially the patient received 1 course of cladribine upon which the disease went
      into complete remission. 6 weeks ago a relapse was diagnosed and combination
      therapy with cladibrin and rituximab was initiated. Now the patient presented to
      the emergency room with shortness of breath and pain when breathing.
      INVESTIGATIONS, TREATMENT AND COURSE: In the chest x-ray, patchy infiltrates and
      pleural effusions were found on both sides. The subsequently performed computed
      tomography showed bilateral compactions with an Halo suspicious for fungal
      infiltrates. Upon admission to the hospital, an empirical antibiotic therapy with
      clarithromycin and piperacillin/tazobactam was initiated, which was later
      escalated to meropenem and linezolid. Additionally, an antifungal therapy with
      voriconazole was started and later switched to liposomal amphotericin B. At his
      admission, a positive aspergillus antigen could be detected in the
      microbiological laboratory. Under antimycotic treatment the aspergillus antigen
      was repeatedly negative. The patient presented with pronounced cytopenias and
      after a switch of therapy to vemurafenib and filgrastim, the hematopoiesis could
      only be stimulated insufficiently. The patient was transferred to the intensive
      care unit three days after admission with severe respiratory failure. He died on
      day 8 after admission. AUTOPSY AND DIAGNOSIS: Diagnosis was consistent with
      relapse of hairy cell leukemia with positive BRAF mutation and a bone marrow
      infiltration > 80 %. Autopsy revealed a significant hepato-splenomegaly, a lack
      of erythro-, granulo- and thrombopoiesis. Clots interspersed with fungal hyphae
      were found in both lungs and an infarction of the spleen with evidence of fungal
      hyphae was detected. The cultural findings post mortem on yeast or mold were
      negative. CONCLUSION: Patients with refractory hairy cell leukemia and prolonged
      neutropenia are at increased risk for systemic fungal infections. Therefore,
      prohylactic antimycotic therapy should be considered early in this group of
      patients. The therapeutic approach of vemurafenib in treatment-refractory hairy
      cell leukemia is promising and offers an additional treatment option. In the
      present case, the patient could unfortunately not be stabilized due to the septic
      complications.

PMID- 25774735
TI  - [Tropheryma whipplei: pathogen of Whipple's disease and more].
AB  - Within the last years the understanding of infection with Tropheryma whipplei was
      significantly enhanced by improvement of molecular biology, microbiology and
      immunology. The following entities of infection or carriage, respectively, with
      T. whipplei must be differentiated: besides in the context of classical Whipple's
      disease (CWD), the rare chronic infection with T. whipplei (estimated incidence:
      1 : 1,000,000), T. whipplei can be detected more frequently in stool specimens of
      children with acute gastroenteritis or asymptomatic carriers, or as a cause of
      isolated endocarditis. However, infection with T. whipplei only rarely results in
      CWD. T. whipplei was well characterized, raised in vitro and its genome
      completely sequenced within the last two decades. Very interesting is the
      resistance of the agent against glutaraldehyde.The histological detection within
      duodenal biopsies with "Periodic Acid Schiff" (PAS) staining still is first
      choice for the diagnosis of CWD. Today PCR or immunohistochemistry can identify
      the agent more specifically. In cases of isolated organ manifestations of e. g.
      joints or central nervous system the agent needs to be identified from specimen
      from the affected sites. Successful treatment can be achieved in most of the
      cases by antimicrobial therapy and first prospective treatment trials are
      published. However, neuronal CWD still can be progressive lethal and an immune
      reconstitution inflammatory syndrome (IRIS) might complicate the course of
      treatment and in worst case end fatal. Thus, because of the complexity of the
      disease a specialised reference centre should be consulted for diagnosis and
      treatment of CWD. 

PMID- 25774736
TI  - [SPECT/CT: Benefit and indications of hybrid imaging].

PMID- 25774737
TI  - [Do we use the wrong target value for the supportive therapy of sepsis?].
AB  - Sepsis is a generalized, usually infectious disease with a complex dsyregulated
      immune response and capillary leak. The leakage leads to a severe drop of blood
      pressure with hypoperfusion and sympathetic counterregulation. The lung is
      frequently involved either as a source of the inflammation or by emergence of an
      ARDS, both resulting into severe hypoxemia. The supportive therapy is used to
      stabilize the hemodynamics and to keep the target value partial pressure of
      arterial oxygen (PaO2) in the lower limit of normal. Pathophysiologically it is
      not plausible to define hypoxemia on the basis of PaO2 or SaO2, because the
      supply of the cells is determined by the amount of oxygen molecules. This is
      mirrored by the oxygen content (CaO2) and the hemodynamic transport, the cardiac
      output. As far as data about the hypoxic tolerance of organs are available, the
      critical value respective the threshold for anaerobic metabolism is 5-10 folds
      lower than values achieved by application of current guidelines. If CaO2 would be
      used as the target value, a lot of measures aiming for normoxia, which
      potentially harm patients, could be avoided. Among these measures are high, often
      toxic inspiratory concentrations of oxygen, high ventilation pressure, dangerous
      body position changes and excessive volume administration. It is not surprising,
      that there are no plausible data in the literature which have shown a positive
      effect for the target value PaO2 or SaO2. Studies are urgent needed to compare
      CaO2 as a target value to the standards in the current guidelines. Additional
      animal experiments should be done to get information on the critical range of
      CaO2, in order to translate these results into treatment strategies for intensive
      care unit patients with severe hypoxemia.

PMID- 25774738
TI  - [Predictive value of congress abstracts for later publication: Analysis of the
      the congresses 2006-2010 of the German Cardiac Society].
AB  - AIMS: The present study investigates whether scientific abstracts, which were
      accepted for presentation at the annual meeting of the German Cardiac Society
      (DGK) will be published more frequently and with higher ranking than rejected
      abstracts. Additionally, we analyzed whether the current peer review process of
      the congress abstracts is able to identify research of high quality. METHODS: All
      abstracts submitted for the DGK meetings between 2006 and 2010 were anonymized
      and graded by 5-9 reviewers. Based on these ratings, abstracts were accepted or
      rejected. A Medline search with name of the first author, key words and content
      of all abstracts was conducted to identify publications following the congress
      abstracts. In case of identification of a publication, the impact factor (IF) of
      the journal was assessed. RESULTS: 5535 (66 %) of 8411 submitted abstracts were
      accepted for presentation (basic reseach: 2497; clinical study: 5914). A total of
      23 % of all abstracts were published (IF 3.6). The average time to publication
      was 0.7 +/- 1.2 years, while 35 % of all published studies achieved publication
      in the year of congress. The publication rate was 26 % for accepted abstracts (IF
      3.8) and 17 % (2.4) for rejected abstracts. Basic research achieved higher
      publication rates than clinical studies (26 % vs. 21 %) and had a higher average
      impact factor (IF 5.1 vs. 3). CONCLUSIONS: The present study shows that
      abstracts, which were accepted for presentation achieved a publication more
      frequently and in higher-ranked journals than rejected abstracts.

PMID- 25774739
TI  - [Ambulatory care of patients with asthma in Germany and disease management
      program for asthma from the view of statutory health insured patients. A postal
      survey of statutory health insured patients].
AB  - BACKGROUND: In spite of a decline in mortality due to asthma in Germany various
      studies point towards deficits in asthma care. Our investigation should collect
      data about ambulatory care from the view of statutory health insured patients
      (SHI), who participate in the disease management program asthma (DMP-P) or do not
      (NP). Primary question was, if there is a difference between asthma control.
      Secondary questions referred to process parameters. METHODS: The postal inquiry
      was conducted in 2010 with 8000 randomly selected members of a SHI company with
      asthma (4000 DMP-P and 4000 NP). The descriptive evaluation of categorical items
      was performed with cross-tables. The absolute risk reduction (ARR) and 97.5 %
      confidence interval (CI; multiple level 5 %) was used to evaluate the primary
      question. Secondary questions were analysed by ARR and 95 %-CI. RESULTS: The
      response rate of the questionnaire accounted for 31.1 % (2565). 49.2 % of all
      respondents lived with an uncontrolled asthma with no differences between DMP-P
      and NP (ARR -2.7 %, 97.5 %-CI -7.9 -2.4 %). Results did not alter after
      adjustment for sex and age. The secondary questions revealed significant
      differences (DMP-P vs. NP) in participation in asthma trainings 50.6 vs. 32.3 %,
      use of a peak-flow-meter 49.3 vs. 25.3 % and asthma action plan within reach 21.7
      vs. 11.0 %. CONCLUSION: Half of all respondents lives selfreported - even in the
      DMP-group - with an uncontrolled asthma. Process parameters showed better results
      in the DMP-group. It can be considered, that the DMP has its desired effect on
      patient-centered care, but does not lead to a better therapeutic outcome.
      Explanations can only be assumed: insufficient impact of the process parameters
      on the outcome, patient behavior, that minimizes a possible effect, or selection
      effects, if patients, who were more sick and at the same time more motivated,
      were mainly included in the DMP. These aspects should be addressed in studies
      with a prospective design.

PMID- 25774741
TI  - A risk-adjusted, composite outcomes score and resource utilization metrics for
      very low-birth-weight infants.
AB  - IMPORTANCE: It is difficult for neonatal intensive care units (NICUs) to
      determine the overall efficacy of multiple continuous quality improvement (CQI)
      projects aimed at reducing very low-birth-weight (VLBW) infant morbidities. It is
      challenging to know whether a NICU is becoming more proficient, and it is not
      usually apparent whether concurrent resource use is changing. OBJECTIVE: To
      develop a risk-adjusted composite score of the major morbidities in VLBW infants
      and a companion metric that accounts for resource use to enhance the ability to
      measure overall progress in CQI and to identify proficient NICUs. DESIGN,
      SETTING, AND PARTICIPANTS: This retrospective investigation used individual
      patient-level demographic and outcomes data from 8 NICUs who were long term CQI
      collaborators within the Vermont Oxford Network, a large international quality
      improvement organization dedicated to improving the care of premature infants.
      Study participants were infants who weighed 401 to 1500 g born from January 1,
      2000, through December 31, 2011, at each of the 8 participating NICUs. MAIN
      OUTCOMES AND MEASURES: Risk-adjusted, composite VLBW infant morbidity and
      resource utilization score. RESULTS: A total of 15,961 infants (mean [SD]
      gestational age, 28.2 [3.0] weeks; mean [SD] birth weight, 1020 [306] g) were
      analyzed. Concurrent with multiple shared CQI projects over 12 years, the group
      benefit metric improved 38% from 80 in 2000 to 110 in 2011 (P < .001). The entire
      member VON benefit metric improved 28% from 72 in 2000 to 92 in 2011 (P < .001).
      The group value metric improved 25% from 1.2 in 2000 to 1.5 in 2011 (P < .001).
      The entire member VON value metric improved 18% from 1.1 in 2000 to 1.3 in 2011
      (P < .001). Significant inter-NICU variation in both composite scores was noted
      in the 8 member CQI group. Hospital length of stay increased in the 8 NICUs 64 to
      71 days (P <.001), and a similar increase was noted in the entire member VON, 65
      to 68 days (P < .001). CONCLUSIONS AND RELEVANCE: We have created the first, to
      our knowledge, web-based tool for NICUs to calculate their own composite
      morbidity and resource utilization scores that estimate NICU CQI proficiency. In
      our structured group CQI over 12 years, both metrics revealed significant
      improvement, but increases in length of stay (resource use) blunted value
      improvement. Why some NICUs improve their scores more successfully than others
      remains a crucial challenge. Future CQI efforts should explore strategies that
      cost-efficiently reduce intertwined VLBW infant morbidities, emphasizing whole
      cultures of proficient care rather than the traditional emphasis on single
      morbidity reduction.

PMID- 25774740
TI  - Rational stabilization of complex proteins: a divide and combine approach.
AB  - Increasing the thermostability of proteins is often crucial for their successful
      use as analytic, synthetic or therapeutic tools. Most rational
      thermostabilization strategies were developed on small two-state proteins and,
      unsurprisingly, they tend to fail when applied to the much more abundant, larger,
      non-fully cooperative proteins. We show that the key to stabilize the latter is
      to know the regions of lower stability. To prove it, we have engineered
      apoflavodoxin, a non-fully cooperative protein on which previous
      thermostabilizing attempts had failed. We use a step-wise combination of
      structure-based, rationally-designed, stabilizing mutations confined to the less
      stable structural region, and obtain variants that, according to their van't Hoff
      to calorimetric enthalpy ratios, exhibit fully-cooperative thermal unfolding with
      a melting temperature of 75 degrees C, 32 degrees above the lower melting
      temperature of the non-cooperative wild type protein. The ideas introduced here
      may also be useful for the thermostabilization of complex proteins through
      formulation or using specific stabilizing ligands (e.g. pharmacological
      chaperones). 

PMID- 25774742
TI  - Comparing computer adaptive and curriculum-based measures of math in progress
      monitoring.
AB  - The purpose of the study was to compare the use of a Computer Adaptive Test and
      Curriculum-Based Measurement in the assessment of mathematics. This study also
      investigated the degree to which slope or rate of change predicted student
      outcomes on the annual state assessment of mathematics above and beyond scores of
      single point screening assessments (i.e., the computer adaptive test or the CBM
      assessment just before the administration of the state assessment). Repeated
      measurement of mathematics once per month across a 7-month period using a
      Computer Adaptive Test (STAR-Math) and Curriculum-Based Measurement (CBM, AIMSweb
      Math Computation, AIMSweb Math Concepts/Applications) was collected for a maximum
      total of 250 third, fourth, and fifth grade students. Results showed STAR-Math in
      all 3 grades and AIMSweb Math Concepts/Applications in the third and fifth grades
      had primarily linear growth patterns in mathematics. AIMSweb Math Computation in
      all grades and AIMSweb Math Concepts/Applications in Grade 4 had decelerating
      positive trends. Predictive validity evidence showed the strongest relationships
      were between STAR-Math and outcomes for third and fourth grade students. The
      blockwise multiple regression by grade revealed that slopes accounted for only a
      very small proportion of additional variance above and beyond what was explained
      by the scores obtained on a single point of assessment just prior to the
      administration of the state assessment.

PMID- 25774743
TI  - On the undiffusion of established practices.

PMID- 25774744
TI  - Formal and informal organizational activities of people who inject drugs in New
      York City: description and correlates.
AB  - Little is known about group memberships of people who inject drugs (PWID). Three
      hundred PWID were interviewed about formal and informal group participation and
      risk behaviors. Many took part in groups related to problems and resources
      associated with injecting drugs, religion, sports or gender. Harm reduction group
      and support group participation was associated with less risk behavior; sports
      groups participation with more risk behavior. Group involvement by PWID may be
      important to their lives and/or affect prevention or infectious disease
      transmission. More research is needed about determinants and consequences of
      their and other drug users' group memberships. 

PMID- 25774745
TI  - Is children's reading "good enough"? Links between online processing and
      comprehension as children read syntactically ambiguous sentences.
AB  - We monitored 8- and 10-year-old children's eye movements as they read sentences
      containing a temporary syntactic ambiguity to obtain a detailed record of their
      online processing. Children showed the classic garden-path effect in online
      processing. Their reading was disrupted following disambiguation, relative to
      control sentences containing a comma to block the ambiguity, although the
      disruption occurred somewhat later than would be expected for mature readers. We
      also asked children questions to probe their comprehension of the syntactic
      ambiguity offline. They made more errors following ambiguous sentences than
      following control sentences, demonstrating that the initial incorrect parse of
      the garden-path sentence influenced offline comprehension. These findings are
      consistent with "good enough" processing effects seen in adults. While faster
      reading times and more regressions were generally associated with better
      comprehension, spending longer reading the question predicted comprehension
      success specifically in the ambiguous condition. This suggests that reading the
      question prompted children to reconstruct the sentence and engage in some form of
      processing, which in turn increased the likelihood of comprehension success.
      Older children were more sensitive to the syntactic function of commas, and,
      overall, they were faster and more accurate than younger children. 

PMID- 25774746
TI  - Identification and characterization of a novel gene encoding the NBS1 protein in
      Pyricularia oryzae.
AB  - The ascomycete Pyricularia oryzae (teleomorph: Magnaporthe oryzae) causes one of
      the most serious diseases known as rice blast. The Nijmegen breakage syndrome
      protein (NBS1) is essential for DNA repair; thus, we studied the P. oryzae NBS1
      homolog (PoNBS1). A PoNBS1 null mutant exhibited high sensitivity to DNA damage
      inducing agents. The mutant also exhibited the retarded hyphal growth, and
      induced abnormal conidial germination and shape, but showed normal appressorium
      formation. The phenotypes of the null mutant were complemented by introducing the
      cDNA of PoNBS1 driven by a TrpC promoter of Aspergillus nidulans. In addition,
      the null mutant similarly complemented with the PoNBS1 cDNA lacking the FHA
      domain that had a normal phenotype except for hyphal growth. These results
      suggest that PoNBS1 is involved in DNA repair and normal development in P.
      oryzae. Moreover, the FHA domain of PoNBS1 participates in normal hyphal growth. 

PMID- 25774747
TI  - Dialysis modality and survival: does the controversy live on?
AB  - PURPOSE OF REVIEW: Continued debate regarding the relative mortality risk for end
      stage renal disease patients treated with either peritoneal dialysis or facility
      based three times weekly conventional haemodialysis (CHD) stems from the absence
      of adequately powered randomized controlled trials, and the reliance on
      observational studies. These reports have yielded important trends, but also
      conflicting results. Here, we summarize the contemporary literature on survival
      comparisons between CHD and peritoneal dialysis, highlighting trends and
      important differences between studies. RECENT FINDINGS: Large observational
      studies have not conclusively shown an overall survival advantage of either
      dialysis modality. Studies have consistently shown an early survival advantage
      for peritoneal dialysis relative to CHD. New insights including accounting for
      selection bias and the use of central venous catheters as incident haemodialysis
      access may explain much of this apparent early mortality difference. The relative
      mortality risk of peritoneal dialysis versus haemodialysis may be decreasing in
      more contemporary cohorts. Older patients, diabetic patients, and those with
      comorbidities may have a relatively worse prognosis on peritoneal dialysis
      compared to CHD. SUMMARY: Overall, survival of incident end-stage renal disease
      patients is similar for CHD and peritoneal dialysis, but early survival
      differences may be driven by selection bias. Decisions regarding modality choice
      should be individualized, considering other important patient outcomes including
      quality of life. Whereas a future randomized controlled trial is ideally suited
      to address this question, practical limitations may continue to limit its
      development.

PMID- 25774748
TI  - Risk factors for progression in ADPKD.
AB  - PURPOSE OF REVIEW: Autosomal dominant polycystic kidney disease (ADPKD) is the
      most common hereditary kidney disease. This article will describe the factors
      associated with both functional and structural evidence of disease progression.
      It will also review the results of recent clinical trials that have shown an
      impact on markers of disease progression. RECENT FINDINGS: A variety of
      prognostic factors have been described that relate to a decline in glomerular
      filtration rate or an increase in total cyst or kidney volumes. We now have
      clinical trials that show that glomerular filtration rate decline and kidney
      volume growth can be slowed in those with ADPKD. SUMMARY: With the emergence of
      potential disease-modifying therapies, factors that can accurately identify those
      who are most at risk for renal progression or ADPKD-related complications need to
      be identified and validated.

PMID- 25774750
TI  - Paradoxical hemodynamic collapse after subxiphoid pericardial window.
AB  - A 56-year-old man with a history of coronary artery disease, 4 months of cough
      and shortness of breath, a new lung mass, and increasing hypoxemia presented to
      the operating room emergently for a subxiphoid pericardial window for cardiac
      tamponade. After 1200 mL of pericardial fluid was drained, the patient
      immediately went into acutely decompensated right heart failure as seen on a
      transesophageal echocardiogram. The patient had cardiovascular collapse
      refractory to high-dose vasopressors, necessitating emergent venous-arterial
      extracorporeal membrane oxygenation for successful resuscitation. 

PMID- 25774751
TI  - Major pneumocephalus after lung resection.
AB  - We present the case of a 62-year-old woman with an advanced metastatic lung tumor
      that required palliative debulking. Perioperative placement of a surgical clip in
      the dura of the thoracic spinal cord caused a dural breach, which ultimately
      caused a pneumocephalus. An awareness of this association is important,
      especially in patients undergoing thoracic resections. We also describe our
      approach to the management of this condition. 

PMID- 25774752
TI  - Utility of intraoperative lung ultrasonography.
AB  - A patient with an endobronchial tumor and critical airway obstruction developed
      hypoxia and hypercarbia and, subsequently, cardiac arrest during a palliative
      laser core-out excision. The differential diagnosis included tension
      pneumothorax, as well as airway obstruction due to swelling of residual tumor or
      to blood clots. In this case, empiric needle decompression could have had
      deleterious consequences. Immediate bedside lung ultrasonography provided real
      time information leading to the stabilization of the patient. This case provides
      compelling motivation for anesthesiologists to acquire this easily learned skill.

PMID- 25774749
TI  - Hyperbilirubinemia exaggerates endotoxin-induced hypothermia.
AB  - Systemic inflammation is accompanied by an increased production of reactive
      oxygen species (ROS) and by either fever or hypothermia (or both). To study
      aseptic systemic inflammation, it is often induced in rats by the intravenous
      administration of bacterial lipopolysaccharide (LPS). Knowing that bilirubin is a
      potent ROS scavenger, we compared responses to LPS between normobilirubinemic
      Gunn rats (heterozygous, asymptomatic; J/+) and hyperbilirubinemic Gunn rats
      (homozygous, jaundiced; J/J) to establish whether ROS mediate fever and
      hypothermia in aseptic systemic inflammation. These two genotypes correspond to
      undisturbed versus drastically suppressed (by bilirubin) tissue accumulation of
      ROS, respectively. A low dose of LPS (10 MUg/kg) caused a typical triphasic fever
      in both genotypes, without any intergenotype differences. A high dose of LPS
      (1,000 MUg/kg) caused a complex response consisting of early hypothermia followed
      by late fever. The hypothermic response was markedly exaggerated, whereas the
      subsequent fever response was strongly attenuated in J/J rats, as compared to J/+
      rats. J/J rats also tended to respond to 1,000 MUg/kg with blunted surges in
      plasma levels of all hepatic enzymes studied (alanine aminotransferase, aspartate
      aminotransferase, gamma-glutamyl transferase), thus suggesting an attenuation of
      hepatic damage. We propose that the reported exaggeration of LPS-induced
      hypothermia in J/J rats occurs via direct inhibition of nonshivering
      thermogenesis by bilirubin and possibly via a direct vasodilatatory action of
      bilirubin in the skin. This hypothermia-exaggerating effect might be responsible,
      at least in part, for the observed tendency of J/J rats to be protected from LPS
      induced hepatic damage. The attenuation of the fever response to 1,000 MUg/kg
      could be due to either direct actions of bilirubin on thermoeffectors or the ROS
      scavenging action of bilirubin. However, the experiments with 10 MUg/kg strongly
      suggest that ROS signaling is not involved in the fever response to low doses of
      LPS.

PMID- 25774753
TI  - Superimposed cocaine-induced rhabdomyolysis in a patient with aortic dissection
      rhabdomyolysis.
AB  - A 52-year-old man presented with acute, sharp chest pain radiating to the back
      and abdomen after using cocaine 18 hours previously. Computed tomographic
      angiography revealed a type B aortic dissection that extended to the iliac
      arteries. The patient underwent balloon fenestration, placement of multiple
      aortic stents, and bilateral leg fasciotomy. He eventually went into hyperkalemic
      arrest but was successfully resuscitated, after which his serum lactate and
      creatine kinase levels peaked at 7.4 mmol/L and 990,400 U/L, respectively. The
      combination of aortic dissection and creatine kinase toxicity was extensive
      enough to cause permanent renal failure and paraplegia below T6. The severity of
      the patient's symptoms was attributed to concomitant cocaine-induced
      rhabdomyolysis and aortic dissection rhabdomyolysis. 

PMID- 25774754
TI  - Embedding research culture and productivity in hospital physiotherapy
      departments: challenges and opportunities.
AB  - Few studies have investigated research culture in the Australian hospital system.
      Although physiotherapists working in tertiary hospital departments conduct and
      publish research, a conflict between service delivery and research productivity
      remains. Few departments record research achievements, which limits the accuracy
      of investigating factors associated with research productivity within allied
      health. The conduct and translation of research within acute physiotherapy and
      allied health departments is imperative to improve patient health outcomes,
      optimise health service efficiency and cost-effectiveness and to improve staff
      and patient satisfaction and staff retention. Allied health departments should
      institute a research register and consider implementing other strategies to
      improve research culture and productivity, such as dedicating equivalent full
      time staff to research, supporting staff with joint clinical and academic
      appointments, ensuring a research register is available and used and having
      events available for the dissemination of research. Future research should focus
      on improving research productivity within acute allied health departments to
      provide Level 1 and 2 evidence of service effectiveness and cost-effectiveness to
      optimise health care delivery and to maximise the benefit of allied health staff
      to Australia's healthcare system.

PMID- 25774755
TI  - An evaluation of self-esteem and quality of life in orthodontic patients: effects
      of crowding and protrusion.
AB  - OBJECTIVE: To evaluate the effect of dental crowding and lip protrusion on self
      esteem and quality of life (QOL) in female orthodontic patients with Class I
      malocclusion. MATERIALS AND METHODS: The study sample consisted of 201 patients
      (mean age 22.6 +/- 3.0 years) who sought orthodontic treatment. All the patients
      were evaluated before treatment in terms of their degree of dental crowding and
      lip protrusion. Rosenberg's Self-Esteem Scale and the Orthognathic Quality of
      Life Questionnaire (OQLQ) were used to determine self-esteem and QOL and to
      evaluate whether these values were related to malocclusion severity. RESULTS: The
      results indicated that severe crowding and severe protrusion can result in lower
      self-esteem and poorer QOL (P < .05) than mild crowding and protrusion in Class I
      malocclusion. In the oral function component of the OQLQ, the severity of
      protrusion did not have significant effect. CONCLUSIONS: In Class I malocclusion,
      patients with mild crowding or protrusion had significantly better self-esteem
      and QOL scores than severe crowding or protrusion patients.

PMID- 25774756
TI  - Impact of Dietary Acculturation on the Food Habits, Weight, Blood Pressure, and
      Fasting Blood Glucose Levels of International College Students.
AB  - OBJECTIVE: This study was conducted to determine the impact of dietary
      acculturation on the health status of newly arrived international students at
      Virginia Tech in Fall 2010. PARTICIPANTS: Thirty-five international students, 18
      36 years of age, completed the study. METHODS: Data were collected at 3 different
      time periods (V1, V2, and V3) approximately 6 weeks apart. A food frequency- and
      dietary pattern-related questionnaire was administered and numerically coded
      responses were analyzed. Twenty-four-hour dietary recall data were also collected
      at V1, V2, and V3. Body weight, fasting blood glucose level, and blood pressure
      of study participants were also determined at each time period. RESULTS: Total
      sample population (TSP) had a significant increase in mean weight of 2.79 lb from
      visit 1 (V1) to visit 3 (V3) (p = .0082). Ten participants gained an average of
      9.0 lb (participants who gained weight; n = 10). There was also an increase in
      the frequency of consumption of high-calorie American food items from V1 to V3.
      However, there were no significant changes in mean systolic blood pressure and
      mean fasting blood glucose was significantly lower at V3 than at V1. CONCLUSIONS:
      There was a gradual shift in the dietary patterns of international students
      towards the American diet. Dietary acculturation led to weight gain among some of
      the students, which may potentially have a negative impact on their health status
      if continued for longer time periods.

PMID- 25774757
TI  - Genome editing using TALENs in blind Mexican Cavefish, Astyanax mexicanus.
AB  - Astyanax mexicanus, a teleost fish that exists in a river-dwelling surface form
      and multiple cave-dwelling forms, is an excellent system for studying the genetic
      basis of evolution. Cavefish populations, which independently evolved from
      surface fish ancestors multiple times, have evolved a number of morphological and
      behavioral traits. Quantitative trait loci (QTL) analyses have been performed to
      identify the genetic basis of many of these traits. These studies, combined with
      recent sequencing of the genome, provide a unique opportunity to identify
      candidate genes for these cave-specific traits. However, tools to test the
      requirement of these genes must be established to evaluate the role of candidate
      genes in generating cave-specific traits. To address this need, we designed
      transcription activator-like effector nucleases (TALENs) to target two genes that
      contain coding changes in cavefish relative to surface fish and map to the same
      location as QTL for pigmentation, oculocutaneous albinism 2 (oca2) and
      melanocortin 1 receptor (mc1r). We found that surface fish genes can be mutated
      using this method. TALEN-induced mutations in oca2 result in mosaic loss of
      melanin pigmentation visible as albino patches in F0 founder fish, suggesting
      biallelic gene mutations in F0s and allowing us to evaluate the role of this gene
      in pigmentation. The pigment cells in the albino patches can produce melanin upon
      treatment with L-DOPA, behaving similarly to pigment cells in albino cavefish and
      providing additional evidence that oca2 is the gene within the QTL responsible
      for albinism in cavefish. This technology has the potential to introduce a
      powerful tool for studying the role of candidate genes responsible for the
      evolution of cavefish traits. 

PMID- 25774758
TI  - Linking abeta42-induced hyperexcitability to neurodegeneration, learning and
      motor deficits, and a shorter lifespan in an Alzheimer's model.
AB  - Alzheimer's disease (AD) is the most prevalent form of dementia in the elderly.
      beta-amyloid (Abeta) accumulation in the brain is thought to be a primary event
      leading to eventual cognitive and motor dysfunction in AD. Abeta has been shown
      to promote neuronal hyperactivity, which is consistent with enhanced seizure
      activity in mouse models and AD patients. Little, however, is known about
      whether, and how, increased excitability contributes to downstream pathologies of
      AD. Here, we show that overexpression of human Abeta42 in a Drosophila model
      indeed induces increased neuronal activity. We found that the underlying
      mechanism involves the selective degradation of the A-type K+ channel, Kv4. An
      age-dependent loss of Kv4 leads to an increased probability of AP firing.
      Interestingly, we find that loss of Kv4 alone results in learning and locomotion
      defects, as well as a shortened lifespan. To test whether the Abeta42-induced
      increase in neuronal excitability contributes to, or exacerbates, downstream
      pathologies, we transgenically over-expressed Kv4 to near wild-type levels in
      Abeta42-expressing animals. We show that restoration of Kv4 attenuated age
      dependent learning and locomotor deficits, slowed the onset of neurodegeneration,
      and partially rescued premature death seen in Abeta42-expressing animals. We
      conclude that Abeta42-induced hyperactivity plays a critical role in the age
      dependent cognitive and motor decline of this Abeta42-Drosophila model, and
      possibly in AD. 

PMID- 25774760
TI  - Genetic Lineages and Antimicrobial Resistance in Pseudomonas spp. Isolates
      Recovered from Food Samples.
AB  - Raw food is a reservoir of Pseudomonas isolates that could be disseminated to
      consumers. The presence of Pseudomonas spp. was studied in food samples, and the
      phenotypic and genotypic characterizations of the recovered isolates were
      analyzed. Two samples of meat (3%, turkey and beef) and 13 of vegetables (22%, 7
      green peppers and 6 tomatoes) contained Pseudomonas spp. A total of 20 isolates
      were identified, and were classified as follows (number of isolates): P.
      aeruginosa (5), P. putida (5), P. nitroreducens (4), P. fulva (2), P. mosselli
      (1), P. mendocina (1), P. monteilii (1), and Pseudomonas sp. (1). These 20
      Pseudomonas isolates were clonally different by pulsed-field-gel-electrophoresis,
      and were resistant to the following antibiotics: ticarcillin (85%), aztreonam
      (30%), cefepime (10%), imipenem (10%), and meropenem (5%), but were susceptible
      to ceftazidime, piperacillin, piperacillin-tazobactam, doripenem, gentamicin,
      tobramycin, amikacin, ciprofloxacin, norfloxacin, and colistin. Only one strain
      (Ps158) presented a class 1 integron lacking the 3' conserved segment. The five
      P. aeruginosa strains were typed by multilocus sequence typing in five different
      sequence-types (ST17, ST270, ST800, ST1455, and ST1456), and different mutations
      were detected in protein OprD that were classified in three groups. One strain
      (Ps159) showed a new insertion sequence (ISPa47) truncating the oprD gene, and
      conferring resistance to imipenem. 

PMID- 25774761
TI  - Beyond narrative: Is there an implicit structure to the way in which adults
      organise their discourse?
AB  - Understanding the structure of discourse in healthy adults is fundamental to the
      assessment and diagnosis of discourse level impairments in clinical populations
      and the development of effective treatment regimes. Exploring discourse genre in
      healthy speakers that extend beyond the traditional narrative is equally
      paramount in facilitating maximum impact of clinical interventions in everyday
      speaking contexts. This study aimed to characterise the discourse of 30 healthy
      adult speakers across three age groups (20-39, 40-59 and 60+ years) and four
      discourse genres (recount, procedural, exposition and narrative), drawing on
      discourse frameworks used in classroom teaching. A clinically useful discourse
      protocol and analytic procedure using SALT was developed that profiled the
      macrostructure and key aspects of linguistic microstructure of the different
      genres, exploring coherence and cohesion within and across genre in a systematic
      manner. Analyses considered whether there were differences in coherence and
      cohesion among the different age groups, different genres and specific topics.
      Results showed that, while individual variability was present, healthy adults
      structured their discourse consistently, adhering to the frameworks described in
      the developmental literature, across all four genres. Significant age differences
      were only seen in the amount of information contained in the body of the
      discourse (i.e. events, steps or statements offered) with older participants
      offering less information. This dataset will enable comparisons to be drawn with
      clinical populations to determine the utility and the feasibility of the use of
      this framework for diagnosis and intervention. 

PMID- 25774762
TI  - Speech production in children with Down's syndrome: The effects of reading,
      naming and imitation.
AB  - People with DS are known to have difficulties with expressive language, and often
      have difficulties with intelligibility. They often have stronger visual than
      verbal short-term memory skills and, therefore, reading has often been suggested
      as an intervention for speech and language in this population. However, there is
      as yet no firm evidence that reading can improve speech outcomes. This study
      aimed to compare reading, picture naming and repetition for the same 10 words, to
      identify if the speech of eight children with DS (aged 11-14 years) was more
      accurate, consistent and intelligible when reading. Results show that children
      were slightly, yet significantly, more accurate and intelligible when they read
      words compared with when they produced those words in naming or imitation
      conditions although the reduction in inconsistency was non-significant. The
      results of this small-scale study provide tentative support for previous claims
      about the benefits of reading for children with DS. The mechanisms behind a
      facilitatory effect of reading are considered, and directions are identified for
      future research. 

PMID- 25774764
TI  - Complexity markers in morphosyntactic productions in French-speaking children
      with specific language impairment (SLI).
AB  - The usage-based theory considers that the morphosyntactic productions of children
      with SLI are particularly dependent on input frequency. When producing complex
      syntax, the language of these children is, therefore, predicted to have a lower
      variability and to contain fewer infrequent morphosyntactic markers than that of
      younger children matched on morphosyntactic abilities. Using a spontaneous
      language task, the current study compared the complexity of the morphological and
      structural productions of 20 children with SLI and 20 language-matched peers
      (matched on both morphosyntactic comprehension and mean length of utterance). As
      expected, results showed that although basic structures were produced in the same
      way in both groups, several complex forms (i.e. tenses such as Imperfect, Future
      or Conditional and Conjunctions) were less frequent in the productions of
      children with SLI. Finally, we attempted to highlight complex linguistic forms
      that could be good clinical markers for these children. 

PMID- 25774763
TI  - From aardvark to ziggurat: A new tool for assessing children's use of rare
      vocabulary.
AB  - This study introduces a resource for examining children's use of low-frequency
      vocabulary and describes preliminary evidence of its validity. Using a corpus of
      >1400 transcripts from school-aged children, we derived a concordance of all
      words spoken by the children and generated a list of 2079 uncommon words we have
      called WERVE, the Wordlist for Expressive Rare Vocabulary Evaluation. Preliminary
      validity evidence for WERVE was examined through correlation analyses with WERVE
      results and other common language measures in a test sample of 112 children age 7
      and 8 years. In addition, we replicated the correlation analyses using a sample
      of 38 eight-year-old children. WERVE results correlated strongly with established
      language sample measures and to a lesser but frequently significant degree with
      standardized test results. Results also showed developmental change from age 7 to
      age 8. Correlations ranged from medium to large. These results suggest that WERVE
      may be a useful tool for language sample researchers to explore. 

PMID- 25774766
TI  - The effect of phylogenetically different bacteria on the fitness of Pseudomonas
      fluorescens in sand microcosms.
AB  - In most environments many microorganisms live in close vicinity and can interact
      in various ways. Recent studies suggest that bacteria are able to sense and
      respond to the presence of neighbouring bacteria in the environment and alter
      their response accordingly. This ability might be an important strategy in
      complex habitats such as soils, with great implications for shaping the microbial
      community structure. Here, we used a sand microcosm approach to investigate how
      Pseudomonas fluorescens Pf0-1 responds to the presence of monocultures or
      mixtures of two phylogenetically different bacteria, a Gram-negative (Pedobacter
      sp. V48) and a Gram-positive (Bacillus sp. V102) under two nutrient conditions.
      Results revealed that under both nutrient poor and nutrient rich conditions
      confrontation with the Gram-positive Bacillus sp. V102 strain led to significant
      lower cell numbers of Pseudomonas fluorescens Pf0-1, whereas confrontation with
      the Gram-negative Pedobacter sp. V48 strain did not affect the growth of
      Pseudomonas fluorescens Pf0-1. However, when Pseudomonas fluorescens Pf0-1 was
      confronted with the mixture of both strains, no significant effect on the growth
      of Pseudomonas fluorescens Pf0-1 was observed. Quantitative real-time PCR data
      showed up-regulation of genes involved in the production of a broad-spectrum
      antibiotic in Pseudomonas fluorescens Pf0-1 when confronted with Pedobacter sp.
      V48, but not in the presence of Bacillus sp. V102. The results provide evidence
      that the performance of bacteria in soil depends strongly on the identity of
      neighbouring bacteria and that inter-specific interactions are an important
      factor in determining microbial community structure. 

PMID- 25774767
TI  - Synthesis and complementary self-association of novel lipophilic pi-conjugated
      nucleoside oligomers.
AB  - A series of lipophilic nucleosides comprising natural and non-natural bases that
      are pi-conjugated to a short oligophenylene-ethynylene fragment has been
      synthesized. These bases comprise guanosine, isoguanosine, and 2-aminoadenosine
      as purine heterocycles, and cytidine, isocytosine and uridine as complementary
      pyrimidine bases. The hydrogen-bonding dimerization and association processes
      between complementary bases were also studied by (1)H NMR and absorption
      spectroscopy in order to obtain the relevant association constants. 

PMID- 25774768
TI  - A case-control study to identify risk factors associated with avian influenza
      subtype H9N2 on commercial poultry farms in Pakistan.
AB  - A 1:1 matched case-control study was conducted to identify risk factors for avian
      influenza subtype H9N2 infection on commercial poultry farms in 16 districts of
      Punjab, and 1 administrative unit of Pakistan. One hundred and thirty-three
      laboratory confirmed positive case farms were matched on the date of sample
      submission with 133 negative control farms. The association between a series of
      farm-level characteristics and the presence or absence of H9N2 was assessed by
      univariable analysis. Characteristics associated with H9N2 risk that passed the
      initial screening were included in a multivariable conditional logistic
      regression model. Manual and automated approaches were used, which produced
      similar models. Key risk factors from all approaches included selling of
      eggs/birds directly to live bird retail stalls, being near case/infected farms, a
      previous history of infectious bursal disease (IBD) on the farm and having cover
      on the water storage tanks. The findings of current study are in line with
      results of many other studies conducted in various countries to identify similar
      risk factors for AI subtype H9N2 infection. Enhancing protective measures and
      controlling risks identified in this study could reduce spread of AI subtype H9N2
      and other AI viruses between poultry farms in Pakistan. 

PMID- 25774770
TI  - Correction: Nosewitness identification: effects of negative emotion.

PMID- 25774769
TI  - Inhaled Corticosteroids for Chronic Obstructive Pulmonary Disease--The Shifting
      Treatment Paradigm.
AB  - Chronic obstructive pulmonary disease (COPD) guidelines suggest using inhaled
      corticosteroids (ICS) in patients with severe airflow limitation or those at high
      risk of exacerbations. This recommendation is based on evidence demonstrating
      that ICS, especially when prescribed in fixed-dose combinations (FDC) with long
      acting beta2 agonists (LABA), improve quality of life (QoL), decrease
      exacerbations and hospitalisations, and have been associated with a trend towards
      a reduction in all-cause mortality. Audit shows that routine prescribing practice
      frequently uses inhaler therapies outside current guidelines recommendations;
      severe to very severe disease constitutes about 20% of all COPD patients, but up
      to 75% of COPD patients are prescribed an ICS, with significant numbers given
      ICS/LABA as first-line maintenance therapy. The role of ICS in the treatment
      paradigm for COPD is changing, driven by the growing evidence of increased risk
      of pneumonia, and the introduction of a new class of FDC; LABA and long-acting
      muscarinic antagonists (LAMA), which simplify dual bronchodilation and present a
      plausible alternative therapy. As the evidence base for dual therapy
      bronchodilation expands, it is likely that maximal bronchodilation will move up
      the treatment algorithm and ICS reserved for those with more severe disease who
      are not controlled on dual therapy. This change has already manifested in local
      COPD algorithms, such as those at Tayside, and represents a significant change in
      recommended prescribing practice. This review reassesses the role of ICS in the
      shifting treatment paradigm, in the context of alternative treatment options that
      provide maximal bronchodilation.

PMID- 25774772
TI  - [Not Available].

PMID- 25774773
TI  - A stressful microenvironment: opposing effects of the endoplasmic reticulum
      stress response in the suppression and enhancement of adaptive tumor immunity.
AB  - The recent clinical success of immunotherapy in the treatment of certain types of
      cancer has demonstrated the powerful ability of the immune system to control
      tumor growth, leading to significantly improved patient survival. However,
      despite these promising results current immunotherapeutic strategies are still
      limited and have not yet achieved broad acceptance outside the context of
      metastatic melanoma. The limitations of current immunotherapeutic approaches can
      be attributed in part to suppressive mechanisms present in the tumor
      microenvironment that hamper the generation of robust antitumor immune responses
      thus allowing tumor cells to escape immune-mediated destruction. The endoplasmic
      reticulum (ER) stress response has recently emerged as a potent regulator of
      tumor immunity. The ER stress response is an adaptive mechanism that allows tumor
      cells to survive in the harsh growth conditions inherent to the tumor milieu such
      as low oxygen (hypoxia), low pH and low levels of glucose. Activation of ER
      stress can also alter the cancer cell response to therapies. In addition, the ER
      stress response promotes tumor immune evasion by inducing the production of
      protumorigenic inflammatory cytokines and impairing tumor antigen presentation.
      However, the ER stress response can boost antitumor immunity in some situations
      by enhancing the processing and presentation of tumor antigens and by inducing
      the release of immunogenic factors from stressed tumor cells. Here, we discuss
      the dualistic role of the ER stress response in the modulation of tumor immunity
      and highlight how strategies to either induce or block ER stress can be employed
      to improve the clinical efficacy of tumor immunotherapy. 

PMID- 25774771
TI  - A Review of Opioid Overdose Prevention and Naloxone Prescribing: Implications for
      Translating Community Programming Into Clinical Practice.
AB  - BACKGROUND: As physicians have increased opioid prescribing, overdose deaths from
      pharmaceutical opioids have substantially increased in the United States.
      Naloxone hydrochloride (naloxone), an opioid antagonist, is the standard of care
      for treatment of opioid induced respiratory depression. Since 1996, community
      based programs have offered overdose prevention education and distributed
      naloxone for bystander administration to people who use opioids, particularly
      heroin. There is growing interest in translating overdose education and naloxone
      distribution (OEND) into conventional medical settings for patients who are
      prescribed pharmaceutical opioids. For this review, we summarized and classified
      existing publications on overdose education and naloxone distribution to identify
      evidence of effectiveness and opportunities for translation into conventional
      medical settings. METHODS: For this review, we searched English language PubMed
      for articles on naloxone based on primary data collection from humans, including
      feasibility studies, program evaluations, surveys, qualitative studies, and
      studies comparing the effectiveness of different routes of naloxone
      administration. We also included cost-effectiveness studies. RESULTS: We
      identified 41 articles that represented 5 categories: evaluations of OEND
      programs, effects of OEND programs on experiences and attitudes of participants,
      willingness of medical providers to prescribe naloxone, comparisons of different
      routes of naloxone administration, and the cost-effectiveness of naloxone.
      CONCLUSIONS: Existing research suggests that people who are at risk for overdose
      and other bystanders are willing and able to be trained to prevent overdoses and
      administer naloxone. Counseling patients about the risks of opioid overdose and
      prescribing naloxone is an emerging clinical practice that may reduce fatalities
      from overdose while enhancing the safe prescribing of opioids.

PMID- 25774774
TI  - Plasmonics in atomically thin materials.
AB  - The observation and electrical manipulation of infrared surface plasmons in
      graphene have triggered a search for similar photonic capabilities in other
      atomically thin materials that enable electrical modulation of light at visible
      and near-infrared frequencies, as well as strong interaction with optical quantum
      emitters. Here, we present a simple analytical description of the optical
      response of such kinds of structures, which we exploit to investigate their
      application to light modulation and quantum optics. Specifically, we show that
      plasmons in one-atom-thick noble-metal layers can be used both to produce
      complete tunable optical absorption and to reach the strong-coupling regime in
      the interaction with neighboring quantum emitters. Our methods are applicable to
      any plasmon-supporting thin materials, and in particular, we provide parameters
      that allow us to readily calculate the response of silver, gold, and graphene
      islands. Besides their interest for nanoscale electro-optics, the present study
      emphasizes the great potential of these structures for the design of quantum
      nanophotonics devices. 

PMID- 25774775
TI  - Trends in animal rabies surveillance in the endemic state of Minas Gerais,
      Brazil.
AB  - Rabies is a viral zoonosis affecting mammal species and causes large economic
      losses. Included among the neglected diseases, it is still insufficiently
      addressed by governments and the international community, despite formal
      surveillance and control programs. This study used a dataset of 10,112 rabies
      diagnoses in animals provided by the Brazilian passive surveillance system from
      2001 to 2012. The positivity rate of the tested samples was 26.4%, and a
      reduction in the total samples sent during the last six years was observed. The
      kernel density map indicated case concentration in the south region and a
      decrease in density of rabies cases in the second period studied (2007 to 2012).
      The directional trend of positive rabies diagnoses remained in the south region,
      as shown by the standard deviational ellipse. The spatial scan statistic
      identified three large clusters of positive diagnoses, one in the first period
      (2001-2006) and two in the second period (2007-2012), indicating an expansion of
      risk areas. The decrease in rabies cases from 2006 to 2012 does not necessarily
      reflect lower viral circulation or improvement in actions by epidemiological
      surveillance; this decrease could indicate a deficiency in epidemiological
      surveillance during the observation period due to the increase in the silent
      areas. Surveillance should maintain an increasing or constant number of tests
      during the years in addition to a reduction in the number of outbreaks of rabies,
      which would indicate a lower positivity rate. The findings in this study indicate
      deterioration in the effectiveness of the passive surveillance for rabies. The
      number of rabies cases, total number of tests performed and positivity rate are
      good indicators for evaluating passive surveillance. This paper can function as a
      guide for the assessment and improvement of the actions in passive surveillance
      of rabies. 

PMID- 25774776
TI  - Warming and nitrogen addition increase litter decomposition in a temperate meadow
      ecosystem.
AB  - BACKGROUND: Litter decomposition greatly influences soil structure, nutrient
      content and carbon sequestration, but how litter decomposition is affected by
      climate change is still not well understood. METHODOLOGY/PRINCIPAL FINDINGS: A
      field experiment with increased temperature and nitrogen (N) addition was
      established in April 2007 to examine the effects of experimental warming, N
      addition and their interaction on litter decomposition in a temperate meadow
      steppe in northeastern China. Warming, N addition and warming plus N addition
      reduced the residual mass of L. chinensis litter by 3.78%, 7.51% and 4.53%,
      respectively, in 2008 and 2009, and by 4.73%, 24.08% and 16.1%, respectively, in
      2010. Warming, N addition and warming plus N addition had no effect on the
      decomposition of P. communis litter in 2008 or 2009, but reduced the residual
      litter mass by 5.58%, 15.53% and 5.17%, respectively, in 2010. Warming and N
      addition reduced the cellulose percentage of L. chinensis and P. communis,
      specifically in 2010. The lignin percentage of L. chinensis and P. communis was
      reduced by warming but increased by N addition. The C, N and P contents of L.
      chinensis and P. communis litter increased with time. Warming and N addition
      reduced the C content and C:N ratios of L. chinensis and P. communis litter, but
      increased the N and P contents. Significant interactive effects of warming and N
      addition on litter decomposition were observed (P<0.01). CONCLUSION/SIGNIFICANCE:
      The litter decomposition rate was highly correlated with soil temperature, soil
      water content and litter quality. Warming and N addition significantly impacted
      the litter decomposition rate in the Songnen meadow ecosystem, and the effects of
      warming and N addition on litter decomposition were also influenced by the
      quality of litter. These results highlight how climate change could alter
      grassland ecosystem carbon, nitrogen and phosphorus contents in soil by
      influencing litter decomposition.

PMID- 25774778
TI  - Correction: High fat diet subverts hepatocellular iron uptake determining
      dysmetabolic iron overload.

PMID- 25774779
TI  - Validation of the Curiosity and Exploration Inventory-II (CEI-II) Among Chinese
      University Students in Hong Kong.
AB  - This study aimed at validating the Curiosity and Exploration Inventory-II (CEI
      II; Kashdan et al., 2009 ) in a Chinese context. A total of 294 Chinese first
      year undergraduate students in Hong Kong completed the CEI-II and measures of
      satisfaction with university life, the Big Five personality traits, and human
      values. The results of exploratory structural equation modeling, parallel
      analysis, and confirmatory factor analysis supported a 1-factor solution and did
      not replicate the original 2-factor structure. Time invariance of the 1-factor
      structure was obtained among 242 participants who completed the questionnaires
      again after 4 months. The latent means and correlation indicated that curiosity
      as measured by the CEI-II was quite stable over the period of investigation. The
      CEI-II was found to be positively correlated with satisfaction with university
      life, extraversion, agreeableness, conscientiousness, openness to experience, and
      openness to change values, but negatively with neuroticism and conservation
      values. The results of hierarchical multiple regression analyses showed that the
      CEI-II score had incremental validity above and beyond the Big Five personality
      traits in predicting human values and satisfaction with university life. 

PMID- 25774777
TI  - The long pentraxin PTX3 promotes fibrocyte differentiation.
AB  - Monocyte-derived, fibroblast-like cells called fibrocytes are associated with
      fibrotic lesions. The plasma protein serum amyloid P component (SAP; also known
      as pentraxin-2, PTX2) inhibits fibrocyte differentiation in vitro, and injections
      of SAP inhibit fibrosis in vivo. SAP is a member of the pentraxin family of
      proteins that includes C-reactive protein (CRP; PTX1) and pentraxin-3 (PTX3). All
      three pentraxins are associated with fibrosis, but only SAP and CRP have been
      studied for their effects on fibrocyte differentiation. We find that compared to
      SAP and CRP, PTX3 promotes human and murine fibrocyte differentiation. The effect
      of PTX3 is dependent on FcgammaRI. In competition studies, the fibrocyte
      inhibitory activity of SAP is dominant over PTX3. Binding competition studies
      indicate that SAP and PTX3 bind human FcgammaRI at different sites. In murine
      models of lung fibrosis, PTX3 is present in fibrotic areas, and the PTX3
      distribution is associated with collagen deposition. In lung tissue from
      pulmonary fibrosis patients, PTX3 has a widespread distribution, both in
      unaffected tissue and in fibrotic lesions, whereas SAP is restricted to areas
      adjacent to vessels, and absent from fibrotic areas. These data suggest that the
      relative levels of SAP and PTX3 present at sites of fibrosis may have a
      significant effect on the ability of monocytes to differentiate into fibrocytes. 

PMID- 25774781
TI  - Validation of a novel shotgun proteomic workflow for the discovery of protein
      protein interactions: focus on ZNF521.
AB  - The study of protein-protein interactions is increasingly relying on mass
      spectrometry (MS). The classical approach of separating immunoprecipitated
      proteins by SDS-PAGE followed by in-gel digestion is long and labor-intensive.
      Besides, it is difficult to integrate it with most quantitative MS-based
      workflows, except for stable isotopic labeling of amino acids in cell culture
      (SILAC). This work describes a fast, flexible and quantitative workflow for the
      discovery of novel protein-protein interactions. A cleavable cross-linker,
      dithiobis[succinimidyl propionate] (DSP), is utilized to stabilize protein
      complexes before immunoprecipitation. Protein complex detachment from the
      antibody is achieved by limited proteolysis. Finally, protein quantitation is
      performed via (18)O labeling. The workflow has been optimized concerning (i) DSP
      concentration and (ii) incubation times for limited proteolysis, using the stem
      cell-associated transcription cofactor ZNF521 as a model target. The interaction
      of ZNF521 with the core components of the nuclear remodelling and histone
      deacetylase (NuRD) complex, already reported in the literature, was confirmed.
      Additionally, interactions with newly discovered molecular partners of
      potentially relevant functional role, such as ZNF423, Spt16, Spt5, were
      discovered and validated by Western blotting. 

PMID- 25774780
TI  - High-fat feeding impairs nutrient sensing and gut brain integration in the
      caudomedial nucleus of the solitary tract in mice.
AB  - Hyperphagic obesity is characterized in part by a specific increase in meal size
      that contributes to increased daily energy intake, but the mechanisms underlying
      impaired activity of meal size regulatory circuits, particularly those converging
      at the caudomedial nucleus of the solitary tract in the hindbrain (cmNTS), remain
      poorly understood. In this paper, we assessed the consequences of high-fat (HF)
      feeding and diet-induced obesity (DIO) on cmNTS nutrient sensing and metabolic
      integration in the control of meal size. Mice maintained on a standard chow diet,
      low-fat (LF) diet or HF diet for 2 weeks or 6 months were implanted with a
      bilateral brain cannula targeting the cmNTS. Feeding behavior was assessed using
      behavioral chambers and meal-pattern analysis following cmNTS L-leucine
      injections alone or together with ip CCK. Molecular mechanisms implicated in the
      feeding responses were assessed using western blot, immunofluorescence and
      pharmacological inhibition of the amino acid sensing mTORC1 pathway (mammalian
      target of rapamycin complex 1). We found that HF feeding blunts the anorectic
      consequences of cmNTS L-leucine administration. Increased baseline activity of
      the L-leucine sensor P70 S6 kinase 1 and impaired L-leucine-induced activation of
      this pathway in the cmNTS of HF-fed mice indicate that HF feeding is associated
      with an impairment in cmNTS mTOR nutritional and hormonal sensing. Interestingly,
      the acute orexigenic effect of the mTORC1 inhibitor rapamycin was preserved in HF
      fed mice, supporting the assertion that HF-induced increase in baseline cmNTS
      mTORC1 activity underlies the defect in L-leucine sensing. Last, the synergistic
      feeding-suppressive effect of CCK and cmNTS L-leucine was abrogated in DIO mice.
      These results indicate that HF feeding leads to an impairment in cmNTS nutrient
      sensing and metabolic integration in the regulation of meal size. 

PMID- 25774782
TI  - "Read My Lips"--Empty Words: The Semantics of Institutionalized Flawing.

PMID- 25774784
TI  - A Physiologist's War: Captain T. Graham Brown RAMC (1915-1919).
AB  - During the five years before the outbreak of the First World War, Thomas Graham
      Brown (1882-1965) conducted research into the control of locomotion that gained
      him a deserved and long-lasting reputation as a neuroscientist and, in 1927, was
      recognized by election to the Fellowship of the Royal Society. In 1915, with the
      First World War raging, he agonized about continuing his research or joining the
      Royal Army Medical Corps (RAMC). Told by his father to seek a commission, he
      served two and half years in Macedonia with the British Salonika Force. Whilst in
      Greece, he kept a daily diary. The entries from June 1916 to May 1917 are extant.
      They are unpublished and provide the background to the narrative to follow.
      Casualties with traumatic injury to the brain and spinal cord afforded him the
      opportunity to carry out careful observations, particularly concerning sensory
      localization, which resulted in novel findings and his observations on shell
      shock led to him being called as an expert witness to the national inquiry into
      the nature and treatment of the condition. In 1920, Graham Brown was appointed to
      the Chair of Physiology in Cardiff, which he held until 1947. 

PMID- 25774785
TI  - Predicting suicide attempts by time-varying frequency of nonsuicidal self-injury
      among Chinese community adolescents.
AB  - OBJECTIVE: This study predicted suicide attempts (SA) by time-varying frequency
      of nonsuicidal self-injury (NSSI) beyond the contributions of their shared risk
      factors and examined gender differences in this association. This study also
      tested for a moderating effect of NSSI in the relationship between suicide
      ideation (SI) and SA. METHOD: A large number of Chinese adolescents participated
      in this study (the exact number of participants varied from 3,623 to 6,911 in
      different analyses). They completed questionnaires assessing NSSI, SA, SI,
      borderline personality disorder features, depressive symptoms, and self-criticism
      3 times at 6-month intervals. Generalized estimating equations were used to test
      the hypotheses. RESULTS: In females, but not in males, NSSI was significantly
      associated with future SA after controlling for the effects of shared risk
      factors. With the same frequency of SI, the frequency of NSSI also enhanced the
      risk for future SA. CONCLUSIONS: This study established a longitudinal
      association between NSSI and SA, which could not be fully accounted for by their
      shared risk factors, in Chinese female community adolescents. Moreover, female
      adolescents who frequently engage in NSSI may gain the capability for attempting
      suicide.

PMID- 25774783
TI  - S-adenosyl-L-methionine for the treatment of chronic liver disease: a systematic
      review and meta-analysis.
AB  - It has been well established that S-adenosyl-L-methionine (SAMe) is the principal
      methyl donor in methyltransferase reactions and that SAMe supplementation
      restores hepatic glutathione (GSH) deposits and attenuates liver injury. However,
      the effectiveness of SAMe therapy in chronic liver disease has not been
      adequately addressed. We searched globally recognized electronic databases,
      including PubMed, the Cochrane Database and EMBASE, to retrieve relevant
      randomized controlled trials (RCTs) of chronic liver disease published in the
      past 20 years. We then performed a systematic review and meta-analysis of the
      enrolled trials that met the inclusion criteria.The results showed that twelve
      RCTs from 11 studies, which examined 705 patients, were included in this
      research. For liver function, certain results obtained from data synthesis and
      independent comparisons demonstrated significant differences between the levels
      of total bilirubin (TBIL) and aspartate transaminase (AST). However, no studies
      identified significant differences regarding alanine transaminase (ALT) levels.
      An analysis of the adverse events and long-term prognosis also indicated no
      significant differences between the SAMe and the placebo groups. In a subgroup
      analysis of gravidas and children, several of the included data indicated that
      there was a significant difference in the pruritus score. Furthermore, the
      results regarding ursodeoxycholic acid (UDCA) and stronger neo-minophagen C
      (SNMC) indicated that both treatments were more effective than SAMe was in
      certain chronic liver diseases. These findings suggest that SAMe could be used as
      the basis of a medication regimen for liver function improvement because of its
      safety. However, SAMe also demonstrated limited clinical value in the treatment
      of certain chronic liver diseases. 

PMID- 25774786
TI  - Diagnoses, intervention strategies, and rates of functional improvement in
      integrated behavioral health care patients.
AB  - OBJECTIVE: Compared with more traditional mental health care, integrated
      behavioral health care (IBHC) offers greater access to services and earlier
      identification and intervention of behavioral and mental health difficulties. The
      current study examined demographic, diagnostic, and intervention factors that
      predict positive changes for IBHC patients. METHOD: Participants were 1,150
      consecutive patients (mean age = 30.10 years, 66.6% female, 60.1% Hispanic, 47.9%
      uninsured) seen for IBHC services at 2 primary care clinics over a 34-month
      period. Patients presented with depressive (23.2%), anxiety (18.6%), adjustment
      (11.3%), and childhood externalizing (7.6%) disorders, with 25.7% of patients
      receiving no diagnosis. RESULTS: The most commonly delivered interventions
      included behavioral activation (26.1%), behavioral medicine-specific consultation
      (14.6%), relaxation training (10.3%), and parent-management training (8.5%).
      There was high concordance between diagnoses and evidence-based intervention
      selection. We used latent growth curve modeling to explore predictors of baseline
      global assessment of functioning (GAF) and improvements in GAF across sessions,
      utilizing data from a subset of 117 patients who attended at least 3 behavioral
      health visits. Hispanic ethnicity and being insured predicted higher baseline
      GAF, while patients with an anxiety disorder had lower baseline GAF than patients
      with other diagnoses. Controlling for primary diagnosis, patients receiving
      behavioral activation or exposure therapy improved at faster rates than patients
      receiving other interventions. Demographic variables did not relate to rates of
      improvement. CONCLUSION: Results suggest even brief IBHC interventions can be
      focused, targeting specific patient concerns with evidence-based treatment
      components. (PsycINFO Database Record

PMID- 25774787
TI  - Antibodies to inhibitory synaptic proteins in neurological syndromes associated
      with glutamic acid decarboxylase autoimmunity.
AB  - Antibodies to glutamic acid decarboxylase (GAD-ab) associate to different
      neurological syndromes. It is unknown if the diversity in syndrome association
      represents epitopes in different immunodominant domains or co-existence of
      antibodies to other proteins of the inhibitory synapsis. We examined the serum
      and CSF of 106 patients with anti-GAD related syndromes (39 cerebellar ataxia, 32
      stiff-person syndrome [SPS], 18 epilepsy, and 17 limbic encephalitis [LE]). GAD65
      ab titres were quantified by ELISA. Immunoblot was used to determine if the
      antibody-targeted epitopes of GAD65 and GAD67 were linear. A cell-based assay
      (CBA) with HEK293 cells expressing the GAD65 N-terminal, central catalytic
      domain, or C-terminal was used to investigate the immunodominant domains.
      Antibodies to GAD67, gamma-aminobutyric acid A receptor (GABAaR), glycine
      receptor (GlyR), GABAaR-associated protein (GABARAP), and gephyrin were
      determined with CBA. GAD-ab internalization was investigated using cultured rat
      hippocampal neurons. CSF GAD65-ab titres were higher in patients with cerebellar
      ataxia and LE compared to those with SPS (p = 0.02). GAD67-ab were identified in
      81% of sera and 100% of CSF. GAD65-ab recognized linear epitopes in 98% of the
      patients and GAD67-ab in 42% (p<0.001). The GAD65 catalytic domain was recognized
      by 93% of sera, and the three domains by 22% of sera and 74% of CSF (p<0.001).
      Six patients had GABAaR-ab and another 6 had GlyR-ab without association to
      distinctive symptoms. None of the patients had gephyrin- or GABARAP-ab. GAD65-ab
      were not internalized by live neurons. Overall, these findings show that
      regardless of the neurological syndrome, the CSF immune response against GAD is
      more widespread than that of the serum and that there is no specific association
      between clinical phenotype and the presence of antibodies against other proteins
      of the inhibitory synapsis. 

PMID- 25774789
TI  - Interactions of the acyl chain with the Saccharomyces cerevisiae acyl carrier
      protein.
AB  - Acyl carrier protein (ACP) domains are critical integral components of
      multifunctional type I fatty acid synthases (FAS I) and polyketide synthases
      (PKSs), where they shuttle the growing adducts of the synthesis between the
      catalytic domains. In contrast to ACP of mammalian FAS I, PKSs, and the
      dissociated fatty acid synthase type II systems (FAS II) of bacteria, fungal FAS
      I ACP consists of two subdomains, one comprising the canonical ACP fold observed
      in all FAS systems and the other representing an extra structural subdomain.
      While ACPs of dissociated FAS II are able to sequester the reaction intermediates
      during substrate shuttling, such a transport mechanism has not been observed in
      ACP domains of multifunctional FAS I and PKS systems. For a better understanding
      of the interaction between the canonical subdomain of fungal ACP with the growing
      acyl chain and the role of the structural subdomain, we determined the structure
      of the isolated Saccharomyces cerevisiae acyl carrier protein (ScACP) domain by
      NMR spectroscopy and investigated the interactions between ScACP and covalently
      attached substrate acyl chains of varying length by monitoring chemical shift
      perturbations. The interactions were mapped to the hydrophobic core of the
      canonical subdomain, while no perturbations were detected in the structural
      subdomain. A population analysis revealed that only approximately 15% of
      covalently attached decanoyl chains are sequestered by the ACP core, comparable
      to the mammalian FAS I and multifunctional PKS systems, which do not sequester
      their substrates. Finally, denaturation experiments show that both ScACP
      subdomains unfold cooperatively and that the weak interaction of the acyl chain
      with the hydrophobic core does not significantly affect the ACP stability. 

PMID- 25774788
TI  - Remission of collagen-induced arthritis through combination therapy of
      microfracture and transplantation of thermogel-encapsulated bone marrow
      mesenchymal stem cells.
AB  - The persistent inflammation of rheumatoid arthritis (RA) always leads to partial
      synovial hyperplasia and the destruction of articular cartilage. Bone marrow
      mesenchymal stem cells (BMMSCs) have been proven to possess immunosuppressive
      effects, and widely explored in the treatment of autoimmune diseases. However,
      poor inhibitory effect on local inflammatory state and limited capacity of
      preventing destruction of articular cartilage by systemic BMMSCs transplantation
      were observed. Herein, toward the classical type II collagen-induced arthritis in
      rats, the combination treatment of microfracture and in situ transplantation of
      thermogel-encapsulated BMMSCs was verified to obviously down-regulate the ratio
      of CD4+ to CD8+ T lymphocytes in peripheral blood. In addition, it resulted in
      the decreased levels of inflammatory cytokines, such as interleukin-1beta, tumor
      necrosis factor-alpha and anti-collagen type II antibody, in the serum.
      Simultaneously, the combination therapy also could inhibit the proliferation of
      antigen specific lymphocytes and local joint inflammatory condition, and prevent
      the articular cartilage damage. The results indicated that the treatment programs
      could effectively stimulate the endogenous and exogenous BMMSCs to exhibit the
      immunosuppression and cartilage protection capability. This study provided a new
      therapeutic strategy for autoimmune inflammatory diseases, such as RA. 

PMID- 25774790
TI  - Mechanism of intersystem crossing of thermally activated delayed fluorescence
      molecules.
AB  - The spin sublevel dynamics of the excited triplet state in thermally activated
      delayed fluorescence (TADF) molecules have not been investigated for high
      intensity organic light-emitting diode materials. Understanding the mechanism for
      intersystem crossing (ISC) is thus important for designing novel TADF materials.
      We report the first study on the ISC dynamics of the lowest excited triplet state
      from the lowest excited singlet state with charge-transfer (CT) character of TADF
      molecules with different external quantum efficiencies (EQEs) using time-resolved
      electron paramagnetic resonance methods. Analysis of the observed spin
      polarization indicates a strong correlation of the EQE with the population rate
      due to ISC induced by hyperfine coupling with the magnetic nuclei. It is
      concluded that molecules with high EQE have an extremely small energy gap between
      the (1)CT and (3)CT states, which allows an additional ISC channel due to the
      hyperfine interactions. 

PMID- 25774791
TI  - Increased risk of cutaneous melanoma associated with p53 Arg72Pro polymorphism.
AB  - OBJECTIVE: The objective of this study was to test the hypothesis that p53
      Arg72Pro polymorphism may contribute to an increased risk of cutaneous melanoma
      (CM). METHODS: By searching the databases of PubMed, EMBASE, and Web of Science,
      a total of 8 eligible case-control studies with 1,957 CM cases and 2,887 controls
      were included in this meta-analysis. Stata software was used to analyze all the
      statistical data. RESULTS: The pooled data by a fixed-effects model suggested an
      increased risk of CM associated with p53 Arg72Pro polymorphism under the genetic
      model of Arg/Pro vs. Pro/Pro without heterogeneity (ORArg/Pro vs. Pro/Pro = 1.76,
      95% CI = 1.55-1.99, Pheterogeneity = 0.075). A similar trend was seen in
      subgroups of hospital-based studies and population-based studies. CONCLUSION: Our
      meta-analysis based on all studies shows that the p53 Arg72Pro polymorphism may
      increase individual susceptibility to CM, particularly in Caucasians and could
      serve as a biomarker to predict the population at high risk of CM.

PMID- 25774792
TI  - Continual cell deformation induced via attachment to oriented fibers enhances
      fibroblast cell migration.
AB  - Fibroblast migration is critical to the wound healing process. In vivo, migration
      occurs on fibrillar substrates, and previous observations have shown that a
      significant time lag exists before the onset of granulation tissue. We therefore
      conducted a series of experiments to understand the impact of both fibrillar
      morphology and migration time. Substrate topography was first shown to have a
      profound influence. Fibroblasts preferentially attach to fibrillar surfaces, and
      orient their cytoplasm for maximal contact with the fiber edge. In the case of en
      mass cell migration out of an agarose droplet, fibroblasts on flat surfaces
      emerged with an enhanced velocity, v = 52MUm/h, that decreases to the single cell
      value, v = 28MUm/h within 24 hours and remained constant for at least four days.
      Fibroblasts emerging on fibrillar surfaces emerged with the single cell velocity,
      which remained constant for the first 24 hours and then increased reaching a
      plateau with more than twice the initial velocity within the next three days. The
      focal adhesions were distributed uniformly in cells on flat surfaces, while on
      the fibrillar surface they were clustered along the cell periphery. Furthermore,
      the number of focal adhesions for the cells on the flat surfaces remained
      constant, while it decreased on the fibrillar surface during the next three days.
      The deformation of the cell nuclei was found to be 50% larger on the fiber
      surfaces for the first 24 hours. While the mean deformation remained constant on
      the flat surface, it increased for the next three days by 24% in cells on fibers.
      On the fourth day, large actin/myosin fibers formed in cells on fibrillar
      surfaces only and coincided with a change from the standard migration mechanism
      involving extension of lamellipodia, and retraction of the rear, to one involving
      strong contractions oriented along the fibers and centered about the nucleus. 

PMID- 25774793
TI  - Molecular phylogenetic analysis of non-sexually transmitted strains of
      Haemophilus ducreyi.
AB  - Haemophilus ducreyi, the etiologic agent of chancroid, has been previously
      reported to show genetic variance in several key virulence factors, placing
      strains of the bacterium into two genetically distinct classes. Recent studies
      done in yaws-endemic areas of the South Pacific have shown that H. ducreyi is
      also a major cause of cutaneous limb ulcers (CLU) that are not sexually
      transmitted. To genetically assess CLU strains relative to the previously
      described class I, class II phylogenetic hierarchy, we examined nucleotide
      sequence diversity at 11 H. ducreyi loci, including virulence and housekeeping
      genes, which encompass approximately 1% of the H. ducreyi genome. Sequences for
      all 11 loci indicated that strains collected from leg ulcers exhibit DNA
      sequences homologous to class I strains of H. ducreyi. However, sequences for 3
      loci, including a hemoglobin receptor (hgbA), serum resistance protein (dsrA),
      and a collagen adhesin (ncaA) contained informative amounts of variation.
      Phylogenetic analyses suggest that these non-sexually transmitted strains of H.
      ducreyi comprise a sub-clonal population within class I strains of H. ducreyi.
      Molecular dating suggests that CLU strains are the most recently developed,
      having diverged approximately 0.355 million years ago, fourteen times more
      recently than the class I/class II divergence. The CLU strains' divergence falls
      after the divergence of humans from chimpanzees, making it the first known H.
      ducreyi divergence event directly influenced by the selective pressures
      accompanying human hosts. 

PMID- 25774794
TI  - Modifying effects of vitamin E on chlorpyrifos toxicity in atlantic salmon.
AB  - The aim of this study was to elucidate how vitamin E (alpha tocopherol) may
      ameliorate the toxicity of the pesticide chlorpyrifos in Atlantic salmon. Freshly
      isolated hepatocytes were exposed to vitamin E, chlorpyrifos or a combination of
      vitamin E and chlorpyrifos (all 100 MUM). Transcriptomics (RNA-seq) and
      metabolomics were used to screen for effects of vitamin E and chlorpyrifos. By
      introducing vitamin E, the number of upregulated transcripts induced by
      chlorpyrifos exposure was reduced from 941 to 626, while the number of
      downregulated transcripts was reduced from 901 to 742 compared to the control.
      Adding only vitamin E had no effect on the transcriptome. Jak-STAT signaling was
      the most significantly affected pathway by chlorpyrifos treatment according to
      the transcriptomics data. The metabolomics data showed that accumulation of
      multiple long chain fatty acids and dipeptides and amino acids in chlorpyrifos
      treated cells was partially alleviated by vitamin E treatment. Significant
      interaction effects between chlorpyrifos and vitamin E were seen for 15
      metabolites, including 12 dipeptides. The antioxidant had relatively modest
      effects on chlorpyrifos-induced oxidative stress. By combining the two data sets,
      the study suggests that vitamin E supplementation prevents uptake and
      accumulation of fatty acids, and counteracts inhibited carbohydrate metabolism.
      Overall, this study shows that vitamin E only to a moderate degree modifies
      chlorpyrifos toxicity in Atlantic salmon liver cells. 

PMID- 25774795
TI  - Molecular taxonomy provides new insights into anopheles species of the
      neotropical arribalzagia series.
AB  - Phylogenetic analysis of partial mitochondrial cytochrome oxidase c subunit I
      (COI) and nuclear internal transcribed spacer 2 (ITS2) sequences were used to
      evaluate initial identification and to investigate phylogenetic relationships of
      seven Anopheles morphospecies of the Arribalzagia Series from Colombia.
      Phylogenetic trees recovered highly supported clades for An. punctimaculas.s.,
      An. calderoni, An. malefactor s.l., An. neomaculipalpus, An. apicimacula s.l.,
      An. mattogrossensis and An. peryassui. This study provides the first molecular
      confirmation of An. malefactorfrom Colombia and discovered conflicting patterns
      of divergence for the molecular markers among specimens from northeast and
      northern Colombia suggesting the presence of two previously unrecognized
      Molecular Operational Taxonomic Units (MOTUs). Furthermore, two highly
      differentiated An. apicimacula MOTUs previously found in Panama were detected.
      Overall, the combined molecular dataset facilitated the detection of known and
      new Colombian evolutionary lineages, and constitutes the baseline for future
      research on their bionomics, ecology and potential role as malaria vectors. 

PMID- 25774796
TI  - Possible role of minor h antigens in the persistence of donor chimerism after
      stem cell transplantation; relevance for sustained leukemia remission.
AB  - Persistent complete donor chimerism is an important clinical indicator for
      remissions of hematological malignancies after HLA-matched allogeneic stem cell
      transplantation (SCT). However, the mechanisms mediating the persistence of
      complete donor chimerism are poorly understood. The frequent coincidence of
      complete donor chimerism with graft-versus-leukemia effects and graft-versus-host
      disease suggests that immune responses against minor histocompatibility antigens
      (mHags) are playing an important role in suppressing the host hematopoiesis after
      allogeneic SCT. Here, we investigated a possible relationship between donor
      immune responses against the hematopoiesis-restricted mHag HA-1 and the long-term
      kinetics of host hematopoietic chimerism in a cohort of 10 patients after
      allogeneic HLA-matched, HA-1 mismatched SCT. Functional HA-1 specific CTLs (HA-1
      CTLs) were detectable in 6/10 patients lysing host-type hematopoietic cells in
      vitro. Presence of HA-1 CTLs in the peripheral blood coincided with low host
      hematopoiesis levels quantified by highly sensitive mHag specific PCR.
      Additionally, co-incubation of host type CD34+ cells with HA-1 CTLs isolated
      after allogeneic SCT prevented progenitor and cobblestone area forming cell
      growth in vitro and human hematopoietic engraftment in immunodeficient mice.
      Conversely, absence or loss of HA-1 CTLs mostly coincided with high host
      hematopoiesis levels and/or relapse. In summary, in this first study, presence of
      HA-1 CTLs paralleled low host hematopoiesis levels. This coincidence might be
      supported by the capacity of HA-1 CTLs isolated after allogeneic SCT to
      specifically eliminate host type hematopoietic stem/progenitor cells. Additional
      studies involving multiple mismatched mHags in more patients are required to
      confirm this novel characteristic of mHag CTLs as factor for the persistence of
      complete donor chimerism and leukemia remission after allogeneic SCT. 

PMID- 25774798
TI  - Computational modelling of the antischistosomal activity for neolignan
      derivatives based on the MIA-SAR approach.
AB  - Theoretical models for exploring the antischistosomal activity of a dataset of 18
      synthetic neolignans are built using the multivariate image analysis applied to
      structure-activity relationships (MIA-SAR) approach. The obtained models were
      validated using the accuracy (Acc) in leave-one-out cross-validation, external
      validation and Y-randomization procedures, yielding correct classification
      superior to 80%, 70% and 60%, respectively. Additionally, a comparison was made
      of the models obtained from binary (black and white) and coloured images; the
      colours (pixel values) were selected to correspond to chemical properties. It was
      observed that the models obtained from coloured images with pixel values
      corresponding to electronegativity (known as the aug-MIA-SAR(colour) approach)
      generally yielded superior statistical parameters compared with those obtained
      from binary images (MIA-SAR) and randomly coloured images (atoms are coloured
      according to their type) with atomic sizes corresponding to Van der Waals radius
      (aug-MIA-SAR), respectively. Mechanistic interpretation of the influence of
      different substituents on the antischistosomal activity revealed that methoxy
      substituents in the R1 (or R2) and R5 positions of the neolignan scaffold are
      indispensable for the antischistosomal activity. The obtained results provide
      knowledge of the possible structural modifications to yield novel neolignan
      compounds with antischistosomal activity.

PMID- 25774797
TI  - Body mass index is associated with physical performance in suburb-dwelling older
      chinese: a cross-sectional study.
AB  - BACKGROUND: Physical performance is reported to have various beneficial effects
      on human health, especially in older individuals. Although such effects are
      associated with body mass index (BMI), the relationship between BMI and physical
      performance has not been clarified. DESIGN: We conducted a cross-sectional study
      of 966 suburb-dwelling Tianjin individuals aged >= 60 years (average age 67.5+/
      6.02, men 435, women 531). Mobility, balance, and muscle strength were assessed
      by walking speed, timed up-and-go test (TUGT), and grip strength, respectively.
      The subjects were categorized into three groups based on BMI (kg/m2) as follows:
      normal weight, 18.5 <= BMI <= 23.9; overweight, 24.0 <= BMI <= 27.9; and obese,
      BMI >= 28.0. RESULT: After adjusting for all other variables, relative grip
      strength decreased when BMI increased in both men and women (P for trend <0.001
      and <0.001, respectively). BMI may be negatively associated with TUGT performance
      in the women only. There was no apparent association between walking speed and
      BMI in either sex, but after adjusting for age, walking speed was faster when BMI
      increased in women (P for trend= 0.0162). CONCLUSION: This study suggests that in
      older individuals, higher BMI is associated with poor muscle strength in both
      sexes.

PMID- 25774799
TI  - Tunable solar-heat shielding property of transparent films based on mesoporous Sb
      doped SnO2 microspheres.
AB  - In this paper, mesoporous antimony doped tin oxide (ATO) microspheres are
      synthesized via a solvothermal method from a methanol system with the surfactant
      followed by a thermal treatment process. Morphology studies reveal that the
      spherical products obtained by polyvinylpyrrolidone (PVP) templating result in a
      higher uniformity in size. Such obtained ATO microspheres with a secondary
      particle size ranging between 200 and 800 nm consist of packed tiny nanocrystals
      and have high specific surface area (~98 m(2) g(-1)). The effect of Sb doping on
      the structural and electrical properties of SnO2 microspheres is studied. Because
      of the substitution of Sn(4+) with Sb(5+) accompanied by forming a shallow donor
      level close to the conduction band of SnO2, a lower resistivity of powder pellet
      can be achieved, which corresponds to the spectrally selective property of films.
      The application of ATO microspheres provides an example of transparent coatings;
      depending on Sb concentration in SnO2 and solid content of coatings, transparent
      films with tunable solar-heat shielding property are obtained. 

PMID- 25774800
TI  - First record of black band disease in the Hawaiian archipelago: response,
      outbreak status, virulence, and a method of treatment.
AB  - A high number of coral colonies, Montipora spp., with progressive tissue loss
      were reported from the north shore of Kaua'i by a member of the Eyes of the Reef
      volunteer reporting network. The disease has a distinct lesion (semi-circular
      pattern of tissue loss with an adjacent dark band) that was first observed in
      Hanalei Bay, Kaua'i in 2004. The disease, initially termed Montipora banded
      tissue loss, appeared grossly similar to black band disease (BBD), which affects
      corals worldwide. Following the initial report, a rapid response was initiated as
      outlined in Hawai'i's rapid response contingency plan to determine outbreak
      status and investigate the disease. Our study identified the three dominant
      bacterial constituents indicative of BBD (filamentous cyanobacteria, sulfate
      reducing bacteria, sulfide-oxidizing bacteria) in coral disease lesions from
      Kaua'i, which provided the first evidence of BBD in the Hawaiian archipelago. A
      rapid survey at the alleged outbreak site found disease to affect 6-7% of the
      montiporids, which is higher than a prior prevalence of less than 1% measured on
      Kaua'i in 2004, indicative of an epizootic. Tagged colonies with BBD had an
      average rate of tissue loss of 5.7 cm2/day over a two-month period. Treatment of
      diseased colonies with a double band of marine epoxy, mixed with chlorine powder,
      effectively reduced colony mortality. Within two months, treated colonies lost an
      average of 30% less tissue compared to untreated controls. 

PMID- 25774801
TI  - Chronic treatment with atrial natriuretic peptide in spontaneously hypertensive
      rats: beneficial renal effects and sex differences.
AB  - OBJECTIVE: The aim of this study was to investigate the effects of chronic
      treatment with atrial natriuretic peptide (ANP) on renal function, nitric oxide
      (NO) system, oxidative stress, collagen content and apoptosis in kidneys of
      spontaneously hypertensive rats (SHR), as well as sex-related differences in the
      response to the treatment. METHODS: 10 week-old male and female SHR were infused
      with ANP (100 ng/h/rat) or saline (NaCl 0.9%) for 14 days (subcutaneous osmotic
      pumps). Systolic blood pressure (SBP) was recorded and diuresis and natriuresis
      were determined. After treatment, renal NO synthase (NOS) activity and eNOS
      expression were evaluated. Thiobarbituric acid-reactive substances (TBARS),
      glutathione concentration and glutathione peroxidase (GPx) and superoxide
      dismutase (SOD) activities were determined in the kidney. Collagen was identified
      in renal slices by Sirius red staining and apoptosis by Tunel assay. RESULTS:
      Female SHR showed lower SBP, oxidative stress, collagen content and apoptosis in
      kidney, and higher renal NOS activity and eNOS protein content, than males. ANP
      lowered SBP, increased diuresis, natriuresis, renal NOS activity and eNOS
      expression in both sexes. Renal response to ANP was more marked in females than
      in males. In kidney, ANP reduced TBARS, renal collagen content and apoptosis, and
      increased glutathione concentration and activity of GPx and SOD enzymes in both
      sexes. CONCLUSIONS: Female SHR exhibited less organ damage than males. Chronic
      ANP treatment would ameliorate hypertension and end-organ damage in the kidney by
      reducing oxidative stress, increasing NO-system activity, and diminishing
      collagen content and apoptosis, in both sexes.

PMID- 25774802
TI  - The flavoproteins CryD and VvdA cooperate with the white collar protein WcoA in
      the control of photocarotenogenesis in Fusarium fujikuroi.
AB  - Light stimulates carotenoid biosynthesis in the ascomycete fungus Fusarium
      fujikuroi through transcriptional activation of the structural genes of the
      pathway carRA, carB, and cart, but the molecular basis of this photoresponse is
      unknown. The F. fujikuroi genome contains genes for different predicted
      photoreceptors, including the WC protein WcoA, the DASH cryptochrome CryD and the
      Vivid-like flavoprotein VvdA. We formerly found that null mutants of wcoA, cryD
      or vvdA exhibit carotenoid photoinduction under continuous illumination. Here we
      show that the wild type exhibits a biphasic response in light induction kinetics
      experiments, with a rapid increase in carotenoid content in the first hours, a
      transient arrest and a subsequent slower increase. The mutants of the three
      photoreceptors show different kinetic responses: the wcoA mutants are defective
      in the rapid response, the cryD mutants are affected in the slower response,
      while the fast and slow responses were respectively enhanced and attenuated in
      the vvdA mutants. Transcriptional analyses of the car genes revealed a strong
      reduction of dark and light-induced transcript levels in the wcoA mutants, while
      minor or no reductions were found in the cryD mutants. Formerly, we found no
      change on carRA and carB photoinduction in vvdA mutants. Taken together, our data
      suggest a cooperative participation of WcoA and CryD in early and late stages of
      photoinduction of carotenoid biosynthesis in F. fujikuroi, and a possible
      modulation of WcoA activity by VvdA. An unexpected transcriptional induction by
      red light of vvdA, cryD and carRA genes suggest the participation of an
      additional red light-absorbing photoreceptor. 

PMID- 25774804
TI  - Risk factors for death from Influenza A(H1N1)pdm09, State of Sao Paulo, Brazil,
      2009.
AB  - This case-control study aimed to assess the risk factors for death from influenza
      A(H1N1)pdm09 in patients with laboratory confirmation, who had severe acute
      respiratory illness-SARI and were hospitalized between June 28th and August 29th
      2009, in the metropolitan regions of Sao Paulo and Campinas, Brazil. Medical
      charts of all the 193 patients who died (cases) and the 386 randomly selected
      patients who recovered (controls) were investigated in 177 hospitals. Household
      interviews were conducted with those who had survived and the closest relative of
      those who had died. 73.6% of cases and 38.1% of controls were at risk of
      developing influenza-related complications. The 18-to-59-year age group (OR =
      2.31, 95%CI: 1.31-4.10 (reference up to 18 years of age)), presence of risk
      conditions for severity of influenza (OR = 1.99, 95%CI: 1.11-3.57, if one or OR =
      6.05, 95%CI: 2.76-13.28, if more than one), obesity (OR = 2.73, 95%CI: 1.28
      5.83), immunosuppression (OR = 3.43, 95%CI: 1.28-9.19), and search for previous
      care associated with the hospitalization (OR = 3.35, 95%CI: 1.75-6.40) were risk
      factors for death. Antiviral treatment performed within 72 hours of the onset of
      symptoms (OR = 0.17, 95%CI: 0.08-0.37, if within 48hours, and OR = 0.30, 95%CI:
      0.11-0.81, if between 48 and 72 hours) was protective against death. The
      identification of high-risk patients and early treatment are important factors
      for reducing morbi-mortality from influenza. 

PMID- 25774803
TI  - The causes and consequences of changes in virulence following pathogen host
      shifts.
AB  - Emerging infectious diseases are often the result of a host shift, where the
      pathogen originates from a different host species. Virulence--the harm a pathogen
      does to its host-can be extremely high following a host shift (for example Ebola,
      HIV, and SARs), while other host shifts may go undetected as they cause few
      symptoms in the new host. Here we examine how virulence varies across host
      species by carrying out a large cross infection experiment using 48 species of
      Drosophilidae and an RNA virus. Host shifts resulted in dramatic variation in
      virulence, with benign infections in some species and rapid death in others. The
      change in virulence was highly predictable from the host phylogeny, with hosts
      clustering together in distinct clades displaying high or low virulence. High
      levels of virulence are associated with high viral loads, and this may determine
      the transmission rate of the virus.

PMID- 25774805
TI  - SYBR Green real-time PCR-RFLP assay targeting the plasmodium cytochrome B gene--a
      highly sensitive molecular tool for malaria parasite detection and species
      determination.
AB  - A prerequisite for reliable detection of low-density Plasmodium infections in
      malaria pre-elimination settings is the availability of ultra-sensitive and high
      throughput molecular tools. We developed a SYBR Green real-time PCR restriction
      fragment length polymorphism assay (cytb-qPCR) targeting the cytochrome b gene of
      the four major human Plasmodium species (P. falciparum, P. vivax, P. malariae,
      and P. ovale) for parasite detection and species determination with DNA extracted
      from dried blood spots collected on filter paper. The performance of cytb-qPCR
      was first compared against four reference PCR methods using serially diluted
      Plasmodium samples. The detection limit of the cytb-qPCR was 1 parasite/MUl
      (p/MUl) for P. falciparum and P. ovale, and 2 p/MUl for P. vivax and P. malariae,
      while the reference PCRs had detection limits of 0.5-10 p/MUl. The ability of the
      PCR methods to detect low-density Plasmodium infections was then assessed using
      2977 filter paper samples collected during a cross-sectional survey in Zanzibar,
      a malaria pre-elimination setting in sub-Saharan Africa. Field samples were
      defined as 'final positive' if positive in at least two of the five PCR methods.
      Cytb-qPCR preformed equal to or better than the reference PCRs with a sensitivity
      of 100% (65/65; 95%CI 94.5-100%) and a specificity of 99.9% (2910/2912; 95%CI
      99.7-100%) when compared against 'final positive' samples. The results indicate
      that the cytb-qPCR may represent an opportunity for improved molecular
      surveillance of low-density Plasmodium infections in malaria pre-elimination
      settings. 

PMID- 25774806
TI  - Tolerance associated gene expression following allogeneic hematopoietic cell
      transplantation.
AB  - Biologic markers of immune tolerance may facilitate tailoring of immune
      suppression duration after allogeneic hematopoietic cell transplantation (HCT).
      In a cross-sectional study, peripheral blood samples were obtained from tolerant
      (n = 15, median 38.5 months post-HCT) and non-tolerant (n = 17, median 39.5 post
      HCT) HCT recipients and healthy control subjects (n = 10) for analysis of immune
      cell subsets and differential gene expression. There were no significant
      differences in immune subsets across groups. We identified 281 probe sets unique
      to the tolerant (TOL) group and 122 for non-tolerant (non-TOL). These were
      enriched for process networks including NK cell cytotoxicity, antigen
      presentation, lymphocyte proliferation, and cell cycle and apoptosis.
      Differential gene expression was enriched for CD56, CD66, and CD14 human lineage
      specific gene expression. Differential expression of 20 probe sets between groups
      was sufficient to develop a classifier with > 90% accuracy, correctly classifying
      14/15 TOL cases and 15/17 non-TOL cases. These data suggest that differential
      gene expression can be utilized to accurately classify tolerant patients
      following HCT. Prospective investigation of immune tolerance biologic markers is
      warranted. 

PMID- 25774807
TI  - Improving hand hygiene behaviour among adolescents by a planning intervention.
AB  - To improve regular hand hygiene in adolescents, educational messages based on
      medical information have not been very successful. Therefore, a theory-guided
      self-regulatory intervention has been designed with a particular focus on
      planning strategies. A randomised controlled trial with 307 adolescents, aged 12
      18 years, was conducted in high schools. The control group received educational
      hand hygiene leaflets, whereas the experimental group received a self-regulatory
      treatment which required them to generate specific action plans and coping plans.
      Three times during one month, both groups received verbal reminder messages about
      planning to wash their hands properly. At one-month follow-up, hand hygiene
      behaviour as well as planning to practise hand hygiene were higher in the self
      regulation than in the education group (p < .01). Moreover, changes in planning
      levels operated as a mediator between experimental conditions and changes in
      behavioural outcomes. Teaching self-regulatory planning strategies may constitute
      a superior approach than educational messages to improve regular hand hygiene
      practice in adolescents.

PMID- 25774809
TI  - The Risk Environment of Heroin Use Initiation: Young Women, Intimate Partners,
      and "Drug Relationships".
AB  - This paper examines young women's initiation to heroin use in the context of an
      intimate relationship based on data from a small-scale ethno-epidemiology of
      heroin use in Ireland, 2007-2009. The epidemiological sample included 120 young
      people, and life history interviews were conducted with a sub-sample of 40 youth
      aged 16-25 years. A detailed analysis of the "risk environment" of young women's
      heroin initiation highlights a complex interplay between women's agency and
      intimate partner influence. It is argued that dichotomous representations of
      women as victims or emancipated consumers do not adequately capture the
      complexity of women's initiation journeys. The study's limitations are noted and
      implications for drug use prevention and harm reduction strategies are discussed.

PMID- 25774808
TI  - Enhanced functions of peripheral gammadelta T cells in chronic hepatitis B
      infection during interferon alpha treatment in vivo and in vitro.
AB  - BACKGROUND: gammadelta T cells play an important role in infectious, autoimmune,
      or neoplastic diseases. Here, a study was conducted to investigate the dynamic
      changes in phenotype and function of peripheral gammadelta T cells in patients
      with chronic hepatitis B (CHB) during pegylated-interferon (pegIFN)-alpha
      treatment, and to explore their roles in IFN-alpha therapy. METHODS: Total 15 CHB
      patients with pegIFN-alpha therapy and 6 healthy controls (HC) were enrolled in
      this study. Flow cytometry was used for the study of frequency of peripheral
      gammadelta T cells, subtypes, effector or memory gammadelta T cells, and also the
      IFN-gamma+, TNF-alpha+, CD107a+ or Granzyme B+ gammadelta T cells in 10 patients
      at week 0, 4, 8, 12, 24, 36 and 48 of treatment. Another 5 CHB patients and 6 HC
      were recruited for the gammadelta T cell isolation, and gene expression in
      gammadelta T cells was evaluated before or after IFN-alpha treatment in vitro.
      RESULTS: Although gammadeltaT cells decreased in CHB patients during pegIFN-alpha
      therapy, their capacities to produce TNF-alpha and to express CD107a were
      enhanced. More effector gammadeltaT cells (CD27-CD45RA+) were found in the
      response group than in non-response group. Furthermore, IFN-alpha boosted the
      expression of Mx2 and cytokine genes in gammadeltaT cells from CHB patients in
      vitro. CONCLUSION: IFN-alpha could enhance the cytokine production or
      cytotoxicity potential of gammadeltaT cells in vivo and in vitro. The enhanced
      function of gammadeltaT cells might contribute to the effect of IFN-alpha
      treatment.

PMID- 25774810
TI  - The doctor of nursing practice: a focus on clinical leadership.

PMID- 25774811
TI  - Building skills in organizational and systems changes: a DNP-FNP clinical
      curriculum.
AB  - DNP-prepared nurse practitioner leaders play a pivotal role in organizational
      change and quality improvement consistent with the IHI Triple Aim: improving
      quality of care, health of populations, and reducing cost. A DNP-FNP curriculum
      is described, designed to build students' leadership competencies for systems
      change in healthcare settings. 

PMID- 25774812
TI  - Central nervous system deficits in fetal alcohol spectrum disorder.
AB  - "Fetal alcohol spectrum disorders" is a nondiagnostic umbrella term encompassing
      the wide variations in clinical presentation among individuals that are
      prenatally exposed to alcohol. This article discusses brain development and
      central nervous system abnormalities and reviews prevention and interventions for
      these neurologic manifestations. 

PMID- 25774813
TI  - Pediatric developmental screenings: a primary care approach.
AB  - Early recognition of developmental delay is critical to providing comprehensive
      pediatric primary care. Advanced practice nurses must be aware of the guidelines
      for surveillance and developmental screening in children. This article discusses
      guidelines for screening, examples of screening tools, information for follow up,
      and referral for positive screenings. 

PMID- 25774819
TI  - [Management of non metastatic castration resistant prostate cancer].
AB  - OBJECTIVES: To review the features of non-metastatic castration resistant
      prostate cancer (nmCRPC) and analyze the available therapeutic options. A
      literature search was performed using MEDLINE/Pubmed and EMBASE databases.
      RESULTS: Non metastatic CRPC occurs when a properly castrated patient presents a
      PSA increase without radiological distant metastases. Up to now, the new
      therapies available for treatment of castration resistant prostate cancer (CRPC)
      have been tested and approved to be used in patients with distant metastases.
      Therefore there is a lack of proved effective therapies that have been
      traditionally covered with second line hormonal maneuvers. A major limitation of
      studies evaluating hormonal maneuvers is that they had as primary end point PSA
      decline assesment, generally equal or greater than 50%, on the basis that a
      response entailed a greater survival. However, and admitting that there is a
      relationship between PSA progression and survival, nowadays in a clinical trial
      changes in PSA are not accepted as surrogate for survival. For this reason there
      are no studies that directly show that second-line hormonal maneuvers prolong
      survival. Despite the absence of alternatives, some patients especially those
      worried about PSA progression, can benefit from these maneuvers. CONCLUSIONS:
      Second-line hormonal maneuvers can be an alternative in the absence of effective
      therapies, as long as they are well tolerated in well informed patients who
      refused observation or clinical trial inclusion.

PMID- 25774818
TI  - Extracorporeal life support as bridge to lung transplantation: a systematic
      review.
AB  - INTRODUCTION: Patients with acute respiratory failure requiring respiratory
      support with invasive mechanical ventilation while awaiting lung transplantation
      are at a high risk of death. Extracorporeal membrane oxygenation (ECMO) has been
      proposed as an alternative bridging strategy to mechanical ventilation. The aim
      of this study was to assess the current evidence regarding how the ECMO bridge
      influences patients' survival and length of hospital stay. METHODS: We performed
      a systematic review by searching PubMed, EMBASE and the bibliographies of
      retrieved articles. Three reviewers independently screened citation titles and
      abstracts and agreement was reached by consensus. We selected studies enrolling
      patients who received ECMO with the intention to bridge lung transplant. We
      included randomized controlled trials (RCTs), case-control studies and case
      series with ten or more patients. Outcomes of interest included survival and
      length of hospital stay. Quantitative data summaries were made when feasible.
      RESULTS: We identified 82 studies, of which 14 were included in the final
      analysis. All 14 were retrospective studies which enrolled 441 patients in total.
      Because of the broad heterogeneity among the studies we did not perform a meta
      analysis. The mortality rate of patients on ECMO before lung transplant and the
      one-year survival ranged from 10% to 50% and 50% to 90%, respectively. The
      intensive care and hospital length of stay ranged between a median of 15 to 47
      days and 22 to 47 days, respectively. There was a general paucity of high-quality
      data and significant heterogeneity among studies in the enrolled patients and
      technology used, which confounded analysis. CONCLUSIONS: In most of the studies,
      patients on ECMO while awaiting lung transplantation also received invasive
      mechanical ventilation. Therefore, whether ECMO as an alternative, rather than an
      adjunction, to invasive mechanical ventilation is a better bridging strategy to
      lung transplantation still remains an unresolved issue. ECMO support as a bridge
      for these patients could provide acceptable one-year survival. Future studies are
      needed to investigate ECMO as part of an algorithm of care for patients with end
      stage lung disease.

PMID- 25774820
TI  - [When should we perform a bone scintigraphy in patients with new diagnosis of
      asymptomatic prostate cancer in order to detect bone metastasis?].
AB  - OBJECTIVE: To define, based on PSA value, Gleason score (GS), clinical stage and
      age, those patients diagnosed with asymptomatic prostate cancer whose cases
      warrant further study of bone metastasis (BMet). METHODS: From January 2006 to
      May 2010, we evaluated 263 patients diagnosed with prostate cancer who were
      chosen for further study of bone scintigraphy following the consensus protocol
      accepted by the Ministry of Health of Andalusia (Integrated Andalusian Process
      Prostate Cancer-BPH). All selected studies met the criteria defined in the test
      indications: PSA >10 or Gleason score (GS) >=7 or positive biopsy of seminal
      vesicles, all without symptoms of bone pain. A multivariate analysis of potential
      predictive factors for positive bone scintigraphy was performed and cutoffs were
      determined by calculating the following diagnostic rates: sensitivity,
      specificity and positive and negative predictive values with their respective
      confidence intervals at 95% certainty. RESULTS: BMet were detected in 29 cases
      (11%). The average age of the patients with a positive bone scan was 65.5 and
      68.4 years in those with a negative result (p=0.03). Multivariate analysis showed
      that GS OR: 2.08 [95% CI (1.34 - 3.18)] (p<0.001) and PSA level 21-200 ng/ml OR:
      3.68 [95% CI (1.13-1.02)] (p<0.05) were independent predictive variables for
      positive bone scan. The cutoffs were estimated by ROC curve analysis, resulting
      in a cutoff of 16.18 ng/ml for PSA value and 7 for GS (larger area under the
      curve: 0.864 with a sensitivity of 94.5% and specificity of 47%). CONCLUSIONS: In
      the group of patients defined in our study, diagnosed with asymptomatic prostate
      cancer, the assessment of BMet using a bone scan should be carried out with a PSA
      level >= 16.18 ng/ml and GS >=7 as reference points.

PMID- 25774817
TI  - Genetics of type 2 diabetes-pitfalls and possibilities.
AB  - Type 2 diabetes (T2D) is a complex disease that is caused by a complex interplay
      between genetic, epigenetic and environmental factors. While the major
      environmental factors, diet and activity level, are well known, identification of
      the genetic factors has been a challenge. However, recent years have seen an
      explosion of genetic variants in risk and protection of T2D due to the technical
      development that has allowed genome-wide association studies and next-generation
      sequencing. Today, more than 120 variants have been convincingly replicated for
      association with T2D and many more with diabetes-related traits. Still, these
      variants only explain a small proportion of the total heritability of T2D. In
      this review, we address the possibilities to elucidate the genetic landscape of
      T2D as well as discuss pitfalls with current strategies to identify the elusive
      unknown heritability including the possibility that our definition of diabetes
      and its subgroups is imprecise and thereby makes the identification of genetic
      causes difficult. 

PMID- 25774821
TI  - [Quality of life after brachytherapy or robot-assisted radical prostatectomy for
      localized prostate cancer].
AB  - OBJECTIVES: To perform a systematic bibliographic review of the literature
      assessing the quality of life and complications of robotic prostatectomy (RP)
      versus low-dose rate brachytherapy (LDR-BT) in patients with localized prostate
      cancer (PCa). PubMed, EMBASE and Cochrane, Centre for Reviews and Dissemination,
      Emergency Care Research Institute, Web of Knowledge, Technology Evaluation
      Center, Clinical Evidence, Uptodate, Hayes and Drug Effectiveness Review Project.
      Systematic reviews and prospective studies comparing RP to LDR-BT in men with
      localized PCa were included. The primary outcome was quality of life and the
      secondary endpoint complications rate. RESULTS: Three systematic reviews and four
      prospective studies were included. RP showed better results than LDR-BT for SF-12
      physical domain (p<0.01) and faster recovery to pre-operative scores. LDR-BT
      improved scores for UCLAPCI questionnaire-urinary and sexual domains compared to
      RP during the first three years of follow-up (p<0.001). First postoperative year
      urinary incontinence rate was favorable for LDR-BT (88.0% vs 84.5%, p<0.001). No
      differences for intestinal function scores for the first three post-intervention
      years (p = 0.02) were found. Major complications of LDR-BT were gastrointestinal
      and genitourinary toxicity, although pooled weighted events rate of the studies
      was not analyzed. CONCLUSIONS: LDR-BT improves quality of life in terms of
      urinary and sexual function in patients with localized PCa vs RP during the first
      three years post-intervention.

PMID- 25774822
TI  - [Effectiveness of low-intensity extracorporeal shock wave therapy on patients
      with Erectile Dysfunction (ED) who have failed to respond to PDE5i therapy. A
      pilot study].
AB  - Low-intensity extracorporeal shock wave therapy (LIESWT) of the penis has
      recently emerged as a promising modality in the treatment of ED. OBJECTIVES: The
      objective of this paper is to assess the effectiveness and safety of LIESWT on
      patients with ED who have failed to respond to PDE5i treatment. METHODS: Open
      label, prospective, longitudinal observational study. The study involved an
      uncontrolled population of 25 patients. The treatment consisted in applying
      20,000 shock waves during a period of four weeks. In each session the patient
      received 5000 shock waves of 0.09 mJ/mm2: 1800 were applied on the penis (900 on
      each corpus cavernosum), and 3200 were applied on the perineum (1600 on each
      crus). During the active treatment and follow-up phases, all patients remained on
      their regular high on demand or once-a-day dose PDE5i schedules. MAIN OUTCOME
      MEASURE: Effectiveness was assessed by IIEF-6, SEP2, SEP3 and GAQ. Patients were
      considered to be responders whenever they improved on all three erection
      assessment parameters and respond positively to the GAQ at three months post
      treatment. Adverse events were recorded. Statistical variables were applied and
      findings were considered to be statistically significant whenever the P value
      was<0.05. RESULTS: Eighty percent (median age 63) of the patients (20/25)
      completed the study. Five patients were lost to follow-up and were excluded from
      the analysis. Sixty percent (60%) of the patients responded to the treatment,
      improved the 3 efficacy evaluating parameters and responded positively to the
      GAQ. The increase in mean IIEF-6 score was of 9 points after the third post
      treatment month. There were no patients reporting treatment-related adverse
      events. CONCLUSIONS: LIESWT for men with ED and that are PDE5i non-responders was
      safe and effective and restoring PDE5i response in more than 50% of patients.A
      large-scale multicenter study is required to determine the benefits of this
      treatment for ED.

PMID- 25774823
TI  - [Clinical and urodynamic results of alpha-blocker drug treatment in patients with
      lower urinary tract symptoms and benign prostatic hyperplasia].
AB  - OBJECTIVES: To analyse the improvement in both symptoms (IPSS questionnaire) and
      uroflowmetry parameters (Qmax) after treatment with different alpha-blockers in
      patients with LUTS and BPH. The efficacy of alpha-blocker treatment on urodynamic
      parameters was also analysed in some patients. METHODS: An epidemiological,
      retrospective, multi-centre, and observational study. Twenty-five (24) Spanish
      healthcare centres recruited 443 patients with LUTS and BPH, and no other
      concurrent urological disease, they were on treatment with alpha-blockers. The
      study variables (demographic, physical examination, IPSS, and urodynamic) were
      collected retrospectively at start of the study (at least 12 weeks after the
      start of treatment). Two-tailed statistical tests were performed with a 5%
      significance level using a SAS statistical software package version 9.0. RESULTS:
      The IPSS score improved after 12 weeks of treatment (p<0.0001). The quality of
      life perception significantly improved (p<0.0001). The voiding volume and Qmax
      increased (p<0.0001) and the post-void residual urine decreased (p<0.0001) after
      treatment both in patients with moderate and severe symptoms. Other than filling
      pressure and involuntary contraction amplitude (p>0.05), all cystomanometry
      parameters improved (p<0.05). There were statistically significant differences
      (p<0.05) in the pressure flow study values, except for the detrusor contractility
      rate. CONCLUSION: Alpha-blocker drug treatment of LUTS in patients with BPH leads
      to a significant improvement in symptoms and bladder voiding urodynamic
      parameters.

PMID- 25774824
TI  - When routine D-J implantation necessary during PNL?
AB  - OBJECTIVE: We investigated the characteristics of patients who underwent Double-J
      catheter (D-J) implantation, the risk factors for prolonged urine leakage (PUL),
      and prediction of patients who require medical treatment. METHODS: The data of
      535 adult patients who underwent PNL due to kidney stone disease between January
      2005 and December 2011 in our clinic were analyzed retrospectively. Patients were
      divided into 2 groups: Group 1 (n=77) (14.39%) included patients with Double-J
      catheter due to prolonged (> 24 h) urinary leakage and Group 2 (n=458) (85.61%)
      patients without urinary leakage. RESULTS: The mean stone burden was 951.94 +/-
      539.09 mm2 in Group 1, and 676.35 +/-296.65 mm2 in Group 2 (p<0.05). DJ catheter
      was implanted in 11.33% of the patients with stone burden below 1000 mm2 versus
      in 51.21% of the patients with stone burden above 1000 mm2. In Group 1, the
      number of patients with two or more accesses performed was 18.18, whereas in
      Group 2 it was 8.5% (p<0.05). Among all patients, DJ implantation was performed
      in 13.07% of patients with a single access versus 26.41% of patients with two or
      more accesses. Also, DJ catheter was implanted in 41.46%of patients with residual
      stones versus 12.14% of stone-free patients. Three patients with stone burden
      above 1000 mm2, two or more accesses, and residual stone, all of them required DJ
      implantation. CONCLUSION: DJ implantation due to PUL had approximately 5-fold
      increase stone burden above 1000 mm2, 2-fold increase in patients undergoing two
      or more access and 3-fold increase in patients with residual stones. Therefore,
      we think that the D-J implantation is highly advisable in case of a stone load
      above 1000 mm2, two or more accesses, and in patients with residual stones.

PMID- 25774825
TI  - [Urachal adenocarcinoma of the bladder, our experience in 20 years].
AB  - OBJECTIVE: To report two cases of urachal adenocarcinoma and to review the
      published literature. METHODS / RESULTS: We present a review of our urachal
      carcinoma cases from a third level hospital between 1990-2011 in an area of
      520.000 inhabitants. Both cases were middle aged men, consulting for repeated
      urine infections, and abdominal mass with hematuria and mucous discharge through
      the urethra. They were treated initially with partial cystectomy and adjuvant
      treatment with chemotherapy in one case, and chemo and radiotherapy in the other.
      The first case died in 3 years and the other is still alive after 4 years of
      follow up. CONCLUSIONS: Urachal adenocarcinomas of the bladder are rare tumors
      the natural history of which has not changed during the last years. Open partial
      cystectomy with en bloc resection of the bladder dome, urachus and the umbilicus
      is the standard treatment in localized stages, although minimal invasive
      techniques appear to have the same oncological outcomes. Pelvic lymphadenectomy
      is advised. Most of the patients are diagnosed at an advanced local or metastatic
      stage. There is a need to improve diagnostic techniques for early treatment and
      to find new chemotherapy protocols that can help to improve these patients'
      survival.

PMID- 25774826
TI  - [Management of chylous fistulas, a rare complication after urologic surgery].
AB  - OBJECTIVE: To analyze the different treatments for postoperative chylous
      fistulae. METHODS: A literature review of the main treatments for postoperative
      chylous fistula, providing our initial experience of two cases of patients with
      postsurgical chylorrea, with conservative treatment. RESULTS: There is very
      limited experience in the treatment of chylous ascites. According to the
      literature reviewed, Octreotide (somatostatin analogue) can be used, to decrease
      fistula output. Both our cases cases were treated successfully with subcutaneous
      octreotide, with drain debit decrease in about 3 days. CONCLUSIONS: The use of
      octreotide appears to be an effective treatment in the management of chylous
      fistulae, and it is suggested by some authors as first-line treatment in the
      management of these, thus decreasing the complications that can appear due to
      chyle loss.

PMID- 25774827
TI  - [Spontaneous enterocutaneous and rectovaginal fistula: potential complications
      during therapy with anti-angiogenic drugs in renal cancer].
AB  - We present two cases of enterovaginal and enterocutaneous fistulae associated to
      treatment with pazopanib, which is an angiogenesis inhibitor for the treatment of
      metastatic renal cancer. The times from drug administration and the first
      appearance of a fistula were 6 and 16 months, respectively. None of the cases had
      a history of surgery or radiotherapy in the area where the complication was
      observed. Enterovaginal and enterocutaneous fistula represent less than 1% of all
      published complications caused by the use of antiangiogenic drugs. However, they
      must be taken into account as the reported mortality rate is close to 30%. Given
      its low incidence, we believe that sharing this data is a great way to help
      specialists who have to treat these patients to take the necessary precautions
      and decide on an adequate approach. 

PMID- 25774829
TI  - The Addictive Personality.

PMID- 25774830
TI  - A massacred village community? Agent-based modelling sheds new light on the
      demography of the Neolithic mass grave of Talheim.
AB  - The virtual experiments presented below reveal the counterintuitive
      archaeological demography of the Neolithic mass grave of Talheim and underline
      the importance of distinguishing between the demographic structures of living and
      dead populations, as well as between attritional and catastrophic mortality
      patterns. We utilise a new agent-based modelling approach called Population &
      Cemetery Simulator based on the NetLogo programming language and the Behaviour
      Composer of the modelling4all project, which allows us to extrapolate from dead
      to living populations and vice versa. Contrary to received opinion, we argue that
      the population of the Neolithic mass grave holds specific demographic information
      only, as it represents a pure catastrophic mortality pattern, i.e. a living
      population at a single point in time rather than the population of a conventional
      cemetery. The first experiments illustrate why the published demographic data
      (e.g. mortality, life expectancy, mean age at death) is misleading. It is
      illogical to utilise mortality tables devised for conventional (attritional)
      cemeteries in the case of living populations. Modelled populations with the
      published mortality rates of the massacre site are, furthermore, unable to stand
      up to plausible human demographic circumstances. In the second part, we evaluate
      the actual demographic information content of the Talheim sample. Comparative
      modelling illustrates that the Talheim population appears to be similar to
      possible living populations based on the mortuary record of Schwetzingen, an
      isochronal site of the Linear Pottery Culture (LBK), and Barenthal, a site which
      dates back to the early medieval period (7th to 10th centuries). It is therefore
      very likely that the Talheim population is a representative sample of a living
      population in the LBK and might even represent a massacred village community in
      its entirety. 

PMID- 25774828
TI  - Transformation of the intestinal epithelium by the MSI2 RNA-binding protein.
AB  - The MSI2 RNA-binding protein is a potent oncogene playing key roles in
      haematopoietic stem cell homeostasis and malignant haematopoiesis. Here we
      demonstrate that MSI2 is expressed in the intestinal stem cell compartment, that
      its expression is elevated in colorectal adenocarcinomas, and that MSI2 loss-of
      function abrogates colorectal cancer cell growth. MSI2 gain-of-function in the
      intestinal epithelium in a drug-inducible mouse model is sufficient to phenocopy
      many of the morphological and molecular consequences of acute loss of the APC
      tumour suppressor in the intestinal epithelium in a Wnt-independent manner.
      Transcriptome-wide RNA-binding analysis indicates that MSI2 acts as a pleiotropic
      inhibitor of known intestinal tumour suppressors including Lrig1, Bmpr1a, Cdkn1a
      and Pten. Finally, we demonstrate that inhibition of the PDK-AKT-mTORC1 axis
      rescues oncogenic consequences of MSI2 induction. Taken together, our findings
      identify MSI2 as a central component in an unappreciated oncogenic pathway
      promoting intestinal transformation. 

PMID- 25774831
TI  - Active diffusion positions the nucleus in mouse oocytes.
AB  - In somatic cells, the position of the cell centroid is dictated by the
      centrosome. The centrosome is instrumental in nucleus positioning, the two
      structures being physically connected. Mouse oocytes have no centrosomes, yet
      harbour centrally located nuclei. We demonstrate how oocytes define their
      geometric centre in the absence of centrosomes. Using live imaging of oocytes,
      knockout for the formin 2 actin nucleator, with off-centred nuclei, together with
      optical trapping and modelling, we discover an unprecedented mode of nucleus
      positioning. We document how active diffusion of actin-coated vesicles, driven by
      myosin Vb, generates a pressure gradient and a propulsion force sufficient to
      move the oocyte nucleus. It promotes fluidization of the cytoplasm, contributing
      to nucleus directional movement towards the centre. Our results highlight the
      potential of active diffusion, a prominent source of intracellular transport,
      able to move large organelles such as nuclei, providing in vivo evidence of its
      biological function. 

PMID- 25774832
TI  - Metabolic pathways promoting cancer cell survival and growth.
AB  - Activation of oncogenes and loss of tumour suppressors promote metabolic
      reprogramming in cancer, resulting in enhanced nutrient uptake to supply
      energetic and biosynthetic pathways. However, nutrient limitations within solid
      tumours may require that malignant cells exhibit metabolic flexibility to sustain
      growth and survival. Here, we highlight these adaptive mechanisms and also
      discuss emerging approaches to probe tumour metabolism in vivo and their
      potential to expand the metabolic repertoire of malignant cells even further. 

PMID- 25774833
TI  - The telomere bouquet regulates meiotic centromere assembly.
AB  - The role of the conserved meiotic telomere bouquet has been enigmatic for over a
      century. We showed previously that disruption of the fission yeast bouquet
      impairs spindle formation in approximately half of meiotic cells. Surprisingly,
      bouquet-deficient meiocytes with functional spindles harbour chromosomes that
      fail to achieve spindle attachment. Kinetochore proteins and the centromeric
      histone H3 variant Cnp1 fail to localize to those centromeres that exhibit
      spindle attachment defects in the bouquet's absence. The HP1 orthologue Swi6 also
      fails to bind these centromeres, suggesting that compromised pericentromeric
      heterochromatin underlies the kinetochore defects. We find that centromeres are
      prone to disassembly during meiosis, but this is reversed by localization of
      centromeres to the telomere-proximal microenvironment, which is conducive to
      heterochromatin formation and centromere reassembly. Accordingly, artificially
      tethering a centromere to a telomere rescues the tethered centromere but not
      other centromeres. These results reveal an unanticipated level of control of
      centromeres by telomeres. 

PMID- 25774834
TI  - Force transmission during adhesion-independent migration.
AB  - When cells move using integrin-based focal adhesions, they pull in the direction
      of motion with large, ~100 Pa, stresses that contract the substrate. Integrin
      mediated adhesions, however, are not required for in vivo confined migration.
      During focal adhesion-free migration, the transmission of propelling forces, and
      their magnitude and orientation, are not understood. Here, we combine theory and
      experiments to investigate the forces involved in adhesion-free migration. Using
      a non-adherent blebbing cell line as a model, we show that actin cortex flows
      drive cell movement through nonspecific substrate friction. Strikingly, the
      forces propelling the cell forward are several orders of magnitude lower than
      during focal-adhesion-based motility. Moreover, the force distribution in
      adhesion-free migration is inverted: it acts to expand, rather than contract, the
      substrate in the direction of motion. This fundamentally different mode of force
      transmission may have implications for cell-cell and cell-substrate interactions
      during migration in vivo.

PMID- 25774835
TI  - Hypoxia-inducible TAp73 supports tumorigenesis by regulating the angiogenic
      transcriptome.
AB  - The functional significance of the overexpression of unmutated TAp73, a homologue
      of the tumour suppressor p53, in multiple human cancers is unclear, but raises
      the possibility of unidentified roles in promoting tumorigenesis. We show here
      that TAp73 is stabilized by hypoxia, a condition highly prevalent in tumours,
      through HIF-1alpha-mediated repression of the ubiquitin ligase Siah1, which
      targets TAp73 for degradation. Consequently, TAp73-deficient tumours are less
      vascular and reduced in size, and conversely, TAp73 overexpression leads to
      increased vasculature. Moreover, we show that TAp73 is a critical regulator of
      the angiogenic transcriptome and is sufficient to directly activate the
      expression of several angiogenic genes.  Finally, expression of TAp73 positively
      correlates with these angiogenic genes in several human tumours, and the
      angiogenic gene signature is sufficient to segregate the TAp73(Hi)- from
      TAp73(Low)-expressing tumours. These data demonstrate a pro-angiogenic role for
      TAp73 in supporting tumorigenesis, providing a rationale for its overexpression
      in cancers. 

PMID- 25774836
TI  - Nurse-Led Multidisciplinary Heart Failure Group Clinic Appointments: Methods,
      Materials, and Outcomes Used in the Clinical Trial.
AB  - BACKGROUND: The Self-management and Care of Heart Failure through Group Clinics
      Trial evaluated the effects of multidisciplinary group clinic appointments on
      self-care skills and rehospitalizations in high-risk heart failure (HF) patients.
      OBJECTIVE: The purpose of this article is to (1) describe key Self-management and
      Care of Heart Failure through Group Clinics Trial group clinic interactive
      learning strategies, (2) describe resources and materials used in the group
      clinic appointment, and (3) present results supporting this patient-centered
      group intervention. METHODS: This clinical trial included 198 HF patients
      (randomized to either group clinical appointments or to standard care). Data were
      collected from 72 group clinic appointments via patients' (1) group clinic
      session evaluations, (2) HF self-care behaviors skills, (3) HF-related
      discouragement and quality of life scores, and (4) HF-related reshopitalizations
      during the 12-month follow-up. Also, the costs of delivery of the group clinical
      appointments were tabulated. RESULTS: Overall, patients rated group appointments
      as 4.8 of 5 on the "helpfulness" in managing HF score. The statistical model
      showed a 33% decrease in the rate of rehospitalizations (incidence rate ratio,
      0.67) associated with the intervention over the 12-month follow-up period when
      compared with control patients (chi(2)1=3.9, P=.04). The total cost for
      implementing 5 group appointments was $243.58 per patient. CONCLUSION: The
      intervention was associated with improvements in HF self-care knowledge and home
      care behavior skills and managing their for HF care. In turn, better self-care
      was associated with reductions in HF-related hospitalizations.

PMID- 25774837
TI  - Examining the Feasibility of a Simple Intervention to Improve Blood Pressure
      Control for Primary Care Patients.
AB  - BACKGROUND: Blood pressure control remains a challenge despite the availability
      of effective antihypertensive agents. OBJECTIVE: This pilot study explored the
      feasibility of a simple, low-resource intervention to improve blood pressure
      control. METHODS: A convenience sample was drawn of 56 patients with hypertension
      from a primary care clinic. A preintervention-postintervention delivered by
      medical assistants involved prompts to providers to address blood pressure
      control with a visual aid indicating patients' current and target blood pressure
      in the context of a traffic light. RESULTS: Patients showed a significant
      reduction in mean systolic blood pressure (preintervention, 141.5 mm Hg, vs
      postintervention, 133.0 mm Hg; P = .002) and mean diastolic blood pressure
      (preintervention, 83.4 mm Hg, vs postintervention, 80.4 mm Hg; P = .049).
      CONCLUSION: In this pilot study, we established the feasibility of a brief,
      simple intervention to improve blood pressure control implemented by existing
      primary care practice clinical support staff, and preliminary data show that it
      can be effective in improving blood pressure control.

PMID- 25774838
TI  - Effect of Feedback Signal on Blood Pressure Self-regulation Capability in
      Individuals With Prehypertension or Stage I Hypertension: A Randomized Controlled
      Study.
AB  - OBJECTIVES: We aimed to determine the efficacy of an 8-week direct blood pressure
      (BP) biofeedback training program for prehypertensive or stage I hypertensive
      patients with a particular focus on the impact of the authenticity of feedback
      signals on the efficacy of BP regulation. DESIGNS: This study has a randomized,
      double-blind, parallel-group design. PARTICIPANTS AND METHODS: Fifty-nine
      individuals with ages from 18 to 64 years and who met the criteria for the
      diagnosis of prehypertenion or stage 1 hypertension participated in this study.
      The participants were referrals from physicians or community-dwelling volunteers.
      No participants had taken antihypertensive medication within the previous 2
      months prior to enrollment. The participants were randomly assigned to the
      biofeedback group (n = 31) trained with real-time BP feedback signals or the
      control group (n = 28) trained with pseudofeedback signals. The primary outcome
      measures were systolic BP (SBP) and diastolic BP (DBP). Systolic BP and DBP were
      assessed at baseline, 1 week after training (week 9), and 8 weeks after training
      (week 16) in both groups. Only 54 participants had week 16 data. RESULTS: The
      changes in SBP and DBP from baseline to week 9, from baseline to week 16, and
      from week 9 to week 16 were not significantly different between the groups (All P
      > 0.05). Both groups were able to significantly decrease BP after completing the
      training. A percentage of 45.2% of the participants in the biofeedback group and
      63.0% of the participants in the control group lowered their SBP by 5 mm Hg or
      more at week 9. The SBP-lowering effects were also maintained for at least 8
      weeks after the completion of training. CONCLUSIONS: The equivalent magnitude of
      BP reduction between the 2 study groups suggests that repeated practice in BP
      self-regulation was more likely responsible for the efficacy of direct BP
      biofeedback training than was the type of feedback signals.

PMID- 25774839
TI  - Influence of Gender and Age on the Peripheral Immune Response in Stroke.
AB  - BACKGROUND: Women and men have unique stroke risk factors and can experience
      different poststroke infections. OBJECTIVE: The aim of this study is to determine
      the influence of gender, age, and risk factors on the peripheral immune response
      in stroke/transient ischemic attack (TIA). METHOD: A total of 192 adult acute
      stroke/TIA cases were analyzed for age, gender, risk factors for stroke/TIA, and
      white blood cell with differential count. chi Test and analysis of variance were
      conducted to test for differences between genders and age groups related to
      stroke risk factors and the immune response. Growth modeling was used to test for
      trended differences in the immune response. RESULTS: Women were 4 years older
      than men; fewer women had strokes in the younger age group (<79 years) and more
      men currently smoked. Trended lymphocyte percentages for the young and old
      (slope, P = .04; pattern, P = .02) and admission monocyte percentages by gender
      were significantly different (P = .01). CONCLUSIONS: Age influenced trended
      lymphocyte numbers and gender influenced monocyte percentage on admission.

PMID- 25774840
TI  - Multimedia Exercise Training Program Improves Distance Walked, Heart Rate
      Recovery, and Self-efficacy in Cardiac Surgery Patients.
AB  - BACKGROUND: Patient education has been shown to be more effective when delivered
      using multimedia than written materials. However, the effects of using multimedia
      to assist patients in cardiac rehabilitation have not been investigated.
      OBJECTIVE: The purpose of this study is to examine the effect of an inpatient
      multimedia exercise training program on distance walked in the 6-minute walking
      test (6MWT), heart rate recovery, and walking self-efficacy of patients who had
      undergone heart surgery. METHODS: For this longitudinal quasi-experimental study,
      60 consecutive patients were assigned to an experimental (n = 20; inpatient
      multimedia exercise training program) or control (n = 40; routine care) group.
      Data were collected at 3 times (before surgery, 1 to 2 days before hospital
      discharge, and 1 month after hospital discharge) and analyzed with the
      generalized estimating equation approach. RESULTS: Most subjects were men
      (66.7%), had a mean age of 61.32 +/- 13.4 years and left ventricular ejection
      fraction of 56.96% +/- 13.28%, and underwent coronary artery bypass graft surgery
      (n = 34, 56.7%). Subjects receiving the exercise training program showed
      significantly greater improvement than those in the control group in the 6MWT
      walking distance (P < .001), heart rate recovery (P = .04), and self-efficacy (P
      = .002) at hospital discharge. Furthermore, the intervention effects on 6MWT
      distance (P < .001) and self-efficacy (P < .001) were sustained at 1 month after
      hospital discharge. CONCLUSION: Our inpatient multimedia exercise training
      program safely improved distance walked in the 6MWT, heart rate recovery, and
      self-efficacy at hospital discharge in patients after heart surgery and
      maintained their improvement in 6MWT and self-efficacy 1 month later.

PMID- 25774842
TI  - Facilitators and Barriers of Heart Surgery Discharge: Patients' and Nurses'
      Narrative Accounts.
AB  - BACKGROUND: Optimal patient recovery from open-heart surgery relies on effective
      discharge planning and education. However, the nature of the discharge experience
      has not been clearly described. OBJECTIVE: The study purpose is to explore
      patients' and nurses' narrative accounts of the facilitators and barriers of
      heart surgery discharge. METHODS: A qualitative study was employed using a
      narrative methodology that elicited and analyzed stories. This research was
      conducted in a large, urban hospital in Ontario, Canada. A total of 17 patients
      and nurses were recruited. Five female and 5 male patients were recruited from a
      preoperative clinic. Ages ranged from 37 to 80 years. Seven nurses were recruited
      from inpatient cardiovascular units. They had 2 to 19 years of cardiovascular
      nursing experience. Semistructured, narrative-based interviews were conducted.
      Two interviews were conducted with each patient at 1 week after discharge and at
      4 to 6 weeks. One interview was conducted with each nurse. RESULTS: Findings
      indicate that although the preoperative period was identified as an effective
      time for discharge preparation, the patient's cognitive capacity was limited
      during the postoperative phase of surgery. Both nurses and patients also found
      that insufficient time impeded the discharge process and limited individualized
      discussions. The structured and standardized delivery of discharge information
      affected patients' capacity to apply it to the particularities in their own lives
      and homes. The fostering of therapeutic relationships created a space where
      patients felt comfortable sharing their concerns and nurses learned more about
      patients and thus could better tailor the discharge approach. CONCLUSIONS: Study
      recommendations include group and scenario-based education in which patients and
      nurses brainstorm about how to apply the discharge information to the
      particularities of patients' lives and homes. Provision of support needs to be
      bolstered during the home period, where patients have timely opportunities to
      discuss their concerns and questions with practitioners or possibly peers.

PMID- 25774841
TI  - Health-Related Quality of Life, Functional Status, and Cardiac Event-Free
      Survival in Patients With Heart Failure.
AB  - BACKGROUND: Health-related quality of life (HRQOL), functional status, and
      cardiac event-free survival are outcomes used to assess the effectiveness of
      interventions in patients with heart failure (HF). However, the nature of the
      relationships among HRQOL, functional status, and cardiac event-free survival
      remains unclear. OBJECTIVE: The purpose of this study is to examine the nature of
      the relationships among HRQOL, functional status, and cardiac event-free survival
      in patients with HF. METHODS: This was a prospective, observational study of 313
      patients with HF that was a secondary analysis from a registry. At baseline,
      patient demographic and clinical data were collected. Health-related quality of
      life was assessed using the Minnesota Living With Heart Failure Questionnaire and
      functional status was measured using the Duke Activity Status Index. Cardiac
      event-free survival data were obtained by patient interview, hospital database,
      and death certificate review. Multiple linear and Cox regressions were used to
      explore the relationships among HRQOL, functional status, and cardiac event-free
      survival while adjusting for demographic and clinical factors. RESULTS:
      Participants (n = 313) were men (69%), white (79%), and aged 62 +/- 11 years.
      Mean left ventricular ejection fraction was 35% +/- 14%. The mean HRQOL score of
      32.3 +/- 20.6 indicated poor HRQOL. The mean Duke Activity Status Index score of
      16.2 +/- 12.9 indicated poor functional status. Cardiac event-free survival was
      significantly worse in patients who had worse HRQOL or poorer functional status.
      Patients who had better functional status had better HRQOL (P < .001). Health
      related quality of life was not a significant predictor of cardiac event-free
      survival after entering functional status in the model (P = .54), demonstrating
      that it was a mediator of the relationship between HRQOL and outcome. CONCLUSION:
      Functional status was a mediator between HRQOL and cardiac event-free survival.
      These data suggest that intervention studies to improve functional status are
      needed.

PMID- 25774843
TI  - Low-Dose Alteplase Infusion for the Treatment of Mechanical Aortic Valve
      Thrombosis: A Spotlight on the Importance of Medication Adherence.
AB  - A rare, yet serious, complication of mechanical heart valves is symptomatic
      obstructive prosthetic valve thrombosis. The risk of valve thrombosis is
      magnified in patients who are nonadherent to prescribed anticoagulation. In this
      case report, we describe a 48-year-old male patient with a history of mechanical
      aortic valve replacement surgery, who stopped taking prescribed warfarin therapy
      2 years before presentation and subsequently developed acute decompensated heart
      failure secondary to valvular dysfunction. Low-dose alteplase therapy was
      administered successfully with no bleeding complications and a complete return of
      valvular function. 

PMID- 25774844
TI  - The Situation-Specific Theory of Heart Failure Self-Care: Revised and Updated.
AB  - BACKGROUND: Since the situation-specific theory of heart failure (HF) self-care
      was published in 2008, we have learned much about how and why patients with HF
      take care of themselves. This knowledge was used to revise and update the theory.
      OBJECTIVE: The purpose of this article was to describe the revised, updated
      situation-specific theory of HF self-care. RESULT: Three major revisions were
      made to the existing theory: (1) a new theoretical concept reflecting the process
      of symptom perception was added; (2) each self-care process now involves both
      autonomous and consultative elements; and (3) a closer link between the self-care
      processes and the naturalistic decision-making process is described. In the
      revised theory, HF self-care is defined as a naturalistic decision-making process
      with person, problem, and environmental factors that influence the everyday
      decisions made by patients and the self-care actions taken. The first self-care
      process, maintenance, captures those behaviors typically referred to as treatment
      adherence. The second self-care process, symptom perception, involves body
      listening, monitoring signs, as well as recognition, interpretation, and labeling
      of symptoms. The third self-care process, management, is the response to symptoms
      when they occur. A total of 5 assumptions and 8 testable propositions are
      specified in this revised theory. CONCLUSION: Prior research illustrates that all
      3 self-care processes (ie, maintenance, symptom perception, and management) are
      integral to self-care. Further research is greatly needed to identify how best to
      help patients become experts in HF self-care.

PMID- 25774845
TI  - Illness Representations, Treatment Beliefs, Medication Adherence, and 30-Day
      Hospital Readmission in Adults With Chronic Heart Failure: A Prospective
      Correlational Study.
AB  - BACKGROUND: An estimated 5.1 million Americans have chronic heart failure, yet
      despite advances in its treatment, there has been no improvement in hospital
      readmissions among aging adult patients with chronic heart failure. OBJECTIVES:
      The purpose of this study is to investigate the relationships among illness
      representations, treatment beliefs, medication adherence, and 30-day hospital
      readmission for heart failure exacerbation in aging adults with chronic heart
      failure. METHOD: Using a prospective, correlational design, 96 older adults with
      a primary or secondary diagnosis of heart failure discharged to home from a
      hospital in the Southeastern United States participated in telephone surveys and
      follow-up telephone calls. Data analysis included correlation and logistic
      regression analyses. RESULTS: Participants were highly adherent to their
      medications. Individuals who did not believe their treatment was effective in
      controlling their HF were readmitted within 30 days of hospital discharge for HF
      exacerbation; that is, treatment control was inversely related to 30-day hospital
      readmission. In post hoc analyses, personal control was inversely related to
      dichotomized medication adherence and necessity-concern differential was directly
      related to dichotomized medication adherence. The necessity-concern differential,
      or the belief that medication necessity outweighed the concerns they had about
      their medicines, was a significant predictor of medication adherence. DISCUSSION:
      Nurses can use these study findings to help identify individuals who may be at
      risk of being nonadherent to their medications and hospital readmission.
      Recommendations for future research include replication with multiple sites, the
      addition of objective measures of medication adherence, investigation of both the
      cognitive and emotional pathways, and qualitative exploration of personal control
      in the context of medication adherence in HF.

PMID- 25774846
TI  - Adherence to Antihypertensive Medication in Older Adults With Hypertension.
AB  - BACKGROUND/OBJECTIVES: Effective prevention of cardiovascular events in people
      with hypertension requires optimal control of blood pressure. Despite advances in
      management, poor adherence to antihypertensive medications is often reported as
      the major reason attenuating treatment efficacy. Research has provided limited
      evidence of associations between illness perceptions, satisfaction with
      consultations, and medication adherence. The aim of this study is to identify
      factors significantly associated with medication adherence in a group of Chinese
      older adults with essential hypertension. DESIGN/SETTING/PARTICIPANTS: A cross
      sectional correlational study was conducted. Data were collected from 195 older
      adults (mean [SD] age, 76 [6.6] years) recruited from 12 community centers.
      MEASUREMENTS: The Illness Perception Questionnaire-Revised was used to measure
      illness perceptions, and the Medical Interview Satisfaction Scale was used to
      measure satisfaction with individual consultations. The Morisky Medication
      Adherence Scale was used to measure the extent of adherence to antihypertensive
      medications. Multivariate logistic regression analysis was performed to examine
      factors, including illness perceptions, consultation satisfaction, and
      demographic and clinical characteristics, that were significantly associated with
      medication adherence. RESULTS: More than half of the respondents (55.9%)
      acknowledged some degree of medication nonadherence. Older age, living alone, and
      perception related to treatment control were independently associated with
      increased odds of medication adherence, with odds ratios ranging from 1.14 to
      1.92 (P < .05). CONCLUSION: The results highlight the importance of cultivating
      positive beliefs that hypertension is amenable to control by treatment.
      Furthermore, the adherence behavior of those of younger individuals and living
      with family should be closely monitored.

PMID- 25774847
TI  - Commentary on "Effect of Feedback Signal on Blood Pressure Self-regulation
      Capability in Individuals With Prehypertension or Stage I Hypertension: A
      Randomized Controlled Study".

PMID- 25774848
TI  - Genetic and functional characterization of clonally derived adult human brown
      adipocytes.
AB  - Brown adipose tissue (BAT) acts in mammals as a natural defense system against
      hypothermia, and its activation to a state of increased energy expenditure is
      believed to protect against the development of obesity. Even though the existence
      of BAT in adult humans has been widely appreciated, its cellular origin and
      molecular identity remain elusive largely because of high cellular heterogeneity
      within various adipose tissue depots. To understand the nature of adult human
      brown adipocytes at single cell resolution, we isolated clonally derived
      adipocytes from stromal vascular fractions of adult human BAT from two
      individuals and globally analyzed their molecular signatures. We used RNA
      sequencing followed by unbiased genome-wide expression analyses and found that a
      population of uncoupling protein 1 (UCP1)-positive human adipocytes possessed
      molecular signatures resembling those of a recruitable form of thermogenic
      adipocytes (that is, beige adipocytes). In addition, we identified molecular
      markers that were highly enriched in UCP1-positive human adipocytes, a set that
      included potassium channel K3 (KCNK3) and mitochondrial tumor suppressor 1
      (MTUS1). Further, we functionally characterized these two markers using a loss-of
      function approach and found that KCNK3 and MTUS1 were required for beige
      adipocyte differentiation and thermogenic function. The results of this study
      present new opportunities for human BAT research, such as facilitating cell-based
      disease modeling and unbiased screens for thermogenic regulators. 

PMID- 25774849
TI  - Reversing excitatory GABAAR signaling restores synaptic plasticity and memory in
      a mouse model of Down syndrome.
AB  - Down syndrome (DS) is the most frequent genetic cause of intellectual disability,
      and altered GABAergic transmission through Cl(-)-permeable GABAA receptors
      (GABAARs) contributes considerably to learning and memory deficits in DS mouse
      models. However, the efficacy of GABAergic transmission has never been directly
      assessed in DS. Here GABAAR signaling was found to be excitatory rather than
      inhibitory, and the reversal potential for GABAAR-driven Cl(-) currents (ECl) was
      shifted toward more positive potentials in the hippocampi of adult DS mice.
      Accordingly, hippocampal expression of the cation Cl(-) cotransporter NKCC1 was
      increased in both trisomic mice and individuals with DS. Notably, NKCC1
      inhibition by the FDA-approved drug bumetanide restored ECl, synaptic plasticity
      and hippocampus-dependent memory in adult DS mice. Our findings demonstrate that
      GABA is excitatory in adult DS mice and identify a new therapeutic approach for
      the potential rescue of cognitive disabilities in individuals with DS. 

PMID- 25774851
TI  - Quantitative Contrast-Enhanced Magnetic Resonance Lymphangiography of the Upper
      Limbs in Breast Cancer Related Lymphedema: An Exploratory Study.
AB  - BACKGROUND: Contrast-Enhanced Magnetic Resonance Lymphangiography (CE-MRL)
      presents some limitations: (i) it does not quantify lymphatic functionality; and
      (ii) enhancement of vascular structures may confound image interpretation.
      Furthermore, although CE-MRL is well described in the published literature for
      the lower limbs, there is a paucity of data with regards to its use in the upper
      limbs. In this proof-of-principle study, we propose a new protocol to perform CE
      MRL in the upper limbs of patients with breast cancer-related lymphedema (BCRL)
      which addresses these limitations. METHODS AND RESULTS: CE-MRL was performed
      using a previously published (morphological) protocol and the proposed protocol
      (quantitative) on both the ipsilateral (abnormal) and contralateral (normal) arms
      of patients with BCRL. The quantitative protocol employs contrast agent (CA)
      intradermal injections at a lower concentration to prevent T2*-related signal
      decay. Both protocols provided high-resolution three-dimensional images of upper
      limb lymphatic vessels. CA uptake curves were utilized to distinguish between
      lymphatic vessels and vascular structures. The quantitative protocol minimized
      venous enhancement and avoided spurious delays in lymphatic enhancement due to
      short T2* values, enabling correct CA uptake characterization. The quantitative
      protocol was therefore employed to measure the lymphatic fluid velocity, which
      demonstrated functional differences between abnormal and normal arms. The
      velocity values were in agreement with previously reported lymphoscintigraphy and
      near infra-red lymphangiography measurements. CONCLUSIONS: This work demonstrated
      the feasibility of CE-MRL of the upper limbs in patients with BRCL, introducing
      an advanced imaging and analysis protocol suitable for anatomical and functional
      study of the lymphatic system.

PMID- 25774852
TI  - An extraordinary complication of emergency cervical cerclage in a 20 weeks'
      gestation: cervicoisthmic rupture.

PMID- 25774850
TI  - Characterization of pancreatic NMDA receptors as possible drug targets for
      diabetes treatment.
AB  - In the nervous system, NMDA receptors (NMDARs) participate in neurotransmission
      and modulate the viability of neurons. In contrast, little is known about the
      role of NMDARs in pancreatic islets and the insulin-secreting beta cells whose
      functional impairment contributes to diabetes mellitus. Here we found that
      inhibition of NMDARs in mouse and human islets enhanced their glucose-stimulated
      insulin secretion (GSIS) and survival of islet cells. Further, NMDAR inhibition
      prolonged the amount of time that glucose-stimulated beta cells spent in a
      depolarized state with high cytosolic Ca(2+) concentrations. We also noticed
      that, in vivo, the NMDAR antagonist dextromethorphan (DXM) enhanced glucose
      tolerance in mice, and that in vitro dextrorphan, the main metabolite of DXM,
      amplified the stimulatory effect of exendin-4 on GSIS. In a mouse model of type 2
      diabetes mellitus (T2DM), long-term treatment with DXM improved islet insulin
      content, islet cell mass and blood glucose control. Further, in a small clinical
      trial we found that individuals with T2DM treated with DXM showed enhanced serum
      insulin concentrations and glucose tolerance. Our data highlight the possibility
      that antagonists of NMDARs may provide a useful adjunct treatment for diabetes. 

PMID- 25774853
TI  - Canine helper-dependent vectors production: implications of Cre activity and co
      infection on adenovirus propagation.
AB  - The importance of Cre recombinase to minimize helper vector (HV) contamination
      during helper-dependent adenovirus vectors (HDVs) production is well documented.
      However, Cre recombinase, by inducing DNA double-strand breaks (DSBs), can cause
      a reduced proliferation and genotoxic effects in cultured cells. In this work,
      Cre-expressing cell stability, co-infection and their relation to adenovirus
      amplification/HV contamination were evaluated to develop a production protocol
      for HD canine adenovirus type 2 (CAV-2) vectors. Long-term Cre expression reduced
      the capacity of MDCK-E1-Cre cells to produce CAV-2 by 7-fold, although cell
      growth was maintained. High HDV/HV MOI ratio (5:0.1) led to low HV contamination
      without compromising HDV yields. Indeed, such MOI ratio was sufficient to reduce
      HV levels, as these were similar either in MDCK-E1 or MDCK-E1-Cre cells. This
      raises the possibility of producing HDVs without Cre-expressing cells, which
      would circumvent the negative effects that this recombinase holds to the
      production system. Here, we show how Cre and MOI ratio impact adenovirus vectors
      yields and infectivity, providing key-information to design an improved
      manufacturing of HDV. Potential mechanisms to explain how Cre is specifically
      impacting cell productivity without critically compromising its growth are
      presented. 

PMID- 25774854
TI  - Customized partially covered biodegradable stent for anastomotic leakage after
      esophagojejunostomy.

PMID- 25774855
TI  - Hearing others' perspectives when we hear, "do everything!".

PMID- 25774856
TI  - Death among patients hospitalized with pneumonia: implications for hospital
      outcome measures.

PMID- 25774857
TI  - A comparison of random and post-accident urine opiate and opioid tests.
AB  - Opioid use is associated with poor reaction time, attention, balance and memory
      posing a potential threat to workplace safety. The purpose of this study is to
      determine if there is a statistical association between opiate/opioid use and
      work related accidents as measured by urine drug tests by comparing the
      proportion of opiate/opioid laboratory positive urine specimens for postaccident
      verses random samples. The prevalence of laboratory positive opiate/opioid tests,
      the odds ratio, Fisher's exact probability test and the population attributable
      risk were calculated for each comparison. This study found a statistically
      significant difference for opiate/opioid results favoring the post-accident
      group. 

PMID- 25774858
TI  - Wimbo: implications for risk of HIV infection among circumcised fishermen in
      Western Kenya.
AB  - Medical male circumcision has been shown to reduce the risk of heterosexual
      transmission of HIV infection in men by up to 60% in three randomised controlled
      trials. However, not much anthropological literature exists to provide a holistic
      understanding of sexual behaviour among migrating fishermen who have been
      circumcised. This qualitative study used cultural ecology theory and
      anthropological methods to develop a more holistic understanding of Luo
      fishermen's sexual behaviour after circumcision when they migrate (wimbo) to
      islands in western Kenya. Results from focus-group discussions show that during
      wimbo there is a deviation from community norms governing sexual expression,
      influenced by the belief that circumcision provides protection against HIV
      infection. Through the exchange of sex for fish, circumcised men access new
      sexual partners in the destination beaches and engage in risky sexual behaviours
      without any HIV prevention measures. The processes and practices associated with
      wimbo may therefore help explain why rates of HIV infection are increasing among
      fisherfolk despite new interventions to combat HIV. These results have relevant
      implications for HIV-related intervention and policy in sub-Saharan Africa. 

PMID- 25774859
TI  - B-type proto-oncogene-mutated tumors of colon cancer: promising therapeutic
      approaches.
AB  - PURPOSE OF REVIEW: B-type proto-oncogene (BRAF) mutations have been observed in
      about 10.8% of patients with colorectal cancer (CRC). These patients do not
      respond to standard therapy with anti-epidermal growth factor receptor kinase
      (EGFR). Here we review novel BRAF inhibitors that are currently being
      investigated in these tumors. RECENT FINDINGS: Clinical experience with the BRAF
      inhibitor vemurafenib in CRC suggests significant differences in response
      compared with melanoma. Based on preclinical data, resistance to BRAF inhibitors
      employs alternative signaling pathways that in turn induce cell proliferation and
      survival. Therapeutic strategies that combine BRAF inhibitors in addition to
      targeted therapy with anti-EGFR monoclonal antibodies and phosphoinositide 3
      kinase pathway inhibitors or standard therapy have yielded promising results in
      preclinical models and some reported cases. SUMMARY: Results from current
      clinical trials that are exploring novel BRAF inhibitors and others that employ
      combined therapy are eagerly awaited for the treatment of BRAF-mutated CRC. VIDEO
      ABSTRACT: http://links.lww.com/COON/A13.

PMID- 25774860
TI  - Mucositis: pathobiology and management.
AB  - PURPOSE OF REVIEW: Oral mucositis remains a frequent debilitating toxicity
      associated with drug and radiation regimens used to treat cancer. This review
      highlights the recent understanding of the biological basis, risk factors for,
      and management for oral mucositis. RECENT FINDINGS: Prevalence and incidence data
      for mucositis are inconsistent and often underreported. The pathogenesis of
      mucositis encompasses a sequence of biological events possibly influenced by the
      oral microbiome and environment. Despite its frequency and severity, there is
      currently no effective treatment available for the majority of patients at risk.
      However, with the better understanding of the pathogenesis of mucositis a number
      of new drugs and biological agents are under investigation. Genome-wide risk
      prediction tools will allow the identification of patients at risk of developing
      mucositis. SUMMARY: Oral mucositis is a common complication of cancer treatment
      that may negatively impact the patient's cancer treatment outcome. Despite its
      frequency and consequences, the lack of effective interventions has frustrated
      patients and caregivers. Fortunately, a broad range of mechanistically targeted
      compounds are being developed.

PMID- 25774861
TI  - One Last Day.

PMID- 25774864
TI  - Suppressing bacterial interaction with copper surfaces through graphene and
      hexagonal-boron nitride coatings.
AB  - Understanding biological interaction with graphene and hexagonal-boron nitride (h
      BN) membranes has become essential for the incorporation of these unique
      materials in contact with living organisms. Previous reports show contradictions
      regarding the bacterial interaction with graphene sheets on metals. Here, we
      present a comprehensive study of the interaction of bacteria with copper
      substrates coated with single-layer graphene and h-BN. Our results demonstrate
      that such graphitic coatings substantially suppress interaction between bacteria
      and underlying Cu substrates, acting as an effective barrier to prevent physical
      contact. Bacteria do not "feel" the strong antibacterial effect of Cu, and the
      substrate does not suffer biocorrosion due to bacteria contact. Effectiveness of
      these systems as barriers can be understood in terms of graphene and h-BN
      impermeability to transfer Cu(2+) ions, even when graphene and h-BN domain
      boundary defects are present. Our results seem to indicate that as-grown graphene
      and h-BN films could successfully protect metals, preventing their corrosion in
      biological and medical applications. 

PMID- 25774865
TI  - LAMB1 polymorphism is associated with autism symptom severity in Korean autism
      spectrum disorder patients.
AB  - BACKGROUND: LAMB1 encodes laminin beta-1, which is expressed during early
      development of the human nervous system, and could be involved in the
      pathogenesis of neurodevelopmental disorders. AIMS: In our study, we aimed to
      investigate whether single nucleotide polymorphisms (SNPs) in LAMB1 were
      associated with autism spectrum disorder (ASD) and with related clinical
      severities of ASD. METHODS: Two coding SNPs (rs20556 and rs25659) and two
      intronic SNPs (rs2158836 and rs2237659) were compared between 180 patients with
      ASD and 147 healthy control subjects using direct sequencing. The Korean version
      of the Childhood Autism Rating Scale (K-CARS) was used to assess clinical
      severities. Multiple logistic regression models were employed to analyze genetic
      data, and associations with symptom severity were tested with the Kruskal-Wallis
      and the Mann-Whitney U tests. RESULTS: None of the four examined SNPs was
      associated with ASD risk. However, the GG genotype of rs2158836 was associated
      with more severe symptoms for the "object use" and "non-verbal communication"
      measures. CONCLUSIONS: The results of our study suggest the association between
      rs2158836 polymorphisms and symptom severity in ASD.

PMID- 25774866
TI  - Future of specialised roles in allied health practice: who is responsible?
AB  - Allied health professions have developed specialised advanced and extended scope
      roles over the past decade, for the benefit of patient outcomes, allied health
      professionals' satisfaction and to meet labour and workforce demands. There is an
      essential need for formalised, widely recognised training to support these roles,
      and significant challenges to the delivery of such training exist. Many of these
      roles function in the absence of specifically defined standards of clinical
      practice and it is unclear where the responsibility for training provision lies.
      In a case example ofphysiotherapy practice in the intensive care unit, clinical
      placements and independence of practice are not core components of undergraduate
      physiotherapy degrees. Universities face barriers to the delivery of postgraduate
      specialised training and, although hospital physiotherapy departments are ideally
      placed, resources for training are lacking and education is not traditionally
      considered part of healthcare service providers' core business. Substantial
      variability in training, and its evaluation, leads to variability in practice and
      may affect patient outcomes. Allied health professionals working in specialised
      roles should develop specific clinical standards ofpractice, restructure models
      ofhealth care delivery to facilitate training, continue to develop the evidence
      base for their roles and target and evaluate training efficacy to achieve
      independent practice in a cost-effective manner. Healthcare providers must work
      with universities, the vocational training sector and government to optimise the
      ability of allied health to influence decision making and care outcomes for
      patients.

PMID- 25774863
TI  - Back to the future: transgenerational transmission of xenobiotic-induced
      epigenetic remodeling.
AB  - Epigenetics, or regulation of gene expression independent of DNA sequence, is the
      missing link between genotype and phenotype. Epigenetic memory, mediated by
      histone and DNA modifications, is controlled by a set of specialized enzymes,
      metabolite availability, and signaling pathways. A mostly unstudied subject is
      how sub-toxic exposure to several xenobiotics during specific developmental
      stages can alter the epigenome and contribute to the development of disease
      phenotypes later in life. Furthermore, it has been shown that exposure to low
      dose xenobiotics can also result in further epigenetic remodeling in the germ
      line and contribute to increase disease risk in the next generation
      (multigenerational and transgenerational effects). We here offer a perspective on
      current but still incomplete knowledge of xenobiotic-induced epigenetic
      alterations, and their possible transgenerational transmission. We also propose
      several molecular mechanisms by which the epigenetic landscape may be altered by
      environmental xenobiotics and hypothesize how diet and physical activity may
      counteract epigenetic alterations. 

PMID- 25774867
TI  - Impact of Gender on Long-Term Treatment Outcomes of Highly Active Antiretroviral
      Therapy (HAART) in the TREAT Asia HIV Observational Database.

PMID- 25774869
TI  - Corrigendum.

PMID- 25774868
TI  - MoveU? Assessing a Social Marketing Campaign to Promote Physical Activity.
AB  - OBJECTIVE: MoveU is a social marketing initiative aimed at increasing moderate-to
      vigorous physical activity (MVPA) among undergraduate students. Using the
      Hierarchy of Effects model (HOEM), this study identified awareness of MoveU and
      examined associations between awareness, outcome expectations, self-efficacy,
      intentions, and MVPA. PARTICIPANTS: Students (N = 2,784) from a Canadian
      university in March 2013. METHODS: A secondary analysis of the National College
      Health Assessment-II survey and measures specific to the MoveU campaign. The main
      associations were examined in a path analysis. RESULTS: MoveU awareness (36.4%)
      was lower than other well-established university health campaigns. Younger
      students, females, and individuals living on campus were more likely to be aware
      of MoveU. The HOEM was supported, and improvements in model fit were evident,
      with additional direct relationships between outcome expectancy and intention,
      and between self-efficacy and MVPA. CONCLUSIONS: The intended population was
      aware of the campaign. The HOEM was useful in the development and evaluation of
      the MoveU campaign. Longitudinal studies are needed to further test the efficacy
      of the HOEM in the social marketing of physical activity.

PMID- 25774870
TI  - New Selaginellin derivatives from Selaginella tamariscina.
AB  - Two new selaginellin derivatives selaginellin P (1) and selaginellin Q (2) were
      isolated from Selaginella tamariscina. The structures of 1 and 2 were established
      as 2,4'-dihydroxy-4-methyl-3-[(4-hydroxyphenyl)ethynyl]biphene (1) and 2,4'
      dihydroxy-3-[(4-hydroxyphenyl)ethynyl]biphene (2) on the basis of spectroscopic
      means including HR-ESI-MS, 1D, and 2D NMR experiments. 

PMID- 25774873
TI  - Correction: simulating free-roaming cat population management options in open
      demographic environments.

PMID- 25774872
TI  - The nuclear receptor DAF-12 regulates nutrient metabolism and reproductive growth
      in nematodes.
AB  - Appropriate nutrient response is essential for growth and reproduction. Under
      favorable nutrient conditions, the C. elegans nuclear receptor DAF-12 is
      activated by dafachronic acids, hormones that commit larvae to reproductive
      growth. Here, we report that in addition to its well-studied role in controlling
      developmental gene expression, the DAF-12 endocrine system governs expression of
      a gene network that stimulates the aerobic catabolism of fatty acids. Thus,
      activation of the DAF-12 transcriptome coordinately mobilizes energy stores to
      permit reproductive growth. DAF-12 regulation of this metabolic gene network is
      conserved in the human parasite, Strongyloides stercoralis, and inhibition of
      specific steps in this network blocks reproductive growth in both of the
      nematodes. Our study provides a molecular understanding for metabolic adaptation
      of nematodes to their environment, and suggests a new therapeutic strategy for
      treating parasitic diseases. 

PMID- 25774874
TI  - Synthesis of pyrazole containing alpha-amino acids via a highly regioselective
      condensation/aza-Michael reaction of beta-aryl alpha,beta-unsaturated ketones.
AB  - A synthetic approach for the preparation of a new class of highly conjugated
      unnatural alpha-amino acids bearing a 5-arylpyrazole side-chain has been
      developed. Horner-Wadsworth-Emmons reaction of an aspartic acid derived beta-keto
      phosphonate ester with a range of aromatic aldehydes gave beta-aryl alpha,beta
      unsaturated ketones. Treatment of these with phenyl hydrazine followed by
      oxidation allowed the regioselective synthesis of pyrazole derived alpha-amino
      acids. As well as evaluating the fluorescent properties of the alpha-amino acids,
      their synthetic utility was also explored with the preparation of a sulfonyl
      fluoride derivative, a potential probe for serine proteases. 

PMID- 25774875
TI  - The Use of Pulse Oximetry to Determine Hypoxemia in Acute Exacerbations of COPD.
AB  - BACKGROUND: There is little evidence that the guideline-recommended oxygen
      saturation of 92% is the best cut-off point for detecting hypoxemia in COPD
      exacerbations. OBJECTIVE: To detect and validate pulse oximetry oxygen saturation
      cut-off values likely to detect hypoxemia in patients with aeCOPD, to explore the
      correlation between oxygen saturation measured by pulse oximetry and hypoxemia or
      hypercapnic respiratory failure. METHODOLOGY: Cross-sectional study nested in the
      IRYSS-COPD study with 2,181 episodes of aeCOPD recruited between 2008 and 2010 in
      16 hospitals belonging to the Spanish Public Health System. Data collected
      include determination of oxygen saturation by pulse oximetry upon arrival in the
      emergency department (ED), first arterial blood gasometry values,
      sociodemographic information, background medical history and clinical variables
      upon ED arrival. Logistic regression models were performed using as the dependent
      variables hypoxemia (PaO2 < 60 mmHg) and hypercapnic respiratory failure (PaO2 <
      60 mmHg and PaCO2 > 45). Optimal cut-off points were calculated. RESULTS: The
      correlation coefficient between oxygen saturation and pO2 measured by arterial
      blood gasometry was 0.89. The area under the curve (AUC) for the hypoxemia model
      was 0.97 (0.96-0.98) and the optimal cut-off point for hypoxemia was an oxygen
      saturation of 90%. The AUC for hypercapnic respiratory failure was 0.90 (0.87
      0.92) and the optimal cut-off point was an oxygen saturation of 88%. CONCLUSIONS:
      Our results support current recommendations for ordering blood gasometry based on
      pulse oximetry oxygen saturation cut-offs for hypoxemia. We also provide easy to
      use formulae to calculate pO2 from oxygen saturation measured by pulse oximetry.

PMID- 25774876
TI  - RECQ1 interacts with FEN-1 and promotes binding of FEN-1 to telomeric chromatin.
AB  - RecQ helicases are a family of highly conserved proteins that maintain genomic
      stability through their important roles in replication restart mechanisms.
      Cellular phenotypes of RECQ1 deficiency are indicative of aberrant repair of
      stalled replication forks, but the molecular functions of RECQ1, the most
      abundant of the five known human RecQ homologues, have remained poorly
      understood. We show that RECQ1 associates with FEN-1 (flap endonuclease-1) in
      nuclear extracts and exhibits direct protein interaction in vitro. Recombinant
      RECQ1 significantly stimulated FEN-1 endonucleolytic cleavage of 5'-flap DNA
      substrates containing non-telomeric or telomeric repeat sequence. RECQ1 and FEN-1
      were constitutively present at telomeres and their binding to the telomeric
      chromatin was enhanced following DNA damage. Telomere residence of FEN-1 was
      dependent on RECQ1 since depletion of RECQ1 reduced FEN-1 binding to telomeres in
      unperturbed cycling cells. Our results confirm a conserved collaboration of human
      RecQ helicases with FEN-1 and suggest both overlapping and specialized roles of
      RECQ1 in the processing of DNA structure intermediates proposed to arise during
      replication, repair and recombination. 

PMID- 25774877
TI  - Beneficial effects of calcitriol on hypertension, glucose intolerance, impairment
      of endothelium-dependent vascular relaxation, and visceral adiposity in fructose
      fed hypertensive rats.
AB  - Besides regulating calcium homeostasis, the effects of vitamin D on vascular tone
      and metabolic disturbances remain scarce in the literature despite an increase
      intake with high-fructose corn syrup worldwide. We investigated the effects of
      calcitriol, an active form of vitamin D, on vascular relaxation, glucose
      tolerance, and visceral fat pads in fructose-fed rats. Male Wistar-Kyoto rats
      were divided into 4 groups (n = 6 per group). Group Con: standard chow diet for 8
      weeks; Group Fru: high-fructose diet (60% fructose) for 8 weeks; Group Fru-HVD:
      high-fructose diet as Group Fru, high-dose calcitriol treatment (20 ng / 100 g
      body weight per day) 4 weeks after the beginning of fructose feeding; and Group
      Fru-LVD: high-fructose diet as Group Fru, low-dose calcitriol treatment (10 ng /
      100 g body weight per day) 4 weeks after the beginning of fructose feeding.
      Systolic blood pressure was measured twice a week by the tail-cuff method. Blood
      was examined for serum ionized calcium, phosphate, creatinine, glucose,
      triglycerides, and total cholesterol. Intra-peritoneal glucose intolerance test,
      aortic vascular reactivity, the weight of visceral fat pads, adipose size, and
      adipose angiotensin II levels were analyzed at the end of the study. The results
      showed that the fructose-fed rats significantly developed hypertension, impaired
      glucose tolerance, heavier weight and larger adipose size of visceral fat pads,
      and raised adipose angiotensin II expressions compared with the control rats.
      High- and low-dose calcitriol reduced modestly systolic blood pressure, increased
      endothelium-dependent aortic relaxation, ameliorated glucose intolerance, reduced
      the weight and adipose size of visceral fat pads, and lowered adipose angiotensin
      II expressions in the fructose-fed rats. However, high-dose calcitriol treatment
      mildly increased serum ionized calcium levels (1.44 +/- 0.05 mmol/L). These
      results suggest a protective role of calcitriol treatment on endothelial
      function, glucose tolerance, and visceral adiposity in fructose-fed rats. 

PMID- 25774878
TI  - Adolescent substance use screening in primary care: Validity of computer self
      administered versus clinician-administered screening.
AB  - BACKGROUND: Computer self-administration may help busy pediatricians' offices
      increase adolescent substance use screening rates efficiently and effectively, if
      proven to yield valid responses. The CRAFFT screening protocol for adolescents
      has demonstrated validity as an interview, but a computer self-entry approach
      needs validity testing. The aim of this study was to evaluate the criterion
      validity and time efficiency of a computerized adolescent substance use screening
      protocol implemented by self-administration or clinician-administration. METHODS:
      Twelve- to 17-year-old patients coming for routine care at 3 primary care clinics
      completed the computerized screen by both self-administration and clinician
      administration during their visit. To account for order effects, we randomly
      assigned participants to self-administer the screen either before or after seeing
      their clinician. Both were conducted using a tablet computer and included
      identical items (any past-12-month use of tobacco, alcohol, drugs; past-3-month
      frequency of each; and 6 CRAFFT items). The criterion measure for substance use
      was the Timeline Follow-Back, and for alcohol/drug use disorder, the Adolescent
      Diagnostic Interview, both conducted by confidential research assistant interview
      after the visit. Tobacco dependence risk was assessed with the self-administered
      Hooked on Nicotine Checklist (HONC). Analyses accounted for the multisite cluster
      sampling design. RESULTS: Among 136 participants, mean age was 15.0 +/- 1.5
      years, 54% were girls, 53% were black or Hispanic, and 67% had >=3 prior visits
      with their clinician. Twenty-seven percent reported any substance use (including
      tobacco) in the past 12 months, 7% met criteria for an alcohol or cannabis use
      disorder, and 4% were HONC positive. Sensitivity/specificity of the screener were
      high for detecting past-12-month use or disorder and did not differ between
      computer and clinician. Mean completion time was 49 seconds (95% confidence
      interval [CI]: 44-54) for computer and 74 seconds (95% CI: 68-87) for clinician
      (paired comparison, P < .001). CONCLUSIONS: Substance use screening by computer
      self-entry is a valid and time-efficient alternative to clinician-administered
      screening.

PMID- 25774879
TI  - Hepatocyte nuclear factor 4 alpha is a key factor related to depression and
      physiological homeostasis in the mouse brain.
AB  - Major depressive disorder (MDD) is a common psychiatric disorder that involves
      marked disabilities in global functioning, anorexia, and severe medical
      comorbidities. MDD is associated with not only psychological and sociocultural
      problems, but also pervasive physical dysfunctions such as metabolic,
      neurobiological and immunological abnormalities. Nevertheless, the mechanisms
      underlying the interactions between these factors have yet to be determined in
      detail. The aim of the present study was to identify the molecular mechanisms
      responsible for the interactions between MDD and dysregulation of physiological
      homeostasis, including immunological function as well as lipid metabolism,
      coagulation, and hormonal activity in the brain. We generated depression-like
      behavior in mice using chronic mild stress (CMS) as a model of depression. We
      compared the gene expression profiles in the prefrontal cortex (PFC) of CMS and
      control mice using microarrays. We subsequently categorized genes using two web
      based bioinformatics applications: Ingenuity Pathway Analysis and The Database
      for Annotation, Visualization, and Integrated Discovery. We then confirmed
      significant group-differences by analyzing mRNA and protein expression levels not
      only in the PFC, but also in the thalamus and hippocampus. These web tools
      revealed that hepatocyte nuclear factor 4 alpha (Hnf4a) may exert direct effects
      on various genes specifically associated with amine synthesis, such as genes
      involved in serotonin metabolism and related immunological functions. Moreover,
      these genes may influence lipid metabolism, coagulation, and hormonal activity.
      We also confirmed the significant effects of Hnf4a on both mRNA and protein
      expression levels in the brain. These results suggest that Hnf4a may have a
      critical influence on physiological homeostasis under depressive states, and may
      be associated with the mechanisms responsible for the interactions between MDD
      and the dysregulation of physiological homeostasis in humans. 

PMID- 25774880
TI  - Gender-specific changes in well-being in older people with coronary heart
      disease: evidence from the English Longitudinal Study of Ageing.
AB  - OBJECTIVES: The objective of this study is to investigate gender-specific
      trajectories in well-being among older people with coronary heart disease (CHD)
      and to compare them with those of healthy people. METHOD: The study included a
      sample of 4496 participants from the first three waves of the English
      Longitudinal Study of Ageing (2002-2003 to 2006-2007). We measured well-being
      using quality of life (CASP-19; 'control', 'autonomy', 'pleasure' and 'self
      realization') and depressive caseness (three or more symptoms on the CESD-8;
      Centre for Epidemiologic Study Depression scale). RESULTS: After adjustment, at
      two- and four-years follow-ups, women had three points higher quality of life
      than men (p < 0.001). When looking at each quality of life's domain we found that
      women reported higher scores of autonomy compared to men. The gender difference
      in the probability of having depressive caseness reduced to 7 percentage points
      at four-year follow-up from 13 percentage points in the previous occasions. Men's
      quality of life declined progressively over time by 3 points (p < 0.001)
      (equivalent to the effect of having diabetes) but no changes in prevalence of
      depressive caseness were found. Women's quality of life only declined after four
      year follow-up by less than 2 points (p < 0.001), while in the same period their
      probability of reporting depressive caseness reduced by 6 percentage points (p <
      0.001). CONCLUSION: Women had better quality of life than men in the two and four
      years following a CHD event, and were not more likely than men to report
      depressive caseness in the long term. Men's quality of life deteriorated
      progressively over time, among women it did not deteriorate in the first two
      years following a CHD event; women had a long-term improvement in depressive
      caseness.

PMID- 25774882
TI  - Dithiol-based modification of poly(dopamine): enabling protein resistance via
      short-chain ethylene oxide oligomers.
AB  - We present a facile strategy to modify poly(dopamine) (PDA)-coated substrates.
      Using thiol-terminated short chain ethylene oxide oligomers (OEG) under aqueous
      conditions, we explore the creation of a model surface exhibiting resistance to
      nonspecific protein absorption (RPA) by engineering the surface properties of a
      PDA adlayer. Surprisingly, dithiol-terminated OEG molecules demonstrated
      significantly greater coverage on PDA surfaces than analogous monothiol
      molecules. Successful RPA is only achieved with dithiol-terminated OEGs. 

PMID- 25774881
TI  - High-resolution postcontrast time-of-flight MR angiography of intracranial
      perforators at 7.0 Tesla.
AB  - BACKGROUND AND PURPOSE: Different studies already demonstrated the benefits of 7T
      for precontrast TOF-MRA in the visualization of intracranial small vessels. The
      aim of this study was to assess the performance of high-resolution 7T TOF-MRA
      after the administration of a gadolinium-based contrast agent in visualizing
      intracranial perforating arteries. MATERIALS AND METHODS: Ten consecutive
      patients (7 male; mean age, 50.4 +/- 9.9 years) who received TOF-MRA at 7T after
      contrast administration were retrospectively included in this study. Intracranial
      perforating arteries, branching from the parent arteries of the circle of Willis,
      were identified on all TOF-MRA images. Provided a TOF-MRA before contrast
      administration was present, a direct comparison between pre- and postcontrast TOF
      MRA was made. RESULTS: It was possible to visualize intracranial perforating
      arteries branching off from the entire circle of Willis, and their proximal
      branches. The posterior cerebral artery (P1 and proximal segment of P2) appeared
      to have the largest number of visible perforating branches (mean of 5.1 in each
      patient, with a range of 2-7). The basilar artery and middle cerebral artery (M1
      and proximal segment M2) followed with a mean number of 5.0 and 3.5 visible
      perforating branches (range of 1-9 and 1-8, respectively). Venous contamination
      in the postcontrast scans sometimes made it difficult to discern the arterial or
      venous nature of a vessel. CONCLUSION: High-resolution postcontrast TOF-MRA at 7T
      was able to visualize multiple intracranial perforators branching off from
      various parts of the circle of Willis and proximal intracranial arteries.
      Although confirmation in a larger study is needed, the administration of a
      contrast agent for high-resolution TOF-MRA at 7T seems to enable a better
      visualization of the distal segment of certain intracranial perforators.

PMID- 25774884
TI  - Maternal vitamin D deficiency during pregnancy elevates the risks of small for
      gestational age and low birth weight infants in Chinese population.
AB  - CONTEXT: Vitamin D deficiency is common in pregnant women. Nevertheless, the
      association between maternal vitamin D status during pregnancy and the risk of
      having small for gestational age (SGA) and low birth weight (LBW) infants is
      uncertain. OBJECTIVE: The objective of this study was to investigate whether
      there is a correlation between maternal vitamin D deficiency during pregnancy and
      the risk of having SGA and LBW infants in a Chinese population. DESIGN AND
      PARTICIPANTS: This was a population-based birth cohort study that recruited 3658
      eligible mother-and-singleton-offspring pairs. MAIN OUTCOME MEASURES: Serum 25
      hydroxyvitamin D was measured by RIA. The rate and relative risk (RR) for SGA and
      LBW infants were calculated among subjects with vitamin D deficiency and
      insufficiency during pregnancy. RESULTS: There was a positive correlation between
      maternal serum 25-hydroxyvitamin D level and offspring birth weight (r = 0.477; P
      < .001). Further analysis showed that 4.98% of neonates were LBW infants among
      the subjects with vitamin D deficiency (RR, 12.00; 95% confidence interval [CI],
      4.37, 33.00) and 1.32% among the subjects with vitamin D insufficiency (RR, 3.18;
      95% CI, 1.07, 9.48). After adjustment for confounders, the RR for LBW infants was
      12.31 (95% CI, 4.47, 33.89) among subjects with vitamin D deficiency and 3.15
      (95% CI, 1.06, 9.39) among subjects with vitamin D insufficiency. Moreover,
      16.01% of neonates were SGA infants among subjects with vitamin D deficiency (RR,
      5.72; 95% CI, 3.80, 8.59) and 5.59% among subjects with vitamin D insufficiency
      (RR, 1.99; 95% CI, 1.27, 3.13). After adjustment for confounders, the RR for SGA
      infants was 6.47 (95% CI, 4.30, 9.75) among subjects with vitamin D deficiency
      and 2.01 (95% CI, 1.28, 3.16) among subjects with vitamin D insufficiency.
      CONCLUSION: Maternal vitamin D deficiency during pregnancy elevates the risk of
      SGA and LBW infants in a Chinese population.

PMID- 25774883
TI  - Drug-induced exposure of Schistosoma mansoni antigens SmCD59a and SmKK7.
AB  - BACKGROUND: Schistosomiasis is a serious health problem especially in developing
      countries and affects more than 243 million people. Only few anthelmintic drugs
      are available up to now. A major obstacle for drug treatment is the different
      developmental stages and the varying host compartments during worm development.
      Anthelmintic drugs have been tested mainly on adult schistosomes or freshly
      transformed cercariae. Knowledge concerning the larval stages is lacking.
      METHODOLOGY/PRINCIPAL FINDINGS: In this study, we used in vitro-grown
      schistosomula (aged between 2 to 14 days) to investigate drug effects of the
      three anthelmintics praziquantel, artemether, and oxamniquine. Further, we
      analyzed the antibody accessibility of two exemplary schistosome antigens SmCD59a
      and SmKK7, before and after drug treatment. Our results demonstrated that
      praziquantel applied at a concentration of 1 MUM inhibited development of all
      life stages. Application of 10 MUM praziquantel led to dramatic morphological
      changes of all schistosomula. Artemether at 1 and 10 MUM had differential effects
      depending on whether it was applied to 2-day as compared to 7- and 14-day
      schistosomula. While 2-day schistosomula were not killed but inhibited from
      further development, severe morphological damage was seen in 7- and 14-day
      schistosomula. Oxamniquine (1 and 10 MUM) led to severe morphological impairment
      in all life stages. Analyzing the accessibility of the antigens SmCD59a and SmKK7
      before drug treatment showed no antibody binding on living intact schistosomula.
      However, when schistosomula were treated with anthelmintics, both antigens became
      exposed on the larvae. Oxamniquine turned out to be most effective in promoting
      antibody binding to all schistosomula stages. CONCLUSION: This study has revealed
      marked differences in anthelmintic drug effects against larvae. Drug treatment
      increases surface antigen presentation and renders larvae accessible to antibody
      attack.

PMID- 25774885
TI  - Homozygous loss-of-function mutations in SOHLH1 in patients with nonsyndromic
      hypergonadotropic hypogonadism.
AB  - CONTEXT: Hypergonadotropic hypogonadism presents in females with delayed or
      arrested puberty, primary or secondary amenorrhea due to gonadal dysfunction, and
      is further characterized by elevated gonadotropins and low sex steroids.
      Chromosomal aberrations and various specific gene defects can lead to
      hypergonadotropic hypogonadism. Responsible genes include those with roles in
      gonadal development or maintenance, sex steroid synthesis, or end-organ
      resistance to gonadotropins. Identification of novel causative genes in this
      disorder will contribute to our understanding of the regulation of human
      reproductive function. OBJECTIVES: The aim of this study was to identify and
      report the gene responsible for autosomal-recessive hypergonadotropic
      hypogonadism in two unrelated families. DESIGN AND PARTICIPANTS: Clinical
      evaluation and whole-exome sequencing were performed in two pairs of sisters with
      nonsyndromic hypergonadotropic hypogonadism from two unrelated families. RESULTS:
      Exome sequencing analysis revealed two different truncating mutations in the same
      gene: SOHLH1 c.705delT (p.Pro235fs*4) and SOHLH1 c.27C>G (p.Tyr9stop). Both
      mutations were unique to the families and segregation was consistent with
      Mendelian expectations for an autosomal-recessive mode of inheritance.
      CONCLUSIONS: Sohlh1 was known from previous mouse studies to be a transcriptional
      regulator that functions in the maintenance and survival of primordial ovarian
      follicles, but loss-of-function mutations in human females have not been
      reported. Our results provide evidence that homozygous-truncating mutations in
      SOHLH1 cause female nonsyndromic hypergonadotropic hypogonadism.

PMID- 25774887
TI  - Correction: Competing with lower level opponents decreases intra-team movement
      synchronization and time-motion demands during pre-season soccer matches.

PMID- 25774886
TI  - Interindividual variability in functional connectivity as long-term correlate of
      temporal discounting.
AB  - During intertemporal choice (IT) future outcomes are usually devaluated as a
      function of the delay, a phenomenon known as temporal discounting (TD). Based on
      task-evoked activity, previous neuroimaging studies have described several
      networks associated with TD. However, given its relevance for several disorders,
      a critical challenge is to define a specific neural marker able to predict TD
      independently of task execution. To this aim, we used resting-state functional
      connectivity MRI (fcMRI) and measured TD during economic choices several months
      apart in 25 human subjects. We further explored the relationship between TD,
      impulsivity and decision uncertainty by collecting standard questionnaires on
      individual trait/state differences. Our findings indicate that fcMRI within and
      between critical nodes of task-evoked neural networks associated with TD
      correlates with discounting behavior measured a long time afterwards,
      independently of impulsivity. Importantly, the nodes form an intrinsic circuit
      that might support all the mechanisms underlying TD, from the representation of
      subjective value to choice selection through modulatory effects of cognitive
      control and episodic prospection. 

PMID- 25774889
TI  - Towards a dosimetric framework for therapeutic ultrasound.
AB  - There is a need for a coherent set of exposure and dose quantities to describe
      ultrasound fields in media other than water (including tissue and tissue
      simulating materials). This paper proposes an outline dosimetry scheme, with
      quantities for free field exposure, in situ exposure, dose (both instantaneous
      and cumulative) and effect, to act as a structure for organising a more complete
      set of definitions. It also presents findings from a survey of the views of the
      therapeutic ultrasound community which generally supports the principle of using
      modified free field quantities to describe the in situ field, and the
      prioritising of dose quantities which are related to heating and thermal
      mechanisms. Although there is no one-to-one relationship between any known
      ultrasound dose quantity and a specific biological effect, this can also be said
      of radiotherapy and other modalities where weighting factors have been developed
      to calculate the degree of equivalence between different tissues and radiation
      types. This same separation is recommended for ultrasound, provided that an
      appropriate set of recognised 'engineering' quantities can be established for
      exposure and dose quantities. 

PMID- 25774888
TI  - Reemergence of enterovirus 71 epidemic in northern Taiwan, 2012.
AB  - BACKGROUND: Enterovirus 71 (EV71) belongs to picornavirus family and could be
      classified phylogenetically into three major genogroups (A, B and C) including 11
      genotypes (A, B1-B5 and C1-C5). Since 1997, EV71 has caused large-scale of
      epidemics with neurological complications in Asian children. In Taiwan,
      nationwide EV71 epidemics with different predominant genotypes have occurred
      cyclically since 1998. A nationwide EV71 epidemic occurred again in 2012. We
      conducted genetic and antigenic characterizations of the 2012 epidemic. METHODS:
      Chang Gung Memorial Hospital (CGMH) is a medical center in northern Taiwan. In
      CGMH, specimens were collected from pediatric inpatients with suspected
      enterovirus infections for virus isolation. Enterovirus isolates were serotyped
      and genotyped and sera from EV71 inpatients were collected for measuring
      neutralizing antibody titers. RESULTS: There were 10, 16 and 99 EV71 inpatients
      identified in 2010, 2011 and 2012, respectively. There were 82 EV71 isolates
      genotyped, which identified 17 genotype C4a viruses and 65 genotype B5 viruses.
      The genotype B5 viruses were not detected until November 2011 and caused
      epidemics in 2012. Interestingly, the B5-2011 viruses were genetically
      distinguishable from the B5 viruses causing the 2008 epidemic and are likely
      introduced from China or Southeastern Asia. Based on antigenic analysis, minor
      antigenic variations were detected among the B5-2008, B5-2011, C4a-2008 and C4a
      2012 viruses but these viruses antigenically differed from genotype A.
      CONCLUSIONS: Genotype B5 and C4a viruses antigenically differ from genotype A
      viruses which have disappeared globally for 30 years but have been detected in
      China since 2008. Enterovirus surveillance should monitor genetic and antigenic
      variations of EV71.

PMID- 25774890
TI  - A Patient With Word Blindness in the Seventeenth Century.
AB  - Johann Jakob Wepfer (1620-1695), city physician in Schaffhausen, Switzerland,
      published two books on "apoplexy." He proposed new ideas about the events in the
      brain during such attacks, based on Harvey's theory of the circulation of the
      blood. Wepfer postulated extravasation of whole blood or serum in the brain, in
      opposition to the Galenic notion of blocked ventricles. His case histories are
      remarkably precise and untainted by interpretation. This allows the recognition
      of a patient with word blindness, who was also unable to read words written by
      himself. Unlike patients with pure "alexia without agraphia," he could not write
      complete sentences because of additional language defects, especially speech
      comprehension. Jules Dejerine (1849-1917) would, in 1892, not only describe a
      patient with the pure form of this syndrome (cecite verbale avec integrite de
      l'ecriture spontanee et sous dictee) but also provide an explanation of its
      anatomical basis. 

PMID- 25774891
TI  - Addiction Treatment Professionals Are Not the Gatekeepers of Recovery.
AB  - Addiction treatment is beneficial to many individuals who have substance use
      disorders. However, only a minority of individuals who recover from addiction
      receive it. Despite this, addiction treatment is sometimes granted the status of
      the "gatekeeper of recovery." The myth that treatment is necessary for recovery
      has no empirical support. It also undermines the confidence of individuals in
      their ability to change on their own and is unduly dismissive of the efforts of
      nonprofessional helpers. 

PMID- 25774893
TI  - Understanding parental locus of control in Latino parents: Examination of
      cultural influences and help-seeking intentions for childhood ADHD.
AB  - OBJECTIVE: To address the disparities that exist in utilization of mental health
      services for ADHD among Latino families and to further our understanding of
      factors that influence parents' decisions to seek treatment for ADHD, the goal of
      the current study was to examine parental locus of control (PLOC) in a community
      sample of Latino parents. Specifically, the current study investigated cultural
      influences on PLOC, as well as the influence of PLOC on help-seeking. METHOD:
      Seventy-four primarily Spanish-speaking, Latino parents of school-age children
      completed measures to assess their help-seeking intentions, PLOC, and cultural
      orientation. RESULTS: Results indicated that U.S. mainstream orientation was
      associated with increased feelings of parental control and decreased beliefs in
      fate/chance and several Latino cultural values were associated with increased
      beliefs in fate/chance, and decreased feelings of parental efficacy and parental
      control. In addition, 2 PLOC domains (e.g., parental efficacy and fate/chance)
      were associated with beliefs that the behaviors of a child with ADHD would go
      away on their own. CONCLUSIONS: Results highlight the need for interventions
      aimed at modifying parenting behavior to take parents' cultural beliefs and
      values into account in order to accommodate and engage Latino families more
      effectively.

PMID- 25774892
TI  - Hypoxia-ischemia and therapeutic hypothermia in the neonatal mouse brain--a
      longitudinal study.

PMID- 25774894
TI  - Affect and understanding during everyday cross-race experiences.
AB  - The present research uses an event sampling method to test whether, compared to
      same-race interactions, everyday cross-race contact is better characterized by
      the presence of negative affect or the absence of positive affect. Everyday
      intergroup interactions have some positive and negative aspects, so the present
      research independently assesses positive affect and negative affect along with
      felt understanding and misunderstanding. Across 3 studies (Study 1, n = 107;
      Study 2, n = 112; Study 3, n = 146), we find that European, Asian, and African
      Americans report that everyday cross-race interactions generate less positive
      affect and felt understanding than same-race interactions. Yet cross-race
      interactions entail no more negative affect than same-race interactions. This
      supports the idea that positive emotions are mostly reserved for and experienced
      with the ingroup, rather than the idea that people feel animosity toward the
      outgroup. Given that nearly half of racial-minority group member's everyday
      interactions are cross-race, their daily encounters are typically less positive
      than those of racial-majority group members. Feeling less well understood as a
      result of cross-race contact may increase the likelihood that racial-minority
      group members question whether they belong on a college campus.

PMID- 25774895
TI  - Maori identity signatures: A latent profile analysis of the types of Maori
      identity.
AB  - Maori are the indigenous peoples of New Zealand. However, the term 'Maori' can
      refer to a wide range of people of varying ethnic compositions and cultural
      identity. We present a statistical model identifying 6 distinct types, or 'Maori
      Identity Signatures,' and estimate their proportion in the Maori population. The
      model is tested using a Latent Profile Analysis of a national probability sample
      of 686 Maori drawn from the New Zealand Attitudes and Values Study. We identify 6
      distinct signatures: Traditional Essentialists (22.6%), Traditional Inclusives
      (16%), High Moderates (31.7%), Low Moderates (18.7%), Spiritually Orientated
      (4.1%), and Disassociated (6.9%). These distinct Identity Signatures predicted
      variation in deprivation, age, mixed-ethnic affiliation, and religion. This
      research presents the first formal statistical model assessing how people's
      identity as Maori is psychologically structured, documents the relative
      proportion of these different patterns of structures, and shows that these
      patterns reliably predict differences in core demographics. We identify a range
      of patterns of Maori identity far more diverse than has been previously proposed
      based on qualitative data, and also show that the majority of Maori fit a
      moderate or traditional identity pattern. The application of our model for
      studying Maori health and identity development is discussed.

PMID- 25774896
TI  - Hidden consequences of political efficacy: Testing an efficacy-apathy model of
      political mobilization.
AB  - Political efficacy-the belief that one can influence politics-is a key predictor
      of people's involvement in social movements. Political institutions that are open
      to change should, however, be seen as just. Thus, political efficacy may
      ironically undermine minority group members' support for collective action by
      simultaneously increasing their belief in the fairness of the system. The current
      study aims to examine this possibility in a national sample of Maori-New
      Zealand's indigenous minority population. Participants (N = 399) were Maori (Mage
      = 44.22; SD = 13.30) women (n = 272) and men (n = 115; unreported = 12) who
      completed a survey assessing their levels of (a) political efficacy, (b) system
      justification, and (c) support for the political mobilization of their group, as
      well as relevant demographic covariates. Consistent with past research, political
      efficacy had a positive direct effect on participants' support for the political
      mobilization of Maori. Nevertheless, political efficacy also had a negative
      indirect effect on political mobilization support via increases in system
      justification. These results held after controlling for participants' ethnic
      identification, self-efficacy, and conservatism. Our findings uncover a hidden
      consequence of political efficacy and show that, while believing that the
      political system is receptive to change predicts political mobilization, it can
      also undermine minorities' support for the mobilization of their group. Thus, our
      results uncover a previously unknown process that maintains inequality between
      ethnic minority and majority group members.

PMID- 25774897
TI  - Culture and risk assessments: Why Latino Americans perceive greater risk for
      diabetes.
AB  - OBJECTIVE: Large ethnic disparities exist in health outcomes, yet little is known
      about the psychological mechanisms that underlie these differences. We propose
      that a key to understanding ethnic minority health is to recognize the cultural
      factors that influence perceived vulnerability to disease (PVD), specifically
      ethnicity and ethnic identification. In 3 studies, we examined how these cultural
      factors were associated with PVD to Type II diabetes, a highly prevalent disease
      among Latino Americans. We had 3 specific aims. The first was to examine ethnic
      group differences in PVD between European Americans and Latino Americans. The
      second was to examine potential psychological mechanisms that account for ethnic
      differences in PVD. The third was to examine the relationship between ethnic
      identification and PVD among Latino Americans. METHOD: Participants in all
      studies were young European American and Latino American adults and were from
      independent samples. In all 3 studies, participants completed the questionnaires
      online. RESULTS: Study 1 found that Latino Americans as compared with European
      Americans have higher PVD to diabetes. Study 2 showed that perceived similarity
      to the typical person who gets diabetes and the number of reported family members
      with diabetes predicted the degree of PVD to diabetes. However, we found that the
      nature of the associations between these mechanisms and perceived risk differed
      by ethnic group. Study 3 examined what may be influencing perceived similarity
      for Latino Americans; we found ethnic identification is a significant factor.
      DISCUSSION: Together, the present findings have broad implications for diabetes
      communication, education, and health campaigns.

PMID- 25774898
TI  - "What are you?" Multiracial individuals' responses to racial identification
      inquiries.
AB  - OBJECTIVES: Guided by a racial microaggression framework and utilizing a mixed
      method approach, this study explores multiracial individuals' interpersonal
      experiences and perceptions of racial identification inquiries--queries directed
      toward them as others attempt to determine their racial background (e.g., "What
      are you?"). METHODS: As part of an online study, multiracial college students (n
      = 40) were presented with a hypothetical situation in which racial identification
      inquiries were delivered by a White, racial minority, or racially unspecified
      communicator. Qualitative analyses identified the categories and thematic codes
      of participants' open-ended explanations of the personal relevance of these
      hypothetical situations and proposed endings. Nonparametric tests examined
      differences in situation, affect, and communication partner ratings based on race
      of the communicator. RESULTS: Findings affirmed that racial identification
      inquiries are commonly reported by diverse multiracial individuals (92.5% of the
      present sample). Qualitative coding of participants' explanations of personal
      relevance and proposed endings for the hypothetical situations, as well as
      ratings of situation, affect, and communication partner, revealed both positive
      and negative characterizations ascribed to racial identification inquiry
      experiences. Participants who imagined the queries came from a White communicator
      allotted less time to continuing the conversation than those in the control
      condition (communicator race unspecified). CONCLUSIONS: A racial microaggression
      framework was relevant but not sufficient in reflecting the complex nature of
      racial identification inquiries for multiracial individuals. The insights into
      multiracial individuals' perceptions of these stimuli encourage more critical and
      dynamic thinking about racial categorization systems and interpersonal racial
      processes for this underrepresented but growing population.

PMID- 25774899
TI  - Contributions of acculturation, enculturation, discrimination, and personality
      traits to social anxiety among Chinese immigrants: A context-specific assessment.
AB  - Based on the diathesis-stress model of anxiety, this study examined the
      contributions of cultural processes, perceived racial discrimination, and
      personality traits to social anxiety among Chinese immigrants. Further guided by
      the theory of intergroup anxiety, this study also adopted a context-specific
      approach to distinguish between participants' experience of social anxiety when
      interacting with European Americans versus with other Chinese in the United
      States. This quantitative and ex post facto study used a convenience sample of
      140 first-generation Chinese immigrants. Participants were recruited through e
      mails from different university and community groups across the United States.
      The sample includes 55 men and 82 women (3 did not specify) with an average age
      of 36 years old. Results showed that more social anxiety was reported in the
      European American context than in the Chinese ethnic context. The full models
      accounted for almost half the variance in anxiety in each context. Although
      personality accounted for the most variance, the cultural variables and
      discrimination contributed 14% of the unique variance in the European American
      context. Notably, low acculturation, high neuroticism, and low extraversion were
      unique contributors to social anxiety with European Americans, whereas in the
      Chinese ethnic context only low extraversion was a unique contributor; more
      discrimination was uniquely significant in both contexts. The findings suggest a
      need to contextualize the research and clinical assessment of social anxiety, and
      have implications for culturally sensitive counseling with immigrants.

PMID- 25774900
TI  - Correction: palmitate activates autophagy in INS-1E beta-cells and in isolated
      rat and human pancreatic islets.

PMID- 25774901
TI  - Holocellulose nanocrystals: amphiphilicity, oil/water emulsion, and self
      assembly.
AB  - Amphiphilic holoCNCs were derived from rice straw holocellulose by sulfuric acid
      hydrolysis (64%, 45  degrees C, 45 min) at 11.6% yield (8.8% of rice straw).
      HoloCNCs are similar in lateral dimensions (4.1 +/- 1.6 nm thick, 6.4 +/- 1.8 nm
      wide), but shorter and more heterogeneous in lengths (113 +/- 70 nm long), less
      negatively charged (0.128 mmol/g) and less crystalline (CrI 84.4%) than CNCs.
      HoloCNCs were also more thermally stable (Tmax =284  degrees C), attributed to
      the presence of residual lignosulfonate, hemicellulose, and silica. Most
      remarkable, the amphiphilic holoCNCs were more hydrophobic than CNCs, exhibiting
      distinct surface active behaviors and lowering equilibrium surface tension to
      49.2 mN/m at above 0.57% critical aggregation concentration. HoloCNCs not only
      stabilize 30% more oil-in-water (O/W) emulsion and formed droplets (1.2-1.6 MUm)
      doubled the sizes of those with CNCs, but also self-assembled into highly
      mesoporous structures with up to 3* higher specific surface (111 m(2)/g) and
      total pore volume (0.40 cm(3)/g) than that from CNCs upon freeze-drying. The
      unique surface active, amphiphilic, and less self-assembling properties of
      holoCNCs offer new desirable characteristics but without additional isolation
      process nor surface modification of CNCs. 

PMID- 25774902
TI  - Beyond local group modes in vibrational sum frequency generation.
AB  - We combine deuterium labeling, density functional theory calculations, and
      experimental vibrational sum frequency generation spectroscopy into a form of
      "counterfactual-enabled molecular spectroscopy" for producing reliable
      vibrational mode assignments in situations where local group mode approximations
      are insufficient for spectral interpretation and vibrational mode assignments. We
      demonstrate the method using trans-beta-isoprene epoxydiol (trans-beta-IEPOX), a
      first-generation product of isoprene relevant to atmospheric aerosol formation,
      and one of its deuterium-labeled isotopologues at the vapor/silica interface. We
      use our method to determine that the SFG responses that we obtain from trans-beta
      IEPOX are almost exclusively due to nonlocal modes involving multiple C-H groups
      oscillating at the same frequency as one vibrational mode. We verify our
      assignments using deuterium labeling and use DFT calculations to predict SFG
      spectra of additional isotopologues that have not yet been synthesized. Finally,
      we use our new insight to provide a viable alternative to molecular orientation
      analysis methods that rely on local mode approximations in cases where the local
      mode approximation is not applicable. 

PMID- 25774903
TI  - Fingolimod prevents blood-brain barrier disruption induced by the sera from
      patients with multiple sclerosis.
AB  - OBJECTIVE: Effect of fingolimod in multiple sclerosis (MS) is thought to involve
      the prevention of lymphocyte egress from lymphoid tissues, thereby reducing
      autoaggressive lymphocyte infiltration into the central nervous system across
      blood-brain barrier (BBB). However, brain microvascular endothelial cells (BMECs)
      represent a possible additional target for fingolimod in MS patients by directly
      repairing the function of BBB, as S1P receptors are also expressed by BMECs. In
      this study, we evaluated the effects of fingolimod on BMECs and clarified whether
      fingolimod-phosphate restores the BBB function after exposure to MS sera.
      METHODS: Changes in tight junction proteins, adhesion molecules and
      transendothelial electrical resistance (TEER) in BMECs were evaluated following
      incubation in conditioned medium with or without fingolimod/fingolimod-phosphate.
      In addition, the effects of sera derived from MS patients, including those in the
      relapse phase of relapse-remitting (RR) MS, stable phase of RRMS and secondary
      progressive MS (SPMS), on the function of BBB in the presence of fingolimod
      phosphate were assessed. RESULTS: Incubation with fingolimod-phosphate increased
      the claudin-5 protein levels and TEER values in BMECs, although it did not change
      the amount of occludin, ICAM-1 or MelCAM proteins. Pretreatment with fingolimod
      phosphate restored the changes in the claudin-5 and VCAM-1 protein/mRNA levels
      and TEER values in BMECs after exposure to MS sera. CONCLUSIONS: Pretreatment
      with fingolimod-phosphate prevents BBB disruption caused by both RRMS and SPMS
      sera via the upregulation of claudin-5 and downregulation of VCAM-1 in BMECs,
      suggesting that fingolimod-phosphate is capable of directly modifying the BBB.
      BMECs represent a possible therapeutic target for fingolimod in MS patients.

PMID- 25774904
TI  - Identification of a novel reference gene for apple transcriptional profiling
      under postharvest conditions.
AB  - Reverse Transcription quantitative PCR (RT-qPCR) is one of the most important
      techniques for gene expression profiling due to its high sensibility and
      reproducibility. However, the reliability of the results is highly dependent on
      data normalization, performed by comparisons between the expression profiles of
      the genes of interest against those of constitutively expressed, reference genes.
      Although the technique is widely used in fruit postharvest experiments, the
      transcription stability of reference genes has not been thoroughly investigated
      under these experimental conditions. Thus, we have determined the transcriptional
      profile, under these conditions, of three genes commonly used as reference--ACTIN
      (MdACT), PROTEIN DISULPHIDE ISOMERASE (MdPDI) and UBIQUITIN-CONJUGATING ENZYME E2
      (MdUBC)--along with two novel candidates--HISTONE 1 (MdH1) and NUCLEOSSOME
      ASSEMBLY 1 PROTEIN (MdNAP1). The expression profile of the genes was investigated
      throughout five experiments, with three of them encompassing the postharvest
      period and the other two, consisting of developmental and spatial phases. The
      transcriptional stability was comparatively investigated using four distinct
      software packages: BestKeeper, NormFinder, geNorm and DataAssist. Gene ranking
      results for transcriptional stability were similar for the investigated software
      packages, with the exception of BestKeeper. The classic reference gene MdUBC
      ranked among the most stably transcribed in all investigated experimental
      conditions. Transcript accumulation profiles for the novel reference candidate
      gene MdH1 were stable throughout the tested conditions, especially in experiments
      encompassing the postharvest period. Thus, our results present a novel reference
      gene for postharvest experiments in apple and reinforce the importance of
      checking the transcription profile of reference genes under the experimental
      conditions of interest.

PMID- 25774905
TI  - Molybdenum carbide nanocatalysts at work in the in situ environment: a density
      functional tight-binding and quantum mechanical/molecular mechanical study.
AB  - Heterogeneous reactions catalyzed by transition-metal-containing nanoparticles
      represent a crucial type of reaction in chemical industry. Because of the
      existing gap in understanding heterogeneous catalysis between a cluster of a few
      atoms and a bulk model of periodic slabs, reactions catalyzed by transition-metal
      containing nanoparticles are still not well understood. Herein, we provide a
      multiscale modeling approach to study the benzene hydrogenation reactions on
      molybdenum carbide nanoparticles (MCNPs) in the process of in situ heavy oil
      upgrading. By coupling the quantum mechanical (QM) density functional tight
      binding (DFTB) method with a molecular mechanical (MM) force field, a QM/MM model
      was built to describe the reactants, the nanoparticles and the surroundings.
      Umbrella sampling (US) was used to calculate the free energy profiles of the
      benzene hydrogenation reactions in a model aromatic solvent in the in situ heavy
      oil upgrading conditions. By comparing with the traditional method in
      computational heterogeneous catalysis, the results reveal new features of the
      metallic MCNPs. Rather than being rigid, they are very flexible under working
      condition due to the entropic contributions of the MCNPs and the solvent, which
      greatly affect the free energy profiles of these nanoscale heterogeneous
      reactions. 

PMID- 25774906
TI  - Identification of OmpR-family response regulators interacting with thioredoxin in
      the Cyanobacterium Synechocystis sp. PCC 6803.
AB  - The redox state of the photosynthetic electron transport chain is known to act as
      a signal to regulate the transcription of key genes involved in the acclimation
      responses to environmental changes. We hypothesized that the protein thioredoxin
      (Trx) acts as a mediator connecting the redox state of the photosynthetic
      electron transport chain and transcriptional regulation, and established a
      screening system to identify transcription factors (TFs) that interact with Trx.
      His-tagged TFs and S-tagged mutated form of Trx, TrxMC35S, whose active site
      cysteine 35 was substituted with serine to trap the target interacting protein,
      were co-expressed in E. coli cells and Trx-TF complexes were detected by immuno
      blotting analysis. We examined the interaction between Trx and ten OmpR family
      TFs encoded in the chromosome of the cyanobacterium Synechocystis sp. PCC 6803
      (S.6803). Although there is a highly conserved cysteine residue in the receiver
      domain of all OmpR family TFs, only three, RpaA (Slr0115), RpaB (Slr0947) and
      ManR (Slr1837), were identified as putative Trx targets [corrected].The
      recombinant forms of wild-type TrxM, RpaA, RpaB and ManR proteins from S.6803
      were purified following over-expression in E. coli and their interaction was
      further assessed by monitoring changes in the number of cysteine residues with
      free thiol groups. An increase in the number of free thiols was observed after
      incubation of the oxidized TFs with Trx, indicating the reduction of cysteine
      residues as a consequence of interaction with Trx. Our results suggest, for the
      first time, the possible regulation of OmpR family TFs through the supply of
      reducing equivalents from Trx, as well as through the phospho-transfer from its
      cognate sensor histidine kinase.

PMID- 25774908
TI  - Cu(In,Ga)(S,Se)2 thin film solar cell with 10.7% conversion efficiency obtained
      by selenization of the Na-doped spray-pyrolyzed sulfide precursor film.
AB  - Selenium-rich Cu(In,Ga)(S,Se)2 (CIGSSe) thin films on an Mo-coated soda-lime
      glass substrate were fabricated by spray pyrolysis of an aqueous precursor
      solution containing Cu(NO3)2, In(NO3)3, Ga(NO3)3, and thiourea followed by
      selenization at 560  degrees C for 10 min. We studied the effects of intentional
      sodium addition on the structural and morphological properties of the fabricated
      CIGSSe films by dissolving NaNO3 in the aqueous precursor solution. The addition
      of sodium was found to affect the morphology of the final CIGSSe film: the film
      had denser morphology than that of the CIGSSe film obtained without addition of
      NaNO3. Photoelectrochemical measurements also revealed that the acceptor density
      of the nondoped CIGSSe film was relatively high (N(a) = 7.2 * 10(17) cm(-3)) and
      the addition of sodium led to a more favorable value for solar cell application
      (N(a) = 1.8 * 10(17) cm(-3)). As a result, a solar cell based on the sodium
      modified CIGSSe film exhibited maximum conversion efficiency of 8.8%, which was
      significantly higher than that of the cell based on nondoped CIGSSe (4.4%). In
      addition, by applying MgF2 antireflection coating to the device, the maximum
      efficiency was further improved to 10.7%.

PMID- 25774907
TI  - Non-protein coding RNA genes as the novel diagnostic markers for the
      discrimination of Salmonella species using PCR.
AB  - Salmonellosis, a communicable disease caused by members of the Salmonella
      species, transmitted to humans through contaminated food or water. It is of
      paramount importance, to generate accurate detection methods for discriminating
      the various Salmonella species that cause severe infection in humans, including
      S. Typhi and S. Paratyphi A. Here, we formulated a strategy of detection and
      differentiation of salmonellosis by a multiplex polymerase chain reaction assay
      using S. Typhi non-protein coding RNA (sRNA) genes. With the designed sequences
      that specifically detect sRNA genes from S. Typhi and S. Paratyphi A, a detection
      limit of up to 10 pg was achieved. Moreover, in a stool-seeding experiment with
      S. Typhi and S. Paratyphi A, we have attained a respective detection limit of 15
      and 1.5 CFU/mL. The designed strategy using sRNA genes shown here is
      comparatively sensitive and specific, suitable for clinical diagnosis and disease
      surveillance, and sRNAs represent an excellent molecular target for infectious
      disease. 

PMID- 25774909
TI  - Improved climate risk simulations for rice in arid environments.
AB  - We integrated recent research on cardinal temperatures for phenology and early
      leaf growth, spikelet formation, early morning flowering, transpirational
      cooling, and heat- and cold-induced sterility into an existing to crop growth
      model ORYZA2000. We compared for an arid environment observed potential yields
      with yields simulated with default ORYZA2000, with modified subversions of
      ORYZA2000 and with ORYZA_S, a model developed for the region of interest in the
      1990s. Rice variety 'IR64' was sown monthly 15-times in a row in two locations in
      Senegal. The Senegal River Valley is located in the Sahel, near the Sahara desert
      with extreme temperatures during day and night. The existing subroutines
      underestimated cold stress and overestimated heat stress. Forcing the model to
      use observed spikelet number and phenology and replacing the existing heat and
      cold subroutines improved accuracy of yield simulation from EF = -0.32 to EF
      =0.70 (EF is modelling efficiency). The main causes of improved accuracy were
      that the new model subversions take into account transpirational cooling (which
      is high in arid environments) and early morning flowering for heat sterility, and
      minimum rather than average temperature for cold sterility. Simulations were less
      accurate when also spikelet number and phenology were simulated. Model efficiency
      was 0.14 with new heat and cold routines and improved to 0.48 when using new
      cardinal temperatures for phenology and early leaf growth. The new adapted
      subversion of ORYZA2000 offers a powerful analytic tool for climate change impact
      assessment and cropping calendar optimisation in arid regions. 

PMID- 25774910
TI  - Detection of reactive metabolites using isotope-labeled glutathione trapping and
      simultaneous neutral loss and precursor ion scanning with ultra-high-pressure
      liquid chromatography triple quadruple mass spectrometry.
AB  - Metabolic activation of drugs to electrophilic species is responsible for over
      60% of black box warnings and drug withdrawals from the market place in the
      United States. Reactive metabolite trapping using glutathione (GSH) and analysis
      using high-performance liquid chromatography-tandem mass spectrometry (HPLC
      MS/MS) or HPLC with high resolution mass spectrometry (mass defect filtering)
      have enabled screening for metabolic activation to become routine during drug
      development. However, current MS-based approaches cannot detect all GSH
      conjugates present in complex mixtures, especially those present in extracts of
      botanical dietary supplements. To overcome these limitations, a fast triple
      quadrupole mass spectrometer-based approach was developed that can detect
      positively and negatively charged GSH conjugates in a single analysis without the
      need for advanced knowledge of the elemental compositions of potential conjugates
      and while avoiding false positives. This approach utilized UHPLC instead of HPLC
      to shorten separation time and enhance sensitivity, incorporated stable-isotope
      labeled GSH to avoid false positives, and used fast polarity switching
      electrospray MS/MS to detect GSH conjugates that form positive and/or negative
      ions. The general new method was then used to test the licorice dietary
      supplement Glycyrrhiza glabra, which was found to form multiple GSH conjugates
      upon metabolic activation. Among the GSH conjugates found in the licorice assay
      were conjugates with isoliquiritigenin and glabridin, which is an irreversible
      inhibitor of cytochrome P450 enzymes. 

PMID- 25774913
TI  - A simple mechanistic model to interpret the effects of narcotics.
AB  - In this research we will show the advantages of using a time-independent dose
      metric in a mechanistic model to evaluate toxic effects for different narcotic
      compounds on different species. We will show how different already existing QSARs
      can be combined within a mechanistic framework to 1) make predictions of lethal
      thresholds; 2) show some limitations in the use of existing QSARs; 3) show how a
      mechanistic framework solves some conceptual problems in current approaches and
      4) show how such a framework can be used to be of aid in an experimental setup in
      predicting the outcome of a survival experiment. The approach we chose is based
      on the simplest mechanistic model available, a scaled one-compartment model to
      describe uptake and elimination and hazard model to link the exposure to effects
      on survival. Within this theoretical framework a prediction for an internal
      threshold for effects on survival of 3 mmol/kg bw can be made, which should be
      similar for different species and independent of the partitioning characteristics
      of the toxicant. To demonstrate this, a threshold for 51 different species was
      derived, which indeed appeared to lie in a relatively small range, typically
      between 1 and 10 mmol/kg bw. 

PMID- 25774911
TI  - Echocardiographic predictors of mortality in patients with pulmonary hypertension
      and cardiopulmonary comorbidities.
AB  - OBJECTIVE: We aimed to identify the echocardiographic measures associated with
      survival in a patient population with a high prevalence of co-morbid
      cardiovascular and pulmonary disease that have significantly elevated estimated
      pulmonary artery systolic pressures (ePASP). BACKGROUND: Pulmonary hypertension
      (PH) is a clinical feature of several cardiopulmonary diseases that are prevalent
      among elderly. While certain echocardiographic parameters have been shown to be
      important in the prognosis in specific PH groups, the prognostic relevance of
      echocardiographic characteristics in a cohort with multiple cardiopulmonary
      comorbidities is unclear. METHODS: We retrospectively identified 152 patients
      with ePASP > 60 mmHg by echocardiography over a five year period (6/2006-11/2011)
      and followed until 4/2013. Candidate clinical and echocardiographic
      characteristics suggestive of PH severity were compared between deceased and
      surviving subpopulations. Cox proportional hazard modeling was used to identify
      echocardiographic predictors of death adjusted for age and clinical
      characteristics. RESULTS: This was a predominantly elderly (age 78.8 +/- 10.2
      years), male (98.7%) cohort with several cardiopulmonary comorbidities. Overall
      mortality was high (69.7%, median survival 129 days). After adjusting for age and
      clinical characteristics, decreased right ventricular (RV) systolic function
      assessed by tricuspid annular plane systolic excursion (HR 0.56, 95% CI 0.33
      0.96, p = 0.034) and increased RV thickness (HR: 4.34, 95% CI: 1.49-12.59, p =
      0.007) were independently associated with mortality. In contrast, left
      ventricular systolic function, left ventricular diastolic parameters, ePASP, or
      echo-derived pulmonary vascular resistance (PVR) were not associated with
      increased mortality. CONCLUSION: In a cohort of patients with PH and high
      prevalence of cardio-pulmonary comorbidities, RV systolic function and
      hypertrophy are associated with mortality and may be the most relevant
      echocardiographic markers for prognosis.

PMID- 25774912
TI  - Protein expression of DNA damage repair proteins dictates response to
      topoisomerase and PARP inhibitors in triple-negative breast cancer.
AB  - Patients with metastatic triple-negative breast cancer (TNBC) have a poor
      prognosis. New approaches for the treatment of TNBC are needed to improve patient
      survival. The concept of synthetic lethality, brought about by inactivating
      complementary DNA repair pathways, has been proposed as a promising therapeutic
      option for these tumors. The TNBC tumor type has been associated with BRCA
      mutations, and inhibitors of Poly (ADP-ribose) polymerase (PARP), a family of
      proteins that facilitates DNA repair, have been shown to effectively kill BRCA
      defective tumors by preventing cells from repairing DNA damage, leading to a loss
      of cell viability and clonogenic survival. Here we present preclinical efficacy
      results of combining the PARP inhibitor, ABT-888, with CPT-11, a topoisomerase I
      inhibitor. CPT-11 binds to topoisomerase I at the replication fork, creating a
      bulky adduct that is recognized as damaged DNA. When DNA damage was stimulated
      with CPT-11, protein expression of the nucleotide excision repair enzyme ERCC1
      inversely correlated with cell viability, but not clonogenic survival. However, 4
      out of the 6 TNBC cells were synergistically responsive by cell viability and 5
      out of the 6 TNBC cells were synergistically responsive by clonogenic survival to
      the combination of ABT-888 and CPT-11. In vivo, the BRCA mutant cell line MX-1
      treated with CPT-11 alone demonstrated significant decreased tumor growth; this
      decrease was enhanced further with the addition of ABT-888. Decrease in tumor
      growth correlated with an increase in double strand DNA breaks as measured by
      gamma-H2AX phosphorylation. In summary, inhibiting two arms of the DNA repair
      pathway simultaneously in TNBC cell lines, independent of BRCA mutation status,
      resulted in un-repairable DNA damage and subsequent cell death. 

PMID- 25774914
TI  - Yy1 gene dosage effect and bi-allelic expression of Peg3.
AB  - In the current study, we tested the in vivo effects of Yy1 gene dosage on the
      Peg3 imprinted domain with various breeding schemes utilizing two sets of mutant
      alleles. The results indicated that a half dosage of Yy1 coincides with the up
      regulation of Peg3 and Zim1, suggesting a repressor role of Yy1 in this imprinted
      domain. This repressor role of Yy1 is consistent with the observations derived
      from previous in vitro studies. The current study also provided an unexpected
      observation that the maternal allele of Peg3 is also normally expressed, and thus
      the expression of Peg3 is bi-allelic in the specific areas of the brain,
      including the choroid plexus, the PVN (Paraventricular Nucleus) and the SON
      (Supraoptic Nucleus) of the hypothalamus. The exact roles of the maternal allele
      of Peg3 in these cell types are currently unknown, but this new finding confirms
      the previous prediction that the maternal allele may be functional in specific
      cell types based on the lethality associated with the homozygotes for several
      mutant alleles of the Peg3 locus. Overall, these results confirm the repressor
      role of Yy1 in the Peg3 domain and also provide a new insight regarding the bi
      allelic expression of Peg3 in mouse brain. 

PMID- 25774917
TI  - Interfacial nondegenerate doping of MoS2 and other two-dimensional
      semiconductors.
AB  - Controlled nondegenerate doping of two-dimensional semiconductors (2DSs) with
      their ultraconfined carriers, high quantum capacitance, and surface-sensitive
      electronics can enable tuning their Fermi levels for rational device design.
      However, doping techniques for three-dimensional semiconductors, such as ion
      implantation, cannot be directly applied to 2DSs because they inflict high defect
      density. In this issue of ACS Nano, Park et al. demonstrate that interfacing 2DSs
      with substrates having dopants can controllably inject carriers to achieve
      nondegenerate doping, thus significantly broadening 2DSs' functionality and
      applications. Futuristically, this can enable complex spatial
      patterning/contouring of energy levels in 2DSs to form p-n junctions, integrated
      logic, and opto/electronic devices. The process is also extendable to biocellular
      interfaced devices, band-continuum structures, and intricate 2D circuitry. 

PMID- 25774916
TI  - Osteocytic protein expression response to doxercalciferol therapy in pediatric
      dialysis patients.
AB  - BACKGROUND: Osteocytic protein expression is dysregulated in CKD and is affected
      by changes in mineral metabolism; however the effects of active vitamin D sterol
      therapy on osteocyte protein expression in advanced CKD is unknown. METHODS:
      Eleven pediatric patients with end stage kidney disease underwent bone biopsy,
      were treated for 8 months with doxercalciferol, and then underwent a second bone
      biopsy. Bone expression of fibroblast growth factor 23 (FGF23), dentin matrix
      protein 1 (DMP1), and sclerostin were determined by immunohistochemistry and
      quantified by Ariol Scanning. Western blot analysis and qRT-PCR was performed on
      bone abstracts of a subset of study subjects to determine the nature (i.e. size)
      of FGF23 and DMP1 in bone before and after therapy. RESULTS: As assessed by
      immunohistochemistry, bone FGF23, DMP1 and sclerostin protein all increased with
      therapy. In the case of FGF23, this increase was due to an increase in the full
      length molecule without the appearance of FGF23 fragments. DMP1 was present
      primarily in its full-length form in healthy controls while 57kDa and 37kDa
      fragments of DMP1 were apparent in bone of dialysis patients at baseline and the
      57 kDa appeared to decrease with therapy. CONCLUSION: Marked changes in
      osteocytic protein expression accompany doxercalciferol therapy, potentially
      impacting bone mineralization and the skeletal response to PTH. The effects of
      these bone changes on long-term outcomes remain to be determined.

PMID- 25774915
TI  - DNA barcoding of Rhodiola (crassulaceae): a case study on a group of recently
      diversified medicinal plants from the Qinghai-Tibetan Plateau.
AB  - DNA barcoding, the identification of species using one or a few short
      standardized DNA sequences, is an important complement to traditional taxonomy.
      However, there are particular challenges for barcoding plants, especially for
      species with complex evolutionary histories. We herein evaluated the utility of
      five candidate sequences - rbcL, matK, trnH-psbA, trnL-F and the internal
      transcribed spacer (ITS) - for barcoding Rhodiola species, a group of high
      altitude plants frequently used as adaptogens, hemostatics and tonics in
      traditional Tibetan medicine. Rhodiola was suggested to have diversified rapidly
      recently. The genus is thus a good model for testing DNA barcoding strategies for
      recently diversified medicinal plants. This study analyzed 189 accessions,
      representing 47 of the 55 recognized Rhodiola species in the Flora of China
      treatment. Based on intraspecific and interspecific divergence and degree of
      monophyly statistics, ITS was the best single-locus barcode, resolving 66% of the
      Rhodiola species. The core combination rbcL+matK resolved only 40.4% of them.
      Unsurprisingly, the combined use of all five loci provided the highest
      discrimination power, resolving 80.9% of the species. However, this is weaker
      than the discrimination power generally reported in barcoding studies of other
      plant taxa. The observed complications may be due to the recent diversification,
      incomplete lineage sorting and reticulate evolution of the genus. These processes
      are common features of numerous plant groups in the high-altitude regions of the
      Qinghai-Tibetan Plateau. 

PMID- 25774918
TI  - COL9A1 gene polymorphism is associated with Kashin-Beck disease in a northwest
      Chinese Han population.
AB  - OBJECTIVE: We sought to determine whether genomic polymorphism in collagen IX
      genes (COL9A) was associated with Kashin-Beck disease (KBD). METHODS: Twenty
      seven single nucleotide polymorphisms (SNPs) in COL9AI, COL9A2 and COL9A3 were
      genotyped in 274 KBD cases and 248 healthy controls using the Sequenom MassARRAY
      system. Associations between the COL9A polymorphism and KBD risk were detected
      using an unconditional logistic regression model. Linkage disequilibrium (LD) and
      haplotypes analysis were performed with the Haploview software. RESULTS: After
      Bonferroni correction, the frequency distribution of genotypes in rs6910140 in
      COL9A1 was significantly different between the KBD and the control groups (X2 =
      16.74, df = 2, P = 0.0002). Regression analysis showed that the allele "C" in SNP
      rs6910140 had a significant protective effect on KBD [odds ratio (OR) = 0.49, 95%
      confidence interval (CI) = 0.34-0.70, P = 0.0001]. The frequencies of alleles and
      genotypes in rs6910140 were significantly different among subjects of different
      KBD stages (allele: X2 = 7.82, df = 2, P = 0.02, genotype: X2 = 14.81, df = 4, P
      = 0.005). However, haplotype analysis did not detect any significant association
      between KBD and COL9A1, COL9A2 and COL9A3. CONCLUSIONS: We observed a significant
      association between rs6910140 of COL9A1 and KBD, suggesting a role of COL9A1 in
      the development of KBD.

PMID- 25774919
TI  - Drug Sales, Gender, and Risk: Notions of Risk From the Perspective of Gang
      Involved Young Adults.
AB  - We examine gender and meanings of risk in interviews (2007-2010) with gang
      involved young men and women (n = 253) engaged in illicit drug sales in San
      Francisco, California. The in-depth interviews from this NIDA-funded study were
      coded using the software NVivo to identify patterns and themes. We examine their
      interpretations of the risks of drug-selling and their narratives about gender
      differences in these risks. We find distinct discourses regarding the role of
      femininities and masculinities and male and female bodies in shaping risk as well
      as the nexus between gender, family, and risk for female drug sellers. 

PMID- 25774920
TI  - A conserved NS3 surface patch orchestrates NS2 protease stimulation, NS5A
      hyperphosphorylation and HCV genome replication.
AB  - Hepatitis C virus (HCV) infection is a leading cause of liver disease worldwide.
      The HCV RNA genome is translated into a single polyprotein. Most of the cleavage
      sites in the non-structural (NS) polyprotein region are processed by the NS3/NS4A
      serine protease. The vital NS2-NS3 cleavage is catalyzed by the NS2 autoprotease.
      For efficient processing at the NS2/NS3 site, the NS2 cysteine protease depends
      on the NS3 serine protease domain. Despite its importance for the viral life
      cycle, the molecular details of the NS2 autoprotease activation by NS3 are poorly
      understood. Here, we report the identification of a conserved hydrophobic NS3
      surface patch that is essential for NS2 protease activation. One residue within
      this surface region is also critical for RNA replication and NS5A
      hyperphosphorylation, two processes known to depend on functional replicase
      assembly. This dual function of the NS3 surface patch prompted us to
      reinvestigate the impact of the NS2-NS3 cleavage on NS5A hyperphosphorylation.
      Interestingly, NS2-NS3 cleavage turned out to be a prerequisite for NS5A
      hyperphosphorylation, indicating that this cleavage has to occur prior to
      replicase assembly. Based on our data, we propose a sequential cascade of
      molecular events: in uncleaved NS2-NS3, the hydrophobic NS3 surface patch
      promotes NS2 protease stimulation; upon NS2-NS3 cleavage, this surface region
      becomes available for functional replicase assembly. This model explains why
      efficient NS2-3 cleavage is pivotal for HCV RNA replication. According to our
      model, the hydrophobic surface patch on NS3 represents a module critically
      involved in the temporal coordination of HCV replicase assembly. 

PMID- 25774921
TI  - Catestatin exerts direct protective effects on rat cardiomyocytes undergoing
      ischemia/reperfusion by stimulating PI3K-Akt-GSK3beta pathway and preserving
      mitochondrial membrane potential.
AB  - Catestatin (Cst) is a 21-amino acid peptide deriving from Chromogranin A. Cst
      exerts an overall protective effect against an excessive sympathetic stimulation
      of cardiovascular system, being able to antagonize catecholamine secretion and to
      reduce their positive inotropic effect, by stimulating the release of nitric
      oxide (NO) from endothelial cells. Moreover, Cst reduces ischemia/reperfusion
      (I/R) injury, improving post-ischemic cardiac function and cardiomyocyte
      survival. To define the cardioprotective signaling pathways activated by Cst (5
      nM) we used isolated adult rat cardiomyocytes undergoing simulated I/R. We
      evaluated cell viability rate with propidium iodide labeling and mitochondrial
      membrane potential (MMP) with the fluorescent probe JC-1. The involvement of Akt,
      GSK3beta, eNOS and phospholamban (PLN) cascade was studied by immunofluorescence.
      The role of PI3K-Akt/NO/cGMP pathway was also investigated by using the
      pharmacological blockers wortmannin (Wm), L-NMMA and ODQ. Our experiments
      revealed that Cst increased cell viability rate by 65% and reduced cell
      contracture in I/R cardiomyocytes. Wm, L-NMMA and ODQ limited the protective
      effect of Cst. The protective outcome of Cst was related to its ability to
      maintain MMP and to increase AktSer473, GSK3betaSer9, PLNThr17 and eNOSSer1179
      phosphorylation, while treatment with Wm abolished these effects. Thus, the
      present results show that Cst is able to exert a direct action on cardiomyocytes
      and give new insights into the molecular mechanisms involved in its protective
      effect, highlighting the PI3K/NO/cGMP pathway as the trigger and the MMP
      preservation as the end point of its action. 

PMID- 25774922
TI  - Stormwater runoff pollutant loading distributions and their correlation with
      rainfall and catchment characteristics in a rapidly industrialized city.
AB  - Fast urbanization and industrialization in developing countries result in
      significant stormwater runoff pollution, due to drastic changes in land-use, from
      rural to urban. A three-year study on the stormwater runoff pollutant loading
      distributions of industrial, parking lot and mixed commercial and residential
      catchments was conducted in the Tongsha reservoir watershed of Dongguan city, a
      typical, rapidly industrialized urban area in China. This study presents the
      changes in concentration during rainfall events, event mean concentrations (EMCs)
      and event pollution loads per unit area (EPLs). The first flush criterion, namely
      the mass first flush ratio (MFFn), was used to identify the first flush effects.
      The impacts of rainfall and catchment characterization on EMCs and pollutant
      loads percentage transported by the first 40% of runoff volume (FF40) were
      evaluated. The results indicated that the pollutant wash-off process of runoff
      during the rainfall events has significant temporal and spatial variations. The
      mean rainfall intensity (I), the impervious rate (IMR) and max 5-min intensity
      (Imax5) are the critical parameters of EMCs, while Imax5, antecedent dry days
      (ADD) and rainfall depth (RD) are the critical parameters of FF40. Intercepting
      the first 40% of runoff volume can remove 55% of TSS load, 53% of COD load, 58%
      of TN load, and 61% of TP load, respectively, according to all the storm events.
      These results may be helpful in mitigating stormwater runoff pollution for many
      other urban areas in developing countries. 

PMID- 25774923
TI  - Effects of iron overload on the bone marrow microenvironment in mice.
AB  - OBJECTIVE: Using a mouse model, Iron Overload (IO) induced bone marrow
      microenvironment injury was investigated, focusing on the involvement of reactive
      oxygen species (ROS). METHODS: Mice were intraperitoneally injected with iron
      dextran (12.5, 25, or 50 mg) every three days for two, four, and six week
      durations. Deferasirox(DFX)125 mg/ml and N-acetyl-L-cysteine (NAC) 40 mM were co
      administered. Then, bone marrow derived mesenchymal stem cells (BM-MSCs) were
      isolated and assessed for proliferation and differentiation ability, as well as
      related gene changes. Immunohistochemical analysis assessed the expression of
      haematopoietic chemokines. Supporting functions of BM-MSCs were studied by co
      culture system. RESULTS: In IO condition (25 mg/ml for 4 weeks), BM-MSCs
      exhibited proliferation deficiencies and unbalanced osteogenic/adipogenic
      differentiation. The IO BM-MSCs showed a longer double time (2.07+/-0.14 days)
      than control (1.03+/-0.07 days) (P<0.05). The immunohistochemical analysis
      demonstrated that chemokine stromal cell-derived factor-1, stem cell factor -1,
      and vascular endothelial growth factor-1 expression were decreased. The co
      cultured system demonstrated that bone marrow mononuclear cells (BMMNCs) co
      cultured with IO BM-MSCs had decreased colony forming unit (CFU) count (p<0.01),
      which indicates IO could lead to decreased hematopoietic supporting functions of
      BM-MSCs. This effect was associated with elevated phosphatidylinositol 3 kinase
      (PI3K) and reduced of Forkhead box protein O3 (FOXO3) mRNA expression, which
      could induce the generation of ROS. Results also demonstrated that NAC or DFX
      treatment could partially attenuate cell injury and inhibit signaling pathway
      striggered by IO. CONCLUSION: These results demonstrated that IO can impair the
      bone marrow microenvironment, including the quantity and quality of BM-MSCs.

PMID- 25774924
TI  - Clean graphene electrodes on organic thin-film devices via orthogonal fluorinated
      chemistry.
AB  - Graphene is a promising flexible, highly transparent, and elementally abundant
      electrode for organic electronics. Typical methods utilized to transfer large
      area films of graphene synthesized by chemical vapor deposition on metal
      catalysts are not compatible with organic thin-films, limiting the integration of
      graphene into organic optoelectronic devices. This article describes a graphene
      transfer process onto chemically sensitive organic semiconductor thin-films. The
      process incorporates an elastomeric stamp with a fluorinated polymer release
      layer that can be removed, post-transfer, via a fluorinated solvent; neither
      fluorinated material adversely affects the organic semiconductor materials. We
      used Raman spectroscopy, atomic force microscopy, and scanning electron
      microscopy to show that chemical vapor deposition graphene can be successfully
      transferred without inducing defects in the graphene film. To demonstrate our
      transfer method's compatibility with organic semiconductors, we fabricate three
      classes of organic thin-film devices: graphene field effect transistors without
      additional cleaning processes, transparent organic light-emitting diodes, and
      transparent small-molecule organic photovoltaic devices. These experiments
      demonstrate the potential of hybrid graphene/organic devices in which graphene is
      deposited directly onto underlying organic thin-film structures. 

PMID- 25774925
TI  - Does intermediate care improve patient outcomes or reduce costs?
AB  - ICUs are an essential but expensive part of all modern hospitals. With
      increasingly limited healthcare funding, methods to reduce expenditure without
      negatively influencing patient outcomes are, therefore, of interest. One possible
      solution has been the development of 'intermediate care units', which provide
      more intensive monitoring and patient management with higher nurse:patient ratios
      than the general ward but less than is offered in the ICU. However, although such
      units have been introduced in many hospitals, there is relatively little
      published, especially prospective, evidence to support the benefits of this
      approach on costs or patient outcomes. We review the available data and suggest
      that, where possible, a larger unit with combined intermediate care and intensive
      care beds in one location may be preferable in terms of greater flexibility and
      efficiency. 

PMID- 25774926
TI  - Treatment of early-onset preeclampsia with continuous positive airway pressure.
AB  - BACKGROUND: Preeclampsia is a leading cause of maternal and perinatal morbidity
      and mortality. There is no treatment for preeclampsia other than delivery. Sleep
      disordered breathing is associated with adverse pregnancy outcomes, including
      preeclampsia, but it is not known whether treatment with continuous positive
      airway pressure (CPAP) improves perinatal outcomes. CASE: We report a 35-year-old
      primigravid woman diagnosed with preeclampsia at 30 weeks of gestation. A sleep
      study confirmed severe sleep-disordered breathing, and CPAP treatment was
      started. After CPAP treatment, both clinical and biochemical markers of
      preeclampsia improved. In addition, circulating angiogenic markers of
      preeclampsia improved. As a result, the pregnancy safely continued for 30 days,
      allowing the fetus to gain gestation. CONCLUSION: Continuous positive airway
      pressure may be a novel treatment for women with early-onset preeclampsia
      associated with sleep-disordered breathing.

PMID- 25774927
TI  - Iatrogenic Wernicke encephalopathy in a patient with severe hyperemesis
      gravidarum.
AB  - BACKGROUND: Hyperemesis gravidarum complicates 0.5-2.0% of pregnancies and may
      lead to substantial nutritional deficiencies. Total parenteral nutrition can be
      used in severe cases in an attempt to avoid such deficiencies. Rarely, thiamine
      deficiency resulting in Wernicke encephalopathy occurs, with significant maternal
      morbidity. CASE: We present the case of a 30-year-old woman with hyperemesis
      gravidarum at 13 4/7 weeks of gestation treated with prolonged total parenteral
      nutrition that lacked thiamine supplementation, resulting in iatrogenic Wernicke
      encephalopathy. After high-dose intravenous thiamine repletion, she experienced
      slow resolution of her symptoms. CONCLUSION: Pregnancies complicated by
      hyperemesis gravidarum treated with total parenteral nutrition represent
      potential high-risk clinical scenarios for thiamine deficiency. Compositions of
      total parenteral nutrition are not standardized. Thus, physicians must confirm
      repletion of all essential components to avoid significant morbidity.

PMID- 25774928
TI  - Myomectomy after a vaginal delivery to treat postpartum hemorrhage resulting from
      an intracavitary leiomyoma.
AB  - BACKGROUND: Postpartum myomectomy is typically discouraged as a result of the
      risk of hemorrhage and longer operative times. However, myomectomy at the time of
      cesarean delivery or after a vaginal delivery is feasible and is sometimes
      necessary. CASE: A 38-year-old multiparous woman with a 9-cm pedunculated
      submucosal leiomyoma presented in labor and underwent a vacuum-assisted vaginal
      delivery with manual extraction of the placenta. In the immediate postpartum
      period she had bleeding and hemodynamic instability requiring blood transfusion.
      Examination under anesthesia demonstrated uterine atony and placental fragments
      adherent to the pedunculated leiomyoma. An abdominal myomectomy was performed,
      and the patient recovered normally. CONCLUSION: Although it should not be
      recommended routinely, postpartum myomectomy is feasible and can be life-saving,
      even after a vaginal delivery.

PMID- 25774929
TI  - Hymenal stenosis and fibrosis in two adult women.
AB  - BACKGROUND: Hymenal abnormalities are most commonly a result of incomplete
      apoptosis of the urogenital sinus during embryology. Infrequently, however,
      noncongenital abnormalities of the hymen can occur that can cause significant
      sequelae such as severe introital dyspareunia. CASES: We report on two adult
      women who developed severe introital dyspareunia secondary to hymenal stenosis
      and fibrosis in the absence of other vulvovaginal pathology. Neither woman had
      point tenderness of the vulvar vestibule, but their symptoms of searing pain on
      vaginal penetration was reproduced by stretching the hymen with two fingers. In
      both cases, conservative treatments with vaginal dilators in combination with
      topical hormonal therapy failed to relieve their symptoms, but both women were
      subsequently successfully treated with hymenectomy. CONCLUSION: Hymenal stenosis
      and fibrosis can develop in the absence of identifiable vulvar dermatoses. If
      conservative treatment with topical hormonal therapy and vaginal dilators is
      unsuccessful, hymenectomy can restore normal coital function.

PMID- 25774930
TI  - Cannabinoid hyperemesis syndrome: a cause of refractory nausea and vomiting in
      pregnancy.
AB  - BACKGROUND: Cannabinoid hyperemesis syndrome is a condition present among chronic
      cannabis users resulting in abdominal pain, intractable nausea and vomiting, and
      compulsive bathing behaviors. Given the recent legalization of marijuana in
      certain areas of the United States, the incidence of this condition may increase
      among pregnant women. CASE: We report the case of a pregnant 28-year-old woman
      with multiple admissions for episodic nausea and vomiting resulting in Mallory
      Weiss esophageal tears, dehydration, and abdominal pain who was noted to be
      showering compulsively during her hospitalizations. After an extensive workup for
      the etiology of her intractable nausea and pain, she was diagnosed with
      cannabinoid hyperemesis syndrome, which is treated simply with abstinence from
      marijuana use. CONCLUSION: Cannabinoid hyperemesis syndrome should be considered
      in pregnant women with intractable nausea relieved by frequent hot bathing. By
      considering this diagnosis, extensive diagnostic testing can be avoided and the
      correct therapy, abstaining from cannabis use, can be recommended.

PMID- 25774931
TI  - Pregnancy complicated by cyclic vomiting syndrome successfully treated with
      amitriptyline.
AB  - BACKGROUND: Some reports suggest that pregnancy leads to exacerbation of cyclic
      vomiting syndrome. We report a case of pregnancy complicated by cyclic vomiting
      syndrome that was successfully resolved with amitriptyline, with the subsequent
      birth of a healthy term neonate. CASE: A 27-year-old pregnant woman with cyclic
      vomiting syndrome was referred to our hospital at 12 weeks of gestation. After
      excluding other diagnoses, we administered amitriptyline, which had been
      discontinued temporarily at the time of pregnancy diagnosis. Once a therapeutic
      dose was achieved, her vomiting attacks ceased and the remainder of her prenatal
      course was uneventful. At 40 weeks of gestation, she delivered a female neonate.
      CONCLUSION: Prevention of vomiting attacks using appropriate agents is essential
      for the management of pregnancies complicated by cyclic vomiting syndrome.

PMID- 25774932
TI  - Fournier gangrene in pregnancy.
AB  - BACKGROUND: Fournier gangrene is a rare and rapidly progressive necrosis of the
      perineal and genitourinary region. Although predominantly affecting men, we
      describe an unusual presentation in pregnancy. CASE: A 30-year old primigravid
      woman in the third trimester of pregnancy presented with a history of low back
      pain. Subsequently, a diagnosis of perianal sepsis and associated Fournier
      gangrene was established. The patient underwent an emergency cesarean delivery
      followed by radical surgical debridement and colostomy. CONCLUSION: Expedited
      delivery, timely diagnosis of gangrene, urgent, extensive debridement, and broad
      spectrum antibiotic coverage contributed largely to effective management of this
      rare presentation in pregnancy.

PMID- 25774933
TI  - Catheter ablation of supraventricular tachycardia without fluoroscopy during
      pregnancy.
AB  - BACKGROUND: Although uncommon, supraventricular tachycardia is difficult to
      manage during pregnancy. Catheter ablation traditionally has been deferred owing
      to radiation exposure risks. Three-dimensional mapping is a new tool in cardiac
      electrophysiology, which is being utilized to eliminate fluoroscopy during
      catheter ablation. We report a case of ablation of supraventricular tachycardia
      during pregnancy without using fluoroscopy. CASE: A 27-year-old woman with a 22
      week twin gestation was referred for incessant supraventricular tachycardia.
      Medical management with propranolol and flecainide was unsuccessful. An
      electrophysiology study was performed with catheter navigation guided by a three
      dimensional mapping system instead of fluoroscopy. The patient underwent
      successful cryoablation. The procedure was performed without fluoroscopy or
      sedation. The patient delivered healthy twins at 35 weeks of gestation without
      complications. On follow-up at 26 months, she showed no evidence of recurrence.
      CONCLUSION: New tools in electrophysiology now make curative procedures more
      readily available to pregnant women and safer for the fetus.

PMID- 25774934
TI  - Idiopathic ovarian vein thrombosis in a nonperipartum patient.
AB  - BACKGROUND: Ovarian vein thrombosis is a rare diagnosis typically seen in the
      early peripartum period but also in other thrombophilic states such as
      postsurgery, pelvic inflammatory disease, malignancy, or sepsis. We describe a
      case of idiopathic ovarian vein thrombosis in a healthy woman far outside the
      peripartum window. CASE: The patient is a 29-year-old woman, gravida 3 para 2102,
      with no significant surgical or medical history referred for 8 months of severe
      left lower quadrant pain. An ultrasonogram revealed a nonocclusive left ovarian
      vein thrombosis. Hypercoagulable workup and all other laboratory tests were
      normal. The thrombus resolved within 2 months of starting oral anticoagulation
      therapy. CONCLUSION: This case demonstrates the importance of including
      idiopathic ovarian vein thrombosis in the differential diagnosis of nonperipartum
      females with pelvic pain.

PMID- 25774935
TI  - A Fatal Case of Strongyloidiasis in Pregnancy.
AB  - BACKGROUND: Strongyloides stercoralis is a common human parasite worldwide and
      has been associated with severe infection in immunosuppressed patients. High
      mortality rates have accompanied this severe disseminated infection. There is a
      scarcity of literature surrounding severe Strongyloides infection in pregnancy.
      CASE: A 30-year-old primigravid Haitian woman at 25 weeks of gestation presented
      with acute abdominal pain and an abnormal fetal heart tracing. Mild anemia and
      eosinophilia were laboratory abnormalities on admission. She received
      corticosteroids for the fetus and subsequently developed septic shock. Sputum and
      stool were positive for S stercoralis larvae. Hyperinfection was diagnosed,
      stillbirth occurred, and the patient died. CONCLUSION: A more global awareness
      and education surrounding helminth infection during pregnancy may improve
      response, reduce delay in diagnosis, and potentially improve outcome.

PMID- 25774936
TI  - Correlation of zinc with oxidative stress biomarkers.
AB  - Hypertension and smoking are related with oxidative stress (OS), which in turn
      reports on cellular aging. Zinc is an essential element involved in an
      individual's physiology. The aim of this study was to evaluate the relation of
      zinc levels in serum and urine with OS and cellular aging and its effect on the
      development of hypertension. In a Spanish sample with 1500 individuals, subjects
      aged 20-59 years were selected, whose zinc intake levels fell within the
      recommended limits. These individuals were classified according to their smoking
      habits and hypertensive condition. A positive correlation was found (Pearson's
      C=0.639; p=0.01) between Zn serum/urine quotient and oxidized glutathione levels
      (GSSG). Finally, risk of hypertension significantly increased when the GSSG
      levels exceeded the 75 percentile; OR=2.80 (95%CI=1.09-7.18) and AOR=3.06
      (95%CI=0.96-9.71). Low zinc levels in serum were related with OS and cellular
      aging and were, in turn, to be a risk factor for hypertension.

PMID- 25774938
TI  - Hind-casting the quantity and composition of discards by mixed demersal fisheries
      in the North Sea.
AB  - Many commercial fisheries seek to maximise the economic value of the catch that
      they bring ashore and market for human consumption by discarding undersize or low
      value fish. Information on the quantity, size and species composition of
      discarded fish is vital for stock assessments and for devising legislation to
      minimise the practice. However, except for a few major species, data are usually
      extremely sparse and reliant on observers aboard a small sample of fishing
      vessels. Expanding these data to estimate total regional discards is highly
      problematic. Here, we develop a method for utilising additional information from
      scientific trawl surveys to model the quantities of fish discarded by the
      commercial fisheries. As a case-study, we apply the model to the North Sea over
      the period 1978-2011, and show a long-term decline in the overall quantity of
      fish discarded, but an increase in the proportion of catch which is thrown away.
      The composition of discarded catch has shifted from predominantly (~80%)
      roundfish, to >50% flatfish. Undersized plaice constitute the largest single
      fraction of discards, unchanged from the beginning of the 20th century. Overall,
      around 60% of discarded fish are rejected on the basis of size rather than for
      reasons of species value or quota restrictions. The analysis shows that much more
      information can be gained on discarding by utilising additional sources of data
      rather than relying solely on information gathered by observers. In addition, it
      is clear that reducing fishing intensity and rebuilding stocks is likely to be
      more effective at reducing discards in the long term, than any technical
      legislation to outlaw the practice in the short term. 

PMID- 25774937
TI  - Non-canonical NF-kappaB signaling in rheumatoid arthritis: Dr Jekyll and Mr Hyde?
AB  - The nuclear factor-kappaB (NF-kappaB) family of transcription factors is
      essential for the expression of pro-inflammatory cytokines, but can also induce
      regulatory pathways. NF-kappaB can be activated via two distinct pathways: the
      classical or canonical pathway, and the alternative or non-canonical pathway. It
      is well established that the canonical NF-kappaB pathway is essential both in
      acute inflammatory responses and in chronic inflammatory diseases, including
      rheumatoid arthritis (RA). Although less extensively studied, the non-canonical
      NF-kappaB pathway is not only central in lymphoid organ development and adaptive
      immune responses, but is also thought to play an important role in the
      pathogenesis of RA. Importantly, this pathway appears to have cell type-specific
      functions and, since many different cell types are involved in the pathogenesis
      of RA, it is difficult to predict the net overall contribution of the non
      canonical NF-kappaB pathway to synovial inflammation. In this review, we describe
      the current understanding of non-canonical NF-kappaB signaling in various
      important cell types in the context of RA and consider the relevance to the
      pathogenesis of the disease. In addition, we discuss current drugs targeting this
      pathway, as well as future therapeutic prospects. 

PMID- 25774939
TI  - Prediction factors of recurrent ischemic events in one year after minor stroke.
AB  - BACKGROUND: The risk of a subsequent stroke following a minor stroke is high.
      However, there are no effective rating scales to predict recurrent stroke
      following a minor one. Therefore, we assessed the risk factors associated with
      recurrent ischemic stroke or transient ischemic attack (TIA) within one year of
      minor stroke onset in order to identify possible risk factors. METHODS: Eight
      hundred and sixty-three non-cardioembolic ischemic stroke patients in the Chinese
      IntraCranial AtheroSclerosis Study that presented with minor stroke, defined as
      an admission National Institutes of Health stroke scale (NIHSS) score of <=3,
      were consecutively enrolled in our study. Clinical information and imaging
      features upon admission, and any recurrent ischemic stroke or TIA within one year
      was recorded. Cox regression was used to identify risk factors associated with
      recurrent ischemic stroke or TIA within the year following stroke onset. RESULTS:
      A total of 50 patients (6.1%) experienced recurrent ischemic stroke or TIA within
      one year of minor stroke onset. Multivariate Cox regression model identified
      lower admission NIHSS score (HR, 1.75; 95% CI, 1.32 to 2.33; P<0.0001), history
      of coronary heart disease (HR, 2.62; 95% CI, 1.17 to 5.86; P = 0.02), severe
      stenosis or occlusion of large cerebral artery (HR, 4.68; 95% CI, 1.87 to 11.7; P
      = 0.001), and multiple acute cerebral infarcts (HR, 2.61; 95% CI, 1.01 to 6.80; P
      = 0.05) as independent risk factors for recurrent ischemic stroke or TIA within
      one year. CONCLUSIONS: Some minor stroke patients are at higher risk for
      recurrent ischemic stroke or TIA. Urgent and intensified therapy may be
      reasonable in these patients.

PMID- 25774940
TI  - Translation: An O-GlcNAc stamp of approval.

PMID- 25774943
TI  - A Misplaced Focus: Harmful Drinking Patterns in South Africa.

PMID- 25774942
TI  - Interleukin-21 inhibits HBV replication in vitro.
AB  - BACKGROUND: Cytokines are crucial factors in the non-cytolytic antiviral process
      to inhibit HBV gene expression and replication. Interleukin (IL)-21 has been
      suggested to play an important role in HBV infection, but it remains unknown
      whether IL-21 can inhibit HBV replication or how it inhibits HBV replication.
      METHODS: In this study, we investigated the influence of IL-21 on HBV replication
      based on human hepatoma Huh7.93 cells co-cultured with human peripheral blood
      mononuclear cells (PBMCs) and the possible correlation among IL-21, interferon
      gamma, tumour necrosis factor-alpha and IL-10. RESULTS: We demonstrated that the
      decrease of IL-21 expression and the increase of IL-10 expression in PBMCs could
      promote HBV replication in vitro. We further revealed that IL-21 is not only able
      to effectively suppress HBV replication directly but also reduce HBV replication
      by inhibition of IL-10 secretion. CONCLUSIONS: Our results provide important
      evidence for the non-cytolytic antiviral mechanism mediated by cytokines and
      their interactions in chronic hepatitis B.

PMID- 25774941
TI  - O-GlcNAc occurs cotranslationally to stabilize nascent polypeptide chains.
AB  - Nucleocytoplasmic glycosylation of proteins with O-linked N-acetylglucosamine
      residues (O-GlcNAc) is recognized as a conserved post-translational modification
      found in all metazoans. O-GlcNAc has been proposed to regulate diverse cellular
      processes. Impaired cellular O-GlcNAcylation has been found to lead to decreases
      in the levels of various proteins, which is one mechanism by which O-GlcNAc seems
      to exert its varied physiological effects. Here we show that O-GlcNAcylation also
      occurs cotranslationally. This process protects nascent polypeptide chains from
      premature degradation by decreasing cotranslational ubiquitylation. Given that
      hundreds of proteins are O-GlcNAcylated within cells, our findings suggest that
      cotranslational O-GlcNAcylation may be a phenomenon regulating proteostasis of an
      array of nucleocytoplasmic proteins. These findings set the stage to assess
      whether O-GlcNAcylation has a role in protein quality control in a manner that
      bears similarity with the role played by N-glycosylation within the secretory
      pathway. 

PMID- 25774944
TI  - Universal composition-structure-property maps for natural and biomimetic platelet
      matrix composites and stacked heterostructures.
AB  - Many natural and biomimetic platelet-matrix composites--such as nacre, silk, and
      clay-polymer-exhibit a remarkable balance of strength, toughness and/or
      stiffness, which call for a universal measure to quantify this outstanding
      feature given the structure and material characteristics of the constituents.
      Analogously, there is an urgent need to quantify the mechanics of emerging
      electronic and photonic systems such as stacked heterostructures. Here we report
      the development of a unified framework to construct universal composition
      structure-property diagrams that decode the interplay between various geometries
      and inherent material features in both platelet-matrix composites and stacked
      heterostructures. We study the effects of elastic and elastic-perfectly plastic
      matrices, overlap offset ratio and the competing mechanisms of platelet versus
      matrix failures. Validated by several 3D-printed specimens and a wide range of
      natural and synthetic materials across scales, the proposed universally valid
      diagrams have important implications for science-based engineering of numerous
      platelet-matrix composites and stacked heterostructures.

PMID- 25774945
TI  - Hypertensive Phase Following Silicone Plate Ahmed Glaucoma Valve Implantation.
AB  - PURPOSE: To estimate the incidence of hypertensive phase (HP) following silicone
      plate Ahmed glaucoma valve implantation and to explore the risk factors for
      developing HP. METHODS: A total of 325 eyes from 325 patients who underwent Ahmed
      glaucoma valve implantation for uncontrolled intraocular pressure (IOP) and were
      followed for at least 1 year were included. The HP was defined as IOP>21 mm Hg
      (with or without IOP-lowering medication) during the first 3 months after
      surgery. Eyes were divided into HP and non-HP development groups. Overall success
      was defined as reaching an IOP>5 and <22 mm Hg with (qualified success) or
      without (complete success) use of an IOP-lowering medication. Risk factors
      associated with HP development were determined by logistic regression analysis.
      RESULTS: Among 325 eyes, 101 eyes (31.1%) experienced HP. For 24 eyes (23.8%), HP
      had not resolved by postoperative year 1. The HP group showed a significantly
      higher mean preoperative IOP than the non-HP group (37.1 +/- 11.4 vs. 32.3 +/-
      11.2 mm Hg, P=0.004). The overall success rate was not significantly different
      between groups (81.2%, HP group vs. 89.7%, non-HP group; P=0.111); however, the
      complete success rate was significantly higher in the non-HP group (26.7% vs.
      43.3%, P=0.003) at postoperative year 1. HP development was positively associated
      with preoperative IOP (odds ratio, 1.025; P=0.023). CONCLUSIONS: Higher
      preoperative IOP was associated with the HP development. The non-HP group
      achieved a higher complete success rate when assessed at postoperative year 1.

PMID- 25774946
TI  - Analysis of 24-Hour IOP-related Pattern Changes After Medical Therapy.

PMID- 25774947
TI  - The complete mitochondrial genome sequence of Diptychus maculatus Steindachner
      (Cypriniformes: Cyprinidae).
AB  - Diptychus maculatus (Cypriniformes: Cyprinidae), the sole species of genus
      Diptychus, is an economically important freshwater fish widely distributed in
      Asia. In this study, we first sequenced the complete mitochondrial genome of D.
      maculatus. The genome is 16,835 bp in length, consisting of 13 protein-coding
      genes, 22 transfer RNA genes, 2 ribosomal RNA genes as well as 2 non-coding
      regions: origin of light-strand replication (OL) and control region (D-loop). The
      gene composition and order are identical with most bony fishes. The overall
      nucleotide composition of the heavy strand is 27.7% A, 26.7% T, 26.5% C and 19.1%
      G. The mitogenome data would be useful for further genetics studies, phylogenetic
      analysis, and resource protection of D. maculatus and phylogenetic analysis of
      Schizothoracine fishes.

PMID- 25774948
TI  - Development of a rapid assay to detect the jellyfish Cyanea nozakii using a loop
      mediated isothermal amplification method.
AB  - Blooms of the harmful jellyfish Cyanea nozakii, which are a severe nuisance to
      fisheries and tourisms, frequently occur in the northern East China Sea, Yellow
      Sea, and Bohai Sea. To provide early warning of this species, a simple and
      effective molecular method for identifying C. nozakii was developed using the
      loop-mediated isothermal amplification method (LAMP). The LAMP assay is highly
      specific and uses a set of four primers that target six different regions on the
      mitochondrial cytochrome c oxidase subunit I (COI) gene of C. nozakii. The
      amplification conditions, including the dNTP and betaine concentrations, the
      inner primer to outer primer concentration ratio, reaction time and temperature,
      were optimized. The LAMP assay amplified DNA extracted from tissue samples of C.
      nozakii but did not amplify DNA from other common scyphozoans and hydrozoans
      collected in the same region. In addition, the LAMP assay was more sensitive than
      conventional PCR. Therefore, the established LAMP assay is a sensitive, specific,
      fast, and easily performed method for detection of C. nozakii at different stages
      in their life cycle.

PMID- 25774949
TI  - The impact of physical connectedness on body height in Swiss conscripts.
AB  - BACKGROUND: Human populations differ in height. Recent evidence suggests that
      social networks play an important role in the regulation of adolescent growth and
      adult height. We further investigated the effect of physical connectedness on
      height. MATERIAL AND METHODS: We considered Switzerland as a geographic network
      with 169 nodes (district capitals) and 335 edges (connecting roads) and studied
      effects of connectedness on height in Swiss conscript from 1884 - 1891, 1908 -
      1910, and 2004 - 2009. We also created exponential-family random graph models to
      separate possible unspecific effects of geographic vicinity. RESULTS: In 1884 -
      1891, in 1908 - 1910, and in 2004 - 2009, 1(st), 2(nd) and 3(rd) order
      neighboring districts significantly correlate in height (p < 0.01). The
      correlations depend on the order of connectedness, they decline with increasing
      distance. Short stature districts tend to have short, tall stature districts tend
      to have tall neighbors. Random network analyses suggest direct road effects on
      height. Whereas in 1884 - 1891, direct road effects were only visible between
      1(st) order neighbors, direct road effects extended to 2(nd) and 3(rd) in 1908 -
      1910, and in 2004 - 2009, also to 4(th) order neighbors, and might reflect
      historic improvements in transportation. The spatial correlations did not
      significantly change when height was controlled for goiter (1884 - 1889) and for
      median per capita income (2006), suggesting direct road effects also in goiter
      allowed-for height and income-allowed-for height. CONCLUSION: Height in a
      district depends on height of physically connected neighboring districts. The
      association decreases with increasing distance in the net. The present data
      suggest that people can be short because their neighbors are short; or tall
      because their neighbors are tall (community effect on growth). Psycho-biological
      effects seem to control growth and development within communities that go far
      beyond our current understanding of growth regulation.

PMID- 25774950
TI  - Unilateral versus bilateral pedicle screw fixation for degenerative lumbar
      diseases: a meta-analysis of 10 randomized controlled trials.
AB  - BACKGROUND: The common and effective treatment for degenerative lumbar diseases
      is lumbar spinal fusion. Controversy still exists on the choice for
      instrumentation with spinal fusion procedures. Therefore, we conducted this meta
      analysis exclusively of RCTs to compare the clinical outcomes of patients
      receiving bilateral versus unilateral pedicle screw fixation (PSF). MATERIAL AND
      METHODS: After systematic review of published and unpublished literature, a meta
      analysis was conducted to compare the 2 treatment strategies. The methodological
      quality of the literature was assessed using the PEDro critical appraisal tool.
      RESULTS: Data synthesis showed less blood loss (P<0.001) and shorter operative
      time (P<0.001) in patients receiving unilateral PSF compared to bilateral PSF.
      However, there was no significant difference in fusion rates and functional
      outcomes between the 2 groups. CONCLUSIONS: The meta-analysis indicated no
      significant difference in fusion rates and functional outcomes between the 2
      treatment procedures, but unilateral PS fixation reduced blood loss and operative
      time.

PMID- 25774951
TI  - Colloidal nanoplatelets: Energy transfer is speeded up in 2D.

PMID- 25774952
TI  - Destruction of chemical warfare agents using metal-organic frameworks.
AB  - Chemical warfare agents containing phosphonate ester bonds are among the most
      toxic chemicals known to mankind. Recent global military events, such as the
      conflict and disarmament in Syria, have brought into focus the need to find
      effective strategies for the rapid destruction of these banned chemicals.
      Solutions are needed for immediate personal protection (for example, the
      filtration and catalytic destruction of airborne versions of agents), bulk
      destruction of chemical weapon stockpiles, protection (via coating) of clothing,
      equipment and buildings, and containment of agent spills. Solid heterogeneous
      materials such as modified activated carbon or metal oxides exhibit many
      desirable characteristics for the destruction of chemical warfare agents.
      However, low sorptive capacities, low effective active site loadings,
      deactivation of the active site, slow degradation kinetics, and/or a lack of
      tailorability offer significant room for improvement in these materials. Here, we
      report a carefully chosen metal-organic framework (MOF) material featuring high
      porosity and exceptional chemical stability that is extraordinarily effective for
      the degradation of nerve agents and their simulants. Experimental and
      computational evidence points to Lewis-acidic Zr(IV) ions as the active sites and
      to their superb accessibility as a defining element of their efficacy. 

PMID- 25774953
TI  - Design of compensated ferrimagnetic Heusler alloys for giant tunable exchange
      bias.
AB  - Rational material design can accelerate the discovery of materials with improved
      functionalities. This approach can be implemented in Heusler compounds with
      tunable magnetic sublattices to demonstrate unprecedented magnetic properties.
      Here, we have designed a family of Heusler alloys with a compensated
      ferrimagnetic state. In the vicinity of the compensation composition in Mn-Pt-Ga,
      a giant exchange bias (EB) of more than 3 T and a large coercivity are
      established. The large exchange anisotropy originates from the exchange
      interaction between the compensated host and ferrimagnetic clusters that arise
      from intrinsic anti-site disorder. Our design approach is also demonstrated on a
      second material with a magnetic transition above room temperature, Mn-Fe-Ga,
      exemplifying the universality of the concept and the feasibility of room
      temperature applications. These findings may lead to the development of magneto
      electronic devices and rare-earth-free exchange-biased hard magnets, where the
      second quadrant magnetization can be stabilized by the exchange bias. 

PMID- 25774954
TI  - Conducting polymer nanostructures for photocatalysis under visible light.
AB  - Visible-light-responsive photocatalysts can directly harvest energy from solar
      light, offering a desirable way to solve energy and environment issues. Here, we
      show that one-dimensional poly(diphenylbutadiyne) nanostructures synthesized by
      photopolymerization using a soft templating approach have high photocatalytic
      activity under visible light without the assistance of sacrificial reagents or
      precious metal co-catalysts. These polymer nanostructures are very stable even
      after repeated cycling. Transmission electron microscopy and nanoscale infrared
      characterizations reveal that the morphology and structure of the polymer
      nanostructures remain unchanged after many photocatalytic cycles. These stable
      and cheap polymer nanofibres are easy to process and can be reused without
      appreciable loss of activity. Our findings may help the development of
      semiconducting-based polymers for applications in self-cleaning surfaces,
      hydrogen generation and photovoltaics. 

PMID- 25774955
TI  - Nanolasers: Lasing from 2D atomic crystals.

PMID- 25774956
TI  - Picosecond energy transfer and multiexciton transfer outpaces Auger recombination
      in binary CdSe nanoplatelet solids.
AB  - Fluorescence resonance energy transfer (FRET) enables photosynthetic light
      harvesting, wavelength downconversion in light-emitting diodes (LEDs), and
      optical biosensing schemes. The rate and efficiency of this donor to acceptor
      transfer of excitation between chromophores dictates the utility of FRET and can
      unlock new device operation motifs including quantum-funnel solar cells, non
      contact chromophore pumping from a proximal LED, and markedly reduced gain
      thresholds. However, the fastest reported FRET time constants involving spherical
      quantum dots (0.12-1 ns; refs 7-9) do not outpace biexciton Auger recombination
      (0.01-0.1 ns; ref. 10), which impedes multiexciton-driven applications including
      electrically pumped lasers and carrier-multiplication-enhanced photovoltaics. Few
      monolayer-thick semiconductor nanoplatelets (NPLs) with tens-of-nanometre lateral
      dimensions exhibit intense optical transitions and hundreds-of-picosecond Auger
      recombination, but heretofore lack FRET characterizations. We examine binary CdSe
      NPL solids and show that interplate FRET (~6-23 ps, presumably for co-facial
      arrangements) can occur 15-50 times faster than Auger recombination and
      demonstrate multiexcitonic FRET, making such materials ideal candidates for
      advanced technologies.

PMID- 25774957
TI  - Foker Technique for the Management of Pure Esophageal Atresia: Long-Term Outcomes
      at a Single Institution.
AB  - INTRODUCTION: We present the short- and long-term outcomes in the management of
      pure long-gap esophageal atresia (LGEA) using the Foker technique (FT) of
      esophageal elongation by external axial traction at a single institution.
      METHODS: All patients undergoing esophageal atresia (EA) repair with FT over a 10
      year period were included in the study. Demographic data, birth weight,
      gestational age, associated anomalies, management, and short- and long-term
      outcomes were studied. RESULTS: Five patients (three males) were treated with FT
      in the study period, all with LGEA, with a mean birth weight of 1,926 g (range,
      541-2,890 g). Four infants had associated anomalies. Primary repair after FT
      axial traction was achieved in four patients after a mean traction time of 13
      days (range, 12-15 days). FT failed in one patient who had esophageal perforation
      from traumatic orogastric tube placement at birth and extensive matting of the
      esophagus at the time of FT attempt. The mean age at definitive esophageal
      anastomosis was 11.5 weeks (range, 8-14 weeks). In three of the five patients,
      traction sutures from the distal esophageal segment tore away, requiring a
      thoracotomy for replacement. One of the four patients had a confined leak at the
      anastomosis. All four patients developed strictures at the anastomosis, requiring
      serial dilations (mean 12 dilations, range 6-21 dilations), and three of those
      patients underwent a thoracotomy for stricture resection (two patients) or
      stricturoplasty (one patient). On long-term follow-up, all patients in whom a
      primary anastomosis was achieved had their gastrostomy closed and were on full
      oral feeds. CONCLUSION: FT was successful in achieving a primary anastomosis in
      80% of the patients with LGEA, with a significant morbidity but favorable long
      term outcomes.

PMID- 25774958
TI  - Extracorporeal Ureteric Stenting for Pediatric Laparoscopic Pyeloplasty.
AB  - INTRODUCTION: We aimed to evaluate a novel technique for ureteric stent insertion
      during dismembered pediatric laparoscopic pyeloplasty. PATIENTS AND METHODS:
      Following identification and dissection of the ureteropelvic junction (UPJ) with
      the proximal part of ureter, the ureter is dismembered just proximal to the UPJ
      at the level of the renal pelvis, allowing use of the excess pelvic tissue for
      further manipulation of the ureter. Then the abdomen is desufflated and the
      ureter delivered to the skin level. The externalized ureter is then spatulated
      and the stent inserted in an antegrade fashion to the bladder. The first stitch
      for further laparoscopic anastomosis is applied to the lower part of the
      spatulated ureteric end and then following insufflations the ureter is returned
      to the abdomen. The laparoscopic anastomosis is completed in a routine fashion.
      RESULTS: Over the past 4 years, we have used this technique in 26 children (17
      boys and 9 girls) with median age of 4 years (range, 2-18 years). Left
      pyeloplasty was performed in 16 and right pyeloplasty in the remaining 10
      patients. The mean (range) time of insertion was 6 minutes (range, 4-7 minutes).
      All stents were correctly placed. In one patient, the stent dislodged to distal
      part of the ureter. No other intraoperative or postoperative complications
      related to our technique of stent insertion were observed. CONCLUSION: Our data
      show that extracorporeal antegrade ureteric stent insertion is an easy-to-learn
      and a safe and reliable technique for pediatric dismembered pyeloplasty. It
      obviates the problem of having the stent in the pelvis during dissection and the
      need for patient repositioning.

PMID- 25774960
TI  - Responses of specialist societies to evidence for reversal of practice.

PMID- 25774961
TI  - Current state of therapeutic strategies with ranibizumab in neovascular age
      related macular degeneration.
AB  - PURPOSE OF REVIEW: To summarize the current dosing strategies in the management
      of neovascular age-related macular degeneration with intravitreal injections of
      ranibizumab. RECENT FINDINGS: A variety of therapeutic strategies has been
      recently described as an alternative to the monthly fixed treatment. The efficacy
      and local and systemic safety results of each approach is relevant in order to
      make a clinical decision and to provide patients an accurate information.
      SUMMARY: The proposed therapeutic strategies achieve positive visual outcomes
      when compared with monthly fixed regimen in the clinical trials. However, the
      real-life practice does not reflect these results. The main cause of this
      difference is the incapability to adopt any of the different strategies as the
      clinics are completely booked and this turns into a delay in the diagnostic and
      treatment visits.

PMID- 25774962
TI  - Graphene quantum dots interfaced with single bacterial spore for bio
      electromechanical devices: a graphene cytobot.
AB  - The nanoarchitecture and micromachinery of a cell can be leveraged to fabricate
      sophisticated cell-driven devices. This requires a coherent strategy to derive
      cell's mechanistic abilities, microconstruct, and chemical-texture towards such
      microtechnologies. For example, a microorganism's hydrophobic membrane
      encapsulating hygroscopic constituents allows it to sustainably withhold a high
      aquatic pressure. Further, it provides a rich surface chemistry available for
      nano-interfacing and a strong mechanical response to humidity. Here we
      demonstrate a route to incorporate a complex cellular structure into
      microelectromechanics by interfacing compatible graphene quantum dots (GQDs) with
      a highly responsive single spore microstructure. A sensitive and reproducible
      electron-tunneling width modulation of 1.63 nm within a network of GQDs
      chemically-secured on a spore was achieved via sporal hydraulics with a driving
      force of 299.75 Torrs (21.7% water at GQD junctions). The electron-transport
      activation energy and the Coulomb blockade threshold for the GQD network were 35
      meV and 31 meV, respectively; while the inter-GQD capacitance increased by 1.12
      folds at maximum hydraulic force. This is the first example of nano/bio
      interfacing with spores and will lead to the evolution of next-generation bio
      derived microarchitectures, probes for cellular/biochemical processes,
      biomicrorobotic-mechanisms, and membranes for micromechanical actuation.

PMID- 25774963
TI  - Can BRIGHT restore the glow of bivalirudin?

PMID- 25774964
TI  - Abnormal patterns of blood flow through the uterine arteries: Is it a clue for
      placental abruption in clinically suspected cases?

PMID- 25774966
TI  - Detection of Biofilm in Wounds as an Early Indicator for Risk for Tissue
      Infection and Wound Chronicity.
AB  - Wounds are dynamic environments in which dead tissue, exudate, and the bacterial
      bioburden interact in a complex manner among themselves and with the tissue of
      the host. Bacteria organize into biofilms, reducing their susceptibility to
      elimination by the host immune response and antimicrobials. Early detection of
      biofilms in wounds is crucial to successful chronic wound management; and
      although many techniques have developed to identify planktonic counterparts in
      viable wounds, few have been able to quickly and accurately identify bacterial
      biofilms. Future studies are needed to find means of identifying and monitoring
      biofilm colonization at the bedside to permit timely initiation of treatment. In
      this review, we examine some promising new technologies that hope to identify and
      quantify the process of biofilm formation in chronic wounds. 

PMID- 25774965
TI  - Fab-based bispecific antibody formats with robust biophysical properties and
      biological activity.
AB  - A myriad of innovative bispecific antibody (BsAb) platforms have been reported.
      Most require significant protein engineering to be viable from a development and
      manufacturing perspective. Single-chain variable fragments (scFvs) and diabodies
      that consist only of antibody variable domains have been used as building blocks
      for making BsAbs for decades. The drawback with Fv-only moieties is that they
      lack the native-like interactions with CH1/CL domains that make antibody Fab
      regions stable and soluble. Here, we utilize a redesigned Fab interface to
      explore 2 novel Fab-based BsAbs platforms. The redesigned Fab interface designs
      limit heavy and light chain mixing when 2 Fabs are co-expressed simultaneously,
      thus allowing the use of 2 different Fabs within a BsAb construct without the
      requirement of one or more scFvs. We describe the stability and activity of a
      HER2*HER2 IgG-Fab BsAb, and compare its biophysical and activity properties with
      those of an IgG-scFv that utilizes the variable domains of the same parental
      antibodies. We also generated an EGFR * CD3 tandem Fab protein with a similar
      format to a tandem scFv (otherwise known as a bispecific T cell engager or BiTE).
      We show that the Fab-based BsAbs have superior biophysical properties compared to
      the scFv-based BsAbs. Additionally, the Fab-based BsAbs do not simply
      recapitulate the activity of their scFv counterparts, but are shown to possess
      unique biological activity. 

PMID- 25774967
TI  - Irradiated superficial femoral artery rupture after free flap: a case report and
      review of the literature.
AB  - Radical oncologic resection can result in large soft tissue defects with exposure
      of underlying vessels. Unless immediately covered with viable soft tissue, these
      vessels are vulnerable to desiccation from air exposure and mechanical trauma.
      Local radiation treatment also contributes to a decline in vessel wall strength.
      We present an index case of a patient with prolonged exposure of her femoral bone
      and superficial femoral artery after an initial failed reconstruction of a soft
      tissue sarcoma resection defect. We provided coverage using a free latissimus
      dorsi muscle flap. Two weeks after the initial free flap operation, the patient
      was readmitted to emergency service with profuse bleeding from beneath the free
      flap. Intraoperative inspection revealed a 2-cm defect of the irradiated
      superficial femoral artery. The defect was repaired with cryopreserved human
      arterial graft, and the flap was reset. This case highlights the importance of
      immediate coverage of soft tissue defects after oncologic resection. If any
      vessels are left exposed, they should be closely inspected before a delayed flap
      coverage to rule out future sources of bleeding that may jeopardize the outcomes
      of an otherwise successful free flap operation. 

PMID- 25774968
TI  - One-Step Salvage of Infected Prosthetic Breast Reconstructions Using Antibiotic
      Impregnated Polymethylmethacrylate Plates and Concurrent Tissue Expander
      Exchange.
AB  - PURPOSE: Periprosthetic infection represents a major complication in breast
      reconstruction, frequently leading to expander-implant loss. Recent studies
      report variable success in the salvage of infected breast prostheses through
      systemic antibiotic therapy and surgical intervention. There is currently no
      consensus regarding a management algorithm for attempted salvage. The purpose of
      this pilot study was to evaluate the early outcomes of a protocol using
      antibiotic-impregnated polymethylmethacrylate (PMMA) implant placement with
      expander device exchange. METHODS: A retrospective database was queried to
      identify all patients with infected implant-based breast reconstruction who were
      treated by the study authors and who underwent attempted salvage under the study
      protocol. All patients received intravenous antibiotics followed by surgical
      debridement of the infected pocket, insertion of antibiotic-impregnated PMMA
      plates and/or beads, device exchange, and postoperative antibiotics. After
      clinical resolution of infection, tissue expansion was performed with the PMMA
      implants remaining in situ until exchanged to permanent implants. RESULTS: All
      patients with infected prosthetic breast reconstructions achieved implant pocket
      sterilization using this method. At a mean follow-up of 8.2 months (range, 1-19
      months), none of these patients have required reoperation for capsular
      contracture. One patient, while under treatment with prednisone for a rash,
      developed recurrent infection, which led to explantation of her implant. Two
      patients underwent radiation therapy while an antibiotic plate and tissue
      expander were in place, with no observed exposure or infection recurrence.
      CONCLUSIONS: Sustained local antibiotic delivery using PMMA implants and expander
      device exchange can successfully salvage an infected breast implant. Perceived
      benefits include shorter time to completed reconstruction, preserved skin
      envelope integrity, and possibly improved long-term aesthetic outcomes.

PMID- 25774969
TI  - Treatment and long-term follow-up of oral cancer postoperative sialorrhea with
      dermal sling operation.
AB  - INTRODUCTION: Reconstruction of a full-thickness defect that includes oral
      commissure presents a considerable challenge to maxillofacial and plastic
      surgeons. The goals of reconstruction are both functional and cosmetic.
      Sialorrhea, or drooling, is a major problem after flap reconstruction and
      influences the quality of life of the patient. In this article, we report on our
      experience performing a dermal sling operation to treat postoperative sialorrhea
      in patients with oral cancer. MATERIALS AND METHODS: Preoperative and
      postoperative levels of sialorrhea were evaluated based on the Drooling Severity
      and Frequency Scale. Dermal sling operations were performed on 27 patients from
      January 2000 to December 2013. In these patients, 12 cases were reviewed and
      followed up over 1 year. RESULTS: Of the 12 patients, 11 were men and one was a
      woman, with the mean age of 58 years (range, 40-79 years). There were no
      operative complications. The mean preoperative score was 4.75 (range, 3-7), and
      the mean postoperative score was 3.83 (range, 2-5). This change was significant
      (P=0.005), with valuation with the Wilcoxon signed rank test. The mean time of
      follow-up was 3.5 years (range, 1.1-7.7 years). CONCLUSIONS: The dermal sling
      operation is an acceptable treatment for postoperative sialorrhea in patients
      with commissure-involved oral cancer.

PMID- 25774970
TI  - Negative emotions impact lateral prefrontal cortex activation during theory of
      mind: An fNIRS study.
AB  - The lateral prefrontal cortex (lPFC) plays a critical role in inhibiting self
      perspective information, which is necessary for theory of mind (ToM) processing.
      Additionally, previous research has indicated that negative emotions interfere
      with lPFC activation during executive tasks. In this study, we hypothesized that
      negative emotions would inhibit lPFC activation during a ToM task. While female
      participants performed the director task following the observation of emotionally
      laden movies (neutral/negative/positive), their prefrontal hemodynamic activity
      was measured using near-infrared spectroscopy. After viewing the neutral movie,
      bilateral lPFC activity was significantly enhanced during ToM process compared to
      the control condition. In contrast, after viewing the negative movie, left lPFC
      activity during ToM process was significantly impaired. These results were
      interpreted to support the idea that negative emotions interfere with inhibition
      of self-perspective information through inactivation of the lPFC. 

PMID- 25774971
TI  - Differential profile and treatment development of drug-addicted patients
      depending on violent behaviours and/or criminal acts.
AB  - This study explored the prevalence of violent and/or criminal behaviors in drug
      addicted patients. A sample of 252 drug-addicted patients who sought treatment
      was assessed. Information was collected on violent behaviors, criminal acts,
      socio-demographic factors, consumption factors, psychopathological factors, and
      personality variables. The sample was divided into 4 groups according to the
      presence of violence and/or criminal behaviors. There were significant
      differences between the groups on some variables. In general, patients associated
      with both violence and criminal behaviors showed a greater severity in drug
      consumption and maladjustment variables, as well as a higher rate of treatment
      dropout and re-entry. 

PMID- 25774972
TI  - Tunable amphiphilicity and multifunctional applications of ionic-liquid-modified
      carbon quantum dots.
AB  - During the past decade, increasing attention has been paid to photoluminescent
      nanocarbon materials, namely, carbon quantum dots (CQDs). It is gradually
      accepted that surface engineering plays a key role in regulating the properties
      and hence the applications of the CQDs. In this paper, we prepared highly charged
      CQDs through a one-pot pyrolysis with citric acid as carbon source and a room
      temperature imidazolium-based ionic liquid as capping agent. The as-prepared CQDs
      exhibit high quantum yields up to 25.1% and are stable under various
      environments. In addition, the amphiphilicity of the CQDs can be facilely tuned
      by anion exchange, which leads to a spontaneous phase transfer between water and
      oil phase. The promising applications of the CQDs as ion sensors and fluorescent
      inks have been demonstrated. In both cases, these ionic-liquid-modified CQDs were
      found to possess novel characteristics and/or superior functions compared to
      existing ones. 

PMID- 25774973
TI  - 'The secret shame': a content analysis of online news reporting of a celebrity
      admitting smoking while pregnant.
AB  - ISSUE ADDRESSED: Around one in 10 Australian women report that they smoke while
      pregnant, and this may be a significant underestimation. In 2013, Australian
      celebrity Chrissie Swan announced publicly that she had been smoking during her
      pregnancy, generating substantial media coverage. This study sought to identify
      the main themes in the reporting of the 'Swan pregnant and admitting smoking'
      story by online news media. METHODS: Between 6 February 2013 and 18 February 2013
      inclusively, a content analysis was conducted of Australian online news items
      using the keywords: 'Chrissie Swan smoking', and 'Chrissie Swan pregnant and
      smoking'. News items were coded for nine themes. RESULTS: A total of 124 items
      were identified. The most frequent themes were: 'celebrity story' (90.32%) and
      'societal judgement of pregnant smokers' (69.35%). Less than one-half (45.97%) of
      the news items included 'quitting is hard' content and only 29.03% of the news
      items included 'smoking and health' content. Specific quit-referral content was
      found in only 13.71% of the news items. CONCLUSIONS: There was a missed
      opportunity to promote positive, non-judgemental smoking and pregnancy messages
      and health information that support pregnant women to quit smoking. SO WHAT?:
      Health promotion strategies are needed to build capacity in advocacy to promote
      positive health messages and counter societal judgement of pregnant smokers.
      Formative research into the use of celebrities and other influential women to
      promote positive empowering messages should be carried out and incorporated in
      future health promotion campaigns to improve pregnant women's ability to quit
      smoking.

PMID- 25774974
TI  - Methane clathrates in the solar system.
AB  - We review the reservoirs of methane clathrates that may exist in the different
      bodies of the Solar System. Methane was formed in the interstellar medium prior
      to having been embedded in the protosolar nebula gas phase. This molecule was
      subsequently trapped in clathrates that formed from crystalline water ice during
      the cooling of the disk and incorporated in this form into the building blocks of
      comets, icy bodies, and giant planets. Methane clathrates may play an important
      role in the evolution of planetary atmospheres. On Earth, the production of
      methane in clathrates is essentially biological, and these compounds are mostly
      found in permafrost regions or in the sediments of continental shelves. On Mars,
      methane would more likely derive from hydrothermal reactions with olivine-rich
      material. If they do exist, martian methane clathrates would be stable only at
      depth in the cryosphere and sporadically release some methane into the atmosphere
      via mechanisms that remain to be determined. In the case of Titan, most of its
      methane probably originates from the protosolar nebula, where it would have been
      trapped in the clathrates agglomerated by the satellite's building blocks.
      Methane clathrates are still believed to play an important role in the present
      state of Titan. Their presence is invoked in the satellite's subsurface as a
      means of replenishing its atmosphere with methane via outgassing episodes. The
      internal oceans of Enceladus and Europa also provide appropriate thermodynamic
      conditions that allow formation of methane clathrates. In turn, these clathrates
      might influence the composition of these liquid reservoirs. Finally, comets and
      Kuiper Belt Objects might have formed from the agglomeration of clathrates and
      pure ices in the nebula. The methane observed in comets would then result from
      the destabilization of clathrate layers in the nuclei concurrent with their
      approach to perihelion. Thermodynamic equilibrium calculations show that methane
      rich clathrate layers may exist on Pluto as well. Key Words: Methane clathrate
      Protosolar nebula-Terrestrial planets-Outer Solar System. Astrobiology 15, 308
      326. 

PMID- 25774975
TI  - Active Female Maximal and Anaerobic Threshold Cardiorespiratory Responses to Six
      Different Water Aerobics Exercises.
AB  - PURPOSE: Maximal tests conducted on land are not suitable for the prescription of
      aquatic exercises, which makes it difficult to optimize the intensity of water
      aerobics classes. The aim of the present study was to evaluate the maximal and
      anaerobic threshold cardiorespiratory responses to 6 water aerobics exercises.
      Volunteers performed 3 of the exercises in the sagittal plane and 3 in the
      frontal plane. METHOD: Twelve active female volunteers (aged 24 +/- 2 years)
      performed 6 maximal progressive test sessions. Throughout the exercise tests, we
      measured heart rate (HR) and oxygen consumption (VO2). We randomized all sessions
      with a minimum interval of 48 hr between each session. For statistical analysis,
      we used repeated-measures 1-way analysis of variance. RESULTS: Regarding the
      maximal responses, for the peak VO2, abductor hop and jumping jacks (JJ) showed
      significantly lower values than frontal kick and cross-country skiing (CCS; p <
      .001; partial eta(2) = .509), while for the peak HR, JJ showed statistically
      significantly lower responses compared with stationary running and CCS (p < .001;
      partial eta(2) = .401). At anaerobic threshold intensity expressed as the
      percentage of the maximum values, no statistically significant differences were
      found among exercises. CONCLUSION: Cardiorespiratory responses are directly
      associated with the muscle mass involved in the exercise. Thus, it is worth
      emphasizing the importance of performing a maximal test that is specific to the
      analyzed exercise so the prescription of the intensity can be safer and valid.

PMID- 25774976
TI  - Confirmed and Potential Sources of Legionella Reviewed.
AB  - Legionella bacteria are ubiquitous in natural matrices and man-made systems.
      However, it is not always clear if these reservoirs can act as source of
      infection resulting in cases of Legionnaires' disease. This review provides an
      overview of reservoirs of Legionella reported in the literature, other than
      drinking water distribution systems. Levels of evidence were developed to
      discriminate between potential and confirmed sources of Legionella. A total of 17
      systems and matrices could be classified as confirmed sources of Legionella. Many
      other man-made systems or natural matrices were not classified as a confirmed
      source, since either no patients were linked to these reservoirs or the
      supporting evidence was weak. However, these systems or matrices could play an
      important role in the transmission of infectious Legionella bacteria; they might
      not yet be considered in source investigations, resulting in an underestimation
      of their importance. To optimize source investigations it is important to have
      knowledge about all the (potential) sources of Legionella. Further research is
      needed to unravel what the contribution is of each confirmed source, and possibly
      also potential sources, to the LD disease burden. 

PMID- 25774977
TI  - Selecting revascularization strategies in patients with coronary disease.

PMID- 25774978
TI  - Comb-push ultrasound shear elastography of breast masses: initial results show
      promise.
AB  - PURPOSE OR OBJECTIVE: To evaluate the performance of Comb-push Ultrasound Shear
      Elastography (CUSE) for classification of breast masses. MATERIALS AND METHODS:
      CUSE is an ultrasound-based quantitative two-dimensional shear wave elasticity
      imaging technique, which utilizes multiple laterally distributed acoustic
      radiation force (ARF) beams to simultaneously excite the tissue and induce shear
      waves. Female patients who were categorized as having suspicious breast masses
      underwent CUSE evaluations prior to biopsy. An elasticity estimate within the
      breast mass was obtained from the CUSE shear wave speed map. Elasticity estimates
      of various types of benign and malignant masses were compared with biopsy
      results. RESULTS: Fifty-four female patients with suspicious breast masses from
      our ongoing study are presented. Our cohort included 31 malignant and 23 benign
      breast masses. Our results indicate that the mean shear wave speed was
      significantly higher in malignant masses (6 +/- 1.58 m/s) in comparison to benign
      masses (3.65 +/- 1.36 m/s). Therefore, the stiffness of the mass quantified by
      the Young's modulus is significantly higher in malignant masses. According to the
      receiver operating characteristic curve (ROC), the optimal cut-off value of 83
      kPa yields 87.10% sensitivity, 82.61% specificity, and 0.88 for the area under
      the curve (AUC). CONCLUSION: CUSE has the potential for clinical utility as a
      quantitative diagnostic imaging tool adjunct to B-mode ultrasound for
      differentiation of malignant and benign breast masses.

PMID- 25774980
TI  - Erratum.
AB  - PALLE NORDBLAD SCHMIDT, SRDAN NOVOVIC, STINE ROUG & ERIK FELDAGER (2015)
      Endoscopic, transmural drainage and necrosectomy for walled-off pancreatic and
      peripancreatic necrosis is associated with low mortality - a single-center
      experience. http://dx.doi.org/10.3109/0 0365521.2014.946078. When the above
      article was first published online, there were typographical errors and the
      legends for figure 1 and 2 were incorrect, this has now been corrected in the
      early online version. Taylor & Francis apologises for this error.

PMID- 25774981
TI  - Utility Scores In Patients With Oxygen-Dependent COPD: A Case-Control Study.
AB  - BACKGROUND: Utility measures that summarize the health-related quality of life of
      an individual using a single number usually between 0 (death) and 1 (full health)
      are useful to quantify the benefits of health care interventions in terms of
      quality-adjusted life years (QALYs) and to help prioritizing limited health
      resources from cost-effectiveness analyses among patients with different health
      conditions. OBJECTIVE: To determine utility scores in patients with oxygen
      dependent chronic obstructive pulmonary disease (COPD). METHODS: Patients with
      oxygen-dependent COPD (the cases) were matched, on a 1:2 basis, to COPD controls
      according to gender, age (+/- 5 years) and FEV1 (+/-5% predicted). Utility scores
      were obtained from the SF-6D, a measure derived from the SF-36. RESULTS: From a
      cohort of 102 patients with oxygen-dependent COPD, 68 (42 men; mean age: 71
      years; mean FEV1: 35% predicted) were successfully matched with 136 controls. We
      found clinically and statistically significant differences in mean utility scores
      between cases (0.588 +/- 0.071) and controls (0.627 +/- 0.085; p = 0.001). The
      same differences were observed in men and women. CONCLUSION: Oxygen-dependence
      adds to the burden of disease in terms of quality of life. These utility scores
      may be useful in cost-utility analyses involving patients with oxygen-dependent
      COPD.

PMID- 25774979
TI  - The neuroanatomical basis of panic disorder and social phobia in schizophrenia: a
      voxel based morphometric study.
AB  - OBJECTIVE: It is known that there is a high prevalence of certain anxiety
      disorders among schizophrenic patients, especially panic disorder and social
      phobia. However, the neural underpinnings of the comorbidity of such anxiety
      disorders and schizophrenia remain unclear. Our study aims to determine the
      neuroanatomical basis of the co-occurrence of schizophrenia with panic disorder
      and social phobia. METHODS: Voxel-based morphometry was used in order to examine
      brain structure and to measure between-group differences, comparing magnetic
      resonance images of 20 anxious patients, 20 schizophrenic patients, 20
      schizophrenic patients with comorbid anxiety, and 20 healthy control subjects.
      RESULTS: Compared to the schizophrenic patients, we observed smaller grey-matter
      volume (GMV) decreases in the dorsolateral prefrontal cortex and precentral gyrus
      in the schizophrenic-anxiety group. Additionally, the schizophrenic group showed
      significantly reduced GMV in the dorsolateral prefrontal cortex, precentral
      gyrus, orbitofrontal cortex, temporal gyrus and angular/inferior parietal gyrus
      when compared to the control group. CONCLUSIONS: Our findings suggest that the
      comorbidity of schizophrenia with panic disorder and social phobia might be
      characterized by specific neuroanatomical and clinical alterations that may be
      related to maladaptive emotion regulation related to anxiety. Even thought our
      findings need to be replicated, our study suggests that the identification of
      neural abnormalities involved in anxiety, schizophrenia and schizophrenia-anxiety
      may lead to an improved diagnosis and management of these conditions.

PMID- 25774982
TI  - Making an animal model for Korean mummy studies.
AB  - The recent findings of a series of thorough investigations into Korean mummies
      notwithstanding, many questions on the exact mechanism of the mummification
      process remain. For the purposes of a more comprehensive understanding of this
      mechanism, we employed an animal model involving Sprague-Dawley rats and
      miniature lime-soil-mixture barrier (LSMB)-surrounded Joseon tombs constructed in
      our lab. The results showed that long-duration burial in these LSMB tombs
      successfully induced animal mummification. Indeed, our gross and microscopic
      examinations confirmed that the rats were perfectly mummified in the manner of
      actual Korean mummies dating to the Joseon period. In light of the fact that the
      extent of mummification was not remarkable in other miniature tombs without LSMB,
      it seemed that the LSMB is somehow closely correlated with mummification in
      Korea. In the future, use of the present animal models and miniature tombs no
      doubt will experimentally verify the many possible factors operative in the
      specific mechanism of mummification in Korea. 

PMID- 25774984
TI  - Determinants of oligosaccharide specificity of the carbohydrate-binding modules
      of AMP-activated protein kinase.
AB  - AMP-activated protein kinase (AMPK) is an alphabetagamma heterotrimer that is
      important in regulating energy metabolism in all eukaryotes. The beta-subunit
      exists in two isoforms (beta1 and beta2) and contains a carbohydrate-binding
      module (CBM) that interacts with glycogen. The two CBM isoforms (beta1- and beta2
      CBM) are near identical in sequence and structure, yet show differences in
      carbohydrate-binding affinity. beta2-CBM binds linear carbohydrates with 4-fold
      greater affinity than beta1-CBM and binds single alpha1,6-branched carbohydrates
      up to 30-fold tighter. To understand these affinity differences, especially for
      branched carbohydrates, we determined the NMR solution structure of beta2-CBM in
      complex with the single alpha1,6-branched carbohydrate glucosyl-beta-cyclodextrin
      (gBCD) which supported the dynamic nature of the binding site, but resonance
      broadening prevented defining where the alpha1,6 branch bound. We therefore
      solved the X-ray crystal structures of beta1- and beta2-CBM, in complex with
      gBCD, to 1.7 and 2.0 A (1 A=0.1 nm) respectively. The additional threonine
      (Thr101) of beta2-CBM expands the size of the surrounding loop, creating a pocket
      that accommodates the alpha1,6 branch. Hydrogen bonds are formed between the
      alpha1,6 branch and the backbone of Trp99 and Lys102 side chain of beta2-CBM. In
      contrast, the alpha1,6 branch could not be observed in the beta1-CBM structure,
      suggesting that it does not form a specific interaction. The orientation of gBCD
      bound to beta1- and beta2-CBM is supported by thermodynamic and kinetic data
      obtained through isothermal titration calorimetry (ITC) and NMR. These results
      suggest that AMPK containing the muscle-specific beta2-isoform may have greater
      affinity for partially degraded glycogen. 

PMID- 25774983
TI  - Methyl farnesoate plays a dual role in regulating Drosophila metamorphosis.
AB  - Corpus allatum (CA) ablation results in juvenile hormone (JH) deficiency and
      pupal lethality in Drosophila. The fly CA produces and releases three
      sesquiterpenoid hormones: JH III bisepoxide (JHB3), JH III, and methyl farnesoate
      (MF). In the whole body extracts, MF is the most abundant sesquiterpenoid,
      followed by JHB3 and JH III. Knockout of JH acid methyl transferase (jhamt) did
      not result in lethality; it decreased biosynthesis of JHB3, but MF biosynthesis
      was not affected. RNAi-mediated reduction of 3-hydroxy-3-methylglutaryl CoA
      reductase (hmgcr) expression in the CA decreased biosynthesis and titers of the
      three sesquiterpenoids, resulting in partial lethality. Reducing hmgcr expression
      in the CA of the jhamt mutant further decreased MF titer to a very low level, and
      caused complete lethality. JH III, JHB3, and MF function through Met and Gce, the
      two JH receptors, and induce expression of Kr-h1, a JH primary-response gene. As
      well, a portion of MF is converted to JHB3 in the hemolymph or peripheral
      tissues. Topical application of JHB3, JH III, or MF precluded lethality in JH
      deficient animals, but not in the Met gce double mutant. Taken together, these
      experiments show that MF is produced by the larval CA and released into the
      hemolymph, from where it exerts its anti-metamorphic effects indirectly after
      conversion to JHB3, as well as acting as a hormone itself through the two JH
      receptors, Met and Gce. 

PMID- 25774985
TI  - Flavaglines Stimulate Transient Receptor Potential Melastatin Type 6 (TRPM6)
      Channel Activity.
AB  - Magnesium (Mg2+) is essential for enzymatic activity, brain function and muscle
      contraction. Blood Mg2+ concentrations are tightly regulated between 0.7 and 1.1
      mM by Mg2+ (re)absorption in kidney and intestine. The apical entry of Mg2+ in
      (re)absorbing epithelial cells is mediated by the transient receptor potential
      melastatin type 6 (TRPM6) ion channel. Here, flavaglines are described as a novel
      class of stimulatory compounds for TRPM6 activity. Flavaglines are a group of
      natural and synthetic compounds that target the ubiquitously expressed
      prohibitins and thereby affect cellular signaling. By whole-cell patch clamp
      analyses, it was demonstrated that nanomolar concentrations of flavaglines
      increases TRPM6 activity by ~2 fold. The stimulatory effects were dependent on
      the presence of the alpha-kinase domain of TRPM6, but did not require its
      phosphotransferase activity. Interestingly, it was observed that two natural
      occurring TRPM6 mutants with impaired insulin-sensitivity, TRPM6-p.Val1393Ile and
      TRPM6-p.Lys1584Glu, are not sensitive to flavagline stimulation. In conclusion,
      we have identified flavaglines as potent activators of TRPM6 activity. Our
      results suggest that flavaglines stimulate TRPM6 via the insulin receptor
      signaling pathway. 

PMID- 25774986
TI  - Executive functioning independently predicts self-rated health and improvement in
      self-rated health over time among community-dwelling older adults.
AB  - OBJECTIVES: Self-rated health, as distinct from objective measures of health, is
      a clinically informative metric among older adults. The purpose of our study was
      to examine the cognitive and psychosocial factors associated with self-rated
      health. METHODS: 624 participants over the age of 60 were assessed at baseline,
      and of these, 510 were contacted for a follow-up two years later. Measures of
      executive function and self-rated health were assessed at baseline, and self
      rated health was assessed at follow-up. We employed multiple linear regression
      analyses to investigate the relationship between executive functioning and self
      rated health, while controlling for demographic, psychosocial and biological
      variables. RESULTS: Controlling for other relevant variables, executive
      functioning independently and solely predicted self-rated health, both at a cross
      sectional level, and also over time. Loneliness was also found to cross
      sectionally predict self-rated health, although this relationship was not present
      at a longitudinal level. CONCLUSION: Older adults' self-rated health may be
      related to their executive functioning and to their loneliness. Self-rated health
      appeared to improve over time, and the extent of this improvement was also
      related to executive functioning at baseline. Self-rated health may be a
      judgement made of one's functioning, especially executive functioning, which
      changes with age and therefore may be particularly salient in the reflections of
      older adults.

PMID- 25774987
TI  - Screening, brief intervention, and referral to treatment for adolescents:
      Attitudes, perceptions, and practice of New York school-based health center
      providers.
AB  - BACKGROUND: Screening, brief intervention, and referral to treatment (SBIRT) has
      been endorsed by the American Academy of Pediatrics as an evidence-based strategy
      to address risky substance use among adolescents in primary care. However, less
      than half of pediatricians even screen adolescents for substance use. The purpose
      of this study was to identify variation in SBIRT practice and explore how program
      directors' and clinicians' attitudes and perceptions of effectiveness, role
      responsibility, and self-efficacy impact SBIRT adoption, implementation, and
      practice in school-based health centers (SBHCs). METHODS: All 162 New York State
      SBHC program directors and clinicians serving middle and high school students
      were surveyed between May and June of 2013 (40% response rate). RESULTS: Only 22%
      of participants reported practicing the SBIRT model. Of the individual SBIRT
      model components, using a standardized tool to screen students for risky
      substance use, referring students with substance use problems to specialty
      treatment, and assessing students' readiness to change were practiced least
      frequently. Less than 30% of participants felt they could be effective at helping
      students reduce substance use, 63% did not believe it was their role to use a
      standardized screening tool, and 20-30% did not feel confident performing
      specific aspects of intervention and management. Each of these factors was
      correlated with SBIRT practice frequency (P < .05). CONCLUSIONS: Findings from
      this study identify an important gap between an evidence-based SBIRT model and
      its adoption into practice within SBHCs, indicating a need for dissemination
      strategies targeting role responsibility, self-efficacy, and clinicians'
      perceptions of SBIRT effectiveness.

PMID- 25774989
TI  - Is the combination of cellulosic polymers and anionic surfactants a good strategy
      for ensuring physical stability of BCS Class II drug nanosuspensions?
AB  - Ensuring the physical stability of drug nanosuspensions prepared via wet media
      milling has been a challenge for pharmaceutical scientists. The aim of this study
      is to assess the combined use of non-ionic cellulosic polymers and anionic
      surfactants in stabilizing multiple drug nanosuspensions. Particle size of five
      drugs, i.e. azodicarbonamide (AZD), fenofibrate (FNB), griseofulvin (GF),
      ibuprofen (IBU) and phenylbutazone (PB) was reduced separately in an aqueous
      solution of hydroxypropyl cellulose (HPC) with/without sodium dodecyl sulfate
      (SDS) via a stirred media mill. Laser diffraction, scanning electron microscopy,
      thermal analysis, rheometry and electrophoresis were used to evaluate the
      breakage kinetics, storage stability, electrostatic repulsion and stabilizer
      adsorption. Without SDS, drug particles exhibited aggregation to different
      extents; FNB and GF particles aggregated the most due to low zeta potential and
      insufficient steric stabilization. Although aggregation in all milled suspensions
      was reduced due to HPC-SDS combination, FNB and IBU showed notable growth during
      7-day storage. It is concluded that the combination of non-ionic cellulosic
      polymers and anionic surfactants is generally viable for ensuring the physical
      stability of wet-milled drug nanosuspensions, provided that the surfactant
      concentration is optimized to mitigate the Ostwald ripening, whereas cellulosic
      polymers alone may provide stability for some drug suspensions. 

PMID- 25774990
TI  - "First Things First": What is the First Thing?
AB  - This op-ed piece comments on the down-side of an otherwise useful 12-step slogan,
      "First Things First," which generally refers to staying sober (not drinking or
      using no matter what). While important, there are environmental, microsocial,
      psychiatric, and neurobiological considerations that may place other needs at an
      equal or higher priority than sobriety per se. That is, other changes may be
      needed to set the stage for, or enhance efforts at sobriety, prior to or
      concurrent with attempting to quit one's drug of choice. Perhaps slogans should
      be considered in a broader context and not be taken too literally. 

PMID- 25774991
TI  - N-benzoyl-1,5-benzothiazepine and its S-oxide as vasopressin receptor ligands:
      insight into the active stereochemistry around the seven-membered ring.
AB  - The stereochemistry of N-benzoyl-1,5-benzothiazepine and its S-oxide derivatives
      as vasopressin receptor ligands was examined in detail by freezing the
      conformation with a methyl group at the C6 or C9 of 1,5-benzothiazepine. It was
      revealed that the active forms recognized by the receptors are (cis,aS) for 1,5
      benzothiazepine (5-7)-II and (cis,1S,aS) (syn) for its S-oxide (8-10)-II. The C9
      methyl derivative of 1,5-benzothiazepine S-oxide (10-II) was designed and
      synthesized, achieving the putative active syn-isomer. 

PMID- 25774994
TI  - Fluency can bias masked priming of binary judgments: evidence from an all-nonword
      task.
AB  - Using a novel all-nonword task ("Does the target have more vowels than
      consonants?"), new evidence is provided showing that processing fluency can bias
      masked priming of binary judgments. Two experiments revealed masked repetition
      priming for "yes" nonwords (e.g., NUISO) but not for "no" nonwords (e.g., RULON).
      This pattern is considered evidence that the greater ease of target processing
      induced by repetition primes was attributed to the target being a member of the
      response category associated with shorter RTs, namely the "yes" response
      category. This pattern of nonword priming effects reinforces Bodner and Masson's
      (1997) key claims: (a) a fluency-attribution process can influence masked
      priming, and (b) therefore, the masked-priming paradigm does not isolate lexical
      processes.

PMID- 25774993
TI  - Differential retrieval of past and future autobiographical experiences.
AB  - Selective retrieval can both impair and enhance memory. In this study we analysed
      the effects of retrieval practice in the recall of past and future experiences.
      The participants generated past autobiographical experiences or imagined future
      experiences using recall cues of typical autobiographical experiences obtained in
      a previous study. The experiences were presented either in chronological or
      random order. Regardless of presentation order, retrieval practice produced
      facilitation in the free recall of practised past and future experiences. No
      retrieval-induced forgetting was observed for past experiences in the ordered
      presentation, showing that the temporal organisation of autobiographical
      experiences prevents the activation of inhibitory processes. Conversely,
      inhibition was significant in the free recall of future experiences presented in
      chronological order, possibly because future experiences present less welldefined
      temporal organisation, impairing the integration that suppresses inhibitory
      processes. Thus, retrieval-induced forgetting was evident in the random
      presentation of past and future autobiographical experiences.

PMID- 25774992
TI  - Analysis of expression of programmed cell death 1 ligand 1 (PD-L1) in malignant
      pleural mesothelioma (MPM).
AB  - BACKGROUND: The increasing incidence and poor outcome associated with MPM
      requires finding effective treatment for this disease. PD1/PD-L1 pathway plays a
      central role in tumor immune evasion and appears to be predictive and prognostic
      marker. PD-L1 is expressed in many different human cancers but its role in MPM
      has yet to be established. The aim of this study is to evaluate the expression of
      PD-L1 in MPM. METHODS: 119 MPM patients (p) from two institutions between
      November 2002 and February 2014 were reviewed. Formalin-fixed, paraffin-embedded
      tissue was stained with anti-PD-L1 (clone E1L3N). Cases showing more than 1% of
      tumor cells expression of PD-L1 were considered positive. RESULTS: PD-L1 was
      analyzed in 77 p with tumor tissue available and was positive in 20.7% p (14
      samples in membrane, 16 in cytoplasm and 4 in immune infiltrate). PD-L1 intensity
      was weak in 56.2%, moderate in 25% and strong in 18.7% p. There was a significant
      relationship between PD-L1 expression and histology (PD-L1 expression 37.5% in no
      epithelioid tumor and 13.2% in epithelioid; p=0.033). The median survival in p PD
      L1 positive was 4.79 vs 16.3 months in p PD-L1 negative (p=0.012). CONCLUSIONS:
      We have shown PD-L1 is expressed in 20% of patients, associated with no
      epithelioid histology and poor prognostic in MPM. Our results suggest PD-L1
      warrants further exploration in selecting p for immunotherapy.

PMID- 25774995
TI  - Congruency effects on recognition memory: a context effect.
AB  - Two recent studies have reported that incongruent selective attention items are
      better remembered than congruent items on a surprise recognition memory test.
      These findings suggest that an increased need for cognitive control may trigger
      encoding mechanisms at the time of study that result in better recognition of
      those items at test, a form of the desirable difficulty effect. The experiments
      in this study demonstrate that this effect can depend on whether differences in
      selective attention difficulty are blocked or intermixed at the time of encoding.
      These results suggest that additional encoding time itself does not invariably
      result in better recognition for more difficult selective attention items.
      Instead, the dependence of recognition memory on encoding difficulty appears to
      reflect a context-sensitive control response to encoding difficulty.

PMID- 25774996
TI  - Individual differences in rate of encoding predict estimates of visual short-term
      memory capacity (K).
AB  - The capacity of visual short-term memory (VSTM) is commonly estimated by K scores
      obtained with a change-detection task. Contrary to common belief, K may be
      influenced not only by capacity but also by the rate at which stimuli are encoded
      into VSTM. Experiment 1 showed that, contrary to earlier conclusions, estimates
      of VSTM capacity obtained with a change-detection task are constrained by
      temporal limitations. In Experiment 2, we used change-detection and backward
      masking tasks to obtain separate within-subject estimates of K and of rate of
      encoding, respectively. A median split based on rate of encoding revealed
      significantly higher K estimates for fast encoders. Moreover, a significant
      correlation was found between K and the estimated rate of encoding. The present
      findings raise the prospect that the reported relationships between K and such
      cognitive concepts as fluid intelligence may be mediated not only by VSTM
      capacity but also by rate of encoding.

PMID- 25774997
TI  - A timely reminder about stimulus display times and other presentation parameters
      on CRTs and newer technologies.
AB  - Scientific experimentation requires specification and control of independent
      variables with accurate measurement of dependent variables. In Vision Sciences
      (here broadly including experimental psychology, cognitive neuroscience,
      psychophysics, and clinical vision), proper specification and control of stimulus
      rendering (already a thorny issue) may become more problematic as several newer
      display technologies replace cathode ray tubes (CRTs) in the lab. The present
      paper alerts researchers to spatiotemporal differences in display technologies
      and how these might affect various types of experiments. Parallels are drawn to
      similar challenges and solutions that arose during the change from cabinet-style
      tachistoscopes to computer driven CRT tachistoscopes. Technical papers outlining
      various strengths and limitations of several classes of display devices are
      introduced as a resource for the reader wanting to select appropriate displays
      for different presentation requirements. These papers emphasise the need to
      measure rather than assume display characteristics because manufacturers'
      specifications and software reports/settings may not correspond with actual
      performance. This is consistent with the call by several Vision Science and
      Psychological Science bodies to increase replications and increase detail in
      Method sections. Finally, several recent tachistoscope-based experiments, which
      focused on the same question but were implemented with different technologies,
      are compared for illustrative purposes.

PMID- 25774998
TI  - Effective equine immunization protocol for production of potent poly-specific
      antisera against Calloselasma rhodostoma, Cryptelytrops albolabris and Daboia
      siamensis.
AB  - Snake envenomation has been estimated to affect 1.8 million people annually with
      about 94,000 deaths mostly in poor tropical countries. Specific antivenoms are
      the only rational and effective therapy for these cases. Efforts are being made
      to produce effective, affordable and sufficient antivenoms for these victims. The
      immunization process, which has rarely been described in detail, is one step that
      needs to be rigorously studied and improved especially with regard to the
      production of polyspecific antisera. The polyspecific nature of therapeutic
      antivenom could obviate the need to identify the culprit snake species. The aim
      of this study was to produce potent polyspecific antisera against 3 medically
      important vipers of Thailand and its neighboring countries, namely Cryptelytrops
      albolabris "White lipped pit viper" (CA), Calleoselasma rhodostoma "Malayan pit
      viper" (CR), and Daboia siamensis "Russell's viper" (DS). Four horses were
      immunized with a mixture of the 3 viper venoms using the 'low dose, low volume
      multi-site' immunization protocol. The antisera showed rapid rise in ELISA titers
      against the 3 venoms and reached plateau at about the 8th week post-immunization.
      The in vivo neutralization potency (P) of the antisera against CA, CR and DS
      venoms was 10.40, 2.42 and 0.76 mg/ml, respectively and was much higher than the
      minimal potency limits set by Queen Soavabha Memorial Institute (QSMI). The
      corresponding potency values for the QSMI monospecific antisera against CA, CR
      and DS venoms were 7.28, 3.12 and 1.50 mg/ml, respectively. The polyspecific
      antisera also effectively neutralized the procoagulant, hemorrhagic, necrotic and
      nephrotoxic activities of the viper venoms. This effective immunization protocol
      should be useful in the production of potent polyspecific antisera against snake
      venoms, and equine antisera against tetanus, diphtheria or rabies. 

PMID- 25774999
TI  - Multicolor fluorescent labeling of cellulose nanofibrils by click chemistry.
AB  - We have chemically modified cellulose nanofibrils (CNF) with furan and maleimide
      groups, and selectively labeled the modified CNF with fluorescent probes; 7
      mercapto-4-methylcoumarin and fluorescein diacetate 5-maleimide, through two
      specific click chemistry reactions: Diels-Alder cycloaddition and the thiol
      Michael reaction. Characterization by solid-state (13)C NMR and infrared
      spectroscopy was used to follow the surface modification and estimate the
      substitution degrees. We demonstrate that the two luminescent dyes could be
      selectively labeled onto CNF, yielding a multicolor CNF that was characterized by
      UV/visible and fluorescence spectroscopies. It was demonstrated that the
      multicolor CNF could be imaged using a confocal laser scanning microscope. 

PMID- 25775000
TI  - Electron spin-lattice relaxation mechanisms of nitroxyl radicals in ionic liquids
      and conventional organic liquids: temperature dependence of a thermally activated
      process.
AB  - During the past two decades, several studies have established a significant role
      played by a thermally activated process in the electron spin relaxation of
      nitroxyl free radicals in liquid solutions. Its role has been used to explain the
      spin relaxation behavior of these radicals in a wide range of viscosities and
      microwave frequencies. However, no temperature dependence of this process has
      been reported. In this work, our main aim was to investigate the temperature
      dependence of this process in neat solvents. Electron spin-lattice relaxation
      times of 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO) and 4-hydroxy-TEMPO
      (TEMPOL), in X-band microwave frequency, were measured by the pulse saturation
      recovery technique in three room-temperature ionic liquids ([bmim][BF4],
      [emim][BF4], and [bmim][PF6]), di-isononyl phthalate, and sec-butyl benzene. The
      ionic liquids provided a wide range of viscosity in a modest range of
      temperature. An auxiliary aim was to examine whether the dynamics of a probe
      molecule dissolved in ionic liquids was different from that in conventional
      molecular liquids, as claimed in several reports on fluorescence dynamics in
      ionic liquids. This was the reason for the inclusion of di-isononyl phthalate,
      whose viscosities are similar to that of the ionic liquids in similar
      temperatures, and sec-butyl benzene. Rotational correlation times of the nitroxyl
      radicals were determined from the hyperfine dependence of the electron
      paramagnetic resonance (EPR) line widths. Observation of highly well-resolved
      proton hyperfine lines, riding over the nitrogen hyperfine lines, in the low
      viscosity regime in all the solvents, gave more accurate values of the rotational
      correlation times than the values generally measured in the absence of these
      hyperfine lines and reported in the literature. The measured rotational
      correlation times obeyed a modified Stokes-Einstein-Debye relation of temperature
      dependence in all solvents. By separating the contributions of g-anisotropy, A
      anisotropy and spin-rotation interactions from the observed electron spin-lattice
      relaxation rates, the contribution of the thermally activated process was
      obtained and compared with its expression for the temperature dependence.
      Consistent values of various fitted parameters, used in the expression of the
      thermal process, have been found, and the applicability of the expression of the
      thermally activated process to describe the temperature dependence in liquid
      solutions has been vindicated. Moderate solvent dependence of the thermally
      activated process has also been observed. The rotational correlation times and
      the spin-lattice relaxation processes of nitroxyls in ionic liquids and in
      conventional organic liquids are shown to be explicable on a similar footing,
      requiring no special treatment for ionic liquids. 

PMID- 25775001
TI  - A locked nucleic acid (LNA)-based real-time PCR assay for the rapid detection of
      multiple bacterial antibiotic resistance genes directly from positive blood
      culture.
AB  - Bacterial strains resistant to various antibiotic drugs are frequently
      encountered in clinical infections, and the rapid identification of drug
      resistant strains is highly essential for clinical treatment. We developed a
      locked nucleic acid (LNA)-based quantitative real-time PCR (LNA-qPCR) method for
      the rapid detection of 13 antibiotic resistance genes and successfully used it to
      distinguish drug-resistant bacterial strains from positive blood culture samples.
      A sequence-specific primer-probe set was designed, and the specificity of the
      assays was assessed using 27 ATCC bacterial strains and 77 negative blood culture
      samples. No cross-reaction was identified among bacterial strains and in negative
      samples, indicating 100% specificity. The sensitivity of the assays was
      determined by spiking each bacterial strain into negative blood samples, and the
      detection limit was 1-10 colony forming units (CFU) per reaction. The LNA-qPCR
      assays were first applied to 72 clinical bacterial isolates for the
      identification of known drug resistance genes, and the results were verified by
      the direct sequencing of PCR products. Finally, the LNA-qPCR assays were used for
      the detection in 47 positive blood culture samples, 19 of which (40.4%) were
      positive for antibiotic resistance genes, showing 91.5% consistency with
      phenotypic susceptibility results. In conclusion, LNA-qPCR is a reliable method
      for the rapid detection of bacterial antibiotic resistance genes and can be used
      as a supplement to phenotypic susceptibility testing for the early detection of
      antimicrobial resistance to allow the selection of appropriate antimicrobial
      treatment and to prevent the spread of resistant isolates. 

PMID- 25775002
TI  - Hedgehog signaling pathway is active in GBM with GLI1 mRNA expression showing a
      single continuous distribution rather than discrete high/low clusters.
AB  - Hedgehog (Hh) signaling pathway is a valid therapeutic target in a wide range of
      malignancies. We focus here on glioblastoma multiforme (GBM), a lethal malignancy
      of the central nervous system (CNS). By analyzing RNA-sequencing based
      transcriptomics data on 149 clinical cases of TCGA-GBM database we show here a
      strong correlation (r = 0.7) between GLI1 and PTCH1 mRNA expression--as a
      hallmark of the canonical Hh-pathway activity in this malignancy. GLI1 mRNA
      expression varied in 3 orders of magnitude among the GBM patients of the same
      cohort showing a single continuous distribution-unlike the discrete high/low-GLI1
      mRNA expressing clusters of medulloblastoma (MB). When compared with MB as a
      reference, the median GLI1 mRNA expression in GBM appeared 14.8 fold lower than
      that of the "high-Hh" cluster of MB but 5.6 fold higher than that of the "low-Hh"
      cluster of MB. Next, we demonstrated statistically significant up- and down
      regulation of GLI1 mRNA expressions in GBM patient-derived low-passage
      neurospheres in vitro by sonic hedgehog ligand-enriched conditioned media (shh
      CM) and by Hh-inhibitor drug vismodegib respectively. We also showed clinically
      achievable dose (50 MUM) of vismodegib alone to be sufficient to induce apoptosis
      and cell cycle arrest in these low-passage GBM neurospheres in vitro. Vismodegib
      showed an effect on the neurospheres, both by down-regulating GLI1 mRNA
      expression and by inducing apoptosis/cell cycle arrest, irrespective of their
      relative endogenous levels of GLI1 mRNA expression. We conclude from our study
      that this single continuous distribution pattern of GLI1 mRNA expression
      technically puts almost all GBM patients in a single group rather than discrete
      high- or low-clusters in terms of Hh-pathway activity. That is suggestive of
      therapies with Hh-pathway inhibitor drugs in this malignancy without a need for
      further stratification of patients on the basis of relative levels of Hh-pathway
      activity among them.

PMID- 25775003
TI  - Independent component analysis-based identification of covariance patterns of
      microstructural white matter damage in Alzheimer's disease.
AB  - The existing DTI studies have suggested that white matter damage constitutes an
      important part of the neurodegenerative changes in Alzheimer's disease (AD). The
      present study aimed to identify the regional covariance patterns of
      microstructural white matter changes associated with AD. In this study, we
      applied a multivariate analysis approach, independent component analysis (ICA),
      to identify covariance patterns of microstructural white matter damage based on
      fractional anisotropy (FA) skeletonised images from DTI data in 39 AD patients
      and 41 healthy controls (HCs) from the Alzheimer's Disease Neuroimaging
      Initiative database. The multivariate ICA decomposed the subject-dimension
      concatenated FA data into a mixing coefficient matrix and a source matrix. Twenty
      eight independent components (ICs) were extracted, and a two sample t-test on
      each column of the corresponding mixing coefficient matrix revealed significant
      AD/HC differences in ICA weights for 7 ICs. The covariant FA changes primarily
      involved the bilateral corona radiata, the superior longitudinal fasciculus, the
      cingulum, the hippocampal commissure, and the corpus callosum in AD patients
      compared to HCs. Our findings identified covariant white matter damage associated
      with AD based on DTI in combination with multivariate ICA, potentially expanding
      our understanding of the neuropathological mechanisms of AD. 

PMID- 25775004
TI  - On-surface synthesis of rylene-type graphene nanoribbons.
AB  - The narrowest armchair graphene nanoribbon (AGNR) with five carbons across the
      width of the GNR (5-AGNR) was synthesized on Au(111) surfaces via sequential
      dehalogenation processes in a mild condition by using 1,4,5,8
      tetrabromonaphthalene as the molecular precursor. Gold-organic hybrids were
      observed by using high-resolution scanning tunneling microscopy and considered as
      intermediate states upon AGNR formation. Scanning tunneling spectroscopy reveals
      an unexpectedly large band gap of Delta = 2.8 +/- 0.1 eV on Au(111) surface which
      can be interpreted by the hybridization of the surface states and the molecular
      states of the 5-AGNR. 

PMID- 25775005
TI  - Social media and internet driven study recruitment: evaluating a new model for
      promoting collaborator engagement and participation.
AB  - AIMS: A substantial challenge facing multicentre audit and research projects is
      timely recruitment of collaborators and their study centres. Cost-effective
      strategies are required and fee-free social media has previously been identified
      as a potential conduit. We investigated and evaluated the effectiveness of a
      novel multi-format social media and Internet strategy for targeted recruitment to
      a national multicentre cohort study. METHODS: Interventions involved a new
      Twitter account, including weekly live question-and-answer sessions, a new
      Facebook group page, online YouTube presentations and an information page on a
      national association website. Link tracking analysis was undertaken using Google
      Analytics, which was then related to subsequent registration. Social influence
      was calculated using the proprietary Klout score. RESULTS: Internet traffic
      analysis identified a total of 1562 unique registration site views, of which 285
      originated from social media (18.2%). Some 528 unique registrations were
      received, with 96 via social media platforms (18.2%). Traffic source analysis
      identified a separate national association webpage as resulting in the majority
      of registration page views (15.8%), followed by Facebook (11.9%), Twitter (4.8%)
      and YouTube (1.5%). A combination of publicity through Facebook, Twitter and the
      dedicated national association webpage contributed to the greatest rise in
      registration traffic and accounted for 312 (48%) of the total registrations
      within a 2-week period. A Twitter 'social influence' (Klout) score of 42/100 was
      obtained during this period. CONCLUSIONS: Targeted social media substantially
      aided study dissemination and collaborator recruitment. It acted as an adjunct to
      traditional methods, accounting for 18.2% of collaborator registration in a short
      time period with no associated financial costs. We provide a practical model for
      designing future recruitment campaigns, and recommend Facebook, Twitter and
      targeted websites as the most effective adjuncts for maximising cost-effective
      study recruitment.

PMID- 25775006
TI  - Constructing de novo H2O2 signaling via induced protein proximity.
AB  - A new chemical strategy has been developed to generate de novo signaling pathways
      that link a signaling molecule, H2O2, to different downstream cellular events in
      mammalian cells. This approach combines the reactivity-based H2O2 sensing with
      the chemically induced protein proximity technology. By chemically modifying
      abscisic acid with an H2O2-sensitive boronate ester probe, novel H2O2 signaling
      pathways can be engineered to induce transcription, protein translocation and
      membrane ruffle formation upon exogenous or endogenous H2O2 stimulation. This
      strategy has also been successfully applied to gibberellic acid, which provides
      the potential to build signaling networks based on orthogonal cell stimuli. 

PMID- 25775007
TI  - Ultrasensitive protein concentration detection on a micro/nanofluidic enrichment
      chip using fluorescence quenching.
AB  - A micro/nanofluidic enrichment device combined with the Forster resonance energy
      transfer (FRET) technique has been developed for sensitive detection of trace
      quantities of protein. In this approach, sample protein is first adsorbed on gold
      nanoparticles (AuNPs) to occupy part of the AuNP surface. Then, dye-labeled
      protein is added, which adsorbs to the residual active sites of the AuNP surface,
      saturating the AuNP surface with protein molecules. The unadsorbed dye-labeled
      protein remains in a free state in the system. Keeping a fixed amount of dye
      labeled protein, a high concentration of sample protein leads to more free dye
      labeled protein molecules remaining in the system, and thus a larger
      photoluminescence signal. Under the action of an electric field, the free dye
      labeled protein molecules can be efficiently enriched in front of the nanochannel
      of a micro/nanofluidic chip, which greatly amplifies the magnitude of the
      photoluminescence and improves the detection sensitivity. As a demonstration,
      bovine serum albumin (BSA) and fluorescein isothiocyanate-labeled dog serum
      albumin (FITC-DSA) are used as sample and fluorescent proteins, respectively.
      Using the proposed strategy, a detection limit of BSA as low as 2.5 pg/mL can be
      achieved, which is more than 10(3) times lower than the reported minimums in most
      sensitive commercial protein quantification methods. 

PMID- 25775008
TI  - Bioluminescent liquid light guide pad biosensor for indoor air toxicity
      monitoring.
AB  - Indoor air pollution became a recent concern found to be oftentimes worse than
      outdoor air quality. We developed a tool that is cheap and simple and enables
      continuous monitoring of air toxicity. It is a biosensor with both a
      nondisposable (monitor) and disposable (calcium alginate pads with immobilized
      bacteria) elements. Various parameters to enhance its signal have been tested
      (including the effect of the pad's orientation, it's exposure to either
      temperature or time with the air toxicant analyte, and various concentrations
      thereof). Lastly, the sensor has demonstrated its ability to sense the presence
      of chemicals in a real, indoor environment. This is the first step in the
      creation of a sensitive and simple operative tool that may be used in different
      indoor environments. 

PMID- 25775009
TI  - Correction: overexpression of wip1 is associated with biologic behavior in human
      clear cell renal cell carcinoma.

PMID- 25775010
TI  - Identification of a plasma four-microRNA panel as potential noninvasive biomarker
      for osteosarcoma.
AB  - BACKGROUND: Circulating microRNAs (miRNAs) are emerging as promising biomarkers
      for human cancer. Osteosarcoma is the most common human primary malignant bone
      tumor in children and young adults. The objective of this study was to
      investigate whether circulating miRNAs in plasma could be a useful biomarker for
      detecting osteosarcoma and monitoring tumor removal dynamics. METHODS: Plasma
      samples were obtained from 90 patients before surgery, 50 patients after one
      month of surgery, and 90 healthy individuals. The study was divided into three
      steps: First, initial screening of the profiles of circulating miRNAs in pooled
      plasma samples from healthy controls and pre-operative osteosarcoma patients
      using a TaqMan low density array (TLDA). Second, evaluation of miRNA
      concentration in individual plasma samples from 90 pre-operative osteosarcoma
      patients and 90 healthy controls by a quantitative real time PCR (qRT-PCR) assay.
      Third, evaluation of miRNA concentration in paired plasma samples from 50 pre-
      and post-operative osteosarcoma patients by qRT-PCR assay. RESULTS: Four plasma
      miRNAs including miR-195-5p, miR-199a-3p, miR-320a, and miR-374a-5p were
      significantly increased in the osteosarcoma patients. Receiver operating
      characteristics curve analysis of the combined populations demonstrated that the
      four-miRNA signature could discriminate cases from controls with an area under
      the curve of 0.9608 (95% CI 0.9307-0.9912). These 4 miRNAs were markedly
      decreased in the plasma after operation. In addition, circulating miR-195-5p and
      miR-199a-3p were correlated with metastasis status, while miR-199a-3p and miR
      320a were correlated with histological subtype. CONCLUSIONS: Our data suggest
      that altered levels of circulating miRNAs might have great potential to serve as
      novel, non-invasive biomarkers for osteosarcoma.

PMID- 25775011
TI  - The association of elastin gene variants with two angiographic subtypes of
      polypoidal choroidal vasculopathy.
AB  - OBJECTIVE: To compare the association of elastin (ELN) gene variants between two
      different angiographic phenotypes of polypoidal choroidal vasculopathy (PCV).
      METHODS: We included 411 treatment-naive PCV patients and 350 controls in the
      present study. PCV was classified into two phenotypes (152 Type 1 and 259 Type 2)
      according to the presence or absence of feeding vessels found in indocyanine
      green angiography. Single nucleotide polymorphisms (SNPs) in the ELN region
      including rs868005, rs884843, rs2301995, rs13239907 and rs2856728 were genotyped
      using TaqMan Genotyping Assays. RESULTS: In the allelic association analyses,
      rs868005 showed the strongest association with Type 2 PCV (allelic odds ratio
      1.56; p = 7.4x10(-6)), while no SNP was significantly associated with Type 1 PCV.
      Genotype association analyses revealed the significant association of rs868005
      with Type 2 PCV in log additive model and predominant model (odds ratio 1.75; p =
      1.5x10(-6) and odds ratio 1.60; p = 0.0044, respectively), but not with Type 1
      PCV. These findings were further corroborated by another control group in the
      literature. CONCLUSIONS: There may be significantly different associations in
      genetic variants of elastin between two angiographic phenotypes of PCV.

PMID- 25775012
TI  - Enhanced oral bioavailability of paclitaxel by solid dispersion granulation.
AB  - The main objective of this study was to develop novel orally administrable
      tablets containing solid dispersion granules (SDG) of amorphous paclitaxel (PTX)
      prepared by fluid bed technology, and to evaluate its in vitro dissolution and in
      vivo pharmacokinetics (PK) in beagle dogs. The SDG were prepared using optimized
      composition by fluid bed technology, and characterized for solid-state
      properties. The release study of SDG tablet (SDG-T) in simulated gastric fluid
      showed a rapid release of PTX, reaching maximum dissolution within 20 min.
      Finally, the PK profile of SDG-T and a reference formulation OraxolTM (oral
      solution formulation used in Phase I clinical study) at a dose of 60 mg orally
      with co-administration of P-gp inhibitor HM38101, and Taxol(r) at a dose of 10 mg
      intravenously (i.v.) was investigated in beagle dogs. The mean absolute BA% of
      PTX following SDG-T and OraxolTM solution was 8.23 and 6.22% in comparison to
      i.v. administration of Taxol(r). The relative BA% of PTX from SDG-T in comparison
      to OraxolTM solution was 132.25% at a dose of 60 mg following oral
      administration. In conclusion, we have successfully prepared PTX tablets with
      solid dispersion granules (SDG) of amorphous PTX using fluid bed technology that
      could provide plasma PTX concentration in the range of 10-150 ng/mL for a period
      of 24 h following oral administration in dogs with a P-gp inhibitor. Hence, this
      could be a promising formulation for PTX oral delivery and could be used in our
      intended clinical studies following pre-clinical efficacy studies. 

PMID- 25775013
TI  - In vitro and in vivo evaluation of a desonide gel-cream photostabilized with
      benzophenone-3.
AB  - CONTEXT: Our group previously reported the photoinstability of some desonide
      topical commercial formulations under direct exposure to UVA radiation.
      OBJECTIVE: This study aimed to prepare and characterize a gel-cream containing
      desonide, with greater photostability than the commercial gel-cream (C-GC).
      Benzophenone-3 (BP-3) was used as a photostabilizing agent. METHODS: The gel
      cream developed (D-GC) containing BP-3 at 0.1% was prepared and characterized
      regarding its pH, drug content, spreadability, viscosity, in vitro drug release
      and in vitro permeation. The in vivo anti-inflammatory effect was assessed by ear
      edema measurement, croton oil-induced acute skin inflammation and myeloperoxidase
      assay. RESULTS AND DISCUSSION: D-GC presented characteristics compatible with
      topical application, appropriate drug content and good spreadability, and non
      Newtonian behavior with pseudoplastic flow. D-GC showed a good photostability
      profile, presenting a desonide content of 95.70% after 48 h of exposure to UVA
      radiation, and stability under room conditions during 60 days. The amount of
      desonide released from D-GC and C-GC was 57.8 and 51.7 ug/cm2, respectively,
      measured using the vertical Franz cell. The in vitro skin permeation showed that
      desonide reached the site of action of the topical corticosteroids, from both
      formulations; however, the desonide amount retained in the dermis was lower with
      D-GC. The in vivo evaluation of topical anti-inflammatory activity indicated that
      D-GC presented the same biological effect as C-GC. CONCLUSION: D-GC represents a
      promising approach to treat dermatological disorders, since it presented
      satisfactory physicochemical characteristics, the same biological activity as C
      GC and superior photostability, conferred by the addition of BP-3 at 0.1%.

PMID- 25775014
TI  - Identification of protein tyrosine phosphatase receptor gamma extracellular
      domain (sPTPRG) as a natural soluble protein in plasma.
AB  - BACKGROUND: PTPRG is a widely expressed protein tyrosine phosphatase present in
      various isoforms. Peptides from its extracellular domain have been detected in
      plasma by proteomic techniques. We aim at characterizing the plasmatic PTPRG
      (sPTPRG) form and to identify its source. METHODOLOGY/PRINCIPAL FINDINGS: The
      expression of sPTPRG was evaluated in human plasma and murine plasma and tissues
      by immunoprecipitation and Western blotting. The polypeptides identified have an
      apparent Mr of about 120 kDa (major band) and 90 kDa (minor band) respectively.
      Full length PTPRG was identified in the 100.000*g pelleted plasma fraction,
      suggesting that it was present associated to cell-derived vesicles (exosomes).
      The release of sPTPRG by HepG2 human hepatocellular carcinoma cell line was
      induced by ethanol and sensitive to metalloproteinase and not to Furin
      inhibitors. Finally, increased levels of the plasmatic ~120 kDa isoform were
      associated with the occurrence of liver damage. CONCLUSIONS: These results
      demonstrate that sPTPRG represent a novel candidate protein biomarker in plasma
      whose increased expression is associated to hepatocyte damage. This observation
      could open a new avenue of investigation in this challenging field.

PMID- 25775015
TI  - De Novo transcriptome analysis of Oncomelania hupensis after molluscicide
      treatment by next-generation sequencing: implications for biology and future
      snail interventions.
AB  - The freshwater snail Oncomelania hupensis is the only intermediate host of
      Schistosoma japonicum, which causes schistosomiasis. This disease is endemic in
      the Far East, especially in mainland China. Because niclosamide is the only
      molluscicide recommended by the World Health Organization, 50% wettable powder of
      niclosamide ethanolamine salt (WPN), the only chemical molluscicide available in
      China, has been widely used as the main snail control method for over two
      decades. Recently, a novel molluscicide derived from niclosamide, the salt of
      quinoid-2',5-dichloro-4'-nitro-salicylanilide (Liu Dai Shui Yang An, LDS), has
      been developed and proven to have the same molluscicidal effect as WPN, with
      lower cost and significantly lower toxicity to fish than WPN. The mechanism by
      which these molluscicides cause snail death is not known. Here, we report the
      next-generation transcriptome sequencing of O. hupensis; 145,008,667 clean reads
      were generated and assembled into 254,286 unigenes. Using GO and KEGG databases,
      14,860 unigenes were assigned GO annotations and 4,686 unigenes were mapped to
      250 KEGG pathways. Many sequences involved in key processes associated with
      biological regulation and innate immunity have been identified. After the snails
      were exposed to LDS and WPN, 254 unigenes showed significant differential
      expression. These genes were shown to be involved in cell structure defects and
      the inhibition of neurohumoral transmission and energy metabolism, which may
      cause snail death. Gene expression patterns differed after exposure to LDS and
      WPN, and these differences must be elucidated by the identification and
      annotation of these unknown unigenes. We believe that this first large-scale
      transcriptome dataset for O. hupensis will provide an opportunity for the in
      depth analysis of this biomedically important freshwater snail at the molecular
      level and accelerate studies of the O. hupensis genome. The data elucidating the
      molluscicidal mechanism will be of great benefit in future snail control efforts.

PMID- 25775016
TI  - Study of water dynamics in the soaking, steaming, and solid-state fermentation of
      glutinous rice by LF-NMR: a novel monitoring approach.
AB  - Solid-state fermentation (SSF) of starchy grain is a traditional technique for
      food and alcoholic beverage production in East Asia. In the present study, low
      field nuclear magnetic resonance (LF-NMR) was introduced for the elucidation of
      water dynamics and microstructure alternations during the soaking, steaming, and
      SSF of glutinous rice as a rapid real-time monitoring method. Three different
      proton fractions with different mobilities were identified based on the degree of
      interaction between biopolymers and water. Soaking and steaming significantly
      changed the proton distribution of the sample. The different phases of SSF were
      reflected by the T2 parameters. In addition, the variations in the T2 parameters
      were explained by the microstructure changes of rice induced by SSF. The
      fermentation time and T2 parameters were sigmoidally correlated. Thus, LF-NMR may
      be an effective real-time monitoring method for SSF in starch systems.

PMID- 25775017
TI  - Nonequilibrium magnetic response of anisotropic superparamagnetic nanoparticles
      and possible artifacts in magnetic particle imaging.
AB  - Magnetic responses of superparamagnetic nanoparticles to high-frequency AC
      magnetic fields with sufficiently large amplitudes are numerically simulated to
      exactly clarify the phenomena occurring in magnetic particle imaging. When the
      magnetic anisotropy energy inevitable in actual nanoparticles is taken into
      account in considering the magnetic potential, larger nanoparticles exhibit a
      delayed response to alternations of the magnetic fields. This kind of delay is
      rather remarkable in the lower-amplitude range of the field, where the assistance
      by the Zeeman energy to thermally activated magnetization reversal is
      insufficient. In some cases, a sign inversion of the third-order harmonic
      response was found to occur at some specific amplitude, despite the lack in DC
      bias magnetic field strength. Considering the attenuation of the AC magnetic
      field generated in the human body, it is possible that the phases of the signals
      from nanoparticles deep inside the body and those near the body surface are
      completely different. This may lead to artifacts in the reconstructed image.
      Furthermore, when the magnetic/thermal torque-driven rotation of the anisotropic
      nanoparticles as well as the magnetic anisotropy energy are taken into account,
      the simulated results show that, once the easy axes are aligned toward the
      direction of the DC bias magnetic field, it takes time to randomize them at the
      field-free point. During this relaxation, the third-order harmonic response
      depends highly upon the history of the magnetic field. This is because non
      linearity of the anhysteretic magnetization curve for the superparamagnetic
      nanoparticles varies with the orientations of the easy axes. This history
      dependence may also lead to another artifact in magnetic particle imaging, when
      the scanning of the field-free point is faster than the Brownian relaxations. 

PMID- 25775018
TI  - Cyclosporin a disrupts notch signaling and vascular lumen maintenance.
AB  - Cyclosporin A (CSA) suppresses immune function by blocking the cyclophilin A and
      calcineurin/NFAT signaling pathways. In addition to immunosuppression, CSA has
      also been shown to have a wide range of effects in the cardiovascular system
      including disruption of heart valve development, smooth muscle cell
      proliferation, and angiogenesis inhibition. Circumstantial evidence has suggested
      that CSA might control Notch signaling which is also a potent regulator of
      cardiovascular function. Therefore, the goal of this project was to determine if
      CSA controls Notch and to dissect the molecular mechanism(s) by which CSA impacts
      cardiovascular homeostasis. We found that CSA blocked JAG1, but not Dll4 mediated
      Notch1 NICD cleavage in transfected 293T cells and decreased Notch signaling in
      zebrafish embryos. CSA suppression of Notch was linked to cyclophilin A but not
      calcineurin/NFAT inhibition since N-MeVal-4-CsA but not FK506 decreased Notch1
      NICD cleavage. To examine the effect of CSA on vascular development and function,
      double transgenic Fli1-GFP/Gata1-RFP zebrafish embryos were treated with CSA and
      monitored for vasculogenesis, angiogenesis, and overall cardiovascular function.
      Vascular patterning was not obviously impacted by CSA treatment and contrary to
      the anti-angiogenic activity ascribed to CSA, angiogenic sprouting of ISV vessels
      was normal in CSA treated embryos. Most strikingly, CSA treated embryos exhibited
      a progressive decline in blood flow that was associated with eventual collapse of
      vascular luminal structures. Vascular collapse in zebrafish embryos was partially
      rescued by global Notch inhibition with DAPT suggesting that disruption of normal
      Notch signaling by CSA may be linked to vascular collapse. However, multiple
      signaling pathways likely cause the vascular collapse phenotype since both
      cyclophilin A and calcineurin/NFAT were required for normal vascular function.
      Collectively, these results show that CSA is a novel inhibitor of Notch signaling
      and vascular function in zebrafish embryos. 

PMID- 25775019
TI  - Is peri-operative steroid replacement therapy necessary for the pituitary
      adenomas treated with surgery? A systematic review and meta analysis.
AB  - BACKGROUND: Patients with pituitary adenomas usually receive "stress dose"
      steroids in the peri-operative peroids. Though randomized controlled trials(RCT)
      have not been performed to assess the necessity of steroid coverage, there are
      several studies that explained the changes of adrenal function during peri
      operative peroids. The aim of the present study is to investigate whether it is
      necessary to employ conventional peri-operative glucocorticoid replacement
      therapy to all the patients undergoing surgery. METHODS: We searched studies
      addressing peri-operative steroids coverage for pituitary adenomas in the Web of
      Science, Medline and the Cochrane Library. Then we extracted studies about peri
      operative morning serum cortisol(MSC) levels, morbidity of early postoperative
      adrenal insufficiency, postoperative diabetes insipidus, relationships between
      MSC levels and adrenal integrity. We used RevMan Software to combine the results
      for meta-analysis. We used fixed-effects models for there was no significant
      heterogeneity existed. FINDINGS: There are 18 studies from 11 countries published
      between 1987 and 2013 including 1224 patients. The postoperative serum cortisol
      levels were significantly increased compared with the preoperative one in
      hypothalamic-pituitary-adrenal axis(HPAA) functions preserved
      patients(P<0.00001). The morbidity of early postoperative adrenal insufficiency
      ranged from 0.96% to 12.90%, with the overall morbidity of 5.55%(41/739). There
      was no significant differences of early postoperative diabetes insipidus between
      no supplementation patients and in supplementation patients(P=0.82). Conversely,
      there may be some disadvantages of high levels of cortisols such as high
      incidence of osteopenia and bone derangement and even the increased mortality
      rate. The patients with MSC levels of less than 60 nmol/l at 3 days after
      operation is considered as adrenal insufficient and more than 270 nmol/l as
      adrenal sufficient. To patients with MSC levels of 60-270 nmol/l, we need more
      clinical data to establish further cortisol supplementation criteria.

PMID- 25775020
TI  - Associations between green space and health in English cities: an ecological,
      cross-sectional study.
AB  - Green space has been identified as a modifiable feature of the urban environment
      and associations with physiological and psychological health have been reported
      at the local level. This study aims to assess whether these associations between
      health and green space are transferable to a larger scale, with English cities as
      the unit of analysis. We used an ecological, cross-sectional study design. We
      classified satellite-based land cover data to quantify green space coverage for
      the 50 largest cities in England. We assessed associations between city green
      space coverage with risk of death from all causes, cardiovascular disease, lung
      cancer and suicide between 2002 and 2009 using Poisson regression with random
      effect. After adjustment for age, income deprivation and air pollution, we found
      that at the city level the risk of death from all causes and a priori selected
      causes, for men and women, did not significantly differ between the greenest and
      least green cities. These findings suggest that the local health effects of urban
      green space observed at the neighbourhood level in some studies do not transfer
      to the city level. Further work is needed to establish how urban residents
      interact with local green space, in order to ascertain the most relevant measures
      of green space. 

PMID- 25775021
TI  - Transforming growth factor beta signaling is essential for the autonomous
      formation of cartilage-like tissue by expanded chondrocytes.
AB  - Cartilage is a tissue with limited self-healing potential. Hence, cartilage
      defects require surgical attention to prevent or postpone the development of
      osteoarthritis. For cell-based cartilage repair strategies, in particular
      autologous chondrocyte implantation, articular chondrocytes are isolated from
      cartilage and expanded in vitro to increase the number of cells required for
      therapy. During expansion, the cells lose the competence to autonomously form a
      cartilage-like tissue, that is in the absence of exogenously added chondrogenic
      growth factors, such as TGF-betas. We hypothesized that signaling elicited by
      autocrine and/or paracrine TGF-beta is essential for the formation of cartilage
      like tissue and that alterations within the TGF-beta signaling pathway during
      expansion interfere with this process. Primary bovine articular chondrocytes were
      harvested and expanded in monolayer culture up to passage six and the formation
      of cartilage tissue was investigated in high density pellet cultures grown for
      three weeks. Chondrocytes expanded for up to three passages maintained the
      potential for autonomous cartilage-like tissue formation. After three passages,
      however, exogenous TGF-beta1 was required to induce the formation of cartilage
      like tissue. When TGF-beta signaling was blocked by inhibiting the TGF-beta
      receptor 1 kinase, the autonomous formation of cartilage-like tissue was
      abrogated. At the initiation of pellet culture, chondrocytes from passage three
      and later showed levels of transcripts coding for TGF-beta receptors 1 and 2 and
      TGF-beta2 to be three-, five- and five-fold decreased, respectively, as compared
      to primary chondrocytes. In conclusion, the autonomous formation of cartilage
      like tissue by expanded chondrocytes is dependent on signaling induced by
      autocrine and/or paracrine TGF-beta. We propose that a decrease in the expression
      of the chondrogenic growth factor TGF-beta2 and of the TGF-beta receptors in
      expanded chondrocytes accounts for a decrease in the activity of the TGF-beta
      signaling pathway and hence for the loss of the potential for autonomous
      cartilage-like tissue formation. 

PMID- 25775022
TI  - Probing the role of interlayer coupling and coulomb interactions on electronic
      structure in few-layer MoSe2 nanostructures.
AB  - Despite the weak nature of interlayer forces in transition metal dichalcogenide
      (TMD) materials, their properties are highly dependent on the number of layers in
      the few-layer two-dimensional (2D) limit. Here, we present a combined scanning
      tunneling microscopy/spectroscopy and GW theoretical study of the electronic
      structure of high quality single- and few-layer MoSe2 grown on bilayer graphene.
      We find that the electronic (quasiparticle) bandgap, a fundamental parameter for
      transport and optical phenomena, decreases by nearly one electronvolt when going
      from one layer to three due to interlayer coupling and screening effects. Our
      results paint a clear picture of the evolution of the electronic wave function
      hybridization in the valleys of both the valence and conduction bands as the
      number of layers is changed. This demonstrates the importance of layer number and
      electron-electron interactions on van der Waals heterostructures and helps to
      clarify how their electronic properties might be tuned in future 2D nanodevices. 

PMID- 25775023
TI  - Colorectal adenomas contain multiple somatic mutations that do not coincide with
      synchronous adenocarcinoma specimens.
AB  - We have performed a comparative ultrasequencing study of multiple colorectal
      lesions obtained simultaneously from four patients. Our data show that benign
      lesions (adenomatous or hyperplastic polyps) contain a high mutational load.
      Additionally multiple synchronous colorectal lesions show non overlapping
      mutational signatures highlighting the degree of heterogeneity between multiple
      specimens in the same patient. Observations in these cases imply that considering
      not only the number of mutations but an effective oncogenic combination of
      mutations can determine the malignant progression of colorectal lesions. 

PMID- 25775024
TI  - Single arm NCRI phase II study of CHOP in combination with Ofatumumab in
      induction and maintenance for patients with newly diagnosed Richter's syndrome.
AB  - BACKGROUND: Transformation of B-cell chronic lymphocytic leukaemia (B-CLL) to
      diffuse large B cell lymphoma (DLBCL) (Richter's syndrome (RS)) is a rare (2-15%
      of patients) but catastrophic complication of B-CLL. Dose-intense chemotherapy
      regimens investigated in small single institution trials, but with the exception
      of bone marrow transplantation for a minority of patients, little has improved
      the median overall survival of patients with RS beyond eight months. Patients are
      often elderly, immunosuppressed, possess co-morbidities and have a deteriorating
      performance status. TP53 disruption is a common molecular abnormality noted in RS
      and contributes to the tumour's chemotherapy resistance. Ofatumumab is a fully
      human anti-CD20 monoclonal IgG1kappa antibody that targets a unique epitope on B
      lymphocytes. It has displayed increased binding affinity and a longer
      dissociation time when compared to rituximab resulting in improved complement
      dependent cellular cytotoxicity (CDCC); a mechanism with the potential to
      overcome apoptosis-resistance in TP53 disruption. Given the prevalence of TP53
      disruption in RS, Ofatumumab was considered a relatively non-toxic agent with a
      sound rationale to test in a prospective multicentre trial as an adjunct to CHOP
      induction and subsequent ofatumumab maintenance therapy in responding patients.
      METHODS/DESIGN: The CHOP-OR study is a prospective phase II study to evaluate the
      safety, feasibility and activity of a CHOP chemotherapy in combination with
      ofatumumab in induction and subsequent maintenance for patients with newly
      diagnosed RS. The primary objective will be the overall response rate (ORR) in
      patients with RS after six cycles of CHOP-O. The secondary objectives include
      feasibility of recruitment, progression free survival (PFS), overall survival
      (OS) and toxicity. The study will be accompanied by exploratory analysis of the
      genomic landscape of RS in newly diagnosed patients. DISCUSSION: The CHOP-OR
      trial evaluates the safety, feasibility and activity of CHOP plus Ofatumumab
      induction and Ofatumumab maintenance in new RS patients. The study is currently
      recruiting and has met the interim analysis criteria, with more than 7 of the
      first 25 participants achieving a CR or PR after six cycles of CHOP-O. The study
      has the potential to identify predictive biomarkers for this treatment modality.
      TRIAL REGISTRATION: NCT01171378.

PMID- 25775027
TI  - Correction: IFNgamma signaling endows DCs with the capacity to control type I
      inflammation during parasitic infection through promoting T-bet+ regulatory T
      cells.

PMID- 25775026
TI  - Lateral Canthus Choristoma.

PMID- 25775025
TI  - The effect of bovine parathyroid hormone withdrawal on MC3T3-E1 cell
      proliferation and phosphorus metabolism.
AB  - Hypocalcemia and hypophosphatemia are common complications after
      parathyroidectomy (PTX). Sudden removal of high circulating levels of parathyroid
      hormone (PTH) causes decreased osteoclastic resorption resulting in a decreased
      bone remodeling space. These phenomena are likely due to an increased influx of
      calcium and phosphorus into bone. However, there are currently no data to support
      this hypothesis. In this study, we found that PTX significantly reduced levels of
      PTH, calcium and phosphate. Compared with preoperative levels, after 1 year,
      postoperative PTH, calcium and phosphate levels were 295.6 +/- 173.7 pg/mL (P <
      0.05), 86.62 +/- 15.98 mg/dL (P < 0.05) and 5.56 +/- 2.03 mg/dL (P < 0.05),
      respectively. We investigated continuous bovine PTH administration as well as
      withdrawal of bovine PTH stimulation in the mouse osteoblast precursor cell line
      MC3T3-E1. MC3T3-E1 cells were cultured with continuous bovine PTH treatment for
      20 days or with transient bovine PTH treatment for 10 days. High doses of
      continuous bovine PTH exposure strongly reduced cell proliferation, alkaline
      phosphatase activity and the number of mineralized calcium nodules. However,
      withdrawal of bovine PTH (100 ng/mL) significantly increased the number of
      mineralized calcium nodules and caused a rapid decline in calcium and phosphorus
      content of culture medium. In conclusion, continuous exposure to bovine PTH
      inhibited osteoblast differentiation and reduced the formation of mineralized
      nodules. However, this inhibition was removed and mineralized nodule formation
      resumed with withdrawal of bovine PTH. According to the results of our clinical
      examinations and in vitro experiments, we hypothesize that the sudden removal of
      high levels of PTH may cause an increased influx of calcium and phosphorus into
      bone after PTX. 

PMID- 25775029
TI  - Transcriptome comparisons identify new cell markers for theca interna and
      granulosa cells from small and large antral ovarian follicles.
AB  - In studies using isolated ovarian granulosa and thecal cells it is important to
      assess the degree of cross contamination. Marker genes commonly used for
      granulosa cells include FSHR, CYP19A1 and AMH while CYP17A1 and INSL3 are used
      for thecal cells. To increase the number of marker genes available we compared
      expression microarray data from isolated theca interna with that from granulosa
      cells of bovine small (n = 10 for both theca and granulosa cells; 3-5 mm) and
      large (n = 4 for both theca and granulosa cells, > 9 mm) antral follicles.
      Validation was conducted by qRT-PCR analyses. Known markers such as CYP19A1, FSHR
      and NR5A2 and another 11 genes (LOC404103, MGARP, GLDC, CHST8, CSN2, GPX3,
      SLC35G1, CA8, CLGN, FAM78A, SLC16A3) were common to the lists of the 50 most up
      regulated genes in granulosa cells from both follicle sizes. The expression in
      theca interna was more consistent than in granulosa cells between the two
      follicle sizes. Many genes up regulated in theca interna were common to both
      sizes of follicles (MGP, DCN, ASPN, ALDH1A1, COL1A2, FN1, COL3A1, OGN, APOD,
      COL5A2, IGF2, NID1, LHFP, ACTA2, DUSP12, ACTG2, SPARCL1, FILIP1L, EGFLAM,
      ADAMDEC1, HPGD, COL12A1, FBLN5, RAMP2, COL15A1, PLK2, COL6A3, LOXL1, RARRES1,
      FLI1, LAMA2). Many of these were stromal extracellular matrix genes. MGARP, GLDC,
      CHST8, GPX3 were identified as new potential markers for granulosa cells, while
      FBLN5, OGN, RAMP2 were significantly elevated in the theca interna. 

PMID- 25775031
TI  - In Support of a National Treatment Evaluation Study.
AB  - Argument is made for the importance of conducting a national treatment evaluation
      to permit understanding of the nature and effectiveness of typical treatment
      programming. Only through such study can we hope to learn areas of success and
      failure of normative programming relative to population characteristics and
      treatment strategies, and the extent to which research-based initiatives have
      been adopted by the field. That information is central to efforts to draw up a
      research agenda appropriate to the needs of clients and the staffs responsible
      for their treatment, and to clarify and respond to gaps in the application of
      potentially useful treatment components. In spite of such need, our understanding
      of typical treatment programming and of its effectiveness is based on data
      collected from a treatment cohort of 20 years ago, although patterns of drug use,
      characteristics of clients, and the treatment components available have all
      undergone substantial change. The responsibility taken to provide such
      information to the field, once seen as a central task of research, needs to be
      reasserted to strengthen and support our treatment efforts.

PMID- 25775028
TI  - Tau depletion prevents progressive blood-brain barrier damage in a mouse model of
      tauopathy.
AB  - INTRODUCTION: The blood-brain barrier (BBB) is damaged in tauopathies, including
      progressive supranuclear palsy (PSP) and Alzheimer's disease (AD), which is
      thought to contribute to pathogenesis later in the disease course. In AD, BBB
      dysfunction has been associated with amyloid beta (Abeta) pathology, but the role
      of tau in this process is not well characterized. Since increased BBB
      permeability is found in tauopathies without Abeta pathology, like PSP, we
      suspected that tau accumulation alone could not only be sufficient, but even more
      important than Abeta for BBB damage. RESULTS: Longitudinal evaluation of brain
      tissue from the tetracycline-regulatable rTg4510 tau transgenic mouse model
      showed progressive IgG, T cell and red blood cell infiltration. The Evans blue
      (EB) dye that is excluded from the brain when the BBB is intact also permeated
      the brains of rTg4510 mice following peripheral administration, indicative of a
      bonafide BBB defect, but this was only evident later in life. Thus, despite the
      marked brain atrophy and inflammation that occurs earlier in this model, BBB
      integrity is maintained. Interestingly, BBB dysfunction emerged at the same time
      that perivascular tau emerged around major hippocampal blood vessels. However,
      when tau expression was suppressed using doxycycline, BBB integrity was
      preserved, suggesting that the BBB can be stabilized in a tauopathic brain by
      reducing tau levels. CONCLUSIONS: For the first time, these data demonstrate that
      tau alone can initiate breakdown of the BBB, but the BBB is remarkably resilient,
      maintaining its integrity in the face of marked brain atrophy, neuroinflammation
      and toxic tau accumulation. Moreover, the BBB can recover integrity when tau
      levels are reduced. Thus, late stage interventions targeting tau may slow the
      vascular contributions to cognitive impairment and dementia that occur in
      tauopathies.

PMID- 25775030
TI  - IRF8 directs stress-induced autophagy in macrophages and promotes clearance of
      Listeria monocytogenes.
AB  - Autophagy, activated by many stresses, plays a critical role in innate immune
      responses. Here we show that interferon regulatory factor 8 (IRF8) is required
      for the expression of autophagy-related genes in dendritic cells. Furthermore in
      macrophages, IRF8 is induced by multiple autophagy-inducing stresses, including
      IFNgamma and Toll-like receptor stimulation, bacterial infection, starvation and
      by macrophage colony-stimulating factor. IRF8 directly activates many genes
      involved in various steps of autophagy, promoting autophagosome formation and
      lysosomal fusion. Consequently, Irf8(-/-) macrophages are deficient in autophagic
      activity, and excessively accumulate SQSTM1 and ubiquitin-bound proteins. We show
      that clearance of Listeria monocytogenes in macrophages requires IRF8-dependent
      activation of autophagy genes and subsequent autophagic capturing and degradation
      of Listeria antigens. These processes are defective in Irf8(-/-) macrophages
      where uninhibited bacterial growth ensues. Together these data suggest that IRF8
      is a major autophagy regulator in macrophages, essential for macrophage
      maturation, survival and innate immune responses. 

PMID- 25775032
TI  - Mixed convection flow of viscoelastic fluid by a stretching cylinder with heat
      transfer.
AB  - Flow of viscoelastic fluid due to an impermeable stretching cylinder is
      discussed. Effects of mixed convection and variable thermal conductivity are
      present. Thermal conductivity is taken temperature dependent. Nonlinear partial
      differential system is reduced into the nonlinear ordinary differential system.
      Resulting nonlinear system is computed for the convergent series solutions.
      Numerical values of skin friction coefficient and Nusselt number are computed and
      discussed. The results obtained with the current method are in agreement with
      previous studies using other methods as well as theoretical ideas. Physical
      interpretation reflecting the contribution of influential parameters in the
      present flow is presented. It is hoped that present study serves as a stimulus
      for modeling further stretching flows especially in polymeric and paper
      production processes. 

PMID- 25775033
TI  - A tissue-specific scaffold for tissue engineering-based ureteral reconstruction.
AB  - Terminally differentiated somatic cells can rapidly change phenotypes when they
      are isolated from their native tissue and cultured in vitro. This problem may
      become a barrier to tissue engineering-based organ reconstruction, which utilizes
      somatic cells. The present study was designed to validate the feasibility of
      maintaining the urothelial cell phenotype in a tissue-specific ureteral scaffold.
      The tissue-specific scaffold was fabricated by blending poly (L-lactic acid)
      (PLLA) and ureteral extracellular matrix (UECM) using electrostatic spinning
      technology. PLLA was used to enhance the mechanical properties, and UECM was used
      to mimic the natural components of the ureter. Primary urothelial cells (UCs),
      derived from ureteral mucosa, were seeded onto the tissue-specific scaffold to
      assess cell adhesion, proliferation and phenotypes at designated time points. The
      results showed that UCs in the tissue-specific scaffold exhibited better
      proliferation compared to cells in pure PLLA or a PLLA-small intestinal submucosa
      (PLLA-SIS) scaffold (p<0.05). At different time points, the expression of a UC
      specific marker (UroplakinIII) in the tissue-specific scaffold was significantly
      higher than its expression in pure PLLA or a PLLA-SIS scaffold (p<0.05).
      Therefore, the tissue-specific scaffold appears to be an ideal substrate for
      promoting UC survival and phenotype maintenance. 

PMID- 25775034
TI  - Gut microbiota in multiple sclerosis: possible influence of immunomodulators.
AB  - OBJECTIVES: Differences in gut bacteria have been described in several autoimmune
      disorders. In this exploratory pilot study, we compared gut bacteria in patients
      with multiple sclerosis and healthy controls and evaluated the influence of
      glatiramer acetate and vitamin D treatment on the microbiota. METHODS: Subjects
      were otherwise healthy white women with or without relapsing-remitting multiple
      sclerosis who were vitamin D insufficient. Patients with multiple sclerosis were
      untreated or were receiving glatiramer acetate. Subjects collected stool at
      baseline and after 90 days of vitamin D3 (5000 IU/d) supplementation. The
      abundance of operational taxonomic units was evaluated by hybridization of 16S
      rRNA to a DNA microarray. RESULTS: While there was overlap of gut bacterial
      communities, the abundance of some operational taxonomic units, including
      Faecalibacterium, was lower in patients with multiple sclerosis. Glatiramer
      acetate-treated patients with multiple sclerosis showed differences in community
      composition compared with untreated subjects, including Bacteroidaceae,
      Faecalibacterium, Ruminococcus, Lactobacillaceae, Clostridium, and other
      Clostridiales. Compared with the other groups, untreated patients with multiple
      sclerosis had an increase in the Akkermansia, Faecalibacterium, and Coprococcus
      genera after vitamin D supplementation. CONCLUSIONS: While overall bacterial
      communities were similar, specific operational taxonomic units differed between
      healthy controls and patients with multiple sclerosis. Glatiramer acetate and
      vitamin D supplementation were associated with differences or changes in the
      microbiota. This study was exploratory, and larger studies are needed to confirm
      these preliminary results.

PMID- 25775035
TI  - HEB associates with PRC2 and SMAD2/3 to regulate developmental fates.
AB  - In embryonic stem cells, extracellular signals are required to derepress
      developmental promoters to drive lineage specification, but the proteins involved
      in connecting extrinsic cues to relaxation of chromatin remain unknown. We
      demonstrate that the helix-loop-helix (HLH) protein, HEB, directly associates
      with the Polycomb repressive complex 2 (PRC2) at a subset of developmental
      promoters, including at genes involved in mesoderm and endoderm specification and
      at the Hox and Fox gene families. While we show that depletion of HEB does not
      affect mouse ESCs, it does cause premature differentiation after exposure to
      Activin. Further, we find that HEB deposition at developmental promoters is
      dependent upon PRC2 and independent of Nodal, whereas HEB association with
      SMAD2/3 elements is dependent of Nodal, but independent of PRC2. We suggest that
      HEB is a fundamental link between Nodal signalling, the derepression of a
      specific class of poised promoters during differentiation, and lineage
      specification in mouse ESCs. 

PMID- 25775036
TI  - Improved viability of Lactobacillus acidophilus NRRL-B 4495 during freeze-drying
      in whey protein-pullulan microcapsules.
AB  - In this research, pullulan was incorporated in protein-based encapsulation matrix
      in order to assess its cryoprotective effect on the viability of freeze-dried
      (FD) probiotic Lactobacillus acidophilus NRRL-B 4495. This study demonstrated
      that pullulan in encapsulation matrix resulted in a 90.4% survival rate as
      compared to 88.1% for whey protein (WPI) encapsulated cells. The protective
      effects of pullulan on the survival of FD-encapsulated cells in gastrointestinal
      conditions were compared. FD WPI-pullulan capsules retained higher survived cell
      numbers (7.10 log CFU/g) than those of FD WPI capsules (6.03 log CFU/g) after
      simulated gastric juice exposure. Additionally, use of pullulan resulted in an
      increased viability after bile exposure. FD-free bacteria exhibited 2.18 log
      CFU/g reduction, while FD WPI and FD WPI-pullulan encapsulated bacteria showed
      0.95 and 0.49 log CFU/g reduction after 24 h exposure to bile solution,
      respectively. Morphology of the FD microcapsules was visualized by scanning
      electron microscopy. 

PMID- 25775037
TI  - Microencapsulation of insulin using a W/O/W double emulsion followed by complex
      coacervation to provide protection in the gastrointestinal tract.
AB  - Microcapsules containing insulin were prepared using a combination of a W/O/W
      double emulsion and complex coacervation between WPI (used as a hydrophilic
      emulsifier) and CMC or SA with further spray drying of the microcapsules in order
      to provide protection in the gastrointestinal tract. The microcapsules prepared
      exhibited high encapsulation efficiency and showed the typical structure of a
      double emulsion. After spray drying of these microcapsules, the integrity of the
      W/O/W double emulsion was maintained and the biological residual activity
      remained high when using the combination of 180  degrees C inlet air temperature
      and 70  degrees C outlet air temperature. The microcapsules exhibited low
      solubility at pH 2 and high solubility at pH 7 so they might protect insulin at
      acid pH values in the stomach and release it at intestinal pH values. The
      microcapsules developed in this study seem to be a promising oral delivery
      vehicle for insulin or other therapeutic proteins. 

PMID- 25775038
TI  - Survival of free and microencapsulated Bifidobacterium: effect of honey addition.
AB  - This study evaluated the effect of honey addition on the viability of free and
      emulsion encapsulated cells of two strains of Bifidobacterium that underwent
      simulation of human upper gastrointestinal transit. In the control condition,
      without honey, free cells were drastically reduced after exposure to
      gastrointestinal conditions. The reduction was more pronounced with
      Bifidobacterium J7 of human origin. On the other hand, when cells were
      encapsulated, the viability reduction was higher for strain Bifidobacterium Bb12.
      The microencapsulation improved the viability maintenance of both Bifidobacterium
      strains, in recommended amounts for probiotic activity, after exposure to
      simulated gastrointestinal conditions. Moreover, suspending free cells of both
      Bifidobacterium strains in honey solutions resulted in a protective effect,
      equivalent to the plain microencapsulation with sodium alginate 3%. It is
      concluded that microencapsulation and the addition of honey improved the ability
      of Bifidobacterium to tolerate gastrointestinal conditions in vitro. 

PMID- 25775039
TI  - Acellular implantable and injectable hydrogels for vascular regeneration.
AB  - In recent years, therapeutic angiogenesis has been sought as a treatment for many
      vascular disorders, including peripheral artery disease and coronary artery
      disease. As mechanisms of angiogenesis and vasculogenesis have been elucidated,
      the functions of important growth factors and cytokines have been identified.
      Bolus injections of these growth factors have had limited clinical success
      because of their short half-lives and difficulty controlling their systemic
      effects. Over the last 15 years, many hydrogel technologies have been developed
      to help solve these issues. Many of these hydrogel technologies have aimed to
      conjugate pro-angiogenic growth factors with controlled, local delivery. However,
      in order to attain maximum therapeutic effects, multiple growth factors are
      necessary, owing to the complex nature of the angiogenic pathway. While many
      groups have successfully conjugated growth factors controlling different steps of
      angiogenesis, clinical success remains elusive and will likely rely on both
      spatial and temporal control over growth factor release as these systems evolve
      in the future. A number of physical factors of the microenvironment also play a
      vital role in regulating angiogenesis, including ultrastructure, degradability,
      and matrix stiffness. Vascular engineering research has been advanced by design
      of hydrogels that decouple the effects of physical and biological factors, to
      enhance the understanding of the myriad factors involved in vascular
      morphogenesis. Recently, hydrogels have been developed to influence
      microenvironmental factors, such as hypoxia, upstream of growth factor
      production. By triggering angiogenesis further upstream, a more robust angiogenic
      response may be achieved by promoting the entire array of growth factors and
      cytokines necessary for new vessel formation and stabilization. As the field
      moves forward, study of other upstream environmental factors will likely provide
      insights into the formation of neovascularature as well as providing
      opportunities for design of novel hydrogel systems with vast therapeutic
      potential.

PMID- 25775040
TI  - A call for new thoughts about what might influence human brain aging: aging,
      apolipoprotein E, and amyloid.

PMID- 25775041
TI  - Are movements necessary for the sense of body ownership? Evidence from the rubber
      hand illusion in pure hemiplegic patients.
AB  - A question still debated within cognitive neuroscience is whether signals present
      during actions significantly contribute to the emergence of human's body
      ownership. In the present study, we aimed at answer this question by means of a
      neuropsychological approach. We administered the classical rubber hand illusion
      paradigm to a group of healthy participants and to a group of neurological
      patients affected by a complete left upper limb hemiplegia, but without any
      propriceptive/tactile deficits. The illusion strength was measured both
      subjectively (i.e., by a self-report questionnaire) and behaviorally (i.e., the
      location of one's own hand is shifted towards the rubber hand). We aimed at
      examining whether, and to which extent, an enduring absence of movements related
      signals affects body ownership. Our results showed that patients displayed,
      respect to healthy participants, stronger illusory effects when the left
      (affected) hand was stimulated and no effects when the right (unaffected) hand
      was stimulated. In other words, hemiplegics had a weaker/more flexible sense of
      body ownership for the affected hand, but an enhanced/more rigid one for the
      healthy hand. Possible interpretations of such asymmetrical distribution of body
      ownership, as well as limits of our results, are discussed. Broadly speaking, our
      findings suggest that the alteration of the normal flow of signals present during
      movements impacts on human's body ownership. This in turn, means that movements
      have a role per se in developing and maintaining a coherent body ownership. 

PMID- 25775042
TI  - Direct visualization of newly synthesized target proteins in situ.
AB  - Protein synthesis is a dynamic process that tunes the cellular proteome in
      response to internal and external demands. Metabolic labeling approaches identify
      the general proteomic response but cannot visualize specific newly synthesized
      proteins within cells. Here we describe a technique that couples noncanonical
      amino acid tagging or puromycylation with the proximity ligation assay to
      visualize specific newly synthesized proteins and monitor their origin,
      redistribution and turnover in situ. 

PMID- 25775043
TI  - Functional annotation of native enhancers with a Cas9-histone demethylase fusion.
AB  - Understanding of mammalian enhancers is limited by the lack of a technology to
      rapidly and thoroughly test the cell type-specific function. Here, we use a
      nuclease-deficient Cas9 (dCas9)-histone demethylase fusion to functionally
      characterize previously described and new enhancer elements for their roles in
      the embryonic stem cell state. Further, we distinguish the mechanism of action of
      dCas9-LSD1 at enhancers from previous dCas9-effectors. 

PMID- 25775044
TI  - CIDRE: an illumination-correction method for optical microscopy.
AB  - Uneven illumination affects every image acquired by a microscope. It is often
      overlooked, but it can introduce considerable bias to image measurements. The
      most reliable correction methods require special reference images, and
      retrospective alternatives do not fully model the correction process. Our
      approach overcomes these issues for most optical microscopy applications without
      the need for reference images. 

PMID- 25775045
TI  - Catchup: a mouse model for imaging-based tracking and modulation of neutrophil
      granulocytes.
AB  - Neutrophil granulocyte biology is a central issue of immunological research, but
      the lack of animal models that allow for neutrophil-selective genetic
      manipulation has delayed progress. By modulating the neutrophil-specific locus
      Ly6G with a knock-in allele expressing Cre recombinase and the fluorescent
      protein tdTomato, we generated a mouse model termed Catchup that exhibits strong
      neutrophil specificity. Transgene activity was found only in very few eosinophils
      and basophils and was undetectable in bone marrow precursors, including
      granulomonocytic progenitors (GMPs). Cre-mediated reporter-gene activation
      allowed for intravital two-photon microscopy of neutrophils without adoptive
      transfer. Homozygous animals were Ly6G deficient but showed normal leukocyte
      cellularity in all measured organs. Ly6G-deficient neutrophils were functionally
      normal in vitro and in multiple models of sterile or infectious inflammation in
      vivo. However, Cre-mediated deletion of FcgammaRIV in neutrophils reduced the
      cells' recruitment to immune-complex-mediated peritonitis, suggesting a cell
      intrinsic role for activating Fc receptors in neutrophil trafficking. 

PMID- 25775046
TI  - Determination of variation parameters as a crucial step in designing TMT-based
      clinical proteomics experiments.
AB  - In quantitative shotgun proteomic analyses by liquid chromatography and mass
      spectrometry, a rigid study design is necessary in order to obtain statistically
      relevant results. Hypothesis testing, sample size calculation and power
      estimation are fundamental concepts that require consideration upon designing an
      experiment. For this reason, the reproducibility and variability of the proteomic
      platform needs to be assessed. In this study, we evaluate the technical (sample
      preparation), labeling (isobaric labels), and total (biological + technical +
      labeling + experimental) variability and reproducibility of a workflow that
      employs a shotgun LC-MS/MS approach in combination with TMT peptide labeling for
      the quantification of peripheral blood mononuclear cell (PBMC) proteome. We
      illustrate that the variability induced by TMT labeling is small when compared to
      the technical variation. The latter is also responsible for a substantial part of
      the total variation. Prior knowledge about the experimental variability allows
      for a correct design, a prerequisite for the detection of biologically
      significant disease-specific differential proteins in clinical proteomics
      experiments. 

PMID- 25775047
TI  - Bridging the gap between point-of-care testing and laboratory testing in
      hemostasis.
AB  - Point-of-care (POC) testing within hemostasis is an expanding field, with the
      most widely used test being POC international normalized ratio (INR). Many of
      these devices are being used in a nonlaboratory setting by staff with no
      laboratory training. In the United Kingdom, external quality assessment (EQA) is
      provided by the organization UK National External Quality Assessment Scheme for
      Blood Coagulation (UK NEQAS BC). Participants within the UK NEQAS BC POC INR
      program are largely based in primary care (77%), with the majority of EQA samples
      and patients tests being performed by nurses (70%). Many of these centers do not
      have support from the laboratory staff and may, therefore, not understand the
      requirement for a robust quality control (QC) system comprising both internal
      quality control (IQC) and EQA. From data acquired through a questionnaire of
      these UK NEQAS BC users, we observed that 2% of the centers never perform IQC
      tests, only 29% perform IQC tests when starting a new batch of test strips, and
      just 15% carry out IQC with each clinic as recommended by the UK guidelines. The
      imprecision of EQA tests was greater for POC users than in the UK NEQAS BC
      hospital laboratory program, with average coefficients of variation for a 2-year
      period of 11.0 and 7.3%, respectively. This may reflect the handling of EQA
      samples rather than the imprecision of the method, due to the lack of laboratory
      training amongst POC staff. POC INR in the UK could greatly benefit from more
      interaction and support from laboratories to these POC testers. 

PMID- 25775049
TI  - Holistic processing from learned attention to parts.
AB  - Attention helps us focus on what is most relevant to our goals, and prior work
      has shown that aspects of attention can be learned. Learned inattention to parts
      can abolish holistic processing of faces, but it is unknown whether learned
      attention to parts is sufficient to cause a change from part-based to holistic
      processing with objects. We trained subjects to individuate nonface objects
      (Greebles) from 2 categories: Ploks and Glips. Diagnostic information was in
      complementary halves for the 2 categories. Holistic processing was then tested
      with Plok-Glip composites that combined the kind of part that was diagnostic or
      nondiagnostic during training. Exposure to Greeble parts resulted in general
      failures of selective attention for nondiagnostic composites, but face-like
      holistic processing was only observed for diagnostic composites. These results
      demonstrated a novel link between learned attentional control and the acquisition
      of holistic processing.

PMID- 25775048
TI  - A targeted infection prevention intervention in nursing home residents with
      indwelling devices: a randomized clinical trial.
AB  - IMPORTANCE: Indwelling devices (eg, urinary catheters and feeding tubes) are
      often used in nursing homes (NHs). Inadequate care of residents with these
      devices contributes to high rates of multidrug-resistant organisms (MDROs) and
      device-related infections in NHs. OBJECTIVE: To test whether a multimodal
      targeted infection program (TIP) reduces the prevalence of MDROs and incident
      device-related infections. DESIGN, SETTING, AND PARTICIPANTS: Randomized clinical
      trial at 12 community-based NHs from May 2010 to April 2013. Participants were
      high-risk NH residents with urinary catheters, feeding tubes, or both.
      INTERVENTIONS: Multimodal, including preemptive barrier precautions, active
      surveillance for MDROs and infections, and NH staff education. MAIN OUTCOMES AND
      MEASURES: The primary outcome was the prevalence density rate of MDROs, defined
      as the total number of MDROs isolated per visit averaged over the duration of a
      resident's participation. Secondary outcomes included new MDRO acquisitions and
      new clinically defined device-associated infections. Data were analyzed using a
      mixed-effects multilevel Poisson regression model (primary outcome) and a Cox
      proportional hazards model (secondary outcome), adjusting for facility-level
      clustering and resident-level variables. RESULTS: In total, 418 NH residents with
      indwelling devices were enrolled, with 34,174 device-days and 6557 anatomic sites
      sampled. Intervention NHs had a decrease in the overall MDRO prevalence density
      (rate ratio, 0.77; 95% CI, 0.62-0.94). The rate of new methicillin-resistant
      Staphylococcus aureus acquisitions was lower in the intervention group than in
      the control group (rate ratio, 0.78; 95% CI, 0.64-0.96). Hazard ratios for the
      first and all (including recurrent) clinically defined catheter-associated
      urinary tract infections were 0.54 (95% CI, 0.30-0.97) and 0.69 (95% CI, 0.49
      0.99), respectively, in the intervention group and the control group. There were
      no reductions in new vancomycin-resistant enterococci or resistant gram-negative
      bacilli acquisitions or in new feeding tube-associated pneumonias or skin and
      soft-tissue infections. CONCLUSIONS AND RELEVANCE: Our multimodal TIP
      intervention reduced the overall MDRO prevalence density, new methicillin
      resistant S aureus acquisitions, and clinically defined catheter-associated
      urinary tract infection rates in high-risk NH residents with indwelling devices.
      Further studies are needed to evaluate the cost-effectiveness of this approach as
      well as its effects on the reduction of MDRO transmission to other residents, on
      the environment, and on referring hospitals. TRIAL REGISTRATION:
      clinicaltrials.gov Identifier: NCT01062841.

PMID- 25775050
TI  - Community-acquired pneumonia.
AB  - PURPOSE OF REVIEW: Community-acquired pneumonia (CAP) is the most common
      infectious disease cause of death. We summarize recent findings regarding the
      epidemiology of CAP in adults, efficacy of vaccines against Streptococcus
      pneumoniae, diagnostics, and discuss the current controversy between CAP and
      healthcare-associated pneumonia (HCAP). RECENT FINDINGS: The emergence of the
      Middle East respiratory syndrome coronavirus and the avian influenza A strain
      H7N9 are of concern but still these are infrequent causes of CAP. Recent data
      indicate that vaccinating children also protects adults against CAP by generating
      significant herd immunity, and that the conjugated pneumococcal vaccine in adults
      may offer some efficacy in preventing CAP caused by vaccine serotypes. The
      immunochromotagraphic urinary antigen test has improved the diagnostic yield for
      the aetiology of CAP, and initial data demonstrate that a novel multiplex urinary
      antigen test will further increase the sensitivity for detection of S.
      pneumoniae. There has been significant concern that a relatively recently
      described pneumonia category, HCAP, requires empirical treatment for potentially
      multidrug-resistant organisms (MDRO). However, new evidence shows that (at least
      in Europe) pneumonia caused by MDRO remains uncommon even in HCAP category
      patients. SUMMARY: CAP remains a major cause of morbidity and mortality. Advances
      in vaccination and diagnosis should help reduce the amount of disease due to S.
      pneumoniae, the commonest cause of CAP. Outside of the United States, MDRO are
      relatively uncommon causes of CAP, and the increased mortality of HCAP category
      patients seems to be related to their comorbidities and age rather than microbial
      aetiology.

PMID- 25775051
TI  - 7-Ketocholesterol increases retinal microglial migration, activation, and
      angiogenicity: a potential pathogenic mechanism underlying age-related macular
      degeneration.
AB  - Age-related macular degeneration (AMD) has been associated with both accumulation
      of lipid and lipid oxidative products, as well as increased neuroinflammatory
      changes and microglial activation in the outer retina. However, the relationships
      between these factors are incompletely understood. 7-Ketocholesterol (7KCh) is a
      cholesterol oxidation product localized to the outer retina with prominent pro
      inflammatory effects. To explore the potential relationship between 7KCh and
      microglial activation, we localized 7KCh and microglia to the outer retina of
      aged mice and investigated 7KCh effects on retinal microglia in both in vitro and
      in vivo systems. We found that retinal microglia demonstrated a prominent
      chemotropism to 7KCh and readily internalized 7KCh. Sublethal concentrations of
      7KCh resulted in microglial activation and polarization to a pro-inflammatory M1
      state via NLRP3 inflammasome activation. Microglia exposed to 7KCh reduced
      expression of neurotrophic growth factors but increased expression of angiogenic
      factors, transitioning to a more neurotoxic and pro-angiogenic phenotype.
      Finally, subretinal transplantation of 7KCh-exposed microglia promoted choroidal
      neovascularization (CNV) relative to control microglia in a Matrigel-CNV model.
      The interaction of retinal microglia with 7KCh in the aged retina may thus
      underlie how outer retinal lipid accumulation in intermediate AMD results in
      neuroinflammation that ultimately drives progression towards advanced AMD. 

PMID- 25775054
TI  - Polypoid endometriosis presenting as a mass at the pouch of Douglas.

PMID- 25775053
TI  - Local RNA flexibility perturbation of the IRES element induced by a novel ligand
      inhibits viral RNA translation.
AB  - The internal ribosome entry site (IRES) element located at the 5'untranslated
      genomic region of various RNA viruses mediates cap-independent initiation of
      translation. Picornavirus IRES activity is highly dependent on both its
      structural organization and its interaction with host factors. Small molecules
      able to interfere with RNA function are valuable candidates for antiviral agents.
      Here we show that a small molecule based on benzimidazole (IRAB) inhibited foot
      and-mouth disease virus (FMDV) IRES-dependent protein synthesis in cells
      transfected with infectious RNA leading to a decrease of the virus titer, which
      was higher than that induced by a structurally related benzimidazole derivative.
      Interestingly, IRAB preferentially inhibited IRES-dependent translation in cell
      free systems in a dose-dependent manner. RNA structural analysis by SHAPE
      demonstrated an increased local flexibility of the IRES structure upon incubation
      with IRAB, which affected 3 stem-loops (SL) of domain 3. Fluorescence binding
      assays conducted with individual aminopurine-labeled oligoribonucleotides
      indicated that the SL3A binds IRAB (EC50 18 MUM). Taken together, the results
      derived from SHAPE reactivity and fluorescence binding assays suggested that the
      target site of IRAB within the FMDV IRES might be a folded RNA structure that
      involves the entire apical region of domain 3. Our data suggest that the
      conformational changes induced by this compound on a specific region of the IRES
      structure which is essential for its activity is, at least in part, responsible
      for the reduced IRES efficiency observed in cell free lysates and, particularly,
      in RNA-transfected cells.

PMID- 25775052
TI  - Bivalirudin vs heparin with or without tirofiban during primary percutaneous
      coronary intervention in acute myocardial infarction: the BRIGHT randomized
      clinical trial.
AB  - IMPORTANCE: The safety and efficacy of bivalirudin compared with heparin with or
      without glycoprotein IIb/IIIa inhibitors in patients with acute myocardial
      infarction (AMI) undergoing primary percutaneous coronary intervention (PCI) are
      uncertain. OBJECTIVE: To determine if bivalirudin is superior to heparin alone
      and to heparin plus tirofiban during primary PCI. DESIGN, SETTING, AND
      PARTICIPANTS: Multicenter, open-label trial involving 2194 patients with AMI
      undergoing primary PCI at 82 centers in China between August 2012 and June 2013.
      INTERVENTIONS: Patients were randomly assigned to receive bivalirudin with a post
      PCI infusion (n = 735), heparin alone (n = 729), or heparin plus tirofiban with a
      post-PCI infusion (n = 730). Among patients treated with bivalirudin, a
      postprocedure 1.75 mg/kg/h infusion was administered for a median of 180 minutes
      (IQR, 148-240 minutes). MAIN OUTCOMES AND MEASURES: The primary end point was 30
      day net adverse clinical events, a composite of major adverse cardiac or cerebral
      events (all-cause death, reinfarction, ischemia-driven target vessel
      revascularization, or stroke) or bleeding. Additional prespecified safety end
      points included the rates of acquired thrombocytopenia at 30 days, and stent
      thrombosis at 30 days and 1 year. RESULTS: Net adverse clinical events at 30 days
      occurred in 65 patients (8.8%) of 735 who were treated with bivalirudin compared
      with 96 patients (13.2%) of 729 treated with heparin (relative risk [RR], 0.67;
      95% CI, 0.50-0.90; difference, -4.3%, 95% CI, -7.5% to -1.1%; P = .008); and 124
      patients (17.0%) of 730 treated with heparin plus tirofiban (RR for bivalirudin
      vs heparin plus tirofiban, 0.52; 95% CI, 0.39-0.69; difference, -8.1%, 95% CI, 
      11.6% to -4.7%; P < .001). The 30-day bleeding rate was 4.1% for bivalirudin,
      7.5% for heparin, and 12.3% for heparin plus tirofiban (P < .001). There were no
      statistically significant differences between treatments in the 30-day rates of
      major adverse cardiac or cerebral events (5.0% for bivalirudin, 5.8% for heparin,
      and 4.9% for heparin plus tirofiban, P = .74), stent thrombosis (0.6% vs 0.9% vs
      0.7%, respectively, P = .77), acquired thrombocytopenia (0.1% vs 0.7% vs 1.1%; P
      = .07), or in acute (<24-hour) stent thrombosis (0.3% in each group). At the 1
      year follow-up, the results remained similar. CONCLUSIONS AND RELEVANCE: Among
      patients with AMI undergoing primary PCI, the use of bivalirudin with a median 3
      hour postprocedure PCI-dose infusion resulted in a decrease in net adverse
      clinical events compared with both heparin alone and heparin plus tirofiban. This
      finding was primarily due to a reduction in bleeding events with bivalirudin,
      without significant differences in major adverse cardiac or cerebral events or
      stent thrombosis. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01696110.

PMID- 25775055
TI  - Effects of 2.4 GHz radiofrequency radiation emitted from Wi-Fi equipment on
      microRNA expression in brain tissue.
AB  - PURPOSE: MicroRNAs (miRNA) play a paramount role in growth, differentiation,
      proliferation and cell death by suppressing one or more target genes. However,
      their interaction with radiofrequencies is still unknown. The aim of this study
      was to investigate the long-term effects of radiofrequency radiation emitted from
      a Wireless Fidelity (Wi-Fi) system on some of the miRNA in brain tissue.
      MATERIALS AND METHODS: The study was carried out on 16 Wistar Albino adult male
      rats by dividing them into two groups such as sham (n = 8) and exposure (n = 8).
      Rats in the exposure group were exposed to 2.4 GHz radiofrequency (RF) radiation
      for 24 hours a day for 12 months (one year). The same procedure was applied to
      the rats in the sham group except the Wi-Fi system was turned off. Immediately
      after the last exposure, rats were sacrificed and their brains were removed. miR
      9-5p, miR-29a-3p, miR-106b-5p, miR-107, miR-125a-3p in brain were investigated in
      detail. RESULTS: The results revealed that long-term exposure of 2.4 GHz Wi-Fi
      radiation can alter expression of some of the miRNAs such as miR-106b-5p (adj p*
      = 0.010) and miR-107 (adj p* = 0.005). We observed that mir 107 expression is 3.3
      times and miR- 106b-5p expression is 3.65 times lower in the exposure group than
      in the control group. However, miR-9-5p, miR-29a-3p and miR-125a-3p levels in
      brain were not altered. CONCLUSION: Long-term exposure of 2.4 GHz RF may lead to
      adverse effects such as neurodegenerative diseases originated from the alteration
      of some miRNA expression and more studies should be devoted to the effects of RF
      radiation on miRNA expression levels.

PMID- 25775057
TI  - Reply to Letter: "Utilization of Small Pediatric Donors Including Infants for
      Pancreas and Kidney Transplantation: Exemplification of the Surgical Technique
      and Surveillance".

PMID- 25775058
TI  - Improving Escalation of Care: Development and Validation of the Quality of
      Information Transfer Tool.
AB  - OBJECTIVE: To develop and provide validity and feasibility evidence for the
      QUality of Information Transfer (QUIT) tool. BACKGROUND: Prompt escalation of
      care in the setting of patient deterioration can prevent further harm. Escalation
      and information transfer skills are not currently measured in surgery. METHODS:
      This study comprised 3 phases: the development (phase 1), validation (phase 2),
      and feasibility analysis (phase 3) of the QUIT tool. Phase 1 involved
      identification of core skills needed for successful escalation of care through
      literature review and 33 semistructured interviews with stakeholders. Phase 2
      involved the generation of validity evidence for the tool using a simulated
      setting. Thirty surgeons assessed a deteriorating postoperative patient in a
      simulated ward and escalated their care to a senior colleague. The face and
      content validity were assessed using a survey. Construct and concurrent validity
      of the tool were determined by comparing performance scores using the QUIT tool
      with those measured using the Situation-Background-Assessment-Recommendation
      (SBAR) tool. Phase 3 was conducted using direct observation of escalation
      scenarios on surgical wards in 2 hospitals. RESULTS: A 7-category assessment tool
      was developed from phase 1 consisting of 24 items. Twenty-one of 24 items had
      excellent content validity (content validity index >0.8). All 7 categories and 18
      of 24 (P < 0.05) items demonstrated construct validity. The correlation between
      the QUIT and SBAR tools used was strong indicating concurrent validity (r =
      0.694, P < 0.001). Real-time scoring of escalation referrals was feasible and
      indicated that doctors currently have better information transfer skills than
      nurses when faced with a deteriorating patient. CONCLUSIONS: A validated tool to
      assess information transfer for deteriorating surgical patients was developed and
      tested using simulation and real-time clinical scenarios. It may improve the
      quality and safety of patient care on the surgical ward.

PMID- 25775060
TI  - Commentary on "Better Survival But Changing Causes of Death in Patients With
      Multiple Endocrine Neoplasia Type 1".

PMID- 25775059
TI  - Influence of Health Insurance Expansion on Disparities in the Treatment of Acute
      Cholecystitis.
AB  - OBJECTIVE: To evaluate the impact of the 2006 Massachusetts (MA) health reform on
      disparities in the management of acute cholecystitis (AC). BACKGROUND: Immediate
      cholecystectomy has been shown to be the optimal treatment for AC, yet variation
      in care persists depending upon insurance status and patient race. How increased
      insurance coverage impacts these disparities in surgical care is not known.
      METHODS: A cohort study of patients admitted with AC in MA and 3 control states
      from 2001 through 2009 was performed using the Hospital Cost and Utilization
      Project State Inpatient Databases. We examined all nonelderly white, black, or
      Latino patients by insurance type and patient race, evaluating changes in the
      probability of undergoing immediate cholecystectomy and disparities in receiving
      immediate cholecystectomy before and after Massachusetts health reform. RESULTS:
      Data from 141,344 patients hospitalized for AC were analyzed. Before the 2006
      reform, government-subsidized/self-pay (GS/SP) patients had a 6.6 to 9.9
      percentage-point lower (P < 0.001) probability of immediate cholecystectomy in
      both MA control states. The MA insurance expansion was independently associated
      with a 2.5 percentage-point increased probability of immediate cholecystectomy
      for all GS/SP patients in MA (P = 0.049) and a 5.0 percentage-point increased
      probability (P = 0.011) for nonwhite, GS/SP patients compared to control states.
      Racial disparities in the probability of immediate cholecystectomy seen before
      health care reform were no longer statistically significant after reform in MA
      while persisting in control states. CONCLUSIONS: The MA health reform was
      associated with increased probability of undergoing immediate cholecystectomy for
      AC and reduced disparities in undergoing cholecystectomy by insurance status and
      patient race.

PMID- 25775061
TI  - Attenuation of Postoperative Acute Liver Failure by Mesenchymal Stem Cell
      Treatment Due to Metabolic Implications.
AB  - OBJECTIVE: To prevent posthepatectomy acute liver failure after extended
      resection by treatment with mesenchymal stem cells (MSCs). BACKGROUND: Liver
      tumors often require extended liver resection, overburdening metabolic and
      regenerative capacities of the remnant organ. Resulting dysfunction and failure
      may be improved by the proregenerative characteristics of MSCs. METHODS: Extended
      liver resection was performed in (DPPIV)-deficient F344-Fischer rats. Wild-type
      animals served as donors of peritoneal adipose-derived MSCs. These were
      predifferentiated in vitro into hepatocytic cells and delivered to the liver by
      splenic application. Liver-related blood parameters (international normalized
      ratio, bilirubin, aspartate aminotransferase, alanine aminotransferase) and liver
      histology (hematoxylin-eosin, Sudan III) were determined to monitor liver
      function. Metabolic changes were assessed by metabolomic analyses in the remnant
      liver and the serum. Liver damage and regeneration were quantified by
      determination of the apoptotic and proliferation rates. RESULTS: MSCs supported
      survival after partial hepatectomy. They decreased liver-related blood parameters
      indicative for the improvement of liver function. The extensive lipid
      accumulation in hepatocytes illustrating the metabolic overload after resection
      was attenuated. Treatment with MSCs normalized imbalance of amino acids,
      acylcarnitines, sphingolipids, and glycerophospholipids in the liver and blood.
      Furthermore, MSCs decreased the apoptotic rate and increased the proliferation
      rate. The experimental time period (48 hours) was too short to allow for
      integration of MSCs into the host liver. Thus, the mode of action was probably
      indirect. CONCLUSIONS: MSCs ameliorated hepatic dysfunction and improved liver
      regeneration after extended resection by paracrine mechanisms. They may represent
      a new therapeutic option to treat posthepatectomy acute liver failure.

PMID- 25775062
TI  - Surgical Resection Versus Radiofrequency Ablation for Single Hepatocellular
      Carcinoma <= 2  cm in a Propensity Score Model.
AB  - OBJECTIVES: To evaluate the efficacy of surgical resection (SR) and
      radiofrequency ablation (RFA) for single hepatocellular carcinoma (HCC) 2  cm or
      less. BACKGROUND: The optimal management for Barcelona Clinic Liver Cancer (BCLC)
      very early-stage HCC is undetermined. METHODS: Between 2002 and 2013, a total of
      237 (SR, 109; RFA, 128) patients with BCLC very early-stage HCC were enrolled.
      Their overall survival (OS) and recurrence-free survival (RFS) were compared.
      Propensity score matching analysis identified 79 matched pairs of patients to
      compare outcomes. RESULTS: At baseline, patients with SR were younger and had
      larger tumors (both P < 0.05). The 5-year OS rates were 81% versus 76% (P =
      0.136), whereas 5-year RFS rates were 49% versus 24% (P < 0.001) for SR and RFA
      groups, respectively. In the propensity model, the baseline variables were well
      balanced between 2 groups. Surgical resection was significantly associated with
      better OS and RFS compared with RFA; the 5-year OS rates were 80% versus 66% (P =
      0.034), and 5-year RFS rates were 48% versus 18% (P < 0.001) for SR and RFA
      groups, respectively. The Cox proportional hazards model identified RFA as an
      independent predictor for mortality and tumor recurrence in the propensity model
      (hazard ratio, 2.120 and 2.421, respectively; both P < 0.05). Patients with
      recurrent HCC had inferior prognosis compared with patients without recurrence (P
      = 0.001). However, the survival after recurrence was similar between patients
      initially treated with SR or RFA (P = 0.415). CONCLUSIONS: Surgical resection
      provides better long-term OS and RFS compared with RFA in patients with BCLC very
      early-stage HCC. Surgical resection should be considered as the first-line
      treatment for these patients.

PMID- 25775063
TI  - Surgical Checklist Implementation Project: The Impact of Variable WHO Checklist
      Compliance on Risk-adjusted Clinical Outcomes After National Implementation: A
      Longitudinal Study.
AB  - OBJECTIVE: To evaluate impact of WHO checklist compliance on risk-adjusted
      clinical outcomes, including the influence of checklist components (Sign-in, Time
      out, Sign-out) on outcomes. BACKGROUND: There remain unanswered questions
      surrounding surgical checklists as a quality and safety tool, such as the impact
      in cases of differing complexity and the extent of checklist implementation.
      METHODS: Data were collected from surgical admissions (6714 patients) from March
      2010 to June 2011 at 5 academic and community hospitals. The primary endpoint was
      any complication, including mortality, occurring before hospital discharge.
      Checklist usage was recorded as checklist completed in full/partly. Multilevel
      modeling was performed to investigate the association between
      complications/mortality and checklist completion. RESULTS: Significant
      variability in checklist usage was found: although at least 1 of the 3 components
      was completed in 96.7% of cases, the entire checklist was only completed in 62.1%
      of cases. Checklist completion did not affect mortality reduction, but
      significantly lowered risk of postoperative complication (16.9% vs. 11.2%), and
      was largely noticed when all 3 components of the checklist had been completed
      (odds ratio = 0.57, 95% confidence interval: 0.37-0.87, P < 0.01). Calculated
      population-attributable fractions showed that 14% (95% confidence interval: 7%
      21%) of the complications could be prevented if full completion of the checklist
      was implemented. CONCLUSIONS: Checklist implementation was associated with
      reduced case-mix-adjusted complications after surgery and was most significant
      when all 3 components of the checklist were completed. Full, as opposed to
      partial, checklist completion provides a health policy opportunity to improve
      checklist impact on surgical safety and quality of care.

PMID- 25775064
TI  - Localization of the Sentinel Lymph Node in Melanoma Without Blue Dye.
AB  - OBJECTIVE: The purpose of this study was to assess regional recurrence rates of
      patients who underwent sentinel lymph node biopsy (SLNB) using radiocolloid
      guidance alone. BACKGROUND: Isosulfan blue dye is commonly used along with Tc99
      labeled radiocolloid localization in SLNB for melanoma. Blue dye has, however,
      been associated with allergic reactions, long-term staining of skin, and
      increased cost. We hypothesized that the rate of regional recurrence when SLNB is
      performed with radiocolloid alone would be comparable to established reports
      using both radiocolloid and blue dye. METHODS: A prospectively collected database
      was retrospectively queried for patients who underwent SLNB for melanoma during
      the years 2005 through 2008. Data collected included patient demographics,
      primary lesion characteristics, operative details, and recurrence. The primary
      outcome was the rate of recurrence within the biopsied basin after negative
      SLNB's performed without isosulfan blue dye. RESULTS: In 215 patients, 279 nodal
      basins were identified. All patients underwent successful radiocolloid
      localization, and positive sentinel nodes were found in 40 patients (18.6%). Six
      of 175 patients with a negative SLNB developed a regional node recurrence as the
      first site of metastasis (3.4%). Among all 215 patients, 44 experienced
      recurrence of any kind (20.5%). Higher mitotic rate and Breslow depth were
      significantly associated with likelihood of recurrence. CONCLUSIONS: Success
      rates, node positivity rates, and rates of regional recurrence after SLNB for
      melanoma using radiocolloid alone are acceptable and similar to those of prior
      reports using blue dye plus radiocolloid.

PMID- 25775065
TI  - Tracheobronchial Necrosis After Caustic Ingestion.
AB  - OBJECTIVE: The aim of this study was to describe the management and outcome of
      tracheobronchial necrosis (TBN) after caustic ingestion. BACKGROUND: Emergency
      pulmonary patch repair has been reported to be lifesaving in patients with
      caustic TBN. METHODS: Patients who underwent management of caustic TBN between
      1989 and 2013, were included. TBN was defined as early if present on admission
      and late if occurring thereafter. Operative outcomes, long-term survival, and
      functional outcomes were compared with those of 269 patients without TBN who
      underwent esophagectomy for caustic injuries. RESULTS: Twenty patients were
      included (10 men; median age = 39 years). Early TBN was detected in 14 patients,
      and late TBN occurred in 7 patients, 8 days (range:: 6-10 days) after admission.
      TBN involved the left bronchus (n = 17; 85%), the carina (n = 10; 50%), the
      supracarinal trachea (n = 9; 45%), the right bronchus (n = 4; 20%), and the
      cervical trachea (n = 3; 15%). Seventeen patients underwent esophagogastrectomy,
      2 underwent esophagectomy, and in 1 patient, resection was eventually abandoned.
      Pulmonary patch repair was performed in 16 patients (80%). Nine patients (45%)
      died and morbidity was 100%. In univariate analysis, late TBN (P = 0.017) and
      acid ingestion (P = 0.002) were predictors of mortality. All survivors underwent
      restoring colopharyngoplasty. Five-year survival (28%) and functional success
      (25%) rates were significantly impaired when compared with esophagectomy patients
      without TBN. CONCLUSIONS: TBN is one of the most devastating complications of
      caustic ingestion. Pulmonary patch repair is technically simple and can be
      lifesaving in this difficult situation.

PMID- 25775067
TI  - Survival Benefit of Adjuvant Chemoradiotherapy in Patients With Ampulla of Vater
      Cancer: A Systematic Review and Meta-analysis.
AB  - OBJECTIVE: We conducted a systematic review and meta-analysis focusing on the
      impact of adjuvant radiotherapy (RT) on overall survival (OS) in ampulla of Vater
      (AoV) cancer. BACKGROUND: The adjuvant treatment for AoV cancer is a subject of
      controversy without convincing evidence from randomized study. METHODS: A
      comprehensive search was performed in the databases of EMBASE, PubMed, Web of
      Science, Cochrane Library, and Ovid from inception to July 2014. We included
      studies, which compared survival between patients with or without adjuvant RT
      after curative surgery solely for AoV cancer. Hazard ratio (HR) for OS was
      extracted, and a random-effects model was used for pooled analysis. RESULTS: Ten
      retrospective studies including 3361 patients met all inclusion criteria and were
      included for the final meta-analysis. Adjuvant RT was delivered with concurrent
      chemotherapy, mostly 5-fluorouracil, in all institutional studies. Generally,
      adjuvant RT groups included more patients with locally advanced disease or lymph
      node metastasis than did the surgery alone groups. The pooled results
      demonstrated that adjuvant RT significantly reduced the risk of death (HR = 0.75;
      P = 0.01). Exploratory analyses showed that patients with lymph node metastasis
      (HR = 0.52; P = 0.001) and locally advanced disease (HR = 0.42; P = 0.001) may
      also have survival benefit from adjuvant RT. No clear evidence of publication
      bias was found. CONCLUSIONS: This is the first meta-analysis evaluating the role
      of adjuvant RT in AoV cancer. Our results suggest the potential for survival
      benefit of adjuvant chemoradiotherapy. Further studies, preferably randomized
      clinical trials, are needed to confirm our results.

PMID- 25775068
TI  - Parenchymal-sparing Hepatectomy in Colorectal Liver Metastasis Improves
      Salvageability and Survival.
AB  - OBJECTIVE: To investigate prognostic impact of parenchymal-sparing hepatectomy
      (PSH) for solitary small colorectal liver metastasis (CLM). BACKGROUND: It is
      unclear whether PSH confers an oncologic benefit through increased salvageability
      or is a detriment through increasing recurrence rate. METHODS: Database of 300
      CLM patients with a solitary tumor (<= 30 mm in size) was reviewed from 1993 to
      2013. A total of 156 patients underwent PSH and 144 patients underwent right
      hepatectomy, left hepatectomy, or left lateral sectionectomy (non-PSH group).
      RESULTS: The rate of PSH increased over the study period (P < 0.01). PSH did not
      impact negatively on overall (OS), recurrence-free, and liver-only recurrence
      free survival, compared with non-PSH (P = 0.53, P = 0.97, and P = 0.69,
      respectively). Liver-only recurrence was observed in 22 patients (14%) in the PSH
      and 25 (17%) in the non-PSH group (P = 0.44). Repeat hepatectomy was more
      frequently performed in the PSH group (68% vs 24%, P < 0.01). Subanalysis of
      patients with liver-only recurrence revealed better 5-year overall survival from
      initial hepatectomy and from liver recurrence in the PSH than in the non-PSH
      group [72.4% vs 47.2% (P = 0.047) and 73.6% vs 30.1% (P = 0.018), respectively].
      Multivariate analysis revealed that non-PSH was a risk of noncandidacy for repeat
      hepatectomy (hazard ratio: 8.18, confidence interval: 1.89-45.7, P < 0.01).
      CONCLUSIONS: PSH did not increase recurrence in the liver remnant but more
      importantly improved 5-year survival in case of recurrence (salvageability). PSH
      should be the standard approach to CLM to allow for salvage surgery in case of
      liver recurrence.

PMID- 25775069
TI  - Interferon-based Adjuvant Chemoradiation for Resected Pancreatic Head Cancer:
      Long-term Follow-up of the Virginia Mason Protocol.
AB  - OBJECTIVE: To report the long-term impact of adjuvant interferon-based
      chemoradiation therapy (IFN-CRT) after pancreaticoduodenectomy (PD) for
      pancreatic adenocarcinoma (PDAC). BACKGROUND: In 2003, we reported an actuarial 5
      year overall survival (OS) of 55% (22 months median follow-up) using adjuvant IFN
      CRT after PD. As the original cohort is now 10 years distant from PD, we sought
      to examine their actual survival, describe patterns of recurrence, and determine
      prognostic factors. METHODS: From 1995 to 2002, 43 patients underwent PD for PDAC
      and received adjuvant IFN-CRT consisting of external-beam irradiation, continuous
      5-fluorouracil infusion, weekly intravenous bolus cisplatin, and subcutaneous
      interferon-alpha. Survival was calculated by the method of Kaplan and Meier, and
      prognostic factors were compared using a log-rank test and a Cox proportional
      hazards model. RESULTS: With all patients at least 10 years from PD, the 5-year
      actual survival was 42% and 10-year actual survival was 28% with median OS of 42
      months (95% confidence interval: 22-110 months). Nine patients survived beyond 10
      years with 7 currently alive without evidence of disease. Initial recurrence
      included 4 local, 17 distant, and 4 combined sites at a median of 25 months. IFN
      CRT was interrupted in 70% of patients because of grade 3 or 4 toxicity, whereas
      42% of patients required hospitalization. Adverse prognostic factors included
      lymph node ratio of 50% or more, Eastern Cooperative Oncology Group performance
      status of 1 or higher, and IFN-CRT treatment interruption. CONCLUSIONS: Adjuvant
      IFN-CRT after PD can provide long-term survival in resected PDAC. Further studies
      should focus on patient and tumor factors to maximize benefit and minimize
      toxicity.

PMID- 25775070
TI  - Current Surgical Management of Pediatric Idiopathic Constipation: A Systematic
      Review of Published Studies.
AB  - OBJECTIVE: Surgery for pediatric idiopathic constipation (IC) is undertaken after
      failure of bowel management programs. Decisions are influenced by rectal biopsy,
      transit studies, megacolon/megarectum, degree of soiling/incontinence, and
      anorectal manometry profile(s). A systematic review of ALL published studies
      critically evaluates outcomes of surgery for IC. METHODS: MEDLINE (PubMed),
      Google Scholar, and EMBase were searched for English-language articles only.
      Studies included (1) peer-review publications with 3 or more patients, and (2)
      clinical outcomes defined by authors. RESULTS: Forty-five reports (1157 patients)
      met full inclusion criteria. Only 2 papers were randomized controlled trials.
      Many had small patient numbers (median n = 16; range: 3-114). Twenty-three
      described heterogenous populations with variant pathology. Follow-up was short
      (median = 1.5 years: range: 3 months-14 years). The antegrade continence enema
      operation (ACE)-[open/laparoscopic assisted, cecostomy, or "left sided" ACE]-was
      judged as successful in 82% of cases, although high morbidity and reoperations
      were reported. Colon resection and pull through operations had "good" outcome(s)
      in 79% of children with 17% reporting significant morbidity and a 10% incidence
      of revisional surgery. Anal dilatation did not improve outcome(s). Botulinum
      toxin injection scored equally effective compared to internal sphincter myectomy
      in short-term follow-up. Permanent colostomy was considered successful in 86% of
      refractory IC cases. CONCLUSIONS: Surgical management and outcome(s) for
      pediatric IC are based on low-quality evidence. No single operation was
      considered "best practice." This study crucially highlights that surgeons must
      develop better care strategies.

PMID- 25775071
TI  - Predicting Success of Catheter Drainage in Infected Necrotizing Pancreatitis.
AB  - INTRODUCTION: At least 30% of patients with infected necrotizing pancreatitis are
      successfully treated with catheter drainage alone. It is currently not possible
      to predict which patients also need necrosectomy. We evaluated predictive factors
      for successful catheter drainage. METHODS: This was a post hoc analysis of 130
      prospectively included patients undergoing catheter drainage for (suspected)
      infected necrotizing pancreatitis. Using logistic regression, we evaluated the
      association between success of catheter drainage (ie, survival without
      necrosectomy) and 22 factors regarding demographics, disease severity (eg, Acute
      Physiology And Chronic Health Evaluation II score, organ failure), and
      morphologic characteristics on computed tomography (eg, percentage of necrosis).
      RESULTS: Catheter drainage was performed percutaneously in 113 patients and
      endoscopically in 17 patients. Infected necrosis was confirmed in 116 patients
      (89%). Catheter drainage was successful in 45 patients (35%). In multivariable
      regression, the following factors were associated with a reduced chance of
      success: male sex [odds ratio (OR) = 0.27; 95% confidence interval (CI): 0.09
      0.55; P <0.01), multiple organ failure (OR = 0.15; 95% CI: 0.04-0.62; P < 0.01),
      percentage of pancreatic necrosis (<30%/30%-50%/>50%: OR = 0.54; 95% CI: 0.30
      0.96; P = 0.03), and heterogeneous collection (OR = 0.21; 95% CI: 0.06-0.67; P <
      0.01). A prediction model incorporating these factors demonstrated an area under
      the receiver operating characteristic curve of 0.76. A prognostic nomogram
      yielded success probability of catheter drainage from 2% to 91%. CONCLUSIONS:
      Male sex, multiple organ failure, increasing percentage of pancreatic necrosis
      and heterogeneity of the collection are negative predictors for success of
      catheter drainage in infected necrotizing pancreatitis. The constructed nomogram
      can guide prognostication in clinical practice and risk stratification in
      clinical studies.

PMID- 25775066
TI  - Pathologic Evaluation and Reporting of Intraductal Papillary Mucinous Neoplasms
      of the Pancreas and Other Tumoral Intraepithelial Neoplasms of Pancreatobiliary
      Tract: Recommendations of Verona Consensus Meeting.
AB  - BACKGROUND: There are no established guidelines for pathologic
      diagnosis/reporting of intraductal papillary mucinous neoplasms (IPMNs). DESIGN:
      An international multidisciplinary group, brought together by the Verona Pancreas
      Group in Italy-2013, was tasked to devise recommendations. RESULTS: (1) Crucial
      to rule out invasive carcinoma with extensive (if not complete) sampling. (2)
      Invasive component is to be documented in a full synoptic report including its
      size, type, grade, and stage. (3) The term "minimally invasive" should be
      avoided; instead, invasion size with stage and substaging of T1 (1a, b, c; <=
      0.5, > 0.5-<= 1, > 1 cm) is to be documented. (4) Largest diameter of the
      invasion, not the distance from the nearest duct, is to be used. (5) A category
      of "indeterminate/(suspicious) for invasion" is acceptable for rare cases. (6)
      The term "malignant" IPMN should be avoided. (7) The highest grade of dysplasia
      in the non-invasive component is to be documented separately. (8) Lesion size is
      to be correlated with imaging findings in cysts with rupture. (9) The main duct
      diameter and, if possible, its involvement are to be documented; however, it is
      not required to provide main versus branch duct classification in the resected
      tumor. (10) Subtyping as gastric/intestinal/pancreatobiliary/oncocytic/mixed is
      of value. (11) Frozen section is to be performed highly selectively, with
      appreciation of its shortcomings. (12) These principles also apply to other
      similar tumoral intraepithelial neoplasms (mucinous cystic neoplasms, intra
      ampullary, and intra-biliary/cholecystic). CONCLUSIONS: These recommendations
      will ensure proper communication of salient tumor characteristics to the
      management teams, accurate comparison of data between analyses, and development
      of more effective management algorithms.

PMID- 25775072
TI  - Laparoscopic Surgery or Conservative Treatment for Appendiceal Abscess in Adults?
      A Randomized Controlled Trial.
AB  - OBJECTIVE: We hypothesized that immediate laparoscopic surgery for appendiceal
      abscess would result in faster recovery than conservative treatment. BACKGROUND:
      On the basis of the retrospective studies, conservative management of appendiceal
      abscess is recommended as a first line treatment, but some controversy exists.
      METHODS: Sixty adult patients diagnosed with appendiceal abscess were randomly
      assigned to either laparoscopic surgery (n = 30) or conservative treatment (n =
      30). Hospital stay, recurrences, additional interventions, and complications
      within 60 days from randomization were recorded. RESULTS: There was no difference
      in hospital stay: 4 days (interquartile range: 3-5 days) in the laparoscopy group
      versus 5 days (3-8) in the conservative group, P = 0.105. Patients in the
      laparoscopy group had 10% risk for bowel resection and 13% risk for incomplete
      appendectomy. There were significantly fewer patients with unplanned readmissions
      in the laparoscopy group: 1 (3%) versus 8 (27%), P = 0.026. Additional
      interventions were required in 2 (7%) patients in the laparoscopy group
      (percutaneous drainage) and in 9 (30%) patients in the conservative group
      (surgery), P = 0.042. Recurrent abscesses and failure to respond to conservative
      treatment were the main reasons for additional interventions. Open surgery was
      required in 3 (10%) patients in the laparoscopy group and in 4 (13%) patients in
      the conservative group. Postoperative complications occurred in 3 patients in
      laparoscopic group versus 2 patients in the conservative group. The rate of
      uneventful recovery was 90% in the laparoscopy group versus 50% in the
      conservative group, P = 0.002. CONCLUSIONS: Laparoscopic surgery in experienced
      hands is safe and feasible first-line treatment for appendiceal abscess. It is
      associated with fewer readmissions and fewer additional interventions than
      conservative treatment with comparable hospital stay.

PMID- 25775073
TI  - Structured Training to Improve Nontechnical Performance of Junior Surgical
      Residents in the Operating Room: A Randomized Controlled Trial.
AB  - OBJECTIVE: The objective of the study was to evaluate the effectiveness of
      structured training on junior trainees' nontechnical performance in an operating
      room (OR) environment. BACKGROUND: Nontechnical skills (NTS) have been identified
      as critical competencies of surgeons in the OR, and regulatory bodies have
      mandated their integration in postgraduate surgical curricula. Strong evidence
      supporting the effectiveness of curricular NTS training, however, is lacking.
      METHODS: Junior surgical residents were randomized to receive either conventional
      residency training or additional NTS training in a 2-month curriculum. Learning
      was assessed through a knowledge quiz and an attitudes survey. Nontechnical
      performance was evaluated by blinded assessment of standardized OR crisis
      simulations at baseline (BL) and posttraining (PT) using the Nontechnical Skills
      for Surgeons (NOTSS) and Objective Structured Assessment of Nontechnical Skills
      (OSANTS) rating systems. Results are reported as median (interquartile ranges).
      RESULTS: Of 23 participants, 22 completed BL and PT assessments. Groups were
      equal at BL. At PT, curriculum-trained residents (n = 11) scored higher than
      conventionally trained residents (n = 11) in knowledge [12 (11-13) vs 8 (6-10), P
      < 0.001] and attitudes [4.58 (4.37-4.73) vs 4.20 (4.00-4.50), P = 0.008] about
      NTS. In a simulated OR, nontechnical performance of curriculum-trained residents
      improved significantly from BL to PT [NOTSS: 10 (7-11) vs 13 (10-15), P = 0.012;
      OSANTS: 23 (17-28) vs 31 (25-33), P = 0.012] whereas conventionally trained
      residents did not improve [NOTSS: 10 (10-13) vs 11 (9-14), P = 1.00; OSANTS: 26
      (24-32) vs 24 (23-32), P = 0.713]. CONCLUSIONS: The results demonstrate the
      effectiveness of structured curricular training in improving nontechnical
      performance in the first year of surgical residency, supporting routine
      implementation of nontechnical components in postgraduate surgical curricula.

PMID- 25775074
TI  - Laparoscopic Lavage for Hinchey III Diverticulitis-But to Whom?

PMID- 25775075
TI  - Procedure Delegation by Attending Surgeons Performing Concurrent Operations in
      Academic Medical Centers: Balancing Safety and Efficiency.

PMID- 25775076
TI  - Bile duct preserving surgery for hepatocellular carcinoma with bile duct tumor
      thrombus.

PMID- 25775077
TI  - Peeling-off technique or bile duct resection of tumor thrombus in hepatocellular
      carcinoma: does future liver-directed treatment justify less extensive surgery?

PMID- 25775078
TI  - Life experiences in active addiction and in recovery among treated and untreated
      persons: a national study.
AB  - Addiction treatment can be effective but fewer than 50% of addiction affected
      persons are ever treated. Little is known about the addiction and recovery
      experience of this large subgroup. A national sample of persons in recovery (N =
      3,176, 29.5% untreated) was used to begin addressing these questions to inform
      strategies to encourage help-seeking and to contribute to the small knowledge
      base on untreated individuals. Study domains were finances, family, social and
      civic functioning, health, criminal justice involvement, and employment. Treated
      persons reported significantly greater levels of negative-and fewer positive
      experiences in all areas during active addiction than did the untreated group.
      This gap was significantly narrowed in recovery. 

PMID- 25775079
TI  - Correlating Li/O2 cell capacity and product morphology with discharge current.
AB  - The discharge rate is critical to the performance of lithium/oxygen batteries: it
      impacts both cell capacity and discharge-phase morphology, and in so doing may
      also affect the efficiency of the oxygen-evolution reaction during recharging.
      First-discharge data from tens of Li/O2 cells discharged across four rates are
      analyzed statistically to inform these connections. In the practically
      significant superficial current-density range of 0.1 to 1 mA cm(-2), capacity is
      found to fall as a power law, with a Peukert's-law exponent of 1.6 +/- 0.1. X-ray
      diffractometry confirms the dominant presence of crystalline Li2O2 in the
      discharged electrodes. A completely air-free sample-transfer technique was
      developed to implement scanning electron microscopy (SEM) of the discharge
      product. SEM imaging of electrodes with near-average capacities provides
      statistically significant measures of the shape and size variation of
      electrodeposited Li2O2 particles with respect to discharge current. At lower
      rates, typical "toroidal" particles are observed that are well approximated as
      cylindrical structures, whose average radii remain relatively constant as
      discharge rate increases, whereas their average heights decrease. At the highest
      rate studied, air-free SEM shows that particles take needle-like shapes rather
      than forming the nanosheets or compact films described elsewhere. Average
      particle volumes decrease with current while particle surface-to-volume ratios
      increase dramatically, supporting the notion that Li2O2 grows by a locally mass
      transfer-limited nucleation and growth mechanism. 

PMID- 25775080
TI  - Adverse effects of obesity and/or high-fat diet on oocyte quality and metabolism
      are not reversible with resumption of regular diet in mice.
AB  - Obesity adversely affects reproduction and results in oocyte defects in both mice
      and humans. In the present study we used a mouse model to examine whether the
      adverse effects of an obesogenic diet on oocyte metabolism and morphology can be
      reversed by return to a control diet. The intervention group consisted of
      C57BL6/J mice placed on a high-fat diet (HFD; 35.8% fat and 20.2% protein by
      nutritional content) for 6 weeks and then switched to an isocaloric control diet
      (CD; 13% fat and 25% protein) for 8 weeks (HFD/CD mice). The control group
      consisted of age-matched C57BL6/J mice maintained on CD for 14 weeks (CD/CD
      mice). Although metabolic parameters (weight, glucose tolerance and cholesterol
      levels) of HFD/CD mice returned to normal after this 'diet reversal' period,
      several oocyte defects were not reversible. These HFD/CD oocytes demonstrated
      significantly higher percentages of abnormal meiotic spindles, lower
      mitochondrial membrane potential and lower ATP and citrate levels, and higher
      percentages of abnormal lipid accumulation and mitochondrial distribution
      compared with CD/CD mice. These results suggest that the negative effects of an
      obesogenic diet on oocyte quality are not reversible, despite reversal of
      metabolic parameters. These data may provide better insight when counselling
      obese women regarding reproductive options and success. 

PMID- 25775081
TI  - Development of the shape bias during the second year.
AB  - The shape bias is an attentional preference children show for the shape of an
      object over other aspects of the object in a word-learning context. This bias,
      which aids in establishing a word-object pairing, was investigated in 12-, 18-,
      and 24-month-old children (n = 90) across noun, adjective, and no-label
      conditions. The present research presents evidence of development across this
      time span; there was a transition from a label reducing the chance of shape
      extensions to indiscriminate shape extensions to a label increasing the chance of
      shape extensions. This research supports the notion that children are focusing
      their extensions more toward shape during the course of development thereby
      developing a more mature and more specialized shape bias. 

PMID- 25775082
TI  - Long-term functionality of rural water services in developing countries: a system
      dynamics approach to understanding the dynamic interaction of factors.
AB  - Research has shown that sustainability of rural water infrastructure in
      developing countries is largely affected by the dynamic and systemic interactions
      of technical, social, financial, institutional, and environmental factors that
      can lead to premature water system failure. This research employs system dynamics
      modeling, which uses feedback mechanisms to understand how these factors interact
      dynamically to influence long-term rural water system functionality. To do this,
      the research first identified and aggregated key factors from the literature,
      then asked water sector experts to indicate the polarity and strength between
      factors through Delphi and cross impact survey questionnaires, and finally used
      system dynamics modeling to identify and prioritize feedback mechanisms. The
      resulting model identified 101 feedback mechanisms that were dominated primarily
      by three- and four-factor mechanisms that contained some combination of the
      factors: Water System Functionality, Community, Financial, Government,
      Management, and Technology, implying these factors were the most influential on
      long-term functionality. These feedback mechanisms were then scored and
      prioritized, with the most dominant feedback mechanism identified as Water System
      Functionality-Community-Finance-Management. This study showcases a way for
      practitioners to better understand the complexities inherent in rural water
      development using expert opinion and indicates the need for future research in
      rural water service sustainability that investigates the dynamic interaction of
      factors in different contexts. 

PMID- 25775085
TI  - Addressing psychological concerns to practice whole-person health care.

PMID- 25775087
TI  - Everolimus-eluting stents or bypass surgery for multivessel coronary disease.
AB  - BACKGROUND: Results of trials and registry studies have shown lower long-term
      mortality after coronary-artery bypass grafting (CABG) than after percutaneous
      coronary intervention (PCI) among patients with multivessel disease. These
      previous analyses did not evaluate PCI with second-generation drug-eluting
      stents. METHODS: In an observational registry study, we compared the outcomes in
      patients with multivessel disease who underwent CABG with the outcomes in those
      who underwent PCI with the use of everolimus-eluting stents. The primary outcome
      was all-cause mortality. Secondary outcomes were the rates of myocardial
      infarction, stroke, and repeat revascularization. Propensity-score matching was
      used to assemble a cohort of patients with similar baseline characteristics.
      RESULTS: Among 34,819 eligible patients, 9223 patients who underwent PCI with
      everolimus-eluting stents and 9223 who underwent CABG had similar propensity
      scores and were included in the analyses. At a mean follow-up of 2.9 years, PCI
      with everolimus-eluting stents, as compared with CABG, was associated with a
      similar risk of death (3.1% per year and 2.9% per year, respectively; hazard
      ratio, 1.04; 95% confidence interval [CI], 0.93 to 1.17; P=0.50), higher risks of
      myocardial infarction (1.9% per year vs. 1.1% per year; hazard ratio, 1.51; 95%
      CI, 1.29 to 1.77; P<0.001) and repeat revascularization (7.2% per year vs. 3.1%
      per year; hazard ratio, 2.35; 95% CI, 2.14 to 2.58; P<0.001), and a lower risk of
      stroke (0.7% per year vs. 1.0% per year; hazard ratio, 0.62; 95% CI, 0.50 to
      0.76; P<0.001). The higher risk of myocardial infarction with PCI than with CABG
      was not significant among patients with complete revascularization but was
      significant among those with incomplete revascularization (P=0.02 for
      interaction). CONCLUSIONS: In a contemporary clinical-practice registry study,
      the risk of death associated with PCI with everolimus-eluting stents was similar
      to that associated with CABG. PCI was associated with a higher risk of myocardial
      infarction (among patients with incomplete revascularization) and repeat
      revascularization but a lower risk of stroke. (Funded by Abbott Vascular.).

PMID- 25775088
TI  - Dance Class Structure Affects Youth Physical Activity and Sedentary Behavior: A
      Study of Seven Dance Types.
AB  - PURPOSE: The study aims were to determine: (a) how class structure varies by
      dance type, (b) how moderate-to-vigorous physical activity (MVPA) and sedentary
      behavior vary by dance class segments, and (c) how class structure relates to
      total MVPA in dance classes. METHOD: Participants were 291 boys and girls ages 5
      to 18 years old enrolled in 58 dance classes at 21 dance studios in Southern
      California. MVPA and sedentary behavior were assessed with accelerometry, with
      data aggregated to 15-s epochs. Percent and minutes of MVPA and sedentary
      behavior during dance class segments and percent of class time and minutes spent
      in each segment were calculated using Freedson age-specific cut points.
      Differences in MVPA (Freedson 3 Metabolic Equivalents of Tasks age-specific cut
      points) and sedentary behavior ( < 100 counts/min) were examined using mixed
      effects linear regression. RESULTS: The length of each class segment was fairly
      consistent across dance types, with the exception that in ballet, more time was
      spent in technique as compared with private jazz/hip-hop classes and Latin
      flamenco and less time was spent in routine/practice as compared with Latin
      salsa/ballet folklorico. Segment type accounted for 17% of the variance in the
      proportion of the segment spent in MVPA. The proportion of the segment in MVPA
      was higher for routine/practice (44.2%) than for technique (34.7%). The
      proportion of the segment in sedentary behavior was lowest for routine/practice
      (22.8%). CONCLUSION: The structure of dance lessons can impact youths' physical
      activity. Working with instructors to increase time in routine/practice during
      dance classes could contribute to physical activity promotion in youth.

PMID- 25775089
TI  - Visualization by high resolution immunoelectron microscopy of the transient
      receptor potential vanilloid-1 at inhibitory synapses of the mouse dentate gyrus.
AB  - We have recently shown that the transient receptor potential vanilloid type 1
      (TRPV1), a non-selective cation channel in the peripheral and central nervous
      system, is localized at postsynaptic sites of the excitatory perforant path
      synapses in the hippocampal dentate molecular layer (ML). In the present work, we
      have studied the distribution of TRPV1 at inhibitory synapses in the ML. With
      this aim, a preembedding immunogold method for high resolution electron
      microscopy was applied to mouse hippocampus. About 30% of the inhibitory synapses
      in the ML are TRPV1 immunopositive, which is mostly localized perisynaptically
      (~60% of total immunoparticles) at postsynaptic dendritic membranes receiving
      symmetric synapses in the inner 1/3 of the layer. This TRPV1 pattern distribution
      is not observed in the ML of TRPV1 knock-out mice. These findings extend the
      knowledge of the subcellular localization of TRPV1 to inhibitory synapses of the
      dentate molecular layer where the channel, in addition to excitatory synapses, is
      present. 

PMID- 25775090
TI  - Computational prediction and analysis of envelop glycoprotein epitopes of DENV-2
      and DENV-3 Pakistani isolates: a first step towards Dengue vaccine development.
AB  - Dengue fever of tropics is a mosquito transmitted devastating disease caused by
      dengue virus (DENV). There is no effective vaccine available, so far, against any
      of its four serotypes (DENV-1, DENV-2, DENV-3, and DENV-4). There is a need for
      the development of preventive and therapeutic vaccines against DENV to decrease
      the prevalence of dengue fever, especially in Pakistan. In this research, linear
      and conformational B-cell epitopes of envelope glycoprotein of DENV-2 and DENV-3
      (the most prevalent serotypes in Pakistan) were predicted. We used Kolaskar and
      Tongaonkar method for linear epitope prediction, Emini's method for surface
      accessibility prediction and Karplus and Schulz's algorithm for flexibility
      determination. To propose three dimensional epitopes, the E proteins for both
      serotypes were homology modeled by using Phyre2 V 2.0 server, and ElliPro was
      used for the prediction of surface epitopes on their globular structure. Total 21
      and 19 linear epitopes were predicted for DENV-2 and DENV-3 Pakistani isolates
      respectively. Whereas, 5 and 4 discontinuous epitopes were proposed for DENV-2
      and DENV-3 Pakistani isolates respectively. Moreover, the values of surface
      accessibility, flexibility and solvent-accessibility can be helpful in analyzing
      vaccines against DENV-2 and DENV-3. In conclusion, the proposed continuous and
      discontinuous antigenic peptides can be valuable candidates for diagnostic and
      therapeutics of DENV. 

PMID- 25775091
TI  - Analysis of the enamel hypoplasia using micro-CT scanner versus classical method.
AB  - This article demonstrates the use of micro-CT scanning of the teeth surface for
      recognizing and evaluating severity of the enamel hypoplasia. To test
      capabilities of the microtomography versus classical method of evaluation
      hypoplastic defects of the enamel we selected two human teeth (C, M(2)) showing
      different types of enamel hypoplasia: linear, pits, and groove. Examined samples
      derive from archeological material dated on XVII-XVIII AD and excavated in
      Poland. In the current study we proved that micro-CT scanning is a powerful
      technique not only for imaging all kinds of the enamel hypoplasia but also allows
      to perform accurate measurements of the enamel defects. We figure out that
      contrary to the classical method of scoring enamel defects, the micro-computed
      tomography yields adequate data which serve for estimating the length of stress
      episode and length of interval between them. 

PMID- 25775092
TI  - Nab3 facilitates the function of the TRAMP complex in RNA processing via
      recruitment of Rrp6 independent of Nrd1.
AB  - Non-coding RNAs (ncRNAs) play critical roles in gene regulation. In eukaryotic
      cells, ncRNAs are processed and/or degraded by the nuclear exosome, a
      ribonuclease complex containing catalytic subunits Dis3 and Rrp6. The TRAMP
      (Trf4/5-Air1/2-Mtr4 polyadenylation) complex is a critical exosome cofactor in
      budding yeast that stimulates the exosome to process/degrade ncRNAs and human
      TRAMP components have recently been identified. Importantly, mutations in exosome
      and exosome cofactor genes cause neurodegenerative disease. How the TRAMP complex
      interacts with other exosome cofactors to orchestrate regulation of the exosome
      is an open question. To identify novel interactions of the TRAMP exosome
      cofactor, we performed a high copy suppressor screen of a thermosensitive air1/2
      TRAMP mutant. Here, we report that the Nab3 RNA-binding protein of the Nrd1-Nab3
      Sen1 (NNS) complex is a potent suppressor of TRAMP mutants. Unlike Nab3, Nrd1 and
      Sen1 do not suppress TRAMP mutants and Nrd1 binding is not required for Nab3
      mediated suppression of TRAMP suggesting an independent role for Nab3.
      Critically, Nab3 decreases ncRNA levels in TRAMP mutants, Nab3-mediated
      suppression of air1/2 cells requires the nuclear exosome component, Rrp6, and
      Nab3 directly binds Rrp6. We extend this analysis to identify a human RNA binding
      protein, RALY, which shares identity with Nab3 and can suppress TRAMP mutants.
      These results suggest that Nab3 facilitates TRAMP function by recruiting Rrp6 to
      ncRNAs for processing/degradation independent of Nrd1. The data raise the
      intriguing possibility that Nab3 and Nrd1 can function independently to recruit
      Rrp6 to ncRNA targets, providing combinatorial flexibility in RNA processing. 

PMID- 25775093
TI  - Double NF1 inactivation affects adrenocortical function in NF1Prx1 mice and a
      human patient.
AB  - BACKGROUND: Neurofibromatosis type I (NF1, MIM#162200) is a relatively frequent
      genetic condition, which predisposes to tumor formation. Apart from tumors,
      individuals with NF1 often exhibit endocrine abnormalities such as precocious
      puberty (2,5-5% of NF1 patients) and some cases of hypertension (16% of NF1
      patients). Several cases of adrenal cortex adenomas have been described in NF1
      individuals supporting the notion that neurofibromin might play a role in adrenal
      cortex homeostasis. However, no experimental data were available to prove this
      hypothesis. MATERIALS AND METHODS: We analysed Nf1Prx1 mice and one case of
      adrenal cortical hyperplasia in a NF1patient. RESULTS: In Nf1Prx1 mice Nf1 is
      inactivated in the developing limbs, head mesenchyme as well as in the adrenal
      gland cortex, but not the adrenal medulla or brain. We show that adrenal gland
      size is increased in NF1Prx1 mice. Nf1Prx1 female mice showed corticosterone and
      aldosterone overproduction. Molecular analysis of Nf1 deficient adrenals revealed
      deregulation of multiple proteins, including steroidogenic acute regulatory
      protein (StAR), a vital mitochondrial factor promoting transfer of cholesterol
      into steroid making mitochondria. This was associated with a marked upregulation
      of MAPK pathway and a female specific increase of cAMP concentration in murine
      adrenal lysates. Complementarily, we characterized a patient with
      neurofibromatosis type I with macronodular adrenal hyperplasia with ACTH
      independent cortisol overproduction. Comparison of normal control tissue- and
      adrenal hyperplasia- derived genomic DNA revealed loss of heterozygosity (LOH) of
      the wild type NF1 allele, showing that biallelic NF1 gene inactivation occurred
      in the hyperplastic adrenal gland. CONCLUSIONS: Our data suggest that biallelic
      loss of Nf1 induces autonomous adrenal hyper-activity. We conclude that Nf1 is
      involved in the regulation of adrenal cortex function in mice and humans.

PMID- 25775094
TI  - Recent advances in novel heterocyclic scaffolds for the treatment of drug
      resistant malaria.
AB  - Malaria is a major public health problem all over the world, particularly in
      tropical and subtropical countries due to the development of resistance and most
      deadly infection is caused by Plasmodium falciparum. There is a direct need for
      the discovery of new drugs with unique structures and mechanism of action to
      treat sensitive and drug-resistant strains of various plasmodia for radical cure
      of this disease. Traditional compounds such as quinine and related derivatives
      represent a major source for the development of new drugs. This review presents
      recent modifications of 4-aminoquinoline and 8-aminoquinolone rings as leads to
      novel active molecules which are under clinical trials. The review also
      encompasses the other heterocyclic compounds emerged as potential antimalarial
      agents with promising results such as acridinediones and acridinone analogues,
      pyridines and quinolones as antimalarials. Miscellaneous heterocyclics such as
      tetroxane derivatives, indole derivatives, imidazolopiperazine derivatives,
      biscationic choline-based compounds and polymer-linked combined antimalarial
      drugs are also discussed. At last brief introduction to heterocyclics in natural
      products is also reviewed. Most of them have been under clinical trials and found
      to be promising in the treatment of drug-resistant strains of Plasmodium and
      others can be explored for the same purpose. 

PMID- 25775096
TI  - Affinity states of biocides determine bioavailability and release rates in marine
      paints.
AB  - A challenge for the next generation marine antifouling (AF) paints is to deliver
      minimum amounts of biocides to the environment. The candidate AF compound
      medetomidine is here shown to be released at very low concentrations, ie ng ml(
      1) day(-1). Moreover, the release rate of medetomidine differs substantially
      depending on the formulation of the paint, while inhibition of barnacle
      settlement is independent of release to the ambient water, ie the paint with the
      lowest release rate was the most effective in impeding barnacle colonisation.
      This highlights the critical role of chemical interactions between biocide, paint
      carrier and the solid/aqueous interface for release rate and AF performance. The
      results are discussed in the light of differential affinity states of the
      biocide, predicting AF activity in terms of a high surface affinity and preserved
      bioavailability. This may offer a general framework for the design of low-release
      paint systems using biocides for protection against biofouling on marine
      surfaces.

PMID- 25775095
TI  - Esterase activity of carbonic anhydrases serves as surrogate for selecting
      antibodies blocking hydratase activity.
AB  - Carbonic anhydrase 9 (CA9) and carbonic anhydrase 12 (CA12) were proposed as
      potential targets for cancer therapy more than 20 years ago. However, to date,
      there are only very few antibodies that have been described to specifically
      target CA9 and CA12 and also block the enzymatic activity of their targets. One
      of the early stage bottlenecks in identifying CA9- and CA12-inhibiting antibodies
      has been the lack of a high-throughput screening system that would allow for
      rapid assessment of inhibition of the targeted carbon dioxide hydratase activity
      of carbonic anhydrases. In this study, we show that measuring the esterase
      activity of carbonic anhydrase offers a robust and inexpensive screening method
      for identifying antibody candidates that block both hydratase and esterase
      activities of carbonic anhydrase's. To our knowledge, this is the first
      implementation of a facile surrogate-screening assay to identify potential
      therapeutic antibodies that block the clinically relevant hydratase activity of
      carbonic anhydrases. 

PMID- 25775098
TI  - On Compassion.

PMID- 25775097
TI  - Liver regeneration and energetic changes in rats following hepatic radiation
      therapy and hepatocyte transplantation by 31P MRSI.
AB  - BACKGROUND & AIMS: Radiation-induced liver damage (RILD) is a poorly understood
      and potentially devastating complication of hepatic radiation therapy (RT) for
      liver cancers. Previous work has demonstrated that hepatocyte transplantation
      (HT) can ameliorate RILD in rats. We hypothesized that RT inhibits generation of
      cellular ATP and suppresses hepatic regeneration. METHODS: To study the metabolic
      changes that occur in RILD with and without HT, (31)P MRSI data were acquired in
      rats treated with partial hepatectomy (PH) alone, PH with hepatic irradiation
      (PHRT) or PHRT with HT (PHRT+HT). RESULTS: Both [gamma -ATP] and ATP/Pi (31)P
      MRSI signal ratio initially decreased and subsequently returned to baseline
      levels within 2 weeks after PH, which is consistent with other published data.
      Persistently reduced [gamma-ATP] and ATP/Pi (31)P MRSI signal ratio were observed
      in rats up to 20 weeks after PHRT. However, progressive increases in [gamma -ATP]
      were observed over time in the group of rats receiving PHRT+HT. Normal [gamma 
      ATP] was observed 20 weeks after PHRT+HT (vs. PH alone), although, ATP/Pi levels
      did not return to normal after PHRT +HT. Ex vivo histological studies were
      performed to confirm liver repopulation with transplanted hepatocytes and the
      amelioration of pathologic changes of RILD. CONCLUSIONS: These findings suggest
      that (31)P MRSI can be used to monitor the progress of RILD and its amelioration
      using transplanted hepatocytes to simultaneously restore metabolic function while
      replacing host hepatocytes damaged by RT.

PMID- 25775099
TI  - Cost-Effectiveness of Injectable Extended-Release Naltrexone Compared With
      Methadone Maintenance and Buprenorphine Maintenance Treatment for Opioid
      Dependence.
AB  - BACKGROUND: The aim of this study was to estimate the cost-effectiveness of
      injectable extended-release naltrexone (XR-NTX) compared with methadone
      maintenance and buprenorphine maintenance treatment (MMT and BMT, respectively)
      for adult males enrolled in treatment for opioid dependence in the United States
      from the perspective of state-level addiction treatment payers. METHODS: A Markov
      model with daily time cycles was used to estimate the incremental cost per opioid
      free day in a simulated cohort of adult males aged 18-65 over a 6-month period
      from the state health program perspective. RESULTS: XR-NTX is predicted to be
      more effective and more costly than methadone or buprenorphine in our target
      population, with an incremental cost per opioid-free day gained relative to the
      next-most effective treatment (MMT) of $72. The cost-effectiveness of XR-NTX
      relative to MMT was driven by its effectiveness in deterring opioid use while
      receiving treatment. CONCLUSIONS: XR-NTX is a cost-effective medication for
      treating opioid dependence if state addiction treatment payers are willing to pay
      at least $72 per opioid-free day.

PMID- 25775100
TI  - Differences in Adherence to Common Inhaled Medications in COPD.
AB  - OBJECTIVE: To study differences in adherence to common inhaled medications in
      COPD. METHODS: Adherence of 795 patients was recorded from pharmacy records over
      3 years in the COMIC cohort. It was expressed as percentage and deemed good at
      >=75-<=125%, sub-optimal >=50-<75%, and poor <50% (underuse) or >125% (overuse).
      Most patients used more than one medication, so we present 1379 medication
      periods. RESULTS: The percentages of patients with good therapy adherence ranged
      from 43.2 (beclomethasone) -75.8% (tiotropium); suboptimal from 2.3 (budesonide) 
      23.3% (fluticasone); underuse from 4.4 (formoterol/budesonide) -18.2%
      (beclomethasone); and overuse from 5.1 (salmeterol) -38.6% (budesonide). Patients
      using fluticasone or salmeterol/fluticasone have a 2.3 and 2.0-fold increased
      risk of suboptimal versus good adherence compared to tiotropium. Patients using
      salmeterol/fluticasone or beclomethasone have a 2.3- and 4.6-fold increased risk
      of underuse versus good adherence compared to tiotropium. Patients using
      budesonide, salmeterol/fluticasone, formoterol/budesonide, ciclesonide and
      beclomethasone have an increased risk of overuse versus good adherence compared
      to tiotropium. Adherence to inhalation medication is inversely related to lung
      function. CONCLUSION: Therapy adherence to inhalation medication for the
      treatment of COPD is in our study related to the medication prescribed.
      Tiotropium showed the highest percentage of patients with good adherence,
      followed by ciclesonide, both dosed once daily. The idea of improving adherence
      by using combined preparations cannot be confirmed in this study. Further
      research is needed to investigate the possibilities of improving adherence by
      changing inhalation medication.

PMID- 25775101
TI  - Characterization of Stripe Rust Resistance in Wheat Lines with Resistance Gene
      Yr17 and Implications for Evaluating Resistance and Virulence.
AB  - Stripe rust, caused by Puccinia striiformis f. sp. tritici, has been the most
      important foliar wheat disease in south central United States since 2000 when a
      new strain of the pathogen emerged. The resistance gene Yr17 was used by many
      breeding programs to develop resistant cultivars. Although Yr17 was classified as
      a seedling (all-stage) resistance gene conferring a low infection type, seedlings
      with Yr17 frequently had intermediate to high infection types when inoculated
      with isolates that caused little or no disease on adult plants of the same wheat
      lines. The objectives of this study were to determine how to best evaluate Yr17
      resistance in wheat lines and to determine which factors made seedling tests
      involving Yr17 so variable. Stripe rust reactions on wheat seedlings with Yr17
      were influenced by temperature, wheat genotype, pathogen isolate, and the leaf
      (first or second) used to assess the seedling reaction. The most critical factors
      for accurately evaluating Yr17 reactions at the seedling stage were to avoid
      night temperatures below 12 degrees C, to use the first leaf to assess the
      seedling reaction, to use multiple differentials with Yr17 and known avirulent,
      partially virulent and virulent isolates as controls, and to recognize that
      intermediate infection types likely represent a level of partial virulence in the
      pathogen that is insufficient to cause disease on adult plants in the field. 

PMID- 25775102
TI  - From Select Agent to an Established Pathogen: The Response to Phakopsora
      pachyrhizi (Soybean Rust) in North America.
AB  - The pathogen causing soybean rust, Phakopsora pachyrhizi, was first described in
      Japan in 1902. The disease was important in the Eastern Hemisphere for many
      decades before the fungus was reported in Hawaii in 1994, which was followed by
      reports from countries in Africa and South America. In 2004, P. pachyrhizi was
      confirmed in Louisiana, making it the first report in the continental United
      States. Based on yield losses from countries in Asia, Africa, and South America,
      it was clear that this pathogen could have a major economic impact on the yield
      of 30 million ha of soybean in the United States. The response by agencies within
      the United States Department of Agriculture, industry, soybean check-off boards,
      and universities was immediate and complex. The impacts of some of these
      activities are detailed in this review. The net result has been that the once
      dreaded disease, which caused substantial losses in other parts of the world, is
      now better understood and effectively managed in the United States. The disease
      continues to be monitored yearly for changes in spatial and temporal distribution
      so that soybean growers can continue to benefit by knowing where soybean rust is
      occurring during the growing season. 

PMID- 25775103
TI  - Development and Validation of LNA-Based Quantitative Real-Time PCR Assays for
      Detection and Identification of the Root-Knot Nematode Meloidogyne enterolobii in
      Complex DNA Backgrounds.
AB  - Meloidogyne enterolobii is a quarantine root-knot nematode posing a major threat
      to agricultural production systems worldwide. It attacks many host plants,
      including important agricultural crops, ornamentals, and trees. M. enterolobii is
      a highly virulent and pathogenic root-knot nematode species, able to reproduce on
      plants resistant to other Meloidogyne spp. Significant crop damage has been
      reported in Asia, South America, Africa, the United States, France, and
      greenhouses in Switzerland. To identify potential introduction pathways and
      ensure appropriate phytosanitary measures and management strategies, accurate
      detection and identification tools are needed. Therefore, two real-time
      quantitative polymerase chain reaction (PCR) assays based on the second
      intergenic spacer region of the ribosomal DNA cistron and the cytochrome oxidase
      c subunit I (COI) gene using locked nucleic acid probes were developed and
      validated for fast and reliable detection and identification of M. enterolobii.
      Analytical specificity was confirmed with 16 M. enterolobii populations, 16
      populations of eight closely related Meloidogyne spp., and four species from
      other nematode genera. Optimizing and testing the assays on two real-time PCR
      platforms revealed an analytical sensitivity of one juvenile in a background of
      1,000 nematodes and the intended limit of detection of one juvenile per 100 ml of
      soil. Both assays performed equally well, with the COI-based assay showing a
      slightly better performance concerning detection of M. enterolobii target DNA in
      complex DNA backgrounds. 

PMID- 25775104
TI  - Potato Tuber Blight Resistance Phenotypes Correlate with RB Transgene Transcript
      Levels in an Age-Dependent Manner.
AB  - Plants have evolved strategies and mechanisms to detect and respond to pathogen
      attack. Different organs of the same plant may be subjected to different
      environments (e.g., aboveground versus belowground) and pathogens with different
      lifestyles. Accordingly, plants commonly need to tailor defense strategies in an
      organ-specific manner. Phytophthora infestans, causal agent of potato late blight
      disease, infects both aboveground foliage and belowground tubers. We examined the
      efficacy of transgene RB (known for conferring foliar late blight resistance) in
      defending against tuber late blight disease. Our results indicate that the
      presence of the transgene has a positive yet only marginally significant effect
      on tuber disease resistance on average. However, a significant association
      between transgene transcript levels and tuber resistance was established for
      specific transformed lines in an age-dependent manner, with higher transcript
      levels indicating enhanced tuber resistance. Thus, RB has potential to function
      in both foliage and tuber to impart late blight resistance. Our data suggest that
      organ-specific resistance might result directly from transcriptional regulation
      of the resistance gene itself. 

PMID- 25775105
TI  - Detection of a New Luteovirus in Imported Nectarine Trees: A Case Study to
      Propose Adoption of Metagenomics in Post-Entry Quarantine.
AB  - In spring 2013, 5-year-old nectarine (Prunus persica) trees, grafted on peach
      rootstock Nemaguard, were found stunted in a propagation block in California.
      These trees had been propagated from budwood of three nectarine cultivars
      imported from France and cleared through the post-entry quarantine procedure.
      Examination of the canopy failed to reveal any obvious symptoms. However,
      examination of the trunks, after stripping the bark, revealed extensive pitting
      on the woody cylinder. To investigate the etiological agent, double-stranded RNA
      was extracted from bark scrapings from the scion and rootstock portions, and a
      cDNA library was prepared and sequenced using the Illumina platform. BLAST
      analysis of the contigs generated by the de novo assembly of sequence reads
      indicated the presence of a novel luteovirus. Complete sequence of the viral
      genome was determined by sequencing of three overlapping cDNA clones generated by
      reverse transcription-polymerase chain reaction (RT-PCR) and by rapid
      amplification of the 5'- and 3'-termini. The virus genome was comprised of 4,991
      nucleotides with a gene organization similar to members of the genus Luteovirus
      (family Luteoviridae). The presence of the virus, tentatively named Nectarine
      stem pitting-associated virus, was confirmed in symptomatic trees by RT-PCR.
      Discovery of a new virus in nectarine trees after post-entry quarantine indicates
      the importance of including (i) metagenomic analysis by next-generation
      sequencing approach as an essential tool to assess the plant health status, and
      (ii) examination of the woody cylinders as part of the indexing process. 

PMID- 25775106
TI  - Role Bending: Complex Relationships Between Viruses, Hosts, and Vectors Related
      to Citrus Leprosis, an Emerging Disease.
AB  - Citrus leprosis complex is an emerging disease in the Americas, associated with
      two unrelated taxa of viruses distributed in South, Central, and North America.
      The cytoplasmic viruses are Citrus leprosis virus C (CiLV-C), Citrus leprosis
      virus C2 (CiLV-C2), and Hibiscus green spot virus 2, and the nuclear viruses are
      Citrus leprosis virus N (CiLV-N) and Citrus necrotic spot virus. These viruses
      cause local lesion infections in all known hosts, with no natural systemic host
      identified to date. All leprosis viruses were believed to be transmitted by one
      species of mite, Brevipalpus phoenicis. However, mites collected from CiLV-C and
      CiLV-N infected citrus groves in Mexico were identified as B. yothersi and B.
      californicus sensu lato, respectively, and only B. yothersi was detected from
      CiLV-C2 and CiLV-N mixed infections in the Orinoco regions of Colombia.
      Phylogenetic analysis of the helicase, RNA-dependent RNA polymerase 2 domains and
      p24 gene amino acid sequences of cytoplasmic leprosis viruses showed a close
      relationship with recently deposited mosquito-borne negevirus sequences. Here, we
      present evidence that both cytoplasmic and nuclear viruses seem to replicate in
      viruliferous Brevipalpus species. The possible replication in the mite vector and
      the close relationship with mosquito borne negeviruses are consistent with the
      concept that members of the genus Cilevirus and Higrevirus originated in mites
      and citrus may play the role of mite virus vector. 

PMID- 25775107
TI  - Phenotypic and Genotypic Characterization of Race TKTTF of Puccinia graminis f.
      sp. tritici that Caused a Wheat Stem Rust Epidemic in Southern Ethiopia in 2013
      14.
AB  - A severe stem rust epidemic occurred in southern Ethiopia during November 2013 to
      January 2014, with yield losses close to 100% on the most widely grown wheat
      cultivar, 'Digalu'. Sixty-four stem rust samples collected from the regions were
      analyzed. A meteorological model for airborne spore dispersal was used to
      identify which regions were most likely to have been infected from postulated
      sites of initial infection. Based on the analyses of 106 single-pustule isolates
      derived from these samples, four races of Puccinia graminis f. sp. tritici were
      identified: TKTTF, TTKSK, RRTTF, and JRCQC. Race TKTTF was found to be the
      primary cause of the epidemic in the southeastern zones of Bale and Arsi.
      Isolates of race TKTTF were first identified in samples collected in early
      October 2013 from West Arsi. It was the sole or predominant race in 31 samples
      collected from Bale and Arsi zones after the stem rust epidemic was established.
      Race TTKSK was recovered from 15 samples from Bale and Arsi zones at low
      frequencies. Genotyping indicated that isolates of race TKTTF belongs to a
      genetic lineage that is different from the Ug99 race group and is composed of two
      distinct genetic types. Results from evaluation of selected germplasm indicated
      that some cultivars and breeding lines resistant to the Ug99 race group are
      susceptible to race TKTTF. Appearance of race TKTTF and the ensuing epidemic
      underlines the continuing threats and challenges posed by stem rust not only in
      East Africa but also to wider-scale wheat production. 

PMID- 25775108
TI  - Neighborhood support network, perceived proximity to community facilities and
      depressive symptoms among low socioeconomic status Chinese elders.
AB  - OBJECTIVES: Depressive symptoms are common in older people; most previous
      research on elderly depression focused on individual-level characteristics or
      neighborhood socioeconomic status. Modifiable neighborhood characteristics of
      older people dwelling in low-income communities are under-studied. This study
      aims to identify potentially modifiable social and physical neighborhood
      characteristics that influence depressive symptoms independent of individual
      level characteristics among older Chinese. METHOD: Data came from a cross
      sectional survey conducted in four low-income public rental housing estates in
      Hong Kong in 2012. We interviewed a total of 400 elderly residents. The
      structured questionnaire covered demographics, activities of daily living, recent
      fall history, neighborhood support networks, and perceived proximity by walk to
      community facilities. Multiple regression was used to test whether inclusion of
      neighborhood factors in addition to individual characteristics increases model
      fit in explaining depressive symptoms in elders with low socioeconomic status.
      RESULTS: At individual level, activities of daily living and income significantly
      predicted depressive symptoms. Receiving support from friends or neighbors is
      associated with fewer depressive symptoms. However, participants who received
      organizational support had a 1.17 points of increase on the 15-item Geriatric
      Depression Scale (GDS-15). At-ease walkable proximity to medical facilities was
      positively associated with a better GDS score. CONCLUSION: Neighborhood support
      networks and perceived proximity by walk to community facilities contribute
      significantly to depressive symptoms among low-income elders. Programs and
      policies that facilitate neighborhood support and commuting or promote facility
      accessibility may help ameliorate depressive symptoms common among low-income
      elders.

PMID- 25775109
TI  - I2-catalyzed synthesis of substituted imidazoles from vinyl azides and
      benzylamines.
AB  - A novel and efficient I2-catalyzed oxidative tandem cyclization of simple vinyl
      azides and benzylamines has been developed for the synthesis of substituted
      imidazoles. In this reaction, various substituted groups on vinyl azides and
      benzylamines proceed smoothly and the desired imidazoles are obtained in moderate
      to good yields. 

PMID- 25775110
TI  - Development of interpersonal coordination between peers during a drumming task.
AB  - During social interaction, the behavior of interacting partners becomes
      coordinated. Although interpersonal coordination is well-studied in adults,
      relatively little is known about its development. In this project we explored how
      2-, 3-, and 4-year-old children spontaneously coordinated their drumming with a
      peer. Results showed that all children adapted their drumming to their partner's
      drumming by starting and stopping their drumming in a coordinated fashion, but
      only 4-year-olds adapted the rhythmic structure of their drumming to their
      partner's drumming. In all age groups, children showed similarly stable drumming.
      Typically, it was 1 of the 2 children who initiated drumming throughout the
      session. The results of this study offer new insights into the development of
      interpersonal coordination abilities in early childhood.

PMID- 25775111
TI  - The latent structure of secure base script knowledge.
AB  - There is increasing evidence that attachment representations abstracted from
      childhood experiences with primary caregivers are organized as a cognitive script
      describing secure base use and support (i.e., the secure base script). To date,
      however, the latent structure of secure base script knowledge has gone unexamined
      this despite that such basic information about the factor structure and
      distributional properties of these individual differences has important
      conceptual implications for our understanding of how representations of early
      experience are organized and generalized, as well as methodological significance
      in relation to maximizing statistical power and precision. In this study, we
      report factor and taxometric analyses that examined the latent structure of
      secure base script knowledge in 2 large samples. Results suggested that variation
      in secure base script knowledge-as measured by both the adolescent (N = 674) and
      adult (N = 714) versions of the Attachment Script Assessment-is generalized
      across relationships and continuously distributed.

PMID- 25775112
TI  - Is education associated with improvements in general cognitive ability, or in
      specific skills?
AB  - Previous research has indicated that education influences cognitive development,
      but it is unclear what, precisely, is being improved. Here, we tested whether
      education is associated with cognitive test score improvements via domain-general
      effects on general cognitive ability (g), or via domain-specific effects on
      particular cognitive skills. We conducted structural equation modeling on data
      from a large (n = 1,091), longitudinal sample, with a measure of intelligence at
      age 11 years and 10 tests covering a diverse range of cognitive abilities taken
      at age 70. Results indicated that the association of education with improved
      cognitive test scores is not mediated by g, but consists of direct effects on
      specific cognitive skills. These results suggest a decoupling of educational
      gains from increases in general intellectual capacity.

PMID- 25775113
TI  - Self-assembling DNA dendrimer for effective delivery of immunostimulatory CpG DNA
      to immune cells.
AB  - DNA dendrimers consisting of several branched DNA units connected to each other
      using DNA ligase were quite effective for the delivery of immunostimulatory CpG
      DNA to immune cells. Therapeutic application of such DNA dendrimers, however, is
      hampered by the use of the ligase. Here, we report that self-assembling DNA
      dendrimers with high immunostimulatory potency can be prepared without DNA
      ligases. Annealing of DNA consisting of DNA units with elongated adhesive ends
      resulted in the formation of DNA dendrimers. Atomic force microscopy revealed
      that the several preparations of DNA dendrimers resulted in dendritic structures
      as designed. The cellular uptake of DNA dendrimers by mouse macrophage-like
      RAW264.7 cells and subsequent release of tumor necrosis factor-alpha were
      dependent on the structural complexity of the dendrimers. These results indicate
      that the ligation-free, self-assembling DNA dendrimers are a potent system for
      the delivery of immunostimulatory CpG DNA to immune cells. 

PMID- 25775114
TI  - Three-state near-infrared electrochromism at the molecular scale.
AB  - Self-assembled monolayer films of a cyclometalated ruthenium complex with a redox
      active amine substituent and three carboxylic acid groups have been prepared on
      ITO electrode surfaces. The obtained thin films show three-state electrochromic
      switching with low electrochemical potential inputs and high near-infrared
      absorbance outputs. Thanks to the long retention time of each oxidation states,
      these films have been used to demonstrate surface-confined flip-flop memory
      functions with high ON/OFF ratios at the molecular scale. 

PMID- 25775115
TI  - Impact of the distance from the stent edge to the residual plaque on edge
      restenosis following everolimus-eluting stent implantation.
AB  - OBJECTIVES: This study aimed to assess the relation between stent edge restenosis
      (SER) and the distance from the stent edge to the residual plaque using
      quantitative intravascular ultrasound. BACKGROUND: Although percutaneous coronary
      intervention with drug-eluting stents has improved SER rates, determining an
      appropriate stent edge landing zone can be challenging in cases of diffuse plaque
      lesions. It is known that edge vascular response can occur within 2 mm from the
      edge of a bare metal stent, but the distance to the adjacent plaque has not been
      evaluated for drug-eluting stents. METHODS: A total of 97 proximal residual
      plaque lesions (plaque burden [PB] >40%) treated with everolimus-eluting stents
      were retrospectively evaluated to determine the distance from the stent edge to
      the residual plaque. RESULTS: The SER group had significantly higher PB (59.1 +/-
      6.1% vs. 51.9 +/- 9.1% for non-SER; P = 0.04). Higher PB was associated with SER,
      with the cutoff value of 54.74% determined using receiver operating
      characteristic (ROC) curve analysis. At this cutoff value of PB, the distance
      from the stent edge to the lesion was significantly associated with SER (odds
      ratio = 2.05, P = 0.035). The corresponding area under the ROC curve was 0.725,
      and the cutoff distance value for predicting SER was 1.0 mm. CONCLUSION: An
      interval less than 1 mm from the proximal stent edge to the nearest point with
      the determined PB cutoff value of 54.74% was significantly associated with SER in
      patients with residual plaque lesions.

PMID- 25775116
TI  - Droplet interfaced parallel and quantitative microfluidic-based separations.
AB  - High-throughput, quantitative, and rapid microfluidic-based separations has been
      a long-sought goal for applications in proteomics, genomics, biomarker discovery,
      and clinical diagnostics. Using droplet-interfaced microchip electrophoresis
      (MCE) techniques, we have developed a novel parallel MCE platform, based on the
      concept of combining the Slipchip principle with a newly developed "Gelchip". The
      platform consists of two plastic plates, with droplet wells on one plate and
      separation channels with preloaded/cured gel in the other. A single relative
      movement of one plate enables generation and then loading of multiple sample
      droplets in parallel into the separation channels, allowing electrophoretic
      separation of biomolecules in the droplets in parallel and with high-throughput.
      As proof of concept, we demonstrated the separation of 30 sub-nL sample droplets
      containing fluorescent dyes or DNA fragments. 

PMID- 25775117
TI  - The epidemiology and geographic distribution of nontuberculous mycobacteria
      clinical isolates from sputum samples in the eastern region of China.
AB  - BACKGROUND: Nontuberculous mycobacteria (NTM) have been reported to be increasing
      worldwide and its geographic distribution differs by region. The aim of this
      study was to describe the epidemiology and distribution of NTM in the eastern
      part of China. METHODS: Sputum samples were collected from 30 surveillance sites
      for tuberculosis drug resistance test from May 1, 2008 to December 31, 2008.
      Identification was performed using a biochemical test, multiplex PCR and GenoType
      Mycobacterium CM/AS assay. RESULTS: A total of 1779 smear positive clinical
      isolates were obtained, of which 60 (3.37%) were NTM. Five species/complex of NTM
      were identified; M. intracellulare was the predominated species (68.33%),
      followed by M. abscessus-M. immunogenum (13.33%), Mycobacterium spec. (10.00%),
      M. Kansasii (6.67%) and M. peregrinum-M. alvei-M. septicum (1.67%). CONCLUSION:
      M. intracellulare was the main species of NTM in the eastern part of China and
      clinical physicians should pay more attention to NTM induced pulmonary disease.

PMID- 25775118
TI  - Surface modification of TiO2 nanocrystals by WO(x) coating or wrapping:
      solvothermal synthesis and enhanced surface chemistry.
AB  - TiO2 anatase nanocrystals were prepared by solvothermal processing of Ti
      chloroalkoxide in oleic acid, in the presence of W chloroalkoxide, with W/Ti
      nominal atomic concentration (R(w)) ranging from 0.16 to 0.64. The as-prepared
      materials were heat-treated up to 500  degrees C for thermal stabilization and
      sensing device processing. For R(0.16), the as-prepared materials were
      constituted by an anatase core surface-modified by WO(x) monolayers. This
      structure persisted up to 500  degrees C, without any WO3 phase segregation. For
      R(w) up to R(0.64), the anatase core was initially wrapped by an amorphous WO(x)
      gel. Upon heat treatment, the WO(x) phase underwent structural reorganization,
      remaining amorphous up to 400  degrees C and forming tiny WO3 nanocrystals
      dispersed into the TiO2 host after heating at 500  degrees C, when part of
      tungsten also migrated into the TiO2 structure, resulting in structural and
      electrical modification of the anatase host. The ethanol sensing properties of
      the various materials were tested and compared with pure TiO2 and WO3 analogously
      prepared. They showed that even the simple surface modification of the TiO2 host
      resulted in a 3 orders of magnitude response improvement with respect to pure
      TiO2.

PMID- 25775119
TI  - Ring-strain-enabled reaction discovery: new heterocycles from
      bicyclo[1.1.0]butanes.
AB  - Mechanistically as well as synthetically, bicyclo[1.1.0]butanes represent one of
      the most fascinating classes of organic compounds. They offer a unique blend of
      compact size (four carbon atoms), high reactivity (strain energy of 66 kcal/mol),
      and mechanistic pathway diversity that can be harvested for the rapid assembly of
      complex scaffolds. The C(1)-C(3) bond combines the electronic features of both
      sigma and pi bonds with facile homolytic and heterolytic bond dissociation
      properties and thereby readily engages pericyclic, transition-metal-mediated,
      nucleophilic, and electrophilic pathways as well as radical acceptor and donor
      substrates. Despite this multifaceted reaction profile and recent advances in the
      preparation of bicylo[1.1.0]butanes, the current portfolio of synthetic
      applications is still limited compared with those of cyclopropanes and
      cyclobutanes. In this Account, we describe our work over the past decade on the
      exploration of substituent effects on the ring strain and the reactivity of
      bicyclo[1.1.0]butanes, particularly in the context of metal-mediated processes.
      We first describe Rh(I)-catalyzed cycloisomerization reactions of N-allyl amines
      to give pyrrolidine and azepine heterocycles. The regioselectivity of the C,C
      bond insertion/ring-opening step in these reactions is controlled by the
      phosphine ligand. After metal carbene formation, an intramolecular
      cyclopropanation adds a second fused ring system. A proposed mechanism
      rationalizes why rhodium(I) complexes with monodentate ligands favor five
      membered heterocycles, as opposed to Rh(I)-bidentate ligand catalysts, which
      rearrange N-allyl amines to seven-membered heterocycles. The scope of Rh(I)
      catalyzed cycloisomerization reactions was extended to allyl ethers, which
      provide a mixture of five- and seven-membered cyclic ethers regardless of the
      nature of the phosphine additive and Rh(I) precatalyst. The chemical diversity of
      these cycloisomerization products was further expanded by a consecutive one-pot
      metathesis reaction. Rh(I)-catalyzed cycloisomerizations of propargyl amides,
      ethers, and electron-deficient bicyclo[1.1.0]butanes diverged mechanistically and
      often led to a significant number of decomposition products. In these cases,
      Pt(II) emerged as a superior, more alkynophilic late transition metal with its
      own mechanistic peculiarities. While monosubstituted bicyclo[1.1.0]butanes led to
      the formation of tetrahydropyridines, 1,3-disubstituted and electron-deficient
      bicyclo[1.1.0]butanes reacted distinctly differently with Pt(II) and ultimately
      provided a complementary set of nitrogen- and oxygen-containing cyclic scaffolds.
      The metal-catalyzed ring transformations of bicyclo[1.1.0]butanes presented
      herein suggest additional strategies for new reaction discoveries that can access
      a wide variety of novel cyclic frameworks from relatively simple starting
      materials. In addition, these case studies highlight the considerable potential
      for future applications in natural products, medicinal, and diversity-oriented
      synthesis based on the wealth of mechanistic pathways available to these strained
      small-ring carbocycles. 

PMID- 25775121
TI  - Correction: Incomplete radiofrequency ablation enhances invasiveness and
      metastasis of residual cancer of hepatocellular carcinoma cell HCCLM3 via
      activating beta-catenin signaling.

PMID- 25775120
TI  - Atrial fibrillation complicated by heart failure induces distinct remodeling of
      calcium cycling proteins.
AB  - Atrial fibrillation (AF) and heart failure (HF) are two of the most common
      cardiovascular diseases. They often coexist and account for significant morbidity
      and mortality. Alterations in cellular Ca2+ homeostasis play a critical role in
      AF initiation and maintenance. This study was designed to specifically elucidate
      AF-associated remodeling of atrial Ca2+ cycling in the presence of mild HF. AF
      was induced in domestic pigs by atrial burst pacing. The animals underwent
      electrophysiologic and echocardiographic examinations. Ca2+ handling proteins
      were analyzed in right atrial tissue obtained from pigs with AF (day 7; n = 5)
      and compared to sinus rhythm (SR) controls (n = 5). During AF, animals exhibited
      reduction of left ventricular ejection fraction (from 73% to 58%) and prolonged
      atrial refractory periods. AF and HF were associated with suppression of protein
      kinase A (PKA)RII (-62%) and Ca2+-calmodulin-dependent kinase II (CaMKII) delta
      by 37%, without changes in CaMKIIdelta autophosphorylation. We further detected
      downregulation of L-type calcium channel (LTCC) subunit alpha2 (-75%),
      sarcoplasmic reticulum Ca2+-ATPase (Serca) 2a (-29%), phosphorylated
      phospholamban (Ser16, -92%; Thr17, -70%), and phospho-ryanodine receptor 2 (RyR2)
      (Ser2808, -62%). Na+-Ca2+ exchanger (NCX) levels were upregulated (+473%),
      whereas expression of Ser2814-phosphorylated RyR2 and LTCCalpha1c subunits was
      not significantly altered. In conclusion, AF produced distinct arrhythmogenic
      remodeling of Ca2+ handling in the presence of tachycardia-induced mild HF that
      is different from AF without structural alterations. The changes may provide a
      starting point for personalized approaches to AF treatment. 

PMID- 25775122
TI  - Peer outreach work as economic activity: implications for HIV prevention
      interventions among female sex workers.
AB  - Female sex workers (FSWs) who work as peer outreach workers in HIV prevention
      programs are drawn from poor socio-economic groups and consider outreach work,
      among other things, as an economic activity. Yet, while successful HIV prevention
      outcomes by such programs are attributed in part to the work of peers who have
      dense relations with FSW communities, there is scant discussion of the economic
      implications for FSWs of their work as peers. Using observational data obtained
      from an HIV prevention intervention for FSWs in south India, we examined the
      economic benefits and costs to peers of doing outreach work and their
      implications for sex workers' economic security. We found that peers considered
      their payment incommensurate with their workload, experienced long delays
      receiving compensation, and at times had to advance money from their pockets to
      do their assigned peer outreach work. For the intervention these conditions
      resulted in peer attrition and difficulties in recruitment of new peer workers.
      We discuss the implications of these findings for uptake of services, and the
      possibility of reaching desired HIV outcomes. Inadequate and irregular
      compensation to peers and inadequate budgetary outlays to perform their community
      based outreach work could weaken peers' relationships with FSW community members,
      undermine the effectiveness of peer-mediated HIV prevention programs and
      invalidate arguments for the use of peers. 

PMID- 25775123
TI  - Biophysical analysis of anopheles gambiae leucine-rich repeat proteins APL1A1,
      APL1B [corrected] and APL1C and their interaction with LRIM1.
AB  - Natural infection of Anopheles gambiae by malaria-causing Plasmodium parasites is
      significantly influenced by the APL1 genetic locus. The locus contains three
      closely related leucine-rich repeat (LRR) genes, APL1A, APL1B and APL1C. Multiple
      studies have reported the participation of APL1A-C in the immune response of A.
      gambiae to invasion by both rodent and human Plasmodium isolates. APL1C forms a
      heterodimer with the related LRR protein LRIM1 via a C-terminal coiled-coil
      domain that is also present in APL1A and APL1B. The LRIM1/APL1C heterodimer
      protects A. gambiae from infection by binding the complement-like protein TEP1 to
      form a stable and active immune complex. Here we report solution x-ray scatting
      data for the LRIM1/APL1C heterodimer, the oligomeric state of LRIM1/APL1 LRR
      domains in solution and the crystal structure of the APL1B LRR domain. The
      LRIM1/APL1C heterodimeric complex has a flexible and extended structure in
      solution. In contrast to the APL1A, APL1C and LRIM1 LRR domains, the APL1B LRR
      domain is a homodimer. The crystal structure of APL1B-LRR shows that the
      homodimer is formed by an N-terminal helix that complements for the absence of an
      N-terminal capping motif in APL1B, which is a unique distinction within the
      LRIM1/APL1 protein family. Full-length APL1A1 and APL1B form a stable complex
      with LRIM1. These results support a model in which APL1A1, APL1B and APL1C can
      all form an extended, flexible heterodimer with LRIM1, providing a repertoire of
      functional innate immune complexes to protect A. gambiae from a diverse array of
      pathogens. 

PMID- 25775125
TI  - Evidence base of clinical studies on Tai Chi: a bibliometric analysis.
AB  - BACKGROUND: The safety and health benefits of Tai Chi mind-body exercise has been
      documented in a large number of clinical studies focused on specific diseases and
      health conditions. The objective of this systematic review is to more
      comprehensively summarize the evidence base of clinical studies of Tai Chi for
      healthcare. METHODS AND FINDINGS: We searched for all types of clinical studies
      on Tai chi in PubMed, the Cochrane Library and four major Chinese electronic
      databases from their inception to July 2013. Data were analyzed using SPSS17.0
      software. A total of 507 studies published between 1958 and 2013 were identified,
      including 43 (8.3%) systematic reviews of clinical studies, 255 (50.3%)
      randomized clinical trials, 90 (17.8%) non-randomized controlled clinical
      studies, 115 (22.7%) case series and 4 (0.8%) case reports. The top 10
      diseases/conditions was hypertension, diabetes, osteoarthritis, osteoporosis or
      osteopenia, breast cancer, heart failure, chronic obstructive pulmonary disease,
      coronary heart disease, schizophrenia, and depression. Many healthy participants
      practiced Tai Chi for the purpose of health promotion or preservation. Yang style
      Tai Chi was the most popular, and Tai Chi was frequently practiced two to three 1
      hour sessions per week for 12 weeks. Tai Chi was used alone in more than half of
      the studies (58.6%), while in other studies Tai Chi was applied in combination
      with other therapies including medications, health education and other physical
      therapies. The majority of studies (94.1%) reported positive effects of Tai Chi,
      5.1% studies reported uncertain effects and 0.8% studies reported negative
      effects. No serious adverse events related to Tai Chi were reported. CONCLUSIONS:
      The quantity and evidence base of clinical studies on Tai Chi is substantial.
      However, there is a wide variation in Tai Chi intervention studied and the
      reporting of Tai Chi intervention needs to be improved. Further well-designed and
      reported studies are recommended to confirm the effects of Tai Chi for the
      frequently reported diseases/conditions.

PMID- 25775124
TI  - IL-24 inhibits lung cancer cell migration and invasion by disrupting the SDF
      1/CXCR4 signaling axis.
AB  - BACKGROUND: The stromal cell derived factor (SDF)-1/chemokine receptor (CXCR)-4
      signaling pathway plays a key role in lung cancer metastasis and is molecular
      target for therapy. In the present study we investigated whether interleukin (IL)
      24 can inhibit the SDF-1/CXCR4 axis and suppress lung cancer cell migration and
      invasion in vitro. Further, the efficacy of IL-24 in combination with CXCR4
      antagonists was investigated. METHODS: Human H1299, A549, H460 and HCC827 lung
      cancer cell lines were used in the present study. The H1299 lung cancer cell line
      was stably transfected with doxycycline-inducible plasmid expression vector
      carrying the human IL-24 cDNA and used in the present study to determine the
      inhibitory effects of IL-24 on SDF-1/CXCR4 axis. H1299 and A549 cell lines were
      used in transient transfection studies. The inhibitory effects of IL-24 on
      SDF1/CXCR4 and its downstream targets were analyzed by quantitative RT-PCR,
      western blot, luciferase reporter assay, flow cytometry and immunocytochemistry.
      Functional studies included cell migration and invasion assays. PRINCIPAL
      FINDINGS: Endogenous CXCR4 protein expression levels varied among the four human
      lung cancer cell lines. Doxycycline-induced IL-24 expression in the H1299-IL24
      cell line resulted in reduced CXCR4 mRNA and protein expression. IL-24 post
      transcriptionally regulated CXCR4 mRNA expression by decreasing the half-life of
      CXCR4 mRNA (>40%). Functional studies showed IL-24 inhibited tumor cell migration
      and invasion concomitant with reduction in CXCR4 and its downstream targets
      (pAKTS473, pmTORS2448, pPRAS40T246 and HIF-1alpha). Additionally, IL-24 inhibited
      tumor cell migration both in the presence and absence of the CXCR4 agonist, SDF
      1. Finally, IL-24 when combined with CXCR4 inhibitors (AMD3100, SJA5) or with
      CXCR4 siRNA demonstrated enhanced inhibitory activity on tumor cell migration.
      CONCLUSIONS: IL-24 disrupts the SDF-1/CXCR4 signaling pathway and inhibits lung
      tumor cell migration and invasion. Additionally, IL-24, when combined with CXCR4
      inhibitors exhibited enhanced anti-metastatic activity and is an attractive
      therapeutic strategy for lung metastasis.

PMID- 25775126
TI  - Viral infection of human lung macrophages increases PDL1 expression via IFNbeta.
AB  - Lung macrophages are an important defence against respiratory viral infection and
      recent work has demonstrated that influenza-induced macrophage PDL1 expression in
      the murine lung leads to rapid modulation of CD8+ T cell responses via the PD1
      receptor. This PD1/PDL1 pathway may downregulate acute inflammatory responses to
      prevent tissue damage. The aim of this study was to investigate the mechanisms of
      PDL1 regulation by human macrophages in response to viral infection. Ex-vivo
      viral infection models using influenza and RSV were established in human lung
      explants, isolated lung macrophages and monocyte-derived macrophages (MDM) and
      analysed by flow cytometry and RT-PCR. Incubation of lung explants, lung
      macrophages and MDM with X31 resulted in mean cellular infection rates of 18%,
      18% and 29% respectively. Viral infection significantly increased cell surface
      expression of PDL1 on explant macrophages, lung macrophages and MDM but not
      explant epithelial cells. Infected MDM induced IFNgamma release from autologous
      CD8+ T cells, an effect enhanced by PDL1 blockade. We observed increases in PDL1
      mRNA and IFNbeta mRNA and protein release by MDM in response to influenza
      infection. Knockdown of IFNbeta by siRNA, resulted in a 37.5% reduction in
      IFNbeta gene expression in response to infection, and a significant decrease in
      PDL1 mRNA. Furthermore, when MDM were incubated with IFNbeta, this cytokine
      caused increased expression of PDL1 mRNA. These data indicate that human
      macrophage PDL1 expression modulates CD8+ cell IFNgamma release in response to
      virus and that this expression is regulated by autologous IFNbeta production. 

PMID- 25775127
TI  - Dehydrogenative polymerization of coniferyl alcohol in artificial polysaccharides
      matrices: effects of xylan on the polymerization.
AB  - To elucidate the influence of wood polysaccharide components on lignin formation
      in vitro, models for polysaccharide matrix in wood secondary cell wall were
      fabricated from two types of bacterial cellulosic films, flat film (FBC) and
      honeycomb-patterned film (HPBC), as basic frameworks by depositing xylan onto the
      films. An endwise type of dehydrogenative polymerization, "Zutropfverfahren", of
      coniferyl alcohol was attempted in the films with/without xylan. The resultant
      dehydrogenation polymer (DHP) was generated inside and outside xylan-deposited
      films, whereas DHP was deposited only outside the films without xylan. The amount
      of the generated DHP in the xylan-deposited films was larger than that in the
      films without xylan. The frequency of 8-O-4' interunitary linkage in DHP was also
      increased by the xylan deposition. These results suggest that xylan acts as a
      scaffold for DHP deposition in polysaccharides matrix and as a structure
      regulator for the formation of the 8-O-4' linkage. In addition, mechanical
      properties, i.e., tensile strength and modulus of elasticity (MOE), of both
      cellulosic films were found to be augmented by the deposition of xylan and DHP.
      Especially, DHP deposition remarkably enhanced MOE. Such effects of xylan on DHP
      formation and augmentation of mechanical strength were clearly observed for HPBC,
      revealing that HPBC is a promising framework model to investigate wood cell wall
      formation in vitro. 

PMID- 25775128
TI  - Dynamics of Sun5 localization during spermatogenesis in wild type and Dpy19l2
      knock-out mice indicates that Sun5 is not involved in acrosome attachment to the
      nuclear envelope.
AB  - The acrosome is an organelle that is central to sperm physiology and a defective
      acrosome biogenesis leads to globozoospermia, a severe male infertility. The
      identification of the actors involved in acrosome biogenesis is therefore
      particularly important to decipher the molecular pathogeny of globozoospermia. We
      recently showed that a defect in the DPY19L2 gene is present in more than 70% of
      globozoospermic men and demonstrated that Dpy19l2, located in the inner nuclear
      membrane, is the first protein involved in the attachment of the acrosome to the
      nuclear envelope (NE). SUN proteins serve to link the nuclear envelope to the
      cytoskeleton and are therefore good candidates to participate in acrosome-nucleus
      attachment, potentially by interacting with DPY19L2. In order to characterize new
      actors of acrosomal attachment, we focused on Sun5 (also called Spag4l), which is
      highly expressed in male germ cells, and investigated its localization during
      spermatogenesis. Using immunohistochemistry and Western blot experiments in mice,
      we showed that Sun5 transits through different cellular compartments during
      meiosis. In pachytene spermatocytes, it is located in a membranous compartment
      different to the reticulum. In round spermatids, it progresses to the Golgi and
      the NE before to be located to the tail/head junction in epididymal sperm.
      Interestingly, we demonstrate that Sun5 is not, as initially reported, facing the
      acrosome but is in fact excluded from this zone. Moreover, we show that in
      Dpy19l2 KO spermatids, upon the detachment of the acrosome, Sun5 relocalizes to
      the totality of the NE suggesting that the acrosome attachment excludes Sun5 from
      the NE facing the acrosome. Finally, Western-blot experiments demonstrate that
      Sun5 is glycosylated. Overall, our work, associated with other publications,
      strongly suggests that the attachment of the acrosome to the nucleus does not
      likely depend on the formation of SUN complexes. 

PMID- 25775129
TI  - Prenatal parental separation and body weight, including development of overweight
      and obesity later in childhood.
AB  - BACKGROUND: Early parental separation may be a stress factor causing a long-term
      alteration in the hypothalamic-pituitary-adrenal-axis activity possibly impacting
      on the susceptibility to develop overweight and obesity in offspring. We aimed to
      examine the body mass index (BMI) and the risk of overweight and obesity in
      children whose parents lived separately before the child was born. METHODS: A
      follow-up study was conducted using data from the Aarhus Birth Cohort in Denmark
      and included 2876 children with measurements of height and weight at 9-11-years
      of-age, and self-reported information on parental cohabitation status at child
      birth and at 9-11-years-of-age. Quantile regression was used to estimate the
      difference in median BMI between children whose parents lived separately (n =
      124) or together (n = 2752) before the birth. We used multiple logistic
      regression to calculate odds ratio (OR) for overweight and obesity, adjusted for
      gender, parity, breast feeding status, and maternal pre-pregnancy BMI, weight
      gain during pregnancy, age and educational level at child birth; with and without
      possible intermediate factors birth weight and maternal smoking during pregnancy.
      Due to a limited number of obese children, OR for obesity was adjusted for the a
      priori confounder maternal pre-pregnancy BMI only. RESULTS: The difference in
      median BMI was 0.54 kg/m2 (95% confidence intervals (CI): 0.10; 0.98) between
      children whose parents lived separately before birth and children whose parents
      lived together. The risk of overweight and obesity was statistically
      significantly increased in children whose parents lived separately before the
      birth of the child; OR 2.29 (95% CI: 1.18; 4.45) and OR 2.81 (95% CI: 1.05;
      7.51), respectively. Additional, adjustment for possible intermediate factors did
      not substantially change the estimates. CONCLUSION: Parental separation before
      child birth was associated with higher BMI, and increased risk of overweight and
      obesity in 9-11-year-old children; this may suggest a fetal programming effect or
      unmeasured difference in psychosocial factors between separated and non-separated
      parents.

PMID- 25775130
TI  - The complexity of crime network data: a case study of its consequences for crime
      control and the study of networks.
AB  - The field of social network analysis has received increasing attention during the
      past decades and has been used to tackle a variety of research questions, from
      prevention of sexually transmitted diseases to humanitarian relief operations. In
      particular, social network analyses are becoming an important component in
      studies of criminal networks and in criminal intelligence analysis. At the same
      time, intelligence analyses and assessments have become a vital component of
      modern approaches in policing, with policy implications for crime prevention,
      especially in the fight against organized crime. In this study, we have a unique
      opportunity to examine one specific Swedish street gang with three different
      datasets. These datasets are the most common information sources in studies of
      criminal networks: intelligence, surveillance and co-offending data. We use the
      data sources to build networks, and compare them by computing distance,
      centrality, and clustering measures. This study shows the complexity factor by
      which different data sources about the same object of study have a fundamental
      impact on the results. The same individuals have different importance ranking
      depending on the dataset and measure. Consequently, the data source plays a vital
      role in grasping the complexity of the phenomenon under study. Researchers,
      policy makers, and practitioners should therefore pay greater attention to the
      biases affecting the sources of the analysis, and be cautious when drawing
      conclusions based on intelligence assessments and limited network data. This
      study contributes to strengthening social network analysis as a reliable tool for
      understanding and analyzing criminality and criminal networks. 

PMID- 25775131
TI  - Glyceraldehyde 3-phosphate dehydrogenase-telomere association correlates with
      redox status in Trypanosoma cruzi.
AB  - Glyceraldehyde 3-phosphate dehydrogenase (GAPDH) is a classical metabolic enzyme
      involved in energy production and plays a role in additional nuclear functions,
      including transcriptional control, recognition of misincorporated nucleotides in
      DNA and maintenance of telomere structure. Here, we show that the recombinant
      protein T. cruzi GAPDH (rTcGAPDH) binds single-stranded telomeric DNA. We
      demonstrate that the binding of GAPDH to telomeric DNA correlates with the
      balance between oxidized and reduced forms of nicotinamide adenine dinucleotides
      (NAD+/NADH). We observed that GAPDH-telomere association and NAD+/NADH balance
      changed throughout the T. cruzi life cycle. For example, in replicative
      epimastigote forms of T. cruzi, which show similar intracellular concentrations
      of NAD+ and NADH, GAPDH binds to telomeric DNA in vivo and this binding activity
      is inhibited by exogenous NAD+. In contrast, in the T. cruzi non-proliferative
      trypomastigote forms, which show higher NAD+ concentration, GAPDH was absent from
      telomeres. In addition, NAD+ abolishes physical interaction between recombinant
      GAPDH and synthetic telomere oligonucleotide in a cell free system, mimicking
      exogenous NAD+ that reduces GAPDH-telomere interaction in vivo. We propose that
      the balance in the NAD+/NADH ratio during T. cruzi life cycle homeostatically
      regulates GAPDH telomere association, suggesting that in trypanosomes redox
      status locally modulates GAPDH association with telomeric DNA. 

PMID- 25775133
TI  - Fast-forward assisted STIRAP.
AB  - We consider combined stimulated Raman adiabatic passage (STIRAP) and fast-forward
      field (FFF) control of selective vibrational population transfer in a polyatomic
      molecule. The motivation for using this combination control scheme is 2-fold: (i)
      to overcome transfer inefficiency that occurs when the STIRAP fields and pulse
      durations must be restricted to avoid excitation of population transfers that
      compete with the targeted transfer and (ii) to overcome transfer inefficiency
      resulting from embedding of the actively driven subset of states in a large
      manifold of states. We show that, in a subset of states that is coupled to
      background states, a combination of STIRAP and FFFs that do not individually
      generate processes that are competitive with the desired population transfer can
      generate greater population transfer efficiency than can ordinary STIRAP with
      similar field strength and/or pulse duration. 

PMID- 25775132
TI  - Transcriptome analysis of the white body of the squid Euprymna tasmanica with
      emphasis on immune and hematopoietic gene discovery.
AB  - In the mutualistic relationship between the squid Euprymna tasmanica and the
      bioluminescent bacterium Vibrio fischeri, several host factors, including immune
      related proteins, are known to interact and respond specifically and exclusively
      to the presence of the symbiont. In squid and octopus, the white body is
      considered to be an immune organ mainly due to the fact that blood cells, or
      hemocytes, are known to be present in high numbers and in different developmental
      stages. Hence, the white body has been described as the site of hematopoiesis in
      cephalopods. However, to our knowledge, there are no studies showing any
      molecular evidence of such functions. In this study, we performed a
      transcriptomic analysis of white body tissue of the Southern dumpling squid, E.
      tasmanica. Our primary goal was to gain insights into the functions of this
      tissue and to test for the presence of gene transcripts associated with
      hematopoietic and immune processes. Several hematopoiesis genes including CPSF1,
      GATA 2, TFIID, and FGFR2 were found to be expressed in the white body. In
      addition, transcripts associated with immune-related signal transduction
      pathways, such as the toll-like receptor/NF-kappabeta, and MAPK pathways were
      also found, as well as other immune genes previously identified in E. tasmanica's
      sister species, E. scolopes. This study is the first to analyze an immune organ
      within cephalopods, and to provide gene expression data supporting the white body
      as a hematopoietic tissue. 

PMID- 25775134
TI  - Sensitivity analysis to aid shelter management decisions: how does altering
      expenditure affect operational viability?
AB  - Streamlining purchasing in nonhuman animal shelters can provide multiple
      financial benefits. Streamlining shelter inputs and thus reducing shelter costs
      can include trading paid labor and management for fewer, more involved volunteers
      or purchasing large quantities of medical supplies from fewer vendors to take
      advantage of bulk-purchasing discounts. Beyond direct savings, time and energy
      spent on purchasing and inventory control can be reduced through careful
      management. Although cost-cutting measures may seem attractive, shelter managers
      are cautioned to consider the potential unintended consequences of short-term
      cost reduction measures that could limit revenues or increase costs in the
      future. This analysis illustrates an example of the impact of cost reductions in
      specific expense categories and the impact on shelter net revenue, as well as the
      share of expenses across categories. An in-depth discussion of labor and
      purchasing cost-reducing strategies in the real world of animal shelter
      management is provided.

PMID- 25775136
TI  - Emerging Risks Due to New Injecting Patterns in Hungary During Austerity Times.
AB  - As a consequence of the massive restructuring of drug availability, heroin
      injection in Hungary was largely replaced by the injecting of new psychoactive
      substances (NPS) starting in 2010. In the following years in our sero-prevalence
      studies we documented higher levels of injecting paraphernalia sharing, daily
      injection-times, syringe reuse, and HCV prevalence among stimulant injectors,
      especially among NPS injectors. Despite the increasing demand, in 2012 the number
      of syringes distributed dropped by 35% due to austerity measures. Effects of drug
      market changes and the economic recession may have future epidemiological
      consequences. Study limitations are noted and future needed research is
      suggested. 

PMID- 25775135
TI  - Paradoxical effects of all-trans-retinoic acid on lupus-like disease in the
      MRL/lpr mouse model.
AB  - Roles of all-trans-retinoic acid (tRA), a metabolite of vitamin A (VA), in both
      tolerogenic and immunogenic responses are documented. However, how tRA affects
      the development of systemic autoimmunity is poorly understood. Here we
      demonstrate that tRA have paradoxical effects on the development of autoimmune
      lupus in the MRL/lpr mouse model. We administered, orally, tRA or VA mixed with
      10% of tRA (referred to as VARA) to female mice starting from 6 weeks of age. At
      this age, the mice do not exhibit overt clinical signs of lupus. However, the
      immunogenic environment preceding disease onset has been established as evidenced
      by an increase of total IgM/IgG in the plasma and expansion of lymphocytes and
      dendritic cells in secondary lymphoid organs. After 8 weeks of tRA, but not VARA
      treatment, significantly higher pathological scores in the skin, brain and lung
      were observed. These were accompanied by a marked increase in B-cell responses
      that included autoantibody production and enhanced expression of plasma cell
      promoting cytokines. Paradoxically, the number of lymphocytes in the mesenteric
      lymph node decreased with tRA that led to significantly reduced lymphadenopathy.
      In addition, tRA differentially affected renal pathology, increasing leukocyte
      infiltration of renal tubulointerstitium while restoring the size of glomeruli in
      the kidney cortex. In contrast, minimal induction of inflammation with tRA in the
      absence of an immunogenic environment in the control mice was observed.
      Altogether, our results suggest that under a predisposed immunogenic environment
      in autoimmune lupus, tRA may decrease inflammation in some organs while
      generating more severe disease in others. 

PMID- 25775137
TI  - Phosphatidylinositol 3-Kinase gamma is required for the development of
      experimental cerebral malaria.
AB  - Experimental cerebral malaria (ECM) is characterized by a strong immune response,
      with leukocyte recruitment, blood-brain barrier breakdown and hemorrhage in the
      central nervous system. Phosphatidylinositol 3-kinase gamma (PI3Kgamma) is
      central in signaling diverse cellular functions. Using PI3Kgamma-deficient mice
      (PI3Kgamma-/-) and a specific PI3Kgamma inhibitor, we investigated the relevance
      of PI3Kgamma for the outcome and the neuroinflammatory process triggered by
      Plasmodium berghei ANKA (PbA) infection. Infected PI3Kgamma-/- mice had greater
      survival despite similar parasitemia levels in comparison with infected wild type
      mice. Histopathological analysis demonstrated reduced hemorrhage, leukocyte
      accumulation and vascular obstruction in the brain of infected PI3Kgamma-/- mice.
      PI3Kgamma deficiency also presented lower microglial activation (Iba-1+ reactive
      microglia) and T cell cytotoxicity (Granzyme B expression) in the brain.
      Additionally, on day 6 post-infection, CD3+CD8+ T cells were significantly
      reduced in the brain of infected PI3Kgamma-/- mice when compared to infected wild
      type mice. Furthermore, expression of CD44 in CD8+ T cell population in the brain
      tissue and levels of phospho-IkB-alpha in the whole brain were also markedly
      lower in infected PI3Kgamma-/- mice when compared with infected wild type mice.
      Finally, AS605240, a specific PI3Kgamma inhibitor, significantly delayed
      lethality in infected wild type mice. In brief, our results indicate a pivotal
      role for PI3Kgamma in the pathogenesis of ECM. 

PMID- 25775138
TI  - Uric acid and the prediction models of tumor lysis syndrome in AML.
AB  - We investigated the ability of serum uric acid (SUA) to predict laboratory tumor
      lysis syndrome (LTLS) and compared it to common laboratory variables, cytogenetic
      profiles, tumor markers and prediction models in acute myeloid leukemia patients.
      In this retrospective study patients were risk-stratified for LTLS based on SUA
      cut-off values and the discrimination ability was compared to current prediction
      models. The incidences of LTLS were 17.8%, 21% and 62.5% in the low, intermediate
      and high-risk groups, respectively. SUA was an independent predictor of LTLS
      (adjusted OR 1.12, CI95% 1.0-1.3, p = 0.048). The discriminatory ability of SUA,
      per ROC curves, to predict LTLS was superior to LDH, cytogenetic profile, tumor
      markers and the combined model but not to WBC (AUCWBC 0.679). However, in
      comparisons between high-risk SUA and high-risk WBC, SUA had superior
      discriminatory capability than WBC (AUCSUA 0.664 vs. AUCWBC 0.520; p <0.001). SUA
      also demonstrated better performance than the prediction models (high-risk SUAAUC
      0.695, p<0.001). In direct comparison of high-risk groups, SUA again demonstrated
      superior performance than the prediction models (high-risk SUAAUC 0.668, p =
      0.001) in predicting LTLS, approaching that of the combined model (AUC 0.685,
      p<0.001). In conclusion, SUA alone is comparable and highly predictive for LTLS
      than other prediction models. 

PMID- 25775139
TI  - CYP2C9 genotype vs. metabolic phenotype for individual drug dosing--a correlation
      analysis using flurbiprofen as probe drug.
AB  - Currently, genotyping of patients for polymorphic enzymes responsible for
      metabolic elimination is considered a possibility to adjust drug dose levels. For
      a patient to profit from this procedure, the interindividual differences in drug
      metabolism within one genotype should be smaller than those between different
      genotypes. We studied a large cohort of healthy young adults (283 subjects),
      correlating their CYP2C9 genotype to a simple phenotyping metric, using
      flurbiprofen as probe drug. Genotyping was conducted for CYP2C9*1, *2, *3. The
      urinary metabolic ratio MR (concentration of CYP2C9-dependent metabolite divided
      by concentration of flurbiprofen) determined two hours after flurbiprofen (8.75
      mg) administration served as phenotyping metric. Linear statistical models
      correlating genotype and phenotype provided highly significant allele-specific MR
      estimates of 0.596 for the wild type allele CYP2C9*1, 0.405 for CYP2C9*2 (68 % of
      wild type), and 0.113 for CYP2C9*3 (19 % of wild type). If these estimates were
      used for flurbiprofen dose adjustment, taking 100 % for genotype *1/*1, an
      average reduction to 84 %, 60 %, 68 %, 43 %, and 19 % would result for genotype
      *1/*2, *1/*3, *2/*2, *2/*3, and *3/*3, respectively. Due to the large individual
      variation within genotypes with coefficients of variation >= 20 % and supposing
      the normal distribution, one in three individuals would be out of the average
      optimum dose by more than 20 %, one in 20 would be 40 % off. Whether this problem
      also applies to other CYPs and other drugs has to be investigated case by case.
      Our data for the given example, however, puts the benefit of individual drug
      dosing to question, if it is exclusively based on genotype. 

PMID- 25775140
TI  - Transmission of photonic quantum polarization entanglement in a nanoscale hybrid
      plasmonic waveguide.
AB  - Photonic quantum technologies have been extensively studied in quantum
      information science, owing to the high-speed transmission and outstanding low
      noise properties of photons. However, applications based on photonic entanglement
      are restricted due to the diffraction limit. In this work, we demonstrate for the
      first time the maintaining of quantum polarization entanglement in a nanoscale
      hybrid plasmonic waveguide composed of a fiber taper and a silver nanowire. The
      transmitted state throughout the waveguide has a fidelity of 0.932 with the
      maximally polarization entangled state Phi(+). Furthermore, the Clauser, Horne,
      Shimony, and Holt (CHSH) inequality test performed, resulting in value of 2.495
      +/- 0.147 > 2, demonstrates the violation of the hidden variable model. Because
      the plasmonic waveguide confines the effective mode area to subwavelength scale,
      it can bridge nanophotonics and quantum optics and may be used as near-field
      quantum probe in a quantum near-field micro/nanoscope, which can realize high
      spatial resolution, ultrasensitive, fiber-integrated, and plasmon-enhanced
      detection. 

PMID- 25775141
TI  - Terahertz single conductance quantum and topological phase transitions in
      topological insulator Bi2Se3 ultrathin films.
AB  - Strong spin-orbit interaction and time-reversal symmetry in topological
      insulators generate novel quantum states called topological surface states. Their
      study provides unique opportunities to explore exotic phenomena such as spin Hall
      effects and topological phase transitions, relevant to the development of quantum
      devices for spintronics and quantum computation. Although ultrahigh-vacuum
      surface probes can identify individual topological surface states, standard
      electrical and optical experiments have so far been hampered by the interference
      of bulk and quantum well states. Here, with terahertz time-domain spectroscopy of
      ultrathin Bi2Se3 films, we give evidence for topological phase transitions, a
      single conductance quantum per topological surface state, and a quantized
      terahertz absorbance of 2.9% (four times the fine structure constant). Our
      experiment demonstrates the feasibility to isolate, detect and manipulate
      topological surface states in the ambient at room temperature for future
      fundamental research on the novel physics of topological insulators and their
      practical applications.

PMID- 25775142
TI  - Arginine depletion by arginine deiminase does not affect whole protein metabolism
      or muscle fractional protein synthesis rate in mice.
AB  - Due to the absolute need for arginine that certain cancer cells have, arginine
      depletion is a therapy in clinical trials to treat several types of cancers.
      Arginine is an amino acids utilized not only as a precursor for other important
      molecules, but also for protein synthesis. Because arginine depletion can
      potentially exacerbate the progressive loss of body weight, and especially lean
      body mass, in cancer patients we determined the effect of arginine depletion by
      pegylated arginine deiminase (ADI-PEG 20) on whole body protein synthesis and
      fractional protein synthesis rate in multiple tissues of mice. ADI-PEG 20
      successfully depleted circulating arginine (<1 MUmol/L), and increased citrulline
      concentration more than tenfold. Body weight and body composition, however, were
      not affected by ADI-PEG 20. Despite the depletion of arginine, whole body protein
      synthesis and breakdown were maintained in the ADI-PEG 20 treated mice. The
      fractional protein synthesis rate of muscle was also not affected by arginine
      depletion. Most tissues (liver, kidney, spleen, heart, lungs, stomach, small and
      large intestine, pancreas) were able to maintain their fractional protein
      synthesis rate; however, the fractional protein synthesis rate of brain, thymus
      and testicles was reduced due to the ADI-PEG 20 treatment. Furthermore, these
      results were confirmed by the incorporation of ureido [14C]citrulline, which
      indicate the local conversion into arginine, into protein. In conclusion, the
      intracellular recycling pathway of citrulline is able to provide enough arginine
      to maintain protein synthesis rate and prevent the loss of lean body mass and
      body weight. 

PMID- 25775143
TI  - The two-year course of late-life depression; results from the Netherlands study
      of depression in older persons.
AB  - BACKGROUND: We aimed to examine the course of depression during 2-year follow-up
      in a group clinically depressed older persons. Subsequently, we studied which
      socio-demographic and clinical characteristics predict a depression diagnoses at
      2-year follow-up. METHODS: Data were used from the Netherlands Study of
      Depression in Older persons (NESDO; N = 510). Diagnoses of depression DSM-IV-TR
      criteria were available from 285 patients at baseline and at 2-year follow-up.
      Severity of the depressive symptoms, as assessed with the Inventory of Depressive
      Symptoms (IDS), was obtained from 6-monthly postal questionnaires. Information
      about socio-demographic and clinical variables was obtained from the baseline
      measurement. RESULT: From the 285 older persons who were clinically depressed at
      baseline almost half (48.4%) also suffered from a depressive disorder two years
      later. Patients with more severe depressive symptoms, comorbid dysthymia, younger
      age of onset and more chronic diseases were more likely to be depressed at 2-year
      follow-up. 61% of the persons that were depressed at baseline had a chronic
      course of depressive symptoms during these two years. CONCLUSIONS: Late-life
      depression often has a chronic course, even when treated conform current
      guidelines for older persons. Our results suggest that physical comorbidity may
      be candidate for adjusted and intensified treatment strategies of older depressed
      patients with chronic and complex pathology.

PMID- 25775144
TI  - Corticosteroid-sparing effect of tacrolimus in the initial treatment of
      dermatomyositis and polymyositis.
AB  - OBJECTIVE: In the treatment of polymyositis (PM) and dermatomyositis (DM), muscle
      inflammation and underlying autoimmunity need to be suppressed promptly; however,
      catabolic effects of corticosteroids such as myopathy can be detrimental in
      PM/DM. In this study, we aimed to assess the corticosteroid-sparing effect of
      tacrolimus in the initial treatment of PM/DM. METHODS: We retrospectively
      identified 19 PM/DM patients who received initial treatment with prednisolone at
      an initial dose of 1 mg/kg/day (Conventional Monotherapy, our standard therapy
      before 2008) and 23 patients with tacrolimus plus prednisolone at an initial dose
      0.8 mg/kg/day (Tacrolimus Combination, our standard therapy after 2008). Data
      until 36 months after commencing treatment were collected. RESULTS: There were no
      statistically significant differences in baseline characteristics between two
      groups. Median daily dose of prednisolone in the Tacrolimus Combination Group was
      significantly lower than that in the Conventional Monotherapy Group during the
      study period, whereas the proportion of patients who required additional
      immunosuppressive medications for remission induction was comparable. Remission
      was achieved in all patients, except one who died of refractory interstitial lung
      disease after receiving Conventional Monotherapy. The time required for creatine
      kinase normalization and relapse rate was comparable between two groups. The
      period of hospitalization for initial treatment was significantly shorter and
      survival without serious infection or relapse tended to be longer in the
      Tacrolimus Combination than the Conventional Monotherapy. CONCLUSION: This study
      provides real-life data which demonstrate that tacrolimus has a corticosteroid
      sparing effect and reduces the length of hospitalization period for the initial
      treatment of PM/DM.

PMID- 25775145
TI  - Downregulated expression of miR-155, miR-17, and miR-181b, and upregulated
      expression of activation-induced cytidine deaminase and interferon-alpha in PBMCs
      from patients with SLE.
AB  - OBJECTIVE: Recent studies on systemic lupus erythematosus (SLE) revealed that
      microRNAs (miRNAs or miRs) were involved in its pathogenesis. However, only a
      limited number of miRNAs have been examined. METHODS: We performed quantitative
      real-time reverse transcription-polymerase chain reaction analyses of peripheral
      blood mononuclear cells (PBMCs) obtained from 31 untreated SLE patients and 31
      healthy subjects to examine the expression levels of miR-155, miR-17, and miR
      181b, as well as those of activation-induced cytidine deaminase (AID) and
      interferon-alpha (IFN-alpha) messenger RNAs (mRNAs). We examined the relationship
      between miR-181b, AID, and IFN-alpha with a luciferase reporter assay. RESULTS:
      The expression levels of miR-155, miR-17, and miR-181b were significantly lower
      in SLE patients than those in healthy controls, whereas those of AID and IFN
      alpha mRNAs were significantly higher in SLE patients than those in healthy
      controls. The expression levels of miR-155, miR-17, and miR-181b inversely
      correlated with those of AID and IFN-alpha mRNAs in SLE patients. The results of
      the luciferase reporter assay revealed that miR-181b negatively regulated AID and
      IFN-alpha. CONCLUSIONS: The results of the present study demonstrated for the
      first time that there is a differential expression and inverse correlation
      between the levels the miR-155, miR-17, and miR-181b and target molecules, AID
      and IFN-alpha mRNAs, in PBMCs of untreated SLE patients. These alterations may
      contribute to the pathogenesis of SLE.

PMID- 25775146
TI  - Cervical myelopathy due to atraumatic odontoid fracture in patients with
      rheumatoid arthritis: A case series.
AB  - To highlight the risk of cervical myelopathy due to occult, atraumatic odontoid
      fracture in patients with rheumatoid arthritis, we retrospectively reviewed
      radiographic findings and clinical observations for 7 patients with this
      disorder. This fracture tends to occur in patients with long-lasting rheumatoid
      arthritis and to be misdiagnosed as simple atlantoaxial dislocation. Since this
      fracture causes multidirectional instability between C1 and C2 and is expected to
      have poor healing potential due to bone erosion and inadequate blood supply,
      posterior spinal arthrodesis surgery is indicated upon identification of the
      fracture to prevent myelopathy.

PMID- 25775147
TI  - Comparison of efficacy and safety of tacrolimus and methotrexate in combination
      with abatacept in patients with rheumatoid arthritis; a retrospective
      observational study in the TBC Registry.
AB  - OBJECTIVES: Tacrolimus (TAC) and abatacept (ABT) inhibit T-cells via different
      mechanisms and, in combination, may be effective against rheumatoid arthritis.
      However, they may also disrupt normal immune functions. We compared the efficacy
      and safety of ABT administered to patients in combination with TAC, methotrexate
      (MTX), or other drugs. METHODS: This was a retrospective multicenter study
      conducted to compare the efficacy and safety of ABT in 211 patients: the drug was
      administered together with TAC (ABT+ TAC group; 22 patients), MTX (ABT+ MTX
      group; 102 patients), or patients treated without concomitant MTX or TAC (ABT
      mono group; 87 patients). The disease activity, treatment continuation rate, and
      reason for discontinuation of treatment were investigated. RESULTS: The retention
      rate at Week 24 was similar in the three groups. There were no cases of
      discontinuation related to the appearance of adverse events in the ABT+ TAC
      group. At Week 24, according to the European League Against Rheumatism response
      criteria, the "good" response rates were 33.3%, 13.4%, and 13.4% in the ABT+ TAC,
      ABT+ MTX, and ABT mono groups, respectively. Statistically significant decreases
      in various disease activity scores/indices were observed in all the groups as
      early as Week 4. CONCLUSIONS: Although the sample size was small, the results of
      this retrospective study suggest that the ABT+ TAC combination therapy has at
      least comparable safety and efficacy to those of the ABT+ MTX combination, and
      that it can thus be a useful option for patients who cannot take MTX.

PMID- 25775148
TI  - Possible involvement of epithelial-mesenchymal transition in fibrosis associated
      with IgG4-related Mikulicz's disease.
AB  - OBJECTIVE: Immunoglobulin G4 (IgG4)-related Mikulicz's disease (MD) is a fibrosis
      associated inflammatory disease, often accompanied by lacrimal gland swelling.
      Although much attention has been paid to the inflammatory aspects of this
      disease, the mechanisms of the fibrotic processes are still unclear. We focused
      on the fibrotic changes occurring in the lacrimal glands of IgG4-related MD
      patients, by examining molecules involved in the epithelial-mesenchymal
      transition (EMT). METHODS: Lacrimal gland tissue specimens were obtained from 3
      IgG4-related MD patients and 3 control patients with Sjogren's syndrome (SS). The
      glands were examined by immunohistochemistry and transmission electron
      microscopy. RESULTS: Storiform fibrosis, a characteristic of IgG4-related MD, was
      observed in the lacrimal glands of IgG4-related MD, but rarely in those of SS.
      Reduced E-cadherin expression, increased phalloidin-stained filamentous actin,
      and increased alpha-smooth muscle actin, snail, and heat-shock protein 47 levels
      were observed in the lacrimal glands of IgG4-related MD compared with those of
      SS. Transmission electron microscopy revealed an abnormal periodicity of collagen
      bundles, and basal membrane thickening in the IgG4-related MD compared with that
      in the SS tissues. CONCLUSION: EMT-like changes were frequently observed in the
      lacrimal gland epithelia from patients with IgG4-related MD. Thus, EMT may be
      involved in the pathology of IgG4-related MD fibrosis.

PMID- 25775149
TI  - Molecular self-assembly: Best of both worlds.

PMID- 25775150
TI  - Carbon nanotube-assisted optical activation of TGF-beta signalling by near
      infrared light.
AB  - Receptor-mediated signal transduction modulates complex cellular behaviours such
      as cell growth, migration and differentiation. Although photoactivatable proteins
      have emerged as a powerful tool for controlling molecular interactions and
      signalling cascades at precise times and spaces using light, many of these light
      sensitive proteins are activated by ultraviolent or visible light, which has
      limited tissue penetration. Here, we report a single-walled carbon nanotube
      (SWCNT)-assisted approach that enables near-infrared light-triggered activation
      of transforming growth factor beta (TGF-beta) signal transduction, an important
      signalling pathway in embryonic development and cancer progression. The protein
      complex of TGF-beta and its latency-associated peptide is conjugated onto SWCNTs,
      where TGF-beta is inactive. Upon near-infrared irradiation, TGF-beta is released
      through the photothermal effect of SWCNTs and becomes active. The released TGF
      beta activates downstream signal transduction in live cells and modulates
      cellular behaviours. Furthermore, preliminary studies show that the method can be
      used to mediate TGF-beta signalling in living mice. 

PMID- 25775151
TI  - Light-emitting self-assembled peptide nucleic acids exhibit both stacking
      interactions and Watson-Crick base pairing.
AB  - The two main branches of bionanotechnology involve the self-assembly of either
      peptides or DNA. Peptide scaffolds offer chemical versatility, architectural
      flexibility and structural complexity, but they lack the precise base pairing and
      molecular recognition available with nucleic acid assemblies. Here, inspired by
      the ability of aromatic dipeptides to form ordered nanostructures with unique
      physical properties, we explore the assembly of peptide nucleic acids (PNAs),
      which are short DNA mimics that have an amide backbone. All 16 combinations of
      the very short di-PNA building blocks were synthesized and assayed for their
      ability to self-associate. Only three guanine-containing di-PNAs-CG, GC and GG
      could form ordered assemblies, as observed by electron microscopy, and these di
      PNAs efficiently assembled into discrete architectures within a few minutes. The
      X-ray crystal structure of the GC di-PNA showed the occurrence of both stacking
      interactions and Watson-Crick base pairing. The assemblies were also found to
      exhibit optical properties including voltage-dependent electroluminescence and
      wide-range excitation-dependent fluorescence in the visible region. 

PMID- 25775152
TI  - Questioning "Fluffy": A Dog's Eye View of Animal-Assisted Interventions (AAI) in
      the Treatment of Substance Misuse.

PMID- 25775153
TI  - Structural alterations of the intestinal epithelial barrier in Parkinson's
      disease.
AB  - Functional and morphological alterations of the intestinal epithelial barrier
      (IEB) have been consistently reported in digestive disorders such as irritable
      bowel syndrome and inflammatory bowel disease. There is mounting evidence that
      Parkinson's disease (PD) is not only a brain disease but also a digestive
      disorder. Gastrointestinal involvement is a frequent and early event in the
      course of PD, and it may be critically involved in the early development of the
      disease. We therefore undertook the present survey to investigate whether changes
      in the IEB function and/or morphology occur in PD. Colonic biopsies were
      performed in 31 PD patients and 11 age-matched healthy controls. The para- and
      transcellular permeability were evaluated by measuring sulfonic acid and
      horseradish peroxidase flux respectively, in colonic biopsies mounted in Ussing
      chambers. The expression and localization of the two tight junctions proteins ZO
      1 and occludin were analyzed by Western blot and immunofluorescence,
      respectively. The para- and transcellular permeability were not different between
      PD patients and controls. The expression of occludin, but not ZO-1, was
      significantly lower in colonic samples from PD patients as compared to controls
      and the cellular distribution of both proteins was altered in colonic mucosal
      specimens from PD patients. Our findings provide evidence that the IEB is
      morphologically altered in PD and further reinforce the potential role of the
      gastrointestinal tract in the initiation and/or the progression of the disease. 

PMID- 25775154
TI  - Genome-wide identification and analysis of drought-responsive genes and microRNAs
      in tobacco.
AB  - Drought stress response is a complex trait regulated at transcriptional and post
      transcriptional levels in tobacco. Since the 1990s, many studies have shown that
      miRNAs act in many ways to regulate target expression in plant growth,
      development and stress response. The recent draft genome sequence of Nicotiana
      benthamiana has provided a framework for Digital Gene Expression (DGE) and small
      RNA sequencing to understand patterns of transcription in the context of plant
      response to environmental stress. We sequenced and analyzed three Digital Gene
      Expression (DGE) libraries from roots of normal and drought-stressed tobacco
      plants, and four small RNA populations from roots, stems and leaves of control or
      drought-treated tobacco plants, respectively. We identified 276 candidate drought
      responsive genes (DRGs) with sequence similarities to 64 known DRGs from other
      model plant crops, 82 were transcription factors (TFs) including WRKY, NAC, ERF
      and bZIP families. Of these tobacco DRGs, 54 differentially expressed DRGs
      included 21 TFs, which belonged to 4 TF families such as NAC (6), MYB (4), ERF
      (10), and bZIP (1). Additionally, we confirmed expression of 39 known miRNA
      families (122 members) and five conserved miRNA families, which showed
      differential regulation under drought stress. Targets of miRNAs were further
      surveyed based on a recently published study, of which ten targets were DRGs. An
      integrated gene regulatory network is proposed for the molecular mechanisms of
      tobacco root response to drought stress using differentially expressed DRGs, the
      changed expression profiles of miRNAs and their target transcripts. This network
      analysis serves as a reference for future studies on tobacco response stresses
      such as drought, cold and heavy metals. 

PMID- 25775155
TI  - The importance of G protein-coupled receptor kinase 4 (GRK4) in pathogenesis of
      salt sensitivity, salt sensitive hypertension and response to antihypertensive
      treatment.
AB  - Salt sensitivity is probably caused by either a hereditary or acquired defect of
      salt excretion by the kidney, and it is reasonable to consider that this is the
      basis for differences in hypertension between black and white people. Dopamine
      acts in an autocrine/paracrine fashion to promote natriuresis in the proximal
      tubule and thick ascending loop of Henle. G-protein receptor kinases (or GRKs)
      are serine and threonine kinases that phosphorylate G protein-coupled receptors
      in response to agonist stimulation and uncouple the dopamine receptor from its G
      protein. This results in a desensitisation process that protects the cell from
      repeated agonist exposure. GRK4 activity is increased in spontaneously
      hypertensive rats, and infusion of GRK4 antisense oligonucleotides attenuates the
      increase in blood pressure (BP). This functional defect is replicated in the
      proximal tubule by expression of GRK4 variants namely p.Arg65Leu, p.Ala142Val and
      p.Val486Ala, in cell lines, with the p.Ala142Val showing the most activity. In
      humans, GRK4 polymorphisms were shown to be associated with essential
      hypertension in Australia, BP regulation in young adults, low renin hypertension
      in Japan and impaired stress-induced Na excretion in normotensive black men. In
      South Africa, GRK4 polymorphisms are more common in people of African descent,
      associated with impaired Na excretion in normotensive African people, and predict
      blood pressure response to Na restriction in African patients with mild to
      moderate essential hypertension. The therapeutic importance of the GRK4 single
      nucleotide polymorphisms (SNPs) was emphasised in the African American Study of
      Kidney Disease (AASK) where African-Americans with hypertensive nephrosclerosis
      were randomised to receive amlodipine, ramipril or metoprolol. Men with the
      p.Ala142Val genotype were less likely to respond to metoprolol, especially if
      they also had the p.Arg65Leu variant. Furthermore, in the analysis of response to
      treatment in two major hypertension studies, the 65Leu/142Val heterozygote
      predicted a significantly decreased response to atenolol treatment, and the
      65Leu/142Val heterozygote and 486Val homozygote were associated in an additive
      fashion with adverse cardiovascular outcomes, independent of BP. In conclusion,
      there is considerable evidence that GRK4 variants are linked to impaired Na
      excretion, hypertension in animal models and humans, therapeutic response to
      dietary Na restriction and response to antihypertensive drugs. It may also
      underlie the difference in hypertension between different geographically derived
      population groups, and form a basis for pharmacogenomic approaches to treatment
      of hypertension. 

PMID- 25775156
TI  - Anti-TMV activity of malformin A1, a cyclic penta-peptide produced by an
      endophytic fungus Aspergillus tubingensis FJBJ11.
AB  - Plant-associated microorganisms are known to produce a variety of metabolites
      with novel structures and interesting biological activities. An endophytic fungus
      FJBJ11, isolated from the plant tissue of Brucea javanica (L.) Merr.
      (Simaroubaceae), was proven to be significantly effective in producing
      metabolites with anti-Tobacco mosaic virus (TMV) activities. The isolate was
      identified as Aspergillus tubingensis FJBJ11 based on morphological
      characteristics and ITS sequence. Bioassay-guided isolation led to the
      identification of a cycli penta-peptide, malformin A1, along with two cyclic
      dipeptides, cyclo (Gly-L-Pro) and cyclo (Ala-Leu). Malformin A1 showed potent
      inhibitory effect against the infection and replication of TMV with IC50 values
      of 19.7 and 45.4 MUg.mL-1, as tested using local lesion assay and leaf-disc
      method, respectively. The results indicated the potential use of malformin A1 as
      a leading compound or a promising candidate of new viricide.

PMID- 25775157
TI  - Phenolic composition and antioxidant properties of different peach [Prunus
      persica (L.) Batsch] cultivars in China.
AB  - China is an important centre of diversity for Prunus persica. In the present
      study, 17 Chinese peach cultivars were evaluated for phenolic content and
      antioxidant activity. Neochlorogenic acid (NCHA), chlorogenic acid (CHA),
      procyanidin B1 (B1), catechin (CAT), cyanidin-3-O-glucoside (C3G), quercetin-3-O
      galactoside (Q3GAL), quercetin-3-O-glucoside (Q3GLU), quercetin-3-O-rutinoside
      (Q3R), and kaempferol-3-O-rutinoside (K3R) were identified and quantified. CHA
      and CAT were the predominant components in both the peel and pulp of this fruit.
      In general, peel extracts showed higher antioxidant activities than the pulp
      counterparts, consistent with the observed higher phenolic content. The melting
      peach cultivar "Xinyu" showed the highest antioxidant potency composite (APC)
      index. The principal component analysis (PCA) of peel phenolics showed a clear
      distinction between the melting peach and nectarine. Overall, peach cultivars
      rich in hydroxycinnamates and flavan-3-ols showed relatively higher antioxidant
      activities and might be excellent sources of phytochemicals and natural
      antioxidants. 

PMID- 25775158
TI  - Biomechanical evaluation of Ti-Nb-Sn alloy implants with a low Young's modulus.
AB  - Dental implants are widely used and are a predictable treatment in various
      edentulous cases. Occlusal overload may be causally related to implant bone loss
      and a loss of integration. Stress concentrations may be diminished using a
      mechanobiologically integrated implant with bone tissue. The purpose of this
      study was to investigate the biomechanical behavior, biocompatibility and
      bioactivity of a Ti-Nb-Sn alloy as a dental implant material. It was compared
      with cpTi. Cell proliferation and alkaline phosphatase (ALP) activity were
      quantified. To assess the degree of osseointegration, a push-in test was carried
      out. Cell proliferation and ALP activity in the cells grown on prepared surfaces
      were similar for the Ti-Nb-Sn alloy and for cpTi in all the experiments. A
      comparison between the Ti-Nb-Sn alloy implant and the cpTi implant revealed that
      no significant difference was apparent for the push-in test values. These results
      suggest that implants fabricated using Ti-Nb-Sn have a similar biological
      potential as cpTi and are capable of excellent osseointegration. 

PMID- 25775159
TI  - Protective effects of resveratrol against UVA-induced damage in ARPE19 cells.
AB  - Ultraviolet radiation, especially UVA, can penetrate the lens, reach the retina,
      and induce oxidative stress to retinal pigment epithelial (RPE) cells. Even
      though it is weakly absorbed by protein and DNA, it may trigger the production of
      reactive oxygen species (ROS) and generate oxidative injury; oxidative injury to
      the retinal pigment epithelium has been implicated to play a contributory role in
      age-related macular degeneration (AMD). Studies showed that resveratrol, an
      abundant and active component of red grapes, can protect several cell types from
      oxidative stress. In this study, adult RPE cells being treated with different
      concentrations of resveratrol were used to evaluate the protective effect of
      resveratrol on RPE cells against UVA-induced damage. Cell viability assay showed
      that resveratrol reduced the UVA-induced decrease in RPE cell viability. Through
      flow cytometry analysis, we found that the generation of intracellular H2O2
      induced by UVA irradiation in RPE cells could be suppressed by resveratrol in a
      concentration-dependent manner. Results of Western blot analysis demonstrated
      that resveratrol lowered the activation of UVA-induced extracellular signal
      regulated kinase, c-jun-NH2 terminal kinase and p38 kinase in RPE cells. In
      addition, there was also a reduction in UVA-induced cyclooxygenase-2 (COX-2)
      expression in RPE cells pretreated with resveratrol. Our observations suggest
      that resveratrol is effective in preventing RPE cells from being damaged by UVA
      radiation, and is worth considering for further development as a chemoprotective
      agent for the prevention of early AMD. 

PMID- 25775160
TI  - Methodologies and perspectives of proteomics applied to filamentous fungi: from
      sample preparation to secretome analysis.
AB  - Filamentous fungi possess the extraordinary ability to digest complex biomasses
      and mineralize numerous xenobiotics, as consequence of their aptitude to sensing
      the environment and regulating their intra and extra cellular proteins, producing
      drastic changes in proteome and secretome composition. Recent advancement in
      proteomic technologies offers an exciting opportunity to reveal the fluctuations
      of fungal proteins and enzymes, responsible for their metabolic adaptation to a
      large variety of environmental conditions. Here, an overview of the most commonly
      used proteomic strategies will be provided; this paper will range from sample
      preparation to gel-free and gel-based proteomics, discussing pros and cons of
      each mentioned state-of-the-art technique. The main focus will be kept on
      filamentous fungi. Due to the biotechnological relevance of lignocellulose
      degrading fungi, special attention will be finally given to their extracellular
      proteome, or secretome. Secreted proteins and enzymes will be discussed in
      relation to their involvement in bio-based processes, such as biomass
      deconstruction and mycoremediation. 

PMID- 25775161
TI  - A pharmacogenetics study in Mozambican patients treated with nevirapine: full
      resequencing of TRAF3IP2 gene shows a novel association with SJS/TEN
      susceptibility.
AB  - Steven-Johnson Syndrome (SJS) and Toxic Epidermal Necrolysis (TEN) are severe
      adverse drug reactions, characterized by extensive epidermal detachment and
      erosions of mucous membrane. SJS/TEN is one of the most serious adverse reactions
      to Nevirapine (NVP) treatment, commonly used in developing countries as first
      line treatment of human immunodeficiency virus infection. In the last years
      TRAF3IP2 gene variants had been described as associated with susceptibility to
      several diseases such as psoriasis and psoriatic arthritis. We hypothesized that
      this gene, involved in immune response and in NF-kappaB activation, could also be
      implicated in the SJS/TEN susceptibility. We performed a full resequencing of
      TRAF3IP2 gene in a population of patients treated with NVP. Twenty-seven patients
      with NVP-induced SJS/TEN and 78 controls, all from Mozambique, were enrolled. We
      identified eight exonic and three intronic already described variants. The
      case/control association analysis highlighted an association between the
      rs76228616 SNP in exon 2 and the SJS/TEN susceptibility. In particular, the
      variant allele (C) resulted significantly associated with a higher risk to
      develop SJS/TEN (p = 0.012 and OR = 3.65 (95% CI 1.33-10.01)). A multivariate
      analysis by logistic regression confirmed its significant contribution (p =
      0.027, OR = 4.39 (95% CI 1.19-16.23)). In conclusion, our study suggests that a
      variant in TRAF3IP2 gene could be involved in susceptibility to SJS/TEN. 

PMID- 25775163
TI  - Effect of published scientific evidence on glycemic control in adult intensive
      care units.
AB  - IMPORTANCE: Little is known about the deadoption of ineffective or harmful
      clinical practices. A large clinical trial (the Normoglycemia in Intensive Care
      Evaluation and Survival Using Glucose Algorithm Regulation [NICE-SUGAR] trial)
      demonstrated that strict blood glucose control (tight glycemic control) in
      patients admitted to adult intensive care units (ICUs) should be deadopted;
      however, it is unknown whether deadoption occurred and how it compared with the
      initial adoption. OBJECTIVE: To evaluate glycemic control in critically ill
      patients before and after the publication of clinical trials that initially
      suggested that tight glycemic control reduced mortality (Leuven I) but
      subsequently demonstrated that it increased mortality (NICE-SUGAR). DESIGN,
      SETTING, AND PARTICIPANTS: Interrupted time-series analysis of 353,464 patients
      admitted to 113 adult ICUs from January 1, 2001, through December 31, 2012, in
      the United States using data from the Acute Physiology and Chronic Health
      Evaluation database. MAIN OUTCOMES AND MEASURES: The physiologically most extreme
      blood glucose level on day 1 of ICU admission defined glycemic control as tight
      control (glucose level, 80-110 mg/dL; to convert to millimoles per liter,
      multiply by 0.0555), hypoglycemia (glucose level, <70 mg/dL), and hyperglycemia
      (glucose level, >=180 mg/dL). Temporal changes in each marker were examined using
      mixed-effects segmented linear regression. RESULTS: Before the publication of
      Leuven I, 17.2% (95% CI, 16.2%-18.2%) of ICU admissions had tight glycemic
      control, 3.0% (95% CI, 2.6%-3.5%) had hypoglycemia, and 40.2% (95% CI, 38.8%
      41.5%) had hyperglycemia. After the publication of Leuven I, there were
      significant increases in the relative proportion of admissions with tight
      glycemic control (1.7% per quarter; 95% CI, 1.2%-2.3%; P<.001) and hypoglycemia
      (2.5% per quarter; 95% CI, 1.9%-3.2%; P<.001) and decreases in those with
      hyperglycemia (0.6% per quarter; 95% CI, 0.4%-0.9%; P<.001). Following the
      publication of NICE-SUGAR, there was no change in the proportion of patients with
      tight glycemic control or hyperglycemia. There was an immediate decrease in the
      relative proportion of patients with hypoglycemia (22.4%; 95% CI, 13.2%-30.1%;
      P<.001) but no subsequent change over time. CONCLUSIONS AND RELEVANCE: Among
      patients admitted to adult ICUs in the United States, there was a slow steady
      adoption of tight glycemic control following publication of a clinical trial that
      suggested benefit, with little to no deadoption following a subsequent trial that
      demonstrated harm. There is an urgent need to understand and promote the
      deadoption of ineffective clinical practices.

PMID- 25775164
TI  - Structural and evolutionary versatility in protein complexes with uneven
      stoichiometry.
AB  - Proteins assemble into complexes with diverse quaternary structures. Although
      most heteromeric complexes of known structure have even stoichiometry, a
      significant minority have uneven stoichiometry--that is, differing numbers of
      each subunit type. To adopt this uneven stoichiometry, sequence-identical
      subunits must be asymmetric with respect to each other, forming different
      interactions within the complex. Here we first investigate the occurrence of
      uneven stoichiometry, demonstrating that it is common in vitro and is likely to
      be common in vivo. Next, we elucidate the structural determinants of uneven
      stoichiometry, identifying six different mechanisms by which it can be achieved.
      Finally, we study the frequency of uneven stoichiometry across evolution,
      observing a significant enrichment in bacteria compared with eukaryotes. We show
      that this arises due to a general increased tendency for bacterial proteins to
      self-assemble and form homomeric interactions, even within the context of a
      heteromeric complex.

PMID- 25775162
TI  - The CENP-T C-terminus is exclusively proximal to H3.1 and not to H3.2 or H3.3.
AB  - The kinetochore proteins assemble onto centromeric chromatin and regulate DNA
      segregation during cell division. The inner kinetochore proteins bind centromeres
      while most outer kinetochore proteins assemble at centromeres during mitosis,
      connecting the complex to microtubules. The centromere-kinetochore complex
      contains specific nucleosomes and nucleosomal particles. CENP-A replaces
      canonical H3 in centromeric nucleosomes, defining centromeric chromatin. Next to
      CENP-A, the CCAN multi-protein complex settles which contains CENP-T/W/S/X. These
      four proteins are described to form a nucleosomal particle at centromeres. We had
      found the CENP-T C-terminus and the CENP-S termini next to histone H3.1 but not
      to CENP-A, suggesting that the Constitutive Centromere-Associated Network (CCAN)
      bridges a CENP-A- and a H3-containing nucleosome. Here, we show by in vivo FRET
      that this proximity between CENP-T and H3 is specific for H3.1 but neither for
      the H3.1 mutants H3.1(C96A) and H3.1(C110A) nor for H3.2 or H3.3. We also found
      CENP-M next to H3.1 but not to these H3.1 mutants. Consistently, we detected CENP
      M next to CENP-S. These data elucidate the local molecular neighborhood of CCAN
      proteins next to a H3.1-containing centromeric nucleosome. They also indicate an
      exclusive position of H3.1 clearly distinct from H3.2, thus documenting a local,
      and potentially also functional, difference between H3.1 and H3.2.

PMID- 25775166
TI  - Current progress in 3D printing for cardiovascular tissue engineering.
AB  - 3D printing is a technology that allows the fabrication of structures with
      arbitrary geometries and heterogeneous material properties. The application of
      this technology to biological structures that match the complexity of native
      tissue is of great interest to researchers. This mini-review highlights the
      current progress of 3D printing for fabricating artificial tissues of the
      cardiovascular system, specifically the myocardium, heart valves, and coronary
      arteries. In addition, how 3D printed sensors and actuators can play a role in
      tissue engineering is discussed. To date, all the work with building 3D cardiac
      tissues have been proof-of-principle demonstrations, and in most cases, yielded
      products less effective than other traditional tissue engineering strategies.
      However, this technology is in its infancy and therefore there is much promise
      that through collaboration between biologists, engineers and material scientists,
      3D bioprinting can make a significant impact on the field of cardiovascular
      tissue engineering. 

PMID- 25775167
TI  - Predicting Reduction of Cerebrospinal Fluid beta-Amyloid 42 in Cognitively
      Healthy Controls.
AB  - IMPORTANCE: Alzheimer disease has a long preclinical stage characterized by beta
      amyloid (Abeta) accumulation without symptoms. Several trials focus on this stage
      and use biomarkers to include Abeta-positive participants, but an even earlier
      prevention of Abeta accumulation may be an effective treatment strategy.
      OBJECTIVE: To determine whether people who appear to be Abeta negative but are at
      high risk for Abeta positivity within the near future can be identified. DESIGN,
      SETTING, AND PARTICIPANTS: Longitudinal biomarker cohort study involving 35
      cognitively healthy individuals who underwent cerebrospinal fluid (CSF) sampling
      for up to 3 years during the study (October 24, 2005, to September 1, 2014). All
      participants had normal CSF Abeta42 levels at baseline. MAIN OUTCOMES AND
      MEASURES: Predictors of future Abeta positivity (levels of CSF Abeta42 declining
      below a previously validated cutoff level of 192 ng/L) tested by random forest
      models. Tested predictors included levels of protein in the CSF, hippocampal
      volume, genetics, demographics, and cognitive scores. RESULTS: The CSF Abeta42
      levels declined in 11 participants, and the CSF became Abeta positive. The
      baseline CSF Abeta42 level was a strong predictor of future positivity (accuracy,
      79% [95% CI, 70%-87%]). Ten of 11 decliners had baseline CSF Abeta42 levels in
      the lower tertile of the reference range (<225 ng/L), and 22 of 24 nondecliners
      had baseline CSF Abeta42 levels in the upper 2 tertiles (>=225 ng/L). A high CSF
      P-tau level was associated with decline (accuracy, 68%; 95% CI, 55%-81%).
      CONCLUSIONS AND RELEVANCE: Baseline CSF Abeta42 levels in the lower part of the
      reference range are strongly associated with future Abeta positivity. This
      finding can be used in trials on very early prevention of Alzheimer disease to
      identify people at high risk for Abeta accumulation as defined by low CSF Abeta42
      levels.

PMID- 25775169
TI  - The imbalance between matrix metalloproteinase 9 and tissue inhibitor of
      metalloproteinase 1 in acute pancreatitis.
AB  - BACKGROUND: The balanced activity of matrix metalloproteinases and their tissue
      inhibitors is an important, albeit still not completely understood, determinant
      of extracellular matrix homeostasis, a factor involved in the pathogenesis of
      acute pancreatitis (AP). AIMS: The aim of this study was to compare serum
      concentrations of matrix metalloproteinase 9 (MMP-9) and its tissue inhibitor
      (TIMP-1) in patients with AP of various severity and to investigate their
      relationship with prognostic indicators of AP severity, e.g., polymorphonuclear
      leukocyte elastase (PMN-E). PATIENTS AND METHODS: The study included 37 patients
      with mild (n = 18) or severe AP (n = 19) and 15 healthy controls. Serum
      concentrations of MMP-9 and TIMP-1 were determined on admission (day 1) and on
      days 2, 3, 5 and 10. RESULTS: Throughout the study period, the serum MMP-9
      concentration in patients with severe AP was significantly higher than those in
      individuals with mild AP and in healthy controls. In turn, the serum MMP-9
      concentrations in persons with mild AP did not differ significantly from those of
      the controls. The serum TIMP-1 concentrations in both groups were significantly
      higher than in the controls. Beginning from the 2(nd) day of hospital stay, the
      serum TIMP-1 concentration in patients with severe AP was significantly higher
      than in individuals with mild AP. There were significant correlations between:
      MMP-9 and PMN-E, TIMP-1 and PMN-E, and MMP-9 and TIMP-1. CONCLUSION: A disturbed
      balance between MMP-9 and TIMP-1 observed during the early stages of severe AP
      suggests that endogenous TIMP-1 is unable to prevent excessive activation and
      release of MMP-9. MMP-9 may represent a new marker of AP severity.

PMID- 25775170
TI  - [OTSC-assisted resection of a duodenal neuroendocrine tumor: a case report].
AB  - The over the scope clip (OTSC) is mainly used for closure of gastrointestinal
      endoluminal defects and treatment of gastrointestinal bleeding. Its use for
      resection of subepithelial tumors or full-thickness resection is still under
      investigation. Duodenal neuroendocrine tumors (NET) are rare neoplasms.
      Endoscopic resection is appropriate up to a size of 20  mm, however positive deep
      margins are a frequent challenge in these subepithelial tumors. We report on a 60
      year-old male patient who had undergone endoscopic mucosal resection with R1 deep
      margins of a NET (G1) in the duodenal bulb. To avoid local surgical resection in
      this multimorbid patient, we performed OTSC-assisted deep resection. Complete
      resection (R0) was achieved, and no complications occurred. Our report suggests
      that OTSC-assisted resection of subepithelial tumors is a possible and safe
      option, especially for patient's and in locations with a high perioperative risk.

PMID- 25775171
TI  - [Ultrasound of the thyroid].
AB  - Thyroid nodules and thyroid abnormalities are common findings in the general
      population. Ultrasonography is the most important imaging tool for diagnosing
      thyroid disease. In the majority of cases a correct diagnosis can already be made
      in synopsis of the sonographic together with clinical findings and basal thyroid
      hormone parameters and an appropriate therapy can be initiated thereafter. A
      differentiation of hormonally active versus inactive nodes, and in particular
      benign versus malignant nodules is sonographically, however, not reliably
      possible. In this context, radioscanning has its clinical significance
      predominantly in diagnosing hormonal activity of thyroid nodules. Efforts of the
      past years aimed to improve sonographic risk stratification to predict malignancy
      of thyroid nodules through standardized diagnostic assessment of evaluated risk
      factors in order to select patients, who need further diagnostic work up.
      According to the "Breast Imaging Reporting and Data System" (BI-RADS), "Thyroid
      Imaging Reporting and Data Systems" (TI-RADS) giving standardized categories with
      rates of malignancy were evaluated as a basis for further clinical management.
      Recent technological developments, such as elastography, also show promising data
      and could gain entrance into clinical practice. The ultrasound-guided fine-needle
      aspiration is the key element in the diagnosis of sonographically suspicious
      thyroid nodules and significantly contributes to the diagnosis of malignancy
      versus benignity.

PMID- 25775165
TI  - Depressive symptoms, antidepressant medication use, and new onset of diabetes in
      participants of the diabetes prevention program and the diabetes prevention
      program outcomes study.
AB  - OBJECTIVE: To assess in the Diabetes Prevention Program and Diabetes Prevention
      Program Outcomes Study whether diagnosis of diabetes predicted elevated
      depressive symptoms (DS) or use of antidepressant medicine (ADM) following
      diagnosis; whether diabetes status or duration had significant effect on DS or
      ADM use; and to determine the associations between A1C, fasting plasma glucose
      (FPG), normalization of FPG, and DS or ADM use after diagnosis. METHODS: Diabetes
      Prevention Program participants in three treatment arms (intensive life style,
      metformin, placebo) were assessed for diabetes, glucose control, ADM use, and DS,
      measured using the Beck Depression Inventory (BDI). Among 3234 participants, 1285
      developed diabetes. Depression levels were measured before and after diabetes
      diagnosis. RESULTS: Neither DS nor use of ADM increased after diagnosis; higher
      FPG was associated with greater ADM use in the intensive life style arm; a 10
      mg/dl rise in FPG is associated with greater odds of ADM use. Higher FPG and A1C
      were associated with higher BDI scores in all three arms; A 10-mg/dl rise in FPG
      had a 0.07 increase in BDI. A 1% higher A1c was associated with a 0.21-point
      increase in BDI. Normalization of FPG was associated with lower BDI. When FPG had
      normalized, there was a decrease of 0.30 points in the BDI score compared when
      FPG had not normalized. CONCLUSIONS: Contrary to clinical attributions, diabetes
      diagnosis did not show an immediate impact on BDI scores or ADM use. Higher
      glucose levels after diagnosis were associated with a small but significantly
      higher BDI score and more ADM use. TRIAL REGISTRATION: DPPOS: NCT00038727; DPP:
      NCT00004992.

PMID- 25775172
TI  - [Gastrointestinal stromal tumours (GIST)--development in pathology, surgery and
      medical therapy. Developed during the 10th German GIST-meeting, Gottingen].
AB  - The first description of ligand-independent activating mutations in the KIT gene,
      which encodes the tyrosine-kinase KIT, greatly improved our understanding of
      gastrointestinal stromal tumour (GIST) biology. The therapeutic success in GIST
      has made tyrosine kinase inhibitors a "paradigm of targeted therapy". Deciphering
      resistance mechanisms in GIST has had implications for many other kinase-driven
      cancers. To exchange current knowledge within the field of GIST, the German GIST
      Meeting has taken place for now 10 years, traditionally in Gottingen. Subjects
      discussed include clinical diagnostics, pathology, surgery, and medical therapy.
      The following presentation gives an overview of the last meeting held in December
      2013, including distinctive features in GIST and current data on the different
      topics. 

PMID- 25775173
TI  - [Early or late enteral nutrition in severe acute pancreatitis?].

PMID- 25775174
TI  - Spatiotemporal predictability alters perceived duration of visual events: Memento
      effect revisited.
AB  - Does event perception alter perceived duration? Previous research has shown that
      the perceived duration of a short scene depicting a disk moving along a segmented
      path is reduced when the temporal order of the motion segments is reversed
      (Memento effect). This effect has been attributed to the idea that reversed
      segments give rise to the perception of distinct visual events, whereas
      continuous segments are perceived as a single event. It has been suggested that
      the reduction in perceived duration is a result of perceiving multiple distinct
      events rather than 1. Here, the authors replicate and investigate the origin of
      the Memento effect. In 4 experiments, they explore the role of the spatiotemporal
      predictability of the disk's movement as well as the influence of the number of
      discrete events on perceived duration. Controlling for spatiotemporal
      predictability eliminates the Memento effect; however, controlling for the number
      of distinct events does not. Thus, the authors' results suggest that violations
      in spatiotemporal predictability rather than a varying number of discrete events
      induce the Memento effect. The authors discuss the impact of these findings for
      the perception of more naturalistic events.

PMID- 25775175
TI  - A crossmodal role for audition in taste perception.
AB  - Our sense of taste can be influenced by our other senses, with several groups
      having explored the effects of olfactory, visual, or tactile stimulation on what
      we perceive as taste. Research into multisensory, or crossmodal perception has
      rarely linked our sense of taste with that of audition. In our study, 48
      participants in a crossover experiment sampled multiple concentrations of
      solutions of 5 prototypic tastants, during conditions with or without broad
      spectrum auditory stimulation, simulating that of airline cabin noise. Airline
      cabins are an unusual environment, in which food is consumed routinely under
      extreme noise conditions, often over 85 dB, and in which the perceived quality of
      food is often criticized. Participants rated the intensity of solutions
      representing varying concentrations of the 5 basic tastes on the general Labeled
      Magnitude Scale. No difference in intensity ratings was evident between the
      control and sound condition for salty, sour, or bitter tastes. Likewise,
      panelists did not perform differently during sound conditions when rating
      tactile, visual, or auditory stimulation, or in reaction time tests.
      Interestingly, sweet taste intensity was rated progressively lower, whereas the
      perception of umami taste was augmented during the experimental sound condition,
      to a progressively greater degree with increasing concentration. We postulate
      that this effect arises from mechanostimulation of the chorda tympani nerve,
      which transits directly across the tympanic membrane of the middle ear.

PMID- 25775176
TI  - More than accuracy: Nonverbal dialects modulate the time course of vocal emotion
      recognition across cultures.
AB  - Using a gating paradigm, this study investigated the nature of the in-group
      advantage in vocal emotion recognition by comparing 2 distinct cultures.
      Pseudoutterances conveying 4 basic emotions, expressed in English and Hindi, were
      presented to English and Hindi listeners. In addition to hearing full utterances,
      each stimulus was gated from its onset to construct 5 processing intervals to
      pinpoint when the in-group advantage emerges, and whether this differs when
      listening to a foreign language (English participants judging Hindi) or a second
      language (Hindi participants judging English). An index of the mean emotion
      identification point for each group and unbiased measures of accuracy at each
      time point was calculated. Results showed that in each language condition, native
      listeners were faster and more accurate than non-native listeners to recognize
      emotions. The in-group advantage emerged in both conditions after processing 400
      ms to 500 ms of acoustic information. In the bilingual Hindi group, greater oral
      proficiency in English predicted faster and more accurate recognition of English
      emotional expressions. Consistent with dialect theory, our findings provide new
      evidence that nonverbal dialects impede both the accuracy and the efficiency of
      vocal emotion processing in cross-cultural settings, even when individuals are
      highly proficient in the out-group target language.

PMID- 25775168
TI  - [Improvement of cost allocation in gastroenterology by introduction of a novel
      service catalogue covering the complete spectrum of endoscopic procedures].
AB  - BACKGROUND: The German hospital reimbursement system (G-DRG) is incomplete for
      endoscopic interventions and fails to differentiate between complex and simple
      procedures. This is caused by outdated methods of personnel-cost allocation.
      METHODS: To establish an up-to-date service catalogue 50 hospitals made their
      anonymized expense-budget data available to the German-Society-of
      Gastroenterology (DGVS). 2.499.900 patient-datasets (2011-2013) were used to
      classify operation-and-procedure codes (OPS) into procedure-tiers (e.g.
      colonoscopy with biopsy/colonoscopy with stent-insertion). An expert panel ranked
      these tiers according to complexity and assigned estimates of physician time.
      From June to November 2014 exact time tracking data for a total 38.288 individual
      procedures were collected in 119 hospitals to validate this service catalogue.
      RESULTS: In this three-step process a catalogue of 97 procedure-tiers was
      established that covers 99% of endoscopic interventions performed in German
      hospitals and assigned validated mean personnel-costs using gastroscopy as
      standard. Previously, diagnostic colonoscopy had a relative personnel-cost value
      of 1.13 (compared to gastroscopy 1.0) and rose to 2.16, whereas diagnostic ERCP
      increased from 1.7 to 3.62, more appropriately reflecting complexity. Complex
      procedures previously not catalogued were now included (e.g. gastric endoscopic
      submucosal dissection: 16.74). DISCUSSION: This novel service catalogue for GI
      endoscopy almost completely covers all endoscopic procedures performed in German
      hospitals and assigns relative personnel-cost values based on actual physician
      time logs. It is to be included in the national coding recommendation and should
      replace all prior inventories for cost distribution. The catalogue will
      contribute to a more objective cost allocation and hospital reimbursement - at
      least until time tracking for endoscopy becomes mandatory.

PMID- 25775178
TI  - Severe Intraoperative Hemodynamic Disturbances--A Potential Complication of
      Cranioplasty.

PMID- 25775177
TI  - Novel type II and monomeric NAD+ specific isocitrate dehydrogenases: phylogenetic
      affinity, enzymatic characterization, and evolutionary implication.
AB  - NAD(+) use is an ancestral trait of isocitrate dehydrogenase (IDH), and the
      NADP(+) phenotype arose through evolution as an ancient adaptation event.
      However, no NAD(+)-specific IDHs have been found among type II IDHs and monomeric
      IDHs. In this study, novel type II homodimeric NAD-IDHs from Ostreococcus
      lucimarinus CCE9901 IDH (OlIDH) and Micromonas sp. RCC299 (MiIDH), and novel
      monomeric NAD-IDHs from Campylobacter sp. FOBRC14 IDH (CaIDH) and Campylobacter
      curvus (CcIDH) were reported for the first time. The homodimeric OlIDH and
      monomeric CaIDH were determined by size exclusion chromatography and MALDI
      TOF/TOF mass spectrometry. All the four IDHs were demonstrated to be NAD(+)
      specific, since OlIDH, MiIDH, CaIDH and CcIDH displayed 99-fold, 224-fold, 61
      fold and 37-fold preferences for NAD(+) over NADP(+), respectively. The putative
      coenzyme discriminating amino acids (Asp326/Met327 in OlIDH, Leu584/Asp595 in
      CaIDH) were evaluated, and the coenzyme specificities of the two mutants, OlIDH
      R(326)H(327) and CaIDH H(584)R(595), were completely reversed from NAD(+) to
      NADP(+). The detailed biochemical properties, including optimal reaction pH and
      temperature, thermostability, and metal ion effects, of OlIDH and CaIDH were
      further investigated. The evolutionary connections among OlIDH, CaIDH, and all
      the other forms of IDHs were described and discussed thoroughly. 

PMID- 25775179
TI  - Revision of Ventriculoatrial Shunt With Transesophageal Echocardiogram Guidance.

PMID- 25775180
TI  - Prevention of obesity in infancy and early childhood: a National Institutes of
      Health workshop.
AB  - Addressing the childhood obesity epidemic continues to be a challenge. Given that
      once obesity develops it is likely to persist, there has been an increasing focus
      on prevention at earlier stages of the life course. Research to develop and
      implement effective prevention and intervention strategies in the first 2 years
      after birth has been limited. In fall 2013, the National Institute of Diabetes
      and Digestive and Kidney Diseases convened a multidisciplinary workshop to
      summarize the current state of knowledge regarding the prevention of infant and
      early childhood obesity and to identify research gaps and opportunities. The
      questions addressed included (1) "What is known regarding risk for excess weight
      gain in infancy and early childhood?" (2) "What is known regarding interventions
      that are promising or have been shown to be efficacious?" and (3) "What are the
      challenges and opportunities in implementing and evaluating behavioral
      interventions for parents and other caregivers and their young children?" 

PMID- 25775181
TI  - ER quality control components UGGT and STT3a are required for activation of
      defense responses in bir1-1.
AB  - The receptor-like kinase SUPPRESSOR OF BIR1, 1 (SOBIR1) functions as a critical
      regulator in plant immunity. It is required for activation of cell death and
      defense responses in Arabidopsis bak1-interacting receptor-like kinase 1,1 (bir1
      1) mutant plants. Here we report that the ER quality control component UDP
      glucose:glycoprotein glucosyltransferase (UGGT) is required for the biogenesis of
      SOBIR1 and mutations in UGGT suppress the spontaneous cell death and constitutive
      defense responses in bir1-1. Loss of function of STT3a, which encodes a subunit
      of the oligosaccharyltransferase complex, also suppresses the autoimmune
      phenotype in bir1-1. However, it has no effect on the accumulation of SOBIR1,
      suggesting that additional signaling components other than SOBIR1 may be
      regulated by ER quality control. Our study provides clear evidence that ER
      quality control play critical roles in regulating defense activation in bir1-1. 

PMID- 25775182
TI  - Partitioning detectability components in populations subject to within-season
      temporary emigration using binomial mixture models.
AB  - Detectability of individual animals is highly variable and nearly always < 1;
      imperfect detection must be accounted for to reliably estimate population sizes
      and trends. Hierarchical models can simultaneously estimate abundance and
      effective detection probability, but there are several different mechanisms that
      cause variation in detectability. Neglecting temporary emigration can lead to
      biased population estimates because availability and conditional detection
      probability are confounded. In this study, we extend previous hierarchical
      binomial mixture models to account for multiple sources of variation in
      detectability. The state process of the hierarchical model describes ecological
      mechanisms that generate spatial and temporal patterns in abundance, while the
      observation model accounts for the imperfect nature of counting individuals due
      to temporary emigration and false absences. We illustrate our model's potential
      advantages, including the allowance of temporary emigration between sampling
      periods, with a case study of southern red-backed salamanders Plethodon serratus.
      We fit our model and a standard binomial mixture model to counts of terrestrial
      salamanders surveyed at 40 sites during 3-5 surveys each spring and fall 2010
      2012. Our models generated similar parameter estimates to standard binomial
      mixture models. Aspect was the best predictor of salamander abundance in our case
      study; abundance increased as aspect became more northeasterly. Increased time
      since-rainfall strongly decreased salamander surface activity (i.e. availability
      for sampling), while higher amounts of woody cover objects and rocks increased
      conditional detection probability (i.e. probability of capture, given an animal
      is exposed to sampling). By explicitly accounting for both components of
      detectability, we increased congruence between our statistical modeling and our
      ecological understanding of the system. We stress the importance of choosing
      survey locations and protocols that maximize species availability and conditional
      detection probability to increase population parameter estimate reliability. 

PMID- 25775183
TI  - Interpreting the results of the targeted temperature management trial in cardiac
      arrest.
AB  - The targeted temperature management (TTM) trial, which found that cooling to 33
      degrees C after witnessed cardiac arrest (CA) conferred no benefits compared with
      36 degrees C, has led to much debate in the hypothermia community. This article
      discusses what lessons can be drawn. The TTM trial achieved far better outcomes
      in controls than any previous randomized controlled trial (RCT) or any
      nonrandomized study where no fever control was applied. On the other hand, rates
      of good outcomes in the hypothermia group were somewhat lower than in previous
      RCTs and most nonrandomized studies. The TTM authors conclude that benefits of
      temperature management are derived exclusively from fever control and that
      further lowering of temperature confers no benefit. Indeed, without doubt, the
      TTM trial demonstrates the crucial importance of strict fever control after CA
      and that this provides sufficient neuroprotection for some patients. However, we
      argue that the hypothermia intervention was executed suboptimally (possibly
      inadvertent selection bias; late start of cooling, up to 4 hours after ROSC; slow
      cooling rates, 10 hours to target temperature; more rapid rewarming than previous
      studies; and some other issues). This could explain high rates of good outcomes
      in controls and lower-than-expected rates in patients cooled to 33 degrees C
      compared with previous randomized and nonrandomized studies. Outside of two
      previous RCTs, the use of hypothermia after CA is supported by hundreds of animal
      experiments, evidence from 46 before-after studies and large registries, and
      indirect supporting evidence from 7 RCTs in newborns with neonatal asphyxia. In
      addition, one RCT found improved outcomes with 32 degrees C compared with 34
      degrees C. It remains to be explained why the TTM results so completely
      contradict previous studies in this field. These issues should be thoroughly
      discussed before changes in guidelines and protocols are made. Ending or
      modifying hypothermia treatment after CA should require the strongest possible
      evidence.

PMID- 25775184
TI  - Unintentional activation of translation equivalents in bilinguals leads to
      attention capture in a cross-modal visual task.
AB  - Using a variant of the visual world eye tracking paradigm, we examined if
      language non-selective activation of translation equivalents leads to attention
      capture and distraction in a visual task in bilinguals. High and low proficient
      Hindi-English speaking bilinguals were instructed to programme a saccade towards
      a line drawing which changed colour among other distractor objects. A spoken
      word, irrelevant to the main task, was presented before the colour change. On
      critical trials, one of the line drawings was a phonologically related word of
      the translation equivalent of the spoken word. Results showed that saccade
      latency was significantly higher towards the target in the presence of this cross
      linguistic translation competitor compared to when the display contained
      completely unrelated objects. Participants were also slower when the display
      contained the referent of the spoken word among the distractors. However, the
      bilingual groups did not differ with regard to the interference effect observed.
      These findings suggest that spoken words activates translation equivalent which
      bias attention leading to interference in goal directed action in the visual
      domain.

PMID- 25775185
TI  - Physical therapies in the management of osteoarthritis: current state of the
      evidence.
AB  - PURPOSE OF REVIEW: This review considers the role of physical therapies in
      osteoarthritis management, highlighting key findings from systematic reviews and
      randomized controlled trials published in the last 2 years. RECENT FINDINGS:
      Three new trials question the role of manual therapy for hip and knee
      osteoarthritis. No between-group differences in outcome were detected between a
      multimodal programme including manual therapy and home exercise, and placebo in
      one trial; a second trial found no benefit of adding manual therapy to an
      exercise programme, while a third trial reported marginal benefits over usual
      care that were of doubtful importance. Recent trials have also found no or
      uncertain clinical benefits of transcutaneous electrical nerve stimulation (TENS)
      or acupuncture, or of valgus braces or lateral wedge insoles for pain and
      function in knee osteoarthritis. Available evidence suggests a small to moderate
      effect of exercise in comparison with not exercising for hip or knee
      osteoarthritis, although optimum exercise prescription and dosage are unclear.
      One trial also observed a delay in joint replacement in people with hip
      osteoarthritis. Two trials have reported conflicting findings about the effects
      of exercise for hand osteoarthritis. SUMMARY: Other than exercise, recent data
      suggest that the role of physical therapies in the treatment of osteoarthritis
      appears limited.

PMID- 25775187
TI  - Can antineutrophil cytoplasmic antibody levels be used to inform treatment of
      pauci-immune vasculitis?
AB  - PURPOSE OF REVIEW: The role of serial antineutrophil cytoplasmic antibody (ANCA)
      measurements to guide immunosuppressive therapy in pauci-immune vasculitis is an
      area of ongoing controversy. Evidence elucidating the relationship between ANCA
      levels and disease activity continues to grow. RECENT FINDINGS: The finding that
      proteinase 3-ANCA and myeloperoxidase-ANCA-associated diseases differ genetically
      has challenged the traditional classification and study of pauci-immune
      vasculitis. Multiple studies have also found that the clinical features and
      course of disease differ by ANCA antigen specificity more than clinical
      diagnosis. Advances in diagnostic assays and new techniques for the evaluation of
      ANCA levels over time have yielded improved assay performance in specific subsets
      of patients. In addition, increasing use of rituximab has added to our
      understanding of the relationship of ANCA levels to B-cell counts and disease
      relapse, which may differ by treatment regimen. SUMMARY: The relationship between
      ANCA levels and disease activity is impacted by multiple factors, including
      antigen specificity, disease manifestations, clinical assay, and therapeutic
      regimen. Each of these must be taken into account when determining the
      significance of ANCA levels during long-term follow-up of pauci-immune
      vasculitis.

PMID- 25775186
TI  - State of the evidence.
AB  - PURPOSE OF REVIEW: This review focuses on recent studies of osteoarthritis
      epidemiology, including research on prevalence, incidence, and a broad array of
      potential risk factors at the person level and joint level. RECENT FINDINGS:
      Studies continue to illustrate the high impact of osteoarthritis worldwide, with
      increasing incidence. Person-level risk factors with strong evidence regarding
      osteoarthritis incidence and/or progression include age, sex, socioeconomic
      status, family history, and obesity. Joint-level risk factors with strong
      evidence for incident osteoarthritis risk include injury and occupational joint
      loading; the associations of injury and joint alignment with osteoarthritis
      progression are compelling. Moderate levels of physical activity have not been
      linked to increased osteoarthritis risk. Some topics of high recent interest or
      emerging evidence for association with osteoarthritis include metabolic pathways,
      vitamins, joint shape, bone density, limb length inequality, muscle strength and
      mass, and early structural damage. SUMMARY: Osteoarthritis is a complex,
      multifactorial disease, and there is still much to learn regarding mechanisms
      underlying incidence and progression. However, there are several known modifiable
      and preventable risk factors, including obesity and joint injury; efforts to
      mitigate these risks can help to lessen the impact of osteoarthritis.

PMID- 25775188
TI  - Genetic contribution to osteoarthritis development: current state of evidence.
AB  - PURPOSE OF REVIEW: Powerful association studies have identified a number of
      genetic signals that can be confidently judged as associated with osteoarthritis.
      Efforts have continued to discover new loci, whilst functional studies are being
      applied to assess which genes are the likely targets of the risk-conferring
      alleles. The study of epigenetics has highlighted an interaction between
      osteoarthritis genetics and DNA methylation. This review will summarize some of
      the recent key studies in osteoarthritis genetics, including functional and
      epigenetic analyses. RECENT FINDINGS: Several novel osteoarthritis susceptibility
      loci have been reported recently, including the regulatory genes NCOA3 and
      ALDH1A2. Functional analyses of these genes and of others reported previously
      support earlier suggestions that osteoarthritis susceptibility is principally
      mediated by modulations to gene expression. DNA methylation analyses provide
      additional insights into the osteoarthritis disease process, at both a genome
      wide level and when investigating direct interactions with risk-conferring
      alleles. SUMMARY: Osteoarthritis genetic risk predominantly acts by modulating
      gene expression, an effect typically mediated via transcriptional regulation.
      Effects on various pathways have been detected, including cell differentiation
      and cartilage homeostasis. The continued identification of risk loci, their
      functional study, and the unification of genetic and epigenetic analyses will be
      key themes in the future.

PMID- 25775189
TI  - New pathogenic insights into rheumatoid arthritis.
AB  - PURPOSE OF REVIEW: Rheumatoid arthritis (RA) is a heterogeneous chronic immune
      mediated inflammatory disease, associated with significant morbidity and reduced
      life expectancy. Here, we review recent discoveries; particularly those which
      have attempted to integrate genome-wide association studies (GWAS) with
      biological pathways and cell types known to play a role in disease pathology in
      order to expand our current understanding of the pathogenesis of RA. As the role
      of stromal cells in the pathogenesis of RA has been reviewed in detail in Current
      Opinions in Rheumatology, this area will not be covered in this review. RECENT
      FINDINGS: Although our understandings of the pathogenic processes that drive
      disease in RA remain incomplete, remarkable advances over the past year can be
      highlighted. GWAS have raised awareness of important new risk loci with genes
      that either are the targets of approved therapies for RA, or involve pathways for
      drugs that could be repurposed from other disease indications such as cancer.
      Furthermore, promising strides have been made in predicting the likelihood of
      developing RA in those at risk using human leukocyte antigen (HLA), smoking, and
      autoantibody status prediction models. These findings give a fresh insight into
      RA pathogenesis and help identify new, or repurpose known therapeutic targets
      from other disease areas. SUMMARY: The findings discussed in this review
      underscore the progress made to date and the need for future studies,
      investigating disease mechanisms in RA, with particular interest in at-risk RA
      gene loci, their function in immune and stromal cells within the synovium, and
      how they interact with environmental factors to initiate and perpetuate disease.

PMID- 25775190
TI  - Systemic sclerosis: a systematic review on therapeutic management from 2011 to
      2014.
AB  - PURPOSE OF REVIEW: To review pharmacologic and nonpharmacologic therapies in the
      treatment of systemic sclerosis (SSc) from 2011 to 2014 through a systematic
      review. RECENT FINDINGS: Our systematic review identifies randomized controlled
      trials, meta-analyses, systematic reviews, case series, and observational studies
      which support organ-based therapy with known immunosuppressive agents, novel
      agents, and hematopoietic stem cell transplantation, and also includes
      nonpharmacologic therapies improving visceral and physical function. SUMMARY: SSc
      is an orphan autoimmune disorder with significant morbidity and mortality.
      Although there has been significant progress over the years in therapeutic
      options for SSc, the mainstays of treatment are organ-based and primarily symptom
      management. Our systematic review of the last 4 years of treatment emphasizes
      known treatment strategies already in practice, but also identifies new
      therapeutic approaches with additional biologic agents and hematopoietic stem
      cell transplantation.

PMID- 25775191
TI  - Genetic dissection of grain size and grain number trade-offs in CIMMYT wheat
      germplasm.
AB  - Grain weight (GW) and number per unit area of land (GN) are the primary
      components of grain yield in wheat. In segregating populations both yield
      components often show a negative correlation among themselves. Here we use a
      recombinant doubled haploid population of 105 individuals developed from the
      CIMMYT varieties Weebill and Bacanora to understand the relative contribution of
      these components to grain yield and their interaction with each other. Weebill
      was chosen for its high GW and Bacanora for high GN. The population was
      phenotyped in Mexico, Argentina, Chile and the UK. Two loci influencing grain
      yield were indicated on 1B and 7B after QTL analysis. Weebill contributed the
      increasing alleles. The 1B effect, which is probably caused by to the 1BL.1RS rye
      introgression in Bacanora, was a result of increased GN, whereas, the 7B QTL
      controls GW. We concluded that increased in GW from Weebill 7B allele is not
      accompanied by a significant reduction in grain number. The extent of the GW and
      GN trade-off is reduced. This makes this locus an attractive target for marker
      assisted selection to develop high yielding bold grain varieties like Weebill.
      AMMI analysis was used to show that the 7B Weebill allele appears to contribute
      to yield stability. 

PMID- 25775192
TI  - Ocular pharmacokinetics comparison between 0.2% olopatadine and 0.77% olopatadine
      hydrochloride ophthalmic solutions administered to male New Zealand white
      rabbits.
AB  - PURPOSE: The primary objective of this study was to compare uptake and
      distribution of the commercially available formulation of 0.2% olopatadine and
      the newly developed 0.77% olopatadine hydrochloride ophthalmic solution
      formulation with improved solubility following a single (30 MUL), bilateral
      topical ocular dose in male New Zealand white rabbits. METHODS: Each animal
      received a single 30-MUL topical ocular dose (0.2% olopatadine or 0.77%
      olopatadine hydrochloride ophthalmic solution) to the right (OD) eye followed by
      the left (OS) eye for a total dose of 60 MUL. Olopatadine concentrations were
      measured in ocular tissues (cornea, bulbar, conjunctiva, choroid, iris-ciliary
      body, whole lens, retina), aqueous humor, and plasma at prespecified time points
      over 24 h using a qualified liquid chromatography coupled with mass spectrometry
      (LC-MS/MS) analytical method. RESULTS: Olopatadine was absorbed into the eye and
      reached maximal levels (Cmax) within 30 min (0.5 h) to 2 h (Tmax) in ocular
      tissues and plasma for both treatment groups, except for the lens in which the
      Tmax was 4 h in the 0.2% olopatadine group and 8 h in the 0.77% olopatadine
      hydrochloride group, respectively. Tissues associated with the site of dosing,
      that is, the conjunctiva and cornea, had the highest concentrations of
      olopatadine in both the 0.2% olopatadine (609 and 720 ng/g) and 0.77% olopatadine
      hydrochloride (3,000 and 2,230 ng/g) dose groups. The greatest differences
      between 0.2% olopatadine and 0.77% olopatadine hydrochloride were associated with
      the overall duration and level of ocular exposures. CONCLUSIONS: The newly
      developed 0.77% olopatadine hydrochloride ophthalmic solution formulation
      resulted in a higher and more prolonged olopatadine concentration in the target
      tissue, that is, conjunctiva compared to the commercial formulation of 0.2%
      olopatadine ophthalmic solution.

PMID- 25775194
TI  - Radiologically Guided Placement of Mushroom-retained Gastrostomy Catheters: Long
      term Outcomes of Use in 300 Patients at a Single Center.
AB  - PURPOSE: To assess long-term outcomes including risk of complications and
      nutritional benefits of mushroom-retained (pull-type) gastrostomy catheters
      placed in patients by interventional radiologists. MATERIALS AND METHODS: All
      patients who received pull-type gastrostomy tubes between 2010 and 2013 were
      retrospectively reviewed, including 142 men (average weight, 169.6 lb [76.32 kg];
      mean age, 65.2 years; range, 22-92 years) and 158 women (average weight, 150.4 lb
      [67.68 kg]; mean age, 65.2 years; range, 18-98 years). Indications for placement
      were cerebrovascular accident (n = 80), failure to thrive (n = 71), other central
      nervous system disorder (n = 51), head and neck cancer (n = 47), and other
      malignancy (n = 51). Complications were recorded per Society of Interventional
      Radiology practice guidelines. Patient weight was documented at specific follow
      up intervals. Statistical analysis was performed by using the Student t test and
      one-way analysis of variance for the effects of sex and indication for placement,
      respectively, on average weight change. RESULTS: The technical success rate was
      98.4% (300 of 305 patients). Major and minor complications occurred at a rate of
      3.7% (n = 11) and 13% (n = 39), respectively. Follow-up weight during the early
      (<=45 days), intermediate (<=180 days), and long-term (>180 days) periods was
      available for 71% (n = 214), 36% (n = 108), and 15% (n = 44) of the 300 patients,
      respectively. Weight gain occurred in 77% (160 of 214), 60% (65 of 108), and 73%
      (32 of 44) of the patients, respectively. Patients who gained weight gained 6.7,
      10.6, and 16.3 lb (3.02, 4.77, and 7.34 kg) during each follow-up period,
      respectively. Average weight gain at follow-up in all patients was 4.2, 0.6, and
      5.4 lb (1.89, 0.27, and 2.43 kg), respectively. No significant differences in
      average weight change were seen among groups when they were classified according
      to sex or indication for placement. CONCLUSION: Placement of mushroom-retained
      gastrostomy catheters is a viable long-term treatment option for enteral
      nutrition, with complication rates similar to those reported for other
      gastrostomy techniques. Improvement in nutrition status measured as weight gain
      was seen in most patients in both early and long-term periods.

PMID- 25775193
TI  - TINTIN, at the interface of chromatin, transcription elongation, and mRNA
      processing.
AB  - Recent work including high-resolution genome-wide analysis uncovered a new
      trimeric complex involved in transcription elongation, both as an integral part
      of the NuA4 histone acetyltransferase and as an independent functional entity.
      The complex is conserved in eukaryotes and is named TINTIN, for Trimer
      Independent of NuA4 for transcription Interactions with Nucleosomes. This point
      of view covers the current knowledge regarding TINTIN's function in modulating
      chromatin structure and influencing transcription elongation in eukaryotes. It
      also points to several physical and functional links to co-transcriptional
      processes, including interactions with the mRNA splicing machinery and the
      nuclear exosome. 

PMID- 25775195
TI  - The sarcopenia-dynapenia dilemma: exercise is the adjunct link in the nutritional
      pathway.

PMID- 25775198
TI  - Hyperbaric oxygen therapy prior authorization: not an April Fool's joke!

PMID- 25775199
TI  - Modalities of soft-tissue coverage in diabetic foot ulcers.
AB  - OBJECTIVE: The objective of this study was to establish an algorithm for surgical
      reconstruction of diabetic foot ulcers (DFUs). STUDY DESIGN: Retrospective study
      MATERIALS AND METHODS: : In this series, 75 patients with diabetic foot
      ulceration were treated at the Jawaharlal Nehru Medical College from October 2008
      to August 2013, and were retrospectively reviewed. All patients in the study
      underwent surgical reconstruction of the foot in the form of a skin graft, local
      flaps, or free flaps, depending upon the characteristic of the defect, general
      condition of the patient, and vascular status of the limb. The medical notes of
      the patients were retrospectively analyzed according to age, gender, ankle
      brachial pressure index, and comorbidities. RESULTS: Twenty-eight patients (37%)
      underwent skin grafting, 39 (52%) underwent local pedicled flaps, and 8 (11%)
      underwent free flap transfers. Sixty-eight patients (91%) achieved complete
      healing, and amputation of the lower extremity could be avoided. With the
      exception of 1 patient who experienced ulcer recurrence within the following year
      and 6 patients in whom amputation of the lower extremity was performed, all
      patients healed completely. The mean hospital stay was 4.0 +/- 1 week.
      CONCLUSIONS: From the results of this study, the authors conclude that radical
      debridement and soft-tissue cover in the form of a skin graft/flap is an
      effective method of managing DFUs.

PMID- 25775200
TI  - Treatment options for venous leg ulcers: effectiveness of vascular surgery,
      bioengineered tissue, and electrical stimulation.
AB  - OBJECTIVE: To evaluate the peer-reviewed literature that compares advanced venous
      leg ulcer therapies to standard of care with compression dressings. METHODS: A
      MEDLINE search for venous ulcer treatment with electrical stimulation, surgical
      vein correction, and bioengineered tissues was conducted. Randomized clinical
      trials comparing advanced treatment with standard of care using compression
      dressing were included. A total of 7 bioengineered tissue, 4 surgical treatment,
      and 4 electrical stimulation randomized clinical trials were identified. RESULTS:
      Compared with nonstandard treatments, electrical stimulation demonstrated
      improved wound healing, fewer adverse events, and shorter duration of healing.
      Healing rates at the end of the study were greater for surgical intervention,
      followed by similar outcomes for electrical stimulation and bioengineered
      tissues. Studies involving bioengineered tissues and surgical venous ablation
      demonstrated inconsistent/inconclusive results. CONCLUSIONS: Utilization of
      electrical stimulation in venous ulcer management has not been fully explored.
      Further studies of dosing electrical stimulation therapy may reveal therapeutic
      and preventive benefits for managing venous ulcers not yet elucidated.

PMID- 25775201
TI  - The role of nutrition for pressure ulcer management: national pressure ulcer
      advisory panel, European pressure ulcer advisory panel, and pan pacific pressure
      injury alliance white paper.
AB  - Nutrition and hydration play an important role in preserving skin and tissue
      viability and in supporting tissue repair for pressure ulcer (PrU) healing. The
      majority of research investigating the relationship between nutrition and wounds
      focuses on PrUs. This white paper reviews the 2014 National Pressure Ulcer
      Advisory Panel, European Pressure Ulcer Advisory Panel, and Pan Pacific Pressure
      Injury Alliance Nutrition Guidelines and discusses nutrition strategies for PrU
      management.

PMID- 25775203
TI  - Clinical order sets: defining laboratory tests for pressure ulcers.

PMID- 25775204
TI  - Sub-parts per million NO2 chemi-transistor sensors based on composite porous
      silicon/gold nanostructures prepared by metal-assisted etching.
AB  - Surface doping of nano/mesostructured materials with metal nanoparticles to
      promote and optimize chemi-transistor sensing performance represents the most
      advanced research trend in the field of solid-state chemical sensing. In spite of
      the promising results emerging from metal-doping of a number of nanostructured
      semiconductors, its applicability to silicon-based chemi-transistor sensors has
      been hindered so far by the difficulties in integrating the composite metal
      silicon nanostructures using the complementary metal-oxide-semiconductor (CMOS)
      technology. Here we propose a facile and effective top-down method for the high
      yield fabrication of chemi-transistor sensors making use of composite porous
      silicon/gold nanostructures (cSiAuNs) acting as sensing gate. In particular, we
      investigate the integration of cSiAuNs synthesized by metal-assisted etching
      (MAE), using gold nanoparticles (NPs) as catalyst, in solid-state junction-field
      effect transistors (JFETs), aimed at the detection of NO2 down to 100 parts per
      billion (ppb). The chemi-transistor sensors, namely cSiAuJFETs, are CMOS
      compatible, operate at room temperature, and are reliable, sensitive, and fully
      recoverable for the detection of NO2 at concentrations between 100 and 500 ppb,
      up to 48 h of continuous operation. 

PMID- 25775205
TI  - Accuracy of preimplantation genetic diagnosis in equine in vivo-recovered and in
      vitro-produced blastocysts.
AB  - Preimplantation genetic diagnosis has great potential in the horse, but
      information on evaluation of equine embryo biopsy samples is limited. Blastocysts
      were biopsied using a Piezo drill and methods for whole-genome amplification
      (WGA) investigated. Results for 33 genetic loci were then compared between biopsy
      samples from in vitro-produced (IVP) and in vivo-recovered (VIV) blastocysts.
      Under the experimental conditions described, WGA using the Qiagen Repli-g Midi
      kit was more accurate than that using the Illustra Genomiphi V2 kit (98.2% vs
      25.8%, respectively). Using WGA with the Qiagen kit, three biopsy samples were
      evaluated from each of eight IVP and 19 VIV blastocysts, some produced using
      semen from stallions carrying the genetic mutations associated with the diseases
      hereditary equine regional dermal asthenia (HERDA), hyperkalemic periodic
      paralysis (HYPP) or polysaccharide storage myopathy 1 (PSSM1). Three of 81 biopsy
      samples (3.7%) returned 95% overall accuracy in IVP and VIV embryos, and this
      technique is suitable for use in a clinical setting.

PMID- 25775207
TI  - Highlights in lymphoma from the 2014 American Society of Hematology annual
      meeting and exposition.

PMID- 25775206
TI  - Developing a Research Career Focusing on a Stigmatized and Marginalized
      Population: Sexual Minority Women's Drinking.

PMID- 25775209
TI  - Analysis of silver nanoparticles in antimicrobial products using surface-enhanced
      Raman spectroscopy (SERS).
AB  - Silver nanoparticles (AgNPs) are the most commonly used nanoparticles in consumer
      products. Concerns over human exposure to and risk from these particles have
      resulted in increased interest in novel strategies to detect AgNPs. This study
      investigated the feasibility of surface-enhanced Raman spectroscopy (SERS) as a
      method for the detection and quantification of AgNPs in antimicrobial products.
      By using ferbam (ferric dimethyl-dithiocarbamate) as an indicator molecule that
      binds strongly onto the nanoparticles, AgNPs detection and discrimination were
      achieved based on the signature SERS response of AgNPs-ferbam complexes. SERS
      response with ferbam was distinct for silver ions, silver chloride, silver bulk
      particles, and AgNPs. Two types of AgNPs with different coatings, citrate and
      polyvinylpirrolidone (PVP), both showed strong interactions with ferbam and
      induced strong SERS signals. SERS was effectively applicable for detecting Ag
      particles ranging from 20 to 200 nm, with the highest signal intensity in the 60
      100 nm range. A linear relationship (R(2) = 0.9804) between Raman intensity and
      citrate-AgNPs concentrations (60 nm; 0-20 mg/L) indicates the potential for
      particle quantification. We also evaluated SERS detection of AgNPs in four
      commercially available antimicrobial products. Combined with ICP-MS and TEM data,
      the results indicated that the SERS response is primarily dependent on size, but
      also affected by AgNPs concentration. The findings demonstrate that SERS is a
      promising analytical platform for studying environmentally relevant levels of
      AgNPs in consumer products and related matrices. 

PMID- 25775210
TI  - Age-dependent changes in intrinsic neuronal excitability in subiculum after
      status epilepticus.
AB  - Kainic acid-induced status epilepticus (KA-SE) in mature rats results in the
      development of spontaneous recurrent seizures and a pattern of cell death
      resembling hippocampal sclerosis in patients with temporal lobe epilepsy. In
      contrast, KA-SE in young animals before postnatal day (P) 18 is less likely to
      cause cell death or epilepsy. To investigate whether changes in neuronal
      excitability occur in the subiculum after KA-SE, we examined the age-dependent
      effects of SE on the bursting neurons of subiculum, the major output region of
      the hippocampus. Patch-clamp recordings were used to monitor bursting in
      pyramidal neurons in the subiculum of rat hippocampal slices. Neurons were
      studied either one or 2-3 weeks following injection of KA or saline (control) in
      immature (P15) or more mature (P30) rats, which differ in their sensitivity to KA
      as well as the long-term sequelae of the KA-SE. A significantly greater
      proportion of subicular pyramidal neurons from P15 rats were strong-bursting
      neurons and showed increased frequency-dependent bursting compared to P30
      animals. Frequency-dependent burst firing was enhanced in P30, but not in P15
      rats following KA-SE. The enhancement of bursting induced by KA-SE in more mature
      rats suggests that the frequency-dependent limitation of repetitive burst firing,
      which normally occurs in the subiculum, is compromised following SE. These
      changes could facilitate the initiation of spontaneous recurrent seizures or
      their spread from the hippocampus to other parts of the brain. 

PMID- 25775212
TI  - Opportunity for natural selection among five population groups of Manipur, North
      East India.
AB  - Opportunity for natural selection among five population groups of Manipur in
      comparison with other North East Indian population has been studied. Crow's index
      as well as Johnston and Kensinger's index for natural selection were calculated
      based on differential fertility and mortality. The mortality component was found
      to be lower compared to fertility component in all the populations which may
      attribute to comparatively improved and easily accessible health care facilities.
      However, different selection pressures, artificial and natural, seem to be
      influencing the selection intensity through induced abortion and spontaneous
      abortion among the two non-tribal migrant groups: Bamon and Muslims,
      respectively. This study highlights the probable interaction of artificial and
      natural selection in determining the evolutionary fate of any population group. 

PMID- 25775211
TI  - Functional significance of calcium binding to tissue-nonspecific alkaline
      phosphatase.
AB  - The conserved active site of alkaline phosphatases (AP) contains catalytically
      important Zn2+ (M1 and M2) and Mg2+-sites (M3) and a fourth peripheral Ca2+ site
      (M4) of unknown significance. We have studied Ca2+ binding to M1-4 of tissue
      nonspecific AP (TNAP), an enzyme crucial for skeletal mineralization, using
      recombinant TNAP and a series of M4 mutants. Ca2+ could substitute for Mg2+ at
      M3, with maximal activity for Ca2+/Zn2+-TNAP around 40% that of Mg2+/Zn2+-TNAP at
      pH 9.8 and 7.4. At pH 7.4, allosteric TNAP-activation at M3 by Ca2+ occurred
      faster than by Mg2+. Several TNAP M4 mutations eradicated TNAP activity, while
      others mildly influenced the affinity of Ca2+ and Mg2+ for M3 similarly,
      excluding a catalytic role for Ca2+ in the TNAP M4 site. At pH 9.8, Ca2+ competed
      with soluble Zn2+ for binding to M1 and M2 up to 1 mM and at higher
      concentrations, it even displaced M1- and M2-bound Zn2+, forming Ca2+/Ca2+-TNAP
      with a catalytic activity only 4-6% that of Mg2+/Zn2+-TNAP. At pH 7.4,
      competition with Zn2+ and its displacement from M1 and M2 required >10-fold
      higher Ca2+ concentrations, to generate weakly active Ca2+/Ca2+-TNAP. Thus, in a
      Ca2+-rich environment, such as during skeletal mineralization at pH 7.4, Ca2+
      adequately activates Zn2+-TNAP at M3, but very high Ca2+ concentrations compete
      with available Zn2+ for binding to M1 and M2 and ultimately displace Zn2+ from
      the active site, virtually inactivating TNAP. Those ALPL mutations that
      substitute critical TNAP amino acids involved in coordinating Ca2+ to M4 cause
      hypophosphatasia because of their 3D-structural impact, but M4-bound Ca2+ is
      catalytically inactive. In conclusion, during skeletal mineralization, the
      building Ca2+ gradient first activates TNAP, but gradually inactivates it at high
      Ca2+ concentrations, toward completion of mineralization. 

PMID- 25775213
TI  - Development of the Multidimensional Peer Victimization Scale-Revised (MPVS-R) and
      the Multidimensional Peer Bullying Scale (MPVS-RB).
AB  - Peer victimization is a frequent occurrence for many adolescents; however, some
      of the psychometric properties of self-report scales assessing these experiences
      remain unclear. Furthermore, with an increase in access to technology, electronic
      aggression should also be considered. The authors examined the psychometric
      properties of the Multidimensional Peer Victimization Scale (MPVS; Mynard &
      Joseph, 2000), and developed versions to include the assessment of electronic
      aggression according to whether the adolescent was the target or perpetrator of
      peer victimization. A total of 371 (191 girls and 180 boys; Mage = 13 years 4
      months, SDage = 1 year 2 months) adolescents in the United Kingdom completed the
      MPVS including five newly developed items assessing electronic aggression, a
      version of the MPVS designed to assess victimization perpetration, and a measure
      of self-esteem. Confirmatory factor analyses yielded a five-factor structure
      comprising: Physical, social manipulation, verbal, attacks on property, and
      electronic for both scales. Convergent validity was established through negative
      associations between the victimization scales and self-esteem. Sex differences
      also emerged. One revised scale and one new scale are subsequently proposed: The
      MPVS-Revised and the Multidimensional Peer Bullying Scale. 

PMID- 25775214
TI  - Hyperdiverse gene cluster in snail host conveys resistance to human schistosome
      parasites.
AB  - Schistosomiasis, a neglected global pandemic, may be curtailed by blocking
      transmission of the parasite via its intermediate hosts, aquatic snails.
      Elucidating the genetic basis of snail-schistosome interaction is a key to this
      strategy. Here we map a natural parasite-resistance polymorphism from a Caribbean
      population of the snail Biomphalaria glabrata. In independent experimental
      evolution lines, RAD genotyping shows that the same genomic region responds to
      selection for resistance to the parasite Schistosoma mansoni. A dominant allele
      in this region conveys an 8-fold decrease in the odds of infection. Fine-mapping
      and RNA-Seq characterization reveal a <1Mb region, the Guadeloupe Resistance
      Complex (GRC), with 15 coding genes. Seven genes are single-pass transmembrane
      proteins with putative immunological roles, most of which show strikingly high
      nonsynonymous divergence (5-10%) among alleles. High linkage disequilibrium among
      three intermediate-frequency (>25%) haplotypes across the GRC, a significantly
      non-neutral pattern, suggests that balancing selection maintains diversity at the
      GRC. Thus, the GRC resembles immune gene complexes seen in other taxa and is
      likely involved in parasite recognition. The GRC is a potential target for
      controlling transmission of schistosomiasis, including via genetic manipulation
      of snails. 

PMID- 25775216
TI  - From the synthesis of specifically labelled radioactive tracers to the pattern
      analysis of naturally labelled compounds - a personal perspective.

PMID- 25775215
TI  - IL-13 induces YY1 through the AKT pathway in lung fibroblasts.
AB  - A key feature of lung fibrosis is the accumulation of myofibroblasts. Interleukin
      13 (IL-13) is a pro-fibrotic mediator that directly and indirectly influences the
      activation of myofibroblasts. Transforming growth factor beta (TGF-beta) promotes
      the differentiation of fibroblasts into myofibroblasts, and can be regulated by
      IL-13. However, IL-13's downstream signaling pathways are not completely
      understood. We previously reported that the transcription factor Yin Yang 1 (YY1)
      is upregulated in fibroblasts treated with TGF-beta and in the lungs of mice and
      patients with pulmonary fibrosis. Moreover, YY1 directly regulates collagen and
      alpha smooth muscle actin (alpha-SMA) expression in fibroblasts. However, it is
      not known if IL-13 regulates fibroblast activation through YY1 expression. We
      hypothesize that IL-13 up-regulates YY1 expression through regulation of AKT
      activation, leading to fibroblast activation. In this study we found that YY1 was
      upregulated by IL-13 in lung fibroblasts in a dose- and time-dependent manner,
      resulting in increased alpha-SMA. Conversely, knockdown of YY1 blocked IL-13
      induced alpha-SMA expression in fibroblasts. Furthermore, AKT phosphorylation was
      increased in fibroblasts treated with IL-13, and AKT overexpression upregulated
      YY1, whereas blockade of AKT phosphorylation suppressed the induction of YY1 by
      IL-13 in vitro. In vivo YY1 was upregulated in fibrotic lungs from CC10-IL-13
      transgenic mice compared to that from wild-type littermates, which was associated
      with increased AKT phosphorylation. Taken together, these findings demonstrate
      that IL-13 is a potent stimulator and activator of fibroblasts, at least in part,
      through AKT-mediated YY1 activation. 

PMID- 25775217
TI  - On the Role of Proprioception in Making Free Throws in Basketball.
AB  - PURPOSE: The aim of this article was to investigate the role that proprioception
      of the upper limb plays in making basketball free throws. METHOD: We designed an
      experiment to directly correlate the performance of basketball players in a free
      throw task and an elbow- and wrist-joint position sense task. RESULTS: We found a
      moderately high correlation between the free-throw success rate and wrist-joint
      position sense and a moderate correlation between the free-throw success rate and
      elbow-joint position sense. In both cases, the most successful shooters also had
      the best proprioceptive results. CONCLUSIONS: The results indicate that free
      throw success is, at least partly, determined by players' ability to sense the
      position of the distal joints of their throwing upper limb. From a motor-control
      point of view, this suggests that basketball players may organize the
      compensatory behavior between the joints of their free-throwing arm on the basis
      of proprioception. From a practical point of view, it points toward new training
      techniques to enhance free-throwing efficiency.

PMID- 25775219
TI  - You Can't Be in Recovery If You Are on Medication: A Concept Worth Retiring.

PMID- 25775218
TI  - Hospital outcomes of extremely low birth weight infants after introduction of
      donor milk to supplement mother's milk.
AB  - AIM: This study evaluated the impact of an exclusive human milk diet to nourish
      extremely low birth weight infants in the neonatal intensive care unit. MATERIALS
      AND METHODS: This multicenter pre-post retrospective study included all inborn
      infants <1,000 g admitted to four Level IV neonatal intensive care units either
      before or after implementing a donor human milk policy. The feeding protocol was
      unchanged in both periods. Collected data included maternal/infant demographics,
      infant clinical data, and enteral intake as mother's own milk, donor milk, and
      formula. RESULTS: Two hundred one infants were enrolled. Infant growth and other
      clinical outcomes were similar in both groups. Exposure to mother's own milk at
      discharge was not different. Median time in oxygen and duration of mechanical
      ventilation were significantly higher among formula-fed infants (63 versus 192
      hours [p=0.046] and 24 versus 60 hours [p=0.016], respectively). CONCLUSIONS: Our
      results add evidence supporting the safety of donor milk. This study also found
      an association between exposure to formula in preterm infants and the requirement
      for respiratory support, a finding that warrants further investigation.

PMID- 25775220
TI  - A low molecular weight hydrogel with unusual gel aging.
AB  - We describe a dipeptide hydrogel with unusual aging characteristics. Over time, a
      transformation from a turbid gel to a transparent gel occurs which is initiated
      from the air-water interface. Here, we investigate this transition and discuss
      the implications of this aging on the bulk properties of the gel. 

PMID- 25775221
TI  - Tracer microrheology study of a hydrophobically modified comblike associative
      polymer.
AB  - The viscoelastic properties of associative polymers are important not only for
      their use as rheology modifiers but also to understand their complex structure in
      aqueous media. In this study, the dynamics of comblike hydrophobically modified
      alkali swellable associative (HASE) polymers are probed using diffusing wave
      spectroscopy (DWS) based tracer microrheology. DWS-based tracer microrheology
      accurately probes the dynamics of HASE polymers, and the extracted
      microrheological moduli versus frequency profile obtained from this technique
      closely matches that obtained from rotational rheometry measurements.
      Quantitatively, however, the moduli extracted from DWS-based tracer microrheology
      measurements are slightly higher than those obtained using rotational rheometry.
      The creep compliance, elastic modulus, and relaxation time concentration scaling
      behavior exhibits a power-law dependence. The length scale associated with the
      elastic to glassy behavior change is obtained from the time-dependent diffusion
      coefficient. The Zimm-Rouse type scaling is recovered at high frequencies but
      shows a concentration effect switching from Zimm to more Rouse-like behavior at
      higher concentrations. 

PMID- 25775223
TI  - Depressive symptoms in patients with subclinical hypothyroidism--the effect of
      treatment with levothyroxine: a double-blind randomized clinical trial.
AB  - Despite the increasing evidence for relationships between thyroid dysfunction and
      neuropsychiatric alterations, the effect of treatment of thyroid disease on
      various clinical psychiatric outcomes is controversial. The purpose of this study
      was to investigate the effect of levothyroxine treatment on depressive symptoms
      in subjects with subclinical hypothyroidism. A randomized double-blind placebo
      controlled clinical trial was performed. Sixty subjects (51 females and 9 males)
      with subclinical hypothyroidism were enrolled. Beck Depression Inventory was
      completed for all participants at the beginning of the study and 12 weeks after
      enrollment. The intervention and control groups received levothyroxine and
      placebo, respectively, for 12 weeks. There were no statistical differences in the
      total depression score and its subscales between the two groups at the beginning
      of the study. The Beck Depression Inventory score decreased from 16.79 +/- 13.25
      to 12.37 +/- 10.01 (p value = 0.04) in the intervention group. The change in
      score was not significant for the control group (13.77 +/- 11.71 to 11.86 +/-
      10.71; p value= 0.16). The affective subscale of Beck Depression Inventory did
      not change after 12 weeks of treatment with levothyroxine, while somatic subscale
      remarkably improved in the intervention group (p value = 0.02). This study showed
      the efficacy of treatment of subclinical hypothyroidism in people with
      levothyroxine in relation to depressive symptoms. 

PMID- 25775224
TI  - Relationship between Troponin Elevation, Cardiovascular History and Adverse
      Events in Patients with acute exacerbation of COPD.
AB  - Evidence suggests that troponin (Tn) elevation during acute exacerbation of
      chronic obstructive pulmonary disease (AECOPD) may predict an increase in
      mortality risk. We performed an observational study of 935 patients admitted to
      hospital for AECOPD from January 2010 to December 2012. Principal clinical and
      laboratory data were recorded, especially ischemic heart disease (IHD) history,
      Tn T values and cardiovascular drug prescription. The occurrence of all-cause
      death, cardiac death (CD), nonfatal myocardial infarction (MI), heart failure and
      cerebrovascular accident (CVA) was assessed on December 2013. Overall, 694
      patients respected inclusion and exclusion criteria. We identified 210 (30%)
      patients without Tn elevation (negative Tn T group) and 484 (70%) patients with
      Tn elevation (positive Tn T group). With the exception of CVA, all adverse events
      were significantly higher in positive Tn T group as compared to negative Tn T
      group. At multivariable analysis, positive Tn T failed to predict all-cause
      death. Contrarily, positive Tn T emerged as independent predictors of CD (HR
      1.61, 95%CI 1.2-2.2, p = 0.04), nonfatal MI (HR 3.12, 95%CI 1.4-8.1, p = 0.03)
      and composite endpoint including CD and nonfatal MI (HR 1.73, 95%CI 1.2-2.7, p =
      0.03). Of note, positive Tn T stratified prognosis in patients without IHD
      history, but not in those with IHD history. In conclusion, after hospital
      admission for AECOPD, we observed a significant increase in the risk of cardiac
      adverse events in patients with Tn T elevation, especially in those without IHD
      history.

PMID- 25775225
TI  - Changes in psychiatric symptoms among persons with methamphetamine dependence
      predicts changes in severity of drug problems but not frequency of use.
AB  - BACKGROUND: Few studies have examined how changes in psychiatric symptoms over
      time are associated with changes in drug use and severity of drug problems. No
      studies have examined these relationships among methamphetamine (MA)-dependent
      persons receiving motivational interviewing within the context of standard
      outpatient treatment. METHODS: Two hundred seventeen individuals with MA
      dependence were randomly assigned to a standard single session of motivational
      interviewing (MI) or an intensive 9-session model of MI. Both groups received
      standard outpatient group treatment. The Addiction Severity Index (ASI) and
      timeline follow-back (TLFB) for MA use were administered at treatment entry and 2
      , 4-, and 6-month follow-ups. RESULTS: Changes in ASI psychiatric severity
      between baseline and 2 months predicted changes in ASI drug severity during the
      same time period, but not changes on measures of MA use. Item analysis of the ASI
      drug scale showed that psychiatric severity predicted how troubled or bothered
      participants were by their drug us, how important they felt it was for them to
      get treatment, and the number of days they experienced drug problems. However, it
      did not predict the number days they used drugs in the past 30 days. These
      associations did not differ between study conditions, and they persisted when
      psychiatric severity and outcomes were compared across 4- and 6-month time
      periods. CONCLUSIONS: Results are among the first to track how changes in
      psychiatric severity over time are associated with changes in MA use and severity
      of drug problems. Treatment efforts targeting reduction of psychiatric symptoms
      among MA-dependent persons might be helpful in reducing the level of distress and
      problems associated with MA use but not how often it is used. There is a need for
      additional research describing the circumstances under which the experiences and
      perceptions of drug-related problems diverge from frequency of consumption.

PMID- 25775226
TI  - Race-Specific Adult-Plant Resistance in Winter Wheat to Stripe Rust and
      Characterization of Pathogen Virulence Patterns.
AB  - Stripe rust, caused by Puccinia striiformis f. sp. tritici, is an important
      disease of wheat in the Great Plains and southeastern United States. Growing
      resistant cultivars is the preferred means for managing stripe rust, but new
      virulence in the pathogen population overcomes some of the resistance. The
      objectives of this study were to characterize the stripe rust resistance in
      contemporary soft and hard red winter wheat cultivars, to characterize the
      virulence of P. striiformis f. sp. tritici isolates based on the resistances
      found in the cultivars, and to determine wheat breeders' perceptions on the
      importance and methods for achieving stripe rust resistance. Seedlings of
      cultivars were susceptible to recent isolates, indicating they lacked effective
      all-stage resistance. However, adult-plants were resistant or susceptible
      depending on the isolate, indicating they had race-specific adult-plant
      resistance. Using isolates collected from 1990 to 2013, six major virulence
      patterns were identified on adult plants of twelve cultivars that were selected
      as adult-plant differentials. Race-specific adult-plant resistance appears to be
      the only effective type of resistance protecting wheat from stripe rust in
      eastern United States. Among wheat breeders, the importance of incorporating
      stripe rust resistance into cultivars ranged from high to low depending on the
      frequency of epidemics in their region, and most sources of stripe rust
      resistance were either unknown or already overcome by virulence in the pathogen
      population. Breeders with a high priority for stripe rust resistance made most of
      their selections based on adult-plant reactions in the field, whereas breeders
      with a low priority for resistance based selections on molecular markers for
      major all-stage resistance genes. 

PMID- 25775227
TI  - Inhibitory Effects of Two Varieties of Tunisian Pomegranate (Punica granatum L.)
      Extracts on Gastrointestinal Transit in Rat.
AB  - The present study was undertaken to determine whether total and methanol juice
      extracts of two Tunisian Pomegranate (Punica granatum L.) varieties (Garsi and
      Gabsi) protect against diarrhea as well as their effects on gastrointestinal
      transit (GIT) in healthy rats. In this respect, male Wistar rats were used and
      divided into control- and pomegranate-treated groups. The antidiarrheal activity
      was evaluated using the castor oil-induced diarrhea method and the GIT was
      assessed using charcoal meal. Our results showed that total and methanol P.
      granatum juice extracts produced a significant dose-dependent protection against
      castor oil-induced diarrhea. Pomegranate extracts and juice also decreased the
      GIT significantly and dose dependently. Importantly, the Garsi variety appeared
      to be more effective than the Gabsi variety on these two parameters. These
      findings suggest that pomegranate extracts have a potent antidiarrheal property
      in rats confirming their efficiency in the Tunisian traditional medicine. 

PMID- 25775228
TI  - Tau assembly: the dominant role of PHF6 (VQIVYK) in microtubule binding region
      repeat R3.
AB  - Self-aggregation of the microtubule-binding protein Tau reduces its functionality
      and is tightly associated with Tau-related diseases, termed tauopathies. Tau
      aggregation is also strongly associated with two nucleating six-residue segments,
      namely PHF6 (VQIVYK) and PHF6* (VQIINK). In this paper, using experiments and
      computational modeling, we study the self-assembly of individual and binary
      mixtures of Tau fragments containing PHF6* (R2/wt; (273)GKVQIINKKLDL(284)) and
      PHF6 (R3/wt; (306)VQIVYKPVDLSK(317)) and a mutant R2/DeltaK280 associated with a
      neurodegenerative tauopathy. The initial stage of aggregation is probed by ion
      mobility mass spectrometry, the kinetics of aggregation monitored with Thioflavin
      T assays, and the morphology of aggregates visualized by transmission electron
      microscopy. Insights into the structure of early aggregates and the factors
      stabilizing the aggregates are obtained from replica exchange molecular dynamics
      simulations. Our data suggest that R3/wt has a much stronger aggregation
      propensity than either R2/wt or R2/DeltaK280. Heterodimers containing R3/wt are
      less stable than R3/wt homodimers but much more stable than homodimers of R2/wt
      and R2/DeltaK280, suggesting a possible role of PHF6*-PHF6 interactions in
      initiating the aggregation of full-length Tau. Lastly, R2/DeltaK280 binds more
      strongly to R3/wt than R2/wt, suggesting a possible mechanism for a pathological
      loss of normal Tau function. 

PMID- 25775229
TI  - High frequency of mononuclear myeloid-derived suppressor cells is associated with
      exacerbation of inflammatory bowel disease.
AB  - Exacerbation and relapse of inflammatory bowel disease (IBD) is associated with
      reduced antibacterial immunity and increased immune regulatory activity, but the
      source of increased immune regulation during episodes of disease activity is
      unclear. Myeloid-derived suppressor cells (MDSCs) are a cell type with a well
      recognized role in limiting immune reactions. MDSC function in IBD and its
      relation to disease activity, however, remains unexplored. Here we show that
      patients with either ulcerative colitis (UC) or Crohn's disease (CD) have high
      peripheral blood levels of mononuclear MDSCs. Especially exacerbation of disease
      is associated with higher levels of mononuclear MDSC counts compared with those
      in remission of disease. Interestingly, chronic experimental colitis in mice
      coincides with increased MDCS mobilization. Thus, our results suggest that
      mononuclear MDCS are endogenous antagonists of immune system functionality in
      mucosal inflammation and the depression of antibacterial immunity associated with
      exacerbation of disease might involve increased activity of the MDSC compartment.

PMID- 25775230
TI  - Disgust sensitivity predicts defensive responding to mortality salience.
AB  - Disgust protects the physical self. The present authors suggest that disgust also
      contributes to the protection of the psychological self by fostering stronger
      defensive reactions to existential concerns. To test this idea, 3 studies
      examined the link between disgust sensitivity and defensive responses to
      mortality salience or "terror management" processes (Greenberg, Solomon, &
      Pyszczynski, 1997). Each study included an individual difference measure of
      disgust sensitivity, a manipulation of mortality salience, and a dependent
      measure of defensive responding. In Study 1, disgust sensitivity predicted
      increases in worldview defense in the mortality salience condition but not in the
      control condition. In Study 2, disgust sensitivity predicted increases in
      optimistic perceptions of the future in the mortality salience condition but not
      in the control condition. In Study 3, disgust sensitivity predicted reductions in
      delay discounting for those in the mortality salience condition such that those
      higher in disgust sensitivity discounted the future less. This pattern did not
      occur in the control condition. These findings highlight disgust sensitivity as a
      key to understanding reactions to mortality salience, and they support the view
      that disgust-related responses protect against both physical (e.g., noxious
      substances) and psychological threats.

PMID- 25775231
TI  - Maintaining an even keel: An affect-mediated model of mindfulness and hostile
      work behavior.
AB  - Mindfulness, defined in terms of greater attention to and awareness of the
      present moment, may benefit equanimity both outside and inside the workplace. Two
      studies (total N = 224) of part-time employees supported this idea. Employees who
      were higher in dispositional mindfulness were less Machiavellian (Study 1), and
      they engaged in fewer counterproductive work behaviors (CWBs; Study 2).
      Furthermore, and consistent with an emotion-related theory of mindfulness, these
      inverse relationships were mediated by hostile feelings such as irritation and
      anger. That is, mindful people were less hostile in their behaviors in part
      because they were less prone to hostile feelings. The results suggest that
      mindfulness may be an efficacious state in reducing hostile feelings and
      behaviors at work. More generally, they contribute to an emotion-related
      perspective of mindfulness and some of its behavioral consequences.

PMID- 25775232
TI  - Trait susceptibility to worry modulates the effects of cognitive load on
      cognitive control: An ERP study.
AB  - According to the predictions of attentional control theory (ACT) of anxiety
      (Eysenck, Derakshan, Santos, & Calvo, 2007), worry is a central feature of
      anxiety that interferes with the ability to inhibit distracting information
      necessary for successful task performance. However, it is unclear how such
      cognitive control deficits are modulated by task demands and by the emotionality
      of the distractors. A sample of 31 participants (25 female) completed a novel
      flanker task with emotional and neutral distractors under low- and high-cognitive
      load conditions. The negative-going N2 event-related potential was measured to
      index participants' level of top-down resource allocation in the inhibition of
      distractors under high- and low-load conditions. Results showed N2 amplitudes
      were larger under high- compared with low-load conditions. In addition, under
      high but not low load, trait worry was associated with greater N2 amplitudes. Our
      findings support ACT predictions that trait worry adversely affects goal-directed
      behavior, and is associated with greater recruitment of cognitive resources to
      inhibit the impact of distracting information under conditions in which cognitive
      resources are taxed.

PMID- 25775233
TI  - Interactions among emotional attention, encoding, and retrieval of ambiguous
      information: An eye-tracking study.
AB  - Emotional biases in attention modulate encoding of emotional material into long
      term memory, but little is known about the role of such attentional biases during
      emotional memory retrieval. The present study investigated how emotional biases
      in memory are related to attentional allocation during retrieval. Forty-nine
      individuals encoded emotionally positive and negative meanings derived from
      ambiguous information and then searched their memory for encoded meanings in
      response to a set of retrieval cues. The remember/know/new procedure was used to
      classify memories as recollection-based or familiarity-based, and gaze behavior
      was monitored throughout the task to measure attentional allocation. We found
      that a bias in sustained attention during recollection-based, but not familiarity
      based, retrieval predicted subsequent memory bias toward positive versus negative
      material following encoding. Thus, during emotional memory retrieval, attention
      affects controlled forms of retrieval (i.e., recollection) but does not modulate
      relatively automatic, familiarity-based retrieval. These findings enhance
      understanding of how distinct components of attention regulate the emotional
      content of memories. Implications for theoretical models and emotion regulation
      are discussed.

PMID- 25775234
TI  - Study of Bone Surface Absorbed Dose in Treatment of Bone Metastases via Selected
      Radiopharmaceuticals: Using MCNP4C Code and Available Experimental Data.
AB  - Bone metastases are major clinical concern that can cause severe problems for
      patients. Currently, various beta emitters are used for bone pain palliation.
      This study, describes the process for absorbed dose prediction of selected bone
      surface and volume-seeking beta emitter radiopharmaceuticals such as (32)P,
      (89)SrCl2,(90)Y-EDTMP,(153)Sm-EDTMP, (166)Ho-DOTMP, (177)Lu-EDTMP,(186)Re-HEDP,
      and (188)Re-HEDP in human bone, using MCNP code. Three coaxial sub-cylinders 5 cm
      in height and 1.2, 2.6, and 7.6 cm in diameter were used for bone marrow, bone,
      and muscle simulation respectively. The *F8 tally was employed to calculate
      absorbed dose in the MCNP4C simulations. Results show that with injection of 1
      MBq of these radiopharmaceuticals given to a 70 kg adult man, (32)P, (89)SrCl2,
      and (90)Y-EDTMP radiopharmaceuticals will have the highest amount of bone surface
      absorbed dose, where beta particles will have the greatest proportion in absorbed
      dose of bone surface in comparison with gamma radiation. These results
      demonstrate moderate agreement with available experimental data. 

PMID- 25775236
TI  - Xenosurveillance: a novel mosquito-based approach for examining the human
      pathogen landscape.
AB  - BACKGROUND: Globally, regions at the highest risk for emerging infectious
      diseases are often the ones with the fewest resources. As a result, implementing
      sustainable infectious disease surveillance systems in these regions is
      challenging. The cost of these programs and difficulties associated with
      collecting, storing and transporting relevant samples have hindered them in the
      regions where they are most needed. Therefore, we tested the sensitivity and
      feasibility of a novel surveillance technique called xenosurveillance. This
      approach utilizes the host feeding preferences and behaviors of Anopheles
      gambiae, which are highly anthropophilic and rest indoors after feeding, to
      sample viruses in human beings. We hypothesized that mosquito bloodmeals could be
      used to detect vertebrate viral pathogens within realistic field collection
      timeframes and clinically relevant concentrations. METHODOLOGY/PRINCIPAL
      FINDINGS: To validate this approach, we examined variables influencing virus
      detection such as the duration between mosquito blood feeding and mosquito
      processing, the pathogen nucleic acid stability in the mosquito gut and the
      pathogen load present in the host's blood at the time of bloodmeal ingestion
      using our laboratory model. Our findings revealed that viral nucleic acids, at
      clinically relevant concentrations, could be detected from engorged mosquitoes
      for up to 24 hours post feeding by qRT-PCR. Subsequently, we tested this approach
      in the field by examining blood from engorged mosquitoes from two field sites in
      Liberia. Using next-generation sequencing and PCR we were able to detect the
      genetic signatures of multiple viral pathogens including Epstein-Barr virus and
      canine distemper virus. CONCLUSIONS/SIGNIFICANCE: Together, these data
      demonstrate the feasibility of xenosurveillance and in doing so validated a
      simple and non-invasive surveillance tool that could be used to complement
      current biosurveillance efforts.

PMID- 25775235
TI  - Heterogeneous photochemistry in the atmosphere.

PMID- 25775237
TI  - Same same but different. Different trigeminal chemoreceptors share the same
      central pathway.
AB  - Intranasal trigeminal sensations are important in everyday life of human beings,
      as they play a governing role in protecting the airways from harm. Trigeminal
      sensations arise from the binding of a ligand to various sub-types of transient
      receptor potential (TRP) channels located on mucosal branches of the trigeminal
      nerve. Which underlying neural networks are involved in the processing of various
      trigeminal inputs is still unknown. To target this unresolved question fourteen
      healthy human subjects were investigated by completing three functional magnetic
      resonance imaging (fMRI) scanning sessions during which three trigeminal
      substances, activating varying sub-types of chemoreceptors and evoking different
      sensations in the nose were presented: CO2, menthol and cinnamaldehyde. We
      identified similar functional networks responding to all stimuli: an olfactory
      network, a somatosensory network and an integrative network. The processing
      pathway of all three stimulants was represented by the same functional networks,
      although CO2 evokes painful but virtually odorless sensations, and the two other
      stimulants, menthol and cinnamaldehyde are perceived as mostly non painful with a
      clear olfactory percept. Therefore, our results suggest a common central
      processing pathway for trigeminal information regardless of the trigeminal
      chemoreceptor and sensation type. 

PMID- 25775238
TI  - Multiple proteases to localize oxidation sites.
AB  - Proteins present in cellular environments with high levels of reactive oxygen and
      nitrogen species and/or low levels of antioxidants are highly susceptible to
      oxidative post-translational modification (PTM). Irreversible oxidative PTMs can
      generate a complex distribution of modified protein molecules, recently termed as
      proteoforms. Using ubiquitin as a model system, we mapped oxidative modification
      sites using trypsin, Lys-C, and Glu-C peptides. Several M+16 Da proteoforms were
      detected as well as proteoforms that include other previously unidentified
      oxidative modifications. This work highlights the use of multiple protease
      digestions to give insights to the complexity of oxidative modifications possible
      in bottom-up analyses. 

PMID- 25775240
TI  - Correction: predicting in vitro rumen VFA production using CNCPS carbohydrate
      fractions with multiple linear models and artificial neural networks.

PMID- 25775239
TI  - Layered hybrid perovskites with micropores created by alkylammonium functional
      silsesquioxane interlayers.
AB  - Layered organic-inorganic hybrid perovskites that consist of metal halides and
      organic interlayers are a class of low-dimensional materials. Here, we report the
      fabrication of layered hybrid perovskites using metal halides and silsesquioxane
      with a cage-like structure. We used a silsesquioxane as an interlayer to produce
      a rigid structure and improve the functionality of perovskite layers.
      Propylammonium-functionalized silsesquioxane and metal halide salts (CuCl2,
      PdCl2, PbCl2, and MnCl2) were self-assembled to form rigid layered perovskite
      structures with high crystallinity. The rigid silsesquioxane structure produces
      micropores between the perovskite layers that can potentially be filled with
      different molecules to tune the dielectric constants of the interlayers. The
      obtained silsesquioxane-metal halide hybrid perovskites exhibit some
      characteristic properties of layered perovskites including magnetic ordering
      (CuCl4(2-) and MnCl4(2-)) and excitonic absorption/emission (PbCl4(2-)). Our
      results indicate that inserting silsesquioxane interlayers into hybrid
      perovskites retains and enhances the low-dimensional properties of the materials.

PMID- 25775241
TI  - Optical imaging of targeted beta-galactosidase in brain tumors to detect EGFR
      levels.
AB  - A current limitation in molecular imaging is that it often requires genetic
      manipulation of cancer cells for noninvasive imaging. Other methods to detect
      tumor cells in vivo using exogenously delivered and functionally active
      reporters, such as beta-gal, are required. We report the development of a
      platform system for linking beta-gal to any number of different ligands or
      antibodies for in vivo targeting to tissue or cells, without the requirement for
      genetic engineering of the target cells prior to imaging. Our studies demonstrate
      significant uptake in vitro and in vivo of an EGFR-targeted beta-gal complex. We
      were then able to image orthotopic brain tumor accumulation and localization of
      the targeted enzyme when a fluorophore was added to the complex, as well as
      validate the internalization of the intravenously administered beta-gal reporter
      complex ex vivo. After fluorescence imaging localized the beta-gal complexes to
      the brain tumor, we topically applied a bioluminescent beta-gal substrate to
      serial sections of the brain to evaluate the delivery and integrity of the
      enzyme. Finally, robust bioluminescence of the EGFR-targeted beta-gal complex was
      captured within the tumor during noninvasive in vivo imaging. 

PMID- 25775242
TI  - Soluble ligands for the NKG2D receptor are released during endometriosis and
      correlate with disease severity.
AB  - BACKGROUND: Endometriosis is a benign gynaecological disease. Abundant bulk of
      evidence suggests that patients with endometriosis have an immunity dysfunction
      that enables ectopic endometrial cells to implant and proliferate. Previous
      studies show that natural killer cells have a pivotal role in the immune control
      of endometriosis. METHODS AND FINDINGS: This is a prospective laboratory study
      conducted in a tertiary-care university hospital between January 2011 and April
      2013. We investigated non-pregnant, younger than 42-year-old patients (n= 202)
      during surgery for benign gynaecological conditions. After complete surgical
      exploration of the abdominopelvic cavity, 121 women with histologically proven
      endometriosis and 81 endometriosis-free controls women were enrolled. Patients
      with endometriosis were classified according to a surgical classification in
      three different types of endometriosis: superficial peritoneal endometriosis
      (SUP), ovarian endometrioma (OMA) and deep infiltrating endometriosis (DIE).
      Peritoneal fluid samples were obtained from all study participants during the
      surgery in order to detect soluble NKG2D ligands (MICA, MICB and ULBP-2). When
      samples with undetectable peritoneal fluid levels of MICA, MICB and ULBP-2 were
      excluded, MICA ratio levels were significantly higher in endometriosis patients
      than in controls (median, 1.1 pg/mg; range, 0.1-143.5 versus median, 0.6 pg/mg;
      range, 0.1-3.5; p=0.003). In a similar manner peritoneal fluid MICB levels were
      also increased in endometriosis-affected patients compared with disease-free
      women (median, 4.6 pg/mg; range, 1.2-4702 versus median, 3.4 pg/mg; range, 0.7
      20.1; p=0.001). According to the surgical classification, peritoneal fluid
      soluble MICA, MICB and ULBP-2 ratio levels were significantly increased in DIE as
      compared to controls (p=0.015, p=0.003 and p=0.045 respectively). MICA ratio
      levels also correlated with dysmenorrhea (r=0.232; p=0.029), total rAFS score
      (r=0.221; p=0.031) and adhesions rAFS score (r=0.221; p=0.031). CONCLUSIONS: We
      demonstrate a significant increase of peritoneal fluid NKG2D ligands in women
      with endometriosis especially in those cases presenting DIE. This study suggests
      that NKG2D ligands shedding is a novel pathway in endometriosis complex
      pathogenesis that impairs NK cell function.

PMID- 25775243
TI  - Multivariate statistical assessment of predictors of firefighters' muscular and
      aerobic work capacity.
AB  - Physical capacity has previously been deemed important for firefighters physical
      work capacity, and aerobic fitness, muscular strength, and muscular endurance are
      the most frequently investigated parameters of importance. Traditionally,
      bivariate and multivariate linear regression statistics have been used to study
      relationships between physical capacities and work capacities among firefighters.
      An alternative way to handle datasets consisting of numerous correlated variables
      is to use multivariate projection analyses, such as Orthogonal Projection to
      Latent Structures. The first aim of the present study was to evaluate the
      prediction and predictive power of field and laboratory tests, respectively, on
      firefighters' physical work capacity on selected work tasks. Also, to study if
      valid predictions could be achieved without anthropometric data. The second aim
      was to externally validate selected models. The third aim was to validate
      selected models on firefighters' and on civilians'. A total of 38 (26 men and 12
      women) + 90 (38 men and 52 women) subjects were included in the models and the
      external validation, respectively. The best prediction (R2) and predictive power
      (Q2) of Stairs, Pulling, Demolition, Terrain, and Rescue work capacities included
      field tests (R2 = 0.73 to 0.84, Q2 = 0.68 to 0.82). The best external validation
      was for Stairs work capacity (R2 = 0.80) and worst for Demolition work capacity
      (R2 = 0.40). In conclusion, field and laboratory tests could equally well predict
      physical work capacities for firefighting work tasks, and models excluding
      anthropometric data were valid. The predictive power was satisfactory for all
      included work tasks except Demolition. 

PMID- 25775244
TI  - Reduced chemical warfare agent sorption in polyurethane-painted surfaces via
      plasma-enhanced chemical vapor deposition of perfluoroalkanes.
AB  - Perfluoralkalation via plasma chemical vapor deposition has been used to improve
      hydrophobicity of surfaces. We have investigated this technique to improve the
      resistance of commercial polyurethane coatings to chemicals, such as chemical
      warfare agents. The reported results indicate the surface treatment minimizes the
      spread of agent droplets and the sorption of agent into the coating. The
      improvement in resistance is likely due to reduction of the coating's surface
      free energy via fluorine incorporation, but may also have contributing effects
      from surface morphology changes. The data indicates that plasma-based surface
      modifications may have utility in improving chemical resistance of commercial
      coatings. 

PMID- 25775245
TI  - Inferring landscape-scale land-use impacts on rivers using data from mesocosm
      experiments and artificial neural networks.
AB  - Identifying land-use drivers of changes in river condition is complicated by
      spatial scale, geomorphological context, land management, and correlations among
      responding variables such as nutrients and sediments. Furthermore, variations in
      standard metrics, such as substratum composition, do not necessarily relate
      causally to ecological impacts. Consequently, the absence of a significant
      relationship between a hypothesised driver and a dependent variable does not
      necessarily indicate the absence of a causal relationship. We conducted a
      gradient survey to identify impacts of catchment-scale grazing by domestic
      livestock on river macroinvertebrate communities. A standard correlative approach
      showed that community structure was strongly related to the upstream catchment
      area under grazing. We then used data from a stream mesocosm experiment that
      independently quantified the impacts of nutrients and fine sediments on
      macroinvertebrate communities to train artificial neural networks (ANNs) to
      assess the relative influence of nutrients and fine sediments on the survey sites
      from their community composition. The ANNs developed to predict nutrient impacts
      did not find a relationship between nutrients and catchment area under grazing,
      suggesting that nutrients were not an important factor mediating grazing impacts
      on community composition, or that these ANNs had no generality or insufficient
      power at the landscape-scale. In contrast, ANNs trained to predict the impacts of
      fine sediments indicated a significant relationship between fine sediments and
      catchment area under grazing. Macroinvertebrate communities at sites with a high
      proportion of land under grazing were thus more similar to those resulting from
      high fine sediments in a mesocosm experiment than to those resulting from high
      nutrients. Our study confirms that 1) fine sediment is an important mediator of
      land-use impacts on river macroinvertebrate communities, 2) ANNs can successfully
      identify subtle effects and separate the effects of correlated variables, and 3)
      data from small-scale experiments can generate relationships that help explain
      landscape-scale patterns. 

PMID- 25775246
TI  - Large cohort screening of G6PD deficiency and the mutational spectrum in the
      Dongguan District in Southern China.
AB  - BACKGROUND: Glucose-6-phosphate dehydrogenase (G6PD) deficiency is a common
      enzymatic disorder of the erythrocytes that affects 400 million people worldwide.
      We developed a PCR-reverse dot blot (RDB) assay to screen twenty genotypes of
      seventeen Chinese G6PD mutations and investigate the spectrum of G6PD deficiency
      mutations in Dongguan District, Guangdong Province, in southern China. METHOD:
      The PCR-RDB assay consists of multiplex PCR amplification of seven fragments in
      the G6PD target sequence of wild-type and mutant genomic DNA samples followed by
      hybridization to a test strip containing allele-specific oligonucleotide probes.
      A total of 16,464 individuals were analyzed by a combination of phenotypic
      screening and genotypic detection using the PCR-RDB assay and DNA sequence
      analysis. RESULTS: The PCR-RDB assay had a detection rate of 98.1%, which was
      validated by direct sequencing in a blind study with 100% concordance. The G6PD
      deficiency incidence rate in Dongguan District is 4.08%. Thirty-two genotypes
      from 469 individuals were found. The two most common variants were c.1376G>T and
      c.1388G>A, followed by c.95A>G, c.871G>A, c.392G>T, and c.1024 C>T. In addition,
      two rare mutations (c.703C>A and c.406C>T) were detected by DNA sequencing
      analysis. In our study, 65 cases harbored the C1311T/IVS polymorphism and 67
      cases were homozygote. CONCLUSION: The PCR-RDB assay we established is a reliable
      and effective method for screening G6PD mutations in the Chinese population. Data
      on the spectrum of mutations in the Dongguan District is beneficial to the
      clinical diagnosis and prevention of G6PD deficiency.

PMID- 25775247
TI  - The 1.7 A X-ray crystal structure of the porcine factor VIII C2 domain and
      binding analysis to anti-human C2 domain antibodies and phospholipid surfaces.
AB  - The factor VIII C2 domain is essential for binding to activated platelet surfaces
      as well as the cofactor activity of factor VIII in blood coagulation. Inhibitory
      antibodies against the C2 domain commonly develop following factor VIII
      replacement therapy for hemophilia A patients, or they may spontaneously arise in
      cases of acquired hemophilia. Porcine factor VIII is an effective therapeutic for
      hemophilia patients with inhibitor due to its low cross-reactivity; however, the
      molecular basis for this behavior is poorly understood. In this study, the X-ray
      crystal structure of the porcine factor VIII C2 domain was determined, and
      superposition of the human and porcine C2 domains demonstrates that most surface
      exposed differences cluster on the face harboring the "non-classical" antibody
      epitopes. Furthermore, antibody-binding results illustrate that the "classical"
      3E6 antibody can bind both the human and porcine C2 domains, although the
      inhibitory titer to human factor VIII is 41 Bethesda Units (BU)/mg IgG versus 0.8
      BU/mg IgG to porcine factor VIII, while the non-classical G99 antibody does not
      bind to the porcine C2 domain nor inhibit porcine factor VIII activity. Further
      structural analysis of differences between the electrostatic surface potentials
      suggest that the C2 domain binds to the negatively charged phospholipid surfaces
      of activated platelets primarily through the 3E6 epitope region. In contrast, the
      G99 face, which contains residue 2227, should be distal to the membrane surface.
      Phospholipid binding assays indicate that both porcine and human factor VIII C2
      domains bind with comparable affinities, and the human K2227A and K2227E mutants
      bind to phospholipid surfaces with similar affinities as well. Lastly, the G99
      IgG bound to PS-immobilized factor VIII C2 domain with an apparent dissociation
      constant of 15.5 nM, whereas 3E6 antibody binding to PS-bound C2 domain was not
      observed. 

PMID- 25775248
TI  - Intrinsic motivations drive learning of eye movements: an experiment with human
      adults.
AB  - Intrinsic motivations drive the acquisition of knowledge and skills on the basis
      of novel or surprising stimuli or the pleasure to learn new skills. In so doing,
      they are different from extrinsic motivations that are mainly linked to drives
      that promote survival and reproduction. Intrinsic motivations have been
      implicitly exploited in several psychological experiments but, due to the lack of
      proper paradigms, they are rarely a direct subject of investigation. This article
      investigates how different intrinsic motivation mechanisms can support the
      learning of visual skills, such as "foveate a particular object in space", using
      a gaze contingency paradigm. In the experiment participants could freely foveate
      objects shown in a computer screen. Foveating each of two "button" pictures
      caused different effects: one caused the appearance of a simple image (blue
      rectangle) in unexpected positions, while the other evoked the appearance of an
      always-novel picture (objects or animals). The experiment studied how two
      possible intrinsic motivation mechanisms might guide learning to foveate one or
      the other button picture. One mechanism is based on the sudden, surprising
      appearance of a familiar image at unpredicted locations, and a second one is
      based on the content novelty of the images. The results show the comparative
      effectiveness of the mechanism based on image novelty, whereas they do not
      support the operation of the mechanism based on the surprising location of the
      image appearance. Interestingly, these results were also obtained with
      participants that, according to a post experiment questionnaire, had not
      understood the functions of the different buttons suggesting that novelty-based
      intrinsic motivation mechanisms might operate even at an unconscious level. 

PMID- 25775249
TI  - Accelerometer-derived sedentary and physical activity time in overweight/obese
      adults with type 2 diabetes: cross-sectional associations with cardiometabolic
      biomarkers.
AB  - OBJECTIVE: To examine the associations of sedentary time and physical activity
      with biomarkers of cardiometabolic health, including the potential collective
      impact of shifting mean time use from less- to more-active behaviours (cross
      sectionally, using isotemporal substitution), in adults with type 2 diabetes.
      METHODS: Participants with overweight/obese body mass index (BMI; >=25 kg/m2) (n
      = 279; 158 men, mean [SD] age = 58.2 [8.6] years) wore Actigraph GT1M
      accelerometers (waking hours; seven days) to assess moderate- to vigorous
      intensity physical activity (MVPA), light-intensity activity, and sedentary time
      (segregated into non-prolonged [accumulated in bouts <30min] and prolonged
      [accumulated in bouts >=30 min]). Cross-sectional associations with waist
      circumference, BMI, fasting blood (HbA1c, glucose, triacylglycerols, high-density
      lipoprotein cholesterol), and blood pressure of these activity variables (30
      min/day increments) were examined adjusted for confounders and wear then, if
      significant, examined using isotemporal substitution modelling. RESULTS: Waist
      circumference and BMI were significantly (p<0.05) associated with more prolonged
      sedentary time and less light-intensity activity. Light intensity activity was
      also significantly associated with lower fasting plasma glucose (relative rate:
      0.98, 95% CI: 0.97, 1.00; p<0.05). No biomarker was significantly associated with
      non-prolonged sedentary time or MVPA. Lower mean prolonged sedentary time (-30
      min/day) with higher mean light intensity time (+30 min/day) was significantly
      associated with lower waist circumference (beta = -0.77, 95% CI: -1.33, -0.22
      cm). Lower mean prolonged sedentary time (-30 min/day) with either 30 min/day
      higher mean non-prolonged sedentary time (beta = -0.35, 95%CI: -0.70, -0.01
      kg/m2) or light-intensity time (beta = -0.36, -0.61, -0.11 kg/m2) was associated
      with significantly lower average BMI. CONCLUSIONS: Significantly improved mean
      levels of waist circumference and BMI were observed when shifting time from
      prolonged sedentary to non-prolonged sedentary or light-intensity activity (cross
      sectionally). Lifestyle interventions in overweight/obese adults with type 2
      diabetes might consider targeting shifts in these non-MVPA activities to more
      rigorously evaluate their potential cardiometabolic benefit in this population.

PMID- 25775250
TI  - The use of genus-specific amplicon pyrosequencing to assess phytophthora species
      diversity using eDNA from soil and water in Northern Spain.
AB  - Phytophthora is one of the most important and aggressive plant pathogenic genera
      in agriculture and forestry. Early detection and identification of its pathways
      of infection and spread are of high importance to minimize the threat they pose
      to natural ecosystems. eDNA was extracted from soil and water from forests and
      plantations in the north of Spain. Phytophthora-specific primers were adapted for
      use in high-throughput Sequencing (HTS). Primers were tested in a control
      reaction containing eight Phytophthora species and applied to water and soil eDNA
      samples from northern Spain. Different score coverage threshold values were
      tested for optimal Phytophthora species separation in a custom-curated database
      and in the control reaction. Clustering at 99% was the optimal criteria to
      separate most of the Phytophthora species. Multiple Molecular Operational
      Taxonomic Units (MOTUs) corresponding to 36 distinct Phytophthora species were
      amplified in the environmental samples. Pyrosequencing of amplicons from soil
      samples revealed low Phytophthora diversity (13 species) in comparison with the
      35 species detected in water samples. Thirteen of the MOTUs detected in rivers
      and streams showed no close match to sequences in international sequence
      databases, revealing that eDNA pyrosequencing is a useful strategy to assess
      Phytophthora species diversity in natural ecosystems. 

PMID- 25775251
TI  - The ophthalmic branch of the Gutenberg Health Study: study design, cohort profile
      and self-reported diseases.
AB  - PURPOSE: This paper describes the study design, methodology, cohort profile and
      self-reported diseases in the ophthalmological branch of the Gutenberg Health
      Study (GHS). METHODS: The GHS is an ongoing, prospective, interdisciplinary,
      single-center, population-based cohort study in Germany. The main goals of the
      ophthalmological section are to assess the prevalence and incidence of ocular
      diseases and to explore risk factors, genetic determinants and associations with
      systemic diseases and conditions. The eye examination at baseline included a
      medical history, self-reported eye diseases, visual acuity, refractive errors,
      intraocular pressure, visual field, pachymetry, keratometry, fundus photography
      and tear sampling. The 5-year follow-up visit additionally encompassed optical
      coherence tomography, anterior segment imaging and optical biometry. The general
      examination included anthropometry; blood pressure measurement; carotid artery
      ultrasound; electrocardiogram; echocardiography; spirometry; cognitive tests;
      questionnaires; assessment of mental conditions; and DNA, RNA, blood and urine
      sampling. RESULTS: Of 15,010 participants (aged 35-74 years at the time of
      inclusion), ocular data are available for 14,700 subjects (97.9%). The mean
      visual acuity (standard deviation), mean spherical equivalent, median decimal
      visual acuity, and mean intraocular pressure were 0.08 (0.17) logMar, -0.42
      (2.43) diopters, 0.9 and 14.24 (2.79) mm Hg, respectively. The frequencies of
      self-reported strabismus, glaucoma, surgery for retinal detachment and retinal
      vascular occlusions were 2.7%, 2.3%, 0.2% and 0.4%, respectively. CONCLUSIONS:
      The GHS is the most extensive dataset of ophthalmic diseases and conditions and
      their risk factors in Germany and one of the largest cohorts worldwide. This
      dataset will provide new insight in the epidemiology of ophthalmic diseases and
      related medical specialties.

PMID- 25775252
TI  - Diabetes and chocolate: friend or foe?
AB  - Polyphenols and other compounds found in cocoa and chocolate have therapeutic
      potential in the management of diabetes in humans. Polyphenol benefits have been
      proposed supported by in vitro studies, animal work, and clinical trials, which
      have been conducted mostly in healthy volunteers. The energy-dense formulations
      of many cocoa and chocolate products, which can be up to 50% sugar by weight,
      have given the perception that chocolate may be harmful through its contribution
      to obesity. A review of both clinical trial databases and published literature
      yielded 15 registered trials and 7 published studies. The published data
      interventions reported are diverse and vary widely in quality, including poor
      selection of control products or inadequate blinding procedures. There are also
      inconsistencies in reporting of data with limited information on the effect of
      cocoa and chocolate supplementation on weight and glycemic control despite the
      potential benefits reported with respect to the cardiovascular risk factors of
      endothelial function and lipids. More studies are required powered for primary
      clinical outcomes together with the development of standardized product
      formulations that optimize the dose of polyphenols within a palatable and energy
      restricted product. 

PMID- 25775253
TI  - Bond dissociation energies of C10 and C18 methyl esters from local multireference
      averaged-coupled pair functional theory.
AB  - We previously developed a fast, local, reduced scaling Cholesky-decomposed
      multireference averaged-coupled pair functional (CD-LMRACPF2) method, which takes
      advantage of the locality of dynamic correlation and numerical approximations
      such as Cholesky decomposition and integral screening. Motivated by the desire to
      study large biodiesel methyl ester molecules, here we validate CD-LMRACPF2 for
      the computation of bond dissociation energies (BDEs) in a suite of oxygenated
      molecules, and show that the low-cost method is very accurate compared to the
      conventional variant. We then demonstrate the power of CD-LMRACPF2 for fast and
      accurate computation of energies of molecules containing up to 13 second-row
      atoms within a polarized triple-zeta (cc-pVTZ) basis set. We use biodiesel methyl
      esters as a chemically interesting model system and furnish BDEs of C10 and C18
      methyl esters, with the latter performed within a cc-pVDZ basis set. We describe
      trends in the BDEs and explain how structural (isomeric) differences affect BDEs,
      as well as discuss implications of BDE trends for biodiesel physical and chemical
      properties. 

PMID- 25775255
TI  - Cultural identity and internationally adopted children: qualitative approach to
      parental representations.
AB  - Approximately 30 000 children are adopted across national borders each year. A
      review of the literature on the cultural belonging of these internationally
      adopted children shows substantial differences between the literature from
      English-speaking countries and that from France and Europe in general. The
      objective of this study is to start from the discourse of French adoptive parents
      to explore their representations of their child's cultural belonging and their
      positions (their thoughts and representations) concerning connections with the
      child's country of birth and its culture. The study includes 51 French parents
      who adopted one or more children internationally. Each parent participated in a
      semi-structured interview, focused on the adoption procedure and their current
      associations with the child's birth country. The interviews were analyzed
      according to a qualitative phenomenological method, Interpretative
      Phenomenological Analysis. The principal themes that emerged from our analysis of
      the interviews made it possible to classify the parents into three different
      groups. The first group maintained no association with the child's country of
      birth and refused any multiplicity of cultural identities. The second group
      actively maintained regular associations with the child's country of birth and
      culture and affirmed that their family was multicultural. Finally, the third
      group adapted their associations with the child's birth country and its culture
      according to the child's questions and interests. Exploring parental
      representations of the adopted child enables professionals involved in adoption
      to provide better support to these families and to do preventive work at the
      level of family interactions. 

PMID- 25775254
TI  - Endothelin A receptor antagonist, atrasentan, attenuates renal and cardiac
      dysfunction in Dahl salt-hypertensive rats in a blood pressure independent
      manner.
AB  - Proteinuria is a hallmark of chronic kidney disease (CKD) and cardiovascular
      disease (CVD), and a good predictor of clinical outcome. Selective endothelin A
      (ETA) receptor antagonist used with renin-angiotensin system (RAS) inhibitors
      prevents development of proteinuria in CKD. However, whether the improvement in
      proteinuria would have beneficial effects on CVD, independent of RAS inhibition,
      is not well understood. In this study, we investigated whether atrasentan, an ETA
      receptor antagonist, has renal and cardiovascular effects independent of RAS
      inhibition. Male Dahl salt sensitive (DSS) rats, at six weeks of age, received
      water with or without different doses of atrasentan and/or enalapril under high
      salt (HS) diet or normal diet (ND) for 6 weeks. At the end of 12th week,
      atrasentan at a moderate dose significantly attenuated proteinuria and serum
      creatinine without reducing mean arterial pressure (MAP), thereby preventing
      cardiac hypertrophy and improving cardiac function. ACE inhibitor enalapril at a
      dose that did not significantly lowered BP, attenuated cardiac hypertrophy while
      moderately improving cardiac function without reducing proteinuria and serum
      creatinine level. Nonetheless, combined therapy of atrasentan and enalapril that
      does not altering BP exerted additional cardioprotective effect. Based on these
      findings, we conclude that BP independent monotherapy of ETA receptor antagonist
      attenuates the progression of CKD and significantly mitigates CVD independent of
      RAS inhibition. 

PMID- 25775256
TI  - High-density genetic linkage mapping in turbot (Scophthalmus maximus L.) based on
      SNP markers and major sex- and growth-related regions detection.
AB  - This paper describes the development of a high density consensus genetic linkage
      map of a turbot (Scophthalmus maximus L.) family composed of 149 mapping
      individuals using Single Nucleotide Polymorphisms (SNP) developed using the
      restriction-site associated DNA (RAD) sequencing technique with the restriction
      enzyme, PstI. A total of 6,647 SNPs were assigned to 22 linkage groups, which is
      equal to the number of chromosome pairs in turbot. For the first time, the
      average marker interval reached 0.3958 cM, which is equal to approximately 0.1203
      Mb of the turbot genome. The observed 99.34% genome coverage indicates that the
      linkage map was genome-wide. A total of 220 Quantitative Traits Locus (QTLs)
      associated with two body length traits, two body weight traits in different
      growth periods and sex determination were detected with an LOD > 5.0 in 12
      linkage groups (LGs), which explained the corresponding phenotypic variance (R2),
      ranging from 14.4-100%. Among them, 175 overlapped with linked SNPs, and the
      remaining 45 were located in regions between contiguous SNPs. According to the
      QTLs related to growth trait distribution and the changing of LGs during
      different growth periods, the growth traits are likely controlled by multi-SNPs
      distributed on several LGs; the effect of these SNPs changed during different
      growth periods. Most sex-related QTLs were detected at LG 21 with a linkage span
      of 70.882 cM. Additionally, a small number of QTLs with high feasibility and a
      narrow R2 distribution were also observed on LG7 and LG14, suggesting that multi
      LGs or chromosomes might be involved in sex determination. High homology was
      recorded between LG21 in Cynoglossus semilaevis and turbot. This high-saturated
      turbot RAD-Seq linkage map is undoubtedly a promising platform for marker
      assisted selection (MAS) and flatfish genomics research. 

PMID- 25775257
TI  - Evolution of supersaturation of amorphous pharmaceuticals: nonlinear rate of
      supersaturation generation regulated by matrix diffusion.
AB  - The importance of rate of supersaturation generation on the kinetic solubility
      profiles of amorphous systems has recently been shown by us; however, the
      previous focus was limited to constant rates of supersaturation generation. The
      objective of the current study is to further examine the effect of nonlinear rate
      profiles of supersaturation generation in amorphous systems, including (1)
      instantaneous or infinite rate (i.e., initial degree of supersaturation), (2)
      first-order rate (e.g., from dissolution of amorphous drug particles), and (3)
      matrix diffusion regulated rate (e.g., drug release from amorphous solid
      dispersions (ASDs) based on cross-linked poly(2-hydroxyethyl methacrylate)
      (PHEMA) hydrogels), on the kinetic solubility profiles of a model poorly soluble
      drug indomethacin (IND) under nonsink dissolution conditions. The previously
      established mechanistic model taking into consideration both the crystal growth
      and ripening processes was extended to predict the evolution of supersaturation
      resulting from nonlinear rates of supersaturation generation. Our results confirm
      that excessively high initial supersaturation or a rapid supersaturation
      generation leads to a surge in maximum supersaturation followed by a rapid
      decrease in drug concentration owing to supersaturation-induced precipitation;
      however, an exceedingly low degree of supersaturation or a slow rate of
      supersaturation generation does not sufficiently raise the supersaturation level,
      which results in a lower but broader maximum kinetic solubility profile. Our
      experimental data suggest that an optimal area-under-the-curve of the kinetic
      solubility profiles exists at an intermediate initial supersaturation level for
      the amorphous systems studied here, which agrees well with the predicted trend.
      Our model predictions also support our experimental findings that IND ASD in
      cross-linked PHEMA exhibits a unique kinetic solubility profile because the
      resulting supersaturation level is governed by a matrix diffusion regulated
      mechanism opposite to that resulted from a high level of initial supersaturation
      or a rapid dissolution of amorphous solids. This more gradual drug release from
      IND-PHEMA ASD leads to a more gradual buildup of a sustained supersaturation even
      without the presence of any dissolved polymer to inhibit the drug precipitation,
      which avoids the rapid surge of supersaturation above a critical value as
      normally associated with high initial degrees of supersaturation or rapid
      dissolution of amorphous IND solids and thus avoids the onset of fast
      uncontrolled precipitation. This characteristic feature makes cross-linked
      insoluble PHEMA an attractive carrier for amorphous pharmaceuticals. 

PMID- 25775258
TI  - Women favour dyadic relationships, but men prefer clubs: cross-cultural evidence
      from social networking.
AB  - The ability to create lasting, trust-based friendships makes it possible for
      humans to form large and coherent groups. The recent literature on the evolution
      of sociality and on the network dynamics of human societies suggests that large
      human groups have a layered structure generated by emotionally supported social
      relationships. There are also gender differences in adult social style which may
      involve different trade-offs between the quantity and quality of friendships.
      Although many have suggested that females tend to focus on intimate relations
      with a few other females, while males build larger, more hierarchical coalitions,
      the existence of such gender differences is disputed and data from adults is
      scarce. Here, we present cross-cultural evidence for gender differences in the
      preference for close friendships. We use a sample of ~112,000 profile pictures
      from nine world regions posted on a popular social networking site to show that,
      in self-selected displays of social relationships, women favour dyadic relations,
      whereas men favour larger, all-male cliques. These apparently different solutions
      to quality-quantity trade-offs suggest a universal and fundamental difference in
      the function of close friendships for the two sexes. 

PMID- 25775259
TI  - Immediate Impact of Hurricane Sandy on People Who Inject Drugs in New York City.
AB  - Over the eight months following Hurricane Sandy, of October 2012, we interviewed
      300 people who inject drugs in New York City. During the week after the storm,
      28% rescued others or volunteered with aid groups; 60% experienced withdrawal;
      27% shared drug injection or preparation equipment, or injected with people they
      normally would not inject with; 70% of those on opioid maintenance therapy could
      not obtain sufficient doses; and 43% of HIV-positive participants missed HIV
      medication doses. Although relatively brief, a hurricane can be viewed as a Big
      Event that can alter drug environments and behaviors, and may have lasting
      impact. The study's limitations are noted and future needed research is
      suggested. 

PMID- 25775260
TI  - Intestinal microbiota succession and immunomodulatory consequences after
      introduction of Lactobacillus reuteri I5007 in neonatal piglets.
AB  - Seventy-two, suckling piglets, obtained from 9 litters standardized to 8 piglets,
      were assigned to 1 of 3 treatments (n = 24) to compare short-term, early
      administration with intermittent, longer-term administration of Lactobacillus
      reuteri I5007. The treatments were a control (given a placebo of 0.1% peptone
      water from day 1 to 5) or treatments in which 1.7 * 1010 CFU L. reuteri was
      administrated either daily for 4 days starting on day 1 or every 4th day from day
      1 to 17. Five piglets per treatment were killed at 3 time points (day 7, 14 and
      21). Denaturing Gradient Electrophoresis of ileal digesta revealed an increase in
      the presence of L. reuteri I5007 and Clostridium lentocellum (on day 14 and 21)
      in the every 4th-day treatment and Actinobacillus porcinus (on day 7 and 14) in
      both L. reuteri treatments, while reducing the abundance of E. coli on day 21 in
      the every 4th-day treatment. Real-time qPCR of ileal digesta showed an increase
      in Bifidobacterium spp. on day 14 for both L. reuteri I5007 treatments. An
      increase in the concentration of lactic acid and a lower pH was observed in the
      first 4-day treatment on day 7 and the every 4th day treatment on day 14. The
      relative abundance of mRNA for TGF-beta was increased while that for IFN-gamma
      was decreased in the mesenteric lymph nodes of piglets treated with L. reuteri
      every 4th day. In conclusion, early intervention with L. reuteri increases the
      presence of beneficial bacteria and decreases the presence of undesirable
      microbes in the lower gastrointestinal tract. The changes appear to be mediated
      by altering the intestinal pH through lactic acid production resulting in
      favorable bacterial species colonization. A prolonged duration of treatment (i.e.
      every 4th day) would appear to be superior to treatment only during the first 4
      days. 

PMID- 25775261
TI  - Evaluation of cord blood ischemia modified albumin in normal pregnancies and pre
      eclampsia.
AB  - OBJECTIVE: Pre-eclampsia is associated with ischemia and increased oxidative
      stress, which may lead to modification of plasma albumin to ischemia modified
      albumin (IMA). METHODS: IMA levels were estimated in cord blood of 30 newborns
      born to pre-eclamptic mothers and compared with 30 normal newborns. IMA was
      estimated colorimetrically and the results were compared statistically. RESULTS:
      The levels of IMA were found to be significantly higher (p < 0.001) in newborns
      born to pre-eclamptic mothers (0.835 +/- 0.02 ABSU) as compared to those born to
      normal mothers (0.325 +/- 0.01 ABSU). CONCLUSION: IMA may act as a marker of
      ischemia and oxidative stress in newborns delivered to pre-eclamptic mothers.

PMID- 25775263
TI  - Bound vortex dipoles generated at pinning centres by Meissner current.
AB  - One of the phenomena that make superconductors unique materials is the Meissner
      Ochsenfeld effect. This effect results in a state in which an applied magnetic
      field is expelled from the bulk of the material because of the circulation near
      its surface of resistance-free currents, also known as Meissner currents.
      Notwithstanding the intense research on the Meissner state, local fields due to
      the interaction of Meissner currents with pinning centres have not received much
      attention. Here we report that the Meissner currents, when flowing through an
      area containing a pinning centre, generate in its vicinity two opposite sense
      current half-loops producing a bound vortex-antivortex pair, which eventually may
      transform into a fully developed vortex-antivortex pair ultimately separated in
      space. The generation of such vortex dipoles by Meissner currents is not
      restricted to superconductors; similar topological excitations may be present in
      other systems with Meissner-like phases. 

PMID- 25775262
TI  - Homozygosity mapping and targeted sanger sequencing reveal genetic defects
      underlying inherited retinal disease in families from pakistan.
AB  - BACKGROUND: Homozygosity mapping has facilitated the identification of the
      genetic causes underlying inherited diseases, particularly in consanguineous
      families with multiple affected individuals. This knowledge has also resulted in
      a mutation dataset that can be used in a cost and time effective manner to screen
      frequent population-specific genetic variations associated with diseases such as
      inherited retinal disease (IRD). METHODS: We genetically screened 13 families
      from a cohort of 81 Pakistani IRD families diagnosed with Leber congenital
      amaurosis (LCA), retinitis pigmentosa (RP), congenital stationary night blindness
      (CSNB), or cone dystrophy (CD). We employed genome-wide single nucleotide
      polymorphism (SNP) array analysis to identify homozygous regions shared by
      affected individuals and performed Sanger sequencing of IRD-associated genes
      located in the sizeable homozygous regions. In addition, based on population
      specific mutation data we performed targeted Sanger sequencing (TSS) of frequent
      variants in AIPL1, CEP290, CRB1, GUCY2D, LCA5, RPGRIP1 and TULP1, in probands
      from 28 LCA families. RESULTS: Homozygosity mapping and Sanger sequencing of IRD
      associated genes revealed the underlying mutations in 10 families. TSS revealed
      causative variants in three families. In these 13 families four novel mutations
      were identified in CNGA1, CNGB1, GUCY2D, and RPGRIP1. CONCLUSIONS: Homozygosity
      mapping and TSS revealed the underlying genetic cause in 13 IRD families, which
      is useful for genetic counseling as well as therapeutic interventions that are
      likely to become available in the near future.

PMID- 25775264
TI  - Internalized stigma, emotional dysfunction and unusual experiences in young
      people at risk of psychosis.
AB  - AIMS: To investigate the relationship between internalized stigma, depression,
      social anxiety and unusual experiences in young people considered to be at risk
      of developing psychosis. METHODS: A total of 288 participants meeting criteria
      for an at-risk mental state were recruited as part of a multisite randomized
      controlled trial of cognitive behavioural therapy for people meeting criteria for
      an at risk mental state (ARMS). The sample was assessed at baseline and 6 months
      using measures of at risk mental states, internalized stigma, depression and
      social anxiety. RESULTS: The Personal Beliefs about Experiences Questionnaire was
      validated for use with an ARMS sample. Correlational analyses at baseline
      indicated significant relationships between internalized stigma and: (i)
      depression; (ii) social anxiety; (iii) distress associated with unusual
      psychological experiences; and (iv) suicidal thinking. Regression analysis
      indicates negative appraisals of unusual experiences contributed significantly to
      depression scores at 6-month follow up when controlling for baseline depression
      and unusual psychological experiences. CONCLUSIONS: These findings suggest that
      internalized stigma may contribute to the development and maintenance of
      depression in young people at risk of psychosis.

PMID- 25775265
TI  - High-resolution structure of the Escherichia coli ribosome.
AB  - Protein synthesis by the ribosome is highly dependent on the ionic conditions in
      the cellular environment, but the roles of ribosome solvation have remained
      poorly understood. Moreover, the functions of modifications to ribosomal RNA and
      ribosomal proteins have also been unclear. Here we present the structure of the
      Escherichia coli 70S ribosome at 2.4-A resolution. The structure reveals details
      of the ribosomal subunit interface that are conserved in all domains of life, and
      it suggests how solvation contributes to ribosome integrity and function as well
      as how the conformation of ribosomal protein uS12 aids in mRNA decoding. This
      structure helps to explain the phylogenetic conservation of key elements of the
      ribosome, including post-transcriptional and post-translational modifications,
      and should serve as a basis for future antibiotic development. 

PMID- 25775266
TI  - How a homolog of high-fidelity replicases conducts mutagenic DNA synthesis.
AB  - All DNA replicases achieve high fidelity by a conserved mechanism, but each
      translesion polymerase carries out mutagenic DNA synthesis in its own way. Here
      we report crystal structures of human DNA polymerase nu (Pol nu), which is
      homologous to high-fidelity replicases yet is error prone. Instead of a simple
      open-to-closed movement of the O helix upon binding of a correct incoming
      nucleotide, Pol nu has a different open state and requires the finger domain to
      swing sideways and undergo both opening and closing motions to accommodate the
      nascent base pair. A single-amino acid substitution in the O helix of the finger
      domain improves the fidelity of Pol nu nearly ten-fold. A unique cavity and the
      flexibility of the thumb domain allow Pol nu to generate and accommodate a looped
      out primer strand. Primer loop-out may be a mechanism for DNA trinucloetide
      repeat expansion. 

PMID- 25775267
TI  - Human DNA polymerase theta grasps the primer terminus to mediate DNA repair.
AB  - DNA polymerase theta protects against genomic instability via an alternative end
      joining repair pathway for DNA double-strand breaks. Polymerase theta is
      overexpressed in breast, lung and oral cancers, and reduction of its activity in
      mammalian cells increases sensitivity to double-strand break-inducing agents,
      including ionizing radiation. Reported here are crystal structures of the C
      terminal polymerase domain from human polymerase theta, illustrating two
      potential modes of dimerization. One structure depicts insertion of ddATP
      opposite an abasic-site analog during translesion DNA synthesis. The second
      structure describes a cognate ddGTP complex. Polymerase theta uses a specialized
      thumb subdomain to establish unique upstream contacts to the primer DNA strand,
      including an interaction with the 3'-terminal phosphate from one of five
      distinctive insertion loops. These observations demonstrate how polymerase theta
      grasps the primer to bypass DNA lesions or extend poorly annealed DNA termini to
      mediate end-joining. 

PMID- 25775269
TI  - MicroRNA844-Guided Downregulation of Cytidinephosphate Diacylglycerol Synthase3
      (CDS3) mRNA Affects the Response of Arabidopsis thaliana to Bacteria and Fungi.
AB  - Despite the fact that a large number of miRNA sequences have been determined in
      diverse plant species, reports demonstrating the functional roles of miRNAs in
      the plant response to pathogens are severely limited. Here, Arabidopsis thaliana
      miRNA844 (miR844) was investigated for its functional role in the defense
      response to diverse pathogens. Transgenic Arabidopsis plants overexpressing
      miR844 (35S::miR844) displayed much more severe disease symptoms than the wild
      type plants when challenged with the bacterium Pseudomonas syringae pv. tomato
      DC3000 or the fungus Botrytis cinerea. By contrast, a loss-of-function mir844
      mutant showed an enhanced resistance against the pathogens. Although no cleavage
      was observed at the predicted cleavage site of the putative target mRNA,
      cytidinephosphate diacylglycerol synthase3 (CDS3), cleavage was observed at 6,
      12, 21, or 52 bases upstream of the predicted cleavage site of CDS3 mRNA, and the
      level of CDS3 mRNA was downregulated by the overexpression of miR844, implying
      that miR844 influences CDS3 transcript level. To further confirm that the miR844
      mediated defense response was due to the decrease in CDS3 mRNA level, the disease
      response of a CDS3 loss-of-function mutant was analyzed upon pathogen challenge.
      Increased susceptibility of both cds3 mutant and 35S::miR844 plants to pathogens
      confirmed that miR844 affected the defense response by downregulating CDS3 mRNA.
      The expression of miR844 was decreased, and the CDS3 transcript level increased
      upon pathogen challenge. Taken together, these results provide evidence that
      downregulation of miR844 and a concomitant increase in CDS3 expression is a
      defensive response of Arabidopsis to bacteria and fungi. 

PMID- 25775270
TI  - Characterization of Cell-Death-Inducing Members of the Pectate Lyase Gene Family
      in Phytophthora capsici and Their Contributions to Infection of Pepper.
AB  - Pectate lyases (PL) play a critical role in pectin degradation. PL have been
      extensively studied in major bacterial and fungal pathogens of a wide range of
      plant species. However, the contribution of PL to infection by oomycete pathogens
      remains largely unknown. Here, we cloned 22 full-length pectate lyase (PcPL)
      genes from a highly aggressive strain of Phytophthora capsici SD33. Of these, PVX
      agroinfiltration revealed that 12 PcPL genes were found to be highly induced
      during infection of pepper by SD33 but the induction level was twofold less in a
      mildly aggressive strain, YN07. The four genes with the highest transcript levels
      as measured by by quantitative reverse-transcription polymerase chain reaction
      (PcPL1, PcPL15, PcPL16, and PcPL20) also produced a severe cell death response
      following transient expression in pepper leaves but the other eight PcPL genes
      did not. Overexpression of these four genes increased the virulence of SD33 on
      pepper slightly, and increased it more substantially during infection of tobacco.
      Overexpression of the genes in YN07 restored its aggressiveness to near that of
      SD33. Gene silencing experiments with the 12 PcPL genes produced diverse patterns
      of silencing of PcPL genes, from which it could be inferred from regression
      analysis that PcPL1, PcPL16, and PcPL20 could account for nearly all of the
      contributions of the PcPL genes to virulence. 

PMID- 25775268
TI  - Structural insights into the role of rRNA modifications in protein synthesis and
      ribosome assembly.
AB  - We report crystal structures of the Thermus thermophilus ribosome at 2.3- to 2.5
      A resolution, which have enabled modeling of rRNA modifications. The structures
      reveal contacts of modified nucleotides with mRNA and tRNAs or protein pY, and
      contacts within the ribosome interior stabilizing the functional fold of rRNA.
      Our work provides a resource to explore the roles of rRNA modifications and
      yields a more comprehensive atomic model of a bacterial ribosome. 

PMID- 25775271
TI  - The Sinorhizobium (Ensifer) fredii HH103 Type 3 Secretion System Suppresses Early
      Defense Responses to Effectively Nodulate Soybean.
AB  - Plants that interact with pathogenic bacteria in their natural environments have
      developed barriers to block or contain the infection. Phytopathogenic bacteria
      have evolved mechanisms to subvert these defenses and promote infection. Thus,
      the type 3 secretion system (T3SS) delivers bacterial effectors directly into the
      plant cells to alter host signaling and suppress defenses, providing an
      appropriate environment for bacterial multiplication. Some rhizobial strains
      possess a symbiotic T3SS that seems to be involved in the suppression of host
      defenses to promote nodulation and determine the host range. In this work, we
      show that the inactivation of the Sinorhizobium (Ensifer) fredii HH103 T3SS
      negatively affects soybean nodulation in the early stages of the symbiotic
      process, which is associated with a reduction of the expression of early
      nodulation genes. This symbiotic phenotype could be the consequence of the
      bacterial triggering of soybean defense responses associated with the production
      of salicylic acid (SA) and the impairment of the T3SS mutant to suppress these
      responses. Interestingly, the early induction of the transcription of GmMPK4,
      which negatively regulates SA accumulation and defense responses in soybean via
      WRKY33, could be associated with the differential defense responses induced by
      the parental and the T3SS mutant strain. 

PMID- 25775272
TI  - Phytosulfokine Is Involved in Positive Regulation of Lotus japonicus Nodulation.
AB  - Phytosulfokine (PSK) is a tyrosine-sulfated peptide that is widely distributed in
      plants, participating in cell proliferation, differentiation, and innate
      immunity. The potential role of PSK in nodulation in legumes has not been
      reported. In this work, five PSK precursor genes were identified in Lotus
      japonicas, designated as LjPSK1 to LjPSK5. Three of them (LjPSK1, LjPSK4, and
      LjPSK5) were found to be expressed in nitrogen-fixing root nodules. LjPSK1 and
      LjPSK4 were not induced at the early stage of nodulation. Interestingly, while
      the expression of LjPSK4 was also found in spontaneous nodules without rhizobial
      colonization, LjPSK1 was not induced in these pseudo nodules. Promoter-beta
      glucuronidase analysis revealed that LjPSK1 was highly expressed in enlarged
      symbiotic cells of nodules. Exogenous addition of 1 1M synthetic PSK peptide
      resulted in increased nodule numbers per plant. Consistently, the number of
      mature nodules but not the events of rhizobial infection and nodule initiation
      was increased by overexpressing LjPSK1 in transgenic hairy roots, in which the
      expression of jasmonate-responsive genes was found to be repressed. These results
      suggest that PSK is a new peptide signal that regulates nodulation in legumes,
      probably through cross-talking with other phytohormones. 

PMID- 25775273
TI  - The continuity of the body: hypothesis of treatment of the five diaphragms.
AB  - The diaphragm muscle should not be seen as a segment but as part of a body
      system. This muscle is an important crossroads of information for the entire
      body, from the trigeminal system to the pelvic floor, passing from thoracic
      diaphragm to the floor of the mouth: the network of breath. Viola Frymann first
      spoke of the treatment of three diaphragms, and more recently four diaphragms
      have been discussed. Current scientific knowledge has led to discussion of the
      manual treatment of five diaphragms. This article highlights the anatomic
      connections and fascial and neurologic aspects of the diaphragm muscle, with four
      other structures considered as diaphragms: that is, the five diaphragms. The
      logic of the manual treatment proposed here is based on a concept and diagnostic
      work that should be the basis for any area of the body: The patient never just
      has a localized symptom but rather a system that adapts to a question. 

PMID- 25775275
TI  - NHERF1/EBP50 is an organizer of polarity structures and a diagnostic marker in
      ependymoma.
AB  - NHERF1/EBP50, an adaptor protein required for epithelial morphogenesis, has been
      implicated in the progression of various human malignancies. NHERF1-deficient
      mice have intestinal brush border structural defects and we report here that they
      also have disorganized ependymal cilia with development of non-obstructive
      hydrocephalus. Examination of mouse and human brain tissues revealed highest
      NHERF1 expression at the apical plasma membrane of ependymal cells. In ependymal
      tumors, NHERF1 expression was retained in polarized membrane structures, such as
      microlumens, rosettes and canals, where it co-localized with some of its ligands,
      such as moesin and PTEN. Analysis of a comprehensive panel of 113 tumors showed
      robust NHERF1 labeling of microlumens in 100% of ependymomas, subependymomas, and
      pediatric anaplastic ependymomas, and in 67% of adult anaplastic ependymomas.
      NHERF1 staining was present in 35% of ependymoma cases that lacked reactivity for
      EMA, the routine immunohistochemical marker used for ependymoma diagnosis. NHERF1
      labeling of microlumens was either absent or rarely seen in other types of brain
      tumors analyzed, denoting NHERF1 as a reliable diagnostic marker of ependymal
      tumors. Anaplastic foci and a subset of adult anaplastic ependymomas showed
      complete absence of NHERF1-labeled polarity structures, consistent with a loss of
      differentiation in these aggressive tumors. These data highlight a role for
      NHERF1 in ependymal morphogenesis with direct application to the diagnosis of
      ependymal tumors. 

PMID- 25775276
TI  - Uptake and bioconversion of stereoisomeric dipeptide prodrugs of ganciclovir by
      nanoparticulate carriers in corneal epithelial cells.
AB  - PURPOSE: The objective of this study is to investigate cellular uptake of prodrug
      loaded nanoparticle (NP). Another objective is to study bioconversion of
      stereoisomeric dipeptide prodrugs of ganciclovir (GCV) including L-Val-L-Val-GCV
      (LLGCV), L-Val-D-Val-GCV (LDGCV) and d-Val-l-Val-GCV (DLGCV) in human corneal
      epithelial cell (HCEC) model. METHODS: Poly(D,L-lactic-co-glycolic acid) (PLGA)
      NP encapsulating prodrugs of GCV were formulated under a double emulsion method.
      Fluorescein isothiocyanate isomer-PLGA conjugates were synthesized to fabricate
      biocompatible fluorescent PLGA NP. Intracellular uptake of FITC-labeled NP was
      visualized by a fluorescent microscope in HCEC cells. RESULTS: Fluorescent PLGA
      NP and non-fluorescent NP display similar hydrodynamic diameter in the range of
      115-145 nm with a narrow particle size distribution and zeta potentials around 
      13 mV. Both NP types showed identical intracellular accumulation in HCEC cells.
      Maximum uptake (around 60%) was noted at 3 h for NP. Cellular uptake and
      intracellular accumulation of prodrugs are significantly different among three
      stereoisomeric dipeptide prodrugs. The microscopic images show that NPs are
      avidly internalized by HCEC cells and distributed throughout the cytoplasm
      instead of being localized on the cell surface. Following cellular uptake,
      prodrugs released from NP gradually bioreversed into parent drug GCV. LLGCV
      showed the highest degradation rate, followed by LDGCV and DLGCV. CONCLUSION:
      LLGCV, LDGCV and DLGCV released from NP exhibited superior uptake and
      bioreversion in corneal cells.

PMID- 25775274
TI  - Effect of Vitamin D Supplementation on Blood Pressure: A Systematic Review and
      Meta-analysis Incorporating Individual Patient Data.
AB  - IMPORTANCE: Low levels of vitamin D are associated with elevated blood pressure
      (BP) and future cardiovascular events. Whether vitamin D supplementation reduces
      BP and which patient characteristics predict a response remain unclear.
      OBJECTIVE: To systematically review whether supplementation with vitamin D or its
      analogues reduce BP. DATA SOURCES: We searched MEDLINE, CINAHL, EMBASE, Cochrane
      Central Register of Controlled Trials, and http://www.ClinicalTrials.com
      augmented by a hand search of references from the included articles and previous
      reviews. Google was searched for gray literature (ie, material not published in
      recognized scientific journals). No language restrictions were applied. The
      search period spanned January 1, 1966, through March 31, 2014. STUDY SELECTION:
      We included randomized placebo-controlled clinical trials that used vitamin D
      supplementation for a minimum of 4 weeks for any indication and reported BP data.
      Studies were included if they used active or inactive forms of vitamin D or
      vitamin D analogues. Cointerventions were permitted if identical in all treatment
      arms. DATA EXTRACTION AND SYNTHESIS: We extracted data on baseline demographics,
      25-hydroxyvitamin D levels, systolic and diastolic BP (SBP and DBP), and change
      in BP from baseline to the final follow-up. Individual patient data on age, sex,
      medication use, diabetes mellitus, baseline and follow-up BP, and 25
      hydroxyvitamin D levels were requested from the authors of the included studies.
      For trial-level data, between-group differences in BP change were combined in a
      random-effects model. For individual patient data, between-group differences in
      BP at the final follow up, adjusted for baseline BP, were calculated before
      combining in a random-effects model. MAIN OUTCOMES AND MEASURES: Difference in
      SBP and DBP measured in an office setting. RESULTS: We included 46 trials (4541
      participants) in the trial-level meta-analysis. Individual patient data were
      obtained for 27 trials (3092 participants). At the trial level, no effect of
      vitamin D supplementation was seen on SBP (effect size, 0.0 [95% CI, -0.8 to 0.8]
      mm Hg; P=.97; I2=21%) or DBP (effect size, -0.1 [95% CI, -0.6 to 0.5] mm Hg;
      P=.84; I2=20%). Similar results were found analyzing individual patient data for
      SBP (effect size, -0.5 [95% CI, -1.3 to 0.4] mm Hg; P=.27; I2=0%) and DBP (effect
      size, 0.2 [95% CI, -0.3 to 0.7] mm Hg; P=.38; I2=0%). Subgroup analysis did not
      reveal any baseline factor predictive of a better response to therapy.
      CONCLUSIONS AND RELEVANCE: Vitamin D supplementation is ineffective as an agent
      for lowering BP and thus should not be used as an antihypertensive agent.

PMID- 25775277
TI  - The Role of Active Site Residues in ATP Binding and Catalysis in the
      Methanosarcina thermophila Acetate Kinase.
AB  - Acetate kinase (ACK), which catalyzes the reversible phosphorylation of acetate
      by ATP, is a member of the acetate and sugar kinase/heat shock cognate/actin
      (ASKHA) superfamily. ASKHA family members share a common core fold that includes
      an ATPase domain with five structural motifs. The PHOSPHATE1 motif has previously
      been shown to be important for catalysis. We have investigated the role of two of
      these motifs in the Methanosarcina thermophila ACK (MtACK) and have shown that
      residues projecting into the ACK active site from the PHOSPHATE2 and ADENOSINE
      loops and a third highly conserved loop designated here as LOOP3 play key roles
      in nucleotide triphosphate (NTP) selection and utilization. Alteration of Asn211
      of PHOSPHATE2, Gly239 of LOOP3, and Gly331 of ADENOSINE greatly reduced
      catalysis. In particular, Gly331, which is highly conserved throughout the ASKHA
      superfamily, has the greatest effect on substrate selection. Alteration at this
      site strongly skewed MtACK toward utilization of purines over pyrimidines, unlike
      the wild type enzyme that shows broad NTP utilization. Further investigation into
      differences between the ATPase domain in MtACK and other acetate kinases that
      show different substrate preferences will provide us with a better understanding
      of the diversity of phosphoryl donor selection in this enzyme family. 

PMID- 25775278
TI  - The National Institutes of Health and guidance for reporting preclinical
      research.
AB  - The quality of reporting clinical and preclinical research is not optimal.
      Reporting guidelines can help make reports of research more complete and
      transparent, thus increasing their value and making them more useful to all
      readers. Getting reporting guidelines into practice is complex and expensive, and
      involves several stakeholders, including prospective authors, peer reviewers,
      journal editors, guideline developers, and implementation scientists. Working
      together will help ensure their maximum uptake and penetration. We are all
      responsible for helping to ensure that all research is reported so completely
      that it is of value to everybody. Please see related article:
      http://dx.doi.org/10.1186/s12916-015-0266-y.

PMID- 25775279
TI  - [Rh(III)(Cp*)]-catalyzed cascade arylation and chlorination of alpha
      diazocarbonyl compounds with arylboronic acids and N-chlorosuccinimide for facile
      synthesis of alpha-aryl-alpha-chloro carbonyl compounds.
AB  - A Rh(III)-catalyzed cascade arylation and chlorination of alpha-diazocarbonyl
      compounds with arylboronic acids and N-chlorosuccinimide was achieved. The
      reaction exhibits excellent functional group tolerance on the organoboron and the
      diazo reagents; the functionalized alpha-aryl-alpha-chlorocarbonyl compounds were
      obtained in up to 86% yields. The cascade reaction should involve migratory
      carbene insertion of arylrhodium(III) to form some reactive rhodium(III)
      diketonate complexes. Its subsequent reaction with N-chlorosuccinmide afforded
      the alpha-chlorocarbonyl products. 

PMID- 25775281
TI  - [Pulmonary thromboembolism: incidence, physiopathology, diagnosis and treatment].
AB  - AIM: The objective of this work was to review current data about the
      pathophysiology, clinical features, and treatment of pulmonary thromboembolism.
      Venous thromboembolism (VTE) remains a major challenge in hospitalised especially
      the care of critically ill patients. Pulmonary embolism (PE) is the major
      complication of VTE. By occluding the pulmonary arterial bed it may lead to acute
      life-threatening but potentially reversible right ventricular failure. The
      outcome of patients with PE is quite variable depending primarily on the cardio
      respiratory status and the embolus size. PE is a difficult diagnosis that may be
      missed because of non-specific clinical presentation. Clinical signs include
      hypoxia, tachypnea, and tachycardia. Severe cases of untreated PE can lead to
      circulatory instability, and sudden death. However, in ICU, most of patients
      require sedation and mechanical ventilation. The clinical manifestations usually
      observed in this condition (PE) cannot be exhibited by these patients and
      clinical presentation is usually atypical. For these reasons, the diagnosis of PE
      is usually suspected when un-explicated hypoxemia and/or shock and arterial
      hypotension were observed. Positive diagnosis is based on these clinical findings
      in combination with laboratory tests and imaging studies. D-dimer testing is of
      clinical use when there is a suspicion of DVT or pulmonary embolism PE. In
      Emergency department, a negative D-dimer test will virtually rule out
      thromboembolism with a negative predictive value at 95 to 98%. In massive and
      submassive PE, dysfunction of the right side of the heart can be seen on
      echocardiography. While the gold standard for diagnosis is the finding of a clot
      on pulmonary angiography, CT pulmonary angiography is the most commonly used
      imaging modality today. When the diagnosis is confirmed, anticoagulant therapy is
      the mainstay of treatment. Acutely, supportive treatments a pivotal role in the
      management of patients with PE. Severe cases may require thrombolysis with drugs
      such as tissue plasminogen activator (tPA) or may require surgical intervention
      via pulmonary thrombectomy. Prevention is highly warranted.

PMID- 25775280
TI  - Genome-wide association study identifies a new susceptibility locus for cleft lip
      with or without a cleft palate.
AB  - Nonsyndromic cleft lip with or without a cleft palate (NSCL/P) is among the most
      common human congenital birth defects and imposes a substantial physical and
      financial burden on affected individuals. Here, we conduct a case-control-based
      GWAS followed by two rounds of replication; we include six independent cohorts
      from China to elucidate the genetic architecture of NSCL/P in Chinese
      populations. Using this combined analysis, we identify a new locus at 16p13.3
      associated with NSCL/P: rs8049367 between CREBBP and ADCY9 (odds ratio=0.74,
      P=8.98 * 10(-12)). We confirm that the reported loci at 1q32.2, 10q25.3, 17p13.1
      and 20q12 are also involved in NSCL/P development in Chinese populations. Our
      results provide additional evidence that the rs2235371-related haplotype at
      1q32.2 could play a more important role than the previously identified causal
      variant rs642961 in Chinese populations. These findings provide information on
      the genetic basis and mechanisms of NSCL/P. 

PMID- 25775282
TI  - [Elastography assessment of the cervix during cervical maturation].
AB  - BACKGROUND: The issue of cervical tissue imaging is to enable the provision of
      Obstetricians an objective tool for measuring cervical changes more accurate than
      the vaginal touch. Hitachi software "Real-time Tissue Elastography" allows an
      analysis of tissue elasticity, evaluated on a Young's modulus theory. This
      imagery evaluated for mammary tumors and liver changes elasticity, would
      objectively show changes in cervical consistency. AIMS: The authors of the
      following work have attempted to: - Assess the usefulness of elastography in the
      uterine cervix examination. - Compare the modifications of the cervical module of
      elasticity before and during the maturation by prostaglandins indicated for
      medical reason with those raised in the clinical examination (score of Bishop).
      METHODS: It is about a non-interventional feasibility study with regulation of
      the machine, realized in forward-looking. We included 30 patients scheduled for a
      cervical maturation by prostaglandins for medical indication. We realized a
      measure of the cervical module of elasticity during an endo-vaginal ultrasound
      for measure of the cervix before the pose of prostaglandins, 6 hours then 12
      hours after the stake in contact and we compared the measure every time with the
      score of bishop. RESULTS: All the patients who presented an index of high
      softening entered labor within the 3 hours following the examination.
      Furthermore, the modifications observed on the index of softening were correlated
      to those of the score of Bishop. CONCLUSION: The performance of the images of
      elastography with these regulations allowed a good confrontation of the results
      during the evaluation of the feasibility of the technique with the score of
      Bishop during cervical maturation. This promising technique remains a technique
      of research. Forward-looking studies on wide series of patients are going to be
      able to estimate the elastography as an additional and objective informer of the
      cervical maturation.

PMID- 25775283
TI  - [Circadian clock genes expression in peripheral blood mononuclear cells of
      comatose patients].
AB  - BACKGROUND: Recently circadian clock genes have been identified in humans but
      information regarding their expression has remained very limited. The evaluation
      of circadian variations in the expression of clock genes in humans seems to be a
      major importance both from a fundamental point of view as a diagnostic and
      therapeutic perspective. In this context, several works including ours have
      described the fluctuation of clock genes. AIMS: describing rhythmic expression of
      clock genes in intensive care units patients during 24h and we tried to determine
      the effect of the absence of synchronizers such as light/ dark cycle on these
      rhythms. METHODS: 15 patients received care in private room in intensive care
      units in the hospital Sahloul (5 comatous and 10 non comatous patients). For RNA
      isolation we used peripheral blood mononuclear cells which represent an ideal
      material to investigate non-invasively the human clock at the molecular level.
      RESULTS: In the present study, we noticed that clock genes mRNA exhibit a
      circadian expression in comatose patients, while the rhythmicity of some studied
      genes disappeared in non-comatose patients. CONCLUSION: The disturbance of the
      rhythmic fluctuation of the clock genes could be the result of the effect of
      surgery on some biological rhythms as it could be explained by the lack of
      synchronizers in intensive care units such as light/dark cycle.

PMID- 25775284
TI  - [Molecular characterization of Lynch syndrome in Tunisia].
AB  - BACKGROUND: High rates of early colorectal cancers (CRC) are observed in Tunisia
      suggesting genetic susceptibility. Nevertheless, up to now no molecular studies
      have been performed in the Tunisian population. AIM: To evaluate the clinical and
      genetic characteristics of Tunisian families suspected of hereditary nonpolyposis
      colorectal cancer (HNPCC) and to identify new tumoral markers for CRC
      susceptibility leading to distinguish patients with sporadic CRC from those with
      familial CRC, like HNPCC. METHODS: 31 unrelated families suspected of HNPCC were
      screened for germline mutations in MMR genes. We have also analyzed tumoral
      phenotype and the genetic characteristics of tumors from 51 patients with CRC
      meeting the Bethesda criteria. RESULTS: 10 different germ line mutations, 8 of
      which were novel, were identified in 11 out of the 31 families (35.5%), 5 in MSH2
      and 5 in MLH1. Our results showed that MUC5AC expression was more frequent in
      patients with family history of CRC (p=0.039). CONCLUSION: The analysis of MUC5AC
      expression might be very beneficial in the detection of Tunisian patients with
      high susceptibility to CRC.

PMID- 25775285
TI  - [Clinical and sociodemographic characteristics of sudden cardiac death victims in
      northen Tunisia].
AB  - BACKGROUND: The sudden cardiac death remains a major public health problem. This
      dramatic event has not been well investigated in Tunisia. AIM: The aim of this
      work is to study the epidemiological and socio demographic characteristics of
      Tunisian victims. METHODS: We prospectively collected clinical, socio demographic
      and pathology data of victims of sudden cardiac death occurring in the northern
      Tunisia from October 2010 to September 2012. RESULTS: The study population
      included 392 men and 108 women with a mean age of 52,2 + / - 15,8 years. Three
      quarters of the victims were sedentary, 57,9% were smoker and a family history of
      sudden death was identified in 9,8% of cases. Half of victims had a primary
      school education, only 8,4% has a university education, 65,6% of subjects lived
      in urban areas and 64% of victims were married. The vast majority of deaths had
      occurred either in a public place (41,4%) or at home (36,6%). The most frequent
      circumstance of death was at rest (67%). Only 5,1% of victims were transported by
      emergency medical services and 12,1% by civil protection. Ischemic heart disease
      was the leading cause of death with 267 cases; however a negative autopsy was
      denoted in 13,9% of victims. CONCLUSIONS: Victims of sudden cardiac death in
      northern Tunisia were relatively young with a male predominance. Physical
      inactivity and smoking were the most common risk factors for cardiovascular
      disease. The majority of victims were married, had an urban origin and a low
      level of education. Ischemic heart disease was the first etiology of sudden
      death.

PMID- 25775286
TI  - [Contribution of dynamic radiographs in atlantoaxial subluxation in rheumatoid
      arthritis].
AB  - BACKGROUND: Cervical spine (CS) involvement is common during rheumatoid arthritis
      (RA) and it is distinguished by its potential gravity. AIM: To determinate the
      occurrence of atlantoaxial subluxation (AAS) by dynamic incidences X-Ray and to
      assess its predictive factors. METHODS: Our study included a cohort of 40
      patients carrying RA, who fulfilled the American College of Rheumatology
      criteria, for more than 2 years. All patients had a complete physical and
      laboratory evaluation. Radiological evaluation included CS radiographs in
      anteroposterior, lateral, and lateral in full flexion and extension views.
      RESULTS: The occurrence of CS involvement was about 47.5% by XRay dominated by
      AAS which found in 42,5% of the cases. Among AAS, anterior AAS was the most
      frequent with a prevalence of 22,5% followed by lateral AAS in 12,5% then
      vertical and rotatory AAS in 10% of cases each one and posterior AAS in 2,5% of
      the cases. Comparison between patients with and without CS involvement indicated
      the presence of two predictive factors: the sharp modified score and the C -
      reactive protein (p=0.002 and p=0.004 respectively). CONCLUSION: Our study
      demonstrated that AAS is frequent in RA particularly in active forms with
      structural lesions. AAS can be asymptomatic, for this reason systematic diagnosis
      by X-Ray with dynamic views is important.

PMID- 25775287
TI  - [The diagnosis of COPD is recommendation dependent].
AB  - BACKGROUND: Different spirometric criteria are recommended to diagnosis chronic
      obstructive pulmonary disease (COPD): -American Thoracic Society/European
      Respiratory Society (ATS/ERS), Global initiative for chronic Obstructive Lung
      Disease (GOLD): a post bronchodilator (PBD) ratio between the 1st second Forced
      Expiratory Volume and Forced Vital Capacity (FEV1/FVC) < 0.70; -Thoracic Society
      of Australia and New Zealand (ANZTS): a PBD FEV1/FVC < 0.70 and a PBD FEV1 < 80%;
      -British Thoracic Society (BTS): a before BD (BBD) FEV1/FVC < 0.70 and a BBD FEV1
      < 80%; -Old criterion retained, till 2010, by the French Society of Pneumology
      (SPLF): a PBD ratio between FEV1 and slow vital capacity < 0.70. AIM: To
      determine, according to the different recommendations, the percentage of smokers
      having COPD among a population of smokers of more than 40 Packets/Year (PY)
      addressed for plethysmography. METHODS: The plethysmographic data of 531
      consecutive stable male smokers that underwent reversibility testing (400 ug of
      Salbutamol(r)) were analyzed. RESULTS: The mean +/- SD of age, cigarettes
      consumption, PBD FEV1 (%), were, respectively, 61 +/- 11 Yr, 64 +/- 20 PY and 52
      +/- 21%. The percentages of subjects having COPD according to the above criteria
      were 75.5% (SPLF old criterion); 71.2% (ATS/ERS, GOLD); 70.8% (BTS) and 69.7%
      (ANZTS). CONCLUSION: The diagnosis of COPD depends on which guidelines are used
      for defining the disease. This forms a barrier to early diagnosis, affects public
      health decisions and wrong planning strategies.

PMID- 25775288
TI  - [Surgical complications of colostomies].
AB  - BACKGROUND: The colostomy may be terminal or lateral, temporary or permanent. It
      may have psychological, medical or surgical complications. AIM: reporting the
      incidence of surgical complications of colostomies, their therapeutic management
      and trying to identify risk factors for their occurrence. METHODS: A
      retrospective study for a period of 5 years in general surgery department, Habib
      Bourguiba hospital, Sfax, including all patients operated with confection of a
      colostomy. Were then studied patients reoperated for stoma complication. RESULTS:
      Among the 268 patients who have had a colostomy, 19 patients (7%) developed
      surgical stoma complications. They had a mean age of 59 years, a sex ratio of 5.3
      and a 1-ASA score in 42% of cases. It was a prolapse in 9 cases (reconfection of
      the colostomy: 6 cases, restoration of digestive continuity: 3 cases), a necrosis
      in 5 cases (reconfection of the colostomy), a plicature in 2 cases (reconfection
      of the colostomy) a peristomal abscess in 2 cases (reconfection of the colostomy:
      1 case, restoration of digestive continuity: 1 case) and a strangulated
      parastomal hernia in 1 case (herniorrhaphy). The elective incision and the
      perineal disease were risk factors for the occurrence of prolapse stomial.
      CONCLUSION: Surgical complications of colostomies remain a rare event. Prolapse
      is the most common complication, and it is mainly related to elective approach.
      Reoperation is often required especially in cases of early complications, with
      usually uneventful postoperative course.

PMID- 25775289
TI  - [Diffuse oesophageal spasms: results of a retrospective manometric study].
AB  - BACKGROUND: Diffuse esophageal spasms is a primary motor disrder of the esophagus
      of unknown etiology characterized by intermettent peristalsis. This is rare
      condition which represents 3-5% if primary disorders of the esophagus. Diagnosis
      and treatment of this entity are difficult. AIMS: To evaluate the frequency and
      the clinical and the manometric features of diffuse esophageal spasms. METHODS:
      We conducted a retrospective study related to esophageal manometry performed
      between January 2000 and December 2011 regardless of the indication. Patients
      with meeting criteria for diffuse esophageal spasms (> 20 % simultaneous waves
      with greater than 30 mmHg pressure in the esophagus) were included. RESULTS: Out
      of 1188 patients, 13 (1,09 %) met the manometric criteria for diffuse esophageal
      spasms. It was 8 women and 5 men with a median age of 57 years. Dysphagia was the
      most relevant symptom and chest pain was only noted in 1 patient. The frequency
      of simultaneous waves was between 20 and 80 %. The pressure of the lower
      esophageal sphincter was normal in most cases. CONCLUSION: In this Tunisian
      manometric study, the diffuse esophageal spasms is rare. Dysphagia was the most
      relevant symptom and the pressure of the lower esophageal sphincter was normal in
      most cases.

PMID- 25775290
TI  - Risk factors for anastomotic leakage after anterior resection for rectal
      adenocarcinoma.
AB  - BACKGROUND: Anastomotic leakage (AL) is an important cause of morbidity after
      surgery for rectal cancer. AIM: to analyze the risk factors associated with
      anastomotic leakage after anterior resection for rectal adenocarcinoma. METHODS:
      We collected data from all the patients who had surgical resection with an
      anastomosis, for rectal adenocarcinoma at the Surgical Clinic C (Ibn Sina
      Hospital, Rabat, Morocco), between January 2001 and December 2010. The
      associations between variables and anastomotic leakage were studied using
      univariate and multivariate analysis. RESULTS: Our study included 130 patients.
      Anastomotic leakage occurred in 28 patients (21.5%). Univariate and multivariate
      analysis showed that the rate of anastomotic leakage was significantly higher in
      patients who received preoperative radiotherapy (34.2% vs. 12 %, p = 0.002 - OR
      3.8 - CI 95%: 1.5 - 9.4). There was no significant difference in the rate of AL
      between patients with or without a protective stoma. In the group of patients
      with AL, the rate of reoperation was significantly lower in patients with a stoma
      protection (31.8% vs. 83.3%, p = 0.04). CONCLUSION: Radiotherapy is a risk factor
      for anastomotic leakage. The systematic design of a protective stoma in patients
      receiving neoadjuvant radiotherapy is advisable to reduce the rate of
      reoperations associated with AL.

PMID- 25775291
TI  - Opium consumption and lipid and glucose parameters in diabetic patients with
      acute coronary syndrome: a survey in northern Iran.
AB  - BACKGROUND: A traditional belief is common among people of the Middle East
      countries regarding anti-diabetic and anti-dyslipidemic effect of opium. AIM: To
      assess the association between opium consumption and lipid and glucose parameters
      in diabetic patients of northern Iran. METHODS: Ninety-seven diabetic patients
      admitted to Critical Care Unit (CCU) of Rouhani and Shahid Beheshti hospitals
      from 2006 to 2007 were enrolled in this cross-sectional study. Forty-eight
      patients with regular opium consumption of three days a week for more than 6
      months were considered as case group. A non-opium diabetic patient admitted in
      the same hospital was considered as control for each opium addict patient. Total
      cholesterol, Triglyceride, LDL, HDL, FBS, HbA1c were measured in all patients.
      Student t-test, Mann-Whitney U, Chi-square test and Spearman correlation were
      used for data analysis. RESULT: The mean age of patients was 64.32 +/- 11.47
      years. There were no significant differences between the serum level of lipid and
      glucose indices between the two groups (P>0.05). CONCLUSION: The effect of opium
      consumption on diabetes and dyslipidemia are not protective.

PMID- 25775292
TI  - [Management of anorexia nervosa in a Tunisian case].
AB  - BACKGROUND: Anorexia nervosa is a complex psychiatric illness that can lead to
      severe physical complications. OBJECTIVE: This work aimed to study the approach
      taken by the child psychiatry service of Razi hospital in the management of
      anorexia nervosa and to compare it with international recommendation. METHODS: We
      propose to illustrate by a case report and review international recommendations
      on this topic while undertaking a review of the literature based on a Medline
      search using the following keywords: anorexia, nervosa adolescence, management,
      guidelines. RESULTS: Case report: AS, 16 years old, addressed to us by the school
      doctor for management of anorexia nervosa evolving for two years without
      improvement through outpatient care. His condition was considered precarious
      requiring urgent care in a medical hospital. She was then hospitalized at the
      Institute of Nutrition with a weight contract to achieve, She received a gradual
      refueling strongly denied. We have provided a psychological support by moving on
      site three times a week to help establish a good therapeutic alliance. After
      three weeks, the teenager has reached an acceptable weight for its output to the
      hospital and additional support at the outpatient child psychiatry with
      supportive psychotherapy. Two months later, she developed depression because of
      the weight gain. The appointment at the dietician was continued three months
      after hospitalization. At 10 months of the hospitalization, the girl had good
      grades and was not amenorrheic. However, on the psychological level she kept the
      same traits and intrafamilial relationships were marked by the seal of the
      manipulation. Subsequently, the teenager has spaced the consultations then lost
      sight. Currently, at 15 months of the hospitalization, parents describe a
      relapse, with a dietary restriction without amenorrhea ad a refusal to take
      weight. In management of this patient, we followed the recommendations of the
      literature namely those of the High Authority of Health and NICE (National
      Institute for Clinical Excellence) which recommend a target tracking of anorexia
      nervosa, the establishment of a multidisciplinary team care, a long
      hospitalization with a weight contract, support and not effective. Similarly, for
      children and adolescents, family therapy is recommended as an outpatient after
      hospitalization. CONCLUSION: In our country, the prevalence of anorexia nervosa
      is gradually increasing although we have not an idea concerning the frequency or
      prevalence of this disease which has serious and unpredictable complications. For
      what, it requires a multidisciplinary and prolonged surveillance to prevent
      recurrence.

PMID- 25775293
TI  - Triple complications due to spontaneous duodenal hematoma: hemorrhage, acute
      pancreatitis and cholestatic jaundice.

PMID- 25775294
TI  - [Retro-orbital mucormycosis and tuberculosis: a train may hide another].

PMID- 25775295
TI  - [Isolated hyperplastic gastric polyposis. A case report].

PMID- 25775296
TI  - [Diffuse interstitial pneumonia revealing systemic sclerosis sine scleroderma].

PMID- 25775297
TI  - [Pediatric rhabdoid tumors].

PMID- 25775298
TI  - [Exophthalmos revealing a carotid-cavernous fistula: about 2 cases].

PMID- 25775299
TI  - [Horner's syndrome following internal jugular vein catheterization in an infant].

PMID- 25775300
TI  - [Seminoma with cryptorchidism revealed by a giant abdominopelvic mass].

PMID- 25775301
TI  - [Haemophagocytic lymphohistiocytosis syndrome - related to severe malaria: rare
      association].

PMID- 25775311
TI  - War on Drugs Policing and Police Brutality.
AB  - BACKGROUND: War on Drugs policing has failed to reduce domestic street-level drug
      activity: the cost of drugs remains low and drugs remain widely available.
      OBJECTIVES: In light of growing attention to police brutality in the United
      States, this paper explores interconnections between specific War on Drugs
      policing strategies and police-related violence against Black adolescents and
      adults in the United States. METHODS: This paper reviews literature about (1)
      historical connections between race/ethnicity and policing in the United States;
      (2) the ways that the War on Drugs eroded specific legal protections originally
      designed to curtail police powers; and (3) the implications of these erosions for
      police brutality targeting Black communities. RESULTS: Policing and racism have
      been mutually constitutive in the United States. Erosions to the 4th Amendment to
      the Constitution and to the Posse Comitatus Act set the foundations for two War
      on Drugs policing strategies: stop and frisk and Special Weapons and Tactics
      (SWAT) teams. These strategies have created specific conditions conducive to
      police brutality targeting Black communities. Conclusions/Importance: War on
      Drugs policing strategies appear to increase police brutality targeting Black
      communities, even as they make little progress in reducing street-level drug
      activity. Several jurisdictions are retreating from the War on Drugs; this
      retreat should include restoring rights originally protected by the 4th Amendment
      and Posse Comitatus. While these legal changes occur, police chiefs should
      discontinue the use of SWAT teams to deal with low-level nonviolent drug offenses
      and should direct officers to cease engaging in stop and frisk.

PMID- 25775312
TI  - Cost-effectiveness and budget impact of hepatitis C virus treatment with
      sofosbuvir and ledipasvir in the United States.
AB  - BACKGROUND: Sofosbuvir and ledipasvir, which have recently been approved for
      treatment of chronic hepatitis C virus (HCV) infection, are more efficacious and
      safer than the old standard of care (oSOC) but are substantially more expensive.
      Whether and in which patients their improved efficacy justifies their increased
      cost is unclear. OBJECTIVE: To evaluate the cost-effectiveness and budget impact
      of sofosbuvir and ledipasvir. DESIGN: Microsimulation model of the natural
      history of HCV infection. DATA SOURCES: Published literature. TARGET POPULATION:
      Treatment-naive and treatment-experienced HCV population defined on the basis of
      HCV genotype, age, and fibrosis distribution in the United States. TIME HORIZON:
      Lifetime. PERSPECTIVE: Third-party payer. INTERVENTION: Simulation of sofosbuvir
      ledipasvir compared with the oSOC (interferon-based therapies). OUTCOME MEASURES:
      Quality-adjusted life-years (QALYs), incremental cost-effectiveness ratios
      (ICERs), and 5-year spending on antiviral drugs. RESULTS OF BASE-CASE ANALYSIS:
      Sofosbuvir-based therapies added 0.56 QALY relative to the oSOC at an ICER of $55
      400 per additional QALY. The ICERs ranged from $9700 to $284 300 per QALY
      depending on the patient's status with respect to treatment history, HCV
      genotype, and presence of cirrhosis. At a willingness-to-pay threshold of $100
      000 per QALY, sofosbuvir-based therapies were cost-effective in 83% of treatment
      naive and 81% of treatment-experienced patients. Compared with the oSOC, treating
      eligible HCV-infected persons in the United States with the new drugs would cost
      an additional $65 billion in the next 5 years, whereas the resulting cost offsets
      would be $16 billion. RESULTS OF SENSITIVITY ANALYSIS: Results were sensitive to
      drug price, drug efficacy, and quality of life after successful treatment.
      LIMITATION: Data on real-world effectiveness of new antivirals are lacking.
      CONCLUSION: Treatment of HCV is cost-effective in most patients, but additional
      resources and value-based patient prioritization are needed to manage patients
      with HCV. PRIMARY FUNDING SOURCE: National Institutes of Health.

PMID- 25775313
TI  - Cost-effectiveness of novel regimens for the treatment of hepatitis C virus.
AB  - BACKGROUND: New regimens for hepatitis C virus (HCV) have shorter treatment
      durations and increased rates of sustained virologic response compared with
      existing therapies but are extremely expensive. OBJECTIVE: To evaluate the cost
      effectiveness of these treatments under different assumptions about their price
      and efficacy. DESIGN: Discrete-event simulation. DATA SOURCES: Published
      literature. TARGET POPULATION: Treatment-naive patients infected with chronic HCV
      genotype 1, 2, or 3. TIME HORIZON: Lifetime. PERSPECTIVE: Societal. INTERVENTION:
      Usual care (boceprevir-ribavirin-pegylated interferon [PEG]) was compared with
      sofosbuvir-ribavirin-PEG and 3 PEG-free regimens: sofosbuvir-simeprevir,
      sofosbuvir-daclatasvir, and sofosbuvir-ledipasvir. For genotypes 2 and 3, usual
      care (ribavirin-PEG) was compared with sofosbuvir-ribavirin, sofosbuvir
      daclatasvir, and sofosbuvir-ledipasvir-ribavirin (genotype 3 only). OUTCOME
      MEASURES: Discounted costs (in 2014 U.S. dollars), quality-adjusted life-years
      (QALYs), and incremental cost-effectiveness ratios. RESULTS OF BASE-CASE
      ANALYSIS: Assuming sofosbuvir, simeprevir, daclatasvir, and ledipasvir cost
      $7000, $5500, $5500, and $875 per week, respectively, sofosbuvir-ledipasvir was
      cost-effective for genotype 1 and cost $12 825 more per QALY than usual care. For
      genotype 2, sofosbuvir-ribavirin and sofosbuvir-daclatasvir cost $110 000 and
      $691 000 per QALY, respectively. For genotype 3, sofosbuvir-ledipasvir-ribavirin
      cost $73 000 per QALY, sofosbuvir-ribavirin was more costly and less effective
      than usual care, and sofosbuvir-daclatasvir cost more than $396 000 per QALY at
      assumed prices. RESULTS OF SENSITIVITY ANALYSIS: Sofosbuvir-ledipasvir was the
      optimal strategy in most simulations for genotype 1 and would be cost-saving if
      sofosbuvir cost less than $5500. For genotype 2, sofosbuvir-ribavirin-PEG would
      be cost-saving if sofosbuvir cost less than $2250 per week. For genotype 3,
      sofosbuvir-ledipasvir-ribavirin would be cost-saving if sofosbuvir cost less than
      $1500 per week. LIMITATION: Data are lacking on real-world effectiveness of new
      treatments and some prices. CONCLUSION: From a societal perspective, novel
      treatments for HCV are cost-effective compared with usual care for genotype 1 and
      probably genotype 3 but not for genotype 2. PRIMARY FUNDING SOURCE: CVS Health.

PMID- 25775314
TI  - Effect of a culture-based screening algorithm on tuberculosis incidence in
      immigrants and refugees bound for the United States: a population-based cross
      sectional study.
AB  - BACKGROUND: Before 2007, immigrants and refugees bound for the United States were
      screened for tuberculosis (TB) by a smear-based algorithm that could not diagnose
      smear-negative/culture-positive TB. In 2007, the Centers for Disease Control and
      Prevention implemented a culture-based algorithm. OBJECTIVE: To evaluate the
      effect of the culture-based algorithm on preventing the importation of TB to the
      United States by immigrants and refugees from foreign countries. DESIGN:
      Population-based, cross-sectional study. SETTING: Panel physician sites for
      overseas medical examination. PATIENTS: Immigrants and refugees with TB.
      MEASUREMENTS: Comparison of the increase of smear-negative/culture-positive TB
      cases diagnosed overseas among immigrants and refugees by the culture-based
      algorithm with the decline of reported cases among foreign-born persons within 1
      year after arrival in the United States from 2007 to 2012. RESULTS: Of the 3 212
      421 arrivals of immigrants and refugees from 2007 to 2012, a total of 1 650 961
      (51.4%) were screened by the smear-based algorithm and 1 561 460 (48.6%) were
      screened by the culture-based algorithm. Among the 4032 TB cases diagnosed by the
      culture-based algorithm, 2195 (54.4%) were smear-negative/culture-positive.
      Before implementation (2002 to 2006), the annual number of reported cases among
      foreign-born persons within 1 year after arrival was relatively constant (range,
      1424 to 1626 cases; mean, 1504 cases) but decreased from 1511 to 940 cases during
      implementation (2007 to 2012). During the same period, the annual number of smear
      negative/culture-positive TB cases diagnosed overseas among immigrants and
      refugees bound for the United States by the culture-based algorithm increased
      from 4 to 629. LIMITATION: This analysis did not control for the decline in new
      arrivals of nonimmigrant visitors to the United States and the decrease of
      incidence of TB in their countries of origin. CONCLUSION: Implementation of the
      culture-based algorithm may have substantially reduced the incidence of TB among
      newly arrived, foreign-born persons in the United States. PRIMARY FUNDING SOURCE:
      None.

PMID- 25775316
TI  - Cervical spine clearance in obtunded patients after blunt traumatic injury: a
      systematic review.
AB  - BACKGROUND: Cervical spine clearance protocols are controversial for unconscious
      patients after blunt traumatic injury and negative findings on computed
      tomography (CT). PURPOSE: To review evidence about the utility of different
      cervical spine clearance protocols in excluding significant cervical spine injury
      after negative CT results in obtunded adults with blunt traumatic injury. DATA
      SOURCES: MEDLINE, EMBASE, CINAHL, Google Scholar, and the Cochrane Library were
      searched from January 2000 through November 2014. STUDY SELECTION: English
      language studies that examined patients with negative CT results having
      confirmatory routine testing with magnetic resonance imaging (MRI), dynamic
      radiography, or clinical examination and that reported outcome measures of missed
      cervical spine injury, need for operative stabilization, or prolonged use of
      cervical collars. DATA EXTRACTION: Independent reviewers evaluated the quality of
      studies and abstracted the data according to a predefined protocol. DATA
      SYNTHESIS: Of 28 observational studies (3627 patients) that met eligibility
      criteria, 7 were prospective studies (1686 patients) with low risk of bias and
      well-interpreted, high-quality CT scans. These 7 studies showed that 0% of
      significant injuries were missed after negative CT results. The overall studies
      using confirmatory routine testing with MRI showed incidence rates of 0% to 1.5%
      for cervical spine instability (16 studies; 1799 patients), 0% to 7.3% for need
      for operative fixation (17 studies; 1555 patients), and 0% to 29.5% for prolonged
      collar use (16 studies; 1453 patients). LIMITATIONS: Most studies were
      retrospective. Approaches to management of soft tissue changes with collars
      varied markedly. CONCLUSION: Cervical spine clearance in obtunded adults after
      blunt traumatic injury with negative results from a well-interpreted, high
      quality CT scan is probably a safe and efficient practice. PRIMARY FUNDING
      SOURCE: None.

PMID- 25775317
TI  - Cardiac screening with electrocardiography, stress echocardiography, or
      myocardial perfusion imaging: advice for high-value care from the American
      College of Physicians.
AB  - BACKGROUND: Cardiac screening in adults with resting or stress
      electrocardiography, stress echocardiography, or myocardial perfusion imaging can
      reveal findings associated with increased risk for coronary heart disease events,
      but inappropriate cardiac testing of low-risk adults has been identified as an
      important area of overuse by several professional societies. METHODS: Narrative
      review based on published systematic reviews; guidelines; and articles on the
      yield, benefits, and harms of cardiac screening in low-risk adults. RESULTS:
      Cardiac screening has not been shown to improve patient outcomes. It is also
      associated with potential harms due to false-positive results because they can
      lead to subsequent, potentially unnecessary tests and procedures. Cardiac
      screening is likely to be particularly inefficient in adults at low risk for
      coronary heart disease given the low prevalence and predictive values of testing
      in this population and the low likelihood that positive findings will affect
      treatment decisions. In this patient population, clinicians should focus on
      strategies for mitigating cardiovascular risk by treating modifiable risk factors
      (such as smoking, diabetes, hypertension, hyperlipidemia, and overweight) and
      encouraging healthy levels of exercise. HIGH-VALUE CARE ADVICE: Clinicians should
      not screen for cardiac disease in asymptomatic, low-risk adults with resting or
      stress electrocardiography, stress echocardiography, or stress myocardial
      perfusion imaging.

PMID- 25775318
TI  - Acute myocardial infarction: what's in a name?

PMID- 25775319
TI  - Celebrating the ACP Centennial: from the Annals Archive.

PMID- 25775320
TI  - White flag.

PMID- 25775321
TI  - Diagnosis of obstructive sleep apnea in adults.

PMID- 25775322
TI  - Diagnosis of obstructive sleep apnea in adults.

PMID- 25775323
TI  - Diagnosis of obstructive sleep apnea in adults.

PMID- 25775324
TI  - Informed decision making about prostate cancer screening.

PMID- 25775325
TI  - Informed decision making about prostate cancer screening.

PMID- 25775326
TI  - Treatment of hepatitis C virus infection.

PMID- 25775327
TI  - Treatment of hepatitis C virus infection.

PMID- 25775328
TI  - Treatment of hepatitis C virus infection.

PMID- 25775329
TI  - Treatment of hepatitis C virus infection.

PMID- 25775330
TI  - Low-dose computed tomography screening for lung cancer.

PMID- 25775331
TI  - Low-dose computed tomography screening for lung cancer.

PMID- 25775332
TI  - Three nonnucleoside reverse transcriptase inhibitor-sparing antiretroviral
      regimens for treatment-naive volunteers infected with HIV-1.

PMID- 25775333
TI  - Three nonnucleoside reverse transcriptase inhibitor-sparing antiretroviral
      regimens for treatment-naive volunteers infected with HIV-1.

PMID- 25775334
TI  - Three nonnucleoside reverse transcriptase inhibitor-sparing antiretroviral
      regimens for treatment-naive volunteers infected with HIV-1.

PMID- 25775335
TI  - Mercury poisoning presenting as sporadic Creutzfeldt-Jakob disease: a case
      report.

PMID- 25775336
TI  - Correction: combination antifungal therapy for invasive aspergillosis.

PMID- 25775337
TI  - Correction: the benefits of detecting and treating mild hypertension.

PMID- 25775339
TI  - Summaries for patients. Cardiac screening with electrocardiography, stress
      echocardiography, or myocardial perfusion imaging.

PMID- 25775340
TI  - Web Exclusives. The consult guys--anticoagulation? Antiplatelet? What's the
      score?

PMID- 25775341
TI  - ACP journal club. Review: in benign paroxysmal positional vertigo, the Epley
      maneuver increases symptom resolution.

PMID- 25775342
TI  - ACP journal club. In rotator cuff tears, primary tendon repair was better than
      physiotherapy for some measures of function at 5 y.

PMID- 25775343
TI  - ACP journal club. In ulcerative colitis, current use of thiopurines was
      associated with nonmelanoma skin cancer.

PMID- 25775344
TI  - ACP journal club. Dalteparin was at least as effective as UFH for VTE prevention
      in critically ill patients, with similar costs.

PMID- 25775345
TI  - ACP journal club. Review: perioperative beta-blockers have variable effects on
      outcomes in cardiac and noncardiac surgery.

PMID- 25775346
TI  - ACP journal club. Review: beta-blockers do not reduce mortality in myocardial
      infarction in the reperfusion era.

PMID- 25775347
TI  - ACP journal club. Early goal-directed therapy did not reduce mortality more than
      usual care in early septic shock.

PMID- 25775348
TI  - ACP journal club. For preventing exacerbations of COPD, withdrawal of inhaled
      glucocorticoids was noninferior to continuation.

PMID- 25775349
TI  - ACP journal club. Review: systemic corticosteroids reduce treatment failure but
      increase hyperglycemia in COPD exacerbations.

PMID- 25775350
TI  - ACP journal club. Review: <= 7 and > 7 days of systemic corticosteroids do not
      differ for efficacy in COPD exacerbations.

PMID- 25775351
TI  - ACP journal club. Review: in diabetes with multivessel or left main CAD, PCI
      increases death/MI/stroke combo compared with CABG.

PMID- 25775352
TI  - ACP journal club. Dual antiplatelets for 30 mo after drug-eluting stents reduced
      stent thrombosis and CV and cerebrovascular events.

PMID- 25775354
TI  - Downregulation of beta-microglobulin to diminish T-lymphocyte lysis of non
      syngeneic cell sources of engineered heart tissue constructs.
AB  - The presence of non-autologous major histocompatibility complex class I (MHC-I)
      molecules on the surface of the grafted cells is one of the main reasons for
      their rejection in non-syngeneic hosts. We present a straightforward strategy to
      decrease the presence of MHC-I by shRNA inhibition of beta-2-microglobulin (B2M),
      a conservative light chain of MHC-I, on the surface of two main cell types that
      are used to engineer heart tissue constructs. Engineered heart tissue constructs
      can be generated by combining mouse WT19 fibroblasts and mouse embryonic stem
      cell-derived cardiac myocytes (mESC-CM). WT19 fibroblasts were stably transduced
      with an anti-B2M shRNA, which yielded a cell line with dramatically reduced B2M
      expression levels (16 +/- 11% of mock treated control cell line). Interferon
      gamma treatment increased the levels of B2M expression by >3-fold in both control
      and transduced fibroblasts; yet, B2M expression levels still remained very low in
      the transduced cells. When compared with their unmodified counterparts,
      transduced fibroblasts caused 5.7-fold lesser activation of cognate T-cells. B2M
      depletion in mESC-CM was achieved by 72 h transduction with anti-B2M shRNA
      lentiviral particles. Transduced mESC-CM exhibited regular beating and expressed
      classical cardiac markers. When compared with their unmodified counterparts,
      transduced mESC-CM caused 2.5-fold lesser activation of cognate T-cells. In vivo
      assessment of B2M downregulation was performed by analyzing the preferential
      survival of B2M-downregulated cells in the intraperitoneal cavity of allogeneic
      mice. Both B2M-downregulated fibroblasts and B2M-downregulated myocytes survived
      significantly better when compared to their unmodified counterparts (2.01 +/- 0.4
      and 5.07 +/- 1.6 fold increase in survival, respectively). In contrast, when
      modified WT19 fibroblasts were injected into the intraperitoneal cavity of
      syngeneic C57Bl/6 mice, no significant survival advantage was observed. Notably,
      the preferential survival of B2M-downregulated cells persisted in allogeneic
      hosts with normal levels of natural killer cells, although the effect was lesser
      in magnitude. Use of shRNA against beta-2-microglobulin offers a simple and
      effective approach to minimize immunogenicity of the main cellular components of
      cardiac tissue constructs in non-syngeneic recipients.

PMID- 25775353
TI  - Age, Sex, and APOE epsilon4 Effects on Memory, Brain Structure, and beta-Amyloid
      Across the Adult Life Span.
AB  - IMPORTANCE: Typical cognitive aging may be defined as age-associated changes in
      cognitive performance in individuals who remain free of dementia. Ideally, the
      full adult age spectrum should be included to assess brain imaging findings
      associated with typical aging. OBJECTIVE: To compare age, sex, and APOE epsilon4
      effects on memory, brain structure (adjusted hippocampal volume [HVa]), and
      amyloid positron emission tomography (PET) in cognitively normal individuals aged
      30 to 95 years old. DESIGN, SETTING, AND PARTICIPANTS: Cross-sectional
      observational study (March 2006 to October 2014) at an academic medical center.
      We studied 1246 cognitively normal individuals, including 1209 participants aged
      50 to 95 years old enrolled in a population-based study of cognitive aging and 37
      self-selected volunteers aged 30 to 49 years old. MAIN OUTCOMES AND MEASURES:
      Memory, HVa, and amyloid PET. RESULTS: Overall, memory worsened from age 30 years
      through the 90s. The HVa worsened gradually from age 30 years to the mid-60s and
      more steeply beyond that age. The median amyloid PET was low until age 70 years
      and increased thereafter. Memory was worse in men than in women overall (P <
      .001) and more specifically beyond age 40 years. The HVa was lower in men than in
      women overall (P < .001) and more specifically beyond age 60 years. There was no
      sex difference in amyloid PET at any age. Within each sex, memory performance and
      HVa were not different by APOE epsilon4 status at any age. From age 70 years
      onward, APOE epsilon4 carriers had significantly greater median amyloid PET than
      noncarriers. However, the ages at which 10% of the population were amyloid PET
      positive were 57 years for APOE epsilon4 carriers and 64 years for noncarriers.
      CONCLUSIONS AND RELEVANCE: Male sex is associated with worse memory and HVa among
      cognitively normal individuals, while APOE epsilon4 is not. In contrast, APOE
      epsilon4 is associated with greater amyloid PET (from age 70 years onward), while
      sex is not. Worsening memory and HVa occur at earlier ages than abnormal amyloid
      PET. Therefore, neuropathological processes other than beta-amyloidosis must
      underlie declines in brain structure and memory function in middle age. Our
      findings are consistent with a model of late-onset Alzheimer disease in which
      beta-amyloidosis arises in later life on a background of preexisting structural
      and cognitive decline that is associated with aging and not with beta-amyloid
      deposits.

PMID- 25775355
TI  - Proportionality: a valid alternative to correlation for relative data.
AB  - In the life sciences, many measurement methods yield only the relative abundances
      of different components in a sample. With such relative-or compositional-data,
      differential expression needs careful interpretation, and correlation-a
      statistical workhorse for analyzing pairwise relationships-is an inappropriate
      measure of association. Using yeast gene expression data we show how correlation
      can be misleading and present proportionality as a valid alternative for relative
      data. We show how the strength of proportionality between two variables can be
      meaningfully and interpretably described by a new statistic phi which can be used
      instead of correlation as the basis of familiar analyses and visualisation
      methods, including co-expression networks and clustered heatmaps. While the main
      aim of this study is to present proportionality as a means to analyse relative
      data, it also raises intriguing questions about the molecular mechanisms
      underlying the proportional regulation of a range of yeast genes. 

PMID- 25775356
TI  - Zinc prevents sickness behavior induced by lipopolysaccharides after a stress
      challenge in rats.
AB  - Sickness behavior is considered part of the specific beneficial adaptive
      behavioral and neuroimmune changes that occur in individuals in response to
      infectious/inflammatory processes. However, in dangerous and stressful
      situations, sickness behavior should be momentarily abrogated to prioritize
      survival behaviors, such as fight or flight. Taking this assumption into account,
      we experimentally induced sickness behavior in rats using lipopolysaccharides
      (LPS), an endotoxin that mimics infection by gram-negative bacteria, and then
      exposed these rats to a restraint stress challenge. Zinc has been shown to play a
      regulatory role in the immune and nervous systems. Therefore, the objective of
      this study was to examine the effects of zinc treatment on the sickness response
      of stress-challenged rats. We evaluated 22-kHz ultrasonic vocalizations, open
      field behavior, tumor necrosis factor alpha (TNF-alpha), corticosterone, and
      brain-derived neurotrophic factor (BDNF) plasma levels. LPS administration
      induced sickness behavior in rats compared to controls, i.e., decreases in the
      distance traveled, average velocity, rearing frequency, self-grooming, and number
      of vocalizations, as well as an increase in the plasma levels of TNF-alpha,
      compared with controls after a stressor challenge. LPS also decreased BDNF
      expression but did not influence anxiety parameters. Zinc treatment was able to
      prevent sickness behavior in LPS-exposed rats after the stress challenge,
      restoring exploratory/motor behaviors, communication, and TNF-alpha levels
      similar to those of the control group. Thus, zinc treatment appears to be
      beneficial for sick animals when they are facing risky/stressful situations. 

PMID- 25775357
TI  - Are migraine and tension-type headache diagnostic types or points on a severity
      continuum? An exploration of the latent taxometric structure of headache.
AB  - The objective of this study was to assess whether migraine and tension-type
      headache (TTH) are best viewed as discrete entities or points on a severity
      continuum using taxometric analysis. Historically, classification systems have
      conceptualized the primary headache disorders of migraine and TTH as
      fundamentally different disorders that are differentiated by their characteristic
      symptom profiles and, as such, imply differing pathophysiologies and required
      treatments. Despite this categorical nosology, findings continue to emerge
      suggesting that migraine and TTH instead reflect dimensions of severity within
      the same headache construct. However, few studies have assessed this issue using
      taxometric statistical analyses or investigated how this taxonomic structure
      varies as a function of age and headache frequency. We conducted a latent-mode
      factor analysis of headache symptomatology obtained from 3449 individuals with
      headache from 2 previous, large-scale cross-sectional studies of primary headache
      sufferers (Martin et al., 2005, and Smitherman and Kolivas, 2013). Stratified
      taxometric analyses suggest that the validity of a categorical vs dimensional
      classification varies as a function of sample characteristics. Specifically,
      graphical results revealed that high headache frequency (>15 d/mo) and younger
      age (<24 years old) were associated with unimodal distributions suggestive of a
      dimensional construct of primary headache, whereas lower headache frequency and
      older age were associated with bimodal distributions characteristic of discrete
      diagnostic entities. Conceptualizing primary headache as a severity continuum was
      supported for young adults and those with frequent headaches. The distinctions of
      a categorical classification system were supported for adults (>24 years old) and
      those with infrequent headache. 

PMID- 25775359
TI  - Interleukin-6-mediated functional upregulation of TRPV1 receptors in dorsal root
      ganglion neurons through the activation of JAK/PI3K signaling pathway: roles in
      the development of bone cancer pain in a rat model.
AB  - Primary and metastatic cancers that affect bone are frequently associated with
      severe and intractable pain. The mechanisms underlying the pathogenesis of bone
      cancer pain still remain largely unknown. Previously, we have reported that
      sensitization of primary sensory dorsal root ganglion (DRG) neurons contributes
      to the pathogenesis of bone cancer pain in rats. In addition, numerous
      preclinical and clinical studies have revealed the pathological roles of
      interleukin-6 (IL-6) in inflammatory and neuropathic hyperalgesia. In this study,
      we investigated the role and the underlying mechanisms of IL-6 in the development
      of bone cancer pain using in vitro and in vivo approaches. We first demonstrated
      that elevated IL-6 in DRG neurons plays a vital role in the development of
      nociceptor sensitization and bone cancer-induced pain in a rat model through IL
      6/soluble IL-6 receptor (sIL-6R) trans-signaling. Moreover, we revealed that
      functional upregulation of transient receptor potential vanilloid channel type 1
      (TRPV1) in DRG neurons through the activation of Janus kinase
      (JAK)/phosphatidylinositol 3-kinase (PI3K) signaling pathway contributes to the
      effects of IL-6 on the pathogenesis of bone cancer pain. Therefore, suppression
      of functional upregulation of TRPV1 in DRG neurons by the inhibition of JAK/PI3K
      pathway, either before surgery or after surgery, reduces the hyperexcitability of
      DRG neurons and pain hyperalgesia in bone cancer rats. We here disclose a novel
      intracellular pathway, the IL-6/JAK/PI3K/TRPV1 signaling cascade, which may
      underlie the development of peripheral sensitization and bone cancer-induced
      pain. 

PMID- 25775358
TI  - Female migraineurs show lack of insular thinning with age.
AB  - Gray matter loss in cortical regions is a normal ageing process for the healthy
      brain. There have been few studies on the process of ageing of the brain in
      chronic neurological disorders. In this study, we evaluated changes in the
      cortical thickness by age in 92 female subjects (46 patients with migraine and 46
      healthy controls) using high-field magnetic resonance imaging. The results
      indicate that in contrast to healthy subjects, migraineurs show a lack of
      thinning in the insula by age. The functional significance of the lack of
      thinning is unknown, but it may contribute to the overall cortical
      hyperexcitability of the migraine brain because the region is tightly involved in
      a number of major brain networks involved in interoception, salience,
      nociception, and autonomic function, including the default mode network. 

PMID- 25775360
TI  - Pain-avoidance versus reward-seeking: an experimental investigation.
AB  - According to fear-avoidance models, a catastrophic interpretation of a painful
      experience may give rise to pain-related fear and avoidance, leading to the
      development and maintenance of chronic pain problems in the long term. However,
      little is known about how exactly motivation and goal prioritization play a role
      in the development of pain-related fear. This study investigates these processes
      in healthy volunteers using an experimental context with multiple, competing
      goals. In a differential human fear-conditioning paradigm, 57 participants
      performed joystick movements. In the control condition, one movement (conditioned
      stimulus; CS) was followed by a painful electrocutaneous unconditioned stimulus
      (pain-US) in 50% of the trials, whereas another movement (nonreinforced
      conditioned stimulus; CS) was not. In the experimental condition, a reward in the
      form of lottery tickets (reward-US) accompanied the presentation of the pain-US.
      Participants were classified into 3 groups, as a function of the goal, they
      reported to be the most important: (1) pain-avoidance, (2) reward-seeking, and
      (3) both goals being equally important. Results indicated that neither the reward
      co-occurring with pain nor the prioritized goal modulated pain-related fear.
      However, during subsequent choice trials, participants selected the painful
      movement more often when the reward was presented compared with the context in
      which the reward was absent. The latter effect was dependent on goal
      prioritization, with more frequent selections in the reward-seeking group, and
      the least selections in the pain-avoidance group. Taken together, these results
      underscore the importance of competing goals and goal prioritization in the
      attenuation of avoidance behavior. 

PMID- 25775361
TI  - Admixture and genetic diversity distribution patterns of non-recombining lineages
      of Native American ancestry in Colombian populations.
AB  - Genetic diversity of present American populations results from very complex
      demographic events involving different types and degrees of admixture. Through
      the analysis of lineage markers such as mtDNA and Y chromosome it is possible to
      recover the original Native American haplotypes, which remained identical since
      the admixture events due to the absence of recombination. However, the decrease
      in the effective population sizes and the consequent genetic drift effects
      suffered by these populations during the European colonization resulted in the
      loss or under-representation of a substantial fraction of the Native American
      lineages. In this study, we aim to clarify how the diversity and distribution of
      uniparental lineages vary with the different demographic characteristics (size,
      degree of isolation) and the different levels of admixture of extant Native
      groups in Colombia. We present new data resulting from the analyses of mtDNA
      whole control region, Y chromosome SNP haplogroups and STR haplotypes, and
      autosomal ancestry informative insertion-deletion polymorphisms in Colombian
      individuals from different ethnic and linguistic groups. The results demonstrate
      that populations presenting a high proportion of non-Native American ancestry
      have preserved nevertheless a substantial diversity of Native American lineages,
      for both mtDNA and Y chromosome. We suggest that, by maintaining the effective
      population sizes high, admixture allowed for a decrease in the effects of genetic
      drift due to Native population size reduction and thus resulting in an effective
      preservation of the Native American non-recombining lineages. 

PMID- 25775362
TI  - Complications and outcomes of primary phacotrabeculectomy with mitomycin C in a
      multi-ethnic asian population.
AB  - PURPOSE: To determine the occurrence of intraoperative and postoperative
      complications up to three years after primary phacotrabeculectomy with
      intraoperative use of Mitomycin C (MMC) in primary open angle (POAG) and primary
      angle closure glaucoma (PACG) patients, and the effect of postoperative
      complications on surgical outcome. METHODS: Retrospective review of 160
      consecutive patients with POAG (n = 105) and PACG (n = 55), who underwent primary
      phacotrabeculectomy with MMC at the National University Hospital, Singapore, from
      January 1, 2008 to December 31, 2010. Data was collected using a standardized
      form that included patient demographic information, ocular characteristics and
      postoperative complications, including hypotony (defined as intraocular pressure
      < 6 mmHg), shallow anterior chamber (AC) and hyphema. RESULTS: The mean age +/-
      standard deviation (SD) of patients was 68.2 +/- 8.2 years. No patient lost light
      perception during duration of follow-up. 77% of the postoperative complications
      occurred within the first month only. The commonest complications were hypotony
      (n = 41, 25.6%), hyphema (n = 16, 10.0%) and shallow AC (n = 16, 10.0%). Five
      patients (3.1%) required reoperation for their complications. Early hypotony
      (defined as hypotony < 30 days postoperatively) was an independent risk factor
      for surgical failure (hazard ratio [HR], 5.1; 95% CI, 1.6-16.2; p = 0.01).
      Hypotony with another complication was also a risk factor for surgical failure (p
      < 0.02). CONCLUSIONS: Hypotony, hyphema and shallow AC were the commonest
      postoperative complications in POAG and PACG patients after phacotrabeculectomy
      with MMC. Most complications were transient and self-limiting. Early hypotony
      within the first month was a significant risk factor for surgical failure.

PMID- 25775364
TI  - Increasing plantarflexion angle during landing reduces vertical ground reaction
      forces, loading rates and the hip's contribution to support moment within
      participants.
AB  - The ankle joint's role in shock absorption during landing has been researched in
      many studies, which have found that landing with higher amounts of plantarflexion
      (PF) results in lower peak vertical ground reaction forces and loading rates.
      However, there has not yet been a study that compares drop landings within
      participants along a quantitative continuum of PF angles. Using a custom-written
      real-time feedback program, participants adjusted their ankles to an instructed
      PF angle and dropped onto two force platforms. For increasing PF, peak ground
      reaction force and peak loading rate during weight acceptance decreased
      significantly. The hip's contribution to peak support moment decreased as PF at
      initial contact increased up to 30 degrees . The ankle and knee contributions
      increased over this same continuum of PF angles. There appears to be no optimal
      PF angle based on peak ground reaction force and loading rate measurements, but
      there may be an optimum where joint contributions to peak support moment converge
      and the hip moment's contribution is minimised. 

PMID- 25775363
TI  - Population genetic history of Aristeus antennatus (Crustacea: Decapoda) in the
      Western and Central Mediterranean Sea.
AB  - Aristeus antennatus is an ecologically and economically important deep-water
      species in the Mediterranean Sea. In this study we investigated the genetic
      variability of A. antennatus sampled from 10 sampling stations in the Western and
      Central Mediterranean. By comparing our new samples with available data from the
      Western area, we aim to identify potential genetic stocks of A. antennatus and to
      reconstruct its historical demography in the Mediterranean. We analyzed two
      regions of mitochondrial DNA in 319 individuals, namely COI and 16S. We found two
      main results: i) the genetic diversity values consistent with previous data
      within the Mediterranean and the absence of barriers to gene flow within the
      Mediterranean Sea; ii) a constant long-term effective population size in almost
      all demes but a strong signature of population expansion in the pooled sample
      about 50,000 years B.P./ago. We propose two explanation for our results. The
      first is based on the ecology of A. antennatus. We suggest the existence of a
      complex meta-population structured into two layers: a deeper-dwelling stock, not
      affected by fishing, which preserves the pattern of historical demography; and
      genetically homogeneous demes inhabiting the fishing grounds. The larval
      dispersal, adult migration and continuous movements of individuals from "virgin"
      deeper grounds not affected by fishing to upper fishing areas support an
      effective 'rescue effect' contributing to the recovery of the exploited stocks
      and explain their genetic homogeneity throughout the Mediterranean Sea. The
      second is based on the reproduction model of this shrimp: the high variance in
      offspring production calls for a careful interpretation of the data observed
      under classical population genetics and Kingman's coalescent. In both cases,
      management policies for A. antennatus will therefore require careful evaluation
      of the meta-population dynamics of all stocks in the Mediterranean. In the
      future, it will be particularly relevant to sample the deepest ones directly. 

PMID- 25775365
TI  - Functional outcomes of partial prostate ablation and focal therapy: are we
      managing expectations of a bar set too high?
AB  - PURPOSE OF REVIEW: Prostate ablation treatments have long been utilized although
      a recent shift away from whole gland ablation has occurred in an effort to
      decrease side-effects. Interest in this form of focal treatment has developed
      following encouraging initial reports suggesting feasibility, safety and
      favorable quality of life. Data on functional outcomes and limitations are now
      accumulating that require careful interpretation for educating patients and
      providers on the realistic outcomes achievable with these approaches. RECENT
      FINDINGS: Published results of partial prostate ablation provide short-term
      outcomes using a variety of metrics to estimate treatment effects on identified
      cancerous regions of the prostate. Validations of these metrics in regard to
      intermediate and long-term oncologic outcomes are awaited. Functional results
      indicate short-term effects on urinary and sexual function are frequent although
      perhaps less severe than whole gland or conventional treatments. SUMMARY: Outcome
      measures from prostate ablation have served to partially address some patient
      short-term goals of treatment and to support the further development of these
      approaches. More specific data to understand the long-term outcomes, goals and
      expectations for functional recovery that may be specific to each treatment
      modality are needed.

PMID- 25775366
TI  - Focal therapy of prostate cancer: making steady progress toward a first-line
      image-guided treatment modality.

PMID- 25775367
TI  - Polymeric nanomedicine for tumor-targeted combination therapy to elicit
      synergistic genotoxicity against prostate cancer.
AB  - To improve the therapeutic efficacy of anticancer combination therapy, we
      designed a nanoplatform based on N-(2-hydroxypropyl) methacrylamide (HPMA)
      copolymers that allows covalent bonding of two chemotherapeutics acting via
      different anticancer mechanisms and that can enter target cells by receptor
      mediated endocytosis. Doxorubicin (DOX) was covalently conjugated to a nanosized
      HPMA copolymer using a pH-sensitive hydrazone bond and 5-fluorouracil (5-Fu) was
      conjugated to the same backbone using an enzymatically degradable oligopeptide
      Gly-Phe-Leu-Gly sequence. Then, the conjugate was decorated with galectin-3
      targeting peptide G3-C12 [P-(G3-C12)-DOX-Fu]. The two drugs showed similar in
      vitro release profiles, suggesting that they may be able to work synergistically
      in the codelivery system. In galectin-3 overexpressed PC-3 human prostate
      carcinoma cells, P-(G3-C12)-DOX-Fu surprisingly exhibited comparable cytotoxicity
      to free DOX at high concentration by increasing cell internalization and exerting
      synergistic genotoxic effects of cell cycle arrest, caspase-3 activation, and DNA
      damage. In mice bearing PC-3 tumor xenografts, the use of tumor-targeting ligand
      substantially enhanced the intracellular delivery of P-(G3-C12)-DOX-Fu in tumors.
      The targeted dual drug-loaded conjugate inhibited tumor growth to a greater
      extent (tumor inhibition of 81.6%) than did nontargeted P-DOX-Fu (71.2%), P-DOX
      (63%), DOX.HCl (40.5%), P-Fu (32.0%), or 5-Fu (14.6%), without inducing any
      obvious side effects. These results demonstrate the potential of synergistic
      combination therapy using targeted nanocarriers for efficient treatment of
      prostate cancer. 

PMID- 25775368
TI  - Spin-orbit TDDFT electronic structure of diplatinum(II,II) complexes.
AB  - [Pt2(MU-P2O5H2)4](4-) (Pt(pop)) and its perfluoroborated derivative [Pt2(MU
      P2O5(BF2)2)4](4-) (Pt(pop-BF2)) are d(8)-d(8) complexes whose electronic excited
      states can drive reductions and oxidations of relatively inert substrates. We
      performed spin-orbit (SO) TDDFT calculations on these complexes that account for
      their absorption spectra across the entire UV-vis spectral region. The complexes
      exhibit both fluorescence and phosphorescence attributable, respectively, to
      singlet and triplet excited states of dsigma*psigma origin. These features are
      energetically isolated from each other (~7000 cm(-1) for (Pt(pop-BF2)) as well as
      from higher-lying states (5800 cm(-1)). The lowest (3)dsigma*psigma state is
      split into three SO states by interactions with higher-lying singlet states with
      dpipsigma and, to a lesser extent, ppipsigma contributions. The spectroscopically
      allowed dsigma*psigma SO state has ~96% singlet character with small admixtures
      of higher triplets of partial dpipsigma and ppipsigma characters that also mix
      with (3)dsigma*psigma, resulting in a second-order (1)dsigma*psigma
      (3)dsigma*psigma SO interaction that facilitates intersystem crossing (ISC). All
      SO interactions involving the dsigma*psigma states are weak because of large
      energy gaps to higher interacting states. The spectroscopically allowed
      dsigma*psigma SO state is followed by a dense manifold of ligand-to-metal-metal
      charge transfer states, some with ppipsigma (at lower energies) or dpipsigma
      contributions (at higher energies). Spectroscopically active higher states are
      strongly spin-mixed. The electronic structure, state ordering, and relative
      energies are minimally perturbed when the calculation is performed at the
      optimized geometries of the (1)dsigma*psigma and (3)dsigma*psigma excited states
      (rather than the ground state). Results obtained for Pt(pop) are very similar,
      showing slightly smaller energy gaps and, possibly, an additional
      (1)dsigma*psigma - (3)dsigma*psigma second order SO interaction involving higher
      (1)dpipsigma* states that could account in part for the much faster ISC. It also
      appears that (1)dsigma*psigma -> (3)dsigma*psigma ISC requires a structural
      distortion that has a lower barrier for Pt(pop) than for the more rigid Pt(pop
      BF2). 

PMID- 25775369
TI  - Social surrogacy and adjustment: exploring the correlates of having a "social
      helper" for shy and non-shy young adolescents.
AB  - A social surrogate is an individual who offers help and comfort in social
      situations or makes social events more exciting. In this study of 157 young
      adolescents (55% female; Mage = 13.84 years, SD = 0.75 years), the authors
      examined whether the linear and curvilinear associations between self-reported
      social surrogate use and adjustment outcomes (social problems, loneliness,
      anxiety symptoms, depressive symptoms) varied as a function of shyness and
      gender, after accounting for the effects of positive friendship quality.
      Regression analyses revealed that low and high levels of social surrogate use
      were related to greater social problems for all adolescents. In addition, shyness
      emerged as a moderator for several curvilinear effects. Specifically, results
      indicated that (a) high levels of social surrogate use were associated with
      greater anxiety for adolescents high in shyness; and (b) low levels of social
      surrogate use were associated with greater depressive symptoms for adolescents
      low in shyness. Findings highlight the developmental importance of specific types
      of relationship experiences during early adolescence and point to different
      implications of social surrogate use for shy and non-shy young adolescents.

PMID- 25775370
TI  - Use of vinegar to relieve persistent hiccups in an advanced cancer patient.
AB  - BACKGROUND: This case report describes a patient whose persistent hiccups
      significantly improved with the use of vinegar. CASE PRESENTATION: A patient with
      an adenocarcinoma of the colon and hepatic metastases developed hiccups the day
      following chemotherapy with FOL-FOX (folinic acid (leucovorin), 5-fluorouracil,
      oxaliplatin). Hiccups continued for seven days with no improvement from a number
      of commonly used pharmacological agents (chlorpromazine, metoclopramide,
      haloperidol, and baclofen). Relief was finally obtained after sipping vinegar.
      CASE MANAGEMENT AND OUTCOME: Hiccups occurred several times during the following
      chemotherapy cycles but the patient completed the treatment using vinegar when
      they recurred without stopping any drugs. Hiccups stopped or decreased in
      intensity or in rate per minute after sipping vinegar. CONCLUSIONS: Hypotheses
      have been developed for the molecular and physiological mechanisms underlying
      sour compounds' effectiveness in relieving hiccups. Further studies should
      explore the potential role of vinegar in relieving hiccups in advanced heavily
      treated cancer patients.

PMID- 25775371
TI  - Too hot to sleep? Sleep behaviour and surface body temperature of Wahlberg's
      Epauletted Fruit Bat.
AB  - The significance of sleep and factors that affect it have been well documented,
      however, in light of global climate change the effect of temperature on sleep
      patterns has only recently gained attention. Unlike many mammals, bats (order:
      Chiroptera) are nocturnal and little is known about their sleep and the effects
      of ambient temperature (Ta) on their sleep. Consequently we investigated seasonal
      temperature effects on sleep behaviour and surface body temperature of free
      ranging Wahlberg's epauletted fruit bat, Epomophorus wahlbergi, at a tree roost.
      Sleep behaviours of E. wahlbergi were recorded, including: sleep duration and
      sleep incidences (i.e. one eye open and both eyes closed). Sleep differed
      significantly across all the individuals in terms of sleep duration and sleep
      incidences. Individuals generally spent more time awake than sleeping. The
      percentage of each day bats spent asleep was significantly higher during winter
      (27.6%), compared with summer (15.6%). In summer, 20.7% of the sleeping bats used
      one eye open sleep, and this is possibly the first evidence of one-eye-sleep in
      non-marine mammals. Sleep duration decreased with extreme heat as bats spent
      significantly more time trying to cool by licking their fur, spreading their
      wings and panting. Skin temperatures of E. wahlbergi were significantly higher
      when Ta was >=35 degrees C and no bats slept at these high temperatures.
      Consequently extremely hot days negatively impact roosting fruit bats, as they
      were forced to be awake to cool themselves. This has implications for these bats
      given predicted climate change scenarios. 

PMID- 25775372
TI  - The Influence of Supervisory Neglect on Subtypes of Emerging Adult Substance Use
      After Controlling for Familial Factors, Relationship Status, and Individual
      Traits.
AB  - BACKGROUND: This study is the first to explore how child supervisory neglect
      influences patterns of substance use among young adults. This study investigated
      patterns of substance use among males and females, 18 to 24 years old, after
      controlling for adolescent parental drinking, living with parents, relationship
      status, delinquency, and depression. METHODS: The study sample (N=10,618)
      included individuals who participated in Waves I (1994-1995) and III (2001-2002)
      of the National Longitudinal Study of Adolescent Health (Add Health). The study
      used latent class analysis to ascertain how patterns of substance use emerged as
      distinct classes. RESULTS: For both males and females, we identified the
      following 4 classes of substance use: (1) heavy polysubstance use, (2) moderate
      polysubstance use, (3) alcohol and marijuana, and (4) low-use substance use
      patterns. Multinomial logistic regression indicated that, for both males and
      females 18 to 24 years old, experiencing supervisory neglect, being depressed,
      being single, and engaging in adolescent delinquency serve as risk factors for
      heavy polysubstance use class membership. Conversely, being black or Hispanic
      lowered the likelihood of polysubstance use for males and females. For females
      only, living with parents served as a protective factor that reduced the risk of
      membership in heavy polysubstance use, moderate polysubstance use, and alcohol
      and marijuana classes. For males only, being less educated increased the risk of
      heavy polysubstance use class membership. CONCLUSIONS: Results from this
      exploratory study underscore the enduring effect of supervisory neglect on
      substance use among male and female young adults. Future studies should explore
      whether these relationships hold over time.

PMID- 25775373
TI  - Investigations on human and animal remains from a medieval shaft well in
      Ayasuluk/Ephesos (Turkey).
AB  - In course of the archaeological survey of Ayasuluk/Ephesos region (Turkey), a
      shaft well situated at the area of an extensive medieval bathing complex was
      excavated. In the stratum corresponding to the reign Mehmed II the well-preserved
      skeletons of two humans, an equine and a canine were recovered. Anthropological
      analysis of the human skeletons indentified two males aged 22 (+/- 3) and 36 (+/-
      5) years. The skeleton of the younger individual showed signs of various
      antemortal conditions, including a well-healed fraction of right arc of the fifth
      lumbar vertebra, and a marked asymmetry of the shoulder joints. The older
      individual exhibited significant peri/postmortem injuries at the elbows, with
      evident signs of peeling and external burning. Also, the few elements of the
      cranium recovered showed also indications of burning. Archaeozoological
      characterization of the complete skeletons of the equine and canine established
      evidence of well cared-for animals of high value. The time of disposal of this
      group coincides with uprising of the formerly ruling Aydnoullar clan against the
      Ottomans in power. The human individuals recovered from the well may have been
      members of Aydnoullar tribe or men in service of the latter, suffering severe
      torture and/or mutilation for siding with the rebels after defeat. 

PMID- 25775374
TI  - Delphi survey of international pharmacology experts: an attempt to derive
      international recommendations for use of medicine in breastfeeding women.
AB  - INTRODUCTION: There are currently no common guidelines used by health
      professionals to aid decision-making around the use of medicines during
      breastfeeding. Several specialized books, Web sites, and drug information
      services exist; however, all use slightly different criteria to derive their
      "safety hierarchy." The aim of this study was to build consensus among
      international experts in pharmacology and breastfeeding to develop an agreed-upon
      classification system for safety of medicine use in breastfeeding women. STUDY
      METHOD: A three-round Web-based Delphi qualitative research design was used.
      RESULTS: Seventeen experts in pharmacy/pharmacology and breastfeeding identified
      15 key parameters that are used to inform decisions about medicines and
      breastfeeding. The most important parameters about the infant were the age and
      health of the child, and those of the medicine were the safety profile and
      experience of use in infants. The experts had a clear understanding of the
      complexity of decision-making when prescribing for breastfeeding women. Although
      the current number or letter classification systems do not incorporate important
      considerations such as infant age, a longer "descriptive text" incorporating all
      considerations may be impractical in busy clinical practice. CONCLUSIONS:
      Although clinicians and lay people would appreciate a simple classification
      scheme, in practice, decision-making about the safety of medicines for
      breastfeeding women is complex.

PMID- 25775375
TI  - Glycated hemoglobin and incident type 2 diabetes in singaporean chinese adults:
      the Singapore Chinese health study.
AB  - BACKGROUND: The American Diabetes Association recently included glycated
      hemoglobin in the diagnostic criteria for diabetes, but research on the utility
      of this biomarker in Southeast Asians is scant. The aim of this study was to
      evaluate the association between percent HbA1c and incident diabetes in an Asian
      population of adult men and women without reported diabetes. METHODS: Data
      analysis of 5,770 men and women enrolled in the Singapore Chinese Health Study
      who provided a blood sample at the follow-up I visit (1999-2004) and had no
      cancer and no reported history of diabetes or cardiovascular disease events.
      Diabetes was defined as self-report of physician diagnosis, identified at the
      follow-up II visit (2006-2010). RESULTS: Hazard ratios (and 95% confidence
      intervals) for incident diabetes by 5 categories of HbA1c were estimated with Cox
      regression models and continuous HbA1c with cubic spline analysis. Compared to
      individuals with an HbA1c <= 5.7% (<=39 mmol/mol), individuals with HbA1c 5.8
      5.9% (40-41 mmol/mol), 6.0-6.1% (42-43 mmol/mol), 6.2-6.4% (44-47 mmol/mol), and
      >= 6.5% (>=48 mmol/mol) had significantly increased risk for incident diabetes
      during follow-up. In cubic spline analysis, levels below 5.7% HbA1c were not
      significantly associated with incident diabetes. CONCLUSIONS: Our study found a
      strong and graded association with HbA1c 5.8% and above with incident diabetes in
      Chinese men and women.

PMID- 25775376
TI  - Position of the physician's nametag--a randomized, blinded trial.
AB  - BACKGROUND: The patient-physician relation begins when the physician introduces
      himself with name and function. Most institutions request a nametag with name and
      function to be worn. Although nametags are consequently worn, the optimal
      position for the nametag is unknown. It was the purpose of this study to identify
      whether positioning the nametag on the right or the left chest side provides
      better visibility to the patient. METHOD AND MATERIAL: One hundred volunteers,
      blinded to the experimental setup, presented for an orthopedic consultation in a
      standardized manner. The nametag of the physician was randomly positioned on the
      left chest side and presented to 50 individuals (age 35 years (range 17 to 83))
      or the right chest side and then presented to 50 other individuals (35 years
      (range 16 to 59)). The time of the participant noticing the nametag was
      documented. Subsequently, the participant was questioned concerning the relevance
      of a nametag and verbal self-introduction of the physician. RESULTS: 38% of the
      participants noticed the nametag on the right as opposed to 20% who noticed it if
      placed on the left upper chest (p = 0.0473). The mean time to detection was 9
      (range 1-40) seconds for nametags on the right and 25.2 seconds (range 3 to 49, p
      = 0.006) on the left. For 87% of the participants, a nametag is expected and
      important and nearly all participants (96%) expected the physician to introduce
      himself verbally. CONCLUSION: It is expected that a physician wears a nametag and
      introduce himself verbally at the first encounter. Positioning the nametag on the
      right chest side results in better and faster visibility.

PMID- 25775377
TI  - Ecotype evolution in Glossina palpalis subspecies, major vectors of sleeping
      sickness.
AB  - BACKGROUND: The role of environmental factors in driving adaptive trajectories of
      living organisms is still being debated. This is even more important to
      understand when dealing with important neglected diseases and their vectors.
      METHODOLOGY/PRINCIPAL FINDINGS: In this paper, we analysed genetic divergence,
      computed from seven microsatellite loci, of 614 tsetse flies (Glossina palpalis
      gambiensis and Glossina palpalis palpalis, major vectors of animal and human
      trypanosomes) from 28 sites of West and Central Africa. We found that the two
      subspecies are so divergent that they deserve the species status. Controlling for
      geographic and time distances that separate these samples, which have a
      significant effect, we found that G. p. gambiensis from different landscapes
      (Niayes of Senegal, savannah and coastal environments) were significantly
      genetically different and thus represent different ecotypes or subspecies. We
      also confirm that G. p. palpalis from Ivory Coast, Cameroon and DRC are strongly
      divergent. CONCLUSIONS/SIGNIFICANCE: These results provide an opportunity to
      examine whether new tsetse fly ecotypes might display different behaviour,
      dispersal patterns, host preferences and vectorial capacities. This work also
      urges a revision of taxonomic status of Glossina palpalis subspecies and
      highlights again how fast ecological divergence can be, especially in host
      parasite-vector systems.

PMID- 25775378
TI  - The effect of topical ethanol extract of Cotinus coggygria Scop. on cutaneous
      wound healing in rats.
AB  - The aim of this study is to determine the cutaneous wound healing effects of the
      ethanol extract of Cotinus coggygria leaves in rats by excision wound model to
      provide scientific evidence for the traditional use of C. coggygria Scop. The
      levels of malondialdehyde, catalase, superoxide dismutase, glutathione and
      hydroxyproline were investigated in wound tissues. Histopathological examination
      was also performed. The hydroxyproline content of the granulation tissue and the
      glutathione levels were both significantly higher in the treatment group than in
      the control group (p < 0.05 for both); while the malondialdehyde levels were
      significantly lower in the treatment group (p < 0.05). These results were
      supported with histological results. The ethanol extract of C. coggygria Scop
      could be considered as an effective agent in wound healing in accordance with its
      traditional use.

PMID- 25775379
TI  - Single-pill combination therapy for type 2 diabetes mellitus: linagliptin plus
      empagliflozin.
AB  - BACKGROUND: Treatment of type 2 diabetes mellitus invariably requires the use of
      multiple daily medications which can impact negatively on patient adherence. As a
      result, there is growing interest in the use of single-pill combinations that can
      reduce the pill burden. Many such formulations incorporate metformin, although
      this agent is not suitable for all patients. The single-pill combination of the
      dipeptidyl peptidase-4 inhibitor linagliptin with the sodium glucose co
      transporter 2 inhibitor empagliflozin offers a new and attractive option, given
      their complementary mechanisms of action. SCOPE: Publications with titles
      containing the keywords 'linagliptin' or 'empagliflozin' were identified from a
      non-systematic search of PubMed without date restrictions, together with
      abstracts presented at the annual meetings of the American Diabetes Association
      and the European Association for the Study of Diabetes 2012-2014.
      ClinicalTrials.gov was searched for entries containing these two keywords.
      Additional references known to the author were included. FINDINGS: The efficacy
      and safety of linagliptin and empagliflozin as monotherapy or in combination with
      other oral antidiabetic drugs has been established through extensive clinical
      trial programs. Studies specifically evaluating the efficacy/safety of a
      dipeptidyl peptidase-4 inhibitor/sodium glucose co-transporter 2 inhibitor in
      combination are limited, but do include two studies of linagliptin/empagliflozin
      of up to 52 weeks in duration. These studies show that the single-pill
      combination of linagliptin and empagliflozin produced clinical improvements in
      glycemic control that were generally superior to the improvements seen with
      linagliptin and empagliflozin alone, but with a safety profile comparable to that
      of the individual constituents. CONCLUSIONS: The single-pill combination of
      linagliptin and empagliflozin, with their complementary mechanisms of action, is
      a promising treatment option for patients with type 2 diabetes mellitus. It would
      reduce the daily pill burden in this population, potentially improving adherence
      to, and optimizing the benefits of, treatment of diabetes mellitus.

PMID- 25775380
TI  - Age-associated changes in granulosa cell transcript abundance in equine
      preovulatory follicles.
AB  - Age-related changes in follicle paracrine signalling are not defined, and
      follicular gene transcript abundance could predict oocyte viability. Granulosa
      cells from preovulatory follicles of mares considered Young (n=12; 4-14 years),
      Mid-aged (n=9; 15-19 years) and Old (n=14; 20-27 years) were evaluated for
      transcript abundance related to systemic and follicle-specific pathways. Gene
      transcript abundance for receptors of insulin, adiponectin and peroxisome
      proliferating factor-gamma were higher or tended to be higher in Mid-aged or Old
      than Young mares. Transcript abundance for interleukin (IL)-6 was elevated in Old
      versus Young mares, and IL-6 signal transducer was elevated in Old versus younger
      groups. Expression of tumour necrosis factor (TNF) receptor superfamily member 1A
      was higher in Mid-aged than Young mares, whereas TNF-inducible gene 6 protein
      mRNA tended to decrease in Mid-aged versus Young and Old mares. Genes for LH
      receptor and steroidogenic acute regulatory protein tended to be increased in Old
      versus Mid-aged and Young mares, respectively. Young and Old mares had higher
      mRNA for tissue-type plasminogen activator than Mid-aged mares. Thioredoxin-2
      mRNA was higher in Old than younger groups. We observed age-related changes in
      mRNA of receptors for metabolic hormones, inflammatory processes, steroidogenic
      hormones, tissue remodelling and mitochondrial function, which could contribute
      to and/or mark alterations in follicular function and fertility. 

PMID- 25775381
TI  - Erythrocytosis associated with hyperthyroidism: a rare case report and clinical
      study of possible mechanism.
AB  - PURPOSE: To report a rare case of erythrocytosis that occurred in close
      association with Graves' hyperthyroidism. In order to explore the role of altered
      erythropoiesis in hyperthyroidism, factors related to erythropoiesis were studied
      in 30 patients with Graves' hyperthyroidism. METHOD: The relationship between
      thyroid hormone level and erythrocytosis was studied in a patient with Graves'
      hyperthyroidism and erythrocytosis. Later, 30 consecutive patients with proven
      untreated Graves' hyperthyroidism and 30 age- and sex-matched healthy controls
      were recruited. All patients received methimazole therapy. Erythrocyte indices,
      thyroid function, serum erythropoietin (EPO), and hypoxia-inducible factor-1alpha
      (HIF-1alpha) concentrations were measured before and after eight weeks of
      therapy. RESULTS: In our case study, erythrocytosis relapsed with elevation of
      thyroid hormones. Methimazole or subsequent radioiodine therapy reduced the
      conditions of erythrocytosis and thyroid function returned to normal. In the
      clinical study, erythrocyte counts, serum erythropoietin, and HIF-1alpha levels
      in the hyperthyroid group were significantly higher than those in the control
      subjects. All subjects were grouped together for correlation analyses and HIF
      1alpha was shown to correlate with total triiodothyronine (TT(3)), total
      thyroxine (TT(4)), and EPO levels. The correlation between EPO and TT(3) or TT(4)
      approached significance. After eight weeks of anti-thyroid drug therapy, a small
      but statistically significant increase in hemoglobin and erythrocyte count with a
      significant decrease in HIF-1alpha and EPO level was seen in hyperthyroid
      subjects. CONCLUSION: Erythrocytosis may appear in patients with hyperthyroidism,
      and one possible mechanism is thyroid hormone-induced augmentation of HIF-1alpha,
      resulting in increased EPO levels.

PMID- 25775382
TI  - Imported "Evidence-Based" or Locally Grown Interventions: A False Dichotomy and
      Some Hard Choices in Implementation Science.
AB  - When public health programs are expanding to new areas or territories, it is
      often recommended by policy-makers and donors that existing evidence-based
      practices (EBPs) are to be adapted and implemented. While rationale behind this
      approach is understandable, proper adaptation to culturally different settings
      may be no less intensive than development of a new intervention based on the
      local context. A narrow understanding of implementation science concept may lead
      to overlooking valuable indigenous practices, which may be summarized into
      effective and potentially more sustainable models. This paper examines from
      practical standpoint the process and common caveats in cross-cultural adaptation
      of EPBs and argues for closer attention to available local experiences. 

PMID- 25775383
TI  - Line-tension effects on heterogeneous nucleation on a spherical substrate and in
      a spherical cavity.
AB  - The line-tension effects on heterogeneous nucleation are considered when a
      spherical lens-shaped nucleus is nucleated on top of a spherical substrate and on
      the bottom of the wall of a spherical cavity. The effect of line tension on the
      nucleation barrier can be separated from the usual volume term. As the radius of
      the substrate increases, the nucleation barrier decreases and approaches that of
      a flat substrate. However, as the radius of the cavity increases, the nucleation
      barrier increases and approaches that of a flat substrate. A small spherical
      substrate is a less active nucleation site than a flat substrate, and a small
      spherical cavity is a more active nucleation site than a flat substrate. In
      contrast, the line-tension effect on the nucleation barrier is maximum when the
      radii of the nucleus and the substrate or cavity become comparable. Therefore, by
      tuning the size of the spherical substrate or spherical cavity, the effect of the
      line tension can be optimized. These results will be useful in broad range of
      applications from material processing to understanding of global climate, where
      the heterogeneous nucleation plays a vital role. 

PMID- 25775384
TI  - Joint experimental and computational investigation of the structural and
      spectroscopic properties of poly(vinylidene fluoride) polymorphs.
AB  - State-of-the-art density functional theory calculations are here adopted for the
      investigation of the crystal structure and of the vibrational properties of
      alpha, beta, gamma, and delta phases of poly(vinylidene fluoride) (PVDF), in
      comparison with IR and Raman measurements. DFT calculations allowed a detailed
      interpretation of the IR and Raman spectra of alpha and beta phases, giving
      vibrational assignments useful for qualitative and quantitative characterization
      of these systems. From a molecular perspective, the computational investigation
      of the crystal structure and the spectra of PVDF polymorphs helped in clarifying
      the role of supramolecular dipole-dipole interactions, which indeed modulate the
      vibrational properties of these systems, indicating also that intermolecular
      interaction could play a significant role in the modulation of ferroelectric
      properties. Furthermore, the combined experimental and computational approach
      allowed us to identify and characterize the thermally and mechanically induced
      gamma phase, shedding light on the far-IR marker bands of this elusive phase of
      PVDF.

PMID- 25775385
TI  - Psychosocial functioning and glycemic control in emerging adults with Type 1
      diabetes: A 5-year follow-up study.
AB  - OBJECTIVE: The principal aim of this study was to examine the longitudinal
      interplay of depressive symptoms, diabetes-specific perceptions and distress, and
      glycemic control in emerging adults with Type 1 diabetes. METHODS: Emerging
      adults with Type 1 diabetes (18-30 years old) participated in a 2-wave
      longitudinal study spanning 5 years (N = 164 at Time 1). Patients completed
      questionnaires on depressive symptoms, diabetes-specific distress (treatment
      related, food-related, emotional, and social support problems), and illness
      perceptions (consequences and personal control) at baseline and follow-up. HbA1c
      values were obtained from treating clinicians. The authors investigated the
      directionality of effects using cross-lagged path analysis. RESULTS: Stronger
      perceptions of control predicted a relative decrease in treatment-related
      problems 5 years later, whereas stronger perceptions of consequences predicted a
      relative increase in depressive symptoms, treatment-related, food-related,
      emotional, and social support problems over time. Furthermore, higher depressive
      symptoms predicted a relative increase in social support problems 5 years later.
      None of the study variables were related to changes in glycemic control over
      time. CONCLUSIONS: Our findings stress the importance of addressing patients'
      perceptions and beliefs about their diabetes. Clinicians should find a delicate
      balance between stressing the importance of diabetes care and preventing patients
      from feeling overwhelmed or engulfed by the burden of diabetes care. Furthermore,
      our findings advocate for depression screening and treatment as key elements in
      holistic diabetes care, given the relatively high prevalence of elevated
      depressive symptoms in this population.

PMID- 25775386
TI  - Examining trait mindfulness, emotion dysregulation, and quality of life in
      multiple sclerosis.
AB  - OBJECTIVE: Dispositional mindfulness exhibits a positive association with quality
      of life (QoL). One potential mechanism for this association is enhanced emotion
      regulation abilities. Individuals with multiple sclerosis (MS) experience a range
      of physical, cognitive, and affective impairments, thus reducing overall QoL. The
      current cross-sectional study examines the relation between trait mindfulness and
      QoL, mediated by emotion dysregulation in individuals with MS. METHOD: Ninety
      five participants with self-reported MS completed an online survey that
      incorporated self-report measures of trait mindfulness, emotion dysregulation,
      and QoL. Although clinically significant depression was exclusionary, we observed
      a wide range of depressive symptoms in our sample. These scores were thus entered
      as a moderator in the mediation analysis. RESULTS: Dispositional mindfulness
      correlated positively with QoL, with lower emotion dysregulation partially
      mediating the correlation. Depression scores moderated the observed mediation,
      such that the effect was stronger in those with higher symptoms of depression.
      CONCLUSIONS: Trait mindfulness is positively associated with QoL in individuals
      with MS. Reduced emotion dysregulation may be a critical pathway linking
      mindfulness and QoL in MS, especially in those with higher symptoms of
      depression.

PMID- 25775388
TI  - Glyphosate loss by runoff and its relationship with phosphorus fertilization.
AB  - The aim of this study was to evaluate the relationship between glyphosate and
      phosphate fertilizer application and their contribution to surface water runoff
      contamination. The study was performed in Aquic Argiudoll soil (Tezanos Pinto
      series). Four treatments were assessed on three dates of rainfall simulation
      after fertilizer and herbicide application. The soluble phosphorus in runoff
      water was determined by a colorimetric method. For the determination of
      glyphosate and aminomethylphosphonic acid (AMPA), a method based on
      fluorenylmethyloxycarbonyl (FMOC) group derivatization, solid phase extraction
      (SPE) purification, and ultrahigh-performance liquid chromatography-tandem mass
      spectrometry (UHPLC-MS/MS) was employed. The application of phosphorus fertilizer
      resulted in an increased loss of glyphosate by runoff after 1 day of application.
      These results suggest the need for further study to understand the interactions
      and to determine appropriate application timing with the goal of reducing the
      pollution risk by runoff. 

PMID- 25775389
TI  - Corrigendum.
AB  - Clark, D. P. A., Dunn, A. K., Baguley, T. (2012). Testing the exclusivity effect
      in location memory.Memory. http://dx.doi.org/10.1080/09658211.2012.744421. When
      the above article was first published, a labelling correction was made to figure
      3 during peer review, the conditions accidentally became reordered and thus
      paired with the incorrect labels. The correct figure is below.

PMID- 25775390
TI  - Sulfated radix Cyathulae officinalis polysaccharides act as adjuvant via
      promoting the dendritic cell maturation and suppressing Treg frequency.
AB  - This study was conducted to evaluate the adjuvant potential of sulfated Radix
      Cyathulae officinalis Kuan polysaccharides (sRCPS) and their effects on specific
      cellular and humoral immune responses to hepatitis B subunit vaccine in mice. Our
      data demonstrated that sRCPS significantly promoted the rHBsAg-specific IgG,
      IgG1, IgG2a, and IgG2b antibody titers, the activities of natural killer cells
      (NK) and cytotoxic T lymphocytes (CTL), T cells proliferation, and phagocytic
      capacity of peritoneal macrophages. Furthermore, sRCPS increased the levels of IL
      4, IL-2, and IFN-gamma in CD4(+)T cells and the level of IFN-gamma in CD8(+)T
      cells. In addition, sRCPS enhanced the expression of CD40(+), CD80(+), CD86(+),
      MHC I and MHC II in dendritic cells (DCs) and upregulated the mRNA levels of MHC
      I, MHC II. sRCPS downregulated the frequency of CD4(+)CD25(+)Foxp3(+) Treg cells.
      sRCPS increased both cellular and humoral immune responses by upregulating DC
      maturation, and suppressing the frequency of Treg cells. 

PMID- 25775391
TI  - The role of satisfaction with social support on the psychological health of
      primiparous mothers in the perinatal period.
AB  - The aim of this study was to develop a satisfaction scale for social support and
      to investigate the relation of satisfaction with social support to the
      psychological health of primiparous mothers in terms of depressive symptoms,
      anxiety, and parental self-efficacy. We carried out a quantitative study during
      the last month of pregnancy (T1) and 6 weeks after birth (T2) including 235
      mothers who were expecting their first child in Geneva (Switzerland) from
      September 2010 to April 2012. The satisfaction scale for social support revealed
      five sources of support (from the spouse, young woman's mother, family, friends,
      professionals), each associated with different types of support (i.e., emotional,
      esteem, material, and informative). This scale showed good internal consistency
      for each factor. Moreover, the results revealed a relationship between
      satisfaction with social support and the mental health of mothers, in particular
      in the postnatal period for depressive symptoms, anxiety, and self-efficacy. This
      study highlights the important role of social support and the scale specifically
      developed during this period is a useful tool to investigate this aspect. 

PMID- 25775392
TI  - Evaluation of Paraoxonase-1 Activity in Chronic Obstructive Pulmonary Disease.

PMID- 25775393
TI  - Expression and significance of CDC25B, PED/PEA-15 in esophageal carcinoma.
AB  - OBJECTIVE: To explore the role of CDC25B, PED/PEA-15 in the development of
      esophageal carcinoma and its influence on the prognosis. METHODS: Fluorescence
      quantitative real-time PCR and immunohistochemistry methods were used to analyze
      the expression of CDC25B, PED/PEA-15 in esophageal carcinoma. Moreover, survival
      analysis was done using the Kaplan-Meier method. RESULTS: In 66 cases of
      esophageal cancer tissues, the relative content of CDC25B mRNA was 16.22 (13.93
      18.90). The positive expression rate of CDC25B protein was 48.5%, significantly
      higher than normal mucosa tissues (0%) (p<0.01). The relative content of PED/PEA
      15 mRNA was 12.47 (10.41-14.93). The positive expression rate of PED/PEA-15
      protein was 68.2%, significantly higher than normal mucosa tissues (17.6%)
      (p<0.01). The CDC25B protein expression was correlated with differentiation grade
      and depth of invasion (p<0.05). The PED/PEA-15 protein expression was related to
      differentiation grade, lymph node metastasis, and depth of invasion (p<0.05).
      Survival analysis showed that the mean survival time of PED/PEA-15-positive
      expression group was lower compared with the negative expression group
      (chi(2)=5.549, p=0.018). Analysis of the relationship between CDC25B and PED/PEA
      15 suggested that there was a positive correlation between them (r=4.061,
      p=0.044). CONCLUSION: Both CDC25B and PED/PEA-15 play a certain role in the
      carcinogenesis of esophageal cancer, and PED/PEA-15 has a greater influence on
      postoperative survival time. They will be the new diagnostic/therapeutic targets
      in esophageal carcinoma.

PMID- 25775394
TI  - Use of a functionalized introducer sheath and bioimpedance spectroscopy for real
      time detection of vascular access complications.
AB  - Internal bleeding complications (IBCs) occurring at vascular access sites are
      associated with worsening patient outcomes and increased costs. This study
      assessed the IBC detection capabilities of a bioimpedance spectroscopy (BS)
      monitoring system that uses a novel functionalized introducer sheath. The device
      was tested in three large animal models of a clinical IBC. A 120-mL perivascular
      saline injection after sheath insertion, a slow continuous perivascular saline
      injection of 2.6 mL min(-1) of saline and a vessel-puncture model were tested. In
      each case, a significant change in normalized impedance was detected compared to
      the controls. This study provides evidence that a functionalized vascular access
      sheath using BS can detect an intraprocedural vascular access IBC. Clinical use
      of the device could help guide patient care by directly detecting vascular access
      complications early, thereby preventing unnecessary diagnostic scans to rule out
      the presence of IBCs.

PMID- 25775395
TI  - Magnitude of the benefit of progression-free survival as a potential surrogate
      marker in phase 3 trials assessing targeted agents in molecularly selected
      patients with advanced non-small cell lung cancer: systematic review.
AB  - BACKGROUND: In evaluation of the clinical benefit of a new targeted agent in a
      phase 3 trial enrolling molecularly selected patients with advanced non-small
      cell lung cancer (NSCLC), overall survival (OS) as an endpoint seems to be of
      limited use because of a high level of treatment crossover for ethical reasons. A
      more efficient and useful indicator for assessing efficacy is needed. METHODS AND
      FINDINGS: We identified 18 phase 3 trials in the literature investigating EGFR
      tyrosine kinase inhibitor (TKIs) or ALK-TKIs, now approved for use to treat
      NSCLC, compared with standard cytotoxic chemotherapy (eight trials were performed
      in molecularly selected patients and ten using an "all-comer" design). Receiver
      operating characteristic analysis was used to identify the best threshold by
      which to divide the groups. Although trials enrolling molecularly selected
      patients and all-comer trials had similar OS-hazard ratios (OS-HRs) (0.99 vs.
      1.04), the former exhibited greater progression-free survival-hazard ratios (PFS
      HR) (mean, 0.40 vs. 1.01; P<0.01). A PFS-HR of 0.60 successfully distinguished
      between the two types of trials (sensitivity 100%, specificity 100%). The odds
      ratio for overall response was higher in trials with molecularly selected
      patients than in all-comer trials (mean: 6.10 vs. 1.64; P<0.01). An odds ratio of
      3.40 for response afforded a sensitivity of 88% and a specificity of 90%.
      CONCLUSION: The notably enhanced PFS benefit was quite specific to trials with
      molecularly selected patients. A PFS-HR cutoff of ~0.6 may help detect clinical
      benefit of molecular targeted agents in which OS is of limited use, although
      desired threshold might differ in an individual trial.

PMID- 25775396
TI  - Rational design of antibody protease inhibitors.
AB  - The bovine antibody BLV1H12, which has an ultralong CDR3H, provides a novel
      scaffold for engineering new functions into the antibody's variable region. By
      modifying the beta-strand "stalk" of BLV1H12 with sequences derived from natural
      or synthetic protease inhibitors, we have generated antibodies that inhibit
      bovine trypsin and human neutrophil elastase (HNE) with low nanomolar affinities.
      We were also able to generate a humanized variant using a human immunoglobulin
      scaffold that shares a high degree of homology with BLV1H12. Further optimization
      yielded a highly selective humanized anti-HNE antibody with sub-nanomolar
      affinity. This work demonstrates a novel strategy for generating antibodies with
      potent and selective inhibitory activities against extracellular proteases
      involved in human disease. 

PMID- 25775397
TI  - Soluble and meltable hyperbranched polyborosilazanes toward high-temperature
      stable SiBCN ceramics.
AB  - High-temperature stable siliconborocarbonitride (SiBCN) ceramics produced from
      single-source preceramic polymers have received increased attention in the last
      two decades. In this contribution, soluble and meltable polyborosilazanes with
      hyperbranched topology (hb-PBSZ) were synthesized via a convenient solvent-free,
      catalyst-free and one-pot A2 + B6 strategy, an aminolysis reaction of the A2
      monomer of dichloromethylsilane and the B6 monomer of
      tris(dichloromethylsilylethyl)borane in the presence of hexamethyldisilazane. The
      amine transition reaction between the intermediates of
      dichlorotetramethyldisilazane and tri(trimethylsilylmethylchlorosilylethyl)borane
      led to the formation of dendritic units of aminedialkylborons rather than
      trialkylborons. The cross-linked hb-PBSZ precursors exhibited a ceramic yield
      higher 80%. The resultant SiBCN ceramics with a boron atomic composition of 6.0
      8.5% and a representative formula of Si1B(0.19)C(1.21)N(0.39)O(0.08) showed high
      temperature stability and retained their amorphous structure up to 1600  degrees
      C. These hyperbranched polyborosilazanes with soluble and meltable
      characteristics provide a new perspective for the design of preceramic polymers
      possessing advantages for high-temperature stable polymer-derived ceramics with
      complex structures/shapes.

PMID- 25775398
TI  - Unique gene expression profile of the proliferating Xenopus tadpole tail blastema
      cells deciphered by RNA-sequencing analysis.
AB  - Organ regenerative ability depends on the animal species and the developmental
      stage. The molecular bases for variable organ regenerative ability, however,
      remain unknown. Previous studies have identified genes preferentially expressed
      in the blastema tissues in various animals, but transcriptome analysis of the
      isolated proliferating blastema cells has not yet been reported. In the present
      study, we used RNA-sequencing analysis to analyze the gene expression profile of
      isolated proliferating blastema cells of regenerating Xenopus laevis tadpole
      tails. We used flow cytometry to isolate proliferating cells, and non
      proliferating blastema cells, from regenerating tadpole tails as well as
      proliferating tail bud cells from tail bud embryos, the latter two of which were
      used as control cells, based on their DNA content. Among the 28 candidate genes
      identified by RNA-sequencing analysis, quantitative reverse transcription
      polymerase chain reaction identified 10 genes whose expression was enriched in
      regenerating tadpole tails compared with non-regenerating tadpole tails or tails
      from the tail bud embryos. Among them, whole mount in situ hybridization revealed
      that chromosome segregation 1-like and interleukin 11 were expressed in the broad
      area of the tail blastema, while brevican, lysyl oxidase, and keratin 18 were
      mainly expressed in the notochord bud in regenerating tails. We further combined
      whole mount in situ hybridization with immunohistochemistry for the incorporated
      5-bromo-2-deoxyuridine to confirm that keratin 18 and interleukin 11 were
      expressed in the proliferating tail blastema cells. Based on the proposed
      functions of their homologs in other animal species, these genes might have roles
      in the extracellular matrix formation in the notochord bud (brevican and lysyl
      oxidase), cell proliferation (chromosome segregation 1-like and keratin 18), and
      in the maintenance of the differentiation ability of proliferating blastema cells
      (interleukin 11) in regenerating tadpole tails. 

PMID- 25775399
TI  - Fibroblast activation protein overexpression and clinical implications in solid
      tumors: a meta-analysis.
AB  - OBJECTIVE: Fibroblast activation protein (FAP) plays a vital role in tumor
      invasion and metastasis. Previous studies have reported its prognostic value in
      different tumors. However, the results of these reports remain controversial. In
      this study, a meta-analysis was performed to clarify this issue. METHODS: A
      search of the PubMed, Embase and CNKI databases was conducted to analyze relevant
      articles. The outcomes included the relations between FAP expression and
      histological differentiation, tumor invasion, lymph node metastasis, distant
      metastasis and overall survival (OS). Sensitivity analysis by FAP expression in
      different cells and tumor types were further subjected to sensitivity analyses as
      subgroups. Pooled odds ratios (ORs) and hazard ratios (HRs) were evaluated using
      the random-effects model. RESULTS: The global analysis included 15 studies
      concerning various solid tumors. For global analysis, FAP overexpression in tumor
      tissue displayed significant associations with poor OS and tumor progression (OS:
      HR = 2.18, P = 0.004; tumor invasion: OR = 4.48, P = 0.007; and lymph node
      metastasis: OR = 3.80, P = 0.004). The subgroup analyses yielded two notable
      results. First, the relation between FAP overexpression and poor OS and tumor
      lymph node metastasis was closer in the patients with FAP expression in tumor
      cells. Second, the pooled analyses of colorectal cancers or pancreatic cancers
      all indicated that FAP overexpression was associated with a detrimental OS (HR:
      1.72, P = 0.009; HR: 3.18, P = 0.005, respectively). The magnitude of this effect
      was not statistically significant compared with that in patients with non
      colorectal cancers or non-pancreatic cancers. These analyses did not display a
      statistically significant correlation between FAP expression and histological
      differentiation and distant metastasis in all of the groups. CONCLUSIONS: FAP
      expression is associated with worse prognosis in solid tumors, and this
      association is particularly pronounced if FAP overexpression is found in the
      tumor cells rather than the stroma.

PMID- 25775401
TI  - Correction: a novel reproductive mode in frogs: a new species of fanged frog with
      internal fertilization and birth of tadpoles.

PMID- 25775400
TI  - Involvement of serotonin transporter gene polymorphisms (5-HTT) in impulsive
      behavior in the japanese population.
AB  - The serotonergic pathway has been implicated in the pathogenesis of impulsivity,
      and sensitivity to aversive outcomes may be linked to serotonin (5-HT) levels.
      Polymorphisms in the gene that encodes the serotonin transporter (5-HTT), which
      have differential effects on the level of serotonin transmission, display
      alternate responses to aversive stimuli. However, recent studies have shown that
      5-HT does not affect motor function, which suggests that the functioning of the
      serotonin-transporter-linked polymorphic region (5-HTTLPR) does not directly
      affect the behavioral regulatory process itself, but instead exerts an effect via
      the evaluation of the potential risk associated with particular behavioral
      outputs. The aim of the present study was to examine the effect of specific 5
      HTTLPR genotypes on the motor regulatory process, as observed during a Go/Nogo
      punishment feedback task. 5-HTT gene-linked promoter polymorphisms were analyzed
      by polymerase chain reaction, using lymphocytes from 61 healthy Japanese
      volunteers. Impulsivity was defined as the number of commission errors
      (responding when one should not) made during a Go/Nogo task. We found that the
      s/s genotype group made fewer impulsive responses, specifically under aversive
      conditions for committing such errors, compared to those in the s/l group,
      without affecting overall motor inhibition. These results suggest that 5-HTTLPRs
      do not directly affect the behavioral regulatory process itself, but may instead
      exert an effect on the evaluation of potential risk. The results also indicate
      that under such aversive conditions, decreased expression of 5-HTT may promote
      motor inhibitory control. 

PMID- 25775402
TI  - Platelet recruitment promotes keratocyte repopulation following corneal
      epithelial abrasion in the mouse.
AB  - Corneal abrasion not only damages the epithelium but also induces stromal
      keratocyte death at the site of injury. While a coordinated cascade of
      inflammatory cell recruitment facilitates epithelial restoration, it is unclear
      if this cascade is necessary for keratocyte recovery. Since platelet and
      neutrophil (PMN) recruitment after corneal abrasion is beneficial to epithelial
      wound healing, we wanted to determine if these cells play a role in regulating
      keratocyte repopulation after epithelial abrasion. A 2 mm diameter central
      epithelial region was removed from the corneas of C57BL/6 wildtype (WT), P
      selectin deficient (P-sel-/-), and CD18 hypomorphic (CD18hypo) mice using the
      Algerbrush II. Corneas were studied at 6h intervals out to 48h post-injury to
      evaluate platelet and PMN cell numbers; additional corneas were studied at 1, 4,
      14, and 28 days post injury to evaluate keratocyte numbers. In WT mice,
      epithelial abrasion induced a loss of anterior central keratocytes and keratocyte
      recovery was rapid and incomplete, reaching ~70% of uninjured baseline values by
      4 days post-injury but no further improvement at 28 days post-injury. Consistent
      with a beneficial role for platelets and PMNs in wound healing, keratocyte
      recovery was significantly depressed at 4 days post-injury (~30% of uninjured
      baseline) in P-sel-/- mice, which are known to have impaired platelet and PMN
      recruitment after corneal abrasion. Passive transfer of platelets from WT, but
      not P-sel-/-, into P-sel-/- mice prior to injury restored anterior central
      keratocyte numbers at 4 days post-injury to P-sel-/- uninjured baseline levels.
      While PMN infiltration in injured CD18hypo mice was similar to injured WT mice,
      platelet recruitment was markedly decreased and anterior central keratocyte
      recovery was significantly reduced (~50% of baseline) at 4-28 days post-injury.
      Collectively, the data suggest platelets and platelet P-selectin are critical for
      efficient keratocyte recovery after corneal epithelial abrasion. 

PMID- 25775403
TI  - SEPT12/SPAG4/LAMINB1 complexes are required for maintaining the integrity of the
      nuclear envelope in postmeiotic male germ cells.
AB  - Male infertility affects approximately 50% of all infertile couples. The male
      related causes of intracytoplasmic sperm injection failure include the absence of
      sperm, immotile or immature sperm, and sperm with structural defects such as
      those caused by premature chromosomal condensation and DNA damage. Our previous
      studies based on a knockout mice model indicated that SEPT12 proteins are
      critical for the terminal morphological formation of sperm. SEPT12 mutations in
      men result in teratozospermia and oligozospermia. In addition, the spermatozoa
      exhibit morphological defects of the head and tail, premature chromosomal
      condensation, and nuclear damage. However, the molecular functions of SEPT12
      during spermatogenesis remain unclear. To determine the molecular functions of
      SEPT12, we applied a yeast 2-hybrid system to identify SEPT12 interactors. Seven
      proteins that interact with SEPT12 were identified: SEPT family proteins (SEPT4
      and SEPT6), nuclear or nuclear membrane proteins (protamine 2, sperm-associated
      antigen 4, and NDC1 transmembrane nucleoproine), and sperm-related structural
      proteins (pericentriolar material 1 and obscurin-like 1). Sperm-associated
      antigen 4 (SPAG4; also known as SUN4) belongs to the SUN family of proteins and
      acts as a linker protein between nucleoskeleton and cytoskeleton proteins and
      localizes in the nuclear membrane. We determined that SEPT12 interacts with SPAG4
      in a male germ cell line through coimmunoprecipitation. During human
      spermiogenesis, SEPT12 is colocalized with SPAG4 near the nuclear periphery in
      round spermatids and in the centrosome region in elongating spermatids.
      Furthermore, we observed that SEPT12/SPAG4/LAMINB1 formed complexes and were
      coexpressed in the nuclear periphery of round spermatids. In addition, mutated
      SEPT12, which was screened from an infertile man, affected the integration of
      these nuclear envelope complexes through coimmunoprecipitation. This was the
      first study that suggested that SEPT proteins link to the SUN/LAMIN complexes
      during the formation of nuclear envelopes and are involved in the development of
      postmeiotic germ cells. 

PMID- 25775404
TI  - Proteasome inhibition augments new protein accumulation early in long-term
      synaptic plasticity and rescues adverse Abeta effects on protein synthesis.
AB  - Protein degradation plays a critical role in synaptic plasticity, but the
      molecular mechanisms are not well understood. Previously we showed that
      proteasome inhibition enhances the early induction part of long-term synaptic
      plasticity for which protein synthesis is essential. In this study, we tested the
      effect of proteasome inhibition on protein synthesis using a chemically induced
      long-lasting synaptic plasticity (cLTP) in the murine hippocampus as a model
      system. Our metabolic labeling experiments showed that cLTP induction increases
      protein synthesis and proteasome inhibition enhances the amount of newly
      synthesized proteins. We then found that amyloid beta (Abeta), a peptide
      contributing to Alzheimer's pathology and impairment of synaptic plasticity,
      blocks protein synthesis increased by cLTP. This blockade can be reversed by
      prior proteasome inhibition. Thus, our work reveals interactions between protein
      synthesis and protein degradation and suggests a possible way to exploit protein
      degradation to rescue adverse Abeta effects on long-term synaptic plasticity.

PMID- 25775405
TI  - Derricin and derricidin inhibit Wnt/beta-catenin signaling and suppress colon
      cancer cell growth in vitro.
AB  - Overactivation of the Wnt/beta-catenin pathway in adult tissues has been
      implicated in many diseases, such as colorectal cancer. Finding chemical
      substances that can prevent this phenomenon is an emerging problem. Recently,
      several natural compounds have been described as Wnt/beta-catenin inhibitors and
      might be promising agents for the control of carcinogenesis. Here, we describe
      two natural substances, derricin and derricidin, belonging to the chalcone
      subclass, that show potent transcriptional inhibition of the Wnt/beta-catenin
      pathway. Both chalcones are able to affect the cell distribution of beta-catenin,
      and inhibit Wnt-specific reporter activity in HCT116 cells and in Xenopus
      embryos. Derricin and derricidin also strongly inhibited canonical Wnt activity
      in vitro, and rescued the Wnt-induced double axis phenotype in Xenopus embryos.
      As a consequence of Wnt/beta-catenin inhibition, derricin and derricidin
      treatments reduce cell viability and lead to cell cycle arrest in colorectal
      cancer cell lines. Taken together, our results strongly support these chalcones
      as novel negative modulators of the Wnt/beta-catenin pathway and colon cancer
      cell growth in vitro. 

PMID- 25775406
TI  - Insights into European drug shortages: a survey of hospital pharmacists.
AB  - Drug shortages are a complex and global phenomenon. When a drug cannot be
      delivered at the moment of patient demand, every stakeholder in the health care
      system is affected. The aim of this study was to investigate the characteristics,
      clinical impact, financial impact and management of drug shortages in European
      hospital pharmacies and identify opportunities for prevention and mitigation of
      drug shortages in Europe. An online survey was designed based on a review of the
      literature and interviews and was sent to subscribers of Hospital Pharmacy Europe
      between June and September 2013. Forty-five percent of respondents (n = 161)
      indicated that life sustaining or life preserving drugs such as oncology drugs
      were affected by drug shortages. More than 30% of respondents indicated that drug
      shortages in Europe were always or often associated with increased costs for
      hospitals, increased personnel costs and more expensive alternative drugs (n =
      161). On the question when information about a drug shortage was obtained, 42% of
      respondents answered that information from the pharmaceutical company was
      obtained at the time of no delivery, 50% indicated that information from the
      wholesaler was obtained at the time of no delivery, while 40% of respondents
      indicated that information was never or rarely received from the government (n =
      161). Fifty seven percent of respondents strongly agreed that an obligation to
      the producer to notify further shortages could help to solve the problem (n =
      161). These results showed that pharmaceutical companies and wholesalers are
      already involved in the management of drug shortages, while a role is still
      reserved for the government. Mandatory notification in advance and centralized
      information can help to reduce workload for hospital pharmacists, will allow
      early anticipation of drug shortages and will facilitate mitigation of the
      clinical impact on patients. 

PMID- 25775407
TI  - Synergetic Protein Factors That Improve rhGM-CSF Absorption via an Oral Route
      Exist in Silkworm Pupae.
AB  - Recent studies have demonstrated that recombinant human granulocyte macrophage
      colony-stimulating factor (rhGM-CSF) produced by the silkworm pupae bioreactor is
      absorbed into blood through oral administration and functions as an active
      cytokine. The aim of this study was to further examine and identify synergetic
      protein factors in silkworm pupae that improve rhGM-CSF absorption via an oral
      route. The concentrations of rhGM-CSF in serum were evaluated in mice after oral
      administration of rhGM-CSF using different chemical compositions of silkworm
      pupae as pharmaceutical excipients. The experimental data revealed that the
      supernatant lyophilized powder (SLP) of a homogenized slurry of silkworm pupae
      caused a significant increase in the rhGM-CSF level in blood when rhGM-CSF was
      orally administered with SLP, suggesting that synergetic protein factors that
      improve the oral absorption of rhGM-CSF primarily exist in SLP. As shown by
      scanning electron microscopy, microspheres were formed when rhGM-CSF was coated
      with SLP. Animal experimental data showed that the absorption of orally
      administered rhGM-CSF through the gastrointestinal (GI) tract primarily resulted
      from protein factors present in the SLP retentate obtained after 10 kDa
      ultrafiltration. Surface plasmon resonance spectroscopy analysis demonstrated
      that several protein factors present in the SLP retentate obtained after 10 kDa
      ultrafiltration were bound to rhGM-CSF. Proteins bound to rhGM-CSF by liquid
      chromatography-mass spectrometry were identified as chymotrypsin inhibitor SCI-II
      precursor, cationic peptide CP8 precursor, Kazal-type proteinase inhibitor, and
      chymotrypsin inhibitor SCI-I. These findings indicate that these proteinase
      inhibitors play an important role in improving rhGM-CSF absorption in the GI
      tract. 

PMID- 25775408
TI  - Rate constant and thermochemistry for K + O2 + N2 = KO2 + N2.
AB  - The addition reaction of potassium atoms with oxygen has been studied using the
      collinear photofragmentation and atomic absorption spectroscopy (CPFAAS) method.
      KCl vapor was photolyzed with 266 nm pulses and the absorbance by K atoms at
      766.5 nm was measured at various delay times with a narrow line width diode
      laser. Experiments were carried out with O2/N2 mixtures at a total pressure of 1
      bar, over 748-1323 K. At the lower temperatures single exponential decays of [K]
      yielded the third-order rate constant for addition, kR1, whereas at higher
      temperatures equilibration was observed in the form of double exponential decays
      of [K], which yielded both kR1 and the equilibrium constant for KO2 formation.
      kR1 can be summarized as 1.07 * 10(-30)(T/1000 K)(-0.733) cm(6) molecule(-2) s(
      1). Combination with literature values leads to a recommended kR1 of 5.5 * 10(
      26)T(-1.55) exp(-10/T) cm(6) molecule(-2) s(-1) over 250-1320 K, with an error
      limit of a factor of 1.5. A van't Hoff analysis constrained to fit the computed
      DeltaS298 yields a K-O2 bond dissociation enthalpy of 184.2 +/- 4.0 kJ mol(-1) at
      298 K and DeltafH298(KO2) = -95.2 +/- 4.1 kJ mol(-1). The corresponding D0 is
      181.5 +/- 4.0 kJ mol(-1). This value compares well with a CCSD(T) extrapolation
      to the complete basis set limit, with all electrons correlated, of 177.9 kJ mol(
      1). 

PMID- 25775409
TI  - Second trimester angiotensing-converting enzyme and uterine artery Doppler as
      predictors of preeclampsia in a high-risk population.
AB  - OBJECTIVE: To investigate whether serum angiotensing-converting enzyme (ACE) and
      uterine artery Doppler (UAD) are useful markers as predictors of preeclampsia
      (PE) in a high-risk population. METHODS: Patients at risk of PE (n = 68) were
      subclassified as having PE (n = 8) or no PE (n = 60). Blood samples were obtained
      between 19 and 22 weeks of gestation. Doppler ultrasound of the uterine arteries
      was done at the time of blood sampling. Maternal serum ACE was determined through
      spectrophotometry assay (A15 Biosystem, ATOM, Barcelona, Spain). RESULTS:
      Comparing the group who presented PE with the one who was not developed it, we
      found significant differences for ACE (54.2 +/- 21.2, 38.1 +/- 12.3 U/L; p =
      0.003); the pulsatility index (PI) (1.2 +/- 0, 3.1 +/- 0.3; p = 0.032) and
      resistance index (RI) (0.7 +/- 0.1, 0.5 +/- 0.1; p = 0.004). The AUC for ACE was
      0.724, so we selected the cutoff of 36.5 U/L (sensitivity: 62.5% and specificity:
      86.7%). The AUC for PI was 0.652 choosing a cutoff of 1.4 (sensitivity: 57.1% and
      specificity: 93.1%). The AUC for RI was 0.712 and the cutoff of 0.7 (sensitivity
      of 71.4% and specificity: 89.6%). The combination that allowed us to increase the
      diagnostic performance was the ACE+RI with Doppler study, increasing the AUC to
      0.872. CONCLUSIONS: ACE, PI and RI as parameters of Doppler study were useful
      predictors of PE in the second trimester of gestation. The best combination to
      increase the diagnostic performance was ACE with the RI.

PMID- 25775410
TI  - Mating frequencies of honey bee queens (Apis mellifera L.) in a population of
      feral colonies in the Northeastern United States.
AB  - Across their introduced range in North America, populations of feral honey bee
      (Apis mellifera L.) colonies have supposedly declined in recent decades as a
      result of exotic parasites, most notably the ectoparasitic mite Varroa
      destructor. Nonetheless, recent studies have documented several wild populations
      of colonies that have persisted. The extreme polyandry of honey bee queens-and
      the increased intracolony genetic diversity it confers-has been attributed, in
      part, to improved disease resistance and may be a factor in the survival of these
      populations of feral colonies. We estimated the mating frequencies of queens in
      feral colonies in the Arnot Forest in New York State to determine if the level of
      polyandry of these queens is especially high and so might contribute to their
      survival success. We genotyped the worker offspring from 10 feral colonies in the
      Arnot Forest of upstate New York, as well as those from 20 managed colonies
      closest to this forest. We found no significant differences in mean mating
      frequency between the feral and managed queens, suggesting that queens in the
      remote, low-density population of colonies in the Arnot Forest are neither mate
      limited nor adapted to mate at an especially high frequency. These findings
      support the hypothesis that the hyperpolyandry of honey bees has been shaped on
      an evolutionary timescale rather than on an ecological one. 

PMID- 25775411
TI  - Location-allocation and accessibility models for improving the spatial planning
      of public health services.
AB  - This study integrated accessibility and location-allocation models in geographic
      information systems as a proposed strategy to improve the spatial planning of
      public health services. To estimate the spatial accessibility, we modified the
      two-step floating catchment area (2SFCA) model with a different impedance
      function, a Gaussian weight for competition among service sites, a friction
      coefficient, distances along a street network based on the Dijkstra's algorithm
      and by performing a vectorial analysis. To check the accuracy of the strategy, we
      used the data from the public sterilization program for the dogs and cats of
      Bogot'a, Colombia. Since the proposed strategy is independent of the service, it
      could also be applied to any other public intervention when the capacity of the
      service is known. The results of the accessibility model were consistent with the
      sterilization program data, revealing that the western, central and northern
      zones are the most isolated areas under the sterilization program. Spatial
      accessibility improvement was sought by relocating the sterilization sites using
      the maximum coverage with finite demand and the p-median models. The relocation
      proposed by the maximum coverage model more effectively maximized the spatial
      accessibility to the sterilization service given the non-uniform distribution of
      the populations of dogs and cats throughout the city. The implementation of the
      proposed strategy would provide direct benefits by improving the effectiveness of
      different public health interventions and the use of financial and human
      resources. 

PMID- 25775412
TI  - Commentary on Historical Trauma, Substance Use, and Indigenous People: Seven
      Generations From a "Big Event".

PMID- 25775413
TI  - Topological crystalline metal in orthorhombic perovskite iridates.
AB  - Since topological insulators were theoretically predicted and experimentally
      observed in semiconductors with strong spin-orbit coupling, increasing attention
      has been drawn to topological materials that host exotic surface states. These
      surface excitations are stable against perturbations since they are protected by
      global or spatial/lattice symmetries. Following the success in achieving various
      topological insulators, a tempting challenge now is to search for metallic
      materials with novel topological properties. Here we predict that orthorhombic
      perovskite iridates realize a new class of metals dubbed topological crystalline
      metals, which support zero-energy surface states protected by certain lattice
      symmetry. These surface states can be probed by photoemission and tunnelling
      experiments. Furthermore, we show that by applying magnetic fields, the
      topological crystalline metal can be driven into other topological metallic
      phases, with different topological properties and surface states. 

PMID- 25775414
TI  - Comparison of methods for renal risk prediction in patients with type 2 diabetes
      (ZODIAC-36).
AB  - BACKGROUND: Patients with diabetes are at high risk of death prior to reaching
      end-stage renal disease, but most models predicting the risk of kidney disease do
      not take this competing risk into account. We aimed to compare the performance of
      Cox regression and competing risk models for prediction of early- and late-stage
      renal complications in type 2 diabetes. METHODS: Patients with type 2 diabetes
      participating in the observational ZODIAC study were included. Prediction models
      for (micro)albuminuria and 50% increase in serum creatinine (SCr) were developed
      using Cox regression and competing risk analyses. Model performance was assessed
      by discrimination and calibration. RESULTS: During a total follow-up period of 10
      years, 183 out of 640 patients (28.6%) with normoalbuminuria developed
      (micro)albuminuria, and 22 patients (3.4%) died without developing
      (micro)albuminuria (i.e. experienced the competing event). Seventy-nine out of
      1,143 patients (6.9%) reached the renal end point of 50% increase in SCr, while
      219 (19.2%) died without developing the renal end point. Performance of the Cox
      and competing risk models predicting (micro)albuminuria was similar and
      differences in predicted risks were small. However, the Cox model increasingly
      overestimated the risk of increase in SCr in presence of a substantial number of
      competing events, while the performance of the competing risk model was quite
      good. CONCLUSIONS: In this study, we demonstrated that, in case of substantial
      numbers of competing events, it is important to account for the competing risk of
      death in renal risk prediction in patients with type 2 diabetes.

PMID- 25775415
TI  - A crystal structure of the Dengue virus NS5 protein reveals a novel inter-domain
      interface essential for protein flexibility and virus replication.
AB  - Flavivirus RNA replication occurs within a replication complex (RC) that
      assembles on ER membranes and comprises both non-structural (NS) viral proteins
      and host cofactors. As the largest protein component within the flavivirus RC,
      NS5 plays key enzymatic roles through its N-terminal methyltransferase (MTase)
      and C-terminal RNA-dependent-RNA polymerase (RdRp) domains, and constitutes a
      major target for antivirals. We determined a crystal structure of the full-length
      NS5 protein from Dengue virus serotype 3 (DENV3) at a resolution of 2.3 A in the
      presence of bound SAH and GTP. Although the overall molecular shape of NS5 from
      DENV3 resembles that of NS5 from Japanese Encephalitis Virus (JEV), the relative
      orientation between the MTase and RdRp domains differs between the two
      structures, providing direct evidence for the existence of a set of discrete
      stable molecular conformations that may be required for its function. While the
      inter-domain region is mostly disordered in NS5 from JEV, the NS5 structure from
      DENV3 reveals a well-ordered linker region comprising a short 310 helix that may
      act as a swivel. Solution Hydrogen/Deuterium Exchange Mass Spectrometry (HDX-MS)
      analysis reveals an increased mobility of the thumb subdomain of RdRp in the
      context of the full length NS5 protein which correlates well with the analysis of
      the crystallographic temperature factors. Site-directed mutagenesis targeting the
      mostly polar interface between the MTase and RdRp domains identified several
      evolutionarily conserved residues that are important for viral replication,
      suggesting that inter-domain cross-talk in NS5 regulates virus replication.
      Collectively, a picture for the molecular origin of NS5 flexibility is emerging
      with profound implications for flavivirus replication and for the development of
      therapeutics targeting NS5. 

PMID- 25775416
TI  - DACH1 inhibits SNAI1-mediated epithelial-mesenchymal transition and represses
      breast carcinoma metastasis.
AB  - Epithelial-mesenchymal transition (EMT) has a major role in cancer progression
      and metastasis. However, the specific mechanism of transcriptional repression
      involved in this process remains largely unknown. Dachshund homologue 1 (DACH1)
      expression is lost in invasive breast cancer with poor prognosis, and the role of
      DACH1 in regulating breast cancer metastasis is poorly understood. In this study,
      significant correlation between the expression of DACH1 and the morphology of
      breast cancer cells was observed. Subsequent investigation into the relationship
      between DACH1 and EMT showed that overexpression of DACH1 in ZR-75-30 cells
      induced a shift towards epithelial morphology and cell-cell adhesion, as well as
      increased the expression of the epithelial marker E-cadherin and suppressed cell
      migration and invasion. In contrast, silencing DACH1 in MCF-7 and T47D cells
      disrupted the epithelial morphology and cell-cell contact, reduced the expression
      of E-cadherin, and induced cell migration and invasion. DACH1 also specifically
      interacted with SNAI1, but not SNAI2, to form a complex, which could bind to the
      E-box on the E-cadherin promoter in an SNAI1-dependent manner. DACH1 inhibited
      the transcriptional activity of SNAI1, leading to the activation of E-cadherin in
      breast cancer cells. Furthermore, the level of DACH1 also correlated with the
      extent of metastasis in a mouse model. DACH1 overexpression significantly
      decreased the metastasis and growth of 4T1/Luc cells in BALB/c mice. Analysis of
      tissue samples taken from human breast cancers showed a significant correlation
      between the expression of DACH1 and E-cadherin in SNAI1-positive breast cancer.
      Collectively, our data identified a new mechanistic pathway for the regulation of
      EMT and metastasis of breast cancer cells, one that is based on the regulation of
      E-cadherin expression by direct DACH1-SNAI1 interaction. 

PMID- 25775417
TI  - Perioperative cardiovascular care for patients undergoing noncardiac surgical
      intervention.
AB  - The field of perioperative medicine has garnered legitimacy during the past 3
      decades. Adverse cardiovascular events in the perioperative period account for
      significant morbidity and mortality. Although testing patients preoperatively to
      detect ischemia and identify those who may benefit from modifications in care is
      a tempting strategy, risk assessment should account for posterior probability.
      Validated risk stratification tools, such as the Revised Cardiac Risk Index or
      the National Surgical Quality Improvement Program risk calculator, can assist in
      the identification of patients for whom preoperative noninvasive testing is
      justified and may change the plan of care. Furthermore, current guidelines
      emphasize that prophylactic coronary revascularization should not be performed
      exclusively for the purposes of reducing the risk of perioperative events. There
      has been enthusiasm for medical therapies that may reduce the risk of adverse
      cardiovascular events in the perioperative period. Current guidelines encourage
      the perioperative use of beta-blockade in patients already receiving such therapy
      and caution against initiating such therapy on the day of the surgical procedure.
      Reduction of morbidity and mortality in the perioperative period relies on an
      understanding of the myriad physiological perturbations in this period and
      thoughtful selection of patients for further testing and treatment. 

PMID- 25775418
TI  - Inotuzumab ozogamicin in B-cell acute lymphoblastic leukemias and non-Hodgkin's
      lymphomas.
AB  - INTRODUCTION: The expression profile of the CD22 antigen and its role in B-cell
      function make it an important target in B-cell leukemias and lymphomas.
      Inotuzumab ozogamicin (IO), a humanized monoclonal antibody targeting CD22, is
      one of the most promising monoclonal antibodies for the treatment of
      relapsed/refractory B-cell acute lymphoblastic leukemia (ALL). AREAS COVERED:
      This article reviews the current literature of IO in adult leukemias and
      lymphomas. EXPERT OPINION: Single-agent IO has demonstrated activity in patients
      with relapsed B-cell ALL and non-Hodgkin lymphoma (NHL). It has also demonstrated
      favorable early results when combined with chemotherapy in older patients with
      ALL. There is potential for IO to be combined with other targeted therapies under
      development for these diseases; data are still early and further studies of IO
      are warranted. While the pivotal randomized study of IO for relapsed NHL versus
      physician's choice did not show a statistically significant advantage in response
      rate, the results of the pivotal study in ALL are not yet available.

PMID- 25775421
TI  - Potential threats posed by new or emerging marine biotoxins in UK waters and
      examination of detection methodology used in their control: brevetoxins.
AB  - Regular occurrence of brevetoxin-producing toxic phytoplankton in commercial
      shellfishery areas poses a significant risk to shellfish consumer health.
      Brevetoxins and their causative toxic phytoplankton are more limited in their
      global distribution than most marine toxins impacting commercial shellfisheries.
      On the other hand, trends in climate change could conceivably lead to increased
      risk posed by these toxins in UK waters. A request was made by UK food safety
      authorities to examine these toxins more closely to aid possible management
      strategies, should they pose a threat in the future. At the time of writing,
      brevetoxins have been detected in the Gulf of Mexico, the Southeast US coast and
      in New Zealand waters, where regulatory levels for brevetoxins in shellfish have
      existed for some time. This paper reviews evidence concerning the prevalence of
      brevetoxins and brevetoxin-producing phytoplankton in the UK, together with
      testing methodologies. Chemical, biological and biomolecular methods are
      reviewed, including recommendations for further work to enable effective testing.
      Although the focus here is on the UK, from a strategic standpoint many of the
      topics discussed will also be of interest in other parts of the world since new
      and emerging marine biotoxins are of global concern. 

PMID- 25775422
TI  - 6-bromohypaphorine from marine nudibranch mollusk Hermissenda crassicornis is an
      agonist of human alpha7 nicotinic acetylcholine receptor.
AB  - 6-Bromohypaphorine (6-BHP) has been isolated from the marine sponges Pachymatisma
      johnstoni, Aplysina sp., and the tunicate Aplidium conicum, but data on its
      biological activity were not available. For the nudibranch mollusk Hermissenda
      crassicornis no endogenous compounds were known, and here we describe the
      isolation of 6-BHP from this mollusk and its effects on different nicotinic
      acetylcholine receptors (nAChR). Two-electrode voltage-clamp experiments on the
      chimeric alpha7 nAChR (built of chicken alpha7 ligand-binding and glycine
      receptor transmembrane domains) or on rat alpha4beta2 nAChR expressed in Xenopus
      oocytes revealed no action of 6-BHP. However, in radioligand analysis, 6-BHP
      competed with radioiodinated alpha-bungarotoxin for binding to human alpha7 nAChR
      expressed in GH4C1 cells (IC50 23 +/- 1 MUM), but showed no competition on muscle
      type nAChR from Torpedo californica. In Ca2+-imaging experiments on the human
      alpha7 nAChR expressed in the Neuro2a cells, 6-BHP in the presence of PNU120596
      behaved as an agonist (EC50 ~80 MUM). To the best of our knowledge, 6-BHP is the
      first low-molecular weight compound from marine source which is an agonist of the
      nAChR subtype. This may have physiological importance because H. crassicornis,
      with its simple and tractable nervous system, is a convenient model system for
      studying the learning and memory processes. 

PMID- 25775423
TI  - Acetylated chitosan oligosaccharides act as antagonists against glutamate-induced
      PC12 cell death via Bcl-2/Bax signal pathway.
AB  - Chitosan oligosaccharides (COSs), depolymerized products of chitosan composed of
      beta-(1->4) D-glucosamine units, have broad range of biological activities such
      as antitumour, antifungal, and antioxidant activities. In this study,
      peracetylated chitosan oligosaccharides (PACOs) and N-acetylated chitosan
      oligosaccharides (NACOs) were prepared from the COSs by chemcal modification. The
      structures of these monomers were identified using NMR and ESI-MS spectra. Their
      antagonist effects against glutamate-induced PC12 cell death were investigated.
      The results showed that pretreatment of PC12 cells with the PACOs markedly
      inhibited glutamate-induced cell death in a concentration-dependent manner. The
      PACOs were better glutamate antagonists compared to the COSs and the NACOs,
      suggesting the peracetylation is essential for the neuroprotective effects of
      chitosan oligosaccharides. In addition, the PACOs pretreatment significantly
      reduced lactate dehydrogenase release and reactive oxygen species production. It
      also attenuated the loss of mitochondrial membrane potential. Further studies
      indicated that the PACOs inhibited glutamate-induced cell death by preventing
      apoptosis through depressing the elevation of Bax/Bcl-2 ratio and caspase-3
      activation. These results suggest that PACOs might be promising antagonists
      against glutamate-induced neural cell death.

PMID- 25775424
TI  - Lumazine peptides from the marine-derived fungus Aspergillus terreus.
AB  - Terrelumamides A (1) and B (2), two new lumazine-containing peptides, were
      isolated from the culture broth of the marine-derived fungus Aspergillus terreus.
      From the results of combined spectroscopic and chemical analyses, the structures
      of these compounds were determined to be linear assemblies of 1-methyllumazine-6
      carboxylic acid, an amino acid residue and anthranilic acid methyl ester
      connected by peptide bonds. These new compounds exhibited pharmacological
      activity by improving insulin sensitivity, which was evaluated in an adipogenesis
      model using human bone marrow mesenchymal stem cells. In addition, the compounds
      exhibited fluorescence changes upon binding to DNA, demonstrating their potential
      applications to DNA sequence recognition. 

PMID- 25775425
TI  - Biotransformation of the mycotoxin deoxynivalenol in fusarium resistant and
      susceptible near isogenic wheat lines.
AB  - In this study, a total of nine different biotransformation products of the
      Fusarium mycotoxin deoxynivalenol (DON) formed in wheat during detoxification of
      the toxin are characterized by liquid chromatography-high resolution mass
      spectrometry (LC-HRMS). The detected metabolites suggest that DON is conjugated
      to endogenous metabolites via two major metabolism routes, namely 1)
      glucosylation (DON-3-glucoside, DON-di-hexoside, 15-acetyl-DON-3-glucoside, DON
      malonylglucoside) and 2) glutathione conjugation (DON-S-glutathione, "DON-2H"-S
      glutathione, DON-S-cysteinyl-glycine and DON-S-cysteine). Furthermore,
      conjugation of DON to a putative sugar alcohol (hexitol) was found. A molar mass
      balance for the cultivar 'Remus' treated with 1 mg DON revealed that under the
      test conditions approximately 15% of the added DON were transformed into DON-3
      glucoside and another 19% were transformed to the remaining eight
      biotransformation products or irreversibly bound to the plant matrix.
      Additionally, metabolite abundance was monitored as a function of time for each
      DON derivative and was established for six DON treated wheat lines (1 mg/ear)
      differing in resistance quantitative trait loci (QTL) Fhb1 and/or Qfhs.ifa-5A.
      All cultivars carrying QTL Fhb1 showed similar metabolism kinetics: Formation of
      DON-Glc was faster, while DON-GSH production was less efficient compared to
      cultivars which lacked the resistance QTL Fhb1. Moreover, all wheat lines
      harboring Fhb1 showed significantly elevated D3G/DON abundance ratios. 

PMID- 25775426
TI  - Distinct motor strategies underlying split-belt adaptation in human walking and
      running.
AB  - The aim of the present study was to elucidate the adaptive and de-adaptive nature
      of human running on a split-belt treadmill. The degree of adaptation and de
      adaptation was compared with those in walking by calculating the antero-posterior
      component of the ground reaction force (GRF). Adaptation to walking and running
      on a split-belt resulted in a prominent asymmetry in the movement pattern upon
      return to the normal belt condition, while the two components of the GRF showed
      different behaviors depending on the gaits. The anterior braking component showed
      prominent adaptive and de-adaptive behaviors in both gaits. The posterior
      propulsive component, on the other hand, exhibited such behavior only in running,
      while that in walking showed only short-term aftereffect (lasting less than 10
      seconds) accompanied by largely reactive responses. These results demonstrate a
      possible difference in motor strategies (that is, the use of reactive feedback
      and adaptive feedforward control) by the central nervous system (CNS) for split
      belt locomotor adaptation between walking and running. The present results
      provide basic knowledge on neural control of human walking and running as well as
      possible strategies for gait training in athletic and rehabilitation scenes. 

PMID- 25775427
TI  - Cultivation and differentiation change nuclear localization of chromosome
      centromeres in human mesenchymal stem cells.
AB  - Chromosome arrangement in the interphase nucleus is not accidental. Strong
      evidences support that nuclear localization is an important mechanism of
      epigenetic regulation of gene expression. The purpose of this research was to
      identify differences in the localization of centromeres of chromosomes 6, 12, 18
      and X in human mesenchymal stem cells depending on differentiation and
      cultivating time. We analyzed centromere positions in more than 4000 nuclei in 19
      mesenchymal stem cell cultures before and after prolonged cultivation and after
      differentiation into osteogenic and adipogenic directions. We found a centromere
      reposition of HSAX at late passages and after differentiation in osteogenic
      direction as well as of HSA12 and HSA18 after adipogenic differentiation. The
      observed changes of the nuclear structure are new nuclear characteristics of the
      studied cells which may reflect regulatory changes of gene expression during the
      studied processes. 

PMID- 25775428
TI  - Candidiasis (vulvovaginal).
AB  - INTRODUCTION: Vulvovaginal candidiasis is estimated to be the second most common
      cause of vaginitis after bacterial vaginosis. Candida albicans accounts for 85%
      to 90% of cases. METHODS AND OUTCOMES: We conducted a systematic review and aimed
      to answer the following clinical questions: What are the effects of drug
      treatments for acute vulvovaginal candidiasis in non-pregnant symptomatic women?
      What are the effects of alternative or complementary treatments for acute
      vulvovaginal candidiasis in non-pregnant symptomatic women? What are the effects
      of treating asymptomatic non-pregnant women with a positive swab for candidiasis?
      We searched: Medline, Embase, The Cochrane Library, and other important databases
      up to October 2013 (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 23 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: alternative or
      complementary treatments; douching; drug treatments; garlic; intravaginal
      preparations (nystatin, imidazoles, tea tree oil); oral fluconazole; oral
      itraconazole; and yoghurt containing Lactobacillus acidophilus (oral or
      intravaginal).

PMID- 25775429
TI  - Imbalance of dendritic cell co-stimulation in COPD.
AB  - BACKGROUND: Dendritic cells (DCs) control immunity and play a role in the
      pathogenesis of chronic obstructive pulmonary disease (COPD). However, the
      expression of function-associated surface molecules on circulating DCs in COPD is
      unknown. METHODS: Four-colour flow cytometry was used to compare blood DC surface
      molecules of 54 patients with COPD (median age: 59 years; median FEV1: 38%
      predicted, median CAT score: 24) with two age-matched control groups with normal
      lung function: 21 current smokers and 21 never-smokers. RESULTS: Concentrations
      of plasmacytoid DCs (pDCs) and myeloid DCs (mDCs) and the mDC/pDC ratio did not
      differ between the groups. The increased expression of BDCA-1, BDCA-3, CD86 and
      CCR5 on mDCs in patients with COPD did not significantly differ from smokers with
      normal lung function. In contrast, COPD was specifically characterised by a
      decreased expression of the anti-inflammatory co-stimulatory molecule PD-L1 on
      pDCs and an increased expression of the pro-inflammatory co-stimulatory molecule
      OX40 ligand (OX40L) on mDCs. These changes were not confined to patients with
      elevated systemic inflammation markers (leukocytes, c-reactive protein,
      interleukin-6, fibrinogen). The ratio of OX40L to PD-L1 expression (OX40L/PD-L1
      ratio), a quantitative measure of imbalanced DC co-stimulation, correlated with
      the severity of pulmonary emphysema in patients with COPD. CONCLUSION: An
      imbalance of DC co-stimulation might contribute to the pathogenesis of COPD.

PMID- 25775431
TI  - Activation of aryl thiocyanates followed by aryne insertion: access to 1,2
      thiobenzonitriles.
AB  - Palladium-catalyzed activation of carbon-sulfur bonds allows aryne insertion into
      aryl thiocyanates to generate new C-SAr and C-CN bonds in one step. The readily
      available starting materials make this method efficient in generating a variety
      of 1,2-thiobenzonitriles. By choosing an oxygen atmosphere the yields are
      increased and side reactions are minimized. 

PMID- 25775430
TI  - Large-scale evolutionary analyses on SecB subunits of bacterial sec system.
AB  - Protein secretion systems are extremely important in bacteria because they are
      involved in many fundamental cellular processes. Of the various secretion
      systems, the Sec system is composed of seven different subunits in bacteria, and
      subunit SecB brings secreted preproteins to subunit SecA, which with SecYEG and
      SecDF forms a complex for the translocation of secreted preproteins through the
      inner membrane. Because of the wide existence of Sec system across bacteria,
      eukaryota, and archaea, each subunit of the Sec system has a complicated
      evolutionary relationship. Until very recently, 5,162 SecB sequences have been
      documented in UniProtKB, however no phylogenetic study has been conducted on a
      large sampling of SecBs from bacterial Sec secretion system, and no statistical
      study has been conducted on such size of SecBs in order to exhaustively
      investigate their variances of pairwise p-distance along taxonomic lineage from
      kingdom to phylum, to class, to order, to family, to genus and to organism. To
      fill in these knowledge gaps, 3,813 bacterial SecB sequences with full taxonomic
      lineage from kingdom to organism covering 4 phyla, 11 classes, 41 orders, 82
      families, 269 genera, and 3,744 organisms were studied. Phylogenetic analysis
      revealed how the SecBs evolved without compromising their function with examples
      of 3-D structure comparison of two SecBs from Proteobacteria, and possible
      factors that affected the SecB evolution were considered. The average pairwise p
      distances showed that the variance varied greatly in each taxonomic group.
      Finally, the variance was further partitioned into inter- and intra-clan
      variances, which could correspond to vertical and horizontal gene transfers, with
      relevance for Achromobacter, Brevundimonas, Ochrobactrum, and Pseudoxanthomonas. 

PMID- 25775432
TI  - ERK phosphorylation and miR-181a expression modulate activation of human memory
      TH17 cells.
AB  - T helper (TH) cell polarization during priming is modulated by a number of
      signals, but whether polarization to a given phenotype also influences recall
      responses of memory TH cells is relatively unknown. Here we show that miR-181a is
      selectively induced in both human and mouse naive T cells differentiating into
      the TH17, but not TH1 or TH2 subset. In human memory TH17 cells, miR-181a
      regulates responses to cognate antigens through modulation of ERK
      phosphorylation. By enhancing the signalling cascade from the T-cell receptor,
      such molecular network reduces the threshold of TH17 cell activation. Moreover,
      at a late time point, the same network induces a self-regulatory mechanism
      dependent on ID3, a negative regulator of transcription factors that control RORC
      expression, thus modulating TH17 activity. Our results demonstrate that the
      phenotype acquired by TH cells during priming contributes to their threshold of
      activation to secondary antigenic stimulations, thus influencing memory
      responses. 

PMID- 25775433
TI  - Repulsive axon guidance by Draxin is mediated by protein Kinase B (Akt), glycogen
      synthase kinase-3beta (GSK-3beta) and microtubule-associated protein 1B.
AB  - Draxin is an important axon guidance cue necessary for the formation of forebrain
      commissures including the corpus callosum, but the molecular details of draxin
      signaling are unknown. To unravel how draxin signals are propagated we used
      murine cortical neurons and genetic and pharmacological approaches. We found that
      draxin-induced growth cone collapse critically depends on draxin receptors
      (deleted in colorectal cancer, DCC), inhibition of protein kinase B/Akt,
      activation of GSK-3beta (glycogen synthase kinase-3beta) and the presence of
      microtubule-associated protein MAP1B. This study, for the first time elucidates
      molecular events in draxin repulsion, links draxin and DCC to MAP1B and
      identifies a novel MAP1B-depenent GSK-3beta pathway essential for chemo-repulsive
      axon guidance cue signaling. 

PMID- 25775434
TI  - Liquid-based iterative recombineering method tolerant to counter-selection
      escapes.
AB  - Selection-based recombineering is a flexible and proven technology to precisely
      modify bacterial genomes at single base resolution. It consists of two steps of
      homologous recombination followed by selection/counter-selection. However, the
      shortage of efficient counter-selectable markers limits the throughput of this
      method. Additionally, the emergence of 'selection escapees' can affect
      recombinant pools generated through this method, and they must be manually
      removed at each step of selection-based recombineering. Here, we report a series
      of efforts to improve the throughput and robustness of selection-based
      recombineering and to achieve seamless and automatable genome engineering. Using
      the nucleoside kinase activity of herpes simplex virus thymidine kinase (hsvTK)
      on the non-natural nucleoside dP, a highly efficient, rapid, and liquid-based
      counter-selection system was established. By duplicating hsvtk gene, combined
      with careful control of the population size for the subsequent round, we
      effectively eliminated selection escapes, enabling seamless and multiple
      insertions/replacement of gene-size fragments in the chromosome. Four rounds of
      recombineering could thus be completed in 10 days, requiring only liquid handling
      and without any need for colony isolation or genotype confirmation. The
      simplicity and robustness of our method make it broadly accessible for multi
      locus chromosomal modifications. 

PMID- 25775435
TI  - D-cycloserine enhances generalization of fear extinction in children.
AB  - BACKGROUND: For exposure therapy to be successful, it is essential that fear
      extinction learning extends beyond the treatment setting. D-cycloserine (DCS) may
      facilitate treatment gains by increasing generalization of extinction learning,
      however, its effects have not been tested in children. We examined whether DCS
      enhanced generalization of fear extinction learning across different stimuli and
      contexts among children with specific phobias. METHODS: The study was a double
      blind placebo-controlled randomized controlled trial among dog or spider phobic
      children aged 6-14. Participants ingested either 50 mg of DCS (n = 18) or placebo
      (n = 17) before receiving a single prolonged exposure session to their feared
      stimulus. Return of fear was examined 1 week later to a different stimulus (a
      different dog or spider), presented in both the original treatment context and an
      alternate context. Avoidance and fear were measured with Behavior Approach Tests
      (BATs), where the child was asked to increase proximity to the stimulus while
      reporting their fear level. RESULTS: There were no differences in BAT performance
      between groups during the exposure session or when a new stimulus was later
      presented in the treatment context. However, when the new stimulus was presented
      in a different context, relative to placebo, the DCS group showed less avoidance
      (P = .03) and less increase in fear (P = .04) with moderate effect sizes.
      CONCLUSIONS: DCS enabled children to better retain their fear extinction
      learning. This new learning generalized to different stimuli and contexts.

PMID- 25775436
TI  - Rationale for the evaluation of fluoxetine in the treatment of enterovirus D68
      associated acute flaccid myelitis.

PMID- 25775437
TI  - Relationships of neurosensory disorders and reduced work ability to alternative
      frequency weightings of hand-transmitted vibration.
AB  - OBJECTIVE: This cohort study aims to compare the performance of alternative
      frequency weightings of hand-transmitted vibration (HTV) for the assessment of
      the exposure-response relationships for neurosensory disorders and reduced work
      ability among HTV-exposed workers. METHODS: In a 3-year follow up study, the
      occurrence of neurosensory symptoms and reduced work ability, and the response to
      quantitative sensory testing (grip force, manipulative dexterity, touch
      sensation) were investigated in 249 HTV-exposed workers and 138 healthy controls.
      Among the HTV-exposed workers, the sensory outcomes were related to measures of
      daily vibration exposure expressed in terms of 8-hour energy-equivalent frequency
      weighted acceleration magnitude [A(8)]. To calculate A(8), the acceleration
      magnitudes of vibration were weighted by means of four alternative frequency
      weightings of HTV. RESULTS: The occurrence of neurosensory symptoms, reduced work
      ability, and abnormalities of sensory tests was greater among the HTV-exposed
      workers than the controls. Among the HTV-exposed workers, the deterioration of
      neurosensory outcomes and the reduction of work ability increased on par with the
      measures of vibration exposure. Exposure-response models revealed that the four
      alternative frequency weightings of HTV provided the same predictions for the
      probability of finger numbness among the exposed workers (observed 36% versus
      predicted 32%). CONCLUSIONS: The findings of this study revealed significant dose
      response relationships between measures of vibration exposure, sensory disorders,
      and reduced work ability among the HTV-exposed workers. There were no differences
      in the prediction of finger numbness between measures of vibration exposure
      calculated with alternative frequency weightings of HTV.

PMID- 25775438
TI  - Group prenatal care: has its time come?
AB  - Group prenatal care is an emerging trend in obstetrics, and for medically low
      risk women has been shown to result in lower rates of preterm birth, higher rates
      of breastfeeding, and higher rates of participation in postpartum family
      planning. Significant cost savings to the health care system are seen when the
      lower rates of preterm birth and neonatal intensive care unit admissions are
      considered. More research is needed about patients' health outcomes as well as
      the economic and workforce implications to outpatient obstetric practices before
      widely transitioning prenatal care into group settings. 

PMID- 25775439
TI  - Women's Health in the Age of Patient Protection and the Affordable Care Act.
AB  - The Patient Protection and Affordable Care Act of 2010 is the most sweeping
      health care legislation in a generation. The goal of the legislation is to
      increase access to both public and private insurance, and to improve the
      affordability and quality of care. Many provisions of the bill have a direct
      impact on the women's health care services. This paper provides an overview of
      the bill's provisions that have the largest impact on women's health care and
      provides data on the impact of the bill to date. 

PMID- 25775441
TI  - Trajectories of change during a randomized controlled trial of internet-delivered
      psychological treatment for adolescent chronic pain: how does change in pain and
      function relate?
AB  - Although pain and function improve at immediate posttreatment for youth receiving
      cognitive behavioral therapy for chronic pain, limited data are available to
      understand changes that youth make during psychological treatment. We sought to
      characterize distinct trajectory patterns of change in pain and function to
      understand the temporal association of these changes during internet-delivered
      cognitive behavioral therapy (CBT). Weekly repeated assessments of pain and
      function were conducted during 8 weeks of treatment among 135 adolescents, aged
      11 to 17 years, with chronic pain who were randomized to the cognitive behavioral
      intervention arm of an ongoing trial of internet-delivered CBT (Web-based
      management of adolescent pain; Web-MAP2). Using random-effects growth mixture
      models, we characterized pain and functional disability trajectories finding
      distinct trajectory groups indicating patterns of both linear and quadratic
      effects. Trajectories of change showed that some patients' pain and functional
      disability were improving, others worsened or changed minimally. Paired t tests
      compared the within-subject relative change rate in pain and function
      demonstrating similar change range for pain and function during the treatment
      period. There was no support for improvements in either pain or function to
      precede changes in the other domain. Findings may be useful in informing future
      studies of psychosocial treatments for pediatric chronic pain to consider how to
      target treatment strategies to distinct patient response profiles. This may lead
      to the development of intervention strategies that can both more effectively
      target children's pain and function during treatment and lead to sustained
      changes after treatment. 

PMID- 25775440
TI  - Caring for Opioid-dependent Pregnant Women: Prenatal and Postpartum Care
      Considerations.
AB  - Pregnancy is an opportune time to identify opioid dependence, facilitate
      conversion to opioid maintenance treatment, and coordinate care with specialists
      in addiction medicine, behavioral health, and social services. Comprehensive
      prenatal care for opioid-dependent women involves the evaluation and the
      management of co-occurring psychiatric disorders, polysubstance use, infectious
      diseases, social stressors, and counseling regarding the importance of
      breastfeeding, contraception, and neonatal abstinence syndrome. Although the
      complex psychiatric, social, and environmental factors faced by this population
      pose significant challenges to obstetric care providers, the development of
      strong patient-provider relationships can facilitate the ability to deliver
      efficient and effective health care during pregnancy. 

PMID- 25775442
TI  - Preoperative ultrasound and photoacoustic imaging of nonmelanoma skin cancers.

PMID- 25775443
TI  - Successful treatment of a large solitary nasal tip trichoepithelioma using the
      10,600-nm carbon dioxide laser.

PMID- 25775444
TI  - Catastrophic eruptive keratoacanthomas and squamous cell cancers after treatment
      with an FLT3 inhibitor quizartinib (AC220).

PMID- 25775445
TI  - Effect of a second injection of botulinum toxin on lower facial contouring, as
      evaluated using 3-dimensional laser scanning.
AB  - BACKGROUND: Botulinum toxin type A (BoNT-A) is widely used to improve the lower
      facial contour. OBJECTIVE: To determine the difference in the changes in the
      lower facial contour achieved with 1 and 2 sessions of BoNT-A injections using 3
      dimensional (3D) laser scanning. MATERIALS AND METHODS: Twenty volunteers were
      randomly divided into 2 groups. Group I (n = 10) received a single injection,
      whereas Group II (n = 10) received 2 sessions of injections, the second being
      administered 4 months after the first. Each injection comprised of 25 U of BoNT-A
      and was administered to the masseter muscle bilaterally. Evaluation of the effect
      of BoNT-A injection was performed using 3D laser scan images obtained before the
      injection and 6 months thereafter in Group I, and before the first injection and
      6 months thereafter in the Group II. RESULTS: The mean changes in the volume and
      thickness in Group I were -1,186 mm and -1.52 mm, respectively; the corresponding
      changes were -4,072 mm and -3.84 mm in Group II. The reductions were
      significantly greater in Group II than in Group I. CONCLUSION: The administration
      of a second BoNT-A injection is effective for better aesthetic results for the
      lower facial contour.

PMID- 25775446
TI  - Imaging of desmoplastic trichoepithelioma by high-definition optical coherence
      tomography.

PMID- 25775447
TI  - Treatment of segmental keratosis follicularis (Darier disease) using ablative
      fractional laser resurfacing.

PMID- 25775448
TI  - On the firing rate dependency of the phase response curve of rat Purkinje neurons
      in vitro.
AB  - Synchronous spiking during cerebellar tasks has been observed across Purkinje
      cells: however, little is known about the intrinsic cellular mechanisms
      responsible for its initiation, cessation and stability. The Phase Response Curve
      (PRC), a simple input-output characterization of single cells, can provide
      insights into individual and collective properties of neurons and networks, by
      quantifying the impact of an infinitesimal depolarizing current pulse on the time
      of occurrence of subsequent action potentials, while a neuron is firing
      tonically. Recently, the PRC theory applied to cerebellar Purkinje cells revealed
      that these behave as phase-independent integrators at low firing rates, and
      switch to a phase-dependent mode at high rates. Given the implications for
      computation and information processing in the cerebellum and the possible role of
      synchrony in the communication with its post-synaptic targets, we further
      explored the firing rate dependency of the PRC in Purkinje cells. We isolated key
      factors for the experimental estimation of the PRC and developed a closed-loop
      approach to reliably compute the PRC across diverse firing rates in the same
      cell. Our results show unambiguously that the PRC of individual Purkinje cells is
      firing rate dependent and that it smoothly transitions from phase independent
      integrator to a phase dependent mode. Using computational models we show that
      neither channel noise nor a realistic cell morphology are responsible for the
      rate dependent shift in the phase response curve. 

PMID- 25775450
TI  - Correction: exome sequencing reveals novel and recurrent mutations with clinical
      significance in inherited retinal dystrophies.

PMID- 25775449
TI  - Effect of dopaminergic D1 receptors on plasticity is dependent of serotoninergic
      5-HT1A receptors in L5-pyramidal neurons of the prefrontal cortex.
AB  - Major depression and schizophrenia are associated with dysfunctions of
      serotoninergic and dopaminergic systems mainly in the prefrontal cortex (PFC).
      Both serotonin and dopamine are known to modulate synaptic plasticity. 5-HT1A
      receptors (5-HT1ARs) and dopaminergic type D1 receptors are highly represented on
      dendritic spines of layer 5 pyramidal neurons (L5PyNs) in PFC. How these
      receptors interact to tune plasticity is poorly understood. Here we show that D1
      like receptors (D1Rs) activation requires functional 5HT1ARs to facilitate LTP
      induction at the expense of LTD. Using 129/Sv and 5-HT1AR-KO mice, we recorded
      post-synaptic currents evoked by electrical stimulation in layer 2/3 after
      activation or inhibition of D1Rs. High frequency stimulation resulted in the
      induction of LTP, LTD or no plasticity. The D1 agonist markedly enhanced the NMDA
      current in 129/Sv mice and the percentage of L5PyNs displaying LTP was enhanced
      whereas LTD was reduced. In 5-HT1AR-KO mice, the D1 agonist failed to increase
      the NMDA current and orientated the plasticity towards L5PyNs displaying LTD,
      thus revealing a prominent role of 5-HT1ARs in dopamine-induced modulation of
      plasticity. Our data suggest that in pathological situation where 5-HT1ARs
      expression varies, dopaminergic treatment used for its ability to increase LTP
      could turn to be less and less effective. 

PMID- 25775451
TI  - The epidemic of HIV, syphilis, chlamydia and gonorrhea and the correlates of
      sexual transmitted infections among men who have sex with men in Jiangsu, China,
      2009.
AB  - BACKGROUND: In China, the HIV/AIDS epidemic is expanding among men who have sex
      with men (MSM). As independent risk factors of HIV infection, the epidemics of
      Chlamydia (CT) and Gonorrhea (NG) in MSM were not well studied, particular for
      the risk factors of these infectious. The objectives of current reported study
      were to understand the dynamics of HIV and other sexual transmitted infections
      (STIs) among MSM in Jiangsu, China, and to measure factors that correlated with
      STIs. METHODS: In order to gain more participants, a multisite cross-sectional
      study design was used in our study, by using convenience-sampling to recruit MSM
      in two Changzhou and Yangzhou, Jiangsu, China, between the July and October of
      2009. RESULTS: In this comprehensive survey involving MSM in two cities of
      Jiangsu province of China, the prevalence of STIs of CT (6.54%), NG (3.63%),
      syphilis (20.34%) and HIV (11.62%) were measured. Overall, the STIs prevalence
      (CT, NG or syphilis) for the participants in our study was 26.39%, meanwhile,
      3.4% (14 out of the 413) participants had at least two kinds of STIs. Meeting
      casual partners at parks, public restrooms or other public areas, having had anal
      sex with men in the past six months, having had STI symptoms in the past year
      were positively correlated with STIs positive, with adjusted ORs of 4.61(95%CI
      1.03-20.75), 1.91(95%CI 1.14-3.21) and 2.36(95%CI 1.07,5.24). CONCLUSION: Our
      study findings reiterate the fact that Chinese MSM are highly susceptible to
      acquiring syphilis, CT, NG and HIV, and there is an urgent need for intervention
      targeted towards this population. Behavioral measures should constitute an
      important part of the targeted intervention. Furthermore, the already implemented
      preventive and diagnostic services for HIV should be expanded to include syphilis
      CT and NG, too.

PMID- 25775452
TI  - Combinational reasoning of quantitative fuzzy topological relations for simple
      fuzzy regions.
AB  - In recent years, formalization and reasoning of topological relations have become
      a hot topic as a means to generate knowledge about the relations between spatial
      objects at the conceptual and geometrical levels. These mechanisms have been
      widely used in spatial data query, spatial data mining, evaluation of equivalence
      and similarity in a spatial scene, as well as for consistency assessment of the
      topological relations of multi-resolution spatial databases. The concept of
      computational fuzzy topological space is applied to simple fuzzy regions to
      efficiently and more accurately solve fuzzy topological relations. Thus,
      extending the existing research and improving upon the previous work, this paper
      presents a new method to describe fuzzy topological relations between simple
      spatial regions in Geographic Information Sciences (GIS) and Artificial
      Intelligence (AI). Firstly, we propose a new definition for simple fuzzy line
      segments and simple fuzzy regions based on the computational fuzzy topology. And
      then, based on the new definitions, we also propose a new combinational reasoning
      method to compute the topological relations between simple fuzzy regions,
      moreover, this study has discovered that there are (1) 23 different topological
      relations between a simple crisp region and a simple fuzzy region; (2) 152
      different topological relations between two simple fuzzy regions. In the end, we
      have discussed some examples to demonstrate the validity of the new method,
      through comparisons with existing fuzzy models, we showed that the proposed
      method can compute more than the existing models, as it is more expressive than
      the existing fuzzy models. 

PMID- 25775453
TI  - Ablation of tumor necrosis factor is associated with decreased inflammation and
      alterations of the microbiota in a mouse model of inflammatory bowel disease.
AB  - Inflammatory bowel disease (IBD) is associated with prolonged, excess secretions
      of Tumor Necrosis Factor (TNF). Many patients with IBD have successful management
      of IBD symptoms by blocking TNF secretion or signaling. However, some patients
      are non-responsive to this therapy, eventually become refractory to therapy, or
      may develop harmful side-effects [corrected]. Alterations in the microbiota that
      are associated with the lack of TNF could be a contributing cause of this
      therapeutic insufficiency seen in some patients. Here we use wildtype (WT) and
      mice lacking Tnf (Tnf-/-) in an acute TNBS colitis model to investigate the role
      of TNF in colitis and how its presence or absence affects the colonic microbiota.
      As expected, Tnf-/- had less severe inflammation than WT mice. Microbiome
      analysis revealed significant Tnf dependent-differences in alpha and beta
      diversity. There were also notable differences in many species that were also
      primarily Tnf dependent. Taken together, our data indicates that TNF contributes
      significantly to the inflammation and microbiotal alterations in that occur in
      IBD.

PMID- 25775454
TI  - The effect of socioeconomic indicators and macronutrient intake rate on body
      composition in adolescents 12 to 16 years old in Merida, Yucatan.
AB  - Intake pattern of macronutrients (protein, lipid, carbohydrate) and socioeconomic
      status (SES) are major causes of high child and adolescent overweight and obesity
      prevalences in Mexico. An evaluation was done of the relationship between body
      mass index (BMI)-based nutritional status and body composition (BC),
      macronutrient intake rates (MIR) and SES indicators in 127 boys and 156 girls
      aged 12 to 16 years attending schools in Merida, Mexico. Anthropometric variables
      included height, weight, and BMI. The BC (body fat mass, fat-free mass, dry lean
      mass) was estimated by bioelectrical impedance (Bodystat 1500 MDD). The MIR were
      estimated following FAO/WHO/UNO standard (1985). Proxy socioeconomic indicators
      included parents' age (as a maturity indicator) and education, fathers'
      occupation, school type and monthly household food expenditure per capita. Excess
      weight (overweight + obesity) assessed by BMI, was higher in boys (40.16 %) than
      in girls (33.97 %). Boys had higher BMI, less fat mass and higher fat-free mass
      than girls. The MIR did not vary significantly in response to age, sex, BC or
      SES. Participants with higher SES were taller and heavier, had higher fat-free
      mass and lower fat mass. In the studied adolescents, anthropometric and BC
      values, and overweight and obesity rates were more associated with SES than MIR.

PMID- 25775456
TI  - Investigation of retinal morphology alterations using spectral domain optical
      coherence tomography in a mouse model of retinal branch and central retinal vein
      occlusion.
AB  - Retinal vein occlusion is a leading cause of visual impairment. Experimental
      models of this condition based on laser photocoagulation of retinal veins have
      been described and extensively exploited in mammals and larger rodents such as
      the rat. However, few reports exist on the use of this paradigm in the mouse. The
      objective of this study was to investigate a model of branch and central retinal
      vein occlusion in the mouse and characterize in vivo longitudinal retinal
      morphology alterations using spectral domain optical coherence tomography.
      Retinal veins were experimentally occluded using laser photocoagulation after
      intravenous application of Rose Bengal, a photo-activator dye enhancing thrombus
      formation. Depending on the number of veins occluded, variable amounts of
      capillary dropout were seen on fluorescein angiography. Vascular endothelial
      growth factor levels were markedly elevated early and peaked at day one. Retinal
      thickness measurements with spectral domain optical coherence tomography showed
      significant swelling (p<0.001) compared to baseline, followed by gradual thinning
      plateauing two weeks after the experimental intervention (p<0.001). Histological
      findings at day seven correlated with spectral domain optical coherence
      tomography imaging. The inner layers were predominantly affected by degeneration
      with the outer nuclear layer and the photoreceptor outer segments largely
      preserved. The application of this retinal vein occlusion model in the mouse
      carries several advantages over its use in other larger species, such as access
      to a vast range of genetically modified animals. Retinal changes after
      experimental retinal vein occlusion in this mouse model can be non-invasively
      quantified by spectral domain optical coherence tomography, and may be used to
      monitor effects of potential therapeutic interventions. 

PMID- 25775455
TI  - Is quality and completeness of reporting of systematic reviews and meta-analyses
      published in high impact radiology journals associated with citation rates?
AB  - PURPOSE: The purpose of this study is to determine whether study quality and
      completeness of reporting of systematic reviews (SR) and meta-analyses (MA)
      published in high impact factor (IF) radiology journals is associated with
      citation rates. METHODS: All SR and MA published in English between Jan 2007-Dec
      2011, in radiology journals with an IF >2.75, were identified on Ovid MEDLINE.
      The Assessing the Methodologic Quality of Systematic Reviews (AMSTAR) checklist
      for study quality, and the Preferred Reporting Items for Systematic Reviews and
      Meta-Analyses (PRISMA) checklist for study completeness, was applied to each SR &
      MA. Each SR & MA was then searched in Google Scholar to yield a citation rate.
      Spearman correlation coefficients were used to assess the relationship between
      AMSTAR and PRISMA results with citation rate. Multivariate analyses were
      performed to account for the effect of journal IF and journal 5-year IF on
      correlation with citation rate. Values were reported as medians with
      interquartile range (IQR) provided. RESULTS: 129 studies from 11 journals were
      included (50 SR and 79 MA). Median AMSTAR result was 8.0/11 (IQR: 5-9) and median
      PRISMA result was 23.0/27 (IQR: 21-25). The median citation rate for SR & MA was
      0.73 citations/month post-publication (IQR: 0.40-1.17). There was a positive
      correlation between both AMSTAR and PRISMA results and SR & MA citation rate;
      rho=0.323 (P=0.0002) and rho=0.327 (P=0.0002) respectively. Positive correlation
      persisted for AMSTAR and PRISMA results after journal IF was partialed out;
      rho=0.243 (P=0.006) and rho=0.256 (P=0.004), and after journal 5-year IF was
      partialed out; rho=0.235 (P=0.008) and rho=0.243 (P=0.006) respectively.
      CONCLUSION: There is a positive correlation between the quality and the
      completeness of a reported SR or MA with citation rate which persists when
      adjusted for journal IF and journal 5-year IF.

PMID- 25775457
TI  - The relative contribution of immigration or local increase for persistence of
      urban schistosomiasis in Salvador, Bahia, Brazil.
AB  - Urbanization is increasing across the globe, and diseases once considered rural
      can now be found in urban areas due to the migration of populations from rural
      endemic areas, local transmission within the city, or a combination of factors.
      We investigated the epidemiologic characteristics of urban immigrants and natives
      living in a neighborhood of Salvador, Brazil where there is a focus of
      transmission of Schistosoma mansoni. In a cross-sectional study, all inhabitants
      from 3 sections of the community were interviewed and examined. In order to
      determine the degree of parasite differentiation between immigrants and the
      native born, S. mansoni eggs from stools were genotyped for 15 microsatellite
      markers. The area received migrants from all over the state, but most infected
      children had never been outside of the city, and infected snails were present at
      water contact sites. Other epidemiologic features suggested immigration
      contributed little to the presence of infection. The intensity and prevalence of
      infection were the same for immigrants and natives when adjusted for age, and
      length of immigrant residence in the community was positively associated with
      prevalence of infection. The population structure of the parasites also supported
      that the contribution from immigration was small, since the host-to-host
      differentiation was no greater in the urban parasite population than a rural
      population with little distant immigration, and there had been little
      differentiation in the urban population over the past 7 years. Public health
      efforts should focus on eliminating local transmission, and once eliminated,
      reintroduction from distant migration is unlikely. 

PMID- 25775458
TI  - Sex-specific differences in agonistic behaviour, sound production and auditory
      sensitivity in the callichthyid armoured catfish Megalechis thoracata.
AB  - BACKGROUND: Data on sex-specific differences in sound production, acoustic
      behaviour and hearing abilities in fishes are rare. Representatives of numerous
      catfish families are known to produce sounds in agonistic contexts (intraspecific
      aggression and interspecific disturbance situations) using their pectoral fins.
      The present study investigates differences in agonistic behaviour, sound
      production and hearing abilities in males and females of a callichthyid catfish.
      METHODOLOGY/PRINCIPAL FINDINGS: Eight males and nine females of the armoured
      catfish Megalechis thoracata were investigated. Agonistic behaviour displayed
      during male-male and female-female dyadic contests and sounds emitted were
      recorded, sound characteristics analysed and hearing thresholds measured using
      the auditory evoked potential (AEP) recording technique. Male pectoral spines
      were on average 1.7-fold longer than those of same-sized females. Visual and
      acoustic threat displays differed between sexes. Males produced low-frequency
      harmonic barks at longer distances and thumps at close distances, whereas females
      emitted broad-band pulsed crackles when close to each other. Female aggressive
      sounds were significantly shorter than those of males (167 ms versus 219 to 240
      ms) and of higher dominant frequency (562 Hz versus 132 to 403 Hz). Sound
      duration and sound level were positively correlated with body and pectoral spine
      length, but dominant frequency was inversely correlated only to spine length.
      Both sexes showed a similar U-shaped hearing curve with lowest thresholds between
      0.2 and 1 kHz and a drop in sensitivity above 1 kHz. The main energies of sounds
      were located at the most sensitive frequencies. CONCLUSIONS/SIGNIFICANCE: Current
      data demonstrate that both male and female M. thoracata produce aggressive
      sounds, but the behavioural contexts and sound characteristics differ between
      sexes. Sexes do not differ in hearing, but it remains to be clarified if this is
      a general pattern among fish. This is the first study to describe sex-specific
      differences in agonistic behaviour in fishes.

PMID- 25775459
TI  - Connecting proline and gamma-aminobutyric acid in stressed plants through non
      enzymatic reactions.
AB  - The accumulation of proline (Pro) in plants exposed to biotic/abiotic stress is a
      well-documented and conserved response in most vegetal species. Stress conditions
      induce the overproduction of reactive oxygen species which can lead to cellular
      damage. In vitro assays have shown that enzyme inactivation by hydroxyl radicals
      (.OH) can be avoided in presence of Pro, suggesting that this amino acid could
      act as an .OH scavenger. We applied Density Functional Theory coupled with a
      polarizable continuum model to elucidate how Pro reacts with .OH. In this work we
      suggest that Pro reacts favourably with .OH by H-abstraction on the amine group.
      This reaction produces the spontaneous decarboxylation of Pro leading to the
      formation of pyrrolidin-1-yl. In turn, pyrrolidin-1-yl can easily be converted to
      Delta1-pyrroline, the substrate of the enzyme Delta1-pyrroline dehydrogenase,
      which produces gamma-aminobutyric acid (GABA). GABA and Pro are frequently
      accumulated in stressed plants and several protective roles have been assigned to
      these molecules. Thereby we present an alternative non-enzymatic way to
      synthetize GABA under oxidative stress. Finally this work sheds light on a new
      beneficial role of Pro accumulation in the maintenance of photosynthetic
      activity. 

PMID- 25775461
TI  - Correction: altered astrocytic swelling in the cortex of alpha-syntrophin
      negative GFAP/EGFP mice.

PMID- 25775460
TI  - Periostin accelerates bone healing mediated by human mesenchymal stem cell
      embedded hydroxyapatite/tricalcium phosphate scaffold.
AB  - BACKGROUND: Periostin, an extracellular matrix protein, is expressed in bone,
      more specifically, the periosteum and periodontal ligaments, and plays a key role
      in formation and metabolism of bone tissues. Human adipose tissue-derived
      mesenchymal stem cells (hASCs) have been reported to differentiate into
      osteoblasts and stimulate bone repair. However, the role of periostin in hASC
      mediated bone healing has not been clarified. In the current study, we examined
      the effect of periostin on bone healing capacity of hASCs in a critical size
      calvarial defect model. METHODS AND RESULTS: Recombinant periostin protein
      stimulated migration, adhesion, and proliferation of hASCs in vitro. Implantation
      of either hASCs or periostin resulted in slight, but not significant, stimulation
      of bone healing, whereas co-implantation of hASCs together with periostin further
      potentiated bone healing. In addition, the number of Ki67-positive proliferating
      cells was significantly increased in calvarial defects by co-implantation of both
      hASCs and periostin. Consistently, proliferation of administered hASCs was
      stimulated by co-implantation with periostin in vivo. In addition, co-delivery of
      hASCs with periostin resulted in markedly increased numbers of CD31-positive
      endothelial cells and alpha-SMA-positive arterioles in calvarial defects.
      CONCLUSIONS: These results suggest that recombinant periostin potentiates hASC
      mediated bone healing by stimulating proliferation of transplanted hASCs and
      angiogenesis in calvarial defects.

PMID- 25775462
TI  - Circadian rhythm genes CLOCK and PER3 polymorphisms and morning gastric motility
      in humans.
AB  - BACKGROUND: Clock genes regulate circadian rhythm and are involved in various
      physiological processes, including digestion. We therefore investigated the
      association between the CLOCK 3111T/C single nucleotide polymorphism and the
      Period3 (PER3) variable-number tandem-repeat polymorphism (either 4 or 5 repeats
      54 nt in length) with morning gastric motility. METHODS: Lifestyle questionnaires
      and anthropometric measurements were performed with 173 female volunteers (mean
      age, 19.4 years). Gastric motility, evaluated by electrogastrography (EGG), blood
      pressure, and heart rate levels were measured at 8:30 a.m. after an overnight
      fast. For gastric motility, the spectral powers (% normal power) and dominant
      frequency (DF, peak of the power spectrum) of the EGG were evaluated. The CLOCK
      and PER3 polymorphisms were determined by polymerase chain reaction (PCR)
      restriction fragment length polymorphism analysis. RESULTS: Subjects with the
      CLOCK C allele (T/C or C/C genotypes: n = 59) showed a significantly lower DF
      (mean, 2.56 cpm) than those with the T/T genotype (n = 114, 2.81 cpm, P < 0.05).
      Subjects with the longer PER3 allele (PER34/5 or PER35/5 genotypes: n = 65) also
      showed a significantly lower DF (2.55 cpm) than those with the shorter PER34/4
      genotype (n = 108, 2.83 cpm, P < 0.05). Furthermore, subjects with both the T/C
      or C/C and PER34/5 or PER35/5 genotypes showed a significantly lower DF (2.43
      cpm, P < 0.05) than subjects with other combinations of the alleles (T/T and
      PER34/4 genotype, T/C or C/C and PER34/4 genotypes, and T/T and PER34/5 or
      PER35/5 genotypes). CONCLUSIONS: These results suggest that minor polymorphisms
      of the circadian rhythm genes CLOCK and PER3 may be associated with poor morning
      gastric motility, and may have a combinatorial effect. The present findings may
      offer a new viewpoint on the role of circadian rhythm genes on the peripheral
      circadian systems, including the time-keeping function of the gut.

PMID- 25775463
TI  - Clostridium difficile infection seasonality: patterns across hemispheres and
      continents - a systematic review.
AB  - BACKGROUND: Studies have demonstrated seasonal variability in rates of
      Clostridium difficile infection (CDI). Synthesising all available information on
      seasonality is a necessary step in identifying large-scale epidemiological
      patterns and elucidating underlying causes. METHODS: Three medical and life
      sciences publication databases were searched from inception to October 2014 for
      longitudinal epidemiological studies written in English, Spanish or Portuguese
      that reported the incidence of CDI. The monthly frequency of CDI were extracted,
      standardized and weighted according to the number of follow-up months. Cross
      correlation coefficients (XCORR) were calculated to examine the correlation and
      lag between the year-month frequencies of reported CDI across hemispheres and
      continents. RESULTS: The search identified 13, 5 and 2 studies from North
      America, Europe, and Oceania, respectively that met the inclusion criteria. CDI
      had a similar seasonal pattern in the Northern and Southern Hemisphere
      characterized by a peak in spring and lower frequencies of CDI in summer/autumn
      with a lag of 8 months (XCORR = 0.60) between hemispheres. There was no
      difference between the seasonal patterns across European and North American
      countries. CONCLUSION: CDI demonstrates a distinct seasonal pattern that is
      consistent across North America, Europe and Oceania. Further studies are required
      to identify the driving factors of the observed seasonality.

PMID- 25775464
TI  - Resources alter the structure and increase stochasticity in bromeliad microfauna
      communities.
AB  - Although stochastic and deterministic processes have been found to jointly shape
      structure of natural communities, the relative importance of both forces may vary
      across different environmental conditions and across levels of biological
      organization. We tested the effects of abiotic environmental conditions, altered
      trophic interactions and dispersal limitation on the structure of aquatic
      microfauna communities in Costa Rican tank bromeliads. Our approach combined
      natural gradients in environmental conditions with experimental manipulations of
      bottom-up interactions (resources), top-down interactions (predators) and
      dispersal at two spatial scales in the field. We found that resource addition
      strongly increased the abundance and reduced the richness of microfauna
      communities. Community composition shifted in a predictable way towards
      assemblages dominated by flagellates and ciliates but with lower abundance and
      richness of algae and amoebae. While all functional groups responded strongly and
      predictably to resource addition, similarity among communities at the species
      level decreased, suggesting a role of stochasticity in species-level assembly
      processes. Dispersal limitation did not affect the communities. Since our design
      excluded potential priority effects we can attribute the differences in community
      similarity to increased demographic stochasticity of resource-enriched
      communities related to erratic changes in population sizes of some species. In
      contrast to resources, predators and environmental conditions had negligible
      effects on community structure. Our results demonstrate that bromeliad microfauna
      communities are strongly controlled by bottom-up forces. They further suggest
      that the relative importance of stochasticity may change with productivity and
      with the organizational level at which communities are examined. 

PMID- 25775465
TI  - The role of Na+/K+-ATPase during chick skeletal myogenesis.
AB  - The formation of a vertebrate skeletal muscle fiber involves a series of
      sequential and interdependent events that occurs during embryogenesis. One of
      these events is myoblast fusion which has been widely studied, yet not completely
      understood. It was previously shown that during myoblast fusion there is an
      increase in the expression of Na+/K+-ATPase. This fact prompted us to search for
      a role of the enzyme during chick in vitro skeletal myogenesis. Chick myogenic
      cells were treated with the Na+/K+-ATPase inhibitor ouabain in four different
      concentrations (0.01-10 MUM) and analyzed. Our results show that 0.01, 0.1 and 1
      MUM ouabain did not induce changes in cell viability, whereas 10 MUM induced a
      45% decrease. We also observed a reduction in the number and thickness of
      multinucleated myotubes and a decrease in the number of myoblasts after 10 MUM
      ouabain treatment. We tested the involvement of MEK-ERK and p38 signaling
      pathways in the ouabain-induced effects during myogenesis, since both pathways
      have been associated with Na+/K+-ATPase. The MEK-ERK inhibitor U0126 alone did
      not alter cell viability and did not change ouabain effect. The p38 inhibitor
      SB202190 alone or together with 10 MUM ouabain did not alter cell viability. Our
      results show that the 10 MUM ouabain effects in myofiber formation do not involve
      the MEK-ERK or the p38 signaling pathways, and therefore are probably related to
      the pump activity function of the Na+/K+-ATPase. 

PMID- 25775467
TI  - Household demography and early childhood mortality in a rice-farming village in
      Northern Laos.
AB  - This paper extends Alexandr Chayanov's model of changing household demography
      (specifically the ratio of food consumers to food producers) and its influence on
      agricultural behavior so that it includes possible adverse effects of a rising
      ratio on nutritional status and early childhood mortality within the household.
      We apply the model to 35 years' worth of longitudinal demographic and economic
      data collected in the irrigated-rice growing village of Na Savang in northern
      Laos. When appropriate controls are included for other household variables,
      unobserved inter-household heterogeneity, and changes in local conditions and
      national policy over the study period, the analysis suggests that a unit increase
      in the household's consumer/producer ratio induces something like a nine-fold
      increase in the risk of death among household members aged less than five years.
      Monte Carlo simulation studies suggest that this may be an over-estimate but also
      that the effect is probably real and likely to be an important factor in
      household demography. At the very least, the results suggest that Chayanov's
      model still has theoretical relevance and deserves to be revived. 

PMID- 25775466
TI  - Recombinant Pvs48/45 antigen expressed in E. coli generates antibodies that block
      malaria transmission in Anopheles albimanus mosquitoes.
AB  - Transmission of malaria parasites from humans to Anopheles mosquitoes can be
      inhibited by specific antibodies elicited during malaria infection, which target
      surface Plasmodium gametocyte/gamete proteins. Some of these proteins may have
      potential for vaccine development. Pvs48/45 is a P. vivax gametocyte surface
      antigen orthologous to Pfs48/45, which may play a role during parasite
      fertilization and thus has potential for transmission blocking (TB) activity.
      Here we describe the expression of a recombinant Pvs48/45 protein expressed in
      Escherichia coli as a ~60kDa construct which we tested for antigenicity using
      human sera and for its immunogenicity and transmission blocking activity of
      specific anti-mouse and anti-monkey Pvs48/45 antibodies. The protein reacted with
      sera of individuals from malaria-endemic areas and in addition induced specific
      IgG antibody responses in BALB/c mice and Aotus l. griseimembra monkeys. Sera
      from both immunized animal species recognized native P. vivax protein in Western
      blot (WB) and immunofluorescence assays. Moreover, sera from immunized mice and
      monkeys produced significant inhibition of parasite transmission to An. Albimanus
      mosquitoes as shown by membrane feeding assays. Results indicate the presence of
      reactive epitopes in the Pvs48/45 recombinant product that induce antibodies with
      TB activity. Further testing of this protein is ongoing to determine its vaccine
      potential. 

PMID- 25775468
TI  - Differential distribution of Shank and GKAP at the postsynaptic density.
AB  - Shank and GKAP are scaffold proteins and binding partners at the postsynaptic
      density (PSD). The distribution and dynamics of Shank and GKAP were studied in
      dissociated hippocampal cultures by pre-embedding immunogold electron microscopy.
      Antibodies against epitopes containing their respective mutual binding sites were
      used to verify the expected juxtapositioning of Shank and GKAP. If all Shank and
      GKAP molecules at the PSD were bound to each other, the distribution of label for
      the two proteins should coincide. However, labels for the mutual binding sites
      showed significant differences in distribution, with a narrow distribution for
      GKAP located close to the postsynaptic membrane, and a wider distribution for
      Shank extending deeper into the cytoplasm. Upon depolarization with high K+,
      neither the intensity nor distribution of label for GKAP changed, but labeling
      intensity for Shank at the PSD increased to ~150% of controls while the median
      distance of label from postsynaptic membrane increased by 7.5 nm. These results
      indicate a preferential recruitment of Shank to more distal parts of the PSD
      complex. Conversely, upon incubation in Ca2+-free medium containing EGTA, the
      labeling intensity of Shank at the PSD decreased to ~70% of controls and the
      median distance of label from postsynaptic membrane decreased by 9 nm, indicating
      a preferential loss of Shank molecules in more distal parts of the PSD complex.
      These observations identify two pools of Shank at the PSD complex, one relatively
      stable pool, closer to the postsynaptic membrane that can bind to GKAP, and
      another more dynamic pool at a location too far away to bind to GKAP. 

PMID- 25775469
TI  - CRISPR/Cas9 as tool for functional study of genes involved in preimplantation
      embryo development.
AB  - The CRISPR/Cas9 system has proven to be an efficient gene-editing tool for genome
      modification of cells and organisms. However, the applicability and efficiency of
      this system in pig embryos have not been studied in depth. Here, we aimed to
      remove porcine OCT4 function as a model case using the CRISPR/Cas9 system.
      Injection of Cas9 and single-guide RNA (sgRNA) against OCT4 decreased the
      percentages of OCT4-positive embryos to 37-50% of total embryos, while ~100% of
      control embryos exhibited clear OCT4 immunostaining. We assessed the mutation
      status near the guide sequence using polymerase chain reaction (PCR) and DNA
      sequencing, and a portion of blastocysts (20% in exon 2 and 50% in exon 5) had
      insertions/deletions near protospacer-adjacent motifs (PAMs). Different target
      sites had frequent deletions, but different concentrations of sgRNA made no
      impact. OCT4 mRNA levels dramatically decreased at the 8-cell stage, and they
      were barely detectable in blastocysts, while mRNA levels of other genes,
      including NANOG, and CDX2 were not affected. In addition, the combination of two
      sgRNAs led to large-scale deletion (about 1.8 kb) in the same chromosome. Next,
      we injected an enhanced green fluorescent protein (eGFP) vector targeting the
      OCT4 exon with Cas9 and sgRNA to create a knockin. We confirmed eGFP fluorescence
      in blastocysts in the inner cell mass, and also checked the mutation status using
      PCR and DNA sequencing. A significant portion of blastocysts had eGFP sequence
      insertions near PAM sites. The CRISPR/CAS9 system provides a good tool for gene
      functional studies by deleting target genes in the pig. 

PMID- 25775471
TI  - Cardiovascular involvement in connective tissue disease: the role of interstitial
      lung disease.
AB  - OBJECTIVE: The aim of this study was to assess cardiovascular involvement in
      patients with connective tissue disease (CTD), and determine whether interstitial
      lung disease (ILD) in these patients is associated with elevated cardiovascular
      risk. METHODS: This study evaluated a retrospective cohort of 436 CTD patients
      admitted to a large teaching hospital in Zhejiang province, China, along with an
      additional 436 participants of an annual community health screening conducted in
      the physical examination center who served as age- and gender-matched controls.
      Demographic, clinical, serologic and imaging characteristics, as well as
      medications used by each participant were recorded. Cardiovascular involvement
      was defined by uniform criteria. Correlations between clinical/serologic factors
      and cardiovascular involvement were determined by univariate and multivariate
      analyses. RESULTS: CTD patients had a significantly higher cardiovascular
      involvement rate than controls (64.7% vs 23.4%), with higher rates of diabetes,
      hypertension, and hyperlipidemia, elevated systolic and diastolic pressures, C
      reactive protein, total cholesterol, and low-density lipoprotein cholesterol, and
      lower albumin and high-density lipoprotein cholesterol (all p < 0.05).
      Furthermore, CTP patients with cardiovascular involvement were significantly
      older, had higher systolic and diastolic pressures, C-reactive protein, glucose,
      and uric acid, higher rates of diabetes, hypertension, and use of moderate- to
      high-dose glucocorticoids, and longer disease duration compared to patients
      without involvement (all p < 0.05). Moreover, CTD in patients with cardiovascular
      involvement was more likely to be complicated by ILD (p < 0.01), which manifested
      as a higher alveolar inflammation score (p < 0.05). In the multivariate analysis,
      cardiovascular involvement in CTD patients was associated with age, systolic
      pressure, body mass index, uric acid, disease duration > 2 years, use of moderate
      to high-dose glucocorticoids, and ILD with a high alveolar inflammation score.
      CONCLUSION: Cardiovascular involvement is increased in CTD patients, and is
      associated with ILD with a higher alveolar inflammation score. Thus, early-stage
      echocardiography and CT scans should be used to detect potential cardiovascular
      complications in these patients.

PMID- 25775470
TI  - Probing the metabolic network in bloodstream-form Trypanosoma brucei using
      untargeted metabolomics with stable isotope labelled glucose.
AB  - Metabolomics coupled with heavy-atom isotope-labelled glucose has been used to
      probe the metabolic pathways active in cultured bloodstream form trypomastigotes
      of Trypanosoma brucei, a parasite responsible for human African trypanosomiasis.
      Glucose enters many branches of metabolism beyond glycolysis, which has been
      widely held to be the sole route of glucose metabolism. Whilst pyruvate is the
      major end-product of glucose catabolism, its transamination product, alanine, is
      also produced in significant quantities. The oxidative branch of the pentose
      phosphate pathway is operative, although the non-oxidative branch is not. Ribose
      5-phosphate generated through this pathway distributes widely into nucleotide
      synthesis and other branches of metabolism. Acetate, derived from glucose, is
      found associated with a range of acetylated amino acids and, to a lesser extent,
      fatty acids; while labelled glycerol is found in many glycerophospholipids.
      Glucose also enters inositol and several sugar nucleotides that serve as
      precursors to macromolecule biosynthesis. Although a Krebs cycle is not
      operative, malate, fumarate and succinate, primarily labelled in three carbons,
      were present, indicating an origin from phosphoenolpyruvate via oxaloacetate.
      Interestingly, the enzyme responsible for conversion of phosphoenolpyruvate to
      oxaloacetate, phosphoenolpyruvate carboxykinase, was shown to be essential to the
      bloodstream form trypanosomes, as demonstrated by the lethal phenotype induced by
      RNAi-mediated downregulation of its expression. In addition, glucose derivatives
      enter pyrimidine biosynthesis via oxaloacetate as a precursor to aspartate and
      orotate. 

PMID- 25775472
TI  - Generic switching and non-persistence among medicine users: a combined population
      based questionnaire and register study.
AB  - BACKGROUND: Generic substitution means that one medicinal product is replaced by
      another product containing the same active substance. It is strictly regulated
      with respect to its bioequivalence, and all products must have undergone
      appropriate studies. Although generic substitution is widely implemented, it
      still remains to be answered how generic switch influences persistence to long
      term treatment, and if it is modified by patients' concerns about medicine and
      views on generic medicine. This study focuses on users of antidepressants and
      antiepileptics, and their experience of generic switching. METHODS: The study was
      an observational cohort study. By use of a prescription database, we identified
      patients who had redeemed prescriptions on generically substitutable drugs, and a
      questionnaire was mailed to them. We analyzed predictors of discontinuation in
      relation to generic switch and patients' attitudes towards generic medicines and
      concerns about their medicine. RESULTS: Patients who experience their first-time
      switch of a specific drug were at higher risk of non-persistence, Hazard Ratio
      2.98, 95% CI (1.81;4.89) versus those who have never switched, and 35.7% became
      non-persistent during the first year of follow-up. Generic switching did not
      influence persistence considerably in those having previous experience with
      generic switching of the specific drug. Stratified analyses on users of
      antidepressants and antiepileptics underpin the results, showing higher risk of
      non-persistence for first-time switchers for both drug categories. CONCLUSION: In
      conclusion, patients who are first-time switchers of a specific drug were at
      higher risk of non-persistence compared to never switchers and those having
      experienced previous generic switching.

PMID- 25775473
TI  - High female survival promotes evolution of protogyny and sexual conflict.
AB  - Existing models explaining the evolution of sexual dimorphism in the timing of
      emergence (SDT) in Lepidoptera assume equal mortality rates for males and
      females. The limiting assumption of equal mortality rates has the consequence
      that these models are only able to explain the evolution of emergence of males
      before females, i.e. protandry-the more common temporal sequence of emergence in
      Lepidoptera. The models fail, however, in providing adaptive explanations for the
      evolution of protogyny, where females emerge before males, but protogyny is not
      rare in insects. The assumption of equal mortality rates seems too restrictive
      for many insects, such as butterflies. To investigate the influence of unequal
      mortality rates on the evolution of SDT, we present a generalised version of a
      previously published model where we relax this assumption. We find that longer
      life-expectancy of females compared to males can indeed favour the evolution of
      protogyny as a fitness enhancing strategy. Moreover, the encounter rate between
      females and males and the sex-ratio are two important factors that also influence
      the evolution of optimal SDT. If considered independently for females and males
      the predicted strategies can be shown to be evolutionarily stable (ESS). Under
      the assumption of equal mortality rates the difference between the females' and
      males' ESS remains typically very small. However, female and male ESS may be
      quite dissimilar if mortality rates are different. This creates the potential for
      an 'evolutionary conflict' between females and males. Bagworm moths (Lepidoptera:
      Psychidae) provide an exemplary case where life-history attributes are such that
      protogyny should indeed be the optimal emergence strategy from the males' and
      females' perspectives: (i) Female longevity is considerably larger than that of
      males, (ii) encounter rates between females and males are presumably low, and
      (iii) females mate only once. Protogyny is indeed the general mating strategy
      found in the bagworm family. 

PMID- 25775474
TI  - Dietary triacylglycerols with palmitic acid in the sn-2 position modulate levels
      of N-acylethanolamides in rat tissues.
AB  - BACKGROUND: Several evidences suggest that the position of palmitic acid (PA) in
      dietary triacylglycerol (TAG) influences different biological functions. We aimed
      at evaluating whether dietary fat with highly enriched (87%) PA in sn-2 position
      (Hsn-2 PA), by increasing PA incorporation into tissue phospholipids (PL),
      modifies fatty acid profile and biosynthesis of fatty acid-derived bioactive
      lipids, such as endocannabinoids and their congeners. STUDY DESIGN: Rats were fed
      for 5 weeks diets containing Hsn-2 PA or fat with PA randomly distributed in TAG
      with 18.8% PA in sn-2 position (Lsn-2 PA), and similar total PA concentration.
      Fatty acid profile in different lipid fractions, endocannabinoids and congeners
      were measured in intestine, liver, visceral adipose tissue, muscle and brain.
      RESULTS: Rats on Hsn-2 PA diet had lower levels of anandamide with concomitant
      increase of its congener palmitoylethanolamide and its precursor PA into visceral
      adipose tissue phospholipids. In addition, we found an increase of
      oleoylethanolamide, an avid PPAR alpha ligand, in liver, muscle and brain,
      associated to higher levels of its precursor oleic acid in liver and muscle,
      probably derived by elongation and further delta 9 desaturation of PA. Changes in
      endocannabinoids and congeners were associated to a decrease of circulating TNF
      alpha after LPS challenge, and to an improved feed efficiency. CONCLUSIONS:
      Dietary Hsn-2 PA, by modifying endocannabinoids and congeners biosynthesis in
      different tissues may potentially concur in the physiological regulation of
      energy metabolism, brain function and body fat distribution.

PMID- 25775475
TI  - Immune activation response in chronic HIV-infected patients: influence of
      Hepatitis C virus coinfection.
AB  - OBJECTIVES: We have analyzed the parameters (bacterial translocation, immune
      activation and regulation, presence of HCV coinfection) which could be implicated
      in an inappropriate immune response from individuals with chronic HIV infection.
      The influence of them on the evolution of CD4+ T cell count has been
      investigated. PATIENTS AND METHODS: Seventy HIV-infected patients [monoinfected
      by HIV (n = 20), HCV-coinfected (with (n = 25) and without (n = 25) liver
      cirrhosis)] and 25 healthy controls were included. Median duration of HIV
      infection was 20 years. HIV- and HCV-related parameters, as well as markers
      relative to bacterial translocation, monocyte and lymphocyte activation and
      regulation were considered as independent variables. Dependent variables were the
      increase of CD4+ T cell count during the follow-up (12 months). RESULTS:
      Increased values of bacterial translocation, measured by lipopolysaccharide
      binding protein, monocyte and lymphocyte activation markers and T regulatory
      lymphocytes were detected in HIV-monoinfected and HIV/HCV coinfected patients.
      Serum sCD14 and IL-6 were increased in HIV/HCV-coinfected patients with liver
      cirrhosis in comparison with those with chronic hepatitis or HIV-monoinfected
      individuals. Time with undetectable HIV load was not related with these
      parameters. The presence of cirrhosis was negatively associated with a CD4+ T
      cell count increase. CONCLUSION: In patients with a chronic HIV infection, a
      persistent increase of lipopolysaccharide-binding protein and monocyte and
      lymphocyte modifications are present. HCV-related cirrhosis is associated with
      more elevated serum concentrations of monocyte-derived markers. Cirrhosis
      influences the continued immune reconstitution of these patients.

PMID- 25775476
TI  - Changes in individual weight status based on body mass index and waist
      circumference in Hong Kong Chinese.
AB  - BACKGROUND: Weight change predicted diseases and mortality. We investigate 3-year
      changes in individual body mass index (BMI) and waist circumference in Hong Kong
      Chinese adults. METHODS: In the Population Health Survey, 7084 adults in 2003
      (baseline) were followed up in 2006. Longitudinal anthropometric data were
      available in 2941 (41.5%) for BMI and 2956 for waist circumference. Weight status
      and central obesity were based on objectively measured BMI and waist
      circumference using Asian standards. RESULTS: Mean BMI (SD) increased from 22.8
      (3.62) to 23.1 (3.95) (p<0.001) with 1.3 percentage point increase in prevalence
      of overweight and obesity (from 44.3% to 45.6%). One in 5 (22.0%) normal or
      underweight baseline respondents became overweight or obese and a similar
      proportion (24.8%) of overweight and obese respondents became normal or
      underweight. Prevalence of central obesity increased from 28.3% to 32.4%
      (p<0.001) with a non-significantly greater increase in women (30.0% to 38.1%)
      than men (23.0% to 26.1%) (p=0.63). A higher proportion of centrally obese
      respondents returned to normal (29.4%) than normal respondents developing central
      obesity (17.4%). CONCLUSIONS: This is one of the few studies in Chinese, which
      found dynamic longitudinal changes (increase/stable/decrease) in individual
      weight status and waist circumference. Future studies with better follow-up and
      investigating the causes of such changes are warranted.

PMID- 25775477
TI  - Pregnancy-induced amelioration of muscular dystrophy phenotype in mdx mice via
      muscle membrane stabilization effect of glucocorticoid.
AB  - Duchenne muscular dystrophy (DMD), the most common and severe type of
      dystrophinopathy, is an X-linked recessive genetic disease caused by the absence
      of dystrophin, which leads to fragility and vulnerability of the sarcolemma to
      mechanical stretching with increased membrane permeability. Currently,
      glucocorticoids such as prednisolone are the only medication available for DMD.
      However, molecular pathways responsible for this effect are still unclear. In
      addition, it remains unclear whether sex-related factors, including pregnancy and
      the postpartum period, affect the phenotype of dystrophinopathy. Here, we report
      the amelioration of muscle membrane permeability in the diaphragm muscle of
      pregnant and postpartum, but not in nulliparous, mdx mice, an animal model for
      DMD, during the physiological surge of corticosterone, the most abundant
      glucocorticoid in rodents. Cultures of single muscle fibers and myotubes isolated
      from mdx mouse diaphragm demonstrate resistance to hypo-osmotic shock when
      treated with corticosterone but not with estradiol or progesterone. This
      corticosterone-mediated resistance was diminished by an antagonist of
      corticosterone, indicating that the glucocorticoid-glucocorticoid receptor axis
      plays a role in this membrane stabilization effect on muscle. Moreover,
      subcutaneous injection of corticosterone into mdx mice showed decreased membrane
      permeability. This is the first report to demonstrate that pregnancy-related
      resistance to muscle fiber damage in mdx mice due to the membrane stabilization
      effect of corticosterone. We also propose that this membrane stabilization effect
      is exerted through annexin A1 up-regulation as the molecular mechanisms of
      glucocorticoid effects on DMD muscle. Furthermore, single muscle fiber culture
      studies provide a sensitive chemical screening platform for muscular dystrophies.

PMID- 25775478
TI  - Can the red-green duochrome test be used prior to correcting the refractive
      cylinder component?
AB  - PURPOSE: A primary task of the eye care professional is determining the
      refraction, or optical correction, of a patient. The duochrome red-green test is
      a standard tool for verification of the final refraction. Traditionally, it is
      recommended for use both prior to and subsequent to determining the cylindrical
      or astigmatic component of the refraction. In order for it to be effective when
      used before correcting the cylinder it is necessary that the COLC (Circle of
      Least Confusion) be on the retina. This study examined whether it is necessarily
      true that the duochrome response in uncorrected astigmatism will be as trust
      worthy as it is with corrected cylinders. METHODS: The red-green examination was
      performed monocularly under the following three conditions: a. fully corrected
      refraction for the subgroup of eyes that had spherical refractions and for the
      subgroup of eyes with sphero-cylindrical refractions. b. best sphere-only
      correction without cylinder correction in sphero-cylindrical eyes c. an induced
      cylinder error in spherical eyes. The interval between the last "red" response
      and the first "green" response for the right eyes as a group and separately for
      the physiological cylinder and induced cylinder correction sub-groups was
      calculated and compared using a paired, two-tailed t-test. RESULTS: The intervals
      between "red" and "green" responses were not significantly different in the
      population as a whole and in the uncorrected physiological cylinder and induced
      cylinder subgroups examined. CONCLUSION: Based on the finding that the interval
      of red-green equality with fully corrected cylinder and without the cylindrical
      correction are not significantly different, the red-green duochrome test can
      indeed be used both before and after cylindrical correction.

PMID- 25775479
TI  - Identification of a biomarker in cerebrospinal fluid for neuronopathic forms of
      Gaucher disease.
AB  - Gaucher disease, a recessive inherited metabolic disorder caused by defects in
      the gene encoding glucosylceramidase (GlcCerase), can be divided into three
      subtypes according to the appearance of symptoms associated with central nervous
      system involvement. We now identify a protein, glycoprotein non-metastatic B
      (GPNMB), that acts as an authentic marker of brain pathology in neurological
      forms of Gaucher disease. Using three independent techniques, including
      quantitative global proteomic analysis of cerebrospinal fluid (CSF) in samples
      from Gaucher disease patients that display neurological symptoms, we demonstrate
      a correlation between the severity of symptoms and GPNMB levels. Moreover, GPNMB
      levels in the CSF correlate with disease severity in a mouse model of Gaucher
      disease. GPNMB was also elevated in brain samples from patients with type 2 and 3
      Gaucher disease. Our data suggest that GPNMB can be used as a marker to quantify
      neuropathology in Gaucher disease patients and as a marker of treatment efficacy
      once suitable treatments towards the neurological symptoms of Gaucher disease
      become available. 

PMID- 25775481
TI  - Correction: rapamycin ameliorates nephropathy despite elevating hyperglycemia in
      a polygenic mouse model of type 2 diabetes, NONcNZO10/LtJ.

PMID- 25775480
TI  - 3D algebraic iterative reconstruction for cone-beam x-ray differential phase
      contrast computed tomography.
AB  - Due to the potential of compact imaging systems with magnified spatial resolution
      and contrast, cone-beam x-ray differential phase-contrast computed tomography
      (DPC-CT) has attracted significant interest. The current proposed FDK
      reconstruction algorithm with the Hilbert imaginary filter will induce severe
      cone-beam artifacts when the cone-beam angle becomes large. In this paper, we
      propose an algebraic iterative reconstruction (AIR) method for cone-beam DPC-CT
      and report its experiment results. This approach considers the reconstruction
      process as the optimization of a discrete representation of the object function
      to satisfy a system of equations that describes the cone-beam DPC-CT imaging
      modality. Unlike the conventional iterative algorithms for absorption-based CT,
      it involves the derivative operation to the forward projections of the
      reconstructed intermediate image to take into account the differential nature of
      the DPC projections. This method is based on the algebraic reconstruction
      technique, reconstructs the image ray by ray, and is expected to provide better
      derivative estimates in iterations. This work comprises a numerical study of the
      algorithm and its experimental verification using a dataset measured with a three
      grating interferometer and a mini-focus x-ray tube source. It is shown that the
      proposed method can reduce the cone-beam artifacts and performs better than FDK
      under large cone-beam angles. This algorithm is of interest for future cone-beam
      DPC-CT applications. 

PMID- 25775482
TI  - Sex and Smoking Status Effects on the Early Detection of Early Lung Cancer in
      High-Risk Smokers Using an Electronic Nose.
AB  - OBJECTIVE: Volatile organic compounds (VOCs) in exhaled breath as measured by
      electronic nose (e-nose) have utility as biomarkers to detect subjects at risk of
      having lung cancer in a screening setting. We hypothesize that breath analysis
      using an e-nose chemo-resistive sensor array could be used as a screening tool to
      discriminate patients diagnosed with lung cancer from high-risk smokers. METHODS:
      Breath samples from 191 subjects-25 lung cancer patients and 166 high-risk smoker
      control subjects without cancer-were analyzed. For clinical relevancy, subjects
      in both groups were matched for age, sex, and smoking histories. Classification
      and regression trees and discriminant functions classifiers were used to
      recognize VOC patterns in e-nose data. Cross-validated results were used to
      assess classification accuracy. Repeatability and reproducibility of e-nose data
      were assessed by measuring subject-exhaled breath in parallel across two e-nose
      devices. RESULTS: e-Nose measurements could distinguish lung cancer patients from
      high-risk control subjects, with a better than 80% classification accuracy.
      Subject sex and smoking status impacted classification as area under the curve
      results (ex-smoker males 0.846, ex-smoker female 0.816, current smoker male
      0.745, and current smoker female 0.725) demonstrated. Two e-nose systems could be
      calibrated to give equivalent readings across subject-exhaled breath measured in
      parallel. CONCLUSIONS: e-Nose technology may have significant utility as a
      noninvasive screening tool for detecting individuals at increased risk for lung
      cancer. SIGNIFICANCE: The results presented further the case that VOC patterns
      could have real clinical utility to screen for lung cancer in the important
      growing ex-smoker population.

PMID- 25775483
TI  - A Novel Kalman Filter for Human Motion Tracking With an Inertial-Based Dynamic
      Inclinometer.
AB  - GOAL: Design and development of a linear Kalman filter to create an inertial
      based inclinometer targeted to dynamic conditions of motion. METHODS: The
      estimation of the body attitude (i.e., the inclination with respect to the
      vertical) was treated as a source separation problem to discriminate the gravity
      and the body acceleration from the specific force measured by a triaxial
      accelerometer. The sensor fusion between triaxial gyroscope and triaxial
      accelerometer data was performed using a linear Kalman filter. Wrist-worn
      inertial measurement unit data from ten participants were acquired while
      performing two dynamic tasks: 60-s sequence of seven manual activities and 90 s
      of walking at natural speed. Stereophotogrammetric data were used as a reference.
      A statistical analysis was performed to assess the significance of the accuracy
      improvement over state-of-the-art approaches. RESULTS: The proposed method
      achieved, on an average, a root mean square attitude error of 3.6 degrees  and
      1.8 degrees  in manual activities and locomotion tasks (respectively). The
      statistical analysis showed that, when compared to few competing methods, the
      proposed method improved the attitude estimation accuracy. CONCLUSION: A novel
      Kalman filter for inertial-based attitude estimation was presented in this study.
      A significant accuracy improvement was achieved over state-of-the-art approaches,
      due to a filter design that better matched the basic optimality assumptions of
      Kalman filtering. SIGNIFICANCE: Human motion tracking is the main application
      field of the proposed method. Accurately discriminating the two components
      present in the triaxial accelerometer signal is well suited for studying both the
      rotational and the linear body kinematics.

PMID- 25775484
TI  - Compressed Sensing of Multichannel EEG Signals: The Simultaneous Cosparsity and
      Low-Rank Optimization.
AB  - GOAL: This paper deals with the problems that some EEG signals have no good
      sparse representation and single-channel processing is not computationally
      efficient in compressed sensing of multichannel EEG signals. METHODS: An
      optimization model with L0 norm and Schatten-0 norm is proposed to enforce
      cosparsity and low-rank structures in the reconstructed multichannel EEG signals.
      Both convex relaxation and global consensus optimization with alternating
      direction method of multipliers are used to compute the optimization model.
      RESULTS: The performance of multichannel EEG signal reconstruction is improved in
      term of both accuracy and computational complexity. CONCLUSION: The proposed
      method is a better candidate than previous sparse signal recovery methods for
      compressed sensing of EEG signals. SIGNIFICANCE: The proposed method enables
      successful compressed sensing of EEG signals even when the signals have no good
      sparse representation. Using compressed sensing would much reduce the power
      consumption of wireless EEG system.

PMID- 25775485
TI  - Field Reliability Estimation for Cochlear Implants.
AB  - Cochlear implants are electronic devices used to provide useful hearing
      sensations to patients with severe to profound hearing loss. Safety and
      reliability are considered by patients and clinicians when selecting among the
      different models of cochlear implants. However, comparing reliability estimates
      from different manufacturers is difficult because of the lack of a standardized
      approach for classifying and quantifying failure data. This paper develops a
      classification scheme for cochlear implant failures wherein each failure report
      is categorized based on the failure site, cause, mode, and mechanism obtained
      through failure modes, mechanisms, and effects analysis. Failure parameters based
      on the Weibull distribution are used to quantify the following reliability
      metrics: B1, B5, B10, and B50 lives. The developed reporting scheme provides
      clear and quantitative information on failure causes and failure sites for a
      given implant. This method provides a consistent reporting format for
      communicating field reliability to regulatory units, clinicians, and patients. 

PMID- 25775487
TI  - Ultrasound guidance for beating heart mitral valve repair augmented by synthetic
      dynamic CT.
AB  - Minimally invasive valvular intervention commonly requires intra-procedural
      navigation to provide spatial and temporal information of relevant cardiac
      structures and device components. Recently intra-procedural trans-esophageal
      echocardiography (TEE) has been exploited for this purpose due to its
      accessibility, low cost, ease of use, and real-time imaging capacity. However,
      the position and orientation of tissue targets relative to surgical tools can be
      challenging to perceive, particularly using 2D imaging planes. In this paper, we
      propose the use of CT images to provide a high-quality 3D context to enhance
      ultrasound images through image registration, providing an augmented guidance
      system with minimal impact on standard clinical workflow. We also describe an
      approach to generate synthetic 4D CT images through non-rigid registration of
      available ultrasound. This can be employed to avoid a requirement for higher
      radiation. Synthetic CT images were validated through direct comparison of
      synthetic and real multi-phase CT images. Validation of CT and ultrasound image
      registration was performed for both dynamic and synthetic CT image datasets. Our
      results demonstrated that the synthetically generated dynamic CT images provide
      similar anatomical representation for relevant cardiac anatomy relative to real
      dynamic CT images, and similar high registration accuracy that can be achieved
      for intra-procedural TEE to this versus real dynamic CT images. 

PMID- 25775486
TI  - Higher-Order Motion-Compensation for In Vivo Cardiac Diffusion Tensor Imaging in
      Rats.
AB  - Motion of the heart has complicated in vivo applications of cardiac diffusion MRI
      and diffusion tensor imaging (DTI), especially in small animals such as rats
      where ultra-high-performance gradient sets are currently not available. Even with
      velocity compensation via, for example, bipolar encoding pulses, the variable
      shot-to-shot residual motion-induced spin phase can still give rise to pronounced
      artifacts. This study presents diffusion-encoding schemes that are designed to
      compensate for higher-order motion components, including acceleration and jerk,
      which also have the desirable practical features of minimal TEs and high
      achievable b-values. The effectiveness of these schemes was verified numerically
      on a realistic beating heart phantom, and demonstrated empirically with in vivo
      cardiac diffusion MRI in rats. Compensation for acceleration, and lower motion
      components, was found to be both necessary and sufficient for obtaining diffusion
      weighted images of acceptable quality and SNR, which yielded the first in vivo
      cardiac DTI demonstrated in the rat. These findings suggest that compensation for
      higher order motion, particularly acceleration, can be an effective alternative
      solution to high-performance gradient hardware for improving in vivo cardiac DTI.

PMID- 25775488
TI  - Scalable mobile image retrieval by exploring contextual saliency.
AB  - Nowadays, it is very convenient to capture photos by a smart phone. As using, the
      smart phone is a convenient way to share what users experienced anytime and
      anywhere through social networks, it is very possible that we capture multiple
      photos to make sure the content is well photographed. In this paper, an effective
      scalable mobile image retrieval approach is proposed by exploring contextual
      salient information for the input query image. Our goal is to explore the high
      level semantic information of an image by finding the contextual saliency from
      multiple relevant photos rather than solely using the input image. Thus, the
      proposed mobile image retrieval approach first determines the relevant photos
      according to visual similarity, then mines salient features by exploring
      contextual saliency from multiple relevant images, and finally determines
      contributions of salient features for scalable retrieval. Compared with the
      existing mobile-based image retrieval approaches, our approach requires less
      bandwidth and has better retrieval performance. We can carry out retrieval with
      <200-B data, which is <5% of existing approaches. Most importantly, when the
      bandwidth is limited, we can rank the transmitted features according to their
      contributions to retrieval. Experimental results show the effectiveness of the
      proposed approach. 

PMID- 25775489
TI  - Utilizing image scales towards totally training free blind image quality
      assessment.
AB  - A new approach to blind image quality assessment (BIQA), requiring no training,
      is proposed in this paper. The approach is named as blind image quality evaluator
      based on scales and works by evaluating the global difference of the query image
      analyzed at different scales with the query image at original resolution. The
      approach is based on the ability of the natural images to exhibit redundant
      information over various scales. A distorted image is considered as a deviation
      from the natural image and bereft of the redundancy present in the original
      image. The similarity of the original resolution image with its down-scaled
      version will decrease more when the image is distorted more. Therefore, the
      dissimilarities of an image with its low-resolution versions are cumulated in the
      proposed method. We dissolve the query image into its scale-space and measure the
      global dissimilarity with the co-occurrence histograms of the original and its
      scaled images. These scaled images are the low pass versions of the original
      image. The dissimilarity, called low pass error, is calculated by comparing the
      low pass versions across scales with the original image. The high pass versions
      of the image in different scales are obtained by Wavelet decomposition and their
      dissimilarity from the original image is also calculated. This dissimilarity,
      called high pass error, is computed with the variance and gradient histograms and
      weighted by the contrast sensitivity function to make it perceptually effective.
      These two kinds of dissimilarities are combined together to derive the quality
      score of the query image. This method requires absolutely no training with the
      distorted image, pristine images, or subjective human scores to predict the
      perceptual quality but uses the intrinsic global change of the query image across
      scales. The performance of the proposed method is evaluated across six publicly
      available databases and found to be competitive with the state-of-the-art
      techniques. 

PMID- 25775490
TI  - Exemplar-based inpainting: technical review and new heuristics for better
      geometric reconstructions.
AB  - This paper proposes a technical review of exemplar-based inpainting approaches
      with a particular focus on greedy methods. Several comparative and illustrative
      experiments are provided to deeply explore and enlighten these methods, and to
      have a better understanding on the state-of-the-art improvements of these
      approaches. From this analysis, three improvements over Criminisi et al.
      algorithm are then presented and detailed: 1) a tensor-based data term for a
      better selection of pixel candidates to fill in; 2) a fast patch lookup strategy
      to ensure a better global coherence of the reconstruction; and 3) a novel fast
      anisotropic spatial blending algorithm that reduces typical block artifacts using
      tensor models. Relevant comparisons with the state-of-the-art inpainting methods
      are provided that exhibit the effectiveness of our contributions. 

PMID- 25775491
TI  - Joint source-channel rate allocation and client clustering for scalable
      multistream IPTV.
AB  - We design a system framework for streaming scalable internet protocol television
      (IPTV) content to heterogenous clients. The backbone bandwidth is optimally
      allocated between source and parity data layers that are delivered to the client
      population. The assignment of stream layers to clients is done based on their
      access link data rate and packet loss characteristics, and is part of the
      optimization. We design three techniques for jointly computing the optimal number
      of multicast sessions, their respective source and parity rates, and client
      membership, either exactly or approximatively, at lower complexity. The latter is
      achieved via an iterative coordinate descent algorithm that only marginally
      underperforms relative to the exact analytic solution. Through experiments, we
      study the advantages of our framework over common IPTV systems that deliver the
      same source and parity streams to every client. We observe substantial gains in
      video quality in terms of both its average value and standard deviation over the
      client population. In addition, for energy efficiency, we propose to move the
      parity data generation part to the edge of the backbone network, where each
      client connects to its IPTV stream. We analytically study the conditions under
      which such an approach delivers energy savings relative to the conventional case
      of source and parity data generation at the IPTV streaming server. Finally, we
      demonstrate that our system enables more consistent streaming performance, when
      the clients' access link packet loss distribution is varied, relative to the two
      baseline methods used in our investigation, and maintains the same performance as
      an ideal system that serves each client independently. 

PMID- 25775492
TI  - Motion-compensated coding and frame rate up-conversion: models and analysis.
AB  - Block-based motion estimation (ME) and motion compensation (MC) techniques are
      widely used in modern video processing algorithms and compression systems. The
      great variety of video applications and devices results in diverse compression
      specifications, such as frame rates and bit rates. In this paper, we study the
      effect of frame rate and compression bit rate on block-based ME and MC as
      commonly utilized in inter-frame coding and frame rate up-conversion (FRUC). This
      joint examination yields a theoretical foundation for comparing MC procedures in
      coding and FRUC. First, the video signal is locally modeled as a noisy
      translational motion of an image. Then, we theoretically model the motion
      compensated prediction of available and absent frames as in coding and FRUC
      applications, respectively. The theoretic MC-prediction error is studied further
      and its autocorrelation function is calculated, yielding useful separable
      simplifications for the coding application. We argue that a linear relation
      exists between the variance of the MC-prediction error and temporal distance.
      While the relevant distance in MC coding is between the predicted and reference
      frames, MC-FRUC is affected by the distance between the frames available for
      interpolation. We compare our estimates with experimental results and show that
      the theory explains qualitatively the empirical behavior. Then, we use the models
      proposed to analyze a system for improving of video coding at low bit rates,
      using a spatio-temporal scaling. Although this concept is practically employed in
      various forms, so far it lacked a theoretical justification. We here harness the
      proposed MC models and present a comprehensive analysis of the system, to
      qualitatively predict the experimental results. 

PMID- 25775493
TI  - Face recognition across non-uniform motion blur, illumination, and pose.
AB  - Existing methods for performing face recognition in the presence of blur are
      based on the convolution model and cannot handle non-uniform blurring situations
      that frequently arise from tilts and rotations in hand-held cameras. In this
      paper, we propose a methodology for face recognition in the presence of space
      varying motion blur comprising of arbitrarily-shaped kernels. We model the
      blurred face as a convex combination of geometrically transformed instances of
      the focused gallery face, and show that the set of all images obtained by non
      uniformly blurring a given image forms a convex set. We first propose a non
      uniform blur-robust algorithm by making use of the assumption of a sparse camera
      trajectory in the camera motion space to build an energy function with l1 -norm
      constraint on the camera motion. The framework is then extended to handle
      illumination variations by exploiting the fact that the set of all images
      obtained from a face image by non-uniform blurring and changing the illumination
      forms a bi-convex set. Finally, we propose an elegant extension to also account
      for variations in pose. 

PMID- 25775494
TI  - Tele-Supervised FES-Assisted Exercise for Hemiplegic Upper Limb.
AB  - Stroke survivors often have upper limb (UL) hemiparesis, limiting their ability
      to perform activities of daily life (ADLs). Intensive, task-oriented exercise
      therapy (ET) can improve UL function, but motivation to perform sufficient ET is
      difficult to maintain. Here, we report on a trial in which a workstation was
      deployed in the homes of chronic stroke survivors to enable tele-coaching of ET
      in the guise of computer games. Participants performed six weeks of 1 h/day, five
      days/week ET. Hand opening and grasp were assisted with functional electrical
      stimulation (FES). The primary outcome measure was the Action Research Arm Test
      (ARAT). Secondary outcome measures included a quantitative test of UL function
      performed on the workstation, grasp force measurements and transcranial magnetic
      stimulation (TMS). Improvements were seen in the functional tests, but
      surprisingly, not in the TMS responses. An important finding was that
      participants commencing with intermediate functional scores improved the most.
      CONCLUSIONS: (1) Daily, tele-supervised FES-ET in chronic stroke survivors is
      feasible with commercially-available technology. (2) The intervention can
      significantly improve UL function, particularly in people who start with an
      intermediate level of function. (3) Significant improvements in UL function can
      occur in the absence of changes in TMS responses.

PMID- 25775495
TI  - Language-Model Assisted Brain Computer Interface for Typing: A Comparison of
      Matrix and Rapid Serial Visual Presentation.
AB  - Noninvasive electroencephalography (EEG)-based brain-computer interfaces (BCIs)
      popularly utilize event-related potential (ERP) for intent detection.
      Specifically, for EEG-based BCI typing systems, different symbol presentation
      paradigms have been utilized to induce ERPs. In this manuscript, through an
      experimental study, we assess the speed, recorded signal quality, and system
      accuracy of a language-model-assisted BCI typing system using three different
      presentation paradigms: a 4 * 7 matrix paradigm of a 28-character alphabet with
      row-column presentation (RCP) and single-character presentation (SCP), and rapid
      serial visual presentation (RSVP) of the same. Our analyses show that signal
      quality and classification accuracy are comparable between the two visual
      stimulus presentation paradigms. In addition, we observe that while the matrix
      based paradigm can be generally employed with lower inter-trial-interval (ITI)
      values, the best presentation paradigm and ITI value configuration is user
      dependent. This potentially warrants offering both presentation paradigms and
      variable ITI options to users of BCI typing systems. 

PMID- 25775497
TI  - Dual-Phase Tapped-Delay-Line Time-to-Digital Converter With On-the-Fly
      Calibration Implemented in 40 nm FPGA.
AB  - This paper describes two novel time-to-digital converter (TDC) architectures. The
      first is a dual-phase tapped-delay-line (TDL) TDC architecture that allows us to
      minimize the clock skew problem that causes the highly nonlinear characteristics
      of the TDC. The second is a pipelined on-the-fly calibration architecture that
      continuously compensates the nonlinearity and calibrates the fine times using the
      most up-to-date bin widths without additional dead time. The two architectures
      were combined and implemented in a single Virtex-6 device (ML605, Xilinx) for
      time interval measurement. The standard uncertainty for the time intervals from 0
      to 20 ns was less than 12.83 ps-RMS (root mean square). The resolution (i.e., the
      least significant bit, LSB) of the TDC was approximately 10 ps at room
      temperature. The differential nonlinearity (DNL) values were [-1.0, 1.91] and [
      1.0, 1.88] LSB and the integral nonlinearity (INL) values were [-2.20, 2.60] and
      [-1.63, 3.93] LSB for the two different TDLs that constitute one TDC channel.
      During temperature drift from 10 to 50( degrees )C, the TDC with on-the-fly
      calibration maintained the standard uncertainty of 11.03 ps-RMS. 

PMID- 25775496
TI  - A Novel Framework Based on FastICA for High Density Surface EMG Decomposition.
AB  - This study presents a progressive FastICA peel-off (PFP) framework for high
      density surface electromyogram (EMG) decomposition. The novel framework is based
      on a shift-invariant model for describing surface EMG. The decomposition process
      can be viewed as progressively expanding the set of motor unit spike trains,
      which is primarily based on FastICA. To overcome the local convergence of
      FastICA, a peel-off strategy, i.e., removal of the estimated motor unit action
      potential trains from the previous step, is used to mitigate the effects of the
      already identified motor units, so more motor units can be extracted. A
      constrained FastICA is applied to assess the extracted spike trains and correct
      possible erroneous or missed spikes. These procedures work together to improve
      decomposition performance. The proposed framework was validated using simulated
      surface EMG signals with different motor unit numbers (30, 70, 91) and SNRs (20,
      10, and 0 dB). The results demonstrated relatively large numbers of extracted
      motor units and high accuracies (high F1-scores). The framework was tested with
      111 trials of 64-channel electrode array experimental surface EMG signals during
      the first dorsal interosseous muscle contraction at different intensities. On
      average 14.1 +/-5.0 motor units were identified from each trial of experimental
      surface EMG signals. 

PMID- 25775498
TI  - An Imageless Ultrasound Device to Measure Local and Regional Arterial Stiffness.
AB  - Arterial stiffness (AS) has been shown to be an important marker for risk
      assessment of cardiovascular events. Local arterial stiffness (LAS) is
      conventionally measured by evaluating arterial distensibility at particular
      arterial sites through ultrasound imaging systems. Regional arterial stiffness
      (RAS) is generally obtained by evaluating carotid to femoral pulse wave velocity
      (cfPWV) through tonometric devices. RAS has a better prognostic value than LAS
      and cfPWV is considered as the gold standard of AS. Over the past few years our
      group has been developing ARTerial Stiffness Evaluation for Non-Invasive
      Screening (ARTSENS), an inexpensive and portable device to measure the LAS. It
      uses a single element ultrasound transducer to obtain A-Mode frames from the
      desired artery and is fully automated to enable a non-expert to perform
      measurements. In this work, we report an extension of ARTSENS to enable
      measurement of cfPWV that now makes it the only fully automatic device that can
      measure both LAS and RAS. In this paper, we provide a general review of the
      ARTSENS and compare it with other state-of-the-art AS measurement systems. cfPWV
      measurement using ARTSENS was cross-validated against SphygmoCor by successive
      measurements with both devices on 41 human subjects and excellent agreement
      between both devices was demonstrated (Coefficient of determination and, limits
      of agreement m/s). The inter-device correlation between ARTSENS and SphygmoCor
      was found to be better than other similar studies reported in the literature. 

PMID- 25775499
TI  - Localized Tactile Feedback on a Transparent Surface through Time-Reversal Wave
      Focusing.
AB  - This article addresses the problem of producing independent tactile stimuli to
      multiple fingers exploring a transparent solid surface without the need to track
      their positions. To this end, wave time-reversal was applied to re-focus
      displacement impulses in time and in space at one or several locations in a thin
      glass plate. This result was achieved using ultrasonic bending waves produced by
      a set of lamellar piezoelectric actuators bonded at the periphery of the plate.
      Starting from first principles, the relations linking implementation parameters
      to the performance of the display are developed. The mechanical design of the
      display, signal processing, and driving electronics are described. A set of
      engineering tradeoffs are made explicit and used for the design of a mock up
      device comprising a glass plate 148 * 210 * 0.5 mm (3). Tests indicate that a
      peak amplitude of 7 &#956m confined to a 20 mm (2) region could be obtained for
      an average power consumption of 45 mW. Simultaneous focusing at several locations
      was successfully achieved. We showed that a lumped-mass model for the fingertip
      can effectively describe the effect of an actual fingertip load at the focus
      point. Lastly, we elucidated a likely stimulation mechanism that involves the
      transient decoupling of the finger skin from the plate surface. This phenomenon
      explains the observed tactile effect. 

PMID- 25775500
TI  - A Divide-and-Conquer Method for Scalable Robust Multitask Learning.
AB  - Multitask learning (MTL) aims at improving the generalization performance of
      multiple tasks by exploiting the shared factors among them. An important line of
      research in the MTL is the robust MTL (RMTL) methods, which use trace-norm
      regularization to capture task relatedness via a low-rank structure. The existing
      algorithms for the RMTL optimization problems rely on the accelerated proximal
      gradient (APG) scheme that needs repeated full singular value decomposition (SVD)
      operations. However, the time complexity of a full SVD is O(min(md(2),m(2)d)) for
      an RMTL problem with m tasks and d features, which becomes unaffordable in real
      world MTL applications that often have a large number of tasks and high
      dimensional features. In this paper, we propose a scalable solution for large
      scale RMTL, with either the least squares loss or the squared hinge loss, by a
      divide-and-conquer method. The proposed method divides the original RMTL problem
      into several size-reduced subproblems, solves these cheaper subproblems in
      parallel by any base algorithm (e.g., APG) for RMTL, and then combines the
      results to obtain the final solution. Our theoretical analysis indicates that,
      with high probability, the recovery errors of the proposed divide-and-conquer
      algorithm are bounded by those of the base algorithm. Furthermore, in order to
      solve the subproblems with the least squares loss or the squared hinge loss, we
      propose two efficient base algorithms based on the linearized alternating
      direction method, respectively. Experimental results demonstrate that, with
      little loss of accuracy, our method is substantially faster than the state-of-the
      art APG algorithms for RMTL. 

PMID- 25775501
TI  - Facial Position and Expression-Based Human-Computer Interface for Persons With
      Tetraplegia.
AB  - A human-computer interface (namely Facial position and expression Mouse system,
      FM) for the persons with tetraplegia based on a monocular infrared depth camera
      is presented in this paper. The nose position along with the mouth status
      (close/open) is detected by the proposed algorithm to control and navigate the
      cursor as computer user input. The algorithm is based on an improved Randomized
      Decision Tree, which is capable of detecting the facial information efficiently
      and accurately. A more comfortable user experience is achieved by mapping the
      nose motion to the cursor motion via a nonlinear function. The infrared depth
      camera enables the system to be independent of illumination and color changes
      both from the background and on human face, which is a critical advantage over
      RGB camera-based options. Extensive experimental results show that the proposed
      system outperforms existing assistive technologies in terms of quantitative and
      qualitative assessments.

PMID- 25775502
TI  - Self-Adaptive Differential Evolution Algorithm With Zoning Evolution of Control
      Parameters and Adaptive Mutation Strategies.
AB  - The performance of the differential evolution (DE) algorithm is significantly
      affected by the choice of mutation strategies and control parameters. Maintaining
      the search capability of various control parameter combinations throughout the
      entire evolution process is also a key issue. A self-adaptive DE algorithm with
      zoning evolution of control parameters and adaptive mutation strategies is
      proposed in this paper. In the proposed algorithm, the mutation strategies are
      automatically adjusted with population evolution, and the control parameters
      evolve in their own zoning to self-adapt and discover near optimal values
      autonomously. The proposed algorithm is compared with five state-of-the-art DE
      algorithm variants according to a set of benchmark test functions. Furthermore,
      seven nonparametric statistical tests are implemented to analyze the experimental
      results. The results indicate that the overall performance of the proposed
      algorithm is better than those of the five existing improved algorithms. 

PMID- 25775503
TI  - The Analysis of Image Contrast: From Quality Assessment to Automatic Enhancement.
AB  - Proper contrast change can improve the perceptual quality of most images, but it
      has largely been overlooked in the current research of image quality assessment
      (IQA). To fill this void, we in this paper first report a new large dedicated
      contrast-changed image database (CCID2014), which includes 655 images and
      associated subjective ratings recorded from 22 inexperienced observers. We then
      present a novel reduced-reference image quality metric for contrast change
      (RIQMC) using phase congruency and statistics information of the image histogram.
      Validation of the proposed model is conducted on contrast related CCID2014,
      TID2008, CSIQ and TID2013 databases, and results justify the superiority and
      efficiency of RIQMC over a majority of classical and state-of-the-art IQA
      methods. Furthermore, we combine aforesaid subjective and objective assessments
      to derive the RIQMC based Optimal HIstogram Mapping (ROHIM) for automatic
      contrast enhancement, which is shown to outperform recently developed enhancement
      technologies. 

PMID- 25775504
TI  - A Local Structural Descriptor for Image Matching via Normalized Graph Laplacian
      Embedding.
AB  - This paper investigates graph spectral approaches to the problem of point pattern
      matching. Specifically, we concentrate on the issue of how to effectively use
      graph spectral properties to characterize point patterns in the presence of
      positional jitter and outliers. A novel local spectral descriptor is proposed to
      represent the attribute domain of feature points. For a point in a given point
      set, weight graphs are constructed on its neighboring points and then their
      normalized Laplacian matrices are computed. According to the known spectral
      radius of the normalized Laplacian matrix, the distribution of the eigenvalues of
      these normalized Laplacian matrices is summarized as a histogram to form a
      descriptor. The proposed spectral descriptor is finally combined with the
      approximate distance order for recovering correspondences between point-sets.
      Extensive experiments demonstrate the effectiveness of the proposed approach and
      its superiority to the existing methods. 

PMID- 25775505
TI  - Bisphenol S and F: A Systematic Review and Comparison of the Hormonal Activity of
      Bisphenol A Substitutes.
AB  - BACKGROUND: Increasing concern over bisphenol A (BPA) as an endocrine-disrupting
      chemical and its possible effects on human health have prompted the removal of
      BPA from consumer products, often labeled "BPA-free." Some of the chemical
      replacements, however, are also bisphenols and may have similar physiological
      effects in organisms. Bisphenol S (BPS) and bisphenol F (BPF) are two such BPA
      substitutes. OBJECTIVES: This review was carried out to evaluate the
      physiological effects and endocrine activities of the BPA substitutes BPS and
      BPF. Further, we compared the hormonal potency of BPS and BPF to that of BPA.
      METHODS: We conducted a systematic review based on the Office of Health
      Assessment and Translation (OHAT) protocol. RESULTS: We identified the body of
      literature to date, consisting of 32 studies (25 in vitro only, and 7 in vivo).
      The majority of these studies examined the hormonal activities of BPS and BPF and
      found their potency to be in the same order of magnitude and of similar action as
      BPA (estrogenic, antiestrogenic, androgenic, and antiandrogenic) in vitro and in
      vivo. BPS also has potencies similar to that of estradiol in membrane-mediated
      pathways, which are important for cellular actions such as proliferation,
      differentiation, and death. BPS and BPF also showed other effects in vitro and in
      vivo, such as altered organ weights, reproductive end points, and enzyme
      expression. CONCLUSIONS: Based on the current literature, BPS and BPF are as
      hormonally active as BPA, and they have endocrine-disrupting effects. CITATION:
      Rochester JR, Bolden AL. 2015. Bisphenol S and F: a systematic review and
      comparison of the hormonal activity of bisphenol A substitutes.

PMID- 25775506
TI  - A mobile phone food record app to digitally capture dietary intake for
      adolescents in a free-living environment: usability study.
AB  - BACKGROUND: Mobile technologies are emerging as valuable tools to collect and
      assess dietary intake. Adolescents readily accept and adopt new technologies;
      thus, a food record app (FRapp) may be a useful tool to better understand
      adolescents' dietary intake and eating patterns. OBJECTIVE: We sought to
      determine the amenability of adolescents, in a free-living environment with
      minimal parental input, to use the FRapp to record their dietary intake. METHODS:
      Eighteen community-dwelling adolescents (11-14 years) received detailed
      instructions to record their dietary intake for 3-7 days using the FRapp.
      Participants were instructed to capture before and after images of all foods and
      beverages consumed and to include a fiducial marker in the image. Participants
      were also asked to provide text descriptors including amount and type of all
      foods and beverages consumed. RESULTS: Eight of 18 participants were able to
      follow all instructions: included pre- and post-meal images, a fiducial marker,
      and a text descriptor and collected diet records on 2 weekdays and 1 weekend day.
      Dietary intake was recorded on average for 3.2 (SD 1.3 days; 68% weekdays and 32%
      weekend days) with an average of 2.2 (SD 1.1) eating events per day per
      participant. A total of 143 eating events were recorded, of which 109 had at
      least one associated image and 34 were recorded with text only. Of the 109 eating
      events with images, 66 included all foods, beverages and a fiducial marker and 44
      included both a pre- and post-meal image. Text was included with 78 of the
      captured images. Of the meals recorded, 36, 33, 35, and 39 were breakfasts,
      lunches, dinners, and snacks, respectively. CONCLUSIONS: These data suggest that
      mobile devices equipped with an app to record dietary intake will be used by
      adolescents in a free-living environment; however, a minority of participants
      followed all directions. User-friendly mobile food record apps may increase
      participant amenability, increasing our understanding of adolescent dietary
      intake and eating patterns. To improve data collection, the FRapp should deliver
      prompts for tasks, such as capturing images before and after each eating event,
      including the fiducial marker in the image, providing complete and accurate text
      information, and ensuring all eating events are recorded and should be
      customizable to individuals and to different situations. TRIAL REGISTRATION:
      Clinicaltrials.gov NCT01803997. http://clinicaltrials.gov/ct2/show/NCT01803997
      (Archived at: http://www.webcitation.org/6WiV1vxoR).

PMID- 25775507
TI  - The nucleolar ubiquitin-specific protease USP36 deubiquitinates and stabilizes c
      Myc.
AB  - c-Myc protein stability and activity are tightly regulated by the ubiquitin
      proteasome system. Aberrant stabilization of c-Myc contributes to many human
      cancers. c-Myc is ubiquitinated by SCF(Fbw7) (a SKP1-cullin-1-F-box complex that
      contains the F-box and WD repeat domain-containing 7, Fbw7, as the F-box protein)
      and several other ubiquitin ligases, whereas it is deubiquitinated and stabilized
      by ubiquitin-specific protease (USP) 28. The bulk of c-Myc degradation appears to
      occur in the nucleolus. However, whether c-Myc is regulated by deubiquitination
      in the nucleolus is not known. Here, we report that the nucleolar
      deubiquitinating enzyme USP36 is a novel c-Myc deubiquitinase. USP36 interacts
      with and deubiquitinates c-Myc in cells and in vitro, leading to the
      stabilization of c-Myc. This USP36 regulation of c-Myc occurs in the nucleolus.
      Interestingly, USP36 interacts with the nucleolar Fbw7gamma but not the
      nucleoplasmic Fbw7alpha. However, it abolished c-Myc degradation mediated both by
      Fbw7gamma and by Fbw7alpha. Consistently, knockdown of USP36 reduces the levels
      of c-Myc and suppresses cell proliferation. We further show that USP36 itself is
      a c-Myc target gene, suggesting that USP36 and c-Myc form a positive feedback
      regulatory loop. High expression levels of USP36 are found in a subset of human
      breast and lung cancers. Altogether, these results identified USP36 as a crucial
      and bono fide deubiquitinating enzyme controlling c-Myc's nucleolar degradation
      pathway. 

PMID- 25775508
TI  - PAB is an assembly chaperone that functions downstream of chaperonin 60 in the
      assembly of chloroplast ATP synthase coupling factor 1.
AB  - The chloroplast ATP synthase, a multisubunit complex in the thylakoid membrane,
      catalyzes the light-driven synthesis of ATP, thereby supplying the energy for
      carbon fixation during photosynthesis. The chloroplast ATP synthase is composed
      of both nucleus- and chloroplast-encoded proteins that have required the
      evolution of novel mechanisms to coordinate the biosynthesis and assembly of
      chloroplast ATP synthase subunits temporally and spatially. Here we have
      elucidated the assembly mechanism of the alpha3beta3gamma core complex of the
      chloroplast ATP synthase by identification and functional characterization of a
      key assembly factor, PAB (protein in chloroplast atpase biogenesis). PAB directly
      interacts with the nucleus-encoded gamma subunit and functions downstream of
      chaperonin 60 (Cpn60)-mediated CF1gamma subunit folding to promote its assembly
      into the catalytic core. PAB does not have any recognizable motifs or domains but
      is conserved in photosynthetic eukaryotes. It is likely that PAB evolved together
      with the transfer of chloroplast genes into the nucleus to assist nucleus-encoded
      CF1gamma assembly into the CF1 core. Such coordination might represent an
      evolutionarily conserved mechanism for folding and assembly of nucleus-encoded
      proteins to ensure proper assembly of multiprotein photosynthetic complexes.

PMID- 25775509
TI  - Endocytic proteins drive vesicle growth via instability in high membrane tension
      environment.
AB  - Clathrin-mediated endocytosis (CME) is a key pathway for transporting cargo into
      cells via membrane vesicles; it plays an integral role in nutrient import, signal
      transduction, neurotransmission, and cellular entry of pathogens and drug
      carrying nanoparticles. Because CME entails substantial local remodeling of the
      plasma membrane, the presence of membrane tension offers resistance to bending
      and hence, vesicle formation. Experiments show that in such high-tension
      conditions, actin dynamics is required to carry out CME successfully. In this
      study, we build on these pioneering experimental studies to provide fundamental
      mechanistic insights into the roles of two key endocytic proteins-namely, actin
      and BAR proteins-in driving vesicle formation in high membrane tension
      environment. Our study reveals an actin force-induced "snap-through instability"
      that triggers a rapid shape transition from a shallow invagination to a highly
      invaginated tubular structure. We show that the association of BAR proteins
      stabilizes vesicles and induces a milder instability. In addition, we present a
      rather counterintuitive role of BAR depolymerization in regulating the shape
      evolution of vesicles. We show that the dissociation of BAR proteins, supported
      by actin-BAR synergy, leads to considerable elongation and squeezing of vesicles.
      Going beyond the membrane geometry, we put forth a stress-based perspective for
      the onset of vesicle scission and predict the shapes and composition of detached
      vesicles. We present the snap-through transition and the high in-plane stress as
      possible explanations for the intriguing direct transformation of broad and
      shallow invaginations into detached vesicles in BAR mutant yeast cells. 

PMID- 25775510
TI  - MiR-2 family regulates insect metamorphosis by controlling the juvenile hormone
      signaling pathway.
AB  - In 2009 we reported that depletion of Dicer-1, the enzyme that catalyzes the
      final step of miRNA biosynthesis, prevents metamorphosis in Blattella germanica.
      However, the precise regulatory roles of miRNAs in the process have remained
      elusive. In the present work, we have observed that Dicer-1 depletion results in
      an increase of mRNA levels of Kruppel homolog 1 (Kr-h1), a juvenile hormone
      dependent transcription factor that represses metamorphosis, and that depletion
      of Kr-h1 expression in Dicer-1 knockdown individuals rescues metamorphosis. We
      have also found that the 3'UTR of Kr-h1 mRNA contains a functional binding site
      for miR-2 family miRNAs (for miR-2, miR-13a, and miR-13b). These data suggest
      that metamorphosis impairment caused by Dicer-1 and miRNA depletion is due to a
      deregulation of Kr-h1 expression and that this deregulation is derived from a
      deficiency of miR-2 miRNAs. We corroborated this by treating the last nymphal
      instar of B. germanica with an miR-2 inhibitor, which impaired metamorphosis, and
      by treating Dicer-1-depleted individuals with an miR-2 mimic to allow nymphal-to
      adult metamorphosis to proceed. Taken together, the data indicate that miR-2
      miRNAs scavenge Kr-h1 transcripts when the transition from nymph to adult should
      be taking place, thus crucially contributing to the correct culmination of
      metamorphosis. 

PMID- 25775511
TI  - A TOCA/CDC-42/PAR/WAVE functional module required for retrograde endocytic
      recycling.
AB  - Endosome-to-Golgi transport is required for the function of many key membrane
      proteins and lipids, including signaling receptors, small-molecule transporters,
      and adhesion proteins. The retromer complex is well-known for its role in cargo
      sorting and vesicle budding from early endosomes, in most cases leading to cargo
      fusion with the trans-Golgi network (TGN). Transport from recycling endosomes to
      the TGN has also been reported, but much less is understood about the molecules
      that mediate this transport step. Here we provide evidence that the F-BAR domain
      proteins TOCA-1 and TOCA-2 (Transducer of Cdc42 dependent actin assembly), the
      small GTPase CDC-42 (Cell division control protein 42), associated polarity
      proteins PAR-6 (Partitioning defective 6) and PKC-3/atypical protein kinase C,
      and the WAVE actin nucleation complex mediate the transport of MIG-14/Wls and TGN
      38/TGN38 cargo proteins from the recycling endosome to the TGN in Caenorhabditis
      elegans. Our results indicate that CDC-42, the TOCA proteins, and the WAVE
      component WVE-1 are enriched on RME-1-positive recycling endosomes in the
      intestine, unlike retromer components that act on early endosomes. Furthermore,
      we find that retrograde cargo TGN-38 is trapped in early endosomes after
      depletion of SNX-3 (a retromer component) but is mainly trapped in recycling
      endosomes after depletion of CDC-42, indicating that the CDC-42-associated
      complex functions after retromer in a distinct organelle. Thus, we identify a
      group of interacting proteins that mediate retrograde recycling, and link these
      proteins to a poorly understood trafficking step, recycling endosome-to-Golgi
      transport. We also provide evidence for the physiological importance of this
      pathway in WNT signaling. 

PMID- 25775512
TI  - Glucocorticoid-resistant Th17 cells are selectively attenuated by cyclosporine A.
AB  - Glucocorticoids remain the cornerstone of treatment for inflammatory conditions,
      but their utility is limited by a plethora of side effects. One of the key goals
      of immunotherapy across medical disciplines is to minimize patients'
      glucocorticoid use. Increasing evidence suggests that variations in the adaptive
      immune response play a critical role in defining the dose of glucocorticoids
      required to control an individual's disease, and Th17 cells are strong candidate
      drivers for nonresponsiveness [also called steroid resistance (SR)]. Here we use
      gene-expression profiling to further characterize the SR phenotype in T cells and
      show that Th17 cells generated from both SR and steroid-sensitive individuals
      exhibit restricted genome-wide responses to glucocorticoids in vitro, and that
      this is independent of glucocorticoid receptor translocation or isoform
      expression. In addition, we demonstrate, both in transgenic murine T cells in
      vitro and in an in vivo murine model of autoimmunity, that Th17 cells are
      reciprocally sensitive to suppression with the calcineurin inhibitor,
      cyclosporine A. This result was replicated in human Th17 cells in vitro, which
      were found to have a conversely large genome-wide shift in response to
      cyclosporine A. These observations suggest that the clinical efficacy of
      cyclosporine A in the treatment of SR diseases may be because of its selective
      attenuation of Th17 cells, and also that novel therapeutics, which target either
      Th17 cells themselves or the effector memory T-helper cell population from which
      they are derived, would be strong candidates for drug development in the context
      of SR inflammation. 

PMID- 25775513
TI  - Plant-derived antifungal agent poacic acid targets beta-1,3-glucan.
AB  - A rise in resistance to current antifungals necessitates strategies to identify
      alternative sources of effective fungicides. We report the discovery of poacic
      acid, a potent antifungal compound found in lignocellulosic hydrolysates of
      grasses. Chemical genomics using Saccharomyces cerevisiae showed that loss of
      cell wall synthesis and maintenance genes conferred increased sensitivity to
      poacic acid. Morphological analysis revealed that cells treated with poacic acid
      behaved similarly to cells treated with other cell wall-targeting drugs and
      mutants with deletions in genes involved in processes related to cell wall
      biogenesis. Poacic acid causes rapid cell lysis and is synergistic with
      caspofungin and fluconazole. The cellular target was identified; poacic acid
      localized to the cell wall and inhibited beta-1,3-glucan synthesis in vivo and in
      vitro, apparently by directly binding beta-1,3-glucan. Through its activity on
      the glucan layer, poacic acid inhibits growth of the fungi Sclerotinia
      sclerotiorum and Alternaria solani as well as the oomycete Phytophthora sojae. A
      single application of poacic acid to leaves infected with the broad-range fungal
      pathogen S. sclerotiorum substantially reduced lesion development. The discovery
      of poacic acid as a natural antifungal agent targeting beta-1,3-glucan highlights
      the potential side use of products generated in the processing of renewable
      biomass toward biofuels as a source of valuable bioactive compounds and further
      clarifies the nature and mechanism of fermentation inhibitors found in
      lignocellulosic hydrolysates. 

PMID- 25775514
TI  - Glucocorticoid receptor interacts with PNRC2 in a ligand-dependent manner to
      recruit UPF1 for rapid mRNA degradation.
AB  - Glucocorticoid receptor (GR), which was originally known to function as a nuclear
      receptor, plays a role in rapid mRNA degradation by acting as an RNA-binding
      protein. The mechanism by which this process occurs remains unknown. Here, we
      demonstrate that GR, preloaded onto the 5'UTR of a target mRNA, recruits UPF1
      through proline-rich nuclear receptor coregulatory protein 2 (PNRC2) in a ligand
      dependent manner, so as to elicit rapid mRNA degradation. We call this process GR
      mediated mRNA decay (GMD). Although GMD, nonsense-mediated mRNA decay (NMD), and
      staufen-mediated mRNA decay (SMD) share upstream frameshift 1 (UPF1) and PNRC2,
      we find that GMD is mechanistically distinct from NMD and SMD. We also identify
      de novo cellular GMD substrates using microarray analysis. Intriguingly, GMD
      functions in the chemotaxis of human monocytes by targeting chemokine (C-C motif)
      ligand 2 (CCL2) mRNA. Thus, our data provide molecular evidence of a
      posttranscriptional role of the well-studied nuclear hormone receptor, GR, which
      is traditionally considered a transcription factor. 

PMID- 25775516
TI  - Field experiment evidence of substantive, attributional, and behavioral
      persuasion by members of Congress in online town halls.
AB  - Do leaders persuade? Social scientists have long studied the relationship between
      elite behavior and mass opinion. However, there is surprisingly little evidence
      regarding direct persuasion by leaders. Here we show that political leaders can
      persuade their constituents directly on three dimensions: substantive attitudes
      regarding policy issues, attributions regarding the leaders' qualities, and
      subsequent voting behavior. We ran two randomized controlled field experiments
      testing the causal effects of directly interacting with a sitting politician. Our
      experiments consist of 20 online town hall meetings with members of Congress
      conducted in 2006 and 2008. Study 1 examined 19 small meetings with members of
      the House of Representatives (average 20 participants per town hall). Study 2
      examined a large (175 participants) town hall with a senator. In both experiments
      we find that participating has significant and substantively important causal
      effects on all three dimensions of persuasion but no such effects on issues that
      were not discussed extensively in the sessions. Further, persuasion was not
      driven solely by changes in copartisans' attitudes; the effects were consistent
      across groups. 

PMID- 25775515
TI  - Emergence of coherence and the dynamics of quantum phase transitions.
AB  - The dynamics of quantum phase transitions pose one of the most challenging
      problems in modern many-body physics. Here, we study a prototypical example in a
      clean and well-controlled ultracold atom setup by observing the emergence of
      coherence when crossing the Mott insulator to superfluid quantum phase
      transition. In the 1D Bose-Hubbard model, we find perfect agreement between
      experimental observations and numerical simulations for the resulting coherence
      length. We, thereby, perform a largely certified analog quantum simulation of
      this strongly correlated system reaching beyond the regime of free
      quasiparticles. Experimentally, we additionally explore the emergence of
      coherence in higher dimensions, where no classical simulations are available, as
      well as for negative temperatures. For intermediate quench velocities, we observe
      a power-law behavior of the coherence length, reminiscent of the Kibble-Zurek
      mechanism. However, we find nonuniversal exponents that cannot be captured by
      this mechanism or any other known model. 

PMID- 25775517
TI  - Conserved role of Sonic Hedgehog in tonotopic organization of the avian basilar
      papilla and mammalian cochlea.
AB  - Sound frequency discrimination begins at the organ of Corti in mammals and the
      basilar papilla in birds. Both of these hearing organs are tonotopically
      organized such that sensory hair cells at the basal (proximal) end respond to
      high frequency sound, whereas their counterparts at the apex (distal) respond to
      low frequencies. Sonic hedgehog (Shh) secreted by the developing notochord and
      floor plate is required for cochlear formation in both species. In mice, the
      apical region of the developing cochlea, closer to the ventral midline source of
      Shh, requires higher levels of Shh signaling than the basal cochlea farther away
      from the midline. Here, gain-of-function experiments using Shh-soaked beads in
      ovo or a mouse model expressing constitutively activated Smoothened (transducer
      of Shh signaling) show up-regulation of apical genes in the basal cochlea, even
      though these regionally expressed genes are not necessarily conserved between the
      two species. In chicken, these altered gene expression patterns precede
      morphological and physiological changes in sensory hair cells that are typically
      associated with tonotopy such as the total number of stereocilia per hair cell
      and gene expression of an inward rectifier potassium channel, IRK1, which is a
      bona fide feature of apical hair cells in the basilar papilla. Furthermore, our
      results suggest that this conserved role of Shh in establishing cochlear tonotopy
      is initiated early in development by Shh emanating from the notochord and floor
      plate. 

PMID- 25775518
TI  - Peroxisome extensions deliver the Arabidopsis SDP1 lipase to oil bodies.
AB  - Lipid droplets/oil bodies (OBs) are lipid-storage organelles that play a crucial
      role as an energy resource in a variety of eukaryotic cells. Lipid stores are
      mobilized in the case of food deprivation or high energy demands--for example,
      during certain developmental processes in animals and plants. OB degradation is
      achieved by lipases that hydrolyze triacylglycerols (TAGs) into free fatty acids
      and glycerol. In the model plant Arabidopsis thaliana, Sugar-Dependent 1 (SDP1)
      was identified as the major TAG lipase involved in lipid reserve mobilization
      during seedling establishment. Although the enzymatic activity of SDP1 is
      associated with the membrane of OBs, its targeting to the OB surface remains
      uncharacterized. Here we demonstrate that the core retromer, a complex involved
      in protein trafficking, participates in OB biogenesis, lipid store degradation,
      and SDP1 localization to OBs. We also report an as-yet-undescribed mechanism for
      lipase transport in eukaryotic cells, with SDP1 being first localized to the
      peroxisome membrane at early stages of seedling growth and then possibly moving
      to the OB surface through peroxisome tubulations. Finally, we show that the
      timely transfer of SDP1 to the OB membrane requires a functional core retromer.
      In addition to revealing previously unidentified functions of the retromer
      complex in plant cells, our work provides unanticipated evidence for the role of
      peroxisome dynamics in interorganelle communication and protein transport.

PMID- 25775519
TI  - Environmental stress induces trinucleotide repeat mutagenesis in human cells.
AB  - The dynamic mutability of microsatellite repeats is implicated in the
      modification of gene function and disease phenotype. Studies of the enhanced
      instability of long trinucleotide repeats (TNRs)-the cause of multiple human
      diseases-have revealed a remarkable complexity of mutagenic mechanisms. Here, we
      show that cold, heat, hypoxic, and oxidative stresses induce mutagenesis of a
      long CAG repeat tract in human cells. We show that stress-response factors
      mediate the stress-induced mutagenesis (SIM) of CAG repeats. We show further that
      SIM of CAG repeats does not involve mismatch repair, nucleotide excision repair,
      or transcription, processes that are known to promote TNR mutagenesis in other
      pathways of instability. Instead, we find that these stresses stimulate DNA
      rereplication, increasing the proportion of cells with >4 C-value (C) DNA
      content. Knockdown of the replication origin-licensing factor CDT1 eliminates
      both stress-induced rereplication and CAG repeat mutagenesis. In addition, direct
      induction of rereplication in the absence of stress also increases the proportion
      of cells with >4C DNA content and promotes repeat mutagenesis. Thus,
      environmental stress triggers a unique pathway for TNR mutagenesis that likely is
      mediated by DNA rereplication. This pathway may impact normal cells as they
      encounter stresses in their environment or during development or abnormal cells
      as they evolve metastatic potential. 

PMID- 25775520
TI  - Global dispersion and local diversification of the methane seep microbiome.
AB  - Methane seeps are widespread seafloor ecosystems shaped by the emission of gas
      from seabed reservoirs. The microorganisms inhabiting methane seeps transform the
      chemical energy in methane to products that sustain rich benthic communities
      around the gas leaks. Despite the biogeochemical relevance of microbial methane
      removal at seeps, the global diversity and dispersion of seep microbiota remain
      unknown. Here we determined the microbial diversity and community structure of 23
      globally distributed methane seeps and compared these to the microbial
      communities of 54 other seafloor ecosystems, including sulfate-methane transition
      zones, hydrothermal vents, coastal sediments, and deep-sea surface and subsurface
      sediments. We found that methane seep communities show moderate levels of
      microbial richness compared with other seafloor ecosystems and harbor distinct
      bacterial and archaeal taxa with cosmopolitan distribution and key biogeochemical
      functions. The high relative sequence abundance of ANME (anaerobic methanotrophic
      archaea), as well as aerobic Methylococcales, sulfate-reducing Desulfobacterales,
      and sulfide-oxidizing Thiotrichales, matches the most favorable microbial
      metabolisms at methane seeps in terms of substrate supply and distinguishes the
      seep microbiome from other seafloor microbiomes. The key functional taxa varied
      in relative sequence abundance between different seeps due to the environmental
      factors, sediment depth and seafloor temperature. The degree of endemism of the
      methane seep microbiome suggests a high local diversification in these
      heterogeneous but long-lived ecosystems. Our results indicate that the seep
      microbiome is structured according to metacommunity processes and that few
      cosmopolitan microbial taxa mediate the bulk of methane oxidation, with global
      relevance to methane emission in the ocean. 

PMID- 25775521
TI  - Differentiation of antiinflammatory and antitumorigenic properties of stabilized
      enantiomers of thalidomide analogs.
AB  - Therapeutics developed and sold as racemates can exhibit a limited therapeutic
      index because of side effects resulting from the undesired enantiomer (distomer)
      and/or its metabolites, which at times, forces researchers to abandon valuable
      scaffolds. Therefore, most chiral drugs are developed as single enantiomers.
      Unfortunately, the development of some chirally pure drug molecules is hampered
      by rapid in vivo racemization. The class of compounds known as immunomodulatory
      drugs derived from thalidomide is developed and sold as racemates because of
      racemization at the chiral center of the 3-aminoglutarimide moiety. Herein, we
      show that replacement of the exchangeable hydrogen at the chiral center with
      deuterium allows the stabilization and testing of individual enantiomers for two
      thalidomide analogs, including CC-122, a compound currently in human clinical
      trials for hematological cancers and solid tumors. Using "deuterium-enabled
      chiral switching" (DECS), in vitro antiinflammatory differences of up to 20-fold
      are observed between the deuterium-stabilized enantiomers. In vivo, the exposure
      is dramatically increased for each enantiomer while they retain similar
      pharmacokinetics. Furthermore, the single deuterated enantiomers related to CC
      122 exhibit profoundly different in vivo responses in an NCI-H929 myeloma
      xenograft model. The (-)-deuterated enantiomer is antitumorigenic, whereas the
      (+)-deuterated enantiomer has little to no effect on tumor growth. The ability to
      stabilize and differentiate enantiomers by DECS opens up a vast window of
      opportunity to characterize the class effects of thalidomide analogs and improve
      on the therapeutic promise of other racemic compounds, including the development
      of safer therapeutics and the discovery of new mechanisms and clinical
      applications for existing therapeutics. 

PMID- 25775522
TI  - Electrical synapses connect a network of gonadotropin releasing hormone neurons
      in a cichlid fish.
AB  - Initiating and regulating vertebrate reproduction requires pulsatile release of
      gonadotropin-releasing hormone (GnRH1) from the hypothalamus. Coordinated GnRH1
      release, not simply elevated absolute levels, effects the release of pituitary
      gonadotropins that drive steroid production in the gonads. However, the
      mechanisms underlying synchronization of GnRH1 neurons are unknown. Control of
      synchronicity by gap junctions between GnRH1 neurons has been proposed but not
      previously found. We recorded simultaneously from pairs of transgenically labeled
      GnRH1 neurons in adult male Astatotilapia burtoni cichlid fish. We report that
      GnRH1 neurons are strongly and uniformly interconnected by electrical synapses
      that can drive spiking in connected cells and can be reversibly blocked by
      meclofenamic acid. Our results suggest that electrical synapses could promote
      coordinated spike firing in a cellular assemblage of GnRH1 neurons to produce the
      pulsatile output necessary for activation of the pituitary and reproduction. 

PMID- 25775523
TI  - Reprogramming of primary human Philadelphia chromosome-positive B cell acute
      lymphoblastic leukemia cells into nonleukemic macrophages.
AB  - BCR-ABL1(+) precursor B-cell acute lymphoblastic leukemia (BCR-ABL1(+) B-ALL) is
      an aggressive hematopoietic neoplasm characterized by a block in differentiation
      due in part to the somatic loss of transcription factors required for B-cell
      development. We hypothesized that overcoming this differentiation block by
      forcing cells to reprogram to the myeloid lineage would reduce the
      leukemogenicity of these cells. We found that primary human BCR-ABL1(+) B-ALL
      cells could be induced to reprogram into macrophage-like cells by exposure to
      myeloid differentiation-promoting cytokines in vitro or by transient expression
      of the myeloid transcription factor C/EBPalpha or PU.1. The resultant cells were
      clonally related to the primary leukemic blasts but resembled normal macrophages
      in appearance, immunophenotype, gene expression, and function. Most importantly,
      these macrophage-like cells were unable to establish disease in xenograft hosts,
      indicating that lineage reprogramming eliminates the leukemogenicity of BCR
      ABL1(+) B-ALL cells, and suggesting a previously unidentified therapeutic
      strategy for this disease. Finally, we determined that myeloid reprogramming may
      occur to some degree in human patients by identifying primary CD14(+)
      monocytes/macrophages in BCR-ABL1(+) B-ALL patient samples that possess the BCR
      ABL1(+) translocation and clonally recombined VDJ regions. 

PMID- 25775524
TI  - Allelic polymorphism of GIGANTEA is responsible for naturally occurring variation
      in circadian period in Brassica rapa.
AB  - GIGANTEA (GI) was originally identified by a late-flowering mutant in
      Arabidopsis, but subsequently has been shown to act in circadian period
      determination, light inhibition of hypocotyl elongation, and responses to
      multiple abiotic stresses, including tolerance to high salt and cold (freezing)
      temperature. Genetic mapping and analysis of families of heterogeneous inbred
      lines showed that natural variation in GI is responsible for a major quantitative
      trait locus in circadian period in Brassica rapa. We confirmed this conclusion by
      transgenic rescue of an Arabidopsis gi-201 loss of function mutant. The two B.
      rapa GI alleles each fully rescued the delayed flowering of Arabidopsis gi-201
      but showed differential rescue of perturbations in red light inhibition of
      hypocotyl elongation and altered cold and salt tolerance. The B. rapa R500 GI
      allele, which failed to rescue the hypocotyl and abiotic stress phenotypes,
      disrupted circadian period determination in Arabidopsis. Analysis of chimeric B.
      rapa GI alleles identified the causal nucleotide polymorphism, which results in
      an amino acid substitution (S264A) between the two GI proteins. This polymorphism
      underlies variation in circadian period, cold and salt tolerance, and red light
      inhibition of hypocotyl elongation. Loss-of-function mutations of B. rapa GI
      confer delayed flowering, perturbed circadian rhythms in leaf movement, and
      increased freezing and increased salt tolerance, consistent with effects of
      similar mutations in Arabidopsis. Collectively, these data suggest that allelic
      variation of GI-and possibly of clock genes in general-offers an attractive
      target for molecular breeding for enhanced stress tolerance and potentially for
      improved crop yield. 

PMID- 25775525
TI  - Prosurvival Bcl-2 family members reveal a distinct apoptotic identity between
      conventional and plasmacytoid dendritic cells.
AB  - Dendritic cells (DCs) are heterogeneous, comprising subsets with functional
      specializations that play distinct roles in immunity as well as immunopathology.
      We investigated the molecular control of cell survival of two main DC subsets:
      plasmacytoid DCs (pDCs) and conventional DCs (cDCs) and their dependence on
      individual antiapoptotic BCL-2 family members. Compared with cDCs, pDCs had
      higher expression of BCL-2, lower A1, and similar levels of MCL-1 and BCL-XL.
      Transgenic overexpression of BCL-2 increased the pDC pool size in vivo with only
      minor impact on cDCs. With a view to immune intervention, we tested BCL-2
      inhibitors and found that ABT-199 (the BCL-2 specific inhibitor) selectively
      killed pDCs but not cDCs. Conversely, genetic knockdown of A1 profoundly reduced
      the proportion of cDCs but not pDCs. We also found that conditional ablation of
      MCL-1 significantly reduced the size of both DC populations in mice and impeded
      DC-mediated immune responses. Thus, we revealed that the two DC types have
      different cell survival requirements. The molecular basis of survival of
      different DC subsets thus advocates the antagonism of selective BCL-2 family
      members for treating diseases pertaining to distinct DC subsets. 

PMID- 25775526
TI  - Double-stranded DNA translocase activity of transcription factor TFIIH and the
      mechanism of RNA polymerase II open complex formation.
AB  - Formation of the RNA polymerase II (Pol II) open complex (OC) requires DNA
      unwinding mediated by the transcription factor TFIIH helicase-related subunit
      XPB/Ssl2. Because XPB/Ssl2 binds DNA downstream from the location of DNA
      unwinding, it cannot function using a conventional helicase mechanism. Here we
      show that yeast TFIIH contains an Ssl2-dependent double-stranded DNA translocase
      activity. Ssl2 tracks along one DNA strand in the 5' -> 3' direction, implying it
      uses the nontemplate promoter strand to reel downstream DNA into the Pol II
      cleft, creating torsional strain and leading to DNA unwinding. Analysis of the
      Ssl2 and DNA-dependent ATPase activity of TFIIH suggests that Ssl2 has a
      processivity of approximately one DNA turn, consistent with the length of DNA
      unwound during transcription initiation. Our results can explain why maintaining
      the OC requires continuous ATP hydrolysis and the function of TFIIH in promoter
      escape. Our results also suggest that XPB/Ssl2 uses this translocase mechanism
      during DNA repair rather than physically wedging open damaged DNA. 

PMID- 25775527
TI  - Genetic and biochemical investigations of the role of MamP in redox control of
      iron biomineralization in Magnetospirillum magneticum.
AB  - Magnetotactic bacteria have evolved complex subcellular machinery to construct
      linear chains of magnetite nanocrystals that allow the host cell to sense
      direction. Each mixed-valent iron nanoparticle is mineralized from soluble iron
      within a membrane-encapsulated vesicle termed the magnetosome, which serves as a
      specialized compartment that regulates the iron, redox, and pH environment of the
      growing mineral. To dissect the biological components that control this process,
      we have carried out a genetic and biochemical study of proteins proposed to
      function in iron mineralization. In this study, we show that the redox sites of c
      type cytochromes of the Magnetospirillum magneticum AMB-1 magnetosome island,
      MamP and MamT, are essential to their physiological function and that ablation of
      one or both heme motifs leads to loss of function, suggesting that their ability
      to carry out redox chemistry in vivo is important. We also develop a method to
      heterologously express fully heme-loaded MamP from AMB-1 for in vitro biochemical
      studies, which show that its Fe(III)-Fe(II) redox couple is set at an unusual
      potential (-89 +/- 11 mV) compared with other related cytochromes involved in
      iron reduction or oxidation. Despite its low reduction potential, it remains
      competent to oxidize Fe(II) to Fe(III) and mineralize iron to produce mixed
      valent iron oxides. Finally, in vitro mineralization experiments suggest that Mms
      mineral-templating peptides from AMB-1 can modulate the iron redox chemistry of
      MamP. 

PMID- 25775530
TI  - Methane transport from the active layer to lakes in the Arctic using Toolik Lake,
      Alaska, as a case study.
AB  - Methane emissions in the Arctic are important, and may be contributing to global
      warming. While methane emission rates from Arctic lakes are well documented,
      methods are needed to quantify the relative contribution of active layer
      groundwater to the overall lake methane budget. Here we report measurements of
      natural tracers of soil/groundwater, radon, and radium, along with methane
      concentration in Toolik Lake, Alaska, to evaluate the role active layer water
      plays as an exogenous source for lake methane. Average concentrations of methane,
      radium, and radon were all elevated in the active layer compared with lake water
      (1.6 * 10(4) nM, 61.6 dpm?m(-3), and 4.5 * 10(5) dpm?m(-3) compared with 1.3 *
      10(2) nM, 5.7 dpm?m(-3), and 4.4 * 10(3) dpm?m(-3), respectively). Methane
      transport from the active layer to Toolik Lake based on the geochemical tracer
      radon (up to 2.9 g?m(-2)?y(-1)) can account for a large fraction of methane
      emissions from this lake. Strong but spatially and temporally variable
      correlations between radon activity and methane concentrations (r(2) > 0.69) in
      lake water suggest that the parameters that control methane discharge from the
      active layer also vary. Warming in the Arctic may expand the active layer and
      increase the discharge, thereby increasing the methane flux to lakes and from
      lakes to the atmosphere, exacerbating global warming. More work is needed to
      quantify and elucidate the processes that control methane fluxes from the active
      layer to predict how this flux might change in the future and to evaluate the
      regional and global contribution of active layer water associated methane inputs.

PMID- 25775528
TI  - Heteromerization of chemokine (C-X-C motif) receptor 4 with alpha1A/B-adrenergic
      receptors controls alpha1-adrenergic receptor function.
AB  - Recent evidence suggests that chemokine (C-X-C motif) receptor 4 (CXCR4)
      contributes to the regulation of blood pressure through interactions with alpha1
      adrenergic receptors (ARs) in vascular smooth muscle. The underlying molecular
      mechanisms, however, are unknown. Using proximity ligation assays to visualize
      single-molecule interactions, we detected that alpha1A/B-ARs associate with CXCR4
      on the cell surface of rat and human vascular smooth muscle cells (VSMC).
      Furthermore, alpha1A/B-AR could be coimmunoprecipitated with CXCR4 in a HeLa
      expression system and in human VSMC. A peptide derived from the second
      transmembrane helix of CXCR4 induced chemical shift changes in the NMR spectrum
      of CXCR4 in membranes, disturbed the association between alpha1A/B-AR and CXCR4,
      and inhibited Ca(2+) mobilization, myosin light chain (MLC) 2 phosphorylation,
      and contraction of VSMC upon alpha1-AR activation. CXCR4 silencing reduced
      alpha1A/B-AR:CXCR4 heteromeric complexes in VSMC and abolished phenylephrine
      induced Ca(2+) fluxes and MLC2 phosphorylation. Treatment of rats with CXCR4
      agonists (CXCL12, ubiquitin) reduced the EC50 of the phenylephrine-induced blood
      pressure response three- to fourfold. These observations suggest that disruption
      of the quaternary structure of alpha1A/B-AR:CXCR4 heteromeric complexes by
      targeting transmembrane helix 2 of CXCR4 and depletion of the heteromeric
      receptor complexes by CXCR4 knockdown inhibit alpha1-AR-mediated function in VSMC
      and that activation of CXCR4 enhances the potency of alpha1-AR agonists. Our
      findings extend the current understanding of the molecular mechanisms regulating
      alpha1-AR and provide an example of the importance of G protein-coupled receptor
      (GPCR) heteromerization for GPCR function. Compounds targeting the alpha1A/B
      AR:CXCR4 interaction could provide an alternative pharmacological approach to
      modulate blood pressure. 

PMID- 25775529
TI  - Regulation of Nrf2 signaling and longevity in naturally long-lived rodents.
AB  - The preternaturally long-lived naked mole-rat, like other long-lived species and
      experimental models of extended longevity, is resistant to both endogenous (e.g.,
      reactive oxygen species) and environmental stressors and also resists age-related
      diseases such as cancer, cardiovascular disease, and neurodegeneration. The
      mechanisms behind the universal resilience of longer-lived organisms to stress,
      however, remain elusive. We hypothesize that this resilience is linked to the
      activity of a highly conserved transcription factor, nuclear factor erythroid 2
      related factor (Nrf2). Nrf2 regulates the transcription of several hundred
      cytoprotective molecules, including antioxidants, detoxicants, and molecular
      chaperones (heat shock proteins). Nrf2 itself is tightly regulated by mechanisms
      that either promote its activity or increase its degradation. We used a
      comparative approach and examined Nrf2-signaling activity in naked mole-rats and
      nine other rodent species with varying maximum lifespan potential (MLSP). We
      found that constitutive Nrf2-signaling activity was positively correlated (P =
      0.0285) with MLSP and that this activity was also manifested in high levels of
      downstream gene expression and activity. Surprisingly, we found that species
      longevity was not linked to the protein levels of Nrf2 itself, but rather showed
      a significant (P < 0.01) negative relationship with the regulators Kelch-like ECH
      Associated Protein 1 (Keap1) and beta-transducin repeat-containing protein
      (betaTrCP), which target Nrf2 for degradation. These findings highlight the use
      of a comparative biology approach for the identification of evolved mechanisms
      that contribute to health span, aging, and longevity. 

PMID- 25775531
TI  - Toward a mineral physics reference model for the Moon's core.
AB  - The physical properties of iron (Fe) at high pressure and high temperature are
      crucial for understanding the chemical composition, evolution, and dynamics of
      planetary interiors. Indeed, the inner structures of the telluric planets all
      share a similar layered nature: a central metallic core composed mostly of iron,
      surrounded by a silicate mantle, and a thin, chemically differentiated crust. To
      date, most studies of iron have focused on the hexagonal closed packed (hcp, or
      epsilon) phase, as epsilon-Fe is likely stable across the pressure and
      temperature conditions of Earth's core. However, at the more moderate pressures
      characteristic of the cores of smaller planetary bodies, such as the Moon,
      Mercury, or Mars, iron takes on a face-centered cubic (fcc, or gamma) structure.
      Here we present compressional and shear wave sound velocity and density
      measurements of gamma-Fe at high pressures and high temperatures, which are
      needed to develop accurate seismic models of planetary interiors. Our results
      indicate that the seismic velocities proposed for the Moon's inner core by a
      recent reanalysis of Apollo seismic data are well below those of gamma-Fe. Our
      dataset thus provides strong constraints to seismic models of the lunar core and
      cores of small telluric planets. This allows us to propose a direct compositional
      and velocity model for the Moon's core. 

PMID- 25775532
TI  - Equality bias impairs collective decision-making across cultures.
AB  - We tend to think that everyone deserves an equal say in a debate. This seemingly
      innocuous assumption can be damaging when we make decisions together as part of a
      group. To make optimal decisions, group members should weight their differing
      opinions according to how competent they are relative to one another; whenever
      they differ in competence, an equal weighting is suboptimal. Here, we asked how
      people deal with individual differences in competence in the context of a
      collective perceptual decision-making task. We developed a metric for estimating
      how participants weight their partner's opinion relative to their own and
      compared this weighting to an optimal benchmark. Replicated across three
      countries (Denmark, Iran, and China), we show that participants assigned nearly
      equal weights to each other's opinions regardless of true differences in their
      competence-even when informed by explicit feedback about their competence gap or
      under monetary incentives to maximize collective accuracy. This equality bias,
      whereby people behave as if they are as good or as bad as their partner, is
      particularly costly for a group when a competence gap separates its members. 

PMID- 25775533
TI  - Atrial natriuretic peptide prevents cancer metastasis through vascular
      endothelial cells.
AB  - Most patients suffering from cancer die of metastatic disease. Surgical removal
      of solid tumors is performed as an initial attempt to cure patients; however,
      surgery is often accompanied with trauma, which can promote early recurrence by
      provoking detachment of tumor cells into the blood stream or inducing systemic
      inflammation or both. We have previously reported that administration of atrial
      natriuretic peptide (ANP) during the perioperative period reduces inflammatory
      response and has a prophylactic effect on postoperative cardiopulmonary
      complications in lung cancer surgery. Here we demonstrate that cancer recurrence
      after curative surgery was significantly lower in ANP-treated patients than in
      control patients (surgery alone). ANP is known to bind specifically to NPR1 [also
      called guanylyl cyclase-A (GC-A) receptor]. In mouse models, we found that
      metastasis of GC-A-nonexpressing tumor cells (i.e., B16 mouse melanoma cells) to
      the lung was increased in vascular endothelium-specific GC-A knockout mice and
      decreased in vascular endothelium-specific GC-A transgenic mice compared with
      control mice. We examined the effect of ANP on tumor metastasis in mice treated
      with lipopolysaccharide, which mimics systemic inflammation induced by surgical
      stress. ANP inhibited the adhesion of cancer cells to pulmonary arterial and
      micro-vascular endothelial cells by suppressing the E-selectin expression that is
      promoted by inflammation. These results suggest that ANP prevents cancer
      metastasis by inhibiting the adhesion of tumor cells to inflamed endothelial
      cells. 

PMID- 25775534
TI  - Acyl-CoA oxidase complexes control the chemical message produced by
      Caenorhabditis elegans.
AB  - Caenorhabditis elegans uses ascaroside pheromones to induce development of the
      stress-resistant dauer larval stage and to coordinate various behaviors.
      Peroxisomal beta-oxidation cycles are required for the biosynthesis of the fatty
      acid-derived side chains of the ascarosides. Here we show that three acyl-CoA
      oxidases, which catalyze the first step in these beta-oxidation cycles, form
      different protein homo- and heterodimers with distinct substrate preferences.
      Mutations in the acyl-CoA oxidase genes acox-1, -2, and -3 led to specific
      defects in ascaroside production. When the acyl-CoA oxidases were expressed alone
      or in pairs and purified, the resulting acyl-CoA oxidase homo- and heterodimers
      displayed different side-chain length preferences in an in vitro activity assay.
      Specifically, an ACOX-1 homodimer controls the production of ascarosides with
      side chains with nine or fewer carbons, an ACOX-1/ACOX-3 heterodimer controls the
      production of those with side chains with seven or fewer carbons, and an ACOX-2
      homodimer controls the production of those with omega-side chains with less than
      five carbons. Our results support a biosynthetic model in which beta-oxidation
      enzymes act directly on the CoA-thioesters of ascaroside biosynthetic precursors.
      Furthermore, we identify environmental conditions, including high temperature and
      low food availability, that induce the expression of acox-2 and/or acox-3 and
      lead to corresponding changes in ascaroside production. Thus, our work uncovers
      an important mechanism by which C. elegans increases the production of the most
      potent dauer pheromones, those with the shortest side chains, under specific
      environmental conditions. 

PMID- 25775535
TI  - Environments and trypanosomiasis risks for early herders in the later Holocene of
      the Lake Victoria basin, Kenya.
AB  - Specialized pastoralism developed ~3 kya among Pastoral Neolithic Elmenteitan
      herders in eastern Africa. During this time, a mosaic of hunters and herders
      using diverse economic strategies flourished in southern Kenya. It has been
      argued that the risk for trypanosomiasis (sleeping sickness), carried by tsetse
      flies in bushy environments, had a significant influence on pastoral
      diversification and migration out of eastern Africa toward southern Africa ~2
      kya. Elmenteitan levels at Gogo Falls (ca. 1.9-1.6 kya) preserve a unique faunal
      record, including wild mammalian herbivores, domestic cattle and caprines, fish,
      and birds. It has been suggested that a bushy/woodland habitat that harbored
      tsetse fly constrained production of domestic herds and resulted in subsistence
      diversification. Stable isotope analysis of herbivore tooth enamel (n = 86) from
      this site reveals, instead, extensive C4 grazing by both domesticates and the
      majority of wild herbivores. Integrated with other ecological proxies (pollen and
      leaf wax biomarkers), these data imply an abundance of C4 grasses in the Lake
      Victoria basin at this time, and thus little risk for tsetse-related barriers to
      specialized pastoralism. These data provide empirical evidence for the existence
      of a grassy corridor through which small groups of herders could have passed to
      reach southern Africa. 

PMID- 25775536
TI  - Production and packaging of a biological arsenal: evolution of centipede venoms
      under morphological constraint.
AB  - Venom represents one of the most extreme manifestations of a chemical arms race.
      Venoms are complex biochemical arsenals, often containing hundreds to thousands
      of unique protein toxins. Despite their utility for prey capture, venoms are
      energetically expensive commodities, and consequently it is hypothesized that
      venom complexity is inversely related to the capacity of a venomous animal to
      physically subdue prey. Centipedes, one of the oldest yet least-studied venomous
      lineages, appear to defy this rule. Although scutigeromorph centipedes produce
      less complex venom than those secreted by scolopendrid centipedes, they appear to
      rely heavily on venom for prey capture. We show that the venom glands are large
      and well developed in both scutigerid and scolopendrid species, but that
      scutigerid forcipules lack the adaptations that allow scolopendrids to inflict
      physical damage on prey and predators. Moreover, we reveal that scolopendrid
      venom glands have evolved to accommodate a much larger number of secretory cells
      and, by using imaging mass spectrometry, we demonstrate that toxin production is
      heterogeneous across these secretory units. We propose that the differences in
      venom complexity between centipede orders are largely a result of morphological
      restrictions of the venom gland, and consequently there is a strong correlation
      between the morphological and biochemical complexity of this unique venom system.
      The current data add to the growing body of evidence that toxins are not
      expressed in a spatially homogenous manner within venom glands, and they suggest
      that the link between ecology and toxin evolution is more complex than previously
      thought. 

PMID- 25775537
TI  - Ribosome-SRP-FtsY cotranslational targeting complex in the closed state.
AB  - The signal recognition particle (SRP)-dependent pathway is essential for correct
      targeting of proteins to the membrane and subsequent insertion in the membrane or
      secretion. In Escherichia coli, the SRP and its receptor FtsY bind to ribosome
      nascent chain complexes with signal sequences and undergo a series of distinct
      conformational changes, which ensures accurate timing and fidelity of protein
      targeting. Initial recruitment of the SRP receptor FtsY to the SRP-RNC complex
      results in GTP-independent binding of the SRP-FtsY GTPases at the SRP RNA
      tetraloop. In the presence of GTP, a closed state is adopted by the SRP-FtsY
      complex. The cryo-EM structure of the closed state reveals an ordered SRP RNA and
      SRP M domain with a signal sequence-bound. Van der Waals interactions between the
      finger loop and ribosomal protein L24 lead to a constricted signal sequence
      binding pocket possibly preventing premature release of the signal sequence.
      Conserved M-domain residues contact ribosomal RNA helices 24 and 59. The SRP-FtsY
      GTPases are detached from the RNA tetraloop and flexible, thus liberating the
      ribosomal exit site for binding of the translocation machinery. 

PMID- 25775538
TI  - Fast sensory-motor reactions in echolocating bats to sudden changes during the
      final buzz and prey intercept.
AB  - Echolocation is an active sense enabling bats and toothed whales to orient in
      darkness through echo returns from their ultrasonic signals. Immediately before
      prey capture, both bats and whales emit a buzz with such high emission rates (>=
      180 Hz) and overall duration so short that its functional significance remains an
      enigma. To investigate sensory-motor control during the buzz of the insectivorous
      bat Myotis daubentonii, we removed prey, suspended in air or on water, before
      expected capture. The bats responded by shortening their echolocation buzz
      gradually; the earlier prey was removed down to approximately 100 ms (30 cm)
      before expected capture, after which the full buzz sequence was emitted both in
      air and over water. Bats trawling over water also performed the full capture
      behavior, but in-air capture motions were aborted, even at very late prey
      removals (<20 ms = 6 cm before expected contact). Thus, neither the buzz nor
      capture movements are stereotypical, but dynamically adapted based on sensory
      feedback. The results indicate that echolocation is controlled mainly by acoustic
      feedback, whereas capture movements are adjusted according to both acoustic and
      somatosensory feedback, suggesting separate (but coordinated) central motor
      control of the two behaviors based on multimodal input. Bat echolocation,
      especially the terminal buzz, provides a unique window to extremely fast decision
      processes in response to sensory feedback and modulation through attention in a
      naturally behaving animal.

PMID- 25775539
TI  - L-selectin shedding is activated specifically within transmigrating pseudopods of
      monocytes to regulate cell polarity in vitro.
AB  - L-selectin is a cell adhesion molecule that tethers free-flowing leukocytes from
      the blood to luminal vessel walls, facilitating the initial stages of their
      emigration from the circulation toward an extravascular inflammatory insult.
      Following shear-resistant adhesion to the vessel wall, L-selectin has frequently
      been reported to be rapidly cleaved from the plasma membrane (known as ectodomain
      shedding), with little knowledge of the timing or functional consequence of this
      event. Using advanced imaging techniques, we observe L-selectin shedding
      occurring exclusively as primary human monocytes actively engage in
      transendothelial migration (TEM). Moreover, the shedding was localized to
      transmigrating pseudopods within the subendothelial space. By capturing monocytes
      in midtransmigration, we could monitor the subcellular distribution of L-selectin
      and better understand how ectodomain shedding might contribute to TEM.
      Mechanistically, L-selectin loses association with calmodulin (CaM; a negative
      regulator of shedding) specifically within transmigrating pseudopods. In
      contrast, L-selectin/CaM interaction remained intact in nontransmigrated regions
      of monocytes. We show phosphorylation of L-selectin at Ser 364 is critical for
      CaM dissociation, which is also restricted to the transmigrating pseudopod.
      Pharmacological or genetic inhibition of L-selectin shedding significantly
      increased pseudopodial extensions in transmigrating monocytes, which potentiated
      invasive behavior during TEM and prevented the establishment of front/back
      polarity for directional migration persistence once TEM was complete. We conclude
      that L-selectin shedding directly regulates polarity in transmigrated monocytes,
      which affirms an active role for this molecule in driving later stages of the
      multistep adhesion cascade. 

PMID- 25775540
TI  - Molecular ruler determines needle length for the Salmonella Spi-1 injectisome.
AB  - The type-III secretion (T3S) systems of bacteria are part of self-assembling
      nanomachines: the bacterial flagellum that enables cells to propel themselves
      through liquid and across hydrated surfaces, and the injectisome that delivers
      pathogenic effector proteins into eukaryotic host cells. Although the flagellum
      and injectisome serve different purposes, they are evolutionarily related and
      share many structural similarities. Core features to these T3S systems are
      intrinsic length control mechanisms for external cellular projections: the hook
      of the flagellum and the injectisome needle. We present evidence that the Spi-1
      injectisome, like the Salmonella flagellar hook, uses a secreted molecular ruler,
      InvJ, to determine needle length. This result supports a universal length control
      mechanism using molecular rulers for T3S systems. 

PMID- 25775541
TI  - Herpes simplex viral-vector design for efficient transduction of nonneuronal
      cells without cytotoxicity.
AB  - The design of highly defective herpes simplex virus (HSV) vectors for transgene
      expression in nonneuronal cells in the absence of toxic viral-gene activity has
      been elusive. Here, we report that elements of the latency locus protect a
      nonviral promoter against silencing in primary human cells in the absence of any
      viral-gene expression. We identified a CTCF motif cluster 5' to the latency
      promoter and a known long-term regulatory region as important elements for
      vigorous transgene expression from a vector that is functionally deleted for all
      five immediate-early genes and the 15-kb internal repeat region. We inserted a
      16.5-kb expression cassette for full-length mouse dystrophin and report robust
      and durable expression in dystrophin-deficient muscle cells in vitro. Given the
      broad cell tropism of HSV, our design provides a nontoxic vector that can
      accommodate large transgene constructs for transduction of a wide variety of
      cells without vector integration, thereby filling an important void in the
      current arsenal of gene-therapy vectors. 

PMID- 25775542
TI  - Intercellular signaling via cyclic GMP diffusion through gap junctions restarts
      meiosis in mouse ovarian follicles.
AB  - Meiosis in mammalian oocytes is paused until luteinizing hormone (LH) activates
      receptors in the mural granulosa cells of the ovarian follicle. Prior work has
      established the central role of cyclic GMP (cGMP) from the granulosa cells in
      maintaining meiotic arrest, but it is not clear how binding of LH to receptors
      that are located up to 10 cell layers away from the oocyte lowers oocyte cGMP and
      restarts meiosis. Here, by visualizing intercellular trafficking of cGMP in real
      time in live follicles from mice expressing a FRET sensor, we show that diffusion
      of cGMP through gap junctions is responsible not only for maintaining meiotic
      arrest, but also for rapid transmission of the signal that reinitiates meiosis
      from the follicle surface to the oocyte. Before LH exposure, the cGMP
      concentration throughout the follicle is at a uniformly high level of ~2-4 MUM.
      Then, within 1 min of LH application, cGMP begins to decrease in the peripheral
      granulosa cells. As a consequence, cGMP from the oocyte diffuses into the sink
      provided by the large granulosa cell volume, such that by 20 min the cGMP
      concentration in the follicle is uniformly low, ~100 nM. The decrease in cGMP in
      the oocyte relieves the inhibition of the meiotic cell cycle. This direct
      demonstration that a physiological signal initiated by a stimulus in one region
      of an intact tissue can travel across many layers of cells via cyclic nucleotide
      diffusion through gap junctions could provide a general mechanism for diverse
      cellular processes. 

PMID- 25775543
TI  - Activation of the factor XII-driven contact system in Alzheimer's disease patient
      and mouse model plasma.
AB  - Alzheimer's disease (AD) is characterized by accumulation of the beta-amyloid
      peptide (Abeta), which likely contributes to disease via multiple mechanisms.
      Increasing evidence implicates inflammation in AD, the origins of which are not
      completely understood. We investigated whether circulating Abeta could initiate
      inflammation in AD via the plasma contact activation system. This proteolytic
      cascade is triggered by the activation of the plasma protein factor XII (FXII)
      and leads to kallikrein-mediated cleavage of high molecular-weight kininogen (HK)
      and release of proinflammatory bradykinin. Abeta has been shown to promote FXII
      dependent cleavage of HK in vitro. In addition, increased cleavage of HK has been
      found in the cerebrospinal fluid of patients with AD. Here, we show increased
      activation of FXII, kallikrein activity, and HK cleavage in AD patient plasma.
      Increased contact system activation is also observed in AD mouse model plasma and
      in plasma from wild-type mice i.v. injected with Abeta42. Our results demonstrate
      that Abeta42-mediated contact system activation can occur in the AD circulation
      and suggest new pathogenic mechanisms, diagnostic tests, and therapies for AD. 

PMID- 25775544
TI  - The effects of reputational and social knowledge on cooperation.
AB  - The emergence and sustenance of cooperative behavior is fundamental for a society
      to thrive. Recent experimental studies have shown that cooperation increases in
      dynamic networks in which subjects can choose their partners. However, these
      studies did not vary reputational knowledge, or what subjects know about other's
      past actions, which has long been recognized as an important factor in supporting
      cooperation. They also did not give subjects access to global social knowledge,
      or information on who is connected to whom in the group. As a result, it remained
      unknown how reputational and social knowledge foster cooperative behavior in
      dynamic networks both independently and by complementing each other. In an
      experimental setting, we show that global reputational knowledge is crucial to
      sustaining a high level of cooperation and welfare. Cooperation is associated
      with the emergence of dense and clustered networks with highly cooperative hubs.
      Global social knowledge has no effect on the aggregate level of cooperation. A
      community analysis shows that the addition of global social knowledge to global
      reputational knowledge affects the distribution of cooperative activity:
      cooperators form a separate community that achieves a higher cooperation level
      than the community of defectors. Members of the community of cooperators achieve
      a higher payoff from interactions within the community than members of the less
      cooperative community. 

PMID- 25775545
TI  - ATM prevents DSB formation by coordinating SSB repair and cell cycle progression.
AB  - DNA single-strand breaks (SSBs) arise as a consequence of spontaneous DNA
      instability and are also formed as DNA repair intermediates. Their repair is
      critical because they otherwise terminate gene transcription and generate toxic
      DNA double-strand breaks (DSBs) on replication. To prevent the formation of DSBs,
      SSB repair must be completed before DNA replication. To accomplish this, cells
      should be able to detect unrepaired SSBs, and then delay cell cycle progression
      to allow more time for repair; however, to date there is no evidence supporting
      the coordination of SSB repair and replication in human cells. Here we report
      that ataxia-telangiectasia mutated kinase (ATM) plays a major role in restricting
      the replication of SSB-containing DNA and thus prevents DSB formation. We show
      that ATM is activated by SSBs and coordinates their repair with DNA replication.
      SSB-mediated ATM activation is followed by a G1 cell cycle delay that allows more
      time for repair and thus prevents the replication of damaged DNA and DSB accrual.
      These findings establish an unanticipated role for ATM in the signaling of DNA
      SSBs and provide important insight into the molecular defects leading to genetic
      instability in patients with ataxia-telangiectasia. 

PMID- 25775546
TI  - Neuropeptide Y stimulates autophagy in hypothalamic neurons.
AB  - Aging is characterized by autophagy impairment that contributes to age-related
      disease aggravation. Moreover, it was described that the hypothalamus is a
      critical brain area for whole-body aging development and has impact on lifespan.
      Neuropeptide Y (NPY) is one of the major neuropeptides present in the
      hypothalamus, and it has been shown that, in aged animals, the hypothalamic NPY
      levels decrease. Because caloric restriction (CR) delays aging, at least in part,
      by stimulating autophagy, and also increases hypothalamic NPY levels, we
      hypothesized that NPY could have a relevant role on autophagy modulation in the
      hypothalamus. Therefore, the aim of this study was to investigate the role of NPY
      on autophagy in the hypothalamus. Using both hypothalamic neuronal in vitro
      models and mice overexpressing NPY in the hypothalamus, we observed that NPY
      stimulates autophagy in the hypothalamus. Mechanistically, in rodent hypothalamic
      neurons, NPY increases autophagy through the activation of NPY Y1 and Y5
      receptors, and this effect is tightly associated with the concerted activation of
      PI3K, MEK/ERK, and PKA signaling pathways. Modulation of hypothalamic NPY levels
      may be considered a potential strategy to produce protective effects against
      hypothalamic impairments associated with age and to delay aging. 

PMID- 25775547
TI  - Functionally conserved architecture of hepatitis C virus RNA genomes.
AB  - Hepatitis C virus (HCV) infects over 170 million people worldwide and is a
      leading cause of liver disease and cancer. The virus has a 9,650-nt, single
      stranded, messenger-sense RNA genome that is infectious as an independent entity.
      The RNA genome has evolved in response to complex selection pressures, including
      the need to maintain structures that facilitate replication and to avoid
      clearance by cell-intrinsic immune processes. Here we used high-throughput,
      single-nucleotide resolution information to generate and functionally test data
      driven structural models for three diverse HCV RNA genomes. We identified, de
      novo, multiple regions of conserved RNA structure, including all previously
      characterized cis-acting regulatory elements and also multiple novel structures
      required for optimal viral fitness. Well-defined RNA structures in the central
      regions of HCV genomes appear to facilitate persistent infection by masking the
      genome from RNase L and double-stranded RNA-induced innate immune sensors. This
      work shows how structure-first comparative analysis of entire genomes of a
      pathogenic RNA virus enables comprehensive and concise identification of
      regulatory elements and emphasizes the extensive interrelationships among RNA
      genome structure, viral biology, and innate immune responses. 

PMID- 25775548
TI  - Altered cofactor regulation with disease-associated p97/VCP mutations.
AB  - Dominant mutations in p97/VCP (valosin-containing protein) cause a rare
      multisystem degenerative disease with varied phenotypes that include inclusion
      body myopathy, Paget's disease of bone, frontotemporal dementia, and amyotrophic
      lateral sclerosis. p97 disease mutants have altered N-domain conformations,
      elevated ATPase activity, and altered cofactor association. We have now
      discovered a previously unidentified disease-relevant functional property of p97
      by identifying how the cofactors p37 and p47 regulate p97 ATPase activity. We
      define p37 as, to our knowledge, the first known p97-activating cofactor, which
      enhances the catalytic efficiency (kcat/Km) of p97 by 11-fold. Whereas both p37
      and p47 decrease the Km of ATP in p97, p37 increases the kcat of p97. In
      contrast, regulation by p47 is biphasic, with decreased kcat at low levels but
      increased kcat at higher levels. By deleting a region of p47 that lacks homology
      to p37 (amino acids 69-92), we changed p47 from an inhibitory cofactor to an
      activating cofactor, similar to p37. Our data suggest that cofactors regulate p97
      ATPase activity by binding to the N domain. Induced conformation changes affect
      ADP/ATP binding at the D1 domain, which in turn controls ATPase cycling. Most
      importantly, we found that the D2 domain of disease mutants failed to be
      activated by p37 or p47. Our results show that cofactors play a critical role in
      controlling p97 ATPase activity, and suggest that lack of cofactor-regulated
      communication may contribute to p97-associated disease pathogenesis. 

PMID- 25775549
TI  - Genome-wide analysis of thylakoid-bound ribosomes in maize reveals principles of
      cotranslational targeting to the thylakoid membrane.
AB  - Chloroplast genomes encode ~ 37 proteins that integrate into the thylakoid
      membrane. The mechanisms that target these proteins to the membrane are largely
      unexplored. We used ribosome profiling to provide a comprehensive, high
      resolution map of ribosome positions on chloroplast mRNAs in separated membrane
      and soluble fractions in maize seedlings. The results show that translation
      invariably initiates off the thylakoid membrane and that ribosomes synthesizing a
      subset of membrane proteins subsequently become attached to the membrane in a
      nuclease-resistant fashion. The transition from soluble to membrane-attached
      ribosomes occurs shortly after the first transmembrane segment in the nascent
      peptide has emerged from the ribosome. Membrane proteins whose translation
      terminates before emergence of a transmembrane segment are translated in the
      stroma and targeted to the membrane posttranslationally. These results indicate
      that the first transmembrane segment generally comprises the signal that links
      ribosomes to thylakoid membranes for cotranslational integration. The sole
      exception is cytochrome f, whose cleavable N-terminal cpSecA-dependent signal
      sequence engages the thylakoid membrane cotranslationally. The distinct behavior
      of ribosomes synthesizing the inner envelope protein CemA indicates that sorting
      signals for the thylakoid and envelope membranes are distinguished
      cotranslationally. In addition, the fractionation behavior of ribosomes in
      polycistronic transcription units encoding both membrane and soluble proteins
      adds to the evidence that the removal of upstream ORFs by RNA processing is not
      typically required for the translation of internal genes in polycistronic
      chloroplast mRNAs.

PMID- 25775550
TI  - Soft, curved electrode systems capable of integration on the auricle as a
      persistent brain-computer interface.
AB  - Recent advances in electrodes for noninvasive recording of electroencephalograms
      expand opportunities collecting such data for diagnosis of neurological disorders
      and brain-computer interfaces. Existing technologies, however, cannot be used
      effectively in continuous, uninterrupted modes for more than a few days due to
      irritation and irreversible degradation in the electrical and mechanical
      properties of the skin interface. Here we introduce a soft, foldable collection
      of electrodes in open, fractal mesh geometries that can mount directly and
      chronically on the complex surface topology of the auricle and the mastoid, to
      provide high-fidelity and long-term capture of electroencephalograms in ways that
      avoid any significant thermal, electrical, or mechanical loading of the skin.
      Experimental and computational studies establish the fundamental aspects of the
      bending and stretching mechanics that enable this type of intimate integration on
      the highly irregular and textured surfaces of the auricle. Cell level tests and
      thermal imaging studies establish the biocompatibility and wearability of such
      systems, with examples of high-quality measurements over periods of 2 wk with
      devices that remain mounted throughout daily activities including vigorous
      exercise, swimming, sleeping, and bathing. Demonstrations include a text speller
      with a steady-state visually evoked potential-based brain-computer interface and
      elicitation of an event-related potential (P300 wave). 

PMID- 25775552
TI  - Propensity of undulatory swimmers, such as worms, to go against the flow.
AB  - The ability to orient oneself in response to environmental cues is crucial to the
      survival and function of diverse organisms. One such orientation behavior is the
      alignment of aquatic organisms with (negative rheotaxis) or against (positive
      rheotaxis) fluid current. The questions of whether low-Reynolds-number,
      undulatory swimmers, such as worms, rheotax and whether rheotaxis is a deliberate
      or an involuntary response to mechanical forces have been the subject of
      conflicting reports. To address these questions, we use Caenorhabditis elegans as
      a model undulatory swimmer and examine, in experiment and theory, the orientation
      of C. elegans in the presence of flow. We find that when close to a stationary
      surface the animal aligns itself against the direction of the flow. We elucidate
      for the first time to our knowledge the mechanisms of rheotaxis in worms and show
      that rheotaxis can be explained solely by mechanical forces and does not require
      sensory input or deliberate action. The interaction between the flow field
      induced by the swimmer and a nearby surface causes the swimmer to tilt toward the
      surface and the velocity gradient associated with the flow rotates the animal to
      face upstream. Fluid mechanical computer simulations faithfully mimic the
      behavior observed in experiments, supporting the notion that rheotaxis behavior
      can be fully explained by hydrodynamics. Our study highlights the important role
      of hydrodynamics in the behavior of small undulating swimmers and may assist in
      developing control strategies to affect the animals' life cycles. 

PMID- 25775551
TI  - Vaccine composition formulated with a novel TLR7-dependent adjuvant induces high
      and broad protection against Staphylococcus aureus.
AB  - Both active and passive immunization strategies against Staphylococcus aureus
      have thus far failed to show efficacy in humans. With the attempt to develop an
      effective S. aureus vaccine, we selected five conserved antigens known to have
      different roles in S. aureus pathogenesis. They include the secreted factors
      alpha-hemolysin (Hla), ess extracellular A (EsxA), and ess extracellular B (EsxB)
      and the two surface proteins ferric hydroxamate uptake D2 and conserved
      staphylococcal antigen 1A. The combined vaccine antigens formulated with aluminum
      hydroxide induced antibodies with opsonophagocytic and functional activities and
      provided consistent protection in four mouse models when challenged with a panel
      of epidemiologically relevant S. aureus strains. The importance of antibodies in
      protection was demonstrated by passive transfer experiments. Furthermore, when
      formulated with a toll-like receptor 7-dependent (TLR7) agonist recently designed
      and developed in our laboratories (SMIP.7-10) adsorbed to alum, the five antigens
      provided close to 100% protection against four different staphylococcal strains.
      The new formulation induced not only high antibody titers but also a Th1 skewed
      immune response as judged by antibody isotype and cytokine profiles. In addition,
      low frequencies of IL-17-secreting T cells were also observed. Altogether, our
      data demonstrate that the rational selection of mixtures of conserved antigens
      combined with Th1/Th17 adjuvants can lead to promising vaccine formulations
      against S. aureus. 

PMID- 25775553
TI  - Synchronous down-modulation of miR-17 family members is an early causative event
      in the retinal angiogenic switch.
AB  - Six members of the microRNA-17 (miR-17) family were mapped to three different
      chromosomes, although they share the same seed sequence and are predicted to
      target common genes, among which are those encoding hypoxia-inducible factor
      1alpha (HIF1A) and VEGFA. Here, we evaluated the in vivo expression profile of
      the miR-17 family in the murine retinopathy of prematurity (ROP) model, whereby
      Vegfa expression is highly enhanced at the early stage of retinal
      neovascularization, and we found simultaneous reduction of all miR-17 family
      members at this stage. Using gene reporter assays, we observed binding of these
      miRs to specific sites in the 3' UTRs of Hif1a and Vegfa. Furthermore,
      overexpression of these miRs decreased HIF1A and VEGFA expression in vitro. Our
      data indicate that this miR-17 family elicits a regulatory synergistic down
      regulation of Hif1a and Vegfa expression in this biological model. We propose the
      existence of a coordinated regulatory network, in which diverse miRs are
      synchronously regulated to target the Hif1a transcription factor, which in turn,
      potentiates and reinforces the regulatory effects of the miRs on Vegfa to trigger
      and sustain a significant physiological response. 

PMID- 25775554
TI  - Submarine groundwater discharge as a major source of nutrients to the
      Mediterranean Sea.
AB  - The Mediterranean Sea (MS) is a semienclosed basin that is considered one of the
      most oligotrophic seas in the world. In such an environment, inputs of
      allochthonous nutrients and micronutrients play an important role in sustaining
      primary productivity. Atmospheric deposition and riverine runoff have been
      traditionally considered the main external sources of nutrients to the MS,
      whereas the role of submarine groundwater discharge (SGD) has been largely
      ignored. However, given the large Mediterranean shore length relative to its
      surface area, SGD may be a major conveyor of dissolved compounds to the MS. Here,
      we used a (228)Ra mass balance to demonstrate that the total SGD contributes up
      to (0.3-4.8)?10(12) m(3) ? y(-1) to the MS, which appears to be equal or larger
      by a factor of 16 to the riverine discharge. SGD is also a major source of
      dissolved inorganic nutrients to the MS, with median annual fluxes of 190?10(9),
      0.7?10(9), and 110?10(9) mol for nitrogen, phosphorous, and silica, respectively,
      which are comparable to riverine and atmospheric inputs. This corroborates the
      profound implications that SGD may have for the biogeochemical cycles of the MS.
      Inputs of other dissolved compounds (e.g., iron, carbon) via SGD could also be
      significant and should be investigated.

PMID- 25775555
TI  - Computational protein design enables a novel one-carbon assimilation pathway.
AB  - We describe a computationally designed enzyme, formolase (FLS), which catalyzes
      the carboligation of three one-carbon formaldehyde molecules into one three
      carbon dihydroxyacetone molecule. The existence of FLS enables the design of a
      new carbon fixation pathway, the formolase pathway, consisting of a small number
      of thermodynamically favorable chemical transformations that convert formate into
      a three-carbon sugar in central metabolism. The formolase pathway is predicted to
      use carbon more efficiently and with less backward flux than any naturally
      occurring one-carbon assimilation pathway. When supplemented with enzymes
      carrying out the other steps in the pathway, FLS converts formate into
      dihydroxyacetone phosphate and other central metabolites in vitro. These results
      demonstrate how modern protein engineering and design tools can facilitate the
      construction of a completely new biosynthetic pathway. 

PMID- 25775557
TI  - Imperial expansion, public investment, and the long path of history: China's
      initial political unification and its aftermath.
AB  - The Neolithic (ca. 8000-1900 B.C.) underpinnings of early Chinese civilization
      had diverse geographic and cultural foundations in distinct traditions, ways of
      life, subsistence regimes, and modes of leadership. The subsequent Bronze Age
      (ca. 1900-221 B.C.) was characterized by increasing political consolidation,
      expansion, and heightened interaction, culminating in an era of a smaller number
      of warring states. During the third century B.C., the Qin Dynasty first
      politically unified this fractious landscape, across an area that covers much of
      what is now China, and rapidly instituted a series of infrastructural investments
      and other unifying measures, many of which were maintained and amplified during
      the subsequent Han Dynasty. Here, we examine this historical sequence at both the
      national and macroscale and more deeply for a small region on the coast of the
      Shandong Province, where we have conducted several decades of archaeological
      research. At both scales, we examine apparent shifts in the governance of local
      diversity and some of the implications both during Qin-Han times and for the
      longer duree. 

PMID- 25775556
TI  - AIM2 and NLRC4 inflammasomes contribute with ASC to acute brain injury
      independently of NLRP3.
AB  - Inflammation that contributes to acute cerebrovascular disease is driven by the
      proinflammatory cytokine interleukin-1 and is known to exacerbate resulting
      injury. The activity of interleukin-1 is regulated by multimolecular protein
      complexes called inflammasomes. There are multiple potential inflammasomes
      activated in diverse diseases, yet the nature of the inflammasomes involved in
      brain injury is currently unknown. Here, using a rodent model of stroke, we show
      that the NLRC4 (NLR family, CARD domain containing 4) and AIM2 (absent in
      melanoma 2) inflammasomes contribute to brain injury. We also show that acute
      ischemic brain injury is regulated by mechanisms that require ASC (apoptosis
      associated speck-like protein containing a CARD), a common adaptor protein for
      several inflammasomes, and that the NLRP3 (NLR family, pyrin domain containing 3)
      inflammasome is not involved in this process. These discoveries identify the
      NLRC4 and AIM2 inflammasomes as potential therapeutic targets for stroke and
      provide new insights into how the inflammatory response is regulated after an
      acute injury to the brain. 

PMID- 25775558
TI  - Early Roman military fortifications and the origin of Trieste, Italy.
AB  - An interdisciplinary study of the archaeological landscape of the Trieste area
      (northeastern Italy), mainly based on airborne light detection and ranging
      (LiDAR), ground penetrating radar (GPR), and archaeological surveys, has led to
      the discovery of an early Roman fortification system, composed of a big central
      camp (San Rocco) flanked by two minor forts. The most ancient archaeological
      findings, including a Greco-Italic amphora rim produced in Latium or Campania,
      provide a relative chronology for the first installation of the structures
      between the end of the third century B.C. and the first decades of the second
      century B.C. whereas other materials, such as Lamboglia 2 amphorae and a military
      footwear hobnail (type D of Alesia), indicate that they maintained a strategic
      role at least up to the mid first century B.C. According to archaeological data
      and literary sources, the sites were probably established in connection with the
      Roman conquest of the Istria peninsula in 178-177 B.C. They were in use, perhaps
      not continuously, at least until the foundation of Tergeste, the ancestor of
      Trieste, in the mid first century B.C. The San Rocco site, with its exceptional
      size and imposing fortifications, is the main known Roman evidence of the Trieste
      area during this phase and could correspond to the location of the first
      settlement of Tergeste preceding the colony foundation. This hypothesis would
      also be supported by literary sources that describe it as a phrourion (Strabo, V,
      1, 9, C 215), a term used by ancient writers to designate the fortifications of
      the Roman army. 

PMID- 25775559
TI  - Reverse switching of surface roughness in a self-organized polydomain liquid
      crystal coating.
AB  - In this work we propose randomly ordered polydomain nematic liquid crystal
      polymer networks to reversibly generate notable jagged relief patterns at a
      polymer coating surface by light illumination. The domain size is controlled by
      the addition of traces of partly insoluble fluorinated acrylate. The
      photoresponse of the coating is induced by a small amount of copolymerized
      azobenzene monomers. Upon exposure to UV light, azobenzene undergoes trans to cis
      isomerization, resulting in a change in molecular order and packing within each
      domain. The extent of this effect and its directionality depends on the domain
      orientation. Localized to domain level, this morphological change forms large 3D
      spikes at the surface with a modulation amplitude of more than 20% of the initial
      thickness. The process is reversible; the surface topographical patterns erase
      within 10 s by stopping the light exposure. A finite element model is applied to
      simulate the surface topography changes of the polydomain coating. The
      simulations describe the formation of the topographic features in terms of light
      absorption and isomerization process as a function of the director orientation.
      The random director distribution leads to surface structures which were found to
      be in close agreement with the ones measured by interference microscopy. The
      effect of domain size on surface roughness and depth modulation was explored and
      related to the internal mechanical constraints. The use of nematic liquid crystal
      polydomains confined in a polymer network largely simplifies the fabrication of
      smart coatings with a prominent triggered topographic response. 

PMID- 25775560
TI  - Structural mechanism of sensing long dsRNA via a noncatalytic domain in human
      oligoadenylate synthetase 3.
AB  - The mammalian innate immune system uses several sensors of double-stranded RNA
      (dsRNA) to develop the interferon response. Among these sensors are dsRNA
      activated oligoadenylate synthetases (OAS), which produce signaling 2',5'-linked
      RNA molecules (2-5A) that activate regulated RNA decay in mammalian tissues.
      Different receptors from the OAS family contain one, two, or three copies of the
      2-5A synthetase domain, which in several instances evolved into pseudoenzymes.
      The structures of the pseudoenzymatic domains and their roles in sensing dsRNA
      are unknown. Here we present the crystal structure of the first catalytically
      inactive domain of human OAS3 (hOAS3.DI) in complex with a 19-bp dsRNA,
      determined at 2.0-A resolution. The conformation of hOAS3.DI is different from
      the apo- and the dsRNA-bound states of the catalytically active homolog, OAS1,
      reported previously. The unique conformation of hOAS3.DI disables 2-5A synthesis
      by placing the active site residues nonproductively, but favors the binding of
      dsRNA. Biochemical data show that hOAS3.DI is essential for activation of hOAS3
      and serves as a dsRNA-binding module, whereas the C-terminal domain DIII carries
      out catalysis. The location of the dsRNA-binding domain (DI) and the catalytic
      domain (DIII) at the opposite protein termini makes hOAS3 selective for long
      dsRNA. This mechanism relies on the catalytic inactivity of domain DI, revealing
      a surprising role of pseudoenzyme evolution in dsRNA surveillance. 

PMID- 25775561
TI  - Folliculin-interacting proteins Fnip1 and Fnip2 play critical roles in kidney
      tumor suppression in cooperation with Flcn.
AB  - Folliculin (FLCN)-interacting proteins 1 and 2 (FNIP1, FNIP2) are homologous
      binding partners of FLCN, a tumor suppressor for kidney cancer. Recent studies
      have revealed potential functions for Flcn in kidney; however, kidney-specific
      functions for Fnip1 and Fnip2 are unknown. Here we demonstrate that Fnip1 and
      Fnip2 play critical roles in kidney tumor suppression in cooperation with Flcn.
      We observed no detectable phenotype in Fnip2 knockout mice, whereas Fnip1
      deficiency produced phenotypes similar to those seen in Flcn-deficient mice in
      multiple organs, but not in kidneys. We found that absolute Fnip2 mRNA copy
      number was low relative to Fnip1 in organs that showed phenotypes under Fnip1
      deficiency but was comparable to Fnip1 mRNA copy number in mouse kidney.
      Strikingly, kidney-targeted Fnip1/Fnip2 double inactivation produced enlarged
      polycystic kidneys, as was previously reported in Flcn-deficient kidneys. Kidney
      specific Flcn inactivation did not further augment kidney size or cystic
      histology of Fnip1/Fnip2 double-deficient kidneys, suggesting pathways
      dysregulated in Flcn-deficient kidneys and Fnip1/Fnip2 double-deficient kidneys
      are convergent. Heterozygous Fnip1/homozygous Fnip2 double-knockout mice
      developed kidney cancer at 24 mo of age, analogous to the heterozygous Flcn
      knockout mouse model, further supporting the concept that Fnip1 and Fnip2 are
      essential for the tumor-suppressive function of Flcn and that kidney
      tumorigenesis in human Birt-Hogg-Dube syndrome may be triggered by loss of
      interactions among Flcn, Fnip1, and Fnip2. Our findings uncover important roles
      for Fnip1 and Fnip2 in kidney tumor suppression and may provide molecular targets
      for the development of novel therapeutics for kidney cancer. 

PMID- 25775562
TI  - New aspect of plant-rhizobia interaction: alkaloid biosynthesis in Crotalaria
      depends on nodulation.
AB  - Infection of legume hosts by rhizobial bacteria results in the formation of a
      specialized organ, the nodule, in which atmospheric nitrogen is reduced to
      ammonia. Nodulation requires the reprogramming of the plant cell, allowing the
      microsymbiont to enter the plant tissue in a highly controlled manner. We have
      found that, in Crotalaria (Fabaceae), this reprogramming is associated with the
      biosynthesis of pyrrolizidine alkaloids (PAs). These compounds are part of the
      plant's chemical defense against herbivores and cannot be regarded as being
      functionally involved in the symbiosis. PAs in Crotalaria are detectable only
      when the plants form nodules after infection with their rhizobial partner. The
      identification of a plant-derived sequence encoding homospermidine synthase
      (HSS), the first pathway-specific enzyme of PA biosynthesis, suggests that the
      plant and not the microbiont is the producer of PAs. Transcripts of HSS are
      detectable exclusively in the nodules, the tissue with the highest concentration
      of PAs, indicating that PA biosynthesis is restricted to the nodules and that the
      nodules are the source from which the alkaloids are transported to the above
      ground parts of the plant. The link between nodulation and the biosynthesis of
      nitrogen-containing alkaloids in Crotalaria highlights a further facet of the
      effect of symbiosis with rhizobia on the ecologically important trait of the
      plant's chemical defense. 

PMID- 25775563
TI  - Essential genome of Pseudomonas aeruginosa in cystic fibrosis sputum.
AB  - Defining the essential genome of bacterial pathogens is central to developing an
      understanding of the biological processes controlling disease. This has proven
      elusive for Pseudomonas aeruginosa during chronic infection of the cystic
      fibrosis (CF) lung. In this paper, using a Monte Carlo simulation-based method to
      analyze high-throughput transposon sequencing data, we establish the P.
      aeruginosa essential genome with statistical precision in laboratory media and CF
      sputum. Reconstruction of the global requirements for growth in CF sputum
      compared with defined growth conditions shows that the latter requires several
      cofactors including biotin, riboflavin, and pantothenate. Comparison of P.
      aeruginosa strains PAO1 and PA14 demonstrates that essential genes are primarily
      restricted to the core genome; however, some orthologous genes in these strains
      exhibit differential essentiality. These results indicate that genes with similar
      molecular functions may have distinct genetic roles in different P. aeruginosa
      strains during growth in CF sputum. We also show that growth in a defined growth
      medium developed to mimic CF sputum yielded virtually identical fitness
      requirements to CF sputum, providing support for this medium as a relevant in
      vitro model for CF microbiology studies. 

PMID- 25775564
TI  - Quantitative modeling of transcription factor binding specificities using DNA
      shape.
AB  - DNA binding specificities of transcription factors (TFs) are a key component of
      gene regulatory processes. Underlying mechanisms that explain the highly specific
      binding of TFs to their genomic target sites are poorly understood. A better
      understanding of TF-DNA binding requires the ability to quantitatively model TF
      binding to accessible DNA as its basic step, before additional in vivo components
      can be considered. Traditionally, these models were built based on nucleotide
      sequence. Here, we integrated 3D DNA shape information derived with a high
      throughput approach into the modeling of TF binding specificities. Using support
      vector regression, we trained quantitative models of TF binding specificity based
      on protein binding microarray (PBM) data for 68 mammalian TFs. The evaluation of
      our models included cross-validation on specific PBM array designs, testing
      across different PBM array designs, and using PBM-trained models to predict
      relative binding affinities derived from in vitro selection combined with deep
      sequencing (SELEX-seq). Our results showed that shape-augmented models compared
      favorably to sequence-based models. Although both k-mer and DNA shape features
      can encode interdependencies between nucleotide positions of the binding site,
      using DNA shape features reduced the dimensionality of the feature space. In
      addition, analyzing the feature weights of DNA shape-augmented models uncovered
      TF family-specific structural readout mechanisms that were not revealed by the
      DNA sequence. As such, this work combines knowledge from structural biology and
      genomics, and suggests a new path toward understanding TF binding and genome
      function. 

PMID- 25775565
TI  - Latent structure in random sequences drives neural learning toward a rational
      bias.
AB  - People generally fail to produce random sequences by overusing alternating
      patterns and avoiding repeating ones-the gambler's fallacy bias. We can explain
      the neural basis of this bias in terms of a biologically motivated neural model
      that learns from errors in predicting what will happen next. Through mere
      exposure to random sequences over time, the model naturally develops a
      representation that is biased toward alternation, because of its sensitivity to
      some surprisingly rich statistical structure that emerges in these random
      sequences. Furthermore, the model directly produces the best-fitting bias-gain
      parameter for an existing Bayesian model, by which we obtain an accurate fit to
      the human data in random sequence production. These results show that our
      seemingly irrational, biased view of randomness can be understood instead as the
      perfectly reasonable response of an effective learning mechanism to subtle
      statistical structure embedded in random sequences. 

PMID- 25775567
TI  - Cooperation and tensions in multiethnic corporate societies using Teotihuacan,
      Central Mexico, as a case study.
AB  - In this paper, I address the case of a corporate society in Central Mexico. After
      volcanic eruptions triggered population displacements in the southern Basin of
      Mexico during the first and fourth centuries A.D., Teotihuacan became a
      multiethnic settlement. Groups from different backgrounds settled primarily on
      the periphery of the metropolis; nevertheless, around the core, intermediate
      elites actively fostered the movement of sumptuary goods and the arrival of
      workers from diverse homelands for a range of specialized tasks. Some of these
      skilled craftsmen acquired status and perhaps economic power as a result of the
      dynamic competition among neighborhoods to display the most lavish sumptuary
      goods, as well as to manufacture specific symbols of identity that distinguished
      one neighborhood from another, such as elaborate garments and headdresses. Cotton
      attire worn by the Teotihuacan elite may have been one of the goods that granted
      economic importance to neighborhood centers such as Teopancazco, a compound that
      displayed strong ties to the Gulf Coast where cotton cloth was made. The ruling
      elite controlled raw materials that came from afar whereas the intermediate elite
      may have been more active in providing other sumptuary goods: pigments,
      cosmetics, slate, greenstone, travertine, and foreign pottery. The contrast
      between the corporate organization at the base and top of Teotihuacan society and
      the exclusionary organization of the neighborhoods headed by the highly
      competitive intermediate elite introduced tensions that set the stage for
      Teotihuacan's collapse. 

PMID- 25775566
TI  - Arrhythmogenesis in a catecholaminergic polymorphic ventricular tachycardia
      mutation that depresses ryanodine receptor function.
AB  - Current mechanisms of arrhythmogenesis in catecholaminergic polymorphic
      ventricular tachycardia (CPVT) require spontaneous Ca(2+) release via cardiac
      ryanodine receptor (RyR2) channels affected by gain-of-function mutations. Hence,
      hyperactive RyR2 channels eager to release Ca(2+) on their own appear as
      essential components of this arrhythmogenic scheme. This mechanism, therefore,
      appears inadequate to explain lethal arrhythmias in patients harboring RyR2
      channels destabilized by loss-of-function mutations. We aimed to elucidate
      arrhythmia mechanisms in a RyR2-linked CPVT mutation (RyR2-A4860G) that depresses
      channel activity. Recombinant RyR2-A4860G protein was expressed equally as wild
      type (WT) RyR2, but channel activity was dramatically inhibited, as inferred by
      [(3)H]ryanodine binding and single channel recordings. Mice heterozygous for the
      RyR2-A4860G mutation (RyR2-A4860G(+/-)) exhibited basal bradycardia but no
      cardiac structural alterations; in contrast, no homozygotes were detected at
      birth, suggesting a lethal phenotype. Sympathetic stimulation elicited malignant
      arrhythmias in RyR2-A4860G(+/-) hearts, recapitulating the phenotype originally
      described in a human patient with the same mutation. In isoproterenol-stimulated
      ventricular myocytes, the RyR2-A4860G mutation decreased the peak of Ca(2+)
      release during systole, gradually overloading the sarcoplasmic reticulum with
      Ca(2+). The resultant Ca(2+) overload then randomly caused bursts of prolonged
      Ca(2+) release, activating electrogenic Na(+)-Ca(2+) exchanger activity and
      triggering early afterdepolarizations. The RyR2-A4860G mutation reveals novel
      pathways by which RyR2 channels engage sarcolemmal currents to produce life
      threatening arrhythmias. 

PMID- 25775568
TI  - Engineered stabilization and structural analysis of the autoinhibited
      conformation of PDE4.
AB  - Phosphodiesterase 4 (PDE4) is an essential contributor to intracellular signaling
      and an important drug target. The four members of this enzyme family (PDE4A to 
      D) are functional dimers in which each subunit contains two upstream conserved
      regions (UCR), UCR1 and -2, which precede the C-terminal catalytic domain.
      Alternative promoters, transcriptional start sites, and mRNA splicing lead to the
      existence of over 25 variants of PDE4, broadly classified as long, short, and
      supershort forms. We report the X-ray crystal structure of long form PDE4B
      containing UCR1, UCR2, and the catalytic domain, crystallized as a dimer in which
      a disulfide bond cross-links cysteines engineered into UCR2 and the catalytic
      domain. Biochemical and mass spectrometric analyses showed that the UCR2
      catalytic domain interaction occurs in trans, and established that this
      interaction regulates the catalytic activity of PDE4. By elucidating the key
      structural determinants of dimerization, we show that only long forms of PDE4 can
      be regulated by this mechanism. The results also provide a structural basis for
      the long-standing observation of high- and low-affinity binding sites for the
      prototypic inhibitor rolipram. 

PMID- 25775570
TI  - HIV-1 replication capacity: Setting the pace of disease.

PMID- 25775569
TI  - Transcriptome analysis reveals transmembrane targets on transplantable midbrain
      dopamine progenitors.
AB  - An important challenge for the continued development of cell therapy for
      Parkinson's disease (PD) is the establishment of procedures that better
      standardize cell preparations for use in transplantation. Although cell sorting
      has been an anticipated strategy, its application has been limited by lack of
      knowledge regarding transmembrane proteins that can be used to target and isolate
      progenitors for midbrain dopamine (mDA) neurons. We used a "FACS-array" approach
      to identify 18 genes for transmembrane proteins with high expression in mDA
      progenitors and describe the utility of four of these targets (Alcam, Chl1,
      Gfra1, and Igsf8) for isolating mDA progenitors from rat primary ventral
      mesencephalon through flow cytometry. Alcam and Chl1 facilitated a significant
      enrichment of mDA neurons following transplantation, while targeting of Gfra1
      allowed for robust separation of dopamine and serotonin neurons. Importantly, we
      also show that mDA progenitors isolated on the basis of transmembrane proteins
      are capable of extensive, functional innervation of the host striatum and
      correction of motor impairment in a unilateral model of PD. These results are
      highly relevant for current efforts to establish safe and effective stem cell
      based procedures for PD, where clinical translation will almost certainly require
      safety and standardization measures in order to deliver well-characterized cell
      preparations. 

PMID- 25775571
TI  - Cortical computation in mammals and birds.

PMID- 25775574
TI  - Correction for Boschin et al., Essential functions of primate frontopolar cortex
      in cognition.

PMID- 25775573
TI  - Microdroplet fusion mass spectrometry for fast reaction kinetics.
AB  - We investigated the fusion of high-speed liquid droplets as a way to record the
      kinetics of liquid-phase chemical reactions on the order of microseconds. Two
      streams of micrometer-size droplets collide with one another. The droplets that
      fused (13 MUm in diameter) at the intersection of the two streams entered the
      heated capillary inlet of a mass spectrometer. The mass spectrum was recorded as
      a function of the distance x between the mass spectrometer inlet and the droplet
      fusion center. Fused droplet trajectories were imaged with a high-speed camera,
      revealing that the droplet fusion occurred approximately within a 500-MUm radius
      from the droplet fusion center and both the size and the speed of the fused
      droplets remained relatively constant as they traveled from the droplet fusion
      center to the mass spectrometer inlet. Evidence is presented that the reaction
      effectively stops upon entering the heated inlet of the mass spectrometer. Thus,
      the reaction time was proportional to x and could be measured and manipulated by
      controlling the distance x. Kinetic studies were carried out in fused water
      droplets for acid-induced unfolding of cytochrome c and hydrogen-deuterium
      exchange in bradykinin. The kinetics of the former revealed the slowing of the
      unfolding rates at the early stage of the reaction within 50 MUs. The hydrogen
      deuterium exchange revealed the existence of two distinct populations with fast
      and slow exchange rates. These studies demonstrated the power of this technique
      to detect reaction intermediates in fused liquid droplets with microsecond
      temporal resolution. 

PMID- 25775572
TI  - Transmembrane tethering of synaptotagmin to synaptic vesicles controls multiple
      modes of neurotransmitter release.
AB  - Synaptotagmin 1 (Syt1) is a synaptic vesicle integral membrane protein that
      regulates neurotransmitter release by activating fast synchronous fusion and
      suppressing slower asynchronous release. The cytoplasmic C2 domains of Syt1
      interact with SNAREs and plasma membrane phospholipids in a Ca(2+)-dependent
      manner and can substitute for full-length Syt1 in in vitro membrane fusion
      assays. To determine whether synaptic vesicle tethering of Syt1 is required for
      normal fusion in vivo, we performed a structure-function study with tethering
      mutants at the Drosophila larval neuromuscular junction. Transgenic animals
      expressing only the cytoplasmic C2 domains or full-length Syt1 tethered to the
      plasma membrane failed to restore synchronous synaptic vesicle fusion, and also
      failed to clamp spontaneous vesicle release. In addition, transgenic animals with
      shorter, but not those with longer, linker regions separating the C2 domains from
      the transmembrane segment abolished Syt1's ability to activate synchronous
      vesicle fusion. Similar defects were observed when C2 domain alignment was
      altered to C2B-C2A from the normal C2A-C2B orientation, leaving the tether itself
      intact. Although cytoplasmic and plasma membrane-tethered Syt1 variants could not
      restore synchronous release in syt1 null mutants, they were very effective in
      promoting fusion through the slower asynchronous pathway. As such, the
      subcellular localization of Syt1 within synaptic terminals is important for the
      temporal dynamics that underlie synchronous and asynchronous neurotransmitter
      release. 

PMID- 25775575
TI  - Simulation of the isotropic EXAFS spectra for the S2 and S3 structures of the
      oxygen evolving complex in photosystem II.
AB  - Most of the main features of water oxidation in photosystem II are now well
      understood, including the mechanism for O-O bond formation. For the intermediate
      S2 and S3 structures there is also nearly complete agreement between quantum
      chemical modeling and experiments. Given the present high degree of consensus for
      these structures, it is of high interest to go back to previous suggestions
      concerning what happens in the S2-S3 transition. Analyses of extended X-ray
      adsorption fine structure (EXAFS) experiments have indicated relatively large
      structural changes in this transition, with changes of distances sometimes larger
      than 0.3 A and a change of topology. In contrast, our previous density functional
      theory (DFT)(B3LYP) calculations on a cluster model showed very small changes,
      less than 0.1 A. It is here found that the DFT structures are also consistent
      with the EXAFS spectra for the S2 and S3 states within normal errors of DFT. The
      analysis suggests that there are severe problems in interpreting EXAFS spectra
      for these complicated systems. 

PMID- 25775576
TI  - Half-century evidence from western Canada shows forest dynamics are primarily
      driven by competition followed by climate.
AB  - Tree mortality, growth, and recruitment are essential components of forest
      dynamics and resiliency, for which there is great concern as climate change
      progresses at high latitudes. Tree mortality has been observed to increase over
      the past decades in many regions, but the causes of this increase are not well
      understood, and we know even less about long-term changes in growth and
      recruitment rates. Using a dataset of long-term (1958-2009) observations on 1,680
      permanent sample plots from undisturbed natural forests in western Canada, we
      found that tree demographic rates have changed markedly over the last five
      decades. We observed a widespread, significant increase in tree mortality, a
      significant decrease in tree growth, and a similar but weaker trend of decreasing
      recruitment. However, these changes varied widely across tree size, forest age,
      ecozones, and species. We found that competition was the primary factor causing
      the long-term changes in tree mortality, growth, and recruitment. Regional
      climate had a weaker yet still significant effect on tree mortality, but little
      effect on tree growth and recruitment. This finding suggests that internal
      community-level processes-more so than external climatic factors-are driving
      forest dynamics. 

PMID- 25775577
TI  - Origins of narcissism in children.
AB  - Narcissism levels have been increasing among Western youth, and contribute to
      societal problems such as aggression and violence. The origins of narcissism,
      however, are not well understood. Here, we report, to our knowledge, the first
      prospective longitudinal evidence on the origins of narcissism in children. We
      compared two perspectives: social learning theory (positing that narcissism is
      cultivated by parental overvaluation) and psychoanalytic theory (positing that
      narcissism is cultivated by lack of parental warmth). We timed the study in late
      childhood (ages 7-12), when individual differences in narcissism first emerge. In
      four 6-mo waves, 565 children and their parents reported child narcissism, child
      self-esteem, parental overvaluation, and parental warmth. Four-wave cross-lagged
      panel models were conducted. Results support social learning theory and
      contradict psychoanalytic theory: Narcissism was predicted by parental
      overvaluation, not by lack of parental warmth. Thus, children seem to acquire
      narcissism, in part, by internalizing parents' inflated views of them (e.g., "I
      am superior to others" and "I am entitled to privileges"). Attesting to the
      specificity of this finding, self-esteem was predicted by parental warmth, not by
      parental overvaluation. These findings uncover early socialization experiences
      that cultivate narcissism, and may inform interventions to curtail narcissistic
      development at an early age. 

PMID- 25775578
TI  - Stimulating minds to wander.

PMID- 25775579
TI  - Vernalizing cold is registered digitally at FLC.
AB  - A fundamental property of many organisms is an ability to sense, evaluate, and
      respond to environmental signals. In some situations, generation of an
      appropriate response requires long-term information storage. A classic example is
      vernalization, where plants quantitatively sense long-term cold and
      epigenetically store this cold-exposure information to regulate flowering time.
      In Arabidopsis thaliana, stable epigenetic memory of cold is digital: following
      long-term cold exposure, cells respond autonomously in an all-or-nothing fashion,
      with the fraction of cells that stably silence the floral repressor flowering
      locus C (FLC) increasing with the cold exposure duration. However, during cold
      exposure itself it is unknown whether vernalizing cold is registered at FLC in
      individual cells in an all-or-nothing (digital) manner or is continuously varying
      (analog). Using mathematical modeling, we found that analog registration of cold
      temperature is problematic due to impaired analog-to-digital conversion into
      stable memory. This disadvantage is particularly acute when responding to short
      cold periods, but is absent when cold temperatures are registered digitally at
      FLC. We tested this prediction experimentally, exposing plants to short periods
      of cold interrupted with even shorter warm breaks. For FLC expression, we found
      that the system responds similarly to both interrupted and uninterrupted cold,
      arguing for a digital mechanism integrating long-term temperature exposure.

PMID- 25775581
TI  - QnAs with Burton Richter.

PMID- 25775580
TI  - The CDX1-microRNA-215 axis regulates colorectal cancer stem cell differentiation.
AB  - The transcription factor caudal-type homeobox 1 (CDX1) is a key regulator of
      differentiation in the normal colon and in colorectal cancer (CRC). CDX1
      activates the expression of enterocyte genes, but it is not clear how the
      concomitant silencing of stem cell genes is achieved. MicroRNAs (miRNAs) are
      important mediators of gene repression and have been implicated in tumor
      suppression and carcinogenesis, but the roles of miRNAs in differentiation,
      particularly in CRC, remain poorly understood. Here, we identified microRNA-215
      (miR-215) as a direct transcriptional target of CDX1 by using high-throughput
      small RNA sequencing to profile miRNA expression in two pairs of CRC cell lines:
      CDX1-low HCT116 and HCT116 with stable CDX1 overexpression, and CDX1-high LS174T
      and LS174T with stable CDX1 knockdown. Validation of candidate miRNAs identified
      by RNA-seq in a larger cell-line panel revealed miR-215 to be most significantly
      correlated with CDX1 expression. Quantitative ChIP-PCR and promoter luciferase
      assays confirmed that CDX1 directly activates miR-215 transcription. miR-215
      expression is depleted in FACS-enriched cancer stem cells compared with unsorted
      samples. Overexpression of miR-215 in poorly differentiated cell lines causes a
      decrease in clonogenicity, whereas miR-215 knockdown increases clonogenicity and
      impairs differentiation in CDX1-high cell lines. We identified the genome-wide
      targets of miR-215 and found that miR-215 mediates the repression of cell cycle
      and stemness genes downstream of CDX1. In particular, the miR-215 target gene
      BMI1 has been shown to promote stemness and self-renewal and to vary inversely
      with CDX1. Our work situates miR-215 as a link between CDX1 expression and BMI1
      repression that governs differentiation in CRC. 

PMID- 25775582
TI  - Immunomodulatory spherical nucleic acids.
AB  - Immunomodulatory nucleic acids have extraordinary promise for treating disease,
      yet clinical progress has been limited by a lack of tools to safely increase
      activity in patients. Immunomodulatory nucleic acids act by agonizing or
      antagonizing endosomal toll-like receptors (TLR3, TLR7/8, and TLR9), proteins
      involved in innate immune signaling. Immunomodulatory spherical nucleic acids
      (SNAs) that stimulate (immunostimulatory, IS-SNA) or regulate (immunoregulatory,
      IR-SNA) immunity by engaging TLRs have been designed, synthesized, and
      characterized. Compared with free oligonucleotides, IS-SNAs exhibit up to 80-fold
      increases in potency, 700-fold higher antibody titers, 400-fold higher cellular
      responses to a model antigen, and improved treatment of mice with lymphomas. IR
      SNAs exhibit up to eightfold increases in potency and 30% greater reduction in
      fibrosis score in mice with nonalcoholic steatohepatitis (NASH). Given the
      clinical potential of SNAs due to their potency, defined chemical nature, and
      good tolerability, SNAs are attractive new modalities for developing
      immunotherapies. 

PMID- 25775583
TI  - Microbial community transcriptional networks are conserved in three domains at
      ocean basin scales.
AB  - Planktonic microbial communities in the ocean are typically dominated by several
      cosmopolitan clades of Bacteria, Archaea, and Eukarya characterized by their
      ribosomal RNA gene phylogenies and genomic features. Although the environments
      these communities inhabit range from coastal to open ocean waters, how the
      biological dynamics vary between such disparate habitats is not well known. To
      gain insight into the differential activities of microbial populations inhabiting
      different oceanic provinces we compared the daily metatranscriptome profiles of
      related microbial populations inhabiting surface waters of both a coastal
      California upwelling region (CC) as well as the oligotrophic North Pacific
      Subtropical Gyre (NPSG). Transcriptional networks revealed that the dominant
      photoautotrophic microbes in each environment (Ostreococcus in CC,
      Prochlorococcus in NPSG) were central determinants of overall community
      transcriptome dynamics. Furthermore, heterotrophic bacterial clades common to
      both ecosystems (SAR11, SAR116, SAR86, SAR406, and Roseobacter) displayed
      conserved, genome-wide inter- and intrataxon transcriptional patterns and diel
      cycles. Populations of SAR11 and SAR86 clades in particular exhibited tightly
      coordinated transcriptional patterns in both coastal and pelagic ecosystems,
      suggesting that specific biological interactions between these groups are
      widespread in nature. Our results identify common diurnally oscillating behaviors
      among diverse planktonic microbial species regardless of habitat, suggesting that
      highly conserved temporally phased biotic interactions are ubiquitous among
      planktonic microbial communities worldwide. 

PMID- 25775584
TI  - Theories of ethnicity and the dynamics of ethnic change in multiethnic societies.
AB  - I modify Fredrik Barth's approach, which sees ethnic group building as a
      signaling system, to place it within a framework that draws from collective
      action and costly signaling theories. From these perspectives, ethnic signaling,
      although representing a costly penalty to group members, is one effective form of
      communication that facilitates collective management of resources. I then
      identify three contexts in which the benefits of ethnic group building are likely
      to outweigh its signaling costs: in politically chaotic refuge and periphery
      zones; in the context of long-distance specialist trading groups; and within the
      territorial scope of failed states. I point to selected data from the Mughal and
      Aztec polities to illustrate how a combination of effective public goods
      management, in highly collective states, and the growth of highly integrated
      commercial economies will render ethnic group building superfluous. 

PMID- 25775585
TI  - Coselected genes determine adaptive variation in herbivore resistance throughout
      the native range of Arabidopsis thaliana.
AB  - The "mustard oil bomb" is a major defense mechanism in the Brassicaceae, which
      includes crops such as canola and the model plant Arabidopsis thaliana. These
      plants produce and store blends of amino acid-derived secondary metabolites
      called glucosinolates. Upon tissue rupture by natural enemies, the myrosinase
      enzyme hydrolyses glucosinolates, releasing defense molecules. Brassicaceae
      display extensive variation in the mixture of glucosinolates that they produce.
      To investigate the genetics underlying natural variation in glucosinolate
      profiles, we conducted a large genome-wide association study of 22 methionine
      derived glucosinolates using A. thaliana accessions from across Europe. We found
      that 36% of among accession variation in overall glucosinolate profile was
      explained by genetic differentiation at only three known loci from the
      glucosinolate pathway. Glucosinolate-related SNPs were up to 490-fold enriched in
      the extreme tail of the genome-wide [Formula: see text] scan, indicating strong
      selection on loci controlling this pathway. Glucosinolate profiles displayed a
      striking longitudinal gradient with alkenyl and hydroxyalkenyl glucosinolates
      enriched in the West. We detected a significant contribution of glucosinolate
      loci toward general herbivore resistance and lifetime fitness in common garden
      experiments conducted in France, where accessions are enriched in
      hydroxyalkenyls. In addition to demonstrating the adaptive value of glucosinolate
      profile variation, we also detected long-distance linkage disequilibrium at two
      underlying loci, GS-OH and GS-ELONG. Locally cooccurring alleles at these loci
      display epistatic effects on herbivore resistance and fitness in ecologically
      realistic conditions. Together, our results suggest that natural selection has
      favored a locally adaptive configuration of physically unlinked loci in Western
      Europe. 

PMID- 25775586
TI  - A 17-My-old whale constrains onset of uplift and climate change in east Africa.
AB  - Timing and magnitude of surface uplift are key to understanding the impact of
      crustal deformation and topographic growth on atmospheric circulation,
      environmental conditions, and surface processes. Uplift of the East African
      Plateau is linked to mantle processes, but paleoaltimetry data are too scarce to
      constrain plateau evolution and subsequent vertical motions associated with
      rifting. Here, we assess the paleotopographic implications of a beaked whale
      fossil (Ziphiidae) from the Turkana region of Kenya found 740 km inland from the
      present-day coastline of the Indian Ocean at an elevation of 620 m. The specimen
      is ~ 17 My old and represents the oldest derived beaked whale known, consistent
      with molecular estimates of the emergence of modern strap-toothed whales
      (Mesoplodon). The whale traveled from the Indian Ocean inland along an eastward
      directed drainage system controlled by the Cretaceous Anza Graben and was
      stranded slightly above sea level. Surface uplift from near sea level coincides
      with paleoclimatic change from a humid environment to highly variable and much
      drier conditions, which altered biotic communities and drove evolution in east
      Africa, including that of primates.

PMID- 25775587
TI  - Two transcription factors, Pou4f2 and Isl1, are sufficient to specify the retinal
      ganglion cell fate.
AB  - As with other retinal cell types, retinal ganglion cells (RGCs) arise from
      multipotent retinal progenitor cells (RPCs), and their formation is regulated by
      a hierarchical gene-regulatory network (GRN). Within this GRN, three
      transcription factors--atonal homolog 7 (Atoh7), POU domain, class 4,
      transcription factor 2 (Pou4f2), and insulin gene enhancer protein 1 (Isl1)-
      occupy key node positions at two different stages of RGC development. Atoh7 is
      upstream and is required for RPCs to gain competence for an RGC fate, whereas
      Pou4f2 and Isl1 are downstream and regulate RGC differentiation. However, the
      genetic and molecular basis for the specification of the RGC fate, a key step in
      RGC development, remains unclear. Here we report that ectopic expression of
      Pou4f2 and Isl1 in the Atoh7-null retina using a binary knockin-transgenic system
      is sufficient for the specification of the RGC fate. The RGCs thus formed are
      largely normal in gene expression, survive to postnatal stages, and are
      physiologically functional. Our results indicate that Pou4f2 and Isl1 compose a
      minimally sufficient regulatory core for the RGC fate. We further conclude that
      during development a core group of limited transcription factors, including
      Pou4f2 and Isl1, function downstream of Atoh7 to determine the RGC fate and
      initiate RGC differentiation.

PMID- 25775588
TI  - Cortical network models of impulse firing in the resting and active states
      predict cortical energetics.
AB  - Measurements of the cortical metabolic rate of glucose oxidation [CMR(glc(ox))]
      have provided a number of interesting and, in some cases, surprising
      observations. One is the decline in CMR(glc(ox)) during anesthesia and non-rapid
      eye movement (NREM) sleep, and another, the inverse relationship between the
      resting-state CMR(glc(ox)) and the transient following input from the thalamus.
      The recent establishment of a quantitative relationship between synaptic and
      action potential activity on the one hand and CMR(glc(ox)) on the other allows
      neural network models of such activity to probe for possible mechanistic
      explanations of these phenomena. We have carried out such investigations using
      cortical models consisting of networks of modules with excitatory and inhibitory
      neurons, each receiving excitatory inputs from outside the network in addition to
      intermodular connections. Modules may be taken as regions of cortical interest,
      the inputs from outside the network as arising from the thalamus, and the
      intermodular connections as long associational fibers. The model shows that the
      impulse frequency of different modules can differ from each other by less than
      10%, consistent with the relatively uniform CMR(glc(ox)) observed across
      different regions of cortex. The model also shows that, if correlations of the
      average impulse rate between different modules decreases, there is a concomitant
      decrease in the average impulse rate in the modules, consistent with the observed
      drop in CMR(glc(ox)) in NREM sleep and under anesthesia. The model also explains
      why a transient thalamic input to sensory cortex gives rise to responses with
      amplitudes inversely dependent on the resting-state frequency, and therefore
      resting-state CMR(glc(ox)).

PMID- 25775589
TI  - Arabidopsis DET1 degrades HFR1 but stabilizes PIF1 to precisely regulate seed
      germination.
AB  - Seed is an essential propagation organ and a critical strategy adopted by
      terrestrial flowering plants to colonize the land. The ability of seeds to
      accurately respond to light is vital for plant survival. However, the underlying
      mechanism is largely unknown. In this study, we reveal a circuit of triple feed
      forward loops adopted by Arabidopsis seeds to exclusively repress germination in
      dark conditions and precisely initiate germination under diverse light
      conditions. We identify that de-etiolated 1 (DET1), an evolutionarily conserved
      protein, is a central repressor of light-induced seed germination. Genetic
      analysis demonstrates that DET1 functions upstream of long hypocotyl in far-red 1
      (HFR1) and phytochrome interacting factor 1 (PIF1), the key positive and negative
      transcription regulators in seed germination. We further find that DET1 and
      constitutive photomorphogenic 10 (COP10) target HFR1 for protein degradation by
      assembling a COP10-DET1-damaged DNA binding protein 1-cullin4 E3 ligase complex.
      Moreover, DET1 and COP10 directly interact with and promote the protein stability
      of PIF1. Computational modeling reveals that phytochrome B (phyB)-DET1-HFR1-PIF1
      and phyB-DET1-Protease-PIF1 are new signaling pathways, independent of the
      previously identified phyB-PIF1 pathway, respectively mediating the rapid and
      time-lapse responses to light irradiation. The model-simulated results are highly
      consistent with their experimental validations, suggesting that our mathematical
      model captures the essence of Arabidopsis seed germination networks. Taken
      together, this study provides a comprehensive molecular framework for light
      regulated seed germination, improving our understanding of how plants respond to
      changeable environments. 

PMID- 25775590
TI  - Mitochondrial metabolism is regulated by thioredoxin.

PMID- 25775591
TI  - Thermostable ricin vaccine protects rhesus macaques against aerosolized ricin:
      Epitope-specific neutralizing antibodies correlate with protection.
AB  - Ricin toxin (RT) is the second most lethal toxin known; it has been designated by
      the CDC as a select agent. RT is made by the castor bean plant; an estimated
      50,000 tons of RT are produced annually as a by-product of castor oil. RT has two
      subunits, a ribotoxic A chain (RTA) and galactose-binding B chain (RTB). RT binds
      to all mammalian cells and once internalized, a single RTA catalytically
      inactivates all of the ribosomes in a cell. Administered as an aerosol, RT causes
      rapid lung damage and fibrosis followed by death. There are no Food and Drug
      Administration-approved vaccines and treatments are only effective in the first
      few hours after exposure. We have developed a recombinant RTA vaccine that has
      two mutations V76M/Y80A (RiVax). The protein is expressed in Escherichia coli and
      is nontoxic and immunogenic in mice, rabbits, and humans. When vaccinated mice
      are challenged with injected, aerosolized, or orally administered (gavaged) RT,
      they are completely protected. We have now developed a thermostable, aluminum
      adjuvant-containing formulation of RiVax and tested it in rhesus macaques. After
      three injections, the animals developed antibodies that completely protected them
      from a lethal dose of aerosolized RT. These antibodies neutralized RT and
      competed to varying degrees with a panel of neutralizing and nonneutralizing
      mouse monoclonal antibodies known to recognize specific epitopes on native RTA.
      The resulting antibody competition profile could represent an immunologic
      signature of protection. Importantly, the same signature was observed using sera
      from RiVax-immunized humans. 

PMID- 25775592
TI  - Human Ebola virus infection results in substantial immune activation.
AB  - Four Ebola patients received care at Emory University Hospital, presenting a
      unique opportunity to examine the cellular immune responses during acute Ebola
      virus infection. We found striking activation of both B and T cells in all four
      patients. Plasmablast frequencies were 10-50% of B cells, compared with less than
      1% in healthy individuals. Many of these proliferating plasmablasts were IgG
      positive, and this finding coincided with the presence of Ebola virus-specific
      IgG in the serum. Activated CD4 T cells ranged from 5 to 30%, compared with 1-2%
      in healthy controls. The most pronounced responses were seen in CD8 T cells, with
      over 50% of the CD8 T cells expressing markers of activation and proliferation.
      Taken together, these results suggest that all four patients developed robust
      immune responses during the acute phase of Ebola virus infection, a finding that
      would not have been predicted based on our current assumptions about the highly
      immunosuppressive nature of Ebola virus. Also, quite surprisingly, we found
      sustained immune activation after the virus was cleared from the plasma, observed
      most strikingly in the persistence of activated CD8 T cells, even 1 mo after the
      patients' discharge from the hospital. These results suggest continued antigen
      stimulation after resolution of the disease. From these convalescent time points,
      we identified CD4 and CD8 T-cell responses to several Ebola virus proteins, most
      notably the viral nucleoprotein. Knowledge of the viral proteins targeted by T
      cells during natural infection should be useful in designing vaccines against
      Ebola virus. 

PMID- 25775593
TI  - Identification of FOXO targets that generate diverse features of the diapause
      phenotype in the mosquito Culex pipiens.
AB  - Insulin and juvenile hormone signaling direct entry of the mosquito Culex pipiens
      into its overwintering adult diapause, and these two critical signaling pathways
      appear to do so by converging on the regulation of forkhead transcription factor
      (FOXO). Diapause is a complex phenotype, and FOXO emerges as a prime candidate
      for activating many of the diverse physiological pathways that generate the
      diapause phenotype. Here, we used ChIP sequencing to identify direct targets of
      FOXO. The nearest gene in a 10-kb region surrounding a predicted binding site was
      extracted for each binding site, resulting in a dataset containing genes
      potentially regulated by FOXO. By selecting candidate genes based on their
      functional relevance to diapause, we identified five gene categories of potential
      interest, including stress tolerance, metabolic pathways, lifespan extension,
      cell cycle and growth regulation, and circadian rhythms. Twelve targets were
      prioritized for further analysis, 10 of which were validated by ChIP-quantitative
      PCR and quantitative real-time PCR. These 10 genes activated by FOXO are highly
      up-regulated during diapause and are thus strong candidates for implementation of
      the diapause syndrome. 

PMID- 25775594
TI  - Surface biosignatures of exo-earths: remote detection of extraterrestrial life.
AB  - Exoplanet discovery has made remarkable progress, with the first rocky planets
      having been detected in the central star's liquid water habitable zone. The
      remote sensing techniques used to characterize such planets for potential
      habitability and life rely solely on our understanding of life on Earth. The
      vegetation red edge from terrestrial land plants is often used as a direct
      signature of life, but it occupies only a small niche in the environmental
      parameter space that binds life on present-day Earth and has been widespread for
      only about 460 My. To more fully exploit the diversity of the one example of life
      known, we measured the spectral characteristics of 137 microorganisms containing
      a range of pigments, including ones isolated from Earth's most extreme
      environments. Our database covers the visible and near-infrared to the short
      wavelength infrared (0.35-2.5 um) portions of the electromagnetic spectrum and is
      made freely available from biosignatures.astro.cornell.edu. Our results show how
      the reflectance properties are dominated by the absorption of light by pigments
      in the visible portion and by strong absorptions by the cellular water of
      hydration in the infrared (up to 2.5 um) portion of the spectrum. Our spectral
      library provides a broader and more realistic guide based on Earth life for the
      search for surface features of extraterrestrial life. The library, when used as
      inputs for modeling disk-integrated spectra of exoplanets, in preparation for the
      next generation of space- and ground-based instruments, will increase the chances
      of detecting life. 

PMID- 25775595
TI  - Recombination in diverse maize is stable, predictable, and associated with
      genetic load.
AB  - Among the fundamental evolutionary forces, recombination arguably has the largest
      impact on the practical work of plant breeders. Varying over 1,000-fold across
      the maize genome, the local meiotic recombination rate limits the resolving power
      of quantitative trait mapping and the precision of favorable allele
      introgression. The consequences of low recombination also theoretically extend to
      the species-wide scale by decreasing the power of selection relative to genetic
      drift, and thereby hindering the purging of deleterious mutations. In this study,
      we used genotyping-by-sequencing (GBS) to identify 136,000 recombination
      breakpoints at high resolution within US and Chinese maize nested association
      mapping populations. We find that the pattern of cross-overs is highly
      predictable on the broad scale, following the distribution of gene density and
      CpG methylation. Several large inversions also suppress recombination in distinct
      regions of several families. We also identify recombination hotspots ranging in
      size from 1 kb to 30 kb. We find these hotspots to be historically stable and,
      compared with similar regions with low recombination, to have strongly
      differentiated patterns of DNA methylation and GC content. We also provide
      evidence for the historical action of GC-biased gene conversion in recombination
      hotspots. Finally, using genomic evolutionary rate profiling (GERP) to identify
      putative deleterious polymorphisms, we find evidence for reduced genetic load in
      hotspot regions, a phenomenon that may have considerable practical importance for
      breeding programs worldwide. 

PMID- 25775596
TI  - Reprogramming of Sertoli cells to fetal-like Leydig cells by Wt1 ablation.
AB  - Sertoli and Leydig cells, the two major somatic cell types in the testis, have
      different morphologies and functions. Both are essential for gonad development
      and spermatogenesis. However, whether these cells are derived from the same
      progenitor cells and the mechanism regulating the differentiation between these
      two cell types during gonad development remains unclear. A previous study showed
      that overactivation of Ctnnb1 (cadherin-associated protein, beta 1) in Sertoli
      cells resulted in Sertoli cell tumors. Surprisingly, in the present study, we
      found that simultaneous deletion of Wilms' Tumor Gene 1 (Wt1) and overactivation
      of Ctnnb1 in Sertoli cells led to Leydig cell-like tumor development. Lineage
      tracing experiments revealed that the Leydig-like tumor cells were derived from
      Sertoli cells. Further studies confirmed that Wt1 is required for the maintenance
      of the Sertoli cell lineage and that deletion of Wt1 resulted in the
      reprogramming of Sertoli cells to Leydig cells. Consistent with this
      interpretation, overexpression of Wt1 in Leydig cells led to the up-regulation of
      Sertoli cell-specific gene expression and the down-regulation of steroidogenic
      gene expression. These results demonstrate that the distinction between Sertoli
      cells and Leydig cells is regulated by Wt1, implying that these two cell types
      most likely originate from the same progenitor cells. This study thus provides a
      novel concept for somatic cell fate determination in testis development that may
      also represent an etiology of male infertility in human patients. 

PMID- 25775597
TI  - Regional inactivations of primate ventral prefrontal cortex reveal two distinct
      mechanisms underlying negative bias in decision making.
AB  - Dysregulation of the orbitofrontal and ventrolateral prefrontal cortices is
      implicated in anxiety and mood disorders, but the specific contributions of each
      region are unknown, including how they gate the impact of threat on decision
      making. To address this, the effects of GABAergic inactivation of these regions
      were studied in marmoset monkeys performing an instrumental approach-avoidance
      decision-making task that is sensitive to changes in anxiety. Inactivation of
      either region induced a negative bias away from punishment that could be
      ameliorated with anxiolytic treatment. However, whereas the effects of
      ventrolateral prefrontal cortex inactivation on punishment avoidance were seen
      immediately, those of orbitofrontal cortex inactivation were delayed and their
      expression was dependent upon an amygdala-anterior hippocampal circuit. We
      propose that these negative biases result from deficits in attentional control
      and punishment prediction, respectively, and that they provide the basis for
      understanding how distinct regional prefrontal dysregulation contributes to the
      heterogeneity of anxiety disorders with implications for cognitive-behavioral
      treatment strategies. 

PMID- 25775598
TI  - Adult hippocampal neural stem and progenitor cells regulate the neurogenic niche
      by secreting VEGF.
AB  - The adult hippocampus hosts a population of neural stem and progenitor cells
      (NSPCs) that proliferates throughout the mammalian life span. To date, the new
      neurons derived from NSPCs have been the primary measure of their functional
      relevance. However, recent studies show that undifferentiated cells may shape
      their environment through secreted growth factors. Whether endogenous adult NSPCs
      secrete functionally relevant growth factors remains unclear. We show that adult
      hippocampal NSPCs secrete surprisingly large quantities of the essential growth
      factor VEGF in vitro and in vivo. This self-derived VEGF is functionally relevant
      for maintaining the neurogenic niche as inducible, NSPC-specific loss of VEGF
      results in impaired stem cell maintenance despite the presence of VEGF produced
      from other niche cell types. These findings reveal adult hippocampal NSPCs as an
      unanticipated source of an essential growth factor and imply an exciting
      functional role for adult brain NSPCs as secretory cells. 

PMID- 25775599
TI  - ORMDL orosomucoid-like proteins are degraded by free-cholesterol-loading-induced
      autophagy.
AB  - Eukaryotic cells have evolved robust mechanisms to counter excess cholesterol
      including redistribution of lipids into different compartments and compensatory
      up-regulation of phospholipid biosynthesis. We demonstrate here that excess
      cellular cholesterol increased the activity of the endoplasmic reticulum (ER)
      enzyme serine palmitoyl-CoA transferase (SPT), the rate-limiting enzyme in
      sphingomyelin synthesis. This increased SPT activity was not due to altered
      levels of SPTLC1 or SPTLC2, the major subunits of SPT. Instead, cholesterol
      loading decreased the levels of ORMDL1, a negative regulator of SPT activity, due
      to its increased turnover. Several lines of evidence demonstrated that free
      cholesterol-induced autophagy, which led to increased turnover of ORMDL1.
      Cholesterol loading induced ORMDL1 redistribution from the ER to cytoplasmic p62
      positive autophagosomes. Coimmunoprecipitation analysis of cholesterol-loaded
      cells showed increased association between ORMDL1 and p62. The lysosomal
      inhibitor chloroquine or siRNA knockdown of Atg7 inhibited ORMDL1 degradation by
      cholesterol, whereas proteasome inhibitors showed no effect. ORMDL1 degradation
      was specific to free-cholesterol loading as autophagy induced by serum starvation
      or general ER stress did not lead to ORMDL1 degradation. ORMDL proteins are thus
      previously unidentified responders to excess cholesterol, exiting the ER to
      activate SPT and increase sphingomyelin biosynthesis, which may buffer excess
      cellular cholesterol. 

PMID- 25775600
TI  - Reduced fitness in progeny from old parents in a natural population.
AB  - A nongenetic, transgenerational effect of parental age on offspring fitness has
      been described in many taxa in the laboratory. Such a transgenerational fitness
      effect will have important influences on population dynamics, population age
      structure, and the evolution of aging and lifespan. However, effects of parental
      age on offspring lifetime fitness have never been demonstrated in a natural
      population. We show that parental age has sex-specific negative effects on
      lifetime fitness, using data from a pedigreed insular population of wild house
      sparrows. Birds whose parents were older produced fewer recruits annually than
      birds with younger parents, and the reduced number of recruits translated into a
      lifetime fitness difference. Using a long-term cross-fostering experiment, we
      demonstrate that this parental age effect is unlikely to be the result of changes
      in the environment but that it potentially is epigenetically inherited. Our study
      reveals the hidden consequences of late-life reproduction that persist into the
      next generation. 

PMID- 25775601
TI  - Sponge grade body fossil with cellular resolution dating 60 Myr before the
      Cambrian.
AB  - An extraordinarily well preserved, 600-million-year (Myr)-old, three
      dimensionally phosphatized fossil displaying multiple independent characters of
      modern adult sponges has been analyzed by SEM and synchrotron X-ray tomography.
      The fossilized animal (Eocyathispongia qiania gen. et sp. nov.) is slightly more
      than 1.2 mm wide and 1.1 mm tall, is composed of hundreds of thousands of cells,
      and has a gross structure consisting of three adjacent hollow tubes sharing a
      common base. The main tube is crowned with a large open funnel, and the others
      end in osculum-like openings to the exterior. The external surface is densely
      covered with flat tile-like cells closely resembling sponge pinacocytes, and this
      layer is punctuated with smaller pores. A dense patch of external structures that
      display the form of a lawn of sponge papillae has also survived. Within the main
      funnel, an area where features of the inner surface are preserved displays a
      regular pattern of uniform pits. Many of them are surrounded individually by
      distinct collars, mounted in a supporting reticulum. The possibility cannot be
      excluded that these pits are the remains of a field of choanocytes. The character
      set evinced by this specimen, ranging from general anatomy to cell type, uniquely
      indicates that this specimen is a fossil of probable poriferan affinity. So far,
      we have only this single specimen, and although its organized and complex
      cellular structure precludes any reasonable interpretation that its origin is
      abiogenic, confirmation that it is indeed a fossilized sponge will clearly
      require discovery of additional specimens. 

PMID- 25775603
TI  - Permafrost carbon-climate feedback is sensitive to deep soil carbon
      decomposability but not deep soil nitrogen dynamics.
AB  - Permafrost soils contain enormous amounts of organic carbon whose stability is
      contingent on remaining frozen. With future warming, these soils may release
      carbon to the atmosphere and act as a positive feedback to climate change.
      Significant uncertainty remains on the postthaw carbon dynamics of permafrost
      affected ecosystems, in particular since most of the carbon resides at depth
      where decomposition dynamics may differ from surface soils, and since nitrogen
      mineralized by decomposition may enhance plant growth. Here we show, using a
      carbon-nitrogen model that includes permafrost processes forced in an unmitigated
      warming scenario, that the future carbon balance of the permafrost region is
      highly sensitive to the decomposability of deeper carbon, with the net balance
      ranging from 21 Pg C to 164 Pg C losses by 2300. Increased soil nitrogen
      mineralization reduces nutrient limitations, but the impact of deep nitrogen on
      the carbon budget is small due to enhanced nitrogen availability from warming
      surface soils and seasonal asynchrony between deeper nitrogen availability and
      plant nitrogen demands. Although nitrogen dynamics are highly uncertain, the
      future carbon balance of this region is projected to hinge more on the rate and
      extent of permafrost thaw and soil decomposition than on enhanced nitrogen
      availability for vegetation growth resulting from permafrost thaw. 

PMID- 25775602
TI  - Universal pathway for posttransfer editing reactions: insights from the crystal
      structure of TtPheRS with puromycin.
AB  - At the amino acid binding and recognition step, phenylalanyl-tRNA synthetase
      (PheRS) faces the challenge of discrimination between cognate phenylalanine and
      closely similar noncognate tyrosine. Resampling of Tyr-tRNA(Phe) to PheRS
      increasing the number of correctly charged tRNA molecules has recently been
      revealed. Thus, the very same editing site of PheRS promotes hydrolysis of
      misacylated tRNA species, associated both with cis- and trans-editing pathways.
      Here we report the crystal structure of Thermus thermophilus PheRS (TtPheRS) at
      2.6 A resolution, in complex with phenylalanine and antibiotic puromycin
      mimicking the A76 of tRNA acylated with tyrosine. Starting from the complex
      structure and using a hybrid quantum mechanics/molecular mechanics approach, we
      investigate the pathways of editing reaction catalyzed by TtPheRS. We show that
      both 2' and 3' isomeric esters undergo mutual transformation via the cyclic
      intermediate orthoester, and the editing site can readily accommodate a model of
      Tyr-tRNA(Phe) where deacylation occurs from either the 2'- or 3'-OH. The
      suggested pathway of the hydrolytic reaction at the editing site of PheRS is of
      sufficient generality to warrant comparison with other class I and class II
      aminoacyl-tRNA synthetases. 

PMID- 25775604
TI  - Biasing moral decisions by exploiting the dynamics of eye gaze.
AB  - Eye gaze is a window onto cognitive processing in tasks such as spatial memory,
      linguistic processing, and decision making. We present evidence that information
      derived from eye gaze can be used to change the course of individuals' decisions,
      even when they are reasoning about high-level, moral issues. Previous studies
      have shown that when an experimenter actively controls what an individual sees
      the experimenter can affect simple decisions with alternatives of almost equal
      valence. Here we show that if an experimenter passively knows when individuals
      move their eyes the experimenter can change complex moral decisions. This causal
      effect is achieved by simply adjusting the timing of the decisions. We monitored
      participants' eye movements during a two-alternative forced-choice task with
      moral questions. One option was randomly predetermined as a target. At the moment
      participants had fixated the target option for a set amount of time we terminated
      their deliberation and prompted them to choose between the two alternatives.
      Although participants were unaware of this gaze-contingent manipulation, their
      choices were systematically biased toward the target option. We conclude that
      even abstract moral cognition is partly constituted by interactions with the
      immediate environment and is likely supported by gaze-dependent decision
      processes. By tracking the interplay between individuals, their sensorimotor
      systems, and the environment, we can influence the outcome of a decision without
      directly manipulating the content of the information available to them. 

PMID- 25775605
TI  - Orbital forcing of climate 1.4 billion years ago.
AB  - Fluctuating climate is a hallmark of Earth. As one transcends deep into Earth
      time, however, both the evidence for and the causes of climate change become
      difficult to establish. We report geochemical and sedimentological evidence for
      repeated, short-term climate fluctuations from the exceptionally well-preserved
      ~1.4-billion-year-old Xiamaling Formation of the North China Craton. We observe
      two patterns of climate fluctuations: On long time scales, over what amounts to
      tens of millions of years, sediments of the Xiamaling Formation record changes in
      geochemistry consistent with long-term changes in the location of the Xiamaling
      relative to the position of the Intertropical Convergence Zone. On shorter time
      scales, and within a precisely calibrated stratigraphic framework, cyclicity in
      sediment geochemical dynamics is consistent with orbital control. In particular,
      sediment geochemical fluctuations reflect what appear to be orbitally forced
      changes in wind patterns and ocean circulation as they influenced rates of
      organic carbon flux, trace metal accumulation, and the source of detrital
      particles to the sediment. 

PMID- 25775606
TI  - Facilitation of fear extinction by novelty depends on dopamine acting on D1
      subtype dopamine receptors in hippocampus.
AB  - Extinction is the learned inhibition of retrieval. Recently it was shown that a
      brief exposure to a novel environment enhances the extinction of contextual fear
      in rats, an effect explainable by a synaptic tagging-and-capture process. Here we
      examine whether this also happens with the extinction of another fear-motivated
      task, inhibitory avoidance (IA), and whether it depends on dopamine acting on D1
      or D5 receptors. Rats were trained first in IA and then in extinction of this
      task. The retention of extinction was measured 24 h later. A 5-min exposure to a
      novel environment 30 min before extinction training enhanced its retention. Right
      after exposure to the novelty, animals were given bilateral intrahippocampal
      infusions of vehicle (VEH), of the protein synthesis inhibitor anisomycin, of the
      D1/D5 dopaminergic antagonist SCH23390, of the PKA inhibitor Rp-cAMP or of the
      PKC inhibitor Go6976, and of the PKA stimulator Sp-cAMP or of the PKC stimulator
      PMA. The novelty increased hippocampal dopamine levels and facilitated the
      extinction, which was inhibited by intrahippocampal protein synthesis inhibitor
      anisomysin, D1/D5 dopaminerdic antagonist SCH23390, or PKA inhibitor Rp-cAMP and
      unaffected by PKC inhibitor Go6976; additionally, the hippocampal infusion of PKA
      stimulator Sp-cAMP reverts the effect of D1/D5 dopaminergic antagonist SCH 23390,
      but the infusion of PKC stimulator PMA does not. The results attest to the
      generality of the novelty effect on fear extinction, suggest that it relies on
      synaptic tagging and capture, and show that it depends on hippocampal dopamine D1
      but not D5 receptors. 

PMID- 25775607
TI  - Dysfunctional conformational dynamics of protein kinase A induced by a lethal
      mutant of phospholamban hinder phosphorylation.
AB  - The dynamic interplay between kinases and substrates is crucial for the formation
      of catalytically committed complexes that enable phosphoryl transfer. However, a
      clear understanding on how substrates modulate kinase structural dynamics to
      control catalytic efficiency is still missing. Here, we used solution NMR
      spectroscopy to study the conformational dynamics of two complexes of the
      catalytic subunit of the cAMP-dependent protein kinase A with WT and R14 deletion
      phospholamban, a lethal human mutant linked to familial dilated cardiomyopathy.
      Phospholamban is a central regulator of heart muscle contractility, and its
      phosphorylation by protein kinase A constitutes a primary response to beta
      adrenergic stimulation. We found that the single deletion of arginine in
      phospholamban's recognition sequence for the kinase reduces its binding affinity
      and dramatically reduces phosphorylation kinetics. Structurally, the mutant
      prevents the enzyme from adopting conformations and motions committed for
      catalysis, with concomitant reduction in catalytic efficiency. Overall, these
      results underscore the importance of a well-tuned structural and dynamic
      interplay between the kinase and its substrates to achieve physiological
      phosphorylation levels for proper Ca(2+) signaling and normal cardiac function. 

PMID- 25775609
TI  - Reasons for Treatment Changes in Patients With Moderate to Severe Psoriasis.
AB  - BACKGROUND: Psoriasis treatment involves multiple treatment arms. Treatment
      choice depends on many factors and may change, due to the chronicity of
      psoriasis. OBJECTIVE: The purpose of our study is to explore reasons for
      treatment changes in patients with moderate to severe psoriasis. METHODS: Ten
      charts of patients with moderate to severe psoriasis were reviewed. The
      medication changes and reasons for change were extracted. A "treatment change"
      was defined as switching between medication classes, adding or removing a
      medication class, or switching medications within the oral or biologic medication
      class. RESULTS: Seventy-seven treatment changes were identified. On average, 1
      treatment change occurred per year of follow-up. The most common reason for
      treatment change was inadequate disease control. CONCLUSIONS: Inadequate disease
      control with current therapy is the most common reason a physician changes
      treatment for moderate to severe psoriasis. More efficacious treatments or ways
      to improve efficacy may help improve the long-term outcomes of psoriasis.

PMID- 25775608
TI  - Silencing of end-joining repair for efficient site-specific gene insertion after
      TALEN/CRISPR mutagenesis in Aedes aegypti.
AB  - Conventional control strategies for mosquito-borne pathogens such as malaria and
      dengue are now being complemented by the development of transgenic mosquito
      strains reprogrammed to generate beneficial phenotypes such as conditional
      sterility or pathogen resistance. The widespread success of site-specific
      nucleases such as transcription activator-like effector nucleases (TALENs) and
      clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 in model
      organisms also suggests that reprogrammable gene drive systems based on these
      nucleases may be capable of spreading such beneficial phenotypes in wild mosquito
      populations. Using the mosquito Aedes aegypti, we determined that mutations in
      the FokI domain used in TALENs to generate obligate heterodimeric complexes
      substantially and significantly reduce gene editing rates. We found that
      CRISPR/Cas9-based editing in the mosquito Ae. aegypti is also highly variable,
      with the majority of guide RNAs unable to generate detectable editing. By first
      evaluating candidate guide RNAs using a transient embryo assay, we were able to
      rapidly identify highly effective guide RNAs; focusing germ line-based
      experiments only on this cohort resulted in consistently high editing rates of 24
      90%. Microinjection of double-stranded RNAs targeting ku70 or lig4, both
      essential components of the end-joining response, increased recombination-based
      repair in early embryos as determined by plasmid-based reporters. RNAi-based
      suppression of Ku70 concurrent with embryonic microinjection of site-specific
      nucleases yielded consistent gene insertion frequencies of 2-3%, similar to
      traditional transposon- or PhiC31-based integration methods but without the
      requirement for an initial docking step. These studies should greatly accelerate
      investigations into mosquito biology, streamline development of transgenic
      strains for field releases, and simplify the evaluation of novel Cas9-based gene
      drive systems. 

PMID- 25775610
TI  - Psoriatic Nail Changes Are Associated With Clinical Outcomes in Psoriatic
      Arthritis.
AB  - BACKGROUND: Nail changes are common in psoriatic arthritis (PsA), with varying
      relationships existing between skin, nail, and joint disease. OBJECTIVE: To
      further characterize relationships between nail changes, psoriasis, and joint
      involvement in PsA patients. METHODS: One hundred eighty-eight PsA patients had
      skin, fingernail, and rheumatological assessments completed. Hand and fingernail
      photographs were taken and reviewed by a dermatologist. RESULTS: Higher swollen
      joint counts were associated with distal interphalangeal (DIP)/periungual
      psoriasis (P=.001), more splinter hemorrhages (P=.006), and any nail bed change
      (P=.03). Higher tender joint counts were associated with rough onychorrhexis
      (P<.001), DIP/periungual psoriasis (P=.03), red lunula (P=.001), nail crumbling
      (P=.046), any nail matrix (P=.03), and nail bed change (P=.03). Joint involvement
      was associated with same-digit nail changes; strongest association was swollen or
      tender DIP with subungual hyperkeratosis, odds ratio=26.6 (95% CI, 5.1-139.1).
      CONCLUSION: The DIP/periungual psoriasis and specific nail changes were
      associated with higher joint counts and certain nail changes with same-digit
      joint involvement.

PMID- 25775611
TI  - Trends in Ambulatory Health Care Usage for Adult Acne.
AB  - BACKGROUND: The prevalence of acne is increasing among young children but not
      well characterized in older patients. OBJECTIVE: To determine whether ambulatory
      health care for adult acne is increasing and whether the average age of adult
      acne patients seeking care has been increasing over time. METHODS: We performed a
      retrospective analysis of data from the 1993-2010 National Ambulatory Medical
      Care Survey for acne visits in ages 25 and older. RESULTS: Average age of adult
      acne patients increased by 0.13 years per year over the study period. Visits per
      100,000 population declined in the 25 to 34 age group (P=.05) and did not change
      significantly in the 35 to 44 and 45 and older age groups. CONCLUSIONS: The
      hypothesis that adult acne visits are increasing was not supported, but the
      average age of adult acne patients seeking care has been rising.

PMID- 25775612
TI  - Development and Validation of a Clinical Scale for the Evaluation of Forearm Skin
      Photoaging.
AB  - BACKGROUND: Despite the focus on facial photoaging ratings, there are few
      classifications developed for forearm skin aging assessment. OBJECTIVE: To
      develop and validate a clinical scale for the evaluation of forearm skin aging.
      METHODS: Three clinical dermatology faculty members selected, discussed, and
      appraised the main signs of forearm photoaging. The validation of the resulting
      scale was performed by 5 assessors who were previously trained to classify 102
      photographs of forearms with different degrees of aging. Retests were performed
      in 15 days. RESULTS: There was significant correlation between the selected
      variables and the subjective global aging scale. The developed scale showed high
      internal consistency (Cronbach's alpha=0.87) and high correlation with the global
      photoaging scale (rho=0.92). Inter- and intraobserver final scores showed high
      agreement. CONCLUSION: A validated clinical photoaging scale for forearms with
      internal consistency, reliability, and validity was developed.

PMID- 25775613
TI  - The Rise and Fall of Oral Ketoconazole.
AB  - BACKGROUND: Ketoconazole was the first broad-spectrum oral antifungal agent
      available to treat systemic and superficial mycoses. Evidence of hepatotoxicity
      associated with its use emerged within the first few years of its approval.
      Growing evidence of serious side effects including endocrine dysregulation,
      several drug interactions, and death led to the review of oral ketoconazole in
      2011. OBJECTIVE: This article chronicles the use of oral ketoconazole from its
      introduction to its near replacement in medicine. CONCLUSION: Due to its
      hepatotoxic side effects, oral ketoconazole was withdrawn from the European and
      Australian markets in 2013. The United States imposed strict relabeling
      requirements and restrictions for prescription, with Canada issuing a risk
      communication echoing these concerns. Today, oral ketoconazole is only indicated
      for endemic mycoses, where alternatives are not available or feasible. Meanwhile,
      topical ketoconazole is effective, safe, and widely prescribed for superficial
      mycoses, particularly as the first-line treatment for tinea versicolor.

PMID- 25775614
TI  - Blistering Distal Dactylitis in an Adult.
AB  - BACKGROUND: Blistering distal dactylitis is a localised infection of the anterior
      pad of the distal phalanx of the digits. It most commonly affects children and
      uncommonly adults with a history of immunosuppression or trauma. OBJECTIVE: A
      case of blistering distal dactylitis in a 32-year-old male is reported. The
      patient was not immunocompromised and did not report trauma. CONCLUSION:
      Blistering distal dactylitis may rarely present in adults (including those who
      are not immunocompromised or reporting trauma) and thus should be in the
      differential diagnosis for an adult presenting with bullae at the fingertips. The
      differential diagnosis for this presentation also includes herpetic whitlow,
      epidermolysis bullosa, bullous impetigo, and friction blisters.

PMID- 25775615
TI  - Recovery of Transplanted Eyebrow From Radiation-Induced Anagen Effluvium.
AB  - Ablative surgery for skin cancer of the face can often leave patients with
      significant deformities. These disfigurements can include loss of hair in
      conspicuous areas such as the eyebrows, leaving the patients with unsightly
      facial asymmetry. Eyebrow transplantation serves to address this issue; however,
      it has often been discouraged in patients who are destined to receive
      radiotherapy to the cutaneous area in question. This is due to the anagen
      effluvium effect of radiation therapy on hair follicles. We present a case in
      which the transplanted eyebrow hair follicles survived the deleterious effects of
      radiotherapy, leaving the patient with a symmetrical and aesthetically
      satisfactory eyebrow appearance. 

PMID- 25775616
TI  - Contact Cryoprobe Sterilization Practices: A Patient Quality and Safety Issue for
      Dermatologists.
AB  - BACKGROUND: Cryotherapy is a commonly employed treatment modality in dermatology.
      There is literature to suggest that sterilization of the contact cryotherapy
      probe is needed for proper decontamination. OBJECTIVE: To determine the status on
      the usage and sterilization methods employed by dermatology staff and residents
      affiliated with an academic training centre in Ontario, Canada, with the overall
      goal of improving patient safety. METHODS: An anonymous qualitative survey was
      conducted and analyzed. RESULTS: The survey had a response rate of 71% (n=34 of
      48); 11 of 34 physicians reported using contact cryoprobes in their practice to
      treat viral infections, benign tumours, and malignant tumours. Out of the 11
      using contact cryoprobes, 3 (27%) employed any type of cleaning method between
      patients. CONCLUSIONS: Current use of contact cryotherapy probes could be
      improved for safety considerations. Patient safety may be enhanced by the
      incorporation of routine autoclaving or other recommended decontamination methods
      of contact cryotherapy probes between patients.

PMID- 25775617
TI  - Quality of Life of Patients With Pyoderma Gangrenosum and Hidradenitis
      Suppurativa.
AB  - BACKGROUND: Pyoderma gangrenosum (PG) and hidradenitis suppurativa (HS) are
      painful and unsightly dermatologic disorders that have the potential to
      significantly decrease patients' quality of life (QOL). Due to the difficulties
      associated with curing these conditions, QOL improvement is imperative.
      OBJECTIVE: To determine if there are PG and HS disease-specific QOL measures and
      to assess whether QOL is being systematically studied in clinic populations or
      clinical trials. METHODS: A PubMed search was performed to identify QOL studies
      for patients with PG and HS. Sources from other papers were also utilized.
      RESULTS: QOL is rarely qualitatively or quantitatively assessed in HS and PG
      studies. We identified no validated disease-specific QOL measures for either PG
      or HS. CONCLUSION: Development of disease-specific QOL indices, clinical use of
      QOL measurement tool, and formal QOL evaluation in clinical trials would help to
      define the impact of PG and HS treatment in patients' lives.

PMID- 25775618
TI  - Systemic Sarcoidosis Revealed by Axillary Electrolysis.
AB  - BACKGROUND: Sarcoidosis is a noncaseating granulomatous disease that affects a
      large variety of organs and tissues. Skin sarcoidosis is commonly found in scar
      and tattooed tissues. OBJECTIVE: To report this particular case of sarcoidosis
      following electrolysis hair removal. METHOD: We report the case of a woman who
      developed sarcoidosis years after axillary electrolysis hair removal. RESULTS:
      The diagnosis of cutaneous sarcoidosis was suggested by the clinical
      manifestations and confirmed by histopathologic findings. CONCLUSION: Sarcoidosis
      should be considered during the investigation of skin lesions occurring in scar
      or traumatized tissue.

PMID- 25775619
TI  - Primary Cutaneous Carcinosarcoma of the Basal Cell Subtype Should Be Treated as a
      High-Risk Basal Cell Carcinoma.
AB  - BACKGROUND: Cutaneous carcinosarcoma is a rare primary tumor of the skin,
      characterized by biphasic epithelial and mesenchymal differentiation. OBJECTIVE:
      Due to the limited number of cases reported, there is no consensus regarding
      treatment and prognosis. Some authors suggest that cutaneous carcinosarcomas
      should be viewed as aggressive tumors, with ancillary imaging used to evaluate
      potential metastatic disease. Other reports demonstrate an indolent disease
      course, especially with epidermal-type cutaneous carcinosarcomas. METHODS: We
      report a case of cutaneous carcinosarcoma, which we treated with
      electrodessication and curettage following a shave biopsy. The tumor had an
      epithelial component resembling a basal cell carcinoma and a fibrosarcomatous
      stroma. RESULTS: At 1-year follow-up, our patient did not show evidence of
      recurrence or metastasis. CONCLUSIONS: Our case suggests that a cutaneous
      carcinosarcoma with an epithelial component composed of basal cell carcinoma can
      be regarded as a high-risk nonmelanoma skin cancer.

PMID- 25775620
TI  - Chronic Larva Currens Following Tourist Travel to the Gambia and Southeast Asia
      Over 20 Years Ago.
AB  - Larva currens is the cutaneous manifestation of human infection with the
      geotropic helminth Strongyloides stercoralis. Strongyloidiasis is a lifelong
      infection unless treated. A high index of suspicion is needed to prevent chronic
      symptoms of strongyloidiasis (eg, larva currens, eosinophilia, abdominal
      discomfort) and to prevent fatal dissemination. We present a case of chronic
      larva currens following tourist travel to the Gambia and Southeast Asia>20 years
      ago. This case highlights several important features of larva currens and
      strongyloidiasis, including the chronicity of symptoms, the rapidity of the
      migratory serpiginous rash, and the absence of high-grade eosinophilia.

PMID- 25775621
TI  - The Relationship Between Dermatologist- and Patient-Reported Acne Severity
      Measures and Treatment Recommendations.
AB  - BACKGROUND: Acne treatment recommendations for individual patients may be derived
      from multiple factors including dermatologist- and patient-reported constructs.
      OBJECTIVES: To evaluate the effects of dermatologist- and patient-reported
      measures on acne treatment recommendations by dermatologists. METHODS: An
      observational cross-sectional survey of acne patients was conducted with patient
      reported quality of life and dermatologist-reported measures of primary and
      secondary (scar) acne severity using 3 assessment approaches: maximal regional
      grade, total grade, and facial grade. RESULTS: The most highly associated factors
      with acne treatment recommendations were patient emotions, maximal regional acne
      severity, and total acne scar grade. Better acne-specific quality of life was
      negatively related to acne treatment recommendation intensity, while all 3
      grading approaches were positively related to acne treatment recommendations.
      CONCLUSIONS: For dermatologists, overall acne severity is most highly associated
      with maximal regional acne grade, total scar grade, and patient's emotional
      response to acne.

PMID- 25775622
TI  - Non-melanoma Skin Cancer in Canada Chapter 2: Primary Prevention of Non-melanoma
      Skin Cancer.
AB  - BACKGROUND: Non-melanoma skin cancer (NMSC), including basal and squamous cell
      carcinoma (BCC and SCC), represents the most common malignancy. OBJECTIVE: To
      provide guidance to Canadian health care practitioners regarding primary
      prevention of NMSC. METHODS: Structured literature searches were conducted, using
      search terms including prevention, sunscreen, and sun prevention factor. All
      recommendations concern guidance that physicians should regularly discuss with
      their patients to help establish photoprotection habits. The GRADE system was
      used to assign strength to each recommendation. RESULTS: Ultraviolet exposure is
      the major modifiable risk factor for NMSC. Aspects of photoprotection, including
      effective sunscreen use and avoidance of both the midday sun and artificial
      tanning, are discussed. Several widespread misunderstandings that undermine
      responsible public health measures related to sun safety are addressed.
      CONCLUSIONS: Photoprotection represents both an individual priority and a public
      health imperative. By providing accurate information during routine patient
      visits, physicians reinforce the need for ongoing skin cancer prevention.

PMID- 25775623
TI  - Pemphigoid nodularis.
AB  - BACKGROUND: Pemphigoid nodularis is a rare clinical variant of bullous pemphigoid
      characterized by overlapping clinical features of both prurigo nodularis lesions
      and bullous pemphigoid blisters. The condition appears to be more common in
      females and is often resistant to treatment. OBJECTIVE: To raise awareness of
      this rare variant of bullous pemphigoid. METHODS: Case report. RESULTS AND
      CONCLUSION: Dermatologists should include this variant in differential diagnosis
      of prurigo nodularis because early recognition can lead to an effective treatment
      for the prurigo component.

PMID- 25775624
TI  - Delay in Diagnosis of Congenital Linear Scleroderma until Adulthood.
AB  - BACKGROUND: Scleroderma encompasses a spectrum of disorders characterized by
      thickening of the skin and subcutaneous tissue with increased collagen
      deposition. Linear scleroderma is subdivided into progressive hemifacial atrophy
      and en coup de sabre subtype. OBJECTIVE: We report a case of congenital linear
      scleroderma identified in an adult, misdiagnosed since birth as birth trauma.
      METHODS: We completed a review of the literature for similar cases using PubMed
      and Medline. RESULTS: This is the first report of congenital linear scleroderma
      en coup de sabre diagnosed in an adult following an initial misdiagnosis of birth
      trauma. The sequelae of linear scleroderma can be significant as it can result in
      gtrth retardation, muscle atrophy, contractures, limb length discrepancy, and
      disfigurement. CONCLUSIONS: This report emphasizes the importance of educating
      practitioners about linear scleroderma. Early recognition is key as a delay in
      diagnosis can result in potentially preventable, irreversible gtrth defects and
      disfigurements.

PMID- 25775625
TI  - Molluscum-like papules as a presentation of early papulonecrotic tuberculid in
      association with nodular tuberculid in a male with asymptomatic active pulmonary
      tuberculosis.
AB  - BACKGROUND/OBJECTIVES: The clinical and histopathologic findings of a rare
      simultaneous occurrence of papulonecrotic tuberculid and nodular tuberclid in a
      patient with active but asymptomatic pulmonary tuberculosis are presented.
      Papulonecrotic tuberculid was observed at a very early stage, presenting as
      molluscum-like lesions. This has been described once in the literature. This was
      observed in conjunction with lesions compatible with the rare clinicopathologic
      variant of nodular tuberculid. Critical to the diagnosis of active pulmonary
      tuberculosis was the use of induced sputum testing, which confirmed the diagnosis
      despite the lack of a cough and a chest x-ray negative for active tuberculosis.
      METHODS/RESULTS: A 40-year-old male presented with a 2-week history of fever and
      a skin eruption consisting of molluscum-like papules on the ears, arms, and
      abdomen and nodules on his legs. Biopsies from both lesions were consistent with
      papulonecrotic and nodular tuberculid, respectively. Despite the lack of any
      respiratory symptoms, induced sputum grew Mycobacterium tuberculosis, and the
      lesions resolved on antituberculous therapy. CONCLUSIONS AND RELEVANCE:
      Tuberculids are rare in Western countries but must be considered in the
      differential diagnosis of eruptions in patients from endemic countries. An active
      tuberculous focus must be sought out.

PMID- 25775626
TI  - Remission of refractory benign familial chronic pemphigus (hailey-hailey disease)
      with the addition of systemic cyclosporine.
AB  - BACKGROUND: Benign chronic familial pemphigus (BFCP) is an autosomal dominant
      dermatosis characterized by flares of painful and often debilitating blistering
      lesions in high friction areas of the body such as the groin, axillae, lateral
      neck, and intergluteal cleft. Limited knowledge of its pathophysiology has made
      treatment of BFCP a considerable challenge and efficacy with current first line
      therapies, topical corticosteroids and antibiotics, is variable. CASE REPORT: We
      present a case of this disease in a 52 year old woman that has responded
      dramatically to the addition of oral cyclosporine to her existing regimen of oral
      acitretin, with significant improvement of skin lesions, mobility, and quality of
      life. Cyclosporine's mechanism of action in BFCP is poorly understood, although
      it possibly acts through inhibition of proinflammatory cytokines in keratinocytes
      or modulation of intracellular calcium. BFCP, the use of cyclosporine for its
      treatment, and possible mechanisms of action of cyclosporine are reviewed.

PMID- 25775627
TI  - Interleukin-17 antagonists in the treatment of psoriasis.
AB  - BACKGROUND: Psoriasis is a chronic, immune-mediated inflammatory skin disorder of
      unknown etiology. Interleukin (IL)-17a, a key product of the recently identified
      Th17 cell subset, has been found to play a critical role in the
      immunopathogenesis of psoriasis. IL-17 antagonists are a new class of biological
      agent currently in development for psoriasis that selectively inhibit IL-17a
      activity. OBJECTIVE: This review aims to summarize the current efficacy data from
      phase II randomized controlled trials of the IL-17 antagonists brodalumab,
      ixekizumab, and secukinumab for the treatment of moderate to severe psoriasis.
      CONCLUSION: Patients treated with IL-17 antagonists achieved marked reduction in
      psoriasis disease severity as demonstrated by the Psoriasis Area and Severity
      Index (PASI) 75 response rates. A sizable proportion of patients treated with
      brodalumab and ixekizumab achieved unprecedented clinical clearance of their
      psoriasis (PASI > 90). These encouraging results demonstrate the efficacy of
      these agents and validate the pro-inflammatory role of IL-17 in the
      pathophysiology of psoriasis.

PMID- 25775628
TI  - In-transit metastasis from primary cutaneous squamous cell carcinoma in a
      nonimmunosuppressed patient.
AB  - BACKGROUND: In-transit metastases are dermal and subcutanous metastatic foci
      located between the tumor and the closest regional lymph node. Although in
      transit metastasis has been commonly described for malignant melanoma, there have
      been some reports of in-transit metastases arising from primary cutaneous
      malignancies. The risk of development of in-transit metastases is higher in
      patients with high-risk squamous cell carcinoma. CASE REPORT: We present a case
      of in-transit metastasis in a nonimmunosuppressed patient with a primary
      cutaneous squamous cell carcinoma.

PMID- 25775629
TI  - Acitretin-induced hepatitis: when to monitor cholestatic enzymes.
AB  - IMPORTANCE: Acitretin is a systemic retinoid that is used in dermatology for a
      variety of conditions. A well-recognized potential adverse event from acitretin
      is elevated transaminases, indicating acute hepatocyte damage. Less well known is
      the possible cholestatic injury that can occur, signaled by elevated gamma
      glutamyltransferase (GGT) and alkaline phosphatase (ALP). OBSERVATIONS: Our
      patient presented with an acute acitretin-induced hepatitis with a mixed pattern
      of elevated transaminases as well as GGT and ALP. A literature review
      demonstrated that most cases of acitretin-induced hepatitis, outside clinical
      trials, describe patients with a similar mixed hepatitis pattern. CONCLUSIONS:
      This is the first literature review on acitretin-induced hepatitis. Although
      acitretin-induced hepatoxicity is rare, the seemingly unusual presentation of a
      mixed pattern of hepatocyte injury and cholestasis may be more common than
      previously thought. The findings should encourage clinicians not only to monitor
      transaminases but also to consider measuring cholestatic enzymes (ALP/GGT) in
      patients with transaminase abnormalities.

PMID- 25775630
TI  - Diseases of abnormal sensitivity to cold in children on psychostimulant drugs.
AB  - BACKGROUND: Oral psychostimulant (PS) drugs, the pharmacologic treatment of
      choice for attention-deficit/hyperactivity disorder (ADHD), have been associated
      with diseases of abnormal sensitivity to cold (DASC) such as Raynaud phenomenon
      and acrocyanosis. OBJECTIVES: In a cohort of pediatric patients with DASC, we
      sought to identify prevalence and clinical features of patients on PS drugs.
      METHODS: A 6-year retrospective chart review (2005-2011) of Ste-Justine
      University Hospital Center DASC patients with and without exposure to PS drugs
      was performed. Clinical data were analyzed with descriptive statistical methods.
      RESULTS: Of 43 patients with DASC, 11 (25%) were exposed to PS drugs. In this
      group males were overrepresented, there was no evidence of collagen vascular
      diseases, serologic findings were not significant and the mean duration of PS
      intake was of 2.5 years. DASC age of onset was similar in both exposed and
      nonexposed patients. The incidence of more than one DASC type was greater in
      teenager patients with a positive family history of autoimmune and/or collagen
      vascular diseases. LIMITATIONS: This study is limited by its small population
      size, short follow-up period and its retrospective nature. CONCLUSION: Physicians
      should be aware of PS drugs as possible triggers for DASC.

PMID- 25775631
TI  - Pyoderma Gangrenosum among Patients with Inflammatory Bowel Disease: A
      Descriptive Cohort Study.
AB  - BACKGROUND: Pyoderma gangrenosum (PG) is a severe extraintestinal manifestation
      of inflammatory bowel disease (IBD). OBJECTIVE: To better characterize PG
      features and management among an IBD cohort. METHODS: Subjects with PG were
      identified using a large database at a tertiary center. Patient demographics and
      clinical characteristics were summarized using descriptive statistics. RESULTS:
      Eighty patients with an episode(s) of PG were identified, yielding an overall
      prevalence of 1.9%. Overall, 93% of patients with PG had some degree of colonic
      inflammation. Thirty-one (39%) patients required hospitalization for PG.
      Underlying bowel disease was active at the time of PG episode(s) in 52 (65%)
      patients. The PG location was variable, with the lower extremity being the most
      common. Most patients (71.3%) required multiple therapies to achieve PG healing.
      CONCLUSIONS: We describe one of the largest case series of PG among patients with
      IBD. The variety of treatment strategies used highlights the lack of clear
      guidelines in managing this complex group of patients.

PMID- 25775632
TI  - Tinea cruris and tinea corporis masquerading as tinea indecisiva: case report and
      review of the literature.
AB  - BACKGROUND: Tinea indecisiva is characterized by concentric scaly rings
      simulating tinea imbricata but caused by dermatophytes other than Trichophyton
      concentricum. OBJECTIVE: Tinea indecisiva has been rarely reported. We report a
      unique case and review of the previously reported cases, pathogenesis, and
      management. METHODS: An adult Indian man developed extensive tinea cruris and
      tinea corporis with concentric rings of scaly lesions over the groin, buttocks,
      and thighs following the use of oral corticosteroids and antifungal-steroid cream
      for 3 months. Mycologic and immunologic studies were performed for diagnosis.
      RESULTS: Diagnosis of tinea indecisiva was confirmed on the appearance of "ring
      within-a-ring" lesions clinically and isolation of Trichophyton mentagrophytes
      var. interdigitale as the etiologic agent on mycologic testing. Intradermal
      testing with Trichophyton extract showed fluctuating hypersensitivity responses.
      Four-week treatment with daily oral terbinafine resulted in complete resolution.
      CONCLUSION: Tinea indecisiva should be considered in a patient with tinea
      imbricata-like lesions with local immunosuppression caused by a non-concentricum
      dermatophyte.

PMID- 25775633
TI  - Uncommon responses of segmental vitiligo to melanocyte-keratinocyte
      transplantation procedure.
AB  - BACKGROUND: Patients with segmental vitiligo (SV), unlike those with nonsegmental
      vitiligo (NSV), have a more predictable course and are more responsive to
      surgery. OBJECTIVE: To report 10 patients with SV treated with the melanocyte
      keratinocyte transplantation procedure (MKTP), who responded with unusual
      responses not previously reported in the literature. METHODS: This is a
      retrospective, observational study that reports 10 patients with SV who underwent
      the MKTP between May 2003 and May 2012. RESULTS: Two patients had successful
      repigmentation after split-thickness skin grafting after failure of the MKTP. Two
      patients developed a hypopigmented ring at a margin of the MKTP-treated area. One
      patient had complete repigmentation after a second MKTP. Two patients developed
      koebnerization of the recipient site. Three patients developed new vitiligo
      patches in previously unaffected areas after the MKTP. CONCLUSIONS: Uncommon and
      even suboptimal responses can occur following the MKTP in SV patients. There is a
      need for studies to provide better understanding and outcomes for SV patients
      undergoing the MKTP.

PMID- 25775634
TI  - Evaluation of the efficacy and safety of topical imiquimod 5% for plaque-type
      morphea: a multicenter, prospective, vehicle-controlled trial.
AB  - BACKGROUND: There is currently a lack of evidence-based therapies that are safe
      and effective for plaque-type morphea. We aimed to evaluate the therapeutic
      potential and safety profile of imiquimod 5% cream in plaque-type morphea.
      METHODS: We enrolled 25 adult patients from two Canadian centers with
      histologically confirmed plaque-type morphea. Imiquimod 5% was applied to a
      representative plaque, and vehicle was applied to a control plaque for 9 months.
      Treatment efficacy was assessed with the Dyspigmentation, Induration, Erythema,
      and Telangiectasias (DIET) score, histology, and ultrasound evaluation. RESULTS
      AND CONCLUSIONS: Twenty-two patients completed the entire length of the study.
      Imiquimod 5% was superior to vehicle in reducing DIET scores at 3, 6, 9, and 12
      months (p < .05). Induration demonstrated the greatest response. Histologic
      evaluation showed significant improvement or resolution of disease. However, no
      ultrasonographic differences were found in dermal and hypodermal thicknesses
      between the treatment and vehicle groups (p > .05). Adverse effects were minimal
      and well tolerated.

PMID- 25775635
TI  - Evaluation between Association of Psoriasis and Vitiligo.
AB  - BACKGROUND: Although the occurrence of psoriasis and vitiligo is reported in a
      few studies, no proper relationship has been found between these two diseases.
      OBJECTIVE: The aim of this study was to identify the frequency of the coincidence
      of these two diseases. METHOD: A descriptive and cross-sectional study was
      conducted on 6,200 patients referred to dermatology clinics from September 2004
      to June 2005. RESULTS: Among these patients, 219 and 154 patients suffered from
      psoriasis (3.53%) and vitiligo (2.48%), respectively, and 12 patients (0.19%) had
      psoriasis and vitiligo simultaneously. The coincidence in the psoriasis group was
      5.48% and in the vitiligo group was 7.79%, so the coincidence of both diseases
      was greater than the incidence of each alone. This association was significant (p
      = .004). CONCLUSION: Coincidence of these two diseases was seen, but more studies
      should be done to find common genetic and immunologic factors.

PMID- 25775636
TI  - Low glutathione peroxidase activity levels in patients with vitiligo.
AB  - BACKGROUND: Vitiligo is an idiopathic skin disease characterized by white areas
      on the skin due to loss of the functional melanocytes, with possible involvement
      of oxidative stress. Glutathione peroxidase (GPx) is an antioxidant enzyme that
      protects cells against oxidative damage. AIM: To examine serum GPx levels in
      patients with vitiligo and to relate the findings to the clinical features.
      PATIENTS AND METHODS: The study group included 60 patients with vitiligo and 30
      matching healthy controls. GPx activity was evaluated using enzyme-linked
      immunosorbent assay. RESULTS: We found a significant decrease in serum GPx
      activity level in the patients with vitiligo compared to the healthy controls
      (0.29 +/- 0.14 versus 0.47 +/- 0.13, p < .001). The levels were significantly low
      in skin phenotypes III and IV (p < .001). Higher levels were also observed with
      increasing age (>= 14 years), prolonged disease duration (>= 3 years), and
      generalized and extensive vitiligo (< 50%). However, these variations were
      statistically insignificant. CONCLUSIONS: Low levels of serum GPx activity,
      indicative of a disturbed oxidant-antioxidant system, may contribute to the
      development of vitiligo.

PMID- 25775637
TI  - Skin Necrosis from Intra-articular Hyaluronic Acid Injection.
AB  - BACKGROUND: Tissue necrosis is a rare yet potentially serious complication of
      intra-articular (IA) hyaluronic acid (HA) injections for treatment of knee
      osteoarthritis. OBJECTIVE: To report a case of a patient with cutaneous necrosis
      after IA HA injection for treatment of knee osteoarthritis, presenting as a
      livedoid violaceous patch on the right knee. METHOD: We report a case of
      cutaneous necrosis as a rare complication of IA HA injection for treatment of
      knee osteoarthritis. A literature review was undertaken of similar cases.
      RESULTS: Use of HA IA injections in the treatment of osteoarthritis can result in
      similar skin necrosis at uncommon anatomic locations corresponding to the site of
      HA injection. CONCLUSION: Although tissue necrosis is a rare complication,
      physicians need to be aware of this possibility as a complication of HA IA
      injections in the treatment of osteoarthritis and should be mindful of potential
      treatment options to manage this adverse event.

PMID- 25775638
TI  - POEMS Syndrome Complicated by Extensive Calciphylaxis: A Remarkable Recovery.
AB  - BACKGROUND AND OBJECTIVE: Calciphylaxis is life threatening. It has traditionally
      been associated with end-stage renal disease and hyperparathyroidism but is
      increasingly common in other clinical contexts. The association of
      polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin
      changes (POEMS) syndrome and calciphylaxis has been reported only in a few cases.
      This case is the first of patient survival in such widespread disease. METHODS
      AND RESULTS: A 42-year-old man with POEMS syndrome developed extensive
      calciphylaxis despite normal renal and parathyroid function. Rapid diagnosis,
      treatment, and supportive care contributed to full clinical resolution.
      CONCLUSION: This is the fifth case of POEMS syndrome associated with
      calciphylaxis. The observations from this report suggest that POEMS syndrome
      might be an independent risk factor for the development of calciphylaxis. This
      case underlines the importance of careful follow-up in patients with POEMS
      syndrome and prompt diagnosis and treatment of associated calciphylaxis.

PMID- 25775639
TI  - Prevalence of rosacea in community settings.
AB  - BACKGROUND: The prevalence of rosacea is poorly characterized. Because selection
      bias may affect prevalence estimates, there is a need to characterize the
      prevalence of rosacea outside the clinic setting. OBJECTIVE: To assess the
      prevalence of rosacea in community settings. METHODS: A clinical research fellow
      and a medical student stood in public places (a mall, the Department of Motor
      Vehicles, a grocery store) and examined consecutive individuals who passed by <=
      2 yards away. They tallied demographic and descriptive data on the subject and
      included the subject in one of three categories: clearly rosacea, possible
      rosacea, and definitely no rosacea. Subanalyses by perceived gender, age, race,
      and rosacea subtype were also performed. Comparisons between groups were made
      using the Fisher exact test. RESULTS: Considering the prevalence of rosacea among
      all observed individuals in the community setting, 5.4% (95% CI 3.6-7.8) of
      individuals had "possible" rosacea and 6% (95% CI 4.1-8.5) of individuals had
      "definite" rosacea. Older, white individuals with fairer skin types (Fitzpatrick
      skin types I, II, and III) were more likely to have rosacea. There was no gender
      predisposition. LIMITATIONS: Distance from subjects made it difficult to assess
      patients with mild rosacea or a few telangiectasias, as well as ocular rosacea.
      The study could not assess those individuals who were too embarrassed by their
      rosacea to be in the public settings observed. Additionally, some subjects may
      have applied significant makeup in an effort to conceal their rosacea, making
      assessment difficult. CONCLUSIONS: Based on direct observation of individuals in
      community settings, rosacea is more common than previously reported in the United
      States.

PMID- 25775640
TI  - Management of Onychomycosis in Canada in 2014.
AB  - BACKGROUND: Onychomycosis has several clinical presentations and is caused by
      various infectious organisms. OBJECTIVE: To provide guidance for selection of
      appropriate treatment. METHODS: The literature on onychomycosis management was
      reviewed to generate an evidence-based decision tree. RESULTS AND CONCLUSION:
      Several options are available: terbinafine, itraconazole, fluconazole, ciclopirox
      8% nail lacquer, efinaconazole 10% nail solution, and laser therapy. Further
      studies on lasers are needed before use can be recommended. Nondermatophyte molds
      or mixed infection can be managed with terbinafine or itraconazole with or
      without topicals. Itraconazole, fluconazole, and efinaconazole can be used for
      Candida infection. For dermatophytes, topicals can be considered for mild to
      moderate onychomycosis. For moderate to severe cases, any oral monotherapy can be
      used; however, we suggest terbinafine if there is a possibility of a drug
      interaction. These recommendations can be applied for all ages, immune function,
      or metabolic status, but proper monitoring and contraindications should be taken
      into consideration.

PMID- 25775641
TI  - Cost and Resource Use of Pemphigus and Pemphigoid Disorders Pre- and Post
      Rituximab.
AB  - BACKGROUND: Rituximab (RTX) is increasingly used for the treatment of pemphigus
      and pemphigoid disorders. The high cost of RTX frequently limits its use and
      access. OBJECTIVE: To determine the health system resources and costs associated
      with RTX treatment of pemphigus and pemphigoid. METHODS: Health system resources
      and costs attributed to a convenience sample of 89 patients with either pemphigus
      or pemphigoid were identified, quantified, and valued 6 months prior to and
      following RTX initiation between May 2006 and August 2012. Overall cohort costs
      and costs per patient were calculated (2013 Can$). RESULTS: The overall cohort
      cost for 6 months pre-RTX was $3.8 million and for 6 months post-RTX was $2.6
      million. The average cost per patient decreased from $42,231 to $29,423 (30.3%
      decrease). The main cost driver was intravenous immunoglobulin. CONCLUSIONS: Our
      findings suggest that RTX is effective in reducing health system resources and
      the costs associated with the treatment of pemphigus and pemphigoid.

PMID- 25775642
TI  - Dermatologic Surgical Pearls: Tips for Closing a Defect under Tension.
AB  - Dermatologic surgery procedures can sometimes be time consuming in an office
      setting. We present a series of tips for dermatologists and dermatologic surgeons
      that will enhance the efficiency of simple procedures. This article reviews three
      methods to aid in the closure of defects under tension. 

PMID- 25775643
TI  - Dermatologic Surgical Pearls: Enhancing the Efficacy of the Traditional
      Elliptical Excision.
AB  - Dermatologic surgery procedures can sometimes be time consuming in an office
      setting. We present a series of tips for dermatologists and dermatologic surgeons
      that will enhance the efficiency of simple procedures. 

PMID- 25775644
TI  - Dermatologic Surgical Pearls Part 3: Tips for Labial Excisions and Repairs.
AB  - Dermatologic surgery procedures can sometimes be time consuming in an office
      setting. We present two tips for dermatologists and dermatologic surgeons that
      will enhance the efficiency of procedures around the lip. 

PMID- 25775645
TI  - Dermatologic Surgical Pearls Part 4: Tips for Full-Thickness Skin Grafts.
AB  - Dermatologic surgery procedures can sometimes be time consuming in an office
      setting. We present a series of tips for dermatologists and dermatologic surgeons
      that will enhance the efficiency of skin graft procedures. 

PMID- 25775646
TI  - Pigmented Mammary Paget Disease Mimicking Superficial Spreading Melanoma in an
      Elderly African-American Female.
AB  - BACKGROUND: Pigmented mammary Paget disease (PMPD) is a rare disease that may
      mimic cutaneous melanoma both in clinical presentation and on histology.
      OBJECTIVE: The goal of this study was to discuss the clinical and histologic
      similarities between PMPD and cutaneous melanoma and how to differentiate between
      the two diseases. METHODS: We describe an African-American patient with PMPD who
      was thought to have cutaneous melanoma on presentation. We describe the
      similarities of PMPD to cutaneous melanoma both clinically and on histology and
      discuss the methods of differentiation. RESULTS: Clinical examination revealed a
      large pigmented patch of the left breast that appeared asymmetrical with
      irregular borders with a highly variable color pattern throughout. Histologic
      evaluation showed characteristics shared between PMPD and cutaneous melanoma.
      Immunohistochemical staining was needed for differentiation. CONCLUSION: PMPD is
      a rare disease and is similar in clinical presentation and on histology to
      cutaneous melanoma. Immunohistochemical staining must be used to differentiate
      between the two diseases.

PMID- 25775647
TI  - Multiple Cutaneous Creamy Papules and Nodules: A Case of Miliarial Gout.
AB  - BACKGROUND: Tophaceous gout is the nonarticular deposition of monosodium urate
      resulting from a disorder in purine metabolism that causes an elevation of serum
      uric acid. Cutaneous variants of tophaceous gout include papular, nodular,
      ulcerative, and pustular forms. OBJECTIVE: We present a case of a 67-year-old man
      who presented with multiple cutaneous creamy white papules and nodules. A biopsy
      was taken, and a diagnosis of cutaneous tophaceous gout was made. The treatment
      and pathophysiology are discussed. CONCLUSION: Miliarial gout is a rare form of
      cutaneous tophaceous gout that is treated using xanthine oxidase inhibitors such
      as allopurinol and febuxostat or uricosurics such as probenecid.

PMID- 25775648
TI  - Paradoxical, Cupping-Induced Localized Psoriasis: A Koebner Phenomenon.
AB  - BACKGROUND: Cupping therapy is a traditional Chinese medicine used to heal
      psoriasis. The Koebner phenomenon is the occurrence of psoriatic lesions at the
      site of cutaneous injury. OBJECTIVE: To describe the first case of biopsy-proven
      cupping-induced localized psoriasis, an example of the Koebner phenomenon.
      METHODS: The histopathology of the lesions is described. A brief review of the
      literature regarding cupping therapy and its efficacy are discussed. RESULTS: A
      45-year-old Asian male presented himself to the dermatology clinic for further
      treatment of his psoriasis. Four unusually circular plaques on the lower back
      were discovered. Pathologic diagnosis revealed an early lesion of psoriasis. on
      further inquiry, the patient admitted to undergoing a recent "cupping" procedure
      in an attempt to cure his condition. CONCLUSION: The efficacy of cupping therapy
      is controversial, and psoriatic patients may develop localized psoriasis through
      koebnerization as a result of cupping therapy rather than achieve desirable
      therapeutic benefits.

PMID- 25775649
TI  - The Prevalence of Anxiety and Depression in Arab Dermatology Patients.
AB  - BACKGROUND: Psychiatric disorders are common among patients with physical
      illnesses. OBJECTIVES: To estimate the prevalence of anxiety and depression in
      Arab dermatology patients and to study its association with the patients'
      characteristics. MATERIALS AND METHODS: A cross-sectional study was carried out
      on 875 patients attending the Dermatology Clinic at King Khalid University
      Hospital in Riyadh, Saudi Arabia. Each patient was asked to complete the Hospital
      Anxiety and Depression Scale and the demographic-clinical questionnaire. RESULTS:
      The frequency of anxiety and depression in Arab dermatology patients was 29% for
      anxiety and 14% for depression. These frequencies were not related to
      sociodemographic and clinical variables (p>.05), except skin disease type
      (p<.05). Patients suffering from hair loss had the highest anxiety and depression
      scores (OR 1.725 [95% CI 1.247-2.386] and OR 1.686 [95% CI 1.101-2.581],
      respectively). On the other hand, patients suffering from psoriasis had the
      highest depression scores (OR 2.909 [95% CI 1.611-5.254]). CONCLUSION: Anxiety
      and depression are frequent among Arab dermatology patients.

PMID- 25775650
TI  - Public Engagement with Dermatology Contents on Facebook.
AB  - BACKGROUND: The gtring presence of dermatology platforms on Facebook has been
      acknowledged; however, little is known about the extent to which different types
      of content influence the level of engagement with online users. OBJECTIVE: To
      assess the level of public engagement with different types of content posted on
      Facebook pages devoted to dermatology. METHODS: A search on Facebook identified
      existing pages for dermatology academic journals, professional societies, and
      patient-centered groups. Then the engagement rate was calculated for each content
      type published on the selected pages. RESULTS: The median engagement rates were
      63.8% for educational posts, 41.3% for interactive posts, 27.4% for news
      articles, 11.8% for academic articles, and 9.3% for others. CONCLUSION:
      Educational posts engaged with online users the most effectively. The level of
      engagement is a key determinant of knowledge dissemination via online tools, and
      the type of content may influence the level of engagement.

PMID- 25775651
TI  - Generalized Multinucleate Cell Angiohistiocytoma.
AB  - BACKGROUND: There are less than 100 cases of multinucleate cell angiohistiocytoma
      (MCA) currently reported in the literature. It occurs as a localized,
      asymptomatic, benign proliferation of the skin, characterized histologically by
      irregular multinucleate cells. Due to its novelty, the etiology of the disease
      and treatment options are still under investigation. OBJECTIVE: To report a case
      of confirmed, generalized MCA along with a review of the literature on the
      histology, immunology, potential etiology, and treatment of MCA. OBSERVATIONS:
      The patient was a 41-year-old female with asymptomatic violaceous plaques found
      on the extensor arms, legs, and trunk. Histopathology revealed increased dilated
      vascularity and cellularity (composed of mononuclear histiocytes and a few
      angulated multinucleated giant cells) in the dermis. CONCLUSIONS: Overall, MCA is
      a poorly understood, distinct dermatologic phenomenon. Here we present a case of
      generalized MCA to further the understanding of this disease presentation.

PMID- 25775652
TI  - Recall Dermatitis to Metronidazole.
AB  - BACKGROUND AND OBJECTIVE: Recall dermatitis is an uncommon entity that has been
      noted with patch testing, repeat exposures to a medication or allergen, and the
      concurrent use of ultraviolet radiation and certain medications. Recall
      dermatitis from primary cutaneous exposure and subsequent oral exposure are rare,
      and the etiology remains unknown. CONCLUSION: We report a case of recall
      dermatitis with a drug eruption secondary to metronidazole. Therapy with this
      medication was initially topical for rosacea and subsequently oral for a
      gastrointestinal infection. This case draws attention to the use of metronidazole
      and the risk of recall dermatitis.

PMID- 25775653
TI  - Granular Cell Tumor on the Chest of a 9-Year-Old Female: Case Report and a
      Retrospective Analysis.
AB  - BACKGROUND: Granular cell tumor is a benign tumor originating from Schwann cells.
      Children and adolescents are rarely affected. We report a 9-year-old female who
      presented with a cutaneous granular cell tumor on the chest. OBJECTIVE: To
      determine the incidence of granular cell tumor and proportion of tumors seen in
      the pediatric population at our center. METHODS: We retrospectively reviewed the
      surgical pathology records from 1997 to 2014 at our center. RESULTS: The
      incidence of granular cell tumor is five cases per million person-years (95% CI 3
      8). Of the 18 cases, 9 cases occurred in the pediatric population. CONCLUSION:
      Fifty percent of granular cell tumor cases diagnosed at our center occurred in
      the pediatric population. Granular cell tumor may not be as rare as we expect in
      the pediatric population.

PMID- 25775655
TI  - Adhesive retention tape supporting atrophic skin on a tripolar advancement flap:
      a novel wound closure option for atrophic skin in an aging population.

PMID- 25775656
TI  - Re: "Erythema Annulare Centrifugum due to Pegylated Interferon-alpha-2a plus
      Ribavirin Combination Therapy in a Patient with Chronic Hepatitis C Virus
      Infection".

PMID- 25775657
TI  - Prevention of alopecia in medical and interventional chemotherapy patients.
AB  - BACKGROUND: Chemotherapy-induced alopecia is one of the most distressing side
      effects of cancer treatment. Although there have been a number of investigated
      strategies to reduce this, there is no standard of care for treatment. OBJECTIVE:
      This review aims to summarize the relevant evidence for the treatments available
      for chemotherapy-induced alopecia. METHODS: A literature search using PubMed and
      the MEDLINE subengine was completed. The terms "chemotherapy," "alopecia,"
      "quality of life," and "strategies" were used, and articles from the last 10
      years were considered. The pediatric population was not investigated. RESULTS:
      Physical therapies for alopecia prevention have shown some promise but range from
      insufficient to detrimental depending on the type of cancer. Cold caps may be
      more effective than tourniquets and may be associated with fewer metastatic
      events. Pharmacologic therapies, both immunomodulators and growth factors, have
      stood the test of several trials to date. In particular, cyclosporine has been
      shown either to prevent alopecia or promote hair growth during a chemotherapy
      regimen. CONCLUSION: Although the evidence is not yet overwhelming, it is
      becoming clear that a combination of mechanical and chemical interventions may
      help compensate for the downfalls of either therapy alone.

PMID- 25775658
TI  - Progression of surgical hair restoration techniques.
AB  - BACKGROUND: Early surgical hair restoration (SHR) techniques were fraught with
      limitations. Major advancements and refinements have taken place yielding
      minimally invasive, relatively scar-free, and natural-looking hair
      transplantations. OBJECTIVE: Our aim was to review the origins and advancements
      of SHR and to discuss future directions for the field. METHODS: Searches were
      performed using: Pubmed, Scopus, and the International Society of Hair
      Restoration Surgery's Hair Transplant Forum International for articles related to
      SHR. Reference sections of articles obtained were reviewed. Relevant textbooks
      obtained were reviewed. RESULTS AND CONCLUSION: SHR techniques originated as
      macro-level graft transplantations and excision of scalp tissue. They progressed
      toward micro-level graft transplantations performed with extreme caution and
      precision. However, all SHR techniques are limited by their reliance on existing
      donor hair to fill balding areas. Further advancements in hair follicle cell
      cloning and regeneration of growth may offer a solution to this overarching
      limitation.

PMID- 25775659
TI  - Think beyond the Skin: 2014 Canadian Expert Opinion Paper on Treating to Target
      in Plaque Psoriasis.
AB  - OBJECTIVE: Explore the feasibility of Treat to Target in the area of psoriasis as
      seen in other therapeutic areas such as hypertension, hyperlipidemia, diabetes
      and rheumatoid arthritis. METHODS: Review validated, measurable targets for
      psoriasis, including physician global assessment (PGA), psoriasis area and
      severity index (PASI) and dermatology life quality index (DLQI). Examine
      principles brought forth in the published European consensus on psoriasis and
      develop a Canadian consensus on Treat to Target in psoriasis. RESULTS: As PASI
      and DLQI are not routinely used in the community setting, we are recommending
      target at a PGA of zero (clear). CONCLUSION: Recommend that the target is a PGA
      of zero (clear) as it provides a simple and measurable result that the patient
      and physician can clearly understand.

PMID- 25775660
TI  - A clinicopathologic review of a case series of dermatofibrosarcoma protuberans
      with fibrosarcomatous differentiation.
AB  - BACKGROUND: Dermatofibrosarcoma protuberans with fibrosarcomatous differentiation
      (DFSP-FS) is a rare variant of DFSP with a more aggressive clinical course,
      characterized by higher rates of local recurrence, metastasis, and death.
      METHODS: We conducted a clinicopathologic review of all DFSP-FS cases that
      occurred in Alberta, Canada, from 1997 to 2007. RESULTS: Of the 75 DFSP cases
      reviewed, 4 demonstrated fibrosarcomatous differentiation. Three patients were
      female and one was male, and the age range was 25 to 76 years. Three tumors
      invaded to skeletal muscle, whereas one invaded to subcutaneous tissue only.
      Although perineural invasion was noted in all four cases, none exhibited
      lymphovascular space invasion. One local recurrence developed, and two of four
      tumors metastasized. Metastasis was associated with tumor size, tumor necrosis,
      grenz zone involvement, ulceration, thickness, and tumor grade. One patient died
      within 5 years of diagnosis. CONCLUSION: DFSP-FS represents a more aggressive
      subtype of DFSP. Several features of DFSP-FS may impart a higher risk of
      metastasis.

PMID- 25775661
TI  - Comparison of lesion improvement in lupoid leishmaniasis patients with two
      treatment approaches: trichloroacetic Acid and intralesional meglumine
      antimoniate.
AB  - BACKGROUND: There are several therapies for treating lupoid leishmaniasis. We
      compared the effectiveness of intralesional meglumine antimoniate (MA) and
      topical application of trichloroacetic acid (TCA) 50% solution. METHODS: This
      study was a randomized clinical trial comprising 60 lupoid leishmaniasis
      patients. The first group received intralesional MA once a week, and the second
      group was treated once weekly with TCA 50% topical solution. The results were
      recorded once after 8 weeks and then 3 months after the termination of treatment.
      RESULTS: The total clearance rates after treatment and after the 3-month follow
      up were, respectively, 48.1% and 40% in the first group and 44.4% and 36.6% in
      the second group. There was no significant difference between the two treatment
      groups (p=.25 and p=.26). In both groups, the most common side effect was
      scarring. CONCLUSION: Having almost the same efficacies, TCA as a topical
      approach could be as effective as MA in the lupoid leishmaniasis treatment plan.

PMID- 25775662
TI  - Correlation between Socioeconomic Status and Clinical Course in Patients with
      Cutaneous Leishmaniasis.
AB  - OBJECTIVE: Leishmaniasis has long been known as a poverty-associated disease,
      which is particularly prevalent in developing and less developed countries. The
      role of socioeconomic status in the clinical course of the disease is less
      clearly defined. In this study, we investigated the potential relationship
      between the clinical course of cutaneous leishmaniasis in terms of its evolution
      into chronic forms and the socioeconomic status of the patients. METHODS: A total
      of 140 patients attending the dermatology clinic in Imam Reza Hospital, Mashhad,
      Iran, were enrolled. The patients were grouped into high, medium, and low
      socioeconomic classes according to a comprehensive questionnaire. They received
      routine treatment protocols for leishmaniasis and were followed up for 1 year.
      RESULTS: We found a statistically significant relationship between the clinical
      course of the disease and socioeconomic status. CONCLUSION: Poverty might prolong
      the course of cutaneous leishmaniasis for many different reasons.

PMID- 25775663
TI  - Retrospective Review of Folliculitis Decalvans in 23 Patients with Course and
      Treatment Analysis of Long-standing Cases.
AB  - BACKGROUND: To date, there is no standard treatment of folliculitis decalvans
      (FD), a rare type of cicatricial alopecia. OBJECTIVE AND METHODS: The records of
      23 patients with FD (1998-2012) were retrospectively analyzed, with added data
      review on the course and treatment of long-standing cases. RESULTS: Initial
      management consisted mostly of intralesional triamcinolone acetonide, clobetasol
      lotion, and either cephalexin, minocycline, doxycycline, or tetracycline.
      Alternatives consisted of rifampicin, clindamycin, ciprofloxacin, and
      isotretinoin. Remission was achieved in weeks to months in more than half of the
      cases, with low occurrence of relapse. The poor responders had a protracted
      course of temporary improvement and multiple relapses. CONCLUSION: The majority
      of patients showed improvement and subsequent remission with oral antibiotics. In
      some patients, it took years of slow taper before the antibiotic could be
      discontinued. Only a few patients had recalcitrant disease, with minimal response
      to their initial and alternative medications.

PMID- 25775664
TI  - Treatment of vitiligo patients by excimer laser improves patients' quality of
      life.
AB  - BACKGROUND: Vitiligo can negatively affect patients' quality of life (QoL).
      Assessment of QoL provides relevant information about treatment benefits.
      OBJECTIVES: To examine the effects of excimer laser treatment on vitiligo
      patients' QoL and to identify overall patient satisfaction. The literature review
      failed to show any study concerning the same field. METHODS: A total of 134
      vitiligo patients (with 386 lesions) were studied. The Dermatology Life Quality
      Index (DLQI) was used to assess the effect of excimer laser treatment on
      patients' QoL. A visual analogue scale (VAS) was used to rate patients' overall
      life satisfaction and disturbance. RESULTS: Excimer laser treatment significantly
      improved QoL in vitiligo patients, with improvement observed in five of six DLQI
      domains. Treatment-induced changes in the VAS score showed a significant decline
      in life disturbance and improvement in life satisfaction. Multivariate analysis
      revealed that sex and treatment duration were independent factors influencing
      treatment outcomes. CONCLUSIONS: Treatment of vitiligo with excimer laser can
      positively influence patients' QoL. Patients with multiple focal lesions should
      be treated by excimer laser even if some lesions may not show significant
      clinical improvement.

PMID- 25775665
TI  - PCQoL: A Quality of Life Assessment Measure for Pachyonychia Congenita.
AB  - BACKGROUND: Pachyonychia congenita (PC) is a rare but often debilitating,
      dominantly inherited disorder. New treatments require more accurate instruments
      for evaluating changes in the quality of life in these patients. OBJECTIVES: This
      study was undertaken to develop and validate a quality of life questionnaire for
      PC patients (PCQoL). METHODS: Relevant factors influencing quality of life in PC
      patients were identified and incorporated into the well-recognized, general
      questionnaire, the Dermatology Life Quality Index (DLQI), to establish a disease
      specific measure, the PCQoL. Classical test theory (CTT) and Rasch analysis (RA)
      were used to analyze and validate the PCQoL. RESULTS: CTT analysis established
      test-retest reliability and internal consistency for the PCQoL. Concurrent and
      construct validity for the DLQI and the PCQoL were also validated. Chi-square
      based infit and outfit statistics indicated that the Rasch model fits the
      observed responses very well. RA reconfirmed reliability, internal consistency,
      reasonable homogeneity, construct validity, and the presence of three RA-based
      domains. CONCLUSION: The PCQoL questionnaire is a measure validated by both CTT
      and RA. It appears to be a valuable tool in measuring quality of life
      modifications in PC individuals with keratoderma.

PMID- 25775666
TI  - Trichodysplasia spinulosa in a renal transplant patient.
AB  - BACKGROUND: Trichodysplasia spinulosa (TS) is a rare skin affection seen in
      immunocompromised patients, mainly those with solid organ tranplants. OBJECTIVE:
      To report a case of a patient with classic clinical and pathologic findings for
      the disease so that physicians caring for this population are aware of the
      clinical presentation. METHOD: We report the case of a female patient we saw at
      our clinic with a diagnosis of TS. RESULTS: The diagnosis of TS was confirmed by
      pathologic findings. CONCLUSION: TS should be considered in any immunocompromised
      patient with a papular facial eruption reminiscent of acne vulgaris and with
      keratotic spiny papules as a distinctive feature.

PMID- 25775667
TI  - Hypopigmented segmental Darier disease.
AB  - BACKGROUND: Darier disease is a genodermatosis caused by a mutation in the ATP2A2
      gene. It classically presents as hyperkeratotic greasy papules in a seborrheic
      distribution. Several variants have been reported, notably the hypopigmented
      variant, which predominantly targets dark-skinned individuals, and a segmental
      variant that often follows the lines of Blaschko. METHODS: We report a case of a
      41-year-old African-Canadian female with a long-standing history of macular
      hypopigmented pruritic eruption following the lines of Blaschko on her back. The
      eruption was persistent and recalcitrant to various treatments. Dyskeratosis with
      corps ronds and grains, acantholysis, and parakeratosis were observed on
      histopathology. Those findings were consistent with the diagnosis of segmental
      hypopigmented Darier disease. RESULTS AND CONCLUSIONS: To our knowledge, this is
      the first case reporting a combined segmental and hypopigmented variant of Darier
      disease. We further present a literature review for hypopigmented and segmental
      variants of Darier disease.

PMID- 25775668
TI  - Photo developer allergic contact dermatitis in a photographer following
      paraphenylenediamine sensitization from a temporary henna tattoo.
AB  - BACKGROUND: Paraphenylenediamine (PPD) is a coloring agent and potent sensitizer
      commonly added to henna tattoos to darken tattoo color. Photographic developers
      contain compounds that cross-react with PPD. Allergic contact dermatitis (ACD)
      from photo developers has been documented in the literature. OBJECTIVE: We
      describe the rare case of a photographer who presented with a 4-year history of
      recurrent ACD following exposure to photochemicals. History taking revealed that
      10 years before presentation, he had received a temporary henna tattoo. METHODS:
      The patient was patch-tested with 4-methylaminophenol sulfate (Metol), the North
      American Contact Dermatitis Group (NACDG) series, and select other allergens.
      RESULTS: Patch testing results revealed strong positive reactions to 4
      methylaminophenol sulfate and PPD. CONCLUSION: This is the first report to our
      knowledge of ACD from a photo developer occurring as a consequence of previous
      sensitization to PPD from a temporary henna tattoo. Due to the potential for long
      term sequelae, an awareness of the risks associated with henna tattoos is
      warranted.

PMID- 25775669
TI  - Polysensitization in recurrent lip dermatitis.
AB  - BACKGROUND: In allergic contact dermatitis (ACD), polysensitization consists of
      positive patch test reactions to three or more unrelated allergens. OBJECTIVE:
      The purpose of this case report is to document a 27-year-old female with
      recurrent lip dermatitis, polysensitization, and reactions to a number of
      clinically relevant exposures. METHODS: Patch testing results revealed positive
      reactions to tixocortol-21-pivalate (3+), lanolin (3+), neomycin (3+), nickel
      (1+), hydroxyethyl methylacrylate (3+), bacitracin (3+), and abitol (3+).
      RESULTS: The patient had seven positive reactions, meeting the criteria for
      polysensitization. Of known clinical relevance, the patient had applied lanolin
      containing lip balms and hydrocortisone- and bacitracin-containing products to
      the lips, all of which she was strongly reactive to on patch testing. CONCLUSION:
      Polysensitization occurs when three or more unrelated allergens are positive on
      patch testing. This case highlights the importance of considering
      polysensitization in ACD as numerous allergens that were positive on patch
      testing were clinically relevant.

PMID- 25775670
TI  - Crohn Disease of the Vulva without Gastrointestinal Manifestations in a 16-Year
      Old Girl.
AB  - BACKGROUND: Crohn disease of the vulva is a rare disease that is difficult to
      diagnose. There are limited reports describing treatment of this condition.
      OBJECTIVE: To describe the diagnosis and treatment of a 16-year-old girl with
      Crohn disease of the vulva, without onset of intestinal symptoms. METHODS: Crohn
      disease was diagnosed by histopathology. The patient was treated with
      corticosteroids and followed for 1 year. RESULTS: After the final diagnosis,
      cutaneous lesions responded rapidly to corticosteroid treatment, which was
      gradually stopped after 6 months. The disease was well controlled at the 1-year
      follow-up. CONCLUSION: Crohn disease of the vulva can develop alone without the
      onset of intestinal symptoms. Diagnosis relies on special pathologic findings.
      Corticosteroid treatment is effective for this condition.

PMID- 25775671
TI  - Periungual eccrine poroma.
AB  - BACKGROUND: Eccrine poroma is a rare, benign skin appendage tumor originating
      from the intraepidermal portion of the eccrine sweat duct, which typically occurs
      on the sides and soles of the feet. Nonetheless, eccrine poroma may be found in
      any skin area bearing sweat glands. OBJECTIVE: Herein we report a case of an
      eccrine poroma in an unusual location, the surgical management of the condition,
      and follow-up processes.

PMID- 25775673
TI  - Commentary: Treatment of in-stent restenosis in the superficial femoral artery:
      at the crossroads of using either covered stents or paclitaxel-based modalities.

PMID- 25775672
TI  - Superiority of stent-grafts for in-stent restenosis in the superficial femoral
      artery: twelve-month results from a multicenter randomized trial.
AB  - PURPOSE: To evaluate the short- and midterm outcomes of the Viabahn
      endoprosthesis with Propaten Bioactive Surface vs. standard balloon angioplasty
      for treatment of in-stent restenosis in the superficial femoral artery. METHODS:
      Between June 2010 and February 2012, 83 patients with superficial femoral artery
      in-stent and Rutherford category 2 to 5 ischemia were enrolled at 7 sites
      participating in this prospective randomized controlled study (RELINE;
      ClinicalTrials.gov; identifier NCT01108861). The patients were randomized to
      treatment with either the heparin-bonded Viabahn endoprosthesis (n = 39: 29 men;
      mean age 67.7 +/- 9.8 years) or a standard angioplasty balloon (n = 44: 32 men;
      mean age 69.0 +/- 9.7 years). The primary effectiveness outcome was primary
      patency at 12 months, defined as no restenosis/occlusion within the target lesion
      based on duplex ultrasound and no target lesion revascularization. The primary
      safety endpoint was the incidence of serious device-related adverse events within
      30 days of the procedure. RESULTS: All patients randomized to receive dilation or
      the Viabahn stent-graft were treated according to their assignment. The technical
      success was 100% for the Viabahn group and 81.8% for the angioplasty group (p =
      0.002) owing to 9 patients requiring a bailout procedure after unsuccessful
      angioplasty. The 12-month primary patency rates were 74.8% for the Viabahn group
      and 28.0% for the angioplasty group (p < 0.001). Excluding the 9 angioplasty
      patients who received bailout stenting, the primary patency for optimal balloon
      angioplasty was 37.0% (p < 0.001). Three patients experienced device-related
      adverse events within 30 days: occlusion of the target lesion (Viabahn group),
      peripheral embolization (angioplasty group), and reocclusion of the target lesion
      (angioplasty group). CONCLUSION: In this study, the treatment of femoropopliteal
      in-stent restenosis with a Viabahn endoprosthesis showed significantly better
      results than treatment with a standard balloon at 1 year.

PMID- 25775674
TI  - Paclitaxel-releasing balloon in femoropopliteal lesions using a BTHC excipient:
      twelve-month results from the BIOLUX P-I randomized trial.
AB  - PURPOSE: To evaluate the safety and efficacy of the novel Passeo-18 Lux
      paclitaxel-coated balloon compared with the Passeo-18 uncoated balloon in
      patients with symptomatic de novo or restenotic femoropopliteal lesions. METHODS:
      Sixty patients (34 men; mean age 70.7 +/- 10.1 years) in 5 European centers were
      enrolled in the BIOLUX P-I trial (ClinicalTrials.gov identifier NCT01056120) and
      randomized 1:1 to either the paclitaxel-coated balloon or the uncoated balloon.
      The primary endpoint was late lumen loss at 6 months. Secondary endpoints were
      binary restenosis at 6 months, clinically driven target lesion revascularization
      (TLR), change in ankle-brachial index and Rutherford classification, and major
      adverse events at 6 and 12 months. RESULTS: At 6 months, patients treated with
      paclitaxel-coated balloons had a significantly lower late lumen loss (0.51 +/-
      0.72 vs. 1.04 +/- 1.00 mm, p = 0.033) and binary restenosis (11.5% vs. 34.6%, p =
      0.048) than the control group. Correspondingly, clinically driven TLR was lower
      in the paclitaxel-coated balloon group at 12 months [15.4% vs. 41.7% (p = 0.064)
      for the intention-to-treat population and 16.0% vs. 52.9%, (p = 0.020) for the as
      treated population]. No death and one minor amputation were observed compared
      with two deaths and two minor amputations in the control group. No major
      amputations or thrombosis were reported. CONCLUSION: The Passeo-18 Lux paclitaxel
      coated balloon has been proven to be safe and effective in patients with
      femoropopliteal lesions, with superior performance outcomes compared with
      treatment with an uncoated balloon.

PMID- 25775676
TI  - Commentary: Future directions of superficial femoral artery stenting technology
      in the drug-coated balloon era.

PMID- 25775675
TI  - Stent placement vs. balloon angioplasty for popliteal artery treatment: two-year
      results of a prospective, multicenter, randomized trial.
AB  - PURPOSE: To investigate the 2-year technical and clinical results of primary
      nitinol stent placement in comparison with percutaneous transluminal angioplasty
      (PTA) in the treatment of de novo lesions of the popliteal artery. METHODS: The
      ETAP study (Endovascular Treatment of Atherosclerotic Popliteal Artery Lesions:
      balloon angioplasty vs. primary stenting; www.ClinicalTrials.gov identifier
      NCT00712309) is a prospective, randomized trial that enrolled 246 patients (158
      men; mean age 72 years) who were randomly assigned to receive a nitinol stent
      (n=119) or PTA (n=127) for lesions averaging 42.3 mm in length. The results of
      the primary study endpoint were published. Secondary outcome measures and
      endpoints included primary patency (freedom from duplex-detected target lesion
      restenosis), target lesion revascularization (TLR), secondary patency, changes in
      ankle-brachial index and Rutherford class, and event-free survival (freedom from
      target limb amputation, TLR, myocardial infarction, and death). RESULTS: In
      total, 183 patients (89 stent and 94 PTA) were available for the 2-year analysis.
      The primary patency rate was significantly higher in the stent group (64.2%) than
      in the PTA group (31.3%, p=0.0001). TLR rates were 22.4% and 59.5%, respectively
      (p=0.0001). When provisional stent placement in the PTA arm was not considered as
      TLR and loss in patency, the differences prevailed between the study groups but
      were not significant (64.2% vs. 56.1% for primary patency, respectively; p=0.44).
      A significant improvement in ABI and Rutherford category was observed at 2 years
      in both groups. CONCLUSION: In treatment of obstructive popliteal artery lesions,
      provisional stenting reveals equivalent patency in comparison to primary
      stenting. However, the 2-year results of this trial suggest the possibility of a
      shift toward higher patency rates in favor of primary stenting.

PMID- 25775677
TI  - Gender-related long-term outcome of primary femoropopliteal stent placement for
      peripheral artery disease.
AB  - PURPOSE: To evaluate gender-related long-term outcomes in patients undergoing
      stent treatment of femoropopliteal peripheral artery disease. METHODS: Between
      September 2006 and August 2010, all 517 patients (333 men and 184 women; mean age
      70.6 years) undergoing primary stent placement in femoropopliteal atherosclerotic
      lesions at 2 European vascular centers were prospectively enrolled in the study.
      The main study outcome was primary stent patency. Secondary outcomes included
      secondary patency, limb salvage, and all-cause mortality. RESULTS: Women had a
      higher incidence of critical limb ischemia (32.1% vs. 16.9%, p<0.001). Lesion
      characteristics according to the TransAtlantic Inter-Society Consensus (TASC)
      classification were comparable in both genders (p=0.52), although total
      occlusions and popliteal involvement were observed more frequently in female
      patients (p=0.043 and p=0.001, respectively). Both genders showed similar 5-year
      primary patency rates (64.3% men vs. 58.1% women, p=0.11). A statistically
      significant difference was observed concerning the secondary patency rates in
      favor of men (71.9% vs. 66.8% at 5 years, p=0.005). Limb salvage rates did not
      vary between the groups (p=0.83). Survival rates were comparable at 5 years
      (83.3% and 82.6% for men and women, respectively; p=0.63), although female
      patients were older at their presentation (68.5 vs. 74.3 years, p<0.001). Female
      gender was an independent risk factor for restenosis for TASC C/D lesions
      (primary patency rate 39.8% in women vs. 62.0% in men; p=0.002). Finally,
      critical limb ischemia was an independent risk factor for restenosis in women
      (odds ratio 1.5). CONCLUSION: Female gender was associated with a higher
      prevalence of critical limb ischemia, poorer secondary patency, and more frequent
      restenosis in TASC C/D lesions. Endovascular treatment of femoropopliteal lesions
      provides equal results between genders in terms of primary stent patency in the
      long term.

PMID- 25775678
TI  - Commentary: Does gender influence outcomes after femoropopliteal stenting?

PMID- 25775679
TI  - Vascular response after Zilver PTX stent implantation for superficial femoral
      artery lesions: serial optical coherence tomography findings at 6 and 12 months.
AB  - PURPOSE: To compare the vascular response after paclitaxel-coated nitinol drug
      eluting stent (Zilver PTX) implantation for superficial femoral artery lesions
      after 6 and 12 months using optical coherence tomography (OCT). METHODS: Serial
      OCT examinations were performed in 5 patients (4 men; mean age 78.4 +/- 6.8
      years) with 9 Zilver PTX stents at 6- and 12-month follow-up. Variables evaluated
      included neointimal thickness and apposition on each strut, the incidence of
      extrastent lumen (ESL), peristrut low-intensity area (PLIA), and
      neovascularization at 1-mm intervals. RESULTS: A total of 249 matched cross
      section images were evaluated and included 4788 and 4826 struts at 6 and 12
      months, respectively. Mean neointimal thickness significantly increased from 480
      to 540 um between 6 and 12 months (p < 0.001). The percentage of uncovered struts
      tended to decrease at 12 months (3% vs. 2.3%, p = 0.054), whereas the percentage
      of malapposed struts were similar at both examinations (0.2% vs. 0.2%, p > 0.99).
      Although the incidence of ESL in cross sections was not different (35% vs. 31%, p
      = 0.29), median ESL area significantly increased from 6 to 12 months [0.12 (0.04
      0.36) vs. 0.31 (0.14-0.59) mm(2), p = 0.003)]. The presence of PLIA (29% vs. 44%,
      p < 0.001) and neovascularization (14% vs. 27%, p < 0.001) increased from 6 to 12
      months. CONCLUSION: These findings suggest that delayed vascular healing and
      persistent peristent inflammation may be present even at 12 months after Zilver
      PTX implantation.

PMID- 25775680
TI  - Development and validation of a new scoring system to predict wound healing after
      endovascular therapy in critical limb ischemia with tissue loss.
AB  - PURPOSE: To develop a scoring system to predict wound healing in critical limb
      ischemia (CLI) patients treated with endovascular therapy (EVT). METHODS: Between
      July 2007 and January 2013, 184 patients (118 men; mean age 73.0 years) with CLI
      (217 limbs) and tissue loss underwent EVT. From this cohort 236 separate wounds
      were divided into development (n = 118) and validation (n = 118) groups.
      Predictors of wound healing were identified using multivariable analysis. Each
      predictor was assigned a score based on its regression coefficient, and total
      scores were calculated, ranging from 0 to 1 for low risk up to >= 4 for high risk
      of a nonhealing wound. The performance of the scoring system in the prediction of
      wound healing was evaluated by calculating the area under the receiver operating
      characteristics (ROC) curve. RESULTS: By multivariable analysis, a University of
      Texas grade >= 2 (HR 0.524, 95% CI 0.288-0.951, p = 0.034), an infected wound (HR
      0.497, 95% CI 0.276-0.894, p = 0.020), dependence on hemodialysis (HR 0.459, 95%
      CI 0.259-0.814, p = 0.008), no visible blood flow to the wound (HR 0.343, 95% CI
      0.146-0.802, p = 0.014), and major tissue loss (HR 0.322, 95% CI 0.165-0.630, p =
      0.001) predicted a non-healing wound. The 1-year rates of wound healing in the
      low-, intermediate-, and high-risk groups were 94.6%, 67.6%, and 9.1%,
      respectively, in the development group (p < 0.001) and 92.3%, 70.5%, and 31.3%,
      respectively, in the validation sample (p < 0.001). The area under the ROC curve
      was 0.922 in the development group and 0.808 in the validation sample.
      CONCLUSION: This scoring system reliably predicts wound healing in CLI patients
      after endovascular revascularization and is potentially helpful in deciding if
      additional adjuncts or revascularization should be considered.

PMID- 25775681
TI  - Pooled analysis of the CONFIRM registries: impact of gender on procedure and
      angiographic outcomes in patients undergoing orbital atherectomy for peripheral
      artery disease.
AB  - PURPOSE: To compare the acute procedure and angiographic outcomes of peripheral
      artery disease (PAD) patients treated with orbital atherectomy stratified by
      gender. METHODS: The CONFIRM I, II, and III registries are US multicenter,
      nonrandomized, all-comers registries of PAD patients who were treated with
      orbital atherectomy. All patients with gender specified in the registry database
      were included in the current analysis, which compared the final residual stenosis
      achieved after atherectomy and the rate of acute complications in female and male
      patients. The 3 registries included 3131 patients with 4761 lesions: 1261 women
      (mean age 73.2 +/- 10.7 years) with 1874 lesions and 1870 men (mean age 70.4 +/-
      10.2) with 2887 lesions. RESULTS: The women were older (p < 0.001) and had a
      higher but nonsignificant prevalence of critical limb ischemia (p = 0.075). After
      treatment, the final residual stenosis in women vs. men was 9% +/- 11% vs. 11% +/
      11%, respectively (p < 0.001). Women had a higher rate of all types of
      dissection (13.3% vs. 9.9%, p<0.001). However, both genders had similar rates of
      flow-limiting dissections (1.6% vs. 1.4%, p = 0.61), perforation, slow flow,
      vessel closure, spasm, embolism, and thrombus formation. CONCLUSION: The gender
      analysis of the CONFIRM registries revealed that there was successful lesion
      modification with orbital atherectomy in both men and women; however, women had a
      higher rate of dissection (all types). This difference is likely because of the
      older age and higher percentage of critical limb ischemia in women in this
      cohort. These results, however, suggest that additional studies should be
      completed to further understand the increased risks for women vs. men during
      endovascular procedures.

PMID- 25775682
TI  - Complications of transbrachial arterial access for peripheral endovascular
      interventions.
AB  - PURPOSE: To prospectively assess current limitations and complication rates of
      the transbrachial access technique for endovascular treatment of peripheral
      vascular pathologies. METHODS: In total, 150 patients (112 men; mean age 66.3 +/-
      10.0 years) with arterial occlusive disease underwent endovascular therapy via a
      transbrachial access. Periprocedure data (sheath size, dose area product,
      fluoroscopy time, and procedure duration) were analyzed. Postprocedure
      complications of the puncture sites were categorized as minor (local hematoma,
      pseudoaneurysm, embolization, dissection, minor bleeding) and major (thrombotic
      occlusion, hematoma requiring surgery, major bleeding, nerve injury). RESULTS:
      The minor and major complication rates were 14.0% (n = 21) and 2.7% (n = 4). The
      most frequent major complication was thrombotic occlusion of the brachial artery
      requiring surgical treatment (3/150, 2%). There was only one temporary palsy of
      the median nerve and no stroke. Local hematoma (15, 10%), pseudoaneurysm (3, 2%),
      or a combination of both (3, 2%) dominated the minor complications. The average
      dose area product and fluoroscopy time were 12,752.1 +/- 9524.5 cGy*cm(2) and
      24.3 +/- 18.4 minutes, respectively, though procedure duration was acceptable
      (121.8 +/- 48.9 minutes). CONCLUSION: Complication rates of the transbrachial
      access for endovascular treatment of peripheral or visceral artery occlusive
      disease are tolerably low, making it a safe and an important alternative to the
      transfemoral access in selected cases, though the radiation exposure is rather
      high.

PMID- 25775683
TI  - A novel technique to retrieve a maldeployed vascular closure device.
AB  - PURPOSE: To report a novel technique for endovascular retrieval of a maldeployed
      vascular closure device, obviating the need for a femoral cutdown. TECHNIQUE: To
      remove a 6-F Angio-Seal device that embolized to the superficial femoral artery,
      the contralateral common femoral artery was accessed, and an 8-F, 65-cm-long
      sheath was inserted just proximal to the embolus. A second semistiff 0.035-inch
      buddy wire was advanced past the lesion along the sheath. A 0.014-inch wire was
      advanced past the embolus, and a SpiderFX embolic protection device was deployed
      1 cm past the embolized Angio-Seal device. The sheath was advanced so as to push
      the embolus into the filter. The sheath and the filter containing the Angio-Seal
      device were then removed. CONCLUSION: Endovascular retrieval of an embolized
      Angio-Seal device can be done using an embolic filter device, restoring arterial
      flow to the limb.

PMID- 25775684
TI  - Paclitaxel-coated balloon angioplasty for symptomatic central vein restenosis in
      patients with hemodialysis fistulas.
AB  - PURPOSE: To report a retrospective observational analysis of standard balloon
      angioplasty (BA) vs. paclitaxel-coated balloon angioplasty (PCBA) for symptomatic
      central vein restenoses in patients with impaired native hemodialysis fistulas.
      METHODS: A retrospective review was conducted of 27 consecutive patients (15 men;
      mean age 66 +/- 13.8 years, range 39-90) with 32 central vein stenoses (CVS; 6
      axillary, 11 subclavian, 12 brachiocephalic, and/or 3 superior caval veins)
      treated successfully using BA. Freedom from reintervention after BA of de novo
      lesions was 7.4 +/- 7.9 months (range 1-24). Twenty-five (92.6%) patients
      developed symptomatic restenoses and were treated one or more times by BA (n =
      32) or PCBA (n = 20) using custom-made paclitaxel-coated balloons (diameter 6-14
      mm). RESULTS: Technical (< 30% residual stenosis) and clinical (functional
      fistula) success rates for the initial and secondary angioplasty procedures were
      100%. No minor/major procedure-associated complications occurred. Mean follow-up
      was 18.4 +/- 17.5 months. Kaplan-Meier analysis for freedom from target lesion
      revascularization (TLR) found PCBA superior to BA (p = 0.029). Median freedom
      from TLR after BA was 5 months; after PCBA, > 50% of patients were event-free
      during the observation period (mean freedom from TLR 10 months). Restenosis
      intervals were prolonged by PCBA (median 9 months) vs. BA (median 4 months; p =
      0.023). CONCLUSION: Paclitaxel-coated balloon angioplasty of central vein
      restenosis in patients with hemodialysis shunts yields a statistically
      significant longer freedom from TLR compared to standard balloon angioplasty.

PMID- 25775685
TI  - Percutaneous rheolytic thrombectomy of thrombosed autogenous dialysis fistulas:
      technical results, clinical outcome, and factors influencing patency.
AB  - PURPOSE: To retrospectively analyze the technical and clinical outcome of
      percutaneous rheolytic thrombectomy with the use of the AngioJet device in
      thrombosed autogenous arteriovenous dialysis fistulas. METHODS: A cohort of 38
      consecutive patients (24 men; mean age 70.7 +/- 13.8 years) presenting with 59
      thrombotic events in 39 autogenous dialysis fistulas were retrospectively
      analyzed. The AngioJet rheolytic thrombectomy device was used in all cases.
      Adjunctive therapies, as well as procedure-related complications, were noted.
      Primary, assisted primary, and secondary patency of the autogenous fistulas was
      assessed along with factors potentially influencing patency. RESULTS: Initial
      technical success to recanalize the efferent vein was 100% (n = 59), and a
      successful postprocedure dialysis session was possible in 97% (n = 57) of cases.
      Adjunctive procedures included percutaneous thromboaspiration (n = 4, 7%),
      balloon angioplasty (n = 59, 100%), and stent placement (n = 16, 27%).
      Complications related to thrombectomy occurred in 3 (5%) procedures (distal
      arterial embolus). Primary, assisted primary, and secondary patency rates at 12
      months were 56.1% (95% CI 42.8% to 75.2%), 61.6% (95% CI 48.6% to 74.7%), and
      86.2% (95% CI 74.9% to 97.5%), respectively. Risk factors for early fistula
      occlusion were greater patient age (p = 0.045), the age of the fistula (p =
      0.045), previous stent insertion (p = 0.019), and an upper arm fistula (p =
      0.047). CONCLUSION: Percutaneous rheolytic thrombectomy of autogenous dialysis
      fistulas is effective in restoring patency and allowing subsequent hemodialysis.
      The complication rate is acceptably low, and the large majority of the fistulas
      are still used for hemodialysis at 1-year follow-up. Older fistulas and upper arm
      fistulas are at higher risk for early rethrombosis.

PMID- 25775687
TI  - Commentary: Treating subacute thrombus in peripheral arterial disease: the
      effectiveness of ultrasound-accelerated lysis.

PMID- 25775686
TI  - Dutch randomized trial comparing standard catheter-directed thrombolysis and
      ultrasound-accelerated thrombolysis for arterial thromboembolic infrainguinal
      disease (DUET).
AB  - PURPOSE: To report the results of the Dutch randomized trial comparing standard
      catheter-directed and ultrasound-accelerated thrombolysis (UST) for the treatment
      of arterial thromboembolic occlusions. METHODS: The DUET study ( controlled
      trials.com ; identifier ISRCTN72676102) was designed to assess whether UST can
      reduce therapy time significantly compared with standard thrombolysis (ST). Sixty
      patients (44 men; mean age 64 years) with recently (7-49 days) thrombosed
      infrainguinal native arteries or bypass grafts causing acute limb ischemia
      (Rutherford category I or IIa) were randomized to ST (n = 32) or UST (n = 28).
      The primary outcome was the duration of thrombolysis needed for uninterrupted
      flow (> 95% thrombus lysis), with outflow through at least 1 below-the-knee
      artery. Continuous data are presented as means +/- standard deviations. RESULTS:
      Thrombolysis was significantly faster in the UST group (17.7 +/- 2.0 hours) than
      in the ST group (29.5 +/- 3.2 hours, p = 0.009) and required significantly fewer
      units of urokinase (2.8 +/- 1.6 * 10(6) IU in the ST group vs. 1.8 +/- 1.0 *
      10(6) IU in the UST group, p = 0.01) for uninterrupted flow. Technical success
      was achieved in 27 (84%) patients in the ST group vs. 21 (75%) patients in the
      UST group (p = 0.52). The combined 30-day death and severe adverse event rate was
      19% in the ST group and 29% in the UST group (p = 0.54). The 30-day patency rate
      was 82% in the ST group as compared with 71% in the UST group (p = 0.35).
      CONCLUSION: Thrombolysis time was significantly reduced by UST as compared with
      ST in patients with recently thrombosed infrainguinal native arteries or bypass
      grafts.

PMID- 25775688
TI  - Pharmacomechanical thrombolysis in the management of acute inferior vena cava
      filter occlusion using the Trellis-8 device.
AB  - PURPOSE: To evaluate the performance and safety of the Trellis-8 system, a
      pharmacomechanical thrombolysis infusion catheter, and adjunctive therapies in
      the treatment of symptomatic inferior vena cava (IVC) filter-related acute
      thrombotic occlusion. METHODS: Eight consecutive patients (6 men; mean age 57.4
      years, range 34-78 years) with acute thrombotic occlusion of the IVC in the
      presence of an IVC filter underwent percutaneous venous thrombectomy using the
      Trellis-8 thrombectomy system and adjunctive techniques between January 2009 and
      November 2013. Demographics, clinical data, procedures, and outcomes were
      retrospectively reviewed. All patients had clinical signs of lower extremity
      venous hypertension on presentation. The median time between IVC filter placement
      and occlusion was 25 months. Patients were followed for the development of
      thromboembolic complications to the last clinic visit or until they died.
      RESULTS: The procedure was technically successful in 6 patients, whereas it could
      not be performed in 2 due to failure to cross the occlusion. The median follow-up
      period was 7.8 months, at which time all patients undergoing successful Trellis-8
      thrombectomy had relief of symptoms without thromboembolic or bleeding
      complications. CONCLUSION: In this limited performance and safety evaluation, the
      Trellis-8 thrombectomy system combined with adjunctive therapies, such as
      mechanical thrombectomy and balloon angioplasty, was effective in 75% of patients
      with IVC filter-related acute caval occlusion.

PMID- 25775689
TI  - Impact of renal chimney grafts on anatomical suitability for endovascular repair
      in ruptured abdominal aortic aneurysm.
AB  - PURPOSE: To evaluate the impact of renal chimney grafts on anatomical suitability
      for endovascular aneurysm repair (EVAR) in ruptured abdominal aortic aneurysm
      (rAAA). METHODS: Contrast-enhanced computed tomography images of 206 patients
      with rAAA [175 men (mean age 75 +/- 7.8 years) and 31 women (mean age of 76 +/-
      7.5 years)] were evaluated in a dedicated 3-dimensional vascular workstation.
      Assessment of infrarenal EVAR suitability was based on predefined anatomical
      variables reflecting the Instructions for Use of commercially available stent
      grafts. In patients where aneurysm neck length was the only limiting factor for
      suitability, reevaluation of the proximal sealing zone was done, accounting for
      chimney grafts in one or both renal arteries. RESULTS: Seventy (34%) rAAA
      patients were anatomically suitable for EVAR: 65 (37%) of 175 men and 5 (16%) of
      31 women (p < 0.01). Eighty-nine (65%) of the 136 unsuitable patients had
      aneurysm necks < 15 mm long; short neck was the only exclusion criterion in 33
      (24%) cases. In the 33 short-necked aneurysms without other limiting factors, a
      proximal sealing zone > 15 mm could potentially be achieved with one or two renal
      chimney grafts in 12 (36%) and 25 (76%) patients, respectively, increasing
      overall suitability to 40% and 46%. If access issues could also be solved and a
      similar strategy with chimneys for the renal arteries was applied, the EVAR
      suitability would increase further to 58%. CONCLUSION: Roughly one third of
      patients with rAAA are anatomically suitable for EVAR; short aneurysm neck is the
      most common exclusion criteria. In appropriate cases, chimney grafts in one or
      both renal arteries may increase overall suitability by 12%. Suitability
      increases to ~ 60% when iliac access issues are additionally overcome.

PMID- 25775690
TI  - Infective etiology affects outcomes of late open conversion after failed
      endovascular aneurysm repair.
AB  - PURPOSE: To retrospectively review all patients undergoing late open conversion
      (LOC) after endovascular aneurysm repair (EVAR) in order to identify any clinical
      or technical predictors of poor outcome. METHODS: Twenty-six consecutive patients
      (24 men; mean age 74.7 +/- 8.3 years) underwent LOC between June 2006 and April
      2013 at our institution. The mean interval from index EVAR to LOC was 40.4 +/-
      29.2 months (range 5-93 months). The indication for LOC was endoleak in 14 (54%)
      patients and infection in 12 (46%): 2 (8%) patients with endoleak had a ruptured
      aneurysm and 6 (23%) patients with infection had a recurrent secondary
      aortoesophageal fistula (sAEF). RESULTS: In all 12 cases of infection and in 12
      of 14 endoleaks, the entire endograft was explanted. A rifampin-soaked Dacron
      silver graft was implanted in all patients with infection. Patients with any
      infection and with recurrent AEF required more blood units than patients with
      endoleak (6.40 vs. 1.86, p = 0.045; 6.76 vs. 1.86, p = 0.0036, respectively).
      Compared with endoleak, the duration of conversions in the setting of infection
      (274 vs. 316 minutes, p = 0.42) and recurrent sAEF (274 vs. 396 minutes, p =
      0.021) was longer. All patients with recurrent sAEF died at a mean 3.0 +/- 2.5
      days after LOC from proximal anastomosis disruption and hemorrhagic shock (n =
      2), myocardial infarction (n = 2), acute stroke (n = 1), or persistent sepsis (n
      = 1). Perioperative mortality was significantly higher in patients with endograft
      infection (6/12, p = 0.002) and in cases of supraceliac cross-clamping (4/6, p =
      0.003). The association of infection with supraceliac cross-clamping was a strong
      predictor for perioperative mortality (p < 0.001). CONCLUSION: In our experience,
      endograft infection led to greater perioperative mortality after LOC. Recurrent
      aortoenteric fistula in association with supraceliac cross-clamping is a strong
      predictor of poor outcome. Patients surviving the perioperative period may have
      good chances of long-term survival.

PMID- 25775691
TI  - Radiofrequency in situ fenestration for aortic arch vessels during thoracic
      endovascular repair.
AB  - PURPOSE: To report the first clinical application of a novel technique using
      radiofrequency puncture to create retrograde in situ fenestrations during
      thoracic endovascular aortic repair (TEVAR). METHODS: Between June 2011 and
      December 2013, 40 TEVAR procedures were performed in our facility, including 10
      cases in which in situ fenestration was planned. Two thoracic stent-graft models
      were deployed: the Valiant (n=5) and the Zenith TX2 (n=5). A 0.035-inch PowerWire
      radiofrequency guidewire delivered from a brachial approach was used to
      fenestrate the grafts covering a left subclavian artery (LSA) in 9 cases and a
      left common carotid artery in one. The fenestrations were serially dilated to 6
      mm, and self-expanding Advanta V12 covered stents were positioned in the target
      arteries. RESULTS: Technical success was achieved in 6 of the 10 planned cases.
      Of the remaining 4 cases, stent-grafts were deployed in zone 3 in 2 cases (one
      received a chimney to the LSA). Another stent-graft was deployed in zone 2
      without endoleak after fenestration was abandoned (the LSA had good filling via
      the vertebral artery). In the last case, the fenestration was unsuccessful in
      double-layered (proximal extension overlap) stent-grafts; a carotid-axillary
      bypass was required. There were no fenestration-related complications, but
      overall surgical complications included a case of paraparesis that resolved
      following spinal drainage and a death from a preexisting aortoesophageal fistula.
      There were no postoperative strokes. All fenestrations remained patent, and there
      were no endoleaks at a mean 12-month follow-up (range 1-33). CONCLUSION:
      Radiofrequency puncture is a viable alternative to needle or laser punctures for
      in situ fenestration during TEVAR. Early clinical results suggest technical
      feasibility and acceptable early outcomes.

PMID- 25775692
TI  - Role of stent selection in the incidence of persisting hemodynamic depression
      after carotid artery stenting.
AB  - PURPOSE: To investigate the possible role of stent selection and procedure
      related vessel diameter changes in the development of persisting hemodynamic
      depression (PHD) and to demonstrate the effectiveness and safety of permanent
      pacemaker implantation in patients with refractory PHD. METHODS: Data from 584
      procedures performed in 542 patients (398 men; mean age 67.3 years) between 2008
      and 2011 using Wallstent, Precise, and Xact stents in a nonrandomized fashion
      were analyzed retrospectively. Cardiovascular risk factors and lesion, stent, and
      balloon characteristics were collected, and the pre- and postprocedure diameters
      of the common carotid artery (CCA) and internal carotid artery were measured. PHD
      was defined as any episode of hypotension (systolic blood pressure <90 mm Hg)
      and/or bradycardia (heart rate <60/min) lasting >6 hours. Risk factors for PHD
      were sought using logistic regression analyses; the results are presented as the
      odds ratio (OR) and 95% confidence interval (CI). RESULTS: The incidence of PHD
      was 37.0% (216/584). Refractory PHD was encountered in 9 patients; among these, 6
      were successfully treated with pacemaker implantation. A history of prior
      ipsilateral carotid endarterectomy (OR 0.44, 95% CI 0.22 to 0.87, p=0.019) and
      the presence of a contralateral high-grade stenosis (OR 0.12, 95% CI 0.02 to
      0.95, p=0.045) were independent protective factors, while calcification (OR 1.5,
      95% CI 1.03 to 2.18, p=0.034), involvement of the carotid bulb (OR 2.56, 95% 1.62
      to 4.03, p<0.001), and implantation of a nitinol stent (adjusted OR 1.62, 95% CI
      1.12 to 2.34, p=0.011) were independent risk factors for developing PHD after
      carotid artery stenting. The ratio of the post-/preprocedure CCA diameter
      (p=0.002), the stent to CCA diameter ratio (p=0.009), and the presence of
      residual stenosis (p=0.009) were significantly higher in the PHD group.
      CONCLUSION: Stent selection and procedure-related changes in vessel diameter may
      have an influence on the development of PHD. Permanent pacemaker implantation is
      an effective treatment option in patients with refractory PHD.

PMID- 25775693
TI  - Bare metal stents for treatment of extracranial internal carotid artery
      aneurysms: long-term results.
AB  - PURPOSE: To examine the long-term outcomes of bare metal stent placement for
      exclusion of extracranial internal carotid artery (ICA) aneurysms. METHODS: From
      2006 to 2011, 7 consecutive symptomatic patients (4 men; mean age 52 years) with
      surgically inaccessible extracranial ICA aneurysms were treated with a bare stent
      at a single center. Patients received clopidogrel for 3 months after the
      procedure and aspirin for life. Clinical follow-up with duplex ultrasound and/or
      computed tomographic angiography was performed at 3, 6, and 12 months and yearly
      thereafter. RESULTS: All procedures were technically successful; no neurological
      complications occurred. After 6 months, there was complete thrombosis of the
      aneurysm in all except one case. In this asymptomatic patient, the residual
      active flow was successfully obliterated by additional coil embolization. Over a
      mean follow-up of 57 +/- 22 months, all patients were alive and free of local or
      central neurological symptoms. All stents were patent, and thrombosis of the
      aneurysms was complete. CONCLUSION: In this small series, treatment of
      extracranial ICA aneurysms with a bare stent seems technically feasible and safe.
      All treated extracranial ICA aneurysms were excluded by primary intervention or
      secondary coil embolization.

PMID- 25775694
TI  - Direct percutaneous carotid access for carotid angioplasty and stenting.
AB  - PURPOSE: To describe a direct percutaneous carotid access technique for carotid
      artery stenting (CAS) that circumvents the potential for embolization that can
      occur during catheter manipulation in the aortic arch during femoral access.
      TECHNIQUE: After inducing anesthesia, an ultrasound transducer is placed at the
      base of the neck above the clavicle. A 21-G, 7-cm needle from a micropuncture
      introducer is used for single-wall puncture of the common carotid artery (CCA). A
      0.018-inch guidewire is inserted into the needle for placement of a 4-F, 10-cm
      introducer. After placing a 0.035-inch angled guidewire in the external carotid
      artery, the 4-F introducer is exchanged for the closure device sheath (preclose
      technique). A regular 6-F introducer is then placed inside the closure device
      sheath, and a low dose (2000 units) of heparin is administered for the brief CAS
      procedure, which is performed under cerebral protection. After a successful
      procedure is confirmed, the protection device is retrieved, and the closure
      device is applied to seal the puncture. CONCLUSION: This approach has a low rate
      of neurological and access site complications. Percutaneous direct carotid access
      could extend the indications for CAS to include difficult anatomies, high-risk
      patients, and certain emergent situations that warrant easy and rapid access to
      the CCA.

PMID- 25775695
TI  - New horizons in aortic disease: the lasting legacy of a visionary innovator.

PMID- 25775696
TI  - Re: Distal macro- and microembolization during subintimal recanalization of
      femoropopliteal chronic total occlusions.

PMID- 25775702
TI  - Congenital anomalies involving the coronary sinus.
AB  - A classification is presented of anomalies involving the coronary sinus. These
      anomalies are classified into four anatomic groups on the basis of (1)
      enlargement of the coronary sinus, (2) absence of the coronary sinus, (3) atresia
      of the right atrial coronary sinus ostium, and (4) hypoplasia of the coronary
      sinus. Anomalies involving the coronary sinus often are associated with other
      venous anomalies, either of the systemic or the pulmonary circulation. In some
      there is no basic disturbance of the circulation. Those conditions involving the
      coronary sinus which are of major functional significance participate in shunts,
      either left-to-right or right-to-left in nature. Enlargement of the coronary
      sinus in the absence of a shunt usually indicates that a systemic venous channel
      joins the coronary sinus anomalously.

PMID- 25775703
TI  - Pharmaceuticals and medical devices: FDA oversight.

PMID- 25775704
TI  - Pharmaceuticals and medical devices: medical devices.

PMID- 25775705
TI  - Healthcare reform: enforcement and compliance.

PMID- 25775706
TI  - Healthcare reform: administrative rulemaking.

PMID- 25775707
TI  - Healthcare reform: delivery reform.

PMID- 25775708
TI  - Healthcare reform: insurance market reform.

PMID- 25775709
TI  - Healthcare reform: payment reform.

PMID- 25775710
TI  - Healthcare reform: state specific responses.

PMID- 25775711
TI  - Healthcare facilities.

PMID- 25775712
TI  - Healthcare information technology.

PMID- 25775713
TI  - Medical errors and patient safety: reducing medical errors and improving patient
      safety.

PMID- 25775714
TI  - Medical malpractice and tort reform.

PMID- 25775715
TI  - Emergency care.

PMID- 25775716
TI  - Healthcare workforce.

PMID- 25775717
TI  - Quality of healthcare.

PMID- 25775718
TI  - Long-term care: end-of-life issues.

PMID- 25775719
TI  - Long-term care: funding of long-term care.

PMID- 25775720
TI  - Long-term care: home- and community-based services.

PMID- 25775721
TI  - Long-term care: facility quality and safety.

PMID- 25775722
TI  - Access to health insurance.

PMID- 25775723
TI  - Access to health insurance: State Children's Health Insurance Program.

PMID- 25775724
TI  - Identifying factors that influence the length of stay in patients with Non-ST
      segment elevation acute coronary syndrome in Siriraj Hospital.
AB  - OBJECTIVE: Acute coronary syndrome is a leading cause of hospitalization from
      cardiac disease. The Siriraj NSTE-ACS registry was developed in 2012 as a single
      center registry. This study purpose is to identify factors affecting the length
      of stay of the patients in the registry. MATERIAL AND METHOD: From January 2012
      to March 2013, 130 patients were enrolled consecutively. The patients were
      classified into two groups; patients with length of stay > 5 days, and a group of
      patients with length of stay <= 5 days. Comparison of variables of interest among
      the patient groups was performed using appropriate statistic RESULTS: There were
      130 patients in the study. Males were predominate (56.9%). More than 80% of the
      patients were classified as high-risk based on TIMI risk score >= 3. Most
      patients (64.6%) had LOS > 5 days. Among various variables, coronary angiogram
      during admission, heart failure at presentation, and GRACE risk score > 130 were
      associated with LOS > 5 days with the odds ratio of 4.05, 4.34, and 3.23,
      respectively. Reimbursement policy also had impact on LOS. Using universal
      coverage as a reference, odds ratio for LOS > 5 days for government paid policy
      and selfpaid/private insurance policy were 0.28 and 0.05, respectively.
      CONCLUSION: Factors affecting LOS include CAG during admission, reimbursement
      policy, heart failure at presentation, and the GRACE risk score > 130. Heart
      failure at presentation had highest impact on length of stay with an adjusted
      odds ratio of 4.34.

PMID- 25775725
TI  - Prevalence and echocardiographic characteristics of common congenital heart
      disease in adult patients at Siriraj Hospital: 10-year study.
AB  - BACKGROUND: The number of adult patients with congenital heart disease (CHD) has
      increased rapidly and represents a major challenge in cardiovascular medicine.
      Data regarding the prevalence and characteristics of adult CHD in Thai population
      over the past decade are lacking. MATERIAL AND METHOD: Patients who underwent
      comprehensive transthoracic echocardiographic study at Siriraj Hospital during
      January 2003 to May 2013 with the diagnosis of unrepaired CHD and complete data
      were enrolled in the study Patients with uncertain diagnosis, prior cardiac
      intervention, bicuspid aortic valve, patent foramen ovale, mitral valve prolapse,
      isolated persistent left superior vena cava and congenital cardiomyopathies were
      excluded. RESULTS: Among 27,132 patients underwent transthoracic
      echocardiography, 1,082 (age 36.7 +/- 14.7 years, 75.3%female) had the diagnosis
      of CHD and the prevalence was 4.0% (95% confidence interval = 3.76-4.23%). The
      majority were isolated simple left-to-right shunt lesions: atrial septal defect
      (43%), ventricular septal defect (27%) and patent ductus arteriosus (11%).
      Eisenmenger syndrome was reported in 77 patients (age 39.1 +/- 10.8 years, 71.4%
      female). Pulmonic stenosis and Ebstein's anomaly were reported in 2.9% and 2.8%
      of patients, respectively. Tetralogy of Fallot was the most common cyanotic
      defect (3.5%). The combinations of shunts and/or right-sided obstructive lesions
      were reported in 4.8%. CONCLUSION: The prevalence of adult CHD diagnosed by
      echocardiography at Siriraj Hospital was 4.0% and atrial septal defect was the
      most common form. Simple shunt lesions represent more than 80% of patients.
      Female predominance was reported in all common forms of CHD. Echocardiography is
      fundamental for the diagnosis and management of patients with CHD.

PMID- 25775726
TI  - Prevalence and predictors of appropriate implantable cardioverter defibrillator
      therapy in chronic left ventricular dysfunction patients for primary prevention
      of sudden cardiac death in Siriraj Hospital.
AB  - OBJECTIVE: The purpose of the present study was to identify the prevalence and
      predictors offirst appropriate implantable cardioverter defibrillator (ICD)
      therapy in patients with chronic LV dysfunction after placement of lCD for
      primary prevention. MATERIAL AND METHOD: Retrospective design was used. Patients
      (n = 115) from Siriraj Hospitals with ischemic or non-ischemic cardiomyopathy who
      underwent ICD implantation for primary prevention were studied. Clinical data and
      ICD therapy data were obtained from medical records and lCD interrogation
      reports. RESULTS: First appropriate ICD therapy for ventricular tachycardia (VT)
      or ventricular fibrillation (VF) were seen in 22 patients (19%) of whom 11 (9.5%)
      received lCD shock and 11 patients (9.5%) received anti-tachycardic pacing. Lack
      of beta-blocker use and lack ofaldosterone antagonist use were identified as
      significant predictors of appropriate therapy. There was no difference in
      prevalence of appropriate ICD therapy between ischemic and non-ischemic groups.
      The freedom from first appropriate therapy at 1, 2 and 3 years was 88%, 80% and
      78%. The freedom rate was constant after the third year CONCLUSION: Nearly one
      fifth of chronic LV dysfunction patients with primary prevention ICD implantation
      experience appropriate ICD therapy. Most first appropriate ICD therapy occurs
      within 2 years after implantation. Lack ofbeta-blocker use and lack of
      aldosterone antagonist use were significant predictors of appropriate therapy.

PMID- 25775727
TI  - Switching from high-efficacy lipid-lowering therapies [atorvastatin or
      rosuvastatin] to simvastatin and the results on low-density lipoprotein
      cholesterol level.
AB  - BACKGROUND: In Thai National List of Essential Drugs in 2010, simvastatin is the
      only medication on the list for the statin group. Patients who previously
      prescribed other groups of statin were recommended to switch to simvastatin.
      OBJECTIVE: Comparison of lipid low-density lipoprotein cholesterol (LDL) levels
      before and after switching from rosuvastatin or atorvastatin to simvastatin.
      MATERIAL AND METHOD: The study was a retrospective observational study performed
      in patients older than 18 year-old who were enrolled as an outpatient at Siriraj
      Hospital during October 2009 and October 2010. From these patients who were
      switched from atorvastatin or rosuvastatin to simvastatin, LDL level was compared
      between before and after switching to simvastatin. RESULTS: Of 276 patients who
      were switched from atorvastatin to equivalent dose simvastatin, LDL levels
      increased from 106.20 +/- 33.47 mg/dl to 109.61 +/- 39.62 mg/dl (p = 0.089). Of
      228 patients who were switched from rosuvastatin to a less than equivalent dose
      simvastatin, LDL levels increased from 112.73 +/- 45.94 mg/dl to 114.49 +/- 42.70
      mg/dl (p = 0.437). CONCLUSION: In the patients who were switched from
      atorvastatin and rosuvastatin to simvastatin, LDL levels before and after being
      switched was not significantly different. Moreover patients who had switched from
      rosuvastatin to a less than equivalent dose ofsimvastatin still had no
      significant increases in LDL levels after switching.

PMID- 25775728
TI  - Association between the severity of knee osteoarthritis and serum cartilage
      biomarker levels.
AB  - BACKGROUND: Osteoarthritis (OA) is the most common form of arthritis. However,
      there has been no cost-effective tool for the investigation of the severity and
      progression of the disease because using OA standard diagnostic methods causes
      cartilage damage. OBJECTIVE: To evaluate the relationship between serum
      chondroitinsulphate WF6 (CS-WF6) and hyaluronate (HA) and the severity of knee OA
      according to Kellgren-Lawrence (K/L) grades of radiographic severity and minimal
      joint space width (JSWV). MATERIAL AND METHOD: One-hundred and twenty-six
      patients with OA (knee) according to K/L grades were classified into four groups.
      The JSW of the tibiofemoraljoint were measured from standing PA radiographs.
      Serum CS-WF6 and HA were analyzed by the ELISA based technique. One-way analysis
      of variance, Bonferroni's method and Kendall's tau coefficient relation test were
      performed to evaluate the association of K/L grades and JSW with levels of CS-WF6
      and HA, respectively. RESULTS: Serum CS-WF6 levels in grade 4 were significantly
      increased when compared with the other grades (p < 0.05). The serum HA level did
      not show any significant difference among the grades of severity. The serum CS
      WF6 level showed a significant negative correlation with the JSW and its levels
      rose rapidly to the level beyond 300 ng/ml. There was no correlation found
      between the levels of serum HA and JSW CONCLUSION: WF6 levels may be useful in
      identifying patients at risk of rapid progression reflected by a point of an
      abruptly high WF6 level. The determination of WF6 in the serum showed increasing
      levels in more severe grades, so it could be useful in monitoring the
      effectiveness of treatment. There were some limitations because of broad
      distribution and overlap with the normal range. Thus, it may not be suitable as a
      diagnostic tool.

PMID- 25775729
TI  - Cervical spinal tuberculosis: a preliminary study of clinical diagnosis and
      management.
AB  - BACKGROUND: Cervical involvement in spinal tuberculosis is rare; however delayed
      diagnosis and treatment may result in massive, irreversible neurological
      deterioration. The purpose of this study is to report on a strategy for clinical
      diagnosis and management of cervical spinal tuberculosis. MATERIAL AND METHOD:
      Eighteen patients (13 males and 5 females) during 1998-2013 were retrospectively
      reviewed at Chiang Mai University Hospital. The patients had a mean age of 51.4
      years (range 37-68 years). History, examination, radiographs, MRI and tissue
      sampling were used in diagnosis. Most of the patients were given antituberculous
      therapy (ATT) and underwent surgical management. The mean follow-up period was
      12.8 months. RESULTS: Axial neckpain, quadriparesis, spastic gait and hand
      clumsiness were the predominant symptoms. Disc narrowing, endplate destruction
      andparaspinal soft tissue swelling were the prominent radiographic findings. MRI
      found Gadolinium enhancement of prevertebral soft tissue, T2 hypersignal of the
      intervertebral discs, intraosseous T2 hypersignal at the vertebral body, and disc
      fragmentation. Thirteen patients underwent single-stage anterior debridement with
      fusion. Three patients underwent posterior fusion alone. Axial neck pain improved
      in all patients. Nurick's disability index and fusion rate improved in 70% of the
      patients after conservative and surgical treatment. CONCLUSION: Cervical spinal
      tuberculosis should be suspected in endemic patients with severe neck pain and
      progressive neurological deficit. Histopathology is the gold standard of
      tuberculosis diagnosis. Anti-tuberculosis drugs should be continued for at least
      12 months. Radical anterior debridement and instrumented fusion has demonstrated
      favorable results. The posterior approach is an alternative treatment in patients
      when the anterior approach cannot be performed or as part of second-stage
      surgery.

PMID- 25775730
TI  - Correlation of proximal femoral bone geometry from plain radiographs and dual
      energy X-ray absorptiometry in elderly patients.
AB  - BACKGROUND: Fracture prevention in osteoporotic patients is the primary treatment
      goal in assessing bone mineral density, identification of fracture risk, and
      determination of who should be treated. The literature shows that parameters of
      proximal femoral bone geometry such as hip axis length, femoral neck shaft angle
      (FNA), femoral neck width (FNW) and femoral neck cortical thickness (FNCT) can
      predict the risk of hip fracture. Those parameters are presented automatically
      with dual energy X-ray absorptiometry (DXA) scans, which are available in well
      equipped hospitals. OBJECTIVE: To determine the correlation between proximal
      femoral bone geometry and the parameters from DXA scans and those from plain
      radiographs. MATERIAL AND METHOD: Forty-eight patients with no previous hip
      fractures or history of secondary osteoporosis underwent both a DXA scan of the
      hip area and a plain hip radiograph done in the same position, 25 degrees
      internal rotation. Bone geometries from both groups were measured to determine
      the correlation using Pearson correlation coefficient. RESULTS: Correlation
      between the parameters HAL, FNA, FNW andFNCT from the DXA scans and from the
      measurement of the plain radiograph was significant (p < 0.01) and the level of
      correlation was moderate to high. The FNCT had least mean difference (0.04). In
      addition, the parameter FNCT less than 0.29 mm in both DXA scans and plain
      radiographs, showed a significant correlation with osteoporosis (T-score <-2.5).
      CONCLUSION: The bone geometry parameters from either DXA scans orplain
      radiographs may be used to predict osteoporotic hip fracture with a moderate to
      high correlation. Plain radiographs are very helpful when DXA scan results are
      not available. The FNCT parameter has a strong correlation with osteoporosis.

PMID- 25775731
TI  - Diurnal variation of serum chondroitin sulfate WF6 and hyaluronic acid in the
      healthy, traumatic knee and the osteoarthritic knee.
AB  - OBJECTIVE: An understanding of diurnal change is one of the important milestones
      for either biomarker validation or therapeutic level monitoring. The present
      study determines the most suitable period during the day for serum chondroitin
      sulfate WF6 (CS-WF6) and hyaluronic acid (HA) collection, and identifies the
      possible factors which affect the estimated putative half-life of serum CS-WF6
      and hyaluronic acid (HA). MATERIAL AND METHOD: Forty-nine volunteers were
      enrolled in the present study, 22 healthy, 14 with anterior cruciate ligament
      (ACL) injury, and 13 volunteers with osteoarthritis (OA). Blood sample collection
      was carried out every four hours starting at 18.00 hours for 24 hours, with
      additional samples taken at 07:00 and 08:00 hours. Serum CS-WF6, HA levels were
      determined by an ELISA-based assay. RESULTS: The serum CS-WF6 level was
      significantly different between the normal and both pathological conditions. The
      serum HA level was significantly different in every condition. There was no
      diurnal pattern of serum CS-WF6 and HA during the 24 hour period. An estimated
      putative half-life of serum CS-WF6 and HA was 4.32 +/- 2.63 and 4.10 +/- 2.34,
      respectively. The maximum CS-WF6, creatinine clearance (CrCl) level and body mass
      index (BMI) were not related to the changes of the WF6 half-life. The higher
      maximum HA and CrCl level related to the longer half-life of serum HA level, p =
      0.008 and p = 0.001, respectively. CONCLUSION: There was no diurnal pattern of
      serum CS-WF6 and HA due to the present study approach. Two hours after awakening
      in official time would be the suitable for serum CS-WF6. Two hours after
      awakening and after meals were suitable times for serum HA collection.

PMID- 25775732
TI  - Effectiveness of Mom-made Pavlik harness for maintaining reduction of the hip in
      DDH.
AB  - BACKGROUND: Co-operation of the parent is a major factor for successful treatment
      of developmental dysplasia of the hip (DDH). The commercial Pavlik harness is too
      expensive and the parent may not understand or refuse its use. Regarding the
      function of the Pavlik harness and awareness of complications, a Mom-made Pavlik
      harness was developed. OBJECTIVE: To evaluate the effectiveness of Mom-made
      Pavlik harness in maintaining the reduction ofDDH MATERIAL AND METHOD: Infants
      with Ortolani positive DDH, ages up to five months, treated at Maharat Nakhon
      Ratchasima Hospital between October 2003 and September 2012, were analyzed,
      retrospectively. Irreducible DDH, neuromuscular DDH and hyperlaxity syndrome were
      excluded. A Mom-made Pavlik harness was used to maintain reduction after the
      initial two weeks of a hip spica cast. The success of treatment was evaluated by
      ultrasound of the hip. The center edge (CE) angle was measured from AP film at
      age one and four years. RESULTS: There were 24 infants, 35 hips with 11
      bilateral, seven left and six right sides DDH. Thirty-two hips were successfully
      reduced (91.4%). Three hips had recurrent dislocation. Two of these were further
      managed by adductor tenotomy and closed reduction under general anesthesia and
      hip spica cast, followed by hip abduction brace. Another was treated by open
      reduction and Salter's innominate osteotomy. The average CE angle at age one and
      four years was 16.5 and 25.9 degree, respectively. CONCLUSION: Treatment of the
      infants with DDH requires a long period of care not only in hospital but also at
      home. Therefore, it needs the diligence, intention and regularity by their
      parents to achieve a successful outcome. The Mom-made Pavlik harness represents
      the spirit of this resolution.

PMID- 25775733
TI  - Factors related to mortality after osteoporotic hip fracture treatment at Chiang
      Mai University Hospital, Thailand, during 2006 and 2007.
AB  - OBJECTIVE: To investigate the one-year mortality rate after osteoporotic hip
      fracture and to identify factors associated with that mortality rate. MATERIAL
      AND METHOD: A retrospective review of 275 osteoporotic patients who sustained a
      low-trauma hip fracture and were admitted in Chiang Mai University Hospital
      during January 1, 2006 to December 31, 2007 was accomplished. Eligibility
      criteria were defined as age over 50 years, fracture caused by a simple fall and
      not apathologicalfracture caused by cancer or infection. Results of this one-year
      mortality rate study were compared to studies of hip fracture patient mortality
      in 1997 and the period 1998-2003. RESULTS: The average one-year mortality rate in
      2006-2007 was 21.1%. Factors correlated with higher mortality were non-operative
      treatment, delayed surgical treatment, and absence of medical treatment for
      osteoporosis. The 2006-2007 mortality rate was slightly higher than for the 1997
      and 1998-2003 periods. CONCLUSION: The one-year mortality rate after osteoporotic
      hip fracture of 21.1% was approximately 9.3 times the mortality rate for the same
      age group in the general population, indicating that treatment of osteoporosis as
      a means of helping prevent hip fracture is very important for the individual, the
      family, and society as a whole.

PMID- 25775734
TI  - Foot and ankle problems in Muay Thai kickboxers.
AB  - BACKGROUND: Muay Thai kickboxing is a common sport that uses the foot and ankle
      in fighting. Muay Thai kickboxing trainees usually receive training in Thailand
      Foot and ankle problems in this group ofpeople who usually train barefoot remain
      unexplored OBJECTIVE: To evaluate the prevalence of common foot and ankle
      problems in Muay Thai kick boxers. MATERIAL AND METHOD: The present study is a
      cross-sectional survey of Muay Thai kick boxers practicing in northern Thailand.
      Interviews were conducted and foot and ankle examinations were evaluated Foot
      morphology was examined using a Harris mat footprint. RESULTS: One hundred and
      twenty-three Muay Thai kickbox ersinnine training gyms were included in this
      study. Common foot and ankle problems found in the Muay Thai kick boxers were
      callosity (59%), gastrocnemius contracture (57%), toe deformities (49.3%), wounds
      (10%) and heel pain (9%). Callosity was most commonly found on the forefoot
      (77.5%), on the plantar first metatarsal (55.3%) and on the big toe (33.3%). An
      association was found between a tight heel cord and a history of foot injury with
      prolonged periods of weekly training. Toe deformities such as hallux rigidus
      (37.6%) were also associated with prolonged periods of training (p = 0.001). No
      correlation was found between type of foot arch and foot and ankle problems.
      CONCLUSION: Plantar forefoot callosities and wounds as well as toe deformities
      including tight heel cords are some of the foot and ankle problems commonly found
      in Muay Thai kick boxers. They are associated with prolonged periods of barefoot
      training. The unique pattern of training and of the kicks in Muay Thai might be a
      path mechanism, leading to the development of foot and ankle problems.

PMID- 25775735
TI  - Foot and ankle problems in Thai monks.
AB  - BACKGROUND: Foot and ankle problems in Thai monks have not been explored. This is
      an unshod population, and its members have a unique lifestyle living among others
      in our modern era. Beginning at their ordainment, they follow strict rules about
      barefoot walking, the amount of daily walking, and their sitting position,
      practices that theoretically can increase their risk of developing foot and ankle
      problems. OBJECTIVE: To evaluate the prevalence ofcommon foot and ankle problems
      in Thai monks. MATERIAL AND METHOD: A cross-sectional survey was conducted in
      combination with foot and ankle examinations of monks living in northern Thailand
      Foot morphology was examined using a Harris mat footprint. Results of the
      interviews and the foot and ankle examinations were evaluated. RESULTS: Two
      hundred and nine monks from 28 temples were included in this study. Common foot
      and ankle problems found included callosity (70.8%), toe deformities (18.2%),
      plantar fasciitis (13.4%), metatarsalgia (3.8%), and numbness (2.9%). Callosity
      and toe deformities were associated with prolonged barefoot walking over extended
      periods since ordainment (p < 0.05). The callosity was found on the forefoot
      (47.3%), lateral malleolus (40.7%), and heel (12%). Arch types were considered
      normal in 66.4% of cases, high in 21.6%, and low in 12%. No association was found
      between arch type and foot and ankle problems. CONCLUSION: Callosity and toe
      deformity were the most common foot and ankle problems found in Thai monks,
      especially those with prolonged period of barefoot walking and long-term duration
      ofordainment. The unique pattern of walking and sitting of Thai monks may have
      contributed to the development of those feet and ankle problems.

PMID- 25775736
TI  - Proximal femoral bone geometry in osteoporotic hip fractures in Thailand.
AB  - BACKGROUND: A number of different bone geometries have been reported to be
      correlated with osteoporosis, bone mineral density and fractures. Those
      correlations are used for diagnosis, treatment and prediction of fracture risk in
      osteoporosis cases. However there have been no studies of significant bone
      parameters predicting osteoporosis and hip fracture in Thailand OBJECTIVE: To
      evaluate the correlation between geometric parameters of the proximal femur and
      both the Singh index and bone mineral density as well as to investigate the
      relationship between those two metrics and osteoporotic hip fracture in the Thai
      population. MATERIAL AND METHOD: Forty-four Thai patients with osteoporotic hip
      fractures andforty-five healthy Thai people matched for age and gender were
      included in the present study. Bone mineral density and bone geometry from plain
      hip radiographs of non-fracture sites in the fracture group and proximal femur
      radiographs of the same site in the healthy group were measured That data were
      analyzed to determine levels of correlation. Bone geometries were also analyzed
      to determine hip fracture predictive capacity. RESULTS: Correlation between the
      Singh index and bone mineral density was significant (p < 0.01), with a moderate
      degree of agreement. The radiograph measurement of the width ofthefemoral medial
      neck cortex was the only parameter which was statistically significantly
      correlated with both osteoporosis and with osteoporotic hip fracture (p = 0.014
      and p = 0.035, respectively). Each 1 mm reduction in the width of the femoral
      medial neck cortex increased the osteoporotic hip fracture risk by a factor of
      2.7 (OR = 0.37, 95% CI = 0.15-0.93). CONCLUSION: In the Thai population, bone
      geometry from plain radiographs can help predict the risk of osteoporotic hip
      fracture. Osteoporosis is correlated with a low Singh index value. The width of
      the femoral medial neck cortex is a reliable predictor of hip fracture risk.

PMID- 25775737
TI  - Pull-out strength of 0 degrees /30 degrees  Kirschner wire syringe external
      fixators with and without polymer augmentation: a biomechanical study.
AB  - BACKGROUND: Hand external fixators are in use worldwide and insulin syringes can
      generally be found in an operating room. OBJECTIVE: To compare the pull-out
      strength between degrees of Kirschner wire fixation (0 degrees  and 30 degrees )
      and the effect of filling an insulin syringe with polymer MATERIAL AND METHOD:
      Pull-out strength was compared between a syringe externalfixator and a bone or
      plastic tube model. Fifty-two plastic tube models and 20 dry phalangeal bones
      were included The syringe external fixator was attached via two Kirschner wires.
      Four variations were studied: 0 degrees  non-polymer 0 degrees  with polymer
      augmentation, 30 degrees  non-polymer and 30 degrees  with polymer augmentation.
      The pull-out strength was measured in each group. RESULTS: The strength of
      polymer augmentation was higher than non-polymer augmentation at 0 degrees  (p =
      0.0003) and 30 degrees  (p = 0.0002). The Kirschner wire at 30 degrees  provided
      more pull-out strength than at 0 degrees  (p = 0.0003) using the syringe with no
      polymer However, using the syringe with polymer augmentation, there was no
      significant difference (p = 0.5136). CONCLUSION: Polymer augmentation
      significantly increases the pull-out strength at both degrees offixation. The
      degree of fixation significantly increases the pull-out strength only in the non
      polymer group, where pinning at 30 degrees  was superior to 0 degrees .

PMID- 25775738
TI  - Results of shortened program of Ponseti technique for congenital clubfoot.
AB  - OBJECTIVE: To study the results and complications of congenital clubfoot
      treatment using a shortened (twice a week) program of serial casting using
      Ponseti technique. MATERIAL AND METHOD: Sixteen patients with congenital clubfoot
      (26 feet) were treated by serial manipulation and casting twice a week until
      acceptable deformity correction (60 degrees of abduction with or without equinus
      deformity) were achieved RESULTS: Seventeen patients (65%) required less than
      three weeks in treatment to improvement in the deformity, while eight patients
      (30%) required more than three weeks of treatment. This period of treatment is at
      least two weeks shorter than the conventional Ponseti technique. One patient did
      not complete treatment due to hospital-acquired pneumonia. Four patients who
      developed pressure ulcers from the castings were continued in treatment and all
      achieved successful correction. CONCLUSION: A shortened program of clubfoot
      correction using the Ponseti technique can be effective for correcting
      uncomplicated clubfoot without serious complications.

PMID- 25775739
TI  - Revision primary total hip replacement: causes and risk factors.
AB  - OBJECTIVE: To determine 1) causes of failure of primary total hip replacement
      (THR) in Thai patients and 2) whether patient characteristics, underlying
      diagnosis, and type of primary THR were associated with the causes of revision
      THR. MATERIAL AND METHOD: The authors retrospectively reviewed all revision THRs
      in one referral hospital in Thailand between 2002 and 2012. All medical records
      and radiographic studies were used to identify the causes of primary THR failure.
      Randomly selected primary THRs performed in the same period were used to compare
      with revision THRs to determine the risk factors for revision. RESULTS: This
      study included 219 THRs. After 5 years (late failure) from index surgery, 138
      primary THRs (63.0%) were revised. Late failures were aseptic loosening (75.4%)
      followed by periprosthetic fracture (8.0%), and polyethylene wear (5.8%). The
      major reasons for revision surgery within 5 years (early failure) were
      periprosthetic joint infection (29.6%), aseptic loosening (28.4%), and
      instability (22.2%). Age < 45 at index surgery had the lowest risk for revision
      with a hazards ratio of 0.695 (95% CI 0.492-0.981). Hybrid fixation was found to
      be a risk factor for revision THR with a hazards ratio of 1.652 (95% CI 1.166
      2.341). CONCLUSION: Most THRs failed after 5 years. Periprosthetic joint
      infection was the most common cause of failure in the early period. Aseptic
      loosening was a major cause of failure in the late period and overall in both
      periods. Hybrid fixation is an independent risk factor for revision surgery after
      primary THR. Younger patients at the time of primary THR were associated with a
      reduced risk for failure.

PMID- 25775740
TI  - Surgical results of old distractive-flexion injury of subaxial cervical spine:
      report of ten cases.
AB  - BACKGROUND: Acute distractive-flexion injury of subaxial cervical spine (C3-C7)
      results in facet subluxation or dislocation. However, when the injury is missed
      or neglected, it may cause serious complications including axial pain, deformity
      and neurological deficit. OBJECTIVE: To demonstrate the pathoanatomy,
      presentation and management of these injuries. MATERIAL AND METHOD: The present
      study was conducted retrospectively at Chiang Mai University Hospital during 2008
      2011. Ten patients were classified as to whether 2 unilateral/2 bilateral
      subluxation or 1 unilateral/5 bilateral dislocation. Pain, neurological status,
      imaging and bony fusion were recorded. RESULTS: The average timing before
      achieving treatment was 52 days. Five patients had arm pain and radiculopathy;
      the other 5 had myelopathy. Nine of 10 patients had posterior element fractures.
      No disc herniation was found. Pain and neurological status were improved after
      surgical decompression, realignment, stabilization and fusion. Bony fusions were
      achieved in all follow-up patients. CONCLUSION: Most patients have posterior
      element fractures without any evidence of intervertebral disc herniation. Spinal
      malalignment is the main cause of neurological impairment. Posterior-anterior
      approach is the favorable approach for old dislocation. Anterior approach is
      preferred for subluxation.

PMID- 25775741
TI  - Wide awake technique versus local anesthesia with tourniquet application for
      minor orthopedic hand surgery: a prospective clinical trial.
AB  - BACKGROUND: Most minor hand operations can be performed with local anesthesia and
      tourniquet. Some literature supports this concept based on the believe that the
      "patient can tolerate it". Nowadays, the wide-awake technique with epinephrine-
      contained lidocaine is safe. This technique does not need a tourniquet because
      epinephrine provides local vasoconstriction. OBJECTIVE: The present study was
      designed to compare patients' comfort and effectiveness of local anesthesia as
      well as bleeding at the surgical site between wide-awake anesthesia and local
      lidocaine with tourniquet application. MATERIAL AND METHOD: Prospective Clinical
      Trial was performed in 60 patients who received outpatient surgery for common
      hand problems at Maharaj Nakorn Chiang Mai Hospital. With randomization, 30
      patients were in wide-awake group, who received adrenaline-contained lidocaine as
      a local anesthetic agent, with tourniquet wrapping but with no pressure applied
      (group 1). The other 30 patients were in the conventional group that received
      lidocaine (no adrenaline) and a 250-mmHg tourniquet application (group 2).
      Operations were performed with standard methods. Visual analog scores, surgical
      field bleeding, amount of bleeding, any complications within 4 weeks were
      recorded. RESULTS: There are no significant differences between the two groups in
      terms of patient profiles (sex, age and diseases), injected site pain and
      surgeon's opinion of surgical site bleeding. Tourniquet's pain and the amount of
      blood loss in the conventional group were significantly higher than the wide
      awake group. CONCLUSION: Wide-awake technique (no tourniquet applied) offers
      better comfort for patients and less total blood loss while providing effective
      anesthesia and patient safety as with the conventional technique.

PMID- 25775742
TI  - Negative pressure wound therapy for traumatic foot and ankle wound: two case
      reports and review of the literature.
AB  - This report describes treatment of patients who presented with open soft tissue
      injuries andAchilles tendon tears at the posterior ankle and heel from accidents.
      After appropriate debridement and/or Achilles tendon repair a large wound defect
      remained as well as a bare Achilles tendon. Negative pressure wound therapy was
      applied to the Achilles tendon to promote wound healing and healthy granulation.
      The size of wound decreased and the Achilles tendon was completely covered with
      granulation within two weeks. The remaining granulation tissue without tendon
      exposure was completely healed with secondary wound healing and/or skin grafting
      during the following two weeks after which motion of the ankle was satisfactory.
      Negative pressure wound therapy is an optional treatment for the complicated
      wounds where reconstructive surgery with a skin flap cannot be performed.

PMID- 25775743
TI  - [The new progress of diagnosis and treatment of peripheral vertigo disease].

PMID- 25775744
TI  - [Four bacterial studies on children with chronic otitis media with effusion].
AB  - OBJECTIVE: To research the prevalences of four kinds of bacteria including
      Alloiococcus otitidis, Streptococcus pneumonia, Haemophilus influenzae, and
      Moraxella catarrhalis in children with chronic otitis media with effusion (SOM)
      of the middle ear effusion, and the reproduction of the nasopharynx, so as to
      explore their meaning for the children with SOM. METHOD: Alloiococcus otitidis,
      Streptococcus pneumonia, Haemophilus influenza, and Moraxella catarrhal were
      investigated in the samples obtained from middle ear effusion and nasopharyn-
      geal swabs, using PCR and conventional bacterial culture methods. RESULT: By
      bacterial culture, the pathogen detection rate from middle ear effusion was
      3.6%,while the nasopharynx was 54.0%, the detection rate of Streptococcus
      pneumonia, Haemophilus influenza, Moraxella catarrhalis was 10.8%, 27.0%, 4.5%,
      respectively, the drug susceptibility results for 51 samples of bacterial culture
      positive showed that 39 cases was sensitivite to the beta-lactam antibiotic; By
      PCR, the number of detecting various kinds of bacteria simultaneously in middle
      ear effusion or in the nasopharynx were 6 and 34. The bacteria prevalences of S.
      pneumoniae, H. influenzae, M. catarrhalis, and A. otitidis are 5.4%, 5.4%, 3.6%,
      and 42.3% in the middle ear effusion, are 25.2%, 27.0%,13.5% and 34.2% in
      nasopharyngeal, respectively. CONCLUSION: (1) PCR method is more sensitively
      detecting the bacteria than conventional bacterial culture methods. (2) The
      chronic SOM of children may be a combination of mixed bacterial infection, A.
      otitidis may be the most common pathogen of children SOM. (3) For children of
      SOM, if antibiotics are chosen to be used early in the disease, we suggest using
      the beta-lactam antibiotics.

PMID- 25775745
TI  - [Tone recognition ability for post-lingually deafened cochlear implant users
      using pitch information].
AB  - OBJECTIVE: The present study was aimed to assess the ability of tone recognition
      performance for postlingually deafed cochlear implanted adults using no-duration
      tone test materials. METHOD: Sixteen cochlear implanted users have used their
      devices at least six months. Ten monosyllabic syllables were selected, and
      combined with four lexical tones which were made up of 40 tone tokens. Then,
      these original words were recorded using one adult male and one adult female
      native Beijing Mandarin speaker. The speakers were asked to record these 40
      monosyllabic words multiple times, and the 80 tokens in which the durations of
      four tones in each monosyllabic word were within 5 ms precision were chosen as
      the original tone tokens. The subjects were asked to perform a four alternative
      forced-choice study and select the tone they had heard. RESULT: The mean score of
      lexical tone perception tasks for 16 cochlear implanted users is (70.7 +/-
      22.0)%, and Tone 4 was the easiest to perceive, while Tone 2 was the hardest for
      cochlear implanted subjects to perceive. Tone 1 was more often misperceived as
      Tone 2 relative to other tones. Tone 2 was more often misperceived as Tone 1 and
      3. Tone 3 was more often misperceived as Tone 2. The tone perception performance
      was positively correlated with duration of hearing aid use. CONCLUSION: Duration
      cues may impact on the ability of tone recognition performance for cochlear
      implant subjects, especially for tone 3. Due to the limited ability for cochlear
      implant subjects on pitch perception, tone l and tone 2, and tone 2 and tone 3
      are most often confused with each other without duration cues. The experience of
      hearing aid use may benefit for postlingual deafness cochlear implant recipients
      on tone perception performance.

PMID- 25775746
TI  - [Clinical application of heterogeneous acellular dermal matrix with autologous
      bone meal in open tympanoplasty].
AB  - OBJECTIVE: To evaluate the clinical value of heterogeneous acellular dermalmatrix
      with autologous bone meal in open tympanoplasty. METHOD: Twenty-eight cases (30
      ears) with middle ear cholesteatoma were trea- ted by open tympanoplasty and
      repaired by heterogeneous acellular dermalmatrix autologous bone meal on study
      team. Twenty-two cases (22 ears) with middle ear cholesteatoma were treated by
      open tympanoplasty on control team. All patients were followed up for 12 to 18
      months and assessed the fuction postoperatively. RESULT: The re- construction of
      external auditory canal structure is close to normal, and no narrow happens on
      study team. The rate of dry ear was about 90%. All cases had no recurrence of
      cholesteatoma. CONCLUSION: Application of decellu- larized dermal matrix with
      autologous bone meal can rise early to cover the wound, promote wound healing and
      to reduce the external auditory canal, reduce the effect of granulation and scar
      formation. It is a kind of method of repair to be promoted.

PMID- 25775747
TI  - [The treatment of benign positional paroxysmal vertigo of posterior semicircular
      canal by Epley maneuver combined with Semont maneuver].
AB  - OBJECTIVE: To investigate the treatment of benign positional paroxysmal vertigo
      of posterior semi-circular canal by Epley maneuver combined with Semont maneuver.
      METHOD: One hundred and fifty patients with benign positional paroxysmal vertigo
      of posterior semicircular canal were randomly divided into three groups: group A,
      B and C. Patients in group A were treated by Epley maneuver and patients in group
      B were treated by Semont maneuver. Patients in group C were received the
      treatment of Epley maneuver combined with Semont ma- neuver. We recorded the
      times of treatments in different groups respectively. Statistics of treatment
      effects and follow-up studies with 3 months after the recovery were assessed.
      RESULT: The cure rate of the canalith repositioning on the primary, secondary and
      tertiary treatment in group A was respective 72% (38/53) and 81% (43/53) and 85%
      (45/53), in group B was 68% (30/44) and 80% (35/44) and 84% (37/44), in group C
      was 89% (47/53) and 94% (50/53) and 98% (52/53). The cure rate in group C is
      significantly higher than group A and group B (chi2 = 6.777, P < 0.05; chi2 =
      6.647, P < 0.05). 3 months after recovery 6 patients in group A, 5 patients in
      group B and 1 patient in group C were relapsed. CONCLUSION: By the use of Epley
      maneuver combined with Semont maneuver in the treatment of benign positional
      paroxysmal vertigo of posterior semicircular canal, the primary cure rate was
      increased and the numbers of treatments were reduced and the relapse was
      decreased. It is suitable to use Epley maneuver combined with Semont maneuver in
      the clinic.

PMID- 25775748
TI  - [Clinical study on vocal cords spontaneous rehabilitation after CO2 laser
      surgery].
AB  - OBJECTIVE: To study the spontaneous rehabilitation and phonation quality of vocal
      cords after different types of CO2 laser microsurgery. METHOD: Surgical
      procedures based on Remacle system Type I, Type II, Type III, Type IV and Type V
      a respectively. Three hundred and fifteen cases with hoarseness based on strobe
      laryngoscopy results were prospectively assigned to different group according to
      vocal lesions apperence,vocal vibration and imaging of larynx CT/MRI. Each group
      holded 63 cases. The investigation included the vocal cords morphological
      features,the patients' subjective feelings and objective results of vocal cords.
      RESULT: There are no severe complications for all patients in perioperative
      period. Vocal scar found in Type I ,1 case; Type II, 9 cases ;Type III, 47 cases;
      Type IV, 61 cases and Type Va 63 cases respectively after surgery. The difference
      of Vocal scar formation after surgery between surgical procedures are statistical
      significance (chi2 = 222.24, P < 0.05). Hoarseness improved after the surgery in
      59 cases of Type I , 51 cases of Type II, 43 cases of Type III, 21 cases of Type
      IV and 17 cases of Type Va. There are statistically significance (chi2 = 89.46, P
      < 0.05) between different surgical procedures. The parameters of strobe
      laryngoscope: there are statistical significance on jitter between procedures (F
      44.51, P < 0.05), but without difference within Type I and Type II (P > 0.05).
      This happened in shimmer parameter and the maximum phonation time (MPT) as
      jitter. There are no statistical significance between Type IV and Type Va on MPT
      (P > 0.05). CONCLUSION: Morphological and functional rehabilitation of vocal cord
      will be affected obviously when the body layer is injured. The depth and range of
      the CO2 laser microsurgery are the key factors affecting the vocal
      rehabilitation.

PMID- 25775749
TI  - [Clinical analysis of the treatment for benign tumor of external auditory canal
      by carbon dioxide laser under microscope].
AB  - OBJECTIVE: To investigate the treatment for benign tumor of external auditory
      canal by carbon dioxide laser under microscope. METHOD: Ten cases of benign tumor
      of external auditory canal were treated by carbon dioxide laser under microscope.
      The curative effects and complications were observed. RESULT: Ten cases of benign
      tumor of external auditory canal were satisfied after operation without any
      complications. There were no recurrences during 3 months to 2 years of follow up.
      CONCLUSION: The operation for benign tumor of external auditory canal by carbon
      dioxide laser under microscope was easy, safe and effective.

PMID- 25775750
TI  - [Central lymph node metastasis in cNO papillary thyroid carcinoma].
AB  - OBJECTIVE: This study was to evaluate the patterns of central lymph nodes
      metastasis, by analyzing the results of surgery in clinical NO (cNO) papillary
      thyroid carcinoma (PTC). METHOD: We retrospectively studied the effect of
      surgical treatment among 123 cN0 PTC patients. All the patients underwent central
      lymph node dissection; 47 patients underwent ipsilateral neck dissection and 9
      patients underwent bilateral neck dissection. RE- SULT: Seventy-eight cases
      (63.4%)were found positive central lymph node, which included 34 cases (27.6%)
      bilateral positive central lymph node. Central lymph node metastases correlated
      with age < 45 years, extrathyroidal extension, surrounding tissue invasion and
      tumor size grade (P < 0.05), were the independent risk factors of central lymph
      node metastasis. CONCLUSION: Age < 45 years, extrathyroidal extension and
      surrounding tissue invasion were the independent risk factors of central lymph
      node metastasis. For cNo patients with PTC, primary excision as well as central
      neck dissection was recommended; according to the results of intraoperative
      frozen and situation, further process were made.

PMID- 25775751
TI  - [Effects of intratympanic injection of dexamethasone on endolymphatic hydrops and
      changes in guinea pigs inner ear CFTR expression].
AB  - OBJECTIVE: To observe the effect of tympanic injection of dexamethasone in the
      guinea pig endolymphatic hydrops and the change CFTR expression, to explore the
      effect of glucocorticoid treatment endolymphatic and its possible mechanism.
      METHOD: Thirty guinea pigs were divided into three groups: hormone group, water
      group, control group. The animals(hormone group, water group) in study were
      injected DDAVP 4 MUg/kg in the first 7 d, and will increase to 6 MUg/kg in the
      second 3 d. The control group was given normal saline, continuous 10 d. After
      twelfth days, the hormone group transtympanic injection of dexamethasone (5
      mg/ml, 0.5 ml), and water group, control group transtympanic given normal saline
      (0.5 ml), continuous injection 5 d. Using immuno- histochemistry and Western blot
      to detect the cystic fibrosis transmembrane conductance regulator cochlear factor
      (CFTR) expression. RESULT: The water group ABR thresholds was significantly
      higher than that before the experiment (P < 0.01), and the water group was
      significantly higher than the rest of the groups (P < 0.01); Hormone group
      compared with the control group increased threshold value (P < 0.05). The control
      group had no endolym- phatic hydrops, the water group showed varying degrees of
      endolymphatic hydrops, cochlear duct and vestibular plus cochlear duct area ratio
      compared with the control group, hormone group was significantly higher (P <
      0.01). hormone group area ratio was higher than the control group (P < 0.05).
      CFTR was primarily expressed in the stria vascularis, Corti's, spiral ligament,
      basilar membrane, cochlear ganglion,etc . The expression of CFTR in the water
      group was increased than that in the control group, and the hormone group (P <
      0.01); the expression of hormone group increased compared with the control group
      (P < 0.05). CONCLUSION: Tympanic injection of dexa- methasone can alleviate the
      desmopressin acetatein guinea pigs caused by membranous labyrinth, and the
      improve- ment of the hearing; Tympanic injection of dexamethasone can make the
      endolymphatic hydrops cochlea of guinea pigs decreased CFTR expression,
      indicating that the expression and possible mechanisms of CFTR intratympanic
      steroids reduce endolymphatic hydrops changes.

PMID- 25775752
TI  - [The application of CAD/CAM technology on the reconstruction of the thyroid
      cartilage].
AB  - OBJECTIVE: To explore the value of computer-aided design/computeraided
      manufacturing (CAD/CAM) technology for individual reconstruction of the thyroid
      cartilage defects. METHOD: Select the 20 New Zealand white rabbits (male or
      female). Randomly divided into two groups. Group A in the pre-operative CT scan
      of the throat, three-dimensional reconstruction of the thyroid cartilage imaging,
      surgical removal of either side of the thyroid cartilage, defect implanted in the
      use of CAD/CAM technology and mirror technology to produce personalized
      restorative materials; Group B surgical resection either side of the thyroid
      cartilage, defect implanted production of non-personalized probably according to
      the experimental animals unilateral thyroid cartilage repair materials. After
      surgery by gross observation, electronic laryngoscopy observed experimental
      animals throat. RESULT: General check and electronic laryngoscopy show: the use
      of CAD/CAM technology to prepare the individual repair materials throat plays
      better supporting role than the non personalized materials. CONCLUSION: CAD/CAM
      technology before surgery designed to provide a personalized solid model to
      improve the accuracy of the surgery, time saving surgery to reduce surgical
      complications.

PMID- 25775753
TI  - [The relationship between the ear protective measures and the prevalence of
      external auditory canal exostoses].
AB  - OBJECTIVE: To determine the relationship between the ear protective measures
      during winter swimming and the prevalence, severity of the incidence of external
      auditory canal exostoses. METHOD: Three hundred and fifteen people who enjoyed
      swimming were recruited as research subject (62.2% males and 37.8% females; age
      distribution: 4.4% were <= 40, 40.3% were 41 to 60, and 55.2% were > 60 years).
      People fill in the questionnaires including personal information, the ear
      protection measures, the time of winter swimming, the history of ear infections
      and so on, and questionnaires were correlated with otoscopic findings. We
      classify external auditory canal exostoses according to the degree of the
      stenosis of external auditory canal s. Grades of normal,mild, moderate and severe
      corresponded to 100%, 99% to 66%, 65% to 33%, and less than 33% respectively.
      RESULT: Of 110 ears with exostoses, 63.6% were mild, 23.6% were moderate, and
      12.7% were severe. Among the group of without ear protection during winter
      swimming, about 33.0% have auditory canal exostoses and 4.6% were severely
      affected. In comparison, in the group that had ear protection, only 2.8% had
      external auditory canal exostoses and no one had severely obstructed auditory
      canal. CONCLUSION: A negative association exists between the ear protection
      measures during winter swimming and the prevalence and severity of exostoses of
      the external auditory canal. That means taking ear protective measures when
      having winter swimming can prevent the onset of the external auditory canal
      exostoses and reduce its severity.

PMID- 25775754
TI  - [The additional 180 degrees  roll test in the determination of affected side of
      horizontal semicircular canal benign paroxysmal positional vertigo].
AB  - OBJECTIVE: To evaluate the significance of additional 180-degree roll test (RT)
      in the determination of affected side in patients with horizontal semicircular
      canal benign paroxysmal vertigo (HSC-BPPV). METHOD: One hundred and six patients
      with HSC-BPPV were performed the 90 degree RT. patients whose affected side
      cannot be determined by 90 degree RT were performed 180 degree roll test. RESULT:
      The affected side was deter- mined by the 180 degree RT in 10 cases in which the
      lesion side cannot be determined by the 90-degree RT. CONCLUSION: The affected
      side of HSC BPPV was able to be determined by 180 degree RT when it not possible
      to be determined by 90 degree RT. 180 degree RT is an effective and simple
      additional method.

PMID- 25775755
TI  - [Normal value of air-conducted ocular evoked myogenic potential in young people].
AB  - OBJECTIVE: To investigate the characteristics of air-conducted ocular vestibular
      evoked myogenic potential (oVEMP) in healthy young people , so as to establish
      the normative data of young people. METHOD: Fifty-five healthy young subjects
      were recruited as study participants, 500 Hz air-conducted tone burst was used as
      stimulation. The threshold of oVEMP in each ear was examined. The latencies of P1
      and N1, P1-N1 interval, peak-to-peak of P1-N1 amplitude and asymmetry ratio were
      measured. Effects of gender on oVEMPs were also exam- ined. RESULT: The typical
      complex wave of N1 and P1 was observed in all subjects. The threshold of oVEMP
      examination was(82.23 +/- 12.92) dBHL, 95 dBHL air-conducted get the latencies of
      P1 and N1, P1-N1 interval,peak-to-peak P1-N1 amplitude in these healthy young
      people were(11.53 +/- 0.80)ms, (16.61 +/- 0.87)ms, (5.18 +/- 11.04)ms, (5.96 +/-
      2.59)MUv, respectively. The peak-to-peak P1-N1 amplitude of male was (6.49 +/-
      2.67) MUv ,the female was (5.21 +/- 2.34) MUv, there were significant differences
      between male and female subjects in the wave amplitude (P < 0.05). CONCLUSION:
      Air-conduction induced oVEMP is a new method for vestibular function test. The
      amplitude of the oVEMP wave was different between male and female. Therefore it
      is necessary to establish the normal value according to genders.

PMID- 25775756
TI  - [The influence of drinking on high frequency hearing loss of pilot students].
AB  - OBJECTIVE: To evaluate the influence of drinking on hearing loss of pilot
      students, especially on high frequency hearing loss. METHOD: According to whether
      drinking, 517 male pilot students were divided into two groups. The balance of
      all the factors in addition to drinking in both groups was compared. All the
      students were examined by pure tone audiometry. The statistical data of this
      research was processed based on a retrospective cohort study. RESULT: The damage
      of high frequency (4-8 kHz) auditory threshold in left and right ear in drinking
      group were obviously higher compared with control group (P < 0.01). The Morbidity
      of hearing loss in drinking group was significantly higher compared to control
      group (chi2 =16.620, P < 0.01). CONCLUSION: Drinking is associated with the
      hearing loss in pilot students and particularly affects the hearing of high
      frequency spectrum.

PMID- 25775757
TI  - [Effects of endoscopic surgery on patients with chronic rhinosinusitis with
      bronchial asthma].
AB  - OBJECTIVE: To investigate the efficacy of endoscopic sinus surgery (ESS)-based
      multidisciplinary therapy for patients with chronic rhinosinusitis (CRS), nasal
      polyps and bronchial asthma. METHOD: The study included 32 patients with CRS,
      nasal polyps and bronchial asthma who received ESS, besides surgery, who also
      used glucocorticoid inhalation, nasal spray and nasal irrigation perioperatively.
      The evaluation of the treatment was performed 3 years post after ESS. RESULT: In
      the 32 cases treated with ESS, 19 cases were cured, 9 cases were improved, 4
      cases were inefficient by the treatment. The cure rate was 87.5%. The asthma
      symptoms were improved in 9 patients (P < 0.01), compared to 2 before surgery.
      The numbers of patients with improved symptoms were increased from 2 before the
      surgery to 9 after the surgery. CONCLUSION: As the main treatment, endoscopic si-
      nus surgery was effective on CRS with asthma.

PMID- 25775758
TI  - [Twenty-six clinical case analysis of defect repairing after the resection of
      basal cell carcinoma on external nose].
AB  - OBJECTIVE: To study a surgical and repairing method for defects after the
      resection of basal cell carcinoma of external nose. METHOD: There are 26 cases of
      basal cell carcinoma that tumors have been resected completely after operation.
      For defect repairing in those 26 cases, 2 cases adopt direct suture method; 2
      cases use skin graft repairing methods; 18 cases employ naselabial skin flap
      repairing method; 4 cases choose forehead pedicle skin flap repairing methods.
      RESULT: the wound of all the 26 cases was primary healed. Additionally, skin flap
      and skin graft were all survived. Follow-up studied in patients 1 to 3 years
      after the surgery showed that the local scar was not obvious and no tumor
      recurred or transferred. CONCLUSION: Different surgical and repairing methods are
      performed to obtain a satisfactory results based on the area of defect and its
      location in nose. Naselabial skin flap is especially an ideal method to repair
      defects.

PMID- 25775759
TI  - [Clinopahological analysis of sinonasal mucosal malignant melanoma].
AB  - OBJECTIVE: To investigate the clinopathological characteristics, differential
      diagnosis, therapy and prognosis of sinonasal mucosal malignant melanoma. METHOD:
      Clinopathological data of 18 cases which were diagnosed by pathology and
      immmunohistochemistry were analyzed retrospectively. All cases were proved by
      pathology and immmunohistochemistry. All cases were performed operations. 5
      underwent single surgery. 4 underwent surgery plus adjuvant radiotherapy. 4
      underwent surgery plus adjuvant radiotherapy chemotherapy. 5 underwent surgery
      plus adjuvant chemoradiation. RESULT: All cases were followed up for a period of
      1 to 7 years after operation. Twelve patients died of tumor until the last follow
      up, meanwhile 6 patients stayed alive. In Six cases recurrence occurred. In five
      casescervical lymph node metastasis occurred, of which 3 cases received neck
      dissection and 2 cases received chemotherapy and radiotherapy due to no surgical
      indications. In three cases distant metastasis oc- curred. CONCLUSION: Sinonasal
      mucosal malignant melanoma is rare and highly heterogenous. Current diagnosis
      depends on clinical characteristics and immunohistochemical examination. It still
      should be differentially diagnosed from other tumors. CT and MRI image
      examination can provide some helpful information to understand the extent and
      nature of lesions. The treatment of nasal endoscopic or the surgery under
      endoscopy has become to be a safe, viable and reasonable alternative to open
      resection. Appropriate indication must be carefully selected for these lesions.

PMID- 25775760
TI  - [The effect and the analysis of the influence factors of sublingual immunotherapy
      on patients with pharyngitis and allergy to house dust mite].
AB  - OBJECTIVE: To evaluate the effect of sublingual specific immunotherapy (SLIT) on
      patients with pharyngitis and allergy to house dust mite and to discuss the
      influence of different treatments, single and multiple allergen sensitization and
      genders on SLIT. METHOD: We recorded the total medicine score (TMS) and self
      evaluation of 53 patients with pharyngitis and allergy to house dust mite before
      and 6 months after the treatment. Control group included 25 patients only treated
      with anti-allergic drugs. Treatment group included 28 patients accept SLIT. Based
      on different dosage regimens, treated patients were divided into SLIT group and
      comprehensive group; Based on the results of skin prick, treated patients were
      divided into dust mite group and multiple group; Based genders, treated patients
      were divided into male and female group. We compared the effective rate (ER)and
      decreasing percent of TMS (Dp-TMS) between control and treatment group, and also
      different groups in treatment group. RESULT: The ER and Dp-TMS of treatment group
      is significantly higher than control group, (P < 0.01). The ER of SLIT and
      comprehensive group respectively is 72.73% and 76.47%without significant
      difference (P > 0.05). The ER and Dp-TMS of dust mite group and multiple group
      respectively is 61. 54%, 94. 46%,66. 67%, 71.25% without significant difference
      (P > 0.05). The ER and Dp-TMS of male and female respectively are 58.33%, 66.67%,
      83.33%, 97.04% with significant difference (P > 0.05), while the Dp-TMS is not (P
      > 0.05). CONCLUSION: The SLIT is effective to patients with pharyngitis and
      allergy to house dust mite; The therapeutic schedule, single and multiple
      allergen sensitization have no effects on SLIT in patients with pharyngitis and
      allergy to house dust mite. However, genders have influence on it.

PMID- 25775761
TI  - [Clinical observation of coblation under endoscopy on epiglottis cyst].
AB  - OBJECTIVE: To evaluate the effect of the coblation under endoscopy on epiglottis
      cyst. METHOD: One hundred and ninety-three patients with epiglottis cyst were
      treated with coblation under endoscopy. Follow-up study was performed from 1
      month to 6 months after treatments. RESULT: All 193 cases with epiglottis cyst
      were primary cured without serious complication and the cure rate was 100%.
      Moreover, the minor hemorrhage (1-5 ml) was observed. CONCLUSION: The coblation
      under endoscopy on epiglottis cyst was safe, effective and minimally invasive.

PMID- 25775762
TI  - [Clinical analysis of lung cancer with initial symptoms in the head and neck].

PMID- 25775763
TI  - [The clinical application value of Multi-Slice Spiral CT and image post
      processing technology in the diagnosis of air tract foreign body in children].

PMID- 25775764
TI  - [Clinical analysis of the therapeutic effect of patients with gestational
      hypertension combined with obstructive sleep apnea hypopnea syndrom].

PMID- 25775765
TI  - [Riedel thyroiditis: two cases report].
AB  - Riedel thyroiditis is a benign disease, which is often self-limited.
      Examinations, such as CT and histologic diagnosis can distinguish it from
      malignant neoplasms and hashimoto's thyroiditis. Riedel thyroiditis is an
      uncommon form of chronic thyroiditis in which the thyroid gland is replaced by
      fibrous tissue. It can be cured by surgery and medicine.

PMID- 25775766
TI  - [One case of head and facial angiosarcoma].
AB  - Summary The clinical manifestaion includes purple or red patches and nodules,
      dark red appearing on head and face. Physical examination showed facial swelling
      with lymph nodes. CT examination demonstrated both diffuse swelling of facial
      soft tissue and multiple cervical lymph nodes. Platelet significantly reduced.
      Pathological examination: angiosarcoma.

PMID- 25775767
TI  - [Clinical analysis of acute invasive fungal sinusitis with orbital infection].
AB  - The clinical manifestation of acute invasive fungal sinusitis was associated with
      facial pain,altered sense of smell, blindness and headache. Physical examinations
      show that dark brown nasal secretions with bone resorption in paranasal sinus.
      Radiographi parameters showed uneven density in paranasal sinus and intraorbital
      extension. Fungus smears and pathological examination can make a definitive
      diagnosis.

PMID- 25775768
TI  - [A case of secondary bleeding after tonsentectomy].
AB  - One case of secondary bleeding repeatedly after tonsillectomy. Secondary bleeding
      after tonsillectomy seldom happen to us. When the event occurs medical staff has
      to take effect way to control the bleeding immediately. Accumulated quantity of
      bleeding must be controlled to the lowest point as soon as possible. Other wise
      the bleeding may lead to death. This point should be considered by medical staff.

PMID- 25775769
TI  - [Two cases of epiglottic neuroendocrine carcinoma].
AB  - Neuroendocrine tumors of the epiglottis were extremely rare. Patients normally
      had no obvious symptoms and signs of early stage. Epiglottis lingual except
      (without) tubercle of epiglottis, and hyperplastic mass were observed by using
      laryngoscopy and also confirmed by biopsy and immunohistochemistry. Immunohis-
      tochemical studies showed that Syn, a broad spectrum endocrine marker, and CgA, a
      specific marker of endocrine tumor, were both positive. Which is consistent with
      the diagnosis of neuroendocrine carcinoma.

PMID- 25775770
TI  - [The effects on psychological health of patients with hearing loss].
AB  - Previous studies have shown that hearing loss people are more likely to have not
      only abnormal speech communication, but also psychological problems especially
      emotional disorders, cognitive impairments and personality defects. Therefore, it
      is necessary to provide psychological support to patients during they accept
      medical therapy.

PMID- 25775771
TI  - [Discussing the objective diagnostic methods of laryngopharyngeal reflux].
AB  - Laryngopharyngeal reflux (LPR) is gaining extensive attention in recent years
      because of the high incidence. But because of the complex symptoms and signs,
      there exist no diagnostic consensus. In this paper, the available objective
      diagnostic methods so far are reviewed, in the purpose of discussing the approach
      of objective and accurate diagnosis of LPR.

PMID- 25775772
TI  - [Recognition of experimental animal model with kidney disease].
AB  - Animal models with kidney disease are generally divided into two types. One
      belongs to the models which imitate human kidney disease by the artificial
      operations, such as anti-glomerular basement membrane antibody nephritis, Heymann
      nephritis, anti-Thyl. 1 antibody nephritis, BSA nephritis and puromycin
      nephropathy. The other one pertains to the models which make themselves kidney
      disease, and appear the pathological characteristics naturally as like as human,
      such as HIGA mice with IgA nephropathy and NZB/WF1 and MRL/1pr mice with lupus
      nephritis. In addition,the transgenic animal models with kidney disease can also
      be established by the modern molecular biologic techniques including gene
      knockout and siRNA transfection. As for the studies related with kidney disease
      in pharmacodynamics and pharmacology of Chinese herbal medicine (CHM), it is
      important to understand deeply the features of each animal model with kidney
      disease, and select accurately the proper models according to the different
      experimental objectives, and then, build the special models provided with the
      combination of disease with syndrome in traditional Chinese medicine (TCM).
      Therefore,it is the developmental direction for the further study to establish
      animal models with kidney disease, which should possess the characteristics of
      syndrome in TCM.

PMID- 25775773
TI  - [Effects and mechanisms of Qifu decoction ameliorating renal tubulointerstitial
      fibrosis through inhibiting ERK1/2 signaling pathway in unilateral ureteral
      obstruction rats with yang deficiency].
AB  - OBJECTIVE: To demonstrate the effects and mechanisms of Qifu decoction( QFD) on
      renal interstitial fibrosis (RIF) in model rats with yang-deficiency syndrome.
      METHOD: The rats were randomly divided into 3 groups, the Sham group (Group A),
      the Model group (Group B), the Qifu decoction group (Group C) and the Enalapril
      group (Group D). The RIF model was established by adenine administrated and
      unilateral ureteral obstruction (UUO) of the left ureter. After the model was
      successfully established, the rats in Group C and D were administrated with QFD
      or the Enalapril suspension,while the rats in Group A and B were administrated
      with distilled water. All rats were administrated for 3 weeks. Before
      administration and at the end of week 1, 2 and 3, the rats were weighted, and 24
      h urinary protein excretion (Upro), urinary beta2-microglobulin (Ubeta2-MG) and
      urinary N-acetyl-D-glucosaminidase (NAG) were examined, respectively. All rats
      were killed after administration for 3 weeks. Blood and renal tissues were
      collected, renal morphology and tubulointerstitial morphology were evaluated,
      respectively. Serum cyclic adenosine monophosphate (cAMP), cyclic guanosine
      monophosphate (cGMP), blood urea nitrogen (BUN), serum creatinine (Scr) and uric
      acid (UA) were detected, respectively. The protein expressions of E-cadherin,
      alpha-smooth muscle actin(alpha-SMA), transforming growth factor-beta1 (TGF
      beta1), onnective tissue growth factor (CTGF) extracellular signal-regulated
      protein kinase 1/2(ERK1/2) and phosphorylated-ERK1/2 (p-ERK1/2) in kidney were
      evaluated, respectively. RESULT: QFD ameliorated serum cAMP level and the rate of
      cAMP/cGMP, attenuated urinary beta2-MG level, NAG level and renal
      tubulointerstitial fibrosis, increased E-cadherin protein expression, and reduced
      alpha-SMA, TGF-beta1, CTGF and p-ERK1/2 protein expressions in the kidney.
      However, QFD had no influence on renal function in vivo. In addition, these
      effects were better than those of the model rats treated by Enalapril.
      CONCLUSION: QFD could alleviate yang-deficiency parameters, as well as urinary
      beta2-MG level and NAG level in model rats induced by adenine administration and
      UUO. Moreover, QFD could improve EMT and RIF by up-regulating E-cadherin protein
      expression, and down-regulating alpha-SMA, TGF-beta1, CTGF and p-ERK1/2 protein
      expressions, the key molecular in ERK1/2 signaling pathway.

PMID- 25775774
TI  - [Molecular mechanism of rhein on inhibiting autophagic protein expression in
      renal tubular epithelial cells via regulating mTOR signaling pathway activation].
AB  - OBJECTIVE: To explore the effects and molecular mechanisms of rhein on reducing
      starvation-induced autophagic protein expression in renal tubular epithelial (
      NRK-52E) cells. METHOD: Hank's balanced salt solution (HBSS) was used to induce
      NRK-52E cells to be in the state of starvation. After the intervention of HBSS
      for 0, 0.5,1, 2 and 6 hours, firstly, the protein expression of microtubule
      associated protein 1 light chain 3(LC3 I/II), which is a key protein in
      autophagy, was detected. Secondly, the protein expressions of mammalian target of
      rapamycin (mTOR) and phosphorylated-mTOR Ser2448 (p-mTOR S2448) were examined.
      And then, after the co-treatment of rhein (5 mg x L(-1)) and HBSS (1 mL) without
      or with mTOR inhibitor, rapamycin (100 nmol x L(-1)), the protein expressions of
      LC3 I/II, mTOR and p-mTOR S2448 were tested, respectively. RESULT: HBSS could
      induce the up-regulation of LC3 II and the down-regulation of p-mTOR S2448 at
      protein expression level in NRK-52E cells. The co-treatment of rhein and HBSS
      could reversely regulate the protein expressions of LC3 II and p-mTOR S2448 in
      NRK-52E cells significantly. The co-treatment of rapamycin, rhein and HBSS could
      recover the level of LC3 II protein expression in HBSS-intervened NRK-52E cells.
      CONCLUSION: HBSS induces autophagy in renal tubular epithelial cells by
      inhibiting mTOR signaling pathway activation. Rhein reduces the autophagic
      protein expression in renal tubular epithelial cells through regulating mTOR
      signaling pathway activation, which is the possible effects and molecular
      mechanisms.

PMID- 25775775
TI  - [Mechanisms of cordycepin on improving renal interstitial fibrosis via regulating
      eIF2alpha/TGF-beta/Smad signaling pathway].
AB  - OBJECTIVE: To investigate the effects and mechanisms of cordycepin,an effective
      component of cordyceps militaris, on renal interstitial fibrosis (RIF) and its
      related eIF2alpha/TGF-beta/Smad signaling pathway. METHOD: Firstly, 15 C57BL/6
      mice were randomly divided into 3 groups,the control group (Group A), the model
      group (Group B) and the cordycepin-treated group (Group C). After renal
      interstitial fibrotic model was successfully established by unilateral ureteral
      obstruction (UUO), the mice in Group C were intraperitoneally administrated with
      cordycepin(5 mg x kg(-1) d(-1)) and the ones in Group A and B were administrated
      with physiological saline for 5 days. At the end of the study, the obstructed
      kidneys were collected and detected for the pathological changes of RIF, and the
      mRNA expressions of collagen type I (Col I) and alpha-smooth muscle actin (alpha
      SMA) in the kidney by Northern blot. Secondly, after renal tubular epithelial
      (NRK-52E) cells cultured in vitro were exposed to transforming growth factor
      (TGF) -beta with or without cordycepin, the mRNA expressions of Col I and
      collagen type IV( Col IV) by Northern blot, and the protein expressions of
      eukaryotic initiation factor 2alpha (eIF2alpha), phosphorylated eIF2alpha ( p
      eIF2alpha), Smad2/3 and phosphorylated Smad2/3 (p-Smad2/3) were tested by Western
      blot. RESULT: In vivo, cordycepin alleviated RIF in model mice, including
      improving fibrotic pathological characteristics and mRNA expressions of Col I and
      alpha-SMA. In vitro, cordycepin induced the high expression of p-elF2alpha, and
      inhibited the expressions of p-Smad2/3, Col I and Col IV induced by TGF-beta in
      NRK-52E cells. CONCLUSION: Cordycepin attenuates RIF in vivo and in vitro,
      probably by inducing the phosphorylation of eIF2alpha, suppressing the expression
      of p-Smad2/3, a key signaling molecule in TGF-beta/Smad signaling pathway, and
      reducing the expressions of collagens and alpha-SMA in the kidney.

PMID- 25775776
TI  - [Effects and mechanisms of multi-glycoside of Tripterygium wilfordii improving
      glomerular inflammatory injury by regulating p38MAPK signaling activation in
      diabetic nephropathy rats].
AB  - OBJECTIVE: To explore the effects and mechanisms of multi-glycoside of
      Tripterygium wilfordii (GTW) on improving glomerular inflammatory lesion in rats
      with diabetic nephropathy (DN). METHOD: DN model was induced by unilateral
      nephrectomy and intraperitoneal injection of STZ (35 mg x kg(-1)) twice. The rats
      were randomly divided into 3 groups, the sham-operated group (Sham group, n = 5),
      the vehicle-given group (Vehicle group, n = 5 ) and GTW-treated group (GTW group,
      n = 5). After the model was successfully established, the rats in GTW group were
      daily oral administrated with GTW suspension (50 mg x kg(-1) x d(-1)), meanwhile,
      the rats in Vehicle group were daily oral administrated with distilled water (2
      mL) for 8 weeks. From the beginning of the administration, all rats were killed 8
      weeks later. Blood and renal tissues were collected,and then UAlb, renal
      function, glomerular morphology characteristics and glomerular macrophages (ED1 +
      cells) infiltration, as well as the protein expressions of inflammatory cytokines
      including tumor necrosis factor(TNF)-alpha and interleukin(IL)-lbeta, and the key
      molecules in p38MAPK signaling pathway including p38 mitogenactivated protein
      kinase (MAPK), phosphorylated p38 (p-p38MAPK) and transforming growth factor(TGF)
      beta1 were investigated respectively. RESULT: GTW not only ameliorated the
      general state of health and body weight,but also attenuated UAlb,
      glomerulosclerosis, the infiltration of glomerular ED1 + cells and the protein
      expressions of TNF-alpha, IL-1beta, p-p38MAPK and TGF-beta1 in the kidney in DN
      model rats. CONCLUSION: By means of DN model rats, we demonstrated that GTW has
      the protective effect on renal inflammatory damage in vivo via inhibiting
      inflammatory cells infiltration and inflammatory cytokines expression.
      Furthermore, GTW could improve renal inflammatory lesion through down-regulating
      the expressions of the key signaling molecules in p38MAPK pathway such as p
      p38MAPK and TGF-beta1 ,and inhibiting the activation of p38MAPK signaling in the
      kidney.

PMID- 25775777
TI  - [Effects and mechanisms of huangkui capsule ameliorating renal fibrosis in
      diabetic nephropathy rats via inhibiting oxidative stress and p38MAPK signaling
      pathway activity in kidney].
AB  - OBJECTIVE: To demonstrate the effects and mechanisms of Huangkui capsule (HKC) on
      renal fibrosis in rats with diabetic nephropathy (DN). METHOD: Rats were randomly
      divided into 5 groups, the sham-operated group (Sham group, n = 5), the vehicle
      given group (Vehicle group, n = 7), the low dose of HKC-treated group (L-HKC
      group, n = 7), the high dose of HKC-treated group (H-HKC group, n = 7) and the
      lipoic acid (LA)-treated group (LA group, n = 7). DN models were induced by
      intraperitoneal injection of streptozotocin (STZ,35 mg x kg(-1)) twice and
      unilateral nephrectomy. After models were successfully established, the rats in
      HKC and LA groups were daily administrated with HKC suspensions (0.75, 2 g x kg(
      1)) or LA suspensions (60 mg x kg(-1)) respectively, and at the same time, the
      rats in Vehicle group were daily administrated with distilled water (2 mL) for 8
      weeks. All rats were sacrificed at the end of week 8 to collect blood and renal
      tissues. UAlb, renal function, renal fibrotic morphologic characteristics, as
      well as oxidative stress (OS)-related markers, the protein expressions of the key
      signaling molecules in p38 mitogen-activated protein kinase (p38MAPK) signaling
      pathway, fibrogenic cytokines and inflammatory factors were examined
      respectively. RESULT: HKC, similar to LA, improved the general state of health,
      body weight, UAlb, BUN, UA and Alb in DN model rats. Of note, renal fibrosis was
      ameliorated in HKC groups,especially in H-HKC group which was better than that in
      LA group. In addition, HKC not only improved the main indexes of OS in the kidney
      like LA, but also down-regulated the protein expressions of phosphorylated
      p38MAPK (p-p38MAPK), transforming growth factor (TGF)-beta1 and tumor necrosis
      factor(TNF)-alpha in the kidney, whereas, LA only decreased the protein
      expression of TNF-alpha in the kidney in DN model rats. CONCLUSION: HKC, similar
      to LA, has the actions of anti-OS in vivo. Moreover, HKC could attenuate renal
      fibrosis by suppressing the activation of p38MAPK signaling pathway and the
      protein expressions of fibrogenic cytokines and inflammatory factors in the
      kidney in DN model rats, which is different from LA.

PMID- 25775778
TI  - [Rapid identification of six chemical constituents in Guizhi Fuling capsule by
      DART-Q-TOF-MS].
AB  - In order to establish a rapid method for identifying six constituents in Guizhi
      Fuling capsule, Q-TOF with DART ion source was used to perform the direct
      analysis of compounds in Guizhi Fuling capsule. The DART sampler delivery rate
      was 0.2 mm s(-1). The temperature of helium gas of DART was 450 degrees C. The
      capillary voltage was kept at 1 000 V. The temperature of the drying gas of
      Agilent 6538 Q-TOF MS was set at 350 degrees C. The flow rate of the drying gas
      of MS was set at 3.5 L x min(-1). The MS scan range was m/z 50-1 000. Based on
      accurate mass measurements and the elemental compositions of the product ions and
      fragmentation patterns of reference conpounds, six components, amygdalin,
      paeonol, paeoniflorin, cinnamic acids, gallic acid, benzoic acid were identified
      rapidly. The method can rapidly identify six chemical constituents in three batch
      of Guizhi Fuling capsule. The DART-Q-TOF-MS method is simple, rapid and specific
      and it can be used for rapid identification and characterization of compounds in
      traditional Chinese medicines.

PMID- 25775779
TI  - [Analysis methodology of multi element in four herbs of guizhi fuling capsules].
AB  - This paper was focused on establishing a ICP-MS method with microwave digestion
      for simultaneous determination of lead, copper, arsenic, cadmium, mercury,
      magnesium, manganese, nickel, thallium in cassia tuckahoe capsule and its five
      raw herbal materials. Internal standard method was adopted to reduce matrix
      effect and other interference effects. The method established was shown to be
      simple with high sensitivity, strong specificity and good reproducibility. Linear
      relationship is good as R2 >= 0.999 3 while the average recovery was among 75.84%
      - 118.9%. The detection limit was 0.016 - 4.593 MUg x L(-1). Data in this paper
      provided the basis for control of deleterious element in Guizhi Fuling capsules,
      and further more it was with referencing values for control of deleterious
      element in other crude drug.

PMID- 25775780
TI  - [Quality evaluation of guizhi fuling capsule using self-control method of
      reference Chinese medicine preparation].
AB  - Taking guizhi fuling capsule (GZFL) for instance, a new method about reference
      Chinese medicine preparation which was used as standard substance for the quality
      evaluation of complex Chinese medicine preparation by the fingerprint of
      reference preparation instead of standard fingerprint was proposed. It could
      eliminate the errors from different instruments, chromatographic columns and
      solve the problem of similarity matching in the absence of standard fingerprint.
      The qualification of reference GZFL was evaluated according to the quality
      control method of GZFL from Chinese Pharmacopoeia. Then multiple batches of GZFL
      were estimated, taking fingerprint of reference preparation and standard
      fingerprint as references, respectively, at different instruments and
      chromatographic columns. Finally, the packaging and expiration date for reference
      GZFL were confirmed according to the results of stability investigation. The
      results indicated that the fingerprint of reference GZFL could be used to assess
      the quality of GZFL better than standard fingerprint. The data of accelerated
      stability and long-term stability test demonstrated that reference GZFL was
      stable in the conditions of double blister package. Therefore, reference GZFL can
      be used as standard substance in quality control of GZFL.

PMID- 25775781
TI  - [Study on HPLC fingerprint of triterpene acids in different medicinal parts of
      Poria].
AB  - OBJECTIVE: To establish an analytical method for the fingerprint of triterpenoid
      constituents of Poria by HPLC and compare the fingerprints of different medicinal
      parts of Poria in order to provide basis for controlling Poria quality. METHOD:
      The HPLC chromatographic conditions were Waters Symmetry C18 column (4.6 mm x 250
      mm, 5 MUm), 0.1% phosphoric acid (A) and acetonitrile (B) as gradient mobile
      phases, flow rate being 1.0 mL x min(-1), column temperature at 30 degrees C, The
      detection wavelength was set at 210 nm; The cluster analysis was carried on by
      SPSS 15.0. RESULT: The HPLC fingerprints of triterpenoid constituents of Poria
      were set up. There were 16 common peaks in different medicinal parts. The results
      of method validation met technical requirement of fingerprints; Triterpenoid
      constituents in White Poria and Poria cum Radix Pini were different from Poria.
      The content of pachymic acid was the highest in Poria. The effect of habitat on
      the quality was no obvious difference. CONCLUSION: The method is stable,
      reliable, reproducible, and can be used as an effective means of Poria quality
      evaluation.

PMID- 25775782
TI  - [Effects of guizhi fuling capsule on sex hormone levels and breast issue
      morphology of mammary gland hyperplasia model rats].
AB  - OBJECTIVE: To research the effects of Guizhi Fuling capsule on sex hormones
      levels in blood serum and breast issue morphology of hyperplasia of mammary
      glands model rats. METHOD: The unpregnancy SD rat models of hyperplasia of
      mammary glands were established by injecting 0.5 mg x kg(-1) benzoate estradiol.
      After five weeks doses,the effects of Guizhi Fuling capsule 2.0, 1.0, 0.5 g x kg(
      1) and Rupixiao tablet 0.5 g x kg(-1) on the changes of papilla diameter, height
      and breast issue morphology of the naimal models were explored, and sex hormones
      levels in blood serum were measured. RESULT: Guizhi Fuling capsule can
      inhibitnipple swell, improve breast tissue morphology pathological profiles of
      the animal models, and decrease oestradiol (E2) level and increase progesterone
      (P) level in blood serum. CONCLUSION: These results suggested that Guizhi Fuling
      capsule could, improve mammary gland pathological profiles. Regulating sex
      hormone levels may be its important mechanism for treatment of hyperplasia of
      mammary glands.

PMID- 25775783
TI  - [Research progress of pretreatment of biological samples].
AB  - Suitable pretreatment of biological samples can truly reflect the role of law of
      the measured components played in the body and will provide experimental evidence
      for the studies on metabolic process, material basis of efficacy, mechanism of
      action, pharmacology, toxicology and the others. Biological samples include
      blood, urine, hair, tears, etc. There are also many samples processing methods,
      such as the direct protein precipitation, liquid-liquid extraction and solid
      phase extraction and so on. These methods could be used alone or combined.

PMID- 25775784
TI  - [Research progress on processed Chinese medicine in vivo].
AB  - Processed Chinese medicine is the core of traditional Chinese medicine (TCM)
      industry chain,which directly affects the clinical efficacy and. safety of
      Chinese patent medicine and clinical formula Decoction pieces. Studied the
      variation of effective substance in vivo Chinese medicine processing before and
      after processed, clarifying the effective substance and processing principle is a
      top priority of the development of Chinese medicine processing. The traditional
      research method chiefly focus on the variation about chemicals in vitro of
      processed Chinese medicine, it cannot reveal that the integrity and complexity of
      processed Chinese medicine efficacy changes, so the change process is the focus
      of future research in vivo on the base of effective substance of TCM This paper
      described the research on the base of effective substance of TCM and Processed
      Chinese medicine research status in vitro, discussed the analytical methods
      (plasma chemistry, pharmacokinetics, metabonomics) of the dynamic process in vivo
      about processed Chinese medicine, and pointed out development and related
      problems in process in vivo on the base of effective substance of TCM, which
      could provided research ideas and methods for in-depth interpretation of Chinese
      medicine processing mechanism.

PMID- 25775785
TI  - [Advances in research of chemical constituents and pharmacological activities of
      common used spices].
AB  - Spices have enjoyed a long history and a worldwide application. Of particular
      interest is the pharmaceutical value of spices in addition to its basic seasoning
      function in cooking. Concretely, equipped with complex chemical compositions,
      spices are of significant importance in pharmacologic actions, like antioxidant,
      antibacterial, antitumor, as well as therapeutical effects in gastrointestinal
      disorders and cardiovascular disease. Although increasing evidences in support of
      its distinct role in the medical field has recently reported, little information
      is available for substantive, thorough and sophisticated researches on its
      chemical constituents and pharmacological activities, especially mechanism of
      these actions. Therefore, in popular wave of studies directed at a single spice,
      this review presents systematic studies on the chemical constituents and
      pharmacological activities associated with common used spices, together with
      current typical individual studies on functional mechanism, in order to pave the
      way for the exploitation and development of new medicines derived from the
      chemical compounds of spice (such as, piperine, curcumin, geniposide,
      cinnamaldehyde, cinnamic acid, linalool, estragole, perillaldehyde, syringic
      acid, crocin).

PMID- 25775786
TI  - [Advance in studies on anti-inflammatory and immunoregulatory monomers of
      Tripterygium wilfordii].
AB  - Tripterygium wilfordii has complex chemical components. To study and summarize
      the advance in studies on the anti-inflammatory and immunoregulatory activities
      and toxicology of known monomers of T. wilfordii, the pertinent literatures
      related to the studies on the pharmacology, toxicology and pharmacokinetics of T.
      wilfordii over past 30 years were searched. According to the findings, more than
      ten anti-inflammatory and immunoregulatory monomers were found in T. wilfordii.
      The pharmacology and toxicology of wilforidine, triptolidenol, triptonide,
      demethylzeylasteral shall be further studied.

PMID- 25775787
TI  - [Research progress on antitumor effects and mechanisms of phellinus].
AB  - Phellinus is a kind of rare medicinal fungus that has a variety of physiological
      activities include anti-cancer, anti-liver fibrosisa, antioxidant and so on.
      Phellinus contains polysaccharides, steroids, terpenoids, flavonoids, pyrone,
      furan, alkaloids and other substances. Polysaccharide extracts of phellinus
      showed obvious antitumor effect and has been a hot research field in recent
      years. It was also found other extracts of phellinus such as ethyl acetate
      extract exhibited anticancer activity. Thus, the antitumor effect of different
      extract, especially the anti-cancer mechanism were discussed in this review.

PMID- 25775788
TI  - [Fungal composition in massa medicata fermentata based on culture dependent
      method and independent PCR-SSCP technique].
AB  - OBJECTIVE: To analyze the fungal composition in Massa Medicata Fermentata based
      on culture dependent method and independent PCR-SSCP technique. METHOD: Fungi
      were directly isolated from Massa Medicata Fermentata samples. The obtained
      strains were identified according to morphology and DNA sequence. Meanwhile the
      total fungal DNA was extracted from Massa Medicata Fermentata samples, the
      cultural independent PCR-SSCP technique based on beta-tubulin gene were used to
      identify the mycobiota. RESULT: According to cultural method, Aspergillus flavus
      and Rhizopus oryzae were present in Massa Medicata Fermentata samples, while A.
      flavus and A. niger were present in fried Massa Medicata Fermentata samples. In
      contrast, 5 species were obtained by PCR-SSCP technique, A. flavus was overlapped
      with fungal taxa derived from culture dependent method; A. ambiguu and A. s
      ivoriensis were dominant with relative abundance of 57% and 35% respectively,
      while the relative abundance of A. flavus was as low as 4%. None species was
      obtained from fried Massa Medicata Fermentata samples. CONCLUSION: PCR-SSCP based
      on beta-tubulin gene could distinguish fungi into species, culture dependent
      method combined with culture independent method could better understand the
      fungal composition associated with Massa Medicata Fermentata fermentation.

PMID- 25775789
TI  - [Cloning and bioinformatics analysis of ent-kaurene oxidase synthase gene in
      Salvia miltiorrhiza].
AB  - Based on the transcriptome database of Salvia miltiorrhiza, specific primers were
      designed to clone a full-length cDNA of ent-kaurene oxidase synthase (SmKOL)
      using the RACE strategy. ORF Finder was used to find the open reading frame of
      SmKOL cDNA, and ClustalW has been performed to analysis the multiple amino acid
      sequence alignment. Phylogenetic tree has been constructed using MEGA 5.1. The
      transcription level of SmKOL from the hairy roots induced by elicitor methyl
      jasmonate (MeJA) was qualifiedby real-time quantitative PCR. The full length of
      SmKOL cDNA was of 1 884 bp nucleotides encoding 519 amino acids. The molecular
      weight of the SmKOL protein was about 58.88 kDa with isoelectric point (pI) of
      7.62. Results of real-time quantitative PCR analyses indicated that the level of
      SmKOL mRNA expression in hairy roots was increased by elicitor oMeJA, and reached
      maximum in 36 h. The full-length cDNA of SmKOL was cloned from S. miltiorrhiza
      hairy root, which provides a target gene for further studies of its function,
      gibberellin biosynthesis and regulation of secondary metabolites.

PMID- 25775790
TI  - [Seed quality test methods of Paeonia suffruticosa].
AB  - In order to optimize the testing methods for Paeonia suffruticosa seed quality,
      and provide basis for establishing seed testing rules and seed quality standard
      of P. suffruticosa. The seed quality of P. suffruticosa from different producing
      areas was measured based on the related seed testing regulations. The seed
      testing methods for quality items of P. suffruticosa was established
      preliminarily. The samples weight of P. suffruticosa was at least 7 000 g for
      purity analysis and was at least 700 g for test. The phenotypic observation and
      size measurement were used for authenticity testing. The 1 000-seed weight was
      determined by 100-seed method, and the water content was carried out by low
      temperature drying method (10 hours). After soaking in distilled water for 24 h,
      the seeds was treated with different temperature stratifications of day and night
      (25 degrees C/20 degrees C, day/night) in the dark for 60 d. After soaking in the
      liquor of GA3 300 mg x L(-1) for 24 h, the P. suffruticos seeds were cultured in
      wet sand at 15 degrees C for 12-60 days for germination testing. Seed viability
      was tested by TlC method.

PMID- 25775791
TI  - [Identification of peucedani radix, peucedani decursivi radix and its adulterants
      using ITS2 sequence].
AB  - In order to identify Peucedani Radix, Peucedani Decursivi Radix and their
      adulterants, the internal transcribed spacer 2 (ITS2) regions of Peucedani Radix,
      Peucedani Decursivi Radix and their adulterants were amplified and
      bidirectionally sequenced based on the Principles for Molecular Identification of
      Traditional Chinese Materia Medica Using DNA Barcoding, which has been
      promulgated by Chinese Pharmacopoeia Commission. Sequences were analyzed and
      assembled by Codon Code Aligner V3. 7.1. The relevant data were analyzed by MEGA
      5. 0. Species identification analyses were performed by using the nearest
      distance methods and neighbor-joining (NJ) methods. The result showed that the
      ITS2 sequence lengths of Peucedani Radix were 229-230 bp and the average intra
      specific genetic distances were 0.005. The ITS2 sequence lengths of Peucedani
      Decursivi Radix were 227 bp and the sequences contained no variation site. The
      average inter-specific K2P genetic distance of Peucedani Radix, Peucedani
      Decursivi Radix and their adulterants species were 0.044 and 0.065 respectively.
      The minimum inter-specific divergence is larger than the maximum intra-specific
      divergence of Peucedani Decursivi Radix. The nearest distance methods and NJ
      trees results indicated that Peucedani Radix, Peucedani Decursivi Radix and their
      adulterants species could be identification clearly. The ITS2 regions can stably
      and accurately distinguish Peucedani Radix, Peucedani Decursivi Radix and their
      adulterants.

PMID- 25775792
TI  - [Procedure of seed quality testing and seed grading standard of Prunus humilis].
AB  - So far there exists no corresponding quality test procedures and grading
      standards for the seed of Prunus humilis, which is one of the important source of
      base of semen pruni. Therefor we set up test procedures that are adapt to
      characteristics of the P. humilis seed through the study of the test of sampling,
      seed purity, thousand-grain weight, seed moisture, seed viability and germination
      percentage. 50 cases of seed specimens of P. humilis tested. The related data
      were analyzed by cluster analysis. Through this research, the seed quality test
      procedure was developed, and the seed quality grading standard was formulated.
      The seed quality of each grade should meet the following requirements: for first
      grade seeds, germination percentage >= 68%, thousand-grain weight 383 g, purity
      >= 93%, seed moisture <= 5%; for second grade seeds, germination percentage >=
      26%, thousand-grain weight >= 266 g, purity >= 73%, seed moisture <=9%; for third
      grade seeds, germination percentage >= 10%, purity >= 50%, thousand-grain weight
      >= 08 g, seed moisture <= 13%.

PMID- 25775793
TI  - [Breeding on eight strains of Pseudostellaria heterophylla based on phenotypic
      traits and quality in Guizhou province].
AB  - OBJECTIVE: To provide new germplasm materials for breeding new varieties of
      Pseudostellaria heterophylla. METHOD: The method of single plant selection was
      adopted, with the comparative experiments being carried out under the same
      conditions in Shibing county. The 8 plants of Shibing SB-4 were compared
      respectively with factor analysis for 27 phenotypic traits and 8 yield traits,
      and single factor variance analysis for the contents of polysaccharides. RESULT:
      Using factor analysis, 27 phenotypic traits were classified into 7 principal
      divisors and 8 yield traits were simplified into 3 principal divisors. The 4
      strains of P. heterophylla, ZT-01, ZT-02, ZT-06 and ZT-07, performed better than
      others in the phenotypic traits, and ZT-01, ZT-02, ZT-03 and ZT-07 in the yield
      traits. The contents of polysaccharides of ZT-01, ZT-02, ZT-05 and ZT-08 showed
      significantly higher value. CONCLUSION: There is significant difference among the
      8 strains of P. heterophylla in phenotypic traits, yield traits and quality
      traits, making it possible to select certain strains for different purposes. ZT
      01 and ZT-02 can be breaded further. ZT-06 and ZT-07 were used as ornamental
      cultivars for its great phenotypic traits. ZT-03 with good resistance and high
      yield was taken as resistant variety, and ZT-05 would face next selection on the
      basis of its high content of polysaccharide.

PMID- 25775794
TI  - [Effect of fibrous root extract of Coptis chinensis on soil microbes and enzyme
      activities].
AB  - Coptis chinensis is widely used as Chinese medicine herbs and serious soil
      problems occur after continual cultivation of this medicinal plant. In the preset
      experiment, fibrous root extract of C. chinensis (REC) was added into soil to
      study the effect of REC on microbes and enzyme activity in soil. The results
      showed that both bacteria and actinomycetes decreased by about 2 times in
      contrast to fungi, which increased by about 3 folds. Phosphorus bacteria,
      potassium bacteria, azotobacter, ammonia bacteria, and nitrifying bacteria were
      also reduced significantly by REC, suggesting the inhibition of nitrogen
      biofixation and supply, mobilization of phosphorus and potassium, ad plant growth
      promotion as REC added into soil. There were multiple influences of REC on soil
      enzyme activities. Invertase activity was stimulated, while urease was inhibited
      and dehydrogenase unchanged by REC, indicating the interference of biochemical
      reactions in soil. In addition, type and total content of phosphorus lipid fatty
      acids (PLFAs) , the signature of microbes, decreased while the ratio of bacterium
      to fungus PLFAs increased as REC increased in soil, which suggested that fungi
      increased relatively with bacteria decreased thereby leading to easy occurrence
      of crop fungus diseases following cultivation of C. chinensis. The decrease in
      diversity and evenness indexes of microbial community in soil by REC indicated
      soil ecosystem deterioration and reduction of microbial groups and densities in
      soil. Therefore, allelopathic chemicals released from the roots of C. chinensis
      could change microbial community structure and resulted in serious soil problems
      by continual cropping of this medicinal plant.

PMID- 25775795
TI  - [Protoplasts isolation, purification and plant regeneration of Pinellia cordata].
AB  - The main factors which affected the isolation, purification and cultivation of
      Pinellia cordata protoplasts from leaves were studied. The results indicated that
      the optimum enzyme solution for P. cordata leaves was 13% CPW + 1.0% Cellulose
      +0.1% Pectolase, at pH 6.0, temperature (25-28 degrees C ) for 4 h. The sucrose
      density gradient centrifugation was adopted to purificate the protoplasts
      collected, when 25% sucrose was used as mediator, centrifugating at 500 rpm for
      10 min. When the protoplasts were shallow liquid and liquid-solid double layer
      cultured on the medium of MS + 0.5 mg x L(-1) 6-BA + 0.25 mg x L(-1) NAA + 13%
      mannitol at the density of 2.5 x 104 protoplasts/mL, or fed and nursed cultured
      at the density of 100-500 protoplasts/mL, cell division could be observed for 3
      days; granular calli appeared for 30 days. Calli was proliferated on the medium
      of MS + 0.5 mg x L(-1) 6-BA + 0.25 mg x L(-1) NAA solidified by 0.55% agar, and
      differentiated and regenerated after 5-6 months. Plant generation of P. cordata
      is successfully established.

PMID- 25775796
TI  - [Effects of Pb2+ stress on seed germination & seedling growth of Rabdosia
      rubescens].
AB  - The seeds of Rabdosia rubescens were as the materials to research the impacts of
      different lead (Pb2+) concentrations(0, 135, 270, 540, 1 080 mg x L(-1)) on seed
      germination and seedling growth. The results show that: Low concentration of lead
      had no obvious effect on early germination of the seed, the germination vigor and
      germination speed were lightly higher but not significantly differed at the level
      of Pb concentration 135 mg x L(-1) with control group; Mid-high concentration of
      Pb solution (270-1 080 mg x L(-1)) significantly inhibited the seed germination
      and seedling growth, which reduced the seed germination rate, germination vigor,
      germination index, embryo root length and shoot length, growth index with
      increasing of Pb concentrations. There was a inhibitory effect on embryo shoot
      length and root length at mid-high lead concentrations stress, and stronger
      inhibitory effect on root , which was more sensitive than shoot to Pb stress(P <
      0.05). Pb bioaccumulation coefficient (BC) was 0.76-2.59, increased with
      concentration of Pb; Pb enrichment in seedling mainly caused the growth
      inhibition. The fitting model predictive analyses show, the critical
      concentration of Pb, which causes the germination rate and biomass fresh weight
      reducing 10%, is 195.18, 101.65 mg x L(-1).

PMID- 25775797
TI  - [Effects of tree species on polysaccharides content of epiphytic Dendrobium
      officinale].
AB  - To reveals the effects of tree species on polysaccharides content of epiphytic
      Dendrobium officinale. The polysaccharides content of D. officinale attached to
      living tress in wild or stumps in bionic-facility was determined by phenol
      sulfuric acid method. There were extremely significant differences of
      polysaccharides content of D. officinale attached to different tree species, but
      the differences had no relationship with the form and nutrition of barks. The
      polysaccharides content of D. officinale mainly affected by the light intensity
      of environment, so reasonable illumination favored the accumulation of
      polysaccharides. Various polysaccharides content of D. officinal from different
      attached trees is due to the difference of light regulation, but not the form and
      nutrition of barks.

PMID- 25775798
TI  - [Triterpenes constituents from male flowers of Eucommia ulmoides].
AB  - Nine triterpenes compounds were isolated from the male flowers of Eucommia
      ulmoides by recrystallization and chromatographic techniques over silica gel,
      Sephadex LH-20, and RP-18 gel. Their chemical structures were identified on the
      basis of spectral analysis and as 3-oxo-12-en-ursane-28-O-alpha-L
      arabinofuranosyl (1 --> 6) -beta-D-glucopyranoside (1), 2alpha, 3beta
      dihydroxyurs-12-en-28-oic acid(28 --> 1) -beta-D-glucopyranosyl ester (2),
      ursolic acid (3), alpha-amyrin (4), uvaol (5), ursolic acid acetate (6), 3-O
      acetate oleanoic acid (7), betulinic acid (8), and betulinol (9). Compound 1 was
      a new compound, and compounds 2, 4-7 were isolated from the Eucommiu genus for
      the first time. Cytotoxic activity was tested for all the compounds against K562
      and HepG2 cells. The results showed that only compound 3, exhibited cytotoxic
      activity.

PMID- 25775799
TI  - [Anthraquinones and triterpenoids from roots of Knoxia roxburghii].
AB  - Nine compounds were isolated from an ethanol extract of the roots of K.
      roxburghii by using a combination of various chromatographic techniques including
      column chromatography over silica gel, MCI gel, Sephadex LH-20, and reversed
      phase HPLC. On the basis of physical-chemical properties and spectroscopic data
      analysis, their structures were identified as munjistin (1), 1-methoxy-3,6
      dihydroxy-2-hydroxymethyl-9,10-anthraquinone (2), 1,2,3-trihydroxy-9,10
      anthraquinone (3), arjunolic acid (4), hyptatic acid-A (5), hyptatic acid-B (6),
      2alpha,3beta,24-trihydroxyurs-12-en-28-oic acid (7), 2alpha,3beta,23
      trihydroxyurs-12-en-28-oic acid (8), and daucosterol (9). Compounds 1-9 were
      obtained from this genus for the first time.

PMID- 25775800
TI  - [Study on three different species tibetan medicine sea buckthorn by 1H-NMR-based
      metabonomics].
AB  - The 1H-NMR fingerprints of three different species tibetan medicine sea buckthorn
      were established by 1H-HMR metabolomics to find out different motablism which
      could provide a new method for the quality evaluation of sea buckthorn. The
      obtained free induction decay (FID) signal will be imported into MestReNova
      software and into divide segments. The data will be normalized and processed by
      principal component analysis and.partial least squares discriminant analysis to
      perform pattern recognition. The results showed that 25 metabolites belonging to
      different chemical types were detected from sea buckthorn,including flavonoids,
      triterpenoids, amino acids, carbohydrates, fatty acids, etc. PCA and PLS-DA
      analysis showed three different varietiest of sea buckthorn that can be clearly
      separated by the content of L-quebrachitol, malic acid and some unidentified
      sugars, which can be used as the differences metabolites of three species of sea
      buckthorn. 1H-NMR-based metabonomies method had a holistic characteristic with
      sample preparation and handling. The results of this study can offer an important
      reference for the species identification and quality control of sea buckthorn.

PMID- 25775801
TI  - [Research on UPLC-PDA fingerprint of andrographis paniculata and quantitative
      determination of 4 major constituents].
AB  - Andrographis paniculata from different parts and origins were analyzed by UPLC
      PDA fingerprint to provide refererice for related preparation technology. Using
      the peak of andrographolide as reference, 27 common peaks were identified, and
      digitized UPLC-PDA fingerprints for 23 batches of andrographis paniculata were
      established in this research. Principal component analysis (PCA) was carried out
      after feature extraction. The contents of andrographolide, neoandrographolide,
      deoxyandrographolide, dehydroandrographolide were determined by external standard
      method. The Plackett-Burman design combined with pareto chart was used to analyze
      the factors influencing the robustness of the method. It was found that the
      medicinal part has a more remarkable influence on the quality of andrographis
      paniculata than the origin. The contents of the 4 lactones the differ greatly in
      the different parts of andrographis paniculata, and the pH of the mobile phase is
      an important factor that influenced the robustness of the method.

PMID- 25775802
TI  - [Study on variation of main ingredients from spores and fruiting bodies of
      Ganoderma lucidum].
AB  - OBJECTIVE: To reveal the quality variation of polysaccharides, triterpenoids and
      proteins in spores and fruiting bodies of Ganoderma lucidum from producing areas,
      different varieties, harvesting parts and periods, and wall-breaking treatments.
      METHOD: Spores and fruiting bodies from varieties of Longzhi No. 1 and Hunong No.
      1 were collected as test samples, together with wall-broken spores sold in
      domestic main producing areas. The anthrone-sulfuric acid colorimetric method was
      used to determine the content of total polysaccharides. The vanillin-glacial
      acetic acid-perchloric acid colorimetric method was used to determine the content
      of total triterpenoids. The Lowry method was used to determine the content of
      total proteins. RESULT: The content ranges of total polysaccharides, total
      triterpenoids, and total proteins from 6 domestic main producing areas were 0.40%
      - 2.25%, 1.36%-3.15% and 0.74% -1.91% respectively. The content ranges of total
      polysaccharides, triterpenoids, and proteins in the fruiting bodies from 2
      varieties cultured in Zhejiang were 0.25% -1.42%, 0.44% -1.42% and 1.82% -3.67%
      respectively. In addition, the ranges of samples from wall-unbroken spores were
      0.41% - 0.91%, 0.09% - 0.12%, 0.78% - 0.90% respectively and wall-broken spores
      are 1.03% - 2.25%, 1.89% - 3.15%, 0.96% - 1.04% respectively. CONCLUSION: There
      are significant differences in the contents of main chemical ingredients of wall
      broken G. lucidum spores saled in the markets. The samples from Zhejiang contain
      high content of total polysaccharides and triterpenoids, and samples from Fujian
      contains more proteins. Between the 2 major varieties cultured in Zhejiang,
      Longzhi No. 1 contains higher content of triterpenoids, but Hunong No. 1 has more
      polysaccharides. Contents of triterpenoids and polysaccharides from wall-broken
      spores are much higher than those of fruiting bodies. The stipes from fruiting
      bodies contains more polysaccharides than those of the pileus, while the
      triterpenoids contents are higher in the pileus than stipes. The pileus and
      stipes collected in the second year contain higher content of polysaccharides
      than the first year's samples, but the contents of triterpenoids are lower. Wall
      breaking treatment would significantly improve the extraction and dissolution
      rate of total triterpenoids and polysaccharides.

PMID- 25775803
TI  - [Effect of methyl jasmonate on salidroside and polysaccharide accumulation in
      Rhodiola sachalinensis callus].
AB  - OBJECTIVE: To provide a new material for producing the Rhodiolasachalinensis
      products, the effect of methyl jasmonate (MeJA) on callus biomass and effective
      compound accumulation of Rhodiolasachalinensis was studied. METHOD: The calluses
      cultured in 3 L-air lift balloon type bioreactor were treated with MeJA after 20
      d of bioreactor culture and the effect of MeJA concentration and treatment days
      on callus biomass, salidroside or polysaccharide accumulation and superoxide
      dismutase (SOD) and peroxidase (POD) activities were investigated. RESULT: The
      callus biomass was not significantly different after MeJA treatment (125) for 0-6
      d but obviously decreased after 6 d treatment. The maximum salidroside or
      polysaccharide contents and SOD or POD activities were found after 4 d treatment
      of MeJA. MeJA concentration significantly affected callus biomass and effective
      compound accumulation, biomass decreased at MeJA concentrations higher than 125
      MUmol x L(-1). However, the effective compound contents were determined at higher
      MeJA concentration, and the highest salidroside and polysaccharide accumulation
      was found at 225 and 275 MUmol x L(-1) MeJA, respectively and the maximum SOD and
      POD activities was found at 225 MUmol x L(-1) MeJA. The effective compound
      contents in callus were compared with field-grown plants. Salidroside contents in
      calluses were 1.1-fold and 2. 4-fold more than in plant roots and stem or leave,
      respectively. Polysaccharide content in calluses were 3. 6-fold and 8.0-fold more
      than in plant roots and stem or leave, respectively. CONCLUSION: Salidorside and
      polysaccharide in Rhodiolasachalinensiscalluses improved by MeJA treatment, 225
      MUmol x L(-1) MeJA and 4 d treatment were optimal. The effective compound
      contents in callus were obviously higher than in field-grown plants. Therefore,
      bioreactor culture is efficient for obtaining mass effective compounds of
      Rhodiolasachalinensis by culturing calluses. This method could provide an
      alternative material source for production of Rhodiolasachalinensis products.

PMID- 25775804
TI  - [Stability study in biological samples and metabolites analysis of astragaloside
      IV in rat intestinal bacteria in vitro].
AB  - To figure out the stability and intestinal bacteria metabolites of rats in vitro
      of astragaloside IV ( AST), this research was done to explore the stability of
      AST in the artificial gastric juice. artificial intestinal juice and rat liver
      homogenate and the metabolism in rat intestinal in vitro. HPLC was used to
      calculate the remaining rate of AST in biological samples by measuring the
      content of AST, while metabolites were determined by combining the methods of
      TLC, HPLC and LC-MS/MS. It turned out that AST was difficult to metabolize in the
      artificial gastric juice, artificial intestinal juice and rat liver. Also, the
      metabolic pathway of AST was stepped by deglycosylation. Firstly, AST was
      converted to its secondary etabolites (6-O-beta-D-glucopyranosyl-
      cycloastragenol, CMG) by removal of xylose moiety at C-3, then transformed into
      cycloastragenol (CAG) after hydrolytic removal of the glucose moiety at C-6. All
      the results suggested that the metabolism of AST in vivo occurs mainly in the
      intestinal by hydrolysis of glycosyl. In conclusion, hydrolysis of intestinal
      flora is the main reason that AST metabolizes.

PMID- 25775805
TI  - [Enlightenment of drug application and evaluation procedures of medicines
      registered (listed) in Australia on studies of new traditional Chinese
      medicines].
AB  - Modern and international studies on new traditional Chinese medicines are the
      main trend of the development of traditional Chinese medicines at present. In
      Australia, new traditional Chinese medicines refer to complementary medicines,
      which are mainly registered and launched as listed medicines. The application
      documents of registered (listed) medicines in Australia mainly cover detailed
      description of active pharmaceutical ingredients, pharmacological and
      toxicological studies, dosage form and adverse effects. Each part has detailed
      specifications and instructions, which helps ensure that applicants could
      accurately understand the requirements in application for registering (listing)
      medicines, and provides very important reference to the studies and development
      of new traditional Chinese medicines in China.

PMID- 25775806
TI  - [Application of multivariate statistical analysis and thinking in quality control
      of Chinese medicine].
AB  - The study of quality control of Chinese medicine has always been the hot and the
      difficulty spot of the development of traditional Chinese medicine (TCM), which
      is also one of the key problems restricting the modernization and
      internationalization of Chinese medicine. Multivariate statistical analysis is an
      analytical method which is suitable for the analysis of characteristics of TCM.
      It has been used widely in the study of quality control of TCM. Multivariate
      Statistical analysis was used for multivariate indicators and variables that
      appeared in the study of quality control and had certain correlation between each
      other, to find out the hidden law or the relationship between the data can be
      found,.which could apply to serve the decision-making and realize the effective
      quality evaluation of TCM. In this paper, the application of multivariate
      statistical analysis in the quality control of Chinese medicine was summarized,
      which could provided the basis for its further study.

PMID- 25775807
TI  - [Establishment of prescription research technology system in Chinese medicine
      secondary exploitation based on "component structure" theory].
AB  - Chinese medicine prescriptions are the wisdom outcomes of traditional Chinese
      medicine (TCM) clinical treatment determinations which based on differentiation
      of symptoms and signs. Chinese medicine prescriptions are also the basis of
      secondary exploitation of TCM. The study on prescription helps to understand the
      material basis of its efficacy, pharmacological mechanism, which is an important
      guarantee for the modernization of traditional Chinese medicine. Currently, there
      is not yet dissertation n the method and technology system of basic research on
      the prescription of Chinese medicine. This paper focuses on how to build an
      effective system of prescription research technology. Based on "component
      structure" theory, a technology system contained four-step method that
      "prescription analysis, the material basis screening, the material basis of
      analysis and optimization and verify" was proposed. The technology system
      analyzes the material basis of the three levels such as Chinese medicine pieces,
      constituents and the compounds which could respect the overall efficacy of
      Chinese medicine. Ideas of prescription optimization, remodeling are introduced
      into the system. The technology system is the combination of the existing
      research and associates with new techniques and methods, which used for explore
      the research thought suitable for material basis research and prescription
      remodeling. The system provides a reference for the secondary development of
      traditional Chinese medicine, and industrial upgrading.

PMID- 25775808
TI  - [Treatment of asthma in Poland by primary care physicians--results of PulmoScreen
      study].
AB  - INTRODUCTION: Proper treatment of asthma patients is crucial for long-term
      control of the disease. OBJECTIVE: The aim of the study was to evaluate the
      treatment of adult asthma patients by primary care physicians in the light of
      international GINA guidelines. MATERIAL AND METHOD: The cross-sectional study
      included a representative sample of 1852 general practitioners (GPs) who were
      asked to complete questionnaires on the diagnosis and treatment often consecutive
      patients with asthma who are under their care. RESULTS: Altogether 1250 GPs
      provided information about 10,981patients. During the entire duration of the
      disease 50.9% were ever treated by systemic corticosteroids. In the current
      treatment of asthma inhaled steroids were used in 78.8% of cases, oral steroids
      in 5.8%, intravenous steroids in 1.3% and intramuscular steroids in 0.7% of
      patients. SABA were used in 63.1% of patients, LABA in 57.1%, methylxanthine in
      25.1%, leukotriene modifiers in 21.1%, anticholinergics drugs in 15.5%, cromones
      in 1,9%, and antihistamines in 23.1% of adult patients with asthma. In 88.8%
      cases LABA treatment was combined with inhaled corticosteroids. In 83.8% of cases
      therapeutic regimens were in line with the GINA guidelines. CONCLUSIONS: There is
      a need for systematic educational activities addressed to primary care
      physicians.

PMID- 25775809
TI  - [Evaluation of the effectiveness of rehabilitation in patients after stroke with
      executive dysfunction].
AB  - INTRODUCTION: Executive dysfunction (DES) in the form of disturbances of
      conscious and flexible programming, organization and control of their own actions
      as part of the clinical picture of stroke. impairment of the executive mechanism
      may reduce the efficacy of treatment of patient. The aim of this study was to
      assess the impact of rehabilitation on improving executive functions in patients
      after stroke. MATERIAL AND METHODS: The study involved 90 patients after a
      stroke. The study group comprised 45 patients, resident in the Department of
      Rehabilitation and Physical Medicine USK of Medical University in Lodz, which was
      implemented in 5 week rehabilitation program including: kinesiotherapy,
      physiotherapy, speech therapy classes and psychological consultation and
      psychotherapy. The control group consisted of patients waiting for admission to
      the Department of Rehabilitation. The study was conducted twice: the first time,
      before the start of rehabilitation, the second time at the end of five weeks of
      the rehabilitation process. Executive functions were assessed by means of: Test
      of Wisconsin Card Sorting Test (WCST), Trail Making Test (TMT-A, TMT-B), Verbal
      Fluency Test (VFT). RESULTS: In patients after stroke rehabilitation in the
      hospital was significantly greater improvement in executive function compared to
      those rehabilitated in environmental conditions. CONCLUSIONS: Comprehensive
      rehabilitation in the hospital has a significant impact on improving executive
      functions in patients after stroke.

PMID- 25775810
TI  - [Secondary hemophagocytic syndromes].
AB  - Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening extreme whole body
      inflammatory state. It results from the pathological hyperactivation of the
      immune system, because of congenital or acquired abnormalities of cytotoxicity
      and NK or T cells. Uncontrolled stimulation of lymphocytes and macrophages lead
      to hypercytokinemia, organ infiltration by these cells and multiple organ
      failure. There are genetic HLH and secondary HLH, associated with infections,
      autoimmune disorders, malignancies. The frequency of the secondary form is
      difficult to estimate because of the wrong and difficult diagosis. The clinical
      course is often insidious and nonspecific. Symptoms are varied. The most
      important are: unremitting fever, hepatosplenomegaly. Generalized edema, rash,
      lymphadenopathy may occur. Liver failure, respiratory, circulatory and multiple
      organ failure could develop in a very short time. Most common abnormalities in
      additional tests are: cytopenias, hypofibrinogenaemia, hypertriglyceridaemia,
      hyperferritinaemia, hypertransaminasaemia, elevated parameters of inflammation
      (excepting lowering erythrocyte sedimentaion rate). Criteria for diagnosis and
      therapeutic protocols referto the genetic forms of HLH. Currently, there are no
      guidelines for secondary HLH. Diagnostic and therapeutic difficulties also arise
      from clinical picture, similar as in the systemic inflammatory response syndrome,
      sepsis, multiple organ dysfunction syndrome. We present the clinical
      presentation, diagnostic pitfalls and treatment of secondary HLH, based on a
      review of the current literature and our own observations.

PMID- 25775811
TI  - [Differential diagnosis of multiple sclerosis and autoimmune rheumatic diseases].
AB  - Multiple sclerosis (MS) is a progressive demyelinating-inflammatory disease of
      the central nervous system, probably of autoimmune etiology. Characteristic
      qualities include multifocal demyelination, which result in varied clinical
      pictures of the disease. MS must be differentiated from chronic or recurring
      diseases, as well as from those with multifocal neurological manifestations and
      multifocal lesions revealed in a MR scan. Particular signs may precede the
      development of the full-blown MS, but they may be initial manifestations of
      autoimmune disease such as systemic lupus, antiphospholipid syndrome, Behcet's
      disease or Sjogren's syndrome as well. Diagnosis is easier in the later stages
      due to appearance of characteristic manifestations, absent in the course of MS.
      Nevertheless, the mildly symptomatic nature of those diseases may lead to
      misdiagnosis, putting the patient at risk of an expensive and inefficient
      treatment, which may only exacerbate the symptoms. In many cases a long-term
      follow-up is necessary to confirm the diagnosis.

PMID- 25775812
TI  - [Ballism as a rare form of hyperkinetic movement disorder].
AB  - Hemiballism is a very rare movement disorderthat presents with involuntary
      unilateral flinging movements of the limbs. The movements are often violent and
      have wide amplitudes of motion. Hemichorea and hemiballism share pathophysiology
      and etiology, and commonly coexist in the same patient. Hemiballism was
      recognised as almost pathognomonic of a lesion in the contralateral subthalamic
      nucleus (body of Luys). Cerebrovascular diseases remain the most common etiology
      of ballistic movements. Interestingly, nowadays nonketotic hyperglycemiain
      elderly patients with diabetes mellitus is considered to be the second most
      common reported cause. Other more rare causes of hemiballism include
      encephalitis, cerebral toxoplasmosis (AIDS), multiple sclerosis, brain tumor
      (primary, metastatic) and metabolic disturbances. Prognosis is favorable for most
      patients with spontaneous resolution of clinical symptoms and dopamine receptor
      blocking drugs are highly effective.

PMID- 25775813
TI  - [Tiagabine--own experience in the refractory epilepsy treatment].
AB  - Tiagabine belongs to a new generation of antiepileptic drugs with a unique
      mechanism of action. It is well-absorbable from the gastrointestinal tract, has a
      linear pharmacokinetics, does not affect cognitive function and it interacts
      poorly with other antiepileptic drugs. Tiagabine is recommended for adults and
      children past 12 years of age with epilepsy, suffering from partial seizures,
      with and without secondary generalization. Following the period of a great
      enthusiasm as to the use of tiagabine, it was put aside, though unfairly,
      according to the author's own studies as well as the reports in current
      literature, it still has its place in the treatment of drug-resistant epilepsy.

PMID- 25775814
TI  - [Sexual dysfunctions and sexual satisfaction among multiple sclerosis patients].
AB  - Multiple sclerosis (MS) is a chronic inflammatory demyelinating disorder of the
      central nervous system with unclear pathogenesis. Among other clinical
      manifestations, sexual dysfunction (SD) is a common but still underreported and
      underdiagnosed symptom of the disorder. SD in MS patients may resultfrom a
      complex set of conditions and may be associated with multiple anatomic,
      physiologic, biologic, medical and psychological factors. SD arises primarily
      from lesions affecting the neural pathways involved in physiologic function. In
      addition, psychological factors, the side effects of medications and physical
      symptoms such as fatigue, muscular weakness, pain and concerns about bladder and
      bowel incontinence may also be involved. Since MS primarily affects young people,
      SD secondary to MS may have a great impact on quality of life.Thus, maintaining a
      healthy sexual life with MS is an important priority.

PMID- 25775815
TI  - [Clinical significance of pharmacogenetics in psychiatry].
AB  - One of the problems in the pharmacotherapy of mental disorders is among others a
      lack of appropriate response to treatment, which may be associated with
      ineffective therapy, adverse drug reactions and self medication. Participation of
      cytochrome P-450 isoenzymes (including CYP1A2, CYP2C19, CYP2D6, CYP3A4) in the
      metabolism of psychotropic drugs contributes to risk of adverse interactions,
      both in pharmacokinetic and pharmacodynamic phase. Pharmacogenetic studies may
      have an increasing importance in the field of improving both therapeutic
      effectiveness and safety of psychotropic drugs in treatment of mental disorders.

PMID- 25775816
TI  - [Endometriosis in adolescents].
AB  - The majority of adult women with endometriosis report that their symptoms started
      in adolescence. Early diagnosis and optimal treatment prevent disease progression
      and mitigate long-term morbidities, such as infertility and chronic pelvic pain.

PMID- 25775817
TI  - [Studies on the antimigraine action of Feverfew (Tanacetum parthenium (L.) Sch.
      Bip.)].
AB  - Feverfew was already known at the beginning of our era. In folk medicine,
      infusions from the leaves of Tanacetum parthenium were used in rheumatism, fever,
      and in migraine, menstrual pain, toothaches also digestive troubles, cough, or
      parasitic diseases. It has been proved that the biological activity of the plants
      resultsfrom the presence of the chemical compounds with different structures,
      including the the sesquiterpene lactones, which include partenolid, determining
      the antimigraine properties of plants. Research up to date on preclinical and
      clinical nature demonstrate the efficacy of plants in the prevention of migraine
      attacks. Based on the results can also conclude that the use of feverfew is safe
      and recorded side effects are mild and transient.

PMID- 25775818
TI  - [Biosimilars--opportunity or threat?].
AB  - Strong interest in biosimilars dates back several years. In the coming years the
      patent protection ends for subsequent biological drugs, including monoclonal
      antibodies. This paper organizes the most important facts related to the issue of
      biosimilars. A biosimilar is a biotherapeutic product which is similar in terms
      of quality, efficacy and safety to an already licensed reference biotherapeutic
      product'. It should be noted that biosimilars approved underthe current
      regulations of the European Medicines Agency (EMA) meet the stringent standards
      of safety, efficacy and immunogenicity. It is also important to realize that the
      biosimilar has the right to that name, if it is registered by regulatory
      authorities like EMA or FDA. One should not confuse biosimilar drugs with those
      which counterfeit or imitate. Clinical trials on the convertibility of innovative
      and biosimilar drugs are ongoing. Nevertheless,there is no regulatory framework
      and clear guidelines of conduct in this regard. In the near future, thanks to the
      registration of the first biosimilar monoclonal antibodies in rheumatology and
      gastroenterology the availability of biological treatment for patients should
      increase.

PMID- 25775819
TI  - [Infectious complications of stress urinary incontinence treatment with TVT
      procedure].
AB  - We present case report of 51-year-old female patient admitted to surgery ward
      because of presence of pyogenic discharge in perianal region since 7 months.
      Eighteen months earlierthe patient underwent stress urinary incontinence
      procedure with use of TVT synthetic implant. Diagnosis of wast, bilateral,
      composite vagino-perianal fistule was made. After carrying out four operations
      with two stage sling removal final postfistule wound healing was obtained.

PMID- 25775820
TI  - [A case of subclinical frontal lobe abscess as a complication of sinusitis].
AB  - Nowadays suppurative complications of sinusitis are uncommon in orderto
      widespread treatment with antibiotics. Intracranial complications include
      bacterial meningitis, encephalitis, brain abscess, epidural or subdural abscess
      and sinus thrombophlebitis.The 13-40% of all brain abscesses are sinogenic
      complications. The inflammation process spreads from sinuses by valveless diploic
      veins of the skull as thrombophlebitis or by direct extension of osteomyelitis.
      Jatrogenic, posttraumatic or natural fissures in bony walls can also take part in
      spreading the infection. Diagnostic process includes laryngological and
      neurological evaluation with the computer tomography scanning or magnetic
      resonance imaging. Patients with intracranial complications require broad
      spectrum antibiotic therapy and surgical treatment in orderto remove the origin
      of infection in the sinuses. For physicians they are always challenging
      conditions according to their significantly high mortality. The case of the 24
      year old patient with sinogenic brain abscess was shown in this paper. He
      neglected ambulatory treatment of chronic sinusitis because of lack of the
      medical insurance. After episode of losing the consciousness he was admitted to
      the ENT Department with headache, nausea, fever and dehydration. The diagnose was
      established based on laryngological and neurological examination and
      visualization of brain abscess on CT scans. He was treated by surgical
      intervention conducted by team of head and neck surgeons and neurosurgeons.
      Intensive antibiotic therapy with the Uffenorde operation of frontal sinuses and
      neurosurgical removal of the brain abscess was performed.The epidemiology,
      clinical course, diagnostic problems and therapy were described.

PMID- 25775821
TI  - [What changes were introduced by the new law concerning infectious diseases for
      patients with tuberculosis?].
AB  - On July 2012, the act on preventing and counteracting infections and infectious
      diseases in humans was amended. Many dchanges concemrning duties of physicians
      looking after patients with tuberculosis were proposed. Very important is the
      requirement of written certification by patients that they were notified by
      physician of the obligation of antituberculous treatment. It is also essential
      that the national sanitary inspector be notified as to which health-care
      institution the patient with tuberculosis was referred to for treatment, and also
      about an evasion of antituberculous therapy by the patient. Many paragraphs
      concernng the control of infectious diseases were formulated more precisely.

PMID- 25775822
TI  - [Induction of DNA damage in blood leucocytes and of cytogenetic injuries in bone
      marrow polychromatic erythrocytes in mice exposed to low-LET and high-LET
      radiation and in their progeny].
AB  - The present work was aimed at studying the molecular and cellular levels of the
      response of the hematopoietic system in mice and their progeny to the action of
      low-LET and high-LET radiation at different times after exposure. The damage to
      the genome at the molecular level was assessed by the comet assay in peripheral
      blood leucocytes, whereas at the cellular level it was estimated by means of the
      micronuclear test in the marrow cells, after exposure of mice to X-radiation of
      1, 3 and 5 Gy and to a high-LET low-intensity radiation at thedoses of 0.14 and
      0.35 Gy, as well as to a combined effect of these types of radiation. When
      accessing the level of the DNA damage to individual cells by the comet assay, we
      also used, apart from a commonly accepted parameter %TDNA, additional
      characteristics: the proportions of leucocytes with an intact and highly
      fragmented DNA. Using these parameters, we detected the changes characterizing
      the dynamics of the leukocyte population in mouse blood at different times after
      the action of X-ray and high-LET radiation. It was found that: (1) the DNA damage
      increases with the dose of high-LET radiation; (2) the level of damage in the
      progeny of the animals exposed to high-LET radiation does not differ from that in
      unirradiated animals both at the molecular and cytogenetic levels; and (3) a
      decrease in the radiosensitivity of the progeny of the mice exposed to high-LET
      radiation at a dose of 0.35 Gy makes itself evident only at the molecular level,
      which may point to the possible transgeneration transmission of genomic lesions.

PMID- 25775823
TI  - [Role of gene polymorphisms of phase II of xenobiotic biotransformation from
      glutathione-S-transferase and N-acetyltransferase families in susceptibility to
      lung cancer among Mayak workers].
AB  - An association between polymorphous (allelic) gene variants of phase II of
      enzymatic xenobiotic biotransformation (EXB) of multigene families of glutathione
      S-transferase (GSTs) GSTM1*0, GSTT1*0, GSTP1*B Ile105Val, and N-acetyltransferase
      (NAT) NAT2*6 590G>A, NAT2*5 481C>T, as well as lung cancer in Mayak workers
      exposed occupationally to prolonged external gamma-rays and internal alpha
      radiation from incorporated 239Pu was studied. Analysis of the population
      frequency of genotypes and alleles of the studied genes in the cohort of Mayak
      workers revealed their compliance with the Hardy-Weinberg principle and with the
      corresponding frequency in the European population. The study was based on the
      case-control method. A case-group consisted of 49 Mayal workers with a verified
      diagnosis of lung cancer. The mean total absorbed dose from external gamma-rays
      at the moment of diagnostics was 1.03 Gy; the mean total absorbed dose from
      internal alpha-radiation from incorporated 239Pu to lung was 0.35 Gy. Control
      consisted of 172 Mayak workers matched by the year of birth, gender, and age at
      the moment of employment at one of the main facilities with no lung cancer
      registered within the study period. No increase in the relative risk of lung
      cancer (odds ratio, OR) was revealed among the individuals with deletion variants
      of genes GSTM1*0 and GSTT1*0 (pp genotype, complete absence of gene products) as
      compared to the individuals with ww or wp genotype, which was determined in total
      for these genes (normal or partly decreased gene activity). An increase in OR of
      lung cancer in 1.849 times (p = 0.239) and in 2.439 times (p = 0.075) was found
      in the carriers with a complete absence of the product of genes GSTP1*B and
      NAT2*6 590G>A, correspondingly (pp genotype). A statistically significant
      decrease in OR of lung cancer was found in the wp genotype carriers of gene
      GSTP1*B (OR = 0.50, p = 0.041). Three variants of paired combinations of gene
      alleles were established in the carriers with a statistically significant
      increase in OR of lung cancer (ww GSTP1*B + pp GSTM1*0; ww GSTP1*B + pp NAT2*6
      590G>A; pp GSTP1*B + pp NAT2*5 481C>T), and one combination in the carriers with
      a statistically significant decrease in OR of lung cancer (wp GSTP1*B and ww +wp
      GSTT1*0).

PMID- 25775824
TI  - [On the issue of non-mutagenic non-targeted effects in low renewable tissues.
      Analysis of low dose radiation effects on the rat renal tubule epithelium].
AB  - Irradiation of rats with gamma-quanta at relatively low doses induces a
      sustainable dose-independent increase in the occurrence of lethal cytoplasmic
      disorders in the renal tubules epithelium together with sustainable and as well
      dose-independent subcelluar compensation and restorative processes. Over the
      period of research (6 months) these processes led to no population recovery. The
      detected alterations are referred to the category of non-targeted non-mutagenic
      effects and they are of interest because they address the issue of the
      sensitivity of low renewable tissues to radiation.

PMID- 25775825
TI  - [Photosensitizing properties of 3,3'-diethylthiacarbocyanine in biological
      media].
AB  - The objective of the study is elucidation of perspectives of 3,3'
      diathylcarbocyaine application as a photosensitizer for curing viral infections
      by photodynamic therapy. Lipid-containing bacteriophage PM-2 of Pseudoalteromonas
      espejiana was used as a model. The testing was carried out at a special
      installation modeling photodynamic exposure conditions towards a non-fractionated
      phage lysate. 3,3'-DECC demonstrated a rapid photo-bleaching when added tothe
      phage lysate but not to water. The initial rate of PM-2 phage photoinactivation
      was proportional to the square concentration of the dye in the range of 0.5-9
      MUmol/L. This confirms a hypothesis that the dimer is the principal
      photochemically active form of the dye. An improved ability to form dimers was
      found in the dye in the phage lysate (10-folds better than in the water). The dye
      formed a stable adduct with the bacteriophage material. This adduct had an
      extinction maximum at lambda(max) = 594 nm and demonstrated the properties of a
      polymer (sedimentation under a low-speed centrifugation).

PMID- 25775826
TI  - [The influence of uranyl in nanomolar concentrations on erythrocyte sensitivity
      (in vitro) to factors inducing acute oxidative stress].
AB  - The influence of nanomolar concentrations of UO2Cl2 on the erythrocyte
      sensitivity (in vitro) to the factors inducing acute oxidative stress was
      investigated. It was shown that even a short-run exposure of uranyl ions resulted
      in the changes of the physico-chemical properties of the membrane. It can
      affectnot only the survival of cells but significantly modify their reaction on
      the effect of damaging factors, particularly on the impact of oxidative stress
      inductors. The character of modification depends on a radical source and results
      from the mechanisms of their effects on the cell and the ability of uranyl to
      catalyze ROS-forming processes. The detailed investigation into the mechanisms of
      the effect of uranyl ions at low concentration on cells is required.

PMID- 25775827
TI  - [Damage and functional recovery of the mouse retina after exposure to ionizing
      radiation and methylnitrosourea].
AB  - The eye retina consists of terminally differentiated cells that have lost their
      ability to proliferate. The death of these cells leads tothe loss of sight. The
      mice retina is characterized by relatively high resistance to radiation, which is
      provided by its ability to repair damage caused by environmental factors. The aim
      of our work was to assess the damaging effect of ionizing radiation and
      methylnitrosourea (MNU) on the DNA structure in the mouse retina, the functional
      activity of the retina, and its ability to recover in vivo. The results confirm
      the ability of the mature retina to structural and functional recovery. Adapting
      influence of low dose chemical agent increases retina resistance to cytotoxic
      dose of genotoxicants and prevents degeneration of photoreceptor layer of the
      retina. The results show the possibility of neurohormesis effect in the mice
      retina after exposure to ionizing radiation and chemicals.

PMID- 25775828
TI  - [Pulse flows of populations of cortical neurons under low-intensity pulsed
      microwave: interspike intervals].
AB  - Pulse flows of populations of cortical neurons were investigated on
      unanesthetized nonimmobilized rabbits prior, during, and after 1-min microwave
      irradiation (wavelength 37.5 cm, power density 0.5-1.0 mW/cm2) in continuous and
      pulse-modulated modes with a frequency of 5, 20 and 100 Hz. The changes in the
      characteristics of interspike intervals resulted from these exposures. The
      peculiarity of rearrangements of pulse flows and their dynamics was determined by
      modes of irradiation.

PMID- 25775829
TI  - [Accumulation of radionuclides in food chains of the Yenisei River after the
      nuclear power plant shutdown at the mining-and-chemical enterprise].
AB  - Accumulation of artificial and natural radionuclides in the chains of food webs
      leading to non-predatory and piscivorous fish of the Yenisei River was
      investigated during one year before and three years after the shutdown of a
      nuclear power plant at the Mining-and-Chemical Combine (2009-2012). The activity
      of artificial radionuclides in the samples of biota ofthe Yenisei River (aquatic
      moss, gammarids, dace, grayling, pike) was estimated. The concentration of
      radionuclides with induced activity (51Cr, 54Mn, 58Co, 60Co, 65Zn, 141, 144Ce,
      152, 154Eu, 239Np) decreased in the biomass of biota after the shutdown of the
      nuclear power plant; the concentration of 137Cs did not. Analysis of the
      accumulation factors (C(F)) allows us to expect the effective accumulation of
      137Cs in the terminal level of the food web of the Yenisei River--pike (C(F) =
      2.0-9.4), i.e. biomagnifications of radiocesium. Accumulation of artificial,
      radionuclides in non-predatory fish from gammarids was not effective (C(F) < 1).
      An effective accumulation of 40K is possible in muscles of non-predatory and
      piscivorous fish species from food (C(F) = 2:6-3.1 and 1.3-1.4, respectively).
      C(Fs) of K and 40K were equal in all trophic pairs, but C(Fs) of 40K and 137Cs
      differed considerably.

PMID- 25775830
TI  - [Prospects of systemic radioecology in solving innovative tasks of nuclear power
      engineering].
AB  - A need of systemic radioecological studies in the strategy developed by the
      atomic industry in Russia in the XXI century has been justified. The priorities
      in the radioecology of nuclear power engineering of natural safety associated
      with the development of the radiation-migration equivalence concept, comparative
      evaluation of innovative nuclear technologies and forecasting methods of various
      emergencies have been identified. Also described is an algorithm for the
      integrated solution of these tasks that includes elaboration of methodological
      approaches, methods and software allowing dose burdens to humans and biota to be
      estimated. The rationale of using radioecological risks for the analysis of
      uncertainties in the environmental contamination impacts,at different stages of
      the existing and innovative nuclear fuel cycles is shown.

PMID- 25775831
TI  - [On the problem of biodiagnostics under conditions of radioactive contamination].
AB  - The possibilities of biodiagnostics methods (bioindication and bioassay) have
      been analyzed for conditions of radioactive contamination of natural ecosystems
      components. The prospects of using biodiagnostics data to address some practical
      radioecology problems are discussed. The data on dynamics of long-term indicators
      in the ecosystems contaminated after the Chernobyl accident are shown. The
      authors have formulated a number of provisions relating to the accumulative
      bioindication for structural components of forest ecosystems (arboreal and
      herbaceous vegetation, mosses, lichens, higher fungi).

PMID- 25775832
TI  - [V.I.Vernadskii's theory of the biosphere and modern problems of radioecology].
AB  - The importance of Vernadsky's scientific heritage for the present stage of
      science development was substantiated. His role in the formation of radioecology
      as an independent scientific discipline was emphasized. The ecological
      consequences of an anthropogenic increase of the radiation background and the
      prospects of nuclear energy development were considered.

PMID- 25775833
TI  - ["Biological effects of low doses of ionizing radiation and radioactive
      contamination of the environment" (BIORAD-2014)].

PMID- 25775834
TI  - [Dmitrii Mikhailovich Grodzinskii celebrates the 85th anniversary].

PMID- 25775835
TI  - [Nikolai Petrovich Lysenko celebrates the 60th anniversary].

PMID- 25775836
TI  - [Personalized treatment of tumor-bearings after prediction of radio and
      chemoradio-therapy efficacy by means of blood DNA radiosensitivity].
AB  - Ongoing studies on the tumor and non-tumor samples carried out worldwide give
      evidence that some apoptotic indexes, DNA-based microarray molecular profiling
      analysis as well as determination of single nucleotide polymorphisms in the
      genome of a patient's tumor can serve perspective markers of radiosensitivity for
      the response prediction in individual patients to intendedradiation therapy. Over
      the last years there has been an increasing interest in radiogenomic and
      characterization of DNA array molecular profiles that can predict the response to
      irradiation in tumor and non-tumor tissues. Now a technology of the short-term
      and inexpensive determination of indices aimed at an objectively based use of
      radiation therapy in experiment or clinic after evaluation of blood DNA
      radiosensitivity has been developed.

PMID- 25775837
TI  - [Repeated computed tomography examinations: radiation dose and radiation risk in
      malignant lymphomas].
AB  - The aim of the study was to determine the number, types and time periods of
      computed tomography (CT) examinations in the patients with lymphomas, to estimate
      the obtained radiation doses and the attributable risk of cancer. 50 patients
      aged 18-83 years, 25 men and 25 women who received treatment in 2010-2011 were
      included in a retrospective study. There were 19 patients with Hodgkin Disease
      and 31 patients with Non-Hodgkin's Lymphoma. During the monitoring period there
      665 CT examinations were conducted including 169 (25%) prior to treatment, 244
      (37%) during chemotherapy, 54 (8%) for radiation therapy planning and 198 (30%)
      after end of treatment. The average number of CT examinations per patient was
      13.3 (range 3-29). 32 (64%) patients underwent 10 and more CTs, 10 (20%) patients
      -20 and more. The most commonly performed examination was CT of the chest. Number
      of CT controls after treatment per patient averaged 2.7 (range 1-6). The mean
      effective dose per patient was 86.7 mSv (range 21.7-209.2 mSv). 37 (74%) patients
      received more than 50 mSv during the entire period, 14 (28%) patients--more than
      100 mSv, 6(12%) patients--more than 150 mSv and 1 (2%) patient--more than 200
      mSv.6 (12%) patients received more than 100 mSv during one year. The collective
      radiation dose was 4.3 Sv. In 50 patients, we can expect 0.176 additional cases
      of cancer which is equivalent to the risk of 0.35% or 1 case per 256 patients.

PMID- 25775838
TI  - [Radiation-induced reactions in breast cancer patients after breast-conserving
      surgery with intraoperative and external beam radiotherapy].
AB  - The present study is aimed to evaluate the frequency and severity of radiation
      induced reactions in patients with stage T1-2N0-1M0 breast cancer, who received
      intraopeartive radiation therapy (IORT) in combination with external beam
      radiotherapy (EBRT). A small-size betatron producing 6 MeV electron beam was used
      for IORT. External beam radiotherapy was performed using Rokus and Theratron
      machines. Radiotherapy treatment was planned using a specially devised method to
      ensure acceptable levels of severity and frequency of radiation reactions. The
      patients were divided into 3 groups: the study (40 patients), control (88) and
      comparison (50) ones. Radiation-induced skin reactions in the study group ranged
      from erythema to moist desquamation and edema. Magnetic laser therapy was used to
      treat radiation-induced injuries. The applied method of estimating the total dose
      of IORT and EBRT was shown to provide the acceptable levels of severity and
      frequency of radiation reactions.

PMID- 25775839
TI  - [Increase of X-ray radiotherapy antineoplastic efficacy by use of a gadolinium
      containing pharmaceutical].
AB  - The influence of the gadolinium-containing drug Dipentast (0.5 M water solution
      of sodium gadopentetate) on the antineoplastic efficacy of X-ray radiotherapy has
      been studied. Dipentast possesses neither intrinsic antitumor effect, nor tumor
      seeking capability. Mice C57Bl/6 with transplanted adenocarcinoma Ca755 were used
      in the study. The mice were irradiated with an X-ray machine with an anode
      voltage of 200 kV. The absorbed dose in the tumor after irradiation was 10 Gy for
      both experimental and control groups. The mice in the experimental group were
      treated with a single intraperitoneal injection of 0.3 ml of Dipentast. The
      observation of the tumour growth rate has shown that intraperitoneal
      administration of Dipentast prior to X-ray irradiation results in a significant
      tumour growth delay (12 +/- 1 days for the experimental group versus 2 +/- 1 in
      the control group), increasing the median life span from 36 +/- 1 days in the
      control group to 43 +/- 1 days in the experimental group, and leads to complete
      disappearance of the tumour in 25 +/- 1% of the animals in the experimental
      group, while in the control group, no tumour regression was observed.

PMID- 25775840
TI  - [Role of DNA repair genes in radiation-induced changes of lifespan of Drosophila
      melanogaster].
AB  - One of the main effects of various stress factors, including ionizing radiation,
      is DNA damage. Accumulation of DNA damage and somatic mutations in the somatic
      tissues is regarded as one of the basic mechanisms of aging. We have developed an
      approach to the study of molecular and genetic mechanisms of radioadaptation,
      which is based on the analysis of changes in the lifespan of Drosophila with a
      transformed genotype. In this study we investigated the radioadaptive response
      and hormesis by radiation-induced changed of the lifespan of different strains of
      Drosophila melanogaster, such as a wild type strain Canton-Sand strains with
      mutations in DNA damage response gene (homologue of GADD45), excision repair
      genes (homologues of XPF, XPC, PCNA) and double-strand breaks repair genes
      (homologues of RAD54, XRCC3, BLM). The exposure to irradiation at the dose rate
      of 40 cGy was performed chronically through the stages of fly development; an
      acute exposure at the dose rate of 30 Gy was applied to the adult stages of
      flies. Also, we investigated the resistance to acute gamma-radiation of
      Drosophila with conditional ubiquitous overexpression of genes that are involved
      in DNA damage recognition (homologues of GADD45, HUS1, CHK2), excision repair
      (homologues of XPF, XPC, AP-endonuclease-1) and double-strand break repair
      (homologues of BRCA2, XRCC3, KU80, WRNexo). In the wild type strain Canton-S,
      manifestation of the radioadaptive response and radiation hormesis were observed.
      In individuals with DNA repair gene mutations, no radioadaptive response was
      observed, or observed to a lesser extent than in wild type flies. Mifepristone-
      inducible transgene activation does not lead to an increase in resistance to
      acute irradiation by the parameters of lifespan of Drosophila. Overexpression of
      DNA repair genes led to a sharp decline in lifespan also in the absence of
      irradiation.

PMID- 25775841
TI  - [Study of the influence of low-dose gamma-irradiation on the functional state of
      peripheral blood erythrocytes of rats].
AB  - Low-intensity radiation at the absorbed dose of 4 MUGy/min is a stressor of
      medium strength. In male Wistar rats, a pronounced and long-lasting response
      occurs in the system of red blood cells at the accumulated dose of 4.8 mGy.
      Functional deficiency of circulating cells was evaluated by the resistance of
      erythrocytes to acid lyse and the activity of the main antioxidant enzymes-
      superoxide dismutase (SOD) and catalase (CAT). The minimum "threshold" doses of
      radiation that cause systemic reactions occur in the range of units of miligrey.

PMID- 25775842
TI  - [On the mechanism of radioprotective effect of NO-synthase inhibitors].
AB  - We studied the influence on hemodynamics and radioprotective activity of two
      inhibitors of NO-synthase (NOS)--isothiourea derivatives with different NOS
      isoform selectivity: T1023--a selective inhibitor of endothelial and inducible
      NOS; and NTT2--a highly selective inhibitor of neuronal NOS. Both compounds at a
      dose of 1/7 LD50/15 caused a vasopressive effect and baroreflex response in
      normal Wistar rats. However, the nature of hemodynamic changes was qualitatively
      different. T1023 caused a prolonged elevation of vascular tone and reflex shift
      resulted in a significant and lasting reduction in the systemic blood flow (35
      45%), which created conditions for the development of circulatory hypoxia. The
      use of NTT2 caused a reflex change in hemodynamics accompanied by vasodilation;
      and systemic blood flow was maintained at the initial level. T1023 effectively
      protected mice subjected to 10 Gy gamma-irradiation and their bone marrow stem
      cells irradiated with 6 Gy, not yielding to the radioprotective effect of
      cystamine. NTT2 at these doses did not show any radioprotective effect. The
      obtained results support the leading mechanism of the radioprotective effect of
      NOS inhibitors is the induction of hypoxia. With this mechanism of action a
      significant radioprotective activity can be expected for the inhibitors which
      effectively suppress primarily endothelial NOS.

PMID- 25775843
TI  - [Birth defects on Chernobyl radionuclide polluted territories].
AB  - 147318 pregnancy outcomes were analyzed in Zhytomyrska Oblast during 2000-2010;
      the descriptive analysis was performed. The frequency of birth defects was
      estimated among newborns, still-born babies and abortions due to genetic
      disorders of a fetus on "clean" and polluted territories. There was an increase
      of all birth defects on the polluted territories; among newborns it was (26.10 +/
      0.80) per thousand and (24.23 +/- 0.47) per thousand, p < 0.05; among newborns
      and still-born babies it was (26.54 +/- 0.81) per thousand and (24.78 +/- 0.48)
      per thousand, p < 0.06. The increase in the birth defects of the nervous system
      was detected: among newborns it was (1.09 +/- 0.17) per thousand and (0.75 +/-
      0.08) per thousand, p < 0.05; among newborns and still-born babies it was (1.22
      +/- 0.18) per thousand and (0.81 +/- 0.09) per thousand, p. < 0.05; among
      newborns, still-born babies and genetically caused abortions it was 2.76 +/-
      0.26) per thousand and (2.34 ? 0.15) per thousand, p = 0.165. Chi2 criteria
      confirmed the difference between the frequency of birth defects on "clean" and
      polluted territories. Estimation by Bayes did not confirm the hypothesis about
      the difference between the frequency of birth defects on "clean" and polluted
      territories. Endocrine diseases were confirmed to be an important factor of the
      origin of birth defects, which is important for planning pregnancy on both
      polluted and "clean" territories.

PMID- 25775844
TI  - [Effect of low-intensity 900 MHz frequency electromagnetic radiation on rat liver
      and blood serum enzyme activities].
AB  - The comparative analysis of the rat liver and blood serum creatine kinase,
      alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase and
      purine nucleoside phosphorylase post-radiation activity levels after a total two
      hour long single and fractional exposure of the animals to low-intensity 900 MHz
      frequency electromagnetic field showed that the most sensitive enzymes to the
      both schedules of radiation are the liver creatine kinase, as well as the blood
      serum creatine kinase and alkaline phosphatase. According to the comparative
      analysis of the dynamics of changes in the activity level of the liver and blood
      serum creatine kinase, alanine aminotransferase, aspartate aminotransferase and
      purine nucleoside phosphorylase, both single and fractional radiation schedules
      do not affect the permeability of a hepatocyte cell membrane, but rather cause
      changes in their energetic metabolism. The correlation analysis of the post
      radiation activity level changes of the investigated enzymes did not reveal a
      clear relationship between them. The dynamics of post-radiation changes in the
      activity of investigated enzyme levels following a single and short-term
      fractional schedules of radiation did not differ essentially.

PMID- 25775845
TI  - [Induction of native platelets aggregation by incubation media of the UV
      irradiated leukocytes: possible role of the photo-induced ADP release].
AB  - It is shown that during incubation after UV irradiation (22-24 hours at 7-9
      degrees C) irradiated isolated rabbit leukocytes release the compound(s) which
      induces platelets aggregation in the native platelet rich plasma. Treatment of
      the incubation media of irradiated leukocytes by heat (5 minutes at 100 degrees
      C) does not significantly change its pro-aggregation activity. Treatment of the
      platelet-rich plasma by the incubation media of irradiated leukocytes without
      stirring induces the refractoriness of platelets to ADP. The platelets treated by
      ADP without stirring do not react to the incubation media of irradiated
      leukocytes. The absorption spectrum of the incubation media of irradiated
      leukocytes has the maximum at 260 nm similar to that of the absorption spectra of
      ADP. It is possible that UVradiation induces the ADP release from leukocytes
      during post-irradiation incubation. Accumulation of this substance in the
      incubation media may be the cause of its pro-aggregation activity for native
      blood platelets.

PMID- 25775846
TI  - [Spatial variability of quasidiffusion coefficients for 137Cs in grey forest
      soils in the distant zone of contamination from the Chernobyl NPP].
AB  - The calculated values of quasidiffusion coefficients for 137Cs for the 15-year
      period after the Chernobyl fallout in the top mineral thickness of grey forest
      soils of the Tula region vary within 0.18-0.35 cm2/year, accruing among
      biogeocenoses: pine forest < oak forest < birch forest < pasture. Correlations
      are revealed and the equations of linear regression for quasidiffusion
      coefficients for 137Cs depending on soil properties are constructed. Estimates of
      the periods of effective residence half-time of 137Cs in grey forest soils are
      made: for a layer of 0-5 cm - 11-14 years 0-15 cm - 22-25 years, 0-30 cm - 27-28
      years. The periods necessary for the decrease in the contents of 137Cs in a 0-5
      cm layer of soils to the level of 37 kBq/m2 are considered, taking into account a
      spatial variation of fallout and heterogeneity of quasidiffusion. Forecasts of
      the vertical migration of 137Cs on the basis of the diffusive model with
      spatially distributed soil parameters are submitted.

PMID- 25775847
TI  - [Radiological control of silvicultural production in Perm Krai].
AB  - Results of the studies carried out in 2009-2012 on the 137Cs content in edible
      fungi, berries and fruits of wild-growing bushes and the low shrubs growing in
      forest ecosystems of a number of regions of the Perm Krai are presented. It is
      shown that the activity of radio caesium in the studied samples does not exceed
      the maximal allowed levels approved in the Russian Federation.

PMID- 25775848
TI  - [XIV International Youth Scientific School named after A.S. Saenko "Modern
      problems of radiobiology"].

PMID- 25775849
TI  - [On the anniversary of Elena Borisovna Burlakova].

PMID- 25775850
TI  - [Multinuclear blue copper-proteins: the evolutionary design].
AB  - The review presents both our and literature data of results of studies of
      pathways of evolution of the so-called multinuclear blue copper-proteins (MBCP)
      that have the domain organization. The MBCP are widely spread in living nature,
      they have been revealed in cells of archais, bacteria, and eukaryotes. Included
      in the MBCP composition are such different by their functions copper-proteins as
      oxidases, reductase, blood coagulation factors V and VIII. Most likely, MBCP have
      been originated from the low-molecular protein-precursor similar topologically
      with blue electron-transporting protein of the type of cupredoxin, as a result of
      action of various evolutionary mechanisms: amplification of genes, formation of
      protein structures by different combinations of domains, a change of size of
      domains, the segment elongation at the expense of the activational domain,
      formation and loss of various copper-binding centres, variation of amino acid
      ligands in such centres, the appearance of centres of binding of other proteins,
      glycosylation, etc.

PMID- 25775851
TI  - [Functional states of the antioxidant enzymatic complex of tissues of Mytilus
      galloprovincialis Lam. under conditions of oxidative stress].
AB  - There are generalized materials on reaction of enzymatic antioxidant (AO) complex
      of tissues of molluscs of the genus Mytilus to oxidative loading of different
      intensity. It is shown that with increase of level of oxidative stress, a rise of
      activity of glutathione peroxidase (GP) and glutathione reductase (GR) is
      observed, as well as the rate of glutathione (GSH) in tissues also increases.
      Then the toxic loading is compensated by a rise of activities of enzymes of low
      affinity to hydroperoxides, specifically of catalase. In the glutathione system,
      it is possible to identify several relatively steady states: of low, moderate,
      and highly intensive processes. In several tissues, functioning of the AO system
      seems to be directed not to rendering harmless, but to generation of reactive
      oxygen species (O2-, superoxide dismutase), which is likely to be determined by
      specificity of their running processes (destruction of damaged byssus theads).
      The molluscan AO complex is characterized by high lability and sensitivity both
      to physiological states (spawning) and to action of factors of anthropogenic
      nature (cationic detergents). Reactions of AO complex of the mussel to the
      natural states and to toxic action are comparable between each other, which is
      necessary to be taken into account at diagnostics of the aquatic medium.

PMID- 25775852
TI  - [Character of changes of the level of serotonin-modulating anticonsolidation
      protein and of cytochrome P-450 in tissues of the eastern alburnoid Alburnoides
      bipunctatus eichwaldi from rivers of Azerbaijan].
AB  - The paper deals with study by the method of solid-phase indirect immunoenzyme
      analysis of levels of the novel serotonin-modulated anticonsolidation protein
      (SMAP) that is directly correlated with serotonin level as well as of biomarker
      cytochrome P-450 in the liver, gills, and brain of the eastern alburnoid
      (Alburnoides bipunctatus eichwaldi) caught in the rivers Khudat, Akstafachai,
      Kura, and Araks flowing at the territory of Azerbaijan. There was revealed a
      marked downregulation of cytochrome P-450 and SMAP in the liver and gills of the
      fish caught in the Akstafachai River relatively to values in the fish from the
      Khudat River not contaminated with pollutants. In the liver and gills in the fish
      from the Kura and Araks rivers, a significant differently directed changes of the
      cytochrome P-450 and SMAP levels were observed: downregulations of the cytochrome
      P-450 versus an upregulation of SMAP. In the brain of the fish from the River
      Akstafachai there was observed some downregulation of cytochrome P-450, whereas
      in fish from the Kura and Araks rivers--a significant upregulation of the SMAP
      level. The obtained results are analyzed from standpoint of processes of
      adaptation and disadaptation of aquatic organisms to impact of pollutants.

PMID- 25775853
TI  - [Action of yttrium on calcium-dependent processes in myocardium of vertebrates].
AB  - This work deals with study, of effect of yttrium acetate (Y3+) on myocardium of
      the frog Rana redibunda and of its action on the ion transport across the inner
      membrane of the rat heart mitochondria. It was found that Y3+ decreased strength
      of heart contractions and facilitated transport of ions in rat heart mitochondria
      stimulated by 10 mM glutamate and 2 mM malate. In the presence of Y3+, the energy
      dependent transport of Ca2+ in mitochondria was inhibited; this was manifested as
      a decrease of their swelling in the medium containing 125 mM NH4NO3 and Ca2+ or
      25 mM potassium acetate, 100 mM sucrose and Ca2+. It is assumed that the Y(3+)
      caused decrease of the heart muscle contractility is not only due to its direct
      blocking effect on the potential-operated Ca2+ channels of the pacemaker and
      contractile cardiomyocytes, but also due to its mediated action on active
      transport of Ca2+ in mitochondria. The data that Y3+ activates transport of K+
      via the mitochondrial potassium uniporter and blocks Ca(2+)-channels of the inner
      mitochondrial membrane are important for better understanding of mechanisms of
      action Y3+ on cardiomyocytes of vertebrate animals and humans and the possible
      use of Y3+ in medicine.

PMID- 25775854
TI  - [Social domination and reproductive success in male laboratory mice (Mus
      musculus)].
AB  - The goal of the present study was to evaluate effect of social status and
      genotype on success of reproduction of male laboratory mice with use of
      ethological model of social hierarchy of "minimal socium". The model represents
      the paired maintenance of two male mice of different genotype (PT and CBA/Lac).
      The mice lived for 30 days in one experimental cage males, two females of the
      DD/He strain were supplemented. Regardless of genotype, the dominants became
      fathers more often than the subordinants and got more progeny. It was established
      that in subordinates there did not occur the complete suppression of fertility.
      This is suggested to allow them to realize the genetical contribution to the next
      generation and to remain in the gene pool of population.

PMID- 25775855
TI  - [Change of character of intersystemic interactions in newborn rat pups under
      conditions of a decrease of central influences (urethane anesthesia)].
AB  - On newborn rat pups, for the first day after birth, there was studied the
      character of mutual influences between the slow-wave rhythmical components of the
      cardiac, respiratory, and motor activities reflecting interactions between the
      main functional systems of the developing organism. The study was carried out in
      norm and after pharmacological depression of the spontaneous periodical motor
      activity (SPMA) performed by narcotization of rat pups with urethane at low (0.5
      g/kg, i/p) and maximal (1 g/kg, i/p) doses. Based on the complex of our obtained
      data, it is possible to conclude that after birth in rat pups the intersystemic
      interactions are realized mainly by the slow-wave oscillations of the near- and
      manyminute diapason. The correlational interactions mediated by rhythms of the
      decasecond diapason do not play essential role in integrative processes.
      Injection to the animals of urethane producing selective suppression of reaction
      of consciousness, but not affecting activating influences of reticular formation
      on cerebral cortex does not cause marked changes of autonomous parameters, but
      modulates structure and expression of spontaneous periodical motor activity.
      There occurs an essential decrease of mutual influences between motor and
      cardiovascular systems. In the case of preservation of motor activity bursts, a
      tendency for enhancement of correlational relations between the modulating
      rhythms of motor and somatomotor systems is observed. The cardiorespiratory
      interactions, more pronounced in intact rat pups in the near- and many-minute
      modulation diapason, under conditions of urethane, somewhat decrease, whereas the
      rhythmical components of the decasecond diapason--are weakly enhanced.

PMID- 25775856
TI  - [Metabotropic receptor of the group I of the 5th subtype (ImGLuR5) in honeybee
      associative olfactory learning].
AB  - The work deals with study of character of localization in the honeybee head
      ganglion of metabotropic receptor ImGluR5 and its role in memory formation. With
      aid of pharmacological method (injections of antisense oligonucleotide and of
      selective receptor agonist and antagonist) and of behavioral criterion (formation
      and testing of preservation in memory of conditioned alimentary reflex for
      olfactory stimulus), there is first shown participation of the studied receptor
      in formation of the honeybee long-term memory. By using the immunohistochemical
      method, there is first revealed the predominant expression of the ImGluR5
      receptor in the mushroom body Canyon cells responsible for the insect integrative
      activity. The present study, together with the previous ones, allows concluding
      about the presence in the honeybee head ganglion of the group I of metabotropic
      glutamate receptors with two subtypes 1 and 5 (ImGluR1,5) that have similar with
      mammalian pharmacological properties favoring preservation of the individually
      acquired experience in the long-term memory.

PMID- 25775857
TI  - [Seasonal fluctuations of migratory activity of vertebrate nuclear hemocytes at
      different incubation temperatures].
AB  - Agarose migration test has shown that nuclear erythrocytes of Cyprinus carpio,
      Rana ridibunda, and Gallus domesticus are capable for spontaneous locomotions.
      The migration of red blood cells from frogs is associated with formations of long
      pseudopodia, whereas that from carps and hens--with short protrusions. It has
      been shown that migratory activity of nuclear erythrocytes and leukocytes from
      Rana ridibunda and Gallus domesticus under effect of temperature in vitro had
      seasonal nature, while that from Cyprinus carpio did not depend on the year
      season. In frogs and hens the circadian oscillations of blood cell migration area
      are coupled with the organism functional activity, whereas no such associations
      is present in carps.

PMID- 25775858
TI  - [The main statements of a new concept about the substrate of paleoamygdala].
AB  - A new concept is presented about the substrate of paleoamygdala--a complex of the
      gray matter located in the periventricular zone of the lower horn of the lateral
      ventricle at the territory of the posterior part of the phylogenetically ancient
      cortical-medial grouping of the amygdalar complex. The argumentation is based on
      results of cytoarchitectonical analysis, consideration of peculiarities of
      neuronal organization, regularities of ontogenesis, and the literature data
      characterizing results of hodological and functional investigations.

PMID- 25775859
TI  - [Natalia Fiodorovna Avrova (the 75th anniversary from the birthday)].

PMID- 25775860
TI  - [A current viewpoint on structure and evolution of collagens. II. The fibril
      associated collagens with interrupted triple helices].
AB  - Fibril-associated collagens with interrupted triple helices (FACITs) form one of
      the subfamilies of collagen family. Being minor components of connective tissues
      in multicellular animals, FACITs play an important role in structurization of
      extracellular matrix whose peculiarities determine differences among tissues.
      FACITs take part in regulation of the sizes of banded collagen fibrils and are
      also a link between diverse components of extracellular matrix and cells in
      different tissues. The functional characteristics of FACIT molecules are
      determined by peculiarities of alpha-chain structure (interruptions in
      collagenous domains and module structure of N-terminal noncollagenous regions),
      trimeric molecules (trimerization domains), and supramolecular assemblies
      (mainly, association with banded fibrils and inability to form homopolymeric
      suprastructural aggregates). The evolution of FACITs is also discussed. A
      hypothetical model of structural changes leading to formation of FACIT subfamily
      is propounded.

PMID- 25775861
TI  - [The functional role of membrane-bound adenylyl cyclases and the receptors and G
      proteins coupled with them in regulation of spermatozoa fertility].
AB  - The cAMP-dependent signaling pathways play a crucial role in regulation of
      spermatozoa fertility. The cAMP synthesis in spermatozoa is carried out both by
      soluble and by transmembrane (membrane-bound) forms of adenylyl cyclase (AC). For
      the last years, numerous data have been appeared on the presence of a wide
      variety of membrane-bound AC isoforms in spermatozoa at different stages of their
      maturation and the regulation of the enzymes by hormones and hormone-like
      substances through G protein-coupled receptors (GPCR). In spermatozoa,
      functioning as GPCR agonists may be adenosine, biogenic amines, peptide hormones,
      and odorants. The study of structural-functional organization and regulatory
      properties of the AC signaling system in spermatozoa is of great practical
      importance for reproductive technology, as the membrane-bound AC forms and the
      signaling cascades coupled with them are involved in controlling processes, such
      as chemotaxis and motility of spermatozoa, their capability for capacitation and
      acrosomal reaction. In this review the data on the functioning and the role of AC
      signaling system in spermatozoa of human and vertebrates are summarizes and
      analyzed, and the achievements and unresolved problems in this area are
      discussed.

PMID- 25775862
TI  - [Fatty acid composition of phospholipids of erythrocytes of lamprey, frog, rat,
      and absorption spectra of their lipid extracts].
AB  - The work deals with study of content and fatty acid composition of phospholipids
      as well as of absorption spectra of lipid extracts of blood erythrocytes
      poikilothermal and homoiothermal animals of different evolutionary levels.
      Objects of study were poikilothermal lamprey (Lampetra fluviatilis) consuming
      oxygen from water and the common frog (Rana temporatia) consuming it both from
      water and from air. Homoiothermal animals were white rats (Rattus rattus)
      inhabiting in the air medium. The animals were studied at the winter-spring
      periods. There was established the twofold predominance of the phospholipid
      content in the lamprey plasma as compared with erythrocytes. In frog and rat the
      reverse ratio was observed. Based on study of the fatty acid composition of
      erythrocyte phospholipids it is suggested the higher density of membranes of
      lamprey as compared with frog membranes. As to fatty acides of the rat blood
      erythrocytic fraction, they turned out to be less diverse, with almost twofold
      predominance of saturated over unsaturated acids and not containing the long
      chained (C22) Omega3 acids. All this leads to the low unsaturation index and,
      accordingly, to a dense packing of fatty acids in membrane structures of rat
      erythrocytes. Mechanism of reversible binding of O2 molecules by hemoglobin in
      erythrocytes is discussed. The mechanism of interaction of O2 molecules with
      water molecules is likely to interfere with exchange interaction electrons of
      hemoglobin iron atoms and oxygen molecule. This confirms our obtained absorption
      spectra showing that in the lipid extract practically not containing water the
      heme isolated from erythrocytes is converted to hemin.

PMID- 25775863
TI  - [The functional activity of thyroid of male rats with acute and mild
      streptozotocin diabetes].
AB  - The type 1 diabetes mellitus (DM1) and dysfunction of thyroid are the most common
      endocrine diseases, which are interrelated. However, the molecular mechanisms of
      thyroid dysfunction in DM1 and the role of adenylyl cyclase signaling system
      (ACSS) in this process remain poorly understood. Typically for studying etiology
      and pathogenesis of thyroid diseases in DM1 the models of acute DM1 induced by
      high doses of streptozotocin (STZ) are used. At the same time, a suitable model
      for this purpose is the model of mild DM1 induced by moderate doses of STZ, which
      more closely resembles human DM1. The aim of this work was a comparative study of
      the thyroid functional state in rats with 30-day acute DM1 induced by injection
      of STZ at a dose of 65 mg/kg, and in rats with the 30- and 210-day mild DM1
      induced by three consecutive injections of STZ at medium doses (30-40 mg/kg). For
      this purpose in diabetic animals the levels of thyroid hormones and TSH and the
      functional activity of hormone-sensitive ACSS in membranes isolated from thyroid
      were studied. It was shown that in blood of rats with acute DM1 the levels of
      fT4, fT3 and tT3 were decreased by 45%, 23% and 19%, respectively, while the
      level of TSH did not changed significantly. In rats with 30-day mild DM1 the
      concentration of fT4 was decreased by 32%, while the levels of tT4, tT3 and TSH
      were similar to those in control. In rats with prolonged mild DM1 after 150 and
      210 days after the first treatment with STZ the levels of tT4, fT4 and tT3 were
      significantly reduced, but the concentration of TSH in rats with 210-day mild DM1
      was increased by 119%. The results obtained in the study of the thyroid status
      and TSH levels in rats with prolonged mild DM1 are in good agreement with the
      data obtained in the study of thyroid diseases in patients with DM1. It was found
      that the basal activity of adenylyl cyclase (AC) in the membranes isolated from
      thyroid of diabetic rats did not change, except for rats with prolonged mild DM1
      where this activity was increased by 21%. In all groups of diabetic rats the
      decrease of AC stimulating effects of GppNHp (10(-5) M) and TSH (10(-8) M) was
      found, and in the rats with prolonged mild DM1 the AC effect of PACAP-38 (10(-6)
      M) was also reduced. The decrease of the AC effect of TSH varied among different
      groups of the diabetic animals: in the rats with acute DM1 this effect was
      reduced by 46% and in the rats with the 30- and 210-day mild DM1--by 18% and 34%.
      Thus, it was concluded that the key cause of thyroid resistance to TSH under
      conditions of DM1 is a weakening of the signal transduction generated by TSH via
      the ACSS.

PMID- 25775864
TI  - [Interrelation between parameters of motor activity and blood glucose
      concentration in newborn rats at starvation and under glucose load conditions].
AB  - The study is carried out the 1st-, 3rd-, 5th-, 7th, and 10th-day old free moving
      or loosely fixed rat pups (P1-10). In satiated and submitted to the 24-h
      starvation rat pups, parameters of spontaneous periodical motor activity (SPMA)
      and the blood glucose content were studied. The total glucose level in hungry rat
      pups was, on average, 1.5-2.5 times lower than in satiated animals.
      Administration of glucose to hungry rat pups increased 6-11 times its
      concentration in blood as compared with the animals not obtaining glucose. The
      glucose administration to the satiated rat pups led to a rise of its level in
      blood from 2 to 5 times as compared with intact animals, which was 2-3 times less
      than in the case of hungry animals. Analysis of pattern of motor activity
      recorded under conditions of the glucose deficit caused by the 24-h starvation of
      rat pups did not reveal significant changes of ratio of rhythmical components.
      Introduction of glucose to hungry and to the lesser degree to satiated rat pups
      led to potentiation of the minute rhythm of activity in all age groups. An
      exception was the first day after birth when the glucose administration to
      satiated rat pups promoted an enhancement of the decasecond rhythm and a decrease
      of the total level of motor activity. Comparison of ontogenetic dynamics of the
      SPMA parameters and the glucose content in blood of hungry rat pups revealed the
      clearly expressed regularity absent in the satiated animals: the glucose level in
      blood was higher during activity than in the state of rest. The performed study
      has shown that intensity, duration, and, to a degree, pattern of SPMA in the
      newborn rat pups depend on the level of satiety, and can be significantly changed
      in the artificially produced hypo- or hyperglycemia. The existing ontogenetic
      fluctuations in the character of reaction at performance of the glucose tolerance
      test can be connected both with morphofunctional maturation of the motor system
      and with immaturity of various chains of carbohydrate metabolism.

PMID- 25775865
TI  - [Involvement of Tas1r3 receptor protein in control of the metabolism of glucose
      at different levels of glycemia in mice].
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 C57BL6J-Tas1r3(tm1Rfm) (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 to disappearance glucose administration. We have shown that in
      the Tas1r3-/- strain, in addition to 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 suggested that the T1R3 is involved in regulation of
      endogenous glucose production. These data suggest that the T1R3-mediated
      glucoreception interacts with the K(ATP)-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- 25775866
TI  - [Modification of expression of neurohormones in hypothalamus of prenatally
      stressed male rats in model of posttraumatic stress disorder].
AB  - By the method of quantitative immunohistochemistry there has been studied
      expression of corticotrophin-releasing hormone (CRH) and vasopressin in
      hypothalamic paraventricular nucleus (PVN) of prenatally stressed rats in the
      experimental model of the posttraumatic stress disorder--the paradigm "stress
      restress". The prenatal stress was modeled by immobilization of pregnant female
      rats for 1 h from the 15th to the 19th day of pregnancy. It has been shown that
      in sexually mature males--descendants of stressed mothers--a decrease in
      immunoreactivity to CRH and vasopressin is observed in the parvocellular and
      magnocellular PVN areas 10 days after the restress. In the control group males
      born by intact mothers the level of immunoreactivity to CRH was increased in both
      PVN areas, whereas with respect to vasopressin--in the magnocellular area. Only
      in the prenatally stressed males there is detected a decrease in the
      corticosterone level in the blood plasma 10 days after the restress. It is
      concluded that in the control group males themanifestation of the pathological
      state in the paradigm "stress-restress" consists in hyperactivation of the
      hypothalamic chain of regulation of the hypothalamo-pituitary-adrenocortical
      system, whereas in the prenatally stressed animals, on the contrary, there is
      observed a decrease in activity both of the central (PVN) and of the peripheral
      (adrenal cortex) chain of this hormonal axis.

PMID- 25775867
TI  - [Effects of hyperbaric oxygenation on the state of subependymal microglia of the
      rat brain].

PMID- 25775868
TI  - [Temporal characteristics of impulse activity of neurons with the V-shaped
      frequency receptive fields in the house mouse (Mus musculus) auditory midbrain].

PMID- 25775869
TI  - [Fetal therapy--evaluation of intrauterine therapy in congenital cystic
      adenomatoid malformation of the lung (CCAM)].
AB  - OBJECTIVES: The aim of the study was to evaluate the efficiency of intrauterine
      treatment of large cysts in fetal lungs using thoracoamniotic shunts. MATERIAL
      AND METHODS: Our observational retrospective study was carried out on a series of
      8 fetuses who under went thoracoamniotic shunting after sonographic statement of
      large macrocystic lesions in the lungs at the Department of Gynecology Fertility
      and Therapy of the Fetus, Polish Mother's Research Institute, between 2009-2014.
      RESULTS: Mean gestational age at shunt insertion was 26.6 (range 18-33) weeks.
      Marked mediastinal shift in the echocardiographic examination was observed in all
      of the investigated cases. Five fetuses had polyhydramion, with 4 hydropic cases.
      Out of the remaining 4 fetuses without impaired cardiac function, 3 had very
      large lesions at initial presentation and 1 had a lesion that was rapidly
      increasing in size. Shunt insertion was successful in all cases. Only one patient
      went into premature labor (at 36 weeks of gestation). Mean gestational age at
      delivery was 38.2 weeks. Cesarean section was necessary in the half of the
      patients due to obstetric complications. All newborns underwent resection of the
      lesions. Three of them were operated in the first month after birth. The rest of
      the operations were postponed. Prenatal diagnosis of congenital cystic
      adenomatoid malformations was confirmed by pathologists in all cases. CONCLUSION:
      Intrauterine therapy of macrocystic lesions in fetal lungs enables to achieve
      good perinatal outcome It needs to be considered in every case of a fetus with
      developing impaired cardiac function.

PMID- 25775870
TI  - Ultrasonography for the prediction of extension of trophoblastic infiltration
      into the tubal wall in ampullary pregnancy.
AB  - OBJECTIVE: Predictive factors of damage to the Fallopian tube may guide the
      treatment for patients with tubal pregnancy. The purpose of this study was to
      evaluate the predictive value of ultrasonographic findings in patients affected
      by ampullary pregnancy for the determination of the depth of trophoblastic
      infiltration into the tubal wall on histological examination. MATERIAL AND
      METHODS: 38 patients with ampullary pregnancy undergoing salpingectomy were
      enrolled into the study. The patients were divided into two subgroups depending
      on their transvaginal sonography (TVS) findings; either an ectopic gestational
      sac containing an embryo with cardiac activity or those with a tubal ring. The
      ampullary pregnancies were histologically classified according to the depth of
      infiltration of trophoblastic tissue into the tubal wall as follows: stage I:
      limited to mucosa; stage II: extension to the muscularis layer; stage III:
      complete infiltration of the tubal wall with or without rupture of the serosa.
      The association between findings on TVS and stage of trophoblastic invasion,
      serum beta-human chorionic gonodatropin (beta-hCG) levels was evaluated. RESULTS:
      Although there was no significant difference among two groups in terms of
      histological stage of trophoblastic infiltration (p = 0.257), patients in whom an
      embryo with cardiac activity had been identified were found to have higher
      percentage of stage II (47.8%) or stage III (8.7%) invasion. However, there was a
      significant difference in serum beta-hCG levels on the day of surgery among the
      two groups (p = 0.028). CONCLUSIONS: Ultrasonographic aspect of ampullary
      pregnancy is associated with depth of trophoblastic infiltration into the tubal
      wall and serum beta-hCG levels.

PMID- 25775871
TI  - [Long-term follow-up of children with prenatally found increased nuchal
      translucency and normal karyotype].
AB  - OBJECTIVE: The aim of the study was a long-term follow-up of children with
      prenatally found increased nuchal translucency (NT) and normal karyotype.
      MATERIAL AND METHODS: The study was conducted among 147 pregnant women who
      underwent amniocentesis due to increased fetal NT with or without other
      structural anomalies in the fetus. The final analysis concerned children with
      prenatally found increased NT and normal karyotype who were at least 2 years of
      age. A questionnaire was sent to all patients who underwent amniocentesis in
      order to assess the development of the children. RESULTS: Normal karyotype was
      found in 101 (68.7%) fetuses with increased NT Complete information on the
      outcome of pregnancy and further development of the children was submitted by 70
      patients (69.3%). An abnormal outcome of pregnancy congenital structural
      anomalies and abnormal development was found finally in 17.1% of the children. In
      case of normal result of the second-trimester fetal ultrasound scan, normal
      further development was found in 93% of the children. CONCLUSIONS: 1. Further
      development of the children with prenatally found increased NT and normal
      karyotype is usually normal. 2. The degree of NT increase and the result of the
      second-trimester fetal anatomy scan seem to play the key role in the prognosis of
      further, postnatal outcome of the fetuses with increased NT 3. Normal karyotype
      in fetuses with increased NT does not exclude the possibility of an existing
      genetic syndrome.

PMID- 25775872
TI  - The evaluation of the predictive value of TNF-alpha concentration in maternal
      serum in the prediction of neonatal and maternal infection.
AB  - INTRODUCTION: The consequences of uncomplicated PPROM are serious, and the
      presence of overt intraamniotic infection (IAI) is associated with a significant
      increase in both, the maternal and fetal morbidity and mortality rate. TNF-alpha
      is a cytokine involved in systemic inflammation and plays an important role in
      modulating the acute phase reaction. AIM: The aim of this study was to evaluate
      the predictive value of TNF-alpha levels in maternal serum within 6 hours after
      pprom and in the period of up to 12 hours after delivery in the prediction of
      neonatal and maternal infection. MATERIAL AND METHODS: The investigation was
      conducted on a group of 56 women diagnosed with PPROM between 30+0 and 36+6 weeks
      gestational age. In the period of up to 6 hrs from pprom first sample of 10 ml of
      maternal venous blood for laboratory testing was taken and the level of TNF-alpha
      was measured. A second sample of venous blood was taken within 12 hrs from
      delivery to reassess the TNF-alpha levels. All the participants were divided
      retrospectively into four groups depending on the occurrence of adverse neonatal
      and maternal outcome. Measuring the concentration of TNF-alpha in maternal serum
      was performed using the elisa method (enzyme-linked immunosorbent assay).
      RESULTS: A statistically significant difference in the second assay (up to 12
      hours after delivery) between the patients with and without signs of maternal
      infection was observed concerning the TNF-alpha serum level. The concentration of
      this cytokine in maternal serum after delivery was 1.79 and 1.36 pg/ml (p < 0.05)
      respectively whereas within 6 hours from the PPROM in those two groups it was
      comparable (1.25 vs. 7.37 pg/ml - ns). Analogous observations were made in case
      of adverse neonatal outcome, where the TNF-alpha serum level within 12 hours
      after delivery was 1.70 and 1.45 pg/ml (p < 0.05) and in the period of up to 6
      hours from pprom was 1.25 vs. 1.38 pg/ml (ns) respectively CONCLUSIONS: 1. In our
      investigation the maternal serum TNF-alpha concentration testing within 6 hours
      from PPROM between 30+0 and 36+6 weeks of gestation did not allow for the
      identification of patients who are more likely to develop signs of maternal
      infection and whose infant was at risk of neonatal infection after delivery 2. In
      case of pprom between 30+0 and 36+6 weeks of gestation maternal serum TNF-alpha
      concentration testing in the period of up to 12 hours after delivery may be a
      useful diagnostic tool for identification of patients with an increased risk of
      maternal and neonatal infection. 3. The lower the gestational age at PPROM and at
      delivery the risk of neonatal infection was greater.

PMID- 25775873
TI  - The placental transfer of erythromycin in human pregnancies with group B
      streptococcal infection.
AB  - OBJECTIVES: The aim of this study was to investigate the effectiveness of
      erythromycin in preventing fetal and intrauterine group B streptococcal (GBS)
      infections. The study evaluated the penetration of erythromycin through the
      placenta, by comparing umbilical vein and maternal serum erythromycin
      concentrations. MATERIAL AND METHODS: The study subjects were 42 pregnant women,
      with GBS-positive screening or whose laboratory screening was not available, who
      delivered between 17th April 2013 and 22nd July 2013. The women were given 600 mg
      of erythromycin intravenously. After delivery blood was drawn from the mother's
      antecubital vein and umbilical cord vein. Serum erythromycin concentrations were
      evaluated using enzyme-linked immunosorbent assay (ELISA) kit. The percentage and
      correlation between umbilical vein and maternal serum erythromycin concentration
      were calculated. Based on regression function parameters selected factors:
      maternal age, maternal body weight, gestational age at delivery related to the
      umbilical vein serum erythromycin concentration, were investigated. Results: A
      total of 42 umbilical vein-maternal serum pairs were included in the analysis.
      The mean umbilical vein-maternal serum erythromycin concentration percentage was
      2.64 +/- 1.55%. There was a moderate correlation between umbilical vein serum and
      maternal serum erythromycin concentration. Pregnancy complications and selected
      variables of mothers in control group had no effect on the serum erythromycin
      concentration in the umbilical vein. CONCLUSIONS: Intravenous application of
      erythromycin at a dose of 600 mg, allowed to achieve therapeutic concentration in
      maternal serum. However, when it comes to placental transfer of erythromycin, the
      lack of therapeutic concentration in umbilical vein serum was observed. The
      limited transplacental transfer of erythromycin, which was approximately 2.6%,
      suggests compromised efficacy in the treatment of intrauterine fetal infections.
      On the other hand, the placenta seems to produce an effective barrier reducing
      the fetal exposure when erythromycin is used exclusively to treat maternal
      infections.

PMID- 25775874
TI  - Analysis of clinical, biological and obstetric factors influencing the decision
      to perform cesarean myomectomy.
AB  - OBJECTIVES: Myomas in pregnancy are associated with a significantly higher risk
      for cesarean section (CS). Cesarean myomectomy (CM), i.e. myomectomy during
      cesarean section, has been the source of much debate and was considered
      relatively contraindicated for many years. However, some authors advise to
      perform routine myomectomy during CS. The aim of our study was to determine
      factors influencing the intraoperative decision to perform CM. MATERIAL AND
      METHODS: A total of 185 patients with uterine myomas, who delivered by caesarean
      section during a 5-year period, were included in the study--102 patients
      underwent CM (study group) and 83 women underwent CS without myomectomy (control
      group). Clinical and obstetric data were recorded and processed for analysis.
      Using non-parametric correlation methods, we investigated the influence of
      different variables on the decision to perform CM. RESULTS: No differences were
      recorded between the two groups in terms of parity fetal presentation,
      gestational age, number of previous laparotomies, and previous myomectomy
      presence of diabetes and hypertension, indications and type of CS. Significant
      differences were detected in type and location of the myomas, contrary to their
      number and size, where no significant differences were registered. CONCLUSIONS:
      The most significant predictors of CM included age, surgical experience and type
      of myomas. CM is generally performed by experienced surgeons and in younger
      women. Also, it is more often performed in patients affected by pedunculated and
      subserosal myomas, and less frequent in case of intramural and multiple myomas.

PMID- 25775875
TI  - [The 1691 G > A (factor V Leiden) and 1328 T > C V coagulation factor
      polymorphisms and recurrent miscarriages].
AB  - Objectives: Inherited thrombophilia might lead to recurrent pregnancy loss (RPL).
      The aim of the study was to estimate the prevalence of V coagulation factor
      polymorphisms related with inherited thrombophilia among women in Malopolska
      region.Material and methods: Group of 136 women, who experienced at least 2
      unexplained, idiopathic pregnancy loss. 106 healthy women having at least one
      uncomplicated pregnancy and delivered healthy children constituted a control
      group. Each patient were examined for factor V Leiden (FVL) and mutation 1328 T>C
      of factor V gene with use of real -time PCR and Taq-Man probes.Results: Among
      patients with RPL inhabiting region of Malopolska compared to control group
      occurred higher prevalence of FVL and mutation 1328 T>C. There is coincidence of
      polymorphism 1328 T>C of factor V gene and FVL in group of early and late
      RPL.Conclusions: TC genotype of 1328 T>C mutation carriers reveal tendency toward
      RPL below 7 weeks of pregnancy.Based on results of these findings inherited
      thrombophilia evaluation in patients after two or more RPL should be recommended.

PMID- 25775876
TI  - [Indications for hospitalization of young girls and adolescent girls--clinical
      work-up in the selected cases].
AB  - OBJECTIVE: The aim of the study was to analyze the clinical reasons for
      hospitalization due to gynecological causes of adolescent girls and young women.
      METHODS: We reviewed clinical data on reasons for hospitalization, treatment
      methods, and histopathological diagnosis in adolescent girls and young women
      hospitalized at the Second Department of Gynecology Medical University of Lublin,
      between January 2003 and December 2012. Methods of conservative or surgical
      treatment, as well as their clinical effectiveness, have been discussed. RESULTS:
      Over the analyzed period of time, we identified 334 patients at the age between 8
      and 20 years, which accounted for 1.61% of all hospitalized women during that
      time. Rating these patients by age, we found the following: 1 patient < 9 years
      old, 2 patients aged 10-11 years, 38 patients aged 12-14 years, 128 patients aged
      15-17 years and 165 patients aged 17-19 years old. The main clinical reasons for
      hospitalization of adolescents and young women due to gynecological causes were:
      ovarian cysts (138 cases; 41.3%), menstrual disorders (46 cases; 13.7%),
      pregnancy complications (35 cases; 10.5%), and congenital Mullerian anomalies (33
      cases; 9.9%). The remaining patients (24.6%) were admitted due to suspicion of
      ovarian cyst (22 cases; 6.6%), cervical erosion (15 cases; 4.5%), juvenile
      metrorrhagia (15 cases; 4.5%), and vulvar diseases (8 cases; 2.4%). CONCLUSIONS:
      Adolescent girls and young women are rarely admitted to gynecological
      departments. Nevertheless, they present a clinical challenge. Proper diagnosis
      using advanced visualization methods, along with modern pharmacotherapy accounts
      for the final therapeutic success.

PMID- 25775877
TI  - [PREVFNAIT prevention of foetal/neonatal alloimmune thrombocytopenia (FNAIT) in
      Polish foetuses and newborns--the PREVFNAIT program].
AB  - The scientific goals related to the grant include 1) estimation of FNAIT
      prevalence in Poland and 2) search for biomarkers to predict the risk of the
      antibody production and severity of fetal thrombocytopenia. Fetal/Neonatal
      Alloimmune Thrombocytopenia (FNAIT) is caused by destruction of fetal blood
      platelets due to maternal antibodies. This condition, which most commonly results
      from incompatibility between the mother and the fetus for the Human Platelet
      Antigen-1a (HPA-1a), may lead to intracranial hemorrhage, damage of the central
      nervous system (CNS) and even death of the fetus or the newborn. It can be the
      cause of strokes in term newborns. FNAIT is usually attributed to the presence of
      anti-HPA-1a antibodies. Its incidence rate is estimated at approximately 1/1000
      2000 live births. In the absence of a screening program, it is usually diagnosed
      after birth of a child with symptoms of thrombocytopenia or CNS hemorrhage.
      Monitoring of antibody production and thrombocytopenia treatment to effectively
      minimize the risk of stroke are therefore launched only at the next pregnancy.
      Testing indications are broader to include fetal ultrasound for symptoms of
      stroke to the CNS, ventricular enlargement or hydrocephalus, and obstetric
      failure. Diagnostic process is also recommended prior to the planned
      cordocentesis, in vitro fertilization and in sisters of mothers with children
      with FNAIT history. HPA-1a testing remains the best method for diagnosing
      pregnancies at risk. The detection frequency for FNAIT in Poland remains low.
      Therefore, the Institute of Hematology and Transfusion Medicine (IHTM) will have
      performed such HPA-1a antigen testing in 30 000 Polish women within the framework
      of the PREVFNAIT program by March 2016. HPA-1a negative women (2% of the
      population) are a risk group for production of anti- HPA-1a antibodies
      responsible for FNAIT therefore all of them will be monitored for the presence
      and activity of anti-HPA-1a antibodies. Such testing will be performed free of
      charge for the women.

PMID- 25775878
TI  - [Postpartum levator ani muscle injuries. Diagnosis and treatment].
AB  - Levator ani muscle (LAM) injuries are much more frequent than trauma to sphincter
      ani muscles, but so far they have been omitted in obstetric handbooks. Levator
      ani avulsion is observed only after vaginal delivery. Forceps delivery second
      stage of labor >= 110 min., fetal head circumference >= 35 cm, episiotomy and
      coincidence of anal sphincter trauma are risk factors for levator ani avulsion.
      The most vital issue in that type of trauma is pelvic organ prolapse and 2-4-fold
      higher risk of recurrence after prolapse surgery. The current level of evidence
      does not allow to conclusively determine the of role of levator avulsion in
      urinary incontinence. Levator injuries are occult, what constitutes the main
      diagnostic problem. Until recently magnetic resonance imaging has been the only
      diagnostic method until the development of 3-dimensional ultrasound. Nowadays, 3
      D ultrasound is an essential technique in static and functional diagnosis of the
      levator ani. There are no effective methods of levator trauma prevention. Except
      the risk factors reduction, there are some pilot data about positive role of
      antepartal perineal muscle training. Physiotherapy plays the main role in
      reducing the effects of levator trauma. Mesh techniques are the most effective
      operative methods in coincident pelvic organ prolapse with levator avulsion, but
      there is still a 2-fold higher risk of recurrence.

PMID- 25775879
TI  - [Maternity after breast cancer treatment].
AB  - Recent years have seen a notable increase in the number of breast cancer
      diagnoses among women who have not fulfilled their maternity plans before the
      disease. Cytotoxic drugs (chemotherapy), used in the treatment of breast cancer
      patients, cause varying degrees of damage to the ovaries. The expected favorable
      effect of gonadoliberin analogues on the preservation of fertility has not been
      confirmed in clinical trials, and these drugs are currently not recommended for
      therapy. It is only the development of cryobiology and assisted reproduction
      techniques that make it possible to preserve the reproductive potential. The
      safety of the mother and the baby after breast cancer treatment is a separate
      issue. The available data indicate that both, pregnancy and breast-feeding are
      safe for the mother and the baby. However, the majority of findings come from
      retrospective studies covering small sample size and excluding the heterogeneity
      of both, cancer cells and patient clinical data.

PMID- 25775880
TI  - [Acute urinary retention due to cervical myoma--a case report and a review of the
      literature].
AB  - CASE REPORT: A 48-year-old woman with acute urinary retention due to a big
      cervical leiomyoma pressing on the urethra was admitted to the Gynecologic Unit.
      A Foley catheterization was performed and 1500 mL of urine was drained. The
      gynecologic examination revealed a cervical tumor 10 cm in diameter. Acute
      urinary retention and intensifying abdominal pain were indications for emergency
      surgery. The presented case of obstructive urinary retention is a rare finding as
      the literature offers only single reports on the symptoms of cervical fibroids
      and the treatment methods. CONCLUSIONS: Cervical leiomyoma is a rare cause of
      acute urinary retention. The surgical procedure requires considerable experience
      to avoid intraoperative bleeding and bladder or bowel complications.

PMID- 25775881
TI  - [Comparison of low- and high-concentration (270 and 320 mg I/ml) iso-osmolar
      iodinated contrast media in coronary CT angiography: a randomized prospective
      single-center blinded study].
AB  - OBJECTIVE: To compare the image quality at coronary multidetector computed
      tomography (MDCT) using low-dose and low-iodine protocol study in comparison with
      the standard protocol. MATERIAL AND METHODS: In study included 60 patients
      undergoing coronary computed tomography angiography. All examinations were
      performed with 64-row MDCT using prospective ECG-gating and ASIR 40%. 30 patients
      were examined using a low-concentration (Iodixanol, 270 mg I/ml) iodinated
      contrast medium and low tube voltage (80 kV) (group 1), 30 patients--using of
      high-concentration (Iodixanol, 320 mg I/ml) iodinated contrast medium and
      standard tube voltage (120 kV) (group 2). Image quality of coronary arteries was
      evaluated using a four-point grading scale, images were randomised. Intra
      arterial density was measured for the proximal and distal segments of left
      anterior descending artery (LAD) and right coronary artery (RCA). RESULTS: Age,
      heart rate, BMI and scan parameters were not statistically different between the
      two groups. Analysis of coronaries visualization revealed the same image quality
      for group 1 and group 2 (image quality scores were 1.28 +/- 0.28 vs. 1.34 +/-
      0.29, p = 0.4). There was no significant difference between mean enhancement
      values in the distal segments of RCA and LAD for the two groups. Intraarterial
      density for proximal LAD and proximal RCA for the nazpyara, umepamuenas group 2
      were significantly lower (p < 0.05) than those values for the group 1.
      Conclusion. Theuse of low-dose and low-iodine protocol can be beneficial for
      patient safety and or image quality ithout loss of diag- stic information.

PMID- 25775882
TI  - [The first experience in using elastography in combination with endobronchial
      ultrasonography for mediastinal pathology: Preliminary assessment of feasibility
      and comparison of characteristics via different approaches].
AB  - OBJECTIVE: To preliminarily assess the feasibility of elastography in
      endobronchial ultrasonography and to compare characteristics via different
      accesses. MATERIAL AND METHODS: The investigation enrolled 3 patients (malignant,
      benign mediastinal adenopathy, paratracheal tumor). Elastography was carried out
      using a Pentax EB-1970UK echobronchoscope with a Hitachi Noblus ultrasound
      scanner. All the patients underwent fine-needle aspiration biopsy of mediastinal
      and pulmonary lymph nodes/masses with 22G needles (Cook, Medi-Globe). Sequential
      study of the same group of lymph nodes through different approaches through the
      esophagus and trachea was conducted, and its characteristics were compared in one
      patient. RESULTS: A total of 8 lymph nodes and one paratracheal mass (Group 4L-7
      4R-2R) were assessed in three patients. Reproducible images acceptable for visual
      assessment were obtained in all cases. The wall of the trachea and bronchi had no
      significant negative impact on the quality of an obtained image. Both malignant
      lesion of lymph nodes and paratracheal mass was accompanied by decreased tissue
      elasticity in the area of interest. Assessment of the same benign lymph node
      through different approaches revealed a clear discordance between elastographic
      findings with a drastic decrease in elasticity values via an endobronchial
      approach. CONCLUSION: Endobronchial ultrasonography elastography is technically
      feasible. The wall of the trachea and bronchi has no significant impact on the
      quality of an obtained image; elastographic data are reproducible during re
      measurements. Comparison of elastographic characteristics through different
      approaches suggests that there is a tendency to overestimate data on lymph node
      density during endobronchial examination versus a transesophageal approach. Thus,
      the direct transfer of the accumulated data and patterns of elastographic
      diagnosis to an endobronchial approach is impossible and likely to require a
      revision of criteria to estimate malignancy-associated changes during its
      application.

PMID- 25775883
TI  - [Diagnostic efficiency of multidetector computed tomography in patients with
      tongue cancer].
AB  - OBJECTIVE: To determine the capacities of multidetector computed tomography
      (MDCT) to diagnose tongue cancer. MATERIAL AND METHODS: Intravenous bolus
      contrast-enhanced MDCT was performed in 40 patients with tongue cancer diagnosed
      during complex clinical and instrumental examination. In all cases, the tumor had
      a structure of squamous cell carcinoma of varying grades. The results of MSCT
      were compared with the data of surgery and cytological and histological
      examinations. Tongue tumor accumulation of a contrast agent was qualitatively
      analyzed. RESULTS: In 38 (85%) patients, the tongue tumor actively accumulated
      the contrast agent and was clearly differentiated in the presence of unaffected
      portions of the tongue and other adjacent anatomical structures, such as mouth
      floor, oropharynx, and larynx. Only in two cases, the tumor failed to
      significantly accumulate the contrast agent, which was associated with that there
      were massive decay areas in its structure. The sensitivity, specificity, and
      accuracy of MDCT in the diagnosis of tongue cancer were 95, 80, and 87.5%,
      respectively. MDCT could reliably differentiate changes in tongue cancer from non
      tumor diseases. The result of constructing the curve of diagnostic errors became
      the following values: the area under the curve was 0.875 and the P-value
      (Asymptotic Sig.) was 0.0001. CONCLUSION: Intravenous bolus contrast-enhanced
      MDCT has a high diagnostic efficiency in identifying tongue cancer. The technique
      can establish the location of a tumor and to reveal the extent of the process to
      the nearby organs.

PMID- 25775884
TI  - [Computed tomography pattern of unchanged mediastinal lymph nodes in children
      with uninfected Mycobacterium tuberculosis].
AB  - OBJECTIVE: To provide X-ray characteristics of mediastinal lymph nodes revealed
      by computed tomography (CT) in children and adolescents with uninfected
      Mycobacterium tuberculosis. MATERIAL AND METHODS: The basis of the study was the
      results of CT in 105 children and adolescents with uninfected with Mycobacterium
      tuberculosis. All the children and adolescents from a follow-up group underwent X
      ray study using a two-slice spiral Somatom Emotion Duo CT scanner (Siemens). The
      study used a conventional procedure for chest scanning in children, by applying
      the Thorax Routine program. RESULTS: The study ascertained that Groups 1-3
      intrathoracic lymph nodes were visualized in 73.3% of the children in normalcy
      and were not in 22.8%. In children, the normal size of the lymph nodes did not
      exceed 0.8 cm in diameter; they had a homogeneous structure and clearly defined,
      even outlines; their perinodular fat was unchanged. CT data showed that the sizes
      and number of visible groups of lymph nodes were unrelated to age. CONCLUSION:
      The upper diameter limit for normal mediastinal lymph nodes may be established to
      be 8 mm if there were no abnormal changes in the structure of lymph nodes and
      perinodular fat.

PMID- 25775885
TI  - [Role of magnetic resonance imaging in the study of patients with diabetic foot
      syndrome].
AB  - OBJECTIVE: To give the results of magnetic resonance imaging (MRI) in patients
      with complicated diabetic foot syndrome (DFS) to rule out or identify
      osteomyelitis. MATERIAL AND METHODS: Twenty-seven (14 women and 13 men; mean age
      60 +/- 12.2 years) with type 1 and 2 diabetes mellitus and suspected
      osteomyelitis that had developed in the presence of DFS were examined. Ankle
      joint and foot MRI was carried out in T1-weighted MR image, T2-weighed MRI image,
      and FSat sequences. The soft tissue, tendoligamentous apparatus, and bones were
      evaluated. The results of MRI were compared with the data of a clinical follow-up
      study and surgery, followed by morphological examination. The diagnosis of
      osteomyelitis was validly established in 7 cases; this disease was absent in 20
      patients. RESULTS: MRI showed the highest sensitivity for bone marrow edema
      (100%), soft tissue swelling (85.7%), and their concurrence (85.7%) and the
      highest specificity for an extensive wound defect or fistula attached to the bone
      (100%) and bone marrow edema concurrent with tenosynovitis (90%). With a
      sensitivity of 14.3% and a specificity of 10%, MRI was of less informative value
      in assessing bone destruction. It was characterized by moderate sensitivity and
      moderate specificity for soft tissue destruction (57.1 and 42.9%, respectively)
      and tenosynovitis (55 and 50%, respectively). CONCLUSION: Osteomyelitis MRI
      demonstrated a polymorphic pattern with different diagnostic efficiency for
      individual symptoms.

PMID- 25775886
TI  - [Prognostic value of 18F-FDG positron emission tomography in the early evaluation
      of the efficiency of treatment in patients with non-Hodgkin lymphomas].
AB  - OBJECTIVE: To define the role of 18F-FDG positron emission tomography (PET)
      performed after 2-3 chemotherapy cycles in the prediction of disease prognosis
      and to identify a group of patients requiring more intensive treatment. MATERIAL
      AND METHODS: Seventy-one patients with non-Hodgkin lymphoma of different
      histological types were examined. PET was carried out at different stages of
      diagnosis and primary treatment in the patients. RESULTS: The examinations made
      after 2-3 polychemotherapy (PCT) cycles indicated that 36 (50.7%) patients
      continued to have signs of metabolic activity of lymphoproliferative disease (a
      PET-positive group) and 35 (49.3%) patients were found to have no abnormal tracer
      accumulation foci (a PET-negative group). Twenty-nine (82.9%) patients from the
      PET-negative group continued to remain in complete remission throughout the
      follow-up (the median follow-up was 405 days). At late stages, 6 (17.1%) patients
      were identified to have abnormal tracer hyperfixation foci that were indicative
      of disease recurrence. Only 8 patients from the PET-positive group were observed
      to show a complete metabolic response to treatment at the end of first-line PCT.
      The metabolic activity of the disease was maintained in the remaining patients.
      The results of PET conducted at the late stages of the follow-up indicated that
      metabolically active tumor foci continued to be visualized in 20 (55.6%) patients
      and further treatment resulted in complete remission in 16 (44.4%) patients.
      CONCLUSION: PET findings could predict the further course of the disease and
      differentiate more intensive treatment-requiring patients at the early stages of
      chemotherapy.

PMID- 25775887
TI  - [Embolization of mammary artery branches after mammary artery bypass surgery].
AB  - Even after performed mammary artery bypass surgery, some patients continued to
      have clinical manifestations of angina pectoris. This may be associated with the
      development of coronary stealing syndrome due to the fact that the native
      intrathoracic artery has large lateral branches. Current methods for embolization
      of arteries of different diameters make it possible to accomplish this task
      reasonably safely and in full measure. This paper describes a clinical case of
      reembolization of the lateral branch of a mammary artery shunt with an
      intravascular coil.

PMID- 25775888
TI  - [Use of BI-RADS to interpret magnetic resonance mammography for breast cancer].
AB  - The Breast Imaging Reporting and Data System (BI-RADS) is a practical tool
      developed by the American College of Radiology to standardize the description of
      mammography, ultrasound study, and magnetic resonance mammography. BI-RADS
      includes recommendations for the structure of a protocol to describe radiologic
      studies; terminology to characterize three major types of lesions (focus, mass,
      contrasting area); as well as assessment categories and their corresponding
      recommendations for further patient management. The publication gives general
      information on the new edition of BI-RADS (2013) and illustrates its use to
      interpret magnetic resonance mammograms in breast cancer. The wider introduction
      of BI-RADS at all stages from screening to diagnostic verification will improve
      the quality of diagnosis and prognosis in breast tumor diseases.

PMID- 25775889
TI  - [History of the development of radiodiagnosis at the Russian Research Center of
      Roentgenology and Radiology: on the occasion of the 90th anniversary of its
      foundation].
AB  - The paper describes the history of the Russian Research Center of Roentgenology
      and Radiology set up 90 years ago, the main advances of the researchers of the
      Institute in roentgenology and radiodiagnosis in historical perspective--from the
      last century up to the present day. It gives a brief list of the most important
      procedures and publications on radiodiagnosis, which have been developed and
      published by the Institute's researchers.

PMID- 25775890
TI  - [Differential diagnosis of brain gliomas by positron emission tomography using
      various radiopharmaceuticals].
AB  - OBJECTIVE: To comparatively study the diagnostic capabilities of positron
      emission tomography (PET) with various tumorotropic radiopharmaceuticals (TRPs)
      in detecting malignant brain gliomas (BG) and estimating their degree. MATERIAL
      AND METHODS: One hundred and fourteen patients, including 47 with histologically
      verified glioblastoma multiforme (GBM), 27 with anaplastic astrocytoma (AA), 23
      with benign astrocytoma (BA), and 17 with postoperative cysts, were examined. PET
      was performed using TRPs: 18F-fluorodesoxyglucose (18F-FDG), 11C-sodium butyrate
      (11C-SB), 11C-L-methionine (11C-MET), and 11C-choline (11C-COL). RESULTS:
      Malignant gliomas (GBM and AA) were clearly visualized by PET using 11C-MET, 11C
      CHOL, and 11C-SB. 18F-FDG PET visualization of tumors was difficult because of
      increased RP accumulation in the cerebral cortex. WHO grades II-III gliomas were
      completely visualized by 11C-MET PET. Only some tumors were clearly displayed by
      PET with 11C-CHOL and 11C-SB. The accumulation indices (AI) obtained by 11C-CHOL
      PET in patients with malignant gliomas were, on average, 4.0- and 5.5-fold higher
      than those by 11C-MET and 11C-SB PET, respectively. Significant differences (p <
      0.001) in AI obtained by "C-CHOL ("C-CHOL-AI) PET were first established between
      the patients with GBM (WHO grade IV) and those with AA (WHO grade III).
      CONCLUSION: 11C-CHOL PET is the most sensitive method to identify gliomas and
      estimate their grade. The advantage of 11C-MET PET is the possible imaging of the
      entire volume of viable tumor tissue.

PMID- 25775891
TI  - [The persistent trigeminal artery as evidenced by multislice spiral computed
      tomographic angiography].
AB  - OBJECTIVE: To determine the incidence of the persistent trigeminal artery (PTA)
      and to reveal its relationship to cerebral aneurysms, as well as the concomitant
      anatomic features of cerebral arteries according to the data of multislice spiral
      computed tomographic angiography (CTA). MATERIAL AND METHODS. A total of 1041
      patients underwent brachiocephalic artery CTA according to different clinical
      indications. PTA and cerebral arterial aneurysms were found on the computed
      tomographic angiograms and the anatomic features of the structure of the circle
      of Willis were assessed. RESULTS: PTA was identified in 6 (0.58%) of the 1041
      patients. Cerebral aneurysm was present in only one patient with PTA and
      concurrent with hypoplasia of the contralateral A1 segment of the anterior
      cerebral artery. Hypoplasia of the basilar artery (BA) and both vertebral
      arteries (VA) was observed in 3 (60%) cases, with the diameter of PTA at its
      confluence with BA exceeding 3 mm. When the diameter of BA was normal, that of
      PTA was less than 2 mm. All PTAs were wider at their base, by decreasing in
      diameters distally. CONCLUSION: CTA showed that the incidence of PTA was 0.58%
      and its lateral type according to the Salas classification and Saltzman's type 1
      were more common (5/6). In 4 cases, PTA was concurrent with VA and BA hypoplasia,
      with its degree being inversely related to the distal diameter of PTA. There was
      no convincing evidence for a relationship of PTA to cerebral aneurysms.

PMID- 25775892
TI  - [Efficiency of ultrasound study in the diagnosis of cholangiocellular carcinoma].
AB  - OBJECTIVE: To evaluate the efficiency of ultrasound diagnosis in detecting and
      staging cholangiocellular carcinoma. MATERIAL AND METHODS: An ultrasound study
      (USS) was conducted in 120 patients aged 19 to 84 years with cholangiocellular
      carcinoma. The patients were divided into 3 groups by the location of a tumor
      process: 1) 47 (39.2%) patients with intrahepatic tumor; 2) 49 (40.8%) with
      portal duct or Klatskin's tumor; 3) 24 (20%) with distal one. Ninety (75%)
      patients were operated on; the others underwent minimally invasive X-ray surgical
      interventions as percutaneous transhepatic cholangiostomies. The data of
      ultrasound diagnosis were compared with the results of other studies,
      intraoperative assessment and morphological examination of a removed gross
      specimen. RESULTS: A tumor was detectable by USS only in 90 (75%) patients; its
      sensitivity was 100% for intrahepatic cholangiocellular carcinoma; 69.4 and 37.5%
      for portal duct and distal ones, respectively. It is most difficult to diagnose
      distal carcinomas of the common bile duct. USS reveals no semiotic signs of
      intrahepatic cholangiocellular carcinoma, which could distinguish the latter from
      other liver cancers. The specific features of the infiltrative growth of a bile
      duct tumor, such as hyperechoic infiltration along the external outlines of the
      ducts or hypoechoic infiltration during thickening of the duct walls, were
      ascertained. The sensitivity of intraoperative USS in identifying intrahepatic
      and portal duct cholangiocarcinoma was 100%. That of USS in detecting lymph node
      metastases was 61%; developed the semiotics of altered metastatic lymph nodes.
      CONCLUSION: The findings have indicated the high informative value of ultrasound
      diagnosis in determining the dilatation of the bile ducts and the spread of a
      tumor to the liver and lymph nodes. It is recommended that the indications for
      intraoperative USS should be expanded in intrahepatic cholangiocellular carcinoma
      to define the extent of duct carcinoma.

PMID- 25775893
TI  - [Capabilities of computed tomography to evaluate polymorphic changes in
      destructive pancreatitis].
AB  - OBJECTIVE: To determine whether the lower-density pancreatic parenchymal areas
      detected by a computed tomography (CT) study in patients with acute pancreatitis
      correspond to the necrotic portions of the gland or whether these changes may be
      reversal. MATERIAL AND METHODS: The investigation covered 25 patients who had
      undergone or dynamic CT studies made at different time intervals. Two independent
      investigators with 4 and 19 years of experience retrospectively analyzed the
      results of both CT studies. Target estimation was made of the extent (volume) of
      and CT density changes in the hypodense areas of the gland parenchyma. RESULTS:
      Seven (28%) of the 25 patients were noted to have higher CT density in the areas
      that had decreased density during primary CT studies (more than a 30 HU increase
      was rated as significant). There was a statistically significant difference
      between the patient groups when comparing the extent of hypodense areas and the
      difference in CT density (t-test, p = 0.006); Mann-Whitney U-test, p = 0.01 for
      extent difference and t-test, p = 0.00; Mann-Whitney U-test, p = 0.00 for CT
      density difference. There was also a correlation between the extent of hypodense
      areas and the difference in their CT density (Pearson: r = -0.533, p = 0.006;
      Spearman: r = -0.636, p = 0.001). CONCLUSION: The results of our investigation
      may suggest that the lower-density pancreatic parenchymal areas cannot always
      correspond to necrotic changes and may be reversible.

PMID- 25775894
TI  - [Ultrasound monitoring of consolidation processes in fractures of long tubular
      bones in osteosynthesis using bioactive implants].
AB  - OBJECTIVE: To show the capabilities of ultrasound monitoring to assess
      consolidation processes in fractures of long tubular bones in the use of
      bioactive material-containing implants. MATERIAL AND METHODS: Eighty-two (45.1%)
      patients whose bone fragments had been fixed with bioactive material-coated
      plates and 100 (54.9%) patients with bioinert material-coated ones were examined.
      Consolidation changes were estimated by ultrasound and X-ray studies 2, 4, 6, and
      12 months after surgery. Bone metabolic changes were determined by US osteometry
      2 months following surgery. Ultrasound data were compared with the biochemical
      markers: C-terminal telopeptide (CrossLaps) and osteocalcin. RESULTS AND
      CONCLUSIONS: Ultrasound monitoring of the rates of consolidation and the time
      course of changes in bone strength versus the biochemical markers established the
      positive effect of bioactiveplates on the process of consolidation in fractures
      of tubular bones and made it possible to consider local osteopenic syndrome to be
      a prognostically favorable sign of timely callus formation.

PMID- 25775895
TI  - [Cone-beam computed tomography in paleoanthropology].
AB  - OBJECTIVE: To study the capabilities of cone-bean computed tomography (CBCT) in
      estimating the bone structure when analyzing anthropological findings. MATERIAL
      AND METHODS: Twenty-four bone fragments (remains) of Napoleon Bonaparte Imperial
      Army soldiers who had died at a Konigsberg military hospital during their retreat
      from Russia in the War of 1812 were examined by CBCT. A total of 28 tubular bones
      with different injury healing signs and a skull with maxillofacial trauma marks
      were investigated. Furthermore, an object from D.G. Rokhlin's paleopathological
      collection was used to analyze a complicated humeral infectious process. CBCT was
      performed by individually selecting the scanning foldings, physicotechnical
      conditions and regimens in relation to the anatomic location and size of
      fragments. RESULTS: Processing of the obtained images reveled fractures of
      different bones in 19 (65.5%) cases. The signs of ununited fractures were
      visualized in 20.7% of the samples. Image post-processing showed intraarticular
      consolidated fractures in 13.8% of the anthropological findings. The CBCT
      examination of bone fragments exhibited the signs of their fusion. A wound
      pattern was established in 31% of the samples. The specific features of a bone
      amputation stump could be characterized in detail in 17.2% of the anthropological
      findings. 51.7% of the cases were found to have signs of sustained bone
      inflammatory diseases of various genesis, which in 41.4% of them were presented
      by linear, bulbar, and assimilated periostal reactions and significantly
      detectable on CBCT scans. Sequestral cavities were imaged in 31% of the
      fragments. CONCLUSION: The CBCT images are characterized by high informative
      value (from 7.5 to 10.6 pixels/mm), optimal spatial resolution, definition, and
      hardness. The software of CBCT involves the parameters and possible
      postprocessing of images (building of panoramic and mulplanar reconstructions,
      assessment of the density characteristics of tissues), which allow an analysis of
      anthropological material, by needlessly destroying them.

PMID- 25775896
TI  - [Cardiac magnetic resonance imaging in the diagnosis of acute myocarditis: a
      clinical case and a review of literature].
AB  - The clinical manifestations of myocarditis are extremely variable and it may
      commonly manifest as acute myocardial infarction. The diagnosis of acute
      myocarditis is frequently empiric and substantiated by the clinical picture of
      the disease, ECG changes, elevated enzyme levels, and the lack of any data on
      coronary heart disease. Until recently, endomyocardial biopsy has been considered
      to be the most accurate diagnostic method. However, endomyocardial biopsy has a
      low sensitivity and is associated with the high risk of complications. This paper
      describes a clinical case of a patient with cardialgias occurring after acute
      respiratory viral disease, with ST segment elevation, and higher levels of
      cardiospecific enzymes. The diagnosis of myocarditis was verified by contrast
      enhanced cardiac magnetic resonance imaging.

PMID- 25775897
TI  - [Endovascular treatment for chronic coronary occlusions in patients with coronary
      heart disease].
AB  - OBJECTIVE: To analyze the angiographic results of endovascular treatment for
      chronic coronary occlusions in patients with coronary heart disease. MATERIAL AND
      METHODS: In 2009 to 2013 attempted endovascu-ar recanalization of chronic
      coronary occlusions in 854 patients with coronary heart disease. The patients'
      age ranged from3 6 to 68 years (mean 52 years). The estimated du-ation of
      occlusion was m1 onth to more than 3 years. There were 193 (22.6%) females and
      661 (77.4%) males. 462 (54.1%) patients had a history of myocardial infarction.
      738 (86.4%) and 116 (13.6%) patients had true (TIMI grade 0) and functional (TIMI
      grade i1 occlusions, respectively. Multi- and univascular lesions were found in
      683 (79.9%) and 171 (20.1%) patients, respectively. Silent occlusions with
      preserved myocardial contractility were identified in 165 (19.3%) patients.
      RRESULTS:Blood flow could be successfully restored in 616 (72.1%) patients.
      Recanalization of chronic coronary occlusion failed in 238 (27.9%) patients.
      CCONCLUSION:Recanalization of chronic coronary occlusions is a highly effective
      and relatively safe technique. The efficiency of the procedure largely depends on
      the duration of occlusion, its X-ray morphological characteristics, and the
      experience of a physician.

PMID- 25775898
TI  - [Stable isotope diagnostics in Russia; results and prospects, 13C-preparations,
      instruments, methods].
AB  - The basis of the highly effective method for diagnostics of many dangerous
      diseases with the use of breathing tests and stable 13C isotope-labeled
      preparations has been developed in Russia during the past years. The technology
      for manufacturing 13C-preparations using domestically produced starting materials
      satisfies the requirements for isotopes in this and many foreign countries. New
      instruments for respiratory tests and diagnostic methods make it possible to
      carry out diagnostics in large populations including that in the course of
      regular medical examination. This paper reports high efficacy of 13C-based breath
      tests for diagnostics of gastrointestinal disorders, possibilities and prospects
      for their further application in oncology, endocrinology, pulmonology, neurology,
      cardiology, surgery, etc. Special attention is given to the use of 13C-magnetic
      resonance techniques for visualization of tumours and blood vessels, studies of
      metabolic processes and energy balance in man and animals with the use of 13C
      biomarkers. The main advantages of these new diagnostic approaches are high
      accuracy, safety (for both patients and personnel), simplicity, and possibility
      of application in different fields of medicine.

PMID- 25775899
TI  - [Current views of psychosomatic diseases].
AB  - This review is designed to analyse current views of physicians representing
      different fields of medicine (psychoanalysis, pathological anatomy, psychiatry,
      etc.) on the problem of psychosomatic diseases with reference to its history,
      past and present concepts, etiopathogenetic mechanisms of these conditions. The
      authors propose to use the results of analysis as a basis for considering
      psychosomatic diseases as a singular etiopathogenetic entity resulting from
      dysregulation of rhythm-organizing structures.

PMID- 25775900
TI  - [Irritated bowel syndrome: what is its real nature?].
AB  - The author discusses definition of irritated bowel syndrome (IBS), the history of
      this problem and terminological issues. Current views of IBS etiology and
      pathogenesis are presented with special reference to the biopsychosocial concept
      of this condition. Clinical variants of IBS are described along with its
      intestinal and extraintestinal symptoms and their classification. Modern methods
      of laboratory, instrumental, and differential diagnostics of IBS are considered
      alongside with the "anxiety symptoms" excluding diagnosis of IBS. The review is
      concluded by the description of methods for psychotherapeutic and
      pharmacotherapeutic treatment of the disease. Much attention is given to the
      meaning of the term irritated bowel syndrome, impermissibility of
      "nosologization" of syndromes and impossibility of functional disorders without
      their morphological equivalent as illustrated by the latest data on the IBS
      associated inflammatory process in the colon.

PMID- 25775901
TI  - [Functional disorders of the gastrointestinal tract in the context of
      morphofunctional unity].
AB  - The aim of this work was systematization of the currently available data on
      pathological physiology and morphology of functional disorders of the
      gastrointestinal tract (GIT) underlain by combined changes of neuroendocrine and
      neural regulation related to genetic polymorphism and external provoking factors
      (in the first place, stress). Altered function and morphology of diffuse
      neuroendocrine system and expression of certain regulatory molecules (nitric
      oxide, interleukin-1) in the patients with functional GIT disorders induce
      inflammation and changes in epitheliocyte regeneration, i.e. morphological
      substrate of the disease. Verification of various morphofunctional and structural
      changes accompanying functional pathology of GIT necessitates further improvement
      of classification criteria for functional diseases as reflected in the
      forthcoming Rome criteria IV.

PMID- 25775902
TI  - [Disordered diastolic function of the left ventricle in patients with coronary
      heart disease depending on ejection fraction].
AB  - The authors present data on the occurrence of different types of left ventricular
      diastolic function in patients with coronary heart disease collected in the
      course of population-based epidemiological study. The diastolic function was
      evaluated from parameters of transmitral blood flow depending on ejection
      fraction.

PMID- 25775903
TI  - [The cytoprotective role of endogenous heat shock proteins during the treatment
      of patients with acute coronary syndrome].
AB  - The study involving 48 patients with the preliminary diagnosis of acute coronary
      syndrome aged 54-78 years included analysis of clinical, laboratory and
      instrumental data for subgroups with different definitive diagnosis (myocardial
      infarction and unstable angina in 28 and 22 patients respectively). On the whole,
      the mean content of HSP-70 at admission averaged 2.1 +/- 0.3 ng/ml and decreased
      to 1.6 +/- 0.4 ng/ml (p < 0.05) after therapy. In the subgroup with myocardial
      infarction, the HSP-70 level (1.6 +/- 0.4 ng/ml) was significantly lower than in
      patients with unstable angina (2.1 +/- 0.3 ng/ml); p < 0.05. The reduced HSP-70
      level associated with a severe myocardial lesion gives evidence against the
      hypothesis of these proteins as markers of myocardial dysfunction whereas a rise
      in their content at the onset of ischemic process suggests their protective role.

PMID- 25775904
TI  - [Analysis of effects of pharmacotherapy on certain parameters of clinical
      laboratory diagnostics].
AB  - AIM: To study effects of pharmaceutical products on the results of clinical and
      laboratory diagnostics. MATERIALS AND METHODS: The list of vitally important
      pharmaceuticals, clinico-pharmacological articles of the National registry of
      medicinal products, formulary articles from the Federal guidelines on the use of
      pharmaceutical products. Formulary system, instructions for use of individual
      pharmaceutical products. Systemic and information-based approaches, logical and
      comparative analysis were used throughout the study. RESULTS: Results of analysis
      enabled the authors to draw up separate lists of pharmaceuticals based on their
      influence on parameters of clinical laboratory diagnostics, such as the list of
      pharmaceuticals exerting marked effect on diagnostic characteristics (blood
      properties, primary and coagulative hemostasis, serum enzymes), the list of
      pharmaceuticals exerting marked effect on systematized laboratory
      characteristics; the list of pharmaceuticals exerting no effect on clinical and
      laboratory diagnostics; the list of pharmaceuticals whose effect on diagnostic
      characteristics awaits clarification. CONCLUSION: The results of the study can be
      used for the development of recommendations on pharmaceutical counseling and
      rational choice of pharmaceutical products being prescribed to concrete patients.

PMID- 25775905
TI  - [Familial hypercholesterolemia due to a new mutation in the low density
      lipoprotein receptor gene].
AB  - Familial hypercholesterolemia (FHC) is a genetic disorder manifest as a rise in
      serum cholesterol level responsible for the development ofcardiovascular
      diseases. AIM: To study genetic peculiarities of FHC in Kareliya. MATERIALS AND
      METHODS: 109 patients of the 196 ones with FHC (124 families) were subjected to
      genetic examination. Other parameters studied included the lipid spectrum, blood
      glucose level, ECG, 24 hr ECG monitoring, echocardiography, triplex scanning of
      brachiocephalic arteries and lower limb vessels, functional tests. Simon Broom
      criteria were used to diagnose FHC. RESULTS: "Definitive" FHC was diagnosed in
      136 (69.4%) patients, (probable) FHC in 30.6%. The total encoding region of the
      low density lipoprotein receptor gene was sequenced in 109 (55.6%) patients in
      parallel with the search for major mutations in the APOB and PCSK9 genes. A total
      of 13 mutations (p.G20R, c. 192del110/ins8, c.195-196insT, p.S206R, c925-
      931del17, p.S447C, p.13981, p.L426P, L511S, c.1686del18/insT, p.L646I, p.N640N,
      c.2191delG) were identified in low density lipoprotein receptor gene; seven of
      them are reported for the first time in the world. No major mutations in the APOB
      and PCSK9 genes were found. The new c.2191delG (p.(Val73 1Serfs*6)) mutation is
      characterized and its segregation with familial dyslipidemia is shown. The
      present case is characterized by the absence of clinical picture of coronary
      heart disease and the family history complicated by cerebral basin lesion.
      Phenotypic manifestations of atherosclerosis in FHC with gene mutations need
      further studies.

PMID- 25775906
TI  - [Molecular-genetic methods for diagnostics of tumour growth].
AB  - Considerable progress has recently been achieved in understanding molecular
      medicine in general and vell molecular biology in particular. Molecular medicine
      is a scientific discipline studying man under normal condition and pathological
      changes at the cellular-molecular level with reference to gene activity and
      function of protein mediators responsible for delivery of information to various
      organs or systems of the body and cell-to-cell interaction.

PMID- 25775907
TI  - [The relationship between EGFR mutation and clinico-pathological features of lung
      adenocarcinoma in residents of southern Russia].
AB  - The study was designed to analyse the relationship between EGFR mutation and
      clinico-pathological features of lung adenocarcinoma in residents of southern
      Russia taking account oftheir age and sex, localization of the primary tumour,
      its cell differentiation, regional metastases, stage of disease and smoking
      status of the patients with mutant and wild-type EGFR genes. The frequency
      analysis included 29 somatic mutations in EGFR exones 18-21. The study revealed
      statistically significant associations of EGFR gene mutations with gender,
      smoking and stage of disease.

PMID- 25775908
TI  - [On the cause of F. M. Dostoevsky's death].
AB  - Opinions of F. M. Dostoevsky's death as resulting from "...throat bleeding..."
      associated with bronchopulmonary pathology differ and have no solid basis. In
      order to clarify mechanisms behind fatal "...throat bleeding...", we systematized
      the data pertaining to possible pathology and undertook retrospective
      differential diagnostic analysis of the case history taking account of the
      patient's description of his health conditions, notes made by the writer after
      counseling with doctors, and observations of his relatives. Main attention was
      given to lung diseases that could possibly provoke "... throat bleeding..." In
      contrast to the generally accepted view we failed to obtain convincing evidence
      that this condition was responsible for the lethal outcome. New versions of the
      cause and mechanism of F. M. Dostoevsky's death are proposed, but none of them
      has yet been definitely proved.

PMID- 25775909
TI  - [Effectiveness of pharmacotherapy of irritated bowel syndrome from the standpoint
      of evidence based medicine].
AB  - Evaluation of the action of various medicines used to treat irritated bowel
      syndrome from the standpoint of evidence based medicine indicates that most of
      them (spasmolytics, probiotics, loperamide, aperients) show but low
      effectiveness. The use of more efficacious preparations (alosterone, cisapride,
      tegacerode) is associated with serious adverse reactions whereas prucalopride is
      applied for unregistered indications. It necessitates the development of new
      drugs with enhanced effectiveness and tolerability.

PMID- 25775910
TI  - [Clinical and morphological aspects of infectious endocarditis].
AB  - Comparative analysis of anamnestic, clinical, laboratory and instrumental data
      involved 106 patients with infectious endocarditis treated in S.P. Botkin City
      Clinical Hospital in 2000-2011 and 92 ones admitted in 1985-1977. The results
      give evidence of ongoing pathomorphosis of infectious endocarditis as is apparent
      from the growing number of male patients, increased frequency of primary cases
      and previous invasive or intravascular manipulations, thromboembolic
      complications including pulmonary thromboembolism, right heart chamber
      endocarditis. Over half of the patients are socially unadapted C-peptide level is
      of diagnostic value for the assessment of inflammation activity, precursors of
      natriuretic peptide can be used to detect preclinical and clinical stages of
      cardiac failure related to infectious endocarditis. There is correlation between
      severity of inflammation and myocardial dysfunction. Early surgical intervention
      in the absence of effect of combined antibacterial therapy improves prognosis.
      Morphological studies of inflammation-related changes in myocardium, destruction
      of cardiomyocytes, dystrophic processes, and fibrosis play an important role in
      the development of cardiac insufficiency and prognosis of infectious
      endocarditis.

PMID- 25775911
TI  - [Ormond's disease complicated by infectious endocarditis].
AB  - A case of retroperitoneal fibrosis (Ormond's disease) is reported. It is known to
      be usually diagnosed at the late stages of renal complications Urinary infection
      ended in infectious endocarditis caused by E. faecium showing multiple resistance
      to antibiotics. Moderate immunosuppressive and modern antibacterial (daptomycin)
      therapy ensured remission of both Ormond's diseases and endocarditis.

PMID- 25775912
TI  - [The wound and death of the Russian military commander P.I. Bagration. Part 1].

PMID- 25775913
TI  - Margaret McCartney: drugs with anticholinergic side effects and cognitive decline
      -cause or effect?

PMID- 25775914
TI  - Family Rituals and Quality of Life in Children With Cancer and Their Parents: The
      Role of Family Cohesion and Hope.
AB  - OBJECTIVE: Family rituals are associated with adaptive functioning in pediatric
      illness, including quality of life (QoL). This article explores the role of
      family cohesion and hope as mediators of this association in children with cancer
      and their parents. METHODS: Portuguese children with cancer (N = 389), on- and
      off-treatment, and one of their parents completed self-report measures.
      Structural equation modeling was used to examine direct and indirect links
      between family rituals and QoL. RESULTS: When children and parents reported
      higher levels of family rituals, they also reported more family cohesion and
      hope, which were linked to better QoL. At the dyadic level, children's QoL was
      related to parents' family rituals through the child's family cohesion. This
      model was valid across child's age-group, treatment status, and socioeconomic
      status. CONCLUSIONS: Family rituals are important in promoting QoL in pediatric
      cancer via family cohesion and hope individually and via family cohesion in terms
      of parent-child interactions.

PMID- 25775915
TI  - Secular trends in average height and age at menarche of ethnic Russians and Komi
      Permyaks of the Permsky Krai, Russia.
AB  - The aim was to describe the changes in body size and age at menarche in
      anthropologically distinct ethnic groups - Komi-Permyaks (KP) and Russians (RU) -
      of Permsky Krai that occurred in the last century, with a special concern to the
      urban-rural differences. The comparison of the 1861 - 1865 and 1990 birth cohorts
      (BiCo) revealed following results. In RU rural males the increase in stature (ST)
      was 10.8 cm (p < 0.001). The chest circumference has increased by 5.9 cm, but it
      is unsubstantial 0.25 % when measured in relative to ST values. In RU urban males
      the overall increase in ST was 10.8 cm (p < 0.001), chest circumference increased
      by 10.5 cm. The peak increase in ST (+1.36 cm per decade) was attained between
      the 1964 and the 1990 BiCo. The data on body dimensions of RU females available
      only from the 1960s to 1990. The ST of rural females has not changed, but the
      absolute and the relative (to ST) values of pelvic width of the 1980 - 1989 BiCo
      are significantly (p < 0.05) lower than in the 1966 - 1975 and 1965 BiCo. The RU
      urban females of the 1985 BiCo are 3.6 cm taller than 1964 BiCo (p < 0.001), but
      over the next 5 years the ST decreased by 2 cm (p = 0.06). The relative pelvic
      width has decreased from 17.57 % (BiCo 1965 - 1969) to 17.18 % (BiCo 1980 - 1989;
      p < 0.05). Menarcheal age of Perm females declined from 14.5 yrs in the 1930 -
      1939 BiCo to 13.3 yrs in 1950 - 1965 BiCo, then ceased to change. The changes
      across generations in rural KP were weak. The rural males born in 1885 were 2.1
      cm taller than BiCo 1861 - 1865. From the 1925 to 1975 BiCo the average ST
      increased by 6.2 cm (1.24 cm/decade). KP rural females became 6.4 cm taller from
      the 1885 to 1985 BiCo. Pelvic width in the 1985 BiCo (27.4 cm) is significantly
      bigger (p < 0.05) than in the 1975 BiCo (26.9 cm). The changes in ST of urban KP
      females were more obvious than in rural groups. The 1985 BiCo of urban KP females
      (ST 161.8 cm) are taller than those born in 1965 (159.4 cm; p < 0.05), but their
      pelvic width does not differ. In urban and rural KP females age at menarche is
      earlier in the 1976 - 1985 than in the 1966 - 1975 BiCo (p < 0.01). In all the KP
      cohorts, urban females have earlier menarche than rural (p < 0.05).

PMID- 25775916
TI  - Effectiveness of surgery in liver metastasis from colorectal cancer: experience
      and results of a continuous improvement process.
AB  - PURPOSE: The aim of this study was to estimate the effectiveness of surgery in
      liver metastasis from colorectal cancer. METHODS: We conducted a prospective and
      observational study of patients with colorectal liver metastasis operated on at
      the San Cecilio University Hospital of Granada from March 2003 until June 2013.
      The primary variables of the result were survival and morbidity before 30 days of
      the post-operative period. We also measured preoperative and surgical variables.
      RESULTS: A total of 147 patients with liver metastasis of colorectal origin
      underwent surgical removal during the period of study, 38 of whom had repeat
      surgery. 34 had a second resection, 3 had a third one and one only patient had a
      fourth one, for a total of 185 registered operations. The global 5-year survival
      rate was 38 and 17 % after 10 years. There were 115 patients who had neither
      radiofrequency nor exploratory laparotomy, 38 % of them survived over 60 months.
      The average disease-free time was 23.6 months +/- 47.3, with significant
      differences observed between types of procedures. Patients that were operated on
      just once (n = 25) had a five-year actuarial survival rate of 35 %, a morbidity
      rate of 24 % and a mortality rate of 0.6 % (1 patient only). The average hospital
      stay was 13.8 days and the disease-free time was 15.8 months. CONCLUSION: The
      results obtained in our surgical unit in terms of morbidity, mortality and five
      year actuarial survival rates are comparable to those of other units at large
      institutions, which are currently considered the standards of quality.

PMID- 25775917
TI  - Correlation between down-expression of miR-431 and clinicopathological
      significance in HCC tissues.
AB  - BACKGROUND AND AIMS: Researches have shown that miRNAs have been proposed as
      novel diagnostic biomarkers for classification and prognostic stratification of
      HCC. However, whether or not miR-431 contributes to the progression of HCC
      remains unknown. Therefore, we aimed to investigate the clinicopathological
      significance of miR-431 in HCC. METHODS: MiR-431 expression in 95 HCC cases and
      corresponding adjacent non-cancerous tissues was evaluated by quantitative
      reverse transcription polymerase chain reaction (qRT-PCR). Furthermore,
      statistical analysis was performed to identify the correlations between
      expression of miR-431 and a variety of clinicopathological parameters and patient
      recurrence. The area under the receiver operating characteristic curve (AUC) was
      used to evaluate the accuracy of miR-431 as a biomarker for HCC diagnosis and
      prediction of disease deterioration. RESULTS: MiR-431 was markedly down-regulated
      in the HCC samples (1.1885 +/- 0.75867) compared with corresponding adjacent
      tumor tissues (1.7957 +/- 0.89333, P < 0.001). The AUC of low miR-431 expression
      to diagnose HCC was 0.668 (95 % CI 0.592-0.744, P < 0.001). MiR-431 down
      expression was correlated with multiple malignant characteristics, including
      lymph node metastasis (r = -0.455, P < 0.001), clinical TNM stage (r = -0.223, P
      = 0.030), MTDH (r = -0.292, P = 0.006), vaso-invasion (r = -0.204, P = 0.047),
      MVD (r = -0.281, P = 0.006) and HCV (r = 0.215, P = 0.037). Additionally, the
      recurrent time of lower miR-431 expression group was 56.602 +/- 3.914 months,
      much longer than that in the high expression group (50.009 +/- 2.731 months),
      however, no significant difference was noted (chi (2) = 0.005, P = 0.943).
      CONCLUSIONS: The down-expression of miR-431 is partially responsible for a series
      of clinicopathological features which may be tightly correlated with the
      progression of HCC. Thus, expression of miR-431 may be proposed as a new factor
      in association with the progression of HCC.

PMID- 25775919
TI  - Can we create ethnically diverse skeletal collection from donated bodies?
AB  - Understanding bone health is least invasively and most effectively done through
      studying skeletal remains that reflect the living populations who will benefit
      from the knowledge produced through research. Donated body collections that
      accurately represent modern populations are needed for osteological insights to
      be applied to clinical practices. However, even though the US is growing
      increasingly diverse, donated body collections still suffer from a lack of ethnic
      diversity. Most individuals who donate their whole-bodies after death are
      European-American. Reasons for a lack of ethnic diversity stem from past
      injustices and present religious norms. Increasing body donation among minorities
      in the US and abroad may be difficult. 

PMID- 25775918
TI  - Single fraction volumetric modulated arc radiosurgery of brain metastases.
AB  - PURPOSE: To show the clinical results of the treatment of brain metastases via
      radiosurgery using Volumetric Modulated Arc Therapy (VMAT). MATERIALS AND
      METHODS: 52 patients having lung (62 %), breast (17 %), colorectal (8 %) and
      other cancers (13 %) with one to three brain metastases were treated with 5 non
      coplanar VMAT arcs. The treatment dose varied from 12 to 20 Gy, administered in
      one single session. The volume of metastases ranged from 0.04 to 24.92 cc.
      Radiosurgery alone was used for 54 % of cases, while 19 % received whole brain
      radiotherapy due to relapse. Patients were classified according to the Disease
      specific graded prognostic assessment (DS-GPA) index and survival was assessed
      via the Kaplan-Meier model. RESULTS: The median survival time was 7.2 months from
      the date of radiosurgery. The Karnofsky and DS-GPA indices were the most
      significant with regard to survival. Patients with a Karnofsky performance status
      (KPS) over 70 had a longer survival time of 9.2 months, as opposed to those with
      a KPS below 70 of 3.5 months. No significant differences were found with regard
      to the type of cancer or the number of lesions. Local tumour control was achieved
      for 42 metastases (82 %), of which a complete response was achieved for 7
      lesions, a partial response for 21; 15 lesions were stabilized. Local progression
      was observed in 8 lesions (15 %). The median treatment time per patient was 29
      min. CONCLUSIONS: The VMAT technique proves to be safe and effective for treating
      brain metastases via radiosurgery.

PMID- 25775920
TI  - The Role of Regulatory Agencies and Intellectual Property: Part II.
AB  - Patent law and antitrust law have traditionally been areas of the law involving
      at least some inherent tension. Champions of antitrust argue that the patent
      "monopoly" must be strictly limited as an exception to the general legal
      principle that competition should be unfettered. Patent lawyers argue that
      patents are the result of an exercise of congressional authority, enshrined in
      the Constitution, reflecting the policy decision by the Founders that granting a
      limited exclusionary right was justified by the public benefits derived from full
      disclosure of the patented invention. In the modern era these competing values
      have played out in the context of so-called ANDA litigation, involving disputes
      between branded pharmaceutical companies and generic competitors. Settlement of
      such litigation has been identified by the Federal Trade Commission (FTC), and
      private parties encouraged by the FTC's position, as an antitrust violation, in
      large part because such settlements are viewed as frustrating the congressional
      purpose in promoting early generic competition. After almost a decade of fighting
      these battles in the federal courts, the Supreme Court addressed the issue
      directly. The result is that such settlements are not per se illegal but are also
      not protected by the presumption of patent validity for activities within the
      "scope of the patent." Rather, the court decided that these agreements should be
      assessed for antitrust liability under the "rule of reason" used in other
      antitrust contexts. 

PMID- 25775921
TI  - The Role of Regulatory Agencies and Intellectual Property: Part I.
AB  - The patent and regulatory regimes of different agencies of the federal government
      are not always in agreement, and although the concept of the "unified executive"
      holds that the executive branch speaks with one voice, that is not always the
      case.(1) Some agencies, like the Food and Drug Administration, tend toward
      cooperation with government patent policies, whereas others, notably the Federal
      Trade Commission, are often at odds with the Patent Office, the patent system, or
      both. These skirmishes, when they arise, eventually come before federal courts
      and ultimately the Supreme Court, where balancing the differing policy
      objectives, as well as the will of Congress as embodied in its statutes, is
      subject to the vagaries of the politics of how the issues are framed by the
      courts, and the judges' and justices' own predilections and prejudices. Examples
      of these situations were prevalent in 2013 and the circumstances surrounding them
      illustrative of the tensions inherent between the various federal agencies. 

PMID- 25775923
TI  - Accumulation of lipid in rat liver was induced by vitamin B6 deficiency and was
      ameliorated by supplemental phosphatidylcholine in the diet.
AB  - We investigated the efficacy of supplementing the diet with pteroylmonoglutamic
      acid (PGA), choline, or phosphatidylcholine (PC) in ameliorating the lipid
      accumulation in rat liver that is induced by vitamin B6 (B6) deficiency. In
      Experiment 1, male Wistar rats were fed a control, B6-deficient, or PGA-, choline
      , or PC-supplemented (10 mg, 4 g, and 6.3 g/kg of diet, respectively) B6
      deficient diet containing l-methionine at 9 g/kg of diet for 35 days. In
      Experiment 2, rats were fed a control, B6-deficient, or PC-supplemented (at 3.15,
      6.3, or 12.6 g PC/kg of diet) B6-deficient diet for 35 days. Choline or PC
      supplementation ameliorated liver lipid deposition and returned plasma lipids to
      normal. Judging from these results, it appeared that B6 deficiency decreased the
      synthesis of PC in the liver, thereby decreasing the secretion of very low
      density lipoproteins, and in consequence producing lipid accumulation in the
      liver and reductions of plasma lipids.

PMID- 25775925
TI  - The advantage of CT scans and 3D visualizations in the analysis of three child
      mummies from the Graeco-Roman Period.
AB  - Three child mummies from the Graeco-Roman Period (332 BCE - c. 395 CE) were
      examined using CT scans and 3D visualizations generated with Vitrea 2 and MIMICS
      graphic workstations with the aim of comparing the results with previous X-ray
      examinations performed by Dawson and Gray in 1968. Although the previous analyses
      reported that the children had been excerebrated and eviscerated, no evidence of
      incisions or breaches of the cranial cavity were found; 3D visualizations were
      generated showing the brain and the internal organs to be in situ. A larger
      number of skeletal post-mortem damages were identified, such as dislocation of
      mandible, ribs, and vertebrae, probably suffered at the time of embalming
      procedure. Different radio-opaque granular particles were observed throughout
      bodies (internally and externally) and could be explained as presence of natron,
      used as external desiccating agent by the embalmers, or as adipocerous
      alteration, a natural alteration of body fat. Age-at-death was estimated using
      the 3D visualization of the teeth, the state of fusion of the vertebrae and the
      presence of the secondary centers of the long bones: two mummies died at the age
      of 4 years +/- 12 months, the third one at the age of 6 years +/- 24 months.
      Hyperdontia or polydontia, a dental anomaly, could also be identified in one
      child using 3D visualizations of the teeth: two supernumerary teeth were found
      behind the maxillary permanent central incisors which had not been noticed in the
      Dawson and Gray's X-ray analysis. In conclusion, CT-scan investigations and
      especially 3D visualizations are important tools in the non-invasive analysis of
      the mummies and, in this case, provided revised and additional information
      compared to the only X-ray examination. 

PMID- 25775924
TI  - Characteristics of systemic hypertension in preterm children.
AB  - The prevalence of essential hypertension (EH) among preterm children is unknown.
      The authors evaluated consecutive children with a diagnosis of hypertension and
      prematurity (gestational age <37 weeks) in a tertiary pediatric hypertension
      clinic and identified 36 preterm hypertensive children. Among these preterm
      children, 23 were diagnosed in the neonatal intensive care unit (NICU; infantile)
      and 13 were diagnosed at an older age (childhood). When compared with patients
      with a childhood diagnosis, patients with an infantile diagnosis had a
      significantly lower gestational age, longer duration of hospitalization in the
      NICU, and a higher incidence of perinatal risk factors for hypertension. None
      with infantile diagnosis had EH, whereas 46% with childhood diagnosis had EH.
      Among premature children, systemic hypertension was either diagnosed in infancy
      or in childhood, with each age at diagnosis having unique risk factors and
      clinical course. Although 83% of preterm children had secondary hypertension, EH
      was diagnosed in 17% and was only seen in those diagnosed beyond infancy. 

PMID- 25775922
TI  - The perinatal microbiome and pregnancy: moving beyond the vaginal microbiome.
AB  - The human microbiome, the collective genome of the microbial community that is on
      and within us, has recently been mapped. The initial characterization of healthy
      subjects has provided investigators with a reference population for interrogating
      the microbiome in metabolic, intestinal, and reproductive health and disease
      states. Although it is known that bacteria can colonize the vagina, recent
      metagenomic studies have shown that the vaginal microbiome varies among
      reproductive age women. Similarly, the richness and diversity of intestinal
      microbiota also naturally fluctuate among gravidae in both human and nonhuman
      primates, as well as mice. Moreover, recent evidence suggests that microbiome
      niches in pregnancy are not limited to maternal body sites, as the placenta
      appears to harbor a low biomass microbiome that is presumptively established in
      early pregnancy and varies in association with a remote history of maternal
      antenatal infection as well as preterm birth. In this article, we will provide a
      brief overview on metagenomics science as a means to investigate the microbiome,
      observations pertaining to both variation and the presumptive potential role of a
      varied microbiome during pregnancy, and how future studies of the microbiome in
      pregnancy may lend to a better understanding of human biology, reproductive
      health, and parturition. 

PMID- 25775926
TI  - Timed intercourse for couples trying to conceive.
AB  - BACKGROUND: Fertility problems are very common, as subfertility affects about 10%
      to 15% of couples trying to conceive. There are many factors that may impact a
      couple's ability to conceive and one of these may be incorrect timing of
      intercourse. Conception is only possible from approximately five days before up
      to several hours after ovulation. Therefore, to be effective, intercourse must
      take place during this fertile period. 'Timed intercourse' is the practice of
      prospectively identifying ovulation and, thus, the fertile period to increase the
      likelihood of conception. Whilst timed intercourse may increase conception rates
      and reduce unnecessary intervention and costs, there may be associated adverse
      aspects including time consumption and stress. Ovulation prediction methods used
      for timing intercourse include urinary hormone measurement (luteinizing hormone
      (LH), estrogen), tracking basal body temperatures, cervical mucus investigation,
      calendar charting and ultrasonography. This review considered the evidence from
      randomised controlled trials for the use of timed intercourse on positive
      pregnancy outcomes. OBJECTIVES: To assess the benefits and risks of ovulation
      prediction methods for timing intercourse on conception in couples trying to
      conceive. SEARCH METHODS: We searched the following sources to identify relevant
      randomised controlled trials, the Menstrual Disorders and Subfertility Group
      Specialised Register, the Cochrane Central Register of Controlled Trials
      (CENTRAL), MEDLINE, EMBASE, PsycINFO, PubMed, LILACS, Web of Knowledge, the World
      Health Organization (WHO) Clinical Trials Register Platform and
      ClinicalTrials.gov. Furthermore, we manually searched the references of relevant
      articles. The search was not restricted by language or publication status. The
      last search was on 5 August 2014. SELECTION CRITERIA: We included randomised
      controlled trials (RCTs) comparing timed intercourse versus intercourse without
      ovulation prediction or comparing different methods of ovulation prediction for
      timing intercourse against each other in couples trying to conceive. DATA
      COLLECTION AND ANALYSIS: Two review authors independently assessed trial
      eligibility and risk of bias and extracted the data. The primary review outcomes
      were cumulative live birth and adverse events (such as quality of life,
      depression and stress). Secondary outcomes were clinical pregnancy, pregnancy
      (clinical or self-reported pregnancy, not yet confirmed by ultrasound) and time
      to conception. We combined data to calculate pooled risk ratios (RRs) and 95%
      confidence intervals (CIs). Statistical heterogeneity was assessed using the I(2)
      statistic. We assessed the overall quality of the evidence for the main
      comparisons using GRADE methods. MAIN RESULTS: We included five RCTs (2840 women
      or couples) comparing timed intercourse versus intercourse without ovulation
      prediction. Unfortunately one large study (n = 1453) reporting live birth and
      pregnancy had not published outcome data by randomised group and therefore could
      not be analysed. Consequently, four RCTs (n = 1387) were included in the meta
      analysis. The evidence was of low to very low quality. Main limitations for
      downgrading the evidence included imprecision, lack of reporting clinically
      relevant outcomes and the high risk of publication bias.One study reported live
      birth, but the sample size was too small to draw any relevant conclusions on the
      effect of timed intercourse (RR 0.75, 95% CI 0.16 to 3.41, 1 RCT, n = 17, very
      low quality).One study reported stress as an adverse event. There was no evidence
      of a difference in levels of stress (mean difference 1.98, 95 CI% -0.87 to 4.83,
      1 RCT, n = 77, low level evidence). No other studies reported adverse events.Two
      studies reported clinical pregnancy. There was no evidence of a difference in
      clinical pregnancy rates (RR 1.10, 95% CI 0.57 to 2.12, 2 RCTs, n = 177, I(2) =
      0%, low level evidence). This suggested that if the chance of a clinical
      pregnancy following intercourse without ovulation prediction is assumed to be
      16%, the chance of success following timed intercourse would be between 9% and
      33%.Four studies reported pregnancy rate (clinical or self-reported pregnancy).
      Timed intercourse was associated with higher pregnancy rates compared to
      intercourse without ovulation prediction in couples trying to conceive (RR 1.35,
      95% CI 1.06 to 1.71, 4 RCTs, n = 1387, I(2) = 0%, very low level evidence). This
      suggests that if the chance of a pregnancy following intercourse without
      ovulation prediction is assumed to be 13%, the chance following timed intercourse
      would be between 14% and 23%. Subgroup analysis by duration of subfertility
      showed no difference in effect between couples trying to conceive for < 12 months
      versus couples trying for >= 12 months. One trial reported time to conception
      data and showed no evidence of a difference in time to conception. AUTHORS'
      CONCLUSIONS: There are insufficient data available to draw conclusions on the
      effectiveness of timed intercourse for the outcomes of live birth, adverse events
      and clinical pregnancy. Timed intercourse may improve pregnancy rates (clinical
      or self-reported pregnancy, not yet confirmed by ultrasound) compared to
      intercourse without ovulation prediction. The quality of this evidence is low to
      very low and therefore findings should be regarded with caution. There is a high
      risk of publication bias, as one large study remains unpublished 8 years after
      recruitment finished. Further research is required, reporting clinically relevant
      outcomes (live birth, clinical pregnancy rates and adverse effects), to determine
      if timed intercourse is safe and effective in couples trying to conceive.

PMID- 25775927
TI  - Mutations in PTF1A are not a common cause for human VATER/VACTERL association or
      neural tube defects mirroring Danforth's short tail mouse.
AB  - Danforth's short tail (Sd) mutant mice exhibit defects of the neural tube and
      other abnormalities, which are similar to the human vertebral anomalies, anal
      atresia, cardiac defects, tracheosophageal fistula and/or esophageal atresia,
      renal and radial abnormalities, and limb defects (VATER/VACTERL) association,
      including defects of the hindgut. Sd has been shown to underlie ectopic gene
      expression of murine Ptf1a, which encodes pancreas-specific transcription factor
      1A, due to the insertion of a retrotansposon in its 5' regulatory domain. In
      order to investigate the possible involvement of this gene in human VATER/VACTERL
      association and human neural tube defects (NTDs), a sequence analysis was
      performed. DNA samples from 103 patients with VATER/VACTERL and VATER/VACTERL
      like association, all presenting with anorectal malformations, and 72 fetuses
      with NTDs, where termination of pregnancy had been performed, were included in
      the current study. The complete PTF1A coding region, splice sites and 1.5 kb of
      the 5' flanking promotor region was sequenced. However, no pathogenic alterations
      were detected. The results of the present study do not support the hypothesis
      that high penetrant mutations in these regions of PTF1A are involved in the
      development of human VATER/VACTERL association or NTDs, although rare mutations
      may be detectable in larger patient samples.

PMID- 25775928
TI  - Breaking bad news is a teachable skill in pediatric residents: A feasibility
      study of an educational intervention.
AB  - OBJECTIVE: Patients and physicians identify communication of bad news as a skill
      in need of improvement. Our objectives were to measure change in performance of
      first-year pediatric residents in the delivery of bad news after an educational
      intervention and to measure if changes in performance were sustained over time.
      METHODS: Communication skills of 29 residents were assessed via videotaped
      standardized patient (SP) encounters at 3 time points: baseline, immediately post
      intervention, and 3 months post-intervention. Educational intervention used was
      the previously published "GRIEV_ING Death Notification Protocol." RESULTS: The
      intraclass correlation coefficient demonstrated substantial inter-rater agreement
      with the assessment tool. Performance scores significantly improved from baseline
      to immediate post-intervention. Performance at 3 months post-intervention showed
      no change in two subscales and small improvement in one subscale. CONCLUSIONS: We
      concluded that breaking bad news is a complex and teachable skill that can be
      developed in pediatric residents. Improvement was sustained over time, indicating
      the utility of this educational intervention. PRACTICE IMPLICATIONS: This study
      brings attention to the need for improved communication training, and the
      feasibility of an education intervention in a large training program. Further
      work in development of comprehensive communication curricula is necessary in
      pediatric graduate medical education programs.

PMID- 25775929
TI  - Isothiazolinones: sensitizers not to miss in children.
AB  - Isothiazolinone is known to be a sensitizer and a frequent cause of contact
      dermatitis in adults. Cases of contact dermatitis have also recently been
      reported in children. Derivatives of isothiazolinone, such as
      methylisothiazolinone (MI) and methylchloroisothiazolinone (MCI), are commonly
      used in the care products of babies and children. This allergen should not be
      missed. 

PMID- 25775930
TI  - Introgressive hybridization: brown bears as vectors for polar bear alleles.
AB  - The dynamics and consequences of introgression can inform about numerous
      evolutionary processes. Biologists have therefore long been interested in
      hybridization. One challenge, however, lies in the identification of nonadmixed
      genotypes that can serve as a baseline for accurate quantification of admixture.
      In this issue of Molecular Ecology, Cahill et al. (2015) analyse a genomic data
      set of 28 polar bears, eight brown bears and one American black bear. Polar bear
      alleles are found to be introgressed into brown bears not only near a previously
      identified admixture zone on the Alaskan Admiralty, Baranof and Chichagof (ABC)
      Islands, but also far into the North American mainland. Elegantly contrasting
      admixture levels at autosomal and X chromosomal markers, Cahill and colleagues
      infer that male-biased dispersal has spread these introgressed alleles away from
      the Late Pleistocene contact zone. Compared to a previous study on the ABC Island
      population in which an Alaskan brown bear served as a putatively admixture-free
      reference, Cahill et al. (2015) utilize a newly sequenced Swedish brown bear as
      admixture baseline. This approach reveals that brown bears have been impacted by
      introgression from polar bears to a larger extent (up to 8.8% of their genome),
      than previously known, including the bear that had previously served as admixture
      baseline. No evidence for introgression of brown bear into polar bear is found,
      which the authors argue could be a consequence of selection. Besides adding new
      exciting pieces to the puzzle of polar/brown bear evolutionary history, the study
      by Cahill and colleagues highlights that wildlife genomics is moving from
      analysing single genomes towards a landscape genomics approach. 

PMID- 25775931
TI  - Use of GRADE for assessment of evidence about prognosis: rating confidence in
      estimates of event rates in broad categories of patients.

PMID- 25775932
TI  - Making the case for investment in public health: experiences of Directors of
      Public Health in English local government.
AB  - BACKGROUND: Amid local government budget cuts, there is concern that the ring
      fenced public health grant is being appropriated, and Directors of Public Health
      (DsPH) find it difficult to make the case for investment in public health
      activity. This paper describes what DsPH are making the case for, the components
      of their case and how they present the case for public health. METHODS: Thirteen
      semi-structured telephone interviews and a group discussion were carried out with
      DsPH (November 2013 to May 2014) in the Southern region of England. RESULTS: DsPH
      make the case for control of the public health grant and investing in action on
      wider determinants of health. The cases they present incorporate arguments about
      need, solutions and their effectiveness, health outcomes, cost and economic
      impact but also normative, political arguments. Many types of evidence were used
      to substantiate the cases; evidence was carefully framed to be accessible and
      persuasive. CONCLUSIONS: DsPH are responding to a new environment; economic
      arguments and evidence of impact are key components of the case for public
      health, although multiple factors influence local government (LG) decisions
      around health improvement. Further evidence of economic impact would be helpful
      in making the case for public health in LG.

PMID- 25775933
TI  - Using Google Glass to solve communication and surgical education challenges in
      the operating room.

PMID- 25775934
TI  - Ankyrin domain of myosin 16 influences motor function and decreases protein
      phosphatase catalytic activity.
AB  - The unconventional myosin 16 (Myo16), which may have a role in regulation of cell
      cycle and cell proliferation, can be found in both the nucleus and the cytoplasm.
      It has a unique, eight ankyrin repeat containing pre-motor domain, the so-called
      ankyrin domain (My16Ank). Ankyrin repeats are present in several other proteins,
      e.g., in the regulatory subunit (MYPT1) of the myosin phosphatase holoenzyme,
      which binds to the protein phosphatase-1 catalytic subunit (PP1c). My16Ank shows
      sequence similarity to MYPT1. In this work, the interactions of recombinant and
      isolated My16Ank were examined in vitro. To test the effects of My16Ank on myosin
      motor function, we used skeletal muscle myosin or nonmuscle myosin 2B. The
      results showed that My16Ank bound to skeletal muscle myosin (K D ~ 2.4 uM) and
      the actin-activated ATPase activity of heavy meromyosin (HMM) was increased in
      the presence of My16Ank, suggesting that the ankyrin domain can modulate myosin
      motor activity. My16Ank showed no direct interaction with either globular or
      filamentous actin. We found, using a surface plasmon resonance-based binding
      technique, that My16Ank bound to PP1calpha (K D ~ 540 nM) and also to PP1cdelta
      (K D ~ 600 nM) and decreased its phosphatase activity towards the phosphorylated
      myosin regulatory light chain. Our results suggest that one function of the
      ankyrin domain is probably to regulate the function of Myo16. It may influence
      the motor activity, and in complex with the PP1c isoforms, it can play an
      important role in the targeted dephosphorylation of certain, as yet unidentified,
      intracellular proteins.

PMID- 25775935
TI  - Homeopathy is not an effective treatment for any health condition, report
      concludes.

PMID- 25775936
TI  - Temperature dependence of exciton diffusion in a small-molecule organic
      semiconductor processed with and without additive.
AB  - The temperature dependence of exciton diffusion in a small-molecule organic
      semiconductor processed with and without additive is investigated. As-cast and
      1,8-diiodooctane-processed films yield exciton diffusion lengths of 6.8 and 4.9
      nm, respectively. Using a Monte Carlo simulation, it is shown that processing
      with 1,8-diiodooctane increases the excitonic trap density, which directly
      reduces the exciton diffusion length. 

PMID- 25775937
TI  - An adaptive MR-CT registration method for MRI-guided prostate cancer
      radiotherapy.
AB  - Magnetic Resonance images (MRI) have superior soft tissue contrast compared with
      CT images. Therefore, MRI might be a better imaging modality to differentiate the
      prostate from surrounding normal organs. Methods to accurately register MRI to
      simulation CT images are essential, as we transition the use of MRI into the
      routine clinic setting. In this study, we present a finite element method (FEM)
      to improve the performance of a commercially available, B-spline-based
      registration algorithm in the prostate region. Specifically, prostate contours
      were delineated independently on ten MRI and CT images using the Eclipse
      treatment planning system. Each pair of MRI and CT images was registered with the
      B-spline-based algorithm implemented in the VelocityAI system. A bounding box
      that contains the prostate volume in the CT image was selected and partitioned
      into a tetrahedral mesh. An adaptive finite element method was then developed to
      adjust the displacement vector fields (DVFs) of the B-spline-based registrations
      within the box. The B-spline and FEM-based registrations were evaluated based on
      the variations of prostate volume and tumor centroid, the unbalanced energy of
      the generated DVFs, and the clarity of the reconstructed anatomical structures.
      The results showed that the volumes of the prostate contours warped with the B
      spline-based DVFs changed 10.2% on average, relative to the volumes of the
      prostate contours on the original MR images. This discrepancy was reduced to 1.5%
      for the FEM-based DVFs. The average unbalanced energy was 2.65 and 0.38 mJ cm(
      3), and the prostate centroid deviation was 0.37 and 0.28 cm, for the B-spline
      and FEM-based registrations, respectively. Different from the B-spline-warped MR
      images, the FEM-warped MR images have clear boundaries between prostates and
      bladders, and their internal prostatic structures are consistent with those of
      the original MR images. In summary, the developed adaptive FEM method preserves
      the prostate volume during the transformation between the MR and CT images and
      improves the accuracy of the B-spline registrations in the prostate region. The
      approach will be valuable for the development of high-quality MRI-guided
      radiation therapy. 

PMID- 25775938
TI  - Impact of metagenomic DNA extraction procedures on the identifiable endophytic
      bacterial diversity in Sorghum bicolor (L. Moench).
AB  - Culture-independent studies rely on the quantity and quality of the extracted
      environmental metagenomic DNA (mDNA). To fully access the plant tissue
      microbiome, the extracted plant mDNA should allow optimal PCR applications and
      the genetic content must be representative of the total microbial diversity. In
      this study, we evaluated the endophytic bacterial diversity retrieved using
      different mDNA extraction procedures. Metagenomic DNA from sorghum (Sorghum
      bicolor L. Moench) stem and root tissues were extracted using two classical DNA
      extraction protocols (CTAB- and SDS-based) and five commercial kits. The mDNA
      yields and quality as well as the reproducibility were compared. 16S rRNA gene
      terminal restriction fragment length polymorphism (t-RFLP) was used to assess the
      impact on endophytic bacterial community structures observed. Generally, the
      classical protocols obtained high mDNA yields from sorghum tissues; however, they
      were less reproducible than the commercial kits. Commercial kits retrieved higher
      quality mDNA, but with lower endophytic bacterial diversities compared to
      classical protocols. The SDS-based protocol enabled access to the highest sorghum
      endophytic diversities. Therefore, "SDS-extracted" sorghum root and stem
      microbiome diversities were analysed via 454 pyrosequencing, and this revealed
      that the two tissues harbour significantly different endophytic communities.
      Nevertheless, both communities are dominated by agriculturally important genera
      such as Microbacterium, Agrobacterium, Sphingobacterium, Herbaspirillum, Erwinia,
      Pseudomonas and Stenotrophomonas; which have previously been shown to play a role
      in plant growth promotion. This study shows that DNA extraction protocols
      introduce biases in culture-independent studies of environmental microbial
      communities by influencing the mDNA quality, which impacts the microbial
      diversity analyses and evaluation. Using the broad-spectrum SDS-based DNA
      extraction protocol allows the recovery of the most diverse endophytic
      communities associated with sorghum tissues and, as such, establishes a reliable
      basis for future study of endophytic communities. 

PMID- 25775939
TI  - Combined Fibroadenoma and Tubular Adenoma of the Breast: Rare Presentation that
      Confirms Common Histogenesis.

PMID- 25775940
TI  - An IDB-containing low molecular weight short peptide as an efficient DNA cleavage
      reagent.
AB  - Artificial nucleases have attracted significant interest due to their abilities
      in accelerating DNA cleavage, which results in the possibility of genome
      manipulation. However, compared with natural nucleases, the currently available
      artificial nucleases have low cleavage efficiency, especially metal-free
      artificial nucleases. Thus, it is still a challenge to develop highly efficient
      metal-free artificial nucleases via a non-oxidative pathway. We here designed and
      prepared a group of rigid bis-amine-grafted PASP conjugates (PASP-IDB), and
      investigated their abilities to induce DNA double-strand cleavage. The detailed
      assays showed that in the absence of metal ions, these short peptide conjugates
      can effectively break the phosphodiester linkage at a relatively low
      concentration and under physiological conditions through a hydrolytic process,
      giving the 10(7)-fold rate acceleration over uncatalyzed double-strand DNA. The
      probable mechanism verified by control experiments revealed that IDBs and free
      carboxyl groups in PASP synergically catalyzed DNA cleavage. In addition, the
      effects of degrees of substitution on the cleavage activity were studied, and the
      results indicated the existence of minimum building blocks of PASP-IDB for
      efficient DNA cleavage. The results of our study have implications on the design
      of short peptide-based molecules as new artificial nucleases and may provide a
      strategy for developing safe and efficient metal-free DNA cleavage reagents. 

PMID- 25775941
TI  - Faecal egg counts and expulsion dynamics of the whipworm, Trichuris trichiura
      following self-infection.
AB  - More than 400 million humans are estimated to be infected with the intestinal
      helminth parasite, Trichuris trichiura. The infection is chronic in nature and
      high-intensity infection can lead to colitis, anaemia, Trichuris Dysentery
      Syndrome and reduced cognitive performance. Single doses of 400 mg albendazole or
      500 mg mebendazole (MBZ) are used in mass drug administration programmes, but
      this has been shown to be insufficient. In this study, worm expulsion dynamics
      are described after MBZ treatment, given as a multi-dose and single-dose
      treatment in two separate T. trichiura self-infection studies. Worm expulsion
      dynamics post-treatment showed a similar pattern regardless of the dose regime,
      with the first worms observed on day 2 and the last worms expelled on days 9 and
      13 post-treatment. Establishment of a chronic infection was observed following
      the inefficient single-dose treatment. The prepatent period was 13-16 weeks in
      both studies and worms were found to have a lifespan of at least 1 year and 10
      months. These self-infection studies provide key information on the chronicity of
      T. trichiura infections, expulsion dynamics after anthelmintic treatment and the
      prepatent period, as well as the fecundity of female worms, which was around
      18,000 eggs/female per day. 

PMID- 25775942
TI  - DFT/TDDFT study on the photodissociation mechanism of the original monascus red
      and orange pigments.
AB  - The weak photostability has to some extent restricted the wide utilization of
      monascus pigments in food industries, and their photobleaching mechanism is
      unclear yet. Density functional theory and time-dependent density functional
      theory at B3LYP/6-311+G(d,p) level have been performed to optimize the geometries
      of ground states, single and triplet excited-states of the original monascus red
      and orange pigments, the possible photodissociation mechanism of which is
      analyzed according to the calculated data. It is the break of the chromophores,
      conjugated pi bonds which has induced their decoloration. The photodissociation
      of these pigments involves three steps, excitation of the large conjugated pi
      system, water addition to the singlet or triplet excited-state, and Norrish type
      I photochemical cleavage reactions of the side chains. The former two steps are
      much more important steps which have led to the destruction of the chromophores
      and the fading of the four original monascus red and orange pigments. According
      to the photobleaching mechanism obtained, one could find some solutions to
      enhance the photostability of these monascus colorants during the food processing
      process and extend the shelf life of the foods added with monascus pigments. 

PMID- 25775943
TI  - Synthesis, spectral, thermal and antimicrobial studies of transition metal
      complexes of 14-membered tetraaza[N4] macrocyclic ligand.
AB  - A series of metal complexes of Mn(II), Co(II), Ni(II), Cu(II), have been
      synthesized with newly synthesized biologically active macrocyclic ligand. The
      ligand was synthesized by condensation of beta-diketone 1-(4-chlorophenyl)-3-(2
      hydroxyphenyl)propane-1,3-dione and o-phenylene diamine. All the complexes were
      characterized by elemental analysis, molar conductivity, magnetic susceptibility,
      thermal analysis, X-ray diffraction, IR, (1)H-NMR, UV-Vis spectroscopy and mass
      spectroscopy. From the analytical data, stoichiometry of the complexes was found
      to be 1:2 (metal:ligand). Thermal behavior (TG/DTA) and kinetic parameters
      suggest more ordered activated state in complex formation. All the complexes are
      of high spin type and six coordinated. On the basis of IR, electronic spectral
      studies and magnetic behavior, an octahedral geometry has been assigned to these
      complexes. The antibacterial and antifungal activities of the ligand and its
      metal complexes, has been screened in vitro against Staphylococcus aureus,
      Escherichia coli and Aspergillus niger, Trichoderma respectively. 

PMID- 25775944
TI  - Photoluminescence properties of a novel red emitting Ba10F2(PO 4)6:Eu3+ phosphor.
AB  - A novel red-emitting phosphor Ba10F2(PO4)6:Eu(3+) is synthesized by a high
      temperature solid-state reaction. X-ray powder diffraction (XRD) analysis
      confirms the phase formation of Ba10F2(PO4)6:Eu(3+) materials. The
      photoluminescence excitation (PLE) and emission (PL) spectra, the concentration
      dependence of the emission intensity, decay curves and Commission International
      de I'Eclairage (CIE) of the phosphors are investigated. It is observed that
      Ba10F2(PO4)6:Eu(3+) phosphors exhibit two dominating bands situated at 591 and
      616 nm, originating from the (5)D0->(7)F1 and (5)D0->(7)F2 transition of the
      Eu(3+) ion, respectively. The decay time is also determined for various
      concentrations of Eu(3+) in Ba10F2(PO4)6:Eu(3+). Crystal lattice, PL spectra and
      decay time analysis indicate there exist two isolated Eu(3+) crystallography
      sites in Ba10F2(PO4)6. The calculated color coordinates lie in the red region.
      Therefore, Ba10F2(PO4)6:Eu(3+) phosphors may be good candidates for red
      components in near-UV (NUV) white LEDs.

PMID- 25775945
TI  - Partitioning of organophosphorus pesticides into phosphatidylcholine small
      unilamellar vesicles studied by second-derivative spectrophotometry.
AB  - In order to quantitatively examine the lipophilicity of the widely used
      organophosphorus pesticides (OPs) chlorfenvinphos (CFVP), chlorpyrifos-methyl
      (CPFM), diazinon (DZN), fenitrothion (FNT), fenthion (FT), isofenphos (IFP),
      profenofos (PFF) and pyraclofos (PCF), their partition coefficient (Kp) values
      between phosphatidylcholine (PC) small unilamellar vesicles (SUVs) and water
      (liposome-water system) were determined by second-derivative spectrophotometry.
      The second-derivative spectra of these OPs in the presence of PC SUV showed a
      bathochromic shift according to the increase in PC concentration and distinct
      derivative isosbestic points, demonstrating the complete elimination of the
      residual background signal effects that were observed in the absorption spectra.
      The Kp values were calculated from the second-derivative intensity change induced
      by addition of PC SUV and obtained with a good precision of R.S.D. below 10%. The
      Kp values were in the order of CPFM>FT>PFF>PCF>IFP>CFVP>FNT?DZN and did not show
      a linear correlation relationship with the reported partition coefficients
      obtained using an n-octanol-water system (R(2)=0.530). Also, the results
      quantitatively clarified the effect of chemical-group substitution in OPs on
      their lipophilicity. Since the partition coefficient for the liposome-water
      system is more effective for modeling the quantitative structure-activity
      relationship than that for the n-octanol-water system, the obtained results are
      toxicologically important for estimating the accumulation of these OPs in human
      cell membranes. 

PMID- 25775946
TI  - An experimental re-examination of the inferential confusion hypothesis of
      obsessive-compulsive doubt.
AB  - BACKGROUND AND OBJECTIVES: The inferential confusion hypothesis postulates that
      obsessive doubt is perpetuated by a subjective form of reasoning characterized
      primarily by a distrust of reality and an overreliance on imagined possibilities.
      However, experimental evidence for this hypothesis may be compromised by a
      potential confound between type of information (reality vs. possibility) and its
      valence (danger vs. safety). In the present study we aimed to untangle this
      potential confound. METHODS: Forty OCD and 40 non-clinical participants underwent
      two versions of the Inferential Processes Task (Aardema, F., et al. (2009). The
      quantification of doubt in obsessive-compulsive disorder. International Journal
      of Cognitive Therapy, 2, 188-205). In the original version, the reality-based
      information is congruent with the safety hypothesis, whereas the possibility
      based information is congruent with the danger hypothesis. In the modified
      version incorporated in the present study, the reality-based information is
      congruent with the danger hypothesis, whereas the possibility-based information
      is congruent with the safety hypothesis. RESULTS: Our findings did not support
      the inferential confusion hypothesis: both OCD and control participants changed
      their estimations of the probability of unwanted events based on the type of
      information they received (whether it conveyed danger or safety) regardless of
      whether it was framed as reality or possibility. LIMITATIONS: The design of the
      present study does not lend itself to examining alternative explanations for the
      persistence of doubt in OCD. CONCLUSIONS: The hypothesized inferential confusion
      in OCD requires further validation. It is particularly important to demonstrate
      that findings do not reflect a prudential reasoning strategy.

PMID- 25775947
TI  - Decreasing self-reported cognitive biases and increasing clinical insight through
      meta-cognitive training in patients with chronic schizophrenia.
AB  - BACKGROUND AND OBJECTIVES: The aim of this study was to assess the impact of meta
      cognitive training (MCT) on cognitive biases, symptoms, clinical insight, and
      general functioning among low-level functioning persons diagnosed with chronic
      schizophrenia who were attending a daily Community Social Support Group Program;
      we compared the treatment-as-usual (TAU) condition with the MCT + TAU condition.
      METHODS: Forty-four patients diagnosed with chronic schizophrenia were allocated
      to either the MCT + treatment-as-usual condition or the treatment-as-usual (TAU)
      condition. Delusion and hallucination severity, cognitive biases, clinical
      insight, and global functioning were assessed pre- and post-treatment (clinical
      trial NCT02187692). RESULTS: No significant changes were found in symptom
      severity as measured with the PSYRATS. Conversely, a medium to large effect size
      was observed for delusional ideation changes when assessed by the self-report
      measure (Paranoia Checklist). MCT was found to ameliorate cognitive biases as
      measured by the self-report scale at large effect size, however, no changes in
      jumping to conclusions (the Fish Task) and theory of mind deficits ("Reading the
      Mind in the Eyes" Test) were found in the behavioral tasks. MCT increased insight
      at large effect size. No changes in global functioning were found between the two
      conditions. LIMITATIONS: Low intensity intervention. No follow-up assessment was
      provided. Only PSYRATS was assessed blind to patient allocation. CONCLUSIONS: MCT
      has a beneficial effect on low-functioning chronic schizophrenic patients in
      ameliorating cognitive biases and increasing clinical insight.

PMID- 25775948
TI  - Significance of Trask protein interactions in brain metastatic cohorts of lung
      cancers.
AB  - A class of adhesion protein that occurs in the membrane with both extracellular
      and intracellular domain and play vital role in maintaining multicellularity is
      TRASK, also called CUB-domain containing protein1, CD318 (CDCP1). Specifically,
      in the current study, documented aggressive grades of lung cancers and distant
      metastatic tissues were examined for protein interactions of Trask and compared
      with lung cancer variants in situ. The intracellular domain of Trask has the
      ability to undergo tyrosine phosphorylation and thereafter undergo increased
      genomic expression, as well as interact with cytoskeletal proteins in the cell
      periphery and other local signal transduction machinery to induce invadopodia
      formation and distant metastasis. We incorporated proximity ligation assay to
      examine protein interactions of Trask in metastatic lung cancer tissues and
      compare with advanced and low-grade lung cancers restricted to the primary site
      of origins. Here, we provide direct evidence that activated Trask, which is a
      phosphorylated form, binds with cytoskeletal proteins actin and spectrin. These
      interactions were not seen in locally growing lung cancer and cancer in situ.
      These interactions may be responsible for invadopodia formation and breaking free
      from a multicellular environment. Functional studies demonstrated interaction
      between Trask and the STOCs Orai1 and Stim1. Calcium release from internal stores
      was highest in metastatic lung cancers, suggesting this mechanism as an initial
      stimulus for the cells to respond chaotically to external growth factor
      stimulation, especially in aggressive metastatic variants of lung cancers.
      Recently, inhibitors of STOCs have been identified, and preclinical evidence may
      be obtained whether these drugs may be of benefit in preventing the deadly
      consequences of lung cancer.

PMID- 25775949
TI  - Synthetic miRNA sponges driven by mutant hTERT promoter selectively inhibit the
      progression of bladder cancer.
AB  - The mutant promoter of human telomerase reverse transcriptase (hTERT) shows high
      transcriptional activity in bladder cancer cells. Some up-regulated microRNAs
      (miRNAs) are reported as oncogenic factors in bladder cancer. Previous studies
      report that miRNAs can be inhibited by base-pairing interactions. The purpose of
      this study is to construct a synthetic device driven by mutant hTERT promoter to
      suppress four up-regulated miRNAs and to verify its effects on phenotypes of
      bladder cancer cells and human normal cells. Tandem bulged miRNA binding sites
      targeting oncogenic miRNAs were inserted into the 3' untranslated region (3' UTR)
      of mutant hTERT promoter-driven Renilla luciferase gene to construct a synthetic
      tumor-specific device, miRNA sponges. A negative control was generated by using
      tandem repeated sequences without targeting any known miRNA. Bladder cancer cells
      (T24, 5637, UM-UC-3) and human fiber cells (HFC) were transfected with devices.
      Various functional assays were used to detect the effects of this device. The
      activity of the mutant hTERT promoter detected by luciferase assay was about
      three times as large as the wild-type hTERT promoter in bladder cancer cells,
      while it could not be measured in HFC. Other assays indicated that the synthetic
      device can significantly inhibit cell growth, decrease motility, and induce
      apoptosis in bladder cancer cells but not in HFC. A synthetic biology platform is
      employed to construct tumor-specific miRNA sponges that can be used to target
      oncogenic miRNAs to inhibit the progression of bladder cancer cells without
      affecting normal cells. 

PMID- 25775950
TI  - Association between SNPs in Serpin gene family and risk of esophageal squamous
      cell carcinoma.
AB  - Esophageal squamous cell carcinoma (ESCC) is one of the most aggressive cancers
      in the world. Epidemiological survey studies have verified that the development
      of ESCC relates to a complex interactive process between multiple genetic
      susceptibilities and environmental exposure. Serpins are a broadly distributed
      family of protease inhibitors and have been recognized as tumor suppressors in
      multiple cancer types. While previous studies have reported that Serpin
      polymorphisms are associated with tumorigenesis, the genetic and functional
      single nucleotide polymorphisms (SNP) in these genes appear to be complex and
      remain to be elucidated. In this study, a total of 500 ESCC cases and 500 matched
      controls in a Southwest China population were evaluated for six SNPs in the exons
      of three Serpin genes (SerpinB5, SerpinB2, and SerpinE1). Among the six SNPs, the
      C allele of rs2289519 and rs2289520 in SerpinB5 showed decreased risk of ESCC and
      the variants might interact with smoking status. Haplotype analysis showed that
      the T-G haplotype (corresponding to rs2289519-rs2289520) increased the risk of
      ESCC, while the C-C haplotype decreased the risk. We also found that SerpinB5
      gene mRNA expression was significantly downregulated in ESCC cell lines and
      patient specimen while there is no change in protein structure with different
      haplotypes. Our results demonstrated that the expression of SerpinB5 was
      downregulated in ESCC, and the positive SNPs might be associated with a risk of
      ESCC development.

PMID- 25775951
TI  - Stromal cells of endometrial carcinoma promotes proliferation of epithelial cells
      through the HGF/c-Met/Akt signaling pathway.
AB  - Tumor microenvironment participates in the endometrial carcinoma pathogenesis.
      This study focuses on the interaction between endometrial cancer stromal cells
      and epithelial cells from normal endometrium tissue using in vitro transwell
      coculture system and in vivo xenograft model. We demonstrate that cancer
      interstitial (CI) cells stimulate normal epithelial (NE) cell proliferation.
      Tumor xenograft model confirmed the pro-proliferative effect of CI cells on
      epithelial cell growth. Tumor suppressor PTEN was reduced, and oncogene K-ras was
      increased in epithelial cells cocultured with CI cells. Moreover, we observed
      increased expression of hepatocyte growth factor (HGF) in CI cells and tumor
      xenografts derived from the coculturing system. Higher HGF secretion activated
      Akt signaling pathway, which was reversed by HGF receptor inhibitor (crizotinib).
      These results demonstrate that endometrial carcinoma stromal cells stimulate
      epithelial cell proliferation via the HGF/c-Met/Akt signaling pathway.

PMID- 25775952
TI  - Structural conservation among the rhodopsin-like and other G protein-coupled
      receptors.
AB  - Intramolecular remote coupling within the polypeptide backbones of membrane
      proteins is difficult to analyze owing to the limited structural information
      available at the atomic level. Nonetheless, recent progress in the
      crystallographic study of G protein-coupled receptors (GPCRs) has provided an
      unprecedented opportunity for understanding the sophisticated architecture of
      heptahelical transmembrane (7TM) bundles. These 7TM bundles can respond to a wide
      range of extracellular stimuli while retaining the common function of binding
      trimeric G proteins. Here we have systematically analyzed select sets of inactive
      like 7TM bundles to highlight the structural conservation of the receptors, in
      terms of intramolecular Calpha-Calpha distances. Distances with the highest
      scores were found to be dominated by the intrahelical distances of helix III,
      regardless of the choice of bundles in the set, indicating that the intracellular
      half of this helix is highly conserved. Unexpectedly, the distances between the
      cytoplasmic side of helix I and the extracellular region of helix VI provided the
      largest contribution to the high score populations among the interhelical pairs
      in most of the selected sets, including class B, C and frizzled receptors. These
      findings are expected to be valuable in further studies of GPCRs with unknown
      structure and of other protein families. 

PMID- 25775954
TI  - A high performance graphene/few-layer InSe photo-detector.
AB  - We fabricated a graphene/few-layer InSe heterostructure photo-detector and solved
      a recurrent materials problem concerning degradation of ultra-thin atomic layers
      in air. This heterostructure has a largely enhanced performance explained by its
      fundamentally different mode of functioning with respect to the corresponding
      device without graphene. 

PMID- 25775953
TI  - Improved cytodiagnostics and quality of patient care through double reading of
      selected cases by an expert cytopathologist.
AB  - Double reading may be a valuable tool for improving the quality of patient care
      by restoring diagnostic errors before final sign-out, but standard double reading
      would significantly increase costs of pathology. The aim of this study was to
      assess the added value of routine double reading of defined categories of
      clinical cytology specimens by specialized cytopathologists. Specialized
      cytopathologists routinely re-diagnosed blinded defined categories of clinical
      cytology specimens that had been signed out by routine pathologists from January
      2012 up to December 2013. Major and minor discordance rates between initial and
      expert diagnoses were determined, and both diagnoses were validated by comparison
      with same-site histological follow-up. Initial and expert diagnoses were
      concordant in 131/218 specimens (60.1 %). Major and minor discordances were
      present in 28 (12.8 %) and 59 (27.1 %) specimens, respectively. Pleural fluid,
      thyroid and urine specimens showed the highest major discordance rates (19.4,
      19.2 and 16.7 %, respectively). Histological follow-up (where possible) supported
      the expert diagnosis in 95.5 % of specimens. Our implemented double reading
      strategy of defined categories of cytology specimens showed major discordance in
      12.8 % of specimens. The expert diagnosis was supported in 95.5 % of discordant
      cases where histological follow-up was available. This indicates that this double
      reading strategy is worthwhile and contributes to better cytodiagnostics and
      quality of patient care, especially for suspicious pleural fluid, thyroid and
      urine specimens. Our results emphasize that cytopathology is a subspecialization
      of pathology and requires specialized cytopathologists.

PMID- 25775956
TI  - Foetal dilated cardiomyopathy with left ventricular thrombosis.
AB  - Serial foetal echocardiography showed the development of severe left ventricular
      systolic dysfunction and thrombosis in a previously healthy foetus. Normal
      cardiac findings in a mid-trimester foetus do not exclude subsequent dilated
      cardiomyopathy. 

PMID- 25775955
TI  - Overcoming practical challenges to conducting clinical research in the inpatient
      stroke rehabilitation setting.
AB  - BACKGROUND: There is a shortage of published empirical studies conducted in acute
      inpatient stroke rehabilitation, though such studies are greatly needed in order
      to shed light on the most efficacious inpatient stroke rehabilitation
      interventions. The inherent challenges of inpatient research may dissuade
      researchers from undertaking this important work. OBJECTIVE: This paper describes
      our institution's experience devising practical solutions to research barriers in
      this setting. METHOD: Through concentrated efforts to overcome research barriers,
      such as by cultivating collaborative relationships and capitalizing on
      unanticipated benefits, we successfully facilitated conduct of five simultaneous
      inpatient stroke studies. RESULTS: Tangible benefits realized include increased
      effectiveness of research participant identification and enrollment, novel
      collaborative projects, innovative clinical care initiatives, and enhanced
      emotional and practical support for patients and their families. We provide
      recommendations based on lessons learned during our experience, and discuss
      benefits of this collaboration for our research participants, clinical staff, and
      the research team.

PMID- 25775957
TI  - The significance of allergic contact urticaria to milk in children with cow's
      milk allergy.
AB  - BACKGROUND: Cow's milk allergy (CMA) is the most common food allergy in infancy.
      Food allergy is generally triggered through ingestion, but can also be triggered
      through skin contact. We investigated the incidence and the clinical significance
      of cow's milk protein (CMP)-induced contact urticaria in individuals with CMA
      with and without atopic dermatitis (AD). METHODS: A total of 157 children of whom
      133 were diagnosed with CMA were participated. The study was based on
      observational data gathered in the course of patient care, including a skin prick
      test and a 'finger test', in which cow's milk is applied on the cheek by a
      physician's finger to detect contact urticaria. RESULTS: Eighty nine of 133
      patients (66.9%) had IgE-mediated CMA. Forty of these 89 (44.9%) tested positive
      in the finger test. Family atopy was higher in those with positive contact
      urticaria [21/40 (52.5%) vs. 14/49 (28.5%), p = 0.029]. Patients with positive
      vs. negative CMP contact urticaria had higher incidence of multiple food
      allergies [20 of 40 (50%) vs. 7/49 (14.3%), p < 0.004]. IgE-mediated CMA patients
      with AD had statistically higher CMP allergic contact urticaria compared to
      patients without AD [71% (15/21) vs. 37% (25/68), p = 0.0064]. Children with non
      IgE milk allergy and healthy control group did not have contact urticaria to CMP.
      CONCLUSION: CMP contact urticaria exists only in patients with IgE-mediated CMA.
      A 'finger test' to CMP should be part of the evaluation of CMA patients, and
      positivity suggests the potential for multiple food allergies, especially to
      sesame and egg.

PMID- 25775967
TI  - A highly sensitive and class-specific fluorescence polarisation assay for
      sulphonamides based on dihydropteroate synthase.
AB  - We describe a fluorescence polarisation assay based on the use of dihydropteroate
      synthase (DHPS) and a fluorescence probe for multi-sulphonamide detection.
      Dihydropteridine pyrophosphate (DHPPP) was synthesised and acts as the first
      substrate for DHPS. Under optimised conditions, the half-maximal inhibitory
      concentrations (IC50) of the assay were less than 100 ng mL(-1) for at least 29
      sulphonamides and the time needed for the detection was less than 20 min. More
      importantly, the assay revealed quite uniform affinities for all of the
      individual sulphonamides tested, which has never before been achieved in an
      antibody-based assay.

PMID- 25775968
TI  - Portable smartphone quantitation of prostate specific antigen (PSA) in a
      fluoropolymer microfluidic device.
AB  - We present a new, power-free and flexible detection system named MCFphone for
      portable colorimetric and fluorescence quantitative sandwich immunoassay
      detection of prostate specific antigen (PSA). The MCFphone is composed by a
      smartphone integrated with a magnifying lens, a simple light source and a
      miniaturised immunoassay platform, the Microcapillary Film (MCF). The excellent
      transparency and flat geometry of fluoropolymer MCF allowed quantitation of PSA
      in the range 0.9 to 60 ng/ml with<7% precision in 13 min using enzymatic
      amplification and a chromogenic substrate. The lower limit of detection was
      further improved from 0.4 to 0.08 ng/ml in whole blood samples with the use of a
      fluorescence substrate. The MCFphone has shown capable of performing rapid (13 to
      22 min total assay time) colorimetric quantitative and highly sensitive
      fluorescence tests with good %Recovery, which represents a major step in the
      integration of a new generation of inexpensive and portable microfluidic devices
      with commercial immunoassay reagents and off-the-shelf smartphone technology.

PMID- 25775969
TI  - Label-free fluorescence dual-amplified detection of adenosine based on
      exonuclease III-assisted DNA cycling and hybridization chain reaction.
AB  - In this work, we constructed a label-free and dual-amplified fluorescence
      aptasensor for sensitive analysis of adenosine based on exonuclease III (Exo III)
      assisted DNA cycling and hybridization chain reaction (HCR). Firstly, we
      fabricated a trifunctional probe that consisting of the catalytic strand, the
      aptamer sequence and a streptavidin-magnetic nanobead (streptavidin-MNB). The
      streptavidin-MNB played a role of enrichment and separation to achieve a low
      background. The aptamer sequence was employed as a recognition element to bind
      the target adenosine, leading to the releasing of the catalytic stand. Then, the
      catalytic strand induced the Exo III-assisted DNA cycling reaction and produced a
      large amount of DNA fragments, which got a primary amplification. Subsequently,
      the DNA fragments acted as trigger strands to initiate HCR, forming nicked double
      helices with multiple G-quadruplex structures, which achieved a secondary
      amplification. Finally, the G-quadruplex structures bonded with the N-nethyl
      mesopor-phyrin IX (NMM) and yielded an enhanced fluorescence signal, realizing
      the label-free detection. In the proposed strategy, a small amount of adenosine
      can be converted to a large amount of DNA triggers, leading to a significant
      amplification for the target. This method exhibited a high sensitivity toward
      adenosine with a detection limit of 4.2*10(-7) mol L(-1), which was about 10
      times lower than that of the reported label-free strategies. Moreover, this assay
      can significantly distinguish the content of adenosine in urine samples of cancer
      patients and normal human, indicating that our method will offer a new strategy
      for reliable quantification of adenosine in medical research and early clinical
      diagnosis.

PMID- 25775970
TI  - Systemic Manifestations of Hypocomplementemic Urticarial Vasculitis: Comment on
      the Article by Jachiet et al.

PMID- 25775971
TI  - [Cost comparison of two reprocessing procedures of flexible ureteroscopes at the
      University Hospital of Dijon].
AB  - INTRODUCTION: The University Hospital of Dijon has selected sterilization for
      some of its flexible endoscopes. The decision came as part of an acquisition of a
      low-temperature sterilizer. The objective is to compare the actual cost of
      reprocessing a heat-sensitive ureteroscope by sterilization to a high-level
      disinfection (HLD) in semi-automatic bench. MATERIAL AND METHODS: From June 1 to
      December 31, 2013, the ureteroscope has been exclusively reprocessed by low
      temperature sterilization (LTS). In parallel, the theorical number of peracetic
      acid disinfection that should have been made was simulated. An observational
      study of actual costs by micro-costing technique allowed us to determine the set
      of resources consumed by each of these strategies. Specific costs of
      sterilization were from the billing terms provided with the central sterile
      services department. RESULTS: During the 7 months of study, the ureteroscope was
      used and sterilized 11 times. Thirty-two chemical disinfection procedures would
      have been necessary. Comparing these two strategies, a cost difference is
      highlighted for the LTS with a real economy of 43.8% compared with HLD (1154.77 ?
      versus 649.40 ?). CONCLUSION: All in all, this micro-economic study confirms and
      strengthens our previous decision for selecting LTS for heat-sensitive
      ureteroscopes. On top of better micro-economic outcomes, it also provides
      benefits in theoretical risk analysis of transmission of infection.

PMID- 25775972
TI  - ISIBINDI, creating circles of care for orphans and vulnerable children in South
      Africa: post-programme outcomes.
AB  - This paper presents the evaluation of post-programme outcomes of the ISIBINDI
      model, a community-based intervention to promote physical and psychosocial well
      being of orphans and vulnerable children (OVC) in South Africa. A mixed methods
      quasi-experimental design was used to investigate the differences between former
      ISIBINDI participants (18 years and older) and a control group of similar
      background. ISIBINDI ex-participants at 12 sites (n=427) and a control group of
      non-participants (n=177) completed a questionnaire which explored level of
      education and employment, psychosocial well-being and HIV risk behaviour. Focus
      group discussions were conducted with various stakeholders. Ex-participants
      reported higher self-esteem and problem-solving abilities, family support and
      lower HIV risk behaviour than the control group. High levels of unemployment
      especially in rural areas resulted in unemployment of out-of-school OVC which
      creates new forms of vulnerability. The benefits of the programme may be
      compromised by the lack of community resources. An effective exit strategy is
      needed to contribute to financial independence of OVC after exiting the
      programme.

PMID- 25775973
TI  - Telomerase reverse transcriptase potentially promotes the progression of oral
      squamous cell carcinoma through induction of epithelial-mesenchymal transition.
AB  - In recent years, researchers have found the critical role of telomerase in
      cellular transformation, proliferation, stemness and cell survival. High levels
      of telomerase reverse transcriptase (TERT) expression and telomerase activation
      have been reported in most cancer cells. Moreover, overexpression of human TERT
      (hTERT) is reported to be correlated with advanced invasive stage of the tumor
      progression and poor prognosis. Epithelial-mesenchymal transition (EMT),
      characterized by the loss of the cell-cell contact of epithelial cells and the
      acquisition of migratory and motile properties, is known to be a central
      mechanism responsible for invasiveness and metastasis of various cancers. Thus,
      we investigated whether hTERT plays a potential role in the development of EMT.
      As we expected, our clinical results showed that hTERT is overexpressed in oral
      epithelial dysplasia (OED) and OSCC tissues and correlates with clinical
      aggressiveness of oral squamous cell carcinoma (OSCC) patients. We then
      overexpressed hTERT in primary human oral epithelial cells (HOECS) and found that
      hTERT has the potential to prolong the lifespan, a process confering the
      characteristics of EMT by activating the Wnt/beta-catenin pathway. Our findings
      provided an explanation for the aggressive nature of human tumors overexpressing
      hTERT and the possibly mechanism that links hTERT to EMT property, which
      represents a possible therapeutic target in highly metastatic cancers.

PMID- 25775974
TI  - Flipping a G-tetrad in a unimolecular quadruplex without affecting its global
      fold.
AB  - A unimolecular G-quadruplex with a hybrid-type topology and propeller, diagonal,
      and lateral loops was examined for its ability to undergo structural changes upon
      specific modifications. Substituting 2'-deoxy-2'-fluoro analogues with a
      propensity to adopt an anti glycosidic conformation for two or three guanine
      deoxyribonucleosides in syn positions of the 5'-terminal G-tetrad significantly
      alters the CD spectral signature of the quadruplex. An NMR analysis reveals a
      polarity switch of the whole tetrad with glycosidic conformational changes
      detected for all four guanine nucleosides in the modified sequence. As no
      additional rearrangement of the overall fold occurs, a novel type of G-quadruplex
      is formed with guanosines in the four columnar G-tracts lined up in either an all
      syn or an all-anti glycosidic conformation. 

PMID- 25775975
TI  - Cognitive and behavioral outcomes in benign childhood epilepsy with
      centrotemporal spikes.
AB  - We review the evidence that BECTS may be associated with cognitive dysfunction
      and behavioral problems, the extent to which these problems may be associated
      with patterns of EEG abnormalities in BECTS, and the impact of antiepileptic
      medication on cognition and behavior in BECTS. A growing literature examining
      cognitive and behavioral outcomes suggests that children with BECTS perform below
      the level of their peers. Consistent with this, neuroimaging studies reveal that
      BECTS has an impact on structural and functional brain development, but the
      potential influence of frequency and lateralization of centrotemporal spikes
      (CTS) on cognition and behavior is not well understood. Treatment with AEDs is an
      option in BECTS, but existing studies have not clearly shown a clear relationship
      between elimination of CTS and improved cognitive or behavioral outcomes. 

PMID- 25775976
TI  - The platelet serotonin-release assay.
AB  - Few laboratory tests are as clinically useful as The platelet serotonin-release
      assay (SRA): a positive SRA in the appropriate clinical context is virtually
      diagnostic of heparin-induced thrombocytopenia (HIT), a life- and limb
      threatening prothrombotic disorder caused by anti-platelet factor 4 (PF4)/heparin
      antibodies that activate platelets, thereby triggering serotonin-release. The
      SRA's performance characteristics include high sensitivity and specificity,
      although caveats include indeterminate reaction profiles (observed in ~4% of test
      sera) and potential for false-positive reactions. As only a subset of anti
      PF4/heparin antibodies detectable by enzyme-immunoassay (EIA) are additionally
      platelet-activating, the SRA has far greater diagnostic specificity than the EIA.
      However, requiring a positive EIA, either as an initial screening test or as an
      SRA adjunct, will reduce risk of a false-positive SRA (since a negative EIA in a
      patient with a "positive" SRA should prompt critical evaluation of the SRA
      reaction profile). The SRA also provides useful information on whether a HIT
      serum produces strong platelet activation even in the absence of heparin: such
      heparin-"independent" platelet activation is a marker of unusually severe HIT,
      including delayed-onset HIT and severe HIT complicated by consumptive
      coagulopathy with risk for microvascular thrombosis.

PMID- 25775977
TI  - Annexin A2 is SUMOylated on its N-terminal domain: regulation by insulin.
AB  - Insulin receptor (IR) endocytosis requires a remodelling of the actin
      cytoskeleton. We show here that ANXA2 is SUMOylated at the K10 located in a non
      consensus SUMOylation motif in the N-terminal domain. The Y24F mutation decreased
      the SUMOylation signal, whereas insulin stimulation increased ANXA2 SUMOylation.
      A survey of protein SUMOylation in hepatic Golgi/endosome (G/E) fractions after
      insulin injections revealed the presence of a SUMOylation pattern and confirmed
      the SUMOylation of ANXA2. The construction of an IR/ANXA2/SUMO network (IRASGEN)
      in the G/E context reveals the presence of interacting nodes whereby SUMO1
      connects ANXA2 to actin and microtubule-mediated changes in membrane topology.
      Heritable variants associated with type 2 diabetes represent 41% of the IRASGEN
      thus pointing out the physio-pathological importance of this subnetwork. 

PMID- 25775978
TI  - Single chain precursor prohaptoglobin promotes angiogenesis by upregulating
      expression of vascular endothelial growth factor (VEGF) and VEGF receptor2.
AB  - Prohaptoglobin (proHp) is processed into mature haptoglobin via site-specific
      cleavage. Although haptoglobin has been well studied, the functions of proHp
      remain unclear. We investigated the angiogenic action of proHp in endothelial
      cells, demonstrating that proHp upregulated vascular endothelial growth factor
      (VEGF) and VEGF receptor 2 (VEGFR2) expression and endothelial sprouting and
      branching. ProHp-induced sprouting was attenuated by a VEGFR2 inhibitor.
      Moreover, proHp was detected in sera of cancer patients by immunoprecipitation
      and Western blot. These findings indicate that proHp promotes angiogenesis via
      VEGF/VEGFR2 signalling, and serum proHp level may be a useful biomarker for
      diseases associated with angiogenesis. 

PMID- 25775998
TI  - Transient contribution of left posterior parietal cortex to cognitive
      restructuring.
AB  - Cognitive restructuring is a fundamental method within cognitive behavioural
      therapy of changing dysfunctional beliefs into flexible beliefs and learning to
      react appropriately to the reality of an anxiety-causing situation. To clarify
      the neural mechanisms of cognitive restructuring, we designed a unique task that
      replicated psychotherapy during a brain scan. The brain activities of healthy
      male participants were analysed using functional magnetic resonance imaging.
      During the brain scan, participants underwent Socratic questioning aimed at
      cognitive restructuring regarding the necessity of handwashing after using the
      restroom. The behavioural result indicated that the Socratic questioning
      effectively decreased the participants' degree of belief (DOB) that they must
      wash their hands. Alterations in the DOB showed a positive correlation with
      activity in the left posterior parietal cortex (PPC) while the subject thought
      about and rated own belief. The involvement of the left PPC not only in planning
      and decision-making but also in conceptualization may play a pivotal role in
      cognitive restructuring. 

PMID- 25776000
TI  - Congenital Insensitivity to Pain with Anhidrosis in Twin Sisters with
      Sensorineural Deafness.

PMID- 25775999
TI  - Hepatitis B virus pre-S2 mutant large surface protein inhibits DNA double-strand
      break repair and leads to genome instability in hepatocarcinogenesis.
AB  - Although hepatitis B virus (HBV) has been established to cause hepatocellular
      carcinoma (HCC), the exact mechanism remains to be clarified. Type II ground
      glass hepatocytes (GGHs) harbouring the HBV pre-S2 mutant large surface protein
      (LHBS) have been recognized as a morphologically distinct hallmark of HCC in the
      advanced stages of chronic HBV infection. Considering its preneoplastic nature,
      we hypothesized that type II GGH may exhibit high genomic instability, which is
      important for the carcinogenic process in chronic HBV carriers. In this study we
      found that pre-S2 mutant LHBS directly interacted with importin alpha1, the key
      factor that recognizes cargos undergoing nuclear transportation mediated by the
      importin alpha/beta-associated nuclear pore complex (NPC). By interacting with
      importin alpha1, which inhibits its function as an NPC factor, pre-S2 mutant LHBS
      blocked nuclear transport of an essential DNA repair and recombination factor,
      Nijmegen breakage syndrome 1 (NBS1), upon DNA damage, thereby delaying the
      formation of nuclear foci at the sites of DNA double-strand breaks (DSBs). Pre-S2
      mutant LHBS was also found to block NBS1-mediated homologous recombination repair
      and induce multi-nucleation of cells. In addition, pre-S2 mutant LHBS transgenic
      mice showed genomic instability, indicated by increased global gene copy number
      variations (CNVs), which were significantly higher than those in hepatitis B
      virus X mice, indicating that pre-S2 mutant LHBS is the major viral oncoprotein
      inducing genomic instability in HBV-infected hepatocytes. Consistently, the human
      type II GGHs in HCC patients exhibited increased DNA DSBs representing
      significant genomic instability. In conclusion, type II GGHs harbouring HBV pre
      S2 mutant oncoprotein represent a high-risk marker for the loss of genome
      integrity in chronic HBV carriers and explain the complex chromosome changes in
      HCCs. Mouse array CGH raw data: GEO Accession No. GSE61378
      (http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE61378).

PMID- 25776001
TI  - Erratum to: Recent Advances in Febrile Seizures.

PMID- 25776002
TI  - Experience with Continuous Renal Replacement Therapy.
AB  - Information on provision of continuous renal replacement therapy (CRRT) in
      critically ill children from developing countries is limited. The authors
      describe their experience in 17 children with hypotension and acute kidney injury
      (AKI) with fluid overload or electrolyte imbalance managed by 20 sessions of
      CRRT. The median (range) age and weight were 6 y (0.75-18) and 20 kg (6.2-42),
      respectively. All patients were receiving inotropic agents; nine had fluid
      overload (19 %, range 11-34.1 %) and ten had severe AKI. Median clearance and
      filter-life were 2171.4 ml/1.73 m(2)/h (1730.6-4405.8) and 69.7 h (2.8-98.3),
      respectively. Complications were catheter flow related (n = 1), filter clotting
      (n = 3), hemorrhage (n = 3), hypokalemia (n = 16) and hypophosphatemia (n = 11).
      Eight patients (47.1 %) survived; the median PRISM III score of survivors was
      significantly lower than non survivors (10.5 vs.17.0; P 0.02). Renal function
      recovered in the survivors emphasizing the role of this modality in managing
      critically ill patients. 

PMID- 25776003
TI  - The n -> pi* interaction: a rapidly emerging non-covalent interaction.
AB  - This perspective describes the current status of a recently discovered non
      covalent interaction named as the n -> pi* interaction, which is very weak and
      counterintuitive in nature. In this review, we have provided a brief overview of
      the widespread presence of this interaction in biomacromolecules, small
      biomolecules and materials, as well as the physical nature of this interaction
      explored using various experimental and theoretical techniques. It has been found
      that this interaction is equally important to other non-covalent interactions for
      the stability and specific structures of biomolecules and materials. An in-depth
      understanding of this interaction can help in designing more efficient functional
      materials as well as drugs. The review also provides a future outlook in terms of
      exploring the detailed functional role of this interaction in biological
      processes and its direct spectroscopic evidence, which other commonly known non
      covalent interactions (conventional hydrogen bonding, pi-hydrogen bonding, pi
      stacking, etc.) have. 

PMID- 25776004
TI  - Editorial overview: lymphocyte development and activation: lymphocytes,
      integrators of information.

PMID- 25776005
TI  - MoS2-based nanoprobes for detection of silver ions in aqueous solutions and
      bacteria.
AB  - Silver as an extensively used antibacterial agent also poses potential threats to
      the environment and human health. Hence, in this work, we design a fluorescent
      nanoprobe by using rhodamine B isothiocyanate (RhoBS) adsorbed MoS2 nanosheets to
      realize sensitive and selective detection of Ag(+). On the surface of RhoBS
      loaded MoS2 nanosheets, Ag(+) can be reduced to Ag nanoparticles, which afterward
      could not only lead to the detachment of RhoBS molecules and thus their recovered
      fluorescence but also the surface-enhanced fluorescence from RhoBS remaining
      adsorbed on MoS2. Such an interesting mechanism allows highly sensitive detection
      of Ag(+) (down to 10 nM) with great selectivity among other metal ions. Moreover,
      we further demonstrate that our MoS2-RhoBS complex could act as a nontoxic
      nanoprobe to detect Ag(+) in live bacteria samples. Our work resulted from an
      unexpected finding and suggests the promise of two-dimensional transition-metal
      sulfide nanosheets as a novel platform for chemical and biological sensing. 

PMID- 25776006
TI  - Modular construction of size-selected multiple-core Pt-TiO2 nanoclusters for
      electro-catalysis.
AB  - Size-selected binary platinum-titanium dioxide (Pt-TiO2) clusters have been
      generated using a magnetron sputtering gas condensation cluster source and imaged
      using a Scanning Transmission Electron Microscope (STEM) in High Angle Annular
      Dark Field (HAADF) mode. The core-shell clusters exhibit a Pt core of preferred
      size 30 +/- 6 atoms (1 nm), embedded in an oxidised Ti shell, independent of the
      overall cluster size (varied between 2 nm and 5 nm). Smaller clusters, with mass
      <=50 000 Daltons, show a single Pt core while larger clusters, >=55 000 Daltons,
      feature multiple Pt cores, either isolated or aggregated within the TiO2 shell.
      These clusters may have applications in solar hydrogen production; preliminary
      work indicates catalytic active in the hydrogen evolution reaction. 

PMID- 25776007
TI  - DAW22, a natural sesquiterpene coumarin isolated from Ferula ferulaeoides
      (Steud.) Korov. that induces C6 glioma cell apoptosis and endoplasmic reticulum
      (ER) stress.
AB  - 2,3-Dihydro-7-hydroxy-2R*,3R*-dimethyl-2-[4,8-dimethyl-3(E),7-nonadienyl]
      furo[3,2-c]coumarin (named DAW22), a sesquiterpene coumarin isolated from the
      roots of Ferula ferulaeoides (Steud.) Korov., has been reported to bear anti
      proliferative activities toward different types of cancer cells. In this study,
      we demonstrated that DAW22 induced apoptosis in C6 glioma cells. Subsequently, we
      found that DAW22-induced apoptosis in C6 glioma cells occurred via the
      mitochondria-mediated and death-receptor pathways. Moreover, we found a massive
      cytoplasmic vacuolization, a dramatic change of endoplasmic reticulum (ER), up
      regulation of CHOP and cleavage of caspase-12, suggesting that DAW22-induced
      apoptosis is involved in ER stress. In addition, we revealed that DAW22 treatment
      induced the activation of PERK, ATF6alpha and IRE1alpha. We further found that
      knockdown of CHOP affected DAW22-induced apoptosis, and DAW22-stimulated down
      regulation of Bcl-2, caspase-8 activation and PARP cleavage were inhibited. Taken
      together, these results demonstrate that DAW22 induces apoptosis by ER stress and
      mitochondrial/death-receptor pathways, which may provide a new clue for
      exploiting this compound as a potential anti-neoplastic drug in future glioma
      cancer therapy. 

PMID- 25776008
TI  - Coriander (Coriandrum sativum L.) and its bioactive constituents.
AB  - Coriander (Coriandrum sativum L.), a member of the Apiaceae family, is among most
      widely used medicinal plant, possessing nutritional as well as medicinal
      properties. Thus, the aim of this updated review is to highlight the importance
      of coriander as a potential source of bioactive constituents and to summarize
      their biological activities as well as their different applications from data
      obtained in recent literature, with critical analysis on the gaps and potential
      for future investigations. A literature review was carried out by searching on
      the electronic databases including PubMed, Scopus, ScienceDirect, and Google
      Scholar for studies focusing on the biological and pharmacological activities of
      coriander seed and herb bioactive constituents. All recent English-language
      articles published between 2000 and 2014 were searched using the terms 'C.
      sativum', 'medicinal plant', 'bioactive constituents', and 'biological
      activities'. Subsequently, coriander seed and herb essential oils have been
      actively investigated for their chemical composition and biological activities
      including antimicrobial, antioxidant, hypoglycemic, hypolipidemic, anxiolytic,
      analgesic, anti-inflammatory, anti-convulsant and anti-cancer activities, among
      others. Although coriander has been reported to possess a wide range of
      traditional medicinal uses, no report is available in its effectiveness use in
      reactive airway diseases such as asthma and bronchiolitis. In brief, the
      information presented herein will be helpful to create more interest towards this
      medicinal species by defining novel pharmacological and clinical applications and
      hence, may be useful in developing new drug formulations in the future or by
      employing coriander bioactive constituents in combination with conventional drugs
      to enhance the treatment of diseases such as Alzheimer and cancer. 

PMID- 25776009
TI  - A novel TAZ gene mutation and mosaicism in a Polish family with Barth syndrome.
AB  - Barth syndrome (BTHS) is an X-linked recessive disease primarily affecting males.
      Clinically, the disease is characterized by hypertrophic or dilated
      cardiomyopathy, skeletal myopathy, chronic/cyclic neutropenia, 3-methylglutaconic
      aciduria, growth retardation and respiratory chain dysfunction. It is caused by
      mutations in the TAZ gene coding for the tafazzin protein which is responsible
      for cardiolipin remodeling. In this work, we present a novel pathogenic TAZ
      mutation c.83T>A, p.Val28Glu, found in mosaic form in almost all female members
      of a Polish family. Sanger sequencing of DNA from peripheral blood and from
      epithelial cells showed female mosaicism in three generations. This appears to be
      a new mechanism of inheritance and further research is required in order to
      understand the mechanism of this mosaicism. We conclude that BTHS genetic testing
      should include two or more tissues for women that appear to be noncarriers when
      blood DNA is initially tested. The results of our study should not only be
      applicable to BTHS families, but also to families with other X-linked diseases. 

PMID- 25776010
TI  - A probable case of gigantism/acromegaly in skeletal remains from the Jewish
      necropolis of "Ronda Sur" (Lucena, Cordoba, Spain; VIII-XII centuries CE).
AB  - Pituitary gigantism is a rare endocrine disorder caused by hypersecretion of
      growth hormone during growing period. Individuals with this disorder have an
      enormous growth in height and associated degenerative changes. The continued
      hypersecretion of growth hormone during adulthood leads to acromegaly, a
      condition related to the disproportionate bone growth of the skull, hands and
      feet. The skeletal remains studied belong to a young adult male from the Jewish
      necropolis of "Ronda Sur" in Lucena (Cordoba, Spain, VIII-XII centuries CE). The
      individual shows a very large and thick neurocranium, pronounced supraorbital
      ridges, an extremely prominent occipital protuberance, and an extremely large and
      massive mandible. Additional pathologies include enlargement of the vertebral
      bodies with degenerative changes, thickened ribs, and a slight increased length
      of the diaphysis with an increased cortical bone thickness of lower limbs.
      Comparative metric analysis of the mandible with other individuals from the same
      population and a contemporary Mediterranean population shows a trend toward
      acromegalic morphology. This case is an important contribution in
      paleopathological literature because it is a rare condition that has not been
      widely documented in ancient skeletal remains. 

PMID- 25776011
TI  - Ensemble-based source apportionment of fine particulate matter and emergency
      department visits for pediatric asthma.
AB  - Epidemiologic studies utilizing source apportionment (SA) of fine particulate
      matter have shown that particles from certain sources might be more detrimental
      to health than others; however, it is difficult to quantify the uncertainty
      associated with a given SA approach. In the present study, we examined
      associations between source contributions of fine particulate matter and
      emergency department visits for pediatric asthma in Atlanta, Georgia (2002-2010)
      using a novel ensemble-based SA technique. Six daily source contributions from 4
      SA approaches were combined into an ensemble source contribution. To better
      account for exposure uncertainty, 10 source profiles were sampled from their
      posterior distributions, resulting in 10 time series with daily SA
      concentrations. For each of these time series, Poisson generalized linear models
      with varying lag structures were used to estimate the health associations for the
      6 sources. The rate ratios for the source-specific health associations from the
      10 imputed source contribution time series were combined, resulting in health
      associations with inflated confidence intervals to better account for exposure
      uncertainty. Adverse associations with pediatric asthma were observed for 8-day
      exposure to particles generated from diesel-fueled vehicles (rate ratio = 1.06,
      95% confidence interval: 1.01, 1.10) and gasoline-fueled vehicles (rate ratio =
      1.10, 95% confidence interval: 1.04, 1.17).

PMID- 25776013
TI  - Is the inverse association between selenium and bladder cancer due to confounding
      by smoking?
AB  - Selenium has been linked to a reduced risk of bladder cancer in some studies.
      Smoking, a well-established risk factor for bladder cancer, has been associated
      with lower selenium levels in the body. We investigated the selenium-bladder
      cancer association in subjects from Maine, New Hampshire, and Vermont in the New
      England Bladder Cancer Case-Control Study. At interview (2001-2005), participants
      provided information on a variety of factors, including a comprehensive smoking
      history, and submitted toenail samples, from which we measured selenium levels.
      We estimated odds ratios and 95% confidence intervals among 1,058 cases and 1,271
      controls using logistic regression. After controlling for smoking, we saw no
      evidence of an association between selenium levels and bladder cancer (for fourth
      quartile vs. first quartile, odds ratio (OR) = 0.98, 95% confidence interval
      (CI): 0.77, 1.25). When results were restricted to regular smokers, there
      appeared to be an inverse association (OR = 0.76, 95% CI: 0.58, 0.99); however,
      when pack-years of smoking were considered, this association was attenuated (OR =
      0.91, 95% CI: 0.68, 1.20), indicating potential confounding by smoking. Despite
      some reports of an inverse association between selenium and bladder cancer
      overall, our results, combined with an in-depth evaluation of other studies,
      suggested that confounding from smoking intensity or duration could explain this
      association. Our study highlights the need to carefully evaluate the confounding
      association of smoking in the selenium-bladder cancer association.

PMID- 25776014
TI  - Case history and genome-wide scans for copy number variants in a family with
      patient having 15q11.1-q11.2 duplication and 22q11.2 deletion, and schizophrenia.
AB  - Many studies have indicated that chromosomes 15q11 and 22q11 may be associated
      with the genetic etiologies of schizophrenia. We have followed an adult
      schizophrenia case with 15q11.1-q11.2 duplication and 22q11.2 deletion. Here we
      report his clinical history, and copy number variants (CNVs) identified by
      microarray and real-time PCR in the patient and his parents. This is the first
      report describing a detailed phenotype of an adult schizophrenic case with both
      15q11 and 22q11 CNVs as revealed by novel and trustworthy technologies. Subjects
      were a 33-year-old male patient with 15q11 and 22q11 CNVs, and his normal
      parents. He fulfilled the DSM-IV criteria for schizophrenia at age 18 years. He
      was also diagnosed with 22q11.2 deletion syndrome by fluorescence in situ
      hybridization (FISH) at age 18 years. To search for CNVs in more detail, whole
      genome array-CGH analyses including ~ 420,000 probes were carried out in the
      patient and his parents. For validations of the CNVs detected by array-CGH, real
      time PCR analyses of these CNVs were performed. The patient had two disease
      specific CNVs, 15q11.1-q11.2 duplication (~ 2.7 Mb) and 22q11.21 deletion (~ 2.9
      Mb). These two regions are important for the development of schizophrenia, and
      this patient had shown symptoms of schizophrenia. Thus, the two areas may contain
      causal genes for schizophrenia.

PMID- 25776015
TI  - Electrodeposition of hierarchically structured three-dimensional nickel-iron
      electrodes for efficient oxygen evolution at high current densities.
AB  - Large-scale industrial application of electrolytic splitting of water has called
      for the development of oxygen evolution electrodes that are inexpensive, robust
      and can deliver large current density (>500 mA cm(-2)) at low applied potentials.
      Here we show that an efficient oxygen electrode can be developed by
      electrodepositing amorphous mesoporous nickel-iron composite nanosheets directly
      onto macroporous nickel foam substrates. The as-prepared oxygen electrode
      exhibits high catalytic activity towards water oxidation in alkaline solutions,
      which only requires an overpotential of 200 mV to initiate the reaction, and is
      capable of delivering current densities of 500 and 1,000 mA cm(-2) at
      overpotentials of 240 and 270 mV, respectively. The electrode also shows
      prolonged stability against bulk water electrolysis at large current.
      Collectively, the as-prepared three-dimensional structured electrode is the most
      efficient oxygen evolution electrode in alkaline electrolytes reported to the
      best of our knowledge, and can potentially be applied for industrial scale water
      electrolysis. 

PMID- 25776016
TI  - Strategies for improving sensitivity and selectivity for the quantitation of
      biotherapeutics in biological matrix using LC-MS/MS.
AB  - In recent years, the applicability of using LC-MS/MS as a complementary technique
      to traditional ligand binding assays in the absolute quantitation of therapeutic
      proteins in biologic matrix has been demonstrated. Protein quantitation workflow
      via LC-MS/MS is primarily based on a enzymatic digestion model and recent works
      seek to improve selectivity and sensitivity. This review focuses on recent
      innovations in this field and discusses the following in detail: the
      applicability of two-dimensional liquid chromatography and its use to improve
      sensitivity and alleviate matrix ion suppression; the use of derivatization
      agents after digestion to improve extraction and MS ionization efficiency;
      techniques to reduce excess protein background and their positive effects on
      sensitivity, selectivity, and extraction consistency; the application of
      immunoaffinity extraction of proteins to enrich the analyte(s) of interest while
      improving selectivity and sensitivity.

PMID- 25776017
TI  - MR mammography using diffusion-weighted imaging in evaluating breast cancer: a
      correlation with proliferation index.
AB  - PURPOSE: To evaluate whether the variation of the apparent diffusion coefficient
      (ADC) values obtained with DWI can predict elevated levels of Ki67 proliferation
      index and aggressive subtypes in patients with breast cancer. MATERIALS AND
      METHODS: Breast MRI studies of 115 patients (mean age 57.3 years, range 36-81
      years) with a biopsy-proven breast cancers were evaluated in this retrospective
      IRB-approved study. Examinations were performed on a 1.5 T magnet and included a
      Single-Shot Echoplanar DWI sequence with b values of 0 and 1000 s/mm(2). For each
      target lesion, ADC was measured. ADC values were compared considering Ki67 status
      (>=20 % or <20 %), histology, grade (G1, G2 or G3) and clinical-pathological
      classification (Luminal A, Luminal B HER2-positive, Luminal B HER-2 negative, HER
      2 enriched and Triple Negative). Mann-Whitney U test and Kruskal-Wallis test were
      used for comparisons and receiver operating characteristic (ROC) curves were
      obtained. Inter- and intra-reader variability was evaluated in a subset of 40
      patients, using interclass correlation coefficient (ICC) and Bland-Altman plots.
      RESULTS: Of 115 lesions, 53 (46.1 %) were assessed as Ki67 positive and 62 (53.9
      %) as Ki67 negative. ADC values were significantly (p < 0.0001) lower in Ki67
      positive patients (median 0.86 * 10(-3) mm(2)/s; interquartile range 0.75-0.92)
      compared to Ki67-negative (median 1.03 * 10(-3) mm(2)/s; interquartile range 0.92
      1.13). Median ADC was also lower in G2 and G3 cancer and in the Luminal B Her2
      negative subtype (p = 0.0015). No differences were found when evaluating
      histology. ROC curve showed a sensitivity and specificity of 83.0 and 66.1 %,
      respectively, when using a cutoff of 0.95 s/mm(2) to differentiate Ki67-positive
      from Ki67-negative cancers. Inter- and intra-reader variability was moderate (ICC
      = 0.623; ICC = 0.548, respectively). No systematic differences were identified
      with Bland-Altman plots. CONCLUSIONS: Lower ADC values are associated with
      elevated Ki67 proliferation index and more aggressive pathologic features.
      Moderate agreement in ADC measurement could be a limitation.

PMID- 25776018
TI  - Imaging for homicide investigations.
AB  - The authors present the opportunities of the application of post-mortem imaging,
      focusing on post-mortem computed tomography and post-mortem computed tomography
      angiography in modern forensic investigation of homicide cases. The paper is
      based on scientific publications related to the subject from ca. the past 10
      years, supplemented by the authors' own experiences. The article is illustrated
      with reconstructions based on the authors' own cases related to homicide due to
      ballistic/sharp/blunt trauma. As is shown, the results of evaluation of post
      mortem computed tomography allow better diagnosis, documentation and
      visualisation of forensic examinations.

PMID- 25776019
TI  - Targeting Structural Change for HIV Prevention: A Process and Tool for Community
      Application.
AB  - To address the persistent HIV epidemic in the United States, prevention efforts
      are focusing on social determinants related to HIV risk by targeting systems and
      structures, such as organizational and institutional policies, practices and
      programs, and legislative and regulatory approaches to modify features of the
      environment that influence HIV risk. With limited evidenced-based examples,
      communities can benefit from strategic planning resources that help them consider
      developing structural-level changes that target root causes of HIV risk. In this
      article, we present the Connect to Protect(r) project that outlines a process and
      a tool to move from general ideas to specific structural changes. Examples from
      14 coalitions are also provided. Using the process and tools presented here can
      provide a launching pad for other coalitions seeking to build an HIV prevention
      agenda and for practitioners seeking to incorporate structural changes for
      community health promotion. 

PMID- 25776020
TI  - Shared resources, shared costs--leveraging biocuration resources.
AB  - The manual curation of the information in biomedical resources is an expensive
      task. This article argues the value of this approach in comparison with other
      apparently less costly options, such as automated annotation or text-mining, then
      discusses ways in which databases can make cost savings by sharing infrastructure
      and tool development. Sharing curation effort is a model already being adopted by
      several data resources. Approaches taken by two of these, the Gene Ontology
      annotation effort and the IntAct molecular interaction database, are reviewed in
      more detail. These models help to ensure long-term persistence of curated data
      and minimizes redundant development of resources by multiple disparate groups.

PMID- 25776021
TI  - Ontology application and use at the ENCODE DCC.
AB  - The Encyclopedia of DNA elements (ENCODE) project is an ongoing collaborative
      effort to create a catalog of genomic annotations. To date, the project has
      generated over 4000 experiments across more than 350 cell lines and tissues using
      a wide array of experimental techniques to study the chromatin structure,
      regulatory network and transcriptional landscape of the Homo sapiens and Mus
      musculus genomes. All ENCODE experimental data, metadata and associated
      computational analyses are submitted to the ENCODE Data Coordination Center (DCC)
      for validation, tracking, storage and distribution to community resources and the
      scientific community. As the volume of data increases, the organization of
      experimental details becomes increasingly complicated and demands careful
      curation to identify related experiments. Here, we describe the ENCODE DCC's use
      of ontologies to standardize experimental metadata. We discuss how ontologies,
      when used to annotate metadata, provide improved searching capabilities and
      facilitate the ability to find connections within a set of experiments.
      Additionally, we provide examples of how ontologies are used to annotate ENCODE
      metadata and how the annotations can be identified via ontology-driven searches
      at the ENCODE portal. As genomic datasets grow larger and more interconnected,
      standardization of metadata becomes increasingly vital to allow for exploration
      and comparison of data between different scientific projects.

PMID- 25776022
TI  - RNABP COGEST: a resource for investigating functional RNAs.
AB  - Structural bioinformatics of RNA has evolved mainly in response to the rapidly
      accumulating evidence that non-(protein)-coding RNAs (ncRNAs) play critical roles
      in gene regulation and development. The structures and functions of most ncRNAs
      are however still unknown. Most of the available RNA structural databases rely
      heavily on known 3D structures, and contextually correlate base pairing geometry
      with actual 3D RNA structures. None of the databases provide any direct
      information about stabilization energies. However, the intrinsic interaction
      energies of constituent base pairs can provide significant insights into their
      roles in the overall dynamics of RNA motifs and structures. Quantum mechanical
      (QM) computations provide the only approach toward their accurate quantification
      and characterization. 'RNA Base Pair Count, Geometry and Stability'
      (http://bioinf.iiit.ac.in/RNABPCOGEST) brings together information, extracted
      from literature data, regarding occurrence frequency, experimental and quantum
      chemically optimized geometries, and computed interaction energies, for non
      canonical base pairs observed in a non-redundant dataset of functional RNA
      structures. The database is designed to enable the QM community, on the one hand,
      to identify appropriate biologically relevant model systems and also enable the
      biology community to easily sift through diverse computational results to gain
      theoretical insights which could promote hypothesis driven biological research.

PMID- 25776023
TI  - EpiDBase: a manually curated database for small molecule modulators of epigenetic
      landscape.
AB  - We have developed EpiDBase (www.epidbase.org), an interactive database of small
      molecule ligands of epigenetic protein families by bringing together
      experimental, structural and chemoinformatic data in one place. Currently,
      EpiDBase encompasses 5784 unique ligands (11 422 entries) of various epigenetic
      markers such as writers, erasers and readers. The EpiDBase includes experimental
      IC(50) values, ligand molecular weight, hydrogen bond donor and acceptor count,
      XlogP, number of rotatable bonds, number of aromatic rings, InChIKey, two
      dimensional and three-dimensional (3D) chemical structures. A catalog of all
      epidbase ligands based on the molecular weight is also provided. A structure
      editor is provided for 3D visualization of ligands. EpiDBase is integrated with
      tools like text search, disease-specific search, advanced search, substructure,
      and similarity analysis. Advanced analysis can be performed using substructure
      and OpenBabel-based chemical similarity fingerprints. The EpiDBase is curated to
      identify unique molecular scaffolds. Initially, molecules were selected by
      removing peptides, macrocycles and other complex structures and then processed
      for conformational sampling by generating 3D conformers. Subsequent filtering
      through Zinc Is Not Commercial (ZINC: a free database of commercially available
      compounds for virtual screening) and Lilly MedChem regular rules retained many
      distinctive drug-like molecules. These molecules were then analyzed for
      physicochemical properties using OpenBabel descriptors and clustered using
      various methods such as hierarchical clustering, binning partition and
      multidimensional scaling. EpiDBase provides comprehensive resources for further
      design, development and refinement of small molecule modulators of epigenetic
      markers.

PMID- 25776024
TI  - LMPID: a manually curated database of linear motifs mediating protein-protein
      interactions.
AB  - Linear motifs (LMs), used by a subset of all protein-protein interactions (PPIs),
      bind to globular receptors or domains and play an important role in signaling
      networks. LMPID (Linear Motif mediated Protein Interaction Database) is a
      manually curated database which provides comprehensive experimentally validated
      information about the LMs mediating PPIs from all organisms on a single platform.
      About 2200 entries have been compiled by detailed manual curation of PubMed
      abstracts, of which about 1000 LM entries were being annotated for the first
      time, as compared with the Eukaryotic LM resource. The users can submit their
      query through a user-friendly search page and browse the data in the alphabetical
      order of the bait gene names and according to the domains interacting with the
      LM. LMPID is freely accessible at http://bicresources.jcbose. ac.in/ssaha4/lmpid
      and contains 1750 unique LM instances found within 1181 baits interacting with
      552 prey proteins. In summary, LMPID is an attempt to enrich the existing
      repertoire of resources available for studying the LMs implicated in PPIs and may
      help in understanding the patterns of LMs binding to a specific domain and
      develop prediction model to identify novel LMs specific to a domain and further
      able to predict inhibitors/modulators of PPI of interest.

PMID- 25776025
TI  - An update on clinicopathological, immunohistochemical, and molecular profiles of
      colloid carcinoma of the lung.
AB  - Colloid carcinoma is a rare subtype of lung adenocarcinoma characterized by
      abundant pools of extracellular mucin and scant malignant epithelium. Because of
      the rarity of these tumors, many of the reported clinicopathological and
      immunohistochemical characteristics are contradictory. Moreover, the molecular
      alterations that underlie these tumors are unknown. We present the
      clinicopathological, immunohistochemical, and molecular features of 13 cases of
      colloid carcinoma of the lung. The patients were 9 women and 4 men between the
      ages of 48 and 86 years. Surgical resection and staging were performed in all
      patients. Seven patients were in stage T1N0M0, 3 in T2N0M0, 2 in T2N1M0, and 1 in
      T2N0M1. The tumor was 100% mucinous in 9 patients, whereas in 4 cases, the
      lesions consisted of 50% to 90% mucin pools with the remainder being a noncolloid
      adenocarcinoma component ranging in morphology from bronchioalveolar to acinar,
      papillary, solid, or mixed patterns. Follow-up ranged from 35 to 128 months.
      Three patients died, 1 of disease and 2 of unrelated causes. The remaining 10
      patients are alive at the time of reporting, 3 with recurrent disease.
      Immunohistochemical studies showed CK7, CK20, and CDX2 expression in all tumors,
      whereas TTF-1, surfactant A, and napsin A were not present or were only focally
      positive in most cases. Analysis showed KRAS mutations in 2 cases. All tumors
      were negative for ALK gene rearrangement and EGFR mutation. Our study highlights
      the clinicopathological, immunohistochemical, and molecular features of lung
      colloid adenocarcinoma and attempts to clarify some misconceptions regarding this
      rare tumor. 

PMID- 25776026
TI  - Frameshift mutations in mammalian target of rapamycin pathway genes and their
      regional heterogeneity in sporadic colorectal cancers.
AB  - Mammalian target of rapamycin (mTOR) pathway is known to be involved in cancer
      pathogenesis. The aim of our study was to find whether mTOR-related genes were
      mutated and expressionally altered in colorectal cancers (CRCs). Through public
      database searching, we found that PIK3CB, insulin receptor substrate 1/2 (IRS1),
      RPS6, EIF4B, RPS6KA5, and PRKAA2 that were known as mTOR-related genes possessed
      mononucleotide repeats in DNA coding sequences that could be mutated in cancers
      with microsatellite instability (MSI). We analyzed 124 CRCs by single-strand
      conformation polymorphism analysis and DNA sequencing and found 7 (8.9%), 8
      (10.1%), and 3 (3.8%) of 79 CRCs with high MSI that harbored IRS1, EIF4B, and
      RPS6KA5 frameshift mutations, respectively. These mutations were not identified
      in stable MSI/low MSI (0/45). In addition, we analyzed intratumoral heterogeneity
      (ITH) of PIK3CB, IRS1, RPS6, EIF4B, RPS6KA5, and PRKAA2 frameshift mutations in
      16 CRCs and found that IRS1, EIF4B, and RPS6KA5 mutations had regional ITH in 2,
      2, and 1 CRCs, respectively. We also analyzed IRS1 expression in the CRCs by
      immunohistochemistry. Loss of IRS1 expression was identified in 31% of the CRCs.
      The loss of expression was more common in those with IRS1 mutation than those
      with wild-type IRS1. Our data indicate mTOR-related genes harbored not only
      somatic mutations but also mutational ITH and loss of expression, which together
      might play a role in tumorigenesis of CRC, especially with high MSI. Our data
      also suggest that mutation analysis in multiregional areas is needed for a
      precise evaluation of mutation status in CRC with MSI-H. 

PMID- 25776027
TI  - Accuracy of classifying poorly differentiated non-small cell lung carcinoma
      biopsies with commonly used lung carcinoma markers.
AB  - Immunohistochemical (IHC) staining is an important adjunct to the classification
      of non-small cell lung carcinoma (NSCLC). Several studies have used tissue
      microarrays derived from resection specimens to evaluate the accuracy of IHC
      staining for classifying NSCLC, but few have used actual biopsies of poorly
      differentiated carcinomas, and the question of how often biopsy IHC in such
      tumors leads to the correct classification has received little attention. We
      identified 40 cases of NSCLC that, on biopsy, could not be subclassified by
      morphology and that had subsequent resection specimens. TTF-1, napsin, p63/p40,
      and CK5 or a subset thereof were used for IHC classification. Of the 40 cases
      classified by IHC on biopsy, 33 (82%) had no change in diagnosis after resection.
      Of the remaining 7 cases, 3 were classified as NSCLC--not otherwise specified on
      biopsy and subclassified as either adenocarcinoma or squamous cell carcinoma
      (SCC) on the surgical specimen. One adenocarcinoma biopsy was reclassified as
      pleomorphic carcinoma. Two SCCs were changed to adenosquamous carcinoma, and 1
      SCC was changed to large cell lung carcinoma. Only 1 antibody pair (2%) was
      discordant between biopsy, and almost all reclassifications were done based on
      morphologic features rather than change in IHC pattern. We conclude that IHC
      staining allows accurate subclassification of poorly differentiated NSCLCs on
      small lung biopsies in most cases, but there is still a substantial "miss" rate
      (here, 18%). Surgical resection specimens allow further subclassification, mainly
      due to architectural features not present in the biopsies.

PMID- 25776028
TI  - Exit competencies in pathology and laboratory medicine for graduating medical
      students: the Canadian approach.
AB  - Physicians in every medical and surgical field must be able to use pathology
      concepts and skills in their practice: for example, they must order and interpret
      the correct laboratory tests, they must use their understanding of pathogenesis
      to diagnose and treat, and they must work with the laboratory to care for their
      patients. These important concepts and skills may be ignored by medical schools
      and even national/international organizations setting graduation expectations for
      medical students. There is an evolving international consensus about the
      importance of exit competencies for medical school graduates, which define the
      measurable or observable behaviors each graduate must be able to demonstrate. The
      Canadian Association of Pathologists (CAP) Education Group set out to establish
      the basic competencies in pathology and laboratory medicine which should be
      expected of every medical graduate: not competencies for pathologists, but for
      medical graduates who intend to enter any residency program. We defined 4 targets
      for pathology and laboratory medicine exit competencies: that they represent only
      measurable behaviors, that they be clinically focused, that they be generalizable
      to every medical graduate, and that the final competency document be user
      friendly. A set of competencies was developed iteratively and underwent final
      revision at the 2012 CAP annual meeting. These competencies were subsequently
      endorsed by the CAP executive and the Canadian Leadership Council on Laboratory
      Medicine. This clinically focused consensus document provides the first
      comprehensive list of exit competencies in pathology and laboratory medicine for
      undergraduate medical education. 

PMID- 25776029
TI  - Immunohistochemical expression of ARID1A in penile squamous cell carcinomas: a
      tissue microarray study of 112 cases.
AB  - ARID1A, a member of the chromatin remodeling genes family, has been suggested as
      a novel tumor suppressor gene in gynecologic malignancies. However, its role in
      penile cancer has yet to be determined. This study assesses the
      immunohistochemical expression of ARID1A in penile squamous cell carcinoma (SCC)
      and its association with pathologic features, human papillomavirus (HPV) status,
      and previously reported mammalian target of rapamycin pathway markers in the same
      cohort. Four tissue microarrays were constructed from 112 cases of formalin
      fixed, paraffin-embedded penile SCC from Paraguay. Each tumor was sampled 3 to 12
      times. ARID1A expression was evaluated by immunohistochemistry using a polyclonal
      rabbit anti-ARID1A (BAF250A) antibody. An H score was calculated in each spot as
      the sum of expression intensity (0-3+) by extent (0%-100%). Median H score per
      case was used for statistical analysis. ARID1A expression was observed in all
      cases, ranging from 3% to 100% of tumor cells (median, 95%). In 96 cases (86%),
      ARID1A expression was observed in 90% or more tumor cells. HPV DNA was detected
      in 20 (38%) of 52 analyzed samples. There was a significant trend of association
      between ARID1A and histologic grade. ARID1A expression was not associated with
      histologic subtype (P = .61) or HPV status (P = .18). ARID1A expression decreased
      with decreasing levels of PTEN expression (P = .01). ARID1A was expressed in
      penile SCC, in most cases at high levels. A significant trend of association was
      found between histologic grade and ARID1A expression, with lower ARID1A
      expression, lower histologic grades, and decreased PTEN expression. 

PMID- 25776030
TI  - Automatic quantification of lobular inflammation and hepatocyte ballooning in
      nonalcoholic fatty liver disease liver biopsies.
AB  - Automatic quantification of cardinal histologic features of nonalcoholic fatty
      liver disease (NAFLD) may reduce human variability and allow continuous rather
      than semiquantitative assessment of injury. We recently developed an automated
      classifier that can detect and quantify macrosteatosis with greater than or equal
      to 95% precision and recall (sensitivity). Here, we report our early results on
      the classifier's performance in detecting lobular inflammation and hepatocellular
      ballooning. Automatic quantification of lobular inflammation and ballooning was
      performed on digital images of hematoxylin and eosin-stained slides of liver
      biopsy samples from 59 individuals with normal liver histology and varying
      severity of NAFLD. Two expert hepatopathologists scored liver biopsies according
      the nonalcoholic steatohepatitis clinical research network scoring system and
      provided annotations of lobular inflammation and hepatocyte ballooning on the
      digital images. The classifier had precision and recall of 70% and 49% for
      lobular inflammation, and 91% and 54% for hepatocyte ballooning. In addition, the
      classifier had an area under the curve of 95% for lobular inflammation and 98%
      for hepatocyte ballooning. The Spearman rank correlation coefficient for
      comparison with pathologist grades was 45.2% for lobular inflammation and 46% for
      hepatocyte ballooning. Our novel observations demonstrate that automatic
      quantification of cardinal NAFLD histologic lesions is feasible and offer promise
      for further development of automatic quantification as a potential aid to
      pathologists evaluating NAFLD biopsies in clinical practice and clinical trials. 

PMID- 25776031
TI  - Thermal effects of 2450 MHz microwave exposure near a titanium alloy plate
      implanted in rabbit limbs.
AB  - This study aimed to examine the safety profile of microwave therapy on limbs with
      metal implants. New Zealand white rabbits were implanted with titanium alloy
      internal fixation plates. Femurs were exposed to 20, 40, 60, or 80 W of microwave
      radiation for 30 min (microwave applicator at 2450 MHz), and temperatures of the
      implants and muscles adjacent to implants were recorded. To evaluate thermal
      damage, nerves were electrodiagnostically assessed immediately after radiation,
      and histologic studies performed on nerve and muscle sections. As expected,
      implant temperature was highest in the exposure field. Temperatures of limbs with
      titanium alloy implants increased significantly at 60 and 80 W, with a
      significant decline in the nerve conduction velocity and acute thermal injuries
      in nerves and muscles adjacent to implants. However, temperature remained
      unchanged and no adverse effects were observed in nerves and muscles at 20 and 40
      W. These findings are inconsistent with the current notion that surgical metal
      implants in the treatment field are contraindications for microwave therapy.
      Hence, we believe that a lower dose of continuous wave microwave irradiation is
      safe for limbs with titanium alloy implants.

PMID- 25776032
TI  - Practical approaches for design and analysis of clinical trials of infertility
      treatments: crossover designs and the Mantel-Haenszel method are recommended.
AB  - Crossover designs have some advantages over standard clinical trial designs and
      they are often used in trials evaluating the efficacy of treatments for
      infertility. However, clinical trials of infertility treatments violate a
      fundamental condition of crossover designs, because women who become pregnant in
      the first treatment period are not treated in the second period. In previous
      research, to deal with this problem, some new designs, such as re-randomization
      designs, and analysis methods including the logistic mixture model and the beta
      binomial mixture model were proposed. Although the performance of these designs
      and methods has previously been evaluated in large-scale clinical trials with
      sample sizes of more than 1000 per group, the actual sample sizes of infertility
      treatment trials are usually around 100 per group. The most appropriate design
      and analysis for these moderate-scale clinical trials are currently unclear. In
      this study, we conducted simulation studies to determine the appropriate design
      and analysis method of moderate-scale clinical trials for irreversible endpoints
      by evaluating the statistical power and bias in the treatment effect estimates.
      The Mantel-Haenszel method had similar power and bias to the logistic mixture
      model. The crossover designs had the highest power and the smallest bias. We
      recommend using a combination of the crossover design and the Mantel-Haenszel
      method for two-period, two-treatment clinical trials with irreversible endpoints.

PMID- 25776033
TI  - Inclusion of quasi-experimental studies in systematic reviews of health systems
      research.
AB  - Systematic reviews of health systems research commonly limit studies for evidence
      synthesis to randomized controlled trials. However, well-conducted quasi
      experimental studies can provide strong evidence for causal inference. With this
      article, we aim to stimulate and inform discussions on including quasi
      experiments in systematic reviews of health systems research. We define quasi
      experimental studies as those that estimate causal effect sizes using exogenous
      variation in the exposure of interest that is not directly controlled by the
      researcher. We incorporate this definition into a non-hierarchical three-class
      taxonomy of study designs - experiments, quasi-experiments, and non-experiments.
      Based on a review of practice in three disciplines related to health systems
      research (epidemiology, economics, and political science), we discuss five
      commonly used study designs that fit our definition of quasi-experiments: natural
      experiments, instrumental variable analyses, regression discontinuity analyses,
      interrupted times series studies, and difference studies including controlled
      before-and-after designs, difference-in-difference designs and fixed effects
      analyses of panel data. We further review current practices regarding quasi
      experimental studies in three non-health fields that utilize systematic reviews
      (education, development, and environment studies) to inform the design of
      approaches for synthesizing quasi-experimental evidence in health systems
      research. Ultimately, the aim of any review is practical: to provide useful
      information for policymakers, practitioners, and researchers. Future work should
      focus on building a consensus among users and producers of systematic reviews
      regarding the inclusion of quasi-experiments. 

PMID- 25776034
TI  - Managed care in four managed competition OECD health systems.
AB  - Managed care emerged in the American health system in the 1980s as a way to
      manage suppliers' induced demand and to contain insurers' costs. While in Israel
      the health insurers have always been managed care organizations, owning health
      care facilities, employing medical personnel or contracting selectively with
      independent providers, European insurers have been much more passive, submitting
      themselves to collective agreements between insurers' and providers'
      associations, accompanied by extensive government regulation of prices,
      quantities, and budgets. With the 1990s reforms, and the introduction of risk
      adjusted "managed competition", a growing pressure to allow the European insurers
      to manage their own care - including selective contracting with providers - has
      emerged, with varying speed of the introduction of policy changes across the
      individual countries. This paper compares experiences with managed care in
      Israel, The Netherlands, Germany and Switzerland since the 1990s. After a brief
      description of the health insurance markets in the four countries, we focus
      comparatively on the emergence of managed care in the markets for ambulatory care
      and inpatient market care. We conclude with an evaluation of the current
      situation and a discussion of selected health policy issues. 

PMID- 25776035
TI  - Use and Spending for Biologic Disease-Modifying Antirheumatic Drugs for
      Rheumatoid Arthritis Among US Medicare Beneficiaries.
AB  - OBJECTIVE: Biologic therapies have assumed an important role in treating
      rheumatoid arthritis (RA). We sought to investigate use, spending, and patient
      cost-sharing for Medicare beneficiaries using biologic drugs for RA, comparing
      patients exposed to minimal cost-sharing because of a Part D low-income subsidy
      (LIS) to those facing substantial out-of-pocket costs (OOP). METHODS: We
      performed a retrospective, nationwide study using 2009 Medicare claims for a 5%
      random sample of beneficiaries with RA who had at least 1 RA drug dispensed. We
      analyzed biologic drug utilization and costs across the Part B (medical benefit)
      and Part D (pharmacy benefit) programs by LIS status using multinomial
      regression. We also projected OOP costs as the Affordable Care Act (ACA) mandates
      closure of the Part D coverage gap by 2020. RESULTS: Among 6,932 beneficiaries,
      1,812 (26.1%) received a biologic drug. LIS beneficiaries were significantly more
      likely to obtain Part D home-administered biologics (relative risk ratio [RRR]
      2.98, 95% confidence interval [95% CI] 2.50-3.56), while non-LIS beneficiaries
      were less likely to receive Part D biologic agents (RRR 0.58, 95% CI 0.48-0.69).
      OOP costs in Part D were lower, as expected, for LIS beneficiaries ($72 versus
      $3,751 per year for non-LIS). Non-LIS beneficiaries had lower costs for Part B
      facility-administered biologic agents (range $0-$2,584) than for Part D home
      administered biologic agents. ACA reforms will narrow OOP differences between
      Part D and B for non-LIS beneficiaries. CONCLUSION: In contrast to LIS
      beneficiaries who receive mostly Part D home-administered biologic DMARDs,
      nonsubsidized beneficiaries have significant cost-based incentives to obtain
      facility-administered biologic DMARDs through Part B. The ACA will result in only
      slightly lower costs for Part D biologic drugs for these beneficiaries.

PMID- 25776036
TI  - The cytosolic sensor, DDX41, activates antiviral and inflammatory immunity in
      response to stimulation with double-stranded DNA adherent cells of the olive
      flounder, Paralichthys olivaceus.
AB  - DDX41, a receptor belonging to the DExD family, functions as a DNA sensor in the
      mammalian cytoplasm and mediates the antiviral response in host cells. Here, the
      olive flounder DDX41 was found to have 2267-bp long and encodes a putative
      protein of 614 amino acid residues. The olive flounder DDX41 mRNA was presented
      in all tested tissues, and was distinctly expressed in fish naturally infected
      with LCDV. High expression levels were observed in the heart, liver, kidney and
      stomach. Furthermore, the olive flounder DDX41 mRNA expression increased
      significantly in adherent (monocyte-like) cells following stimulation with a DNA
      virus. Reporter assays showed that the transcriptional activity of the IFN-I
      promoter was enhanced in DDX41-overexpressing HINAE cells treated with C-di-GMP
      (dinucleotides). Overexpression of DDX41 also induced the antiviral and
      inflammatory cytokine gene expression through cytoplasmic C-di-GMP treatment.
      These results suggest that DDX41 functions as a cytosolic DNA sensor that is
      capable of inducing antiviral activity and inflammatory responses in the olive
      flounder. 

PMID- 25776037
TI  - Effects of sleep deprivation and aging on long-term and remote memory in mice.
AB  - Sleep deprivation (SD) following hippocampus-dependent learning in young mice
      impairs memory when tested the following day. Here, we examined the effects of SD
      on remote memory in both young and aged mice. In young mice, we found that memory
      is still impaired 1 mo after training. SD also impaired memory in aged mice 1 d
      after training, but, by a month after training, sleep-deprived and control aged
      animals performed similarly, primarily due to remote memory decay in the control
      aged animals. Gene expression analysis supported the finding that SD has similar
      effects on the hippocampus in young and aged mice. 

PMID- 25776038
TI  - Cholinergic manipulations bidirectionally regulate object memory destabilization.
AB  - Consolidated memories can become destabilized and open to modification upon
      retrieval. Destabilization is most reliably prompted when novel information is
      present during memory reactivation. We hypothesized that the neurotransmitter
      acetylcholine (ACh) plays an important role in novelty-induced memory
      destabilization because of its established involvement in new learning.
      Accordingly, we investigated the effects of cholinergic manipulations in rats
      using an object recognition paradigm that requires reactivation novelty to
      destabilize object memories. The muscarinic receptor antagonist scopolamine,
      systemically or infused directly into the perirhinal cortex, blocked this novelty
      induced memory destabilization. Conversely, systemic oxotremorine or carbachol,
      muscarinic receptor agonists, administered systemically or intraperirhinally,
      respectively, mimicked the destabilizing effect of novel information during
      reactivation. These bidirectional effects suggest a crucial influence of ACh on
      memory destabilization and the updating functions of reconsolidation. This is a
      hitherto unappreciated mnemonic role for ACh with implications for its potential
      involvement in cognitive flexibility and the dynamic process of long-term memory
      storage.

PMID- 25776039
TI  - Impact of adolescent sucrose access on cognitive control, recognition memory, and
      parvalbumin immunoreactivity.
AB  - In this study we sought to determine the effect of daily sucrose consumption in
      young rats on their subsequent performance in tasks that involve the prefrontal
      cortex and hippocampus. High levels of sugar consumption have been associated
      with the development of obesity, however less is known about how sugar
      consumption influences behavioral control and high-order cognitive processes. Of
      particular concern is the fact that sugar intake is greatest in adolescence, an
      important neurodevelopmental period. We provided sucrose to rats when they were
      progressing through puberty and adolescence. Cognitive performance was assessed
      in adulthood on a task related to executive function, a rodent analog of the
      Stroop task. We found that sucrose-exposed rats failed to show context
      appropriate responding during incongruent stimulus compounds presented at test,
      indicative of impairments in prefrontal cortex function. Sucrose exposed rats
      also showed deficits in an on object-in-place recognition memory task, indicating
      that both prefrontal and hippocampal function was impaired. Analysis of brains
      showed a reduction in expression of parvalbumin-immunoreactive GABAergic
      interneurons in the hippocampus and prefrontal cortex, indicating that sucrose
      consumption during adolescence induced long-term pathology, potentially
      underpinning the cognitive deficits observed. These results suggest that
      consumption of high levels of sugar-sweetened beverages by adolescents may also
      impair neurocognitive functions affecting decision-making and memory, potentially
      rendering them at risk for developing mental health disorders.

PMID- 25776040
TI  - The Class I HDAC inhibitor RGFP963 enhances consolidation of cued fear
      extinction.
AB  - Evidence indicates that broad, nonspecific histone deacetylase (HDAC) inhibition
      enhances learning and memory, however, the contribution of the various HDACs to
      specific forms of learning is incompletely understood. Here, we show that the
      Class I HDAC inhibitor, RGFP963, enhances consolidation of cued fear extinction.
      However, RGFP966, a strong inhibitor of HDAC3, does not significantly enhance
      consolidation of cued fear extinction. These data extend previous evidence that
      demonstrate the Class I HDACs play a role in the consolidation of long-term
      memory, suggesting that HDAC1 and/or HDAC2, but less likely HDAC3, may function
      as negative regulators of extinction retention. The development of specific HDAC
      inhibitors, such as RGFP963, will further illuminate the role of specific HDACs
      in various types of learning and memory. Moreover, HDAC inhibitors that enhance
      cued fear extinction may show translational promise for the treatment of fear
      related disorders, including post-traumatic stress disorder (PTSD).

PMID- 25776041
TI  - 'Engage me in taking care of my heart': a grounded theory study on patient
      cardiologist relationship in the hospital management of heart failure.
AB  - OBJECTIVE: In approaching the study and practice of heart failure (HF)
      management, authors recognise that the patient-doctor relationship has a central
      role in engaging patients in their care. This study aims at identifying the
      features and the levers of HF patient engagement and suggestions for orienting
      clinical encounters. DESIGN: Using a grounded theory approach, we conducted 22 in
      depth interviews (13 patients with HF, 5 physicians and 4 caregivers). Data were
      collected and analysed using open, axial and selective coding procedures
      according to the grounded theory principles. SETTINGS: All interviews were
      conducted in an office in a university hospital located in a metropolitan area of
      Milan, Italy. PARTICIPANTS: The data comprised a total of 22 patient, hospital
      cardiologist and caregiver interviews. Patients aged >=18 years with New York
      Heart Association (NYHA) Functional Class of II or III were eligible to take
      part. Patients were recruited primarily through their referral cardiologist.
      RESULTS: The HF patient engagement process develops in four main phases that are
      characterised by different patients' emotional, cognitive and behavioural
      dynamics that contribute to shape the process of a patient's meaning making
      towards health and illness regarding their care. The emerging model illustrates
      that HF patient engagement entails a meaning-making process enacted by the
      patient after the critical event. This implies patients' ability to give sense to
      their care experience and to their disease, symptomatology and treatments, and
      their changes along their illness course. Doctors are recognised as crucial in
      fostering patients' engagement along all the phases of the process as they
      contribute to providing patients with self-continuity and give new meaning to
      their illness experience. CONCLUSIONS: This study identifies the core
      experiential domains and the main levers involved in driving patients with HF to
      effectively engage in their disease management. The model emerging from this
      study may help clinicians think in a fresh way about encounters with patients and
      their role in fostering their patients' health engagement.

PMID- 25776042
TI  - Overweight and obesity on the island of Ireland: an estimation of costs.
AB  - OBJECTIVES: The increasing prevalence of overweight and obesity worldwide
      continues to compromise population health and creates a wider societal cost in
      terms of productivity loss and premature mortality. Despite extensive
      international literature on the cost of overweight and obesity, findings are
      inconsistent between Europe and the USA, and particularly within Europe. Studies
      vary on issues of focus, specific costs and methods. This study aims to estimate
      the healthcare and productivity costs of overweight and obesity for the island of
      Ireland in 2009, using both top-down and bottom-up approaches. METHODS: Costs
      were estimated across four categories: healthcare utilisation, drug costs, work
      absenteeism and premature mortality. Healthcare costs were estimated using
      Population Attributable Fractions (PAFs). PAFs were applied to national cost data
      for hospital care and drug prescribing. PAFs were also applied to social welfare
      and national mortality data to estimate productivity costs due to absenteeism and
      premature mortality. RESULTS: The healthcare costs of overweight and obesity in
      2009 were estimated at ?437 million for the Republic of Ireland (ROI) and ?127.41
      million for NI. Productivity loss due to overweight and obesity was up to ?865
      million for ROI and ?362 million for NI. The main drivers of healthcare costs are
      cardiovascular disease, type II diabetes, colon cancer, stroke and gallbladder
      disease. In terms of absenteeism, low back pain is the main driver in both
      jurisdictions, and for productivity loss due to premature mortality the primary
      driver of cost is coronary heart disease. CONCLUSIONS: The costs are substantial,
      and urgent public health action is required in Ireland to address the problem of
      increasing prevalence of overweight and obesity, which if left unchecked will
      lead to unsustainable cost escalation within the health service and unacceptable
      societal costs.

PMID- 25776043
TI  - Prevalence, risk factors and associations of primary Raynaud's phenomenon:
      systematic review and meta-analysis of observational studies.
AB  - OBJECTIVE: To systematically review the literature with regard to the prevalence,
      incidence, risk factors and associations of primary Raynaud's phenomenon (PRP).
      METHOD: A systematic review of the literature of observational studies for PRP
      was undertaken using five electronic databases. Any studies reporting prevalence,
      incidence and risk factors of PRP were collected. Relative risk or OR and 95% CI
      were extracted or calculated to present the association between risk factors and
      PRP. Random effects model was used to pool the results. RESULTS: 33 articles
      assessing a total of 33,733 participants were included in this analysis (2
      cohort, 17 cross-sectional and 14 case-control studies). The pooled prevalence of
      PRP was 4.85% (95% CI 2.08% to 8.71%) in the general population. The pooled
      annual incidence of PRP was 0.25% (95% CI 0.19% to 0.32%). Risk factors and
      associations for PRP included female gender (OR=1.65, 95% CI 1.42 to 1.91),
      family history (OR=16.6, 95% CI 7.44 to 36.8), smoking (OR=1.27, 95% CI 1.06 to
      1.53), manual occupation (OR=2.66 95% CI 1.73 to 4.08), migraine (OR=4.02, 95% CI
      2.62 to 6.17), cardiovascular disease (OR=1.69, 95% CI 1.22 to 2.34) and marital
      status (married, OR=0.60, 95% CI 0.43 to 0.83). The definition of PRP varied
      considerably between studies. CONCLUSIONS: This is the first systematic review of
      the prevalence, incidence, risk factors and associations of PRP. Further study
      using uniform strict criteria for the condition is required to confirm these
      findings, particularly the possible association with cardiovascular disease.

PMID- 25776044
TI  - Pantethine Prevents Murine Systemic Sclerosis Through the Inhibition of
      Microparticle Shedding.
AB  - OBJECTIVE: Endothelial cell (EC) damage in systemic sclerosis (SSc) is reflected
      by the shedding of microparticles (MPs). The aim of this study was to show that
      inhibiting MP release using pantethine or by inactivating ATP-binding cassette
      transporter A1 (ABCA1) ameliorates murine SSc. METHODS: First, the effects of
      pantethine on MP shedding and on basal oxidative and nitrosative stresses in ECs
      and fibroblasts were determined in vitro. The effects of pantethine were then
      tested in vivo. SSc was induced in BALB/c mice by daily intradermal injection of
      HOCl. Mice were simultaneously treated daily with pantethine by oral gavage.
      RESULTS: In vitro, pantethine inhibited MP shedding from tumor necrosis factor
      stimulated ECs and abrogated MP-induced oxidative and nitrosative stresses in ECs
      and fibroblasts. Ex vivo, pantethine also restored redox homeostasis in
      fibroblasts from mice with SSc. In vivo, mice with SSc displayed skin and lung
      fibrosis associated with increased levels of circulating MPs and markers of
      oxidative and endothelial stress, which were normalized by administration of
      pantethine or inactivation of ABCA1. CONCLUSION: Pantethine is a well-tolerated
      molecule that represents a potential treatment of human SSc.

PMID- 25776045
TI  - SPEEDBOMB: a simple and rapid checklist for Prehospital Rapid Sequence Induction.
AB  - Prehospital emergency medical services often operate in the most challenging and
      austere environments. Checklist use for complex tasks in these circumstances is
      useful but must make task completion simpler, faster and more effective. The
      SPEEDBOMB checklist for Prehospital Rapid Sequence Induction (PRSI) management
      rapidly addresses critical steps in the RSI process, is designed to improve
      checklist compliance and patient safety, and is adaptable for local
      circumstances. 

PMID- 25776059
TI  - Significant performance enhancement of a UASB reactor by using acyl homoserine
      lactones to facilitate the long filaments of Methanosaeta harundinacea 6Ac.
AB  - Methanosaeta strains are frequently involved in the granule formation during
      methanogenic wastewater treatment. To investigate the impact of Methanosaeta on
      granulation and performance of upflow anaerobic sludge blanket (UASB) reactors,
      three 1-L working volume reactors noted as R1, R2, and R3 were operated fed with
      a synthetic wastewater containing sodium acetate and glucose. R1 was inoculated
      with 1-L activated sludge, while R2 and R3 were inoculated with 200-mL
      concentrated pre-grown Methanosaeta harundinacea 6Ac culture and 800 mL of
      activated sludge. Additionally, R3 was daily dosed with 0.5 mL/L of acetyl ether
      extract of 6Ac spent culture containing its quorum sensing signal carboxyl acyl
      homoserine lactone (AHL). Compared to R1, R2 and R3 had a higher and more
      constant chemical oxygen demand (COD) removal efficiency and alkaline pH (8.2)
      during the granulation phase, particularly, R3 maintained approximately 90 % COD
      removal. Moreover, R3 formed the best granules, and microscopic images showed
      fluorescent Methanosaeta-like filaments dominating in the R3 granules, but rod
      cells dominating in the R2 granules. Analysis of 16S rRNA gene libraries showed
      increased diversity of methanogen species like Methanosarcina and
      Methanospirillum in R2 and R3, and increased bacteria diversity in R3 that
      included the syntrophic propionate degrader Syntrophobacter. Quantitative PCR
      determined that 6Ac made up more than 22 % of the total prokaryotes in R3, but
      only 3.6 % in R2. The carboxyl AHL was detected in R3. This work indicates that
      AHL-facilitated filaments of Methanosaeta contribute to the granulation and
      performance of UASB reactors, likely through immobilizing other functional
      microorganisms. 

PMID- 25776060
TI  - Establishment of a functional secretory IgA transcytosis model system in vitro
      for functional food screening.
AB  - A characteristic mucosal immune response involves the production of antigen
      specific secretory immunoglobulin A (SIgA) antibodies. In order to study
      transcytosis by mimicking the SIgA secretion and to screen for SIgA secretion
      promoting substances, we developed a model system of a transfected Madin-Darby
      canine kidney (MDCK) cell line that expresses the human polymeric immunoglobulin
      receptor (pIgR). We thus isolated the human dIgA (dimeric IgA)/pIgA (polymeric
      IgA) complex as the binding ligands. In the present study, a recombinant vector
      encoding the human pIgR gene was constructed and infected into MDCK cells.
      Following reverse transcription polymerase chain reaction (RT-PCR),
      immunoblotting, and immunofluorescence staining, we confirmed that pIgR was
      expressed in the transfectant MDCK-pIgR cells and was located at the basolateral
      side of the cell surface. We also confirmed the coexistence of the dIgA/pIgA
      complex in the IgA myeloma serum. The covalent dIgA/pIgA complex was then
      isolated from the serum of an IgA multiple myeloma patient using an AKTA purifier
      operation system with a HiPrep 16/60 Sephacryl S-300 HR column, in order to
      utilize the complex as transcytosis ligands for human pIgR. Finally, we confirmed
      the uptake of the isolated human dIgA/pIgA complex into MDCK-pIgR cells. We
      demonstrated that the human dIgA/pIgA complex was transcytosed into the apical
      side of the monolayer cells. Therefore, our MDCK-human pIgR cell transcytosis
      model is an operational system and can be used for screening functional food
      components that promote dIgA/pIgR transcytosis as well as SIgA secretion. 

PMID- 25776061
TI  - Ribosomal protein biomarkers provide root nodule bacterial identification by
      MALDI-TOF MS.
AB  - Accurate identification of soil bacteria that form nitrogen-fixing associations
      with legume crops is challenging given the phylogenetic diversity of root nodule
      bacteria (RNB). The labor-intensive and time-consuming 16S ribosomal RNA (rRNA)
      sequencing and/or multilocus sequence analysis (MLSA) of conserved genes so far
      remain the favored molecular tools to characterize symbiotic bacteria. With the
      development of mass spectrometry (MS) as an alternative method to rapidly
      identify bacterial isolates, we recently showed that matrix-assisted laser
      desorption ionization (MALDI) time-of-flight (TOF) can accurately characterize
      RNB found inside plant nodules or grown in cultures. Here, we report on the
      development of a MALDI-TOF RNB-specific spectral database built on whole cell MS
      fingerprints of 116 strains representing the major rhizobial genera. In addition
      to this RNB-specific module, which was successfully tested on unknown field
      isolates, a subset of 13 ribosomal proteins extracted from genome data was found
      to be sufficient for the reliable identification of nodule isolates to rhizobial
      species as shown in the putatively ascribed ribosomal protein masses (PARPM)
      database. These results reveal that data gathered from genome sequences can be
      used to expand spectral libraries to aid the accurate identification of bacterial
      species by MALDI-TOF MS. 

PMID- 25776062
TI  - A novel approach to monitor stress-induced physiological responses in immobilized
      microorganisms.
AB  - Microbial cell immobilization has long been considered as a potential
      bioprocessing strategy to increase both microorganisms' tolerance and fitness in
      fermentation systems. To date, little emphasis has been put on how the entrapped
      cells respond to the bioprocessing stresses encountered during the cultivation.
      The present work presents for the first time a methodology to decipher the real
      health status of the entrapped microorganisms by combining multiparameter flow
      cytometry with confocal fluorescence microscopy as monitoring tools. Comparison
      between resting free and immobilized cell-based systems enabled to characterize
      the spatial-temporal physiological response of entrapped Pseudomonas taetrolens
      cells during lactobionic acid production in submerged cultivation. Whereas
      cellular leakage from beads led to planktonic cells that faced a progressive loss
      of membrane integrity, immobilized cells underwent a prompt stress-induced
      physiological response featured by the predominance of cellular damaging.
      Moreover, visualization without matrix de-entrapment through confocal
      fluorescence microscopy revealed the overtime formation of cellular micro
      colonies inside the beads. These micro-colonies comprised a shell made of dead
      cells, whereas the inward cells remained metabolically active. The proposed
      approach herein raises the possibility of using flow cytometry and confocal
      fluorescence microscopy as indicators of microbial cell immobilization, providing
      further key information on the health status and robustness of entrapped
      microorganisms. 

PMID- 25776063
TI  - Molecularly Imprinted Polymers as Tools for Bioassays and Biotransformation.
AB  - In the past five years, significant progress has been made in preparation of
      various molecularly imprinted polymer (MIP)-based materials for applications in
      bioassays and biotransformation. This chapter reviews the important advances in
      these two fields. The first part mainly focuses on the development of various MIP
      based bioassays that convert the rebinding of template to the imprinted cavities
      into measurable luminescent signals, including fluorescence, phosphorescence,
      Raman scattering, diffraction, and the like. In addition, MIP-based bioassays
      that are measured by surface plasmon resonance or quartz crystal microbalance are
      also discussed. In the following part, representative biotransformation reactions
      that make use of MIPs are summarized. In the last part of this chapter, some
      remaining challenges are briefly discussed for further development of the two
      fields.

PMID- 25776064
TI  - A new system of microwave ablation at 2450 MHz: preliminary experience.
AB  - The aim of this study was to assess the feasibility of the application of the new
      system (Emprint Microwave Ablation System, Covidien Boulder, CO, USA) and to
      identify its advantages. In particular the attention was focused to the spherical
      ablation zone obtained and its usefulness in terms of effectiveness. The new
      system is composed of: a 2450 MHz generator that delivers a maximum power of 100
      W, a fiberglass antenna and a pump for internally cooled antenna. Ten liver
      nodules (8 hepatocellular carcinomas and 2 metastasis) were percutaneously
      treated (mean diameter 24.9 mm, range 16-35 mm). Technical success, ablation
      duration time, overall procedure time and safety were registered. To define the
      shape of the ablation zone, multiplanar reformatting (MPR) was performed.
      Roundness index transverse was calculated: a value near 1 represents a more
      spherical ablation zone shape, and a value distant from 1 implies an oval
      configuration. Technical success was 100%. Mean ablation time was of 3.85 min
      (range 3-5 min), mean overall procedure time was 30.5 min (range 25-40 min). No
      major complications were recorded. Roundness index transverse presented a mean
      value of 0.94, meaning that a spherical shape of ablation zone was achieved. One
      of the most promising innovations of the new microwave technology is the
      spherical shape of the ablation volume that could be related with an improving of
      the effectiveness and safety.

PMID- 25776065
TI  - Non-contact, ultrasound-based indentation method for measuring elastic properties
      of biological tissues using harmonic motion imaging (HMI).
AB  - Noninvasive measurement of mechanical properties of biological tissues in vivo
      could play a significant role in improving the current understanding of tissue
      biomechanics. In this study, we propose a method for measuring elastic properties
      non-invasively by using internal indentation as generated by harmonic motion
      imaging (HMI). In HMI, an oscillating acoustic radiation force is produced by a
      focused ultrasound transducer at the focal region, and the resulting
      displacements are estimated by tracking radiofrequency signals acquired by an
      imaging transducer. In this study, the focal spot region was modeled as a rigid
      cylindrical piston that exerts an oscillatory, uniform internal force to the
      underlying tissue. The HMI elastic modulus EHMI was defined as the ratio of the
      applied force to the axial strain measured by 1D ultrasound imaging. The accuracy
      and the precision of the EHMI estimate were assessed both numerically and
      experimentally in polyacrylamide tissue-mimicking phantoms. Initial feasibility
      of this method in soft tissues was also shown in canine liver specimens in vitro.
      Very good correlation and agreement was found between the measured Young's
      modulus and the HMI modulus in the numerical study (r(2) > 0.99, relative error
      <10%) and on polyacrylamide gels (r(2) = 0.95, relative error <24%). The average
      HMI modulus on five liver samples was found to EHMI = 2.62  +/-  0.41 kPa,
      compared to EMechTesting = 4.2  +/-  2.58 kPa measured by rheometry. This study
      has demonstrated for the first time the initial feasibility of a non-invasive,
      model-independent method to estimate local elastic properties of biological
      tissues at a submillimeter scale using an internal indentation-like approach.
      Ongoing studies include in vitro experiments in a larger number of samples and
      feasibility testing in in vivo models as well as pathological human specimens. 

PMID- 25776066
TI  - Investigating the airborne transmission pathway - different approaches with the
      same objectives.

PMID- 25776067
TI  - Optimised empiric triple and concomitant therapy for Helicobacter pylori
      eradication in clinical practice: the OPTRICON study.
AB  - BACKGROUND: Empiric triple therapy for Helicobacter pylori should be abandoned
      when clarithromycin resistance rate is >15-20%. Optimisation of triple therapy
      (high-dose acid suppression and 14-day duration) can increase eradication rates
      by 10%. AIM: To compare the efficacy and safety of optimised triple (OPT-TRI) and
      nonbismuth quadruple concomitant (OPT-CON) therapies. METHODS: Prospective
      multicentre study in 16 Spanish centres using triple therapy in clinical
      practice. In a 3-month two-phase fashion, the first 402 patients received an OPT
      TRI therapy [esomeprazole (40 mg b.d.), amoxicillin (1 g b.d) and clarithromycin
      (500 mg b.d) for 14 days] and the last 375 patients an OPT-CON treatment [OPT-TRI
      therapy plus metronidazole (500 mg b.d)]. RESULTS: Seven-hundred seventy-seven
      consecutive patients were included (402 OPT-TRI, 375 OPT-CON). The OPT-CON
      therapy achieved significantly higher eradication rates in the per-protocol
      [82.3% (95% CI = 78-86%) vs. 93.8% (91-96%), P < 0.001] and intention-to-treat
      analysis [81.3% (78-86%) vs. 90.4% (87-93%), P < 0.001]. Adverse events (97%
      mild/moderate) were significantly more common with OPT-CON therapy (39% vs. 47%,
      P = 0.016), but full compliance with therapy was similar between groups (94% vs.
      92%, P = 0.4). OPT-CON therapy was the only significant predictor of successful
      eradication (odds ratio, 2.24; 95% CI: 1.48-3.51, P < 0.001). The rate of
      participating centres achieving cure rates >= 90% favoured OPT-CON therapy (OPT
      TRI 25% vs. OPT-CON 62%). CONCLUSIONS: Empiric OPT-CON therapy achieved
      significantly higher cure rates (>90%) compared to OPT-TRI therapy. Addition of
      metronidazole to OPT-TRI therapy increased eradication rates by 10%, resulting in
      more mild adverse effects, but without impairing compliance with therapy.

PMID- 25776068
TI  - Newly stemming functions of macula densa-derived prostanoids.

PMID- 25776069
TI  - Mutation of SH2B3 (LNK), a genome-wide association study candidate for
      hypertension, attenuates Dahl salt-sensitive hypertension via inflammatory
      modulation.
AB  - Human genome-wide association studies have linked SH2B adaptor protein 3 (SH2B3,
      LNK) to hypertension and renal disease, although little experimental
      investigation has been performed to verify a role for SH2B3 in these pathologies.
      SH2B3, a member of the SH2B adaptor protein family, is an intracellular adaptor
      protein that functions as a negative regulator in many signaling pathways,
      including inflammatory signaling processes. To explore a mechanistic link between
      SH2B3 and hypertension, we targeted the SH2B3 gene for mutation on the Dahl salt
      sensitive (SS) rat genetic background with zinc-finger nucleases. The resulting
      mutation was a 6-bp, in-frame deletion within a highly conserved region of the
      Src homology 2 (SH2) domain of SH2B3. This mutation significantly attenuated Dahl
      SS hypertension and renal disease. Also, infiltration of leukocytes into the
      kidneys, a key mediator of Dahl SS pathology, was significantly blunted in the
      Sh2b3(em1Mcwi) mutant rats. To determine whether this was because of differences
      in immune signaling, bone marrow transplant studies were performed in which Dahl
      SS and Sh2b3(em1Mcwi) mutants underwent total body irradiation and were then
      transplanted with Dahl SS or Sh2b3(em1Mcwi) mutant bone marrow. Rats that
      received Sh2b3(em1Mcwi) mutant bone marrow had a significant reduction in mean
      arterial pressure and kidney injury when placed on a high salt diet (4% NaCl).
      These data further support a role for the immune system as a modulator of disease
      severity in the pathogenesis of hypertension and provide insight into
      inflammatory mechanisms at play in human hypertension and renal disease. 

PMID- 25776070
TI  - Proinflammatory cytokines upregulate sympathoexcitatory mechanisms in the
      subfornical organ of the rat.
AB  - Our previous work indicated that the subfornical organ (SFO) is an important
      brain sensor of blood-borne proinflammatory cytokines, mediating their central
      effects on autonomic and cardiovascular function. However, the mechanisms by
      which SFO mediates the central effects of circulating proinflammatory cytokines
      remain unclear. We hypothesized that proinflammatory cytokines act within the SFO
      to upregulate the expression of excitatory and inflammatory mediators that drive
      sympathetic nerve activity. In urethane-anesthetized Sprague-Dawley rats, direct
      microinjection of tumor necrosis factor (TNF)-alpha (25 ng) or interleukin (IL)
      1beta (25 ng) into SFO increased mean blood pressure, heart rate, and renal
      sympathetic nerve activity within 15 to 20 minutes, mimicking the response to
      systemically administered proinflammatory cytokines. Pretreatment of SFO with
      microinjections of the angiotensin II type-1 receptor blocker losartan (1 MUg),
      angiotensin-converting enzyme inhibitor captopril (1 MUg) or cyclooxygenase-2
      inhibitor NS-398 (2 MUg) attenuated those responses. Four hours after the SFO
      microinjection of TNF-alpha (25 ng) or IL-1beta (25 ng), mRNA for angiotensin
      converting enzyme, angiotensin II type-1 receptor, TNF-alpha and the p55 TNF
      alpha receptor, IL-1beta and the IL-1R receptor, and cyclooxygenase-2 had
      increased in SFO, and mRNA for angiotensin-converting enzyme, angiotensin II type
      1 receptor, and cyclooxygenase-2 had increased downstream in the hypothalamic
      paraventricular nucleus. Confocal immunofluorescent images revealed that
      immunoreactivity for the p55 TNF-alpha receptor and the IL-1 receptor accessory
      protein, a subunit of the IL-1 receptor, colocalized with angiotensin-converting
      enzyme, angiotensin II type-1 receptor-like, cyclooxygenase-2, and prostaglandin
      E2 EP3 receptor immunoreactivity in SFO neurons. These data suggest that
      proinflammatory cytokines act within the SFO to upregulate the expression of
      inflammatory and excitatory mediators that drive sympathetic excitation. 

PMID- 25776071
TI  - DACH1, a zona glomerulosa selective gene in the human adrenal, activates
      transforming growth factor-beta signaling and suppresses aldosterone secretion.
AB  - Common somatic mutations in CACNAID and ATP1A1 may define a subgroup of smaller,
      zona glomerulosa (ZG)-like aldosterone-producing adenomas. We have therefore
      sought signature ZG genes, which may provide insight into the frequency and
      pathogenesis of ZG-like aldosterone-producing adenomas. Twenty-one pairs of zona
      fasciculata and ZG and 14 paired aldosterone-producing adenomas from 14 patients
      with Conn's syndrome and 7 patients with pheochromocytoma were assayed by the
      Affymetrix Human Genome U133 Plus 2.0 Array. Validation by quantitative real-time
      polymerase chain reaction was performed on genes >10-fold upregulated in ZG
      (compared with zona fasciculata) and >10-fold upregulated in aldosterone
      producing adenomas (compared with ZG). DACH1, a gene associated with tumor
      progression, was further analyzed. The role of DACH1 on steroidogenesis,
      transforming growth factor-beta, and Wnt signaling activity was assessed in the
      human adrenocortical cell line, H295R. Immunohistochemistry confirmed selective
      expression of DACH1 in human ZG. Silencing of DACH1 in H295R cells increased
      CYP11B2 mRNA levels and aldosterone production, whereas overexpression of DACH1
      decreased aldosterone production. Overexpression of DACH1 in H295R cells
      activated the transforming growth factor-beta and canonical Wnt signaling
      pathways but inhibited the noncanonical Wnt signaling pathway. Stimulation of
      primary human adrenal cells with angiotensin II decreased DACH1 mRNA expression.
      Interestingly, there was little overlap between our top ZG genes and those in
      rodent ZG. In conclusion, (1) the transcriptome profile of human ZG differs from
      rodent ZG, (2) DACH1 inhibits aldosterone secretion in human adrenals, and (3)
      transforming growth factor-beta signaling pathway is activated in DACH1
      overexpressed cells and may mediate inhibition of aldosterone secretion in human
      adrenals.

PMID- 25776072
TI  - SH2B3 (LNK) as a novel link of immune signaling, inflammation, and hypertension
      in Dahl salt-sensitive hypertensive rats.

PMID- 25776073
TI  - Cardiovascular magnetic resonance for early atherosclerosis detection: fiction or
      reality?

PMID- 25776074
TI  - Measurement of peripheral plasma 18-oxocortisol can discriminate unilateral
      adenoma from bilateral diseases in patients with primary aldosteronism.
AB  - Adrenal venous sampling is currently the only reliable method to distinguish
      unilateral from bilateral diseases in primary aldosteronism. In this study, we
      attempted to determine whether peripheral plasma levels of 18-oxocortisol
      (18oxoF) and 18-hydroxycortisol could contribute to the clinical differentiation
      between aldosteronoma and bilateral hyperaldosteronism in 234 patients with
      primary aldosteronism, including computed tomography (CT)-detectable
      aldosteronoma (n=113) and bilateral hyperaldosteronism (n=121), all of whom
      underwent CT and adrenal venous sampling. All aldosteronomas were surgically
      resected and the accuracy of diagnosis was clinically and histopathologically
      confirmed. 18oxoF and 18-hydroxycortisol were measured using liquid
      chromatography tandem mass spectrometry. Receiver operating characteristic
      analysis of 18oxoF discrimination of adenoma from hyperplasia demonstrated
      sensitivity/specificity of 0.83/0.99 at a cut-off value of 4.7 ng/dL, compared
      with that based on 18-hydroxycortisol (sensitivity/specificity: 0.62/0.96).
      18oxoF levels above 6.1 ng/dL or of aldosterone >32.7 ng/dL were found in 95 of
      113 patients with aldosteronoma (84%) but in none of 121 bilateral
      hyperaldosteronism, 30 of whom harbored CT-detectable unilateral nonfunctioning
      nodules in their adrenals. In addition, 18oxoF levels below 1.2 ng/dL, the lowest
      in aldosteronoma, were found 52 of the 121 (43%) patients with bilateral
      hyperaldosteronism. Further analysis of 27 patients with CT-undetectable micro
      aldosteronomas revealed that 8 of these 27 patients had CT-detectable
      contralateral adrenal nodules, the highest values of 18oxoF and aldosterone were
      4.8 and 24.5 ng/dL, respectively, both below their cut-off levels indicated
      above. The peripheral plasma 18oxoF concentrations served not only to
      differentiate aldosteronoma but also could serve to avoid unnecessary surgery for
      nonfunctioning adrenocortical nodules concurrent with hyperplasia or
      microadenoma.

PMID- 25776075
TI  - Salt restriction leads to activation of adult renal mesenchymal stromal cell-like
      cells via prostaglandin E2 and E-prostanoid receptor 4.
AB  - Despite the importance of juxtaglomerular cell recruitment in the pathophysiology
      of cardiovascular diseases, the mechanisms that underlie renin production under
      conditions of chronic stimulation remain elusive. We have previously shown that
      CD44+ mesenchymal-like cells (CD44+ cells) exist in the adult kidney. Under
      chronic sodium deprivation, these cells are recruited to the juxtaglomerular area
      and differentiate to new renin-expressing cells. Given the proximity of macula
      densa to the juxtaglomerular area and the importance of macula densa released
      prostanoids in renin synthesis and release, we hypothesized that chronic sodium
      deprivation induces macula densa release of prostanoids, stimulating renal CD44+
      cell activation and differentiation. CD44+ cells were isolated from adult kidneys
      and cocultured with the macula densa cell line, MMDD1, in normal or low-sodium
      medium. Low sodium stimulated prostaglandin E2 production by MMDD1 and induced
      migration of CD44+ cells. These effects were inhibited by addition of a
      cyclooxygenase 2 inhibitor (NS398) or an E-prostanoid receptor 4 antagonist
      (AH23848) to MMDD1 or CD44+ cells, respectively. Addition of prostaglandin E2 to
      CD44+ cells increased cell migration and induced renin expression. In vivo
      activation of renal CD44+ cells during juxtaglomerular recruitment was attenuated
      in wild-type mice subjected to salt restriction in the presence of cyclooxygenase
      2 inhibitor rofecoxib. Similar results were observed in E-prostanoid receptor 4
      knockout mice subjected to salt restriction. These results show that the
      prostaglandin E2/E-prostanoid receptor 4 pathway plays a key role in the
      activation of renal CD44+ mesenchymal stromal cell-like cells during conditions
      of juxtaglomerular recruitment; highlighting the importance of this pathway as a
      key regulatory mechanism of juxtaglomerular recruitment. 

PMID- 25776076
TI  - Discordant orthostatic reflex renin-angiotensin and sympathoneural responses in
      premenopausal exercising-hypoestrogenic women.
AB  - Our prior observations in normotensive postmenopausal women stimulated the
      hypotheses that compared with eumenorrheic women, active hypoestrogenic
      premenopausal women with functional hypothalamic amenorrhea would demonstrate
      attenuated reflex renin-angiotensin-aldosterone system responses to an
      orthostatic challenge, whereas to defend blood pressure reflex increases in
      muscle, sympathetic nerve activity would be augmented. To test these hypotheses,
      we assessed, in recreationally active women, 12 with amenorrhea (ExFHA; aged 25
      +/- 1 years; body mass index 20.7 +/- 0.7 kg/m(2); mean +/- SEM) and 17 with
      eumenorrhea (ExOv; 24 +/- 1 years; 20.9 +/- 0.5 kg/m(2)), blood pressure, heart
      rate, plasma renin, angiotensin II, aldosterone, and muscle sympathetic nerve
      activity at supine rest and during graded lower body negative pressure (-10, -20,
      and -40 mm Hg). At baseline, heart rate and systolic blood pressure were lower
      (P<0.05) in ExFHA (47 +/- 2 beats/min and 94 +/- 2 mm Hg) compared with ExOv (56
      +/- 2 beats/min and 105 +/- 2 mm Hg), but muscle sympathetic nerve activity and
      renin-angiotensin-aldosterone system constituents were similar (P>0.05). In
      response to graded lower body negative pressure, heart rate increased (P<0.05)
      and systolic blood pressure decreased (P<0.05) in both groups, but these remained
      consistently lower in ExFHA (P<0.05). Lower body negative pressure elicited
      increases (P<0.05) in renin, angiotensin II, and aldosterone in ExOv, but not in
      ExFHA (P>0.05). Muscle sympathetic nerve activity burst incidence increased
      reflexively in both groups, but more so in ExFHA (P<0.05). Otherwise, healthy
      hypoestrogenic ExFHA women demonstrate low blood pressure and disruption of the
      normal circulatory response to an orthostatic challenge: plasma renin,
      angiotensin II, and aldosterone fail to increase and blood pressure is defended
      by an augmented sympathetic vasoconstrictor response.

PMID- 25776077
TI  - AT2R agonist, compound 21, is reno-protective against type 1 diabetic
      nephropathy.
AB  - The hemodynamic and nonhemodynamic effects of angiotensin II on diabetic
      complications are considered to be primarily mediated by the angiotensin II type
      1 receptor subtype. However, its biological and functional effect mediated
      through the angiotensin II type 2 receptor subtype is still unclear. Activation
      of the angiotensin II type 2 receptors has been postulated to oppose angiotensin
      II type 1 receptor-mediated actions and thus attenuate fibrosis. This study aimed
      to elucidate the reno-protective role of the novel selective angiotensin II type
      2 receptor agonist, Compound 21, in an experimental model of type 1 diabetic
      nephropathy. Compound 21 treatment significantly attenuated diabetes mellitus
      induced elevated levels of cystatin C, albuminuria, mesangial expansion, and
      glomerulosclerosis in diabetic mice. Moreover, Compound 21 markedly inhibited the
      expression of various proteins implicated in oxidative stress, inflammation, and
      fibrosis, in association with decreased extracellular matrix production. These
      findings demonstrate that monotherapy of Compound 21 is protective against the
      progression of experimental diabetic nephropathy by inhibiting renal oxidative
      stress, inflammation, and fibrosis. 

PMID- 25776078
TI  - Evolution of aortic wall thickness and stiffness with atherosclerosis: long-term
      follow up from the multi-ethnic study of atherosclerosis.
AB  - The study was performed to determine age, sex, and time-dependent changes in
      aortic wall thickness (AWT) and to evaluate cross-sectional associations between
      AWT and arterial stiffness in older adults. Three hundred seventy-one
      longitudinal and 426 cross-sectional measurements of AWT from cardiovascular
      magnetic resonance imaging studies conducted within the Multi-Ethnic Study of
      Atherosclerosis were analyzed at 2 points in time, in 2000 to 2002 and then again
      from follow-up examinations in 2010 to 2012. Aortic wall thickness was determined
      from a double inversion recovery black-blood fast spin-echo sequence, and aortic
      stiffness was measured from a phase-contrast cine gradient echo sequence. The
      thickness of the midthoracic descending aortic wall was measured and correlated
      to distensibility of the ascending aorta and aortic pulse wave velocity. The
      average rate of AWT change was 0.032 mm/y. The increase in AWT was greater for
      those aged 45 to 54 years relative to individuals older than 55 years (P
      trend<0.001). Ascending aortic distensibility was lower (P<0.001) and pulse wave
      velocity was higher (P=0.012) for hypertensive subjects. After adjustment for
      traditional risk factors, distensibility of the ascending aorta was significantly
      related to AWT in participants without hypertension. Hypertension was associated
      with increased aortic stiffness independent of aortic wall thickness. 

PMID- 25776079
TI  - Implication of microRNA regulation in para-phenylenediamine-induced cell death
      and senescence in normal human hair dermal papilla cells.
AB  - Para-phenylenediamine (PPD) is a major component of hair coloring and black henna
      products. Although it has been largely demonstrated that PPD induces allergic
      reactions and increases the risk of tumors in the kidney, liver, thyroid gland
      and urinary bladder, the effect on dermal papilla cells remains to be elucidated.
      Therefore, the current study evaluated the effects of PPD on growth, cell death
      and senescence using cell-based assays and microRNA (miRNA) microarray in normal
      human hair dermal papilla cells (nHHDPCs). Cell viability and cell cycle analyses
      demonstrated that PPD exhibited a significant cytotoxic effect on nHHDPCs through
      inducing cell death and G2 phase cell cycle arrest in a dose-dependent manner. It
      was additionally observed that treatment of nHHDPCs with PPD induced cellular
      senescence by promoting cellular oxidative stress. In addition, the results of
      the current study indicated that these PPD-mediated effects were involved in the
      alteration of miRNA expression profiles. Treatment of nHHDPCs with PPD altered
      the expression levels of 74 miRNAs by >= 2-fold (16 upregulated and 58
      downregulated miRNAs). Further bioinformatics analysis determined that these
      identified miRNA target genes were likely to be involved in cell growth, cell
      cycle arrest, cell death, senescence and the induction of oxidative stress. In
      conclusion, the observations of the current study suggested that PPD was able to
      induce several cytotoxic effects through alteration of miRNA expression levels in
      nHHDPCs.

PMID- 25776080
TI  - Human cytomegalovirus riding the cell cycle.
AB  - Human cytomegalovirus (HCMV) infection modulates the host cell cycle to create an
      environment that is optimal for viral gene expression, DNA replication, and
      production of infectious virus. The virus mostly infects quiescent cells and thus
      must push the cell into G1 phase of the cell cycle to co-opt the cellular
      mechanisms that could be used for DNA synthesis. However, at the same time,
      cellular functions must be subverted such that synthesis of viral DNA is favored
      over that of the host. The molecular mechanisms by which this is accomplished
      include altered RNA transcription, changes in the levels and activity of cyclin
      dependent kinases, and other proteins involved in cell cycle control,
      posttranslational modifications of proteins, modulation of protein stability
      through targeted effects on the ubiquitin-proteasome degradation pathway, and
      movement of proteins to different cellular locations. When the cell is in the
      optimal G0/G1 phase, multiple signaling pathways are altered to allow rapid
      induction of viral gene expression once negative factors have been eliminated.
      For the most part, the cell cycle will stop prior to initiation of host cell DNA
      synthesis (S phase), although many cell cycle proteins characteristic of the
      S/G2/M phase accumulate. The environment of a cell progressing through the cell
      cycle and dividing is not favorable for viral replication, and HCMV has evolved
      ways to sense whether cells are in S/G2 phase, and if so, to prevent initiation
      of viral gene expression until the cells cycle back to G1. A major target of HCMV
      is the anaphase-promoting complex E3 ubiquitin ligase, which is responsible for
      the ubiquitination and subsequent degradation of cyclins A and B and other cell
      cycle proteins at specific phases in the cell cycle. This review will discuss the
      effects of HCMV infection on cell cycle regulatory pathways, with the focus on
      selected viral proteins that are responsible for these effects. 

PMID- 25776098
TI  - Neuralgic amyotrophy associated with temporary vocal fold paralysis: successful
      treatment by vocal fold augmentation with hyaluronic acid.
AB  - BACKGROUND: Neuralgic amyotrophy is a polyneuropathy that classically involves
      the brachial plexus. This paper reports an unusual clinical manifestation
      associated with vocal fold paralysis. CASE REPORT: A 36-year-old male presented
      with hoarseness and progressive weakness of the right shoulder and upper arm
      muscles. Laryngoscopy revealed a limited adduction of the right vocal fold.
      RESULTS: Subsequent speech therapy did not improve the symptoms. Therefore, vocal
      fold augmentation by application of hyaluronic acid in the right vocal fold was
      performed. CONCLUSION: Vocal fold augmentation with resorbable material seems to
      be a more effective transient treatment than speech therapy alone for patients
      with neuralgic amyotrophy and laryngeal involvement.

PMID- 25776099
TI  - Design of a novel type IV lipid-based delivery system for improved delivery of
      drugs with low partition coefficient.
AB  - CONTEXT: The physicochemical properties of drugs such as partition coefficient
      play a major role in the development of lipid-based drug delivery systems. The
      major obstacle lies in encapsulation of a drug with low partition coefficient
      into these systems. OBJECTIVE: The objective of this study was to design and
      optimize a novel lipid-based delivery system with higher loading, improved
      pharmacokinetics consequently enhancing the oral bioavailability of drugs with
      low partition coefficient like valsartan. MATERIALS AND METHODS: The optimized
      formulation consists of Capryol 90, Cremophor RH 40, and Transcutol HP. Pseudo
      ternary phase diagrams were used to optimize the components and their
      concentrations in the formulation. Dissolution studies of the selected
      formulations were compared with plain drug and marketed product at three pH
      conditions (pH 1.2, 4.5 and 6.8). Pharmacokinetic parameters of optimized
      formulations were determined in Wistar rats and compared with that of plain drug.
      RESULTS AND DISCUSSION: The optimized formulation with a mean particle size of 50
      nm showed significant improvement (p < 0.05) in dissolution rate with pH
      independence compared to plain drug and marketed product. The in vivo studies in
      Wistar rats revealed about 2.30- and 1.68-fold increase in the oral
      bioavailability and Cmax of valsartan from lipid-based formulation compared to
      plain drug. CONCLUSION: The engineered formulation strategy by type IV lipid
      based formulations can be successfully exploited to improve the dissolution rate
      and oral deliverability of drugs like valsartan.

PMID- 25776100
TI  - Tuberous Sclerosis Complex: An Update for Dermatologists.
AB  - Tuberous sclerosis complex is an autosomal dominant disorder that often manifests
      early in life with cutaneous features, and it is important that dermatologists
      who care for children remain up to date on its diagnosis and management. This
      article provides an update regarding the most recent guidelines for diagnosis
      published by the International Tuberous Sclerosis Complex Consensus Conference,
      which took place in 2012, and provides a brief literature review of the most
      recent developments in the treatment of skin findings. 

PMID- 25776081
TI  - Cytomegalovirus immune evasion of myeloid lineage cells.
AB  - Cytomegalovirus (CMV) evades the immune system in many different ways, allowing
      the virus to grow and its progeny to spread in the face of an adverse
      environment. Mounting evidence about the antiviral role of myeloid immune cells
      has prompted the research of CMV immune evasion mechanisms targeting these cells.
      Several cells of the myeloid lineage, such as monocytes, dendritic cells and
      macrophages, play a role in viral control, but are also permissive for CMV and
      are naturally infected by it. Therefore, CMV evasion of myeloid cells involves
      mechanisms that qualitatively differ from the evasion of non-CMV-permissive
      immune cells of the lymphoid lineage. The evasion of myeloid cells includes
      effects in cis, where the virus modulates the immune signaling pathways within
      the infected myeloid cell, and those in trans, where the virus affects somatic
      cells targeted by cytokines released from myeloid cells. This review presents an
      overview of CMV strategies to modulate and evade the antiviral activity of
      myeloid cells in cis and in trans. 

PMID- 25776101
TI  - Inhibitors for cholesterol ester accumulation in macrophages from Chinese
      cabbage.
AB  - The cholesterol ester accumulates in macrophages in the early stage of
      atherosclerotic lesions, leading to the formation of foam cells. We examined the
      inhibitory effects of the crude extracts of 22 edible plants on foam cell
      formation and isolated nine chlorophyll derivatives as potent inhibitors from
      Chinese cabbage. The results of the present study suggest that the chlorophyll
      derivatives contained in edible plants may be useful for the prevention and
      treatment of atherosclerosis. 

PMID- 25776102
TI  - Social differences in oral health: Dental status of individuals buried in and
      around Trakai Church in Lithuania (16th-17th c.c.).
AB  - The evaluation of social differences in dental health is based on the assumption
      that individuals belonging to a higher social class consumed a different diet
      than a common people. The aim of our study was to analyse and compare dental
      health of 16(th) - 17(th) c. individuals, buried inside and around the Roman
      Catholic Church in Trakai (Lithuania). All material (189 adult individuals) was
      divided in two samples of a presumably different social status: the Churchyard
      (ordinary townsmen) and the Presbytery (elite). Dental status analysis included
      that of tooth loss, tooth wear, caries, abscesses and calculus. Results revealed
      higher prevalence of dental disease in the Churchyard sample compared to the
      Presbytery. Individuals buried around the church had statistically higher
      prevalence of caries, antemortem tooth loss and abscesses compared to those who
      were buried inside the church. The Churchyard sample was also characterised by a
      higher increase in severity of caries with age, and a more rapid tooth wear.
      Differences in dental health between the samples the most probably reflect
      different dietary habits of people from different social groups: poor quality
      carbohydrate based diet of laymen buried in the churchyard and more varied diet
      with proteins and of a better quality of local elite, buried inside the church.
      Substantial sex differences in dental health were found only in the Churchyard
      sample: males had statistically higher prevalence of abscesses and calculus,
      while females had higher prevalence of caries and AMTL (antemortem tooth loss).
      Females were also characterised by a higher increase in the number of dental
      decay and tooth loss with age and had higher prevalence of gross caries, which
      indicates a more rapid progression of the disease. Worse dental health of females
      could be a result of culturally based dietary differences between females (more
      carbohydrates) and males (more proteins) and different physiological demands
      (hormonal fluctuations and suppression of immune system during pregnancy). 

PMID- 25776103
TI  - Self-template-directed synthesis of porous perovskite nanowires at room
      temperature for high-performance visible-light photodetectors.
AB  - The unique optoelectronic properties and promising photovoltaic applications of
      organolead halide perovskites have driven the exploration of facile strategies to
      synthesize organometal halide perovskites and corresponding hybrid materials and
      devices. Currently, the preparation of CH3 NH3 PbBr3 perovskite nanowires,
      especially those with porous features, is still a great challenge. An efficient
      self-template-directed synthesis of high-quality porous CH3 NH3 PbBr3 perovskite
      nanowires in solution at room temperature using the Pb-containing precursor
      nanowires as both the sacrificial template and the Pb(2+) source in the presence
      of CH3 NH3 Br and HBr is now presented. The initial formation of CH3 NH3 PbBr3
      perovskite layers on the surface of the precursor nanowires and the following
      dissolution of the organic component of the latter led to the formation of
      mesopores and the preservation of the 1D morphology. Furthermore, the perovskite
      nanowires are potential materials for visible-light photodetectors with high
      sensitivity and stability. 

PMID- 25776104
TI  - Effects of fucoidan on proliferation, AMP-activated protein kinase, and
      downstream metabolism- and cell cycle-associated molecules in poorly
      differentiated human hepatoma HLF cells.
AB  - Survival rates are low in patients with poorly differentiated hepatocellular
      carcinoma (HCC). Fucoidan, a sulfated polysaccharide derived from brown seaweed,
      has anticancer activity; however, the effects of fucoidan on poorly
      differentiated HCC remain unclear. In this study, we investigated the effects of
      fucoidan on AMP-activated protein kinase (AMPK), a proliferation regulator, and
      its downstream metabolism- and cell cycle-related molecules in a poorly
      differentiated human hepatoma HLF cell line. HLF cells were treated with fucoidan
      (10, 50, or 100 ug/ml; n=4) or phosphate buffered saline (control; n=4) for 96 h.
      Proliferation was evaluated by counting cells every 24 h. AMPK, TSC2, mTOR,
      GSK3beta, acetyl-CoA carboxylase (ACC), ATP-citrate lyase, p53, cyclin D1, cyclin
      dependent kinase (CDK) 4, and CDK6 expression and/or phosphorylation were
      examined by immunoblotting 24 h after treatment with 100 ug/ml fucoidan. Cell
      cycle progression was analyzed by fluorescence-activated cell sorter 48 h after
      treatment. Treatment with 50 or 100 ug/ml fucoidan significantly and dose- and
      time-dependently suppressed HLF cell proliferation (P<0.0001). Fucoidan induced
      AMPK phosphorylation on Ser172 24 h after treatment. Although no differences were
      seen in expression and phosphorylation levels of TSC2, mTOR, GSK3beta, ATP
      citrate lyase, and p53 between the control and fucoidan-treated HLF cells,
      fucoidan induced ACC phosphorylation on Ser79. Moreover, fucoidan decreased
      cyclin D1, CDK4 and CDK6 expression 24 h after treatment. Furthermore, HLF cells
      were arrested in the G1/S phase 48 h after fucoidan treatment. We demonstrated
      that fucoidan suppressed HLF cell proliferation with AMPK phosphorylation. We
      showed that fucoidan phosphorylated ACC and downregulated cyclin D1, CDK4 and
      CDK6 expression. Our findings suggest that fucoidan inhibits proliferation
      through AMPK-associated suppression of fatty acid synthesis and G1/S transition
      in HLF cells.

PMID- 25776105
TI  - Exploratory Evaluation and Initial Adaptation of a Parent Training Program for
      Hispanic Families of Children with Autism.
AB  - The present paper takes a translational approach in applying the themes of the
      current special section to prevention and intervention science in Latino
      families. The paper reviews the current literature on cultural processes in
      prevention and intervention research with Latino families. Overall, many
      prevention and intervention programs have either been developed specifically for
      Latino families or have been modified for Latino families with great attention
      paid to the socio-cultural needs of these families. Nevertheless, few studies
      have tested the role of cultural values or acculturation processes on outcomes.
      We make recommendations based on findings within basic science and in particular
      this special section on the incorporation of these values and processes into
      prevention and intervention science with Latino families. 

PMID- 25776106
TI  - Laser skin resurfacing: a patient-centred classification based on downtime.

PMID- 25776107
TI  - MTPs are a peripheral source of nociception.

PMID- 25776109
TI  - Metabolic gene expression shift by Listeria monocytogenes in coculture biofilms.
AB  - Coculture communities of microbes are more realistic and common in nature than in
      laboratory-grown pure cultures. In a mixed community, when resources with a
      potential role in growth are shared, conflict (as a consequence of competition)
      or cooperation is certain. In our study, this situation of conflict and
      cooperation was explored to understand the population dynamics and community
      behavior of Listeria monocytogenes. The social behavioral response of L.
      monocytogenes to the presence of Bacillus subtilis was studied in terms of
      divergence in gene expression of L. monocytogenes. It is evident from the results
      that social behavior of L. monocytogenes changes from competition for survival in
      broth to cooperation and coexistence in biofilm. Furthermore, the gene expression
      pattern is clearly indicative of L. monocytogenes switching from aerobic to
      fermentative metabolism in broth and biofilm conditions, respectively. 

PMID- 25776110
TI  - The effects of moms and teens for safe dates: a dating abuse prevention program
      for adolescents exposed to domestic violence.
AB  - Adolescents exposed to domestic violence are at high risk for dating abuse. This
      randomized controlled trial evaluated a dating abuse prevention program designed
      specifically for this risk group. Moms and Teens for Safe Dates consisted of six
      mailed booklets of dating abuse prevention information and interactive
      activities. Mothers who had been victims of domestic violence but no longer lived
      with the abuser delivered the program to their adolescents who had been exposed
      to the abuse. Mother and adolescent pairs (N = 409) were recruited through
      community advertising; the adolescents ranged from 12 to 16 years old and 64 %
      were female. Mothers and adolescents completed baseline and 6-month follow-up
      telephone interviews. Booklet completion in the treatment group ranged from 80 %
      for the first to 62 % for the last booklet. The analyses first tested whether
      program effects on dating abuse varied by four a priori identified moderators
      (mother's psychological health, the amount of adolescent exposure to domestic
      violence, and adolescent sex and race/ethnicity). Main effects of the program
      were examined when there were no differential program effects. Program effects on
      psychological and physical victimization and psychological and cyber perpetration
      were moderated by the amount of adolescent exposure to domestic violence; there
      were significant favorable program effects for adolescents with higher, but not
      lower levels of exposure to domestic violence. There were no moderated or main
      effects on sexual violence victimization and perpetration or cyber victimization.
      The findings suggest that a dating abuse prevention program designed for
      adolescents exposed to domestic violence can have important positive effects. 

PMID- 25776111
TI  - Anomalous left pulmonary artery origin from internal carotid artery: prospective
      echocardiographic diagnosis of a previously unknown variant.
AB  - We present a neonate with dextrocardia, tetralogy of Fallot, right arch, and
      aberrant left subclavian artery with left pulmonary artery origin from the left
      internal carotid artery, which is previously unreported. 

PMID- 25776113
TI  - Embracing change.

PMID- 25776112
TI  - Disease activity in rheumatoid arthritis and the risk of cardiovascular events.
AB  - OBJECTIVE: Use of several immunomodulatory agents has been associated with
      reduced numbers of cardiovascular (CV) events in epidemiologic studies of
      rheumatoid arthritis (RA). However, it is unknown whether time-averaged disease
      activity in RA correlates with CV events. METHODS: We studied patients with RA
      whose cases were followed in a longitudinal US-based registry. Time-averaged
      disease activity was assessed during followup using the area under the curve of
      the Clinical Disease Activity Index (CDAI), a validated measure of RA disease
      activity. Age, sex, presence of diabetes mellitus, hypertension, or
      hyperlipidemia, body mass index, family history of myocardial infarction (MI),
      use of aspirin or nonsteroidal antiinflammatory drugs (NSAIDs), presence of CV
      disease, and baseline use of an immunomodulator were assessed at baseline. Cox
      proportional hazards regression models were examined to determine the risk of a
      composite CV end point that included MI, stroke, and death from CV causes.
      RESULTS: A total of 24,989 patients who had been followed up for a median of 2.7
      years were included in these analyses. During followup, we observed 534 confirmed
      CV end points, for an incidence rate of 7.8 per 1,000 person-years (95%
      confidence interval [95% CI] 6.7-8.9). In models adjusted for variables noted
      above, a 10-point reduction in the time-averaged CDAI was associated with a 21%
      reduction in CV risk (95% CI 13-29). These results were robust in subgroup
      analyses stratified by the presence of CV disease, use of corticosteroids, use of
      NSAIDs or selective cyclooxygenase 2 inhibitors, and change in RA treatment, as
      well as when restricted to events adjudicated as definite or probable.
      CONCLUSION: Our findings showed that reduced time-averaged disease activity in RA
      is associated with fewer CV events.

PMID- 25776114
TI  - Ultrasound vs MRI for stroke shoulder: Apples and pears or simply N/A?

PMID- 25776115
TI  - Letter to the editor.

PMID- 25776116
TI  - Noninvasive neurostimulation in chronic stroke: a double-blind randomized sham
      controlled testing of clinical and corticomotor effects.
AB  - BACKGROUND: Repetitive peripheral magnetic stimulation (RPMS) is a painless and
      noninvasive method to produce afferents via the depolarization of the peripheral
      nervous system. A few studies tested RPMS after-effects on cerebral plasticity
      and motor recovery in stroke individuals, but evidences remain limited.
      OBJECTIVES: This study aimed to explore whether RPMS could mediate improvements
      in corticomotor and clinical outcomes associated with ankle impairments in
      chronic stroke. METHODS: Eighteen subjects with chronic stroke were randomly
      allocated to RPMS or sham group and compared to 14 healthy subjects. Stimulation
      was applied over the paretic tibialis anterior (TA). Ankle impairments on the
      paretic side and ipsilesional TA cortical motor representation were tested
      clinically and by transcranial magnetic stimulation (TMS), respectively. RESULTS:
      In the RPMS group, ankle dorsiflexion mobility and maximal isometric strength
      increased and resistance to plantar flexor stretch decreased. The magnitude of
      change seemed to be related to cortical and corticospinal integrity. Sham
      stimulation yielded no effect. Changes in TMS outcome and their relationships
      with clinical improvements were limited. CONCLUSIONS: RPMS improved ankle
      impairments in chronic stroke likely by a dynamic influence of sensory inputs on
      synaptic plasticity. The neurophysiological mechanisms potentially underlying the
      clinical effects are unclear. More studies are warranted to test the spinal and
      hemispheric changes responsible for the clinical improvements with emphasis on
      circuits spared by the lesion.

PMID- 25776117
TI  - A one-year follow-up after modified constraint-induced movement therapy for
      chronic stroke patients with paretic arm: a prospective case series study.
AB  - BACKGROUND: Despite the confirmed short-term effects of constraint-induced
      movement therapy, the long-term effects have not been sufficiently verified in
      terms of functional improvement of the affected arm. OBJECTIVE: To evaluate the
      long-term effects and relationship between arm use in activities of daily living
      and arm improvement with modified constraint-induced movement therapy in chronic
      stroke patients. METHODS: At 1 year after completing modified constraint-induced
      movement therapy, arm function (Fugl-Meyer Assessment) and amount of daily arm
      use (motor activity log) were assessed. RESULTS: Fourteen post-stroke patients
      with mild to moderate impairment of arm function were analyzed. One year after
      completing modified constraint-induced movement therapy, participants
      consistently showed improvements in arm function and amount of daily arm use
      (analysis of variance: Fugl-Meyer Assessment, P < 0.001; Motor Activity Log, P <
      0.001). For the Fugl-Meyer Assessment, post-hoc tests detected significant
      improvements (pre versus post, P = 0.009; pre versus 1 year, P < 0.0001; post
      versus 1 year, P < 0.036). For the Motor Activity Log, post-hoc tests also
      detected significant improvements (pre versus post, P = 0.0001; pre versus 1
      year, P < 0.0001; post versus 1 year, P = 0.0014). The magnitude of the change in
      Fugl-Meyer Assessment score correlated significantly with the change in Motor
      Activity Log score (R = 0.778, P = 0.001). CONCLUSIONS: Among post-stroke
      patients with mild to moderate impairments of arm function, modified constraint
      induced movement therapy without any other rehabilitation after intervention may
      improve arm function and increase arm use for 1 year. In addition, increasing arm
      use may represent an important factor in improving arm function, and vice versa.

PMID- 25776118
TI  - Real-world affected upper limb activity in chronic stroke: an examination of
      potential modifying factors.
AB  - BACKGROUND: Despite improvement in motor function after intervention, adults with
      chronic stroke experience disability in everyday activity. Factors other than
      motor function may influence affected upper limb (UL) activity. OBJECTIVE: To
      characterize affected UL activity and examine potential modifying factors of
      affected UL activity in community-dwelling adults with chronic stroke. METHODS:
      Forty-six adults with chronic stroke wore accelerometers on both ULs for 25 hours
      and provided information about potential modifying factors [time spent in
      sedentary activity, cognitive impairment, depressive symptomatology, number of
      comorbidities, motor dysfunction of the affected UL, age, activities of daily
      living (ADL) status, and living arrangement]. Accelerometry was used to quantify
      duration of affected and unaffected UL activity. The ratio of affected-to
      unaffected UL activity was also calculated. Associations within and between
      accelerometry-derived variables and potential modifying factors were examined.
      RESULTS: Mean hours of affected and unaffected UL activity were 5.0 +/- 2.2 and
      7.6 +/- 2.1 hours respectively. The ratio of affected-to-unaffected UL activity
      was 0.64 +/- 0.19, and hours of affected and unaffected UL activity were strongly
      correlated (r = 0.78). Increased severity of motor dysfunction and dependence in
      ADLs were associated with decreased affected UL activity. No other factors were
      associated with affected UL activity. CONCLUSIONS: Severity of motor dysfunction
      and ADL status should be taken into consideration when setting goals for UL
      activity in people with chronic stroke. Given the strong, positive correlation
      between affected and unaffected UL activity, encouragement to increase activity
      of the unaffected UL may increase affected UL activity.

PMID- 25776119
TI  - Effect of task-oriented training for people with stroke: a meta-analysis focused
      on repetitive or circuit training.
AB  - PURPOSE: The current meta-analysis reviewed evidence for effective task-oriented
      training focused on repetitive or circuit training after stroke. METHOD: Searches
      were conducted of randomized, controlled trials using task-oriented training. The
      quality of each study was assessed using the Physiotherapy Evidence Database
      (PEDro) scale. Eleven studies were analyzed regarding the magnitude of effect
      sizes (ESs) and categorized according to extremities focused upon for training,
      outcome measures, and study variables. This included duration and frequency of
      training and stroke stage. RESULTS: The PEDro scores ranged from 4 to 8 (median =
      7). The overall ES of the 11 studies was large. The effects for lower extremities
      and both acute/sub-acute and chronic stage stroke were large and significant.
      Significant effects were also found for gait velocity, gait endurance, balance,
      timed up and go test, and strength of the lower extremities. There was no
      significant effect of training focused on upper extremities. Training with a
      duration of 2 weeks and frequency of 7 days a week had the greatest effects.
      CONCLUSIONS: Task-oriented training interventions are useful for improving muscle
      strength and gait related activities in both acute/sub-acute and chronic stroke
      patients. Although this meta-analysis provides evidence of task-oriented training
      for improving functioning after stroke, further studies are necessary to
      investigate the effects of training on upper extremities and the overall cost
      effectiveness of such training.

PMID- 25776120
TI  - Motor and sensory effects of ipsilesional upper extremity hypothermia and
      contralesional sensory training for chronic stroke patients.
AB  - As hypothermia by immersion can reduce the sensory nerve conduction velocity,
      this study hypothesized that the reduction of sensory input to the ipsilesional
      upper extremity (UE) using cryotherapy would reduce the inhibitory activity of
      the contralesional hemisphere in chronic stroke subjects. OBJECTIVE: In this
      study, hypothermia was applied by immersing the ipsilesional UE in association
      with sensory training of the contralesional UE of stroke patients to assess the
      immediate (e.g. sensorimotor function, hemodynamics, and levels of comfort) and
      long-term (sensory and motor performances of the UEs) effects. METHODS: The
      sample included 27 stroke patients allocated into group 1 (n = 14), which
      received conventional physiotherapy for the affected UE, and group 2 (n = 13),
      which underwent 10 sessions of immersion hypothermia of the ipsilesional wrist
      and hand. Assessments were performed pre- and post-treatment and at follow-up
      using esthesiometry, the Fugl-Meyer Assessment (FMA), the Nottingham Sensory
      Assessment, functional tests, tactile and weight discrimination, motor sequence,
      level of comfort, and hemodynamic parameters. RESULTS: The immediate effects of
      hypothermia using immersion of the ipsilesional UE in association with sensory
      training of the contralesional UE were hemodynamic stability during and after
      hypothermia, the absence of sensory abnormalities in the contralesional UE,
      hypoesthesia in the ipsilesional extremity (dermatomes C6 and C8) (P < 0.05), the
      maintenance of acceptable levels of comfort, and good patient compliance to the
      technique. The long-term effects included significant increases in scores on
      tests performed without functional vision, in scores on blindfolded functional
      tests, and in tactile localization and joint position sense for the
      contralesional hand in group 2 as well as the maintenance of these gains at long
      term follow-up (5 weeks). Improvement was also found in the tactile function of
      the C6 and C7 dermatomes of the contralesional hand (P < 0.05). CONCLUSIONS: The
      use of immersion hypothermia on the ipsilesional UE in association with sensory
      training of the contralesional UE improved motor function and sensitivity in the
      contralesional UE of individuals with chronic stroke. Immersion hypothermia of
      the ipsilesional UE in chronic stroke patients is a safe, practical, inexpensive,
      and easily applied technique.

PMID- 25776121
TI  - Efficiency of unimanual and bimanual reach in persons with and without stroke.
AB  - BACKGROUND: Deficiencies in motor control are one of the largest challenges faced
      by stroke survivors in regaining their independence after stroke. OBJECTIVE: This
      study investigated movement efficiency in people with and without stroke during
      both unimanual and bimanual upper extremity reaching tasks. METHOD: Twenty-five
      participants (12 with stroke and 13 age-matched controls) between the ages of 36
      69 years randomly experienced testing conditions involving reaching forward
      unimanually and bimanually at a preferred speed in a single session. Kinematic
      and kinetic outcomes included movement time, movement units, peak velocity, and
      percentage of movement time to peak velocity. RESULTS: In stroke participants,
      the unimpaired limb accommodated its movements to that of the less efficient
      paretic limb during bimanual conditions indicating yoked movement efficiency
      because its performance was more efficient (P < 0.05) in unilateral trials,
      whereas the impaired limb's performance did not differ between the unimanual and
      bimanual conditions (P>0.05). Control subjects elicited greater movement
      efficiency than participants with stroke. CONCLUSION: Motor efficiency of the
      unimpaired upper extremity may be adversely influenced when yoked with the
      impaired limb during symmetrical simple movements in persons with stroke. As
      such, motor efficiency is not exclusively limited to the impaired side, the
      effects of which may be task dependent.

PMID- 25776122
TI  - Factors related to community ambulation in patients with chronic stroke.
AB  - BACKGROUND: The focus of gait rehabilitation for walking in real-life settings
      should vary according to different aspects of gait performance. Investigation of
      factors related to impairments specific to community ambulation or activity
      participation may be helpful in determining and targeting appropriate treatment
      for gait rehabilitation. Objective To investigate the relationship between
      community ambulation and factors determining gait ability. Methods Forty-six
      outpatients with a previous stroke participated in a cross-sectional assessment.
      Community ambulation was assessed using a self-administered questionnaire.
      Outcome measures included impairments (strength, sensation, muscle tone, and
      balance) and ambulatory activity limitations (self-paced and maximum 10-m gait
      speed, 6-minute walking test, and concurrent manual/cognitive dual-task walking
      speed). Ability to increase speed and the dual-tasks cost were calculated.
      Multivariate analysis of variance and multiple regression analyses were used to
      determine differences in walking and identify important factors related to
      community ambulation. Results Pearson and Spearman analyses revealed that
      impairments (balance, r = .665; muscle strength, r = 0.653) and ambulatory
      activity limitation (gait speed, r = 0.684; walking distance, r = 0.654; ability
      to increase speed, r = 0.413) were significantly positively correlated with
      community ambulation level. Balance was an important factor in predicting
      increasing speed (P < 0.001). Muscle strength and tone were positive contributors
      to gait speed (P = 0.001 for both) and distance (P = 0.019 and P = 0.002,
      respectively). Cognitive and manual dual tasks showed no significant relationship
      to other variables. Stepwise multivariate regression analysis showed that
      important determinants of community ambulation level were strength (P < 0.001)
      and gait endurance (P = 0.001). Conclusions Muscle strength and walking distance
      are contributing factors in community ambulation for patients with chronic
      stroke.

PMID- 25776123
TI  - Efficacy of adhesive taping as an adjunt to physical rehabilitation to influence
      outcomes post-stroke: a systematic review.
AB  - BACKGROUND: Adhesive taping as a therapeutic modality post-stroke has been
      investigated for two decades. No systematic review of the evidence to inform
      clinical practice exists. OBJECTIVE: To systematically review the efficacy of
      adhesive taping as an adjunct to physical rehabilitation on outcomes related to
      body function and structure, activity, and participation post-stroke. METHODS:
      The databases of PubMed, CINAHL, EMBASE, and Web of Science from 1966 through
      December 2013 were searched. Full-text articles in English from peer-reviewed
      journals reporting original research on the use of adhesive taping post-stroke
      were included. Two reviewers independently searched and then rated the quality of
      evidence using the PEDro evidence rating system. Randomized controlled trials
      were further assessed using the Consolidated Standards of Reporting Trials
      (CONSORT) guidelines. RESULTS: Fifteen studies met the inclusion criteria. Two
      used elastic tape and 13 used rigid tape. The evidence quality ranged from poor
      to good, and included seven shoulder, one wrist, two hip, one knee, and four
      ankle studies. There were four good-quality studies. CONCLUSIONS: Preliminary
      evidence in the domain of body function and structure suggests that use of rigid
      adhesive tape as an adjunct may increase the number of pain-free days at the
      shoulder. Evidence for the improvement of pain intensity, range of motion, muscle
      tone, strength, or function with taping is inconclusive. The evidence related to
      activity and participation is insufficient. The use of adhesive taping post
      stroke needs further and more rigorous research to compare the types, methods and
      dosage of taping.

PMID- 25776124
TI  - Inferring the demographic history of Drosophila subobscura from nucleotide
      variation at regions not affected by chromosomal inversions.
AB  - Drosophila subobscura presents a rich and complex chromosomal inversion
      polymorphism. It can thus be considered a model system (i) to study the
      mechanisms originating inversions and how inversions affect the levels and
      patterns of variation in the inverted regions and (ii) to study adaptation at
      both the single-gene and chromosomal inversion levels. It is therefore important
      to infer its demographic history as previous information indicated that its
      nucleotide variation is not at mutation-drift equilibrium. For that purpose, we
      sequenced 16 noncoding regions distributed across those parts of the J chromosome
      not affected by inversions in the studied population and possibly either by other
      selective events. The pattern of variation detected in these 16 regions is
      similar to that previously reported within different chromosomal arrangements,
      suggesting that the latter results would, thus, mainly reflect recent demographic
      events rather than the partial selective sweep imposed by the origin and
      frequency increase of inversions. Among the simple demographic models considered
      in our Approximate Bayesian Computation analysis of variation at the 16 regions,
      the model best supported by the data implies a population size expansion soon
      after the penultimate glacial period. This model constitutes a better null model,
      and it is therefore an important resource for subsequent studies aiming among
      others to uncover selective events across the species genome. Our results also
      highlight the importance of introducing the possibility of multiple hits in the
      coalescent simulations with an outgroup. 

PMID- 25776129
TI  - Changes in serum and urine SAA concentrations and qualitative and quantitative
      proteinuria in Abyssinian cats with familial amyloidosis: a five-year
      longitudinal study (2009-2014).
AB  - BACKGROUND: Diagnosis of familial amyloidosis (FA) in Abyssinian cats usually is
      made on postmortem examination. HYPOTHESIS/OBJECTIVES: Sequential analysis of
      serum SAA (sSAA), urinary SAA (uSAA), urinary protein:creatinine (UPC) ratio, or
      sodium-dodecylsulfate agarose gel electrophoresis (SDS-AGE) may facilitate early
      identification of cats with FA. ANIMALS: Twenty-three Abyssinian cats belonging
      to cattery A or B (low and high prevalence of FA, respectively). METHODS:
      Prospective longitudinal study using 109 blood and 100 urine samples collected
      over 4-year period every 4 months, if possible, or more frequently in case of
      illness. Cats that died during study were necropsied. Health status of live cats
      was checked 5 years after enrollment. Serum amyloid A (sSAA) and urinary SAA
      (uSAA) were measured using ELISA kit. The UPC ratio and SDS-AGE also was
      performed. RESULTS: Familial amyloidosis was not identified in cattery A, whereas
      7/14 cats from cattery B had FA. Serum amyloid A concentrations were not
      significantly different between cats in catteries A and B or between cats with or
      without FA, despite frequent peaks in cats from cattery B. Conversely, uSAA was
      significantly higher in cattery B, especially in the terminal phases of FA.
      Proteinuria occasionally was found in cats from both catteries, especially in
      those with FA. Urine protein electrophoresis identified mixed proteinuria only in
      cats with FA. CONCLUSIONS AND CLINICAL IMPORTANCE: Serum amyloid A and UPC ratio
      are not helpful for early identification of Abyssinian cats with FA. Conversely,
      increases in uSAA with or without mixed proteinuria may be found before onset of
      clinical signs in cats with FA.

PMID- 25776130
TI  - Safety and efficacy results of switch from imiglucerase to velaglucerase alfa
      treatment in patients with type 1 Gaucher disease.
AB  - Gaucher disease (GD) is a lysosomal storage disorder; symptomatic patients with
      type 1 GD need long-term disease-specific therapy of which the standard of care
      has been enzyme replacement therapy (ERT). Thirty-eight of 40 patients (aged 9-71
      years) clinically stable on ERT with imiglucerase, safely switched to a
      comparable dose of velaglucerase alfa (units/kg) during TKT034, a 12-month, open
      label clinical study, and for 10-50 months in an extension study. The most common
      adverse events (AEs) judged to be drug-related in the extension were fatigue and
      bone pain. No drug-related serious AEs were reported. No AEs led to study
      withdrawal. At 24 months from baseline (baseline being TKT034 week 0), patients
      had generally stable hemoglobin, platelet, spleen, liver, and bone density
      parameters. Nevertheless, dose adjustment based on the achievement of therapeutic
      goals was permitted, and 10 patients, including seven patients who had platelet
      counts <100 * 10(9) /L at baseline, were given at least one 15 U/kg-dose increase
      during the extension. Trends indicative of improvement in platelet count and
      spleen volume, and decreasing levels of GD biomarkers, chitotriosidase and CCL18,
      were observed. Immunogenicity was seen in one patient positive for anti
      imiglucerase antibodies at baseline. This patient tested positive for anti
      velaglucerase alfa antibodies in TKT034, with low antibody concentrations, and
      throughout the extension study; however, the patient continued to receive
      velaglucerase alfa without clinical deterioration. In conclusion, clinically
      stable patients can be switched from imiglucerase to velaglucerase alfa ERT and
      maintain or achieve good therapeutic outcomes.

PMID- 25776131
TI  - Large room-temperature electroresistance in dual-modulated ferroelectric tunnel
      barriers.
AB  - Pt/BaTiO3/La0.7Sr0.3MnO3 tunnel junctions, at negative voltage bias, for two
      polarization directions are represented. It is demonstrated that reversing the
      polarization direction of a ferroelectric barrier in a tunnel junction leads to a
      change of junction conductance and capacitance, with concomitant variations on
      the barrier height and effective thickness, both contributing to produce larger
      electroresistance.

PMID- 25776132
TI  - A successful case of liver biopsy via the right femoral vein using the Quick-Core
      biopsy needle.
AB  - A 35-year-old male with ascites and coagulopathy underwent transjugular liver
      biopsy (TJLB) for severe hepatic dysfunction. However, the acute angle of the
      inferior vena cava and hepatic veins (HVs) prevented insertion of a 14-gauge
      inner stiffening metallic cannula into the HV. He then underwent successful liver
      biopsy by right femoral vein access (transfemoral liver biopsy) using a TJLB
      device without complications and was pathologically diagnosed with nonalcoholic
      steatohepatitis. 

PMID- 25776133
TI  - Identifying attentional deployment tactics in older adults' written narratives
      about emotionally upsetting events.
AB  - Essays about distressing events written by 58 older adults on three occasions (n
      = 174) were coded to identify how older adults responded when confronting an
      emotionally upsetting event. Participants limited the experience of negative
      emotion by transitioning from negative to positive aspects of the event within a
      writing session, and across sessions, switched writing topics and moved from
      writing about past events to current problems. The use of attentional deployment
      tactics was associated with lower negative affect. This study confirms results
      found in quantitative studies and uncovers new processes that promote emotion
      regulation.

PMID- 25776134
TI  - Risk factors and antibiotic therapy in P. aeruginosa community-acquired
      pneumonia.
AB  - BACKGROUND AND OBJECTIVE: Current guidelines recommend empirical treatment
      against Pseudomonas aeruginosa in community-acquired pneumonia (CAP) patients
      with specific risk factors. However, evidence to support these recommendations is
      limited. We evaluate the risk factors and the impact of antimicrobial therapy in
      patients hospitalized with CAP due to P. aeruginosa. METHODS: We performed a
      retrospective population-based study of >150 hospitals. Patients were included if
      they had a diagnosis of CAP and P. aeruginosa was identified as the causative
      pathogen. Univariate and multivariate analyses were performed using the presence
      of risk factors and 30-day mortality as the dependent measures. RESULTS: Seven
      hundred eighty-one patients with P. aeruginosa pneumonia were identified in a
      cohort of 62 689 patients with pneumonia (1.1%). Of these, 402 patients (0.6%)
      were included in the study and 379 (0.5%) were excluded due to health care
      associated pneumonia or immunosuppression. In patients with CAP due to P.
      aeruginosa, 272 (67.8%) had no documented risk factors. These patients had higher
      rates of dementia and cerebrovascular disease. Empirical antibiotic therapy
      against P. aeruginosa within the first 48 h of presentation was independently
      associated with lower 30-day mortality in patients with CAP due to P. aeruginosa
      (hazard ratio (HR) 0.42, 95% confidence interval (CI): 0.23-0.76) and in patients
      without risk factors for P. aeruginosa CAP (HR 0.40, 95% CI: 0.21-0.76).
      CONCLUSIONS: Risk factor recommended by current guidelines only detect one third
      of the patients admitted with CAP due to P. aeruginosa. Risk factors did not
      define the whole benefit observed due to empirical therapy covering P.
      aeruginosa.

PMID- 25776135
TI  - Ginsenoside Re Promotes Nerve Regeneration by Facilitating the Proliferation,
      Differentiation and Migration of Schwann Cells via the ERK- and JNK-Dependent
      Pathway in Rat Model of Sciatic Nerve Crush Injury.
AB  - Exploring effective drugs that are capable of promoting nerve regeneration has
      gained much attention. Ginsenoside Re (Re) is the main ingredient of ginseng
      berries and roots. Research in the area has shown that ginsenoside Re exhibits
      multiple pharmacological activities via different mechanisms both in vivo and in
      vitro. But the potential therapeutic effects of Re on sciatic nerve crush injury
      (SNC) have been little investigated. Herein, we investigated the protect effect
      of Re on peripheral nerve regeneration in a rat SNC model. Walking track analysis
      revealed that Re treatment significantly promoted functional recovery of crushed
      sciatic nerve in rats. The expression of PCNA in rat sciatic nerve was up
      regulated by Re treatment, and peaked when the concentration of Re was 2.0 mg/kg.
      Using immunofluorescent staining, we found that Re greatly increased the
      expression of GAP-43 and S100 in injured rat sciatic nerve. Furthermore, we
      evaluated the effects of Re on proliferation, differentiation, and migration of
      Schwann cells in SNC rat models. Our studies reveal that Re promotes nerve
      regeneration is depend on ERK1/2 and JNK1/2 signaling pathway. Elevated Oct-6
      expression and featured morphological changes indicated that Re facilitated the
      differentiation of Schwann cells following SNC. Also, transwell and wound-healing
      assay demonstrated that the migration capabilities of Schwann cell were
      significantly enhanced after Re treatment. 

PMID- 25776136
TI  - PEG-PEI/siROCK2 Protects Against Abeta42-Induced Neurotoxicity in Primary Neuron
      Cells for Alzheimer Disease.
AB  - Gene therapy that targets the ROCK2 gene has yielded promising results in the
      treatment of AD. Our previous study indicated that PEG-PEI/siROCK2 could
      effectively suppress ROCK2 mRNA expression and showed a promising prospect for
      the treatment of Alzheimer's disease. However, the ability of PEG-PEI/siROCK2 to
      reduce Abeta-induced cytotoxicity is unknown. To investigate the effect of PEG
      PEI/siROCK2 against Abeta42-induced neurotoxicity, primary cultured cortical
      neurons were pretreated with PEG-PEI/siROCK2 for 24 h and then treated with 5 MUM
      Abeta42 for 24 h. We found that PEG-PEI/siROCK2 increased the cell viability and
      reduced the number of apoptotic cells induced by Abeta42, as measured using an
      MTT assay and Annexin V/PI staining. A further study revealed that PEG
      PEI/siROCK2 can activate p-Akt, and treatment with the PI3K inhibitor LY294002
      attenuated the neuroprotective effects. These results suggest that PEG
      PEI/siROCK2 prevents Abeta42-induced neurotoxicity and that the activation of
      PI3K/Akt pathway is involved in neuroprotection. Taken together, these findings
      shed light on the role of PEG-PEI/siROCK2 as a potential therapeutic agent for
      AD. 

PMID- 25776138
TI  - Insulin pump risks and benefits: a clinical appraisal of pump safety standards,
      adverse event reporting, and research needs: a joint statement of the European
      Association for the Study of Diabetes and the American Diabetes Association
      Diabetes Technology Working Group.
AB  - Insulin pump therapy, also known as continuous subcutaneous insulin infusion
      (CSII), is an important and evolving form of insulin delivery, which is mainly
      used for people with type 1 diabetes. However, even with modern insulin pumps,
      errors of insulin infusion can occur due to pump failure, insulin infusion set
      (IIS) blockage, infusion site problems, insulin stability issues, user error, or
      a combination of these. Users are therefore exposed to significant and
      potentially fatal hazards: interruption of insulin infusion can result in
      hyperglycemia and ketoacidosis; conversely, delivery of excessive insulin can
      cause severe hypoglycemia. Nevertheless, the available evidence on the safety and
      efficacy of CSII remains limited. The European Association for the Study of
      Diabetes (EASD) and the American Diabetes Association (ADA) have therefore joined
      forces to review the systems in place for evaluating the safety of pumps from a
      clinical perspective. We found that useful information held by the manufacturing
      companies is not currently shared in a sufficiently transparent manner. Public
      availability of adverse event (AE) reports on the US Food and Drug
      Administration's Manufacturer and User Facility Device Experience (MAUDE)
      database is potentially a rich source of safety information but is insufficiently
      utilized due to the current configuration of the system; the comparable database
      in Europe (European Databank on Medical Devices [EUDAMED]) is not publicly
      accessible. Many AEs appear to be attributable to human factors and/or user
      error, but the extent to which manufacturing companies are required by regulators
      to consider the interactions of users with the technical features of their
      products is limited. The clinical studies required by regulators prior to
      marketing are small and over-reliant on bench testing in relation to "predicate"
      products. Once a pump is available on the market, insufficient data are made
      publicly available on its long-term use in a real-world setting; such data could
      provide vital information to help health care teams to educate and support users
      and thereby prevent AEs. As well as requiring more from the manufacturing
      companies, we call for public funding of more research addressing clinically
      important questions in relation to pump therapy: both observational studies and
      clinical trials. At present, there are significant differences in the regulatory
      systems between the US and European Union at both pre- and postmarketing stages;
      improvements in the European system are more urgently required. This statement
      concludes with a series of recommended specific actions for "meknovigilance"
      (i.e., a standardized safety approach to technology) that could be implemented to
      address the shortcomings we highlight. 

PMID- 25776137
TI  - 4-Phenylbutyric Acid (4-PBA) and Lithium Cooperatively Attenuate Cell Death
      during Oxygen-Glucose Deprivation (OGD) and Reoxygenation.
AB  - Hypoxia is an important cause of brain injury in ischemic stroke. It is known
      that endoplasmic reticulum (ER) stress is an important determinant of cell
      survival or death during hypoxia. However, the signaling pathways and molecular
      mechanisms involved remain to be studied in more detail. To investigate whether
      inhibition of ER stress promotes neuroprotection pathways, we applied an in vitro
      oxygen-glucose deprivation (OGD) followed by reoxygenation model of human SK-N-MC
      neuronal cell cultures in this study. Our results showed that neuronal cell death
      was induced in this model during the OGD reoxygenation by the sustained ER
      stress, but not during OGD phase. However, treatment of the cultures with lithium
      with the OGD reoxygenation insult did not result in neuroprotection, whereas
      concomitant treatment of chemical chaperon 4-phenylbutyric acid (4-PBA) provides
      protective effects in ER stress-exposed cells. Moreover, 4-PBA rescued ER stress
      suppressed Akt protein biosynthesis, which works cooperatively with lithium in
      the activation of Akt downstream signaling by inhibition of autophagy-induced
      cell death. Taken together, our finding provides a possible mechanism by which 4
      PBA and lithium contribute to mediate neuroprotection cooperatively. This result
      may potentially be a useful therapeutic strategy for ischemic stroke. 

PMID- 25776139
TI  - Knee Extensor Muscle Strength in Middle-Aged and Older Individuals Undergoing
      Arthroscopic Partial Meniscectomy: A Systematic Review and Meta-Analysis.
AB  - OBJECTIVE: People with meniscal tears are at high risk to develop or progress to
      knee osteoarthritis. Knee extensor weakness is considered a risk factor for
      osteoarthritis and is often reported in these individuals. The purpose of this
      systematic review and meta-analysis was to investigate knee extensor strength in
      people undergoing an arthroscopic partial meniscectomy (APM). METHODS: Six
      databases (Medline, CINAHL, SPORTDiscus, Embase, PEDro, and AMED) were searched
      up to June 22, 2014. Studies that measured knee extensor muscle strength in
      people age >=30 years undergoing APM for a meniscal tear and used either a
      healthy control group or the contralateral leg to compare knee extensor muscle
      strength were included. Methodological quality was assessed using guidelines from
      the Centre for Reviews and Dissemination. RESULTS: Eleven studies, in which
      participants were predominantly male, were included (n = 596). A moderate
      reduction in muscle strength was observed prior to APM compared to controls
      (standardized mean difference [SMD] 0.58, 95% confidence interval [95% CI] 0.04,
      1.13) and continued up to 6 months postsurgery (SMD range -2.42 to -0.47). There
      was no difference in muscle strength at 2 years post-APM (SMD -0.01 [95% CI 
      0.36, 0.35]), while a moderate reduction was again apparent at 4 years post-APM
      (SMD -0.56, [95% CI -1.20, 0.08]) compared to controls. CONCLUSION: Our findings
      suggest that middle-aged and older individuals undergoing APM have reduced knee
      extensor muscle strength in the operated leg compared to control data. As
      meniscus pathology and knee extensor muscle weakness are risk factors for
      osteoarthritis, these results highlight the clinical importance of addressing
      muscle weakness in these individuals.

PMID- 25776140
TI  - Cutaneous vasculitidis: histology and immunofluorescence.
AB  - Cutaneous vasculitis comprises a wide spectrum of diseases that involve
      predominantly the blood vessels and surrounding tissues of the skin. Few
      vasculitic syndromes have pathognomonic clinical, radiographic and/or laboratory
      findings; thus, confident and accurate diagnosis of vasculitis requires
      histological confirmation. Skin biopsy should be done, optimally within 24 to 48
      hours after vasculitic lesions appear. Deep excision biopsy must be preferred.
      Direct immunofluorescence of lesional skin is helpful in the diagnosis of
      vasculitides in the light of a proper clinico-pathological setting and diagnostic
      in some peculiarly forms. Cutaneous histological patterns can be used to generate
      relevant clinical differential diagnoses, and, when coupled with patient's
      history, clinical and laboratory data, allow more precise and accurate diagnosis
      of vasculitic syndromes. This review will focus on histopathological and
      immunologic pattern of the more common cutaneous vasculitis syndromes, based on
      the 2012 Revised International CHCC. 

PMID- 25776141
TI  - Drug-induced cutaneous vasculitides.
AB  - Cutaneous vasculitides (CV) can be idiopathic or secondary to several triggers,
      including drugs, which account for up to 30% of all the cases of CV. Several
      drugs can induce CV, including some medications commonly used in dermatology,
      including minocycline, and several new drugs, such as anti-TNF agents. Different
      pathomecanisms are involved in the development of drug-induced CV, including the
      formation and deposition of immune complexes, the induction of neutrophil
      apoptosis, the formation of neoantigens between the drugs and proteins from the
      host, the shift of the immune response, and others. Although the diagnosis is
      difficult, because the clinical picture of drug-induced CV is in general
      indistinguishable from that of other forms of CV, it is important to recognize
      such entities in order to correctly manage the patient. Anamnesis, diagnostic
      algorithms to assess the likelihood of the association between a drug and a
      cutaneous reaction, skin biopsy and laboratory testing (including the search for
      antineutrophil cytoplasmic antibodies) are useful tools to make a diagnosis of
      drug-induced CV. About the therapy, while in idiopathic vasculitides the
      treatment is usually more aggressive and long-lasting, very often requiring a
      maintenance therapy with immunosuppressive drugs, in drug-induced CV the
      discontinuation of the suspected drug alone is usually enough to achieve complete
      remission, making the prognosis usually very good. 

PMID- 25776142
TI  - Classification and clinical diagnosis of cutaneous vasculitides.
AB  - The definition, diagnostic criteria and classification of systemic vasculitides,
      of which cutaneous vasculitides (CV) are a part, have long been discussed by the
      medical scientific world. The most significant contribution is due to the
      consensus-based criteria specifically derived by the combination of judgments
      from groups of experts, after accurate literature reviews and developed using
      consensus techniques. First of them came from the American College of
      Rheumatology (ACR) in 1990. In 1994 the Chapel Hill International Consensus
      Conference (CHCC) produced the Consensus-based Criteria essentially providing
      proper nomenclature for systemic vasculitis, which has been modified in 2012 by
      the CHCC2012. Moreover, in 2006 European League against Rheumatism and Pediatric
      Rheumatology European Society produced consensus criteria for the classification
      of childhood vasculitis. In CHCC2012 CV, affecting small vessels with a
      predominant skin involvement, have been included in both small vessel vasculitis
      and single organ vasculitis. The general characteristics of so-called CV have
      been described (epidemiology, clinical features, histopathology and
      etiopathogenesis) and, finally, the major characteristics of each clinical type
      of CV as well as their diagnostic criteria currently available in the literature
      have been reported. 

PMID- 25776143
TI  - Vasopressin V1a and V1b receptor modulators: a patent review (2012 - 2014).
AB  - INTRODUCTION: The vasopressin V1a and V1b receptors are involved in many crucial
      physiological, reproductive, behavioral and social functions. Consequently, they
      are also involved in several pathological conditions, thus the ligands capable of
      selective stimulation/inhibition of these receptors may present therapeutic
      benefit in a variety of diseases. AREAS COVERED: In this review, the author
      focuses on the vasopressin V1a and V1b receptors, their biological functions and
      agonists and antagonists patented in the years 2012 - 2014. This paper is divided
      according to both the target receptor and the applicant and describes the
      compounds from the patents along with their biological activity. EXPERT OPINION:
      In the recent years, pharmaceutical companies have discovered and patented new
      compounds which act through vasopressin V1a and/or V1b receptors, both peptide
      and non-peptide. Among the V1bR antagonists published in the last years, the
      oxindole derivatives appear to be the most promising drug candidates.

PMID- 25776145
TI  - Novel mutation in the BMPR1B gene (R486L) in a Polish family and further
      delineation of the phenotypic features of BMPR1B-related brachydactyly.
AB  - BACKGROUND: Lehmann et al., [2003, 2006] have documented two different
      substitutions at position 486 of the BMPR1B gene which resulted in a phenotype of
      brachydactyly A2 [MIM 112600] or brachydactyly C with symphalangism [MIM 113100].
      METHODS: In this article we report a family of Polish extraction with a novel
      mutation: c.1457G>T (R486L) which segregated with a complex brachydactyly.
      Clinical and radiological data are presented and details of previously reported
      patients with a pathogenic change of an amino acid at position 486 of the BMPR1B
      gene are summarized. CONCLUSION: Our data extends the previously known mutational
      and radiological spectrum associated with mutations in the BMPR1B gene and
      confirms the existence of a universal hotspot in the BMPR1B gene in this
      distinctive autosomal dominant brachydactyly disorder. It is of interest that an
      affected female in the Polish family had a severe congenital malformation of the
      venous system in addition to her digital anomalies. This observation raises the
      possibility of disturbance of embryonic angiogenesis by specific mutations in
      BMPR1B.

PMID- 25776183
TI  - Issues that impact type-2 diabetes self-management in rural communities.
AB  - PURPOSE: To evaluate and synthesize the evidence related to issues that impact
      type-2 diabetes self-management in rural communities. DATA SOURCES: A systematic
      review of the literature from 2008 to 2013 was conducted using the following
      health science databases: CINAHL, PubMed, Cochrane Library, and OVID. Other
      databases searched included the clearinghouses of the Centers for Disease Control
      (CDC); National Rural Health Association (NRHA), State Offices of Rural Health
      (SORH), and Rural Health Research & Policy Centers (RHRPC). Keywords used to
      obtain relevant articles included rural, type-2 diabetes self-management, health
      disparities, and nursing. CONCLUSION: Three themes emerged from the literature
      examined: barriers to type-2 diabetes self-management, provider tools and
      education enhance type-2 diabetes self-management, and recommendations and
      guidelines for diabetes self-management efficacy. IMPLICATIONS FOR PRACTICE: The
      information presented here will support healthcare providers in improving
      preventative care, providing optimal disease management, and assisting with
      successful type-2 diabetes self-management in rural populations.

PMID- 25776144
TI  - DNA methylation and hydroxymethylation in stem cells.
AB  - In mammals, DNA methylation and hydroxymethylation are specific epigenetic
      mechanisms that can contribute to the regulation of gene expression and cellular
      functions. DNA methylation is important for the function of embryonic stem cells
      and adult stem cells (such as haematopoietic stem cells, neural stem cells and
      germline stem cells), and changes in DNA methylation patterns are essential for
      successful nuclear reprogramming. In the past several years, the rediscovery of
      hydroxymethylation and the TET enzymes expanded our insights tremendously and
      uncovered more dynamic aspects of cytosine methylation regulation. Here, we
      review the current knowledge and highlight the most recent advances in DNA
      methylation and hydroxymethylation in embryonic stem cells, induced pluripotent
      stem cells and several well-studied adult stems cells. Our current understanding
      of stem cell epigenetics and new advances in the field will undoubtedly stimulate
      further clinical applications of regenerative medicine in the future.

PMID- 25776184
TI  - Emerging Updates on the Posterior Cruciate Ligament: A Review of the Current
      Literature.
AB  - The posterior cruciate ligament (PCL) is recognized as an essential stabilizer of
      the knee. However, the complexity of the ligament has generated controversy about
      its definitive role and the recommended treatment after injury. A proper
      understanding of the functional role of the PCL is necessary to minimize residual
      instability, osteoarthritic progression, and failure of additional concomitant
      ligament graft reconstructions or meniscal repairs after treatment. Recent
      anatomic and biomechanical studies have elucidated the surgically relevant
      quantitative anatomy and confirmed the codominant role of the anterolateral and
      posteromedial bundles of the PCL. Although nonoperative treatment has
      historically been the initial treatment of choice for isolated PCL injury,
      possibly biased by the historically poorer objective outcomes postoperatively
      compared with anterior cruciate ligament reconstructions, surgical intervention
      has been increasingly used for isolated and combined PCL injuries. Recent studies
      have more clearly elucidated the biomechanical and clinical effects after PCL
      tears and resultant treatments. This article presents a thorough review of
      updates on the clinically relevant anatomy, epidemiology, biomechanical function,
      diagnosis, and current treatments for the PCL, with an emphasis on the emerging
      clinical and biomechanical evidence regarding each of the treatment choices for
      PCL reconstruction surgery. It is recommended that future outcomes studies use
      PCL stress radiographs to determine objective outcomes and that evidence level 1
      and 2 studies be performed to assess outcomes between transtibial and tibial
      inlay reconstructions and also between single- and double-bundle PCL
      reconstructions. 

PMID- 25776185
TI  - Sleep disturbance associated with rotator cuff tear: correction with arthroscopic
      rotator cuff repair.
AB  - BACKGROUND: Sleep disturbance is a common complaint of patients with a rotator
      cuff tear. Inadequate and restless sleep, along with pain, is often a driving
      symptom for patients to proceed with rotator cuff repair. To date, no studies
      have examined sleep disturbance in patients undergoing rotator cuff repair, and
      there is no evidence that surgery improves sleep disturbance. HYPOTHESIS: Sleep
      disturbance is prevalent in patients with a symptomatic rotator cuff tear, and
      sleep disturbance improves after arthroscopic rotator cuff repair. STUDY DESIGN:
      Case series; Level of evidence, 4. METHODS: A total of 56 patients undergoing
      arthroscopic rotator cuff repair for full-thickness tears were enrolled in a
      prospective study. Patients were surveyed preoperatively and postoperatively at
      intervals of 2, 6, 12, 18, and 24 weeks. Patient outcomes were scored using the
      Pittsburgh Sleep Quality Index (PSQI), Simple Shoulder Test (SST), visual analog
      scale for pain (VAS), and single assessment numeric evaluation (SANE).
      Demographic and surgical factors were also collected for analysis. RESULTS:
      Preoperative PSQI scores indicative of sleep disturbance were reported in 89% of
      patients. After surgery, a statistically significant improvement in PSQI was
      achieved at 3 months (P = .0012; 91% follow-up) and continued through 6 months (P
      = .0179; 93% follow-up). Six months after surgery, only 38% of patients continued
      to have sleep disturbance. Multivariable linear regression of all surgical and
      demographic factors versus PSQI was performed and demonstrated that preoperative
      and prolonged postoperative narcotic use negatively affected sleep. CONCLUSION:
      Sleep disturbance is common in patients undergoing rotator cuff repair. After
      surgery, sleep disturbance improves to levels comparable with those of the
      general public. Preoperative and prolonged postoperative use of narcotic pain
      medication negatively affects sleep.

PMID- 25776186
TI  - Increased levels of symmetric dimethyl-arginine are associated with all-cause
      mortality in patients with symptomatic peripheral arterial disease.
AB  - OBJECTIVE: Recent interest has focused on the role of the methyl-arginines,
      endogenous inhibitors of nitric oxide, as adverse prognostic indicators. To date,
      few studies have assessed the role of symmetric dimethyl-arginine (SDMA) in
      patients with peripheral arterial disease. We aimed to determine the
      relationship, if any, of SDMA to all-cause mortality and disease severity as
      assessed by the ankle-brachial index (ABI) in patients with symptomatic
      peripheral arterial disease (PAD). METHODS: In 238 patients with symptomatic PAD
      and an ABI of <0.8, l-arginine, asymmetric dimethyl-arginine (ADMA) and SDMA
      levels were measured by hydrophilic-interaction liquid chromatography
      electrospray tandem mass spectrometry. RESULTS: The median follow-up was 6 years
      11 months (interquartile range [IQR], 4 years 5 months-7 years 10 months). SDMA
      and ADMA levels were higher in those who died compared with those who survived
      (0.51 [IQR, 0.44-0.66] MUmol/L vs 0.46 [IQR, 0.39-0.55] MUmol/L, P <= .001; and
      0.48 [IQR, 0.41-0.55] MUmol/L vs 0.45 [IQR, 0.39-0.50] MUmol/L, P = .007,
      respectively). l-arginine levels were similar in the two groups. On multivariate
      analysis, SDMA and ADMA as continuous variable were significantly associated with
      mortality (P = .001). For SDMA and ADMA, the highest compared with the lowest
      quartile levels were significantly associated with mortality (SDMA: hazard ratio,
      3.855; 95% confidence interval, 1.625-9.143; P = .002; ADMA: hazard ratio, 2.277;
      95% confidence interval, 1.114-4.654; P = .024). ADMA and SDMA showed a negative
      correlation with severity of PAD as assessed by ABI (r = -0.236, N = 216, P <
      .001; r = -0.209, N = 208, P = .002, respectively). CONCLUSIONS: The novel
      finding of this study is that SDMA levels were predictive of all cause-mortality
      and correlated with disease severity. Further studies should assess the role of
      nitric oxide donors in patients with high levels of SDMA.

PMID- 25776187
TI  - Assessing internal carotid artery stenosis with a semiautomated computed
      tomography angiography tool and duplex ultrasound.
AB  - OBJECTIVE: Duplex ultrasound (DUS) and computed tomography angiography (CTA) are
      both used as first-line noninvasive methods to investigate patients for internal
      carotid artery (ICA) disease. Although manual assessment of CTA is well
      established, semiautomated vessel analysis programs have yet to prove their
      clinical benefit. We compared one such vessel analysis program (TeraRecon, Foster
      City, Calif) with DUS. METHODS: A total of 85 arteries in 50 patients (35 men, 15
      women; mean age, 73 +/- 10 years) were eligible for comparison with the North
      American Symptomatic Carotid Endarterectomy Trial method. Duplex scanning
      comprised stenosis estimation based on (1) the intrastenotic and distal ICA
      diameter measurements on color-coded imaging (CCI), (2) the application of German
      Society for Ultrasound in Medicine (DEGUM) criteria (intrastenotic peak systolic
      velocity [PSV] >= 2 00 cm/s indicates 50% stenosis; intrastenotic PSV >= 300 cm/s
      together with a PSV of >= 50 cm/s in the distal ICA indicates 70% stenosis), and
      (3) the application of the University of Washington stenosis criteria (>= 50%
      stenosis is indicated by PSV >125 cm/s and end-diastolic velocity <140 cm/s; >=
      80% stenosis is indicated by PSV >125 cm/s and end-diastolic velocity >= 140
      cm/s). The minimum and maximum diameters at the stenosis site and at the distal
      reference ICA were automatically measured with the CTA vessel analysis tool. In
      addition, automated tracking generated corresponding cross-sectional areas at
      these two sites. Angiographic stenosis was then calculated using the minimum
      diameter (CTAmin), the average of the minimum and maximum diameters (CTAavg), and
      the areas (CTAarea) at both sites. RESULTS: Compared with duplex CCI, the three
      CTA modalities exhibited only a moderate agreement in terms of regression
      analysis (R(2) = 0.41-0.54) and Bland-Altman analysis (the standard deviation of
      the stenosis differences was >20%). In terms of sensitivity, specificity,
      positive predictive value, negative predictive value, and accuracy, DEGUM
      stenosis graduation was best balanced by duplex CCI (50% stenosis: 100%, 93%,
      85%, 100%, 95%; 70% stenosis: 71%, 100%, 100%, 97%, 98%) followed by CTAarea (50%
      stenosis: 80%, 73%, 54%, 90%, 75%; 70% stenosis: 66%, 94%, 55%, 96%, 96%).
      University of Washington stenosis was best balanced by duplex CCI followed by
      CTAarea. CONCLUSIONS: CTA analysis with a semiautomated vessel analysis tool
      provides variable results. Large discrepancies between methods in the degree of
      reported stenosis must be taken into consideration when CTA and DUS are used for
      clinical purposes. The semiautomated software tools need further improvements.

PMID- 25776188
TI  - Race as a predictor of delay from diagnosis to endarterectomy in clinically
      significant carotid stenosis.
AB  - OBJECTIVE: Prompt carotid endarterectomy (CEA) in clinically significant carotid
      stenosis is important in the prevention of neurologic sequelae. The greatest
      benefit from surgery is obtained by prompt revascularization on diagnosis. It has
      been demonstrated that black patients both receive CEA less frequently than white
      patients do and experience worse postoperative outcomes. We sought to test our
      hypothesis that black race is an independent risk factor for a prolonged time
      from sonographic diagnosis of carotid stenosis warranting surgery to the day of
      operation (TDO). METHODS: From 1998 to 2013 at a single institution, 166 CEA
      patients were retrospectively reviewed using Synthetic Derivative, a de
      identified electronic medical record. Factors potentially affecting TDO,
      including demographics, preoperative cardiac stress testing, degree of stenosis,
      smoking status, and comorbidities, were noted. Multivariate analysis was
      performed on variables that trended with prolonged TDO on univariate analysis (P
      < .10) to determine independent (P < .05) predictors of TDO. Subgroup analyses
      were further performed on the symptomatic and asymptomatic stenosis cohorts.
      RESULTS: There were 32 black patients and 134 white patients studied; the mean
      TDO was 78 +/- 17 days vs 33 +/- 3 days, respectively (P < .001). In addition to
      the need for preoperative cardiac stress testing, black race was the only
      variable that demonstrated a trend with (P < .10) or was an independent risk
      factor for (P < .05) prolonged TDO among all patients (B = 42 days; P < .001) and
      within the symptomatic (B = 35 days; P = .08) and asymptomatic (B = 35 days; P =
      .003) cohorts. On Kaplan-Meier analysis, black patients in each stratum of
      symptomatology (all, symptomatic, and asymptomatic patients) experienced
      prolonged TDO (log-rank, P < .03 for all three groups). CONCLUSIONS: Black race
      is a risk factor for a temporal delay in CEA for carotid stenosis. Awareness of
      this disparity may help surgeons avoid undesirable delays in operation for their
      black patients.

PMID- 25776189
TI  - Electrophysiological evidence of separate pathways for the perception of depth
      and 3D objects.
AB  - Previous studies have investigated the neural mechanism of 3D perception, but the
      neural distinction between 3D-objects and depth processing remains unclear. In
      the present study, participants viewed three types of graphics (planar graphics,
      perspective drawings, and 3D objects) while event-related potentials (ERP) were
      recorded. The ERP results revealed the following: (1) 3D objects elicited a
      larger and delayed N1 component than the other two types of stimuli; (2) during
      the P2 time window, significant differences between 3D objects and the
      perspective drawings were found mainly over a group of electrode sites in the
      left lateral occipital region; and (3) during the N2 complex, differences between
      planar graphics and perspective drawings were found over a group of electrode
      sites in the right hemisphere, whereas differences between perspective drawings
      and 3D objects were observed at another group of electrode sites in the left
      hemisphere. These findings support the claim that depth processing and object
      identification might be processed by separate pathways and at different
      latencies. 

PMID- 25776190
TI  - Back-stepping active disturbance rejection control design for integrated missile
      guidance and control system via reduced-order ESO.
AB  - This paper proposes a novel composite integrated guidance and control (IGC) law
      for missile intercepting against unknown maneuvering target with multiple
      uncertainties and control constraint. First, by using back-stepping technique,
      the proposed IGC law design is separated into guidance loop and control loop. The
      unknown target maneuvers and variations of aerodynamics parameters in guidance
      and control loop are viewed as uncertainties, which are estimated and compensated
      by designed model-assisted reduced-order extended state observer (ESO). Second,
      based on the principle of active disturbance rejection control (ADRC), enhanced
      feedback linearization (FL) based control law is implemented for the IGC model
      using the estimates generated by reduced-order ESO. In addition, performance
      analysis and comparisons between ESO and reduced-order ESO are examined.
      Nonlinear tracking differentiator is employed to construct the derivative of
      virtual control command in the control loop. Third, the closed-loop stability for
      the considered system is established. Finally, the effectiveness of the proposed
      IGC law in enhanced interception performance such as smooth interception course,
      improved robustness against multiple uncertainties as well as reduced control
      consumption during initial phase are demonstrated through simulations. 

PMID- 25776191
TI  - Structure of a new pseudaminic acid-containing capsular polysaccharide of
      Acinetobacter baumannii LUH5550 having the KL42 capsule biosynthesis locus.
AB  - The capsular polysaccharide from Acinetobacter baumannii LUH5550 was studied by
      1D and 2D (1)H and (13)C NMR spectroscopy. The following structure of the
      branched trisaccharide repeating unit was established: [structure: see text]
      where Pse5Ac7RHb indicates 5-acetamido-3,5,7,9-tetradeoxy-7-[(R)-3
      hydroxybutanoylamino]-L-glycero-L-manno-non-2-ulosonic acid. The genes in the
      capsule biosynthesis locus designated KL42 are consistent with the structure
      established.

PMID- 25776192
TI  - A phase I study of midostaurin and azacitidine in relapsed and elderly AML
      patients.
AB  - BACKGROUND: Midostaurin is a novel, orally available Fms-like tyrosine kinase 3
      (FLT3) tyrosine kinase inhibitor that induces cell cycle arrest and apoptosis of
      leukemic cells expressing mutant and wild type FLT3 receptors, and has shown
      potential synergism with cytotoxic chemotherapy. PATIENTS AND METHODS: We
      conducted a phase I study of azacitidine (intravenous 75 mg/m(2) daily for 7
      days) with escalating doses of oral midostaurin (25 mg twice per day [b.i.d.], 50
      mg b.i.d., and 75 mg b.i.d.) on days 8 to 21 of a 28-day cycle in untreated acute
      myeloid leukemia (AML) in older patients and/or relapsed AML. Patients were
      eligible regardless of FLT3 mutation status. Trough blood samples for
      pharmacokinetics were obtained on days 8, 15, and 21 before midostaurin dosing.
      RESULTS: Seventeen patients with a median age of 73 (range, 57-83) years were
      enrolled; 5 patients had previous conventional treatment and none of the patients
      had FLT3 mutations. Dose-limiting toxicities were not observed. Hospitalizations,
      primarily for infections, occurred in one-third of treatment cycles. Fourteen
      patients were evaluable for response: 3 attained complete remission and 2 had
      hematologic improvement. Median (range) survival from enrollment was 6 (1 to >=
      19) months. Three patients died within 60 days of enrollment (2 progressive
      disease, 1 non-dose-limiting toxicity, treatment-related). Pharmacokinetic data
      at 75 mg orally b.i.d. showed increased trough levels of midostaurin during cycle
      2 compared with cycle 1 and persistent and increasing levels of its active
      metabolite, CGP52421. CONCLUSION: The combination of sequential azacitidine and
      midostaurin is safe and tolerable with response rates comparable with azacitidine
      alone and should be studied further in FLT3 mutation-positive AML.

PMID- 25776193
TI  - A phase I study of targeted, dose-escalated intravenous busulfan in combination
      with etoposide as myeloablative therapy for autologous stem cell transplantation
      in acute myeloid leukemia.
AB  - BACKGROUND: Busulfan and etoposide have been used as myeloablative therapy for
      autologous hematopoietic stem cell transplantation (HSCT) in adults with acute
      myeloid leukemia (AML) for > 20 years. The use of targeted intravenous (I.V.)
      busulfan has significantly improved the tolerability and efficacy of this
      regimen. We designed a dose-escalation study to examine the maximum tolerated
      dose (MTD) of targeted I.V. busulfan with bolus etoposide as preparative therapy
      for autologous HSCT in AML. PATIENTS AND METHODS: In this single-center, phase I
      study, adult AML patients received I.V. busulfan targeted to either an area under
      the curve (AUC) of 1250 (cohort 1) or 1400 (cohort 2) MUmol/min over 16 doses.
      Dose adjustments based on plasma pharmacokinetics occurred before doses 2 and 11.
      Etoposide 60 mg/kg I.V. was administered 24 hours after the last busulfan dose
      and 3 days before stem cell infusion. RESULTS: Twelve patients with intermediate
      risk AML in first complete remission were treated. All patients in cohort 1 and 5
      patients (83%) in cohort 2 were within 10% of the target AUC. The MTD was not
      reached, although Grade >= 3 mucositis occurred in 3 patients (50%) in cohort 1
      and in 4 patients (66%) in cohort 2, limiting further dose escalation. Two-year
      relapse-free survival was 33% in cohort 1 versus 67% in cohort 2 (P = .08).
      CONCLUSION: Etoposide and targeted, dose-escalated I.V. busulfan as myeloablative
      therapy for autologous HSCT in AML is safe, with mucositis being the most
      significant toxicity. A phase II study is warranted to further evaluate the
      activity and safety of busulfan targeted to AUC 1400 MUmol/min.

PMID- 25776194
TI  - Validation of a Commercially Available Screening Tool for the Rapid
      Identification of CGG Trinucleotide Repeat Expansions in FMR1.
AB  - Recently developed PCR-based methods for fragile X syndrome testing are often
      regarded as screening tools because of a reduced reliance on Southern blot
      analysis. However, existing PCR methods rely essentially on capillary
      electrophoresis for the analysis of amplicons. These methods not only require an
      expensive capillary electrophoresis instrument but also involve post-PCR
      processing steps. Here, we evaluated a commercially available PCR-based assay
      that uses melt curve analysis as a screening tool for the rapid detection of CGG
      repeat expansions in the fragile X mental retardation 1 (FMR1) gene. On the basis
      of testing with well-characterized DNA samples, the assay gave a detection limit
      of 10 ng per reaction and an analytic specificity beyond 150 ng per reaction.
      Furthermore, the melt temperatures critical for result interpretation were found
      to be closely linked to the CGG expansion lengths with great consistency (CV <
      0.55%). The clinical performance of the assay was established with 528 blinded
      and previously analyzed clinical samples, yielding results of 100% sensitivity
      (95% CI, 91.0%-100%) and 99.6% specificity (95% CI, 98.5%-99.9%) in detecting
      expansions >55 CGG repeats in FMR1. This new approach eliminates post-PCR
      handling for all non-expanded samples, and exemplifies a truly efficient
      screening procedure. 

PMID- 25776195
TI  - [Working conditions, stress and burnout of Belgian professionals in radiotherapy:
      Comparative analysis and emotional labor exploration].
AB  - PUPOSE: This national survey aims, on the one hand, to perform a comparative
      analysis of working conditions, job strain and burnout of Belgian nurses,
      physicists and radiation oncologists working in radiotherapy and, on the other
      hand, to explore the role of emotional labor in the development of stress and
      burnout. METHODS: We used the Working Conditions and Control Questionnaire, the
      Positive and Negative Occupational States Inventory, the Maslach Burnout
      Inventory, the negative work-home interaction subscale of the Survey Work-Home
      Interaction Nijmegen (NEGWHI), Perceived Organizational Support Scale and
      Emotional Labor Scale. One open question asked about problematic job situations.
      RESULTS: Ninety-eight nurses and physicists participated (33 % response rate), in
      addition to 66 radiation oncologists from a previous study. Although global
      scores of working conditions, job strain and burnout corresponded to normal
      scores, comparative analysis identified physicists as focus group concerning job
      strain and burnout. Moreover, nurses and physicists surface acting was a good
      predictor of job strain (beta=0.22, P=0.01), emotional exhaustion (beta=0.32,
      P<0.001) and depersonalization (beta=0.43, P<0.001). Nevertheless, perceived
      organizational support was a moderator in this relation. CONCLUSION: Radiotherapy
      employees were in the norms. The importance of organizational support was
      demonstrated to avoid potential health problems, for workers experiencing high
      levels of emotional demands.

PMID- 25776196
TI  - Current developments in marine microbiology: high-pressure biotechnology and the
      genetic engineering of piezophiles.
AB  - A key aspect of marine environments is elevated pressure; for example, ~70% of
      the ocean is at a pressure of at least 38MPa. Many types of Bacteria and Archaea
      reside under these high pressures, which drive oceanic biogeochemical cycles and
      catalyze reactions among rocks, sediments and fluids. Most marine prokaryotes are
      classified as piezotolerant or as (obligate)-piezophiles with few cultivated
      relatives. The biochemistry and physiology of these organisms are largely
      unknown. Recently, high-pressure cultivation technology has been combined with
      omics and DNA recombination methodologies to examine the physiology of
      piezophilic marine microorganisms. We are now beginning to understand the
      adaptive mechanisms of these organisms, along with their ecological functions and
      evolutionary processes. This knowledge is leading to the further development of
      high-pressure-based biotechnology. 

PMID- 25776197
TI  - Differences in Prognostic Factors and Failure Patterns Between Invasive
      Micropapillary Carcinoma and Carcinoma With Micropapillary Component Versus
      Invasive Ductal Carcinoma of the Breast: Retrospective Multicenter Case-Control
      Study (KROG 13-06).
AB  - PURPOSE: We designed the present study to investigate differences in prognostic
      factors and failure patterns between patients with invasive micropapillary
      carcinoma or carcinoma with micropapillary component (IMPC) and randomly matched
      patients with invasive ductal carcinoma (IDC) of the breast at multiple
      institutions of the Korean Radiation Oncology Group (KROG). MATERIALS AND
      METHODS: This retrospective multicenter study was performed using subjects
      treated from January 1999 to November 2011. Female patients who had undergone
      curative resection for breast cancer without neoadjuvant chemotherapy were
      considered for this study. Exact matches were made for age (+/- 3 years),
      pathologic tumor and node stage, treatment method (surgery with or without
      radiotherapy), and period when surgery was performed (within 1 year) at the same
      institution. RESULTS: A total of 534 patients were analyzed. The median follow-up
      period was 59 months in both groups. In the comparison of clinicopathologic
      characteristics, rates of lymphovascular invasion (LVI) and nuclear grade III
      were both significantly higher in IMPC than in IDC (P < .001, P = .01,
      respectively). During the follow-up period, recurrences developed in 40 patients
      with IMPC (15.0%) and 21 with IDC (7.9%). Locoregional recurrence (LRR) developed
      in 22 patients with IMPC (8.2%) and 10 with IDC (3.7%). The rate of distant
      metastasis did not differ between the 2 groups (P = .52). LRR-free survival (P =
      .03) and recurrence-free survival (P = .007) were significantly different between
      the 2 groups, but overall survival was not (P = .67). CONCLUSION: IMPC is
      associated with a higher rate of LVI, high nuclear grade, and a propensity for
      LRR compared to IDC. Modification of the locoregional treatment modality might be
      needed in this pathologic subtype of breast cancer.

PMID- 25776198
TI  - A Prospective Study to Assess the Feasibility of Axillary Reverse Mapping and
      Evaluate Its Effect on Preventing Lymphedema in Breast Cancer Patients.
AB  - BACKGROUND: The axillary reverse mapping (ARM) procedure can distinguish
      lymphatics draining the arm from those draining the breast. It has been proposed
      to preserve lymphatic drainage of the upper limbs and reduce the incidence of
      upper limb lymphedema during breast cancer surgery. The aim of our study was to
      assess the feasibility of ARM in modified radical mastectomy and to evaluate its
      effect on prevention of lymphedema. PATIENTS AND METHODS: From January 2012 to
      March 2014, a prospective study was performed in 265 breast cancer patients who
      underwent modified radical mastectomy. Patients were divided into 2 groups, 127
      patients (47.93%, control group) received a traditional axillary lymph node
      dissection (ALND), and 138 patients (52.07%, experimental group) received ARM
      preservation of the nodes and lymphatics during ALND. Radioactive tracer and
      methylene blue were used for ARM of the nodes and lymphatics. All of the
      identified ARM nodes were diagnosed using fine needle aspiration cytology for
      assessment of metastatic status. All resected axillary lymph nodes were conducted
      in a pathology examination to evaluate tumor metastasis. Data were collected on
      variations in identification of the ARM nodes and lymphatics, the metastasis of
      ARM nodes, and the occurrence of lymphedema. RESULTS: In the experimental group,
      the ARM procedure was successfully conducted in 129 cases (93.48%). ARM nodes
      metastasis occurred in 11 patients (8.53%). The median follow-up time was 20
      months, at the last evaluation there were 42 patients who developed upper limb
      lymphedema in the control group (33.07%), and in the experimental group the
      incidence of lymphedema was 5.93% (7/118; P < .001). None of the patients had
      nodal relapses during the follow-up time. CONCLUSION: ARM appears to be a
      feasible technique with which to identify upper arm nodes and lymphatics during
      the modified radical mastectomy procedure. The incidence of lymphedema can be
      decreased in patients with use of the ARM procedure.

PMID- 25776199
TI  - A randomised, double-blind, four-way, crossover trial comparing the 24-h FEV1
      profile for once-daily versus twice-daily treatment with olodaterol, a novel long
      acting beta2-agonist, in patients with chronic obstructive pulmonary disease.
AB  - BACKGROUND: This randomised, double-blind, four-way, crossover, Phase II study
      compared the 24-h forced expiratory volume in 1 s (FEV1) profile of alternative
      dosing frequencies of two total daily doses of olodaterol (5 and 10 MUg) in
      patients with chronic obstructive pulmonary disease (COPD). METHODS: Patients
      received olodaterol 2 MUg twice daily (BID), 5 MUg BID, 5 MUg once daily (QD) and
      10 MUg QD in a randomised sequence over 3-week treatment periods. Co-primary end
      points were FEV1 area under the curve from 0 to 12 h (AUC0-12) and area under the
      curve from 12 to 24 h (AUC12-24) responses. Additional lung-function responses,
      pharmacokinetics and safety were assessed. RESULTS: 47 patients were treated. All
      olodaterol doses provided significant increases in FEV1 versus baseline (p <
      0.001) and FEV1 time profiles were nearly identical for olodaterol 5 and 10 MUg
      QD. Olodaterol 5 MUg QD demonstrated improved FEV1 AUC0-12 and similar AUC12-24
      versus 2 MUg BID. Olodaterol 5 MUg QD showed slightly increased FEV1 AUC0-12 but
      lower AUC12-24 compared to 5 MUg BID. Bronchodilation over 24 h was similar for
      olodaterol 5 MUg QD and BID. All doses were well tolerated. CONCLUSIONS:
      Olodaterol 5 MUg QD is efficacious in COPD, with a superior bronchodilatory
      profile compared to 2 MUg BID, which is close to the same total daily dose, and a
      similar degree of bronchodilation over 24 h compared with double the daily dose
      (administered as 10 MUg QD or 5 MUg BID). TRIAL REGISTRATION: ClinicalTrials.gov:
      NCT00846768.

PMID- 25776200
TI  - Risk of Reactivation of Hepatitis B Virus Infection in Psoriasis Patients Treated
      With Biologics: A Retrospective Analysis of 20 Cases From the BIOBADADERM
      Database.
AB  - INTRODUCTION AND OBJECTIVES: A 5% risk of reactivation of hepatitis B virus (HBV)
      infection has been reported in patients with diseases other than psoriasis
      treated with tumor necrosis factor inhibitors. The aim of this study was to
      investigate the risk of HBV reactivation in patients with a past history of HBV
      infection who were receiving biologic therapy for psoriasis. MATERIAL AND
      METHODS: This was a multicenter study of 20 patients with psoriasis who were
      treated with at least 1 biologic agent. All the patients had serologic evidence
      of past HBV infection (positive total hepatitis B core antibody and negative
      hepatitis B surface antibody). We analyzed the clinical, serological, and liver
      function variables recorded before, during, and at the end of follow-up. The
      viral load at the end of follow-up was also analyzed for all patients. RESULTS:
      None of the patients fulfilled the criteria for HBV reactivation at the end of a
      median follow-up period of 40 months. Combining our data with data from other
      studies of psoriasis patients with a past history of HBV infection who were
      treated with a biologic, we calculated a maximum estimated risk of HBV
      reactivation for a mean follow-up period of 30 months of 2.7 reactivations per
      100 patients. CONCLUSIONS: Biologic therapy did not cause HBV reactivation in our
      series of patients. Nonetheless, because of the potentially serious complications
      associated with HBV reactivation, it is important to measure viral load in
      patients with a history of HBV infection prior to initiation of biologic therapy
      to rule out occult carriage. These patients should also be monitored regularly in
      conjunction with a hepatologist.

PMID- 25776201
TI  - The multigene family of fungal laccases and their expression in the white rot
      basidiomycete Flammulina velutipes.
AB  - Fungal laccases play important roles in matrix degradation. Eleven laccase genes,
      including three novel ones (designated lac1, lac2 and lac4) were identified after
      sequencing the entire genome of the edible, white-rot fungus Flammulina
      velutipes. Analysis using bioinformatics revealed that all of the laccases,
      except lac3, possess a signal peptide. These laccase proteins consist of 502-670
      amino acids and have predicted molecular weights ranging from 55kDa to 74kDa.
      These proteins each contain four copper-binding sites, except for Lac10.
      Transcriptomes were sequenced at different developmental stages and in different
      fruiting body tissues to analyze if there was differential expression of laccase
      genes. The novel laccase gene lac4 exhibited the highest expression levels among
      all of the observed laccases at every developmental stage and in all fruiting
      body tissues examined. We conclude that laccases in F. velutipes play a role not
      only in lignin degradation, but also in fruiting body formation and development.

PMID- 25776202
TI  - Methods for estimating uncertainty in PMF solutions: examples with ambient air
      and water quality data and guidance on reporting PMF results.
AB  - The new version of EPA's positive matrix factorization (EPA PMF) software, 5.0,
      includes three error estimation (EE) methods for analyzing factor analytic
      solutions: classical bootstrap (BS), displacement of factor elements (DISP), and
      bootstrap enhanced by displacement (BS-DISP). These methods capture the
      uncertainty of PMF analyses due to random errors and rotational ambiguity. To
      demonstrate the utility of the EE methods, results are presented for three data
      sets: (1) speciated PM2.5 data from a chemical speciation network (CSN) site in
      Sacramento, California (2003-2009); (2) trace metal, ammonia, and other species
      in water quality samples taken at an inline storage system (ISS) in Milwaukee,
      Wisconsin (2006); and (3) an organic aerosol data set from high-resolution
      aerosol mass spectrometer (HR-AMS) measurements in Las Vegas, Nevada (January
      2008). We present an interpretation of EE diagnostics for these data sets,
      results from sensitivity tests of EE diagnostics using additional and fewer
      factors, and recommendations for reporting PMF results. BS-DISP and BS are found
      useful in understanding the uncertainty of factor profiles; they also suggest if
      the data are over-fitted by specifying too many factors. DISP diagnostics were
      consistently robust, indicating its use for understanding rotational uncertainty
      and as a first step in assessing a solution's viability. The uncertainty of each
      factor's identifying species is shown to be a useful gauge for evaluating
      multiple solutions, e.g., with a different number of factors. 

PMID- 25776203
TI  - Magnetic resonance enterography in post-operative inflammatory bowel disease.
AB  - OBJECTIVE: To describe the role of magnetic resonance enterography (MRE) in
      patients with inflammatory bowel disease (IBD), and to review the expected post
      operative appearance, as well as, potential surgical complications in this unique
      patient population. CONCLUSION: MRE compares favorably to CT Enterography (CTE)
      in terms of overall diagnostic accuracy and may provide better functional
      assessment of the small bowel through cine-MRI, diffusion-weighted imaging and
      dynamic contrast-enhancement. In the post-operative population, MRE provides
      critical information including: normal post-surgical anatomy, chronic strictures
      vs. active inflammation and disease/treatment-related complications. The post
      operative IBD patient undergoes frequent repeated imaging and MRE may
      significantly reduce cumulative radiation dose while providing similar or
      improved diagnostic accuracy compared to CTE. MRE should be considered as an
      alternative imaging modality in this population.

PMID- 25776204
TI  - The wall-echo-shadow (WES) sign.

PMID- 25776205
TI  - Quantitative characterizations of ultrashort echo (UTE) images for supporting air
      bone separation in the head.
AB  - Accurate separation of air and bone is critical for creating synthetic CT from
      MRI to support Radiation Oncology workflow. This study compares two different
      ultrashort echo-time sequences in the separation of air from bone, and evaluates
      post-processing methods that correct intensity nonuniformity of images and
      account for intensity gradients at tissue boundaries to improve this
      discriminatory power. CT and MRI scans were acquired on 12 patients under an
      institution review board-approved prospective protocol. The two MRI sequences
      tested were ultra-short TE imaging using 3D radial acquisition (UTE), and using
      pointwise encoding time reduction with radial acquisition (PETRA). Gradient
      nonlinearity correction was applied to both MR image volumes after acquisition.
      MRI intensity nonuniformity was corrected by vendor-provided normalization
      methods, and then further corrected using the N4itk algorithm. To overcome the
      intensity-gradient at air-tissue boundaries, spatial dilations, from 0 to 4 mm,
      were applied to threshold-defined air regions from MR images. Receiver operating
      characteristic (ROC) analyses, by comparing predicted (defined by MR images)
      versus 'true' regions of air and bone (defined by CT images), were performed with
      and without residual bias field correction and local spatial expansion. The post
      processing corrections increased the areas under the ROC curves (AUC) from 0.944
      +/- 0.012 to 0.976 +/- 0.003 for UTE images, and from 0.850 +/- 0.022 to 0.887 +/
      0.012 for PETRA images, compared to without corrections. When expanding the
      threshold-defined air volumes, as expected, sensitivity of air identification
      decreased with an increase in specificity of bone discrimination, but in a non
      linear fashion. A 1 mm air mask expansion yielded AUC increases of 1 and 4% for
      UTE and PETRA images, respectively. UTE images had significantly greater
      discriminatory power in separating air from bone than PETRA images. Post
      processing strategies improved the discriminatory power of air from bone for both
      UTE and PETRA images, and reduced the difference between the two imaging
      sequences. Both post-processed UTE and PETRA images demonstrated sufficient power
      to discriminate air from bone to support synthetic CT generation from MRI data. 

PMID- 25776206
TI  - Calcaneal spurs among San and Khoi skeletons.
AB  - Only few studies considered the prevalence of calcaneal enthesophytes commonly
      called heel spurs among historic skeleton samples. In the present study the
      frequency of plantar calcaneal spurs among 54 19(th) century Khoisan skeletons
      was analyzed. Five individuals (9.6 %) had a plantar calcaneal spur at the right
      side or left side. Calcaneal spurs were more likely to occur in older
      individuals. More than 20 % of the individuals aged between 40 and 60 years
      (mature) showed plantar spurs, while 6.2 % of the individuals aged between 20 and
      40 years had plantar spurs; however this difference was not significant. No sex
      differences were present in the prevalence of calcaneal spurs. Male and female
      individuals did not differ in the metric dimensions of the calcanceal spurs
      significantly. 

PMID- 25776207
TI  - [Communication with children: practical hints and tools for the anesthesiology
      routine].
AB  - BACKGROUND: Pediatric patients represent a special challenge both for the
      management of anesthesia and for communication, especially the anxious and
      screaming child. Children have specific features of fears, cognition,
      comprehension and skills depending on the stage of development. In addition,
      behavior and anxiety are strongly shaped by the parents who have to be
      incorporated. AIM: This article presents the special features of children as well
      as practical strategies and aids for dealing with children in a perioperative
      setting. MATERIAL AND METHODS: In children suggestibility and susceptibility to
      placebo and nocebo effects are increased. This makes them more sensitive to
      negative factors but can also be utilized for positive, constructive effects.
      Possibilities are presented which make use of the special characteristics of
      children. A number of examples from daily clinical routine are given. RESULTS: A
      child's imagination, creativity and capability for dissociation in particular
      allow an effective application of indirect suggestion, metaphors, stories,
      changes in focus of attention, retreat to an inner or imagined safe place,
      reframing of disturbing noises and events, pacing and leading in small steps and
      an activation of inner resources. A hand puppet, a pet toy, a little magic trick,
      introducing a magic friend, acupoint for palpitations with self-affirmation,
      stick figure drawings, ceiling pictures or holding hands can be quite helpful.
      All medical devices and interventions can be explained in a way that children can
      understand and in positive statements without lying or neglecting the need for
      information. CONCLUSION: Meeting at eye level, talking to the child instead of
      just about it, a language appropriate for children but not childish,
      comprehensible information and explanations, return of control and care more than
      pure technical distance, all play an important role. A serious look into such
      communication strategies can help the anesthetist to overcome uncertainties that
      a child can easily sense.

PMID- 25776208
TI  - [Telemedicine: stopgap or future concept?].

PMID- 25776209
TI  - [Protoplasm, coagulation and colloids : Forgotten chapter in the research history
      of anesthesia between Zeitgeist and paradigm].
AB  - The historically most important mechanistic theories attributed the fundamental
      cause of anesthesia to interactions betweeen anesthetics and proteins as early as
      the 1870s. According to the underlying thought, the resulting changes in the
      consistency of cellular protoplasm were the cause of the anesthetized state of
      the whole organism.These protoplasm coagulation theories, as they were
      collectively referred to, brought the contemporary enthusiasm for protoplasm, the
      rapid advances in colloid chemistry and the unified theory of narcosis proclamed
      by Claude Bernard under a unified mechanistic theory that reflected the Zeitgeist
      of the epoch.This research effort, on the intersection of the developing
      disciplines of cellular biology and colloid chemistry, lasted for almost a
      century. It involved scientists of worldwide reputation and resulted in a number
      of elegant theories. Contrary to widespread opinion, proteins and not lipids were
      recognized and investigated first as the critical molecular target of anesthetics
      more than a century prior to their much publicized rediscovery in 1984.The
      protoplasm coagulation theories of anesthesia were pursued after the First World
      War across ideological trenches by scientists in Europe, the Soviet Union and the
      United States. They united research in anesthesia with research of fundamental
      cell biology.In contrast to the much less fruitful lipid theories, protoplasm
      coagulation theories are largely forgotten without leaving a trace in
      contemporary discussions of the history of anesthesia. For many tyears, however,
      they constituted an essential part of fundamental anesthetic research and must
      therefore be mentioned in any historical review. 

PMID- 25776210
TI  - Neural activation in speech production and reading aloud in native and non-native
      languages.
AB  - We used fMRI to investigate neural activation in reading aloud in bilinguals
      differing in age of acquisition. Three groups were compared: French-English
      bilinguals who acquired two languages from birth (simultaneous), French-English
      bilinguals who learned their L2 after the age of 5 years (sequential), and
      English-speaking monolinguals. While the bilingual groups contrasted in age of
      acquisition, they were matched for language proficiency, although sequential
      bilinguals produced speech with a less native-like accent in their L2 than in
      their L1. Simultaneous bilinguals activated similar brain regions to an
      equivalent degree when reading in their two languages. In contrast, sequential
      bilinguals more strongly activated areas related to speech-motor control and
      orthographic to phonological mapping, the left inferior frontal gyrus, left
      premotor cortex, and left fusiform gyrus, when reading aloud in L2 compared to
      L1. In addition, the activity in these regions showed a significant positive
      correlation with age of acquisition. The results provide evidence for the
      engagement of overlapping neural substrates for processing two languages when
      acquired in native context from birth. However, it appears that the maturation of
      certain brain regions for both speech production and phonological encoding is
      limited by a sensitive period for L2 acquisition regardless of language
      proficiency.

PMID- 25776212
TI  - Gradient-free MCMC methods for dynamic causal modelling.
AB  - In this technical note we compare the performance of four gradient-free MCMC
      samplers (random walk Metropolis sampling, slice-sampling, adaptive MCMC sampling
      and population-based MCMC sampling with tempering) in terms of the number of
      independent samples they can produce per unit computational time. For the
      Bayesian inversion of a single-node neural mass model, both adaptive and
      population-based samplers are more efficient compared with random walk Metropolis
      sampler or slice-sampling; yet adaptive MCMC sampling is more promising in terms
      of compute time. Slice-sampling yields the highest number of independent samples
      from the target density - albeit at almost 1000% increase in computational time,
      in comparison to the most efficient algorithm (i.e., the adaptive MCMC sampler). 

PMID- 25776211
TI  - Distinct neural representations of placebo and nocebo effects.
AB  - Expectations shape the way we experience the world. In this study, we used fMRI
      to investigate how positive and negative expectation can change pain experiences
      in the same cohort of subjects. We first manipulated subjects' treatment
      expectation of the effectiveness of three inert creams, with one cream labeled
      "Lidocaine" (positive expectancy), one labeled "Capsaicin" (negative expectancy)
      and one labeled "Neutral" by surreptitiously decreasing, increasing, or not
      changing respectively, the intensity of the noxious stimuli administered
      following cream application. We then used fMRI to investigate the signal changes
      associated with administration of identical pain stimuli before and after the
      treatment and control creams. Twenty-four healthy adults completed the study.
      Results showed that expectancy significantly modulated subjective pain ratings.
      After controlling for changes in the neutral condition, the subjective pain
      rating changes evoked by positive and negative expectancies were significantly
      associated. fMRI results showed that the expectation of an increase in pain
      induced significant fMRI signal changes in the insula, orbitofrontal cortex, and
      periaqueductal gray, whereas the expectation of pain relief evoked significant
      fMRI signal changes in the striatum. No brain regions were identified as common
      to both "Capsaicin" and "Lidocaine" conditioning. There was also no significant
      association between the brain response to identical noxious stimuli in the pain
      matrix evoked by positive and negative expectancies. Our findings suggest that
      positive and negative expectancies engage different brain networks to modulate
      our pain experiences, but, overall, these distinct patterns of neural activation
      result in a correlated placebo and nocebo behavioral response. 

PMID- 25776213
TI  - MR-based attenuation correction for PET/MRI neurological studies with continuous
      valued attenuation coefficients for bone through a conversion from R2* to CT
      Hounsfield units.
AB  - AIM: MR-based correction for photon attenuation in PET/MRI remains challenging,
      particularly for neurological applications requiring quantitation of data.
      Existing methods are either not sufficiently accurate or are limited by the
      computation time required. The goal of this study was to develop an MR-based
      attenuation correction method that accurately separates bone tissue from air and
      provides continuous-valued attenuation coefficients for bone. MATERIALS AND
      METHODS: PET/MRI and CT datasets were obtained from 98 subjects (mean age [+/
      SD]: 66yrs [+/-9.8], 57 females) using an IRB-approved protocol and with informed
      consent. Subjects were injected with 352+/-29MBq of (18)F-Florbetapir tracer, and
      PET acquisitions were begun either immediately or 50min after injection. CT
      images of the head were acquired separately using a PET/CT system. Dual echo
      ultrashort echo-time (UTE) images and two-point Dixon images were acquired.
      Regions of air were segmented via a threshold of the voxel-wise multiplicative
      inverse of the UTE echo 1 image. Regions of bone were segmented via a threshold
      of the R2* image computed from the UTE echo 1 and UTE echo 2 images. Regions of
      fat and soft tissue were segmented using fat and water images decomposed from the
      Dixon images. Air, fat, and soft tissue were assigned linear attenuation
      coefficients (LACs) of 0, 0.092, and 0.1cm(-1), respectively. LACs for bone were
      derived from a regression analysis between corresponding R2* and CT values. PET
      images were reconstructed using the gold standard CT method and the proposed CAR
      RiDR method. RESULTS: The RiDR segmentation method produces mean Dice
      coefficient+/-SD across subjects of 0.75+/-0.05 for bone and 0.60+/-0.08 for air.
      The CAR model for bone LACs greatly improves accuracy in estimating CT values
      (28.2%+/-3.0 mean error) compared to the use of a constant CT value (46.9%+/-5.8,
      p<10(-6)). Finally, the CAR-RiDR method provides a low whole-brain mean absolute
      percent-error (MAPE+/-SD) in PET reconstructions across subjects of 2.55%+/-0.86.
      Regional PET errors were also low and ranged from 0.88% to 3.79% in 24 brain
      ROIs. CONCLUSION: We propose an MR-based attenuation correction method (CAR-RiDR)
      for quantitative PET neurological imaging. The proposed method employs UTE and
      Dixon images and consists of two novel components: 1) accurate segmentation of
      air and bone using the inverse of the UTE1 image and the R2* image, respectively
      and 2) estimation of continuous LAC values for bone using a regression between
      R2* and CT-Hounsfield units. From our analysis, we conclude that the proposed
      method closely approaches (<3% error) the gold standard CT-scaled method in PET
      reconstruction accuracy.

PMID- 25776215
TI  - A prospective fMRI-based technique for localising the epileptogenic zone in
      presurgical evaluation of epilepsy.
AB  - There is growing evidence for the benefits of simultaneous EEG-fMRI as a non
      invasive localising tool in the presurgical evaluation of epilepsy. However, many
      EEG-fMRI studies fail due to the absence of interictal epileptic discharges
      (IEDs) on EEG. Here we present an algorithm which makes use of fMRI as sole
      modality to localise the epileptogenic zone (EZ). Recent studies using various
      model-based or data-driven fMRI analysis techniques showed that it is feasible to
      find activation maps which are helpful in the detection of the EZ. However, there
      is lack of evidence that these techniques can be used prospectively, due to (a)
      their low specificity, (b) selecting multiple activation maps, or (c) a
      widespread epileptic network indicated by the selected maps. In the current study
      we present a method based on independent component analysis and a cascade of
      classifiers that exclusively detects a single map related to interictal epileptic
      brain activity. In order to establish the sensitivity and specificity of the
      proposed method, it was evaluated on a group of 18 EEG-negative patients with a
      single well-defined EZ and 13 healthy controls. The results show that our method
      provides maps which correctly indicate the EZ in several (N=4) EEG-negative cases
      but at the same time maintaining a high specificity (92%). We conclude that our
      fMRI-based approach can be used in a prospective manner, and can extend the
      applicability of fMRI to EEG-negative cases.

PMID- 25776214
TI  - Bayesian segmentation of brainstem structures in MRI.
AB  - In this paper we present a method to segment four brainstem structures (midbrain,
      pons, medulla oblongata and superior cerebellar peduncle) from 3D brain MRI
      scans. The segmentation method relies on a probabilistic atlas of the brainstem
      and its neighboring brain structures. To build the atlas, we combined a dataset
      of 39 scans with already existing manual delineations of the whole brainstem and
      a dataset of 10 scans in which the brainstem structures were manually labeled
      with a protocol that was specifically designed for this study. The resulting
      atlas can be used in a Bayesian framework to segment the brainstem structures in
      novel scans. Thanks to the generative nature of the scheme, the segmentation
      method is robust to changes in MRI contrast or acquisition hardware. Using cross
      validation, we show that the algorithm can segment the structures in previously
      unseen T1 and FLAIR scans with great accuracy (mean error under 1mm) and
      robustness (no failures in 383 scans including 168 AD cases). We also indirectly
      evaluate the algorithm with a experiment in which we study the atrophy of the
      brainstem in aging. The results show that, when used simultaneously, the volumes
      of the midbrain, pons and medulla are significantly more predictive of age than
      the volume of the entire brainstem, estimated as their sum. The results also
      demonstrate that the method can detect atrophy patterns in the brainstem
      structures that have been previously described in the literature. Finally, we
      demonstrate that the proposed algorithm is able to detect differential effects of
      AD on the brainstem structures. The method will be implemented as part of the
      popular neuroimaging package FreeSurfer.

PMID- 25776216
TI  - Network-level reorganisation of functional connectivity following arm amputation.
AB  - One of the most striking demonstrations of plasticity in the adult human brain
      follows peripheral injury, such as amputation. In the primary sensorimotor
      cortex, arm amputation results in massive local remapping of the missing hands'
      cortical territory. However, little is known about the consequences of
      sensorimotor deprivation on global brain organisation. Here, we used resting
      state fMRI to identify large-scale reorganisation beyond the primary sensorimotor
      cortex in arm amputees, compared with two-handed controls. Specifically, we
      characterised changes in functional connectivity between the cortical territory
      of the missing hand in the primary sensorimotor cortex ('missing hand cortex')
      and two networks of interest: the sensorimotor network, which is typically
      strongly associated with the hand cortex, and the default mode network (DMN),
      which is normally dissociated from it. Functional connectivity values between the
      missing hand cortex and the sensorimotor network were reduced in amputees, and
      connectivity was weaker in individuals amputated for longer periods. Lower levels
      of functional coupling between the missing hand cortex and the sensorimotor
      network were also associated with emerged coupling of this cortex with the DMN.
      Our results demonstrate that plasticity following arm amputation is not
      restricted to local remapping occurring within the sensorimotor homunculus of the
      missing hand but rather produces a cascade of cortical reorganisation at a
      network-level scale. These findings may provide a new framework for understanding
      how local deprivation following amputation could elicit complex perceptual
      experiences of phantom sensations, such as phantom pain. 

PMID- 25776217
TI  - Association between neuroticism and amygdala responsivity emerges under stressful
      conditions.
AB  - Increased amygdala reactivity in response to salient stimuli is seen in patients
      with affective disorders, in healthy subjects at risk for these disorders, and in
      stressed individuals, making it a prime target for mechanistic studies into the
      pathophysiology of affective disorders. However, whereas individual differences
      in neuroticism are thought to modulate the effect of stress on mental health, the
      mechanistic link between stress, neuroticism and amygdala responsivity is
      unknown. Thus, we studied the relationship between experimentally induced stress,
      individual differences in neuroticism, and amygdala responsivity. To this end,
      fearful and happy faces were presented to a large cohort of young, healthy males
      (n=120) in two separate functional MRI sessions (stress versus control) in a
      randomized, controlled cross-over design. We revealed that amygdala reactivity
      was modulated by an interaction between the factors of stress, neuroticism, and
      the emotional valence of the facial stimuli. Follow-up analysis showed that
      neuroticism selectively enhanced amygdala responses to fearful faces in the
      stress condition. Thus, we show that stress unmasks an association between
      neuroticism and amygdala responsivity to potentially threatening stimuli. This
      effect constitutes a possible mechanistic link within the complex pathophysiology
      of affective disorders, and our novel approach appears suitable for further
      studies targeting the underlying mechanisms. 

PMID- 25776218
TI  - The neural correlates of sex differences in left-right confusion.
AB  - Difficulties in left-right discrimination (LRD) are commonly experienced in
      everyday life situations. Here we investigate the neurocognitive mechanisms of
      LRD and the specific role of left angular gyrus. Given that previous behavioral
      research reported women to be more susceptible to left-right confusion, the
      current study focuses particularly on the neural basis of sex differences in LRD
      while controlling for potential menstrual cycle effects (repeated measures
      design). 16 women and 15 men were presented pictures of pointing hands in various
      orientations (rotated versus non-rotated) and were asked to identify them as left
      or right hands. Results revealed that LRD was particularly associated with
      activation in inferior parietal regions, extending into the right angular gyrus.
      Irrespective of menstrual cycle phase, women, relative to men, recruited more
      prefrontal areas, suggesting higher top-down control in LRD. For the subset of
      rotated stimuli as compared to the non-rotated, we found leftward asymmetry for
      both men and women, although women scored significantly lower. We conclude that
      there are sex differences in the neurocognitive mechanisms underlying LRD.
      Although the angular gyrus is involved in LRD, several other parietal areas are
      at least as critical. Moreover, the hypothesis that more left-right confusion is
      due to more bilateral activation (in women) can be rejected.

PMID- 25776220
TI  - Sensitive fluorescence detection of lysozyme using a
      tris(bipyridine)ruthenium(II) complex containing multiple cyclodextrins.
AB  - A new series of photoactive metallocyclodextrins with increased fluorescence
      intensity upon binding with ssDNAs/aptamers has been demonstrated to sensitively
      and selectively detect lysozyme. The detection mechanism relies on the formation
      of an aptamer-lysozyme complex, which leads to reduction of fluorescence
      intensity. 

PMID- 25776221
TI  - Low-molecular-weight heparin protects kidney through an anti-apoptotic mechanism
      in a rat pre-eclamptic model.
AB  - OBJECTIVE: To investigate the effect of low-molecular-weight heparin (LMWH) for
      the treatment of pre-eclampsia (PE) and the underlying mechanism. STUDY DESIGN:
      PE was established in a rat model using l-NG-nitroarginine methyl ester (l-NAME).
      The effect of LMWH was examined by measuring various physiological parameters
      known to be associated with PE. RESULTS: Blood pressure, urinary protein, blood
      urea nitrogen and serum creatinine were higher in l-NAME-treated rats compared
      with control rats. In addition, the number of fetuses, and the weight of fetuses
      and placentas was lower in l-NAME-treated rats, indicating the establishment of
      PE conditions. Apoptosis was found in kidney tissue in l-NAME-treated rats. LMWH
      treatment restored the PE-associated disorders, and inhibited apoptosis in kidney
      tissue in these rats. CONCLUSIONS: LMWH can control PE conditions, protect renal
      function and improve fetal health. The mechanism of renal protection is likely to
      be related to the inhibitory effect of LMWH on apoptosis in kidney tissue. This
      study provides evidence that LMWH can potentially be used as a safe and effective
      anti-PE drug to improve PE conditions and protect renal function by inhibiting PE
      induced apoptosis.

PMID- 25776219
TI  - Evidence for an anterior-posterior differentiation in the human hippocampal
      formation revealed by meta-analytic parcellation of fMRI coordinate maps: focus
      on the subiculum.
AB  - Previous studies, predominantly in experimental animals, have suggested the
      presence of a differentiation of function across the hippocampal formation. In
      rodents, ventral regions are thought to be involved in emotional behavior while
      dorsal regions mediate cognitive or spatial processes. Using a combination of
      modeling the co-occurrence of significant activations across thousands of
      neuroimaging experiments and subsequent data-driven clustering of these data we
      were able to provide evidence of distinct subregions within a region
      corresponding to the human subiculum, a critical hub within the hippocampal
      formation. This connectivity-based model consists of a bilateral anterior region,
      as well as separate posterior and intermediate regions on each hemisphere.
      Functional connectivity assessed both by meta-analytic and resting fMRI
      approaches revealed that more anterior regions were more strongly connected to
      the default mode network, and more posterior regions were more strongly connected
      to 'task positive' regions. In addition, our analysis revealed that the anterior
      subregion was functionally connected to the ventral striatum, midbrain and
      amygdala, a circuit that is central to models of stress and motivated behavior.
      Analysis of a behavioral taxonomy provided evidence for a role for each subregion
      in mnemonic processing, as well as implication of the anterior subregion in
      emotional and visual processing and the right posterior subregion in reward
      processing. These findings lend support to models which posit anterior-posterior
      differentiation of function within the human hippocampal formation and complement
      other early steps toward a comparative (cross-species) model of the region.

PMID- 25776223
TI  - QM/MM studies reveal pathways leading to the quenching of the formation of
      thymine dimer photoproduct by flanking bases.
AB  - It is known that the formation of the photochemical product of thymine-thymine
      cyclobutane pyrimidine dimer (TT-CPD) formed upon UV excitation in DNA is
      significantly affected by the nature of the flanking bases, and that the
      oxidation potential of the flanking base correlates with the quenching of TT-CPD
      formation. However, the electronic details of this correlation have remained
      controversial. The quenching of thymine dimer formation exerted by flanking bases
      was suggested to be driven by both conformational and electronic effects. In the
      present study, we examine both of these effects using umbrella sampling and a
      quantum mechanical/molecular mechanical (QM/MM) approach for selected model
      systems. Our results demonstrate that a charge transfer (CT) state between the
      flanking base and the adjacent thymine base can provide a decay pathway for the
      population to escape from dimer formation, which eventually leads to the
      formation of an exciplex. The QM/MM vertical excitation energies also reveal that
      the oxidation potential of flanking bases correlates with the energy level of the
      CT state, thereby determining whether the CT state intersects with the state that
      can lead to dimer formation. The consistency between these results and
      experimentally obtained dimer formation rates implies that the quenching of dimer
      formation is mainly attributed to the decay pathway via the CT state. The present
      results further underline the importance of the electronic effects in quenching. 

PMID- 25776222
TI  - Recent Advances and the Future of Stem Cell Therapies in Amyotrophic Lateral
      Sclerosis.
AB  - Amyotrophic lateral sclerosis is a progressive neurodegenerative disease of the
      motor neurons without a known cure. Based on the possibility of cellular
      neuroprotection and early preclinical results, stem cells have gained widespread
      enthusiasm as a potential treatment strategy. Preclinical models demonstrate a
      protective role of engrafted stem cells and provided the basis for human trials
      carried out using various types of stem cells, as well as a range of cell
      delivery methods. To date, no trial has demonstrated a clear therapeutic benefit;
      however, results remain encouraging and are the basis for ongoing studies. In
      addition, stem cell technology continues to improve, and induced pluripotent stem
      cells may offer additional therapeutic options in the future. Improved disease
      models and clinical trials will be essential in order to validate stem cells as a
      beneficial therapy. 

PMID- 25776225
TI  - Feedback-giving behaviour in performance evaluations during clinical clerkships.
AB  - CONTEXT: Narrative feedback documented in performance evaluations by the teacher,
      i.e. the clinical supervisor, is generally accepted to be essential for workplace
      learning. Many studies have examined factors of influence on the usage of mini
      clinical evaluation exercise (mini-CEX) instruments and provision of feedback,
      but little is known about how these factors influence teachers' feedback-giving
      behaviour. In this study, we investigated teachers' use of mini-CEX in
      performance evaluations to provide narrative feedback in undergraduate clinical
      training. METHODS: We designed an exploratory qualitative study using an
      interpretive approach. Focusing on the usage of mini-CEX instruments in clinical
      training, we conducted semi-structured interviews to explore teachers'
      perceptions. Between February and June 2013, we conducted interviews with 14
      clinicians participated as teachers during undergraduate clinical clerkships.
      Informed by concepts from the literature, we coded interview transcripts and
      iteratively reduced and displayed data using template analysis. RESULTS: We
      identified three main themes of interrelated factors that influenced teachers'
      practice with regard to mini-CEX instruments: teacher-related factors; teacher
      student interaction-related factors, and teacher-context interaction-related
      factors. Four issues (direct observation, relationship between teacher and
      student, verbal versus written feedback, formative versus summative purposes)
      that are pertinent to workplace-based performance evaluations were presented to
      clarify how different factors interact with each other and influence teachers'
      feedback-giving behaviour. Embedding performance observation in clinical practice
      and establishing trustworthy teacher-student relationships in more longitudinal
      clinical clerkships were considered important in creating a learning environment
      that supports and facilitates the feedback exchange. CONCLUSION: Teachers'
      feedback-giving behaviour within the clinical context results from the
      interaction between personal, interpersonal and contextual factors. Increasing
      insight into how teachers use mini-CEX instruments in daily practice may offer
      strategies for creating a professional learning culture in which feedback giving
      and seeking would be enhanced.

PMID- 25776224
TI  - A standard photomap of ovarian nurse cell chromosomes in the European malaria
      vector Anopheles atroparvus.
AB  - Anopheles atroparvus (Diptera: Culicidae) is one of the main malaria vectors of
      the Maculipennis group in Europe. Cytogenetic analysis based on salivary gland
      chromosomes has been used in taxonomic and population genetic studies of
      mosquitoes from this group. However, a high-resolution cytogenetic map that could
      be used in physical genome mapping in An. atroparvus is still lacking. In the
      present study, a high-quality photomap of the polytene chromosomes from ovarian
      nurse cells of An. atroparvus was developed. Using fluorescent in situ
      hybridization, 10 genes from the five largest genomic supercontigs on the
      polytene chromosome were localized and 28% of the genome was anchored to the
      cytogenetic map. The study established chromosome arm homology between An.
      atroparvus and the major African malaria vector Anopheles gambiae, suggesting a
      whole-arm translocation between autosomes of these two species. The standard
      photomap constructed for ovarian nurse cell chromosomes of An. atroparvus will be
      useful for routine physical mapping. This map will assist in the development of a
      fine-scale chromosome-based genome assembly for this species and will also
      facilitate comparative and evolutionary genomics studies in the genus Anopheles. 

PMID- 25776226
TI  - Twelve tips for maximizing the effectiveness of game-based learning.
AB  - Game-based learning (GBL) in medical education is emerging as a valid alternative
      to traditional teaching methods. Well-designed GBL sessions use non-threatening
      competition to capitalize on heightened learner arousal, allowing for high-level
      engagement and dynamic group discussion. While many templates for specific
      educational games have been published, little has been written on strategies for
      educators to create their own or how to use them with maximal effectiveness.
      These 12 tips provide specific recommendations for the successful design and
      implementation of GBL sessions in medical education based on a review of the
      literature and insight from experienced designers. 

PMID- 25776227
TI  - Twelve Tips for teaching medical professionalism at all levels of medical
      education.
AB  - Review of studies published in medical education journals over the last decade
      reveals that teaching medical professionalism is essential, yet challenging.
      According to a recent Best Evidence in Medical Education (BEME) guide, there is
      no consensus on a theoretical or practical model to integrate the teaching of
      professionalism into medical education. The aim of this article is to outline a
      practical manual for teaching professionalism at all levels of medical education.
      Drawing from research literature and author's experience, Twelve Tips are listed
      and organised in four clusters with relevance to (1) the context, (2) the
      teachers, (3) the curriculum, and (4) the networking. With a better understanding
      of the guiding educational principles for teaching medical professionalism,
      medical educators will be able to teach one of the most challenging constructs in
      medical education. 

PMID- 25776228
TI  - The importance of educational theories for facilitating learning when using
      technology in medical education.
AB  - BACKGROUND: There is an increasing use of technology for teaching and learning in
      medical education but often the use of educational theory to inform the design is
      not made explicit. The educational theories, both normative and descriptive, used
      by medical educators determine how the technology is intended to facilitate
      learning and may explain why some interventions with technology may be less
      effective compared with others. AIMS: The aim of this study is to highlight the
      importance of medical educators making explicit the educational theories that
      inform their design of interventions using technology. METHOD: The use of
      illustrative examples of the main educational theories to demonstrate the
      importance of theories informing the design of interventions using technology.
      RESULTS: Highlights the use of educational theories for theory-based and
      realistic evaluations of the use of technology in medical education. CONCLUSION:
      An explicit description of the educational theories used to inform the design of
      an intervention with technology can provide potentially useful insights into why
      some interventions with technology are more effective than others. An explicit
      description is also an important aspect of the scholarship of using technology in
      medical education.

PMID- 25776229
TI  - An exploration of crossborder medical curriculum partnerships: Balancing
      curriculum equivalence and local adaptation.
AB  - CONTEXT: Worldwide, medical schools have entered into crossborder curriculum
      partnerships (CCPs) to provide equivalent curricula and learning experiences to
      groups of geographically separated students. Paradoxically, this process also
      involves adaptation of curricula to suit local contexts. This study has focused
      on challenges faced by medical Crossborder curriculum programme directors and
      strategies they employed to overcome these. METHODS: We conducted a qualitative
      study on six CCPs using document analysis and semi-structured interviews with 13
      programme directors from 12 medical schools. Interview transcripts were coded
      iteratively, followed by cross-case analysis. RESULTS: The challenges faced by
      CCP programme directors are four-fold, springing from differences in health care
      systems, legislation and political interference, teaching and learning
      environments, and partnership. Deliberate strategies, such as intensifying
      interactions between partners in all academic echelons, can help to overcome
      these. Partnerships vary in their setup and collaboration strategy. CONCLUSION:
      Medical CCPs are challenging though seem feasible. Partnerships with more solid
      integration of academic operations appear robust in terms of ownership and
      provide, besides financial, also academic advantages to both institutions.
      However, more research is needed on the long-term effects on quality of graduates
      and impact on the host health care system.

PMID- 25776231
TI  - Improved charge separation via Fe-doping of copper tungstate photoanodes.
AB  - Photoelectrochemical (PEC) water splitting offers a clean pathway to renewable
      and sustainable energy in the near future. The key to improving the efficiency of
      PEC devices is the ability to find materials with suitable optoelectronic
      properties, and identifying, then overcoming their limitations. In this paper, we
      explore the photoelectrochemical performance of CuWO4 photoanodes for solar water
      splitting, and find that charge separation is the dominant limitation for this
      material. As a result, we attempt to dope the material with Fe, the first such
      example of doping this semiconductor for PEC water splitting. An improvement in
      performance is achieved for doped films which show 1.5 times the photocurrent
      density and a 50% higher charge separation efficiency at 1.23 V vs. RHE. 

PMID- 25776230
TI  - Ehlers-Danlos syndrome type IV is associated with a novel G984R COL3A1 mutation.
AB  - Ehlers-Danlos syndrome type IV is an autosomal dominant connective tissue
      disease. Mutations in COL3A1 have been identified to underlie this disease;
      however, to the best of our knowledge, no COL3A1 mutations have been reported in
      Ehlers-Danlos syndrome type IV patients with an ascending aortic aneurysm. In
      order to develop further understanding of COL3A1 mutations, an Ehlers-Danlos
      syndrome type IV patient diagnosed with an ascending aortic aneurysm and a
      familial history of sudden mortality was analyzed. Genomic DNA was isolated from
      the peripheral blood of the patient and his family members. All coding exons of
      eight aneurysm-related genes (FBN1, TGFBR1, TGFBR 2, MYH11, ACTA2, SLC2A10,
      NOTCH1 and COL3A1) were amplified using polymerase chain reaction (PCR). The PCR
      products were sequenced with the ABI 3100 Genetic Analyzer, and a mutation was
      predicted and identified using Polyphen-2, SIFT and Mutation Taster. The novel
      mutation was identified as c.2950G>A in COL3A1, which results in p.G984R. All
      three programs predicted this mutation to be deleterous to the protein function.
      The novel mutation identified in this study is potentially responsible for Ehlers
      Danlos syndrome type IV in this patient, and expands the spectrum of COL3A1
      mutations.

PMID- 25776232
TI  - Publish and perish: how plagiarism can penalize perpetrators.

PMID- 25776233
TI  - Sentinel node biopsy in cutaneous melanoma: time for consensus to better inform
      patient choice.

PMID- 25776234
TI  - Chemical exposure in fetal/early life: a possible explanation for the rapid
      increase in atopic dermatitis incidence.

PMID- 25776235
TI  - Don't stop antithrombotics for cutaneous surgery: just do it now!

PMID- 25776236
TI  - A novel approach to port-wine stains.

PMID- 25776237
TI  - Pulsed dye laser treatment of superficial basal cell carcinoma.

PMID- 25776238
TI  - Some lasers are more equal than others.

PMID- 25776239
TI  - Thinner melanomas and improved survival among men in Sweden from 1997 to 2011.

PMID- 25776240
TI  - Head and neck melanoma: pattern of sun exposure and histological subtypes.

PMID- 25776241
TI  - Hypochromic vitiligo: a perspective.

PMID- 25776242
TI  - Recurrence rates in localized scleroderma (morphoea).

PMID- 25776243
TI  - Treatment of choice in superficial basal cell carcinoma.

PMID- 25776244
TI  - A new way of targeting phototherapy to body sites where it is needed.

PMID- 25776245
TI  - To (anti-)TNF or not (anti-)TNF? That is the question in pemphigus.

PMID- 25776246
TI  - No survival benefit for patients with melanoma undergoing sentinel lymph node
      biopsy: critical appraisal of the Multicenter Selective Lymphadenectomy Trial-I
      final report.
AB  - BACKGROUND: Sentinel lymph node biopsy (SLNB) was developed in the hope that it
      would improve outcomes for patients with melanoma. SLNB is an area of discussion
      and controversy in melanoma medicine. The final trial results of the Multicenter
      Selective Lymphadenectomy Trial (MSLT-I) have now been published and the authors
      suggest their long-term results 'clearly validate the use of sentinel-node biopsy
      in patients with intermediate-thickness or thick primary melanomas'. An
      accompanying editorial states that MSLT-I is a practice-changing trial.
      CONCLUSIONS: However, critical appraisal of MSLT-I data does not support the
      claims of the final report. On the contrary, MSLT-I failed to demonstrate that
      there is a significant treatment-related difference in the 10-year melanoma
      specific survival rate in the overall study population. Furthermore, there was no
      improvement in overall or melanoma-specific survival of the intermediate
      thickness group (1.2-3.5 mm). Completion lymphadenectomy can result in
      complications in about a third of patients, with a rate of clinically significant
      lymphoedema following axillary or groin dissection of 5-10%. Unnecessary
      lymphadenectomy can therefore have a major effect on patient quality of life. The
      evidence provided by Morton et al. does not support the claim that sentinel lymph
      node biopsy followed by lymphadenectomy in patients with positive sentinel nodes
      should be the standard of care in patients with melanoma. Readers are encouraged
      to check with registration sites to make sure declared primary outcomes are
      fairly reported. Post-hoc analyses are at best exploratory and cannot be used to
      form the principal conclusions of a trial.

PMID- 25776247
TI  - Multicenter Selective Lymphadenectomy Trial-I confirms the central role of
      sentinel node biopsy in contemporary melanoma management: response to 'No
      survival benefit for patients with melanoma undergoing sentinel lymph node
      biopsy: critical appraisal of the Multicenter Selective Lymphadenectomy Trial-I
      final report'.
AB  - Sentinel lymph node (SLN) biopsy has become a standard procedure for many
      patients with melanoma and is recommended in numerous national and professional
      melanoma guidelines. The Multicenter Selective Lymphadenectomy Trial (MSLT-1)
      confirms earlier large database studies and prospective clinical trials in
      demonstrating the independent and unequalled prognostic value of the SLN. It also
      demonstrates the ability of biopsy-directed management to provide effective
      regional disease control with the least possible morbidity. These benefits are
      not in question and provide ample justification for the procedure, even without
      evidence of a survival benefit. However, MSLT-1 also provides strong evidence of
      a substantial reduction in the risk of melanoma death for patients with
      intermediate thickness melanomas who harbour occult nodal metastases at the time
      of presentation. Denying appropriately selected patients with melanoma the
      opportunity to undergo SLN biopsy is no longer reasonable or acceptable. 

PMID- 25776251
TI  - A prospective, randomized, blinded, placebo-controlled pilot study on the effect
      of Enterococcus faecium on clinical activity and intestinal gene expression in
      canine food-responsive chronic enteropathy.
AB  - BACKGROUND: Canine chronic enteropathies (CE) are believed to be caused by an
      aberrant immune response towards the intestinal microbiome. Administration of
      probiotics can alleviate colitis in people. In vitro effects of the probiotic
      Enterococcus faecium NCIMB 10415 E1707 (EF) previously have been evaluated using
      canine cells (e.g., whole blood, intestinal biopsies), but data on in vivo
      efficacy are lacking. HYPOTHESIS/OBJECTIVES: Administration of EF to dogs with
      food-responsive CE will improve clinical outcome and decrease the intestinal
      inflammatory profile. ANIMALS: Dogs diagnosed with CE were prospectively
      recruited to receive a hydrolyzed elimination diet plus either a synbiotic
      product containing EF or placebo for 6 weeks. Both veterinary staff and owners
      were blinded to the treatment. METHODS: Clinical severity index (CCECAI),
      clinicopathological data and gene expression using intestinal biopsies
      (TLR2/4/5/9, IL-17A, IL-22, IL-23p19, RORC, IL-2, IL-12p35, TNFalpha, IL-4, IFNy,
      IL-10, TGFbeta, IL-1beta, IL-18, NLRP3, casp-1, TFF1, TFF3 and PPARy) before and
      after 6 weeks of treatment were analyzed using linear mixed modeling. RESULTS: Of
      the 45 cases recruited, 12 finished the clinical trial. Seven received the
      synbiotic and 5 the placebo product. There was no difference between groups or
      treatments regarding clinical efficacy, histology scores or expression of any of
      the investigated genes. CONCLUSIONS AND CLINICAL IMPORTANCE: Standard dietary
      treatment induced rapid clinical response in all cases. Because the study was
      underpowered, it was not possible to determine whether or not EF had an
      additional effect within the time period of 6 weeks.

PMID- 25776252
TI  - Unexpected behavioural consequences of preterm newborns' clothing.
AB  - Restrictions of preterm newborns' movements could have consequences ranging from
      stress enhancement to impairment of their motor development. Therefore, ability
      to freely express motor activities appears crucial for their behavioural and
      physiological development. Our aim was to evaluate behavioural issues of two
      types of clothing used in NICU. We observed 18 healthy 34-37 post-conception week
      old preterm newborns, during resting periods, when they were undisturbed by any
      interventions. Newborns wore either light clothing (bodysuit and a light
      wrapping) or heavy clothing (pyjamas, cardigan and sleep-sack). The percentages
      of time each subject spent in different postures were compared between clothing
      situations. Arm and hand postures differed in relation to clothing: babies bent
      their arms more and held their hands nearer their heads when in bodysuits than
      when in sleepwear. Consequently, babies in bodysuits spent more time touching
      their body or their environment whereas the others generally were touching
      nothing. Self-touch is an important way to comfort one's self. Heavy clothing may
      impair self-soothing behaviours of preterm newborn babies that already lack other
      forms of contact. Results suggest that more attention should be paid to
      apparently routine and marginal decisions such as choice of clothes. 

PMID- 25776253
TI  - First pinacol coupling in emulsified water: key role of surfactant and impact of
      alternative activation technologies.
AB  - For the first time, the influence of surfactants on the radical pinacol coupling
      reaction is investigated. The rate and selectivity of this reductive C-C coupling
      are compared under three different activation technologies: thermal activation,
      microwave irradiation, and sonication. The use of IgepalCO520, a neutral
      surfactant, led to the successful conversion of aromatic or alpha,beta
      unsaturated aliphatic carbonyl compounds in moderate to excellent yield (55-90
      %). An insight on the potential mechanism involved in the reaction is also
      proposed, based on microscopic observations and particle size measurement. 

PMID- 25776254
TI  - Letters to the editor.

PMID- 25776255
TI  - Unique Curing Properties through Living Polymerization in Crosslinking Materials:
      Polyurethane Photopolymers from Vinyl Ether Building Blocks.
AB  - Photopolymers with unique curing capabilities were produced by combining living
      cationic polymerization with network formation and restricted polymer motion. A
      vinyl ether diol was synthesized as a functional building block and reacted with
      isophorone diisocyanate to form a highly functionalized vinyl ether polyurethane
      as a model system with high crosslinking ability. When using a cationic
      photoinitiator, fast polymerization is observed upon short UV irradiation. Curing
      proceeds in the absence of light and under ambient conditions without oxygen
      inhibition. Cationic active sites become trapped dormant species upon network
      induced vitrification and surprisingly remain living for several days. The
      polymerization can be reactivated by additional UV irradiation and/or raised
      temperature. The curing behavior was studied in detail by using UV and FT-NIR
      coupled rheology and photo-DSC to simultaneously study spectroscopic and
      mechanical information, as well as thermal effects. 

PMID- 25776256
TI  - Information needs among patients and a surveillance strategy after surgery for
      pancreatic and periampullary cancer.

PMID- 25776259
TI  - Viral infection: Tracking down HIV's hiding place.

PMID- 25776264
TI  - Antifungal nanofibers made by controlled release of sea animal derived peptide.
AB  - Candida albicans is a common human-pathogenic fungal species with the ability to
      cause several diseases including surface infections. Despite the clear
      difficulties of Candida control, antimicrobial peptides (AMPs) have emerged as an
      alternative strategy for fungal control. In this report, different concentrations
      of antifungal Cm-p1 (Cencritchis muricatus peptide 1) were electrospun into
      nanofibers for drug delivery. The nanofibers were characterized by mass
      spectrometry confirming the presence of the peptide on the scaffold. Atomic force
      microscopy and scanning electronic microscopy were used to measure the diameters,
      showing that Cm-p1 affects fiber morphology as well as the diameter and scaffold
      thickness. The Cm-p1 release behavior from the nanofibers demonstrated peptide
      release from 30 min to three days, leading to effective yeast control in the
      first 24 hours. Moreover, the biocompatibility of the fibers were evaluated
      through a MTS assay as well as ROS production by using a HUVEC model, showing
      that the fibers do not affect cell viability and only nanofibers containing 10%
      Cm-p1-PVA improved ROS generation. In addition, the secretion of pro-inflammatory
      cytokines IL-6 and TNF-alpha by the HUVECs was also slightly modified by the 10%
      Cm-p1-PVA nanofibers. In conclusion, the electrospinning technique applied here
      allowed for the manufacture of biodegradable biomimetic nanofibrous extracellular
      membranes with the ability to control fungal infection. 

PMID- 25776266
TI  - Vestibular dysfunction in patients with post-mumps sensorineural hearing loss.
AB  - OBJECTIVE: To study the possible damage to the vestibular system in patients with
      post-mumps sensorineural hearing loss. METHODS: Nineteen patients with recent
      mumps infection participated in the study. All patients had unilateral profound
      sensorineural hearing loss or total hearing loss. Patients were subjected to
      video-nystagmography and vestibular-evoked myogenic potential testing. RESULTS:
      Eight patients (42.1 per cent) had normal video-nystagmography results and intact
      vestibular-evoked myogenic potentials on both sides, whereas the other 11
      patients (57.9 per cent) had vestibular lesions in the form of marked canal
      weakness and absent vestibular-evoked myogenic potential responses on the same
      side as hearing loss. The overall findings indicated a peripheral site for the
      lesions. CONCLUSION: The majority of patients with post-mumps sensorineural
      hearing loss had peripheral vestibular pathology in the same ear as hearing loss.
      Further research should be directed to saving the inner ear following mumps
      infection.

PMID- 25776265
TI  - The glycan role in the glycopeptide immunogenicity revealed by atomistic
      simulations and spectroscopic experiments on the multiple sclerosis biomarker
      CSF114(Glc).
AB  - Glycoproteins are often recognized as not-self molecules by antibodies triggering
      the onset of severe autoimmune diseases such as Multiple Sclerosis (MS). Thus,
      the development of antigen-mimicking biomarkers represents an attractive strategy
      for an early diagnosis of the disease. An example is the synthetic glycopeptide
      CSF114(Glc), which was designed and tested as MS biomarker and whose clinical
      application was limited by its reduced ability to detect autoantibodies in MS
      patients. In the attempt to improve the efficacy of CSF114(Glc), we have
      characterized all the events leading to the final binding of the biomarker to the
      autoantibody using atomistic simulations, ESR and NMR experiments. The glycosydic
      moiety plays a primary role in the whole process. In particular, in an
      environment mimicking that used in the clinical tests the glycopeptide assumes a
      alpha-helix structure that is functional for the interaction with the antibody.
      In this conformation CSF114(Glc) binds the monoclonal antibody mAb8-18C5
      similarly to the myelin oligodendrocyte glycoprotein MOG, which is a known MS
      auto-antigen, thus explaining its diagnostic activity. Our study offers new
      molecular bases to design more effective biomarkers and provides a most valid
      protocol to investigate other systems where the environment effect is determinant
      for the biological activity. 

PMID- 25776267
TI  - Interleukin-1 Acts via the JNK-2 Signaling Pathway to Induce Aggrecan Degradation
      by Human Chondrocytes.
AB  - OBJECTIVE: Aggrecan enables articular cartilage to bear load and resist
      compression. Aggrecan loss occurs early in osteoarthritis and rheumatoid
      arthritis and can be induced by inflammatory cytokines such as interleukin-1 (IL
      1). IL-1 induces cleavage of specific aggrecans characteristic of the ADAMTS
      proteinases. The aim of this study was to identify the intracellular signaling
      pathways by which IL-1 causes aggrecan degradation by human chondrocytes and to
      investigate how aggrecanase activity is controlled by chondrocytes. METHODS: We
      developed a cell-based assay combining small interfering RNA (siRNA)-induced
      knockdown with aggrecan degradation assays. Human articular chondrocytes were
      overlaid with bovine aggrecan after transfection with siRNAs against molecules of
      the IL-1 signaling pathway. After IL-1 stimulation, released aggrecan fragments
      were detected with AGEG and ARGS neoepitope antibodies. Aggrecanase activity and
      tissue inhibitor of metalloproteinases 3 levels were measured by enzyme-linked
      immunosorbent assay. Low-density lipoprotein receptor-related protein 1 (LRP-1)
      shedding was analyzed by Western blotting. RESULTS: ADAMTS-5 is a major
      aggrecanase in human chondrocytes, regulating aggrecan degradation in response to
      IL-1. The tumor necrosis factor receptor-associated 6 (TRAF-6)/transforming
      growth factor beta-activated kinase 1 (TAK-1)/MKK-4 signaling axis is essential
      for IL-1-induced aggrecan degradation, while NF-kappaB is not. Of the 3 MAPKs
      (ERK, p38, and JNK), only JNK-2 showed a significant role in aggrecan
      degradation. Chondrocytes constitutively secreted aggrecanase, which was
      continuously endocytosed by LRP-1, keeping the extracellular level of aggrecanase
      low. IL-1 induced aggrecanase activity in the medium in a JNK-2-dependent manner,
      possibly by reducing aggrecanase endocytosis, because IL-1 caused JNK-2-dependent
      shedding of LRP-1. CONCLUSION: The signaling axis TRAF-6/TAK-1/MKK-4/JNK-2
      mediates IL-1-induced aggrecanolysis. The level of aggrecanase is controlled by
      its endocytosis, which may be reduced upon IL-1 stimulation because of LRP-1
      shedding.

PMID- 25776270
TI  - Isolation of plant-growth-promoting rhizobacteria from rhizospheric soil of
      halophytes and their impact on maize (Zea mays L.) under induced soil salinity.
AB  - The present investigation was aimed to scrutinize the salt tolerance potential of
      plant-growth-promoting rhizobacteria (PGPR) isolated from rhizospheric soil of
      selected halophytes (Atriplex leucoclada, Haloxylon salicornicum, Lespedeza
      bicolor, Suaeda fruticosa, and Salicornica virginica) collected from high-saline
      fields (electrical conductivity 4.3-5.5) of District Mardan, Pakistan. Five PGPR
      strains were identified using 16S rRNA amplification and sequence analysis.
      Bacillus sp., isolated from rhizospheric soil of Atriplex leucoclada, and
      Arthrobacter pascens, isolated from rhizospheric soil of Suaeda fruticosa, are
      active phosphate solubilizers and bacteriocin and siderophore producers; hence,
      their inoculation and co-inoculation on maize ('Rakaposhi') under induced
      salinity stress enhanced shoot and root length and shoot and root fresh and dry
      mass. The accumulation of osmolytes, including sugar and proline, and the
      elevation of antioxidant enzymes activity, including superoxide dismutase,
      peroxidase, catalase, and ascorbate peroxidase, were enhanced in the maize
      variety when inoculated and co-inoculated with Bacillus sp. and Arthrobacter
      pascens. The PGPR (Bacillus sp. and A. pascens) isolated from the rhizosphere of
      the mentioned halophytes species showed reliability in growth promotion of maize
      crop in all the physiological parameters; hence, they can be used as bio
      inoculants for the plants growing under salt stress. 

PMID- 25776271
TI  - Parental Age and Autism Spectrum Disorders Among New York City Children 0-36
      Months of Age.
AB  - We examined trends in autism spectrum disorders (ASD) and the association of ASD
      with parental age among young New York City (NYC) children. Children born in NYC
      to resident mothers from 1994-2001 were identified through vital statistics
      records (N = 927,003). Records were linked to data from NYC Early Intervention
      (EI) Program through 2004. The independent parental age-specific odds of having
      an ASD before 36 months of age were estimated using multiple logistic regression
      controlling for risk factors. The increase in ASD attributable to changes in
      parental age at birth was examined. Births to mothers and fathers 35 years or
      older increased 14.9 and 11.5 %, respectively, between 1994 and 2001. ASD
      prevalence in EI increased significantly from 1 in 3,300 children born in 1994 to
      1 in 233 children born in 2001. Children born to mothers ages 25-29, 30-34 and 35
      or older had significantly greater odds of being diagnosed with ASD than children
      of mothers younger than 25 years (OR 1.5, 1.6, and 1.9, respectively). Children
      born to fathers ages 35 or older (OR 1.4) had greater odds of ASD than children
      of fathers younger than 25. The change in parental age accounted for only 2.7 %
      of the increase in ASD prevalence. Older paternal age and maternal age were
      independently associated with increased risk of ASD. However, while parental age
      at birth increased between the 1994 and 2001 birth cohorts in NYC, it did not
      explain the increase in number of ASD cases.

PMID- 25776272
TI  - miR-338-3p suppresses tumor growth of ovarian epithelial carcinoma by targeting
      Runx2.
AB  - miR-338-3p, a recently discovered miRNA, has been shown to play important roles
      in tumorigenesis and metastasis in various cancers. However, the exact roles and
      mechanisms of miR-338-3p remain unknown in human ovarian epithelial carcinoma
      (EOC). The relationship between miR-338-3p expression pattern and
      clinicopathological features of patients with EOC were determined by real-time
      quantitative RT-PCR. Furthermore, the role of miR-338-3p and possible molecular
      mechanisms in EOC was investigated by several in vitro approaches and in a nude
      mouse model. We first showed that the expression of miR-338-3p was significantly
      downregulated in EOC tissues compared to those in adjacent normal tissues, and
      the value was negatively related to advanced FIGO stage, high histological
      grading and lymph node metastasis (P<0.01). An in vitro analysis revealed that
      the overexpression of miR-338-3p in EOC cells significantly inhibited cell
      proliferation, colony formation, migration and invasion, inducing cell apoptosis
      and enhancing caspase-3, -8, and -9 activities. Bioinformatic analysis and dual
      luciferase assays identified Runx2 as a direct target of miR-338-3p. We also
      found that enforced expression of miR-338-3p markedly inhibited the in vivo
      tumorigenicity in a nude mouse xenograft model system. Furthermore,
      overexpression of miR-338-3p inhibited phosphorylation of PI3K and AKT, which
      contributed to suppression of ovarian cancer cell growth. These findings revealed
      that miR-338-3p may act as a tumor suppressor that blocks the growth of human
      ovarian epithelial carcinoma through PI3K/AKT signaling pathways by targeting
      Runx2.

PMID- 25776273
TI  - The neuropsychology of obsessive-compulsive personality disorder: a new analysis.
AB  - BACKGROUND: Obsessive compulsive personality disorder (OCPD) is characterized by
      perfectionism, need for control, and cognitive rigidity. Currently, little
      neuropsychological data exist on this condition, though emerging evidence does
      suggest that disorders marked by compulsivity, including obsessive-compulsive
      disorder (OCD), are associated with impairment in cognitive flexibility and
      executive planning on neurocognitive tasks. AIM: The current study investigated
      the neurocognitive profile in a nonclinical community-based sample of people
      fulfilling diagnostic criteria for OCPD in the absence of major psychiatric
      comorbidity. METHOD: Twenty-one nonclinical subjects who fulfilled Diagnostic and
      Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) criteria for OCPD
      were compared with 15 healthy controls on selected clinical and neurocognitive
      tasks. OCPD was measured using the Compulsive Personality Assessment Scale
      (CPAS). Participants completed tests from the Cambridge Automated
      Neuropsychological Test Battery including tests of set shifting (Intra-Extra
      Dimensional [IED] Set Shifting) executive planning (Stockings of Cambridge
      [SOC]), and decision making (Cambridge Gamble Task [CGT]). RESULTS: The OCPD
      group made significantly more IED-ED shift errors and total shift errors, and
      also showed longer mean initial thinking time on the SOC at moderate levels of
      difficulty. No differences emerged on the CGT. CONCLUSIONS: Nonclinical cases of
      OCPD showed significant cognitive inflexibility coupled with executive planning
      deficits, whereas decision-making remained intact. This profile of impairment
      overlaps with that of OCD and implies that common neuropsychological changes
      affect individuals with these disorders.

PMID- 25776274
TI  - Multisegmented FeCo/Cu nanowires: electrosynthesis, characterization, and
      magnetic control of biomolecule desorption.
AB  - In this paper, we report on the synthesis of FeCo/Cu multisegmented nanowires by
      means of pulse electrodeposition in nanoporous anodic aluminum oxide arrays
      supported on silicon chips. By adjustment of the electrodeposition conditions,
      such as the pulse scheme and the electrolyte, alternating segments of Cu and
      ferromagnetic FeCo alloy can be fabricated. The segments can be built with a wide
      range of lengths (15-150 nm) and exhibit a close-to-pure composition (Cu or FeCo
      alloy) as suggested by energy-dispersive X-ray mapping results. The morphology
      and the crystallographic structure of different nanowire configurations have been
      assessed thoroughly, concluding that Fe, Co, and Cu form solid solution. Magnetic
      characterization using vibrating sample magnetometry and magnetic force
      microscopy reveals that by introduction of nonmagnetic Cu segments within the
      nanowire architecture, the magnetic easy axis can be modified and the reduced
      remanence can be tuned to the desired values. The experimental results are in
      agreement with the provided simulations. Furthermore, the influence of nanowire
      magnetic architecture on the magnetically triggered protein desorption is
      evaluated for three types of nanowires: Cu, FeCo, and multisegmented
      FeCo15nm/Cu15nm. The application of an external magnetic field can be used to
      enhance the release of proteins on demand. For fully magnetic FeCo nanowires the
      applied oscillating field increased protein release by 83%, whereas this was
      found to be 45% for multisegmented FeCo15nm/Cu15nm nanowires. Our work suggests
      that a combination of arrays of nanowires with different magnetic configurations
      could be used to generate complex substance concentration gradients or control
      delivery of multiple drugs and macromolecules. 

PMID- 25776275
TI  - Diversity of regulatory mechanisms of photosynthetic carbon metabolism in plants
      and algae.
AB  - To clarify the regulatory mechanisms of the Calvin cycle in algae, we analyzed
      the molecular properties of the enzymes involved in this cycle. We demonstrated
      that these enzymes were not regulated by redox modulation through the
      ferredoxin/thioredoxin system under light/dark conditions and were not sensitive
      to treatments with hydrogen peroxide in vitro, unlike the chloroplastic thiol
      modulated enzymes of plants. On the other hand, we found that cyanobacteria
      possessed a unique enzyme involved in the Calvin cycle. The CP12 protein played
      an important role in regulating carbon metabolism in the Calvin cycle in
      cyanobacteria and eukaryotic algae. This review described the regulatory
      mechanisms of the Calvin cycle in algae and also the effects of alterations to
      photosynthetic carbon metabolism on plant productivity, carbon partitioning, and
      the carbon/nitrogen balance using transgenic plants expressing algal genes. 

PMID- 25776276
TI  - Severe chronic insomnia is not associated with higher body mass index.
AB  - Short sleep duration is widely considered to be a risk factor for weight gain,
      suggesting that patients suffering from sleep disorders are a risk group. Despite
      some positive preliminary data on patients with organic sleep disorders,
      empirical evidence for an increased body mass index in patients with insomnia is
      scarce. Two-hundred and thirty-three patients with a confirmed diagnosis of
      severe and chronic insomnia without co-morbidity showing objectively impaired
      sleep quality were compared with respect to their body mass index with control
      data derived from a representative population survey matched in gender and age.
      As a result, patients with insomnia showed a lower body mass index (23.8 kg m(-2)
      versus 27.1 kg m(-2) ; P < 0.0005). Our findings suggest that patients with
      chronic insomnia do not exhibit overweight. These data are a valuable educational
      tool to calm patients' fears about the consequences of insomnia, and contribute
      to the understanding of chronically disturbed sleep and weight regulation. 

PMID- 25776278
TI  - In vitro inhibition and induction of human cytochrome P450 enzymes by SIPI5357, a
      potential antidepressant.
AB  - This study investigated the in vitro drug-drug interaction potential of SIPI5357,
      an arylalkanol-piperazine derivative used in the treatment of depression. Drug
      drug interaction occurs via inhibition or induction of enzymes involved in their
      metabolism. In human liver microsomes, SIPI5357 showed the strongest inhibition
      of CYP2D6, followed by CYP3A4 (testosterone) and CYP2C8. Inhibition was observed
      in a concentration-dependent manner, with IC50 values of 18.45 uM, 36.63 uM
      (CYP3A4/testosterone), 89.23 uM, respectively. SIPI5357 was predicted not to
      cause significant metabolic drug-drug interaction via inhibition of CYP1A2,
      CYP2C9, CYP2C19, CYP2E1 or CYP3A4 (midazolam) because the IC50 values for these
      enzymes were both >100 uM (200 times maximum plasma concentration [Cmax ]).
      SIPI5357 showed a mixed model inhibition of CYP2D6 (Ki = 11.12 uM). The value of
      [I]/Ki for CYP2D6 inhibition by SIPI5357 is below the FDA cut-off value of 0.1;
      it is therefore reasonable to assume that SIPI5357 will not cause significant
      CYP2D6 inhibition. However, positive controls (50 uM omeprazole and 25 uM
      rifampin) caused the anticipated CYP induction, but the highest concentration of
      SIPI5357 (5 uM; 10 times plasma Cmax ) had a minimal effect on CYP1A2 and CYP3A4
      mRNA levels in freshly isolated human hepatocytes, suggesting that SIPI5357 is
      not an inducer of these enzymes. However, significant induction of CYP2B6 was
      observed at 0.5 uM and 5 uM. In conclusion, SIPI5357 might cause drug-drug
      interaction via induction of CYP2B6. The in vivo drug-drug interaction potential
      deserves further investigation. Copyright (c) 2015 John Wiley & Sons, Ltd.

PMID- 25776277
TI  - High-density genetic map construction and identification of a locus controlling
      weeping trait in an ornamental woody plant (Prunus mume Sieb. et Zucc).
AB  - High-density genetic map is a valuable tool for fine mapping locus controlling a
      specific trait especially for perennial woody plants. In this study, we firstly
      constructed a high-density genetic map of mei (Prunus mume) using SLAF markers,
      developed by specific locus amplified fragment sequencing (SLAF-seq). The linkage
      map contains 8,007 markers, with a mean marker distance of 0.195 cM, making it
      the densest genetic map for the genus Prunus. Though weeping trees are used
      worldwide as landscape plants, little is known about weeping controlling gene(s)
      (Pl). To test the utility of the high-density genetic map, we did fine-scale
      mapping of this important ornamental trait. In total, three statistic methods
      were performed progressively based on the result of inheritance analysis.
      Quantitative trait loci (QTL) analysis initially revealed that a locus on linkage
      group 7 was strongly responsible for weeping trait. Mutmap-like strategy and
      extreme linkage analysis were then applied to fine map this locus within 1.14 cM.
      Bioinformatics analysis of the locus identified some candidate genes. The
      successful localization of weeping trait strongly indicates that the high-density
      map constructed using SLAF markers is a worthy reference for mapping important
      traits for woody plants. 

PMID- 25776279
TI  - Oral Secondary Syphilis.
AB  - Secondary syphilis develops in approximately 25% of patients infected with the
      spirochete bacterium Treponema pallidum. It typically develops several weeks to
      several months after the primary infection, which is recognized by a painless
      chancre. Secondary syphilis is characterized by systemic symptoms, such as
      malaise and fever as well as a maculopapular rash involving the trunk and
      extremities including the palms and soles. Condyloma lata, which are raised,
      fleshy lesions, tend to develop at the site of the primary chancre. Diagnosis is
      achieved primarily through screening and confirmational serologic testing.
      Histologic findings seen in condyloma lata are largely non-specific. Therefore, a
      high index of suspicion should be maintained and immunohistochemical stains
      specific for T. pallidum should be utilized.

PMID- 25776280
TI  - Designed hybrid nanostructure with catalytic effect: beyond the theoretical
      capacity of SnO2 anode material for lithium ion batteries.
AB  - Transition metal cobalt (Co) nanoparticle was designed as catalyst to promote the
      conversion reaction of Sn to SnO2 during the delithiation process which is deemed
      as an irreversible reaction. The designed nanocomposite, named as
      SnO2/Co3O4/reduced-graphene-oxide (rGO), was synthesized by a simple two-step
      method composed of hydrothermal (1(st) step) and solvothermal (2(nd) step)
      synthesis processes. Compared to the pristine SnO2/rGO and SnO2/Co3O4 electrodes,
      SnO2/Co3O4/rGO nanocomposites exhibit significantly enhanced electrochemical
      performance as the anode material of lithium-ion batteries (LIBs). The
      SnO2/Co3O4/rGO nanocomposites can deliver high specific capacities of 1038 and
      712 mAh g(-1) at the current densities of 100 and 1000 mA g(-1), respectively. In
      addition, the SnO2/Co3O4/rGO nanocomposites also exhibit 641 mAh g(-1) at a high
      current density of 1000 mA g(-1) after 900 cycles, indicating an ultra-long
      cycling stability under high current density. Through ex-situ TEM analysis, the
      excellent electrochemical performance was attributed to the catalytic effect of
      Co nanoparticles to promote the conversion of Sn to SnO2 and the decomposition of
      Li2O during the delithiation process. Based on the results, herein we propose a
      new method in employing the catalyst to increase the capacity of alloying
      dealloying type anode material to beyond its theoretical value and enhance the
      electrochemical performance.

PMID- 25776281
TI  - Contraception in the postpartum period: immediate options for long-acting
      success.

PMID- 25776282
TI  - Optimal staging of lymphoma during pregnancy is crucial.

PMID- 25776283
TI  - Author response: Precise staging of lymphoma duringpregnancy using MRI is not
      always crucial.

PMID- 25776284
TI  - Improving the care pathway for women with incontinence.

PMID- 25776285
TI  - Adapting an evidence-based survivorship intervention for Latina breast cancer
      survivors.
AB  - AIM: About 120,000 Latina breast cancer survivors (LBCS) live in the USA with the
      numbers expected to increase. LBCS experience survivorship disparities and report
      poor quality of life outcomes. Despite poor outcomes, few survivorship
      interventions for LBCS are available. Adapting evidence-based interventions for
      Latinas may be one strategy to reduce disparities. MATERIALS & METHODS: An
      evidence-based intervention called the Breast Cancer Education Intervention was
      adapted for Latinas. First, certified translation and cognitive interview to
      assess cultural relevance were conducted. Next, a pilot sample of 40 Latinas who
      participated in the intervention were asked to provide follow-up evaluation of
      their satisfaction with and usefulness of the translated education manual and
      intervention. RESULTS: Thirty LBCS completed the intervention, and 14 LBCS
      submitted an evaluation summary expressing satisfaction with usefulness,
      readability and relevance. CONCLUSION: The process by which translation and
      cultural adaptation of an evidence-based intervention provides beginning
      foundation to support and reduce disparities among LBCS.

PMID- 25776286
TI  - Asymptomatic cervical polyps: can we just let them be?
AB  - AIM: Routine polypectomy is still practiced in many settings. The objective of
      this study was to establish the frequency of dysplasia or malignancy found in
      cervical polyps from a multiyear sample after abnormal specimens performed for
      indication were excluded. MATERIALS & METHODS: This is a retrospective study of
      the pathology results from 2006-2013, inclusive. RESULTS: The study included 898
      polyps from 854 nonpregnant women, after the 17 abnormal specimens from women who
      presented with complaints of abnormal bleeding or for evaluation of abnormal
      cytological tests were excluded; none of the 898 specimens showed any significant
      abnormalities. The results did not vary by patient age or polyp size. CONCLUSION:
      Routine removal of cervical polyps in asymptomatic women with current, normal
      cervical cytology testing is unwarranted because it adds little to their
      management and it has the potential to cause harm.

PMID- 25776287
TI  - Exploring the relationship between endometriomas and infertility.
AB  - Several clinical and epidemiological studies demonstrated an association between
      endometriosis and infertility. A role in the genesis of infertility may be played
      by endometriomas, which may interfere with ovulation or damage ovarian tissue.
      Unlike peritoneal implants, the availability of an accurate noninvasive
      sonographic diagnosis facilitates the investigation of endometrioma associated
      infertility. The laparoscopic excision of an endometrioma relieves the ovary from
      the damage caused by the cyst itself, which may be progressive over time, but at
      the same time is associated with a detrimental effect on ovarian reserve and with
      high rates of postoperative endometrioma recurrence. Therefore, the management of
      endometrioma-related infertility should not be based upon surgery alone, but upon
      a combination of surgery, with a refinement of the operating technique, long-term
      oral contraceptive, in vitro fertilization and oocyte cryopreservation. 

PMID- 25776288
TI  - Polycystic ovary syndrome and insulin: our understanding in the past, present and
      future.
AB  - Insulin resistance is prevalent in women with polycystic ovary syndrome (PCOS),
      and plays a critical pathophysiologic role in both the metabolic and reproductive
      complications of PCOS. This review focuses on the contribution of insulin
      resistance to anovulation in PCOS and to the high risk for Type 2 diabetes,
      metabolic syndrome and early cardiovasular disease. Key points for clinicians
      emphasized by this review are the following: PCOS is a clinical diagnosis and
      alternative diagnoses must be excluded; PCOS carries an inherent risk of insulin
      resistance and, hence, metabolic consequences for which women with PCOS should be
      screened regardless of BMI or degree of obesity; and PCOS is associated with
      infertility and this should be discussed early on in care of women diagnosed with
      PCOS, recognizing that there are several possible strategies to address
      infertility in women with PCOS, each with its own risks and benefits. 

PMID- 25776289
TI  - Should we abandon all conservative treatments for uterine fibroids? The problem
      with leiomyosarcomas.
AB  - Fibroids are the most common tumor in women and many medical and surgical options
      exist for their management. The incidence of uterine sarcoma in women undergoing
      treatment for fibroids has previously been thought to be extremely rare, however
      there has been recent controversy as to whether this risk has been
      underestimated. This article reviews the literature investigating the incidence
      of leiomyosarcoma and explores how different treatment modalities may affect risk
      from occult malignancy. We aim to provide a tool for counseling women who are
      considering options for the management of their fibroids. 

PMID- 25776290
TI  - Minimally invasive surgical options for congenital and acquired uterine factors
      associated with recurrent pregnancy loss.
AB  - Recurrent pregnancy loss (RPL) is defined as two or more failed clinical
      pregnancies before 20 weeks' gestation and may be caused by genetic,
      endocrinologic, anatomic and immunologic abnormalities. Anatomic uterine
      anomalies include congenital malformations (bicornuate, didelphic, septate and
      unicornuate uteri) and acquired defects (fibroids, adenomas, adhesions and
      polyps). Women with septate and bicornuate uteri, intrauterine adhesions, and
      some adenomas and fibroids are at increased risk of RPL. Data support surgical
      treatment of all of these lesions except bicornuate uteri. The role of polyps in
      RPL is unclear. Minimally invasive options for surgical correction of
      intrauterine lesions include hysteroscopy, laparoscopy with and without robotic
      assistance and minilaparotomy. 

PMID- 25776291
TI  - Current concepts in premature ovarian insufficiency.
AB  - Premature ovarian insufficiency (POI) is a life-changing diagnosis, with profound
      physical and psychological consequences. Unfortunately, there are many
      deficiencies in our understanding of the condition as the underlying etiology and
      optimum management strategies are poorly understood. Improved awareness of POI
      and its long-term implications has led to increased research interest in recent
      years. Current research has allowed a greater understanding of the changing
      epidemiology in POI, genetic factors in its etiology and randomized controlled
      trials of hormone therapy are underway to provide evidence for treatment. This
      article reviews the latest literature on POI to summarize current understanding
      and future directions. 

PMID- 25776292
TI  - Maternal complications and the management of asthma in pregnancy.
AB  - Pregnancy is a unique state requiring alterations in maternal physiology to
      accommodate the growing fetus. Whilst the maternal immune system is normally well
      adept at performing this task, the presence of immune disorders, such as asthma,
      often lead to pregnancy-related complications affecting both mother and baby.
      Australia has a high prevalence of asthma; with approximately 12% of pregnant
      women reported to have current asthma. Poor control of asthma is of far greater
      risk than the use of asthma medications. Being able to identify complications
      associated with asthma during pregnancy is of great importance in providing
      appropriate asthma management and medical care to these pregnant women, which may
      have lifelong consequences for their offspring. 

PMID- 25776293
TI  - Next steps to reduce maternal morbidity and mortality in the USA.
AB  - Maternal mortality is rising in the USA. The pregnancy-related maternal mortality
      ratio increased from 10/100,000 to 17/100,000 live births from the 1990s to 2012.
      A large proportion of maternal deaths are preventable. This review highlights a
      national approach to reduce maternal death and morbidity and discusses multiple
      efforts to reduce maternal morbidity, death and improve obstetric safety. These
      efforts include communication and collaboration between all stake holders
      involved in perinatal health, creation of national bundles addressing key
      maternal care areas such as hemorrhage management, call for all obstetric
      hospitals to review and analyze all cases of severe maternal morbidity, and
      access to contraception. Implementation of interventions based on these efforts
      is a national imperative to improve obstetric safety. 

PMID- 25776294
TI  - The next steps in cervical screening.
AB  - Cervical cancer is fourth most common cancer among women with four-fifths of the
      global burden in low- and middle-income countries (LMICs). Persistent infection
      with one of the high-risk types of human papillomaviruses (HPV), particularly HPV
      16/18, is the central cause of cervical neoplasia. Progress in developing
      feasible, alternative screening methods in LMICs and HPV vaccines have further
      improved cervical cancer prevention prospects. While existing screening programs
      in high-income countries should be re-organized, in view of the downstream
      effects of national HPV vaccination programs, LMICs should introduce national
      programs to vaccinate single year cohorts of girls aged 9-13 years with two or
      three doses and screen 30-35-year-old women with HPV testing to pragmatically
      decrease their high disease burden. 

PMID- 25776295
TI  - Personalized assessment and management of women at risk for breast cancer in
      North America.
AB  - Many women at increased risk for breast cancer would benefit from referral for
      genetic testing, enhanced screening, preventive therapy or risk-reducing surgery.
      We present a visual model and a step-wise approach to assist with a personalized
      risk stratification and management of these women. We present current
      recommendations with respect to lifestyle behaviors and mammographic screening,
      and we review the current evidence regarding enhanced screening and risk-reducing
      therapies. We discuss the usefulness of three risk-assessment tools in
      determining whether a woman qualifies for genetic testing, enhanced screening or
      preventive therapy and present four cases to demonstrate the usefulness of this
      approach in the clinical setting. 

PMID- 25776296
TI  - Impact of fecal incontinence and its treatment on quality of life in women.
AB  - Fecal incontinence (FI) is a physically and psychosocially debilitating disorder
      which negatively impacts quality of life (QOL). It bears a significant burden not
      only on patients but also on their families, caretakers as well as society as a
      whole. Even though it is considered a somewhat common condition, especially as
      women age, the prevalence is often underestimated due to patients' reluctance to
      report symptoms or seek care. The evaluation and treatment of FI can be also
      hindered by lack of understanding of the current management options among
      healthcare providers and how they impact on QOL. This article provides a
      comprehensive review on the impact of FI and its treatment on QOL in women. 

PMID- 25776301
TI  - Mutant prevention concentration, pharmacokinetic-pharmacodynamic integration, and
      modeling of enrofloxacin data established in diseased buffalo calves.
AB  - The pharmacokinetic-pharmacodynamic (PK/PD) modeling of enrofloxacin data using
      mutant prevention concentration (MPC) of enrofloxacin was conducted in febrile
      buffalo calves to optimize dosage regimen and to prevent the emergence of
      antimicrobial resistance. The serum peak concentration (Cmax ), terminal half
      life (t1/2 K10) , apparent volume of distribution (Vd(area) /F), and mean
      residence time (MRT) of enrofloxacin were 1.40 +/- 0.27 MUg/mL, 7.96 +/- 0.86 h,
      7.74 +/- 1.26 L/kg, and 11.57 +/- 1.01 h, respectively, following drug
      administration at dosage 12 mg/kg by intramuscular route. The minimum inhibitory
      concentration (MIC), minimum bactericidal concentration, and MPC of enrofloxacin
      against Pasteurella multocida were 0.055, 0.060, and 1.45 MUg/mL, respectively.
      Modeling of ex vivo growth inhibition data to the sigmoid Emax equation provided
      AUC24 h /MIC values to produce effects of bacteriostatic (33 h), bactericidal (39
      h), and bacterial eradication (41 h). The estimated daily dosage of enrofloxacin
      in febrile buffalo calves was 3.5 and 8.4 mg/kg against P. multocida/pathogens
      having MIC90 <=0.125 and 0.30 MUg/mL, respectively, based on the determined AUC24
      h /MIC values by modeling PK/PD data. The lipopolysaccharide-induced fever had no
      direct effect on the antibacterial activity of the enrofloxacin and alterations
      in PK of the drug, and its metabolite will be beneficial for its use to treat
      infectious diseases caused by sensitive pathogens in buffalo species. In
      addition, in vitro MPC data in conjunction with in vivo PK data indicated that
      clinically it would be easier to eradicate less susceptible strains of P.
      multocida in diseased calves. 

PMID- 25776302
TI  - Routine conventional karyotyping of lymphoma staging bone marrow samples does not
      contribute clinically relevant information.
AB  - Bone marrow (BM) evaluation is an important part of lymphoma staging, which
      guides patient management. Although positive staging marrow is defined as
      morphologically identifiable disease, such samples often also include flow
      cytometric analysis and conventional karyotyping. Cytogenetic analysis is a labor
      intensive and costly procedure and its utility in this setting is uncertain. We
      retrospectively reviewed pathological reports of 526 staging marrow specimens in
      which conventional karyotyping had been performed. All samples originated from a
      single institution from patients with previously untreated Hodgkin and non
      Hodgkin lymphomas presenting in an extramedullary site. Cytogenetic analysis
      revealed clonal abnormalities in only eight marrow samples (1.5%), all of which
      were positive for lymphoma by morphologic evaluation. Flow cytometry showed a
      small clonal lymphoid population in three of the 443 morphologically negative
      marrow samples (0.7%). Conventional karyotyping is rarely positive in lymphoma
      staging marrow samples and, in our cohort, the BM karyotype did not contribute
      clinically relevant information in the vast majority of cases. Our findings
      suggest that karyotyping should not be performed routinely on BM samples taken to
      stage previously diagnosed extramedullary lymphomas unless there is pathological
      evidence of BM involvement by lymphoma.

PMID- 25776297
TI  - Women-specific factors to consider in risk, diagnosis and treatment of
      cardiovascular disease.
AB  - In the era of individualized medicine, gaps in knowledge remain about sex
      specific risk factors, diagnostic and treatment options that might reduce
      mortality from cardiovascular disease (CVD) and improve outcomes for both women
      and men. In this review, contributions of biological mechanisms involving the sex
      chromosomes and the sex hormones on the cardiovascular system will be discussed
      in relationship to the female-specific risk factors for CVD: hypertensive
      disorders of pregnancy, menopause and use of hormonal therapies for contraception
      and menopausal symptoms. Additionally, sex-specific factors to consider in the
      differential diagnosis and treatment of four prevalent CVDs (hypertension,
      stroke, coronary artery disease and congestive heart failure) will be reviewed
      with emphasis on areas where additional research is needed. 

PMID- 25776303
TI  - Copolymer Networks From Oligo(epsilon-caprolactone) and n-Butyl Acrylate Enable a
      Reversible Bidirectional Shape-Memory Effect at Human Body Temperature.
AB  - Exploiting the tremendous potential of the recently discovered reversible
      bidirectional shape-memory effect (rbSME) for biomedical applications requires
      switching temperatures in the physiological range. The recent strategy is based
      on the reduction of the melting temperature range (DeltaT m ) of the actuating
      oligo(epsilon-caprolactone) (OCL) domains in copolymer networks from OCL and n
      butyl acrylate (BA), where the reversible effect can be adjusted to the human
      body temperature. In addition, it is investigated whether an rbSME in the
      temperature range close or even above Tm,offset (end of the melting transition)
      can be obtained. Two series of networks having mixtures of OCLs reveal broad
      DeltaTm s from 2  degrees C to 50  degrees C and from -10  degrees C to 37 
      degrees C, respectively. In cyclic, thermomechanical experiments the rbSME can be
      tailored to display pronounced actuation in a temperature interval between 20 
      degrees C and 37  degrees C. In this way, the application spectrum of the rbSME
      can be extended to biomedical applications. 

PMID- 25776339
TI  - The role of anxiety sensitivity in the relationship between posttraumatic stress
      symptoms and negative outcomes in trauma-exposed adults.
AB  - BACKGROUND: The development of posttraumatic stress symptoms (PTSs) following a
      trauma is related to impairment, diminished quality of life, and physical health
      issues. Yet it is not clear why some trauma-exposed individuals experience
      negative outcomes while others do not. The purpose of this study was to determine
      the role of several influential factors related to PTS severity and negative
      outcomes. METHODS: One hundred and twenty-two trauma-exposed adults were
      administered the following self-report measures: the Posttraumatic Stress
      Disorder Checklist-Civilian, the Trauma History Questionnaire-Short, the Anxiety
      Sensitivity Index-3, Depression and Anxiety Stress Scale 21, Sheehan Disability
      Scale, World Health Organization Quality of Life-BREF, and an abbreviated Patient
      Health Questionnaire. PRIMARY RESULTS: PTS severity was positively correlated
      with depressive symptom severity (r = 0.54, p < 0.001), chronicity of the most
      distressing trauma (r = 0.21, p = 0.017), and number of traumas (r = 0.22, p =
      0.012). Main effects were found for PTS severity (beta = -0.38, p < 0.01) and
      anxiety sensitivity (AS; beta = -0.39, p < 0.01) on quality of life. No
      interaction was found between PTS severity and AS with any negative outcome. PTS
      severity mediated the relationship between AS and physical health issues (0.05;
      95% CI: 0.02-0.08). CONCLUSION: This study helps clarify the role of various
      factors in the relationship between trauma and negative outcomes. Clinical and
      research implications are discussed.

PMID- 25776340
TI  - Chlorine resistant glutaraldehyde crosslinked polyelectrolyte multilayer
      membranes for desalination.
AB  - Crosslinked polyelectrolyte multilayer membranes are synthesized with salt
      rejection values approaching those of commercial desalination membranes, but with
      increased chlorine resistance. The membranes are fabricated directly onto porous
      commercial substrates. Subsequent crosslinking of the polycation layers with
      glutaraldehyde leads to NaCl rejections of up to 97%, while the incorporation of
      a highly sulfonated polysulfone polyanion leads to high chlorine resistance. 

PMID- 25776341
TI  - Annual meeting of the EpiGeneSys Network of Excellence--Advancing epigenetics
      towards systems biology.

PMID- 25776342
TI  - Topiramate use during pregnancy and major congenital malformations in multiple
      populations.
AB  - BACKGROUND: We measured birth prevalence of major congenital malformations (MCMs)
      after topiramate use during pregnancy to screen for a possible signal of
      increased risk. METHODS: Using four healthcare databases, we identified three
      cohorts of pregnant women: cohort 1, used topiramate during the first trimester;
      cohort 2, used topiramate or another antiepileptic drug previously but not during
      pregnancy; and cohort 3, were pregnant and did not use topiramate but had
      indications for use individually matched to those of users. Cohort 1 was compared
      with cohorts 2 and 3. MCMs were a code for any major congenital malformation
      dated within 30 days of the delivery date on the mother's claims or within 365
      days after infant birth date, excluding a genetic or syndromic basis, and with
      procedure or healthcare usage consistent with the MCM diagnosis code in the 365
      days after infant birth. RESULTS: Of the 10 specific common MCMs evaluated, 1
      (conotruncal heart defects) had a prevalence ratio greater than 1.5 for both
      primary comparisons, and 4 (ventricular septal defect, atrial septal defect,
      hypospadias, coarctation of the aorta) had a prevalence ratio greater than 1.5
      for one of the two comparisons. Following screening of organ systems with
      elevated MCMs, the prevalence ratio was greater than 1.5 for patent ductus
      arteriosus in both comparisons and for obstructive genitourinary defects in one
      comparison. CONCLUSION: To evaluate a large number of MCMs across many
      pregnancies, we used crude methods for detecting potential signals. Therefore,
      these results should be seen as potential signals, not causal.

PMID- 25776343
TI  - Feel the Fatigue and Be Active Anyway: Physical Activity on High-Fatigue Days
      Protects Adults With Arthritis From Decrements in Same-Day Positive Mood.
AB  - OBJECTIVE: The present study examined whether daily physical activity moderated
      the within-person relationship between daily fatigue and positive or negative
      mood in patients with rheumatoid arthritis (RA) or osteoarthritis (OA). METHODS:
      Participants were 142 patients, 70 with RA and 72 with OA (67.6% women).
      Participants completed daily diaries during 4 fixed time windows per day for 7
      days. Each diary assessed fatigue, pain, and positive and negative mood.
      Participants wore pedometers throughout each day and recorded pedometer readings
      at the end of each day. RESULTS: Physical activity buffered the same-day
      relationship between daily fatigue and positive mood for both RA and OA
      participants. On high-fatigue days, large decrements in mood were noted, but this
      was mitigated on days when participants were more physically active. CONCLUSION:
      Being more physically active on high-fatigue days buffered the negative effect of
      fatigue on positive mood among adults with both OA and RA. These findings have
      implications for understanding the daily variations in fatigue and inform
      potential clinical interventions.

PMID- 25776344
TI  - Family Functioning and Dysfunctional Eating Among Italian Adolescents: The
      Moderating Role of Gender.
AB  - The first aim of this study was to examine the association between different
      dimensions of family functioning and dysfunctional eating in a sample of Italian
      adolescent boys and girls. The second aim was to investigate whether gender
      moderates the relationship between family functioning and dysfunctional eating.
      Seven hundred and twenty seven adolescents (500 boys and 227 girls) with ages
      ranging from 15 to 18 years completed a survey of self-report measures. Findings
      from hierarchical multiple regression analysis suggested that aspects of family
      functioning such as flexibility, cohesion, disengagement, enmeshment, rigidity
      and chaotic were related to dysfunctional eating in adolescents. Additionally the
      results indicated differences between boys and girls, in particular dysfunctional
      eating in adolescent boys seemed to be more affected by dimensions of enmeshment
      and disengagement than dysfunctional eating in girls. This research highlights
      the important role of various aspects of family functioning in relation to
      dysfunctional eating in adolescents. 

PMID- 25776345
TI  - (14) N nuclear quadrupole resonance study of piroxicam: confirmation of new
      polymorphic form V.
AB  - A new polymorphic crystal form of piroxicam was discovered while preparing
      crystalline samples of piroxicam for (14) N nuclear quadrupole resonance (NQR)
      analysis. The new crystal form, designated as V, was prepared by evaporative
      recrystallization from dichloromethane. Three known polymorphic forms (I, II, and
      III) were also prepared. Our aim was to apply (14) N NQR to characterize the new
      polymorphic form of piroxicam and compare the results with those of the other
      known polymorphic forms. Additional analytical methods used for characterization
      were X-ray powder diffraction (XRPD), thermal analysis, and vibrational
      spectroscopy. For the first time, a complete set of nine characteristic (14) N
      NQR frequencies was found for each prepared polymorph of piroxicam. The
      consistent set of measured frequencies and calculated characteristic quadrupole
      parameters found for the new polymorphic form V is a convincing evidence that we
      are dealing with a new form. The already known piroxicam polymorphic forms were
      characterized similarly. The XRPD results were in accordance with the conclusions
      of (14) N NQR analysis. The performed study clearly demonstrates a strong
      potential of (14) N NQR method to be applied as a highly discriminative
      spectroscopic analytical tool to characterize polymorphic forms.

PMID- 25776435
TI  - Female sterility associated with increased clonal propagation suggests a unique
      combination of androdioecy and asexual reproduction in populations of Cardamine
      amara (Brassicaceae).
AB  - BACKGROUND AND AIMS: The coexistence of hermaphrodites and female-sterile
      individuals, or androdioecy, has been documented in only a handful of plants and
      animals. This study reports its existence in the plant species Cardamine amara
      (Brassicaceae), in which female-sterile individuals have shorter pistils than
      seed-producing hermaphrodites. METHODS: Morphological analysis, in situ manual
      pollination, microsatellite genotyping and differential gene expression analysis
      using Arabidopsis microarrays were used to delimit variation between female
      sterile individuals and hermaphrodites. KEY RESULTS: Female sterility in C. amara
      appears to be caused by disrupted ovule development. It was associated with a 2.4
      to 2.9-fold increase in clonal propagation. This made the pollen number of
      female-sterile genets more than double that of hermaphrodite genets, which
      fulfils a condition of co-existence predicted by simple androdioecy theories.
      When female-sterile individuals were observed in wild androdioecious populations,
      their ramet frequencies ranged from 5 to 54 %; however, their genet frequencies
      ranged from 11 to 29 %, which is consistent with the theoretically predicted
      upper limit of 50 %. CONCLUSIONS: The results suggest that a combination of
      sexual reproduction and increased asexual proliferation by female-sterile
      individuals probably explains the invasion and maintenance of female sterility in
      otherwise hermaphroditic populations. To our knowledge, this is the first report
      of the coexistence of female sterility and hermaphrodites in the Brassicaceae.

PMID- 25776436
TI  - Comparability of sociodemographic and pregnancy characteristics of pregnancy
      related deaths identified via the sisterhood method versus the household/verbal
      autopsy method.
AB  - OBJECTIVE: To compare sociodemographic and pregnancy characteristics of pregnancy
      related deaths identified by the direct sisterhood and the verbal autopsy with
      household mortality (HHVA) methods. METHODS: Nationally representative data for
      1997-2001 were obtained from the household, verbal autopsy, and women's
      questionnaires of the Bangladesh Maternal Health Services and Maternal Mortality
      Services Survey, 2001. Sociodemographic and pregnancy characteristics were
      compared for maternal deaths identified by the two methods. Characteristics of
      deceased women were reported directly with HHVA, but extrapolated in the direct
      sisterhood method using the reporting sister as proxy. RESULTS: Overall, 201
      pregnancy-related deaths were identified via HHVA and 388 through DS reporting.
      There were no significant differences between reporting sister characteristics
      and deceased women's characteristics in educational attainment, working status,
      husband's educational attainment, and spouse educational parity. However, timing
      of death relative to pregnancy phase, number of previous live births, and years
      since death did differ (P<0.05). CONCLUSION: The sociodemographic characteristics
      of women with pregnancy-related deaths identified via the two methods were
      similar. However, some pregnancy characteristics differed significantly,
      suggesting that different policy interventions are required. Before considering
      using sister proxy characteristics to target services, issues responsible for
      these differences should be resolved, and generalizability of evaluated
      indicators must be considered.

PMID- 25776437
TI  - Improving cardiovascular health of underserved populations in the community with
      Life's Simple 7.
AB  - PURPOSE: The purpose of this nurse practitioner (NP) led initiative was to
      improve the cardiovascular health of two underserved populations in the community
      using the American Heart Association (AHA) Life's Simple 7 and My Life Check
      (MLC) tools. DATA SOURCES: Two inner city community sites were targeted: (a) a
      senior center servicing African American (AA) older adults, and (b) a residential
      facility servicing homeless women. Preprogram health data (blood pressure,
      cholesterol, blood glucose levels, body mass index, and health behaviors) were
      collected to calculate MLC scores. Postprogram health data were obtained on
      participants with the lowest MLC scores who completed the program. CONCLUSIONS:
      Eight older adults completed the program with a 37.1% increase in average MLC
      score (6.2 vs. 8.5). Ten women completed the program with a 9.3% decrease in
      average MLC score (4.3 vs. 3.9). Favorable benefits were observed in the AA older
      adults. In contrast, similar benefits were not observed in the women, which may
      be because of a constellation of social, environmental, biological, and mental
      health factors. IMPLICATIONS FOR PRACTICE: NPs are prepared to target community
      based settings to address the health of underserved populations. Engaging key
      stakeholders in the planning and implementation is essential for success.

PMID- 25776438
TI  - Review of anal cancer patients at the Ottawa hospital.
AB  - BACKGROUND: Anal cancer is uncommon. We reviewed the treatment and outcomes of
      anal cancer patients in a population referred to the Ottawa Hospital Cancer
      Centre (TOHCC) over a 12-year period. METHODS: A chart review was conducted with
      patient data collected from hospital records, including: demographic, treatment
      and outcome information. Outcomes of interest included: overall survival (OS),
      disease free survival (DFS), and colostomy free survival (CFS). RESULTS: 180
      patients were included in the study population. 72% (n = 130) female and 28% (n =
      50) male. 6.7% (n = 12 males) of patients were HIV positive - all were on anti
      retroviral therapy. 60% (n = 108) of patients were ever-smokers, mean patient age
      was 62 [range 35-90] years. The most frequent presenting symptoms were blood per
      rectum and anal pain. Treatment intent was curative in 87%. Treatment included
      radiotherapy (94%), brachytherapy (26%), chemotherapy (73%). Among patients
      treated with curative-intent, 72% had a complete response, 31% had local/regional
      recurrence, 16% required salvage surgery and 21% had distant recurrence. The
      colostomy rate was 23%. 5 year overall survival (OS) was not significantly
      different for patients by HIV status. Survival was superior if MMC-FU was used
      first vs. CIS-FU; OS HR 0.47 (0.24-0.94), p < 0.033. CONCLUSIONS: The outcomes of
      patients in this large retrospective cohort study are similar to the outcomes of
      patients in highly selective clinical trials. Five year overall survival and
      colostomy free survival are encouraging. MMC-FU was found to be superior to CIS
      FU.

PMID- 25776439
TI  - Progress in biotechnology: EuroBiotech 2014.

PMID- 25776440
TI  - F-18 fluorodeoxyglucose positron emission tomography can detect early response to
      adalimumab, a tumor necrosis factor-alpha antagonist, in rheumatoid arthritis: A
      prospective pilot study.

PMID- 25776441
TI  - Rituximab therapy for ankylosing spondylitis associated to demyelinating disease
      of the central nervous system.

PMID- 25776442
TI  - Intra-articular injections in thumb osteoarthritis: A systematic review and meta
      analysis of randomized controlled trials.
AB  - OBJECTIVES: The objective was to assess the efficacy of intra-articular
      injections of corticosteroids or hyaluronic acid in thumb osteoarthritis.
      METHODS: A systematic review of the literature was performed until August 2014.
      All controlled trials reporting the efficacy on pain, functional capacity and
      pulp pinch force of hyaluronic acid or corticosteroids in thumb osteoarthritis
      were selected. Pooled standardized response means (SRMs) were assessed by meta
      analysis. RESULTS: Six trials were included and contributed to 3 meta-analyses
      (hyaluronic acid versus placebo, corticosteroids vs. placebo and hyaluronic acid
      vs. corticosteroids). Among the 428 patients included, 169 were treated with
      hyaluronic acid, 147 with corticosteroids and 74 with placebo. Versus placebo at
      week 12, hyaluronic acid (2 trials, 148 patients) lead to better functional
      capacity (SRM -1.14 [-1.69; -0.60]) with no difference on pain; corticosteroids
      (2 trials, 164 patients) lead to no difference on pain or function. When
      comparing hyaluronic acid vs. corticosteroids (4 trials, 304 patients), no
      difference was evidenced until week 12. At week 24, pain was significantly lower
      in the corticosteroids group (SRM 1.44 [0.14; 2.74]) and pulp pinch force higher
      in the hyaluronic acid group (SRM -0.75 [-3.87; -1.97]). CONCLUSION: This meta
      analysis shows great heterogeneity. Hyaluronic acid may be useful to increase
      functional capacity and corticosteroids to decrease pain in thumb osteoarthritis
      at week 24.

PMID- 25776443
TI  - Uncommon localization of pathologic vertebral fracture in ankylosing spondylitis.

PMID- 25776444
TI  - Hyperuricemia starts at 360 micromoles (6 mg/dL).

PMID- 25776445
TI  - Assessment and effective targeting of Interleukin-1 in multicentric
      reticulohistyocytosis.
AB  - Multicentric reticulohistyocytosis (MRH) is a rare multisystemic non-Langerhans
      histiocytosis characterized by cutaneous nodules and severe destructive
      polyarthritis, sometimes associated with constitutional symptoms and various
      organ involvements. Its treatment remains empirical and challenging. We first
      report herein, the successful treatment of a multicentric reticulohistiocytosis
      patient with anakinra based on cutaneous biopsy immunostaining and serum
      cytokines features. A first-line treatment associating methotrexate, cortisone
      and hydoxychloroquine showed none improvement. Therefore, while further tests
      were performed to rule out an associated malignancy, auto-immune disease or
      mycobacterial infection, a treatment with anakinra was chosen instead of anti-TNF
      alpha drugs. As soon as the 5th day, anakinra allowed control of fever, then
      rapid improvement of constitutional symptoms, arthritis, cutaneous lesions, and
      normalization of C-reactive protein, IL-6, and especially IL-1beta levels. Then
      methotrexate was added, while anakinra was removed at the 12th month, with
      persistent and complete remission over the two-year follow up. Further assessment
      of IL-1 pathogenic role and blockade on larger cohorts of patient could open new
      therapeutic perspectives for refractory/relapsing MRH, considering the good
      tolerance profile of specific targeting drugs. 

PMID- 25776446
TI  - A swollen thigh and knee pain in a cerebral palsy child - Scurvy.

PMID- 25776447
TI  - Measurable definitions of ankylosing spondylitis management recommendations are
      needed for use in observational studies.

PMID- 25776448
TI  - Benign rheumatoid nodulosis.

PMID- 25776449
TI  - Therapeutic patient education: From infantilization to critical thinking.

PMID- 25776450
TI  - New onset of articular inflammatory manifestations in patients with hidradenitis
      suppurativa under treatment with infliximab.
AB  - OBJECTIVES: Severe hidradenitis suppurativa (HS), under infliximab, can be
      associated with different forms of arthritis whose mechanism is unclear. Our
      objective is to establish the frequency and clinical presentation of new-onset
      arthritis in HS under infliximab. METHODS: Severe HS patients under infliximab
      were followed up between 2007-2012. New articular inflammatory manifestations
      were investigated by rheumatologist. RESULTS: Three patients over eleven
      developed a polyarthritis. Mean duration of arthritis was 3 months. At
      treatment's stop: 2 patients improved and 1 relieved with adalimumab. CONCLUSION:
      The inflammatory rheumatism's frequency in HS under infliximab seems
      underestimated.

PMID- 25776451
TI  - Understanding placebo effects in rheumatology.

PMID- 25776452
TI  - Portable hemoglobinometer is a reliable technology for the follow-up of
      venesections tolerance in hemochromatosis.
AB  - BACKGROUND: The treatment of HFE-related hemochromatosis, one of the most common
      genetic diseases, is based on phlebotomies whose tolerance is evaluated by
      regular monitoring of hemoglobin. Using a portable hemoglobinometer (PH) could
      provide an easy and fast determination of hemoglobin. Therefore, the aim of the
      present study was to compare, in hemochromatosis patients treated by
      bloodletting, the hemoglobin concentrations as assayed, on capillary blood, by a
      PH device and, on venous blood, by a cell counter (CC) device. METHODS: For a
      total period of 12 weeks duration, all patients undergoing phlebotomies in the
      same hospital outpatient unit had hemoglobin determinations both by the HemoCue
      and by the laboratory's DxH 800 Coulter. To evaluate the sensitivity and
      specificity of the HemoCue, patients were classified as presenting or not anemia
      as defined by hemoglobin level below 11 g/dl. RESULTS: Measurements of hemoglobin
      were performed in 122 patients. The sensitivity and specificity of PH compared to
      CC were 100 and 98.1%, respectively. Capillary hemoglobin by PH slightly
      underestimated venous hemoglobin by CC. The Pearson's correlation coefficient
      between PH and CC was 0.80 (P<0.0001). CONCLUSION: PH is a reliable, quick and
      easy technology, which can be proposed to follow-up the tolerance of venesections
      in hemochromatosis patients.

PMID- 25776453
TI  - Temperature-dependent drug release from DPPC:C12H25-PNIPAM-COOH liposomes:
      control of the drug loading/release by modulation of the nanocarriers'
      components.
AB  - Novel polymer-modified thermosensitive liposomes were developed for the delivery
      of indomethacin in order to control its release profile. When attached to 1,2
      dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) liposomes, the end functionalized
      C12H25-poly(N-isopropylacrylamide)-COOH (C12H25-PNIPAM-COOH) polymer was membrane
      disruptive in a temperature-dependent manner. The interest for this polymer is
      driven by its famous lower critical solution temperature (LCST) behavior, where
      heating an aqueous solution of PNIPAM above 32 degrees C induces nanophase
      separation and polymer chain aggregation. The physicochemical/structural behavior
      of these polymer-modified thermosensitive liposomes was found to depend on the
      PNIPAM:lipid molar ratio and the composition of the polymeric guest. The
      incorporation of PNIPAM has caused alterations in the thermotropic behavior of
      DPPC liposomes, as the differential scanning calorimetry (DSC) experiments
      revealed. The drug loading and the release were found to be strongly dependent on
      the thermotropic characteristics of the PNIPAM grafted DPPC liposomes. Namely,
      the in vitro release is immediate at 37 degrees C (>LCST) ("burst" effect), while
      the prepared mixed nanocarriers did not release the encapsulated bioactive
      substance at <32 degrees C (<LCST). Thus, the thermosensitivity and the drug
      loading/release properties of the prepared formulations can be modulated by
      varying the ratio of DPPC/PNIPAM components, as well as the molecular
      characteristics of the polymeric guest.

PMID- 25776454
TI  - Impact of exercise stress testing on diagnostic gene expression in patients with
      obstructive and nonobstructive coronary artery disease.
AB  - A blood-based gene expression test can diagnose obstructive coronary artery
      disease (CAD). The test is sensitive to inflammatory and immune processes
      associated with atherosclerosis. Acute exercise engages short-term inflammatory
      pathways, and exercise stress testing may affect results of gene expression
      testing during the same diagnostic workup. The objective of this study was to
      evaluate the effect of exercise on diagnostic gene expression testing. Ten
      patients with obstructive CAD (>=50% stenosis) and 10 with no/minimal CAD (<=20%
      stenosis) were identified by angiography. Blood samples for gene expression were
      obtained at baseline, peak exercise, 30 to 60 minutes after testing, and 24 to 36
      hours after testing. Core-lab gene expression analysis yielded raw gene
      expression scores (GES) for each time point. Linear models were used to estimate
      changes in GES, adjusting for CAD status and other covariates. GES increased
      during peak exercise across both genders, with no significant differences as a
      function of CAD status. The overall adjusted mean GES increase at peak exercise
      was 0.29 (95% confidence interval 0.22 to 0.36; p <0.001). GES after exercise
      were not significantly different from baseline. The change in gene expression
      levels during peak exercise may reflect a transient inflammatory response to
      acute exercise that may be independent of patient gender or CAD status. In
      conclusion, CAD GES increase at peak exercise testing and rapidly return to
      baseline. Such may reflect a transient inflammatory response to acute exercise
      independent of gender or extent of CAD.

PMID- 25776455
TI  - Relation of nonalcoholic fatty liver disease and Framingham Risk Score to flow
      mediated dilation in patients with cardiometabolic risk factors.
AB  - Nonalcoholic fatty liver disease (NAFLD) has a high prevalence in the general
      population. Brachial artery flow-mediated dilation (FMD) is a surrogated marker
      of early atherosclerosis. Few data investigating the relation between FMD, NAFLD,
      and cardiovascular (CV) risk are available. We recruited 367 consecutive
      outpatients with cardiometabolic risk factors who underwent ultrasound scanning
      for liver steatosis and FMD. Mean age was 54.2 +/- 12.2 years, and 37% were
      women. NAFLD was present in 281 patients (77%). Median FMD was 5.1%. FMD was
      significantly reduced in patients with NAFLD (p <0.001), diabetes (p = 0.001),
      history of coronary heart disease (p = 0.034), and metabolic syndrome (p = 0.050)
      and in those taking antihypertensive drugs (p = 0.022). Women disclosed greater
      FMD than males (p = 0.033). Moreover, FMD inversely correlated with age (Spearman
      rank correlation test [Rs], -0.171; p = 0.001), waist circumference (Rs, -0.127;
      p = 0.016), fasting blood glucose (Rs, -0.204; p <0.001), and gamma-glutamyl
      transpeptidase (Rs, -0.064; p = 0.234). At multivariate regression analysis,
      fasting blood glucose (beta, -0.148; p = 0.008), age (beta, -0.158; p = 0.005),
      and the presence of NAFLD (beta, -0.132; p = 0.016) inversely correlated with
      FMD, whereas female gender predicted a better FMD (beta, 0.125; p = 0.022). FMD
      and Framingham Risk Score (FRS) were inversely correlated (Rs, -0.183; p <0.001).
      After dividing patients into low (FRS <10; FMD, 5.5% [3.1% to 8.9%]),
      intermediate (FRS 10 to 20; FMD, 4.9% [2.7% to 7.5%]), and high (FRS >20; FMD,
      3.3% [1.7% to 4.5%]) risk, FMD significantly decreased across risk classes of FRS
      (p = 0.003). At multivariate regression analysis, both FRS (beta, -0.129; p =
      0.016) and NAFLD (beta, -0.218; p <0.001) were variables independently associated
      with FMD. In conclusion, the presence of NAFLD and FRS inversely correlated with
      FMD.

PMID- 25776456
TI  - Prevalence and impact of pulmonary hypertension on patients with aortic stenosis
      who underwent transcatheter aortic valve replacement.
AB  - Limited amount of data suggest that patients with aortic stenosis and pulmonary
      hypertension (PH) who undergo transcatheter aortic valve replacement (TAVR)
      experience decrease in PH postprocedure. Inconsistent use of systolic pulmonary
      artery pressure cut-off values in previous studies limits our ability to draw
      meaningful conclusions regarding the prognostic role of PH in assessment of TAVR
      candidates. A total of 415 consecutive patients who underwent TAVR were included
      in the present study. Two groups were compared based on receiver-operating
      characteristics curve analysis for the best SPAP value to predict outcome,
      yielding 2 study groups of no/mild PH (<=50 mm Hg; n = 172, 41%) versus
      moderate/severe PH (>50 mm Hg; n = 243, 59%). Demographics and co-morbidities
      were comparable between the 2 groups; however, right-sided cardiac failure (35%
      vs 19.8%, p = 0.02) and mitral regurgitation (18.4% vs 8.6%, p = 0.007) were more
      frequent in patients with moderate/severe PH. Procedural characteristics and
      complications were comparable between the groups. Although there was an early
      overall decrease in SPAP postprocedure, only 26% of moderate/severe patients with
      PH experienced a significant decrease in SPAP (>10 mm Hg). The 30-day (14.5% vs
      7.4%, p = 0.02) and 1-year mortality (30.8% vs 21%, p = 0.02) was higher in
      moderate/severe patients with PH. In multivariate analysis, systolic pulmonary
      artery pressure and chronic lung disease were identified as independent
      predictors for mortality at 1 year. PH is a frequent co-morbidity in patients
      with severe aortic stenosis who underwent TAVR. Significantly elevated pulmonary
      artery pressures at baseline may serve as a poor prognostic factor when
      performing preprocedural assessment of the patients.

PMID- 25776457
TI  - Glycoprotein IIb/IIIa Receptor Inhibitors in Combination With Vorapaxar, a
      Platelet Thrombin Receptor Antagonist, Among Patients With Non-ST-Segment
      Elevation Acute Coronary Syndromes (from the TRACER Trial).
AB  - We evaluated the interaction between protease-activated receptor-1 antagonist
      vorapaxar and concomitant glycoprotein (GP) IIb/IIIa receptor inhibitors in
      patients with non-ST-segment elevation acute coronary syndromes who underwent
      PCI. In Thrombin Receptor Antagonist for Clinical Event Reduction in Acute
      Coronary Syndrome trial, 12,944 patients with non-ST-segment elevation acute
      coronary syndromes were randomized to vorapaxar or placebo. Administration of GP
      IIb/IIIa receptor inhibitors was allowed at the treating physician's discretion.
      We investigated whether use of GP IIb/IIIa receptor inhibitors modified
      vorapaxar's effect on non-coronary artery bypass grafting (CABG)-related bleeding
      at 7 days and ischemic events at 30 days. In total, 7,455 patients underwent PCI
      during index hospitalization. Of these, 2,023 patients (27.1%) received
      inhibitors and 5,432 (72.9%) did not. Vorapaxar was associated with a numerically
      higher rate of non-CABG-related moderate/severe Global Use of Strategies to Open
      Occluded Arteries (GUSTO) bleeding at 7 days compared with placebo in those who
      did (1.3% vs 1.0%) and did not (0.6% vs 0.4%) receive GP IIb/IIIa receptor
      inhibitors. Ischemic end point rates at 30 days were not significantly lower with
      vorapaxar versus placebo. Increased rates of non-CABG GUSTO moderate/severe
      bleeding were observed in patients who received GP IIb/IIIa receptor inhibitors
      versus those who did not (adjusted hazard ratio [HR] 1.77, 95% confidence
      interval [CI] 0.43 to 7.35 in placebo arm; adjusted HR 2.02, 95% CI 0.62 to 6.61
      in vorapaxar arm) and in those who received vorapaxar versus placebo (adjusted HR
      1.54, 95% CI 0.36 to 6.56 in the GP IIb/IIIa group; adjusted HR 1.34, 95% CI 0.44
      to 4.07 in the no-GP IIb/IIIa group). No interaction was found between vorapaxar
      and inhibitor use up to 7 days (P interaction = 0.89) nor at the end of the
      treatment (P interaction = 0.74); however, the event rate was low. Also, no
      interaction was observed for efficacy end points after PCI at 30 days or at the
      end of the treatment. In conclusion, GP IIb/IIIa receptor inhibitor use plus dual
      antiplatelet therapy in a population with non-ST-segment elevation myocardial
      infarction planned for PCI was frequent but did not interact with vorapaxar's
      efficacy or safety. Nonetheless, GP IIb/IIIa receptor inhibitors and vorapaxar
      were associated with increased bleeding risk, and their combined use may result
      in additive effects on bleeding rates.

PMID- 25776458
TI  - Myrosinase-treated glucoerucin is a potent inducer of the Nrf2 target gene heme
      oxygenase 1--studies in cultured HT-29 cells and mice.
AB  - In this study, the effect of myrosinase-treated glucoerucin (GER+MYR), which
      releases the isothiocyanate (ITC) erucin, on heme oxygenase 1 (HO-1) gene
      expression and Nrf2 signaling was investigated in vitro in cultured cells and in
      vivo in mice. Treatment of HT-29 cells with GER+MYR resulted in a significant
      increase in the mRNA and protein levels of nuclear Nrf2 and HO-1. GER+MYR was
      more potent at enhancing the nuclear Nrf2 levels than were the following
      myrosinase-treated glucosinolates: sinigrin, glucoraphanin and gluconasturtiin,
      which are the precursors of allyl-ITC, R-sulforaphane and 2-phenylethyl ITC,
      respectively. GER+MYR also significantly induced HO-1 gene expression in the
      mouse intestinal mucosae and liver but not in the brain. Mechanistic studies
      suggest that GER+MYR induces Nrf2 via ERK1/2-, p38- and JNK-dependent signal
      transduction pathways. The GER+MYR-mediated increase in HO-1 expression is
      primarily attributable to p38 signaling. 

PMID- 25776459
TI  - Intake of farmed Atlantic salmon fed soybean oil increases hepatic levels of
      arachidonic acid-derived oxylipins and ceramides in mice.
AB  - Introduction of vegetable ingredients in fish feed has affected the fatty acid
      composition in farmed Atlantic salmon (Salmo salar L). Here we investigated how
      changes in fish feed affected the metabolism of mice fed diets containing fillets
      from such farmed salmon. We demonstrate that replacement of fish oil with
      rapeseed oil or soybean oil in fish feed had distinct spillover effects in mice
      fed western diets containing the salmon. A reduced ratio of n-3/n-6
      polyunsaturated fatty acids in the fish feed, reflected in the salmon, and hence
      also in the mice diets, led to a selectively increased abundance of arachidonic
      acid in the phospholipid pool in the livers of the mice. This was accompanied by
      increased levels of hepatic ceramides and arachidonic acid-derived pro
      inflammatory mediators and a reduced abundance of oxylipins derived from
      eicosapentaenoic acid and docosahexaenoic acid. These changes were associated
      with increased whole body insulin resistance and hepatic steatosis. Our data
      suggest that an increased ratio between n-6 and n-3-derived oxylipins may
      underlie the observed marked metabolic differences between mice fed the different
      types of farmed salmon. These findings underpin the need for carefully
      considering the type of oil used for feed production in relation to salmon
      farming. 

PMID- 25776460
TI  - Concentrations of the adrenocorticotropic hormone, corticosterone and sex steroid
      hormones and the expression of the androgen receptor in the pituitary and adrenal
      glands of male turkeys (Meleagris gallopavo) during growth and development.
AB  - Androgens take part in the regulation of puberty and promote growth and
      development. They play their biological role by binding to a specific androgen
      receptor (AR). The aim of this study was to evaluate the expression of AR mRNA
      and protein in the pituitary and adrenal glands, to localize AR protein in
      luteinizing hormone (LH)-producing pituitary and adrenocortical cells, to
      determine plasma concentrations of adrenocorticotropic hormone (ACTH) and
      corticosterone and the concentrations of corticosterone, testosterone (T),
      androstenedione (A4) and oestradiol (E2) in the adrenal glands of male turkeys at
      the age of 4, 8, 12, 16, 20, 24 and 28weeks. The concentrations of hormones and
      the expression of AR varied during development. The expression of AR mRNA and
      protein in pituitary increased during the growth. The increase of AR mRNA levels
      in pituitary occurred earlier than increase of AR protein. The percentage of
      pituitary cells expressing ARs in the population of LH-secreting cells increased
      in week 20. It suggests that AR expression in LH-producing pituitary cells is
      determined by the phase of development. The drop in adrenal AR mRNA and protein
      expression was accompanied by an increase in the concentrations of adrenal
      androgens. Those results could point to the presence of a compensatory mechanism
      that enables turkeys to avoid the potentially detrimental effects of high
      androgen concentrations. Our results will expand our knowledge of the role of
      steroids in the development of the reproductive system of turkeys from the first
      month of age until maturity. 

PMID- 25776461
TI  - Feather corticosterone content in predatory birds in relation to body condition
      and hepatic metal concentration.
AB  - This study investigated the feasibility of measuring corticosterone in feathers
      from cryo-archived raptor specimens, in order to provide a retrospective
      assessment of the activity of the stress axis in relation to contaminant burden.
      Feather samples were taken from sparrowhawk Accipiter nisus, kestrel Falco
      tinnunculus, buzzard Buteo buteo, barn owl Tyto alba, and tawny owl Strix aluco
      and the variation in feather CORT concentrations with respect to species, age,
      sex, feather position, and body condition was assessed. In sparrowhawks only,
      variation in feather CORT content was compared with hepatic metal concentrations.
      For individuals, CORT concentration (pgmm(-1)) in adjacent primary flight
      feathers (P5 and P6), and left and right wing primaries (P5), was statistically
      indistinguishable. The lowest concentrations of CORT were found in sparrowhawk
      feathers and CORT concentrations did not vary systematically with age or sex for
      any species. Significant relationships between feather CORT content and condition
      were observed in only tawny owl and kestrel. In sparrowhawks, feather CORT
      concentration was found to be positively related to the hepatic concentrations of
      five metals (Cd, Mn, Co, Cu, Mo) and the metalloid As. There was also a negative
      relationship between measures of condition and total hepatic metal concentration
      in males. The results suggest that some factors affecting CORT uptake by feathers
      remain to be resolved but feather CORT content from archived specimens has the
      potential to provide a simple effects biomarker for exposure to environmental
      contaminants. 

PMID- 25776462
TI  - Sterile 'Judas' carp--Surgical sterilisation does not impair growth, endocrine
      and behavioural responses of male carp.
AB  - Use of 'Judas' fish to betray the locations of conspecifics is a powerful tool in
      management of invasive pest fish but poses a risk of contributing to recruitment.
      Our aim therefore was to generate surgically sterilised male common carp
      (Cyprinus carpio) and test whether they readily assimilate into wild populations,
      retain sexual behaviour and successfully betray the locations of feral carp. Male
      common carp were surgically sterilised (n=44) adopting a two-point nip technique,
      using either a haemoclip, suture or electro cautery to tie each of the testicular
      ducts about 2.5 cm cranial to urogenital sinus-retaining all of the glandular
      testis tissue. Observed survival (95%) and success (>70%) rates were relatively
      high. Plasma steroids (11-keto testosterone and 17beta-estradiol) were quantified
      by immunoassay. A subset of sterile and control male fish (n=7 each) were
      implanted with radio-transmitters and released into Lake Sorell (50 km(2)) and
      their ability to betray the location of feral carp was assessed by radio tracking
      and targeted fishing. There was a statistically significant difference in 11-keto
      testosterone and 17beta-estradiol levels over time (P<0.05), but not between the
      sterile and control groups within each sampling time (P>0.05), implying that
      surgery did not compromise the animals physiologically. The sterile Judas fish
      integrated well into the population-behaving similarly to control Judas males and
      assisted in the capture of feral carp. The study marks a significant breakthrough
      in the management of this pest fish with potential adoption to the management of
      other pest fish globally.

PMID- 25776463
TI  - Estrogen regulation of phosphoserine phosphatase during regression and
      recrudescence of female reproductive organs.
AB  - Phosphoserine phosphatase (PSPH) is a well-known mediator of l-serine
      biosynthesis in a variety of tissues and its dysregulation causes various
      diseases, specifically most cancers. However, little is known about the
      expression and hormonal regulation of PSPH gene in the female reproductive tract.
      Therefore, in the current study, we focused on relationships between PSPH
      expression and estrogen during growth, development, differentiation, remodeling
      and recrudescence of the chicken oviduct and in the progression of epithelial
      derived ovarian carcinogenesis in laying hens. The results revealed that PSPH
      mRNA and protein levels increased in the glandular (GE) and luminal epithelial
      (LE) cells in the developing oviduct of chicks treated with exogenous estrogen.
      Additionally, PSPH mRNA and protein expression was up-regulated in GE and LE of
      the oviduct in response to endogenous estrogen during the recrudescence phase
      after induced molting. Furthermore, PSPH mRNA and protein were predominantly
      detected in GE of cancerous, but not normal ovaries. In conclusion, PSPH is a
      novel estrogen-responsive gene involved in development of the oviduct of chicks
      and recrudescence of the oviduct of laying hens after molting. PSPH is also a
      potential target molecule that may help elucidate mechanism responsible for the
      progression of epithelial cell-derived ovarian carcinogenesis and be of use in
      therapeutic applications as a biomarker for early diagnosis of epithelial cell
      derived ovarian cancer in laying hen as well as women. 

PMID- 25776464
TI  - Effects of patellofemoral overstuffing on knee flexion and patellar kinematics
      following total knee arthroplasty: a cadaveric study.
AB  - PURPOSE: The purpose of this study was to test the hypothesis that overstuffing
      the patellofemoral joint during total knee arthroplasty (TKA) would decrease
      passive knee flexion and alter patellar kinematics during knee flexion. METHODS:
      Ten cadaveric knees were implanted with cruciate-retaining TKAs, and the
      patellofemoral joint was overstuffed in 2-mm increments with custom-augmented
      patellar prostheses (+2 mm through +8 mm). Changes to knee flexion, patellar
      shift, tilt and rotation were measured with an imageless optical-tracking
      computer navigation system. RESULTS: Knee flexion decreased an average 1.2
      degrees  with each additional 2 mm of patellar thickness. Compared with control
      TKA (+0 mm), no significant decrease in knee flexion was detected until the
      patellofemoral joint was overstuffed with the +8-mm patellar prosthesis.
      Kinematic tracking data showed significantly greater lateral shift of patella
      with the +6- and +8-mm prostheses and significantly greater lateral tilt with the
      +8-mm prosthesis. Overstuffing had no appreciable effect on patellar rotation.
      CONCLUSIONS: Passive knee flexion after TKA is significantly reduced when
      overstuffing the patellofemoral joint by +8 mm, and patellofemoral kinematics are
      altered when overstuffing the joint by +6 mm. These results demonstrate the
      relatively modest effects of patellofemoral overstuffing on knee flexion and
      patellar tracking kinematics after TKA.

PMID- 25776465
TI  - Surgical treatment of aseptic forearm nonunion with plate and opposite bone graft
      strut. Autograft or allograft?
AB  - PURPOSE OF THE STUDY: Adequate treatment of forearm nonunion should achieve both
      biological stimulation of the bone and mechanical stability. The use of bone
      graft could enhance the healing of a nonunion providing osteogenic,
      osteoconductive and osteoinductive stimulation and an optimal stability of the
      fixation. We retrospectively reviewed two cohorts of patients affected by forearm
      nonunion and treated with plate and opposite bone graft to determine whether the
      use of autograft versus allograft differs in terms of (1) rate of healing of the
      nonunion and (2) time of healing. MATERIALS AND METHODS: Thirty-four patients
      were treated for aseptic forearm nonunion with cortical graft strut with opposite
      plate and intercalary graft in case of segmental bone defect. In 20 patients an
      autograft harvest from the fibula (group A) and in 14 (group B) an allograft
      provided by the bone bank of our institution were used. RESULTS: All the
      nonunions healed in a mean of four months in both groups, ranging from two to 12
      months in group A and from three to ten months in group B. At the latest follow
      up forearm function and pain were satisfactory in both groups. CONCLUSION: The
      use of plate and opposite bone graft demonstrated to be effective in promoting
      the healing of forearm nonunions, without significant differences in terms of
      rate and time of healing in the two groups. Considering the higher surgical time
      and the comorbidity of the donor site, if a bone bank is available, we suggest to
      use homologous cortical bone strut graft with opposite plate and screw fixation
      for the treatment of aseptic forearm nonunion rather than autograft.

PMID- 25776466
TI  - Optimal management of immune-related toxicities associated with checkpoint
      inhibitors in lung cancer.
AB  - Antibodies against immune checkpoints including CTLA-4, PD-1 and PD-L1 are
      increasingly being used in lung cancer. They are associated with novel, immune
      related toxicities not previously encountered with established treatments for
      lung cancer including colitis, hepatitis, rashes, neuropathies and other rarer
      immune mediated toxicities. Although generally these are low grade, there is a
      potential to be life threatening if not managed promptly. Early recognition of
      toxicity and institution of management algorithms are key to ensuring patient
      safety. We review the common toxicities and provide recommendations on their
      management. 

PMID- 25776467
TI  - Characterization of platelet aggregation responses in microminipigs: Comparison
      with miniature pigs and the influence of dual antiplatelet administration of
      aspirin plus prasugrel.
AB  - We aimed to characterize platelet aggregation responses and the impact of dual
      antiplatelet therapy in microminipigs. In this in vitro study, both adenosine-5'
      diphosphate (ADP, 5-50MUM) and collagen (2-20MUg/ml) induced concentration
      related platelet aggregation in the microminipigs; 20MUM ADP and 5 and 12.5MUg/ml
      collagen were selected for further ex vivo studies. Aspirin plus prasugrel were
      administered orally for 7days (n=4/each group). Ex vivo platelet aggregation was
      analyzed on Day 1 (1 and 4h after administration), Day 4 (4h), and Day 7 (4h)
      under three different prasugrel dosing regimens: LD0/MD1 (1mg/kg/day), LD0/MD3
      (3mg/kg/day), and LD10/MD1 (10mg/kg loading dose and 1mg/kg/day maintenance
      dose). Aspirin (10mg/kg/day) was administered to all groups. In the presence of
      aspirin, prasugrel at 3 and 10mg/kg significantly inhibited ADP-induced platelet
      aggregation on Day 1. On Days 4 and 7, significant inhibition of platelet
      aggregation (IPA) was also observed in each group. With 5MUg/ml collagen-induced
      platelet aggregation, all three groups showed significant IPA at 4h on Day 1 or
      later. In 12.5MUg/ml collagen-induced platelet aggregation, all groups showed
      significant effects on Days 4 and 7; however, the 30%-35% IPA was considerably
      lower than that (50%-60%) found with 5MUg/ml collagen. In Clawn miniature pigs,
      similar inhibitory patterns were observed for both ADP- and collagen-induced ex
      vivo platelet aggregation. In conclusion, these results indicated that
      microminipigs as well as miniature pigs may represent useful experimental animals
      for thrombosis research. 

PMID- 25776468
TI  - Anticoagulation for stroke prevention in new atrial fibrillation after coronary
      artery bypass graft surgery.
AB  - BACKGROUND: The benefit of early anticoagulation for stroke prophylaxis in atrial
      fibrillation after coronary artery bypass graft (CABG) surgery is uncertain. We
      therefore studied what proportion of ischemic strokes in patients with atrial
      fibrillation early after CABG surgery were potentially preventable by
      anticoagulation with warfarin. METHODS: We reviewed medical records from 2264
      patients with isolated CABG performed during a period when our institution had no
      policy on anticoagulation for postoperative atrial fibrillation. The outcome was
      ischemic stroke within 30days postoperatively and verified with computed
      tomography (CT) in patients with new postoperative atrial fibrillation for more
      than 48h. RESULTS: New, postoperative atrial fibrillation occurred in 403 (17.8%)
      of the patients and 191 of those (47.4%) were not started on warfarin at 48hours.
      Eight patients developed CT-verified ischemic stroke, which occurred on
      postoperative day 1-3 in 4 patients and in 3 patients was of the lacunar type. In
      two patients (stroke day 25 and day 30) warfarin could have been preventive. In
      another patient with onset of neurological symptoms on postoperative day 8 (4days
      from onset of the arrhythmia), systemic anticoagulation might have limited the
      severity of the stroke but warfarin therapy would not likely have reached
      therapeutic levels within 2days. CONCLUSION: The preventive effect of warfarin on
      early stroke associated with new atrial fibrillation after CABG seems limited.
      Treatment with warfarin during the hospitalization has to take the risk of
      bleeding, particularly into the pericardium, as reported in the literature, into
      account.

PMID- 25776469
TI  - Aspirin resistance in children and young adults with splenectomized thalassemia
      diseases.
AB  - Aspirin is now recommended for splenectomized thalassemia patients with high
      platelet counts. However, aspirin resistance defined by arachinodic acid (ACA)
      induced platelet aggregation >=20%, has never been reported in this group of
      patients. In this study, twenty-four splenectomized thalassemia patients (15.7+/
      4.1years), with platelet counts >=800x10(9)/L, and 21 non-splenectomized severe
      thalassemia patients (14.3+/-3.2years), were enrolled. After taking aspirin
      (2mg/kg/day), seven patients (29.2%) displayed aspirin resistance. Serum
      thromboxane B2 (TXB2) levels in the aspirin responsive group decreased
      significantly [52.6(8.8-174.6) vs 4.0(1.6-7.3) mcg/mL, p<0.001], while no change
      was demonstrated in the aspirin resistant group. Having increased aspirin to
      4mg/kg/day, three of the seven aspirin resistant patients responded, while one
      developed upper GI bleeding from esophageal varices and was withdrawn from the
      study. For the three remaining patients, their doses were increased to the
      maximum of 300mg/day, and two of the three responded. Thrombin antithrombin
      complex and D-dimer levels were significantly decreased after taking aspirin
      (2mg/kg/day), although D-dimer level was still significantly higher than that in
      non-splenectomized group. Therefore, aspirin dosage can be adjusted individually
      to reach maximum effect of platelet inhibition. In addition, aspirin can reduce
      the levels of coagulation markers. 

PMID- 25776470
TI  - N-acetylcysteine relieves oxidative stress and protects hippocampus of rat from
      radiation-induced apoptosis by inhibiting caspase-3.
AB  - It has been recognized that radiation-induced effects remain a significant risk.
      An accumulation of reactive oxygen species (ROS) is considered to be one factor
      that contributes to neurodegenerative changes. The aim of our study was to
      investigate the potential radioprotective effects of NAC. Male Sprague-Dawley
      rats underwent radiation. Irradiation was performed at room temperature with a 4
      Gy dose of radiation. A dose of N-acetylcysteine (NAC) was performed 15 min prior
      to irradiation intraperitoneally. The methods of immunohistochemistry, TUNEL
      staining, Nissl staining, qRT-PCR, analysis of reactive oxygen species and
      Western blot were performed. In conclusion, our results demonstrate that NAC
      inhibits apoptosis induced by irradiation via the inhibition of caspase-3. We
      demonstrated a decrease in caspase-3 mRNA that was present at 24h of NAC
      treatment. Such mRNA decrease was accompanied by a decrease of protein. In the
      present study, NAC effectively antagonized oxidation induced by irradiation.
      These results provide evidence that the neural protective effect and the
      antioxidant effect of NAC contribute to metabolic activity.

PMID- 25776471
TI  - PPARD rs2016520 polymorphism and circulating lipid levels connect with brain
      diseases in Han Chinese and suggest sex-dependent effects.
AB  - The PPARD polymorphisms were shown to be associated with circulating lipoprotein
      metabolism in various diseases. We aimed to check the contribution of PPARD
      rs2016520 and lipid concentration to the risk of intracerebral hemorrhages (ICH)
      and brain tumors (BT) in Han Chinese. A total of 864 participants were included
      in the case-control study. The melting temperature shift (Tm-shift) method was
      used for rs2016520 genotyping. Under the recessive model, PPARD rs2016520 was
      shown to be associated with the risk of ICH (P=0.029, odds ratio (OR)=2.72),
      specifically in males (P=0.045, OR=3.98). Additionally, we also found that the
      levels of TC and LDL-C were significantly higher in participants with brain
      diseases than in the controls (TC: P<0.0001; LDL-C: P<0.0001). Significantly
      higher HDL-C and lower ApoA-I levels were observed in the male patients with
      brain diseases (HDL-C: P<0.0001; ApoA-I: P=0.008), in contrast of a higher TG
      level in female ICH (P=0.023). Subsequent interaction analysis between PPARD
      rs2016520 and lipoprotein metabolism showed that the LDL-C level was positively
      correlated with ICH in the rs2016520-AA carriers (P<0.0001), but not in the other
      genotype carriers (AG or GG, P=0.300). Our results showed that PPARD rs2016520
      displayed a strong relationship with ICH risk in the male Han Chinese. The TC and
      LDL-C levels were positively higher in the patients with brain diseases than in
      the controls. The levels of TG, HDL-C and ApoA-I were shown to affect brain
      disease in a gender-dependent model. The genotype rs2016520-AA showed significant
      interaction with the circulating LDL-C levels in ICH. 

PMID- 25776472
TI  - Immunomodulatory action of Copaifera spp oleoresins on cytokine production by
      human monocytes.
AB  - Copaifera spp oleoresins have been used in folk medicine for centuries;
      nevertheless, its immunomodulatory action has not been investigated. Thus, the
      goal of this study was to characterize different oleoresins and to verify their
      action on human monocytes regarding pro- and anti-inflammatory cytokine
      production (TNF-alpha and IL-10, respectively). The chemical composition of
      Brazilian Copaifera reticulata, Copaifera duckey and Copaifera multijuga
      oleoresins was analyzed by HPLC-MS. Cell viability was assessed by MTT method
      after incubation of cells with Copaifera spp. Noncytotoxic concentrations of
      oleoresins were incubated with human monocytes from healthy donors, and cytokine
      production was determined by ELISA. HPLC-MS analysis for terpenes allowed the
      identification of six diterpene acids and one sesquiterpene acid. Oleoresins
      exerted no cytotoxic effects on human monocytes. All oleoresins had a similar
      profile: LPS-induced TNF-alpha production was maintained by oleoresins, while a
      significant inhibitory action on IL-10 production was seen. Copaifera oleoresins
      seemed to exert an activator profile on human monocytes without affecting cell
      viability. Such effect may be due to the presence of either diterpene or
      sesquiterpene acids; however, further studies are necessary to determine the
      involvement of such compounds in Copaifera immunomodulatory effects. 

PMID- 25776473
TI  - Clinical significance of serum interleukin-18 (IL-18) levels in patients with
      gastric cancer.
AB  - An inappropriate production of interleukin-18 (IL-18) contributes to the
      pathogenesis of malignancies and may influence the clinical outcome of patients.
      The objective of this study was to determine the clinical significance of the
      serum levels of IL-18 in patients with gastric cancer. A total of 63 patients
      with a pathologically confirmed diagnosis of gastric cancer were enrolled into
      this study. Serum IL-18 concentrations were determined by the solid-phase
      sandwich Elisa method. Age- and sex-matched 30 healthy controls were included in
      the analysis. The median age at diagnosis was 62 years, range 28 to 82 years. The
      baseline serum IL-18 levels of the gastric cancer patients were a significantly
      higher than those in the control group (median values 1436.4 vs. 638.4 pg/mL,
      respectively, P<0.001). The known clinical variables including age of patient,
      gender, site of lesion, histology, histological grade, stage of disease, and
      serum tumor markers such as LDH, CEA, and CA 19.9 were not found to be correlated
      with serum IL-18 concentrations (P>0.05). Moreover, no correlation was found
      between serum IL-18 level and response to chemotherapy (P=0.34). Serum IL-18
      concentration was also found no prognostic role on survival (P=0.21). In
      conclusion, serum levels of IL-18 may have a good diagnostic marker in patients
      with gastric cancer. However, its predictive and prognostic values were not
      determined.

PMID- 25776474
TI  - Expression of 17beta-hydroxysteroid dehydrogenase type 2 is associated with some
      clinicopathological features in gastric cancer.
AB  - In most populations, gastric cancer (GC) incidence is higher in men than in
      women, which may suggest the role of sex steroid hormones in gastric
      cancerogenesis. Both, androgens and estrogens can be synthetised in peripherial
      tissues. This process is controlled by expression of steroidogenic enzymes.
      Therefore, we evaluate the 17beta-hydroxysteroid dehydrogenase type 2 (HSD17B2)
      transcript and protein levels in gastric tumoral and nontumoral tissue. We also
      determined the association between HSD17B2 transcript and protein levels and some
      clinicopathological features in GC. We found significantly decreased levels of
      HSD17B2 transcript (P=0.00072) and protein (P=0.00017) in primary tumoral tissues
      of GC patients, as compared to nontumoral tissues. In patients above 60 years of
      age the amounts of HSD17B2 transcript (P=0.00044) and protein (P=0.00027) were
      significantly lower in tumoral than nontumoral tissues. Similarly, lower HSD17B2
      levels, both in terms of the transcript and protein, were observed in tumoral
      tissues of male (P=0.013, P=0.0014), patients stomach (P=0.0062, P=0.045) and
      cardia (P=0.02, P=0.02) site of tumor, T3 (P=0.018, P=0.014) depth of invasion,
      N0 (P=0.017, P=0.045) lymph node metastasis, G3 (P=0.0027, P=0.014) malignancy
      grade. We also observed significantly reduced level of HSD17B2 transcript in
      tumoral tissue specimens of females (P=0.014), T4 depth of invasion (P=0.02), N3
      lymph node metastasis (P=0.037) and G2 malignancy grade (P=0.045). Furthermore,
      diffuse GC histological types were associated with lower HSD17B2 protein level
      (P=0.024) than nontumoral tissues. We demonstrated that HSD17B2 transcript and
      protein levels are linked to some clinicopathological features in GC.

PMID- 25776475
TI  - Functional promoter rs2295080 T>G variant in MTOR gene is associated with risk of
      colorectal cancer in a Chinese population.
AB  - BACKGROUND: The mammalian target of rapamycin (mTOR) plays an important role in
      the development and progression of colorectal cancer (CRC). Recently, a
      functional polymorphism (rs2295080 T>G) in the promoter of MTOR has been shown to
      influence its expression and confer susceptibility to cancer. Therefore, in the
      present study, we sought to investigate the influence of this polymorphism on the
      risk of CRC. METHODS: We genotyped this polymorphism by using the TaqMan method
      in a case-control study comprising of 737 CRC patients and 777 controls. The
      logistic regression was used to assess the genetic association with occurrence of
      CRC. The functionality of the polymorphism was examined by luciferase reporter
      assay. RESULTS: We found the variant genotypes of MTOR rs2295080 (TG/GG) were
      significantly associated with decreased CRC risk, compared with the wild genotype
      [TG/GG vs. TT: adjusted odds ratio (OR)=0.76, 95% confidence interval (CI)=0.62
      0.94, P=0.011], and the protective effect of this polymorphism was more
      predominant among the subgroups of elder (OR=0.66, 95% CI=0.49-0.89) and male
      (OR=0.63, 95% CI=0.48-0.84) subjects. Furthermore, the luciferase reporter assay
      showed that the rs2295080G allele significantly decreased the luciferase activity
      in both sw480 and sw620 cell lines (P=0.002 and P<0.001, respectively).
      CONCLUSIONS: Our results suggest that the functional rs2295080 T>G in the
      promoter of MTOR may influence the susceptibility of CRC in the Chinese
      population through regulating the transcription activity of MTOR promoter. Large
      population-based prospective studies are required to validate our findings.

PMID- 25776476
TI  - Cytotoxic activity of sunitinib and everolimus in Caki-1 renal cancer cells is
      accompanied by modulations in the expression of apoptosis-related microRNA
      clusters and BCL2 family genes.
AB  - Sunitinib and everolimus are two of the antineoplastic agents indicated for the
      management of metastatic renal cancer. Although both of the above compounds were
      primarily designed as antiangiogenic factors, preclinical studies claim that
      these drugs can also trigger apoptosis. Herein, we sought to evaluate the
      cytotoxic activity of sunitinib and everolimus against renal cancer cells Caki-1
      and moreover to assess their impact on the expression levels of three BCL2 family
      members and three apoptosis-related microRNA clusters upon incubation with the
      drugs or following recovery from treatment. The cytotoxic effect of sunitinib and
      everolimus on Caki-1 cells' viability was estimated by the MTT assay, while
      cleaved PARP, assayed via Western Blotting, served as a marker of programmed cell
      death. As for the expression levels of the BCL2 family members BCL2, BAX and
      BCL2L12 and those of the mature microRNAs of the miR-183/96/182, miR-143/145, and
      miR-15a/16 clusters, they were quantified via real-time PCR. Our results showed
      that both agents induced a time- and dose-dependent decrease in cell viability
      and promoted cleavage of PARP. In parallel, significant modulations were observed
      in the expression levels of miR-145, miR-15a, and miR-16 in case of sunitinib,
      whereas BCL2, BAX, miR-145 and miR-15a expression was strongly affected by
      everolimus. Overall, our data support the notion that sunitinib and everolimus
      are able to directly induce cell death in renal cancer cells and simultaneously
      affect the expression levels of their apoptosis-related microRNAs and BCL2 family
      members upon this process. 

PMID- 25776477
TI  - The tetravalent anti-DR5 antibody without cross-linking direct induces apoptosis
      of cancer cells.
AB  - Tumor necrosis factor-related apoptosis-inducing ligand can induce apoptosis in
      many tumor cell lines. This apoptotic effect is mediated by interaction of TRAIL
      and its receptors, which include Death Receptor 4 (DR4) and Death Receptor 5
      (DR5). Some antibodies to DR4 or DR5 do not have anti-tumor ability without cross
      linking but exhibit anti-tumor ability in the presence of a cross-linking
      reagent. Here, we suggest that the tetravalent anti-DR5 antibody can induce
      apoptosis of cancer cells independent of cross-linking reagent. The single-chain
      variable fragment of the anti-DR5 antibody, HSA (human serum albumin) - p53 gene,
      comprising residues 490-513 of HSA and the tetramerization domain of human p53
      were assembled into the tetravalent antibody by an overlapping PCR. Results of
      size exclusion HPLC indicated that the purified protein exhibited a major peak
      (tetramer) and a minor peak (dimer). MTT assay demonstrated the tetravalent
      antibody without cross-linking could inhibit survival of Jurkat and EC9706 cells
      in a dose-dependent manner while the monovalent antibody could not inhibit
      survival of Jurkat and EC9706 cells. IC50 of Jurkat cell was 3.2 mg/L and IC50 of
      EC9706 cell was 3.9 mg/L. Furthermore, the Annexin V/PI assay and the Hoechst
      33258 staining showed that the tetravalent antibody could efficiently induce
      apoptosis of Jurkat and EC9706 cells. Therefore, the tetravalent anti-DR5
      antibody can act as a direct agonistic antibody, and initiate efficient apoptotic
      independent of cross-linking reagent. Thus, the tetravalent anti-DR5 antibody
      will be a new kind of candidate for potential cancer therapeutics. 

PMID- 25776478
TI  - Didanosine-loaded chitosan microspheres optimized by surface-response
      methodology: a modified "Maximum Likelihood Classification" approach formulation
      for reverse transcriptase inhibitors.
AB  - Didanosine-loaded chitosan microspheres were developed applying a surface
      response methodology and using a modified Maximum Likelihood Classification. The
      operational conditions were optimized with the aim of maintaining the active form
      of didanosine (ddI), which is sensitive to acid pH, and to develop a modified and
      mucoadhesive formulation. The loading of the drug within the chitosan
      microspheres was carried out by ionotropic gelation technique with sodium
      tripolyphosphate (TPP) as cross-linking agent and magnesium hydroxide (Mg(OH)2)
      to assure the stability of ddI. The optimization conditions were set using a
      surface-response methodology and applying the "Maximum Likelihood
      Classification", where the initial chitosan concentration, TPP and ddI
      concentration were set as the independent variables. The maximum ddI-loaded in
      microspheres (i.e. 1433 mg of ddI/g chitosan), was obtained with 2% (w/v)
      chitosan and 10% TPP. The microspheres depicted an average diameter of 11.42 MUm
      and ddI was gradually released during 2 h in simulated enteric fluid.

PMID- 25776479
TI  - Characterization of effector components from the humoral and cellular immune
      response stimulated by melanoma cells exhibiting modified IGF-1 expression.
AB  - Modified melanoma B16 cells inhibited in their IGF-1 expression (B16MOD), on the
      contrary to the IGF-1 fully expressed parental wild-type (B16WT) counterpart,
      were shown to stimulate humoral as well as cellular immune responses. Among
      humoral components, the neutralizing and complement-fixing antibodies of IgM and
      essentially IgG2 (a+b) isotypes exhibited in vitro and in vivo effects upon
      tumour growth, while the IgG1 antibody isotype promoted enhanced tumour
      proliferation. As for the cellular immunity, it was found that the T CD8(+)
      lymphocyte subpopulation remained the main potent and long lasting immune active
      effector regulating tumour growth. 

PMID- 25776480
TI  - Annexin A11 knockdown inhibits in vitro proliferation and enhances survival of
      Hca-F cell via Akt2/FoxO1 pathway and MMP-9 expression.
AB  - Annexin A11 (Anxa11), a Ca(2+)-regulated phospholipid-binding protein, is
      involved in cell apoptosis, differentiation, vesicle trafficking, cancer
      progression and autoimmune diseases. Previous study from our group indicated that
      Anxa11 was associated with lymphatic metastatic potential of murine
      hepatocarcinoma cells. Herein, we investigated the effects and action mechanism
      of Anxa11 knockdown on in vitro cell proliferation and apoptosis of Hca-F, a
      murine hepatocarcinoma cell with~75% lymph node metastatic potential. Real-time
      PCR and western blotting assays indicated that Anxa11 was significantly
      downregulated in monoclonal Anxa11-shRNA-transfected Hca-F cells. Anxa11
      knockdown in Hca-F suppressed its in vitro proliferation and cell apoptosis
      capacities. Following Anxa11 knockdown in Hca-F cells, Bax/Bcl-2 expression level
      ratio, Akt2 and FoxO1 (pSer319) expression levels as well as MMP-9 mRNA and
      active MMP-9 protein levels were significantly elevated in Hca-F cells. In
      conclusion, Annexin A11 knockdown inhibits the in vitro proliferation and cell
      apoptosis of Hca-F cell via Akt2/FoxO1 and/or MMP-9 expression pathway. Anxa11
      might play an important role in hepatocarcinoma cell invasion and metastasis and
      hepatocarcinoma malignancy. 

PMID- 25776481
TI  - miR-377 functions as a tumor suppressor in human clear cell renal cell carcinoma
      by targeting ETS1.
AB  - Clear cell renal cell carcinoma (ccRCC) is the most common form of neoplasm
      occurring in the adult kidney. Although significant advances have been made in
      treatment for ccRCC, a significant percent of patients have no benefit from
      currently available treatment option. MicroRNAs (miRNAs) have been reported to
      play central roles in regulating tumor progression, and are being explored as
      potentially more effective therapies and diagnostic tools for various cancers.
      The transcription factor E26 transformation specific-1 (ETS1) is believed to be
      intimately involved in tumor progression, and is frequently upregulated in
      tumors, including ccRCC. However, few studies have investigated the implications
      of ETS1 in ccRCC, and no studies have investigated the dysregulated mechanisms
      responsible for aberrant ETS1 expression in ccRCC. We used databases, clinical
      samples and target prediction algorithms to investigate aberrant miR-377
      expression and potential targets in ccRCC. Our results indicate that miR-377 is
      downregulated in ccRCC, and that miR-377 can regulate the expression of ETS1.
      Further, using cell cycle analysis, MTT, luciferase and knockdown experiments, we
      found evidence to suggest that ETS1 is central in the development of the
      proliferative, metastatic and invasive phenotype of ccRCC cells. Furthermore, miR
      377 was found to directly downregulate the expression of ETS1 and reduce the
      ability of ccRCC cells to proliferate, migrate and invade. As miR-377 was found
      to be differentially expressed in ccRCC, and in light of the apparent central
      role of ETS1 in tumor development, our results indicate that miR-377 could be
      useful for ccRCC diagnostics, prognostics and therapeutics. 

PMID- 25776482
TI  - Expression of MicroRNA-325-3p and its potential functions by targeting HMGB1 in
      non-small cell lung cancer.
AB  - MicroRNAs (miRNAs) can function as tumor suppressors and might provide an
      efficient strategy for annihilating cancer. Nevertheless, the potential role of
      miR-325-3p in NSCLC is still unknown. Here, we showed that miR-325-3p was
      decreased and HMGB1 was increased in 107 NSCLC patients. MiR-325-3p inhibition
      promoted cell invasion and proliferation, while miR-325-3p upregulation inhibited
      cell invasion and proliferation by using transwell and CCK8 assays. Using a
      bioinformatics method, we further showed that HMGB1 might be a direct target of
      miR-325-3p and is negatively regulated by miR-325-3p. Down-regulation of miR-325
      3p predicts poor prognosis for NSCLC patients. These findings implied that miR
      325-3p regulates cell invasion and proliferation via targeting HMGB1 and may be a
      potential prognostic marker for NSCLC. 

PMID- 25776483
TI  - Association of four CpG-SNPs in the vascular-related genes with coronary heart
      disease.
AB  - Vascular-related gene polymorphism can affect the susceptibility of coronary
      heart disease. In current study, we aimed to evaluate the contribution of four
      vascular-related gene CpG-SNPs to coronary heart disease (CHD). A total of 784
      angiography-proven CHD patients and 746 non-CHD controls were included in the
      current association study. The four CpG-SNPs (including VEGFA rs1005230, ACE
      rs4316, CST3 rs3827143 and AGTR1 rs275653) were genotyped using the Sequenom
      MassARRAY platform. All genotype distribution of four SNPs met HWE. Among the
      four CpG-SNPs, none was found to be associated with CHD on both genotype and
      allele levels. Further subgroup tests by age or gender were unable to observe any
      significant associations of them with CHD. Our case-control study showed that
      none of four CpG-SNPs in the vascular-related genes was associated with the risk
      of CHD in Han Chinese, although we could not exclude other genetic variants of
      these vascular-related genes with contribution to CHD. 

PMID- 25776484
TI  - Dub3 expression correlates with tumor progression and poor prognosis in human
      epithelial ovarian cancer.
AB  - Dub3 is a deubiquitinating enzyme. It is highly expressed in tumor-derived cell
      lines and has an established role in tumor proliferation. However, the role of
      Dub3 in human ovarian cancer remains unclear. Expression of Dub3 was evaluated in
      ovarian cancer tissues and cell lines by immunohistochemistry and Western blot
      analysis. The relationship between Dub3 expression and clinicopathological
      characteristics was analyzed. Using RNA interference, the effects of Dub3 on cell
      proliferation and apoptosis were investigated in ovarian cancer cell line. All
      normal ovary tissues exhibited very little or no Dub3 immunoreactivity. High
      levels of Dub3 expression were examined by immunohistochemical analysis in 13.3%
      of cystadenomas, in 30.0% of borderline tumors, and in 58.9% of ovarian
      carcinomas, respectively. Dub3 expression was significantly associated with lymph
      node metastasis and clinical staging (P<0.05). Multivariate survival analysis
      indicated that Dub3 expression was an independent prognostic indicator of the
      survival of patients with ovarian cancer. Furthermore, the expression of Cdc25A
      was closely correlated with that of Dub3 in cancer cells and tissues. Knockdown
      of Dub3 could inhibit the proliferation of ovarian cancer cells and increase cell
      apoptosis. These data indicate that the Dub3 might be a valuable biomarker for
      the prediction of ovarian cancer prognosis and Dub3 inhibition might be a
      potential strategy for ovarian cancer treatment. 

PMID- 25776485
TI  - ATPase inhibitory factor 1 is a prognostic marker and contributes to
      proliferation and invasion of human gastric cancer cells.
AB  - ATPase inhibitory factor 1 (IF1) has recently been considered as a potential
      oncogene in human cancers. Recently, increasing evidences have shown that IF1 is
      overexpressed in human cancers and promotes tumor growth and metastasis. In this
      study, we found that the expression levels of IF1 protein and mRNA in gastric
      cancer tissues were significantly higher than those in matched adjacent nontumor
      tissues. Clinical association analysis revealed that the positive expression of
      IF1 was correlated with large tumor size, lymph node metastasis, venous
      infiltration and advanced TNM tumor stage in gastric cancer. Furthermore, IF1 was
      an independent prognostic marker for predicting 5-year overall survival and
      disease-free survival of gastric cancer patients. In vitro studies found that IF1
      knockdown significantly inhibited cell proliferation and induced apoptosis in SGC
      7901 cells. In a nude mouse xenograft model, IF1 knockdown prominently slowed
      down tumor growth with reduced number of Ki-67 positive cancer cells and elevated
      number of TUNEL positive cancer cells. Otherwise, IF1 knockdown evidently reduced
      SGC-7901 cell migration and invasion. In conclusion, these results indicate that
      IF1 may serve as a prognostic marker and promotes tumor growth and metastasis in
      gastric cancer. 

PMID- 25776487
TI  - Overview of high-risk HPV's 16 and 18 infected cervical cancer: pathogenesis to
      prevention.
AB  - As general, the Human papillomavirus (HPV) causes the most sexually transmitted
      diseases. Among well categorized 80 types, the high-risk types HPV's 16 and 18
      are highly involved in 70% of cervical cancer. The virulence of HPV is mainly
      exhibited by E5, E6 and E7 encoded oncoproteins that cause low to high-grade
      cervical lesions (CIN-1, 2, 3), leading to form 99.7% of squamous cell and 89% of
      adenocarcinomas cervical cancer worldwide. This study mainly encircles the major
      role of E5, E6 and E7 oncoproteins in HPV 16 and 18. Further discussed the
      uprising of significant biomarkers and their cellular process in different stages
      of cervical cancer with current prevention and treatment regimens. Hence, this
      integration will evoke novel markers, potential vaccination and various
      treatments approaches with special reference for HPV16 and 18 infected cervical
      cancers. 

PMID- 25776486
TI  - HtrA1 resensitizes multidrug-resistant hepatocellular carcinoma cells by
      targeting XIAP.
AB  - The study aims to clarify the relation between chemosensitivity and HtrA1
      expression, and the possible way HtrA1 works. Drug-resistant cell line HepG2/ADM
      was induced by increasing adriamycin (ADM), and eukaryotic expression vector
      pEGFP-N1-HtrA1 was constructed using BamHI and EcoRI restriction enzymes, after
      which, HepG2/ADM was transfected with pEGFP-N1-HtrA1. Resistance index (RI) of
      the hepatoma cell lines to different anti-cancer drugs (ADM, 5-Fu, MMC, L-OHP and
      VCR) was determined by MTT assay before and after HtrA1 high expression. After an
      HtrA1 inhibitor, NVP-LEB748 was adopted in the HtrA1 overexpressing cells,
      expression of proteins P-gp, MRP and XIAP (X-linked inhibitor of apoptosis
      protein) in HepG2/ADM cells were analyzed by western blot, and the activities of
      caspases 3, 7 and 9 were respectively measured using activity assay kits. The
      results showed that RI was negatively correlated with the expression of HtrA1,
      upregulated XIAP expression was resulted from the HtrA1 inhibitor, and variance
      of activities of caspases 3, 7 and 9 were remarkably descended with its
      increasing concentration. It was concluded that high expression of HtrA1 could
      significantly reverse multidrug resistance of hepatoma cells by targeting XIAP.
      HtrA1 is therefore expected to be an effective tool in the therapy of
      hepatocellular carcinoma. 

PMID- 25776488
TI  - Podophyllotoxin acetate enhances gamma-ionizing radiation-induced apoptotic cell
      death by stimulating the ROS/p38/caspase pathway.
AB  - To develop a new radiosensitizer against non-small cell lung cancer cells, we
      screened a natural product library for growth-inhibitory compounds. PA was found
      to be cytotoxic toward NCI-H460 cells, and its IC50 value was determined. The
      radiosensitizer effects of PA were tested at its IC50 value in clonogenic and
      cell-counting assays. The intracellular mechanism underlying this effect was
      determined by immunoblotting and by measuring propidium iodide uptake and ROS
      generation. The radiosensitizer activity of PA in vivo was tested in nude mice by
      treating with PA and IR, and measuring tumor volume and assessing apoptosis. PA,
      tested at its experimentally determined IC50 value (12 nM), enhanced IR-induced
      death of NCI-H460 cells by increasing apoptosis, yielding a mean calculated dose
      enhancement ratio of 1.67. Combination with PA and IR also increased the
      production of ROS, which subsequently induced phosphorylation of p38, suppressed
      phosphorylation of ERK, and activated caspase-3, -8, and -9. Notably, inhibition
      of ROS production prevented p38 phosphorylation, and inhibition of ROS production
      or p38 activation blocked caspase activation and apoptosis. In a xenograft assay,
      combination with PA and IR delayed tumor growth by 11.4 days compared with
      controls, yielding an enhancement factor of 1.48. Collectively, these results
      indicate that PA functions as a radiosensitizer by enhancing apoptosis through
      activation of a ROS/p38/caspase pathway and suppression of ERK.

PMID- 25776489
TI  - Is the pharmacokinetics of bupivacaine equivalent after lumbar epidural
      administration through a needle or a catheter in male and female adults?
AB  - We assessed possible pharmacokinetic modifications due to different epidural
      injection techniques using either a needle or a catheter. Adult patients (n=23)
      undergoing lower abdominal or lower extremity surgery were randomly assigned a
      single bupivacaine epidural injection anesthesia (0.5%, 15 mL, 0.3 mL/s) through
      needle or catheter device. Plasma bupivacaine concentration was quantified using
      a validated HPLC method and non-compartmental pharmacokinetic parameters
      estimated. CMAX and TMAX were similar in both groups: 952 +/- 346 ng/mL, 0.65 +/-
      0.5 1h in the needle group; 810 +/- 307 ng/mL, 0.43 +/- 0.29 h in the catheter
      group respectively. Plasma AUC0->infinity was also similar in both groups: 3868
      +/- 1687 ngh/mL for needle versus 4096 +/- 1748 ngh/mL using catheter. The
      catheter group showed slower disposition than the needle group: t1/2=3.9 +/- 2.3
      h, MRT=6.0 +/- 3.1 h versus 2.7 +/- 1.03 h and 4.5 +/- 1.2 h with needle
      administration respectively though it did not reach statistical significance,
      Cl/F and V/F were also similar. Lastly, female patients showed significant longer
      t1/2 after administration through catheter (5.7 +/- 2.0 h) than needle (2.7 +/-
      0.6 h) group (P=0.0279). The device type does not affect the pharmacokinetics
      which is similar in both groups although sex-based differences might exist.

PMID- 25776490
TI  - Molecularly targeted gemcitabine-loaded nanoparticulate system towards the
      treatment of EGFR overexpressing lung cancer.
AB  - Molecularly targeted therapy emerged as a novel therapeutic strategy in the
      treatment of multiple cancers. In the present study, we have developed
      gemcitabine (GEM)-loaded cetuximab (CET) surface modified poly(lactic) acid (PLA)
      nanoparticles (NP) (CET-GEM/PLA NP) to target to epidermal growth factor receptor
      (EGFR) overexpressing non-small cell lung cancer (A549) cells. The resultant CET
      GEM/PLA NP showed a very uniform particle size of~120 nm and spherical
      morphology. It exhibited a pH-dependent controlled release pattern. A sustained
      release of drug in the physiological conditions and faster release in tumor pH
      will greatly improve the chemotherapeutic efficiency of therapeutic system.
      Higher or enhanced cellular uptake of CET-GEM/PLA NP in A549 cancer cells clearly
      indicates the EGFR-mediated receptor based active targeting. Nearly, a two-fold
      increase in fluorescent intensity was observed for CET-GEM/PLA NP comparing to
      that of non-targeted NP in the cancer cells. EGFR-mediated internalization of the
      targeted NP was further confirmed by the confocal microscopy. MTT assay clearly
      showed the enhanced cell killing effect of CET-conjugated NP due to the selective
      delivery of GEM to the EGFR over expressing cancer cells. Finally, comparing to
      the non-targeted NP, CET-GEM/PLA NP showed greater level of cell apoptosis (early
      and late apoptosis~40%). Our results showed that antibody conjugation on the
      surface of NP could be a potential treatment strategy for EGFR over expressing
      cancer cells. This suggests that CET-GEM/PLA NP could be potentially used for the
      treatment of NSCLC (lung cancers).

PMID- 25776491
TI  - Toluhydroquinone, the secondary metabolite of marine algae symbiotic
      microorganism, inhibits angiogenesis in HUVECs.
AB  - Angiogenesis, the growth of new blood vessels from the existing ones, occurs
      during embryo development and wound healing. However, most malignant tumors
      require angiogenesis for their growth and metastasis as well. Therefore,
      inhibition of angiogenesis has been focused as a new strategy of cancer
      therapies. To treat cancer, there are marine microorganism-derived secondary
      metabolites developed as chemotherapeutic agents. In this study, we used
      toluhydroquinone (2-methyl-1,4-hydroquinone), one of the secondary metabolites
      isolated from marine algae symbiotic fungus, Aspergillus sp. We examined the
      effects of toluhydroquinone on angiogenesis using HUVECs. We identified that
      toluhydroquinone inhibited the activity of beta-catenin and down-regulated
      Ras/Raf/MEK/ERK signaling which are crucial components during angiogenesis. In
      addition, the expression and activity of MMPs are reduced by the treatment of
      toluhydroquinone. In conclusion, we confirmed that toluhydroquinone has
      inhibitory effects on angiogenic behaviors of human endothelial cells, HUVECs.
      Our findings suggest that toluhydroquinone can be proposed as a potent anti
      angiogenesis drug candidate to treat cancers. 

PMID- 25776492
TI  - Effects of natural nuclear factor-kappa B inhibitors on anticancer drug efflux
      transporter human P-glycoprotein.
AB  - Drug efflux transporter P-glycoprotein plays an important role in cancer
      chemotherapy. The nuclear factor-kappaB (NF-kappaB) transcription factors play
      critical roles in development and progression of cancer. In this study, the
      effects of natural compounds that can inhibit NF-kappaB activation on the
      function of P-glycoprotein were investigated using human MDR1 gene-transfected
      KB/MDR1 cells. The accumulation of daunorubicin or rhodamine 123, fluorescent
      substrates of P-glycoprotein, in KB/MDR1 cells increased in the presence of
      caffeic acid phenetyl ester (CAPE), licochalcone A, anacardic acid, celastrol,
      xanthohumol, magnolol, and honokiol in a concentration-dependent manner. In
      contrast, lupeol, zerumbone, thymoquinone, emodin, and anethol had no effects.
      The ATPase activities of P-glycoprotein were stimulated by CAPE, licochalcone A,
      anacardic acid, celastrol, xanthohumol, magnolol, and honokiol. Tumor necrosis
      factor (TNF)-alpha stimulated NF-kappaB activation was inhibited by CAPE,
      licochalcone A, anacardic acid, and xanthohumol. KB/MDR1 cells were sensitized to
      vinblastine cytotoxicity by CAPE, licochalcone A, anacardic acid, xanthohumol,
      magnolol, and honokiol, showing that these natural NF-kappaB inhibitors reverse
      multidrug resistance. These results suggest that natural compounds, such as CAPE,
      licochalcone A, and anacardic acid, have dual inhibitory effects on the
      anticancer drug efflux transporter P-glycoprotein and NF-kappaB activation, and
      may become useful to enhance the efficacy of cancer chemotherapy. 

PMID- 25776493
TI  - Down-regulated expression of Annexin A7 induces apoptosis in mouse
      hepatocarcinoma cell line by the intrinsic mitochondrial pathway.
AB  - Our previous studies have shown that decreased expression of Annexin A7 elevates
      apoptosis in Hca-P cells, a hepatocarcinoma cell line with lymphatic metastatic
      potential. In this study, RNA interference technique was used to down-regulate
      the expression of Annexin A7, and unmanipulated Hca-P cells and transfected
      nonspecific-sequence Hca-P cells as control. The down-regulation of Annexin A7
      declined the cell viability after cisplatin exposure. And the reduced expression
      of Annexin A7 decreased the expression of Bcl2, increased the expression of
      Cytochrome-C in the cytoplasme, and then improved the expression of Caspase-3.
      However there was no significant effect on the expression of Bax, Caspase-12,
      Fas, FasL and Caspase-8. The results indicate that the decreased expression of
      Annexin A7 could inhibit the proliferation, and increase the apoptosis of Hca-P
      cells by affecting the expression of the apoptosis associated proteins by the
      mitochondrial pathway. 

PMID- 25776494
TI  - miR-183 induces cell proliferation, migration, and invasion by regulating PDCD4
      expression in the SW1990 pancreatic cancer cell line.
AB  - The aim of this study was to investigate the function of miR-183 in the SW1990
      cancer cell line, and the mechanisms regulating these processes. miRNAs are known
      to play important roles in cancer cell development. However, the pattern and
      biological role of miR-183 in pancreatic cancer remain largely unknown. Here, we
      have reported the reduction in pancreatic cancer cell growth in vitro by miR-183
      intervention, by inducing apoptosis and decreasing the Bcl-2 expression.
      Moreover, miR-183 was observed to enhance pancreatic cancer cell migration and
      invasion, whereas inhibition of miR-183 caused an opposite effect. miR-183
      inhibition was shown to increase E-cadherin expression and decrease N-cadherin
      expression. These regulatory actions play an important role in the cancer
      epithelial-mesenchymal transition (EMT). Mechanistically, we demonstrated that
      the overexpression of miR-183 decreased the expression of PDCD4 (programmed cell
      death 4) mRNA and protein, and vice versa. This helped to identify PDCD4 as the
      target genes in pancreatic cancer. In conclusion, our analyses indicated miR-183
      to be an important contributor to cell migration. This could also be used as a
      potential therapeutic target for pancreatic cancer treatment. 

PMID- 25776495
TI  - miR-411 regulated ITCH expression and promoted cell proliferation in human
      hepatocellular carcinoma cells.
AB  - Hepatocellular carcinoma (HCC) is one of the most common human malignancies and
      the third most common cause of cancer mortality in the world. In this study, we
      report that miR-411 expression is markedly upregulated in HCC cells and HCC
      tissues compared with normal control tissues and cells. Previous studies have
      shown that miR-411 plays a crucial role in a variety of biological processes in
      various human cancer cells. However, the specific function of miR-411 in HCC
      remains unclear. Ectopic expression of miR-411 promoted the proliferation and
      anchorage-independent growth of HCC cells, whereas inhibition of miR-411 reduced
      this effect. Bioinformatics analysis further revealed ITCH, a putative tumor
      suppressor as a potential target of miR-411. Data from luciferase reporter assays
      showed that miR-411 directly binds to the 3'-untranslated region (3'-UTR) of ITCH
      mRNA and repressed expression at both transcriptional and translational levels.
      In functional assays, miR-411 promoted HCC cell proliferation, which could be
      suppressed by miR-411-in. Taken together, our data provide convincing evidence
      that miR-411 functions as an onco-miRNA, which was associated with cell
      proliferation of HCC, and its oncogenic effect is mediated chiefly through direct
      suppression of ITCH expression. 

PMID- 25776496
TI  - MiR-522 contributes to cell proliferation of human glioblastoma cells by
      suppressing PHLPP1 expression.
AB  - Previous studies have shown that microRNAs play essential roles in cancer growth
      and progression. Although a number of microRNAs were differentially expressed in
      glioblastoma (GBM). In this study, we evaluated the miR-522s role in cell
      proliferation in GBM. Expression of miR-522 is markedly upregulated in GBM
      tissues and GBM cells compared with the matched non-tumor adjacent brain tissues
      (TAT) and normal human astrocytes (NHAs). In functional assays, miR-522 promoted
      GBM cell proliferation, which could be reversed by inhibitor of miR-522. We
      further identified PH domain leucine-rich repeats protein phosphatase-1 (PHLPP1)
      as a putative target of miR-522, which is likely a main contributor to the
      promotion of tumor cell growth observed in our assays. Our results demonstrated
      that miR-522 promoted tumor cell proliferation and hence may represent a novel
      therapeutically relevant cellular target to treatment of GBM patients. 

PMID- 25776497
TI  - Regulatory Tweak/Fn14 signaling pathway as a potent target for controlling bone
      loss.
AB  - Metabolic bone diseases, such as rheumatoid arthritis (RA) and osteoporosis, are
      characterized as imbalance between bone formation and bone resorption, leading to
      bone microarchitecture damage and bone mineral density loss. Bone loss is huge
      threat for older people's health, which imposes a heavy financial burden on
      patients and their families. However, the effectiveness of bone loss treatment in
      clinical practice is limited. With the understanding of the molecular and
      cellular regulators and mediators of bone remodelling, we know that some
      signaling pathways and inflammatory cytokines play important roles in the
      development of RA and osteoporosis. The increasing evidence showed that tumor
      necrosis factor (TNF)-like weak inducer of apoptosis (Tweak)/fibroblast growth
      factor-inducible 14 (Fn14) signalling controls a variety of cellular activities
      in biological processes, such as proliferation, differentiation, and apoptosis
      and has diverse biological functions in pathological mechanisms like inflammation
      that are associated with the process of bone metabolism. Recent studies suggest
      that the interactions between Tweak/Fn14 play critical roles in osteoblast and
      osteoclast differentiation and apoptosis, especially in those rheumatoid
      arthritis patients. These findings suggest that interventions targeting
      Tweak/Fn14 signaling pathway to regulate osteoblast-osteoclast coupling according
      to its biological effects, which results in promoting osteoblast formation and
      inhibiting osteoclast resorption, may be a promising approach for bone loss
      prevention and treatment in the near future. 

PMID- 25776498
TI  - Role of cyclooxygenase-2 in the development of interstitial fibrosis in kidneys
      following unilateral ureteral obstruction in mice.
AB  - Unilateral ureteral obstruction (UUO) induced tubulointerstitial fibrosis in
      kidneys mimics the pathogenesis of chronic kidney diseases and is considered a
      suitable model for studying the mechanisms leading to fibrosis. To study the role
      of cyclooxygenase-2 (COX-2) in kidney fibrosis, we investigated whether a
      selective COX-2 inhibitor, celecoxib, affected renal interstitial fibrosis during
      UUO in mice. To induce UUO, the left proximal ureter was ligated in male C57BL/6
      mice. The mice were fed a diet with or without celecoxib from the day of UUO
      induction. Following UUO, the renal pelvis was observed to be dilated and the
      kidney cortex was significantly thinner than that of sham-operated mice.
      Immunofluorescent staining of type I, III, and IV collagen in UUO kidneys
      revealed that interstitial collagen deposition was significantly increased in the
      celecoxib-treated group. Expression of type I, III, and IV collagen in UUO
      kidneys was also significantly higher in the celecoxib-treated group than in the
      vehicle-treated group. In the celecoxib-treated group, mRNA levels of TGF
      beta/FGF-2 were also significantly higher than those in the vehicle-treated
      group. The present study demonstrates that COX-2 plays a protective role against
      fibrosis in UUO kidneys and suggests that supplementation of COX-2 products, such
      as PG analogues, will be a good option for preventing interstitial fibrosis. 

PMID- 25776499
TI  - The cancer pain related factors affected by celecoxib together with cetuximab in
      head and neck squamous cell carcinoma.
AB  - Pain is the most disruptive influence on the quality of prognosis among head and
      neck squamous cell carcinoma (HNSCC) patients. The development of pain is closely
      associated with tumor growth and inflammation in the cancer patients. Notably,
      cyclooxygenase-2 (COX-2) is an important mediator during inflammation. Celecoxib,
      a selective inhibitor of COX-2, was hailed as a promising chemopreventive agent
      for HNSCC. Dose-dependent cardiac toxicity limits long-term use of celecoxib.
      However, the toxicity can be diminished by lowering the dosage. In this study, we
      hypothesized that a combinatory strategy to reduce cancer pain via two distinct
      pathways, tumor grown inhibition and inflammation blockade, which would enhance
      analgesia effect induced by HNSCC. We found that treatment of cetuximab (C225), a
      monoclonal anti-epidermal growth factor receptor (EGFR) antibody, with low-dose
      celecoxib results in a more pronounced anticancer effect in HNSCC than either
      agent alone. More noticeably, the combination could downregulate the
      phosphorylation of constitutively active extracellular signal regulated kinase
      (ERK) in CAL-27 and Fadu cells. Furthermore, combination therapy enhancing S
      phase arrest and downregulating cyclin D1 was observed in Fadu cells. The COX-2
      expression was significantly blocked by celecoxib combined with C225, and other
      cancer pain related factors, such as ET-1 and NGF, was also downregulated by
      combination treatment. Taken together, these results strongly suggest that
      combination of celecoxib with C225 holds potential as a new therapy strategy in
      developing cancer pain treatment in HNSCC. 

PMID- 25776500
TI  - Prognostic value of mesothelin expression in patients with triple negative and
      HER2-positive breast cancers.
AB  - PURPOSE: Mesothelin is a cell surface glycoprotein that is overexpressed in
      various malignancies. Recent studies have revealed that mesothelin plays an
      oncogenic role in tumor growth and drug resistance through the Wnt/NF
      kappaB/PI3K/Akt signaling pathways. Herein, the expression of mesothelin in HER2
      positive and triple-negative breast cancer (TNBC) has been correlated with
      prognosis. METHODS: A total of 430 patients with breast cancer treated between
      2006 and 2013 were retrospectively reviewed; of these, 123 cases were considered
      TNBC (n=71; 58%) or were positive for HER2 (n=52; 42%). Mesothelin expression was
      assessed by immunohistochemistry. RESULTS: Of the patients with TNBC, 30 (42.3%)
      were positive for mesothelin expression, compared to only two (3.8%) of the HER2
      positive cases. As most HER2-positive tumors were negative for mesothelin
      staining, statistical analysis was not performed. Median overall survival (OS)
      was 70.1 months for patients with TNBC, whereas median OS was 70.1 months, in the
      mesothelin-positive group and 74.5 months in mesothelin-negative group,
      respectively. Strong correlation was seen between mesothelin expression and tumor
      grade in patients with TNBC (P<0.005). In a multivariable Cox proportional
      hazards model, mesothelin expression was not independently associated with OS in
      patients with TNBC. CONCLUSIONS: Expression of mesothelin was observed in 42.3%
      of patients with TNBC and demonstrated a strong association with tumor grade.
      However, its expression was not correlated with prognosis.

PMID- 25776501
TI  - Targeted concurrent chemoradiotherapy, by using improved microcapsules that
      release carboplatin in response to radiation, improves detectability by computed
      tomography as well as antitumor activity while reducing adverse effect in vivo.
AB  - PURPOSE: The effect of alginate-hyaluronate microcapsules that release
      carboplatin in response to radiation was improved by adding ascorbic acid (AA).
      MATERIALS AND METHODS: Four measures of the effectiveness of the microcapsules
      were evaluated: 1) release of carboplatin in response to radiation in vitro and
      in vivo; 2) detectability of their accumulation by computed tomography (CT) in
      vivo; 3) enhancement of antitumor effects in vivo; and 4) reduction of adverse
      effects in vivo. RESULTS: There were significant increases in the rupture of
      microcapsules by adding AA in vitro. Subcutaneously injected microcapsules around
      the tumor could be detected by using CT and the alteration of CT-values
      correlated with the accumulation of the microcapsules. Those microcapsules
      released carboplatin and resulted in synergistic antitumor effect with
      concomitant radiation. With the encapsulation of carboplatin, chemotherapeutic
      effects were still observed two weeks after treatment. However, addition of AA
      did not result in increased antitumor effect in vivo. A reduction in adverse
      effects was observed with the encapsulation of carboplatin, through localization
      of carboplatin around the tumor. CONCLUSION: Addition of AA to the materials of
      microcapsules did not result in increasing antitumor effect. However
      encapsulation of carboplatin will be useful as a clinical cancer-therapy option.

PMID- 25776502
TI  - Quercetin derivatives regulate melanosome transportation via EPI64 inhibition and
      elongate the cell shape of B16 melanoma cells.
AB  - 4'-O-beta-D-glucopyranosyl-quercetin-3-O-beta-D-glucopyranosyl-(1->4)-beta-D
      glucopyranoside (3C4'GQ), first isolated from Helminthostachys zeylanica root
      extract, was synthesized as a compound that stimulates intracellular
      melanogenesis. 3-O-methylquercetin (3MQ) and 3,4',7-O-trimethylquercetin
      (34'7TMQ) were synthesized as compounds that enhance extracellular melanin
      formation. The formation of dendrites and the expression of EBP50-PDZ interactor
      of 64 kDa (EPI64) relating to melanin transportation were investigated using B16
      melanoma cells treated with 3C4'GQ, 3MQ, or 34'7TMQ in order to understand the
      mechanism underlying the observed activities. The influence of 3C4'GQ on the
      increase of intracellular melanin contents enhanced the expression of EPI64,
      exhibited no dendrite elongation activity, and inhibited melanin transportation.
      On the other hand, the increase of extracellular melanin content by 3MQ and
      34'7TMQ inhibited the expression of EPI64 and formed elongated cells to stimulate
      melanin transportation.

PMID- 25776503
TI  - Induction of vascular leak syndrome by tumor necrosis factor-alpha alone.
AB  - Although TNF-alpha possesses promising anticancer activity, clinical application
      is limited partly due to cardiovascular toxicities. TNF-alpha effects on vessels
      are likely related to vascular toxicity, but much remains poorly understood.
      Similarly, IL-2 is an attractive treatment option for cancers but its clinical
      use is limited by the side effect of vascular leak syndrome (VLS). We report here
      that TNF-alpha alone can trigger VLS. Administration of recombinant TNF-alpha
      induced VLS in normal mice and TNF-alpha transgenic mice exhibited VLS.
      Perivascular infiltrates in the lungs and specific cytokines in serum were
      observed in VLS-induced mice. This study shed a new light on the critical role of
      the TNF-alpha in IL-2-induced or non IL-2-induced VLS and provides important
      points to TNF-alpha therapy. 

PMID- 25776504
TI  - MTDH/AEG-1-based DNA vaccine suppresses metastasis and enhances chemosensitivity
      to paclitaxel in pelvic lymph node metastasis.
AB  - OBJECTIVE: MTDH/AEG-1 could act as an oncogene by regulating cellular
      transformation, proliferation, invasion, metastasis, and angiogenesis. This study
      aims to explore the mechanism by which MTDH/AEG-1 inhibits cancer growth and
      metastasis and enhances chemosensitivity. METHODS: Mouse model was established
      using orally immunized mice exposed to attenuated Salmonella containing vectors
      carrying full length MTDH/AEG-1 gene, and we were able to enhance the immune
      response and inhibit the growth and metastasis of prostate cancer through
      activation of cellular and humoral immunities and induction of CD8+ T cells.
      Immunohistochemistry and TUNEL assay, CD4+ and CD8+ T cell analysis by flow
      cytometry, HE staining, RT-PCR analysis, Western-blot analysis and quantitative
      polymerase chain reaction were performed. RESULTS: The MTDH/AEG-1 gene vaccine
      induced the anti-tumor function of cytotoxic T lymphocytes and CD8+ T cells and
      inhibited tumor growth and metastasis of prostate cancer. In the therapy model,
      the MTDH/AEG-1 gene vaccine significantly enhanced chemosensitivity to
      paclitaxel, inhibited tumor growth, promoted tumor cell apoptosis, and prolonged
      the survival time of tumor-bearing mice without any apparent side effects.
      CONCLUSIONS: Our results demonstrated that MTDH/AEG-1-based DNA vaccines could
      used for the treatment of prostate cancer in terms of the inhibition of tumor
      growth, the lifespan of tumor-bearing animals. Combined with chemotherapy,
      MTDH/AEG-1-based DNA vaccines may produce highly favorable outcomes in the
      prevention and treatment of prostate cancer, suggesting the immune efficacy of
      MTDH/AEG-1-based DNA should be further analyzed in other cancers.

PMID- 25776505
TI  - Novel taspine derivative 12k inhibits cell growth and induces apoptosis in lung
      cell carcinoma.
AB  - Taspine is an active compound in anticancer agent development. 12k was
      synthesized with taspine as lead compound bearing biphenyl scaffold and showed
      potent anticancer activity. Here, we investigated the effect of taspine
      derivative 12k on A549 lung cells. We showed that 12k not only decreased
      significantly A549 cell viability, A549 cell colony formation but also impaired
      A549 cell migration. Moreover, 12k treatment blocked cell cycle progression by
      increasing cell number in S phase to 42.80% for 6 MUmol/L vs. 28.86% for control
      while decreasing cell number in G1 phase. Accordingly, this was associated with
      an increase protein expression of cyclin E and a decrease protein expression of
      cyclin D1, cyclin B1 and its associated CDK1 (cdc2). Meanwhile, we found that 12k
      induced A549 cell apoptosis, which was closely associated with the effect of the
      Bcl-2 family. Increase of Bad, Bak and Bax expression levels, decrease of Bcl-2
      and Mcl-1 expression levels were observed. SiRNA knockdown of c-myc in A549 cells
      significantly attenuated tumor inhibition effects of 12k. In conclusion, our
      results demonstrate that 12k has an inhibitory effect on growth of A549 cell by
      inducing cell cycle arrest and apoptosis.

PMID- 25776506
TI  - Tramadol hydrochloride: pharmacokinetics, pharmacodynamics, adverse side effects,
      co-administration of drugs and new drug delivery systems.
AB  - Tramadol hydrochloride (TrHC) is a synthetic analgesic drug exhibiting opioid and
      non-opioid properties, acting mainly on the central nervous system. It has been
      mostly used to treat pain, although its use to treat anxiety and depression has
      also been documented. These properties arise from the fact that they inhibit
      serotonin (5-HT) reuptake augmenting 5-HT concentration on the synaptic cleft.
      Despite this, TrHC has also been described to have several side effects which are
      mainly due to its fast metabolization and excretion which in turn requires
      multiple doses per day. To surpass this limitation, new pharmaceutical
      formulations are being developed intending the protection, target and sustained
      delivery as well as a reduction on daily dose aiming a reduction on the side
      effects. In the present work we have revised the efficacy, safety, biological and
      adverse effects of TrHC, and the added value of developing a novel drug delivery
      system for topical administration. 

PMID- 25776507
TI  - Distinct lncRNA expression profiles in the prefrontal cortex of SD rats after
      exposure to methylphenidate.
AB  - Methylphenidate (MPH) is a central nervous system stimulant that is widely used
      to treat attention deficit hyperactivity disorder (ADHD) and has been shown to
      improve attention, cognitive function and behaviors in both patients and animal
      models of ADHD. Even among normal healthy people, MPH can facilitate the
      consolidation of memories and improve declarative memory. Using microarray
      techniques, we aimed to find new pharmacology profile of MPH. A Lat maze
      experiment showed that locomotor activity and non-selective attention were
      affected by 2 weeks of exposure to MPH. Then, we identified long non-coding RNA
      (lncRNA) signatures in the prefrontal cortex of rats; 461 up-regulated lncRNAs
      and 97 down-regulated lncRNAs were found in the MPH-exposed group compared with
      the control group using fold-change >1.5. GO and KEGG pathway analyses indicated
      biological functions related to the metabolism of neural chemical compounds and
      nerve cell development. Furthermore, we reported changes in uc.173+ related to
      the UBE2B gene, which may affect neurite outgrowth and axonal regeneration. At
      the same time, MRAK081997 associated with the DHFR gene may be involved in axon
      regeneration in the rodent central nervous system through DNA methylation. Our
      study showed distinct expression profiles of lncRNAs in the normal rat prefrontal
      cortex after exposure to MPH, offering information for further research of MPH
      and may suggesting a new therapeutic target for ADHD. 

PMID- 25776508
TI  - Autologous cytokine-induced killer cell therapy in lung cancer patients: a
      retrospective study.
AB  - Cytokine-induced killer (CIK) cells have the ability to kill tumor cells in vitro
      and in vivo. This study aimed to evaluate the clinical effect of adjuvant
      immunotherapy with CIK cells on the prognosis of lung cancer patients. In the
      present study, we investigated the clinical outcomes of autologous CIK cell
      immunotherapy for patients with lung cancer in a case-control study. Our study
      included 60 patients who received chemotherapy combined with autologous CIK cell
      adoptive immunotherapy in CIK treatment group and 60 patients who received
      chemotherapy alone in the control group. Progression-free survival (PFS) and
      overall survival (OS) of these two groups were evaluated. After 14 days of
      incubation in vitro, the percentages of CD3(+), CD3(+)CD8(+), CD3(+)CD56(+) and
      CD3(-)CD56(+) were significantly increased (P<0.05). The clinical symptoms of 60
      patients were apparently improved. No severe toxicity and side effects were
      observed in the CIK treatment group. The 3-year, 5-year PFS rates were 44.7% and
      26.8% and the 3-year, 5-year OS rates were 74% and 62% in the CIK group,
      respectively, which were significantly improved compared to that in the control
      group. The median PFS and OS in the CIK group were significantly improved than
      those in the control group (PFS, 24 months vs. 14 months, P=0.014; OS, 72 months
      vs. 44 months, P=0.006). Our results indicated that autologous CIK cells can
      efficiently improve the immunological status and prolong PFS and OS in patients
      with lung cancer. 

PMID- 25776509
TI  - Hypercysteinemia promotes atherosclerosis by reducing protein S-nitrosylation.
AB  - Protein S-nitrosylation plays important role in the regulation of cardiovascular
      functions in nitric oxide (NO) Pathway. Hypercysteinemia (HHcy) is an
      independently risk factor for atherosclerosis. We hypothesized that HHcy promotes
      atherosclerosis by reducing level of vascular protein S-nitrosylation. The aim of
      present study is to investigate effect of HHcy on vascular protein S
      nitrosylation. A total of 45 male apoE-/- mice were randomly divided into three
      groups. The control group was fed a Western-type diet. The HHcy group was fed a
      diet containing 4.4% L-methionine, and the HHcy+NONOate group was fed a diet
      containing 4.4% L-methionine and administrated NONOate (ip). Human umbilical vein
      endothelial cells were performed for in vitro experiment. Plasma lipids were
      measured every 4 weeks. After 12 weeks, aortic atherosclerotic lesion areas were
      detected as well as cellular components. The levels of plasma homocysteine (Hcy)
      and NO were measured. S-nitrosylation was detected using immunofluorescence, and
      further confirmed by biotin switch method. We found that compared with the
      control group, Hcy levels, and atherosclerotic plaque, and content of vascular
      smooth muscle cells and macrophages in lesions significantly increased, and
      levels of NO significantly decreased in the HHcy group. However, NONOate reverses
      this effect. In addition, Hcy significantly reduced protein S-nitrosylation in
      human umbilical vein endothelial cells. This reduction of protein S-nitrosylation
      was accompanied by reduced levels of NO. Our results suggested that Hcy promoted
      atherosclerosis by inhibiting vascular protein S-nitrosylation.

PMID- 25776510
TI  - Epigallocatechin-3-gallate attenuates transforming growth factor-beta1 induced
      epithelial-mesenchymal transition via Nrf2 regulation in renal tubular epithelial
      cells.
AB  - Transforming growth factor-beta1 (TGF-beta1) induced epithelial-mesenchymal
      transition (EMT) plays an important role in renal fibrotic process regulation.
      Epigallocatechin-3-gallate (EGCG) exerts a protective effect against acute renal
      damage through its anti-oxidative effect by activating the Nrf2 signaling
      pathway. This study aims to investigate whether EGCG prevents TGF-beta1 induced
      EMT and whether this effect acts via the Nrf2-mediated suppression of TGF-beta1
      signaling. MTT was used for cytotoxicity of EGCG examination and Western blotting
      and immunofluorescence were used for protein expression analysis. Results showed
      that EGCG prevented TGF-beta1 mediated EMT and Smad 2 and Smad 3 phosphorylation
      in a dose dependent manner in NRK-52E cells. In addition, EGCG increased Nrf2
      nuclear accumulation. Overexpression of Nrf2 blocked the phosphorylation of Smad
      2 and Smad 3 mediated by TGF-beta1 and decreased protein expression of
      plasminogen activator inhibitor 1 (PAI-1) and alpha-smooth muscle actin (alpha
      SMA). Furthermore, siRNA-mediated knockdown of Nrf2 gene completely blocked the
      effects of EGCG, indicated by the reduced expressions of type I collagen (Col-I)
      and alpha-SMA were restored. In summary, EGCG inhibits TGF-beta1 induced EMT and
      fibrotic proteins expression by Nrf2 activation. This study reveals a possible
      underlying mechanism of the renal protective effects of EGCG, and may provide a
      potential candidate to renal fibrosis therapy. 

PMID- 25776511
TI  - Design and biological activity of epidermal growth factor receptor-targeted
      peptide doxorubicin conjugate.
AB  - The nonspecific toxicity of anticancer drug doxorubicin (DOX) toward both tumor
      and normal cells can result in serious side effects, thereby limiting its
      clinical applications. In this wok, epidermal growth factor receptor (EGFR)
      antagonist peptide GE11 was introduced into DOX structure via a disulfide bond
      which can be cleaved by reduced glutathione (GSH). We have investigated the
      intracellular delivery and in vitro cytotoxicity of GE11-DOX conjugate and free
      DOX in high (SMMC-7721) and low (MCF-7) EGFR expressing cancer cell models. GE11
      DOX accumulated at higher levels in SMMC-7721 cells than in MCF-7 cells, while
      the cellular uptake of free DOX was almost the same in both cells. Furthermore,
      pretreating with anti-EGFR monoclonal antibody reduced intracellular accumulation
      of GE11-DOX in SMMC-7721, indicating the involvement of EGFR pathway in the
      transport of conjugate. Our results suggest that GE11-DOX conjugate has the
      potential to be a therapeutic agent for treating EGFR overexpressing tumor. 

PMID- 25776512
TI  - Resveratrol loaded gelatin nanoparticles synergistically inhibits cell cycle
      progression and constitutive NF-kappaB activation, and induces apoptosis in non
      small cell lung cancer cells.
AB  - PURPOSE: Previously, we reported that the prepared resveratrol (RSV) loaded
      gelatin nanoparticles (GNPs) possessed enhanced anticancer effect than free RSV
      in non-small cell lung carcinoma cells and Swiss albino mice. The present study
      aims to explore the relevant mechanism of cell death induced by the combination
      of RSV-GNPs in NCI-H460 cells. METHODS AND RESULTS: To increase its
      bioavailability and anticancer efficacy, we have encapsulated RSV-GNPs by
      Coacervation method. The detailed methods of preparation and characterization of
      RSV-GNPs were reported in our earlier publication. RSV-GNPs treated cells showed
      a further increased level of lipid peroxidative markers, i.e. TBARS and LHP in
      NCI-H460 cells. Activities of antioxidant enzymes SOD, CAT, GPx and GSH levels
      were decreased upon the treatment with RSV-GNPs in NCI-H460 cells. The nuclear
      fragmentation was evaluated by DAPI staining and data showed condensed apoptotic
      bodies upon treatment with the combination of RSV-GNPs compared to RSV alone
      treatment group. In addition, cell death induced by RSV-GNPs was mainly due to
      apoptosis which was characterized by a nuclear DNA fragmentation in a ladder
      pattern was obtained from the genomic DNA analysis. Moreover, Western blotting
      analysis showed that apoptosis induced by RSV-GNPs is associated with the
      increased Bax, p53, p21, caspase-3 protein levels, and decreased Bcl-2 and NF
      kappaB proteins expression, which indicates the involvement of mitochondria
      dependent apoptosis in the anticancer efficacy of RSV-GNPs in NCI-H460 cells. It
      was also found that this enhanced anticancer efficacy of RSV-GNPs induced cell
      arrest in the G0/G1 phase of cell cycle. CONCLUSIONS: Taken together, the results
      of our study clearly suggested that the cell death induced by the combination of
      RSV-GNPs would involve alteration in expression of p53, p21, caspase-3, Bax, Bcl
      2 and NF-kappaB, indicating oxidative mechanism in NCI-H460 cells. Based on these
      results, it is concluded that GNPs is an ideal way to deliver RSV because of its
      high loading efficiency and superior efficacy in NCI-H460 cells.

PMID- 25776513
TI  - Neurobiology of l-DOPA induced dyskinesia and the novel therapeutic strategies.
AB  - Parkinson's disease (PD) is a neurological disorder characterized by tremors,
      rigidity and bradykinesia. PD is caused by selective degeneration of the
      dopaminergic neurons, which originate in the substantia nigra pars compacta (SNc)
      and project into the striatum. Levodopa is the most effective drug, used in the
      treatment of PD. However, the long-term use of levodopa produce complications
      which are highly disabling fluctuations and dyskinesias and representing one of
      the major challenge to the existing drug therapy of PD. Recent studies has
      indicated that the pulsatile stimulation of striatal postsynaptic receptors led
      to sensitization of dopaminergic receptors which leads to levodopa induced
      dyskinesias. In spite of the extensive research in this field, the pathogenesis
      of levodopa induced dyskinesia is still unclear. In recent years animal models of
      PD has provided important information to understand the effect of specific
      receptors and post-receptor molecular mechanisms underlying the development of
      dyskinetic movements. The present review is aimed to discuss the neurobiological
      mechanisms of levodopa induced dyskinesia and the therapeutic strategies to
      overcome this problem. 

PMID- 25776514
TI  - The effect of immune status, age and genetic background on induction of oral
      tolerance to Actinomyces viscosus in mice.
AB  - The aim of the present study was to determine the effect of immune status, age
      and genetic background on the induction of oral tolerance to Actinomyces
      viscosus. Suppression of delayed type hypersensitivity (DTH) response and antigen
      specific serum antibody levels could be induced in DBA/2 mice intragastrically
      and systemically immunized with A. viscocus, suggesting the induction of oral
      tolerance. In contrast, this immune suppression could be abrogated if the animals
      had been systemically immunized prior to the induction of oral tolerance with the
      same bacterium. Long-term systemic immunization prior to intragastric
      immunization with A. viscocus suppressed DTH response only. Cell transfer of this
      group of animals also suppressed DTH response in the donors, indicating the
      action of suppressor cells for inhibition of DTH response. Furthermore, oral
      tolerance to A. viscocus failed to occur in mice aged at 3 days and 1, 2, 4, 6
      and 36 weeks old. Mice bearing H-2(d) haplotype were the most susceptible to oral
      tolerization, followed by H-2(b) and H-2(k). Therefore, the results of the
      presence study suggest that the induction of oral tolerance to A. viscosus in
      mice may be dependence on the immune status and genetic background but not age.

PMID- 25776515
TI  - Fucosyltransferase IV (FUT4) as an effective biomarker for the diagnosis of
      breast cancer.
AB  - Specific enzymes are involved in altered glycosylation of cancer.
      Fucosyltransferase IV (FUT4) is associated with the proliferation and metastasis
      of breast cancer. The application of FUT4 assay in the serum has not been
      reported yet. Here, the expression level of FUT4 in the breast cancer patient's
      tissues (n=60) was analyzed by immunohistochemistry (IHC) and the secreted FUT4
      in blood serum samples (n=225) was detected by enzyme-linked immunosorbent assay
      (ELISA). Using low metastatic MCF-7 and high metastatic MDA-MB-231 breast cancer
      cell lines, FUT4 expression was also detected by reverse transcription-polymerase
      chain reaction (RT-PCR), Western blot and immunofluorescent staining. The
      conventional cancer biomarkers cancer antigen (CA15.3) and carcinoembryonic
      antigen (CEA) was analyzed by Elecsys-electrochemical immune assay (ECLIA) to
      compare specificity and sensitivity with that of FUT4. We have observed a
      significant high expression of FUT4 in breast cancer tissues and serums as
      compared to the normal tissues (P<0.01) and control serums (P<0.05). FUT4
      expression was increased in MDA-MB-231 cells vs. that in MCF-7 cells.
      Furthermore, the results of receiver operating characteristic (ROC) analysis was
      shown, area under curve of FUT4 (AUC=0.784) was higher than that of CA15.3
      (AUC=0.468) and CEA (AUC=0.563). The relation analysis is indicated FUT4 is
      significantly correlated with CA15.3 (r=0.234, P<0.05) and there is no
      significant correlation with CEA. In conclusion, this study suggests that FUT4
      can serve as novel biomarker in the diagnosis and prognosis of breast cancer. 

PMID- 25776516
TI  - A new fluorescent based screening system for high throughput screening of drugs
      targeting HBV-core and HBsAg interaction.
AB  - The existing screening systems for anti-hepatitis B virus (anti-HBV) drug
      discovery is time-consuming mainly due to the laborious detection system it is
      using. A new fluorescence based screening system for high throughput anti-HBV
      drug discovery was created by tagging hepatitis B surface antigen (HBsAg) with
      monomeric red fluorescent protein and hepatitis B virus (HBV) core protein with
      enhanced green fluorescent protein. The two constructs were co-transfected on to
      Hep3B cells and the transfection was stabilized by fluorescent activated cell
      sorter (FACS). The fusion proteins expressed through the secretory protein
      pathway as evidenced by localization with ER-Tracker and tubulin tracker. The new
      system has given analogues results like that of conventional enzyme-linked
      immunosorbent assay (ELISA). Hence it can be of very high potential for large
      scale drug screening systems. 

PMID- 25776517
TI  - [Neoadjuvant chemotherapy in triple-negative breast cancer: is there a role for
      platinum?].

PMID- 25776518
TI  - Effects of osteoarthritis and pathological walking on contact stresses in femoral
      cartilage.
AB  - Osteoarthritis is a widespread abnormality in synovial joints leading to
      increasing pain and potential work disability in middle-aged and older
      populations. A primary cause of osteoarthritis is related to damages from high
      local stresses combined with insufficient self-healing of cartilage. In this
      framework, it is the goal of the present contribution to offer a
      thermodynamically consistent simulation of a highly anisotropic, heterogeneous,
      osmotic swelling and poroviscoelastic model of healthy and osteoarthritic
      articular cartilage based on the Theory of Porous Media. Physiological and
      pathological loading patterns are included by means of multi-body system
      calculations on patients. The contact stresses at the cartilage surface are
      represented by means of three-dimensional and simplified stereographic views of
      the femoral head. For normal walking, the stress peaks are higher in the
      degenerated case than in the healthy case. Interestingly, pathological walking
      combined with degenerated cartilage tissue minimises the occurrence of high local
      stresses. 

PMID- 25776519
TI  - Semi-stochastic cell-level computational modelling of cellular forces:
      application to contractures in burns and cyclic loading.
AB  - A phenomenological model is formulated to model cellular forces on extracellular
      material. The model is capable of modelling both expansion and contractile
      forces. This work is based on the assumption of linear elasticity, which allows a
      superposition argument to arrive at fundamental expressions for cellular forces.
      It is also shown how the cellular forces can be implemented using different
      strategies, as well as an extension to cellular point sources. Illustrations are
      given for modelling a (permanent) contraction (e.g. a contracture) of burns and
      for cyclic loading by the cells. 

PMID- 25776520
TI  - Mast cells are required for phototolerance induction and scratching abatement.
AB  - Dermal mast cells protect the skin from inflammatory effects of ultraviolet (UV)
      radiation and are required for UV-induced immune suppression. We sought to
      determine a potential mechanistic role of mast cells in reducing the sensitivity
      to UV radiation (i.e. phototolerance induction) through photohardening. We
      administered single UV exposures as well as a chronic UV irradiation regime to
      mast cell-deficient Kit(W-Sh/W-Sh) mice and their controls. The chronic
      irradiation protocol was similar to that given for prophylaxis in certain
      photodermatoses in humans. Compared to controls, UV-exposed Kit(W-Sh/W-Sh) mice
      were more susceptible to epidermal hyperplasia and dermal oedema which was linked
      to blood vessel dilation. Unexpectedly, Kit(W-Sh/W-Sh) mice exhibited an
      excessive scratching behaviour following broadband UVB plus UVA or solar
      simulated UV irradiation at doses far below their minimal skin-swelling dose.
      Protection from this UV-induced scratching phenotype was dependent on mast cells,
      as engraftment of bone marrow-derived cultured mast cells abated it entirely.
      Kit(W-Sh/W-Sh) mice were entirely resistant to phototolerance induction by
      photohardening treatment. Compared to controls, these mice also showed reduced
      numbers of regulatory T cells and neutrophils in the skin 24 h after UV
      irradiation. While it is well known that mast cell-deficient mice are resistant
      to UV-induced immune suppression, we have discovered that they are prone to
      develop photo-itch and are more susceptible to UV-induced epidermal hyperplasia
      and skin oedema. 

PMID- 25776521
TI  - Task-based image quality evaluation of iterative reconstruction methods for low
      dose CT using computer simulations.
AB  - Iterative reconstruction (IR) methods for x-ray CT is a promising approach to
      improve image quality or reduce radiation dose to patients. The goal of this work
      was to use task based image quality measures and the channelized Hotelling
      observer (CHO) to evaluate both analytic and IR methods for clinical x-ray CT
      applications. We performed realistic computer simulations at five radiation dose
      levels, from a clinical reference low dose D0 to 25% D0. A fixed size and
      contrast lesion was inserted at different locations into the liver of the XCAT
      phantom to simulate a weak signal. The simulated data were reconstructed on a
      commercial CT scanner (SOMATOM Definition Flash; Siemens, Forchheim, Germany)
      using the vendor-provided analytic (WFBP) and IR (SAFIRE) methods. The
      reconstructed images were analyzed by CHOs with both rotationally symmetric (RS)
      and rotationally oriented (RO) channels, and with different numbers of lesion
      locations (5, 10, and 20) in a signal known exactly (SKE), background known
      exactly but variable (BKEV) detection task. The area under the receiver operating
      characteristic curve (AUC) was used as a summary measure to compare the IR and
      analytic methods; the AUC was also used as the equal performance criterion to
      derive the potential dose reduction factor of IR. In general, there was a good
      agreement in the relative AUC values of different reconstruction methods using
      CHOs with RS and RO channels, although the CHO with RO channels achieved higher
      AUCs than RS channels. The improvement of IR over analytic methods depends on the
      dose level. The reference dose level D0 was based on a clinical low dose
      protocol, lower than the standard dose due to the use of IR methods. At 75% D0,
      the performance improvement was statistically significant (p < 0.05). The
      potential dose reduction factor also depended on the detection task. For the
      SKE/BKEV task involving 10 lesion locations, a dose reduction of at least 25%
      from D0 was achieved. 

PMID- 25776522
TI  - [Declared dead? Recommendations regarding integrated care from the perspective of
      German statutory health insurance].
AB  - The traditional separation of health care into sectors in Germany causes
      communication problems that hinder continuous, patient-oriented care. This is
      most evident in the transition from inpatient to outpatient care. That said,
      there are also breaks in the flow of information, a lack of supply, or even
      incorrect information flowing within same-sector care. The transition from a
      division of functions into sectors to a patient-oriented process represents a
      change in the paradigm of health care that can only be successfully completed
      with considerable effort. Germany's statutory health insurance (SHI) funds play a
      key role here, as they are the contracting parties as well as the financiers of
      integrated care, and are strategically located at the center of the development
      process.The objective of this article is to explore how Germany's SHI funds view
      integrated care, what they regard as being the drivers of and barriers to
      transitioning to such a system, and what recommendations they can provide with
      regard to the further development of integrated care. For this purpose semi
      structured interviews with board members and those responsible for implementing
      integrated care into the operations of ten SHI funds representing more than half
      of Germany's SHI-insured population were conducted. According to the
      interviewees, a better framework for integrated care urgently needs to be
      developed and rendered more receptive to innovation.Only in this way will the
      widespread stagnation of the past several years be overcome. The deregulation of
      S 140a-d SGB V and the establishment of a uniform basis for new forms of care in
      terms of a new innovation clause are among the central recommendations of this
      article. The German federal government's innovation fund was met with great hope,
      but also implied risks. Nonetheless, the new law designed to strengthen health
      care overall generated high expectations.

PMID- 25776523
TI  - Systematics, biogeography, and character evolution of Deutzia (Hydrangeaceae)
      inferred from nuclear and chloroplast DNA sequences.
AB  - The genus Deutzia (Hydrangeaceae), containing ca. 60 species circumscribed in
      three sections, is disjunctly distributed in eastern Asia and Central America
      (Mexico). Although the genus is well delimited, its subdivisions into sections
      and series have not been the subject of an explicit test of monophyly based on
      molecular data. A comprehensive examination of the evolutionary relationships
      within the genus is thus still lacking. We present a fossil-calibrated, molecular
      phylogeny of Deutzia based on two nuclear ribosomal DNA (ITS and 26S) and three
      chloroplast DNA regions (matK, rbcL, and trnL-F intergenic spacer). Within this
      framework, we examine character evolution in petal arrangement, filament shape,
      and the number of stamens, and infer the ancestral area and biogeographic history
      of the genus. Our molecular phylogeny suggests that Deutzia is monophyletic. Two
      major clades are recovered: one composed of the species of sect. Neodeutzia from
      Mexico, and the other containing all remaining Deutzia species of sections
      Mesodeutzia and Deutzia from SW China and Northeast Asia. The latter two Asian
      sections were each revealed to be polyphyletic. The induplicate petals, 2-dentate
      filaments, and polystemonous androecia are inferred to be ancestral character
      states. Biogeographic reconstructions suggest a Northeast Asian origin for the
      genus and subsequent spread to Mexico during the Oligocene and to SW China during
      the Miocene. Based on our results, a new infrageneric classification of Deutzia
      inferred from molecular phylogeny is required. We propose to merge sections
      Mesodeutzia and Deutzia to ensure the monophyly at the sectional level. Cooling
      trends during the Oligocene resulted in isolation, separating eastern Asian and
      Mexican taxa, while the warm period during the middle Miocene stimulated the
      diversification from Northeast Asia to SW China. The uplift in the Qinghai
      Tibetan Plateau and monsoon regimes are important in promoting high species
      diversification of Deutzia in SW China. 

PMID- 25776524
TI  - Regioselective access to CF3S-substituted dihydrofurans from homopropargylic
      alcohols with trifluoromethanesulfenamide.
AB  - A facile access to 4-((trifluoromethyl)thio)-2,3-dihydrofurans from unprotected
      homopropargylic alcohols in high regioselectivity is reported. This method is the
      first example of using a free hydroxy group as a nucleophile to complete a
      trifluoromethylthiolation/cyclization protocol with an alkyne in moderate to
      excellent yields. 

PMID- 25776525
TI  - Decoding vibrational states of Concanavalin A amyloid fibrils.
AB  - Amyloid and amyloid-like fibrils are a general class of protein aggregates and
      represent a central topic in life sciences for their involvement in several
      neurodegenerative disorders and their unique mechanical and supramolecular
      morphological properties. Both their biological role and their physical
      properties, including their high mechanical stability and thermodynamic inertia,
      are related to the structural arrangement of proteins in the aggregates at
      molecular level. Significant variations may exist in the supramolecular
      organization of the commonly termed cross-beta structure that constitutes the
      amyloid core. In this context, a fine knowledge of the structural details in
      fibrils may give significant information on the assembly process and on possible
      ways of tuning or inhibiting it. Here we propose a simple method based on the
      combined use of Fourier transform infrared spectroscopy and Fourier transform
      Raman spectroscopy to accurately reveal structural details in the fibrillar
      aggregates, side-chain exposure and intermolecular interactions. Interestingly,
      coupled analysis of mid-infrared spectra reveals antiparallel beta-sheet
      orientation in ConA fibrils. We also report the comparison between THz absorption
      spectra of Concanavalin A in its native and fibrillar state at different
      hydration levels, allowing obtaining corroboration of peaks assignation in this
      range and information on the effect of amyloid supramolecular arrangement on the
      network dynamics of hydration water. 

PMID- 25776527
TI  - Quinolinic acid/tryptophan ratios predict neurological disease in SIV-infected
      macaques and remain elevated in the brain under cART.
AB  - Activation of the kynurenine pathway (KP) of tryptophan catabolism likely
      contributes to HIV-associated neurological disorders. However, KP activation in
      brain tissue during HIV infection has been understudied, and the effect of
      combination antiretroviral therapy (cART) on KP induction in the brain is
      unknown. To examine these questions, tryptophan, kynurenine, 3-hydroxykynurenine,
      quinolinic acid, and serotonin levels were measured longitudinally during SIV
      infection in the striatum and CSF from untreated and cART-treated pigtailed
      macaques. Messenger RNA (mRNA) levels of KP enzymes also were measured in the
      striatum. In untreated macaques, elevations in KP metabolites coincided with
      transcriptional induction of upstream enzymes in the KP. Striatal KP induction
      was also temporally associated-but did not directly correlate-with serotonin
      losses in the brain. CSF quinolinic acid/tryptophan ratios were found to be the
      earliest predictor of neurological disease in untreated SIV-infected macaques,
      outperforming other KP metabolites as well as the putative biomarkers interleukin
      6 (IL-6) and monocyte chemoattractant protein-1 (MCP-1). Finally, cART did not
      restore KP metabolites to control levels in the striatum despite the control of
      the virus, though CSF metabolite levels were normalized in most animals. Overall,
      these results demonstrate that cerebral KP activation is only partially resolved
      with cART and that CSF QUIN/TRP ratios are an early, predictive biomarker of CNS
      disease. 

PMID- 25776528
TI  - Nucleation and growth of condensate in nanoporous materials.
AB  - We consider the adsorption-desorption cycles of water and of three hydrocarbons
      on MCM-41 and on SBA-15. We show that during the desorption portion of a cycle,
      when the condensate is still at the mouth of the pores, in equilibrium, and the
      pressure, P, is the minimum value reached before pore-emptying begins, the
      contact angle is zero. This value of the contact angle is used with the Kelvin
      equation to calculate the pore radius of each of the mesoporous silicas
      considered. The standard deviations in the values are found to differ by only a
      few percent. We propose a method for predicting the size of adsorbed-molecular
      clusters that must be formed in the pores to initiate condensate formation there.
      Once formed, the condensate grows spontaneously to the pore mouth. If the vapour
      phase pressure when this condition is reached is also P, the adsorption
      desorption cycle is reversible. Three of the eight systems considered meet this
      condition and their adsorption-desorption cycles are experimentally reversible. 

PMID- 25776526
TI  - Central and peripheral markers of neurodegeneration and monocyte activation in
      HIV-associated neurocognitive disorders.
AB  - HIV-associated neurocognitive disorders (HAND) affect up to 50 % of HIV-infected
      adults, independently predict HIV morbidity/mortality, and are associated with
      neuronal damage and monocyte activation. Cerebrospinal fluid (CSF) neurofilament
      subunits (NFL, pNFH) are sensitive surrogate markers of neuronal damage in
      several neurodegenerative diseases. In HIV, CSF NFL is elevated in individuals
      with and without cognitive impairment, suggesting early/persistent neuronal
      injury during HIV infection. Although individuals with severe cognitive
      impairment (HIV-associated dementia (HAD)) express higher CSF NFL levels than
      cognitively normal HIV-infected individuals, the relationships between severity
      of cognitive impairment, monocyte activation, neurofilament expression, and
      systemic infection are unclear. We performed a retrospective cross-sectional
      study of 48 HIV-infected adults with varying levels of cognitive impairment, not
      receiving antiretroviral therapy (ART), enrolled in the CNS Anti-Retroviral
      Therapy Effects Research (CHARTER) study. We quantified NFL, pNFH, and monocyte
      activation markers (sCD14/sCD163) in paired CSF/plasma samples. By examining
      subjects off ART, these correlations are not confounded by possible effects of
      ART on inflammation and neurodegeneration. We found that CSF NFL levels were
      elevated in individuals with HAD compared to cognitively normal or mildly
      impaired individuals with CD4+ T-lymphocyte nadirs <=200. In addition, CSF NFL
      levels were significantly positively correlated to plasma HIV-1 RNA viral load
      and negatively correlated to plasma CD4+ T-lymphocyte count, suggesting a link
      between neuronal injury and systemic HIV infection. Finally, CSF NFL was
      significantly positively correlated with CSF pNFH, sCD163, and sCD14,
      demonstrating that monocyte activation within the CNS compartment is directly
      associated with neuronal injury at all stages of HAND.

PMID- 25776529
TI  - First Selective Small Molecule Inhibitor of FGFR4 for the Treatment of
      Hepatocellular Carcinomas with an Activated FGFR4 Signaling Pathway.
AB  - Aberrant signaling through the fibroblast growth factor 19 (FGF19)/fibroblast
      growth factor receptor 4 (FGFR 4) signaling complex has been shown to cause
      hepatocellular carcinoma (HCC) in mice and has been implicated to play a similar
      role in humans. We have developed BLU9931, a potent and irreversible small
      molecule inhibitor of FGFR4, as a targeted therapy to treat patients with HCC
      whose tumors have an activated FGFR4 signaling pathway. BLU9931 is exquisitely
      selective for FGFR4 versus other FGFR family members and all other kinases.
      BLU9931 shows remarkable antitumor activity in mice bearing an HCC tumor
      xenograft that overexpresses FGF19 due to amplification as well as a liver tumor
      xenograft that overexpresses FGF19 mRNA but lacks FGF19 amplification.
      Approximately one third of patients with HCC whose tumors express FGF19 together
      with FGFR4 and its coreceptor klotho beta (KLB) could potentially respond to
      treatment with an FGFR4 inhibitor. These findings are the first demonstration of
      a therapeutic strategy that targets a subset of patients with HCC. SIGNIFICANCE:
      This article documents the discovery of BLU9931, a novel irreversible kinase
      inhibitor that specifically targets FGFR4 while sparing all other FGFR paralogs
      and demonstrates exquisite kinome selectivity. BLU9931 is efficacious in tumors
      with an intact FGFR4 signaling pathway that includes FGF19, FGFR4, and KLB.
      BLU9931 is the first FGFR4-selective molecule for the treatment of patients with
      HCC with aberrant FGFR4 signaling.

PMID- 25776530
TI  - Sex estimation using the femur of Austrians born in the 19th to the middle of the
      20th century.
AB  - Sex estimation of human bones or bone fragments is crucial for the identification
      process of unknown bodies. Regional differences and secular changes lead to ever
      changing osteometric standards for different populations. This study provides
      femoral dimensions of Austrians born between 1822 and 1949 and evaluates the
      discriminating power of sex estimation functions developed by discriminant
      analyses. Depending on the state of preservation up to 127 femora of adult
      individuals (72 females and 55 males) were measured. The following means and
      standard variations were obtained: Maximum length (male: 449.7 +/- 16.7 mm,
      female: 413.9 +/- 16.3 mm), head circumference (148.5 +/- 7.8 vs. 133.8 +/- 6.4
      mm), vertical (46.9 +/- 2.4 vs. 41.9 +/- 2.1 mm), transverse (46.3 +/- 2.4 vs.
      41.5 +/- 2.0 mm), and maximum head diameter (47.0 +/- 2.3 vs. 42.0 +/- 2.1 mm),
      as well as sagittal (28.3 +/- 2.2 vs. 26.2 +/- 1.8 mm), transverse (27.9 +/- 2.5
      vs. 26.1 +/- 2.0 mm), and maximum midshaft diameter (29.2 +/- 2.1 vs. 27.3 +/-
      1.6 mm) and finally condylar width (79.6 +/- 4.6 vs. 71.9 +/- 3.8 mm). The (cross
      validated) discriminant analysis for single measurements showed that the best
      classification is obtained using femur head dimensions, with correct sexing rates
      between 84.8 % for the circumference and 87.8 % for the maximum diameter. The
      maximum length achieved a similarly high rate of correct classification with 86.5
      %, whereas the rate for the condylar width (80.6 %) was somewhat lower. The
      potential of midshaft dimensions for sex estimation was substantially weaker
      (62.3 to 70.8 %). With regard to a multivariate analysis, a stepwise selection
      procedure favoured a combination of maximum length and vertical head diameter
      with 90.1 % being correctly classified. A combination of maximum length, maximum
      head diameter and maximum midshaft diameter resulted in an even higher rate of
      91.5 %. These Austrian standards may provide additional possibilities for sexing
      unknown bodies and skeletal remains born in the 19(th) to the middle of the
      20(th) century. 

PMID- 25776531
TI  - Who gets dipyrone (metamizole) in Germany? Prescribing by age, sex and region.
AB  - WHAT IS KNOWN AND OBJECTIVE: Metamizole (dipyrone) is an analgesic that has been
      the focus of considerable controversy regarding its safety. Because of
      potentially life-threatening blood disorders such as agranulocytosis, it has been
      withdrawn in many countries but not in Germany, where prescribing even increased
      over recent years. We aimed to evaluate prescribing of metamizole in Germany with
      respect to age, sex and regional variations. METHODS: Using data of a statutory
      health insurance, we analysed a cohort of 1.7 million persons who were insured at
      least 1 day in each quarter of 2009. Outcome of interest was the outpatient
      prescription prevalence, for example the proportion of persons receiving at least
      one prescription of metamizole. RESULTS AND DISCUSSION: A total of 6.8% received
      metamizole with a higher prescribing prevalence in females (7.8% vs. 6.0%). The
      prevalence increased with age up to 26.7% in persons >=85 years (men: 21.1%; and
      women: 30.4%). We found large regional variations with higher prevalences in the
      northern part of Germany. Most of the prescriptions were issued by general
      practitioners (78.9%). 58.3% were liquid oral formulations with considerable
      regional variations ranging between 32.3% in Mecklenburg-West Pomerania and 67.3%
      in North Rhine-Westphalia. Overall, liquid oral forms are much more often
      prescribed in the western than in the eastern part of Germany. WHAT IS NEW AND
      CONCLUSION: Metamizole - a drug with a relatively narrow indication - is often
      prescribed in Germany with relevant differences by age, sex and region.
      Qualitative studies should clarify reasons for this. Further quantitative
      research should investigate small-area variations, indications and treatment
      durations.

PMID- 25776533
TI  - Verifying the markers of ovarian cancer using RNA-seq data.
AB  - Markers associated with diagnosis, presentation and potential therapeutic targets
      have received widespread attention in ovarian cancer research in the past few
      years. However, the majority of these markers have been investigated
      individually, and the changes in expression and the association between them are
      rarely documented. Next-generation sequencing, also termed RNA-seq when the
      sequencing targets are cDNAs, can provide a whole blueprint of the transcriptome
      of a specific tissue. In the present study, RNA-seq data of human ovarian cancer
      samples were used to verify the expression of known markers and to identify the
      association between them. A total of 563 markers associated with ovarian cancer
      were retrieved from the database of the National Center of Biotechnology
      Information, and used as the target markers. The transcriptome of the ovarian
      tissue of four different tumors, containing tumor presentation and recurrence
      stages, were sequenced using the Illumina GAII platform. Approximately 85.97%
      markers were expressed of the total 563 markers, and the majority of them were
      involved in pathways associated with cancer, signaling and infection. In total,
      85 markers were found to be aberrantly expressed in tumor cells from patients
      with ovarian cancer who had recurrences, including 33 upregulated markers at the
      recurrence stage. Therefore, they may have roles ovarian tumor due to their
      aberrant expression. Differentially expressed markers and the associations
      between them can be assessed by examining the RNA-seq data. These findings may
      provide novel information for further studies on ovarian cancer.

PMID- 25776534
TI  - Amplification of light collection in solid-state dye-sensitized solar cells via
      the antenna effect through supramolecular assembly.
AB  - This study demonstrates that the concept of molecular antenna is a relevant
      strategy to improve the power conversion efficiency of solid-state dye-sensitized
      solar cells by extending their spectral sensitivity over a broad region of the
      solar spectrum. In this work, we have associated a BODIPY antenna to a bi
      chromophoric sensitizer made of a squaraine unit linked to a zinc porphyrin by
      axial ligation onto the zinc. Using steady-state and transient photoluminescence
      spectroscopy, we demonstrate that efficient energy transfers occur from the
      antenna to the dyad, extending its visible photosensitivity. We also show that
      direct electron injection from the antenna to TiO2 is possible. A drastic
      improvement in the device performance by a factor of three is observed under
      illumination using the spiro-OMeTAD molecular glass as the solid-state
      electrolyte, leading to a panchromatic response of the device. The influence of
      the solid-state hole transporter on the supramolecular assembly is also
      discussed. 

PMID- 25776535
TI  - Mitochondrial permeability transition pore (MPTP)-dependent and -independent
      pathways of mitochondrial membrane depolarization, cell shrinkage and
      microparticle formation during platelet apoptosis.

PMID- 25776536
TI  - Persistent Ehrlichia ewingii infection in dogs after natural tick infestation.
AB  - BACKGROUND: Ehrlichia ewingii, which causes disease in dogs and people, is the
      most common Ehrlichia spp. infecting dogs in the United States, but little is
      known about how long E. ewingii infection persists in dogs.
      HYPOTHESIS/OBJECTIVES: To evaluate the persistence of natural infection with E.
      ewingii in dogs. ANIMALS: Four Class A Beagles; no previous exposure to ticks or
      tick-borne infectious agents. METHODS: Dogs were exposed to ticks by weekly walks
      through tick habitat in north central Oklahoma; dogs positive for infection with
      Ehrlichia spp. by sequence-confirmed PCR and peptide-specific serology were
      evaluated for 733 days (D). Whole blood was collected once weekly for PCR, and
      serum was collected once monthly for detection of antibodies to Ehrlichia canis
      (peptide p16), Ehrlichia chaffeensis (indirect fluorescence antibody [IFA] and
      variable-length PCR target [VLPT]), and E. ewingii (peptide p28). RESULTS: All
      dogs (4/4) became infected with Ehrlichia spp. as evidenced by seroconversion on
      IFA to E. chaffeensis (4/4); PCR detection of E. ewingii (4/4) and E. chaffeensis
      (2/4) DNA using both nested and real-time assays; and presence of specific
      antibodies to E. ewingii (4/4) and E. chaffeensis (2/4). Infection with E.
      chaffeensis was not detected after D55. Intermittent E. ewingii rickettsemia
      persisted in 3 of 4 dogs for as long as 733 days. CONCLUSIONS AND CLINICAL
      IMPORTANCE: Our data demonstrate that dogs infected with E. ewingii from tick
      feeding are capable of maintaining infection with this pathogen long-term, and
      may serve as a reservoir host for the maintenance of E. ewingii in nature.

PMID- 25776532
TI  - Trial of early, goal-directed resuscitation for septic shock.
AB  - BACKGROUND: Early, goal-directed therapy (EGDT) is recommended in international
      guidelines for the resuscitation of patients presenting with early septic shock.
      However, adoption has been limited, and uncertainty about its effectiveness
      remains. METHODS: We conducted a pragmatic randomized trial with an integrated
      cost-effectiveness analysis in 56 hospitals in England. Patients were randomly
      assigned to receive either EGDT (a 6-hour resuscitation protocol) or usual care.
      The primary clinical outcome was all-cause mortality at 90 days. RESULTS: We
      enrolled 1260 patients, with 630 assigned to EGDT and 630 to usual care. By 90
      days, 184 of 623 patients (29.5%) in the EGDT group and 181 of 620 patients
      (29.2%) in the usual-care group had died (relative risk in the EGDT group, 1.01;
      95% confidence interval [CI], 0.85 to 1.20; P=0.90), for an absolute risk
      reduction in the EGDT group of -0.3 percentage points (95% CI, -5.4 to 4.7).
      Increased treatment intensity in the EGDT group was indicated by increased use of
      intravenous fluids, vasoactive drugs, and red-cell transfusions and reflected by
      significantly worse organ-failure scores, more days receiving advanced
      cardiovascular support, and longer stays in the intensive care unit. There were
      no significant differences in any other secondary outcomes, including health
      related quality of life, or in rates of serious adverse events. On average, EGDT
      increased costs, and the probability that it was cost-effective was below 20%.
      CONCLUSIONS: In patients with septic shock who were identified early and received
      intravenous antibiotics and adequate fluid resuscitation, hemodynamic management
      according to a strict EGDT protocol did not lead to an improvement in outcome.
      (Funded by the United Kingdom National Institute for Health Research Health
      Technology Assessment Programme; ProMISe Current Controlled Trials number,
      ISRCTN36307479.).

PMID- 25776537
TI  - Topological analysis of the Escherichia coli WcaJ protein reveals a new conserved
      configuration for the polyisoprenyl-phosphate hexose-1-phosphate transferase
      family.
AB  - WcaJ is an Escherichia coli membrane enzyme catalysing the biosynthesis of
      undecaprenyl-diphosphate-glucose, the first step in the assembly of colanic acid
      exopolysaccharide. WcaJ belongs to a large family of polyisoprenyl-phosphate
      hexose-1-phosphate transferases (PHPTs) sharing a similar predicted topology
      consisting of an N-terminal domain containing four transmembrane helices (TMHs),
      a large central periplasmic loop, and a C-terminal domain containing the fifth
      TMH (TMH-V) and a cytosolic tail. However, the topology of PHPTs has not been
      experimentally validated. Here, we investigated the topology of WcaJ using a
      combination of LacZ/PhoA reporter fusions and sulfhydryl labelling by PEGylation
      of novel cysteine residues introduced into a cysteine-less WcaJ. The results
      showed that the large central loop and the C-terminal tail both reside in the
      cytoplasm and are separated by TMH-V, which does not fully span the membrane,
      likely forming a "hairpin" structure. Modelling of TMH-V revealed that a highly
      conserved proline might contribute to a helix-break-helix structure in all PHPT
      members. Bioinformatic analyses show that all of these features are conserved in
      PHPT homologues from Gram-negative and Gram-positive bacteria. Our data
      demonstrate a novel topological configuration for PHPTs, which is proposed as a
      signature for all members of this enzyme family. 

PMID- 25776538
TI  - Immunological blockade of adipocyte inflammation caused by increased matrix
      metalloproteinase-cleaved osteopontin in obesity.
AB  - OBJECTIVE: Osteopontin (OPN) is upregulated in adipose tissue (AT) in obesity and
      contributes to subclinical inflammation, adipocyte dysfunction, and insulin
      resistance. OPN effects can be increased by cleavage by matrix metalloproteinases
      (MMP). This study aimed at investigating the presence of OPN cleavage products in
      human AT in obesity and their impact on adipocyte function and immunological
      blockade of these effects. METHODS: AT of severely obese and control donors was
      investigated for OPN and MMP expression and the presence of OPN cleavage
      fragments. Primary adipocytes were isolated from human donors for in vitro
      investigation of cleaved OPN effects. RESULTS: OPN and MMP-9 expression was
      highly correlated in AT from obese donors, and increased levels of cleaved OPN
      were detected in AT from obese individuals. The in vitro effect of OPN on
      adipocyte inflammation and insulin resistance was enhanced by protease cleavage,
      which could finally be blocked with a monoclonal antibody directed against the
      MMP cleavage site of OPN. CONCLUSIONS: These findings show that MMP cleavage of
      OPN in AT occurs in obesity, thereby enhancing OPN's inflammatory and pro
      diabetic activity on adipocytes. Specifically targeting MMP-cleaved OPN opens
      avenues for prevention and treatment of obesity-induced type 2 diabetes.

PMID- 25776540
TI  - Detection of African swine fever, classical swine fever, and foot-and-mouth
      disease viruses in swine oral fluids by multiplex reverse transcription real-time
      polymerase chain reaction.
AB  - African swine fever (ASF), classical swine fever (CSF), and foot-and-mouth
      disease (FMD) are highly contagious animal diseases of significant economic
      importance. Pigs infected with ASF and CSF viruses (ASFV and CSFV) develop
      clinical signs that may be indistinguishable from other diseases. Likewise,
      various causes of vesicular disease can mimic clinical signs caused by the FMD
      virus (FMDV). Early detection is critical to limiting the impact and spread of
      these disease outbreaks, and the ability to perform herd-level surveillance for
      all 3 diseases rapidly and cost effectively using a single diagnostic sample and
      test is highly desirable. This study assessed the feasibility of simultaneous
      ASFV, CSFV, and FMDV detection by multiplex reverse transcription real-time
      polymerase chain reaction (mRT-qPCR) in swine oral fluids collected through the
      use of chewing ropes. Animal groups were experimentally infected independently
      with each virus, observed for clinical signs, and oral fluids collected and
      tested throughout the course of infection. All animal groups chewed on the ropes
      readily before and after onset of clinical signs and before onset of lameness or
      serious clinical signs. ASFV was detected as early as 3 days postinoculation
      (dpi), 2-3 days before onset of clinical disease; CSFV was detected at 5 dpi,
      coincident with onset of clinical disease; and FMDV was detected as early as 1
      dpi, 1 day before the onset of clinical disease. Equivalent results were observed
      in 4 independent studies and demonstrate the feasibility of oral fluids and mRT
      qPCR for surveillance of ASF, CSF, and FMD in swine populations. 

PMID- 25776541
TI  - Evaluation of three 5' exonuclease-based real-time polymerase chain reaction
      assays for detection of pathogenic Leptospira species in canine urine.
AB  - Leptospirosis is caused by several pathogenic Leptospira species, and is an
      important infectious disease of dogs. Early detection of infection is crucial for
      an effective antibiotic treatment of the disease. Though different polymerase
      chain reaction (PCR) assays have been developed for detection of pathogenic
      Leptospira spp., thorough evaluation of the performance of these assays using dog
      urine samples has not been carried out. In the current study, the performance of
      3 real-time PCR (qPCR) assays was assessed, 1 targeting the 16S ribosomal RNA
      (rRNA) gene and the other 2 targeting the lipL32 gene, a gene for the LipL32
      outer membrane protein. With DNA extracted from laboratory-cultured pathogenic
      Leptospira spp., all 3 qPCR assays showed 100% specificity and had identical
      lower limits of detection. Compared to a conventional, gel-based PCR assay, all 3
      qPCR assays were 100-fold more sensitive. There was a 100% agreement in the
      results of the 3 assays when tested on urine samples collected aseptically from
      30 dogs suspected for leptospirosis. However, when tested on 30 urine samples
      that were collected by the free-catch method, the 16S rRNA-based assay falsely
      detected 13.3% of the samples as positive for pathogenic Leptospira spp.
      Nucleotide sequence analysis of the amplified DNA fragments showed that the assay
      resulted in false positives because of unrelated bacteria. All urine samples
      collected from 100 apparently healthy dogs at a local animal shelter tested
      negative for pathogenic Leptospira spp. These results highlight the importance of
      sample-specific validation of PCR-based diagnostic assays and the application of
      appropriately validated assays for more reliable pathogen detection. 

PMID- 25776542
TI  - Acute phase proteins in healthy goats: establishment of reference intervals.
AB  - Acute inflammatory processes can trigger increased production of acute phase
      proteins (APPs) that can be useful biomarkers of inflammation. APPs are diverse
      and include proteins involved in coagulation, opsonization, iron regulation, and
      limitation of tissue injury. Haptoglobin, serum amyloid A, and alpha-1 acid
      glycoprotein have been proposed as useful APPs in goats. APPs can differ markedly
      by species, therefore species-specific reference intervals and studies are
      necessary. The objective of this study was to determine species-specific
      reference intervals for 4 APPs in goats. Haptoglobin, serum amyloid A,
      lipopolysaccharide binding protein, and alpha-1 acid glycoprotein were measured
      in in 54 clinically normal adult goats. APPs were measured using goat-specific
      commercial enzyme-linked immunosorbent assay kits. Results were analyzed by 1-way
      analysis of variance to compare sexes and breeding status. Reference Value
      Advisor was used to calculate reference limits according to the IFCC-CLSI
      guidelines. Only 1 APP was found to vary in healthy animals; serum haptoglobin
      was increased in lactating animals and decreased in pregnant does in their second
      trimester when compared with open, nonlactating does. No sex-based differences
      were seen for any of the APPs measured. We report normal reference intervals for
      4 serum APPs that may be useful as disease markers. Haptoglobin should be
      interpreted with caution in animals with unknown pregnancy status. Further
      studies are needed to determine whether these APPs are useful biomarkers in goat
      disease states. 

PMID- 25776543
TI  - Validation and application of a canine-specific automated high-sensitivity C
      reactive protein assay.
AB  - Measurement of low concentrations of C-reactive protein (CRP) in dogs has
      previously been performed with nonautomated assays. The aim of this study was to
      validate an automated high-sensitivity CRP (hsCRP) assay, developed by modifying
      a routinely used canine-specific immunoturbidimetric CRP test (cCRP).
      Imprecision, linearity under dilution, limit of blank (LOB), limit of detection
      (LOD), and limit of quantification (LOQ) were determined for the hsCRP test, as
      well as the presence of prozone effect and interferences. The imprecision,
      measured as intra-assay variation, was <=2.7%. The assay was acceptably linear
      under dilution. An analytically relevant prozone effect was present for samples
      with CRP concentration >150 mg/L, and there were mild interferences from
      hemolysis and lipemia. The LOB, LOD, and LOQ were 0.10 mg/L, 0.22 mg/L, and 0.50
      mg/L, respectively. A method comparison study with a canine-specific enzyme
      linked immunosorbent assay (ELISA) was performed, showing poor agreement between
      the hsCRP test and the ELISA. An additional aim of the study was to apply the
      hsCRP test to clinical research samples. Serum samples from 7 dogs undergoing
      ovariohysterectomy were collected pre- and postoperatively, and CRP was measured
      with both the cCRP and hsCRP assay. The expected postoperative increase in CRP
      was detected earlier with the hsCRP test, compared with the cCRP test. The hsCRP
      assay was further applied on samples from 6 lean and 9 overweight dogs. There was
      no significant difference in CRP concentration between the groups (P = 0.06). In
      conclusion, the hsCRP test had acceptable analytical performance, and the assay
      was successfully applied to clinical research samples. 

PMID- 25776544
TI  - Detection of Babesia canis vogeli and Hepatozoon canis in canine blood by a
      single-tube real-time fluorescence resonance energy transfer polymerase chain
      reaction assay and melting curve analysis.
AB  - A real-time fluorescence resonance energy transfer polymerase chain reaction
      (qFRET PCR) coupled with melting curve analysis was developed for detection of
      Babesia canis vogeli and Hepatozoon canis infections in canine blood samples in a
      single tube assay. The target of the assay was a region within the 18S ribosomal
      RNA gene amplified in either species by a single pair of primers. Following
      amplification from the DNA of infected dog blood, a fluorescence melting curve
      analysis was done. The 2 species, B. canis vogeli and H. canis, could be detected
      and differentiated in infected dog blood samples (n = 37) with high sensitivity
      (100%). The detection limit for B. canis vogeli was 15 copies of a positive
      control plasmid, and for H. canis, it was 150 copies of a positive control
      plasmid. The assay could simultaneously distinguish the DNA of both parasites
      from the DNA of controls. Blood samples from 5 noninfected dogs were negative,
      indicating high specificity. Several samples can be run at the same time. The
      assay can reduce misdiagnosis and the time associated with microscopic
      examination, and is not prone to the carryover contamination associated with the
      agarose gel electrophoresis step of conventional PCR. In addition, this qFRET PCR
      method would be useful to accurately determine the range of endemic areas or to
      discover those areas where the 2 parasites co-circulate. 

PMID- 25776545
TI  - Occurrence of Coxiella burnetii and Chlamydiales species in abortions of domestic
      ruminants and in wild ruminants in Hungary, Central Europe.
AB  - Coxiella burnetii and certain members of the Chlamydiales order are zoonotic,
      intracellular, Gram-negative bacteria, with abortigenic potential in ruminants.
      These pathogens have a broad host range and worldwide geographical distribution.
      The current study aimed to reveal the importance of C. burnetii and Chlamydiales
      spp. in abortions in domestic ruminants and their occurrence in wild ruminants
      with real-time polymerase chain reaction (qPCR) assays, histology, and
      immunohistochemical staining (IHC). From the 111 abortion cases of domestic
      ruminants examined, C. burnetii was detected in 33 placenta samples (cattle, n =
      22; sheep, n = 10; goat, n = 1), and members of the Chlamydiales order were
      detected in 32 placenta samples (cattle, n = 14; sheep, n = 16; goat, n = 2)
      using qPCR. Coinfection with both C. burnetii and Chlamydiales spp. were
      identified in 12 cases (cattle, n = 3; sheep, n = 8; goat, n = 1) out of the qPCR
      positive samples. The presence of the relevant antigen was confirmed by IHC in 20
      cases (C. burnetii, n = 2, in sheep; Chlamydiaceae, n = 17, in sheep [n = 15] and
      goat [n = 2]; and both pathogens in 1 sheep). Coxiella burnetii was identified in
      2.2% (2/91) of the wild ruminants, but the samples were negative by IHC.
      Uncultured Chlamydiales spp. were detected in 4.4% (4/91) of the placenta samples
      by qPCR. In conclusion, Q fever is widespread among domestic ruminants in
      Hungary, and, in several cases, C. burnetii was implicated as the primary cause
      of abortions. Waddlia chondrophila, Parachlamydia spp., and uncultured
      Chlamydiales spp. were present only sporadically in samples from cattle and wild
      ruminants. 

PMID- 25776546
TI  - Development and use of a real-time polymerase chain reaction assay for the
      detection of Ophidiomyces ophiodiicola in snakes.
AB  - Fungal pathogens threatening the conservation of wildlife are becoming
      increasingly common. Since 2008, free-ranging snakes across North America have
      been experiencing a marked increase in the prevalence of snake fungal disease
      associated with Ophidiomyces ophiodiicola. Diagnosis has historically relied on
      histology, microbiology, and conventional polymerase chain reaction (PCR). More
      sensitive methods are needed to adequately characterize the epidemiology. The
      current study describes the development of a real-time PCR (qPCR) assay for
      detecting a segment of the internal transcribed spacer 1 region between the 18S
      and 5.8S ribosomal RNA gene. The assay was able to detect as few as 1.05 * 10(1)
      gene copies per reaction. An additional 4 positive cases were detected when
      comparing a conventional PCR (n = 3) and the qPCR (n = 7) when used on swab
      samples from 47 eastern massasauga rattlesnakes. The newly developed assay is a
      sensitive and specific tool for surveillance and monitoring in the conservation
      of free-ranging snakes. 

PMID- 25776547
TI  - Cytologic findings and diagnostic yield in 92 dogs undergoing fine-needle
      aspiration of the pancreas.
AB  - The diagnosis of pancreatic disease in small animal veterinary patients is
      complicated by nonspecific clinical signs and the limitations of diagnostic
      testing. Pancreatic cytology is a potential diagnostic tool, but safety and
      diagnostic yield are not well characterized in large patient cohorts. We
      hypothesized that pancreatic fine-needle aspiration (FNA) in dogs would
      frequently generate diagnostic-quality samples and subsequent adverse medical
      events would be uncommon. Ninety-two client-owned dogs undergoing pancreatic FNA
      for clinical diagnostic evaluation were identified retrospectively by a computer
      search for pancreatic cytology submissions. Archived slides were reviewed by a
      single board-certified clinical pathologist using a predetermined descriptive
      scheme. Medical records were reviewed for adverse events 48 hr following FNA, for
      concurrent procedures and diagnosis in patients with adverse events and for
      histology results. Diagnostic yield was calculated as the % cases in which a
      cytologic diagnosis could be achieved; correlation with histology or other
      confirmatory testing was determined when possible. Diagnostic yield was 73.5%,
      and the major pathologic process identified cytologically correlated with
      confirmatory testing in 10 out of 11 cases. There were 7 adverse events, all in
      dogs with significant comorbidities or undergoing other invasive procedures.
      Pancreatic FNA in dogs has a good diagnostic yield and a low rate of clinical
      complications in a large case series of dogs. Correlation of cytology and
      histology results was high in a limited number of cases. 

PMID- 25776548
TI  - Detection of arenavirus in a peripheral odontogenic fibromyxoma in a red tail boa
      (Boa constrictor constrictor) with inclusion body disease.
AB  - A captive bred red tail boa (Boa constrictor constrictor) was presented with a
      large intraoral mass originating from the buccal gingiva, attached to the right
      dentary teeth row. Based on the clinical features and histological examination,
      the diagnosis of a peripheral odontogenic fibromyxoma was made. Sections of liver
      biopsies and circulating lymphocytes contained relatively few eosinophilic
      intracytoplasmic inclusion bodies, indistinguishable from those observed in
      inclusion body disease-affected snakes. Inclusion bodies were not observed in
      cells comprising the neoplastic mass. Using reverse transcription polymerase
      chain reaction (RT-PCR), arenavirus was detected in the neoplastic tissue. Two
      years after surgical removal of the mass, recurrence of the neoplastic lesion was
      observed. Numerous large inclusion body disease inclusions were abundantly
      present in the neoplastic cells of the recurrent fibromyxoma. Sections of liver
      biopsies and circulating lymphocytes contained relatively few intracytoplasmic
      inclusions. The RT-PCR revealed the presence of arenavirus in blood, a liver
      biopsy, and neoplastic tissue. The present case describes the co-occurrence of an
      arenavirus infection and an odontogenic fibromyxoma in a red tail boa. 

PMID- 25776549
TI  - Development and validation of a novel hydrolysis probe real-time polymerase chain
      reaction for agamid adenovirus 1 in the central bearded dragon (Pogona
      vitticeps).
AB  - Agamid adenovirus 1 (AgAdv-1) is a significant cause of disease in bearded
      dragons (Pogona sp.). Clinical manifestations of AgAdv-1 infection are variable
      and often nonspecific; the manifestations range from lethargy, weight loss, and
      inappetence, to severe enteritis, hepatitis, and sudden death. Currently,
      diagnosis of AgAdv-1 infection is achieved through a single published method:
      standard nested polymerase chain reaction (nPCR) and sequencing. Standard nPCR
      with sequencing provides reliable sensitivity, specificity, and validation of PCR
      products. However, this process is comparatively expensive, laborious, and slow.
      Probe hybridization, as used in a TaqMan assay, represents the best option for
      validating PCR products aside from the time-consuming process of sequencing. This
      study developed a real-time PCR (qPCR) assay using a TaqMan probe-based assay,
      targeting a highly conserved region of the AgAdv-1 genome. Standard curves were
      generated, detection results were compared with the gold standard conventional
      PCR and sequencing assay, and limits of detection were determined. Additionally,
      the qPCR assay was run on samples known to be positive for AgAdv-1 and samples
      known to be positive for other adenoviruses. Based on the results of these
      evaluations, this assay allows for a less expensive, rapid, quantitative
      detection of AgAdv-1 in bearded dragons. 

PMID- 25776550
TI  - Traditional Uses of Medicinal Plants from the Canadian Boreal Forest for the
      Management of Chronic Pain Syndromes.
AB  - OBJECTIVE: Chronic pain is more prevalent in indigenous populations who often
      prefer traditional remedies over allopathic drugs. Our objective was to
      investigate the traditional uses of medicinal plants from the Canadian boreal
      forest for the management of chronic pain syndromes. METHODS: We reviewed the
      most extensive database on medicinal plants used by aboriginal people of the
      Canadian boreal forest to investigate the plants used in the management of 3 of
      the most common chronic pain syndromes: arthritis/rheumatism; back pain; and
      headache/migraine. We also reviewed the pharmacology and phytochemistry
      literature to investigate concordance with indigenous knowledge. RESULTS: A total
      of 114 medicinal plant species were reported, of which 27 (23.5%) were used to
      treat more than 1 chronic pain syndrome. Pharmacological or phytochemical
      evidence to explain plant function as chronic pain remedy was available in the
      literature for only 38 species (33%), with several species reported to have anti
      inflammatory and analgesic properties effective in treating chronic pain
      syndromes. CONCLUSIONS: Our study showed the potential of boreal plants as
      alternative and complementary medicines for the treatment of chronic pain
      syndromes that could be enhanced by further research on efficacy and safety
      issues.

PMID- 25776551
TI  - Effectiveness of core biopsy for screen-detected breast lesions under 10 mm:
      implications for surgical management.
AB  - BACKGROUND: Technical advances have improved the detection of small mammographic
      lesions. In the context of mammographic screening, accurate sampling of these
      lesions by percutaneous biopsy is crucial in limiting diagnostic surgical
      biopsies, many of which show benign results. METHODS: Women undergoing core
      biopsy between January 1997 and December 2007 for <10-mm lesions are included.
      Patient demographics, imaging features and final histology were tabulated.
      Performance indices were evaluated. RESULTS: This audit includes 803 lesions <10
      mm. Based on core histology, 345 women (43.0%) were immediately cleared of
      malignancy and 300 (37.4%) were referred for definitive cancer treatment. A
      further 157 women (19.6%) required diagnostic surgical biopsy because of
      indefinite or inadequate core results or radiological-pathological discordance,
      and one woman (0.1%) needed further imaging in 12 months. The open biopsies were
      malignant in 46 (29.3%) cases. The positive predictive value of malignant core
      biopsy was 100%. The negative predictive value for benign core results was 97.7%,
      and the false-negative rate was 2.6%. The lesion could not be visualized after
      core biopsy in 5.1% of women and in 4.0% of women with malignant core biopsies
      excision specimens did not contain residual malignancy. Excessive delays in
      surgery because of complications of core biopsy were not reported. CONCLUSION:
      Even at this small size range, core biopsy evaluation of screen-detected breast
      lesions is highly effective and accurate. A lesion miss rate of 3.1% and under
      representation of lesions on core samples highlight the continued need for
      multidisciplinary collaboration and selective use of diagnostic surgical biopsy.

PMID- 25776552
TI  - Stomatin-like protein 2 is required for in vivo mitochondrial respiratory chain
      supercomplex formation and optimal cell function.
AB  - Stomatin-like protein 2 (SLP-2) is a mainly mitochondrial protein that is widely
      expressed and is highly conserved across evolution. We have previously shown that
      SLP-2 binds the mitochondrial lipid cardiolipin and interacts with prohibitin-1
      and -2 to form specialized membrane microdomains in the mitochondrial inner
      membrane, which are associated with optimal mitochondrial respiration. To
      determine how SLP-2 functions, we performed bioenergetic analysis of primary T
      cells from T cell-selective Slp-2 knockout mice under conditions that forced
      energy production to come almost exclusively from oxidative phosphorylation.
      These cells had a phenotype characterized by increased uncoupled mitochondrial
      respiration and decreased mitochondrial membrane potential. Since formation of
      mitochondrial respiratory chain supercomplexes (RCS) may correlate with more
      efficient electron transfer during oxidative phosphorylation, we hypothesized
      that the defect in mitochondrial respiration in SLP-2-deficient T cells was due
      to deficient RCS formation. We found that in the absence of SLP-2, T cells had
      decreased levels and activities of complex I-III2 and I-III2-IV(1-3) RCS but no
      defects in assembly of individual respiratory complexes. Impaired RCS formation
      in SLP-2-deficient T cells correlated with significantly delayed T cell
      proliferation in response to activation under conditions of limiting glycolysis.
      Altogether, our findings identify SLP-2 as a key regulator of the formation of
      RCS in vivo and show that these supercomplexes are required for optimal cell
      function.

PMID- 25776553
TI  - Molecular Mechanism for the Control of Eukaryotic Elongation Factor 2 Kinase by
      pH: Role in Cancer Cell Survival.
AB  - Acidification of the extracellular and/or intracellular environment is involved
      in many aspects of cell physiology and pathology. Eukaryotic elongation factor 2
      kinase (eEF2K) is a Ca(2+)/calmodulin-dependent kinase that regulates translation
      elongation by phosphorylating and inhibiting eEF2. Here we show that
      extracellular acidosis elicits activation of eEF2K in vivo, leading to enhanced
      phosphorylation of eEF2. We identify five histidine residues in eEF2K that are
      crucial for the activation of eEF2K during acidosis. Three of them (H80, H87, and
      H94) are in its calmodulin-binding site, and their protonation appears to enhance
      the ability of calmodulin to activate eEF2K. The other two histidines (H227 and
      H230) lie in the catalytic domain of eEF2K. We also identify His108 in calmodulin
      as essential for activation of eEF2K. Acidification of cancer cell
      microenvironments is a hallmark of malignant solid tumors. Knocking down eEF2K in
      cancer cells attenuated the decrease in global protein synthesis when cells were
      cultured at acidic pH. Importantly, activation of eEF2K is linked to cancer cell
      survival under acidic conditions. Inhibition of eEF2K promotes cancer cell death
      under acidosis. 

PMID- 25776554
TI  - Involvement of RNA Polymerase III in Immune Responses.
AB  - Inflammation in the tumor microenvironment has many tumor-promoting effects. In
      particular, tumor-associated macrophages (TAMs) produce many cytokines which can
      support tumor growth by promoting survival of malignant cells, angiogenesis, and
      metastasis. Enhanced cytokine production by TAMs is tightly coupled with protein
      synthesis. In turn, translation of proteins depends on tRNAs, short abundant
      transcripts that are made by RNA polymerase III (Pol III). Here, we connect these
      facts by showing that stimulation of mouse macrophages with lipopolysaccharides
      (LPS) from the bacterial cell wall causes transcriptional upregulation of tRNA
      genes. The transcription factor NF-kappaB is a key transcription factor mediating
      inflammatory signals, and we report that LPS treatment causes an increased
      association of the NF-kappaB subunit p65 with tRNA genes. In addition, we show
      that p65 can directly associate with the Pol III transcription factor TFIIIB and
      that overexpression of p65 induces Pol III-dependent transcription. As a
      consequence of these effects, we show that inhibition of Pol III activity in
      macrophages restrains cytokine secretion and suppresses phagocytosis, two key
      functional characteristics of these cells. These findings therefore identify a
      radical new function for Pol III in the regulation of macrophage function which
      may be important for the immune responses associated with both normal and
      malignant cells. 

PMID- 25776555
TI  - Alternative Splicing Shapes the Phenotype of a Mutation in BBS8 To Cause
      Nonsyndromic Retinitis Pigmentosa.
AB  - Bardet-Biedl syndrome (BBS) is a genetic disorder affecting multiple systems and
      organs in the body. Several mutations in genes associated with BBS affect only
      photoreceptor cells and cause nonsyndromic retinitis pigmentosa (RP), raising the
      issue of why certain mutations manifest as a systemic disorder whereas other
      changes in the same gene affect only a specific cell type. Here, we show that
      cell-type-specific alternative splicing is responsible for confining the
      phenotype of the A-to-G substitution in the 3' splice site of BBS8 exon 2A (IVS1
      2A>G mutation) in the BBS8 gene to photoreceptor cells. The IVS1-2A>G mutation
      leads to missplicing of BBS8 exon 2A, producing a frameshift in the BBS8 reading
      frame and thus eliminating the protein specifically in photoreceptor cells. Cell
      types other than photoreceptors skip exon 2A from the mature BBS8 transcript,
      which renders them immune to the mutation. We also show that the splicing of Bbs8
      exon 2A in photoreceptors is directed exclusively by redundant splicing enhancers
      located in the adjacent introns. These intronic sequences are sufficient for
      photoreceptor-cell-specific splicing of heterologous exons, including an exon
      with a randomized sequence. 

PMID- 25776556
TI  - The Human RNA Polymerase I Transcription Terminator Complex Acts as a Replication
      Fork Barrier That Coordinates the Progress of Replication with rRNA Transcription
      Activity.
AB  - In S phase, the replication and transcription of genomic DNA need to accommodate
      each other, otherwise their machineries collide, with chromosomal instability as
      a possible consequence. Here, we characterized the human replication fork barrier
      (RFB) that is present downstream from the 47S pre-rRNA gene (ribosomal DNA
      [rDNA]). We found that the most proximal transcription terminator, Sal box T1,
      acts as a polar RFB, while the other, Sal box T4/T5, arrests replication forks
      bidirectionally. The fork-arresting activity at these sites depends on polymerase
      I (Pol I) transcription termination factor 1 (TTF-1) and a replisome component,
      TIMELESS (TIM). We also found that the RFB activity was linked to rDNA copies
      with hypomethylated CpG and coincided with the time that actively transcribed
      rRNA genes are replicated. Failed fork arrest at RFB sites led to a slowdown of
      fork progression moving in the opposite direction to rRNA transcription. Chemical
      inhibition of transcription counteracted this deceleration of forks, indicating
      that rRNA transcription impedes replication in the absence of RFB activity. Thus,
      our results reveal a role of RFB for coordinating the progression of replication
      and transcription activity in highly transcribed rRNA genes. 

PMID- 25776557
TI  - Sam68 Regulates S6K1 Alternative Splicing during Adipogenesis.
AB  - The requirement for alternative splicing during adipogenesis is poorly
      understood. The Sam68 RNA binding protein is a known regulator of alternative
      splicing, and mice deficient for Sam68 exhibit adipogenesis defects due to
      defective mTOR signaling. Sam68 null preadipocytes were monitored for alternative
      splicing imbalances in components of the mTOR signaling pathway. Herein, we
      report that Sam68 regulates isoform expression of the ribosomal S6 kinase gene
      (Rps6kb1). Sam68-deficient adipocytes express Rps6kb1-002 and its encoded p31S6K1
      protein, in contrast to wild-type adipocytes that do not express this isoform.
      Sam68 binds an RNA sequence encoded by Rps6kb1 intron 6 and prevents
      serine/arginine-rich splicing factor 1 (SRSF1)-mediated alternative splicing of
      Rps6kb1-002, as assessed by cross-linking and immunoprecipitation (CLIP) and
      minigene assays. Depletion of p31S6K1 with small interfering RNAs (siRNAs)
      partially restored adipogenesis of Sam68-deficient preadipocytes. The ectopic
      expression of p31S6K1 in wild-type 3T3-L1 cells resulted in adipogenesis
      differentiation defects, showing that p31S6K1 is an inhibitor of adipogenesis.
      Our findings indicate that Sam68 is required to prevent the expression of p31S6K1
      in adipocytes for adipogenesis to occur. 

PMID- 25776558
TI  - H-ras distribution and signaling in plasma membrane microdomains are regulated by
      acylation and deacylation events.
AB  - H-Ras must adhere to the plasma membrane to be functional. This is accomplished
      by posttranslational modifications, including palmitoylation, a reversible
      process whereby H-Ras traffics between the plasma membrane and the Golgi complex.
      At the plasma membrane, H-Ras has been proposed to occupy distinct sublocations,
      depending on its activation status: lipid rafts/detergent-resistant membrane
      fractions when bound to GDP, diffusing to disordered membrane/soluble fractions
      in response to GTP loading. Herein, we demonstrate that H-Ras sublocalization is
      dictated by its degree of palmitoylation in a cell type-specific manner. Whereas
      H-Ras localizes to detergent-resistant membrane fractions in cells with low
      palmitoylation activity, it locates to soluble membrane fractions in lineages
      where it is highly palmitoylated. Interestingly, in both cases GTP loading
      results in H-Ras diffusing away from its original sublocalization. Moreover,
      tilting the equilibrium between palmitoylation and depalmitoylation processes can
      substantially alter H-Ras segregation and, subsequently, its biochemical and
      biological functions. Thus, the palmitoylation/depalmitoylation balance not only
      regulates H-Ras cycling between endomembranes and the plasma membrane but also
      serves as a key orchestrator of H-Ras lateral diffusion between different types
      of plasma membrane and thereby of H-Ras signaling. 

PMID- 25776559
TI  - Ccr4-Not and TFIIS Function Cooperatively To Rescue Arrested RNA Polymerase II.
AB  - Expression of the genome requires RNA polymerase II (RNAPII) to transcribe across
      many natural and unnatural barriers, and this transcription across barriers is
      facilitated by protein complexes called elongation factors (EFs). Genetic studies
      in Saccharomyces cerevisiae yeast suggest that multiple EFs collaborate to assist
      RNAPII in completing the transcription of genes, but the molecular mechanisms of
      how they cooperate to promote elongation are not well understood. The Ccr4-Not
      complex participates in multiple steps of mRNA metabolism and has recently been
      shown to be an EF. Here we describe how Ccr4-Not and TFIIS cooperate to stimulate
      elongation. We find that Ccr4-Not and TFIIS mutations show synthetically enhanced
      phenotypes, and biochemical analyses indicate that Ccr4-Not and TFIIS work
      synergistically to reactivate arrested RNAPII. Ccr4-Not increases the recruitment
      of TFIIS into elongation complexes and enhances the cleavage of the displaced
      transcript in backtracked RNAPII. This is mediated by an interaction between Ccr4
      Not and the N terminus of TFIIS. In addition to revealing insights into how these
      two elongation factors cooperate to promote RNAPII elongation, our study extends
      the growing body of evidence suggesting that the N terminus of TFIIS acts as a
      docking/interacting site that allows it to synergize with other EFs to promote
      RNAPII transcription. 

PMID- 25776561
TI  - Hypertension: Redox-sensitive transcription factors regulate the renal dopamine
      receptor.

PMID- 25776562
TI  - Hypertension: Complement C1 and beta-catenin in hypertensive arterial
      remodelling.

PMID- 25776563
TI  - An efficient edge-functionalization method to tune the photoluminescence of
      graphene quantum dots.
AB  - An efficient edge-functionalization strategy with high specificity was employed
      to study the effects of conjugated structures on photoluminescence (PL)
      properties of graphene quantum dots (GQDs). Both the experimental results and
      density functional theory (DFT)-based calculations suggested the mechanism for
      conjugated structures in GQDs to tune the band gap of GQDs. 

PMID- 25776560
TI  - Cell regulation by phosphotyrosine-targeted ubiquitin ligases.
AB  - Three classes of E3 ubiquitin ligases, members of the Cbl, Hakai, and SOCS-Cul5
      RING ligase families, stimulate the ubiquitination of phosphotyrosine-containing
      proteins, including receptor and nonreceptor tyrosine kinases and their
      phosphorylated substrates. Because ubiquitination frequently routes proteins for
      degradation by the lysosome or proteasome, these E3 ligases are able to potently
      inhibit tyrosine kinase signaling. Their loss or mutational inactivation can
      contribute to cancer, autoimmunity, or endocrine disorders, such as diabetes.
      However, these ligases also have biological functions that are independent of
      their ubiquitination activity. Here we review relevant literature and then focus
      on more-recent developments in understanding the structures, substrates, and
      pathways through which the phosphotyrosine-specific ubiquitin ligases regulate
      diverse aspects of cell biology. 

PMID- 25776564
TI  - Identification of genetic variations associated with epsilon-poly-lysine
      biosynthesis in Streptomyces albulus ZPM by genome sequencing.
AB  - The biosynthesis of the antibiotic epsilon-poly-lysine (epsilon-PL) in
      Streptomyces albulus is performed by polylysine synthase (pls); however, the
      regulatory mechanism of this process is still unknown. Here, we first obtained
      the complete genome sequence of S. albulus ZPM, which consists of 9,784,577 bp
      and has a GC content of 72.2%. The genome houses 44 gene clusters for secondary
      metabolite biosynthesis, in which 20 gene clusters are involved in the
      biosynthesis of polyketides and nonribosomally synthesized peptides. High
      throughput sequencing was further performed, and genetic variants were identified
      from pooled libraries consisting of the 30 highest-yield mutants or 30 lowest
      yield mutants. More than 350 genetic variants associated with epsilon-PL yield
      have been identified. One hundred sixty-two affected proteins, from important
      metabolic enzymes to novel transcriptional regulators, were identified as being
      related to epsilon-PL synthesis. HrdD, one of the affected genes, is a sigma
      factor that shows the most sensitive response to pH change and contains a non
      synonymous mutation (A132V) in mutant strains with lower epsilon-PL yields.
      Electrophoretic mobility shift assays showed that the pls gene is likely
      regulated by transcriptional activator HrdD. The data obtained in this study will
      facilitate future studies on epsilon-PL yield improvement and industrial
      bioprocess optimization.

PMID- 25776565
TI  - Intrinsic facial nerve tumours of the temporal bone: a proposed management
      guideline.
AB  - OBJECTIVE: The aim of this paper was to propose a guideline for the management of
      intrinsic facial nerve tumours based on our practice and findings in the
      literature. METHOD: A retrospective review of intrinsic facial nerve tumours over
      the last 15 years was performed. Parameters measured included age, presenting
      symptoms, pre- and post-treatment hearing and House-Brackmann grading, tumour
      position, treatment and duration of follow up. RESULTS: A total of 15 patients
      presented with intrinsic facial nerve tumours over the study period. The most
      common presenting complaint was facial symptoms (93.3 per cent), followed by
      hearing loss (46.7 per cent). Three patients with stable facial nerve function
      (House-Brackmann grades II-III) were treated conservatively. Twelve patients
      underwent surgery to treat progressive or recurrent symptoms. Facial function was
      maintained or improved in 60.0 per cent of patients and hearing was preserved in
      66.7 per cent. CONCLUSION: We propose that all stable tumours associated with
      good facial function of grade III or below should be treated conservatively. For
      symptomatic or progressive lesions, tailored surgery depending on the tumour site
      and hearing level should be offered to preserve native nerve function and facial
      musculature. For patients with prolonged paralysis, tumours can be monitored and
      other forms of facial reanimation and support offered.

PMID- 25776566
TI  - Reply: To PMID 25385679.

PMID- 25776567
TI  - Children in rural China enjoyed a significant increase in quality of life from
      2009 to 2011.
AB  - AIM: Little is known about the long-term change in quality of life (QoL) among
      children in rural China. This study longitudinally examined changes and
      predictors of QoL among children in one rural county between 2009 and 2011.
      METHODS: We interviewed 816 children from seven to 16 years of age in 2009 and
      2011 using a range of QoL tools. Multivariate forward stepwise linear regression
      analysis was used to examine the relationships between follow-up QoL and socio
      demographic, family environment and psychosocial factors. RESULTS: Overall QoL
      scores improved significantly from 71.1 +/- 14.6 to 72.8 +/- 16.3 (p = 0.005).
      QoL was positively related to annual family income (beta = 0.14, p < 0.001) and
      baseline QoL (beta = 0.21, p < 0.001) and negatively related to older age (beta =
      -0.19, p < 0.001), being female (beta = -0.08, p = 0.011), being left in the care
      of family members by working parents (beta = -0.09, p = 0.004), negative coping
      styles (beta = -0.10, p = 0.005) and depression (beta = -0.11, p = 0.006).
      CONCLUSION: Quality of life significantly improved among children in rural China
      over a two-year period from 2009 to 2011. It was positively related to annual
      family income and baseline QoL and negatively related to older age, being female,
      being left in the care of family members by working parents, negative coping
      styles and depression.

PMID- 25776568
TI  - Cell biology of the Koji mold Aspergillus oryzae.
AB  - Koji mold, Aspergillus oryzae, has been used for the production of sake, miso,
      and soy sauce for more than one thousand years in Japan. Due to the importance,
      A. oryzae has been designated as the national micro-organism of Japan (Koku-kin).
      A. oryzae has been intensively studied in the past century, with most
      investigations focusing on breeding techniques and developing methods for Koji
      making for sake brewing. However, the understanding of fundamental biology of A.
      oryzae remains relatively limited compared with the yeast Saccharomyces
      cerevisiae. Therefore, we have focused on studying the cell biology including
      live cell imaging of organelles, protein vesicular trafficking, autophagy, and
      Woronin body functions using the available genomic information. In this review, I
      describe essential findings of cell biology of A. oryzae obtained in our study
      for a quarter of century. Understanding of the basic biology will be critical for
      not its biotechnological application, but also for an understanding of the
      fundamental biology of other filamentous fungi. 

PMID- 25776569
TI  - Winter effect on soil microorganisms under different tillage and phosphorus
      management practices in eastern Canada.
AB  - Determining how soil microorganisms respond to crop management systems during
      winter could further our understanding of soil phosphorus (P) transformations.
      This study assessed the effects of tillage (moldboard plowing or no-till) and P
      fertilization (0, 17.5, or 35 kg P.ha(-1)) on soil microbial biomass, enzymatic
      activity, and microbial community structure in winter, in a long-term (18 years)
      corn (Zea mays L.) and soybean (Glycine max L.) rotation established in 1992 in
      the province of Quebec, Canada. Soil samples were collected at 2 depths (0-10 and
      10-20 cm) in February 2010 and 2011 after the soybean and the corn growing
      seasons, respectively. Winter conditions increased the amounts of soil microbial
      biomasses but reduced the overall enzymatic activity of the soil, as compared
      with fall levels after corn. P fertilization had a quadratic effect on the
      amounts of total, bacterial, arbuscular mycorrhizal fungi phospholipid fatty acid
      markers after corn but not after soybean. The soil microbial community following
      the soybean and the corn crops in winter had a different structure. These
      findings suggest that winter conditions and crop-year could be important factors
      affecting the characteristics of the soil microbial community under different
      tillage and mineral P fertilization. 

PMID- 25776570
TI  - Protective effects of intestinal trefoil factor (ITF) on gastric mucosal
      epithelium through activation of extracellular signal-regulated kinase 1/2
      (ERK1/2).
AB  - The rapid repair of gastric mucosa is critical upon exposure to injurious agents.
      Intestinal trefoil factor (ITF) is a member of the trefoil factor family domain
      peptides, which play an important role in the cytoprotection of gastric
      epithelium. However, the underlying molecular mechanisms that are responsible for
      ITF-induced gastric epithelial repair remain unclear. In the present study, we
      demonstrate that ITF enhances the proliferation and migration of GES-1 gastric
      endothelial cells in a dose- and time-dependent manner through the activation of
      extracellular signal-regulated kinase 1/2 (ERK1/2). Furthermore, the ITF-mediated
      protection of GES-1 cells from a NS398 (nonsteroidal anti-inflammatory drug) was
      dependent on the ERK1/2 signaling pathway. Taken together, the results provide a
      mechanistic explanation for ITF-mediated protection of gastric epithelial mucosa
      cells, suggesting that activation of the ERK1/2 signaling pathway may provide a
      new therapeutic strategy for repairing gastric injury.

PMID- 25776571
TI  - SEAP activity serves for demonstrating ER stress induction by glucolipotoxicity
      as well as testing ER stress inhibitory potential of therapeutic agents.
AB  - Endoplasmic reticulum (ER) stress is emerging as a unifying paradigm and one of
      the underlying mechanisms in the genesis of diabetes and its complications. While
      this has prompted the development of ER stress inhibitors, there is a limitation
      in monitoring of ER stress in vitro and in vivo by reliable methodologies. We
      validated the secreted alkaline phosphatase (SEAP) activity as a surrogate marker
      of ER stress in mouse beta-TC6 cells exposed to glucolipotoxicity or tunicamycin
      and studied insulin secretion along with alterations in ER stress markers. SEAP
      activity assay was measured using the Great EscAPe SEAP kit, insulin levels were
      determined by Mercodia reagents and mRNA expression of ER stress markers was
      quantified by real-time PCR. SEAP activity in beta-cells was significantly
      decreased (indicating increased ER stress) on exposure either to
      glucolipotoxicity or tunicamycin. This was accompanied by an increased mRNA
      expression of ER stress markers (GRP-78, PERK, IRE1alpha, ATF6, XBP-1, and CHOP)
      and decreased insulin secretion. Treating the cells with phenylbutyric acid
      normalized SEAP activity, decreased mRNA expression of ER stress markers and
      improved insulin secretion. Interestingly, cells exposed to different classes of
      anti-diabetes agents or compounds such as resveratrol resisted ER stress.
      Methylglyoxal also induces ER stress and this was counteracted by aminoguanidine.
      Out study demonstrates SEAP activity as a novel ER stress monitoring assay to
      investigate the therapeutic value of agents with ER stress inhibitory potential.
      Future studies should focus on the exercise of adopting this reporter assay for
      high-throughput screening mode of drug discovery.

PMID- 25776572
TI  - Modulation of the cancer cell transcriptome by culture media formulations and
      cell density.
AB  - We investigated how varying the composition of cell culture formulations and
      growing cancer cells at different densities might affect tumor cell genotype.
      Specifically, we compared gene expression profiles generated by human MDA-MB-231
      breast cancer cells cultured in different media [minimum essential medium (MEM),
      Dulbecco's modified Eagle's medium (DMEM), or Roswell Park Memorial Institute
      (RPMI)-1640 medium] containing different concentrations of fetal bovine serum
      (FBS) or different sera (equine or bovine) that were grown at different cell
      densities. More than 2,000 genes were differentially modulated by at least a 2
      fold difference when MDA-MB-231 cancer cells were 90% confluent and compared with
      cultures that were 50% confluent. Altering the concentration of serum produced an
      even more pronounced effect on MDA-MB-231 cancer cell gene expression in that
      2,981 genes were differentially expressed in a comparison between cells cultured
      in 0.1% FBS and same cell density cultures that were maintained in 10% FBS. A
      comparison between MDA-MB-231 cancer cells that were 90% confluent in MEM, DMEM,
      or RPMI-1640 media, all containing 10% FBS, resulted in 8,925 differentially
      expressed genes. Moreover, one-quarter (25.6%) of genes from our genome-wide
      expression analysis were expressed at significantly different levels by cells
      grown in MEM, DMEM, or RPMI-1640 media. Genes associated with epithelial-mes
      enchymal transition (EMT) were among the genes that were differentially modulated
      by cells grown in different cell culture formulations and these genes were
      verified at the protein level. Collectively, these results underscore the
      importance of accurate reporting and maintenance of uniform culture conditions to
      ensure reproducible results.

PMID- 25776573
TI  - The association between serum lipids and colorectal neoplasm: a systemic review
      and meta-analysis.
AB  - OBJECTIVE: There have been inconsistent results published regarding the
      relationship between dyslipidaemia and an increased risk of colorectal neoplasia
      (CRN), including colorectal adenoma (CRA) and colorectal cancer (CRC). We
      conducted a meta-analysis to explore the relationship between dyslipidaemia and
      CRN. DESIGN: We identified studies by performing a literature search using
      PubMed, EMBASE and the Science Citation Index through October 2013. SETTING: We
      analysed thirty-three independent studies reporting the association between CRN
      and at least one of the selected lipid components, including total cholesterol
      (TC), TAG, HDL-cholesterol (HDL-C) and LDL-cholesterol (LDL-C). SUBJECTS: CRN
      cases (n 21 809) were identified. RESULTS: Overall, people with high levels of
      serum TAG (risk ratio (RR)=1.08; 95% CI 1.05, 1.12, P<0.00001) and LDL-C
      (RR=1.07; 95% CI 1.00, 1.14, P=0.04) presented an increased prevalence of CRN.
      Subgroup analyses revealed that high levels of serum TC (RR=1.04; 95% CI 1.01,
      1.09, P=0.02), TAG (RR=1.06; 95% CI 1.03, 1.10, P=0.0009) and LDL-C (RR=1.11; 95%
      CI 1.04, 1.19, P=0.003) increased the risk of CRA but not of CRC. No association
      between serum HDL-C and risk for CRN (including CRA and CRC) was observed.
      CONCLUSIONS: Both TAG and LDL-C were significantly associated with an increasing
      prevalence of CRN. High levels of serum TC, TAG and LDL-C were positively
      associated with CRA but not with CRC. No significant association was observed
      between levels of serum HDL-C and CRN.

PMID- 25776577
TI  - Economic crisis and changes in drug use in the Spanish economically active
      population.
AB  - AIMS: To examine changes in the use of alcohol, cannabis and hypnotics/sedatives
      between two periods (before and during Spain's economic crisis), and to identify
      differences in the change between employed and unemployed individuals. DESIGN:
      Using cross-sectional data from four editions of the Spanish Household Survey on
      Alcohol and Drugs, we selected economically active individuals aged 16-64 years
      (total sample = 62 440) and defined two periods, pre-crisis [period 1 (P1) = 2005
      07] and crisis (P2 = 2009-11). Poisson regression models with robust variance
      were fitted to obtain prevalence ratios (PR) of heavy and binge drinking and
      multinomial regression models to obtain relative risk ratios (RRR) of cannabis
      and hypnotic/sedative use between the two periods, also considering the
      interaction between period and employment status. FINDINGS: While the prevalence
      of alcohol use remained stable, heavy drinking declined in P2 in men both overall
      [PR = 0.73; 95% confidence interval (CI) = 0.67-0.79] and in the two age groups
      (16-34 and 35-64 years), and also in women overall (PR = 0.86; 95% CI = 0.75
      0.99) and in the older age group. In contrast, binge drinking increased overall
      in P2 in men (PR = 1.17; 95% CI = 1.12-1.22) and in women (PR = 1.62; 95% CI =
      1.49-1.76), and in both age groups. No differences in the change were observed
      between employed and unemployed individuals. Overall cannabis use remained stable
      in P2, but unemployed men and women of the older age group were more likely to
      have increased sporadic use compared to their employed counterparts (RRR = 2.24;
      95% CI = 1.36-3.68 and RRR = 3.21; 95% CI = 1.30-7.93, respectively).
      Hypnotic/sedative use remained stable in P2 in men, but unemployed men were less
      likely to have increased heavy use in P2 compared with employed men (RRR = 0.69;
      95% CI = 0.49-0.97). In women, heavy use increased in P2 overall and in the older
      age group, irrespective of employment status. CONCLUSION: During a period of
      economic recession in Spain, heavy drinking decreased and binge drinking
      increased. Sporadic cannabis use increased among older unemployed men and women.
      Heavy use of hypnotics/sedatives increased among employed men while older women
      increased use irrespective of employment status.

PMID- 25776578
TI  - Viral gastroenteritis in children in Colorado 2006-2009.
AB  - Acute gastroenteritis accounts for a significant burden of medically attended
      illness in children under the age of five. For this study, four multiplex reverse
      transcription PCR assays were used to determine the incidence of adenovirus,
      astrovirus, coronavirus, norovirus GI and GII, rotavirus, and sapovirus in stool
      samples submitted for viral electron microscopy (EM) to the Children's Hospital
      Colorado. Of 1105 stool samples available, viral RNA/DNA was detected in 247
      (26.2%) of 941 pediatric samples (median age = 2.97 years, 54% male) with 28
      (3.0%) positive for more than one virus. Adenovirus, astrovirus, norovirus GI,
      norovirus GII, rotavirus, and sapovirus were detected in 95 (10.0%), 33 (3.5%), 8
      (0.9%), 90 (9.6%), 49 (5.2%), and 2 (0.2%) of the pediatric samples,
      respectively. No coronaviruses were identified. Sequencing of norovirus positive
      samples indicated an outbreak of norovirus strain GII.4 in 2006 with evidence of
      numerous circulating strains. Multiple samples from the same immunocompromised
      patients demonstrated symptomatic shedding of norovirus for up to 32 weeks and
      astrovirus for 12 weeks. RT-PCR detected 99 of 111 (89%) adenovirus-positive
      samples versus 12 (11%) by EM, and 186 of 192 (97%)
      sapovirus/astrovirus/norovirus-positive samples versus 21 (11%) by EM.
      Noroviruses and adenoviruses are common causes of gastroenteritis in children.
      Immunocompromised patients can be infected with multiple viruses and shed viruses
      in their stools for prolonged periods. This data support the superiority of RT
      PCR compared to EM for diagnosis of viral gastroenteritis.

PMID- 25776579
TI  - Cardiovascular Management Self-efficacy: Psychometric Properties of a New Scale
      and Its Usefulness in a Rehabilitation Context.
AB  - BACKGROUND: Self-efficacy beliefs have been shown to affect various effective
      health-promoting behaviors in patients. Unfortunately, availability of reliable
      and valid measures of self-efficacy in cardiovascular diseases (CVDs) is still
      very limited. PURPOSE: The aims of this study were to present a new scale
      measuring self-efficacy beliefs in managing CVD and to examine its psychometric
      properties. METHODS: The study involved 172 patients (mean age = 66.4 years; SD =
      9.99 years; 76.2% men) undergoing cardiovascular rehabilitation. Various
      psychological factors and CVD severity indicators were collected. RESULTS: An
      Exploratory Structural Equation Model showed that the Cardiovascular Management
      Self-efficacy Scale has three factors: Cardiac Risk Factors, Adherence to
      Therapy, and Recognition of Symptoms. They all showed high internal consistency,
      and good convergent, discriminant, and predictive validity. Furthermore, these
      factors showed significant relations with CVD severity indicators. CONCLUSIONS:
      The Cardiovascular Management Self-efficacy Scale could be a helpful instrument
      to monitor differences during interventions to improve good disease management.

PMID- 25776580
TI  - Considering Cumulative Risk for Cardiovascular Disease in Relation to Cognitive
      Function: a Comment on DeRight et al.

PMID- 25776582
TI  - Eosinophilic meningitis caused by Angiostrongylus cantonensis--a neglected
      disease with escalating importance.
AB  - The rat lungworm Angiostrongylus cantonensis, a food-borne zoonotic parasite, has
      been recognized as the primary pathogen associated with human eosinophilic
      meningitis or eosinophilic meningoencephalitis. This neurotropic nematode has a
      definitive rodent host and a molluscan intermediate host. The adult worms live in
      the pulmonary arteries of rats. Human is a non-permissive, accidental host.
      Transmission to humans is by eating of infected raw or undercooked snails, poorly
      cleaned contaminated vegetables or other infected paratenic hosts such as
      freshwater prawns, crabs, frogs or monitor lizards. Thousands of diagnosed cases
      of eosinophilic meningitis caused by A. cantonensis have been reported worldwide.
      Angiostrongyliasis is of increasing public health importance as globalization
      contributes to the geographical spread and more international travelers encounter
      the disease. The parasite is on the move. It has spread from its traditional
      endemic areas of Asia and the Pacific Basin to the American continent including
      the USA, Brazil and Caribbean islands. Recently, the incidence of human
      infections has increased rapidly. Most reports of the disease are from Thailand
      and Taiwan with increasing reports from mainland China. The rapid global spread
      of the parasite and the emerging occurrence of the infection pose challenges in
      clinical and laboratory diagnosis, and in epidemiology and basic biology.
      Enhanced understanding of the epidemiology of angiostrongyliasis, increased
      public awareness about the risks associated with eating raw or undercooked food,
      and enhanced food safety measures are needed. Therefore, current knowledge on
      various aspects of the parasite and the disease it causes, as well as recent
      epidemiological status together with significant progress in laboratory
      investigation of A. cantonensis infection, are overviewed to promote
      understanding and awareness of this emerging neglected disease. 

PMID- 25776581
TI  - Appointment "no-shows" are an independent predictor of subsequent quality of care
      and resource utilization outcomes.
AB  - BACKGROUND: Identifying individuals at high risk for suboptimal outcomes is an
      important goal of healthcare delivery systems. Appointment no-shows may be an
      important risk predictor. OBJECTIVES: To test the hypothesis that patients with a
      high propensity to "no-show" for appointments will have worse clinical and acute
      care utilization outcomes compared to patients with a lower propensity. DESIGN:
      We calculated the no-show propensity factor (NSPF) for patients of a large
      academic primary care network using 5 years of outpatient appointment data. NSPF
      corrects for patients with fewer appointments to avoid over-weighting of no-show
      visits in such patients. We divided patients into three NSPF risk groups and
      evaluated the association between NSPF and clinical and acute care utilization
      outcomes after adjusting for baseline patient characteristics. PARTICIPANTS: A
      total of 140,947 patients who visited a network practice from January 1, 2007,
      through December 31, 2009, and were either connected to a primary care physician
      or to a primary care practice, based on a previously validated algorithm. MAIN
      MEASURES: Outcomes of interest were incomplete colorectal, cervical, and breast
      cancer screening, and above-goal hemoglobin A1c (HbA1c) and low-density
      lipoprotein (LDL) levels at 1-year follow-up, and hospitalizations and emergency
      department visits in the subsequent 3 years. KEY RESULTS: Compared to patients in
      the low NSPF group, patients in the high NSPF group (n=14,081) were significantly
      more likely to have incomplete preventive cancer screening (aOR 2.41 [2.19-.66]
      for colorectal, aOR 1.85 [1.65-.08] for cervical, aOR 2.93 [2.62-3.28] for breast
      cancer), above-goal chronic disease control measures (aOR 2.64 [2.22-3.14] for
      HbA1c, aOR 1.39 [1.15-1.67] for LDL], and increased rates of acute care
      utilization (aRR 1.37 [1.31-1.44] for hospitalization, aRR 1.39 [1.35-1.43] for
      emergency department visits). CONCLUSIONS: NSPF is an independent predictor of
      suboptimal primary care outcomes and acute care utilization. NSPF may play an
      important role in helping healthcare systems identify high-risk patients.

PMID- 25776583
TI  - Identification of surface proteins of Trichinella spiralis muscle larvae using
      immunoproteomics.
AB  - Trichinella spiralis surface proteins are directly exposed to the host's immune
      system, making them the main target antigens which induce the immune responses
      and may play an important role in the larval invasion and development process.
      The analysis and characterization of T. spiralis surface proteins could provide
      useful information to elucidate the host-parasite interaction, identify the early
      diagnostic antigens and the targets for vaccine. The purpose of this study was to
      identify the surface proteins of T. spiralis muscle larvae by two-dimensional gel
      electrophoresis (2-DE) Western-blot analysis and mass spectrometry. The 2-DE
      results showed that a total of approximately 33 proteins spots were detected with
      molecular weights varying from 10 to 66 kDa and isoelectric point (pI) from 4 to
      7. Fourteen protein spots were recognized by sera of mice infected with T.
      spiralis at 42 dpi or at 18 dpi, and 12 spots were successfully identified by
      MALDI-TOF/TOF-MS, which represented 8 different proteins of T. spiralis. Out of
      the 8 T. spiralis proteins, 5 proteins (partial P49 antigen, deoxyribonuclease II
      family protein, two serine proteases, and serine proteinase) had catalytic and
      hydrolase activity, which might be the invasion-related proteins and the targets
      for vaccine. The 4 proteins (deoxyribonuclease II family protein, serine
      protease, 53 kDa ES antigen and hypothetical protein Tsp_08444) recognized by
      infection sera at 18 dpi might be the early diagnostic antigens for
      trichinellosis. 

PMID- 25776584
TI  - Molecular identification of Leishmania tropica infections in patients with
      cutaneous leishmaniasis from an endemic central of Iran.
AB  - The most common form of the disease is cutaneous leishmaniasis (CL) which is a
      public health and social problem in many countries especially Iran. In endemic
      areas where other diseases with similar clinical symptoms occur, definitive
      diagnosis of CL is very important. The detection and identification of Leishmania
      in infected patients is crucial for achieving a correct treatment and prognosis.
      To our knowledge, this is the first comprehensive study in terms of geographical
      distribution and molecular identification of Leishmania tropica isolates in
      central of Iran. This study was performed between 2010 and 2011, during which 218
      CL suspected patients referred to Shahid Sadoughi University of Medical Sciences
      in Yazd, Iran for confirmation were examined. After microscopic analysis, DNA
      extraction was performed for identification. The molecular target region was ITS1
      gene. Results showed that out of 218 isolates, 102 (46.8%) samples were positive
      for Leishman body using molecular assay. After PCR-RFLP, analysis identified 50
      (49.01%) samples as L. major and 52 (50.98%) as L. tropica. Two samples showed a
      different pattern that were reported as unknown. Among L. tropica, six different
      isolates were identified in this endemic area. Finally, this study showed
      heterozygosity among L. tropica isolates in this endemic area such as some other
      studies from the world. This heterozygosity among the strains may suggest a
      sexual recombination or genetic exchange between strains. 

PMID- 25776585
TI  - Rapid genotyping of Plasmodium vivax Pvs25 and Pv38 genes by using mismatch
      specific endonuclease.
AB  - Mismatch specific endonuclease (MSE) method was used to detect natural
      polymorphisms in Pvs25 and Pv38 genes of Plasmodium vivax. Eighty seven patients
      with P. vivax were recruited in the Republic of Korea (ROK). Pvs25 and Pv38 genes
      were amplified by polymerase chain reaction (PCR), and the PCR amplicons were
      mixed with reference DNA sequences. Following the denaturation and gradual
      annealing, the product mixtures were cleaved by the MSE. Heteroduplex types were
      readily detected by gel electrophoresis, where extra bands with shorter sizes
      would appear from the cleavage. After MSE cleavage of 657- bp product from Pvs25
      mixtures, three genotypes were detected, while Pv38 mixtures with 1220-bp
      products presented two genotypes in ROK isolates. After the MSE cleavage, the
      mismatched samples of Pvs25 and Pv38 were completely sequenced, and the results
      were in complete agreement with the MSE analyses. In conclusion, genotyping of
      Pvs25 and Pv38 with MSE cleavage could be a potential method for the high
      throughput screening of the large field samples. 

PMID- 25776586
TI  - Antibacterial and antifungal activity of solvent extracts from Plumeria obtusa
      Linn.
AB  - Extracts of Plumeria obtusa are widely used in ethnomedicine and have been
      investigated for a variety of biological activities; however, the antimicrobial
      activity of P. obtusa flowers is poorly characterized. In this study, the
      antimicrobial activities of different solvents (petroleum ether, ethyl acetate,
      chloroform, isobutanol and ethanol) extracts from flowers of P. obtusa were
      investigated by a disc diffusion method against Gram-positive bacteria, Gram
      negative bacteria and a fungus. All extracts exhibited growth inhibition of all
      microorganisms at variable degrees as measured by relative zones of inhibition,
      however, the petroleum ether extract was ineffective against Klebsiella pneumonia
      and ethyl acetate and isobutanol extracts were ineffective against Pseudomonas
      aeruginosa. The most susceptible Gram-positive bacterium was Bacillus subtilis
      while the most resistant Gram-positive bacterium was Staphylococcus aureus.
      Erwinia carotovora was the most susceptible Gram-negative bacterium while P.
      aeruginosa was highly resistant among the Gram-negative bacteria. In this study,
      for the first time, we investigated the antimicrobial activity of several
      different solvent extracts from flowers of P. obtusa against a broad spectrum of
      human-pathogenic microorganisms. These compounds warrant further investigation by
      isolation and structural elucidation with the aim to find novel and affordable
      bioactive compounds for the treatment of infectious diseases. 

PMID- 25776587
TI  - Isolation and distribution of mosquito-larvicidal cry genes in Bacillus
      thuringiensis strains native to Saudi Arabia.
AB  - A total of 157 environmental samples were collected from 11 ecological regions
      across Saudi Arabia to isolate native Bacillus thuringiensis (Bt) strains. Bt
      isolates (n=103) were recovered by the 50% (v/v) ethanol treatment method with Bt
      index range of 0.01 to 0.4. Most of Bt isolates showed spherical crystals (54%),
      while, irregular, bi-pyramidal, and spore-attached crystal constituted 27, 16 and
      3% respectively. PCR analysis with eight general and specific dipteran primers of
      Cry and Cyt genes, revealed positive amplification for cry4 & cyt1, and cry4A,
      cry4B and cyt2, and cry 10 and cry 11 genes in 28%, 26%, 22%, and 25% of tested
      strains respectively; whereas cry2 gene was not detected except with the
      reference Bt kurstaki HD-1 strain. Bioassays against Aedes caspuis and Culex
      pipiens larvae indicated that 11 strains displayed better larvicidal activity
      compared with Bacillus thuringiensis H14 (Bti) reference (LC50 0.6 MUg/ml) strain
      against Ae. caspuis, but only two strains (620A & 633R1, LC50 of 0.09 MUg/ml &
      0.064 MUg/ml) that gave significant enhancement. Additionally, one strain (633R1)
      showed LC50 similar to that of Bti H14 (LC50 0.064 MUg/ml) against Cx. pipiens.
      With the exception of cyt primers, sequenced DNA of all positive primers
      amplicons revealed 95 to 99% identity in GenBank with Bacillus thuringiensis
      subsp. israelensis plasmid pBtoxis and also correlated with its SDS-PAGE
      expressed protein profiles analysis. It is hoped that our wild bio-insecticide Bt
      strains can be explored in future in the control of mosquito-vector borne
      diseases in Saudi Arabia. 

PMID- 25776588
TI  - IgG avidity assay: a tool for excluding acute toxoplasmosis in prolonged IgM
      titer sera from pregnant women.
AB  - An accurate diagnosis for toxoplasmosis is crucial for pregnant women as this
      infection may lead to severe sequelae in the fetus. The value of IgG avidity
      assay as a tool to determine acute and chronic toxoplasmosis during pregnancy was
      evaluated in Universiti Kebangsaan Malaysia Medical Centre (UKMMC). In this
      study, 281 serum samples from 281 pregnant women in various trimesters were
      collected. These samples were assayed using specific anti-Toxoplasma IgM and IgG
      antibodies, followed by IgG avidity test. The overall seroprevalence of
      toxoplasmosis in pregnant women was 35.2% (33.5% for anti-Toxoplasma IgG and 1.8%
      for both anti-Toxoplasma IgG and IgM antibodies). Of 5 (1.8%) serum samples
      positive for IgM ELISA, 4 had high-avidity antibodies, suggesting past infection
      and one sample with borderline avidity index. Two samples with low avidity were
      from IgM negative serum samples. The IgG avidity assay exhibited an excellent
      specificity of 97.6% and a negative predictive value (NPV) of 95.6%. The study
      also demonstrated no significant correlation between avidity indexes of the sera
      with IgG (r=0.12, p=0.24) and IgM (r=-0.00, p=0.98), suggesting the complementary
      needs of the two tests for a better diagnosis outcome. These findings highlight
      the usefulness of IgG avidity assay in excluding a recently acquired
      toxoplasmosis infection in IgM-positive serum sample. 

PMID- 25776589
TI  - Cytogenetic, crossing and molecular evidence of two cytological forms of
      Anopheles argyropus and three cytological forms of Anopheles pursati (Diptera:
      Culicidae) in Thailand.
AB  - Nine and 11 isolines of Anopheles argyropus and Anopheles pursati, respectively,
      were established from individual females collected from cow-baited traps, and the
      characteristics of metaphase chromosomes were investigated in their F1-progenies.
      As determined by the different amounts of extra heterochromatin on sex
      chromosomes, 2 types of X (X1, X2) and Y (Y1,Y2), and 2 types of X (X1, X2) and 3
      types of Y (Y1, Y2, Y3) chromosomes were obtained from An. argyropus and An.
      pursati, respectively. These types of sex chromosomes comprised 2 [Forms A (X1,
      Y1) and B (X1, X2, Y2)] and 3 [Forms A (X1, X2, Y1), B (X1, X2, Y2) and C (X2,
      Y3)] karyotypic forms of An. argyropus and An. pursati, respectively. All
      karyotypic forms acquired from An. pursati are new one that were discovered in
      this study, of which Forms A, B and C were found generally in Chiang Mai
      Province, while only 1 isoline of Form B was obtained in Ratchaburi Province.
      Form A was recovered from An. argyropus only in Ubon Ratchathani Province,
      whereas Form B from that species was found commonly in both Ubon Rathchathani and
      Nakhon Si Thammarat Provinces. Crossing experiments among the 2 and 3 isolines
      representing 2 and 3 karyotypic forms of An. argyropus and An. pursati,
      respectively, indicated genetic compatibility in yielding viable progenies and
      synaptic salivary gland polytene chromosomes through F2-generations. The
      conspecific natures of these karyotypic forms in both species were further
      supported by very low intraspecific sequence variations (average genetic
      distance: An. argyropus = 0.003-0.007, An. pursati = 0-0.005) of ribosomal DNA
      (ITS2) and mitochondrial DNA (COI and COII). 

PMID- 25776590
TI  - Detection and characterization of viruses causing hand, foot and mouth disease
      from children in Seri Kembangan, Malaysia.
AB  - Hand, foot and mouth disease (HFMD) is a common viral infection among infants and
      children. The major causative agents of HFMD are enterovirus 71 (EV71) and
      coxsackievirus A16 (CVA16). Recently, coxsackievirus A6 (CVA6) infections were
      reported in neighboring countries. Infected infants and children may present with
      fever, mouth/throat ulcers, rashes and vesicles on hands and feet. Moreover, EV71
      infections might cause fatal neurological complications. Since 1997, EV71 caused
      fatalities in Sarawak and Peninsula Malaysia. The purpose of this study was to
      identify and classify the viruses which detected from the patients who presenting
      clinical signs and symptoms of HFMD in Seri Kembangan, Malaysia. From December
      2012 until July 2013, a total of 28 specimens were collected from patients with
      clinical case definitions of HFMD. The HFMD viruses were detected by using semi
      nested reverse transcription polymerase chain reaction (snRT-PCR). The positive
      snRT-PCR products were sequenced and phylogenetic analyses of the viruses were
      performed. 12 of 28 specimens (42.9%) were positive in snRT-PCR, seven are CVA6
      (58.3%), two CVA16 (16.7%) and three EV71 (25%). Based on phylogenetic analysis
      studies, EV71 strains were identified as sub-genotype B5; CVA16 strains
      classified into sub-genotype B2b and B2c; CVA6 strains closely related to strains
      in Taiwan and Japan. In this study, HFMD in Seri Kembangan were caused by
      different types of Enterovirus, which were EV71, CVA6 and CVA16. 

PMID- 25776591
TI  - DNA-based analyses of molds in Singapore public buildings results in a proposed
      Singapore Environmental Relative Moldiness Index.
AB  - Dust samples (n=75) were collected from shopping malls, hotels and libraries in
      Singapore and then analyzed using Mold Specific Quantitative Polymerase Chain
      Reaction (MSQPCR) for the 36 molds that make up the Environmental Relative
      Moldiness Index (ERMI). Most of these molds (23/36) occur at similar rates in
      Singapore and the United States. A Singapore Environmental Relative Moldiness
      Index (SERMI) is proposed which might be divided into low (<18), medium (18 to
      28) and high (>28) mold burden categories but more samples will help to refine
      these categories. 

PMID- 25776592
TI  - Bioassay and biochemical studies of the status of pirimiphos-methyl and
      cypermethrin resistance in Aedes (Stegomyia) aegypti and Aedes (Stegomyia)
      albopictus (Diptera: Culicidae) in Singapore.
AB  - Aedes (Stegomyia) aegypti (Linnaeus) and Ae. (Stegomyia) albopictus (Skuse) were
      sampled from five regions of Singapore (Central, North East, North West, South
      East and South West) and tested with diagnostic concentrations of the technical
      grade insecticides, pirimiphos-methyl and cypermethrin. Biochemical assays were
      performed on the same populations of Ae. aegypti and Ae. albopictus to determine
      activities of detoxifying enzymes, including non-specific esterase (EST),
      monooxygenase (MFO) and acetylcholinesterase (AChE). The diagnostic test showed
      that all Ae. aegypti populations were susceptible to pirimiphos-methyl (mortality
      = 99 to 100%), but resistant to cypermethrin (mortality = 11 to 76%). Resistance
      to pirimiphos-methyl was observed in all Ae. albopictus populations (mortality =
      49 to 74%) while cypermethrin resistance was detected in most Ae. albopictus
      populations (mortality = 40 to 75%), except those from Central (mortality = 86%)
      and South East (mortality = 94%) showing incipient resistance. The biochemical
      assays showed that there was significant enhancement (P < 0.001) of MFO activity
      in pyrethroid-resistant Ae. albopictus populations and most Ae. aegypti
      populations. The biochemical assay results suggested that AChE could play a role
      in pirimiphos-methyl resistance of Ae. albopictus in South West, South East and
      North East regions. The small but significant increase in EST activities in Ae.
      aegypti from all regions suggest that it may play a role in the observed
      cypermethrin resistance. 

PMID- 25776593
TI  - In vitro antibacterial activity of Quercus infectoria gall extracts against
      multidrug resistant bacteria.
AB  - Antimicrobial activities of plants have long been evaluated for their promising
      use as antimicrobial agent and in minimizing the unwanted resistance effects of
      microorganisms. The study was conducted to evaluate the antibacterial activity of
      Quercus infectoria gall crude extracts against multidrug resistant (MDR) bacteria
      in vitro. The screening test was determined by disc diffusion technique using
      sterile filter paper discs impregnated with 1 mg/ disc (50 mg/ml) aqueous and
      ethanol extracts of Q. infectoria galls tested on five selected MDR bacterial
      strains. The minimum inhibitory concentration (MIC) was determined using the
      twofold serial micro dilution technique at concentration ranging from 5.00 mg/ml
      to 0.01 mg/ml. The minimum bactericidal concentration (MBC) was determined by sub
      culturing the microtitre wells showing no turbidity on the agar plate to obtain
      the MBC value. Both extracts showed substantial inhibitory effects against
      methicillin resistant coagulase negative Staphylococcus (MRCoNS) and methicillin
      resistant Staphylococcus aureus (MRSA). A slightly reduced inhibitory zone
      diameter was observed with MDR Acinetobacter sp. while no inhibitory effect was
      displayed among the extended spectrum beta lactamases (ESBL) K. pneumoniae and
      ESBL E. coli isolates. A significant difference in the zone sizes between both
      extracts was only observed in MRSA (p < 0.05). The MIC values ranged from 0.08
      mg/ml to 0.63 mg/ml for aqueous and ethanol extracts against MRSA, MRCoNS and MDR
      Acinetobacter sp. while their MBC to MIC ratio values were 2 and less. The Q.
      infectoria gall extracts have shown very promising in vitro antibacterial
      activities and may be considered as a potentially good source of antimicrobial
      agent especially against MDR Gram positive bacteria. 

PMID- 25776594
TI  - Development and evaluation of a Multiplex Polymerase Chain Reaction for the
      detection of Salmonella species.
AB  - The present study aims to develop a system which consists of four pairs of
      primers that specifically detects Salmonella spp., Salmonella serovar Typhi and
      Salmonella serovar Paratyphi A with an internal amplification control. The
      system, when applied in Polymerase Chain Reaction (PCR) under specific
      conditions, reaction mixture and cycling temperatures produced four bands; 784
      bp, 496 bp, 332 bp and 187 bp. The DNA band 784 bp is present in all Salmonella
      spp., while the bands of 496 bp and 332 bp are only present in S. Paratyphi A and
      S. Typhi, respectively. An internal amplification control as indicated by the 187
      bp shows the system is working in optimum condition in all the tests. This
      multiplex PCR was evaluated on 241 bacterial cultures and 691 naturally
      contaminated samples. Overall, this multiplex PCR detection system provides a
      single step for simultaneous detection of DNAs of Salmonella spp., S. Typhi and
      S. Paratyphi A. 

PMID- 25776595
TI  - Possible association between recent migration and hospitalisation for dengue in
      an urban population: a prospective case-control study in northern Vietnam.
AB  - A prospective case-control study was conducted in urban districts in Hanoi,
      northern Vietnam to evaluate the effect of migration on the risk of
      hospitalisation for dengue in a Vietnamese urban population. We enrolled
      laboratory-confirmed dengue patients aged >= 18 years who were hospitalised in
      local hospitals in November and December 2010. Four neighbourhood-matched
      controls for each case were recruited within a week of hospitalisation.
      Sociodemographic data were collected by interviews, and the number of immature
      and adult mosquitoes within household premises was counted by entomological
      survey. Matched-pair analyses were conducted using conditional logistic
      regression models. Among 43 cases and 168 controls, 84% and 83% were migrants
      from rural areas, respectively. Although statistical significance was marginal,
      recent migration (residing in study area for <= 5 years) independently increased
      the risk of hospitalisation for dengue compared with inhabitants after
      controlling for potential confounders (adjusted odds ratio [aOR] = 3.78; 95%
      confidence interval [CI] = 0.99-14.27), whereas longer-term migration (residing
      in study area for >= 6 years) did not change the risk (aOR = 1.1; 95% CI = 0.30
      4.05). Younger age (18-34 years) (aOR = 7.26; 95% CI = 2.39-22.06) and higher
      adult Aedes aegypti infestation level within household premises (aOR = 9.25; 95%
      CI = 1.68-51.09) were also independently associated with hospitalisation for
      dengue. Recent migration from rural areas seems to increase the risk of
      hospitalisation for dengue in urban populations in endemic areas. Further
      research including cohort study should be done to confirm the impact of migration
      on the risk of dengue in urban areas. 

PMID- 25776596
TI  - A real-time loop-mediated isothermal amplification assay for rapid detection of
      Shigella species.
AB  - Shigellosis is a foodborne illness caused by the genus Shigella and is an
      important global health issue. The development of effective techniques for rapid
      detection of this pathogen is essential for breaking the chain of transmission.
      Therefore, we have developed a novel loop-mediated isothermal amplification
      (LAMP) assay targeting the invasion plasmid antigen H (ipaH) gene to rapidly
      detect Shigella species. This assay could be performed in 90 min at an optimal
      temperature of 64oC, with endpoint results visualized directly. Notably, the
      method was found to be more sensitive than conventional PCR. Indeed, the
      detection limit for the LAMP assay on pure bacterial cultures was 5.9 x 10(5)
      CFU/ml, while PCR displayed a limit of 5.9 x 10(7) CFU/ml. In spiked lettuce
      samples, the sensitivity of the LAMP assay was 3.6 x 10(4) CFU/g, whereas PCR was
      3.6 x 10(5) CFU/g. Overall, the assay accurately identified 32 Shigella spp. with
      one enteroinvasive Escherichia coli displaying positive reaction while the
      remaining 32 non-Shigella strains tested were negative. 

PMID- 25776597
TI  - Molecular detection of Entamoeba histolytica and Entamoeba dispar infection among
      wild rats in Kuala Lumpur, Malaysia.
AB  - Entamoeba histolytica infection is the third-greatest parasitic disease
      responsible for death in the world. Wild rats harbouring E. histolytica can be
      the possible reservoir hosts for human amoebiasis. There were numerous studies on
      prevalence of intestinal parasites among wild rats in Malaysia but none has
      reported E. histolytica. Rats were captured from Sentul and Chow Kit areas, Kuala
      Lumpur, Malaysia. The preserved stool samples were used for microscopy
      examination and molecular analysis. Out of 137 samples collected, 12 were
      positive for E. histolytica / E. dispar / E. moshkovskii microscopically. Two E.
      histolytica (1.4%), 1 E. dispar (0.7%) and 6 mixed infections of E. histolytica
      and E. dispar (4.3%) were detected using PCR. This is the first report of
      molecular detection of E. histolytica/dispar infection among wild rats in
      Malaysia. This study provides useful information about the potential risks of
      zoonotic agents and the importance of developing control measures to prevent
      zoonotic transmission. 

PMID- 25776598
TI  - Qualitative and quantitative assessment of Theileria annulata in cattle and
      buffaloes Polymerase Chain Reaction.
AB  - Bovine tropical theileriosis caused by Theileria annulata is a tick-borne disease
      associated with high morbidity and mortality in the livestock. The conventional
      method of diagnosis is by the demonstration of the parasite stages by microscopic
      examination. This method suffers from low sensitivity, making it even more
      difficult to detect piroplasms in the carriers. PCR based assays are known to be
      more sensitive. The present study was undertaken to detect and quantify T.
      annulata in the blood of clinically infected and carrier animals using a
      quantitative PCR protocol targeting the gene encoding the major merozoite
      piroplasm surface antigen Tams 1. A total of 116 samples were collected from
      infected as well as apparently healthy cattle and buffaloes. Of these, 74 samples
      (63.79%) were positive for T. annulata by real-time PCR, including the 15 samples
      that were positive by Giemsa staining. The parasite load ranged from 1.39 x 10(6)
      to 3.35 x 10(9) and 0.35 x 10(6) to 2.83 x 10(7) ml(-1) of blood in cattle and
      buffalo samples, respectively by qPCR. Our study suggests that real-time PCR
      assay can be used to detect and quantify the load of T. annulata in the blood of
      cattle and buffaloes. It also serves as a support to clinical diagnosis and
      assessment of carrier status in apparently healthy animals. 

PMID- 25776599
TI  - Predatory potential of Platynectes sp. (Coleoptera: Dytiscidae) on Aedes
      albopictus, the vector of dengue/chikungunya in Kerala, India.
AB  - Unused and discarded latex collection containers (LCCs) are the major breeding
      habitats of Aedes albopictus in the rubber plantations of Kerala, India.
      Platynectes sp. (Family: Dytiscidae) was observed to invade these habitats during
      the monsoon season and voraciously devour the larval instars of this major vector
      species of arbo-viral diseases. Field observations showed a reduction of 70.91%
      (p = 0.0017) and 100% in Aedes larval density, on the first and four days post
      release of eight beetles per LCC respectively. In laboratory, a beetle was found
      to devour 17.75 + 5.0 late larval instars of Ae. albopictus per day. Our findings
      indicate Platynectes sp. could be a potential bio-control agent against Ae.
      albopictus, the vector of chikungunya/dengue fevers, in rubber plantations. 

PMID- 25776600
TI  - Female black flies of Simulium (Diptera: Simuliidae) collected on humans in Tam
      Dao National Park, Vietnam: description of a new species and notes on four
      species newly recorded from Vietnam.
AB  - A total of 29 female black flies were captured by a hand net as they swarmed
      around humans in Tam Dao National Park, Vinh Phuc Province, Vietnam. They
      included one species of the subgenus Gomphostilbia (Simulium (Gomphostilbia)
      asakoae Takaoka & Davies) and five species of the subgenus Simulium, of which one
      species is described as Simulium (Simulium) vietnamense sp. nov. and the other
      four species (S. (S.) chungi Takaoka & Huang, S. (S.) grossifilum Takaoka &
      Davies, S. (S.) maenoi Takaoka & Choochote, and S. (S.) rufibasis Brunetti) are
      newly recorded from Vietnam.

PMID- 25776601
TI  - Evaluation of codon optimized recombinant Plasmodium knowlesi merozoite surface
      protein-119 (pkMSP-119) expressed in Pichia pastoris.
AB  - Malaria causes high global mortality and morbidity annually. Plasmodium knowlesi
      has been recognised as the fifth human Plasmodium sp. and its infection is widely
      distributed in Southeast Asia. Merozoite surface protein-119 (MSP-119) appears as
      a potential candidate for malaria blood stage vaccine as it could induce
      protective immunity. In this study, codon optimized P. knowlesi MSP-119 (pkMSP
      119) was expressed and purified in yeast Pichia pastoris expression system. The
      purified recombinant protein was further evaluated using Western blot assay using
      knowlesi malaria, non-knowlesi human malaria, non-malarial parasitic infections
      and healthy serum samples (n = 50). The sensitivity of purified pkMSP-119 towards
      detection of knowlesi infection was as 28.6% (2/7). pkMSP-119 did not react with
      all non-malarial parasitic infections and healthy donor sera, yet reacted with
      some non-knowlesi human malaria sera, therefore lead to a specificity of 86.0%
      (37/43). 

PMID- 25776602
TI  - Ontogenensis and developmental rate of the blow fly, Hypopygiopsis tumrasvini
      Kurahashi (Diptera: Calliphoridae).
AB  - Blow flies of the genus Hypopygiopsis are considered forensically important. In
      Thailand, four Hypopygiopsis species coexist, i.e., Hypopygiopsis fumipennis,
      Hypopygiopsis infumata, Hypopygiopsis violacea and Hypopygiopsis tumrasvini. In
      this study, the ontogeny and developmental rate of H. tumrasvini eggs, larvae and
      pupae were determined in the laboratory chamber reared at 25.0 +/- 2.0 degrees C
      and 80.0 +/- 5.0% RH. Larvae emerged from eggs 10-12 h after deposition. Mean
      length of the first, second, third (feeding phase), third (post-feeding phase)
      instars and puparia were 3.5 +/- 1.1, 7.2 +/- 1.1, 13.5 +/- 1.8, 12.5 +/- 0.5 and
      9.0 +/- 0.7 mm, respectively. The median development time for first, second,
      third instar (feeding phase), third instar (post-feeding phase) and pupariation
      period was 8 h, 10 h, 34 h, 22 d and 9-10 d, respectively. Developmental curve of
      the larval length indicated the rapid progression from 0 until 40 h from the
      first instar until the feeding third instar. Video recording of pupariation
      revealed the development of pupal respiratory horn beneath the larval integument
      at 27.0 h; whereas it protruded through the orifice of the integument at 27.5 h.

PMID- 25776603
TI  - Molecular survey and sequence analysis of Anaplasma spp. in cattle and ticks in a
      Malaysian farm.
AB  - This study was conducted to determine the occurrence of Anaplasma spp. in the
      blood samples of cattle, goats, deer and ticks in a Malaysian farm. Using
      polymerase chain reaction (PCR) and sequencing approach, Anaplasma spp. was
      detected from 81(84.4%) of 96 cattle blood samples. All blood samples from 23
      goats and 22 deer tested were negative. Based on the analysis of the Anaplasma
      partial 16S ribosomal RNA gene, four sequence types (genotypes 1 to 4) were
      identified in this study. Genotypes 1-3 showed high sequence similarity to those
      of Anaplasma platys/ Anaplasma phagocytophilum, whilst genotype 4 was identical
      to those of Anaplasma marginale/ Anaplasma centrale/ Anaplasma ovis. Anaplasma
      DNA was detected from six (5.5%) of 109 ticks which were identified as
      Rhipicephalus (formely known as Boophilus) microplus ticks collected from the
      cattle. This study reported for the first time the detection of four Anaplasma
      sequence types circulating in the cattle population in a farm in Malaysia. The
      detection of Anaplasma DNA in R. microplus ticks in this study provides evidence
      that the ticks are one of the potential vectors for transmission of anaplasmosis
      in the cattle. 

PMID- 25776604
TI  - Seroprevalence of IgG and IgM antibodies and associated risk factors for
      toxoplasmosis in cats and dogs from sub-tropical arid parts of Pakistan.
AB  - Pet cats and dogs are an important source of human toxoplasmosis because of their
      intimate relationship with humans. Present study was designed to determine the
      prevalence and risk factors of toxoplasmosis in cats and dogs in northern sub
      tropical arid region of Pakistan where no such work has been previously
      conducted. For this study 420 cats and 408 dogs visiting different pet clinics
      and veterinary hospitals were screened for the presence of anti-Toxoplasma IgG
      and IgM antibodies using ELISA technique. Epidemiological information regarding
      age, sex, area, outdoor access and hunting practice was obtained from the owners
      by questionnaire interview. Overall seroprevalence in cats and dogs was 26.43%
      (111/420) and 28.43% (116/408) respectively. IgG antibodies were found in 23.33%
      (98) cats and 25.49% (104) dogs while IgM antibodies were found in 3.57% (15)
      cats and 3.92% (16) dogs. Seroprevalence was significantly high in cats and dogs
      older than one year. No significant difference was recorded between males and
      females. Cats and dogs from rural areas showed higher prevalence. Dogs which had
      access to outside also showed high seroprevalence. The present study indicates
      that Toxoplasma gondii is widespread in pet animals in Pakistan which may have
      important implication for public health. 

PMID- 25776605
TI  - Effects of preservatives and killing methods on morphological features of a
      forensic fly, Chrysomya megacephala (Fabricius, 1794) larva.
AB  - Preservation of larvae retrieved from cadavers is important in ensuring the
      quality and integrity of entomological specimens used for the estimation of post
      mortem interval (PMI). The process of killing and preserving larvae could distort
      the larvae leading to inaccurate estimation of PMI. In this study, the effects of
      killing Chrysomya megacephala larvae with hot water at different temperatures and
      subsequent maintenance in various preservatives were determined. Larvae not
      killed by hot water but preserved directly were used as control. The types of
      preservative used were 10% formalin, 70% ethanol and Kahle's solution. The
      morphological features examined were length, turgidity, curvature and coloration
      of larvae. Larvae killed in 80oC hot water have shorter mean length (12.47 +/-
      2.86 mm) compared to those in 60oC hot water (12.95 +/- 2.69 mm). Increasing the
      duration of preservation in all types of preservative caused elongations of
      larvae treated or untreated with hot water. There were no significant changes in
      larval turgidity preserved in Kahle's solution compared to other two
      preservatives and were unaffected by the duration of storage. Larvae preserved in
      Kahle's solution experienced the least changes in coloration and shape compared
      to other preserved larvae in 70% ethanol or 10% formalin. Larvae directly
      immersed alive in 70% ethanol experienced the most changes in curvature,
      coloration and turgidity. This study suggested that killing larvae with hot water
      at 80oC and preservation in Kahle's solution is the optimum method resulting in
      least changes in morphological features of Ch. megacephala larvae.

PMID- 25776606
TI  - Construction and heterologous expression of a truncated Haemagglutinin (HA)
      protein from the avian influenza virus H5N1 in Escherichia coli.
AB  - Malaysia first reported H5N1 poultry case in 2004 and subsequently outbreak in
      poultry population in 2007. Here, a recombinant gene encoding of peptide
      epitopes, consisting fragments of HA1, HA2 and a polybasic cleavage site of H5N1
      strain Malaysia, was amplified and cloned into pET-47b(+) bacterial expression
      vector. DNA sequencing and alignment analysis confirmed that the gene had no
      alteration and in-frame to the vector. Then, His-tagged truncated HA protein was
      expressed in Escherichia coli BL21 (DE3) under 1 mM IPTG induction. The protein
      expression was optimized under a time-course induction study and further purified
      using Ni-NTA agarose under reducing condition. Migration size of protein was
      detected at 15 kDa by Western blot using anti-His tag monoclonal antibody and
      demonstrated no discrepancy compared to its calculated molecular weight. 

PMID- 25776607
TI  - Investigation on the conA binding properties of Klebsiella pneumoniae.
AB  - Klebsiella pneumoniae is a healthcare-associated bacterial pathogen which causes
      severe diseases in immunocompromised individuals. Concanavalin A (conA), a lectin
      which recognizes proteins with mannose or glucose residues, has been reported to
      agglutinate K. pneumoniae and hence, is postulated to have therapeutical
      potential for K. pneumoniae-induced liver infection. This study investigated the
      conA binding properties of a large collection of clinical isolates of K.
      pneumoniae. ConA agglutination reaction was demonstrated by 94 (51.4%) of 183 K.
      pneumoniae isolates using a microtiter plate assay. The conA agglutination
      reactions were inhibited in the presence of 2.5 mg/ml D-mannose and 2.5 mg/ml
      glucose, and following pretreatment of the bacterial suspension with protease and
      heating at 80oC. Majority of the positive isolates originated from respiratory
      specimens. Isolation of conA-binding proteins from K. pneumoniae ATCC 700603
      strain was performed using conA affinity column and the conA binding property of
      the eluted proteins was confirmed by western blotting analysis using conA-HRP
      conjugates. Proteins with molecular weights ranging from 35 to 60 kDa were eluted
      from the conA affinity column, of which four were identified as outer membrane
      protein precursor A (37 kDa), outer membrane protein precursor C (40 kDa),
      enolase (45 kDa) and chaperonin (60 kDa) using mass spectrometry analysis.
      Several conA binding proteins (including 45 and 60 kDa) were found to be
      immunogenic when reacted with rabbit anti-Klebsiella antibody. The function and
      interplay of the conA binding proteins in bacterium-host cell relationship merits
      further investigation. 

PMID- 25776608
TI  - Morphological and protein analyses of adult female salivary glands of Anopheles
      barbirostris species A1 (Diptera: Culicidae).
AB  - Morphology and protein profiles of female salivary glands of Anopheles
      barbirostris species A1 were analyzed. Female glands consisted of a distinctive
      tri-lobed structure connected to a main salivary canal, a single medial and two
      lateral lobes with proximal and distal portions. Cellular architecture was
      similar among the lobes, with secretory material appearing as large masses. Cells
      of the proximal-lateral lobes contained secretory masses with a finely
      filamentous aspect. In the distal-lateral lobes, cells had a dense secretory
      product with mottled pattern. Cells of the medial lobe had secretory masses which
      were uniformly stained and highly electron dense. Following emergence, the glands
      accumulated secretory material rapidly and developed completely within three
      days. Degenerative changes including loss of stored secretion and increase of
      cytoplasmic vacuolation and concentric lamellar structures were observed from day
      16 post emergence that correlated with total amount of the salivary gland
      proteins determined during development. SDS-PAGE, nanoLC-MS, and glycoprotein
      analysis revealed at least eleven major protein bands, of which each
      morphological region contained different major proteins. Two glycoproteins,
      apyrase/5'-nucleotidase and D7, were identified. These results form a basis for
      further studies on details of cytopathological changes of malarial infected
      glands and roles of the proteins in disease transmission. 

PMID- 25776609
TI  - Sexual differentiation and developmental stage identification of the Indian
      cockroach, Pycnoscelus indicus (Blattodea: Blaberidae).
AB  - We found that sexual differentiation of all the nymphal stages of Pycnoscelus
      indicus (Fabricius) was possible by observing the developmental features of their
      posterior abdominal segments. Using this observation, the sex of even the 1(st)
      stage instar nymph could be determined. The female of the 1(st) to 6(th) stage
      instar nymph possess a V-shaped notch at the middle of the posterior edge of the
      9(th) sternite. This notch is not seen in the male nymph. In the female 7(th)
      stage (final stage) instar nymph, the styli were not apparent and, the 8(th) and
      9(th) sternites became degenerated and were covered over by the profoundly
      developed 7(th) sternite. In contrast, all stages of the male nymph showed the
      presence of styli. Thus, it is possible to differentiate the sex of all the
      stages, from 1(st) to 7(th), of the nymph of P. indicus taxonomically. Moreover,
      it is also possible to identify the various specimens as to which stage the
      nymphal instar belong to, by counting the number of cercal segments from the
      ventral view. 

PMID- 25776610
TI  - Current status of parasitic infections among Pangkor Island community in
      Peninsular Malaysia.
AB  - Limited data is available on the prevalence of parasitic infections among the
      island communities in Malaysia with most studies performed between 1960s-1980s.
      This study was conducted to determine the current prevalence status of parasitic
      infections among communities living in Pangkor Island Peninsular Malaysia. A
      total of 131 stool and 298 serum samples were collected and subjected to
      microscopic examination for intestinal protozoa and helminths and detection of
      Toxoplasma gondii antibodies using commercial ELISA kits respectively. In
      addition, thin and thick peripheral blood films were microscopically screened for
      the presence of Plasmodium spp. and microfilariae respectively. The overall
      prevalence of intestinal parasitic infections among Pangkor Island community was
      9.9% (13/131) with T. trichiura (5.3%) being the most common intestinal parasite
      detected. Toxoplasmosis was reported in almost 60% of the community with the
      seroprevalence being significantly high among females (64.7%) compared to males
      (52.8%) (p=0.038). None of those examined samples were infected with intestinal
      sarcocystosis, malaria and filariasis. This study revealed that the prevalence of
      intestinal parasitic infections among Pangkor Island community has been greatly
      reduced compared to that reported 35 years ago. Massive improvements in the
      socioeconomic status, personal hygiene, water facilities and sanitation may have
      contributed to the low prevalence of parasitic infections in this community.
      Nevertheless, further studies still need to be performed to determine the
      possible risk factors for the high prevalence of toxoplasmosis in this community.

PMID- 25776611
TI  - Thelazia rhodesii infection on cattle in Kupang district.
AB  - A cross-sectional study was carried out to determine the prevalence, the
      intensity, infection, clinical sign, to identify species and to investigate
      associated risk factors of thelaziosis in cattle in Kupang district, Nusa
      Tenggara Timur Province. A total of 385 head of cattle were randomly selected
      from 96 farms in three subdistricts of Kupang District and observed for
      thelaziosis. The nematode present in the eye of cattle were collected with a
      forcep after administering local anesthesia (10% Xylocaine). The potential risk
      factors related to age of cattle, human resources and farm management were
      obtained by interviewing the farmers. Logistic regression was applied to analyze
      related risk factor of thelaziosis. The result showed that of the total 385
      cattle observed, 23 (5.96%) were infected by Thelazia spp., of which 22 cattle
      showed apparent clinical signs namely excessive lacrimation and conjunctivitis
      that led to keratoconjunctivitis, while one cattle showed ulceration. A total of
      357 worms (157 males and 210 female) were collected from 23 infected cattle with
      the mean number of worms in infected cattle being 32.92 +/- 21.03. Observations
      on morphological characteristics using Scanning Electron Microscope (SEM) helped
      to identify the nematode species as Thelazia rhodesii. The infection was more
      prevalent in older cattle (>= 6-12 month old) than calves (0-6 month old)
      (P<0.05). Significant risk factors of animal husbandry practices affecting the
      prevalence of thelaziosis in cattle were anthelmintic treatment, grazing
      management, barn cleaning, and manure management. Our results highlight that
      significant risk factors of the disease should be considered in designing
      strategic control programs for thelaziosis. 

PMID- 25776612
TI  - Seroepidemiology of leptospirosis in dogs and rats in Trinidad.
AB  - Stray dogs (n=207), suspected canine cases of leptospirosis (n=50) and rats
      (n=200) from the Caribbean island of Trinidad were subjected to the Microscopic
      Agglutination Test (MAT) for leptospirosis. The seroprevalence in stray dogs was
      15.5% (n=32), the predominant serogroup was Icterohaemorrhagiae (14.5%; n=30)
      with agglutinations to serovars Copenhageni at 5.8%, Icterohaemorrhagiae at 4.8%,
      Mankarso at 3.9%. The seroprevalence among suspected canine cases was 72% (n=36)
      with Icterohaemorrhagiae again being the predominant serogroup at 60% inclusive
      of serovars: Copenhageni, 44%; Mankarso, 14%; and Icterohaemorrhagiae 2%. A
      seroprevalence of 16.5% was determined in rats, all agglutinations were to the
      Icterohaemorrhagiae serogroup (inclusive of serovars Copenhageni, 9.5%;
      Icterohaemorrhagiae, 5.5%; and Mankarso, 1.5%). Overall serovar Copenhageni was
      the most common serovar as 11.6% of all the animal species tested by the MAT were
      positive and may be an important zoonotic serovar in Trinidad. The titres of
      infecting serovars of Leptospira in suspected canine cases of leptospirosis were
      considerably higher than that found in stray dogs and in rats where the lowest
      titres were found. Age and sex were not significant risk factors except in the
      case of rats where age was significant, indicating that juvenile rats were at a
      significantly higher risk. There was no definite pattern of the distribution of
      positive animals or the serovars when using the MAT. Data obtained in the current
      study indicate that dogs and rats in Trinidad have the potential to be sources of
      leptospiral infections for humans. This potential has public health implications
      making it imperative to control rat and stray dog populations in the island to
      reduce the risk of human leptospirosis. 

PMID- 25776613
TI  - Survey and genetic variation of Spirometra erinaceieuropaei sparganum in frogs
      and snakes from Guangxi of southern China.
AB  - The prevalence of sparganum infection in wild frogs (Rana rugulosa and R.
      temporaria) and snakes (Enhydris chinensis) was investigated in Guangxi Zhuang
      Autonomous Region of Southern China from June 2013 to August 2013. The results
      showed that 30.37% (65/214) of the caught wild frogs and 50% (3/6) of examined
      snakes were found to be infected with plerocercoids (spargana) of the genus
      Spirometra. To investigate the genetic variation of the collected spargana, three
      mitochondrial DNA (mtDNA) regions, namely cytochrome c oxidase subunit 1 and 3
      (cox1 and cox3), NADH dehydrogenase subunits 4 (nad4) were amplified, sequenced,
      and analyzed. The sequences of cox1, cox3 and pnad4 are 444, 387 and 585 bp in
      length, respectively. The base composition of cox1, cox3 and pnad4 were generally
      AT rich with a mean of 62.7%, 67.2% and 64.9%, respectively. Phylogenetic
      analyses using Bayesian inference (BI) and maximum parsimony (MP) indicated that
      all the Spirometra sparganum isolates in Guangxi represented S. erinaceieuropaei.

PMID- 25776614
TI  - Growth profile and SEM analyses of Candida albicans and Escherichia coli with
      Hymenocallis littoralis (Jacq.) Salisb leaf extract.
AB  - Hymenocallis littoralis (Jacq.) Salisb (Melong kecil) commonly known as 'Spider
      Lily' is an herbaceous plant from the family Amaryllidaceae. Study was carried
      out to determine the effect of H. littoralis leaf extract on the growth and
      morphogenesis of two pathogenic microbes, Candida albicans and Escherichia coli.
      The leaf extract displayed favourable anticandidal and antibacterial activity
      with a minimum inhibition concentration (MIC) of 6.25 mg/mL. Time kill study
      showed both microbes were completely killed after treated with leaf extract at 20
      h. Both microbes' cell walls were heavily ruptured based on scanning electron
      microscopy (SEM) analysis. The significant anticandidal and antibacterial
      activities showed by H. littoralis leaf extract suggested the potential
      antimicrobial agent against C. albicans and E. coli. 

PMID- 25776615
TI  - Pharmacokinetics, bioavailability and PK/PD relationship of cefquinome for
      Escherichia coli in Beagle dogs.
AB  - The pharmacokinetics and bioavailability of cefquinome in Beagle dogs were
      determined by intravenous (IV), intramuscular (IM) or subcutaneous (SC) injection
      at a single dose of 2 mg/kg body weight (BW). The minimum inhibitory
      concentrations (MIC) of cefquinome against 217 Escherichia coli isolated from
      dogs were also investigated. After IV injection, the plasma concentration-time
      curve of cefquinome was analyzed using a two-compartmental model, and the mean
      values of t1/2alpha (h), t1/2beta (h), Vss (L/kg), ClB (L/kg/h) and AUC
      (MUg.h/mL) were 0.12, 0.98, 0.30, 0.24 and 8.51, respectively. After IM and SC
      administration, the PK data were best described by a one-compartmental model with
      first-order absorption. The mean values of t1/2Kel , t1/2Ka , tmax (h), Cmax
      (MUg/mL) and AUC (MUg.h/mL) were corresponding 0.85, 0.14, 0.43, 4.83 and 8.24
      for IM administration, 0.99, 0.29, 0.72, 3.88 and 9.13 for SC injection. The
      duration of time that drug levels exceed the MIC (%T > MIC) were calculated using
      the determined MIC90 (0.125 MUg/mL) and the PK data obtained in this study. The
      results indicated that the dosage regimen of cefquinome at 2 mg/kg BW with 12-h
      intervals could achieve %T > MIC above 50% that generally produced a satisfactory
      bactericidal effect against E. coli isolated from dogs in this study. 

PMID- 25776656
TI  - Screening, diagnosis and management of congenital hypothyroidism: European
      Society for Paediatric Endocrinology Consensus Guideline.

PMID- 25776657
TI  - PS48 can replace bovine serum albumin in pig embryo culture medium, and improve
      in vitro embryo development by phosphorylating AKT.
AB  - The application of embryo-related technology is dependent on in vitro culture
      systems. Unfortunately, most culture media are suboptimal and result in
      developmentally compromised embryos. Since embryo development is partially
      dependent upon Warburg Effect-like metabolism, our goal was to test the response
      of embryos treated with compounds that are known to stimulate or enhance this
      Effect. One such compound is 5-(4-chloro-phenyl)-3-phenyl-pent-2-enoic acid
      (PS48). When added during oocyte maturation, the quality of the resultant embryos
      was compromised, whereas when added to the culture medium after fertilization,
      PS48 improved both the percentage of embryos that reach the blastocyst stage and
      the number of nuclei in those blastocysts. Embryonic PS48 treatment resulted in
      more phosphorylated v-akt murine thymoma viral oncogene homolog (AKT) in
      blastocyst-stage embryos as compared to the controls. Further, PS48 could replace
      bovine serum albumin in embryo culture medium, as demonstrated by high-quality
      embryos that were developmentally competent. The action of PS48 appears to be via
      stimulation of phosphoinositide-3 kinase and phosphorylation of AKT, which is
      consistent with stimulation of the Warburg Effect.

PMID- 25776658
TI  - A new hydronaphthalenone from the mangrove-derived Daldinia eschscholtzii PSU
      STD57.
AB  - One new hydronaphthalenone derivative (1) was isolated from the broth extract of
      the endophytic fungus Daldinia eschscholtzii PSU-STD57 together with five known
      compounds, isosclerone (2), 8-methoxy-1-naphthol, 1,8-dimethoxynaphthalene, 2,6
      dihydroxyphenyl-1-butan-1-one and tyrosol. The structures were assigned by
      spectroscopic methods. All the compounds were tested for antimicrobial activity
      against Staphylococcus aureus, methicillin-resistant S. aureus and Microsporum
      gypseum. 

PMID- 25776727
TI  - Prediction and diagnosis of post transplant diabetes.
AB  - The identification of at-risk individuals prior to transplantation may enable
      implementation of measures to prevent or delay PTDM development, while early
      detection facilitates prompt management and may prevent acute and chronic
      complications. Thus, in this review, we examine proposed tools for the prediction
      of PTDM for use prior to and following solid organ transplantation. This includes
      PTDM prediction models based on biochemical assessments of glycaemia and other
      indices, in addition to those solely based on clinical parameters. We also
      examine the available methods for diagnosis of PTDM early and late post
      transplant, including the advantages and limitations of fasting plasma glucose
      (FPG), OGTT, random plasma glucose and HbA1c assessment. Key findings are that
      OGTT should remain the gold standard diagnostic method for PTDM, however, there
      is emerging data to support a role for HbA1c beyond 3 months posttransplant. FPG
      has low sensitivity during the first year post-transplant. Improved prediction
      and diagnosis of PTDM may lead to improvements in patient survival, quality of
      life and health care costs in future.

PMID- 25776728
TI  - Low-temperature liquid precursors of crystalline metal oxides assisted by
      heterogeneous photocatalysis.
AB  - The photocatalytically assisted decomposition of liquid precursors of metal
      oxides incorporating TiO2 particles enables the preparation of functional layers
      from the ferroelectric Pb(Zr,Ti)O3 and multiferroic BiFeO3 perovskite systems at
      temperatures not exceeding 350 oC. This enables direct deposition on flexible
      plastic, where the multifunctionality provided by these complex-oxide materials
      guarantees their potential use in next-generation flexible electronics.

PMID- 25776729
TI  - Validation of a HPLC-ESI MS/MS method for the determination of clonidine in human
      plasma and its application in a bioequivalence study in Chinese healthy
      volunteers.
AB  - A rapid and sensitive liquid chromatography-tandem mass spectrometry (HPLC-MS/MS)
      method to determine clonidine in human plasma was developed and fully validated.
      Sample preparation was involved an one-step extraction with diethyl ether.
      Donepezil was employed as the internal standard (IS). Chromatographic separation
      was performed on a Hypersil BDS C18 column (i.d. 2.1 * 50 mm, particle size 3MUm)
      with a mobile phase of methanol-water (containing 0.1% formic acid; 60:40, v/v)
      at a flow rate of 200 MUL/min. The peaks were detected by mass spectrometry using
      the electrospray ion source in selected reaction monitoring mode. The extraction
      recovery was 72.53-85.25%. The method was found to be linear in a concentration
      range of 0.02-6.00 ng/mL and the lower limit of quantification was 0.02 ng/mL.
      The within- and between-batch precisions at three concentrations were 4.33-16.47
      and 7.24-17.24% with accuracies of -2.47-10.91 and 1.86-10.19%, respectively.
      This validated method was successfully used for a bioequivalence study of two
      clonidine transdermal patches on healthy volunteers. The results suggested that
      the test formulation of clonidine patch met the regulatory criterion for
      bioequivalence to the reference formulation, but a larger sample size should be
      needed for the estimation of bioequivalence.

PMID- 25776730
TI  - Association of facilitated glucose transporter 2 gene variants with the
      myelomeningocele phenotype.
AB  - BACKGROUND: Neural tube defects (NTDs) remain the second most common cause of
      congenital malformations. Myelomeningocele (MM), the most common NTD compatible
      with survival, results from genetic and environmental factors. Epidemiologic
      studies and murine models support the hypotheses that obesity, diabetes and
      hyperglycemia confer increased risk of NTDs. Presence of wild-type facilitated
      glucose transporter, Glut2, in mouse embryos has been shown to increase risk for
      NTDs in hyperglycemic pregnancy. METHODS: The GLUT2 gene of 96 MM patients was
      amplified, sequenced and compared with the reference sequence (NM_000340).
      Variants previously unreported in the single nucleotide polymorphisms (SNP)
      database were considered novel. Allele frequencies of reported SNPs were compared
      with reference populations using Fisher's exact test. RESULTS: Analysis revealed
      three novel variants: a substitution in the core promoter region (c.-331c>t), a
      substitution (c.-182g>a) in the 5'-untranslated region, and a single base pair
      deletion (c.1441delT) in the coding sequences. Polymorphic alleles for 10 SNPs
      were also identified. Seven SNPs are significantly associated with MM in the
      Mexican American patients tested (p < 0.05) and two of the seven remained
      significant after Bonferroni correction. CONCLUSION: We identified three novel
      variants and seven SNPs associated with MM. The novel variants in the core
      promoter and in the 5'-untranslated region could affect GLUT2 mRNA transcription
      and stability and translation efficiency. The c.1441delT variant is predicted to
      alter the reading frame and prematurely terminate translation of the GLUT2
      protein at the C-terminus, affecting GLUT2 protein function. Presence of GLUT2
      variants may disrupt GLUT2 activity and influence MM susceptibility.

PMID- 25776733
TI  - Reply to Eliezer M. Van Allen, Levi A. Garraway and Jonathan E. Rosenberg's
      Letter to the Editor re: Floris H. Groenendijk, Jeroen de Jong, Elisabeth E.
      Fransen van de Putte, et al. ERBB2 Mutations Characterize a Subgroup of Muscle
      invasive Bladder Cancers with Excellent Response to Neoadjuvant Chemotherapy. Eur
      Urol. In press. http://dx.doi.org/10.1016/j.eururo.2015.01.014.

PMID- 25776731
TI  - Distinctions between diagnostic and classification criteria?

PMID- 25776734
TI  - Barriers in access to home care services among ethnic minority and Dutch elderly-
      a qualitative study.
AB  - BACKGROUND: Ethnic minority elderly have a high prevalence of functional
      limitations and chronic conditions compared to Dutch elderly. However, their use
      of home care services is low compared to Dutch elderly. OBJECTIVES: Explore the
      barriers to access to home care services for Turkish, Moroccan Surinamese and
      ethnic Dutch elderly. DESIGN: Qualitative semi-structured group interviews and
      individual interviews. SETTING: The Netherlands. PARTICIPANTS: Seven group
      interviews (n=50) followed by individual interviews (n=5) were conducted, in the
      preferred language of the participants. METHODS: Results were ordered and
      reported according to a framework of access to health care services. This
      framework describes five dimensions of accessibility to generate access to health
      care services, from the perspective of the users: ability to perceive health
      needs, ability to seek health care, ability to reach, ability to pay and ability
      to engage. RESULTS: This study shows that while barriers are common among all
      groups, several specific barriers in access to home care services exist for
      ethnic minority elderly. Language and communication barriers as well as limited
      networks and a preference for informal care seem to mutually enforce each other,
      resulting in many barriers during the navigation process to home care.
      CONCLUSION: In order to provide equal access to home care for all who need it,
      the language and communication barriers should be tackled by home care services
      and home care nurses.

PMID- 25776736
TI  - Staff perceptions of a Productive Community Services implementation: A
      qualitative interview study.
AB  - BACKGROUND: The Productive Series is a collection of change programmes designed
      by the English National Health Service (NHS) Institute for Innovation and
      Improvement to help frontline healthcare staff improve quality and reduce wasted
      time, so that this time can be reinvested into time spent with patients. The
      programmes have been implemented in at least 14 countries around the world. This
      study examines an implementation of the Productive Community Services programme
      that took place in a Community healthcare organisation in England from July 2010
      to March 2012. OBJECTIVES: To explore staff members' perceptions of a Productive
      Community Services implementation. DESIGN: Cross-sectional interview. SETTINGS:
      Community Healthcare Organisation in East Anglia, England. PARTICIPANTS: 45
      participants were recruited using purposive, snowballing and opportunistic
      sampling methods to represent five main types of staff group in the organisation;
      clinical team members, administrative team members, service managers/team
      leaders, senior managers and software support staff. Team members were recruited
      on the basis that they had submitted data for at least one Productive Community
      Services module. METHODS: Semi-structured individual and group interviews were
      carried out after the programme concluded and analysed using thematic analysis.
      RESULTS: This report focuses on six of the themes identified. The analysis found
      that communication was not always effective, and there was a lack of awareness,
      knowledge and understanding of the programme. Many staff did not find the
      Productive Community Services work relevant, and although certain improvements
      were sustained, suboptimal practices crept back. Although negative outcomes were
      reported, such as the programme taking time away from patients initially, many
      benefits were described including improved stock control and work environments,
      and better use of the Electronic Patient Record system. CONCLUSIONS: One of the
      themes identified highlighted the positive perceptions of the programme, however
      a focus on five other themes indicate that important aspects of the
      implementation could have been improved. The innovation and implementation
      literature already addresses the issues identified, which suggests a gap between
      theory and practice for implementation teams. A lack of perceived relevance also
      suggests that similar programmes need to be made more easily adaptable for the
      varied specialisms found in Community Services. Further research on Productive
      Community Services implementations and knowledge transfer is required, and
      publication of studies focusing on the less positive aspects of implementations
      may accelerate this process.

PMID- 25776735
TI  - The association between physical dependency and the presence of neuropsychiatric
      symptoms, with the admission of people with dementia to a long-term care
      institution: a prospective observational cohort study.
AB  - BACKGROUND: Dementia is a progressive neurological disorder that causes a high
      degree of dependency. This dependency has been defined as an increased need for
      assistance due to deterioration in cognition and physical functioning, and
      changes in behavior. Highly dependent people with dementia are more likely to be
      institutionalized. OBJECTIVES: To investigate the association between specific
      categories of physical dependency and the presence of neuropsychiatric symptoms
      in people with dementia admitted to a long-term care institution. DESIGN: A
      prospective observational cohort study. SETTINGS: Home care and long-term care
      institutions in eight European countries. PARTICIPANTS: People with dementia
      living at home but at risk of institutionalization and recently institutionalized
      people with dementia. METHOD: Baseline and 3-month follow-up interviews were
      performed between November, 2010 and April, 2012. The sample consisted of 116
      recently institutionalized dementia sufferers and 949 people with dementia still
      living at home. Physical dependency was measured using the Katz Activity of Daily
      Living index, and neuropsychiatric symptoms were assessed through The
      Neuropsychiatric Inventory. Specific categories of dependency were analyzed by
      performing a logistic regression analysis. This followed examination of baseline
      characteristics to define the degree of physical dependency, as factors
      associated with institutionalization, and evaluation of the same characteristics
      at 3-month follow-up to detect changes in the degree of physical dependency and
      neuropsychiatric symptoms associated with recent admission to a long-term care
      institution. RESULTS: Toileting, dressing and continence dependency was higher in
      institutionalized people than in those receiving home-care. Delusion,
      hallucination, agitation, anxiety, apathy, motor-disturbances, night-time
      behavior and eating disorders were also worse in the institutionalized. Logistic
      regression analysis showed that independent factors significantly associated with
      being recently institutionalized were toileting (odds ratio=2.3; 95% confidence
      interval=1.43-3.71) and motor disturbances (odds ratio=1.81; 95% confidence
      interval=1.15-2.87). CONCLUSIONS: This study supports the association between
      type and degree of physical dependency in people with dementia and long-term
      institutionalization. Institutionalization is associated with physical dependency
      and the presence of neuropsychiatric symptoms.

PMID- 25776737
TI  - Oral films: Current status and future perspectives II - Intellectual property,
      technologies and market needs.

PMID- 25776738
TI  - Polymeric micelles and nanoemulsions as tumor-targeted drug carriers: Insight
      through intravital imaging.
AB  - Intravital imaging of nanoparticle extravasation and tumor accumulation has
      revealed, for the first time, detailed features of carrier and drug behavior in
      circulation and tissue that suggest new directions for optimization of drug
      nanocarriers. Using intravital fluorescent microscopy, the extent of the
      extravasation, diffusion in the tissue, internalization by tissue cells, and
      uptake by the RES system were studied for polymeric micelles, nanoemulsions, and
      nanoemulsion-encapsulated drug. Discrimination of vascular and tissue
      compartments in the processes of micelle and nanodroplet extravasation and tissue
      accumulation was possible. A simple 1-D continuum model was suggested that
      allowed discriminating between various kinetic regimes of nanocarrier (or
      released drug) internalization in tumors of various sizes and cell density. The
      extravasation and tumor cell internalization occurred much faster for polymeric
      micelles than for nanoemulsion droplets. Fast micelle internalization resulted in
      the formation of a perivascular fluorescent coating around blood vessels. A new
      mechanism of micelle extravasation and internalization was suggested, based on
      the fast extravasation and internalization rates of copolymer unimers while
      maintaining micelle/unimer equilibrium in the circulation. The data suggested
      that to be therapeutically effective, nanoparticles with high internalization
      rate should manifest fast diffusion in the tumor tissue in order to avoid
      generation of concentration gradients that induce drug resistance. However an
      extra-fast diffusion should be avoided as it may result in the flow of
      extravasated nanoparticles from the tumor to normal organs, which would
      compromise targeting efficiency. The extravasation kinetics were different for
      nanodroplets and nanodroplet-encapsulated drug F-PTX suggesting a premature
      release of some fraction of the drug from the carrier. In conclusion, the
      development of an "ideal" drug carrier should involve the optimization of both
      drug retention and carrier diffusion parameters. 

PMID- 25776739
TI  - In Vivo Performance of Moderately Crosslinked, Thermally Treated Polyethylene in
      a Prospective Randomized Controlled Primary Total Knee Arthroplasty Trial.
AB  - Cross-linked bearings have been developed for use in total knee arthroplasty that
      exhibit improved wear properties, but at the expense of a decrease in mechanical
      strength of the cross-linked material. Adoption has been slow due to fears of
      mechanical failure secondary to this alteration in mechanical properties. This
      prospective, randomized study compared mid-term survivorship, clinical and
      radiographic results of a conventional polyethylene (GVF) to a cross-linked
      polyethylene (XLK) in total knee prostheses of the same design. At minimum 5-year
      follow-up there was no difference in survivorship, clinical performance or
      radiographic findings between the groups. There were no revisions for
      polyethylene wear, osteolysis or tibial insert dissociation. Most importantly,
      there were no revisions for mechanical failure or fracture of the polyethylene
      bearing in either group. 

PMID- 25776740
TI  - Experimental analysis and modeling of ultrasound assisted freezing of potato
      spheres.
AB  - In recent years, innovative methods such as ultrasound assisted freezing have
      been developed in order to improve the freezing process. During freezing of
      foods, accurate prediction of the temperature distribution, phase ratios, and
      process time is very important. In the present study, ultrasound assisted
      immersion freezing process (in 1:1 ethylene glycol-water solution at 253.15K) of
      potato spheres (0.02 m diameter) was evaluated using experimental, numerical and
      analytical approaches. Ultrasound (25 kHz, 890 W m(-2)) was irradiated for
      different duty cycles (DCs=0-100%). A finite volume based enthalpy method was
      used in the numerical model, based on which temperature and liquid fraction
      profiles were simulated by a program developed using OpenFOAM(r) CFD software. An
      analytical technique was also employed to calculate freezing times. The results
      showed that ultrasound irradiation could decrease the characteristic freezing
      time of potatoes. Since ultrasound irradiation increased the heat transfer
      coefficient but simultaneously generated heat at the surface of the samples, an
      optimum DC was needed for the shortest freezing time which occurred in the range
      of 30-70% DC. DCs higher than 70% increased the freezing time. DCs lower than 30%
      did not provide significant effects on the freezing time compared to the control
      sample. The numerical model predicted the characteristic freezing time in
      accordance with the experimental results. In addition, analytical calculation of
      characteristic freezing time exhibited qualitative agreement with the
      experimental results. As the numerical simulations provided profiles of
      temperature and water fraction within potatoes frozen with or without ultrasound,
      the models can be used to study and control different operation situations, and
      to improve the understanding of the freezing process.

PMID- 25776741
TI  - Binaural interaction in human auditory brainstem response compared for tone-pips
      and rectangular clicks under conditions of auditory and visual attention.
AB  - Binaural interaction in the auditory brainstem response (ABR) represents the
      discrepancy between the binaural waveform and the sum of monaural ones. A typical
      ABR binaural interaction in humans is a reduction of the binaural amplitude
      compared to the monaural sum at the wave-V latency, i.e., the DN1 component. It
      has been considered that the DN1 is mainly elicited by high frequency components
      of stimuli whereas some studies have shown the contribution of low-to-middle
      frequency components to the DN1. To examine this issue, the present study
      compared the ABR binaural interaction elicited by tone pips (1 kHz, 10-ms
      duration) with the one by clicks (a rectangular wave, 0.1-ms duration) presented
      at 80 dB peak equivalent SPL and a fixed stimulus onset interval (180 ms). The
      DN1 due to tone pips was vulnerable compared to the click-evoked DN1. The pip
      evoked DN1 was significantly detected under auditory attention whereas it failed
      to reach significance under visual attention. The click-evoked DN1 was robustly
      present for the two attention conditions. The current results might confirm the
      high frequency sound contribution to the DN1 elicitation.

PMID- 25776742
TI  - High-field fMRI reveals tonotopically-organized and core auditory cortex in the
      cat.
AB  - As frequency is one of the most basic elements of sound, it is not surprising
      that the earliest stages of auditory cortical processing are tonotopically
      organized. In cats, there are four known tonotopically organized cortical areas:
      the anterior (AAF), posterior (PAF), and ventral posterior (VPAF) auditory fields
      and primary auditory cortex (A1). Electrophysiological and anatomical evidence
      have suggested that AAF and A1 form core auditory cortex. The purpose of this
      investigation was to determine if high-field functional magnetic resonance
      imaging (fMRI) could be used to define the borders of all four tonotopically
      organized areas, identify core auditory cortex, and demonstrate tonotopy similar
      to that found using more invasive techniques. Five adult cats were examined.
      Eight different pure tones or one broad-band noise (BBN) stimuli were presented
      in a block paradigm during continuous fMRI scanning. Analysis was performed on
      each animal individually using conservative familywise error thresholds. Group
      analysis was performed by extracting data from fMRI analysis software and
      performing a battery of statistical tests. In auditory cortex, a reversal of the
      tonotopic gradient is known to occur at the borders between tonotopically
      organized areas. Therefore, high and low tones were used to delineate these
      borders. Activations in response to BBN as opposed to tonal stimulation
      demonstrated that core auditory cortex consists of both A1 and AAF. Finally,
      tonotopy was identified in each of the four known tonotopically organized areas.
      Therefore, we conclude that fMRI is effective at defining all four tonotopically
      organized cortical areas and delineating core auditory cortex. 

PMID- 25776743
TI  - Exposure to hazardous substances in Cathode Ray Tube (CRT) recycling sites in
      France.
AB  - The Waste Electrical and Electronic Equipment (WEEE) or e-waste recycling sector
      has grown considerably in the last fifteen years due to the ever shorter life
      cycles of consumables and an increasingly restrictive policy context. Cathode Ray
      Tubes (CRTs) from used television and computer screens represent one of the main
      sources of e-waste. CRTs contain toxic materials such as lead, cadmium, barium,
      and fluorescent powders which can be released if recycling of CRTs is not
      appropriate. Exposure to these harmful substances was assessed in nine workshops
      where CRT screens are treated. Particulate exposure levels were measured using a
      gravimetric method and metals were analysed by plasma emission spectrometry. The
      maximum levels of worker exposure were 8.8mg/m(3), 1504.3MUg/m(3), 434.9MUg/m(3),
      576.3MUg/m(3) and 2894.3MUg/m(3) respectively for inhalable dust, barium,
      cadmium, lead and yttrium. The maximum levels of airborne pollutants in static
      samples were 39.0mg/m(3), 848.2MUg/m(3), 698.4MUg/m(3), 549.3MUg/m(3) and
      3437.9MUg/m(3) for inhalable dust, barium, cadmium, lead and yttrium. The most
      harmful operations were identified, and preventive measures for reducing the
      chemical risk associated with screen recycling were proposed. Workplace
      measurements were used to define recommendations for reducing the chemical risks
      in CRT screens recycling facilities and for promoting the design and development
      of "clean and safe" processes in emerging recycling channels. 

PMID- 25776744
TI  - The omentum is a site of protective IgM production during intracellular bacterial
      infection.
AB  - Infection of mice with the bacterium Ehrlichia muris elicits a protective T cell
      independent (TI) IgM response mediated primarily by a population of CD11c
      expressing plasmablasts in the spleen. Although splenic marginal zone (MZ) B
      cells are considered to be important for TI responses to blood-borne pathogens,
      MZ B cells were not responsible for generating plasmablasts in response to
      Ehrlichia muris. Moreover, antigen-specific serum IgM was decreased only modestly
      in splenectomized mice and in mice that lacked spleen, lymph nodes, and Peyer's
      patches (SLP mice). Both splenectomized and SLP mice were protected against
      lethal ehrlichial challenge infection. Moreover, we found a high frequency of
      Ehrlichia-specific plasmablasts in the omentum of both conventional and SLP mice.
      Omental plasmablasts elicited during Ehrlichia infection lacked expression of
      CD138 but expressed CD11c in a manner similar to that of their splenic
      counterparts. Selective ablation of CD11c-expressing B cells nearly eliminated
      the omental Ehrlichia-specific plasmablasts and reduced antigen-specific serum
      IgM, identifying the omental B cells as a source of IgM production in the SLP
      mice. Generation of the omental plasmablasts was route dependent, as they were
      detected following peritoneal infection but not following intravenous infection.
      Our data identify the omentum as an important auxiliary site of IgM production
      during intracellular bacterial infection. 

PMID- 25776745
TI  - Nonreplicating, cyst-defective type II Toxoplasma gondii vaccine strains
      stimulate protective immunity against acute and chronic infection.
AB  - Live attenuated vaccine strains, such as type I nonreplicating uracil auxotroph
      mutants, are highly effective in eliciting lifelong immunity to virulent acute
      infection by Toxoplasma gondii. However, it is currently unknown whether vaccine
      elicited immunity can provide protection against acute infection and also prevent
      chronic infection. To address this problem, we developed nonreverting,
      nonreplicating, live attenuated uracil auxotroph vaccine strains in the type II
      Deltaku80 genetic background by targeting the deletion of the orotidine 5'
      monophosphate decarboxylase (OMPDC) and uridine phosphorylase (UP) genes.
      Deletion of OMPDC induced a severe uracil auxotrophy with loss of replication,
      loss of virulence in mice, and loss of the ability to develop cysts and chronic
      infection. Vaccination of mice using type II Deltaku80 Deltaompdc mutants
      stimulated a fully protective CD8(+) T cell-dependent immunity that prevented
      acute infection by type I and type II strains of T. gondii, and this vaccination
      also severely reduced or prevented cyst formation after type II challenge
      infection. Nonreverting, nonreplicating, and non-cyst-forming Deltaompdc mutants
      provide new tools to examine protective immune responses elicited by vaccination
      with a live attenuated type II vaccine. 

PMID- 25776746
TI  - Avoidance of autophagy mediated by PlcA or ActA is required for Listeria
      monocytogenes growth in macrophages.
AB  - Listeria monocytogenes is a facultative intracellular pathogen that escapes from
      phagosomes and grows in the cytosol of infected host cells. Most of the
      determinants that govern its intracellular life cycle are controlled by the
      transcription factor PrfA, including the pore-forming cytolysin listeriolysin O
      (LLO), two phospholipases C (PlcA and PlcB), and ActA. We constructed a strain
      that lacked PrfA but expressed LLO from a PrfA-independent promoter, thereby
      allowing the bacteria to gain access to the host cytosol. This strain did not
      grow efficiently in wild-type macrophages but grew normally in macrophages that
      lacked ATG5, a component of the autophagy LC3 conjugation system. This strain
      colocalized more with the autophagy marker LC3 (42% +/- 7%) at 2 h postinfection,
      which constituted a 5-fold increase over the colocalization exhibited by the wild
      type strain (8% +/- 6%). While mutants lacking the PrfA-dependent virulence
      factor PlcA, PlcB, or ActA grew normally, a double mutant lacking both PlcA and
      ActA failed to grow in wild-type macrophages and colocalized more with LC3 (38%
      +/- 5%). Coexpression of LLO and PlcA in a PrfA-negative strain was sufficient to
      restore intracellular growth and decrease the colocalization of the bacteria with
      LC3. In a cell-free assay, purified PlcA protein blocked LC3 lipidation, a key
      step in early autophagosome biogenesis, presumably by preventing the formation of
      phosphatidylinositol 3-phosphate (PI3P). The results of this study showed that
      avoidance of autophagy by L. monocytogenes primarily involves PlcA and ActA and
      that either one of these factors must be present for L. monocytogenes growth in
      macrophages. 

PMID- 25776747
TI  - A genomic virulence reference map of Enterococcus faecalis reveals an important
      contribution of phage03-like elements in nosocomial genetic lineages to
      pathogenicity in a Caenorhabditis elegans infection model.
AB  - In the present study, the commensal and pathogenic host-microbe interaction of
      Enterococcus faecalis was explored using a Caenorhabditis elegans model system.
      The virulence of 28 E. faecalis isolates representing 24 multilocus sequence
      types (MLSTs), including human commensal and clinical isolates as well as
      isolates from animals and of insect origin, was investigated using C. elegans
      strain glp-4 (bn2ts); sek-1 (km4). This revealed that 6 E. faecalis isolates
      behaved in a commensal manner with no nematocidal effect, while the remaining
      strains showed a time to 50% lethality ranging from 47 to 120 h. Principal
      component analysis showed that the difference in nematocidal activity explained
      94% of the variance in the data. Assessment of known virulence traits revealed
      that gelatinase and cytolysin production accounted for 40.8% and 36.5% of the
      observed pathogenicity, respectively. However, coproduction of gelatinase and
      cytolysin did not increase virulence additively, accounting for 50.6% of the
      pathogenicity and therefore indicating a significant (26.7%) saturation effect.
      We employed a comparative genomic analysis approach using the 28 isolates
      comprising a collection of 82,356 annotated coding sequences (CDS) to identify
      2,325 patterns of presence or absence among the investigated strains. Univariate
      statistical analysis of variance (ANOVA) established that individual patterns
      positively correlated (n = 61) with virulence. The patterns were investigated to
      identify potential new virulence traits, among which we found five patterns
      consisting of the phage03-like gene clusters. Strains harboring phage03 showed,
      on average, 17% higher killing of C. elegans (P = 4.4e(-6)). The phage03 gene
      cluster was also present in gelatinase-and-cytolysin-negative strain E. faecalis
      JH2-2. Deletion of this phage element from the JH2-2 clinical strain rendered the
      mutant apathogenic in C. elegans, and a similar mutant of the nosocomial V583
      isolate showed significantly attenuated virulence. Bioinformatics investigation
      indicated that, unlike other E. faecalis virulence traits, phage03-like elements
      were found at a higher frequency among nosocomial isolates. In conclusion, our
      report provides a valuable virulence map that explains enhancement in E. faecalis
      virulence and contributes to a deeper comprehension of the genetic mechanism
      leading to the transition from commensalism to a pathogenic lifestyle. 

PMID- 25776748
TI  - Targeting surface protein SasX by active and passive vaccination to reduce
      Staphylococcus aureus colonization and infection.
AB  - SasX is a recently described surface protein of Staphylococcus aureus that is
      linked to the epidemic success of hospital-associated methicillin-resistant
      clones, in particular in Asia. It enhances nasal colonization and virulence in
      skin and lung infection models. Here, we evaluated the potential of SasX as a
      vaccine component in passive and active immunization efforts using mouse
      infection models. We found that SasX induced a specific immune response
      predominantly based on IgG1 antibodies. Active immunization with recombinant SasX
      or passive immunization with rabbit polyclonal anti-SasX IgG significantly
      decreased the size of lesions caused by S. aureus in a skin infection model.
      Furthermore, active immunization reduced acute lung injury in a lung infection
      model. Moreover, active or passive immunization significantly reduced S. aureus
      colonization in a nasal colonization model. Finally, anti-SasX IgG enhanced the
      susceptibility of S. aureus to killing by human neutrophils. We conclude that
      SasX is a potential target for therapeutics or vaccines designed to moderate
      colonization and infection by sasX-positive epidemic strains of S. aureus. 

PMID- 25776749
TI  - Impact of malaria preexposure on antiparasite cellular and humoral immune
      responses after controlled human malaria infection.
AB  - To understand the effect of previous malaria exposure on antiparasite immune
      responses is important for developing successful immunization strategies.
      Controlled human malaria infections (CHMIs) using cryopreserved Plasmodium
      falciparum sporozoites provide a unique opportunity to study differences in
      acquisition or recall of antimalaria immune responses in individuals from
      different transmission settings and genetic backgrounds. In this study, we
      compared antiparasite humoral and cellular immune responses in two cohorts of
      malaria-naive Dutch volunteers and Tanzanians from an area of low malarial
      endemicity, who were subjected to the identical CHMI protocol by intradermal
      injection of P. falciparum sporozoites. Samples from both trials were analyzed in
      parallel in a single center to ensure direct comparability of immunological
      outcomes. Within the Tanzanian cohort, we distinguished one group with moderate
      levels of preexisting antibodies to asexual P. falciparum lysate and another
      that, based on P. falciparum serology, resembled the malaria-naive Dutch cohort.
      Positive P. falciparum serology at baseline was associated with a lower parasite
      density at first detection by quantitative PCR (qPCR) after CHMI than that for
      Tanzanian volunteers with negative serology. Post-CHMI, both Tanzanian groups
      showed a stronger increase in anti-P. falciparum antibody titers than Dutch
      volunteers, indicating similar levels of B-cell memory independent of serology.
      In contrast to the Dutch, Tanzanians failed to increase P. falciparum-specific in
      vitro recall gamma interferon (IFN-gamma) production after CHMI, and innate IFN
      gamma responses were lower in P. falciparum lysate-seropositive individuals than
      in seronegative individuals. In conclusion, positive P. falciparum lysate
      serology can be used to identify individuals with better parasite control but
      weaker IFN-gamma responses in circulating lymphocytes, which may help to stratify
      volunteers in future CHMI trials in areas where malaria is endemic. 

PMID- 25776750
TI  - Colony morphology variation of Burkholderia pseudomallei is associated with
      antigenic variation and O-polysaccharide modification.
AB  - Burkholderia pseudomallei is a CDC tier 1 select agent that causes melioidosis, a
      severe disease in humans and animals. Persistent infections are common, and there
      is currently no vaccine available. Lipopolysaccharide (LPS) is a potential
      vaccine candidate. B. pseudomallei expresses three serologically distinct LPS
      types. The predominant O-polysaccharide (OPS) is an unbranched heteropolymer with
      repeating d-glucose and 6-deoxy-l-talose residues in which the 6-deoxy-l-talose
      residues are variably replaced with O-acetyl and O-methyl modifications. We
      observed that primary clinical B. pseudomallei isolates with mucoid and nonmucoid
      colony morphologies from the same sample expressed different antigenic types
      distinguishable using an LPS-specific monoclonal antibody (MAb). MAb-reactive
      (nonmucoid) and nonreactive (mucoid) strains from the same patient exhibited
      identical LPS banding patterns by silver staining and indistinguishable
      genotypes. We hypothesized that LPS antigenic variation reflected modification of
      the OPS moieties. Mutagenesis of three genes involved in LPS synthesis was
      performed in B. pseudomallei K96243. Loss of MAb reactivity was observed in both
      wbiA (encoding a 2-O-acetyltransferase) and wbiD (putative methyl transferase)
      mutants. The structural characteristics of the OPS moieties from isogenic
      nonmucoid strain 4095a and mucoid strain 4095c were further investigated.
      Utilizing nuclear magnetic resonance (NMR) spectroscopy, we found that B.
      pseudomallei 4095a and 4095c OPS antigens exhibited substitution patterns that
      differed from the prototypic OPS structure. Specifically, 4095a lacked 4-O
      acetylation, while 4095c lacked both 4-O-acetylation and 2-O-methylation. Our
      studies indicate that B. pseudomallei OPS undergoes antigenic variation and
      suggest that the 9D5 MAb recognizes a conformational epitope that is influenced
      by both O-acetyl and O-methyl substitution patterns. 

PMID- 25776751
TI  - Activated human valvular interstitial cells sustain interleukin-17 production to
      recruit neutrophils in infective endocarditis.
AB  - The mechanisms that underlie valvular inflammation in streptococcus-induced
      infective endocarditis (IE) remain unclear. We previously demonstrated that
      streptococcal glucosyltransferases (GTFs) can activate human heart valvular
      interstitial cells (VIC) to secrete interleukin-6 (IL-6), a cytokine involved in
      T helper 17 (Th17) cell differentiation. Here, we tested the hypothesis that
      activated VIC can enhance neutrophil infiltration through sustained IL-17
      production, leading to valvular damage. To monitor cytokine and chemokine
      production, leukocyte recruitment, and the induction or expansion of CD4(+)
      CD45RA(-) CD25(-) CCR6(+) Th17 cells, primary human VIC were cultured in vitro
      and activated by GTFs. Serum cytokine levels were measured using an enzyme-linked
      immunosorbent assay (ELISA), and neutrophils and Th17 cells were detected by
      immunohistochemistry in infected valves from patients with IE. The expression of
      IL-21, IL-23, IL-17, and retinoic acid receptor-related orphan receptor C (Rorc)
      was upregulated in GTF-activated VIC, which may enhance the proliferation of
      memory Th17 cells in an IL-6-dependent manner. Many chemokines, including
      chemokine (C-X-C motif) ligand 1 (CXCL1), were upregulated in GTF-activated VIC,
      which might recruit neutrophils and CD4(+) T cells. Moreover, CXCL1 production in
      VIC was induced in a dose-dependent manner by IL-17 to enhance neutrophil
      chemotaxis. CXCL1-expressing VIC and infiltrating neutrophils could be detected
      in infected valves, and serum concentrations of IL-17, IL-21, and IL-23 were
      increased in patients with IE compared to healthy donors. Furthermore, elevated
      serum IL-21 levels have been significantly associated with severe valvular
      damage, including rupture of chordae tendineae, in IE patients. Our findings
      suggest that VIC are activated by bacterial modulins to recruit neutrophils and
      that such activities might be further enhanced by the production of Th17
      associated cytokines. Together, these factors can amplify the release of
      neutrophilic contents in situ, which might lead to severe valvular damage.

PMID- 25776752
TI  - Molecular dissection of a Borrelia burgdorferi in vivo essential purine transport
      system.
AB  - The Lyme disease spirochete Borrelia burgdorferi is dependent on purine salvage
      from the host environment for survival. The genes bbb22 and bbb23 encode purine
      permeases that are essential for B. burgdorferi mouse infectivity. We now
      demonstrate the unique contributions of each of these genes to purine transport
      and murine infection. The affinities of spirochetes carrying bbb22 alone for
      hypoxanthine and adenine were similar to those of spirochetes carrying both
      genes. Spirochetes carrying bbb22 alone were able to achieve wild-type levels of
      adenine saturation but not hypoxanthine saturation, suggesting that maximal
      hypoxanthine uptake requires the presence of bbb23. Moreover, the purine
      transport activity conferred by bbb22 was dependent on an additional distal
      transcriptional start site located within the bbb23 open reading frame. The
      initial rates of uptake of hypoxanthine and adenine by spirochetes carrying bbb23
      alone were below the level of detection. However, these spirochetes demonstrated
      a measurable increase in hypoxanthine uptake over a 30-min time course. Our
      findings indicate that bbb22-dependent adenine transport is essential for B.
      burgdorferi survival in mice. The bbb23 gene was dispensable for B. burgdorferi
      mouse infectivity, yet its presence was required along with that of bbb22 for B.
      burgdorferi to achieve maximal spirochete loads in infected mouse tissues. These
      data demonstrate that both genes, bbb22 and bbb23, are critical for B.
      burgdorferi to achieve wild-type infection of mice and that the differences in
      the capabilities of the two transporters may reflect distinct purine salvage
      needs that the spirochete encounters throughout its natural infectious cycle.

PMID- 25776753
TI  - Correlates between models of virulence for Mycobacterium tuberculosis among
      isolates of the Central Asian lineage: a case for lysozyme resistance testing?
AB  - Virulence factors (VFs) contribute to the emergence of new human Mycobacterium
      tuberculosis strains, are lineage dependent, and are relevant to the development
      of M. tuberculosis drugs/vaccines. VFs were sought within M. tuberculosis lineage
      3, which has the Central Asian (CAS) spoligotype. Three isolates were selected
      from clusters previously identified as dominant in London, United Kingdom. Strain
      associated virulence was studied in guinea pig, monocyte-derived macrophage, and
      lysozyme resistance assays. Whole-genome sequencing, single nucleotide
      polymorphism (SNP) analysis, and a literature review contributed to the
      identification of SNPs of interest. The animal model revealed borderline
      differences in strain-associated pathogenicity. Ex vivo, isolate C72 exhibited
      statistically significant differences in intracellular growth relative to C6 and
      C14. SNP candidates inducing lower fitness levels included 123 unique
      nonsynonymous SNPs, including three located in genes (lysX, caeA, and ponA2)
      previously identified as VFs in the laboratory-adapted reference strain H37Rv and
      shown to confer lysozyme resistance. C72 growth was most affected by lysozyme in
      vitro. A BLAST search revealed that all three SNPs of interest (C35F, P76Q, and
      P780R) also occurred in Tiruvallur, India, and in Uganda. Unlike C72, however, no
      single isolate identified through BLAST carried all three SNPs simultaneously.
      CAS isolates representative of three medium-sized human clusters demonstrated
      differential outcomes in models commonly used to estimate strain-associated
      virulence, supporting the idea that virulence varies within, not just across, M.
      tuberculosis lineages. Three VF SNPs of interest were identified in two
      additional locations worldwide, which suggested independent selection and
      supported a role for these SNPs in virulence. The relevance of lysozyme
      resistance to strain virulence remains to be established.

PMID- 25776754
TI  - Toll-like receptor 2-dependent extracellular signal-regulated kinase signaling in
      Mycobacterium tuberculosis-infected macrophages drives anti-inflammatory
      responses and inhibits Th1 polarization of responding T cells.
AB  - Mycobacterium tuberculosis survives within macrophages and employs immune evasion
      mechanisms to persist in the host. Protective T helper type 1 (Th1) responses are
      induced, and the immune response in most individuals is sufficient to restrict M.
      tuberculosis to latent infection, but most infections are not completely
      resolved. As T cells and macrophages respond, a balance is established between
      protective Th1-associated and other proinflammatory cytokines, such as
      interleukin-12 (IL-12), interferon gamma (IFN-gamma), and tumor necrosis factor
      alpha, and anti-inflammatory cytokines, such as IL-10. The mechanisms by which M.
      tuberculosis modulates host responses to promote its survival remain unclear. In
      these studies, we demonstrate that M. tuberculosis induction of IL-10,
      suppression of IL-12, and inhibition of class II major histocompatibility complex
      (MHC-II) molecules in infected macrophages are all driven by Toll-like receptor 2
      (TLR2)-dependent activation of the extracellular signal-regulated kinases (ERK).
      Elimination of ERK signaling downstream of TLR2 by pharmacologic inhibition with
      U0126 or genetic deletion of Tpl2 blocks IL-10 secretion and enhances IL-12 p70
      secretion. We demonstrate that M. tuberculosis regulation of these pathways in
      macrophages affects T cell responses to infected macrophages. Thus, genetic
      blockade of the ERK pathway in Tpl2(-/-) macrophages enhances Th1 polarization
      and IFN-gamma production by antigen-specific CD4(+) T cells responding to M.
      tuberculosis infection. These data indicate that M. tuberculosis and its potent
      TLR2 ligands activate ERK signaling in macrophages to promote anti-inflammatory
      macrophage responses and blunt Th1 responses against the pathogen.

PMID- 25776755
TI  - Characterization of CPAF critical residues and secretion during Chlamydia
      trachomatis infection.
AB  - CPAF (chlamydial protease-like activity factor), a Chlamydia serine protease, is
      activated via proximity-induced intermolecular dimerization that triggers
      processing and removal of an inhibitory peptide occupying the CPAF substrate
      binding groove. An active CPAF is a homodimer of two identical intramolecular
      heterodimers, each consisting of 29-kDa N-terminal and 35-kDa C-terminal
      fragments. However, critical residues for CPAF intermolecular dimerization,
      catalytic activity, and processing were defined in cell-free systems.
      Complementation of a CPAF-deficient chlamydial organism with a plasmid-encoded
      CPAF has enabled us to characterize CPAF during infection. The transformants
      expressing CPAF mutated at intermolecular dimerization, catalytic, or cleavage
      residues still produced active CPAF, although at a lower efficiency, indicating
      that CPAF can tolerate more mutations inside Chlamydia-infected cells than in
      cell-free systems. Only by simultaneously mutating both intermolecular
      dimerization and catalytic residues was CPAF activation completely blocked during
      infection, both indicating the importance of the critical residues identified in
      the cell-free systems and exploring the limit of CPAF's tolerance for mutations
      in the intracellular environment. We further found that active CPAF was always
      detected in the host cell cytoplasm while nonactive CPAF was restricted to within
      the chlamydial inclusions, regardless of how the infected cell samples were
      treated. Thus, CPAF translocation into the host cell cytoplasm correlates with
      CPAF enzymatic activity and is not altered by sample treatment conditions. These
      observations have provided new evidence for CPAF activation and translocation,
      which should encourage continued investigation of CPAF in chlamydial
      pathogenesis.

PMID- 25776757
TI  - Erratum to: Sustained Benefit at 2 Years for Covered Stents Versus Bare-Metal
      Stents in Long SFA Lesions: The VIASTAR Trial.

PMID- 25776756
TI  - Evaluation of the efficiency of human immune system reconstitution in NSG mice
      and NSG mice containing a human HLA.A2 transgene using hematopoietic stem cells
      purified from different sources.
AB  - Severely immunodeficient mice such as the NOD/SCID/IL2rgamma(null) (NSG) strain
      can be engrafted with human hematopoietic stem cells (HSCs), resulting in
      chimeric mice containing many components of the human immune system (Human Immune
      System mice or HIS mice). HIS mice can both support the replication of and
      recapitulate much of the immunological response to a variety of pathogens,
      including ones with strict human tropism, such as HIV-1. In an effort to develop
      a better mouse model for human infectious pathogen infection and possible immune
      resolution, we compared the human immune system reconstitution of NSG mice
      following injection with human CD34(+) HSCs purified from either fetal liver (FL)
      or umbilical cord blood (UCB). We analyzed reconstitution in standard NSG mice as
      well as a derivative of these mice containing an HLA.A2 encoding transgene
      (NSG.A2). HSCs from both sources effectively reconstituted hematopoietic lineages
      when injected into NSG mice. In marked contrast, total CD45(+) human
      hematopoietic cells in NSG.A2 mice were well reconstituted by HSCs from UCB but
      very poorly by HSCs purified from FL. Moreover, the reconstitution of T cell
      lineages in NSG.A2 mice by HSCs from UCB was inferior to that obtained using NSG
      mice. We also found that FL CD34(+) HSCs contain a much higher percentage of
      cells with a phenotype consistent with primitive progenitors than UCB HSCs. We
      discuss possible explanations for the influence of the HLA.A2 transgene on
      hematopoietic reconstitution using the two sources of HSCs. 

PMID- 25776758
TI  - Molecular characterization of Pvr9 that confers a hypersensitive response to
      Pepper mottle virus (a potyvirus) in Nicotiana benthamiana.
AB  - There are some R genes against potyviruses which were mapped in pepper. However,
      none of them has been characterized at the molecular level. In this study, we
      characterized Pvr9 which is an Rpi-blb2 ortholog from pepper and confers a
      hypersensitive response to Pepper mottle virus (PepMoV) in a transient expression
      system in Nicotiana benthamiana. This gene putatively encoded for 1298 amino
      acids and is located on pepper chromosome 6. PepMoV NIb was the elicitor of the
      Pvr9-mediated hypersensitive response. NIb from several other potyviruses also
      elicited the hypersensitive response. Inoculation of pepper with PepMoV resulted
      in a minor increase in Pvr9 transcription in the resistant cultivar CM334 and a
      slight down-regulation in the susceptible cultivar Floral Gem. The 5' upstream
      region of Pvr9 from cultivar CM334 had higher transcription activity than the
      region from cultivar Floral Gem. The cultivars CM334 and Floral Gem had non
      functional Pvr9 homologs with loss-of-function mutations. 

PMID- 25776760
TI  - Pathogenesis of novel reassortant avian influenza virus A (H5N8) Isolates in the
      ferret.
AB  - Outbreaks of avian influenza virus H5N8 first occurred in 2014, and spread to
      poultry farms in Korea. Although there was no report of human infection by this
      subtype, it has the potential to threaten human public health. Therefore, we
      evaluated the pathogenesis of H5N8 viruses in ferrets. Two representative Korean
      H5N8 strains did not induce mortality and significant respiratory signs after an
      intranasal challenge in ferrets. However, ferrets intratracheally infected with
      A/broiler duck/Korea/Buan2/2014 virus showed dose-dependent mortality. Although
      the Korean H5N8 strains were classified as the HPAI virus, possessing multiple
      basic amino acids in the cleavage site of the hemagglutinin sequence, they did
      not produce pathogenesis in ferrets challenged intranasally, similar to the
      natural infection route. These results could be useful for public health by
      providing the pathogenic characterization of H5N8 viruses. 

PMID- 25776759
TI  - Small particle aerosol inoculation of cowpox Brighton Red in rhesus monkeys
      results in a severe respiratory disease.
AB  - Cowpox virus (CPXV) inoculation of nonhuman primates (NHPs) has been suggested as
      an alternate model for smallpox (Kramski et al., 2010, PLoS One, 5, e10412).
      Previously, we have demonstrated that intrabronchial inoculation of CPXV-Brighton
      Red (CPXV-BR) into cynomolgus monkeys resulted in a disease that shared many
      similarities to smallpox; however, severe respiratory tract disease was observed
      (Smith et al., 2011, J. Gen. Virol.). Here we describe the course of disease
      after small particle aerosol exposure of rhesus monkeys using computed tomography
      (CT) to monitor respiratory disease progression. Subjects developed a severe
      respiratory disease that was uniformly lethal at 5.7 log10 PFU of CPXV-BR. CT
      indicated changes in lung architecture that correlated with changes in peripheral
      blood monocytes and peripheral oxygen saturation. While the small particle
      aerosol inoculation route does not accurately mimic human smallpox, the data
      suggest that CT can be used as a tool to monitor real-time disease progression
      for evaluation of animal models for human diseases. 

PMID- 25776762
TI  - A downside of diversity? A response to Gallagher et al.

PMID- 25776761
TI  - IFI44 suppresses HIV-1 LTR promoter activity and facilitates its latency.
AB  - IFI44 is an interferon-alfa inducible protein, and is associated with infection
      of several viruses. However, IFI44 elicits minimal antiviral effects on these
      viruses, and its exact role is still unknown. Here we show that IFI44 inhibits
      HIV-1 replication in vitro. Through depletion of endogenous IFI44 or
      overexpression of IFI44 we confirm that IFI44 suppresses HIV-1 LTR promoter
      activity and affects viral transcription. Furthermore, we find that IFI44
      localizes to nuclei and binds to the HIV-1 LTR promoter in HIV-1 infected cells.
      Removing suppression of HIV-1 transcription benefits reactivation of HIV-1
      proviruses for purging latent reservoirs. We demonstrate that depletion of
      endogenous IFI44 in J-LAT cells induces reactivation of latent HIV-1. Based on
      these results, we propose a model in which IFI44 is recruited to the HIV-1 LTR,
      which may suppress viral transcription and prevent reactivation of latent HIV-1.
      Our study suggests a previously unrecognized anti-HIV phenomenon for interferon
      stimulated proteins. 

PMID- 25776763
TI  - [Immunotherapies and melanoma].
AB  - Metastatic melanoma treatment has been radically modified over the last four
      years with the emergence of new and effective therapeutic strategies targeted
      anti-BRAF therapies as well as immunotherapy. Following this latter immunotherapy
      strategy, anti-CTLA4 antibody ipilimumab demonstrated a benefit in terms of
      overall survival in patients with metastatic melanoma and is now challenged by
      other checkpoint inhibitors, antibodies directed against PD-1 and PD-L1 that have
      extremely promising benefit/risk ratio. Adverse events as well as evaluation
      criteria are different from the ones associated with classical chemotherapy or
      targeted therapies. The challenge for the next years will be to optimize these
      new strategies, by possibly using these new drugs sequentially or in combination
      for a higher clinical benefit for our patients. 

PMID- 25776765
TI  - [Recent evolutions in metastatic melanoma].

PMID- 25776764
TI  - [Targeted molecular therapies (except immunotherapy)].
AB  - Metastatic melanoma has been a very poor prognostic cancer with a median of
      survival between six to eight months. A lot of new therapies have been discovered
      these last years. Two types of treatment have emerged: immunotherapy and targeted
      therapy. Targeted therapies have been developed because of the discovery of new
      oncogenic mutations with a big impact of melanoma development. The efficacy is
      great with a high overall response and a good tolerance. However, most of
      patients escape in few months of targeted therapy. The sequence of drug using and
      their combination are the question for the next years. 

PMID- 25776766
TI  - [Molecular alterations in melanoma and targeted therapies].
AB  - Melanoma is a skin cancer whose incidence is increasing steadily. The recent
      discovery of frequent and recurrent genetic alterations in cutaneous melanoma
      allowed a molecular classification of tumors into distinct subgroups, and paved
      the way for targeted therapy. Several signaling pathways are involved in the
      progression of this disease with oncogenic mutations affecting signaling
      pathways: MAPK, PI3K, cAMP and cyclin D1/CDK4. In each of these pathways, several
      potential therapeutic targets have been identified and specific inhibitors have
      already been developed and have shown clinical efficacy. The use of these
      inhibitors is often conditioned by tumors genotyping. In France, melanomas
      genotyping is supported by the platforms of the National Cancer Institute (INCA),
      which implemented a national program ensuring access to innovation for
      personalized medicine. The identification of new targets in melanoma supplies a
      very active dynamic development of innovative molecules contributing to changing
      the therapeutic landscape of this pathology. 

PMID- 25776767
TI  - An Efficient Approach for Automated Mass Segmentation and Classification in
      Mammograms.
AB  - Breast cancer is becoming a leading death of women all over the world; clinical
      experiments demonstrate that early detection and accurate diagnosis can increase
      the potential of treatment. In order to improve the breast cancer diagnosis
      precision, this paper presents a novel automated segmentation and classification
      method for mammograms. We conduct the experiment on both DDSM database and MIAS
      database, firstly extract the region of interests (ROIs) with chain codes and
      using the rough set (RS) method to enhance the ROIs, secondly segment the mass
      region from the location ROIs with an improved vector field convolution (VFC)
      snake and following extract features from the mass region and its surroundings,
      and then establish features database with 32 dimensions; finally, these features
      are used as input to several classification techniques. In our work, the random
      forest is used and compared with support vector machine (SVM), genetic algorithm
      support vector machine (GA-SVM), particle swarm optimization support vector
      machine (PSO-SVM), and decision tree. The effectiveness of our method is
      evaluated by a comprehensive and objective evaluation system; also, Matthew's
      correlation coefficient (MCC) indicator is used. Among the state-of-the-art
      classifiers, our method achieves the best performance with best accuracy of
      97.73%, and the MCC value reaches 0.8668 and 0.8652 in unique DDSM database and
      both two databases, respectively. Experimental results prove that the proposed
      method outperforms the other methods; it could consider applying in CAD systems
      to assist the physicians for breast cancer diagnosis.

PMID- 25776768
TI  - Conversion of Radiology Reporting Templates to the MRRT Standard.
AB  - In 2013, the Integrating the Healthcare Enterprise (IHE) Radiology workgroup
      developed the Management of Radiology Report Templates (MRRT) profile, which
      defines both the format of radiology reporting templates using an extension of
      Hypertext Markup Language version 5 (HTML5), and the transportation mechanism to
      query, retrieve, and store these templates. Of 200 English-language report
      templates published by the Radiological Society of North America (RSNA),
      initially encoded as text and in an XML schema language, 168 have been converted
      successfully into MRRT using a combination of automated processes and manual
      editing; conversion of the remaining 32 templates is in progress. The automated
      conversion process applied Extensible Stylesheet Language Transformation (XSLT)
      scripts, an XML parsing engine, and a Java servlet. The templates were validated
      for proper HTML5 and MRRT syntax using web-based services. The MRRT templates
      allow radiologists to share best-practice templates across organizations and have
      been uploaded to the template library to supersede the prior XML-format
      templates. By using MRRT transactions and MRRT-format templates, radiologists
      will be able to directly import and apply templates from the RSNA Report Template
      Library in their own MRRT-compatible vendor systems. The availability of MRRT
      format reporting templates will stimulate adoption of the MRRT standard and is
      expected to advance the sharing and use of templates to improve the quality of
      radiology reports. 

PMID- 25776769
TI  - Dynamic Contrast-Enhanced MRI in the Study of Brain Tumors. Comparison Between
      the Extended Tofts-Kety Model and a Phenomenological Universalities (PUN)
      Algorithm.
AB  - Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) is a well
      established technique for studying blood-brain barrier (BBB) permeability that
      allows measurements to be made for a wide range of brain pathologies, including
      multiple sclerosis and brain tumors (BT). This latter application is particularly
      interesting, because high-grade gliomas are characterized by increased
      microvascular permeability and a loss of BBB function due to the structural
      abnormalities of the endothelial layer. In this study, we compared the extended
      Tofts-Kety (ETK) model and an extended derivate class from phenomenological
      universalities called EU1 in 30 adult patients with different BT grades. A total
      of 75 regions of interest were manually drawn on the MRI and subsequently
      analyzed using the ETK and EU1 algorithms. Significant linear correlations were
      found among the parameters obtained by these two algorithms. The means of R (2)
      obtained using ETK and EU1 models for high-grade tumors were 0.81 and 0.91, while
      those for low-grade tumors were 0.82 and 0.85, respectively; therefore, these two
      models are equivalent. In conclusion, we can confirm that the application of the
      EU1 model to the DCE-MRI experimental data might be a useful alternative to
      pharmacokinetic models in the study of BT, because the analytic results can be
      generated more quickly and easily than with the ETK model. 

PMID- 25776770
TI  - Aggressive primary cutaneous B-cell lymphomas show increased Angiopoietin-2
      induced angiogenesis.
AB  - Primary cutaneous large B-cell lymphomas, leg type (PCLBCL/LT) are primary
      cutaneous B-cell lymphoma (PCBCL) with an intermediate prognosis. Therefore,
      antracycline-based polychemotherapy combined with rituximab has been recommended
      as first-line treatment. Yet, despite this regimen, the 5-year survival rate
      remains 50-66% only. Angiogenesis, the formation of a vascular network, is
      essential for the pathogenesis of nodal lymphomas. So far, no study has analysed
      angiogenesis and its key factors in PCLBCL/LT. The present study was aimed at
      characterizing angiogenesis in PCLBCL/LT to identify the angiogenic molecules as
      potential therapeutic targets. The intra-tumoral microvessel density (MVD) was
      assessed by immunohistochemical studies of CD20 and CD31. The MVD was higher in
      PCLBCL/LT compared with indolent PCBCL. Analyses of open-source microarray data
      showed correlation between the angiogenic molecule angiopoietin-2 (Ang-2) and pan
      endothelial cell markers. ELISA studies determined a shift between Ang-2 and Ang
      1 towards Ang-2 in the peripheral blood of PCLBCL/LT patients. Immunofluorescence
      costainings against the Ang receptor Tie2/angiogenic integrins/CD34 revealed that
      the vasculature in both aggressive and indolent PCBCL tumors harbours an
      endothelial cell subpopulation with reduced expression of Tie2. In contrast, the
      alternative Ang-2 binding partners, angiogenic integrins, are strongly expressed
      in PCBCL. In line with these findings, downstream targets of Ang-2-integrin
      signalling, that is phosphorylation of focal adhesion kinase at Tyr397, and
      sprouting angiogenesis are enhanced in PCLBCL/LT. Our data present Ang-2 as a
      promising therapeutic target and anti-angiogenic therapy as a new line in
      treatment of PCLBCL/LT as a hitherto intractable disease. 

PMID- 25776792
TI  - A new Monte Carlo-based treatment plan optimization approach for intensity
      modulated radiation therapy.
AB  - Intensity-modulated radiation treatment (IMRT) plan optimization needs beamlet
      dose distributions. Pencil-beam or superposition/convolution type algorithms are
      typically used because of their high computational speed. However, inaccurate
      beamlet dose distributions may mislead the optimization process and hinder the
      resulting plan quality. To solve this problem, the Monte Carlo (MC) simulation
      method has been used to compute all beamlet doses prior to the optimization step.
      The conventional approach samples the same number of particles from each beamlet.
      Yet this is not the optimal use of MC in this problem. In fact, there are
      beamlets that have very small intensities after solving the plan optimization
      problem. For those beamlets, it may be possible to use fewer particles in dose
      calculations to increase efficiency. Based on this idea, we have developed a new
      MC-based IMRT plan optimization framework that iteratively performs MC dose
      calculation and plan optimization. At each dose calculation step, the particle
      numbers for beamlets were adjusted based on the beamlet intensities obtained
      through solving the plan optimization problem in the last iteration step. We
      modified a GPU-based MC dose engine to allow simultaneous computations of a large
      number of beamlet doses. To test the accuracy of our modified dose engine, we
      compared the dose from a broad beam and the summed beamlet doses in this beam in
      an inhomogeneous phantom. Agreement within 1% for the maximum difference and
      0.55% for the average difference was observed. We then validated the proposed MC
      based optimization schemes in one lung IMRT case. It was found that the
      conventional scheme required 10(6) particles from each beamlet to achieve an
      optimization result that was 3% difference in fluence map and 1% difference in
      dose from the ground truth. In contrast, the proposed scheme achieved the same
      level of accuracy with on average 1.2 * 10(5) particles per beamlet.
      Correspondingly, the computation time including both MC dose calculations and
      plan optimizations was reduced by a factor of 4.4, from 494 to 113 s, using only
      one GPU card. 

PMID- 25776794
TI  - [Current treatment of acute lymphoblastic leukemia in adults].
AB  - Acute lymphoblastic leukemia (ALL) is the most frequent malignant disease in
      childhood. In adults ALL comprises approximately 20 % of all forms of acute
      leukemia. In recent years substantial progress has been made with respect to the
      characterization and therapy optimization based on consecutive therapy
      optimization studies with increasingly more individualized, risk-adapted therapy
      protocols. Approximately 90 % of adult ALL patients under 55-65 years can now
      achieve complete remission. The chance of cure for adults could be increased over
      the last 30 years from less than 10 % to more than 50 %. Fundamental for the
      improvement of therapy results were an optimization of intensive chemotherapy and
      supportive treatment, integration of stem cell transplantation into the first
      line treatment, inclusion of targeted substances in the therapy concept and
      improved risk stratification in consideration of the course of the minimal
      residual disease. Due to individualized therapeutic decisions current therapy
      protocols are very complex and can only be adequately carried out in specialized
      centers. Future challenges include further optimization of therapy in older
      patients and treatment of patients refractory to chemotherapy. In Germany the
      majority of adult patients are treated according to protocols of the German
      multicenter study group for adult ALL (GMALL).

PMID- 25776793
TI  - [Chronic lymphocytic leukemia : treatment concepts in transition].
AB  - BACKGROUND: Chronic lymphocytic leukemia (CLL) is the most common leukemia in the
      Western hemisphere and mainly affects elderly patients. No curative treatment is
      currently available for this disease. TREATMENT: Advanced disease is treated
      according to the patients' fitness and comorbidity burden as well as according
      the presence of high risk genetic factors in CLL cells. The detection of del(17p)
      and/or TP53 gene mutations reflects a very unfavorable prognosis and
      refractoriness to chemotherapy (very high risk CLL). In physically fit patients
      without high comorbidity burden and without very high risk prognostic factors,
      chemoimmunotherapy containing fludarabine, cyclophosphamide, and the CD20
      antibody rituximab (FCR) is standard therapy because this regimen has been shown
      to improve overall survival. In patients with significant comorbidity burden, a
      less intense chemoimmunotherapy regimen should be administered consisting of the
      alkylating agent chlorambucil plus CD20 antibody. In very high risk patients,
      kinase inhibitors blocking the signaling transduction pathway of the B cell
      receptor have been approved since 2014. The same substances are also approved in
      relapsed CLL. However, in relapsed CLL repetitive administration of
      chemoimmunotherapy is still an alternative treatment option, especially if the
      first remission was longer lasting (> 24 months). Allogeneic hematopoietic stem
      cell transplantation in very high risk CLL or early relapsed disease has become
      less important than in the past. In some patients considering the risk of the
      transplantation versus the risk of failing to respond to the new treatment
      option, this procedure might still be the treatment of choice in order to achieve
      long-lasting remissions. CONCLUSION: In the choice of treatment for patients with
      CLL, several factors must be considered. Because of the broad spectrum of
      treatment options, therapy within a clinical study is still the best treatment
      option.

PMID- 25776795
TI  - The newly nonsporulated characterization of an Aspergillus fumigatus isolate from
      an immunocompetent patient and its clinic indication.
AB  - Aspergillus fumigatus (A. fumigatus) commonly produces abundant and heavily
      melanized infectious conidia, which are the primary agents that cause invasive
      aspergillosis (IA) in immunocompromised patients. We isolated a white
      nonsporulating A. fumigatus strain (A1j) from an immunocompetent patient. It was
      identified by histopathological examination and morphological observation, and
      subsequently confirmed by DNA sequencing of internal transcribed spacer (ITS)
      regions and partial beta-tubulin genes. Neither a long waiting time nor passage
      on various medium types could stimulate the formation of spores and pigment. No
      significant relative difference was found in sensitivity to antifungal agents or
      cell wall destabilizing reagents, as compared to wild-type A. fumigatus Af293.
      Nevertheless, A1j was hypovirulent in the immunosuppressed mice model, consistent
      with the good result in our patient. RNA deep-sequencing analysis (RNA-seq)
      revealed that hundreds of transcripts were significantly dysregulated, including
      those related to pigmentation and sporulation. qRT-PCR confirmed the anergic
      state of key regulator brlA for sporulation under the induction of conidiation
      conditions, but without mutation. To the best of our knowledge, this is the first
      report of a white, nonsporulating A. fumigatus strain infection in an
      immunocompetent patient. In our opinion, A1j may represent a mutant of typical A.
      fumigatus, providing a new clue for identification of clinical A. fumigatus
      isolates. Furthermore, the good prognosis of our patient and the reduced
      virulence in the mice model infected with A1j highlight the potential of
      sporulation inhibitors as a new generation of antifungal agents. 

PMID- 25776796
TI  - A continuous-flow mass biosensor for the real-time dynamic analysis of protease
      inhibition.
AB  - A flow injection analysis-quartz crystal microbalance (FIA-QCM) biosensor was
      developed for probing the dynamic interactions during protease inhibition. Being
      sensitive to conformation features of different proteases, this continuous-flow
      sensor has potential for structural-functional analysis and inhibitor selection. 

PMID- 25776797
TI  - Adsorption of Disperse Orange 30 dye onto activated carbon derived from Holm Oak
      (Quercus Ilex) acorns: A 3(k) factorial design and analysis.
AB  - In this study, samples of activated carbon were prepared from Holm Oak acorns by
      chemical activation with H3PO4, ZnCl2 and KOH as activating agents. The samples
      were characterized by SEM, BET, FTIR and elemental analysis, and were then
      evaluated for the removal of Disperse Orange 30 (DO30) dyes from aqueous
      solutions. A 3(k) factorial design was used to determine the interaction effects
      of carbonization temperature, pH, dosage of adsorbent and type of activating
      agent on the amount of dye removal. Also, level of effectiveness factors were
      determined by conducting regression models for maximum adsorption efficiency. Of
      all the samples, the sample generated using ZnCl2 as an activating agent showed a
      maximum dye removal efficiency of 93.5% at a carbonization temperature of 750 
      degrees C, a pH of 2 and an adsorbent dosage of 0.15 g/25 ml. The analysis shows
      that the adsorption process depends significantly on the type of activating agent
      used in the preparation of activated carbon. 

PMID- 25776798
TI  - Predictors, spatial distribution, and occurrence of woody invasive plants in
      subtropical urban ecosystems.
AB  - We examined the spatial distribution, occurrence, and socioecological predictors
      of woody invasive plants (WIP) in two subtropical, coastal urban ecosystems: San
      Juan, Puerto Rico and Miami-Dade, United States. These two cities have similar
      climates and ecosystems typical of subtropical regions but differ in
      socioeconomics, topography, and urbanization processes. Using permanent plot
      data, available forest inventory protocols and statistical analyses of geographic
      and socioeconomic spatial predictors, we found that landscape level distribution
      and occurrence of WIPs was not clustered. We also characterized WIP composition
      and occurrence using logistic models, and found they were strongly related to the
      proportional area of residential land uses. However, the magnitude and trend of
      increase depended on median household income and grass cover. In San Juan, WIP
      occurrence was higher in areas of high residential cover when incomes were low or
      grass cover was low, whereas the opposite was true in Miami-Dade. Although Miami
      Dade had greater invasive shrub cover and numbers of WIP species, San Juan had
      far greater invasive tree density, basal area and crown cover. This study
      provides an approach for incorporating field and available census data in
      geospatial distribution models of WIPs in cities throughout the globe. Findings
      indicate that identifying spatial predictors of WIPs depends on site-specific
      factors and the ecological scale of the predictor. Thus, mapping protocols and
      policies to eradicate urban WIPs should target indicators of a relevant scale
      specific to the area of interest for their improved and proactive management. 

PMID- 25776799
TI  - What you see is what you expect: rapid scene understanding benefits from prior
      experience.
AB  - Although we are able to rapidly understand novel scene images, little is known
      about the mechanisms that support this ability. Theories of optimal coding assert
      that prior visual experience can be used to ease the computational burden of
      visual processing. A consequence of this idea is that more probable visual inputs
      should be facilitated relative to more unlikely stimuli. In three experiments, we
      compared the perceptions of highly improbable real-world scenes (e.g., an
      underwater press conference) with common images matched for visual and semantic
      features. Although the two groups of images could not be distinguished by their
      low-level visual features, we found profound deficits related to the improbable
      images: Observers wrote poorer descriptions of these images (Exp. 1), had
      difficulties classifying the images as unusual (Exp. 2), and even had lower
      sensitivity to detect these images in noise than to detect their more probable
      counterparts (Exp. 3). Taken together, these results place a limit on our
      abilities for rapid scene perception and suggest that perception is facilitated
      by prior visual experience. 

PMID- 25776800
TI  - Molecular interactions between gold nanoparticles and model cell membranes.
AB  - The interactions between nanoparticles (NPs) and cells are of huge interest
      because NPs have been extensively researched for biomedical applications. For the
      cellular entry of NPs, it remains unclear how the cell membrane molecules respond
      to the exposure of NPs due to a lack of appropriate surface/interface-sensitive
      techniques to study NP-cell membrane interactions in situ in real time. In this
      study, sum frequency generation (SFG) vibrational spectroscopy was employed to
      examine the interactions between lipid bilayers (serving as model mammalian cell
      membranes) and Au NPs of four different sizes with the same mass, or the same NP
      number, or the same NP surface area. It was found that lipid flip-flop was
      induced by Au NPs of all four sizes. Interestingly, the lipid flip-flop rate was
      found to increase as the Au NP size increased with respect to the same particle
      number or the same NP surface area. However, the induced lipid flip-flop rate was
      the same for Au NPs with different sizes with the same mass, which was
      interpreted by the same "effective surface contact area" between Au NPs and the
      model cell membrane. We believe that this study provided the first direct
      observation of the lipid flip-flop induced by the interactions between Au NPs and
      the model mammalian cell membrane. 

PMID- 25776802
TI  - Acetyl-l-carnitine prevents homocysteine-induced suppression of Nrf2/Keap1
      mediated antioxidation in human lens epithelial cells.
AB  - Previous studies have revealed that high levels of serum homocysteine (Hcy) are
      closely associated with the development of juvenile and age-related cataracts. An
      increased concentration of Hcy is likely to induce gene specific demethylation in
      DNA promoter regions. The aim of the present study was to prevent this
      demethylation by administering acetyl-l-carnitine (ALCAR) to human lens
      epithelial cells (HLECs). Different concentrations of Hcy were used to treat
      HLECs for 3, 6, 12 and 24 h and the findings were used to determine the optimum
      dose to induce endoplasmic reticulum (ER) stress. Similarly, the concentration of
      ALCAR was standardized. The production of reactive oxygen species (ROS) and the
      percentage of cells undergoing cell death were measured. The levels of
      antioxidants, ER stress-associated proteins, mRNA levels of nuclear factor
      erythroid-2-related factor 2 (Nrf2), Kelch-like ECH-associated protein 1 (Keap1)
      and promoter DNA methylation of the Keap1 gene were also assessed. Hcy was
      observed to induce ER stress, produce ROS and lead to cell death. However,
      administration of ALCAR prevented these effects to a significant degree.
      Additionally, western blot analysis revealed that ALCAR increased the levels of
      antioxidant proteins, including catalase, superoxide dismutase, glutathione
      peroxidase, Nrf2, Keap1 and glutathione. Similarly, the reverse transcription
      quantitative polymerase chain reaction experiments on Nrf2 and Keap1, as well as
      the bisulfite genomic DNA sequencing analysis revealed a preventive effect of
      ALCAR against Hcy-induced ER stress. The ER stress-induced activation of the
      unfolded protein response is responsible for demethylation of Keap1 promoter DNA
      to activate the expression of the Keap1 protein, which then increases the
      targeting of Nrf2 for proteosomal degradation. This decrease in Nrf2 activity
      represses the transcription of numerous antioxidant enzyme genes and alters the
      redox-balance towards lens oxidation. However, treatment with ALCAR led to
      significant protection from these effects. The present results suggested that
      ALCAR either prevents or ameliorates the actions of the antioxidant system in
      HLECs at the level of the protein and the gene. Further advanced studies are
      required for the development of ALCAR as an anti-cataract agent.

PMID- 25776803
TI  - Ultrafast hydrogen bond dynamics and partial electron transfer after
      photoexcitation of diethyl ester of 7-(diethylamino)-coumarin-3-phosphonic acid
      and its benzoxaphosphorin analog.
AB  - The solvation dynamics after optical excitation of two phosphono-substituted
      coumarin derivatives dissolved in various solutions are studied by fluorescence
      up-conversion spectroscopy and quantum chemical simulations. The Kamlet-Taft
      analysis of the conventional absorption and emission spectra suggests weakening
      of the solvent-solute H-bonds upon optical excitation, which is in contrast to
      the results gained by the quantum simulations and earlier studies reported for
      coumarin derivatives without phosphono groups. The simulations give evidence that
      the solvent reorganisation around the excited fluorophore leads to partial
      electron transfer to the first solvation shell. The process occurs on a timescale
      between 1 and 10 ps depending on the solvent polarity and leads to a fast decay
      of the time-resolved emission signal. Using the ultrafast spectral shift of the
      time-dependent fluorescence we estimated the relaxation time of the H-bonds in
      the electronically excited state to be about 0.6 ps in water, 1.5 ps in ethanol
      and 2.8 ps in formamide. 

PMID- 25776804
TI  - On the power of the test for cluster bias.
AB  - Cluster bias refers to measurement bias with respect to the clustering variable
      in multilevel data. The absence of cluster bias implies absence of bias with
      respect to any cluster-level (level 2) variable. The variables that possibly
      cause the bias do not have to be measured to test for cluster bias. Therefore,
      the test for cluster bias serves as a global test of measurement bias with
      respect to any level 2 variable. However, the validity of the global test depends
      on the Type I and Type II error rates of the test. We compare the performance of
      the test for cluster bias with the restricted factor analysis (RFA) test, which
      can be used if the variable that leads to measurement bias is measured. It
      appeared that the RFA test has considerably more power than the test for cluster
      bias. However, the false positive rates of the test for cluster bias were
      generally around the expected values, while the RFA test showed unacceptably high
      false positive rates in some conditions. We conclude that if no significant
      cluster bias is found, still significant bias with respect to a level 2 violator
      can be detected with an RFA model. Although the test for cluster bias is less
      powerful, an advantage of the test is that the cause of the bias does not need to
      be measured, or even known. 

PMID- 25776805
TI  - Rsite: a computational method to identify the functional sites of noncoding RNAs.
AB  - There is an increasing demand for identifying the functional sites of noncoding
      RNAs (ncRNAs). Here we introduce a tertiary-structure based computational
      approach, Rsite, which first calculates the Euclidean distances between each
      nucleotide and all the other nucleotides in a RNA molecule and then determines
      the nucleotides that are the extreme points in the distance curve as the
      functional sites. By analyzing two ncRNAs, tRNA (Lys) and Diels-Alder ribozyme,
      we demonstrated the efficiency of Rsite. As a result, Rsite recognized all of the
      known functional sites of the two ncRNAs, suggesting that Rsite could be a
      potentially useful tool for discovering the functional sites of ncRNAs. The
      source codes and data sets of Rsite are available at http://www.cuilab.cn/rsite. 

PMID- 25776806
TI  - Post-traumatic stress disorder predicts future weight change in the Millennium
      Cohort Study.
AB  - OBJECTIVE: To prospectively examine the association between post-traumatic stress
      disorder (PTSD) and weight change. METHODS: Longitudinal analysis techniques were
      used to examine data (2001-2008) from Millennium Cohort Study participants,
      consisting of U.S. service members and veterans. Using the PTSD Checklist
      Civilian Version, PTSD was assessed as none, resolved, new onset, or persistent.
      Subsequent weight change was assessed as stable (<=3% loss or gain), >3% weight
      loss, >3% but <10% weight gain, and >=10% weight gain. RESULTS: Of the 38,352
      participants, 2391 (6.2%) had PTSD (838 resolved, 1024 new onset, and 529
      persistent), and 11% of participants subsequently had >=10% weight gain. In
      multivariable models, PTSD was associated with higher odds of >=10% weight gain
      (new onset OR: 1.44 [95% CI: 1.20-1.73]; persistent OR: 1.51 [CI: 1.17-1.96];
      resolved OR: 1.30 [CI: 1.05-1.60]) compared with those without PTSD. New-onset
      and persistent PTSD were also associated with higher odds of >3% weight loss (OR:
      1.41 [CI: 1.17-1.71]; OR: 1.42 [CI: 1.09-1.86], respectively). CONCLUSIONS: PTSD
      is independently associated with a higher risk of weight gain and loss, the
      former of which leads to a higher prevalence of overweight and obesity and a
      higher risk of comorbidities associated with excessive body adiposity.

PMID- 25776807
TI  - Treatment of a urethral duplication in a dog using cyanoacrylate and coil
      embolization.

PMID- 25776819
TI  - Enantioselective intramolecular hydroacylation of unactivated alkenes: an NHC
      catalyzed robust and versatile formation of cyclic chiral ketones.
AB  - A highly enantioselective intramolecular N-heterocyclic carbene (NHC)-catalyzed
      hydroacylation reaction gives access to a range of cyclic ketones from
      unactivated olefin-substituted aldehydes (up to 99 % ee). Remarkably, aliphatic
      aldehydes were also transformed efficiently in an NHC-catalyzed hydroacylation
      reaction for the first time. 

PMID- 25776809
TI  - Acceptability of home-based chlamydia and gonorrhea testing among a national
      sample of sexual minority young adults.
AB  - CONTEXT: STDs are common among older adolescents and young adults; hence, STD
      screening is a public health priority. Home-based STD testing could be a strategy
      to improve screening rates, particularly among at-risk populations, including
      sexual minority (i.e., nonheterosexual) young adults. METHODS: Data were
      collected from a national sample of 971 sexual minority young adults aged 18-26
      through an online survey in the fall of 2013. Logistic regression analyses
      identified associations between respondents' characteristics and their
      willingness to use a home-based test for chlamydia and gonorrhea. RESULTS: A
      greater proportion of men than of women were willing to use a home-based STD test
      (81% vs. 68%). Willingness was more likely among gay than among bisexual men,
      among men insured through their parents than among the uninsured and among those
      who had had two or more sexual partners in the past year than among those who had
      had fewer (adjusted odds ratios, 2.0-2.2). Among men, students were less likely
      than the employed to report willingness for home-based testing (0.4). Among
      women, willingness was more likely among those who reported at least two partners
      in the past year than among those who reported fewer (1.6). Overall, respondents'
      most common concerns about home-based STD testing regarded test accuracy, their
      ability to do the test correctly and their preference to see a doctor for
      testing. CONCLUSIONS: Home-based STD testing may be a promising strategy for
      screening sexual minority young adults; understanding correlates of willingness
      and young adults' concerns may help inform self-testing programs.

PMID- 25776820
TI  - Peripheral neuropathies: new recommendations for neuropathic pain
      pharmacotherapy.
AB  - A recent review and meta-analysis on pharmacotherapy for neuropathic pain
      provides a precise update on treatment efficacy and adverse effects. The authors
      offer revised evidence-based recommendations for first-line therapies and
      subsequent options, but we still a need to improve individual treatment
      decisions, including nonpharmacological therapies, in affected patients.

PMID- 25776821
TI  - Traumatic brain injury: Cerebral blood flow is linked to sports-related
      concussion outcomes.

PMID- 25776825
TI  - A remarkably useless new name in rheumatology.

PMID- 25776823
TI  - Pharmacological treatment of migraine during pregnancy and breastfeeding.
AB  - Migraine affects up to 25% of women of reproductive age. In the majority of these
      women, migraine improves progressively during pregnancy, but symptoms generally
      recur shortly after delivery. As suboptimally treated migraine in pregnancy could
      have negative consequences for both mother and fetus, the primary aim of
      clinicians should be to provide optimal treatment according to stage of
      pregnancy, while minimising possible risks related to drug therapy.
      Nonpharmacological approaches are always first-line treatment, and should also be
      used to complement any required drug treatment. Paracetamol is the preferred drug
      for acute treatment throughout pregnancy. If paracetamol is not sufficiently
      effective, sporadic use of sumatriptan can be considered. NSAIDs such as
      ibuprofen can also be used under certain circumstances, though their intake in
      the first and third trimesters is associated with specific risks and
      contraindications. Preventive treatment should only be considered in the most
      severe cases. In women contemplating pregnancy, counselling is essential to
      promote a safe and healthy pregnancy and postpartum period for the mother and
      child, and should involve a dialogue addressing maternal concerns and
      expectations about drug treatment. This Review summarizes current evidence of the
      safety of the most common antimigraine medications during pregnancy and
      breastfeeding, and provides treatment recommendations for use in clinical
      practice.

PMID- 25776824
TI  - The promise of futility trials in neurological diseases.
AB  - Double-blinded randomized controlled trials (RCTs) have contributed much
      important evidence to guide treatment decisions in neurology. RCTs are relatively
      straightforward to conduct, provided that they investigate common diseases, have
      clearly defined outcome measures, and are of short duration. In neurology,
      however, many diseases are uncommon, have no consensus outcome measures, and
      develop over decades. Basic research into neurological diseases continues to
      identify candidate therapies faster than they can be tested for their clinical
      utility, leading to a 'translational gap'. Futility trials were initially
      developed in oncology to efficiently test candidate therapies in phase II trials.
      As single-arm unblinded studies, futility trials are relatively easy to conduct,
      and they generally require smaller sample sizes than RCTs. In this article, we
      discuss futility models, highlighting their advantages as well as challenges to
      their application in several neurological diseases, including Parkinson disease,
      stroke and multiple sclerosis. 

PMID- 25776826
TI  - Using axillary temperature to approximate rectal temperature in newborns.
AB  - AIM: Various factors have been shown to potentially affect the difference between
      axillary and rectal temperature measurements in newborns. We aimed to explore
      their roles and, if possible, to construct a formula that explained the
      difference. METHODS: The study was based on a consecutive sample of 175 infants,
      with a gestational age of 24-42 weeks, whose rectal and axillary temperatures
      were measured simultaneously at the neonatal unit at Skaraborg Hospital in
      Sweden. Data were analysed using multiple regressions. RESULTS: Premature infants
      had a significantly smaller mean difference (0.33 degrees C) between rectal and
      axillary temperatures than full-term infants (0.43 degrees C). Significant
      associated factors for premature infants were chronological age (p = 0.025), time
      of day (p = 0.004) and axillary temperature (p < 0.001). For full-term infants,
      the only significant associated factor was axillary temperature (p = 0.015).
      CONCLUSION: Although it is possible to construct a formula that estimates neonate
      rectal temperature based on axillary temperature with a slightly higher
      reliability than simply adding a fixed value like 0.4 degrees C, such a formula
      would be too complex to apply in practice. Adding 0.3 degrees C or 0.4 degrees C
      to the measured axillary temperature for premature infants or full-term infants,
      respectively, yields acceptable approximations in most cases.

PMID- 25776822
TI  - Expert consensus document: Mind the gaps-advancing research into short-term and
      long-term neuropsychological outcomes of youth sports-related concussions.
AB  - Sports-related concussions and repetitive subconcussive exposure are increasingly
      recognized as potential dangers to paediatric populations, but much remains
      unknown about the short-term and long-term consequences of these events,
      including potential cognitive impairment and risk of later-life dementia. This
      Expert Consensus Document is the result of a 1-day meeting convened by Safe Kids
      Worldwide, the Alzheimer's Drug Discovery Foundation, and the Andrews Institute
      for Orthopaedics and Sports Medicine. The goal is to highlight knowledge gaps and
      areas of critically needed research in the areas of concussion science, dementia,
      genetics, diagnostic and prognostic biomarkers, neuroimaging, sports injury
      surveillance, and information sharing. For each of these areas, we propose clear
      and achievable paths to improve the understanding, treatment and prevention of
      youth sports-related concussions.

PMID- 25776828
TI  - A model Ni-Al-Mo superalloy studied by ultraviolet pulsed-laser-assisted local
      electrode atom-probe tomography.
AB  - This study investigates the effects of the charge-state ratio of evaporated ions
      on the accuracy of local-electrode atom-probe (LEAP) tomographic compositional
      and structural analyses, which employs a picosecond ultraviolet pulsed laser.
      Experimental results demonstrate that the charge-state ratio is a better
      indicator of the best atom-probe tomography (APT) experimental conditions
      compared with laser pulse energy. The thermal tails in the mass spectra decrease
      significantly, and the mass resolving power (m/Deltam) increases by 87.5 and
      185.7% at full-width half-maximum and full-width tenth-maximum, respectively, as
      the laser pulse energy is increased from 5 to 30 pJ/pulse. The measured
      composition of this alloy depends on the charge-state ratio of the evaporated
      ions, and the most accurate composition is obtained when Ni2+/Ni+ is in the range
      of 0.3-20. The gamma(f.c.c.)/gamma'(L12) interface is quantitatively more diffuse
      when determined from the measured concentration profiles for higher laser pulse
      energies. Conclusions of the APT compositional and structural analyses utilizing
      the same suitable charge-state ratio are more comparable than those collected
      with the same laser pulse energy. 

PMID- 25776827
TI  - PET neuroimaging studies of [(18)F]CABS13 in a double transgenic mouse model of
      Alzheimer's disease and nonhuman primates.
AB  - Fluorine-18 labeled 2-fluoro-8-hydroxyquinoline ([(18)F]CABS13) is a promising
      positron emission tomography (PET) radiopharmaceutical based on a metal chelator
      developed to probe the "metal hypothesis of Alzheimer's disease". Herein, a
      practical radiosynthesis of [(18)F]CABS13 was achieved by radiofluorination
      followed by deprotection of an O-benzyloxymethyl group. Automated production and
      formulation of [(18)F]CABS13 resulted in 19 +/- 5% uncorrected radiochemical
      yield, relative to starting [(18)F]fluoride, with >=95% chemical and
      radiochemical purities, and high specific activity (>2.5 Ci/MUmol) within 80 min.
      Temporal PET neuroimaging studies were carried out in female transgenic B6C3
      Tg(APPswe,PSEN 1dE9)85Dbo/J (APP/PS1) and age-matched wild-type (WT) B6C3F1/J
      control mice at 3, 7, and 10 months of age. [(18)F]CABS13 showed an overall
      higher uptake and retention of radioactivity in the central nervous system of
      APP/PS1 mice versus WT mice with increasing age. However, PET/magnetic resonance
      imaging in normal nonhuman primates revealed that the tracer had low uptake in
      the brain and rapid formation of a hydrophilic radiometabolite. Identification of
      more metabolically stable (18)F-hydroxyquinolines that can be readily accessed by
      the radiochemical strategy presented herein is underway.

PMID- 25776836
TI  - A potential peptide pathway from viruses to oral lichen planus.
AB  - Oral lichen planus is an idiopathic inflammatory disease of oral mucous
      membranes, characterized by an autoimmune epidermis attack by T cells. It remains
      unknown, however, how such aggressive T cells are activated in vivo to cause
      epidermal damage. This study analyzes the relationship at the peptide level
      between viruses and oral lichen planus disease. Four potentially immunogenic
      peptides (SSSSSSS, QEQLEKA, LLLLLLA, and MLSGNAG) are found to be shared between
      HCV, EBV, HHV-7, HSV-1, and CMV and three human proteins (namely pinin,
      desmoglein-3, and plectin). The described peptide sharing might be of help in
      deciphering the still unexplained immunopathogenic pathway that leads to oral
      lichen planus.

PMID- 25776829
TI  - The cranberry flavonoids PAC DP-9 and quercetin aglycone induce cytotoxicity and
      cell cycle arrest and increase cisplatin sensitivity in ovarian cancer cells.
AB  - Cranberry flavonoids (flavonols and flavan-3-ols), in addition to their
      antioxidant properties, have been shown to possess potential in vitro activity
      against several cancers. However, the difficulty of isolating cranberry compounds
      has largely limited anticancer research to crude fractions without well-defined
      compound composition. In this study, individual cranberry flavonoids were
      isolated to the highest purity achieved so far using gravity and high performance
      column chromatography and LC-MS characterization. MTS assay indicated
      differential cell viability reduction of SKOV-3 and OVCAR-8 ovarian cancer cells
      treated with individual cranberry flavonoids. Treatment with quercetin aglycone
      and PAC DP-9, which exhibited the strongest activity, induced apoptosis, led to
      caspase-3 activation and PARP deactivation, and increased sensitivity to
      cisplatin. Furthermore, immunofluorescence microscopy and western blot study
      revealed reduced expression and activation of epidermal growth factor receptor
      (EGFR) in PAC DP-9 treated SKOV-3 cells. In addition, quercetin aglycone and PAC
      DP-9 deactivated MAPK-ERK pathway, induced downregulation of cyclin D1, DNA-PK,
      phospho-histone H3 and upregulation of p21, and arrested cell cycle progression.
      Overall, this study demonstrates promising in vitro cytotoxic and anti
      proliferative properties of two newly characterized cranberry flavonoids,
      quercetin aglycone and PAC DP-9, against ovarian cancer cells.

PMID- 25776837
TI  - Dose-intensified CHOP with rituximab (R-Double-CHOP) followed by consolidation
      high-dose chemotherapies for patients with advanced diffuse large B-cell
      lymphoma.
AB  - Even after the advent of rituximab, clinical outcomes of conventional immuno
      chemotherapy for high-risk diffuse large B-cell lymphoma (DLBCL) remain
      unsatisfactory. We retrospectively evaluated the efficacy and safety of R-Double
      CHOP (R-D-CHOP), consisting of rituximab (375 mg/m(2), day -2), cyclophosphamide
      (750 mg/m(2), day 1, 2), doxorubicin (50 mg/m(2), day 1, 2), vincristine [1.4
      mg/m(2) (maximum 2.0 mg/body), day 1], and prednisolone (50 mg/m(2), day 1-5),
      followed by consolidation high-dose chemotherapy. This treatment was given to 51
      de novo DLBCL patients with a median age of 54 (range 19-65), who were
      categorized as high/high-intermediate risk by the age-adjusted International
      Prognostic Index. Treatment was given every 3 weeks up to three courses. The
      overall response and the complete response rate for R-D-CHOP were 94 and 78 %,
      respectively. A total of 30 responders proceeded to high-dose chemotherapy
      followed by autologous stem cell transplantation (HDC/ASCT), whereas 16 received
      high-dose methotrexate (HD-MTX) alternatively. The 3-year overall survival and
      the event-free survival for all patients were 78 and 61 %, respectively. Major
      adverse events included hematological toxicities, but there were no treatment
      related deaths during the observation period. We conclude that the R-D-CHOP
      regimen followed by HDC/ASCT or HD-MTX is a promising treatment option for
      younger patients with highly advanced DLBCL.

PMID- 25776838
TI  - Bear bile powder inhibits angiogenesis in vivo and in vitro.
AB  - OBJECTIVE: To evaluate the effect of bear bile powder (BBP) on angiogenesis, and
      investigate the underlying molecular mechanisms. METHODS: A chick embryo
      chorioallantoic membrane (CAM) assay was used to evaluate the angiogensis in
      vivo. Human umbilical vein endothelial cells (HUVECs) were treated with 0, 0.25,
      0.5, 0.75, and 1.0 mg/mL of BBP for 24, 48 and 72 h, respectively. The 3-(4, 5
      dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay was performed to
      determine the viability of HUVECs. Cell cycle progression of HUVECs was examined
      by fluorescence-activated cell sorting (FACS) analysis with propidium iodide
      staining. HUVEC migration was determined by wound healing method. An ECMatrix gel
      system was used to evaluate the tube formation of HUVECs. The mRNA and protein
      expression of vascular endothelial growth factor (VEGF)-A in both HUVECs and
      HepG2 human cells were examined by reverse transcription-polymerase chain
      reaction and enzyme linked immunosorbent assay, respectively. RESULTS: Compared
      with the untreated group, BBP inhibited angiogenesis in vivo in the CAM model (P<
      0.01). In addition, treatment with 0.25-1 mg/mL of BBP for 24, 48, or 72 h
      respectively reduced cell viability by 14%-27%, 29%-69% and 33%-91%, compared
      with the untreated control cells (P< 0.01). Additionally, BBP inhibited the
      proliferation of HUVECs via blocking the cell cycle G to S progression, compared
      with the S phase of untreated cells 48.05%+/- 5.00%, 0.25-0.75 mg/mL BBP reduced
      S phase to 40.38%+/- 5.30%, 36.54+/- 4.50% and 32.13+/- 3.50%, respectively
      (Pglt; 0.05). Moreover, BBP inhibited the migration and tube formation of HUVECs,
      compared with the tube length of untreated cells 100%+/- 12%, 0.25-0.75 mg/mL BBP
      reduced the tube length to 62%+/- 9%, 43%+/- 5% and 17%+/- 3%, respectively (p<
      0.01). Furthermore, BBP treatment down-regulated the mRNA and protein expression
      levels of VEGF-A in both HepG2 cells and HUVECs. CONCLUSION: BBP could inhibit
      the angiogenesis by reducing VEGF-A expression, which may, in part, explain its
      anti-tumor activity.

PMID- 25776839
TI  - An investigation of the effects of curcumin on anxiety and depression in obese
      individuals: A randomized controlled trial.
AB  - OBJECTIVE: To investigate the effectiveness of curcumin, a natural polyphenolic
      compound with antioxidant and anti-inflammatory activities, on the frequency of
      symptoms of anxiety and depression in obese individuals. METHODS: In this double
      blind, cross-over trial, 30 obese subjects were randomized to receive either
      curcumin (1 g/day) or placebo for a period of 30 days. Following a wash-out
      interval of 2 weeks, each subject was crossed over to the alternative regimen for
      a further 30 days. Severity of anxiety and depression was assessed at baseline
      and at weeks 4, 6 and 10 of the trial using the Beck Anxiety Inventory (BAI) and
      Beck Depression Inventory (BDI) scales, respectively. RESULTS: Mean BAI score was
      found to be significantly reduced following curcumin therapy (P=0.03). However,
      curcumin supplementation did not exert any significant impact on BDI scores
      (P=0.7). CONCLUSION: Curcumin has a potential anti-anxiety effect in individuals
      with obesity.

PMID- 25776840
TI  - Qingre quyu granule stabilizes plaques through inhibiting the expression of
      tenascin-C in patients with severe carotid stenosis.
AB  - OBJECTIVE: To investigate the therapeutic effects of Qingre Quyu Granule (QQG) on
      the patients with severe carotid stenosis, and to explore the mechanism of it.
      METHODS: Ninety-six patients with severe carotid stenosis were enrolled in the
      study and were classified into a QQG group (n=48) and a control group (n=48)
      randomly using consecutively numbered envelopes. The patients in the QQG group
      were given QQG and Western medicine, those in the control group were given
      Western medicine merely, the course of treatment was 16 weeks. All patients went
      through endarterectomy after treatment. Plaques were subjected to the analysis of
      CD3, CD68, soluble intercellular adhesion molecule 1 (ICAM-1), matrix
      metalloprotease-9 (MMP-9), CD40L, tenascin-C, and collagen content lipid content
      by immunohistochemistry or polarized light analysis. RESULTS: By the end of
      experiment, the expressions of CD3, CD68, ICAM-1, MMP9, CD40L and tenascin-C on
      the plaques were statistically significant lower in the QQG group compared with
      the control group(P<0.01). The lipid content of the plaque was also significantly
      lower in the QQG group compared with the control group (P<0.01). The interstitial
      collagen in the tissue sections of the plaques was also significantly higher in
      the QQG group in comparison with the control group (P<0.01). CONCLUSION: QQG
      could stabilize carotid artery plaques through inhibiting pro-inflammation
      factors and restraining the tenascin-C and MMP9 pathway.

PMID- 25776841
TI  - L-tetrahydropalamatine inhibits tumor necrosis factor-alpha-induced monocyte
      endothelial cell adhesion through downregulation of intercellular adhesion
      molecule-1 and vascular cell adhesion molecule-1 involving suppression of nuclear
      factor-kappa B signaling pathway.
AB  - OBJECTIVE: To investigate whether I-tetrahydropalmatine (I-THP), an alkaloid
      mainly present in Corydalis family, could ameliorate early vascular inflammatory
      responses in atherosclerotic processes. METHODS: Fluorescently labeled monocytes
      were co-incubated with human umbilical vein endothelial cells (HUVECs), which
      were pretreated with I-THP and then simulated with tumor necrosis factor (TNF)
      alpha in absence of I-THP to determine if I-THP could reduce thecytokine-induced
      adhesion of monocytes to HUVECs. Then I-THP were further studied the underlying
      mechanisms through observing the transcriptional and translational level of
      intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1
      (VCAM-1) and the nuclear translocation of nuclear factor (NF)-kappa B in HUVECs.
      RESULTS: L-THP could block TNF-alpha-induced adhesion of monocytes to HUVECs and
      could significantly inhibited the expression of ICAM-1 and VCAM-1 on cell surface
      by 31% and 36% at 30 MU mol/L. L-THP pretreatment could also markedly reduce
      transcriptional and translational level of VCAM-1 as well as mildly reduce the
      total protein and mRNA expression levels of ICAM-1. Furthermore, I-THP attenuated
      TNF-alpha-stimulated NF-kappa B nuclear translocation. CONCLUSION: These results
      provide evidences supporting that I-THP could be a promising compound in the
      prevention and treatment of the early vascular inflammatory reaction in
      atherosclerosis by inhibiting monocyte adhesion to vascular endothelial cell
      through downregulating ICAM-1 and VCAM-1 in vascular endothelial cell based on
      suppressing NF-kappa B.

PMID- 25776842
TI  - Chemokine-mediated immune responses in the female genital tract mucosa.
AB  - The genital tract mucosa is the site where sexually transmitted infections gain
      entry to the host. The immune response at this site is thus critical to provide
      innate protection against pathogens that are seen for the very first time as well
      as provide long-term pathogen-specific immunity, which would be required for an
      effective vaccine against sexually transmitted infection. A finely regulated
      immune response is therefore required to provide an effective barrier against
      pathogens without compromising the capacity of the genital tract to allow for
      successful conception and fetal development. We review recent developments in our
      understanding of the immune response in the female genital tract to infectious
      pathogens, using herpes simplex virus-2, human immunodeficiency virus-1 and
      Chlamydia trachomatis as examples, with a particular focus on the role of
      chemokines in orchestrating immune cell migration necessary to achieve effective
      innate and adaptive immune responses in the female genital tract. 

PMID- 25776844
TI  - Heterozygosity for the common perforin mutation, p.A91V, impairs the cytotoxicity
      of primary natural killer cells from healthy individuals.
AB  - The production and delivery of functional perforin (PRF; PRF1 gene) by cytotoxic
      lymphocytes maintains immune homeostasis and tumour immune surveillance. In
      humans, inheritance of the common PRF1 polymorphism, p.A91V, (c.272C>T) found in
      8-9% of the Caucasian population, with another mutated allele resulting in
      reduced PRF function or trafficking, has been shown to result in
      hyperinflammatory diseases and/or haematological cancers. In this study, we
      sought to investigate the function of p.A91V on a wild-type (WT) perforin
      background. We first developed an assay that distinguishes the relative levels of
      transcription of individual PRF1 alleles, including p.A91V. The p.A91V allele was
      seen to be expressed at similar levels as the WT allele in primary human natural
      killer (NK) cells, ruling out that allelic expression imbalance influenced their
      function. We then demonstrated that the p.A91V mutation results in protein
      misfolding and an appreciable reduction in NK-cell cytotoxicity in healthy
      carriers of p.A91V. We propose that this level of cytotoxic dysfunction may
      readily account for the predisposition to immune-mediated disease in individuals
      homozygous for p.A91V. Also, the fact that monoallelic mutations of PRF1 decrease
      NK-cell cytotoxicity should be considered in individuals presenting with the
      manifestations of immune deficiency states that impinge on NK-cell cytotoxicity. 

PMID- 25776843
TI  - Shigella IpaB and IpaD displayed on L. lactis bacterium-like particles induce
      protective immunity in adult and infant mice.
AB  - Shigella spp. are among the enteric pathogens with the highest attributable
      incidence of moderate-to-severe diarrhea in children under 5 years of age living
      in endemic areas. There are no vaccines available to prevent this disease. In
      this work, we investigated a new Shigella vaccine concept consisting of
      nonliving, self-adjuvanted, Lactococcus lactis bacterium-like particles (BLP)
      displaying Shigella invasion plasmid antigen (Ipa) B and IpaD and examined its
      immunogenicity and protective efficacy in adult and newborn/infant mice immunized
      via the nasal route. Unique advantages of this approach include the potential for
      broad protection due to the highly conserved structure of the Ipas and the safety
      and practicality of a probiotic-based mucosal/adjuvant delivery platform.
      Immunization of adult mice with BLP-IpaB and BLP-IpaD (BLP-IpaB/D) induced high
      levels of Ipa-specific serum IgG and stool IgA in a dose-dependent manner. Immune
      responses and protection were enhanced by BLP delivery. Vaccine-induced serum
      antibodies exhibited opsonophagocytic and cytotoxic neutralizing activity, and
      IpaB/D IgG titers correlated with increased survival post-challenge. Ipa-specific
      antibody secreting cells were detected in nasal tissue and lungs, as well as IgG
      in bronchoalveolar lavage. Bone marrow cells produced IpaB/D-specific antibodies
      and contributed to protection after adoptive transfer. The BLP-IpaB/D vaccine
      conferred 90% and 80% protection against S. flexneri and S. sonnei, respectively.
      Mice immunized with BLP-IpaB/D as newborns also developed IpaB and IpaD serum
      antibodies; 90% were protected against S. flexneri and 44% against S. sonnei. The
      BLP-IpaB/D vaccine is a promising candidate for safe, practical and potentially
      effective immunization of children against shigellosis. 

PMID- 25776845
TI  - Delayed control of herpes simplex virus infection and impaired CD4(+) T-cell
      migration to the skin in mouse models of DOCK8 deficiency.
AB  - DOCK8 deficiency in humans and mice leads to multiple defects in immune cell
      numbers and function. Patients with this immunodeficiency have a high morbidity
      and mortality, and are distinguished by chronic cutaneous viral infections,
      including those caused by herpes simplex virus (HSV). The underlying mechanism of
      the specific susceptibility to these chronic cutaneous viral infections is
      currently unknown, largely because the effect of DOCK8 deficiency has not been
      studied in suitable models. A better understanding of these mechanisms is
      required to underpin the development of more specific therapies. Here we show
      that DOCK8-deficient mice have poor control of primary cutaneous herpes simplex
      lesions and this is associated with increased virus loads. Furthermore, DOCK8
      deficient mice showed a lack of CD4(+) T-cell infiltration into HSV-infected
      skin. 

PMID- 25776846
TI  - Human thymic epithelial primary cells produce exosomes carrying tissue-restricted
      antigens.
AB  - Exosomes are nano-sized vesicles released by cells into the extracellular space
      and have been shown to be present in thymic tissue both in mice and in humans.
      The source of thymic exosomes is however still an enigma and hence it is not
      known whether thymic epithelial cells (TECs) are able to produce exosomes. In
      this work, we have cultured human TECs and isolated exosomes. These exosomes
      carry tissue-restricted antigens (TRAs), for example, myelin basic protein and
      desmoglein 3. The presence of TRAs indicates a possible role for thymic
      epithelium-derived exosomes in the selection process of thymocytes. The key
      contribution of these exosomes could be to disseminate self-antigens from the
      thymic epithelia, thus making them more accessible to the pool of maturing
      thymocytes. This would increase the coverage of TRAs within the thymus, and
      facilitate the process of positive and negative selection. 

PMID- 25776847
TI  - The role of chemokines in cutaneous immunosurveillance.
AB  - The skin serves as a critical barrier against pathogen entry. This protection is
      afforded by an array of skin-resident immune cells, which act as first-line
      responders against barrier breach and infection. The recruitment and positioning
      of these cells is controlled at multiple levels by endothelial cells, pericytes,
      perivascular macrophages and mast cells, and by the fibroblasts in the dermis and
      keratinocytes in the epidermis. Chemokine signalling through chemokine receptors
      expressed by the various leukocyte subsets is critical for their trafficking into
      and within the skin. The role of chemokines in the skin is complex, and remains
      incompletely understood despite three decades of investigation. Here, we review
      the roles that different chemokine pathways play in the skin, and highlight the
      recent developments in the field. 

PMID- 25776848
TI  - Comparing methods of measuring geographic patterns in temporal trends: an
      application to county-level heart disease mortality in the United States, 1973 to
      2010.
AB  - PURPOSE: To demonstrate the implications of choosing analytical methods for
      quantifying spatiotemporal trends, we compare the assumptions, implementation,
      and outcomes of popular methods using county-level heart disease mortality in the
      United States between 1973 and 2010. METHODS: We applied four regression-based
      approaches (joinpoint regression, both aspatial and spatial generalized linear
      mixed models, and Bayesian space-time model) and compared resulting inferences
      for geographic patterns of local estimates of annual percent change and
      associated uncertainty. RESULTS: The average local percent change in heart
      disease mortality from each method was -4.5%, with the Bayesian model having the
      smallest range of values. The associated uncertainty in percent change differed
      markedly across the methods, with the Bayesian space-time model producing the
      narrowest range of variance (0.0-0.8). The geographic pattern of percent change
      was consistent across methods with smaller declines in the South Central United
      States and larger declines in the Northeast and Midwest. However, the geographic
      patterns of uncertainty differed markedly between methods. CONCLUSIONS: The
      similarity of results, including geographic patterns, for magnitude of percent
      change across these methods validates the underlying spatial pattern of declines
      in heart disease mortality. However, marked differences in degree of uncertainty
      indicate that Bayesian modeling offers substantially more precise estimates.

PMID- 25776850
TI  - Images in vascular medicine. Dysphagia aortica with left atrial compression.

PMID- 25776849
TI  - Characterization of macrophage--cancer cell crosstalk in estrogen receptor
      positive and triple-negative breast cancer.
AB  - Tumor heterogeneity may broadly influence the activation of tumor-associated
      macrophages. We aimed to dissect how breast cancer cells of different molecular
      characteristics contribute to macrophage phenotype and function. Therefore, we
      performed whole transcriptome sequencing of human monocytes that were co-cultured
      with estrogen receptor positive (ER(+)) or triple-negative (TNBC) breast cancer
      cell lines and studied the biological responses related to the differential gene
      activation in both monocytes and cancer cells by pathway analysis. ER(+) and TNBC
      cancer cell lines induced distinctly different macrophage phenotypes with
      different biological functions, cytokine and chemokine secretion, and morphology.
      Conversely, ER(+) and TNBC breast cancer cell lines were distinctly influenced by
      the presence of macrophages. ER(+) cells demonstrated up-regulation of an acute
      phase inflammatory response, IL-17 signaling and antigen presentation pathway,
      whereas thioredoxin and vitamin D3 receptor pathways were down-regulated in the
      respective macrophages. The TNBC educated macrophages down-regulated citrulline
      metabolism and differentiated into M2-like macrophages with increased MMR protein
      expression and CCL2 secretion. These data demonstrate how different cancer cells
      educate the host cells to support tumor growth and might explain why high
      infiltration of macrophages in TNBC tumors associates with poor prognosis. 

PMID- 25776851
TI  - Images in vascular medicine. 'Ski-jump' toenails--a phenotypic manifestation of
      primary lymphedema.

PMID- 25776853
TI  - Comparative study on the antioxidant activities of extracts of Coreopsis
      tinctoria flowering tops from Kunlun Mountains, Xinjiang, north-western China.
AB  - Coreopsis tinctoria flowering tops (CTFs) from the Kunlun Mountains in Xinjing
      (north-western China) have been used for tea production for about a century. This
      study aims to assess the antioxidant activities and total phenolic, flavonoid and
      proanthocyanidin contents of various solvent extracts of CTF. CTF was extracted
      using n-hexane, chloroform, ethyl acetate, n-butanol, 75% aqueous ethanol (AEE)
      and water. The antioxidant activities of the CTF extracts were investigated
      through DPPH, ABTS, *OH, *O2(-), total antioxidant capacity and reducing power
      assays. The results showed that n-butanol extract showed the highest contents of
      total phenols and flavonoids, with DPPH, ABTS and *OH radical-scavenging
      activities with IC50 values of 134, 90.72 and 13.8 MUg mL(-1), respectively. The
      AEE demonstrated the strongest DPPH and ABTS radical-scavenging activities, with
      IC50 values of 103 and 75.16 MUg mL(-1), respectively. Given its high antioxidant
      effect, CTF is a good source of natural antioxidants or functional food
      materials.

PMID- 25776852
TI  - Turning Bone Morphogenetic Protein 2 (BMP2) on and off in Mesenchymal Cells.
AB  - The concentration, location, and timing of bone morphogenetic protein 2 (BMP2,
      HGNC:1069, GeneID: 650) gene expression must be precisely regulated. Abnormal
      BMP2 levels cause congenital anomalies and diseases involving the mesenchymal
      cells that differentiate into muscle, fat, cartilage, and bone. The molecules and
      conditions that influence BMP2 synthesis are diverse. Understandably, complex
      mechanisms control Bmp2 gene expression. This review includes a compilation of
      agents and conditions that can induce Bmp2. The currently known trans-regulatory
      factors and cis-regulatory elements that modulate Bmp2 expression are summarized
      and discussed. Bone morphogenetic protein 2 (BMP2, HGNC:1069, GeneID: 650) is a
      classical morphogen; a molecule that acts at a distance and whose concentration
      influences cell behavior. In mesenchymal cells, the concentration of BMP2
      influences myogenesis, adipogenesis, chondrogenesis, and osteogenesis. Because
      the amount, timing, and location of BMP2 synthesis influence the allocation of
      cells to muscle, fat, cartilage, and bone, the mechanisms that regulate the Bmp2
      gene are crucial. Key early mesodermal events that require precise Bmp2
      regulation include heart specification and morphogenesis. Originally named for
      its osteoinductive properties, healing fractures requires BMP2. The human Bmp2
      gene also has been linked to osteoporosis and osteoarthritis. In addition, all
      forms of pathological calcification in the vasculature and in cardiac valves
      involve the pro-osteogenic BMP2. The diverse tissues, mechanisms, and diseases
      influenced by BMP2 are too numerous to list here (see OMIM: 112261). However, in
      all BMP2-influenced pathologies, changes in the behavior and differentiation of
      pluripotent mesenchymal cells are a recurring theme. Consequently, much effort
      has been devoted to identifying the molecules and conditions that influence BMP2
      synthesis and the complex mechanisms that control Bmp2 gene expression. This
      review begins with an overview of the Bmp2 gene's chromosomal neighborhood and
      then summarizes and evaluates known regulatory mechanisms and inducers.

PMID- 25776854
TI  - Ubqln3, a testis-specific gene, is dispensable for embryonic development and
      spermatogenesis in mice.

PMID- 25776855
TI  - Meta-analysis of the predictive value of C-reactive protein for infectious
      complications in abdominal surgery.
AB  - BACKGROUND: The aim of this analysis was to assess the predictive value of C
      reactive protein (CRP) for the early detection of postoperative infectious
      complications after a variety of abdominal operations. METHODS: A meta-analysis
      of seven cohort studies from a single institution was performed. Laparoscopic
      gastric bypass and colectomies, as well as open resections of cancer of the
      colon, rectum, pancreas, stomach and oesophagus, were included. The predictive
      value of CRP was assessed by the area under the curve (AUC) of the receiver
      operating characteristic (ROC) curve. RESULTS: Of 1986 patients, 577 (29.1 (95
      per cent c.i. 27.1 to 31.3) per cent) had at least one postoperative infectious
      complication. Patients undergoing laparoscopic gastric bypass (383 patients) or
      colectomy (285), and those having open gastric (97) or colorectal (934)
      resections were combined in a meta-analysis. Patients who had resection for
      cancer of the oesophagus (41) or pancreas (246) were analysed separately owing to
      heterogeneity. CRP levels 4 days after surgery had the highest diagnostic
      accuracy (AUC 0.76, 95 per cent c.i. 0.73 to 0.78). Sensitivity and specificity
      were 68.5 (60.6 to 75.5) and 71.6 (66.6 to 76.0) per cent respectively. Positive
      and negative predictive values were 50.4 (46.0 to 54.8) and 84.3 (80.8 to 87.3)
      per cent. The threshold CRP varied according to the procedure performed.
      CONCLUSION: The negative predictive value of serum CRP concentration on day 4
      after surgery facilitates reliable exclusion of postoperative infectious
      complications.

PMID- 25776856
TI  - A nomogram for predicting the benefit of adjuvant cytokine-induced killer cell
      immunotherapy in patients with hepatocellular carcinoma.
AB  - The benefits of adjuvant cytokine-induced killer (CIK) cell immunotherapy for
      hepatocellular carcinoma (HCC) remain mixed among patients. Here, we constructed
      a prognostic nomogram to enable individualized predictions of survival benefit of
      adjuvant CIK cell treatment for HCC patients. Survival analysis showed that the
      median overall survival (OS) and progression-free survival (PFS) for patients in
      the hepatectomy/CIK combination group were 41 and 16 months, respectively,
      compared to 28 and 12 months for patients in the hepatectomy alone group
      (control). Based on multivariate analysis of the entire cohort, independent
      factors for OS were tumor size, tumor capsule, pathological grades, total
      bilirubin, albumin, prothrombin time, alpha-fetoprotein, and tumor number, which
      were incorporated into the nomogram. The survival prediction model performed
      well, as assessed by the c-index and calibration curve. Internal validation
      revealed a c-index of 0.698, which was significantly greater than the c-index
      value of the TNM (tumor-node-metastasis) staging systems of 0.634. The
      calibration curves fitted well. In conclusions, our developed nomogram resulted
      in more accurate individualized predictions of the survival benefit from adjuvant
      CIK cell treatment after hepatectomy. The model may provide valuable information
      to aid in the decision making regarding the application of adjuvant CIK cell
      immunotherapy. 

PMID- 25776857
TI  - Oxidized/reduced graphene nanoribbons facilitate charge transfer to the Fe(CN)63
      /Fe(CN)64- redox couple and towards oxygen reduction.
AB  - This study investigated the synthesis of graphene oxide nanoribbons (GONRs) and
      graphene nanoribbons (GNRs) from multiwalled carbon nanotubes (MWCNTs), and the
      behavior of thin films of MWCNTs, GONRs, and GNRs on a glassy carbon surface in
      the presence of two redox probes (Fe(CN)6(3-)/Fe(CN)6(4-) and O2) employing
      cyclic voltammetry, electrochemical impedance spectroscopy, and hydrodynamic
      voltammetry (HV) as a simple procedure for characterizing these films. The
      feasibility of using these electrochemical techniques for this purpose opens up
      the possibility of applying them to biosensors and electrocatalysts using surface
      supported MWCNT, GONR, and GNR materials. GNR1 resembles an internodal segment of
      bamboo cut lengthwise, with a shallow troughing at its center, while GNR2
      resembles stacked ribbons, each ~16 nm wide, with points of structural damage and
      points of four-ribbon connection measuring 60 nm or wider, sufficiently catalytic
      for the oxygen reduction reaction to occur, unlike the other modified electrodes
      investigated in acidic, 0.1 M KH2PO4 (pH 7.0), and 0.1 M KOH solutions (HV
      results). Transmission electron microscopy and thermogravimetric analysis were
      employed to characterize the MWCNTs, GONRs, and GNRs. 

PMID- 25776858
TI  - Training models for meniscal repairs and small joint arthroscopy.
AB  - BACKGROUND: The reduced availability of human cadavers and their associated high
      costs, coupled with an increasing requirement for meeting continuing professional
      development targets, has accentuated the need for alternative training models
      that meet current ethical standards. The aim of this study is to identify
      suitable substitutes that are accessible and cost effective for use as training
      models for meniscal repairs and small joint arthroscopy. METHOD: Ovine, bovine
      and porcine stifles were analysed for comparable anatomy to the human knee,
      arthroscopic access, arthroscopic view and ease of meniscal repair. RESULTS: The
      bovine stifle joint was found to be too large and offered limited access due to a
      large anterior fat pad and thick surrounding soft tissue. The ovine and bovine
      stifles were both easily available and had comparable anatomy to the human knee.
      Advantages of the porcine stifle include better availability and easier
      accessibility, comparable anatomy to the human knee and its relatively larger
      size that made it easier to arthroscope. CONCLUSION: Porcine stifles are cost
      effective, accessible, allow for meniscal repair and are suitable for
      arthroscopic access and view. Our view is that they are an ideal training model
      for arthroscopic meniscal repair, small joint arthroscopy and anterior cruciate
      ligament reconstruction.

PMID- 25776859
TI  - What is good for the circulation also lessens cancer risk.

PMID- 25776860
TI  - Bone-anchored hearing aids and unilateral sensorineural hearing loss: why do
      patients reject them?
AB  - OBJECTIVES: This study aimed to report the bone-anchored hearing aid uptake and
      the reasons for their rejection by unilateral sensorineural deafness patients.
      METHODS: A retrospective review of 90 consecutive unilateral sensorineural
      deafness patients referred to the Greater Manchester Bone-Anchored Hearing Aid
      Programme between September 2008 and August 2011 was performed. RESULTS: In all,
      79 (87.8 per cent) were deemed audiologically suitable: 24 (30.3 per cent)
      eventually had a bone-anchored hearing aid implanted and 55 (69.6 per cent)
      patients declined. Of those who declined, 26 (47.3 per cent) cited perceived
      limited benefits, 18 (32.7 per cent) cited reservations regarding surgery, 13
      (23.6 per cent) preferred a wireless contralateral routing of sound device and 12
      (21.8 per cent) cited cosmetic reasons. In all, 32 (40.5 per cent) suitable
      patients eventually chose the wireless contralateral routing of sound device.
      CONCLUSION: The uptake rate was 30 per cent for audiologically suitable patients.
      Almost half of suitable patients did not perceive a sufficient benefit to proceed
      to device implantation and a significant proportion rejected it. It is therefore
      important that clinicians do not to rush to implant all unilateral sensorineural
      hearing loss patients with a bone-anchored hearing aid.

PMID- 25776865
TI  - Graphene/Si-quantum-dot heterojunction diodes showing high photosensitivity
      compatible with quantum confinement effect.
AB  - Graphene/Si quantum dot (QD) heterojunction diodes are reported for the first
      time. The photoresponse, very sensitive to variations in the size of the QDs as
      well as in the doping concentration of graphene and consistent with the quantum
      confinement effect, is remarkably enhanced in the near-ultraviolet range compared
      to commercially available bulk-Si photodetectors. The photoresponse proves to be
      dominated by the carriertunneling mechanism.

PMID- 25776867
TI  - The taste system of small fish species.
AB  - Small fish species such as the zebrafish (Danio rerio) and medaka fish (Oryzias
      latipes) are advantageous animal models and have been used as model organisms in
      many research areas. However, they have not been utilized for studying the taste
      system, primarily because of a dearth of molecular biological knowledge.
      Quantitative methods for analyzing the taste preferences of fish species have
      also been lacking. Recent progress of the fish genome project has enabled the
      elucidation of the molecular mechanisms of taste sensation. Taste receptors and a
      number of signal transduction molecules have been identified. Additionally, the
      development of quantitative methods of feeding using fluorescently labeled
      artificial foods has demonstrated taste preferences in small fish species.
      Comparisons between these results in fish and reports on mammals have proposed a
      general logic and evolution of vertebrate taste systems. Analysis on the
      transsynaptic tracer-expressing transgenic medaka fish also suggests the
      usefulness of small fish in the research of neural circuits for taste. 

PMID- 25776868
TI  - Treatment with IL-10 producing B cells in combination with E2 ameliorates EAE
      severity and decreases CNS inflammation in B cell-deficient mice.
AB  - Clinical improvement during pregnancy in multiple sclerosis (MS) patients
      suggests that sex hormones exert potent regulatory effects on autoimmune
      function. Our previous studies demonstrated that estrogen- (17beta-estradiol; E2)
      mediated protection against experimental autoimmune encephalomyelitis (EAE), a
      mouse model for MS, hinges on the B cells, leading to elevated numbers of IL-10
      secreting CD1d(hi)CD5(+) B regulatory cells (Bregs) in wild type mice. Our data
      show that co-administration of E2 and IL-10(+) B cells ameliorates EAE disease
      severity and limits CNS infiltrating leukocytes in B cell deficient mice.
      Additionally, treatment with E2 and Bregs reduces demyelination and dramatically
      decreases the proportion of CD11b(+)CD45(hi) activated microglia/macrophages
      found in the CNS of immunized animals compared to vehicle, E2 or Breg cells
      alone. Furthermore, mice given E2 and Bregs exhibit increased numbers of
      peripheral programmed death-1 positive CD4(+)Foxp3(+) regulatory T cells (Tregs)
      and up-regulation of programmed death receptor-ligand-1 and CD80 expression on
      monocytes. Our study suggests IL-10 producing Bregs have powerful therapeutic
      potential as an agent against EAE when augmented with E2 treatment. 

PMID- 25776869
TI  - Sex Differences and Impact of Body Mass Index on the Time Course of Knee Range of
      Motion, Knee Strength, and Gait Speed After Total Knee Arthroplasty.
AB  - OBJECTIVE: Quadriceps strength deficits and gait speed limitations remain
      significant issues after total knee arthroplasty (TKA), yet detailed longitudinal
      data characterizing these measures and their predictors are limited. This study
      aimed to describe the time course of knee range of motion, quadriceps strength,
      and gait speed post-TKA, and to assess whether sex and body mass index (BMI)
      influenced the time recovery of these measures. METHODS: A total of 1,025
      patients (mean +/- SD age 67 +/- 8 years) undergoing primary TKA participated. At
      4-, 8-, 12-, and 16-weeks postsurgery, knee range of motion, quadriceps strength,
      and gait speed were quantified. The associations of the knee and gait measures
      profile over time with sex and BMI were assessed using generalized least squares
      modeling. RESULTS: The various knee and gait measures improved nonlinearly over
      time, with substantial improvements observed in the first 8-10 weeks postsurgery.
      Sex and BMI influenced the time course of quadriceps strength (P < 0.001 for all
      interactions): improvements in quadriceps strength over time were slower in women
      and in patients with higher BMI. Post-TKA gait speed was consistently lower in
      women than in men, while BMI was negatively and nonlinearly related to gait
      speed. CONCLUSION: Although the various knee and gait measures improved over
      time, women and patients with higher BMI had poorer functional outcomes. The
      present study highlights the need for a mechanistic understanding of the results
      and targeted management of these patient subgroups.

PMID- 25776870
TI  - A genome-wide study of inherited deletions identified two regions associated with
      nonsyndromic isolated oral clefts.
AB  - BACKGROUND: DNA copy number variants play an important part in the development of
      common birth defects such as oral clefts. Individual patients with multiple birth
      defects (including oral clefts) have been shown to carry small and large
      chromosomal deletions. METHODS: We investigated the role of polymorphic copy
      number deletions by comparing transmission rates of deletions from parents to
      offspring in case-parent trios of European ancestry ascertained through a cleft
      proband with trios ascertained through a normal offspring. DNA copy numbers in
      trios were called using the joint hidden Markov model in the freely available
      PennCNV software. All statistical analyses were performed using Bioconductor
      tools in the open source environment R. RESULTS: We identified a 67 kb region in
      the gene MGAM on chromosome 7q34, and a 206 kb region overlapping genes ADAM3A
      and ADAM5 on chromosome 8p11, where deletions are more frequently transmitted to
      cleft offspring than control offspring. CONCLUSIONS: These genes or nearby
      regulatory elements may be involved in the etiology of oral clefts.

PMID- 25776871
TI  - Engineering biomimetic materials for islet transplantation.
AB  - A closed-loop system that provides both the sensing of glucose and the
      appropriate dosage of insulin could dramatically improve treatment options for
      insulin-dependent diabetics. The intrahepatic implantation of allogeneic islets
      has the potential to provide this intimate control, by transplanting the very
      cells that have this inherent sensing and secretion capacity. Limiting islet
      transplantation, however, is the significant loss and dysfunction of islets
      following implantation, due to the poor engraftment environment and significant
      immunological attack. In this review, we outline approaches that seek to address
      these challenges via engineering biomimetic materials. These materials can serve
      to mimic natural processes that work toward improving engraftment, minimizing
      inflammation, and directing immunological responses. Biomimetic materials can
      serve to house cells, recapitulate native microenvironments, release therapeutic
      agents in a physiological manner, and/or present agents to direct cells towards
      desired responses. By integrating these approaches, superior platforms capable of
      improving long-term engraftment and acceptance of transplanted islets are on the
      horizon. 

PMID- 25776872
TI  - An optimized transversely isotropic, hyper-poro-viscoelastic finite element model
      of the meniscus to evaluate mechanical degradation following traumatic loading.
AB  - Inverse finite element (FE) analysis is an effective method to predict material
      behavior, evaluate mechanical properties, and study differences in biological
      tissue function. The meniscus plays a key role in load distribution within the
      knee joint and meniscal degradation is commonly associated with the onset of
      osteoarthritis. In the current study, a novel transversely isotropic hyper-poro
      viscoelastic constitutive formulation was incorporated in a FE model to evaluate
      changes in meniscal material properties following tibiofemoral joint impact. A
      non-linear optimization scheme was used to fit the model output to indentation
      relaxation experimental data. This study is the first to investigate rate of
      relaxation in healthy versus impacted menisci. Stiffness was found to be
      decreased (p=0.003), while the rate of tissue relaxation increased (p=0.010) at
      twelve weeks post impact. Total amount of relaxation, however, did not change in
      the impacted tissue (p=0.513). 

PMID- 25776886
TI  - Rapid-onset obesity with hypothalamic dysfunction, hypoventilation, and autonomic
      dysregulation (ROHHAD): Response to ventilatory challenges.
AB  - Hypoventilation is a defining feature of Rapid-onset Obesity with Hypothalamic
      dysfunction, Hypoventilation and Autonomic Dysregulation (ROHHAD), a rare
      respiratory and autonomic disorder. This chronic hypoventilation has been
      explained as the result of dysfunctional chemosensory control circuits, possibly
      affecting peripheral afferent input, central integration, or efferent motor
      control. However, chemosensory function has never been quantified in a cohort of
      ROHHAD patients. Therefore, the purpose of this study was to assess the response
      to awake ventilatory challenge testing in children and adolescents with ROHHAD.
      The ventilatory, cardiovascular and cerebrovascular responses in 25 distinct
      comprehensive physiological recordings from seven unique ROHHAD patients to three
      different gas mixtures were analyzed at breath-to-breath and beat-to-beat
      resolution as absolute measures, as change from baseline, or with derived
      metrics. Physiologic measures were recorded during a 3-min baseline period of
      room air, a 3-min gas exposure (of 100% O2; 95% O2, 5% CO2; or 14% O2, 7% CO2
      balanced with N2), and a 3-min recovery period. An additional hypoxic challenge
      was conducted which consisted of either five or seven tidal breaths of 100% N2.
      While ROHHAD cases showed a diminished VT and inspiratory drive response to
      hypoxic hypercapnia and absent behavioral awareness of the physiologic
      compromise, most ventilatory, cardiovascular, and cerebrovascular measures were
      similar to those of previously published controls using an identical protocol,
      suggesting a mild chemosensory deficit. Nonetheless, the high mortality rate,
      comorbidity and physiological fragility of patients with ROHHAD demand continued
      clinical vigilance.

PMID- 25776887
TI  - Curcumin Binding to Beta Amyloid: A Computational Study.
AB  - Curcumin, a chemical constituent present in the spice turmeric, is known to
      prevent the aggregation of amyloid peptide implicated in the pathophysiology of
      Alzheimer's disease. While curcumin is known to bind directly to various amyloid
      aggregates, no systematic investigations have been carried out to understand its
      ability to bind to the amyloid aggregates including oligomers and fibrils. In
      this study, we constructed computational models of (i) Abeta hexapeptide (16)
      KLVFFA(21) octamer steric-zipper beta-sheet assembly and (ii) full-length Abeta
      fibril beta-sheet assembly. Curcumin binding in these models was evaluated by
      molecular docking and molecular dynamics (MD) simulation studies. In both the
      models, curcumin was oriented in a linear extended conformation parallel to fiber
      axis and exhibited better stability in the Abeta hexapeptide (16) KLVFFA(21)
      octamer steric-zipper model (Ebinding  = -10.05 kcal/mol) compared to full-length
      Abeta fibril model (Ebinding  = -3.47 kcal/mol). Analysis of MD trajectories of
      curcumin bound to full-length Abeta fibril shows good stability with minimum
      Calpha-atom RMSD shifts. Interestingly, curcumin binding led to marked
      fluctuations in the (14) HQKLVFFA(21) region that constitute the fibril spine
      with RMSF values ranging from 1.4 to 3.6 A. These results show that curcumin
      binding to Abeta shifts the equilibrium in the aggregation pathway by promoting
      the formation of non-toxic aggregates. 

PMID- 25776888
TI  - Identification of O-glycan Structures from Chicken Intestinal Mucins Provides
      Insight into Campylobactor jejuni Pathogenicity.
AB  - The Gram-negative bacteria Campylobactor jejuni is the primary bacteria
      responsible for food poisoning in industrialized countries, and acute diarrheal
      illness is a leading cause of mortality among children in developing countries.
      C. jejuni are commensal in chickens. They are particularly abundant in the caecal
      crypts, and poultry products are commonly infected as a result of cross
      contamination during processing. The interactions between C. jejuni and chicken
      intestinal tissues as well as the pathogenic molecular mechanisms of colonization
      in humans are unknown, but identifying these factors could provide potential
      targets to reduce the incidence of campylobacteriosis. Recently, purified chicken
      intestinal mucin was shown to attenuate adherence and invasion of C. jejuni in
      the human colorectal adenocarcinoma cell line HCT-8 in vitro, and this effect was
      attributed to mucin O-glycosylation. Mucins from different regions of the chicken
      intestine inhibited C. jejuni binding and internalization differentially, with
      large intestine>small intestine>caecum. Here, we use LC-MS to perform a detailed
      structural analysis of O-glycans released from mucins purified from chicken large
      intestine, small intestine, and caecum. The O-glycans identified were abundantly
      sulfated compared with the human intestines, and sulfate moieties were present
      throughout the chicken intestinal tract. Interestingly, alpha 1-2 linked fucose
      residues, which have a high binding affinity to C. jejuni, were identified in the
      small and large intestines. Additionally, N-glycolylneuraminic/N-acetylneuraminic
      acid containing structures present as Sd(a)-like epitopes were identified in
      large intestine samples but not small intestine or caecum. O-glycan structural
      characterization of chicken intestinal mucins provides insights into adherence
      and invasion properties of C. jejuni, and may offer prospective candidate
      molecules aimed at reducing the incidence of infection. 

PMID- 25776889
TI  - The Drosophila Helicase Maleless (MLE) is Implicated in Functions Distinct From
      its Role in Dosage Compensation.
AB  - Helicases are ubiquitous enzymes that unwind or remodel single or double-stranded
      nucleic acids, and that participate in a vast array of metabolic pathways. The
      ATP-dependent DEXH-box RNA/DNA helicase MLE was first identified as a core member
      of the chromatin remodeling MSL complex, responsible for dosage compensation in
      Drosophila males. Although this complex does not assemble in females, MLE is
      present. Given the multiplicity of functions attributed to its mammalian ortholog
      RNA helicase A, we have carried out an analysis for the purpose of determining
      whether MLE displays the same diversity. We have identified a number of different
      proteins that associate with MLE, implicating its role in specific pathways. We
      have documented this association in selected examples that include the
      spliceosome complex, heterogeneous Nuclear Ribonucleoproteins involved in RNA
      Processing and in Heterochromatin Protein 1 deposition, and the NuRD complex. 

PMID- 25776890
TI  - Targeted-bisulfite sequence analysis of the methylation of CpG islands in genes
      encoding PNPLA3, SAMM50, and PARVB of patients with non-alcoholic fatty liver
      disease.
AB  - BACKGROUND & AIMS: The pathogenesis of non-alcoholic fatty liver disease (NAFLD)
      is affected by epigenetic factors as well as by genetic variation. METHODS: We
      performed targeted-bisulfite sequencing to determine the levels of DNA
      methylation of 4 CpG islands (CpG99, CpG71, CpG26, and CpG101) in the regulatory
      regions of PNPLA3, SAMM50, PARVB variant 1, and PARVB variant 2, respectively. We
      compared the levels of methylation of DNA in the livers of the first and second
      sets of patients with mild (fibrosis stages 0 and 1) or advanced (fibrosis stages
      2 to 4) NAFLD and in those of patients with mild (F0 to F2) or advanced (F3 and
      F4) chronic hepatitis C infection. The hepatic mRNA levels of PNPLA3, SAMM50, and
      PARVB were measured using qPCR. RESULTS: CpG26, which resides in the regulatory
      region of PARVB variant 1, was markedly hypomethylated in the livers of patients
      with advanced NAFLD. Conversely, CpG99 in the regulatory region of PNPLA3 was
      substantially hypermethylated in these patients. These differences in DNA
      methylation were replicated in a second set of patients with NAFLD or chronic
      hepatitis C. PNPLA3 mRNA levels in the liver of the same section of a biopsy
      specimen used for genomic DNA preparation were lower in patients with advanced
      NAFLD compared with those with mild NAFLD and correlated inversely with CpG99
      methylation in liver DNA. Moreover, the levels of CpG99 methylation and PNPLA3
      mRNA were affected by the rs738409 genotype. CONCLUSIONS: Hypomethylation of
      CpG26 and hypermethylation of CpG99 may contribute to the severity of fibrosis in
      patients with NAFLD or chronic hepatitis C infection.

PMID- 25776892
TI  - Complementary effects of torrefaction and co-pelletization: Energy consumption
      and characteristics of pellets.
AB  - In this study, complementary of torrefaction and co-pelletization for biomass
      pellets production was investigated. Two kinds of biomass materials were
      torrefied and mixed with oil cake for co-pelletization. The energy consumption
      during pelletization and pellet characteristics including moisture absorption,
      pellet density, pellet strength and combustion characteristic, were evaluated. It
      was shown that torrefaction improved the characteristics of pellets with high
      heating values, low moisture absorption and well combustion characteristic.
      Furthermore, co-pelletization between torrefied biomass and cater bean cake can
      reduce several negative effects of torrefaction such as high energy consumption,
      low pellet density and strength. The optimal conditions for energy consumption
      and pellet strength were torrefied at 270 degrees C and a blending with 15%
      castor bean cake for both biomass materials. The present study indicated that
      compelmentary performances of the torrefaction and co-pelletization with castor
      bean cake provide a promising alternative for fuel production from biomass and
      oil cake. 

PMID- 25776891
TI  - Hepatic steatosis and cardiovascular disease outcomes: An analysis of the
      Framingham Heart Study.
AB  - BACKGROUND & AIMS: Non-alcoholic fatty liver disease (NAFLD) is highly prevalent
      and is associated with development of metabolic disease including atherosclerotic
      cardiovascular disease (CVD). Our aim is to examine the association of hepatic
      steatosis with prevalent clinical and subclinical CVD outcomes in a large
      community-based sample, the Framingham Heart Study. METHODS: Hepatic steatosis
      was measured in 3529 participants using multidetector computed tomography
      scanning. Multivariable logistic regression was used to determine whether hepatic
      steatosis is associated with prevalent CVD adjusted for covariates. We also
      tested whether associations were independent of other metabolic diseases/traits.
      The primary clinical outcome was composite prevalent clinical CVD defined by
      prior non-fatal myocardial infarction, stroke, transient ischemic attack, heart
      failure, or peripheral arterial disease. Subclinical cardiovascular outcomes were
      coronary artery calcium (CAC) and abdominal artery calcium (AAC). RESULTS: 3014
      participants were included (50.5% women). There was a non-significant association
      of hepatic steatosis with clinical CVD (OR 1.14 [p=0.07]). Hepatic steatosis was
      associated with both CAC and AAC (OR 1.20 [p<0.001] and OR 1.16 [p<0.001],
      respectively). Associations persisted for CAC even when controlling for other
      risk factors/metabolic diseases, but for AAC, the associations became non
      significant after adjustment for visceral adipose tissue. The association between
      hepatic steatosis and AAC was stronger in men than in women (p sex
      interaction=0.022). CONCLUSION: There was a significant association of hepatic
      steatosis with subclinical CVD outcomes independent of many metabolic
      diseases/traits with a trend towards association between hepatic steatosis and
      clinical CVD outcomes. The association with AAC was stronger in men than in
      women.

PMID- 25776893
TI  - Mechanical milling and membrane separation for increased ethanol production
      during simultaneous saccharification and co-fermentation of rice straw by xylose
      fermenting Saccharomyces cerevisiae.
AB  - Mechanical milling and membrane separation were applied to simultaneous
      saccharification and co-fermentation from hydrothermally pretreated rice straw.
      Mechanical milling with minimized 4 cycles enabled 37.5+/-3.4gL(-1) and 45.3+/
      4.4gL(-1) of ethanol production after 48h by xylose-fermenting Saccharomyces
      cerevisiae from solid fractions (200 and 250gL(-1)) of pretreated rice straw with
      5 filter paper unitg-biomass(-1) cellulase (respectively, 77.3+/-7.1% and 74.7+/
      7.3% of theoretical ethanol yield). Use of a membrane-based process including
      nanofiltration and ultrafiltration increased the sugar concentrations in the
      liquid fraction of pretreated rice straw and addition of this liquid fraction to
      250gL(-1) solid fraction increased ethanol production to 52.0+/-0.4gL(-1) (73.8+/
      0.6% of theoretical ethanol yield). Mechanical milling was effective in
      increasing enzymatic hydrolysis of the solid fraction and membrane separation
      steps increased the ethanol titer during co-fermentation, leading to a proposal
      for combining these processes for ethanol production from whole rice straw. 

PMID- 25776894
TI  - Improving high carbon dioxide tolerance and carbon dioxide fixation capability of
      Chlorella sp. by adaptive laboratory evolution.
AB  - CO2 capture by microalgae is a promising method to reduce greenhouse gas
      emissions. It is critical to construct a highly efficient way to obtain a
      microalgal strain tolerant to high CO2 concentrations with high CO2 fixation
      capability. In this study, two evolved Chlorella sp. strains, AE10 and AE20 were
      obtained after 31 cycles of adaptive laboratory evolution (ALE) under 10% and 20%
      CO2, respectively. Both of them grew rapidly in 30% CO2 and the maximal biomass
      concentration of AE10 was 3.68+/-0.08g/L, which was 1.22 and 2.94 times to those
      of AE20 and original strain, respectively. The chlorophyll contents of AE10 and
      AE20 were significantly higher than those of the original one under 1-30% CO2.
      The influences of ALE process on biochemical compositions of Chlorella cells were
      also investigated. This study proved that ALE was an effective approach to
      improve high CO2 tolerance of Chlorella sp. 

PMID- 25776895
TI  - Psychological experience of patients 3 months after a stay in the intensive care
      unit: A descriptive and qualitative study.
AB  - PURPOSE: The purpose was to describe psychological experiences of patients 3
      months after a stay in the intensive care unit (ICU) using qualitative methods.
      METHODS: Twenty patients underwent clinical interview lasting 1 hour and
      completed the Impact of Event Scale-Revised and Hospital Anxiety and Depression
      questionnaires. All interviews were recorded and coded using thematic analysis.
      RESULTS: All patients (100%) reported that they could not remember their ICU
      stay; half reported confused memories (50%) or disorientation (50%). Negatives
      memories were also reported (20%-45%), namely, pain, distress, sleep
      difficulties, noise, fear, feeling of abandonment; 20% reported positive
      memories. At 3 months, for 10 (50%) of 20 patients, their ICU experience was
      characterized by anxiety; 3 (15%) of 20 presented posttraumatic stress disorder;
      7 (35%) of 20 reported a feeling of well-being with positive life changes. Well
      being seems to be associated with use of coping strategies, such as active
      coping, positive reframing, optimism, humor, acceptance, leisure activities, and
      family support. CONCLUSION: Our study highlights the need to investigate
      patients' memories of ICU and the coping strategies used by patients to improve
      their ICU experience. Our findings suggest that a systematic follow-up
      consultation after ICU discharge would be useful for monitoring of post-ICU
      psychological outcomes.

PMID- 25776896
TI  - Balancing care and teaching during clinical activities: 2 contexts, 2 strategies.
AB  - PURPOSE: The goal of this study was to better understand how clinical supervisors
      integrate teaching interactions with medical trainees into 2 types of clinical
      activities in the critical care setting: multidisciplinary rounds and medical
      crises. METHODS: We conducted a qualitative, observational study based on an
      ethnographic approach. We observed the teaching interactions among clinical
      supervisors and medical trainees during 12 multidisciplinary rounds and 74
      medical crises in 2 academic hospitals. Grounded theory methods (theoretical
      sampling and saturation, inductive thematic coding, and constant comparison) were
      used to analyze data. RESULTS: Two models of integration of teaching interactions
      into clinical activities are described: the in series model, typical of
      multidisciplinary rounds and characterized by well-structured learning bubbles
      uninterrupted by patient care, and the in parallel model, common during medical
      crises and involving multiple, short learning flashes intricately related to and
      frequently interrupted by patient care. By adopting a model over the other,
      supervisors appeared to adapt to 2 contexts that differed in terms of priority,
      supervisor's understanding of events, and social context of interactions. Each
      model presented complementary opportunities and limitations for learning.
      CONCLUSIONS: Modern views of medical apprenticeship and clinical teaching need to
      take into account the specific clinical context in which learning occurs.
      Teaching interactions that differ in structure and content in response to
      changing clinical circumstances could impact learning in unique ways. Learning
      outcomes resulting from different models of integration of teaching into clinical
      activities need to be further explored.

PMID- 25776897
TI  - Intravenous immunoglobulin improves sepsis-induced coagulopathy: A retrospective,
      single-center observational study.
AB  - INTRODUCTION: Inflammation and coagulation are closely interrelated processes in
      the pathogenesis of sepsis. This study aimed to determine whether intravenous
      immunoglobulin (IVIg) could improve the hyperinflammatory state and
      coagulation/fibrinolysis abnormalities in patients with sepsis. METHODS: Forty
      one patients with sepsis were included. Nineteen patients were treated with IVIg
      (IVIg group; 5.0 g daily for 3 days within 2 days after hospitalization), and 22
      patients were not (non-IVIg group). Inflammatory and coagulation/fibrinolysis
      molecular markers, Japanese Association for Acute Medicine disseminated
      intravascular coagulation score, and the Sequential Organ Failure Assessment
      score were evaluated in each group. RESULTS: On admission, patients in the IVIg
      group had a significantly more severe condition. In the IVIg group, after
      treatment, C-reactive protein, procalcitonin, and interleukin-6 levels
      significantly decreased relative to values on admission. Also, compared with
      admission, the various coagulation/fibrinolysis molecular markers decreased after
      treatment. Moreover, the Japanese Association for Acute Medicine disseminated
      intravascular coagulation score and the Sequential Organ Failure Assessment score
      also significantly decreased after treatment. In contrast, in the non-IVIg group,
      only interleukin-6 level and thrombin-antithrombin complex levels significantly
      decreased. The 28-day mortality rate of the IVIg group was approximately one
      third of the value of the non-IVIg group (IVIg: 5.3% vs non-IVIg: 18.2%).
      CONCLUSIONS: Intravenous immunoglobulin treatment significantly improved
      hemostatic abnormalities along with the hyperinflammatory state in patients with
      sepsis. Accordingly, IVIg treatment should be classified as an adjunctive therapy
      for patients complicated with sepsis-induced coagulopathy.

PMID- 25776898
TI  - Doppler-based renal resistive index for prediction of renal dysfunction
      reversibility: There are still some questions.

PMID- 25776899
TI  - Sphingosine-1-phosphate receptor 1 agonist SEW2871 prolongs heterotopic heart
      allograft survival in mice.
AB  - Sphingosine-1-phosphate (S1P) is a biologically active metabolite of plasma
      membrane sphingolipids that is essential for immune cell trafficking. Recent
      studies have revealed immunomodulatory functions of S1P and its receptors (S1PR1
      S1PR5) in many inflammatory conditions, such as asthma and autoimmunity. Here, we
      explore the efficacy of SEW2871, a selective S1PR1 agonist, in the prevention of
      acute allograft rejection in a murine cardiac transplantation model. Treatment of
      recipient mice with SEW2871 significantly prolongs cardiac allograft survival as
      compared to those recipients treated with control vehicle. The enhanced graft
      survival is associated with reduced circulating lymphocytes and allograft
      inflammatory cell infiltration. The cytokine analysis showed decreased allograft
      expression of TNF-alpha, IFN-gamma and IL-2 in the SEW2871-treated mice.
      Moreover, administration of SEW2871 increases the percentage of CD4(+) T
      regulatory cells and FoxP3 expression in spleen of allograft recipients.
      Therefore, SEW2871 plays a critical role in regulation of lymphocyte trafficking
      and development, which directly contributes to prolongation of the allograft
      survival. 

PMID- 25776900
TI  - Ethnopharmacological importance of medicinal flora from the district of Vehari,
      Punjab province, Pakistan.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Ethnopharmacological studies are important for
      the discovery of new drugs from reported indigenous flora. The current study was
      aimed to document medicinal flora and its therapeutic actions along with the
      relative importance in local health care system of the district of Vehari, Punjab
      province, Pakistan. MATERIALS AND METHOD: Rapid appraisal approach (RAA) and semi
      structured interviews were used along with the group meetings with herbalists,
      local inhabitants and landowners to collect the relevant data. RESULTS AND
      DISCUSSIONS: A total 77 medicinal plants belonging to 41 families disseminated
      among 71 genera were reported. Fabaceae was the predominant family over others
      with 9 reported medicinal plant species. Use frequency of leaves was at peak with
      30.12% followed by stem 24.62%, fruit 14.22%, flower 12.97%, seeds 12.13%, bark
      4.6% and pod 1.25%, in herbal preparations. Allium cepa exhibited the highest use
      value (0.90) while lowest use value (UV) was reflected by Aerva javanica (0.10).
      Documentation of various medicinal plants for the treatment of cancer, hepatitis
      and cardiac disorders is evidence in favor to highlight the value of medicinal
      flora. CONCLUSIONS: Unfortunately, no attention has been paid to this treasure in
      term of conservation and utilization in modern healthcare system, where these
      plants can be a best replacement of chemically synthesized drugs. It is also
      recommended that plants exhibiting high UV should be screened for detailed bio
      active phytochemicals.

PMID- 25776901
TI  - Mapping the landscape of cognitive development in children with epilepsy.
AB  - OBJECTIVE: Normal childhood development is defined by age-dependent improvement
      across cognitive abilities, including language, memory, psychomotor speed and
      executive function. Epilepsy is often associated with a global disruption in
      cognitive development, however, it is still largely unknown how epilepsy affects
      the overall organization of overlapping cognitive domains. The aim of the study
      was to evaluate how childhood epilepsy affects the developmental
      interrelationships between cognitive domains. METHODS: We performed a
      comprehensive assessment of neuropsychological function in 127 children with new
      onset epilepsy and 80 typically developing children matched for age, gender, and
      socio-demographic status. A cross-correlation matrix between the performances
      across multiple cognitive tests was used to assess the interrelationship between
      cognitive modalities for each group (patients and controls). A weighted network
      composed by the cognitive domains as nodes, and pair-wise domain correlation as
      links, was assessed using graph theory analyses, with focus on global network
      structure, network hubs and community structure. RESULTS: Normally developing
      children exhibited a cognitive network with well-defined modules, with verbal
      intelligence, reading and spelling skills occupying a central position in the
      developing network. Conversely, children with epilepsy demonstrated a less well
      organized network with less clear separation between modules, and relative
      isolation of measures of attention and executive function. CONCLUSION: Our
      findings demonstrate that childhood-onset epilepsy, even within its early course,
      is associated with an extensive disruption of cognitive neurodevelopmental
      organization. The approach used in this study may be useful to assess the
      effectiveness of future interventions aimed at mitigating the cognitive
      consequences of epilepsy.

PMID- 25776902
TI  - Contemporary trends in the use of primary repair for gastroschisis in surgical
      infants.
AB  - BACKGROUND: Gastroschisis is a newborn anomaly requiring emergent surgical
      intervention. We review our experience with gastroschisis to examine trends in
      contemporary surgical management. METHODS: Infants who underwent initial surgical
      management of gastroschisis from 1996 to 2014 at a pediatric hospital were
      reviewed. Closure techniques included primary fascial repair using suture or
      sutureless umbilical closure, and staged repair using sutured or spring-loaded
      silo (SLS). Data were separated into 3 clinical eras: pre-SLS (1996 to 2004), SLS
      (2005 to 2008), and umbilical closure (2009 to 2014). RESULTS: In the pre-SLS
      era, 60% (34/57) of infants with gastroschisis underwent primary repair. With the
      advent of SLS, there was a decrease in primary repair (15%, 10/68, P < .0001).
      Following introduction of sutureless umbilical closure, 61% (47/77) of infants
      have undergone primary repair. On multivariate regression, primary repair was
      associated with shorter intensive care unit stays (P < .001) and time to initiate
      enteral nutrition (P < .01). CONCLUSIONS: Following introduction of a less
      invasive technique for gastroschisis repair, most infants with gastroschisis were
      able to be repaired primarily. Primary repair should be considered in all babies
      with gastroschisis and favorable anatomy.

PMID- 25776903
TI  - Comparison of pencil beam-based homogeneous vs inhomogeneous target dose planning
      for stereotactic body radiotherapy of peripheral lung tumors through Monte Carlo
      based recalculation.
AB  - This study was conducted to ascertain whether homogeneous target dose planning is
      suitable for stereotactic body radiotherapy (SBRT) of peripheral lung cancer
      under appropriate breath-holding. For 20 peripheral lung tumors, paired dynamic
      conformal arc plans were generated by only adjusting the leaf margin to the
      planning target volume (PTV) edge for fulfilling the conditions such that the
      prescription isodose surface (IDS) encompassing exactly 95% of the PTV (PTV D95)
      corresponds to 95% and 80% IDS, normalized to 100% at the PTV isocenter under a
      pencil beam (PB) algorithm with radiologic path length correction. These plans
      were recalculated using the x-ray voxel Monte Carlo (XVMC) algorithm under
      otherwise identical conditions, and then compared. Lesions abutting the parietal
      pleura or not were defined as edge or island tumors, respectively, and the
      influences of the target volume and its location relative to the chest wall on
      the target dose were examined. The median (range) leaf margin required for the
      95% and 80% plans was 3.9 mm (1.3 to 5.0) and -1.2 mm (-1.8 to 0.1),
      respectively. Notably, the latter was significantly correlated negatively with
      PTV. In the 80% plans, the PTV D95 was slightly higher under XVMC, whereas the
      PTV D98 was significantly lower, irrespective of the dose calculation algorithm
      used. Other PTV and all gross tumor volume doses were significantly higher, while
      the lung doses outside the PTV were slightly lower. The target doses increased as
      a function of PTV and were significantly lower for island tumors than for edge
      tumors. In conclusion, inhomogeneous target dose planning using smaller leaf
      margin for a larger tumor volume was deemed suitable in ensuring more sufficient
      target dose while slightly reducing lung dose. In addition, more inhomogeneous
      target dose planning using <80% IDS (e.g., 70%) for PTV covering would be
      preferable for island tumors.

PMID- 25776904
TI  - Positron emission tomography imaging of human colon cancer xenografts in mice
      with [18F]fluorothymidine after TAS-102 treatment.
AB  - PURPOSE: TAS-102 is an orally administered anticancer agent composed of
      alpha,alpha,alpha-trifluorothymidine (FTD) and thymidine phosphorylase inhibitor
      (TPI). This study assessed 3'-deoxy-3'-[(18)F]fluorothymidine ([(18)F]FLT) uptake
      after TAS-102 administration. METHODS: The human colorectal carcinoma cell lines
      HCT116, HT29, HCT8 and SW620 were exposed to FTD for 2 h, further incubated for
      0, 2 and 24 h, and assayed for [(3)H]FLT uptake, nucleoside transport, thymidine
      kinase 1 (TK1) expression and TK1 activity. Static and 2-h dynamic [(18)F]FLT
      positron emission tomography (PET) was performed in mice bearing HT29 or SW620
      tumours orally administered with vehicle or TAS-102. RESULTS: FTD decreased the
      viability of all cell lines, whereas increased [(3)H]FLT uptake (P < 0.05).
      Increased nucleoside transport and/or TK1 expression were observed 24 h after
      FTD, but not in 0-2 h. Static [(18)F]FLT PET in mice bearing HT29 tumours showed
      accumulation of [(18)F]FLT in tumours 1 h (day 1) after TAS-102. Two-hour dynamic
      PET in mice bearing SW620 tumours showed increased influx constant and volume of
      distribution of phosphorylated [(18)F]FLT on days 1 and 8 (P < 0.05) after TAS
      102 with decreased dephosphorylation on day 1 (P < 0.001). Ex vivo studies showed
      that SW620 tumours after TAS-102 had higher TK1 expression than those with
      vehicle on days 8 and 15. CONCLUSION: TAS-102 administration induces an increase
      in [(18)F]FLT uptake. Mechanisms may involve decreased dephosphorylation of
      [(18)F]FLT phosphate early after TAS-102 administration. Increased TK1 expression
      and/or nucleoside transporter may be related to increased [(18)F]FLT uptake at a
      later time. [(18)F]FLT PET has a potential to assess the pharmacodynamics of TAS
      102 in cancer patients.

PMID- 25776905
TI  - Plasma pharmacokinetics of the indenoisoquinoline topoisomerase I inhibitor, NSC
      743400, in rats and dogs.
AB  - PURPOSE: NSC 743400 is a novel synthetic indenoisoquinoline analog under
      development as an anticancer agent. It is a potent topoisomerase I inhibitor with
      potential therapeutic advantages over FDA-approved camptothecin derivatives. In
      preparation for clinical development of NSC 743400, we determined the
      pharmacokinetics after administration to rats and dogs. METHODS: NSC 743400 was
      administered intravenously at a dose of 12 or 24 mg/m(2) to rats (single bolus)
      or 10, 50, 100, 215, 430, or 646 mg/m(2) (intravenous infusion) or 860 or 1720
      mg/m(2) (orally) to dogs. RESULTS: Intravenously administered NSC 743400 was
      eliminated from both species with an estimated t 1/2 of 2-5 h in rat and 6-14 h
      in dog. Elimination t 1/2 increased with dose in dog. Area under the plasma
      concentration-versus-time curve (AUC) was comparable in both species, at about
      300-400 h ng/mL for the approximately 10 mg/m(2) dose groups. Overall, AUC values
      increased proportionally with dose for both species but had evidence of more than
      proportional exposure at the highest doses. Oral dosing resulted in variable drug
      absorption. CONCLUSIONS: The pharmacokinetic data were used to plan first-in
      human clinical trials.

PMID- 25776906
TI  - Vascular endothelial growth factor receptor tyrosine kinase inhibitor (VEGFR-TKI)
      rechallenge for patients with metastatic renal cell carcinoma after treatment
      failure using both VEGFR-TKI and mTOR inhibitor.
AB  - PURPOSE: To assess the efficacy of vascular endothelial growth factor receptor
      tyrosine kinase inhibitor (VEGFR-TKI) rechallenge for metastatic renal cell
      carcinoma (mRCC) patients and to identify predictive factors for increased
      progression-free survival (PFS) or overall survival (OS). METHODS: The
      clinicopathological features, outcomes, and prognostic factors of mRCC patients
      who were treated with VEGFR-TKI after treatment failure using both VEGFR-TKIs and
      mTOR inhibitors (mTORi) were reviewed. RESULTS: A total of 29 eligible patients
      were included. Five (17 %) patients achieved partial response (PR) with a median
      response duration of 9.5 months (95 % CI 5.7-13.4 months), and additional 16
      patients (55 %) achieved stable disease. With a median follow-up period of 19.2
      months (95 % CI 18.9-19.6 months), the median PFS and OS were 3.0 months (95 % CI
      1.1-4.9 months) and 4.9 months (95 % CI 2.9-6.8 months), respectively. In
      univariate analysis, the best response to first-line VEGFR-TKI (PR vs. non-PR, p
      < 0.001) and time to rechallenge (TTR, <=12 months vs. between 12 and 24 months
      vs. >24 months, p = 0.005) were identified as predictive factors for longer PFS
      on VEGFR-TKI rechallenge. In addition, an MSKCC risk group (intermediate- vs.
      poor-risk group, p = 0.027), better response at first-line VEGFR-TKI (PR vs. non
      PR, p = 0.003), and TTR (<=12 months vs. between 12 and 24 months vs. >24 months,
      p = 0.026) were identified as prognostic factors for longer OS. CONCLUSIONS:
      VEGFR-TKI rechallenge may be a viable option for select metastatic RCC patients
      who fail both VEGFR-TKI and mTORi therapies.

PMID- 25776908
TI  - Perioperative Complications following Artificial Urinary Sphincter Placement.
AB  - PURPOSE: We evaluated perioperative complications in patients undergoing primary
      artificial urinary sphincter placement and the potential impact of these
      complications on device outcomes. MATERIALS AND METHODS: During the 2-year period
      from 2012 to 2014 we retrospectively evaluated the outcomes of 197 consecutive
      artificial urinary sphincter implantation procedures performed at our institution
      for post-prostatectomy incontinence. Of these cases 100 that were primary
      implantations comprise the study cohort. Perioperative complications, defined as
      those occurring within 6 weeks postoperatively, were classified by the Clavien
      Dindo classification. After office evaluation at 6 weeks patients were followed
      for symptoms. Patient followup was obtained through office examination and
      telephone correspondence. RESULTS: Patients undergoing primary artificial urinary
      sphincter implantation had a median age of 71.5 years (IQR 66, 76). The overall
      rate of any complication (Clavien I-V) within 6 weeks of surgery was 35%,
      including urinary retention in 31% of cases, cellulitis in 1%, device infection
      in 2% and urethral erosion in 2%. No significant differences in pertinent
      clinical comorbidities such as age (p = 0.69), hypertension (p = 0.95), coronary
      artery disease (p = 0.57), diabetes mellitus (p = 0.17), body mass index (p =
      0.47), prior pelvic radiation therapy (p = 0.45), prior urethral sling placement
      (p = 0.91) or transcorporeal urethral cuff placement (p = 0.22) were found
      between patients with and without complications. Median followup was similar
      between those with and without postoperative urinary retention (p = 0.14).
      Postoperative urinary retention was associated with adverse 6-month device
      survival (76% vs 89%, p = 0.04). CONCLUSIONS: The most common complication of
      artificial urinary sphincter placement is urinary retention. Serious adverse
      events following artificial urinary sphincter placement are rare. Postoperative
      urinary retention is associated with adverse short-term device survival rates.

PMID- 25776909
TI  - Can Bladder Wall Thickness Predict Videourodynamic Findings in Children with
      Spina Bifida?
AB  - PURPOSE: We investigated whether bladder wall thickness measured at specifically
      defined bladder volumes could predict videourodynamic findings in children with
      spina bifida. MATERIALS AND METHODS: We prospectively investigated patients with
      spina bifida on intermittent catheterization who underwent ultrasound examination
      simultaneously with videourodynamics. We evaluated the association between
      bladder wall thickness measured at maximum cystometric capacity and parameters
      including age, maximum detrusor pressure during filling or at leak and bladder
      compliance. Differences in bladder wall thickness measured at each percent
      maximum cystometric capacity were compared between patients with and without
      unfavorable videourodynamic findings. Maximum detrusor pressure 40 cm H2O or
      greater during filling or at leak, bladder compliance less than 10 ml/cm H2O,
      detrusor overactivity, bladder trabeculation and vesicoureteral reflux were
      defined as unfavorable videourodynamic findings. RESULTS: A total of 23 males and
      30 females with spina bifida (median age 7.8 years) underwent measurement of
      bladder wall thickness at maximum cystometric capacity. Mean +/- SD bladder wall
      thickness measured at maximum cystometric capacity was 1.7 +/- 0.5 mm. Only age
      had a weak correlation with bladder wall thickness measured at maximum
      cystometric capacity (p <0.05). In 31 patients bladder wall thickness was
      measured at each percent maximum cystometric capacity. Regarding unfavorable
      videourodynamic findings, there were no significant differences in bladder wall
      thickness measured at each percent maximum cystometric capacity, except for
      bladder trabeculation. CONCLUSIONS: Even if bladder wall thickness is measured at
      specifically defined bladder volumes, it cannot predict videourodynamic findings
      other than bladder trabeculation in children with spina bifida.

PMID- 25776910
TI  - Do Montelukast Sodium and N-Acetylcysteine Have a Nephroprotective Effect on
      Unilateral Ureteral Obstruction? A Placebo Controlled Trial in a Rat Model.
AB  - PURPOSE: We assessed the nephroprotective effects of montelukast sodium and N
      acetylcysteine on secondary renal damage due to unilateral ureteral obstruction
      in a rat model. MATERIALS AND METHODS: In this study 30 Wistar albino male rats
      were randomized into 3 groups, including placebo, N-acetylcysteine and
      montelukast sodium. Three rats served as the control group. The left ureter of
      the rats was sutured with 4-zero polyglactin sutures. Medications were given 3
      days before obstruction and continued for 15 days. Dimercaptosuccinic acid renal
      scintigraphy was performed before obstruction and on day 15. Rats were sacrificed
      on day 15 and histopathological examinations were done. We biochemically assessed
      oxidative stress markers (myeloperoxidase and malondialdehyde), sulfhydryl and
      total nitrite for lipid peroxidation, oxidative protein damage and antioxidant
      levels, respectively. RESULTS: On pathological examination inflammation and
      tubular epithelial damage in the N-acetylcysteine and montelukast sodium groups
      were less than in the placebo group (p <0.05). No difference was seen in normal
      kidneys. Myeloperoxidase, malondialdehyde and total nitrite levels in the N
      acetylcysteine group, and myeloperoxidase and malondialdehyde levels in the
      montelukast sodium group were lower than in the placebo group (p <0.05). No
      statistical difference was seen in sulfhydryl levels (p >0.05) or among the N
      acetylcysteine, montelukast sodium and placebo groups on scintigraphy (p >0.05).
      No pathological, chemical and scintigraphic differences were seen among the N
      acetylcysteine, montelukast sodium and sham treated groups (p >0.05).
      CONCLUSIONS: N-acetylcysteine and montelukast sodium have a protective effect
      against obstructive damage of the kidney. However, further investigations are
      needed.

PMID- 25776911
TI  - Prostatic-type epithelial polyp of the urethra.

PMID- 25776914
TI  - Erdheim-Chester disease.

PMID- 25776913
TI  - Mechanisms of Visceral Organ Crosstalk: Importance of Alterations in Permeability
      in Rodent Models.
AB  - PURPOSE: The pathophysiology of painful bladder syndrome is poorly understood.
      However, there is evidence of female predominance and comorbidity with irritable
      bowel syndrome. Our hypothesis is that cross-sensitization between bladder and
      colon is due to altered permeability in 1 organ, which affects the other organ.
      MATERIALS AND METHODS: Experiments were performed in anesthetized, ovariectomized
      female rats. In separate groups protamine sulfate was infused in the bladder or
      trinitrobenzene sulfonic acid was infused in the colon. Untreated rats served as
      controls. Bladder and colonic tissue were harvested from all rats 1, 3 and 5 days
      after treatment. Permeability was assessed in vitro in Ussing chambers by
      measuring transepithelial electrical resistance and macromolecular flux of
      fluorescein isothiocyanate-dextran. RESULTS: Exposing the bladder to protamine
      sulfate induced a significant decrease in bladder transepithelial electrical
      resistance and an increase in the translocation of fluorescein isothiocyanate
      across the tissue compared to controls at 1 and 3 days (p <0.05). Colonic tissue
      from rats with enhanced bladder permeability showed a significant decrease in
      transepithelial electrical resistance and increase in fluorescein isothiocyanate
      compared to untreated controls at all time points (p <0.05). Conversely when
      colonic permeability was increased with trinitrobenzene sulfonic acid, we
      observed an increase in bladder permeability in the absence of any changes to the
      bladder urothelium. CONCLUSIONS: Changes in epithelial permeability may represent
      a novel mechanism for visceral organ crosstalk. It may explain the overlapping
      symptomology of painful bladder syndrome and irritable bowel syndrome.

PMID- 25776915
TI  - High rate manure supernatant digestion.
AB  - The study shows that high rate anaerobic digestion may be an efficient way to
      obtain sustainable energy recovery from slurries such as pig manure. High process
      capacity and robustness to 5% daily load increases are observed in the 370 mL
      sludge bed AD reactors investigated. The supernatant from partly settled, stored
      pig manure was fed at rates giving hydraulic retention times, HRT, gradually
      decreased from 42 to 1.7 h imposing a maximum organic load of 400 g COD L(-1)
      reactor d(-1). The reactors reached a biogas production rate of 97 g COD L(-1)
      reactor d(-1) at the highest load at which process stress signs were apparent.
      The yield was ~0.47 g COD methane g(-1) CODT feed at HRT above 17 h, gradually
      decreasing to 0.24 at the lowest HRT (0.166 NL CH4 g(-1) CODT feed decreasing to
      0.086). Reactor pH was innately stable at 8.0 +/- 0.1 at all HRTs with alkalinity
      between 9 and 11 g L(-1). The first stress symptom occurred as reduced methane
      yield when HRT dropped below 17 h. When HRT dropped below 4 h the propionate
      removal stopped. The yield from acetate removal was constant at 0.17 g COD
      acetate removed per g CODT substrate. This robust methanogenesis implies that pig
      manure supernatant, and probably other similar slurries, can be digested for
      methane production in compact and effective sludge bed reactors. Denaturing
      gradient gel electrophoresis (DGGE) analysis indicated a relatively fast
      adaptation of the microbial communities to manure and implies that non-adapted
      granular sludge can be used to start such sludge bed bioreactors. 

PMID- 25776916
TI  - Enhancing combined biological nitrogen and phosphorus removal from wastewater by
      applying mechanically disintegrated excess sludge.
AB  - The goal of the study was to evaluate the possibility of applying disintegrated
      excess sludge as a source of organic carbon to enhance biological nitrogen and
      phosphorus removal. The experiment, performed in a sequencing batch reactor,
      consisted of two two-month series, without and with applying mechanically
      disintegrated excess sludge, respectively. The effects on carbon, nitrogen and
      phosphorus removal were observed. It was shown that the method allows enhancement
      of combined nitrogen and phosphorus removal. After using disintegrated sludge,
      denitrification effectiveness increased from 49.2 +/- 6.8% to 76.2 +/- 2.3%,
      which resulted in a decline in the NOx-N concentration in the effluent from the
      SBR by an average of 21.4 mg NOx-N/L. Effectiveness of biological phosphorus
      removal increased from 28.1 +/- 11.3% to 96.2 +/- 2.5%, thus resulting in a drop
      in the [Formula: see text] concentration in the effluent by, on average, 6.05 mg
      PO4(3-)-P/L. The application of disintegrated sludge did not deteriorate effluent
      quality in terms of COD and NH4(+)-N. The concentration of NH4(+)-N in both
      series averaged 0.16 +/- 0.11 mg NH4(+)-N/L, and the concentration of COD was
      15.36 +/- 3.54 mg O2/L.

PMID- 25776917
TI  - Representative input load of antibiotics to WWTPs: Predictive accuracy and
      determination of a required sampling quantity.
AB  - Predicting the input loads of antibiotics to wastewater treatment plants (WWTP)
      using certain input data (e.g. prescriptions) is a reasonable method if no
      analytical data is available. Besides the spatiotemporal uncertainties of the
      projection itself, only a few studies exist to confirm the suitability of
      required excretion data from literature. Prescription data with a comparatively
      high resolution and a sampling campaign covering 15 months were used to answer
      the question of applicability of the prediction approach. As a result,
      macrolides, sulfamethoxazole and trimethoprim were almost fully recovered close
      to 100% of the expected input loads. Nearly all substances of the beta-lactam
      family exhibit high elimination rates during the wastewater transport in the
      sewer system with a low recovery rate at the WWTP. The measured input loads of
      cefuroxime, ciprofloxacin and levofloxacin fluctuated greatly through the year
      which was not obvious from relatively constant prescribed amounts. The latter
      substances are an example that available data are not per se sufficient to
      monitor the actual release into the environment. Furthermore, the extensive data
      pool of this study was used to calculate the necessary number of samples to
      determine a representative annual mean load to the WWTP. For antibiotics with low
      seasonality and low input scattering a minimum of about 10 samples is required.
      In the case of antibiotics exhibiting fluctuating input loads 30 to 40 evenly
      distributed samples are necessary for a representative input determination. As a
      high level estimate, a minimum number of 20-40 samples per year is proposed to
      reasonably estimate a representative annual input load of antibiotics and other
      micropollutants. 

PMID- 25776918
TI  - Impacts of hydrophilic colanic acid on bacterial attachment to microfiltration
      membranes and subsequent membrane biofouling.
AB  - In order to examine the interactions between physicochemical properties of
      specific extracellular polymeric substances (EPS) and membrane biofouling, we
      investigated the impacts of hydrophilic colanic acid, as a model extracellular
      polysaccharide component, on initial bacterial attachment to different
      microfiltration (MF) membranes and membrane biofouling by using Escherichia coli
      strains producing different amounts of colanic acid. In a newly designed
      microtiter plate assay, the bacterial attachment by an E. coli strain RcsF(+),
      which produces massive amounts of colanic acid, decreased only to a hydrophobic
      membrane because the colanic acid made cell surfaces more hydrophilic, resulting
      in low cell attachment to hydrophobic membranes. The bench-scale cross-flow
      filtration tests followed by filtration resistance measurement revealed that
      RcsF(+) caused severe irreversible membrane fouling (i.e., pore-clogging),
      whereas less extracellular polysaccharide-producing strains caused moderate but
      reversible fouling to all membranes used in this study. Further cross-flow
      filtration tests indicated that colanic acid liberated in the bulk phase could
      rapidly penetrate pre-accumulated biomass layers (i.e., biofilms) and then
      directly clogged membrane pores. These results indicate that colanic acid, a
      hydrophilic extracellular polysaccharide, and possible polysaccharides with
      similar characteristics with colanic acid are considered as a major cause of
      severe irreversible membrane fouling (i.e., pore-clogging) regardless of biofilm
      formation (dynamic membrane). 

PMID- 25776919
TI  - Optimal clearance of Sporothrix schenckii requires an intact Th17 response in a
      mouse model of systemic infection.
AB  - The discovery of Th17 cells, along with many other Th cell subsets in the recent
      years, has expanded the Th1/Th2 paradigm that had persisted since its proposition
      by Mosmann in 1986. Defined by the characteristic expression of the transcription
      factor retinoic-related orphan receptor gammat (RORgammat) and production of IL
      17A (IL-17), Th17 cells are powerful inducers of tissue inflammation with a
      recognized role against extracellular bacteria and fungi. Despite this, the
      interest in their study came from the pivotal role they play in the development
      and maintenance of major chronic inflammatory conditions such as multiple
      sclerosis, rheumatoid arthritis and Crohn's disease, hence they have been the
      target of promising new anti-Th17 therapies. Accordingly, the identification of
      opportunistic pathogens whose clearance relies on the Th17 response is of huge
      prophylactic importance. As shown here for the first time, this applies to
      Sporothrix schenckii, a thermo-dimorphic fungus and the causative agent of
      sporotrichosis. Our results show that both Th17 and Th1/Th17 mixed cells are
      developed during the S. schenckii systemic mice infection, which also leads to
      augmented production of IL-17 and IL-22. Also, by using an antibody-mediated IL
      23 depletion model, we further demonstrate that optimal fungal clearance, but not
      survival, depends on an intact Th17 response. 

PMID- 25776920
TI  - Five winters of pneumococcal serotype replacement in UK carriage following PCV
      introduction.
AB  - The seven-valent pneumococcal conjugate vaccine (PCV7) was added to the UK
      national immunisation programme in September 2006. PCV13 replaced PCV7 in April
      2010. As carriage precedes disease cases this study collected carried pneumococci
      from children each winter from 2006/7 to 2010/11 over PCV introduction.
      Conventional microbiology and whole genome sequencing were utilised to
      characterise pneumococcal strains. Overall prevalence of pneumococcal carriage
      remained stable. Vaccine serotypes (VT) decreased (p<0.0001) with concomitant
      increases in non-vaccine serotypes (NVT). In winter 2010/11 only one isolate of
      PCV7 VT was observed (6B). PCV13 unique VTs decreased between winters immediately
      preceding and following PCV13 introduction (p=0.04). Significant decreases for
      VTs 6B, 19F, 23F (PCV7) and 6A (PCV13) and increases for NVT 21, 23B, 33F and 35F
      were detected. The serotype replacement was accompanied by parallel changes in
      genotype prevalence for associated sequence types with clonal expansion
      contributing to replacement. By winter 2010/11, serotype coverage of PCV7 and
      PCV13 was 1% and 11% respectively. VT replacement was observed for PCV7 and PCV13
      serotypes. Conjugate vaccine design and use requires continuous monitoring and
      revision. 

PMID- 25776921
TI  - Salmonella outer membrane vesicles displaying high densities of pneumococcal
      antigen at the surface offer protection against colonization.
AB  - Bacterial outer membrane vesicles (OMVs) are attractive vaccine formulations
      because they have intrinsic immunostimulatory properties. In principle,
      heterologous antigens incorporated into OMVs will elicit specific immune
      responses, especially if presented at the vesicle surface and thus optimally
      exposed to the immune system. In this study, we explored the feasibility of our
      recently developed autotransporter Hbp platform, designed to efficiently and
      simultaneously display multiple antigens at the surface of bacterial OMVs, for
      vaccine development. Using two Streptococcus pneumoniae proteins as model
      antigens, we showed that intranasally administered Salmonella OMVs displaying
      high levels of antigens at the surface induced strong protection in a murine
      model of pneumococcal colonization, without the need for a mucosal adjuvant.
      Importantly, reduction in bacterial recovery from the nasal cavity was correlated
      with local production of antigen-specific IL-17A. Furthermore, the protective
      efficacy and the production of antigen-specific IL-17A, and local and systemic
      IgGs, were all improved at increased concentrations of the displayed antigen.
      This discovery highlights the importance of an adequate antigen expression system
      for development of recombinant OMV vaccines. In conclusion, our findings
      demonstrate the suitability of the Hbp platform for development of a new
      generation of OMV vaccines, and illustrate the potential of using this approach
      to develop a broadly protective mucosal pneumococcal vaccine. 

PMID- 25776922
TI  - Implementation of pertussis immunization in health-care personnel.
AB  - BACKGROUND AND AIM: Infection with Bordetella pertussis is most severe in young
      infants who frequently acquire it from adults. Pertussis immunization in adults
      25-29 years of age and all adults in close contact with infants <6 months was
      introduced in Switzerland in 2012. We immediately implemented this new
      recommendation in our hospital with a vaccination campaign. METHODS: Between
      April 2012 and March 2013 we provided information about the campaign to our staff
      through several channels and offered appointments for counseling and
      immunization. After checking indications and contraindications of responding
      health-care personnel (HCP), informed consent for tetanus-diphtheria-acellular
      pertussis component (Tdap) immunization was obtained. Specific adverse events
      (AE) were self-assessed by standardized diaries for 7 days. Statistical analyses
      were performed using a t-test and Mann-Whitney U-tests SPSS (V21). RESULTS: Of
      852 HCP eligible for pertussis immunization, 427 (51%) responded. Of these, 72
      (17%) had already received Tdap <10 years ago, 304 (71%) received Tdap now, 38
      (9%) were scheduled for vaccination and 12 (3%) declined. Diaries were returned
      by 272 (89%) of 304 vaccinees; 56 HCP reported >=1 local AE, most frequently
      local swelling (8%), redness (2%), redness and swelling (7%), and fever (5=2%);
      no serious AE occurred. CONCLUSIONS: Comprehensive efforts were needed to achieve
      pertussis immunization coverage of >=49% among all HCP in our institution. Good
      tolerability of the vaccine and continuous and individual information to HCP
      about the rationale and benefits of pertussis immunization contributed to this
      partial success, but increased efforts are needed to mobilize non-responding HCP.

PMID- 25776923
TI  - The HPV16 E6 oncoprotein and UVB irradiation inhibit the tumor suppressor TGFbeta
      pathway in the epidermis of the K14E6 transgenic mouse.
AB  - High-risk human papillomaviruses (HR-HPVs) are the causative agents of cervical
      cancer, and they are also associated with a subset of head and neck squamous cell
      carcinomas. In addition, HPVs have also been postulated in the development of non
      melanoma skin cancers (NMSC). In these cancers, the oncogene E6 is best known for
      its ability to inactivate the tumor suppressor p53 protein. Interestingly, in
      transgenic mice for HPV16 E6 (K14E6), it was reported that E6 alone induced
      epithelial hyperplasia and delay in differentiation in skin epidermis
      independently of p53 inactivation. Transforming growth factor beta (TGFbeta) is
      an important regulator of cell growth/differentiation and apoptosis, and this
      pathway is often lost during tumorigenesis. Ultraviolet radiation B (UVB)
      exposure activates diverse cellular responses, including DNA damage and
      apoptosis. In this study, we investigated whether the E6 oncogene alone or in
      combination with UVB dysregulate some components of the TGFbeta pathway in the
      epidermis of K14E6 mice. We used 8-day-old K14E6 and non-transgenic mice
      irradiated and unirradiated with a single dose of UVB. We found that the E6
      oncogene and UVB irradiation impair the TGFbeta pathway in epidermis of K14E6
      mice by downregulation of the TGFbeta type II receptor (TbetaRII). This loss of
      TbetaRII prevents downstream activation of Smad2 and target genes as p15, an
      important regulator of cell cycle progression. In summary, the TGFbeta signalling
      in cells of the epidermis is downregulated in our mouse model by both the E6
      oncoprotein and the UVB irradiation. 

PMID- 25776925
TI  - Regulatory Framework for Clinical Decision Support Software: Present Uncertainty
      and Prospective Proposition.
AB  - US regulators have been slow to provide meaningful guidance to industry
      participants on the issue of clinical decision support (CDS) software. It is
      crucial that regulators soon clarify the differences between regulated medical
      devices and unregulated health management software that nevertheless has the
      potential to affect patient care. Future CDS regulation in the United States
      should aim to reduce ambiguity by establishing detailed and simple criteria for
      manufacturers to use in deciding if a CDS product will be regulated. Clear
      standards will help ensure the safety of CDS that is brought to market. In
      addition, clarification will facilitate technological innovation, delivering
      clinical benefits to needy patients. To this end, the regulatory framework
      implemented in the United States with respect to CDS should consider the
      "substantial dependence" standard. 

PMID- 25776924
TI  - Transcarotid aortic valve-in-valve implantation for degenerated stentless aortic
      root conduits with severe regurgitation: a case series.
AB  - OBJECTIVES: Transcatheter aortic valve implantation (TAVI) is routinely performed
      via the transfemoral and the transapical route. Subclavian and direct aortic
      access are described alternatives for TAVI. Recently, the transcarotid approach
      has been shown to be feasible among patients with limited vascular access and
      severe native aortic valve stenosis. We aim to investigate the feasibility of
      transcatheter aortic valve-in-valve implantation via the transcarotid access in
      patients with severe aortic regurgitation due to degenerated stentless Shelhigh
      conduits using the 29 mm Medtronic CoreValve bioprosthesis. METHODS: Three
      patients with complex vascular anatomy undergoing transcatheter valve-in-valve
      implantation via the transcarotid route were enrolled in the study. The procedure
      was performed under general anaesthesia using surgical cut-down to facilitate
      vascular access. Immediate procedural results as well as echocardiographic and
      clinical outcomes after 30 days and 6 months of the follow-up were recorded and
      analysed. RESULTS: All three patients underwent unproblematic TAVI and
      experienced dramatic improvement of symptoms. Mean transvalvular gradient was 3,
      6 and 11 mmHg, respectively. Effective orifice area ranged between 1.7 and 2.2
      cm(2). Only mild paravalvular regurgitation was detected by echocardiography
      after 30 days of the follow-up. CONCLUSIONS: The transcarotid approach can be
      safely performed for valve-in-valve procedures using the Medtronic CoreValve in
      patients with limited vascular access. It enables accurate positioning and
      implantation of the prosthesis.

PMID- 25776926
TI  - A method to select aperture margin in collimated spot scanning proton therapy.
AB  - The use of collimator or aperture may sharpen the lateral dose gradient for spot
      scanning proton therapy. However, to date, there has not been a standard method
      to determine the aperture margin for a single field in collimated spot scanning
      proton therapy. This study describes a theoretical framework to select the
      optimal aperture margin for a single field, and also presents the spot spacing
      limit required such that the optimal aperture margin exists. Since, for a proton
      pencil beam partially intercepted by collimator, the maximum point dose (spot
      center) shifts away from the original pencil beam central axis, we propose that
      the optimal margin should be equal to the maximum pencil beam center shift under
      the condition that spot spacing is small with respect to the maximum pencil beam
      center shift, which can be numerically determined based on beam modeling data. A
      test case is presented which demonstrates agreement with the prediction made
      based on the proposed methods. When apertures are applied in a commercial
      treatment planning system this method may be implemented. 

PMID- 25776927
TI  - Variable assessment of wing colouration in aerial contests of the red-winged
      damselfly Mnesarete pudica (Zygoptera, Calopterygidae).
AB  - Wing pigmentation is a trait that predicts the outcome of male contests in some
      damselflies. Thus, it is reasonable to suppose that males would have the ability
      to assess wing pigmentation and adjust investment in a fight according to the
      costs that the rival may potentially impose. Males of the damselfly Mnesarete
      pudica exhibit red-coloured wings and complex courtship behaviour and engage in
      striking male-male fights. In this study, we investigated male assessment
      behaviour during aerial contests. Theory suggests that the relationship between
      male resource-holding potential (RHP) and contest duration describes the kind of
      assessment adopted by males: self-assessment, opponent-only assessment or mutual
      assessment. A recent theory also suggests that weak and strong males exhibit
      variations in the assessment strategies adopted. We estimated male RHP through
      male body size and wing colouration (i.e. pigmentation, wing reflectance spectra
      and transmission spectra) and studied the relationship between male RHP and
      contest duration from video-documented behavioural observations of naturally
      occurring individual contests in the field. The results showed that males with
      more opaque wings and larger red spots were more likely to win contests. The
      relationships between RHP and contest durations partly supported the self
      assessment and the mutual assessment models. We then experimentally augmented the
      pigmented area of the wings, in order to evaluate whether strong and weak males
      assess rivals' RHP through wing pigmentation. Our experimental manipulation,
      however, clearly demonstrated that strong males assess rivals' wing pigmentation.
      We finally suggest that there is a variation in the assessment strategy adopted
      by males. 

PMID- 25776928
TI  - Rational design of a photo-crosslinking BODIPY for in situ protein labeling.
AB  - Photo-crosslinking agents have emerged as critical tools to investigate protein
      protein interactions in complex proteomes, but there are few photocrosslinkers
      available at the moment. Here, we report the first rational design of a photo
      crosslinking BODIPY fluorophore (pcBD) and its biological application for
      biomolecule labeling. As a photosensitizing functional motif, an aryl ketone
      group was incorporated into the BODIPY fluorophore, and a series of proteins were
      labeled by pcBD compounds upon UV irradiation. In order to investigate protein
      protein interactions in a protein mixture, amino-functionalized pcBD was prepared
      and covalently attached to a ubiquitin ligase binding peptide. Upon UV
      irradiation, we could successfully visualize the substrates in the total lysate.
      These results provided a proof of concept for spatially controllable tagging via
      photo-activation of the pcBD scaffold, and demonstrated its potential usage for
      in situ labeling applications.

PMID- 25776929
TI  - Variations in temperature acclimation effects on glycogen storage, hypoxia
      tolerance and swimming performance with seasonal acclimatization in juvenile
      Chinese crucian carp.
AB  - The aim of this study was to test whether temperature acclimation (10 vs 20 
      degrees C) effects on tissue glycogen content, hypoxia tolerance, and swimming
      performance of Chinese crucian carp (Carassius auratus) varied with seasonal
      acclimatization (winter vs spring) and potential combined interactions. Both the
      routine metabolic rate (MO(2rout)) and critical oxygen tension (P(crit)) of the
      MO(2rout) increased significantly with temperature, whereas the seasonal
      acclimatization showed no significant effect. Only the high temperature group
      that acclimatized in spring showed a significantly higher aquatic surface
      respiration (ASR(crit)) value compared with the other three groups. Fish in
      spring tended to show ASR behavior at higher oxygen tension compared with those
      in winter, which might have been caused by a more active lifestyle. Time to show
      LOE prolonged by 25-34% under low temperature. Spring fish showed 20% shorter LOE
      duration at 10  degrees C, whereas the difference tended to vanish at 20  degrees
      C. Glycogen contents in both liver and muscle were higher in winter than spring.
      The liver and muscle glycogen content decreased by 5-42% after exposure to anoxic
      conditions, whereas the magnitude was much smaller in spring. When fish swam in
      normoxic conditions, fish in higher temperatures showed higher critical swimming
      speed (Ucrit) than low temperature (5.49 vs 3.74 BL s(-1) in winter and 4.27 vs
      3.21 BL s(-1) in spring), whereas fish in winter also showed higher U(crit) than
      fish in spring for each temperature. However, when fish swam in hypoxic waters,
      fish in higher temperatures showed a more profound decrease (52-61%) in U(crit)
      compared to those in lower temperature (25-27%). Fish in lower temperatures that
      had acclimatized in winter showed the highest U(crit), which might have been
      caused by higher glycogen storage. The present study suggested that both glycogen
      storage and alterations in lifestyle had profound effects on hypoxia tolerance
      and swimming performance, which resulted in a profound difference between seasons
      and acclimation temperatures.

PMID- 25776930
TI  - Neural responses to others' pain vary with psychopathic traits in healthy adult
      males.
AB  - Disrupted empathic processing is a core feature of psychopathy. Neuroimaging data
      have suggested that individuals with high levels of psychopathic traits show
      atypical responses to others' pain in a network of brain regions typically
      recruited during empathic processing (anterior insula, inferior frontal gyrus,
      and mid- and anterior cingulate cortex). Here, we investigated whether neural
      responses to others' pain vary with psychopathic traits within the general
      population in a similar manner to that found in individuals at the extreme end of
      the continuum. As predicted, variation in psychopathic traits was associated with
      variation in neural responses to others' pain in the network of brain regions
      typically engaged during empathic processing. Consistent with previous research,
      our findings indicated the presence of suppressor effects in the association of
      levels of the affective-interpersonal and lifestyle-antisocial dimensions of
      psychopathy with neural responses to others' pain. That is, after controlling for
      the influence of the other dimension, higher affective-interpersonal psychopathic
      traits were associated with reduced neural responses to others' pain, whilst
      higher lifestyle-antisocial psychopathic traits were associated with increased
      neural responses to others' pain. Our findings provide further evidence that
      atypical function in this network might represent neural markers of disrupted
      emotional and empathic processing; that the two dimensions of psychopathy might
      tap into distinct underlying vulnerabilities; and, most importantly, that the
      relationships observed at the extreme end of the psychopathy spectrum apply to
      the nonclinical distribution of these traits, providing further evidence for
      continuities in the mechanisms underlying psychopathic traits across the general
      population. 

PMID- 25776931
TI  - The unseen child and safeguarding: 'Did not attend' guidelines in the NHS.
AB  - BACKGROUND: Organisations in England's National Health Service (NHS) are required
      to have 'did not attend' (DNA) guidelines to help deal with the 'unseen child'.
      AIMS: To map DNA and associated guidelines in paediatric services, examine
      differences in safeguarding response and advice in the guidelines and explore the
      experience of guideline users. METHODS: A mapping approach was used to locate
      current DNA guidelines on English NHS organisations' websites. Analysis of the
      guidelines was supplemented with qualitative data from those who produce, monitor
      or use them. RESULTS: Fewer than 8% of English NHS organisations had up-to-date
      guidelines in the public domain, though a further 41% stated that they had a
      DNA/similar policy in place or had an out-of-date guideline on their website.
      Advice to healthcare providers about the steps to take when a child DNAs fell
      into five categories: reflection and review; direct interaction with the family;
      indirect interaction with the family; liaison with internal colleagues; and
      external referral. Interviews with eight individuals led to the identification of
      four themes. The management of information flows was central to the effective
      management of DNA. Respondents also reported seeking support and advice from
      others. While all respondents spoke about the importance of supporting the
      family, the child's needs were central to dealing with non-attendance, and
      respondents demonstrated awareness of wider risk discourses. CONCLUSIONS: We
      consider the implications of the work and suggest that evidence-informed
      guidelines developed nationally but tailored to specific services might be
      helpful for providers and users alike.

PMID- 25776932
TI  - The role of the ionic liquid C6C1ImTFSI in the sol-gel synthesis of silica
      studied using in situ SAXS and Raman spectroscopy.
AB  - The sol-gel synthesis of a silica based ionogel using the ionic liquid 1-hexyl-3
      methylimidazolium bis(trifluoromethanesulfonyl)imide (C6C1ImTFSI) as the solvent
      has been followed in situ by combined MU-focused X-ray scattering and MU-Raman
      spectroscopy. By covering the momentum transfer range 0.2 < q < 30 nm(-1) we
      probe the evolution of the characteristic peaks of the ionic liquid, associated
      with the existence of polar and non-polar domains, as a function of reaction
      time. Our detailed analysis of the small angle X-ray scattered (SAXS) pattern
      reveals that the nano-structure of the ionic liquid is partially retained during
      the sol-gel synthesis, as indicated by the broader yet distinguishable SAXS
      signatures. We also observe that the signature associated with the non-polar and
      polar domains shift to higher and lower q-values, respectively. Interestingly,
      this behavior correlates with the evolution of the chemical composition of the
      sol as probed by Raman spectroscopy. More precisely, we observe that both the
      nano-structural changes and the production of polar molecules arrest at the point
      of gelation. This is rationalized by the tendency of the reagents and products of
      the sol-gel reaction to locate in different portions of the nano-structure of the
      ionic liquid. 

PMID- 25776933
TI  - Five-Year Cervical (Pre)Cancer Risk of Women Screened by HPV and Cytology
      Testing.
AB  - Primary human papillomavirus (HPV)-based cervical screening will be introduced in
      the Netherlands in 2016. We assessed the 5-year cervical (pre)cancer risk of
      women with different combinations of HPV and cytology test results. Special
      attention was paid to risks for cervical intraepithelial neoplasia grade 3 and 2
      or more (CIN3+/2+) of HPV-positive women with a negative triage test, because
      this determines the safety of a 5-year screening interval for HPV-positive,
      triage test-negative women. In addition, age-related effects were studied. A
      total of 25,553 women were screened by HPV testing and cytology in a screening
      setting. Women were managed on the presence of HPV and/or abnormal cytology. Five
      year cumulative incidences for CIN3+/2+ were calculated. Five-year CIN3+(2+) risk
      was 10.0% (17.7%) among HPV-positive women. When stratified by cytology, the
      CIN3+(CIN2+) risk was 7.9% (12.9%) for women with normal cytology and 22.2%
      (45.3%) for women with equivocal or mildly abnormal (i.e., BMD) cytology. For HPV
      negative women, the 5-year CIN3+(2+) risk was 0.09% (0.21%). Additional triage of
      HPV-positive women with normal cytology by repeat cytology at 12 months showed a
      5-year CIN3+(2+) risk of 4.1% (7.0%). HPV-non 16/18-positive women with normal
      cytology at baseline had comparable risks of 3.5% (7.9%). HPV-non 16/18-positive
      women with normal baseline cytology and normal repeat cytology had a 5-year CIN3+
      risk of 0.42%. No age-related effects were detected. In conclusion, HPV-positive
      women with normal cytology and a negative triage test, either repeat cytology
      after 12 months or baseline HPV 16/18 genotyping, develop a non-negligible CIN3+
      risk over 5 years. Therefore, extension of the screening interval over 5 years
      only seems possible for HPV screen-negative women.

PMID- 25776934
TI  - Caveolin-1 aggravates cigarette smoke extract-induced MUC5AC secretion in human
      airway epithelial cells.
AB  - Airway mucus hypersecretion is a major pathological characteristic of chronic
      obstructive pulmonary disease (COPD), and cigarette smoke is highly implicated in
      mucus secretion and the development of COPD. Cigarette smoke reportedly induces
      mucin overproduction through the epidermal growth factor receptor (EGFR) in the
      airway epithelium; however, the underlying mechanisms responsible for the
      activation of EGFR remain unknown. Caveolin-1, a component protein in the
      cytomembrane, reportedly regulates airway inflammation and lung injury. In this
      study, we aimed to determine whether caveolin-1 modulates mucin hyperproduction
      induced by cigarette smoke. Our results revealed that cigarette smoke extract
      (CSE) significantly increased MUC5AC production, as well as the levels of
      phosphorylated EGFR (p-EGFR) and phosphorylated Akt (p-Akt) in human bronchial
      epithelial cells (16HBE cells), as shown by ELISA, RT-PCR and western blot
      analysis. These effects were prevented by treatment with EGFR inhibitor (AG1478)
      and phosphatidylinostol-3-kinase (PI3K) inhibitor (LY294002). We also found that
      the overexpression of caveolin-1 enhanced the expression of MUC5AC, p-EGFR and p
      Akt induced by CSE. Conversely, the downregulation of caveolin-1 by siRNA against
      caveolin-1 inhibited the expression of MUC5AC, p-EGFR and p-Akt. Taken together,
      our data suggest that caveolin-1 enhances CSE-induced MUC5AC hypersecretion
      through the EGFR/PI3K/Akt signaling pathway.

PMID- 25776935
TI  - Recent trends in euthanasia and other end-of-life practices in Belgium.

PMID- 25776936
TI  - Systemic inflammatory response syndrome criteria in defining severe sepsis.
AB  - BACKGROUND: The consensus definition of severe sepsis requires suspected or
      proven infection, organ failure, and signs that meet two or more criteria for the
      systemic inflammatory response syndrome (SIRS). We aimed to test the sensitivity,
      face validity, and construct validity of this approach. METHODS: We studied data
      from patients from 172 intensive care units in Australia and New Zealand from
      2000 through 2013. We identified patients with infection and organ failure and
      categorized them according to whether they had signs meeting two or more SIRS
      criteria (SIRS-positive severe sepsis) or less than two SIRS criteria (SIRS
      negative severe sepsis). We compared their characteristics and outcomes and
      assessed them for the presence of a step increase in the risk of death at a
      threshold of two SIRS criteria. RESULTS: Of 1,171,797 patients, a total of
      109,663 had infection and organ failure. Among these, 96,385 patients (87.9%) had
      SIRS-positive severe sepsis and 13,278 (12.1%) had SIRS-negative severe sepsis.
      Over a period of 14 years, these groups had similar characteristics and changes
      in mortality (SIRS-positive group: from 36.1% [829 of 2296 patients] to 18.3%
      [2037 of 11,119], P<0.001; SIRS-negative group: from 27.7% [100 of 361] to 9.3%
      [122 of 1315], P<0.001). Moreover, this pattern remained similar after adjustment
      for baseline characteristics (odds ratio in the SIRS-positive group, 0.96; 95%
      confidence interval [CI], 0.96 to 0.97; odds ratio in the SIRS-negative group,
      0.96; 95% CI, 0.94 to 0.98; P=0.12 for between-group difference). In the adjusted
      analysis, mortality increased linearly with each additional SIRS criterion (odds
      ratio for each additional criterion, 1.13; 95% CI, 1.11 to 1.15; P<0.001) without
      any transitional increase in risk at a threshold of two SIRS criteria.
      CONCLUSIONS: The need for two or more SIRS criteria to define severe sepsis
      excluded one in eight otherwise similar patients with infection, organ failure,
      and substantial mortality and failed to define a transition point in the risk of
      death. (Funded by the Australian and New Zealand Intensive Care Research
      Centre.).

PMID- 25776937
TI  - MicroRNA-423-5p targets O-GlcNAc transferase to induce apoptosis in
      cardiomyocytes.
AB  - Congestive heart failure (CHF) remains the single most prevalent cause of
      mortality and morbidity; therefore, the identification of novel biomarkers is
      required for the diagnosis of CHF. The aim of the present study was to examine
      whether microRNA (miR)-423-5p is a novel biomarker for CHF, which was defined by
      the circulatory biomarker pro-brain natriuretic peptide (BNP). Samples of plasma
      from patients with CHF and healthy controls were collected and used for
      quantitative polymerase chain reaction analysis. In addition, the O-GlcNAc
      transferase (OGT) 3' untranslated region was cloned and used for a luciferase
      assay. The effects of the expression of miR-423-5p in cardiomyocytes were
      determined using western blotting and terminal deoxynucleotidyl transferase
      deoxyuridine triphosphate nick-end labeling analyses. The results demonstrated
      that miR-423-5p was associated with CHF and the expression levels of proBNP; in
      addition, OGT was found to be a direct target of miR-423-5p. The expression of
      miR-423-5p significantly regulated the expression of OGT and its associated
      downstream targets and induced apoptosis in the cardiomyocytes. Therefore, the
      results of the present study indicated that miR-423-5p was involved in CHF via
      the direct targeting of OGT and the induction of apoptosis in cardiomyocytes.

PMID- 25776938
TI  - Explant cultures of atopic dermatitis biopsies maintain their epidermal
      characteristics in vitro.
AB  - Atopic dermatitis (AD) is a common inflammatory skin disorder characterised by
      various epidermal alterations. Filaggrin (FLG) mutations are a major predisposing
      factor for AD and much research has been focused on the FLG protein. Human skin
      equivalents (HSEs) might be useful tools for increasing our understanding of FLG
      in AD and to provide a tool for the screening of new therapies aimed at FLG
      replacement. Our aim is to establish an explant HSE (Ex-HSE) for AD by using non
      lesional skin from AD patients wildtype for FLG or harbouring homozygous FLG
      mutations. These Ex-HSEs were evaluated as to whether they maintained their in
      vivo characteristics in vitro and whether FLG mutations affected the expression
      of various differentiation markers. FLG mutations did not affect the outgrowth
      from the biopsy for the establishment of Ex-HSEs. FLG expression was present in
      healthy skin and that of AD patients without FLG mutations and in their Ex-HSEs
      but was barely present in biopsies from patients with FLG mutations and their
      corresponding Ex-HSEs. AD Ex-HSEs and AD biopsies shared many similarities, i.e.,
      proliferation and the expression of keratin 10 and loricrin, irrespective of FLG
      mutations. Neither KLK5 nor Lekti expression was affected by FLG mutations but
      was altered in the respective Ex-HSEs. Thus, Ex-HSEs established from biopsies
      taken from AD patients maintain their FLG genotype-phenotype in vitro and the
      expression of most proteins in vivo and in vitro remains similar. Our method is
      therefore promising as an alternative to genetic engineering approaches in the
      study of the role of FLG in AD. 

PMID- 25776939
TI  - Bracketing subtle conformational energy differences between self-solvated and
      stretched trifluoropropanol.
AB  - The intramolecular OH...F hydrogen bond in 3,3,3-trifluoropropanol (TFP) exerts a
      subtle stabilizing effect that, when compared to the non-fluorinated analog,
      reorders the five distinguishable conformers and widens the gap between the two
      most stable structures. Here, we combine findings from Raman spectroscopy in
      supersonic expansions and high-level quantum-chemical calculations to bracket the
      energy difference between the two most stable TFP structures at 1.7(5) kJ mol(
      1). The torsional potential energy surface suggests consecutive backbone and OH
      torsional motions for the conformer interconversion, which are discussed in the
      framework of supersonic jet cooling as a function of nozzle temperature. The
      picture of a bistable cold molecule with trans or gauche backbone emerges, in
      which the OH group controls the energy difference and modulates the high barrier
      separating the heavy atom frames.

PMID- 25776940
TI  - 'Annexins' themed section.

PMID- 25776941
TI  - Choice of flap affects fistula rate after salvage laryngopharyngectomy.
AB  - Due to the significant morbidity and mortality associated with pharyngocutaneous
      fistula in pharyngoesophageal reconstruction following cancer resection, the
      purpose of this retrospective study is to examine the selection of tubed skin
      flaps that impact anastomotic integrity. The flaps evaluated included radial
      forearm flap versus anterolateral thigh flap, and fasciocutaneous anterolateral
      thigh flap versus chimeric anterolateral thigh flap. The outcome of interest is
      the incidence of pharyngocutaneous fistula. The radial forearm group had a
      significantly higher rate of fistula than the anterolateral thigh group (56.6%
      vs. 30.2%, p = 0.03). No significant difference in the incidence of fistula was
      demonstrated between fasciocutaneous and chimeric anterolateral thigh flap (36.8%
      vs. 25%, p = 0.51). The anastomotic integrity in pharyngoesopharyngeal
      reconstruction is affected by choice of skin flaps. Anterolateral thigh flap
      appears to be a viable option for pharyngoesophageal reconstruction. The more
      technical demand of the anterolateral thigh flap must be weighed against an
      easily harvested radial forearm flap. 

PMID- 25776942
TI  - Dietary management of labrador retrievers with subclinical hepatic copper
      accumulation.
AB  - BACKGROUND: Genetic and environmental factors, including dietary copper intake,
      contribute to the pathogenesis of copper-associated hepatitis in Labrador
      retrievers. Clinical disease is preceded by a subclinical phase in which copper
      accumulates in the liver. OBJECTIVE: To investigate the effect of a low-copper,
      high-zinc diet on hepatic copper concentration in Labrador retrievers with
      increased hepatic copper concentrations. ANIMALS: Twenty-eight clinically
      healthy, client-owned Labrador retrievers with a mean hepatic copper
      concentration of 919 +/- 477 mg/kg dry weight liver (dwl) that were related to
      dogs previously diagnosed with clinical copper-associated hepatitis. METHODS:
      Clinical trial in which dogs were fed a diet containing 1.3 +/- 0.3 mg
      copper/Mcal and 64.3 +/- 5.9 mg zinc/Mcal. Hepatic copper concentrations were
      determined in liver biopsy samples approximately every 6 months. Logistic
      regression was performed to investigate effects of sex, age, initial hepatic
      copper concentration and pedigree on the ability to normalize hepatic copper
      concentrations. RESULTS: In responders (15/28 dogs), hepatic copper
      concentrations decreased from a mean of 710 +/- 216 mg/kg dwl copper to 343 +/-
      70 mg/kg dwl hepatic copper after a median of 7.1 months (range, 5.5-21.4
      months). Dogs from a severely affected pedigree were at increased risk for
      inability to have their hepatic copper concentrations normalized with dietary
      treatment. CONCLUSIONS AND CLINICAL IMPORTANCE: Feeding a low-copper, high-zinc
      diet resulted in a decrease in hepatic copper concentrations in a subset of
      clinically normal Labrador retrievers with previous hepatic copper accumulation.
      A positive response to diet may be influenced by genetic background.
      Determination of clinical benefit requires further study.

PMID- 25776943
TI  - Serum betatrophin concentrations are significantly increased in overweight but
      not in obese or type 2 diabetic individuals.
AB  - OBJECTIVE: In this study, circulating serum betatrophin levels were quantitated
      and their relationships with insulin resistance (IR) and other metabolic
      parameters in Chinese subjects with varying degrees of obesity and glucose
      tolerance were examined. METHODS: Serum betatrophin levels were determined using
      ELISA in 60 subjects with normal glucose tolerance (NGT: 17 lean, 23 overweight,
      and 20 obese subjects) and 56 subjects with type 2 diabetes mellitus (T2DM: 14
      lean, 23 overweight, and 19 obese subjects). The associations of serum
      betatrophin levels with adiposity, glucose, lipid profile, and hepatic enzyme
      parameters were studied. RESULTS: Serum betatrophin concentrations were
      significantly higher in overweight subjects in both the NGT and T2DM groups;
      however, no significant difference between lean and obese participants was
      observed. No significant difference was found between males and females or
      between NGT and T2DM subjects. Serum betatrophin concentrations correlated
      positively with fasting insulin, homeostasis model assessment-estimated insulin
      resistance (HOMA-IR), gamma-glutamyl transpeptidase (gamma-GT), and alanine
      aminotransferase (ALT) in all subjects. Serum betatrophin concentrations showed
      an independent association with gamma-GT and HOMA-IR. CONCLUSIONS: Serum
      betatrophin levels were significantly increased in overweight individuals but not
      in individuals with obesity or T2DM. Serum betatrophin concentrations were
      significantly associated with IR, but not with lipid profiles, glucose
      homeostasis, or diabetes.

PMID- 25776944
TI  - Inorganic polyphosphate elicits pro-inflammatory responses through activation of
      the mammalian target of rapamycin complexes 1 and 2 in vascular endothelial
      cells.
AB  - BACKGROUND: Inorganic polyphosphate (polyP) elicits pro-inflammatory signaling
      responses in endothelial cells through interaction with two receptors, RAGE and
      P2Y1 . It is known that polyP activates mTOR signaling in breast cancer cells.
      OBJECTIVES: The objective of this study is to understand the mechanism of the
      polyP-mediated signaling pathway in endothelial cells and to determine whether
      polyP exerts its pro-inflammatory effect through activation of mTOR. METHODS:
      mTOR activation by polyP or platelet releasates in cellular and animal models was
      monitored in the absence and presence of pharmacological inhibitors and/or siRNA
      knockdown of specific signaling molecules. RESULTS: PolyP effectively induced
      phosphorylation of mTOR complex 1 (mTORC1) substrate, p70S6K, in endothelial
      cells by an AKT-dependent but ERK-independent mechanism. The siRNA knockdown of
      both RAGE and P2Y1 or specific inhibitors of the PI3K/PLC/PKC/Ca(2+) signaling
      axis inhibited polyP-mediated p70S6K phosphorylation. Moreover, either rapamycin
      or siRNA knockdown of raptor (mTORC1-specific component) abrogated polyP-mediated
      phosphorylation of p70S6K. By contrast, the siRNA knockdown of rictor (mTOR
      complex 2-specific component) but not raptor eliminated the barrier-disruptive
      effect of polyP. Specific NF-kappaB inhibitors abrogated polyP-mediated
      phosphorylation of p70S6K and rapamycin suppressed polyP-induced activation of NF
      kappaB. Finally, specific inhibitors of the mTOR signaling network eliminated
      polyP-mediated vascular leakage and leukocyte recruitment in animal models.
      CONCLUSIONS: PolyP, through interaction with RAGE and P2Y1 , activates both the
      mTORC1 and mTORC2 signaling network. Both the pro-inflammatory and mTOR signaling
      functions of polyP are linked.

PMID- 25776945
TI  - Glycopeptide mimetics recapitulate high-mannose-type oligosaccharide binding and
      function.
AB  - High-mannose-type glycans (HMTGs) decorating viral spike proteins are targets for
      virus neutralization. For carbohydrate-binding proteins, multivalency is
      important for high avidity binding and potent inhibition. To define the chemical
      determinants controlling multivalent interactions we designed glycopeptide HMTG
      mimetics with systematically varied mannose valency and spacing. Using the potent
      antiviral lectin griffithsin (GRFT) as a model, we identified by NMR
      spectroscopy, SPR, analytical ultracentrifugation, and microcalorimetry
      glycopeptides that fully recapitulate the specificity and kinetics of binding to
      Man9 GlcNAc2 Asn and a synthetic nonamannoside. We find that mannose spacing and
      valency dictate whether glycopeptides engage GRFT in a face-to-face or an
      intermolecular binding mode. Surprisingly, although face-to-face interactions are
      of higher affinity, intermolecular interactions are longer lived. These findings
      yield key insights into mechanisms involved in glycan-mediated viral inhibition. 

PMID- 25776946
TI  - Assistance of molecular vibrations on coherent energy transfer in photosynthesis
      from the view of a quantum heat engine.
AB  - Recently, the quantum nature in the energy transport in solar cells and light
      harvesting complexes has attracted much attention as being triggered by the
      experimental observations. We model the light-harvesting complex (i.e., PEB50
      dimer) as a quantum heat engine (QHE) and study the effect of the undamped
      intramolecule vibrational modes on the coherent energy-transfer process and
      quantum transport. We find that the exciton-vibration interaction has nontrivial
      contribution to the promotion of quantum yield as well as transport properties of
      the QHE at steady state by enhancing the quantum coherence quantified by
      entanglement entropy. The perfect quantum yield over 90% has been obtained, with
      the exciton-vibration coupling. We attribute these improvements to the
      renormalization of the electronic couplings effectively induced by exciton
      vibration interaction and the subsequent delocalization of excitons. Finally, we
      demonstrate that the thermal relaxation and dephasing can help the excitation
      energy transfer in the PEB50 dimer. 

PMID- 25776950
TI  - Autoimmunity: lungs and citrullination.
AB  - Anti-citrullinated protein antibodies are a distinctive feature of a subset of
      patients with rheumatoid arthritis (RA). A new report investigates how lung
      inflammation in patients with chronic obstructive pulmonary disease affects
      protein citrullination, providing an additional piece of information on the
      potential link between airway inflammation and RA.

PMID- 25776947
TI  - The current state of scaffolds for musculoskeletal regenerative applications.
AB  - Musculoskeletal disease and injury are highly prevalent conditions that lead to
      many surgical procedures. Autologous tissue transfer, allograft transplantation
      and nontissue prosthetics are currently used for the surgical treatment of
      critical-sized defects. However, the field of tissue engineering is actively
      investigating tissue-replacement solutions, many of which involve 3D scaffolds.
      Scaffolds must provide a balance of shape, biomechanical function and
      biocompatibility in order to achieve tissue replacement success. Different
      tissues can have different requirements for success, which has led to the
      development of various materials with unique characteristics. Articular cartilage
      scaffolds have the most robust clinical experience, with many scaffolds, mostly
      constructed of natural materials, showing promise, but levels of success vary.
      Tendon scaffolds also have proven clinical applications, with human-dermis
      derived scaffolds showing the most potential. Synthetic and naturally derived
      meniscus scaffolds have been investigated in few clinical studies, but the
      results are encouraging. Bone scaffolds are limited to amorphous pastes and
      putties, owing to difficulties achieving adequate vascularization and
      biomechanical optimization. The complex physiological function and vascular
      demands of skeletal muscle have limited the widespread clinical use of scaffolds
      for engineering this tissue. Continued progress in preclinical study, not only of
      scaffolds, but also of other facets of tissue engineering, should enable the
      successful translation of musculoskeletal tissue engineering solutions to the
      clinic. 

PMID- 25776949
TI  - Gene therapy approaches to regenerating the musculoskeletal system.
AB  - Injuries to the musculoskeletal system are common, debilitating and expensive. In
      many cases, healing is imperfect, which leads to chronic impairment. Gene
      transfer might improve repair and regeneration at sites of injury by enabling the
      local, sustained and potentially regulated expression of therapeutic gene
      products; such products include morphogens, growth factors and anti-inflammatory
      agents. Proteins produced endogenously as a result of gene transfer are nascent
      molecules that have undergone post-translational modification. In addition, gene
      transfer offers particular advantages for the delivery of products with an
      intracellular site of action, such as transcription factors and noncoding RNAs,
      and proteins that need to be inserted into a cell compartment, such as a
      membrane. Transgenes can be delivered by viral or nonviral vectors via in vivo or
      ex vivo protocols using progenitor or differentiated cells. The first gene
      transfer clinical trials for osteoarthritis and cartilage repair have already
      been completed. Various bone-healing protocols are at an advanced stage of
      development, including studies with large animals that could lead to human
      trials. Other applications in the repair and regeneration of skeletal muscle,
      intervertebral disc, meniscus, ligament and tendon are in preclinical
      development. In addition to scientific, medical and safety considerations,
      clinical translation is constrained by social, financial and logistical issues. 

PMID- 25776954
TI  - Education and imaging. Gastrointestinal: An abnormal MRI--remember the history.

PMID- 25776953
TI  - Outcomes of nonsevere relapses in antineutrophil cytoplasmic antibody-associated
      vasculitis treated with glucocorticoids.
AB  - OBJECTIVE: Nonsevere relapses are more common than severe relapses in
      antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), but their
      clinical course and treatment outcomes remain largely unexamined. We undertook
      this study to analyze the outcomes of patients with nonsevere relapses in the
      Rituximab in ANCA-Associated Vasculitis (RAVE) trial who were treated with
      prednisone according to a prespecified protocol. METHODS: RAVE was a randomized,
      double-blind, placebo-controlled trial comparing rituximab (RTX) to
      cyclophosphamide (CYC) followed by azathioprine (AZA) for induction of remission.
      Patients who experienced nonsevere relapses between months 1 and 18 were treated
      with a prednisone increase without a concomitant change in their
      nonglucocorticoid immunosuppressants, followed by a taper. RESULTS: Forty-four
      patients with a first nonsevere relapse were analyzed. In comparison to the 71
      patients who maintained relapse-free remission over 18 months, these patients
      were more likely to have proteinase 3-ANCAs, diagnoses of granulomatosis with
      polyangiitis (Wegener's), and a history of relapsing disease at baseline. A
      prednisone increase led to remission in 35 patients (80%). However, only 13
      patients (30%) were able to maintain second remissions through the followup
      period (mean 12.5 months); 31 patients (70%) had a second disease relapse, 14 of
      them with severe disease. The mean time to second relapse was 9.4 months (4.7
      months in the group treated with RTX versus 13.7 months in the group treated with
      CYC/AZA; P < 0.01). Patients who experienced nonsevere relapses received more
      glucocorticoids than those who maintained remission (6.7 grams versus 3.8 grams;
      P < 0.01). CONCLUSION: Treatment of nonsevere relapses in AAV with an increase in
      glucocorticoids is effective in restoring temporary remission in the majority of
      patients, but recurrent relapses within a relatively short interval remain
      common. Alternative treatment approaches are needed for this important subset of
      patients.

PMID- 25776955
TI  - Education and imaging. Gastrointestinal: Porcelain gallbladder.

PMID- 25776956
TI  - Education and imaging. Gastroenterology: Endoscopic ultrasonography (EUS) guided
      rendezvous bile duct metallic stenting in a patient with prior duodenal stent.

PMID- 25776957
TI  - Education and imaging. Gastroenterology: Small bowel intussusception from
      metastatic melanoma with retained video capsule.

PMID- 25776958
TI  - Education and imaging. Gastroenterology: Juxtapapillary diverticulum perforation
      after endoscopic retrograde cholangiopancreatography.

PMID- 25776959
TI  - Education and imaging. Gastrointestinal: An uncommon cause of gastrointestinal
      bleeding: spontaneous hematoma of the colon.

PMID- 25776960
TI  - Education and imaging. Gastroenterology: Diaphragmatic herniation and
      pancreatitis.

PMID- 25776961
TI  - Education and imaging. Gastrointestinal: Gastric involvement in disseminated
      lymphadenopathic Kaposi sarcoma.

PMID- 25776962
TI  - Education and imaging. Hepatobiliary and pancreatic: A splenic artery aneurysm
      presenting as a calcified pancreatic mass.

PMID- 25776963
TI  - Education and imaging. Hepatology: Rare Stevens-Johnson syndrome and vanishing
      bile duct syndrome induced by acetaminophen, requiring liver transplantation.

PMID- 25776965
TI  - Design and application of a novel in situ nano-manipulation stage for
      transmission electron microscopy.
AB  - A novel nano-scale manipulator capable of handling low-dimensional materials with
      three-dimensional linear motion, gripping action, and push-pull action of the
      gripper was developed for an in situ experiment in transmission electron
      microscopy. X-Y-Z positioning and push-pull action were accomplished by a
      piezotubing system, combined with a specially designed assembly stage that
      consisted of a lever-action gripping tip backed by a push-pull piezostack. The
      gripper tip consisted of tungsten wire fabricated by electrochemical etching
      followed by a focused ion beam process. Performance of the nano-scale manipulator
      was demonstrated in a grab-and-pick test of a single silver nanowire and in an in
      situ tensile test of a pearlitic steel sample with a specific orientation. 

PMID- 25776964
TI  - Use of a lipid-coated mesoporous silica nanoparticle platform for synergistic
      gemcitabine and paclitaxel delivery to human pancreatic cancer in mice.
AB  - Recently, a commercial albumin-bound paclitaxel (PTX) nanocarrier (Abraxane) was
      approved as the first new drug for pancreatic ductal adenocarcinoma in almost a
      decade. PTX improves the pharmaceutical efficacy of the first-line pancreatic
      cancer drug, gemcitabine (GEM), through suppression of the tumor stroma and
      inhibiting the expression of the GEM-inactivating enzyme, cytidine deaminase
      (CDA). We asked, therefore, whether it was possible to develop a mesoporous
      silica nanoparticle (MSNP) carrier for pancreatic cancer to co-deliver a
      synergistic GEM/PTX combination. High drug loading was achieved by a custom
      designed coated lipid film technique to encapsulate a calculated dose of GEM (40
      wt %) by using a supported lipid bilayer (LB). The uniform coating of the 65 nm
      nanoparticles by a lipid membrane allowed incorporation of a sublethal amount of
      hydrophobic PTX, which could be co-delivered with GEM in pancreatic cells and
      tumors. We demonstrate that ratiometric PTX incorporation and delivery by our LB
      MSNP could suppress CDA expression, contemporaneous with induction of oxidative
      stress as the operating principle for PTX synergy. To demonstrate the in vivo
      efficacy, mice carrying subcutaneous PANC-1 xenografts received intravenous (IV)
      injection of PTX/GEM-loaded LB-MSNP. Drug co-delivery provided more effective
      tumor shrinkage than GEM-loaded LB-MSNP, free GEM, or free GEM plus Abraxane.
      Comparable tumor shrinkage required coadministration of 12 times the amount of
      free Abraxane. High-performance liquid chromatography analysis of tumor
      associated GEM metabolites confirmed that, compared to free GEM, MSNP co-delivery
      increased the phosphorylated DNA-interactive GEM metabolite 13-fold and decreased
      the inactivated and deaminated metabolite 4-fold. IV injection of MSNP-delivered
      PTX/GEM in a PANC-1 orthotopic model effectively inhibited primary tumor growth
      and eliminated metastatic foci. The enhanced in vivo efficacy of the dual
      delivery carrier could be achieved with no evidence of local or systemic
      toxicity. In summary, we demonstrate the development of an effective LB-MSNP
      nanocarrier for synergistic PTX/GEM delivery in pancreatic cancer. 

PMID- 25776966
TI  - Human cytomegalovirus induced pseudotumor of upper gastrointestinal tract mucosa:
      effects of long-term chronic disease?
AB  - Human cytomegalovirus-induced lesions resembling malignancies have been described
      in the gastrointestinal tract and include ulcerated or exophytic large masses.
      The aim of this study was to review the cases registered in the databases of two
      academic hospitals and formulate a hypothesis concerning the pathogenic
      mechanisms responsible for cytomegalovirus-induced pseudotumor development. All
      the diagnoses of human cytomegalovirus infections of the upper gastrointestinal
      tract recorded from 1991 to 2013 were reviewed. Cases of mucosal alterations
      misdiagnosed endoscopically as malignancies were selected. Large ulcers occurring
      in the stomach (three cases) and an irregular exophytic mass at the gastro
      jejunal anastomosis were misdiagnosed endoscopically as malignancies (4 cases out
      of 53). Histologically, all lesions reflected hyperplastic mucosal changes with a
      prevalence of epithelial and stroma infected cells, without signs of cell atypia.
      The hypothesis presented is that the development of human cytomegalovirus-induced
      pseudotumors may be the morphological expression of chronic mucosa damage
      underlying long-term infection.

PMID- 25776984
TI  - Design and Evaluation of the Highly Concentrated Human IgG Formulation Using
      Cyclodextrin Polypseudorotaxane Hydrogels.
AB  - To achieve the potent therapeutic effects of human immunoglobulin G (IgG), highly
      concentrated formulations are required. However, the stabilization for highly
      concentrated human IgG is laborious work. In the present study, to investigate
      the potentials of polypseudorotaxane (PPRX) hydrogels consisting of polyethylene
      glycol (PEG) and alpha- or gamma-cyclodextrin (alpha- or gamma-CyD) as
      pharmaceutical materials for highly concentrated human IgG, we designed the PPRX
      hydrogels including human IgG and evaluated their pharmaceutical properties. The
      alpha- and gamma-CyDs formed PPRX hydrogels with PEG (M.W. 20,000) even in the
      presence of highly concentrated human IgG (>100 mg/mL). According to the results
      of (1)H-NMR, powder X-ray diffraction, and Raman microscopy, the formation of
      human IgG/CyD PPRX hydrogels was based on physical cross-linking arising from
      their columnar structures. The release profiles of human IgG from the hydrogels
      were in accordance with the non-Fickian diffusion model. Importantly, the
      stabilities of human IgG included into the hydrogels against thermal and shaking
      stresses were markedly improved. These findings suggest that PEG/CyD PPRX
      hydrogels are useful to prepare the formulation for highly concentrated human
      IgG.

PMID- 25776985
TI  - Heat-Stable Dry Powder Oxytocin Formulations for Delivery by Oral Inhalation.
AB  - In this work, heat stable dry powders of oxytocin (OT) suitable for delivery by
      oral inhalation were prepared. The OT dry powders were prepared by spray drying
      using excipients chosen to promote OT stability including trehalose, isoleucine,
      polyvinylpyrrolidone, citrate (sodium citrate and citric acid), and zinc salts
      (zinc chloride and zinc citrate). Characterization by laser diffraction indicated
      that the OT dry powders had a median particle size of 2 MUm, making them suitable
      for delivery by inhalation. Aerodynamic performance upon discharge from
      proprietary dry powder inhalers was evaluated by Andersen cascade impaction (ACI)
      and in an anatomically correct airway (ACA) model, and confirmed that the powders
      had excellent aerodynamic performance, with respirable fractions up to 77% (ACI,
      30 L/min). Physicochemical characterization demonstrated that the powders were
      amorphous (X-ray diffraction) with high glass transition temperature (modulated
      differential scanning calorimetry, MDSC), suggesting the potential for
      stabilization of the OT in a glassy amorphous matrix. OT assay and impurity
      profile were conducted by reverse phase HPLC and liquid chromatography-mass
      spectrometry (LC-MS) after storage up to 32 weeks at 40 degrees C/75%RH. Analysis
      demonstrated that OT dry powders containing a mixture of citrate and zinc salts
      retained more than 90% of initial assay after 32 weeks storage and showed
      significant reduction in dimers and trisulfide formation (up to threefold
      reduction compared to control).

PMID- 25776986
TI  - Progress in implantable cardioverter-defibrillator therapy: Advancement beyond
      technology alone.

PMID- 25776987
TI  - Mast cell-MrgprB2: sensing secretagogues or a means to overreact?

PMID- 25776988
TI  - The epigenetic mechanisms that underlie health and disease.

PMID- 25776989
TI  - Epigenomics of autoimmune diseases.
AB  - Autoimmune diseases are complex disorders of largely unknown etiology. Genetic
      studies have identified a limited number of causal genes from a marginal number
      of individuals, and demonstrated a high degree of discordance in monozygotic
      twins. Studies have begun to reveal epigenetic contributions to these diseases,
      primarily through the study of DNA methylation, but chromatin and non-coding RNA
      changes are also emerging. Moving forward an integrative analysis of genomic,
      transcriptomic and epigenomic data, with the latter two coming from specific cell
      types, will provide an understanding that has been missed from genetics alone. We
      provide an overview of the current state of the field and vision for deriving the
      epigenomics of autoimmunity. 

PMID- 25776990
TI  - Long noncoding RNAs: a potent source of regulation in immunity and disease.
AB  - The discovery of functional long noncoding RNAs (lncRNAs) coupled with the ever
      increasing accessibility of genomic and transcriptomic technology has led to an
      explosion of functional and mechanistic investigation and discovery into what was
      once dismissed as junk DNA. Over the past decade, a significant number of lncRNAs
      have been found to be involved in a diverse array of processes: from epigenetic
      modulation, both repressive and activating; to protein scaffolding; to miRNA
      sequestration; to competitive inhibition; and more. The broad character of these
      mechanisms means that lncRNAs have the potential for regulation across all
      biological processes-not least of which are immunity and disease. A number of
      lncRNAs operating within these two contexts have already been identified and
      characterized, but untold more remain yet to be discovered. This review aims to
      provide an overview of the current state of research on lncRNAs involved in
      immune modulation and disease, with an emphasis on their mechanism and discovery.

PMID- 25776991
TI  - CORRIGENDUM: Landscape cultivation alters delta30Si signature in terrestrial
      ecosystems.

PMID- 25776992
TI  - Association of human papillomavirus with Fanconi anemia promotes carcinogenesis
      in Fanconi anemia patients.
AB  - Fanconi anemia (FA) is a rare recessive disorder associated with chromosomal
      fragility. FA patients are at very high risk of cancers, especially head and neck
      squamous cell carcinomas and squamous cell carcinomas caused by infection of
      human papillomaviruses (HPVs). By integrating into the host genome, HPV oncogenes
      E6 and E7 drive the genomic instability to promote DNA damage and gene mutations
      necessary for carcinogenesis in FA patients. Furthermore, E6 and E7 oncoproteins
      not only inhibit p53 and retinoblastoma but also impair the FANC/BRCA signaling
      pathway to prevent DNA damage repair and alter multiple signals including cell
      cycle checkpoints, telomere function, cell proliferation, and interference of the
      host immune system leading to cancer development in FA patients. In this review,
      we summarize recent advances in unraveling the molecular mechanisms of FA
      susceptibility to HPV-induced cancers, which facilitate rational preventive and
      therapeutic strategies.

PMID- 25776993
TI  - Dienogest. A possible conservative approach in bladder endometriosis. Results of
      a pilot study.
AB  - Deep endometriosis involvement of the bladder is uncommon but it is symptomatic
      in most of the cases. Although laparoscopic excision is very effective, some
      patients with no pregnancy desire require a medical approach. We performed a
      pilot study on the effect of a new progestin dienogest on bladder endometriosis.
      Six patients were treated for 12 months with dienogest 2 mg/daily. Pain, urinary
      symptoms, quality of life, nodule volume and side effects were recorded. During
      treatment, symptoms improved very quickly and the nodules exhibit a remarkable
      reduction in size. Dienogest may be an alternative approach to bladder
      endometriosis. 

PMID- 25776994
TI  - Major decline in marine and terrestrial animal consumption by brown bears (Ursus
      arctos).
AB  - Human activities have had the strongest impacts on natural ecosystems since the
      last glacial period, including the alteration of interspecific relationships such
      as food webs. In this paper, we present a historical record of major alterations
      of trophic structure by revealing millennium-scale dietary shifts of brown bears
      (Ursus arctos) on the Hokkaido islands, Japan, using carbon, nitrogen, and sulfur
      stable isotope analysis. Dietary analysis of brown bears revealed that salmon
      consumption by bears in the eastern region of Hokkaido significantly decreased
      from 19% to 8%. In addition, consumption of terrestrial animals decreased from
      56% to 5% in western region, and 64% to 8% in eastern region. These dietary
      shifts are likely to have occurred in the last approximately 100-200 years, which
      coincides with the beginning of modernisation in this region. Our results suggest
      that human activities have caused an alteration in the trophic structure of brown
      bears in the Hokkaido islands. This alteration includes a major decline in the
      marine-terrestrial linkage in eastern region, and a loss of indirect-interactions
      between bears and wolves, because the interactions potentially enhanced deer
      predation by brown bears. 

PMID- 25776995
TI  - Outcome after surgical resection for duodenal adenocarcinoma in the UK.
AB  - BACKGROUND: Factors influencing long-term outcome after surgical resection for
      duodenal adenocarcinoma are unclear. METHODS: A prospectively created database
      was reviewed for patients undergoing surgery for duodenal adenocarcinoma in six
      UK hepatopancreaticobiliary centres from 2000 to 2013. Factors influencing
      overall survival and disease-free survival (DFS) were identified by regression
      analysis. RESULTS: Resection with curative intent was performed in 150 (84.3 per
      cent) of 178 patients. The postoperative morbidity rate for these patients was
      40.0 per cent and the in-hospital mortality rate was 3.3 per cent. Patients who
      underwent resection had a better median survival than those who had a palliative
      surgical procedure (84 versus 8 months; P < 0.001). The 1-, 3- and 5-year overall
      survival rates for patients who underwent resection were 83.9, 66.7 and 51.2 per
      cent respectively. Median DFS was 53 months, and 1- and 3-year DFS rates were
      80.8 and 56.5 per cent respectively. Multivariable analysis revealed that node
      status (hazard ratio 1.73, 95 per cent c.i. 1.07 to 2.79; P = 0.006) and
      lymphovascular invasion (hazard ratio 3.49, 1.83 to 6.64; P = 0.003) were
      associated with overall survival. CONCLUSION: Resection of duodenal
      adenocarcinoma in specialist centres is associated with good long-term survival.
      Lymphovascular invasion and nodal metastases are independent prognostic
      indicators.

PMID- 25776996
TI  - Correction: Genotoxicity of metal oxide nanomaterials: review of recent data and
      discussion of possible mechanisms.

PMID- 25776997
TI  - The utility of FloSeal haemostatic agent in the management of epistaxis.
AB  - BACKGROUND: FloSeal, a locally applied haemostatic agent, has been shown to be
      effective in a variety of clinical situations. This study investigated its
      potential benefits in the management of epistaxis. METHODS: The outcomes of a
      series of patients with epistaxis presenting to one ENT unit, over a two-month
      period, were compared. Patients were either treated with FloSeal or traditional
      epistaxis management techniques. Success of FloSeal was classed as complete
      haemostasis after its application, without the need for further interventions and
      no readmission with epistaxis within 7 days. RESULTS: Our study comprised 101
      adults, with a mean age of 70 years (range, 22-98 years). The overall success
      rate for FloSeal was 14 per cent (5 out of 36 cases). It was successful in 66 per
      cent of anterior epistaxis cases (2 out of 3) and in only 9 per cent of posterior
      epistaxis cases (3 out of 33). There was a significantly higher failure rate of
      FloSeal compared with nasal packing in posterior epistaxis (p < 0.001).
      CONCLUSION: Our findings suggest that FloSeal has a limited role in the
      management of epistaxis.

PMID- 25776998
TI  - Redox communication within multinuclear iron-sulfur complexes related to
      electronic interplay in the active site of [FeFe]hydrogenase.
AB  - The one-electron oxidations of a Fe2 complex lead to the formation of a
      persistent metal-stabilized thiyl radical Fe2 species, mixed-valent Fe4, and Fe8
      complexes. The unpaired spin in the Fe2 radical species delocalizes over the Fe2
      and the aromatic dithiolate, mostly on the terminal sulfur. The subsequent
      dimerization of the singly oxidized Fe2 to the Fe4 retains the partial thiyl
      radical character. For an analogue with less steric hindrance, the pi-pi stacking
      interaction between the dithiolato aromatic rings induces generation of the Fe8,
      in which process electronic structures of the species are modulated through
      reducing the thiyl radical to the thiolate. Electronic reorganization repeats
      when the Fe8 is converted to Fe4. Electronic interplay in the complexes decreases
      the energy gap of frontier MOs and buffers electronic impacts upon redox events.
      Easier accessible redox potentials and increased stability of the species are
      facilitated. The results demonstrate that electronic versatility of the
      benzenedithiolate exerts pronounced influences on electronic and coordination
      structure of the metal complexes.

PMID- 25777043
TI  - A gut solution for hepatic encephalopathy.

PMID- 25777042
TI  - Application of participatory ergonomics to the redesign of the family-centred
      rounds process.
AB  - Participatory ergonomics (PE) can promote the application of human factors and
      ergonomics (HFE) principles to healthcare system redesign. This study applied a
      PE approach to redesigning the family-centred rounds (FCR) process to improve
      family engagement. Various FCR stakeholders (e.g. patients and families,
      physicians, nurses, hospital management) were involved in different stages of the
      PE process. HFE principles were integrated in both the content (e.g. shared
      mental model, usability, workload consideration, systems approach) and process
      (e.g. top management commitment, stakeholder participation, communication and
      feedback, learning and training, project management) of FCR redesign. We describe
      activities of the PE process (e.g. formation and meetings of the redesign team,
      data collection activities, intervention development, intervention
      implementation) and present data on PE process evaluation. To demonstrate the
      value of PE-based FCR redesign, future research should document its impact on FCR
      process measures (e.g. family engagement, round efficiency) and patient outcome
      measures (e.g. patient satisfaction). 

PMID- 25777044
TI  - The importance (or lack thereof) of niche divergence to the maintenance of a
      northern species complex: the case of the long-toed salamander (Ambystoma
      macrodactylum Baird).
AB  - The relative importance of ecological vs. non-ecological factors for the origin
      and maintenance of species is an open question in evolutionary biology. Young
      lineages--such as the distinct genetic groups that make up the ranges of many
      northern species--represent an opportunity to study the importance of ecological
      divergence during the early stages of diversification. Yet, few studies have
      examined the extent of niche divergence between lineages in previously glaciated
      regions and the role of ecology in maintaining the contact zones between them. In
      this study, we used tests of niche overlap in combination with ecological niche
      models to explore the extent of niche divergence between lineages of the long
      toed salamander (Ambystoma macrodactylum Baird) species complex and to determine
      whether contact zones correspond to (divergent) niche limits. We found limited
      evidence for niche divergence between the different long-toed salamander
      lineages, substantial overlap in the predicted distribution of suitable climatic
      space for all lineages and range limits that are independent of niche limits.
      These results raise questions as to the importance of ecological divergence to
      the development of this widespread species complex and highlight the potential
      for non-ecological factors to play a more important role in the maintenance of
      northern taxa.

PMID- 25777045
TI  - Study for Updated Gout Classification Criteria: Identification of Features to
      Classify Gout.
AB  - OBJECTIVE: To determine which clinical, laboratory, and imaging features most
      accurately distinguished gout from non-gout. METHODS: We performed a cross
      sectional study of consecutive rheumatology clinic patients with >=1 swollen
      joint or subcutaneous tophus. Gout was defined by synovial fluid or tophus
      aspirate microscopy by certified examiners in all patients. The sample was
      randomly divided into a model development (two-thirds) and test sample (one
      third). Univariate and multivariate association between clinical features and
      monosodium urate-defined gout was determined using logistic regression modeling.
      Shrinkage of regression weights was performed to prevent overfitting of the final
      model. Latent class analysis was conducted to identify patterns of joint
      involvement. RESULTS: In total, 983 patients were included. Gout was present in
      509 (52%). In the development sample (n = 653), the following features were
      selected for the final model: joint erythema (multivariate odds ratio [OR] 2.13),
      difficulty walking (multivariate OR 7.34), time to maximal pain <24 hours
      (multivariate OR 1.32), resolution by 2 weeks (multivariate OR 3.58), tophus
      (multivariate OR 7.29), first metatarsophalangeal (MTP1) joint ever involved
      (multivariate OR 2.30), location of currently tender joints in other foot/ankle
      (multivariate OR 2.28) or MTP1 joint (multivariate OR 2.82), serum urate level >6
      mg/dl (0.36 mmoles/liter; multivariate OR 3.35), ultrasound double contour sign
      (multivariate OR 7.23), and radiograph erosion or cyst (multivariate OR 2.49).
      The final model performed adequately in the test set, with no evidence of misfit,
      high discrimination, and predictive ability. MTP1 joint involvement was the most
      common joint pattern (39.4%) in gout cases. CONCLUSION: Ten key discriminating
      features have been identified for further evaluation for new gout classification
      criteria. Ultrasound findings and degree of uricemia add discriminating value,
      and will significantly contribute to more accurate classification criteria.

PMID- 25777046
TI  - A robust and reproducible animal serum-free culture method for clinical-grade
      bone marrow-derived mesenchymal stromal cells.
AB  - Efficient xenofree expansion methods to replace fetal bovine serum (FBS)-based
      culture methods are strongly encouraged by the regulators and are needed to
      facilitate the adoption of mesenchymal stromal cell (MSC)-based therapies. In the
      current study we established a clinically-compliant and reproducible animal serum
      free culture protocol for bone marrow-(BM-) MSCs based on an optimized platelet
      derived supplement. Our study compared two different platelet-derived
      supplements, platelet lysate PL1 versus PL2, produced by two different methods
      and lysed with different amounts of freeze-thaw cycles. Our study also explored
      the effect of a low oxygen concentration on BM-MSCs. FBS-supplemented BM-MSC
      culture served as control. Growth kinetics, differentiation and immunomodulatory
      potential, morphology, karyotype and immunophenotype was analysed. Growth
      kinetics in long-term culture was also studied. Based on the initial results, we
      chose to further process develop the PL1-supplemented culture protocol at 20 %
      oxygen. The results from 11 individual BM-MSC batches expanded in the chosen
      condition were consistent, yielding 6.60 * 10(9) +/- 4.74 * 10(9) cells from only
      20 ml of bone marrow. The cells suppressed T-cell proliferation, displayed normal
      karyotype and typical MSC differentiation potential and phenotype. The BM-MSCs
      were, however, consistently HLA-DR positive when cultured in platelet lysate (7.5
      66.1 %). We additionally show that culture media antibiotics and sterile
      filtration of the platelet lysate can be successfully omitted. We present a
      robust and reproducible clinically-compliant culture method for BM-MSCs based on
      platelet lysate, which enables high quantities of HLA-DR positive MSCs at a low
      passage number (p2) and suitable for clinical use. 

PMID- 25777047
TI  - Dynamic 3D culture: models of chondrogenesis and endochondral ossification.
AB  - The formation of cartilage from stem cells during development is a complex
      process which is regulated by both local growth factors and biomechanical cues,
      and results in the differentiation of chondrocytes into a range of subtypes in
      specific regions of the tissue. In fetal development cartilage also acts as a
      precursor scaffold for many bones, and mineralization of this cartilaginous bone
      precursor occurs through the process of endochondral ossification. In the
      endochondral formation of bones during fetal development the interplay between
      cell signalling, growth factors, and biomechanics regulates the formation of load
      bearing bone, in addition to the joint capsule containing articular cartilage and
      synovium, generating complex, functional joints from a single precursor anlagen.
      These joint tissues are subsequently prone to degeneration in adult life and have
      poor regenerative capabilities, and so understanding how they are created during
      development may provide useful insights into therapies for diseases, such as
      osteoarthritis, and restoring bone and cartilage lost in adulthood. Of particular
      interest is how these tissues regenerate in the mechanically dynamic environment
      of a living joint, and so experiments performed using 3D models of cartilage
      development and endochondral ossification are proving insightful. In this review,
      we discuss some of the interesting models of cartilage development, such as the
      chick femur which can be observed in ovo, or isolated at a specific developmental
      stage and cultured organotypically in vitro. Biomaterial and hydrogel-based
      strategies which have emerged from regenerative medicine are also covered,
      allowing researchers to make informed choices on the characteristics of the
      materials used for both original research and clinical translation. In all of
      these models, we illustrate the essential importance of mechanical forces and
      mechanotransduction as a regulator of cell behavior and ultimate structural
      function in cartilage.

PMID- 25777048
TI  - Detection of major climatic and environmental predictors of liver fluke exposure
      risk in Ireland using spatial cluster analysis.
AB  - Fasciolosis caused by Fasciola hepatica (liver fluke) can cause significant
      economic and production losses in dairy cow farms. The aim of the current study
      was to identify important weather and environmental predictors of the exposure
      risk to liver fluke by detecting clusters of fasciolosis in Ireland. During
      autumn 2012, bulk-tank milk samples from 4365 dairy farms were collected
      throughout Ireland. Using an in-house antibody-detection ELISA, the analysis of
      BTM samples showed that 83% (n=3602) of dairy farms had been exposed to liver
      fluke. The Getis-Ord Gi* statistic identified 74 high-risk and 130 low-risk
      significant (P<0.01) clusters of fasciolosis. The low-risk clusters were mostly
      located in the southern regions of Ireland, whereas the high-risk clusters were
      mainly situated in the western part. Several climatic variables (monthly and
      seasonal mean rainfall and temperatures, total wet days and rain days) and
      environmental datasets (soil types, enhanced vegetation index and normalised
      difference vegetation index) were used to investigate dissimilarities in the
      exposure to liver fluke between clusters. Rainfall, total wet days and rain days,
      and soil type were the significant classes of climatic and environmental
      variables explaining the differences between significant clusters. A discriminant
      function analysis was used to predict the exposure risk to liver fluke using 80%
      of data for modelling and the remaining subset of 20% for post hoc model
      validation. The most significant predictors of the model risk function were total
      rainfall in August and September and total wet days. The risk model presented
      100% sensitivity and 91% specificity and an accuracy of 95% correctly classified
      cases. A risk map of exposure to liver fluke was constructed with higher
      probability of exposure in western and north-western regions. The results of this
      study identified differences between clusters of fasciolosis in Ireland regarding
      climatic and environmental variables and detected significant predictors of the
      exposure risk to liver fluke.

PMID- 25777049
TI  - Evaluation of a single-stage consumable-free modulator for comprehensive two
      dimensional gas chromatography: analysis of polychlorinated biphenyls,
      organochlorine pesticides and chlorobenzenes.
AB  - Comprehensive two-dimensional gas chromatography (GC*GC) has been rapidly growing
      in popularity. The GC*GC separation is performed by interfacing a modulator
      between two columns of different selectivities. The modulator periodically traps
      and then re-injects the analytes eluting from the first column into the second
      column. The most popular GC*GC systems require consumables such as liquid N2 for
      the trapping function of the modulator. Although these systems are very
      effective, their costs are a hindrance to more widespread use. A new, single
      stage thermal modulator for GC*GC that requires no consumables has been developed
      and tested. The device traps analytes using a proprietary stainless steel
      capillary trap compressed between two ceramic cooling pads. Analytes are
      thermally desorbed from the trap into the second column via resistive heating. To
      evaluate this system, a routine accredited method for the analysis of
      polychlorinated biphenyls, organochlorine pesticides and chlorobenzenes was run
      using the new modulator and its performance was compared to that of an industry
      standard modulation system. Within-day repeatability (% RSD ranging from 2% to
      13%), between-day reproducibility (% RSD from 3% to 15%), as well as between-trap
      reproducibility were assessed. The results are very encouraging as negligible
      shifts in retention times (% RSD from 0.3% to 0.6% in the 1st dimension and 0.8%
      to 2% in the 2nd dimension) were observed for both within-day and day-to-day
      comparisons of the studied samples (ANOVA, p=0.9893 for the sediment reference
      material compared), and the quantitative results were comparable. Routine
      analysis and quality control applications will benefit from the improved
      reproducibility as the variances in cold/hot jet flows and temperatures are
      eliminated. An overview of the device operation and the results from this study
      are summarized. 

PMID- 25777050
TI  - Determining cyclooxygenase-2 activity in three different test systems utilizing
      online-solid phase extraction-liquid chromatography-mass spectrometry for
      parallel quantification of prostaglandin E(2), D(2) and thromboxane B(2).
AB  - Cyclooxygenase-2 (COX-2) catalyzes the formation of PGH2 from arachidonic acid.
      PGH2 is further converted to different prostaglandins (PG), such as PGE2, PGD2
      and TxB2. In this study a rapid online-SPE-LC-MS method for the simultaneous
      quantification of PGE2, PGD2 and TxB2 streamlined for COX-2 enzyme assays is
      presented. Baseline separation of all analytes was achieved in only 7.1 min per
      sample, including sample preparation by online SPE. The method showed high
      sensitivity (LODs of 0.65-1.25 fmol on column) and accuracy (89-113%) in protein
      containing media. Because of online-SPE, no manual sample preparation was
      required, except for addition of IS solution, allowing to use the approach as
      rapid read-out in COX-2 activity assays. This was demonstrated by applying the
      method on three in vitro test systems: a cell-free enzyme assay, an assay using
      HCA-7 cells constitutively expressing COX-2 and primary human monocytes. In these
      assays, the potency of three popular drugs celecoxib, indomethacin and
      dexamethasone was successfully characterized with the new online-LC-MS method.
      The comparison of the results showed that the inhibitory effects of PG formation
      strongly depend on the test system. Thus we suggest that the modulation of COX-2
      activity of a test compound should be at least characterized in two assay
      systems. With the online-SPE-LC-MS described in here we present a versatile tool
      as read-out for these types of assays.

PMID- 25777051
TI  - Chromatographic performance of synthetic polycrystalline diamond as a stationary
      phase in normal phase high performance liquid chromatography.
AB  - The chromatographic properties of high pressure high temperature synthesised
      diamond (HPHT) are investigated in normal phase mode of high performance liquid
      chromatography. Purified nonporous irregular shape particles of average particles
      size 1.2 MUm and specific surface area 5.1 m(2) g(-1) were used for packing
      100*4.6 mm ID or 50*4.6 mm ID stainless steel columns. The retention behaviour of
      several classes of compounds including alkyl benzenes, polyaromatic hydrocarbons
      (PAH), alkylphenylketones, phenols, aromatic acids and bases were studied using n
      hexane-2-propanol mixtures as mobile phase. The results are compared with those
      observed for microdispersed sintered detonation nanodiamond (MSDN) and porous
      graphitic carbon (PGC). HPHT diamond revealed distinctive separation selectivity,
      which is orthogonal to that observed for porous graphitic carbon; while
      selectivities of HPHT diamond and microdispersed sintered detonation nanodiamonds
      are similar. Owing to non-porous particle nature, columns packed with high
      pressure high temperature diamond exhibited excellent mass transfer and produce
      separations with maximum column efficiency of 128,200 theoretical plates per
      meter.

PMID- 25777054
TI  - Polysomnography for the diagnosis of sleep disordered breathing in children under
      2 years of age.
AB  - OBJECTIVES: To describe clinical polysomnography (PSG) results, sleep physicians'
      diagnosis, and treatment of sleep disorder breathing in children less than 2
      years of age. STUDY DESIGN: Retrospective clinical chart review at a pediatric
      tertiary care center, pediatric sleep laboratory. SUBJECT SELECTION: Children
      less than 2 years of age who underwent clinical PSG over a 3-year period.
      METHODOLOGY: PSG results and physician interpretations were identified for
      inclusions. Children were excluded if either PSG results or physician
      interpretations were unavailable for review. Infants were classified in three age
      groups for comparison: <6 months, 6-12 months, and >12 months. RESULTS: Matched
      records were available for 233 PSGs undertaken at a mean age 11.1 +/- 7.0 months;
      31% were <6 months, 23% were 6-12 months, and 46% were 12-24 months of age.
      Infants <6 months showed significant differences on sleep parameters and
      respiratory indicators compared to other groups. Compared to physician sleep
      disordered breathing (SDB) classification, current pediatric apnea-hypopnea index
      (AHI)-based SDB severity classification overestimated SDB severity. Age and
      obstructive-mixed AHI (OMAHI) were most closely associated with physician
      identification of SDB. CONCLUSION: Children <6 months of age appear to represent
      a distinct group with respect to PSG. Experienced sleep physicians appear to
      incorporate age and respiratory event frequently when determining the presence of
      SDB. Further information about clinical significance of apnea in infancy is
      required, assisted by identification of factors that sleep physicians use to
      identify SDB in children <6 months of age.

PMID- 25777055
TI  - Cdc42: Role in Cancer Management.
AB  - Contribution of Cdc42, a member of Rho family, has been characterized for the
      beginning of variety of cellular responses including cellular transformation,
      cell division, cell invasion, migration, invadopodia formation, enzyme activity,
      filopodia formation, and cell polarity in cells. Deregulation of Cdc42 can alter
      the normal functioning of the cells, responsible for the initiation of signaling
      pathways and is correlated with several pathogenic processes such as cancer.
      Therefore, maintaining the level of Cdc42 and its effectors in cells, tumor
      progression can be controlled. Therefore, it can be suggested that deeper
      understanding about the Cdc42 contribution in cancer cell progression at
      molecular level can approach to the development of Cdc42 inhibitors in cancer
      management. 

PMID- 25777056
TI  - Early risk; late reward?

PMID- 25777057
TI  - Long-term results after lung transplantation using organs from circulatory death
      donors: a propensity score-matched analysis?.
AB  - OBJECTIVES: Due to organ shortage in lung transplantation (LTx), donation after
      circulatory death (DCD) has been implemented in several countries, contributing
      to an increasing number of organs transplanted. We sought to assess long-term
      outcomes after LTx with organs procured following circulatory death in comparison
      with those obtained from donors after brain death (DBD). METHODS: Between January
      2007 and November 2013, 302 LTxs were performed in our institution, whereby 60
      (19.9%) organs were retrieved from DCD donors. We performed propensity score
      matching (DCD:DBD = 1:2) based on preoperative donor and recipient factors that
      were significantly different in univariate analysis. RESULTS: After propensity
      matching, there were no statistically significant differences between the groups
      in terms of demographics and preoperative donor and recipient characteristics.
      There were no significant differences regarding intraoperative variables and
      total ischaemic time. Patients from the DCD group had significantly higher
      incidence of primary graft dysfunction grade 3 at the end of the procedure (P =
      0.014), and significantly lower pO2/FiO2 ratio during the first 24 h after the
      procedure (P = 0.018). There was a trend towards higher incidence of the need for
      postoperative extracorporeal life support in the DCD group. Other postoperative
      characteristics were comparable. While the overall cumulative survival was not
      significantly different, the DCD group had significantly poorer results in terms
      of bronchiolitis obliterans syndrome (BOS)-free survival in the long-term follow
      up. CONCLUSIONS: Long-term results after LTx with organs procured following DCD
      are in general comparable with those obtained after DBD LTx. However, patients
      transplanted using organs from DCD donors have a predisposition for development
      of BOS in the longer follow-up.

PMID- 25777058
TI  - Monitoring Inflammation, Humoral and Cell-mediated Immunity in Pancreas and Islet
      Transplants.
AB  - Type 1 diabetes (T1D) is caused by the chronic autoimmune destruction of insulin
      producing beta cells. Beta cell replacement therapy through whole pancreas or
      islet transplantation is a therapeutic option for patients in which a stable
      glucose control is not achievable with exogenous insulin therapy. Long-term
      insulin independence is, however, hampered by the recipient immune response that
      includes activation of inflammatory pathways and specific allo- and autoimmunity.
      The identification and monitoring of soluble and cellular biomarkers are of
      critical relevance for the prediction of graft damage, for the evaluation of
      responses to immune-modulating therapy, and for target pathways identification to
      generate novel drugs or therapeutic approaches. The final objective of immune
      monitoring is to find ways to improve the outcome of pancreas and islet
      transplantation. In this review, we discuss the available tools to monitor the
      innate, humoral and cellular responses after islet and pancreas transplantation,
      and the most relevant findings generated by these measurements. 

PMID- 25777059
TI  - Strategies to engineer tendon/ligament-to-bone interface: Biomaterials, cells and
      growth factors.
AB  - Integration between tendon/ligament and bone occurs through a specialized tissue
      interface called enthesis. The complex and heterogeneous structure of the
      enthesis is essential to ensure smooth mechanical stress transfer between bone
      and soft tissues. Following injury, the interface is not regenerated, resulting
      in high rupture recurrence rates. Tissue engineering is a promising strategy for
      the regeneration of a functional enthesis. However, the complex structural and
      cellular composition of the native interface makes enthesis tissue engineering
      particularly challenging. Thus, it is likely that a combination of biomaterials
      and cells stimulated with appropriate biochemical and mechanical cues will be
      needed. The objective of this review is to describe the current state-of-the-art,
      challenges and future directions in the field of enthesis tissue engineering
      focusing on four key parameters: (1) scaffold and biomaterials, (2) cells, (3)
      growth factors and (4) mechanical stimuli. 

PMID- 25777060
TI  - Unveiling privacy: advances in microtomography of coralline algae.
AB  - Marine calcareous algae are widespread in oceans of the world and known for their
      calcified cell walls and the generation of rhodolith beds that turn sandy bottoms
      into a complex structured ecosystem with high biodiversity. Rhodoliths are
      unattached, branching, crustose benthic marine red algae; they provide habitat
      for a rich variety of marine invertebrates. The resultant excavation is relevant
      to sediment production, while is common that the fragments or the whole specimens
      result in vast fossil deposits formed by rich material that can be "mined" for
      biological and geological data. Accordingly, microtomography (MUCT) may enable a
      detailed investigation of biological and geological signatures preserved within
      the rhodolith structure in a non-destructive approach that is especially relevant
      when analyzing herbaria collections or rare samples. Therefore, we prepared
      coralline algae samples and submitted them to a range of capabilities provided by
      the SkyScan1176 micro-CT scanner, including reconstruction, virtual slicing, and
      pinpointing biological and geological signatures. To this end, polychaetes and
      mollusk shells, or their excavations, coral nucleation, sediment deposits and
      conceptacles were all observed. Although a similar technique has been applied
      previously to samples of living rhodoliths in Brazil, we show, for the first
      time, its successful application to fossil rhodoliths. We also provide a detailed
      working protocol and discuss the advantages and limitations of the
      microtomography within the rhodoliths. 

PMID- 25777061
TI  - Modulation of temporal summation threshold of the nociceptive withdrawal reflex
      by transcutaneous spinal direct current stimulation in humans.
AB  - OBJECTIVE: Transcutaneous spinal direct current stimulation (tsDCS) modulates
      spinal cord pain pathways. The study is aimed to clarify the neurophysiology of
      the tsDCS-induced modulation of the spinal cord pain processing by evaluating the
      effect of the tsDCS on temporal summation threshold (TST) of the nociceptive
      withdrawal reflex (NWR). METHODS: In a randomized, double-blind, crossover study
      the effects of anodal, cathodal and sham tsDCS (2 mA, 15 min) applied on the skin
      overlying the thoracic spinal cord were investigated in 10 healthy subjects.
      RESULTS: Anodal tsDCS induced a long-lasting (up to 60 min) increase in TST of
      the NWR as well as a parallel decrease in related psychophysical temporal
      summation of pain, while cathodal and sham tsDCS resulted ineffective.
      CONCLUSIONS: Anodal tsDCS represents a non-invasive tool able to induce an early
      and long-lasting depression of the transitory facilitation of the wide dynamic
      range neurons activity at the basis of both the temporal summation of the NWR and
      the related temporal summation of pain sensation. SIGNIFICANCE: The modulation of
      the temporal processing of nociceptive stimuli could be effective in treating
      clinical pain conditions in which pain is generated by spinal cord structures.

PMID- 25777062
TI  - Characterization of the intrarenal renin-angiotensin system in experimental
      alport syndrome.
AB  - Blockade of the renin-angiotensin system attenuates the progression of
      experimental and clinical Alport syndrome (AS); however, the underlying
      mechanism(s) remains largely unknown. We evaluated the renin-angiotensin system
      in 4- and 7-week-old homozygous for collagen, type IV, alpha3 gene (Col4A3(-/-))
      and wild-type mice, a model of AS characterized by proteinuria and progressive
      renal injury. Renal angiotensin (Ang) II levels increased, whereas renal Ang-(1
      7) levels decreased in 7-week-old Col4a3(-/-) mice compared with age-matched
      controls; these changes were partially reversed by recombinant angiotensin
      converting enzyme 2 (ACE2) treatment. The expression of both the angiotensinogen
      and renin protein increased in Col4a3(-/-) compared with wild-type mice.
      Consistent with the Ang-(1-7) levels, the expression and activity of kidney ACE2
      decreased in 7-week-old Col4a3(-/-) mice. The urinary excretion rate of ACE2
      paralleled the decline in tissue expression. Expression of an Ang II-induced
      gene, heme oxygenase-1, was up-regulated in the kidneys of 7-week-old Col4a3(-/-)
      mice compared with wild-type mice by microarray analysis. Heme oxygenase-1 (HO-1)
      protein expression was increased in kidneys of Col4a3(-/-) mice and normalized by
      treatment with ACE inhibitor. Urinary HO-1 excretion paralleled renal HO-1
      expression. In conclusion, progressive kidney injury in AS is associated with
      changes in expression of intrarenal renin Ang system components and Ang peptides.
      HO-1 and ACE2 may represent novel markers of AS-associated kidney injury, whereas
      administration of recombinant ACE2 and/or Ang-(1-7) may represent novel
      therapeutic approaches in AS.

PMID- 25777063
TI  - Senescence may mediate conversion of tau phosphorylation-induced apoptotic escape
      to neurodegeneration.
AB  - Neurodegeneration is the characteristic pathology in the brains of Alzheimer's
      disease (AD). However, the nature and molecular mechanism leading to the
      degeneration are not clarified. Given that only the neurons filled with
      neurofibrillary tangles survive to the end stage of the disease and the major
      component of the tangles is the hyperphosphorylated tau proteins, it is
      conceivable that tau hyperphosphorylation must play a crucial role in AD
      neurodegeneration. We have demonstrated that tau hyperphosphorylation renders the
      cells more resistant to the acute apoptosis. The molecular mechanisms involve
      substrate competition of tau and beta-catenin for glycogen synthase kinase 3beta
      (GSK-3beta); activation of Akt; preservation of Bcl-2 and suppression of Bax,
      cytosolic cytochrome-c, and caspase-3 activity; and upregulation of unfolded
      protein response (UPR), i.e., up-regulating phosphorylation of PERK, eIF2 and
      IRE1 with an increased cleavage of ATF6 and ATF4. On the other hand, tau
      hyperphosphorylation promotes its intracellular accumulation and disrupts axonal
      transport; hyperphosphorylated tau also impairs cholinergic function and inhibits
      proteasome activity. These findings indicate that tau hyperphosphorylation and
      its intracellular accumulation play dual role in the evolution of AD. We
      speculate that transient tau phosphorylation helps cells abort from an acute
      apoptosis, while persistent tau hyperphosphorylation/accumulation may trigger
      cell senescence that eventually causes a chronic neurodegeneration. Therefore,
      the nature of "AD neurodegeneration" may represent a new type of tau-regulated
      chronic neuron death; and the stage of cell senescence may provide a broad window
      for the intervention of AD. 

PMID- 25777064
TI  - Performance of aerobic granular sludge in a sequencing batch bioreactor for
      slaughterhouse wastewater treatment.
AB  - Lab-scale experiment was conducted to investigate the formation and
      characteristics of aerobic granular sludge for biological nutrient removal of
      slaughterhouse wastewater. Experimental results showed that removal performances
      of chemical oxygen demand (COD), ammonia and phosphate were enhanced with sludge
      granulation, and their removal efficiencies reached 95.1%, 99.3% and 83.5%,
      respectively. The aerobic granular sludge was matured after 90days cultivation,
      and protein-like substances were the main components. Simultaneously, the mass
      ratio of proteins and polysaccharides (PN/PS) was enhanced to 2.5 from 1.7. The
      granules with particle sizes of 0.6-1.2 and 1.2-1.8mm, accounting for 69.6%, were
      benefit for the growth of ammonia oxidizing bacteria (AOB) and nitrate oxidizing
      bacteria (NOB), and corresponding specific oxygen demand rates (SOUR) of AOB and
      NOB were 31.4 and 23.3mgO2/gMLSSh, respectively. 

PMID- 25777065
TI  - Production of DagA and ethanol by sequential utilization of sugars in a mixed
      sugar medium simulating microalgal hydrolysate.
AB  - A novel two-step fermentation process using a mixed-sugar medium mimicking
      microalgal hydrolysate has been proposed to avoid glucose repression and thus to
      maximize substrate utilization efficiency. When DagA, a beta-agarase was produced
      in one step in the mixed-sugar medium by using a recombinant Streptomyces
      lividans, glucose was found to have negative effects on the consumption of the
      other sugars and DagA biosynthesis causing low substrate utilization efficiency
      and low DagA productivity. To overcome such difficulties, a new strategy of
      sequential substrate utilization was developed. In the first step, glucose was
      consumed by Saccharomyces cerevisiae together with galactose and mannose
      producing ethanol, after which DagA was produced from the remaining sugars of
      xylose, rhamnose and ribose. Fucose was not consumed. By adopting this two-step
      process, the overall substrate utilization efficiency was increased approximately
      3-fold with a nearly 2-fold improvement of DagA production, let alone the
      additional benefit of ethanol production. 

PMID- 25777066
TI  - Enhancing the production of eicosapentaenoic acid (EPA) from Nannochloropsis
      oceanica CY2 using innovative photobioreactors with optimal light source
      arrangements.
AB  - Binary combinations of LEDs with four different colors were used as light sources
      to identify the effects of multiple wavelengths on the production of
      eicosapentaenoic acid (EPA) by an isolated microalga Nannochloropsis oceanica
      CY2. Combining LED-Blue and LED-Red could give the highest EPA productivity of
      13.24 mg L(-1) d(-1), which was further enhanced to 14.4 mg L(-1) d(-1) when
      using semi-batch operations at a 40% medium replacement ratio. A novel
      photobioreactor with additional immersed light sources improved light penetration
      efficiency and led to an 38% (0.170-0.235 g L(-1) d(-1)) increase in the
      microalgae biomass productivity and a 9% decrease in electricity consumption
      yield of EPA (10.15-9.33 kW-h (g EPA)(-1)) when compared with the control (i.e.,
      without immersed light sources). Operating the immersed LEDs at a flashing
      frequency of 9 Hz further lowered the energy consumption yield to 8.87 kW-h (g
      EPA)(-1).

PMID- 25777067
TI  - Hydrolysis of biomass using a reusable solid carbon acid catalyst and
      fermentation of the catalytic hydrolysate to ethanol.
AB  - Solid acid catalysts can hydrolyze cellulose with lower reaction times and are
      easy to recover and reuse. A glycerol based carbon acid catalyst developed at
      CSIR-IICT performed well in acid catalysis reactions and hence this study was
      undertaken to evaluate the catalyst for hydrolysis of biomass (alkali pretreated
      or native rice straw). The catalyst could release 262 mg/g total reducing sugars
      (TRS) in 4h at 140  degrees C from alkali pretreated rice straw, and more
      importantly it released 147 mg/g TRS from native biomass. Reusability of the
      catalyst was also demonstrated. Catalytic hydrolysate was used as sugar source
      for fermentation to produce ethanol. Results indicate the solid acid catalyst as
      an interesting option for biomass hydrolysis.

PMID- 25777068
TI  - Rotavirus seasonality in urban sewage from Argentina: effect of meteorological
      variables on the viral load and the genetic diversity.
AB  - In Argentina, the rotavirus disease exhibits seasonal variations, being most
      prevalent in the fall and winter months. To deepen the understanding of rotavirus
      seasonality in our community, the influence of meteorological factors on the
      rotavirus load and the genetic diversity in urban raw sewage from Cordoba city,
      Argentina were evaluated. Wastewater samples were collected monthly during a
      three-year study period and viral particles were concentrated by polyethylene
      glycol precipitation. RT-nested PCR was applied for rotavirus detection, and
      VP7/VP4 characterization and real-time PCR for rotavirus quantification. Both
      molecular techniques showed relatively similar sensitivity rates and revealed
      rotavirus presence in urban wastewater in cold and warm seasons, indicating its
      circulation in the local community all year round. However, a slight trend for
      rotavirus circulation was noted by real-time PCR in the fall and winter seasons,
      showing a significantly higher peak of rotavirus concentration at mean
      temperatures lower than 18 degrees C and also higher, although not statistically
      different during drier weather. VP7 and VP4 gene characterization showed that G1
      and P[8] genotypes were dominant, and temporal variations in genotype
      distribution were not observed. Rotavirus spread is complex and our results point
      out that weather factors alone cannot explain the seasonal quantitative pattern
      of the rotavirus disease. Therefore, alternative transmission routes, changes in
      human behavior and susceptibility, and the stability and survivability of the
      virus might all together contribute to the seasonality of rotavirus. The results
      obtained here provide evidence regarding the dynamics of rotavirus circulation
      and maintenance in Argentina. 

PMID- 25777069
TI  - Efficacy and safety of limus-eluting versus paclitaxel-eluting coronary artery
      stents in patients with diabetes mellitus: A meta-analysis.
AB  - BACKGROUND/OBJECTIVES: The relative efficacy and safety of limus-eluting stent
      (LES) versus paclitaxel-eluting stent (PES) in DM patients remain unclear.
      METHODS: The PubMed, EMBASE, and Cochrane Central Register of Controlled Trials
      electronic databases were searched from January 2001 to December 2013. Clinical
      trials that performed head-to-head comparisons of LES versus PES implantation in
      patients with DM were considered for inclusion. RESULTS: This meta-analysis
      included 28 clinical trials involving 23,678 patients: 9953 who underwent
      sirolimus-eluting stent (SES) implantation, 4209 underwent everolimus-eluting
      stent (EES) or zotarolimus-eluting stent (ZES) implantation, and 9516 underwent
      PES implantation. The short-term target lesion revascularization (TLR) rate was
      significantly lower after SES implantation than after PES implantation (3.6% vs
      6.3%; odds ratio (OR): 0.659; P=0.014), but there were no significant differences
      in the rates of target vessel revascularization (TVR), stent thrombosis (ST),
      myocardial infarction (MI), all-cause mortality, or major adverse cardiac events
      (MACE). There were no differences in the longer-term rates of TLR, TVR, ST, MI,
      all-cause mortality, or MACE between SES versus PES. Second-generation LES (EES
      or ZES) implantation resulted in lower rates of ST (2.1% vs 3.3%; OR: 0.586;
      P<0.001), MI (2.3% vs 4.1%; OR: 0.527; P=0.001), and MACE (8.0% vs 10.3%; OR:
      0.796; P=0.007) than PES implantation. CONCLUSIONS: In patients with DM, short-
      and longer-term MACE rates were similar after first-generation LES and PES
      implantation. The second-generation LES may be better than PES implantation in
      rates of ST, MI, and MACE.

PMID- 25777070
TI  - Hyperuricemia is independently associated with increased risk of atrial
      fibrillation: A meta-analysis of cohort studies.

PMID- 25777071
TI  - Interrelated aldosterone and parathyroid hormone mutually modify cardiovascular
      mortality risk.
AB  - BACKGROUND: Inappropriate aldosterone and parathyroid hormone (PTH) secretion is
      associated with increased cardiovascular risk. Accumulating evidence suggests
      bidirectional interplay between aldosterone and PTH. METHODS: We evaluated the
      cross-sectional relationship between plasma aldosterone concentration (PAC),
      aldosterone to renin ratio (ARR) and PTH and subsequently tested whether the
      interaction between PAC and PTH modified the risk of cardiovascular death. PAC
      [78.0 (48.0-123.0) pg/mL], ARR [6.4 (2.9-12.9) pg/mL/pg/mL] and PTH concentration
      [median: 29.0 (22.0-40.0) pg/mL] were measured in 3074 patients (mean age: 62.5
      +/- 10.6 years; 30.3% women) referred to coronary angiography in a tertiary care
      center in Southwest Germany. RESULTS: Using multiple linear regression analysis,
      PAC and ARR emerged as an independent predictor of higher PTH concentrations
      (beta=0.12 and 0.21, P<0.001 for both) irrespective of intake of antihypertensive
      treatment, 25(OH)D, kidney function, serum calcium, phosphate, magnesium,
      cortisol, NT-pro-BNP, soluble alpha-klotho and FGF-23 concentration. After a
      median follow-up of 9.9 years, 512 (16.7%) participants had died due to fatal
      cardiovascular events. Multivariate Cox proportional hazard analysis revealed
      that both PAC and PTH were independently associated with cardiovascular
      mortality, with a potential synergistic interaction (P=0.028). PAC and PTH are
      exclusively associated with cardiovascular death in subjects with PTH and PAC
      concentrations above the median, respectively (PAC: HR per log SD: 1.14; 95% CI
      1.02-1.29; P=0.026; PTH: HR per log SD: 1.18; 95% CI 1.02-1.37; P=0.031).
      CONCLUSIONS: Higher PAC and ARR were independently associated with PTH. PAC was
      independently related to incident cardiovascular mortality exclusively in
      patients with elevated PTH and vice versa.

PMID- 25777072
TI  - The Altered Brain Activation of Phonological Working Memory, Dual Tasking, and
      Distraction Among Participants With Adult ADHD and the Effect of the MAOA
      Polymorphism.
AB  - OBJECTIVE: The present study aimed to reveal the brain correlates of phonological
      working memory (WM), dual tasking, and distraction in adult ADHD combined with
      the effect of polymorphisms of monoamine oxidase A ( MAOA rs1137070 Asp470Asp).
      METHOD: A total of 29 participants with adult ADHD and 21 controls were
      recruited. They completed 0-back and 2-back tasks, as wells as 2-back tasks with
      a dual-task effect or a distracting effect, during functional magnetic resonance
      imaging scanning. RESULTS: The brain activation of WM in the bilateral inferior
      frontal lobe, pars opercularis, was higher among the adult ADHD group. The
      genotype of MAOA significantly interacted with the ADHD effect in the left
      inferior frontal lobe, pars opercularis. Adults with ADHD had higher activation
      in the left lingual area in response to the dual-tasking effect. CONCLUSION: The
      MAOA polymorphism moderated the altered activation in pars opercularis for WM
      among adults with ADHD. The higher lingual gyrus activation might indicate that
      higher attention resources are demanded to sustain the dual-task function of
      adults with ADHD.

PMID- 25777073
TI  - Negative Consequences of Poor Driving Outcomes Reported by Adolescents With and
      Without ADHD.
AB  - OBJECTIVE: Although adolescents with ADHD report less driving experience, a
      greater proportion of adolescents with ADHD report receiving at least one ticket;
      however, no study has examined the severity of infractions committed by
      adolescent drivers with ADHD. METHOD: A total of 61 adolescents (28 ADHD, 33
      controls) aged 16 to 17 with a valid driver's license completed a self-report
      Driving History Questionnaire (DHQ), which asked about months of driving
      experience, negative driving outcomes, and severity of consequences. RESULTS: A
      greater proportion of adolescents with ADHD reported receiving fines, points on
      their driver's license, and remedial driving class. Furthermore, adolescents with
      ADHD reported attending a greater number of hours in remedial driving class, and
      a greater expense associated with fines. CONCLUSION: Importantly, ADHD-related
      negative driving outcomes manifest early in driving careers. Furthermore,
      increased negative consequences of poor and/or risky driving among adolescents
      with ADHD were evident despite having fewer months of independent driving.

PMID- 25777074
TI  - [Remove polyps and discard? Resist the beginnings!].

PMID- 25777075
TI  - [Molecular pathology of colorectal cancer].
AB  - In recent years, several predictive and prognostic biomarkers have been
      established in colorectal cancer (CRC). The RAS-mutation status is widely applied
      in the daily routine diagnostic as predictive biomarker for treatment with EGFR
      inhibitors. A BRAF- mutation has no predictive value in this context. The
      detection of high-grade microsatellite instability (MSI-H) is a predictive
      biomarker for response to 5-Fluoruracil-monotherapy. Prognostic biomarkers in CRC
      are the MSI-status and the mutational status of BRAF. According to the current
      WHO classification poorly and undifferentiated CRC and MSI-associated special
      morphological subtypes are molecular graded depending on their MSI-status. The
      detection of a BRAF-mutation in the context of microsatellite stability (MSS) is
      associated with a very poor prognosis and thus represents the most aggressive
      molecular subtype of CRC. In patients with positive Bethesda criteria a stepwise
      immunohistochemical and molecular diagnostic scheme is proposed. 

PMID- 25777076
TI  - Intra-tester and inter-tester reliability of post-occlusive reactive hyperaemia
      measurement at the hallux.
AB  - BACKGROUND: Post-occlusive reactive hyperaemia (PORH) is a measurement of the
      vasodilatory capacity of the microvasculature that is associated with
      cardiovascular disease, peripheral arterial disease and foot ulceration. The
      reliability of its measurement in the hallux (great toe) for clinical and
      research purposes has not been adequately assessed. This study assesses both the
      intra-tester reliability and inter-tester reliability of four methods of
      assessing PORH in the hallux. METHODS AND RESULTS: A within-subject repeated
      measures design was used. Forty-two participants underwent PORH testing using
      four methods: pressure measurement with photoplethysmography; an automated laser
      Doppler technique with local heating; an automated laser Doppler technique
      without local heating; and a manual laser Doppler technique. Participants
      underwent testing on two occasions with a three to 14 day interval. Laser Doppler
      measurement with a heating probe was found to be the most reliable method of PORH
      measurement. The index of the area under the curve pre- and post-occlusion and
      peak perfusion as a percentage of baseline were the most reliable variables.
      CONCLUSIONS: PORH can be reliably measured using laser Doppler when combined with
      a heating probe. Further research is required to determine the clinical utility
      of photoplethysmography in the measurement of PORH.

PMID- 25777077
TI  - Oxygen tension affects histone remodeling of in vitro-produced embryos in a
      bovine model.
AB  - In vitro production of bovine embryos is a biotechnology of great economic
      impact. Epigenetic processes, such as histone remodeling, control gene expression
      and are essential for proper embryo development. Given the importance of IVP as a
      reproductive biotechnology, the role of epigenetic processes during embryo
      development, and the important correlation between culture conditions and
      epigenetic patterns, the present study was designed as a 2 * 2 factorial to
      investigate the influence of varying oxygen tensions (O2; 5% and 20%) and
      concentrations of fetal bovine serum (0% and 2.5%), during IVC, in the epigenetic
      remodeling of H3K9me2 (repressive) and H3K4me2 (permissive) in bovine embryos.
      Bovine oocytes were used for IVP of embryos, cleavage and blastocyst rates were
      evaluated, and expanded blastocysts were used for evaluation of the histone marks
      H3K9me2 and H3K4me2. Morulae and expanded blastocysts were also used to evaluate
      the expression of remodeling enzymes, specific to the aforementioned marks, by
      real-time polymerase chain reaction. Embryos produced in the presence of fetal
      bovine serum (2.5%) had a 10% higher rate of blastocyst formation. Global
      staining for the residues H3K9me2 and H3K4me2 was not affected significantly by
      the presence of serum. Notwithstanding, the main effect of oxygen tension was
      significant for both histone marks, with both repressive and permissive marks
      being higher in embryos cultured at the higher oxygen tension; however,
      expression of the remodeling enzymes did not differ in morulae or blastocysts in
      response to the varying oxygen tension. These results suggest that the use of
      serum during IVC of embryos increases blastocyst rate without affecting the
      evaluated histone marks and that oxygen tension has an important effect on the
      histone marks H3K9me2 and H3K4me2 in bovine blastocysts.

PMID- 25777078
TI  - Chromium isotopic fractionation during Cr(VI) reduction by Bacillus sp. under
      aerobic conditions.
AB  - This study investigated the fractionation of chromium isotopes during chromium
      reduction by Bacillus sp. under aerobic condition, variable carbon source
      (glucose) concentration (0, 0.1, 1, 2.5 and 10mM), and incubation temperatures
      (4, 15, 25 and 37 degrees C). The results revealed that the delta(53)Cr values in
      the residual Cr(VI) increased with the degree of Cr reduction, and followed a
      Rayleigh fractionation model. The addition of glucose only slightly affected cell
      specific Cr(VI) reduction rates (cSRR). However, the value of epsilon (2.00+/
      0.210/00) in the experiments with different concentrations of glucose (0.1, 1,
      2.5 and 10mM) was smaller than that from the experiment without glucose (3.74+/
      0.160/00). The results indicated that the cell-specific reduction rate is not the
      sole control on the degree of isotopic fractionation, and different metabolic
      pathways would result in differing degrees of Cr isotopic fractionation. The cSRR
      decreased with decreasing temperature, showing that the values of epsilon were
      7.62+/-0.360/00, 4.59+/-0.280/00, 3.09+/-0.160/00 and 1.99+/-0.230/00 at
      temperatures of 4, 15, 25 and 37 degrees C, respectively. It shown that
      increasing cSRR linked to decreasing fractionations has been associated with
      increasing temperatures. Overall, our results revealed that temperature is a
      primary factor affecting Cr isotopic fractionation under microbial actions.

PMID- 25777079
TI  - Harmonizing and supporting infection control training in Europe.
AB  - Healthcare-associated infection (HCAI), patient safety, and the harmonization of
      related policies and programmes are the focus of increasing attention and
      activity in Europe. Infection control training for healthcare workers (HCWs) is a
      cornerstone of all patient safety and HCAI prevention and control programmes. In
      2009 the European Centre for Disease Prevention and Control (ECDC) commissioned
      an assessment of needs for training in infection control in Europe (TRICE), which
      showed a substantial increase in commitment to HCAI prevention. On the other
      hand, it also identified obstacles to the harmonization and promotion of training
      in infection control and hospital hygiene (IC/HH), mostly due to differences
      between countries in: (i) the required qualifications of HCWs, particularly
      nurses; (ii) the available resources; and (iii) the sustainability of IC/HH
      programmes. In 2013, ECDC published core competencies for infection control and
      hospital hygiene professionals in the European Union and a new project was
      launched ['Implementation of a training strategy for infection control in the
      European Union' (TRICE-IS)] that aimed to: define an agreed methodology and
      standards for the evaluation of IC/HH courses and training programmes; develop a
      flexible IC/HH taxonomy; and implement an easily accessible web tool in 'Wiki'
      format for IC/HH professionals. This paper reviews several aspects of the TRICE
      and the TRICE-IS projects. 

PMID- 25777080
TI  - A physiological, biochemical and proteomic characterization of Saccharomyces
      cerevisiae trk1,2 transport mutants grown under limiting potassium conditions.
AB  - Saccharomyces cerevisiae mutants lacking both isoforms of the main plasma
      membrane potassium transporter display impaired potassium transport and defective
      growth at limiting concentrations of the cation. Moreover, they are
      hyperpolarized and have a lower intracellular pH than wild-type. In order to
      unravel global physiological processes altered in trk1,2 mutants, we have
      established conditions at which both wild-type and mutants can grow at different
      rates. Using a combination of physiological, biochemical and proteomic
      approaches, we show that during growth at suboptimal potassium concentrations,
      double trk1,2 mutants accumulate less potassium and reach lower yields. In
      contrast, the mutants maintain increased viability in the stationary phase and
      retain more potassium. Moreover, the mutants show increased expression of stress
      related proteins such as catalase T, thioredoxin peroxidase or hexokinase 2,
      suggesting that they are better adapted to the additional stress factors
      associated with entry into stationary growth phase. 

PMID- 25777081
TI  - Nutrient transport into germinating Trichoderma atroviride conidia and
      development of its driving force.
AB  - The exit from dormancy and the start of growth should be preceded or at least
      accompanied by the uptake of nutrients. In this work we studied changes in the
      transport of several nutrients into Trichoderma atroviride conidia. Germination
      started with a short period of isodiametric growth (conidial swelling), followed
      by polarized growth (germ tube formation) after about 8 h at 26  degrees C. The
      onset of isodiametric growth required the presence of external both phosphate and
      nitrate. At the same time, an increased uptake of precursors of macromolecules
      and phospholipids ((14)C- or (3)H-labelled valine, uracil, N-acetylglucosamine
      and choline) occurred. A low uptake of these precursors was observed also in non
      germinating conidia. Concomitantly, this uptake developed an increased
      sensitivity to the uncoupler 3,3',4',5-tetrachlorosalicylanilide. Expression and
      activity of H(+)-ATPase started after completing isodiametric growth, suggesting
      that the proton-motive force (PMF) generated by H(+)-ATPase may be an accelerator
      of nutrient uptake and metabolism. (14)C-valine uptake was also measured into a
      mutant with disrupted pma1 gene. This mutant did not form conidia. The mutant
      also exhibited uncoupler sensitivity of (14)C-valine uptake. These observations
      showed that a PMF must have been generated by a mechanism(s) other than the H(+)
      ATPase activity in the WT before H(+)-ATPase expression and in mycelia with
      disrupted H(+)-ATPase.

PMID- 25777082
TI  - Environment-induced lentigines: formation of solar lentigines beyond ultraviolet
      radiation.
AB  - There is no doubt that ultraviolet radiation (UVR) contributes to the generation
      of acquired lentigines in human skin, as indicated by the term solar lentigo. A
      growing number of recent epidemiological and mechanistic studies, however,
      strongly suggest that in addition to UVR, other environmental factors contribute
      to lentigines' formation as well. We therefore here introduce the term
      'environment-induced lentigo' (EIL) to refer to acquired pigment spots of human
      skin. In this view point, we (i) summarize the existing evidence to support a
      role of environmental toxicants other than UVR in the pathogenesis of EILs, (ii)
      we argue that activation of aryl hydrocarbon receptor (AHR) signalling by UVR and
      environmental toxicants is critically involved in triggering and sustaining a
      crosstalk between melanocytes, keratinocytes and fibroblasts, which then causes
      the development and persistence of EILs in human skin, and (iii) we discuss
      clinical implications for the prevention and treatment of EILs resulting from
      this concept. 

PMID- 25777083
TI  - A suture-based liver retraction method for laparoscopic bariatric procedures:
      results from a large case series.
AB  - BACKGROUND: Laparoscopic bariatric surgery requires retraction of the left lobe
      of the liver to provide adequate operative view and working space. Conventional
      approaches utilize a mechanical retractor and require additional incision(s), and
      at times an assistant. OBJECTIVES: This study evaluated the safety and efficacy
      of a suture-based method of liver retraction in a large series of patients
      undergoing laparoscopic bariatric surgery. This method eliminates the need for a
      subxiphoid incision for mechanical retraction of the liver. SETTING: Two
      hospitals in the Midwest with a high volume of laparoscopic bariatric cases.
      METHODS: Retrospective chart review identified all patients undergoing bariatric
      surgery for whom suture-based liver retraction was selected. The left lobe of the
      liver is lifted, and sutures are placed across the right crus of the diaphragm
      and were either anchored on the abdominal wall or intraperitoneally to provide
      static retraction of the left lobe of the liver. RESULTS: In all, 487 cases were
      identified. Patients had a high rate of morbid obesity (83% with body mass index
      >40 kg/m(2)) and diabetes (34.3%). The most common bariatric procedures were Roux
      en-Y gastric banding (39%) and sleeve gastrectomy (24.6%). Overall, 6 injuries to
      the liver were noted, only 2 of which were related to the suture-based retraction
      technique. Both injuries involved minor bleeding and were successfully managed
      during the procedure. The mean number of incisions required was 4.6. CONCLUSIONS:
      Suture-based liver retraction was found to be safe and effective in this large
      case series of morbidly obese patients. The rate of complications involving the
      technique was extremely low (.4%).

PMID- 25777084
TI  - Structurally-diverse, PPARgamma-activating environmental toxicants induce
      adipogenesis and suppress osteogenesis in bone marrow mesenchymal stromal cells.
AB  - Environmental obesogens are a newly recognized category of endocrine disrupting
      chemicals that have been implicated in contributing to the rising rates of
      obesity in the United States. While obesity is typically regarded as an increase
      in visceral fat, adipocyte accumulation in the bone has been linked to increased
      fracture risk, lower bone density, and osteoporosis. Exposure to environmental
      toxicants that activate peroxisome proliferator activated receptor gamma
      (PPARgamma), a critical regulator of the balance of differentiation between
      adipogenesis and osteogenesis, may contribute to the increasing prevalence of
      osteoporosis. However, induction of adipogenesis and suppression of osteogenesis
      are separable activities of PPARgamma, and ligands may selectively alter these
      activities. It currently is unknown whether suppression of osteogenesis is a
      common toxic endpoint of environmental PPARgamma ligands. Using a primary mouse
      bone marrow culture model, we tested the hypothesis that environmental toxicants
      acting as PPARgamma agonists divert the differentiation pathway of bone marrow
      derived multipotent mesenchymal stromal cells towards adipogenesis and away from
      osteogenesis. The toxicants tested included the organotins tributyltin and
      triphenyltin, a ubiquitous phthalate metabolite (mono-(2-ethylhexyl) phthalate,
      MEHP), and two brominated flame retardants (tetrabromobisphenol-a, TBBPA, and
      mono-(2-ethylhexyl) tetrabromophthalate, METBP). All of the compounds activated
      PPARgamma1 and 2. All compounds increased adipogenesis (lipid accumulation, Fabp4
      expression) and suppressed osteogenesis (alkaline phosphatase activity, Osx
      expression) in mouse primary bone marrow cultures, but with different potencies
      and efficacies. Despite structural dissimilarities, there was a strong negative
      correlation between efficacies to induce adipogenesis and suppress osteogenesis,
      with the organotins being distinct in their exceptional ability to suppress
      osteogenesis. As human exposure to a mixture of toxicants is likely, albeit at
      low doses, the fact that multiple toxicants are capable of suppressing bone
      formation supports the hypothesis that environmental PPARgamma ligands represent
      an emerging threat to human bone health.

PMID- 25777086
TI  - Factors Implicated for Delay of Adjuvant Chemotherapy in Colorectal Cancer: A
      Meta-analysis of Observational Studies.
AB  - BACKGROUND: The survival benefit of administering adjuvant chemotherapy (AC) in
      colorectal cancer is well established, as is the impact of its timing. Although
      various factors have been associated with treatment delay, their implications
      remain controversial. We determined clinicopathological factors associated with
      delay in transition to AC via systematic review and meta-analysis. METHODS:
      Studies assessing factors for delay in initiating AC were identified from
      MEDLINE, EMBASE, and Cochrane Databases. Studies were included only if relevant
      clinicopathological factors were adequately described and appropriate comparative
      groups were balanced. For each study, the odds ratio (OR) and 95 % confidence
      interval (CI) were estimated, regarding response to early versus delayed AC
      initiation. RESULTS: We identified 15 eligible studies involving 67,537 patients.
      Twelve studies were multicentre studies and three were single-center cohort
      studies. Meta-analysis demonstrated age >75 years [4 studies, OR = 1.44 (95 % CI
      1.32-1.58)], marital status-single [3 studies, OR = 1.32 (95 % CI 1.20-1.44)],
      low socioeconomic status (SES) [7 studies, OR = 1.67 (95 % CI 1.32-2.12)], worse
      comorbidity status [5 studies, OR = 1.47 (95 % CI 1.14-1.90)], low tumour grade
      [7 studies, OR = 1.06 (95 % CI 1.02-1.11)], prolonged length of stay [3 studies,
      OR 2.37 (95 % CI 2.10-2.68)], and readmission [3 studies, OR = 3.23 (95 % CI 1.66
      6.26)] were significant predictors of delayed initiation of AC. Laparoscopy
      compared to an open surgical approach was a significant predictor of earlier AC
      initiation [5 studies, OR = 0.70 (95 % CI 0.51-0.97)]. CONCLUSIONS: Laparoscopy
      is associated with earlier initiation of AC, encouraging its increased adoption.
      Social isolation and low SES merit consideration of approaches that counter the
      lack of social support and deprivation to improve cancer outcomes.

PMID- 25777085
TI  - The Role of Sentinel Lymph Node Biopsy and Factors Associated with Invasion in
      Extensive DCIS of the Breast Treated by Mastectomy: The Cinnamome Prospective
      Multicenter Study.
AB  - BACKGROUND: When invasive components are discovered at mastectomy for vacuum
      assisted biopsy (VAB)-diagnosed ductal carcinoma in situ (DCIS), the only option
      available is axillary lymph node dissection (ALND). The primary aim of this
      prospective multicenter trial was to determine the benefit of performing upfront
      sentinel lymph node (SLN) biopsy for these patients. The secondary aim was to
      determine DCIS factors associated with microinvasion or invasion. METHODS: The
      SLN procedure was performed during mastectomy, and for positive SLN an ALND was
      performed during the same intervention. A tissue microarray containing DCIS
      lesions from the mastectomy specimens was subsequently performed. RESULTS: From
      May 2008 to December 2010, 228 patients were enrolled from 14 French cancer
      centers, including 192 eligible patients with pure DCIS on VAB and successful SLN
      procedures. ALND was avoided for 51 [67 %; 95 % confidence interval (CI), 56-77
      %] of all the patients who had microinvasive DCIS or DCIS associated with
      invasive carcinoma at mastectomy and a negative SLN. Of the 192 patients, 76 (39
      %) with VAB-diagnosed DCIS were upgraded after mastectomy to micro (n = 20) or
      invasive disease (n = 56). The rate of positive SLN for patients with DCIS on VAB
      was 14 %. High nuclear grade of DCIS was associated with greater risk of
      microinvasion and invasion, and HER2-amplified DCIS was associated with greater
      risk of invasion. CONCLUSIONS: Underestimation of invasive components is high
      when DCIS is diagnosed by VAB in patients undergoing mastectomy. Upfront SLN for
      patients with VAB-diagnosed extensive DCIS avoids unnecessary ALND for two-thirds
      of patients with micro or invasive disease on mastectomy.

PMID- 25777087
TI  - Circulating Tumor Cells as an Independent Predictor of Survival in Advanced
      Gastric Cancer.
AB  - BACKGROUND: When the indication for surgery of highly advanced gastric cancer is
      considered, careful selection of the patients is important. In addition to tumor
      node-metastasis factors and peritoneal lavage cytology (CY), which are important
      predictors of prognosis, detection of circulating tumor cells (CTCs) could be
      another potential marker. METHODS: This study prospectively evaluated CTCs using
      a semi-automated immunomagnetic separation system (CellSearch) for 136 patients
      with advanced gastric cancer to determine the frequency of CTC positivity. For
      123 patients who also had their CY evaluated, the significance of both CTC and
      CY, was investigated as a potential biomarker to predict progression-free
      survival (PFS) or to monitor the therapeutic effect. RESULTS: In 25 patients
      (18.4 %), CTCs were positive. Positive CTC counts were more common for tumors
      with diffuse histologic type and distant metastasis. The PFS of CTC-positive
      patients was significantly shorter than that of CTC-negative patients (hazard
      ratio 2.03; P = 0.016). A multivariate analysis of 123 patients showed that CTC
      and CY as well as performance status and macroscopic distant metastasis were
      independent factors for PFS. When both CTC and CY were converted to negative
      values by therapeutic interventions, long-term PFS was achieved. CONCLUSIONS:
      Detection of CTCs was an independent predictor of a shorter PFS in advanced
      gastric cancer. For selecting patients who require intensive treatment, CTCs
      could be a valuable biomarker. The combined status of CTC and CY would be useful
      in selecting patients for radical surgery. Further investigation with a larger
      number of patients is necessary to establish the importance of CTCs.

PMID- 25777088
TI  - The Supporting Role of (18)FDG-PET in Patients with Neuroendocrine Tumors.

PMID- 25777089
TI  - Evaluation of the Time-Varying Effect of Prognostic Factors on Survival in
      Ovarian Cancer.
AB  - PURPOSE: To explore the risk factors in ovarian cancer with respects of time
      varying effects on recurrence and survival. METHODS: Two hundred and ninety-eight
      patients with epithelial ovarian cancer in the Kaohsiung Veterans' General
      Hospital from January 1995 to the end of 2011 were included in the study. The
      assumption of the Cox proportional hazard model, i.e., the hazard ratio is a
      constant with time, was tested for available prognostic factors. An extended Cox
      model was then applied, and a statistical package was constructed to perform
      multivariate analysis in presence of both time-varying and time-independent
      factors. RESULTS: Most prognostic factors met the assumption of the Cox
      proportional hazard model (p > 0.05) except for cancer-associated antigen (CA)
      125 nadir concentration during first-line chemotherapy (p = 0.02). Multivariate
      analysis, where CA125 nadir was allowed to change with time while other factors
      remained constant, showed that International Federation of Gynecology and
      Obstetrics (FIGO) stage, residual tumor, CA125 nadir, and age were independent
      risk factors for recurrence and death. CONCLUSIONS: The effect of CA125 nadir on
      recurrence and overall survival is not constant over time. It loses predictivity
      on recurrence and survival after 4.5 years. Awareness of the time-varying effects
      of the prognostic factors is beneficial to gynecologists in patient consultation
      and case evaluation.

PMID- 25777090
TI  - Influence of Food Intake on the Healing Process of Postoperative Pancreatic
      Fistula After Pancreatoduodenectomy: A Multi-institutional Randomized Controlled
      Trial.
AB  - BACKGROUND: The usefulness of enteral nutrition via a nasointestinal tube for
      patients who develop postoperative pancreatic fistula (POPF) after miscellaneous
      pancreatectomy procedures has been reported. However, no clear evidence regarding
      whether oral intake is possible during management of POPF after
      pancreatoduodenectomy (PD) is currently available. We investigated the effects of
      oral food intake on the healing process of POPF after PD by a multi-institutional
      randomized controlled trial. METHODS: Patients who developed POPF were randomly
      assigned to the dietary intake (DI) group (n = 30) or the fasted group [no
      dietary intake (NDI) group] (n = 29). The primary endpoint was the length of
      drain placement. RESULTS: No significant differences were found in the length of
      drain placement between the DI and NDI groups [27 (7-80) vs. 26 (7-70) days,
      respectively; p = .8858]. POPF progressed to a clinically relevant status (grade
      B/C) in 20 patients in the DI group and 19 patients in the NDI group (p = .9257).
      POPF-related intra-abdominal hemorrhage was found in 2 patients in the NDI group,
      but in no patients in the DI group (p = .1434). There were no significant
      differences in POPF-related intra-abdominal hemorrhage, the incidence of other
      complications, or the length of the postoperative hospital stay between the 2
      groups. CONCLUSION: Food intake did not aggravate POPF and did not prolong the
      length of drain placement or hospital stay after PD. There may be no need to
      avoid oral dietary intake in patients with POPF.

PMID- 25777091
TI  - Immunohistochemical Evaluation of Minichromosome Maintenance Protein 7 (MCM7),
      Topoisomerase IIalpha, and Ki-67 in Diffuse Malignant Peritoneal Mesothelioma
      Patients Using Tissue Microarray.
AB  - PURPOSE: Immunohistochemistry and tissue microarray (TMA) were used to perform a
      prognostic analysis of markers related to cell proliferation in diffuse malignant
      peritoneal mesothelioma (DMPM). METHODS: Clinicopathologic data were extracted
      from a prospectively collected database containing cases of peritoneal
      mesothelioma treated with cytoreductive surgery and hyperthermic intraperitoneal
      chemotherapy in the National Cancer Institute of Milan from 1995 to 2013. Eighty
      one DMPM patients were recruited and their tissue samples were used to construct
      TMAs. We evaluated the immunoexpressions of markers related to cell proliferation
      topoisomerase IIalpha, minichromosome maintenance protein 7 (MCM7), and Ki-67-and
      then conducted a multivariate Cox model to identify the predictors of overall
      survival (OS) and progression-free survival (PFS) among the following parameters:
      age, sex, Eastern Cooperative Oncology Group (ECOG) performance status, baseline
      serum albumin, Charlson Comorbidity Index, previous systemic chemotherapy,
      histological subtype (epithelioid vs. biphasic/sarcomatoid), peritoneal cancer
      index, completeness of cytoreduction (CC), and proliferative biological markers.
      RESULTS: The rates of high/intermediate immunoreactivity were 95 % for
      topoisomerase IIalpha and 90 % for MCM7, and the median Ki-67 labeling index was
      5 %. The independent predictors of OS were baseline serum albumin >3.5 g/dl, CC,
      and Ki-67 >5 %, whereas those for PFS were an ECOG performance status of 0,
      baseline serum albumin >3.5 g/dl, Charlson Comorbidity Index >3, previous
      systemic chemotherapy, morbidity G3-5, and Ki-67 >5 %. The remaining biological
      markers were not associated with outcome. CONCLUSIONS: Ki-67 was found to be a
      new powerful determinant of outcome. Patients with a Ki-67 labeling index >5 %
      carry a very poor prognosis and do not benefit from the combined procedure.
      Further studies should be conducted to confirm the present data.

PMID- 25777092
TI  - Chemotherapy for Surgically Resected Intrahepatic Cholangiocarcinoma.
AB  - BACKGROUND: The benefit of chemotherapy for surgically resected intrahepatic
      cholangiocarcinoma (ICC) remains poorly defined. The present study sought to
      determine the survival impact of chemotherapy for surgically resected ICC.
      METHODS: Patients with non-metastatic ICC who underwent surgery were identified
      from the National Cancer Database (1998-2011) and stratified by receipt of
      chemotherapy. Survival outcomes were analyzed following propensity score modeling
      using the greedy matching algorithm. RESULTS: A total of 2751 patients were
      identified (median age 64 years); 985 (35.8 %) received chemotherapy. Younger
      age, advanced tumor stage, R1/R2 surgical margins, and lymph node metastasis were
      all independently associated with receipt of chemotherapy (p < 0.05). Following
      propensity score matching, advanced tumor stage, lymph node metastasis, poorly
      differentiated tumors, and R1/R2 surgical margins were associated with poorer
      overall survival (OS) (p < 0.05). Median OS comparing patients who received
      chemotherapy compared with surgery alone was 23 versus 20 months (p = 0.09).
      However, when stratified by lymph node status, chemotherapy demonstrated a
      significant improvement in median OS among N1 patients (19.8 vs. 10.7 months; p <
      0.001). In contrast, patients with N0 disease derived no benefit from
      chemotherapy (29.4 vs. 29 months; p = 0.33). Additional tumor characteristics
      associated with improved survival with chemotherapy included T3/T4 tumors (21.3
      vs. 15.6 months; p < 0.001) and R1/R2 surgical margins (19.5 vs. 11.6 months; p =
      0.006). CONCLUSION: The use of chemotherapy was associated with a survival
      benefit only for ICC patients with nodal metastasis, advanced tumor stage, or an
      inadequate surgical resection. Chemotherapy for resected ICC should be strongly
      considered for tumors harboring high-risk features.

PMID- 25777093
TI  - Do MRI and mammography reliably identify candidates for breast conservation after
      neoadjuvant chemotherapy?
AB  - BACKGROUND: Neoadjuvant chemotherapy (NAC) may allow breast-conserving therapy
      (BCT) in patients who require mastectomy at presentation. Breast MRI is more
      accurate than mammography in assessing treatment response, but combined test
      reliability in identifying BCT candidates after NAC is not well described. We
      evaluated whether post-NAC breast MRI alone and with mammography accurately
      identifies BCT candidates. METHODS: In this retrospective study of 111
      consecutive breast cancer patients receiving NAC, all had pre- and
      postchemotherapy MRI, followed by surgery. Posttreatment MRI and mammography
      results were correlated with surgical outcomes and pathologic response. RESULTS:
      Fifty-one of 111 (46 %) patients presented with multicentric or inflammatory
      breast cancer and were not BCT candidates. The remaining 60 (54 %) were
      considered BCT candidates after downstaging (mean age: 47 years). All 60 had at
      least a partial response to NAC and were suitable for BCT on MRI after NAC. Forty
      five of 60 (75 %) underwent lumpectomy; 15 of 60 (25 %) chose mastectomy. Forty
      one of 45 (91 %) of lumpectomies were successful; 4 of 45 (9 %) required
      mastectomy. Twelve of 15 (80 %) patients choosing mastectomy could have undergone
      BCT based on pathology; 3 of 15 (20 %) did require mastectomy. Two of these three
      patients had extensive microcalcifications on mammogram, indicating the need for
      mastectomy despite MRI suitability for BCS. MRI alone correctly predicted BCS in
      53 of 60 (88 %) patients. MRI plus mammography was correct in 55 of 60 (92 %),
      although only 9 of 45 (20 %) BCT patients and 4 of 15 (27 %) potentially
      conservable mastectomy patients had complete pathologic responses. CONCLUSIONS:
      Posttreatment MRI plus mammography is an accurate method to determine whether BCT
      is possible after NAC is given to downstage disease.

PMID- 25777094
TI  - Implications of HER2-targeted therapy on extent of surgery for early-stage breast
      cancer.

PMID- 25777095
TI  - Surgical Treatment of Recurrent Endometrial Cancer: Time for a Paradigm Shift.
AB  - BACKGROUND: Although surgery represents the cornerstone treatment of endometrial
      cancer at initial diagnosis, scarce data are available in recurrent setting. The
      purpose of this study was to review the outcome of surgery in these patients.
      METHODS: Medical records of all patients undergoing surgery for recurrent
      endometrial cancer at NCI Milano between January 2003 and January 2014 were
      reviewed. Survival was determined from the time of surgery for recurrence to last
      follow-up. Survival was estimated using Kaplan-Meier methods. Differences in
      survival were analyzed using the log-rank test. The Fisher's exact test was used
      to compare optimal versus suboptimal cytoreduction against possible predictive
      factors. RESULTS: Sixty-four patients were identified. Median age was 66 years.
      Recurrences were multiple in 38 % of the cases. Optimal cytoreduction was
      achieved in 65.6 %. Median OR time was 165 min, median postoperative hemoglobin
      drop was 2.4 g/dl, and median length hospital stay was 5.5 days. Eleven patients
      developed postoperative complications, but only four required surgical
      management. Estimated 5-year progression-free survival (PFS) was 42 and 19 % in
      optimally and suboptimally cytoreduced patients, respectively. At multivariate
      analysis, only residual disease was associated with PFS. Estimated 5-year overall
      survival (OS) was 60 and 30 % in optimally and suboptimally cytoreduced patients,
      respectively. At multivariate analysis, residual disease and histotype were
      associated with OS. At multivariate analysis, only performance status was
      associated with optimal cytoreduction. CONCLUSIONS: Secondary cytoreduction in
      endometrial cancer is associated with long PFS and OS. The only factors
      associated with improved long-term outcome are the absence of residual disease at
      the end of surgical resection and histotype.

PMID- 25777096
TI  - Outcomes of Modified Harrington Reconstructions for Nonprimary Periacetabular
      Tumors: An Effective and Inexpensive Technique.
AB  - BACKGROUND: Metastatic disease to the acetabulum presents a difficult technical
      and philosophical challenge: complicated surgeries in patients with often short
      life expectancies force us to examine both the outcome and cost of these
      operations. Therefore, we studied the durability of a cement-screw rebar
      reconstruction technique and risk factors for failure, and we compare the results
      to other reconstruction options. METHODS: This is a retrospective review of 52
      acetabular reconstructions in 50 patients for nonprimary disease using a
      retrograde screw-rebar-cement all-polyethylene technique. Mean age was 57 years
      (range 25-81 years). Twenty-four lesions were classified as Harrington class II;
      28 were Harrington class III. Mean follow-up was 17.7 months (range 1-92 months).
      Outcomes included patient survival, prosthesis survival, and complications.
      RESULTS: Forty-eight of 50 (96 %) patients ambulated after surgery. Five of 52
      (9.6 %) of prostheses failed, three from loosening due to tumor progression, one
      from aseptic loosening, and one from soft tissue instability (dislocation). The
      three cases of tumor progression failure occurred in patients with massive
      preoperative ischial tumor burden. Mean surgical time was 198 min, and hospital
      stay was 5.2 days. DISCUSSION: The screw-cement-rebar all-polyethylene cup
      reconstruction technique is a comparatively successful and inexpensive
      reconstruction option for treating nonprimary oncologic disease in the
      acetabulum. All cases of loosening occurred beyond the median patient survival.
      Surgeons should be wary of massive ischial tumor burden in patients with
      projected longevity, as it may be associated with implant failure. Surgical time
      and hospital stay are consistent with historical data for alternative implants,
      and implant cost is lower.

PMID- 25777130
TI  - [On the problematic of assessment of complex posttraumatic stress disorder].

PMID- 25777131
TI  - [Patient access to medical records. Ethical considerations on its realization in
      psychiatry].
AB  - BACKGROUND: In medical ethics there is broad agreement that patients should be
      empowered to make autonomous decisions about their health and that objective,
      detailed information promotes these decisions. According to German law patients
      have a right of access to their own medical records. OBJECTIVES: Which advantages
      and disadvantages does the access to records have for doctors and patients in
      psychiatry? Which requirements should be met to make access reasonable for
      patients? MATERIAL AND METHODS: This article presents an analysis of the legal
      situation and the state of research, evaluation of empirical studies, discussion
      of features of psychiatry, its language and patients as well as their influence
      on access to medical records. RESULTS: Psychiatrists are sometimes concerned
      about patient access to medical records and some psychiatric patients feel upset
      or uncomfortable after having inspected their records. The misunderstanding and
      stigmatization of psychiatric terms, the vulnerability of psychiatric patients
      and the nature of psychiatric disorders, the description of which affects
      fundamental aspects of personality, all play a role in this. In addition, in
      having access to their records patients use a source of information that was
      originally written for other addressees. Information content and language are not
      adapted to their needs. Possible solutions could involve improvements in patient
      education and (stylistic) changes in writing records.

PMID- 25777132
TI  - [Psychiatric manifestations of primary Sjogren's syndrome].

PMID- 25777133
TI  - [Diverse seizures, unusual EEG seizure pattern and episodic organic brain
      syndrome. A case report].

PMID- 25777134
TI  - Engineering Bacillus subtilis for the conversion of the antimetabolite 4-hydroxy
      l-threonine to pyridoxine.
AB  - Until now, pyridoxine (PN), the most commonly supplemented B6 vitamer for animals
      and humans, is chemically synthesized for commercial purposes. Thus, the
      development of a microbial fermentation process is of great interest for the
      biotech industry. Recently, we constructed a Bacillus subtilis strain that formed
      significant amounts of PN via a non-native deoxyxylulose 5'-phosphate-(DXP)
      dependent vitamin B6 pathway. Here we report the optimization of the condensing
      reaction of this pathway that consists of the 4-hydroxy-l-threonine-phosphate
      dehydrogenase PdxA, the pyridoxine 5'-phosphate synthase PdxJ and the native DXP
      synthase, Dxs. To allow feeding of high amounts of 4-hydroxy-threonine (4-HO-Thr)
      that can be converted to PN by B. subtilis overexpressing PdxA and PdxJ, we first
      adapted the bacteria to tolerate the antimetabolite 4-HO-Thr. The adapted
      bacteria produced 28-34mg/l PN from 4-HO-Thr while the wild-type parent produced
      only 12mg/l PN. Moreover, by expressing different pdxA and pdxJ alleles in the
      adapted strain we identified a better combination of PdxA and PdxJ enzymes than
      reported previously, and the resulting strain produced 65mg/l PN. To further
      enhance productivity mutants were isolated that efficiently take up and convert
      deoxyxylulose (DX) to DXP, which is incorporated into PN. Although these mutants
      were very efficient to convert low amount of exogenous DX, at higher DX levels
      they performed only slightly better. The present study uncovered several enzymes
      with promiscuous activity and it revealed that host metabolic pathways compete
      with the heterologous pathway for 4-HO-Thr. Moreover, the study revealed that the
      B. subtilis genome is quite flexible with respect to adaptive mutations, a
      property, which is very important for strain engineering. 

PMID- 25777135
TI  - A carbon sink pathway increases carbon productivity in cyanobacteria.
AB  - The burning of fossil reserves, and subsequent release of carbon into the
      atmosphere is depleting the supply of carbon-based molecules used for synthetic
      materials including plastics, oils, medicines, and glues. To provide for future
      society, innovations are needed for the conversion of waste carbon (CO2) into
      organic carbon useful for materials. Chemical production directly from
      photosynthesis is a nascent technology, with great promise for capture of CO2
      using sunlight. To improve low yields, it has been proposed that photosynthetic
      capacity can be increased by a relaxation of bottlenecks inherent to growth. The
      limits of carbon partitioning away from growth within the cell and the effect of
      partitioning on carbon fixation are not well known. Here we show that expressing
      genes in a pathway between carbon fixation and pyruvate increases partitioning to
      2,3-butanediol (23BD) and leads to a 1.8-fold increase in total carbon yield in
      the cyanobacterium Synechococcus elongatus PCC 7942. Specific 2,3-butanediol
      production increases 2.4-fold. As partitioning increases beyond 30%, it leads to
      a steep decline in total carbon yield. The data suggests a local maximum for
      carbon partitioning from the Calvin Benson cycle that is scalable with light
      intensity. 

PMID- 25777136
TI  - Intramolecular decarboxylative coupling as the key step in copper-catalyzed
      domino reaction: facile access to 2-(1,3,4-oxadiazol-2-yl)aniline derivatives.
AB  - A copper-catalyzed domino protocol for the synthesis of 2-(1,3,4-oxadiazol-2
      yl)aniline derivatives has been developed from simple and available isatins and
      hydrazides. This domino process integrated consecutive condensation, base
      promoted ring-opening and the key copper-catalyzed decarboxylative coupling for
      intramolecular C-O bond formation. 

PMID- 25777137
TI  - Crossing Y-stent technique with dual open-cell stents for coiling of wide-necked
      bifurcation aneurysms.
AB  - OBJECTIVE: Double stenting in a Y-configuration is a promising therapeutic option
      for wide-necked cerebral aneurysms not amenable to reconstruction with a single
      stent. We retrospectively evaluated the efficacy and safety of the crossing Y
      stent technique for coiling of wide-necked bifurcation aneurysms. METHODS: By
      collecting clinical and radiological data we evaluated from January 2007 through
      December 2013, 20 wide-necked bifurcation aneurysms. RESULTS: Twelve unruptured
      and eight ruptured aneurysms in 20 patients were treated with crossing Y-stent
      assisted coiling. Aneurysm size and neck size ranged from 3.2 to 28.2mm (mean
      7.5mm) and from 1.9 to 9.1mm (mean 4.5mm). A Y-configuration was established
      successfully in all 20 patients. All aneurysms were treated with a pair of
      Neuroform stents. The immediate angiographic results were total occlusion in 17
      aneurysms, residual neck in two, and residual sac in one. Peri-operative
      morbidity was only 5%. Fifteen of 18 surviving patients underwent follow-up
      conventional angiography (mean, 10.9 months). The result showed stable occlusion
      in all 15 aneurysms and asymptomatic in-stent occlusion in one branch artery. At
      the end of the observation period (mean, 33.5 months), all 12 patients without
      subarachnoid hemorrhage had excellent clinical outcomes (mRS 0), except one (mRS
      2). Of eight patients with subarachnoid hemorrhage, four remained symptom free
      (mRS 0), while the other four had were dependent or dead (mRS score, 3-6).
      CONCLUSION: In this report on 20 patients, crossing Y-stent technique for coiling
      of wide-necked bifurcation aneurysms showed a good technical safety and favorable
      clinical and angiographic outcome.

PMID- 25777138
TI  - Cue generation: How learners flexibly support future retrieval.
AB  - The successful use of memory requires us to be sensitive to the cues that will be
      present during retrieval. In many situations, we have some control over the
      external cues that we will encounter. For instance, learners create shopping
      lists at home to help remember what items to later buy at the grocery store, and
      they generate computer file names to help remember the contents of those files.
      Generating cues in the service of later cognitive goals is a complex task that
      lies at the intersection of metacognition, communication, and memory. In this
      series of experiments, we investigated how and how well learners generate
      external mnemonic cues. Across 5 experiments, learners generated a cue for each
      target word in a to-be-remembered list and received these cues during a later
      cued recall test. Learners flexibly generated cues in response to different
      instructional demands and study list compositions. When generating mnemonic cues,
      as compared to descriptions of target items, learners produced cues that were
      more distinct than mere descriptions and consequently elicited greater cued
      recall performance than those descriptions. When learners were aware of competing
      targets in the study list, they generated mnemonic cues with smaller cue-to
      target associative strength but that were even more distinct. These adaptations
      led to fewer confusions among competing targets and enhanced cued recall
      performance. These results provide another example of the metacognitively
      sophisticated tactics that learners use to effectively support future retrieval. 

PMID- 25777139
TI  - Optimization of charge carrier transport balance for performance improvement of
      PDPP3T-based polymer solar cells prepared using a hot solution.
AB  - Polymer solar cells (PSCs), with poly(diketopyrrolopyrrole-terthiophene)
      (PDPP3T):[6,6]-phenyl-C71-butyric acid methyl ester (PC71BM) as the active
      layers, were fabricated using solutions of different temperatures. The best power
      conversion efficiency (PCE) of the PSCs prepared using a hot solution was about
      6.22%, which is better than 5.54% for PSCs prepared using cool (room temperature)
      solutions and 5.85% for PSCs prepared using cool solutions with a 1,8
      diiodooctane (DIO) solvent additive. The underlying reasons for the improved PCE
      of the PSCs prepared using a hot solution could be attributed to the more
      dispersive donor and acceptor distribution in the active layer, resulting in a
      better bi-continuous interpenetrating network for exciton dissociation and charge
      carrier transport. An enhanced and more balanced charge carrier transport in the
      active layer is obtained for the PSCs prepared using a hot solution, which can be
      determined from the J-V curves of the related hole-only and electron-only
      devices. 

PMID- 25777140
TI  - IQGAP1 modulates the proliferation and migration of vascular smooth muscle cells
      in response to estrogen.
AB  - Vascular smooth muscle cell (VSMC) proliferation and migration has been proven to
      be a critical event in the development of varicosity. Variations in estrogen
      levels, a pathological event related to age and pregnancy, play a role in the
      pathogenesis of varicosity. Previous studies have reported a different response
      of VSMCs following estrogen stimulation. However, the exact mechanisms involved
      have not yet been elucidated. In the present study, we examined the responses of
      lesion and normal VSMCs treated with 10(-8) M 17beta-estradiol (E2) for 24 h. A
      differential effect of exposure to E2 was observed in these cells. IQ-domain
      GTPase-activating protein 1 (IQGAP1), a scaffold protein, was overexpressed in
      the lesion VSMCs and was shown to modulate VSMC proliferation and migration in
      response to E2. Furthermore, the increased expression of IQGAP1 was found to be
      intimately associated with a high activity of estrogen receptor alpha (ERalpha),
      which has been implicated in the regulation of VSMC physiological function.
      Additionally, we found that two critical kinases, Akt and extracellular signal
      regulated kinase (ERK), mediated the activation of ERalpha and VSMC
      proliferation. According to our results, we thus concluded that high levels of
      IQGAP1 in VSMCs regulate the physiological reaction of the cells in response to
      estrogen exposure, and that kinases are involved in the process by mediating
      ERalpha activation. In view of the essential role of IQGAP1 in the physiological
      function of VSMCs, targeting this molecule may prove to be a promising strategy
      for the treatment of varicosity.

PMID- 25777141
TI  - High tobacco consumption lowers body weight: a Mendelian randomization study of
      the Copenhagen General Population Study.
AB  - BACKGROUND: Conflicting evidence has been found regarding the association between
      high tobacco consumption and body weight among smokers. We tested the hypothesis
      that high tobacco consumption is causally associated with low body weight.
      METHODS: We conducted a Mendelian randomization study with a genetic variant in
      CHRNA3 (rs1051730) as proxy for high tobacco consumption. The cohort consisted of
      80,342 participants from the Copenhagen General Population Study, with details on
      body weight, smoking habits and CHRNA3 genotype, including 15,220 current
      smokers. RESULTS: In observational analyses, high tobacco consumption was
      associated with high body weight, body mass index, waist circumference, hip
      circumference and waist-hip ratio. In multivariable adjusted models a 1
      cigarette/day higher tobacco consumption was associated with 0.05 kg (95%
      confidence interval 0.02; 0.08) higher body weight, 0.02 kg/m(2) (0.01; 0.02)
      higher body mass index, 0.10 cm (0.07; 0.12) higher waist circumference and 0.02
      cm (0.001; 0.03) higher hip circumference. In contrast, the per-allele increase
      inCHRNA3 rs1051730 associated with high tobacco consumption was associated with
      0.59 kg (0.96; 0.22) lower body weight, 0.23 kg/m(2) (0.33; 0.13) lower body mass
      index, 0.32 cm (0.74; 0.003) lower waist circumference and 0.45 cm (0.66; 0.24)
      lower hip circumference. No association was found between tobacco consumption and
      waist-hip ratio in genetic analysis, or among CHRNA3 genotype and any of the
      outcome variables in former or never smokers. CONCLUSIONS: High tobacco
      consumption causes lower body weight among current smokers. However, smoking does
      not seem to affect body shape or fat distribution causally. The lack of
      association between CHRNA3 genotype and body weight among former smokers and
      never smokers favours smoking as the causal factor for the observed associations.

PMID- 25777142
TI  - Overexpression of N-myc downstream-regulated gene 1 inhibits human glioma
      proliferation and invasion via phosphoinositide 3-kinase/AKT pathways.
AB  - N-myc downstream-regulated gene 1 (NDRG1) was previously shown to exhibit low
      expression in glioma tissue as compared with that in normal brain tissue;
      however, the role of NDRG1 in human glioma cells has remained to be elucidated.
      The present study used the U87 MG and SHG-44 human glioma cell lines as well as
      the normal human astrocyte cell line 1800, which are known to have differential
      NDRG1 expression. Small interfering (si)RNA targeting NDRG1, and NDRG1
      overexpression vectors were transfected into the SHG-44 and U87 MG glioma cells,
      respectively. Cell proliferation, invasion, apoptosis and cell cycle arrest were
      subsequently examined by MTT assay, transwell chamber assay, flow cytometry and
      western blot analysis, respectively. Furthermore, a subcutaneous tumor mouse
      model was used to investigate the effects of NDRG1 on the growth of glioma cells
      in vivo. Overexpression of NDRG1 was shown to inhibit cell proliferation and
      invasion, and induce apoptosis in the U87 MG glioma cells, whereas NDRG1
      downregulation increased proliferation, suppressed apoptosis and promoted
      invasion of the SHG-44 glioma cells. In addition, in the subcutaneous tumor mouse
      model, overexpression of NDRG1 in U-87 MG cells suppressed tumorigenicity in
      vivo. The findings of the present study indicated that NDRG1 is required for the
      inhibition of gliomagenesis; therefore, targeting NDRG1 and its downstream
      targets may represent novel therapies for the treatment of glioma.

PMID- 25777143
TI  - The association of obesity with sex hormone-binding globulin is stronger than the
      association with ageing--implications for the interpretation of total
      testosterone measurements.
AB  - OBJECTIVE: Total testosterone concentrations are influenced by sex hormone
      binding globulin (SHBG) concentrations, which are decreased by obesity and
      increased with ageing. Therefore, we sought to understand and compare the
      associations of ageing and obesity with SHBG. DESIGN: We performed a
      retrospective, cross-sectional analysis of the associations of obesity and age on
      SHBG and testosterone measurements in men being evaluated for hypogonadism.
      PATIENTS, MEASUREMENTS AND ANALYSIS: A total of 3671 men who underwent laboratory
      testing for testosterone deficiency from the Veterans Administration Puget Sound
      Health Care System from 1997 through 2007 was included. Univariate and
      multivariate linear regression modelling of the associations between age and body
      mass index (BMI) and SHBG was performed. RESULTS: Obesity was associated with a
      significantly lower SHBG [beta = -1.26 (95% CI -1.14, -1.38) nmol/l] per unit
      increase in BMI. In contrast, ageing was associated with a significantly
      increased SHBG [beta = 0.46 (95% CI 0.39, 0.53) nmol/l per year] (P < 0.001 for
      both effects). The association of obesity with lower SHBG was two to three times
      larger than the association of ageing with increased SHBG in both univariate and
      multivariate modelling. On average, obese men (BMI >30 kg/m(2)) had significantly
      lower SHBG and total testosterone concentrations than nonobese men [(mean +/- SD)
      SHBG: 36 +/- 22 vs 50 +/- 27 nmol/l and total testosterone: 10.5 +/- 5.4 nmol/l
      vs 14.1 +/- 7.4 nmol/l; (P < 0.001 for both comparisons)], but calculated free
      testosterone concentrations did not differ between obese and nonobese men.
      CONCLUSIONS: We found that the association between obesity and lowered SHBG is
      greater than the association of ageing with increased SHBG. These competing
      effects may impact total testosterone measurements for the diagnosis of low
      testosterone, particularly in obese men.

PMID- 25777144
TI  - Simple and complex disorder in binary mixtures with benzene as a common solvent.
AB  - Substituting benzene for water in computer simulations of binary mixtures allows
      one to study the various forms of disorder, without the complications often
      encountered in aqueous mixtures. In particular, we study the relationship between
      the local order generated by different types of molecular interactions and the
      nature of the global disorder, by analyzing the relationship between the
      concentration fluctuations and the correlation functions and the associated
      structure factors. Alkane-benzene mixtures are very close to ideal mixtures,
      despite appreciable short range shape mismatch interactions, acetone-benzene
      mixtures appear as a good example of regular mixtures, and ethanol-benzene
      mixtures show large micro-segregation. In the latter case, we can unambiguously
      demonstrate, unlike in the case of water, the appearance of domain-domain
      correlations, both in the correlation functions and the structure factor
      calculated in computer simulations. This finding helps to confirm the existence
      of a pre-peak in the structure factor associated with the micro-heterogeneity,
      which was speculated from several of our previous simulations of aqueous-alcohol
      mixtures. The fact that benzene as a solvent allows us to solve some of the
      problems that could not be solved with water points towards some of the
      particularities of water as a solvent, which we discuss herein. The concept of
      molecular emulsion put forward in our earlier work is useful in formulating these
      differences between water and benzene through the analogy with direct and inverse
      micellar aggregates. 

PMID- 25777145
TI  - Acquired left ventricle-to-right atrium shunt: clinical implications and
      diagnostic dilemmas.
AB  - BACKGROUND: The acquired left ventricle-to-right atrium (LV-RA) shunt (Gerbode
      defect) is rare but it can sometimes be a critical condition. The diagnosis is
      quite challenging largely due to its exotic anatomic features and diagnostic
      difficulties. This study aims to present the clinical features and diagnostic
      solutions of this rare lesion. METHODS: Data source was based on a comprehensive
      literature retrieval of acquired LV-RA shunts of 1990-2014. RESULTS: Most of the
      acquired LV-RA shunts are of either a postoperative or an infective etiology.
      Transthoracic echocardiography showed a 62.2% accurate diagnosis, 13.4% inclusive
      diagnosis, 9.8% missed diagnosis, and 14.5% misdiagnosis rate. The accurate
      diagnostic rate of transthoracic echocardiography was significantly lower than
      that of the transesophageal echocardiography or cardiac catheterization. The LV
      RA shunts are often misinterpreted as mitral regurgitation, pulmonary
      hypertension, tricuspid regurgitation, Valsalva aneurysm rupture, and
      subaortic/high perimembrane/residual ventricular septal defect. Surgical,
      interventional, and conservative treatments were applied in 57.8, 24.4, and 17.8%
      patients, respectively. Prognosis showed an event-free survival of 85%, a
      comorbidity of 9.1%, and a mortality of 13.6%. CONCLUSIONS: A high jet detected
      in the right atrium with uncertain origin and course has to appeal to additional
      diagnostic techniques including transesophageal echocardiography, cardiac
      catheterization, or cardiac magnetic resonance imaging for differential
      diagnoses. Small restrictive shunts are preferred with conservative treatments,
      high-risk patients are candidates of interventional therapy, and the patients
      with unstable hemodynamics warrant an open heart surgery. Careful operative
      maneuver, good control of intracardiac infection, preservation of heart function,
      etc., are mandatory for the prevention of the development of an acquired LV-RA
      shunt.

PMID- 25777146
TI  - Association of mean platelet volume level with in-hospital major adverse events
      in infective endocarditis.
AB  - We hypothesised that increased on-admission and follow-up mean platelet volume
      (MPV) levels would correlate with adverse outcomes in patients with infective
      endocarditis (IE). A total of 108 consecutive patients were grouped into two
      according to median MPV level (<= 8.6 and > 8.6 fL). Patients with MPV level of >
      8.6 fL had a significantly higher rate of end-stage renal disease, Staphylococcus
      aureus infection, higher CRP levels, embolic events and in-hospital mortality
      compared to patients with MPV levels <= 8.6 fL. In multivariable Cox regression
      analysis, previous history of IE, S. aureus infection, end-stage renal disease,
      depressed LVEF, early surgical intervention, vegetation size >= 10 mm, presence
      of perivalvular abscess, higher on-admission platelet count, CRP and MPV levels
      emerged as independent predictors of in-hospital unfavourable outcomes. Patients
      with embolic events and in-hospital mortality revealed an incremental trend for
      MPV levels compared to patients without any adverse events. Our study results
      suggest that both on-admission and follow-up MPV levels may be a simple and
      available biomarker for risk stratification of IE patients.

PMID- 25777147
TI  - Can the ankle brachial pressure index (ABPI) and carotis intima media thickness
      (CIMT) be new early stage markers of subclinical atherosclerosis in patients with
      rheumatoid arthritis?
AB  - BACKGROUND: It takes years for atherosclerosis to manifest symptoms. However, it
      needs to be identified earlier because of the premature cardiovascular risk
      factors in patients with rheumatoid arthritis (RA). In this study, we aimed to
      investigate the effect of atherosclerosis on the ankle brachial pressure index
      (ABPI) and carotis intima media thickness (CIMT) in patients with RA. METHODS: RA
      patients attending the rheumatology clinic were examined retrospectively; then we
      called them for the measurements of ABPI and CIMT prospectively. Subjects were
      divided into four groups, as follows (Table 1): group 1 comprised RA patients
      with an ABPI less than 0.9; group 2 included RA patients with an ABPI between 0.9
      and 1.2; group 3 was made up of RA patients with an ABPI greater than 1.2; and
      group 4 included patients without RA with an ABPI between 0.9 and 1.2 as a
      control group. Patients' demographic data were recorded. Hypertension (HT),
      diabetes mellitus, ABPI and CIMT measurements were taken by specialists. Duration
      of RA and disease scores (disease activity score-28, health assessment
      questionnaire score and visual assessment score) were recorded. RESULTS: The
      prevalence of peripheral vascular disease in patients with RA was twice as high
      as that in the normal population of equivalent age. Patients in group 2, with RA
      and normal ABPI, exhibited a significant higher mean in CIMT (mm) compared with
      the control group (p < 0.01), despite having normal ABPI. This confirms that
      these patients have a higher risk of stroke compared with the control group.
      Group 1's newly diagnosed HT (p < 0.01) and systolic blood pressure (SBP) values
      (p < 0.01) were higher and statistically significant when compared with the group
      4 (control group); in addition, significant plaque levels were observed in the
      carotid arteries (p < 0.01). Group 3 patients had a similar history of HT and
      increased SBP compared with patients in group 4 (p < 0.01), and had similar
      characteristics to with group 1. No statistically significant differences were
      found between the groups in terms of inflammatory markers such as C-reactive
      protein and rheumatoid factor, anti-cyclic citrullinated peptide and white blood
      cell counts. CONCLUSION: Based on the present findings, patients with RA need to
      be evaluated in the early stage of the disease for subclinical peripheral artery
      disease using the ABPI, as well as CIMT, which is also a non-invasive technique,
      in terms of cerebrovascular events. Inflammatory markers exhibited no
      statistically significant difference. We think that the atherosclerotic process
      stems not only from the inflammatory effects of RA, but also perhaps from its
      immunological nature.

PMID- 25777148
TI  - Achieving EQE of 16,700% in P3HT:PC71BM based photodetectors by trap-assisted
      photomultiplication.
AB  - We report a trap-assisted photomultiplication (PM) phenomenon in solution
      processed polymer photodetectors (PPDs) based on P3HT:PC71BM as the active layer,
      the maximum EQE of 16,700% is obtained for the PPDs with PC71BM doping weight
      ratio of 1%. The PM phenomenon is attributed to the enhanced hole tunneling
      injection assisted by trapped electrons in PC71BM near Al cathode, which can be
      demonstrated by the transient photocurrent curves and EQE spectra of PPDs with
      different PC71BM doping ratios. The positive effect of trapped electrons in
      PC71BM near Al cathode on the hole tunneling injection is further confirmed by
      the simulated optical field and exciton generation rate distributions in the
      active layer and the EQE spectra of PPDs with Al(1)/P3HT:PC71BM(100:1)/Al(2)
      device structure under forward and reverse biases. This discovery may open a new
      road for organic materials to be used in highly sensitive photodetectors while
      preserving the advantages of organic materials. 

PMID- 25777149
TI  - The role of plant small RNAs in NB-LRR regulation.
AB  - Small RNAs constitute a fundamental layer of gene regulation for diverse
      biological processes in plants, including development, metabolism and stress
      responses. With the advance of high-throughput sequencing technologies and the
      rapid accumulation of transcriptomic data, the scope of regulation afforded by
      small RNAs has expanded to encompass plant innate immune responses. Plants have
      evolved the capacity to control the infection through intracellular surveillance
      proteins of the nucleotide binding site-leucine-rich repeat (NB-LRR) family that
      recognize pathogen-encoded effectors and initiate effector-triggered immunity.
      Emerging evidence indicates that plants have evolved to use specific microRNAs
      that target conserved domains of NB-LRR-encoding genes and trigger the production
      of a phased array of 21-nucleotide secondary small interfering RNAs to amplify
      the silencing effect. Herein, this review describes recent advances in
      understanding the roles of small RNAs in NB-LRR regulation that provide new
      insights into small RNA-mediated arms race between plants and their pathogens and
      discuss the unresolved questions and the future prospects for research on this
      topic. 

PMID- 25777150
TI  - Post-transplantation diabetes mellitus: evaluation of treatment strategies.
AB  - BACKGROUND: Post-transplantation diabetes mellitus (PTDM) is a serious
      complication after kidney transplantation, but evidence regarding long-term
      outcomes of treatment regimens remains scarce. AIM AND METHODS: The aim of this
      retrospective cohort analysis was to assess the long-term efficiency and safety
      of antidiabetic treatments in kidney transplant recipients (KTRs), who were
      diagnosed with PTDM by an oral glucose tolerance test (OGTT). RESULTS: Of 561
      KTRs that were screened for PTDM at our outpatient clinic, 71 (13%) had a
      diabetic OGTT and were included in this study. Mean follow-up was 34.2 +/- 16.1
      months. Thirty-six PTDM patients (51%) received antidiabetic treatment after
      diagnosis with either a dipeptidyl peptidase-4 (DPP-4) inhibitor, a sulfonylurea,
      pioglitazone, or insulin. These patients had significantly higher fasting glucose
      and two-h plasma glucose (2HPG) values at baseline than those who remained
      without therapy. In contrast to lifestyle modification alone or sulfonylureas,
      DPP-4 inhibitors improved glycemic control significantly. Adverse events were
      generally mild and occurred at similar rates in all groups. CONCLUSION: While
      sulfonylureas failed to improve glycemic control, DPP-4 inhibitors appeared
      effective and safe for the therapy of PTDM after kidney transplantation.

PMID- 25777151
TI  - A morphological novelty for feeding and sound production in the yellowtail
      clownfish.
AB  - The yellowtail clownfish Amphiprion clarkii is able to close its mouth very
      quickly by means of the cerato-mandibular (c-md) ligament, a synapomorphic trait
      of Pomacentridae joining the hyoid bar to the medial part of the lower jaw. This
      fast closure induces tooth collision, thus producing sounds that the clownfish
      uses during agonistic behaviors. To investigate whether this rapid jaw movement
      is also used during feeding, we analyzed the kinematics of sound production and
      feeding. Sound production, feeding on live planktonic prey, and feeding on food
      attached to tweezers was filmed with a high-speed camera. Three kinds of
      kinematic patterns were detected and were associated with the two different types
      of food presented: one performed to catch planktonic prey (PP), and two (called B
      1 and B-2) to bite attached food items. The kinematic pattern of B-2 is similar
      to that observed during sound production (SP) and the transection of the c-md
      ligament highlights that sound production and biting-2 motions are dependent on
      this morphological trait. Our data show that the c-md ligament in addition to its
      role in sound production allows duplication of the mouth-closing mechanism during
      feeding. This highlights the key role played by the c-md ligament in sound
      production and feeding on attached prey. J. Exp. Zool. 323A: 227-238, 2015. (c)
      2015 Wiley Periodicals, Inc. 

PMID- 25777152
TI  - New clues regarding the mysterious mechanism of activated thrombin-activatable
      fibrinolysis inhibitor self-destruction.

PMID- 25777153
TI  - A Promiscuous De Novo Retro-Aldolase Catalyzes Asymmetric Michael Additions via
      Schiff Base Intermediates.
AB  - Recent advances in computational design have enabled the development of primitive
      enzymes for a range of mechanistically distinct reactions. Here we show that the
      rudimentary active sites of these catalysts can give rise to useful chemical
      promiscuity. Specifically, RA95.5-8, designed and evolved as a retro-aldolase,
      also promotes asymmetric Michael additions of carbanions to unsaturated ketones
      with high rates and selectivities. The reactions proceed by amine catalysis, as
      indicated by mutagenesis and X-ray data. The inherent flexibility and tunability
      of this catalyst should make it a versatile platform for further optimization
      and/or mechanistic diversification by directed evolution. 

PMID- 25777154
TI  - Monitoring the folding kinetics of a beta-hairpin by time-resolved IR
      spectroscopy in silico.
AB  - Protein folding is one of the most fundamental problems in modern biochemistry.
      Time-resolved infrared (IR) spectroscopy in the amide I region is commonly used
      to monitor folding kinetics. However, associated atomic detail information on the
      folding mechanism requires simulations. In atomistic simulations structural order
      parameters are typically used to follow the folding process along the simulated
      trajectories. However, a rigorous test of the reliability of the mechanisms found
      in the simulations requires calculation of the time-dependent experimental
      observable, i.e., in the present case the IR signal in the amide I region. Here,
      we combine molecular dynamics simulation with a mixed quantum mechanics/molecular
      mechanics theoretical methodology, the Perturbed Matrix Method, in order to
      characterize the folding of a beta-hairpin peptide, through modeling the time
      dependence of the amide I IR signal. The kinetic and thermodynamic data (folding
      and unfolding rate constants, and equilibrium folded- and unfolded-state
      probabilities) obtained from the fit of the calculated signal are in good
      agreement with the available experimental data [Xu et al. J. Am. Chem. Soc. 2003,
      125, 15388-15394]. To the best of our knowledge, this is the first report of the
      simulation of the time-resolved IR signal of a complex process occurring on a
      long (microsecond) time scale.

PMID- 25777155
TI  - Reversal of PSA progression on abiraterone acetate through the administration
      with food in men with metastatic castration-resistant prostate cancer.
AB  - BACKGROUND: Owing to efficacy and tolerability, abiraterone acetate (AA) is a
      leading treatment for men with metastatic castration-resistant prostate cancer.
      Increased serum concentrations of AA, such as by taking AA with food, may lead to
      the inhibition of additional enzymes in the androgen synthesis pathway implicated
      in castration-resistant prostate cancer progression. METHODS: Medical records of
      men with metastatic castration-resistant prostate cancer (mCRPC) who received AA
      between 1 April 2011 and 31 December 2013 were retrospectively reviewed. The
      primary outcome was the percent of men with a rising PSA on AA who experienced
      any PSA decline within 3 months after changing the administration of AA from
      without food to with food. Secondary outcomes were median time on AA therapy in
      men who received AA therapy without food versus those that switched
      administration from without food to with food at PSA progression, and the percent
      of men who experienced any decline in serum testosterone concentration, and the
      rate of adverse events observed while taking AA with food. RESULTS: Nineteen men
      who switched AA administration from without food to with food and 41 patients who
      administered AA without food only were included in the study. Of those patients
      who took AA with food at PSA progression, a PSA decline was observed in 3 of the
      19 (16%) men, including 3 of the 14 men who had an initial response to AA (21%).
      Testosterone declined in five out of seven patients from pre-food levels. The
      median time on AA therapy was increased by nearly 100 days in patients who
      switched AA administration from without food to with food. No increases in
      toxicity were observed. CONCLUSION: Some men with mCRPC may benefit from taking
      AA with food. Further prospective comparative studies are needed to determine if
      changing AA administration is beneficial.

PMID- 25777156
TI  - Brief Report: Main Contribution of DRB1*04:05 Among the Shared Epitope Alleles
      and Involvement of DRB1 Amino Acid Position 57 in Association With Joint
      Destruction in Anti-Citrullinated Protein Antibody-Positive Rheumatoid Arthritis.
AB  - OBJECTIVE: The shared epitope is associated with increased joint destruction in
      rheumatoid arthritis (RA) as well as susceptibility to RA and the production of
      anti-citrullinated protein antibody (ACPA). However, previous studies addressing
      whether the association of the shared epitope with joint destruction is
      independent of ACPA have shown different results in different populations.
      Different allele distributions in the shared epitope may explain this ethnic
      heterogeneity. This study was undertaken to assess the associations of the shared
      epitope and HLA-DRB1*04:05, the most common shared epitope allele in the Japanese
      population, with joint destruction in patients with ACPA-positive RA. METHODS: A
      total of 861 patients with ACPA-positive RA who had not received any biologic
      agents were recruited from the institute of Rheumatology, Rheumatoid Arthritis
      cohort (sets 1 and 2) and the Kyoto University Rheumatoid Arthritis Management
      Alliance cohort (set 3). Joint destruction was assessed using the modified
      Sharp/van der Heijde score (SHS). The associations of the shared epitope alleles,
      HLA-DRB1*04:05, and other shared epitope allele groups with the SHS were analyzed
      in a linear regression analysis. Amino acid variations associated with the SHS
      were also analyzed. RESULTS: The shared epitope was significantly associated with
      an increased SHS (P = 0.0017). Although HLA-DRB1*04:05 was significantly
      associated with an increased SHS (P = 2.7 * 10(-5)), the group of other shared
      epitope alleles, including HLA-DRB1*01:01, did not show an association with the
      SHS in spite of sufficient power (P = 0.67). HLA-DRB1*04:05 was associated with
      joint destruction in a dose-dependent manner. Analyses of amino acid associations
      of HLA-DRB1 revealed that serine at position 57, recently shown to have a
      susceptibility effect for ACPA-positive RA in Asian populations, showed a
      significant association (P = 5.0 * 10(-6)). CONCLUSION: HLA-DRB1*04:05,
      characterized by serine at position 57, accounts for the detrimental association
      between the shared epitope and SHS in Japanese patients with ACPA-positive RA.

PMID- 25777157
TI  - Association between colonic diverticulosis and bowel symptoms: A case-control
      study of 1629 Asian patients.
AB  - BACKGROUND: It remains unclear whether diverticulosis, absent inflammation, is
      responsible for chronic bowel symptoms. We examined the association between bowel
      symptoms and asymptomatic diverticulosis. METHOD: This case-control study
      included 543 patients with diverticulosis and 1086 age and sex-matched controls
      (1:2) without diverticulosis on screening colonoscopy. Eleven symptoms (abdominal
      discomfort, hunger discomfort, borborygmus, abdominal distension, flatus,
      constipation, diarrhea, loose stools, hard stools, fecal urgency, and incomplete
      evacuation) were evaluated using a gastrointestinal symptoms rating scale (GSRS)
      at baseline and second questionnaire. Associations between diverticulosis and
      symptoms were estimated using odds ratios (ORs) and 95 confidence interval (CI).
      RESULTS: In multivariate analysis, constipation (OR, 0.85 [0.78-0.93]) and hard
      stools (OR, 0.86 [0.78-0.94]) were negatively associated with diverticulosis. The
      other nine symptoms showed no association with diverticulosis. Diverticulosis was
      negatively associated with constipation (OR, 0.93 [0.74-0.93]), hard stools (OR,
      0.85 [0.76-0.96]), and incomplete evacuation (OR, 0.88 [0.79-0.99]) in males, and
      positively associated with diarrhea (OR, 1.39 [1.14-1.69]) and loose stools (OR,
      1.28 [1.05-1.55]) in females. No bowel symptoms were positively associated with
      any of right-sided, left-sided, or bilateral diverticulosis. Test-retest
      reliability of GSRS (mean interval, 4.4 months) was moderate (Mean Kappa, 0.568)
      in males and good (Mean Kappa, 0.652) in females. CONCLUSIONS: This large,
      colonoscopy-based, case-control study demonstrated that neither constipation nor
      hard stools were associated with an increased risk of diverticulosis, regardless
      of diverticulum location. In females, but not males, diarrhea and loose stools
      were positively associated with diverticulosis. Long-term test-retest reliability
      suggested that these symptoms remain consistent over a given period.

PMID- 25777158
TI  - Intumescent flame-retardant and self-healing superhydrophobic coatings on cotton
      fabric.
AB  - Flame-retardant and self-healing superhydrophobic coatings are fabricated on
      cotton fabric by a convenient solution-dipping method, which involves the
      sequential deposition of a trilayer of branched poly(ethylenimine) (bPEI),
      ammonium polyphosphate (APP), and fluorinated-decyl polyhedral oligomeric
      silsesquioxane (F-POSS). When directly exposed to flame, such a trilayer coating
      generates a porous char layer because of its intumescent effect, successfully
      giving the coated fabric a self-extinguishing property. Furthermore, the F-POSS
      embedded in cotton fabric and APP/bPEI coating produces a superhydrophobic
      surface with a self-healing function. The coating can repetitively and
      autonomically restore the superhydrophobicity when the superhydrophobicity is
      damaged. The resulting cotton fabric, which is flame-resistant, waterproof, and
      self-cleaning, can be easily cleaned by simple water rinsing. Thus, the
      integration of self-healing superhydrophobicity with flame retardancy provides a
      practical way to resolve the problem of washing durability of the flame-retardant
      coatings. The flame-retardant and superhydrophobic fabric can endure more than
      1000 cycles of abrasion under a pressure of 44.8 kPa without losing its flame
      retardancy and self-healing superhydrophobicity, showing potential applications
      as multifunctional advanced textiles. 

PMID- 25777159
TI  - Construction and validation of a model to predict nonadherence to guidelines for
      prescribing antiplatelet therapy to hypertensive patients.
AB  - OBJECTIVE: To construct and validate a model to predict nonadherence to
      guidelines for prescribing antiplatelet therapy (NGAT) to hypertensive patients.
      METHODS: This 3 month prospective study was undertaken in 2007-2009 to determine
      whether 712 hypertensive patients were or were not being prescribed antiplatelet
      therapy. OUTCOME: NGAT according to clinical guidelines (just for patients in
      secondary prevention or with Systematic COronary Risk Evaluation (SCORE) >=10%).
      Secondary variables: Duration of hypertension (years), blood pressure (BP), age,
      gender, smoking, diabetes, dyslipidemia, cardiovascular disease, lipid
      parameters, SCORE. Of the whole sample 80% was used to construct the model and
      20% to validate it. To construct the model, we performed a multivariate logistic
      regression model which was adapted to be a scoring system with risk groups. The
      adjusted odds ratios (ORs) were obtained through the model. To validate the model
      we calculated the area under the ROC curve (AUC) and then compared the expected
      and the observed NGAT. The final model was adapted for use as a mobile
      application. RESULTS: NGAT: 18.5%, construction; 17.9%, validation. FACTORS:
      higher duration of hypertension diagnosis, higher systolic BP, older age, male
      gender, smoking, diabetes, dyslipidemia and cardiovascular disease. VALIDATION:
      AUC = 0.82 (95% CI: 0.74-0.90, p < 0.001), with no differences between the
      observed and the expected NGAT (p = 0.334). CONCLUSION: A tool was constructed
      and validated to predict NGAT. The associated factors were related with a greater
      cardiovascular risk. The scoring system has to be validated in other areas.

PMID- 25777160
TI  - Dispensing doctor practices and community pharmacies: exploring the quality of
      pharmaceutical services.
AB  - AIMS: This research sought (a) to investigate the similarities and differences in
      how pharmaceutical services are provided by community pharmacies (CPs) and
      dispensing doctor practices (DPs) and (b) to identify the issues relevant to
      determining the quality of pharmaceutical services in these settings. BACKGROUND:
      UK pharmaceutical services, including dispensing prescriptions and public health
      advice, can be provided from both (CP) and, in rural areas, (DP). While there is
      much similarity between CPs and DPs in the types of services provided, there is
      also the potential for variation in service quality across settings. METHODS: A
      postal questionnaire of DPs and CPs in South West England was conducted to
      provide a descriptive overview of pharmaceutical services across the settings. A
      subsection of questionnaire respondent sites were selected to take part in case
      studies, which involved documentary analyses, observation and staff interviews.
      FINDINGS: Survey response was 39% for CPs (52/134) and 48% (31/64) for DPs. There
      were three CP and four DP case study sites, with 17 staff interviews. More
      pharmacies than practices were open at the weekend and they had more staff
      trained above NVQ level 2. Both doctors and pharmacists saw themselves as
      medicines experts, as being accessible and having good relationships with
      patients. Workplace practices and organisational ethos varied both within and
      across settings, with good practice observed in both. Overall, CPs and DPs have
      much in common. Workplace culture and an evidence-based approach to checking
      prescriptions and error reporting need to be considered in future assessments of
      service quality.

PMID- 25777161
TI  - Influenza virus aggravates the ox-LDL-induced apoptosis of human endothelial
      cells via promoting p53 signaling.
AB  - Oxidized low-density lipoprotein (ox-LDL) is well recognized to play a key role
      in the development of atherosclerosis. And influenza virus infection has been
      also recognized to promote the atherosclerosis onset and progressing. However,
      little is known about the mechanism into it. In present study, we investigated
      the infection of A/Porto Rico/8/1934 (H1N1) (PR8) influenza virus in human
      endothelial Eahy926 cells, and determined the induction of apoptosis by the virus
      infection in the cell. Then we investigated the apoptosis induced by ox-LDL in
      Eahy926 cells, determined the influence of influenza virus infection on the ox
      LDL-induced apoptosis in Eahy926 cells. Results demonstrated that PR8 virus
      infected human endothelial Eahy926 cells, forming plaques and replicated
      efficiently in the cell. And the virus infection promoted apoptosis in the cell,
      upregulated cytchrome c release, activated caspase 3. And what's more, we found
      that combined PR8 virus infection and ox-LDL treatment promoted higher level of
      apoptosis and higher level of the activation of apoptosis-associated molecules.
      Further examination indicated that the p53 signaling was more significantly
      promoted by both treatments. Therefore, present study confirmed that influenza
      virus aggravated the ox-LDL-induced apoptosis of human endothelial Eahy926 cells
      via promoting p53 signaling.

PMID- 25777178
TI  - Reliability of radiographic measures in infants with clubfoot treated with the
      Ponseti method.
AB  - PURPOSE: The aim of this study was two-fold: (1) to determine if radiographic
      measures can be reliably made in infants being treated with the Ponseti method
      and (2) to document radiographic changes before and after Achilles tenotomy.
      METHODS: A retrospective radiographic and chart review was performed on children
      with clubfoot treated by the Ponseti method at a single institution over a 10
      year period. Five independent reviewers measured a series of angles from a
      lateral forced dorsiflexion radiograph taken prior to and following Achilles
      tenotomy. These measures were taken in triplicate to determine the intra- and
      inter-reader reliability of dorsiflexion, tibio-calcaneal, talo-calcaneal, and
      talo-first metatarsal angles. RESULTS: Thirty-six subjects (56 feet) were treated
      with the Ponseti method and met the inclusion criteria. The median (range) age of
      patients at the time of tenotomy was 52 (34-147) days. The intra-reader
      reliability [intra-rater correlation coefficient (ICC)] for each of the measured
      angles pre- and post-tenotomy ranged from 0.933 to 0.995 and 0.864 to 0.995,
      respectively. Similarly, the inter-reader reliabilities (ICC) ranged from 0.727
      for the pre-tenotomy (talo-calcaneal) to 0.950 for the post-tenotomy (talo-first
      metatarsal) angles. The mean differences between pre- and post-tenotomy
      radiographs were: dorsiflexion increase of 17 degrees , tibio-calcaneal angle
      increase of 19 degrees , talo-calcaneal angle increase of 9 degrees , and talo
      first metatarsal angle increase of 10 degrees  (p-value <=0.001 for all
      measurements except the talo-first metatarsal angle, with a p-value of 0.001).
      CONCLUSIONS: Reliable radiographic measures can be made from lateral dorsiflexion
      radiographs of clubfeet treated with the Ponseti method before and after Achilles
      tenotomy.

PMID- 25777177
TI  - Bariatric embolization of the gastric arteries for the treatment of obesity.
AB  - Obesity is a public health epidemic in the United States that results in
      significant morbidity, mortality, and cost to the health care system. Despite
      advancements in therapeutic options for patients receiving bariatric procedures,
      the number of overweight and obese individuals continues to increase. Therefore,
      complementary or alternative treatments to lifestyle changes and surgery are
      urgently needed. Embolization of the left gastric artery, or bariatric arterial
      embolization (BAE), has been shown to modulate body weight in animal models and
      early clinical studies. If successful, BAE represents a potential minimally
      invasive approach offered by interventional radiologists to treat obesity. The
      purpose of the present review is to introduce the interventional radiologist to
      BAE by presenting its physiologic and anatomic bases, reviewing the preclinical
      and clinical data, and discussing current and future investigations. 

PMID- 25777179
TI  - Hip decompression of unstable slipped capital femoral epiphysis: a systematic
      review and meta-analysis.
AB  - PURPOSE: Slipped capital femoral epiphysis (SCFE) is one of the most common
      adolescent hip conditions. Unstable SCFE is characterized by sudden and severe
      hip pain with the inability to weight bear, even with crutches. Osteonecrosis of
      the femoral head is increased in patients with unstable SCFE. The aim of our
      study was to systematically review the literature that compares hip decompression
      to no hip decompression of unstable SCFE. METHODS: We searched several databases
      from 1946 to 2014 for any observational or experimental studies that evaluated
      hip decompression and osteonecrosis of unstable SCFE. We performed a meta
      analysis using a random effects model to pool odds ratios (ORs) for the
      comparison of osteonecrosis between patients undergoing hip decompression and no
      hip decompression. We also investigated the type of hip decompression performed.
      Descriptive, quantitative, and qualitative data were extracted. RESULTS: Of the
      17 articles identified, nine studies (eight case series and one retrospective
      cohort study) were eligible for the meta-analysis, with a total of 302 unstable
      SCFE. The pooled OR = 0.91 of osteonecrosis between hip decompression and no hip
      decompression was in favor of hip decompression, but was not statistically
      significant [95 % confidence interval (CI): 0.47, 1.75; p = 0.54, I (2) = 0 %].
      No significant differences in the rates of osteonecrosis were detected in
      unstable SCFE with open and percutaneous hip decompression alone (OR = 0.97, 95 %
      CI: 0.36, 2.62; p = 0.69, I (2) = 19.1 %) or hip decompression with bony
      procedures (OR = 0.99, 95 % CI: 0.35, 2.79; p = 0.69, I (2) = 0 %). CONCLUSIONS:
      The cumulative evidence at present does not indicate an association between hip
      decompression and a lower rate of osteonecrosis of unstable SCFE. However, hip
      decompression of unstable SCFE remains an option that can potentially decompress
      the intracapsular hip pressure and optimize the blood flow to the femoral head.
      Thus, multicenter prospective cohort studies are required and will be able to
      answer this question with more certainty and a higher level of evidence. LEVEL OF
      EVIDENCE: Level III/IV.

PMID- 25777181
TI  - Computational approach to radiogenomics of breast cancer: Luminal A and luminal B
      molecular subtypes are associated with imaging features on routine breast MRI
      extracted using computer vision algorithms.
AB  - PURPOSE: To identify associations between semiautomatically extracted MRI
      features and breast cancer molecular subtypes. METHODS: We analyzed routine
      clinical pre-operative breast MRIs from 275 breast cancer patients at a single
      institution in this retrospective, Institutional Review Board-approved study. Six
      fellowship-trained breast imagers reviewed the MRIs and annotated the cancers.
      Computer vision algorithms were then used to extract 56 imaging features from the
      cancers including morphologic, texture, and dynamic features. Surrogate markers
      (estrogen receptor [ER], progesterone receptor [PR], human epidermal growth
      factor receptor-2 [HER2]) were used to categorize tumors by molecular subtype:
      ER/PR+, HER2- (luminal A); ER/PR+, HER2+ (luminal B); ER/PR-, HER2+ (HER2);
      ER/PR/HER2- (basal). A multivariate analysis was used to determine associations
      between the imaging features and molecular subtype. RESULTS: The imaging features
      were associated with both luminal A (P = 0.0007) and luminal B (P = 0.0063)
      molecular subtypes. No association was found for either HER2 (P = 0.2465) or
      basal (P = 0.1014) molecular subtype and the imaging features. A P-value of
      0.0125 (0.05/4) was considered significant. CONCLUSION: Luminal A and luminal B
      molecular subtype breast cancer are associated with semiautomatically extracted
      features from routine contrast enhanced breast MRI.

PMID- 25777180
TI  - Maternal obesity and metabolic risk to the offspring: why lifestyle interventions
      may have not achieved the desired outcomes.
AB  - Obesity during pregnancy is associated with an increased risk of short- and long
      term metabolic dysfunction in the mother and her offspring. Both higher maternal
      pregravid body mass index (kg m(-2)) and excessive gestational weight gain (GWG)
      have been associated with adverse pregnancy outcomes such as gestational
      diabetes, preeclampsia and fetal adiposity. Multiple lifestyle intervention
      trials consisting of weight management using various diets, increased physical
      activity and behavioral modification techniques have been employed to avoid
      excessive GWG and improve perinatal outcomes. These randomized controlled trials
      (RCTs) have achieved modest success in decreasing excessive GWG, although the
      decrease in GWG was often not within the current Institute of Medicine
      guidelines. RCTs have generally not had any success with decreasing the risk of
      maternal gestational diabetes (GDM), preeclampsia or excessive fetal growth often
      referred to as macrosomia. Although the lack of success for these trials has been
      attributed to lack of statistical power and poor compliance with study protocols,
      our own research suggests that maternal pregravid and early pregnancy metabolic
      condition programs early placenta function and gene expression. These alterations
      in maternal/placental function occur in the first trimester of pregnancy prior to
      when most intervention trials are initiated. For example, maternal accrural of
      adipose tissue relies on prior activation of genes controlling lipogenesis and
      low-grade inflammation in early pregnancy. These metabolic alterations occur
      prior to any changes in maternal phenotype. Therefore, trials of lifestyle
      interventions before pregnancy are needed to demonstrate the safety and efficacy
      for both the mother and her offspring.

PMID- 25777182
TI  - A retrospective analysis of negative diffusion-weighted image results in patients
      with acute cerebral infarction.
AB  - We aimed to investigate the clinicoradiologic determinants of negative diffusion
      weighted image (DWI) results in patients with acute cerebral infarction (ACI).
      The medical records were reviewed of ACI patients. Patients were divided to the
      DWI positive and negative group. Positive DWI was used as independent variable
      and patients' clinicoradiologic factors were used as co-variables for
      multivariate logistic regression analysis. 349 patients received initial cerebral
      MRI within 72 hours of admission. Lacunar infarction was most common (42.1%)
      followed by posterior circulation infarction (30.1%) and partial anterior
      circulation infarction (18.1%). The majority of the patients (72.2%) had an NIHSS
      score of less than 5 at admission. 316 patients (90.54%) were positive on initial
      DWI. Patients with smoking, initial SBP >= 140 or DBP >= 90 mmHg, initial fasting
      plasma glucose (FPG) >= 7.0 mmol/L, initial MRI from onset of disease >1 d and
      anterior circulation infarction were liable to show positive DWI. Furthermore,
      DWI negative patients had significantly lower NIHSS scores (IQR 0,1,2) than DWI
      positive patients (IQR 1,2,4) (P = 0.000) at two weeks post onset of acute
      cerebral infarction. In conclusion, multiple clinicoradiologic factors are
      associated with negative and positive DWI and further delineation of these
      factors is required in future prospective studies.

PMID- 25777183
TI  - INSECTICIDAL AND OXIDATIVE EFFECTS OF AZADIRACHTIN ON THE MODEL ORGANISM Galleria
      mellonella L. (LEPIDOPTERA: PYRALIDAE).
AB  - The insecticidal effects, specifically, changes in hemolymph total protein and
      malondialdehyde (MDA) levels, and antioxidant enzyme activities of azadirachtin
      (AZA) given to the wax moth, Galleria mellonella L. (Lepidoptera: Pyralidae)
      larvae via force feeding were investigated. Bioassays showed that the LD50 and
      LD99 (lethal dose) values of AZA were 2.1 and 4.6 MUg/larva, respectively.
      Experimental analyses were performed with five doses of AZA (0.5, 1, 1.5, 2, and
      3 MUg/larva). Total protein level in larval hemolymph increased at all AZA doses
      at 24 h whereas a considerable decrease was observed at 2 and 3 MUg/larva doses,
      and only an increase displayed at 1.5 MUg/larva at 72 h. The level of MDA
      increased at 2 and 3 MUg/larva doses at 24 h compared with controls. This trend
      was also observed at 1.5, 2, and 3 MUg/larva doses at 72 h and MDA levels were
      lower when compared with those of 24 h at all doses except for 1.5 MUg/larva
      dose. Catalase activity decreased at 1, 1.5, and 2 MUg/larva doses at 24 h
      whereas increased at all doses except for 0.5 MUg/larva at 72 h compared with
      controls. AZA led to a decline in superoxide dismutase activity at all
      experimental doses at 24 and 72 h except for 3 MUg/larva doses at 72 h. An
      increase in glutathione-S-transferase (GST) activity was evident at all AZA doses
      at 24 h. AZA displayed 68% decline in GST activity at 72 h post treatments when
      compared to 24 h. Consequently, We infer that the toxicity of AZA extends beyond
      its known actions in molting processes to redox homeostasis.

PMID- 25777184
TI  - Reliability and validity of a single-item rating scale to monitor medication
      adherence for people living with HIV and lower health literacy.
AB  - BACKGROUND: Monitoring medication adherence in clinical and research settings may
      be especially challenging for people with lower literacy skills. OBJECTIVE: The
      current study examined the measurement properties of a single-item rating scale
      (SIRS) for assessing medication adherence in a sample of 468 people living with
      HIV and lower health literacy skills. METHODS: Participants completed two
      versions (computerized and telephone interview) of an SIRS as well as unannounced
      monthly pill counts. We also collected measures of common correlates of adherence
      and obtained participants' HIV RNA viral load from medical records. RESULTS:
      Results indicated that the SIRS is time stable over one month (r = 0.46 to 0.52).
      There was limited evidence for modality effects between the computerized and
      phone administered SIRS. Associations with unannounced pill counts demonstrated
      concurrent and predictive validity of the SIRS, and criterion-related validity by
      associations with viral load. However, the SIRS also demonstrated inflated
      adherence estimates relative to unannounced pill counts and these discrepancies
      were greatest for persons of lower income and who reported alcohol use.
      CONCLUSIONS: A simple SIRS to monitor medication adherence may therefore be
      reliable and valid for use with people challenged by lower literacy skills in
      both clinical and research settings.

PMID- 25777185
TI  - The maraviroc expanded access program - safety and efficacy data from an open
      label study.
AB  - PURPOSE: The maraviroc (MVC) expanded access program (EAP) was initiated to
      increase MVC availability to patients with limited treatment options. Darunavir
      (DRV), raltegravir (RAL), and etravirine (ETV) were either recently approved or
      under regulatory review at study initiation and available for coadministration
      with MVC. Thus, the safety of MVC in combination with new antiretroviral
      therapies (ARVs) could be assessed. This open-label safety study of MVC was
      conducted at 262 sites worldwide in 1032 R5 HIV-positive treatment-experienced
      patients with limited/no therapeutic options. METHODS: Study visits included
      screening, baseline, end of study or early discontinuation, and follow-up 30 days
      after last dose. Interim visits for HIV-1 RNA and CD4 cell counts occurred
      according to local HIV infection management guidelines. Safety data were analyzed
      overall and by subgroup based on ARV combination [MVC+optimized background
      therapy (OBT), MVC +/- OBT+DRV/r, MVC +/- OBT+RAL, MVC +/- OBT+RAL+DRV/r, MVC +/-
      OBT+RAL+ETV +/- DRV/r]. RESULTS: Most (90.3%) adverse events (AEs) were of mild
      or moderate severity with few grade 3/4 events, discontinuations, or temporary
      discontinuations/dose reductions due to AEs or serious AEs. Similar results were
      observed across subgroups. Of treated patients, 79.9% and 50% had HIV-1 RNA < 400
      copies/ml and < 50 copies/ml respectively, at the end of the study, early
      termination visits, or at last known status. Tropism changes and selection of MVC
      resistant R5 virus, including high-level MVC dependence, were mechanisms of viral
      escape. CONCLUSION: MVC was well tolerated with virologic suppression observed in
      most patients.

PMID- 25777186
TI  - Effectiveness and safety of rilpivirine, a non-nucleoside reverse transcriptase
      inhibitor, in treatment-naive adults infected with HIV-1: a meta-analysis.
AB  - OBJECTIVES: The aim of this study was to determine the effectiveness and safety
      of rilpivirine in treatment-naive adults infected with HIV-1. METHODS: We ran
      duplicate searches of multiple databases and searchable websites of major HIV
      conferences (up to October 2013) to identify randomized controlled trials
      reporting the effectiveness and safety of rilpivirine in treatment-naive adults
      infected with HIV-1. Reference lists from retrieved articles were also reviewed.
      Data were extracted independently in duplicate using predefined data fields. All
      analyses used random-effects models to calculate the summary treatment effect
      estimates. RESULTS: Four randomized controlled trials with a total of 2522
      patients were included in the inclusion criteria. The primary efficacy endpoint
      was the proportion of patients with confirmed HIV-1 RNA levels of  < 50 copies/ml
      (viral load) at 48 weeks. Rilpivirine demonstrated non-inferior antiviral
      efficacy in viral load comparable with efavirenz at 48 weeks [relative risk (RR)
      = 1.03, 95% confidence interval (CI): 0.99-1.07]. The mean changes from baseline
      in CD4 count were similar in both rilpivirine and efavirenz (RR = 1.05, 95% CI:
      0.85-1.24). Rilpivirine showed higher and significant difference in virological
      failure rates comparing with the efavirenz group (RR = 1.70, 95% CI: 1.21-2.38).
      The incidences of the most commonly reported adverse events related to study
      medication, including rash, and neurological events, were lower with rilpivirine
      than with efavirenz (RR = 0.11, 95% CI: 0.03-0.33; RR = 0.52, 95% CI: 0.45-0.60,
      respectively). CONCLUSIONS: Current evidence suggests a range of favorable
      effects and a generally favorable safety profile of rilpivirine in treatment
      naive adults infected with HIV-1 at week 48.

PMID- 25777187
TI  - 96-week resistance analyses of the STaR study:
      rilpivirine/emtricitabine/tenofovir DF versus efavirenz/emtricitabine/tenofovir
      DF in antiretroviral-naive, HIV-1-infected subjects.
AB  - BACKGROUND: STaR (GS-US-264-0110) was a 96-week phase 3b study evaluating the
      safety and efficacy of two single-tablet regimens,
      rilpivirine/emtricitabine/tenofovir DF (RPV/FTC/TDF) and
      efavirenz/emtricitabine/tenofovir DF (EFV/FTC/TDF) in treatment-naive, HIV-1
      infected subjects. METHODS: Genotypic analyses (population sequencing) of HIV-1
      protease (PR) and reverse transcriptase (RT) were performed at screening;
      subjects with pre-existing resistance to study drugs were excluded. The protocol
      defined resistance analysis population had genotypic/phenotypic analyses at
      failure and baseline for PR and RT. RESULTS: Through week 96, the resistance
      analysis population included 24/394 subjects (6.1%) receiving RPV/FTC/TDF and
      9/392 subjects (2.3%) receiving EFV/FTC/TDF. In the RPV/FTC/TDF arm, HIV-1
      isolates from 21/394 subjects (5.3%) developed non-nucleoside reverse
      transcriptase inhibitor (NNRTI) and/or nucleoside reverse transcriptase inhibitor
      (NRTI) resistance mutations and 20/21 isolates had both NNRTI and NRTI genotypic
      and/or phenotypic resistance. In the EFV/FTC/TDF arm, isolates from 4/392
      subjects (1.0%) developed NNRTI and/or NRTI resistance mutations. Resistance
      development after week 48 was infrequent (1.0% RPV/FTC/TDF; 0.3% EFV/FTC/TDF).
      When stratified by baseline HIV-1 RNA <=  or >100 000 copies/ml, 9/260 (3.5%)
      versus 12/134 (9.0%) RPV/FTC/TDF-treated subjects and 3/250 (1.2%) versus 1/142
      (0.7%) EFV/FTC/TDF-treated subjects developed resistant isolates, respectively.
      Pre-existing NRTI- and NNRTI-associated resistance mutations (not related to
      study drugs) did not impact treatment response to either regimen. CONCLUSIONS:
      Resistance development to RPV/FTC/TDF consisted of NNRTI and NRTI mutations and
      was more frequent than resistance development to EFV/FTC/TDF through week 96.
      Emergent resistance after week 48 was infrequent in both arms. Within the
      RPV/FTC/TDF arm, resistance development was more frequent in subjects with
      baseline HIV-1 RNA >100 000 copies/ml compared to baseline HIV-1 RNA <= 100 000
      copies/ml.

PMID- 25777188
TI  - The pharmacokinetic profile of raltegravir-containing antiretroviral therapy in
      HIV-infected individuals over 60 years of age.
AB  - BACKGROUND: Antiretroviral safety and efficacy and may differ in older versus
      younger HIV-infected patients. The objective of this study was to assess the
      pharmacokinetic (PK) profile in older HIV-infected subjects (>60 years) switching
      combination antiretroviral therapy (cART) to a raltegravir (RAL) containing
      regimen. METHODS: Nineteen HIV-infected patients over 60 years of age on
      effective cART (HIV-RNA < 50 copies/ml) were enrolled in this prospective 24-week
      study. On day 1, patients switched to tenofovir/emtricitabine (245/200 mg once
      daily) and RAL (400 mg twice daily). On day 28, intensive PK sampling was
      undertaken in a fasted state and RAL plasma concentrations determined.
      Neurocognitive function was assessed at baseline and week 24 using a
      neuropsychological battery. RAL PK parameters were compared to those of two
      younger historical HIV-infected control groups that received twice-daily RAL co
      administered with darunavir/ritonavir (DRV/r) 800/100 once daily by nonlinear
      mixed effects modelling. RESULTS: In HIV-infected subjects over the age of 60
      (mean +/- SD age: 66 +/- 3.4 years, n = 19) switching to a RAL containing
      regimen, we observed no safety concerns, no plasma virological rebounds, and no
      differences in RAL apparent oral clearance when compared to younger HIV-infected
      populations (mean +/- SD age: 41 +/- 9.2 years, n = 38) based on population
      pharmacokinetic analysis. After 24 weeks of study therapy a decline in cognitive
      function was observed [change in (SD) global score of (0.91 (1.3), P = 0.018].
      CONCLUSIONS: No significant changes in RAL exposure associated with age were
      observed.

PMID- 25777189
TI  - Renal safety of coformulated tenofovir/emtricitabine vs other nucleoside
      analogues in combination therapy in antiretroviral-naive patients aged 50 years
      or older in Spain: The TRIP study.
AB  - OBJECTIVES: Our aim is to describe the impact of emtricitabine (FTC)/tenofovir
      (TDF) versus other nucleoside reverse transcriptase inhibitor (NRTIs)-based
      regimens on renal function of human immunodeficiency virus (HIV) naive patients
      >50 years old who started combination antiretroviral therapy (cART). DESIGN:
      National, retrospective cohort analysis of patients >50 years old when they
      started cART (January 1, 2006-December 31, 2009). METHODS: We compared renal
      safety (changes in estimated glomerular filtration rate [eGFR] during the first
      year, and time to renal events during 4 years of follow-up) in FTC/TDF versus non
      FTC/TDF users. Among FTC/TDF users, we compared protease inhibitors vs non
      nucleoside reverse transcriptase inhibitors and Lopinavir/ritonavir vs Efavirenz.
      RESULTS: We included 103 patients: median age: 54.9 years, 84% males, median CD4
      count 247 cells/MUl, median viral load 4.7 log; median follow up 18 months (max:
      48 months); 73 started with FTC/TDF and 30 with other NRTIs. Change in eGFR was
      significantly worse for ritonavir-boosted lopinavir (LPV/r) vs efavirenz (EFV)
      users in the FTC/TDF group (71.2 vs 98.9 ml/min/1.73 m(2) at month 12, P < 0.05).
      The risk of renal events (progression to an Chronic Kidney Disease Epidemiology
      Collaboration value < 60 ml/min/1.73 m(2) in subjects with baseline values >60)
      was comparable for FTC/TDF users and non users, but was higher and almost
      significant for LPV/r as compared to EFV users in the FTC/TDF group (adjusted
      hazard ratio 6.1, 95% CI 0.8-45.5). CONCLUSIONS: In our study with a population
      of HIV infected subjects >= 50 years old, renal safety was similar for FTC/TDF
      and other NRTI-based regimens, but worse for LPV/r as compared to other regimens.

PMID- 25777190
TI  - Pushing the limit: examining factors that affect anoxia tolerance in a single
      genotype of adult D. melanogaster.
AB  - Drosophila melanogaster is a promiscuous species that inhabits a large range of
      harsh environments including flooded habitats and varying temperature changes. To
      survive these environments, fruit flies have adapted mechanisms of tolerance that
      allow them to thrive. During exposure to anoxic stress, fruit flies and other
      poikilotherms enter into a reversible, protective coma. This coma can be
      manipulated based on controlled environmental conditions inside the laboratory.
      Here we utilize a common laboratory raised strain of D. melanogaster to
      characterize adaptation abilities to better understand coma recovery and survival
      limitations. Our goal is to mimic the fly's natural environments (wet anoxia) and
      relate findings to a typical gas induced environment (dry anoxia) that is
      commonly used in a laboratory. Despite the abundance of research regarding acute
      and chronic anoxic exposure and cold stress, the literature is lacking evidence
      linking anoxic stress with variable environmental conditions such as animal age
      and stress duration. We present novel ways to assess coma recovery and survival
      using readily available laboratory tools. Our findings suggest that younger age,
      exposure to colder temperatures and wet environments increase resistance to
      anoxic stress. 

PMID- 25777246
TI  - Near-infrared emission of dibenzoxanthenium and its application in the design of
      nitric oxide probes.
AB  - Two dibenzoxanthenium derivatives bearing a 3,4-diaminophenyl group, compounds 1a
      and 1b, have been prepared and evaluated as near-infrared probes for the
      detection of nitric oxide. Compound 1a gave a 3-fold emission enhancement towards
      nitric oxide at 681 nm, whereas compound 1b exhibited OFF-ON emission behavior
      towards nitric oxide, resulting in a 35-fold increase in the fluorescence
      intensity with an emission maximum of 750 nm being approved through (TD)DFT
      calculations. Probe 1b showed independent emission in the presence of common
      cations, amino acids, reactive oxygen and nitrogen species; furthermore, it can
      be used for the in cellulo imaging of nitric oxide under acidic and neutral
      conditions.

PMID- 25777247
TI  - Safety and effectiveness of non-insulin glucose-lowering agents in the treatment
      of people with type 2 diabetes who observe Ramadan: a systematic review and meta
      analysis.
AB  - AIM: To determine which non-insulin glucose-lowering treatment regimens are most
      appropriate in people with type 2 diabetes who choose to fast during Ramadan.
      METHODS: Electronic databases were searched for randomized controlled trials
      (RCTs) and observational studies that compared non-insulin glucose-lowering
      agents in people with type 2 diabetes fasting during Ramadan. Those studies which
      reported hypoglycaemia, weight and glycated haemoglobin (HbA1c) change were
      included. Data were pooled using random effects models. RESULTS: A total of 16
      studies were included: 9 RCTs and 7 observational studies. There was evidence
      that dipeptidyl peptidase-4 (DPP-4) inhibitors led to fewer hypoglycaemic events
      compared with sulphonylureas. Sitagliptin significantly reduced the number of
      patients with >=1 hypoglycaemic episodes during Ramadan [risk ratio (RR) 0.48,
      95% confidence interval (CI) 0.36, 0.64; p > 0.0001]. This was not replicated in
      the RCTs of vildagliptin, but a significant reduction was found in the
      observational studies (RR 0.28, 95% CI 0.10, 0.75; p = 0.01) with high
      heterogeneity (I(2)  = 86.7%). Significant reductions in HbA1c and weight were
      seen in the observational studies of vildagliptin versus sulphonylureas. The use
      of liraglutide led to significant weight loss (-1.81 kg, 95% CI -2.91, -0.71; p =
      0.001) compared with sulphonylureas. Pioglitazone significantly increased weight
      compared with placebo (3.48 kg, 95% CI 2.82, 4.14; p < 0.0001). CONCLUSIONS: The
      analysis supports the use of DPP-4 inhibitors during Ramadan rather than
      sulphonylureas for reduction in hypoglycaemia without a cost to diabetes control
      and weight. The glucagon-like peptide (GLP)-1 agonist liraglutide provides
      clinical benefits, but more studies are required. RCTs of DPP-4 inhibitors
      compared with GLP-1 agonists and novel therapies including the sodium-glucose co
      transporter 2 and alpha-glucosidase inhibitors are needed to inform evidence
      based guidelines.

PMID- 25777248
TI  - Synthesis of Cu3Sn alloy nanocrystals through sequential reduction induced by
      gradual increase of the reaction temperature.
AB  - Cu3Sn alloy nanocrystals are synthesized by sequential reduction of Cu and Sn
      precursors through a gradual increase of the reaction temperature. By
      transmission electron microscopy (TEM), energy-dispersive X-ray spectroscopy
      (EDS), UV/Vis spectroscopy, and X-ray diffraction (XRD) analyses, the alloy
      formation mechanism of Cu3Sn nanocrystals has been studied. The incremental
      increase of the reaction temperature sequentially induces the reduction of Sn,
      the diffusion of Sn into the preformed Cu nanocrystals, resulting in the
      intermediate phase of Cu-Sn alloy nanocrystals, and then the formation of Cu3Sn
      alloy nanocrystals. We anticipate that the synthesis of Cu3Sn alloy nanocrystals
      encourages studies toward the synthesis of various alloy nanomaterials.

PMID- 25777251
TI  - Deficient habituation to repeated rectal distensions in irritable bowel syndrome
      patients with visceral hypersensitivity.
AB  - BACKGROUND: Irritable bowel syndrome (IBS) patients show evidence of altered
      central processing of visceral signals. One of the proposed alterations in
      sensory processing is an altered engagement of endogenous pain modulation
      mechanisms. The aim was to test the hypothesis that IBS patients with (IBS-S) and
      without visceral hypersensitivity (IBS-N) differ in their ability to engage
      endogenous pain modulation mechanism during habituation to repeated visceral
      stimuli. METHODS: Brain blood oxygen level dependent (BOLD) response was measured
      during repeated rectal distension and its anticipation in 33 IBS patients with
      and without visceral hypersensitivity and 18 healthy controls (HCs). BOLD
      response to early and late phase of the distension series was compared within and
      between groups. KEY RESULTS: While BOLD response was similar during the early
      phase of the experiment, IBS-S showed greater BOLD response than IBS-N and HCs
      during the late phase of the distension series. IBS-S showed increasing BOLD
      response both to the anticipation and delivery of low intensity rectal
      distensions in brain regions including insula, anterior and mid cingulate cortex.
      IBS-N showed decreasing BOLD response to repeated rectal distensions in brain
      regions including insula, prefrontal cortex and amygdala. CONCLUSIONS &
      INFERENCES: These findings are consistent with compromised ability of IBS-S to
      respond to repeated delivery of rectal stimuli, both in terms of sensitization of
      sensory pathways and habituation of emotional arousal. The fact that both IBS
      subgroups met Rome criteria, and did not differ in terms of reported symptom
      severity demonstrates that similar symptom patterns can result from different
      underlying neurobiological mechanisms.

PMID- 25777252
TI  - A quarter of a century of the DBQ: some supplementary notes on its validity with
      regard to accidents.
AB  - This article synthesises the latest information on the relationship between the
      Driver Behaviour Questionnaire (DBQ) and accidents. We show by means of computer
      simulation that correlations with accidents are necessarily small because
      accidents are rare events. An updated meta-analysis on the zero-order
      correlations between the DBQ and self-reported accidents yielded an overall r of
      .13 (fixed-effect and random-effects models) for violations (57,480 participants;
      67 samples) and .09 (fixed-effect and random-effects models) for errors (66,028
      participants; 56 samples). An analysis of a previously published DBQ dataset (975
      participants) showed that by aggregating across four measurement occasions, the
      correlation coefficient with self-reported accidents increased from .14 to .24
      for violations and from .11 to .19 for errors. Our meta-analysis also showed that
      DBQ violations (r = .24; 6353 participants; 20 samples) but not DBQ errors (r = -
      .08; 1086 participants; 16 samples) correlated with recorded vehicle speed.
      Practitioner Summary: The DBQ is probably the most widely used self-report
      questionnaire in driver behaviour research. This study shows that DBQ violations
      and errors correlate moderately with self-reported traffic accidents.

PMID- 25777253
TI  - Reply: To PMID 24798499.

PMID- 25777254
TI  - Relation Between Left Atrial Wall Thickness in Patients with Atrial Fibrillation
      and Intracardiac Electrogram Characteristics and ATP-Provoked Dormant Pulmonary
      Vein Conduction.
AB  - INTRODUCTION: Atrial remodeling plays a key role in development of the substrate
      for atrial fibrillation (AF). Whether the wall thicknesses of the left atrium
      (LA) and pulmonary vein (PV)-LA junction affect remodeling and AF ablation is
      unknown. We investigated the relationship between wall thicknesses, electrogram
      characteristics, and adenosine triphosphate (ATP)-provoked dormant PV conduction
      as they pertain to AF. METHODS: In 50 patients with AF and 25 patients without
      AF, wall thicknesses of the LA and PV-LA junction were measured on 320-slice
      computed tomography images. For the AF patients, NavX-based voltage maps
      generated during sinus rhythm were obtained, and ATP-provoked dormant PV
      conduction after PV isolation was evaluated. RESULTS: Walls of the LA and PV-LA
      junction were significantly thicker in the AF patients than in the control
      patients (1.83 +/- 0.29 mm vs. 1.59 +/- 0.28 mm, respectively; P = 0.0010; and
      0.88 +/- 0.14 mm vs. 0.65 +/- 0.11 mm, P<0.0001, respectively). Wall thickness at
      the PV-LA junction was independently associated with AF (beta = 0.40, P =
      0.0002). In AF patients, the walls of the PV-LA junction showed stepwise
      thickening across bipolar voltages indicative of severe (bipolar voltage <33rd
      percentile) to moderate (33rd-66th percentiles) to mild fibrosis/scarring (>=66th
      percentile). Walls of the PV-LA junction with dormant PV conduction were
      significantly thicker than those without it (0.94 +/- 0.19 mm vs. 0.86 +/- 0.21
      mm, respectively; P = 0.0025). CONCLUSIONS: Together, the association between
      thickened PV-LA junction walls and AF and the increased bipolar voltage suggests
      that such wall thickening increases PV electrical activities, leading to
      initiation and maintenance of AF and perhaps to ATP-provoked dormant PV
      conduction.

PMID- 25777255
TI  - Association of Physical Activity Measured by Accelerometer, Knee Joint
      Abnormalities, and Cartilage T2 Measurements Obtained From 3T Magnetic Resonance
      Imaging: Data From the Osteoarthritis Initiative.
AB  - OBJECTIVE: To study the cross-sectional association between physical activity
      measured with an accelerometer, structural knee abnormalities, and cartilage T2
      values assessed with 3T magnetic resonance imaging (MRI). METHODS: We included
      274 subjects from the Osteoarthritis Initiative cohort without definite
      radiographic osteoarthritis (Kellgren/Lawrence grades 0 and 1) and with at most
      mild pain, stiffness, and functional limitation in the study knee (Western
      Ontario and McMaster Universities Osteoarthritis Index scale 0-1), which had not
      limited their activity due to knee pain. Physical activity was measured over 7
      days with an ActiGraph GT1M accelerometer. Subjects were categorized by quartile
      of physical activity based on the average daily minutes of moderate to vigorous
      physical activity (mv-PA). MRI images of the right knee (at 48-month visit) were
      assessed for structural abnormalities using a modified Whole-Organ Magnetic
      Resonance Imaging Score (WORMS) and for T2 relaxation times derived from
      segmented cartilage of 4 femorotibial regions and the patella. WORMS grades and
      T2 measurements were compared between activity quartiles using a linear
      regression model. Covariates included age, sex, body mass index, knee injury,
      family history of knee replacement, knee symptoms, hip and ankle pain, and daily
      wear time of the accelerometer. RESULTS: Higher mv-PA was associated with
      increased severity (P = 0.0087) and number of lesions of the medial meniscus (P =
      0.0089) and with severity of bone marrow edema lesions (P = 0.0053). No
      association between cartilage lesions and mv-PA was found. T2 values of cartilage
      (loss, damage, and abnormalities) tended to be greater in the higher quartiles of
      mv-PA, but the differences were nonsignificant. CONCLUSION: In knees without
      radiographic osteoarthritis in subjects with no or mild knee pain, higher
      physical activity levels were associated with increases in meniscal and bone
      marrow edema pattern lesions.

PMID- 25777257
TI  - The osteochondral interface as a gradient tissue: from development to the
      fabrication of gradient scaffolds for regenerative medicine.
AB  - The osteochondral (OC) interface is not only the interface between two tissues,
      but also the evolution of hard and stiff bone tissue to the softer and
      viscoelastic articular cartilage covering the joint surface. To generate a smooth
      transition between two tissues with such differences in many of their
      characteristics, several gradients are recognizable when moving from the bone
      side to the joint surface. It is, therefore, necessary to implement such
      gradients in the design of scaffolds to regenerate the OC interface, so to mimic
      the anatomical, biological, and physicochemical properties of bone and cartilage
      as closely as possible. In the past years, several scaffolds were developed for
      OC regeneration: biphasic, triphasic, and multilayered scaffolds were used to
      mimic the compartmental nature of this tissue. The structure of these scaffolds
      presented gradients in mechanical, physicochemical, or biological properties. The
      use of gradient scaffolds with already differentiated or progenitor cells has
      been recently proposed. Some of these approaches have also been translated in
      clinical trials, yet without the expected satisfactory results, thus suggesting
      that further efforts in the development of constructs, which can lead to a
      functional regeneration of the OC interface by presenting gradients more closely
      resembling its native environment, will be needed in the near future. The aim of
      this review is to analyze the gradients present in the OC interface from the
      early stage of embryonic life up to the adult organism, and give an overview of
      the studies, which involved gradient scaffolds for its regeneration.

PMID- 25777256
TI  - p63 Expression in the Gerbil Hippocampus Following Transient Ischemia and Effect
      of Ischemic Preconditioning on p63 Expression in the Ischemic Hippocampus.
AB  - p63 is a transcription factor of p53 gene family, which are involved in
      development, differentiation and cell response to stress; however, its roles in
      ischemic preconditioning (IPC) in the brain are not clear. In the present study,
      we investigated the effect of IPC on p63 immunoreactivity caused by 5 min of
      transient cerebral ischemia in gerbils. IPC was induced by subjecting the gerbils
      to 2 min of transie ischemia 1 day prior to 5 min of transient ischemia. The
      animals were randomly assigned to four groups (sham-operated-group, ischemia
      operated-group, IPC plus (+)-sham-operated-group and IPC + ischemia-operated
      group). The number of viable neurons in the stratum pyramidale of the hippocampal
      CA1 region (CA1) was significantly increased by IPC + ischemia-operated-group
      compared with that in the ischemia-operated-group 5 days after ischemic insult.
      We found that strong p63 immunoreactivity was detected in the CA1 pyramidal
      neurons in the sham-operated-group, and the immunoreactivity was decreased with
      time after ischemia-reperfusion. In addition, strong p63 immunoreactivity was
      newly expressed in microglial cells of the CA1 region from 2 days after ischemia
      reperfusion. In all the IPC + sham-operated-groups, p63 immunoreactivity in the
      CA1 pyramidal neurons was similar to that in the sham-operated-group, and the
      immunoreactivity was well maintained in the IPC + ischemia-operated-groups after
      cerebral ischemia. In brief, our present findings show that IPC dramatically
      protected the reduction of p63 immunoreactivity in the pyramidal neurons of the
      CA1 region after ischemia-reperfusion, and this result suggests that the
      expression of p63 may be necessary for neurons to survive after transient
      cerebral ischemia.

PMID- 25777258
TI  - The Presence of Portal Vein Thrombosis Alters the Classic Enhancement Associated
      with Diagnosis of Hepatocellular Carcinoma.
AB  - AIMS: To determine whether the presence of portal vein thrombosis (PVT) where
      venous flow within the liver may be altered may delay the diagnosis of HCC and be
      associated with more advanced disease. We characterized the incidence and imaging
      characteristics of patients diagnosed with hepatocellular carcinoma in a cohort
      of patients with PVT compared with those without PVT. METHODS: This is a single
      center retrospective study of a subset of HCC patients who underwent dynamic
      imaging for HCC screening and were found to have PVT. Data abstracted included
      demographic data, TNM stage, number/type of scans, AFP level, MELD score, and
      time to diagnosis. RESULTS: Eighty-two patients newly diagnosed with HCC on
      screening were reviewed, of which 37 % (30/82) were found to have portal vein
      thrombosis. Patients with PVT had higher rates of atypical imaging associated
      with HCC compared with those without PVT (83 vs 56 %, p = 0.01) and had lower
      rates of portal venous washout (23 % vs 50 %, p = 0.018). Patients with PVT and
      HCC were also diagnosed at later TNM stage than those without PVT (70 vs 23 %, p
      < 0.001) and were significantly less likely to receive orthotopic liver
      transplant (3.6 vs 42 %, p < 0.001). Fourteen patients had preexisting PV clot
      without HCC; 16 developed PVT during screening or at diagnosis. Those with
      preexisting PVT were older (63. vs 55 years) and had higher rates of diagnosis of
      HCC using MRI (79 vs 21 % with CT, p = 0.01), compared with those without
      preexisting PVT. CONCLUSION: The presence of PVT found on dynamic imaging was
      associated with advanced stage of HCC at the time of diagnosis. Clinicians should
      have a high suspicion for HCC diagnosis in new liver lesions with atypical
      enhancement in the setting of PVT. In this setting, MRI was more frequently
      associated with HCC diagnosis.

PMID- 25777259
TI  - Hyperglycemia Promotes Human Gastric Carcinoma Progression via Aquaporin 3.
AB  - BACKGROUND: Hyperglycemia plays an important role in the development of gastric
      carcinoma (GC). Aquaporin 3 (AQP3) is overexpressed in GC and involved in
      carcinogenesis and progression of GC. Hyperglycemia promotes AQP3 expression in
      human peritoneal mesothelial cells. AIMS: To investigate whether hyperglycemia
      promotes progression of GC via AQP3. METHODS: We enrolled 978 patients with GC
      and evaluated the correlation between preoperative fasting plasma glucose and
      clinicopathological features. AQP3 was detected by immunohistochemistry in human
      GC specimens. Western blotting and real-time quantitative polymerase chain
      reaction evaluated changes in AQP3 expression in human GC MGC803 and SGC7901
      cells after co-culture with high glucose. Transwell migration and Cell Counting
      Kit-8 assays were used to determine migration and proliferation of GC cells.
      RESULTS: Hyperglycemia (fasting plasma glucose >=6.1 mM) correlated with tumor
      size, location, and pTNM stage. AQP3 expression in tumor tissue was associated
      with fasting plasma glucose levels. High glucose concentration upregulated AQP3
      expression in a dose- and time-dependent manner. High glucose concentration
      promoted GC cell migration markedly, and AQP3 knockdown with siRNA could abolish
      the increase in cell migration. However, high glucose concentration inhibited
      cell proliferation, and AQP3 knockdown significantly enhanced the inhibitory
      effect of high glucose. The ERK and PI3K/AKT signaling pathways were involved in
      high glucose regulation of AQP3 in human GC cells. CONCLUSION: Hyperglycemia
      promotes GC progress via AQP3. This improves our understanding of the mechanism
      of hyperglycemia-induced carcinogenesis and provides a potential therapeutic
      strategy for GC.

PMID- 25777260
TI  - Suboptimal Bowel Preparation Significantly Impairs Colonoscopic Detection of Non
      polypoid Colorectal Neoplasms.
AB  - BACKGROUND: It is unclear whether the quality of bowel preparation affects
      colonoscopic detection of non-polypoid colorectal neoplasms (NP-CRNs). AIM: To
      evaluate the impact of bowel-cleansing quality on detection of NP-CRNs. METHODS:
      We performed a retrospective analysis of asymptomatic screening colonoscopy cases
      after standardized bowel preparation at an academic teaching hospital between
      June 2011 and May 2013. Primary outcome was a comparison of the adenoma detection
      rate (ADR) of non-polypoid morphology according to quality of bowel preparation.
      Secondary outcomes included detection prevalence of non-polypoid adenomas.
      RESULTS: Of the enrolled 6097 screening examinations, the preparation quality was
      rated as adequate (excellent or good) in 5224 (85.7 %), fair in 615 (10.1 %), and
      poor in 258 (4.2 %) patients. The prevalence of NP-CRNs was 40.5 % (1962/4847) of
      all CRNs. The overall ADR of non-polypoid morphology was 12.3 % (747/6097) of all
      colonoscopies, but it significantly differed among participating endoscopists
      (all P < 0.05). The ADR of non-polypoid morphology was significantly lower with
      fair- or poor-quality preparation, versus adequate-quality preparation (adjusted
      odds ratio [aOR] 0.55, 95 % confidence interval [CI] 0.41-0.75; aOR 0.49, 95 % CI
      0.30-0.79, respectively). Poor-quality preparation was also associated with
      impaired detection of polypoid, proximal colon, and sub-centimeter adenomas (all
      P < 0.05). CONCLUSIONS: Suboptimal (fair or poor) bowel preparation significantly
      impairs colonoscopic detection of NP-CRNs. Given that the prevalence of NP-CRNs
      is substantial in our average-risk screening cohort, ongoing efforts to improve
      the preparation quality are practically valuable in increasing the detection of
      NP-CRNs, thereby improving the efficacy of screening colonoscopies.

PMID- 25777261
TI  - The limits of serial surveillance cultures in predicting clearance of
      colonization with carbapenemase-producing Enterobacteriaceae.
AB  - An accepted practice for patients colonized with multidrug-resistant organisms is
      to discontinue contact precautions following 3 consecutive negative surveillance
      cultures. Our experience with surveillance cultures to detect persistent
      carbapenemase-producing Enterobacteriaceae (CPE) colonization suggests that
      extrapolation of this practice to CPE-colonized patients may not be appropriate.

PMID- 25777262
TI  - Optimisation of alpha-terpineol production by limonene biotransformation using
      Penicillium digitatum DSM 62840.
AB  - BACKGROUND: In this study, (R)-(+)-limonene biotransformation using three fungal
      strains was compared. Penicillium digitatum DSM 62840 was distinguished for its
      capacity to transform limonene into alpha-terpineol with high regioselectivity.
      Growth kinetics in submerged liquid culture and the effects of growth phase and
      contact time on biotransformation were studied using this strain. Substrate
      concentration, co-solvent selection, and cultivation conditions were subsequently
      optimised. RESULTS: The maximum concentration of alpha-terpineol (833.93 mg L(
      1)) was obtained when the pre-culture medium was in medium log-phase by adding
      840 mg L(-1) substrate dissolved in ethanol and cultivation was performed at 24 
      degrees C, 150 rpm, and pH 6.0 for 12 h. Addition of small amounts of (R)-(+)
      limonene (84 mg L(-1)) at the start of fungal log-phase growth yielded a 1.5-fold
      yield of alpha-terpineol, indicating that the enzyme was inducible. CONCLUSION:
      Among these three strains tested, P. digitatum DSM 62840 was proved to be an
      efficient biocatalyst to transform (R)-(+)-limonene to alpha-terpineol. Further
      studies revealed that the optimal growth phase for biotransformation was in the
      medium log phase of this strain. The biotransformation represented a wide
      tolerance of temperature; alpha-terpineol concentration underwent no significant
      change at 8-32  degrees C. The biotransformation could also be performed using
      resting cells.

PMID- 25777263
TI  - Screening Feature Genes of Venous Thromboembolism with DNA Microarray.
AB  - We aimed to explore the potential genes or pathways related to venous
      thromboembolism (VTE) and expected our findings could contribute to the
      development of new target drugs for VTE. The gene expression profile of GSE19151
      was downloaded from Gene Expression Omnibus (GEO) database. The bioinformatics
      methods were applied to screen the feature genes and pathways related with VTE. A
      total of 115 DEGs were identified, including 25 downregulated genes and 90
      upregulated genes. Function enrichment analysis showed that upregulated genes of
      VTE were mainly enriched in ribosome and translation-related pathways, while
      downregulated genes were mainly enriched in cytoskeletal protein binding and non
      membrane-bounded organelle-related pathways. MCL1, TP53, and RERE were three
      outstanding genes involved in the interaction network. The most significant
      pathways enriched by module genes were ribosome and oxidative phosphorylation.
      Moreover, all the products of the 18 genes enriched in ribosome (hsa03010) were
      ribosomal proteins. Ribosome, translation, actin binding, and non-membrane
      bounded organelle pathways were closely related to the development of VTE.
      Moreover, MCL1, TP53, and RERE might play key roles in the process of VTE. 

PMID- 25777265
TI  - Antioxidant and anti-inflammatory activities of zinc oxide nanoparticles
      synthesized using Polygala tenuifolia root extract.
AB  - The exploitation of various plant materials for the green synthesis of
      nanoparticles is considered an eco-friendly technology because it does not
      involve toxic chemicals. In this study, zinc oxide nanoparticles (ZnO NPs) were
      synthesized using the root extract of Polygala tenuifolia. Synthesized ZnO NPs
      were characterized by UV-Vis spectroscopy, FTIR, TGA, TEM, SEM and EDX. Anti
      inflammatory activity was investigated in LPS-stimulated RAW 264.7 macrophages,
      whereas antioxidant activity was examined using a DPPH free radical assay. ZnO
      NPs demonstrated moderate antioxidant activity by scavenging 45.47% DPPH at
      1mg/mL and revealed excellent anti-inflammatory activity by dose-dependently
      suppressing both mRNA and protein expressions of iNOS, COX-2, IL-1beta, IL-6 and
      TNF-alpha. 

PMID- 25777264
TI  - Could training executive function improve treatment outcomes for eating
      disorders?
AB  - Current gold standard treatments for eating disorders (EDs) lack satisfactory
      efficacy, and traditional psychological treatments do not directly address
      executive functioning deficits underpinning ED pathology. The goal of this paper
      is to explore the potential for enhancing ED treatment outcomes by improving
      executive functioning deficits that have been demonstrated to underlie eating
      pathology. To achieve our objective, we (1) review existing evidence for
      executive functioning deficits that underpin EDs and consider the extent to which
      these deficits could be targeted in neurocognitive training programs, (2) present
      the evidence for the one ED neurocognitive training program well-studied to date
      (Cognitive Remediation Therapy), (3) discuss the utility of neurocognitive
      training programs that have been developed for other psychiatric disorders with
      similar deficits, and (4) provide suggestions for the future development and
      research of neurocognitive training programs for EDs. Despite the fact that the
      body of empirical work on neurocognitive training programs for eating disorders
      is very small, we conclude that their potential is high given the combined
      evidence for the role of deficits in executive functioning in EDs, the initial
      promise of Cognitive Remediation Training, and the success in treating related
      conditions with neurocognitive training. Based on the evidence to date, it
      appears that the development and empirical evaluation of neurocognitive training
      programs for EDs is warranted.

PMID- 25777266
TI  - Anti-thrombotic effect of rutin isolated from Dendropanax morbifera Leveille.
AB  - Dendropanax morbifera H. Lev. is well known in Korean traditional medicine for
      improvement of blood circulation. In this study, rutin, a bioflavonoid having
      anti-thrombotic and anticoagulant activities was isolated from a traditional
      medicinal plant, D. morbifera H. Lev. The chemical characteristics of rutin was
      studied to be quercetin 3-O-alpha-l-rhamnopyranosyl-(1-6)-beta-d-glucopyranoside
      using high performance liquid chromatography mass spectrometry (HPLC-MS), proton
      nuclear magnetic resonance ((1)H NMR) and carbon-13 nuclear magnetic resonance
      ((13)C NMR). Turbidity and fibrin clotting studies revealed that rutin reduces
      fibrin clot in concentration dependent manner. Rutin was found to prolong
      activated partial thromboplastin time (aPTT), prothrombin time (PT) and closure
      time (CT). Furthermore, it decreased the activity of pro-coagulant protein,
      thrombin. In vivo study showed that rutin exerted a significant protective effect
      against collagen and epinephrine (or thrombin) induced acute thromboembolism in
      mice. These results suggest that rutin has a potent to be an anti-thrombotic
      agent for cardiovascular diseases.

PMID- 25777267
TI  - Determination and quantification of kokumi peptide, gamma-glutamyl-valyl-glycine,
      in brewed alcoholic beverages.
AB  - Recently, it has been demonstrated that kokumi substances such as glutathione are
      perceived through the calcium-sensing receptor (CaSR), and screening by CaSR
      assay and sensory evaluation has shown that gamma-glutamyl-valyl-glycine (gamma
      Glu-Val-Gly) is a potent kokumi peptide. In this study, gamma-Glu-Val-Gly
      contents in various brewed alcoholic beverages were investigated. Contents of
      gamma-Glu-Val-Gly in four brands of wine, four brands of rice wine (sake) and
      eight brands of beer were analyzed by high performance liquid chromatography
      tandem mass spectrometry followed by derivatization with 6-aminoquinoyl-N
      hydroxysuccinimidyl-carbamate. The analyses indicated that gamma-Glu-Val-Gly was
      present in all of eight beer samples at concentrations in the range of 0.08-0.18
      mg/L, although the peptide was not detected in any wine or rice wine samples.
      These results suggest that amongst the brewed beverages tested, beer contains
      gamma-Glu-Val-Gly, and that gamma-Glu-Val-Gly is widely distributed in beer. 

PMID- 25777269
TI  - 3D time-resolved vessel-selective angiography based on pseudo-continuous arterial
      spin labeling.
AB  - Angiographic imaging is an important diagnostic tool for the assessment of the
      intracranial arterial status. Using arterial spin labeling (ASL) techniques, it
      is possible to visualize the arteries without the administration of exogenous
      contrast agents. Moreover, modifications of the labeling method allow for the
      visualization of single arterial trees. In this study, an approach is presented
      for time-resolved MR angiography based on superselective ASL and keyhole
      accelerated image acquisition in order to selectively visualize individual
      cerebral arteries in a clinically acceptable scan time. Keyhole percentage as
      well as the flip angle of the acquisition sequence was optimized in numerical
      simulations. Subsequently, the method was validated in healthy volunteers. As a
      result, image acquisition in 5 minutes with a temporal resolution of 100 ms and
      spatial resolution below 1 mm was achieved. 

PMID- 25777268
TI  - Mild, Pd-catalyzed stannylation of radioiodination targets.
AB  - Trialkylstannanes are versatile precursors for chemical transformations,
      including radiolabeling with a variety of halogens, particularly iodine. In the
      present work a convenient, Pd-mediated stannylation method is presented that can
      be performed in an open flask. The method is selective for aryl iodides allowing
      selective stannylations in the presence of other halogen atoms. The reaction
      conditions are mild, making the method compatible with chemically sensitive
      bioactive compounds. 

PMID- 25777270
TI  - A novel cognitive intervention for compulsive checking: Targeting maladaptive
      beliefs about memory.
AB  - BACKGROUND AND OBJECTIVES: Compulsive checking is one of the most common symptoms
      of obsessive-compulsive disorder (OCD). Recently it has been proposed that those
      who check compulsively may believe their memory is poor, rather than having an
      actual memory impairment. The current study sought to develop and assess a brief
      cognitive intervention focused on improving maladaptive beliefs about memory, as
      they pertain to both checking symptoms and memory performance. METHODS:
      Participants (N = 24) with a diagnosis of OCD and clinical levels of checking
      symptomatology were randomly assigned either to receive two weekly 1-hour therapy
      sessions or to self-monitor during a similar waitlist period. Time spent
      checking, checking symptoms, maladaptive beliefs about memory, and visuospatial
      memory were assessed both pre- and post-treatment/waitlist. RESULTS: Results
      showed that compared to the waitlist condition, individuals in the treatment
      condition displayed significant decreases in their maladaptive beliefs about
      memory and checking symptoms from pre- to post-intervention. They also exhibited
      increased recall performance on a measure of visuospatial memory. Changes in
      beliefs about memory were predictors of reduced post-intervention checking, but
      were not predictive of increased post-intervention memory scores. LIMITATIONS:
      The lack of long term follow-up data and use of a waitlist control leave
      questions about the stability and specificity of the intervention. CONCLUSIONS:
      Findings provide preliminary evidence that strategies targeting beliefs about
      memory may be worthy of inclusion in cognitive-behavioural approaches to treating
      compulsive checking.

PMID- 25777271
TI  - A novel variant of FGFR3 causes proportionate short stature.
AB  - OBJECTIVE: Mutations of the fibroblast growth factor receptor 3 (FGFR3) cause
      various forms of short stature, of which the least severe phenotype is
      hypochondroplasia, mainly characterized by disproportionate short stature.
      Testing for an FGFR3 mutation is currently not part of routine diagnostic testing
      in children with short stature without disproportion. DESIGN: A three-generation
      family A with dominantly transmitted proportionate short stature was studied by
      whole-exome sequencing to identify the causal gene mutation. Functional studies
      and protein modeling studies were performed to confirm the pathogenicity of the
      mutation found in FGFR3. We performed Sanger sequencing in a second family B with
      dominant proportionate short stature and identified a rare variant in FGFR3.
      METHODS: Exome sequencing and/or Sanger sequencing was performed, followed by
      functional studies using transfection of the mutant FGFR3 into cultured cells;
      homology modeling was used to construct a three-dimensional model of the two
      FGFR3 variants. RESULTS: A novel p.M528I mutation in FGFR3 was detected in family
      A, which segregates with short stature and proved to be activating in vitro. In
      family B, a rare variant (p.F384L) was found in FGFR3, which did not segregate
      with short stature and showed normal functionality in vitro compared with WT.
      CONCLUSIONS: Proportionate short stature can be caused by a mutation in FGFR3.
      Sequencing of this gene can be considered in patients with short stature,
      especially when there is an autosomal dominant pattern of inheritance. However,
      functional studies and segregation studies should be performed before concluding
      that a variant is pathogenic.

PMID- 25777272
TI  - Pattern Recognition by CD6: A Scavenger-Like Lymphocyte Receptor.
AB  - CD6, one of the first antigens to be identified on T cells, is a membrane
      glycoprotein that physically associates with the antigen receptor complex.
      Because of this, its main function seems to involve the modulation of TCR
      mediated signaling pathways. However, growing evidence indicates that this
      ancient and conserved scavenger-like receptor may also play a role as pattern
      recognition receptor (PRR), similar to other members of the scavenger receptor
      cysteine rich superfamily (SRCR-SF). Here, we discuss the functional interactions
      of CD6 with microbe- and damage-associated signals and the potential use of
      soluble forms of CD6 in the therapeutic treatment of bacterial infections, in
      particular multi-drug resistant bacterial strains. Importantly, microbe
      recognition by CD6 may also have functional consequences on T cell activation and
      differentiation, which remain to be explored. 

PMID- 25777273
TI  - Metabotropic Glutamate Receptors in Central Nervous System Diseases.
AB  - Extensive research over the past thirty years has demonstrated a vital role for
      metabotropic glutamate (mGlu) receptors in the major functions of the central
      nervous system (CNS). A wealth of preclinical studies provide evidence that
      pharmacological targeting of mGlu receptors can effectively attenuate the
      development of symptoms and progression of many CNS disorders in animal models.
      In this review we summarize the current knowledge on the involvement of mGlu
      receptors in the pathophysiology of neuropsychiatric disorders (schizophrenia,
      depression, anxiety and cognitive disorders, pain perception and addiction), as
      well as neurodegenerative (Alzheimer's, Huntington's and Parkinson's diseases)
      and neurodevelopmental (fragile X syndrome and autism spectrum disorders)
      diseases. We further emphasize the therapeutic potential of mGlu receptors'
      pharmacological modulators in these diseases, describe the results of clinical
      trials with these compounds and discuss the potential sources of translational
      difficulties. 

PMID- 25777274
TI  - Targeting AMPK Signaling Pathway to Overcome Drug Resistance for Cancer Therapy.
AB  - Mulitdrug resistance (MDR) is one of critical factorslimiting the efficacy of
      cancer chemoor radiotherapy. Emerging evidence has indicated that MDR is a
      complex process regulated by multiple factors, among which stress response
      molecules are considered as central players. AMP-activated protein kinase (AMPK)
      is a major regulator balancing energy supply and ultimately protects cells from
      harmful stresses via coordinating multiple metabolic pathways Notably, AMPK
      activation was recently shown to mediate the metabolism reprogramming in drug
      resistant cancer cells including promoting Warburg effects and mitochondrial
      biogenesis. Furthermore, AMPK activity has also been shown to regulate the self
      renewal ability of cancer stem cells that are often refractory to chemotherapy.
      In addition, AMPK phosphorylation was critical in mediating autophagy induction,
      a process demonstrated to be effective in chemosensitivity modulation via
      degrading cellular components to satisfy nutrients requirement under stressful
      condition. Meanwhile, drug discovery targeting AMPK has been developed to
      validate the pathological significance of AMPK in cancer prevention and
      treatment. Although conflicting evidence focusing on the AMPK modulation for
      cancer treatment is still remained, this might be attributed to differences in
      AMPK isotypes in specific tissues, off-targets effects, the degree and duration
      of drug administration and experimental setting of stress conditions. This review
      will focus on AMPK mediated resistance to cancer therapy and discuss its
      potential therapeutic implication and targeting drug development.

PMID- 25777275
TI  - MicroRNAs and the Response of Prostate Cancer to Anti-Cancer Drugs.
AB  - Despite considerable advances in early diagnosis, prostate cancer (PCa) remains
      the second leading cause of cancer-related deaths in men in western countries. In
      fact, although efficient therapies exist for early-stage disease, the treatment
      of advanced PCa remains unsuccessful mainly due to its poor responsiveness to
      anti-cancer agents. This evidence underlines the urgent need for the development
      of novel and more effective therapeutic approaches. In this context, the
      documented dysregulation of microRNAs (miRNAs)--which are short non-coding RNAs
      that regulate gene expression at post-transcriptional level- in PCa, together
      with their potential to simultaneously regulate multiple oncogenic/ tumor
      suppressive pathways, has stimulated interest in defining a functional
      association between altered expression of specific miRNAs and the response of PCa
      to anti-cancer agents. The purpose of this review is to provide an overview on
      PCa-related miRNAs as potential novel therapeutic targets/tools, with a special
      focus on the role that they may play in conditioning the responsiveness of PCa to
      anti-cancer drugs.

PMID- 25777276
TI  - Molecular pathophysiology of cavernous nerve injury and identification of
      strategies for nerve function recovery after radical prostatectomy.
AB  - Despite nerve-sparing techniques, erectile dysfunction remains commonly observed
      after radical prostatectomy due to neuropraxia to the cavernous nerves during
      surgery. Preservation and rehabilitation of erectile function after radical
      prostatectomy remains challenging and many men stay undertreated with the current
      armory of therapies available in clinical practice. In this article we provide a
      comprehensive overview of the pathophysiology of the nerve injury occurring
      during radical prostatectomy and describe different strategies aimed at enhancing
      neuroprotection and regeneration of the cavernous nerves in order to improve
      erectile function recovery. These strategies include immunomodulatory,
      neurotrophic, growth factor and stem cell therapy have convincingly shown
      improved erectile function and recovery in rat animal models after cavernous
      nerve injury. Furthermore we describe the rationale for penile rehabilitation
      with PDE5i out of a neuronal recovery point of view. Many of these strategies
      reviewed have the potential to optimize erectile function recovery after radical
      prostatectomy when translated from pre-clinical models to clinical practice. 

PMID- 25777277
TI  - Update on lasers in urology 2015.

PMID- 25777278
TI  - Minimum 6 mm core length is strongly predictive for the presence of glandular
      tissue in transrectal prostate biopsy.
AB  - INTRODUCTION: Prostate biopsy guidelines recommend that a prostate biopsy not
      containing glandular prostate tissue should be reported as inadequate. In the
      literature, there is a lack of any study that addresses the relationship between
      the length of biopsy cores and the absence of glandular prostate tissue. In this
      study, we aimed to determine whether a relationship exists between these
      parameters. MATERIALS AND METHODS: We retrospectively evaluated 1,712 consecutive
      initial transrectal 12-core prostate biopsies. Individual cores were
      histologically categorized as glandular (benign or malignant) and non-glandular
      (rectal mucosa, periprostatic adipose tissue, prostatic or periprostatic
      fibromuscular tissue). Total number of evaluable cores <=9, highly fragmented,
      incorrectly numbered or dried biopsies, patients with 5-alpha reductase
      inhibitory treatment were excluded. RESULTS: We analyzed remaining 1,584
      patients; 41.7 % had adenocarcinoma. A total of 19,144 cores were sampled. Non
      glandular cores were found significantly shorter than glandular cores (p <
      0.0001). The percentages of non-glandular cores were significantly higher at the
      base, apex and lateral biopsy sites (p < 0.0001). We found a 6-mm cutoff value
      for accurate prediction of glandular sampling with 80.2 % sensitivity and 78.7 %
      specificity. The risk of non-glandular sampling increased 15-fold in cores <=6 mm
      (OR 14.91, 95% CI 13.20-16.83, p < 0.0001). CONCLUSIONS: Non-glandular sampling
      was directly associated with shorter core lengths. They were found significantly
      higher at the base, apex and lateral localizations. We found a 6-mm cutoff value
      for the prediction of non-glandular samples before the histologic evaluation.
      Below this value, the risk of non-glandular sampling increased 15-fold. We
      suggest it for prompt additional sampling during biopsy procedure.

PMID- 25777279
TI  - Thrombi in Takotsubo syndrome: Are there implications for management and
      cryptogenic thromboembolism in general?

PMID- 25777280
TI  - Brivudine induced coronary vasospasm as a manifestation of Kounis syndrome: First
      report.

PMID- 25777281
TI  - Isolation of the Pandorra's box and end of the evils in left atrium.

PMID- 25777282
TI  - Protease-activated receptor-1 antagonists in long-term antiplatelet therapy.
      Current state of evidence and future perspectives.
AB  - Atherothrombosis and its clinical manifestations are among the leading causes of
      death in the developed world. The current standard-of-care antiplatelet therapy
      for the treatment of such events comprises aspirin and a thienopyridine or
      ticagrelor. However, recurrent ischemic events due to residual cardiovascular
      risk are a common phenomenon in these patients. It is believed that this residual
      risk is caused, at least in part, by thrombin, which signals through protease
      activated receptors (PARs) and especially PAR-1. Thus, PAR-1 antagonism could
      represent an effective approach in the treatment of atherothrombotic disease. In
      this context, two potent and selective agents have been developed, vorapaxar and
      atopaxar. However, only vorapaxar has completed phase 3 clinical trials. In the
      present review, the main pharmacodynamic and pharmacokinetic properties of the
      PAR-1 antagonists are briefly described and the latest clinical data on vorapaxar
      are presented. 

PMID- 25777283
TI  - Association between red blood cell distribution width and postoperative atrial
      fibrillation after cardiac surgery: A pilot observational study.

PMID- 25777284
TI  - Direct aortic Direct Flow implantation via right anterior thoracotomy in a
      patient with patent bilateral mammary artery coronary grafts.

PMID- 25777285
TI  - Assessment of stent edge dissections by fractional flow reserve.
AB  - BACKGROUNDS: Edge dissections after intervention have been studied with imaging
      techniques, however, functional assessment has not been studied yet. We
      investigated the relationship between fractional flow reserve (FFR) and the
      angiographic type of stent edge dissections and tried to assess the use of FFR
      guided management for edge dissection. METHODS: 51 edge dissections assessed by
      FFR were included in this prospective observational study. FFR was measured for
      each type of edge dissection and compared with quantitative coronary angiographic
      findings. Clinical outcomes were evaluated based on FFR measurements. RESULTS:
      Edge dissections were classified as type A (47.1%; 24/51), type B (41.2%; 21/51),
      type C (2.0%; 1/51) and type D (9.8%; 5/51). Mean FFR in type A dissection was
      0.87 +/- 0.09, in type B 0.86 +/- 0.07, in type C 0.72 and in type D 0.57 +/-
      0.08. All type C and D dissections (6/51) had FFR <= 0.8 and were treated with
      additional stents. Among the 45 type A and B dissections, 8 had a FFR <= 0.8
      (17.8%), and 50% received additional stenting. All dissections with FFR >0.8 were
      left untreated except one long dissection case. There was no death, myocardial
      infarction or target lesion revascularization during hospitalization or the
      follow-up period (median 152 days; IQR 42-352 days). CONCLUSIONS: FFR correlates
      well with an angiographic type of edge dissection. Angiographic findings are
      sufficient for deciding the treatment of severe dissections such as types C and
      D, while FFR-guided management may be safe and effective for mild edge
      dissections such as types A and B.

PMID- 25777287
TI  - A novel approach for measuring social participation in adults who stutter.
AB  - This paper reports a preliminary study which trialled a novel approach for
      measuring speech output and social participation. The amount of phonation was
      accumulated via an objective measure called an Ambulatory Phonation Monitor
      (APM). PURPOSE: (1) To establish whether adults who stutter will tolerate wearing
      an APM for an extended period of time (three days), (2) to test whether the APM
      can accumulate useful data about the amount of phonation adults who stutter
      produce in the course of a normal day and (3) to examine a possible relationship
      between stuttering severity and amount of phonation. METHOD: Three adults who
      stutter wore an APM for three consecutive days during their waking hours. Each
      completed a questionnaire regarding the device and kept a speech diary outlining
      daily speaking activities and self-reported stuttering severity. APM data
      regarding amount of phonation was collected, analysed and compared with the
      participants' speech diaries. RESULTS: Each adult tolerated wearing the APM and
      while they felt comfortable speaking wearing the device, it was somewhat
      cumbersome. Variations in the amount of speaking across each day and in different
      speaking situations were evident. For two participants there was a positive
      correlation between phonation time and severity rating. CONCLUSIONS: Preliminary
      data suggests that the APM can provide valuable information about the amount
      adults who stutter speak. The APM is sufficiently sensitive to differentiate
      variations in the amount of phonation during different speaking situations. These
      favourable preliminary results suggest the value of a larger scale study.
      EDUCATIONAL OBJECTIVES: The reader will be able to: (a) describe the different
      aspects of stuttering currently routinely measured in clinical practice; (b)
      discuss the limitations of current measurement procedures; (c) discuss the
      advantages of speech measures obtained by an Ambulatory Phonation Monitor APM);
      (d) describe the perspectives of adults who stutter who have worn an APM to
      measure phonation time.

PMID- 25777286
TI  - Minocycline inhibits hyperpolarization-activated currents in rat substantia
      gelatinosa neurons.
AB  - Minocycline is a widely used glial activation inhibitor that could suppress pain
      related behaviors in a number of different pain animal models, yet, its analgesic
      mechanisms are not fully understood. Hyperpolarization-activated cation channel
      induced Ih current plays an important role in neuronal excitability and
      pathological pain. In this study, we investigated the possible effect of
      minocycline on Ih of substantia gelatinosa neuron in superficial spinal dorsal
      horn by using whole-cell patch-clamp recording. We found that extracellular
      minocycline rapidly decreases Ih amplitude in a reversible and concentration
      dependent manner (IC50 = 41 MUM). By contrast, intracellular minocycline had no
      effect. Minocycline-induced inhibition of Ih was not affected by Na(+) channel
      blocker tetrodotoxin, glutamate-receptor antagonists (CNQX and D-APV), GABAA
      receptor antagonist (bicuculine methiodide), or glycine receptor antagonist
      (strychnine). Minocycline also caused a negative shift in the activation curve of
      Ih, but did not alter the reversal potential. Moreover, minocycline slowed down
      the inter-spike depolarizing slope and produced a robust decrease in the rate of
      action potential firing. Together, these results illustrate a novel cellular
      mechanism underlying minocycline's analgesic effect by inhibiting Ih currents of
      spinal dorsal horn neurons.

PMID- 25777288
TI  - Organic breakdown products resulting from hydrothermal carbonization of brewer's
      spent grain.
AB  - Hydrothermal carbonization of brewer's spent grain resulted in a solid hydrochar
      and an aqueous phase rich in macromolecular dissolved organic matter. Both phases
      were analyzed with regard to low molecular weight organic compounds (MW<500 Da)
      in lyophilized form by exhaustive solvent extraction followed by pre
      chromatographic derivatization and GC/MS-analysis. Low molecular weight acids, O
      functionalized phenols, cyclopentenone derivatives, and benzenediols accounted
      for the majority of organic analytes in both hydrothermal carbonization product
      streams while being absent in solvent extracts of the pristine biomass. The
      pattern of short chain functionalized acids in the pristine biomass and in the
      hydrothermally produced matrices turned out very different. Acylglycerines as the
      most abundant lipids in pristine brewer's spent grain were quantitatively
      hydrolyzed under hydrothermal conditions. The recovery of total fatty acids
      present in the pristine biomass amounted to 19%. The major fraction of
      hydrophobic breakdown products including fatty acids, fatty alcohols, and sterols
      was sorbed onto the hydrochar.

PMID- 25777289
TI  - Obesity exacerbates imiquimod-induced psoriasis-like epidermal hyperplasia and
      interleukin-17 and interleukin-22 production in mice.
AB  - Psoriasis is a chronic inflammatory skin disorder that is accompanied by an
      imbalance between the proliferation and differentiation of keratinocytes. A
      number of studies have suggested an association between obesity and severe
      psoriasis; however, it remains to be clarified whether obesity exacerbates
      psoriasis. To address this unsolved question, we induced psoriasiform dermatitis
      in mouse models for obesity. We found that obesity exaggerated the severity of
      psoriasiform dermatitis induced by topical application of the Toll-like receptor
      (TLR) 7 agonist, imiquimod. Ear swelling and epidermal hyperplasia were more
      prominent in the obese mice than in the control mice. When compared to imiquimod
      treated control mice, imiquimod-treated obese mice expressed higher levels of
      psoriasis mediators, interleukin-17A (IL-17A) and IL-22 in the skin. Food intake
      restriction partially abrogated enhanced ear swelling and cytokine overproduction
      in obese mice. Furthermore, the obesity environment and imiquimod treatment
      synergistically induced an IL-17A downstream molecule, regenerating islet-derived
      3gamma (Reg3gamma), which is a critical molecule for psoriatic epidermal
      hyperplasia. Palmitic acid, one of the fatty acids released by subcutaneous
      adipocytes, increased the expression of REG3A (a human homologue of mouse
      Reg3gamma) in both the HaCaT keratinocyte cell line and normal human
      keratinocytes. Taken together, these results strongly suggest that obesity
      exacerbates psoriasiform dermatitis in mice by upregulating IL-17A, IL-22 and
      Reg3gamma. 

PMID- 25777290
TI  - Efficacy and safety of jollab to treat functional dyspepsia: a randomized placebo
      controlled clinical trial.
AB  - BACKGROUND: Functional dyspepsia (FD) is a common gastrointestinal disease that
      is highly prevalent worldwide. Because of its heterogeneous pathophysiology,
      treatment options for FD can be difficult to choose; in this context,
      complementary and alternative medicine modalities have been suggested as
      promising options. AIM: To evaluate the efficacy of a traditional Persian
      medicine, jollab, in reducing patients' FD symptoms. METHODS: In a double-blind
      randomized clinical trial, 160 patients with a diagnosis of FD were enrolled and
      treated with either jollab or placebo (15ml, t.i.d., four weeks, orally). The
      outcomes reported were changes in symptom frequency and severity as recorded in
      patients' diaries and evaluated with the Short Form of the Leeds Dyspepsia
      Questionnaire (SF-LDQ), and physical examination. RESULTS: The response rate was
      higher in the treatment group (78%) than in the placebo group (31%) according to
      per-protocol sample analysis (P < .001). Symptoms of FD disappeared significantly
      more frequently, and the rate of concomitant synthetic drug consumption was
      significantly lower, in the jollab group compared to the placebo group at the end
      of the trial. Mean total symptom frequency and severity according to the SF-LDQ
      score was 1.55 +/- 2.78 in the treatment group versus 5.61 +/- 3.80 in the
      placebo group at the last follow-up time point (P < .001). A promising safety
      profile for jollab was observed throughout the trial. CONCLUSIONS: In patients
      with FD, jollab appeared to be more effective than the placebo. Complementary and
      alternative therapies such as the use of this traditional medicinal substance may
      be beneficial in relieving symptoms of dyspepsia [ACTRN12613000584730].

PMID- 25777291
TI  - Adapting and using quality management methods to improve health promotion.
AB  - Although the western world is the most technologically advanced civilization to
      date, it is also the most addicted, obese, medicated, and in-debt adult
      population in history. Experts had predicted that the 21st century would be a
      time of better health and prosperity. Although wealth has increased, our quest to
      quell health problems using a pathogenic approach without understanding the
      interconnectedness of everyone and everything has damaged personal and planetary
      health. While current efforts help identify and eliminate causes of problems,
      they do not facilitate the creation of health and well-being as would be done
      with a salutogenic approach. Sociologist Aaron Antonovsky coined the term
      salutogenesis in 1979. It is derived from salus, which is Latin for health, and
      genesis, meaning to give birth. Salutogenesis, the study of the origins and
      creation of health, provides a method to identify an interconnected way to
      enhance well-being. Salutogenesis provides a framework for a method of practice
      to improve health promotion efforts. This article illustrates how quality
      management methods can be used to guide health promotion efforts focused on
      improving health beyond the absence of disease. 

PMID- 25777292
TI  - Warning dreams preceding the diagnosis of breast cancer: a survey of the most
      important characteristics.
AB  - BACKGROUND: There are rare reports of warning dreams about breast cancer in the
      dream literature and even fewer in the medical literature. Anxiety about breast
      cancer is increasing due to uncertainty about conflicting guidelines regarding
      mammography screening. OBJECTIVE: The purpose of the study was to survey women
      with breast cancer who had warning dreams prior to diagnosis to determine the
      most common and important characteristics of these dreams. METHODS: Eighteen
      women with a known diagnosis of breast cancer completed a survey of 19 Yes or No
      questions about their warning dreams and submitted dream narratives. RESULTS: The
      five most common characteristics of warning dreams in descending order of
      frequency reported in the survey were: a sense of conviction about the importance
      in 94%; the dreams were more vivid, real or intense than ordinary in 83%; an
      emotional sense of threat, menace or dread in 72%; the use of the specific words
      breast cancer/tumor in 44%; and the sense of physical contact with the breast in
      39%. CONCLUSION: Warning dreams of breast cancer were often reported to be life
      changing experiences that prompted medical attention leading directly to
      diagnosis. Further research needs to be done to determine the frequency of such
      dreams in women without known breast cancer in order to assess the predictive
      value of a warning dream. These preliminary results suggest that keeping a dream
      diary might be a useful adjunct to routine self-examination as part of a breast
      self-care program, particularly for women in a high-risk category.

PMID- 25777293
TI  - Biomechanical Characterization of a Model of Noninvasive, Traumatic Anterior
      Cruciate Ligament Injury in the Rat.
AB  - The onset of post-traumatic osteoarthritis (PTOA) remains prevalent following
      traumatic joint injury such as anterior cruciate ligament (ACL) rupture, and
      animal models are important for studying the pathomechanisms of PTOA. Noninvasive
      ACL injury using the tibial compression model in the rat has not been
      characterized, and it may represent a more clinically relevant model than the
      common surgical ACL transection model. This study employed four loading profiles
      to induce ACL injury, in which motion capture analysis was performed, followed by
      quantitative joint laxity testing. High-speed, high-displacement loading
      repeatedly induces complete ACL injury, which causes significant increases in
      anterior-posterior and varus laxity. No loading protocol induced valgus laxity.
      Tibial internal rotation and anterior subluxation occurs up to the point of ACL
      failure, after which the tibia rotates externally as it subluxes over the femoral
      condyles. High displacement was more determinative of ACL injury compared to high
      speed. Low-speed protocols induced ACL avulsion from the femoral footprint
      whereas high-speed protocols caused either midsubstance rupture, avulsion, or a
      combination injury of avulsion and midsubstance rupture. This repeatable,
      noninvasive ACL injury protocol can be utilized in studies assessing PTOA or ACL
      reconstruction in the rat. 

PMID- 25777294
TI  - Liver-Tumor Hybrid Organoids for Modeling Tumor Growth and Drug Response In
      Vitro.
AB  - Current in vitro models for tumor growth and metastasis are poor facsimiles of in
      vivo cancer physiology and thus, are not optimal for anti-cancer drug
      development. Three dimensional (3D) tissue organoid systems, which utilize human
      cells in a tailored microenvironment, have the potential to recapitulate in vivo
      conditions and address the drawbacks of current tissue culture dish 2D models. In
      this study, we created liver-based cell organoids in a rotating wall vessel
      bioreactor. The organoids were further inoculated with colon carcinoma cells in
      order to create liver-tumor organoids for in vitro modeling of liver metastasis.
      Immunofluorescent staining revealed notable phenotypic differences between tumor
      cells in 2D and inside the organoids. In 2D they displayed an epithelial
      phenotype, and only after transition to the organoids did the cells present with
      a mesenchymal phenotype. The cell surface marker expression results suggested
      that WNT pathway might be involved in the phenotypic changes observed between
      cells in 2D and organoid conditions, and may lead to changes in cell
      proliferation. Manipulating the WNT pathway with an agonist and antagonist showed
      significant changes in sensitivity to the anti-proliferative drug 5-fluoruracil.
      Collectively, the results show the potential of in vitro 3D liver-tumor organoids
      to serve as a model for metastasis growth and for testing the response of tumor
      cells to current and newly discovered drugs. 

PMID- 25777296
TI  - Inter-population differences in measuring: appreciation by adaptation.

PMID- 25777295
TI  - Umbilical Cord Blood-Derived Mononuclear Cells Exhibit Pericyte-Like Phenotype
      and Support Network Formation of Endothelial Progenitor Cells In Vitro.
AB  - Umbilical cord blood represents a promising cell source for pro-angiogenic
      therapies. The present study examined the potential of mononuclear cells (MNCs)
      from umbilical cord blood to support endothelial progenitor cell (EPC)
      microvessel formation. MNCs were isolated from the cord blood of 20 separate
      donors and selected for further characterization based upon their proliferation
      potential and morphological resemblance to human vascular pericytes (HVPs). MNCs
      were screened for their ability to support EPC network formation using an in
      vitro assay (MatrigelTM) as well as a reductionist, coculture system consisting
      of no additional angiogenic cytokines beyond those present in serum. In less than
      15% of the isolations, we identified a population of highly proliferative MNCs
      that phenotypically resembled HVPs as assessed by expression of PDGFR-beta, NG2,
      alpha-SMA, and ephrin-B2. Within a MatrigelTM system, MNCs demonstrated pericyte
      like function through colocalization to EPC networks and similar effects as HVPs
      upon total EPC tubule length (p = 0.95) and number of branch points (p = 0.93).
      In a reductionist coculture system, MNCs served as pro-angiogenic mural cells by
      supporting EPC network formation to a significantly greater extent than HVP
      cocultures, by day 14 of coculture, as evidenced through EPC total tubule length
      (p < 0.0001) and number of branch points (p < 0.0001). Our findings are
      significant as we demonstrate mural cell progenitors can be isolated from
      umbilical cord blood and develop culture conditions to support their use in
      microvascular tissue engineering applications. 

PMID- 25777298
TI  - The Power Decoder Simulator for the Evaluation of Pooled shRNA Screen
      Performance.
AB  - RNA interference screening using pooled, short hairpin RNA (shRNA) is a powerful,
      high-throughput tool for determining the biological relevance of genes for a
      phenotype. Assessing an shRNA pooled screen's performance is difficult in
      practice; one can estimate the performance only by using reproducibility as a
      proxy for power or by employing a large number of validated positive and negative
      controls. Here, we develop an open-source software tool, the Power Decoder
      simulator, for generating shRNA pooled screening experiments in silico that can
      be used to estimate a screen's statistical power. Using the negative binomial
      distribution, it models both the relative abundance of multiple shRNAs within a
      single screening replicate and the biological noise between replicates for each
      individual shRNA. We demonstrate that this simulator can successfully model the
      data from an actual laboratory experiment. We then use it to evaluate the effects
      of biological replicates and sequencing counts on the performance of a pooled
      screen, without the necessity of gathering additional data. The Power Decoder
      simulator is written in R and Python and is available for download under the GNU
      General Public License v3.0. 

PMID- 25777299
TI  - Evaluation of intra-aneurysmal hemodynamics after flow diverter placement in a
      patient-specific aneurysm model.
AB  - BACKGROUND: The growth and rupture of cerebral aneurysms is intrinsically related
      to the hemodynamics prevailing in the diseased area. Therefore, a better
      understanding of intra-aneurysmal hemodynamics is essential for developing
      effective treatment methods. OBJECTIVE: The intention of this study was to
      evaluate the intra-aneurysmal flow and flow reduction induced by flow diverters
      in a true-to-scale elastic aneurysm model, obtained from real patient data.
      METHODS: Based on the computed tomography angiography (CTA) data of a fusiform
      aneurysm of a 34 year old patient, an elastic silicon rubber model of the
      aneurysm was produced. A physiologic pulsatile flow was created with a
      circulatory experimental set-up, and a non-Newtonian perfusion fluid was used as
      a substitute for human blood. Hemodynamics were measured by LDA before and after
      flow diverter implantation. RESULTS: Implantation of a flow diverter device
      resulted in a reduction of intra-aneurysmal maximum flow velocities of 97.8% at
      the inflow zone, 89.1% in the dome and 89.3% at the outflow zone, when compared
      to the native model. A significant reduction of 94% in the mean intra-aneurysmal
      velocity was found. CONCLUSIONS: This promising methodology can optimize patient
      treatment and will correlate with computational simulations to evaluate their
      reliability.

PMID- 25777297
TI  - Nonlinear modeling was applied thoughtfully for risk prediction: the Prostate
      Biopsy Collaborative Group.
AB  - OBJECTIVES: We aimed to compare nonlinear modeling methods for handling
      continuous predictors for reproducibility and transportability of prediction
      models. STUDY DESIGN AND SETTING: We analyzed four cohorts of previously
      unscreened men who underwent prostate biopsy for diagnosing prostate cancer.
      Continuous predictors of prostate cancer included prostate-specific antigen and
      prostate volume. The logistic regression models included linear terms,
      logarithmic terms, fractional polynomials of degree one or two (FP1 and FP2), or
      restricted cubic splines (RCS) with three or five knots (RCS3 and RCS5). The
      resulting models were internally validated by bootstrap resampling and externally
      validated in the cohorts not used at model development. Performance was assessed
      with the area under the receiver operating characteristic curve (AUC) and the
      calibration component of the Brier score (CAL). RESULTS: At internal validation
      models with FP2 or RCS5 showed slightly better performance than the other models
      (typically 0.004 difference in AUC and 0.001 in CAL). At external validation
      models containing logarithms, FP1, or RCS3 showed better performance (differences
      0.01 and 0.002). CONCLUSION: Flexible nonlinear modeling methods led to better
      model performance at internal validation. However, when application of the model
      is intended across a wide range of settings, less flexible functions may be more
      appropriate to maximize external validity.

PMID- 25777300
TI  - Palladium-catalyzed highly efficient synthesis of functionalized indolizines via
      cross-coupling/cycloisomerization cascade.
AB  - An efficient Pd-catalyzed cross-coupling/cycloisomerization of 3-(2-pyridyl)
      propargyl carbonates with organoboronic acids has been developed, which provides
      a straightforward route for the synthesis of 1,3-disubstituted indolizines with a
      wide variety of substituents. The mechanistic study indicates that the reaction
      proceeds via formation of an allenyl pyridine intermediate through palladium
      catalyzed coupling reaction followed by cyclization. 

PMID- 25777301
TI  - IRF3 deficiency impacts granzyme B expression and maintenance of memory T cell
      function in response to viral infection.
AB  - The role of interferon regulatory factor 3 (IRF3) in the innate immune response
      to infection has been well studied. However, less is known about IRF3 signaling
      in shaping the adaptive T cell response. To determine the role of IRF3 in the
      generation and maintenance of effective anti-viral T cell responses, mice
      deficient in IRF3 were infected with a potentially persistent virus, Theiler's
      murine encephalomyelitis virus (TMEV) or with a model acute infection, influenza
      A virus (IAV). IRF3 was required to prevent TMEV persistence and induce robust
      TMEV specific effector T cell responses at the site of infection. This defect was
      more pronounced in the memory phase with an apparent lack of TMEV-specific memory
      T cells expressing granzyme B (GrB) in IRF3 deficient mice. In contrast, IRF3 had
      no effect on antigen specific T cell responses at the effector stage during IAV
      infection. However, memory T cell responses to IAV were also impaired in IRF3
      deficient mice. Furthermore, addition of cytokines during peptide restimulation
      could not restore GrB expression in IRF3 deficient memory T cells. Taken
      together, IRF3 plays an important role in the maintenance of effective anti-viral
      T cell memory responses. 

PMID- 25777302
TI  - Birth order and mortality: a population-based cohort study.
AB  - This study uses Swedish population register data to investigate the relationship
      between birth order and mortality at ages 30 to 69 for Swedish cohorts born
      between 1938 and 1960, using a within-family comparison. The main analyses are
      conducted with discrete-time survival analysis using a within-family comparison,
      and the estimates are adjusted for age, mother's age at the time of birth, and
      cohort. Focusing on sibships ranging in size from two to six, we find that
      mortality risk in adulthood increases with later birth order. The results show
      that the relative effect of birth order is greater among women than among men.
      This pattern is consistent for all the major causes of death but is particularly
      pronounced for mortality attributable to cancers of the respiratory system and to
      external causes. Further analyses in which we adjust for adult socioeconomic
      status and adult educational attainment suggest that social pathways only mediate
      the relationship between birth order and mortality risk in adulthood to a limited
      degree. 

PMID- 25777304
TI  - Keloid-derived keratinocytes acquire a fibroblast-like appearance and an enhanced
      invasive capacity in a hypoxic microenvironment in vitro.
AB  - A keloid scar is an overgrowth of dense fibrous tissue that develops around a
      wound. These scars are raised scars that spread beyong the margins of the
      orinigal wound to normal skin by invasion. Keloid tissue consists of both an
      epithelium and dermal fibroblasts. Recent studies have primarily focused on
      keloid fibroblasts; however, the precise role of keratinocytes in the invasion
      process of keloids remains to be identified. Hypoxia is a typical characteristic
      of keloid scars, as well as other solid tumors. The expression of the
      transcription factor, hypoxia-inducible factor-1alpha (HIF-1alpha), is mainly
      induced by hypoxia and is known for its ability to induce proliferative and
      transformative changes in cells; its expression has been shown to correlate with
      tumor invasion and metastasis. In the present study, we used
      immunohistochemistry, fluorescence staining and western blot analysis and
      demonstrated that HIF-1alpha was highly expressed in both the epithelial layer of
      keloid tissue specimens and in hypoxia-exposed keratinocytes, which suggested
      that the keloid keratinocytes underwent epithelial-to-mesenchymal transition
      (EMT) in vitro. The high expression of mesenchymal markers, such as as vimentin
      and fibronectin was confirmed, as well as the reduced expression of E-cadherin
      and zonula occludens-1 (ZO-1) during this process by detection at the protein and
      mRNA level. Moreover, siRNA targeting HIF-1alpha reversed the changes which had
      occurred in the morphology of the keratinocytes (cells had acquired a fibroblast
      like appearance) and suppressed the invasive ability of the keratinocytes. In
      conclusion, the present findings demonstrate that the hypoxia/HIF-1alpha
      microenvironment provides a favorable environment for keloid-derived
      keratinocytes to adopt a fibroblast-like appearance through EMT. This transition
      may be responsible for the enhanced capacity of keloid keratinocytes to invade,
      allowing the keloids to extend beyond the wound margin.

PMID- 25777305
TI  - Somatic mutations in myeloid cell leukemia-1 contribute to the pathogenesis of
      glioma by prolonging its half-life.
AB  - The identification of mutated genes in glioblastoma multiforme (GBM) is an
      essential step towards improving current understanding of the molecular mechanism
      underlying the disease and establishing novel targets for diagnostic and
      therapeutic purposes. The present study used direct sequencing to screen 20
      malignancy-associated genes, which have either been well described in the
      literature or observed multiple times in human cancer sequencing, in cancerous
      and normal control tissue samples from 20 patients with histologically confirmed
      GBM. The investigation identified five somatic non-synonymous coding mutations in
      four candidate genes, with two located in the proline, glutamic acid, serine,
      threonine-rich region of myeloid cell leukemia sequence 1 (Mcl)-1, (D155G and
      L174S). The sample pool was then expanded by sequencing Mcl-1 in a further 43
      patients with GBM and another somatic mutation in the same region, D155H, was
      identified. The subsequent functional investigation confirmed that these somatic
      mutations affected the degradation of Mcl-1, and the growth of glioma cells
      transfected with mutant plasmids was significantly accelerated compared with
      cells overexpressing wild-type Mcl-1. The mutational profiling of GBM in the
      present study revealed for the first time, to the best of our knowledge, several
      mutations in Mcl-1, and identified this gene as a novel therapeutic target for
      the treatment of GBM.

PMID- 25777303
TI  - Rationally designed molecular beacons for bioanalytical and biomedical
      applications.
AB  - Nucleic acids hold promise as biomolecules for future applications in biomedicine
      and biotechnology. Their well-defined structures and compositions afford unique
      chemical properties and biological functions. Moreover, the specificity of
      hydrogen-bonded Watson-Crick interactions allows the construction of nucleic acid
      sequences with multiple functions. In particular, the development of nucleic acid
      probes as essential molecular engineering tools will make a significant
      contribution to advancements in biosensing, bioimaging and therapy. The molecular
      beacon (MB), first conceptualized by Tyagi and Kramer in 1996, is an excellent
      example of a double-stranded nucleic acid (dsDNA) probe. Although inactive in the
      absence of a target, dsDNA probes can report the presence of a specific target
      through hybridization or a specific recognition-triggered change in conformation.
      MB probes are typically fluorescently labeled oligonucleotides that range from 25
      to 35 nucleotides (nt) in length, and their structure can be divided into three
      components: stem, loop and reporter. The intrinsic merit of MBs depends on
      predictable design, reproducibility of synthesis, simplicity of modification, and
      built-in signal transduction. Using resonance energy transfer (RET) for signal
      transduction, MBs are further endowed with increased sensitivity, rapid response
      and universality, making them ideal for chemical sensing, environmental
      monitoring and biological imaging, in contrast to other nucleic acid probes.
      Furthermore, integrating MBs with targeting ligands or molecular drugs can
      substantially support their in vivo applications in theranositics. In this
      review, we survey advances in bioanalytical and biomedical applications of
      rationally designed MBs, as they have evolved through the collaborative efforts
      of many researchers. We first discuss improvements to the three components of
      MBs: stem, loop and reporter. The current applications of MBs in biosensing,
      bioimaging and therapy will then be described. In particular, we emphasize recent
      progress in constructing MB-based biosensors in homogeneous solution or on solid
      surfaces. We expect that such rationally designed and functionalized MBs will
      open up new and exciting avenues for biological and medical research and
      applications. 

PMID- 25777306
TI  - Age-related macular degeneration in ethnically diverse Australia: Melbourne
      Collaborative Cohort Study.
AB  - PURPOSE: To determine and compare the prevalence of age-related macular
      degeneration (AMD) in older Australians of Anglo-Celtic and Southern European
      origin. METHODS: A total of 21,132 participants of the Melbourne Collaborative
      Cohort Study, aged 47-86 years, were assessed for AMD in 2003-2007 with non
      mydriatic fundus photography. Of these, 14% were born in Southern Europe (Greece,
      Italy or Malta), with the remaining 86% of Anglo-Celtic origin, born in
      Australia, the United Kingdom or New Zealand. RESULTS: Overall, 2694 participants
      (12.7%) had early stages of AMD, defined as either one or more drusen >= 125 MUm
      (with or without pigmentary abnormalities) or one or more drusen 63-124 MUm with
      pigmentary abnormalities in a 6000-MUm diameter grading grid, in the absence of
      late AMD in either eye. A total of 122 participants (0.6%) had late AMD, defined
      as either geographic atrophy or neovascular AMD. In logistic regression analysis,
      adjusted for age, sex, smoking, education and physical activity, Southern
      Europeans compared to Anglo-Celts had a higher prevalence of the early stages of
      AMD (odds ratio, OR, 1.15, 95% confidence interval, CI, 1.00-1.34), and lower
      prevalence of late AMD (OR 0.36, 95% CI 0.17-0.78). CONCLUSIONS: Australians of
      Southern European origin have a higher prevalence of the early stages of AMD and
      lower prevalence of late AMD compared to those of Anglo-Celtic origin. Although
      AMD prevalence in the older age group(s) of Southern Europeans could be
      underestimated due to disparity in participation rates, it is likely that both
      lifestyle and genetic factors play their parts in differential AMD prevalence in
      these ethnic groups.

PMID- 25777308
TI  - Seasonality and incidence of central retinal vein occlusion in Sweden: a 6-year
      study.
AB  - PURPOSE: To investigate seasonality in onset and incidence of central retinal
      vein occlusion (CRVO) in Stockholm, Sweden. METHODS: A retrospective consecutive
      population-based case series of patients presenting to the emergency department
      with CRVO from January 2008 through December 2013 at the St Erik Eye Hospital.
      Date, age at occurrence and sex were recorded in the study cohort. RESULTS: A
      total of 854 patients presented with CRVO during the study period. Peak CRVO
      onset occurred during the winter/spring period and was significantly higher than
      during the summer/autumn period. The number of patients presenting by season
      were: 166 (28.8%, 95% confidence interval, CI, 25.3-32.6%) in winter, 172 (29.9%,
      95% CI 26.3-33.7%) in spring, 131 (22.7%, 95% CI 19.5-26.3%) in summer, and 107
      (18.9%, 95% CI 15.6-22.0%) in autumn (p < 0.0002). There were more males,
      accounting for 53.9% of subjects (460/856; p = 0.029). Mean annual incidence of
      CRVO was 2/10,000 for persons aged over 40 years, increasing from 0.25/10,000 at
      45 years to 7/10,000 at 85 years (p < 0.001). CONCLUSIONS: The onset of CRVO in
      Stockholm, Sweden, had a significant seasonal pattern and most cases occurred
      during the winter-spring period. The highest incidence of CRVO was found in
      elderly people.

PMID- 25777307
TI  - Prospective study of plasma homocysteine level and risk of age-related macular
      degeneration in women.
AB  - PURPOSE: Prospective data to examine the association of homocysteine with age
      related macular degeneration (AMD) are limited. We examined the prospective
      relation of plasma homocysteine level and AMD in a large cohort of apparently
      healthy women. METHODS: We evaluated the relationship between baseline levels of
      plasma homocysteine and incident AMD among 27,479 female health professionals
      aged 40 years or older. Main outcome measures were total AMD, defined as self
      report documented by medical record evidence of an initial diagnosis after
      randomization, and visually significant AMD, defined as confirmed incident AMD
      with visual acuity 20/30 or worse attributable to this condition. RESULTS: During
      an average 10 years of follow-up, a total of 452 cases of AMD, including 182
      cases of visually significant AMD, were documented. Women in the highest versus
      lowest quartile of plasma homocysteine had modestly, but statistically non
      significant, increased risks of total AMD (hazard ratio, HR, 1.24, 95% confidence
      interval, CI, 0.95-1.63; p for trend 0.07) and visually significant AMD (HR 1.41,
      95% CI 0.92-2.17; p for trend 0.052) in age- and treatment-adjusted analyses.
      CONCLUSIONS: These prospective data from a large cohort of apparently healthy
      women do not support a strong role for homocysteine in AMD occurrence.

PMID- 25777309
TI  - Nigeria normative data for defining glaucoma in prevalence surveys.
AB  - PURPOSE: To determine normative values for defining glaucoma in cross-sectional
      surveys in Nigerian adults. METHODS: Multistage stratified cluster random
      sampling with probability-proportional-to-size procedures to select a nationally
      representative sample of 15,027 persons aged >= 40 years in 305 clusters across
      Nigeria. Systematic sampling of 1 in 7 participants gave 1759 who were examined
      in detail to construct a normative database. The normative subset was used to
      determine values for vertical cup/disc ratio (VCDR) and intraocular pressure
      (IOP) for glaucoma diagnosis according to the International Society of
      Geographical and Epidemiological Ophthalmology (ISGEO) criteria. Examinations
      included visual field testing by frequency doubling technology (FDT), Goldmann
      applanation tonometry, and optic disc image grading by Moorfields Eye Hospital
      Reading Centre. RESULTS: In the normative dataset, 1057/1759 persons (60.1%) had
      normal FDTs, and constituted the hypernormal. Of these, 851 had VCDR and 973 had
      IOP measurements taken in both eyes. For category 1 (structural and functional
      evidence of glaucoma), the 97.5th percentile VCDR was 0.7. For category 2
      (advanced structural damage with unproven visual field loss), the 99.5th
      percentile VCDR was 0.75. In addition, asymmetry in VCDR was 0.1 difference at
      the 97.5th percentile and 0.2 difference at the 99.5th percentile. Category 3
      criteria were used when the optic disc was not visible and field testing not
      possible; 99.5th percentile IOP is one criterion (28 mmHg). CONCLUSION: While
      these results do not differentiate between open-angle and angle-closure
      mechanisms, they can be applied to determine the prevalence of glaucoma in
      Nigeria and sub-Saharan African countries with similar sociodemographic
      characteristics.

PMID- 25777310
TI  - Determinants and characteristics of angle-closure disease in an elderly Chinese
      population.
AB  - PURPOSE: To determine factors associated with angle-closure disease, particularly
      in those with structural or functional damage to the eyes, in an elderly Chinese
      population. METHODS: A total of 460 individuals aged over 72 years were
      recruited. The association of angle-closure diseases, including primary angle
      closure suspect (PACS), primary angle-closure (PAC) and primary angle-closure
      glaucoma (PACG), with various systemic and ocular characteristics was evaluated
      using multivariate logistic regression analyses. RESULTS: Of 374 phakic subjects,
      199 (53.2%) had angle-closure disease, including 135 PACS, 46 PAC, and 18 PACG.
      The majority of those with untreated PACG (10/13, 76.9%) had presenting
      intraocular pressure (IOP) < 20 mmHg. Independent risk factors for angle-closure
      disease were lower Van Herick grading, shallower central anterior chamber depth
      (ACD), and higher post-mydriatic IOP (all p < 0.05). Central and peripheral ACD
      estimation correlated weakly, only 60.8% of angle-closure eyes had generalized
      narrowing of ACD as a Van Herick grading <= 2 and central ACD <= 2.83 mm. A
      criterion considering either central or peripheral ACD identified 91% of angle
      closure eyes, including all PACG. A higher post-mydriatic IOP was associated with
      a diagnosis of PAC or PACG among angle-closure eyes (p = 0.002). CONCLUSION: Both
      central and peripheral ACD should be evaluated and shallowing of either one
      should be an indication for gonioscopic examination to maximize detection of
      angle-closure disease in elderly Chinese persons. PAC and PACG were associated
      with higher post-mydriatic IOP than PACS, although subjects with PACG frequently
      presented with normal IOP.

PMID- 25777311
TI  - Sudden vision loss and cardiovascular risk factors in African Americans: the
      Jackson Heart Study.
AB  - PURPOSE: The prevalence and determinants of sudden vision loss (SVL) are unknown
      in African Americans (AAs). Since SVL can be cardiovascular disease (CVD)-related
      and CVD is highly prevalent in AAs, we examined the prevalence of and CVD factors
      related to self-reported SVL lasting 24 hours or longer in the cohort of AAs
      enrolled in the Jackson Heart Study (JHS). METHODS: The study population
      comprised 5301 participants enrolled from 2000-2004 in the metropolitan area of
      Jackson, MS, USA. All participants who responded to the question "Have you ever
      had any sudden loss of vision or blurring, lasting 24 hours or longer?" on the
      baseline stroke questionnaire were included in the study. We estimated the
      prevalence of SVL and used regression modeling to identify CVD factors
      independently related to SVL. RESULTS: A total of 5262 participants were
      included, of which 63% (3334/5262) were female. The prevalence of SVL was 3.6%
      (193/5262) overall (4.4% in females and 2.4% in males), and 8.7% (84/965) in
      patients with diabetes mellitus. Factors independently related to SVL included
      coronary heart disease (odds ratio, OR, 1.69, 95% confidence interval, CI, 1.12
      2.56), cerebrovascular disease (OR 2.81, 95% CI 1.76-4.47), diabetes (OR 2.85,
      95% CI 2.05-3.94), hypertension (OR 1.64, 95% CI 1.09-2.45), female sex (OR 1.82,
      95% CI 1.24-2.67), and income less than US$50,000 (OR 2.05, 95% CI 1.28-3.30).
      CONCLUSIONS: In this cohort of AAs, self-reported SVL lasting 24 hours or longer
      was highly prevalent in women and those with diabetes and was independently
      related to sex, CVD, CVD risk factors and household income.

PMID- 25777312
TI  - Ophthalmic manifestations in children and young adults with Down syndrome and
      congenital heart defects.
AB  - PURPOSE: To investigate whether different types of ocular manifestations are
      associated with congenital heart disease (CHD) in a large Caucasian population of
      children and young adults with Down syndrome (DS). METHODS: Population-based,
      case-control study which included 185 subjects with DS (mean age 13.2 +/- 7.9
      years), who reported presence or absence of CHD; DS with CHD group (51 subjects,
      mean age 10.6 +/- 5.6 years) and DS without CHD (134 subjects, mean age 14.2 +/-
      8.4 years). RESULTS: In our sample with DS and CHD, strabismus was found in 15
      subjects (29.4%), nystagmus in 1 (2.0%), epiblepharon in 21 (41.2%) and
      Brushfield spots in 15 (31.3%). In the DS without CHD group, strabismus was found
      in 38 participants (28.4%), nystagmus in 13 (9.7%), epiblepharon in 31 (23.5%)
      and Brushfield spots in 21 (16.0%). Only the variables epiblepharon and presence
      of Brushfield spots differed significantly between the two groups (p = 0.02 and p
      = 0.03, respectively). Hyperopia was present in 26 participants (53.1%) in the DS
      with CHD group, and in 65 (57.0%) in the DS without CHD group. Oblique
      astigmatism was present in 25 (52.1%) in the DS with CHD group and in 61 (53.5%)
      in the DS without CHD group. CONCLUSIONS: Frequencies of DS participants
      presenting with strabismus, nystagmus, hyperopia and oblique astigmatism were not
      statistically different between those with CHD and those without CHD in this
      sample. Further studies are needed to confirm if there are associations between
      the presence of Brushfield spots or epiblepharon and CHD in patients with DS.

PMID- 25777313
TI  - Prevalence and associated factors of pinguecula in a rural population in
      Shanghai, Eastern China.
AB  - PURPOSE: To determine the prevalence and associated factors of pinguecula in a
      rural Chinese population aged >= 50 years in Eastern China. METHODS: This cross
      sectional, population-based survey included an age-stratified random sample of
      1108 residents living in Lvxiang Town of Jinshan District. Participants were
      requested to complete a comprehensive questionnaire to collect demographic data,
      history of systemic diseases and lifestyle details. The presence of pinguecula on
      slit lamp examination was recorded. The prevalence of pinguecula and its
      associated factors were investigated by logistic regression models. RESULTS:
      Among 1108 eligible subjects, 959 participated in the study, with an average age
      of 65.1 +/- 9.2 years (range 50-89 years). The overall age-adjusted prevalence of
      pinguecula in this population was 75.57% (95% confidence interval 71.79-79.35%).
      Logistic regression analysis revealed that age (p = 0.002) and working outdoors
      (daily sunlight exposure >= 2 hours; p = 0.001) were independent risk factors for
      pinguecula. In addition, sex, education level, alcohol intake, smoking and
      decreased tear break-up time did not have associations with the development of
      pinguecula after adjusting for age and outdoor work occupations. CONCLUSIONS: The
      prevalence of pinguecula was 75.57% in this Chinese population aged >= 50 years
      from a coastal rural area of Shanghai, Eastern China, which was higher than the
      majority of previous findings. Age and working outdoors were independent risk
      factors for pinguecula.

PMID- 25777314
TI  - Accuracy of the International Classification of Diseases, Ninth Revision,
      Clinical Modification (ICD-9-CM) as a research tool for identification of
      patients with uveitis and scleritis.
AB  - PURPOSE: To report on the accuracy of the International Classification of
      Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) codes for identifying
      patients with polymyalgia rheumatica (PMR) and concurrent noninfectious
      inflammatory ocular conditions in a large healthcare organization database.
      METHODS: Queries for patients with PMR and uveitis or scleritis were executed in
      two general teaching hospitals' databases. Patients with ocular infections or
      other rheumatologic conditions were excluded. Patients with PMR and ocular
      inflammation were identified, and medical records were reviewed to confirm
      accuracy. RESULTS: The query identified 10,697 patients with the ICD-9-CM code
      for PMR and 4154 patients with the codes for noninfectious inflammatory ocular
      conditions. The number of patients with both PMR and noninfectious uveitis or
      scleritis by ICD-9-CM codes was 66. On detailed review of the charts of these 66
      patients, 31 (47%) had a clinical diagnosis of PMR, 43 (65%) had noninfectious
      uveitis or scleritis, and only 20 (30%) had PMR with concurrent noninfectious
      uveitis or scleritis confirmed based on clinical notes. CONCLUSIONS: While the
      use of ICD-9-CM codes has been validated for medical research of common diseases,
      our results suggest that ICD-9-CM codes may be of limited value for
      epidemiological investigations of diseases which can be more difficult to
      diagnose. The ICD-9-CM codes for rarer diseases (PMR, uveitis and scleritis) did
      not reflect the true clinical problem in a large proportion of our patients. This
      is particularly true when coding is performed by physicians outside the area of
      specialty of the diagnosis.

PMID- 25777315
TI  - Determination of visual impairment associated with alcohol consumption.

PMID- 25777316
TI  - Author reply: To PMID 25271895.

PMID- 25777318
TI  - Oxygenation mediating the valence density-of-states and work function of Ti(0001)
      skin.
AB  - Consistency between density function theory calculations and photoelectron
      spectroscopy observations confirmed predictions based on the framework of bond
      band-barrier (3B) correlation notation [Sun, Prog. Mater. Sci., 2003, 48, 521
      685] that an oxygen adsorbate interacts with Ti(0001) skin atoms to form a
      tetrahedron with creation of four valence density-of-state features: O-Ti bonding
      electron pairs, O nonbonding lone pairs, Ti electronic holes, and Ti antibonding
      dipoles. Formation of the dipoles lowers the work function of the Ti(0001) skin
      and electron-hole generation turns the metallic Ti(0001) into the semiconductive
      O-Ti(0001). Findings confirm the universality of the 3B correlation in
      understanding the dynamics of oxygen chemisorption and the associated valence
      electrons involved in the process of oxidation. 

PMID- 25777317
TI  - Factors associated with early childhood caries incidence among high caries-risk
      children.
AB  - OBJECTIVES: To assess the relationships between different behavioral factors and
      Early Childhood Caries (ECC) in African-American pre-school children. METHODS:
      Ninety-six African-American children aged 3-22 months old at baseline were
      recruited from a high caries risk, non-fluoridated African-American community in
      Uniontown, Alabama. The children had dental examinations annually following World
      Health Organization (WHO) criteria at mean ages 1.1, 2.0, 3.1 and 4.0 years. All
      children received fluoride varnish application at each study visit. Parents
      provided oral hygiene and dietary information semiannually by completing
      questionnaires. Area-under-the-curve (AUC) with the trapezoidal rule was used to
      summarize longitudinal exposure data. Bivariate and multivariable relationships
      between ECC incidence and behavioral risk factors were assessed using logistic
      regression and negative binomial modeling for dichotomous and count dependent
      variables, respectively, with the independent variables defined at age 1, age 3
      and as the AUC. RESULTS: Greater frequency of toothbrushing and greater AUC
      composite of daily frequency of consumption of 100% juices were associated with
      lower incidence of dental caries (P-values = 0.01 and 0.049, ORs = 0.34 and 0.37,
      respectively). Greater AUC of daily frequency of consumption of sweetened foods
      and history of a previous visit to a dentist by age 3 were associated with
      greater incidence of ECC (ORs = 9.22 and 4.57, P-values = 0.002 and 0.03,
      respectively). CONCLUSION: For these children living in a non-fluoridated
      community, more frequent consumption of sweetened food, less frequent consumption
      of 100% juice, less frequent toothbrushing, and reporting a previous visit to a
      dentist were significantly associated with greater ECC incidence.

PMID- 25777319
TI  - Glasgow prognostic score predicts prognosis for cancer patients in palliative
      settings: a subanalysis of the Japan-prognostic assessment tools validation (J
      ProVal) study.
AB  - PURPOSE: The Glasgow prognostic score (GPS), which uses C-reactive protein and
      albumin levels, is a good predictor of prognosis in cancer patients undergoing
      anti-tumor therapy. The objective of this study was to investigate the
      correlation between GPS and survival among cancer patients in palliative
      settings, as findings in such populations have not been well described. METHODS:
      This was a subanalysis of a multicenter, prospective, cohort study in patients
      who were adults, diagnosed with advanced cancer, and first referred to palliative
      care service in Japan. Patients who were not receiving anti-tumor therapy and who
      had undergone laboratory examinations were eligible. Clinical features were
      analyzed to investigate prognostic factors. RESULTS: A total of 1160 patients
      were enrolled (41.6 % female; median age, 72 years). The independent predictors
      were Eastern Cooperative Oncology Group performance status (ECOG PS) score of 4
      (hazard ratio (HR), 1.54), liver metastasis (HR, 1.21), dyspnea (HR, 1.35), edema
      (HR, 1.25), prognostic performance index (HR, 1.56), neutrophil-lymphocyte ratio
      (HR, 1.43), and GPS of 2 (HR, 1.36). The sensitivity and specificity for 3-week
      prognosis of a GPS of 2 were 0.879 and 0.410. Median survival time with GPS of 0,
      1, and 2 was 58 days (95 % confidence interval, 48-81), 43 days (37-50), and 21
      days (19-24), respectively (log-rank test, p < 0.001). CONCLUSION: The GPS was a
      good prognostic indicator for cancer patients in palliative settings.

PMID- 25777320
TI  - New insights into the diverse electronic phases of a novel vanadium dioxide
      polymorph: a terahertz spectroscopy study.
AB  - A remarkable feature of vanadium dioxide is that it can be synthesized in a
      number of polymorphs. The conductivity mechanism in the metastable layered
      polymorph VO2(B) thin films has been investigated by terahertz time-domain
      spectroscopy (THz-TDS). In VO2(B), a critical temperature of 240 K marks the
      appearance of a non-zero Drude term in the observed complex conductivity,
      indicating the evolution from a pure insulating state towards a metallic state.
      In contrast, the THz conductivity of the well-known VO2(M1) is well fitted only
      by a modification of the Drude model to include backscattering. We also
      identified two different THz conductivity regimes separated by temperature in
      these two polymorphs. The electronic phase diagram is constructed, revealing that
      the width and onset of the metal-insulator transition in the B phase develop
      differently from the M1 phase.

PMID- 25777321
TI  - Liver transplantation for hepatocellular carcinoma: analysis of factors
      predicting outcome in 1074 patients in OPTN Region 5.
AB  - Previous studies on loco-regional therapy (LRT) and alpha-fetoprotein (AFP) in
      predicting outcome after liver transplant (LT) for hepatocellular carcinoma (HCC)
      have shown inconsistent results. We analyzed the OPTN database in Region 5 from
      January 2004 to January 2009 and performed univariate and multivariate analysis
      of 11 pre-transplant recipient and donor variables in 1074 patients with HCC
      meeting Milan criteria to detect association with post-LT tumor recurrence or
      mortality. Mean waitlist time was 438 d. The 1- and 5-yr post-LT survival was
      91.1% and 71.1%, respectively. In multivariate analysis, AFP before LT was the
      only predictor of HCC recurrence. The association between AFP and HCC recurrence
      was observed only in the subgroup receiving LRT but not in the subgroup without
      LRT. Predictors of mortality in multivariate analysis were HCC recurrence, Donor
      Risk Index, last AFP before LT, and MELD score. AFP before LT was the strongest
      predictor of post-transplant HCC recurrence or death in multivariate analysis. In
      conclusion, in Region 5 with prolonged waitlist time, high AFP was the only pre
      transplant variable predicting post-transplant tumor recurrence and mortality for
      HCC meeting Milan criteria. Our results also supported the importance of the
      effects of LRT on AFP in predicting prognosis.

PMID- 25777322
TI  - Interaction between voriconazole and flucloxacillin during treatment of
      disseminated Scedosporium apiospermum infection.

PMID- 25777323
TI  - Letter to the Editor: Heinz bodies and erythrophagocytosis in the peripheral
      blood of loggerhead sea turtles.

PMID- 25777324
TI  - Initial experience of dual maintenance immunosuppression with steroid withdrawal
      in vascular composite tissue allotransplantation.
AB  - Current immunosuppression in VCA is largely based on the experience in solid
      organ transplantation. It remains unclear if steroids can be reduced safely in
      VCA recipients. We report on five VCA recipients who were weaned off maintenance
      steroids after a median of 2 months (mean: 4.8 months, range 2-12 months).
      Patients were kept subsequently on a low dose, dual maintenance consisting of
      tacrolimus and mycophenolate mofetil/mycophenloic acid with a mean follow-up of
      43.6 months (median = 40 months, range 34-64 months). Early and late acute
      rejections responded well to temporarily augmented maintenance, topical
      immunosuppression, and/or steroid bolus treatment. One late steroid-resistant
      acute rejection required treatment with thymoglobulin. All patients have been
      gradually weaned off steroids subsequent to the treatment of acute rejections.
      Low levels of tacrolimus (<5 ng/mL) appeared as a risk for acute rejections.
      Although further experience and a cautious approach are warranted, dual-steroid
      free maintenance immunosuppression appears feasible in a series of five VCA
      recipients. 

PMID- 25777325
TI  - Coassembly of nanorods and nanospheres in suspensions and in stratified films.
AB  - The entropically driven coassembly of nanorods (cellulose nanocrystals, CNCs) and
      nanospheres (dye-labeled spherical latex nanoparticles, NPs) was studied in
      aqueous suspensions and in solid films. In mixed CNC-latex suspensions, phase
      separation into an isotropic latex-NP-rich and a chiral nematic CNC-rich phase
      took place; the latter contained a significant amount of latex NPs. Drying the
      mixed suspension resulted in CNC-latex films with planar disordered layers of
      latex NPs, which alternated with chiral nematic CNC-rich regions. In addition,
      fluorescent latex NPs were embedded in the chiral nematic domains. The stratified
      morphology of the films, together with a random distribution of latex NPs in the
      anisotropic phase, led to the films having close-to-uniform fluorescence,
      birefringence, and circular dichroism properties. 

PMID- 25777326
TI  - Molecular dynamics study of ionic liquids complexation within beta-cyclodextrins.
AB  - We have studied 1:1 inclusion complexes of two imidazole-based ionic liquids
      within beta-cyclodextrin: 1-dodecyl-3-methylimidazolium and 1-butyl-3
      methylimidazolium. By means of an adaptive biasing force scheme, we obtained the
      free energy profile along two different pathways, differing in the orientations
      of the head-to-tail vector with respect to the primary-secondary rim axis.
      Regarding 1-dodecyl-3-methylimidazolium, we found one minimum energy structure
      for each pathway, in which the hydrophobic tail remains embedded within the
      cyclodextrin, while the headgroup lies ~11-12 A from one of the rims; the
      structure where the polar head lies near the primary rim is the most stable. The
      analysis of the free energy of encapsulation of 1-butyl-3-methylimidazolium shows
      two minima for each insertion pathway, each of them associated with
      configurations where the imidazolium head lies close to one of the polar rims. As
      such, the most stable structure corresponds to one where the hydrophobic tail
      lies embedded within the cyclodextrin, while its head is localized near the
      secondary rim. The results are interpreted in terms of a simple model which
      captures the essential features that control the encapsulation process. A
      comparison with available experimental data is presented.

PMID- 25777327
TI  - Accelerometer output and its association with energy expenditure during manual
      wheelchair propulsion.
AB  - STUDY DESIGN: This is an experimental design. OBJECTIVES: This study examined the
      association between rates of energy expenditure (that is, oxygen consumption
      (VO2)) and accelerometer counts (that is, vector magnitude (VM)) across a range
      of speeds during manual wheelchair propulsion on a motor-driven treadmill. Such
      an association allows for the generation of cutoff points for quantifying the
      time spent in moderate-to-vigorous physical activity (MVPA) during manual
      wheelchair propulsion. SETTING: The study was conducted in the University
      Laboratory. METHODS: Twenty-four manual wheelchair users completed a 6-min period
      of seated rest and three 6-min periods of manual wheelchair propulsion on a motor
      driven wheelchair treadmill. The 6-min periods of wheelchair propulsion
      corresponded with three treadmill speeds (1.5, 3.0 and 4.5 mph) that elicited a
      range of physical activity intensities. Participants wore a portable metabolic
      unit and accelerometers on both wrists. Primary outcome measures included steady
      state VO2 and VM, and the strength of association between VO2 and VM was based on
      the multiple correlation and squared multiple correlation coefficients from
      linear regression analyses. RESULTS: Strong linear associations were established
      between VO2 and VM for the left (R=0.93+/-0.44; R2=0.87+/-0.19), right (R=0.95+/
      0.37; R2=0.90+/-0.14) and combined (R=0.94+/-0.38; R2=0.88+/-0.15)
      accelerometers. The linear relationship between VO2 and VM for the left, right
      and combined wrists yielded cutoff points for MVPA of 3659 +/-1302, 3630+/-1403
      and 3644+/-1339 counts min(-1), respectively. CONCLUSION: We provide cutoff
      points based on the linear association between energy expenditure and
      accelerometer counts for estimating time spent in MVPA during manual wheelchair
      propulsion using wrist-worn accelerometry. The similarity across wrist location
      permits flexibility in selecting a location for wrist accelerometry placement.

PMID- 25777328
TI  - Accommodation of wheelchair-reliant individuals by community fitness facilities.
AB  - BACKGROUND: Adhering to the recommended healthy physical activity guidelines can
      be difficult for individuals with spinal cord injury (SCI), stroke or other
      paralytic conditions. Ordinary community structures such as curbs, stairs and
      narrow passageways can present as major obstacles for individuals who are reliant
      on wheelchairs. The Americans with Disabilities Act (ADA) of 1990 mandates that
      public facilities, including community fitness centers, should be accessible to
      everyone. STUDY DESIGN: Analysis of compliance of the ADA and accommodation of
      wheelchair-reliant individuals. OBJECTIVES: To determine the level of compliance
      with ADA and the degree of accommodation of wheelchair-reliant individuals.
      SETTING: Community fitness centers in the Hattiesburg, Mississippi metropolitan
      area. METHODS: Ten fitness centers consented to unfettered access for evaluation
      of ADA compliance and accommodation of wheelchair-reliant individuals using an 82
      item checklist. RESULTS: All surveyed facilities were found to be partially
      compliant, with none of the facilities being 100% compliant. The areas of least
      compliance were access to and free movement around exercise equipment and full
      access to restrooms. Beyond ADA accessibility, only 20% of the participating
      facilities provided suitable adaptive equipment, and no facilities employed staff
      trained for the special needs of those with paralytic conditions. CONCLUSION:
      Beyond mandated physical accessibility, accommodation of individuals who are
      reliant on wheelchairs because of SCI or other paralytic conditions was found to
      be lacking. It remains important for health-care professionals and other advocacy
      groups to stress the need for inclusion and accommodation of individuals with
      disabilities to community fitness facilities allowing wellness needs to be met.

PMID- 25777329
TI  - Wheelchair users' perceived exertion during typical mobility activities.
AB  - STUDY DESIGN: Each participant performed a series of wheelchair exercises
      equivalent in intensity to minimal functional speed (1 m s(-1)), functional
      walking speed (1.3 m s(-1)), a relatively challenging speed (1.6 m s(-1)) and a
      self-selected speed. Each participant also completed a graded exercise test (GXT)
      to volitional exhaustion (VO2peak). OBJECTIVES: The purpose of this study was (1)
      to assess the physical capacity of wheelchair users as they undertake typical
      mobility activities and (2) to investigate how closely the components of a
      differentiated model of perceived exertion mirror wheelchair users' own
      perception of exertion. METHODS: Eleven (eight males and three females) spinal
      cord-injured or congenitally impaired wheelchair-dependent participants
      volunteered for the study. Differentiated ratings of perceived exertion (RPE_arm
      and RPE_respiration) and oxygen uptake (VO2) and heart rate were recorded during
      each exercise. RESULTS: The mean comfortable speed at which the participants
      propelled their own wheelchairs on the wheelchair ergometer was 1.1+/-0.2 m s(
      1). Speeds of 1 m s(-1) and 1.3 m s(-1) are typical of everyday functional
      propulsion. The corresponding RPE_respiration and RPE_arm ranged from 7 to 13 on
      the Borg scale; the %VO2peak measured in these trials ranged from 37 to 80%
      VO2peak. For propulsion intensities used in the present study-low, moderate, high
      and graded exercise intensity-no difference could be observed between
      RPE_respiration and RPE_arm. There were no significant differences between
      RPE_arm and RPE_respiration at the termination of the GXT. CONCLUSION: The
      current study showed potential for the use of RPE to assess and monitor daily
      wheelchair propulsion intensity in individuals with paraplegia.

PMID- 25777330
TI  - Pain medication misuse among participants with spinal cord injury.
AB  - STUDY DESIGN: Self-reported survey. OBJECTIVE: Our purpose was to identify the
      predictors of pain medication misuse (PMM) among participants with spinal cord
      injury (SCI). SETTING: A medical university in the southeastern United States.
      METHODS: A total of 919 adults with impairment from traumatic SCI of at least 1
      year duration, who reported at least one painful condition and were taking
      prescription medication to treat pain, were included in this study. PMM was
      measured by the Pain Medication Questionnaire (PMQ). RESULTS: The average PMQ
      score was 19.7, with 25.8% of participants scoring at or above the cutoff of 25,
      which is indicative of PMM. A three-stage logistic regression analysis was
      conducted by sequentially adding three sets of predictors to the equation: (1)
      demographic and injury characteristics; (2) pain characteristics and (3)
      frequency of pain medication use. Age and education level were protective of PMM,
      whereas pain intensity, pain interference and pain medication use were risk
      factors. Number of painful days was not significant in the final model.
      CONCLUSION: PMM must be of concern after SCI, given its high prevalence among
      those with at least one painful condition and its relationship with pain
      indicators.

PMID- 25777331
TI  - Early MRI finding in adult spinal cord injury without radiologic abnormalities
      does not correlate with the neurological outcome: a retrospective study.
AB  - STUDY DESIGN: Adult spinal cord injury without radiologic abnormalities (SCIWORA)
      is evidenced to be underreported. Some abnormalities that were not present on
      computed tomography (CT) were identified on magnetic resonance imaging (MRI), but
      the diagnostic reliability of early MRI remains considerable disagreement.
      OBJECTIVE: The present study was retrospectively designed to assess a potential
      correlation between clinical and imaging findings in adults experiencing SCIWORA.
      SETTING: A total of 2964 adult patients (age >18 or older) with acute cervical
      spine injury presented to the single institution between January 2009 and June
      2014. METHODS: Fifty-nine patients with SCIWORA were included in the study.
      Initial MRI findings at admission were analyzed, and a 6-month follow-up was
      performed. RESULTS: On admission, complete spinal cord injury was found in 32
      patients, incomplete spinal cord injury in 20 patients and central cord syndrome
      in seven patients. MRI findings showed varying degrees of degenerative or
      spondylotic changes in 45% of the patients (n=27). The cord contusion was shown
      in 12 patients, cord edema in 7, cord hemorrhage in 2 and ligamentum flavum
      bulging in 4 patients. In all, two of these patients had no positive findings on
      the initial MRI, but presented with positive abnormalities on repeat MRI 72 h
      after trauma. At discharge, most of the patients presented with complete
      remission, but some of the patients presented with partial remission. After 6
      months, all patients significantly improved, and only two patients did not show
      full recovery. CONCLUSIONS: Early use of MRI added little in the determination of
      stability of the cervical spine in the presence of a negative CT. Our study
      suggested that the neurological outcome did not correlate with early MRI
      findings.

PMID- 25777332
TI  - Hindrance of spasticity after spinal cord injury.

PMID- 25777333
TI  - An intermediate respiratory care unit for spinal cord-injured patients. A
      retrospective study.
AB  - OBJECTIVES: Patients with cervical spinal cord injury (SCI) may need prolonged
      mechanical ventilation (MV) and a long stay in the Intensive Care Unit. An
      intermediate respiratory care unit (IRCU) can shorten that stay, optimizing
      hospital resources. The aim of our work has been to evaluate the activity of such
      a unit in our hospital. METHODS: This is a descriptive retrospective study based
      on the data of patients with SCI and respiratory failure discharged from our IRCU
      between 1 July 2010 and 28 February 2013. RESULTS: We have analysed data from 146
      patients with SCI, adding up to 228 admissions (68 first admissions and 160
      readmissions due to complications or scheduled review visits). Sixty-three out of
      the 68 newly admitted patients survived their first admission (92.6%). Length of
      hospitalization was 195.6+/-110.4 days, 22 were admitted to monitor their
      respiratory status and 46 were on MV on admission. Of these, 26 (38.2%) were
      admitted to attempt weaning from the respirator and 20 (29.4%) to enter a
      programme of permanent respiratory support. Weaning was successful in 23 out of
      26 patients (88.4%), the process taking 47.2+/-49.3 days. Forty of them (58.8%)
      were discharged to their home. CONCLUSIONS: An IRCU can manage a substantial
      number of severe SCI patients who need MV, and an important number of them can be
      weaned from the respirator. It may also achieve a good success rate in the
      integration of MV-dependent patients within family and society.

PMID- 25777334
TI  - Functional hindrance due to spasticity in individuals with spinal cord injury
      during inpatient rehabilitation and 1 year thereafter.
AB  - STUDY DESIGN: Prospective cohort study. OBJECTIVE: To assess functional hindrance
      due to spasticity during inpatient rehabilitation and 1 year thereafter in
      individuals with spinal cord injury (SCI) and to determine factors that influence
      the hindrance. SETTING: Eight specialized rehabilitation centres in the
      Netherlands. METHODS: A total of 203 patients with recent SCI rated the hindrance
      they perceived due to spasticity in daily living at the start of active
      rehabilitation (t1), 3 months later (t2), at discharge (t3) and 1 year after
      discharge (t4). Hindrance was dichotomized into absent or negligible and present.
      Multilevel regression analyses were performed to determine the course of
      functional hindrance due to spasticity and its associations with possible
      determinants-namely, age, gender, cause, lesion level, motor completeness,
      spasticity and anti-spasticity medication. RESULTS: The percentage of individuals
      that indicated functional hindrance due to spasticity ranged from 54 to 62% over
      time and did not change significantly over time (Deltat3t1 odds ratio (OR)=0.85,
      P=0.44; Deltat3t2 OR=1.20, P=0.41; Deltat3t4 OR=0.91, P=0.67). The percentage of
      individuals who experienced a lot of hindrance due to spasticity during specific
      activities ranged from 4 to 27%. The odds for experiencing functional hindrance
      due to spasticity were significantly higher for individuals with tetraplegia
      (OR=2.17, P=0.0001), more severe spasticity (OR=5.51, P<0.0001) and for those
      using anti-spasticity medication (OR=4.18, P<0.0001). CONCLUSION: Functional
      hindrance due to spasticity occurred in the majority of persons with SCI and did
      not change significantly during inpatient rehabilitation and 1 year thereafter.
      Factors that influence hindrance were determined.

PMID- 25777336
TI  - Editor's note.

PMID- 25777335
TI  - Is sport practice a risk factor for shoulder injuries in tetraplegic individuals?
AB  - STUDY DESIGN: A retrospective cohort. OBJECTIVES: To report the incidence rates
      of shoulder injuries diagnosed with magnetic resonance imaging (MRI) in
      tetraplegic athletes and sedentary tetraplegic individuals. To evaluate whether
      sport practice increases the risk of shoulder injuries in tetraplegic
      individuals. SETTING: Campinas, Sao Paulo, Brazil. METHODS: Ten tetraplegic
      athletes with traumatic spinal cord injury were selected among quad rugby
      athletes and had both the shoulders evaluated by MRI. They were compared with 10
      sedentary tetraplegic individuals who were submitted to the same radiological
      protocol. RESULTS: All athletes were male with a mean age of 32.1 years (range 25
      44 years, s.d.=6.44). Time since injury ranged from 6 to 17 years, with a mean
      value of 9.7 years and s.d. of 3.1 years. All sedentary individuals were male
      with a mean age of 35.9 years (range 22-47 years, s.d.=8.36). Statistical
      analysis showed a protective effect of sport in the development of shoulder
      injuries, with a weak correlation for infraspinatus and subscapularis
      tendinopathy (P=0.09 and P=0.08, respectively) and muscle atrophy (P=0.08). There
      was a strong correlation for acromioclavicular joint (ACJ) and labrum injuries
      (P=0.04), with sedentary individuals at a higher risk for these injuries.
      CONCLUSION: Tetraplegic athletes and sedentary individuals have a high incidence
      of supraspinatus tendinosis, bursitis and ACJ degeneration. Statistical analysis
      showed that there is a possible protective effect of sport in the development of
      shoulder injuries. Weak evidence was encountered for infraspinatus and
      subscapularis tendinopathy and muscle atrophy (P=0.09, P=0.08 and P=0.08,
      respectively). Strong evidence with P=0.04 suggests that sedentary tetraplegic
      individuals are at a greater risk for ACJ and labrum injuries.

PMID- 25777338
TI  - Monolithic metal oxide transistors.
AB  - We devised a simple transparent metal oxide thin film transistor architecture
      composed of only two component materials, an amorphous metal oxide and ion gel
      gate dielectric, which could be entirely assembled using room-temperature
      processes on a plastic substrate. The geometry cleverly takes advantage of the
      unique characteristics of the two components. An oxide layer is metallized upon
      exposure to plasma, leading to the formation of a monolithic source-channel-drain
      oxide layer, and the ion gel gate dielectric is used to gate the transistor
      channel effectively at low voltages through a coplanar gate. We confirmed that
      the method is generally applicable to a variety of sol-gel-processed amorphous
      metal oxides, including indium oxide, indium zinc oxide, and indium gallium zinc
      oxide. An inverter NOT logic device was assembled using the resulting devices as
      a proof of concept demonstration of the applicability of the devices to logic
      circuits. The favorable characteristics of these devices, including (i) the
      simplicity of the device structure with only two components, (ii) the benign
      fabrication processes at room temperature, (iii) the low-voltage operation under
      2 V, and (iv) the excellent and stable electrical performances, together support
      the application of these devices to low-cost portable gadgets, i.e., cheap
      electronics. 

PMID- 25777337
TI  - Non-cirrhotic thrombocytopenic patients with hepatitis C virus: Characteristics
      and outcome of antiviral therapy.
AB  - BACKGROUND AND AIM: Thrombocytopenia is frequently observed in patients with
      chronic hepatitis C virus (HCV) infection and cirrhosis, although it can also be
      observed in patients without cirrhosis by a virus-mediated phenomenon. This study
      assessed the prevalence, characteristics, and outcomes of antiviral therapy in
      patients with chronic HCV infection and thrombocytopenia not associated with
      cirrhosis. METHODS: The study included 1268 patients with HCV infection and
      thrombocytopenia enrolled in the phase 3 ENABLE studies that assessed the impact
      of eltrombopag on achieving a sustained virologic response to pegylated
      interferon and ribavirin. The study population was subdivided according to
      baseline FibroSURE test results into patients with non-cirrhosis (FibroSURE <
      0.4) and cirrhosis-related (FibroSURE >= 0.75) thrombocytopenia. RESULTS:
      Compared with patients with cirrhosis-related thrombocytopenia (n = 995; 78.5%),
      non-cirrhotic patients with thrombocytopenia (n = 59; 4.6%) were younger (mean
      age [95% confidence interval (CI)]: 43.9 [40.7-47.2] vs 52.7 [52.2-53.3] years; P
      < 0.0001), predominantly female (64% [51-76] vs 30% [27-33]; P < 0.0001), and
      less frequently had a Model for End-Stage Liver Disease score >= 10 (24% [14-37]
      vs 45% [42-49]; P = 0.0012), low albumin levels (<= 35 g/L; 2% [0-9] vs 32% [29
      35]; P < 0.0001), and prevalence of diabetes mellitus (3% [0-12] vs 21% [19-24];
      P = 0.0005). The sustained virologic response rate was higher in non-cirrhotic
      patients with thrombocytopenia (46% [95% CI, 33-59] vs 16% [14-18]; P < 0.0001).
      CONCLUSIONS: Patients with thrombocytopenia associated with HCV who have lower
      FibroSURE test results may have better preserved liver function and higher
      sustained virologic response rates than patients with cirrhosis.

PMID- 25777339
TI  - Archaeosomes: an excellent carrier for drug and cell delivery.
AB  - Archaeosomes as liposomes made with one or more ether lipids that are unique to
      the domain of Archaeobacteria, found in Archaea constitute a novel family of
      liposome. Achaean-type lipids consist of archaeol (diether) and/or caldarchaeol
      (tetraether) core structures. Archaeosomes can be produced using standard
      procedures (hydrated film submitted to sonication, extrusion and detergent
      dialysis) at any temperature in the physiological range or lower, therefore
      making it possible to encapsulate thermally stable compounds. Various
      physiological as well as environmental factors affect its stability. Archaeosomes
      are widely used as drug delivery systems for cancer vaccines, Chagas disease,
      proteins and peptides, gene delivery, antigen delivery and delivery of natural
      antioxidant compounds. In this review article, our major aim was to explore the
      applications of this new carrier system in pharmaceutical field.

PMID- 25777340
TI  - SWEETWISE: developing a multi-professional approach to diabetes mellitus.
AB  - The formation of a local joint professional network (LJPN) in Northamptonshire
      has led to a joint Continuing professional development initiative and an audit
      project to determine the take up of annual health checks by patients with
      diabetes mellitus with dentists, optometrists, pharmacists as well as the usual
      check with the General Medical Practice team. The findings showed that a
      significant number of patients (29-50%) do not access available dental, optometry
      and pharmacy advice. Better collaboration between the professions has the
      potential to improve health outcomes in diabetes mellitus and other areas where
      lifestyle modification reduces adverse health risks. A patient advice card
      (SWEETWISE) was developed by the group and could be used to help educate patients
      and health professionals. 

PMID- 25777341
TI  - Curcuma zedoaria (Berg.) Rosc. essential oil and paclitaxel synergistically
      enhance the apoptosis of SKOV3 cells.
AB  - Curcuma zedoaria (Berg.) Rosc. essential oil (CZEO) is the major component of
      Curcuma zedoaria (Berg.) Rosc., a traditional medicine with antitumor activity.
      Paclitaxel (PTX) is a first-line chemotherapeutic agent used to treat patients
      with ovarian cancer. These compounds directly target nuclear DNA, in order to
      suppress or inhibit tumor cell growth. The present study aimed to determine the
      synergistic antitumor effects of CZEO and PTX on the SKOV3 human ovarian cancer
      cell line. SKOV3 cells were treated with CZEO, PTX or a combination of the two
      and cell viability was detected using cell counting kit-8. In addition, flow
      cytometry was used to determined cell apoptosis as well as for cell cycle
      analysis. The morpho-logical changes of apoptosis were assessed using Hoechst
      33342 staining and the expression levels of apoptotic pathway proteins, including
      caspase-3 and poly (ADP-ribose) polymerase (PARP), were quantified using western
      blot analysis. The cell viability assay indicated that either of these compounds
      alone or in combination suppressed the growth of SKOV3 cells. Furthermore, flow
      cytometric analysis indicated that treatment with a combination of CZEO and PTX
      resulted in increased inhibition of proliferation and induction of apoptosis of
      SKOV3 cells, as compared with treatment with either of the compounds alone. In
      addition, the protein expression levels of caspase-3 were increased following
      treatment with a combination of CZEO and PTX. The results of the present study
      suggested that CZEO and PTX synergistically enhanced the inhibition of SKOV3
      proliferation, and the possible underlying mechanism may be the induction of cell
      apoptosis and cell cycle arrest. This therefore indicated that PTX supplemented
      with CZEO may be an effective treatment strategy to decrease the dose and
      toxicity of PTX.

PMID- 25777342
TI  - Habitat fragmentation alters the properties of a host-parasite network: rodents
      and their helminths in South-East Asia.
AB  - 1. While the effects of deforestation and habitat fragmentation on parasite
      prevalence or richness are well investigated, host-parasite networks are still
      understudied despite their importance in understanding the mechanisms of these
      major disturbances. Because fragmentation may negatively impact species
      occupancy, abundance and co-occurrence, we predict a link between spatiotemporal
      changes in habitat and the architecture of host-parasite networks. 2. For this,
      we used an extensive data set on 16 rodent species and 29 helminth species from
      seven localities of South-East Asia. We analysed the effects of rapid
      deforestation on connectance and modularity of helminth-parasite networks. We
      estimated both the degree of fragmentation and the rate of deforestation through
      the development of land uses and their changes through the last 20 to 30 years in
      order to take into account the dynamics of habitat fragmentation in our
      statistical analyses. 3. We found that rapid fragmentation does not affect
      helminth species richness per se but impacts host-parasite interactions as the
      rodent-helminth network becomes less connected and more modular. 4. Our results
      suggest that parasite sharing among host species may become more difficult to
      maintain with the increase of habitat disturbance.

PMID- 25777343
TI  - Identification of cytotoxic T lymphocyte epitopes in dengue virus serotype 1.
AB  - Dengue virus (DENV) has a serious and growing impact on global health and the
      exact role of DENV-specific CD8(+) T-cells in DENV infection is still uncertain.
      In the present study, SYFPEITHI algorithm was used to screen the amino acid
      sequence of Dengue virus serotype 1 (DENV-1) for potential epitopes, and seven
      putative HLA-A*1101-restricted and five putative HLA-A*2402-restricted epitopes
      conserved in hundreds of DENV-1 strains were synthesized. The binding affinity of
      these epitope candidates to corresponding HLA molecules was evaluated using
      competitive peptide-binding assay. The immunogenicity and specificity of peptides
      were further tested in HLA-A*1101 transgenic mice, HLA-A*2402 transgenic mice and
      peripheral blood mononuclear cells (PBMCs) of patients infected with DENV-1.
      Percentage inhibition (PI) values calculated in competitive peptide-binding assay
      showed that six peptides (E39-47 PTLDIELLK, NS5(505-513) GVEGEGLHK, NS2b(15-23)
      SILLSSLLK, NS5(561-569) ALLATSIFK, NS3(99-107) AVEPGKNPK, and NS4b(159-167)
      VVYDAKFEK) could bind to HLA-A*1101 molecule with high affinity and five peptides
      (NS3472-480 QYIYMGQPL, NS4a40-48 AYRHAMEEL, NS5(880-888) DYMTSMKRF, NS3(548-556)
      SYKVASEGF, and NS3(22-30) IYRILQRGL) have a high affinity for HLA-A*2402
      molecule. Enzyme-linked immunospot (ELISPOT) results indicated that these high
      affinity peptides were recognized by splenocytes of DENV-1-infected transgenic
      mice and high-affinity peptide-immunized transgenic mice displayed high levels of
      peptide-specific IFN-gamma-secreting cells. In addition, both peptide-pulsed
      splenocytes and DENV-1-infected splenic monocytes were efficiently killed by
      these peptide-specific cytotoxic T lymphocytes. Finally, except NS2b(15-23), 10
      high-affinity peptides were recognized by PBMCs of patients infected with DENV-1.
      These identified epitopes would contribute to the understanding of the function
      of DENV-specific CD8(+) T-cells.

PMID- 25777344
TI  - Concentrations of highly sensitive cardiac troponin-I predict poor cardiovascular
      outcomes and adverse remodeling in chronic heart failure.
AB  - Highly sensitive troponin (hsTn) assays may predict cardiovascular (CV) events
      and left ventricular (LV) remodeling in patients with heart failure (HF). In this
      study, 99 subjects with LV systolic dysfunction (LVSD) were followed 10 +/- 3
      months with serial measurement of hsTnI by a novel method. hsTnI was detectable
      in all subjects and was above the 99th percentile of a normal population in 56.7
      %. Supramedian baseline hsTnI concentration was associated with higher-risk
      clinical features and shorter time-to-first event (p = 0.008). Across serial
      measurements, more time spent <= 10.9 pg/mL was associated with a lower CV event
      rate after adjustment (odds ratio (OR) = 0.81; p = 0.008); rising hsTnI also
      predicted progressive LV remodeling. In conclusion, hsTnI detected significant
      myocardial necrosis in a majority of patients with chronic HF due to LVSD and
      when measured serially, provided independent risk information for poor CV
      outcomes and deleterious LV remodeling.

PMID- 25777345
TI  - Phase II study of sorafenib and bortezomib for first-line treatment of metastatic
      or unresectable renal cell carcinoma.
AB  - BACKGROUND: Sorafenib is an orally active multikinase inhibitor, and bortezomib
      is a proteasome inhibitor that affects multiple signaling pathways. Sorafenib has
      clinical activity in renal cell carcinoma (RCC), whereas bortezomib has
      demonstrated activity against RCC cell lines in vitro, with in vitro studies
      showing synergism between the two agents in the induction of apoptosis in
      neoplastic cell lines. In this phase II study, we explored the efficacy and
      toxicity of this regimen. METHODS: Adult patients with cytologically confirmed
      clear cell RCC with no prior chemotherapy, Zubrod performance status of 0-1,
      serum creatinine <1.5 mg/dL, and normal liver function tests were treated with
      sorafenib 200 mg orally b.i.d. with bortezomib 1 mg/m(2) intravenously on days 1,
      4, 8, and 11 every 21 days. Treatment was continued until disease progression or
      unacceptable toxicity. The primary objective was median progression-free survival
      (PFS) of at least 70 weeks. RESULTS: Seventeen patients were enrolled between
      April 2011 and January 2013. Median age was 62 years (range: 44-75 years). Four
      of 17 patients had known brain metastasis on enrollment. Median number of cycles
      was 4 (range: 1 to >=45). No patient had complete response, 1 had partial
      response, 12 had stable disease, and 4 had progressive disease (response rate of
      6%; 95% confidence interval: 0%-29%) with treatment. Median PFS was 13.7 weeks,
      and median overall survival was 110 weeks. The study was halted for futility.
      CONCLUSION: The combination of sorafenib and bortezomib was well tolerated;
      however, response rate and PFS were comparable to sorafenib monotherapy. This
      regimen is not recommended for further development.

PMID- 25777346
TI  - The Prostate Cancer DREAM Challenge: A Community-Wide Effort to Use Open Clinical
      Trial Data for the Quantitative Prediction of Outcomes in Metastatic Prostate
      Cancer.

PMID- 25777347
TI  - A phase IIb trial assessing the addition of disulfiram to chemotherapy for the
      treatment of metastatic non-small cell lung cancer.
AB  - BACKGROUND: Disulfiram, an alcohol aversion agent, has been in use for >50 years.
      Numerous authors have reported an anticancer effect of this drug in vitro and in
      mouse models. More recently, several reports have claimed that disulfiram also
      possesses anti-stem cell activity. We set out to obtain initial data regarding
      the safety of combining this drug with chemotherapy and the possible
      effectiveness of disulfiram in a combination regimen in non-small cell lung
      cancer (NSCLC). METHODS: This phase II, multicenter, randomized, double-blinded
      study assessed the safety and efficacy of adding of disulfiram to cisplatin and
      vinorelbine for six cycles. Newly diagnosed NSCLC patients were recruited.
      Patients with either stage IV or what was considered at the time "wet IIIb"
      (since 2009, these patients have been considered stage IV) were recruited. The
      patients were treated with only chemotherapy, and none were treated with either
      surgery or chemoradiation. Disulfiram was administered at a dose of 40 mg three
      times daily. RESULTS: Forty patients were treated for more than two cycles, half
      with and half without disulfiram, which was well tolerated. An increase in
      survival was noted for the experimental group (10 vs. 7.1 months). Interestingly,
      there were only two long-term survivors, both in the disulfiram group.
      CONCLUSION: The addition of disulfiram to a combination regimen of cisplatin and
      vinorelbine was well tolerated and appeared to prolong survival in patients with
      newly diagnosed non-small cell lung cancer. The results from this small study
      seem encouraging enough for assessment in larger trials. Disulfiram is an
      inexpensive and safe drug; if its addition to chemotherapy could be shown to
      prolong survival, an effective regimen could be established and used widely, even
      in resource-poor countries.

PMID- 25777349
TI  - Allelic ratio of KRAS mutations in pancreatic cancer.

PMID- 25777348
TI  - BRCA1 and BRCA2 mutations in ethnic Lebanese Arab women with high hereditary risk
      breast cancer.
AB  - PURPOSE: Breast cancer is the most common malignancy among women in Lebanon and
      in Arab countries, with 50% of cases presenting before the age of 50 years.
      METHODS: Between 2009 and 2012, 250 Lebanese women with breast cancer who were
      considered to be at high risk of carrying BRCA1 or BRCA2 mutations because of
      presentation at young age and/or positive family history (FH) of breast or
      ovarian cancer were recruited. Clinical data were analyzed statistically. Coding
      exons and intron-exon boundaries of BRCA1 and BRCA2 were sequenced from
      peripheral blood DNA. All patients were tested for BRCA1 rearrangements using
      multiplex ligation-dependent probe amplification (MLPA). BRCA2 MLPA was done in
      selected cases. RESULTS: Overall, 14 of 250 patients (5.6%) carried a deleterious
      BRCA mutation (7 BRCA1, 7 BRCA2) and 31 (12.4%) carried a variant of uncertain
      significance. Eight of 74 patients (10.8%) aged <=40 years with positive FH and
      only 1 of 74 patients (1.4%) aged <=40 years without FH had a mutated BRCA. Four
      of 75 patients (5.3%) aged 41-50 years with FH had a deleterious mutation. Only 1
      of 27 patients aged >50 years at diagnosis had a BRCA mutation. All seven
      patients with BRCA1 mutations had grade 3 infiltrating ductal carcinoma and
      triple-negative breast cancer. Nine BRCA1 and 17 BRCA2 common haplotypes were
      observed. CONCLUSION: Prevalence of deleterious BRCA mutations is lower than
      expected and does not support the hypothesis that BRCA mutations alone cause the
      observed high percentage of breast cancer in young women of Lebanese and Arab
      descent. Studies to search for other genetic mutations are recommended.

PMID- 25777350
TI  - Reflections on caring for the international uninsured patient.

PMID- 25777355
TI  - Consciousness wanted, attention found: Reasons for the advantage of the left
      visual field in identifying T2 among rapidly presented series.
AB  - Everyday experience suggests that people are equally aware of events in both hemi
      fields. However, when two streams of stimuli are rapidly presented left and right
      containing two targets, the second target is better identified in the left than
      in the right visual field. This might be considered evidence for a right
      hemisphere advantage in generating conscious percepts. However, this putative
      asymmetry of conscious perception cannot be measured independently of
      participants' access to their conscious percepts, and there is actually evidence
      from split-brain patients for the reverse, left-hemisphere advantage in having
      access to conscious percepts. Several other topics were studied in search of the
      responsible mechanism, among others: Mutual inhibition of hemispheres,
      cooperation of hemispheres in perceiving midline stimuli, and asymmetries in
      processing various perceptual inputs. Directing attention by salient cues turned
      out to be one of the few mechanisms capable of modifying the left visual-field
      advantage in this paradigm. Thus, this left visual-field advantage is best
      explained by the notion of a right-hemisphere advantage in directing attention to
      salient events. Dovetailing with the pathological asymmetries of attention after
      right-hemisphere lesions and with asymmetries of brain activation when healthy
      participants shift their attention, the present results extend that body of
      evidence by demonstrating unusually large and reliable behavioral asymmetries for
      attention-directing processes in healthy participants. 

PMID- 25777356
TI  - Variable phenotypes in Greig cephalopolysyndactyly sydrome (GCPS) and their
      relevance to plastic surgery.
AB  - BACKGROUND: Greig cephalopolysyndactyly syndrome (GCPS) is an uncommon entity
      characterised by polysyndactyly and craniofacial features. The syndrome is not
      defined by classic signs. Instead there is a high variability in phenotypes
      observed. This is due to the large number of different mutations in the glioma
      associated oncogene 3 (GLI3) that can give rise to the syndrome. We present a
      case series of five un-related individuals with GCPS treated in our hand surgery
      unit with different phenotype presentations of GCPS. CONCLUSION: An awareness of
      the diversity in phenotypes is important for diagnosis and early referral for
      genetic confirmation and counselling.

PMID- 25777357
TI  - Impact of adiposity, age, sex and maternal feeding practices on eating in the
      absence of hunger and caloric compensation in preschool children.
AB  - BACKGROUND/OBJECTIVES: Between the ages of 3 and 5 years, children may become
      less responsive to internal cues of satiation and more responsive to external
      cues, which may induce overeating and lead to weight gain. This study aimed to
      compare eating in the absence of hunger (EAH) and caloric compensation in 3- to 6
      year-old children, and to relate the measurements with children's adiposity, age,
      sex and maternal feeding practices. METHODS: According to a within-subject three
      sequential condition design, food intake in children (n=236) was measured at
      lunch during three sessions, once a week. The same meal (565 kcal) was offered at
      each session. The first session (control) was only composed of the meal. Thirty
      minutes before the second meal, children were offered an energy preload (137
      kcal; caloric compensation condition). Ten minutes after the third meal, children
      were exposed to a post-meal snack (430 kcal; EAH condition). Individual caloric
      compensation score (COMPX) and EAH score were calculated. Maternal
      characteristics were measured by questionnaire. Child anthropometrics were
      measured by a medical doctor. RESULTS: On average, children compensated 52+/-4%
      of the energy preload and ate 24+/-1% of the energy provided by their meal in the
      absence of hunger. COMPX and EAH score were not correlated and did not vary with
      children's adiposity or age. EAH score was higher in boys (P=0.006). Maternal use
      of food as reward was associated with higher EAH score (P=0.01) but greater COMPX
      (P=0.005). CONCLUSIONS: As early as the age of 3 years children did not fully
      compensate the energy brought by a snack and ate in the absence of hunger.
      Parents should be advised to avoid these situations where overeating may occur
      and to limit the use of food as reward.

PMID- 25777358
TI  - Breast cancer-related lymphedema and sexual experiences: a mixed-method
      comparison study.
AB  - OBJECTIVE: Up to 40% of breast cancer survivors develop lymphedema, a chronic and
      sometimes disabling condition that manifests as abnormal swelling of the effected
      arm or hand or upper chest areas. Although the effects of lymphedema on quality
      of life have been well established, less well documented are the sexual
      experiences of breast cancer survivors with lymphedema. This study is the first
      to compare the sexual experiences of women with (n = 243) and without breast
      cancer-related lymphedema (n = 109). METHODS: A mixed-method design was used to
      explore both quantitatively and qualitatively the impact of lymphedema on
      participants' sexual experiences. RESULTS: Participants with breast cancer
      related lymphedema reported struggles with compression garments and sexual
      intimacy, negative feelings involving the breast and arm, and feelings of
      decreased sexual desire. CONCLUSIONS: Recommendations for healthcare
      professionals, social workers, and marriage and family therapists are offered
      with the aim of assisting women with breast cancer-related lymphedema and their
      sexual partners.

PMID- 25777360
TI  - ITCH modulates SIRT6 and SREBP2 to influence lipid metabolism and atherosclerosis
      in ApoE null mice.
AB  - Atherosclerosis is a chronic inflammatory disease characterized by the
      infiltration of pro-inflammatory macrophages into a lipid-laden plaque. ITCH is
      an E3 ubiquitin ligase that has been shown to polarize macrophages to an anti
      inflammatory phenotype. We therefore investigated the effect of ITCH deficiency
      on the development of atherosclerosis. ApoE-/-ITCH-/- mice fed a western diet for
      12 weeks showed increased circulating M2 macrophages together with a reduction in
      plaque formation. Bone marrow transplantation recreated the haemopoietic
      phenotype of increased circulating M2 macrophages but failed to affect plaque
      development. Intriguingly, the loss of ITCH lead to a reduction in circulating
      cholesterol levels through interference with nuclear SREBP2 clearance. This
      resulted in increased LDL reuptake through upregulation of LDL receptor
      expression. Furthermore, ApoE-/-ITCH-/- mice exhibit reduced hepatic steatosis,
      increased mitochondrial oxidative capacity and an increased reliance on fatty
      acids as energy source. We found that ITCH ubiquitinates SIRT6, leading to its
      breakdown, and thus promoting hepatic lipid infiltration through reduced fatty
      acid oxidation. The E3 Ubiquitin Ligase ITCH modulates lipid metabolism impacting
      on atherosclerosis progression independently from effects on myeloid cells
      polarization through control of SIRT6 and SREBP2 ubiquitination. Thus, modulation
      of ITCH may provide a target for the treatment of hypercholesterolemia and
      hyperlipidemia. 

PMID- 25777363
TI  - Cannabis in cancer care.
AB  - Cannabis has been used in medicine for thousands of years prior to achieving its
      current illicit substance status. Cannabinoids, the active components of Cannabis
      sativa, mimic the effects of the endogenous cannabinoids (endocannabinoids),
      activating specific cannabinoid receptors, particularly CB1 found predominantly
      in the central nervous system and CB2 found predominantly in cells involved with
      immune function. Delta-9-tetrahydrocannabinol, the main bioactive cannabinoid in
      the plant, has been available as a prescription medication approved for treatment
      of cancer chemotherapy-induced nausea and vomiting and anorexia associated with
      the AIDS wasting syndrome. Cannabinoids may be of benefit in the treatment of
      cancer-related pain, possibly synergistic with opioid analgesics. Cannabinoids
      have been shown to be of benefit in the treatment of HIV-related peripheral
      neuropathy, suggesting that they may be worthy of study in patients with other
      neuropathic symptoms. Cannabinoids have a favorable drug safety profile, but
      their medical use is predominantly limited by their psychoactive effects and
      their limited bioavailability. 

PMID- 25777362
TI  - A platform for rapid generation of single and multiplexed reporters in human iPSC
      lines.
AB  - Induced pluripotent stem cells (iPSC) are important tools for drug discovery
      assays and toxicology screens. In this manuscript, we design high efficiency
      TALEN and ZFN to target two safe harbor sites on chromosome 13 and 19 in a widely
      available and well-characterized integration-free iPSC line. We show that these
      sites can be targeted in multiple iPSC lines to generate reporter systems while
      retaining pluripotent characteristics. We extend this concept to making lineage
      reporters using a C-terminal targeting strategy to endogenous genes that express
      in a lineage-specific fashion. Furthermore, we demonstrate that we can develop a
      master cell line strategy and then use a Cre-recombinase induced cassette
      exchange strategy to rapidly exchange reporter cassettes to develop new reporter
      lines in the same isogenic background at high efficiency. Equally important we
      show that this recombination strategy allows targeting at progenitor cell stages,
      further increasing the utility of the platform system. The results in concert
      provide a novel platform for rapidly developing custom single or dual reporter
      systems for screening assays. 

PMID- 25777364
TI  - Ti(IV)-catalyzed cascade synthesis of tetrahydrofuro[3,2-d]oxazole from arene-1,4
      diones.
AB  - A tetrahydrofuro[3,2-d]oxazole scaffold was synthesized efficiently and
      stereoselectively. The tandem ionic hydrogenation, ketalization, and
      intramolecular cyclization of arene-1,4-diones with a combination of TiCl4/Et3SiH
      give facile access to tetrahydrofuro[3,2-d]oxazole derivatives in good yields at
      room temperature. 

PMID- 25777365
TI  - Aerosol-Assisted Heteroassembly of Oxide Nanocrystals and Carbon Nanotubes into
      3D Mesoporous Composites for High-Rate Electrochemical Energy Storage.
AB  - Nanostructured composites built from ordinary building units have attracted much
      attention because of their collective properties for critical applications.
      Herein, we have demonstrated the heteroassembly of carbon nanotubes and oxide
      nanocrystals using an aerosol spray method to prepare nanostructured mesoporous
      composites for electrochemical energy storage. The designed composite
      architectures show high conductivity and hierarchically structured mesopores,
      which achieve rapid electron and ion transport in electrodes. Therefore, as
      synthesized carbon nanotube/TiO2 electrodes exhibit high rate performance through
      rapid Li(+) intercalation, making them suitable for ultrafast energy storage
      devices. Moreover, the synthesis process provides a broadly applicable method to
      achieve the heteroassembly of vast low-dimensional building blocks for many
      important applications. 

PMID- 25777366
TI  - Predicting postoperative complications of inguinal lymph node dissection for
      penile cancer in an international multicentre cohort.
AB  - OBJECTIVES: To assess the potential complications associated with inguinal lymph
      node dissection (ILND) across international tertiary care referral centres, and
      to determine the prognostic factors that best predict the development of these
      complications. MATERIALS AND METHODS: A retrospective chart review was conducted
      across four international cancer centres. The study population of 327 patients
      underwent diagnostic/therapeutic ILND. The endpoint was the overall incidence of
      complications and their respective severity (major/minor). The Clavien-Dindo
      classification system was used to standardize the reporting of complications.
      RESULTS: A total of 181 patients (55.4%) had a postoperative complication, with
      minor complications in 119 cases (65.7%) and major in 62 (34.3%). The total
      number of lymph nodes removed was an independent predictor of experiencing any
      complication, while the median number of lymph nodes removed was an independent
      predictor of major complications. The American Joint Committee on Cancer stage
      was an independent predictor of all wound infections, while the patient's age,
      ILND with Sartorius flap transposition, and surgery performed before the year
      2008 were independent predictors of major wound infections. CONCLUSIONS: This is
      the largest report of complication rates after ILND for squamous cell carcinoma
      of the penis and it shows that the majority of complications associated with ILND
      are minor and resolve without prolonged morbidity. Variables pertaining to the
      extent of disease burden have been found to be prognostic of increased
      postoperative morbidity.

PMID- 25777367
TI  - Salt-induced adaptation of a dynamic combinatorial library of pseudopeptidic
      macrocycles: unraveling the electrostatic effects in mixed aqueous media.
AB  - Dynamic combinatorial libraries are powerful systems for studying adaptive
      behaviors and relationships, as models of more complex molecular networks. With
      this aim, we set up a chemically diverse dynamic library of pseudopeptidic
      macrocycles containing amino-acid side chains with differently charged residues
      (negative, positive, and neutral). The responsive ability of this complex library
      upon the increase of the ionic strength has been thoroughly studied. The families
      of the macrocyclic members concentrating charges of the same sign showed a large
      increase in its proportion as the ionic strength increases, whereas those with
      residues of opposite charges showed the reverse behavior. This observation
      suggested an electrostatic shielding effect of the salt within the library of
      macrocycles. The top-down deconvolution of the library allowed us to obtain the
      fundamental thermodynamic information connecting the library members (exchange
      equilibrium constants), as well as to parameterize the adaptation to the external
      stimulus. We also visualized the physicochemical driving forces for the process
      by structural analysis using NMR spectroscopy and molecular modeling. This
      knowledge permitted the full understanding of the whole dynamic library and also
      the de novo design of dynamic chemical systems with tailored co-adaptive
      relationships, containing competing or cooperating species. This study highlights
      the utility of dynamic combinatorial libraries in the emerging field of systems
      chemistry. 

PMID- 25777368
TI  - Alcohol dehydrogenase 3 contributes to the protection of liver from nonalcoholic
      steatohepatitis.
AB  - Nutritional steatohepatitis is closely associated with dysregulation of lipid
      metabolism and oxidative stress control. ADH3 is a highly conserved bifunctional
      enzyme involved in formaldehyde detoxification and termination of nitric oxide
      signaling. Formaldehyde and nitric oxide are nonenzymatically conjugated with
      glutathione, which is regenerated after ADH3 metabolizes the conjugates. To
      clarify roles of ADH3 in nutritional liver diseases, we placed Adh3-null mice on
      a methionine- and choline-deficient (MCD) diet. The Adh3-null mice developed
      steatohepatitis more rapidly than wild-type mice, indicating that ADH3 protects
      liver from nutritional steatohepatitis. NRF2, which is a key regulator of
      cytoprotective genes against oxidative stress, was activated in the Adh3-null
      mice with liver damage. In the absence of NRF2, the Adh3 disruption caused severe
      steatohepatitis by the MCD diet feeding accompanied by significant decrease in
      glutathione, suggesting cooperative function between ADH3 and NRF2 in the
      maintenance of cellular glutathione level for cytoprotection. Conversely, with
      enhanced NRF2 activity, the Adh3 disruption did not cause steatohepatitis but
      induced steatosis, suggesting that perturbation of lipid metabolism in ADH3
      deficiency is not compensated by NRF2. Thus, ADH3 protects liver from steatosis
      by supporting normal lipid metabolism and prevents progression of steatosis into
      steatohepatitis by maintaining the cellular glutathione level. 

PMID- 25777369
TI  - Fumonisins B1, B2 and B3 in corn products, wheat flour and corn oil marketed in
      Shandong province of China.
AB  - In this study a total of 522 samples were collected from Shandong province of
      China in 2014 and analysed for the occurrence of fumonisin B1 (FB1), FB2 and FB3
      by isotope dilution ultrahigh performance liquid chromatography-tandem mass
      spectrometry. Fumonisins were detected in 98.1% of the corn products, with the
      average total level of 369.2 MUg kg(-1). The individual average values of FB1,
      FB2 and FB3 in corn products were 268.3, 53.7 and 47.2 MUg kg(-1), respectively.
      The simultaneous occurrence of FB1, FB2 and FB3 was observed in 76.7% of the corn
      products. Especially, the results demonstrated that the difference in the
      contamination levels for fumonisins in these three types of corn products was
      apparent. In addition, 6.2% of the wheat flour samples were contaminated with
      FB1, with concentrations ranging from 0.3 to 34.6 ug kg(-1). No FB2 or FB3 was
      detected in wheat flour. In corn oil samples no fumonisins were detected.

PMID- 25777420
TI  - The association of alcohol consumption with mammographic density in a multiethnic
      urban population.
AB  - BACKGROUND: Alcohol consumption is associated with higher breast cancer risk.
      While studies suggest a modest association between alcohol intake and
      mammographic density, few studies have examined the association in racial/ethnic
      minority populations. METHODS: We assessed dense breast area and total breast
      area from digitized film mammograms in an urban cohort of African American (42%),
      African Caribbean (22%), white (22%), and Hispanic Caribbean (9%) women (n = 189,
      ages 40-61). We examined the association between alcohol intake and mammographic
      density (percent density and dense area). We used linear regression to examine
      mean differences in mammographic density across alcohol intake categories. We
      considered confounding by age, body mass index (BMI), hormone contraceptive use,
      family history of breast cancer, menopausal status, smoking status, nativity,
      race/ethnicity, age at first birth, and parity. RESULTS: Fifty percent currently
      consumed alcohol. Women who consumed >7 servings/week of alcohol, but not those
      consuming <=7 servings/week, had higher percent density compared to nondrinkers
      after full adjustments (servings/week >7 beta = 8.2, 95% Confidence Interval (CI)
      1.8, 14.6; <=7 beta = -0.5, 95% CI -3.7, 2.8). There was a positive association
      between high alcohol intake and dense area after full adjustments (servings/week
      >7 beta = 5.8, 95% CI -2.7, 14.2; <=7 beta = -0.1, 95% CI -4.4, 4.2). We did not
      observe race/ethnicity modification of the association between alcohol intake and
      percent density. In women with a BMI of <25 kg/m(2), drinkers consuming >7
      servings/week of alcohol had a = 17% increase in percent density compared to
      nondrinkers (95% CI 5.4, 29.0) and there was no association in women with a BMI
      >= 25 kg/m(2) (BMI >= 25-30 kg/m(2) > 7 beta = 5.1, 95% CI -8.5, 18.7 and BMI >
      30 kg/m(2) > 7 beta = 0.5, 95% CI -6.5, 7.5) after adjusting for age and BMI
      (continuous). CONCLUSION: In a racially/ethnically diverse cohort, women who
      consumed >7 servings/week of alcohol, especially those with a BMI < 25 kg/m(2),
      had higher percent density.

PMID- 25777421
TI  - Impact of comorbidities and use of common medications on cancer and non-cancer
      specific survival in esophageal carcinoma.
AB  - BACKGROUND: Chronic comorbidities and some of the commonly-used medications are
      thought to affect cancer patients' outcomes, but their relative impact on
      esophageal carcinoma (EC) has not been well studied. The purpose of the study was
      to identify the chronic comorbidities and/or commonly-used medications that
      impact EC patient survival. METHODS: A total of 1174 EC patients treated with
      chemoradiotherapy (CRT) with or without surgery in one institution from 1998 to
      2012 were retrospectively included. Seven kinds of frequently occurring chronic
      comorbidities and 18 types of regularly-taken medications were obtained from
      medical records. Since it is expected prognostic factors have different effects
      between surgery patients and non-surgery patients, the impact value of all
      variables and the corresponding interactions with surgery on survival were
      evaluated in Cox proportional hazards regression model. Overall mortality, EC
      specific mortality and non EC-specific mortality were endpoints. RESULTS: We
      found that atrial fibrillation was the only comorbidity that showed a significant
      impact on non-EC specific survival for all patients (HR 1.72, P = 0.03), whereas
      hypothyroidism was the only comorbidity that was evaluated as an independent
      predictive factor for overall survival (OS) (HR 0.59, P = 0.02) and EC-specific
      survival (HR 0.62, P = 0.05), but this association was seen only in the non
      surgical patients. No other medications were found to have a significant impact
      for OS, EC-specific survival or non-EC specific survival in multivariable
      analysis. CONCLUSIONS: Our data indicate that certain comorbidities rather than
      medication use affect EC-specific survival or non EC-specific survival in EC
      patients treated with CRT with or without surgery. Comorbidity information may
      better guide individual treatment in EC.

PMID- 25777422
TI  - The association between human papillomavirus 16 and esophageal cancer in Chinese
      population: a meta-analysis.
AB  - BACKGROUND: The role of human papillomavirus (HPV) in the development of
      esophageal cancer remains controversial. Our study aims to test the association
      between HPV 16 infection and esophageal cancer in China, providing useful
      information on this unclear association in Chinese population. METHODS: Studies
      on HPV infection and esophageal cancer were identified. A random-effects model
      was used to calculate the odds ratios (ORs) and corresponding 95% confidence
      intervals (CIs) comparing cases with controls. RESULTS: A total of 1442
      esophageal cancer cases and 1602 controls from 10 included studies were evaluated
      to estimate the association between HPV 16 infection and esophageal cancer risk.
      The ORs for each case-control studies ranged from 3.65 (95% CI: 2.17, 6.13) to
      15.44 (95% CI: 3.42, 69.70). The pooled estimates for OR was 6.36 (95% CI: 4.46,
      9.07). In sensitivity analysis, the estimates for OR ranged from 5.92 (95% CI:
      4.08, 8.60) to 6.97 (95% CI: 4.89, 9.93). CONCLUSIONS: This study indicates that
      HPV-16 infection may be a risk factor for esophageal cancer among Chinese
      population, supporting an etiological role of HPV16 in this malignancy. Results
      in this study may have important implications for esophageal cancer prevention
      and treatment in China.

PMID- 25777460
TI  - Benzyl Alcohol: A novel treatment for acetaminophen overdose?

PMID- 25777461
TI  - Patterns of Reproductive Isolation in Eucalyptus-A Phylogenetic Perspective.
AB  - We assess phylogenetic patterns of hybridization in the speciose, ecologically
      and economically important genus Eucalyptus, in order to better understand the
      evolution of reproductive isolation. Eucalyptus globulus pollen was applied to 99
      eucalypt species, mainly from the large commercially important subgenus,
      Symphyomyrtus. In the 64 species that produce seeds, hybrid compatibility was
      assessed at two stages, hybrid-production (at approximately 1 month) and hybrid
      survival (at 9 months), and compared with phylogenies based on 8,350 genome-wide
      DArT (diversity arrays technology) markers. Model fitting was used to assess the
      relationship between compatibility and genetic distance, and whether or not the
      strength of incompatibility "snowballs" with divergence. There was a decline in
      compatibility with increasing genetic distance between species. Hybridization was
      common within two closely related clades (one including E. globulus), but rare
      between E. globulus and species in two phylogenetically distant clades. Of three
      alternative models tested (linear, slowdown, and snowball), we found consistent
      support for a snowball model, indicating that the strength of incompatibility
      accelerates relative to genetic distance. Although we can only speculate about
      the genetic basis of this pattern, it is consistent with a Dobzhansky-Muller
      model prediction that incompatibilities should snowball with divergence due to
      negative epistasis. Different rates of compatibility decline in the hybrid
      production and hybrid-survival measures suggest that early-acting postmating
      barriers developed first and are stronger than later-acting barriers. We
      estimated that complete reproductive isolation can take up to 21-31 My in
      Eucalyptus. Practical implications for hybrid eucalypt breeding and genetic risk
      assessment in Australia are discussed. 

PMID- 25777462
TI  - A Wide Complex Left Bundle Branch Block Tachycardia in a Patient with Complete
      Right Bundle Branch Block: What is the Mechanism?

PMID- 25777463
TI  - Association of Objectively Measured Physical Activity and Metabolic Syndrome
      Among US Adults With Osteoarthritis.
AB  - OBJECTIVE: To investigate the association between objectively measured physical
      activity and metabolic syndrome among adults with osteoarthritis (OA). METHODS:
      Using cross-sectional data from the 2003-2006 National Health and Nutrition
      Examination Survey, we identified 566 adults with OA with available accelerometer
      data assessed using Actigraph AM-7164 and measurements necessary to determine
      metabolic syndrome by the Adult Treatment Panel III. Analysis of variance was
      conducted to examine the association between continuous variables in each
      activity level and metabolic syndrome components. Logistic models estimated the
      relationship of quartile of daily minutes of different physical activity levels
      to odds of metabolic syndrome adjusted for socioeconomic and health factors.
      RESULTS: Among persons with OA, most were women average age of 62.1 years and
      average disease duration of 12.9 years. Half of adults with OA had metabolic
      syndrome (51.0%; 95% confidence interval [95% CI] 44.2%-57.8%), and only 9.6%
      engaged in the recommended 150 minutes per week of moderate/vigorous physical
      activity. Total sedentary time was associated with higher rates of metabolic
      syndrome and its components, while light and objectively measured
      moderate/vigorous physical activity was inversely associated with metabolic
      syndrome and its components. Higher levels of light activity were associated with
      lower prevalence of metabolic syndrome (quartile 4 versus quartile 1: adjusted
      odds ratio 0.45, 95% CI 0.24-0.84, P for linear trend < 0.005). CONCLUSION: Most
      US adults with OA are sedentary. Increased daily minutes in physical activity,
      especially in light intensity, is more likely to be associated with decreasing
      prevalence of metabolic syndrome among persons with OA.

PMID- 25777464
TI  - Water, air, Earth and cosmic radiation.
AB  - In the context of the origin of life, rocks are considered mainly for catalysis
      and adsorption-desorption processes. Here it is shown how some rocks evolve in
      energy and might induce synthesis of molecules of biological interest.
      Radioactive rocks are a source of thermal energy and water radiolysis producing
      molecular hydrogen, H2. Mafic and ultramafic rocks evolve in water and dissolved
      carbon dioxide releasing thermal energy and H2. Peridotites and basalts contain
      ferromagnesian minerals which transform through exothermic reactions with the
      generation of heat. These reactions might be triggered by any heating process
      such as radioactive decay, hydrothermal and subduction zones or post-shock of
      meteorite impacts. H2 might then be generated from endothermic hydrolyses of the
      ferromagnesian minerals olivine and pyroxene. In both cases of mafic and
      radioactive rocks, production of CO might occur through high temperature
      hydrogenation of CO2. CO, instead of CO2, was proven to be necessary in
      experiments synthesizing biological-type macromolecules with a gaseous mixture of
      CO, N2 and H2O. In the geological context, N2 is present in the environment, and
      the activation source might arise from cosmic radiation and/or radionuclides.
      Ferromagnesian and radioactive rocks might consequently be a starting point of an
      hydrothermal chemical evolution towards the abiotic formation of biological
      molecules. The two usually separate worlds of rocks and life are shown to be
      connected through molecular and thermodynamic chemical evolution. This concept
      has been proposed earlier by the author (Bassez J Phys: Condens Matter 15:L353
      L361, 2003, 2008a, 2008b; Bassez Orig Life Evol Biosph 39(3-4):223-225, 2009;
      Bassez et al. 2011; Bassez et al. Orig Life Evol Biosph 42(4):307-316, 2012,
      Bassez 2013) without thermodynamic details. This concept leads to signatures of
      prebiotic chemistry such as radionuclides and also iron and magnesium carbonates
      associated with serpentine and/or talc, which were discussed at the 2014 European
      Astrobiology Network Association conference on Signatures of Life. 

PMID- 25777465
TI  - M2 proton channel: toward a model of a primitive proton pump.
AB  - Transmembrane proton transfer was essential to early cellular systems in order to
      transduce energy for metabolic functions. The reliable, efficient and controlled
      generation of proton gradients became possible only with the emergence of active
      proton pumps. On the basis of features shared by most modern proton pumps we
      identify the essential mechanistic steps in active proton transport. Further, we
      discuss the mechanism of action of a small, transmembrane M2 proton channel from
      influenza A virus as a model for proton transport in protocells. The M2 channel
      is a 94-residue long, alpha-helical tetramer that is activated at low pH and
      exhibits high selectivity and directionality. A shorter construct, built of
      transmembrane fragments that are only 24 amino acids in length, exhibits very
      similar proton transport properties. Molecular dynamics simulations on the
      microsecond time-scale carried out for the M2 channel provided atomic level
      details on the activation of the channel in response to protonation of the
      histidine residue, His37. The pathway of proton conduction is mediated by His37,
      which accepts and donates protons at different interconverting conformation
      states when pH is lower than 6.5. The Val27 and Trp41 gates and the salt bridge
      between Asp44 and Arg45 further enhance the directionality of proton transport.
      It is argued that the architecture and the mechanism of action similar to that
      found in the M2 channel might have been the perfect starting point for evolution
      towards the earliest proton pumps, indicating that active proton transport could
      have readily emerged from simple, passive proton channels. 

PMID- 25777466
TI  - Reply to: No correlation between estimated and actual glomerular filtration rates
      in pediatric oncology patients.

PMID- 25777467
TI  - Phase I study of the anti-MET antibody onartuzumab in patients with solid tumors
      and MET-positive lung cancer.
AB  - Onartuzumab is a monovalent, humanized, monoclonal antibody that showed
      significant survival benefits in combination with erlotinib in MET-positive non
      small-cell lung cancer (NSCLC) in pre-specified subgroup analyses of a randomized
      phase II study. We conducted a two-stage, open-label, multicenter, phase I study
      of onartuzumab in Japanese patients. Stage 1 investigated the safety,
      tolerability, pharmacokinetics (PK), and recommended dose of onartuzumab in
      patients with solid tumors, and Stage 2 determined the safety, tolerability, and
      PK of onartuzumab plus erlotinib in patients with MET-positive NSCLC. Nine
      patients received onartuzumab monotherapy (4, 15, or 30 mg/kg on Day 1 of each 21
      day cycle) in Stage 1, and six patients received onartuzumab (15 mg/kg) plus
      erlotinib (150 mg/day) in Stage 2. There were no dose-limiting toxicities in
      either stage. Serious adverse events (AEs) occurred in one patient in Stage 1
      (convulsion), and two patients in Stage 2 (once case each of diarrhea, vomiting,
      and pulmonary embolism), but there were no grade 4 AEs or AEs leading to death.
      Onartuzumab PKs were linear in the dose range of 4 to 30 mg/kg, and were not
      affected by co-administration with erlotinib. PK parameters of onartuzumab were
      similar to those reported in non-Japanese patients. A partial response was
      observed in a patient with MET immunohistochemistry 3+ NSCLC without MET gene
      amplification. Based on these results, the recommended dose of onartuzumab in
      Japanese patients with solid tumors is 15 mg/kg every 21 days. The combination of
      onartuzumab with erlotinib is feasible in Japanese patients with MET-positive
      lung cancer.

PMID- 25777469
TI  - Primary and secondary literature should be distinguished when searching for data
      used in systematic reviews of nosocomial outbreaks.

PMID- 25777468
TI  - Phase 1 study of ixazomib, an investigational proteasome inhibitor, in advanced
      non-hematologic malignancies.
AB  - PURPOSE: Ixazomib is an investigational proteasome inhibitor with demonstrated
      antitumor activity in xenograft models of multiple myeloma (MM), lymphoma, and
      solid tumors. This open-label, phase 1 study investigated intravenous (IV)
      ixazomib, in adult patients with advanced non-hematologic malignancies. METHODS:
      Patients received IV ixazomib twice-weekly for up to twelve 21-day cycles. The
      0.125 mg/m(2) starting dose was doubled (one patient/dose) until 1.0 mg/m(2)
      based on dose-limiting toxicities (DLTs) in cycle 1. This was followed by 3 + 3
      dose-escalation and expansion at the maximum tolerated dose (MTD). Primary
      objectives included safety and MTD assessment. Secondary objectives included
      assessment of pharmacokinetics, pharmacodynamics, and disease response. RESULTS:
      Ixazomib was escalated from 0.125 to 2.34 mg/m(2) to determine the MTD (n = 23);
      patients were then enrolled to MTD expansion (n = 73) and pharmacodynamic (n =
      20) cohorts. Five patients experienced DLTs (1.0 and 1.76 mg/m(2): grade 3
      pruritic rash; 2.34 mg/m(2): grade 3 and 4 thrombocytopenia, and grade 3 acute
      renal failure); thus, the MTD was 1.76 mg/m(2). Drug-related grade >=3 adverse
      events (AEs) included thrombocytopenia (23 %), skin and subcutaneous (SC) tissue
      disorders (16 %), and fatigue (9 %). Among 92 evaluable patients, one (head and
      neck cancer) had a partial response and 30 had stable disease. Ixazomib terminal
      half-life was 3.8-7.2 days; plasma exposures increased dose-proportionally and
      drug was distributed to tumors. Inhibition of whole-blood 20S proteasome activity
      and upregulation of ATF-3 in tumor biopsies demonstrated target engagement.
      CONCLUSIONS: In patients with solid tumors, ixazomib was associated with a
      manageable safety profile, limited antitumor activity, and evidence of downstream
      proteasome inhibition effects.

PMID- 25777470
TI  - Trypsin from unicorn leatherjacket (Aluterus monoceros) pyloric caeca:
      purification and its use for preparation of fish protein hydrolysate with
      antioxidative activity.
AB  - BACKGROUND: Fish proteases, especially trypsin, could be used to prepare fish
      protein hydrolysates with antioxidative activities. In this study, trypsin from
      the pyloric caeca of unicorn leatherjacket was purified by ammonium sulfate
      precipitation and soybean trypsin inhibitor (SBTI)-Sepharose 4B affinity
      chromatography. Hydrolysate from Indian mackerel protein isolate with different
      degrees of hydrolysis (20, 30 and 40% DH) was prepared using the purified
      trypsin, and antioxidative activities (1,1-diphenyl-2-picrylhydrazyl and 2,2'
      azinobis(3-ethylbenzothiazoline-6-sulfonic acid) radical-scavenging activities,
      ferric-reducing antioxidant power and ferrous-chelating activity) of the
      hydrolysate were determined. RESULTS: Trypsin was purified 26.43-fold with a
      yield of 13.43%. The purified trypsin had a molecular weight (MW) of 23.5 kDa and
      optimal activity at pH 8.0 and 55  degrees C. It displayed high stability in the
      pH range of 6.0-11.0 and was thermally stable up to 50  degrees C. Both SBTI
      (0.05 mmol L(-1)) and N-p-tosyl-L-lysine-chloromethylketone (5 mmol L(-1))
      completely inhibited trypsin activity. Antioxidative activities of the
      hydrolysate from Indian mackerel protein isolate increased with increasing DH up
      to 40% (P < 0.05). Based on sodium dodecyl sulfate polyacrylamide gel
      electrophoresis, the hydrolysate with 40% DH had a MW lower than 6.5 kDa.
      CONCLUSION: The purified protease from unicorn leatherjacket pyloric caeca was
      identified as trypsin based on its ability to hydrolyze a specific synthetic
      substrate and the response to specific trypsin inhibitors. The purified trypsin
      could hydrolyze Indian mackerel protein isolate, and the resulting hydrolysate
      exhibited antioxidative activity depending on its DH.

PMID- 25777471
TI  - Bioactive proteins from Solanaceae as quorum sensing inhibitors against virulence
      in Pseudomonas aeruginosa.
AB  - Cell-to-cell communication or quorum sensing (QS) is a generic event in bacteria
      that is used to coordinate gene expression among local populations. The
      phenomenon of QS depends on the fact that presence of sufficient bacteria
      ascertains a threshold level of autoinducer concentration that allows bacteria to
      sense a critical cell mass and to activate or repress target genes. Thus, QS has
      been an attractive target for the development of anti-infective strategies that
      are not based on the use of antibiotics. Several anti-QS approaches have been
      demonstrated including natural products from plant-based secondary metabolites.
      However, the role of plant bioactive proteins as an anti-QS peptide is yet to be
      deciphered. Against a backdrop of ever-increasing antibiotic resistant pathogens,
      there is a strong need for development of alternative therapeutic strategies.
      Thus, our hypothesis is that bioactive proteins from the plant family Solanaceae
      are quorum quenching molecules that can be exploited to develop a therapeutic
      strategy against virulence. We presume that bioactive proteins will inactivate or
      inhibit or degrade QS signals from bacteria to prevent cell-to-cell communication
      and thus inhibit development of virulence in Pseudomonas aeruginosa. Further, the
      use of proteins as quorum quenchers will delay the bacteria to develop resistance
      against these quenching molecules. 

PMID- 25777472
TI  - In this correspondence, preliminary data in 100 lithium users found that urine
      osmolality correlated with chronic kidney disease, diabetes mellitus, and
      hypothyroidism. We hypothesize that GSK-3beta inhibition is a potential mechanism
      for lithium-associated medical illness.

PMID- 25777473
TI  - Working conditions and psychotropic drug use: cross-sectional and prospective
      results from the French national SIP study.
AB  - Prospective studies exploring the associations between a large range of
      occupational factors and psychotropic drug use among national samples of workers
      are seldom. This study investigates the cross-sectional and prospective
      associations between occupational factors, including a large set of psychosocial
      work factors, and psychotropic drug use in the national French working
      population. The study sample comprised 7542 workers for the cross-sectional
      analysis and 4213 workers followed up for a 4-year period for the prospective
      analysis. Psychotropic drug use was measured within the last 12 months and
      defined by the use of antidepressants, anxiolytics or hypnotics. Three groups of
      occupational factors were explored: classical and emergent psychosocial work
      factors, working time/hours and physical work exposures. Weighted Poisson
      regression analyses were performed to adjust for covariates. In the cross
      sectional analysis, psychological demands, low social support and hiding emotions
      were associated with psychotropic drug use. Job insecurity for men and night work
      for women were associated with psychotropic drug use. In the prospective
      analysis, hiding emotions and physical exposure were predictive of psychotropic
      drug use. Dose-response associations were observed for the frequency/intensity of
      exposure and repeated exposure to occupational factors. This study underlines the
      role of psychosocial work factors, including emergent factors, in psychotropic
      drug use. Prevention policies oriented toward psychosocial work factors
      comprehensively may be useful to reduce this use. 

PMID- 25777474
TI  - Lexical analysis in schizophrenia: how emotion and social word use informs our
      understanding of clinical presentation.
AB  - BACKGROUND: The words people use convey important information about internal
      states, feelings, and views of the world around them. Lexical analysis is a fast,
      reliable method of assessing word use that has shown promise for linking speech
      content, particularly in emotion and social categories, with psychopathological
      symptoms. However, few studies have utilized lexical analysis instruments to
      assess speech in schizophrenia. In this exploratory study, we investigated
      whether positive emotion, negative emotion, and social word use was associated
      with schizophrenia symptoms, metacognition, and general functioning in a
      schizophrenia cohort. METHODS: Forty-six participants generated speech during a
      semi-structured interview, and word use categories were assessed using a
      validated lexical analysis measure. Trained research staff completed symptom,
      metacognition, and functioning ratings using semi-structured interviews. RESULTS:
      Word use categories significantly predicted all variables of interest, accounting
      for 28% of the variance in symptoms and 16% of the variance in metacognition and
      general functioning. Anger words, a subcategory of negative emotion,
      significantly predicted greater symptoms and lower functioning. Social words
      significantly predicted greater metacognition. CONCLUSIONS: These findings
      indicate that lexical analysis instruments have the potential to play a vital
      role in psychosocial assessments of schizophrenia. Future research should
      replicate these findings and examine the relationship between word use and
      additional clinical variables across the schizophrenia-spectrum.

PMID- 25777475
TI  - In Vitro and In Vivo Evaluation of Small Cationic Abiotic Lipopeptides as Novel
      Antifungal Agents.
AB  - We investigated the antifungal potential of short lipopeptides against clinical
      fungal isolates with an objective to evaluate their clinical feasibility. All
      tested lipopeptides exhibit good antifungal activity with negligible difference
      between the MICs against susceptible and drug-resistant clinical fungal isolates.
      The MTT assay results revealed the lower cytotoxicity of lipopeptides toward
      mammalian cells (NRK-52E). In particular, LP24 displayed highest potency against
      most of the tested fungal isolates with MICs in the range of 1.5-4.5 MUg/mL.
      Calcein dye leakage experiments with model membrane suggested the membrane-active
      mode of action for LP24. Extending our work from model membranes to intact
      Aspergillus fumigatus in scanning electron micrographs, we could visualize
      surface perturbation caused by LP24. LP24 (5 mg/kg) significantly reduces the A.
      fumigatus burden among the various organs of infected animals, and 70% of the
      infected mice survived when observed for 28 days. This study underscores the
      potential of small cationic abiotic lipopeptides to develop into the next
      generation antimicrobial therapy. 

PMID- 25777477
TI  - Simultaneous determination of seven gestagens in kidney fats by Ultra Performance
      Convergence Chromatography tandem mass spectrometry.
AB  - An ultra-performance convergence chromatography (UPC2) system coupled tandem mass
      spectrometry was successfully utilised to analyse chlormadinone acetate,
      delmadinone acetate, fluorogestone acetate, medroxyprogesterone acetate,
      megestrol acetate, melengestrol acetate, chlortestasterone acetate in bovine and
      porcine kidney fat. This novel approach obtained an improved resolution in
      comparison to previously reported chromatographic methods combined with MS
      detector in a shorter analytical time. All the acetylgestagen compounds were well
      separated on a ACQUITY UPC(2) HSS C18 column (3.0 * 100 mm, 1.7 MUm) by applying
      methanol and carbon dioxide (2/98). The LOQ of delmadinone acetate, melengestrol
      acetate, medroxyprogesterone acetate and megestrol acetate are 0.5 MUg/kg,
      fluorogestone acetate, chlormadinone acetate and chlortestasterone acetate 1.0
      MUg/kg. The recoveries of gestagens spiked in kidney fats at a concentration
      range of 0.5 to 4 MUg/kg were above 86.1% with relative standard deviations (RSD)
      less than 13.1%. These rapid and reliable methods can be used to efficiently
      separate, characterize and quantify the residues of gestagens in kidney fats with
      advantages of shorter time, more sensitive and environmental friendly.

PMID- 25777478
TI  - Comprehensive analysis of the lipophilic reactive carbonyls present in biological
      specimens by LC/ESI-MS/MS.
AB  - A new analytical method has been developed for profiling lipophilic reactive
      carbonyls (RCs) such as aldehydes and ketones in biological samples using liquid
      chromatography/electrospray ionization tandem mass spectrometry (LC/ESI-MS/MS)
      with selected reaction monitoring (SRM). The method consists of several phases,
      including (1) extraction of lipophilic RCs with a chloroform/methanol mixture;
      (2) derivatization of the extracted RCs with dansyl hydrazine (DH); and (3) SRM
      detection of the characteristic product ion of the 5-dimethylaminonaphthalene-1
      sulfonyl moiety (m/z 236.1). The analytical results were expressed as RC maps,
      which allowed for the occurrence and levels of different lipophilic RCs to be
      visualized. We also developed a highly reproducible and accurate method to
      extract, purify and derivatize RCs in small volumes of biological specimens. This
      method was applied to the detection of free RCs in mice plasma samples, and
      resulted in the detection of more than 400 RCs in samples obtained from C57BL/6J
      mice. Thirty-four of these RCs were identified by comparison with authentic RCs.
      This method could be used to investigate the levels of RCs in biological and
      environmental samples, as well as studying the role of lipid peroxidation in
      oxidative stress related-disorders and discovering new biomarkers for the early
      diagnosis of these diseases. 

PMID- 25777479
TI  - LC-MS/MS analysis of pramipexole in mouse plasma and tissues: elimination of
      lipid matrix effects using weak cation exchange mode based solid-phase
      extraction.
AB  - Intranasal delivery is emerging as a promising alternative for oral or
      intravenous administration of central nervous system (CNS) drugs, such as
      pramipexole which is widely used for the treatment of Parkinson's disease. To
      evaluate the effectiveness of intranasal delivery of pramipexole, preclinical
      pharmacokinetic and tissue distribution studies following intranasal
      administration need to be investigated. In this paper, we developed and validated
      a robust and sensitive LC-MS/MS assay without matrix effect for accurate
      measurements of pramipexole in mouse plasma and tissue samples. Pramipexole and
      its stable isotope labeled internal standard (d3-pramipexole) were extracted from
      biological samples by protein precipitation (PPT) coupled with solid phase
      extraction (SPE) using weak cation exchange SPE cartridges. Matrix effects were
      studied using post-column infusion and post-extraction addition experiments by
      direct monitoring of typical phospholipids including glycerophosphocholines
      (GPChos) and lysoglycerophosphocholines (Lyso-GPChos). Chromatographic separation
      was achieved on a Welch Ultimate((r)) XB-CN column using isocratic elution with a
      run time of 3.0 min. The assay was linear in the concentration range of 0.05-100
      ng/mL and the intra- and inter-day precision and accuracy met the acceptance
      criteria. Compared with previous reported assays, the current sample preparation
      approach exhibited significant reduction of matrix effects due to the
      dramatically decreased levels of residual matrix components such as GPChos and
      Lyso-GPChos. This method has been successfully applied to pharmacokinetic and
      tissue distribution studies of pramipexole in mice following a single intravenous
      or intranasal dose of 50 MUg/kg.

PMID- 25777480
TI  - Development of a tandem affinity phosphoproteomic method with motif selectivity
      and its application in analysis of signal transduction networks.
AB  - Phosphorylation is an important post-translational modification that is involved
      in regulating many signaling pathways. Of particular interest are the growth
      factor mediated Ras and phosphoinositide 3-kinase (PI3K) signaling pathways
      which, if misregulated, can contribute to the progression of cancer.
      Phosphoproteomic methods have been developed to study regulation of signaling
      pathways; however, due to the low stoichiometry of phosphorylation, understanding
      these pathways is still a challenge. In this study, we have developed a multi
      dimensional method incorporating electrostatic repulsion-hydrophilic interaction
      chromatography (ERLIC) with tandem IMAC/TiO2 enrichment for subsequent
      phosphopeptide identification by LC/MS/MS. We applied this method to PDGF
      stimulated NIH 3T3 cells to provide over 11,000 unique phosphopeptide
      identifications. Upon motif analysis, IMAC was found to enrich for basophilic
      kinase substrates while the subsequent TiO2 step enriched for acidophilic kinase
      substrates, suggesting that both enrichment methods are necessary to capture the
      full complement of kinase substrates. Biological functions that were over
      represented at each PDGF stimulation time point, together with the
      phosphorylation dynamics of several phosphopeptides containing known kinase
      phosphorylation sites, illustrate the feasibility of this approach in
      quantitative phosphoproteomic studies. 

PMID- 25777481
TI  - Repeated low-dose 17beta-estradiol treatment prevents activation of apoptotic
      signaling both in the synaptosomal and cellular fraction in rat prefrontal cortex
      following cerebral ischemia.
AB  - Disturbance in blood circulation is associated with numerous pathological
      conditions characterized by cognitive decline and neurodegeneration. Activation
      of pro-apoptotic signaling previously detected in the synaptosomal fraction may
      underlie neurodegeneration in the prefrontal cortex of rats submitted to
      permanent bilateral common carotid arteries occlusion (two-vessel occlusion,
      2VO). 17beta-Estradiol (E) exerts potent neuroprotective effects in the brain
      affecting, among other, ischemia-induced pathological changes. As most
      significant changes in rats submitted to 2VO were observed on 7th day following
      the insult, of interest was to examine whether 7 day treatment with low dose of E
      (33.3 ug/kg/day) prevents formerly reported neurodegeneration and may represent
      additional therapy during the early post-ischemic period. Role of E treatment on
      apoptotic pathway was monitored on Bcl-2 family members, cytochrome c, caspase 3
      and PARP protein level in the synaptosomal (P2) fraction of the prefrontal
      cortex. Furthermore, changes of these proteins were examined in the cytosolic,
      mitochondrial and nuclear fraction, with the emphasis on potential involvement of
      extracellular signal-regulated kinases (ERK) and protein kinase B (Akt)
      activation and their role in nuclear translocation of transcriptional nuclear
      factor kappa B (NF-kB) associated with alteration of Bax and Bcl-2 gene
      expression. The extent of cellular damage was determined using DNA fragmentation
      and Fluoro-Jade B staining. The absence of activation of apoptotic cascade both
      in the P2 and cell accompanied with decreased DNA fragmentation and number of
      degenerating neurons clearly indicates that E treatment ensures the efficient
      protection against ischemic insult. Moreover, E-mediated modulation of pro
      apoptotic signaling in the cortical cellular fractions involves cooperative
      activation of ERK and Akt, which may be implicated in the observed prevention of
      neurodegenerative changes.

PMID- 25777482
TI  - Evaluation of a Streptococcus thermophilus strain with innate anti-inflammatory
      properties as a vehicle for IL-10 cDNA delivery in an acute colitis model.
AB  - The aim of this work was to develop a Streptococcus (S.) thermophilus strain with
      improved anti-inflammatory properties due to the incorporation of the therapeutic
      cDNA delivery plasmid pValac::il-10. To achieve this purpose, cells of S.
      thermophilus CRL807, previously selected as being an important anti-inflammatory
      strain, were electroporated with pValac::il-10 plasmid. In order to confirm the
      functionality of the developed strain, it was co-cultured with human epithelial
      cells Caco-2 and the production of IL-10 was evaluated by ELISA. Bacterial
      suspensions of S. thermophilus CRL807 containing pValac::il-10 plasmid or of the
      wild-type (WT) strain were administered in vivo using a murine model of
      intestinal inflammation. The animals treated with S. thermophilus CRL807
      pValac::il-10 showed a lower body weight loss, microbial translocation to liver
      and damage scores in their intestines at macroscopical and microscopic levels.
      Furthermore, a significant increase was observed in the concentration of IL-10 in
      the intestinal contents of these mice compared to the rest of the experimental
      groups, accompanied by decreased levels of pro-inflammatory cytokines. The
      insertion of the therapeutic pValac::il-10 plasmid increased the intrinsic anti
      inflammatory activity (synergetic effect) of S. thermophilus CRL807 which could
      be included in novel treatment protocols for inflammatory bowel diseases. 

PMID- 25777483
TI  - Astaxanthin and withaferin A block paracrine cytokine interactions between UVB
      exposed human keratinocytes and human melanocytes via the attenuation of
      endothelin-1 secretion and its downstream intracellular signaling.
AB  - BACKGROUND: Paracrine interactions between keratinocytes and melanocytes via
      cytokines play an essential role in regulating pigmentation in epidermal
      hyperpigmentary disorders. There is an urgent need for a human epidermal model in
      which melanogenic paracrine interactions between UVB-exposed keratinocytes and
      melanocytes can be precisely evaluated because human epidermal equivalents
      consisting of multilayered keratinocytes and melanocytes have significant
      limitations in this respect. OBJECTIVE: To resolve this challenge, we established
      a co-culture system with cell inserts using human keratinocytes and human
      melanocytes that serves as an appropriate new model for UVB-induced
      hyperpigmentation. Using that new model, we examined the blocking effects of two
      natural chemicals, astaxanthin and withaferin A, on paracrine cytokine
      interactions between UVB-exposed keratinocytes and melanocytes and characterized
      their mechanisms of action. METHODS AND RESULTS: RT-PCR analysis showed that co
      culture of human keratinocytes that had been exposed to UVB significantly
      stimulated human melanocytes to increase their expression of genes encoding
      microphthalmia-associated transcription factor, tyrosinase and tyrosinase-related
      protein 1. The catalytic activity of tyrosinase was also increased. ELISA assays
      revealed that UVB significantly increased the secretion of interleukin-1alpha,
      interleukin-6/8, granulocyte macrophage stimulatory factor and endothelin-1 but
      not alpha-melanocyte stimulating hormone. The addition of an endothelin-1
      neutralizing antibody significantly abrogated the increase of tyrosinase
      activity. Post-irradiation treatment with astaxanthin or withaferin A
      significantly abolished the up-regulation of tyrosinase activity induced by UVB.
      Treatment with astaxanthin or withaferin A significantly reduced the increased
      levels of interleukin-1alpha, interleukin-6/8, granulocyte macrophage stimulatory
      factor and endothelin-1. Withaferin A but not astaxanthin also significantly
      abrogated the endothelin-1-stimulated activity of tyrosinase in melanocytes.
      Western blot analysis of intracellular signaling factors revealed that withaferin
      A but not astaxanthin significantly abolished the endothelin-1-stimulated
      phosphorylation of Raf-1, MEK, ERK, MITF and CREB in human melanocytes.
      CONCLUSIONS: These results demonstrate that this co-culture system is an
      appropriate model to characterize melanogenic paracrine interactions and that
      astaxanthin and withaferin A serve as potent inhibitors of those interactions.
      Their effects are caused not only by down-regulating the increased secretion of
      an intrinsic melanogenic cytokine, endothelin-1, by UVB-exposed human
      keratinocytes, but also by interrupting the endothelin-1-triggered downstream
      intracellular signaling between protein kinase C and Raf-1 in human melanocytes
      (only for withaferin A).

PMID- 25777484
TI  - Association of socioeconomic status with sleep disturbances in the Swiss
      population-based CoLaus study.
AB  - OBJECTIVE: To examine the association of socioeconomic status (SES) with
      subjective and objective sleep disturbances and the role of socio-demographic,
      behavioural and psychological factors in explaining this association. METHODS:
      Analyses are based on 3391 participants (53% female, aged 40-81 years) of the
      follow-up of the CoLaus study (2009-2012), a population-based sample of the city
      of Lausanne, Switzerland. All participants completed a sleep questionnaire and a
      sub-sample (N = 1569) underwent polysomnography. RESULTS: Compared with men with
      a high SES, men with a low SES were more likely to suffer from poor sleep quality
      [prevalence ratio (PR) for occupational position = 1.68, 95% Confidence Interval
      (CI): 1.30-2.17], and to have long sleep latency (PR = 4.90, 95%CI: 2.14-11.17),
      insomnia (PR = 1.47, 95% CI: 1.12-1.93) and short sleep duration (PR = 3.03, 95%
      CI: 1.78-5.18). The same pattern was observed among women (PR = 1.29 for sleep
      quality, 2.34 for sleep latency, 2.01 for daytime sleepiness, 3.16 for sleep
      duration, 95%CIs ranging from 1.00 to 7.51). Use of sleep medications was not
      patterned by SES. SES differences in sleep disturbances were only marginally
      attenuated by adjustment for other socio-demographic, behavioural and
      psychological factors. Results from polysomnography confirmed poorer sleep
      patterns among participants with low SES (p <0.05 for sleep efficiency/stage
      shifts), but no SES differences were found for sleep duration. CONCLUSIONS: In
      this population-based sample, low SES was strongly associated with sleep
      disturbances, independently of socio-demographic, behavioural, and psychological
      factors. Further research should establish the extent to which social differences
      in sleep contribute to socioeconomic differences in health outcomes.

PMID- 25777486
TI  - Vascular graft infections and role of PET/CT in patients with persistent
      bacteraemia.
AB  - Prosthetic vascular graft infection although a rare complication of vascular
      reconstruction surgery; has been associated with significant morbidity and
      mortality. The author presents two patients with prosthetic aortic graft
      presenting as fever and methicillin sensitive Staphylococcus aureus bacteraemia
      without any other localising sign of infection. Both patients had a history of
      postoperative wound infection after their graft placement. Patients remained
      persistently bacteraemic on appropriate antimicrobial therapy making the
      clinician suspicious of a vascular graft infection. A [18 F] fluoro-2-deoxy-d
      glucose positron emission tomography associated to CT scan was used to identify
      the prosthetic vascular graft infection and since both patients were high-risk
      surgical candidates, a conservative medical approach was used. They were treated
      with 6 weeks of nafcillin and rifampin, followed by long-term doxycycline for
      suppression. This highlights the importance of considering vascular graft
      infection in patients with recurrent and persistent bacteraemia despite adequate
      therapy.

PMID- 25777485
TI  - Adverse childhood experiences are associated with adult sleep disorders: a
      systematic review.
AB  - Adverse childhood experiences (ACEs) represent substantial threats to public
      health and affect about 58% of youth in the US. In addition to their acute
      effects such as injury and physical trauma, ACEs are associated with an increased
      risk of several negative health outcomes throughout the life course. Emerging
      evidence suggests that sleep disorders may be one such outcome, but existing
      studies have not been systematically reviewed and summarized. We conducted a
      systematic review to summarize the evidence concerning the relationship between
      ACEs and sleep disorders and disturbances, with a focus on adult women. Original
      publications were identified through searches of the electronic databases
      MEDLINE, Embase, and Web of Science using the keywords "childhood," "adversity,"
      "abuse," and "sleep" as well as searches of the reference lists of eligible
      studies. Studies evaluating ACEs that occurred before 18 years of age and sleep
      outcomes that were assessed at 18 years or older were adjudicated and included. A
      total of 30 publications were identified. Of the 30 studies, 28 were
      retrospective analyses and there was vast heterogeneity in the types of ACEs and
      sleep outcomes measured. The majority of retrospective studies (N = 25 of 28)
      documented statistically significant associations between sleep disorders
      including sleep apnea, narcolepsy, nightmare distress, sleep paralysis, and
      psychiatric sleep disorders with a history of childhood adversity. In many
      studies, the strengths of associations increased with the number and severity of
      adverse experiences. These associations were corroborated by the two prospective
      studies published to date. Notably, investigators have documented statistically
      significant associations between family conflict at 7-15 years of age and
      insomnia at 18 years of age (odds ratio, OR = 1.4; 95% confidence interval, CI =
      1.2-1.7) and between childhood sexual abuse and sleep disturbances 10 years later
      in adult women (beta = 0.24, p <0.05). There is a growing scientific body of
      knowledge suggesting an association between ACEs and multiple sleep disorders in
      adulthood. The available evidence indicates the need to develop treatment
      strategies such as trauma-informed care for survivors of abuse who suffer from
      sleep disorders and disturbances. Further, longitudinal studies among diverse
      populations are needed to improve the overall understanding of this association
      and to investigate potential gender and racial/ethnic disparities in the strength
      of the association. 

PMID- 25777487
TI  - Apparent asystole: are we missing a lifesaving opportunity?
AB  - The use of ultrasonography is rapidly expanding in emergency medicine. Real-time
      assessment offers clues to prompt diagnosis and creates opportunities for speedy
      intervention. We present a case of 'cardiac monitor asystole' that proved to be
      ventricular fibrillation on ultrasound examination. Uniquely this case
      demonstrates that this, typically unrecognised, form of ventricular fibrillation
      responds to desynchronised defibrillation, with restoration of perfusion for
      approximately 30 min. With increasing access to ultrasound we believe that
      further research is indicated to determine whether some cases of apparent
      asystole may best be treated by defibrillation, presenting an opportunity to save
      more lives than current protocols achieve.

PMID- 25777488
TI  - The appropriate management of an appendiceal mucocele.
AB  - Appendicectomy is one of the most commonly performed surgical procedures.
      Appendiceal mucocele is a relative rare disease, but appropriate management is
      critical. Indeed, the intact removal of a mucocele represents a curative
      treatment; conversely, a rupture may result in the spread of epithelial cells
      throughout the peritoneal cavity (pseudomyxoma peritonei). We report a case of a
      61-year-old woman, admitted to our department, who underwent resection of an
      appendiceal mucocele, focusing, in the discussion, on the clinical and surgical
      management of this disease. 

PMID- 25777489
TI  - Atypical cardiac tamponade in severe pulmonary hypertension.

PMID- 25777490
TI  - Primary malignant mixed Mullerian tumour of the fallopian tube: a rare and
      difficult but possible diagnosis.

PMID- 25777491
TI  - Milder course in Duchenne patients with nonsense mutations and no muscle
      dystrophin.

PMID- 25777492
TI  - Response to: Milder course in Duchenne patients with nonsense mutations and no
      muscle dystrophin.

PMID- 25777493
TI  - A Virtual Childhood Obesity Collaborative: Satisfaction With Online Continuing
      Education.
AB  - INTRODUCTION: This descriptive study evaluated school-based health center (SBHC)
      providers' satisfaction with Web-based continuing education as part of a virtual
      childhood obesity intervention. METHOD: Thirty-six participants from 24 SBHCs in
      six states participated in the training modules. Modules were divided into four
      learning sessions, with a total of 17 training modules. Participants completed
      satisfaction surveys after each module, as well as an overall survey at the end
      of the training. Questions were rated on a 4-point Likert scale (4 = strongly
      agree, 3 = agree, 2 = disagree, 1 = strongly disagree). RESULTS: Participation in
      the first two learning sessions was higher than the last two. Provider
      satisfaction of training modules by question type and content area was quite high
      (MU = 3.66-3.33). Overall satisfaction means ranged from 3.76 to 3.24. Many
      providers also reported plans to make changes in their practice after completing
      the training. DISCUSSION: This study demonstrated that a virtual childhood
      obesity collaborative is an acceptable delivery method for continuing education.

PMID- 25777494
TI  - Strategies for the one-step immobilization-purification of enzymes as industrial
      biocatalysts.
AB  - In this review, we detail the efforts performed to couple the purification and
      the immobilization of industrial enzymes in a single step. The use of antibodies,
      the development of specific domains with affinity for some specific supports will
      be revised. Moreover, we will discuss the use of domains that increase the
      affinity for standard matrices (ionic exchangers, silicates). We will show how
      the control of the immobilization conditions may convert some unspecific supports
      in largely specific ones. The development of tailor-made heterofunctional
      supports as a tool to immobilize-stabilize-purify some proteins will be discussed
      in deep, using low concentration of adsorbent groups and a dense layer of groups
      able to give an intense multipoint covalent attachment. The final coupling of
      mutagenesis and tailor made supports will be the last part of the review. 

PMID- 25777495
TI  - Continuous cultivation of photosynthetic microorganisms: Approaches, applications
      and future trends.
AB  - The possibility of using photosynthetic microorganisms, such as cyanobacteria and
      microalgae, for converting light and carbon dioxide into valuable biochemical
      products has raised the need for new cost-efficient processes ensuring a constant
      product quality. Food, feed, biofuels, cosmetics and pharmaceutics are among the
      sectors that can profit from the application of photosynthetic microorganisms.
      Biomass growth in a photobioreactor is a complex process influenced by multiple
      parameters, such as photosynthetic light capture and attenuation, nutrient
      uptake, photobioreactor hydrodynamics and gas-liquid mass transfer. In order to
      optimize productivity while keeping a standard product quality, a permanent
      control of the main cultivation parameters is necessary, where the continuous
      cultivation has shown to be the best option. However it is of utmost importance
      to recognize the singularity of continuous cultivation of cyanobacteria and
      microalgae due to their dependence on light availability and intensity. In this
      sense, this review provides comprehensive information on recent breakthroughs and
      possible future trends regarding technological and process improvements in
      continuous cultivation systems of microalgae and cyanobacteria, that will
      directly affect cost-effectiveness and product quality standardization. An
      overview of the various applications, techniques and equipment (with special
      emphasis on photobioreactors) in continuous cultivation of microalgae and
      cyanobacteria are presented. Additionally, mathematical modeling, feasibility,
      economics as well as the applicability of continuous cultivation into large-scale
      operation, are discussed. 

PMID- 25777496
TI  - Speech repetition as a window on the neurobiology of auditory-motor integration
      for speech: A voxel-based lesion symptom mapping study.
AB  - For more than a century, speech repetition has been used as an assay for gauging
      the integrity of the auditory-motor pathway in aphasia, thought classically to
      involve a linkage between Wernicke's area and Broca's area via the arcuate
      fasciculus. During the last decade, evidence primarily from functional imaging in
      healthy individuals has refined this picture both computationally and
      anatomically, suggesting the existence of a cortical hub located at the parietal
      temporal boundary (area Spt) that functions to integrate auditory and motor
      speech networks for both repetition and spontaneous speech production. While
      functional imaging research can pinpoint the regions activated in
      repetition/auditory-motor integration, lesion-based studies are needed to infer
      causal involvement. Previous lesion studies of repetition have yielded mixed
      results with respect to Spt's critical involvement in speech repetition. The
      present study used voxel-based lesion symptom mapping (VLSM) to investigate the
      neuroanatomy of repetition of both real words and non-words in a sample of 47
      patients with focal left hemisphere brain damage. VLSMs identified a large voxel
      cluster spanning gray and white matter in the left temporal-parietal junction,
      including area Spt, where damage was significantly related to poor non-word
      repetition. Repetition of real words implicated a very similar dorsal network
      including area Spt. Cortical regions including Spt were implicated in repetition
      performance even when white matter damage was factored out. In addition, removing
      variance associated with speech perception abilities did not alter the overall
      lesion pattern for either task. Together with past functional imaging work, our
      results suggest that area Spt is integral in both word and non-word repetition,
      that its contribution is above and beyond that made by white matter pathways, and
      is not driven by perceptual processes alone. These findings are highly consistent
      with the claim that Spt is an area of sensory-motor translation in speech
      processing. 

PMID- 25777497
TI  - Effect of vitamin E on lead exposure-induced learning and memory impairment in
      rats.
AB  - Chronic lead (Pb(2+)) exposure has been associated with learning and memory
      impairments, whereas vitamin E improves cognitive deficits. In this study, using
      a passive avoidance learning model in rats, we investigated the effects of
      vitamin E on Pb(2+) exposure-induced learning and memory impairments in rats. In
      the present study, 56 Wistar male rats (weighting 230-250g) were divided into
      eight groups (n=7). The Pb(2+) exposure involved gavages of lead acetate solution
      using three different doses (0.05%, 0.1%, and 0.2%) and the vitamin E consisted
      of three different doses (10, 25, 50MUg/rat) for 30days. After the 30-day period,
      the rats were tested using a passive avoidance task (acquisition test). In a
      retrieval test conducted 48h after the training, step through latency (STL) and
      time in the dark compartment (TDC) were recorded. The statistical analysis of
      data was performed using ANOVA followed by Tukey's post hoc analysis. In all
      cases, differences were considered significant if p<0.05. The results of the
      present study showed that chronic exposure to high doses of Pb(2+) significantly
      increased both the number of trails required for learning and the TDC, whereas it
      decreased the STL in the passive avoidance test. Administration of vitamin E
      ameliorated the effects of Pb(2+) on animal behavior in the passive avoidance
      learning and memory task. Our results indicate that impairments of learning and
      memory in Pb(2+)-exposed rats are dose dependent and can be inhibited by
      antioxidants such as vitamin E. 

PMID- 25777498
TI  - Prenatal maternal stress predicts reductions in CD4+ lymphocytes, increases in
      innate-derived cytokines, and a Th2 shift in adolescents: Project Ice Storm.
AB  - The relationship between psychological stress and immunity is well established,
      but it is not clear if prenatal maternal stress (PNMS) affects the development of
      the immune system in humans. Our objective was to determine the extent of this
      influence in a sample of teenagers whose mothers were pregnant during the 1998
      Quebec ice storm. As part of a longitudinal study of PNMS, we measured the
      objective stress exposure and subjective distress of the women soon after the
      disaster. We obtained blood samples from 37 of their children when they were
      13years old to measure cell population percentages and mitogen-induced cytokine
      production. We found that the mothers' objective degree of PNMS exposure
      significantly predicted reductions in total and CD4+ lymphocyte proportions,
      increases in TNF-alpha, IL-1beta, and IL-6 levels, and an enhancement of the Th2
      cytokines IL-4 and IL-13. Sex and timing of PNMS exposure during gestation were
      also associated with some outcomes. These results show that PNMS is a programming
      factor that can produce long-lasting consequences on immunity, potentially
      explaining non-genetic variability in immune-related disorders. This information
      contributes to the understanding of the mechanisms underlying the influence of
      PNMS on immune-mediated disorders in humans. 

PMID- 25777499
TI  - Conversations that matter.

PMID- 25777500
TI  - Effects of sodium tri- and hexametaphosphate on proliferation, differentiation,
      and angiogenic potential of human dental pulp cells.
AB  - INTRODUCTION: This study aimed to investigate the effects of 2 inorganic
      polyphosphates (poly[P]) are linear polymers of orthophosphate (Pi) residues
      linked by energy-rich phosphoanhydride poly(P) compounds, sodium triphosphate
      (STP, Na5P3O10) and sodium hexametaphosphate (SHMP, Na15P13O40 ~ Na20P18O40) on
      the proliferation, odontoblastic differentiation, and angiogenic potential of
      human dental pulp cells (HDPCs). METHODS: Differentiation was measured by
      alkaline phosphatase activity, calcified nodule formation by alizarin red
      staining, and marker messenger RNA (mRNA) levels by reverse-transcription
      polymerase chain reaction. In vitro angiogenesis was quantified by migration,
      mRNA levels of angiogenic genes, and endothelial tube formation. RESULTS: STP and
      SHMP dose dependently increased the proliferation and ALP activity and enhanced
      mineralized nodule formation and odontoblast marker mRNAs of HDPCs. STP and SHMP
      resulted in the up-regulation of angiogenic genes in HDPCs. Endothelial cells
      treated with conditioned medium collected from STP- and SHMP-exposed HDPCs showed
      an increase in migration and capillary tube formation. Knockdown of the
      expression of the genes encoding of inorganic pyrophosphate by small interfering
      RNA attenuated the STP- and SHMP-induced odontogenic differentiation and
      angiogenic potential. CONCLUSIONS: This study showed that STP and SHMP promote
      the growth, differentiation, and angiogenic potential of HDPCs. These results
      suggest that STP and SHMP may be candidates for dental pulp tissue engineering
      and regenerative endodontics.

PMID- 25777501
TI  - Vertical Bone Growth after Autotransplantation of Mature Third Molars: 2 Case
      Reports with Long-term Follow-up.
AB  - Tooth autotransplantation is a viable treatment option for tooth replacement when
      a suitable donor tooth is available. These case reports described significant
      vertical bone growth after autotransplantation of a mature third molar. The left
      mandible third molars (n = 2) were transplanted to the missing tooth in the left
      mandible. The patient follow-up period was 10 years after transplantation.
      Clinical examination revealed no mobility of the transplanted tooth. Radiographic
      examination indicated that bone regeneration occurred around the transplanted
      tooth. Vertical bone growth was observed in the cervical area of the root surface
      and the recipient bone. In autotransplantation of mature teeth, long-term follow
      up results indicate that vertical bone growth can be expected if viability of the
      periodontal ligament cells is maintained.

PMID- 25777502
TI  - Fracture strength of endodontically treated maxillary premolars supported by a
      horizontal glass fiber post: an in vitro study.
AB  - INTRODUCTION: The purpose of this study was to evaluate the effect of a
      horizontal glass fiber post on the fracture strength of endodontically treated
      maxillary premolars with mesioocclusaldistal (MOD) cavities. METHODS: Sixty
      extracted intact upper premolars were collected, treated endodontically (except
      for the control group), and divided into 5 test groups (n = 12) depending on the
      restoration type: G1 (control group, untreated teeth), G2 (MOD preparation
      without restoration), G3 (MOD preparation with resin composite restoration), G4
      (MOD preparation with resin composite restoration and a horizontal fiber post
      inserted between buccal and palatal walls), and G5 (MOD preparation with a
      horizontal fiber post only). The specimens were stored in normal saline at 37
      degrees C for 2 months. Then specimens were quasi-statically loaded in a
      universal testing machine until fracture occurred. Failure loads were then
      analyzed with one-way analysis of variance, followed by multiple comparisons by
      using Tukey honestly significant difference test (alpha = .05). The mode of
      failure was determined by visual inspection. RESULTS: Mean (standard deviation)
      failure loads for groups ranged from 411.8 N (+/-103.9) to 994.5 N (+/-147.3).
      One-way analysis of variance showed significant differences between fracture
      resistances of groups (P < .001). Tukey honestly significant difference test
      showed significant differences in fracture resistance within groups (P <= .05)
      except between the G1 (control group) and group G4 (P >= .05). All groups (except
      G4) had almost favorable fracture mode within the cervical third of the roots.
      CONCLUSIONS: Under the conditions of this in vitro study, a horizontal glass
      fiber post in a MOD cavity increased significantly the fracture resistance of the
      endodontically treated upper premolars.

PMID- 25777503
TI  - Geometric optimization for development of glide path preparation nickel-titanium
      rotary instrument.
AB  - INTRODUCTION: This study was done to develop a glide path preparation nickel
      titanium rotary instrument by size optimization procedures and evaluate the
      properties of the prototype. METHODS: G-1 and G-2 files were tested for cyclic
      fatigue, torsional resistance, and screw-in force. The cyclic fatigue resistance
      was compared by measuring the number of cycles to failure by using a 90 degrees 
      curved metal canal (n = 10). The torsional resistance was evaluated at 3 levels
      (2, 4, and 6 mm from the file tip) by measuring the ultimate torsional load (n =
      10 each level). The screw-in forces (n = 5) were measured during sequential
      pecking in a simulated resin block to the end of foramen by using the customized
      shaping device (AEndoS). Meanwhile, finite element models of G-1 and G-2 files
      were made by reverse engineering, and their bending stiffness and torsional
      properties were calculated. By analyzing the results from mechanical tests and
      finite element analysis, a universal G (uG) file was designed to have
      intermediary mechanical properties, and then the prototype was fabricated by the
      manufacturer. Cyclic fatigue and torsional resistance tests and screw-in force
      with the uG were compared with G-1 and G-2 files. RESULTS: The prototype of uG
      file showed higher cyclic fatigue resistance than the G-2 file and intermediary
      torsional strength and screw-in forces between the G-1 and G-2 files.
      CONCLUSIONS: The prototype production from a size optimization procedure produced
      appropriate mechanical properties for the purpose of development.

PMID- 25777504
TI  - Comparative study on the sensitivity of turions and active fronds of giant
      duckweed (Spirodela polyrhiza (L.) Schleiden) to heavy metal treatments.
AB  - Standard ecotoxicological test procedures use only active forms of aquatic
      plants. The potential effects of toxicants on vegetative propagules, which play
      an important role in the survival of several aquatic plant species, is not well
      understood. Because turion-like resting propagules overwinter on the water bottom
      in temperate regions, they could be exposed to contaminants for longer periods
      than active plants. Due to its turion producing capability, giant duckweed
      (Spirodela polyrhiza) is widely used in studying morphogenesis, dormancy, and
      activation mechanisms in plants. It is also suitable for ecotoxicological
      purposes. The present work aims to compare the growth inhibition sensitivity of
      active (normal frond) and overwintering (turion) forms of S. polyrhiza to
      concentrations of nickel (Ni), cadmium (Cd) and hexavalent chromium (Cr) ranging
      from 0 to 100mgL(-1). The results indicated that in general, resting turions have
      higher heavy metal tolerance than active fronds. Cd proved to be the most toxic
      heavy metal to S. polyrhiza active frond cultures because it induced rapid turion
      formation. In contrast, the toxicity of Ni and Cr were found to be similar but
      lower than the effects of Cd. Cr treatments up to 10mgL(-1) did not result in any
      future negative effects on turion activation. Turions did not survive heavy metal
      treatments at higher concentrations of Cr. Cd and Ni treatments affected both the
      floating-up and germination of turions but did not significantly affect the vigor
      of sprouts. Higher concentrations (of 100mgL(-1)) Cd completely inhibited
      germination. 

PMID- 25777505
TI  - Diagnostic performance of endocytoscopy for evaluating the invasion depth of
      different morphological types of colorectal tumors.
AB  - BACKGROUND AND AIM: Endocytoscopy (EC) is a next-generation endoscopic technique
      that enables diagnostic imaging at 450* magnification. In the present study, we
      retrospectively evaluated the diagnostic performance of EC and magnifying
      chromoendoscopy (MCE) for diagnosing the invasion depth of colorectal tumors.
      METHODS: We investigated 330 lesions with a >=10-mm tumor diameter that could be
      diagnosed by both MCE and EC. The lesions were classified according to
      morphological type as follows: laterally spreading type-granular (LST-G),
      laterally spreading type-non-granular (LST-NG), protruding, or depressed. After
      all lesions had been classified by both pit pattern and EC, qualitative and
      quantitative (invasion depth) diagnoses were made. The diagnostic accuracy was
      then compared between pit pattern classification and EC classification. RESULTS:
      Diagnostic accuracy of EC classification was significantly higher for LST-NG
      lesions (90.5%) than for protruding lesions (80.6%) (P < 0.05). Diagnostic
      accuracy for LST-NG lesions was significantly higher with EC classification
      (90.5%) than with pit pattern classification (79.3%) (P < 0.001). Comparison of
      the diagnostic performance of EC3a findings using EC classification between LST
      NG and protruding lesions revealed a sensitivity of 92.9% versus 11.3% (P <
      0.001), positive predictive value of 78.0% versus 27.3% (P < 0.001), negative
      predictive value of 95.5% versus 56.1% (P < 0.001), and diagnostic accuracy of
      87.9% versus 51.2% (P < 0.001), respectively. CONCLUSION: EC is a very useful
      method for evaluating the invasion depth of LST-NG lesions.

PMID- 25777506
TI  - Online dating among Australian gay and bisexual men: romance or hooking up?
AB  - Increasingly, gay and bisexual men (GBM) meet casual sex partners online and this
      has been associated with sexual risk behavior. How do GBM meet regular partners?
      This online anonymous survey of 4215 GBM included 2562 men with a primary regular
      partner (PRP) who were included in these analyses. Mean age of the sample was
      38.1 years. 60.3 % had met their PRP at least 2 years earlier. Meeting their PRP
      online increased from 14.0 % before 2001 to 79.9 % in 2013-2014. At all time
      points, men who met their PRP online were somewhat older than those who met their
      PRP offline. Regardless of how they met their PRP, most men met casual sex
      partners online. Among GBM, meeting sexual and romantic partners online has
      replaced other methods, for all age groups. The population of GBM who use the
      internet for this purpose is now equivalent to all sexually active GBM. 

PMID- 25777507
TI  - Examining Adherence Among Challenging Patients in Public and Private HIV Care in
      Argentina.
AB  - Treatment engagement, retention and adherence to care are required for optimal
      HIV outcomes. Yet, patients may fall below the treatment recommendations for
      achieving undetectable viral load or not be retained in care. This study examined
      the most challenging patients in Buenos Aires, Argentina, those non-adherent to
      HIV care. Men (n = 61) and women (n = 59) prescribed antiretrovirals (ARVs) and
      non-adherent to treatment in the prior 3-6 months were enrolled and assessed
      regarding adherence, knowledge, motivation and attitudes regarding treatment.
      Private clinic patients had lower viral load and higher self-reported adherence
      than public clinic patients. Motivations to be adherent and positive beliefs
      regarding ARVs were associated with increased adherence in public clinic
      participants. Increased self-efficacy was associated with increased adherence
      among participants from both clinics. Results support patient and provider
      interventions that strengthen the characteristics supporting adherence,
      engagement and retention in public and private clinic settings. 

PMID- 25777508
TI  - Depressive Symptoms Mediate the Effect of HIV-Related Stigmatization on
      Medication Adherence Among HIV-Infected Men Who Have Sex with Men.
AB  - This study tested the hypothesis that depressive symptoms would mediate the
      association of HIV-related stigma to medication adherence. We recruited HIV
      infected men who have sex with men (MSM; N = 66; 66 % White, 23 % African
      American) from an outpatient infectious disease clinic, and asked them to
      complete self-report measures. Mediational analyses showed that depressive
      symptoms fully mediated the association between HIV-related stigma and adherence.
      That is, stigma-related experiences were positively associated with depressive
      symptoms and negatively associated with adherence, and, in the final model,
      depressive symptoms remained a significant correlate of adherence while stigma
      did not. A test of the indirect effect of stigma on adherence through depressive
      symptoms was also significant (unstandardized b = -0.19; bootstrap 95 % CI -0.45
      to -0.01). These results highlight the importance of treating depressive symptoms
      in interventions aiming to improve medication adherence among HIV-infected MSM. 

PMID- 25777509
TI  - Expression of the glycolytic enzymes enolase and lactate dehydrogenase during the
      early phase of Toxoplasma differentiation is regulated by an intron retention
      mechanism.
AB  - The intracellular parasite Toxoplasma gondii converts from a rapidly replicating
      tachyzoite form during acute infection to a quiescent encysted bradyzoite stage
      that persists inside long-lived cells during chronic infection. Bradyzoites adopt
      reduced metabolism and slow replication while waiting for an opportunity to
      recrudesce the infection within the host. Interconversion between these two
      developmental stages is characterized by expression of glycolytic isoenzymes that
      play key roles in parasite metabolism. The parasite genome encodes two isoforms
      of lactate dehydrogenase (LDH1 and LDH2) and enolase (ENO1 and ENO2) that are
      expressed in a stage-specific manner. Expression of different isoforms of these
      enzymes allows T. gondii to rapidly adapt to diverse metabolic requirements
      necessary for either a rapid replication of the tachyzoite stage or a quiescent
      lifestyle typical of the bradyzoites. Herein we identified unspliced forms of LDH
      and ENO transcripts produced during transition between these two parasite stages
      suggestive of an intron retention mechanism to promptly exchange glycolytic
      isoforms for rapid adaptation to environmental changes. We also identified key
      regulatory elements in the ENO transcription units, revealing cooperation between
      the ENO2 5'-untranslated region and the ENO2 intron, along with identifying a
      role for the ENO1 3'-untranslated region in stage-specific expression. 

PMID- 25777512
TI  - Progranulin and Amyloid-beta Levels: Relationship to Neuropsychology in
      Frontotemporal and Alzheimer's Disease.
AB  - BACKGROUND: Analysis of cerebrospinal fluid (CSF) has improved over the last few
      years; thus specific markers for different diseases have emerged, e.g., amyloid
      beta (Abeta) for Alzheimer's disease (AD) and progranulin for frontotemporal
      dementia (FTD). OBJECTIVE: Evaluation of correlation between biomarkers in CSF
      and cognitive performance in populations with AD and FTD. METHODS: 27 patients
      with AD and 16 with FTD were included. CSF tau, P-tau(181P), Abeta42, and
      progranulin (PGRN) were measured and a standardized neuropsychological test
      battery applied. Olfactory testing was additionally included where available.
      RESULTS: For all patients across both groups, an association between PGRN and
      categoric (p = 0.016) and letter fluency (p = 0.029), naming (p = 0.003), and
      overall cognition (Mini-Mental State Examination: p = 0.04) was observed. Abeta42
      was strongly associated with memory function (learning: p = 0.001; recall: p =
      0.002). A correlation between Abeta42 and memory performance was moreover found
      for each group separately, while PGRN also showed a correlation with recognition
      memory (p = 0.04) in AD. Furthermore, an association between reduced PGRN and
      olfactory dysfunction was revealed (p = 0.01). CONCLUSIONS: CSF-levels of PGRN
      and Abeta42 levels express deficits in cognition differentially, with PGRN being
      predominantly associated with frontal and Abeta42 with temporal dysfunction. This
      mirrors the cerebral occurrence of these proteins. These associations appear to
      be consistent across both disease groups. The relationship between PGRN and
      olfaction further underpins the association between PRGN and frontal dysfunction.

PMID- 25777513
TI  - Do We Try Mending Humpty Dumpty or Prevent His Fall? An Alzheimer's Disease
      Dilemma.
AB  - In the popular nursery rhyme, Humpty Dumpty's great fall and the inability to put
      him together again has been used to demonstrate the second law of thermodynamics.
      An oversimplification of this law states that all things in the universe tend to
      move from order to disorder, an occurrence that can be applied allegorically to
      the development and clinical outcome of Alzheimer's disease (AD). An important
      argument relevant to the future use of resources and primary focus of AD research
      arises from the question, do we make it a priority to mend the shattered brain of
      AD patients or attempt to prevent the brain from shattering? If the former
      approach continues to be the priority it has become, how exactly do we mend the
      irreparable neuronal loss and associated cognitive failure in advanced cases of
      AD? Or, must we change direction and make prevention the primary goal of AD
      research? The latter approach would identify asymptomatic or mildly symptomatic
      patients with high risk of developing dementia by means of establishing
      multidisciplinary heart-brain clinics that would provide either close observation
      or a tailored therapeutic intervention. This is an important challenge that needs
      to be achieved if the AD incidence, societal costs and suffering, is to be
      significantly reduced. 

PMID- 25777514
TI  - The Continuing Failure of Bexarotene in Alzheimer's Disease Mice.
AB  - Alzheimer's disease (AD) is the most common form of dementia characterized by
      synaptic dysfunction, memory loss, neuroinflammation, and neuronal cell death.
      Amyloid-beta (Abeta), recognized as the main culprit of AD, aggregates and
      accumulates in the extracellular compartment as neuritic plaques, after
      deregulation of its production or clearance. Apolipoprotein E (ApoE) plays a
      major role in Abeta clearance and its expression is transcriptionally regulated
      by the liver X receptor and retinoid X receptors (RXRs) system. Bexarotene
      (BEXA), an RXR agonist that increases ApoE expression and microglia phagocytosis
      has been proposed as a promising therapy for AD, resolving both the amyloid
      pathology and memory loss. Despite the first compelling report, however, multiple
      failures have been documented, raising concern about whether BEXA could in fact
      become a novel disease-modifying strategy for AD. To help clarify this, we
      investigated the effect of BEXA in vivo at multiple levels in TASTPM transgenic
      mice. Seven-day oral administration of BEXA to these mice did not achieve any
      significant memory improvement, plaque reduction, or enhancement of microglial
      cell activation. No differences were found when specifically investigating the
      microglial phagocytic state in vivo. In addition, a brain structural analysis
      with magnetic resonance did not detect any BEXA-mediated change in the volume
      reduction of the main affected brain areas in our mice. These results suggest
      that BEXA has no beneficial effects on the multi-factorial pathologic phenotype
      of AD mice. 

PMID- 25777515
TI  - Traumatic Brain Injury, Chronic Traumatic Encephalopathy, and Alzheimer's
      Disease: Common Pathologies Potentiated by Altered Zinc Homeostasis.
AB  - Alzheimer's disease, traumatic brain injury, and chronic traumatic encephalopathy
      represent conditions that have a profound socioeconomic impact for both the
      individual and the wider community. They are all characterized by specific
      protein aggregation that results in synaptic dysfunction, neuronal death, and
      consequent cognitive decline and memory loss. In this review, we present evidence
      to support the notion that the common pathologies found in all conditions, and
      indeed their associated cognitive deficits, may be linked by zinc (Zn2+) ion
      dyshomeostasis. Elucidation of this hypothesis may present new therapeutic
      avenues for these devastating conditions.

PMID- 25777516
TI  - Correlates of Patient Retention in HIV Care and Treatment Programs in Nigeria.
AB  - BACKGROUND: Long-term retention is a crucial component of HIV care because
      treatment success can only be measured among retained patients. Understanding
      determinants of retention will inform retention strategies. We evaluated the
      correlates of retention in a large HIV program in Nigeria. METHODS: We reviewed
      quality of care data for 5320 randomly selected HIV-positive adults aged >=15
      years enrolled in 37 treatment facilities in Nigeria between 2005 and 2009.
      Retention was described as having one or more clinic visits in the one year
      (2010) review period. Patient-related correlates of retention were determined
      using logistic regression. RESULTS: 144 patients exited the program through
      deaths or transferrals. Of the 5176 with no documented exits, 3231 (62.4%) were
      retained (65.6% female; median age: 35.6 years). 2938 (75.8%) patients on ART,
      and 286 (23.4%) pre-ART patients were retained. Being on ART (OR=10.3, p<0.001),
      Age 30-60 years (30 - 45 years: OR=1.36, p<0.001 and >45 - 60 years: OR=1.47,
      p<0.001) compared to patients <30 years; Female gender (OR=1.18, p=0.006),
      baseline CD4 cell count (100-350 cells/mm(3): OR=1.24, p=0.006) vs <100
      cells/mm(3) and lower WHO stage at baseline (WHO Stage IV, III, II:
      OR=0.50,0.51,0.77 respectively) vs Stage I were associated with retention. Among
      patients on ART, recent ART initiation 2008-09 (OR=1.73, p<0.001) vs 2005-07,
      being on ART for >6 months (p<0.001) vs <6 month and initiating ART on non
      Stavudine based regimen (p<0.001) were also associated with retention.
      CONCLUSION: 3 out of 4 pre-ART patients and 1-in-4 ART patients were not retained
      in 37 HIV treatment facilities in Nigeria. These findings provide insight that
      enables HIV programs integrate retention strategies at all stages of the HIV care
      continuum.

PMID- 25777517
TI  - Meta-analysis and time series modeling allow a systematic review of primary HIV-1
      drug-resistant prevalence in Latin America and Caribbean.
AB  - Here we review the prevalence of HIV-1 primary drug resistance in Latin America
      and Caribbean using meta-analysis as well as time-series modeling. We also
      discuss whether there could be a drawback to HIV/AIDS programs due to drug
      resistance in Latin America and Caribbean in the next years. We observed that,
      although some studies report low or moderate primary drug resistance prevalence
      in Caribbean countries, this evidence needs to be updated. In other countries,
      such as Brazil and Argentina, the prevalence of drug resistance appears to be
      rising. Mutations conferring resistance against reverse transcriptase inhibitors
      were the most frequent in the analyzed populations (70% of all mutational
      events). HIV-1 subtype B was the most prevalent in Latin America and the
      Caribbean, although subtype C and B/F recombinants have significant contributions
      in Argentina and Brazil. Thus, we suggest that primary drug resistance in Latin
      America and the Caribbean could have been underestimated. Clinical monitoring
      should be improved to offer better therapy, reducing the risk for HIV-1
      resistance emergence and spread, principally in vulnerable populations, such as
      men who have sex with men transmission group, sex workers and intravenous drug
      users. 

PMID- 25777518
TI  - The ultrastructure of the book lungs of the Italian trap-door spider Cteniza sp.
      (Araneae, Mygalomorphae, Ctenizidae).
AB  - The fine structure of book lungs is not homogeneous across Arachnids and is
      considered phylogenetically informative, however few reports on the
      ultrastructural features of this organ have been published. In this study, we
      examined the general morphology and ultrastructure of adult spiders of the genus
      Cteniza. The respiratory system of Cteniza sp. consists of two pairs of well
      developed book lungs, which is considered indicative of primitive spiders. The
      general organization of the book lungs is similar to that described for other
      arachnids and consists of leaves of alternating air and hemolymph channels. The
      air channels are lined with cuticle and open to an atrium that leads to a slit
      like spiracle. The air channels are held open by cuticular trabeculae. The space
      holders in the hemolymph channels are pillar trabeculae formed by two cells from
      the opposed walls. The pillar cells have a complex ultrastructure that includes
      an interdigitating connection, gap junctions, microtubules and hemidesmosomes.
      These features apparently help strengthen the pillar cells and their
      interconnections with each other and the underlying cuticle. The cytoskeleton
      resembles that of arthropod tendon cells where substantial structural support is
      needed. 

PMID- 25777519
TI  - Zirconocene-catalyzed sequential ethylcarboxylation of alkenes using
      ethylmagnesium chloride and carbon dioxide.
AB  - The zirconocene-catalyzed sequential ethylcarboxylation of alkenes using
      ethylmagnesium chloride and carbon dioxide has been developed. A range of alkenes
      were transformed into the corresponding carboxylic acids in high yields. 

PMID- 25777520
TI  - Demyelination syndrome due to rapid correction of desmopressin-associated
      hyponatremia in a known case of central diabetes insipidus: a case report.

PMID- 25777521
TI  - Endovascular thrombectomy followed by decompressive surgery in a patient with
      cerebral venous sinus thrombosis (CVST).

PMID- 25777522
TI  - Galantamine improves sleep quality in patients with dementia.
AB  - The purpose of the study was to evaluate the influences of cholinesterase
      inhibitors on sleep pattern and sleep disturbance. A total of 87 mild to moderate
      stage dementia patients who were not on cholinesterase enzyme inhibitor and
      memantine treatment were included in the study. The dementia patients were
      treated with donepezil, galantamine or rivastigmine, depending on the preference
      of the clinician. Fifty-five dementia patients (63.2 %) completed the study.
      Twenty-three elderly subjects, who had normal cognitive functions, were included
      in the study as the control group. The Pittsburgh Sleep Quality Index was used
      for evaluating the sleep quality at the beginning and at the final assessment.
      The improvement in sleep quality was better with regard to changes in Pittsburgh
      Sleep Quality Index scores with galantamine treatment compared to the donepezil
      and the control groups. A significant decrease in Pittsburgh Sleep Quality Index
      scores was detected in the galantamine group after treatment. Although
      statistically not significant, rivastigmine decreased and donepezil increased the
      Pittsburgh Sleep Quality Index scores after treatment. Dementia patients who had
      a poor sleep quality (n: 36), the rate of improvement in sleep disturbance was
      81.8 % in the galantamine group, 75 % in the rivastigmine, and 50 % in the
      donepezil group. Galantamine may be the first choice of cholinesterase inhibitor
      in mild to moderate dementia patients in terms of improving sleep quality.

PMID- 25777523
TI  - Computational approaches towards understanding human long non-coding RNA biology.
AB  - Long non-coding RNAs (lncRNAs) form the largest class of non-protein coding genes
      in the human genome. While a small subset of well-characterized lncRNAs has
      demonstrated their significant role in diverse biological functions like
      chromatin modifications, post-transcriptional regulation, imprinting etc., the
      functional significance of a vast majority of them still remains an enigma.
      Increasing evidence of the implications of lncRNAs in various diseases including
      cancer and major developmental processes has further enhanced the need to gain
      mechanistic insights into the lncRNA functions. Here, we present a comprehensive
      review of the various computational approaches and tools available for the
      identification and annotation of long non-coding RNAs. We also discuss a
      conceptual roadmap to systematically explore the functional properties of the
      lncRNAs using computational approaches.

PMID- 25777524
TI  - WGBSSuite: simulating whole-genome bisulphite sequencing data and benchmarking
      differential DNA methylation analysis tools.
AB  - MOTIVATION: As the number of studies looking at differences between DNA
      methylation increases, there is a growing demand to develop and benchmark
      statistical methods to analyse these data. To date no objective approach for the
      comparison of these methods has been developed and as such it remains difficult
      to assess which analysis tool is most appropriate for a given experiment. As a
      result, there is an unmet need for a DNA methylation data simulator that can
      accurately reproduce a wide range of experimental setups, and can be routinely
      used to compare the performance of different statistical models. RESULTS: We have
      developed WGBSSuite, a flexible stochastic simulation tool that generates single
      base resolution DNA methylation data genome-wide. Several simulator parameters
      can be derived directly from real datasets provided by the user in order to mimic
      real case scenarios. Thus, it is possible to choose the most appropriate
      statistical analysis tool for a given simulated design. To show the usefulness of
      our simulator, we also report a benchmark of commonly used methods for
      differential methylation analysis. AVAILABILITY AND IMPLEMENTATION: WGBS code and
      documentation are available under GNU licence at http://www.wgbssuite.org.uk/
      CONTACT: : owen.rackham@imperial.ac.uk or l.bottolo@imperial.ac.uk SUPPLEMENTARY
      INFORMATION: Supplementary data are available at Bioinformatics online.

PMID- 25777525
TI  - Cardinal: an R package for statistical analysis of mass spectrometry-based
      imaging experiments.
AB  - Cardinal is an R package for statistical analysis of mass spectrometry-based
      imaging (MSI) experiments of biological samples such as tissues. Cardinal
      supports both Matrix-Assisted Laser Desorption/Ionization (MALDI) and Desorption
      Electrospray Ionization-based MSI workflows, and experiments with multiple
      tissues and complex designs. The main analytical functionalities include (1)
      image segmentation, which partitions a tissue into regions of homogeneous
      chemical composition, selects the number of segments and the subset of
      informative ions, and characterizes the associated uncertainty and (2) image
      classification, which assigns locations on the tissue to pre-defined classes,
      selects the subset of informative ions, and estimates the resulting
      classification error by (cross-) validation. The statistical methods are based on
      mixture modeling and regularization.

PMID- 25777526
TI  - Probing the binding affinity of amyloids to reduce toxicity of oligomers in
      diabetes.
AB  - MOTIVATION: Amyloids play a role in the degradation of beta-cells in diabetes
      patients. In particular, short amyloid oligomers inject themselves into the
      membranes of these cells and create pores that disrupt the strictly controlled
      flow of ions through the membranes. This leads to cell death. Getting rid of the
      short oligomers either by a deconstruction process or by elongating them into
      longer fibrils will reduce this toxicity and allow the beta-cells to live longer.
      RESULTS: We develop a computational method to probe the binding affinity of
      amyloid structures and produce an amylin analog that binds to oligomers and
      extends their length. The binding and extension lower toxicity and beta-cell
      death. The amylin analog is designed through a parsimonious selection of
      mutations and is to be administered with the pramlintide drug, but not to
      interact with it. The mutations (T9K L12K S28H T30K) produce a stable native
      structure, strong binding affinity to oligomers, and long fibrils. We present an
      extended mathematical model for the insulin-glucose relationship and demonstrate
      how affecting the concentration of oligomers with such analog is strictly coupled
      with insulin release and beta-cell fitness. AVAILABILITY AND IMPLEMENTATION:
      SEMBA, the tool to probe the binding affinity of amyloid proteins and generate
      the binding affinity scoring matrices and R-scores is available at:
      http://amyloid.cs.mcgill.ca

PMID- 25777527
TI  - SOMP: web server for in silico prediction of sites of metabolism for drug-like
      compounds.
AB  - A new freely available web server site of metabolism predictor to predict the
      sites of metabolism (SOM) based on the structural formula of chemicals has been
      developed. It is based on the analyses of 'structure-SOM' relationships using a
      Bayesian approach and labelled multilevel neighbourhoods of atoms descriptors to
      represent the structures of over 1000 metabolized xenobiotics. The server allows
      predicting SOMs that are catalysed by 1A2, 2C9, 2C19, 2D6 and 3A4 isoforms of
      cytochrome P450 and enzymes of the UDP-glucuronosyltransferase family. The
      average invariant accuracy of prediction that was calculated for the training
      sets (using leave-one-out cross-validation) and evaluation sets is 0.9 and 0.95,
      respectively. AVAILABILITY AND IMPLEMENTATION: Freely available on the web at
      http://www.way2drug.com/SOMP.

PMID- 25777528
TI  - X-ray and Cryo-EM structures reveal mutual conformational changes of Kinesin and
      GTP-state microtubules upon binding.
AB  - The molecular motor kinesin moves along microtubules using energy from ATP
      hydrolysis in an initial step coupled with ADP release. In neurons, kinesin
      1/KIF5C preferentially binds to the GTP-state microtubules over GDP-state
      microtubules to selectively enter an axon among many processes; however, because
      the atomic structure of nucleotide-free KIF5C is unavailable, its molecular
      mechanism remains unresolved. Here, the crystal structure of nucleotide-free
      KIF5C and the cryo-electron microscopic structure of nucleotide-free KIF5C
      complexed with the GTP-state microtubule are presented. The structures illustrate
      mutual conformational changes induced by interaction between the GTP-state
      microtubule and KIF5C. KIF5C acquires the 'rigor conformation', where mobile
      switches I and II are stabilized through L11 and the initial portion of the neck
      linker, facilitating effective ADP release and the weak-to-strong transition of
      KIF5C microtubule affinity. Conformational changes to tubulin strengthen the
      longitudinal contacts of the GTP-state microtubule in a similar manner to GDP
      taxol microtubules. These results and functional analyses provide the molecular
      mechanism of the preferential binding of KIF5C to GTP-state microtubules. 

PMID- 25777529
TI  - Error-free and mutagenic processing of topoisomerase 1-provoked damage at genomic
      ribonucleotides.
AB  - Genomic ribonucleotides incorporated during DNA replication are commonly repaired
      by RNase H2-dependent ribonucleotide excision repair (RER). When RNase H2 is
      compromised, such as in Aicardi-Goutieres patients, genomic ribonucleotides
      either persist or are processed by DNA topoisomerase 1 (Top1) by either error
      free or mutagenic repair. Here, we present a biochemical analysis of these
      pathways. Top1 cleavage at genomic ribonucleotides can produce ribonucleoside
      2',3'-cyclic phosphate-terminated nicks. Remarkably, this nick is rapidly
      reverted by Top1, thereby providing another opportunity for repair by RER.
      However, the 2',3'-cyclic phosphate-terminated nick is also processed by Top1
      incision, generally 2 nucleotides upstream of the nick, which produces a covalent
      Top1-DNA complex with a 2-nucleotide gap. We show that these covalent complexes
      can be processed by proteolysis, followed by removal of the phospho-peptide by
      Tdp1 and the 3'-phosphate by Tpp1 to mediate error-free repair. However, when the
      2-nucleotide gap is associated with a dinucleotide repeat sequence, sequence
      slippage re-alignment followed by Top1-mediated religation can occur which
      results in 2-nucleotide deletion. The efficiency of deletion formation shows
      strong sequence-context dependence. 

PMID- 25777530
TI  - Graphene-based nanomaterials for versatile imaging studies.
AB  - Over the last decade, interest in graphene has surged because of its
      unprecedented physical, chemical, electrical, and mechanical properties. In
      recent years, researchers' interests have gradually shifted to other notable
      properties of graphene - its environmentally-friendly nature with outstanding
      optical properties. Thus, graphene is considered to be a promising and attractive
      candidate for various biomedical applications such as NIR-responsive cancer
      therapy and fluorescence bio-imaging. To that end, appropriate preparation and
      novel approaches to utilize graphene-based materials such as graphene oxides
      (GOs), reduced graphene oxides (rGOs), and graphene quantum dots (GQDs) in
      biology and medical science are gaining growing interest. In this review, we
      highlight recent applications of graphene-based materials as novel prospects for
      versatile imaging studies with a brief perspective on their future applications. 

PMID- 25777532
TI  - Dissolution enhancement of felodipine by amorphous nanodispersions using an
      amphiphilic polymer: insight into the role of drug-polymer interactions on drug
      dissolution.
AB  - CONTEXT: Felodipine, a poorly soluble drug, is widely used in the treatment of
      angina pectoris and hypertension. OBJECTIVE: This study aimed at the preparation
      of amorphous solid dispersion (SD) of felodipine using an amphiphilic polymer,
      soluplus, for the potential enhancement in solubility of the drug. MATERIALS AND
      METHODS: Solid dispersions with varying proportions of drug and soluplus were
      prepared and the rate and extent of dissolution from SDs was compared with that
      of the pure drug. FT-IR and (1)H NMR spectroscopic analysis were carried out to
      examine the formation mechanism of SDs. Various techniques were used for solid
      state characterization of designed SDs. RESULTS: Formation of amorphous solid
      dispersions with particle size in nanometer range indicated suitability of
      polymer and method used in the preparation. FT-IR and (1)H NMR spectroscopy
      revealed that soluplus was involved in strong hydrogen bonding with felodipine
      molecules which resulted in the conversion of crystalline felodipine into
      amorphous form. Solid dispersion with 1:10 drug/polymer ratio showed more than
      90% drug dissolution in 30 min whereas pure felodipine showed less than 19% drug
      dissolution in 1 h. DISCUSSION AND CONCLUSION: Amorphous SDs of felodipine were
      prepared using soluplus resulting in substantial enhancement in the rate and
      extent of dissolution of felodipine.

PMID- 25777531
TI  - Neuroprotective effects of activated protein C on intrauterine inflammation
      induced neonatal white matter injury are associated with the downregulation of
      fibrinogen-like protein 2/fibroleukin prothrombinase and the inhibition of pro
      inflammatory cytokine expression.
AB  - Maternal intrauterine inflammation or infection is an important risk factor for
      neonatal cerebral white matter injury (WMI) and future neurological deficits.
      Activated protein C (APC), a natural anticoagulant, has been shown to exhibit
      anti-inflammatory, anti-apoptotic, profibrinolytic and cytoprotective activities.
      Recent studies have demonstrated that the novel prothrombinase, fibrinogen-like
      protein 2 (fgl2), contributes to the pathogenesis of a number of inflammatory
      diseases through the generation of fibrin. Thus, we hypothesized that APC may
      regulate coagulant and inflammatory processes and improve brain injury in an
      experimental rat model of intrauterine inflammation-induced WMI. The animal model
      was established by the administration of an intraperitoneal injection of
      lipopolysaccharide (LPS) to pregnant Sprague-Dawley rats on embryonic day (E)17
      and E18. APC was administered intraperitoneally 30 min after the second LPS
      injection. The expression of fgl2 and the pro-inflammatory cytokines, tumor
      necrosis factor-alpha (TNF-alpha), interleukin (IL)-6 and IL-1beta expression in
      the placentas and fetal brains was determined on E19. Nerve cell death, the brain
      water content and protease-activated receptor 1 (PAR1) and nuclear factor kappaB
      (NF-kappaB) p65 expression was detected in the fetal brains. WMI in the neonatal
      rat brains was evaluated by hematoxylin and eosin (H&E) staining and
      immunohistochemistry for myelin basic protein (MBP). The results revealed that
      APC markedly reduced the LPS-induced increase in fgl2 expression and fibrin
      deposition, as well as the production of the pro-inflammatory cytokines, TNF
      alpha, IL-6 and IL-1beta, in the placentas and fetal brains. In addition, APC
      attenuated cerebral apoptosis and brain edema, downregulated PAR1 and NF-kappaB
      p65 expression in the fetal brains, and improved hypomyelination and structural
      disturbances in the periventricular area of the neonatal rat brains. Our
      observations provide evidence that APC attenuates fetal neuroinflammation and the
      associated secondary WMI in the developing brain by inhibiting the expression of
      fgl2 and pro-inflammatory mediators, suggesting that APC may be a potential
      therapeutic approach for intrauterine inflammation-induced neonatal brain injury.

PMID- 25777533
TI  - Differential expression of TOX by skin-infiltrating T cells in Sezary syndrome
      and erythrodermic dermatitis.
AB  - BACKGROUND: The histopathologic differentiation between Sezary syndrome (SS) and
      erythrodermic dermatitis may be extremely difficult. In this immunohistochemical
      study, it was investigated if thymocyte selection-associated high mobility group
      box protein (TOX) and C-MYC can be used as additional diagnostic markers to
      differentiate between SS and erythrodermic dermatitis. METHOD: Paraffin-embedded
      skin biopsies from 15 SS patients and 17 erythrodermic dermatitis patients were
      stained and scored for TOX or C-MYC expression. RESULTS: Strong nuclear staining
      for TOX in more than 50% of skin-infiltrating T cells was observed in 13 of 15
      (87%) SS cases, whereas erythrodermic dermatitis cases showed weak nuclear
      staining in 11-50% (median: 25%) of the T cells; strong nuclear staining as found
      in SS was never observed in erythrodermic dermatitis. No significant differences
      in C-MYC expression between SS and erythrodermic dermatitis were found. In most
      patients of both groups, percentages of C-MYC positive-cells varied between less
      than 10 and 25% of skin-infiltrating T cells. CONCLUSION: Our results suggest
      that strong expression of TOX in more than 50% of skin-infiltrating T cells in
      erythrodermic skin is a useful marker in the differentiation between SS and
      erythrodermic dermatitis, whereas staining for C-MYC does not contribute to
      differential diagnosis.

PMID- 25777535
TI  - Expert's comment concerning Grand Rounds case entitled "Scoliosis correction
      surgery for patients with McCune-Albright syndrome using pedicle screws: a report
      of two cases with different characteristics and a review of the literature" (K.
      Yamane, M. Tanaka, Y. Sugimoto, H. Misawa and T. Ozaki).

PMID- 25777536
TI  - Vertebral body fracture following stand-alone lateral lumbar interbody fusion
      (LLIF): report of two events out of 712 levels.
AB  - PURPOSE: Available studies demonstrate vertebral body fractures as a relatively
      rare complication following lateral lumbar interbody fusion (LLIF), with most
      fractures reported in association with lateral plating and vertebral screws. This
      study reports the occurrence of two vertebral body fractures following stand
      alone LLIF in 712 levels fused in 335 patients. METHODS: A retrospective review
      of prospectively collected data was performed on all patients who underwent
      minimally invasive LLIF over a seven-year period at a single institution.
      Patients with vertebral body fractures were recorded. RESULTS: Two patients (0.6
      %) out of 335 total patients (712 levels) were identified with vertebral body
      fractures following stand-alone LLIF. Both patients presented with severe back
      pain and return of symptoms within 2 weeks of the index surgery. Both patients
      were obese, had impaired bone mineral density and were managed with open
      posterior segmental fixation. CONCLUSIONS: The 0.6 % incidence of vertebral body
      fractures in our series of fusing 712 levels is in accordance with the incidence
      rates reported in the literature. Potential risk factors for vertebral body
      fractures at the index LLIF level included obesity, osteopenia, unrecognized
      intraoperative endplate breach, graft subsidence and oversized graft placement.

PMID- 25777537
TI  - A visual and organic vapor sensitive photonic crystal sensor consisting of
      polymer-infiltrated SiO2 inverse opal.
AB  - A photonic crystal (PC) sensor that can selectively detect organic vapors through
      visual color changes has been proposed. The sensor was fabricated by infiltrating
      a tetraphenylethene polymer (TPEP) into the voids of SiO2 inverse opal photonic
      crystal. When the sensor was exposed to tetrahydrofuran or acetone vapor, a red
      shift of the stopband of more than 50 nm could be clearly observed; meanwhile,
      the film's color changed from violet to cyan. Subsequently, when exposed to air,
      the stopband underwent a blue shift and the color returned to violet. The reason
      for the observed change is that a reversible adsorption-desorption process occurs
      on alternate exposure of the sensor to organic vapor and air, due to the high
      specific surface area of the inverse opal macroporous structure and the high
      affinity of TPEP to tetrahydrofuran and acetone. The adsorption of vapor analyte
      can increase the PC's effective refractive index, which will induce the stopband
      red shift and the resulting color change according to Bragg's Law. The reversible
      adsorption-desorption of organic vapors varied the effective refractive index of
      the sensor repeatedly, causing the reversible stopband shift and color change,
      and providing a general method for the design of visual vapor sensors. 

PMID- 25777538
TI  - Effect of 1,25-dihydroxyvitamin D3 on the Wnt pathway in non-malignant colonic
      cells.
AB  - Epidemiological studies suggest a correlation between vitamin D deficiency and
      colorectal cancer (CRC) incidence. The majority of sporadic tumors develop from
      premalignant lesions with aberrant activation of the Wnt/beta-catenin signaling
      pathway. The adenoma cell line LT97 harbors an adenomatous polyposis coli (APC)
      mutation leading to constitutively active Wnt signaling. In these cells,
      expression of Wnt target genes leads to increased survival capacity. We
      hypothesized that 1,25-dihydroyvitamin D3 (1,25-D3), the active form of vitamin
      D3, promotes differentiation by modulating beta-catenin/T-cell factor (TCF) 4
      mediated gene transcription. The effect of dietary vitamin D on colonic Wnt
      signaling was investigated in mice fed either with 100 IU or 2500 IU vitamin D/kg
      diet. We examined the effect of 1,25-D3 on differentiation by measuring alkaline
      phosphatase activity. We analyzed mRNA expression of Wnt target genes by real
      time qRT-PCR. The impact of 1,25-D3 on beta-catenin and TCF4 protein expression
      was assessed by western blot and immunohistochemistry. In LT97 cells, 1,25-D3
      increased cellular differentiation and reduced nuclear beta-catenin levels.
      Further, 1,25-D3 decreased mRNA expression of the Wnt target genes BCL-2, Cyclin
      D1, Snail1, CD44 and LGR5. In healthy colon of mice fed with high vitamin D diet,
      the mRNA levels of Wnt5a and ROR2, that promote degradation of beta-catenin, were
      upregulated whereas beta-catenin and TCF4 protein expression were decreased. In
      conclusion, 1,25-D3 inhibits Wnt signaling even in nonmalignant cells underlining
      its importance in protection against colorectal tumorigenesis and early tumor
      progression. This article is part of a Special Issue entitled '17th Vitamin D
      Workshop'.

PMID- 25777539
TI  - Somatostatin prevents lipopolysaccharide-induced neurodegeneration in the rat
      substantia nigra by inhibiting the activation of microglia.
AB  - Somatostatin (SST) is a neuromodulator which is abundant throughout the central
      nervous system (CNS) and has a crucial role in neurodegenerative disorders.
      However, little is known about the effects and mechanisms of SST in dopaminergic
      (DA) neurons in the context of Parkinson's disease (PD). In the present study, a
      model of PD was generated by injecting lipopolysaccharide (LPS) into the
      substantia nigra (SN) of rats in order to investigate the effects of SST on LPS
      induced degeneration of DA in vivo. Intramural injection of LPS resulted in a
      significant loss of DA neurons, while reduction of neuronal death by SST
      pretreatment was confirmed using immunohistochemical staining for tyrosine
      hydroxylase and Nissl. In parallel, immunohistochemical detection of OX-42 and
      hydroethidine staining were employed to determine the activation of microglia and
      production of reactive oxygen species (ROS), respectively. It was found that SST
      inhibited the LPS-induced microglial activity and ROS production. ELISA revealed
      a decreased production of pro-inflammatory mediators, including tumor necrosis
      factor-alpha, interleukin-1beta and prostaglandin E2 when SST was administered
      prior to LPS treatment. Western blot analysis showed that LPS-induced expression
      of inducible nitric oxide synthase, cyclooxygenase-2 and nuclear factor kappaB
      (NF-kappaB) p-p65 was attenuated by administration of SST prior to LPS
      application. The results indicated that LPS-induced loss of nigral DA neurons was
      inhibited by SST and the observed effects of SST on neuroprotection were
      associated with suppression of microglial activation and the NF-kappaB pathway,
      ensuing decreases of neuroinflammation and oxidative stress. The present study
      therefore suggested that SST is beneficial for treating neurodegenerative
      diseases, such as PD, through inhibiting the activation of microglia.

PMID- 25777540
TI  - Mapping motion of antiferromagnetic interfacial uncompensated magnetic moment in
      exchange-biased bilayers.
AB  - In this work, disordered-IrMn3/insulating-Y3Fe5O12 exchange-biased bilayers are
      studied. The behavior of the net magnetic moment DeltamAFM in the antiferromagnet
      is directly probed by anomalous and planar Hall effects, and anisotropic
      magnetoresistance. The DeltamAFM is proved to come from the interfacial
      uncompensated magnetic moment. We demonstrate that the exchange bias and
      rotational hysteresis loss are induced by partial rotation and irreversible
      switching of the DeltamAFM. In the athermal training effect, the state of the
      DeltamAFM cannot be recovered after one cycle of hysteresis loop. This work
      highlights the fundamental role of the DeltamAFM in the exchange bias and
      facilitates the manipulation of antiferromagnetic spintronic devices. 

PMID- 25777541
TI  - Reply to: Heinz bodies and erythrophagocytosis in the peripheral blood of
      loggerhead sea turtles.

PMID- 25777544
TI  - Specific ion effects on particle aggregation induced by monovalent salts within
      the Hofmeister series.
AB  - Ion specific effects of monovalent salts on charging and aggregation for two
      types of polystyrene latex particles were investigated by electrophoresis and
      time-resolved light scattering. The chemical composition of the electrolytes was
      systematically varied in the experiments. Accordingly, NaH2PO4, NaF, NaCl, NaBr,
      NaNO3, and NaSCN were used to vary the anions and N(CH3)4Cl, NH4Cl, CsCl, KCl,
      NaCl, and LiCl for the cations. The salt concentration dependence of the
      electrophoretic mobilities indicates that the surface charge was screened by the
      counterions when their concentrations increased. For the SCN(-) ions, adsorption
      on positively charged particles leads to charge reversal. The aggregation rates
      are small at low electrolyte concentrations indicating stable dispersions under
      these conditions, and they increase with the salt concentration. When viscosity
      corrections are taken into account, no ion specific effects in the fast
      aggregation regime can be established. The slow and fast aggregation regimes are
      separated by the critical coagulation concentration (CCC). Within the
      experimental error, the CCCs are the same in systems containing different co-ions
      but the same counterions, with the exception of ammonium salts. However, the
      variation of counterions leads to different CCC values due to specific
      interaction of the counterions with the surface. These values follow the
      Hofmeister series for negatively charged sulfate latex particles, while the
      reversed order was observed for positively charged amidine latex. Comparison
      between experimental CCCs and those calculated by the theory of Derjaguin,
      Landau, Verwey, and Owerbeek reveals that variations in the surface charge due to
      ionic adsorption are mainly responsible for the ion specific effects in the
      aggregation process. 

PMID- 25777542
TI  - Association between individual and combined SNPs in genes related to innate
      immunity and incidence of CMV infection in seropositive kidney transplant
      recipients.
AB  - In this study, we assessed the association between single-nucleotide
      polymorphisms (SNPs) in seven candidate genes involved in orchestrating the
      immune response against cytomegalovirus (CMV) and the 12-month incidence of CMV
      infection in 315 CMV-seropositive kidney transplant (KT) recipients. Patients
      were managed either by antiviral prophylaxis or preemptive therapy. CMV infection
      occurred in 140 patients (44.4%), including 13 episodes of disease. After
      adjusting for various clinical covariates, patients harboring T-allele genotypes
      of interleukin-28B (IL28B) (rs12979860) SNP had lower incidence of CMV infection
      (adjusted hazard ratio [aHR]: 0.66; 95% confidence interval [CI]: 0.46-0.96; p
      value = 0.029). In the analysis restricted to patients not receiving prophylaxis,
      carriers of the TT genotype of toll-like receptor 9 (TLR9) (rs5743836) SNP had
      lower incidence of infection (aHR: 0.61; 95% CI: 0.38-0.96; p-value = 0.035),
      whereas the GG genotype of dendritic cell-specific ICAM 3-grabbing nonintegrin
      (DC-SIGN) (rs735240) SNP exerted the opposite effect (aHR: 1.86; 95% CI: 1.18
      2.94; p-value = 0.008). An independent association was found between the number
      of unfavorable SNP genotypes carried by the patient and the incidence of CMV
      infection. In conclusion, specific SNPs in IL28B, TLR9 and DC-SIGN genes may play
      a role in modulating the susceptibility to CMV infection in CMV-seropositive KT
      recipients. 

PMID- 25777545
TI  - Comparative safety study on severe anemia by simeprevir versus telaprevir-based
      triple therapy for chronic hepatitis C.
AB  - BACKGROUND AND AIM: The addition of hepatitis C virus (HCV) NS3/4A protease
      inhibitors to the pegylated interferon (PEG-IFN) alpha and ribavirin combination
      regimen (triple therapy) has dramatically improved treatment outcome.
      Unfortunately, anemia remains a common adverse effect. This study was done to
      compare the development of severe anemia during simeprevir- or telaprevir-based
      triple therapy. METHODS: This retrospective multicenter study consisted of 837
      consecutive Japanese HCV genotype 1 patients treated in a real-world clinical
      setting, 811 of whom were enrolled (simeprevir 281, telaprevir 530). The inosine
      triphosphate pyrophosphatase (ITPA) genotype at rs1127354 was determined for all
      studied patients. Logistic regression was done after propensity score matching to
      assess the risk of development of severe anemia. RESULTS: Propensity score
      matching of the entire study population yielded 266 matched pairs. Severe anemia
      (nadir hemoglobin < 9.0 g/dL) was developed during the treatment period by 81
      (30.5%) and 144 (54.1%) patients treated with simeprevir and telaprevir,
      respectively. Treatment with simeprevir was independently associated with a lower
      risk of severe anemia (odds ratio 0.25, 95% confidence interval 0.16-0.38, P <
      0.0001). Moreover, ITPA genotype, age, hemoglobin level, and estimated glomerular
      filtration rate at baseline were also independent factors associated with the
      development of severe anemia. CONCLUSIONS: Patients treated with simeprevir-based
      triple therapy have a lower risk of the development of severe anemia than those
      treated with telaprevir. Moreover, ITPA genotype and age may be useful for
      individualizing treatment to reduce the risk of anemia-related adverse effects.

PMID- 25777546
TI  - Randomized, Double-Blind, Placebo-Controlled Trial of the Effect of Vitamin D3 on
      the Interferon Signature in Patients With Systemic Lupus Erythematosus.
AB  - OBJECTIVE: Vitamin D modulates the immune response and blocks induction of an
      interferon (IFN) signature by systemic lupus erythematosus (SLE) sera. This study
      was undertaken to investigate the effects of vitamin D supplementation on the IFN
      signature in patients with SLE. METHODS: SLE patients (n = 57) with stable,
      inactive disease, a serum 25-hydroxyvitamin D (25[OH]D) level <=20 ng/ml, an
      elevated anti-double-stranded DNA antibody level, and an IFN signature (as
      determined by measuring the expression levels of 3 IFN response genes) were
      randomized into a 12-week double-blind, placebo-controlled trial of vitamin D3 at
      doses of 2,000 IU or 4,000 IU. An IFN signature response was defined as a 50%
      reduction in the expression of 1 of the 3 genes or a 25% reduction in the
      expression of 2 of the 3 genes. Disease activity, adverse events, and endocrine
      effects were assessed. RESULTS: Baseline characteristics of the patients in the 3
      treatment groups (placebo, low-dose vitamin D3 , or high-dose vitamin D3 ) were
      similar. Repletion of 25(OH)D (i.e., levels >=30 ng/ml) was not observed in any
      of the patients who were receiving placebo, while repletion was observed in 16 of
      33 patients receiving vitamin D3 . The percentage of patients with an IFN
      signature response did not differ among the treatment groups. Moreover, there was
      no difference in the percentage of patients with an IFN signature response
      between those who remained vitamin D deficient and those who demonstrated
      repletion of vitamin D. Modular microarray analysis of a subset of patients (n =
      40) did not reveal changes from baseline in any modules (including the IFN
      inducible module) in any of the treatment groups, and no differences in
      expression were found between patients who demonstrated vitamin D repletion and
      patients who were persistently vitamin D deficient. Vitamin D3 was well
      tolerated, and there were no safety concerns. CONCLUSION: Vitamin D3
      supplementation up to 4,000 IU daily was safe and well-tolerated but failed to
      diminish the IFN signature in vitamin D-deficient SLE patients. Higher 25(OH)D
      levels sustained for a longer duration may be required to affect immunologic
      outcomes.

PMID- 25777548
TI  - Well, I'm healthy, but...--lay perspectives on health among people with
      musculoskeletal disorders.
AB  - PURPOSE: The purpose was to investigate lay perspectives on health among people
      with musculoskeletal disorders. METHOD: Semi-structured interviews were performed
      with 39 women and 30 men, (aged 22-63 years) with long-term, non-specific
      musculoskeletal disorders in the neck, shoulder and/or low back. Data was
      analysed using qualitative content analysis. RESULTS: These people experienced
      health as "having resources and opportunities to lead the life one wants". Three
      categories, "a good enough physical and psychological functioning, freedom of
      action, and a positive state of emotion and an enriching life", illustrate the
      different resources and opportunities that the informants described as important
      for them to perceive themselves as healthy. The informants also reflected on
      "being ill" and "being well" and what makes the difference. Five aspects
      influenced the dynamics of their health experiences: "body and soul, prognosis,
      character of symptoms, physical and social activity, and emotional state".
      Consequently, the informants expressed a holistic view of health, where the focus
      lies on the opportunity and the ability to lead their lives the way they want.
      CONCLUSIONS: This study points at the value of taking lay perspectives on health
      into account, as it might increase the opportunity to design effective,
      personalized rehabilitation strategies. IMPLICATIONS FOR REHABILITATION:
      Musculoskeletal disorders (MSDs) are difficult to cure and actions to alleviate
      suffering are of most importance to increase wellbeing and thereby work ability.
      Research on lay perspectives can contribute towards a deepened understanding of
      the health experiences of the affected, and thereby the development of the goals
      and activities of rehabilitation. Our models, that present the view of health and
      aspects important for achieving wellness among people with MSDs, can contribute
      in the development of multimodal rehabilitation. The results can also be useful
      as a base in the evaluation of clinical practice.

PMID- 25777549
TI  - Cross-cultural adaptation, reliability and validity of the Turkish version of the
      Lower Limb Functional Index.
AB  - PURPOSE: This study aims to adapt culturally a Turkish version of the Lower Limb
      Functional Index (LLFI) and to determine its validity, reliability, internal
      consistency, measurement sensitivity and factor structure in lower limb problems.
      METHOD: The LLFI was translated into Turkish and cross-culturally adapted with a
      double forward-backward protocol that determined face and content validity.
      Individuals (n = 120) with lower limb musculoskeletal disorders completed the
      LLFI and Short Form-36 questionnaires and the Timed Up and Go physical test. The
      psychometric properties were evaluated for the all participants from patient
      reported outcome measures made at baseline and repeated at day 3 to determine
      criterion between scores (Pearson's r), internal consistency (Cronbachs alpha)
      and test-retest reliability (intraclass correlation coefficient - ICC2.1). Error
      was determined using standard error of the measurement (SEM) and minimal
      detectable change at the 90% level (MDC90), while factor structure was determined
      using exploratory factor analysis with maximum likelihood extraction and Varimax
      rotation. RESULTS: The psychometric characteristics showed strong criterion
      validity (r = 0.74-0.76), high internal consistency (alpha = 0.82) and high test
      retest reability (ICC2.1 = 0.97). The SEM of 3.2% gave an MDC90 = 5.8%. The
      factor structure was uni-dimensional. CONCLUSIONS: Turkish version of LLFI was
      found to be valid and reliable for the measurement of lower limb function in a
      Turkish population. Implications for Rehabilitation Lower extremity
      musculoskeletal disorders are common and greatly impact activities among the
      affected individuals pertaining to daily living, work, leisure and quality of
      life. Patient-reported outcome (PRO) measures have advantages as they are
      practical, cost-effective and clinically convenient for use in patient-centered
      care. The Lower Limb Functional Index is a recently validated PRO measure shown
      to have strong clinimetric properties.

PMID- 25777547
TI  - Mechanism of drug-drug interactions mediated by human cytochrome P450 CYP3A4
      monomer.
AB  - Using Nanodiscs, we quantitate the heterotropic interaction between two different
      drugs mediated by monomeric CYP3A4 incorporated into a nativelike membrane
      environment. The mechanism of this interaction is deciphered by global analysis
      of multiple-turnover experiments performed under identical conditions using the
      pure substrates progesterone (PGS) and carbamazepine (CBZ) and their mixtures.
      Activation of CBZ epoxidation and simultaneous inhibition of PGS hydroxylation
      are measured and quantitated through differences in their respective affinities
      for both a remote allosteric site and the productive catalytic site near the heme
      iron. Preferred binding of PGS at the allosteric site and a stronger preference
      for CBZ binding at the productive site give rise to a nontrivial drug-drug
      interaction. Molecular dynamics simulations indicate functionally important
      conformational changes caused by PGS binding at the allosteric site and by two
      CBZ molecules positioned inside the substrate binding pocket. Structural changes
      involving Phe-213, Phe-219, and Phe-241 are thought to be responsible for the
      observed synergetic effects and positive allosteric interactions between these
      two substrates. Such a mechanism is likely of general relevance to the mutual
      heterotropic effects caused by biologically active compounds that exhibit
      different patterns of interaction with the distinct allosteric and productive
      sites of CYP3A4, as well as other xenobiotic metabolizing cytochromes P450 that
      are also involved in drug-drug interactions. Importantly, this work demonstrates
      that a monomeric CYP3A4 can display the full spectrum of activation and
      cooperative effects that are observed in hepatic membranes. 

PMID- 25777550
TI  - Patient's experience with comorbidity management in primary care: a qualitative
      study of comorbid pain and obesity.
AB  - AIM: The aim of this research is to examine perceptions of those with comorbid
      chronic pain and obesity regarding their experience of comorbidity management in
      primary care settings. BACKGROUND: Chronic pain and obesity are common
      comorbidities frequently managed in primary care settings. Evidence suggests
      individuals with this comorbidity may be at risk for suboptimal clinical
      interactions; however, treatment experiences and preferences of those with
      comorbid chronic pain and obesity have received little attention. METHODS: Semi
      structured interviews conducted with 30 primary care patients with mean body mass
      index=36.8 and comorbid persistent pain. The constant comparative method was used
      to analyze data. FINDINGS: Participants discussed frustration with a perceived
      lack of information tailored to their needs and a desire for a personalized
      treatment experience. Participants found available medical approaches
      unsatisfying and sought a more holistic approach to management. Discussions also
      focused around the need for providers to initiate efforts at education and
      motivation enhancement and to show concern for and understanding of the unique
      difficulties associated with comorbidity. Findings suggest providers should
      engage in integrated communication regarding weight and pain, targeting this
      multimorbidity using methods aligned with priorities discussed by patients.

PMID- 25777552
TI  - Effect of initial ph on growth characteristics and fermentation properties of
      Saccharomyces cerevisiae.
AB  - As the core microorganism of wine making, Saccharomyces cerevisiae encounter low
      pH stress at the beginning of fermentation. Effect of initial pH (4.50, 3.00,
      2.75, 2.50) on growth and fermentation performance of 3 S. cerevisiae strains
      Freddo, BH8, No.7303, different tolerance at low pH, chosen from 12 strains, was
      studied. The values of yeast growth (OD600 , colony forming units, cell dry
      weight), fermentation efficiency (accumulated mass loss, change of total sugar
      concentration), and fermentation products (ethanol, glycerol, acetic acid, and l
      succinic acid) at different pH stress were measured. The results showed that the
      initial pH of must was a vital factor influencing yeast growth and alcoholic
      fermentation. Among the 3 strains, strain Freddo and BH8 were more tolerant than
      No.7303, so they were affected slighter than the latter. Among the 4 pH values,
      all the 3 strains showed adaptation even at pH 2.50; pH 2.75 and 2.50 had more
      vital effect on yeast growth and fermentation products in contrast with pH 4.50
      and 3.00. In general, low initial pH showed the properties of prolonging yeast
      lag phase, affecting accumulated mass loss, changing the consumption rate of
      total sugar, increasing final content of acetic acid and glycerol, and decreasing
      final content of ethanol and l- succinic acid, except some special cases. Based
      on this study, the effect of low pH on wine products would be better understood
      and the tolerance mechanism of low pH of S. cerevisiae could be better explored
      in future. 

PMID- 25777551
TI  - Expression signatures of long non-coding RNAs in early brain injury following
      experimental subarachnoid hemorrhage.
AB  - Subarachnoid hemorrhage (SAH) is an important cause of mortality in stroke
      patients. Long non-coding RNAs (LncRNAs) have important functions in brain
      disease, however their expression profiles in SAH remain to be elucidated. The
      present study aimed to investigate the expression signatures of LncRNAs and mRNAs
      in early brain injury (EBI) following SAH in a rat model. Male Wistar rats were
      randomly divided into an SAH group and a sham operation group. The expression
      signatures of the LncRNAs and mRNAs in the temporal lobe cortex were investigated
      using a rat LncRNAs array following experimental SAH. The results revealed that
      there were 144 downregulated and 64 upregulated LncRNAs and 181 downregulated and
      221 upregulated mRNAs following SAH. Additionally, two upregulated (BC092207,
      MRuc008hvl) and three downregulated (XR_006756, MRAK038897, MRAK017168) LncRNAs
      were confirmed using reverse transcription quantitative polymerase chain
      reaction. The differentially expressed mRNAs were further analyzed using the Gene
      Ontology and the Kyoto Encyclopedia of Genes and Genomes (KEGG) databases. The
      pathway analysis results provided by the KEGG database indicated that eight
      pathways associated with inflammation were involved in EBI following SAH. In
      conclusion, these results demonstrated that the expression profiles of the
      LncRNAs and mRNAs were significantly different between the SAH-induced EBI group
      and the sham operation group. These differently expressed LncRNAs may be
      important in EBI following SAH.

PMID- 25777553
TI  - Dynamics of T-cell subsets and their relationship with oral and systemic
      opportunistic infections in HIV/AIDS patients during the first year of HAART in
      Guangxi, China.
AB  - To analyze the dynamic changes in Th1, Th2, Tc1, and Tc2 of HIV/AIDS patients
      during the first year of highly active antiretroviral therapy (HAART) and to
      explore their relationship with oral and systemic opportunistic infections, a
      cohort study was carried out among HIV/AIDS patients in Guangxi, China. Ninety
      HIV/AIDS patients and 30 healthy controls (HC) were included. The enrolled
      HIV/AIDS patients were examined at baseline and after 3, 6, and 12 months of
      HAART. On each visit, oral and systemic opportunistic infections were recorded,
      oral Candida load and plasma viral load (VL) were counted, differential T-cell
      counts and flow cytometric analysis of T-cell subsets were performed. During the
      first year of HAART, the total number of opportunistic infections decreased
      steadily with the change in oral candidiasis (OC) most representatively. A
      significant Th1->Th2 switch (Th1/Th2 ratio 0.23 +/- 0.12, HC 1.45 +/- 0.38) and
      slight Tc1->Tc2 shift (Tc1/Tc2 ratio 0.93 +/- 0.29, HC 1.13 +/- 0.33) were found
      at baseline, and both received slow mitigation after HAART. LgCFU and clinical OC
      were correlated positively with both LgVL and clinical stage (P < 0.05) at
      baseline. LgCFU was also correlated positively with clinical stage at all four
      time points (P < 0.05). In multiple factor analysis, Th1 was confirmed to be
      correlated negatively with LgVL (Std.B = -0.295, P = 0.025) and LgCFU (Std.B = 
      0.227, P < 0.001) at baseline. After HAART, LgCFU and clinical stage were only
      correlated negatively with CD4 when all factors were included. These results
      suggest that oral candidiasis and oral Candida load could be useful clinical
      markers in the evaluation of HIV/AIDS patients. Th1 may play an important role
      against oral and systemic opportunistic infections. Tc1 and Tc2 both showed
      positive roles in the control of viremia without HAART. J. Med. Virol. 87:1158
      1167, 2015. (c) 2015 Wiley Periodicals, Inc. 

PMID- 25777554
TI  - Local recurrence following treatment for breast cancer with an endoscopic nipple
      sparing mastectomy.
AB  - PURPOSE: Endoscopic nipple-sparing mastectomy (E-NSM) has been reportedly
      associated with smaller scars and greater patient satisfaction; however, long
      term results of this procedure have not been made. The purpose of this
      retrospective study was to investigate the local recurrence (LR) rate and factors
      associated with it after E-NSM and to examine the oncologic safety of this
      procedure. METHODS: We reviewed the medical records of a total of 421 breasts in
      404 patients who underwent E-NSM to investigate the LR rate and the factors
      associated with it. The clinico-pathological features and the treatment and
      outcomes of the patients with LRs were also examined. RESULTS: Eleven breasts
      (2.6 %) in 11 patients presented with LR as the first site of recurrence after a
      median follow-up time of 61 months. Among the 11 LRs, 9 patients presented with
      LR only, 1 patient exhibited regional lymph node recurrence, and 1 patient
      exhibited distant metastasis. The median time from surgery until LR was 25
      months. Eight LRs developed near the original tumor site. The risk factors for LR
      in a multivariate analysis were a younger age of less than 40 years (p = 0.02),
      Stage III tumor (p = 0.01), and an inadequate surgical margin (p = 0.001). After
      the treatment, 6 patients had no evidence of disease, 2 patients died from
      metastatic disease, 2 patients experienced repeat LR, and the remaining patient
      who rejected excision exhibited a persistent LR. CONCLUSIONS: E-NSM is an
      oncologically safe procedure and an acceptable method in selected patients
      requiring a mastectomy.

PMID- 25777555
TI  - Recent advances in sentinel node biopsy in breast surgery.

PMID- 25777556
TI  - Estimating the costs of diabetes by episodes of care: promises and challenges.

PMID- 25777571
TI  - Integrating bone targeting radiopharmaceuticals into the management of patients
      with castrate-resistant prostate cancer with symptomatic bone metastases.
AB  - Metastatic castrate-resistant prostate cancer (CRPC) refers to the disease state
      in which metastatic prostate cancer fails to respond to androgen deprivation
      therapy (ADT). This can be manifest as a rising PSA, increase in radiographically
      measurable disease, or progression of clinical disease. Roughly 90 % of men with
      metastatic prostate cancer have bone metastases, which is a predictor of both
      morbidity and mortality. Historically, treatment has been palliative, consisting
      of external beam radiation therapy (EBRT) and pharmacological analgesics for pain
      control and osteoclast inhibitors, such as bisphosphonates and denosumab to
      mitigate skeletal-related events. Older radiopharmaceuticals, such as Strontium
      89 and Samarium-153, are Beta-emitting agents that were found to provide
      palliation but were without survival benefit and carried high risks of
      myelosuppression. Radium-223 is an Alpha-emitting radiopharmaceutical that has
      demonstrated a significant overall survival benefit in men with metastatic CRPC,
      delay to symptomatic skeletal events (SSEs), and improvement in pain control,
      with a favorable toxicity profile compared with placebo. Unlike EBRT, Radium-223
      has systemic uptake, with the potential to address several bone metastases
      concurrently and provides overall survival benefit. It is a simple administration
      with minimal complexity and shielding requirements in experienced hands. EBRT
      appears to provide a more rapid and dramatic palliative benefit to any given
      lesion. Because Radium-223 has limited myelosuppression, the two can be
      thoughtfully integrated, along with multiple agents, for the treatment of men
      with CRPC with symptomatic bone metastases. Given its excellent safety profile,
      there is interest and anecdotal safety combining Radium-223 with therapies, such
      as abiraterone and enzalutamide. Formal recommendations regarding combination
      therapies will require clinical trials. The use of Alpha-emitting
      radiopharmaceuticals in castrate-sensitive disease, in metastatic asymptomatic
      CRPC, the categorical sequencing amongst other treatments for CRPC, as well as
      the application to other primary pathologies, such as metastatic breast cancer,
      is currently evolving.

PMID- 25777573
TI  - Current treatment options for malignant peripheral nerve sheath tumors.
AB  - Malignant peripheral nerve sheath tumors (MPNST) are aggressive soft tissue
      sarcomas characterized by high risk of local recurrence and distant metastasis.
      The only known curative therapy is complete resection. Adjuvant radiation is
      recommended for larger lesions or those with more aggressive histology. Given the
      dismal prognosis in tumors that cannot be cured by surgery alone and the lack of
      systemic therapy with proven benefit, targeted therapies based on knowledge of
      activation of the Ras pathway and downstream effectors have been trialed in
      MPNST, thus far without proven benefit. However, novel or combination therapies
      based on recent preclinical advances are highly desirable and are the subject of
      ongoing clinical trials.

PMID- 25777572
TI  - Oncolytic virus immunotherapy for melanoma.
AB  - Melanoma is a type of skin cancer arising from melanocytes and is increasing in
      incidence. Although complete surgical excision of early stage lesions may be
      curative, metastatic melanoma continues to be a major therapeutic challenge.
      Advances in understanding the molecular pathways that promote tumorigenesis and
      the interactions between melanoma cells and the immune system have resulted in
      the approval of several newly targeted agents and immunotherapy strategies for
      the treatment of advanced disease. Oncolytic virus immunotherapy is a new
      approach that uses native or attenuated live viruses to selectively kill melanoma
      cells and induce systemic tumor-specific immune responses. A variety of viruses
      are now in clinical development with the attenuated oncolytic herpesvirus
      encoding granulocyte-macrophage colony stimulating factor, known as talimogene
      laherparepvec, recently demonstrating an improvement in durable response rate in
      patients with advanced melanoma compared with granulocyte-macrophage colony
      stimulating factor alone. A major advantage of talimogene laherparepvec and
      related agents is the limited toxicity and ability to use each individual tumor
      as a source of antigen to generate a highly specific antitumor immune response.
      These agents are easily administered in the out-patient setting and may be a
      reasonable option for patients with limited metastatic tumor burden, those with a
      good performance status and without extensive prior treatment, and in those who
      cannot tolerate more difficult therapeutic regimens. Further investigation into
      the impact on overall survival as monotherapy and combination of oncolytic virus
      immunotherapy with other forms of immunotherapy merit high priority for further
      clinical application of these novel agents for the treatment of melanoma and
      perhaps other cancers as well.

PMID- 25777574
TI  - A Winogradsky-based culture system shows an association between microbial
      fermentation and cystic fibrosis exacerbation.

PMID- 25777575
TI  - The host metabolite D-serine contributes to bacterial niche specificity through
      gene selection.

PMID- 25777576
TI  - Integrative mid-trimester anomaly (IMTA) chart: a novel sonographic approach for
      syndromatic challenges (pilot study).
AB  - OBJECTIVE: To validate the use of the integrative mid-trimester anomaly (IMTA)
      chart, a novel chart that aims to increase sonographers' ability to diagnose
      fetal syndromes and complex anomalies. METHODS: This study was conducted between
      September 2014 and January 2015. Pregnant women who attended our hospital for
      fetal medicine consultation during the second trimester were recruited. The
      diagnosis was assigned by a qualified consultant. The research coordinator
      randomized women between two groups (each consisted of two sonographers with
      comparable experience) and each was then examined twice (once with and once
      without the chart). Supposed diagnosis, patient and sonographer satisfactions
      were reported. RESULTS: Twenty five women were recruited. Their average age was
      26.48 +/- 4.49 years and gestational age at examination was 24.39 +/- 6.39. There
      were 17 (68%) fetuses that had multiple anomalies. The duration of examination
      was comparable. However, patient and sonographer satisfactions were higher when
      the same women were examined with the chart (p < 0.0001). The accuracy of
      diagnosis was also significantly higher (p = 0.03). CONCLUSION: The IMTA chart
      seems to be a useful tool for novice sonographers that could increase their
      diagnostic accuracy and improve their patient and their own satisfaction.

PMID- 25777577
TI  - 5-Methyl-tetrahydrofolate in prevention of recurrent preeclampsia.
AB  - OBJECTIVE: To evaluate the efficacy of 5-methyl-tetrahydrofolate (5-MTHF)
      supplementation in prevention of recurrent preeclampsia. METHODS: Retrospective
      cohort of women who received daily oral 5-MTHF 15 mg supplementation as
      prophylactic treatment since first trimester for recurrent preeclampsia were
      compared with women who did not. All asymptomatic singleton gestations with prior
      preeclampsia (in the previous pregnancy) were included. Women with chronic
      hypertension were excluded. The primary outcome was the incidence of
      preeclampsia. RESULTS: Three hundred and three singleton gestation met the
      inclusion criteria: 157 received 5-MTHF, while 146 did not (control group). Women
      who received 5-MTHF had a significantly lower incidence of recurrent overall
      preeclampsia (21.7% versus 39.7%; odds ratio (OR) 0.57, 95% confidence interval
      (CI) 0.25, 0.69), severe preeclampsia (3.2% versus 8.9%; OR 0.44, 95% CI 0.12
      0.97) and early-onset preeclampsia (1.9% versus 7.5%; OR 0.34, 95% CI 0.07-0.87)
      compared to control. The intervention group delivered about 10 d after the
      control and had higher birth weight. CONCLUSION: This retrospective study showed
      that women with prior preeclampsia who received daily oral 5-MTHF 15 mg
      supplementation had a significantly lower incidence of overall preeclampsia,
      severe preeclampsia and early-onset preeclampsia. Randomized controlled trials
      are needed to confirm our findings.

PMID- 25777578
TI  - Author's Reply: role of probiotics in prevention of Candida colonization and
      invasive candidiasis.

PMID- 25777579
TI  - Preparation of hollow CuO@SiO2 spheres and its catalytic performances for the NO
      + CO and CO oxidation.
AB  - The hollow CuO@SiO2 spheres with a mean diameter of 240 nm and a thin shell layer
      of about 30 nm in thickness was synthesized using an inorganic SiO2 shell coating
      on the surface of Cu@C composite that was prepared by a two-step hydrothermal
      method. The obtained hollow CuO@SiO2 spheres were characterized by ICP-AES,
      nitrogen adsorption-desorption, SEM, TEM, XRD, H2-TPR, CO-TPR, CO-TPD and NO-TPD.
      The results revealed that the hollow CuO@SiO2 spheres consist of CuO uniformly
      inserted into SiO2 layer. The CuO@SiO2 sample exhibits particular catalytic
      activities for CO oxidation and NO + CO reactions compared with CuO supported on
      SiO2 (CuO/SiO2). The higher catalytic activity is attributed to the special
      hollow shell structure that possesses much more highly dispersed CuO nanocluster
      that can be easy toward the CO and NO adsorption and the oxidation of CO on its
      surface.

PMID- 25777580
TI  - Increased Cortical Porosity in Older Men With Fracture.
AB  - Cortical porosity increases with age and affects bone strength, but its
      association with fracture in older men is unknown. The aim of this study was to
      investigate whether cortical porosity is associated with prevalent fractures in
      older men. A subsample of 456 men aged 80.2 +/- 3.5 (mean +/- SD) years, with
      available high-resolution peripheral quantitative computed tomography
      measurements at the tibia from the 5-year follow-up exam, was drawn from the
      prospective MrOS Gothenburg study. Dual-energy X-ray absorptiometry was used to
      measure areal bone mineral density (aBMD). Data on physical activity, calcium
      intake, medications, diseases, and smoking were collected on questionnaires at
      the follow-up exam. Of 87 men (19.1%) with fracture at or after age 50 years (all
      fracture group), 52 (11.4%) had had a self-reported fracture before the baseline
      exam and 35 (7.7%) had had an X-ray-verified fracture between baseline and follow
      up. Men in the all-fracture group and in the X-ray-verified group had 15.8%
      (13.2% +/- 4.9% versus 11.4% +/- 3.8%; p < 0.001) and 21.6% (14.1% +/- 5.2%
      versus 11.6% +/- 3.9%; p < 0.01) higher cortical porosity, respectively, than men
      in the nonfracture group. The independent associations between bone
      microstructure parameters and fracture were tested using multivariate logistic
      regression with age, height, weight, calcium intake, smoking, physical activity,
      medications, and diseases as covariates. Cortical porosity was independently
      associated with any fracture (reported or X-ray-verified; OR per SD increase
      1.49; 95% confidence interval (CI), 1.17 to 1.90) and with any X-ray-verified
      fracture alone (OR 1.73; 95% CI, 1.23 to 2.42). Including aBMD (spine or hip,
      respectively) in the multivariate logistic regression above revealed that
      cortical porosity was associated with any fracture (OR 1.54; 95% CI, 1.17 to
      2.01) and with X-ray-verified fracture alone (OR 1.49; 95% CI, 1.00 to 2.22).
      Cortical porosity was associated with prevalence of fracture even after
      adjustment for aBMD.

PMID- 25777581
TI  - An all-optical modulation method in sub-micron scale.
AB  - We report a theoretical study showing that by utilizing the illumination of an
      external laser, the Surface Plasmon Polaritons (SPP) signals on the graphene
      sheet can be modulated in the sub-micron scale. The SPP wave can propagate along
      the graphene in the middle infrared range when the graphene is properly doped.
      Graphene's carrier density can be modified by a visible laser when the graphene
      sheet is exfoliated on the hydrophilic SiO2/Si substrate, which yields an all
      optical way to control the graphene's doping level. Consequently, the external
      laser beam can control the propagation of the graphene SPP between the ON and OFF
      status. This all-optical modulation effect is still obvious when the spot size of
      the external laser is reduced to 400 nm while the modulation depth is as high as
      114.7 dB/MUm.

PMID- 25777582
TI  - Cannabinoid replacement therapy (CRT): Nabiximols (Sativex) as a novel treatment
      for cannabis withdrawal.
AB  - Cannabis is a common recreational drug that is generally considered to have low
      addictive potential. However, an increasing number of cannabis users are seeking
      treatment for dependence on the drug. There is interest in using agonist
      (substitution) pharmacotherapies to treat cannabis dependence and here we outline
      a novel approach involving a buccal spray (nabiximols) that contains
      tetrahydrocannabinol (THC) and cannabidiol (CBD). We review recent research with
      nabiximols and highlight findings relevant to clinical practice. 

PMID- 25777583
TI  - Synthesis and evaluation of a (3R,6S,9S)-2-oxo-1-azabicyclo[4.3.0]nonane scaffold
      as a mimic of Xaa-trans-Pro in poly-L-proline type II helix conformation.
AB  - We describe the development of a small-molecule mimic of Xaa-trans-Pro dipeptide
      in poly-l-proline type II helix conformation, based upon a (3R,6S,9S)-2-oxo-1
      azabicyclo[4.3.0]nonane core structure. Stereoselective synthesis of the mimic
      from l-pyroglutamic acid is achieved in twelve linear steps and 9.9% yield.
      Configurational and conformational analyses are conducted using a combination of
      (1)H NMR spectroscopy, X-ray crystallography and circular dichroism spectroscopy;
      and evaluation of the mimic as a promising surrogate dipeptide, in a protein
      protein interaction between the SH3 domain of human Fyn kinase (Fyn SH3) and
      peptidomimetics of its biological ligand, are conducted by (1)H-(15)N HSQC NMR
      titration experiments. 

PMID- 25777584
TI  - Twist versus linkage mode: which one is better for the construction of blue
      luminogens with AIE properties?
AB  - Two new blue luminogens, Py-4MethylTPE and Py-4mTPE, constructed with a pyrene
      core and tetraphenylethene peripheries, have been successfully obtained. These
      two luminogens show AIE and AEE effects, respectively, as a result of minor
      differences in their structures. An OLED device based on Py-4mTPE exhibits a good
      performance (etaC,max = 4.02 cd A(-1), lambdaEL,max = 436 nm) and reveals the
      powerful effect of a different linkage mode for the construction of blue AIE
      luminogens.

PMID- 25777585
TI  - Demographic and socio-economic differences between men seeking infertility
      evaluation and those seeking surgical sterilization: from the National Survey of
      Family Growth.
AB  - OBJECTIVE: To identify differences in demographic and socio-economic factors
      between men seeking infertility evaluation and those undergoing vasectomy, to
      address disparities in access to these services. PATIENTS AND METHODS: Data from
      Cycle 6 and Cycle 7 (2002 and 2006-2008) of the National Survey of Family Growth
      (NSFG) were reviewed. The NSFG is a multistage probability survey designed to
      capture a nationally representative sample of households with men and women aged
      15-45 years in the USA. The variables analysed included age, body mass index,
      self-reported health, alcohol use, race, religious affiliation, marital status,
      number of offspring, educational attainment, income level, insurance status and
      metropolitan home designation. Our primary outcome was the correlation of these
      demographic and socio-economic factors with evaluation for male infertility or
      vasectomy. RESULTS: Of the 11 067 men identified through the NSFG, 466 men (4.2%)
      sought infertility evaluation, representing 2 187 455 men nationally, and 326
      (2.9%) underwent a vasectomy, representing 1 510 386 men nationally. Those
      seeking infertility evaluation were more likely to be younger and have fewer
      children (P = 0.001, 0.001) and less likely to be currently married (78 vs 74%; P
      = 0.010) or ever married (89 vs 97%; P = 0.002). Men undergoing a vasectomy were
      more likely to be white (86 vs 70%; P = 0.001). Men seeking infertility
      evaluation were more likely to have a college or graduate degree compared with
      men undergoing a vasectomy (68 vs 64%; P = 0.015). There was no difference
      between the two groups for all other variables. CONCLUSION: While differences in
      demographic characteristics such as age, offspring number and marital status were
      identified, measures of health, socio-economic status, religion and insurance
      were similar between men undergoing vasectomy and those seeking infertility
      services. These factors help characterize the utilization of male reproductive
      health services in the USA and may help address disparities in access to these
      services and improve public health strategies.

PMID- 25777586
TI  - Long-term follow-up after first-line bronchoscopic therapy in patients with
      bronchial carcinoids.
AB  - BACKGROUND: Carcinoid of the lung is considered to be a low-grade malignancy. A
      subgroup presents as an endobronchial tumour. Surgical resection is considered
      the standard approach because of its metastatic potential and the possibility of
      an iceberg phenomenon for the endobronchial subgroup. Advances in non-invasive
      and minimally invasive technologies seem to justify a more lung parenchyma
      sparing approach. METHODS: In patients presenting with bronchial carcinoids,
      initial bronchoscopic treatment (IBT) is first attempted for complete tumour
      eradication and sufficient tissue sampling for the proper differentiation of
      typical (TC) versus atypical (AC) histological type. Furthermore in cases with
      postobstruction problems the desobstruction is aimed at improving the patient's
      condition and by that alleviate surgery if that is needed. High resolution CT is
      performed 6 weeks post IBT to determine local tumour growth. Surgical resection
      follows in case of extraluminal disease, residual carcinoid inaccessible for IBT,
      or late recurrences not salvaged by repeat IBT. RESULTS: Minimum follow-up was 5
      years from start of treatment for 112 patients (65 women, 47 men), with a median
      age of 47 years (range 16-77 years). Eighty-three patients (74%) had TC, and 29
      (26%) AC. IBT only was ultimately curative in 42% of the cases (47/112): 42 TC, 5
      AC. Disease-specific mortality including surgical mortality has been 2.6% (3/112)
      in patients with extraluminal carcinoids (3 AC). CONCLUSIONS: IBT, if with
      unsuccessful rescue surgery, is justifiable with excellent long-term outcome. IBT
      made surgery unnecessary in 42% of the cases. Iceberg phenomenon and metastatic
      potential in this group of patients with bronchial carcinoids are clinically
      insignificant.

PMID- 25777587
TI  - Discovery of novel plasma protein biomarkers to predict imminent cystic fibrosis
      pulmonary exacerbations using multiple reaction monitoring mass spectrometry.
AB  - BACKGROUND: Despite the significant morbidity and mortality related to pulmonary
      exacerbations in cystic fibrosis (CF), there remains no reliable predictor of
      imminent exacerbation. OBJECTIVE: To identify blood-based biomarkers to predict
      imminent (<4 months from stable blood draw) CF pulmonary exacerbations using
      targeted proteomics. METHODS: 104 subjects provided plasma samples when
      clinically stable and were randomly split into discovery (n=70) and replication
      (n=34) cohorts. Multiple reaction monitoring mass spectrometry (MRM-MS) was used
      to measure 117 peptides (79 proteins) from plasma. Plasma proteins with
      differential abundance between subjects who did versus did not develop an
      imminent exacerbation were analysed and proteins with fold difference >1.5
      between the groups were included in an MRM-MS classifier model to predict
      imminent exacerbations. Performance characteristics were compared with clinical
      predictors and candidate plasma protein biomarkers. RESULTS: Six proteins were
      included in the final MRM-MS protein panel. The area under the curve (AUC) for
      the prediction of imminent exacerbations was highest for the MRM-MS protein panel
      (AUC 0.74) in comparison to FEV1% predicted (AUC 0.55) and the top candidate
      plasma protein biomarkers, including C-reactive protein (AUC 0.61) and
      interleukin-6 (AUC 0.60). The MRM-MS protein panel performed similarly in the
      replication cohort (AUC 0.73). CONCLUSIONS: Using MRM-MS, a six-protein panel
      measured from plasma can distinguish individuals with versus without an imminent
      exacerbation. With further replication and assay development, this biomarker
      panel may be clinically applicable for prediction of exacerbations in individuals
      with CF.

PMID- 25777588
TI  - Impact of a male-only weight loss maintenance programme on social-cognitive
      determinants of physical activity and healthy eating: A randomized controlled
      trial.
AB  - OBJECTIVES: To examine the effect of a gender-tailored, Social Cognitive Theory
      (SCT)-based weight loss maintenance (WLM) intervention on men's physical activity
      and healthy eating cognitions and behaviours in the 12 months after completing a
      weight loss programme. DESIGN: A two-phase, assessor-blinded, randomized
      controlled trial. METHODS: Ninety-two overweight/obese men (mean [SD] age: 49.2
      years [10.1], BMI: 30.7 [3.3] kg/m(2) ) who lost at least 4 kg after completing
      the 3-month SCT-based SHED-IT Weight Loss Program were randomly allocated to
      receive (1) the SCT-based SHED-IT WLM Program; or (2) no additional resources
      (self-help control group). The 6-month gender-tailored SHED-IT WLM Program was
      completely self-administered and operationalized SCT behaviour change principles
      to assist men to increase moderate-to-vigorous physical activity (MVPA) and
      decrease energy-dense, nutrient-poor (discretionary) food consumption after
      initial weight loss. After randomization (WLM baseline), men were reassessed at 6
      months (WLM post-test) and 12 months (6-month WLM follow-up). SCT cognitions
      (e.g., self-efficacy, goal setting), MVPA, and discretionary food consumption
      were assessed with validated measures. RESULTS: Following significant
      improvements in cognitions, MVPA and discretionary food consumption during the
      weight loss phase, intention-to-treat, linear mixed models revealed no
      significant group-by-time differences in cognitions or behaviours during the WLM
      phase. Initial improvements in MVPA and some cognitions (e.g., goal setting,
      planning, and social support) were largely maintained by both groups at the end
      of the study. Dietary effects were not as strongly maintained, with the
      intervention and control groups maintaining 57% and 75% of the Phase I
      improvements in discretionary food intake, respectively. CONCLUSIONS: An
      additional SCT-based WLM programme did not elicit further improvements over a
      self-help control in the cognitions or behaviours for MVPA or discretionary food
      intake of men who had lost weight with a SCT-based weight loss programme.
      Statement of contribution What is already known on this subject?Weight regain
      after weight loss (WL) is common. As successful weight loss maintenance (WLM)
      requires sustained improvements in cognitions and behaviours, health psychology
      can contribute to intervention development. However, little research has examined
      the utility of psychological theory in the context of a WLM randomised controlled
      trial. What does this study add? A theory-based WL program improved men's
      physical activity and dietary behaviours and cognitions. Men who also received a
      theory-based WLM program did not show further improvements in physical activity
      or dietary cognitions and behaviours compared to those that did not.

PMID- 25777589
TI  - Misinterpretation of the American College of Radiology white paper on managing
      incidental thyroid nodules.

PMID- 25777590
TI  - Total tumor volume and alpha-fetoprotein for selection of transplant candidates
      with hepatocellular carcinoma: A prospective validation.
AB  - The selection of liver transplantation (LT) candidates with hepatocellular
      carcinoma (HCC) is currently validated based on Milan criteria. The use of
      extended criteria has remained a matter of debate, mainly because of the absence
      of prospective validation. The present prospective study recruited patients
      according to the previously proposed total tumor volume (TTV; <=115 cm(3) )/alpha
      fetoprotein (AFP; <=400 ng/mL) score. Patients with AFP >400 ng/mL were excluded,
      and, as such, the Milan group was modified to include only patients with AFP <400
      ng/mL; these patients were compared to patients beyond Milan, but within TTV/AFP.
      From January 2007 to March 2013, 233 patients with HCC were listed for LT. Of
      them, 195 patients were within Milan and 38 beyond Milan, but within TTV/AFP. The
      average follow-up from listing was 33.9 +/- 24.9 months. Risk of dropout was
      higher for patients beyond Milan, but within TTV/AFP (16 of 38; 42.1%), than for
      those within Milan (49 of 195 [25.1%]; P = 0.033). In parallel, intent-to-treat
      survival from listing was lower in patients beyond Milan (53.8% vs. 71.6% at 4
      years; P < 0.001). After a median waiting time of 8 months, 166 patients were
      transplanted, 134 within Milan criteria, and 32 beyond Milan but within TTV/AFP.
      They demonstrated acceptable and similar recurrence rates (4.5% vs. 9.4%; P =
      0.138) and post-transplant survivals (78.7% vs. 74.6% at 4 years; P = 0.932).
      CONCLUSION: Based on the present prospective study, HCC LT candidate selection
      could be expanded to the TTV (<=115 cm(3) )/AFP (<=400 ng/mL) criteria in centers
      with at least 8-month waiting time. An increased risk of dropout on the waiting
      list can be expected, but with equivalent and satisfactory post-transplant
      survival.

PMID- 25777609
TI  - Childhood Physical Performance Measures and Adulthood Knee Cartilage Volume and
      Bone Area: A 25-Year Cohort Study.
AB  - OBJECTIVE: We aimed to determine the associations between childhood physical
      performance measures and tibial cartilage volume and tibial bone area in adults
      25 years later. METHODS: Participants (n = 330, ages 31-41 years, female 47%)
      were selected from the Australian Schools Health and Fitness Survey of 1985. The
      participants underwent T1-weighted fat-suppressed magnetic resonance imaging
      (MRI) of their knees. Tibial bone area and cartilage volume were measured from
      MRI. Childhood measures, including physical work capacity at 170 beats per minute
      (PWC170 ), leg strength, number of sit-ups, long-run, and short-run were measured
      in 1985. PWC170 and leg strength measures were repeated after 20 years in their
      adulthood. Linear regression analysis was used to determine the association of
      performance measures with cartilage volume. RESULTS: There were consistent
      positive associations of all childhood measures, including PWC170 (beta = 0.38
      cm(2) per 10 watts, 95% confidence interval [95% CI] 0.15, 0.60), leg strength,
      long-run, short-run, and sit-ups with adult medial and total tibial bone area.
      Similarly, there was an association of PWC170 and sit-ups with adult medial
      tibial cartilage volume. After further adjustment for tibial bone area, the
      association between PWC170 and medial and total (beta = 0.08 cm(3) per 10 watts,
      95% CI 0.02, 0.10) tibial cartilage volume decreased in magnitude but remained
      significant. CONCLUSION: Childhood physical performance measures, especially
      PWC170 , were associated with knee tibial bone area and cartilage volume in
      adulthood. The associations with cartilage volume appeared to be partially
      mediated by bone area. This suggests physical performance measures in childhood
      can independently influence adult knee structures.

PMID- 25777610
TI  - Cell-penetrating antimicrobial peptides - prospectives for targeting
      intracellular infections.
AB  - PURPOSE: To investigate the suitability of three antimicrobial peptides (AMPs) as
      cell-penetrating antimicrobial peptides. METHODS: Cellular uptake of three AMPs
      (PK-12-KKP, SA-3 and TPk) and a cell-penetrating peptide (penetratin), all 5(6)
      carboxytetramethylrhodamine-labeled, were tested in HeLa WT cells and analyzed by
      flow cytometry and confocal microscopy. Furthermore, the effects of the peptides
      on eukaryotic cell viability as well as their antimicrobial effect were tested.
      In addition, the disrupting ability of the peptides in the presence of bilayer
      membranes of different composition were analyzed. RESULTS: AMP uptake relative to
      penetratin was ~13% (PK-12-KKP), ~66% (SA-3) and ~50% (TPk). All four peptides
      displayed a punctate uptake pattern in HeLa WT cells with co-localization to
      lysosomes and no indication that clathrin-mediated endocytosis was the
      predominant uptake mechanism. TPk showed the highest antibacterial activity. SA-3
      exhibited selective disruption of liposomes mimicking Gram-positive and Gram
      negative membranes. CONCLUSION: PK-12-KKP is an unlikely candidate for targeting
      intracellular bacteria, as the eukaryotic cell-penetrating ability is poor. SA-3,
      affected the cellular viability to an unacceptable degree. TPk showed acceptable
      uptake efficiency, high antimicrobial activity and relatively low toxicity, and
      it is the best potential lead peptide for further development.

PMID- 25777611
TI  - Synthesis and Evaluation of Substituted Poly(organophosphazenes) as a Novel
      Nanocarrier System for Combined Antimalarial Therapy of Primaquine and
      Dihydroartemisinin.
AB  - PURPOSE: The synthesis and evaluation of novel biodegradable
      poly(organophosphazenes) (3-6) namely poly[bis-(2-propoxy)]phosphazene (3)
      poly[bis(4-acetamidophenoxy)]phosphazene (4)poly[bis(4-formylphenoxy)]phosphazene
      (5) poly[bis(4-ethoxycarbonylanilino)]phosphazene (6) bearing various hydrophilic
      and hydrophobic side groups for their application as nonocarrier system for
      antimalarial drug delivery is described. METHODS: The characterization of
      polymers was carried out by IR, (1)H-NMR and (31)P-NMR. The molecular weights of
      these novel polyphosphazenes were determined using size exclusion chromatography
      with a Waters 515 HPLC Pump and a Waters 2414 refractive index detector. The
      degradation behavior was studied by 200 mg pellets of polymers in phosphate
      buffers pH 5.5, 6.8 and 7.4 at 37 degrees C. The degradation process was
      monitored by changes of mass as function of time and surface morphology of
      polymer pellets. The developed combined drugs nanoparticles formulations were
      evaluated for antimalarial potential in P. berghei infected mice. RESULTS: These
      polymers exhibited hydrolytic degradability, which can afford applications to a
      variety of drug delivery systems. On the basis of these results, the synthesized
      polymers were employed as nanocarriers for targeted drug delivery of primaquine
      and dihydroartemisinin. The promising in vitro release of both the drugs from
      nanoparticles formulations provided an alternative therapeutic combination
      therapy regimen for the treatment of drug resistant malaria. The nanoparticles
      formulations tested in resistant strain of P. berghei infected mice showed 100%
      antimalarial activity. CONCLUSIONS: The developed nanocarrier system provides an
      alternative combination regimen for the treatment of resistant malaria.

PMID- 25777612
TI  - The Development of Direct Extrusion-Injection Moulded Zein Matrices as Novel Oral
      Controlled Drug Delivery Systems.
AB  - PURPOSE: To evaluate the potential of zein as a sole excipient for controlled
      release formulations prepared by hot melt extrusion. METHODS: Physical mixtures
      of zein, water and crystalline paracetamol were hot melt extruded (HME) at 80
      degrees C and injection moulded (IM) into caplet forms. HME-IM Caplets were
      characterised using differential scanning calorimetry, ATR-FTIR spectroscopy,
      scanning electron microscopy and powder X-ray diffraction. Hydration and drug
      release kinetics of the caplets were investigated and fitted to a diffusion
      model. RESULTS: For the formulations with lower drug loadings, the drug was found
      to be in the non-crystalline state, while for the ones with higher drug loadings
      paracetamol is mostly crystalline. Release was found to be largely independent of
      drug loading but strongly dependent upon device dimensions, and predominately
      governed by a Fickian diffusion mechanism, while the hydration kinetics shows the
      features of Case II diffusion. CONCLUSIONS: In this study a prototype controlled
      release caplet formulation using zein as the sole excipient was successfully
      prepared using direct HME-IM processing. The results demonstrated the unique
      advantage of the hot melt extruded zein formulations on the tuneability of drug
      release rate by alternating the device dimensions.

PMID- 25777614
TI  - Severe Pulmonary Vein Stenosis and Extensive Left Atrial Stricture After
      Radiofrequency Catheter Ablation of Atrial Fibrillation.

PMID- 25777613
TI  - Novel Self-assembled, Gel-core Hyaluosomes for Non-invasive Management of
      Osteoarthritis: In-vitro Optimization, Ex-vivo and In-vivo Permeation.
AB  - PURPOSE: Hyaluronic acid (HA) is an imperative biomaterial with desirable
      rheological properties to alleviate symptoms of osteoarthritis. Nevertheless,
      scantly percutaeous permeation of this macromolecule handicaps its effective use
      for orthopedics and triggers intra-articular injection as the only surrogate.
      This study presents novel self-assembeld HA-based gel core elastic nanovesicles,
      (hyaluosomes; GC-HS), for non-invasive transdermal delivery of HA. METHODS: GC-HS
      were prepared with 1% HA using simple film hydration technique. Their size, zeta
      potential, percentage entrapment efficiency (% EE), elasticity, and ex-vivo
      transdermal permeation were evaluated compared to conventional liposomes CL.
      Structure elucidation of the formed novel system was performed using light,
      polarizing and transmission electron microscopy. In-vivo permeation of GC-HS
      through knee joints of female Sprague Dawley rats was compared to CL and HA
      alone. RESULTS: GC-HS showed nanosize (232.8 +/- 7.2), high negative zeta
      potential (-45.1 +/- 8.3) and higher elasticity (size alteration 5.43%) compared
      to CL. This novel system has self-penetration enhancing properties compared to CL
      and plain gel. GC-HS showed self-assembled properties and high physically stable
      for at least 6 months at 4 degrees C. Ex-vivo permeation of HS was significantly
      higher than CL and plain HA gel alone. In-vivo study exhibited significant six
      folds increase in transdermal permeation of HA to knee joints from GC-HS compared
      to plain HA gel. CONCLUSION: Novel GC-HS are promising nanogels for topical
      management of osteoarthritis surrogating the need for intra-articular injection.

PMID- 25777615
TI  - Associations between maternal factors during pregnancy and risk of acute
      lymphoblastic leukemia: Plausibility rules.

PMID- 25777616
TI  - Chromosomal damage and EROD induction in tree swallows (Tachycineta bicolor)
      along the Upper Mississippi River, Minnesota, USA.
AB  - The health of tree swallows, Tachycineta bicolor, on the Upper Mississippi River
      (UMR) was assessed in 2010 and 2011 using biomarkers at six sites downriver of
      Minneapolis/St. Paul, MN metropolitan area, a tributary into the UMR, and a
      nearby lake. Chromosomal damage was evaluated in nestling blood by measuring the
      coefficient of variation of DNA content (DNA CV) using flow cytometry. Cytochrome
      P450 1A activity in nestling liver was measured using the ethoxyresorufin-O
      dealkylase (EROD) assay, and oxidative stress was estimated in nestling livers
      via determination of thiobarbituric acid reacting substances (TBARS), reduced
      glutathione (GSH), oxidized glutathione (GSSG), the ratio GSSG/GSH, total
      sulfhydryl, and protein bound sulfhydryl (PBSH). A multilevel regression model
      (DNA CV) and simple regressions (EROD and oxidative stress) were used to evaluate
      biomarker responses for each location. Chromosomal damage was significantly
      elevated at two sites on the UMR (Pigs Eye and Pool 2) relative to the Green
      Mountain Lake reference site, while the induction of EROD activity was only
      observed at Pigs Eye. No measures of oxidative stress differed among sites.
      Multivariate analysis confirmed an increased DNA CV at Pigs Eye and Pool 2, and
      elevated EROD activity at Pigs Eye. These results suggest that the health of tree
      swallows has been altered at the DNA level at Pigs Eye and Pool 2 sites, and at
      the physiological level at Pigs Eye site only. 

PMID- 25777617
TI  - Levels of functional disability in elderly people in Tanzania with dementia,
      stroke and Parkinson's disease.
AB  - BACKGROUND: Disability is associated with increasing age and poverty, yet there
      are few reliable data regarding disability amongst the elderly in low-income
      countries. The aim of this study was to compare disability levels for three of
      the most common neurological, non-communicable diseases: dementia, stroke and
      Parkinson's disease (PD). METHODS: We performed a community-based study of people
      aged 70 years and over in 12 randomly selected villages in the rural Hai district
      of Tanzania. Participants underwent disability assessment using the Barthel
      Index, and clinical assessment for dementia, stroke and PD. RESULTS: In a
      representative cohort of 2232 people aged 70 years and over, there were 54 cases
      of stroke, 12 cases of PD and estimated (by extrapolation from a sub-sample of
      1198 people) to be 112 cases of dementia. People with stroke were the most
      disabled, with 62.9% having moderate or severe disability. Levels of moderate or
      severe disability were 41.2% in people with dementia and 50.0% in people with PD.
      However, the higher prevalence of dementia meant that, at a population level, it
      was associated with similar levels of disability as stroke, with 18.5% of 249
      people identified as having moderate or severe disability having dementia,
      compared to 13.7% for stroke and 2.4% for PD. CONCLUSIONS: Levels of disability
      from these conditions is high and is likely to increase with demographic ageing.
      Innovative, community-based strategies to reduce disability levels should be
      investigated.

PMID- 25777618
TI  - The Tumor Suppressor NKX3.1 Is Targeted for Degradation by DYRK1B Kinase.
AB  - NKX3.1 is a prostate-specific homeodomain protein and tumor suppressor whose
      expression is reduced in the earliest phases of prostatic neoplasia. NKX3.1
      expression is not only diminished by genetic loss and methylation, but the
      protein itself is a target for accelerated degradation caused by inflammation
      that is common in the aging prostate gland. NKX3.1 degradation is activated by
      phosphorylation at C-terminal serine residues that mediate ubiquitination and
      protein turnover. Because NKX3.1 is haploinsufficient, strategies to increase its
      protein stability could lead to new therapies. Here, a high-throughput screen was
      developed using an siRNA library for kinases that mediate NKX3.1 degradation.
      This approach identified several candidates, of which DYRK1B, a kinase that is
      subject to gene amplification and overexpression in other cancers, had the
      greatest impact on NKX3.1 half-life. Mechanistically, NKX3.1 and DYRK1B were
      shown to interact via the DYRK1B kinase domain. In addition, an in vitro kinase
      assay showed that DYRK1B phosphorylated NKX3.1 at serine 185, a residue critical
      for NKX3.1 steady-state turnover. Lastly, small-molecule inhibitors of DYRK1B
      prolonged NKX3.1 half-life. Thus, DYRK1B is a target for enzymatic inhibition in
      order to increase cellular NKX3.1. IMPLICATIONS: DYRK1B is a promising and novel
      kinase target for prostate cancer treatment mediated by enhancing NKX3.1 levels.

PMID- 25777619
TI  - [Total laparoscopic hysterectomy and same-day discharge: Satisfaction evaluation
      and feasibility study].
AB  - OBJECTIVE: To evaluate the safety and patients' satisfaction after outpatient
      laparoscopic hysterectomy (LH). METHODS: A retrospective case series of 47
      patients discharged home the same day after total LH. Outcomes include the same
      day discharge rate, complication and readmission rates, patients' short-term
      satisfaction and an evaluation of patients' opinion several months later.
      RESULTS: Among the 47 patients, 42 (89%) were discharged the same day. Five
      patients remained hospitalized due to postoperative complications (4 patients)
      and the patient's decision (1 patient). No patient required emergency
      consultation, readmission or reoperation in the first 72hours after discharge.
      Six patients (13%) had postoperative complications within the first 3 months
      after the surgery. Four patients (8%) were readmitted, three of them (6%) had to
      undergo a second surgery. In the short-term assessment, patients were satisfied
      with the management in 93% of cases and would recommend it to others, with a
      median satisfaction rate of 3.8 out of 4. CONCLUSION: Ambulatory laparoscopic
      hysterectomy is feasible in a well-selected population, with a high level of
      patients' satisfaction. This management could be an alternative to traditional
      long hospital stays proposed in France.

PMID- 25777620
TI  - Enzymatic hydrolysis of anchovy fine powder at high and ambient pressure, and
      characterization of the hydrolyzates.
AB  - BACKGROUND: At specific conditions of high pressure, the stability and activity
      of some enzymes are reportedly known to increase. The aim of this study was to
      apply pressure-tolerant proteases to hydrolyzing anchovy fine powder (AFP) and to
      determine product characteristics of the resultant hydrolyzates. RESULTS: Anchovy
      fine powder enzyme hydrolyzates (AFPEHs) were produced at 300 MPa and ambient
      pressure using combinations of Flavourzyme 500MG, Alcalase 2.4L, Marugoto E and
      Protamex. When the same protease combination was used for hydrolysis, the
      contents of total soluble solids, total water-soluble nitrogen and
      trichloroacetic acid-soluble nitrogen in the AFPEHs produced at 300 MPa were
      conspicuously higher than those in the AFPEHs produced at ambient pressure. This
      result and electrophoretic characteristics indicated that the high-pressure
      process of this study accelerates protein hydrolysis compared with the ambient
      pressure counterpart. Most peptides in the hydrolyzates obtained at 300 MPa had
      molecular masses less than 5 kDa. Functionality, sensory characteristics and the
      content of total free amino acids of selected hydrolyzates were also determined.
      CONCLUSION: The high-pressure hydrolytic process utilizing pressure-tolerant
      proteases was found to be an efficient method for producing protein hydrolyzates
      with good product characteristics.

PMID- 25777621
TI  - Cognitive behavioural interventions for depression in chronic neurological
      conditions: a systematic review.
AB  - OBJECTIVE: Chronic neurological conditions (CNCs) affect over one million people
      in the UK alone. Individuals with CNCs endure an increased prevalence of comorbid
      depression and anxiety. Poor mental health exacerbates the cost of the treatment
      and management of CNCs. CBT is recommended for the treatment of depression.
      However the application of CBT to individuals with CNCs may be limited by disease
      characteristics (e.g. mobility issues restricting therapy attendance and reducing
      engagement with behavioural activation, as well as difficulties challenging the
      veracity of disease-related negative thoughts that may reflect accurate
      appraisals). The objective of this review is to assess the clinical effectiveness
      of cognitive and behavioural interventions for depressive symptoms in individuals
      with non-acquired, medically explained CNCs. DATA SOURCES: Searches of The
      Cochrane Controlled Trials Register, PubMed, and PsychINFO were conducted.
      RESULTS: All studies suggested that CBT is an effective treatment for depression
      comorbid to CNCs, however when CBT was compared to an active therapy control
      condition, between group differences were unstable. CONCLUSION: CBT has promise
      for the treatment for depression in such conditions; however treatment protocols
      and outcome measures should be adapted for this population. Future trials should
      control for non-specific effects of therapy and, as much as possible, introduce
      blinding into methodologies.

PMID- 25777622
TI  - Improving the Specificity of the Prostate-Specific Antigen Substrate Glutaryl-Hyp
      Ala-Ser-Chg-Gln as a Promoiety.
AB  - To develop PSA peptide substrates with improved specificity and plasma stability
      from the known substrate sequence glutaryl-Hyp-Ala-Ser-Chg-Gln, systematic
      replacements of the N-terminal segment with D-retro-inverso-peptides were
      performed with the incorporation of 7-amino-4-methylcoumarin (7-AMC) after Gln
      for convenient fluorometric determination and ranking of the PSA substrate
      activity. The D-retro-inverso-peptide conjugates with P2-P5 D-amino acid
      substitutions were moderate but poorer PSA substrates as compared to the original
      peptide, suggesting that inversion of the amide bonds and/or incorporation of the
      additional atom as in the urea linker adversely affected PSA binding. However, P5
      substitution of Hyp with Ser showed significant improvements in PSA cleavage
      rate; the resulting AMC conjugate, glutaryl-Ser-Ala-Ser-Chg-Gln-AMC (11),
      exhibited the fastest PSA cleavage rate of 351 pmol/min/100 nmol PSA. In
      addition, GABA<-mGly-Ala-Ser-Chg-Gln-AMC (conjugate 6) was the second best PSA
      substrate and released 7-AMC at a rate of 225 pmol/min/100 nmol PSA as compared
      to 171 pmol/min/100 nmol PSA for the control conjugate glutaryl-Hyp-Ala-Ser-Chg
      Gln-AMC. Incubations of selected AMC conjugates with mouse and human plasma
      revealed that GABA<-D-Ser-psi[NH-CO-NH]-Ala-Ser-Chg-Gln-AMC (5) and GABA<-mGly
      Ala-Ser-Chg-Gln-AMC (6) were most stable to non-PSA-mediated proteolysis. Our
      results suggest that the PSA specificity of glutaryl-Hyp-Ala-Ser-Chg-Gln is
      improved with Ser and mGly substitutions of Hyp at the P5. 

PMID- 25777625
TI  - HLA typing using next generation sequencing: An overview.

PMID- 25777626
TI  - RTOG, CTCAE and WHO criteria for acute radiation dermatitis correlate with
      cutaneous blood flow measurements.
AB  - BACKGROUND: Various clinician-assessed scoring criteria have been used to grade
      acute radiation dermatitis. However, it is not known whether these scoring
      criteria correlate with changes in objective skin biophysical parameters and
      patient-reported symptoms following radiotherapy. We seek to correlate three
      different clinician-assessed scoring criteria with skin biophysical changes and
      patient-reported symptoms in breast cancer patients undergoing radiotherapy.
      METHODS: A prospective cohort study was performed in a university hospital
      medical center. The severity of acute radiation dermatitis in 101 breast cancer
      patients was graded using the RTOG, CTCAE and WHO clinical scoring criteria. We
      also measured various skin biophysical parameters (skin blood flow, pigmentation,
      hydration, and pH) by non-invasive techniques before and after radiotherapy.
      Patient-reported breast symptoms (pain, itching, local heat, and tightness) were
      evaluated using a questionnaire. RESULTS: The three different clinician-assessed
      scoring criteria correlated most strongly with changes in cutaneous blood flow
      following radiotherapy for breast cancer (correlation coefficient 0.70 for RTOG,
      0.68 for CTCAE, and 0.50 for WHO). All three scoring criteria also showed
      moderate correlation with changes in skin pigmentation (correlation coefficients
      0.4-0.5), but showed no significant correlation with skin hydration or pH
      (correlation coefficients <0.2). The scoring criteria correlated poorly with
      patient-reported breast symptoms (correlation coefficients <0.3). CONCLUSIONS:
      The three clinician-assessed scoring criteria (especially the RTOG and CTCAE
      criteria) show strong correlation with cutaneous blood flow measurements, but
      correlate less well with other skin biophysical parameters and patient-reported
      symptoms.

PMID- 25777627
TI  - Birth weight and maternal socioeconomic circumstances were inversely related to
      systolic blood pressure among Afro-Caribbean young adults.
AB  - OBJECTIVES: In this study, we examined the effects of birth weight (BWT) and
      early life socioeconomic circumstances (SEC) on systolic blood pressure (SBP) and
      diastolic blood pressure (DBP) among Jamaican young adults. STUDY DESIGN AND
      SETTING: Longitudinal study of 364 men and 430 women from the Jamaica 1986 Birth
      Cohort Study. Information on BWT and maternal SEC at child's birth was linked to
      information collected at 18-20 years old. Sex-specific multilevel linear
      regression models were used to examine whether adult SBP/DBP was associated with
      BWT and maternal SEC. RESULTS: In unadjusted models, SBP was inversely related to
      BWT z-score in both men (beta, -0.82 mm Hg) and women (beta, -1.18 mm Hg) but
      achieved statistical significance for women only. In the fully adjusted model,
      one standard deviation increase in BWT was associated with 1.16 mm Hg reduction
      in SBP among men [95% confidence interval (CI): 2.15, 0.17; P = 0.021] and 1.34
      mm Hg reduction in SBP among women (95% CI: 2.21, 0.47; P = 0.003). Participants
      whose mothers had lower SEC had higher SBP compared with those with mothers of
      high SEC (beta, 3.4-4.8 mm Hg for men, P < 0.05 for all SEC categories and 1.8
      2.1 for women, P > 0.05). CONCLUSION: SBP was inversely related to maternal SEC
      and BWT among Jamaican young adults.

PMID- 25777628
TI  - Task Force 3: Pediatric Cardiology Fellowship Training in Cardiac
      Catheterization.

PMID- 25777629
TI  - COCATS 4 Task Force 5: Training in Echocardiography.

PMID- 25777630
TI  - Task Force 1: Pediatric Cardiology Fellowship Training in General Cardiology.

PMID- 25777631
TI  - Task Force 2: Pediatric Cardiology Fellowship Training in Noninvasive Cardiac
      Imaging.

PMID- 25777632
TI  - Task Force 6: Pediatric Cardiology Fellowship Training in Adult Congenital Heart
      Disease.

PMID- 25777633
TI  - Task Force 4: Pediatric Cardiology Fellowship Training in Electrophysiology.

PMID- 25777634
TI  - 2015 SPCTPD/ACC/AAP/AHA Training Guidelines for Pediatric Cardiology Fellowship
      Programs (Revision of the 2005 Training Guidelines for Pediatric Cardiology
      Fellowship Programs): Introduction.

PMID- 25777635
TI  - Task Force 5: Pediatric Cardiology Fellowship Training in Critical Care
      Cardiology.

PMID- 25777636
TI  - Task Force 8: Pediatric Cardiology Fellowship Training in Research and Scholarly
      Activity.

PMID- 25777637
TI  - 2015 SPCTPD/ACC/AAP/AHA Training Guidelines for Pediatric Cardiology Fellowship
      Programs (Revision of the 2005 Training Guidelines for Pediatric Cardiology
      Fellowship Programs).

PMID- 25777639
TI  - COCATS 4 Task Force 14: Training in the Care of Adult Patients With Congenital
      Heart Disease.

PMID- 25777638
TI  - COCATS 4 Task Force 11: Training in Arrhythmia Diagnosis and Management, Cardiac
      Pacing, and Electrophysiology.

PMID- 25777640
TI  - COCATS 4 Task Force 6: Training in Nuclear Cardiology.

PMID- 25777641
TI  - COCATS 4 Task Force 10: Training in Cardiac Catheterization.

PMID- 25777642
TI  - COCATS 4 Task Force 8: Training in Cardiovascular Magnetic Resonance Imaging.

PMID- 25777643
TI  - COCATS 4 Introduction.

PMID- 25777644
TI  - COCATS 4 Task Force 12: Training in Heart Failure.

PMID- 25777645
TI  - COCATS 4 Task Force 15: Training in Cardiovascular Research and Scholarly
      Activity.

PMID- 25777646
TI  - COCATS 4 Task Force 3: Training in Electrocardiography, Ambulatory
      Electrocardiography, and Exercise Testing.

PMID- 25777647
TI  - COCATS 4 Task Force 1: Training in Ambulatory, Consultative, and Longitudinal
      Cardiovascular Care.

PMID- 25777648
TI  - COCATS 4 Task Force 4: Training in Multimodality Imaging.

PMID- 25777649
TI  - COCATS 4 Task Force 13: Training in Critical Care Cardiology.

PMID- 25777650
TI  - COCATS 4 Task Force 7: Training in Cardiovascular Computed Tomographic Imaging.

PMID- 25777651
TI  - COCATS 4 Task Force 2: Training in Preventive Cardiovascular Medicine.

PMID- 25777653
TI  - COCATS 4 Task Force 9: Training in Vascular Medicine.

PMID- 25777654
TI  - Task Force 7: Pediatric Cardiology Fellowship Training in Pulmonary Hypertension,
      Advanced Heart Failure, and Transplantation.

PMID- 25777655
TI  - Idiopathic myointimal hyperplasia of mesenteric veins: Rare case of ischemic
      colitis mimicking inflammatory bowel disease.
AB  - Idiopathic myointimal hyperplasia of mesenteric veins (IMHMV) is a rare and
      poorly understood ischemic colitis that occurs in the rectosigmoid colon of
      predominantly young, previously healthy, male patients. A 76-year-old Japanese
      man presented to our hospital with a 1-year history of worsening diarrhea, lower
      abdominal pain, and weight loss (-6 kg). Laboratory evaluation revealed white
      blood cell count of 13,200/MUL, C-reactive protein level of 2.0 mg/dL (normal
      range, 0.0-0.3), and negative results for stool culture (including Clostridium
      difficile). Colonoscopy showed circumferential and edematous narrowing of the
      sigmoid colon with deep longitude ulceration. Biopsy was done and examination of
      the specimen demonstrated no specific ischemia. The patient was treated with
      bowel rest, antibiotics, and i.v. fluids; however, his symptoms worsened.
      Finally, sigmoidectomy was carried out. Histological examination demonstrated
      significant myointimal hyperplasia of mesenteric veins leading to thickening and
      stenosis of the venous lumen. Therefore, the final diagnosis was IMHMV. Three
      months following sigmoidectomy, he was asymptomatic.

PMID- 25777656
TI  - A Methodology of Analysis for Monitoring Treatment Progression with 19-Channel Z
      Score Neurofeedback (19ZNF) in a Single-Subject Design.
AB  - 19-Channel Z-Score Neurofeedback (19ZNF) is a modality using 19-electrodes with
      real-time normative database z-scores, suggesting effective clinical outcomes in
      fewer sessions than traditional neurofeedback. Thus, monitoring treatment
      progression and clinical outcome is necessary. The area of focus in this study
      was a methodology of quantitative analysis for monitoring treatment progression
      and clinical outcome with 19ZNF. This methodology is noted as the Sites-of
      Interest, which included repeated measures analyses of variance (rANOVA) and t
      tests for z-scores; it was conducted on 10 cases in a single subject design. To
      avoid selection bias, the 10 sample cases were randomly selected from a pool of
      17 cases that met the inclusion criteria. Available client outcome measures
      (including self-report) are briefly discussed. The results showed 90% of the pre
      post comparisons moved in the targeted direction (z = 0) and of those, 96% (80%
      Bonferroni corrected) of the t-tests and 96% (91% Bonferroni corrected) of the
      rANOVAs were statistically significant; thus indicating a progression towards the
      mean in 15 or fewer 19ZNF sessions. All cases showed and reported improvement in
      all outcome measures (including quantitative electroencephalography assessment)
      at case termination.

PMID- 25777657
TI  - Escaping the Golden Cage: Animal Models of Eating Disorders in the Post
      Diagnostic and Statistical Manual Era.
AB  - Eating disorders (EDs) are severe, life-threatening mental illnesses
      characterized by marked disturbances in body image and eating patterns. Attempts
      to understand the neurobiological basis of EDs have been hindered by the
      perception that EDs are primarily socially reinforced behaviors and not the
      result of a pathophysiologic process. This view is reflected by the diagnostic
      criteria of anorexia nervosa and bulimia nervosa, which emphasize intrapsychic
      conflicts such as "inability to maintain body weight," "undue influence of body
      weight or shape on self-evaluation," and "denial of the seriousness of low body
      weight" over neuropsychological measures. The neuropsychological constructs
      introduced within the research domain criteria (RDoC) matrix offer new hope for
      determining the neural substrate underlying the biological predisposition to EDs.
      We present selected studies demonstrating deficits in patients with EDs within
      each domain of the RDoC and propose a set of behavioral tasks in model systems
      that reflect aspects of that deficit. Finally, we propose a battery of tasks to
      examine comprehensively the function of neural circuits relevant to the
      development of EDs.

PMID- 25777658
TI  - Involvement of reductases IruO and NtrA in iron acquisition by Staphylococcus
      aureus.
AB  - To obtain host iron, Staphylococcus aureus secretes siderophores staphyloferrin A
      (SA) or staphyloferrin B (SB), and accesses heme iron through use of iron
      regulated surface determinant proteins. While iron transport in S. aureus is well
      documented, there is scant information about proteins required to access iron
      from complexes in the cytoplasm. In vitro studies identified a pyridine
      nucleotide-disulfide oxidoreductase, named IruO, as an electron donor for the
      heme monooxygenases IsdG and IsdI, promoting heme degradation. Here, we show that
      an iruO mutant was not debilitated for growth on heme, suggesting involvement of
      another reductase. NtrA is an iron-regulated nitroreductase and, as with the iruO
      mutant, a ntrA mutant grew on heme comparable with wild type (WT). In contrast, a
      iruO ntrA double mutant was severely debilitated for growth on heme, a phenotype
      that was complemented by expression of either iruO or ntrA in trans,
      demonstrating their overlapping role in heme-iron utilization. Contrasting the
      involvement of multiple reductases for heme iron utilization, ntrA was shown
      essential for iron utilization using SA, although not SB or other siderophores
      tested, and an iruO mutant was incapable of deferoxamine-mediated growth.
      Accordingly, virulence of WT S. aureus, but not an iruO mutant, was enhanced in
      mice receiving deferoxamine. 

PMID- 25777659
TI  - The challenge arising from open access.

PMID- 25777660
TI  - Eliminating acute kidney injury by 2025: an achievable goal.

PMID- 25777662
TI  - Pharmacology of antithrombotic drugs: an assessment of oral antiplatelet and
      anticoagulant treatments.
AB  - Antithrombotic drugs, which include antiplatelet and anticoagulant therapies,
      prevent and treat many cardiovascular disorders and, as such, are some of the
      most commonly prescribed drugs worldwide. The first drugs designed to inhibit
      platelets or coagulation factors, such as the antiplatelet clopidogrel and the
      anticoagulant warfarin, significantly reduced the risk of thrombotic events at
      the cost of increased bleeding in patients. However, both clopidogrel and
      warfarin have some pharmacological limitations including interpatient variability
      in antithrombotic effects in part due to the metabolism, interactions (eg, drug,
      environment, and genetic), or targets of the drugs. Increased knowledge of the
      pharmacology of antithrombotic drugs and the mechanisms underlying thrombosis has
      led to the development of newer drugs with faster onset of action, fewer
      interactions, and less interpatient variability in their antithrombotic effects
      than previous antithrombotic drugs. Treatment options now include the next
      generation antiplatelet drugs prasugrel and ticagrelor, and, in terms of
      anticoagulants, inhibitors that directly target factor IIa (dabigatran) or Xa
      (rivaroxaban, apixaban, edoxaban) are available. In this Series paper we review
      the pharmacological properties of these most commonly used oral antithrombotic
      drugs, and explore the development of antiplatelet and anticoagulant therapies. 

PMID- 25777661
TI  - International Society of Nephrology's 0by25 initiative for acute kidney injury
      (zero preventable deaths by 2025): a human rights case for nephrology.

PMID- 25777663
TI  - Clinical evidence for oral antiplatelet therapy in acute coronary syndromes.
AB  - Platelet-mediated thrombosis is a major pathophysiological mechanism that
      underlies acute coronary syndromes, and therefore, antiplatelet therapy is an
      important foundation in the treatment and prevention of recurrence of these
      syndromes. Nearly 30 years ago, aspirin was the first agent to show a benefit for
      acute coronary syndromes and is still a key therapeutic agent. The landmark CURE
      trial showed that the addition of a P2Y12 antagonist, clopidogrel, to aspirin was
      beneficial in the treatment of acute coronary syndromes. Despite substantial
      benefits with clopidogrel, limitations include the slow speed of onset, variable
      response, and a modest antiplatelet effect. Next-generation P2Y12 antagonists,
      prasugrel and ticagrelor, overcome these limitations and have been shown, in
      large-scale clinical trials for acute coronary syndromes, to reduce ischaemic
      events more than clopidogrel, at the expense of an increase in bleeding.
      Additional agents that target platelets by alternate mechanisms, including the
      protease-activated receptor-1 antagonist vorapaxar, have shown ischaemic benefit.
      These large-scale trials inform treatment decisions that need to balance
      ischaemic benefit and bleeding risk in patients with acute coronary syndromes.
      This Series paper describes major trial results, implications for clinical
      practice, and summarises continuing controversy. 

PMID- 25777664
TI  - Prolonged antiplatelet therapy after drug-eluting stents.

PMID- 25777665
TI  - Worldwide access to treatment for end-stage kidney disease: a systematic review.
AB  - BACKGROUND: End-stage kidney disease is a leading cause of morbidity and
      mortality worldwide. Prevalence of the disease and worldwide use of renal
      replacement therapy (RRT) are expected to rise sharply in the next decade. We
      aimed to quantify estimates of this burden. METHODS: We systematically searched
      Medline for observational studies and renal registries, and contacted national
      experts to obtain RRT prevalence data. We used Poisson regression to estimate the
      prevalence of RRT for countries without reported data. We estimated the gap
      between needed and actual RRT, and projected needs to 2030. FINDINGS: In 2010,
      2.618 million people received RRT worldwide. We estimated the number of patients
      needing RRT to be between 4.902 million (95% CI 4.438-5.431 million) in our
      conservative model and 9.701 million (8.544-11.021 million) in our high-estimate
      model, suggesting that at least 2.284 million people might have died prematurely
      because RRT could not be accessed. We noted the largest treatment gaps in low
      income countries, particularly Asia (1.907 million people needing but not
      receiving RRT; conservative model) and Africa (432,000 people; conservative
      model). Worldwide use of RRT is projected to more than double to 5.439 million
      (3.899-7.640 million) people by 2030, with the most growth in Asia (0.968 million
      to a projected 2.162 million [1.571-3.014 million]). INTERPRETATION: The large
      number of people receiving RRT and the substantial number without access to it
      show the need to both develop low-cost treatments and implement effective
      population-based prevention strategies. FUNDING: Australian National Health and
      Medical Research Council.

PMID- 25777666
TI  - Oral anticoagulants for stroke prevention in atrial fibrillation: current status,
      special situations, and unmet needs.
AB  - In patients with non-valvular atrial fibrillation, oral anticoagulation with
      vitamin K antagonists reduces the risk of stroke by more than 60%. But vitamin K
      antagonists have limitations, including causing serious bleeding such as
      intracranial haemorrhage and the need for anticoagulation monitoring. In part
      related to these limitations, they are used in only about half of patients who
      should be treated according to guideline recommendations. In the past decade,
      oral agents have been developed that directly block the activity of thrombin
      (factor IIa), as well as drugs that directly inhibit activated factor X (Xa),
      which is the first protein in the final common pathway to the activation of
      thrombin. These novel non-vitamin K antagonist oral anticoagulants (NOACs) have
      been shown to be at least as good as warfarin for stroke prevention in atrial
      fibrillation and they have proved to have better safety profiles. Their net
      advantage is underscored by significantly lower all-cause mortality compared with
      warfarin in large clinical trials. Because of these features and their ease of
      use, they are recommended for stroke prevention in atrial fibrillation. They have
      also a fast onset and offset of action, but they currently lack specific
      antidotes. This paper addresses the role of anticoagulation for stroke prevention
      in atrial fibrillation in the era of NOACs, with a focus on special situations
      including management in the event of bleeding and around the time of procedures
      including cardioversion, catheter ablation, and device implantation. Also their
      use in patients with concomitant coronary artery disease, with advanced age, with
      chronic kidney disease, or with valvular heart disease will be discussed as well
      as the interaction of NOACs with other cardiac medication, and switching between
      anticoagulants. 

PMID- 25777667
TI  - Mortality in patients treated with extended duration dual antiplatelet therapy
      after drug-eluting stent implantation: a pairwise and Bayesian network meta
      analysis of randomised trials.
AB  - BACKGROUND: Despite recent studies, the optimum duration of dual antiplatelet
      therapy (DAPT) after coronary drug-eluting stent placement remains uncertain. We
      performed a meta-analysis with several analytical approaches to investigate
      mortality and other clinical outcomes with different DAPT strategies. METHODS: We
      searched Medline, Embase, Cochrane databases, and proceedings of international
      meetings on Nov 20, 2014, for randomised controlled trials comparing different
      DAPT durations after drug-eluting stent implantation. We extracted study design,
      inclusion and exclusion criteria, sample characteristics, and clinical outcomes.
      DAPT duration was categorised in each study as shorter versus longer, and as 6
      months or shorter versus 1 year versus longer than 1 year. Analyses were done by
      both frequentist and Bayesian approaches. FINDINGS: We identified ten trials
      published between Dec 16, 2011, and Nov 16, 2014, including 31,666 randomly
      assigned patients. By frequentist pairwise meta-analysis, shorter DAPT was
      associated with significantly lower all-cause mortality compared with longer DAPT
      (HR 0.82, 95% CI 0.69-0.98; p=0.02; number needed to treat [NNT]=325), with no
      significant heterogeneity apparent across trials. The reduced mortality with
      shorter compared with longer DAPT was attributable to lower non-cardiac mortality
      (0.67, 0.51-0.89; p=0.006; NNT=347), with similar cardiac mortality (0.93, 0.73
      1.17; p=0.52). Shorter DAPT was also associated with a lower risk of major
      bleeding, but a higher risk of myocardial infarction and stent thrombosis. We
      noted similar results in a Bayesian framework with non-informative priors. By
      network meta-analysis, patients treated with 6-month or shorter DAPT and 1-year
      DAPT had higher risk of myocardial infarction and stent thrombosis but lower risk
      of mortality compared with patients treated with DAPT for longer than 1 year.
      Patients treated with DAPT for 6 months or shorter had similar rates of
      mortality, myocardial infarction, and stent thrombosis, but lower rates of major
      bleeding than did patients treated with 1-year DAPT. INTERPRETATION: Although
      treatment with DAPT beyond 1 year after drug-eluting stent implantation reduces
      myocardial infarction and stent thrombosis, it is associated with increased
      mortality because of an increased risk of non-cardiovascular mortality not offset
      by a reduction in cardiac mortality. FUNDING: None.

PMID- 25777668
TI  - Disparities in worldwide treatment of kidney failure.

PMID- 25777669
TI  - Update of the results of the Spanish branch of the European Randomized Study on
      Screening for Prostate Cancer (ERSPC).
AB  - OBJECTIVE: The role of prostate cancer (PC) screening is currently being
      questioned. The objective of the European Randomized Study of Screening for
      Prostate Cancer (ERSPC) was to demonstrate whether PC screening reduced mortality
      from this disease. The results from the Spanish branch of this study are
      presented: all-cause and cancer-specific mortality, the characteristics of the
      detected tumors, primary treatments and progression to advanced disease. MATERIAL
      AND METHODS: A total of 18,612 men, between the ages of 45 and 70, were invited
      to participate in the study, excluding those with a life expectancy of less than
      10 years. The men were randomized to the screening arm (serum prostate-specific
      antigen [PSA] reading) or the control arm (no diagnostic tests). Randomized
      transrectal ultrasound-guided sextant prostate biopsies were indicated for the
      men in the screening arm with PSA levels >=3ng/ml. The detected PCs were
      identified (stage and primary treatment), as well as the deaths that occurred
      (date and cause of death). RESULTS: The study was performed with 4276 men (2415
      in the screening arm and 1861 in the control arm). The median age and serum PSA
      level were 57 years and 0.90ng/mL, respectively. The median follow-up time was
      15.8 years. A total of 242 PCs were diagnosed, 162 (6.7%) in the screening arm
      and 80 (4.3%) in the control arm (P<.001). Of these, 214 (88.4%) had an organ
      confined clinical stage at onset (91.4% in the screening arm vs. 82.5% in the
      control arm; P=.024). A total of 112 patients (46.3%) underwent radical
      prostatectomy, 53 (21.9%) underwent prostate radiation therapy, 24 (9.9%)
      underwent hormone therapy and 47 (19.4%) were kept under observation. A total of
      18 PCs progressed to advanced disease (M+ or PSA levels >100ng/mL), with no
      differences between the study arms (P=.938). A total of 618 (14.5%) patients died
      during follow-up: 340 (14.1%) in the screening arm and 278 (14.9%) in the control
      arm, with no differences between the arms in terms of cancer-specific (P=.907) or
      all-cause (P=.399) mortality. The main causes of death were neoplasia (54.0%),
      cardiovascular (17.6%), respiratory (8.7%) and gastrointestinal (4.0%), with no
      difference between study arms. Of the 334 patients who died from neoplasia, only
      12 (3.6%) died from PC. CONCLUSIONS: PC screening results in a shifting of the
      diagnosis towards earlier stages. Nevertheless, we have not demonstrated a
      benefit in terms of overall or cancer-specific survival after more than 15 years
      of follow-up. The low mortality from this disease in our community could be one
      of the main factors that explain these results.

PMID- 25777670
TI  - Highly chlorinated unintentionally produced persistent organic pollutants
      generated during the methanol-based production of chlorinated methanes: A case
      study in China.
AB  - The formation of unintentionally produced persistent organic pollutants (POPs)
      may occur during various chlorination processes. In this study, emissions of
      unintentionally produced POPs during the methanol-based production of chlorinated
      methanes were investigated. High concentrations of highly chlorinated compounds
      such as decachlorobiphenyl, octachloronaphthalene, octachlorostyrene,
      hexachlorobutadiene, hexachlorocyclopentadiene, hexachlorobenzene, and
      pentachlorobenzene were found in the carbon tetrachloride byproduct of the
      methanol-based production of chlorinated methanes. The total emission amounts of
      hexachlorocyclopentadiene, hexachlorobutadiene, polychlorinated benzenes,
      polychlorinated naphthalenes, octachlorostyrene, and polychlorinated biphenyls
      released during the production of chlorinated methanes in China in 2010 were
      estimated to be 10080, 7350, 5210, 427, 212, and 167 kg, respectively. Moreover,
      polychlorinated dibenzo-p-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs)
      were formed unintentionally during chlorinated methanes production, the emission
      factor for PCDDs/DFs was 364 MUg toxic equivalency quotient (TEQ) t(-1) product
      for residues, which should be added into the UNEP toolkit for updating. It was
      worth noting that a high overall toxic equivalency quotient from polychlorinated
      naphthalenes and PCDDs/DFs was generated from the chlorinated methanes production
      in China in 2010. The values reached 563 and 32.8 g TEQ, respectively. The
      results of the study indicate that more research and improved management systems
      are needed to ensure that the methanol-based production of chlorinated methanes
      can be achieved safely.

PMID- 25777671
TI  - The Sinorhizobium meliloti SyrM regulon: effects on global gene expression are
      mediated by syrA and nodD3.
AB  - In Sinorhizobium meliloti, three NodD transcriptional regulators activate
      bacterial nodulation (nod) gene expression. NodD1 and NodD2 require plant
      compounds to activate nod genes. The NodD3 protein does not require exogenous
      compounds to activate nod gene expression; instead, another transcriptional
      regulator, SyrM, activates nodD3 expression. In addition, NodD3 can activate syrM
      expression. SyrM also activates expression of another gene, syrA, which when
      overexpressed causes a dramatic increase in exopolysaccharide production. In a
      previous study, we identified more than 200 genes with altered expression in a
      strain overexpressing nodD3. In this work, we define the transcriptomes of
      strains overexpressing syrM or syrA. The syrM, nodD3, and syrA overexpression
      transcriptomes share similar gene expression changes; analyses imply that nodD3
      and syrA are the only targets directly activated by SyrM. We propose that most of
      the gene expression changes observed when nodD3 is overexpressed are due to NodD3
      activation of syrM expression, which in turn stimulates SyrM activation of syrA
      expression. The subsequent increase in SyrA abundance results in broad changes in
      gene expression, most likely mediated by the ChvI-ExoS-ExoR regulatory circuit.
      IMPORTANCE: Symbioses with bacteria are prevalent across the animal and plant
      kingdoms. Our system of study, the rhizobium-legume symbiosis (Sinorhizobium
      meliloti and Medicago spp.), involves specific host-microbe signaling,
      differentiation in both partners, and metabolic exchange of bacterial fixed
      nitrogen for host photosynthate. During this complex developmental process, both
      bacteria and plants undergo profound changes in gene expression. The S. meliloti
      SyrM-NodD3-SyrA and ChvI-ExoS-ExoR regulatory circuits affect gene expression and
      are important for optimal symbiosis. In this study, we defined the transcriptomes
      of S. meliloti overexpressing SyrM or SyrA. In addition to identifying new
      targets of the SyrM-NodD3-SyrA regulatory circuit, our work further suggests how
      it is linked to the ChvI-ExoS-ExoR regulatory circuit.

PMID- 25777673
TI  - Structural determinants of the interaction between the TpsA and TpsB proteins in
      the Haemophilus influenzae HMW1 two-partner secretion system.
AB  - The two-partner secretion (TPS) pathway in Gram-negative bacteria consists of a
      TpsA exoprotein and a cognate TpsB outer membrane pore-forming translocator
      protein. Previous work has demonstrated that the TpsA protein contains an N
      terminal TPS domain that plays an important role in targeting the TpsB protein
      and is required for secretion. The nontypeable Haemophilus influenzae HMW1 and
      HMW2 adhesins are homologous proteins that are prototype TpsA proteins and are
      secreted by the HMW1B and HMW2B TpsB proteins. In the present study, we sought to
      define the structural determinants of HMW1 interaction with HMW1B during the
      transport process and while anchored to the bacterial surface. Modeling of HMW1B
      revealed an N-terminal periplasmic region that contains two polypeptide transport
      associated (POTRA) domains and a C-terminal membrane-localized region that forms
      a pore. Biochemical studies demonstrated that HMW1 engages HMW1B via interaction
      between the HMW1 TPS domain and the HMW1B periplasmic region, specifically, the
      predicted POTRA1 and POTRA2 domains. Subsequently, HMW1 is shuttled to the HMW1B
      pore, facilitated by the N-terminal region, the middle region, and the NPNG motif
      in the HMW1 TPS domain. Additional analysis revealed that the interaction between
      HMW1 and HMW1B is highly specific and is dependent upon the POTRA domains and the
      pore-forming domain of HMW1B. Further studies established that tethering of HMW1
      to the surface-exposed region of HMW1B is dependent upon the external loops of
      HMW1B formed by residues 267 to 283 and residues 324 to 330. These observations
      may have broad relevance to proteins secreted by the TPS pathway. IMPORTANCE:
      Secretion of HMW1 involves a recognition event between the extended form of the
      HMW1 propiece and the HMW1B POTRA domains. Our results identify specific
      interactions between the HMW1 propiece and the periplasmic HMW1B POTRA domains.
      The results also suggest that the process of HMW1 translocation involves at least
      two discrete steps, including initial interaction between the HMW1 propiece and
      the HMW1B POTRA domains and then a separate translocation event. We have also
      discovered that the HMW1B pore itself appears to influence the translocation
      process. These observations extend our knowledge of the two-partner secretion
      system and may be broadly relevant to other proteins secreted by the TPS pathway.

PMID- 25777672
TI  - Mutations in pneumococcal cpsE generated via in vitro serial passaging reveal a
      potential mechanism of reduced encapsulation utilized by a conjunctival isolate.
AB  - The polysaccharide capsule of Streptococcus pneumoniae is required for
      nasopharyngeal colonization and for invasive disease in the lungs, blood, and
      meninges. In contrast, the vast majority of conjunctival isolates are acapsular.
      The first serotype-specific gene in the capsule operon, cpsE, encodes the
      initiating glycosyltransferase and is one of the few serotype-specific genes that
      can tolerate null mutations. This report characterizes a spontaneously arising
      TIGR4 mutant exhibiting a reduced capsule, caused by a 6-nucleotide duplication
      in cpsE which results in duplication of Ala and Ile at positions 45 and 46. This
      strain (AI45dup) possessed more exposed phosphorylcholine and was
      hypersusceptible to C3 complement deposition compared to the wild type.
      Accordingly, the mutant was significantly better at forming abiotic biofilms and
      binding epithelial cells in vitro but was avirulent in a sepsis model. In vitro
      serial passaging of the wild-type strain failed to reproduce the AI45dup mutation
      but instead led to a variety of mutants with reduced capsule harboring single
      nucleotide polymorphisms (SNPs) in cpsE. A single passage in the sepsis model
      after high-dose inoculation readily yielded revertants of AI45dup with restored
      wild-type capsule level, but the majority of SNP alleles of cpsE could not
      revert, suppress, or bypass. Analysis of cpsE in conjunctival isolates revealed a
      strain with a single missense mutation at amino acid position 377, which was
      responsible for reduced encapsulation. This study supports the hypothesis that
      spontaneous, nonreverting mutations in cpsE serve as a form of adaptive mutation
      by providing a selective advantage to S. pneumoniae in niches where expression of
      capsule is detrimental. IMPORTANCE: While the capsule of Streptococcus pneumoniae
      is required for colonization and invasive disease, most conjunctival isolates are
      acapsular by virtue of deletion of the entire capsular operon. We show that
      spontaneous acapsular mutants isolated in vitro harbor mostly nonrevertible
      single nucleotide polymorphism (SNP) null mutations in cpsE, encoding the
      initiating glycosyltransferase. From a small collection of acapsular conjunctival
      isolates, we identified one strain with a complete capsular operon but containing
      a SNP in cpsE that we show is responsible for the acapsular phenotype. We propose
      that acapsular conjunctival isolates may arise initially from such nonreverting
      SNP null mutations in cpsE, which can be followed later by deletion of portions
      or all of the cps operon.

PMID- 25777674
TI  - Glutamate Racemase Mutants of Bacillus anthracis.
AB  - D-Glutamate is an essential component of bacterial peptidoglycan and a building
      block of the poly-gamma-D-glutamic acid (PDGA) capsule of Bacillus anthracis, the
      causative agent of anthrax. Earlier work suggested that two glutamate racemases,
      encoded by racE1 and racE2, are each essential for growth of B. anthracis,
      supplying D-glutamic acid for the synthesis of peptidoglycan and PDGA capsule.
      Earlier work could not explain, however, why two enzymes that catalyze the same
      reaction may be needed for bacterial growth. Here, we report that deletion of
      racE1 or racE2 did not prevent growth of B. anthracis Sterne (pXO1(+) pXO2(-)),
      the noncapsulating vaccine strain, or of B. anthracis Ames (pXO1(+) pXO2(+)), a
      fully virulent, capsulating isolate. While mutants with deletions in racE1 and
      racE2 were not viable, racE2 deletion delayed vegetative growth of B. anthracis
      following spore germination and caused aberrant cell shapes, phenotypes that were
      partially restored by exogenous D-glutamate. Deletion of racE1 or racE2 from B.
      anthracis Ames did not affect the production or stereochemical composition of the
      PDGA capsule. A model is presented whereby B. anthracis, similar to Bacillus
      subtilis, utilizes two functionally redundant racemase enzymes to synthesize D
      glutamic acid for peptidoglycan synthesis. IMPORTANCE: Glutamate racemases,
      enzymes that convert L-glutamate to D-glutamate, are targeted for antibiotic
      development. Glutamate racemase inhibitors may be useful for the treatment of
      bacterial infections such as anthrax, where the causative agent, B. anthracis,
      requires d-glutamate for the synthesis of peptidoglycan and poly-gamma-D-glutamic
      acid (PDGA) capsule. Here we show that B. anthracis possesses two glutamate
      racemase genes that can be deleted without abolishing either bacterial growth or
      PDGA synthesis. These data indicate that drug candidates must inhibit both
      glutamate racemases, RacE1 and RacE2, in order to block B. anthracis growth and
      achieve therapeutic efficacy.

PMID- 25777675
TI  - Structure-function analysis of peptide signaling in the Clostridium perfringens
      Agr-like quorum sensing system.
AB  - The accessory growth regulator (Agr)-like quorum sensing (QS) system of
      Clostridium perfringens controls the production of many toxins, including beta
      toxin (CPB). We previously showed (J. E. Vidal, M. Ma, J. Saputo, J. Garcia, F.
      A. Uzal, and B. A. McClane, Mol Microbiol 83:179-194, 2012,
      http://dx.doi.org/10.1111/j.1365-2958.2011.07925.x) that an 8-amino-acid, AgrD
      derived peptide named 8-R upregulates CPB production by this QS system. The
      current study synthesized a series of small signaling peptides corresponding to
      sequences within the C. perfringens AgrD polypeptide to investigate the C.
      perfringens autoinducing peptide (AIP) structure-function relationship. When both
      linear and cyclic ring forms of these peptides were added to agrB null mutants of
      type B strain CN1795 or type C strain CN3685, the 5-amino-acid peptides, whether
      in a linear or ring (thiolactone or lactone) form, induced better signaling (more
      CPB production) than peptide 8-R for both C. perfringens strains. The 5-mer
      thiolactone ring peptide induced faster signaling than the 5-mer linear peptide.
      Strain-related variations in sensing these peptides were detected, with CN3685
      sensing the synthetic peptides more strongly than CN1795. Consistent with those
      synthetic peptide results, Transwell coculture experiments showed that CN3685
      exquisitely senses native AIP signals from other isolates (types A, B, C, and D),
      while CN1795 barely senses even its own AIP. Finally, a C. perfringens AgrD
      sequence-based peptide with a 6-amino-acid thiolactone ring interfered with CPB
      production by several C. perfringens strains, suggesting potential therapeutic
      applications. These results indicate that AIP signaling sensitivity and
      responsiveness vary among C. perfringens strains and suggest C. perfringens
      prefers a 5-mer AIP to initiate Agr signaling. IMPORTANCE: Clostridium
      perfringens possesses an Agr-like quorum sensing (QS) system that regulates
      virulence, sporulation, and toxin production. The current study used synthetic
      peptides to identify the structure-function relationship for the signaling
      peptide that activates this QS system. We found that a 5-mer peptide induces
      optimal signaling. Unlike other Agr systems, a linear version of this peptide (in
      addition to thiolactone and lactone versions) could induce signaling. Two C.
      perfringens strains were found to vary in sensitivity to these peptides. We also
      found that a 6-mer peptide can inhibit toxin production by some strains,
      suggesting therapeutic applications.

PMID- 25777676
TI  - Efficient assembly of ribosomes is inhibited by deletion of bipA in Escherichia
      coli.
AB  - The bacterial BipA protein belongs to the EF-G family of translational GTPases
      and has been postulated to be either a regulatory translation factor or a
      ribosome assembly factor. To distinguish between these hypotheses, we analyzed
      the effect of bipA deletion on three phenotypes associated with ribosome assembly
      factors: cold sensitivity, ribosome subunit distribution, and rRNA processing. We
      demonstrated that a DeltabipA strain exhibits a cold-sensitive phenotype that is
      similar to, and synergistic with, that of a strain with a known ribosome assembly
      factor, deaD. Additionally, the bipA deletion strain displayed a perturbed
      ribosome subunit distribution when grown at low temperature, similar to that of a
      deaD mutant, and again, the double mutant showed additive effects. The primary
      ribosomal deficiency noted was a decreased level of the 50S subunit and the
      appearance of a presumed pre-50S particle. Finally, deletion of bipA resulted in
      accumulation of pre23S rRNA, as did deletion of deaD. We further found that
      deletion of rluC, which encodes a pseudouridine synthase that modifies the 23S
      rRNA at three sites, suppressed all three phenotypes of the bipA mutant,
      supporting and extending previous findings. Together, these results suggest that
      BipA is important for the correct and efficient assembly of the 50S subunit of
      the ribosome at low temperature but when unmodified by RluC, the ribosomes become
      BipA independent for assembly. IMPORTANCE: The ribosome is the complex
      ribonucleoprotein machine responsible for protein synthesis in all cells.
      Although much has been learned about the structure and function of the ribosome,
      we do not fully understand how it is assembled or the accessory proteins that
      increase efficiency of biogenesis and function. This study examined one such
      protein, BipA. Our results indicate that BipA either directly or indirectly
      enhances the formation of the 50S subunit of the ribosome, particularly at low
      temperature. In addition, ribosomes contain a large number of modified
      nucleosides, including pseudouridines. This work demonstrates that the function
      of BipA is tied to the modification status of the ribosome and may help us
      understand why these modifications have been retained.

PMID- 25777677
TI  - Neisseria gonorrhoeae MutS affects pilin antigenic variation through mismatch
      correction and not by pilE guanine quartet binding.
AB  - Many pathogens use homologous recombination to vary surface antigens to avoid
      immune surveillance. Neisseria gonorrhoeae achieves this in part by changing the
      properties of its surface pili in a process called pilin antigenic variation
      (AV). Pilin AV occurs by high-frequency gene conversion reactions that transfer
      silent pilS sequences into the expressed pilE locus and requires the formation of
      an upstream guanine quartet (G4) DNA structure to initiate this process. The MutS
      and MutL proteins of the mismatch correction (MMC) system act to correct
      mismatches after replication and prevent homeologous (i.e., partially homologous)
      recombination, but MutS orthologs can also bind to G4 structures. A previous
      study showed that mutation of MutS resulted in a 3-fold increase in pilin AV,
      which could be due to the loss of MutS antirecombination properties or loss of G4
      binding. We tested two site-directed separation-of-function MutS mutants that are
      both predicted to bind to G4s but are not able to perform MMC. Pilus phase
      variation assays and DNA sequence analysis of pilE variants produced in these
      mutants showed that all three mutS mutants and a mutL mutant had similar
      increased frequencies of pilin AV. Moreover, the mutS mutants all showed similar
      increased levels of pilin AV-dependent synthetic lethality. These results show
      that antirecombination by MMC is the reason for the effect that MutS has on pilin
      AV and is not due to pilE G4 binding by MutS. IMPORTANCE: Neisseria gonorrhoeae
      continually changes its outer surface proteins to avoid recognition by the immune
      system. N. gonorrhoeae alters the antigenicity of the pilus by directed
      recombination between partially homologous pilin copies in a process that
      requires a guanine quartet (G4) structure. The MutS protein of the mismatch
      correction (MMC) system prevents recombination between partially homologous
      sequences and can also bind to G4s. We confirmed that loss of MMC increases the
      frequency of pilin antigenic variation and that two MutS mutants that are
      predicted to separate the two different functions of MutS inhibit pilin variation
      similarly to a complete-loss-of-function mutant, suggesting that interaction of
      MutS with the G4 structure is not a major factor in this process.

PMID- 25777678
TI  - A cluster of four homologous small RNAs modulates C1 metabolism and the pyruvate
      dehydrogenase complex in Rhodobacter sphaeroides under various stress conditions.
AB  - In bacteria, regulatory RNAs play an important role in the regulation and
      balancing of many cellular processes and stress responses. Among these regulatory
      RNAs, trans-encoded small RNAs (sRNAs) are of particular interest since one sRNA
      can lead to the regulation of multiple target mRNAs. In the purple bacterium
      Rhodobacter sphaeroides, several sRNAs are induced by oxidative stress. In this
      study, we focused on the functional characterization of four homologous sRNAs
      that are cotranscribed with the gene for the conserved hypothetical protein
      RSP_6037, a genetic arrangement described for only a few sRNAs until now. Each of
      the four sRNAs is characterized by two stem-loops that carry CCUCCUCCC motifs in
      their loops. They are induced under oxidative stress, as well as by various other
      stress conditions, and were therefore renamed here sRNAs CcsR1 to CcsR4 (CcsR1-4)
      for conserved CCUCCUCCC motif stress-induced RNAs 1 to 4. Increased CcsR1-4
      expression decreases the expression of genes involved in C1 metabolism or
      encoding components of the pyruvate dehydrogenase complex either directly by
      binding to their target mRNAs or indirectly. One of the CcsR1-4 target mRNAs
      encodes the transcriptional regulator FlhR, an activator of glutathione-dependent
      methanol/formaldehyde metabolism. Downregulation of this glutathione-dependent
      pathway increases the pool of glutathione, which helps to counteract oxidative
      stress. The FlhR-dependent downregulation of the pyruvate dehydrogenase complex
      reduces a primary target of reactive oxygen species and reduces aerobic electron
      transport, a main source of reactive oxygen species. Our findings reveal a
      previously unknown strategy used by bacteria to counteract oxidative stress.
      IMPORTANCE: Phototrophic organisms have to cope with photo-oxidative stress due
      to the function of chlorophylls as photosensitizers for the formation of singlet
      oxygen. Our study assigns an important role in photo-oxidative stress resistance
      to a cluster of four homologous sRNAs in the anoxygenic phototrophic bacterium
      Rhodobacter sphaeroides. We reveal a function of these regulatory RNAs in the
      fine-tuning of C1 metabolism. A model that relates oxidative stress defense to C1
      metabolism is presented.

PMID- 25777679
TI  - Characterization of the microbial diversity in yacon spontaneous fermentation at
      20  degrees C.
AB  - The prebiotic fructooligosaccharide content of yacon makes this root an
      attractive alternative for the supplementation of a variety of food products. The
      preservation of yacon by fermentation has been proposed as an alternative to
      increase the probiotic content of the root concomitantly with its shelf life.
      Thus the fermented yacon could have significant functional content. The objective
      of this research was to characterize the biochemistry and microbiology of
      spontaneous yacon fermentation with 2% NaCl and define the viability of the
      proposed process. The biochemical analysis of spontaneous heterolactic
      fermentation of yacon showed a progressive drop in pH with increased lactic and
      acetic acids, and the production of mannitol during fermentation. The microbial
      ecology of yacon fermentation was investigated using culture-dependent and
      culture-independent methods. Bacterial cell counts revealed a dominance of lactic
      acid bacteria (LAB) over yeasts, which were also present during the first 2 days
      of the fermentation. Results showed that the heterofermentative LAB were
      primarily Leuconostoc species, thus it presents a viable method to achieve long
      term preservation of this root.

PMID- 25777680
TI  - Stability of sublethal acid stress adaptation and induced cross protection
      against lauric arginate in Listeria monocytogenes.
AB  - The stability of acid stress adaptation in Listeria monocytogenes and its induced
      cross protection effect against GRAS (generally recognized as safe) antimicrobial
      compounds has never been investigated before. In the present study, the acid
      stress adaptation in L. monocytogenes was initially induced in pH 5.0 tryptic soy
      broth supplemented with 0.6% yeast extract (TSB-YE) at 37  degrees C.
      Subsequently, the stability of acid stress adaptation, which was defined as the
      capacity to maintain its acquired acid adaptation after induction in the absence
      of sublethal acid stress, was determined at 37  degrees C, 22  degrees C or 4 
      degrees C in broth and in different food substrates. Then, the acid stress
      adaptation induced cross protection against lauric arginate (LAE) and its
      stability was investigated in TSB-YE, milk and carrot juice. Our findings show
      that the acid stress adaptation was stable at 4  degrees C up to 24h but was
      reversed at 37  degrees C or 22  degrees C within 2h. In the cross protection
      assay with LAE, the acid stress adapted cells had approximately 2 log CFU/ml
      greater survival than non-adapted cells in broth at 22  degrees C or in milk and
      carrot juice at 4  degrees C. The acid adaptation induced cross protection
      against LAE in L. monocytogenes was reversible within 1h at 4  degrees C in the
      absence of sublethal acid stress. Our findings suggest that the stability of acid
      adaptation in L. monocytogenes under cold conditions should be taken into account
      when the risk analysis is performed during food processing.

PMID- 25777681
TI  - A Population-Based Study of Men With Low-Volume Low-Risk Prostate Cancer: Does
      African-American Race Predict for More Aggressive Disease?
AB  - BACKGROUND: Because of recent reports that suggested more pathologically
      aggressive disease in African-American (AA) men, we sought to compare pathologic
      features between AA and Caucasian-American men with low-risk, low-volume prostate
      cancer. MATERIALS AND METHODS: We analyzed the Surveillance, Epidemiology, and
      End Results database for pathologic differences based on race. Data on all men
      who were diagnosed between 2010 and 2011 with prostate cancer, T1cN0M0, Gleason
      score of 6 (3+3), prostate-specific antigen < 10 ng/mL, via a 12-core biopsy and
      had <= 2 positive samples, and underwent radical prostatectomy were abstracted.
      Univariate and multivariate logistic regression were performed to detect
      predictors for adverse pathology, which was primarily defined as pT2 and Gleason
      >= 4+3, or pT3a and Gleason 3+3 with positive margins, pT3a and Gleason >= 3+4,
      or pT3b-pT4 with any Gleason score. RESULTS: There were 1794 men who met the
      target study criteria. AA men were a median of 3 years younger (P < .001), and
      were more likely to have 2 positive cores (P = .02). However, there were no
      statistically significant differences between Caucasian and AA men regarding
      pathologic Gleason score (P = .99), pathologic extent of disease (P = .34),
      margins (P = .43), Cancer of the Prostate Risk Assessment score (P = .56), or
      adverse features (P = .45). On multivariate analysis, there were no differences
      between AA and Caucasian men with regard to adverse pathologic features (odds
      ratio, 1.43; 95% confidence interval, 0.87-1.24; P = .16). CONCLUSION: In the
      absence of definitive data to support a more aggressive natural history of very
      low risk prostate cancer in AA men, these data support continued use of active
      surveillance in this population.

PMID- 25777682
TI  - Neutrophil-Lymphocyte Ratio and Pathological Response to Neoadjuvant Chemotherapy
      in Patients With Muscle-Invasive Bladder Cancer.
AB  - BACKGROUND: Cisplatin-based neoadjuvant chemotherapy (NC) improves overall
      survival in muscle-invasive bladder cancer (MIBC), but there are currently no
      predictive biomarkers of response to NC in MIBC. An increased peripheral blood
      neutrophil to lymphocyte ratio (NLR) is a marker of systemic inflammation and is
      linked to poor prognosis in some solid tumors. We evaluated whether NLR is
      associated with pathological response (pathR) in MIBC patients who receive NC.
      PATIENTS AND METHODS: MIBC patients treated with NC and radical cystectomy (RC)
      between July 2006 and April 2013 were retrospectively reviewed. The primary end
      point was to find variables associated with pathR in the RC specimen after NC.
      Potential predictive markers were analyzed using logistic regression. NLR values
      before NC, midway through NC, and before RC were collected and compared between
      patients who achieved pathR ('responders') and those who did not
      ('nonresponders'). RESULTS: In 26 evaluable patients, age, sex, performance
      status, smoking status, stage, hydronephrosis, NLR before NC, midway through NC,
      and before RC were not significantly associated with pathR, but the pattern of
      NLR change between responders and nonresponders was significantly different (P =
      .038). Responders exhibited a sustained decrease in NLR during NC until RC, and
      nonresponders exhibited a transient decrease in NLR which then increased to above
      its baseline before RC. CONCLUSION: The pattern of change in NLR during NC varied
      significantly between responders and nonresponders. We hypothesize that a
      sustained decrease in inflammatory burden during NC is associated with pathR.
      Despite limitations of a small retrospective study, our observations might have
      clinical implications and warrant further basic and clinical research.

PMID- 25777683
TI  - Cerebellar direct current stimulation modulates pain perception in humans.
AB  - PURPOSE: The cerebellum is involved in a wide number of integrative functions,
      but its role in pain experience and in the nociceptive information processing is
      poorly understood. In healthy volunteers we evaluated the effects of transcranial
      cerebellar direct current stimulation (tcDCS) by studying the changes in the
      perceptive threshold, pain intensity at given stimulation intensities (VAS:0-10)
      and laser evoked potentials (LEPs) variables (N1 and N2/P2 amplitudes and
      latencies). METHODS: Fifteen subjects were studied before and after anodal,
      cathodal and sham tcDCS. LEPs were obtained using a neodymium:yttrium-aluminium
      perovskite (Nd:YAP) laser and recorded from the dorsum of the left hand. VAS was
      evaluated by delivering laser pulses at two different intensities, respectively
      two and three times the perceptive threshold. RESULTS: Cathodal polarization
      dampened significantly the perceptive threshold and increased the VAS score,
      while the anodal one had opposite effects. Cathodal tcDCS increased significantly
      the N1 and N2/P2 amplitudes and decreased their latencies, whereas anodal tcDCS
      elicited opposite effects. Motor thresholds assessed through transcranial
      magnetic stimulation were not affected by cerebellar stimulation. CONCLUSIONS:
      tcDCS modulates pain perception and its cortical correlates. Since it is
      effective on both N1 and N2/P2 components, we speculate that the cerebellum
      engagement in pain processing modulates the activity of both somatosensory and
      cingulate cortices. Present findings prompt investigation of the cerebellar
      direct current polarization as a possible novel and safe therapeutic tool in
      chronic pain patients.

PMID- 25777684
TI  - Violence at work and depressive symptoms in primary health care teams: a cross
      sectional study in Brazil.
AB  - PURPOSE: Implementation of primary care has long been a priority in low- and
      middle-income countries. Violence at work may hamper progress in this field.
      Hence, we examined the associations between violence at work and depressive
      symptoms/major depression in primary care teams (physicians, nurses, nursing
      assistants, and community health workers). METHODS: A cross-sectional study was
      undertaken in the city of Sao Paulo, Brazil. We assessed a random sample of
      Family Health Program teams. We investigated depressive symptoms and major
      depression using the nine-item Patient Health Questionnaire (PHQ-9), and exposure
      to violence at work in the previous 12 months using a standardized questionnaire.
      Associations between exposure to violence and depressive symptoms/major
      depression were analyzed using multinomial logistic regression. RESULTS: Of 3141
      eligible workers, 2940 (93 %) completed the interview. Of these, 36.3 % (95 % CI
      34.6-38.1) presented intermediate depressive symptoms, and 16 % (95 % CI 14.6
      17.2), probable major depression. The frequencies of exposure to the different
      types of violence at work were: insults (44.9 %), threats (24.8 %), physical
      aggression (2.3 %), and witnessing violence (29.5 %). These exposures were
      strongly and progressively associated with depressive symptoms (adjusted odds
      ratio 1.67 for exposure to one type of violence; and 5.10 for all four types),
      and probable major depression (adjusted odds ratio 1.84 for one type; and 14.34
      for all four types). CONCLUSION: Primary care workers presenting depressive
      symptoms and those who have experienced violence at work should be assisted.
      Policy makers should prioritize strategies to prevent these problems, since they
      can threaten primary care sustainability.

PMID- 25777739
TI  - A fused meso-aminoporphyrin: a switchable near-IR chromophore.
AB  - An aryl amine attached to the meso position of a porphyrin controls the pi
      delocalization using a redox process or a protonation/deprotonation centered at
      the meso-nitrogen. An easily accessible modulated motif affords a switchable near
      IR chromophore as reflected by significant changes in absorption and fluorescence
      spectra. 

PMID- 25777685
TI  - Diagnosed thyroid disorders are associated with depression and anxiety.
AB  - PURPOSE: Associations between thyroid diseases and depression have been described
      since the 1960s but there is a lack of population-based studies investigating
      associations of thyroid diseases with depression and anxiety defined by gold
      standard methods. Thus, the aim was to investigate the association of diagnosed
      thyroid disorders, serum thyroid-stimulating hormone (TSH) levels, and anti
      thyroid-peroxidase antibodies (TPO-abs) with depression and anxiety. METHODS: We
      used data from 2142 individuals, who participated in the first follow-up of the
      Study of Health in Pomerania (SHIP-1) and in the Life-Events and Gene-Environment
      Interaction in Depression (LEGEND). DSM-VI diagnoses of major depression disorder
      and anxiety were defined using the Munich-Composite International Diagnostic
      Interview; the Beck depression inventory (BDI-II) was used for the assessment of
      current depressive symptoms. Thyroid diseases were assessed by interviews and by
      biomarkers and were associated with depression and anxiety using Poisson
      regression adjusted for age, sex, marital status, educational level, smoking
      status, BMI, and the log-transformed time between SHIP-1 and LEGEND. RESULTS:
      Untreated diagnosed hypothyroidism was positively associated with the BDI-II
      score and with anxiety, while untreated diagnosed hyperthyroidism was
      significantly related to MDD during the last 12 months. Serum TSH levels and TPO
      Abs were not significantly associated with depression and anxiety. In sub
      analyses, distinct interactions were found between childhood maltreatment and
      thyroid disorders in modifying the association on depression and anxiety
      disorders. CONCLUSIONS: Our results substantiate evidence that diagnosed
      untreated hypothyroidism is associated with depression and anxiety, and that
      diagnosed untreated hyperthyroidism is associated with depression.

PMID- 25777741
TI  - META: an MRI-based scoring system differentiating metastatic from osteoporotic
      vertebral fractures.
AB  - BACKGROUND CONTEXT: Magnetic resonance imaging (MRI) is useful for the
      differential diagnosis of osteoporotic vertebral fractures (OVFs) and metastatic
      vertebral fractures (MVFs), but no single finding is absolutely conclusive.
      PURPOSE: The purpose of the present study was to create a scoring system to
      facilitate the correct diagnosis of MVFs by integrating several MRI findings.
      STUDY DESIGN: This is a retrospective and single-center observational study that
      attempts to create a diagnostic scoring system by discriminant analysis. PATIENTS
      SAMPLE: We included 100 OVFs and 100 MVFs in thoracolumbar vertebrae of which MR
      images were obtained within 60 days from the suspected time of fractures. OUTCOME
      MEASURES: The sensitivity and specificity of known important MRI findings were
      assessed, and the classification accuracy of the scoring system was investigated.
      METHODS: Seven MRI findings of these fractures were analyzed to evaluate their
      sensitivity and specificity. Using these findings as variables, discriminant
      analysis was performed in 140 fractures as a training set, and the classification
      accuracy was calculated in the remaining 60 fractures as a test set.
      Additionally, the images of these 60 fractures were reviewed by another blinded
      reviewer to investigate the interobserver reliability of each finding. RESULTS:
      All findings had high specificity with low-to-moderate sensitivity. Eight
      variables were selected in the final discriminant function. A simpler scoring
      system (MRI Evaluation Totalizing Assessment [META]) was created by approximating
      the coefficients and the constant term by integral numbers. The classification
      accuracy was calculated to be 96.6% in the test set. The interobserver
      reliability of the key findings varied, but the final discrimination conducted by
      META had the high agreement between the two reviewers (kappa=0.93). CONCLUSIONS:
      This novel scoring system, META, could prove to be a useful tool for the
      differential diagnosis of OVFs and MVFs. It is simple and physician friendly, yet
      highly accurate.

PMID- 25777742
TI  - Characterization of lumbar spinous process morphology: a cadaveric study of 2,955
      human lumbar vertebrae.
AB  - BACKGROUND CONTEXT: Despite the interest in lumbar spinous process (SP)-based
      surgical innovation, there are no large published studies that have characterized
      the morphometry of lumbar SPs. PURPOSE: To provide accurate level-specific
      morphometric data with respect to human lumbar SPs using a human cadaveric lumbar
      spine model and to describe the morphometric variation of lumbar SPs with respect
      to gender, race, and age. STUDY DESIGN: An anatomic observational study. METHODS:
      This study used 2,955 cadaveric lumbar vertebrae from 591 adult spines at the
      Hamann-Todd Human Osteological Collection. Specimens were aged 20 to 79 years.
      Each vertebra was photographed in standardized positions and measured using
      ImageJ software. Direct measurements were made for the SP length, width, height,
      slope, and caudal morphology. Gender, race, and age were recorded and analyzed.
      RESULTS: Spinous process length was 24.8+/-4.6 mm (L5) to 33.9+/-3.9 mm (L3).
      Effective length varied from 19.5+/-2.6 mm (L1) to 24.6+/-3.3 mm (L4). Height was
      shortest at L5 (18.2+/-2.7 mm). Caudal width was greater than the cranial width.
      Slope, caudal morphology, and radius measures showed large interspecimen
      variation. Slope at L5 was steeper than other levels (23.7 degrees +/-10.5
      degrees , p<.0001). Most specimens demonstrated convex caudal morphology. L4 had
      the highest proportion of convexity (80.7%). L1 was the only level with
      predominantly concave morphology. Measurements for female SPs were smaller, but
      the slope was steeper. Anatomic and effective SP lengths were longer for
      specimens from white individuals. Specimens from black individuals had larger
      width and height, as well as steeper slope. Black specimens had more convex
      morphology at L4 and L5. With increasing age, the SP length, effective length,
      and width increased. Height increased with age only at L4 and L5. Slope and
      caudal radius of curvature decreased with age, and increasingly convex morphology
      was noted at most levels. CONCLUSIONS: This large cadaveric study provides level
      specific morphometric data regarding the osseous dimensions of lumbar SPs
      relevant to techniques and devices targeting the lumbar SPs or the interspinous
      space. Of particular importance is the recognition that L5 has relatively
      different morphology when compared with more cranial levels. Potentially
      important differences were noted comparing women with men, black with white, and
      aging populations.

PMID- 25777740
TI  - Central nervous system penetration of antiretroviral drugs: pharmacokinetic,
      pharmacodynamic and pharmacogenomic considerations.
AB  - The prevalence of HIV-associated neurocognitive disorder (HAND) is increasing
      despite the widespread use of combination antiretroviral therapy (ART). Initial
      reports suggest that the use of antiretrovirals with good central nervous system
      (CNS) penetration leads to better neurocognitive outcomes, but this has not yet
      been confirmed in a large cohort study or randomised controlled trial. There is
      emerging evidence that high CNS concentrations of some antiretrovirals are
      potentially neurotoxic and may be associated with the development of HAND.
      Antiretroviral CNS exposure is ideally determined by determining the ratio of
      cerebrospinal fluid (CSF):plasma area under the curve of unbound drug, but
      usually only total drug concentrations are measured and the ratio of CSF:plasma
      drug concentration is done at a single time point, which can result in
      misclassifying CNS penetration ability. Efavirenz was previously thought to have
      poor CNS penetration, measured by the CSF:plasma ratio (0.87%), but when unbound
      concentrations were measured it was found to have good CNS penetration (85%).
      Indinavir and efavirenz are the only antiretroviral drugs for which CNS area
      under the concentration-time curves using unbound plasma and CSF concentrations
      has been calculated. Patient data to support the contribution of blood-brain
      barrier transporter polymorphisms to CNS antiretroviral concentrations are
      currently limited and lack power to detect true associations. Correlations
      between CNS antiretroviral exposure and effect is multifaceted, and to accurately
      predict CNS effects there is a need to develop a sophisticated intra-brain
      pharmacokinetic-pharmacodynamic-pharmacogenetic model that includes transporters
      as well as the influence of HIV.

PMID- 25777744
TI  - A case of myelopathy because of enchondromas from Maffucci syndrome with
      successful surgical treatment.
AB  - BACKGROUND CONTEXT: Maffucci syndrome is a rare disorder comprising multiple
      enchondromas associated with multiple hemangiomas. Less than 200 cases have been
      reported in the literature. Most reported cases comprised lesions of the long
      bone metaphyses, hands, and feet. No previous case of myelopathy due to
      enchondroma from Maffucci syndrome has been reported. PURPOSE: To highlight an
      interesting and rare presentation of thoracic myelopathy because of enchondromas
      from Maffucci syndrome. STUDY DESIGN: This is a case report of a single patient
      presenting with myelopathy in whom enchondromas from Maffucci syndrome were
      removed from the spinal canal with the return of normal function. METHODS:
      Clinical examination, magnetic resonance imaging, surgical resection, and
      histologic analysis. RESULTS: The patient experiencing myelopathy symptoms
      underwent a surgical resection of the offending lesions that resulted in return
      to normal function. CONCLUSIONS: Maffucci syndrome is a rare condition; however,
      in affected patients the possibility of structural spinal abnormalities causing
      cord compression must be considered, as discrete surgical resection can result in
      a good outcome.

PMID- 25777743
TI  - Improved patient selection by stratified surgical intervention: Aarhus Spinal
      Metastases Algorithm.
AB  - BACKGROUND CONTEXT: Choosing the best surgical treatment for patients with spinal
      metastases remains a significant challenge for spine surgeons. There is currently
      no gold standard for surgical treatments. The Aarhus Spinal Metastases Algorithm
      (ASMA) was established to help surgeons choose the most appropriate surgical
      intervention for patients with spinal metastases. PURPOSE: The purpose of this
      study was to evaluate the clinical outcome of stratified surgical interventions
      based on the ASMA, which combines life expectancy and the anatomical
      classification of patients with spinal metastases to inform surgical decision
      making. STUDY DESIGN/SETTING: This is a retrospective study based on a
      prospective database. PATIENT SAMPLE: A consecutive series of 515 spinal
      metastatic patients who underwent surgically treatment from December 1992 to June
      2012 in Aarhus University Hospital were included prospectively and analyzed in
      detail retrospectively. OUTCOME MEASURES: Survival time after surgery was
      determined for all patients. Neurological function was assessed using the Frankel
      score preoperatively and postoperatively (at the time of discharge). Complete
      outcome data were retrieved in 97.5% of this cohort. METHODS: Patients with
      spinal metastases were identified from an institutional database that
      prospectively collected data since 1992. Survival status data were obtained from
      a national registry. Neurological function was determined from the same
      institutional database or local Electronic Patient Journal system. Surgeons
      evaluated and classified patients into five surgical groups preoperatively by
      using the revised Tokuhashi score (TS) and the Tomita anatomical classification
      (TC). RESULTS: The overall median survival time of the cohort was 6.8 (95%
      confidence interval: 6.1-7.9) months. The median survival times in the five
      surgical groups determined by the ASMA were 2.1 (TS 0-4, TC 1-7), 5.1 (TS 5-8, TC
      1-7), 12.1 (TS 9-11, TC 1-7 or TS 12-15, TC 7), 26.0 (TS 12-15, TC 4-6), and 36.0
      (TS 12-15, TC 1-3) months. The 30-day mortality rate was 7.5%. Postoperative
      neurological function was maintained or improved in 469 patients (92.3%). Overall
      reoperation rate was 13.5%, commonly because of postoperative hematoma and new
      limb weakness. CONCLUSIONS: The ASMA recommends at least two surgical options for
      a particular patient by determining the preoperative life expectancy and
      anatomical classification of the spinal metastases. This algorithm could help
      spine surgeons to discriminate the risks of surgeries. The ASMA provides a tool
      to guild surgeons to evaluate the spinal metastases patients, select potential
      optimal surgery, and avoid life-threatening risks.

PMID- 25777747
TI  - Overexpression of COX-2 but not indoleamine 2,3-dioxygenase-1 enhances the
      immunosuppressive ability of human umbilical cord-derived mesenchymal stem cells.
AB  - Owing to their immunosuppressive properties mesenchymal stem cells (MSCs) are
      widely applicable in the treatment of autoimmune disease. The aim of this study
      was to investigate whether the indoleamine 2,3-dioxygenase-1 (IDO-1) and
      cyclooxygenase-2 (COX-2) genes enhanced the immunosuppressive functional ability
      of MSCs following stable transfection. To strengthen the immunomodulatory ability
      of MSCs, IDO-1 and COX-2 were overexpressed in umbilical cord progenitor cell
      derived MSCs using recombinant plasmids and electroporation. RT-qPCR analysis and
      western blotting confirmed the expression of IDO-1 and COX-2 in transfected MSCs.
      Further functional assays in co-culture experiments, including lymphocyte
      proliferation and cyto-toxicity assays showed that COX-2-transfected MSCs
      possessed more potent immunomodulatory cells than the untreated MSCs, or MSCs
      transfected with IDO-1. Additionally, synthesis of interferon-gamma and tumor
      necrosis factor-alpha (TNF-alpha) was significantly inhibited in lymphocytes co
      cultured with COX-2-transfected MSCs, which was consistent with changes in immune
      related genes in MSCs. An enhanced expression of IDO-1, COX-2, heme-oxygenase-1,
      inducible nitric-oxide synthase, TNF-alpha-stimulated gene/protein-6,
      transforming growth factor-beta (TGF-beta), human leukocyte antigen molecule 5
      (HLA-G5) and interleukin-10 (IL-10) was identified following COX-2 transfection.
      We showed that the overexpression of COX-2 enhanced the immunosuppressive
      function of MSCs. COX-2-modified MSCs more potently inhibited the activation and
      proliferation of peripheral blood mononuclear cells.

PMID- 25777748
TI  - Multiple roles of graphene in heterogeneous catalysis.
AB  - Scientific interest in graphene as a catalyst and as a catalyst support in
      heterogeneous catalytic reactions has grown dramatically over the past several
      years. The present critical review summarizes the multiple roles of graphene in
      heterogeneous catalysis and highlights the influence of defects, heteroatom
      containing functionalities, and graphene's two-dimensional structure on catalytic
      performance. We first discuss the role and advantages of graphene as a catalyst
      support, with emphasis on its interactions with the catalytic phases and the
      influence of mass transfer processes. We then clarify the origin of the intrinsic
      catalytic activity of graphene in heterogeneous catalytic reactions. Finally we
      suggest challenges and potential practical applications for graphene in
      industrial processes. 

PMID- 25777746
TI  - Explaining the frequency of alcohol consumption in a conflict zone: Jews and
      Palestinians in Israel.
AB  - Experiencing stress and exposure to terrorism may have an adverse effect on
      health risk behaviors. Few studies have examined alcohol use among adults living
      in Israel under chronic, stressful terrorism-related conditions. In this study,
      we examined the relationships of demographics, past stressful events, and
      terrorism exposure to the frequency of alcohol use and the mediating roles of
      depressive and post-traumatic stress disorder (PTSD) symptoms. We used three
      waves of data from a 2007-2008 nationally representative sample of Jewish and
      Palestinian adults in Israel. We assessed past stressful events, in addition to
      direct and indirect exposures to terrorism. Results indicated that past stressful
      events and exposure to terrorism were not directly associated with alcohol use,
      but were indirectly associated and mediated by depressive and PTSD symptomology.
      Mental health symptoms were differentially associated with alcohol use. More
      frequent drinking was mediated by higher levels of depression, including for
      women and Palestinians; however, PTSD symptom severity was related to less
      frequent drinking. Mental health may play a prominent role in the frequency of
      alcohol use among adults exposed to terrorism in Israel. Alcohol use, as a coping
      mechanism, may differ by demographic characteristics (gender and ethnicity) and
      psychological symptomology for adults living in a conflict zone in Israel. 

PMID- 25777745
TI  - Recent advances in the genetics of systemic sclerosis: toward biological and
      clinical significance.
AB  - Significant advances have been made in understanding the genetic basis of
      systemic sclerosis (SSc) in recent years. Genomewide association and other large
      scale genetic studies have identified 30 largely immunity-related genes which are
      significantly associated with SSc. We review these studies, along with genomewide
      expression studies, proteomic studies, genetic mouse models, and insights from
      rare sclerodermatous diseases. Collectively, these studies have begun to identify
      pathways that are relevant to SSc pathogenesis. The findings presented in this
      review illustrate how both genetic and genomic aberrations play important roles
      in the development of SSc. However, despite these recent discoveries, there
      remain major gaps between current knowledge of SSc, a unified understanding of
      pathogenesis, and effective treatment. To this aim, we address the important
      issue of SSc heterogeneity and discuss how future research needs to address this
      in order to develop a clearer understanding of this devastating and complex
      disease. 

PMID- 25777749
TI  - Endoscopic evaluation of food bolus formation and its relationship with the
      number of chewing cycles.
AB  - It is known that solid food is transported to the pharynx actively in parallel to
      it being crushed by chewing and mixed with saliva in the oral cavity. Therefore,
      food bolus formation should be considered to take place from the oral cavity to
      the pharynx. In previous studies, the chewed food was evaluated after the food
      had been removed from the oral cavity. However, it has been pointed out that
      spitting food out of the oral cavity interferes with natural food bolus
      formation. Therefore, we observed food boluses immediately before swallowing
      using an endoscope to establish a method to evaluate the food bolus-forming
      function, and simultaneously performed endoscopic evaluation of food bolus
      formation and its relationship with the number of chewing cycles. The subject was
      inserted the endoscope nasally and instructed to eat two coloured samples of
      boiled rice simultaneously in two ingestion conditions ('as usual' and 'chewing
      well'). The condition of the food bolus was graded into three categories for each
      item of grinding, mixing and aggregation and scored 2, 1 and 0. The score of
      aggregation was high under both ingestion conditions. The scores of grinding and
      mixing tended to be higher in subjects with a high number of chewing cycles, and
      the score of aggregation was high regardless of the number of chewing cycles. It
      was suggested that food has to be aggregated, even though the number of chewing
      cycles is low and the food is not ground or mixed for a food bolus to reach the
      swallowing threshold. 

PMID- 25777750
TI  - Communication at an online infertility expert forum: provider responses to
      patients' emotional and informational cues.
AB  - Online patient-provider communication has become increasingly popular in
      fertility care. However, it is not known to what extent patients express cues or
      concerns and how providers respond. In this study, we investigated cues and
      responses that occur in online patient-provider communication at an infertility
      specific expert forum. We extracted 106 threads from the multidisciplinary expert
      forum of two Dutch IVF clinics. We performed the following analyses: (1) thematic
      analysis of patients' questions; and (2) rating patients' emotional and
      informational cues and subsequent professionals' responses using an adaptation of
      the validated Medical Interview Aural Rating Scale. Frequencies of themes,
      frequencies of cues and responses, and sequences (what cue is followed by what
      response) were extracted. Sixty-five infertile patients and 19 providers
      participated. The most common themes included medication and lifestyle. Patients
      gave more informational than emotional cues (106 versus 64). Responses to
      informational cues were mostly adequate (61%). The most common response to
      emotional cues was empathic acknowledgment (72%). Results indicate that an online
      expert forum could have a positive effect on patient outcomes, which should guide
      future research. Offering infertile patients an expert forum to communicate with
      providers can be a promising supplement to usual care in both providing
      information and addressing patients' concerns. 

PMID- 25777751
TI  - Animal models of lupus and lupus nephritis.
AB  - This article reviews the commonly used murine strains for studying lupus and
      lupus nephritis, including strains that develop lupus spontaneously, congenic
      strains, induced models of lupus, as well as genetically engineered mouse models
      of lupus bearing transgenes or knockouts. The review then summarizes the main
      cellular and molecular pathways that lead to the pathogenesis of this autoimmune
      disease, including autoantibodies. Finally, it concludes with therapeutic
      insights gained from using mouse models of lupus. To sum, much of what we have
      learned about lupus has arisen from studying mouse models of the disease, and the
      laboratory mouse continues to be one of the best tools for studying human SLE. 

PMID- 25777753
TI  - Animal models of systemic sclerosis.
AB  - Systemic sclerosis is a systemic connective tissue disorder characterized by the
      fibrosis of the skin and certain visceral organs, vasculopathy, and immunological
      abnormalities. Several genetic and inducible animal models of SSc have been
      developed and are available for research studies. The purpose of this review is
      to summarize the various animal models of systemic sclerosis and describe the
      various contributions of these models in terms of understanding the
      pathophysiology of the condition and searching for new therapeutic strategies for
      this incurable disease. 

PMID- 25777754
TI  - Mouse models of anti-neutrophil cytoplasmic antibody-associated vasculitis.
AB  - Inflammation of blood vessels (vasculitis) results from many pathological
      processes and is found in many different diseases. However, in most situations,
      the pathological processes inducing vasculitis are unknown. The discovery of anti
      neutrophil cytoplasmic autoantibodies (ANCAs) in the 1980s opened the door for
      studies that eventually led to the description of a new previously undescribed
      disease, ANCA-associated vasculitis (AAV). Unravelling the immunopathogenesis of
      this new disease resulted largely from the development of animal models. The
      major breakthroughs were the description of ANCA, its association with small
      vessel vasculitis and the discovery of its target autoantigens (myeloperoxidase
      and Proteinase 3). Three major disease syndromes comprise the AAVs, microscopic
      polyangiitis, granulomatosis with polyangiitis and eosinophilic granulomatosis
      with polyangiitis (EGPA). Recent human studies suggest that proteinase 3 and
      myeloperoxidase associated vasculitis are two separate but related diseases. The
      ability to induce murine autoimmunity to myeloperoxidase including ANCA (with the
      same immune staining patterns as human ANCA) and the capacity of this anti
      myeloperoxidase autoimmunity to induce disease with many of the characteristic
      features of human AAV are well developed. However, the development of animal
      models of anti-proteinase 3 ANCA and EGPA is much less well developed. Animal
      models are important in understanding the human disease and in particular in
      defining potential therapeutic targets and in early stage therapeutic testing of
      potential drugs. Clearly the relevance of animal models depends on how closely
      they mimic human diseases. The current status of animal models of vasculitis will
      be described in detail with reference to these criteria. 

PMID- 25777755
TI  - An Update on Animal Models of Autoimmune Hepatitis: Are we There Yet?
AB  - Autoimmune hepatitis is characterized by a progressive destruction of the liver
      parenchyma and a chronic fibrosis. Although the major targets of this autoimmune
      mediated disease have been identified more than two decades ago, the current
      treatment of autoimmune hepatitis is still based on traditional therapies
      including a glucocorticoid treatment. One reason for this impasse is the limited
      availability of reliable animal models that reflect the clinical features of
      autoimmune hepatitis and allow for the identification of critical factors driving
      the autoimmune destruction and the evaluation of innovative therapies. However,
      the status of the liver as an immune privileged organ harbouring many
      immunosuppressing mechanisms hampers the development of such models. Here we will
      review the past and present attempts to develop a consistent animal model for
      autoimmune hepatitis. 

PMID- 25777756
TI  - Mouse models of primary biliary cirrhosis.
AB  - Primary biliary cirrhosis (PBC) is a chronic and progressive cholestatic liver
      disease of unknown etiopathogenesis that mainly affects middle-aged women.
      Patients show non-suppurative cholangitis with damage and destruction of small-
      and medium-sized intrahepatic bile ducts. Characteristically, the disease is
      strongly associated with autoimmune phenomena such as the appearance of serum
      antimitochondrial autoantibodies (AMA) and portal infiltrates with autoreactive T
      cells which recognize the inner lipoyl domain of the E2 component of the pyruvate
      dehydrogenase complex (PDC-E2). Here we review the major characteristics of a
      series of inducible and genetically modified animal models of PBC and analyze
      their similarities and differences with PBC features in humans. 

PMID- 25777752
TI  - Mouse Models of Primary Sjogren's Syndrome.
AB  - Sjogren's syndrome (SjS) is a chronic autoimmune disorder characterized by immune
      cell infiltration and progressive injury to the salivary and lacrimal glands. As
      a consequence, patients with SjS develop xerostomia (dry mouth) and
      keratoconjunctivitis sicca (dry eyes). SjS is the third most common rheumatic
      autoimmune disorder, affecting 4 million Americans with over 90% of patients
      being female. Current diagnostic criteria for SjS frequently utilize histological
      examinations of minor salivary glands for immune cell foci, serology for
      autoantibodies, and dry eye evaluation by corneal or conjunctival staining. SjS
      can be classified as primary or secondary SjS, depending on whether it occurs
      alone or in association with other systemic rheumatic conditions, respectively.
      Clinical manifestations typically become apparent when the disease is relatively
      advanced in SjS patients, which poses a challenge for early diagnosis and
      treatment of SjS. Therefore, SjS mouse models, because of their close resemblance
      to the human SjS, have been extremely valuable to identify early disease markers
      and to investigate underlying biological and immunological dysregulations.
      However, it is important to bear in mind that no single mouse model has
      duplicated all aspects of SjS pathogenesis and clinical features, mainly due to
      the multifactorial etiology of SjS that includes numerous susceptibility genes
      and environmental factors. As such, various mouse models have been developed in
      the field to try to recapitulate SjS. In this review, we focus on recent mouse
      models of primary SjS xerostomia and describe them under three categories of
      spontaneous, genetically engineered, and experimentally induced models. In
      addition, we discuss future perspectives highlighting pros and cons of utilizing
      mouse models and current demands for improved models. 

PMID- 25777757
TI  - Preclinical models of Graves' disease and associated secondary complications.
AB  - Autoimmune thyroid disease is the most common organ-specific autoimmune disorder
      which consists of two opposing clinical syndromes, Hashimoto's thyroiditis and
      Graves' (hyperthyroidism) disease. Graves' disease is characterized by goiter,
      hyperthyroidism, and the orbital complication known as Graves' orbitopathy (GO),
      or thyroid eye disease. The hyperthyroidism in Graves' disease is caused by
      stimulation of function of thyrotropin hormone receptor (TSHR), resulting from
      the production of agonist antibodies to the receptor. A variety of induced mouse
      models of Graves' disease have been developed over the past two decades, with
      some reproducible models leading to high disease incidence of autoimmune
      hyperthyroidism. However, none of the models show any signs of the orbital
      manifestation of GO. We have recently developed an experimental mouse model of GO
      induced by immunization of the plasmid encoded ligand binding domain of human
      TSHR cDNA by close field electroporation that recapitulates the orbital pathology
      in GO. As in human GO patients, immune mice with hyperthyroid or hypothyroid
      disease induced by anti-TSHR antibodies exhibited orbital pathology and chemosis,
      characterized by inflammation of orbital muscles and extensive adipogenesis
      leading to expansion of the orbital retrobulbar space. Magnetic resonance imaging
      of the head region in immune mice showed a significant expansion of the orbital
      space, concurrent with proptosis. This review discusses the different strategies
      for developing mouse models in Graves' disease, with a particular focus on GO.
      Furthermore, it outlines how this new model will facilitate molecular
      investigations into pathophysiology of the orbital disease and evaluation of new
      therapeutic interventions. 

PMID- 25777758
TI  - Animal models to investigate pathomechanisms and evaluate novel treatments for
      autoimmune bullous dermatoses.
AB  - Autoimmune bullous dermatoses (AIBD), such as pemphigus, bullous pemphigoid or
      epidermolysis bullosa acquisita, are prototypical organ-specific autoimmune
      diseases. Clinically they are characterized by widespread mucocutaneous
      blistering, which is often difficult to treat. Patients with AIBD suffer from a
      significant morbidity and an increased mortality. In AIBD blistering is caused by
      autoantibodies targeting structural proteins of the skin. During the past decades
      animal models of AIBD have been developed. These animal models have greatly
      contributed to our current understanding of AIBD pathogenesis. Most of these
      insights, however, still await their translation into clinical use. Recently,
      AIBD animal models have been used to test the efficacy of known and novel drugs.
      Hence, these models are now not only employed to unravel the pathogenesis of
      AIBD, but also to assess therapeutic approaches to address the so far unmet high
      medical need for new treatments. We here review animal model of AIBD: In addition
      to spontaneously arising AIBD in animals, AIBD can be induced, mostly in mice, by
      (i) transfer of (auto)-antibodies, (ii) transfer of (auto)-antigen specific
      lymphocytes, (iii) immunization or (iv) by genetic modifications leading to
      spontaneous blistering. In combined use, these models allow dissecting all
      aspects of AIBD pathogenesis, i.e. loss of tolerance, autoantibody production and
      blistering. Overall we aim to foster a broader use of AIBD animal models,
      especially in translational biomedical research, to deepen our understanding of
      AIBD pathogenesis and to develop novel treatments for patients.

PMID- 25777759
TI  - Mouse models of multiple sclerosis: lost in translation?
AB  - Multiple sclerosis (MS) is a chronic neurological disorder of the central nervous
      system (CNS) leading to progressive accumulation of neurological deficits arising
      from recurrent episodes of inflammation, demyelination and neuronal degeneration.
      While the aetiology of the disease is unknown MS is widely considered to be the
      result of aberrant T cell and antibody responses to CNS antigens giving rise to
      the common concept that MS is an autoimmune disease or that there is an
      autoimmune component in the pathogenesis. This idea has lead to the development
      of experimental autoimmune encephalomyelitis (EAE) mouse models of MS in which
      immunisation with CNS antigens induces neurological and pathological signs of
      disease in mice. In addition to EAE models, injection with neurotropic viruses
      has been used to examine how infections are implicated in the disease process and
      how they may generate autoimmune responses in the CNS. Viral models are also
      crucial to investigate the impact of blocking trafficking of immune responses
      into the CNS since an emerging side-effect of current immunotherapeutic
      approaches in MS is the reactivation of viruses within the CNS. To investigate
      myelin damage and repair in the absence of the adaptive immune response, toxin
      induced demyelination using cuprizone, ethidium bromide and lysolecithin, which
      rapidly leads to remyelination when the toxins are withdrawn, is also reviewed.
      Mice also lend themselves to the vast array of transgenic technologies to probe
      specific pathways as well as the use of humanised transgenic mice to examine the
      impact of human molecules. Despite the vast array of mouse models EAE is the most
      frequently exploited paradigm used to develop therapeutic approaches. However,
      despite over one thousand compounds used in the treatment of EAE few have become
      licenced for treatment of MS so far. Thus, this review also debates the reasons
      for these failures in mouse models as well as discusses how mouse models can be
      better utilised to provide more powerful preclinical tools to develop rational
      therapies for multiple sclerosis. 

PMID- 25777760
TI  - Mouse models of autoimmune uveitis.
AB  - Uveitis is a sight threatening intraocular inflammation accounting for
      approximately 10% of blindness worldwide. On the basis of aetiology, disease can
      be classified as infectious or non-infectious; and by anatomical localization of
      inflammation as anterior, posterior and panuveitis. Non-infectious uveitis is
      believed to be autoimmune in nature with Th1 and Th17 cells being identified as
      the prominent effector cell types. Numerous animal models of autoimmune uveitis
      were developed contributing to our understanding of this inflammatory condition.
      The classical peptide-induced experimental autoimmune uveoretinitis (EAU) model
      resembles human posterior uveitis due to the recurrent/relapsing nature of the
      disease; while the intraocular inflammation triggered by administration of
      bacterial lipopolisaccharide (endotoxin-induced uveitis, EIU) mimics closely
      anterior uveitis. The clinical need for novel, more targeted forms of anti
      inflammatory therapy has emerged as currently available therapeutic strategies
      are associated with a number of adverse effects and intolerance in patients. This
      review summarises knowledge about existing mouse models of uveitis, discusses
      mechanisms driving intraocular inflammation and describes possible customised
      translational treatment strategies that can be potentially used in the clinic to
      prevent blindness in patients.

PMID- 25777761
TI  - Mouse models of myasthenia gravis.
AB  - Myasthenia gravis is a muscle weakness disease characterized by autoantibodies
      that target components of the neuromuscular junction, impairing synaptic
      transmission. The most common form of myasthenia gravis involves antibodies that
      bind the nicotinic acetylcholine receptors in the postsynaptic membrane. Many of
      the remaining cases are due to antibodies against muscle specific tyrosine kinase
      (MuSK). Recently, autoantibodies against LRP4 (another component of the MuSK
      signaling complex in the postsynaptic membrane) were identified as the likely
      cause of myasthenia gravis in some patients. Fatiguing weakness is the common
      symptom in all forms of myasthenia gravis, but muscles of the body are
      differentially affected, for reasons that are not fully understood. Much of what
      we have learnt about the immunological and neurobiological aspects of the
      pathogenesis derives from mouse models. The most widely used mouse models involve
      either passive transfer of autoantibodies, or active immunization of the mouse
      with acetylcholine receptors or MuSK protein. These models can provide a robust
      replication of many of the features of the human disease. Depending upon the
      protocol, acute fatiguing weakness develops 2 - 14 days after the start of
      autoantibody injections (passive transfer) or might require repeated
      immunizations over several weeks (active models). Here we review mouse models of
      myasthenia gravis, including what they have contributed to current understanding
      of the pathogenic mechanisms and their current application to the testing of
      therapeutics. 

PMID- 25777762
TI  - Mouse models of autoimmune diseases: immune thrombocytopenia.
AB  - Immune thrombocytopenia or ITP is a debilitating and life-threatening disorder
      affecting more than 4 in every 10, 000 adults annually. Following a basic
      understanding of the immunopathology underlying ITP, namely that production of
      anti-platelet antibodies results in accelerated platelet clearance and
      thrombocytopenia, animal models of ITP were quickly developed. Rodent models that
      develop ITP spontaneously or by passive transfer of anti-platelet sera or
      antibodies have become instrumental in investigating the mechanisms responsible
      for the breakdown of tolerance in human ITP, understanding the immunopathology
      that underlies the progression of platelet destruction, elucidating the
      mechanism(s) of therapeutic amelioration of the ITP, and driving the development
      of new therapeutic modalities. This review aims to capture the development
      history and methodology of currently available ITP disease models, and review
      their advantages and limitations in the study of various aspects of ITP. We also
      review how closely the various ITP models reflect the pathobiology of human ITP
      and their usefulness in advancing the development of new therapeutics, which are
      particularly needed to address the unmet need of patients who are refractory to
      the currently available repertoire of interventions. 

PMID- 25777763
TI  - Mouse models of autoimmune diseases - autoimmune myocarditis.
AB  - Cardiovascular diseases are the leading cause of death in industrialized nations
      worldwide. Of all deaths resulting from cardiovascular diseases, 2% are caused by
      inflammatory heart disease; specifically, myocarditis. The etiology causing
      myocarditis still remains unclear. Both infectious and non-infectious factors are
      capable of triggering myocarditis. Acute myocarditis manifests itself in a
      variety of ways ranging from subclinical disease to sudden heart failure, as well
      as the occurrence of chest pain, palpitations, and syncope. Myocarditis can lead
      to dilated cardiomyopathy, this being the most frequent cause for heart
      transplantation. Since the underlying mechanism and the pathways behind the
      disease initiation and progression still need to be elucidated, the need for
      mouse models simulating the human disease is evident. Various mouse models are
      frequently used to study myocarditis. Inflammation of the myocardium as a result
      of infectious agents can be investigated with a widely used animal model where
      mice are infected with coxsackievirus B3. For autoimmune (non-viral) myocarditis,
      several mouse models (including induction with myosin or troponin I) have been
      established to better understand the role of autoantibodies and their influence
      on disease progression. With these different models, various phases of the
      disease can be investigated and these findings are used to develop more specific
      therapies that can be translated into the clinic as a "bench-to-bedside"
      approach. 

PMID- 25777764
TI  - History and milestones of mouse models of autoimmune diseases.
AB  - Autoimmune diseases are a group of disorders mediated by self-reactive T cells
      and/or autoantibodies. Mice, as the most widely used animal for modeling
      autoimmune disorders, have been extensively used in the investigation of disease
      pathogenesis as well as in the search for novel therapeutics. Since the first
      mouse model of multiple sclerosis was established more than 60 years ago,
      hundreds of mouse models have been established for tens of autoimmune diseases.
      These mouse models can be divided into three categories based on the approaches
      used for disease induction. The first one represents the induced models in which
      autoimmunity is initiated in mice by immunization, adoptive transfer or
      environmental factors. The second group is formed by the spontaneous models where
      mice develop autoimmune disorders without further induction. The third group
      refers to the humanized models in which mice bearing humanized cells, tissues, or
      genes, develop autoimmune diseases either spontaneously or by induction. This
      article reviews the history and highlights the milestones of the mouse models of
      autoimmune diseases. 

PMID- 25777765
TI  - Nitrogen permease regulator-like 2 enhances sensitivity to oxaliplatin in colon
      cancer cells.
AB  - Colorectal cancer (CRC) is the third most common cancer worldwide.
      Chemotherapeutic compounds used for the treatment of CRC include oxaliplatin (L
      OHP). While L-OHP improves CRC survival, certain patients are resistant. The
      nitrogen permease regulator like-2 (NPRL2) gene is a candidate tumor suppressor
      gene that resides in a 120-kb homozygous deletion region on chromosome 3p21.3. In
      the present study, it was demonstrated that NPRL2 overexpression increases the
      sensitivity of HCT116 cells to L-OHP. The IC50 of L-OHP was decreased in cells
      transduced with NPRL2 compared with negative control (NC) cells and the effect of
      NPRL2 on L-OHP sensitivity was time dependent. Following NPRL2 transduction in
      HCT116 cells, the cell cycle was arrested in the G1 phase and a partial decrease
      in the S phase population was observed. Flow cytometric analysis revealed that
      NPRL2 transduction and L-OHP treatment increased apoptosis compared with NC
      cells. The mechanism through which NPRL2 overexpression enhances L-OHP
      sensitivity involves downregulation of the functions of the phosphatidylinositol
      3-kinase/Akt/mammalian target of rapamycin network. Furthermore, L-OHP
      upregulated caspase-3 and caspase-9 to promote apoptosis in NPRL2-overexpressing
      cells compared with cells that were transduced with NPRL2 or treated with L-OHP
      and NC cells (P<0.01). NPRL2 overexpression led to the downregulation of CD24,
      which could significantly reduce tumor invasiveness and decrease the metastatic
      capacity of HCT116 cells. These mechanisms are likely active in other types of
      cancer and may be exploited for the development of novel cancer therapies.

PMID- 25777766
TI  - Zeroing in on cereblon.

PMID- 25777767
TI  - Atomic picture of elastic deformation in a metallic glass.
AB  - The tensile behavior of a Ni60Nb40 metallic glass (MG) has been studied by using
      ab initio density functional theory (DFT) calculation with a large cell
      containing 1024 atoms (614 Ni and 410 Nb). We provide insight into how a super
      elastic limit can be achieved in a MG. Spatially inhomogeneous responses of
      single atoms and also major polyhedra are found to change greatly with increasing
      external stress when the strain is over 2%, causing the intrinsically
      viscoelastic behavior. We uncover the origin of the observed super elastic strain
      limit under tension (including linear and viscoelastic strains) in small-sized MG
      samples, mainly caused by inhomogeneous distribution of excess volumes in the
      form of newly formed subatomic cavities.

PMID- 25777768
TI  - Quantum dots: bright and versatile in vitro and in vivo fluorescence imaging
      biosensors.
AB  - Semiconductor quantum dots (QDs) have become important fluorescent probes for in
      vitro and in vivo bioimaging research. Their nanoparticle surfaces for versatile
      bioconjugation, their adaptable photophysical properties for multiplexed
      detection, and their superior stability for longer investigation times are the
      main advantages of QDs compared to other fluorescence imaging agents. Here, we
      review the recent literature dealing with the design and application of QD
      bioconjugates for advanced in vitro and in vivo imaging. After a short summary of
      QD preparation and their most important properties, different QD-based imaging
      applications will be discussed from the technological and the biological point of
      view, ranging from super-resolution microscopy and single-particle tracking over
      in vitro cell and tissue imaging to in vivo investigations. A substantial part of
      the review will focus on multifunctional applications, in which the QD
      fluorescence is combined with drug or gene delivery towards theranostic
      approaches or with complementary technologies for multimodal imaging. We also
      briefly discuss QD toxicity issues and give a short outlook on future directions
      of QD-based bioimaging. 

PMID- 25777769
TI  - A linker strategy for the production and crystallization of Toll/interleukin-1
      receptor/resistance protein domain complexes.
AB  - Structural characterization of protein-protein complexes is required to fully
      understand biological processes. However, such studies can be difficult,
      particularly when the interactions are transient. In some cases, the covalent
      linking of weakly interacting binding partners has been shown to facilitate
      structural studies. Here, we used this approach to investigate, by X-ray
      crystallography, the interactions between TIR (Toll/interleukin-1
      receptor/resistance protein) domains from proteins involved in plant and animal
      innate immunity. Combinations of TIR domains known to interact were covalently
      attached using short glycine- and serine-rich linkers. This approach enabled the
      production of a number of TIR-TIR domain complexes in soluble form, facilitating
      crystallization studies. Crystallization of two of the tested combinations was
      achieved. Furthermore, production in soluble form was achieved for another two
      combinations, where this was not possible for individual proteins. Our results
      demonstrate that the linker strategy can aid in the structural studies of TIR
      domains. Similarly, this approach has potential for improving protein production
      and facilitating structural studies of other protein-protein interaction domains.

PMID- 25777770
TI  - A novel dual ex vivo lung perfusion technique improves immediate outcomes in an
      experimental model of lung transplantation.
AB  - The lungs are dually perfused by the pulmonary artery and the bronchial arteries.
      This study aimed to test the feasibility of dual-perfusion techniques with the
      bronchial artery circulation and pulmonary artery circulation synchronously
      perfused using ex vivo lung perfusion (EVLP) and evaluate the effects of dual
      perfusion on posttransplant lung graft function. Using rat heart-lung blocks, we
      developed a dual-perfusion EVLP circuit (dual-EVLP), and compared cellular
      metabolism, expression of inflammatory mediators, and posttransplant graft
      function in lung allografts maintained with dual-EVLP, standard-EVLP, or cold
      static preservation. The microvasculature in lung grafts after transplant was
      objectively evaluated using microcomputed tomography angiography. Lung grafts
      subjected to dual-EVLP exhibited significantly better lung graft function with
      reduced proinflammatory profiles and more mitochondrial biogenesis, leading to
      better posttransplant function and compliance, as compared with standard-EVLP or
      static cold preservation. Interestingly, lung grafts maintained on dual-EVLP
      exhibited remarkably increased microvasculature and perfusion as compared with
      lungs maintained on standard-EVLP. Our results suggest that lung grafts can be
      perfused and preserved using dual-perfusion EVLP techniques that contribute to
      better graft function by reducing proinflammatory profiles and activating
      mitochondrial respiration. Dual-EVLP also yields better posttransplant graft
      function through increased microvasculature and better perfusion of the lung
      grafts after transplantation. 

PMID- 25777771
TI  - Comparison between single- and multi-sensor oesophageal temperature probes during
      atrial fibrillation ablation: thermodynamic characteristics.
AB  - AIMS: Oesophageal temperature monitoring with single-sensor probe (SSP) has a
      variable ability to predict oesophageal ulceration as a consequence of pulmonary
      vein isolation (PVI). Multi-sensor self-expandable probes (MSPs) may offer
      improved thermal monitoring. The objective of this study was to compare the
      thermodynamic characteristics of both probes during PVI. METHODS AND RESULTS:
      This prospective study enrolled 20 patients undergoing index PVI. Ten patients
      (group A) underwent dual monitoring with SSP and MSP and 10 control patients
      (group B) were monitored with SSP alone. Time to initial rise (>0.2 degrees C),
      time to 1.0 degrees C rise, peak temperature, and decay were recorded with each
      posterior wall lesion (20 W, 198 applications). The operator was blinded to the
      MSP temperature data and ablation was only interrupted when SSP temperature
      increased by >=2 degrees C. All patients underwent endoscopy within 24 h. Initial
      temperature increase was detected earlier with MSP (13.4 +/- 7.5 vs. 30.5 +/-
      15.4 s; P < 0.001); led to shorter time to 1.0 degrees C rise (18.5 +/- 10.1 vs.
      32.1 +/- 12.0 s; P < 0.001); and higher change in peak temperature (1.6 +/- 2.0
      vs. 0.60 +/- 0.53 degrees C; P < 0.001). Decay time was similar between the
      probes (146.1 +/- 35.3 vs. 150.4 +/- 48.4 s; P = 0.89). The incidence of
      oesophageal ulceration was similar between the Groups A and B (5 and 4,
      respectively). Multi-sensor self-expandable probe provided greater sensitivity
      (100 vs. 60%) and similar specificity (60%) for detection of oesophageal
      ulceration. Five swine underwent oesophageal mapping before and after MSP
      placement without alteration in size or position. CONCLUSION: Multi-sensor probes
      provide a superior thermodynamic profile. Its clinical value in reducing
      oesophageal injury requires further evaluation.

PMID- 25777772
TI  - Pentagermapyramidane: crystallizing the "transition-state" structure.
AB  - The first example of the homonuclear pyramidanes, pentagermapyramidane, was
      synthesized, fully characterized, and computationally studied to reveal its
      peculiar structural features and the nature of its apex-to-base bonding
      interactions. Both solid-state and solution structures of pentagermapyramidane
      are discussed based on the computed stabilities of its square-pyramidal and
      distorted forms. 

PMID- 25777773
TI  - Sink property of metallic glass free surfaces.
AB  - When heated to a temperature close to glass transition temperature, metallic
      glasses (MGs) begin to crystallize. Under deformation or particle irradiation,
      crystallization occurs at even lower temperatures. Hence, phase instability
      represents an application limit for MGs. Here, we report that MG membranes of a
      few nanometers thickness exhibit properties different from their bulk MG
      counterparts. The study uses in situ transmission electron microscopy with
      concurrent heavy ion irradiation and annealing to observe crystallization
      behaviors of MGs. For relatively thick membranes, ion irradiations introduce
      excessive free volumes and thus induce nanocrystal formation at a temperature
      linearly decreasing with increasing ion fluences. For ultra-thin membranes,
      however, the critical temperature to initiate crystallization is about 100 K
      higher than the bulk glass transition temperature. Molecular dynamics simulations
      indicate that this effect is due to the sink property of the surfaces which can
      effectively remove excessive free volumes. These findings suggest that
      nanostructured MGs having a higher surface to volume ratio are expected to have
      higher crystallization resistance, which could pave new paths for materials
      applications in harsh environments requiring higher stabilities.

PMID- 25777774
TI  - Innovative medicines: new regulatory procedures for the third millennium.
AB  - Despite tremendous progress in science and increasing investment in research and
      development, patients' access to innovative medicines remains limited. This is in
      part due to increasing regulatory requirements for product authorisation and cost
      constrained national health systems. At the European Medicines Agency (EMA), we
      have tried to address these constraints by adapting our organisation and
      activities to changing business models, new technologies, and the current and
      emerging health needs in Europe. The main EMA initiatives to provide patients
      with effective, safe and affordable medicines are reviewed. 

PMID- 25777775
TI  - Carotenoids and fat-soluble vitamins in horse tissues: a comparison with cattle.
AB  - Carotenoids are important for human health because of their provitamin A function
      among other biological actions. Their implication on consumer point of view of
      cattle products have been widely studied, but very little information is
      available for horse products. The aim of this study was to study the accumulation
      of carotenoids, retinoids and tocopherol by HPLC and HPLC-MS analysis in
      different horse tissues (plasma, milk, adipose tissue and liver) and compare it
      with that of cattle. Fat color was also studied. Four groups of animals were
      studied (15 animals within each group): lactating mares (709.82+/-23.09 kg) and
      cows (576.93+/-31.94 kg) reared outdoors; and foals (556.8+/-25.9 kg, 14 months
      old) and calves (474.7+/-36.2 kg, 14 months old) reared indoors. Both mares and
      foals were from the Hispano-Breton breed, whereas both cows and calves belonged
      to the commercial crossbred Limousine-Retinta. Differences in plasma and milk
      carotenoids (P0.05). Both species showed different levels of accumulation of
      retinoids in the liver, with the foal having better accumulation (P<0.01,
      P<0.001). These results indicate that there are species-specific differences in
      the accumulation of carotenoids, retinol and tocopherol, but further studies are
      required to establish the mechanism of these differences. 

PMID- 25777776
TI  - Suppression of Autoimmunity and Renal Disease in Pristane-Induced Lupus by
      Myeloperoxidase.
AB  - OBJECTIVE: Myeloperoxidase (MPO) locally contributes to organ damage in various
      chronic inflammatory conditions by generating reactive intermediates. The
      contribution of MPO in the development of experimental lupus is unknown. The aim
      of this study was to define the role of MPO in murine lupus nephritis (LN).
      METHODS: LN was induced in C57BL/6 wild-type (WT) and MPO knockout (MPO(-/-) )
      mice by intraperitoneal injection of pristane. Autoimmunity and
      glomerulonephritis were assessed 20 and 40 weeks after pristane administration.
      Cell apoptosis, leukocyte accumulation, and cytokine levels in the peritoneal
      cavity of WT and MPO(-/-) mice were assessed 3 or 6 days after pristane
      injection. RESULTS: MPO(-/-) mice developed more severe nephritis than did WT
      mice 20 and 40 weeks after pristane injection, despite having reduced glomerular
      deposition of antibody and complement and diminished levels of markers of
      oxidative stress (oxidized DNA and glutathione sulfonamide). Enhancement of renal
      disease in MPO-deficient mice correlated with increased accumulation of CD4+ T
      cells and macrophages in glomeruli, which, in turn, was associated with augmented
      generation of CD4+ T cell responses and increased activation and migration of
      dendritic cells in secondary lymphoid organs. In addition, the enhanced renal
      injury in MPO(-/-) mice was associated with increased glomerular accumulation of
      neutrophils and deposition of neutrophil extracellular traps. MPO deficiency also
      increased early cell apoptosis, leukocyte accumulation, and proinflammatory
      cytokine expression in the peritoneum. CONCLUSION: MPO attenuates pristane
      induced LN by inhibiting early inflammatory responses in the peritoneum and
      limiting the generation of CD4+ T cell autoimmunity in secondary lymphoid organs.

PMID- 25777777
TI  - Distribution of intestinal metaplasia as a predictor of gastric cancer
      development.
AB  - BACKGROUND AND AIM: Helicobacter pylori, gastritis, and intestinal metaplasia
      (IM) are known risk factors for gastric cancer. In the present study, we
      conducted a cohort study to evaluate the predictive value of the distribution of
      IM for gastric cancer development. METHODS: We conducted a retrospective cohort
      study at a university hospital. From June 1998 to December 2000, we assessed
      histological gastritis using biopsy specimens, one from the antrum and one from
      the corpus, from 1450 patients, among whom 729 revisited for follow-up endoscopy.
      Patients were classified into three groups according to the distribution of IM at
      initial endoscopy. IM group A had no IM, IM group B had IM in the antrum only,
      and IM group C had IM in the corpus. The development of gastric cancer was
      assessed by endoscopic examination. RESULTS: The mean duration of follow-up was
      6.7 +/- 4.7 years. The cumulative incidence of gastric cancer at 5 years was 1.5%
      in total and 0.8%, 3.3%, and 2.7% in IM groups A, B, and C, respectively. The IM
      group was identified as an independent risk factor by multivariate analysis;
      compared with IM group A, hazard ratios were 3.6 (95% confidence interval [CI]
      1.1-12.1) in IM group B and 3.8 (95% CI 1.01-14.1) in IM group C. In IM group C,
      the incidence of gastric cancer in patients who received eradication therapy was
      significantly lower than that in patients who did not receive (P = 0.021, log
      rank). CONCLUSION: IM is a good predictive marker for the development of gastric
      cancer.

PMID- 25777778
TI  - Role of peptide-peptide interactions in aggregation: Protonectins observed in
      equilibrium and replica exchange molecular dynamics simulations.
AB  - Protonectin (ILGTILGLLKGL-NH2), a peptide extracted from the venom of the wasp
      Agelaia pallipes pallipes, promotes mast cell degranulation activity, antibiosis
      against Gram-positive and -negative bacteria, and chemotaxis in
      polymorphonucleated leukocytes. Another peptide from the same venom, Protonectin
      (1-6), corresponding to the first six residues of Protonectin, exhibits only
      chemotaxis. A 1:1 mixture of these two peptides showed positive synergistic
      antimicrobial effects, attributed to the formation of a heterodimer.16 The
      antimicrobial activity is probably related to the peptides' interaction with
      membrane phospholipids. Equilibrium and replica exchange molecular dynamics
      simulations were used to investigate two systems: the interaction of Protonectins
      (two molecules) and that of a mixture Protonectin and Protonectin (1-6) in the
      environment of sodium dodecyl sulfate (SDS) micelles, which mimic bacterial
      membranes and are also highly anionic. We found that in both systems the peptides
      tend to aggregate in the aqueous environment and are held together by hydrophobic
      interactions and hydrogen bonds. In the equilibrium simulations, aggregated
      Protonectin/Protonectin (1-6) dissociates after penetrating the SDS micelle,
      whereas the two Protonectins remain associated throughout the simulation time.
      Also, in the replica exchange simulations, the Protonectins remain closer,
      associating through a greater number of hydrogen bonds, and were found at only
      one free energy minimum, whereas the peptides in the mixture display other
      probable distances from each other, which are significantly longer than those
      observed with two Protonectin molecules. Coulomb contributions and the free
      energy of the systems containing micelles were calculated and show that the
      interactions of the mixed peptides are favored, whereas the interactions between
      pure Protonectins are more probable. As a consequence of the preferential
      interaction with the micelle, the Protonectin molecule of the mixed system
      presents a higher helical structure content. The enhancement of the amphipathic
      features caused by Protonectin (1-6) can be related to the increase in the
      antimicrobial activity experimentally observed. 

PMID- 25777779
TI  - Emerging role of microRNA-27a in human malignant glioma cell survival via
      targeting of prohibitin.
AB  - MicroRNAs (miRs) function as oncogenes and tumor suppressors, and have roles in
      most cellular processes. To date, the possible role of miR-27a, which is part of
      the miR-23a/27a/24-2 cluster, in malignant gliomas has remained elusive.
      Therefore, the present study aimed to explore the role of miR-27a in glioma and
      its potential target. Through transfection with miR-27a inhibitor or
      oligonucleotide mimics, the impact of miR-27a silencing or overexpression on the
      growth, apoptosis, cell cycle and invasiveness of U251 and U87MG cells was
      examined in vitro. The present study initially identified the potential target of
      miR-27a in glioma cells through a bioinformatics analysis, which was used for
      screening of the literature on the proteomics of gliomas. Prohibitin (PHB) was
      then confirmed as a target by absolute luciferase reporter assays, quantitative
      real-time polymerase chain reaction and western blot analysis. Treatment with miR
      27a mimics oligonucleotides suppressed U251 cell proliferation, promoted
      apoptosis by inducing G2/M phase arrest, and impaired the invasive potential of
      U251 cells in vitro. In addition, miR-27a expression was downregulated in glioma
      tissues. A PHB-3'-untranslated region luciferase reporter assay confirmed PHB as
      a direct target gene of miR-27a. PHB mRNA expression was reversely correlated
      with levels of miR-27a in U251 cells. Overexpression of miR-27a in U251 cells at
      72 h and 96 h post-transfection with miR-27a mimics significantly decreased PHB
      protein expression by 17.2% and 43.9%, respectively. In conclusion, miR-27a was
      shown to be a significant tumor suppressor by targeting and decreasing PHB
      protein expression in glioma U251 cells. miR-27a targeting of PHB may be a novel
      potential therapeutic strategy for glioma.

PMID- 25777780
TI  - Feasibility and diagnostic accuracy of exercise treadmill nitrogen-13 ammonia PET
      myocardial perfusion imaging of obese patients.
AB  - BACKGROUND: Treadmill exercise nitrogen-13 ((13)N)-ammonia positron emission
      tomography (PET) has logistical challenges and limited literature. We aimed to
      assess its feasibility, image quality, and diagnostic accuracy in obese and
      nonobese patients. METHODS AND RESULTS: Between 2009 and 2012, 10,804 patients
      were referred for myocardial perfusion imaging, including 300 for treadmill PET,
      of whom 265 were included in this study. Treadmill testing and PET were performed
      using standard procedures. Image quality, perfusion, and summed stress score
      (SSS) were assessed. Invasive coronary angiography was performed within 90 days
      of PET in 43 patients. Mean +/- SD body mass index (BMI) was 35.7 +/- 7.7 kg/m(2)
      (range 19.5-63.5 kg/m(2)). Feasibility of treadmill (13)N-ammonia PET was 100%.
      Exercise duration was less for obese patients than nonobese patients (P < .001).
      Image quality was rated good for 96.9% of obese and 100% of nonobese patients.
      For all patients, sensitivity was 86.4% and specificity was 74.4%. Diagnostic
      accuracy did not change significantly with increasing BMI. SSS remained
      significant in predicting angiographic coronary artery disease after adjustment
      for age, sex, and Duke treadmill score. CONCLUSIONS: Treadmill (13)N-ammonia PET
      is highly feasible, yields good image quality, and has moderately high diagnostic
      accuracy in a small subset of obese and nonobese patients who are deemed able to
      perform treadmill exercise.

PMID- 25777781
TI  - The reproducibility of time-of-flight PET and conventional PET for the
      quantification of myocardial blood flow and coronary flow reserve with (13)N
      ammonia.
AB  - BACKGROUND: This study aimed to validate the reproducibility of quantitative
      analysis using time-of-flight (TOF) and conventional PET with (13)N-ammonia
      ((13)N-NH3). METHODS AND RESULTS: Phantom images were reconstructed with and
      without TOF, and recovery coefficients (RCs) and the percent contrast of each
      sphere over the percent background variability were assessed. In the clinical
      study, 21 subjects underwent dynamic (13)N-NH3 PET scanning under stress and rest
      conditions. The dynamic acquisition images and intra- and inter-observer
      reproducibility of myocardial blood flow (MBF) and coronary flow reserve (CFR)
      were compared between reconstructions (with and without TOF). In the phantom
      study, RCs and the percent contrast of each sphere over the percent background
      variability was improved with TOF. In the clinical study, the noise of blood pool
      and myocardial images with TOF was less than that without TOF. Territorial and
      global intra- and inter-observer reproducibility of MBF and CFR values was
      excellent. Although segmental intra- and inter-observer reproducibility was
      excellent, there were larger variations in apex and the segment near the right
      ventricle (RV) without TOF. These variations became inconspicuous with TOF.
      CONCLUSION: Visual image quality, RCs, and percent contrast over percent
      background variability with TOF were better than that without TOF. Excellent
      correlations and good agreements in quantitative values were observed. TOF
      improved the variation of segmental values.

PMID- 25777783
TI  - SPECT attenuation artifact in a patient with a subcutaneous implantable
      cardioverter-defibrillator.

PMID- 25777782
TI  - Large Animal Models of Ischemic Cardiomyopathy: Are They Enough to Bridge the
      Translational Gap?

PMID- 25777784
TI  - Depression and anxiety during pregnancy and the postpartum period in women with
      epilepsy: A review of frequency, risks and recommendations for treatment.
AB  - PURPOSE: To review available data and provide treatment recommendations
      concerning peripartum depression, anxiety and fear of birth in women with
      epilepsy (WWE). METHOD: The PubMed, the LactMed, the DART and the Cochrane
      database were searched for original articles concerning psychiatric disease in
      the peripartum period in WWE. RESULTS: Point prevalence of depression from 2nd
      trimester to 6 months postpartum ranged from 16 to 35% in women with epilepsy
      compared to 9-12% in controls. The highest estimates were found early in
      pregnancy and in the perinatal period. Anxiety symptoms 6 months postpartum were
      reported by 10 and 5%, respectively. Fear of birth symptoms were increased in
      primiparous WWE compared to controls. Previous psychiatric disease,
      sexual/physical abuse, antiepileptic drug (AED) polytherapy, and high seizure
      frequency emerged as strong risk factors. Depressed WWE rarely used
      antidepressive medication during pregnancy. No evidence was available concerning
      treatment effects or impact on the developing child. CONCLUSION: Peripartum
      depression is frequent in WWE and seldom medically treated. Health personnel
      should screen WWE for psychiatric disease and risk factors during pre-pregnancy
      planning, pregnancy and postpartum follow up. Treatment decisions should rely on
      efficacy and safety data in peripartum patients without epilepsy and non-pregnant
      people with epilepsy. Consequences of in utero exposure to AED therapy in
      combination with antidepressants are not known, and non-pharmacological treatment
      should be tried first.

PMID- 25777785
TI  - Major congenital malformations in children of women with epilepsy.
AB  - It has been long known that the risk of major congenital malformations is
      increased among children of mothers with epilepsy. This is mainly due to the
      teratogenic effects of antiepileptic drugs although other factors, such as
      genetically determined individual susceptibility, are likely to contribute.
      Recent large scale prospective epilepsy and pregnancy registries have indicated
      that the rate of major congenital malformations may be at most two-fold higher
      than expected with exposure in utero to the presently most frequently used
      antiepileptic drugs such as carbamazepine or lamotrigine. Higher rates are
      consistently reported with exposure to valproate. The risk of teratogenic effects
      appears to be dose dependent and the lowest effective dose should thus be
      established before pregnancy regardless of which antiepileptic drug the woman is
      taking. Major changes such as switches between drugs should be avoided when
      pregnancy is established. 

PMID- 25777786
TI  - Trends on epidemiological, virological, and clinical features among newly
      diagnosed HIV-1 persons in Northwest Spain over the last 10 years.
AB  - To describe temporal trend and characteristics of newly HIV-diagnosed patients in
      a medical care area in Northwest Spain over the last 10 years. All newly
      diagnosed patients for HIV-infection from 2004 to 2013 at a reference medical
      care area in Northwest of Spain were identified. Epidemiological, virological,
      immunological, and clinical data, as well as HIV genotype and drug resistance
      information were recorded. A total of 565 newly HIV-diagnosed patients were
      identified. The number of new cases increased in the last 5 years (66
      cases/year). Overall, 53.1% had a median CD4 counts < 350 cells/ul and 33.6% had
      an AIDS defining criteria. Non-B variants were found in 34.4% of patients being
      subtype F (25.8%) the most common non-B subtype. The rate of transmitted drug
      resistance (TDR) over the study period was 3.7%, but a decreased to 2.6% was
      observed in the last 5 years. The most prevalent TDR mutations were: T215
      revertants (1.5%), K219QENR (1.2%), for NRTIs; K103N (1.9%), for NNRTIs; L90M
      (0.3%), for PIs. Overall, 73.2% of patients started antiretroviral treatment and
      9.9% of patients died during follow-up. The number of newly HIV diagnosed
      patients increased since year 2009. There is a high prevalence of late diagnosis
      (53%) and 33% had an AIDS defining criteria. Interestingly, the most prevalent
      non-B subtype in our population was F (25.8%). These findings support the need to
      facilitate the access for HIV testing to reduce the rate of late HIV diagnosis,
      improve the clinical outcome and prevent HIV transmission.

PMID- 25777788
TI  - Characterization of all possible single-nucleotide change caused amino acid
      substitutions in the kinase domain of Bruton tyrosine kinase.
AB  - Knowledge about features distinguishing deleterious and neutral variations is
      crucial for interpretation of novel variants. Bruton tyrosine kinase (BTK)
      contains the highest number of unique disease-causing variations among the human
      protein kinases, still it is just 10% of all the possible single-nucleotide
      substitution-caused amino acid variations (SNAVs). In the BTK kinase domain (BTK
      KD) can appear altogether 1,495 SNAVs. We investigated them all with
      bioinformatic and protein structure analysis methods. Most disease-causing
      variations affect conserved and buried residues disturbing protein stability.
      Minority of exposed residues is conserved, but strongly tied to pathogenicity.
      Sixty-seven percent of variations are predicted to be harmful. In 39% of the
      residues, all the variants are likely harmful, whereas in 10% of sites, all the
      substitutions are tolerated. Results indicate the importance of the entire kinase
      domain, involvement in numerous interactions, and intricate functional regulation
      by conformational change. These results can be extended to other protein kinases
      and organisms.

PMID- 25777789
TI  - Episodic foresight and anxiety: Proximate and ultimate perspectives.
AB  - OBJECTIVE: In this paper, we examine the relationship between episodic foresight
      and anxiety from an evolutionary perspective, proposing that together they confer
      an advantage for modifying present moment decision-making and behaviour in the
      light of potential future threats to fitness. METHODS: We review the body of
      literature on the role of episodic foresight in anxiety, from both proximate and
      ultimate perspectives. RESULTS: We propose that anxious feelings associated with
      episodic simulation of possible threat-related future events serve to imbue these
      simulations with motivational currency. Episodic and semantic details of a future
      threat may be insufficient for motivating its avoidance, but anxiety associated
      with a simulation can provoke adaptive threat management. As such, we detail how
      anxiety triggered by a self-generated, threat-related future simulation prepares
      the individual to manage that threat (in terms of its likelihood and/or
      consequences) over greater temporal distances than observed in other animals. We
      then outline how anxiety subtypes may represent specific mechanisms for
      predicting and managing particular classes of fitness threats. CONCLUSIONS: This
      approach offers an inroad for understanding the nature of characteristic future
      thinking patterns in anxiety disorders and serves to illustrate the adaptive
      function of the mechanism from which clinical anxiety deviates.

PMID- 25777787
TI  - Novel microbiome-based therapeutics for chronic rhinosinusitis.
AB  - The human microbiome, i.e. the collection of microbes that live on, in and
      interact with the human body, is extraordinarily diverse; microbiota have been
      detected in every tissue of the human body interrogated to date. Resident
      microbiota interact extensively with immune cells and epithelia at mucosal
      surfaces including the airways, and chronic inflammatory and allergic respiratory
      disorders are associated with dysbiosis of the airway microbiome. Chronic
      rhinosinusitis (CRS) is a heterogeneous disease with a large socioeconomic
      impact, and recent studies have shown that sinus inflammation is associated with
      decreased sinus bacterial diversity and the concomitant enrichment of specific
      sinus pathogens. Here, we discuss the potential role for probiotic
      supplementation for CRS in light of this increasing understanding of the airway
      microbiome and microbial interactions with the host. We focus on the ecological
      significance of microbiome-based probiotic supplementation and potential
      interactions with the gastrointestinal tract and consider microbial
      administration methods for treatment of CRS. 

PMID- 25777790
TI  - Evaluation of carnitine deficit in very low birth weight preterm newborns small
      for their gestational age.
AB  - OBJECTIVE: To verify whether small-for-gestational-age (SGA) preterm newborns
      represent a special risk group for carnitine deficiency. Secondary outcome
      includes assessment of longitudinal differences of total carnitine (TC), free
      carnitine (FC) and acylcarnitines between SGA and appropriate-for-gestational-age
      (AGA). METHODS: A retrospective study to evaluate carnitine and acylcarnitines
      profile on 144 very-low-birth weight newborns (VLBW), classified as AGA (n = 73)
      and SGA (n = 71), was performed by tandem mass spectrometry, during their first 5
      weeks of life. Carnitine deficiency was defined as FC <40 umol/L and FC/TC <0.7.
      RESULTS: Carnitine deficiency was observed in the two study groups throughout the
      monitoring period (maximum FC: 36.05 umol/L in AGA and 32.24 umol/L in SGA).
      FC/TC remains under 0.7 in both with progressive improvement. Unlike expected, a
      comparatively higher value of TC, FC and total acylcarnitines (tAC) was found in
      SGA during the first 2 weeks, with significant relevance on day 3-5, especially
      for tAC (p < 0.001). The only acylcarnitine with persistently lower value in SGA
      is C5 (p < 0.05 in first 2 weeks). CONCLUSIONS: A carnitine deficiency was
      demonstrated in all VLBW. Although birth weight restriction has been suggested as
      a risk factor for impaired carnitine status, in our study, SGA was not related
      with higher carnitine deficiency.

PMID- 25777791
TI  - Is antenatal depression associated with adverse obstetric and perinatal outcomes?
AB  - OBJECTIVE: To examine whether a pre-gestational diagnosis of depression is a risk
      factor for adverse obstetric and neonatal outcome. STUDY DESIGN: A retrospective
      cohort study investigating maternal characteristics, obstetrical and perinatal
      outcomes in singleton pregnancies of women with and without a diagnosis of
      depression was conducted. A pre-gestational diagnosis of depression was made by a
      psychiatrist or family physician and was recorded in the patients' chart.
      Multiple logistic regression models were used to control for possible
      confounders. RESULTS: During the study period, 256 312 deliveries occurred. Of
      which, 221 women (0.1%) had a pre-gestational diagnosis of depression. When
      examining obstetric outcomes, women with a diagnosis of depression were older
      (32.05 +/- 5.772 versus 28.56 +/- 5.851) and smokers (7.2% versus 1.1%), had a
      higher rate of preterm deliveries (37.99 +/- 2.989 versus 39.02 +/- 2.249) and
      cesarean sections (CS; 28.5% versus 13.6%) in comparison to the control group.
      When examining neonatal outcomes, neonates of women diagnosed with depression had
      a lower birth mean weight (3.038.47 +/- 649.6 versus 3183.44 +/- 551.8) and
      increased rates of perinatal mortality (3.2% versus 1.3%). Using a multiple
      logistic regression model, with perinatal mortality as the outcome variable to
      control for cofounders such as maternal age, preterm birth, chronic hypertension
      and gestational diabetes mellitus, a diagnosis of depression was not found to be
      an independent risk factor for perinatal mortality. Another multiple logistic
      regression model found advanced maternal age, smoking, preterm birth and labor
      induction to be associated with a diagnosis of depression. CONCLUSION: Pregnant
      women diagnosed with depression are at an increased risk for preterm birth, low
      birth weight, and CSs. However, it was not associated with increased rates of
      perinatal mortality.

PMID- 25777792
TI  - Placental calcifications: a clue for the identification of high-risk fetuses in
      the low-risk pregnant population?
AB  - "What does it mean, Doctor?" and "Is it going to affect my baby in some way?".
      Those are the most typical questions of pregnant women to obstetricians.
      Answering is sometimes easier but placental calcification is not the case, since
      placental architecture and disease are two different faces of the same coin and
      the association between them is not completely clear. Placenta can function
      properly, even in the presence of architectural alterations, without any fetal
      consequences. So, remains the question, when does a placental structural anomaly
      become a sign of increased attention to maternal conditions, fetal development
      and well-being? The present review will analyze these concepts, with emphasis on
      placental calcification, its pathogenesis, and the state-of-the-art regarding the
      influence of this finding on pregnancy outcomes among low-risk pregnant patients.

PMID- 25777793
TI  - Evaluation of bone metabolism in newborn twins using quantitative ultrasound and
      biochemical parameters.
AB  - Metabolic bone disease (MBD) is one of the important complications of
      prematurity. Early and adequate nutritional interventions may reduce the
      incidence and potential complications of MBD. The present study aimed to evaluate
      bone metabolism in twins via biochemical parameters and quantitative ultrasound
      (QUS) and to compare the results between twin pairs. Moreover, twin infants were
      evaluated in terms of potential risk factors likely to have impact on MBD. Forty
      three pairs of twins were included in the study. Serum calcium, phosphorus,
      magnesium, and alkaline phosphatase concentrations were assessed and bone mineral
      density was measured using QUS (speed of sound, SOS) at postnatal 30 d. Co-twin
      with the higher birth weight was assigned to Group 1 (n = 36) and the other twin
      was assigned to Group 2 (n = 36). Birth weight and head circumference were
      significantly higher in the infants of Group 1 compared with Group 2. No
      significant difference was found among the groups in terms of gender, history of
      resuscitation, length of stay in intensive care unit (ICU) or in the incubator,
      duration of total parenteral nutrition (TPN), type of nutrition, vitamin D use,
      biochemical parameters, and the SOS value. The factors likely to affect SOS,
      including type of pregnancy, maternal drug use, gender of infant, birth weight,
      head circumference at birth, gestational week, length of stay at the ICU,
      duration of TPN, type of nutrition, resuscitation, vitamin D use, and levels of
      calcium, phosphorus, magnesium, and alkaline phosphatase were entered into the
      model. The phosphorus level and the maternal drug use were found to be the
      factors that significantly reduced SOS, whereas pregnancy after assisted
      reproductive techniques was found to be a significant enhancing factor. 

PMID- 25777794
TI  - The effect of intrapartum dental support use among nulliparous during the second
      stage of labor - a randomized controlled study.
AB  - OBJECTIVE: We aimed to determine the effect of a dental support device (DSD) use
      on the course of labor and delivery in nulliparous women. METHODS: A randomized,
      controlled, open-label study of nulliparous (at 37 + 0/7 and 41 + 3/7 weeks of
      gestation) in a single tertiary university-affiliated medical center. Exclusion
      criteria included maternal chronic diseases, multi-fetal gestation and fetal
      chromosomal or structural anomalies. Outcomes were analyzed according to the
      actual use of the DSD, and satisfaction questionnaires following delivery.
      RESULTS: Overall, 191 women were randomized (93in the study group and 98 in the
      control group). The median duration of the second stage was similar between the
      groups (100.0 +/- 91.0 versus 98.0 +/- 128.8 min, p = 0.97) and the maximal VAS
      score was significantly higher in the DSD group (4.0 +/- 8.5 versus 3.0 +/- 6.8,
      p = 0.04). The rate of obstetrical interventions such as operative vaginal
      delivery or cesarean section during the second stage was significantly higher in
      the control group than in the study group (28.2% versus 12.3% and 6.4% versus
      1.2%, respectively, p = 0.004), mainly due to prolonged second stage of labor
      (24.5% versus 8.6%, p = 0.005). Of the DSD group, 50.6% rated the use of the DSD
      as comfortable, 32.2% rated its effect on pain relief as high, 55.6% would
      recommend its use to their peers and 51.9% would like to use it in their
      consecutive delivery. CONCLUSION: The use of a DSD among nulliparous women
      appears to decrease the need for obstetrical intervention due to prolonged second
      stage of labor, with fair satisfaction of patients.

PMID- 25777795
TI  - Sex differences in skeletal muscle phosphatase and tensin homolog deleted on
      chromosome 10 (PTEN) levels: a cross-sectional study.
AB  - Women have higher adiposity but maintain insulin sensitivity when compared to
      men. Phosphatase and tensin homolog deleted on chromosome 10 (PTEN) inhibits
      insulin signaling, but it is not known if PTEN regulate insulin resistance in a
      sex-specific manner. In this cross-sectional study, muscle biopsies from
      participants in the Molecular Study of Health and Risk in Ethnic Groups (Mol
      SHARE) were used to test for sex differences in PTEN expression. Quantitative
      real-time PCR was performed to determine PTEN gene expression (n = 53), and
      western blotting detected total and phosphorylated PTEN protein (n = 36). Study
      participants were comparable in age and body mass index. Women had higher fat
      mass percentage compared to men (40.25 +/- 9.9% in women versus 27.6 +/- 8.8% in
      men; mean difference -0.18, 95%CI (-0.24, -0.11), p-value <0.0001), with similar
      HOMA-IR (2.46 +/- 2.05 in men versus 2.34 +/- 3.06 in women; mean difference
      0.04; 95% CI (-0.12, 0.21), p-value 0.59). Women had significant downregulation
      of PTEN gene expression (p-value 0.01) and upregulation of PTEN protein
      phosphorylation (inactivation) (p-value 0.001) when compared to men after
      correction for age, ethnicity, HOMA-IR, fat mass and sex. We conclude that the
      downregulation of muscle PTEN may explain the retention of insulin sensitivity
      with higher adiposity in women compared to men. 

PMID- 25777796
TI  - Spotlight on movement disorders: What optogenetics has to offer.
AB  - Elucidating the neuronal mechanisms underlying movement disorders is a major
      challenge because of the intricacy of the relevant neural circuits, which are
      characterized by diverse cell types and complex connectivity. A major limitation
      of traditional techniques, such as electrical stimulation or lesions, is that
      individual elements of a neural circuit cannot be selectively manipulated.
      Moreover, available treatments are largely based on trial and error rather than a
      detailed understanding of the circuit mechanisms. Gaps in our knowledge of the
      circuit mechanisms for movement disorders, as well as mechanisms underlying known
      treatments such as deep brain stimulation, make it difficult to design new and
      improved treatment options. In this perspective, we discuss how optogenetics,
      which allows researchers to use light to manipulate neuronal activity, can
      contribute to the understanding and treatment of movement disorders. We outline
      the advantages and limitations of optogenetics and discuss examples of studies
      that have used this tool to clarify the role of the basal ganglia circuitry in
      movement.

PMID- 25777797
TI  - miRNA in situ hybridization in circulating tumor cells--MishCTC.
AB  - Circulating tumor cells (CTCs) must be phenotypically and genetically
      characterized before they can be utilized in clinical applications. Here, we
      present the first protocol for the detection of miRNAs in CTCs using in situ
      hybridization (ISH) combined with immunomagnetic selection based on cytokeratin
      (CK) expression and immunocytochemistry. Locked-Nucleic Acid (LNA) probes
      associated with an enzyme-labeled fluorescence (ELF) signal amplification
      approach were used to detect miRNA-21 in CTCs. This protocol was optimized using
      both epithelial tumor (MDA-MB468) and epithelial non-tumor (MCF-10A) cell lines,
      and miRNA-21 was selected as the target miRNA because of its known role as an
      onco-miRNA. Hematopoietic cells do not express miRNA-21; thus, miRNA-21 is an
      ideal marker for detecting CTCs. Peripheral blood samples were taken from 25
      cancer patients and these samples were analyzed using our developed protocol. Of
      the 25 samples, 11 contained CTCs. For all 11 CTC-positive samples, the isolated
      CTCs expressed both CK and miRNA-21. Finally, the protocol was applied to monitor
      miRNA-21 expression in epithelial to mesenchymal transition (EMT)-induced MCF-7
      cells, an epithelial tumor cell line. CK expression was lost in these cells,
      whereas miRNA-21 was still expressed, suggesting that miRNA-21 might be a good
      marker for detecting CTCs with an EMT phenotype. 

PMID- 25777798
TI  - Assessing the public health impacts of legalizing recreational cannabis use in
      the USA.
AB  - A major challenge in assessing the public health impact of legalizing cannabis
      use in Colorado and Washington State is the absence of any experience with legal
      cannabis markets. The Netherlands created a de facto legalized cannabis market
      for recreational use, but policy analysts disagree about how it has affected
      rates of cannabis use. Some US states have created de facto legal supply of
      cannabis for medical use. So far this policy does not appear to have increased
      cannabis use or cannabis-related harm. Given experience with more liberal alcohol
      policies, the legalization of recreational cannabis use is likely to increase use
      among current users. It is also likely that legalization will increase the number
      of new users among young adults but it remains uncertain how many may be
      recruited, within what time frame, among which groups within the population, and
      how many of these new users will become regular users. 

PMID- 25777799
TI  - Phosphorylated 5-ethynyl-2'-deoxyuridine for advanced DNA labeling.
AB  - The representative DNA-labeling agent 5-ethynyl-2'-deoxyuridine (EdU) was
      chemically modified to improve its function. Chemical monophosphorylation was
      expected to enhance the efficiency of the substrate in DNA polymerization by
      circumventing the enzymatic monophosphorylation step that consumes energy. In
      addition, to enhance cell permeability, the phosphates were protected with bis
      pivaloyloxymethyl that is stable in buffer and plasma, and degradable inside
      various cell types. The phosphorylated EdU (PEdU) was less toxic than EdU, and
      had the same or a slightly higher DNA-labeling ability in vitro. PEdU was also
      successfully applied to DNA labeling in vivo. In conclusion, PEdU can be used as
      a less toxic DNA-labeling agent for studies that require long-term cell survival
      or very sensitive cell lines. 

PMID- 25777800
TI  - Well-defined palladium nanoparticles supported on siliceous mesocellular foam as
      heterogeneous catalysts for the oxidation of water.
AB  - Herein, we describe the use of Pd nanoparticles immobilized on an amino
      functionalized siliceous mesocellular foam for the catalytic oxidation of H2O.
      The Pd nanocatalyst proved to be capable of mediating the four-electron oxidation
      of H2O to O2, both chemically and photochemically. The Pd nanocatalyst is easy to
      prepare and shows high chemical stability, low leaching, and recyclability.
      Together with its promising catalytic activity, these features make the Pd
      nanocatalyst of potential interest for future sustainable solar-fuel production.

PMID- 25777801
TI  - Association between thyrotropin levels and insulin sensitivity in euthyroid obese
      adolescents.
AB  - BACKGROUND: Thyrotropin (TSH) levels display a positive association with body
      mass index (BMI), and the prevalence of isolated hyperthyrotropinemia is higher
      in obese adolescents compared to their normal weight controls. However, the
      metabolic significance of the higher TSH in obese adolescents is less clear. The
      objective of this study was to determine the relationship between TSH
      concentrations and insulin sensitivity, lipids, and adipokines in euthyroid, non
      diabetic, obese adolescents. METHODS: Thirty-six euthyroid, non-diabetic, obese
      adolescents between the ages of 12 and 18 years underwent a 75 g oral glucose
      tolerance test. Insulin sensitivity (Si) and pancreatic beta-cell function as
      assessed by disposition index (DI) were measured using the oral glucose minimal
      model approach. Cholesterol (total, low-density lipoprotein [LDL-C], and high
      density lipoprotein [HDL-C]), triglycerides (TG), interleukin-6 (IL-6), total and
      high molecular weight (HMW) adiponectin, and retinol binding protein-4 (RBP4)
      were also determined. Associations between measures of thyroid function and Si,
      DI, lipids, and adipokines were computed using Pearson's correlation coefficient
      and multiple regression analysis. RESULTS: The mean age of the subjects was
      14.3+/-1.88 years, and the mean BMI was 32.5+/-4.65 kg/m2; 97% were non-Hispanic
      white and 47% were male. The mean TSH was 2.7+/-1.2 mIU/L. Increasing serum TSH
      was correlated with decreasing Si (log Si) in the entire cohort (p=0.03), but
      this relationship persisted only in males (p=0.02). The correlation between TSH
      and Si in males remained significant after adjusting for BMI (p=0.02). There was
      no correlation between TSH and pancreatic beta-cell function as assessed by DI
      (p=0.48). TSH correlated positively with LDL-C (p=0.04) and IL-6 (p=0.03), but
      these associations vanished or weakened after adjusting for BMI (LDL-C p
      value=0.44; IL-6 p-value=0.07). CONCLUSIONS: This study suggests a sex-specific
      association between TSH and insulin sensitivity in euthyroid, non-diabetic, obese
      adolescent males. Prospective studies are warranted to explore further this
      sexual dimorphism in the relationship between thyroid function and insulin
      sensitivity and to determine if obese adolescents with insulin resistance
      receiving thyroid supplements for hypothyroidism would benefit from targeting TSH
      levels in the lower half of normal range.

PMID- 25777802
TI  - Management of nosocomial scabies, an outbreak of occupational disease.
AB  - BACKGROUND: The optimal approach to managing institutional scabies outbreaks has
      yet to be defined. We report on outbreak managements are needed. METHODS: We
      report on a large outbreak of scabies in three acute care wards in a tertiary
      university teaching hospital in the Netherlands. RESULTS: The outbreak
      potentially effected 460 patients and 185 health care workers who had been
      exposed to the index patient. CONCLUSION: Containment of an outbreak relies on a
      quick and strict implementation of appropriate infection control measures and
      should include simultaneous treatment of all infested persons and exposed
      contacts to prevent secondary spread and prolonged post-intervention
      surveillance.

PMID- 25777803
TI  - Treatment Algorithms in Systemic Lupus Erythematosus.
AB  - OBJECTIVE: To establish agreement on systemic lupus erythematosus (SLE)
      treatment. METHODS: SLE experts (n = 69) were e-mailed scenarios and indicated
      preferred treatments. Algorithms were constructed and agreement determined (>=50%
      respondents indicating >=70% agreement). RESULTS: Initially, 54% (n = 37)
      responded suggesting treatment for scenarios; 13 experts rated agreement with
      scenarios. Fourteen of 16 scenarios had agreement as follows: discoid lupus:
      first-line therapy was topical agents and hydroxychloroquine and/or
      glucocorticoids then azathioprine and subsequently mycophenolate (mofetil);
      uncomplicated cutaneous vasculitis: initial treatment was glucocorticoids +/-
      hydroxychloroquine +/- methotrexate, followed by azathioprine or mycophenolate
      and then cyclophosphamide; arthritis: initial therapy was hydroxychloroquine
      and/or glucocorticoids, then methotrexate and subsequently rituximab;
      pericarditis: first-line therapy was nonsteroidal antiinflammatory drugs, then
      glucocorticoids with/without hydroxychloroquine, then azathioprine,
      mycophenolate, or methotrexate and finally belimumab or rituximab, and/or a
      pericardial window; interstitial lung disease/alveolitis: induction was
      glucocorticoids and mycophenolate or cyclophosphamide, then rituximab or
      intravenous gamma globulin (IVIG), and maintenance followed with azathioprine or
      mycophenolate; pulmonary hypertension: glucocorticoids and mycophenolate or
      cyclophosphamide and an endothelin receptor antagonist were initial therapies,
      subsequent treatments were phosphodiesterase-5 inhibitors and then prostanoids
      and rituximab; antiphospholipid antibody syndrome: standard anticoagulation
      with/without hydroxychloroquine, then a thrombin inhibitor for venous thrombosis,
      versus adding aspirin or platelet inhibition drugs for arterial events;
      mononeuritis multiplex and central nervous system vasculitis: first-line therapy
      was glucocorticoids and cyclophosphamide followed by maintenance with
      azathioprine or mycophenolate, and then rituximab, IVIG, or plasmapheresis; and
      serious lupus nephritis: first-line therapy was glucocorticoids and
      mycophenolate, then cyclophosphamide then rituximab. CONCLUSION: We established
      variable agreement on treatment approaches. For some treatment decisions there
      was good agreement between experts even if no randomized controlled trial data
      were available.

PMID- 25777810
TI  - Erratum to: Reduced length of stay in radical cystectomy patients with oral
      versus parenteral post-operative nutrition protocol.

PMID- 25777804
TI  - Early life body fatness and risk of colorectal cancer in u.s. Women and men
      results from two large cohort studies.
AB  - BACKGROUND: The association between body fatness before adulthood and later risk
      of colorectal cancer remains unclear. We hypothesized that, independent of adult
      body fatness, early life body fatness would be associated with a higher risk of
      developing colorectal cancer. METHODS: We assessed body fatness during childhood
      and adolescence using a validated 9-level somatotype and inquired body weight in
      young adulthood in the Nurses' Health Study and Health Professionals Follow-up
      Study. We used the Cox proportional hazard regression modeling to estimate
      relative risks [RR, 95% confidence intervals (CI)] adjusting for adult body mass
      index (BMI) and other known colorectal cancer risk factors. RESULTS: We
      identified 2,100 incident colorectal cancer cases (1,292 in women and 808 in men)
      during 22 years of follow-up. Among women, the RR (95% CI) for childhood body
      fatness of level 5 or higher versus level 1 was 1.28 (1.04-1.58; Ptrend = 0.08)
      and for adolescent body fatness, it was 1.27 (1.01-1.60; Ptrend = 0.23). The
      corresponding RRs for men were 1.04 (0.82-1.31; Ptrend = 0.48) and 0.98 (0.75
      1.27; Ptrend = 0.20), respectively. Results were generally similar across
      anatomic subsites within the colorectum. In addition, the RRs comparing BMI
      categories >=27.5 to <19 kg/m(2) were 1.44 (1.06-1.95, at age 18; Ptrend = 0.009)
      for women and 1.18 (0.84-1.65, at age 21; Ptrend = 0.57) for men. CONCLUSION:
      Increased body fatness in early life, independent of adult obesity, might be a
      risk factor for colorectal cancer in women, but we observed a weaker association
      in men. IMPACT: Our findings support the growing evidence that early life body
      fatness affects the risk of colorectal cancer many decades later.

PMID- 25777811
TI  - Acetylcholine Suppresses Ventricular Arrhythmias and Improves Conduction and
      Connexin-43 Properties During Myocardial Ischemia in Isolated Rabbit Hearts.
AB  - INTRODUCTION: Acetylcholine (ACh), a vagal efferent neurotransmitter, markedly
      improves survival in rats with myocardial ischemia (MI) by preventing ischemic
      loss of gap junction (Gj) and by inducing anti-apoptotic cascades. However,
      electrophysiological mechanisms of the antiarrhythmic effect of ACh after acute
      MI are still unclear. METHODS: Acute MI was induced by ligation of the left
      anterior descending (LAD) coronary artery in Langendorff-perfused rabbit hearts
      with (ACh(+):n = 11) or without (ACh(-):n = 12) 10 MUmol/L ACh delivered
      continuously starting at 5 minutes before LAD ligation. Action potentials on the
      left ventricular (LV) anterior surface (~2*2 cm) were recorded by optical mapping
      during pacing from the LV epicardium (BCL = 500 milliseconds). Conduction
      velocities (CVs) at 256 sites were calculated and the ventricular
      tachycardia/ventricular fibrillation (VT/VF) susceptibility was also assessed by
      programmed electrical stimulation before and 30 minutes after MI. The amount and
      distribution of Gj protein connexin-43 was analyzed by immunoblotting and
      immunohistochemistry. RESULTS: Averaged CV in the ischemic border zone (IBZ) was
      significantly slower in ACh(-) than in ACh(+) (21 +/- 7 vs. 34 +/- 6 cm/s; P <
      0.01). Short-coupled extra stimulus further decreased CV of IBZ in ACh(-) (13 +/-
      4 cm/s) but did not change that in ACh(+) (34 +/- 5 cm/s), leading to a high
      incidence of conduction block in IBZ in ACh(-) but not in ACh(+) (83% vs. 0%).
      VT/VF after MI were induced in ACh(-) but suppressed in ACh(+) (10/12 vs. 3/11; P
      < 0.01). Connexin-43 in the LV anterior wall was significantly reduced after MI
      in ACh(-) but not in ACh(+). CONCLUSION: ACh may suppress VT/VF by preventing
      loss of Gj and improving CV in IBZ during acute MI.

PMID- 25777813
TI  - In vivo biocompatibility of custom-fabricated apatite-wollastonite-mesenchymal
      stromal cell constructs.
AB  - We have used the additive manufacturing technology of selective laser sintering
      (SLS), together with post SLS heat treatment, to produce porous three dimensional
      scaffolds from the glass-ceramic apatite-wollastonite (A-W). The A-W scaffolds
      were custom-designed to incorporate a cylindrical central channel to increase
      cell penetration and medium flow to the center of the scaffolds under dynamic
      culture conditions during in vitro testing and subsequent in vivo implantation.
      The scaffolds were seeded with human bone marrow mesenchymal stromal cells (MSCs)
      and cultured in spinner flasks. Using confocal and scanning electron microscopy,
      we demonstrated that MSCs formed and maintained a confluent layer of viable cells
      on all surfaces of the A-W scaffolds during dynamic culture. MSC-seeded, with and
      without osteogenic pre-differentiation, and unseeded A-W scaffolds were implanted
      subcutaneously in MF1 nude mice where osteoid formation and tissue in-growth were
      observed following histological assessment. The results demonstrate that the in
      vivo biocompatibility and osteo-supportive capacity of A-W scaffolds can be
      enhanced by SLS-custom design, without the requirement for osteogenic pre
      induction, to advance their potential as patient-specific bone replacement
      materials.

PMID- 25777812
TI  - Sialic acids: biomarkers in endocrinal cancers.
AB  - Sialylations are post translational modification of proteins and lipids that play
      important role in recognition, signaling, immunological response and cell-cell
      interaction. Improper sialylations due to altered sialyl transferases,
      sialidases, gene structure and expression, sialic acid metabolism however lead to
      diseases and thus sialic acids form an important biomarker in disease. In the
      endocrinal biology such improper sialylations including altered expression of
      sialylated moieties have been shown to be associated with disorders. Cancer still
      remains to be the major cause of global death and the cancer of the endocrine
      organs suffer from the dearth of appropriate markers for disease prediction at
      the early stage and monitoring. This review is aimed at evaluating the role of
      sialic acids as markers in endocrinal disorders with special reference to cancer
      of the endocrine organs. The current study is summarized under the following
      headings of altered sialylations in endocrinal cancer of the (i) ovary (ii)
      pancreas (iii) thyroid (iv) adrenal and (v) pituitary gland. Studies in
      expression of sialic acid in testis cancer are limited. The future scope of this
      review remains in the targeting of endocrinal cancer by targeting altered
      sialylation which is a common expression associated with endocrinal cancer. 

PMID- 25777814
TI  - Negative symptoms in schizophrenia show association with amygdala volumes and
      neural activation during affective processing.
AB  - OBJECTIVES: Negative symptoms in schizophrenia have been associated with
      structural and functional alterations of the amygdala. We hypothesised that there
      would be between-group differences in amygdala volume and neural activation
      patterns during processing of affective stimuli among patients with schizophrenia
      and healthy controls. We further hypothesised correlations between neuroimaging
      metrics and clinical ratings of negative symptoms in patients with schizophrenia.
      METHODS: We used structural and functional magnetic resonance imaging to assess
      volume and neural activation of the amygdala in 28 patients with schizophrenia
      and 28 healthy controls. RESULTS: We found no between-group differences in
      amygdala volume or neural activation. However, we found a significant negative
      correlation between emotional blunting and neural activation in the left amygdala
      during processing of positive affect. We also found a significant negative
      correlation between stereotyped thinking and the volume of right amygdala.
      CONCLUSION: Our findings implicate the amygdala in a subgroup of negative
      symptoms in schizophrenia that are characterised by reduced expression with
      blunted affect and stereotyped thinking.

PMID- 25777815
TI  - Comparison of intravitreal bevacizumab and dexamethasone implant for the
      treatment of macula oedema associated with branch retinal vein occlusion.
AB  - BACKGROUND/AIMS: To compare the functional and anatomical outcomes of
      intravitreal bevacizumab (IVB) with those of dexamethasone implant injection
      (IVD) for macular oedema associated with branch retinal vein occlusion (BRVO).
      METHODS: Seventy-two patients with centre-involving macular oedema secondary to
      BRVO were retrospectively enrolled in the study; these patients were treated with
      either 1.25 mg IVB (44 eyes; mean injections: 2.92+/-1.38) pro re nata (PRN) by
      follow-up monthly or 700 ug IVD (28 eyes; mean injections: 1.71+/-0.47) given at
      6-month intervals PRN and were followed for at least 12 months. Main outcome
      measures were changes in best-corrected visual acuity (BCVA) and central foveal
      thickness (CFT). RESULTS: There was no statistically significant difference of
      mean change of the logarithm of the minimum angle of resolution BCVA between IVB
      and IVD groups at monthly visits, up to 12 months (all p>0.05); however, there
      was a trend towards greater BCVA gain in the IVB group than in the IVD group at 6
      months (p=0.053). Additionally, 52.6% in the IVB group and 50% in the IVD group
      gained two or more lines of Snellen visual acuity at 12 months (p=0.85). The mean
      CFT decreased by 160 um for the IVB group and by 140.7 um for the IVD group at 12
      months. Both the IVB group and the IVD group achieved statistically similar
      improvement of CFT at monthly visits, up to 5 months (all p>0.05); however, the
      CFT began to deteriorate after 5 months in the IVD group, and at 6 months,
      improvement in the IVB group was significantly greater than that in the IVD group
      (p=0.007). After a second IVD injection at 6 months, the IVD group showed
      significant improvement of CFT, and there was no significant difference of CFT
      change between the IVB and IVD groups until 12 months. CONCLUSIONS: For macular
      oedema secondary to BRVO, IVB administered PRN monthly and IVD administered PRN
      at 6-month intervals, yielded functionally and anatomically comparable outcomes
      at 12 months.

PMID- 25777816
TI  - Aflibercept therapy for polypoidal choroidal vasculopathy: short-term results of
      a multicentre study.
AB  - BACKGROUND/AIMS: To investigate short-term outcomes of intravitreal aflibercept
      injections (IAIs) for polypoidal choroidal vasculopathy (PCV). METHODS: 91 eyes
      of 88 consecutive patients with treatment-naive PCV examined at three university
      hospitals received IAI monthly for 3 months. One month after the third IAI,
      changes in best-corrected visual acuity (BCVA) and macular morphology were
      retrospectively evaluated. Additionally, possible baseline characteristics
      predictive of persistent retinal fluid were analysed. RESULTS: The mean BCVA
      (logarithm of the minimum angle of resolution units) of the 91 eyes improved from
      0.31 at baseline to 0.21 at 3 months (p<0.0001). The mean central retinal
      thickness and mean subfoveal choroidal thickness decreased from 323 MUm and 270
      MUm at baseline to 185 MUm and 232 MUm at 3 months, respectively (p<0.0001 for
      both). Seventy-three eyes (80.2%) achieved a dry macula defined as absence of
      retinal fluid. Presence of the baseline characteristics of subretinal haemorrhage
      and greater size of the largest polyp were significantly associated with
      inability to achieve a dry macula (p=0.008 and 0.03, respectively). However, this
      association was not found on multivariate logistic regression. Of the 90 eyes
      that underwent indocyanine green angiography at 3 months, 43 eyes (47.8%) showed
      complete and 28 eyes (31.1%) showed partial resolution of polyps. Twenty-four
      eyes (24.4%) also showed partial regression of branching choroidal vascular
      networks. CONCLUSIONS: IAIs for the treatment of a large number of PCV eyes were
      found to improve both visual acuity and macular morphology over the short term.

PMID- 25777817
TI  - Cupping of the optic disk after methanol poisoning.
AB  - PURPOSE: To assess the frequency and significance of optic disk cupping after
      methanol poisoning. METHODS: We retrospectively reviewed the medical records of
      50 consecutive patients with methanol poisoning, including visual acuity,
      pupillary reaction, and optic disk features such as the presence and degree of
      cupping. All patients were examined in the chronic phase after optic nerve
      damage. RESULTS: Optic disk cupping >=0.8 c/d was present in at least one eye of
      22 of these 50 patients (43/100 eyes). Severity of cupping was statistically
      symmetric in the two eyes, and increasing severity of cupping was correlated with
      worse visual acuity (p=0.007) and increasing visual field loss. Degree of cupping
      was significantly correlated with increasing patient age but not with putaminal
      necrosis. CONCLUSIONS: Optic disk cupping after methanol poisoning may be more
      common than previously recognised. Cupping in this setting may reflect toxicity
      of methanol metabolites to axons and glial cells in the prelaminar, laminar and
      retrolaminar regions, and seems to be important as a marker for worse optic nerve
      damage.

PMID- 25777819
TI  - Aspergillus oryzae fermented germinated soybean extract alleviates perimenopausal
      symptoms in ovariectomised rats.
AB  - BACKGROUND: Soybeans have been widely used to alleviate climacteric symptoms. In
      this study, we investigated the oestrogenic activities of isoflavones extracted
      from Aspergillus oryzae-challenged germinated soybeans (AO-GS). Eight-week-old
      virgin Sprague-Dawley female rats were ovariectomised (OVX). The rats were orally
      administered 0.1 mg kg(-1) 17alpha-ethinyl oestradiol or three different doses of
      AO-GS (0.5, 1.0 2.0 g kg(-1) day(-1)) in distilled water for 6 weeks, while
      control rats were administered vehicle alone. Uterine weights and levels of
      oestradiol and testosterone in serum were measured. In addition to serum
      parameters, bone parameters were also acquired by using micro-computed tomography
      scanning. RESULTS: Treatments of OVX rats with AO-GS changed the secretory
      profile of serum oestradiol and testosterone. Serum oestradiol levels were
      significantly increased in OVX rats treated with and AO-GS (0.5, 1.0, 2.0 g kg(
      1) day(-1)), while serum testosterone levels were not significantly increased in
      OVX rats treated with 1.0 g kg(-1) day(-1) of AO-GS. Furthermore, AO-GS (2.0 g
      kg(-1) day(-1)) significantly attenuated bone loss, increased trabecular bone
      volume fraction and trabecular thickness, and significantly decreased trabecular
      pattern factor. CONCLUSION: AO-GS treatments caused moderate oestrogenic activity
      in OVX rats compared to those treated with oestradiol, suggesting the potential
      for the use of AO-GS in the treatment of menopausal symptoms and in osteoporosis
      caused by oestrogen deficiency.

PMID- 25777818
TI  - Significance of the hyperautofluorescent ring associated with choroidal
      neovascularisation in eyes undergoing anti-VEGF therapy for wet age-related
      macular degeneration.
AB  - AIM: To characterise the presence of a hyperautofluorescent (HAF) ring associated
      with choroidal neovascularisation (CNV) complex in patients with wet age-related
      macular degeneration (AMD). METHODS: Fundus autofluorescence images and spectral
      domain optical coherence tomography (OCT) scans from 362 eyes with wet AMD were
      reviewed. The presence and size of an HAF ring associated with the CNV complex
      was evaluated. A subgroup of 64 treatment-naive eyes with new-onset CNV was
      studied to analyse the relationship between pretreatment OCT characteristics and
      the presence of the HAF ring. RESULTS: An HAF ring was present in 38% of the
      entire cohort of eyes and in 39% of treatment-naive eyes. The presence of the HAF
      ring was significantly correlated with the extent of baseline subretinal fluid
      (SRF) on OCT (p=0.0113), the number of antivascular endothelial growth factor
      (VEGF) injections (p=0.0439) and the number of treatment cycles (p=0.0154). Eyes
      with an HAF ring were more likely to have disruption of the ellipsoid zone line
      once the SRF was resolved compared with eyes without an HAF ring (p=0.0002). In
      multivariate analysis, the best predictors for HAF ring were the baseline area of
      SRF (p=0.0449) and the number of anti-VEGF treatments received (p=0.0568).
      CONCLUSIONS: Nearly 40% of wet AMD eyes had an HAF ring. In treatment-naive eyes,
      the HAF ring had a significant association with SRF and was found as early as the
      baseline measurement and as long as 18 months after beginning treatment,
      persisting for up to 6 years after the initial diagnosis. Its association with
      baseline SRF and disruption of the ellipsoid zone line of the photoreceptors on
      OCT could indicate continuous stress on the outer retinal structures after
      exposure to prolonged SRF and/or transmitted autofluorescence from loss of the
      photoreceptors overlying the retinal pigment epithelium.

PMID- 25777820
TI  - Male solitary drinking and hazardous alcohol use in nine countries of the former
      Soviet Union.
AB  - BACKGROUND: Despite evidence that many people engage in solitary drinking and
      that it might be associated with negative consequences, to date, little research
      has focused on this form of drinking behaviour. This study examined the
      prevalence and factors associated with solitary drinking, and assessed whether it
      is linked with hazardous alcohol use among males in nine countries of the former
      Soviet Union (fSU). METHODS: Data came from a cross-sectional population-based
      survey undertaken in 2010/11 in Armenia, Azerbaijan, Belarus, Georgia,
      Kazakhstan, Kyrgyzstan, Moldova, Russia, and Ukraine. Information was obtained on
      the frequency of solitary drinking among male regular drinkers (i.e., those
      consuming alcoholic drinks at least once a month), and on problem drinking (CAGE)
      and heavy episodic drinking (HED). Logistic regression analysis was used to
      examine associations between the variables. RESULTS: The prevalence of occasional
      and frequent solitary drinking ranged from 8.4% (Georgia) to 42.4% (Azerbaijan),
      and 3.1% (Kazakhstan) to 8.2% (Armenia), respectively. Solitary drinking was
      associated with being older, divorced/widowed, living alone, having a bad/very
      bad household financial situation, lower levels of social support, and poor self
      rated health. Occasional solitary drinking was linked to problem drinking and
      HED, while frequent solitary alcohol use was related to problem drinking.
      CONCLUSIONS: Solitary drinking is relatively common among male regular drinkers
      in the fSU and is linked to older age, social and economic disadvantage, and
      hazardous alcohol use.

PMID- 25777821
TI  - Impact of the cardiac arrest mode on cardiac death donor lungs.
AB  - BACKGROUND: Donation after cardiac death (DCD) organs could alleviate the
      shortage of donor lungs. This study aimed to assess the influence on lung
      injuries of the way in which cardiac arrest was induced and to investigate the
      mechanisms leading to any differences. MATERIALS AND METHODS: Male rats were
      allocated into three groups as follows: sham (no warm ischemia), ventricular
      fibrillation (VF), and asphyxia group. Cardiac arrest was induced by either VF by
      way of a fibrillator or asphyxia caused by withdrawal of ventilation, which
      reflected uncontrolled and controlled DCD situations, respectively. The impact on
      lung flushing after 60 min of warm ischemia time was evaluated (n = 5, in each
      group). The physiological functions of the lungs in an isolated lung perfusion
      circuit were also evaluated with warm ischemia time prolonged to 150 min (n = 8,
      in each group). Messenger RNA expression levels of surfactant proteins (SPs) and
      inflammatory cytokines, pathologic findings, and high-energy phosphates of the
      lung tissues were investigated. RESULTS: In the asphyxia group, flushing and
      physiological functions in the isolated lung perfusion circuit were the most
      severely affected. Reverse transcription-polymerase chain reaction and pathologic
      findings revealed depletion of surfactant protein (SP)-C in lung tissues of the
      asphyxia group after reperfusion. The VF group was characteristic with elevated
      pulmonary vascular resistance. CONCLUSIONS: Lung injuries were mainly attributed
      to alveolar wall damage and depletion of SP in the asphyxia group, and
      perivascular area prominent edema in the VF group. DCD donor lungs were affected
      differently by the way in which cardiac arrest was induced.

PMID- 25777822
TI  - Growth factor therapy and lymph node graft for lymphedema.
AB  - BACKGROUND: Lymphedema still remains an unsolved problem. Secondary lymphedema
      often develops after cancer operations or radiation therapy, especially in breast
      cancer patients. Using a mouse model, we show here that the lymphatic network can
      be regenerated using lymphatic vascular growth factor therapy in combination with
      lymph node transfer. MATERIALS AND METHODS: We have compared the therapeutic
      effects of different vascular endothelial growth factors (VEGF-C, VEGF-D, VEGF
      C156S, and VEGF-A), in combination with lymph node transfer in mouse axilla. The
      lymphangiogenic effects of the growth factor therapy were examined at 3 mo
      postoperatively. RESULTS: VEGF therapy with VEGF-C and VEGF-D induced growth of
      new lymphatic vessels in the defect area, and VEGF-C also improved lymphatic
      vessel function compared with that of controls. VEGF-C156S induced moderate
      lymphangiogenesis, but the effect remained statistically nonsignificant.
      Prolymphangiogenic growth factors (VEGF-C, -D, and -C156S) also improved lymph
      node survival as compared with those of the VEGF-A and control group. VEGF-C,
      which activates both vascular endothelial growth factor receptor 2 and vascular
      endothelial growth factor receptor 3, gave the best therapeutic effect in this
      experimental lymphedema model. CONCLUSIONS: These results support our goal to
      treat secondary lymphedema by combining lymph node transfer with the growth
      factor therapy. VEGF-C provides the preferred alternative for growth factor
      therapy of lymphedema when compared with other VEGF-family growth factors, due to
      the superior lymphangiogenic response and minor blood vascular effects.

PMID- 25777824
TI  - More than a camera holder: teaching surgical skills to medical students.
AB  - BACKGROUND: Students often experience passive learning in their surgical
      rotations as they are delegated to holding the camera during laparoscopic cases.
      We introduced a laparoscopic skills course to medical students to provide hands
      on experience. We hypothesized that the course will improve basic laparoscopic
      skills and increase interest in a surgical career. MATERIALS AND METHODS: All
      students on the core surgery rotation attended two sessions in the surgical
      simulation laboratory lead by Department of Surgery faculty members. Surveys were
      used before and after the course to assess video game (VG) use and interest in a
      surgical career. Course effectiveness was assessed with a laparoscopic peg
      transfer exercise. RESULTS: One hundred one students participated with 82
      students documenting preinstruction and postinstruction peg transfer times. There
      was an overall improvement in median transfer times after instruction (before 63
      s [interquartile range {IQR} 46-84.5] versus after 50.5 s [IQR 39-65.2], P <
      0.001). When stratified by gender, men (n = 40) had faster median preintervention
      peg transfer times than women (n = 61; 65 s [IQR 51-88]) versus 81 s [IQR 65-98]
      (P = 0.030). However, both genders had equivalent postinstruction transfer times
      (men 48 s [IQR 36-61] versus women 51.3 s [IQR 43.2-68.3], P = 0.478). A similar
      trend was observed between students with and without prior VG use. Of the 50
      students who completed both surveys, there was no significant increase (pre-24%
      versus post-34%, P = 0.29) or decrease (pre-32% versus post-22%, P = 0.13) in
      interest in a surgical career after the course. CONCLUSIONS: A laparoscopic
      course for medical students is effective in improving laparoscopic skills.
      Although male gender and VG use may be associated with better intrinsic skills,
      instruction and practice allow female students and non-VG users to "catch up." A
      longer follow-up study is warranted to determine true interest in a surgical
      career.

PMID- 25777823
TI  - Hypothermia and valproic acid activate prosurvival pathways after hemorrhage.
AB  - BACKGROUND: Therapeutic hypothermia (hypo) and valproic acid (VPA, a histone
      deacetylase inhibitor) have independently been shown to be protective in models
      of trauma and hemorrhagic shock but require logistically challenging doses to be
      effective. Theoretically, combined treatment may further enhance effectiveness,
      allowing us to use lower doses of each modality. The aim of this study was to
      determine whether a combination of mild hypo and VPA treatments would offer
      better cytoprotection compared with that of individual treatments in a hemorrhage
      model. MATERIALS AND METHODS: Male Sprague-Dawley rats were subjected to 40%
      volume-controlled hemorrhage, kept in shock for 30 min, and assigned to one of
      the following treatment groups: normothermia (36 degrees C-37 degrees C), hypo
      (30 +/- 2 degrees C), normothermia + VPA (300 mg/kg), and hypo + VPA (n = 5 per
      group). After 3 h of observation, the animals were sacrificed, liver tissue was
      harvested and subjected to whole cell lysis, and levels of key proteins in the
      prosurvival Akt pathway were measured using Western blot. RESULTS: Activation of
      the proapoptotic protein cleaved caspase-3 was significantly lower in the
      combined treatment group relative to normothermia (P < 0.05). Levels of the
      prosurvival Bcl-2 was significantly higher in the combined treatment group
      relative to sham, normothermia, and normothermia + VPA groups (P < 0.005). The
      downstream prosurvival protein phospho-GSK-3beta was significantly higher in the
      sham, hypo, and combined treatment groups compared with that in normothermia
      groups with or without VPA (P < 0.05). Levels of the prosurvival beta-catenin
      were significantly higher in the combined treatment group relative to
      normothermia (P < 0.01). CONCLUSIONS: This is the first in vivo study to
      demonstrate that combined treatment with VPA and hypo offers better
      cytoprotection than these treatments given independently.

PMID- 25777825
TI  - Early versus late hospital readmission after pancreaticoduodenectomy.
AB  - BACKGROUND: Most studies focus on readmission within 30 d of surgery and may
      therefore underestimate the true burden of readmission after complex procedures.
      We therefore sought to explore factors associated with readmission within 90 d of
      discharge after pancreaticoduodenectomy (PD). METHODS: Patients discharged after
      PD between 2010 and 2012 were identified from the Truven Health MarketScan
      database. Determinants of early (<=30 d) and late (31-90 d) readmission were
      identified and analyzed. RESULTS: A total of 2209 patients met inclusion criteria
      with 615 patients being readmitted within 90 d; 20.37% (n = 450) had an early
      readmission, whereas 7.47% (n = 165) had a late readmission. Patients readmitted
      early had a longer length-of-stay (LOS) for the readmission compared with
      patients readmitted late (median LOS = 5 d, interquartile range, 3-8 versus
      median LOS = 3 d, interquartile range, 2-5, P < 0.001). Common causes for
      readmission differed between these two patient groups. On multivariable analysis,
      postoperative complications (odds ratio [OR] 1.46, 95% confidence interval [CI]
      1.16-1.84, P < 0.001), an extended LOS (OR 1.34, CI 1.05-1.71, P = 0.019), and
      the presence of preexisting coronary heart disease (OR 1.82, CI 1.09-3.01, P =
      0.020) or renal disease (OR 2.15, CI 1.01-4.61, P = 0.048) were associated with
      an early readmission. No patient- or procedure-related factors were associated
      with late readmission. CONCLUSIONS: Readmission within 30 d after PD was
      associated with patient- and procedure-related factors. Readmission in the 31-90
      d window was not associated with patient- or procedure-related factors and may be
      influenced by the underlying pathology or subsequent medical management for that
      disease.

PMID- 25777827
TI  - The linkage of global stroke organizations.

PMID- 25777826
TI  - Shock releases bile acid inducing platelet inhibition and fibrinolysis.
AB  - BACKGROUND: Metabolites are underappreciated for their effect on coagulation.
      Taurocholic acid (TUCA), a bile acid, has been shown to regulate cellular
      activity and promote fibrin sealant degradation. We hypothesize that TUCA impairs
      whole blood clot formation and promotes fibrinolysis. METHODS: TUCA was
      exogenously added to whole blood obtained from volunteers. A titration from 250
      MUM-750 MUM was used due to biologic relevance. Whole blood mixtures were assayed
      using thrombelastography for clot strength (maximum amplitude [MA]) and
      fibrinolysis (LY30) quantification. Tranexamic acid was used to block plasmin
      mediated fibrinolysis. Platelet microfluidics were performed. A proteomic
      analysis was completed on citrated plasma obtained from a shock and resuscitation
      rat model. RESULTS: Fibrinolysis increased when 750-MUM TUCA was added to whole
      blood (median LY30 0.08-5.7, P = 0.010) and clot strength decreased (median MA of
      53.3-43.8, P = 0.010). The addition of tranexamic acid, to a 750-MUM TUCA
      titration, partially reversed the induced fibrinolysis (LY30: without 7.7 versus
      with 2.7) and the decrease in clot strength (MA: without 48.2 versus with 53.2),
      but did not reverse the effects to whole blood levels. Platelet function reduced
      by 50% in the presence of 100-MUM TUCA. Rats had a median 52-fold increase in
      TUCA, after a shock state that stayed elevated after resuscitation. CONCLUSIONS:
      TUCA reduces clot strength and promotes fibrinolysis. The clot strength reduction
      is attributable to platelet inhibition. This metabolic effect on coagulation
      warrants further investigation, as localized areas of the body, with high levels
      of bile acid, may be at risk for postoperative bleeding.

PMID- 25777828
TI  - Striving for excellence: stroke guidelines are a crucial foundation.

PMID- 25777829
TI  - Endovascular stroke therapy--a new era.

PMID- 25777830
TI  - Fatigue after stroke--perspectives and future directions.
AB  - Fatigue is a common consequence of stroke and adversely affects long-term
      outcomes. It is associated with a number of psychological and biological factors.
      Nevertheless, its mechanisms are not well understood. There may be subtypes of
      post-stroke fatigue e.g. primary and secondary, subjective fatigue and activity
      dependent fatigability--but further research is needed to determine whether such
      subtypes exist. There is very limited evidence for treatment of fatigue after
      stroke. Psychosocial treatments and physical activity are promising method for
      its management. Other potentially effective treatment options include mind-body
      interventions, and use of psychostimulants. More research is needed in this area.

PMID- 25777832
TI  - Functional health literacy is significantly associated with risk factors for
      stroke in a population sample.

PMID- 25777833
TI  - Practice diversity among US stroke physicians with respect to the 3- to 4.5-h
      window.

PMID- 25777834
TI  - Stroke knowledge and screening in a high prevalence, low-income community.

PMID- 25777835
TI  - Is methylenetetrahydrofolate reductase A1298C genotype a risk factor for carotid
      artery dissection?

PMID- 25777831
TI  - SolitaireTM with the Intention for Thrombectomy as Primary Endovascular Treatment
      for Acute Ischemic Stroke (SWIFT PRIME) trial: protocol for a randomized,
      controlled, multicenter study comparing the Solitaire revascularization device
      with IV tPA with IV tPA alone in acute ischemic stroke.
AB  - RATIONALE: Early reperfusion in patients experiencing acute ischemic stroke is
      critical, especially for patients with large vessel occlusion who have poor
      prognosis without revascularization. SolitaireTM stent retriever devices have
      been shown to immediately restore vascular perfusion safely, rapidly, and
      effectively in acute ischemic stroke patients with large vessel occlusions. AIM:
      The aim of the study was to demonstrate that, among patients with large vessel,
      anterior circulation occlusion who have received intravenous tissue plasminogen
      activator, treatment with Solitaire revascularization devices reduces degree of
      disability 3 months post stroke. DESIGN: The study is a global multicenter, two
      arm, prospective, randomized, open, blinded end-point trial comparing functional
      outcomes in acute ischemic stroke patients who are treated with either
      intravenous tissue plasminogen activator alone or intravenous tissue plasminogen
      activator in combination with the Solitaire device. Up to 833 patients will be
      enrolled. PROCEDURES: Patients who have received intravenous tissue plasminogen
      activator are randomized to either continue with intravenous tissue plasminogen
      activator alone or additionally proceed to neurothrombectomy using the Solitaire
      device within six-hours of symptom onset. STUDY OUTCOMES: The primary end-point
      is 90-day global disability, assessed with the modified Rankin Scale (mRS).
      Secondary outcomes include mortality at 90 days, functional independence (mRS <=
      2) at 90 days, change in National Institutes of Health Stroke Scale at 27 h,
      reperfusion at 27 h, and thrombolysis in cerebral infarction 2b/3 flow at the end
      of the procedure. ANALYSIS: Statistical analysis will be conducted using
      simultaneous success criteria on the overall distribution of modified Rankin
      Scale (Rankin shift) and proportions of subjects achieving functional
      independence (mRS 0-2).

PMID- 25777836
TI  - A biochemical view: plasma free fatty acids and risk of stroke in the
      cardiovascular health study.

PMID- 25777837
TI  - Safety of intravenous thrombolysis for acute ischemic stroke in patients with
      preexisting intracranial neoplasms: a case series.

PMID- 25777838
TI  - 7Tesla vessel wall imaging of the basilar artery in perimesencephalic hemorrhage.

PMID- 25777839
TI  - Evaluation of the ToxRTool's ability to rate the reliability of toxicological
      data for human health hazard assessments.
AB  - Regulatory agencies often utilize results from peer reviewed publications for
      hazard assessments. A problem in doing so is the lack of well-accepted tools to
      objectively, efficiently and systematically assess the quality of published
      toxicological studies. Herein, we evaluated the publicly available software-based
      ToxRTool (Toxicological data Reliability assessment Tool) for use in human health
      hazard assessments. The ToxRTool was developed by the European Commission's Joint
      Research Center in 2009. It builds on Klimisch categories, a rating system
      established in 1997, by providing additional criteria and guidance for assessing
      the reliability of toxicological studies. It also transparently documents the
      study-selection process. Eight scientists used the ToxRTool to rate the same 20
      journal articles on thyroid toxicants. Results were then compared using the Finn
      coefficient and "AC1" to determine inter-rater consistency. Ratings were most
      consistent for high-quality journal articles, but less consistent as study
      quality decreased. Primary reasons for inconsistencies were that some criteria
      were subjective and some were not clearly described. It was concluded, however,
      that the ToxRTool has potential and, with refinement, could provide a more
      objective approach for screening published toxicology studies for use in health
      risk evaluations, although the ToxRTool ratings are primarily based on study
      reporting quality. 

PMID- 25777840
TI  - A longitudinal study of smokers' exposure to cigarette smoke and the effects of
      spontaneous product switching.
AB  - A challenge in investigating the effect of public health policies on cigarette
      consumption and exposure arises from variation in a smoker's exposure from
      cigarette to cigarette and the considerable differences between smokers. In
      addition, limited data are available on the effects of spontaneous product
      switching on a smoker's cigarette consumption and exposure to smoke constituents.
      Over 1000 adult smokers of the same commercial 10mg International Organization
      for Standardization (ISO) tar yield cigarette were recruited into the non
      residential, longitudinal study across 10 cities in Germany. Cigarette
      consumption, mouth level exposure to tar and nicotine and biomarkers of exposure
      to nicotine and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone were measured
      every 6months over a 3 and a half year period. Cigarette consumption remained
      stable through the study period and did not vary significantly when smokers
      spontaneously switched products. Mouth level exposure decreased for smokers
      (n=111) who switched to cigarettes of 7mg ISO tar yield or lower. In addition,
      downward trends in mouth level exposure estimates were observed for smokers who
      did not switch cigarettes. Data from this study illustrate some of the challenges
      in measuring smokers' long-term exposure to smoke constituents in their everyday
      environment. 

PMID- 25777934
TI  - A fantastic voyage for sliding bacteria.
AB  - A recent study showed that Salmonella enterica serovar Typhimurium exhibits
      sliding motility under magnesium-limited conditions. Overall, bacteria that
      exhibit this passive surface movement described as sliding share few common
      traits. This discovery provides an opportunity to revisit and better characterize
      appendage-independent bacterial motility. 

PMID- 25777935
TI  - Alterations of testosterone metabolism in microsomes from rats with experimental
      colitis induced by dextran sulfate sodium.
AB  - Down-regulation of some hepatic cytochrome P450s (CYP450s) was observed in
      patients and animals with ulcerative colitis (UC). This study examined changes of
      CYP450s activities in microsomes of liver (RLMs), intestine (RIMs) and kidney
      (RRMs) from rats with experimental acute colitis induced by 5% dextran sulfate
      sodium (DSS) for 7days and those receiving DSS treatment followed by 7-d
      cessation through measuring 6alpha-(CYP1A1), 7alpha-(CYP2A1), 16alpha-(CYP2C11)
      and 2beta-/6beta-(CYP3A2) hydroxytestosterone (OHT) formed from testosterone.
      Both pro-(IL-1beta, IL-6, TNF-alpha) and anti-(IL-4, IL-10) inflammatory
      cytokines were elevated in acute colitis, while the production of the former was
      enhanced and that of the latter declined by DSS withdrawal. In RLMs, the CYP2A1
      activity was significantly increased at DSS stimulation and partially returned to
      normal level when DSS treatment was terminated. Activity of other CYP450s were
      decreased by acute colitis and remained after DSS withdrawal. In RRMs, formations
      of 6alpha-, 16alpha- and 2beta-OHT significantly declined in acute colitis and
      DSS termination further potentiated the down-regulation, while 7alpha-OHT
      formation was suppressed at DSS stimulation and remained after DSS withdrawal.
      The formation of 6beta-OHT only showed significant decrease after DSS withdrawal.
      Two metabolites (6alpha- and 6beta-OHT) formed in RIMs and 6beta-OHT formation
      was significantly decreased by DSS stimulation and continued after DSS treatment
      halted. These findings indicate that the alterations of CYP450s activities vary
      with organ, CYP isoforms and colitis status, which arouse cautions on efficacy
      and toxicity of drug therapy during disease progression. 

PMID- 25777936
TI  - Current data on the background burden to the persistent organochlorine pollutants
      HCB, p,p'-DDE as well as PCB 138, PCB 153 and PCB 180 in plasma of the general
      population in Germany.
AB  - Despite their long-term ban, persistent organochlorine compounds like
      hexachlorobenzene (HCB), p,p'-dichlorodiphenylethylene (DDE) as well as
      polychlorinated biphenyls (PCBs) are still of environmental concern. For the
      evaluation of potential occupational or environmental exposures to these
      substances, it is essential to know the current background burden of the general
      population. As representative and up-to-date information is missing for Germany,
      we have analysed a large dataset generated in studies on potential exposure to
      lower chlorinated PCBs to fill this gap for the levels of HCB, DDE as well as PCB
      138, PCB 153 and PCB 180. We have investigated n=2750 plasma samples of persons
      of the general population living in North Rhine-Westfalia and Hesse aged 6-65
      years and sampled between September 2010 and March 2014. For evaluation of the
      age-dependent accumulation in the general population we have generated seven age
      groups in the collective. Our laboratory used a validated and quality controlled
      procedure using GC/MS for quantification of the organochlorine compounds in
      plasma (LOQ: 0.01MUg/L). The median (95th percentile) levels for ? PCB 138+PCB
      153+PCB 180 were 0.14 (0.73); 0.30 (0.82); 0.38 (0.88); 0.50 (1.14); 0.92; 1.58
      (3.54) and 2.41 (4.82)MUg/L plasma in the age groups 6-10 years (n=102), 11-17
      years (n=499), 18-25 years (n=157), 26-35 years (n=710), 36-45 years (n=400), 46
      55 years (n=525) and 56-65 years (n=357), respectively. Similarly, the median
      (95th percentile) levels of p,p'-DDE were 0.18 (1.24); 0.18 (0.74); 0.24 (0.85);
      0.30 (1.20); 0.45 (1.74); 0.64 (3.25) and 0.94 (4.7)MUg/L plasma. Finally, the
      median (95th percentile) of HCB in plasma in these age groups was 0.05 (0.10);
      0.06 (0.11); 0.08 (0.15); 0.08 (0.15); 0.11 (0.22); 0.14 (0.42) and 0.20
      (0.68)MUg/L plasma. Our results prove an overall substantial reduction in the
      body burden to organochlorine compounds in Germany compared to earlier studies.
      However, 15% and 3.6% of the examined collective exceeded the HBM-I- and HBM-II
      values for PCBs established by the German Human Biomonitoring Commission. Due to
      a large sample size and a collection period from 2010 to 2014, our data might be
      suitable for the evaluation of additional exposures to these POPs and may serve
      as reference values. 

PMID- 25777937
TI  - Incidence, prevalence and 1-year all-cause mortality of heart failure in Germany:
      a study based on electronic healthcare data of more than six million persons.
AB  - AIMS: Heart failure (HF) continues to be a leading cause of morbidity and
      mortality in industrialized countries. Data on the epidemiology of HF are largely
      lacking for Germany. The aims of this study were to estimate the incidence and
      prevalence of HF in Germany, to estimate 1-year all-cause mortality in patients
      who received their first diagnosis of HF in hospital and to assess related risk
      factors. METHODS: The study was based on data for the years 2004-2006 from three
      German statutory health insurance providers, comprising data of more than six
      million people. The study sample was not restricted to a specific age group. The
      incidence rate of HF in 2006 was assessed in patients who did not have a
      diagnosis of HF or had not received medications for HF in the previous 2 years.
      One-year all-cause mortality in patients who received their first diagnosis of HF
      in hospital was analysed using Kaplan-Meier method and Cox proportional hazard
      model. Case identification was based on confirmed outpatient diagnoses, main and
      secondary hospital discharge diagnoses as well as medications for HF. RESULTS:
      The age- and sex-standardized incidence rate of HF was 2.7 per 1000 person years.
      Age- and sex-standardized prevalence of HF was 1.7% in 2004, 1.9% in 2005 and
      1.7% in 2006. The 1-year all-cause mortality was 23% among patients who received
      their first HF diagnosis during a hospitalization in 2006. CONCLUSION: Our study
      revealed an incidence and prevalence of HF in Germany which were largely
      comparable to those from other countries. Due to the poor prognosis of HF, high
      readmission rates and an aging society, HF remains highly relevant in the context
      of health care planning.

PMID- 25777938
TI  - Partial right atrial standstill enhancing SVC re-entry tachycardia.

PMID- 25777939
TI  - In vitro evidence that sulfite impairs glutamatergic neurotransmission and
      inhibits glutathione metabolism-related enzymes in rat cerebral cortex.
AB  - Sulfite oxidase (SOX) deficiency is an inherited neurometabolic disorder
      biochemically characterized by tissue accumulation and high urinary excretion of
      sulfite and thiosulfate. Affected patients present severe neurological
      dysfunction accompanied by seizures, whose pathophysiology is poorly known. In
      the present study we evaluated the in vitro effects of sulfite and thiosulfate on
      important parameters of glutamatergic neurotransmission and redox homeostasis in
      rat cerebral cortex slices. We verified that sulfite, but not thiosulfate,
      significantly decreased glutamate uptake when cerebral cortex slices were exposed
      during 1h to these metabolites. We also observed that thiosulfate inhibited
      glutamine synthetase (GS) activity. A pronounced trend toward GS inhibition
      induced by sulfite was also found. Regarding redox homeostasis, sulfite, at the
      concentration of 10 MUM, increased thiobarbituric acid-reactive substances and
      decreased glutathione concentrations after 1h of exposure. In contrast,
      thiosulfate did not alter these parameters. We also found that 500 MUM sulfite
      increased sulfhydryl group content in rat cerebral cortex slices and increased
      GSH levels in a medium containing oxidized GSH (GSSG) and devoid of cortical
      slices, suggesting that sulfite reacts with disulfide bonds to generate
      sulfhydryl groups. Moreover, sulfite and thiosulfate did not alter the activities
      of glutathione peroxidase (GPx), glutathione reductase (GR), glutathione S
      transferase (GST) and glucose-6-phosphate dehydrogenase (G6PDH) after 1h of
      incubation. However, sulfite inhibited the activities of GPx, GST and G6PDH when
      cortical slices were exposed for 3h to sulfite. We finally verified that sulfite
      did not induce cell death after 1h of incubation. Our data show that sulfite
      impairs glutamatergic neurotransmission and redox homeostasis in cerebral cortex.
      Therefore, it may be presumed that these pathomechanisms contribute, at least in
      part, to the seizures observed in patients affected by SOX deficiency.

PMID- 25777940
TI  - Ischemic postconditioning in cerebral ischemia: Differences between the immature
      and mature brain?
AB  - Ischemic postconditioning (postC), defined as serial mechanical interruptions of
      blood flow at reperfusion, effectively reduces myocardial infarct size in all
      species tested so far, including humans. In the brain, ischemic postC leads to
      controversial results regardless of variations in factors such as onset time of
      beginning, the duration of ischemia and/or reperfusion, and the number of cycles
      of occlusion/reperfusion. Thus, many major issues remain to be resolved regarding
      its protective effects. Future studies should aim to identify the parameters that
      yield the strongest protection, as well as to understand why the efficacy of
      ischemic postC differs between models. This review will focus on initial
      hemodynamic changes and their consequences, and on specific features such as NO
      dependent vascular tone and/or prolonged acidosis in cerebral ischemia
      reperfusion in order to better understand the dynamics of ischemic postC in the
      developing brain. 

PMID- 25777941
TI  - Variation among Bm86 sequences in Rhipicephalus (Boophilus) microplus ticks
      collected from cattle across Thailand.
AB  - Anti-tick vaccines based on recombinant homologues Bm86 and Bm95 have become a
      more cost-effective and sustainable alternative to chemical pesticides commonly
      used to control the cattle tick, Rhipicephalus (Boophilus) microplus. However,
      Bm86 polymorphism among geographically separate ticks is reportedly associated
      with reduced effectiveness of these vaccines. The purpose of this study was to
      investigate the variation of Bm86 among cattle ticks collected from Northern,
      Northeastern, Central and Southern areas across Thailand. Bm86 cDNA and deduced
      amino acid sequences representing 29 female tick midgut samples were 95.6-97.0
      and 91.5-93.5 % identical to the nucleotide and amino acid reference sequences,
      respectively, of the Australian Yeerongpilly vaccine strain. Multiple sequence
      analyses of these Bm86 variants indicated geographical relationships and
      polymorphism among Thai cattle ticks. Two larger groups of cattle tick strains
      were discernable based on this phylogenetic analysis of Bm86, a Thai group and a
      Latin American group. Thai female and male cattle ticks (50 pairs) were also
      subjected to detailed morphological characterization to confirm their identity.
      The majority of female ticks had morphological features consistent with those
      described for R. (B.) microplus, whereas, curiously, the majority of male ticks
      were more consistent with the recently re-instated R. (B.) australis. A number of
      these ticks had features consistent with both species. Further investigations are
      warranted to test the efficacies of rBm86-based vaccines to homologous and
      heterologous challenge infestations with Thai tick strains and for in-depth study
      of the phylogeny of Thai cattle ticks. 

PMID- 25777942
TI  - A novel protein, Rsf1/Pxd1, is critical for the single-strand annealing pathway
      of double-strand break repair in Schizosaccharomyces pombe.
AB  - The process of single-strand annealing (SSA) repairs DNA double-strand breaks
      that are flanked by direct repeat sequences through the coordinated actions of a
      series of proteins implicated in recombination, mismatch repair and nucleotide
      excision repair (NER). Many of the molecular and mechanistic insights gained in
      SSA repair have principally come from studies in the budding yeast Saccharomyces
      cerevisiae. However, there is little molecular understanding of the SSA pathway
      in the fission yeast Schizosaccharomyces pombe. To further our understanding of
      this important process, we established a new chromosome-based SSA assay in
      fission yeast. Our genetic analyses showed that, although many homologous
      components participate in SSA repair in these species indicating that some
      evolutionary conservation, Saw1 and Slx4 are not principal agents in the SSA
      repair pathway in fission yeast. This is in marked contrast to the function of
      Saw1 and Slx4 in budding yeast. Additionally, a novel genus-specific protein,
      Rsf1/Pxd1, physically interacts with Rad16, Swi10 and Saw1 in vitro and in vivo.
      We find that Rsf1/Pxd1 is not required for NER and demonstrate that, in fission
      yeast, Rsf1/Pxd1, but not Saw1, plays a critical role in SSA recombination. 

PMID- 25777943
TI  - Similarities and differences in adolescence-onset versus adulthood-onset sexual
      abuse incidents.
AB  - A sample of males who had first committed sexual offences against children in
      either adolescence (n=230; M=14.0 years, SD=1.5) or adulthood (n=280; M=34.4
      years, SD=11.7) were compared on measures relating to the circumstances of their
      first known sexual abuse incident. Considerable diversity in the circumstances of
      these first incidents was observed for both groups. However, adulthood-onset
      sexual abuse most often occurred following a long-standing familial relationship
      with a female victim, and in a home setting. The first incident for adolescence
      onset offenders also tended to occur in the context of a long-term relationship
      and against a female child in a home setting, but more commonly against a
      nonfamilial victim. Adulthood-onset offenders abused older children, were more
      likely to engage in penetrative sexual behaviors, and went on to abuse over a
      longer duration than adolescence-onset offenders. Adolescence-onset offences were
      more likely to be witnessed by a third party. Findings and their implications for
      prevention are considered from a situational crime prevention perspective. 

PMID- 25777944
TI  - [Dignity of the elderly].
AB  - A discussion is presented on what is understood by "dignity" when applied to the
      elderly, highlighting it universal character and contrasting it with the greater
      risks of suffering "indignities" to which the elderly are exposed. The discussion
      is divided into 3 sections. In the first, the risk factors in this sense could
      lead to physiological losses and illnessess, which in in the physical, mental and
      social sense are associated with ageing. In the second, the question of
      discrimination of the elderly as a form of aggression due to age, and is so
      widespread and infrequently studied. Lastly, it is discussed how to interpret the
      advice of the United Nations on how to promote active ageing as a defence system
      against indignities. It concludes with the message that neither the limitations
      that accompany the ageing process, nor the different forms of aggression that the
      elderly may be subjected to, provide sufficient argument neither for a loss of
      individual nor collective dignity. This is something which we all must endeavour
      to achieve and which must be maintained and be respected by individuals and by
      society at all times. 

PMID- 25777945
TI  - [Randomized clinical trial of a fall-prevention strategy for institutionalized
      elderly based on the Mini Falls Assessment Instrument].
AB  - INTRODUCTION: The Mini Falls Assessment Instrument (MFAI) identifies risk factors
      for falls in an individual and links them to specific interventions. This study
      evaluates the effectiveness of MFAI as the basis for a falls prevention strategy
      in institutionalized elderly. MATERIAL AND METHODS: A cluster randomized clinical
      trial (identifier NCT00888953) was conducted in 16 nursing homes randomized to
      apply MFAI (intervention) or a modified version not linked to actions (control).
      The primary endpoint was the occurrence of falls during follow-up (12 months).
      Secondary variables were total number of falls, physical function, quality of
      life, functional status, and adverse effects. RESULTS: Data from 330 participants
      (197 intervention, 137 control) were analyzed. Both groups had a similar number
      of risk factors: 7 in the intervention group (range 1-12) and 8 (1-13) in the
      control group. In the intervention group there were more fallers (49% vs. 38%),
      and higher number of falls (315 vs. 109), and fall rate per 100 person-years
      (192.5 vs. 179.8) than the control group. In the multivariate analysis, there
      were no significant differences in fall risk (odds ratio=1.45; 95% confidence
      interval [CI]: .67 to 3.14; P=.350), but the incidence rate is significantly
      higher in the intervention group (Incidence rate ratio=2.23; 95% CI: 1.43 to
      3.48; P<.001). CONCLUSIONS: The results on the efficacy of the MFAI as a fall
      prevention strategy are inconclusive. Additional studies are needed in order to
      provide good quality evidence.

PMID- 25777946
TI  - [Update on oncological pain in the elderly].
AB  - Pain is a prevalent symptom in cancer geriatric patients, appearing in up to 90%
      of patients with terminal cancer. This requires a multidimensional approach, as
      there is a high percentage of inappropriate assessments and treatments.
      Unrecognized or poorly treated pain in the geriatric population, especially in
      cancer patients, leads to the development of disabling symptoms such as
      depression, anxiety, isolation, sleep disturbances, and appetite, and very
      especially, loss of functional capacity and quality of life. In this review an
      analysis is made on the most relevant studies on the diagnosis and management of
      cancer pain in the geriatric population. 

PMID- 25777947
TI  - Stereospecific 7alpha-alkylation of 20-hydroxyecdysone in a lithium-ammonia
      solution.
AB  - The reaction of 20-hydroxyecdysone with methyl or ethyl iodide or allyl bromide
      in a lithium-ammonia solution results in stereospecific 7alpha-alkylation to give
      7alpha-methyl-, 7alpha-ethyl-, and 7alpha-allyl-14-deoxy-Delta(8(14))-20
      hydroxyecdysones, respectively. By catalytic hydrogenation (Pd-C/MeOH), the
      7alpha-allyl derivative was converted to 7alpha-n-propyl-14-deoxy-Delta(8(14))-20
      hydroxyecdysone. 

PMID- 25777948
TI  - Synthesis, spectroscopy, theoretical and biological studies of new gramine
      steroids salts and conjugates.
AB  - New gramine connections with bile acids (lithocholic, deoxycholic, cholic) and
      sterols (cholesterol, cholestanol) were synthesized. The structures of products
      were confirmed by spectral (NMR, FT-IR) analysis, mass spectrometry (ESI-MS) as
      well as PM5 semiempirical methods. Unexpectedly, the products of the reaction of
      gramine with cholesterol and cholestanol were symmetrical compounds consisting of
      two molecules of sterols connected by N(CH3)2 group. All new synthesized
      compounds interact in vitro with the human erythrocyte membrane and alter discoid
      erythrocyte shape inducing stomatocytosis or echinocytosis. Increase in the
      incorporation of the fluorescent dye merocyanine 540 (MC540) into the erythrocyte
      membrane indicates that new compounds at sublytic concentrations are capable of
      disturbing membrane phospholipids asymmetry and loosening the molecular packing
      of phospholipids in the bilayer. Gramine significantly decreases the membrane
      partitioning properties as well as haemolytic activity of lithocholic acid in its
      new salt. Moreover, both deoxycholic and cholic acids completely lost their
      membrane perturbing activities in the gramine salts. On the other hand, the
      capacity of new gramine-sterols connections to alter the erythrocyte membrane
      structure and its permeability is much higher in comparison with sterols alone.
      The dual effect of gramine on the bile acid and sterols cell membrane
      partitioning activity observed in our study should not be neglected in vivo. 

PMID- 25777949
TI  - Process variability of pollutant build-up on urban road surfaces.
AB  - Knowledge of the pollutant build-up process is a key requirement for developing
      stormwater pollution mitigation strategies. In this context, process variability
      is a concept which needs to be understood in-depth. Analysis of particulate build
      up on three road surfaces in an urban catchment confirmed that particles <150 MUm
      and >150 MUm have characteristically different build-up patterns, and these
      patterns are consistent over different field conditions. Three theoretical build
      up patterns were developed based on the size-fractionated particulate build-up
      patterns, and these patterns explain the variability in particle behavior and the
      variation in particle-bound pollutant load and composition over the antecedent
      dry period. Behavioral variability of particles <150 MUm was found to exert the
      most significant influence on the build-up process variability. As
      characterization of process variability is particularly important in stormwater
      quality modeling, it is recommended that the influence of behavioral variability
      of particles <150 MUm on pollutant build-up should be specifically addressed.
      This would eliminate model deficiencies in the replication of the build-up
      process and facilitate the accounting of the inherent process uncertainty, and
      thereby enhance the water quality predictions.

PMID- 25777950
TI  - Prevalence of enteropathogenic bacteria in treated effluents and receiving water
      bodies and their potential health risks.
AB  - The failure of wastewater treatment plants to produce effluents of a high
      microbiological quality is a matter of great concern in terms of water resource
      pollution. A more serious concern is that this water source is used by
      communities in developing countries for multiple purposes, which include
      drinking, recreation and agriculture. The current study investigated the
      prevalence and potential health risks of enteropathogenic bacteria (Salmonella
      typhimurium, Shigella dysenteriae and Vibrio cholerae) in the treated effluents
      of three selected South African Wastewater Treatment Works as well as their
      receiving water bodies. Culture-based and polymerase chain reaction techniques
      were used to detect and identify the pathogenic bacteria. The conventional
      methods revealed that of the 272 water samples collected, 236 samples (86.8%)
      tested presumptively positive for Salmonella spp., 220 samples (80.9%) for
      Shigella spp. and 253 samples (93.0%) for V. cholerae. Molecular test results
      indicated that out of the randomly selected presumptive positive samples (145),
      zero to 60% of samples were positive for S. typhimurium and S. dysenteriae and
      20% to 60% for V. cholerae. For the health risk assessment, the daily combined
      risk of S. typhimurium, S. dysenteriae and V. cholerae infection was above the
      lowest acceptable risk limit of 10(-4) as estimated by the World Health
      Organization for drinking water. This study showed that the target treated
      wastewater effluents and their receiving water bodies could pose a potential
      health risk to the surrounding communities. 

PMID- 25777951
TI  - Diuron, Irgarol 1051 and Fenitrothion contamination for a river passing through
      an agricultural and urban area in Higashi Hiroshima City, Japan.
AB  - A study was conducted on the pesticides Diuron, Irgarol 1051 and Fenitrothion in
      Kurose River water, Higashi Hiroshima, Japan for a period of one year to assess
      the contribution of agriculture and urban activities on pesticide pollution of
      the river. Samples were analysed by a reverse phase HPLC system. The maximum
      pesticide concentrations were; 4620 ng/L, 50 ng/L and 370 ng/L for Diuron,
      Irgarol 1051 and Fenitrothion, respectively. While Diuron and Fenitrothion were
      detected at all sites, Irgarol 1051 was only present at Izumi, a high density
      urban and industrial area which also registered the highest concentrations of the
      pesticides. The pattern showed by Diuron and Fenitrothion was linked to farming
      activities. Also, Diuron and Fenitrothion concentration correlated with pesticide
      utilization data for Hiroshima Prefecture. Irgarol 1051 showed a different
      pattern to that of Diuron and Fenitrothion and its source was attributed to
      paint. It was noted that 78% and 42% of water samples at Izumi sampling site
      exceeded the European Union (EU) guidelines for Diuron and Fenitrothion,
      respectively.

PMID- 25777952
TI  - Characterization of Pharmaceuticals and Personal Care products in hospital
      effluent and waste water influent/effluent by direct-injection LC-MS-MS.
AB  - Two USEPA Regional Laboratories developed direct-injection LC/MS/MS methods to
      measure Pharmaceuticals and Personal Care Products (PPCPs) in water matrices.
      Combined, the laboratories were prepared to analyze 185 PPCPs (with 74
      overlapping) belonging to more than 20 therapeutical categories with reporting
      limits at low part-per-trillion. In partnership with Suffolk County in NY, the
      laboratories conducted PPCP analysis on 72 samples belonging to 4 Water Systems
      (WS). Samples were collected at different stages of the WS (hospital effluents,
      WWTP influents/effluents) to assess PPCP relevance in hospital discharges, impact
      on WWTP performance and potential ecological risk posed by analytes not
      eliminated during treatment. Major findings include: a) acceptable accuracy
      between the two laboratories for most overlapping PPCPs with better agreement for
      higher concentrations; b) the measurement of PPCPs throughout all investigated WS
      with total PPCP concentrations ranging between 324 and 965 MUg L(-1) for hospital
      effluent, 259 and 573 MUg L(-1) for WWTP influent and 19 and 118 MUg L(-1) for
      WWTP effluent; c) the variable contribution of hospital effluents to the PPCP
      loads into the WWTP influents (contribution ranging between 1% (WS-2) and 59% (WS
      3); d) the PPCP load reduction after treatment for all WS reaching more than 95%
      for WS using activated sludge processes (WS-2 and WS-4), with inflow above 6500
      m(3) d(-1), and having a lower percentage of hospital effluent in the WWTP
      influent; e) the relevance of four therapeutical categories for the PPCP load in
      WWTP effluents (analgesics, antidiabetics, antiepileptics and psychoanaleptics);
      and f) the risk quotients calculated using screening-level Predicted Non Effect
      Concentration indicate that WWTP effluents contain 33 PPCPs with potential medium
      to high ecological risk. To our knowledge no other monitoring investigation
      published in the scientific literature uses direct-injection methods to cover as
      many PPCPs and therapeutical categories in different types of WS.

PMID- 25777953
TI  - Fate of trace organics in a wastewater effluent dependent stream.
AB  - Trace organic compounds (TOrCs) in municipal wastewater effluents that are
      discharged to streams are of potential concern to ecosystem and human health.
      This study examined the fate of a suite of TOrCs and estrogenic activity in water
      and sediments in an effluent-dependent stream in Tucson, Arizona. Sampling
      campaigns were performed during 2011 to 2013 along the Lower Santa Cruz River,
      where TOrCs and estrogenic activity were measured in aqueous (surface) and solid
      (riverbed sediment) phases. Some TOrCs, including contributors to estrogenic
      activity, were rapidly attenuated with distance of travel in the river. Those
      TOrCs that are not sufficiently attenuated and percolate to ground water have in
      common low biodegradation probabilities and low octanol-water distribution
      ratios. Independent experiments showed that attenuation of estrogenic compounds
      may be due in part to indirect photolysis caused by formation of organic radicals
      from sunlight absorption. Hydrophobic TOrCs may accumulate in riverbed sediments
      during dry weather periods, but riverbed sediment quality is periodically
      affected through storm-related scouring during periods of heavy rainfall and
      runoff. Taken together, evidence suggests that natural processes can attenuate at
      least some TOrCs, reducing potential impacts to ecosystem and human health. 

PMID- 25777954
TI  - Use of industrial by-products and natural media to adsorb nutrients, metals and
      organic carbon from drinking water.
AB  - Filtration technology is well established in the water sector but is limited by
      inability to remove targeted contaminants, found in surface and groundwater,
      which can be damaging to human health. This study optimises the design of filters
      by examining the efficacy of seven media (fly ash, bottom ash, Bayer residue,
      granular blast furnace slag (GBS), pyritic fill, granular activated carbon (GAC)
      and zeolite), to adsorb nitrate, ammonium, total organic carbon (TOC), aluminium,
      copper (Cu) and phosphorus. Each medium and contaminant was modelled to a
      Langmuir, Freundlich or Temkin adsorption isotherm, and the impact of pH and
      temperature (ranging from 10  degrees C to 29  degrees C) on their performance
      was quantified. As retention time within water filters is important in
      contaminant removal, kinetic studies were carried out to observe the adsorption
      behaviour over a 24h period. Fly ash and Bayer residue had good TOC, nutrient and
      Cu adsorption capacity. Granular blast furnace slag and pyritic fill, previously
      un-investigated in water treatment, showed adsorption potential for all
      contaminants. In general, pH or temperature adjustment was not necessary to
      achieve effective adsorption. Kinetic studies showed that at least 60% of
      adsorption had occurred after 8h for all media. These media show potential for
      use in a multifunctional water treatment unit for the targeted treatment of
      specific contaminants.

PMID- 25777955
TI  - Occurrences and regional distributions of 20 antibiotics in water bodies during
      groundwater recharge.
AB  - To develop a better understanding of the pollution conditions of antibiotics
      during the groundwater recharge process, a nation-wide survey was conducted
      across China for the first time. Overall, 15 recharge sites employing reclaimed
      water located in different humid, semi-humid and semi-arid regions were selected
      for analysis of the presence of the 20 most commonly used antibiotics, including
      tetracyclines (TCs), fluoroquinolones (FQNs), sulfonamides (SAs) and macrolides.
      All types of antibiotics were detected at concentrations of 212-4035 ng/L in
      reclaimed water and 19-1270 ng/L in groundwater. FQNs were the predominant
      antibiotics in reclaimed water samples (38%), followed by SAs (34%). In the SAs
      group, sulfamethoxazole (SMZ) and sulfamonomethoxine together with trimethoprim
      accounted for 78% of the total, while ofloxacin (OFL) and norfloxacin accounted
      for 90% of the FQNs, and doxycycline and oxytetracycline accounted for 82% of the
      TCs. The concentrations in groundwater were generally 1-2 orders of magnitude
      lower than in reclaimed water. The three most common antibiotics were OFL,
      erythromycin (ERY) and SMZ. Similar occurrences of different group antibiotics
      might be evidence of the influence of groundwater recharge by reclaimed water.
      FQNs were predominant in northern China, while SAs were predominant in the south.
      Ecotoxicological risk assessment showed that SMZ, ERY and OFL had the top three
      hazard quotient values, indicating they should receive preferential treatment
      before recharging. Overall, these results provide a theoretical basis for
      development of a recharge standard in China.

PMID- 25777956
TI  - Metal contamination of home garden soils and cultivated vegetables in the
      province of Brescia, Italy: implications for human exposure.
AB  - BACKGROUND: For the past century, ferroalloy industries in Brescia province,
      Italy produced particulate emissions enriched in manganese (Mn), lead (Pb), zinc
      (Zn), copper (Cu), cadmium (Cd), chromium (Cr), iron (Fe), and aluminum (Al).
      This study assessed metal concentrations in soil and vegetables of regions with
      varying ferroalloy industrial activity levels. METHODS: Home gardens (n=63) were
      selected in three regions of varying ferroalloy plant activity durations in
      Brescia province. Total soil metal concentration and extractability were measured
      by X-Ray Fluorescence (XRF), aqua regia extraction, and modified Community Bureau
      of Reference (BCR) sequential extraction. Unwashed and washed spinach and turnips
      cultivated in the same gardens were analyzed for metal concentrations by flame
      atomic absorption spectrometry. RESULTS: Median soil Al, Cd, Fe, Mn, Pb, and Zn
      concentrations were significantly higher in home gardens near ferroalloy plants
      compared to reference home gardens. The BCR method yielded the most mobile soil
      fraction (the sum of extractable metals in Fractions 1 and 2) and all metal
      concentrations were higher in ferroalloy plant areas. Unwashed spinach showed
      higher metal concentrations compared to washed spinach. However, some metals in
      washed spinach were higher in the reference area likely due to history of
      agricultural product use. Over 60% of spinach samples exceeded the 2- to 4-fold
      Commission of European Communities and Codex Alimentarius Commission maximum Pb
      concentrations, and 10% of the same spinach samples exceeded 2- to 3-fold maximum
      Cd concentrations set by both organizations. Turnip metal concentrations were
      below maximum standard reference values. CONCLUSIONS: Prolonged industrial
      emissions increase median metal concentrations and most soluble fractions (BCR
      F1+F2) in home garden soils near ferroalloy plants. Areas near ferroalloy plant
      sites had spinach Cd and Pb metal concentrations several-fold above maximum
      standard references. We recommend thorough washing of vegetables to minimize
      metal exposure.

PMID- 25777957
TI  - UV filters bioaccumulation in fish from Iberian river basins.
AB  - The occurrence of eight organic UV filters (UV-Fs) was assessed in fish from four
      Iberian river basins. This group of compounds is extensively used in cosmetic
      products and other industrial goods to avoid the damaging effects of UV
      radiation, and has been found to be ubiquitous contaminants in the aquatic
      ecosystem. In particular, fish are considered by the scientific community to be
      the most feasible organism for contamination monitoring in aquatic ecosystems.
      Despite that, studies on the bioaccumulation of UV-F are scarce. In this study
      fish samples from four Iberian river basins under high anthropogenic pressure
      were analysed by liquid chromatography-tandem mass spectrometry (HPLC-MS/MS).
      Benzophenone-3 (BP3), ethylhexyl methoxycinnamate (EHMC), 4-methylbenzylidene
      camphor (4MBC) and octocrylene (OC) were the predominant pollutants in the fish
      samples, with concentrations in the range of ng/g dry weight (d.w.). The results
      indicated that most polluted area corresponded to Guadalquivir River basin, where
      maximum concentrations were found for EHMC (241.7 ng/gd.w.). Sediments from this
      river basin were also analysed. Lower values were observed in relation to fish
      for OC and EHMC, ranging from below the limits of detection to 23 ng/gd.w.
      Accumulation levels of UV-F in the fish were used to calculate biota-sediment
      accumulation factors (BSAFs). These values were always below 1, in the range of
      0.04-0.3, indicating that the target UV-Fs are excreted by fish only to some
      extent. The fact that the highest concentrations were determined in predators
      suggests that biomagnification of UV-F may take place along the freshwater food
      web.

PMID- 25777958
TI  - Hair and bone as predictors of tissular mercury concentration in the western
      Alaska red fox, Vulpes vulpes.
AB  - We evaluated if total mercury (THg) concentrations of keratin-based and bone
      based tissues can predict THg concentrations in skeletal muscle, renal medulla,
      renal cortex, and liver. The THg concentration in matched tissues of 65 red
      foxes, Vulpes vulpes, from western Alaska was determined. Hair THg concentration
      had a significant positive correlation with liver, renal medulla, renal cortex,
      and muscle. The THg concentration for males and females is moderately predictive
      of THg concentration in the renal cortex and liver for these foxes based on R(2)
      values (R(2)=0.61 and 0.63, respectively). Bone is weakly predictive of THg
      concentration in muscle (R(2)=0.40), but not a reliable tissue to predict THg
      concentration in liver (R(2)=0.24), renal cortex (R(2)=0.35), or renal medulla
      (R(2)=0.25). These results confirm the potential use of trapped animals,
      specifically foxes, as useful Arctic sentinel species to inform researchers about
      patterns in THg levels over time as industrialization of the Arctic continues. 

PMID- 25777959
TI  - Changes in chemical composition and oxidative potential of urban PM(2.5) between
      2010 and 2013 in Hungary.
AB  - A comprehensive chemical characterization and oxidative potential (OP) assessment
      of PM2.5 was carried out at an urban site of Budapest between June 2010 and May
      2013 to investigate the seasonal variability of particulate phase air pollutants
      and their oxidative activity. Chemical analyses included the determination of the
      concentration of trace elements, major water-soluble inorganic ions and
      carbonaceous fractions (total carbon, water-soluble organic carbon, organic
      carbon, elemental carbon). The OP of PM2.5 was assessed by antioxidant depletion
      using a synthetic respiratory tract lining fluid containing ascorbate, reduced
      glutathione and urate. The mean PM2.5 mass concentration (21.0 MUg m(-3)) was
      just below the 25 MUg m(-3) annual mean PM2.5 limit value set by the European
      Commission and showed a seasonal pattern with higher levels during winter. On
      average, 84% of the gravimetric mass could be reconstructed by the chemical
      measurements. Organic matter and secondary inorganic ions were the most dominant
      PM2.5 constituents contributing 40 and 29% of its mass, respectively. Changes in
      the yearly concentrations were not identified for the investigated compounds
      between 2010 and 2013. Temporal differences in both ascorbate and glutathione
      oxidation could be observed during the 3-year long sampling period; however, no
      clear seasonal trend was apparent. OP metrics were associated mainly with traffic
      related trace elements; however, other PM sources (i.e., long-range transport,
      secondary aerosol formation) could also contribute to particulate OP in Budapest.
      The weak correlation between OP metrics and PM2.5 mass concentration suggests the
      possibility of using OP as an additional metric in epidemiology.

PMID- 25777960
TI  - The bioaccessibility of soil-based mercury as determined by physiological based
      extraction tests and human biomonitoring in children.
AB  - Environmental contaminants associated with soil particles are generally less
      bioavailable than contaminants associated with other exposure media where
      chemicals are often found in more soluble forms. In vitro methods, such as
      Physiological Based Extraction Tests (PBET), can provide estimates of
      bioaccessibility for soil-based contaminants. The results of these tests can be
      used to predict exposure to contaminants from soil ingestion pathways within
      human health risk assessment (HHRA). In the current investigation, an HHRA was
      conducted to examine the risks associated with elevated concentrations of mercury
      in soils in the northern Canadian smelter community of Flin Flon, Manitoba. A
      PBET was completed for residential soils and indicated mean bioaccessibilities of
      1.2% and 3.0% for total mercury using gastric phase and gastric+intestinal phase
      methodologies, respectively. However, as many regulators only allow for the
      consideration of in vitro results for lead and arsenic in the HHRA process, in
      vitro bioaccessibility results for mercury were not utilized in the current HHRA.
      Based on the need to assume 100% bioaccessibility for inorganic mercury in soil,
      results from the HHRA indicated the need for further assessment of exposure and
      risk. A biomonitoring study was undertaken for children between 2 and 15 years of
      age in the community to examine urinary inorganic mercury concentrations.
      Overall, 375 children provided valid urine samples for analysis. Approximately
      50% of urine samples had concentrations of urinary inorganic mercury below the
      limit of detection (0.1 MUg/L), with an average creatinine adjusted concentration
      of 0.11 MUg/g. Despite high variability in mercury soil concentrations within sub
      communities, soil concentrations did not appear to influence urinary mercury
      concentrations. The results of the current investigation indicate that mercury
      bioaccessibility in residential soils in the Flin Flon area was likely limited
      and that HHRA estimates would have been better approximated through inclusion of
      the in vitro study results.

PMID- 25777961
TI  - Application of biomarkers in Epaulet grouper (Epinephelus stoliczkae) to assess
      chromium pollution in the Chabahar Bay and Gulf of Oman.
AB  - In the present study plasma levels of erythropoietin (EPO) hormone and kidney
      histological changes were assessed as biomarkers to evaluate the chromium
      pollution in Epaulet grouper (Epinephelus stoliczkae) obtained from different
      areas in Chabahar Bay and Gulf of Oman. Chemical analyses included the evaluation
      of chromium in the fish kidney tissue and sediment. The highest and lowest
      concentrations of chromium were measured in the kidney of fish and sediment
      collected from Konarak (47.53+/-1.23 and 110+/-1.4 MUg g(-1)) and the mouth of
      Chabahar Bay (3.43+/-1.31 and 13.5+/-3.23 MUg g(-1)), respectively. There was
      significant difference (P<0.05) of EPO plasma levels between Konarak, Beris and
      Ramin stations with the mouth of Chabahar Bay as the cleanest station. Reduction
      of Bowman's space, occlusion of the tubule lumen, leukocytes infiltration,
      melanomacrophage centers aggregation, nuclear vacuolation, nuclei hypertrophy of
      tubule cells, necrosis of the tubules, lifting of the tubular basement membrane
      and dilatation of glomerular capillaries were the most alterations observed in
      the kidney. The HAI values of Epaulet grouper from Konarak, Beris and Ramin
      stations were significantly higher than other stations (P<0.05). It was concluded
      that selected biomarkers as a first investigation could be useful tools to
      environmental biomonitoring programs.

PMID- 25777963
TI  - Rho Guanine Nucleotide Exchange Factor 5 Increases Lung Cancer Cell Tumorigenesis
      via MMP-2 and Cyclin D1 Upregulation.
AB  - We sought to elucidate the role of Rho guanine nucleotide exchange factor 5
      (ARHGEF5) in tumorigenesis of lung adenocarcinoma cells. ARHGEF5 protein levels
      were assessed in 91 human lung adenocarcinoma specimens, and A549 and NCI-H1650
      cells, by IHC and Western blotting. In addition, ARHGEF5 mRNA expression was
      evaluated by quantitative reverse transcriptase-PCR. Furthermore, ARHGEF5 long
      and short isoform coexpression was detected by immunofluorescence. Finally, flow
      cytometry; CCK8 and wound-healing assays; cell invasion, migration and adhesion;
      and xenografts were used to evaluate the biologic significance of ARHGEF5.
      ARHGEF5 was significantly increased in lung adenocarcinoma tissues and cell
      lines. Interestingly, ARHGEF5 levels were significantly associated with tumor
      grade and pathologic stage, but not age, gender, T stage, or lymph node
      metastasis status. ARHGEF5 knockdown by RNAi resulted in dramatically reduced
      proliferation, adhesion, invasion, and migratory capability of A549 and NCI-H1650
      cells. Likewise, protein levels of p-Src, p-Akt, and NF-kappaB were significantly
      decreased after ARHGEF5 knockdown. In parallel, increased S-phase population and
      MMP-2/cyclin D1 expression were observed in the cancer cells, which were not
      apoptotic. In addition, ARHGEF5 knockdown A549 and NCI-H1650 cells injected s.c.
      and i.v. into nude mice exhibited decreased xenograft volume and overtly reduced
      metastasis. Conversely, ARHGEF5 overexpression in A549 and NCI-H1650 cells
      increased their tumorigenicity in vitro. ARHGEF5 acts as a proto-oncogene in
      human lung adenocarcinoma cell tumorigenesis.

PMID- 25777962
TI  - MGMT Expression Predicts PARP-Mediated Resistance to Temozolomide.
AB  - Melanoma and other solid cancers are frequently resistant to chemotherapies based
      on DNA alkylating agents such as dacarbazine and temozolomide. As a consequence,
      clinical responses are generally poor. Such resistance is partly due to the
      ability of cancer cells to use a variety of DNA repair enzymes to maintain cell
      viability. Particularly, the expression of MGMT has been linked to temozolomide
      resistance, but cotargeting MGMT has proven difficult due to dose-limiting
      toxicities. Here, we show that the MGMT-mediated resistance of cancer cells is
      profoundly dependent on the DNA repair enzyme PARP. Both in vitro and in vivo, we
      observe that MGMT-positive cancer cells strongly respond to the combination of
      temozolomide and PARP inhibitors (PARPi), whereas MGMT-deficient cells do not. In
      melanoma cells, temozolomide induced an antiproliferative senescent response,
      which was greatly enhanced by PARPi in MGMT-positive cells. In summary, we
      provide compelling evidence to suggest that the stratification of patients with
      cancer upon the MGMT status would enhance the success of combination treatments
      using temozolomide and PARPi.

PMID- 25777964
TI  - Synthetic Lethal Screens Identify Vulnerabilities in GPCR Signaling and
      Cytoskeletal Organization in E-Cadherin-Deficient Cells.
AB  - The CDH1 gene, which encodes the cell-to-cell adhesion protein E-cadherin, is
      frequently mutated in lobular breast cancer (LBC) and diffuse gastric cancer
      (DGC). However, because E-cadherin is a tumor suppressor protein and lost from
      the cancer cell, it is not a conventional drug target. To overcome this, we have
      taken a synthetic lethal approach to determine whether the loss of E-cadherin
      creates druggable vulnerabilities. We first conducted a genome-wide siRNA screen
      of isogenic MCF10A cells with and without CDH1 expression. Gene ontology analysis
      demonstrated that G-protein-coupled receptor (GPCR) signaling proteins were
      highly enriched among the synthetic lethal candidates. Diverse families of
      cytoskeletal proteins were also frequently represented. These broad classes of E
      cadherin synthetic lethal hits were validated using both lentiviral-mediated
      shRNA knockdown and specific antagonists, including the JAK inhibitor LY2784544,
      Pertussis toxin, and the aurora kinase inhibitors alisertib and danusertib. Next,
      we conducted a 4,057 known drug screen and time course studies on the CDH1
      isogenic MCF10A cell lines and identified additional drug classes with linkages
      to GPCR signaling and cytoskeletal function that showed evidence of E-cadherin
      synthetic lethality. These included multiple histone deacetylase inhibitors,
      including vorinostat and entinostat, PI3K inhibitors, and the tyrosine kinase
      inhibitors crizotinib and saracatinib. Together, these results demonstrate that E
      cadherin loss creates druggable vulnerabilities that have the potential to
      improve the management of both sporadic and familial LBC and DGC.

PMID- 25777965
TI  - Extensive cytoreductive surgery in a Jehovah's Witness patient. A case report.
AB  - Jehovah's Witnesses are a well-known patient demographic in medicine because of
      their religious-based refusal of blood transfusion. This case report outlines the
      treatment of a Jehovah's Witness patient in need of an extensive cytoreductive
      surgery due to a peritoneal carcinomatosis of ovarian origin. The surgeons
      carried out all the recommended surgical and anaesthetic measures concluding that
      extensive cytoreductive surgery on a Jehovah's Witness is possible and that a
      complete cytoreduction can be safely performed.

PMID- 25777966
TI  - Topoisomerase-1 and -2A gene copy numbers are elevated in mismatch repair
      proficient colorectal cancers.
AB  - INTRODUCTION: Topoisomerase 1 (TOP1) and 2A (TOP2A) are potential predictive
      biomarkers for irinotecan and anthracycline treatment, respectively, in
      colorectal cancer (CRC), and we have recently reported a high frequency of gene
      gain of the TOP1 and TOP2A genes in CRC. Furthermore, Mismatch Repair (MMR)
      subtypes of CRC have been associated with benefit from adjuvant chemotherapy of
      primary CRC. Given the involvement of the topoisomerase enzymes in DNA
      replication and repair, we raised the hypothesis that an association may exist
      between TOP gene copy numbers and MMR proficiency/deficiency in CRC. MATERIAL AND
      METHODS: Test cohort: FISH analysis with an in-house TOP1/CEN20 probe mix and a
      commercially available TOP2A/CEN17 (Dako, Glostrup, Denmark) probe mix was
      performed on archival formalin fixed paraffin embedded (FFPE) tissue samples from
      18 patients with proficient MMR (pMMR) CRC and 18 patients with deficient MMR
      (dMMR) CRC. TOP1 and TOP2A gene copy numbers and their ratios per nucleus were
      correlated with MMR status using the Mann-Whitney test. Validation cohort: FFPE
      samples from 154 patients with primary stage III CRC (originally included in the
      RANX05 study) were classified according to MMR status by immunohistochemical
      analysis using validated antibodies for MLH1, MLH2, MSH6 and PMS2, and
      information on TOP1, CEN20, TOP2A and CEN17 status was previously published for
      this cohort. RESULTS: The observed TOP1 gene copy numbers in the 36 CRC test
      cohort were significantly greater (p < 0.01) in the pMMR subgroup (mean: 3.84,
      SD: 2.03) than in the dMMR subgroup (mean: 1.50, SD: 0.12). Similarly, the TOP2A
      copy numbers were significantly greater (p < 0.01) in the pMMR subgroup (mean:
      1.99, SD: 0.52) than in the dMMR subgroup (mean: 1.52, SD: 0.10). These findings
      were confirmed in the validation cohort, where in the pMMR subgroup 51% had >=2
      extra TOP1 copies per cell, while all tumors classified as dMMR had diploid TOP1
      status and mean TOP2A copy numbers were 2.30 (SD: 1.36) and 1.80 (SD: 0.31) (p =
      0.01) in the pMMR subgroup vs. dMMR subgroup, respectively. DISCUSSION AND
      CONCLUSION: Our results show that TOP1 and TOP2A gene copy numbers are increased
      in the pMMR subgroup. We propose that this preference may reflect a selective
      pressure to gain and/or maintain the gained extra copies of topoisomerase genes
      whose products are required to cope with high replication stress present in the
      pMMR tumors, thereby providing a survival advantage selectively in pMMR tumors.
      Future studies should test this concept and explore potential differences between
      pMMR and dMMR tumors in response to Top1 and Top2 inhibitors.

PMID- 25777968
TI  - The effect of Syphacia muris on nutrient digestibility in laboratory rats.
AB  - This study was carried out to investigate how pinworm infection in rats affects
      nutrient digestibility in the hosts. Twenty-four male outbred Wistar rats were
      randomly divided into two groups of 12 rats each. The rats from the first group
      (GI) were kept in cages with bedding containing pinworm eggs, and the second
      (control) group (GII) were kept in a separate room in clean, uncontaminated
      filter-top cages. The animals were put into individual metabolic cages later.
      Metabolic trials lasted five days and records of animal weight, food ingestion,
      and faecal weight were taken daily. Based on laboratory analysis of the feed and
      faecal nutrient content, digestibility values were determined. On day 15 of the
      experiment, the animals were euthanized. Although Syphacia muris were found in
      all rats from the GI group, animals exhibited no clinical signs. In our
      experiment, S. muris infection reduced the overall digestibility of all measured
      nutrients (P < 0.01). The most significant differences in digestibility were
      observed in the case of crude fibre and mineral matter (P < 0.01).

PMID- 25777967
TI  - Hitting the right spot: Mechanism of action of OPB-31121, a novel and potent
      inhibitor of the Signal Transducer and Activator of Transcription 3 (STAT3).
AB  - STAT3 is a key element in many oncogenic pathways and, like other transcription
      factors, is an attractive target for development of novel anticancer drugs.
      However, interfering with STAT3 functions has been a difficult task and very few
      small molecule inhibitors have made their way to the clinic. OPB-31121, an
      anticancer compound currently in clinical trials, has been reported to affect
      STAT3 signaling, although its mechanism of action has not been unequivocally
      demonstrated. In this study, we used a combined computational and experimental
      approach to investigate the molecular target and the mode of interaction of OPB
      31121 with STAT3. In parallel, similar studies were performed with known STAT3
      inhibitors (STAT3i) to validate our approach. Computational docking and molecular
      dynamics simulation (MDS) showed that OPB-31121 interacted with high affinity
      with the SH2 domain of STAT3. Interestingly, there was no overlap of the OPB
      31121 binding site with those of the other STAT3i. Computational predictions were
      confirmed by in vitro binding assays and competition experiments along with site
      directed mutagenesis of critical residues in the STAT3 SH2 domain. Isothermal
      titration calorimetry experiments demonstrated the remarkably high affinity of
      OPB-31121 for STAT3 with Kd (10 nM) 2-3 orders lower than other STAT3i. Notably,
      a similar ranking of the potency of the compounds was observed in terms of
      inhibition of STAT3 phosphorylation, cancer cell proliferation and clonogenicity.
      These results suggest that the high affinity and efficacy of OPB-31121 might be
      related to the unique features and mode of interaction of OPB-31121 with STAT3.
      These unique characteristics make OPB-31121 a promising candidate for further
      development and an interesting lead for designing new, more effective STAT3i. 

PMID- 25777969
TI  - Albiglutide: a review of its use in patients with type 2 diabetes mellitus.
AB  - Albiglutide (Eperzan((r)), Tanzeum((r))), administered subcutaneously once
      weekly, is a glucagon-like peptide (GLP)-1 receptor agonist approved for the
      treatment of type 2 diabetes mellitus in several countries. Albiglutide has a
      longer half-life than native GLP-1, since it is resistant to degradation by the
      dipeptidyl peptidase-4 enzyme. As an incretin mimetic, albiglutide enhances
      glucose-dependent insulin secretion, suppresses inappropriate glucagon secretion,
      delays gastric emptying and reduces food intake. Several phase III clinical
      trials have demonstrated the efficacy of albiglutide in terms of improving
      glycaemic control in patients with inadequately controlled type 2 diabetes,
      including its use as monotherapy or add-on therapy to other antidiabetic agents
      (e.g. metformin, sulfonylureas, thiazolidinediones and insulins). In addition to
      improving glycaemic control, albiglutide had beneficial effects on bodyweight.
      These improvements in glycaemic control and reductions in bodyweight were
      maintained during long-term treatment (up to 3 years). Albiglutide was generally
      well tolerated in clinical trials, with mild to moderate gastrointestinal adverse
      events seen most commonly. Albiglutide has a convenient once-weekly
      administration regimen and a low risk of hypoglycaemia (except when used in
      combination with agents that may be associated with hypoglycaemia, such as
      sulfonylureas or insulin). Thus, albiglutide is an effective and generally well
      tolerated treatment option for patients with inadequately controlled type 2
      diabetes. 

PMID- 25777971
TI  - Cu-catalyzed oxidative Povarov reactions between N-alkyl N-methylanilines and
      saturated oxa- and thiacycles.
AB  - Cu-catalyzed oxidative Povarov reactions between N,N-dialkylanilines and
      saturated oxa- or thiacycles with tert-butyl hydroperoxide (TBHP) are described;
      notably, the reactions use neither [4pi] nor [2pi]-motifs as the initial
      reagents. The use of cheap alkane-based substances as building units is of
      mechanistic and practical interest as two inert sp(3) C-H bonds are activated. 

PMID- 25777970
TI  - Clinical use of conditioned media of adipose tissue-derived stem cells in female
      pattern hair loss: a retrospective case series study.
AB  - BACKGROUND: Female pattern hair loss (FPHL) is a common disorder but presents
      severe psychosocial problems in many female patients. Adipose tissue-derived stem
      cells (ADSCs) and conditioned media of ADSCs (ADSC-CM) are reported to promote
      hair growth in vitro. However, there are no clinical reports on the treatment of
      alopecia using ADSC-CM. OBJECTIVES: This study evaluates our clinical experience
      in the use of ADSC-CM for the treatment of FPHL. METHODS: A retrospective,
      observational study of outcomes in 27 patients with FPHL treated with ADSC-CM was
      performed. To evaluate the efficacy of the treatment, patients' medical records
      and phototrichographic images were analyzed. RESULTS: The application of ADSC-CM
      showed efficacy in treating FPHL after 12 weeks of therapy. Hair density
      increased from 105.4 to 122.7 hairs/cm(2) (P < 0.001). Hair thickness increased
      from 57.5 MUm to 64.0 MUm (P < 0.001). None of the patients reported severe
      adverse reactions. CONCLUSIONS: The application of ADSC-CM is a potential
      treatment option for FPHL.

PMID- 25777972
TI  - Coffee and Caffeine Are Associated With Decreased Risk of Advanced Hepatic
      Fibrosis Among Patients With Hepatitis C.
AB  - BACKGROUND & AIMS: Coffee or caffeine has been proposed to protect against
      hepatic fibrosis, but few data are available on their effects in patients with
      chronic hepatitis C virus (HCV) infection. METHODS: We conducted a cross
      sectional study of veterans with chronic HCV infection to evaluate the
      association between daily intake of caffeinated and decaffeinated coffee, tea,
      and soda, and level of hepatic fibrosis, based on the FibroSURE test
      (BioPredictive, Paris, France) (F0-F3, mild [controls] vs. F3/F4-F4, advanced).
      Models were adjusted for multiple potential confounders including age, alcohol
      abuse, and obesity. RESULTS: Among 910 patients with chronic HCV infection, 98%
      were male and 38% had advanced hepatic fibrosis. Daily intake of caffeinated
      coffee was higher among controls than patients with advanced fibrosis (1.37 vs.
      1.05 cups/d; P = .038). In contrast, daily intake of caffeinated tea (0.61 vs.
      0.56 cups/d; P = .651) or soda (1.14 vs. 0.95 cans/d; P = .106) did not differ
      between the groups. A higher percentage of controls (66.0%) than patients with
      advanced fibrosis (57.9%) consumed 100 mg or more of caffeine daily from all
      sources (P = .014); controls also received a larger proportion of their caffeine
      from coffee (50.2% vs. 43.0%; P = .035). Hepatoprotective effects of an average
      daily intake of 100 mg or more of caffeine (adjusted odds ratio, 0.71; 95%
      confidence interval, 0.53-0.95; P = .020) and 1 cup or more of caffeinated tea by
      non-coffee drinkers (adjusted odds ratio, 0.56; 95% confidence interval, 0.34
      0.94; P = .028) persisted after adjustment for confounders, including insulin
      resistance. CONCLUSIONS: A modest daily caffeine intake (as little as 100 mg) may
      protect against advanced hepatic fibrosis in men with chronic HCV infection.
      Additional research is needed to confirm these findings in women and in people
      with other chronic liver diseases.

PMID- 25777973
TI  - Ser341Pro MYOC gene mutation in a family with primary open-angle glaucoma.
AB  - Glaucoma is known to induce visual impairment and blindness. The aim of the
      present study was to determine the clinical and genetic findings of a family with
      primary open-angle glaucoma (POAG). A family diagnosed with glaucoma was examined
      clinically and followed up for five years. Genomic DNA was extracted from the
      venous blood of 12 family members, and of 100 healthy individuals. The mode of
      inheritance was determined by the pedigree analysis. The third exon and its
      flanking introns of myocilin (MYOC) were amplified, and quantitative polymerase
      chain reaction (qPCR) products were sequenced. The restriction fragment length
      polymorphism analysis was performed on samples from the 12 family members and 100
      normal controls. The predicted effects of the detected variants on the secondary
      structure of the MYOC protein were analyzed by the Garnier-Osguthorpe-Robson
      method. In this family, three members were diagnosed with POAG, and one member
      with ocular hypertension. The mode of inheritance of the family was autosomal
      dominant with six members being genetically affected. The heterozygous mutation
      was identified in the third exon of MYOC that revealed a T -> C transition at
      position 1021 (p.S341P), which switched serine (Ser) to proline (Pro). This is a
      missense mutation eliminating a CviKI-1 restriction site that segregated the
      affected members. Secondary structure prediction of p.S341P suggested that the
      MYOC protein was misfolded. Ser341Pro MYOC mutation was detected in the family
      with POAG. The clinical and genetic characteristics of this mutation require
      further investigation. The mutation spectrum of MYOC may be expanded for a better
      diagnosis and treatment for POAG patients.

PMID- 25777974
TI  - The prognostic factors for locally advanced cervical cancer patients treated by
      intensity-modulated radiation therapy with concurrent chemotherapy.
AB  - BACKGROUND/PURPOSE: To identify the prognostic factors for locally advanced
      cervical cancer patients treated by intensity-modulated radiotherapy (IMRT) and
      concurrent cisplatin-based chemotherapy. METHODS: A total of 125 patients with
      stage IB2-III cervical carcinoma were treated with IMRT and concurrent cisplatin
      based chemotherapy, plus high dose rate (HDR) brachytherapy between January 2004
      and November 2010, in our institution. All patients received external irradiation
      of 45-54 Gy with the IMRT technique and concurrent cisplatin-based chemotherapy
      monthly or weekly. HDR brachytherapy of 20-30.5 Gy was prescribed to point A, as
      a local boost. Prognostic factors including age, histology, stage, lymph nodes
      metastasis, pretreatment hemoglobin level, serum squamous cell carcinoma antigen
      (serum SCC-Ag), chemotherapy regimens and the cumulative dose of weekly
      cisplatin, were analyzed. The endpoints were overall survival (OS), local failure
      free survival (LFFS) and disease-free survival (DFS). RESULTS: The median follow
      up time was 42 months. The 4-year OS, LFFS and DFS were 73.8%, 77.9% and 67.2%,
      respectively. Four (3.2%) patients developed >=grade 3 acute gastrointestinal
      (GI) toxicity and 29 (23.2%) patients developed >=grade 3 acute hematological
      toxicity. Five (4.0%) patients developed >=grade 3 late GI toxicity and seven
      (5.6%) patients developed >=grade 3 late genitourinary system toxicity. On
      univariate analysis, adenocarcinoma was a poor prognostic factor for OS (p =
      0.05), LFFS (p = 0.01) and DFS (p = 0.006). Patients with lymph nodes metastasis
      at diagnosis had worse OS (p = 0.02). The high cumulative dose of cisplatin (>180
      mg/m(2)) had better OS (p = 0.03) and tended to have better survival on LFFS (p =
      0.13) and DFS (p = 0.10). On multivariate analysis, adenocarcinoma was a
      significant independent prognostic factor for OS (p = 0.001), LFFS (p = 0.005)
      and DFS (p < 0.001). Initial lymph nodes metastasis was an independent predictor
      of OS (p = 0.013). Cumulative dose of weekly cisplatin significantly affected OS
      (p = 0.041), and high cumulative dose of cisplatin tended to have better LFFS (p
      = 0.083). Higher pretreatment hemoglobin level had better LFFS (p = 0.034).
      CONCLUSION: Adenocarcinoma and lymph nodes metastases were poor prognostic
      factors for patients with locally advanced cervical cancer. Lower pretreatment
      hemoglobin level had poorer local control. Chemotherapy with a high cumulative
      dose of cisplatin tended to result in better survival.

PMID- 25777975
TI  - Treatment effects of combining social skill training and parent training in
      Taiwanese children with attention deficit hyperactivity disorder.
AB  - BACKGROUND/PURPOSE: Children with attention-deficit/hyperactivity disorder (ADHD)
      often have problems in social interactions. We investigated the social and
      behavioral effects of providing both social skill training and parent training to
      school-aged children with ADHD in Taiwan. METHODS: Seven consecutive 8-week
      behavioral-based social skill training (SST) group sessions were held for 48
      children with ADHD; parallel 8-week parent group sessions were provided
      simultaneously. Fifty-five children with ADHD were recruited as a control group.
      All children took medication as prescribed by their doctors. The effects were
      assessed using the teacher and parent version of the Chinese version of Swanson,
      Nolan, and Pelham, version IV scale (SNAP-IV), the Chinese version of the Child
      Behavior Check List (CBCL-C), child and teacher version of the modified Social
      Skill Rating System (SSRS-C and SSRS-T), at baseline, post-treatment, and 4
      months from baseline. The doses of methylphenidate and drug compliance were
      controlled during the analysis. RESULTS: The mixed-effects model demonstrated the
      main effect of group sessions on the Oppositional subscale of SNAP-P, the
      Anxious/Depressed subscale of CBCL-C, the Self Control subscale of SSRS-C, and
      the Active Participation subscale of SSRS-T, all in favor of the experimental
      group. However, the improvement on the Oppositional subscale of SNAP-P and the
      Self Control subscale of SSRS-C were noted only between baseline and post
      treatment period and were not sustained at the end of the follow-up period.
      CONCLUSION: Our study demonstrated that children with ADHD could benefit from
      this low intensity psychosocial program, although some improvements were not
      maintained at follow-up assessment.

PMID- 25777976
TI  - Body mass index and age are predictors for symptom improvement after high-power
      laser vaporization for benign prostatic hyperplasia.
AB  - BACKGROUND/PURPOSE: To evaluate the effectiveness and safety of high-power 120W
      Greenlight HPS laser (HPS) and compare the results to transurethral resection of
      the prostate (TURP), and define a subgroup of patients who had better symptom
      score improvement after HPS. METHODS: One hundred and twenty-five patients who
      underwent surgery for benign prostatic hyperplasia (BPH) (61 HPS and 64 TURP)
      were retrospectively followed. Improvements of International Prostate Symptom
      Score (IPSS), quality of life score (QoL), maximum flow rate (Qmax) and post-void
      residual (PVR) were assessed at 4 weeks after the procedures. Potential
      covariates including age, body mass index (BMI), prostate volume (PV) and serum
      prostate-specific antigen (PSA) were defined and further subgroup analyses were
      utilized. RESULTS: The HPS group had a significantly higher education level,
      annual household income and larger prostate size. Compared with TURP, HPS
      resulted in comparable IPSS, QoL, Qmax and PVR improvements, but shorter
      hospitalization duration, serum hemoglobin loss and blood transfusion rate.
      Subgroup analyses showed that men in the HPS group were younger (age<76 years),
      had higher BMI (>=24kg/m(2)) and greater adjusted IPSS and QoL improvements than
      men in the TURP group. CONCLUSION: HPS offered adequate effectiveness for
      symptomatic BPH versus TURP and was advantageous with regard to operative safety.
      Patients who are younger and have higher BMI may achieve better improvements with
      HPS than with TURP. Further long-term follow-up study is warranted.

PMID- 25777977
TI  - Recurrent spontaneous massive hemothorax from intrathoracic extramedullary
      hematopoiesis resulting in respiratory failure.
AB  - Extramedullary hematopoiesis (EMH) is a compensatory response to many chronic
      anemic disorders. Intrathoracic EMH, usually presenting as paravertebral masses
      over the posterior mediastinum, is a rare entity and is usually asymptomatic.
      Hemothorax is a rare but possibly fatal complication. Local radiation for
      intrathoracic EMH is considered effective in preventing its recurrence. Here we
      describe a patient who had had alpha-thalassemia for many years and developed a
      spontaneous left-sided hemothorax from EMH. A chest film and a chest computed
      tomography (CT) scan had showed multiple paravertebral masses over the lower
      thoracic spine with left-sided pleural effusion. A pathological diagnosis of EMH
      was made by video-assisted thoracoscopic surgery. The patient had not received
      preventive local chest radiation. Ten years later, he suffered from a life
      threatening hemothorax complicated by acute respiratory failure without traumatic
      history. A CT scan showed posterior mediastinal masses over the lower thoracic
      spine with right-sided pleural effusion. Thoracoscopy was performed to remove the
      blood clot in the pleural space for successful weaning from mechanical
      ventilation. This is the first case of intrathoracic EMH to have recurrent
      hemothorax associated with acute respiratory failure. 

PMID- 25777978
TI  - Bronchiolitis obliterans complicating a pneumothorax after Stevens-Johnson
      syndrome induced by lamotrigine.
AB  - Bronchiolitis obliterans (BO) was defined as a nonreversible obstructive lung
      disease in which the bronchioles are always compressed and narrowed by fibrosis
      or inflammation. In the severe event of lung collapse after BO, surgical
      intervention is often recommended, and conservative therapy is thought to be
      ineffective. Here, we report the case of a 9-year old girl clinically diagnosed
      as having bronchiolitis obliterans with abrupt occlusion of the right B4b
      bronchus. After a lamotrigine-induced Stevens-Johnson syndrome (SJS) occurred,
      she presented with total collapse of the right lung on admission, which was
      subsequently complicated by a pneumothorax during conservative treatment, but
      with the re-expansion of the right upper lobe after intervention. The case
      indicates the possibility of reversing pulmonary atelectasis in BO. Thus, surgery
      may not be necessary. 

PMID- 25777979
TI  - Enzyme immunoassay and proteomic characterization of troponin I as a marker of
      mammalian muscle compounds in raw meat and some meat products.
AB  - The skeletal muscle protein troponin I (TnI) has been characterized as a
      potential thermally stable and species-specific biomarker of mammalian muscle
      tissues in raw meat and meat products. This study proposed a technique for the
      quantification of TnI comprising protein extraction and sandwich enzyme-linked
      immunosorbent assay (ELISA). The technique is characterized by a TnI detection
      limit of 4.8 ng/ml with quantifiable concentrations ranging from 8.7 to 52 ng/ml.
      The method was shown to be suitable for detection of TnI in mammalian (beef,
      pork, lamb, and horse) meat but not in poultry (chicken, turkey, and duck) meat.
      In particular, the TnI content in beef was 0.40 3 +/- 0.058 mg/g of wet tissue.
      The TnI estimations obtained for the pork and beef samples using ELISA were
      comparable to the proteomic analysis results. Thus, the quantitative study of TnI
      can be a convenient way to assess the mammalian muscle tissue content of various
      meat products.

PMID- 25777980
TI  - Cue competition effects in human causal learning.
AB  - Five experiments involving human causal learning were conducted to compare the
      cue competition effects known as blocking and unovershadowing, in proactive and
      retroactive instantiations. Experiment 1 demonstrated reliable proactive blocking
      and unovershadowing but only retroactive unovershadowing. Experiment 2 replicated
      the same pattern and showed that the retroactive unovershadowing that was
      observed was interfered with by a secondary memory task that had no demonstrable
      effect on either proactive unovershadowing or blocking. Experiments 3a, 3b, and
      3c demonstrated that retroactive unovershadowing was accompanied by an inflated
      memory effect not accompanying proactive unovershadowing. The differential
      pattern of proactive versus retroactive cue competition effects is discussed in
      relationship to amenable associative and inferential processing possibilities. 

PMID- 25777981
TI  - PLU-1/JARID1B overexpression predicts proliferation properties in head and neck
      squamous cell carcinoma.
AB  - PLU-1/JARID1B (jumonji AT rich interactive domain 1B) is one of the testis cancer
      antigens and functions as a histone demethylase in the regulation of various
      human types of cancers. However, its functions in head and neck squamous cell
      carcinoma (HNSCC) are rarely reported. The aim of the present study was to
      examine PLU-1/JARID1B expression levels in HNSCCs and to investigate its role in
      cancer cell proliferation. In the present study, we found that PLU-1/JARID1B mRNA
      was upregulated in all tested HNSCC cell lines. Immunohistochemical staining
      showed that PLU-1/JARID1B protein expression was detected in 87.8% (87/99) of the
      HNSCC cases. A positive association was observed between high PLU-1/JARID1B
      expression and higher Ki-67 labeling in the HNSCC samples (Pearson r=0.6514,
      P=0.0003). Stable PLU-1/JARID1B knockdown by PLU-1-shRNAs in the HNSCC cell lines
      suppressed cell growth both in the in vitro and in vivo studies. Moreover, PLU
      1/JARID1B knockdown resulted in G1 arrest and early apoptosis by suppressing Bcl
      2 family members in the HNSCCs. These data indicate that PLU-1/JARID1B is
      overexpressed in HNSCCs and is associated with tumor proliferation and apoptosis.
      Therefore, PLU-1/JARID1B represents a candidate proliferation biomarker for HNSCC
      diagnosis and treatment.

PMID- 25777982
TI  - Multifunctional lanthanide and silver ion co-doped nano-chlorapatites with
      combined spectroscopic and antimicrobial properties.
AB  - Nanocrystalline chlorapatites (Ca10(PO4)6Cl2) doped with lanthanide ions (Eu(3+),
      Er(3+) and Yb(3+)) and co-doped with silver ions (Ag(+)) were synthesized by a
      hydrothermal synthesis route. XRD, TEM, and SAED measurements indicated that the
      powders are single phased and crystallize with a hexagonal structure with good
      dispersion. The results showed well crystallized chlorapatite grains with a
      diameter of about 45 nm. The antimicrobial activity of the nanoparticles against
      Escherichia coli ATCC 11229 and ATCC 25922, Klebsiella pneumoniae ATCC 700603,
      and Pseudomonas aeruginosa PAO1 and ATCC 27853 was studied. The best activity was
      observed for the Eu(3+),Ag(+):Ca10(PO4)6Cl2 and Eu(3+),Ag(+),Yb(3+):Ca10(PO4)6Cl2
      compositions. These multifunctional nanocrystalline powders could be used as a
      promising antimicrobial agent and material for bio-detection. 

PMID- 25777983
TI  - Time-trends in the prescribing of gastroprotective agents to primary care
      patients initiating low-dose aspirin or non-steroidal anti-inflammatory drugs: a
      population-based cohort study.
AB  - AIMS: Low-dose aspirin (LDA) and non-steroidal-anti-inflammatory drugs (NSAIDs)
      both increase the risk of upper gastrointestinal events (UGIEs). In the
      Netherlands, recommendations regarding the prescription of gastroprotective
      agents (GPAs) in LDA users were first issued in 2009 in the HARM-Wrestling
      consensus. National guidelines on gastroprotective strategies (GPSs) in NSAID
      users were issued in the first part of the preceding. The aim of the present
      study was to examine time-trends in GPSs in patients initiating LDA and those
      initiating NSAIDs between 2000 and 2012. METHODS: Within a large electronic
      primary healthcare database, two cohorts were selected: (i) patients newly
      prescribed LDA and (ii) patients newly prescribed NSAIDs between 2000 and 2012.
      Patients who had been prescribed a GPA in the previous six months were excluded.
      For both cohorts, patients' risk of a UGIE was classified as low, moderate or
      high, based on the HARM-Wrestling consensus, and the presence of an adequate
      GPSwas determined. RESULTS: A total of 37 578 patients were included in the LDA
      cohort and 352 025 patients in the NSAID cohort. In both cohorts, an increase in
      GPSs was observed over time, but prescription of GPAs was lower in the LDA
      cohort. By 2012, an adequate GPS was present in 31.8% of high-risk LDA
      initiators, vs. 48.0% of high-risk NSAID initiators. CONCLUSIONS: Despite a
      comparable risk of UGIEs, GPSs are prescribed less in high-risk LDA initiators
      than in high-risk NSAID initiators. For both groups of patients, there is still
      room for improvement in guideline adherence.

PMID- 25777984
TI  - Roles of leptin in bone metabolism and bone diseases.
AB  - Adipose tissue has been more accepted as an active contributor to whole body
      homeostasis, rather than just a fat depot, since leptin, a 16 kDa protein, was
      discovered as the product of the obese gene in 1994. With more and more studies
      conducted on this hormone, it has been shown that there is a close relationship
      between adipose tissue and bone, which have important effects on each other. Bone
      is the source of many hormones, such as osteocalcin, that can affect energy
      metabolism and then the anabolism or catabolism of fat tissue. In contrast, the
      adipose tissue synthesizes and releases a series of adipokines, which are
      involved in bone metabolism through direct or indirect effects on bone formation
      and resorption. Interestingly, leptin, one of the most important cytokines
      derived from fat tissue, seems to account for the largest part of effects on
      bone, through direct or indirect involvement in bone remodeling and by playing a
      significant role in many bone diseases, such as osteoporosis, osteoarthritis,
      rheumatic arthritis, bone tumors and even fractures. In this review, we will
      discuss the progress in leptin research, particularly focusing on the roles of
      leptin in bone diseases. 

PMID- 25777985
TI  - Enantiospecific photoresponse of sterically hindered diarylethenes for
      chiroptical switches and photomemories.
AB  - Light-driven transcription, replication and enzyme catalysis are critically
      dependent upon a delicate transfer between molecular and supramolecular
      chirality. Chemists have well realized the impressive stereospecificity over many
      thermally accessible cycloaddition with chiral catalysts, but making light work
      in the enantiomer control of diarylethene photocyclization has proved to be more
      challenging. Here, we report a unique sterically hindered diarylethene (BBTE)
      system with absolute enantiospecific photocyclization and cycloreversion.
      Moreover, we have fully separated all the five thermally stable isomers,
      consisting of one achiral parallel conformer, one pair of anti-parallel ring-open
      enantiomers, and another pair of ring-closed enantiomers, whose absolute chiral
      configurations are entirely elucidated by single X-ray crystallographic analyses.
      The photo-responsive feature exhibits a reversible, complete enantio-control
      transformation without racemism, offering an unrivaled unimolecular
      enantiospecific platform for potential applications as bistable chiroptical
      switches and all-photonic photomemories with optical rotation as non-destructive
      readout. 

PMID- 25777986
TI  - The role of the microbiota in ageing: current state and perspectives.
AB  - Since the application of high-throughput technologies to investigate complex
      microbial communities, alterations in the human gut microbiota have been
      associated with an increasing number of diseases and conditions. This field of
      research has developed into an area of intense study which is quite different to
      the microbial investigations that have preceded it in terms of both the broadness
      of the area of research and the complexity of the analyses. In this review, we
      discuss gut microbiota changes observed in ageing in the context of the
      physiological changes that accompany senescence, examine what correlations can be
      established or inferred, and we discuss what key questions remain to be answered
      in the field. WIREs Syst Biol Med 2015, 7:131-138. doi: 10.1002/wsbm.1293 For
      further resources related to this article, please visit the WIREs website.
      CONFLICT OF INTEREST: PWOT is funded by a nonrestrictive research award from
      General Mills Inc.

PMID- 25777987
TI  - Effect of web-based training for Department of Motor Vehicle staff on donor
      designation rates: results of a statewide randomized trial.
AB  - On approach to addressing the continual shortage of organ donors is to encourage
      people to join a state donor registry. Joining the registry saves time and
      assures family members that organ donation is what their loved one would want.
      However, fewer than half of adults have taken this step. We tested a brief, web
      based training program for department of motor vehicles (DMV) staff that educates
      them about organ and tissue donation and also models the correct way to interact
      with customers. The intervention was developed with extensive input and active
      participation from DMV staff. After a small-scale pilot test, all DMV offices
      across the state of West Virginia (WV) were randomized to receive the training or
      serve as a comparison group. The results showed that customers of DMV staff who
      had received the training were 7.5% more likely to register as organ donors. A
      conservative estimate is that this generates approximately 800 additional donor
      designations per month. An important aspect of web-based training is that once it
      has been deployed, it can continue to be used without incurring additional cost;
      the state of WV currently requires all new employees to complete the training
      program. This type of training can be adopted nationwide. 

PMID- 25777992
TI  - Redistribution of Emergency Department Patients After Disaster-Related Closures
      of a Public Versus Private Hospital in New York City.
AB  - Sudden hospital closures displace patients from usual sources of care and force
      them to access facilities that lack their prior medical records. For patients
      with complex needs and for nearby hospitals already strained by high volume,
      disaster-related hospital closures induce a public health emergency. Our
      objective was to analyze responses of patients from public versus private
      emergency departments after closure of their usual hospital after Hurricane
      Sandy. Using a statewide database of emergency visits, we followed patients with
      an established pattern of accessing 1 of 2 hospitals that closed after Hurricane
      Sandy: Bellevue Hospital Center and NYU Langone Medical Center. We determined how
      these patients redistributed for emergency care after the storm. We found that
      proximity strongly predicted patient redistribution to nearby open hospitals.
      However, for patients from the closed public hospital, this redistribution was
      also influenced by hospital ownership, because patients redistributed to other
      public hospitals at rates higher than expected by proximity alone. This
      differential response to hospital closures demonstrates significant differences
      in how public and private patients respond to changes in health care access
      during disasters. Public health response must consider these differences to meet
      the needs of all patients affected by disasters and other public health
      emergencies.

PMID- 25777988
TI  - Progranulin knockout accelerates intervertebral disc degeneration in aging mice.
AB  - Intervertebral disc (IVD) degeneration is a common degenerative disease, yet much
      is unknown about the mechanisms during its pathogenesis. Herein we investigated
      whether progranulin (PGRN), a chondroprotective growth factor, is associated with
      IVD degeneration. PGRN was detectable in both human and murine IVD. The levels of
      PGRN were upregulated in murine IVD tissue during aging process. Loss of PGRN
      resulted in an early onset of degenerative changes in the IVD tissue and altered
      expressions of the degeneration-associated molecules in the mouse IVD tissue.
      Moreover, PGRN knockout mice exhibited accelerated IVD matrix degeneration,
      abnormal bone formation and exaggerated bone resorption in vertebra with aging.
      The acceleration of IVD degeneration observed in PGRN null mice was probably due
      to the enhanced activation of NF-kappaB signaling and beta-catenin signaling.
      Taken together, PGRN may play a critical role in homeostasis of IVD, and may
      serve as a potential molecular target for prevention and treatment of disc
      degenerative diseases. 

PMID- 25777993
TI  - Brief Report: IFIH1 Mutation Causes Systemic Lupus Erythematosus With Selective
      IgA Deficiency.
AB  - OBJECTIVE: To identify the underlying genetic defect in a 16-year-old girl with
      severe early-onset and refractory systemic lupus erythematosus (SLE), IgA
      deficiency, and mild lower limb spasticity without neuroradiologic
      manifestations. METHODS: Whole-exome sequencing and extensive immunologic
      analysis were performed on samples from the index patient. RESULTS: We identified
      a de novo p.R779H IFIH1 gain-of-function mutation in a patient with severe early
      onset SLE, selective IgA deficiency, and mild lower limb spasticity. The same
      mutation in IFIH1 was recently identified in patients with Aicardi-Goutieres
      syndrome, a rare neuroimmunologic disorder associated with elevated levels of
      type I interferon (IFN). IFN induced with helicase C domain 1 functions as an
      intracellular innate immune receptor that senses viral nucleic acids and leads to
      the induction of type I IFN and proinflammatory cytokines. Despite systemic
      immunosuppressive treatment, disease activity persisted in the patient and was
      associated with elevated serum levels of IFNalpha and up-regulation of IFIH1
      itself. CONCLUSION: This finding adds a new genetic causation for Mendelian lupus
      and greatly extends the disease spectrum associated with mutations in IFIH1
      (ranging from inflammatory encephalopathy to prototypic systemic autoimmune
      disease). This marked phenotypic heterogeneity, despite an identical mutation,
      demonstrates the importance of modifying factors in type I IFN-dependent
      pathologies caused by mutations in IFIH1.

PMID- 25777994
TI  - Appearance of hepatobiliary diseases in a population-based cohort with
      inflammatory bowel diseases (Inflammatory Bowel Disease Cohort of the Uppsala
      Region).
AB  - BACKGROUND AND AIM: To prospectively follow the evolution of hepatobiliary
      diseases in a population-based cohort of patients with inflammatory bowel
      diseases. METHODS: Between 2005 and 2009, 790 incident cases of ulcerative
      colitis and Crohn's disease were registered in the Uppsala Health Region,
      corresponding to an average incidence of 20.0 and 9.9 new cases/100 000
      inhabitants/year, respectively. Liver function tests were analyzed in 97.1% and
      the results of ensuing investigations were summarized. RESULTS: Seventeen
      patients with primary sclerosing cholangitis were diagnosed corresponding to an
      overall prevalence of 2.2% (ulcerative colitis 1.7% and Crohn's disease 3.0%,
      respectively). The median age at diagnosis was 25 years (interquartile range:
      17.0-34.0). Among the 92 patients below 17 years of age, three had autoimmune
      hepatitis and three primary sclerosing cholangitis, summing up to a prevalence of
      6.5% immune-mediated hepatobiliary diseases among the pediatric patients. Three
      patients have undergone liver transplantation and one died of colonic carcinoma.
      Ten patients have demonstrated persistent elevation of alkaline phosphatases but
      had a normal magnetic resonance cholangiopancreatography (two patients) or
      refused further investigation (one patient). CONCLUSION: In this first large
      prospective population-based cohort of 526 patients with ulcerative colitis (UC)
      and 264 with Crohn's disease, 17 cases of primary sclerosing cholangitis were
      found, among whom three (17%) so far have been liver transplanted and one has
      died of colon carcinoma. The average age of those affected by primary sclerosing
      cholangitis is considerably lower than usually reported. Ten patients had or have
      had elevated alkaline phosphatase without confirmed liver or biliary disease.

PMID- 25777995
TI  - Systemic delivery of proresolving lipid mediators resolvin D2 and maresin 1
      attenuates intimal hyperplasia in mice.
AB  - Vascular injury induces a potent inflammatory response that influences vessel
      remodeling and patency, limiting long-term benefits of cardiovascular
      interventions such as angioplasty. Specialized proresolving lipid mediators
      (SPMs) derived from omega-3 polyunsaturated fatty acids [eicosapentaenoic acid
      and docosahexaenoic acid (DHA)] orchestrate resolution in diverse settings of
      acute inflammation. We hypothesized that systemic administration of DHA-derived
      SPMs [resolvin D2 (RvD2) and maresin 1 (MaR1)] would influence vessel remodeling
      in a mouse model of arterial neointima formation (carotid ligation). In vitro,
      SPM treatment inhibited mouse aortic smooth muscle cell migration (IC50 ? 1 nM)
      to a PDGF gradient and reduced TNF-alpha-stimulated p65 translocation, superoxide
      production, and proinflammatory gene expression (MCP-1). In vivo, adult FVB mice
      underwent unilateral carotid artery ligation with administration of RvD2, MaR1,
      or vehicle (100 ng by intraperitoneal injection at 0, 1, 3, 5, and 7 d after
      ligation). In ligated carotid arteries at 4 d, SPM treatment was associated with
      reduced cell proliferation and neutrophil and macrophage recruitment and
      increased polarization of M2 macrophages in the arterial wall. Neointimal
      hyperplasia (at 14 d) was notably attenuated in RvD2 (62%)- and MaR1 (67%)
      treated mice, respectively. Modulation of resolution pathways may offer new
      opportunities to regulate the vascular injury response and promote vascular
      homeostasis.

PMID- 25777996
TI  - Spindle cell oncocytoma of the adenohypophysis: two case reports and a review of
      the literature.
AB  - Spindle cell oncocytoma (SCO) of the adenohypophysis is a rare tumor in the
      sellar region. Due to its rarity, little information is available regarding SCO.
      It is often misdiagnosed as another type of sellar tumor. In the present study,
      two cases of SCO were reported. One patient was a 35-year-old female presenting
      with decreased visual acuity, amenorrhea and lactation. The other patient was a
      62-year-old female with no clear symptoms or signs. Cranial magnetic resonance
      imaging (MRI) revealed a suprasellar mass with marked homogeneous enhancement in
      the two cases. A craniotomy was performed to completely resect the tumors. The
      tumors were immunopositive for vimentin, epithelial membrane antigen (EMA), S-100
      and thyroid transcription factor-1 (TTF-1). The tumors were pathologically
      diagnosed as SCO. No recurrence occurred during the follow-up period of 15-21
      months. In the present study, the literature was reviewed and the clinical data,
      imaging features, intraoperative findings and recurrence of 24 cases were
      analyzed in the literature as well as the present two cases. The average age of
      the SCO patients was 58.5 years and no gender preference was observed for the
      disease. The tumor exhibited homogeneous enhancement on the MRI. The
      intraoperative assessment revealed that the tumor had a rich blood supply and the
      SCO tumors were immunopositive for vimentin, S-100, EMA and TTF-1. These findings
      provided valuable clinical data for the preoperative diagnosis and surgical
      removal of SCO tumors.

PMID- 25777997
TI  - Full genome analysis of a European-type genotype 3 hepatitis E virus variant
      obtained from a Japanese patient with autochthonous acute hepatitis E.
AB  - A unique European-type HEV strain (HE-JA12-0725) classifiable into subgenotype 3f
      was recovered from a 66-year-old Japanese female with autochthonous acute
      hepatitis E, and its entire genomic sequence was determined and characterized.
      The HE-JA12-0725 strain shared the highest identity of 92.7% with a Spanish swine
      isolate (EU723514) over the entire genome and possessed a long hypervariable
      region sequence of 111 amino acids, identical to the 3f strains of European
      origin. The patient had consumed pork liver obtained via home delivery in Japan
      approximately two months before the disease onset. These results suggest the
      circulation of rare 3f HEV strains in Japan.

PMID- 25777998
TI  - Clinical trials in youth-onset type 2 diabetes: needs, barriers, and options.
AB  - Youth-onset type 2 diabetes (T2D) is increasingly recognized as a disorder with
      substantial risk for long-term metabolic, cardiovascular, and renal morbidity and
      mortality, as well as individual and societal burden. Recent studies suggest that
      the disorder differs from adult-onset T2D in a variety of ways and that there is
      an urgent need for an expanded set of treatment options. However, demographic,
      economic, and social challenges limit the number of eligible candidates for
      clinical trials in youth-onset T2D, and a growing number trials mandated by
      regulatory agencies have created a circumstance in which too many trials are
      chasing too few eligible participants. A solution to this situation will require
      novel approaches to clinical trial design incorporating collaboration among
      clinical investigators, pharmaceutical sponsors, and regulatory agencies. If
      successful, this approach could also serve as a model for clinical trials in
      other rare and understudied pediatric disorders. 

PMID- 25777999
TI  - The diagnosis of posttransplantation diabetes mellitus: meeting the challenges.
AB  - Posttransplantation diabetes mellitus (PTDM) is a major complication after renal
      transplantation due to its negative impact on patient and graft survival, and
      affects up to 40% of renal transplant recipients. The generation of evidence
      regarding its optimal treatment is now progressing with some emphasis on early
      postoperative insulin treatment that targets beta-cell failure. This therapy
      seems to benefit renal transplant patients but contrasts with previous PTDM
      guidelines that were following treatment of type 2 diabetes mellitus (DM): oral
      antidiabetics first, insulin last. Similarly, in the current PTDM consensus
      recommendations, diagnostic procedures are in accordance with the American
      Diabetes Association (ADA) recommendations for diagnosis of DM. PTDM and type 2
      DM, however, are distinct disease entities with different pathophysiological
      backgrounds. This review will discuss the significance of the standard diagnostic
      criteria for DM in patients after renal transplantation without prior DM. In
      particular, the role of glycated hemoglobin (HbA1c) and oral glucose tolerance
      testing (OGTT) will be reviewed. In addition, the potential role of other
      glycated proteins and continuous glucose monitoring will be covered, although
      these parameters are not yet part of the consensus recommendations.

PMID- 25778000
TI  - Food addiction in overweight and obese adolescents seeking weight-loss treatment.
AB  - Some forms of overeating closely resemble addictive behaviour. The Yale Food
      Addiction Scale (YFAS) was developed to measure such addiction-like eating in
      humans and has been employed in numerous studies for examining food addiction in
      adults. Yet, little is known about food addiction in children and adolescents.
      Fifty adolescents were recruited at the beginning of treatment in a weight-loss
      hospital and completed the YFAS among other questionnaires. Nineteen participants
      (38%) received a YFAS diagnosis, who did not differ in age, body mass and gender
      distribution from those not receiving a diagnosis. However, those with food
      addiction reported more binge days, more frequent food cravings, higher eating,
      weight and shape concerns, more symptoms of depression and higher attentional and
      motor impulsivity. Eating restraint and nonplanning impulsivity did not differ
      between groups. Results replicate findings from studies in obese adults such that
      food addiction is not related to age, gender, body mass or eating restraint, but
      to higher eating pathology, more symptoms of depression and higher impulsivity.
      Furthermore, results highlight that particularly attentional impulsivity is
      related to 'food addiction'. Addiction-like eating appears to be a valid
      phenotype in a substantial subset of treatment-seeking, obese adolescents.

PMID- 25778096
TI  - Intergenerational continuity of cell shape dynamics in Caulobacter crescentus.
AB  - We investigate the intergenerational shape dynamics of single Caulobacter
      crescentus cells using a novel combination of imaging techniques and theoretical
      modeling. We determine the dynamics of cell pole-to-pole lengths, cross-sectional
      widths, and medial curvatures from high accuracy measurements of cell contours.
      Moreover, these shape parameters are determined for over 250 cells across
      approximately 10000 total generations, which affords high statistical precision.
      Our data and model show that constriction is initiated early in the cell cycle
      and that its dynamics are controlled by the time scale of exponential
      longitudinal growth. Based on our extensive and detailed growth and contour data,
      we develop a minimal mechanical model that quantitatively accounts for the cell
      shape dynamics and suggests that the asymmetric location of the division plane
      reflects the distinct mechanical properties of the stalked and swarmer poles.
      Furthermore, we find that the asymmetry in the division plane location is
      inherited from the previous generation. We interpret these results in terms of
      the current molecular understanding of shape, growth, and division of C.
      crescentus. 

PMID- 25778097
TI  - Skin biopsy and I-123 MIBG scintigraphy findings in idiopathic Parkinson's
      disease and parkinsonism: a comparative study.
AB  - BACKGROUND: (123) I-meta-iodobenzylguanidine ((123) I-MIBG) myocardial
      scintigraphy is considered reliable in differentiating idiopathic Parkinson's
      disease (IPD) from other parkinsonisms, but it is biased by pharmacological
      treatments. Skin biopsy is not influenced by therapy and has disclosed skin
      denervation in IPD. Our aims were to compare (123) I-MIBG scintigraphy and skin
      biopsy findings in IPD and parkinsonisms to (1) verify whether myocardial and
      skin denervations are linked; (2) explore the simultaneous extent of the
      autonomic dysfunction. METHODS: We studied 22 IPD and 11 parkinsonism patients by
      means of (123) I-MIBG scintigraphy and skin biopsies. RESULTS: In the IPD group,
      both (123) I-MIBG scintigraphy and skin biopsy results were abnormal in 91% of
      patients, showing concordance in 82% of cases. In parkinsonisms, results of both
      tests were normal in all patients. CONCLUSION: (1) Skin biopsy and (123) I-MIBG
      scintigraphy provide comparable results; (2) in IPD, autonomic dysfunctions are
      often simultaneously widespread at cardiac and skin branches. (c) 2015
      International Parkinson and Movement Disorder Society.

PMID- 25778098
TI  - Refinement of IKZF1 status in pediatric Philadelphia-positive acute lymphoblastic
      leukemia.

PMID- 25778099
TI  - The Notch ligand DLL4 specifically marks human hematoendothelial progenitors and
      regulates their hematopoietic fate.
AB  - Notch signaling is essential for definitive hematopoiesis, but its role in human
      embryonic hematopoiesis is largely unknown. We show that in hESCs the expression
      of the Notch ligand DLL4 is induced during hematopoietic differentiation. We
      found that DLL4 is only expressed in a sub-population of bipotent
      hematoendothelial progenitors (HEPs) and segregates their hematopoietic versus
      endothelial potential. We demonstrate at the clonal level and through
      transcriptome analyses that DLL4(high) HEPs are enriched in endothelial
      potential, whereas DLL4(low/-) HEPs are committed to the hematopoietic lineage,
      albeit both populations still contain bipotent cells. Moreover, DLL4 stimulation
      enhances hematopoietic differentiation of HEPs and increases the amount of
      clonogenic hematopoietic progenitors. Confocal microscopy analysis of whole
      differentiating embryoid bodies revealed that DLL4(high) HEPs are located close
      to DLL4(low/-) HEPs, and at the base of clusters of CD45+ cells, resembling intra
      aortic hematopoietic clusters found in mouse embryos. We propose a model for
      human embryonic hematopoiesis in which DLL4(low/-) cells within hemogenic
      endothelium receive Notch-activating signals from DLL4(high) cells, resulting in
      an endothelial-to-hematopoietic transition and their differentiation into CD45+
      hematopoietic cells. 

PMID- 25778100
TI  - PD-L1/PD-1 presence in the tumor microenvironment and activity of PD-1 blockade
      in multiple myeloma.

PMID- 25778101
TI  - Detection of single ion channel activity with carbon nanotubes.
AB  - Many processes in life are based on ion currents and membrane voltages controlled
      by a sophisticated and diverse family of membrane proteins (ion channels), which
      are comparable in size to the most advanced nanoelectronic components currently
      under development. Here we demonstrate an electrical assay of individual ion
      channel activity by measuring the dynamic opening and closing of the ion channel
      nanopores using single-walled carbon nanotubes (SWNTs). Two canonical dynamic ion
      channels (gramicidin A (gA) and alamethicin) and one static biological nanopore
      (alpha-hemolysin (alpha-HL)) were successfully incorporated into supported lipid
      bilayers (SLBs, an artificial cell membrane), which in turn were interfaced to
      the carbon nanotubes through a variety of polymer-cushion surface
      functionalization schemes. The ion channel current directly charges the quantum
      capacitance of a single nanotube in a network of purified semiconducting
      nanotubes. This work forms the foundation for a scalable, massively parallel
      architecture of 1d nanoelectronic devices interrogating electrophysiology at the
      single ion channel level. 

PMID- 25778102
TI  - Who drinks where: youth selection of drinking contexts.
AB  - BACKGROUND: Different drinkers may experience specific risks depending on where
      they consume alcohol. This longitudinal study examined drinking patterns, and
      demographic and psychosocial characteristics associated with youth drinking in
      different contexts. METHODS: We used survey data from 665 past-year alcohol-using
      youths (ages 13 to 16 at Wave 1) in 50 midsized California cities. Measures of
      drinking behaviors and drinking in 7 contexts were obtained at 3 annual time
      points. Other characteristics included gender, age, race, parental education,
      weekly disposable income, general deviance, and past-year cigarette smoking.
      RESULTS: Results of multilevel regression analyses show that more frequent past
      year alcohol use was associated with an increased likelihood of drinking at
      parties and at someone else's home. Greater continued volumes of alcohol (i.e.,
      heavier drinking) was associated with increased likelihood of drinking at parking
      lots or street corners. Deviance was positively associated with drinking in most
      contexts, and past-year cigarette smoking was positively associated with drinking
      at beaches or parks and someone else's home. Age and deviance were positively
      associated with drinking in a greater number of contexts. The likelihood of youth
      drinking at parties and someone else's home increased over time, whereas the
      likelihood of drinking at parking lots/street corners decreased. Also, deviant
      youths progress to drinking in their own home, beaches or parks, and
      restaurants/bars/nightclubs more rapidly. CONCLUSIONS: The contexts in which
      youths consume alcohol change over time. These changes vary by individual
      characteristics. The redistribution of drinking contexts over the early life
      course may contribute to specific risks associated with different drinking
      contexts.

PMID- 25778103
TI  - Young brains on cannabis: It's time to clear the smoke.
AB  - Cannabis is the most commonly used illicit substance among youth. Recent policy
      developments and ongoing debate related to this drug underscore the urgent need
      to "clear the smoke" and better understand what the scientific evidence says
      about the health and behavioral effects of cannabis use, particularly on youth
      whose brains are undergoing rapid and extensive development. 

PMID- 25778104
TI  - Chirality extension of an oxazine building block en route to total syntheses of
      (+)-hyacinthacine A2 and sphingofungin B.
AB  - Concise and stereocontrolled syntheses of (+)-hyacinthacine A2 and sphingofungin
      B were achieved via a diastereomerically enriched oxazine intermediate. The key
      strategies include palladium(0)-catalyzed intramolecular oxazine formation and
      diastereoselective nucleophilic addition to an aldehyde. (+)-Hyacinthacine A2 was
      synthesized in 13 steps and 10.2% overall yield and the synthesis of
      sphingofungin B proceeded in a linear sequence over 15 steps and 6.9% overall
      yield from (R)-methyl 2-benzamido-3-((tert-butyldimethylsilyl)oxy)propanoate. 

PMID- 25778105
TI  - Synthesis of one-dimensional Schiff base polymers that contain an oligothiophene
      building block on the graphite surface.
AB  - Surface-mediated Schiff base coupling reactions between oligothiophenes equipped
      with an aldehyde group and aromatic diamines were investigated on highly oriented
      pyrolytic graphite (HOPG) by means of scanning tunneling microscopy (STM) under
      ambient conditions. To investigate the evolution process from monomers to
      resultant polymers and the mechanism of reactions, we controlled the ratio of
      precursors and the reactive temperature, and we obtained high-resolution STM
      images of different stages of the surface reaction. The results suggest that
      preferential adsorption of one kind of monomer has a great influence on the on
      surface Schiff base reaction.

PMID- 25778107
TI  - Thyroid function abnormalities associated with ponatinib therapy in patients with
      chronic myeloid leukemia.

PMID- 25778106
TI  - EjAP2-1, an AP2/ERF gene, is a novel regulator of fruit lignification induced by
      chilling injury, via interaction with EjMYB transcription factors.
AB  - Lignin biosynthesis is regulated by many transcription factors, such as those of
      the MYB and NAC families. However, the roles of AP2/ERF transcription factors in
      lignin biosynthesis have been rarely investigated. Eighteen EjAP2/ERF genes were
      isolated from loquat fruit (Eriobotrya japonica), which undergoes postharvest
      lignification during low temperature storage. Among these, expression of EjAP2-1,
      a transcriptional repressor, was negatively correlated with fruit lignification.
      The dual-luciferase assay indicated that EjAP2-1 could trans-repress activities
      of promoters of lignin biosynthesis genes from both Arabidopsis and loquat.
      However, EjAP2-1 did not interact with the target promoters (Ej4CL1). Yeast two
      hybrid (Y2H) and bimolecular fluorescence complementation (BiFC) assays indicated
      protein-protein interactions between EjAP2-1 and lignin biosynthesis-related
      EjMYB1 and EjMYB2. Furthermore, repression effects on the Ej4CL1 promoter were
      observed with the combination of EjAP2-1 and EjMYB1 or EjMYB2, while EjAP2-1 with
      the EAR motif mutated (mEjAP2-1) lost such repression, although mEjAP2-1 still
      interacted with EjMYB protein. Based on these results, it is proposed that EjAP2
      1 is an indirect transcriptional repressor on lignin biosynthesis, and the
      repression effects were manifested by EAR motifs and were conducted via protein
      protein interaction with EjMYBs.

PMID- 25778108
TI  - CFTR regulates acute inflammatory responses in macrophages.
AB  - BACKGROUND: Mutation of cystic fibrosis transmembrane conductance regulator
      (CFTR) in the airway epithelial cells can lead to recurrent airway inflammation
      in cystic fibrosis (CF). Dysfunction of CFTR in neutrophils could contribute to
      LPS-induced acute lung inflammation. Deficiency of CFTR could also facilitate
      platelet aggregation and neutrophil-platelet interaction and promote
      inflammation. AIM: To study whether inhibition or mutation of CFTR in alveolar
      macrophages (AMs) or peritoneal macrophages (PMs) would promote their
      proinflammatory responses and whether dysfunction of CFTR would deteriorate acute
      E. coli-induced lung or peritoneal inflammation. DESIGN: Laboratory study.
      METHODS: ELISA was used to determine production of proinflammatory cytokines in
      the CFTR inhibited or mutated macrophages under LPS challenge. Lung or peritoneum
      lavage was used to analyze proinflammatory parameters and cell differentiation.
      Excess lung water and lung vascular permeability were measured for evaluating
      severity of acute lung inflammation. RESULTS: Escherichia coli LPS simulation in
      AMs increased CFTR expression. Inhibition or mutation of CFTR in both AMs and PMs
      enhanced production of tumor necrosis factor alpha (TNF-alpha) and macrophage
      inflammatory protein-2 (MIP-2). Mutation of CFTR in macrophages exaggerated
      production of cytokines through NF-kB and p38 MAPK. Inhibition of CFTR by MalH2
      or CFTRinh-172 deteriorates E. coli-induced acute lung inflammation. Deficiency
      of CFTR promotes migration of monocytes and neutrophils in E. coli pneumonia and
      peritonitis mouse models. CONCLUSIONS: CFTR expressed by alveolar or peritoneal
      macrophages regulates acute proinflammatory responses.

PMID- 25778109
TI  - Association of the clinical frailty scale with hospital outcomes.
AB  - BACKGROUND: The clinical frailty scale (CFS) was validated as a predictor of
      adverse outcomes in community-dwelling older people. In our hospital, the use of
      the CFS in emergency admissions of people aged >= 75 years was introduced under
      the Commissioning for Quality and Innovation payment framework. AIM: We
      retrospectively studied the association of the CFS with patient characteristics
      and outcomes. DESIGN: Retrospective observational study in a large tertiary
      university National Health Service hospital in UK. METHODS: The CFS was
      correlated with transfer to specialist Geriatric ward, length of stay (LOS), in
      patient mortality and 30-day readmission rate. RESULTS: Between 1st August 2013
      and 31st July 2014, there were 11 271 emergency admission episodes of people aged
      >= 75 years (all specialties), corresponding to 7532 unique patients (first
      admissions); of those, 5764 had the CFS measured by the admitting team (81% of
      them within 72 hr of admission). After adjustment for age, gender, Charlson
      comorbidity index and history of dementia and/or current cognitive concern, the
      CFS was an independent predictor of in-patient mortality [odds ratio (OR) = 1.60,
      95% confidence interval (CI): 1.48 to 1.74, P < 0.001], transfer to Geriatric
      ward (OR = 1.33, 95% CI: 1.24 to 1.42, P < 0.001) and LOS >= 10 days (OR = 1.19,
      95% CI: 1.14 to 1.23, P < 0.001). The CFS was not a multivariate predictor of 30
      day readmission. CONCLUSIONS: The CFS may help predict in-patient mortality and
      target specialist geriatric resources within the hospital. Usual hospital metrics
      such as mortality and LOS should take into account measurable patient complexity.

PMID- 25778110
TI  - Relatives' and staff's experience of patients dying in ICU.
AB  - BACKGROUND: Intensive care units (ICUs) exist to support patients through acute
      illness that threatens their life. Although ICUs aim to save life, they are also
      a place where a significant proportion of patients die with international
      mortality rates ranging from 15% to 24%. AIM: To explore the experience of
      relatives and staff of patients dying in ICU using qualitative approach. DESIGN:
      Consecutive patients were identified who were dying in the ICU. The researcher
      met the families prior to the patient's death. The ICU nurse and doctor most
      involved were interviewed within 48 h of the death. The families were interviewed
      2 weeks later. Interviewees described their experience of the patient's dying and
      death. Recruitment until data saturation and thematic analysis occurred
      concurrently. RESULTS: Ten families, nurses and doctors were interviewed in
      relation to 10 patients. In caring for the patients who are dying in the ICU and
      their families, nurses practice to their satisfaction with creativity and
      autonomy, although concerned about continuity of care at handover. Families
      appreciate kindness and regular sensitive communication. Families would like more
      contact with the ICU doctors. Limiting access to the patient according to ICU
      protocol is distressing for relatives. Doctors struggle with decision making,
      determining prognosis and witnessing the grief of relatives. Some doctors wish to
      have a greater part in care of the dying patient. CONCLUSION: Distress among
      nurses reported in the ICU literature and attributed to disenfranchisement by
      doctors was not evident. In contrast, some doctors struggle to practice what they
      value. Adherence to ICU protocols needs flexibility when a patient is dying.

PMID- 25778111
TI  - Associations between workplace factors and carpal tunnel syndrome: A multi-site
      cross sectional study.
AB  - BACKGROUND: Few large epidemiologic studies have used rigorous case criteria,
      individual-level exposure measurements, and appropriate control for confounders
      to examine associations between workplace psychosocial and biomechanical factors
      and carpal tunnel syndrome (CTS). METHODS: Pooling data from five independent
      research studies, we assessed associations between prevalent CTS and personal,
      work psychosocial, and biomechanical factors while adjusting for confounders
      using multivariable logistic regression. RESULTS: Prevalent CTS was associated
      with personal factors of older age, obesity, female sex, medical conditions,
      previous distal upper extremity disorders, workplace measures of peak forceful
      hand activity, a composite measure of force and repetition (ACGIH Threshold Limit
      Value for Hand Activity Level), and hand vibration. CONCLUSIONS: In this cross
      sectional analysis of production and service workers, CTS prevalence was
      associated with workplace and biomechanical factors. The findings were similar to
      those from a prospective analysis of the same cohort with differences that may be
      due to recall bias and other factors.

PMID- 25778112
TI  - Magnetic Resonance Imaging-Assessed Vastus Medialis Muscle Fat Content and Risk
      for Knee Osteoarthritis Progression: Relevance From a Clinical Trial.
AB  - OBJECTIVE: Studies have proposed vastus medialis (VM) muscle cross-sectional area
      change as a variable associated with cartilage volume loss in knee osteoarthritis
      (OA). However, the VM also includes fat (%Fat), which may influence knee
      function. This study analyzed the VM area and %Fat data, separately and in
      combination, to predict symptoms, cartilage volume loss, and bone marrow lesion
      (BML) change in knee OA. METHODS: This study included the according-to-protocol
      population (n = 143) of a 2-year knee OA randomized clinical trial having
      magnetic resonance imaging at baseline and 2 years. Correlations used
      multivariate analyses. RESULTS: Greater baseline value for VM area and %Fat were
      significantly associated with sex (male, area; female, %Fat), higher body mass
      index (BMI), and Western Ontario and McMaster Universities Osteoarthritis Index
      stiffness, function, and total scores (better, high area; worse, high %Fat).
      Moreover, a VM %Fat increase of 1% at 2 years was associated with worsening of
      cartilage volume loss in the global knee (P = 0.015) and some subregions (P <=
      0.030), and with an increment of BML global score change (P < 0.001). A 1%
      decrease in VM area at 2 years was associated with worsening of knee pain score
      (P = 0.048). Importantly, the concurrent presence of low VM area, high VM %Fat,
      and high BMI identified a subgroup of patients with greater cartilage volume loss
      in the medial femur (P = 0.028) than the rest of the cohort. CONCLUSION: These
      data demonstrated, for the first time, that VM fat content is a strong predictor
      of cartilage volume loss and the occurrence and progression of BML. Importantly,
      the combined data of VM area, VM %Fat, and BMI identified patients at higher risk
      for OA progression.

PMID- 25778282
TI  - High levels of contamination and antimicrobial-resistant non-typhoidal Salmonella
      serovars on pig and poultry farms in the Mekong Delta of Vietnam.
AB  - We investigated the prevalence, diversity, and antimicrobial resistance (AMR)
      profiles of non-typhoidal Salmonella (NTS) and associated risk factors on 341
      pig, chicken, and duck farms in Dong Thap province (Mekong Delta, Vietnam).
      Sampling was stratified by species, district (four categories), and farm size
      (three categories). Pooled faeces, collected using boot swabs, were tested using
      ISO 6575: 2002 (Annex D). Isolates were serogrouped; group B isolates were tested
      by polymerase chain reaction to detect S. Typhimurium and (monophasic) serovar
      4,[5],12:i:- variants. The farm-level adjusted NTS prevalence was 64.7%, 94.3%
      and 91.3% for chicken, duck and pig farms, respectively. Factors independently
      associated with NTS were duck farms [odds ratio (OR) 21.2], farm with >50 pigs
      (OR 11.9), pig farm with 5-50 pigs (OR 4.88) (vs. chickens), and frequent rodent
      sightings (OR 2.3). Both S. Typhimurium and monophasic S. Typhimurium were more
      common in duck farms. Isolates had a high prevalence of resistance (77.6%)
      against tetracycline, moderate resistance (20-30%) against chloramphenicol,
      sulfamethoxazole-trimethoprim, ampicillin and nalidixic acid, and low resistance
      (<5%) against ciprofloxacin and third-generation cephalosporins. Multidrug
      resistance (resistance against ?3 classes of antimicrobial) was independently
      associated with monophasic S. Typhimurium and other group B isolates (excluding
      S. Typhimurium) and pig farms. The unusually high prevalence of NTS on Mekong
      Delta farms poses formidable challenges for control.

PMID- 25778284
TI  - An Unusual Case of Complete AV Block.

PMID- 25778283
TI  - Effect of white, red and black ginseng on physicochemical properties and
      ginsenosides.
AB  - A systematic comparison of the ginsenosides and physicochemical properties of
      white ginseng (WG), red ginseng (RG) and black ginseng (BG) was performed. The
      purpose of the present study was to identify the effects of the physicochemical
      properties by steaming process. During the steaming process, ginsenosides
      transform into specific ginsenosides by hydrolysis, dehydration and isomerization
      at C-3, C-6 or C-20. Steaming ginseng led to a significant increase in reducing
      sugar, acidic polysaccharide and phenolic compounds content. Antioxidative
      properties were investigated using the DPPH (2,2-diphenyl-1-picrylhydrazyl)
      radical scavenging activity, compared with BHA (Butylated hydroxyanisole). RG and
      BG exhibited higher antioxidant activity than WG. The maximum residue level for
      Benzo(a)pyrene was established to 5 MUg/kg in food products. The levels of
      benzo(a)pyrene in WG and RG were not detected. Benzo(a)pyrene was detected in the
      BG, the content was 0.17 MUg/kg. The scientific achievements of the present study
      could help consumers to choose different type of ginseng products available on
      the market.

PMID- 25778286
TI  - Effect of irrigation regime on anthocyanin content and antioxidant activity of
      Vitis vinifera L. cv. Syrah grapes under semiarid conditions.
AB  - BACKGROUND: Irrigation management is a powerful technique to control grape and
      wine colour. However, water deficit effects on anthocyanins are often
      contrasting, depending on the severity of water restriction. In addition, the
      effect of irrigation on the antiradical capacity of grapes has not been
      extensively studied. In this work the effect of water availability on anthocyanin
      profile and content as well as the antioxidant activity of Syrah grapes was
      investigated in an irrigation trial under semiarid climate conditions. RESULTS:
      Three irrigation treatments were applied in a 15-year-old Vitis vinifera cv.
      Syrah vineyard, starting at berry set through harvest of 2011 and 2012: full
      irrigation (FI) at 100% of crop evapotranspiration (ETc), deficit irrigation (DI)
      at 50% of ETc and non-irrigated (NI). NI grapes were characterized by increased
      individual anthocyanin content. However, differences among irrigation treatments
      were significant only around 18-24 days after veraison, when anthocyanin
      accumulation was maximum. The antioxidant activity of the skin extracts was not
      affected by irrigation. CONCLUSION: Irrigation proved to be an effective
      technique to control anthocyanin content in Syrah grapes under semiarid
      conditions. However, anthocyanin accumulation pattern should be considered by
      winemakers to appropriately select harvest time for improved wine colour.

PMID- 25778285
TI  - Biocompatibility of poly(ethylene glycol) and poly(acrylic acid) interpenetrating
      network hydrogel by intrastromal implantation in rabbit cornea.
AB  - We evaluated the biocompatibility of a poly(ethylene glycol) and poly(acrylic
      acid) (PEG/PAA) interpenetrating network hydrogel designed for artificial cornea
      in a rabbit model. PEG/PAA hydrogel measuring 6 mm in diameter was implanted in
      the corneal stroma of twelve rabbits. Stromal flaps were created with a
      microkeratome. Randomly, six rabbits were assigned to bear the implant for 2
      months, two rabbits for 6 months, two rabbits for 9 months, one rabbit for 12
      months, and one rabbit for 16 months. Rabbits were evaluated monthly. After the
      assigned period, eyes were enucleated, and corneas were processed for histology
      and immunohistochemistry. There were clear corneas in three of six rabbits that
      had implantation of hydrogel for 2 months. In the six rabbits with implant for 6
      months or longer, the corneas remained clear in four. There was a high rate of
      epithelial defect and corneal thinning in these six rabbits. One planned 9-month
      rabbit developed extrusion of implant at 4 months. The cornea remained clear in
      the 16-month rabbit but histology revealed epithelial in-growth. Intrastromal
      implantation of PEG/PAA resulted in a high rate of long-term complications.

PMID- 25778287
TI  - Trajectories of cognitive function in dementia-free subjects: Radiation Effects
      Research Foundation Adult Health Study.
AB  - OBJECTIVES: To investigate associations between age, sex, education, and birth
      cohort and global cognitive decline among a population that would most likely not
      progress to dementia. METHODS: A total of 1538 dementia-free subjects aged 60 to
      80years in 1992 were followed up through 2011 without dementia occurrence. We
      assessed cognitive function using the Cognitive Ability Screening Instrument
      (CASI). Using stepwise-like model selection procedure, we built mixed-effects
      models for initial cognition and longitudinal cognition. RESULTS: Initial CASI
      scores for younger age and more years of formal education were higher than those
      for older and less education. Sex did not show a significant effect. In the
      longitudinal analysis, cognitive decline became more rapid with increasing age.
      Sex and education did not modify the degree of deterioration with age. CASI
      scores were higher for younger cohorts and men due to differences in education
      levels. CONCLUSION: Among dementia-free subjects, age is an important predictor
      of cognitive function level and cognitive decline. Education level affects
      cognitive function level, but did not affect cognitive decline. The results have
      implications not only for elucidation of the aging process, but also for
      reference in dementia screening.

PMID- 25778288
TI  - In search for better pharmacological prophylaxis for acute mountain sickness:
      looking in other directions.
AB  - Despite decades of research, the exact pathogenic mechanisms underlying acute
      mountain sickness (AMS) are still poorly understood. This fact frustrates the
      search for novel pharmacological prophylaxis for AMS. The prevailing view is that
      AMS results from an insufficient physiological response to hypoxia and that
      prophylaxis should aim at stimulating the response. Starting off from the
      opposite hypothesis that AMS may be caused by an initial excessive response to
      hypoxia, we suggest that directly or indirectly blunting-specific parts of the
      response might provide promising research alternatives. This reasoning is based
      on the observations that (i) humans, once acclimatized, can climb Mt Everest
      experiencing arterial partial oxygen pressures (PaO2) as low as 25 mmHg without
      AMS symptoms; (ii) paradoxically, AMS usually develops at much higher PaO2
      levels; and (iii) several biomarkers, suggesting initial activation of specific
      pathways at such PaO2, are correlated with AMS. Apart from looking for substances
      that stimulate certain hypoxia triggered effects, such as the ventilatory
      response to hypoxia, we suggest to also investigate pharmacological means aiming
      at blunting certain other specific hypoxia-activated pathways, or stimulating
      their agonists, in the quest for better pharmacological prophylaxis for AMS.

PMID- 25778289
TI  - Parasporins as new natural anticancer agents: a review.
AB  - In 1999 Mizuki and co-authors studied for the first time the parasporal inclusion
      proteins extracted from B. thuringiensis strains (a Gram-positive, soil-dwelling
      bacterium) for cytotoxic activity against human leukaemia T-cells. Later some
      other proteins with this unusual property to recognize human leukemic cells were
      isolated from this strain of bacteria and named parasporins. At present 6 types
      of parasporins are identified and characterized. This review summarizes the
      properties of these new potentially useful antitumor agents of natural origin.
      Various types of parasporins possess unique cytotoxic mechanisms against cancer
      cells. The cytotoxic activity for cancer cells makes parasporins possible
      candidates for anticancer agents in clinical oncology. Recently, genetic
      engineering was applied for the production of parasporins and the gene
      responsible for the production of the proteins was expressed in E. coli. However,
      there are virtually no data regarding the cytotoxic (antitumor) activity of
      parasporins in vivo. These relatively new cytotoxic proteins warrant further
      investigation, especially in rodents, for possible application in clinical
      oncology. 

PMID- 25778290
TI  - Fighting against human papillomavirus: the 25-year old contribution of the
      University of Crete School of Medicine.
AB  - Twenty five years have passed since the first research efforts in Greece on human
      papillomavirus (HPV) performed by the Department of Clinical Virology at the
      University of Crete School of Medicine. HPV infection in the human cervix was
      initially evaluated in relation to the host mutational and transcriptional
      activation of the ras/raf genes pathway, p53 gene polymorphisms, neo-angiogenesis
      related gene expression and G1/S phase transition. A series of epidemiological
      studies ensued, evaluating HPV infection in the ophthalmic pterygium, benign
      laryngeal tumors, parotid lesions, nasal polyposis, actinic keratosis, aborted
      material and non-genital cancers. The observed geographical variations of
      different HPV types within the Hellenic population indicated a higher prevalence
      of HPV 18 on the island of Crete compared to mainland Greece. Moreover, our
      research led to the investigation of the mother-to-infant HPV transmission via
      human breast milk and the detection of novel HPV types in juvenile recurrent
      respiratory papillomatosis. We also evaluated the presence of HPV in the
      respiratory tract of asymptomatic children and the relationship between maternal
      HPV infection and neonatal prematurity. Despite the introduction of the current
      prophylactic vaccines against HPV into clinical practice, HPV remains a
      challenging target for the next generation of researchers, as the war against HPV
      continues. 

PMID- 25778291
TI  - A retrospective analysis of adjuvant CAF, AC-T and TAC regimens in triple
      negative early stage breast cancer.
AB  - PURPOSE: To compare the effectiveness of adjuvant chemotherapy regimens in triple
      negative breast cancer (TNBC) for which no protocol has been determined to be
      treatment of choice. METHODS: In this single-center retrospective trial, we
      analyzed the adjuvant regimens of 164 TNBC patients among 3253 breast cancer
      patient records. Adjuvant TAC (docetaxel, doxorubicin, cyclophosphamide), CAF
      (cyclophosphamide, doxorubicin, 5fluorouracil), and AC-T (doxorubicin,
      cyclophosphamide followed by docetaxel) regimens were compared in terms of
      disease free survival (DFS) and overall survival (OS). RESULTS: In terms of both
      DFS and OS TAC was significantly superior to AC-T in node positive TNBC. When
      node negative and positive patients were analyzed together, TAC was still
      significantly superior to AC-T in terms of DFS and OS. There was a trend favoring
      CAF over AC-T, however, it was only significant in terms of OS when all node
      negative and positive TNBC patients were incorporated together. CONCLUSION: In
      the adjuvant setting, especially in node positive patients, TAC should be the
      treatment of choice in TNBC patients. CAF is probably better than AC-T in TNBC.

PMID- 25778292
TI  - Progesterone receptor status in determining the prognosis of estrogen receptor
      positive/ HER2 negative breast carcinoma patients.
AB  - PURPOSE: To evaluate the impact of progesterone receptor (PR) status on estrogen
      receptor (ER)-positive and HER2-negative breast cancer. METHODS: A total of 1673
      operable breast cancer patients, diagnosed from June 1984 to June 2011 were
      retrospectively reviewed and 400 patients with ER-positive and HER2-negative
      tumors were identified and evaluated. ER-positive and HER2-negative patients were
      classified into two groups: group A: ER+/PR-/HER2- and group B : ER+/PR+/HER2-
      according to PR status. RESULTS: Median follow-up was 14.2 years (range 10.1
      18.2). The ratio of postmenopausal patients was significantly higher in group A
      (68.2%, p=0.015). Grade 1 tumor and stage I disease were significantly higher in
      group B (15%, p=0.007 and 15%, p=0.005, respectively). Mean overall survival (OS)
      and disease free survival (DFS) were significantly better in group B (15.3+/-1.5
      years vs 8.7+/-0.8 years, p=0.032; 10.5+/-1.6 years vs 5.7+/-0.5 years, p=0.022)
      as compared with group A. Relative risk for recurrence and death were two-fold
      higher in group A (p=0.05 and p=0.01, respectively). CONCLUSION: PR status exerts
      a significant impact on prognosis of ER+/HER2- breast cancer.

PMID- 25778294
TI  - Analysis of the cytological features supporting the diagnosis of lobular breast
      cancer. Factors associated with equivocal diagnoses.
AB  - PURPOSE: Lobular carcinoma, the second most frequent type of breast cancer,
      accounts for 8-14% of all invasive breast cancers and presents a wide spectrum of
      differences from tumors of ductal origin. Its cytomorphologic features can create
      diagnostic problems. The purpose of this study was to identify the cytological
      and immunocytological features that support the diagnosis of lobular breast
      cancer. METHODS: We retrospectively reviewed and analyzed a series of 46 fine
      needle aspirates (FNA) of invasive lobular carcinomas confirmed
      histopathologically. All findings were classified and analyzed in order to
      identify possible sources of diagnostic failure. RESULTS: Mammographic features
      were very subtle in most cases. The detailed cytomorphologic analysis revealed
      mainly discohesive architecture (95%), little or no nuclear atypia (91.3%),
      smooth regular nuclear membrane (93.47%) and low mitotic rate (97.8%). Loss of E
      Cadherin immunoexpression was found in all cases. Estrogen (ER) and progesterone
      (PR) receptors were positive in the majority of the cases, whereas C-erbB2
      (HER2/neu) was negative. CONCLUSION: Discohesive architecture, low grade of
      nuclear atypia and plasmatoid appearance were the most important features .The
      correct preoperative diagnosis of lobular carcinoma permits a more specialized
      therapeutic approach.

PMID- 25778293
TI  - Molecular subtypes in patients with inflammatory breast cancer; a single center
      experience.
AB  - PURPOSE: The purpose of this study was to investigate the frequency and prognosis
      of inflammatory breast cancer (IBC) according to molecular subtypes. METHODS:
      Demographic data were examined for 78 patients diagnosed with IBC among breast
      cancer patients monitored in our clinic. Patients were staged according to the
      2010 AJCC guidelines. Physical examination and radiographic findings classified
      on the basis of Response Evaluation Criteria in Solid Tumors (RECIST) guidelines
      were employed in the evaluation of clinical response to systemic therapy. Subtype
      analysis was performed in patients with IBC and subtypes were compared. Patients
      were divided on the basis of metastatic or non metastatic status and survival
      analysis was performed on the basis of molecular subtypes. RESULTS: Distribution
      analysis of molecular subtypes revealed a lower incidence of luminal A and a
      higher incidence of both HER 2 (+) and triple negative breast cancer in IBC.
      Molecular subtypes had no effect on survival in the non metastatic (p=0.61) and
      metastatic patient group (p=0.08). CONCLUSION: This study showed that IBC
      frequency is higher in HER2 overexpressing and triple negative subtypes. No
      survival differences were noticed in relation to molecular subtypes in IBC
      patients.

PMID- 25778295
TI  - Neoadjuvant chemotherapy-induced changes in immunohistochemical expression of
      estrogen receptor, progesterone receptor, HER2, and Ki-67 in patients with breast
      cancer.
AB  - PURPOSE: The impact of neoadjuvant chemotherapy (NACT) on immunohistochemical
      markers in breast cancer specimens remains controversial. We designed the current
      study to investigate the potential changes in estrogen receptor (ER),
      progesterone receptor (PR), HER2, and Ki-67 expression before and after NACT in a
      cohort of Turkish patients with breast cancer. METHODS: This research was
      designed as a prospective, observational study of 100 consecutive patients with
      breast cancer (mean age 47.8+/-11.4 years) who were scheduled to undergo
      anthracycline- and/or taxane-containing NACT before attempting cytoreductive
      surgery at the Department of Oncology of the Uludag University Medical Center,
      Bursa, Turkey. Immunohistochemistry was performed on formalin-fixed, paraffin
      embedded specimens. RESULTS: Changes in immunohistochemical markers before and
      after NACT were only significant for HER-2 and Ki- 67. More specifically, the
      number of HER-2-positive specimens decreased from 21 before NACT to 8 after NACT
      (p<0.001). Similarly, the number of tumor samples positive for Ki-67 decreased
      significantly from 65 to 24 after NACT (p<0.001). Mean pre- and post-treatment
      tumor grades of differentiation before and after NACT were 2.56 +/- 0.67 and
      2.37+/-1.07, respectively (p<0.05). We did not find any significant associations
      between baseline ER, PR, HER2, and Ki-67 expression with both overall survival
      (OS) and disease- free survival (DFS). CONCLUSION: Our study suggests that NACT
      reduces the expression of HER2 and Ki-67 in breast cancer specimens. The
      significance of NACT-induced changes in the immunohistochemical expression of
      HER2 and Ki-67 in patients with breast cancer should be further studied in future
      translational and clinical research.

PMID- 25778296
TI  - The effect of renin-angiotensin-system inhibition on survival and recurrence of
      N3+ breast cancer patients.
AB  - PURPOSE: The purpose of this study was to evaluate the association between the
      rennin-angiotensin system (RAS) inhibition and the risk of breast cancer (BC)
      recurrence and progression in N3 positive patients. METHODS: The medical records
      of patients treated for N3 positive BC in Hacettepe Cancer Institute between 2005
      and 2012 were evaluated. Angiotensin converting enzyme (ACE)
      inhibitors/angiotensin receptor blockers (ARB) users were defined as patients who
      took these medications for at least 6 months in no evidence of disease (NED)
      stage after the initial diagnosis. The primary and secondary outcome was disease
      free survival (DFS) and overall survival (OS). Kaplan-Meier and Cox proportional
      hazard models were used. RESULTS: A total of 218 pathologic N3 BC patients were
      included. Follow up ranged from 12 to 212 months (median 49.58). Thirty one
      patients used ACE inhibitors/ARBs. Univariate analysis showed BC recurrence was
      lower and OS was higher among patients who used ACE inhibitors/ ARBs, however
      without reaching statistical significance (p=0.38 and p=0.24, respectively). RAS
      inhibition was associated with reduced risk of pathologic N3 BC recurrence.
      CONCLUSION: To the best of our knowledge this is the second study showing that
      the use of ACE inhibitors/ARBs may be effective in N3 BC. Because of the limited
      therapeutic options in BC, new drugs or new therapeutic modalities should be
      considered. In the future, studies with long-term follow-up may be helpful for
      their implication in clinical practice.

PMID- 25778297
TI  - Mammary gland epithelial changes in thyroidectomized female rats.
AB  - PURPOSE: Numerous clinical studies have addressed the relationship of
      hypothyroidism and breast cancer with conflicting results. In the present
      experimental study we sought to determine whether absolute hypothyroidism
      established for a long period of time leads to epithelial alterations of the
      mammary gland. METHODS: Thirty five female Wistar rats were allocated to be
      subjected to either thyroidectomy (N=20) or not (N=15). The rats were kept alive
      for a period of 3 months in a weather controlled environment. Serum T3, T4,
      follicular stimulating hormone (FSH) and estradiol levels were measured at
      baseline and 10 days after thyroidectomy. Mammary glands were obtained at the end
      of the experiment and reviewed by an expert pathologist. RESULTS: Both serum FSH
      and estradiol levels were lower 10 days after thyroidectomy; however, only FSH
      values were significantly lower in the thyroidectomized animals. Pathological
      analysis revealed significantly increased atrophy and periductal fibrosis of the
      mammary gland among thyroidectomized animals. CONCLUSION: This is the first in
      vivo experimental study that reveals an association between the thyroid and
      mammary glands. Future studies should address the proteomic relationship that
      connects them.

PMID- 25778298
TI  - Magnetic resonance imaging in restaging rectal cancer after neoadjuvant
      chemoradiotherapy.
AB  - PURPOSE: To evaluate the accuracy of magnetic resonance imaging (MRI) for
      restaging locally advanced nonmucinous rectal cancer after neoadjuvant
      chemoradiotherapy (CRT). METHODS: A total of 94 consecutive patients with
      histologically proven locally advanced middle or low located nonmucinous rectal
      adenocarcinoma, who were treated with preoperative CRT, followed by radical
      surgery 6-8 weeks later, were analyzed in this retrospective study. Preoperative
      MR images were reinterpreted by one observer and the results were compared with
      the histologic findings. The overall MRI tumor (T) and nodal (N) restaging
      accuracy were calculated. The agreement between post-CRT MRI examination and
      histological assessment was evaluated by using kappa statistics. RESULTS: The
      overall accuracy of MRI for T restaging was 49%, with overstaging and
      understaging occurring in 40.4% and 10.6% of the patients, respectively. Only 18%
      of the patients with pathological complete response (pCR) were staged correctly
      by MRI, nevertheless an excellent 100% specificity in predicting pCR was
      detected. For N restaging with MRI, the overall accuracy was 63.8%, whereas 26.6%
      of the patients were overstaged and 9.6% were understaged. Kappa statistics
      revealed poor concordance of MRI restaging after preoperative CRT and
      pathological results in both T (k=0.156) and N staging (k=0.289). CONCLUSIONS:
      Restaging rectal cancer still remains a challenge and better methods are urgently
      required. The surgical plan before treatment should not be changed except in
      those cases who had pCR, intolerance or refusing radical operation, for whom an
      observation strategy could be taken into consideration after the excellent
      specificity in predicting pCR.

PMID- 25778299
TI  - Determinants of survival after liver resection for metastatic colorectal
      carcinoma.
AB  - PURPOSE: Prognostic factors for survival after liver resection for metastatic
      colorectal cancer identified up to date are quite inconsistent with a great inter
      study variability. In this study we aimed to identify predictors of outcome in
      our patient population. METHODS: A series of 70 consecutive patients from the
      oncological hepatobiliary database, who had undergone curative hepatic surgical
      resection for hepatic metastases of colorectal origin, operated between 2006 and
      2011, were identified. At 44.6 months (range 13.7-73), 30 of 70 patients (42.85%)
      were alive. Patient demographics, primary tumor and liver tumor factors,
      operative factors, pathologic findings, recurrence patterns, disease-free
      survival (DFS), overall survival (OS) and cancer-specific survival (CSS) were
      analyzed. Clinicopathologic variables were tested using univariate and
      multivariate analyses. RESULTS: The 3-year CSS after first hepatic resection was
      54%. Median CSS survival after first hepatic resection was 40.2 months. Median
      CSS after second hepatic resection was 24.2 months. The 3-year DFS after first
      hepatic resection was 14%. Median disease free survival after first hepatic
      resection was 18 months. The 3-year DFS after second hepatic resection was 27%
      and median DFS after second hepatic resection 12 months. The 30-day mortality and
      morbidity rate after first hepatic resection was 5.71% and 12.78%, respectively.
      In univariate analysis CSS was significantly reduced for the following factors:
      age >53 years, advanced T stage of primary tumor, moderately- poorly
      differentiated tumor, positive and narrow resection margin, preoperative CEA
      level >30 ng/ml, DFS <18 months. Perioperative chemotherapy related to
      metastasectomy showed a trend in improving CSS (p=0.07). Perioperative
      chemotherapy improved DFS in a statistically significant way (p=0.03).
      Perioperative chemotherapy and achievement of resection margins beyond 1 mm were
      the major determinants of both CSS and DFS after first liver resection in
      multivariate analysis. CONCLUSIONS: In our series predictors of outcome in
      multivariate analysis were resection margins beyond 1mm and perioperative
      chemotherapy. Studies on larger population and analyses of additional
      clinicopathologic factors like genetic markers could contribute to development of
      clinical scoring models to assess the risk of relapse and survival.

PMID- 25778300
TI  - High levels of platelet/lymphocyte ratio are associated with metastatic gastric
      cancer.
AB  - PURPOSE: The predictive and prognostic value of cheap, easily accessible and
      commonly available complete blood count parameters has already been studied in a
      variety of cancers. In the present study, we aimed to investigate the association
      between pretreatment platelet/lymphocyte ratio (PLR) and metastatic gastric
      cancer. METHODS: The records of 228 patients dating from January 2010 to June
      2014 were retrospectively evaluated. Patients who had undergone radical (N=157)
      or palliative gastrectomy (N=71) for metastatic gastric cancer were included and
      divided into two groups according to stage (early-advanced) and metastasis
      (absence-presence) status, and PLR values were compared. RESULTS: 38 (16.6%) of
      228 patients had early gastric cancer (non metastatic cases). PLR values of
      advanced gastric cancer (not including metastatic cases) were significantly
      higher compared to early gastric cancer (231.6+/-107.45 and 160.3+/-71.5,
      respectively; p<0.001). Seventy one (31.1%) of 228 patients had distant
      metastasis. PLR values of metastatic gastric cancer were significantly higher
      than in non-metastatic gastric cancer (251.0+/-94.8 and 192.7+/-88.8,
      respectively; p<0.001). Logistic regression analysis showed that PLR was an
      independent predictive factor for tumor burden in both stage and metastasis
      groups (p<0.001 and p=0.003, respectively). Also, in correlation analysis, PLR
      showed mild correlation with stage and metastasis groups (r=0.291 and r=0.299,
      respectively). CONCLUSIONS: Pretreatment PLR values were correlated with tumor
      burden, and most higher values were detected in metastatic disease. Our findings
      may be useful, especially in the decision-making for laparoscopic staging in
      patients who have no radiological evidence of metastatic disease.

PMID- 25778301
TI  - Augmenter of liver regeneration gene expression in human colon cancer cell lines
      and clinical tissue samples.
AB  - PURPOSE: Augmenter of liver regeneration (ALR) is an hepatotrophic factor
      responsible for the increased regenerative capacity of mammalian liver and ALR
      gene expression has been well-documented in liver cirrhosis and hepatocellular
      carcinoma tissue samples. The present study aimed to quantify and evaluate ALR
      gene expression in human colon cancer cell lines and tissue samples. METHODS:
      Total RNA was isolated from 6 colorectal cancer cell lines and 23 primary
      colorectal tumors, cDNA was prepared and ALR mRNA expression analysis was
      performed using quantitative real-time PCR. RESULTS: ALR mRNA expression was
      confirmed in all 6 colorectal cancer cell lines (SW480, SW620, DLD-1, RKO, COLO
      205 and HTC-116) and an epithelial one (WISH). DLD-1 cell line showed the highest
      ALR mRNA levels, followed by RKO, COLO-205, HCT-116, SW480, SW620 and WISH cell
      lines. ALR gene expression levels were detected in all cancer tissue samples
      (N=23), being significantly increased in well/moderately compared to poorly
      differentiated tumors (p=0.0208). ALR gene expression levels were increased in
      Dukes' stage A/B compared to stage C tumors, at a non significant level
      (p=0.2842). ALR mRNA levels were slightly higher in colon cancer tissues compared
      to adjacent non-neoplastic ones (N=19), at a non significant level (p=0.2122).
      CONCLUSION: The present study verified for the first time the ALR gene expression
      in both human colon cancer cell lines and clinical samples. Enhanced ALR gene
      expression was negatively correlated with advanced histopathological grade and
      stage in both colon cancer cell lines and human tissue samples, implicating ALR
      participation at the early stage of colon malignant progression.

PMID- 25778302
TI  - Evaluation of clinical, morphopathological and therapeutic prognostic factors in
      rectal cancer. Experience of a tertiary oncology center.
AB  - PURPOSE: Morphopathological factors continue to be the most important prognostic
      factors in colorectal cancer, but there is evidence regarding the prognostic
      value of some factors that are not yet used in current clinical practice. The
      purpose of the present study was to evaluate the most important clinical,
      morphopathological and therapeutic prognostic factors in rectal cancer. METHODS:
      This study retrospectively analyzed 317 patients diagnosed and treated at the Ion
      Chiricuta Institute of Oncology between 2000-2008. The prognostic value of 13
      variables was analyzed and correlations between them were established. Nine
      variables were included in a multivariate analysis model. RESULTS: The 5-year
      overall survival (OS) was 55.6%, significantly higher for patients with TNM stage
      I disease 7l.7%), compared to stage II (71.4%), stage III (45.4%) and stage IV
      (12.5%; p<0.001). In multivariate analysis, the independent prognostic factors
      were tumor stage, age, lymph node invasion, venous, lymphatic and perineural
      invasion. CONCLUSIONS: In addition to the TNM stage and lymph node invasion, age,
      venous, lymphatic and perineural invasion were also proved to have prognostic
      significance in rectal cancer. Further studies are required for the validation of
      prognostic assessment models in patients diagnosed with rectal cancer.

PMID- 25778303
TI  - Involvement of leptin receptors expression in proliferation and neoangiogenesis
      in colorectal carcinoma.
AB  - PURPOSE: This study tested whether there exists a correlation between leptin
      receptors (LEPR) expression with proliferation and neoangiogenesis in colorectal
      carcinoma. METHODS: Enrolled were 75 patients with colorectal carcinoma, who
      underwent surgical tumor resection. After routine histopathological preparation,
      sections 3-4 MUm thick were prepared. Routine H&E and immunohistochemical ABC
      method with anti-LEPR, anti-Ki67 and anti-CD 105 antibodies were performed.
      RESULTS: Pronounced or moderate LEPR expression in colorectal carcinoma was found
      in 77.3% of the cases. Absence of expression of LEPR correlated with low rate of
      proliferation in 94.1% of the cases, while high proliferation rate showed 92% of
      the cases with pronounced LEPR expression. Low grade neoangiogenesis correlated
      with absence of LEPR expression in 88.2% of the cases. In 92% of the cases with
      pronounced LEPR expression, high rate of angiogenesis was observed. The LEPR
      expression correlated significantly (p<0.001) with proliferation index (proIDX)
      and neoangiogenesis index (mvdIDX). The corresponded correlation coefficients
      indicated considerable strength of association between variables (r=0.63 and
      r=0.66). CONCLUSION: Our results demonstrated that LEPR expression in colorectal
      carcinoma significantly corresponded to proliferation index of tumor cells and
      neoangiogenesis, which could have significant therapeutic and prognostic
      implications.

PMID- 25778304
TI  - Meta analysis of the association of cholesterol with pancreatic carcinoma risk.
AB  - PURPOSE: Pancreatic carcinoma is a malignant tumor with poor prognosis. This
      metaanalysis was conducted to investigate if there exists any association of
      cholesterol with pancreatic carcinoma risk. METHODS: A literature search was
      performed in Cochrane Central Library, PubMed, MEDLINE, EMBASE, CNKI (China
      National Knowledge Infrastructure), China Biology Medical literature database
      (CBM), and WangFang database for relevant available articles. Dietary cholesterol
      and serum levels of total cholesterol (TC) were assessed and compared. Pooled
      relative risks (RRs) with 95% confidence intervals (CIs) were calculated.
      RESULTS: A total 19 articles coming from Europe, Asia and north America were
      assessed in this study. There was a significant difference between highest and
      lowest dietary cholesterol intake for pancreatic carcinoma risk (RR=1.31, 95%
      CI:1.10 to 1.56, p=0.01). Moreover, in subgroup analysis, there was a significant
      difference between highest and lowest dietary cholesterol intake for pancreatic
      carcinoma risk for case-control studies (RR=1.52, 95% CI:1.23 to 1.90, p=0.04).
      However, no significant difference was noticed between highest and lowest dietary
      cholesterol intake for pancreatic carcinoma risk for cohort studies (RR=1.02, 95%
      CI:0.87 to 1.20, p=0.51). The meta analysis results showed a significant
      difference between highest and lowest dietary cholesterol for pancreatic
      carcinoma in Europeans (RR=1.15, 95% CI:0.86 to 1.53, p=0.05). Moreover, compared
      to the low serum level of TC, the high level serum TC was associated with
      pancreatic carcinoma risk (RR=1.00, 95% CI:0.86-1.17, p=0.03). There was a
      significant difference between high and low levels of serum TC for pancreatic
      carcinoma risk in Europeans (RR=1.03, 95% CI: 0.72 to 1.48, p=0.04). CONCLUSION:
      Dietary or serum cholesterol may be associated with risk for increased pancreatic
      carcinoma.

PMID- 25778305
TI  - The prognostic value of FOXP3+ T regulatory cells in colorectal cancer.
AB  - PURPOSE: The evaluation of CD3(+) T-cell density is believed to have a higher
      prognostic value than the conventionally used TMN stage in colorectal cancer
      (CRC), but the role of regulatory T lymphocytes (Treg) is still debated. Our
      study determined the prognostic value of forkhead box P3 nuclear transcription
      factor (FOXP3) positive Treg and CD3(+) T-cells in the invasive margin of CRC
      compared with other known prognostic factors. METHODS: The prognostic factors
      analysed in 42 patients with CRC stage II (N=13) and III (N=29), were age, tumor
      location, TNM stage, histological grade, vascular, lymphatic and perineural
      invasion. CD3(+) T-cells and FOXP3(+) Treg density was evaluated by
      immunohistochemistry. RESULTS: The median CD3(+) T-cells and FOXP3(+) Treg
      density was 438.93/mm(2) and 162.25/mm(2), respectively. Patients with high
      FOXP3(+) Treg density showed improved 5-year survival rate of 89.41%, compared
      with 64.6% of those with low density (p=0.024). CONCLUSIONS: Increased CD3(+) T
      cells and FOXP3(+) Treg density is associated with improved survival, but only
      the latter proved to be an independent prognostic factor. FOXP3(+) Treg
      infiltrate may play an important prognostic role, which, in combination with
      other predictive factors, could lead to the development of specific treatment
      regimens.

PMID- 25778306
TI  - The proinflammatory effect and molecular mechanism of IL- 17 in the intestinal
      epithelial cell line HT-29.
AB  - PURPOSE: To evaluate the proinflammatory effect and molecular mechanism of IL-17
      in the intestinal epithelial cell line HT-29. METHODS: After culture of HT-29
      cells with IL-17 and/or TNF-(alpha), real-time (RT) PCR and Western blot were
      used to measure the gene expression level of the neutrophil chemokines CXCL1,
      CXCL2, CXCL5, CXCL6, IL-8 and the Th-17 chemokine CCL20, the phosphorylation
      level of P38 and TNF-alpha, and the expression level of IL-8 after treatment with
      P38 inhibitor. Act1 stable knockdown HT-29 cell line was established to further
      test the change of P38 phosphorylation after treatment with IL-17 and TNF-alpha.
      RESULTS: When HT-29 cells were cultured with IL-17 and TNF-alpha, the expression
      level of neutrophil chemokines (CXCL1, CXCL2, CXCL5, CXCL6, IL-8) and Th17
      chemokine (CCL20) was significantly improved (24.96+/-2.53, 28.47+/-2.87, 38.08+/
      2.72, 33.47+/-2.41, 31.7+/-2.38, 44.37+/-2.73, respectively) (p<0.01). The
      results of Western blot showed that IL-17 obviously enhanced the phosphorylation
      of P38 induced by TNF-alpha. Compared with the control group, the expression
      level of IL-8 declined significantly (9.47+/-1.36 vs 3.06+/-0.67) when HT-29 was
      cultured together with IL-17 and TNF-alpha (p<0.01). P38 inhibition assay showed
      that P38 pathway played an essential role in IL-17 induced inflammatory response.
      The level of P38 phosphorylation could not be changed after treatment with IL-17
      and TNF-alpha in Act1 stable knockdown HT-29 cell line. CONCLUSION: IL-17
      significantly promoted the gene expression level of TNF-alpha-induced neutrophil
      chemokines and Th17 cells chemokine. IL-17 and TNF-alpha have an obvious
      synergistic effect on P38.

PMID- 25778307
TI  - KRAS discordance between primary and metastatic tumor in patients with metastatic
      colorectal carcinoma.
AB  - PURPOSE: Adding targeted therapies to chemotherapy in metastatic colorectal
      cancer (CRC) improves response rates and survival. KRAS is a predictive indicator
      for anti-epidermal growth factor receptor (EGFR) treatments. The most important
      reasons for KRAS discordance are intratumoral heterogeneity and incorrect
      mutation analysis. Evaluating the status of KRAS in primary and metastatic
      lesions becomes even more crucial to ensure efficient usage of anti-EGFR
      treatments. METHODS: Patients with metastatic CRC, whose primary disease and
      liver and/or lung metastases were operated, were retrospectively evaluated, and
      KRAS assessment was performed on 31 patients who were suitable for DNA analysis.
      Pyrosequencing with polymerase chain reaction (PCR) was used for KRAS analysis.
      RESULTS: The median age of 31 patients diagnosed with rectal cancer (N=13) and
      colon cancer (N=18) was 63 years (range 33-73). Metastasectomy locations included
      the liver (N=27), lung (N=3), and both lung and liver (N=1). KRAS discordance was
      detected in 22% (7/31) of the patients. While 3 patients with detected
      discordance had mutated KRAS in the primary material, wild type KRAS was detected
      in their liver or lung lesions. On the other hand, while 4 patients had wild type
      KRAS in the primary material, mutated KRAS was determined in their liver or lung
      lesions. The McNemar test revealed no significant discordance between primary and
      metastatic disease (p=1.00). No progression free survival (PFS) difference was
      detected between patients with determined discordance and patients with
      undetermined discordance (10.6 vs 14.7 months, p=0.719). CONCLUSION: This is the
      first study to evaluate KRAS discordance between primary and metastasis in CRC
      patients, who underwent metastasectomy, together with survival data. In the
      literature and recent studies with large patient numbers in which modern KRAS
      tests were used, the KRAS discordance rate varies between 3-12%. In our study, a
      higher KRAS discordance (22%) was detected, and no survival difference was
      determined between patients with or without discordance. In recent years, the
      rising interest in borderline resectable disease may bring forward discussions
      related to which material the KRAS status should be analyzed.

PMID- 25778308
TI  - EGFR mutations in patients with non small-cell lung cancer in Bulgaria and
      treatment with gefitinib.
AB  - PURPOSE: To evaluate the EGFR mutations in non small cell lung cancer (NSCLC)
      patients in Bulgaria, as well as to summarize the outcomes of patients with EGFR
      mutations, treated with gefitinib as first- or subsequent-line therapy. METHODS:
      From January 2010 to March 2012 tumor samples from773 NSCLC patients were
      evaluated for EGFR mutations. RESULTS: Seventy-one mutations were found and 34
      patients were treated with gefitinib. Complete remission (CR) was achieved in 2
      patients (6.9%), partial remission (PR) in 11 (37.9%), stable disease (SD) in 13
      (44.8%), and disease progression (PD) in 3 (10.3%). Higher objective response
      rate was seen in women and in never-smokers.The mean progression-free survival
      (PFS) was 11.1 months (95% CI 9.1-13.1), registered in 29 patients (median PFS 10
      months ; 95% CI 8.9-11.1).Tolerability to gefitinib was acceptable, with
      prevalence of skin toxicity, and it did not lead to any significant decline of
      the patients' quality of life. CONCLUSION: This is the first study in Bulgaria to
      evaluate EGFR mutations in NSCLC patients,which were encountered in 9.4% of the
      studied population. The present study confirms the benefits of first- and
      subsequent-lines of gefitinib for the treatment of this patient group. Our data
      give grounds for the conclusion that gefitinib is an effective and well-tolerated
      therapeutic option for patients with locally advanced and metastatic NSCLC
      harboring EGFR mutations.

PMID- 25778309
TI  - Detection of epidermal growth factor receptor mutation in non-small-cell lung
      carcinoma using cytological and histological specimens.
AB  - PURPOSE: Epidermal growth factor receptor (EGFR) mutations are prerequisites for
      the targeted therapy with anti-EGFR tyrosine kinase inhibitors (TKIs) in non
      small-cell lung carcinomas (NSCLCs). In patients with advanced-stage NSCLC,
      sometimes cytological specimens, including those from fine-needle aspiration
      cytology (FNAC) and pleural effusion, are the only materials for mutation
      analysis. The purpose of this study was to compare the results of EGFR mutation
      detection from cytological specimens and histological samples and to evaluate the
      difference between them, therefore to assess if cell block is a valid source for
      detection of EGFR mutation. METHODS: Forty-seven samples from advanced-stage
      NSCLCs were obtained with individually matched cell blocks (CBs) from FNAC (29
      cases) or pleural fluid (18 cases), and formalin-fixed paraffin-embedded (FFPE)
      blocks from biopsy (34 cases) or surgical excision (13 cases). CBs and FFPE
      blocks were simultaneously tested for EGFR hot mutations in exons 18, 19, 20 and
      21 by polymerase chain reaction (PCR)-direct sequencing and amplification
      refractory mutation system (ARMS)-PCR. RESULTS: EGFR mutations were identified in
      18/47 (38.3%) or 21/47 (44.7%) cases using CBs and 16/47 (34.0%) or 19/47 (40.4%)
      using FPPE blocks by PCR-direct sequencing or ARMS-PCR, respectively. The
      incidence of EGFR mutation was not statistically significant between CBs and FFPE
      blocks using PCR-direct sequencing or ARMS-PCR (p=0.668 or p=0.677,
      respectively). CONCLUSION: Our study suggests that cytological specimens are
      optimal for advanced NSCLC. The successful use of these non-invasive specimens in
      molecular pathology is beneficial for patients requiring targeted therapy.

PMID- 25778310
TI  - Accelerated hypofractionated thoracic radiotherapy in limited disease small cell
      lung cancer : comparison with the results of conventionally fractionated
      radiotherapy.
AB  - PURPOSE: To compare accelerated hypofractionated (A-HYPO) radiotherapy (RT) with
      conventionally fractionated (CF) thoracic RT in patients with limited-disease
      small-cell lung cancer (LD-SCLC). METHODS: Out of 217 consecutive LD-SCLC
      patients, treated between 1997 and 2012, 82 received CF-RT (44-60 Gy, 2 Gy/
      fraction) sequentially to 4-6 cycles of platinum-based chemotherapy (CHT), and
      100 received A-HYPO-RT (42 Gy, 2.8 Gy/ fraction). Forty-two patients (42%)
      received "early" (before the 3rd cycle of CHT) A-HYPO-RT, and 58 (58%) patients
      received "late" A-HYPO-RT. Overall survival (OS), locoregional failure risk
      (LRFR) and toxicities were retrospectively evaluated and compared between CF-RT
      and A-HYPO-RT groups (also separately for "early" and "late" A-HYPO-RT). RESULTS:
      Median survival times (MST) for CF-RT and A-HYPO-RT were 18 and 24 months,
      respectively; 3-year OS were 19.1 and 39.4%, respectively (p=0.004). Three-year
      LRFR in CF-RT was 47.3% and 34.0% in the A-HYPO- RT group (p=0.12). Statistically
      significant difference in OS (p=0.007) and LRFR (p=0.03) was observed, favoring
      "early" A-HYPO-RT (MST=27 months, 3-year OS=40.0%, 3-year LRFR=28.4%) over CF-RT.
      Use of CF-RT (relative risk/RR=1.65, p=0.02) and poor CHT compliance (RR=1.69,
      p=0.03) were independent prognostic factors for poor OS; "early" start of RT was
      a favorable although non-significant prognostic factor for LRFR (RR=0.42,
      p=0.05). No difference in toxicities was observed between the groups.
      CONCLUSIONS: A-HYPO-RT results in better outcomes than CF-RT. "Early" A-HYPO-RT
      provides additional benefit in locoregional control and survival, without
      increased toxicity. These results indicate the need for a randomized study on the
      efficacy of A-HYPO-RT.

PMID- 25778311
TI  - Stereotactic body radiotherapy for colorectal lung oligometastases: preliminary
      single-institution results.
AB  - PURPOSE: To present the preliminary results of stereotactic body radiotherapy
      (SBRT) for lung oligometastases originated from colorectal cancer (CRC). METHODS:
      Thirteen patients (9 male, 4 female) with lung oligometastases from CRC were
      prospectively selected for SBRT between July 2009 and July 2013. We used a dose
      risk-adapted schedule of radiation. RESULTS: The median follow-up was 9.16 months
      (range 2-45.6). The median age was 69 years (range 40-84). Three cases (23.1%)
      were treated with 12.5 Gy in 4 fractions (112.5 biological effective dose/BED).
      Four cases (30.8%) received 18Gy (151.2 BED), 2 (15.4%) 7.5 Gy in 8 fractions
      (BED 105) and 4 (30.8%) a monofraction of 34 Gy (149.6 BED). There were 5 (38.5%)
      complete responses, 5 (38.5%) partial responses and 3 (23%) patients remained
      with stable disease. During follow-up 6 patients (46.2%) showed distant
      metastases: liver (N=3, 50%), bone (N=1, 16.6%) and contralateral lung (N=2,
      33.3%). Median time to systemic progression was 9 months. One- and two-year
      distant progression-free survival (DPFS) was 45.8% and 22.9%, respectively. Local
      control (LC), overall survival (OS), and cause-specific survival (CSS) at one-
      and two-years were all 92.3%. A tendency for a better local response and DFPS in
      patients aged <=70 years and BED > 120 Gy was observed. No grade 3-4 toxicity was
      noticed. CONCLUSIONS: Excellent LC and longer DFS could be achieved with SBRT in
      oligometastatic lung disease from CRC, delaying thus disease progression and the
      need for further treatment.

PMID- 25778312
TI  - Correlation of tumor size as independent factor and disease stage with local
      recurrence of non-small cell lung carcinoma and its operability.
AB  - PURPOSE: To analyze the correlation of non-small cell lung carcinoma (NSCLC)
      primary tumor size, independently, and the initial disease stage with the
      incidence of local recurrence (LR) and disease-free survival (DFS), as well as
      the LR operability. METHODS: The research was conducted on 114 patients operated
      due to NSCLC at the Institute for Lung Diseases of the Clinical Center of Serbia
      and the Institute for Oncology and Radiology of Serbia from January 2002 to
      December 2010, who developed LR during the 5-year follow-up. Diagnostic methods
      and surgical approaches were standard, defined by protocols. Standard statistical
      methods and tests were used for data analysis. RESULTS: Statistical analysis
      showed significant difference in DFS and LR incidence in first 2 postoperative
      years related to primary tumor size and stage. Patients with T1 tumors (vs T2 vs
      T3), as well as in earlier disease stage, had significantly longer DFS. LR in the
      first and second year after primary tumor operation occurred more frequently with
      larger primary tumors. Significant correlation was registered between LR
      operability and primary tumor size, as well as LR operability and primary tumor
      stage. CONCLUSIONS: This research highlights size of the primary tumor as
      independent prognostic factor for patients with NSCLC. The likelihood of LR
      increases with larger primary tumor and higher primary tumor stages, while DFS
      decreases. Because larger tumors are more frequently understaged, with occult
      mediastinal metastases, their LR is not possible to be surgically treated.

PMID- 25778313
TI  - miR-150 is a factor of survival in prostate cancer patients.
AB  - PURPOSE: Prostate cancer (PC) is the most common malignant disease in males and
      the second leading cause of cancer related deaths in men in developed countries.
      The purpose of this study was to investigate whether microRNA (miR)-150 is a
      factor influencing survival in prostate cancer patients. METHODS: miR-150 mRNA
      and protein expression levels in prostatic cancer cell lines and healthy tissues
      were determined by quantitative (q) RT-PCR and Western blotting. Additionally,
      the protein expression of miR-150 was detected by immunohistochemistry. RESULTS:
      High miR-150 expression was positively correlated with tumor recurrence or
      metastasis (p=0.010). In addition, PC patients with high miR-150 expression had
      significantly poorer overall survival/OR (hazard ratio/HR, 1.87; 95% confidence
      interval/CI, 1.19-2.94; p=0.006) and poorer disease-free survival/DFS (HR, 1.90;
      95% CI, 1.21- 2.98; p=0.005) than those with low miR-150 expression. The
      cumulative 5-year OS was only 35.19% (95% CI, 26.18- 44.20) in the high miR-150
      expression group, whereas it was 55.93% (95% CI, 43.26-68.60) in the low miR-150
      expression group (p<0.05). Multivariate Cox regression analysis demonstrated that
      the expression of miR-150, tumor size, and number of tumor lesions were
      independent prognostic predictors for OS in PC patients. CONCLUSION: miR-150 was
      overexpressed in PC at both the mRNA and protein levels, and high expression of
      miR-150 could serve as a novel and reliable prognostic biomarker for PC patients.

PMID- 25778314
TI  - Changes in the gene expression profile of the bladder cancer cell lines after
      treatment with Helix lucorum and Rapana venosa hemocyanin.
AB  - PURPOSE: The purpose of this study was to elucidate the mechanism of action of
      the Helix lucorum hemocyanin (HlH), b-HlH-h, and RvH2-g hemocyanins as potential
      agents against bladder cancer. METHODS: We evaluated the viability of 647-V, T
      24, and CAL-29 bladder cancer cell lines after treatment with the tested
      hemocyanins. The cell viability was measured at 72 hrs with MTT and WST-1 assays.
      Acridine orange/propidium iodide double staining was used to discriminate between
      apoptotic and necrotic cells. Gene expression profiling of the 168 genes from
      human inflammatory cytokines and signal transduction pathways were performed on
      the tumor cells before and after hemocyanins' treatment. RESULTS: The results
      showed decreased survival of cancer cells in the presence of HlH and two
      functional units: b-HlH-h and RvH2-g. Acridine orange/propidium iodide double
      staining revealed that the decreased viability was due to apoptosis. The gene
      expression data showed upregulation of genes involved in the apoptosis as well as
      of the immune system activation, and downregulation of the CCL2, CCL17, CCL21,
      CXCL1, and ABCF1 genes. CONCLUSIONS: The present study is the first to report
      gene expression in human cells under the influence of hemocyanins. The mechanism
      of antitumor activity of the HlH, b-HlH-h, and RvH2-g hemocyanins includes
      induction of apoptosis. In addition to the antiproliferative effect,
      downregulation of the genes with metastatic potential was observed. Together with
      the already known immunogenic effect, these findings support further studies on
      hemocyanins as potential therapeutic agents against bladder cancer.

PMID- 25778315
TI  - Expression and significance of FOXP1, HIF-1a and VEGF in renal clear cell
      carcinoma.
AB  - PURPOSE: To investigate the expressions of FOXP1, hypoxia inducible factor (HIF)
      1a and vascular endothelial growth factor (VEGF) in renal cell carcinoma of the
      clear type (CCRCC) and their relationship with the patient clinicopathological
      features. METHODS: The expressions of forkhead box-P1 (FOXP1), HIF-1a and VEGF in
      55 cases of CCRCC tissues were determined using immunohistochemistry. Then, their
      correlations with clinical stage, histological grade and lymph node metastasis
      were analyzed using chi-square test. RESULTS: Thirty-seven of the 55 cases
      (67.3%) of CCRCC expressed FOXP1 with an abnormal expression rate of 38.2%
      (21/55), in which there were 10 cases with positive FOXP1 both in the nucleus and
      the cytoplasm and 11 cases with positive FOXP1 in cell membrane. The abnormal
      expression rate of FOXP1 inhigh grade CCRCC (G3/G4) was significantly higher than
      that in low grade CCRCC (G1/G2, p<0.05). FOXP1 expression was significantly
      correlated with the expression of HIF1 and VEGF (r=0.54, p<0.01 and r=0.37,
      p<0.05, respectively), but was not obviously correlated with clinical stage,
      lymph node metastasis and 5-year overall patient survival (p>0.05). CONCLUSION:
      Abnormal expression of FOXP1 and its deficiency are common events in CCRCC.
      Abnormal expression of FOXP1 may create progression of tumor from low grade to
      high grade by regulating the HIF-1-VEGF pathway.

PMID- 25778316
TI  - The first implementation of IMRT technique for head & neck and prostate cancer
      patients in public sector in Greece: feasibility, treatment planning and dose
      delivery verification using the delta(4PT) Pre-Treatment volumetric quality
      assurance system.
AB  - PURPOSE: Intensity Modulated Radiation Therapy (IMRT) is nowadays the treatment
      of choice, in terms of technique, for either head & neck or prostate cancer. With
      this paper, we are sharing our experience for the first inplementation of IMRT
      planning in the public sector in Greece, and especially in the Aretaieion
      University Hospital of Athens. METHODS: From May 2013 until January 2014 four
      prostate and four head & neck cancer patients were evaluated in the present
      study. We used the ONCENTRA IMRT treatment planning with a step and shoot
      technique in a SIEMENS ONCORE Linac. The dose verification method used was based
      on the delta4(PT) Pre-Treatment volumetric quality assurance system, by Scadidos.
      RESULTS: In all cases, the Relative Standard Deviation between the prescribed and
      the calculated average dose received by the target volume was less than 5%, while
      the gamma-index was more than 90%. The acute toxicity was low and equivalent to
      published data with IMRT technique. CONCLUSION: In conclusion, the first
      implementation of IMRT technique in the Medical School of Athens was feasible and
      safe as well as in terms of dose verification. The IMRT technique is already in
      clinical use and further results with long term radiation induced toxicity will
      be reported.

PMID- 25778317
TI  - Assessment of radiotherapy combined with adjuvant chemotherapy in the treatment
      of patients with advanced nasopharyngeal carcinoma: a prospective study.
AB  - PURPOSE: To explore the clinical efficacy of radiotherapy combined with
      concurrent combination chemotherapy in the treatment of patients with advanced
      nasopharyngeal carcinoma (NPC). METHODS: Two hundred patients with stage III/IV
      NPC were randomly allocated into the treatment group (N=100) and the control
      group (N=100). Patients in the control group received conventional fractionated
      radiotherapy, while patients in the treatment group received conventional
      fractionated radiotherapy combined with concurrent combination chemotherapy with
      cisplatin and 5-fluorouracil (5-FU). Short-term efficacy, radiotherapy toxicity,
      shortand long-term survival were compared. RESULTS: The short-term response rate
      of the treatment group was 96%, which was significantly higher than that of the
      control group (87%, p<0.05). The local radiation toxicity of the treatment group
      was similar to that of the control group p>0.05), but the hematological and
      gastrointestinal toxicities were significantly higher in the treatment group
      p<0.05). The 1-, 3- and 5-year overall survival rates were 87, 80, and 76%,
      respectively, in the treatment group and 74, 64, and 51%, respectively, in the
      control group, significantly favoring the treatment group p<0.05). CONCLUSION:
      Radiotherapy with concurrent combination chemotherapy can improve the prognosis
      of patients with advanced NPC but at the cost of significant toxicity.

PMID- 25778318
TI  - Expression patterns of claudins 1, 4, and 7 and their prognostic significance in
      nasopharyngeal carcinoma.
AB  - PURPOSE: Tight junction (TJ) proteins in the cells organize paracellular
      permeability, and they have a critical role in apical cell-to-cell adhesion and
      epithelial polarity. In our study, the expression patterns of claudins 1, 4, and
      7 and their relationship with prognosis were determined in patients with
      nasopharyngeal carcinoma. METHODS: Claudins 1, 4, and 7 were stained
      immunohistochemically in 18 biopsy samples of nasopharyngeal carcinomas that
      included non-neoplastic surface epithelium and dysplastic epithelium in addition
      to the tumor tissue. The files of these patients were scanned and the stage of
      disease and treatment received were obtained along with demographic data such as
      age and gender. RESULTS: Overexpression of claudins 1, 4, and 7 in non-neoplastic
      surface epithelium was found in 14 (77.7%), 16 (88.8%), and 10 (55.5%) cases
      respectively; in dysplastic surface epithelium overexpression was found in 8
      (44.4%), 13 (72.2%), and 4 (22.2%) cases, respectively; and in invasive tumor
      areas overexpression was found in 13 (72.2%), 9 (50%), and 10 (55.6%) cases
      respectively. Increased claudin 4 expression was related to advanced stage
      (p=0.014). There was a significant relationship determined between claudin 4 and
      7 expression and decreased survival (p=0.018, p=0.024, respectively). CONCLUSION:
      The fact that a statistically significant relationship was found between claudin
      4 expression and advanced stage, and similarly a statistically significant
      relationship was found between claudin 4 & 7 expression and decreased survival
      gives rise to thoughts that especially claudin 4 and 7 could have different
      tumorigenic effects on nasopharyngeal carcinoma besides their known adhesion
      characteristics.

PMID- 25778319
TI  - Sorafenib inhibits liver cancer growth by decreasing mTOR, AKT, and PI3K
      expression.
AB  - PURPOSE: The purpose of this study was to determine the impact of sorafenib on
      PI3K/AKT/mTOR signaling pathway and to further define its mechanism for treating
      hepatocellular carcinoma (HCC). METHODS: Human SMMC-7721 hepatic carcinoma cells
      were treated with or without 4 MUmoL/L sorafenib. SMMC- 7721 cells were harvested
      at various time points (0-48 hrs) and assessed for changes in PI3K, mTOR, and AKT
      protein and mRNA levels. RESULTS: Human SMMC-7721 hepatic tumor cells exposed to
      sorafenib had decreased expression of PI3K/mTOR/AKT. CONCLUSION: Sorafenib
      appears to inhibit hepatic tumor growth by downregulating PI3k/Akt/mTOR signaling
      pathway.

PMID- 25778320
TI  - Is radiofrequency ablation equal to surgical re-resection for recurrent
      hepatocellular carcinoma meeting the Milan criteria? A meta-analysis.
AB  - PURPOSE: To evaluate the clinical efficacy and safety of radiofrequency ablation
      (RFA) with surgical re-resection (SRR) in patients with postoperative recurrent
      hepatocellular carcinoma (RHCC) meeting the Milan criteria. METHODS: A literature
      search was performed to identify comparative studies addressing outcomes of both
      RFA and SRR for RHCC meeting the Milan criteria. Pooled odds ratios (OR) with 95%
      confidence intervals (95% CI) were calculated using either the fixed effects
      model or the random effects model. RESULTS: Five nonrandomized controlled trials
      were included in the analysis. These studies included a total of 543 patients:
      243 treated with RFA and 300 treated with SRR. The SRR group had a better 3-year
      recurrence-free survival rate compared with RFA group (OR 0.44, 95%CI 0.25-0.77,
      p=0.004). However, there were no obvious differences between RFA and SRR group in
      overall survival (OS) rates, re-recurrence rate and OS rates with tumors <= 3cm.
      What's more, the RFA group had a safety advantage with less complications of
      Clavien classification grade II or higher compared with SRR group (OR 0.21, 95%CI
      0.05-0.94, p=0.04). CONCLUSIONS: RFA seemed to be superior to SRR in the
      treatment of patients with RHCC meeting the Milan criteria on account of clinical
      safety. However, these findings have to be carefully interpreted due to the lower
      level of evidence.

PMID- 25778321
TI  - Mortality from cervical cancer in Serbia in the period 1991-2011.
AB  - PURPOSE: The aim of this study was to analyze trends of death rates for cervical
      cancer (CC) on territory of The Republic of Serbia in the period 1991-2011.
      METHODS: In this descriptive epidemiological study, unpublished data of the
      Statistical Office of the Republic of Serbia were used for the analysis of
      mortality due to CC among women in Serbia, from 1991 to 2011. Three different
      types of rates were calculated: crude, age-specific and age-adjusted rates. The
      age-standardized rates were calculated by the direct method of standardization
      using the World Standard Population as standard. The trends were assessed by
      joinpoint linear regression analysis. An average annual percentage change (AAPC)
      and the corresponding 95% confidence intervals (CI) were computed for trends.
      RESULTS: The average age-standardized CC mortality rate (ASCCMR) was 7.03 per
      100,000. The lowest value of the ASCCMR was at the beginning of the observed
      period (6.05 per 100,000) and the highest was 8.17 per 100,000 in 2008. The age
      adjusted CC mortality rates have been continuously and significantly increasing
      (AAPC=+0.7, 95% CI=0.3- 1.1, p<0.05). In all age groups we found increasing
      trends, except in the age group of 65-74 years. CONCLUSION: Since ASCCMR has been
      steadily increasing during the period observed, reducing these rates is highly
      warranted. To achieve this target, an organized CC screening program is
      essential.

PMID- 25778322
TI  - Vitamin D receptor FokI, BsmI, TaqI, ApaI, and EcoRV polymorphisms and
      susceptibility to melanoma: a meta-analysis.
AB  - PURPOSE: The purpose of this study was to examine whether vitamin D receptor
      (lVDR) polymorphisms are associated with susceptibility to melanoma. METHODS: A
      meta-analysis was carried out to investigate the association between the VDR
      FokI, BsmI, TaqI, ApaI, and EcoRV polymorphisms and susceptibility to melanoma.
      RESULTS: A total of 11 studies were evaluated, which included 4,413 patients and
      4,072 controls (all European). The meta-analysis revealed no association between
      melanoma and the BsmI B allele (odds ratio/OR=0.901, 95% confidence
      interval/CI=0.783-1.036, p=0.144). However, an association was shown between
      melanoma and the Bb+bb genotype (OR=0.868, 95% CI=0.767-0.982, p=0.025). No
      association was noticed between melanoma and FokI polymorphism (OR for the F
      allele=1.016, 95% CI=0.869-1.189, p=0.839). Moreover, melanoma risk was not
      associated with the TaqI, ApaI, and EcoRV polymorphisms (OR for the T
      allele=0.986, 95% CI=0.842-1.156, p=0.864; OR for the A allele=0.949, 95%
      CI=0.842-1.069, p=0.388; OR for the E allele=0.993, 95% CI=0.875-1.126, p=0.911,
      respectively). CONCLUSIONS: This meta-analysis demonstrated that the VDR BsmI
      polymorphism is associated with susceptibility to melanoma in Europeans,
      suggesting that carrying the VDR BsmI B allele may be a protective factor against
      melanoma development.

PMID- 25778324
TI  - Dosimetric comparison of intensity-modulated radiotherapy and three-dimensional
      conformal radiotherapy for cerebral malignant gliomas.
AB  - PURPOSE: To compare the dose distribution characteristics of tumor target area,
      normal tissues and organs at risk in patients with malignant gliomas treated with
      intensity- modulated radiotherapy (IMRT) and three-dimensional conformal
      radiotherapy (3DCRT). METHODS: Plans of IMRT and 3DCRT were designed for each of
      the 96 included patients with malignant gliomas. Tumor dose was 60 Gy, and the
      dose distribution differences between the target area and normal tissues were
      compared using dose-volume histogram (DVH). RESULTS: Gross tumor volume (GTV)
      doses for 95% of the volume in the plans of IMRT and 3DCRT were as follows:
      59.82+/-0.43, 57.68+/-0.62 Gy (p<0.05); clinical target volume (CTV): 58.16+/
      0.48, 54.47+/-0.28 Gy (p<0.05); and planning treatment volume (PTV): 57.38+/
      0.74, 54.21+/-0.48 Gy (p<0.05). The conformal index (CI) values of IMRT and 3DCRT
      plans were 0.92+/-0.15 and 0.73+/-0.12, respectively (p<0.05), whereas the
      homogeneity index (HI) values variability of IMRT and 3DCRT were 0.78+/-0.12 and
      1.13+/-0.09 respectively (p<0.05). For normal brain tissues pituitary and optic
      chiasm, the maximum dose (Dmax) and the mean dose (Dmean) of lens exposure
      differed significantly between thw two plans (p<0.05). CONCLUSION: The target
      dose distribution of IMRT was superior to that of 3DCRT in terms of rationality,
      uniformity and conformal nature. IMRT may be better in protecting normal tissue
      and increasing the tumor radiation dose compared with 3DCRT.

PMID- 25778323
TI  - Clinical history of patients with peritoneal carcinomatosis exluded from
      cytoreductive surgery & HIPEC.
AB  - PURPOSE: The aim of this study was to explore the natural course of peritoneal
      carcinomatosis (PC) in patients who are not fit to undergo cytoreductive (CRS)
      surgery and hyperthermic intraperitoneal chemotherapy (HIPEC). METHODS: Over an 8
      year period (2006-2013) 320 patients were excluded from CRS and HIPEC at our
      center. Exclusion criteria were: (a) age >75 years; (b) ASA score >= 3; (c)
      extraperitoneal disease; (d) massive disease involvement of the small bowel; (e)
      disease involvement of the hepatic pedicle or the pancreas; (f) invasion of
      retroperitoneal space; (g) more than two stenoses of the small bowel. Another 130
      patients underwent CRS and HIPEC. RESULTS: In the HIPEC group (N=130), the mean
      overall survival was 26.2+/-11.7 months, while from the non- HIPEC group (N=320),
      200 patients underwent palliative surgery, with a mean overall survival of 11.7+/
      8.3 months. Only 120 patients received palliative chemotherapy with a mean
      overall survival of 7.2+/-4.3 months. CONCLUSION: Our study suggests that, in
      patients unfit to undergo CRS & HIPEC, an exploratory laparotomy and palliative
      surgery should be performed, offering a survival benefit and improved quality of
      life.

PMID- 25778325
TI  - 67kDa laminin receptor regulates the activation of MAPKs through DUSPs in glioma
      cell line U251.
AB  - PURPOSE: All-trans-retinoic-acid (ATRA), the active derivative of vitamin A, is
      critical in regulating cell cycle as well as inhibiting tumor growth and
      angiogenesis. It has been used in the clinical treatment of leukemia. 67kDa
      laminin receptor (67LR), as one of the receptor of laminin, plays an important
      role in tumor cells invasion, proliferation and metastasis. Current research
      indicates that 67LR is highly expressed in glioma and is associated with tumor
      progression. However, the underlying molecular mechanisms, especially the
      signaling pathways involved, have not been reported yet. Therefore it is of great
      importance to clarify its downstream targets. METHODS: The U251 glioma cell line
      was used in this study. Cell Counting Kit-8 was used in cell proliferation assay.
      Quantitative real-time PCR (qRT-PCR) was used to determine the transcription
      level of dual specificity phosphatases (DUSPs). Western blot analysis was used to
      detect the expression of mitogen activated protein kinases (MAPKs) and
      phosphorylated MAPKs. RESULTS: 67LR could influence the transcription of DUSPs
      and expression of MAPKs. ATRA could enhance the expression of 67LR in U251 cells
      and this enhancement was dose-dependent. ATRA was able to inhibit the growth of
      U251 cells. CONCLUSIONS: ATRA expressed significant therapeutic effect on glioma
      cells, and 67LR is not the only factor that can influence the proliferation of
      U251 cells.

PMID- 25778326
TI  - LEP and LEPR polymorphisms in non-Hodgkin lymphoma risk: a systematic review and
      pooled analysis.
AB  - PURPOSE: The purpose of this systematic meta-analysis was to evaluate the
      association between leptin (LEP) and leptin receptor (LEPR) gene polymorphisms
      and non-Hodgkin lymphoma (NHL) risk. METHODS: All studies published up to July
      2014 on the association between LEP and LEPR polymorphisms and NHL risk were
      identified by searching PubMed, Web of Science, EMBASE, and Google Scholar. Odds
      ratios (ORs) with 95% confidence intervals (CIs) for LEP and LEPR polymorphisms
      and NHL were calculated with fixed-effects and random-effects models. RESULTS:
      LEP G2528A polymorphism was associated with increased, yet not statistically
      significant risk of NHL (homozygote comparison, OR=1.27, 95% CI=1.01-1.60,
      p=0.63; heterozygote comparison, OR=1.13, 95% CI=0.86-1.49, p=0.14; dominant
      model, OR=1.18, 95% CI=0.99-1.41, p=0.21; recessive model, OR=1.18, 95% CI=0.97
      1.43, p=0.78; additive model, OR=1.14, 95% CI=1.01-1.28, p=0.52). Significant
      decrease of NHL risk was found in LEP A19G polymorphism, while no links were
      detected with the LEPR polymorphisms studied. In subgroup analysis, the pooled
      results showed that LEP A19G polymorphism was associated with decreased risk of
      follicular lymphoma (FL) (homozygote comparison, OR=0.56, 95% CI=0.37-0.85,
      p=0.69). However, no evidence of a significant association was observed in
      diffuse large B-cell lymphoma (DLBCL) for variant genotypes of all single
      nucleotide polymorphisms (SNPs). CONCLUSIONS: LEP G2548A polymorphism contributes
      to NHL susceptibility. Also, our results provide evidence that LEP A19G
      polymorphism is associated with decreased risk of NHL, especially in FL. Further
      large-scale and well-designed studies are needed to confirm this association.

PMID- 25778328
TI  - Nurses' practices in targeted therapies in Turkey.
AB  - PURPOSE: The number of targeted agents has increased over the last years. The aim
      of this study was to explore the current practice and knowledge of nurses about
      targeted therapies and to identify the gap in their management in Turkey.
      METHODS: Nurses who attended to the oncology nursing educational programs
      organised by the Turkish Oncology Nursing Association were invited to
      participate. A total of 187 nurses from 29 cities responded. Data were collected
      via a 30-item questionnaire on demographics and knowledge and practices on
      targeted therapies. Following this survey nurses were invited to participate in
      "target" courses. RESULTS: More than half of them (57.2%) stated they were
      willing to receive information on targeted therapies, mostly through in-service
      education (32.7%). Also, most of them were partly (67.3%) or not satisfied
      (24.3%) with their knowledge. Only few explained what targeted therapies are and
      how they work. While most of them responded correctly about how and where to
      store targeted drugs, few (1.8%) wrote that these agents should be stored in
      freezer. The majority stated that targeted agents should be prepared like the
      chemotherapy drugs. CONCLUSIONS: Lack of knowledge may cause errors and influence
      drug effectiveness. Nurses need to be supported with information. This survey
      revealed the needs in nursing practice over targeted therapies, side-effects and
      management.

PMID- 25778327
TI  - Histone deacetylase inhibitors repress chondrosarcoma cell proliferation.
AB  - PURPOSE: Due to the high resistance to conventional therapy, there is still no
      convincingly effective treatment for chondrosarcoma. As a promising new treatment
      strategy, histone deacetylase inhibitors (HDACIs) have been reported to induce
      cell arrest, apoptosis and differentiation in some kinds of malignancies, but how
      HDACi exert their effects on chondrosarcoma is not well understood yet. METHODS:
      We investigated the effects of HDACIs trichostatin A (TSA) and sodium valproate
      (VPA) on chondrosarcoma cells in vitro and in vivo. The cell proliferation and
      cell cycle were examined in two chondrosarcoma cell lines, SW1353 and JJ012, by
      MTS and flow cytometry assays, respectively. The in vivo effects of HDACIs were
      investigated by assessing the chondrosarcoma growth in a mouse xenograft model.
      RESULTS: Our results showed that TSA and VPA significantly repressed the
      proliferation of chondrosarcoma cells in a concentration-dependent manner. Flow
      cytometry indicated that TSA arrested the cell cycle in G2/M phase and VPA
      arrested the cell cycle in G1 phase. The tumor growth was markedly suppressed in
      mice treated with TSA and VPA. CONCLUSIONS: HDACIs significantly repress the
      proliferation of chondrosarcoma cells in vitro and in vivo. Our findings imply
      that HDACIs may provide a novel therapeutic target for the treatment of
      chondrosarcoma.

PMID- 25778329
TI  - Proteomics pattern of peritoneal sApo-2L but not CD200 (OX-2) as a possible
      screening biomarker for metastatic ovarian, endometrial and breast carcinoma.
AB  - PURPOSE: The purpose of this study was to evaluate the soluble Apo-2L (sApo-2L)
      levels in the ascitic fluid and to study its potential in detecting malignant
      ascites and soluble CD200 (sCD200,sOX-2) levels so as to predict its clinical
      usage for detecting stage 4 metastatic endometrial, ovarian and breast cancer in
      serum samples. METHODS: Ascitic fluid from 53 and blood from 25 subjects without
      known malignancy on admission were collected. There were 14 breast cancer (BC),
      17 ovarian cancer (OC) and 19 endometrial cancer (EC) patients diagnosed later
      on. Blood samples for sApo-2L, sCD200, liver function tests and CEA, CA-19.9 and
      CA-125 were always taken and assayed in the morning. RESULTS: Significantly low
      levels of sApo-2L were observed in peritoneal fluid from OC and EC patients
      compared to benign peritoneal fluid from control individuals. Positive
      correlation was observed between sApo-2L and aspartate aminotransferase (AST) in
      benign peritoneal fluid and sCD200, and creatinine and sCD200 and platelets in OC
      patients; also, sCD200 and CEA in EC patients and sCD200 and blood urea nitrogen
      (BUN) in healthy subjects. CONCLUSIONS: Our data indicate that low proteomics
      pattern of sApo-2L but not sCD200 is a good biochemical marker. Further decline
      in the level of sApo-2L was seen in EC compared to OC. Since higher levels of
      sApo-2L were seen with higher levels of AST, the liver might be involved in its
      metabolism. The positive correlation detected between sCD200 and creatinine,
      platelets, CEA and BUN needs to be elucidated.

PMID- 25778330
TI  - Polymorphisms of GSTA1 contribute to elevated cancer risk: evidence from 15
      studies.
AB  - PURPOSE: Glutathione S-transferases (GSTs) are involved in the detoxification of
      carcinogens, and may be linked to carcinogenesis. As a vital component of GSTs,
      GSTA1 plays an important role in carcinogenesis. However, the studies about the
      effect of GSTA1 polymorphisms on cancer risk are limited and the conclusions are
      contradictory. This meta-analysis aimed to evaluate the association between GSTA1
      polymorphisms (-567T>G, (69C>T and -52G>A) and cancer risk. METHODS: A literature
      search of PubMed and Web of Science databases was conducted from their inception
      through December 2013. Crude odds ratios (ORs) with 95% confidence intervals
      (CIs) were calculated to assess the association of GSTA1 polymorphisms and cancer
      risk. RESULTS: A total of 15 studies were enrolled, and the results indicated
      that GSTA1 BB genotype was associated with elevated cancer risk, especially in
      colorectal cancer. Further stratifications showed that GSTA1 BB genotype was
      associated with increased cancer risk in Caucasian populations and in the study
      with population-based controls. CONCLUSIONS: This meta-analysis suggested that
      GSTA1 BB genotype was a risk factor for colorectal cancer, especially in
      Caucasian populations.

PMID- 25778331
TI  - Association between estrogen receptor 1 (ESR1) genetic variations and cancer
      risk: a meta-analysis.
AB  - PURPOSE: Emerging published reports on the association between estrogen receptor
      1 (ESR1) genetic variation and cancer susceptibility are inconsistent. This
      review and meta- analysis was performed to achieve a more precise evaluation of
      this relationship. METHODS: A literature search of PubMed database was conducted
      from the inception of this study through April 1st 2014. Crude odds ratios (ORs)
      with 95% confidence intervals (95% CIs) were calculated to assess the
      association. RESULTS: 87 studies were enrolled in this meta-analysis. The results
      indicated that PvuII (T>C) polymorphism was associated with an increased risk of
      hepatocellular carcinoma (HCC) and prostate cancer, in contrast with the
      decreased risk of gallbladder cancer. No significant association was found in
      Asian and Caucasian populations. Furthermore, XbaI (A>G) genetic variation was
      only associated with an increased risk of prostate cancer, but was not related
      with race. In addition, T594T (G>A) polymorphisms were significantly associated
      with an increased risk of cancer, especially in Asian populations. CONCLUSIONS:
      This meta-analysis indicated that PvuII (T>C) genetic variation may be risk
      factor for HCC, prostate cancer and gallbladder cancer. Meanwhile, XbaI (A>G)
      polymorphism may be potential prognostic factor for prostate cancer. Furthermore,
      T594T (G>A) was closely related with cancer susceptibility, especially in Asian
      populations.

PMID- 25778332
TI  - Association of rs712 polymorphism in Kras gene 3'-luntranslated region and cancer
      risk: a meta-analysis.
AB  - PURPOSE: Mutation and polymorphism of Kras oncogene are considered as candidate
      risk factor and drug response predictor for cancer. However, the conclusions of
      accumulating reports related to the relationship of rs712 of Kras gene and risk
      of cancer remain nuclear. METHODS: We performed a meta-analysis including 6
      eligible studies containing 1661 cases and 2139 controls to explore the role of
      rs712 in the risk of cancer development. RESULTS: Meta-analysis results showed
      that rs712 allele T (P(H)=0.08, odds ratio/OR=1.35, 95% confidence interval/
      CI=1.17-1.55) and genotype TT (P(H)=0.174, OR=2.32, 95% CI=1.60-3.37), and allele
      T carrier genotype (GT/TT) (P(H)=0.14, OR=1.30, 95% CI=1.10-1.55) were strongly
      associated with cancer in Chinese population. No evidence of association was
      observed between rs712 and risk of cancer in overall population. CONCLUSION: The
      findings suggested that allele T, genotype TT and allele T carrier (GT/TT) of
      rs712 may increase susceptibility to cancer risk in Chinese population, and can
      be used as a genetic factor for evaluating risk of cancer.

PMID- 25778333
TI  - The effect of anaesthetic management on neutrophil gelatinase associated
      lipocalin (NGAL) levels after robotic surgical oncology.
AB  - PURPOSE: The main objective of this study was to compare the effect of two
      anaesthetic techniques (general vs combined) on plasma levels of NGAL (Neutrophil
      Gelatinase Associated Lipocalin) after robotic urogenital oncosurgery. The
      secondary objective was to correlate NGAL levels with the incidence of acute
      kidney injury (AKI). METHODS: This was a longitudinal prospective study. Forty
      patients were included and randomized in 2 groups: group C (N=16 cases; combined
      general-epidural anesthesia) and group G (N=24 cases; control group with general
      anesthesia). Demographic data, Charlson Comorbidity Index, Apache II, SOFA and
      ASA scores were similar in both groups. Serum creatinine was determined
      preoperatively and every 24 hrs for 4 postoperative days to identify AKI
      according to RIFLE and AKIN criteria. Serum NGAL was determined at 6 and 12 hrs
      after induction of anesthesia. RESULTS: Serum creatinine increased at 24 hrs
      postoperatively in both groups as compared to baseline, but significant changes
      were registered only in the G group (p(control) = 0.004). Serum NGAL increased
      significantly in both groups as compared with baseline levels (pcase=0.0034 vs
      p(control)=0.0001). The incidence of AKI was 12.50% (95% CI 0.4-34) in the C
      group and 37.50% (95% CI 17-58) in the G group (p=0.0909), respectively.
      CONCLUSION: Impaired renal function and AKI occurred in robot-assisted
      laparoscopic urogenital oncosurgery under both general and combined anaesthesia.
      The incidence of AKI was lower in patients undergoing combined anesthesia
      compared to general anaesthesia after robotic urogenital oncosurgery but the
      difference did not reach statistical significance. However, plasma levels of NGAL
      were significantly increased at 6 and 12 hrs in the general anaesthesia group as
      compared with combined anaesthesia. NGAL may be a better marker in detecting
      postoperative acute kidney injury. Further studies are needed.

PMID- 25778334
TI  - The correlation between a chronic inflammatory marker Tartrate-resistant acid
      phosphatase 5a with cancer cachexia.
AB  - PURPOSE: The mechanism of cancer cachexia remains unclear and inflammatory
      cytokines may play a role in its development. Interleukin-6 (IL-6), C-reactive
      protein (CRP) and tumor necrosis factor-alpha (TNFalpha) are known to be
      associated with cancer cachexia. Tartrate-resistant acid phosphatase 5a (TRACP5a)
      is proposed to be related to chronic inflammation. In this study we hypothesize
      that TRACP5a is a chronic inflammatory marker that is correlated with cancer
      cachexia. METHODS: Fifty-five cancer patients with and without cancer cachexia
      were enrolled from January 2009 to December 2012. Body mass index (BMI) was
      measured and serum total cholesterol, triglycerides and albumin were examined to
      evaluate the nutritional status. IL-6, CRP and TRACP5a protein activity were
      evaluated. RESULTS: Inflammatory markers including IL-6, and CRP were
      significantly elevated in patients with cancer cachexia (p=0.0075 and 0.0021,
      respectively). Patients with cachexia also had higher CRP/albumin ratio
      (p=0.0265). TRACP5a activity, TRACP5a protein and their combinations with albumin
      were increased in the cancer cachexia groups but without significant difference.
      There were good correlations between IL-6, CRP, and BMI. Patients with higher
      TRACP5a activity had shorter survival (p=0.004). CONCLUSION: TRACP5a may be a
      promising chronic inflammatory marker and may play a prognostic role in cancer
      cachexia. Further large-scale prospective studies are warranted to confirm its
      role in the cancer cachexia process.

PMID- 25778335
TI  - A 12-year experience at a tertiary hospital on patients with multiple primary
      malignant neoplasms.
AB  - PURPOSE: The incidence of multiple primary malignant neoplasms (MPMN) has
      dramatically increased. The purpose of this retrospective study was to present
      the 12-year experience at a University Hospital in patients with MPMN and to
      investigate the role of genetic factors in their pathogenesis. METHODS: The
      medical records of 7516 cancer patients, treated in our Institution from 2000 to
      2012, were reviewed. Diagnosis of MPMN was based on the Warren and Gates'
      criteria. RESULTS: Among 7516 patients, 39 (0.5%) (10 men, mean age 70.0+/-6.98
      years, and 29 women, mean age 64.7+/-8.24 years) presented with MPMN. Eighty-two
      percent of them developed 2 primary malignant neoplasms (PMNs), whereas 3 PMNs
      were developed in 7 patients. Breast cancer was the most common cancer type
      diagnosed among female patients (59%); 14 and 3 had 2 and 3 PMNs, respectively.
      Eight had a family history of breast cancer while in 3 genetic testing revealed
      mutations in BRCA1 and BRCA2 genes. The second most common type of malignancy was
      colorectal cancer (24%); 5 developed 2 PMNs, whereas 2 developed 3 PMNs. Five
      patients had a family history of colorectal cancer. Colon cancer was the most
      frequent neoplasm among male patients (50%; 3 developed 2 and 2 3 PMNs. In 2
      patients the family history was positive for colorectal cancer. CONCLUSIONS:
      Although many factors may contribute to MPMN development, positive family history
      and inherent mutations significantly predispose to MPMN appearance. Thus,
      management of MPMN patients should be based on a detailed family history and
      genetic testing.

PMID- 25778336
TI  - Retrospective evaluation of totally implantable venous access port devices: early
      and late complications.
AB  - PURPOSE: The role totally implantable vascular devices (TIVAD) have an important
      role in providing care to cancer patients who require continuous or frequent
      venous access route either for their primary or supportive care treatments. This
      retrospective study aimed to analyze the efficacy of TIVAD and device-related
      complications. METHODS: A total of 324 consecutive patients (185 male,139 female,
      median age 56 years, mean 48 +/- 10.91; min:16, max:87) who were implanted with
      TIVAD between January 2012 - May 2014 were included. We retrospectively assessed
      all TIVAD complications and focused on early and late complications. RESULTS: A
      total of 324 devices were implanted successfully without major complications. The
      overall complication rate was 33.95% )N=110). Of them, 87 (26.85%) were early and
      23 (7.09%) were late complications. In total, 39 (11.23%) catheters were removed,
      in 8 (2.30%) patients due to complication and in 31 (9.56%) due to the end of
      treatment. CONCLUSION: Most of the complications of TIVAD were early without
      requiring removal. Port catheters for chemotherapy are safe and well tolerated
      with acceptable complication rates.

PMID- 25778337
TI  - Proceedings of the 9th International Congress on Peritoneal Surface Malignancies,
      October 9th - 11th 2014, Amsterdam.

PMID- 25778338
TI  - A systemic late recurrence after the first operation in a patient diagnosed with
      early-stage breast cancer: the latest recurrence in the literature.

PMID- 25778339
TI  - Acquired C1 esterase inhibitor deficiency in a marginal zone lymphoma patient
      treated with rituximab.

PMID- 25778340
TI  - Targeted immunotherapies overtaking emerging oncology market value based growth.

PMID- 25778341
TI  - Extracranial recurrence in the bone marrow of adult medulloblastoma patient - a
      therapeutic trap.

PMID- 25778342
TI  - Intra-carotid chemotherapy of mandible osteosarcoma.

PMID- 25778343
TI  - Rene-Theophile-Hyacinthe Laennec (1781-1826) and the description of metastatic
      pulmonary melanoma.
AB  - In 19th century, the anatomo-clinical school of Paris linked clinical signs with
      anatomical lesions establishing clinical medicine. One of the most enlightened
      promoters of this method was the French physician Rene-Theophile-Hyacinthe
      Laennec, known as the inventor of stethoscope. In our article, we reveal his work
      on pulmonary melanoma. 

PMID- 25778344
TI  - Cell Type-Specific Control of Spike Timing by Gamma-Band Oscillatory Inhibition.
AB  - Many lines of theoretical and experimental investigation have suggested that
      gamma oscillations provide a temporal framework for cortical information
      processing, acting to either synchronize neuronal firing, restrict neuron's
      relative spike times, and/or provide a global reference signal to which neurons
      encode input strength. Each theory has been disputed and some believe that gamma
      is an epiphenomenon. We investigated the biophysical plausibility of these
      theories by performing in vitro whole-cell recordings from 6 cortical neuron
      subtypes and examining how gamma-band and slow fluctuations in injected input
      affect precision and phase of spike timing. We find that gamma is at least
      partially able to restrict the spike timing in all subtypes tested, but to
      varying degrees. Gamma exerts more precise control of spike timing in pyramidal
      neurons involved in cortico-cortical versus cortico-subcortical communication and
      in inhibitory neurons that target somatic versus dendritic compartments. We also
      find that relatively few subtypes are capable of phase-based information coding.
      Using simple neuron models and dynamic clamp, we determine which intrinsic
      differences lead to these variations in responsiveness and discuss both the
      flexibility and confounds of gamma-based spike-timing systems. 

PMID- 25778345
TI  - Region-Specific Summation Patterns Inform the Role of Cortical Areas in Selecting
      Motor Plans.
AB  - Given an instruction regarding which effector to move and what location to move
      to, simply adding the effector and spatial signals together will not lead to
      movement selection. For this, a nonlinearity is required. Thresholds, for
      example, can be used to select a particular response and reject others. Here we
      consider another useful nonlinearity, a supralinear multiplicative interaction.
      To help select a motor plan, spatial and effector signals could multiply and
      thereby amplify each other. Such an amplification could constitute one step
      within a distributed network involved in response selection, effectively boosting
      one response while suppressing others. We therefore asked whether effector and
      spatial signals sum supralinearly for planning eye versus arm movements from the
      parietal reach region (PRR), the lateral intraparietal area (LIP), the frontal
      eye field (FEF), and a portion of area 5 (A5) lying just anterior to PRR. Unlike
      LIP neurons, PRR, FEF, and, to a lesser extent, A5 neurons show a supralinear
      interaction. Our results suggest that selecting visually guided eye versus arm
      movements is likely to be mediated by PRR and FEF but not LIP. 

PMID- 25778347
TI  - Food processing and allergenicity.
AB  - Food processing can have many beneficial effects. However, processing may also
      alter the allergenic properties of food proteins. A wide variety of processing
      methods is available and their use depends largely on the food to be processed.
      In this review the impact of processing (heat and non-heat treatment) on the
      allergenic potential of proteins, and on the antigenic (IgG-binding) and
      allergenic (IgE-binding) properties of proteins has been considered. A variety of
      allergenic foods (peanuts, tree nuts, cows' milk, hens' eggs, soy, wheat and
      mustard) have been reviewed. The overall conclusion drawn is that processing does
      not completely abolish the allergenic potential of allergens. Currently, only
      fermentation and hydrolysis may have potential to reduce allergenicity to such an
      extent that symptoms will not be elicited, while other methods might be promising
      but need more data. Literature on the effect of processing on allergenic
      potential and the ability to induce sensitisation is scarce. This is an important
      issue since processing may impact on the ability of proteins to cause the
      acquisition of allergic sensitisation, and the subject should be a focus of
      future research. Also, there remains a need to develop robust and integrated
      methods for the risk assessment of food allergenicity. 

PMID- 25778346
TI  - Causal Interactions Within a Frontal-Cingulate-Parietal Network During Cognitive
      Control: Convergent Evidence from a Multisite-Multitask Investigation.
AB  - Cognitive control plays an important role in goal-directed behavior, but dynamic
      brain mechanisms underlying it are poorly understood. Here, using multisite fMRI
      data from over 100 participants, we investigate causal interactions in three
      cognitive control tasks within a core Frontal-Cingulate-Parietal network. We
      found significant causal influences from anterior insula (AI) to dorsal anterior
      cingulate cortex (dACC) in all three tasks. The AI exhibited greater net causal
      outflow than any other node in the network. Importantly, a similar pattern of
      causal interactions was uncovered by two different computational methods for
      causal analysis. Furthermore, the strength of causal interaction from AI to dACC
      was greater on high, compared with low, cognitive control trials and was
      significantly correlated with individual differences in cognitive control
      abilities. These results emphasize the importance of the AI in cognitive control
      and highlight its role as a causal hub in the Frontal-Cingulate-Parietal network.
      Our results further suggest that causal signaling between the AI and dACC plays a
      fundamental role in implementing cognitive control and are consistent with a two
      stage cognitive control model in which the AI first detects events requiring
      greater access to cognitive control resources and then signals the dACC to
      execute load-specific cognitive control processes. 

PMID- 25778348
TI  - Protective properties of Salvia lavandulifolia Vahl. essential oil against
      oxidative stress-induced neuronal injury.
AB  - Salvia lavandulifolia Vahl., known as "Spanish sage", has potential value in
      dementia for its sedative, antioxidant, anti-inflammatory and anticholinesterase
      properties. This work aimed to evaluate the in vitro neuroprotective activity of
      S. lavandulifolia essential oils, obtained from plants at different phenological
      stages (vegetative and flowering phases) and plants grown at different densities,
      against H2O2-induced oxidative stress in PC12 cells. The effect on cell viability
      and morphology, lipid peroxidation, GSH/GSSG ratio, intracellular ROS levels,
      antioxidant enzymes (CAT, SOD, GR, GPx, HO-1) and apoptotic enzymes was
      investigated. Comparing with H2O2-treated PC12 cells, pretreatments with
      essential oil samples attenuated morphological changes and loss of cell
      viability, decreased MDA levels and intracellular ROS production and increased
      GSH/GSSG ratio. Moreover, Spanish sage increased antioxidant status as evidenced
      in an increase of antioxidant enzyme activity and protein expression and
      inhibited caspase-3 activity. Furthermore, our results suggest that S.
      lavandulifolia essential oils are able to activate Nrf2 transcription factor.
      Collectively, the sample of essential oil obtained with the highest densities of
      planting and at flowering phase exerted the major neuroprotective activity. Our
      findings demonstrate that S. lavandulifolia essential oils may have therapeutic
      value for the prevention and treatment of neurodegenerative diseases associated
      with oxidative stress-induced neuronal injury. 

PMID- 25778349
TI  - Assessment of potential toxicological aspects of dietary exposure to silicon-rich
      spirulina in rats.
AB  - Silicon has beneficial effects especially on bones and skin and is important in
      cardiovascular pathophysiology. Furthermore, in spontaneously hypertensive rats,
      it reduces hypertension and increases antihypertensive and antiatherogenic gene
      expressions in the aorta. Thus, incorporating silicon into spirulina could be a
      way to produce a bioavailable food supplement. The potential toxic effects of
      silicon-rich spirulina (SES) through haematological and biochemical parameters
      and inflammatory and oxidative status were evaluated in rats' blood and liver
      tissue. The study consisted in a 90-day experiment on female and male rats
      supplemented with three doses (28.5, 57 and 285 mg/kg BW/day) of SES. No
      mortality, abnormal clinical signs, behavioural changes or macroscopic findings
      were observed whatever the groups. Haematological parameters were not modified in
      SES treated-groups. No marked change was recorded in biochemical parameters The
      liver endogenous antioxidant enzymes (SOD, GPx, catalase) activities were not
      modified whatever the gender and the dose, just as markers of oxidative stress
      (O2 degrees (-), TBARS, thiols) and inflammation such as IL-6 and TNF-alpha. Our
      findings indicate that dietary supplementation of silicon-rich spirulina on rats
      has no harmful side nor toxic effects and could be beneficial especially in the
      case of suspicion or installation of pathologies due to oxidative stress. 

PMID- 25778350
TI  - Dynamic nanomechanical properties of novel Si-rich intermetallic coatings growth
      on a medical 316 LVM steel by hot dipping in a hypereutectic Al-25Si alloy.
AB  - This aim of this study is to determine the elastoplastic properties of Ni-free
      Al3FeSi2 intermetallic coatings grown on medical stainless steel under different
      experimental conditions. Elastoplastic properties are defined by the plasticity
      index (PI), which correlates the hardness and the Young's modulus. Special
      emphasis is devoted to correlate the PI with the wear resistance under sliding
      contact, determined by scratch testing, and fracture toughness, determined by
      using a novel method based on successive impacts with small loads. With regard to
      the substrate, the developed coatings are harder and exhibit a lower Young's
      reduced modulus, irrespective of the experimental conditions. It has been shown
      that preheating of the samples prior to hot dipping and immersion influences the
      type and volume fraction of precipitates, which in turn also affect the
      nanomechanical properties. The higher the preheating temperature is, the greater
      the Young's reduced modulus is. For a given preheating condition, an increase of
      the immersion time yields a decrease in hardness. Although apparent friction
      coefficients of coated specimens are smaller than those obtained on AISI 316 LVM,
      they increase when using preheating or higher immersion times during processing,
      which correlates with the PI. The presence of precipitates produces an increase
      in fracture toughness, with values greater than those presented by samples
      processed on melted AlSi alloys with lower Si content (12 wt%). Therefore, these
      intermetallic coatings could be considered "hard but tough", suitable to enhance
      the wear resistance, especially when using short periods of immersion.

PMID- 25778351
TI  - Fabrication, pore structure and compressive behavior of anisotropic porous
      titanium for human trabecular bone implant applications.
AB  - Porous titanium with average pore size of 100-650 MUm and porosity of 30-70% was
      fabricated by diffusion bonding of titanium meshes. Pore structure was
      characterized by Micro-CT scan and SEM. Compressive behavior of porous titanium
      in the out-of-plane direction was studied. The effect of porosity and pore size
      on the compressive properties was also discussed based on the deformation mode.
      The results reveal that the fabrication process can control the porosity
      precisely. The average pore size of porous titanium can be tailored by adjusting
      the pore size of titanium meshes. The fabricated porous titanium possesses an
      anisotropic structure with square pores in the in-plane direction and elongated
      pores in the out-of-plane direction. The compressive Young's modulus and yield
      stress are in the range of 1-7.5 GPa and 10-110 MPa, respectively. The dominant
      compressive deformation mode is buckling of mesh wires, but some uncoordinated
      buckling is present in porous titanium with lower porosity. Relationship between
      compressive properties and porosity conforms well to the Gibson-Ashby model. The
      effect of pore size on compressive properties is fundamentally ascribed to the
      aspect ratio of titanium meshes. Porous titanium with 60-70% porosity has
      potential for trabecular bone implant applications.

PMID- 25778382
TI  - I think therefore I am: Rest-related prefrontal cortex neural activity is
      involved in generating the sense of self.
AB  - The sense of self has always been a major focus in the psychophysical debate. It
      has been argued that this complex ongoing internal sense cannot be explained by
      any physical measure and therefore substantiates a mind-body differentiation.
      Recently, however, neuro-imaging studies have associated self-referential
      spontaneous thought, a core-element of the ongoing sense of self, with
      synchronous neural activations during rest in the medial prefrontal cortex (PFC),
      as well as the medial and lateral parietal cortices. By applying deep
      transcranial magnetic stimulation (TMS) over human PFC before rest, we disrupted
      activity in this neural circuitry thereby inducing reports of lowered self
      awareness and strong feelings of dissociation. This effect was not found with
      standard or sham TMS, or when stimulation was followed by a task instead of rest.
      These findings demonstrate for the first time a critical, causal role of intact
      rest-related PFC activity patterns in enabling integrated, enduring, self
      referential mental processing. 

PMID- 25778383
TI  - Reversible cerebral vasoconstriction in Guillain-Barre syndrome.
AB  - We present a 51-year-old woman with clinical and neurophysiological evidence of
      Guillain-Barre syndrome (GBS) who developed a generalised headache and autonomic
      dysfunction with sinus tachycardia, hypertension, gastrointestinal motility
      symptoms and urinary retention. MRI/MRA demonstrated cerebral vasoconstriction
      and a small convexity subarachnoid haemorrhage which resolved after 3 months.
      Reversible cerebral vasoconstriction syndrome (RCVS) is characterised by
      headache, focal neurological deficits or seizures, and reversible cerebral
      vasoconstriction. To our knowledge, this is the first reported case of RCVS
      complicating autonomic dysfunction in GBS. This case depicts a rare complication
      of a common condition and also sheds light on the potential mechanism of RCVS.
      Neurologists should be aware that autonomic dysfunction can lead to RCVS in GBS.

PMID- 25778384
TI  - Minocycline-induced polyarteritis nodosa-like vasculitis presenting as brainstem
      stroke.
AB  - Minocycline use has been associated with the development of autoimmune disorders,
      including drug-induced vasculitis. Previously published reports suggest that
      clinical manifestations are limited to cutaneous, constitutional, or
      musculoskeletal symptoms. To our knowledge there has been only one reported
      patient with ischemic stroke in the setting of minocycline-induced vasculitis. We
      describe a 26-year-old woman, with no vascular risk factors, who had an ischemic
      pontine stroke in the setting of biopsy-proven minocycline-induced polyarteritis
      nodosa-like vasculitis. Discontinuation of minocycline resulted in resolution of
      the vasculitis, and she has not had any recurrent ischemic events. This report
      shows that ischemic strokes may occur as a result of minocycline-induced
      vasculitis. While this is likely a rare association, recognition is important
      given the widespread use of minocycline and the potential for devastating
      consequences in a young population. Consequently, drug-induced vasculitis should
      be considered in patients with an ischemic stroke taking minocycline. 

PMID- 25778385
TI  - Spontaneous intracranial hypotension resulting from a thoracic osteophyte.
AB  - We report a 34-year-old woman who presented with progressive postural headache
      and neck tightness over 1week. We confirmed the diagnosis of spontaneous
      intracranial hypotension (SIH) and spinal images showed a thoracic osteophyte
      caused the cerebrospinal fluid (CSF) leak. SIH caused by spinal CSF leak is
      generally thought to be a consequence of deficiency of the spinal meninges in
      conjunction with trivial trauma. Less commonly, spinal bony pathology can lead to
      SIH. We reviewed 13 reported patients with bony structural pathology related SIH.
      After two to three epidural blood patches, eight patients underwent surgery. They
      generally had good outcomes. In conclusion, even though surgical repair confers
      specific risks, it should be considered after repetitive failures of epidural
      blood patches. The long-term prognoses of surgical versus non-surgical patients
      warrants further investigation. 

PMID- 25778386
TI  - Intradural, extramedullary amyloidoma involving cervical and thoracic spine.
AB  - We present the case of a 46-year-old woman with insidious lower extremity
      paralysis and bowel and bladder disruption found to have an intradural,
      extramedullary amyloidoma from the levels of C4-T4. To our knowledge, this is the
      first known reported case of amyloidoma occurring in this location. Solitary
      amyloidoma of the spine is a rare entity typically manifesting as an extradural
      tumor with bony involvement. 

PMID- 25778387
TI  - Diagnostic accuracy of abnormal galactographic and sonographic findings in the
      diagnosis of intraductal pathology in patients with abnormal nipple discharge.
AB  - The purpose of the study was to compare the diagnostic accuracy of the
      combination of galactography and ultrasound in patients with pathologic nipple
      discharge. Fifty-six patients with pathologic nipple discharge were included in
      the study. Sensitivity, specificity, and positive (PPV) and negative predictive
      value (NPV) for each method and the combination of both were calculated. Both
      methods together had a sensitivity, specificity, PPV, and NPV of 91%, 17%, 61%,
      and 57%. The combined sensitivity of galactography and ultrasound for intraductal
      pathologies is higher than either modality alone, with a low specificity. No
      specific signs exist to predict benign or malignant lesions. 

PMID- 25778388
TI  - Dynamic contrast-enhanced magnetic resonance imaging in Head and Neck Cancer:
      differentiation of new H&N cancer, recurrent disease, and benign post-treatment
      changes.
AB  - PURPOSE: To determine if dynamic contrast-enhanced (DCE)-magnetic resonance
      imaging (MRI) parameters such as permeability surface area (PS) and blood volume
      (BV) allow differentiating between new head and neck (HN) cancer, recurrent HN
      cancer, and post-treatment benign changes. METHOD: A total of 35 patients with
      newly diagnosed, recurrent, and benign post-treatment benign changes underwent
      DCE-MRI. PS and BV were calculated. RESULTS: PS values of the lesion were
      2.3*10(4)+/-5.8*10(4) for the newly diagnosed cancer group, 3.3*10(4)+/-1.7*10(4)
      for the recurrent cancer group, and 4.8*10(4)+/-8.1*10(4) for the post-treatment
      benign change group (P=.031). CONCLUSION: Post-treatment benign changes in the HN
      region had significantly high permeability property than newly diagnosed or
      previously treated recurrent tumor.

PMID- 25778389
TI  - Increased inflammatory potential of diet is associated with bone mineral density
      among postmenopausal women in Iran.
AB  - PURPOSE: Diet has been shown to be associated with bone mineral density (BMD);
      however, the inflammatory potential of diet in modulating BMD has not yet been
      studied. METHODS: We examined the association between a newly developed dietary
      inflammatory index (DII) and BMD in a sample of postmenopausal Iranian women. In
      this cross-sectional study, 160 postmenopausal women aged 50-85 years were
      studied and their femoral neck and lumbar spine BMDs were measured by dual-energy
      X-ray absorptiometry. The DII was computed based on dietary intake assessed using
      a previously validated, 168-item semiquantitative food frequency questionnaire.
      Logistic and linear regression models were fit to derive beta estimates and odds
      ratios (ORs), with DII fit as continuous and as a dichotomous variable. RESULTS:
      After adjusting for potential confounders, women with higher DII scores were more
      likely to have BMD below the median in the lumbar spine with the DII being used
      as both a continuous variable [ORcontinuous 1.64, 95 % confidence interval (CI)
      1.11-2.43, p value = 0.01; one-unit increase corresponding to ~17 % of its range
      in the current study] and a categorical variable (ORDII>-0.06/<= 2.30, 95 % CI
      1.05-5.07, p value = 0.04). Similar associations were observed when lumbar spine
      BMD was used as a continuous outcome. No significant association was observed
      with BMD in femoral neck, although the direction was along expected lines.
      CONCLUSION: These data suggest a pro-inflammatory diet, as indicated by
      increasing DII score, may be a risk factor for lower BMD in lumbar spine in
      postmenopausal Iranian women.

PMID- 25778390
TI  - Acinetobacter nosocomialis secretes outer membrane vesicles that induce
      epithelial cell death and host inflammatory responses.
AB  - Acinetobacter nosocomialis is an important nosocomial pathogen that causes a
      variety of opportunistic infections; however, pathogenesis of this microorganism
      has not yet been characterized. The aim of this study was to investigate the
      secretion of outer membrane vesicles (OMVs) from A. nosocomialis and to determine
      their cytotoxic effects and their ability to induce inflammatory responses both
      in vitro and in vivo by using human epithelial HEp-2 cells and a mouse model,
      respectively. A. nosocomialis ATCC 17903(T) secreted spherical OMVs when cultured
      in vitro. Proteomic analysis revealed that 147 different proteins were associated
      with A. nosocomialis OMVs and virulence-associated proteins, such as outer
      membrane protein A (OmpA), CsuA, CsuC, CsuD, PilW, hemolysin, and serine
      protease, were identified. A. nosocomialis OMVs were cytotoxic to HEp-2 cells.
      These vesicles also induced the expression of pro-inflammatory cytokine genes in
      the HEp-2 cells. Early inflammatory responses, such as congestion and focal
      neutrophilic infiltration, were observed in the lungs of mice injected with A.
      nosocomialis OMVs. In conclusion, A. nosocomialis OMVs are important secretory
      nanocomplexes that induce cytotoxicity of epithelial cells and host inflammatory
      responses, which may contribute to the pathogenesis of A. nosocomialis. 

PMID- 25778391
TI  - The distribution of pathogenic and toxigenic genes among MRSA and MSSA clinical
      isolates.
AB  - Staphylococcus aureus (S. aureus) is considered as a notorious nosocomial
      pathogen among hospitalized patients and community-dwelling subjects. Its
      increasing morbidity and mortality is believed to be due to antibiotic
      resistance. However, the data concerning molecular properties of infecting
      strains are few. In this study, a total of 192 S. aureus strains, including 88
      (45.8%) meticillin-sensitive S. aureus (MSSA) and 104 (54.2%) meticillin
      resistant S. aureus (MRSA) were recovered from clinical samples. The prevalence
      of subtypes containing staphylococcal cassette chromosome mec (SSCmec),
      staphylococcal enterotoxins (SEs), toxic shock syndrome toxin (TSST) and
      exfoliative toxin was assessed by PCR. Antibiotic susceptibility pattern and
      vancomycin resistance of each isolate were evaluated by disk diffusion method and
      micro-dilution method, respectively. 9 (2.3%) strains required MIC > 2 mg/l of
      vancomycin, which significantly increased among multi drug resistant (MDR), MRSA
      and SCCmec type III strains (p < 0.05). 171 (89%), 140 (72.91%), 7 (3.6), 78
      (48.6%), 5 (2.6%), 151 (78.64%), 129 (67.18%), 178 (92.7%) and 15 (7.8%) of 192
      isolates harbored mecA, entA, entB, entC, entD, entE, eta, etb and tsst-1 genes,
      respectively. 31 (16.14%), 5 (2.6%), 95 (49.48%) and 7 (3.64%) of 192 isolates
      carried SCCmec type I, II, III and IV, respectively. We found a significantly
      higher rate of MRSA and resistance to all tested antibiotics, except to
      penicillin G, kanamycin and linezolide among the SCCmec type III class (p <
      0.05). According to our findings, MSSA isolates should be taken as seriously as
      MRSA strains due to the potential presence of broad spectrum virulence factor
      genes. 

PMID- 25778393
TI  - Facile and sensitive detection of protamine by enhanced room-temperature
      phosphorescence of Mn-doped ZnS quantum dots.
AB  - Quantum dot (QD) nanohybrids provide an effective route to explore the new
      properties of materials and are increasingly used as highly valuable sensitive
      (bio) chemical probes. Interestingly, the room-temperature phosphorescence (RTP)
      of 3-mercaptopropionic acid (MPA)-capped Mn-doped ZnS QDs could be remarkably
      enhanced by the addition of protamine. Based on the above finding, a simple,
      sensitive, and selective method for rapid detection of protamine was successfully
      designed. With this method, protamine as a cationic peptide interacts
      electrostatically with MPA-capped Mn-doped ZnS QDs to form MPA-capped Mn-doped
      ZnS QD/protamine complexes, which leads to the aggregation of QDs and enhances
      the RTP intensity. Under the optimized conditions, the RTP intensity change was
      linearly proportional to the concentration of protamine in the range 0.2-3.0 MUg
      ml(-1), and the limit of detection was 0.14 MUg ml(-1). The proposed method was
      successfully applied to detect protamine in protamine sulfate injection and human
      serum samples with satisfactory results, and the recovery ranged from 96.5 to
      105.6%.

PMID- 25778392
TI  - A direct, ratiometric, and quantitative MALDI-MS assay for protein
      methyltransferases and acetyltransferases.
AB  - Protein methylation and acetylation play important roles in biological processes,
      and misregulation of these modifications is involved in various diseases.
      Therefore, it is critical to understand the activities of the enzymes responsible
      for these modifications. Herein we describe a sensitive method for ratiometric
      quantification of methylated and acetylated peptides via MALDI-MS by direct
      spotting of enzymatic methylation and acetylation reaction mixtures without
      tedious purification procedures. The quantifiable detection limit for peptides
      with our method is approximately 10 fmol. This is achieved by increasing the
      signal-to-noise ratio through the addition of NH4H2PO4 to the matrix solution and
      reduction of the matrix alpha-cyanohydroxycinnamic acid concentration to 2 mg/ml.
      We have demonstrated the application of this method in enzyme kinetic analysis
      and inhibition studies. The unique feature of this method is the simultaneous
      quantification of multiple peptide species for investigation of processivity
      mechanisms. Its wide buffer compatibility makes it possible to be adapted to
      investigate the activity of any protein methyltransferase or acetyltransferase.

PMID- 25778394
TI  - Sensitive detection of C-reactive protein in serum by immunoprecipitation
      microchip capillary gel electrophoresis.
AB  - Sepsis represents a significant cause of mortality in intensive care units. Early
      diagnosis of sepsis is essential to increase the survival rate of patients. Among
      others, C-reactive protein (CRP) is commonly used as a sepsis marker. In this
      work we introduce immune precipitation combined with microchip capillary gel
      electrophoresis (IP-MCGE) for the detection and quantification of CRP in serum
      samples. First high-abundance proteins (HSA, IgG) are removed from serum samples
      using affinity spin cartridges, and then the remaining proteins are labeled with
      a fluorescence dye and incubated with an anti-CRP antibody, and the
      antigen/antibody complex is precipitated with protein G-coated magnetic beads.
      After precipitation the complex is eluted from the beads and loaded onto the MCGE
      system. CRP could be reliably detected and quantified, with a detection limit of
      25 ng/MUl in serum samples and 126 pg/MUl in matrix-free samples. The overall
      sensitivity (LOQ = 75 ng/MUl, R(2) = 0.9668) of the method is lower than that of
      some specially developed methods (e.g., immune radiometric assay) but is
      comparable to those of clinically accepted ELISA methods. The straightforward
      sample preparation (not prone to mistakes), reduced sample and reagent volumes
      (including the antibodies), and high throughput (10 samples/3 h) are advantages
      and therefore IP-MCGE bears potential for point-of-care diagnosis.

PMID- 25778395
TI  - Head and neck and esophageal cancers after liver transplant: results from a
      multicenter cohort study. Italy, 1997-2010.
AB  - This study quantified the risk of head and neck (HN) and esophageal cancers in
      2770 Italian liver transplant (LT) recipients. A total of 186 post-transplant
      cancers were diagnosed-including 32 cases of HN cancers and nine cases of
      esophageal carcinoma. The 10-year cumulative risk for HN and esophageal carcinoma
      was 2.59%. Overall, HN cancers were nearly fivefold more frequent in LT
      recipients than expected (standardized incidence ratios - SIR=4.7, 95% CI: 3.2
      6.6), while esophageal carcinoma was ninefold more frequent (SIR=9.1, 95% CI: 4.1
      17.2). SIRs ranged from 11.8 in LT with alcoholic liver disease (ALD) to 1.8 for
      LT without ALD for HN cancers, and from 23.7 to 2.9, respectively, for esophageal
      carcinoma. Particularly elevated SIRs in LT with ALD were noted for carcinomas of
      tongue (23.0) or larynx (13.7). Our findings confirmed and quantified the large
      cancer excess risk in LT recipients with ALD. The risk magnitude and the
      prevalence of ALD herein documented stress the need of timely and specifically
      organized programs for the early diagnosis of cancer among LT recipients,
      particularly for high-risk recipients like those with ALD. 

PMID- 25778396
TI  - Integrins Influence the Size and Dynamics of Signaling Microclusters in a Pyk2
      dependent Manner.
AB  - Integrin engagement on lymphocytes initiates "outside-in" signaling that is
      required for cytoskeleton remodeling and the formation of the synaptic interface.
      However, the mechanism by which the "outside-in" signal contributes to receptor
      mediated intracellular signaling that regulates the kinetics of granule delivery
      and efficiency of cytolytic activity is not well understood. We have found that
      variations in ICAM-1 expression on tumor cells influence killing kinetics of
      these cells by CD16.NK-92 cytolytic effectors suggesting that changes in integrin
      ligation on the effector cells regulate the kinetics of cytolytic activity by the
      effector cells. To understand how variations of the integrin receptor ligation
      may alter cytolytic activity of CD16.NK-92 cells, we analyzed molecular events at
      the contact area of these cells exposed to planar lipid bilayers that display
      integrin ligands at different densities and activating CD16-specific antibodies.
      Changes in the extent of integrin ligation on CD16.NK-92 cells at the
      cell/bilayer interface revealed that the integrin signal influences the size and
      the dynamics of activating receptor microclusters in a Pyk2-dependent manner.
      Integrin-mediated changes of the intracellular signaling significantly affected
      the kinetics of degranulation of CD16.NK-92 cells providing evidence that
      integrins regulate the rate of target cell destruction in antibody-dependent cell
      cytotoxicity (ADCC). 

PMID- 25778397
TI  - Variable Region Identical IgA and IgE to Cryptococcus neoformans Capsular
      Polysaccharide Manifest Specificity Differences.
AB  - In recent years several groups have shown that isotype switching from IgM to IgG
      to IgA can affect the affinity and specificity of antibodies sharing identical
      variable (V) regions. However, whether the same applies to IgE is unknown. In
      this study we compared the fine specificity of V region-identical IgE and IgA to
      Cryptococcus neoformans capsular polysaccharide and found that these differed in
      specificity from each other. The IgE and IgA paratopes were probed by nuclear
      magnetic resonance spectroscopy with (15)N-labeled peptide mimetics of
      cryptococcal polysaccharide antigen (Ag). IgE was found to cleave the peptide at
      a much faster rate than V region-identical IgG subclasses and IgA, consistent
      with an altered paratope. Both IgE and IgA were opsonic for C. neoformans and
      protected against infection in mice. In summary, V-region expression in the
      context of the epsilon constant (C) region results in specificity changes that
      are greater than observed for comparable IgG subclasses. These results raise the
      possibility that expression of certain V regions in the context of alpha and
      epsilon C regions affects their function and contributes to the special
      properties of those isotypes. 

PMID- 25778398
TI  - The Proapoptotic F-box Protein Fbxl7 Regulates Mitochondrial Function by
      Mediating the Ubiquitylation and Proteasomal Degradation of Survivin.
AB  - Fbxl7, a component of the Skp1.Cul1.F-box protein type ubiquitin E3 ligase,
      regulates mitotic cell cycle progression. Here we demonstrate that overexpression
      of Fbxl7 in lung epithelia decreases the protein abundance of survivin, a member
      of the inhibitor of apoptosis family. Fbxl7 mediates polyubiquitylation and
      proteasomal degradation of survivin by interacting with Glu-126 within its
      carboxyl-terminal alpha helix. Furthermore, both Lys-90 and Lys-91 within
      survivin serve as ubiquitin acceptor sites. Ectopically expressed Fbxl7 impairs
      mitochondrial function, whereas depletion of Fbxl7 protects mitochondria from
      actions of carbonyl cyanide m-chlorophenylhydrazone, an inhibitor of oxidative
      phosphorylation. Compared with wild-type survivin, cellular expression of a
      survivin mutant protein deficient in its ability to interact with Fbxl7 (E126A)
      and a ubiquitylation-resistant double point mutant (KK90RR/KK91RR) rescued
      mitochondria to a larger extent from damage induced by overexpression of Fbxl7.
      Therefore, these data suggest that the Skp1.Cul1.F-box protein complex subunit
      Fbxl7 modulates mitochondrial function by controlling the cellular abundance of
      survivin. The results raise opportunities for F-box protein targeting to preserve
      mitochondrial function. 

PMID- 25778399
TI  - RhoGDIbeta Inhibits Bone Morphogenetic Protein 4 (BMP4)-induced Adipocyte Lineage
      Commitment and Favors Smooth Muscle-like Cell Differentiation.
AB  - The integration of signals involved in deciding the fate of mesenchymal stem
      cells is largely unknown. We used proteomics profiling to identify RhoGDIbeta, an
      inhibitor of the small G-protein Rho family, as a component that regulates
      commitment of C3H10T1/2 mesenchymal stem cells to the adipocyte or smooth muscle
      cell lineage in response to bone morphogenetic protein 4 (BMP4). RhoGDIbeta is
      notably down-regulated during BMP4-induced adipocytic lineage commitment of
      C3H10T1/2 mesenchymal stem cells, and this involves the cytoskeleton-associated
      protein lysyl oxidase. Excess RhoGDIbeta completely prevents BMP4-induced
      commitment to the adipocyte lineage and simultaneously stimulates smooth muscle
      cell commitment by suppressing the activation of Rac1. Overexpression of
      RhoGDIbeta induces stress fibers of F-actin by a process involving phosphomyosin
      light chain, indicating that cytoskeletal tension regulated by RhoGDIbeta
      contributes to determining adipocyte versus myocyte commitment. Furthermore, the
      overexpression of RacV12 (constitutively active form of Rac1) totally rescues the
      inhibition of adipocyte commitment by RhoGDIbeta, simultaneously preventing
      formation of the smooth muscle-like phenotype and disrupting the stress fibers in
      cells overexpressing RhoGDIbeta. Collectively, these results indicate that
      RhoGDIbeta functions as a novel BMP4 signaling target that regulates adipogenesis
      and myogensis. 

PMID- 25778400
TI  - Targeted Disruption of Ig-Hepta/Gpr116 Causes Emphysema-like Symptoms That Are
      Associated with Alveolar Macrophage Activation.
AB  - Ig-Hepta/GPR116 is a member of the G protein-coupled receptor family
      predominantly expressed in the alveolar type II epithelial cells of the lung.
      Previous studies have shown that Ig-Hepta is essential for lung surfactant
      homeostasis, and loss of its function results in high accumulation of surfactant
      lipids and proteins in the alveolar space. Ig-Hepta knock-out (Ig-Hepta(-/-))
      mice also exhibit emphysema-like symptoms, including accumulation of foamy
      alveolar macrophages (AMs), but its pathogenic mechanism is unknown. Here, we
      show that the bronchoalveolar lavage fluid obtained from Ig-Hepta(-/-) mice
      contains high levels of inflammatory mediators, lipid hydroperoxides, and matrix
      metalloproteinases (MMPs), which are produced by AMs. Accumulation of reactive
      oxygen species was observed in the AMs of Ig-Hepta(-/-) mice in an age-dependent
      manner. In addition, nuclear factor-kappaB (NF-kappaB) is activated and
      translocated into the nuclei of the AMs of Ig-Hepta(-/-) mice. Release of MMP-2
      and MMP-9 from the AMs was strongly inhibited by treatment with inhibitors of
      oxidants and NF-kappaB. We also found that the level of monocyte chemotactic
      protein-1 is increased in the embryonic lungs of Ig-Hepta(-/-) mice at 18.5 days
      postcoitum, when AMs are not accumulated and activated. These results suggest
      that Ig-Hepta plays an important role in regulating macrophage immune responses,
      and its deficiency leads to local inflammation in the lung, where AMs produce
      excessive amounts of reactive oxygen species and up-regulate MMPs through the NF
      kappaB signaling pathway. 

PMID- 25778401
TI  - Suppression of RIP3-dependent necroptosis by human cytomegalovirus.
AB  - Necroptosis is an alternate programmed cell death pathway that is unleashed by
      caspase-8 compromise and mediated by receptor-interacting protein kinase 3
      (RIP3). Murine cytomegalovirus (CMV) and herpes simplex virus (HSV) encode
      caspase-8 inhibitors that prevent apoptosis together with competitors of RIP
      homotypic interaction motif (RHIM)-dependent signal transduction to interrupt the
      necroptosis. Here, we show that pro-necrotic murine CMV M45 mutant virus drives
      virus-induced necroptosis during nonproductive infection of RIP3-expressing human
      fibroblasts, whereas WT virus does not. Thus, M45-encoded RHIM competitor, viral
      inhibitor of RIP activation, sustains viability of human cells like it is known
      to function in infected mouse cells. Importantly, human CMV is shown to block
      necroptosis induced by either TNF or M45 mutant murine CMV in RIP3-expressing
      human cells. Human CMV blocks TNF-induced necroptosis after RIP3 activation and
      phosphorylation of the mixed lineage kinase domain-like (MLKL) pseudokinase. An
      early, IE1-regulated viral gene product acts on a necroptosis step that follows
      MLKL phosphorylation prior to membrane leakage. This suppression strategy is
      distinct from RHIM signaling competition by murine CMV or HSV and interrupts an
      execution process that has not yet been fully elaborated. 

PMID- 25778402
TI  - The Radical S-Adenosyl-L-methionine Enzyme QhpD Catalyzes Sequential Formation of
      Intra-protein Sulfur-to-Methylene Carbon Thioether Bonds.
AB  - The bacterial enzyme designated QhpD belongs to the radical S-adenosyl-L
      methionine (SAM) superfamily of enzymes and participates in the post
      translational processing of quinohemoprotein amine dehydrogenase. QhpD is
      essential for the formation of intra-protein thioether bonds within the small
      subunit (maturated QhpC) of quinohemoprotein amine dehydrogenase. We overproduced
      QhpD from Paracoccus denitrificans as a stable complex with its substrate QhpC,
      carrying the 28-residue leader peptide that is essential for the complex
      formation. Absorption and electron paramagnetic resonance spectra together with
      the analyses of iron and sulfur contents suggested the presence of multiple
      (likely three) [4Fe-4S] clusters in the purified and reconstituted QhpD. In the
      presence of a reducing agent (sodium dithionite), QhpD catalyzed the multiple
      turnover reaction of reductive cleavage of SAM into methionine and 5'
      deoxyadenosine and also the single-turnover reaction of intra-protein sulfur-to
      methylene carbon thioether bond formation in QhpC bound to QhpD, producing a
      multiknotted structure of the polypeptide chain. Homology modeling and mutagenic
      analysis revealed several conserved residues indispensable for both in vivo and
      in vitro activities of QhpD. Our findings uncover another challenging reaction
      catalyzed by a radical SAM enzyme acting on a ribosomally translated protein
      substrate.

PMID- 25778403
TI  - Lipoprotein(a) catabolism is regulated by proprotein convertase subtilisin/kexin
      type 9 through the low density lipoprotein receptor.
AB  - Elevated levels of lipoprotein(a) (Lp(a)) have been identified as an independent
      risk factor for coronary heart disease. Plasma Lp(a) levels are reduced by
      monoclonal antibodies targeting proprotein convertase subtilisin/kexin type 9
      (PCSK9). However, the mechanism of Lp(a) catabolism in vivo and the role of PCSK9
      in this process are unknown. We report that Lp(a) internalization by hepatic
      HepG2 cells and primary human fibroblasts was effectively reduced by PCSK9.
      Overexpression of the low density lipoprotein (LDL) receptor (LDLR) in HepG2
      cells dramatically increased the internalization of Lp(a). Internalization of
      Lp(a) was markedly reduced following treatment of HepG2 cells with a function
      blocking monoclonal antibody against the LDLR or the use of primary human
      fibroblasts from an individual with familial hypercholesterolemia; in both cases,
      Lp(a) internalization was not affected by PCSK9. Optimal Lp(a) internalization in
      both hepatic and primary human fibroblasts was dependent on the LDL rather than
      the apolipoprotein(a) component of Lp(a). Lp(a) internalization was also
      dependent on clathrin-coated pits, and Lp(a) was targeted for lysosomal and not
      proteasomal degradation. Our data provide strong evidence that the LDLR plays a
      role in Lp(a) catabolism and that this process can be modulated by PCSK9. These
      results provide a direct mechanism underlying the therapeutic potential of PCSK9
      in effectively lowering Lp(a) levels. 

PMID- 25778405
TI  - Positive Body Image and Sexual Functioning in Dutch Female University Students:
      The Role of Adult Romantic Attachment.
AB  - This study focused on links between romantic attachment, positive body image, and
      sexual functioning. Dutch female university students (N = 399) completed an
      online survey that included self-report items about body appreciation, sexual
      functioning, and romantic attachment. A proposed conceptual model was tested
      using structural equation modeling and a good fit to the data was found. Results
      revealed that attachment avoidance in a romantic context was negatively related
      to sexual arousal, vaginal lubrication, the ability to reach orgasm, and sexual
      satisfaction. Attachment anxiety was negatively related to body appreciation
      which, in turn, was positively related to sexual desire and arousal. Findings
      indicated that romantic attachment is meaningfully linked to body appreciation
      and sexual functioning. Therefore, the concept of adult attachment may be a
      useful tool for the treatment of sexual problems of young women.

PMID- 25778406
TI  - Looking back and forward at natural orifice translumenal endoscopic surgery.

PMID- 25778407
TI  - [Calcifying fibrous tumor of the small bowel].

PMID- 25778404
TI  - The Early Metazoan Trichoplax adhaerens Possesses a Functional O-GlcNAc System.
AB  - Protein O-GlcNAcylation is a reversible post-translational signaling modification
      of nucleocytoplasmic proteins that is essential for embryonic development in
      bilateria. In a search for a reductionist model to study O-GlcNAc signaling, we
      discovered the presence of functional O-GlcNAc transferase (OGT), O-GlcNAcase
      (OGA), and nucleocytoplasmic protein O-GlcNAcylation in the most basal extant
      animal, the placozoan Trichoplax adhaerens. We show via enzymatic
      characterization of Trichoplax OGT/OGA and genetic rescue experiments in
      Drosophila melanogaster that these proteins possess activities/functions similar
      to their bilaterian counterparts. The acquisition of O-GlcNAc signaling by
      metazoa may have facilitated the rapid and complex signaling mechanisms required
      for the evolution of multicellular organisms. 

PMID- 25778409
TI  - [Risk factors for mortality in patients with chronic obstructive pulmonary
      disease].
AB  - OBJECTIVE: To identify risk factors of mortality in patients with chronic
      obstructive pulmonary disease (COPD). DESIGN: A retrospective cohort study.
      LOCATION: Primary care setting in Lleida, Spain. PARTICIPANTS: 2.501 patients
      older than 40 years with at least a spirometry in the 24 months prior to the
      beginning of the study were followed for 3 years. MAIN MEASUREMENTS: The
      dependent variable was the overall mortality in the period 11/01/2010-10/31/2013;
      and the independents: spirometric parameters, severity (GOLD) and clinical
      variables. Their association with mortality was analyzed by calculating the
      adjusted odds ratio using a non-conditional logistic regression model. RESULTS:
      The average age of 2.501 patients at the beginning of the study was 68.4 years
      (SD=11.6). 75.0% were males. 50.8% had a mild severity COPD, followed by moderate
      (35.3%), severe (9.4%) and very severe (4.4%). Mortality rate for the all period
      was 12.55%. The variables of the predictive model were: age, male sex, previous
      exacerbations, number of visits to primary care, comorbidity, smoking, severity
      of COPD (GOLD) and not receiving influenza vaccination, with an area under the
      ROC curve of 0.76. CONCLUSIONS: This model, easy and quick to apply, would
      identify those patients at increased risk of mortality and who could benefit from
      preventive strategies to improve their survival.

PMID- 25778408
TI  - Not all biofluids are created equal: chewing over salivary diagnostics and the
      epigenome.
AB  - PURPOSE: This article describes progress to date in the characterization of the
      salivary epigenome and considers the importance of previous work in the salivary
      microbiome, proteome, endocrine analytes, genome, and transcriptome. METHODS:
      PubMed and Web of Science were used to extensively search the existing literature
      (original research and reviews) related to salivary diagnostics and biomarker
      development, of which 125 studies were examined. This article was derived from
      the most relevant 74 sources highlighting the recent state of the evolving field
      of salivary epigenomics and contributing significantly to the foundational work
      in saliva-based research. FINDINGS: Validation of any new saliva-based diagnostic
      or analyte will require comparison to previously accepted standards established
      in blood. Careful attention to the collection, processing, and analysis of
      salivary analytes is critical for the development and implementation of newer
      applications that include genomic, transcriptomic, and epigenomic markers. All
      these factors must be integrated into initial study design. IMPLICATIONS: This
      commentary highlights the appeal of the salivary epigenome for translational
      applications and its utility in future studies of development and the interface
      among environment, disease, and health.

PMID- 25778410
TI  - Survival probabilities at spherical frontiers.
AB  - Motivated by tumor growth and spatial population genetics, we study the interplay
      between evolutionary and spatial dynamics at the surfaces of three-dimensional,
      spherical range expansions. We consider range expansion radii that grow with an
      arbitrary power-law in time: R(t) = R0(1 + t/t(*))Theta, where Theta is a growth
      exponent, R0 is the initial radius, and t(*) is a characteristic time for the
      growth, to be affected by the inflating geometry. We vary the parameters t(*) and
      Theta to capture a variety of possible growth regimes. Guided by recent results
      for two-dimensional inflating range expansions, we identify key dimensionless
      parameters that describe the survival probability of a mutant cell with a small
      selective advantage arising at the population frontier. Using analytical
      techniques, we calculate this probability for arbitrary Theta. We compare our
      results to simulations of linearly inflating expansions (Theta = 1 spherical
      Fisher-Kolmogorov-Petrovsky-Piscunov waves) and treadmilling populations (Theta =
      0, with cells in the interior removed by apoptosis or a similar process). We find
      that mutations at linearly inflating fronts have survival probabilities enhanced
      by factors of 100 or more relative to mutations at treadmilling population
      frontiers. We also discuss the special properties of "marginally inflating"
      (Theta = 1/2) expansions.

PMID- 25778411
TI  - Visualization of water transport into soybean nodules by Tof-SIMS cryo system.
AB  - This paper examined the route of water supply into soybean nodules through the
      new visualization technique of time of flight secondary ion mass spectrometry
      (Tof-SIMS) cryo system, and obtained circumstantial evidence for the water inflow
      route. The maximum resolution of the Tof-SIMS imaging used by this study was 1.8
      MUm (defined as the three pixel step length), which allowed us to detect water
      movement at the cellular level. Deuterium-labeled water was supplied to soybean
      plants for 4h and the presence of deuterium in soybean nodules was analyzed by
      the Tof-SIMS cryo system. Deuterium ions were found only in the endodermis tissue
      surrounding the central cylinder in soybean nodules. Neither xylem vessels nor
      phloem complex itself did not indicate any deuterium accumulation. Deuterium-ion
      counts in the endodermis tissue were not changed by girdling treatment, which
      restricted water movement through the phloem complex. The results strongly
      indicated that nodule tissues did not receive water directly from the phloem
      complex, but received water through root cortex apoplastic pathway from the root
      axis.

PMID- 25778412
TI  - Heat shock protein 90 acts in brassinosteroid signaling through interaction with
      BES1/BZR1 transcription factor.
AB  - Brassinosteroids (BRs), a class of phytohormones, control various physiological
      and developmental processes in plants. Two highly homologous transcription
      factors, brassinosteroid insensitive 1-EMS-SUPRESSOR 1 (BES1) and brassinazole
      resistant 1 (BZR1), act downstream of BR signaling to control several thousands
      of putative target genes. We reported previously that BES1 forms a complex with a
      molecular chaperone: heat shock protein 90 (HSP90). This study demonstrates that
      the amino-terminal and central parts of BES1 are responsible for its physical
      interaction with HSP90.3 in vitro. Additionally, we present evidence that BZR1 is
      a novel HSP90 partner aside from two BR signaling components previously
      identified as its clients: BES1 and brassinosteroid insensitive 2 (BIN2).
      Furthermore, geldanamycin, an inhibitor of ATPase activity in HSP90, caused BES1
      hyperphosphorylation and disrupted the expression of BR-responsive genes.
      Considered together, our results imply that HSP90 takes a part in BR-mediated
      gene expression through complex formation with two major transcription factors.

PMID- 25778413
TI  - The different expression profiles of microRNAs in elderly and young human dental
      pulp and the role of miR-433 in human dental pulp cells.
AB  - As a kind of endogenous noncoding small RNA, MicroRNA (miRNA) plays important
      roles of regulation to various physiological functions, while its affections on
      senescence of human dental pulp cell (HDPCs) are still unknown. Thus, we
      identified the senescence-associated miRNAs in HDPCs by microarray analysis,
      predicted their targets and regulatory signaling pathway by gene ontology and
      Kyoto encyclopedia of genes and genomes pathway database analysis. After
      validated, the senescence-associated miRNAs' expression level was up- and down
      regulated using lentivirus package and cell transfection to find its role in
      HDPCs' morphology, proliferation, apoptosis, and mineralization. The results
      showed 27 miRNAs differentially expressed at least 1.5-fold, of which 16 were up
      regulated and 11 down-regulated, the function of their targets was mainly focused
      on signal transduction, cell proliferation, apoptosis, and transcription
      regulation. According to the change fold, we speculated that miR-433 could be one
      of the vital senescence-associated miRNAs of HDPCs and found its target (GRB2),
      validated that miR-433 could negatively regulate GRB2 and the RAS-MAPK signaling
      pathway, leading to the decline of proliferation and mineralization ability of
      HDPCs and the acceleration of cell apoptosis, suggesting the regulation of miR
      433 might be the potential target to promote repair and regeneration of HDPCs in
      the elderly.

PMID- 25778414
TI  - ERCP in a cohort of 759 cases: A 6-year experience of a single tertiary centre in
      Libya.
AB  - BACKGROUND AND STUDY AIMS: The aim of this study was to review the indications,
      findings, technical success, and outcomes of endoscopic retrograde
      cholangiopancreatography (ERCP) procedures in a large cohort of patients admitted
      to a single tertiary centre in Libya. PATIENTS AND METHODS: A total of 759
      consecutive ERCP procedures were performed in 704 patients from January 2005
      through December 2010 at the Endoscopy Unit of Central Hospital, Tripoli, Libya.
      The patients' demographic characteristics, clinical information, ERCP
      indications, laboratory parameters, and post-ERCP complications were reviewed.
      Formal written consent was obtained from all patients prior to each procedure.
      RESULTS: The study included 280 (36.9%) males and 479 (63.1%) females with mean
      age +/- standard deviation (SD) of 56.8 +/- 18.7 years. Papillotomy was performed
      in 670 (88.3%) cases of the ERCP procedures. Common bile duct (CBD) stones were
      reported in 389 (51.3%) cases and were more frequent in females (234 cases,
      60.1%) than males (155, 39.9%) (p = 0.01). The majority of the CBD stones were
      successfully retrieved with balloon extraction (304 cases, 78.2%), while
      mechanical lithotripsy (67 cases, 17.2%) and Dormia basket (11 cases, 2.8%) were
      used for difficult stones. Only seven (1.8%) cases were referred for surgery.
      Malignancy was found in 151 (19.9%) of the cases and was significantly more
      common in males than females (102, 67.5% vs. 49, 32.5%, respectively, p = 0.001).
      Stents for bile drainage were inserted in 26 (17.2%) of these cases. The
      complications encountered were acute pancreatitis in 30 cases (3.9%), minor
      bleeding in nine cases (1.2%), major bleeding in one case (0.15%), cholangitis in
      four cases (0.52%), and perforation in one case (0.15). Mortality was reported in
      three cases (0.4%). CONCLUSION: The ERCP indications and the related
      complications, in our centre in Libya, are comparatively consistent with those
      reported data in other countries. Successful biliary cannulation was achieved in
      most of the patients, and post-ERCP complications were uncommon except for
      pancreatitis, which occurred more frequently.

PMID- 25778415
TI  - Persistent conditioned place preference to cocaine and withdrawal hypo-locomotion
      to mephedrone in the flatworm planaria.
AB  - The purpose of the present study was to determine the effects of exposure to
      cocaine and mephedrone on conditioned place preference (CPP) and locomotion in
      the flatworm planaria. Planaria were treated with either cocaine or mephedrone at
      1 or 10 MUM. Planaria were exposed to 15 min of drug in their non-preferred place
      (either a rough- or smooth-floored petri dish) on alternate days, and were
      exposed to normal water in their preferred place on the following day. There were
      5 days of conditioning to drug. Planaria were then tested for CPP on day 2, 6 and
      13 after withdrawal. We found that animals exhibited CPP to cocaine at both 1 and
      10 MUM, but not to mephedrone. When examining locomotor activity we found that
      neither cocaine nor mephedrone treatment showed any evidence of evoking increased
      motility or locomotor sensitisation. Hypo-motility was seen on the first day of
      conditioning at concentrations of 10 MUM for both cocaine and mephedrone, but had
      disappeared by the last day of conditioning. Examining chronic withdrawal, only
      10 MUM mephedrone had a significant effect on motility, decreasing locomotion on
      day 2 of withdrawal. Taken together we have shown that cocaine evoked CPP in
      planaria. We have also shown withdrawal depressing effects of mephedrone on
      motility.

PMID- 25778416
TI  - Neurogenesis and precursor cell differences in the dorsal and ventral adult
      canine hippocampus.
AB  - During evolution a unique anterior-posterior flexure posited the canine dentate
      gyrus in two distinct dorsal and ventral positions. We therefore sought to
      explore neurogenesis and neurogenic cell-related difference along the canine
      hippocampal dorsal-ventral axis. Post mortem histological analysis revealed 49.1%
      greater doublecortin (DCX)-positive cells and a 158.5% greater percentage of
      double labeled DCX-positive/neuronal nuclei (NeuN) positive cells in the dorsal
      subgranular zone compared to the ventral. We then show neural precursor cells
      isolated from fresh hippocampal tissue are capable of proliferating long term,
      and after differentiation, express neuronal and glial markers. Dorsal hippocampal
      isolates produced a 120.0% higher frequency of sphere-forming neural precursor
      cells compared to ventral hippocampal tissue. Histological DCX and neurosphere
      assay results were highly correlated. Overall, we provide the first evidence that
      the dorsal canine hippocampus has a markedly higher rate of adult neurogenesis
      than the ventral hippocampus, possibly related to a greater frequency of
      contributory neural precursor cells. 

PMID- 25778417
TI  - Brain morphometry and electrophysiological recordings in relation to illness
      duration in schizophrenia.
AB  - Schizophrenia has been recently increasingly linked with a number of structural
      brain morphological changes which can be associated with functional deficiencies.
      The aim of this study is to relate electrophysiological changes with structural
      changes of Heschl's gyrus (HG) volume in schizophrenia. Fifteen schizophrenia
      patients were compared with control group by magnetic resonance imaging (MRI)
      volumetry and auditory evoked potentials. A significantly lower bilateral HG
      volumes and a significantly lower global field power value of the N1P2 component
      were detected in the schizophrenia group. The auditory evoked potentials have
      been used as a functional correlate that displayed a significant amplitude
      reduction that matched the reduction in the HG volume with the chronicity of the
      disease. This trend may be utilized as a vehicle to assess follow-up of the
      disorder by means of MRI and electrophysiology. 

PMID- 25778418
TI  - Involvement of norepinephrine and serotonin system in antidepressant-like effects
      of oleoylethanolamide in the mice models of behavior despair.
AB  - Oleoylethanolamide (OEA) is an endocannabinoid analogy that belongs to a family
      of endogenous acylethanolamides. Increasing evidence suggests that OEA may act as
      an endogenous neuroprotective factor and participate in the control of mental
      disorder-related behaviors. In the present study, we investigated the
      antidepressant- like potential of OEA in mice in comparison with clomipramine
      (Cp). 50 mice were randomly divided into 5 groups, and treated with a vehicle
      (0.3% methyl cellulose, 20 mL/kg, p.o.), OEA (2.5, 5-10mg/kg, p.o.), or Cp
      (10mg/kg, p.o.) for 7 days. The immobility was used to evaluate depressive-like
      behaviors in tail suspension test (TST) and forced swimming test (FST). ELISA
      detected changes in cerebral noradrenaline (NE) and serotonin (5-HT) levels.
      Likewise, in the drug-induced model of depression, OEA was given once daily at
      10mg/kg (p.o.) for 7 consecutive days. Then, the mice received reserpine (4
      mg/kg, i.p.) and the rectal temperature was measured at different time points.
      Consequently, head twitch behavior induced by intraperitoneal injection of 5
      hydroxy-tryptophan (5-HTP; 300 mg/kg) were determined. The experimental data
      showed that OEA (2.5-10mg/kg) treatment significantly decreased the immobility as
      compared to the control group, and OEA (10mg/kg) treatment significantly
      increased 5-HTP-induced head twitch behavior and reversed reserpine-induced
      hypothermia and increased cerebral levels of NE and 5-HT. Thus, the
      antidepressant effects of OEA may be related to regulating central monoamine
      neurotransmitters.

PMID- 25778419
TI  - Specific gene expression in mouse cortical astrocytes is mediated by a 1740bp
      GFAP promoter-driven combined adeno-associated virus 2/5/7/8/9.
AB  - We sought to demonstrate the in vivo transduction efficiency and tropism range in
      astrocytes of a combined-serotype adeno associated virus (AAV2/5/7/8/9). To
      control expression of enhanced green fluorescent protein (EGFP), a 1740bp glial
      fibrillary acidic protein (GFAP) promoter was obtained and ligated into vectors
      of each AAV serotype (2/5/7/8/9). Purified AAVs were then injected into the
      somatosensory cortex of C57BL/6J mice. Cell-type specific antibodies and
      subsequent immunofluorescence were used to identify astrocytes (GFAP), neurons
      (neuronal nuclear antigen, NeuN), microglia (ionized calcium-binding adapter
      molecule 1, Iba1), and oligodendrocytes (myelin basic protein, MBP), whereby,
      EGFP expression was measured in each cell type at 1-4 weeks post-injection. Our
      results indicated that the majority of astrocytes expressed EGFP, while only a
      small number of neurons expressed EGFP. Both microglia and oligodendrocytes
      lacked EGFP expression after viral injection. Quantitative analyses revealed that
      the percentage of EGFP-positive astrocytes was about 98% after viral injection,
      while the EGFP-positive neuronal percentage was less than 2%. Thus, this study
      shows that using a combined-serotype AAV carrying a 1740bp GFAP promoter results
      in successful, cell-type specific infection of the central nervous system, with
      robust gene expression in murine astrocytes. 

PMID- 25778420
TI  - Study on the growth and photosynthetic characteristics of wheat seedlings under
      [C4mim][OAc] (1-butyl-3-methyl-imidazolium acetate) with Cd2+ stress.
AB  - In this paper, the joint effect of 0.5 mmol.L(-1) Cd(2+) and various
      concentrations (50-400 mg.L(-1)) of the ionic liquid 1-butyl-3-methyl-imidazolium
      acetate ([C4min][OAc]) on the growth and photosynthetic performance of wheat
      seedlings in hydroponic culture was investigated. Seedlings grown in presence of
      Cd(2+) and [C4min][OAc] showed significant (p < 0.05) improvement in growth
      (shoot and root lengths and dry weights) and photosynthetic performance
      (photosynthetic rate, stomatal conductance, transpiration rate, and chlorophyll a
      but not chlorophyll b) compared to seedlings grown in the presence of Cd(2+) but
      without [C4min][OAc]. However, this only happened under the lower range of
      [C4min][OAc] concentrations (50-200 mg.L(-1)). In addition, significant reduction
      in the level of Cd(2+) was also observed in the leaf tissue of wheat seedlings
      grown in the presence of 0.5 mmol.L(-1) Cd(2+) and 100 mg.L(-1) [C4min][OAc].
      Overall, Cd(2+) exerted a stronger inhibition than [C4min][OAc] on the growth and
      photosynthetic performance of wheat seedlings. However, when both Cd(2+) and
      [C4min][OAc] were present in the culture, the toxicity of Cd(2+) could be
      mitigated by lower concentrations of [C4mim][OAc]. This phenomenon could be due
      to [C4mim][OAc] forming metal complexes with Cd(2+), thus reducing the toxicity
      of Cd(2+).

PMID- 25778421
TI  - Ras ssDNA aptamer inhibits vascular smooth muscle cell proliferation and
      migration through MAPK and PI3K pathways.
AB  - Proliferation and migration of vascular smooth muscle cells (VSMCs) mediated by
      Ras proteins are crucial in restenosis following percutaneous coronary
      intervention (PCI) and coronary artery bypass graft (CABG). In this study, a
      novel, single-stranded DNA (ssDNA) aptamer designated as Ras-a1 with high
      affinity and specificity to human Ras protein was isolated using systematic
      evolution of ligands by exponential enrichment. Ras-a1 was delivered into VSMCs
      by electroporation using one square waveform of 200 V for 20 msec. Proliferation
      of VSMCs was determined using a cell counting kit-8 assay, which revealed the
      maximal inhibitory rate (40%) was obtained at 24 h after Ras-a1 transfection. The
      migration of VSMCs, determined using a Transwell assay, was significantly
      inhibited in Rasa1 cells in a time-dependent manner. To investigate the potential
      mechanisms of transfected Ras-a1 on the migration and proliferation of VSMCs, the
      phosphorylation of MEK1/2, ERK1/2, and Akt was determined using western blot
      analysis, which showed that a marked downregulation was observed in the
      phosphorylation of MEK1/2, ERK1/2, and Akt following the delivery of Ras-a1. This
      result demonstrated that Ras-a1 inhibits the proliferation and migration of VSMCs
      by inhibiting the phosphorylation of Ras and interrupting signal transduction in
      the Ras-MEK1/2-ERK1/2 and phosphoinositide-3 kinase/Akt pathways. The novel Ras
      protein-targeted ssDNA aptamer selected may be applicable for the prevention of
      restenosis after PCI and CABG.

PMID- 25778422
TI  - Diagnosis and Ablation of Long RP Supraventricular Tachycardias.
AB  - OPINION STATEMENT: Long RP tachycardias are a unique collection of arrhythmias
      that include atypical (fast-slow) atrio-ventricular nodal reentrant tachycardia
      (AVNRT) with and without a concealed, bystander nodo-fascicular/ventricular
      accessory pathway (AP), orthodromic reciprocating tachycardia (ORT) using a
      concealed, slowly conducting, and decremental atrio-ventricular (AV) AP (PJRT),
      ORT using a concealed nodo-fascicular/ventricular AP (NFRT), and atrial
      tachycardia (AT)-all but the last being dependent upon the AV node. These
      tachycardias respond differently to pacing maneuvers than their short RP
      counterparts and can manifest: (1) both true and pseudo-AAV responses, (2) long
      uncorrected and corrected post-pacing intervals, (3) prolonged delta ventriculo
      atrial (?VA) and delta His bundle-atrial (?HA) values, and (4) resetting with
      delay. Diagnosis requires analysis of available clues from spontaneous transition
      zones as well as atrial and ventricular pacing maneuvers to delineate the upper
      and lower limbs of each circuit, respectively. Establishing the exact mechanism
      of tachycardia is important for safe and successful ablation. With activation
      mapping to localize AT or the AV AP of ORT and slow pathway (SP) ablation of
      atypical AVNRT and NF APs inserting into the SP, the majority of long RP
      tachycardias can be successfully treated.

PMID- 25778423
TI  - Mechanisms Underlying AF: Triggers, Rotors, Other?
AB  - OPINION STATEMENT: There is ongoing debate regarding the precise mechanisms
      underlying atrial fibrillation (AF). An improved understanding of these
      mechanisms is urgently needed to improve interventional strategies to suppress
      and eliminate AF, since the success of current strategies is suboptimal. At
      present, guidelines for AF ablation focus on pulmonary vein (PV) isolation for
      the prevention of arrhythmia. Additional targets are presently unclear, and
      include additional linear ablation and electrogram-guided substrate modification,
      without clear mechanistic relevance. PV and non-PV triggers are likely central in
      the first few seconds of AF initiation. Rapid activation from such triggers
      interacts with transitional mechanisms including conduction velocity slowing,
      action potential duration (APD) alternans, and steep APD restitution to cause
      conduction block and initiate functional reentry. However, complete suppression
      of potential triggers has proven elusive, and the intra-procedural mapping and
      targeting of transitional mechanisms has not been reported. A growing body of
      research implicates electrical rotors and focal sources as central mechanisms for
      the maintenance of AF. In several recent series, they were observed in nearly all
      patients with sustained arrhythmia. Ablation of rotor and focal source sites,
      prior to pulmonary vein isolation, substantially modulated atrial fibrillation in
      a high proportion of patients, and improved ablation outcomes versus pulmonary
      vein isolation alone. These results have subsequently been confirmed in
      multicenter series, and the improved outcomes have been found to persist to a
      mean follow-up of 3 years. Recently, rotors have been observed by multiple groups
      using diverse technologies. These findings represent a paradigm shift in AF,
      focusing on sustaining mechanisms, as is currently done with other arrhythmias
      such as atrioventricular node reentrant tachycardia. Studies are currently
      underway to assess the optimal strategy for the application of rotor-based
      ablation in AF management, including clinical trials on the relative efficacy of
      rotor-only ablation versus PVI-only ablation, which will inform future practice
      guidelines.

PMID- 25778424
TI  - Honing in on optimal ventricular pacing sites: an argument for his bundle pacing.
AB  - OPINION STATEMENT: Frequent ventricular pacing is often or completely unavoidable
      in patients with high-grade or complete heart block. Over time, patients with
      high-burden RV pacing are at risk for developing symptomatic cardiomyopathy due
      to pacing-induced ventricular dyssynchrony. Growing awareness of this concern has
      generated interest in alternative pacing sites like the septum and outflow tract,
      the thinking being that these sites will more closely mimic His-Purkinje-mediated
      ventricular activation. Numerous studies have met with mixed results likely due
      to the fact that-to quote Marvin Gaye-there ain't nothing like the real thing.
      Herein lies the advantage of His bundle pacing (HBP), as it is the only pacing
      modality capable of physiological ventricular activation. HBP has been
      demonstrated to be safe and reliable in various forms of AV block with minimal
      drawbacks, namely modestly higher pacing thresholds when compared with other RV
      sites. Additionally, HBP is a truly physiologic alternative to biventricular
      pacing to effect cardiac resynchronization therapy (CRT), a concept supported by
      small observational and prospective studies. In our view, His bundle pacing
      should be considered in nearly all patients requiring ventricular pacing.

PMID- 25778425
TI  - Intravenous thrombolysis for acute stroke: current standards and future
      directions.
AB  - OPINION STATEMENT: Intravenous thrombolysis with the recombinant tissue
      plasminogen activator alteplase is the standard of care for patients with acute
      ischaemic stroke presenting within 4.5 h of symptom onset. The odds of
      independent survival decline steeply with longer time to treatment delivery,
      reflecting progressive ischaemic damage to the brain. Standards accordingly
      emphasise optimisation of patient pathways to minimise treatment delays.
      Observational data and international clinical guidelines support the safety and
      efficacy of alteplase in many patient groups currently excluded from treatment
      (e.g. seizure at onset, concomitant diabetes and previous stroke) on the basis of
      historical clinical trial criteria. Future evolution of thrombolysis will
      optimise dosing, apply advanced imaging to extend treatment to groups currently
      excluded and investigate novel drugs, and adjunctive drug and device therapies.
      To date, trials of novel therapeutic approaches that have been applied at later
      time points have failed to demonstrate benefit, suggesting that the future gains
      are likely to arise from applications within current time windows.

PMID- 25778426
TI  - Statins in the prevention of contrast-induced nephropathy.
AB  - OPINION STATEMENT: Coronary angiography and percutaneous coronary interventions
      are common procedures that utilize iodinated contrast medium to visualize the
      coronary arterial tree and treat stable and unstable ischemic heart syndromes.
      Exposure to contrast agents can cause acute and persistent worsening of renal
      function leading to increased morbidity and mortality. Certain patient
      characteristics such as age, presence of diabetes, congestive heart failure,
      chronic kidney disease, hemodynamic instability on presentation, and type and
      volume of contrast used can increase the risk of developing contrast-induced
      nephropathy (CIN) and its subsequent complications. Despite the lack of a
      universal definition, CIN is typically defined as an increase in serum creatinine
      >=0.5 mg/dL or 25 % above baseline 48 to 72 h after contrast exposure. Previous
      research has shown the benefits of adequate intravenous hydration with iso
      osmolar crystalloids and the importance of limiting the amount of low-osmolar and
      iso-osmolar contrast used to prevent the development of CIN. 3-hydroxy-3
      methylglutaryl coenzyme A reductase inhibitors (statins) have anti-inflammatory
      and anti-apoptotic properties with few side effects, making it an attractive
      therapeutic option for prevention of CIN. A number of trials have examined the
      benefit of different types of statins, high-dose versus low-dose statins, loading
      versus chronic dosing of statins, in various clinical presentations including
      acute coronary syndromes and elective procedures, and in those with associated
      comorbidities such as anemia and chronic kidney disease. In this review, we will
      summarize recent data regarding statin therapy for prevention of contrast-induced
      nephropathy.

PMID- 25778427
TI  - Multicentric study on the diagnosis of Fabry's disease using angiokeratoma biopsy
      registries.

PMID- 25778428
TI  - Best practice guide for cryoballoon ablation in atrial fibrillation: The
      compilation experience of more than 3000 procedures.
AB  - BACKGROUND: Since the release of the second-generation cryoballoon (CB2; Arctic
      Front Advance(TM), Medtronic Inc) and its design modifications with improved
      cooling characteristics, the technique, dosing, and complication profile is
      significantly different from that of the first-generation cryoballoon. A
      comprehensive report of CB2 procedural recommendations has not been reported.
      OBJECTIVE: The purpose of this study was to review the current best practices
      from a group of experienced centers to create a user's consensus guide for CB2
      ablation. METHODS/RESULTS: High-volume operators with a combined experience of
      more than 3000 CB2 cases were interviewed, and consensus for technical and
      procedural best practice was established. CONCLUSION: Comprehensive review of the
      CB2 ablation best practice guide will provide a detailed technique for achieving
      safer and more effective outcomes for CB2 atrial fibrillation ablation.

PMID- 25778429
TI  - Cardiorespiratory fitness and atrial fibrillation: A population-based follow-up
      study.
AB  - BACKGROUND: Atrial fibrillation (AF) is the most common arrhythmia worldwide and
      has a complex association with physical fitness. The relationship of
      cardiorespiratory fitness (CRF) with the risk for AF has not been previously
      investigated in population-based studies. OBJECTIVE: The purpose of this study
      was to determine the relationship of CRF with incident AF. METHODS: CRF, as
      assessed by maximal oxygen uptake (VO2max) during exercise testing, was measured
      at baseline in 1950 middle-aged men (mean age 52.6 years, SD 5.1) from the Kuopio
      Ischaemic Heart Disease (KIHD) study. RESULTS: During average follow-up of 19.5
      years, there were 305 incident AF cases (annual AF rate of 65.1/1000 person
      years, 95% confidence interval [CI] 58.2-72.8). Overall, a nonlinear association
      was observed between CRF and incident AF. The rate of incident AF varied from
      11.5 (95% CI 9.4-14.0) for the first quartile of CRF, to 9.1 (95% CI 7.4-11.2)
      for the second quartile, 5.7 (95% CI 4.4-7.4) for the third quartile, and 6.3
      (95% CI 5.0-8.0) for the fourth quartile. Age-adjusted hazard ratio comparing top
      vs bottom fourth of usual CRF levels was 0.67 (95% CI 0.48-0.95), attenuated to
      0.98 (95% CI 0.66-1.43) upon further adjustment for risk factors. These findings
      were comparable across age, body mass index, history of smoking, diabetes, and
      cardiovascular disease status at baseline. CONCLUSION: Improved fitness as
      indicated by higher levels of CRF is protective of AF within a certain range,
      beyond which the risk of AF rises again. These findings warrant further
      replication.

PMID- 25778430
TI  - Endocardial (Watchman) vs epicardial (Lariat) left atrial appendage exclusion
      devices: Understanding the differences in the location and type of leaks and
      their clinical implications.
AB  - BACKGROUND: Watchman and Lariat left atrial appendage (LAA) occlusion devices are
      associated with LAA leaks postdeployment. OBJECTIVE: The purpose of this study
      was to compare the incidence, characteristics, and clinical significance of these
      leaks. METHODS: We performed a multicenter prospective observational study of all
      patients who underwent LAA closure. Baseline, procedural, and imaging variables
      along with LAA occlusion rates at 30-90 days and 1-year postprocedure were
      compared. RESULTS: A total of 478 patients (219 with the Watchman device and 259
      with the Lariat device) with successful implants were included. Patients in the
      Lariat group had a higher CHADS2 (congestive heart failure, hypertension, age >74
      years, diabetes, stroke) score and a larger left atrium and LAA. A total of 79
      patients (17%) had a detectable leak at 1 year. More patients in the Watchman
      group had a leak compared with those in the Lariat group (46 [21%] vs 33 [14%]; P
      = .019). All the leaks were eccentric (edge effect) in the Watchman group and
      concentric (gunny sack effect) in the Lariat group. The size of the leak was
      larger in the Watchman group than in the Lariat group (3.10 +/- 1.5 mm vs 2.15 +/
      1.3 mm; P = .001). The Watchman group had 1 device embolization requiring
      surgery and 2 pericardial effusions requiring pericardiocentesis. In the Lariat
      group, 4 patients had cardiac tamponade requiring urgent surgical repair. Three
      patients in each group had a cerebrovascular accident and were not associated
      with device leaks. CONCLUSION: The Lariat device is associated with a lower rate
      of leaks at 1 year as compared with the Watchman device, with no difference in
      rates of cerebrovascular accident. There was no correlation between the presence
      of residual leak and the occurrence of cerebrovascular accident.

PMID- 25778431
TI  - Preclinical testing and optimization of a novel fetal micropacemaker.

PMID- 25778432
TI  - Spinal cord stimulation protects against ventricular arrhythmias by suppressing
      left stellate ganglion neural activity in an acute myocardial infarction canine
      model.
AB  - BACKGROUND: Previous studies have shown that spinal cord stimulation (SCS) may
      reduce ventricular arrhythmias (VAs) induced by acute myocardial infarction
      (AMI). Furthermore, activation of left stellate ganglion (LSG) appears to
      facilitate VAs after AMI. OBJECTIVE: The purpose of this study was to investigate
      whether pretreatment with SCS could protect against VAs by reducing LSG neural
      activity in an AMI canine model. METHODS: Thirty dogs were anesthetized and
      randomly divided into SCS group (with SCS, n = 15) and sham group (sham operation
      without SCS, n = 15). SCS was performed for 1 hour before AMI. Heart rate
      variability (HRV), ventricular effective refractory period (ERP), serum
      norepinephrine level, LSG function measured by blood pressure increases in
      response to LSG stimulation, and LSG neural activity were measured for 1 minute
      at baseline and 1 hour after SCS. AMI was induced by left anterior descending
      coronary artery ligation, and then HRV, LSG neural activity, and VAs were
      measured. RESULTS: Compared to baseline, SCS for 1 hour significantly prolonged
      ventricular ERP, increased HRV, and attenuated LSG function and LSG activity in
      the SCS group, whereas no significant change was shown in the sham group. AMI
      resulted in a significant decrease in HRV and increase in LSG neural activity in
      the sham group, which were attenuated in the SCS group (frequency: 99 +/- 34
      impulses/min vs 62 +/- 22 impulses/min; amplitude: 0.41 +/- 0.12 mV vs 0.18 +/-
      0.05 mV; both P <.05). The incidence of VAs was significantly lower in the SCS
      group than in the sham group. CONCLUSION: SCS may prevent AMI-induced VAs,
      possibly by suppressing LSG activity.

PMID- 25778434
TI  - Nickel-catalyzed borylation of arenes and indoles via C-H bond cleavage.
AB  - The first nickel-catalyzed method for the borylation of carbon-hydrogen bonds in
      arenes and indoles is described. The use of an N-heterocyclic carbene ligand is
      essential for an efficient reaction, with an N-cyclohexyl-substituted derivative
      being optimal. This method is readily applied to the gram scale synthesis of 2
      borylindole. 

PMID- 25778433
TI  - Subcutaneous nerve activity is more accurate than heart rate variability in
      estimating cardiac sympathetic tone in ambulatory dogs with myocardial
      infarction.
AB  - BACKGROUND: We recently reported that subcutaneous nerve activity (SCNA) can be
      used to estimate sympathetic tone. OBJECTIVE: The purpose of this study was to
      test the hypothesis that left thoracic SCNA is more accurate than heart rate
      variability (HRV) in estimating cardiac sympathetic tone in ambulatory dogs with
      myocardial infarction (MI). METHODS: We used an implanted radiotransmitter to
      study left stellate ganglion nerve activity (SGNA), vagal nerve activity (VNA),
      and thoracic SCNA in 9 dogs at baseline and up to 8 weeks after MI. HRV was
      determined based on time-domain, frequency-domain, and nonlinear analyses.
      RESULTS: The correlation coefficients between integrated SGNA and SCNA averaged
      0.74 (95% confidence interval [CI] 0.41-1.06) at baseline and 0.82 (95% CI, 0.63
      1.01) after MI (P <.05 for both). The absolute values of the correlation
      coefficients were significantly larger than that between SGNA and HRV analysis
      based on time-domain, frequency-domain, and nonlinear analyses, respectively, at
      baseline (P <.05 for all) and after MI (P <.05 for all). There was a clear
      increment of SGNA and SCNA at 2, 4, 6, and 8 weeks after MI, whereas HRV
      parameters showed no significant changes. Significant circadian variations were
      noted in SCNA, SGNA, and all HRV parameters at baseline and after MI,
      respectively. Atrial tachycardia (AT) episodes were invariably preceded by SCNA
      and SGNA, which were progressively increased from 120th, 90th, 60th, to 30th
      seconds before AT onset. No such changes of HRV parameters were observed before
      AT onset. CONCLUSION: SCNA is more accurate than HRV in estimating cardiac
      sympathetic tone in ambulatory dogs with MI.

PMID- 25778435
TI  - Simvastatin exhibits antiproliferative effects on spheres derived from canine
      mammary carcinoma cells.
AB  - Mammary cancer is the most frequent type of tumor in the female canine.
      Treatments are mainly limited to surgery and chemotherapy; however, these tumors
      may develop clinical recurrence, metastasis and chemoresistance. The existence of
      a subpopulation of cancer cells with stemness features called cancer stem-like
      cells, may explain in part these characteristics of tumor progression. The
      statins, potent blockers of cholesterol synthesis, have also shown antitumor
      effects on cancer mammary cells, changes mediated by a decrease in the
      isoprenylation of specific proteins. Few studies have shown that simvastatin, a
      lipophilic statin, sensitizes cancer stem-like cells eliminating drug resistance.
      The aim of the present study was to evaluate the effects of simvastatin on
      spheres derived from CF41.Mg canine mammary tumor cells, which were characterized
      by phenotypic and functional analyses. Spheres exhibited characteristics of
      stemness, primarily expressing a CD44+/CD24-/low phenotype, displaying auto
      renewal and relative chemoresistance. Exposure to simvastatin induced a decrease
      in the sphere-forming capacity and cell viability, accompanied by a concentration
      and time-dependent increase in caspase-3/7 activity. In addition, modulation of
      beta-catenin and p53 expression was observed. Simvastatin triggered a synergistic
      effect with doxorubicin, sensitizing the spheres to the cytotoxic effect exerted
      by the drug. Invasiveness of spheres was decreased in response to simvastatin and
      this effect was counteracted by the presence of geranylgeranyl pyrophosphate. Our
      results suggest that simvastatin targets canine mammary cancer stem-like cells,
      supporting its therapeutical application as a novel agent to treat canine mammary
      cancer.

PMID- 25778446
TI  - Microwave-stimulated superconductivity due to presence of vortices.
AB  - The response of superconducting devices to electromagnetic radiation is a core
      concept implemented in diverse applications, ranging from the currently used
      voltage standard to single photon detectors in astronomy. Suprisingly, a
      sufficiently high power subgap radiation may stimulate superconductivity itself.
      The possibility of stimulating type II superconductors, in which the radiation
      may interact also with vortex cores, remains however unclear. Here we report on
      superconductivity enhanced by GHz radiation in type II superconducting Pb films
      in the presence of vortices. The stimulation effect is more clearly observed in
      the upper critical field and less pronounced in the critical temperature. The
      magnetic field dependence of the vortex related microwave losses in a film with
      periodic pinning reveals a reduced dissipation of mobile vortices in the
      stimulated regime due to a reduction of the core size. Results of numerical
      simulations support the validy of this conclusion. Our findings may have
      intriguing connections with holographic superconductors in which the possibility
      of stimulation is under current debate. 

PMID- 25778445
TI  - Effect of nebivolol on renal nitric oxide availability and tubular function in
      patients with essential hypertension.
AB  - AIMS: Nebivolol is a selective beta1 -receptor antagonist with vasodilating
      properties. In patients with essential hypertension, we tested the hypothesis
      that nebivolol increases systemic and renal nitric oxide (NO) availability using
      L-N(G) -monomethyl arginine (L-NMMA) as an inhibitor of NO production. METHODS:
      In a randomized, placebo-controlled, crossover study, patients with essential
      hypertension were treated with nebivolol for five days, along with a standardized
      diet and fluid intake. We examined the acute effects of systemic NO synthase
      inhibition with L-NMMA on brachial blood pressure (bBP), pulse wave velocity
      (PWV) and central blood pressure (cBP) estimated by applanation tonometry,
      glomerular filtration rate (GFR), fractional excretion of sodium (FENa ), urinary
      excretion of both aquaporin-2 (u-AQP2) and epithelial sodium channels (u
      ENaCgamma ), and plasma concentrations of nitrate/nitrite (p-NOx ) and vasoactive
      hormones after five days' treatment with placebo and nebivolol. RESULTS:
      Nebivolol significantly reduced PWV, bBP, cBP and plasma renin, angiotensin II
      and aldosterone concentrations. The renal parameters, p-NOx and plasma arginine
      vasopressin concentration were not changed by nebivolol. There was no difference
      between nebivolol and placebo in the response to L-NMMA, with LMMA inducing a
      similar increase in PWV, bBP and cBP and a similar decrease in GFR, uAQP2 and u
      ENaCgamma and FENa [mean change -0.62% (95% confidence interval {CI} -0.40 to 
      0.84) during placebo vs. -0.57% (95% CI -0.46 to -0.68; P = 0.564) during
      nebivolol treatment]. Vasoactive hormones were changed to a similar extend by L
      NMMA during administration of nebivolol and placebo. CONCLUSIONS: Nebivolol did
      not change p-NOx , and inhibition of NO synthesis induced the same response in
      blood pressure, GFR, renal tubular function and vasoactive hormones during
      nebivolol and placebo. Thus, the data did not support the hypothesis that
      nebivolol changes vascular and renal NO availability in patients with essential
      hypertension.

PMID- 25778447
TI  - Should HLA mismatch acceptability for sensitized transplant candidates be
      determined at the high-resolution rather than the antigen level?
AB  - Defining HLA mismatch acceptability of organ transplant donors for sensitized
      recipients has traditionally been based on serologically defined HLA antigens.
      Now, however, it is well accepted that HLA antibodies specifically recognize a
      wide range of epitopes present on HLA antigens and that molecularly defined high
      resolution alleles corresponding to the same low resolution antigen can possess
      different epitope repertoires. Hence, determination of HLA compatibility at the
      allele level represents a more accurate approach to identify suitable donors for
      sensitized patients. This approach would offer opportunities for increased
      transplant rates and improved long term graft survivals. 

PMID- 25778448
TI  - Solvent-induced synthesis of cobalt(II) coordination polymers based on a rigid
      ligand and flexible carboxylic acid ligands: syntheses, structures and magnetic
      properties.
AB  - Five new cobalt(ii) coordination architectures, {[Co(L)2(H2O)2].2H2O.2NO3}n (),
      {[Co(L)(ppda)].2H2O}n (), {[Co2(L)(ppda)2]2.H2O}n (), {[Co(L)(nba)].5H2O}n (),
      and {[Co(L)(oba)]2.3H2O}n (), have been constructed from the rigid ligand L [L =
      2,8-di(1H-imidazol-1-yl)dibenzofuran] and different flexible carboxylic acid
      ligands [H2ppda = 4,4'-(perfluoropropane-2,2-diyl)dibenzoic acid, H2nba = 4,4'
      azanediyldibenzoic acid, and H2oba = 4,4'-oxydibenzoic acid]. Depending on the
      nature of the solvent systems, these five different coordination polymers were
      synthesized and characterized by single-crystal X-ray diffraction, IR, PXRD and
      elemental analysis. Compounds , and were obtained by a one-pot method, and then
      we utilized the solvent-induced effect to obtain almost pure crystals of ,
      respectively. Compound is an infinite 1D chain which is formed by L ligands and
      Co atoms. Compound contains a [Co2(CO2)4] secondary building unit (SBU), and can
      be topologically represented as a 6-connected 2-fold interpenetrating pcu net
      with the point symbol of {4(12).6(3)}. Compound can be characterized as a 4
      connected sql tetragonal planar network with the point symbol of {4(4).6(2)}. In
      compounds and , there is a 1D chain which is formed by flexible carboxylic acid
      ligands and Co atoms; then the 1D chain is linked by L ligands in the tilting
      direction, leading to the formation of a 2D layer. Furthermore, UV-vis, TGA and
      magnetic properties have been investigated in detail. 

PMID- 25778449
TI  - Systems engineering meets quantitative systems pharmacology: from low-level
      targets to engaging the host defenses.
AB  - Quantitative systems pharmacology aims at systematizing, in a model-based manner,
      the integration of systems biology and pharmacology in an effort to rationalize
      the process of assessing the ability of a drug to enhance well-being by off
      setting the effects of a disease. Systems engineering, on the other hand, has
      enabled us to develop principles and methodologies for designing and operating
      engineered networks of structures exploring the integration of the underlying
      governing (design) laws. Although the computational tools which have resulted in
      major advances in the design, analysis, and operation of complex engineered
      structures have had tremendous success in the analysis of systems pharmacology
      models, it is argued in this opinion paper, that exploring the underlying
      conceptual foundation of complex systems engineering will enable us to move
      toward integrated models at the host level to explore, and possibly, induce
      synergies between low-level drug targets and higher level, systemic, defense
      mechanisms. This is an approach which would require refocusing of the key
      activities; however, it is likely the more promising approach as we enter the new
      era of personalized and precision medicine. We finally argue for the development
      of an allostatic approach to quantitative systems pharmacology and the
      development of an integrated framework for considering drugs in their broader
      context, beyond their local site of action. WIREs Syst Biol Med 2015, 7:101-112.
      doi: 10.1002/wsbm.1294 For further resources related to this article, please
      visit the WIREs website. CONFLICT OF INTEREST: The author has declared no
      conflicts of interest for this article.

PMID- 25778450
TI  - Plasma cell leukemia: from biology to treatment.
AB  - Plasma cell leukemia (PCL) is a very aggressive and rare form of malignant
      monoclonal gammopathy characterized by the presence of plasmocytes in peripheral
      blood. It is classified as primary PCL occuring 'de novo', or as secondary PCL in
      patients with relapsed/refractory multiple myeloma. Primary PCL is a distinct
      clinicopathological entity from myeloma with different cytogenetic abnormalities
      and molecular findings, which are usually found only in advanced multiple
      myeloma. The clinical course is aggressive with short remissions and reduced
      overall survival. The diagnostic criteria are based on the percentage (>20%) and
      absolute number (2 * 10(9) /L) of plasma cells in peripheral blood. After
      establishing diagnosis, induction therapy should begin promptly which is aimed to
      rapid disease control and to minimize the risk of early death. Intensive
      chemotherapy regimens and bortezomib-based regimens, followed by high-dose
      therapy with autologous stem cell transplantation, are recommended. Allogeneic
      transplantation can be considered in younger patients. This article reviews
      recent knowledge of this hematological malignancy that is associated with a very
      poor prognosis. 

PMID- 25778452
TI  - RNAi-mediated A disintegrin and metalloproteinase 9 gene silencing inhibits the
      tumor growth of non-small lung cancer in vitro and in vivo.
AB  - A disintegrin and metalloproteinase 9 (ADAM9) is a type I transmembrane protein
      that has been associated with cancer development and metastasis in various types
      of cancer. However, little is known about its role in non-small cell lung cancer
      (NSCLC). The aim of the present study was to evaluate whether downregulation of
      ADAM9 affects cell proliferation, apoptosis, migration and invasion in NSCLC.
      Thus, a recombinant lentiviral small hairpin RNA expression vector carrying ADAM9
      was constructed and infected into the human NSCLC cell line A549. Cell
      proliferation, apoptosis, migration and invasion in vitro and tumor growth in
      vivo were determined following downregulation of ADAM9 by RNA interference
      mediated ADAM9 gene silencing. It was found that downregulation of ADAM9
      expression using an RNA silencing approach in A549 tumor cells significantly
      inhibited cell proliferation, migration and invasion, induced cell apoptosis in
      vitro, as well as suppressed in vivo tumor growth in an experimental mouse model
      of lung metastasis. These data indicate that ADAM9 is potentially an important
      new therapeutic target for the prevention of tumor growth in NSCLC.

PMID- 25778453
TI  - Ultrafast dynamics of nanoplasmonic stopped-light lasing.
AB  - We study the spatio-temporal dynamics of coherent amplification and lasing in
      planar gain-enhanced nanoplasmonic structures and show that a singularity in the
      density of optical states leads to a stopped-light feedback mechanism that allows
      for cavity-free photonic and surface-plasmon polariton nanolasing. We reveal that
      in the absence of cavity-induced feedback a phase-locked superposition of a quasi
      dispersion-free waveguide mode promotes the dynamic formation of a subwavelength
      lasing mode. Simulations on the basis of a full-time domain Maxwell-Bloch
      Langevin approach uncover a high spontaneous emission factor beta~0.9 and
      demonstrate that the stopped-light lasing/spasing mechanism is remarkably robust
      against interface roughness. Stopped-light surface-plasmon polariton lasing is
      shown to be stable for gain sections of a width of down to 200 nm but in wider
      gain structures of the order of 1 MUm the dynamics is characterised by spatio
      temporally oscillating lasing surface-plasmon polaritons with typical temporal
      and spatial periods of smaller than 5 fs and smaller than 100 nm. Stopped-light
      lasing thus provides opportunities for ultrafast nanolasing and the realization
      of ultra-thin lasing surfaces and offers a new route to ultrafast spasing and
      cavity-free active quantum plasmonics.

PMID- 25778451
TI  - Biogeochemical insights into microbe-mineral-fluid interactions in hydrothermal
      chimneys using enrichment culture.
AB  - Active hydrothermal chimneys host diverse microbial communities exhibiting
      various metabolisms including those involved in various biogeochemical cycles. To
      investigate microbe-mineral-fluid interactions in hydrothermal chimney and the
      driver of microbial diversity, a cultural approach using a gas-lift bioreactor
      was chosen. An enrichment culture was performed using crushed active chimney
      sample as inoculum and diluted hydrothermal fluid from the same vent as culture
      medium. Daily sampling provided time-series access to active microbial diversity
      and medium composition. Active archaeal and bacterial communities consisted
      mainly of sulfur, sulfate and iron reducers and hydrogen oxidizers with the
      detection of Thermococcus, Archaeoglobus, Geoglobus, Sulfurimonas and Thermotoga
      sequences. The simultaneous presence of active Geoglobus sp. and Archaeoglobus
      sp. argues against competition for available carbon sources and electron donors
      between sulfate and iron reducers at high temperature. This approach allowed the
      cultivation of microbial populations that were under-represented in the initial
      environmental sample. The microbial communities are heterogeneously distributed
      within the gas-lift bioreactor; it is unlikely that bulk mineralogy or fluid
      chemistry is the drivers of microbial community structure. Instead, we propose
      that micro-environmental niche characteristics, created by the interaction
      between the mineral grains and the fluid chemistry, are the main drivers of
      microbial diversity in natural systems.

PMID- 25778454
TI  - Aldehyde dehydrogenase 2 polymorphism for development to hepatocellular carcinoma
      in East Asian alcoholic liver cirrhosis.
AB  - BACKGROUND AND AIM: We aimed to clarify the influences of aldehyde dehydrogenase
      2 (ALDH2), alcohol dehydrogenase 1B (ADH1B) polymorphisms, and ethanol
      consumption profile to hepatocellular carcinoma (HCC) development in alcoholic
      liver cirrhosis without chronic hepatitis B and C virus infection (non-B non-C).
      METHODS: Of 236 freshly diagnosed non-B non-C alcoholic liver cirrhosis patients,
      67 were diagnosed as HCC and the remaining 169 as not having HCC. The
      relationship between the genetic polymorphisms and development to HCC were
      evaluated in well-matched patients with HCC (HCC group, n = 67) and without HCC
      (non-HCC group, n = 67) using propensity scores in age, sex, and prevalence of
      diabetes mellitus. RESULTS: Daily amount of ethanol consumption was significantly
      lower (P = 0.005), and consumptive period was significantly longer (P = 0.003) in
      HCC group than non-HCC group. Of 134 well-matched patients, 113 (84.3%) had
      ALDH2*1/*1 genotype and 21 (15.7%) had ALDH2*1/*2 genotype. In HCC development,
      consumptive long period (P = 0.007) and carrying ALDH2*1/*2 genotype (P = 0.026)
      were identified as significant factors independently participated, while there
      was no relation to ADH1B polymorphism. In addition, consumptive period was
      significantly longer in HCC group than non-HCC group in ALDH2*1/*1 genotype
      patients (P = 0.0005), while there was no difference in profile of ethanol
      consumption in ALDH2*1/*2 genotype patients. Among HCC group, daily (P = 3.78 *
      10(-6) ) and cumulative amount (P = 4.89 * 10(-6) ) of ethanol consumption were
      significantly higher in ALDH2*1/*1 genotype patients than ALDH2*1/*2 genotype
      patients. CONCLUSION: In alcoholic liver cirrhosis, investigations of ALDH2
      polymorphism and ethanol consumption profile are useful for prediction of HCC
      development.

PMID- 25778455
TI  - Reversible logic gates based on enzyme-biocatalyzed reactions and realized in
      flow cells: a modular approach.
AB  - Reversible logic gates, such as the double Feynman gate, Toffoli gate and Peres
      gate, with 3-input/3-output channels are realized using reactions biocatalyzed
      with enzymes and performed in flow systems. The flow devices are constructed
      using a modular approach, where each flow cell is modified with one enzyme that
      biocatalyzes one chemical reaction. The multi-step processes mimicking the
      reversible logic gates are organized by combining the biocatalytic cells in
      different networks. This work emphasizes logical but not physical reversibility
      of the constructed systems. Their advantages and disadvantages are discussed and
      potential use in biosensing systems, rather than in computing devices, is
      suggested. 

PMID- 25778457
TI  - Symptom Manifestation and Impairments in College Students With ADHD.
AB  - To better understand the nature of impairment resulting from attention
      deficit/hyperactivity disorder (ADHD) for students in a post-secondary education
      (PSE) setting, the authors analyzed the symptoms and associated impairment of 135
      students with a diagnosis of ADHD who were recruited via Student Disability
      Services in Canadian post-secondary institutions. The authors (a) developed a
      novel semistructured telephone interview based on the 6-item Adult ADHD Self
      Report Scale Screener-Telephone Interview With Probes (ASRS-TIPS) to elicit
      students' descriptions of their behavior for each symptom they endorsed, (b)
      administered standardized tests of executive functioning (EF) and academic
      fluency, and (c) obtained self-reports of grade point averages (GPAs), EF,
      cognitive failures, psychopathology, distress, and resilience. Qualitative
      analysis of the ASRS-TIPS revealed significant impairment relating to symptoms of
      ADHD in the PSE setting. Students reported clinically significant symptoms of
      ADHD, psychological distress, and impairment in EF (67%, severe range) and
      cognitive failure (62%, atypical range) in everyday life. By contrast, their GPAs
      and standardized scores of EF and academic fluency were in the average range.
      Standardized scores and GPAs did not capture the impairment that participants
      experienced in their PSE settings. The ASRS-TIPS may provide a useful tool to
      help document how these students' symptoms impair functioning in the PSE setting.

PMID- 25778458
TI  - The Benefits of High School Career and Technical Education (CTE) for Youth With
      Learning Disabilities.
AB  - Using data from the National Longitudinal Transition Study-2 (NLTS2), this study
      examines the career and technical education (CTE) course taking of high school
      students with learning disabilities (LD) in the context of the national movement
      toward higher standards for determining whether students leave high school
      "college and career ready." Descriptive analyses document the extent of general
      education CTE course taking overall by students with LD and their engagement in a
      concentrated program of occupationally specific general education CTE, a level of
      course taking early research has linked to improved post-high school employment
      outcomes. Propensity score modeling was used to determine whether either type of
      CTE course taking is related to higher odds of full-time employment after high
      school and whether results differ with the length of time youth were out of high
      school. Results show no benefits of CTE course taking overall, but demonstrate a
      significant positive effect for participating in a concentration of
      occupationally specific CTE in the first 2 post-high school years; effects are
      nonsignificant for later years. The implications for high school programming and
      transition planning for students with LD are discussed.

PMID- 25778459
TI  - Special Issue Introduction: Adolescents and Young Adults With LD and/or ADHD
      Theoretical, Empirical, and Practical Perspectives.
AB  - The series of articles presented in this special issue focus on investigating two
      highly relevant objectives for adolescents and young adults with learning
      disabilities and/or attention-deficit/hyperactivity disorder: (a) examination of
      neuropsychological, educational, familial, and socioemotional features among
      individuals with these disabilities, in the adolescence and young adulthood
      developmental phases, and (b) exploration of specific dimensions of
      interventional programs and contextual (e.g., class) environments aiming to
      enhance these youngsters' academic achievements. Corresponding with these
      objectives, the six studies in this special issue provide new evidence regarding
      these two major topics, utilizing mixed qualitative and quantitative data
      analysis methods.

PMID- 25778456
TI  - Mood Disorders in Systemic Lupus Erythematosus: Results From an International
      Inception Cohort Study.
AB  - OBJECTIVE: To examine the frequency, characteristics, and outcome of mood
      disorders, as well as clinical and autoantibody associations, in a
      multiethnic/racial, prospective inception cohort of patients with systemic lupus
      erythematosus (SLE). METHODS: Patients were assessed annually for mood disorders
      (4 types, according to the Diagnostic and Statistical Manual of Mental Disorders,
      Fourth Edition) and 18 other neuropsychiatric events. Global disease activity
      scores (SLE Disease Activity Index 2000 [SLEDAI-2K]), damage scores (Systemic
      Lupus International Collaborating Clinics/American College of Rheumatology Damage
      Index [SDI]), and Short Form 36 subscales, mental and physical component summary
      scores were collected. Time to event, linear and ordinal regressions, and multi
      state models were used as appropriate. RESULTS: Among the 1,827 patients with
      SLE, 88.9% were female, and 48.9% were Caucasian. The mean +/- SD age of the
      patients was 35.1 +/- 13.3 years, disease duration was 5.6 +/- 4.8 months, and
      the length of followup was 4.7 +/- 3.5 years. During the course of the study, 863
      (47.2%) of the 1,827 patients had 1,627 neuropsychiatric events. Mood disorders
      occurred in 232 (12.7%) of 1,827 patients, and 98 (38.3%) of 256 mood disorder
      events were attributed to SLE. The estimated cumulative incidence of any mood
      disorder after 10 years was 17.7% (95% confidence interval 15.1, 20.2%). A
      greater risk of mood disorder was associated with concurrent neuropsychiatric
      events (P <= 0.01), and a lower risk was associated with Asian race/ethnicity (P
      = 0.01) and treatment with immunosuppressive drugs (P = 0.003). Mood disorders
      were associated with lower mental health and mental component summary scores but
      not with the SLEDAI-2K, SDI, or lupus autoantibodies. Among the 232 patients with
      depression, 168 (72.4%) were treated with antidepressants. One hundred twenty-six
      (49.2%) of 256 mood disorders resolved in 117 (50.4%) of 232 patients.
      CONCLUSION: Mood disorders, the second most frequent neuropsychiatric event in
      patients with SLE, have a negative impact on health-related quality of life and
      improve over time. The lack of association with global SLE disease activity,
      cumulative organ damage, and lupus autoantibodies emphasizes the multifactorial
      etiology of mood disorders and a role for non-lupus-specific therapies.

PMID- 25778460
TI  - N-acetylaspartate reduction in the medial prefrontal cortex following 8 weeks of
      risperidone treatment in first-episode drug-naive schizophrenia patients.
AB  - It is unclear whether N-acetylaspartate (NAA) depletions documented in
      schizophrenia patients might be due to the disease progression or medications.
      Here we investigated longitudinal NAA changes in drug-naive first-episode
      patients (FEP) who are relatively free from chronicity. Forty-two drug-naive FEP
      and 38 controls were enrolled in this study to explore the effect of 8-week
      risperidone monotherapy on NAA. All spectra were obtained from the medial
      prefrontal cortex (MPFC) on a 3.0 T MRI and analyzed with LCModel. At baseline,
      patients presented no significant differences in NAA (P = 0.084) or NAA/Cr + Pcr
      (P = 0.500) compared to controls; NAA levels were negatively correlated with
      PANSS total scores (P = 0.001) and WCST-PE (P = 0.041). After treatment, patients
      demonstrated significant reductions of NAA (P < 0.001) and NAA/Cr + Pcr (P <
      0.001), and significant improvement in PANSS-P (P < 0.001) and PANSS-G (P <
      0.001) symptoms. We detected no significant correlations between NAA alterations
      and PANSS-P (P = 0.679) or PANSS-G (P = 0.668) symptom changes; nor did NAA/Cr +
      Pcr changes with alterations in PANSS-P (P = 0.677) and PANSS-G (P = 0.616). This
      is the first evidence that short-term risperidone treatment induces an acute
      reduction of MPFC NAA during the early phase of schizophrenia, which may be a
      previously unavailable biomarker to indicate risperidone with a similar
      pharmacological mechanism, although the functional significance is still unclear.

PMID- 25778462
TI  - Genetic and structural analysis of polyomavirus BK T-antigens reveal a higher
      density of mutations at inter-domain and hexamerization regions, regardless the
      status of infection.
AB  - Polyomavirus BK (BKPyV) T-antigens (large and small tumor antigens, or Lt-ag and
      st-ag, respectively), control key aspects of viral replication and are able to
      regulate cell cycle, promoting cell proliferation. However, the structural
      effects of genetic mutations on T-antigens are poorly investigated. In this
      study, 214 sequences of T-antigens from individuals with different BKPyV
      infections (16 renal transplant with nephropathy; 78 asymptomatic renal
      transplant; 24 hematopoietic stem cell transplant with hemorrhagic cystitis; 96
      healthy non-transplant), were analyzed from the genetic and structural
      standpoints. We found a high concentration of non-synonymous mutations at inter
      domains and hexamerization regions of both proteins, being five of them under
      positive selection in the Lt-ag but none in the st-ag. The in silico analysis
      indicated that two mutations, located at positions 164 in the st-ag and 592 in
      the Lt-ag, would significantly affect the interaction with PP2A and p53 cell
      targets, respectively, although they were not associated to a specific clinical
      status. No mutations were detected on the J-domains or at the ATPase motif. In
      sum, the profile of the mutations found seem not to be associated to increased
      morbidity. This is the first work to analyze structural modifications on T
      antigens in different BKPyV infections, and managed to map conserved and variable
      regions of the T-antigens, which will be helpful for the study of new antiviral
      drugs.

PMID- 25778463
TI  - Quo vadis? Microbial profiling revealed strong effects of cleanroom maintenance
      and routes of contamination in indoor environments.
AB  - Space agencies maintain highly controlled cleanrooms to ensure the demands of
      planetary protection. To study potential effects of microbiome control, we
      analyzed microbial communities in two particulate-controlled cleanrooms (ISO 5
      and ISO 8) and two vicinal uncontrolled areas (office, changing room) by
      cultivation and 16S rRNA gene amplicon analysis (cloning, pyrotagsequencing, and
      PhyloChip G3 analysis). Maintenance procedures affected the microbiome on total
      abundance and microbial community structure concerning richness, diversity and
      relative abundance of certain taxa. Cleanroom areas were found to be mainly
      predominated by potentially human-associated bacteria; archaeal signatures were
      detected in every area. Results indicate that microorganisms were mainly spread
      from the changing room (68%) into the cleanrooms, potentially carried along with
      human activity. The numbers of colony forming units were reduced by up to ~400
      fold from the uncontrolled areas towards the ISO 5 cleanroom, accompanied with a
      reduction of the living portion of microorganisms from 45% (changing area) to 1%
      of total 16S rRNA gene signatures as revealed via propidium monoazide treatment
      of the samples. Our results demonstrate the strong effects of cleanroom
      maintenance on microbial communities in indoor environments and can be used to
      improve the design and operation of biologically controlled cleanrooms. 

PMID- 25778465
TI  - Effect of the CYP3A5 and ABCB1 genotype on exposure, clinical response and
      manifestation of toxicities from sunitinib in Asian patients.
AB  - The objective of this study was to determine the effect of the CYP3A5 and ATP
      binding cassette subfamily B member 1 (ABCB1) single-nucleotide polymorphisms on
      the disposition of sunitinib and SU12662, on clinical response, and on the
      manifestation of toxicities in Asian metastatic renal cell carcinoma patients. At
      week 4 of each treatment cycle, toxicities and plasma steady-state levels were
      assessed. Clinical response was assessed after two cycles. Genotyping was
      performed by using the PCR restriction fragment length polymorphism method. The
      CC genotype for ABCB1 was associated with a higher sunitinib exposure (76.81 vs
      56.55 ng ml(-1), P=0.03), higher risk of all-grade rash (RR 3.00, 95% CI 1.17
      7.67) and mucositis (RR 1.60, 95% CI 1.10-2.34) and disease progression than
      compared with the CT/TT genotype. There was a lack of association observed
      between the CYP3A5 polymorphism and exposure, response and toxicities. The
      polymorphism of ABCB1 (C3435T) has an important role in the manifestation of
      toxicities and drug exposure, but not polymorphism of CYP3A5. 

PMID- 25778466
TI  - A novel UGT1 marker associated with better tolerance against irinotecan-induced
      severe neutropenia in metastatic colorectal cancer patients.
AB  - The risk of severe irinotecan-induced neutropenia has been shown to be related to
      the UGT1 variant UGT1A1*28, which increases exposure to the potent metabolite SN
      38. Our goal was to identify a novel UGT1 marker(s) using 28 haplotype-tagged
      single nucleotide polymorphisms genotyped by mass spectrometry. By characterizing
      the UGT1 sequence from a cohort of 167 Canadian metastatic colorectal cancer
      (mCRC) patients and a validation cohort of 250 Italian mCRC patients, we found
      rs11563250G, located in the intergenic region downstream of UGT1, to be
      significantly associated with reduced risk of severe neutropenia (odds ratio
      (OR)=0.21; P=0.043 and OR=0.27; P=0.036, respectively, and OR=0.31 when combined;
      P=0.001), which remained significant upon correction for multiple testing in the
      combined cohort (P=0.041). For the two-marker haplotype rs11563250G and UGT1A1*1
      (rs8175347 TA6), the OR was of 0.17 (P=0.0004). Genetic testing of this marker
      may identify patients who might benefit from increased irinotecan dosing. 

PMID- 25778467
TI  - Genetic modifiers of response to glucose-insulin-potassium (GIK) infusion in
      acute coronary syndromes and associations with clinical outcomes in the IMMEDIATE
      trial.
AB  - Modifiers of response to glucose, insulin and potassium (GIK) infusion may affect
      clinical outcomes in acute coronary syndromes (ACS). In an Immediate Myocardial
      Metabolic Enhancement During Initial Assessment And Treatment In Emergency Care
      (IMMEDIATE) trial's sub-study (n = 318), we explored effects of 132,634 genetic
      variants on plasma glucose and potassium response to 12-h GIK infusion.
      Associations between metabolite-associated variants and infarct size (n = 84)
      were assessed. The 'G' allele of rs12641551, near ACSL1, as well as the 'A'
      allele of XPO4 rs2585897 were associated with a differential glucose response (P
      for 2 degrees of freedom test, P2df ? 4.75 * 10(-7)) and infarct size with GIK
      (P2df < 0.05). Variants within or near TAS1R3, LCA5, DNAH5, PTPRG, MAGI1, PTCSC3,
      STRADA, AKAP12, ARFGEF2, ADCYAP1, SETX, NDRG4 and ABCB11 modified glucose
      response, and near CSF1/AHCYL1 potassium response (P2df ? 4.26 * 10(-7)), but not
      outcomes. Gene variants may modify glucose and potassium response to GIK
      infusion, contributing to cardiovascular outcomes in ACS.

PMID- 25778468
TI  - Impact of genetic variants of RFC1, DHFR and MTHFR in osteosarcoma patients
      treated with high-dose methotrexate.
AB  - Osteosarcoma patients are commonly treated with high doses of methotrexate (MTX).
      MTX is an analog of folate, which is essential for DNA synthesis. Genetic
      polymorphism at single nucleotide can be indicative to the prognostic outcome in
      patients. Germ-line variants in candidate genes, coding for enzymes active in the
      metabolism of MTX, were studied in 62 osteosarcoma patients. Patients harboring
      the GG genotype in reduced folate carrier 1 (RFC1) rs1051266 had significantly
      better survival in comparison with patients having the AA genotype (P=0.046).
      These patients also had a lower frequency of metastasis (15%, P=0.029). Also
      patients homozygous for the G allele of rs1053129 in the dihydrofolate reductase
      (DHFR) gene were more likely to have a metastasis (45%, P= 0.005), and the
      methylenetetetrahydrofolate reductase (MTHFR) 677C allele was associated with
      higher degree of liver toxicity (88%, P=0.007). The study suggests that germ-line
      variants in the MTX metabolic pathway are associated with survival and side
      effects in patients treated with MTX.

PMID- 25778469
TI  - Genetic variants in DNA repair genes as potential predictive markers for
      oxaliplatin chemotherapy in colorectal cancer.
AB  - Oxaliplatin-based chemotherapy exerts its effects through generating DNA damage.
      Hence, genetic variants in DNA repair pathways could modulate treatment response.
      We used a prospective cohort of 623 colorectal cancer patients with stage II-IV
      disease treated with adjuvant/palliative chemotherapy to comprehensively
      investigate 1727 genetic variants in the DNA repair pathways as potential
      predictive markers for oxaliplatin treatment. Single nucleotide polymorphisms
      (SNP) associations with overall survival and recurrence-free survival were
      assessed using a Cox regression model. Pathway analysis was performed using the
      gamma method. Patients carrying variant alleles of rs3783819 (MNAT1) and
      rs1043953 (XPC) experienced a longer overall survival after treatment with
      oxaliplatin than patients who did not carry the variant allele, while the
      opposite association was found in patients who were not treated with oxaliplatin
      (false discovery rate-adjusted P-values for heterogeneity 0.0047 and 0.0237,
      respectively). The nucleotide excision repair (NER) pathway was found to be most
      likely associated with overall survival in patients who received oxaliplatin (P
      value=0.002). Our data show that genetic variants in the NER pathway are
      potentially predictive of treatment response to oxaliplatin. 

PMID- 25778470
TI  - Health Status and Psychological Distress in Patients with Non-compaction
      Cardiomyopathy: The Role of Burden Related to Symptoms and Genetic Vulnerability.
AB  - BACKGROUND: Non-compaction cardiomyopathy (NCCM) is a cardiomyopathy
      characterized by left ventricular tribeculae and deep intertrabecular recesses.
      Because of its genetic underpinnings and physical disease burden, noncompaction
      cardiomyopathy is expected to be associated with a lower health status and
      increase in pscyhological distress. PURPOSE: This study determined the health
      status and psychological distress in NCCM patients. We also examined the
      potential contribution of genetic predisposition and cardiac symptoms to health
      status and distress in NCCM, by comparing NCCM patients with (1) patients with
      familial hypercholesterolemia (FH) and (2) patients with acquired dilated
      cardiomyopathy (DCM). METHODS: Patients were recruited from the Erasmus Medical
      Center, Rotterdam, The Netherlands. Using a case-control design, NCCM patients (N
      = 45, mean age 46.7 +/- 15.1 years, 38 % male) were compared with 43 FH patients
      and 42 DCM patients. Outcome measures were health status (Short Form Health
      Survey-12), anxiety (Generalized Anxiety Disorder 7-item scale) and depression
      (Patient Health Questionnaire 9-item scale). RESULTS: NCCM patients showed
      significantly worse health status (Physical Component Score F(1,84) = 9.58, P =
      .003; Mental Component Score F(1,84) = 16.65, P < .001), anxiety (F(1,85) = 9.63,
      P = .003) and depression scores (F(1,82) = 5.4, P = .023) compared to FH
      patients, also after adjusting age, sex, comorbidity, educational level and time
      since diagnosis. However, NCCM patients did not differ from DCM patients
      (Physical Component Score F(1,82) = 2,61, P = .11; Mental Component Score F(1,82)
      = .55, P = .46), anxiety (F(1,82) = 1.16, P = .28) and depression scores (F(1,82)
      = 1,95, P = .17). CONCLUSION: Cardiac symptoms are likely to play a role in the
      observed poor health status and elevated levels of anxiety and depressive
      symptoms in NCCM, whereas the burden of having a genetic condition may contribute
      less to these health status and psychological measures.

PMID- 25778471
TI  - Is There a Connection Between Electrosensitivity and Electrosensibility? A
      Replication Study.
AB  - BACKGROUND: Among people with idiopathic environmental intolerance attributed to
      electromagnetic fields (IEI-EMF), a better than random detection ability for a 50
      Hz 0.5-mT magnetic field (MF) and a propensity to experience more symptoms than
      controls was reported in a previous study. PURPOSE: The current study aimed to
      replicate and clarify these results using a modified experimental design. METHOD:
      Participants of the provocation experiment were 49 individuals with self-reported
      IEI-EMF and 57 controls. They completed the questionnaires (symptom expectations,
      Somatosensory Amplification Scale--SSAS, radiation subscale of the Modern Health
      Worries Scale--MHWS Radiation) and attempted to detect the presence of the MF
      directed to their right arm in 20 subsequent 1-min sessions. Symptom reports were
      registered after each session. RESULTS: Individuals with IEI-EMF as opposed to
      the control group showed a higher than random detection performance (d' index of
      signal detection theory), while no difference in their bias (beta index) toward
      the presence of the MF was found. Predictors of reported symptoms were self
      reported IEI-EMF and believed as opposed to actual presence of the MF. People
      with IEI-EMF reported significantly more symptoms particularly in the believed
      presence of the MF. IEI-EMF was closely related to MHWS Radiation and SSAS
      scores. CONCLUSION: People with IEI-EMF might be able to detect the presence of
      the MF to a small extent; however, their symptom reports are connected to
      perceived exposure.

PMID- 25778472
TI  - Comparison of volumetric and linear serial CT assessments of lung metastases in
      renal cell carcinoma patients in a clinical phase IIB study.
AB  - RATIONALE AND OBJECTIVES: Accuracy of radiologic assessment may have a crucial
      impact on clinical studies and therapeutic decisions. We compared the variability
      of a central radiologic assessment (RECIST) and computer-aided volume-based
      assessment of lung lesions in patients with metastatic renal cell carcinoma
      (RCC). MATERIALS AND METHODS: The investigation was prospectively planned as a
      substudy of a clinical randomized phase IIB therapeutic trial in patients with
      RCC. Starting with the manual study diameter (SDM) of the central readers using
      RECIST in the clinical study, we performed computer-aided volume measurements. We
      compared SDM to an automated RECIST diameter (aRDM) and the diameter of a volume
      equivalent sphere (effective diameter [EDM]), both for the individual size
      measurements and for the change rate (CR) between consecutive time points. One
      hundred thirty diameter pairs of 30 lung lesions from 14 patients were evaluable,
      forming 55 change pairs over two consecutive time points each. RESULTS: The SDMs
      of two different readers showed a correlation of 95.6%, whereas the EDMs
      exhibited an excellent correlation of 99.4%. Evaluation of CRs showed an SDM-CR
      correlation of 63.9%, which is substantially weaker than the EDM-CR correlation
      of 87.6%. The variability of SDM-CR is characterized by a median absolute
      difference of 11.4% points versus the significantly lower 1.8% points EDM-CRs
      variability (aRDM: 3.2% points). The limits of agreement between readers suggest
      that an EDM change of 10% or 1 mm can already be significant. CONCLUSIONS:
      Computer-aided volume-based assessments result in markedly reduced variability of
      parameters describing size and change, which may offer an advantage of earlier
      response evaluations and treatment decisions for patients.

PMID- 25778473
TI  - Molecular psychiatry: 20 years.

PMID- 25778474
TI  - Multi-state outcome analysis of treatments (MOAT): application of a new approach
      to evaluate outcomes in longitudinal studies of bipolar disorder.
AB  - Survival analyzes are usually based on a single point in time predefined event.
      Dissatisfied with this approach to evaluating maintenance treatment outcomes, we
      developed the Multi-state Outcome Analysis of Treatments (MOAT) methodology using
      a combined database from two FDA registration studies of lamotrigine, lithium and
      placebo. MOAT partitions total survival time into clinically distinct periods
      operationally defined by cutpoints on rating scales. For bipolar disorder (BD),
      the clinical states are remission, subsyndromal and syndromal mania, mixed states
      or depression. MOAT results can be crossed with information about tolerability
      and functioning to yield an outcome system integrating efficacy and tolerability.
      As found in the original analysis, both drugs were associated with longer time in
      study compared with the placebo. MOAT supplements this by finding that both drugs
      increased the time remitted compared with placebo. However, a substantial amount
      of time in all three treatments was spent in subsyndromal depression. Time with
      manic symptoms was reduced with lithium, but not lamotrigine. Patients on placebo
      neither benefitted nor had adverse effects from the assignment but experienced
      more syndromal levels of symptoms and were terminated from the study sooner than
      either drug treated group. Lithium was associated with both benefit in time manic
      and worse tolerability compared with placebo. In summary, lamotrigine was
      associated with limited therapeutic benefit but not harm; lithium with both
      benefit and harm; and placebo with neither. MOAT describes not only quantity but
      also quality of time spent in longitudinal studies, providing a more clinically
      informative picture than Kaplan-Meier survival analysis. 

PMID- 25778475
TI  - Pathogenic mechanism of an autism-associated neuroligin mutation involves altered
      AMPA-receptor trafficking.
AB  - Neuroligins are postsynaptic cell-adhesion molecules that bind to presynaptic
      neurexins. Although the general synaptic role of neuroligins is undisputed, their
      specific functions at a synapse remain unclear, even controversial. Moreover,
      many neuroligin gene mutations were associated with autism, but the
      pathophysiological relevance of these mutations is often unknown, and their
      mechanisms of action uninvestigated. Here, we examine the synaptic effects of an
      autism-associated neuroligin-4 substitution (called R704C), which mutates a
      cytoplasmic arginine residue that is conserved in all neuroligins. We show that
      the R704C mutation, when introduced into neuroligin-3, enhances the interaction
      between neuroligin-3 and AMPA receptors, increases AMPA-receptor internalization
      and decreases postsynaptic AMPA-receptor levels. When introduced into neuroligin
      4, conversely, the R704C mutation unexpectedly elevated AMPA-receptor-mediated
      synaptic responses. These results suggest a general functional link between
      neuroligins and AMPA receptors, indicate that both neuroligin-3 and -4 act at
      excitatory synapses but perform surprisingly distinct functions, and demonstrate
      that the R704C mutation significantly impairs the normal function of neuroligin
      4, thereby validating its pathogenicity. 

PMID- 25778491
TI  - HMGB1-mediated autophagy modulates sensitivity of colorectal cancer cells to
      oxaliplatin via MEK/ERK signaling pathway.
AB  - In the present study, we examined the mechanisms of oxaliplatin-induced drug
      resistance in human colorectal cancer cell lines HT29 and HCT116. Our results
      demonstrate a significant autophagy expression in CRC cells after an oxaliplatin
      treatment. Administration of oxaliplatin to human CRC cells significantly
      enhanced the expression of HMGB1, which regulated the autophagy response and
      negatively regulate the cell apoptosis. Moreover, a decreased oxaliplatin 
      induced autophagy response and an increased apoptosis level were detected in
      stable CRC cells harboring HMGB1 shRNA. Then we noted that HMGB1 significantly
      induced extracellular signal-regulated kinase (ERK)/Extracellular signal
      regulated kinase kinase (MEK) phosphorylation. Taken together, these data suggest
      that HMGB1-mediated autophagy modulates sensitivity of colorectal cancer cells to
      oxaliplatin via MEK/ERK signaling pathway. 

PMID- 25778492
TI  - Genetic risk and age in Parkinson's disease: Continuum not stratum.
AB  - BACKGROUND: Recent genomewide association study meta-analyses have identified 28
      loci associated with risk of Parkinson's disease (PD). We sought to investigate
      whether these genetic risk factors are associated with PD age at onset. METHODS:
      Genetic risk scores from these loci were calculated for 6,249 cases. Linear
      regression tested associations between cumulative genetic risk and PD age at
      onset. RESULTS: Increasing genetic risk scores were associated with earlier age
      at onset (beta = -0.10, P = 2.92 * 10(-8) , adjusted r(2)  = 0.27). Single
      standard deviation increase in genetic risk score is associated with 37.44 d
      earlier age at onset. Highest genetic risk was found at 31 to 60 y, onset
      slightly below average age at onset (AAO). CONCLUSIONS: Common genetic risk
      factors have a small but consistent association with AAO in PD.

PMID- 25778493
TI  - Socioeconomic status moderates genetic and environmental effects on the amount of
      alcohol use.
AB  - BACKGROUND: Much is unknown about the relationship between socioeconomic status
      (SES) and alcohol use, including the means by which SES may influence risk for
      alcohol use. METHODS: Using a sample of 672 twin pairs (aged 25 to 74) derived
      from the MacArthur Foundation Survey of Midlife Development in the United States,
      this study examined whether SES, measured by household income and educational
      attainment, moderates genetic and environmental influences on 3 indices of
      alcohol use: amount used, frequency of use, and problem use. RESULTS: We found
      significant moderation for amount of alcohol used. Specifically, genetic effects
      were greater in low-SES conditions, shared environmental effects (i.e.,
      environmental effects that enhance the similarity of twins from the same
      families) tended to increase in high-SES conditions, and nonshared environmental
      effects (i.e., environmental effects that distinguish twins) tended to decrease
      with SES. This pattern of results was found for both income and education, and it
      largely replicated at a second wave of assessment spaced 9 years after the first.
      There was virtually no evidence of moderation for either frequency of alcohol use
      or alcohol problems. CONCLUSIONS: Our findings indicate that genetic and
      environmental influences on drinking amount vary as a function of the broader SES
      context, whereas the etiologies of other drinking phenomena are less affected by
      this context. Efforts to find the causes underlying the amount of alcohol used
      are likely to be more successful if such contextual information is taken into
      account.

PMID- 25778494
TI  - Peptide-DNA conjugates as tailored bivalent binders of the oncoprotein c-Jun.
AB  - We describe a ds-oligonucleotide-peptide conjugate that is able to efficiently
      dismount preformed DNA complexes of the bZIP regions of oncoproteins c-Fos and c
      Jun (AP-1), and therefore might be useful as disrupters of AP-1-mediated gene
      expression pathways. 

PMID- 25778495
TI  - Cannabis control policy: No rational basis yet for legalization.

PMID- 25778496
TI  - A Phase II Trial of Bexarotene for Advanced Differentiated Thyroid Cancer.

PMID- 25778497
TI  - Prevalence, course and determinants of carpal tunnel syndrome symptoms during
      pregnancy: a prospective study.
AB  - OBJECTIVE: To investigate the prevalence, severity and relation to fluid
      retention of self-reported pregnancy-related carpal tunnel syndrome (CTS)
      symptoms in a large sample of pregnant women. DESIGN: A prospective longitudinal
      cohort study. SETTING: Dutch women who became pregnant between January 2013 and
      January 2014 in the southeast of The Netherlands. POPULATION OR SAMPLE: A total
      of 639 Dutch pregnant women. METHODS: Baseline characteristics were assessed at
      12 weeks' gestation. CTS symptoms were assessed using the Boston Carpal Tunnel
      Questionnaire (BCTQ) at 32 weeks and during the first postpartum week regarding
      the last weeks of pregnancy. Fluid retention, sleeping problems and depressive
      symptoms (using the Edinburgh Depression Scale) were assessed at several time
      points during pregnancy. MAIN OUTCOME MEASURES: BCTQ scores, fluid retention and
      sleeping problems. RESULTS: Of the 639 women, 219 (34%) reported CTS symptoms
      during pregnancy. Total mean scores on the BCTQ were significantly higher after
      32 weeks' than up to 32 weeks' gestation. Most women experienced mild to moderate
      symptoms. Pregnant women with CTS symptoms reported significantly higher levels
      of fluid retention during gestation compared with pregnant women without CTS
      symptoms [F = 60.6, df (1598), P < 0.001], adjusted for body mass index (BMI),
      age, parity, and depression scores. Higher scores on fluid retention throughout
      the pregnancy were significantly related to CTS (OR = 1.8, 95%CI 1.5, 2.1, P <
      0.001). Finally, the occurrence of CTS was independently related to sleeping
      problems. CONCLUSIONS: Although the severity of symptoms and functional
      impairment of CTS were relatively mild, health care professionals should be aware
      of the high prevalence. The occurrence of CTS symptoms is significantly higher in
      women who report fluid retention during gestation and it can contribute to
      sleeping problems.

PMID- 25778498
TI  - Rationalising the geometric variation between the A and B monomers in the 1.9 A
      crystal structure of photosystem II.
AB  - Density functional theory calculations are reported on a set of models of the
      water-oxidising complex (WOC) of photosystem II (PSII), exploring structural
      features revealed in the most recent (1.9 A resolution) X-ray crystallographic
      studies of PSII. Crucially, we find that the variation in the Mn-Mn distances
      seen between the A and B monomers of this crystal structure can be entirely
      accounted for, in the low oxidation state (LOS) paradigm, by consideration of the
      interplay between two hydrogen-bonding interactions involving proximate amino
      acid residues with the oxo bridges of the WOC, that is, His337 with O3 (which
      leads to a general elongation in the Mn-Mn distances between Mn1, Mn2 and Mn3)
      and Arg357 with O2 (which results in a specific elongation of the Mn2-Mn3
      distance).

PMID- 25778499
TI  - Binge eating disorder and medical comorbidities in bariatric surgery candidates.
AB  - OBJECTIVE: To determine whether binge eating disorder (BED) status is associated
      with medical comorbidities in obese adults scheduled for bariatric surgery.
      METHOD: The study utilized Longitudinal Assessment of Bariatric Surgery-2 data
      obtained from six clinical centers around the United States. This is a well
      phenotyped cohort of individuals who were evaluated within 30 days before their
      scheduled surgery using standardized protocols. In the cohort, 350 participants
      were classified as having BED and 1,875 as not having BED (non-BED).
      Multivariable logistic regression was used to determine whether BED status was
      independently related to medical comorbidities. As an exploratory analysis,
      significance was based on nominal p-values (p < .05). Holm's-adjusted p-values
      were also reported. RESULTS: After adjusting for age, sex, education, and body
      mass index, BED status was found to be independently associated with four of the
      15 comorbidities (i.e., impaired glucose levels (odds ratio [OR] = 1.45 (95%
      confidence interval [CI]: 1.12-1.87)), high triglycerides (OR = 1.28 (95% CI:
      1.002-1.63)), and urinary incontinence (OR = 1.30 (95% CI: 1.02-1.66)), all being
      more common among the BED sample, and severe walking limitations being less
      common in the BED sample (OR = 0.53 (95% CI: 0.29-0.96)). With further adjustment
      for psychiatric/emotional health indicators, BED status was independently
      associated with three comorbidities (impaired glucose levels (OR = 1.36 (95% CI:
      1.04-1.79)), cardiovascular disease (OR = 0.50 (95% CI: 0.30-0.86)), and severe
      walking limitations (OR = 0.38 (95% CI: 0.19-0.77)). However, Holm's-adjusted p
      values for all variables were greater than .05. DISCUSSION: The results suggest
      the possibility of a contribution of BED to risk of specific medical
      comorbidities in severely obese adults.

PMID- 25778500
TI  - Diagnosis, Monitoring, and Treatment of Systemic Lupus Erythematosus: A
      Systematic Review of Clinical Practice Guidelines.
AB  - OBJECTIVE: Management of systemic lupus erythematosus (SLE) is complex and
      variability in practices exists. Guidelines have been developed to help improve
      the management of SLE patients, but there has been no formal evaluation of these
      guidelines. This study aims to compare the scope, quality, and consistency of
      clinical practice guidelines on the diagnosis, monitoring, and treatment of
      patients with SLE. METHODS: Electronic databases were searched up to April 2014.
      The Appraisal of Guidelines for Research and Evaluation (AGREE) II instrument and
      textual synthesis was used to appraise and compare recommendations. RESULTS: Nine
      clinical practice guidelines and 5 consensus statements were identified, which
      covered 7 topics: diagnosis, monitoring, treatment, neuropsychiatric SLE, lupus
      nephritis, antiphospholipid syndrome, and other manifestations of lupus. The
      methodological quality of the guidelines was variable, with the overall mean
      AGREE II scores ranging from 31% to 75%, out of a maximum 100%. Scores were
      consistently low for applicability, with only 1 guideline scoring above 50%.
      There was substantial variability in the treatments recommended for class II and
      V lupus nephritis, the recommended duration of maintenance therapy for class
      III/IV lupus nephritis (from 1 to 4 years), and timing of ophthalmologic
      examination for patients taking corticosteroids. CONCLUSION: Published guidelines
      on SLE cover a complex area of clinical care, but the methodological quality,
      scope, and recommendations varied substantially. Collaborative and
      multidisciplinary efforts to develop comprehensive, high-quality evidence-based
      guidelines are needed to promote best treatment and health outcomes for patients
      with SLE.

PMID- 25778502
TI  - Malaria control: tortoises and hares.

PMID- 25778501
TI  - Malaria transmission, infection, and disease at three sites with varied
      transmission intensity in Uganda: implications for malaria control.
AB  - The intensification of control interventions has led to marked reductions in
      malaria burden in some settings, but not others. To provide a comprehensive
      description of malaria epidemiology in Uganda, we conducted surveillance studies
      over 24 months in 100 houses randomly selected from each of three subcounties:
      Walukuba (peri-urban), Kihihi (rural), and Nagongera (rural). Annual
      entomological inoculation rate (aEIR) was estimated from monthly Centers for
      Disease Control and Prevention (CDC) light trap mosquito collections. Children
      aged 0.5-10 years were provided long-lasting insecticidal nets (LLINs) and
      followed for measures of parasite prevalence, anemia and malaria incidence.
      Estimates of aEIR were 2.8, 32.0, and 310 infectious bites per year, and
      estimates of parasite prevalence 7.4%, 9.3%, and 28.7% for Walukuba, Kihihi, and
      Nagongera, respectively. Over the 2-year study, malaria incidence per person
      years decreased in Walukuba (0.51 versus 0.31, P = 0.001) and increased in Kihihi
      (0.97 versus 1.93, P < 0.001) and Nagongera (2.33 versus 3.30, P < 0.001). Of
      2,582 episodes of malaria, only 8 (0.3%) met criteria for severe disease. The
      prevalence of anemia was low and not associated with transmission intensity. In
      our cohorts, where LLINs and prompt effective treatment were provided, the risk
      of complicated malaria and anemia was extremely low. However, malaria incidence
      was high and increased over time at the two rural sites, suggesting improved
      community-wide coverage of LLIN and additional malaria control interventions are
      needed in Uganda.

PMID- 25778503
TI  - Assessment of rectocolonic morphology and function in patients with Chagas
      disease in Barcelona (Spain).
AB  - The aim of this study was to determine the relationship between colonic symptoms,
      radiological abnormalities, and anorectal dysfunction in patients with Chagas
      disease. We performed a cross-sectional study of untreated patients diagnosed
      with Chagas disease. All patients were evaluated clinically (by a questionnaire
      for colonic symptoms based on Rome III criteria) and underwent a barium enema and
      anorectal manometry. A control group of patients with functional constipation and
      without Chagas disease was included in the study. Overall, 69 patients were
      included in the study: 42 patients were asymptomatic and 27 patients had
      abdominal symptoms according to Rome III criteria. Anorectal manometry showed a
      higher proportion of abnormalities in symptomatic patients than in asymptomatic
      ones (73% versus 21%, respectively; P < 0.0001). Megarectum was detected in a
      similar proportion in the different subgroups regardless of the presence of
      symptoms or abnormalities in anorectal functions. Among non-Chagas disease
      patients with functional constipation, 90% had an abnormal anorectal manometry
      study. Patients with Chagas disease present a high proportion of constipation
      with dyssynergic defecation in anorectal manometry but a low prevalence of
      impaired rectoanal inhibitory reflex, although these abnormalities may be
      nonspecific for Chagas disease. The presence of megarectum is a nonspecific
      finding.

PMID- 25778505
TI  - Trichomonas vaginalis Associated with Chronic Penile Ulcers and Multiple Urethral
      Fistulas.
AB  - The case of a 29-year-old, HIV-infected man presenting with Trichomonas vaginalis
      (TV)-associated chronic penile ulcers and multiple urethral fistulas is
      described. To our knowledge, this is the first description of chronic TV
      infection being implicated as the probable cause of a destructive lesion leading
      to sinus drainage and fistula formation. 

PMID- 25778504
TI  - Clinical and Epidemiological Characteristics of Scrub Typhus and Murine Typhus
      among Hospitalized Patients with Acute Undifferentiated Fever in Northern
      Vietnam.
AB  - A descriptive study on rickettsiosis was conducted at the largest referral
      hospital in Hanoi, Vietnam, to identify epidemiological and clinical
      characteristics of specific rickettsiosis. Between March 2001 and February 2003,
      we enrolled 579 patients with acute undifferentiated fever (AUF), excluding
      patients with malaria, dengue fever, and typhoid fever, and serologically tested
      for Orientia tsutsugamushi and Rickettsia typhi. Of the patients, 237 (40.9%) and
      193 (33.3%) had scrub and murine typhus, respectively, and 149 (25.7%) had
      neither of them (non-scrub and murine typhus [non-ST/MT]). The proportion of
      murine typhus was highest among patients living in Hanoi whereas that of scrub
      typhus was highest in national or regional border areas. The presence of an
      eschar, dyspnea, hypotension, and lymphadenopathy was significantly associated
      with a diagnosis of scrub typhus (OR = 46.56, 10.90, 9.01, and 7.92,
      respectively). Patients with murine typhus were less likely to have these
      findings but more likely to have myalgia, rash, and relative bradycardia (OR =
      1.60, 1.56, and 1.45, respectively). Scrub typhus and murine typhus were shown to
      be common causes of AUF in northern Vietnam although the occurrence of spotted
      fever group rickettsiae was not determined. Clinical and epidemiological
      information may help local clinicians make clinical diagnosis of specific
      rickettsioses in a resource-limited setting.

PMID- 25778506
TI  - Analysis of the pediatric health information system database as a surveillance
      tool for travel-associated infectious diseases.
AB  - The Pediatric Health Information System (PHIS) database collects admission,
      diagnostic, and treatment data among 44 children's hospitals across the United
      States (U.S.) and presents an opportunity for travel-associated infectious
      disease (TAID) surveillance. We calculated cumulative incidence rates among
      children admitted to 16 PHIS hospitals for dengue, malaria, and typhoid, and
      pooled TAID using discharge codes from 1999 to 2012. We compared incidence rates
      before, during, and after the 2007-2009 economic recession. Among 16 PHIS
      hospitals during the study period (1999-2012), incidence of dengue and pooled
      TAID (malaria, dengue, typhoid fever) increased significantly, and rates of
      malaria and typhoid trended upward. Admissions for dengue and pooled TAIDs
      increased significantly among 16 children's hospitals across the United States
      from 1999 to 2012. The PHIS database may provide a useful surveillance tool for
      TAIDs among children in the United States.

PMID- 25778476
TI  - A novel Alzheimer disease locus located near the gene encoding tau protein.
AB  - APOE E4, the most significant genetic risk factor for Alzheimer disease (AD), may
      mask effects of other loci. We re-analyzed genome-wide association study (GWAS)
      data from the International Genomics of Alzheimer's Project (IGAP) Consortium in
      APOE E4+ (10 352 cases and 9207 controls) and APOE E4- (7184 cases and 26 968
      controls) subgroups as well as in the total sample testing for interaction
      between a single-nucleotide polymorphism (SNP) and APOE E4 status. Suggestive
      associations (P<1 * 10(-4)) in stage 1 were evaluated in an independent sample
      (stage 2) containing 4203 subjects (APOE E4+: 1250 cases and 536 controls; APOE
      E4-: 718 cases and 1699 controls). Among APOE E4- subjects, novel genome-wide
      significant (GWS) association was observed with 17 SNPs (all between KANSL1 and
      LRRC37A on chromosome 17 near MAPT) in a meta-analysis of the stage 1 and stage 2
      data sets (best SNP, rs2732703, P=5.8 * 10(-9)). Conditional analysis revealed
      that rs2732703 accounted for association signals in the entire 100-kilobase
      region that includes MAPT. Except for previously identified AD loci showing
      stronger association in APOE E4+ subjects (CR1 and CLU) or APOE E4- subjects
      (MS4A6A/MS4A4A/MS4A6E), no other SNPs were significantly associated with AD in a
      specific APOE genotype subgroup. In addition, the finding in the stage 1 sample
      that AD risk is significantly influenced by the interaction of APOE with
      rs1595014 in TMEM106B (P=1.6 * 10(-7)) is noteworthy, because TMEM106B variants
      have previously been associated with risk of frontotemporal dementia. Expression
      quantitative trait locus analysis revealed that rs113986870, one of the GWS SNPs
      near rs2732703, is significantly associated with four KANSL1 probes that target
      transcription of the first translated exon and an untranslated exon in
      hippocampus (P ? 1.3 * 10(-8)), frontal cortex (P ? 1.3 * 10(-9)) and temporal
      cortex (P?1.2 * 10(-11)). Rs113986870 is also strongly associated with a MAPT
      probe that targets transcription of alternatively spliced exon 3 in frontal
      cortex (P=9.2 * 10(-6)) and temporal cortex (P=2.6 * 10(-6)). Our APOE-stratified
      GWAS is the first to show GWS association for AD with SNPs in the chromosome
      17q21.31 region. Replication of this finding in independent samples is needed to
      verify that SNPs in this region have significantly stronger effects on AD risk in
      persons lacking APOE E4 compared with persons carrying this allele, and if this
      is found to hold, further examination of this region and studies aimed at
      deciphering the mechanism(s) are warranted.

PMID- 25778507
TI  - Rotavirus seasonal distribution and prevalence before and after the introduction
      of rotavirus vaccine in a peri-urban community of Lima, Peru.
AB  - We evaluated the monthly distribution of rotavirus diarrhea in a cohort of
      children 12-24 months of age followed as part of a diarrhea clinical trial in a
      peri-urban community of Lima. We observed a peak of rotavirus diarrhea in the
      winter months and a decrease in rotavirus prevalence after the introduction of
      the rotavirus vaccine in Peru. 

PMID- 25778508
TI  - Early colonizers of unoccupied habitats represent a minority of the soil
      bacterial community.
AB  - In order to understand (re-)colonization of microhabitats and bacterial
      succession in soil, it is important to understand which members of soil bacterial
      communities are most motile in the porous soil matrix. To address this issue, we
      carried out a series of experiments in sterilized soil microcosms. Using two
      different model strains, Pseudomonas fluorescens strain Pf0-1 and Collimonas
      fungivorans strain Ter331, we first determined the influence of nutrient
      availability on bacterial expansion rates. Based on these results, we then
      conducted similar microcosm experiments to examine microbial mobility within
      natural soil bacterial communities under a single nutrient regime. The expansion
      of bacterial populations within the community was assayed by quantitative PCR and
      pyrosequencing of 16S rRNA gene fragments. We observed that only a relatively
      small subset of the total community was able to expand to an appreciable distance
      (more than 2 cm) within 48 h, with the genera Undibacterium, Pseudomonas and
      Massilia and especially the family Enterobacteriaceae dominating the communities
      more distant from the point of inoculation. These results suggest that (re
      )colonization of open habitats in soil may be dominated by a few rapidly moving
      species, which may have important consequences for microbial succession. 

PMID- 25778510
TI  - Diverse arsenic- and iron-cycling microbial communities in arsenic-contaminated
      aquifers used for drinking water in Bangladesh.
AB  - Subsurface removal of arsenic by injection with oxygenated groundwater has been
      proposed as a viable technology for obtaining 'safe' drinking water in
      Bangladesh. While the oxidation of ferrous iron to solid ferric iron minerals, to
      which arsenic adsorbs, is assumed to be driven by abiotic reactions, metal
      cycling microorganisms may potentially affect arsenic removal. A cultivation
      independent survey covering 24 drinking water wells in several geographical
      regions in Bangladesh was conducted to obtain information on microbial community
      structure and diversity in general, and on specific functional groups capable of
      the oxidation or reduction of arsenic or iron. Each functional group, targeted by
      either group-specific 16S rRNA or functional gene amplification, occurred in at
      least 79% of investigated samples. Putative arsenate reducers and iron-oxidizing
      Gallionellaceae were present at low diversity, while more variation in
      potentially arsenite-oxidizing microorganisms and iron-reducing
      Desulfuromonadales was revealed within and between samples. Relations between
      community composition on the one hand and hydrochemistry on the other hand were
      in general not evident, apart from an impact of salinity on iron-cycling
      microorganisms. Our data suggest widespread potential for a positive contribution
      of arsenite and iron oxidizers to arsenic removal upon injection with oxygenated
      water, but also indicate a potential risk for arsenic re-mobilization by
      anaerobic arsenate and iron reducers once injection is halted. 

PMID- 25778509
TI  - The carbon starvation response of the ectomycorrhizal fungus Paxillus involutus.
AB  - The amounts of carbon allocated to the fungal partner in ectomycorrhizal
      associations can vary substantially depending on the plant growth and the soil
      nutrient conditions, and the fungus may frequently be confronted with limitations
      in carbon. We used chemical analysis and transcriptome profiling to examine the
      physiological response of the ectomycorrhizal fungus Paxillus involutus to carbon
      starvation during axenic cultivation. Carbon starvation induced a decrease in the
      biomass. Concomitantly, ammonium, cell wall material (chitin) and proteolytic
      enzymes were released into the medium, which suggest autolysis. Compared with the
      transcriptome of actively growing hyphae, about 45% of the transcripts analyzed
      were differentially regulated during C-starvation. Induced during starvation were
      transcripts encoding extracellular enzymes such as peptidases, chitinases and
      laccases. In parallel, transcripts of N-transporters were upregulated, which
      suggest that some of the released nitrogen compounds were re-assimilated by the
      mycelium. The observed changes suggest that the carbon starvation response in P.
      involutus is associated with complex cellular changes that involves autolysis,
      recycling of intracellular compounds by autophagy and reabsorption of the
      extracellular released material. The study provides molecular markers that can be
      used to examine the role of autolysis for the turnover and survival of the
      ectomycorrhizal mycelium in soils. 

PMID- 25778527
TI  - Spatio-temporal patterns of leptospirosis in Thailand: is flooding a risk factor?
AB  - We studied the temporal and spatial patterns of leptospirosis, its association
      with flooding and animal census data in Thailand. Flood data from 2010 to 2012
      were extracted from spatial information taken from satellite images. The
      incidence rate ratio (IRR) was used to determine the relationship between spatio
      temporal flooding patterns and the number of human leptospirosis cases. In
      addition, the area of flood coverage, duration of waterlogging, time lags between
      flood events, and a number of potential animal reservoirs were considered in a
      sub-analysis. There was no significant temporal trend of leptospirosis over the
      study period. Statistical analysis showed an inconsistent relationship between
      IRR and flooding across years and regions. Spatially, leptospirosis occurred
      repeatedly and predominantly in northeastern Thailand. Our findings suggest that
      flooding is less influential in leptospirosis transmission than previously
      assumed. High incidence of the disease in the northeastern region is explained by
      the fact that agriculture and animal farming are important economic activities in
      this area. The periodic rise and fall of reported leptospirosis cases over time
      might be explained by seasonal exposure from rice farming activities performed
      during the rainy season when flood events often occur. We conclude that
      leptospirosis remains an occupational disease in Thailand. 

PMID- 25778528
TI  - How I treat hyperleukocytosis in acute myeloid leukemia.
AB  - Hyperleukocytosis (HL) per se is a laboratory abnormality, commonly defined by a
      white blood cell count >100,000/uL, caused by leukemic cell proliferation. Not
      the high blood count itself, but complications such as leukostasis, tumor lysis
      syndrome, and disseminated intravascular coagulation put the patient at risk and
      require therapeutic intervention. The risk of complications is higher in acute
      than in chronic leukemias, and particularly leukostasis occurs more often in
      acute myeloid leukemia (AML) for several reasons. Only a small proportion of AML
      patients present with HL, but these patients have a particularly dismal prognosis
      because of (1) a higher risk of early death resulting from HL complications; and
      (2) a higher probability of relapse and death in the long run. Whereas initial
      high blood counts and high lactate dehydrogenase as an indicator for high
      proliferation are part of prognostic scores guiding risk-adapted consolidation
      strategies, HL at initial diagnosis must be considered a hematologic emergency
      and requires rapid action of the admitting physician in order to prevent early
      death.

PMID- 25778530
TI  - Functions of idh1 and its mutation in the regulation of developmental
      hematopoiesis in zebrafish.
AB  - Isocitrate dehydrogenase 1 mutation (IDH1-R132H) was recently identified in acute
      myeloid leukemia with normal cytogenetics. The mutant enzyme is thought to
      convert alpha-ketoglutarate to the pathogenic 2-hydroxyglutarate (2-HG) that
      affects DNA methylation via inhibition of ten-eleven translocation 2. However,
      the role of wild-type IDH1 in normal hematopoiesis and its relevance to acute
      myeloid leukemia is unknown. Here we showed that zebrafish idh1 (zidh1) knockdown
      by morpholino and targeted mutagenesis by transcription activator-like effector
      nuclease might induce blockade in myeloid differentiation, as evident by an
      increase in pu.1 and decrease in mpo, l-plastin, and mpeg1 expression, and
      significantly reduce definitive hematopoiesis. Morpholino knockdown of zidh2 also
      induced a blockade in myeloid differentiation but definitive hematopoiesis was
      not affected. The hematopoietic phenotype of zidh1 knockdown was not rescuable by
      zidh2 messenger RNA, suggesting nonredundant functions. Overexpression of human
      IDH1-R132H or its zebrafish ortholog resulted in 2-HG elevation and expansion of
      myelopoiesis in zebrafish embryos. A human IDH1-R132H-specific inhibitor (AGI
      5198) significantly ameliorated both hematopoietic and 2-HG responses in human
      but not zebrafish IDH1 mutant expression. The results provided important insights
      to the role of zidh1 in myelopoiesis and definitive hematopoiesis and of IDH1
      R132H in leukemogenesis. 

PMID- 25778529
TI  - Enforced fucosylation of cord blood hematopoietic cells accelerates neutrophil
      and platelet engraftment after transplantation.
AB  - Delayed engraftment is a major limitation of cord blood transplantation (CBT),
      due in part to a defect in the cord blood (CB) cells' ability to home to the bone
      marrow. Because this defect appears related to low levels of fucosylation of cell
      surface molecules that are responsible for binding to P- and E-selectins
      constitutively expressed by the marrow microvasculature, and thus for marrow
      homing, we conducted a first-in-humans clinical trial to correct this deficiency.
      Patients with high-risk hematologic malignancies received myeloablative therapy
      followed by transplantation with 2 CB units, one of which was treated ex vivo for
      30 minutes with the enzyme fucosyltransferase-VI and guanosine diphosphate fucose
      to enhance the interaction of CD34(+) stem and early progenitor cells with
      microvessels. The results of enforced fucosylation for 22 patients enrolled in
      the trial were then compared with those for 31 historical controls who had
      undergone double unmanipulated CBT. The median time to neutrophil engraftment was
      17 days (range, 12-34 days) compared with 26 days (range, 11-48 days) for
      controls (P = .0023). Platelet engraftment was also improved: median was 35 days
      (range, 18-100 days) compared with 45 days (range, 27-120 days) for controls (P =
      .0520). These findings support ex vivo fucosylation of multipotent CD34(+) CB
      cells as a clinically feasible means to improve engraftment efficiency in the
      double CBT setting. The trial is registered to www.clinicaltrials.gov as
      #NCT01471067. 

PMID- 25778531
TI  - Merozoite surface protein 1 recognition of host glycophorin A mediates malaria
      parasite invasion of red blood cells.
AB  - Plasmodium falciparum invasion of human red blood cells (RBCs) is an intricate
      process requiring a number of distinct ligand-receptor interactions at the
      merozoite-erythrocyte interface. Merozoite surface protein 1 (MSP1), a highly
      abundant ligand coating the merozoite surface in all species of malaria
      parasites, is essential for RBC invasion and considered a leading candidate for
      inclusion in a multiple-subunit vaccine against malaria. Our previous studies
      identified an interaction between the carboxyl-terminus of MSP1 and RBC band 3.
      Here, by employing phage display technology, we report a novel interaction
      between the amino-terminus of MSP1 and RBC glycophorin A (GPA). Mapping of the
      binding domains established a direct interaction between malaria MSP1 and human
      GPA within a region of MSP1 known to potently inhibit P falciparum invasion of
      human RBCs. Furthermore, a genetically modified mouse model lacking the GPA- band
      3 complex in RBCs is completely resistant to malaria infection in vivo. These
      findings suggest an essential role of the MSP1-GPA-band 3 complex during the
      initial adhesion phase of malaria parasite invasion of RBCs. 

PMID- 25778532
TI  - Macrophages and iron trafficking at the birth and death of red cells.
AB  - Macrophages play a critical role in iron homeostasis via their intimate
      association with developing and dying red cells. Central nurse macrophages
      promote erythropoiesis in the erythroblastic island niche. These macrophages make
      physical contact with erythroblasts, enabling signaling and the transfer of
      growth factors and possibly nutrients to the cells in their care. Human mature
      red cells have a lifespan of 120 days before they become senescent and again come
      into contact with macrophages. Phagocytosis of red blood cells is the main source
      of iron flux in the body, because heme must be recycled from approximately 270
      billion hemoglobin molecules in each red cell, and roughly 2 million senescent
      red cells are recycled each second. Here we will review pathways for iron
      trafficking found at the macrophage-erythroid axis, with a focus on possible
      roles for the transport of heme in toto. 

PMID- 25778534
TI  - Stromal cell-mediated glycolytic switch in CLL cells involves Notch-c-Myc
      signaling.
AB  - It is well established that the stromal niche exerts a protective effect on
      chronic lymphocytic leukemia (CLL) cells, thereby also affecting their drug
      sensitivity. One hallmark of malignant cells is metabolic reprogramming, which is
      mostly represented by a glycolytic shift known as the Warburg effect. Because
      treatment resistance can be linked to metabolic alterations, we investigated
      whether bone marrow stromal cells impact the bioenergetics of primary CLL cells.
      In fact, stromal contact led to an increase of aerobic glycolysis and the cells'
      overall glycolytic capacity accompanied by an increased glucose uptake,
      expression of glucose transporter, and glycolytic enzymes. Activation of Notch
      signaling and of its direct transcriptional target c-Myc contributed to this
      metabolic switch. Based on these observations, CLL cells' acquired increased
      glucose dependency as well as Notch-c-Myc signaling could be therapeutically
      exploited in an effort to overcome stroma-mediated drug resistance. 

PMID- 25778533
TI  - BET bromodomain inhibition suppresses graft-versus-host disease after allogeneic
      bone marrow transplantation in mice.
AB  - Acute graft-versus-host disease (GVHD) is the major obstacle of allogeneic bone
      marrow transplantation (BMT). Bromodomain and extra-terminal (BET) protein
      inhibitors selectively block acetyl-binding pockets of the bromodomains and
      modulate histone acetylation. Here, we report that inhibition of BET bromodomain
      (BRD) proteins with I-BET151 alters cytokine expression in dendritic cells (DCs)
      and T cells, including surface costimulatory molecules, in vitro and in vivo
      cytokine secretion, and expansion. Mechanistic studies with I-BET151 and JQ1,
      another inhibitor, demonstrate that these effects could be from disruption of
      association between BRD4 and acetyl-310 RelA of nuclear factor kappa B. Short
      term administration early during BMT reduced GVHD severity and improved mortality
      in two different allogeneic BMT models but retained sufficient graft-versus-tumor
      effect. Thus inhibiting BRD proteins may serve as a novel approach for preventing
      GVHD. 

PMID- 25778535
TI  - ICL-induced miR139-3p and miR199a-3p have opposite roles in hematopoietic cell
      expansion and leukemic transformation.
AB  - Interstrand crosslinks (ICLs) are toxic DNA lesions that cause severe genomic
      damage during replication, especially in Fanconi anemia pathway-deficient cells.
      This results in progressive bone marrow failure and predisposes to acute myeloid
      leukemia (AML). The molecular mechanisms responsible for these defects are
      largely unknown. Using Ercc1-deficient mice, we show that Trp53 is responsible
      for ICL-induced bone marrow failure and that loss of Trp53 is leukemogenic in
      this model. In addition, Ercc1-deficient myeloid progenitors gain elevated levels
      of miR-139-3p and miR-199a-3p with age. These microRNAs exert opposite effects on
      hematopoiesis. Ectopic expression of miR-139-3p strongly inhibited proliferation
      of myeloid progenitors, whereas inhibition of miR-139-3p activity restored
      defective proliferation of Ercc1-deficient progenitors. Conversely, the
      inhibition of miR-199a-3p functions aggravated the myeloid proliferation defect
      in the Ercc1-deficient model, whereas its enforced expression enhanced
      proliferation of progenitors. Importantly, miR-199a-3p caused AML in a pre
      leukemic mouse model, supporting its role as an onco-microRNA. Target genes
      include HuR for miR-139-3p and Prdx6, Runx1, and Suz12 for miR-199a-3p. The
      latter genes have previously been implicated as tumor suppressors in de novo and
      secondary AML. These findings show that, in addition to TRP53-controlled
      mechanisms, miR-139-3p and miR-199a-3p are involved in the defective
      hematopoietic function of ICL-repair deficient myeloid progenitors. 

PMID- 25778536
TI  - Systematic content evaluation and review of measurement properties of
      questionnaires for measuring self-reported fatigue among older people.
AB  - PURPOSE: The assessment of fatigue in older people requires simple and user
      friendly questionnaires that capture the phenomenon, yet are free from items
      indistinguishable from other disorders and experiences. This study aimed to
      evaluate the content, and systematically review and rate the measurement
      properties of self-report questionnaires for measuring fatigue, in order to
      identify the most suitable questionnaires for older people. METHODS: This study
      firstly involved identification of questionnaires that purport to measure self
      reported fatigue, and evaluation of the content using a rating scale developed
      for the purpose from contemporary understanding of the construct. Secondly, for
      the questionnaires that had acceptable content, we identified studies reporting
      measurement properties and rated the methodological quality of those studies
      according to the COSMIN system. Finally, we extracted and synthesised the results
      of the studies to give an overall rating for each questionnaire for each
      measurement property. The protocol was registered with PROSPERO (CRD42013005589).
      RESULTS: Of the 77 identified questionnaires, twelve were selected for review
      after content evaluation. Methodological quality varied, and there was a lack of
      information on measurement error and responsiveness. CONCLUSIONS: The PROMIS
      Fatigue item bank and short forms perform the best. The FACIT-Fatigue scale,
      Parkinsons Fatigue Scale, Perform Questionnaire, and Uni-dimensional Fatigue
      Impact Scale also perform well and can be recommended. Minor modifications to
      improve performance are suggested. Further evaluation of unresolved measurement
      properties, particularly with samples including older people, is needed for all
      the recommended questionnaires.

PMID- 25778537
TI  - Predicting Outcome of Community-Based Early Intensive Behavioral Intervention for
      Children with Autism.
AB  - We examined predictors of outcome (IQ, adaptive behavior, and ASD severity) after
      12 and 24 months of early intensive behavioral intervention (EIBI) in 71, 20-59
      months old children with autism spectrum disorder (ASD) who were enrolled in
      publicly-funded, community-based agencies. Predictors included social engagement
      (combining variables loading onto a single factor: social approach, joint
      attention, and imitation) and sensorimotor rituals. Younger age and higher IQ at
      intake predicted favorable outcomes at both 12 and 24 months. Adjusting for age,
      IQ, baseline predictor scores, EIBI hours, treatment site, and sensorimotor
      rituals, social engagement predicted superior later IQ and adaptive behavior. In
      contrast, sensorimotor rituals did not predict outcome. Although limited by the
      absence of a control group, the study indicates social engagement predicts some
      EIBI outcomes. 

PMID- 25778538
TI  - Med1 regulates meiotic progression during spermatogenesis in mice.
AB  - Spermatogenesis is a highly coordinated process. Signaling from nuclear hormone
      receptors, like those for retinoic acid (RA), is important for normal
      spermatogenesis. However, the mechanisms regulating these signals are poorly
      understood. Mediator complex subunit 1 (MED1) is a transcriptional enhancer that
      directly modulates transcription from nuclear hormone receptors. MED1 is present
      in male germ cells throughout mammalian development, but its function during
      spermatogenesis is unknown. To determine its role, we generated mice lacking Med1
      specifically in their germ cells beginning just before birth. Conditional Med1
      knockout males are fertile, exhibiting normal testis weights and siring ordinary
      numbers of offspring. RA-responsive gene products stimulated by RA gene 8 (Stra8)
      and synaptonemal complex protein 3 (Sycp3) are first detected in knockout
      spermatogonia at the expected time points during the first wave of
      spermatogenesis, and persist with normal patterns of cellular distribution in
      adult knockout testes. Meiotic progression, however, is altered in the absence of
      Med1. At postnatal day 7 (P7), zygotene-stage knockout spermatocytes are already
      detected, unlike in control testes, with fewer pre-leptotene-stage cells and more
      leptotene spermatocytes observed in the knockouts. At P9, Med1 knockout
      spermatocytes prematurely enter pachynema. Once formed, greater numbers of
      knockout spermatocytes remain in pachynema relative to the other stages of
      meiosis throughout testis development and its maintenance in the adult. Meiotic
      exit is not inhibited. We conclude that MED1 regulates the temporal progression
      of primary spermatocytes through meiosis, with its absence resulting in
      abbreviated pre-leptotene, leptotene, and zygotene stages, and a prolonged
      pachytene stage. 

PMID- 25778539
TI  - Neonatal exposure to xenoestrogens impairs the ovarian response to gonadotropin
      treatment in lambs.
AB  - Bisphenol A (BPA) and diethylstilbestrol (DES) are xenoestrogens, which have been
      associated with altered effects on reproduction. We hypothesized that neonatal
      xenoestrogen exposure affects the ovarian functionality in lambs. Thus, we
      evaluated the ovarian response to exogenous ovine FSH (oFSH) administered from
      postnatal day 30 (PND30) to PND32 in female lambs previously exposed to low doses
      of DES or BPA (BPA50: 50 MUg/kg per day, BPA0.5: 0.5 MUg/kg per day) from PND1 to
      PND14. We determined: i) follicular growth, ii) circulating levels of 17beta
      estradiol (E2), iii) steroid receptors (estrogen receptor alpha, estrogen
      receptor beta, and androgen receptor (AR)) and atresia, and iv) mRNA expression
      levels of the ovarian bone morphogenetic protein (BMPs) system (BMP6, BMP15,
      BMPR1B, and GDF9) and FSH receptor (FSHR). Lambs neonatally exposed to DES or BPA
      showed an impaired ovarian response to oFSH with a lower number of follicles >=2
      mm in diameter together with a lower number of atretic follicles and no increase
      in E2 serum levels in response to oFSH treatment. In addition, AR induction by
      oFSH was disrupted in granulosa and theca cells of lambs exposed to DES or BPA.
      An increase in GDF9 mRNA expression levels was observed in oFSH-primed lambs
      previously treated with DES or BPA50. In contrast, a decrease in BMPR1B was
      observed in BPA0.5-postnatally exposed lambs. The modifications in AR, GDF9, and
      BMPR1B may be associated with the altered ovarian function due to neonatal
      xenoestrogen exposure in response to an exogenous gonadotropin stimulus. These
      alterations may be the pathophysiological basis of subfertility syndrome in
      adulthood. 

PMID- 25778540
TI  - Heparinized nanohydroxyapatite/collagen granules for controlled release of
      vancomycin.
AB  - The purpose of this study was to develop a bone substitute material capable of
      preventing or treating osteomyelitis through a sustainable release of vancomycin
      and simultaneously inducing bone regeneration. Porous heparinized
      nanohydroxyapatite (nanoHA)/collagen granules were characterized using scanning
      electron microscopy, micro-computed tomography and attenuated total reflectance
      Fourier transform infrared spectroscopy. After vancomycin adsorption onto the
      granules, its releasing profile was studied by UV molecular absorption
      spectroscopy. The heparinized granules presented a more sustainable release over
      time, in comparison with nonheparinized nanoHA and nanoHA/collagen granules.
      Vancomycin was released for 360 h and proved to be bioactive until 216 h.
      Staphylococcus aureus adhesion was higher on granules containing collagen,
      guiding the bacteria to the material with antibiotic, improving their
      eradication. Moreover, cytotoxicity of the released vancomycin was assessed using
      osteoblast cultures, and after 14 days of culture in the presence of vancomycin,
      cells were able to remain viable, increasing their metabolic activity and
      colonizing the granules, as observed by scanning electron microscopy and confocal
      laser scanning microscopy. These findings suggest that heparinized
      nanoHA/collagen granules are a promising material to improve the treatment of
      osteomyelitis, as they are capable of releasing vancomycin, eliminating the
      bacteria, and presented morphological and chemical characteristics to induce bone
      regeneration.

PMID- 25778541
TI  - Uptake and bioavailability of anthocyanins and phenolic acids from
      grape/blueberry juice and smoothie in vitro and in vivo.
AB  - The goal of eating five servings of fruits and vegetables a day has not yet been
      achieved. The intake of polyphenols such as anthocyanins (ACN) could be improved
      by consuming smoothies and juices that are increasingly popular, especially in
      children; however, bioavailability data concerning food matrix effects are
      scarce. Thus, we conducted a randomised, cross-over, bioavailability study (n 10)
      to determine the bioavailability of ACN and their metabolites from an ACN-rich
      grape/blueberry juice (841 mg ACN/litre) and smoothie (983 mg ACN/litre) in vivo,
      and the uptake of a corresponding grape/blueberry extract in vitro. After the
      intake of beverage (0.33 litres), plasma and fractionated urine samples were
      collected and analysed by ultra-performance liquid chromatography coupled to MS.
      The most abundant ACN found in plasma and urine were malvidin and peonidin as
      native ACN and as glucuronidated metabolites as well as 3,4-dihydroxybenzoic acid
      (3,4-DHB); minor ACN (delphinidin, cyanidin and petunidin) were only detected as
      native glycosides. Plasma pharmacokinetics and recoveries of urinary metabolites
      of ACN were not different for juice or smoothie intake; however, the phenolic
      acid 3,4-DHB was significantly better bioavailable from juice in comparison to
      smoothie. In vitro data with absorptive intestinal cells indicated that despite
      their weak chemical stability, ACN and 3,4-DHB could be detected at the basal
      side in their native forms. Whether smoothies as well as juices should be
      recommended to increase the intake of potentially health-promoting ACN and other
      polyphenols requires the consideration of other ingredients such as their
      relatively high sugar content. 

PMID- 25778542
TI  - Direct parasagittal magnetic resonance imaging of the internal auditory canal to
      determine cochlear or auditory brainstem implant candidacy in children.

PMID- 25778543
TI  - A new bovine conjunctiva model shows that Listeria monocytogenes invasion is
      associated with lysozyme resistance.
AB  - Listerial keratoconjunctivitis ('silage eye') is a wide spread problem in
      ruminants causing economic losses to farmers and impacts negatively on animal
      welfare. It results from direct entry of Listeria monocytogenes into the eye,
      often following consumption of contaminated silage. An isolation protocol for
      bovine conjunctival swabbing was developed and used to sample both infected and
      healthy eyes bovine eyes (n=46). L. monocytogenes was only isolated from one
      healthy eye sample, and suggests that this organism can be present without
      causing disease. To initiate a study of this disease, an infection model was
      developed using isolated conjunctiva explants obtained from cattle eyes post
      slaughter. Conjunctiva were cultured and infected for 20 h with a range of L.
      monocytogenes isolates (n=11), including the healthy bovine eye isolate and also
      strains isolated from other bovine sources, such as milk or clinical infections.
      Two L. monocytogenes isolates (one from a healthy eye and one from a cattle
      abortion) were markedly less able to invade conjunctiva explants, but one of
      those was able to efficiently infect Caco2 cells indicating that it was fully
      virulent. These two isolates were also significantly more sensitive to lysozyme
      compared to most other isolates tested, suggesting that lysozyme resistance is an
      important factor when infecting bovine conjunctiva. In conclusion, we present the
      first bovine conjunctiva explant model for infection studies and demonstrate that
      clinical L. monocytogenes isolates from cases of bovine keratoconjunctivitis are
      able to infect these tissues.

PMID- 25778544
TI  - Influenza A(H1N1)pdm09 virus in pigs, Togo, 2013.
AB  - We collected 325 nasal swabs from freshly slaughtered previously healthy pigs
      from October 2012 through January 2014 in a slaughterhouse near Lome in Togo.
      Influenza A virus genome was detected by RT-PCR in 2.5-12.3% of the pooled
      samples, and results of hemagglutinin subtyping RT-PCR assays showed the virus in
      all the positive pools to be A(H1N1)pdm09. Virus was isolated on MDCK cells from
      a representative specimen, A/swine/Togo/ONA32/2013(H1N1). The isolate was fully
      sequenced and harbored eight genes similar to A(H1N1)pdm09 virus genes
      circulating in humans in 2012-2013, suggesting human-to-swine transmission of the
      pathogen. 

PMID- 25778545
TI  - Seroprevalence of Coxiella burnetii in domesticated and feral cats in eastern
      Australia.
AB  - The seroprevalence of Coxiella burnetii (C. burnetii) in cats in eastern
      Australia is unknown, and the risk of transmission from cats to humans is
      undetermined. This study aimed to determine the exposure of cats to C. burnetii
      in four distinct cat subpopulations. An indirect immunofluoresence assay (IFA)
      and an Enzyme-linked immunosorbent assay (ELISA) used for detection of anti-C.
      burnetii antibodies in humans were adapted, verified for use on feline serum, and
      compared. Cat serum samples (n=712) were tested with IFA from four subpopulations
      [cattery-confined breeding cats, pet cats, feral cats and shelter cats]. The
      proportions of seropositive cats were; cattery-confined breeding cats (35/376,
      9.3%), pets (2/198, 1%), feral cats (0/50), shelter cats (0/88). The significant
      variables in C. burnetii seropositivity were cattery-confined breeding cat
      subpopulation and sterilisation status, with infected cats 17.1 (CI 4.2-70.2;
      P<0.001) times more likely to be cattery-confined breeding cats and 6.00 (CI 2.13
      16.89; P<0.001) times more likely to be entire than sterilised. ELISA was used on
      143 of 712 sera tested with IFA, and the Cohen's Kappa coefficient of 0.75
      indicated 92.2% agreement between the two assays. These results confirm that
      Australian cats have been exposed to C. burnetii and that a higher seroprevalence
      of C. burnetii is seen amongst cattery-confined breeding cats. Cat breeders and
      veterinary personnel involved in feline reproductive procedures may be at higher
      risk of exposure to C. burnetii. 

PMID- 25778546
TI  - Prevalence of the immune evasion gene cluster in Staphylococcus aureus CC398.
AB  - The immune evasion gene cluster (IEC) is typical for Staphylococcus aureus
      isolated from humans but is usually absent in S. aureus isolated from animals.
      Previous studies have shown that methicillin resistant S. aureus (MRSA) CC398
      obviously lost the IEC when evolving as livestock-associated MRSA from a human
      adapted, methicillin-susceptible ancestor. This study aimed to look for the
      presence of IEC in MRSA from pigs and horses as well as from the colonization of
      humans with occupational animal contact and from infections in humans. For
      comparison, methicillin susceptible S. aureus (MSSA) isolates from infections in
      humans were included. We did not detect the IEC among 94 isolates from the nasal
      colonization of pigs; however, the IEC was found in 6 of 61 isolates from
      nosocomial infections in horses. MRSA CC398 isolates from the nasal colonization
      of 138 pig farmers were negative for the IEC. It was detected, however, in 4 of
      69 veterinarians treating horses. Among 99 epidemiologically unrelated MRSA
      isolates attributed to CC398 originating from infections in humans, 19 were
      positive for the IEC. Only three of these isolates which also contained luk-PV
      were attributed to the ancestral, human-adapted subpopulation of CC398 by means
      of PCR for detection of canonical SNPs. A considerable proportion of LA-MRSA
      CC398 attributed to the animal subpopulation and originating from infections in
      humans had acquired the IEC; this acquisition is, however, obviously not a
      prerequisite to the capacity of LA-MRSA CC398 to cause infections in this host.
      Among 15 MSSA CC398 isolates from infections in humans, 11 contained the IEC, and
      of these, two were attributed to the animal subpopulation. Six isolates
      containing both the IEC and luk-PV were attributed to the ancestral, human
      subpopulation. Re-acquisition of the IEC by LA-MRSA CC398 suggests readaptation
      to the human host. In epidemiological surveillance, discrimination from the
      ancestral human subpopulation is important. 

PMID- 25778547
TI  - Levels, spatial variation and compartmentalization of trace elements in brown
      algae Cystoseira from marine protected areas of Crimea (Black Sea).
AB  - Levels of Al, Sc, V, Co, Ni, As, Br, Rb, Sr, Ag, Sb, I, Cs, Ba, Th and U that
      were rarely or never studied, as well as the concentrations of classically
      investigated Mn, Fe and Zn in brown algae Cystoseira barbata C. Ag. and
      Cystoseira crinita (Desf.) Bory from the coastal waters of marine protected areas
      (Crimea, Black Sea), were determined using neutron activation analysis. Spatial
      variation and compartmentalization were studied for all 19 trace elements (TE).
      Concentrations of most TE were higher in "branches" than in "stems". Spatial
      variations of V, Co, Ni and Zn can be related to anthropogenic activities while
      Al, Sc, Fe, Rb, Cs, Th and U varied depending on chemical peculiarities of the
      coastal zone rocks. TE concentrations in C. crinita from marine protected areas
      near Tarkhankut peninsula and Cape Fiolent, identified as the most clean water
      areas, are submitted as the background concentrations. 

PMID- 25778548
TI  - Probabilistic ecological risk assessment of copper in Chinese offshore marine
      environments from 2005 to 2012.
AB  - The objective of the present study was to conduct a probabilistic assessment of
      risk posed by copper found in the coastal marine environment of China from 2005
      to 2012. This was achieved by applying a tiered ecological risk assessment (ERA)
      approach for characterization of risks of concentrations of copper from
      nationwide marine water monitoring program. The results show that from 2005 to
      2012 the overall trend of hazard quotients (HQs) in the coastal marine
      environment of China the proportion of locations that exceed a HQ of 1.0
      decreased from 64% in 2005 to 31% in 2012. While this indicates an overall
      improvement of the environment, there still have potential ecological risks in
      the most of the area, especially for the major gulfs of Liaodong and Bohai Bays
      and Yellow River Estuary. In addition, probabilities of exceeding the toxicity
      threshold for 5% of species were 27.6%, 5.4%, 4.9%, 0.8%, 0.4%, 1.0%, 1.8% and
      0.12% annually between 2005 and 2012, respectively. 

PMID- 25778549
TI  - delta(13)C and delta(15)N in deep-living fishes and shrimps after the Deepwater
      Horizon oil spill, Gulf of Mexico.
AB  - The blowout of the Deepwater Horizon (DWH) drill-rig produced a surface oil
      layer, dispersed micro-droplets throughout the water column, and sub-surface
      plumes. We measured stable carbon and nitrogen isotopes in mesopelagic fishes and
      shrimps in the vicinity of DWH collected prior to, six weeks after, and one year
      after the oil spill (2007, 2010 and 2011). In 2010, the year of the oil spill, a
      small but significant depletion of delta(13)C was found in two mesopelagic fishes
      (Gonostoma elongatum and Chauliodus sloani) and one shrimp (Systellaspis
      debilis); a significant delta(15)N enrichment was identified in the same shrimp
      and in three fish species (G. elongatum, Ceratoscopelus warmingii, and
      Lepidophanes guentheri). The delta(15)N change did not suggest a change of
      trophic level, but did indicate a change in diet. The data suggest that carbon
      from the Deepwater Horizon oil spill was incorporated into the mesopelagic food
      web of the Gulf of Mexico. 

PMID- 25778550
TI  - Effect of electrical vs. chemical deep brain stimulation at midbrain sites on
      micturition in anaesthetized rats.
AB  - AIM: To understand how deep brain stimulation of the midbrain influences control
      of the urinary bladder. METHODS: In urethane-anaesthetized male rats, saline was
      infused continuously into the bladder to evoke cycles of filling and voiding. The
      effect of electrical (0.1-2.0 ms pulses, 5-180 Hz, 0.5-2.5 V) compared to
      chemical stimulation (microinjection of D,L-homocysteic acid, 50 nL 0.1 M
      solution) at the same midbrain sites was tested. RESULTS: Electrical stimulation
      of the periaqueductal grey matter and surrounding midbrain disrupted normal
      coordinated voiding activity in detrusor and sphincters muscles and suppressed
      urine output. The effect occurred within seconds was reversible and not secondary
      to cardiorespiratory changes. Bladder compliance remained unchanged. Chemical
      stimulation over the same area using microinjection of D,L-homocysteic acid (DLH)
      to preferentially activate somatodendritic receptors decreased the frequency of
      micturition but did not disrupt the coordinated pattern of voiding. In contrast,
      chemical stimulation within the caudal ventrolateral periaqueductal grey, in the
      area where critical synapses in the micturition reflex pathway are located,
      increased the frequency of micturition. CONCLUSION: Electrical deep brain
      stimulation within the midbrain can inhibit reflex micturition. We suggest that
      the applied stimulus entrained activity in the neural circuitry locally, thereby
      imposing an unphysiological pattern of activity. In a way similar to the use of
      electrical signals to 'jam' radio transmission, this may prevent a synchronized
      pattern of efferent activity being transmitted to the spinal outflows to
      orchestrate a coordinated voiding response. Further experiments to record
      neuronal firing in the midbrain during the deep brain stimulation will be
      necessary to test this hypothesis.

PMID- 25778551
TI  - Redox signaling in acute pancreatitis.
AB  - Acute pancreatitis is an inflammatory process of the pancreatic gland that
      eventually may lead to a severe systemic inflammatory response. A key event in
      pancreatic damage is the intracellular activation of NF-kappaB and zymogens,
      involving also calcium, cathepsins, pH disorders, autophagy, and cell death,
      particularly necrosis. This review focuses on the new role of redox signaling in
      acute pancreatitis. Oxidative stress and redox status are involved in the onset
      of acute pancreatitis and also in the development of the systemic inflammatory
      response, being glutathione depletion, xanthine oxidase activation, and thiol
      oxidation in proteins critical features of the disease in the pancreas. On the
      other hand, the release of extracellular hemoglobin into the circulation from the
      ascitic fluid in severe necrotizing pancreatitis enhances lipid peroxidation in
      plasma and the inflammatory infiltrate into the lung and up-regulates the HIF
      VEGF pathway, contributing to the systemic inflammatory response. Therefore,
      redox signaling and oxidative stress contribute to the local and systemic
      inflammatory response during acute pancreatitis. 

PMID- 25778613
TI  - RNA quaternary structure and global symmetry.
AB  - Many proteins associate into symmetric multisubunit complexes. Structural
      analyses suggested that, by contrast, virtually all RNAs with complex 3D
      structures function as asymmetric monomers. Recent crystal structures revealed
      that several biological RNAs exhibit global symmetry at the level of their
      tertiary and quaternary structures. Here we survey known examples of global RNA
      symmetry, including the true quaternary symmetry of the bacteriophage phi29
      prohead RNA (pRNA) and the internal pseudosymmetry of the single-chain flavin
      mononucleotide (FMN), glycine, and cyclic di-AMP (c-di-AMP) riboswitches. For
      these RNAs, global symmetry stabilizes the RNA fold, coordinates ligand-RNA
      interactions, and facilitates association with symmetric binding partners. 

PMID- 25778615
TI  - Effects of aripiprazole and haloperidol on neural activation during the n-back in
      healthy individuals: A functional MRI study.
AB  - OBJECTIVE: Antipsychotic drugs target neurotransmitter systems that play key
      roles in working memory. Therefore, they may be expected to modulate this
      cognitive function via their actions at receptors for these neurotransmitters.
      However, the precise effects of antipsychotic drugs on working memory function
      remain unclear. Most studies have been carried out in clinical populations,
      making it difficult to disentangle pharmacological effects from pathology-related
      brain activation. In this study, we aim to investigate the effects of two
      antipsychotic compounds on brain activation during working memory in healthy
      individuals. This would allow elucidation of the effects of current antipsychotic
      treatments on brain function, independently of either previous antipsychotic use
      or disease-related pathology. METHODS: We carried out a fully counterbalanced,
      randomised within-subject, double-blinded and placebo-controlled, cross-over
      study of the effects of two antipsychotic drugs on working memory function in 17
      healthy individuals, using the n-back task. Participants completed the functional
      MRI task on three separate occasions (in randomised order): following placebo,
      haloperidol, and aripiprazole. For each condition, working memory ability was
      investigated, and maps of neural activation were entered into a random effects
      general linear regression model to investigate main working memory function and
      linear load. Voxel-wise and region of interest analyses were conducted to attain
      regions of altered brain activation for each intervention. RESULTS: Aripiprazole
      did not lead to any changes in neural activation compared with placebo. However,
      reaction time to a correct response was significantly increased following
      aripiprazole compared to both placebo (p=0.046) and haloperidol (p=0.02). In
      contrast, compared to placebo, haloperidol dampened activation in parietal (BA
      7/40; left: FWE-corr. p=0.005; FWE-corr. right: p=0.007) and frontal (including
      prefrontal; BA 9/44/46; left: FWE-corr. p=0.009; right: FWE-corr. p=0.014)
      cortices and the left putamen (FWE-corr. p=0.004). Compared with aripiprazole,
      haloperidol dampened activation in parietal cortex (BA7/40; left: FWE-corr.
      p=0.034; right: FWE-corr. p=0.045) and the left putamen (FWE-corr.p=0.015).
      Haloperidol had no effect on working memory performance compared with placebo.
      CONCLUSION: Cognitive functions are known to be impaired in schizophrenia and as
      such are an important target of treatments. Elucidating the mechanisms by which
      antipsychotic medications alter brain activation underlying cognition is
      essential to advance pharmacological treatment of this disorder. Studies in
      healthy individuals can help elucidate some of these mechanisms, whilst limiting
      the confounding effect of the underlying disease-related pathology. Our study
      provides evidence for immediate and differential effects of single-dose
      haloperidol and aripiprazole on brain activation during working memory in healthy
      individuals. We propose that these differences likely reflect their different
      receptor affinity profiles, although the precise mechanisms underlying these
      differences remain unclear.

PMID- 25778614
TI  - SUMO-mediated regulation of DNA damage repair and responses.
AB  - Sumoylation has important roles during DNA damage repair and responses. Recent
      broad-scope and substrate-based studies have shed light on the regulation and
      significance of sumoylation during these processes. An emerging paradigm is that
      sumoylation of many DNA metabolism proteins is controlled by DNA engagement. Such
      'on-site modification' can explain low substrate modification levels and has
      important implications in sumoylation mechanisms and effects. New studies also
      suggest that sumoylation can regulate a process through an ensemble effect or via
      major substrates. Additionally, we describe new trends in the functional effects
      of sumoylation, such as bi-directional changes in biomolecule binding and
      multilevel coordination with other modifications. These emerging themes and
      models will stimulate our thinking and research in sumoylation and genome
      maintenance. 

PMID- 25778616
TI  - Can age at sexual maturity act as a predictive biomarker for prodromal negative
      symptoms?
AB  - BACKGROUND: Puberty and reproductive hormones have been identified as having a
      potential role in schizophrenia. Earlier reports have suggested associations
      between later age at puberty and schizophrenia in males. Similarly, associations
      have been reported between testosterone levels and psychotic symptoms. In this
      report, we examined the association between age at puberty and prodromal symptoms
      of psychosis. METHODS: 58 child or adolescent family members of individuals with
      schizophrenia were interviewed using the Scale of Prodromal Symptoms and the
      Tanner Maturational Scale. Age at Tanner pubertal stage was determined and
      regression analyses were used to explore associations between prodromal symptoms
      and age at puberty. RESULTS: Among males, delayed age at puberty was associated
      with greater severity of prodromal symptoms; the association between negative
      prodromal symptoms and delayed age was significant (p=0.001). In females, the
      association was not statistically significant. CONCLUSIONS: Our results suggest
      that delayed age at puberty may be associated with negative prodromal symptoms of
      schizophrenia in males. Our findings suggest that delayed age at puberty could
      potentially be a predictive biomarker for psychopathology in males at risk for
      schizophrenia.

PMID- 25778617
TI  - Genome-wide gene pathway analysis of psychotic illness symptom dimensions based
      on a new schizophrenia-specific model of the OPCRIT.
AB  - Empirically derived phenotypic measurements have the potential to enhance gene
      finding efforts in schizophrenia. Previous research based on factor analyses of
      symptoms has typically included schizoaffective cases. Deriving factor loadings
      from analysis of only narrowly defined schizophrenia cases could yield more
      sensitive factor scores for gene pathway and gene ontology analyses. Using an
      Irish family sample, this study 1) factor analyzed clinician-rated Operational
      Criteria Checklist items in cases with schizophrenia only, 2) scored the full
      sample based on these factor loadings, and 3) implemented genome-wide
      association, gene-based, and gene-pathway analysis of these SCZ-based symptom
      factors (final N=507). Three factors emerged from the analysis of the
      schizophrenia cases: a manic, a depressive, and a positive symptom factor. In
      gene-based analyses of these factors, multiple genes had q<0.01. Of particular
      interest are findings for PTPRG and WBP1L, both of which were previously
      implicated by the Psychiatric Genomics Consortium study of SCZ; results from this
      study suggest that variants in these genes might also act as modifiers of SCZ
      symptoms. Gene pathway analyses of the first factor indicated over-representation
      of glutamatergic transmission, GABA-A receptor, and cyclic GMP pathways. Results
      suggest that these pathways may have differential influence on affective symptom
      presentation in schizophrenia. 

PMID- 25778618
TI  - PART, a distinct tauopathy, different from classical sporadic Alzheimer disease.

PMID- 25778619
TI  - Extracellular vesicle sorting of alpha-Synuclein is regulated by sumoylation.
AB  - Extracellular alpha-Synuclein has been implicated in interneuronal propagation of
      disease pathology in Parkinson's Disease. How alpha-Synuclein is released into
      the extracellular space is still unclear. Here, we show that alpha-Synuclein is
      present in extracellular vesicles in the central nervous system. We find that
      sorting of alpha-Synuclein in extracellular vesicles is regulated by sumoylation
      and that sumoylation acts as a sorting factor for targeting of both, cytosolic
      and transmembrane proteins, to extracellular vesicles. We provide evidence that
      the SUMO-dependent sorting utilizes the endosomal sorting complex required for
      transport (ESCRT) by interaction with phosphoinositols. Ubiquitination of cargo
      proteins is so far the only known determinant for ESCRT-dependent sorting into
      the extracellular vesicle pathway. Our study reveals a function of SUMO protein
      modification as a Ubiquitin-independent ESCRT sorting signal, regulating the
      extracellular vesicle release of alpha-Synuclein. We deciphered in detail the
      molecular mechanism which directs alpha-Synuclein into extracellular vesicles
      which is of highest relevance for the understanding of Parkinson's disease
      pathogenesis and progression at the molecular level. We furthermore propose that
      sumo-dependent sorting constitutes a mechanism with more general implications for
      cell biology.

PMID- 25778620
TI  - Alterations of mGluR5 and its endogenous regulators Norbin, Tamalin and Preso1 in
      schizophrenia: towards a model of mGluR5 dysregulation.
AB  - Knockout of genes encoding metabotropic glutamate receptor 5 (mGluR5) or its
      endogenous regulators, such as Norbin, induce a schizophrenia-like phenotype in
      rodents, suggesting dysregulation of mGluR5 in schizophrenia. Human genetic and
      pharmacological animal studies support this hypothesis, but no studies have
      explored mGluR5 dysfunction at the molecular level in the postmortem
      schizophrenia brain. We assessed mGluR5 mRNA and protein levels in the
      dorsolateral prefrontal cortex (DLPFC) using a large cohort of schizophrenia and
      control subjects (n = 37/group), and additionally measured protein levels of
      recently discovered mGluR5 endogenous regulators, Norbin (neurochondrin), Tamalin
      (GRASP-1), and Preso1 (FRMPD4), which regulate mGluR5 localization,
      internalization and signaling. While mGluR5 mRNA expression was unchanged, mGluR5
      protein levels were significantly higher in schizophrenia subjects compared to
      controls (total: +22%; dimer: +54%; p < 0.001). Conversely, mGluR5 regulatory
      proteins were expressed at lower levels in schizophrenia subjects compared to
      controls (Norbin -37%, p < 0.001; Tamalin -30%, p = 0.084; Preso1 -29%, p =
      0.001). mGluR5 protein was significantly associated with mGluR5 mRNA and mGluR5
      endogenous regulators in control subjects, but these associations were lost in
      schizophrenia subjects. Lastly, there were no associations between protein
      measures and lifetime antipsychotic history in schizophrenia subjects. To confirm
      no antipsychotic influence, all proteins were measured in the prefrontal cortex
      of rats exposed to haloperidol or olanzapine; there were no effects of
      antipsychotic drug treatment on mGluR5, Norbin, Tamalin or Preso1. The results
      from our study provide compelling evidence that mGluR5 regulation is altered in
      schizophrenia, likely contributing to the altered glutamatergic signaling that is
      associated with the disorder.

PMID- 25778622
TI  - Everolimus-eluting Bioresorbable Vascular Scaffold Implantation in Real World and
      Complex Coronary Disease: Procedural and 30-day Outcomes at Two Australian
      Centres.
AB  - BACKGROUND: The Absorb BVS is a new generation of coronary stent designed to
      provide coronary arteries with mechanical support of a temporary nature,
      following balloon angioplasty. Clinical trials of the device have shown promising
      results thus far, however concern surrounds the deliverability of the device in
      real-world and complex coronary disease, and the possible higher incidence of
      early scaffold thrombosis when compared to conventional metallic drug-eluting
      stents. METHODS: Implantation of the Absorb BVS was attempted in 152 lesions in
      100 patients at two Sydney teaching hospitals, as part of a prospective registry.
      Lesions treated reflected a wide spectrum of real-world disease. Young patient
      age, long lesion length and involvement of the mid-portion of the left anterior
      descending artery were the strongest factors likely to influence the decision to
      use the Absorb BVS over conventional metallic stents. There were no restrictions
      on the lesion length, or on the number of lesions or vessels treated. Type C
      lesions made up 37% of all lesions treated with 64% of these being long lesions
      (>20mm). The Absorb BVS was successfully implanted in 98.8% of cases. Post
      dilatation was performed in 95% of scaffolds. Peri-procedural non-ST elevation
      myocardial infarction occurred in four cases. Scaffold thrombosis did not occur
      in any patient at 30 days follow-up. There was no death, or need for target
      lesion revascularisation in-hospital or at 30 days. CONCLUSIONS: High rates of
      procedural success were achieved with minimal complications with use of the
      Absorb BVS in real-world coronary disease, including complex disease. These
      results suggest that the reduced deliverability of the device can be largely
      overcome by meticulous lesion preparation, and that early scaffold thrombosis may
      be minimised through scaffold post-dilatation.

PMID- 25778621
TI  - Outcomes of On-Pump versus Off-Pump Coronary Artery Bypass Graft Surgery in the
      High Risk (AusSCORE > 5).
AB  - BACKGROUND: Coronary artery bypass graft surgery (CABG) has been established as
      the preferred intervention for coronary revascularisation in the high-risk
      population. Off-pump coronary artery bypass (OPCAB) may further reduce mortality
      and morbidity in this population subgroup. This study presents the largest series
      of high-risk (AusSCORE > 5) OPCAB patients in Australia and New Zealand. METHODS:
      We reviewed the Australian and New Zealand Society of Cardiac and Thoracic
      Surgeons' (ANZSCTS) database for high-risk patients (n=7822) undergoing isolated
      CABG surgery and compared the on-pump coronary artery bypass (ONCAB) (n=7277)
      with the OPCAB (n=545) technique. Preoperative and intraoperative risk factors,
      and postoperative outcomes were analysed. Survival analysis was performed after
      cross-matching the database with the national death registry to identify long
      term mortality. RESULTS: The ONCAB and OPCAB groups had similar risk profiles
      based on the AusSCORE. Thirty-day mortality (ONCAB vs OPCAB 3.9% vs 2.4%,
      p=0.067) and stroke (ONCAB vs OPCAB 2.4% vs 1.3%, p=0.104) were similar between
      the two groups. OPCAB patients received fewer distal anastomoses than ONCAB
      patients (2.5+/-1.2 vs 3.3+/-1.0, p<0.001). The rates of new postoperative atrial
      arrhythmia (28.3% vs 33.3%, p=0.017) and blood transfusion requirements (52.1% vs
      59.5%, p=0.001) were lower in the OPCAB group, while duration of ICU stay in
      hours (97.4+/-187.8 vs 70.2+/-152.8, p<0.001) was longer. There was a non
      significant trend towards improved 10-year survival in OPCAB patients (74.7% vs.
      71.7%, p=0.133). CONCLUSIONS: In the high-risk population, CABG surgery has a low
      rate of mortality and morbidity suggesting that surgery is a safe option for
      coronary revascularisation. OPCAB reduces postoperative morbidity and is a safe
      procedure for 30-day mortality, stroke and long-term survival in high-risk
      patients.

PMID- 25778623
TI  - Application of Clinical Databases to Contemporary Cardiac Surgery Practice: Where
      are We now?
AB  - Cardiac surgery has embraced and encouraged the use of large, multi-institutional
      datasets in clinical practice. From a research perspective, database studies have
      facilitated an increased understanding of cardiac surgery. Among other uses, they
      have allowed an investigation of disease incidence and mortality, high risk
      groups, disparities in health care delivery and the impact of new devices and
      techniques. Databases are also important tools for clinical governance and
      quality improvement. Despite their obvious utility, clinical databases have
      limitations; they are subject to treatment bias, contain missing data and cannot
      establish causality. Moreover, the ongoing maintenance of the database requires
      significant human and financial resources. In the future, inclusion of more
      detailed follow-up data and integration with other datasets will improve the
      utility of clinical databases. 

PMID- 25778624
TI  - Cardiac Vignette: Giant Left Atrial Appendage Aneurysm.
AB  - BACKGROUND: The left atrial appendage (LAA) is a vestigial structure located in
      the postero-lateral aspect of the left atrium. Aneurysmal enlargement of the LAA
      is pathological and can predispose to adverse events, including myocardial
      infarction, atrial fibrillation and systemic thromboembolism. The condition is
      rare and usually isolated, occurring in the absence of other cardiac defects. In
      this cardiac vignette, we describe a case of giant left atrial appendage in a
      middle aged female presenting with chest pain and explore the natural history,
      different investigative modalities as well as issues in clinical management of
      this condition.

PMID- 25778625
TI  - Endotoxin contamination of apolipoprotein A-I: effect on macrophage proliferation
      -a cautionary tale.
AB  - This technical report addresses the problem of endotoxin contamination of
      apolipoprotein reagents. Using a bromodeoxyuridine incorporation cell
      proliferation assay, we observed that human plasma ApoA-I as low as 1 MUg/ml
      resulted in a >90% inhibition in macrophage proliferation. However, not all ApoA
      I from different sources showed this effect. We considered the possibility that
      endotoxin contamination of the apolipoproteins contributed to the differential
      inhibition of macrophage cell proliferation. Endotoxin alone very potently
      inhibited macrophage proliferation (0.1 ng/ml inhibited macrophage
      proliferation>90%). Measurement of endotoxin levels in the apolipoprotein
      products, including an analysis of free versus total endotoxin, the latter which
      included endotoxin that was masked due to binding to protein, suggested that free
      endotoxin mediated inhibition of macrophage proliferation. Despite the use of an
      advanced endotoxin removal procedure and agents commonly used to inhibit
      endotoxin action, the potency of endotoxin precluded successful elimination of
      endotoxin effect. Our findings show that endotoxin contamination can
      significantly influence apparent apolipoprotein-mediated cell effects (or effects
      of any other biological products), especially when these products are tested on
      highly endotoxin-sensitive cells, such as macrophages.

PMID- 25778626
TI  - Anti-atherosclerotic activity of catechins depends on their stereoisomerism.
AB  - In terms of stereochemistry, catechins are divided into two groups: (-) epi forms
      (2R, 3R) and (-) forms (2S, 3R). Most of the catechins present in green tea are (
      ) epi forms (2R, 3R). Under the influence of high temperatures, in anaerobic
      conditions, as a result of epimerization the proportion of the (-) form (2S, 3R)
      increases. The data indicate that the presence of thermally modified catechins in
      the diet more efficiently reduces the development of atherosclerosis in apoE
      knockout mice than the presence of native catechins. The addition of the
      thermally modified formulations to the high-fat diet resulted in a reduction of
      the area of atherosclerotic lesions by about 28% (en face method) and 45% (cross
      section method) compared to the group fed the high-fat diet without catechins.
      Furthermore, the body weight gain and plasma TBARS concentration in mice fed a
      diet with the addition of catechins depends on the degree of epimerization of
      catechins and decreases with increasing content of catechins belonging to the (-)
      form (2S, 3R). Moreover, plasma HDL cholesterol concentration in mice depends on
      catechins' stereoisomerism and increases along with the increasing content of
      catechins belonging to the (-) form (2S, 3R). 

PMID- 25778627
TI  - Red cell distribution width is associated with endothelial progenitor cell
      depletion and vascular-related mediators in rheumatoid arthritis.
AB  - OBJECTIVES: The role of Red Cell Distribution Width (RDW) as a predictor of
      cardiovascular (CV) events has been proposed in a variety of conditions,
      including Rheumatoid Arthritis (RA). However, the mechanisms underlying this
      effect are still unknown. Since inflammation and Endothelial Progenitor Cells
      (EPCs) imbalance have been reported in RA patients to be related to CV disease,
      we wondered whether RDW could be linked to endothelial repair failure in RA.
      METHODS: EPCs (CD34+VEGFR2+CD133+) were quantified by flow cytometry in
      peripheral blood samples from 194 RA patients. IFNalpha, TNFalpha, IFNgamma, IL
      8, VEGF, GM-CSF, MCP-1, ICAM-1, EGF, Leptin and Resistin serum levels were
      quantified by immunoassays. Clinical and immunological parameters as well as
      history of traditional CV risk factors and CV events were registered from medical
      records. RDW was measured in complete blood cell count analyses. RESULTS: RDW was
      negatively related to EPC counts in patients with established disease (>1 year,
      n=125) (r=-0.306, p<0.001). Moreover, RDW was independently associated to an EPC
      depletion in the whole group (beta [95% CI]: -3.537 [-6.162, -0.911], p=0.009)
      after adjusting for clinical parameters, disease duration, treatments and
      traditional CV risk factors. Additionally, RDW was positively correlated with
      IFNalpha serum levels, a cytokine related to endothelial damage, and with IL-8,
      VEGF and neutrophil to lymphocyte ratio, thus supporting the association with
      inflammation and vascular remodelling. CONCLUSIONS: RDW was associated to EPC
      depletion and increased levels of different mediators linked to endothelial
      damage and vascular repair failure, thereby shedding new light on the nature of
      RDW as CV-predictor.

PMID- 25778628
TI  - Endovascular salvage for contained rupture of gastroduodenal artery aneurysm
      presented with obstructive jaundice.
AB  - Gastroduodenal artery (GDA) aneurysms are rare but lethal conditions when
      ruptures develop. Most common clinical presentation are gastrointestinal
      hemorrhage and abdominal pain. Obstructive jaundice is unusual. Computed
      tomography and angiography are useful tools for diagnosis and treatment plan. Any
      GDA aneurysm should be considered for definitive treatment. Recently,
      endovascular intervention has gained popularity for its safety and efficacy.
      Here, we described a patient of GDA pseudoaneurysm presented with generalized
      jaundice and was treated successfully with endovascular intervention.

PMID- 25778629
TI  - Carotenoid composition of the flowers of Mimulus lewisii and related species:
      Implications regarding the prevalence and origin of two unique, allenic pigments.
AB  - The genus Mimulus has been used as a model system in a wide range of ecological
      and evolutionary studies and contains many species with carotenoid pigmented
      flowers. However, the detailed carotenoid composition of these flowers has never
      been reported. In this paper the floral carotenoid composition of 11 Mimulus
      species are characterized using high-performance liquid chromatography, mass
      spectrometry and chemical methods with a particular focus on the genetic model
      species, Mimulus lewisii. M. lewisii flowers have five major carotenoids:
      antheraxanthin, violaxanthin, neoxanthin, and the unique allenic carotenoids,
      deepoxyneoxanthin and mimulaxanthin. This carotenoid profile is consistent with
      the expression levels of putative carotenoid biosynthetic genes in the M. lewisii
      flower. The other 10 species possess the same five carotenoids or a subset of
      these. Comparison of the carotenoid profiles among species in a phylogenetic
      context provides new insights into the biosynthesis and evolution of
      deepoxyneoxanthin and mimulaxanthin. This work also lays the foundation for
      future studies regarding transcriptional control of the carotenoid biosynthesis
      pathway in Mimulus flowers. 

PMID- 25778631
TI  - Is it time to revisit contraindications to organ donation from donors with a JAK
      2 mutation? Safe use of a liver allograft from a donor with essential
      thrombocythaemia.
AB  - Transplantation can cure end-stage liver disease and hepatocellular carcinoma.
      However, the balance of organ demand and provision is heavily tipped to the
      detriment of patients. Patients awaiting transplantation rely on the greater use
      of marginal donors that may carry a risk to the recipient. UK authorities have
      decreed donor haematological malignancy an absolute contraindication. The authors
      describe the first report of a patient being safely transplanted with a liver
      from a donor who suffered from JAK2 V617F mutation-driven essential
      thrombocythaemia to a patient with a critical burden of hepatocellular carcinoma.
      A year after transplantation, the patient has neither evidence of acquisition of
      the donor's pathology, nor evidence of carcinoma recurrence. The case highlights
      the responsibility of the recipient team to maximize the use of organs by expert
      risk assessment. Dissemination of experience should inform future decisions,
      benefit patients and bolster utility in an era of growing waiting-list mortality.

PMID- 25778632
TI  - Re: MRI findings of radiation-induced myocardial damage in patients with
      oesophageal cancer. A reply.

PMID- 25778630
TI  - Substrate, product, and cofactor: The extraordinarily flexible relationship
      between the CDE superfamily and heme.
AB  - PFam Clan 0032, also known as the CDE superfamily, is a diverse group of at least
      20 protein families sharing a common alpha,beta-barrel domain. Of these, six
      different groups bind heme inside the barrel's interior, using it alternately as
      a cofactor, substrate, or product. Focusing on these six, an integrated picture
      of structure, sequence, taxonomy, and mechanism is presented here, detailing how
      a single structural motif might be able to mediate such an array of functions
      with one of nature's most important small molecules. 

PMID- 25778633
TI  - Combined lesions of direct and indirect basal ganglia pathways but not changes in
      dopamine levels explain learning deficits in patients with Huntington's disease.
AB  - Huntington's disease (HD) is a hereditary neurodegenerative disease of the basal
      ganglia that causes severe motor, cognitive and emotional dysfunctions. In the
      human basal ganglia, these dysfunctions are accompanied by a loss of striatal
      medium spiny neurons, dysfunctions of the subthalamic nucleus and globus
      pallidus, and changes in dopamine receptor binding. Here, we used a neuro
      computational model to investigate which of these basal ganglia dysfunctions can
      explain patients' deficits in different stimulus-response learning paradigms. We
      show that these paradigms are particularly suitable for scrutinising the effects
      of potential changes in dopamine signaling and of potential basal ganglia lesions
      on overt behavior in HD. We find that combined lesions of direct and indirect
      basal ganglia pathways, but none of these lesions alone, reproduce patients'
      learning impairments. Degeneration of medium spiny neurons of the direct pathway
      accounts for patients' deficits in facilitating correct responses, whereas
      degeneration of indirect pathway medium spiny neurons explains their impairments
      in inhibiting dominant but incorrect responses. The empirical results cannot be
      explained by lesions of the subthalamic nucleus, which is part of the hyperdirect
      pathway, or by changes in dopamine levels. Overall, our simulations suggest
      combined lesions of direct and indirect pathways as a major source of HD
      patients' learning impairments and, tentatively, also their motor and cognitive
      deficits in general, whereas changes in dopamine levels are suggested to not be
      causally related to patients' impairments. 

PMID- 25778634
TI  - [Treatment of angiolymphoid hyperplasia with eosinophilia (ALHE) using topical
      tacrolimus: Two cases].
AB  - BACKGROUND: Angiolymphoid hyperplasia with eosinophilia (ALHE) is a rare disease,
      currently considered a benign vascular proliferation of unknown etiology, and
      whose treatment is still unclear and challenging. PATIENTS AND METHODS: Two women
      in their thirties consulted for itchy lesions of the right ear. Both presented
      with a reddish bleeding papulonodular infiltration of the auricle, with a nodule
      at the entrance to the external auditory canal in the first patient. Laboratory
      tests showed no abnormalities and in particular no hypereosinophilia or elevated
      serum immunoglobulin E. In both cases, histology of lesional skin showed vascular
      proliferation with thick-walled vessels lined by plump endothelial cells,
      protruding into the lumen, together with a mixed dermal inflammatory infiltrate
      consisting primarily of eosinophils and lymphocytes. A diagnosis of ALHE was made
      in both patients based on clinical and histological features. MRA revealed no
      underlying vascular malformation in both cases. Patients started treatment with
      0.1% tacrolimus ointment twice daily. The pruritic sensation and bleeding had
      completely subsided within two weeks and the reddish infiltration and nodules had
      practically disappeared after two months of topical tacrolimus. Continuous
      application resulted in no recurrence at 6 months of follow-up. DISCUSSION:
      Treatment of ALHE is still poorly standardized due to doubts concerning the
      pathophysiology of this rare condition and the small number of available studies.
      Topical tacrolimus was originally developed for the treatment of moderate to
      severe atopic dermatitis because of its anti-inflammatory and immunomodulatory
      properties. Recent studies suggest that this drug may be effective in treating
      other forms of inflammatory dermatosis. Our two observations suggest that
      tacrolimus ointment also represents potentially valuable treatment in AHLE.

PMID- 25778635
TI  - [Massive localized lymphedema].
AB  - BACKGROUND: Massive localized lymphedema (MLL) is a benign soft-tissue lesion
      that usually presents as a large and isolated mass in morbidly obese adults.
      PATIENTS AND METHODS: We report the case of a 39-year-old woman presenting
      obesity and multiple MLL. There was a large tumor in the left groin and two
      smaller lesions on the backs of the thighs. DISCUSSION: MLL is a benign tumor
      that must be removed wherever possible because such tumors may degenerate into
      angiosarcomas in 13% of cases. MLL is probably secondary to a prolonged
      obstruction of lymphatic vessels due to marked excess of adipose tissue.

PMID- 25778636
TI  - [Emotional distress and quality of life in people with diabetes and their
      families].
AB  - OBJECTIVE: The daily experience of living with diabetes can adversely affect the
      quality of life of people with diabetes and their families. We present the
      results for Spain of the DAWN2 study related to quality of life and wellbeing of
      patients and their families. METHODS: The DAWN2 study is an observational, cross
      sectional study. In the present study, we used the Spanish sample of patients
      (N=502) and their relatives (N=123). RESULTS: A total of 13.9% of patients were
      at risk of possible depression while 50.0% of people with diabetes and 45.5% of
      family members reported a high level of diabetes-related emotional stress.
      CONCLUSIONS: People with diabetes experience high levels of stress and the
      psychosocial impact of diabetes also affects family members.

PMID- 25778637
TI  - [Control measures for anabolic androgenic steroid medicines].
AB  - Anabolic androgenic steroids (AAS) can cause serious adverse effects when used
      without a therapeutic purpose. This article aims to show that the AAS are
      susceptible to being sold on the black market. We also aim to describe how
      certain limitations on the health inspection services of the Galician health
      service to pursue these illegal actions prompted a regulatory initiative
      demanding that additional actions be granted to community pharmacies when
      dispensing AAS. Four pharmacy inspections detected the diversion of a total of
      3118 packages of AAS, which led to the opening of four disciplinary proceedings.
      In two of these, specialized police forces were called in as there was sufficient
      evidence of possible diversion to gymnasiums, resulting in a police operation
      called Operation Fitness. 

PMID- 25778638
TI  - Effect of peptide agonists of peripheral opioid receptors on operant feeding
      behavior and food motivation in rats.
AB  - We studied the effect of intragastric administration of peptide agonists of MU
      opioid receptors (DAMGO) and delta-opioid receptors (DADLE) on food consumption
      and food motivation during operant feeding behavior of different intensity and
      effectiveness. To obtain one food granule, trained rats should press a lever 1
      time (day 1), 2 times (day 2), 4 times (day 3), 8 times (day 4), 16 times (day
      5), or 32 times (day 6). Activation of delta-opioid receptors in the stomach was
      followed by suppression of feeding behavior at low energy expenditure. The level
      of food motivation under these conditions practically did not differ from the
      control. Activation of MU-opioid receptors in the stomach suppressed energy
      consuming feeding behavior, which was accompanied by an increase in the level of
      food motivation. It can be hypothesized that protein metabolites exhibiting MU
      opioid activity probably provide afferent signals into CNS via the vagus nerve to
      terminate energy expenditure under adverse conditions (although food motivation
      is not satisfied). Food motivation under these conditions probably contributes to
      the behavior aimed towards the search for more available food. 

PMID- 25778639
TI  - Involvement of protein kinase Mzeta in the maintenance of long-term memory for
      taste aversion learning in young chicks.
AB  - The effects of an inhibitor of protein kinase Mzeta on long-term memory were
      studied using the model of taste aversion in newborn chicks. Memory was impaired
      by intracerebral injection of 10 or 20 nmol of zeta-inhibiting peptide 24 h after
      training. Memory impairment was found 2 h after peptide administration, and
      repeated examination 24 h after treatment showed no recovery. Memory impairment
      was not observed 24 h after inhibitor administration if the testing 2 h after
      treatment was not performed. The results indicate the contribution of protein
      kinase Mzeta in the maintenance of long-term memory in the avian brain. These
      data confirm the hypothesis of several authors that inhibition of protein kinase
      Mzeta does not abolish memory, but rather interacts with processes of memory
      retrieval and/or reconsolidation. 

PMID- 25778640
TI  - Effect of interleukin-4 on peripheral blood leukocytes in rats with various
      behavioral characteristics during acute stress.
AB  - We studied the effect of anti-inflammatory cytokine IL-4 (5 MUg/kg
      intraperitoneally) on peripheral blood leukocytes in Wistar rats with various
      behavioral characteristics during acute emotional stress (1-h immobilization with
      simultaneous subthreshold electrocutaneous stimulation). IL-4 reduced the
      differences in blood leukocyte count in rats with various behavioral
      characteristics, which was related to a significant decrease in this parameter in
      active animals. IL-4 injection to active animals was accompanied by changes in
      the leukogram (development of neutrophilia, monocytopenia, and lymphopenia) and
      had a modulatory effect on leukocyte indexes of cell reactivity. Blood leukocyte
      count in cytokine-treated animals did not change after stress exposure. IL-4
      prevented shifts in leukocyte indexes of cell reactivity, which was found after
      acute stress exposure. Our results expand current notions on the specific
      involvement of endogenous immunomodulatory compounds in the realization of
      adaptive and compensatory processes in mammals during negative emotiogenic
      exposures.

PMID- 25778641
TI  - Changes in electrical activity of working myocardium under condition of if
      current inhibition.
AB  - The study examined the effect of ZD7288, a blocker of hyperpolarization-activated
      "funny" current If, on electrical activity in working atrial and ventricular
      myocardium in rats. In concentrations range from 3*10(-6) to 3*10(-5) M, the
      agent significantly increased the duration of action potentials at 50 and 90%
      repolarization levels in both atrial and ventricular myocardium at the fixed
      stimulation rate of 5 Hz. The blocker affected neither resting potential nor the
      upstroke velocity of action potential. In patch-clamp experiments, ZD7288
      selectively inhibited If current, but produced no effect on delayed rectifier
      potassium currents that determine the rate of repolarization. The described
      effects of ZD7288 are not related to its non-specific effects on the ionic
      currents except If.

PMID- 25778642
TI  - Molecular markers of arterial hypertension in patients with normotony, pre
      hypertension and hypertension.
AB  - We studied concentrations of angiotensin II, HLDF24 peptide, endothelin proteins,
      S100B, and autoantibodies to them and serum levels of blood natriuretic peptide
      in patients with different categories of "normal" arterial BP and hypertension.
      The relationship between blood levels of the above factors and normotony, pre
      hypertension, and hypertension in the examined groups was analyzed. The results
      suggest that the studied molecular factors can serve as potential predictors of
      arterial hypertension and used for personalized hypertension risk assessment.

PMID- 25778643
TI  - Behavioral, hormonal, and neurotransmitter reactions to stress in adult rats with
      a history of high IL-1beta content in the early postnatal ontogeny.
AB  - Behavioral, hormonal, and neurotransmitter reactions to foot shock were studied
      in adult rats treated with IL-1beta during week 3 of life. After stress, these
      animals differed from controls treated with saline by high levels of dopamine,
      serotonin, and 5-hydroxy-indolacetic acid in the hypothalamus. In contrast to
      controls, they developed a significant stress-induced increase of blood
      corticosterone level and exhibited lesser motor and exploratory activities in the
      open field test. 

PMID- 25778644
TI  - Diffusion in the corpus callosum in patients with early schizophrenia.
AB  - Diffusion in the cerebral corpus callosum in patients with early schizophrenia
      was studied by diffusion tensor MRT and magnetic resonance spectroscopy. The
      fraction anisotropy coefficient in the corpus callosum knee was low as a result
      of high radial diffusion. Spectroscopy detected a decrease of N-acetylaspartate
      level in the corpus callosum knee indicating axonal lesion during the early stage
      of schizophrenia. 

PMID- 25778645
TI  - Study on activity of inflammatory factors in patients with chronic heart failure
      depending on the stage of the disease and NYHA class.
AB  - The levels of IL-8 and IL-10 and their ratio depending on the stage and NYHA
      functional class of heart failure were determined in the patients with chronic
      heart failure in comparison with healthy individuals. The level of IL-8 and IL
      8/IL-10 ratio in patients were significantly higher than in controls, and the
      level of IL-10, significantly lower. The comparison of cytokine levels in
      patients at different stages of heart failure and NYHA class revealed no
      significant differences. However, the level of IL-10 tended to decrease by stage
      3 of the disease. Significantly elevated IL-8 level along with reduced IL-10
      level and significantly increased IL-8/IL-10 ratio indicated predominance of
      proinflammatory activity in patients with chronic heart failure, which along with
      the tendency to decrease IL-10 level at stage 3 of the disease may indicate the
      ineffectiveness of compensatory mechanisms and progressive "failure" of
      compensation with increasing severity of the disease. 

PMID- 25778646
TI  - Levocarnitine normalizes elevated blood level of soluble Fas mRNA in patients
      with acute myocardial infarction.
AB  - Fas-induced apoptosis plays an important role in the mechanisms of tissue injury
      in myocardial infarction. The level of membrane Fas mRNA was elevated during the
      postinfarction period in the blood of patients and did not change in response to
      levocarnitine. The mRNA level of soluble Fas, inhibiting Fas-dependent apoptosis,
      remained normal during the first 7 days, but increased 14 days after myocardial
      infarction, which corresponded to previously detected increase of serum level of
      soluble Fas molecules. Addition of levocarnitine, inhibiting Fas-dependent
      apoptosis, to therapy caused no changes in the level of soluble Fas mRNA,
      presumably because of similar effects of soluble Fas and levocarnitine on the
      apoptotic processes in myocardial infarction. 

PMID- 25778647
TI  - Role of NF-kappaB/IKK-dependent signaling in functional stimulation of
      mesenchymal progenitor cells by alkaloid songorine.
AB  - We studied the role of NF-kappaB/IKK-mediated signaling in the stimulation of
      growth potential of mesenchymal progenitor cells by alkaloid songorine in vitro.
      Specific NF-kappaB inhibitor oridonin abolished activation of proliferation and
      differentiation of progenitor cells. Aurothiomalate, a selective blocker of IKK
      2, also suppressed mitotic activity of fibroblast precursors, but had no effect
      on the rate of the differentiation.

PMID- 25778648
TI  - Effectiveness of composition based on oxidized dextran in the treatment of grade
      IIIB skin burns.
AB  - Grade IIIB skin burns were treated with a composition based on oxidized dextran
      with a molecular weight of 40 kDa (oxidation of 7% glucose residues). On day 32
      after burn infliction and from the start of the treatment, the area of skin
      defect in rats was 30% less than in the group without treatment and by 2.3 times
      less than in rats treated with panthenol. In rats treated with dextran-based
      composition or panthenol, the eschar was absent on day 21 after the start of the
      treatment; by day 32, we found cells of surface epithelium, hair follicles, and
      sebaceous glands above the scar tissue that were absent in untreated animals; in
      rats treated with the composition, their number was higher by 2.5 times than in
      animals treated with panthenol. Treatment with the composition increased volume
      density (by 2.5 times) and numerical density (by more than 3 times) of blood
      vessels in the wound and reduced signs of inflammation and fibroplastic activity
      of fibroblasts in comparison with the corresponding parameters in untreated
      animals or animals treated with panthenol. 

PMID- 25778649
TI  - Content of circulating extracellular DNA, plasma activities of matrix
      metalloproteinases, and ultrastructure of the myocardium in hypothyroid rats with
      hypercholesterolemia.
AB  - Free circulating extracellular DNA, plasma activities of matrix
      metalloproteinases in hypothyroid rats, and ultrastructural changes in the
      myocardium were studied under conditions of experimental hypercholesterolemia.
      For suppression of thyroid function, the animals received antithyroid drug
      mercazolyl under conditions of cholesterol diet. Hypercholesterolemia in
      hypothyroid rats (thyroxine concentration 2-fold below the normal) was paralleled
      by a pronounced increase of the concentration of free circulating extracellular
      DNA and total matrix metalloproteinases 2 and 7 activity. These changes were
      associated with lytic and destructive changes in cardiomyocytes and blood
      capillary endotheliocytes. Changes in the cardiomyocyte and endotheliocyte
      ultrastructure were more pronounced in hypothyroid rats. 

PMID- 25778650
TI  - Serum levels of neurosteroids in patients with affective disorders.
AB  - According modern biological hypotheses of the pathogenesis of affective
      disorders, hypothalamic-pituitary-adrenal axis dysfunction play a special role in
      the pathogenesis of this condition. Our study shows that the range of
      neuroprotective neurosteroids is gender- and nosology-dependent. Patients with
      affective disorders have reduced levels of dehydroepiandrosterone and
      dehydroepiandrosterone sulfate; the most pronounced deficiency of neuroprotective
      neurosteroids is typical of patients with a single depressive episode. Reduced
      levels of neurosteroids producing an anabolic effect probably indicate depletion
      of adaptive capacities of the hypothalamic-pituitary-adrenal system in affective
      disorders.

PMID- 25778651
TI  - Transformation of catalytic characteristics of cerebral monoamine oxidases in
      experimental posttraumatic stress disorders.
AB  - We studied the contribution of the transformation of the catalytic properties of
      cerebral monoamine oxidase in the development of behavioral disorders during
      stress. Monoamine oxidase activities and catalytic characteristics, LPO
      intensity, and oxidative modification of proteins in suspension of the brain
      mitochondria were evaluated over the course of experimental posttraumatic stress
      disorder. The detected shifts were comparable with the results of neuroethologic
      testing. The development of behavioral disorders presented by low exploratory
      activity and high anxiety was associated with transformation of catalytic
      characteristics of cerebral monoamine oxidases, associated with the development
      of oxidative stress with predominant intensification of metal-catalyzed protein
      oxidation.

PMID- 25778652
TI  - Synergetic fMRI-EEG brain mapping in alpha-rhythm voluntary control mode.
AB  - For the first time in neurobiology-related issues, the synergistic spatial
      dynamics of EEG and fMRI (BOLD phenomenon) was studied during cognitive alpha
      biofeedback training in the operant conditioning mode (acoustic reinforcement of
      alpha-rhythm development and stability). Significant changes in alpha-rhythm
      intensity were found in T6 electrode area (Brodmann area 37). Brodmann areas
      related to solving alpha-training tasks and maximally involved in the formation
      of new neuronal network were middle and superior temporal gyri (areas 21, 22, and
      37), fusiform gyrus, inferior frontal gyrus (areas 4, 6, and 46), anterior
      cingulate gyrus (areas 23 and 24), cuneus, and precuneus (area 7). Wide
      involvement of Brodmann areas is determined by psychological architecture of
      alpha-rhythm generating system control that includes complex cognitive
      activities: decision making, retrieval of long-term memory, evaluation of the
      reward and control efficiency during alpha-EEG biofeedback. 

PMID- 25778653
TI  - Pathways of apoptosis regulation in hepatocytes induced by first-line
      antitubercular drugs.
AB  - We studied pathways of apoptosis regulation during experimental hepatopathy
      caused by treatment with antitubercular drugs and involvement of some
      hepatoprotectors and immunomodulators in the regulation of hepatocyte apoptosis
      induced by antitubercular drugs. The intensity of apoptosis and expression of
      apoptosis-associated molecules were evaluated. It was shown that antitubercular
      drugs induce apoptosis in hepatocytes by triggering external signaling pathway
      and p53-dependent signaling pathway and simultaneously reducing the level of anti
      apoptotic Bcl-2 protein. Runihol, remaxol, and cycloferon reduced degenerative
      effects in the liver, though the level of apoptosis remained high. Ademetionine
      in tablets and reamberin improved the microstructure of the liver by inhibiting
      both apoptotic pathways induced by the antitubercular drugs; in other words, they
      have distinct hepatoprotective and apoptosis-protective effects, which is
      especially important at the late stages of ontogeny.

PMID- 25778654
TI  - Prenatal effects of peat combustion products and afobazole correction thereof in
      the rat progeny.
AB  - Female outbred albino rats were daily subjected to forced inhalations of peat
      smoke (4 cores packed with a mixture of peat (70%) and wood pulp (30%); 0.46 g,
      pH >= 5.5) per se and in combination with oral afobazole (anxiolytic) on days 1
      20 of pregnancy. Exposure to peat smoke inhibited body weight gain in pregnant
      rats, caused an increase of postimplantation deaths, reduction of fetal weights,
      and an increase in the number of hematomas and hemorrhages in fetuses. Afobazole
      in doses of 1 and 10 mg/kg reduced significantly the untoward effects of peat
      smoke on fetal development.

PMID- 25778655
TI  - Afobazole protects rats exposed to peat smoke in utero.
AB  - Female outbred albino rats were daily subjected to forced inhalations of peat
      smoke (4 cores packed with a mixture of peat (70%) and wood pulp (30%); 0.46 g,
      pH at least 5.5, core burning time 6 min,; total exposure 44 min) per se and in
      combination with oral afobazole (anxiolytic) in doses of 1 and 10 mg/kg on days 1
      20 of pregnancy. Some groups of females received oral afobazole (200 mg/kg) after
      delivery, due to which their newborn rats received the drug in doses of 1-10
      mg/kg with maternal milk on days 1-20 of life. Exposure to peat smoke inhibited
      body weight gain in the progeny on days 5-60 of life. Afobazole treatment during
      the pre- and postnatal periods prevented this effect. Open field testing showed
      that exposure to peat smoke prolonged the motor activity in the progeny and
      impaired the loss of orientation and exploratory behavior during repeated
      testing. Oral afobazole (1 and 10 mg/kg) during the prenatal and/or postnatal
      period (with maternal milk) prevented the effects of peat smoke. 

PMID- 25778656
TI  - Efficiency of recombinant thymosin beta4 in spontaneous mouse model of chronic
      dermatitis.
AB  - The therapeutic efficiency of recombinant thymosin beta4 (rTbeta4) synthesized by
      us was studied in vivo on spontaneous CBRB mouse model that is adequate to human
      chronic dermatitis. Three applications of the drug during a week significantly
      alleviated symptoms of the disease in female mice, and in complex with subsequent
      antibacterial and antifungal therapy led to a pronounced and lasting (2 months)
      therapeutic effect. The results attest to a possibility of using rTbeta4 in
      combination with the known treatment protocols for chronic inflammatory diseases
      of the skin.

PMID- 25778657
TI  - Polymorphisms of the anti-inflammatory IL-10 gene associated with malignancy in
      female reproductive system.
AB  - Association of three polymorphisms (1082G/A, 819C/T, and 592C/A) of the promotor
      region of the anti-inflammatory IL-10 gene with malignancy of female reproductive
      organs was revealed by SNP (single nucleotide polymorphism) method in ethnic
      groups of Adygei Republic. Breast cancer, cervical cancer, and cancer of the
      uterine corpus are associated with allele 592A (r=0.042) in Circassians and with
      polymorphism 819T in Russians (r=0.046). Irrespective of the ethnicity, allele
      819T was signifi cantly more often (r<0.05) detected in prevalent forms of breast
      cancer involving regional lymph nodes. 1082G polymorphism is associated with low
      differentiated adenocarcinoma. In women of Adygei Republic, ATA/GCA gaplotypes
      are associated with high risk factors for breast cancer.

PMID- 25778658
TI  - Expression of vascular endothelial growth factor (VEGF-A) in rat mandibular
      salivary gland during paraneoplastic process and treatment with cyclophosphamide
      and melatonin.
AB  - Expression of VEGF-A in Walker 256 carcinosarcoma and mandibular salivary gland
      of rats during paraneoplastic process and various regimens of chemotherapy with
      melatonin and cyclophosphamide were studied by immunohistochemical methods. VEGF
      A expression increased in the tumor node and salivary gland after monotherapy
      with melatonin and cyclophosphamide during progression of tumor growth and
      paraneoplastic syndrome. A decrease in VEGF-A expression in the tumor node and
      salivary gland was found after monotherapy with melatonin and cyclophosphamide
      and, especially, after combined treatment, which proves maximum therapeutic
      efficiency of combined administration of chemical agents with various mechanisms
      of action. Overexpression of VEGF-A in the mandibular salivary gland can have
      diagnostic and predictive value in early diagnostics of neoplasms. 

PMID- 25778659
TI  - Comparison of treatment options for experimental endometriosis in rats.
AB  - The effectiveness of surgery, immunomodulator "Vilon" therapy, and their
      combination in the treatment of experimental endometriosis in rats was assessed
      by the parameters of reproductive function. The experiments demonstrated that
      surgery combined with intraperitoneal application of "Vilon" is a promising
      option in the treatment of endometriosis.

PMID- 25778660
TI  - Evaluation of fibrogenic potential of industrial multi-walled carbon nanotubes in
      acute aspiration experiment.
AB  - Local inflammatory response in the lungs and fi brogenic potential of multi
      walled carbon nanotubes were studied in an acute aspiration experiment in mice.
      The doses were chosen based on the concentration of nanotubes in the air at a
      workplace of the company-producer. ELISA, fl ow cytometry, enhanced darkfield
      microscopy, and histological examination showed that multi-walled carbon
      nanotubes induced local inflammation, oxidative stress, and connective tissue
      growth (fibrosis). Serum levels of TGF-beta1 and osteopontin proteins can serve
      as potential exposure biomarkers.

PMID- 25778661
TI  - Effects of acoustic and EHF impulses on multipotent stromal cells during
      formation of bone marrow containing heterotopic organs in tissue engineered
      constructions.
AB  - We studied the effects of physical factors (acoustic impulses of laser-induced
      hydrodynamics, AILIH, and EHF-radiation) on the formation of heterotopic bone
      marrow organs. Suspension of precipitated mouse bone marrow cells was exposed to
      AILIH and EHF or their combinations (AILIH+EHF, EHF+AILIH). The developed tissue
      engineering constructions (gelatin sponges containing 107 nucleated bone marrow
      cells exposed to physical factors) were transplanted under the renal capsule of
      syngeneic mice. Analysis of newly formed hemopoietic organs was performed after 3
      and 5 months. The total amount of hemopoietic cells, number of multipotent
      stromal cells, efficiency of colony formation from these cells, and weight of
      bone capsule of the transplants were measured. Microscopic study showed that 5
      month transplants were significantly larger than 3-month transplants and
      contained 3-fold more hemopoietic cells (20-fold in the AILIH+EHF group). The
      number of multipotent stromal cells was maximum in EHF+AILIH group (by 2.2 times
      higher than in the control) and minimum in AILIH+EHF group. Exposure to EHF+AILIH
      had most pronounced effect on the formation of the bone marrow transplants. The
      weight of bone capsules more rapidly increased in gelatin sponges of 3-month
      transplants of EHF+AILIH and AILIH groups. These data suggest that the studied
      physical factors can be used for acceleration of rehabilitation process.

PMID- 25778662
TI  - Metal nanoparticles reduce bacterial contamination of experimental purulent
      wounds.
AB  - Bacterial contamination of experimental purulent wound in rats treated by local
      applications of suspension of copper and zinc nanoparticles and a combined drug
      based on chitosan and copper and zinc nanoparticles was evaluated. Applications
      of copper nanoparticle suspension and combined drug with copper and zinc
      nanoparticles and chitosan led to rapid elimination of the bacterial contaminant.
      Antibacterial activity of zinc nanoparticles was less pronounced, but the effect
      also differed significantly from the reference group. 

PMID- 25778663
TI  - Norepinephrinergic and nitroxidergic neurons of vasomotor nuclei in hypertensive
      rats.
AB  - The distributions of norepinephrinergic and nitroxidergic neurons in solitary
      tract nucleus, locus coeruleus, and in the small-celled and gigantocellular
      reticular nuclei were examined in sham-operated and experimental Wistar rats with
      induced renovascular hypertension. In control rats, the greatest population of
      norepinephrinergic cells was revealed in the projections of locus coeruleus and
      reticular gigantocellular nuclei, while the larger number of nitroxidergic
      neurons were observed in the solitary tract and the small-celled nuclei. During
      renovascular hypertension, the earliest and the most pronounced changes in
      luminescence intensity and the number of nitroxidergic neurons were observed in
      the solitary tract nucleus, while the changes in locus coeruleus were minimal.
      The significant changes in similar parameters of norepinephrinergic neurons were
      documented only in reticular gigantocellular nucleus and locus coeruleus, but
      they were delayed and less pronounced in comparison with the changes of
      nitroxidergic neurons.

PMID- 25778664
TI  - Molecular modeling as a new approach to the development of urokinase inhibitors.
AB  - Proteolytic activity of urokinase plays an important role in negative remodeling
      of blood vessels, restenosis, tumor angiogenesis, and metastasizing, which
      necessitates the development of selective urokinase inhibitors. Using methods of
      computer modeling (docking, post processing, and direct docking) and quantum
      chemistry, we selected substances from the large compound database, analyzed
      their structures, and experimentally verified their inhibitor activity. New
      urokinase inhibitor candidates were proposed based on the theoretical predictions
      and experimental verification of compound activities. The process of modifying
      urokinase inhibitors based on (benzothiazol-3-yl)guanidine was developed. A new
      urokinase inhibitor (5-brom-benzothiazol-3-yl)guanidine, that can be effective
      for regulation of vascular remodeling and tumor angiogenesis, was created.

PMID- 25778665
TI  - Nootropic effect of meadowsweet (Filipendula vulgaris) extracts.
AB  - The effects of the extracts of the aboveground parts of Filipendula vulgaris
      Moench on the behavior and memory of mice after hypoxic injury and their physical
      performance in the open-field test were studied using the models of hypoxia in a
      sealed volume, conditioned passive avoidance response (CPAR), and forced swimming
      with a load. The extracts improved animal resistance to hypoxia, normalized
      orientation and exploration activities, promoted CPAR retention after hypoxic
      injury, and increased physical performance. Aqueous extract of meadowsweet had
      the most pronounced effect that corresponded to the effect of the reference drug
      piracetam. These effects were probably caused by modulation of hippocampal
      activity. 

PMID- 25778666
TI  - [Doubts on the justification for universal screening for cytomegalovirus
      infection in premature neonates less than 1,500 g].

PMID- 25778668
TI  - Dihydroartemisinin inhibits endothelial cell proliferation through the
      suppression of the ERK signaling pathway.
AB  - Disrupting tumor angiogenesis serves as an important strategy for cancer therapy.
      Dihydroartemisinin (DHA), a semi-synthetic derivative of artemisinin, has
      exhibited potent anti-angiogenic activity. However, the molecular mechanisms
      underlying this effect have not been fully understood. The present study aimed to
      investigate the role of DHA on endothelial cell proliferation, the essential
      process in angiogenesis. Human umbilical vein endothelial cells (HUVECs) treated
      with DHA were examined for proliferation, apoptosis and activation of the
      extracellular signal-regulated kinase (ERK) signaling pathway. Proliferation of
      HUVECs was inhibited by 20 uM DHA without induction of apoptosis. DHA also
      reduced the phosphorylation of ERK1/2, and downregulated the mRNA and protein
      expression of ERK1/2 in HUVECs. In addition, DHA suppressed the transcription and
      protein expression of ERK1/2 downstream effectors c-Fos and c-Myc. Electrical
      cell-substrate impedance sensing real-time analysis demonstrated that ERK
      signaling inhibitor PD98059 comprises the anti-proliferative effects of DHA.
      Thus, DHA inhibits endothelial cell proliferation by suppressing the ERK
      signaling pathway. The present study strengthened the potential of DHA as an
      angiogenesis inhibitor for cancer treatment.

PMID- 25778669
TI  - The Creation and Implementation of a Wellness Initiative in a Large Adult
      Psychiatry Residency Program.

PMID- 25778670
TI  - General and Child and Adolescent Psychiatry Resident Training in Integrated Care:
      a Survey of Program Directors.
AB  - OBJECTIVE: Integrated care models are an evidence-based approach for integrating
      physical and behavioral health services. The American Association of Directors of
      Psychiatric Residency Training Integrated Care Task Force sought to describe
      current practices for providing training in integrated care to general and child
      and adolescent psychiatry residents. METHODS: Directors of US general and child
      and adolescent psychiatric residency training programs were anonymously surveyed
      to examine current practices in educating their residents in integrated care.
      Based on themes that emerged from the survey, the authors make recommendations
      for integrated care education of general and child and adolescent psychiatry
      residents. RESULTS: Fifty-two of 197 (26%) general and 36 of 111 (32%) child and
      adolescent program directors responded. Results demonstrate that a majority of
      responding general psychiatry (78%) and child and adolescent psychiatry (CAP)
      (72%) training programs offer integrated care rotations, many of which are
      electives for senior residents. The Veterans Health Administration (VA) and
      Federally Qualified Health Centers are common venues for such rotations.
      Sustainable funding of these rotations is a concern. Fewer than half of programs
      offer integrated care didactics. CONCLUSIONS: This report is intended to help
      program directors consider options for starting or optimizing their own
      integrated care curricula. Future research should examine the educational value,
      and the overall value to health care systems, of training in the integrated care
      model.

PMID- 25778671
TI  - Deformity of the earlobe caused by fixed cutaneous sporotrichosis in a pediatric
      patient.

PMID- 25778672
TI  - Multistage adaptive biomarker-directed targeted design for randomized clinical
      trials.
AB  - BACKGROUND: Precision medicine is changing how patients are treated and how
      therapies are developed. In recent years, biomarker-directed targeted designs
      have been developed for pharmaceutical development aimed at patient subpopulation
      with a specific disease etiology. To integrate multistage testing into the
      targeted designs enhances flexibility of targeted trials by enabling sequential
      monitoring and stochastic curtailment. METHODS AND RESULTS: We studied a
      multistage adaptive design for targeted trials with either normally distributed
      endpoint or binary endpoint. The design is based on the fact that distribution of
      the sequence of test statistics from multistage testing is asymptotically well
      approximated by a Brownian motion in targeted trials with normally distributed
      continuous endpoint or binary endpoint. This study has demonstrated that the
      targeted multistage design improves study efficiency, information accumulation
      and conditional power as compared with its untargeted counterpart. Furthermore,
      our study has indicated that biomarker performance plays a crucial role in
      efficiency and effectiveness of the multistage adaptive design. The sensitivity
      and specificity of a biomarker used for patient enrichment influence level of
      heterogeneity of the targeted study population, and subsequently impact overall
      trial efficiency and statistical power as well as information accruement and
      conditional/predictive power for stochastic curtailment. When performance of a
      biomarker is imperfect, conditional/predictive power at an earlier stage may be
      over-estimated, resulting invalid early stopping decision. Thus, great care is
      needed to ensure that biomarker performance is considered in statistical planning
      of the multistage targeted trials. CONCLUSIONS: In summary, the multistage
      adaptive design provides targeted trials with flexibility in multistage testing
      and early stopping while retaining the rigor of the study design.

PMID- 25778673
TI  - Construction of giant branched nanotubes from cyclodextrin-based supramolecular
      amphiphiles.
AB  - Giant branched nanotubes were successfully constructed using cyclodextrin-based
      amphiphiles. The 'backbone' of the nanotubes could branch out into two or
      multiple branches, from which thinner branches grow out. 

PMID- 25778674
TI  - Attachment-based family therapy for depressed and suicidal adolescents: theory,
      clinical model and empirical support.
AB  - Attachment-Based Family Therapy (ABFT) is a manualized family-based intervention
      designed for working with depressed adolescents, including those at risk for
      suicide, and their families. It is an empirically informed and supported
      treatment. ABFT has its theoretical underpinnings in attachment theory and
      clinical roots in structural family therapy and emotion focused therapies. ABFT
      relies on a transactional model that aims to transform the quality of adolescent
      parent attachment, as a means of providing the adolescent with a more secure
      relationship that can support them during challenging times generally, and the
      crises related to suicidal thinking and behavior, specifically. This article
      reviews: (1) the theoretical foundations of ABFT (attachment theory, models of
      emotional development); (2) the ABFT clinical model, including training and
      supervision factors; and (3) empirical support. 

PMID- 25778675
TI  - Lactotrophs: the new and major source for VEGF secretion and the influence of ECM
      on rat pituitary function in vitro.
AB  - Vascular endothelial growth factor (VEGF) plays a pivotal role in pituitary
      endocrine function by influencing fenestration and blood vessel growth.
      Folliculostellate (FS) cells, which represent only a small number of pituitary
      cells, are recognized to produce VEGF. Tissue sections and primary pituitary cell
      cultures from rat pituitary glands were performed to co-localize VEGF and
      pituitary lactotrophs, which represents nearly 50% of all pituitary cells, by
      immunofluorescence. VEGF is co-localized with prolactin-producing cells in vivo
      and in vitro. FS cells are present infrequently in vivo (1.6%) and in vitro
      (2.4%). Culture supernatants were analyzed for the presence of VEGF by ELISA.
      VEGF levels are always significantly lower in supernatants from the cells that
      are seeded on Matrigel extracellular matrix (ECM) compared to the cells grown on
      plastic. Lower VEGF concentrations in supernatants from the pituitary cells
      cultured on ECM may reflect a more adequate cell environment compared to culture
      on plastic. These results demonstrate for the first time, that VEGF is expressed
      by lactotrophs, which outnumber FS cells. These results are of potential clinical
      relevance especially in oncology for the interpretation of studies investigating
      anti-angiogenic treatment of pituitary tumors.

PMID- 25778677
TI  - Flagellar kinematics and swimming of algal cells in viscoelastic fluids.
AB  - The motility of microorganisms is influenced greatly by their hydrodynamic
      interactions with the fluidic environment they inhabit. We show by direct
      experimental observation of the bi-flagellated alga Chlamydomonas reinhardtii
      that fluid elasticity and viscosity strongly influence the beating pattern - the
      gait - and thereby control the propulsion speed. The beating frequency and the
      wave speed characterizing the cyclical bending are both enhanced by fluid
      elasticity. Despite these enhancements, the net swimming speed of the alga is
      hindered for fluids that are sufficiently elastic. The origin of this complex
      response lies in the interplay between the elasticity-induced changes in the
      spatial and temporal aspects of the flagellar cycle and the buildup and
      subsequent relaxation of elastic stresses during the power and recovery strokes. 

PMID- 25778678
TI  - HLA high-resolution typing for sensitized patients: a solution in search of a
      problem?

PMID- 25778680
TI  - Impact of dehulling on the physico-chemical properties and in vitro protein
      digestion of common beans (Phaseolus vulgaris L.).
AB  - The objective of this study was to understand the effect of dehulling on the
      microstructural, physico-chemical characteristics, and in vitro protein digestion
      of common bean flours with particular regard to differences between adults and
      infants. The microstructure of flour samples from undehulled (WB) and manually
      dehulled (SB) beans, observed through scanning electron microscopy, showed that
      WB starch granules appeared to be surrounded by an integral matrix, while the SB
      starch granule structure was still visible although covered by protein clusters.
      The starch granules were oval and spherical, with heterogeneous sizes ranging
      from 19 to 30 MUm in diameter. Particle size analysis determined with a laser
      diffraction particle size analyzer showed similar bimodal particle size
      distributions of small (1-25 MUm) and large (>100 MUm) granules, though the
      particle size of WB was obviously higher than SB. Color and other physico
      chemical analyses showed that dehulling had significant (P < 0.05) influence on
      all investigated characteristics. The in vitro gastric and duodenal digestion
      experiments carried out under physiological conditions showed that the SB samples
      are more likely to be digested by infants. From our results, it is possible to
      conclude that the dehulling process improves bean flour protein digestion which
      could be utilized in various food applications. 

PMID- 25778676
TI  - Degradation of the endothelial glycocalyx in clinical settings: searching for the
      sheddases.
AB  - The endothelial glycocalyx has a profound influence at the vascular wall on the
      transmission of shear stress, on the maintenance of a selective permeability
      barrier and a low hydraulic conductivity, and on attenuating firm adhesion of
      blood leukocytes and platelets. Major constituents of the glycocalyx, including
      syndecans, heparan sulphates and hyaluronan, are shed from the endothelial
      surface under various acute and chronic clinical conditions, the best
      characterized being ischaemia and hypoxia, sepsis and inflammation,
      atherosclerosis, diabetes, renal disease and haemorrhagic viral infections.
      Damage has also been detected by in vivo microscopic techniques. Matrix
      metalloproteases may shed syndecans and heparanase, released from activated mast
      cells, cleaves heparan sulphates from core proteins. According to new data, not
      only hyaluronidase but also the serine proteases thrombin, elastase, proteinase 3
      and plasminogen, as well as cathepsin B lead to loss of hyaluronan from the
      endothelial surface layer, suggesting a wide array of potentially destructive
      conditions. Appropriately, pharmacological agents such as inhibitors of
      inflammation, antithrombin and inhibitors of metalloproteases display potential
      to attenuate shedding of the glycocalyx in various experimental models. Also,
      plasma components, especially albumin, stabilize the glycocalyx and contribute to
      the endothelial surface layer. Though symptoms of the above listed diseases and
      conditions correlate with sequelae expected from disturbance of the endothelial
      glycocalyx (oedema, inflammation, leukocyte and platelet adhesion, low reflow),
      therapeutic studies to prove a causal connection have yet to be designed. With
      respect to studies on humans, some clinical evidence exists for benefits from
      application of sulodexide, a preparation delivering precursors of the glycocalyx
      constituent heparan sulphate. At present, the simplest option for protecting the
      glycocalyx seems to be to ensure an adequate level of albumin. However, also in
      this case, definite proof of causality needs to be delivered. 

PMID- 25778681
TI  - The triple threat of HIV-1 protease inhibitors.
AB  - Newly released human immunodeficiency virus type 1 (HIV-1) particles obligatorily
      undergo a maturation process to become infectious. The HIV-1 protease (PR)
      initiates this step, catalyzing the cleavage of the Gag and Gag-Pro-Pol
      structural polyproteins. Proper organization of the mature virus core requires
      that cleavage of these polyprotein substrates proceeds in a highly regulated,
      specific series of events. The vital role the HIV-1 PR plays in the viral life
      cycle has made it an extremely attractive target for inhibition and has
      accordingly fostered the development of a number of highly potent substrate
      analog inhibitors. Though the PR inhibitors (PIs) inhibit only the HIV-1 PR,
      their effects manifest at multiple different stages in the life cycle due to the
      critical importance of the PR in preparing the virus for these subsequent events.
      Effectively, PIs masquerade as entry inhibitors, reverse transcription
      inhibitors, and potentially even inhibitors of post-reverse transcription steps.
      In this chapter, we review the triple threat of PIs: the intermolecular
      cooperativity in the form of a cooperative dose-response for inhibition in which
      the apparent potency increases with increasing inhibition; the pleiotropic
      effects of HIV-1 PR inhibition on entry, reverse transcription, and post-reverse
      transcription steps; and their potency as transition state analogs that have the
      potential for further improvement that could lead to an inability of the virus to
      evolve resistance in the context of single drug therapy. 

PMID- 25778684
TI  - The critical importance of gap modes in surface enhanced Raman scattering.
AB  - For efficient utilization of surface plasmons in surface enhanced Raman
      scattering (SERS), we investigated the gap modes in flocculates of metal
      nanoparticles (MNPs), and between MNPs and metal substrates under an external and
      an attenuated total reflection (ATR) geometry. First, the adsorbed state of thiol
      molecules and counter ions trapped in solutions were elucidated using
      flocculation-SERS, in which closely adjacent nanoparticles are formed by using
      interactions between MNPs and target species. Second, we obtained a pronounced
      enhancement of 10(5)-10(8) at a nanogap between gold nanoparticles (AuNPs) and
      various metal substrates even with a large damping under an external geometry.
      Markedly larger enhancement was obtained for larger AuNPs, by a factor of 10(3)
      for particles with a radius (r) of 50 nm compared with those of r=15 nm in this
      geometry. Finally, we attained an additional enhancement factor under an ATR
      geometry by a coupling of propagating surface plasmons with gap modes.

PMID- 25778683
TI  - Analysis of the microRNA expression profile of normal human dermal papilla cells
      treated with 5alpha-dihydrotestosterone.
AB  - Clinical evidence has demonstrated that the accumulation of 5alpha
      dihydrotestosterone (DHT) in dermal papilla cells (DPCs) is implicated in
      androgenetic alopecia. Whether this accumulation in DHT may have direct cellular
      effects leading to androgenetic alopecia remains to be elucidated. The present
      study aimed to determine whether DHT affects cell growth, cell cycle arrest, cell
      death, senescence and the induction of reactive oxygen species (ROS), and whether
      these effects are mediated by microRNA (miRNA)-dependent mechanisms. The cell
      viability and cell cycle were determined, levels of ROS were examined and
      senescence-associated beta-galactosidase assays were performed in normal human
      DPCs (nHDPCs). Furthermore, miRNA expression profiling was performed using an
      miRNA microarray to determine whether changes in the expression levels of miRNA
      were associated with the cellular effects of DHT. The results revealed that DHT
      decreased cell growth by inducing cell death and G2 cell cycle arrest, and by
      increasing the production of ROS and senescence in the nHDPCs. In addition, 55
      miRNAs were upregulated and 6 miRNAs were downregulated in the DHT-treated
      nHDPCs. Bioinformatic analysis demonstrated that the putative target genes of
      these upregulated and downregulated miRNAs were involved in cell growth, cell
      cycle arrest, cell death, senescence and the production of ROS. Specifically, the
      target genes of five highly upregulated and downregulated miRNAs were identified
      and were associated with the aforementioned effects of DHT. These results
      demonstrated that the expression of miRNA was altered in the DHT-treated nHDPCs
      and suggest the potential mechanisms of DHT-induced cell growth repression, cell
      cycle arrest, cell death, senescence and induction of ROS.

PMID- 25778682
TI  - HIV-1 integrase multimerization as a therapeutic target.
AB  - Multimeric HIV-1 integrase (IN) plays an essential, multifunctional role in virus
      replication and serves as an important therapeutic target. Structural and
      biochemical studies have revealed the importance of the ordered interplay between
      IN molecules for its function. In the presence of viral DNA ends, individual IN
      subunits assemble into a tetramer and form a stable synaptic complex (SSC), which
      mediates integration of the reverse transcribed HIV-1 genome into chromatin.
      Cellular chromatin-associated protein LEDGF/p75 engages the IN tetramer in the
      SSC and directs HIV-1 integration into active genes. A mechanism to deregulate
      the productive interplay between IN subunits with small molecule inhibitors has
      recently received considerable attention. Most notably, allosteric IN inhibitors
      (ALLINIs) have been shown to bind to the IN dimer interface at the LEDGF/p75
      binding pocket, stabilize interacting IN subunits, and promote aberrant, higher
      order IN multimerization. Consequently, these compounds impair formation of the
      SSC and associated LEDGF/p75-independent IN catalytic activities as well as
      inhibit LEDGF/p75 binding to the SSC in vitro. However, in infected cells,
      ALLINIs more potently impaired correct maturation of virus particles than the
      integration step. ALLINI treatments induced aberrant, higher order IN
      multimerization in virions and resulted in eccentric, non-infectious virus
      particles. These studies have suggested that the correctly ordered IN structure
      is important for virus particle morphogenesis and highlighted IN multimerization
      as a plausible therapeutic target for developing new inhibitors to enhance
      treatment options for HIV-1-infected patients. 

PMID- 25778685
TI  - Randomized study comparing vitamin D3 and 1alpha-Hydroxyvitamin D3 in combination
      with pegylated interferon/ribavirin therapy for chronic hepatitis C.
AB  - BACKGROUND AND AIM: An intention-to-treat prospective randomized study was
      carried out to compare the potentiation of antiviral efficacies between
      cholecalciferol, non-activated vitamin D3 supplement, and alfacalcidol, activated
      1alpha-Hydroxyvitamin D3 [1alpha (OH)-vitamin D3]. METHODS: Chronic hepatitis
      patients with genotype 1b hepatitis C virus (HCV) infection showing serum HCV-RNA
      levels greater than 5 Log IU/mL received oral administration of cholecalciferol
      (2000 IU/day) or alfacalcidol (0.5 MUg/day) for 4 weeks, and then they were given
      pegylated interferon (Peg-IFN)-alpha2a plus ribavirin therapy in combination with
      either vitamin D3 for 48 or 72 weeks according to the response-guided manner.
      RESULTS: A total of 36 patients were evaluated. Serum 25-hydroxyvitamin D3
      [25(OH)-D3] levels were increased only in patients in the cholecalciferol group
      during the lead-in vitamin D administration, and the levels at 4 weeks were
      higher in these patients than in those in the alfacalcidol group (P < 0.001),
      while serum 1alpha,25-dihydroxyvitamin D3 [1alpha,25(OH)2 -D3] levels were not
      different between both groups. Rapid virological response was obtained in six
      (33%) patients in the cholecalciferol group; the ratio was higher than that in
      the alfacalcidol group (one patient; 6%, P < 0.05). Serum HCV-RNA level decline
      at 4 weeks of combined Peg-IFN-alpha2a plus ribavirin therapy compared with the
      baseline levels were greater in the cholecalciferol group (4.6 Log IU/mL) than in
      the alfacalcidol group (3.5 Log IU/mL) (P < 0.05), when four patients showing
      null response to the therapy was excluded. However, both complete early
      virological response and sustained viral response rates were not different
      between both groups. CONCLUSION: Cholecalciferol produced superior potentiation
      of the antiviral activity than alfacalcidol only during the initial periods of
      combined Peg-IFN-alpha2a plus ribavirin therapy through upregulation of serum
      25(OH)-D3 levels.

PMID- 25778686
TI  - A Comprehensive Assessment of the Value of Laboratory Indices in Diagnosing
      Kawasaki Disease.
AB  - OBJECTIVE: Kawasaki disease (KD) is the primary cause of heart disease among
      children, but because its clinical symptoms are nonspecific, it is difficult to
      diagnose. The purpose of this study was to evaluate laboratory indices for
      possible use in the early diagnosis of KD and to determine which indices are
      predictive of a response to intravenous immunoglobulin (IVIG) and can be used to
      monitor the effects of treatment. METHODS: Three hundred thirty KD patients, 330
      age-matched children with KD-like febrile disease, and 330 age-matched healthy
      children (controls) were enrolled in this prospective study. Levels of N-terminal
      pro-brain natriuretic peptide (NT-proBNP), erythrocyte sedimentation rate (ESR),
      C-reactive protein (CRP), and cytokines were determined in all study subjects.
      RESULTS: In the derivation cohort, 181 patients in the KD group were compared
      with 181 patients in the KD-like febrile group. The following indices were found
      to be useful in the diagnosis of KD: NT-proBNP (area under the curve [AUC]
      0.923), ESR (AUC 0.909), CRP (AUC 0.834), and interleukin-6 (IL-6; AUC 0.678).
      The diagnostic efficiency of each index demonstrated in the derivation cohort was
      repeated in the 149 KD patients in the validation cohort. There were significant
      differences in NT-proBNP levels between IVIG-responsive KD patients (n = 270) and
      IVIG-nonresponsive KD patients (n = 60), with higher NT-proBNP levels in IVIG
      nonresponsive KD patients. The NT-proBNP level can effectively distinguish IVIG
      responsive KD patients from IVIG-nonresponsive patients, and its AUC was 0.73.
      There were also significant differences in the NT-proBNP levels before and after
      treatment, with a significant decline after treatment. CONCLUSION: Serum levels
      of NT-proBNP can be used in the diagnosis of KD, the prediction of a patient's
      sensitivity to IVIG treatment, and the monitoring of the effects of IVIG
      treatment, but more attention must be paid to the scope of its application.

PMID- 25778687
TI  - Hospital Volume Does Not Influence the Safety of Percutaneous Nephrolithotomy in
      England: A Population-Based Cohort Study.
AB  - PURPOSE: This study aims to investigate the relationship between hospital case
      volume and safety-related outcomes after percutaneous nephrolithotomy (PCNL)
      within the English National Health Service (NHS). PATIENTS AND METHODS: The study
      used the Hospital Episode Statistics (HES) database, a routine administrative
      database, recording information on operations, comorbidity, and outcomes for all
      NHS hospital admissions in England. Records for all patients undergoing an
      initial PCNL between April 1, 2006 and March 31, 2012 were extracted. NHS trusts
      were divided into low-, medium-, and high-volume groups, according to the average
      annual number of PCNLs performed. We used multiple regression analyses to examine
      the associations between hospital volume and outcomes incorporating risk
      adjustment for sex, age, comorbidity, and hospital teaching status. Postoperative
      outcomes included: Emergency readmission, infection, and hemorrhage. Mean length
      of stay was also measured. RESULTS: There were 7661 index elective PCNL
      procedures performed in 163 hospital trusts, between April 2006 and March 2012.
      There were 2459 patients who underwent PCNL in the 116 units performing fewer
      than 10 PCNL procedures per year; 2643 patients in the 37 units performing 10 to
      19 procedures per year; and 2459 patients in the 9 hospitals performing more than
      20 procedures per year. For low-, medium-, and high-volume trusts, there was
      little variation in the rates of emergency readmission (L 9.7%, M 9.3%, H 8.4%),
      infection (3.0%, 4.2%, 3.8%), or hemorrhage (1.3%, 1.5%, 1.5%), and there was no
      statistical evidence that volume was associated with adjusted outcomes. Mean
      length of stay was slightly shorter in the medium- (5.0 days) and high-volume
      (5.0) groups compared with the low-volume group (5.3). The effect remained
      statistically significant after adjusted for confounding. CONCLUSION: Hospital
      volume was not associated with emergency readmission, infection, or hemorrhage.
      Length of stay appears to be shorter in higher volume units.

PMID- 25778688
TI  - Aflatoxin B1 is toxic to porcine oocyte maturation.
AB  - As a toxic secondary metabolite of Aspergillus species, Aflatoxin B1 (AFB1) is a
      major food and feed contaminant in tropical and sub-tropical regions with high
      temperature and humidity. It has been reported to be toxic to the female
      reproductive system in laboratory and domestic animals. In the present study, the
      influence of acute exposure to AFB1 (10 and 50 MUM, 44h) on porcine oocyte
      maturation and its possible mechanism were investigated. The maturation rates of
      oocytes decreased significantly in the presence of 50 MUM of AFB1. Cell cycle
      analysis showed that most oocytes were arrested at germinal vesicle breakdown or
      meosis I stage. However, actin assembly, spindle structure and chromosome
      alignment were not disrupted after exposure to 50 MUM AFB1. Further study showed
      that DNA methylation levels increased in treated oocytes (50 MUM). Histone
      methylation levels were also analysed after treatment (50 MUM): H3K27me3 and
      H3K4me2 levels decreased, whereas H3K9me3 level increased, indicating that
      epigenetic modification was affected. AFB1 treatment (50 MUM) also induced
      oxidative stress and further led to autophagy, as shown by accumulation of
      reactive oxygen species, up-regulated LC3 protein expression and increased mRNA
      levels of ATG3, ATG5 and ATG7. Annexin V-FITC staining assay revealed that AFB1
      treatment (50 MUM) resulted in oocyte early apoptosis, which was confirmed by
      increased Bak, Bax, Bcl-xl mRNA levels. Collectively, our results suggest that
      AFB1 disrupts porcine oocyte maturation through changing epigenetic modifications
      as well as inducing oxidative stress, excessive autophagy and apoptosis. 

PMID- 25778690
TI  - Enhancing our understanding of perinatal depression.

PMID- 25778689
TI  - Prevention of myelosuppression and genotoxicity induced by cisplatin in murine
      bone marrow cells: effect of an organovanadium compound vanadium(III)-l-cysteine.
AB  - Cisplatin (CDDP) is one of the first-line anticancer drugs indicated for use
      against various form of human malignancies; but, the therapeutic outcome of CDDP
      chemotherapy is limited due to the development of myelosuppression and
      genotoxicity which may lead to secondary cancer. Induction of oxidative stress in
      normal host cells is thought to be responsible for these adverse effects.
      Therefore, in search of a potential chemoprotectant, an oraganovanadium compound,
      viz., vanadium(III)-l-cysteine (VC-III) was evaluated against CDDP-induced
      clastogenicity and cytotoxicity in bone marrow cells of Swiss albino mice. CDDP
      was administered intraperitoneally (5mg/kg body weight [b.w.]) and VC-III was
      given by oral gavage (1mg/kg b.w.) in concomitant and pretreatment schedule. The
      results showed that VC-III administration significantly (P < 0.001) enhanced cell
      proliferation and inhibited apoptosis in the bone marrow niche indicating
      recovery of CDDP-induced myelosuppression. VC-III also significantly (P < 0.001)
      decreased the percentage of chromosomal aberrations, the frequency of micronuclei
      formation and the extent of DNA damage. The observed antigenotoxic and
      cytoprotective effect of VC-III was attributed to its attenuation of free
      radicals status and restoration of oxidised and reduced glutathione levels. These
      results suggest that VC-III is a potential candidate for future development as a
      chemoprotective agent against chemotherapy-associated primary and secondary
      complications. 

PMID- 25778691
TI  - Antidepressant medication use, depression, and the risk of preeclampsia.
AB  - OBJECTIVE: To assess the effects of depression and antidepressant medication use
      during pregnancy on the risk of preeclampsia. METHODS: We conducted a
      retrospective, population-based cohort study that linked automated clinical and
      pharmacy databases including comprehensive electronic medical records of 21,589
      pregnant Kaiser Permanente Northern California members between 2010 and 2012.
      RESULTS: The overall risk of preeclampsia was 4.5%. The timing of antidepressant
      medication exposure was an important factor. A significant increase in the risk
      of preeclampsia emerged for women with a depression diagnosis who took
      antidepressant medications during the second trimester compared to women with
      untreated depression (adjusted relative risk [aRR]: 1.6, 95% CI: 1.06, 2.39) and
      to women without depression (aRR: 1.70, 95% CI: 1.30, 2.23). Similar associations
      existed for women who took antidepressant medications, but without depression. In
      contrast, depressed women with psychotherapy showed no increased risk of
      preeclampsia compared to women with untreated depression or no depression. There
      was also a statistically significant relationship between the duration of
      antidepressant medication use and preeclampsia. The observed association appeared
      stronger for selective serotonin reuptake inhibitor (SSRI) use, although a
      nonsignificant trend was also noted for use of norepinephrine-dopamine reuptake
      inhibitors (NDRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs).
      CONCLUSION: Study findings suggest that antidepressant use during pregnancy may
      increase the risk of preeclampsia, especially use during the second trimester.

PMID- 25778692
TI  - Ruthenium polypyridyl complex inhibits growth and metastasis of breast cancer
      cells by suppressing FAK signaling with enhancement of TRAIL-induced apoptosis.
AB  - Ruthenium-based complexes have emerged as promising antitumor and antimetastatic
      agents during the past decades. However, the limited understanding of the
      antimetastatic mechanisms of these agents is a roadblock to their clinical
      application. Herein, we reported that, RuPOP, a ruthenium polypyridyl complex
      with potent antitumor activity, was able to effectively inhibit growth and
      metastasis of MDA-MB-231 cells and synergistically enhance TRAIL-induced
      apoptosis. The selective intracellular uptake and cytotoxic effect of RuPOP was
      found associated with transferring receptor (TfR)-mediated endocytosis. Further
      investigation on intracellular mechanisms reveled that RuPOP notably suppressed
      FAK-mediated ERK and Akt activation. Pretreatment of cells with ERK inhibitor
      (U0126) and PI3K inhibitor (LY294002) significantly potentiated the inhibitory
      effect of RuPOP on cell growth, migration and invasion. Moreover, the alternation
      in the expression levels of metastatic regulatory proteins, including uPA, MMP-2/
      9, and inhibition of VEGF secretion were also observed after RuPOP treatment.
      These results demonstrate the inhibitory effect of RuPOP on the growth and
      metastasis of cancer cells and the enhancement of TRAIL-induced apoptosis though
      suppression of FAK-mediated signaling. Furthermore, RuPOP exhibits the potential
      to be developed as a metal-based antimetastatic agent and chemosensitizer of
      TRAIL for the treatment of human metastatic cancers. 

PMID- 25778693
TI  - Microcystin-LR Alters the Gene Transcription and Activities of Iodothyronine
      Deiodinases in the Hepatic Cells of Grass Carp (Ctenopharyngodon Idella).
AB  - This study investigated the gene transcription and activities of iodothyronine
      deiodinases in the hepatic cell line of grass carp (Ctenopharyngodon idella)
      exposed in vitro to 1, 10, 100, and 1000 MUg /L microcystin-LR (MC-LR) for either
      24 or 48 h. The cell viabilities were not significantly affected by MC-LR
      exposure. The mRNA expressions of type I iodothyronine deiodinase (ID1) and type
      II iodothyronine deiodinase (ID2) reduced after the exposure to MC-LR. However,
      MC-LR exposure led to the increase in the mRNA expression of type III
      iodothyronine deiodinase (ID3). Moreover, significant ID1 and ID2 activities
      decline were also observed in the hepatic cell line of grass carp exposed to MC
      LR, and the activity of ID3 increased significantly in the MC-LR treated groups.
      The results suggested that MC-LR could alter the gene transcription or activities
      of IDs in the hepatic cell line of grass carp. 

PMID- 25778694
TI  - Confluence, synnovation, and depauperons in plant diversification.
AB  - We review the empirical phylogenetic literature on plant diversification,
      highlighting challenges in separating the effects of speciation and extinction,
      in specifying diversification mechanisms, and in making convincing arguments. In
      recent discussions of context dependence, key opportunities and landscapes, and
      indirect effects and lag times, we see a distinct shift away from single
      point/single-cause 'key innovation' hypotheses toward more nuanced explanations
      involving multiple interacting causal agents assembled step-wise through a tree.
      To help crystalize this emerging perspective we introduce the term 'synnovation'
      (a hybrid of 'synergy' and 'innovation') for an interacting combination of traits
      with a particular consequence ('key synnovation' in the case of increased
      diversification rate), and the term 'confluence' for the sequential coming
      together of a set of traits (innovations and synnovations), environmental
      changes, and geographic movements along the branches of a phylogenetic tree. We
      illustrate these concepts using the radiation of Bromeliaceae. We also highlight
      the generality of these ideas by considering how rate heterogeneity associated
      with a confluence relates to the existence of particularly species-poor lineages,
      or 'depauperons.' Many challenges are posed by this re-purposed research
      framework, including difficulties associated with partial taxon sampling,
      uncertainty in divergence time estimation, and extinction.

PMID- 25778695
TI  - A simple method for positive pressure ventilation during fibreoptic intubation.

PMID- 25778696
TI  - Is anatomic complexity associated with renal tumor growth kinetics under active
      surveillance?
AB  - INTRODUCTION: Linear growth rate (LGR) is the most commonly employed trigger for
      definitive intervention in patients with renal masses managed with an initial
      period of active surveillance (AS). Using our institutional cohort, we explored
      the association between tumor anatomic complexity at presentation and LGR in
      patients managed with AS. METHODS AND MATERIALS: Enhancing renal masses managed
      expectantly for at least 6 months were included for analysis. The association
      between Nephrometry Score and LGR was assessed using generalized estimating
      equations, adjusting for the age, Charlson score, race, sex, and initial tumor
      size. RESULTS: Overall, 346 patients (401 masses) met the inclusion criteria (18%
      >= cT1b), with a median follow-up of 37 months (range: 6-169). Of these, 44%
      patients showed progression to definitive intervention with a median duration of
      27 months (range: 6-130). On comparing patients managed expectantly to those
      requiring intervention, no difference was seen in median tumor size at
      presentation (2.2 vs. 2.2 cm), whereas significant differences in median age (74
      vs. 65 y, P < 0.001), Charlson comorbidity score (3 vs. 2, P<0.001), and average
      LGR (0.23 vs. 0.49 cm/y, P < 0.001) were observed between groups. Following
      adjustment, for each 1-point increase in Nephrometry Score sum, the average tumor
      LGR increased by 0.037 cm/y (P = 0.002). Of the entire cohort, 6 patients (1.7%)
      showed progression to metastatic disease. CONCLUSIONS: The demonstrated
      association between anatomic tumor complexity at presentation and renal masses of
      LGR of clinical stage 1 under AS may afford a clinically useful cue to tailor
      individual patient radiographic surveillance schedules and warrants further
      evaluation.

PMID- 25778697
TI  - Should we systematically test patients with clinically isolated syndrome for auto
      antibodies?
AB  - BACKGROUND: Several autoimmune diseases (ADs) can mimic multiple sclerosis (MS).
      For this reason, testing for auto-antibodies (auto-Abs) is often included in the
      diagnostic work-up of patients with a clinically isolated syndrome (CIS).
      OBJECTIVE: The purpose was to study how useful it was to systematically determine
      antinuclear-antibodies, anti-SSA and anti-SSB in a non-selected cohort of CIS
      patients, regarding the identification of other ADs that could represent an
      alternative diagnosis. METHODS: From a prospective CIS cohort, we selected 772
      patients in which auto-Ab levels were tested within the first year from CIS.
      Baseline characteristics of auto-Ab positive and negative patients were compared.
      A retrospective revision of clinical records was then performed in the auto-Ab
      positive patients to identify those who developed ADs during follow-up. RESULTS:
      One or more auto-Ab were present in 29.4% of patients. Only 1.8% of patients
      developed other ADs during a mean follow-up of 6.6 years. In none of these cases
      the concurrent AD was considered the cause of the CIS. In all cases the diagnosis
      of the AD resulted from the development of signs and/or symptoms suggestive of
      each disease. CONCLUSION: Antinuclear-antibodies, anti-SSA and anti-SSB should
      not be routinely determined in CIS patients but only in those presenting symptoms
      suggestive of other ADs.

PMID- 25778700
TI  - Atomic structure of anthrax protective antigen pore elucidates toxin
      translocation.
AB  - Anthrax toxin, comprising protective antigen, lethal factor, and oedema factor,
      is the major virulence factor of Bacillus anthracis, an agent that causes high
      mortality in humans and animals. Protective antigen forms oligomeric prepores
      that undergo conversion to membrane-spanning pores by endosomal acidification,
      and these pores translocate the enzymes lethal factor and oedema factor into the
      cytosol of target cells. Protective antigen is not only a vaccine component and
      therapeutic target for anthrax infections but also an excellent model system for
      understanding the mechanism of protein translocation. On the basis of biochemical
      and electrophysiological results, researchers have proposed that a phi (Phi)
      clamp composed of phenylalanine (Phe)427 residues of protective antigen catalyses
      protein translocation via a charge-state-dependent Brownian ratchet. Although
      atomic structures of protective antigen prepores are available, how protective
      antigen senses low pH, converts to active pore, and translocates lethal factor
      and oedema factor are not well defined without an atomic model of its pore. Here,
      by cryo-electron microscopy with direct electron counting, we determine the
      protective antigen pore structure at 2.9-A resolution. The structure reveals the
      long-sought-after catalytic Phi-clamp and the membrane-spanning translocation
      channel, and supports the Brownian ratchet model for protein translocation.
      Comparisons of four structures reveal conformational changes in prepore to pore
      conversion that support a multi-step mechanism by which low pH is sensed and the
      membrane-spanning channel is formed. 

PMID- 25778701
TI  - Shape-changing magnetic assemblies as high-sensitivity NMR-readable nanoprobes.
AB  - Fluorescent and plasmonic labels and sensors have revolutionized molecular
      biology, helping visualize cellular and biomolecular processes. Increasingly,
      such probes are now being designed to respond to wavelengths in the near-infrared
      region, where reduced tissue autofluorescence and photon attenuation enable
      subsurface in vivo sensing. But even in the near-infrared region, optical
      resolution and sensitivity decrease rapidly with increasing depth. Here we
      present a sensor design that obviates the need for optical addressability by
      operating in the nuclear magnetic resonance (NMR) radio-frequency spectrum, where
      signal attenuation and distortion by tissue and biological media are negligible,
      where background interferences vanish, and where sensors can be spatially located
      using standard magnetic resonance imaging (MRI) equipment. The radio-frequency
      addressable sensor assemblies presented here comprise pairs of magnetic disks
      spaced by swellable hydrogel material; they reversibly reconfigure in rapid
      response to chosen stimuli, to give geometry-dependent, dynamic NMR spectral
      signatures. The sensors can be made from biocompatible materials, are themselves
      detectable down to low concentrations, and offer potential responsive NMR
      spectral shifts that are close to a million times greater than those of
      traditional magnetic resonance spectroscopies. Inherent adaptability should allow
      such shape-changing systems to measure numerous different environmental and
      physiological indicators, thus providing broadly generalizable, MRI-compatible,
      radio-frequency analogues to optically based probes for use in basic chemical,
      biological, medical and engineering research. 

PMID- 25778703
TI  - Monolayer semiconductor nanocavity lasers with ultralow thresholds.
AB  - Engineering the electromagnetic environment of a nanometre-scale light emitter by
      use of a photonic cavity can significantly enhance its spontaneous emission rate,
      through cavity quantum electrodynamics in the Purcell regime. This effect can
      greatly reduce the lasing threshold of the emitter, providing a low-threshold
      laser system with small footprint, low power consumption and ultrafast
      modulation. An ultralow-threshold nanoscale laser has been successfully developed
      by embedding quantum dots into a photonic crystal cavity (PCC). However, several
      challenges impede the practical application of this architecture, including the
      random positions and compositional fluctuations of the dots, extreme difficulty
      in current injection, and lack of compatibility with electronic circuits. Here we
      report a new lasing strategy: an atomically thin crystalline semiconductor--that
      is, a tungsten diselenide monolayer--is non-destructively and deterministically
      introduced as a gain medium at the surface of a pre-fabricated PCC. A continuous
      wave nanolaser operating in the visible regime is thereby achieved with an
      optical pumping threshold as low as 27 nanowatts at 130 kelvin, similar to the
      value achieved in quantum-dot PCC lasers. The key to the lasing action lies in
      the monolayer nature of the gain medium, which confines direct-gap excitons to
      within one nanometre of the PCC surface. The surface-gain geometry gives
      unprecedented accessibility and hence the ability to tailor gain properties via
      external controls such as electrostatic gating and current injection, enabling
      electrically pumped operation. Our scheme is scalable and compatible with
      integrated photonics for on-chip optical communication technologies.

PMID- 25778702
TI  - YAP is essential for tissue tension to ensure vertebrate 3D body shape.
AB  - Vertebrates have a unique 3D body shape in which correct tissue and organ shape
      and alignment are essential for function. For example, vision requires the lens
      to be centred in the eye cup which must in turn be correctly positioned in the
      head. Tissue morphogenesis depends on force generation, force transmission
      through the tissue, and response of tissues and extracellular matrix to force.
      Although a century ago D'Arcy Thompson postulated that terrestrial animal body
      shapes are conditioned by gravity, there has been no animal model directly
      demonstrating how the aforementioned mechano-morphogenetic processes are
      coordinated to generate a body shape that withstands gravity. Here we report a
      unique medaka fish (Oryzias latipes) mutant, hirame (hir), which is sensitive to
      deformation by gravity. hir embryos display a markedly flattened body caused by
      mutation of YAP, a nuclear executor of Hippo signalling that regulates organ
      size. We show that actomyosin-mediated tissue tension is reduced in hir embryos,
      leading to tissue flattening and tissue misalignment, both of which contribute to
      body flattening. By analysing YAP function in 3D spheroids of human cells, we
      identify the Rho GTPase activating protein ARHGAP18 as an effector of YAP in
      controlling tissue tension. Together, these findings reveal a previously
      unrecognised function of YAP in regulating tissue shape and alignment required
      for proper 3D body shape. Understanding this morphogenetic function of YAP could
      facilitate the use of embryonic stem cells to generate complex organs requiring
      correct alignment of multiple tissues. 

PMID- 25778704
TI  - Selection on noise constrains variation in a eukaryotic promoter.
AB  - Genetic variation segregating within a species reflects the combined activities
      of mutation, selection, and genetic drift. In the absence of selection,
      polymorphisms are expected to be a random subset of new mutations; thus,
      comparing the effects of polymorphisms and new mutations provides a test for
      selection. When evidence of selection exists, such comparisons can identify
      properties of mutations that are most likely to persist in natural populations.
      Here we investigate how mutation and selection have shaped variation in a cis
      regulatory sequence controlling gene expression by empirically determining the
      effects of polymorphisms segregating in the TDH3 promoter among 85 strains of
      Saccharomyces cerevisiae and comparing their effects to a distribution of
      mutational effects defined by 236 point mutations in the same promoter.
      Surprisingly, we find that selection on expression noise (that is, variability in
      expression among genetically identical cells) appears to have had a greater
      impact on sequence variation in the TDH3 promoter than selection on mean
      expression level. This is not necessarily because variation in expression noise
      impacts fitness more than variation in mean expression level, but rather because
      of differences in the distributions of mutational effects for these two
      phenotypes. This study shows how systematically examining the effects of new
      mutations can enrich our understanding of evolutionary mechanisms. It also
      provides rare empirical evidence of selection acting on expression noise. 

PMID- 25778705
TI  - Tumor profiling of gastric and esophageal carcinoma reveal different treatment
      options.
AB  - BACKGROUND: NCCN states that chemotherapies for advanced esophageal and gastric
      cancers may be used interchangeably. Biomarkers from gastroesophageal cancer
      patients were interrogated to identify actionable alterations with therapeutic
      implications. METHODS: 666 gastric and 640 esophageal cancer cases referred to
      Caris Life Sciences between 2009 thru 2013 were evaluated. Specific testing was
      performed, which included a combination of sequencing (Sanger, NGS) and protein
      expression (IHC). RESULTS: In the complete cohort (n = 1306), 30 of 45 genes
      tested harbored mutations; highest rates were seen in TP53 (54%), APC (10%),
      SMAD4 (5.9%), KRAS (5.9%), and PIK3CA (5.1%). IHC of TOP2A was high in 76% of
      cases, TOPO1 in 51% and SPARC in 25%; low IHC of ERCC1 was seen in 65%, RRM1 in
      62%, TS in 61% and MGMT in 45%, indicating potential benefit from epirubicin,
      irinotecan, nab-paclitaxel, platinum-based agents, gemcitabine, 5FU/capecitabine
      and temozolomide, respectively. In the HER2+ cohort (n = 88), 50% of patients
      demonstrated possible benefit from a combination of trastuzumab with
      5FU/capecitabine based on concurrent low TS, 53% with irinotecan (high TOPO1),
      63% with cisplatin (low ERCC1) and 55% with gemcitabine (low RRM1). Subgroup
      analysis by tumor origin demonstrated significant differences in actionable
      biomarker profiles with HER2 (13% vs. 4.6%), SPARC (34% vs. 15%), TOP2A (86% vs.
      67%), and TOPO1 (55% vs. 46%) in esophageal and gastric adenocarcinoma cases
      respectively (P < 0.05). CONCLUSION: A comprehensive multiplatform biomarker
      analysis suggested significant biomarker differences between gastric and
      esophageal cancers. These results can assist in the development of future
      clinical trials.

PMID- 25778706
TI  - Mutations in CIZ1 are not a major cause for dystonia in Germany.

PMID- 25778707
TI  - How well do the DSM-5 alcohol use disorder designations map to the ICD-10
      disorders?
AB  - BACKGROUND: The Diagnostic and Statistical Manual of Mental Disorders, 5th
      edition (DSM-5), and the International Statistical Classification of Diseases and
      Related Health Problems, 10th edition (ICD-10), both establish diagnostic
      criteria for alcohol use disorders. The dimensional severity perspective provided
      by the DSM-5 may overlap in important ways but also may diverge from the
      categorical harmful use versus dependence designations presented by the ICD-10.
      It is especially important to consider the convergence of these 2 diagnostic
      approaches as the DSM is widely used by clinicians, but the U.S. Centers for
      Medicare and Medicaid Services has recently required that providers bill for
      services using the ICD-10 designations. METHODS: Data from 6,871 male and 801
      female admissions to a state prison system were used to compare the DSM-5
      severity index for alcohol use disorder to the ICD-10 clinical and research
      formulations for harmful use and dependence. RESULTS: The DSM-5 and the ICD-10
      were highly convergent for the most severe alcohol use disorders and also for
      those who did not receive a diagnosis. Most DSM-5 moderate alcohol use disorder
      cases were classified as dependence cases under both the clinical and research
      ICD criteria. In contrast, there was much more variation in the DSM mild cases.
      These were divided into categories of harmful use or misuse, depending on whether
      the clinical or research ICD criteria were applied. Results were similar among
      male and female inmates. CONCLUSIONS: The DSM-5 and ICD-10 exhibit a high level
      of agreement for cases that would not receive a diagnosis as well as the most
      severe cases. However, there are important distinctions to be made between the 2
      approaches for mild and moderate DSM disorders in addition to harmful use/misuse
      cases in the ICD. The cases influenced by these discrepancies are most likely to
      be affected by recently implemented service provider billing practices.

PMID- 25778708
TI  - Design, synthesis and biological evaluation of novel peptide MC2 analogues from
      Momordica charantia as potential anti-diabetic agents.
AB  - Three series of Momordica charantia (MC)2 analogues were designed, synthesized
      and evaluated for their anti-hyperglycaemic effects. Alanine scanning focusing on
      the peptide MC2 indicated the importance of the residues proline (Pro)(3), serine
      (Ser)(6), isoleucine (Ile)(7) and Ser(10) for anti-hyperglycaemic effects. Among
      the first series of MC2 analogues, peptide I-4 exhibited a better anti
      hyperglycaemic effect and was chosen for further modification. A further two
      series of conformationally constrained analogues were designed by scanning the
      residues Pro(3), Ser(6), Ile(7), and Ser(10) with an i - (i + 2) lactam bridge
      consisting of a glutamic acid-Xaa-lysine (Glu-Xaa-Lys) scaffold and a diproline
      fragment. By screening in normal mice and mice with diabetes mellitus, peptides
      II-1, II-2 and III-3 showed a significant improvement in anti-hyperglycaemic and
      anti-oxidative activities compared with I-4. These data suggest that II-1, II-2
      and III-3 could be candidates for future treatment of diabetes mellitus. 

PMID- 25778709
TI  - LC-MS/MS-based serum proteomics for identification of candidate biomarkers for
      hepatocellular carcinoma.
AB  - Associating changes in protein levels with the onset of cancer has been widely
      investigated to identify clinically relevant diagnostic biomarkers. In the
      present study, we analyzed sera from 205 patients recruited in the United States
      and Egypt for biomarker discovery using label-free proteomic analysis by LC
      MS/MS. We performed untargeted proteomic analysis of sera to identify candidate
      proteins with statistically significant differences between hepatocellular
      carcinoma (HCC) and patients with liver cirrhosis. We further evaluated the
      significance of 101 proteins in sera from the same 205 patients through targeted
      quantitation by MRM on a triple quadrupole mass spectrometer. This led to the
      identification of 21 candidate protein biomarkers that were significantly altered
      in both the United States and Egyptian cohorts. Among the 21 candidates, ten were
      previously reported as HCC-associated proteins (eight exhibiting consistent
      trends with our observation), whereas 11 are new candidates discovered by this
      study. Pathway analysis based on the significant proteins reveals upregulation of
      the complement and coagulation cascades pathway and downregulation of the antigen
      processing and presentation pathway in HCC cases versus patients with liver
      cirrhosis. The results of this study demonstrate the power of combining
      untargeted and targeted quantitation methods for a comprehensive serum proteomic
      analysis, to evaluate changes in protein levels and discover novel diagnostic
      biomarkers. All MS data have been deposited in the ProteomeXchange with
      identifier PXD001171
      (http://proteomecentral.proteomexchange.org/dataset/PXD001171). 

PMID- 25778710
TI  - Reply to: "Sorafenib or (90) Y loaded resin microsphere radioembolization for
      locally-advanced hepatocellular carcinoma, what should we trust?".

PMID- 25778711
TI  - Prevalence of ectopic intrathyroidal thymus in Japan: the Fukushima health
      management survey.
AB  - BACKGROUND: Ectopic intrathyroidal thymus is thought to be a rare entity, often
      discovered incidentally, and is due to aberrant thymic migration during
      embryogenesis. OBJECTIVE: The aim of this study was to determine the prevalence
      of ectopic intrathyroidal thymus in children using ultrasound screening. METHODS:
      This study was cross-sectional and was conducted with the initial preliminary
      survey of the Fukushima Health Management Survey between October 9, 2011, and
      March 31, 2012, after the Fukushima Daiichi Nuclear Power Plant accident. A total
      of 37,816 children were examined in the survey. RESULTS: Diagnostic criteria are
      based on the ultrasonographic appearance of ectopic intrathyroidal thymus, which
      were round, oval, or polygonal hypoechoic or hyperechoic areas, with multiple
      granular and punctate echogenic foci. A total of 375 (0.99%) cases (164 girls)
      with ectopic intrathyroidal thymus were observed. The mean age was 7.0 years
      (range 0-18 years). Ectopic intrathyroidal thymus was located in the right
      (n=180), left (n=178), or bilateral (n=17) thyroid lobes. The incidence of
      ectopic intrathyroidal thymus was inversely correlated with age and body mass
      index. CONCLUSION: The results reflect the prevalence of ectopic intrathyroidal
      thymus using ultrasonography in the general population. Further examination will
      be needed by way of longitudinal follow-up.

PMID- 25778712
TI  - Thermal conversion of methane to formaldehyde promoted by gold in AuNbO3(+)
      cluster cations.
AB  - In addition to generation of a methyl radical, formation of a formaldehyde
      molecule was observed in the thermal reaction of methane with AuNbO3(+)
      heteronuclear oxide cluster cations. The clusters were prepared by laser ablation
      and mass-selected to react with CH4 in an ion-trap reactor under thermal
      collision conditions. The reaction was studied by mass spectrometry and DFT
      calculations. The latter indicated that the gold atom promotes formaldehyde
      formation through transformation of an Au-O bond into an Au-Nb bond during the
      reaction.

PMID- 25778714
TI  - A content analytic comparison of fitspiration and thinspiration websites.
AB  - OBJECTIVE: "Pro-ana" or Thinspiration websites are internet sites that support
      weight loss and eating disorders. Fitspiration websites are a newer type of site
      that supposedly advocates a fit and healthy lifestyle. METHOD: The first 10
      images from a sample of 50 Fitspiration and 50 Thinspiration websites, chosen
      using a standard internet search protocol, were rated on a variety of weight,
      eating, and appearance characteristics. chi(2) analyses were conducted to compare
      website content. RESULTS: Thinspiration sites featured more content related to
      losing weight or fat, praising thinness, showng a thin pose, and providing food
      guilt messages than Fitspiration sites. However, sites did not differ on guilt
      inducing messages regarding weight or the body, fat/weight stigmatization, the
      presence of objectifying phrases, and dieting/restraint messages. Overall, 88% of
      Thinspiration sites and 80% of Fitspiration sites contained one or more of the
      coded variables. DISCUSSION: Prior research has examined Thinspiration websites
      and noted the potentially hazardous messages contained on these sites. This
      content analysis indicates that sites supposedly devoted to healthy pursuits
      (fitness) may also contain thematically similar content.

PMID- 25778715
TI  - IFITM3 rs12252 T>C polymorphism is associated with the risk of severe influenza:
      a meta-analysis.
AB  - The interferon-inducible transmembrane protein 3 (IFITM3), as one of the key
      genes involved in the interferon pathway, is critical for defending the host
      against influenza virus, and the rs12252 T>C variant in IFITM3 might be
      associated with susceptibility to severe influenza. Owing to contradictory and
      inconclusive results, we performed a meta-analysis to assess the association
      between rs12252 T>C polymorphism and severe influenza risk. A comprehensive
      literature search up to 1 August 2014 was conducted in EMBASE, Pubmed, Web of
      Science, VIP, Wanfang and CNKI databases. Four eligible studies with a total of
      445 influenza patients and 3396 controls were included in this meta-analysis.
      Overall, our results demonstrated a significant association between the IFITM3
      rs12252 T>C polymorphism and influenza risk [C vs. T: odds ratio (OR) 1.68, 95%
      confidence interval (CI) 1.32-2.13; CC vs. CT+TT: OR 2.38, 95% CI 1.52-3.73;
      CC+CT vs. TT: OR 1.62, 95% CI 1.18-2.22]. Stratification by ethnicity indicated
      that the variant C allele was associated with an 88% increased risk of influenza
      in Asians (C vs. T: OR 1.88, 95% CI 1.34-2.62). Moreover, subjects carrying the
      variant C allele had an increased risk of developing severe illness upon
      influenza infection (C vs. T: OR 2.70, 95% CI 1.86-3.94). However, no significant
      association was observed in patients with mild infection (C vs. T: OR 1.26, 95%
      CI 0.93-1.71). Our meta-analysis suggests that IFITM3 rs12252 T>C polymorphism is
      significantly associated with increased risk of severe influenza but not with the
      chance of initial virus infection. 

PMID- 25778713
TI  - Generation and Assessment of Functional Biomaterial Scaffolds for Applications in
      Cardiovascular Tissue Engineering and Regenerative Medicine.
AB  - Current clinically applicable tissue and organ replacement therapies are limited
      in the field of cardiovascular regenerative medicine. The available options do
      not regenerate damaged tissues and organs, and, in the majority of the cases,
      show insufficient restoration of tissue function. To date, anticoagulant drug
      free heart valve replacements or growing valves for pediatric patients,
      hemocompatible and thrombus-free vascular substitutes that are smaller than 6 mm,
      and stem cell-recruiting delivery systems that induce myocardial regeneration are
      still only visions of researchers and medical professionals worldwide and far
      from being the standard of clinical treatment. The design of functional off-the
      shelf biomaterials as well as automatable and up-scalable biomaterial processing
      methods are the focus of current research endeavors and of great interest for
      fields of tissue engineering and regenerative medicine. Here, various approaches
      that aim to overcome the current limitations are reviewed, focusing on
      biomaterials design and generation methods for myocardium, heart valves, and
      blood vessels. Furthermore, novel contact- and marker-free biomaterial and
      extracellular matrix assessment methods are highlighted. 

PMID- 25778727
TI  - Calf management practices, challenges and opportunities in traditional cattle
      production systems in the Peanut Basin of Senegal.
AB  - Calf management in traditional cattle herds in many parts of the tropics receive
      less attention as compared to immediate income-generating cows or bulls.
      Information on long-term implications of poorly reared young stock is limited. A
      study to assess practices, challenges and opportunities during rearing of less
      than 12-month-old calves in traditional cattle herds in the Peanut Basin of
      Senegal was carried out. Data were collected on 207 farms through farm visits and
      completion of a questionnaire. Categorical principal component analysis followed
      by two-step cluster analysis identified two cattle production systems: livestock
      based (LB: 47.83 %) and livestock-crop based (LCB, 52.17 %). On average, 2.81 +/-
      0.15 calves were reared per farm. Calves were weaned at the age of 12.27 +/- 0.32
      months. A majority of the calves were of indigenous breeds (71.37 %) and were
      meant to serve as replacement stock (74.23 %). The tropical livestock unit for
      cattle owned was significantly lower in LB compared to LCB farms (12.71 vs.
      18.85). Significantly higher number of farmers owned non-indigenous calves, had
      clean calf rearing area and reported feed availability in LB farms as compared to
      LCB farms. A majority of farmers (98.50 %) perceived calf morbidity and mortality
      as a major challenge in calf rearing. Meanwhile, labour was readily available to
      assist with calf rearing in 88.24 % of farms in both systems. Capacity building
      on improve husbandry practices could enhance calf survival and productivity in
      surveyed farms. Studies to better identify health and feeding constraints of
      calves will be necessary to define intervention targets. 

PMID- 25778728
TI  - Seasonal variations of the ovarian activity and pregnancy rate in the Egyptian
      buffalo cows (Bubalus bubalis).
AB  - The objective of this study was to investigate the effect of season on the
      follicular and luteal dynamics and pregnancy rate in Egyptian buffaloes. A total
      of 327 genital tracts and 596 animals were used. The genital tracts were examined
      in winter (n = 58), spring (n = 179), summer (n = 49), and autumn (n = 41) for
      follicular population, incidence of presence of developed or mature corpus luteum
      (CL), and diameters of the preovulatory follicle (OF) and the mature CL.
      Buffaloes were mated in winter (n = 297) and summer (n = 299) and examined for
      pregnancy rate. Results showed that the mean number of the large follicles was
      higher in winter (1.21 +/- 0.08 mm) and spring (1.04 +/- 0.05 mm) than in summer
      (0.64 +/- 0.1 mm) and autumn (0.78 +/- 0.1 mm) (P = 0.0001). Likewise, the mean
      diameter of the OF was greater in winter (14.71 +/- 0.7 mm) and spring (14.36 +/-
      0.5 mm) than in summer (12.4 +/- 0.8 mm) and autumn (12 +/- 0.8 mm) (P = 0.02).
      In addition, the mean diameter of the mature CL was higher in winter (15.8 +/-
      0.4 mm) and spring (15.5 +/- 1.1 mm) than in summer (14.2 +/- 1 mm) and autumn
      (13.2 +/- 0.7 mm) (P = 0.003). The incidence of presence of developed or mature
      CL was lower in summer (69.4 %) than in winter (74.1 %), spring (87.2 %), or
      autumn (85.4 %) (P = 0.01). Double CLs (0.9 %) were observed only in spring.
      Ovarian cysts (2.5 %) were detected in winter and spring. The pregnancy rate was
      higher in buffaloes mated in winter (75.4 %) than in those mated in summer (61.9
      %) (P = 0.0004). In conclusion, season affects the ovarian activity and
      reproductive efficiency of buffaloes, where winter and spring are the optimum
      seasons for breeding. 

PMID- 25778729
TI  - Lipopolysaccharide surface structure does not influence IcsA polarity.
AB  - Shigella species are the causative agents of human bacillary dysentery. These
      bacteria spread within the lining of the gut via a process termed actin-based
      motility whereby an actin 'tail' is formed at the bacterial pole. The bacterial
      outer membrane protein IcsA initiates this process, and crucially is precisely
      positioned on the bacterial polar surface. Lipopolysaccharide (LPS) O-antigen
      surface structure has been implicated as an augmenting factor of polarity
      maintenance due to the apparent dysregulation of IcsA polarity in O-antigen
      deficient strains. Due to Shigellae having long and short O-antigen chains on
      their surfaces, it has been proposed that O-antigen chain lengths are
      asymmetrically distributed to optimize IcsA exposure at the pole and mask
      exposure laterally. Additionally, it has been proposed that LPS O-antigen
      restricts IcsA diffusion from the pole by maintaining minimal membrane fluidity.
      This study utilizes minicells and quantitative microscopy providing data refuting
      the models of asymmetric masking and membrane diffusion, and supporting a model
      of symmetric masking of IcsA. We contend that IcsA surface distribution is
      equivalent between wild-type and O-antigen deficient strains, and that
      differences in cellular IcsA levels have confounded previous conclusions. 

PMID- 25778730
TI  - Make social care free at end of life to help more people die at home, say MPs.

PMID- 25778731
TI  - Metazoan Maelstrom is an RNA-binding protein that has evolved from an ancient
      nuclease active in protists.
AB  - Piwi-interacting RNAs (piRNAs) guide Piwi argonautes to their transposon targets
      for silencing. The highly conserved protein Maelstrom is linked to both piRNA
      biogenesis and effector roles in this pathway. One defining feature of Maelstrom
      is the predicted MAEL domain of unknown molecular function. Here, we present the
      first crystal structure of the MAEL domain from Bombyx Maelstrom, which reveals a
      nuclease fold. The overall architecture resembles that found in Mg(2+)- or Mn(2+)
      dependent DEDD nucleases, but a clear distinguishing feature is the presence of a
      structural Zn(2+) ion coordinated by the conserved ECHC residues. Strikingly,
      metazoan Maelstrom orthologs across the animal kingdom lack the catalytic DEDD
      residues, and as we show for Bombyx Maelstrom are inactive as nucleases. However,
      a MAEL domain-containing protein from amoeba having both sequence motifs (DEDD
      and ECHC) is robustly active as an exoribonuclease. Finally, we show that the
      MAEL domain of Bombyx Maelstrom displays a strong affinity for single-stranded
      RNAs. Our studies suggest that the ancient MAEL nuclease domain evolved to
      function as an RNA-binding module in metazoan Maelstrom. 

PMID- 25778732
TI  - Elastin-like recombinamers with acquired functionalities for gene-delivery
      applications.
AB  - In this work, well-defined elastin-like recombinamers (ELRs) were studied as a
      choice to the existing nonviral vectors due to their biocompatibility and ease of
      scale-up. Functional motifs, namely penetratin and LAEL fusogenic peptides were
      incorporated into a basic ELR sequence, and imidazole groups were subsequently
      covalently bound obtaining ELRs with new functionalities. Stable polyplexes
      composed of plasmid DNA and ELRs were formed. A particle size around 200 nm and a
      zeta potential up to nearly +24 mV made them suitable for gene delivery purposes.
      Additionally, viability and transfection assays with C6 rat glioma cell line
      showed an increase in the cellular uptake and transfection levels for the
      construction containing the LAEL motif. This study highlights the importance of
      controlling the polymer functionality using recombinant techniques and
      establishes the utility of ELRs as biocompatible nonviral systems for gene
      therapy applications.

PMID- 25778733
TI  - Global DNA methylation was changed by a maternal high-lipid, high-energy diet
      during gestation and lactation in male adult mice liver.
AB  - An epigenetic mechanism has been suggested to explain the effects of the maternal
      diet on the development of disease in offspring. The present study aimed to
      observe the effects of a maternal high-lipid, high-energy (HLE) diet on the DNA
      methylation pattern of male offspring in mice. Female C57BL/6J mice were fed an
      HLE diet during gestation and lactation. The genomic DNA methylations at promoter
      sites of genes in the liver, mRNA and protein levels of selected genes related to
      lipid and glucose metabolism were measured by microarray, real-time PCR and
      Western blot. The results indicated that the percentage of methylated DNA in
      offspring from dams that were fed an HLE diet was significantly higher than that
      from dams that were fed a chow diet, and most of these genes were hypermethylated
      in promoter regions. The nuclear protein content and mRNA levels of
      hypermethylated genes, such as PPARgamma and liver X receptor alpha (LXRalpha),
      were decreased significantly in offspring in the HLE group. The results suggested
      that the DNA methylation profile in adult offspring livers was changed by the
      maternal HLE diet during gestation and lactation. 

PMID- 25778735
TI  - Assessing numbers and faces: a prerequisite for improving access to lymphatic
      filariasis morbidity care.
AB  - Concerted efforts to eliminate lymphatic filariasis worldwide have registered
      success; multiple rounds of mass drug administration have led to the interruption
      of transmission in many previously endemic areas. However, the management of
      patients with established clinical disease (e.g., lymphoedema, hydrocoele and
      acute dermatolymphangioadenitis) has not been addressed sufficiently. Two recent
      studies from Malawi underscore the need for accurate epidemiological and clinical
      data, and comprehensive morbidity assessments across various domains of daily
      life. Addressing these issues will guide the implementation of programmes to
      improve access to treatment and disability prevention for affected individuals in
      Malawi and beyond. 

PMID- 25778734
TI  - Toxicity and clinical outcomes in patients with HIV on zidovudine and tenofovir
      based regimens: a retrospective cohort study.
AB  - BACKGROUND: Adverse drug reactions are a major concern with zidovudine/stavudine
      treatment regimens. The less toxic tenofovir regimen is an alternative, but is
      seldom considered due to the higher costs. This study compared adverse drug
      reactions and other clinical outcomes resulting from the use of these two
      treatment regimens in India. METHODS: Baseline, clinical characteristics and
      follow-up outcomes were collected by chart reviews of HIV-positive adults and
      compared using univariate/multivariate analysis, with and without propensity
      score adjustments. RESULTS: Data were collected from 129 and 92 patients on
      zidovudine (with lamivudine and nevirapine) and tenofovir (with emtricitabine and
      efavirenz) regimens, respectively. Compared to patients receiving the zidovudine
      regimen, patients receiving the tenofovir regimen had fewer adverse drug
      reactions (47%, 61/129 vs 11%, 10/92; p<0.01), requiring fewer regimen changes
      (36%, 47/129 vs 3%, 3/92; p0.01). With the propensity score, the zidovudine
      regimen had 8 times more adverse drug reactions (p<0.01). Opportunistic
      infections were similar between regimens without propensity score, while the
      zidovudine regimen had 1.2 times (p=0.63) more opportunistic infections with
      propensity score. Patients on the tenofovir regimen gained more weight. Increase
      in CD4 levels and treatment adherence (>95%) was similar across regimens.
      CONCLUSIONS: Patients on a tenofovir regimen have better clinical outcomes and
      improved general health than patients on the zidovudine regimen.

PMID- 25778736
TI  - Predictors of immunological failure and determinants of suboptimal CD4 testing
      among adults with HIV on first-line antiretroviral therapy in Andhra Pradesh,
      India, 2008-2011.
AB  - BACKGROUND: Failure of first-line antiretroviral therapy (ART) results in high
      morbidity and mortality. We identified the predictors of immunological failure
      and suboptimal CD4 testing among adult people living with HIV (PLHIV) initiated
      on first-line ART. METHODS: The cohort of PLHIV aged >= 15 years initiated on
      first-line ART in Hyderabad city, Andhra Pradesh state, in 2008 was followed-up
      until 31 December 2011 or until death and/or lost to follow-up (LFU). We
      estimated cumulative incidence of immunological failure. We explored socio
      demographic, clinical, pharmacological and immunological factors to identify the
      predictors of immunological failure and determinants of suboptimal CD4 testing
      (<2 tests/year). RESULTS: Among the 1431 PLHIV, 275 (19.2%) died and 263 (18.4%)
      were LFU. Of the remaining 893 (62.3%) patients on follow-up, 193 (21.6%)
      experienced immunological failure; these patients were more likely to be males,
      illiterate, with a history of pulmonary TB while on ART and taking stavudine
      based regimen. Incidence of suboptimal testing ranged between 41 and 60% over 4
      years of follow-up. Suboptimal CD4 testing among PLHIV was associated with
      history of TB prior to initiation of ART and stage 3 and 4 of HIV disease at
      enrollment. CONCLUSIONS: There was low immunological failure rate but high
      incidence of suboptimal CD4 testing. The ART centre staff needs to be more
      vigilant about 6-monthly CD4 testing for timely detection of immunological
      failure and appropriate case management.

PMID- 25778737
TI  - Do the angle and length of the eustachian tube influence the development of
      chronic otitis media?
AB  - OBJECTIVES/HYPOTHESIS: To compare the eustachian tube (ET) angle (ETa) and length
      (ETl) of ears with and without chronic otitis media (COM), and to determine the
      relationship between ET anatomy and the development of COM. STUDY DESIGN: A
      retrospective case-control study. METHODS: The study group comprised 125 patients
      (age range, 8-79 years; 64 males and 61 females) with 124 normal ears and 126
      diseased ears, including ears with chronic suppurative otitis media (CSOM) with
      central perforation, intratympanic tympanosclerosis (ITTS), cholesteatoma, and a
      tympanic membrane with retraction pockets (TMRP). ET angle and length were
      measured using computed tomography employing the multiplanar reconstruction
      technique. RESULTS: The ETa was significantly more horizontal in diseased versus
      normal ears of all study groups (P = .030), and there was no group difference in
      ETl (P = .160). ETl was shorter in CSOM versus ITTS ears and normal ears (P =
      .007 and P = .003, respectively) and in cholesteatoma versus TMRP ears (P =
      .014). In the unilateral COM group, there were no significant differences in the
      ETa or ETl of diseased versus contralateral normal ears (P = .155 and P = .710,
      respectively). The ETa was significantly more horizontal in childhood-onset
      diseased versus normal ears (P = .027), and there was no group difference in ETl
      (P = .732). The ETa (P = .002) and ETl (P < .001) were significantly greater in
      males than females. CONCLUSIONS: A more horizontal ETa and shorter ETl could be
      contributory (though not significantly) etiological factors in the development of
      COM. LEVEL OF EVIDENCE: 3b.

PMID- 25778738
TI  - Design and characterization of a composite material based on Sr(II)-loaded clay
      nanotubes included within a biopolymer matrix.
AB  - This paper reports on the preparation, characterization, and cytotoxicity of a
      hybrid nanocomposite material made of Sr(II)-loaded Halloysite nanotubes included
      within a biopolymer (3-polyhydroxybutyrate-co-3-hydroxyvalerate) matrix. The
      Sr(II)-loaded inorganic scaffold is intended to provide mechanical resistance,
      multi-scale porosity, and to favor the in-situ regeneration of bone tissue thanks
      to its biocompatibility and bioactivity. The interaction of the hybrid system
      with the physiological environment is mediated by the biopolymer coating, which
      acts as a binder, as well as a diffusional barrier to the Sr(II) release. The
      degradation of the polymer progressively leads to the exposure of the Sr(II)
      loaded Halloysite scaffold, tuning its interaction with osteogenic cells. The in
      vitro biocompatibility of the composite was demonstrated by cytotoxicity tests on
      L929 fibroblast cells. The results indicate that this composite material could be
      of interest for multiple strategies in the field of bone tissue engineering. 

PMID- 25778739
TI  - Kinetic, isotherm and thermodynamic investigations of phosphate adsorption onto
      core-shell Fe3O4@LDHs composites with easy magnetic separation assistance.
AB  - In this study, three different magnetic core-shell Fe3O4@LDHs composites,
      Fe3O4@Zn-Al-, Fe3O4@Mg-Al-, and Fe3O4@Ni-Al-LDH were prepared via a rapid
      coprecipitation method for phosphate adsorptive removal. The composites were
      characterized by XRD, FTIR, TEM, VSM and BET analyses. Characterization results
      proved the successful synthesis of core-shell Fe3O4@LDHs composites with good
      superparamagnetisms. Batch experiments were conducted to study the adsorption
      efficiency of phosphate. Optimal conditions for the phosphate adsorption were
      obtained: 0.05 g of adsorbent, solution pH of 3, and contact time of 60 min.
      Proposed mechanisms for the removal of phosphate species onto Fe3O4@LDHs
      composites at different initial solution pH were showed. The kinetic data were
      described better by the pseudo-second-order kinetic equation and KASRA model. The
      adsorption isotherm curves showed a three-region behavior in the ARIAN model. It
      had a good fit with Langmuir model and the maximum adsorption capacity followed
      the order of Fe3O4@Zn-Al-LDH>Fe3O4@Mg-Al-LDH>Fe3O4@Ni-Al-LDH. Thermodynamic
      analyses indicated that the phosphate adsorption process was endothermic and
      spontaneous in nature. The three Fe3O4@LDHs composites could be easily separated
      from aqueous solution by the external magnetic field in 10s. These novel magnetic
      core-shell Fe3O4@LDHs adsorbents may offer a simple single step adsorption
      treatment option to remove phosphate from water without the requirement of pre
      /post-treatment for current industrial practice.

PMID- 25778740
TI  - Cardiovascular involvement in pediatric systemic autoimmune diseases: the
      emerging role of noninvasive cardiovascular imaging.
AB  - Cardiac involvement in pediatric systemic autoimmune diseases has a wide spectrum
      of presentation ranging from asymptomatic to severe clinically overt involvement.
      Coronary artery disease, pericardial, myocardial, valvular and rythm disturbances
      are the most common causes of heart lesion in pediatric systemic autoimmune
      diseases and cannot be explained only by the traditional cardiovascular risk
      factors. Therefore, chronic inflammation has been considered as an additive
      causative factor of cardiac disease in these patients. Rheumatic fever, juvenile
      idiopathic arthritis, systemic lupus erythematosus, ankylosing
      spondylitis/spondyloarthritides, juvenile scleroderma, juvenile
      dermatomyositis/polymyositis, Kawasaki disease and other autoimmune vasculitides
      are the commonest pediatric systemic autoimmune diseases with heart involvement.
      Noninvasive cardiovascular imaging is an absolutely necessary adjunct to the
      clinical evaluation of these patients. Echocardiography is the cornerstone of
      this assessment, due to excellent acoustic window in children, lack of radiation,
      low cost and high availability. However, it can not detect disease acuity and
      pathophysiologic background of cardiac lesions. Recently, the development of
      cardiovascular magnetic resonance imaging holds the promise for early detection
      of subclinical heart disease and detailed serial evaluation of myocardium
      (function, inflammation, stress perfusion-fibrosis) and coronary arteries
      (assessment of ectasia and aneurysms). </p>. 

PMID- 25778741
TI  - Smoking and dental implants: A systematic review and meta-analysis.
AB  - OBJECTIVE: Recent studies implicate smoking as a significant factor in the
      failure of dental implants. This review aims to test the null hypothesis of no
      difference in the implant failure rates, risk of postoperative infection, and
      marginal bone loss for smokers versus non-smokers, against the alternative
      hypothesis of a difference. DATA: Main search terms used in combination: dental
      implant, oral implant, smoking, tobacco, nicotine, smoker, and non-smoker.
      SOURCES: An electronic search was undertaken in September/2014 in PubMed/Medline,
      Web of Science, Cochrane Oral Health Group Trials Register plus hand-searching.
      STUDY SELECTION: Eligibility criteria included clinical human studies, either
      randomized or not. The search strategy resulted in 1432 publications, of which
      107 were eligible, with 19,836 implants placed in smokers, with 1259 failures
      (6.35%), and 60,464 implants placed in non-smokers, with 1923 failures (3.18%).
      CONCLUSIONS: The insertion of implants in smokers significantly affected the
      failure rates, the risk of postoperative infections as well as the marginal bone
      loss. The results should be interpreted with caution due to the presence of
      uncontrolled confounding factors in the included studies. CLINICAL SIGNIFICANCE:
      Smoking is a factor that has the potential to negatively affect healing and the
      outcome of implant treatment. It is important to perform an updated periodic
      review to synthesize the clinical research evidence relevant to the matter.

PMID- 25778742
TI  - HBx co-localizes with COXIII in HL-7702 cells to upregulate mitochondrial
      function and ROS generation.
AB  - Hepatocellular carcinoma (HCC) is one of the most common malignant diseases, and
      HBx leads to the development of HBV-associated HCC. Mitochondria are key
      organelles that regulate apoptosis, cellular energetics and signal transduction
      pathways, and are the source of HBx-induced reactive oxygen species (ROS). Recent
      findings have shown that HBx interacts with the inner mitochondrial membrane
      protein, COXIII, via the yeast two-hybrid system, mating experiment and
      coimmunoprecipitation. The aim of the present study was to examine the co
      localizaiton of HBx and COXIII in HL-7702 cells and to investigate ensuing
      alterations of mitochondrial function. An HL-7702 cell line stably expressing the
      HBx gene by lentivirus vectors was constructed. Confocal microscopy was utilized
      to assess the interaction between HBx protein and COXIII. Expression of COXIII,
      activities of cytochrome c oxidase (COX) and the mitochondrial membrane
      potential, which were functionally relevant to the HBx protein-COXIII
      interaction, were investigated in cell cultures. Moreover, the intracellular ROS
      levels were detected by flow cytometry. The results demonstrated that HBx co
      localized with the inner mitochondrial protein, COXIII, in HL-7702 cells, causing
      the upregulation of COXIII protein expression as well as COX activity. However,
      HBx did not alter the mitochondrial membrane potential and mitochondria exhibited
      only slight swelling in HL-7702-HBx cells. Moreover, HBx elevated the generation
      of mitochondrial ROS in HL-7702-HBx cells. The main finding of the present study
      was that the co-localization of HBx and COXIII leads to upregulation of the
      mitochondrial function and ROS generation, which are associated with the
      oncogenesis of HBV-associated HCC.

PMID- 25778743
TI  - The prevalence and diagnostic utility of systemic inflammatory response syndrome
      vital signs in a pediatric emergency department.
AB  - OBJECTIVES: This study sought to determine the prevalence, test characteristics,
      and severity of illness of pediatric patients with systemic inflammatory response
      syndrome (SIRS) vital signs among pediatric emergency department (ED) visits.
      METHODS: This was a retrospective descriptive cohort study of all visits to the
      ED of a tertiary academic free-standing pediatric hospital over 1 year. Visits
      were included if the patient was <18 years of age and did not leave before full
      evaluation or against medical advice. Exclusion criteria were trauma diagnoses or
      missing documentation of vital signs. Data were electronically extracted from the
      medical record. The primary predictor was presence of vital signs meeting
      pediatric SIRS definitions. Specific vital sign pairs comprising SIRS were
      evaluated as predictors (temperature-heart rate, temperature-respiratory rate,
      and temperature-corrected heart rate, in which a formula was used to correct
      heart rate for degree of temperature elevation). The primary outcome measure was
      requirement for critical care (receipt of a vasoactive agent or intubation)
      within 24 hours of ED arrival. RESULTS: There were 56,210 visits during the study
      period; 40,356 met inclusion criteria. Of these, 6,596 (16.3%) visits had fever
      >38.5 degrees C, and 6,122 (15.2% of included visits) met SIRS vital sign
      criteria. Among included visits, those with SIRS vital signs accounted for 92.8%
      of all visits with fever >38.5 degrees C. Among patients with SIRS vital signs,
      4993 (81.6%) were discharged from the ED without intravenous (IV) therapy and
      without 72-hour readmission. Critical care within the first 24 hours was present
      in 99 (0.25%) patients: 23 patients with and 76 without SIRS vital signs.
      Intensive care unit (ICU) admission was present in 126 (2.06%) with SIRS vital
      signs and 487 (1.42%) without SIRS vital signs. SIRS vital signs were associated
      with increased risk of critical care within 24 hours (relative risk [RR] = 1.69,
      95% confidence interval [CI] = 1.06 to 2.70), ICU admission (RR = 1.45, 95% CI =
      1.19 to 1.76), ED laboratory tests (RR = 1.41, 95% CI = 1.37 to 1.45), ED IV
      medication/fluid administration (RR = 2.54, 95% CI = 2.29 to 2.82), hospital
      admission (RR = 1.52, 95% CI = 1.42 to 1.63), and 72-hour readmission (RR = 1.31,
      95% CI = 1.01 to 1.69). SIRS vital signs were not associated with 30-day in
      hospital mortality (RR = 0.37, 95% CI = 0.05 to 2.82). SIRS vital signs had a low
      sensitivity for critical care requirement (23.2%, 95% CI = 15.3% to 32.8%). The
      pair of SIRS vital signs with the strongest association with critical care
      requirement was temperature and corrected heart rate (positive likelihood ratio =
      2.74, 95% CI = 1.87 to 4.01). CONCLUSIONS: Systemic inflammatory response
      syndrome vital signs are common among medical pediatric patients presenting to an
      ED, and critical illness is rare. The majority of patients with SIRS vital signs
      were discharged without IV therapy and without readmission. Patients with SIRS
      vital signs had a statistically significant increased risk of critical care
      requirement, ED IV treatment, ED laboratory tests, admission, and readmission.
      However, SIRS vital sign criteria did not identify the majority of patients with
      mortality or need for critical care. SIRS vital signs had low sensitivity for
      critical illness, making it poorly suited for use in isolation in this setting as
      a test to detect children requiring sepsis resuscitation.

PMID- 25778745
TI  - Reproductive performance response to the male effect in goats is improved when
      doe live weight/body condition score is increasing.
AB  - This study examines the nutritional and metabolic cue-induced modulation of the
      reproductive performance response of female goats to the male effect. During
      natural anoestrus, 48 Blanca Andaluza does were isolated from bucks for 45 days
      and distributed into two groups: (1) low body weight (BW)/low body condition
      score (BCS) animals (LL-gain group, N=18), which were fed 1.9 times their
      maintenance requirements; and (2) high BW/high BCS animals (HH-loss group, N=30),
      which were fed 0.4 times their maintenance requirements. Following isolation,
      oestrous activity was recorded daily by visual observation of the marks left by
      harness-equipped males. Weekly blood samples were taken for the determination of
      progesterone, glucose, insulin, non-esterified fatty acids (NEFAs) and leptin
      concentrations. Fecundity, fertility, prolificacy and productivity were also
      determined. Significantly greater ovarian and oestrous responses, and
      productivity, were observed in the LL-gain group compared to the HH-loss group
      (P<0.05). After the introduction to the males, no differences in NEFA
      concentration were seen between the groups; before introduction the values were
      higher in the HH-loss group. At the moment of detection of oestrus following male
      introduction, the insulin concentration of the LL-gain animals was higher
      (P<0.05). The present results show that the reproductive performances of does
      subjected to the male effect in spring are poorer in those with a decreasing BW
      and BCS and better in those with increasing scores. This might be explained by
      the differences between groups in terms of their plasma insulin concentrations.
      The NEFA concentration was clearly modified by introduction to the males. 

PMID- 25778744
TI  - Hip Osteoarthritis and the Risk of All-Cause and Disease-Specific Mortality in
      Older Women: A Population-Based Cohort Study.
AB  - OBJECTIVE: To determine the risk of all-cause and disease-specific mortality
      among older women with hip osteoarthritis (OA) and to identify mediators in the
      causal pathway. METHODS: Data were from the Study of Osteoporotic Fractures, a US
      population-based cohort study of 9,704 white women age >=65 years. The analytic
      sample included women with hip radiographs at baseline (n = 7,889) and year 8 (n
      = 5,749). Mortality was confirmed through October 2013 by death certificates and
      hospital discharge summaries. Radiographic hip OA (RHOA) was defined as a Croft
      grade of >=2 in at least 1 hip (definite joint space narrowing or osteophytes
      plus 1 other radiographic feature). RESULTS: The mean +/- SD followup time was
      16.1 +/- 6.2 years. The baseline and year 8 prevalence of RHOA were 8.0% and
      11.0%, respectively. The cumulative incidence (proportion of deaths during the
      study period) was 67.7% for all-cause mortality, 26.3% for cardiovascular disease
      (CVD) mortality, 11.7% for cancer mortality, 1.9% for gastrointestinal disease
      mortality, and 27.8% for all other mortality causes. RHOA was associated with an
      increased risk of all-cause mortality (hazard ratio 1.14 [95% confidence interval
      1.05-1.24]) and CVD mortality (hazard ratio 1.24 [95% confidence interval 1.09
      1.41]) adjusted for age, body mass index, education, smoking, health status,
      diabetes, and stroke. These associations were partially explained by the
      mediating variable of physical function. CONCLUSION: RHOA was associated with an
      increased risk of all-cause and CVD mortality among older white women followed up
      for 16 years. Dissemination of evidence-based physical activity and self
      management interventions for hip OA in community and clinical settings can
      improve physical function and might also contribute to lower mortality.

PMID- 25778746
TI  - Evaluation of N-acetyl-S-(p-chlorophenylcarbamoyl)cysteine as an irreversible
      inhibitor of mammalian thioredoxin reductase1.
AB  - CONTEXT: Thioredoxin reductase (TrxR) is up-regulated in a number of human
      malignant cells and becomes a promising target for anticancer drug development.
      OBJECTIVE: To evaluate N-acetyl-S-(p-chlorophenylcarbamoyl)cysteine (NACC), a
      potent anticancer agent against melanoma, as an inhibitor of mammalian TrxR1.
      MATERIAL AND METHODS: The mechanism of inhibition against TrxR1 was investigated
      using substrate protection, dialysis and liquid chromatography-tandem mass
      spectrometry. RESULTS: NACC inhibits TrxR1 in a time and concentration dependent
      manner. The K(I) and k(inact) of NACC against TrxR1 were determined to be 80 MUM
      and 0.178 min(-1), respectively. The inhibition occurred only in the presence of
      NADPH and persisted after extensive dialysis. The tandem mass spectrometric
      analysis demonstrated that the selenocysteine rather than cysteine residue at the
      active site was p-chlorophenyl carbamoylated by NACC. Inhibition of intracellular
      TrxR by NACC in cultured melanoma cells was observed. DISCUSSION AND CONCLUSION:
      NACC which irreversibly inhibits TrxR1 by forming a covalent bond with
      selenocysteine can be an effective tool in the study of TrxR1.

PMID- 25778747
TI  - The cost-effectiveness, health benefits, and financial costs of new antiviral
      treatments for hepatitis C virus.
AB  - BACKGROUND: New hepatitis C virus (HCV) treatments deliver higher cure rates with
      fewer contraindications, increasing demand for treatment and healthcare costs.
      The cost-effectiveness of new treatments is unknown. METHODS: We conducted a
      microsimulation of guideline testing followed by alternative treatment regimens
      for HCV among the US population aged 20 and older to estimate cases identified,
      treated, sustained viral response, deaths, medical costs, quality-adjusted life
      years (QALYs), and the incremental cost-effectiveness ratio (ICER) of different
      treatment options expressed as discounted lifetime costs and benefits from the
      healthcare perspective. RESULTS: Compared to treatment with pegylated interferon
      and ribavirin (PR), and a protease inhibitor for HCV genotype (G) 1 and PR alone
      for G2/3, treatment with PR and Sofosbuvir (PRS) for G1/4 and treatment with
      Sofosbuvir and ribavirin (SR) for G2/3 increased QALYs by 555 226, reduced deaths
      by 80 682, and increased costs by $26.2 billion at an ICER of $47 304 per QALY
      gained. As compared to PRS/SR, treating with an all oral regimen of Sofosbuvir
      and Simeprevir (SS) for G1/4 and SR for G2/3, increased QALYs by 1 110 451 and
      reduced deaths by an additional 164 540 at an incremental cost of $80.1 billion
      and an ICER of $72 169. In sensitivity analysis, where treatment with SS
      effectiveness was set to the list price of Viekira Pak and then Harvoni,
      treatment cost $24 921 and $25 405 per QALY gained as compared to PRS/SR.
      CONCLUSIONS: New treatments are cost-effectiveness per person treated, but pent
      up demand for treatment may create challenges for financing.

PMID- 25778748
TI  - Editorial commentary: getting smart in how we pay for HCV drugs: KAOS vs CONTROL.

PMID- 25778749
TI  - Proof-of-Principle for Immune Control of Global HIV-1 Reactivation In Vivo.
AB  - BACKGROUND: Emerging data relating to human immunodeficiency virus type 1 (HIV-1)
      cure suggest that vaccination to stimulate the host immune response, particularly
      cytotoxic cells, may be critical to clearing of reactivated HIV-1-infected cells.
      However, evidence for this approach in humans is lacking, and parameters required
      for a vaccine are unknown because opportunities to study HIV-1 reactivation are
      rare. METHODS: We present observations from a HIV-1 elite controller, not treated
      with combination antiretroviral therapy, who experienced viral reactivation
      following treatment for myeloma with melphalan and autologous stem cell
      transplantation. Mathematical modeling was performed using a standard viral
      dynamic model. Enzyme-linked immunospot, intracellular cytokine staining, and
      tetramer staining were performed on peripheral blood mononuclear cells; in vitro
      CD8 T-cell-mediated control of virion production by autologous CD4 T cells was
      quantified; and neutralizing antibody titers were measured. RESULTS: Viral
      rebound was measured at 28,000 copies/mL on day 13 post-transplant before rapid
      decay to <50 copies/mL in 2 distinct phases with t1/2 of 0.71 days and 4.1 days.
      These kinetics were consistent with an expansion of cytotoxic effector cells and
      killing of productively infected CD4 T cells. Following transplantation, innate
      immune cells, including natural killer cells, recovered with virus rebound.
      However, most striking was the expansion of highly functional HIV-1-specific
      cytotoxic CD8 T cells, at numbers consistent with those applied in modeling, as
      virus control was regained. CONCLUSIONS: These observations provide evidence that
      the human immune response is capable of controlling coordinated global HIV-1
      reactivation, remarkably with potency equivalent to combination antiretroviral
      therapy. These data will inform design of vaccines for use in HIV-1 curative
      interventions.

PMID- 25778752
TI  - Invasive Pulmonary Aspergillosis-mimicking Tuberculosis.
AB  - BACKGROUND: Pulmonary tuberculosis is occasionally confused with invasive
      pulmonary aspergillosis (IPA) in transplant recipients, since clinical suspicion
      and early diagnosis of pulmonary tuberculosis and IPA rely heavily on imaging
      modes such as computed tomography (CT). We therefore investigated IPA-mimicking
      tuberculosis in transplant recipients. METHODS: All adult transplant recipients
      who developed tuberculosis or IPA at a tertiary hospital in an intermediate
      tuberculosis-burden country during a 6-year period were enrolled. First, we
      tested whether experienced radiologists could differentiate pulmonary
      tuberculosis from IPA. Second, we determined which radiologic findings could help
      us differentiate them. RESULTS: During the study period, 28 transplant recipients
      developed pulmonary tuberculosis after transplantation, and 80 patients developed
      IPA after transplantation. Two experienced radiologists scored blindly 28
      tuberculosis and 50 randomly selected IPA cases. The sensitivities of
      radiologists A and B for IPA were 78% and 68%, respectively (poor agreement,
      kappa value = 0.25). The sensitivities of radiologists A and B for tuberculosis
      were 64% and 61%, respectively (excellent agreement, kappa value = 0.77). We then
      compared the CT findings of the 28 patients with tuberculosis and 80 patients
      with IPA. Infarct-shaped consolidations and smooth bronchial wall thickening were
      more frequent in IPA, and mass-shaped consolidations and centrilobular nodules
      (<10 mm, clustered) were more frequent in tuberculosis. CONCLUSIONS: Certain CT
      findings appear to be helpful in differentiating between IPA and tuberculosis.
      Nevertheless, the CT findings of about one-third of pulmonary tuberculosis cases
      in transplant recipients are very close to those of IPA.

PMID- 25778751
TI  - Reduced Mortality of Cytomegalovirus Pneumonia After Hematopoietic Cell
      Transplantation Due to Antiviral Therapy and Changes in Transplantation
      Practices.
AB  - BACKGROUND: Despite major advances in the prevention of cytomegalovirus (CMV)
      disease, the treatment of CMV pneumonia in recipients of hematopoietic cell
      transplant remains a significant challenge. METHODS: We examined recipient,
      donor, transplant, viral, and treatment factors associated with overall and
      attributable mortality using Cox regression models. RESULTS: Four hundred twenty
      one cases were identified between 1986 and 2011. Overall survival at 6 months was
      30% (95% confidence interval [CI], 25%-34%). Outcome improved after the year 2000
      (all-cause mortality: adjusted hazard ratio [aHR], 0.7 [95% CI, .5-1.0]; P = .06;
      attributable mortality: aHR, 0.6 [95% CI, .4-.9]; P = .01). Factors independently
      associated with an increased risk of all-cause and attributable mortality
      included female sex, elevated bilirubin, lymphopenia, and mechanical ventilation;
      grade 3/4 acute graft-vs-host disease was associated with all-cause mortality
      only. An analysis of patients who received transplants in the current preemptive
      therapy era (n = 233) showed only lymphopenia and mechanical ventilation as
      significant risk factors for overall and attributable mortality. Antiviral
      treatment with ganciclovir or foscarnet was associated with improved outcome
      compared with no antiviral treatment. However, the addition of intravenous pooled
      or CMV-specific immunoglobulin to antiviral treatment did not seem to improve
      overall or attributable mortality. CONCLUSIONS: Outcome of CMV pneumonia showed a
      modest improvement over the past 25 years. However, advances seem to be due to
      antiviral treatment and changes in transplant practices rather than
      immunoglobulin-based treatments. Novel treatment strategies for CMV pneumonia are
      needed.

PMID- 25778750
TI  - Cannabis Use and Reduced Risk of Insulin Resistance in HIV-HCV Infected Patients:
      A Longitudinal Analysis (ANRS CO13 HEPAVIH).
AB  - BACKGROUND: Diabetes and insulin resistance (IR) is common in human
      immunodeficiency virus-hepatitis C virus (HIV-HCV)-coinfected patients, a
      population also concerned with elevated cannabis use. Cannabis has been
      associated with reduced IR risk in some population-based surveys. We determined
      whether cannabis use was consistently associated with reduced IR risk in HEPAVIH,
      a French nationwide cohort of HIV-HCV-coinfected patients. METHODS: HEPAVIH
      medical and sociobehavioral data were collected (using annual self-administered
      questionnaires). We used 60 months of follow-up data for patients with at least 1
      medical visit where IR (using homeostatic model assessment of insulin resistance
      [HOMA-IR]) and cannabis use were assessed. A mixed logistic regression model was
      used to evaluate the association between IR risk (HOMA-IR > 2.77) and cannabis
      use (occasional, regular, daily). RESULTS: Among the 703 patients included in the
      study (1287 visits), 323 (46%) had HOMA-IR > 2.77 for at least 1 follow-up visit
      and 319 (45%) reported cannabis use in the 6 months before the first available
      visit. Cannabis users (irrespective of frequency) were less likely to have HOMA
      IR > 2.77 (odds ratio [95% confidence interval], 0.4 [.2-.5]) after adjustment
      for known correlates/confounders. Two sensitivity analyses with HOMA-IR values as
      a continuous variable and a cutoff value of 3.8 confirmed the association between
      reduced IR risk and cannabis use. CONCLUSIONS: Cannabis use is associated with a
      lower IR risk in HIV-HCV-coinfected patients. The benefits of cannabis-based
      pharmacotherapies for patients concerned with increased risk of IR and diabetes
      need to be evaluated in clinical research and practice.

PMID- 25778755
TI  - Lennox-Gastaut syndrome may be a curable, reversible epileptic encephalopathy.

PMID- 25778753
TI  - Pharmacodynamic Modeling of Bacillary Elimination Rates and Detection of
      Bacterial Lipid Bodies in Sputum to Predict and Understand Outcomes in Treatment
      of Pulmonary Tuberculosis.
AB  - BACKGROUND: Antibiotic-tolerant bacterial persistence prevents treatment
      shortening in drug-susceptible tuberculosis, and accumulation of intracellular
      lipid bodies has been proposed to identify a persister phenotype of Mycobacterium
      tuberculosis cells. In Malawi, we modeled bacillary elimination rates (BERs) from
      sputum cultures and calculated the percentage of lipid body-positive acid-fast
      bacilli (%LB + AFB) on sputum smears. We assessed whether these putative
      measurements of persistence predict unfavorable outcomes (treatment
      failure/relapse). METHODS: Adults with pulmonary tuberculosis received standard 6
      month therapy. Sputum samples were collected during the first 8 weeks for serial
      sputum colony counting (SSCC) on agar and time-to positivity (TTP) measurement in
      mycobacterial growth indicator tubes. BERs were extracted from nonlinear and
      linear mixed-effects models, respectively, fitted to these datasets. The %LB +
      AFB counts were assessed by fluorescence microscopy. Patients were followed until
      1 year posttreatment. Individual BERs and %LB + AFB counts were related to final
      outcomes. RESULTS: One hundred and thirty-three patients (56% HIV coinfected)
      participated, and 15 unfavorable outcomes were reported. These were inversely
      associated with faster sterilization phase bacillary elimination from the SSCC
      model (odds ratio [OR], 0.39; 95% confidence interval [CI], .22-.70) and a faster
      BER from the TTP model (OR, 0.71; 95% CI, .55-.94). Higher %LB + AFB counts on
      day 21-28 were recorded in patients who suffered unfavorable final outcomes
      compared with those who achieved stable cure (P = .008). CONCLUSIONS: Modeling
      BERs predicts final outcome, and high %LB + AFB counts 3-4 weeks into therapy may
      identify a persister bacterial phenotype. These methods deserve further
      evaluation as surrogate endpoints for clinical trials.

PMID- 25778756
TI  - In response: Lennox-Gastaut syndrome may be a curable, reversible epileptic
      encephalopathy.

PMID- 25778757
TI  - Improving the outcome of umbilical cord blood transplantation through ex vivo
      expansion or graft manipulation.
AB  - The outcome of umbilical cord blood transplantation for adult patients with
      hematologic malignancies now rivals that of matched unrelated donor
      transplantation. However, relatively low lymphocyte and hematopoietic stem and
      progenitor cell dose is a source of significant morbidity and mortality. Multiple
      strategies are now being studied to overcome these limitations. One strategy
      involves ex vivo expansion of the umbilical cord blood unit before
      transplantation. Ex vivo expansion has the potential to increase the number of
      lymphocytes, committed progenitors and long-term repopulating hematopoietic stem
      cells. Increasing the numbers of lymphocytes and committed progenitor cells will
      address the issue of delayed hematopoietic recovery after umbilical cord blood
      transplantation. Increasing the hematopoietic stem cell content will improve the
      availability of adequately sized and matched cord blood units for
      transplantation. It may also eliminate the need for dual umbilical cord blood
      transplantation for those without an adequately sized single umbilical cord blood
      graft. The second strategy involves exposure of the umbilical cord blood graft to
      compounds aimed at improving homing and engraftment following transplantation.
      Such a strategy may also address the problem of slow hematopoietic recovery as
      well as the increased risk of graft failure. Many of these strategies are now
      being tested in late-phase multi-center clinical trials. If proven cost-effective
      and efficacious, they may alter the landscape of donor options for allogeneic
      stem cell transplantation.

PMID- 25778758
TI  - Insects as models to study the epigenetic basis of disease.
AB  - Epigenetic inheritance refers to changes in gene expression that are heritable
      across generations but are not caused by changes in the DNA sequence. Many
      environmental factors are now known to cause epigenetic changes, including the
      presence of pathogens, parasites, harmful chemicals and other stress factors.
      There is increasing evidence that transcriptional reprogramming caused by
      epigenetic modifications can be passed from parents to offspring. Indeed,
      diseases such as cancer can occur in the offspring due to epigenetically
      inherited gene expression profiles induced by stress experienced by the parent.
      Empirical studies to investigate the role of epigenetics in trans-generational
      gene regulation and disease require appropriate model organisms. In this review,
      we argue that selected insects can be used as models for human diseases with an
      epigenetic component because the underlying molecular mechanisms (DNA
      methylation, histone acetylation and the expression of microRNAs) are
      evolutionarily conserved. Insects offer a number of advantages over mammalian
      models including ethical acceptability, short generation times and the potential
      to investigate complex interacting parameters such as fecundity, longevity,
      gender ratio, and resistance to pathogens, parasites and environmental stress. 

PMID- 25778759
TI  - Comparative analysis of time series of marine litter surveyed on beaches and the
      seafloor in the southeastern North Sea.
AB  - The comparative analysis of marine litter in different marine compartments has
      rarely been attempted. In this study, long-term time series of marine litter
      abundance on the seafloor and on the coast, both from the southeastern North Sea,
      were analyzed for temporal trends and correlations. On four beach sections of 100
      m length, mean abundances of total beach litter collected four times a year from
      2002 to 2008 varied between 105 and 435 items. Mean densities of total inorganic
      litter on the seafloor amounted to 10.6 +/- 9.7 kg km(-2) in the offshore region
      (2001-2010) and 13.7 +/- 12.6 kg km(-2) in the Wadden Sea (1998-2007),
      respectively. In the offshore region, there was no significant long-term trend,
      while in the Wadden Sea, densities of marine litter declined significantly.
      Correlations between time series were weak, indicating different sources and
      transport processes responsible for compositions of beach litter and litter on
      the seafloor. Decreases in inputs from fisheries and substantial export due to
      resuspension are discussed as reasons for the decrease in litter on the seafloor
      in the Wadden Sea.

PMID- 25778760
TI  - [An unusual vulvar tumour].

PMID- 25778762
TI  - [A cause of palatal necrosis not to ignore].
AB  - We report a case of pseudotumoral nasal septum and hard palate perforation in a
      42-years-old man. The diagnosis retained after differential diagnosis exclusion
      was necrotic midfacial lesion due to chronic inhalation of cocaine. This
      condition can mimic vasculitis, primary tumors and granulomatous infections.
      Differential diagnosis and pathophysiology of this condition will be discussed in
      this anatomo-clinical case. 

PMID- 25778761
TI  - [Cutaneous lymphoproliferations: proposal for the use of diagnostic algorithms
      based on 2760 cases of cutaneous lymphoproliferations taken from the INCa
      networks (LYMPHOPATH and GFELC) over a two-year period].
AB  - INTRODUCTION: Taking as a base our retrospective study of 2760 cases of cutaneous
      lymphoproliferations from the LYMPHOPATH and GFELC networks, we analyzed the
      doubtful and discordant cases between non-expert and expert pathologists, and the
      interest of clinicopathological confrontation. MATERIAL AND METHODS: We defined
      the main diagnostic difficulties presented by cutaneous lymphoproliferations. We
      then designed and tested the algorithms on 20 random cases with 20 pathologists,
      in order to be used by any pathologist (not necessarily specialised in
      dermatopathology). RESULTS: The problematic differential diagnoses most
      frequently encountered are the following: MF or reactive dermatose; lymphoma
      without any other precision or reactive infiltrate; small B cell
      lymphoproliferation: lymphoma or reactive infiltrate; phenotyping of large B cell
      lymphoproliferation. We also analyzed less common problematic differential
      diagnoses, on the grounds that they are over- or under- diagnosed. Our test had a
      72% success rate among the 20 randomly tested cases. The use of several
      algorithms for the same case is possible. DISCUSSION: Our study shows that an
      expert second-opinion is of interest in the area of cutaneous
      lymphoproliferations. A second opinion is useful for distinguishing a small B
      cell lymphoma from a HLR, and for defining a final diagnosis when the first
      pathologist doubts between lymphoma and reactive infiltrate. However, we
      demonstrate that for the problem MF or reactive dermatose, an initial
      clinicopathological confrontation produces more results than a second-opinion
      pathology review. CONCLUSION: This is the first study of cutaneous
      lymphoproliferations that, without excluding reactionary infiltrates,
      concentrates on doubtful and discordant diagnoses between non expert and expert
      pathologists, and which has produced tested diagnostic algorithms.

PMID- 25778763
TI  - [A posterior mediastinal mass...].

PMID- 25778764
TI  - Coherence time limit of the biphotons generated in a dense cold atom cloud.
AB  - Biphotons with narrow bandwidth and long coherence time can enhance light-atom
      interaction, which leads to strong coupling between photonic and atomic qubits.
      Such strong coupling is desirable in quantum information processing, quantum
      storage and communication. In particular, paired photons with a long coherence
      time over submicroseconds facilitate the direct manipulation of biphoton
      wavefunction. In this paper, we report the narrow-band biphotons with a coherence
      time of 2.34 MUs generated from spontaneous four-wave mixing (SFWM) in a dense
      cold atom cloud, in which the anti-Stokes photons go through a narrow
      electromagnetically-induced transparency (EIT) window. In our knowledge, this is
      the best record of coherence time for paired photons achieved so far. A number of
      factors limiting the coherence time are analyzed in detail. We find the EIT
      coherence plays an essential role in determining the coherence time for paired
      photons. The EIT dephasing rate is the ultimate limit to the coherence time, and
      an ultra-long coherence time above ten microseconds is possible by further
      improvement of the dephasing rate below 100 kHz.

PMID- 25778765
TI  - 'We keep her status to ourselves': experiences of stigma and discrimination among
      HIV-discordant couples in South Africa, Tanzania and Ukraine.
AB  - In HIV-discordant relationships, the HIV-negative partner also carries the burden
      of a stigmatised disease. For this reason, couples often hide their HIV
      discordant status from family, friends and community members. This perpetuates
      the silence around HIV-discordant relationships and impacts on targeted HIV
      prevention, treatment and counselling efforts. This article reports on
      experiences of stigma and discrimination among HIV-discordant couples in South
      Africa, Tanzania and Ukraine. During 2008, HIV-discordant couples who had been in
      a relationship for at least one year were recruited purposively through health
      care providers and civil society organisations in the three countries.
      Participants completed a brief self-administered questionnaire, while semi
      structured interviews were conducted with each partner separately and with both
      partners together. Interviews were analysed using thematic content analysis.
      Fifty-one couples were recruited: 26 from South Africa, 10 from Tanzania, and 15
      from Ukraine. Although most participants had disclosed their HIV status to
      someone other than their partner, few were living openly with HIV discordance.
      Experiences of stigma were common and included being subjected to gossip, rumours
      and name-calling, and HIV-negative partners being labelled as HIV-positive.
      Perpetrators of discrimination included family members and health workers. Stigma
      and discrimination present unique and complex challenges to couples in HIV sero
      discordant relationships in these three diverse countries. Addressing
      stigmatisation of HIV-discordant couples requires a holistic human rights
      approach and specific programme efforts to address discrimination in the health
      system. 

PMID- 25778766
TI  - Synthesis and biological evaluation of benzimidazole acridine derivatives as
      potential DNA-binding and apoptosis-inducing agents.
AB  - The discovery of new effective DNA-targeted antitumor agent is needed because of
      their clinical significance. As acridines can intercalate into DNA and
      benzimidazoles have the ability to bind in the DNA minor groove, a series of
      novel benzimidazole acridine derivatives were designed and synthesized to be new
      DNA-targeted compounds. MTT assay indicated that most of the synthesized
      compounds displayed good antiproliferative activity, among which compound 8l
      demonstrated the highest activity against both K562 and HepG-2 cells. Further
      experiments showed that 8l displayed good DNA-binding capability and inhibited
      topoisomerase I activity. Moreover, compound 8l could induce apoptosis in K562
      cell lines through mitochondrial pathway. These data suggested that compound 8l
      might be potential as new DNA-binding and apoptosis-inducing antitumor agents. 

PMID- 25778767
TI  - Synthesis and biological activity of novel mono-indole and mono-benzofuran
      inhibitors of bacterial transcription initiation complex formation.
AB  - Our ongoing research focused on targeting transcription initiation in bacteria
      has resulted in synthesis of several classes of mono-indole and mono-benzofuran
      inhibitors that targeted the essential protein-protein interaction between RNA
      polymerase core and sigma(70)/sigma(A) factors in bacteria. In this study, the
      reaction of indole-2-, indole-3-, indole-7- and benzofuran-2-glyoxyloyl chlorides
      with amines and hydrazines afforded a variety of glyoxyloylamides and
      glyoxyloylhydrazides. Similarly, condensation of 2- and 7-trichloroacetylindoles
      with amines and hydrazines delivered amides and hydrazides. The novel molecules
      were found to inhibit the RNA polymerase-sigma(70)/sigma(A) interaction as
      measured by ELISA, and also inhibited the growth of both Gram-positive and Gram
      negative bacteria in culture. Structure-activity relationship (SAR) studies of
      the mono-indole and mono-benzofuran inhibitors suggested that the hydrophilic
      hydrophobic balance is an important determinant of biological activity.

PMID- 25778768
TI  - Base-modified thymidines capable of terminating DNA synthesis are novel bioactive
      compounds with activity in cancer cells.
AB  - Current FDA-approved chemotherapeutic antimetabolites elicit severe side effects
      that warrant their improvement; therefore, we designed compounds with mechanisms
      of action focusing on inhibiting DNA replication rather than targeting multiple
      pathways. We previously discovered that 5-(alpha-substituted-2
      nitrobenzyloxy)methyluridine-5'-triphosphates were exquisite DNA synthesis
      terminators; therefore, we synthesized a library of 35 thymidine analogs and
      evaluated their activity using an MTT cell viability assay of MCF7 breast cancer
      cells chosen for their vulnerability to these nucleoside derivatives. Compound
      3a, having an alpha-tert-butyl-2-nitro-4-(phenyl)alkynylbenzyloxy group, showed
      an IC50 of 9+/-1MUM. The compound is more selective for cancer cells than for
      fibroblast cells compared with 5-fluorouracil. Treatment of MCF7 cells with 3a
      elicits the DNA damage response as indicated by phosphorylation of gamma-H2A. A
      primer extension assay of the 5'-triphosphate of 3a revealed that 3aTP is more
      likely to inhibit DNA polymerase than to lead to termination events upon
      incorporation into the DNA replication fork. 

PMID- 25778769
TI  - Structure-activity studies in the development of a hydrazone based inhibitor of
      adipose-triglyceride lipase (ATGL).
AB  - Adipose triglyceride lipase (ATGL) catalyzes the degradation of cellular
      triacylglycerol stores and strongly determines the concentration of circulating
      fatty acids (FAs). High serum FA levels are causally linked to the development of
      insulin resistance and impaired glucose tolerance, which eventually progresses to
      overt type 2 diabetes. ATGL-specific inhibitors could be used to lower
      circulating FAs, which can counteract the development of insulin resistance. In
      this article, we report about structure-activity relationship (SAR) studies of
      small molecule inhibitors of ATGL based on a hydrazone chemotype. The SAR
      indicated that the binding pocket of ATGL requests rather linear compounds
      without bulky substituents. The best inhibitor showed an IC50=10MUM in an assay
      with COS7-cell lysate overexpressing murine ATGL.

PMID- 25778770
TI  - Re: 'Galectin-3, carotid plaque vulnerability, and potential effects of statin
      therapy'.

PMID- 25778771
TI  - Managing chronic venous disease: an ongoing challenge.

PMID- 25778772
TI  - Re: 'Protective Effect of Focal Adhesion Kinase against Skeletal Muscle
      Reperfusion Injury after Acute Limb Ischemia': Exciting Questions about Ischemia
      Reperfusion Injury.

PMID- 25778773
TI  - Prospective study of the occurrence of psychological disorders and comorbidities
      after spinal cord injury.
AB  - OBJECTIVE: To conduct a prospective study of the occurrence of psychological
      disorders and comorbidities after spinal cord injury (SCI), determine
      psychotropic medication usage, and establish predictors of psychological
      disorders after transition to the community. DESIGN: Longitudinal design with
      multiple measures. SETTING: Assessment occurred in SCI units and the community.
      PARTICIPANTS: Adults with SCI (N=88) admitted over a period of 32 months into 3
      SCI units. INTERVENTIONS: Participants completed inpatient rehabilitation for an
      acute SCI. Longitudinal assessment occurred up to 6 months postdischarge. MAIN
      OUTCOME MEASURES: Measures were chosen that had a theoretical and clinical
      foundation for contributing to recovery after SCI. The Mini International
      Neuropsychiatric Interview, a structured diagnostic psychiatric interview, was
      conducted to determine the presence of psychological disorders. Medical measures
      included severity of secondary conditions or complications. Psychological
      measures included measures of anxiety and depressive mood, resilience, pain
      catastrophization, self-efficacy, and cognitive capacity. RESULTS: Rates of
      psychological disorders of 17% to 25% were substantially higher than rates found
      in the Australian community. The occurrence of psychological disorder
      comorbidities was also very high. Anxiety was significantly elevated in those
      with a psychological disorder. Psychotropic medications were prescribed to more
      than 36% of the sample, with most being antidepressants. Factors predictive of
      psychological disorders included years of education, premorbid
      psychiatric/psychological treatment, cognitive impairment, secondary
      complications, resilience, and anxiety. CONCLUSIONS: SCI can have a substantial
      negative impact on mental health that does not change up to 6 months
      postdischarge. Findings suggest a substantial minority experience increased
      psychosocial distress after the injury and after transitioning into the
      community. Additional resources should be invested in improving the mental health
      of adults with SCI.

PMID- 25778774
TI  - Experiences of Cervical Cancer Survivors in Rural Eastern North Carolina: a
      Qualitative Assessment.
AB  - Little qualitative research has been conducted with cervical cancer survivors. We
      sought to understand the experiences of survivors in rural Eastern North Carolina
      and identify any barriers which may have kept women from receiving preventive
      Papanicolaou screenings or follow-up care. We conducted semi-structured in-depth
      interviews with 15 low-income and underserved cervical cancer survivors living in
      Eastern North Carolina. Participants included English-speaking women who attended
      a large cancer center for care between March 2012 and March 2013. Participants
      ranged from being recently diagnosed with cervical cancer to being 15 years post
      diagnosis. Interviews lasted approximately 1 h and were audio-tape-recorded. On
      average, women were 55 years old (range 35-85) and were diagnosed with cervical
      cancer 3 years prior to the interview (range 0.2 to 180 months). A good
      proportion was uninsured or Medicaid-insured (60 %). Half reported an annual
      household income of less than $20,000, and 13 % reported having a college degree.
      The majority of survivors had limited understanding of cervical cancer,
      experienced persistent symptoms related to their cancer before seeking care, and
      were nonadherent to Papanicolaou screening recommendations. The main barriers to
      care reported by participants was lack of money and health insurance, followed by
      the perception of overall health (which equated to the belief that medical care
      was not needed), transportation issues, and discomfort with provider. Health
      professionals should focus educational efforts on the benefits of Papanicolaou
      screenings, the symptoms sometimes associated with cervical cancer, and the free
      or low-cost services available to low-income women.

PMID- 25778775
TI  - Surface plasmon enhanced energy transfer between gold nanorods and fluorophores:
      application to endocytosis study and RNA detection.
AB  - Previously we have demonstrated surface plasmon enhanced energy transfer between
      fluorophores and gold nanorods under two-photon excitation using fluorescence
      lifetime imaging microscopy (FLIM) in both solution and intracellular phases.
      These studies demonstrated that gold nanoparticle-dye energy transfer
      combinations are appealing, not only in Forster resonance energy transfer (FRET)
      imaging, but also energy transfer-based fluorescence lifetime sensing of bio
      analytes. Here, we apply this approach to study the internalization of gold
      nanorods (GNRs) in HeLa cells using the early endosome labeling marker GFP. The
      observed energy transfer between GFP and the GNRs indicates the involvement of
      endocytosis in GNR uptake. Moreover, a novel nanoprobe based on oligonucleotide
      functionalized gold nanorods for nucleic acid sensing via dye-GNRs energy
      transfer is demonstrated, potentially opening up new possibilities in cancer
      diagnosis and prognosis. The influence of oligonucleotide design on such
      nanoprobe performance was studied for the first time using time-resolved
      fluorescence spectroscopy, bringing new insights to the optimization of the
      nanoprobe. 

PMID- 25778777
TI  - Evidence of climate-driven ecosystem reorganization in the Gulf of Mexico.
AB  - The Gulf of Mexico is one of the most ecologically and economically valuable
      marine ecosystems in the world and is affected by a variety of natural and
      anthropogenic phenomena including climate, hurricanes, coastal development,
      agricultural runoff, oil spills, and fishing. These complex and interacting
      stressors, together with the highly dynamic nature of this ecosystem, present
      challenges for the effective management of its resources. We analyze a
      compilation of over 100 indicators representing physical, biological, and
      economic aspects of the Gulf of Mexico and find that an ecosystem-wide
      reorganization occurred in the mid-1990s. Further analysis of fishery landings
      composition data indicates a major shift in the late 1970s coincident with the
      advent of US national fisheries management policy, as well as significant shifts
      in the mid-1960s and the mid-1990s. These latter shifts are aligned temporally
      with changes in a major climate mode in the Atlantic Ocean: the Atlantic
      Multidecadal Oscillation (AMO). We provide an explanation for how the AMO may
      drive physical changes in the Gulf of Mexico, thus altering higher-level
      ecosystem dynamics. The hypotheses presented here should provide focus for
      further targeted studies, particularly in regard to whether and how management
      should adjust to different climate regimes or states of nature. Our study
      highlights the challenges in understanding the effects of climatic drivers
      against a background of multiple anthropogenic pressures, particularly in a
      system where these forces interact in complex and nonlinear ways.

PMID- 25778776
TI  - Effects of prenatal cocaine exposure on adolescent development.
AB  - The associations between prenatal cocaine exposure (PCE) and adolescent behavior,
      cognitive development, and physical growth were examined in 219 15-year-olds who
      have participated in a longitudinal study since their fourth gestational month.
      During the first trimester, 42% of the women used cocaine, with use declining
      across pregnancy. At the 15-year follow-up, the caregivers were, on average, 43
      years old, had 13 years of education, and 50% were African American. First
      trimester PCE was not associated with global cognitive development or with
      measures of learning and memory. First trimester PCE was significantly related to
      adolescent-reported delinquent behavior, poorer problem solving and abstract
      reasoning, and reduced weight, height, and head circumference at 15 years. These
      results were significant after other factors that affect these domains were
      controlled in regression analyses. In addition, exposure to violence partially
      mediated the effect of PCE on delinquent behavior. These adolescent domains are
      important because they are predictors of poorer adult functioning.

PMID- 25778778
TI  - Lack of replication for the myosin-18B association with mathematical ability in
      independent cohorts.
AB  - Twin studies indicate that dyscalculia (or mathematical disability) is caused
      partly by a genetic component, which is yet to be understood at the molecular
      level. Recently, a coding variant (rs133885) in the myosin-18B gene was shown to
      be associated with mathematical abilities with a specific effect among children
      with dyslexia. This association represents one of the most significant genetic
      associations reported to date for mathematical abilities and the only one
      reaching genome-wide statistical significance. We conducted a replication study
      in different cohorts to assess the effect of rs133885 maths-related measures. The
      study was conducted primarily using the Avon Longitudinal Study of Parents and
      Children (ALSPAC), (N = 3819). We tested additional cohorts including the York
      Cohort, the Specific Language Impairment Consortium (SLIC) cohort and the Raine
      Cohort, and stratified them for a definition of dyslexia whenever possible. We
      did not observe any associations between rs133885 in myosin-18B and mathematical
      abilities among individuals with dyslexia or in the general population. Our
      results suggest that the myosin-18B variant is unlikely to be a main factor
      contributing to mathematical abilities. 

PMID- 25778780
TI  - Oxytocin and empathy to pain in schizophrenia: a reply.

PMID- 25778779
TI  - Fine-scale analysis of 16S rRNA sequences reveals a high level of taxonomic
      diversity among vaginal Atopobium spp.
AB  - Although vaginal microbial communities of some healthy women have high
      proportions of Atopobium vaginae, the genus Atopobium is more commonly associated
      with bacterial vaginosis, a syndrome associated with an increased risk of adverse
      pregnancy outcomes and the transmission of sexually transmitted diseases. Genetic
      differences within Atopobium species may explain why single species can be
      associated with both health and disease. We used 16S rRNA gene sequences from
      previously published studies to explore the taxonomic diversity of the genus
      Atopobium in vaginal microbial communities of healthy women. Although A. vaginae
      was the species most commonly found, we also observed three other Atopobium
      species in the vaginal microbiota, one of which, A. parvulum, was not previously
      known to reside in the human vagina. Furthermore, we found several potential
      novel species of the genus Atopobium and multiple phylogenetic clades of A.
      vaginae. The diversity of Atopobium found in our study, which focused only on
      samples from healthy women, is greater than previously recognized, suggesting
      that analysis of samples from women with BV would yield even more diversity.
      Classification of microbes only to the genus level may thus obfuscate differences
      that might be important to better understand health or disease. 

PMID- 25778781
TI  - Blocking M2 muscarinic receptor signaling inhibits tumor growth and reverses
      epithelial-mesenchymal transition (EMT) in non-small cell lung cancer (NSCLC).
AB  - Lung cancers express non-neuronal, cholinergic autoparacrine loop, which
      facilitates tumor growth. Interruption of M3 muscarinic cholinergic signaling has
      been reported to inhibit small cell lung cancer (SCLC) growth. The purpose of
      this study is to investigate if blocking autoparacrine muscarinic cholinergic
      signaling could inhibit non-small cell lung cancer (NSCLC) growth and possible
      underlying mechanisms. Our results showed that PC9 and A549 cells expressed all 5
      subtypes of muscarinic receptor (mAChR) and blocking M2 mAChR (M2R) signaling
      using selective antagonist methoctramine or short hairpin RNA (shRNA) inhibited
      tumor cell proliferation in vitro and in vivo. Consistent with AChR agonists
      stimulating p44/42 MAPK (Erk1/2) and Akt phosphorylation, blocking M2R signaling
      decreased MAPK and Akt phosphorylation, indicating that non-neuronal ACh
      functions as an autoparacrine growth factor signaling in part through activation
      of M2R and downstream MAPK and Akt pathways. Importantly, further studies
      revealed that blocking M2R signaling also reversed epithelial-mesenchymal
      transition (EMT) in vitro and in vivo, indicating that non-neuronal ACh promotes
      EMT partially through activation of M2R. These findings demonstrate that M2R
      plays a role in the growth and progression of NSCLC and suggest M2R antagonists
      may be an efficacious adjuvant therapy for NSCLC. 

PMID- 25778782
TI  - Neuroprotective effect of loganin against Abeta25-35-induced injury via the NF
      kappaB-dependent signaling pathway in PC12 cells.
AB  - Amyloid-beta (Abeta) protein, the main constituent of senile plaques, is believed
      to play a pivotal role in the pathogenesis of Alzheimer's disease (AD). AD is
      closely associated with inflammatory reactions which are considered to be
      responses to Abeta deposition. The present study investigated the effect of
      loganin on Abeta25-35-induced inflammatory damage and the underlying molecular
      mechanism of its neuroprotective action. Loganin predominantly prevented Abeta25
      35-stimulated cell death through suppressing ROS generation, and attenuating
      apoptosis by inhibiting caspase-3 activity and regulating cell cycle.
      Furthermore, loganin suppressed the level of TNF-alpha and protein expression of
      iNOS and COX-2 in Abeta25-35-injured PC12 cells. These inhibitions appeared to
      correlate with the suppression of NF-kappaB activation by loganin, as pre
      treating cells with loganin blocked the translocation of NF-kappaB into the
      nuclear compartment and degradation of the inhibitory subunit IkappaB. Loganin
      substantially inhibited phosphorylation of MAPKs including ERK1/2, p38 and JNK,
      which are closely related to regulation of NF-kappaB activation. Taken together,
      the results implied that loganin attenuated neuroinflammatory responses through
      the inactivation of NF-kappaB by NF-kappaB dependent inflammatory pathways and
      phosphorylation of MAPK in Abeta25-35-induced PC12 cells. 

PMID- 25778783
TI  - Prospective cohort study on the outcomes of hepatitis C virus-related cirrhosis
      in South Korea.
AB  - BACKGROUND AND AIMS: The outcomes of hepatitis C virus (HCV)-related liver
      cirrhosis was limitedly studied in a hepatitis B virus-endemic area. This
      multicenter, prospective cohort study was conducted to elucidate the incidence of
      hepatocellular carcinoma (HCC) and mortality in the Korean patients with HCV
      related cirrhosis. METHODS: From January 2007 through June 2012, 196 patients
      with HCV-related cirrhosis were prospectively enrolled and regularly followed at
      six university hospitals to determine HCC occurrence and mortality. A
      multivariable analysis using Cox proportional hazards regression was performed to
      clarify the related factors to the outcomes. RESULTS: During a mean follow-up
      period of 39.2 months, 31 (15.8%) patients developed HCC, and 33 (16.8%) patients
      died or underwent liver transplantation. The estimated HCC incidence was 5.8 per
      100 person-years, and the independent factors for HCC were absence of anti-HBV
      surface antibody (HBs hazard ratio [HR], 5.018; 95% confidence interval [CI],
      1.710-14.726; P = 0.003) and serum albumin < 3.8 g/dL (HR, 3.051; 95% CI, 1.318
      7.067; P = 0.009). The overall mortality rate was 5.1 per 100 person-years, and
      the related independent factors were the presence of ascites (HR, 2.448; 95% CI,
      1.142-5.210; P = 0.022), serum albumin < 3.8 g/dL (HR, 3.067; 95% CI, 1.254
      8.139, P = 0.014), and nonachievement of sustained virologic response (SVR) (HR,
      0.066; 95% CI, 0.001-0.484, P = 0.002). CONCLUSION: The incidence of HCC in HCV
      related cirrhosis seems to be high in Korea, and advanced liver disease and no
      achievement of SVR were associated with mortality. The absence of anti-HBs in
      hepatocarcinogenesis related to HCV warrants further study.

PMID- 25778784
TI  - Copper nanocrystal plane effect on stereoselectivity of catalytic deoxygenation
      of aromatic epoxides.
AB  - Previous studies have shown that crystal planes of heterogeneous catalysts could
      display enhanced activity, such that higher turnover or chemoselectivity could be
      achieved. Here we report an example where the reaction stereoselectivity was
      significantly affected by the catalyst crystal planes. In copper-catalyzed
      deoxygenation reaction of aromatic epoxides, copper cubes, wires, and plates gave
      the olefin products with different cis/trans selectivities, whereas homogeneous
      copper catalysts showed poor selectivity. Scanning tunneling microscope and
      density functional theory studies revealed that the different adsorption mode and
      higher adsorption strength of epoxide oxygen on Cu{100} plane were responsible
      for the observed variation of selectivity. The copper-catalyzed deoxygenation
      reaction provided new practical access to cis-olefins from readily available
      aromatic epoxides. Our work also indicated that nanocrystal catalysts may provide
      useful stereochemical control in organic reactions. 

PMID- 25778785
TI  - Trek1 contributes to maintaining nasal epithelial barrier integrity.
AB  - Epithelial barrier integrity is critical to maintain the homeostasis in the body.
      The regulatory mechanism of the epithelial barrier function has not been fully
      understood. This study aims to elucidate the role of the TWIK-related potassium
      channel-1 (Trek1) in the regulation of the epithelial barrier function of the
      nasal mucosa. In this study, the levels of Trek1 were assessed by real time RT
      PCR and Western blotting. The epithelial barrier function of the rat nasal
      epithelia was evaluated by the Ussing chamber system. The results showed that
      Trek1 was detected in the human and rat nasal epithelia, which were significantly
      lower in patients and rats with allergic rhinitis than that in healthy controls.
      Exposure to the signature T helper 2 cytokine, interleukin (IL)-4, markedly
      suppressed the expression of Trek1 in the nasal mucosa via up regulating the
      expression of the histone deacetylase (HDAC)1. The IL-4-induced rat nasal
      epithelial barrier dysfunction could be blocked by HDAC1 inhibitor (Trichostatin
      A), or sodium butyrate, or administration of Clostridium Butyricum. We conclude
      that Trek1 is critical to maintain the nasal epithelial barrier function. 

PMID- 25778786
TI  - Organocatalytic atroposelective formal Diels-Alder desymmetrization of N
      arylmaleimides.
AB  - The atroposelective desymmetrization of N-arylmaleimides was realized by means of
      a primary amine catalyzed Diels-Alder reaction of enones. The chiral axis as new
      element of chirality is generated under the remote control of the catalyst that
      selectively drives the formal Diels-Alder reaction through an exclusive
      stereochemical outcome. 

PMID- 25778787
TI  - Folic acid significantly reduces risk of first stroke, large Chinese study finds.

PMID- 25778788
TI  - Carry on winning: no selection effect.
AB  - The methods proposed by Demaree, Weaver and Juergensen (2014) are not the most
      appropriate for testing for the presence of a selection effect. We use a simple
      and straightforward method to demonstrate that the data are not consistent with
      such an effect. 

PMID- 25778789
TI  - Shubnikov-de Haas oscillations, weak antilocalization effect and large linear
      magnetoresistance in the putative topological superconductor LuPdBi.
AB  - We present electronic transport and magnetic properties of single crystals of
      semimetallic half-Heusler phase LuPdBi, having theoretically predicted band
      inversion requisite for nontrivial topological properties. The compound exhibits
      superconductivity below a critical temperature Tc = 1.8 K, with a zero
      temperature upper critical field Bc2 ~ 2.3 T. Although superconducting state is
      clearly reflected in the electrical resistivity and magnetic susceptibility data,
      no corresponding anomaly can be seen in the specific heat. Temperature dependence
      of the electrical resistivity suggests existence of two parallel conduction
      channels: metallic and semiconducting, with the latter making negligible
      contribution at low temperatures. The magnetoresistance is huge and clearly shows
      a weak antilocalization effect in small magnetic fields. Above about 1.5 T, the
      magnetoresistance becomes linear and does not saturate in fields up to 9 T. The
      linear magnetoresistance is observed up to room temperature. Below 10 K, it is
      accompanied by Shubnikov-de Haas oscillations. Their analysis reveals charge
      carriers with effective mass of 0.06 me and a Berry phase very close to pi,
      expected for Dirac-fermion surface states, thus corroborating topological nature
      of the material.

PMID- 25778790
TI  - A photoinduced growth system of peptide nanofibres addressed by DNA
      hybridization.
AB  - Spatiotemporal control of peptide nanofibre growth was achieved by photocleavage
      of a DNA-conjugated beta-sheet forming peptide that is linked through a
      photoresponsive amino acid residue. Peptide nanofibres were selectively formed by
      photocleaving the conjugate on a complementary DNA-immobilised glass substrate. 

PMID- 25778791
TI  - Chronic rhinosinusitis and cystic fibrosis: the interaction between sinus
      bacteria and mucosal immunity.
AB  - BACKGROUND: Chronic rhinosinusitis (CRS) is highly prevalent in cystic fibrosis
      (CF) patients, in whom a close correlation exists between the microbiology of the
      upper and lower respiratory tracts. We have reported intramucosal bacterial
      microcolonies in the sinus mucosa from idiopathic CRS patients and have made
      observations suggesting that these may result from mucosal immunotolerance
      secondary to altered macrophage function. In this study, we sought to determine
      whether intramucosal microcolonies exist in the mucosa of CF patients with CRS,
      and to investigate the associated mucosal immunology. METHODS: Mucus swabs and
      tissue biopsies were taken from 9 patients with CF undergoing functional
      endoscopic sinus surgery (FESS) for CRS, 11 with idiopathic CRS undergoing FESS,
      and 9 with normal sinuses having transnasal pituitary surgery. Microbiology
      samples were taken for culture and intramucosal microcolonies were sought using
      Gram staining. Mucosal immune cells were identified using fluorescent
      immunohistochemistry. RESULTS: Positive culture rates were similar between CRS
      patients and controls, but there were significantly more intramucosal
      microcolonies in the CRS groups (8/9 CF-CRS, 7/11 CRS), compared to controls
      (1/9). Furthermore, the biodensity of intramucosal microcolonies was
      significantly higher in CF-CRS than idiopathic CRS. Mirroring the microbiological
      observations, the number of CD163+ macrophages was significantly increased in CF
      CRS compared to idiopathic CRS (p = 0.03). CONCLUSION: Intramucosal bacteria
      exist within the sinus mucosa of patients with CF, and in significantly greater
      numbers than in idiopathic CRS patients. We speculate that intramucosal
      microcolonies may also exist in the lower respiratory tract mucosa in CF and play
      a role in disease recalcitrance.

PMID- 25778792
TI  - Response to correspondence: An immunohistochemical study of potential diagnostic
      and therapeutic biomarkers of wild-type gastrointestinal stromal tumours.

PMID- 25778793
TI  - The immunosuppressive enzyme IL4I1 promotes FoxP3(+) regulatory T lymphocyte
      differentiation.
AB  - IL4I1 (interleukin-4-induced gene 1) is a phenylalanine oxidase produced mainly
      by APCs of myeloid origin, and converts phenylalanine (Phe) to phenylpyruvate,
      hydrogen peroxide, and ammonia. We have previously shown that IL4I1 is highly
      expressed by tumor-associated macrophages from various human cancers and
      facilitates immune evasion from the cytotoxic response in a murine tumor model.
      Indeed, IL4I1 inhibits T-cell proliferation via hydrogen peroxide toxicity on
      effector/memory T cells. Here, we explored the effect of IL4I1 on naive CD4(+) T
      cell differentiation. We show that IL4I1 stimulates the generation of Foxp3(+)
      regulatory T (Treg) cells in vitro from human and mouse T cells. This effect was
      observed with IL4I1 from different sources, including the naturally produced
      enzyme. Conversely, IL4I1 limits Th1 and Th2 polarization while modifying the
      Th17 phenotype, in particular, by inducing its own production. Analysis of Treg
      cell induction under conditions of Phe deprivation and hydrogen peroxide addition
      suggests that Phe consumption by the enzyme participates in Treg-cell enrichment.
      In line with this hypothesis, IL4I1 inhibits mTORC1 signaling shortly after T
      cell activation. Thus, the IL4I1 enzyme may act on T cells both by direct
      inhibition of effector cell proliferation and by indirect immunoregulation
      mediated by Treg-cell induction. 

PMID- 25778794
TI  - Determination of pharmaceuticals in bivalves using QuEChERS extraction and liquid
      chromatography-tandem mass spectrometry.
AB  - A method for the quantitative determination of seven pharmaceuticals in bivalves
      was developed by QuEChERS (Quick, Easy, Cheap, Effective, Rugged and Safe)
      extraction, followed by liquid chromatography-tandem mass spectrometry (LC-MS/MS)
      with electrospray ionization. Both the European Standard Method EN 15662 and the
      AOAC Official Method 2007.01 for QuEChERS were tested. In addition, several clean
      up strategies were evaluated in order to clean the matrix previous to the LC
      MS/MS analyses. Dispersive solid-phase extraction with silica gel and
      modification of the chromatographic separation were the clean-up strategies that
      gave the best results. The optimized method was validated in mussels (Mytilus
      galloprovincialis) and allowed the determination of pharmaceuticals at nanograms
      per gram levels (dry weight (d.w.)). Limits of quantification ranged from 5 to
      100 ng/g. Apparent recoveries ranged from 35 to 77%. The application of this
      method to bivalves revealed the presence of salicylic acid at concentrations up
      to 103 ng/g (d.w.).

PMID- 25778796
TI  - Developing a fidelity assessment instrument for nurse home visitors.
AB  - Fidelity monitoring is a core component for successful translation of evidence
      based interventions, yet little guidance is available on developing tools to
      assess intervention fidelity that are valid and feasible for use in community
      settings. We partnered with nurses in the field to develop a fidelity monitoring
      instrument that would capture the essential elements of the nursing intervention
      that is the core of Nurse-Family Partnership, a prenatal and early childhood home
      visitation program. Using a grounded approach, we employed concept mapping to
      identify the salient behavioral characteristics associated with the program, and
      then, adapting Dreyfus' model of skill development, created a tool to assess
      nurse home visitors (NHVs) according to their stage of growth. In a pilot, the
      Nursing Practice Assessment (NPA) form was used to assess 188 NHVs. The average
      time to complete the tool was 1 hour, and skill development stage was concordant
      with years of NHV experience. According to surveys of supervisors and NHVs, the
      tool captured the essential elements of the program model. Articulating the
      essential elements of each skill development stage can provide a foundation for
      professional development for NHVs. In response to feedback, online training
      modules were developed prior to large-scale implementation in the field. The
      grounded methods used to develop the NPA enhanced its internal consistency and
      implementation feasibility and could be utilized by other public health nursing
      programs.

PMID- 25778795
TI  - Sociodemographic disparities in differentiated thyroid cancer survival among
      adolescents and young adults in California.
AB  - BACKGROUND: Few studies have focused on prognostic factors among adolescents and
      young adults (AYAs) 15 to 39 years of age when diagnosed with differentiated
      thyroid cancer (DTC). Our study expands upon prior work by including an
      evaluation of survival among AYA men and by neighborhood socioeconomic status,
      health insurance, and clinical factors to identify subgroups of young DTC
      patients at higher risk of mortality. METHODS: Data for 16,827 AYA DTC patients
      diagnosed between 1988 and 2010 were obtained from the California Cancer
      Registry. Survival, through 2010, by sociodemographic and clinical factors was
      analyzed using Cox proportional hazards regression. RESULTS: Of the 2.1% of AYAs
      who died, 16.7% died from thyroid cancer and 21.4% died from a subsequent cancer.
      In multivariate analyses, older AYAs 35 to 39 year of age (versus 15- to 29-year
      olds), men (hazard ratio [HR] 2.77, 95% confidence interval [CI] 1.62-4.72), and
      AYAs of African American or Hispanic race/ethnicity (versus non-Hispanic whites)
      had worse thyroid cancer specific survival. In addition, residing in low
      socioeconomic status neighborhoods (HR 3.11 [CI 1.28-7.56]) and nonmetropolitan
      areas (HR 5.53 [CI 2.07-14.78]) was associated with worse thyroid cancer-specific
      survival among AYA men, but not AYA women. CONCLUSIONS: Despite the generally
      good prognosis among AYAs with DTC, we identified subgroups of AYA patients at
      risk for poor outcomes. Further study of the factors underlying these
      associations, including possible barriers to receiving high-quality treatment and
      follow-up care, as well as lifestyle factors, are critical to reducing these
      disparities.

PMID- 25778797
TI  - Authors' response.

PMID- 25778798
TI  - A causal model for longitudinal randomised trials with time-dependent non
      compliance.
AB  - In the presence of non-compliance, conventional analysis by intention-to-treat
      provides an unbiased comparison of treatment policies but typically under
      estimates treatment efficacy. With all-or-nothing compliance, efficacy may be
      specified as the complier-average causal effect (CACE), where compliers are those
      who receive intervention if and only if randomised to it. We extend the CACE
      approach to model longitudinal data with time-dependent non-compliance, focusing
      on the situation in which those randomised to control may receive treatment and
      allowing treatment effects to vary arbitrarily over time. Defining compliance
      type to be the time of surgical intervention if randomised to control, so that
      compliers are patients who would not have received treatment at all if they had
      been randomised to control, we construct a causal model for the multivariate
      outcome conditional on compliance type and randomised arm. This model is applied
      to the trial of alternative regimens for glue ear treatment evaluating surgical
      interventions in childhood ear disease, where outcomes are measured over five
      time points, and receipt of surgical intervention in the control arm may occur at
      any time. We fit the models using Markov chain Monte Carlo methods to obtain
      estimates of the CACE at successive times after receiving the intervention. In
      this trial, over a half of those randomised to control eventually receive
      intervention. We find that surgery is more beneficial than control at 6months,
      with a small but non-significant beneficial effect at 12months.

PMID- 25778800
TI  - Analysis of gene expression of bifidobacteria using as the reporter an anaerobic
      fluorescent protein.
AB  - OBJECTIVES: To determine the effectiveness of evoglow-Pp1 as a reporter to study
      gene expression in bifidobacteria. To choose a strong and constitutive promoter
      to track fluorescently labelled bifidobacteria in environments under anaerobic
      conditions. RESULTS: The elongation factor P (EF-P) promoter from Bifidobacterium
      longum CECT 4551 produced the highest emission of fluorescence signal and was
      therefore able to produce the highest gene expression of the promoters studied.
      The promoters from B. longum CECT 4551 showed different fluorescence signal
      intensities which, in descending order, were: EF-P, initiation factor IF-2,
      elongation factor G, elongation factor Tu, elongation factor Nus A, elongation
      factor Ts and 30S ribosomal protein S12. CONCLUSIONS: The consistency of the
      methods employed (fluorescence imaging system, fluorescence microscopy,
      fluorimetry and flow cytometry) showed that the construction pNZ:Prom.GFPana
      contained the anaerobic fluorescent protein evoglow-Pp1 could be exploited as a
      tool for analysing the gene expression in bifidobacteria strains.

PMID- 25778799
TI  - Fc gamma receptor IIb participates in maternal IgG trafficking of human placental
      endothelial cells.
AB  - The human placental transfer of maternal IgG is crucial for fetal and newborn
      immunity. Low-affinity immunoglobulin gamma Fc region receptor IIb2 (FCGR2B2 or
      FcgammaRIIb2) is exclusively expressed in an IgG-containing, vesicle-like
      organelle (the FCGR2B2 compartment) in human placental endothelial cells; thus,
      we hypothesized that the FCGR2B2 compartment functions as an IgG transporter. In
      this study, to examine this hypothesis, we performed in vitro bio-imaging
      analysis of IgG trafficking by FCGR2B2 compartments using human umbilical vein
      endothelial cells transfected with a plasmid vector containing enhanced GFP
      tagged FCGR2B2 (pFCGR2B2-EGFP). FCGR2B2-EGFP signals were detected as
      intracellular vesicular structures similar to FCGR2B2 compartments in vivo. The
      internalization and transcytosis of IgG was significantly higher in the pFCGR2B2
      EGFP-transfected cells than in the mock-transfected cells, and the majority of
      the internalized IgG was co-localized with the FCGR2B2-EGFP signals. Furthermore,
      we isolated FCGR2B2 compartments from the human placenta and found that the Rab
      family of proteins [RAS-related protein Rab family (RABs)] were associated with
      FCGR2B2 compartments. Among the RABs, RAB3D was expressed predominantly in
      placental endothelial cells. The downregulation of RAB3D by small interfering RNA
      (siRNA) resulted in a marked reduction in the FCGR2B2-EGFP signals at the cell
      periphery. Taken together, these findings suggest that FCGR2B2 compartments
      participate in the transcytosis of maternal IgG across the human placental
      endothelium and that RAB3D plays a role in regulating the intracellular dynamics
      of FCGR2B2 compartments.

PMID- 25778801
TI  - Direct utilization of purple sweet potato by sake yeasts to produce an
      anthocyanin-rich alcoholic beverage.
AB  - OBJECTIVE: To produce an alcoholic beverage containing anthocyanins that can act
      as antioxidants and have anticarcinogenic activities and antihypertensive
      effects. RESULTS: High starch-assimilating sake yeast strain of Saccharomyces
      cerevisiae co-expressing the glucoamylase and alpha-amylase genes from
      Debaryomyces occidentalis using the double rDNA-integration system was developed.
      The new strain grew substantially using 5 % (w/v) purple sweet potato flour as
      the sole carbon source. Its cell yield reached 14.5 mg ml(-1) after 3 days. This
      value was 2.4-fold higher than that of the parental wild-type strain. It produced
      12 % (v/v) ethanol from 20 % (w/v) purple sweet potato flour and consumed 98 % of
      the starch content in purple sweet potato flour after 5 days of fermentation.
      CONCLUSION: We have produced a health-promoting alcoholic beverage abundant in
      anthocyanins from purple sweet potato.

PMID- 25778802
TI  - Square tiling by square macrocycles at the liquid/solid interface: co
      crystallisation with one- or two-dimensional order.
AB  - We have systematically investigated the self-assembled monolayers of seven
      bimolecular mixtures of square-shaped pyridinophanes and cyclophanes bearing
      alkoxy or alkoxycarbonyl substituents in the presence of the tropylium ion as a
      marker of pyridinophanes at liquid/graphite interfaces by means of scanning
      tunnelling microscopy (STM). The purpose of this work was to elucidate the mixing
      behaviour of these macrocycles highlighting the formation of one- or two
      dimensionally ordered square tilings consisting of alternating alignments of
      different macrocycles as a result of attractive dipole-dipole or hydrogen-bonding
      interactions; four co-crystals differing in the dimensionality of the ordering of
      pyridinophane and cyclophane were observed. The different modes of interaction
      between the functional groups (ether or carbonyl group) in the side-chains of the
      pyridinophanes and cyclophanes lead to the formation of co-crystals with
      dimensionally different orderings of the two macrocycles. These observations
      revealed that a slight modification of the molecular structure may dramatically
      change the mixing behaviour and structures of the co-crystals. 

PMID- 25778804
TI  - BiP, From Putting Out Fires to Fanning the Flames in Rheumatoid Arthritis.

PMID- 25778803
TI  - A RIPK2 inhibitor delays NOD signalling events yet prevents inflammatory cytokine
      production.
AB  - Intracellular nucleotide binding and oligomerization domain (NOD) receptors
      recognize antigens including bacterial peptidoglycans and initiate immune
      responses by triggering the production of pro-inflammatory cytokines through
      activating NF-kappaB and MAP kinases. Receptor interacting protein kinase 2
      (RIPK2) is critical for NOD-mediated NF-kappaB activation and cytokine
      production. Here we develop and characterize a selective RIPK2 kinase inhibitor,
      WEHI-345, which delays RIPK2 ubiquitylation and NF-kappaB activation downstream
      of NOD engagement. Despite only delaying NF-kappaB activation on NOD stimulation,
      WEHI-345 prevents cytokine production in vitro and in vivo and ameliorates
      experimental autoimmune encephalomyelitis in mice. Our study highlights the
      importance of the kinase activity of RIPK2 for proper immune responses and
      demonstrates the therapeutic potential of inhibiting RIPK2 in NOD-driven
      inflammatory diseases. 

PMID- 25778817
TI  - Erectile dysfunction post-perineal anastomotic urethroplasty for traumatic
      urethral injuries: analysis of incidence and possibility of recovery.
AB  - PURPOSE: To evaluate the incidence of erectile dysfunction (ED) and
      recoverability of erectile function (EF) after anastomotic urethroplasty for
      traumatic urethral injuries (TUIs) of different etiologies. METHODS: A
      retrospective review for patients' records underwent perineal anastomotic
      urethroplasty for TUIs from June 1998 to January 2014 was conducted. Those
      patients were contacted and evaluated using the International Index of erectile
      function questionnaire in sexually active men, and in unmarried men, the single
      question self-report of ED was used. Patients with ED underwent penile color
      Doppler ultrasonography. RESULTS: Overall, 81 patients were included in the
      study. The incidences of ED following urethroplasty for TUIs were 72.3, 35.3 and
      0% in cases due to pelvic fracture, straddle and iatrogenic injuries,
      respectively. None of the patients reported deterioration of EF after
      urethroplasty. Seven (13.5%) patients reported recovery of their EF within 2
      years after trauma. The probability of recovery of EF after PFUI was 9% compared
      to 28.6 and 100% in patients with straddle and iatrogenic urethral injuries,
      respectively. Patients with type C pelvic fracture had no chance for EF
      recoverability. CONCLUSIONS: PFUIs have a probability of causing ED as much as
      72% compared to 35 and 0% in men with straddle and iatrogenic urethral injuries,
      respectively. Anastomotic urethroplasty has no deleterious effect on EF. A
      tendency for higher recoverability of EF could be observed after iatrogenic
      urethral injuries followed by straddle injury then PFUIs. The probability of
      recovery decreased proportionally with severity of pelvic trauma.

PMID- 25778818
TI  - The comparison of percutaneous ethanol and polidocanol sclerotherapy in the
      management of simple renal cysts.
AB  - OBJECTIVE: To compare the efficacy and safety of percutaneous ethanol and
      polidocanol sclerotherapy in the management of simple renal cysts. MATERIALS AND
      METHODS: Between 2008 and 2013, symptomatic Bosniak type I renal cysts with a
      diameter larger than 5 cm in ultrasonography (US) or computed tomography were
      included in the study and divided into two groups. Group 1 patients were treated
      by US-guided percutaneous polidocanol sclerotherapy, and group 2 patients were
      treated by US-guided percutaneous ethanol sclerotherapy. The pre-operative and
      postoperative US findings were documented to compare the cyst recurrence and the
      reduction in cyst size. Success was defined as complete or partial: as >90%
      reduction or 50-90% reduction in cyst size, respectively. Failure was defined as
      <50% reduction in cyst size. The success rates of two groups were compared.
      Intraoperative pain was assessed using a visual analog scale (VAS) just after the
      operation. RESULTS: The median follow-up period was 36 months (range 12-76) in
      group 1 and 39 months (range 10-78) in group 2. Group 1 consists of 86 patients
      with 89 simple renal cysts, and group 2 consists of 57 patients with 57 simple
      renal cysts. Anatomical success was documented in 49 (55.1%) and 48 (84.2%) cysts
      in groups 1 and 2, respectively (p < 0.001). Clinical success was seen in 56
      (65.1%) and 43 (75.4%) patients in groups 1 and 2, respectively. Major
      complication was detected in only one patient in group 2 (aseptic psoas abscess),
      and there was not any major complication in group 1. Minor complications had
      occurred in ten patients in group 2 (microscopic hematuria in six patients and
      fever and nausea in four patients) and in eight patients in group 1 (microscopic
      hematuria in six patients and fever and nausea in two patients). The mean VAS
      scores were 21 +/- 1.04 and 4.26 +/- 1.99 in ethanol and polidocanol groups,
      respectively (p < 0.001). Ethanol was found to be significantly painful, compared
      to polidocanol in the sclerotherapy of simple renal cysts. CONCLUSIONS: Although
      the complication rates and VAS scores of ethanol sclerotherapy are higher than
      those of polidocanol sclerotherapy, its success rates appear to be also higher.
      The decision of which sclerosing agent will be used should be based on patients'
      comorbidities, cyst location and the surgeon's experience.

PMID- 25778820
TI  - Apoptosis induced by sonodynamic therapy in human osteosarcoma cells in vitro.
AB  - The aim of the present study was to investigate the potential effect of
      hematoporphyrin monomethyl ether-sonodynamic therapy (HMME-SDT) on MG-63
      osteosarcoma cells. The HMME concentration was kept constant at 20 ug/ml and the
      MG-63 osteosarcoma cell line was exposed to ultrasound with an intensity of 1.0
      W/cm2 for 30 sec. Cell cytotoxicity was quantified using an MTT assay 6 h after
      HMME-SDT. The intracellular localization of HMME was imaged using inverted
      confocal laser scanning microscopy. Apoptosis was investigated using flow
      cytometry with Annexin V-fluorescein isothiocyanate and propidium iodine
      staining. The cytotoxicity of HMME-mediated sonodynamic action on MG-63 cells was
      significantly higher than that of other treatments, including ultrasound alone,
      HMME alone and sham treatment. Flow cytometry demonstrated that HMME-SDT action
      markedly enhanced the apoptotic rate of MG-63 cells. The mechanisms of apoptosis
      were analyzed by measuring the protein expression of poly ADP-ribose polymerase
      (PARP), cleaved PARP, procaspase-3, cleaved caspase-3 and cleaved caspase-9. The
      data demonstrated that HMME-SDT action markedly induced the apoptosis of MG-63
      cells.

PMID- 25778821
TI  - A diversity-oriented synthesis strategy enabling the combinatorial-type variation
      of macrocyclic peptidomimetic scaffolds.
AB  - Macrocyclic peptidomimetics are associated with a broad range of biological
      activities. However, despite such potentially valuable properties, the
      macrocyclic peptidomimetic structural class is generally considered as being
      poorly explored within drug discovery. This has been attributed to the lack of
      general methods for producing collections of macrocyclic peptidomimetics with
      high levels of structural, and thus shape, diversity. In particular, there is a
      lack of scaffold diversity in current macrocyclic peptidomimetic libraries;
      indeed, the efficient construction of diverse molecular scaffolds presents a
      formidable general challenge to the synthetic chemist. Herein we describe a new,
      advanced strategy for the diversity-oriented synthesis (DOS) of macrocyclic
      peptidomimetics that enables the combinatorial variation of molecular scaffolds
      (core macrocyclic ring architectures). The generality and robustness of this DOS
      strategy is demonstrated by the step-efficient synthesis of a structurally
      diverse library of over 200 macrocyclic peptidomimetic compounds, each based
      around a distinct molecular scaffold and isolated in milligram quantities, from
      readily available building-blocks. To the best of our knowledge this represents
      an unprecedented level of scaffold diversity in a synthetically derived library
      of macrocyclic peptidomimetics. Cheminformatic analysis indicated that the
      library compounds access regions of chemical space that are distinct from those
      addressed by top-selling brand-name drugs and macrocyclic natural products,
      illustrating the value of our DOS approach to sample regions of chemical space
      underexploited in current drug discovery efforts. An analysis of three
      dimensional molecular shapes illustrated that the DOS library has a relatively
      high level of shape diversity. 

PMID- 25778822
TI  - Expression of the Olig gene family in the developing mouse inner ear.
AB  - Transcription factors are believed to play key roles in determining cell fate in
      inner ear development. Olig genes, which are basic helix-loop-helix transcription
      factors, have been reported to play important roles in the development of the
      central nervous system. However, members of this family have not previously been
      implicated in inner ear development, despite the similarity between otocyst and
      neural tube development. Olig1 begins to be expressed at the ventral domain of
      the otocyst at embryonic day (E) 9.5, and Olig1 expression in the epithelium of
      the developing inner ear persists to E15.5. Olig2 expression is localized to the
      cochleovestibular ganglia from E12.5 through E14.5. Olig3 has a diffuse
      expression pattern in the developing inner ear from E12.5 through the postnatal
      stage. Furthermore, at early stages of inner ear development, the Olig1
      expression domain overlaps a region that is positive for Sox2 and Jagged1. This
      observation indicates that Olig1 may play an important role in the specification
      of the prosensory domain in the developing inner ear. As Olig genes are expressed
      in the mouse developing inner ear in a temporospatially distinct fashion, they
      may play substantial roles in the regulation of mammalian inner ear development. 

PMID- 25778823
TI  - Manganese transport disorder: novel SLC30A10 mutations and early phenotypes.
AB  - BACKGROUND: SLC30A10 mutations cause an autosomal recessive disorder,
      characterized by hypermanganesaemia, polycythemia, early-onset dystonia,
      paraparesis, or late-onset parkinsonism, and chronic liver disease. This is the
      first identified inborn error of Mn metabolism in humans, reported in 10 families
      thus far. METHODS: Methods for this study consisted of clinical examination,
      neuroimaging studies (MRI), serum dosages, and SLC30A10 genetic analysis.
      RESULTS: We describe early disease manifestations (including videos) in 5
      previously unreported Indian children, carrying novel homozygous SLC30A10
      mutations. Gait and speech disturbances, falls, dystonias, and central hypotonia
      were the presenting neurological features, starting within the first 5 years of
      life. All children also had severe hypermanganesemia, polycythemia, variable
      degree of liver disease, and marked brain MRI T1 hyperintensities. CONCLUSIONS:
      Our findings expand the mutational and clinical spectra of this recently
      recognized disorder. An early diagnosis is warranted, because treatment with
      manganese-chelating agents, iron supplementation, or their combination might
      improve symptoms and prevent progression of this otherwise potentially fatal
      disease. (c) 2015 International Parkinson and Movement Disorder Society.

PMID- 25778824
TI  - Varying RGD concentration and cell phenotype alters the expression of
      extracellular matrix genes in vocal fold fibroblasts.
AB  - The impact of RGD integrin binding-peptide concentration and cell phenotype on
      directing extracellular matrix (ECM) gene expression in vocal fold fibroblasts is
      little understood. Less is known about cell response to RGD concentration on a
      biomaterial when fibroblasts are in a scar-like environment compared to a healthy
      environment. We investigated the effects of varying RGD integrin-binding peptide
      surface concentration on ECM gene expression of elastin, collagen type 3 alpha 1,
      decorin, fibronectin, hyaluronan synthase 2, and collagen type 1 alpha 2 in
      scarred and unscarred immortalized human vocal fold fibroblasts (I-HVFFs).
      Phenotype and RGD concentration affected ECM gene expression. Phenotype change
      from healthy to myofibroblast-like resulted in ECM gene up-regulation for all
      genes tested, except for decorin. Systematically altering RGD concentration
      affected the expression of elastin and collagen type 3 alpha 1 in a myofibroblast
      phenotype. Specifically greater up-regulation in gene expression was observed
      with higher RGD concentrations. This research demonstrates that controlling RGD
      concentration may influence ECM gene expression levels in fibroblasts. Such
      knowledge is critical in developing the next generation of bioactive materials
      that, when implanted into sites of tissue damage and scarring, will direct cells
      to regenerate healthy tissues with normal ECM ratios and morphologies.

PMID- 25778825
TI  - Effects of honey on oral mucositis in patients with head and neck cancer: A meta
      analysis.
AB  - OBJECTIVES/HYPOTHESIS: The objective of this study was to perform a meta-analysis
      of the efficacy of honey in the management of oral mucositis during radiotherapy
      in patients with head and neck cancer. STUDY DESIGN: Meta-analysis using MEDLINE,
      Scopus, and the Cochrane Library as data sources. METHODS: Two authors
      independently searched the databases for relevant studies from inception to June
      2014. Included in the meta-analysis were randomized controlled studies published
      in English comparing the oral administration of honey (honey group) with placebo
      or no treatment (control group) in patients with head and neck cancer who were
      undergoing radiotherapy or chemoradiotherapy. Excluded studies failed to report
      quantifiable outcome measures regarding oral mucositis. Outcomes of interest
      included the degree and incidence of mucositis, incidence of microbial
      colonization, and weight loss. RESULTS: Nine studies comprising 476 patients were
      included in the meta-analysis. The incidence of moderate to severe mucositis and
      the mean mucositis grade during the first 3 weeks of therapy were significantly
      lower in the honey group than the control group. Additionally, the onset of
      mucositis was significantly later in the honey group than the control. Although
      there were no significant differences in the incidences of microbial colonization
      and pain experienced between the two groups, the incidence of weight loss was
      significantly lower in the honey group than control group. CONCLUSIONS: Oral
      administration of honey after radiotherapy could prevent moderate to severe
      mucositis and associated weight loss. However, because our results were based on
      an analysis of a small number of trials, further trials are required to confirm
      these results. LEVEL OF EVIDENCE: NA.

PMID- 25778826
TI  - Living donor liver transplantation using a left liver extended to right anterior
      sector.
AB  - In living donor liver transplantations, right liver grafts have been commonly
      used to meet the metabolic demands of the recipient. However, a small left
      remnant liver volume sometimes limits its use due to donor safety concerns. Here,
      we report an innovative living donor hepatectomy using a left liver extended to
      the right anterior sector (segments 2-5 and 8), which can be considered for
      donors who are unsuited for right liver donation. 

PMID- 25778827
TI  - Effects of Enhanced UV-B Radiation on Biochemical Traits in Postharvest Flowers
      of Medicinal Chrysanthemum.
AB  - This article reported UV-B radiation effects on biochemical traits in postharvest
      flowers of chrysanthemum. The experiment included six levels of UV-B radiation
      (UV0, 0 MUW cm(-2); UV50, 50 MUW cm(-2); UV200, 200 MUW cm(-2); UV400, 400 MUW
      cm(-2); UV600, 600 MUW cm(-2) and UV800, 800 MUW cm(-2). Enhanced UV-B radiation
      significantly increased hydrogen peroxide content (except for UV50), but did not
      evidently affect malondialdehyde content in flowers. Chlorophyll b and total
      chlorophyll content were significantly increased by UV600 and UV800. UV400 and
      UV600 significantly increased anthocyanins, carotenoids and UV-B absorbing
      compounds content, and the activities of phenylalanine ammonia lyase (PAL) and
      cinnamic acid-4-hydroxylase (C4H) over the control. 4-coumarate CoA ligase (4CL)
      activity was significantly decreased by enhanced UV-B radiation (except for
      UV50). The relationships between UV-B radiation intensities and the activities of
      secondary metabolism enzymes were best described by a second-order polynomial.
      The R(2) values for UV-B radiation intensities and the activities of PAL, C4H and
      4CL were 0.8361, 0.5437 and 0.8025, respectively. The results indicated that
      enhanced UV-B radiation could promote secondary metabolism processes in
      postharvest flowers, which might be beneficial for the accumulation of medically
      active ingredients in medicinal plants. The optimal UV-B radiation intensities in
      the study were between UV400-UV600.

PMID- 25778829
TI  - Non-invasive assessment of liver fibrosis: reduce or substitute the need for
      liver biopsy?

PMID- 25778830
TI  - A history of bovine tuberculosis eradication policy in Northern Ireland.
AB  - Despite many years of state-sponsored efforts to eradicate the disease from
      cattle through testing and slaughter, bovine tuberculosis (bTB) is still regarded
      as the most important and complex of animal health challenges facing the British
      livestock agricultural industry. This paper provides a historical analysis of the
      ongoing bTB statutory eradication programme in one part of the UK - Northern
      Ireland (NI) - which began in 1949 as a voluntary scheme, but between 1959 and
      1960 became compulsory for all cattle herd-owners. Tracing bTB back through time
      sets the eradication efforts of the present day within a deeper context, and
      provides signposts for what developed in subsequent decades. The findings are
      based primarily on empirical research using historical published reports of the
      Ministry of Agriculture and state documents held in the public archives in NI,
      and they emphasize the need to consider the economic, social and political
      contexts of disease eradication efforts and their influences on both the past and
      the present. 

PMID- 25778831
TI  - Navigating through metaproteomics data: a logbook of database searching.
AB  - Metaproteomic research involves various computational challenges during the
      identification of fragmentation spectra acquired from the proteome of a complex
      microbiome. These issues are manifold and range from the construction of
      customized sequence databases, the optimal setting of search parameters to
      limitations in the identification search algorithms themselves. In order to
      assess the importance of these individual factors, we studied the effect of
      strategies to combine different search algorithms, explored the influence of
      chosen database search settings, and investigated the impact of the size of the
      protein sequence database used for identification. Furthermore, we applied de
      novo sequencing as a complementary approach to classic database searching. All
      evaluations were performed on a human intestinal metaproteome dataset. Pyrococcus
      furiosus proteome data were used to contrast database searching of metaproteomic
      data to a classic proteomic experiment. Searching against subsets of metaproteome
      databases and the use of multiple search engines increased the number of
      identifications. The integration of P. furiosus sequences in a metaproteomic
      sequence database showcased the limitation of the target-decoy-controlled false
      discovery rate approach in combination with large sequence databases. The
      selection of varying search engine parameters and the application of de novo
      sequencing represented useful methods to increase the reliability of the results.
      Based on our findings, we provide recommendations for the data analysis that help
      researchers to establish or improve analysis workflows in metaproteomics. 

PMID- 25778832
TI  - The Modified Glasgow Prognostic Score and Survival in Colorectal Cancer: A Pooled
      Analysis of the Literature.
AB  - BACKGROUND: It has been reported that the combination of inflammation parameters,
      such as albumin and C-reactive protein, in the modified Glasgow prognostic score
      (m-GPS) is a poor prognostic indicator in several malignancies. Here, we quantify
      the prognostic impact of this score and assess its value in colorectal cancer.
      METHODS: A systematic review of electronic databases was conducted to identify
      publications exploring the association of m-GPS with outcome in colorectal
      cancer. Overall survival (OS) was the primary outcome, and cancer-specific
      survival (CSS), progression-free survival, and disease-free survival were
      secondary outcomes. Data from studies reporting a hazard ratio (HR) and 95%
      confidence interval (CI) were included in a metaanalysis. Pooled HRs were
      computed and weighted using generic inverse-variance and random effects modeling.
      All statistical tests were two-sided. RESULTS: Nine studies, which included a
      total of 2,227 patients, were included in the analysis. Overall, according to
      multivariate analysis, m-GPS>=1 was independently associated with an HR for OS of
      1.69 (95% CI=1.4-2.04; P<0.00001), an effect observed in all stages of disease.
      Six studies including a total of 1,751 patients reported HR for CSS. Overall, a
      high m-GPS was associated with an HR for CSS of 1.84 (95% CI=1.43-2.37;
      P<0.00001). CONCLUSIONS: A high m-GPS is associated with poor OS in colorectal
      cancer. The m-GPS is a cheap and easily evaluable biomarker, and its
      incorporation into known prognostic scores for clinical decision making warrants
      further investigation in this setting.

PMID- 25778833
TI  - Consistency in compensatory eating responses following acute exercise in
      inactive, overweight and obese women.
AB  - It is often assumed that some individuals reliably increase energy intake (EI)
      post-exercise ('compensators') and some do not ('non-compensators'), leading
      researchers to examine the characteristics that distinguish these two groups.
      However, it is unclear whether EI post-exercise is stable over time. The present
      study examined whether compensatory eating responses to a single exercise bout
      are consistent within individuals across three pairs of trials. Physically
      inactive, overweight/obese women (n 28, BMI 30.3 (SD 2.9) kg/m2) participated in
      three pairs of testing sessions, with each pair consisting of an exercise (30 min
      of moderate-intensity walking) and resting testing day. EI was measured using a
      buffet meal 1 h post-exercise/rest. For each pair, the difference in EI (EIdiff =
      EIex - EIrest) was calculated, where EIex is the EI of the exercise session and
      EIrest is the EI of the resting session, and women were classified as a
      'compensator' (EIex > EIrest) or 'non-compensator' (EIex <= EIrest). The average
      EI on exercise days (3328.0 (SD 1686.2) kJ) was similar to those on resting days
      (3269.4 (SD 1582.4) kJ) (P= 0.67). Although EI was reliable within individuals
      across the three resting days (intraclass correlation coefficient (ICC) 0.75, 95
      % CI 0.60, 0.87; P< 0.001) and three exercise days (ICC 0.83, 95 % CI 0.70, 0.91;
      P< 0.001), the ICC for EIdiff across the three pairs of trials was low (ICC 0.20,
      95 % CI -0.02, 0.45; P= 0.04), suggesting that compensatory eating post-exercise
      is not a stable construct. Moreover, the classification of 'compensators'/'non
      compensators' was not reliable (kappa = -0.048; P= 0.66). The results were
      unaltered when 'relative' EI was used, which considers the energy expenditure of
      the exercise/resting sessions. Acute compensatory EI following an exercise bout
      is not reliable in overweight women. Seeking to understand what distinguishes
      'compensators' from 'non-compensators' based on a single eating episode post
      exercise is not justified.

PMID- 25778834
TI  - Neurobehavioral Deficits in a Rat Model of Recurrent Neonatal Seizures Are
      Prevented by a Ketogenic Diet and Correlate with Hippocampal Zinc/Lipid
      Transporter Signals.
AB  - The ketogenic diet (KD) has been shown to be effective as an antiepileptic
      therapy in adults, but it has not been extensively tested for its efficacy in
      neonatal seizure-induced brain damage. We have previously shown altered
      expression of zinc/lipid metabolism-related genes in hippocampus following
      penicillin-induced developmental model of epilepsy. In this study, we further
      investigated the effect of KD on the neurobehavioral and cognitive deficits, as
      well as if KD has any influence in the activity of zinc/lipid transporters such
      as zinc transporter 3 (ZnT-3), MT-3, ApoE, ApoJ (clusterin), and ACAT-1
      activities in neonatal rats submitted to flurothyl-induced recurrent seizures.
      Postnatal day 9 (P9), 48 Sprague-Dawley rats were randomly assigned to two
      groups: flurothyl-induced recurrent seizure group (EXP) and control group (CONT).
      On P28, they were further randomly divided into the seizure group without
      ketogenic diet (EXP1), seizure plus ketogenic diet (EXP2), the control group
      without ketogenic diet (CONT1), and the control plus ketogenic diet (CONT2).
      Neurological behavioral parameters of brain damage (plane righting reflex, cliff
      avoidance reflex, and open field test) were observed from P35 to P49. Morris
      water maze test was performed during P51-P57. Then hippocampal mossy fiber
      sprouting and the protein levels of ZnT3, MT3, ApoE, CLU, and ACAT-1 were
      detected by Timm staining and Western blot analysis, respectively. Flurothyl
      induced neurobehavioral toxicology and aberrant mossy fiber sprouting were
      blocked by KD. In parallel with these behavioral changes, rats treated with KD
      (EXP2) showed a significant down-regulated expression of ZnT-3, MT-3, ApoE,
      clusterin, and ACAT-1 in hippocampus when compared with the non-KD-treated EXP1
      group. Our findings provide support for zinc/lipid transporter signals being
      potential targets for the treatment of neonatal seizure-induced brain damage by
      KD. 

PMID- 25778835
TI  - Potential Health Risk of Herbal Distillates and Decoctions Consumption in Shiraz,
      Iran.
AB  - Concentration of 26 elements in 16 different herbal distillates and 5 herbal
      decoctions, were determined using inductively coupled plasma-mass spectrometry
      (ICP-MS). The elemental content of five raw herbal materials used for making
      decoctions and seven distilled and boiled residues were also evaluated by
      inductively coupled plasma optical emission spectrometry (ICP-OES). The results
      indicated that herbal products display a wide range of elemental concentrations.
      Compared with world health regulations, the concentrations of the elements in
      herbal distillates and decoctions did not exceed the recommended limits. The
      analysis of herbal extracts did not show a significant transfer of toxic elements
      during decoction preparation. Comparison of elemental content among fresh herbal
      material and herbal distillate and decoction of the same herb showed that,
      besides the elemental abundance of herbal organs, the ionic potential of elements
      also play an important role in elemental content of herbal products. Based on the
      results of the research, it seems that most health benefits attributed to herbal
      products (especially herbal distillates) are more related to their organic
      compounds rather than elemental composition. Calculated hazard quotient (HQ) and
      hazard index (HI) were used to evaluate the noncarcinogenic health risk from
      individual and combined metals via daily consumption of 100 ml of herbal
      distillates and 250 ml of herbal decoctions. Both HQs and HI through consumption
      of herbal distillates and herbal decoctions (except Valerian) were below 1.
      Apparently, daily consumption of herbal distillates and decoctions at the
      indicated doses poses no significant health risk to a normal adult.

PMID- 25778836
TI  - The Effect of Cerium Oxide Nanoparticle Valence State on Reactive Oxygen Species
      and Toxicity.
AB  - Cerium oxide (CeO2) nanoparticles, which are used in a variety of products
      including solar cells, gas sensors, and catalysts, are expected to increase in
      industrial use. This will subsequently lead to additional occupational exposures,
      making toxicology screenings crucial. Previous toxicology studies have presented
      conflicting results as to the extent of CeO2 toxicity, which is hypothesized to
      be due to the ability of Ce to exist in both a +3 and +4 valence state. Thus, to
      study whether valence state and oxygen vacancy concentration are important in
      CeO2 toxicity, CeO2 nanoparticles were doped with gadolinium to adjust the cation
      (Ce, Gd) and anion (O) defect states. The hypothesis that doping would increase
      toxicity and decrease antioxidant abilities as a result of increased oxygen
      vacancies and inhibition of +3 to +4 transition was tested. Differences in
      toxicity and reactivity based on valence state were determined in RLE-6TN rat
      alveolar epithelial and NR8383 rat alveolar macrophage cells using enhanced dark
      field microscopy, electron paramagnetic resonance (EPR), and annexin V/propidium
      iodide cell viability stain. Results from EPR indicated that as doping increased,
      antioxidant potential decreased. Alternatively, doping had no effect on toxicity
      at 24 h. The present results imply that as doping increases, thus subsequently
      increasing the Ce(3+)/Ce(4+) ratio, antioxidant potential decreases, suggesting
      that differences in reactivity of CeO2 are due to the ability of Ce to transition
      between the two valence states and the presence of increased oxygen vacancies,
      rather than dependent on a specific valence state. 

PMID- 25778837
TI  - Examining the Relationship Between Parental Anxiety and Treatment Response in
      Children and Adolescents with Autism Spectrum Disorder and Anxiety.
AB  - In response to the high co-occurrence of anxiety symptoms in youth with autism
      spectrum disorder (ASD), several interventions have been developed for this
      population. In spite of promising findings, some youth with ASD respond only
      minimally to such interventions. To understand potential factors that may impact
      treatment response, the current study explores the role of parental anxiety in
      youth treatment outcome. Thirty-one youth with ASD, ages 7-18, and their parents
      participated in the study. Parents completed the State/Trait Anxiety Inventory
      pre- and post-treatment. Contrary to previous research, there was no correlation
      between parental anxiety and youth anxiety at baseline or post-treatment.
      However, parental trait anxiety significantly decreased from pre- to post
      treatment for parents of treatment responders. The findings are consistent with
      previous research and suggest a youth-to-parent influence. 

PMID- 25778838
TI  - A Review of Level 2 Parent-Report Instruments Used to Screen Children Aged 1.5-5
      for Autism: A Meta-Analytic Update.
AB  - The present study utilized meta-analytic procedures to estimate the diagnostic
      validity of instruments used to screen young children, ages 1.5-5 years, for
      autism. Five scales met inclusion criteria, and data from 18 studies contributed
      the meta-analysis. Results revealed that 4 of 5 scales met criteria for "good"
      validity, including two broad band scales (instruments not restricted to
      screening for autism). The current results suggest that validity differences
      might be a function of how instruments sample across the DSM content domains.
      Specifically, high validity instruments included a higher proportion of items
      assessing social interaction skills. The availability of valid broad- and narrow
      band instruments, as well as implications for constructing future screening
      instruments, is discussed.

PMID- 25778839
TI  - Structural and functional characterization of two-domain laccase from
      Streptomyces viridochromogenes.
AB  - Laccase (EC 1.10.3.2) is one of the most common copper-containing oxidases found
      in many organisms and catalyses oxidation of primarily phenolic compounds by
      oxygen. A recently found bacterial laccase whose molecule is formed by two
      domains - the so called two-domain laccase (2DLac) or small laccase - has unusual
      resistance to inhibitors and an alkaline optimum of activity. The causes of these
      properties, as well as the biological function of two-domain laccases, are poorly
      understood. We performed an enzymatic and structural characterization of 2DLac
      from Streptomyces viridochromogenes (SvSL). It was cloned and overproduced in
      Escherichia coli. Phenolic compounds were oxidized in the presence of the enzyme
      under alkaline but not acidic conditions. Conversely, nonphenolic compounds were
      oxidized at acidic but not alkaline pH. SvSL catalysed oxidation of nonphenolic
      compounds more efficiently than that of phenols. Moreover, this two-domain
      laccase displayed a cytochrome c oxidase activity and exhibited no ferroxidase
      activity. The enzyme was resistant to specific inhibitors of copper-containing
      oxidases, such as NaN3 and NaF. We succeeded in generating X-ray quality crystals
      and solved their structure to a resolution of 2.4 A. SvSL is a homotrimer in its
      native state. Comparison of its structure with that of a three-domain laccase
      revealed differences in the second coordination sphere of the T2/T3 centre and
      solvent channels. The role of these differences in the resistance of the enzyme
      to inhibitors and the activity at alkaline pH is under discussion. 

PMID- 25778841
TI  - [Management of direct oral anticoagulants for invasive procedures].
AB  - Three new Direct Oral Anticoagulants (DOACs), rivaroxaban, apixaban and
      dabigatran etexilate are available on the French market. Management of DOAC
      induced bleeding risk remains challenging. For elective procedures with high
      hemorrhagic risk, a last DOAC intake five days before procedure ensures complete
      elimination in all patients. Heparin bridging therapy should be proposed only to
      patients at high thrombotic risk. For elective procedures with low hemorrhagic
      risk, the DOAC intake of the night before procedure should be omitted. For urgent
      procedures with high bleeding risk, DOAC plasmatic concentration can be helpful:
      concentration lower than 30 ng/mL should enable performing the procedure; a high
      concentration is associated with a higher bleeding risk, especially if higher
      than 400 ng/mL. In case of massive bleeding, no antidote is approved yet;
      activated prothrombin concentrates or non-activated 4-factors prothrombin
      concentrates could be considered.

PMID- 25778842
TI  - [Successful management of an acquired uterine arteriovenous malformation by
      selective ligation of the internal iliac artery].
AB  - Uterine arteriovenous malformations can be congenital or acquired. When acquired,
      they result from abnormal arteriovenous communication between one or more uterine
      arteries and a myometrial and/or endometrial venous plexus, without the
      interposition of a vascular nidus. Arteriovenous malformations are composed of a
      tortuous net of fragile low-resistant arteriovenous shunts. Uterine arteriovenous
      malformations create a rare and potentially life-threatening condition. The
      method of treatment is determined by symptoms, desire for future fertility,
      extent, and location of the malformation. The first treatment option for uterine
      arteriovenous malformation is hysterectomy, and the second option is uterine
      artery embolization. Selective ligation of the vessels supplying the malformation
      is an effective treatment option when conservative methods have failed. The
      present report describes a patient whose uterine arteriovenous malformation was
      successfully managed by selective ligation of the internal iliac artery. 

PMID- 25778840
TI  - Inhibitor of differentiation 4 (ID4) acts as an inhibitor of ID-1, -2 and -3 and
      promotes basic helix loop helix (bHLH) E47 DNA binding and transcriptional
      activity.
AB  - The four known ID proteins (ID1-4, Inhibitor of Differentiation) share a
      homologous helix loop helix (HLH) domain and act as dominant negative regulators
      of basic-HLH transcription factors. ID proteins also interact with many non-bHLH
      proteins in complex networks. The expression of ID proteins is increasingly
      observed in many cancers. Whereas ID-1, ID-2 and ID-3, are generally considered
      as tumor promoters, ID4 on the contrary has emerged as a tumor suppressor. In
      this study we demonstrate that ID4 heterodimerizes with ID-1, -2 and -3 and
      promote bHLH DNA binding, essentially acting as an inhibitor of inhibitors of
      differentiation proteins. Interaction of ID4 was observed with ID1, ID2 and ID3
      that was dependent on intact HLH domain of ID4. Interaction with bHLH protein E47
      required almost 3 fold higher concentration of ID4 as compared to ID1.
      Furthermore, inhibition of E47 DNA binding by ID1 was restored by ID4 in an EMSA
      binding assay. ID4 and ID1 were also colocalized in prostate cancer cell line
      LNCaP. The alpha helix forming alanine stretch N-terminal, unique to HLH ID4
      domain was required for optimum interaction. Ectopic expression of ID4 in DU145
      prostate cancer line promoted E47 dependent expression of CDKNI p21. Thus
      counteracting the biological activities of ID-1, -2 and -3 by forming inactive
      heterodimers appears to be a novel mechanism of action of ID4. These results
      could have far reaching consequences in developing strategies to target ID
      proteins for cancer therapy and understanding biologically relevant ID
      interactions. 

PMID- 25778843
TI  - Combination of IL-24 and cisplatin inhibits angiogenesis and lymphangiogenesis of
      cervical cancer xenografts in a nude mouse model by inhibiting VEGF, VEGF-C and
      PDGF-B.
AB  - The aim of the present study was to investigate the synergistic inhibitory
      effects of recombinant IL-24 delivered by pDC316-hIL-24 transfection and
      cisplatin (DDP) on angiogenesis and lymphangiogenesis in a cervical cancer
      xenograft model established in nude mice. Thirty-six mice (successful model) were
      randomly divided into six groups (n=6 in each): i) phosphate-buffered saline
      control; ii) empty plasmid; iii) half-dose DDP; iv) recombinant interleukin (IL)
      24; v) full-dose DDP; and vi) combined treatment. Tumor growth and animal weight
      were measured every 3 days. Animals were sacrificed by cervical dislocation at 2
      weeks after the cessation of treatment. Tumor inhibition was compared after
      intervention. Lymph node metastasis was evaluated by immunohistochemical (IHC)
      analysis of vascular endothelial growth factor (VEGF), VEGF-C and VEGFR-3.
      Platelet-derived growth factor (PDGF)-B expression was also investigated by
      western blot analysis. Microvessel density was evaluated by IHC analysis of CD34
      expression. The tumor growth was slower or reduced in the IL-24 and half-dose
      DDP+IL-24 groups. The expression of VEGF and microvessel density in the IL-24
      group was significantly lower than that in the other groups. VEGF (VEGF-A), VEGF
      C, VEGFR-3 and PDGF-B expression was significantly decreased in the IL-24 and
      half-dose DDP+IL-24 groups compared with that in the other groups (P<0.001). The
      recombinant plasmid pDC316-hIL-24 acts synergistically with cisplatin to inhibit
      tumor growth and angiogenesis. Our data indicate that these effects are mediated
      by downregulation of VEGF, VEGF-C and PDGF-B expression. Thus, IL-24 may enhance
      tumor chemosensitivity to cisplatin, which may be an important strategy for
      reducing the side-effects of this chemotherapy. 

PMID- 25778844
TI  - The incidence of SCN1A-related Dravet syndrome in Denmark is 1:22,000: a
      population-based study from 2004 to 2009.
AB  - Dravet syndrome is a severe infantile-onset epileptic encephalopathy associated
      with mutations in the sodium channel alpha-1 subunit gene SCN1A. We aimed to
      describe the incidence of Dravet syndrome in the Danish population. Based on a 6
      year birth cohort from 2004 to 2009, we propose an incidence of 1:22,000, which
      is higher than what has been established earlier. We identified 17 cases with
      SCN1A mutation-positive Dravet syndrome. Fifteen patients were found, by
      conventional Sanger sequencing. Two additional patients with clinical Dravet
      syndrome, but without a detectable SCN1A mutation by Sanger sequencing, were
      diagnosed with a SCN1A mutation after using a targeted next-generation sequencing
      gene panel. 

PMID- 25778845
TI  - The role of antiparasite treatment experiments in assessing the impact of
      parasites on wildlife.
AB  - It has become increasingly clear that parasites can have significant impacts on
      the dynamics of wildlife populations. Recently, researchers have shifted from
      using observational approaches to infer the impact of parasites on the health and
      fitness of individuals to using antiparasite drug treatments to test directly the
      consequences of infection. However, it is not clear the extent to which these
      experiments work in wildlife systems, or whether the results of these individual
      level treatment experiments can predict the population-level consequences of
      parasitism. Here, we assess the results of treatment experiments, laying out the
      benefits and limitations of this approach, and discuss how they can be used to
      improve our understanding of the role of parasites in wildlife populations. 

PMID- 25778847
TI  - Erratum: correction to: aclidinium bromide plus formoterol for the treatment of
      chronic obstructive pulmonary disease.

PMID- 25778848
TI  - New insights into the mechanisms of gene electrotransfer--experimental and
      theoretical analysis.
AB  - Gene electrotransfer is a promising non-viral method of gene delivery. In our in
      vitro study we addressed open questions about this multistep process: how
      electropermeabilization is related to electrotransfer efficiency; the role of DNA
      electrophoresis for contact and transfer across the membrane; visualization and
      theoretical analysis of DNA-membrane interaction and its relation to final
      transfection efficiency; and the differences between plated and suspended cells.
      Combinations of high-voltage and low-voltage pulses were used. We obtained that
      electrophoresis is required for the insertion of DNA into the permeabilized
      membrane. The inserted DNA is slowly transferred into the cytosol, and nuclear
      entry is a limiting factor for optimal transfection. The quantification and
      theoretical analysis of the crucial parameters reveals that DNA-membrane
      interaction (NDNA) increases with higher DNA concentration or with the addition
      of electrophoretic LV pulses while transfection efficiency reaches saturation. We
      explain the differences between the transfection of cell suspensions and plated
      cells due to the more homogeneous size, shape and movement of suspended cells.
      Our results suggest that DNA is either translocated through the stable
      electropores or enters by electo-stimulated endocytosis, possibly dependent on
      pulse parameters. Understanding of the mechanisms enables the selection of
      optimal electric protocols for specific applications. 

PMID- 25778849
TI  - 5alpha-Reductase inhibitors increase acute coronary syndrome risk in patients
      with benign prostate hyperplasia.
AB  - BACKGROUND: This study explored the possible association between the use of two
      typical 5ARIs (finasteride and dutasteride) and the risk of acute coronary
      syndrome (ACS) in patients with benign prostate hyperplasia (BPH). METHODS: From
      the claims data of the Taiwan National Health Insurance (NHI) Taiwan, we
      identified 1843 ACS cases among BPH patients and randomly selected 7330 controls
      without ACS, with a similar mean age of 73 years. Multivariate logistic
      regression analysis estimated the odds ratio (OR) and 95 % confidence interval
      (CI) for the relationship between the 5ARIs medications and ACS risk. RESULTS: We
      found that BPH patients who had received treatment with both finasteride and
      dutasteride were at a higher risk of ACS with an OR of 3.47 (95 % CI 1.05-11.5),
      compared to patients without 5ARIs treatment. Furthermore, the dosage analysis
      showed that there were no significant associations between ACS risk and uses of a
      single drug medication regardless the dosages. The ORs for those who took only
      dutasteride were 1.07 (95 % CI 0.39-2.99) with low dose and 0.73 (95 % CI 0.38
      1.44) with high dose. The ORs for those who took only finasteride were 1.30 (95 %
      CI 0.89-1.92) with low dose and 0.98 (95 % CI 0.19-5.13) with high dose.
      CONCLUSION: This population-based nested case-control study suggests that 5ARI
      use may increase ACS risk among patients with BPH when patients were exposed to
      both finasteride and dutasteride.

PMID- 25778850
TI  - Rosuvastatin-Induced Carotid Plaque Regression in Patients With Inflammatory
      Joint Diseases: The Rosuvastatin in Rheumatoid Arthritis, Ankylosing Spondylitis
      and Other Inflammatory Joint Diseases Study.
AB  - OBJECTIVE: Patients with rheumatoid arthritis (RA) and carotid artery plaques
      have an increased risk of acute coronary syndromes. Statin treatment with the
      goal of achieving a low-density lipoprotein (LDL) cholesterol level of <=1.8
      mmoles/liter (<=70 mg/dl) is recommended for individuals in the general
      population who have carotid plaques. The aim of the ROsuvastatin in Rheumatoid
      Arthritis, Ankylosing Spondylitis and other inflammatory joint diseases (RORA-AS)
      study was to evaluate the effect of 18 months of intensive lipid-lowering
      treatment with rosuvastatin with regard to change in carotid plaque height.
      METHODS: Eighty-six patients (60.5% of whom were female) with carotid plaques and
      inflammatory joint disease (55 with RA, 21 with AS, and 10 with psoriatic
      arthritis) were treated with rosuvastatin to obtain the LDL cholesterol goal.
      Carotid plaque height was evaluated by B-mode ultrasonography. RESULTS: The mean
      +/- SD age of the patients was 60.8 +/- 8.5 years, and the median compliance with
      rosuvastatin treatment was 97.9% (interquartile range [IQR] 96.0-99.4). At
      baseline, the median number and height of the carotid plaques were 1.0 (range 1
      8) and 1.80 mm (IQR 1.60-2.10), respectively. The mean +/- SD change in carotid
      plaque height after 18 months of treatment with rosuvastatin was -0.19 +/- 0.35
      mm (P < 0.0001). The mean +/- SD baseline LDL cholesterol level was 4.0 +/- 0.9
      mmoles/liter (154.7 +/- 34.8 mg/dl), and the mean reduction in the LDL
      cholesterol level was -2.3 mmoles/liter (95% confidence interval [95% CI] -2.48, 
      2.15) (-88.9 mg/dl [95% CI -95.9, -83.1]). The mean +/- SD LDL cholesterol level
      during the 18 months of rosuvastatin treatment was 1.7 +/- 0.4 mmoles/liter (area
      under the curve). After adjustment for age/sex/blood pressure, no linear
      relationship between a reduction in carotid plaque height and the level of LDL
      cholesterol exposure during the study period was observed. Attainment of the LDL
      cholesterol goal of <=1.8 mmoles/liter (<=70 mg/dl) or the amount of change in
      the LDL cholesterol level during the study period did not influence the degree of
      carotid plaque height reduction. CONCLUSION: Intensive lipid-lowering treatment
      with rosuvastatin induced atherosclerotic regression and reduced the LDL
      cholesterol level significantly in patients with inflammatory joint disease.

PMID- 25778851
TI  - Longitudinal development of number line estimation and mathematics performance in
      primary school children.
AB  - Children's ability to relate number to a continuous quantity abstraction
      visualized as a number line is widely accepted to be predictive of mathematics
      achievement. However, a debate has emerged with respect to how children's
      placements are distributed on this number line across development. In the current
      study, different models were applied to children's longitudinal number placement
      data to get more insight into the development of number line representations in
      kindergarten and early primary school years. In addition, longitudinal
      developmental relations between number line placements and mathematical
      achievement, measured with a national test of mathematics, were investigated
      using cross-lagged panel modeling. A group of 442 children participated in a 3
      year longitudinal study (ages 5-8 years) in which they completed a number-to
      position task every 6 months. Individual number line placements were fitted to
      various models, of which a one-anchor power model provided the best fit for many
      of the placements at a younger age (5 or 6 years) and a two-anchor power model
      provided better fit for many of the children at an older age (7 or 8 years). The
      number of children who made linear placements also grew with age. Cross-lagged
      panel analyses indicated that the best fit was provided with a model in which
      number line acuity and mathematics performance were mutually predictive of each
      other rather than models in which one ability predicted the other in a non
      reciprocal way. This indicates that number line acuity should not be seen as a
      predictor of math but that both skills influence each other during the
      developmental process.

PMID- 25778852
TI  - [Hyperviscosity syndrome].
AB  - Hyperviscosity syndrome is a life-threatening complication. Clinical
      manifestations include neurological impairment, visual disturbance and bleeding.
      Measurement of plasma or serum viscosity by a viscometer assesses the diagnosis.
      Funduscopic examination is a key exam because abnormalities are well-correlated
      with abnormal plasma viscosity. Etiologies are various but symptomatic
      hyperviscosity is more common in Waldenstrom's macroglobulinemia and multiple
      myeloma. Prompt treatment is needed: treatment of the underlying disease should
      be considered, but generally not sufficient. Symptomatic measures aim to not
      exacerbate blood viscosity while urgent plasmapheresis effectively reduces the
      paraprotein concentration and relieves symptoms. 

PMID- 25778853
TI  - [End stage renal disease and ventricular arrhythmia. Hemodialysis and
      hemodiafiltration differently affect ventricular repolarization].
AB  - Various factors (hypertension [27%], diabetes mellitus [40%]) and their
      cardiovascular complications play an important role in the genesis of end stage
      renal disease. Furthermore, primary kidney diseases (glomerulonephritis,
      tubulointerstitial nephritis, obstructive uropathy, analgesic nephropathy,
      polycystic kidney disease, autoimmune diseases) have an unfavorable effect on the
      cardiovascular outcome of this particular population. Increased susceptibility
      for arrhythmias may be caused by intermittent volume overload, metabolic
      disturbance, renal anemia, structural and electrophysiological changes of the
      myocardium, inflammatory mechanisms that may worsen the mortality statistics of
      these patients. A novel renal replacement method, hemodiafiltration - based on a
      convective transport - ensures reduced mortality that may be attributed to a
      decreased occurrence of arrhythmias. The aim of this paper is to review the
      pathogenetic factors taking part in the arrhythmogenesis of end stage renal
      disease and to provide diagnostic and therapeutic opportunities that can help in
      the prediction and prevention of arrhythmias.

PMID- 25778854
TI  - [Critical issues of the biopsychosocial treatment of Parkinson's disease].
AB  - This paper is a summary report on the basic questions of the biopsychosocial
      approach to Parkinson's disease. It deals with cognitive, affective and
      psychological health issues which significantly influence the outcome of the
      physical rehabilitation. In spite of the unchanged cognitive status, the
      psychological burden of the changes in the quality of life, the obstruction, the
      change in the affective tone, and the shrinking ability to fulfil social roles
      decrease the patient's quality of life. An interdisciplinary approach is best
      suited for mitigating these effects. Not only the patient but also his/her family
      and environment is seriously affected by the disease and its consequences.
      Treatment and rehabilitation options for increasing or maintaining the quality of
      life of the affected patients are diverse, and significantly depend on the
      features of the health care system. The authors believe that the following review
      emphasizing health psychological principles may contribute to the work of
      professionals working in clinical and rehabilitational fields and through them
      may increase the quality of life of patients and their family.

PMID- 25778855
TI  - [Comparative dissolution test of modified release pharmaceutical products for
      potassium replacement].
AB  - INTRODUCTION: Oral potassium replacement is still inevitable. To reduce the
      irritation of the gastric and intestinal mucosa, pellet and matrix based
      formulations ensuring extended release of potassium chloride are used. The
      dissolution tests may help to understand the in vivo steps of the release of
      potassium chloride and the absorption of potassium. AIM: Using dissolution tests
      extended to 12 hours the authors evaluated potassium chloride release
      characteristics of pellet and matrix tablet based formulations used for potassium
      replacement. METHOD: The tests were performed in line with the
      CPMP/EWP/QWP/1401/98 guideline at nine time points (0, 1, 2, 3, 4, 5, 7, 9 and 12
      hours) in three dissolution media (0.1 M hydrochloric acid, pH 1.2; acetate
      buffer, pH 4.5; phosphate buffer, pH 6.8). RESULTS: Similar results were found in
      all three dissolution media. CONCLUSIONS: It is conceivable, that the release of
      potassium chloride begins already in the stomach (pH = 1.2) and at an average
      speed of gastrointestinal transit - in about 6-7 hours - 80% of the potassium
      chloride content of both formulations is dissolved by the time of the entrance to
      the large bowel. It seems likely, that in vivo in the proximal section of the
      gastrointestinal tract more potassium chloride is dissolved out of the matrix
      based formulation, than from the pellet based one. Both formulations meet the
      clinical requirements of the effective potassium chloride release.

PMID- 25778856
TI  - [Relationships between psychological well-being, lifestyle factors and
      fertility].
AB  - INTRODUCTION: 10 to 15% of the Hungarian fertile age population struggles with
      reproductivity problems. Previous researches have shown that psychological well
      being and lifestyle factors play a pivotal role in overall health status, which
      is closely related to fertility. AIM: The aim of the study was to examine
      fertility-related psychological and lifestyle factors in a Hungarian sample.
      METHOD: 194 women (115 infertile and 79 fertile) took part in the study.
      Standardized, validated questionnaires were used for the assessment of
      psychological factors and self-administered questions were used for exploring
      lifestyle factors. RESULTS: The results show that infertile women are younger
      (33.98+/-4.89 vs. 36.43+/-5.81 years, p<0.005) and their psychological status is
      significantly worse compared to their fertile counterparts. The number of their
      depressive (BDI 14.00+/-12.21 vs. 7.79+/-9.17, p<0.005) and anxiety symptoms is
      higher (STAI-T 48.53+/-10.56 vs. 40.25+/-10.65, p<0.005) compared to fertile
      women. Findings related to lifestyle factors show that lower level of fluid
      consumption (1.71+/-0.67 vs. 1.95+/-0.68, p<0.05) and diet (31.30% vs. 18.42%,
      p<0.05) is significantly related to infertility. In this sample higher level of
      fluid consumption was associated with the fertile group (OR = 1.65, CI = 2.58
      1.06), independently of body mass index and age. CONCLUSIONS: The results confirm
      the findings of international researches showing that women struggling with
      infertility are in worse psychological condition than their fertile counterparts.
      The authors conclude that the findings demand further investigations and follow
      up studies in order to more specifically determine the relationship between fluid
      consumption and fertility.

PMID- 25778857
TI  - [Functional neurocognitive disorders: pathogenetic role, diagnosis and
      therapeutic guidelines].

PMID- 25778858
TI  - Building interventions in primary health care for long-term effectiveness in
      health promotion and disease prevention. A focus on complex and multi-risk
      interventions.

PMID- 25778859
TI  - Hypothalamic neurones governing glucose homeostasis.
AB  - The notion that the brain directly controls the level of glucose in the blood
      (glycaemia) independent of its known action on food intake and body weight has
      been known ever since 1849. That year, the French physiologist Dr Claude Bernard
      reported that physical puncture of the floor of the fourth cerebral ventricle
      rapidly leads to an increased level of sugar in the blood (and urine) in rabbits.
      Despite this important discovery, it took approximately 150 years before
      significant efforts aimed at understanding the underlying mechanism of brain
      mediated control of glucose metabolism were made. Technological developments
      allowing for genetically-mediated manipulation of selected molecular pathways in
      a neurone-type-specific fashion unravelled the importance of specific molecules
      in specific neuronal populations. These neuronal pathways govern glucose
      metabolism in the presence and even in the absence of insulin. Also, a
      peculiarity of these pathways is that certain biochemically-defined neurones
      govern glucose metabolism in a tissue-specific fashion.

PMID- 25778860
TI  - Acceptability, feasibility and challenges of implementing an HIV prevention
      intervention for people living with HIV/AIDS among healthcare providers in
      Mozambique: results of a qualitative study.
AB  - Despite the Mozambique government's efforts to curb human immunodeficiency virus
      (HIV)/acquired immune deficiency syndrome (AIDS), national prevalence is 11.5%
      and support is needed to expand HIV-related services and improve program quality.
      Positive prevention (PP) programs, which prioritize HIV prevention with people
      living with HIV and AIDS (PLHIV), have been recognized as an important
      intervention for preventing new HIV infections. To address this, an evidence
      based PP training intervention was implemented with HIV healthcare providers in
      Mozambique. This study focuses on the acceptability and feasibility of a PP
      intervention in HIV clinics from the healthcare provider perspective. In-depth
      interviews were conducted with 31 healthcare providers from three provinces who
      participated in PP trainings in Mozambique. Interview data were coded using
      content analysis. Study data suggest that healthcare providers found PP
      acceptable, feasible to implement in their HIV work in clinic settings, and
      valued this strategy to improve HIV prevention. The PP training also led
      providers to feel more comfortable counseling their patients about prevention,
      with a more holistic approach that included HIV testing, treatment and
      encouraging PLHIV to live positively. While overall acceptance of the PP training
      was positive, several barriers to feasibility surfaced in the data. Patient-level
      barriers included resistance to disclosing HIV status due to fear of stigma and
      discrimination, difficulty negotiating for condom use, difficulty engaging men in
      testing and treatment, and the effects of poverty on accessing care. Providers
      also identified work environment barriers including high patient load, time
      constraints, and frequent staff turnover. Recognizing PP as an important
      intervention, healthcare providers should be trained to provide comprehensive
      prevention, care and treatment for PLHIV. Further work is needed to explore the
      complex social dynamics and cultural challenges such as gender inequalities,
      stigma and discrimination which hinder the full impact of PP interventions in
      this context. 

PMID- 25778861
TI  - D2 dopamine receptor regulation of learning, sleep and plasticity.
AB  - Dopamine and sleep have been independently linked with hippocampus-dependent
      learning. Since D2 dopaminergic transmission is required for the occurrence of
      rapid-eye-movement (REM) sleep, it is possible that dopamine affects learning by
      way of changes in post-acquisition REM sleep. To investigate this hypothesis, we
      first assessed whether D2 dopaminergic modulation in mice affects novel object
      preference, a hippocampus-dependent task. Animals trained in the dark period,
      when sleep is reduced, did not improve significantly in performance when tested
      24h after training. In contrast, animals trained in the sleep-rich light period
      showed significant learning after 24h. When injected with the D2 inverse agonist
      haloperidol immediately after the exploration of novel objects, animals trained
      in the light period showed reduced novelty preference upon retesting 24h later.
      Next we investigated whether haloperidol affected the protein levels of
      plasticity factors shown to be up-regulated in an experience-dependent manner
      during REM sleep. Haloperidol decreased post-exploration hippocampal protein
      levels at 3h, 6h and 12h for phosphorylated Ca(2+)/calmodulin-dependent protein
      kinase II, at 6h for Zif-268; and at 12h for the brain-derived neurotrophic
      factor. Electrophysiological and kinematic recordings showed a significant
      decrease in the amount of REM sleep following haloperidol injection, while slow
      wave sleep remained unaltered. Importantly, REM sleep decrease across animals was
      strongly correlated with deficits in novelty preference (Rho=0.56, p=0.012).
      Altogether, the results suggest that the dopaminergic regulation of REM sleep
      affects learning by modulating post-training levels of calcium-dependent
      plasticity factors. 

PMID- 25778862
TI  - Association of P2RY12 polymorphisms with eosinophil and platelet activation in
      patients with aspirin-exacerbated respiratory disease.

PMID- 25778863
TI  - Resolution of alcohol-induced respiratory symptoms following aspirin
      desensitization in aspirin-exacerbated respiratory disease.

PMID- 25778864
TI  - Active site labeling of cysteine cathepsins by a straightforward
      diazomethylketone probe derived from the N-terminus of human cystatin C.
AB  - We designed a straightforward biotinylated probe using the N-terminal substrate
      like region of the inhibitory site of human cystatin C as a scaffold, linked to
      the thiol-specific reagent diazomethylketone group as a covalent warhead (i.e.
      Biot-(PEG)2-Ahx-LeuValGly-DMK). The irreversible activity-based probe bound
      readily to cysteine cathepsins B, L, S and K. Moreover affinity labeling is
      sensitive since active cathepsins were detected in the nM range using an
      ExtrAvidin-peroxidase conjugate for disclosure. Biot-(PEG)2-Ahx-LeuValGly-DMK
      allowed a slightly more pronounced labeling for cathepsin S with a compelling
      second-order rate constant for association (kass = 2,320,000 M(-1) s(-1)).
      Labeling of the active site is dose-dependent as observed using 6-cyclohexylamine
      4-piperazinyl-1,3,5-triazine-2-carbonitrile, as competitive inhibitor of
      cathepsins. Finally we showed that Biot-(PEG)2-Ahx-LeuValGly-DMK may be a simple
      and convenient tool to label secreted and intracellular active cathepsins using a
      myelomonocytic cell line (THP-1 cells) as model.

PMID- 25778865
TI  - Suppression of DACH1 promotes migration and invasion of colorectal cancer via
      activating TGF-beta-mediated epithelial-mesenchymal transition.
AB  - DACH1 has been found down-regulated in a variety of human cancers, but its
      clinical significance and functional roles in colorectal cancer (CRC) remain
      unknown. In this study, we identified DACH1 as a tumor suppressor in CRC.
      Suppression of DACH1 strikingly increased cell growth, migration and invasion
      potential of CRC cell line SW480. Expression analysis of a set of epithelial
      mesenchymal transition (EMT) markers by RT-qPCR and western blot showed an
      increase in the expression of mesenchymal markers (vimentin and N-cadherin) and a
      reduction in the expression of epithelial marker (E-cadherin and gamma-catenin).
      Furthermore, EMT characteristics in DACH1-downregulated CRC cells were abrogated
      by TGF-beta inhibitor SB431542. DACH1 overexpression reduced TGF-beta-induced EMT
      and inhibited SW480 cell invasion which can be reversed in the presence of TGF
      beta. Thus, our results suggest that DACH1 loss of function results in increased
      cell growth, motility and invasiveness through TGF-beta-mediated EMT, and DACH1
      loss of function has important therapeutic implications for targeted therapies of
      CRC. 

PMID- 25778866
TI  - Graphene substrate for inducing neurite outgrowth.
AB  - A few recent studies demonstrated that graphene may have cytocompatibility with
      several cell types. However, when assessing cell behavior on graphene, there has
      been no precise control over the quality of graphene, number of graphene layers,
      and substrate surface coverage by graphene. In this study, using well-controlled
      monolayer graphene film substrates we tested the cytocompatibility of graphene
      for human neuroblastoma (SH-SY5Y) cell culture. A large-scale monolayer graphene
      film grown on Cu foils by chemical vapor deposition (CVD) could be successfully
      transferred onto glass substrates by wet transfer technique. We observed that
      graphene substrate could induce enhanced neurite outgrowth, both in neurite
      length and number, compared with control glass substrate. Interestingly, the
      positive stimulatory effect by graphene was achieved even in the absence of
      soluble neurogenic factor, retinoic acid (RA). Key genes relevant to cell
      neurogenesis, e.g., neurofilament light chain (NFL), were also upregulated on
      graphene. Inhibitor studies suggested that the graphene stimulation of cellular
      neurogenesis may be achieved through focal adhesion kinase (FAK) and p38 mitogen
      activated protein kinase (MAPK) cascades. Our data indicate that graphene may be
      exploited as a platform for neural regenerative medicine, and the suggested
      molecular mechanism may provide an insight into the graphene control of neural
      cells. 

PMID- 25778867
TI  - High expression of sphingosine kinase 1 is associated with poor prognosis in
      nasopharyngeal carcinoma.
AB  - It has been reported that sphingosine kinase 1 (SPHK1), an oncogenic enzyme, was
      involved in the development and progression of a number of human cancers.
      However, the role of SPHK1 in nasopharyngeal carcinoma (NPC) is largely unknown.
      The present study aimed to characterize the expression of SPHK1 in human NPC and
      evaluate its clinical significance. Real-time quantitative reverse transcriptase
      polymerase chain reaction (qRT-PCR) and Western blot analyses showed that the
      expression of SPHK1 mRNA and protein in NPC specimens was significantly higher
      than that in non-tumorous nasopharyngeal mucosa biopsies. Immunohistochemistry
      (IHC) was conducted to characterize the expression pattern of SPHK1 in 142
      archived paraffin-embedded NPC specimens. Statistical analyses revealed that high
      levels of SPHK1 expression were associated with the clinical stages, locoregional
      recurrence and distant metastasis of NPC. NPC patients with high levels of SPHK1
      expression had shorter survival time, whereas those with lower levels of SPHK1
      expression survived longer. Moreover, multivariate analysis suggested that SPHK1
      up-regulation was an independent prognostic factor for NPC. Our results suggest
      for the first time that SPHK1 is involved in the development and progression of
      NPC, which can be used as a useful prognostic marker for NPC patients and may be
      an effective target for treating NPC. 

PMID- 25778868
TI  - Novel odorant-binding proteins and their expression patterns in grasshopper,
      Oedaleus asiaticus.
AB  - Insects use olfaction to detect exogenous odors and adapt to environments. In
      their olfaction systems, odorant-binding proteins (OBPs) are believed to be a key
      component. The unique OBP system of each species reflects the evolution of
      chemosensation of insects with habits. Here, we for the first time identified 15
      OBPs, OasiOBP1-15, of a grasshopper, Oedaleus asiaticus, that lives in the
      grasslands of Northern China and is closely related to the locust, Locusta
      migratoria. OasiOBP9 and OasiOBP10 are specifically expressed in the antennae.
      Other OBPs are expressed in the antennae as well as other chemosensory organs,
      such as the mouthparts and wings. Significantly more OasiOBP7 was detected in
      male than female antennae, but there are 9 OBPs that were more expressed in
      female than male antennae by quantitative real-time PCR. Phylogenetic analysis
      indicated that most of the O. asiaticus OBPs are similar to those of L.
      migratoria, but some are substantially different. This indicates that the OBPs
      originally evolved in a common ancestor, but their unique chemosensory systems
      are adapted to different ecosystems. 

PMID- 25778869
TI  - Autophagy and gap junctional intercellular communication inhibition are involved
      in cadmium-induced apoptosis in rat liver cells.
AB  - Cadmium (Cd) is known to induce hepatotoxicity, yet the underlying mechanism of
      how this occurs is not fully understood. In this study, Cd-induced apoptosis was
      demonstrated in rat liver cells (BRL 3A) with apoptotic nuclear morphological
      changes and a decrease in cell index (CI) in a time- and concentration-dependent
      manner. The role of gap junctional intercellular communication (GJIC) and
      autophagy in Cd-induced apoptosis was investigated. Cd significantly induced GJIC
      inhibition as well as downregulation of connexin 43 (Cx43). The prototypical gap
      junction blocker carbenoxolone disodium (CBX) exacerbated the Cd-induced decrease
      in CI. Cd treatment was also found to cause autophagy, with an increase in mRNA
      expression of autophagy-related genes Atg-5, Atg-7, Beclin-1, and microtubule
      associated protein light chain 3 (LC3) conversion from cytosolic LC3-I to
      membrane-bound LC3-II. The autophagic inducer rapamycin (RAP) prevented the Cd
      induced CI decrease, while the autophagic inhibitor chloroquine (CQ) caused a
      further reduction in CI. In addition, CBX promoted Cd-induced autophagy, as well
      as changes in expression of Atg-5, Atg-7, Beclin-1 and LC3. CQ was found to block
      the Cd-induced decrease in Cx43 and GJIC inhibition, whereas RAP had opposite
      effect. These results demonstrate that autophagy plays a protective role during
      Cd-induced apoptosis in BRL 3A cells during 6 h of experiment, while autophagy
      exacerbates Cd-induced GJIC inhibition which has a negative effect on cellular
      fate. 

PMID- 25778870
TI  - Cysteine protease antigens cleave CD123, the alpha subunit of murine IL-3
      receptor, on basophils and suppress IL-3-mediated basophil expansion.
AB  - Th2 type immune responses are essential for protective immunity against parasites
      and play crucial roles in allergic disorders. Helminth parasites secrete a
      variety of proteases for their infectious cycles including for host entry, tissue
      migration, and suppression of host immune effector cell function. Furthermore, a
      number of pathogen-derived antigens, as well as allergens such as papain, belong
      to the family of cysteine proteases. Although the link between protease activity
      and Th2 type immunity is well documented, the mechanisms by which proteases
      regulate host immune responses are largely unknown. Here, we demonstrate that the
      cysteine proteases papain and bromelain selectively cleave the alpha subunit of
      the IL-3 receptor (IL-3Ralpha/CD123) on the surface of murine basophils. The
      decrease in CD123 expression on the cell surface, and the degradation of the
      extracellular domain of recombinant CD123 were dependent on the protease activity
      of papain and bromelain. Pre-treatment of murine basophils with papain resulted
      in inhibition of IL-3-IL-3R signaling and suppressed IL-3- but not thymic stromal
      lymphopoietin-induced expansion of basophils in vitro. Our unexpected findings
      illuminate a novel mechanism for the regulation of basophil functions by protease
      antigens. Because IL-3 plays pivotal roles in the activation and proliferation of
      basophils and in protective immunity against helminth parasites, pathogen-derived
      proteases might contribute to the pathogenesis of infections by regulating IL-3
      mediated functions in basophils.

PMID- 25778871
TI  - Fetomaternal hemorrhage (FMH), an update: review of literature and an
      illustrative case.
AB  - BACKGROUND: Blood trafficking from fetus to mother and vice versa is a well-known
      physiological event that occurs at any stage in pregnancy. If the fetus looses
      high blood quantities to the maternal blood stream it becomes symptomatic. These
      symptoms can vary from cardiovascular distress to fetal death. MATERIALS AND
      METHODS: We give a review of current literature on Fetomaternal hemorrhage (FMH).
      CONCLUSION: This article highlights the importance of physician's awareness on
      detecting this rare but life threatening entity with both severe consequences for
      mother and neonate. The traditional measurement of FMH and the co-usage of alpha
      fetoprotein are debated. To conclude we describe and discuss an illustrative case
      of FMH. This article gives an applicatory overview of symptoms, diagnostics and
      treatment of FMH to facilitate physicians to detect this disease precociously.

PMID- 25778872
TI  - A novel classification of frontal bone fractures: The prognostic significance of
      vertical fracture trajectory and skull base extension.
AB  - PURPOSE: The broad spectrum of frontal bone fractures, including those with
      orbital and skull base extension, is poorly understood. We propose a novel
      classification scheme for frontal bone fractures. METHODS: Maxillofacial CT scans
      of trauma patients were reviewed over a five year period, and frontal bone
      fractures were classified: Type 1: Frontal sinus fracture without vertical
      extension. Type 2: Vertical fracture through the orbit without frontal sinus
      involvement. Type 3: Vertical fracture through the frontal sinus without orbit
      involvement. Type 4: Vertical fracture through the frontal sinus and ipsilateral
      orbit. Type 5: Vertical fracture through the frontal sinus and contralateral or
      bilateral orbits. We also identified the depth of skull base extension, and
      performed a chart review to identify associated complications. RESULTS: 149
      frontal bone fractures, including 51 non-vertical frontal sinus (Type 1, 34.2%)
      and 98 vertical (Types 2-5, 65.8%) fractures were identified. Vertical fractures
      penetrated the middle or posterior cranial fossa significantly more often than
      non-vertical fractures (62.2 v. 15.7%, p = 0.0001) and had a significantly higher
      mortality rate (18.4 v. 0%, p < 0.05). Vertical fractures with frontal sinus and
      orbital extension, and fractures that penetrated the middle or posterior cranial
      fossa had the strongest association with intracranial injuries, optic neuropathy,
      disability, and death (p < 0.05). CONCLUSIONS: Vertical frontal bone fractures
      carry a worse prognosis than frontal bone fractures without a vertical pattern.
      In addition, vertical fractures with extension into the frontal sinus and orbit,
      or with extension into the middle or posterior cranial fossa have the highest
      complication rate and mortality.

PMID- 25778873
TI  - Microsurgical reconstruction of the maxilla: Algorithm and concepts.
AB  - INTRODUCTION: The main purpose of this article is to highlight free tissue
      transfers as the first-choice method for three-dimensional (3D) maxillary
      reconstruction, particularly in providing enough bone for palate and maxillary
      arch reconstruction and consequently an implant-retained prosthesis. To achieve
      this, the myosseous free iliac crest was selected whenever possible as the first
      choice inside the reconstructive algorithm and free flap armamentarium. A new
      maxillectomy classification and algorithm reconstruction are proposed. Technical
      modifications and improvements accomplished over time are discussed, considering
      palate, dental implants and prosthesis, nasal sidewall, cranial base and dura, as
      well as recipient vessels. We present functional and aesthetic outcomes of the
      senior author's past 24-year experience (H. C.) with complex midface
      reconstructions. MATERIAL AND METHODS: The authors report and analyse a 24-year
      experience with 57 midface defects in 54 patients (30 males and 24 females). A
      total of 57 maxillary defects - classified as Class I (limited maxillectomy) =
      12, Class II (subtotal maxillectomy) = 15, Class III (total maxillectomy) = 19
      and Class IV (orbitomaxillectomy) = 11 - were analysed regarding sex, age, tumour
      recurrence, free flap, reconstruction and necrosis. In addition, functional
      outcomes were evaluated regarding diet, speech, globe position and vision, while
      aesthetic outcomes were evaluated by patient and surgeon scores. RESULTS: A total
      of 52 free flaps were performed in 47 patients; three patients were operated upon
      twice; and two other patients needed two sequentially linked flow-through flaps.
      The free flap survival was 96% with two total flap losses (4%). The other seven
      patients were fitted with a soft tissue-retained obturator prosthesis.
      CONCLUSIONS: Microsurgical vascularised osteomyocutaneous free flaps are actually
      the gold standard for reconstruction of complex defects following maxillectomy.
      This algorithm is based on the anatomofunctional defect of the maxilla and it
      facilitates flap selection, which is a must.

PMID- 25778874
TI  - Maxillary growth after maxillary protraction: Appliance in conjunction with
      presurgical orthopedics, gingivoperiosteoplasty, and Furlow palatoplasty for
      complete bilateral cleft lip and palate patients with protruded premaxilla.
AB  - BACKGROUND AND AIMS: In bilateral cleft lip and palate (BCLP) with premaxillary
      protrusion, a good outcome with adequate maxillary development is difficult to
      achieve. The purpose of this article is to evaluate the maxillary growth after
      using presurgical orthopedics (PSO), gingivoperiosteoplasty (GPP), Furlow
      palatoplasty, and maxillary protraction appliance (MPA) for BCLP with
      premaxillary protrusion. PATIENTS AND METHODS: Seven patients with complete BCLP
      with premaxillary protrusion were treated by PSO, cheiloplasty, GPP, and Furlow
      palatoplasty. MPA was used as part of the protocol for 6 months to 1 year for
      postoperative retardation of maxillary growth cases. Maxillary growth was
      evaluated by cephalometric analysis at 4 and 10 years of age, and bone formation
      at the alveolar cleft was evaluated by computed tomography (CT) imaging at 5
      years of age. RESULTS: At 4 years of age, three of seven patients had apparent
      retardation of maxillary growth. The maxillary growth at 10 years of age was
      equivalent to the average value of normal Japanese after using MPA in three
      cases. At 5 years of age, only two of seven patients showed sufficient bone
      formation at the alveolar cleft to avoid alveolar bone grafting (ABG).
      Subsequently, ABG was performed in five patients. DISCUSSION: Although three of
      seven patients had apparent crossbite at 4 years of age, the maxillary growth of
      all patients at 10 years of age was approximately equivalent to the average value
      of normal Japanese after using MPA. A treatment protocol based on PSO, GPP,
      Furlow palatoplasty, and MPA may be an option, but long-term growth is unknown.

PMID- 25778876
TI  - Dirac dispersion in photonic hypercrystals.
AB  - Photonic hypercrystals--the recently introduced concept of artificial optical
      media that combines the properties of hyperbolic metamaterials and photonic
      crystals [E. Narimanov, Phys. Rev. X, 2014, 4, 041014]--can support Dirac cone
      dispersion at a finite frequency.

PMID- 25778875
TI  - Direct delayed breast reconstruction with TAP flap, implant and acellular dermal
      matrix (TAPIA).
AB  - BACKGROUND: The latissimus dorsi (LD) flap is considered one of the working
      horses within the field of breast reconstruction and it offers several
      advantages. However, donor-site morbidity may pose a problem. This article
      describes a new and modified technique for delayed breast reconstruction
      combining the use of a propeller thoracodorsal artery perforator (TAP) flap with
      an acellular dermal matrix (ADM) and an implant. METHODS: The paper presents 43
      delayed breast reconstructions in 38 women using a modified technique for
      harvesting the TAP flap in combination with an ADM and an implant for total
      breast reconstruction. The focus of this paper is the refinements of our
      technique and short-term outcome in complication rates. The data presented were
      collected retrospectively. RESULTS: Three patients experienced major
      complications including hematoma, partial flap necrosis, and venous congestion.
      In addition, seven patients experienced minor complications including small
      partial flap necrosis and epidermolysis. There were no cases of infection and all
      flaps survived. The reconstructive goal was achieved in a single-stage procedure
      in all but one, 42/43 cases (98%). CONCLUSIONS: The propeller TAP flap combined
      with an ADM and an implant can safely be used for delayed breast reconstruction.
      The technique offers a single-stage reconstruction and the donor-site morbidity
      is limited. The method is safe and reliable with complication rates comparable to
      those of similar methods. Although there is a learning curve, this simple
      modified technique does not demand any perforator or other vessel dissection. Any
      trained plastic surgeon should be able to adopt the technique into the growing
      armamentarium of breast reconstruction possibilities.

PMID- 25778877
TI  - A fast and switchable microfluidic mixer based on ultrasound-induced vaporization
      of perfluorocarbon.
AB  - Mixing two fluids together within a microfluidic device still remains a
      challenging operation today. In order to achieve this goal, a number of effective
      micromixers have been developed over the years based on the use of either passive
      or active systems. Typically, passive mixers require no external energy, are more
      robust, and are easy to manufacture albeit they are poorly flexible. Active
      mixers, on the other hand, rely on external disturbance and are thus more
      difficult to use but are proven to have greater efficacy. Here, we report a
      particularly effective, remotely induced and switchable microfluidic mixer, which
      relies on the concomitant use of ultrasound and a perfluorocarbon (PFC) phase,
      with the latter benefiting from its immiscibility with most fluids and its low
      boiling point. More specifically, our approach is based on localized vaporization
      of a PFC phase at the focal zone of a transducer leading to efficient mixing of
      two adjacent fluids. The results show that mixing occurs ~100 ms following the
      delivery of the acoustic pulse, while a laminar flow is re-established on roughly
      the same time scale. Overall, this method is simple and effective, does not
      require tailored channel geometries, is compatible with both hydrophilic and
      hydrophobic microfluidic systems, and is applicable to a wide range of Reynolds
      numbers (10(-4) < Re < 2.10(0)), and the PFC phase can be easily separated from
      the mixed phase at the end of the run. 

PMID- 25778878
TI  - Trace phase formation, crystallization kinetics and crystallographic evolution of
      a lithium disilicate glass probed by synchrotron XRD technique.
AB  - X-ray diffraction technique using a laboratory radiation has generally shown
      limitation in detectability. In this work, we investigated the in situ high
      temperature crystallization of a lithium disilicate glass-ceramic in the SiO2
      Li2O-CaO-P2O5-ZrO2 system with the aid of synchrotron radiation. The formation of
      lithium metasilicate and other intermediate phases in trace amount was
      successfully observed by synchrotron X-ray diffraction (SXRD). The
      crystallization mechanism in this glass was thus intrinsically revised to be the
      co-nucleation of lithium metasilicate and disilicate, instead of the nucleation
      of lithium disilicate only. The phase content, crystallite size and
      crystallographic evolutions of Li2Si2O5 in the glass-ceramic as a function of
      annealing temperature were studied by performing Rietveld refinements. It is
      found that the growth of Li2Si2O5 is constrained by Li2SiO3 phase at 580-700
      degrees C. The relationship between the crystallographic evolution and phase
      transition was discussed, suggesting a common phenomenon of structural response
      of Li2Si2O5 along its c axis to other silicon-related phases during glass
      crystallization. 

PMID- 25778880
TI  - [The relationship between induction chemotherapy cycles and prognosis in patients
      with acute myeloid leukemia].
AB  - OBJECTIVE: To explore the relationship between induction chemotherapy cycles to
      achieve complete remission (CR) and prognosis in patients with acute myeloid
      leukemia(AML). METHODS: From April 2004 to December 2013, 397 adult patients with
      newly diagnosed AML (acute promyelocytic leukemia excluded) received the
      idarubicin combined with cytarabine (IA)"3+7" regimen as the first induction
      chemotherapy were enrolled in the study. Therapeutic effect, relapse and survival
      of these patients were discussed. Patients underwent continuous consolidation
      chemotherapy, and some eligible patients received allogeneic hematopoietic stem
      cell transplantation (allo-HSCT) in the first complete remission. RESULTS: Of 397
      patients, 347 evaluable patients achieved CR after 1-4 cycles induction
      chemotherapy.The median follow-up was 18.0 (2.4-115.4) months in survivors, the
      cumulative incidence of relapse (CIR), disease-free survival (DFS) and overall
      survival (OS) at 3 years were 33.0%, 58.6% and 67.1%, respectively. Multivariate
      analysis revealed that unfavorable cytogenetics, more cycles to achieve CR and
      post-remission treatment without allo-HSCT were independent risk factors
      affecting DFS and OS. FLT3-ITD mutation positive was another independent risk
      factor affecting DFS. There was no statistic difference between patients who
      achieved CR after one cycle (n=255) and two cycles (n=73) treatment in DFS and OS
      (P>0.05). DFS and OS in patients who achieved CR after 3 or 4 cycles(n=19)were
      significantly lower than the above two groups (P<0.05). Multivariate analysis
      among 183 patients who received consistent chemotherapy showed that achieving CR
      within 2 cycles was the favorable factor affecting DFS and OS (P=0.001, P=0.035).
      CONCLUSION: Achieving CR within 2 cycles of induction chemotherapy was associated
      with better prognosis among adult CR patients with AML.

PMID- 25778879
TI  - Inhibition of autophagy overcomes glucocorticoid resistance in lymphoid malignant
      cells.
AB  - Glucocorticoid (GC) resistance remains a major obstacle to successful treatment
      of lymphoid malignancies. Till now, the precise mechanism of GC resistance
      remains unclear. In the present study, dexamethasone (Dex) inhibited cell
      proliferation, arrested cell cycle in G0/G1-phase, and induced apoptosis in Dex
      sensitive acute lymphoblastic leukemia cells. However, Dex failed to cause cell
      death in Dex-resistant lymphoid malignant cells. Intriguingly, we found that
      autophagy was induced by Dex in resistant cells, as indicated by autophagosomes
      formation, LC3-I to LC3-II conversion, p62 degradation, and formation of acidic
      autophagic vacuoles. Moreover, the results showed that Dex reduced the activity
      of mTOR pathway, as determined by decreased phosphorylation levels of mTOR, Akt,
      P70S6K and 4E-BP1 in resistant cells. Inhibition of autophagy by either
      chloroquine (CQ) or 3-methyladenine (3-MA) overcame Dex-resistance in lymphoid
      malignant cells by increasing apoptotic cell death in vitro. Consistently,
      inhibition of autophagy by stably knockdown of Beclin1 sensitized Dex-resistant
      lymphoid malignant cells to induction of apoptosis in vivo. Thus, inhibition of
      autophagy has the potential to improve lymphoid malignancy treatment by
      overcoming GC resistance. 

PMID- 25778881
TI  - [Effect of immunoglobulin heavy/light chain detection on the minimal residual
      disease monitoring in IgG multiple myeloma patients].
AB  - OBJECTIVE: To evaluate the specificity and sensitivity of immunoglobulin
      heavy/light chain (HLC) and serum free light chain (FLC) level in minimal
      residual disease monitoring of IgG type multiple myeloma (MM) patients during
      complete remission (CR). METHODS: Immunoglobulin HLC was assessed in 20 IgG
      myeloma patients by immune turbidimetry using SPAplus Analyzer. The serum level
      of HLC and FLC was detected at same time. Combine with those obtained by serum
      protein electrophoresis (SPE) and immune fixation electrophoresis (IFE), the
      specificity and sensitivity of HLC in detection of serum immunoglobulin were
      analyzed. Combined with the clinical efficacy, kappa/lambda ratios of HLC (rHLC)
      and FLC (rFLC) were compared between the patients and normal controls. RESULTS:
      Among 20 patients, there were 10 male and 10 female, the median age was 56 years
      (35-70). There were 6 patients with abnormal rHLC but normal rFLC; 3 patients
      with abnormal rFLC but normal HLC; and 11 patients with both normal rHLC and
      rFLC. During the mean follow-up time of 18 months, 4 of the6 patients with
      abnormal rHLC accepted intervention therapies, 1 case relapsed in 9 months,the
      other 2 untreated patients relapsed in 3 months. Among the 3 cases with abnormal
      rFLC, 2 patients are still in remission after intervention therapies,the other
      untreated patient relapsed in 1.5 months. Among the 11 untreated patients with
      both normal rHLC and rFLC, 3 relapsed with the disease free survival time of 3.5
      months, 5.0 months and 5.5 months respectively. CONCLUSION: The combined
      detection of HLC and FLC is helpful to assess the curative efficacy and the
      accuracy of minimal residual disease monitoring, and more effectively evaluate
      the prognosis of MM patients. Abnormal rHLC and rFLC are correlated with poor
      prognosis, while early intervention therapies can help to improve disease free
      survival.

PMID- 25778882
TI  - [Classification of amyloidosis by laser micro-dissection and mass spectrometry
      based proteomic analysis].
AB  - OBJECTIVE: To establish a novel method to determine specific type of amyloidosis
      through laser microdissection and mass spectrometry (LMD/MS) based proteomic
      analysis. METHODS: There were 138 formalin-fixed and paraffin-embedded (FFPE)
      biopsy samples of patients who were diagnosed as systemic amyloidosis used in
      this study. For each case, a 10 MUm section stained with congo-red and positive
      amyloid deposits were identified under fluorescent light, followed by micro
      dissection and mass spectrometry analysis. The amyloidosis subtype was confirmed
      based on the most abundant amyloid protein. RESULTS: The tissue types of 138
      specimens were as following: subcutaneous abdominal fat accounted for 26%, tongue
      for 19%, gingiva for 11%, kidney for 9%, intestine for 9%, heart for 6% and
      others for 20%. Specific types of amyloid were accurately detected in 121 cases,
      including 106 (87.6%) amyloid light chain (AL) type, 7 (5.8%) amyloid trans-thy
      retin (ATTR), 2 (1.7%) amyloidogenic protein A (AA), 2 (1.7%) amyloid heavy chain
      (AH)/AL+AH, 2 (1.7%) fibrinogen alpha chain (AFib), 1(0.8%) amyloid
      apolipoprotein A-type II (AApoA-II) and one (0.8%) amyloid lysozyme (ALys).
      Diagnosis of amyloidosis was excluded in 5 cases. The types of twelve cases were
      indeterminate by LMD/MS. On the whole, LMD/MS reached 91.3% accuracy rate in
      amyloid typing. Commonly involved organs (for example, heart, kidney and liver)
      turned out to be suitable sources of FFPE samples with typing success rate of
      almost 100%. In contrast, MS analysis was successful in only 83.3% of
      subcutaneous abdominal fat samples. CONCLUSION: LMD/MS method provided a more
      direct technique for accurate typing of amyloidosis in a single procedure.

PMID- 25778883
TI  - [A multicenter clinical trial of caffeic acid tablet in treatment of 103 primary
      immune thrombocytopenia patients].
AB  - OBJECTIVE: To determine the efficacy and safety of oral caffeic acid (CA) tablet
      in management of primary immune thrombocytopenia(ITP). METHODS: One hundred and
      three ITP patients with PLT>10*109/L and no serious bleeding symptoms from three
      centers were enrolled. According to their platelet count before CA treatment,
      these patients were divided into group A (PLT<30*109/L), including 24 females and
      27 males with median age 48(18-84)years; and group B (PLT>=30*109/L), including
      33 females and 19 males with median age 43(18-83)years. Patients in both groups
      took CA tablets orally of 300 mg three times per day for 12 consecutive weeks.
      Combined medicine treatment such as corticosteroids, danazol, TPO and Rituximab,
      which might increase the platelet count of these patients, were not allowed
      during CA therapy. RESULTS: In group A, the overall response rate was
      51.0%(26/51), with 2 patients achieving complete response (CR) and 24 patients
      achieving response(R). Of 26 patients achieving response (CR+R), the median
      platelet count before CA therapy was 20.5(15-28)*109/L , and the median peak
      platelet count after CA therapy was 63(38-112)*109/L. The median time to
      achieving response was 4(2-10) weeks. Patients with pretreatment PLT>20*109/L
      showed significantly better response than those PLT<20*109/L (68.0% vs 34.6%,
      P=0.017). In group B, the CR rate was 40.4%(21/52). Frequency of CA-related
      adverse events was 1.94%(2/103), including mild nausea in 1 case and elevation of
      liver enzymes in 1 case. Both were grade 1 and transient. CONCLUSION: Caffeic
      acid was effective in patients with ITP with few and mild adverse effects.

PMID- 25778884
TI  - [A single-center clinical study of 22 patients with acquired hemophilia].
AB  - OBJECTIVE: To investigate the feature of underlying disorders, clinical symptoms,
      diagnosis and treatment strategies of patients with acquired hemophilia(AH).
      METHODS: The clinical data and laboratory tests results of 22 patients with AH
      from March 2010 to June 2014 were retrospectively analyzed. RESULTS: A total of
      22 patients with AH were enrolled in our study, including 20 patients diagnosed
      as acquired hemophilia A (AHA) and 2 as acquired hemophilia B (AHB). Among the
      AHA patients, there were 10 males and 10 females with the median age of 37.5
      (range, 2-95) years old. The median activity of FVIII (FVIII:C) of the 20 AHA
      patients was 1.9% (0.5%-39.0%). Soft tissue hematoma (80.0%) and subcutaneous
      bleeding (75.0%) were the most common clinical symptoms. Two male children were
      diagnosed as AHB (age 1 and 3 years old, respectively) with mild bleeding
      symptoms, and the activities of FIX (FIX:C) were 5.0% and 16.0%, respectively. In
      addition, an underlying disorder was found in 7 patients (31.8%). In laboratory
      testing, all patients had prolonged APTT, normal PT, decreased FVIII:C or FIX:C,
      positive antibody screening test or antibody titer (2-32 BU), and negative for
      lupus anticoagulant and anticardiolipin antibody. Nineteen out of 20 patients
      were treated with blood products to stop acute bleeding episodes. Corticosteroid
      alone was applied to 7 patients, corticosteroid combined with other
      immunosuppressive agents to 11 patients, rituximab to 3 patients. Nineteen
      patients responded well to hemostatic treatment, except 1 patient who died of
      fatal bleeding. The FVIII:C of 8 patients increased to a normal level with the
      median time of 42.5(21-145) days. After treatment, the activity of FIX:C of the 2
      AHB patients achieved 35% and 24% in 48 and 60 days, respectively. CONCLUSION:
      Acquired hemophilia is not an uncommon disease in clinical practices, which can
      occur in people of all ages. AH is a bleeding disorder with heterogeneous
      characteristics. Compared with adult, the clinical symptoms of children patients
      were mild, which lead to underdiagnosis.

PMID- 25778885
TI  - [Gene analysis in a family of hereditary hemorrhagic telangiectasia].
AB  - OBJECTIVE: To investigate the clinical feature of a family with hereditary
      hemorrhagic telangiectasia (HHT), and to study the mutation of its related genes.
      METHODS: Medical histories of the family were analyzed to detect HHT patients
      according to the diagnostic criteria. ENG and ALK-1 genes of the proband and her
      two daughters were analyzed. DNA from the three patients' peripheral blood was
      extracted. The exons 2-10 and their intron-exon boundaries of ALK1 were amplified
      with PCR, and then the PCR products were sequenced and analyzed to identify the
      mutation. RESULTS: There were 11 people in 41 family members of 4 generations
      were diagnosed as HHT. The proband and her two daughters suffered from multiple
      organ damage, the younger daughter appeared only imaging features instead of
      corresponding clinical symptoms. A missense mutation at the 1321 bp of cDNA
      (c.1321G>A) was detected in the exon 9 of ALK1, which resulted in valine 441 to
      methionine replacement in ALK-1 protein (p.Val441Met). CONCLUSION: A Chinese
      family with HHT was studied and a missense mutation (c.1321G>A, p.Val441Met) of
      ALK-1 was discovered. This mutation is the genetic basis of the family with HHT
      and is reported for the first time in China. This research will not only help to
      further investigate molecular mechanism of pathogenesis of HTT, but also provide
      evidences and references for the following gene screening and genetic counseling
      on HTT family members.

PMID- 25778886
TI  - [Effect of chronic graft versus host disease on relapse and survival in patients
      with acute myeloid leukemia].
AB  - OBJECTIVE: To explore the influence of relapse and survival by chronic graft
      versus host disease (cGVHD) in patients with acute myeloid leukemia (AML) after
      allogeneic hematopoietics stem cell transplantation (allo-HSCT). METHODS: Fifty
      five AML patients received allo-HSCT were retrospectively reviewed. Relapse rate
      and overall survival (OS) were analyzed according to cGVHD. RESULTS: cGVHD
      significantly decreased the relapse rate of AML patients after transplantation
      within 2 years when compared with those without cGVHD (8.7% vs 38.6%, P=0.019),
      however, cGVHD had no effect on the long-term relapse rate (22.8% vs 5.9%,
      P=0.217). cGVHD had no effect on OS within 2 years (78.3% vs 61.0%, P=0.155) but
      could decrease the rate of long-term survival (63.7% vs 100%,P=0.01). cGVHD also
      could reduce the rate of relapse (8.3% vs 46.2%, P=0.044) and enhanced the rate
      of survival (83.3% vs 47.2%, P=0.045) in patients with high risk AML after allo
      HSCT in 2 years, while it had no effect on the relapse rate and OS in patients
      with low and intermediated risk AML in early and late phase. Moreover, compared
      with the rate of relapse(38.6%) in patients without cGVHD, the rate of relapse
      were lower in patients with limited cGVHD and intensive cGVHD (27.3% and 31.3%,
      respectively) but the long-term survival was significantly lower (53.3%, P=0.001)
      in those patients with intensive cGVHD after all-HSCT. CONCLUSION: The benefit
      effect of cGVHD mainly took place within 2 years after allo-HSCT in AML patients
      especially in those with high risk, while in late phase after allo-HSCT, cGVHD
      especially intensive cGVHD had an effect on reducing long-term survival.

PMID- 25778887
TI  - [Retrospective efficacy analysis of decitabine bridging allogeneic hematopoietic
      stem cell transplantation on the treatment of myelodysplastic syndrome].
AB  - OBJECTIVE: To evaluate the efficacy of decitabine (DAC) bridging therapy followed
      by allogeneic hematopoietic stem cell transplantation (allo-HSCT) in patients
      with myelodysplastic syndrome (MDS). METHODS: The clinical characteristics and
      curative effect of MDS patients who received allo-HSCT from 2010 July to 2013
      December were retrospectively analyzed. Of them, 25 MDS patients who received
      decitabine bridging allo-HSCT were randomly selected (referred to as the bridging
      group),while at the same time another 33 MDS patients who did not receive
      decitabine for allo-HSCT in MDS were also randomly selected as control group. The
      effect of decitabine bridging allo-HSCT on the patients' survival and occurrence
      of graft versus host disease (GVHD) was analyzed. RESULTS: With decitabine bridge
      therapy, 64.0% patients (16/25) achieved marrow complete remission before allo
      HSCT, while the control group was only 15.1% (5/33, P<0.05). Decitabine bridging
      group of early transplant-related mortality was lower than that of the control
      group (4.0% vs 18.2%), but the difference was not statistically significant
      (P=0.106). Up to follow-up deadline, the mortality of decitabine bridging group
      was 12.0%, while that of the control group was 30.3% (P<0.05). The 2-year OS of
      decitabine bridging group was 83.0%, while that of the control group was 59.0%
      (P<0.05). Of the 14 patients in decitabine bridging group with aGVHD, 7 was grade
      IaGVHD, 3 grade II and 4 grade III. Of the 16 patients in control group with
      aGVHD, 7 was grade IaGVHD, 8 grade II and 1 grade III. CONCLUSION: Decitabine
      bridging therapy followed by allo-HSCT in the treatment of MDS is safe and
      effective.

PMID- 25778888
TI  - [Potential relationship and clinical significance of miRNAs and Th17 related
      cytokines in patients with multiple myeloma].
AB  - OBJECTIVE: To explore the expression and significance of miRNAs and Th17 related
      cytokines in patients with multiple myeloma (MM). METHODS: A total of 27 MM
      patients and 8 health controls were enrolled in this study. The expression of miR
      15a/16,miR-34a,miR-194-2-192 cluster and miR-181a/b in bone marrow were detected
      by real-time quantitative PCR (qRT-PCR). Enzyme-linked immunosorbent assay
      (ELISA) was used to determine the levels of Th17 related cytokines interleukin-17
      (IL-17), IL-21, IL-22, IL-23 and IL-27 in peripheral blood plasma. The role of
      miRNAs and Th17 related cytokines was analyzed in the development of MM. RESULTS:
      The expression of miR-15a/16,miR-34a,miR-194-2-192 cluster in MM patients were
      significantly lower than those of the health controls, while miR-181a/b were
      exactly the reverse (P<0.05). The levels of IL-17, IL-21 and IL-27 were up
      regulated in MM patients compared to health controls while IL-22 was down
      regulated (P<0.05). There was no significant difference of IL-23 between the two
      groups. The levels of miRNAs and Th17 related cytokines had associated with ISS
      but not with some clinical parameters (such as gender, age, disease
      classification). Higher expression of IL-17, IL-21, IL-23, IL-27, miR-181a/b and
      lower expression of miR-15a/16,miR-34a,miR-194 and IL-22 were observed in the end
      stage than the early stage of MM patients (P<0.05). There was a significant
      correlation between miRNAs and Th17 related cytokines. CONCLUSION: Up-regulated
      IL-17, IL-21 and IL-27 may potentially down-regulate the expression of several
      miRNAs in MM patients. Establishment of the relationship may be useful for
      understanding the pathogenesis of MM and for clinical diagnosis of the disease.

PMID- 25778889
TI  - [Study on the molecular mechanisms of a novel large deletion of FXIIIA mRNA in a
      new hereditary factor XIII deficiency].
AB  - OBJECTIVE: To investigate the mechanisms of DelCD11-279 of factor XIII subunit A
      mRNA in the pathogenesis of hereditary factor XIII deficiency. METHODS: The
      recombinant plasmids containing pET-22b(+)/FXIIIA of normal subject and proband's
      mother and pET-22b(+)/FXIIIA-Del of the proband were constructed and transformed
      into E. coli BL21. Expressing protein was analyzed by the SDS-PAGE and purified
      by Ni-NTA resin. Purified proteins were detected by the Western-blot. The
      activity of purified protein was detected by the incorporation test with EZ
      LinkTM5-(Biotinamido) Pentylamine. RESULTS: The recombinant plasmids containing
      pET-22b(+)/FXIIIA and pET-22b(+)/FXIIIA-Del which constructed and identified
      successfully by enzyme digestion and PCR, were transformed into E. coli BL21 and
      efficiently expressed by IPTG induction. The molecular weights of expressing
      proteins are 83 200 and 51 900 by the SDS-PAGE. Expressing proteins were purified
      by Ni-NTA resin, and were proved to be human FXIIIA proteins by Western-blot.
      Purified protein activity of proband's mother and proband was 95.87% and 0 of the
      purified FXIIIA protein activity from the normal subject, respectively.
      CONCLUSION: DelCD11-279 of FXIIIA mRNA which encoding a 464 amino acids of
      inactive FXIIIA protein is one of the molecular mechanisms resulting in FXIII
      deficiency in the patient.

PMID- 25778890
TI  - [A clinicopathological analysis of 160 cases of adult Langerhans cell
      histiocytosis].
AB  - OBJECTIVE: To observe the clinical features of Langerhans cell histiocytosis
      (LCH), and to improve its early diagnosis and treatment. METHODS: Retrospective
      analysis of 160 cases of adult LCH from pathology department, West China Hospital
      of Sichuan University and Union Hospital of Tongji Medical College of Huazhong
      University of Science and Technology from January 1992 to December 2013 were
      performed, and their clinical features were analyzed. RESULTS: Of 160 cases,
      there were 110 male and 50 female, the male to female ratio was 2.2:1. The mean
      age was 35(18-73) years. There were total 222 lesion sites, including 172(77.5%)
      osteal lesions, followed by 13(5.8%) lymph nodes and 8(3.6%) oral cavity lesions.
      The other involved organs were skin(5, 2.2%), liver(5, 2.2%), fossa orbitalis(4,
      1.8%), lungs(4, 1.8%), sternoclavicular joint(3, 1.4%), gastrointestinal(2,
      0.9%), ear(2, 0.9%), and thyroid (2, 0.9%), adrenal gland (1, 0.5%) and
      sublingual gland (1, 0.5%). Of 160 cases, 150 (93.8%) had one organ involved
      while 10 (6.2%) had two or more organs involved. Clinically, 77 cases (48.1%)
      were misdiagnosed as bone tumors (28 cases, including giant cell tumor, fibrous
      dysplasia, chondroblastoma, osteoblastoma and osteosarcoma), bone tuberculosis
      (13 cases), meningioma(9 cases), bone cysts (5 cases), chronic osteomyelitis (5
      cases) and diabetes insipidus (5 cases) , skin (4 cases) diseases malignant
      lymphoma (4 cases), chronic skin ulcers (4 cases), chronic otitis media (1 case),
      lung (1 case) and oral cancer (1 case). CONCLUSION: In this group of the adult
      cases, the ratio of the male patients is higher. Adult LCH occurs predominantly
      in bone and presents mainly as unisystem single-focal disease, but multi-organ
      lesion and skin involvement are lower than that reported in the literatures. Just
      as LCH in children, adult LCH is also easy to be misdiagnosed. We should raise
      awareness of the disease and pathological examination is helpful for early
      diagnosis.

PMID- 25778891
TI  - [Clinical study on 137 cases of unrelated single unit umbilical cord blood
      hematopoietic stem cell transplantation].
AB  - OBJECTIVE: To evaluate relevant prognostic factors of unrelated single unit
      umbilical cord blood hematopoietic stem cell transplantation (sUCBT), and to
      explore the correlation between cryopreservation time of cord blood and cell
      viability and outcome of sUCBT. METHODS: Retrospective analysis of 137 patients
      undergoing sUCBT with cord blood provided by Shanghai Cord Blood Bank from Mar.
      15, 2007 to Dec. 26, 2013 were performed in this study. The mean cryopreservation
      time of 137 units cord blood was 698(96-1968) days, with mean cell viability of
      87.4% after thawing. RESULTS: No statistical difference on cell viability,
      hematopoietic reconstitution, graft failure, acute graft versus host disease
      (GVHD) and overall survival (OS) was found between patients transfused with cord
      blood preserved below and above 2 years. The 5-year OS of patients transfused
      with cord blood preserved below and above 2 years were 55.6% and 67.9%,
      respectively (P=0.124). OS of the UCBT at 2011 and before, and after 2011 was
      48.7% and 79.6%, respectively (P=0.001). Age above 16-year-old (RR=2.830,
      P=0.027) and UCBT at 2011 and before (RR=0.203, P<0.001) were two risk factors of
      treatment related mortality. CONCLUSION: Outcome of sUCBT in China had
      significant improvement in recent 2 years. Cryopreservation time of cord blood
      had no statistical correlation to cell viability after thawing and clinical
      outcome.

PMID- 25778892
TI  - [Analysis of blood cell autophagy distribution in hematologic diseases by
      transmission electron microscope].
AB  - OBJECTIVE: To investigate the distribution characteristics of blood cells
      autophagy in hematologic diseases, as well as their possible pathomechanism.
      METHODS: Retrospective analysis of electron microscopy specimens of 3 277
      patients with hematological diseases were performed. The blood cells autophagy
      was observed by transmission electron microscopy, and its distribution
      characteristics were analyzed. The pathomechanism of blood cell autophagy was
      explored in combination with clinical examination and diagnosis. RESULTS: There
      were 15 samples were found to have mature granulocytes or nucleated erythrocytes
      autophagy. Of them, 6 cases were myelodysplastic syndrome (MDS), 2 acute
      leukemia, 1 in each of aplastic anemia, pure red cell aplastic anemia,
      thalassemia, iron deficiency anemia, lymphoma, multiple myeloma and polycythemia
      vera. Among 15 cases, 11 cases were found to have mature granulocytes autophagy,
      4 cases nucleated erythrocytes autophagy. Besides autophagy, apoptosis occurred
      in 9 cases, cytolysis in 6 cases, megaloblastic change in 5 cases. CONCLUSION:
      Mature granulocytes or nucleated erythrocytes autophagy occurred more frequently
      in MDS among hematologic diseases, dyshaematopoiesis including apoptosis,
      cytolysis and megaloblastic change could induce autophagy function enhancement.

PMID- 25778893
TI  - [Effect of ERK1/2 inhibitor AZD8330 on human Burkitt's lymphoma cell line Raji
      cells and its mechanism].
AB  - OBJECTIVE: To investigate the effect of ERK1/2 inhibitor AZD8330 on human
      Burkitt's lymphoma cell line Raji cells and its mechanism. METHODS: Raji cells
      were treated with different concentrations of AZD8330. CCK-8 was used to detect
      the cell viability. The apoptosis rate of Raji cells was detected by flow
      cytometry using Annexin V/PI-staining. Real-time PCR was used to assess the
      expression of Bcl-2, Bcl-xl, caspase-3 and VEGF genes. The protein expression
      level of Bcl-2, Bcl-xl, caspase-3 and p-ERK1/2 was tested with Western blot.
      RESULTS: The cell survival rate decreased to(62.09+/-0.86)%,(50.06+/-1.33)% and
      (39.13+/-2.34)% respectively after cells were treated with AZD8330 at 1.00
      MUmol/L in vitro for 24 h, 48 h and 72 h, and statistically significant
      differences were observed in groups with different time of treatment(P<0.05).
      Apoptosis of cells treated with AZD8330 at 0.10, 1.00, 10.00 MUmol/L in vitro for
      24 h, 48 h and 72 h was analyzed, and the statistically significant differences
      were observed in groups of different time and concentration treatment (P<0.05).
      AZD8330 induced Raji cell apoptosis and upregulated expression of Bcl-2, Bcl-xl,
      VEFG and decreased the expression of caspase-3 in a dose and time dependent
      manner, and statistically significant differences were observed in groups of
      different time and concentration treatment (P<0.05). At the same time, the Bcl-2,
      Bcl-xl and p-ERK1/2 proteins expression is suppressed obviously, but the
      expression of caspase-3 protein increased. CONCLUSION: AZD8330 induces cell
      apoptosis by down-regulating the activation of ERK1/2 signal transduction pathway
      in Burkitt's lymphoma cell line Raji cells in a dose and time dependent manner.

PMID- 25778894
TI  - [Effect of ursolic acid on proliferation of T lymphoma cell lines Hut-78 cells
      and its mechanism].
AB  - OBJECTIVE: To investigate the effects of ursolic acid on T cell lymphoma cell
      lines-Hut-78 cells and its mechanism. METHODS: Inhibition of Hut-78 cells
      proliferation by ursolic acid at different concentration (10, 20, 40 and 80
      MUmol/L) for different incubation time (4, 12, 24, 48 and 72 h)was examined by
      MTT method, and early apoptosis by flow cytometry. The protein expressions of
      p65, p50, p52 and p100, and caspase-8, caspase-3 and caspase-9 were detected by
      Western blot. VEGF and COX-2 mRNA expressions were measured by reverse
      transcription polymerase chain reaction (RT-PCR). RESULTS: It was showed that
      ursolic acid inhibited proliferation of Hut-78 cells (P<0.05). Apoptosis of Hut
      78 cells was induced by 10, 20, 40 and 80 MUmol/L ursolic acid treatment
      (P<0.01). Likewise, expression of p65 and p50 proteins were down-regulated by
      ursolic acid treatment (10, 20, 40 and 80 MUmol/L) (P<0.01), but there was no
      significant change in the expression of p52 and p100. Moreover, ursolic acid
      could up-regulate expression of caspase-8, caspase-3 and caspase-9 protein
      (P<0.01). RT-PCR examination showed that VEGF and COX-2 mRNA expression decreased
      by ursolic acid treatment. CONCLUSION: Inhibition of Hut-78 cells proliferation
      may be related to ursolic acid induced apoptosis through h death receptors and
      mitochondrial pathways. NF-kappaB classical signal pathway may be one of its
      mechanisms, and VEGF and cox-2 may also be involved.

PMID- 25778895
TI  - [Recombinant factor VIIa for the treatment of acute promyelocytic leukemia with
      severe bleeding: 8 cases report and literature review].

PMID- 25778896
TI  - [A clinical analysis of adenovirus infection after allogeneic stem cell
      transplantation in 3 patients].

PMID- 25778897
TI  - [Genetic diagnosis and bioinformatic analysis of a pedigree with inherited factor
      VII deficiency].

PMID- 25778898
TI  - [Study of IFN-alpha in combination with all-trans retinoic acid on the
      proliferation and differentiation of acute promyelocytic leukemia cell lines NB4
      and NB4-R1 cells].

PMID- 25778899
TI  - [Metabolic regulation of bone marrow microenvironment on hematopoietic stem cells
      and its role in hematologic diseases].

PMID- 25778900
TI  - [Advances in prediction and diagnostic biomarkers on acute graft-versus-host
      disease after allogeneic stem cell transplantation].

PMID- 25778901
TI  - Sestrin2-AMPK activation protects mitochondrial function against glucose
      deprivation-induced cytotoxicity.
AB  - Sestrin2 (SESN2) regulates redox-homeostasis and apoptosis in response to various
      stresses. Although the antioxidant effects of SESN2 have been well established,
      the roles of SESN2 in mitochondrial function and metabolic stress have not yet
      been elucidated. In this study, we investigated the role of SESN2 in
      mitochondrial dysfunction under glucose deprivation and related signaling
      mechanisms. Glucose deprivation significantly upregulated SESN2 expression in
      hepatocyte-derived cells. Antioxidant treatments repressed SESN2 induction under
      glucose deprivation, this result suggested that reactive oxygen species (ROS)
      production was involved in SESN2 induction. Moreover, NF-E2-related factor-2
      (Nrf2) phosphorylation was accompanied in induction of SESN2 by glucose
      deprivation. To elucidate the functional role of SESN2, we examined cells that
      stably overexpressed SESN2. Overexpression of SESN2 inhibited glucose deprivation
      induced ROS production and cell death. In addition, under glucose deprivation,
      the changes in mitochondrial membrane potential, ADP/ATP ratio, and mitochondrial
      DNA content were significantly restored in SESN2-overexpressing cells. Moreover,
      siRNA knockdown of SESN2 failed to prevent mitochondrial permeability transition
      by glucose depletion. Mechanistic investigation showed that glucose deprivation
      significantly increased AMP-activated protein kinase (AMPK) activation. The
      recovery of mitochondrial function under glucose deprivation in SESN2
      overexpressing cells was not seen in SESN2-overexpressing cells transfected with
      a dominant-negative AMPK; this result suggested that AMPK activation was
      responsible for SESN2-mediated mitochondrial protection against glucose
      deprivation. Treatment with 5-aminoimidazole-4-carboxamide-1-beta-D
      ribofuranoside (AICAR, an AMPK activator) also provided cytoprotective effects
      against glucose deprivation. Our findings provide evidence for the functional
      importance of SESN2-AMPK activation in the protection of mitochondria and cells
      against glucose deprivation-induced metabolic stress. 

PMID- 25778902
TI  - Pyruvate kinase M2 accelerates pro-inflammatory cytokine secretion and cell
      proliferation induced by lipopolysaccharide in colorectal cancer.
AB  - Surgery-induced inflammation has been associated with cancer recurrence and
      metastasis in colorectal cancer (CRC). As a constituent of gram-negative
      bacteria, lipopolysaccharide (LPS) is frequently abundant in the peri-operative
      window. However, the definite roles of LPS in tumour progression remain elusive.
      Here we reported that LPS treatment increased PKM expression through activation
      of NF-kappaB signalling pathway, and knockdown of PKM reversed LPS-induced TNF
      alpha, IL-1beta production and cell proliferation in CRC cells. We further showed
      that the PKM2 but not PKM1 mediated the pro-inflammatory and proliferative
      effects of LPS. Interestingly, LPS promoted PKM2 binding to the STAT3 promoter to
      enhance STAT3 expression and its subsequent nuclear translocation. Depletion of
      STAT3 decreased PKM2-induced TNF-alpha and IL-1beta expression, indicating that
      STAT3 mediates the pro-inflammatory effects of PKM2. Furthermore, it is the
      protein kinase activity but not the pyruvate kinase activity of PKM2 that is
      required for inflammatory cytokine production. Collectively, our findings reveal
      the NF-kappaB-PKM2-STAT3 axis as a novel mechanism for the regulation of TNF
      alpha and IL-1beta production and suggest the importance of PKM2 as a key
      inflammatory mediator in inflammatory microenvironment. 

PMID- 25778903
TI  - PKCepsilon-mediated c-Met endosomal processing directs fluctuant c-Met-JNK
      paxillin signaling for tumor progression of HepG2.
AB  - Hepatocyte growth factor (HGF) induced c-Met signaling play critical roles in the
      progression of hepatocellular carcinoma (HCC). However, c-Met targeting
      approaches suffered resistance and side effect, thus identification of more
      suitable downstream targets is needed. Recently, we demonstrated HGF-induced
      fluctuant ERK/paxillin signaling within 24h. We further examined the underlying
      mechanisms for fluctuant c-Met/JNK/paxillin signal cascade within 12h. HGF
      induced phosphorylation of c-Met, JNK, and paxillin (Ser178) shared a common
      fluctuation pattern characterized by an initial peak at 0.5h, a middle drop at
      4h, and a later peak at 10h. Dynasore, the inhibitor of dynamin, suppressed HGF
      induced c-Met internalization and phosphorylation of JNK and paxillin (Ser178) at
      0.5h, indicating that endosome formation is required for initial signal
      enhancement. Further, depletion of PKCepsilon not only enhanced HGF-induced
      phosphorylation of JNK and paxillin (Ser178) but also prevented c-Met degradation
      at 0.5h, suggesting that PKCepsilon mediated c-Met degradation for signal
      declination. On the other hand, HGF induced colocalizations of both
      phosphorylated JNK and paxillin with the endosomal recycling protein GGA3 at 10h
      and depletion of GGA3 abolished membrane recycling of c-Met and phosphorylation
      of JNK/paxillin at the same time point. Interestingly, HGF induced GGA3
      phosphorylation in a PKCepsilon-dependent manner during 0.5-4h, which is
      associated with c-Met degradation in the same period. Finally, HGF-induced cell
      migration, invasion and intrahepatic metastasis of HepG2 were prevented by the
      inhibitors of endocytosis. Our results suggest that critical endosomal components
      are promising therapeutic targets for preventing HGF-induced progression of HCC. 

PMID- 25778905
TI  - Simulated evolution of fluorophores for light emitting diodes.
AB  - Organic light emitting diodes based on fluorophores with a propensity for
      thermally activated delayed fluorescence (TADF) are able to circumvent
      limitations imposed on device efficiency by spin statistics. Molecules with a
      propensity for TADF necessarily have two properties: a small gap between the
      lowest lying singlet and triplet excited states and a large transition dipole
      moment for fluorescence. In this work, we demonstrate the use of a genetic
      algorithm to search a region of chemical space for molecules with these
      properties. This algorithm is based on a flexible and intuitive representation of
      the molecule as a tree data structure, in which the nodes correspond to molecular
      fragments. Our implementation takes advantage of hybrid parallel graphics
      processing unit accelerated computer clusters to allow efficient sampling while
      retaining a reasonably accurate description of the electronic structure (in this
      case, CAM-B3LYP/6-31G(**)). In total, we have identified 3792 promising candidate
      fluorophores from a chemical space containing 1.26 * 10(6) molecules. This
      required performing electronic structure calculations on only 7518 molecules, a
      small fraction of the full space. Several novel classes of molecules which show
      promise as fluorophores are presented. 

PMID- 25778906
TI  - Robustness of a new molecular dynamics-finite element coupling approach for soft
      matter systems analyzed by uncertainty quantification.
AB  - Key parameters of a recently developed coarse-grained molecular dynamics-finite
      element coupling approach have been analyzed in the framework of uncertainty
      quantification (UQ). We have employed a polystyrene sample for the case study.
      The new hybrid approach contains several parameters which cannot be determined on
      the basis of simple physical arguments. Among others, this includes the so-called
      anchor points as information transmitters between the particle-based molecular
      dynamics (MD) domain and the surrounding finite element continuum, the force
      constant between polymer beads and anchor points, the number of anchor points,
      and the relative sizes of the MD core domain and the surrounding dissipative
      particle dynamics domain. Polymer properties such as density, radius of gyration,
      end-to-end distance, and radial distribution functions are calculated as a
      function of the above model parameters. The influence of these input parameters
      on the resulting polymer properties is studied by UQ. Our analysis shows that the
      hybrid method is highly robust. The variation of polymer properties of interest
      as a function of the input parameters is weak. 

PMID- 25778904
TI  - Small interfering RNA therapy against carbohydrate sulfotransferase 15 inhibits
      cardiac remodeling in rats with dilated cardiomyopathy.
AB  - Carbohydrate sulfotransferase 15 (CHST15) is a sulfotransferase responsible for
      biosynthesis of chondroitin sulfate E (CS-E), which plays important roles in
      numerous biological events such as biosynthesis of proinflammatory cytokines.
      However, the effects of CHST15 siRNA in rats with chronic heart failure (CHF)
      after experimental autoimmune myocarditis (EAM) have not yet been investigated.
      CHF was elicited in Lewis rats by immunization with cardiac myosin, and after
      immunization, the rats were divided into two groups and treated with either
      CHST15 siRNA (2MUg/week) or vehicle. Age matched normal rats without
      immunizations were also included in this study. After 7weeks of treatment, we
      investigated the effects of CHST15 siRNA on cardiac function, proinflammatory
      cytokines, and cardiac remodeling in EAM rats. Myocardial functional parameters
      measured by hemodynamic and echocardiographic studies were significantly improved
      by CHST15 siRNA treatment in rats with CHF compared with that of vehicle-treated
      CHF rats. CHST15 siRNA significantly reduced cardiac fibrosis, and hypertrophy
      and its marker molecules (left ventricular (LV) mRNA expressions of transforming
      growth factor beta1, collagens I and III, and atrial natriuretic peptide)
      compared with vehicle-treated CHF rats. CHF-induced increased myocardial mRNA
      expressions of proinflammatory cytokines [interleukin (IL)-6, IL-1beta], monocyte
      chemoattractant protein-1, and matrix metalloproteinases (MMP-2 and -9), and
      CHST15 were also suppressed by the treatment with CHST15 siRNA. Western blotting
      study has confirmed the results obtained from mRNA analysis as CHST15 siRNA
      treated rats expressed reduced levels of inflammatory and cardiac remodeling
      marker proteins. Our results demonstrate for the first time, that CHST15 siRNA
      treatment significantly improved LV function and ameliorated the progression of
      cardiac remodeling in rats with CHF after EAM. 

PMID- 25778907
TI  - The DYX2 locus and neurochemical signaling genes contribute to speech sound
      disorder and related neurocognitive domains.
AB  - A major milestone of child development is the acquisition and use of speech and
      language. Communication disorders, including speech sound disorder (SSD), can
      impair a child's academic, social and behavioral development. Speech sound
      disorder is a complex, polygenic trait with a substantial genetic component.
      However, specific genes that contribute to SSD remain largely unknown. To
      identify associated genes, we assessed the association of the DYX2 dyslexia risk
      locus and markers in neurochemical signaling genes (e.g., nicotinic and
      dopaminergic) with SSD and related endophenotypes. We first performed separate
      primary associations in two independent samples - Cleveland SSD (210 affected and
      257 unaffected individuals in 127 families) and Denver SSD (113 affected
      individuals and 106 unaffected individuals in 85 families) - and then combined
      results by meta-analysis. DYX2 markers, specifically those in the 3' untranslated
      region of DCDC2 (P = 1.43 * 10(-4) ), showed the strongest associations with
      phonological awareness. We also observed suggestive associations of dopaminergic
      related genes ANKK1 (P = 1.02 * 10(-2) ) and DRD2 (P = 9.22 * 10(-3) ) and
      nicotinic-related genes CHRNA3 (P = 2.51 * 10(-3) ) and BDNF (P = 8.14 * 10(-3) )
      with case-control status and articulation. Our results further implicate
      variation in putative regulatory regions in the DYX2 locus, particularly in
      DCDC2, influencing language and cognitive traits. The results also support
      previous studies implicating variation in dopaminergic and nicotinic neural
      signaling influencing human communication and cognitive development. Our findings
      expand the literature showing genetic factors (e.g., DYX2) contributing to
      multiple related, yet distinct neurocognitive domains (e.g., dyslexia, language
      impairment, and SSD). How these factors interactively yield different
      neurocognitive and language-related outcomes remains to be elucidated. 

PMID- 25778909
TI  - Multi level ecological fitting: indirect life cycles are not a barrier to host
      switching and invasion.
AB  - Many invasive species are able to escape from coevolved enemies and thus enjoy a
      competitive advantage over native species. However, during the invasion phase,
      non-native species must overcome many ecological and/or physiological hurdles
      before they become established and spread in their new habitats. This may explain
      why most introduced species either fail to establish or remain as rare
      interstitials in their new ranges. Studies focusing on invasive species have been
      based on plants or animals where establishment requires the possession of
      preadapted traits from their native ranges that enables them to establish and
      spread in their new habitats. The possession of preadapted traits that facilitate
      the exploitation of novel resources or to colonize novel habitats is known as
      'ecological fitting'. Some species have evolved traits and life histories that
      reflect highly intimate associations with very specific types of habitats or
      niches. For these species, their phenological windows are narrow, and thus the
      ability to colonize non-native habitats requires that a number of conditions need
      to be met in accordance with their more specialized life histories. Some of the
      strongest examples of more complex ecological fitting involve invasive parasites
      that require different animal hosts to complete their life cycles. For instance,
      the giant liver fluke, Fascioloides magna, is a major parasite of several species
      of ungulates in North America. The species exhibits a life cycle whereby newly
      hatched larvae must find suitable intermediate hosts (freshwater snails) and
      mature larvae, definitive hosts (ungulates). Intermediate and definitive host
      ranges of F. magna in its native range are low in number, yet this parasite has
      been successfully introduced into Europe where it has become a parasite of native
      European snails and deer. We discuss how the ability of these parasites to
      overcome multiple ecophysiological barriers represents an excellent example of
      'multiple-level ecological fitting'. 

PMID- 25778908
TI  - Forms of non-suicidal self-injury as a function of trait aggression.
AB  - To date, the considerable body of research on predictors of non-suicidal self
      injury (NSSI) has conceptualized NSSI as a unitary construct despite the fact
      that NSSI can exist in many forms (e.g., hitting, cutting, burning). The goal of
      the present study is to examine differential prediction of forms of NSSI.
      Specifically, we examined trait aggression as a predictor of more aggressive
      forms of NSSI (i.e., hitting). We hypothesized that higher trait aggression would
      differentiate those who engaged in hitting forms of NSSI from those who did not,
      whereas other factors (i.e., emotion regulation and trait anger) would serve as a
      non-specific predictor of NSSI. We also hypothesized that higher trait aggression
      would be related to lifetime frequency of hitting NSSI, but not other forms of
      NSSI, whereas emotion regulation and anger would act as predictors of other forms
      of NSSI. To test these hypotheses, a large sample of young adults completed
      measures of trait aggression, trait anger, emotion regulation, and NSSI
      behaviors. Results were generally in line with our hypotheses. Higher levels of
      trait aggression differentiated those who engaged in hitting NSSI from those who
      did not and was also associated with greater frequency of hitting NSSI. These
      results imply that different factors predict different forms of NSSI and that
      NSSI may be best examined as a multi-faceted construct. 

PMID- 25778910
TI  - Meta-analyses: what is heterogeneity?

PMID- 25778911
TI  - Requirement of CHROMOMETHYLASE3 for somatic inheritance of the spontaneous tomato
      epimutation Colourless non-ripening.
AB  - Naturally-occurring epimutants are rare and have mainly been described in plants.
      However how these mutants maintain their epigenetic marks and how they are
      inherited remain unknown. Here we report that CHROMOMETHYLASE3 (SlCMT3) and other
      methyltransferases are required for maintenance of a spontaneous epimutation and
      its cognate Colourless non-ripening (Cnr) phenotype in tomato. We screened a
      series of DNA methylation-related genes that could rescue the hypermethylated Cnr
      mutant. Silencing of the developmentally-regulated SlCMT3 gene results in
      increased expression of LeSPL-CNR, the gene encodes the SBP-box transcription
      factor residing at the Cnr locus and triggers Cnr fruits to ripen normally.
      Expression of other key ripening-genes was also up-regulated. Targeted and whole
      genome bisulfite sequencing showed that the induced ripening of Cnr fruits is
      associated with reduction of methylation at CHG sites in a 286-bp region of the
      LeSPL-CNR promoter, and a decrease of DNA methylation in differentially
      methylated regions associated with the LeMADS-RIN binding sites. Our results
      indicate that there is likely a concerted effect of different methyltransferases
      at the Cnr locus and the plant-specific SlCMT3 is essential for sustaining Cnr
      epi-allele. Maintenance of DNA methylation dynamics is critical for the somatic
      stability of Cnr epimutation and for the inheritance of tomato non-ripening
      phenotype. 

PMID- 25778912
TI  - IL-12/15/18-preactivated NK cells suppress GvHD in a mouse model of mismatched
      hematopoietic cell transplantation.
AB  - Mismatched hematopoietic cell transplants for treating leukemia are complicated
      by graft versus host disease (GvHD). Here, we show that adoptively transferred IL
      12/15/18-preactivated NK cells suppress GvHD in a mouse model of fully mismatched
      hematopoietic cell transplantation. These IL-12/15/18-preactivated NK cells
      maintained Eomesodermin (Eomes) and T-bet expression upon transfer and, while
      there was no evidence of direct killing of donor T cells or host DCs by the IL
      12/15/18-preactivated NK cells, proliferation of donor T cells was inhibited.
      Strikingly, the graft versus leukemia effect mediated by donor T cells was
      retained, resulting in improved overall survival of mice that received lymphoma
      cells, donor allogeneic T cells, and IL-12/15/18-preactivated NK cells. These
      results suggest that IL-12/15/18-preactivated NK cells may be useful in improving
      immunotherapy of mismatched hematopoietic cell transplantation. Compared with
      previously proposed protocols, our findings suggest that in vitro NK-cell
      preactivation with this cytokine cocktail offers the significant advantage that
      cytokines do not need to be administered systemically to sustain NK-cell
      activity, thus avoiding toxicity. 

PMID- 25778914
TI  - Johanna Ivaska: Finding opposing forces in integrins.

PMID- 25778913
TI  - A nucleosome turnover map reveals that the stability of histone H4 Lys20
      methylation depends on histone recycling in transcribed chromatin.
AB  - Nucleosome composition actively contributes to chromatin structure and
      accessibility. Cells have developed mechanisms to remove or recycle histones,
      generating a landscape of differentially aged nucleosomes. This study aimed to
      create a high-resolution, genome-wide map of nucleosome turnover in
      Schizosaccharomyces pombe. The recombination-induced tag exchange (RITE) method
      was used to study replication-independent nucleosome turnover through the
      appearance of new histone H3 and the disappearance or preservation of old histone
      H3. The genome-wide location of histones was determined by chromatin
      immunoprecipitation-exonuclease methodology (ChIP-exo). The findings were
      compared with diverse chromatin marks, including histone variant H2A.Z, post
      translational histone modifications, and Pol II binding. Finally, genome-wide
      mapping of the methylation states of H4K20 was performed to determine the
      relationship between methylation (mono, di, and tri) of this residue and
      nucleosome turnover. Our analysis showed that histone recycling resulted in low
      nucleosome turnover in the coding regions of active genes, stably expressed at
      intermediate levels. High levels of transcription resulted in the incorporation
      of new histones primarily at the end of transcribed units. H4K20 was methylated
      in low-turnover nucleosomes in euchromatic regions, notably in the coding regions
      of long genes that were expressed at low levels. This transcription-dependent
      accumulation of histone methylation was dependent on the histone chaperone
      complex FACT. Our data showed that nucleosome turnover is highly dynamic in the
      genome and that several mechanisms are at play to either maintain or suppress
      stability. In particular, we found that FACT-associated transcription conserves
      histones by recycling them and is required for progressive H4K20 methylation. 

PMID- 25778915
TI  - A short guide to technology development in cell biology.
AB  - New technologies drive progress in many research fields, including cell biology.
      Much of technological innovation comes from "bottom-up" efforts by individual
      students and postdocs. However, technology development can be challenging, and a
      successful outcome depends on many factors. This article outlines some
      considerations that are important when embarking on a technology development
      project. Despite the challenges, developing a new technology can be extremely
      rewarding and could lead to a lasting impact in a given field. 

PMID- 25778916
TI  - Balancing cell behavior at boundaries.
AB  - The restriction of cell intermingling across boundaries is essential for the
      establishment of discrete tissues. Eph receptor signaling prevents intermingling
      at many boundaries. In this issue, Luu et al. (2015. J. Cell Biol.
      http://dx.doi.org/10.1083/jcb.201409026) report a parallel pathway, mediated by
      Wnt signaling, Snail1, and paraxial protocadherin (PAPC). This pathway
      establishes a distinctive organization of cell adhesion and intercellular gaps at
      the interface between tissues. 

PMID- 25778917
TI  - The nucleoporin gp210/Nup210 controls muscle differentiation by regulating
      nuclear envelope/ER homeostasis.
AB  - Previously, we identified the nucleoporin gp210/Nup210 as a critical regulator of
      muscle and neuronal differentiation, but how this nucleoporin exerts its function
      and whether it modulates nuclear pore complex (NPC) activity remain unknown.
      Here, we show that gp210/Nup210 mediates muscle cell differentiation in vitro via
      its conserved N-terminal domain that extends into the perinuclear space. Removal
      of the C-terminal domain, which partially mislocalizes gp210/Nup210 away from
      NPCs, efficiently rescues the differentiation defect caused by the knockdown of
      endogenous gp210/Nup210. Unexpectedly, a gp210/Nup210 mutant lacking the NPC
      targeting transmembrane and C-terminal domains is sufficient for C2C12 myoblast
      differentiation. We demonstrate that the endoplasmic reticulum (ER) stress
      specific caspase cascade is exacerbated during Nup210 depletion and that blocking
      ER stress-mediated apoptosis rescues differentiation of Nup210-deficient cells.
      Our results suggest that the role of gp210/Nup210 in cell differentiation is
      mediated by its large luminal domain, which can act independently of NPC
      association and appears to play a pivotal role in the maintenance of nuclear
      envelope/ER homeostasis. 

PMID- 25778918
TI  - Somatic CRISPR-Cas9-induced mutations reveal roles of embryonically essential
      dynein chains in Caenorhabditis elegans cilia.
AB  - Cilium formation and maintenance require intraflagellar transport (IFT). Although
      much is known about kinesin-2-driven anterograde IFT, the composition and
      regulation of retrograde IFT-specific dynein remain elusive. Components of
      cytoplasmic dynein may participate in IFT; however, their essential roles in cell
      division preclude functional studies in postmitotic cilia. Here, we report that
      inducible expression of the clustered regularly interspaced short palindromic
      repeats (CRISPR)-Cas9 system in Caenorhabditis elegans generated conditional
      mutations in IFT motors and particles, recapitulating ciliary defects in their
      null mutants. Using this method to bypass the embryonic requirement, we show the
      following: the dynein intermediate chain, light chain LC8, and lissencephaly-1
      regulate retrograde IFT; the dynein light intermediate chain functions in
      dendrites and indirectly contributes to ciliogenesis; and the Tctex and Roadblock
      light chains are dispensable for cilium assembly. Furthermore, we demonstrate
      that these components undergo biphasic IFT with distinct transport frequencies
      and turnaround behaviors. Together, our results suggest that IFT-dynein and
      cytoplasmic dynein have unique compositions but also share components and
      regulatory mechanisms. 

PMID- 25778919
TI  - Aurora B prevents chromosome arm separation defects by promoting telomere
      dispersion and disjunction.
AB  - The segregation of centromeres and telomeres at mitosis is coordinated at
      multiple levels to prevent the formation of aneuploid cells, a phenotype
      frequently observed in cancer. Mitotic instability arises from chromosome
      segregation defects, giving rise to chromatin bridges at anaphase. Most of these
      defects are corrected before anaphase onset by a mechanism involving Aurora B
      kinase, a key regulator of mitosis in a wide range of organisms. Here, we
      describe a new role for Aurora B in telomere dispersion and disjunction during
      fission yeast mitosis. Telomere dispersion initiates in metaphase, whereas
      disjunction takes place in anaphase. Dispersion is promoted by the dissociation
      of Swi6/HP1 and cohesin Rad21 from telomeres, whereas disjunction occurs at
      anaphase after the phosphorylation of condensin subunit Cnd2. Strikingly, we
      demonstrate that deletion of Ccq1, a telomeric shelterin component, rescued cell
      death after Aurora inhibition by promoting the loading of condensin on chromosome
      arms. Our findings reveal an essential role for telomeres in chromosome arm
      segregation. 

PMID- 25778920
TI  - Altering nuclear pore complex function impacts longevity and mitochondrial
      function in S. cerevisiae.
AB  - The eukaryotic nuclear permeability barrier and selective nucleocytoplasmic
      transport are maintained by nuclear pore complexes (NPCs), large structures
      composed of ~ 30 proteins (nucleoporins [Nups]). NPC structure and function are
      disrupted in aged nondividing metazoan cells, although it is unclear whether
      these changes are a cause or consequence of aging. Using the replicative life
      span (RLS) of Saccharomyces cerevisiae as a model, we find that specific Nups and
      transport events regulate longevity independent of changes in NPC permeability.
      Mutants lacking the GLFG domain of Nup116 displayed decreased RLSs, whereas
      longevity was increased in nup100-null mutants. We show that Nup116 mediates
      nuclear import of the karyopherin Kap121, and each protein is required for
      mitochondrial function. Both Kap121-dependent transport and Nup116 levels
      decrease in replicatively aged yeast. Overexpression of GSP1, the small GTPase
      that powers karyopherin-mediated transport, rescued mitochondrial and RLS defects
      in nup116 mutants and increased longevity in wild-type cells. Together, these
      studies reveal that specific NPC nuclear transport events directly influence
      aging.

PMID- 25778921
TI  - Hrr25/CK1delta-directed release of Ltv1 from pre-40S ribosomes is necessary for
      ribosome assembly and cell growth.
AB  - Casein kinase 1delta/epsilon (CK1delta/epsilon) and their yeast homologue Hrr25
      are essential for cell growth. Further, CK1delta is overexpressed in several
      malignancies, and CK1delta inhibitors have shown promise in several preclinical
      animal studies. However, the substrates of Hrr25 and CK1delta/epsilon that are
      necessary for cell growth and survival are unknown. We show that Hrr25 is
      essential for ribosome assembly, where it phosphorylates the assembly factor
      Ltv1, which causes its release from nascent 40S subunits and allows subunit
      maturation. Hrr25 inactivation or expression of a nonphosphorylatable Ltv1
      variant blocked Ltv1 release in vitro and in vivo, and prevented entry into the
      translation-like quality control cycle. Conversely, phosphomimetic Ltv1 variants
      rescued viability after Hrr25 depletion. Finally, Ltv1 knockdown in human breast
      cancer cells impaired apoptosis induced by CK1delta/epsilon inhibitors,
      establishing that the antiproliferative activity of these inhibitors is due, at
      least in part, to disruption of ribosome assembly. These findings validate the
      ribosome assembly pathway as a novel target for the development of anticancer
      therapeutics. 

PMID- 25778922
TI  - NORE1A is a Ras senescence effector that controls the apoptotic/senescent balance
      of p53 via HIPK2.
AB  - The Ras oncoprotein is a key driver of cancer. However, Ras also provokes
      senescence, which serves as a major barrier to Ras-driven transformation. Ras
      senescence pathways remain poorly characterized. NORE1A is a novel Ras effector
      that serves as a tumor suppressor. It is frequently inactivated in tumors. We
      show that NORE1A is a powerful Ras senescence effector and that down-regulation
      of NORE1A suppresses senescence induction by Ras and enhances Ras transformation.
      We show that Ras induces the formation of a complex between NORE1A and the kinase
      HIPK2, enhancing HIPK2 association with p53. HIPK2 is a tumor suppressor that can
      induce either proapoptotic or prosenescent posttranslational modifications of
      p53. NORE1A acts to suppress its proapoptotic phosphorylation of p53 but enhance
      its prosenescent acetylation of p53. Thus, we identify a major new Ras signaling
      pathway that links Ras to the control of specific protein acetylation and show
      how NORE1A allows Ras to qualitatively modify p53 function to promote senescence.

PMID- 25778924
TI  - BRCA2 diffuses as oligomeric clusters with RAD51 and changes mobility after DNA
      damage in live cells.

PMID- 25778923
TI  - PAPC mediates self/non-self-distinction during Snail1-dependent tissue
      separation.
AB  - Cleft-like boundaries represent a type of cell sorting boundary characterized by
      the presence of a physical gap between tissues. We studied the cleft-like
      ectoderm-mesoderm boundary in Xenopus laevis and zebrafish gastrulae. We
      identified the transcription factor Snail1 as being essential for tissue
      separation, showed that its expression in the mesoderm depends on noncanonical
      Wnt signaling, and demonstrated that it enables paraxial protocadherin (PAPC) to
      promote tissue separation through two novel functions. First, PAPC attenuates
      planar cell polarity signaling at the ectoderm-mesoderm boundary to lower cell
      adhesion and facilitate cleft formation. Second, PAPC controls formation of a
      distinct type of adhesive contact between mesoderm and ectoderm cells that shows
      properties of a cleft-like boundary at the single-cell level. It consists of
      short stretches of adherens junction-like contacts inserted between intermediate
      sized contacts and large intercellular gaps. These roles of PAPC constitute a
      self/non-self-recognition mechanism that determines the site of boundary
      formation at the interface between PAPC-expressing and -nonexpressing cells. 

PMID- 25778925
TI  - Molecular binding behavior of bipyridium derivatives by water-soluble carboxylato
      biphen[3]arene.
AB  - Complexation of two types of dicationic bipyridium guests, paraquat derivatives
      and bis(N-mono-substituted bipyridine) cations, by a negatively charged
      carboxylato-biphen[3]arene (CBP3) in water is reported. CBP3 could strongly
      interact with these guests, where charge-transfer and electrostatic interactions
      play important roles. 

PMID- 25778926
TI  - Management of advanced intracranial intradural juvenile nasopharyngeal
      angiofibroma: combined single-stage rhinosurgical and neurosurgical approach.
AB  - BACKGROUND: Although intracranial extension of juvenile nasopharyngeal
      angiofibroma (JNA) occurs commonly, intradural penetration is extremely rare.
      Management of such tumors is a challenging issue in skull-base surgery,
      necessitating their removal via combined approaches. In this work, we share our
      experience in management of extensive intradural JNA. METHODS: In a university
      hospital-based setting of 2 tertiary care academic centers, retrospective chart
      of 6 male patients (5 between 15 and 19 years old) was reviewed. Patients
      presented chiefly with nasal obstruction, epistaxis, and proptosis. One of them
      was an aggressive recurrent tumor in a 32-year-old patient. All cases underwent
      combined transnasal, transmaxillary, and craniotomy approaches assisted by the
      use of image-guided endoscopic surgery, with craniotomy preceding the
      rhinosurgical approach in 3 cases. RESULTS: Adding a transcranial approach to the
      transnasal and transmaxillary endoscopic approaches provided 2-sided exposure and
      appreciated access to the huge intradural JNAs. One postoperative cerebrospinal
      fluid leak and 1 postoperative recurrence at the site of infratemporal fossa were
      treated successfully. Otherwise, the course was uneventful in the remaining
      cases. CONCLUSION: Management of intracranial intradural JNA requires a
      multidisciplinary approach of combined open and endoscopic-assisted rhinosurgery
      and neurosurgery, because of greater risk for complications during the
      dissection. Carotid rupture and brain damage remain 2 catastrophic complications
      that should always be kept in mind. A combined rhinosurgical and neurosurgical
      approach also has the advantage of very modest cosmetic complications.

PMID- 25778927
TI  - Characterization of cyclic peptides containing disulfide bonds.
AB  - Unlike linear peptides, analysis of cyclic peptides containing disulfide bonds is
      not straightforward and demands indirect methods to achieve a rigorous proof of
      structure. Three peptides that belong to this category, p-Cl-Phe-DPDPE, DPDPE,
      and CTOP, were analyzed and the results are presented in this paper. The great
      potential of two dimensional NMR and ESI tandem mass spectrometry was harnessed
      during the course of peptide characterizations. A new RP-HPLC method for the
      analysis of trifluoroacetic acid is also presented. It is robust, simple, and
      efficient compared to the currently available methods. 

PMID- 25778928
TI  - Simultaneous quantification of three active alkaloids from a traditional Chinese
      medicine Ramulus Mori (Sangzhi) in rat plasma using liquid chromatography-tandem
      mass spectrometry.
AB  - Fagomine, 1-deoxynojirimycin (DNJ) and 1,4-dideoxy-1,4-imino-d-arabinitol (DAB)
      are the major bioactive constituents in the active fraction of alkaloids from the
      traditional Chinese medicine mulberry twig (Ramulus Mori, Chinese name Sang Zhi),
      which has a strong activity on alpha-glucosidase in vitro and in vivo. A rapid
      and sensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS) method
      was developed and validated for the simultaneous determination of DNJ, fagomine
      and DAB in rat plasma. Plasma samples were prepared using a simple protein
      precipitation by the addition of 1% volume of Tris and two volumes of methanol
      acetonitrile. The analytes and internal standard (IS, miglitol) were
      chromatographed in an XBridgeTM amide column with a gradient mobile phase of
      acetonitrile-water (0.1% ammonium hydroxide) at a flow rate of 0.7mL/min. The
      detection was performed on a triple quadrupole tandem mass spectrometer equipped
      with electrospray ionization (ESI) source in positive ion mode by multiple
      reaction monitoring (MRM) mode. Linear detection responses were obtained for DNJ
      ranging from 5.00 to 5000.00ng/mL, 10.00 to 2500.00ng/mL for fagomine and DAB.
      The lower limits of quantification (LLOQs) were 5.00, 10.00, 10.00ng/mL for DNJ,
      fagomine and DAB, respectively. Intra-day and inter-day precisions (R.S.D.%) were
      within 10% for three analytes with accuracies (R.E.%) less than 12%. The mean
      recoveries of analytes were greater than 85%. All analytes were proved to be
      stable during the sample storage, preparation and analytic procedures. The method
      was successfully applied to the pharmacokinetic study of the three alkaloids in
      rats after oral administration of the active fraction of alkaloids from mulberry
      twig.

PMID- 25778929
TI  - An integrated high resolution mass spectrometric data acquisition method for
      rapid screening of saponins in Panax notoginseng (Sanqi).
AB  - The aim of this study was to develop a convenient method without pretreatments
      for nontarget discovery of interested compounds. The segment and exposure
      strategy, coupled with two mass spectrometer data acquisition methods was firstly
      proposed for screening the saponins in extract of Panax notoginseng (Sanqi) via
      high-performance liquid chromatography tandem quadrupole time-of-flight mass
      spectrometry (HPLC-QTOF/MS). By gradually removing certain major or moderate
      interference compounds, the developed segment and exposure strategy could
      significantly improve the detection efficiency for trace compounds. Moreover, the
      newly developed five-point screening approach based on a modified mass defect
      filter strategy and the visual isotopic ion technique was verified to be
      efficient and reliable in picking out the interested precursor ions. In total,
      234 ginsenosides including 67 potential new ones were characterized or
      tentatively identified from the extract of Sanqi. Particularly, some unusual
      compounds containing the branched glycosyl group or new substituted acyl groups
      were firstly reported. The proposed integrated strategy held a strong promise for
      analyses of the complex mixtures.

PMID- 25778930
TI  - A new and fast DLLME-CE method for the enantioselective analysis of zopiclone and
      its active metabolite after fungal biotransformation.
AB  - Zopiclone (ZO) is a chiral drug that undergoes extensive metabolism to N
      desmethylzopiclone (N-Des-ZO) and zopiclone-N-oxide (N-Ox-ZO). Pharmacological
      studies have shown (S)-N-Des-ZO metabolite presents anxiolytic activity and a
      patent for this metabolite was requested for anxiety treatment and related
      disorders. In this context, biotransformation employing fungi may be a promising
      strategy to obtain N-Des-ZO. To perform the biotransformation study in this work,
      an enantioselective method based on capillary electrophoresis (CE) and dispersive
      liquid-liquid microextraction (DLLME) was developed. CE analyses were carried out
      in sodium phosphate buffer (pH 2.5; 50mmolL(-1)) containing 0.5% (w/v)
      carboxymethyl-beta-CD, at a constant voltage of +25kV. DLLME was conducted using
      2mL of liquid culture medium pH 9.5. Chloroform (100MUL) and methanol (300MUL)
      were employed as extraction and disperser solvent, respectively. After CE and
      DLLME optimization, the analytical method was fully validated. The method was
      linear over a concentration range of 90-6000ngmL(-1) for each ZO enantiomer
      (r>0.999) and 50-1000ngmL(-1) for each N-Des-ZO enantiomer (r>0.998). Absolute
      recovery of 51 and 82% was achieved for N-Des-ZO and ZO, respectively. The
      accuracy and precision results agreed with the EMA (European Medicines Agency)
      guideline, and so did the stability study. Application of the developed method in
      a biotransformation study was conducted in order to investigate the ability of
      fungi, belonging to the genus Cunninghamella, in metabolizing ZO chiral drug.
      Fungi Cunninghamella elegans ATCC 10028B and Cunninghamella echinulata var
      elegans ATCC 8688A demonstrated to be able to enantioselectively biotransform ZO
      to its active metabolite, N-Des-ZO. Therefore, the proposed goals of this work,
      i.e. a fast DLLME-CE method and an outstanding strategy to obtain N-Des-ZO, were
      successfully attained.

PMID- 25778931
TI  - Validation of the STRATIFY falls risk-assessment tool for acute-care hospital
      patients and nursing home residents: study protocol.
AB  - AIM: To evaluate the accuracy of the STRATIFY tool in detecting and predicting
      fall risk in acute-care hospitals and nursing homes for the older people.
      BACKGROUND: Falls are the predominant cause of injury in people aged over 65
      years. Testing the falls risk-assessment tools in settings other than those for
      which they were originally developed obtained conflicting results and has
      highlighted difficulties in their adoption for widespread use. Current guidelines
      for practice call into question the appropriateness of using these instruments.
      DESIGN: Two-stage study: a cross-cultural adaptation and psychometric validation;
      and a longitudinal, prospective follow-up of the cohort of patients recruited.
      METHODS: A cross-cultural adaptation of STRATIFY, followed by its empirical
      validation will be performed, on a total sample of 2097 patients. The diagnostic
      validity will be assessed by calculating the sensitivity, specificity, positive
      and negative predictive values and the ratios of positive and negative
      probability. Data for statistical reliability and the internal consistency of the
      instrument will be calculated; construct validity will be assessed by factor
      analysis and criterion validity determined according to the Downton index. The
      incidence and the hazard ratio of falls will be analysed for the study factors
      included. Funding of the review was confirmed in December 2013. DISCUSSION: The
      rigorous assessment of STRATIFY using large samples, in populations with
      different levels of risk and implementing a longitudinal follow-up to determine
      the effect of revaluation on the incidence of falls, will give stronger evidence
      for the establishment of future recommendations in Clinical Practice Guidelines.

PMID- 25778932
TI  - Sodium valproate, a histone deacetylase inhibitor, modulates the vascular
      endothelial growth inhibitor-mediated cell death in human osteosarcoma and
      vascular endothelial cells.
AB  - The level of vascular endothelial growth inhibitor (VEGI) has been reported to be
      negatively associated with neovascularization in malignant tumors. The soluble
      form of VEGI is a potent anti-angiogenic factor due to its effects in inhibiting
      endothelial cell proliferation. This inhibition is mediated by death receptor 3
      (DR3), which contains a death domain in its cytoplasmic tail capable of inducing
      apoptosis that can be subsequently blocked by decoy receptor 3 (DcR3). We
      investigated the effects of sodium valproate (VPA) and trichostatin A (TSA),
      histone deacetylase inhibitors, on the expression of VEGI and its related
      receptors in human osteosarcoma (OS) cell lines and human microvascular
      endothelial (HMVE) cells. Consequently, treatment with VPA and TSA increased the
      VEGI and DR3 expression levels without inducing DcR3 production in the OS cell
      lines. In contrast, the effect on the HMVE cells was limited, with no evidence of
      growth inhibition or an increase in the DR3 and DcR3 expression. However, VPA
      induced soluble VEGI in the OS cell culture medium markedly inhibited the
      vascular tube formation of HMVE cells, while VEGI overexpression resulted in
      enhanced OS cell death. Taken together, the HDAC inhibitor has anti-angiogenesis
      and antitumor activities that mediate soluble VEGI/DR3-induced apoptosis via both
      autocrine and paracrine pathways. This study indicates that the HDAC inhibitor
      may be exploited as a therapeutic strategy modulating the soluble VEGI/DR3
      pathway in osteosarcoma patients.

PMID- 25778933
TI  - Combination paracetamol and ibuprofen for pain relief after oral surgery: a dose
      ranging study.
AB  - PURPOSE: Combined paracetamol and ibuprofen has been shown to be more effective
      than either constituent alone for acute pain in adults, but the dose-response has
      not been confirmed. The aim of this study was to define the analgesic dose
      response relationship of different potential doses of a fixed dose combination
      containing paracetamol and ibuprofen after third molar surgery. METHODS: Patients
      aged 16 to 60 years with moderate or severe pain after the removal of at least
      two impacted third molars were randomised to receive double-blind study
      medication as two tablets every 6 h for 24 h of either of the following: two
      tablet, combination full dose (paracetamol 1000 mg and ibuprofen 300 mg); one
      tablet, combination half dose (paracetamol 500 mg and ibuprofen 150 mg); half a
      tablet, combination quarter dose (paracetamol 250 mg and ibuprofen 75 mg); or
      placebo. The primary outcome measure was the time-adjusted summed pain intensity
      difference over 24 h (SPID 24) calculated from the 100-mm VAS assessments
      collected over multiple time points for the study duration. RESULTS: Data from
      159 patients were included in the analysis. Mean (SD) time-adjusted SPID over 24
      h were full-dose combination 20.1 (18.0), half dose combination 20.4 (20.8),
      quarter dose combination 19.3 (20.0) and placebo 6.6 (19.8). There was a
      significant overall effect of dose (p = 0.002) on the primary outcome. Planned
      pairwise comparisons showed that all combination dose groups were superior to
      placebo (full dose vs. placebo p = 0.004, half dose vs. placebo p = 0.002,
      quarter dose vs. placebo p = 0.002). The overall effect of dose was also
      significant for maximum VAS pain intensity score (p = 0.048), response rate (p =
      0.0094), percentage of participants requiring rescue (p = 0.025) and amount of
      rescue (p < 0.001). No significant dose effect was found for time to peak
      reduction in VAS or time to meaningful pain relief. The majority of adverse
      events recorded were of mild (52.75%) or moderate (40.16%) severity and not
      related (30.7%) or unlikely related (57.5%) to the study medication. CONCLUSION:
      All doses of the combination provide safe superior pain relief to placebo in
      adult patients following third molar removal surgery.

PMID- 25778934
TI  - Prolonged inductive effect of rifampicin on linezolid exposure.

PMID- 25778935
TI  - Twenty-five years of confirmatory adaptive designs: opportunities and pitfalls.
AB  - 'Multistage testing with adaptive designs' was the title of an article by Peter
      Bauer that appeared 1989 in the German journal Biometrie und Informatik in
      Medizin und Biologie. The journal does not exist anymore but the methodology
      found widespread interest in the scientific community over the past 25 years. The
      use of such multistage adaptive designs raised many controversial discussions
      from the beginning on, especially after the publication by Bauer and Kohne 1994
      in Biometrics: Broad enthusiasm about potential applications of such designs
      faced critical positions regarding their statistical efficiency. Despite, or
      possibly because of, this controversy, the methodology and its areas of
      applications grew steadily over the years, with significant contributions from
      statisticians working in academia, industry and agencies around the world. In the
      meantime, such type of adaptive designs have become the subject of two major
      regulatory guidance documents in the US and Europe and the field is still
      evolving. Developments are particularly noteworthy in the most important
      applications of adaptive designs, including sample size reassessment, treatment
      selection procedures, and population enrichment designs. In this article, we
      summarize the developments over the past 25 years from different perspectives. We
      provide a historical overview of the early days, review the key methodological
      concepts and summarize regulatory and industry perspectives on such designs.
      Then, we illustrate the application of adaptive designs with three case studies,
      including unblinded sample size reassessment, adaptive treatment selection, and
      adaptive endpoint selection. We also discuss the availability of software for
      evaluating and performing such designs. We conclude with a critical review of how
      expectations from the beginning were fulfilled, and - if not - discuss potential
      reasons why this did not happen.

PMID- 25778936
TI  - Autoantigen BiP-Derived HLA-DR4 Epitopes Differentially Recognized by Effector
      and Regulatory T Cells in Rheumatoid Arthritis.
AB  - OBJECTIVE: The balance between effector and regulatory CD4+ T cells plays a key
      role in the pathogenesis of rheumatoid arthritis (RA). The aim of this study was
      to examine whether the RA autoantigen BiP has epitopes for both effector and
      regulatory immunities. METHODS: The proliferation and cytokine secretion of
      peripheral blood mononuclear cells (PBMCs) from HLA-DR4-positive RA patients in
      response to BiP-derived peptides were examined by (3)H-thymidine uptake and
      enzyme-linked immunosorbent assay. As a mouse therapeutic model, a BiP-derived
      peptide was administered orally to mice with collagen-induced arthritis (CIA).
      RESULTS: Among the peptides examined, BiP(336-355) induced the strongest
      proliferation of PBMCs from RA patients, but not from healthy donors. The
      proliferation of PBMCs in response to BiP(336-355) showed a correlation with
      clinical RA activity and serum anti-BiP/citrullinated BiP antibodies. In
      contrast, BiP(456-475) induced interleukin-10 (IL-10) secretion from CD25
      positive PBMCs obtained from RA patients and healthy donors without inducing cell
      proliferation, and it actively suppressed the BiP(336-355)-induced proliferation
      and proinflammatory cytokine secretion by PBMCs. Oral administration of BiP(456
      475) to mice with CIA reduced the severity of arthritis and T cell proliferation
      and increased the secretion of IL-10 from T cells as well as the number of
      CD4+CD25+FoxP3+ regulatory T cells. CONCLUSION: Effector and regulatory T cells
      recognized different BiP epitopes. The deviated balance toward BiP-specific
      effector T cells in RA may be associated with disease activity; therefore, BiP
      specific effector or regulatory T cells could be a target of new RA therapies.

PMID- 25778937
TI  - Pneumococcal carriage in rural Gambia prior to the introduction of pneumococcal
      conjugate vaccine: a population-based survey.
AB  - OBJECTIVE: To evaluate pneumococcal colonisation before and after the
      introduction of pneumococcal conjugate vaccine (PCV) in eastern Gambia. METHODS:
      Population-based cross-sectional survey of pneumococcal carriage between May and
      August 2009 before the introduction of PCV into the Expanded Program on
      Immunization. Nasopharyngeal swabs were collected from all household members, but
      in selected households, only children aged 6-10 years were swabbed. This age
      group participated in an earlier trial of a nine-valent PCV between 2000 and
      2004. RESULTS: The prevalence of nasopharyngeal pneumococcal carriage in 2933
      individuals was 72.0% in underfives (N = 515), 41.6% in children aged 5-17 (N =
      1508) and 13.0% in adults >=18 (N = 910) years. The age-specific prevalence of
      serotypes included in PCV7, PCV10 and PCV13 was 24.7%, 26.6% and 46.8% among
      children <5 years of age; 8.5%, 9.2% and 17.7% among children 5-17 years; and
      2.5%, 3.3% and 5.5% among adults >=18 years. The most common serotypes were 6A
      (13.1%), 23F (7.6%), 3 (7.3%), 19F (7.1%) and 34 (4.6%). There was no difference
      in the overall carriage of pneumococci between vaccinated and unvaccinated
      children 8 years after the primary vaccination with three doses of PCV (48.3% vs.
      41.1%). CONCLUSION: Before the introduction of PCV, serotypes included in PCV13
      accounted for about half the pneumococcal serotypes in nasopharyngeal carriage.
      Thus, the potential impact of PCV13 on pneumococcal disease in the Gambia is
      substantial.

PMID- 25778938
TI  - Unstable argininosuccinate lyase in variant forms of the urea cycle disorder
      argininosuccinic aciduria.
AB  - Loss of function of the urea cycle enzyme argininosuccinate lyase (ASL) is caused
      by mutations in the ASL gene leading to ASL deficiency (ASLD). ASLD has a broad
      clinical spectrum ranging from life-threatening severe neonatal to asymptomatic
      forms. Different levels of residual ASL activity probably contribute to the
      phenotypic variability but reliable expression systems allowing clinically useful
      conclusions are not yet available. In order to define the molecular
      characteristics underlying the phenotypic variability, we investigated all ASL
      mutations that were hitherto identified in patients with late onset or mild
      clinical and biochemical courses by ASL expression in human embryonic kidney 293
      T cells. We found residual activities >3% of ASL wild type (WT) in nine of 11 ASL
      mutations. Six ASL mutations (p.Arg95Cys, p.Ile100Thr, p.Val178Met, p.Glu189Gly,
      p.Val335Leu, and p.Arg379Cys) with residual activities >=16% of ASL WT showed no
      significant or less than twofold reduced Km values, but displayed thermal
      instability. Computational structural analysis supported the biochemical findings
      by revealing multiple effects including protein instability, disruption of ionic
      interactions and hydrogen bonds between residues in the monomeric form of the
      protein, and disruption of contacts between adjacent monomeric units in the ASL
      tetramer. These findings suggest that the clinical and biochemical course in
      variant forms of ASLD is associated with relevant residual levels of ASL activity
      as well as instability of mutant ASL proteins. Since about 30% of known ASLD
      genotypes are affected by mutations studied here, ASLD should be considered as a
      candidate for chaperone treatment to improve mutant protein stability.

PMID- 25778939
TI  - Acute rhabdomyolysis and inflammation.
AB  - Rhabdomyolysis results from the rapid breakdown of skeletal muscle fibers, which
      leads to leakage of potentially toxic cellular content into the systemic
      circulation. Acquired causes by direct injury to the sarcolemma are most
      frequent. The inherited causes are: i) metabolic with failure of energy
      production, including mitochondrial fatty acid beta-oxidation defects, LPIN1
      mutations, inborn errors of glycogenolysis and glycolysis, more rarely
      mitochondrial respiratory chain deficiency, purine defects and peroxysomal alpha
      methyl-acyl-CoA-racemase defect (AMACR), ii) structural causes with muscle
      dystrophies and myopathies, iii) calcium pump disorder with RYR1 gene mutations,
      iv) inflammatory causes with myositis. Irrespective of the cause of
      rhabdomyolysis, the pathology follows a common pathway, either by the direct
      injury to sarcolemma by increased intracellular calcium concentration (acquired
      causes) or by the failure of energy production (inherited causes), which leads to
      fiber necrosis. Rhabdomyolysis are frequently precipitated by febrile illness or
      exercise. These conditions are associated with two events, elevated temperature
      and high circulating levels of pro-inflammatory mediators such as cytokines and
      chemokines. To illustrate these points in the context of energy metabolism,
      protein thermolability and the potential benefits of arginine therapy, we focus
      on a rare cause of rhabdomyolysis, aldolase A deficiency. In addition, our
      studies on lipin-1 (LPIN1) deficiency raise the possibility that several diseases
      involved in rhabdomyolysis implicate pro-inflammatory cytokines and may even
      represent primarily pro-inflammatory diseases. Thus, not only thermolability of
      mutant proteins critical for muscle function, but also pro-inflammatory cytokines
      per se, may lead to metabolic decompensation and rhabdomyolysis. 

PMID- 25778940
TI  - A new case of UDP-galactose transporter deficiency (SLC35A2-CDG): molecular
      basis, clinical phenotype, and therapeutic approach.
AB  - Congenital disorders of glycosylation (CDG) are a group of hereditary metabolic
      diseases characterized by abnormal glycosylation of proteins and lipids. Often,
      multisystem disorders with central nervous system involvement and a large variety
      of clinical symptoms occur. The main characteristics are developmental delay,
      seizures, and ataxia. In this paper we report the clinical and biochemical
      characteristics of a 5-year-old girl with a defective galactosylation of N
      glycans, resulting in developmental delay, muscular hypotonia, epileptic
      seizures, inverted nipples, and visual impairment. Next generation sequencing
      revealed a de novo mutation (c.797G > T, p.G266V) in the X-chromosomal gene
      SLC35A2 (solute carrier family 35, UDP-galactose transporter, member A2; MIM
      300896). While this mutation was found heterozygous, random X-inactivation of the
      normal allele will lead to loss of normal SLC35A2 activity in respective cells.
      The functional relevance of the mutation was demonstrated by complementation of
      UGT-deficient MDCK-RCA(r) and CHO-Lec8 cells by normal UGT-expression construct
      but not by the mutant version. The effect of dietary galactose supplementation on
      glycosylation was investigated, showing a nearly complete normalization of
      transferrin glycosylation. 

PMID- 25778942
TI  - Erratum to: TMEM70 deficiency: long-term outcome of 48 patients.

PMID- 25778943
TI  - Christian Korner.

PMID- 25778941
TI  - Spectrum of combined respiratory chain defects.
AB  - Inherited disorders of mitochondrial energy metabolism form a large and
      heterogeneous group of metabolic diseases. More than 250 gene defects have been
      reported to date and this number continues to grow. Mitochondrial diseases can be
      grouped into (1) disorders of oxidative phosphorylation (OXPHOS) subunits and
      their assembly factors, (2) defects of mitochondrial DNA, RNA and protein
      synthesis, (3) defects in the substrate-generating upstream reactions of OXPHOS,
      (4) defects in relevant cofactors and (5) defects in mitochondrial homeostasis.
      Deficiency of more than one respiratory chain enzyme is a common finding.
      Combined defects are found in 49 % of the known disease-causing genes of
      mitochondrial energy metabolism and in 57 % of patients with OXPHOS defects
      identified in our diagnostic centre. Combined defects of complexes I, III, IV and
      V are typically due to deficiency of mitochondrial DNA replication, RNA
      metabolism or translation. Defects in cofactors can result in combined defects of
      various combinations, and defects of mitochondrial homeostasis can result in a
      generalised decrease of all OXPHOS enzymes. Noteworthy, identification of
      combined defects can be complicated by different degrees of severity of each
      affected enzyme. Furthermore, even defects of single respiratory chain enzymes
      can result in combined defects due to aberrant formation of respiratory chain
      supercomplexes. Combined OXPHOS defects have a great variety of clinical
      manifestations in terms of onset, course severity and tissue involvement. They
      can present as classical encephalomyopathy but also with hepatopathy,
      nephropathy, haematologic findings and Perrault syndrome in a subset of
      disorders.

PMID- 25778944
TI  - Bismetal Complexes of 5,20-Bis(5-formyl-2-pyrrolyl)-[26]hexaphyrin(1.1.1.1.1.1)
      Exhibiting Strong Near-Infrared Region Absorptions.
AB  - [26]Hexaphyrin(1.1.1.1.1.1) bearing two 5-formyl-2-pyrrolyl groups at the 5- and
      20-positions was prepared by cross-condensation of 5,10-bis(pentafluorophenyl)
      substituted tripyrrane with 2,5-diformylpyrrole as an effective binuclear metal
      coordinating ligand, owing to the two hemiporphyrin-like NNNN pockets. In fact,
      metalation of this hexaphyrin with Zn(II) , Cu(II) , and Pd(II) salts proceed
      smoothly at room temperature to give the corresponding bismetal complexes that
      displayed remarkably redshifted absorption spectra reaching deep into near
      infrared region. These redshifted absorption bands are ascribed, through
      electrochemical investigations and DFT calculations, to two structural motifs:
      the N-metalopyrrole substructure that elevates the HOMO level due to the electron
      donating property and the two coordinated metal ions that serve as Lewis acids to
      lower the LUMO level. 

PMID- 25778945
TI  - Microalbuminuria in obstructive sleep apnea syndrome.
AB  - OBJECTIVES: Microalbuminuria is an important risk factor for cardiovascular
      diseases. Microalbuminuria may be seen due to intermittent hypoxemia in patients
      with obstructive sleep apnea syndrome (OSAS). In this study, we investigated the
      prevalence and relationship of microalbuminuria with clinical and physiological
      parameters in patients with OSAS. METHOD: Ninety-eight patients with OSAS and 26
      nonapneic snoring subjects upon polysomnography were included in this study. The
      urinary albumin-to-creatinine ratio (UACR) was calculated according to a
      previously described formula. The severity index of chronic diseases was
      evaluated by using the modified cumulative illness rating scale (MCIRS). Insulin
      resistance (IR) method was analyzed by homeostasis assessment model (HOMA-IR).
      Subjective sleepiness was assessed using the Epworth sleepiness scale (ESS).
      RESULTS: Body mass index (BMI), MCIRS, and UACR were higher in patients with OSAS
      than nonapneic snoring subjects. In linear regression model, there was a negative
      relationship between UACR and minimal O2, and there was a significantly positive
      relationship between UACR and desaturation index. CONCLUSION: Microalbuminuria
      may be seen in patients with OSAS, depending on the severity of disease and
      hypoxemia. Microalbuminuria in patients with OSAS should be examined in regular
      periods for risk of cardiovascular morbidity or mortality.

PMID- 25778946
TI  - Mandibular advancement splint (MAS) therapy for obstructive sleep apnoea--an
      overview and quality assessment of systematic reviews.
AB  - BACKGROUND: To conduct an overview of existing systematic reviews concerning
      management of obstructive sleep apnoea-hypopnoea syndrome (OSAHS) with mandibular
      advancement splint (MAS) and assess their methodological quality. METHOD: PubMed
      and relevant Cochrane Library databases (CDSR, DARE, HTA) searches were performed
      (09.13) to identify systematic reviews investigating the response of adults with
      OSAHS to MAS therapy. The methodological quality of the included systematic
      reviews was assessed using AMSTAR, a validated tool for assessing quality.
      RESULTS: Eight systematic reviews, four incorporating meta-analyses, were
      identified evaluating both objective and subjective outcome measures. The
      effectiveness of MAS therapy was compared to no treatment (n = 1), non-active
      appliance (n = 6), continuous positive airway pressure (CPAP; n = 5), surgical
      intervention (n = 3) and a different MAS intervention (n = 4). The quality of the
      reviews was variable (median = 7, range = 3 to 11), with only two of higher
      quality (AMSTAR scores >10), one of them a Cochrane review. In this high quality
      and current review, the overall (pooled) effects for comparison of MAS therapy
      with inactive appliances, revealed significant benefits of MAS therapy in terms
      of both daytime sleepiness and objective apnoea-hypopnoea index (AHI) outcomes.
      CONCLUSION: In general, the results from the higher quality reviews concerning
      the effectiveness of MAS therapy for OSAHS highlight the ability of the
      intervention to improve OSAHS. Current reporting guidelines for systematic
      reviews (e.g. PRISMA) and sources of high-quality existing reviews should be
      closely followed to enhance the validity and relevance of future reviews.

PMID- 25778947
TI  - Severe obstructive sleep apnea increases left atrial volume independently of left
      ventricular diastolic impairment.
AB  - PURPOSE: Severe obstructive sleep apnea (OSA) directly impairs left ventricular
      (LV) diastolic function. Left atrial volume index (LAVI), an independent
      predictor of future cardiovascular events, is also related to OSA severity. This
      study aimed to assess whether OSA is associated with an increase in LAVI
      independently of LV diastolic function. METHODS: Two hundred six OSA patients
      (apnea hypopnea index, AHI >= 5/h) without cardiac disease, hypertension, and
      diabetes were enrolled. They underwent overnight fully attended polysomnography
      and 2-dimensional echocardiography in order to estimate LA volumes and LV
      diastolic function which was assessed by the ratio of transmitral early diastolic
      flow velocity to late diastolic flow velocity (E/A), deceleration time, and
      mitral annular velocity (e') which was derived from tissue Doppler imaging.
      Patients were divided into two groups based on AHI, namely, group M (5 <= AHI <
      30/h) and group S (AHI >= 30/h). RESULTS: The LAVI value in group S was
      significantly larger than that in group M (20 +/- 5 vs. 23 +/- 5 mL/m(2), P <
      0.001). E/A in group S was significantly lower than that in group M (P < 0.001),
      whereas the ratio of E to e' (E/e') in group S was significantly higher than that
      in group M (P < 0.001). AHI showed a statistically significant correlation with
      LAVI (P < 0.001). On multivariate linear regression analysis, severe OSA was
      independently related with LAVI even after adjusting for age, sex, systolic blood
      pressure, body mass index, and measurements of LV diastolic function (P = 0.04).
      CONCLUSIONS: Severe OSA itself might directly increase LAVI, independently of LV
      diastolic function.

PMID- 25778948
TI  - Genetic structure characterization of Chileans reflects historical immigration
      patterns.
AB  - Identifying the ancestral components of genomes of admixed individuals helps
      uncovering the genetic basis of diseases and understanding the demographic
      history of populations. We estimate local ancestry on 313 Chileans and assess the
      contribution from three continental populations. The distribution of ancestry
      block-length suggests an average admixing time around 10 generations ago. Sex
      chromosome analyses confirm imbalanced contribution of European men and Native
      American women. Previously known genes under selection contain SNPs showing large
      difference in allele frequencies. Furthermore, we show that assessing ancestry is
      harder at SNPs with higher recombination rates and easier at SNPs with large
      difference in allele frequencies at the ancestral populations. Two observations,
      that African ancestry proportions systematically decrease from North to South,
      and that European ancestry proportions are highest in central regions, show that
      the genetic structure of Chileans is under the influence of a diffusion process
      leading to an ancestry gradient related to geography. 

PMID- 25778982
TI  - Identification of biomarkers regulated by rexinoids (LGD1069, LG100268 and Ro25
      7386) in human breast cells using Affymetrix microarray.
AB  - Retinoids possess anti-proliferative properties, which suggests that they possess
      chemopreventive and therapeutic potential against cancer. In the current study,
      genes modulated by rexinoids (retinoid X receptor (RXR)-pan agonists, LGD1069 and
      LG100268; and the RXRalpha agonist, Ro25-7386) were identified using an
      Affymetrix microarray in normal and malignant breast cells. It was observed that
      LGD1069, LG100268 and Ro25-7386 suppressed the growth of breast cells. Secondly,
      several rexinoid-regulated genes were identified, which are involved in cell
      death, cell growth/maintenance, signal transduction and response to stimulus.
      These genes may be associated with the growth-suppressive activity of rexinoids.
      Therefore, the identified genes may serve as biomarkers and novel molecular
      targets for the prevention and treatment of breast cancer.

PMID- 25778983
TI  - Diastereoselective tandem reactions of substituted 3-sulfolenes with bis-vinyl
      ketones leading to highly functionalized bicyclic and tricyclic frameworks.
AB  - The base-promoted reaction of 3-sulfolene with bis-vinyl ketones was shown in
      earlier work to proceed through a gamma-1,2 addition/anionic oxy-Cope cascade; a
      subsequent treatment with base induced a second gamma-1,2 addition to provide a
      [3.3.0] bicyclic framework that our group then exploited in the design of
      rigidified enzyme inhibitors for influenza neuraminidase. Out of a desire to
      expand the range of structural archetypes accessible through these couplings (and
      hopefully access additional conformationally-constrained inhibitor platforms) we
      have revisited this methodology, this time using substituted starting reagents.
      We show that judicious choice of the newly added substituent can control the
      exclusive formation of one of four new structural types, each formed as a single
      diastereomer. These include bicyclo[3.2.1] sulfones and spiro[5.4] sulfones, as
      well as an expanded collection of our original bicyclo[3.3.0] sulfone scaffolds,
      this time incorporating adjacent quaternary centres or additional rings. 

PMID- 25778984
TI  - Conversion of central serous chorioretinopathy to polypoidal choroidal
      vasculopathy.

PMID- 25778985
TI  - Regulation of Iron Uptake by IRT1: Endocytosis Pulls the Trigger.

PMID- 25778986
TI  - Identification of Early Nuclear Target Genes of Plastidial Redox Signals that
      Trigger the Long-Term Response of Arabidopsis to Light Quality Shifts.
AB  - Natural illumination conditions are highly variable and because of their sessile
      life style, plants are forced to acclimate to them at the cellular and molecular
      level. Changes in light intensity or quality induce changes in the
      reduction/oxidation (redox) state of the photosynthetic electron chain that acts
      as a trigger for compensatory acclimation responses comprising functional and
      structural adjustments of photosynthesis and metabolism. Such responses include
      redox-controlled changes in plant gene expression in the nucleus and organelles.
      Here we describe a strategy for the identification of early redox-regulated genes
      (ERGs) in the nucleus of the model organism Arabidopsis thaliana that respond
      significantly 30 or 60 min after the generation of a reduction signal in the
      photosynthetic electron transport chain. By comparing the response of wild-type
      plants with that of the acclimation mutant stn7, we could specifically identify
      ERGs. The results reveal a significant impact of chloroplast redox signals on
      distinct nuclear gene groups including genes for the mitochondrial electron
      transport chain, tetrapyrrole biosynthesis, carbohydrate metabolism, and
      signaling lipid synthesis. These expression profiles are clearly different from
      those observed in response to the reduction of photosynthetic electron transport
      by high light treatments. Thus, the ERGs identified are unique to redox
      imbalances in photosynthetic electron transport and were then used for analyzing
      potential redox-responsive cis-elements, trans-factors, and chromosomal
      regulatory hot spots. The data identify a novel redox-responsive element and
      indicate extensive redox control at transcriptional and chromosomal levels that
      point to an unprecedented impact of redox signals on epigenetic processes.

PMID- 25778987
TI  - Improved working memory performance following administration of a single dose of
      American ginseng (Panax quinquefolius L.) to healthy middle-age adults.
AB  - OBJECTIVE: A ginsenoside-rich extract of American ginseng (Panax quinquefolius
      L.), Cereboost(TM), was previously shown to improve working memory and mood in
      healthy young individuals. The present study represented a partial replication
      investigating whether these effects extended to healthy middle-aged individuals.
      METHODS: Fifty-two healthy volunteers (40-60 years old, mean age 51.63) received
      200 mg of P. quinquefolius or a matching placebo according to a double-blind,
      placebo-controlled, balanced, crossover design. The Cognitive Drug Research
      battery and the Computerised Mental Performance Assessment System were used to
      evaluate cognitive performance at baseline then 1, 3 and 6 h following treatment.
      Blood glucose and mood were co-monitored. RESULTS: Compared with placebo, P.
      quinquefolius improved cognitive performance on 'Working Memory' factor at 3 h.
      Similar effects were observed in one of the two tasks making up this factor,
      spatial working memory. There were no significant effects on mood or blood
      glucose levels. CONCLUSIONS: These data confirm that P. quinquefolius can acutely
      benefit working memory and extend the age range of this effect to middle-aged
      individuals. These changes are unlikely to be underpinned by modulation of blood
      glucose in this population.

PMID- 25778989
TI  - C4d immunostaining is an independent predictor of cardiac allograft vasculopathy
      and death in heart transplant recipients.
AB  - Antibody-mediated rejection (AMR) occurs in 10-20% of patients after heart
      transplantation. C4d immunostaining is one parameter used in its diagnosis. This
      study aimed to determine whether C4d staining has prognostic significance for
      mortality, coronary allograft vasculopathy (CAV), cell-mediated rejection (CMR),
      and graft dysfunction in patients post-transplantation. Consecutive patients
      receiving an endomyocardial biopsy between 2007 and 2008 were selected. Left
      ventricular function, angiography, episodes of AMR/CMR, and death were noted. C4d
      was graded from 0 to 3 (immunostaining). Cox proportional models (recurrent
      events analysis) were used to evaluate C4d staining with mortality, graft
      dysfunction, CAV (>=grade 2), and episodes of >=2R-CMR. We analyzed 2525 biopsy
      specimens (n = 217). During a follow-up of 4.5 +/- 2 years, 35 died, 49 had graft
      dysfunction, seven had >=grade 2 CAV, and 95 episodes of CMR occurred. A one
      grade increase in C4d staining was associated with an increase in mortality (HR
      1.57; 95% CI 1.0-2.5), a higher risk of CAV (HR 2.4, 95% CI 1.04-5.4), and a
      trend toward graft dysfunction (HR 1.42; 95% CI 1.0-2.09). C4d was not associated
      with CMR. C4d immunostaining was a significant predictor of CAV and death but not
      subsequent episodes of CMR. There was also a trend toward increased graft
      failure.

PMID- 25778990
TI  - Synthesis and biological screening of 2'-aryl/benzyl-2-aryl-4-methyl-4',5
      bithiazolyls as possible anti-tubercular and antimicrobial agents.
AB  - A series of 2'-aryl/benzyl-2-aryl-4-methyl-4',5-bithiazolyl derivatives, 25-64
      were synthesized and evaluated for inhibitory activity against Mycobacterium
      smegmatis MC(2) 155 strain and antimicrobial activities against four pathogenic
      bacteria Bacillus subtilis, Staphylococcus aureus, Escherichia coli and Proteus
      vulgaris. Among them, compounds 40, 49, 50, and 54 exhibited moderate to good
      inhibition on the growth of the bacteria Mycobacterium smegmatis at the
      concentration of 30 MUM. Compounds 26, 40, 44, 54 and 56 exhibited moderate to
      good antibacterial activity. Compound 5-(2'-(4-fluorobenzyl)thiazol-4'-yl)-2-(4
      fluorophenyl)-4-methyl-thiazole (54) exhibited both antitubercular as well as
      antimicrobial activity against all tested strains.

PMID- 25778991
TI  - Design, synthesis and evaluation of scutellarein-O-alkylamines as multifunctional
      agents for the treatment of Alzheimer's disease.
AB  - A series of scutellarein-O-alkylamine derivatives were designed, synthesized and
      tested as multifunctional agents for the treatment of Alzheimer's disease (AD).
      The results showed that most of these compounds exhibited good multifunctional
      activities. Among them, compound 16d demonstrated significant metal chelating
      properties, moderate acetylcholinesterase (AChE) inhibitory and anti-oxidative
      activity, and excellent inhibitory effects on self-induced Abeta(1-42)
      aggregation, Cu(2+)-induced Abeta(1-42) aggregation, human AChE-induced Abeta(1
      40) aggregation and disassembled Cu(2+)-induced aggregation of the well
      structured Abeta(1-42) fibrils. Both kinetic analysis of AChE inhibition and
      molecular modeling study suggested that 16d binds simultaneously to the catalytic
      active site and peripheral anionic site of AChE. Moreover, compound 16d showed a
      good protective effect against H2O2-induced PC12 cell injury, with low toxicity
      in SH-SY5Y cells. Furthermore, the step-down passive avoidance test showed this
      compound significantly reversed scopolamine-induced memory deficit in mice. Thus,
      16d was shown to be an interesting multifunctional lead compound worthy of
      further study.

PMID- 25778992
TI  - Aza-isoindolo and isoindolo-azaquinoxaline derivatives with antiproliferative
      activity.
AB  - Three new ring systems, pyrido[2',3':3,4]pyrrolo[1,2-a]quinoxalines,
      pyrido[3',2':3,4]pyrrolo[1,2-a]quinoxalines and pyrido[2',3':5,6]pyrazino[2,1
      a]isoindoles, were synthesized through an aza-substitution on the already active
      isoindolo-quinoxaline system and in particular in the position 7 or 4 of the
      isoindole moiety and in position 5 of the quinoxaline portion. All new compounds
      were screened by the National Cancer Institute (Bethesda, MD) against a panel of
      60 human tumor cell lines. Biological results of the most active derivatives,
      with pGI50 values between 7.09 and 7.27, confirmed the importance of the presence
      of methoxy substituents for biological activity. The anti-proliferative effect of
      selected quinoxalines was associated with apoptosis of the cells and arrest in
      G2/M phase of the cell cycle. DNA binding properties of the compounds was also
      assessed to investigate the possible mechanism of action. 

PMID- 25778993
TI  - Discovery of InhA inhibitors with anti-mycobacterial activity through a matched
      molecular pair approach.
AB  - The Mycobacterium tuberculosis (M. tuberculosis) enoyl-acyl carrier protein
      reductase (mtInhA) is an attractive enzyme and a thoroughly studied target for
      tuberculosis therapy. In this study, to identify novel structure-activity
      relationships (SARs) of mtInhA inhibitors, a series of diphenyl ether derivatives
      were designed based on the matched molecular pair (MMP) method, and the binding
      energies of these compounds were subsequently estimated by in silico structure
      based drug screening (SBDS) to provide more useful data. Consequently, the 10
      unique candidate compounds (KEM1-KEM10) were identified and assessed for the
      inhibition of mtInhA enzymatic activity, in vitro antibiotic effects against
      model mycobacteria and toxicity level on both intestinal bacteria and mammalian
      cells. Among the compounds tested, phenyl group (KEM4) and 2-fluorobenzyl group
      (KEM7) substitutions produced preferable inhibitory effects on mtInhA enzymatic
      activity relative to those provided by a furyl group (KES4: base compound) at the
      terminal of the compound, and KEM7 inhibited the growth of the mycobacteria
      strain with a lower IC50 value. Moreover, most of the candidate compounds
      exhibited neither inhibition of the growth of enterobacteria nor toxic effects on
      mammalian cells, though KEM10 exhibited toxicity against cultured MDCK cells. The
      structural and experimental information concerning these mtInhA inhibitors
      identified through MMP-based in silico screening will likely contribute to the
      lead optimisation of novel antibiotics for M. tuberculosis.

PMID- 25778994
TI  - Design of a serotonin 4 receptor radiotracer with decreased lipophilicity for
      single photon emission computed tomography.
AB  - With the aim to develop a suitable radiotracer for the brain imaging of the
      serotonin 4 receptor subtype (5-HT4R) using single photon emission computed
      tomography (SPECT), we synthesized and evaluated a library of di- and
      triazaphenanthridines with lipophilicity values which were in the range expected
      to favour brain penetration, and which demonstrated specific binding to the
      target of interest. Adding additional nitrogen atoms to previously described
      phenanthridine ligands exhibiting a high unspecific binding, we were able to
      design a radioiodinated compound [(125)I]14. This compound exhibited a binding
      affinity value of 0.094 nM toward human 5-HT4R and a high selectivity over other
      serotonin receptor subtypes (5-HTR). In vivo SPECT imaging studies and
      competition experiments demonstrated that the decreased lipophilicity (in
      comparison with our previously reported compounds 4 and 5) allowed a more
      specific labelling of the 5-HT4R brain-containing regions.

PMID- 25778995
TI  - Design and synthesis of potent 1,2,4-trisubstituted imidazolinone derivatives
      with dual p38alphaMAPK and ERK1/2 inhibitory activity.
AB  - The synthesis of new 1,2,4-trisubstituted imidazolinone derivatives was
      described. The new compounds were designed as dual p38alphaMAPK and ERK1/2
      inhibitors through hybridization of pharmacophoric elements associated with
      inhibition of these kinases. The kinase inhibition assay revealed excellent
      activity in the nanomolar range; especially compounds 6d and 7h which seemed
      promising candidates for such dual activity with IC50 values of 4.5 and 4.7 nM
      against p38alphaMAP, 25.0 and 24.0 nM against ERK1, and 3.2 and 3.5 nM against
      ERK2, respectively. These compounds were further tested for their
      antiproliferative activity against nine cancer cell lines, where they elicited
      high activity in the sub-micromolar range against breast, prostate and melanoma
      cells.

PMID- 25778996
TI  - Rapid prototyping of three-dimensional nanocomposite hydrogel constructs: effect
      of silica nanofiller on swelling and solute release behaviors of the
      nanocomposite hydrogels.
AB  - Three-dimensional (3D) patterning and engineering of biomaterials and
      biointerfaces have helped bioengineers harness the full potential of cell
      immobilization for different biomedical applications. However, the bioengineering
      of an efficient cell immobilized tool, having application in cell biology and
      tissue engineering, often comes into realization only when a cell friendly
      immobilization technique is combined with a compatible 3D patterning scheme. We
      have previously demonstrated the successful blue light induced
      photopolymerization of poly (ethyleneglycol) diacrylate (PEGDA) based hydrogels
      for the entrapment of Saccharomyces cerevisiae and NIH 3T3 fibroblast cells. In
      the present work we have modified rheology of the prepolymer solution by mixing
      fumed silica nanofiller in different concentrations. Here we demonstrate the
      rapid prototyping of cell immobilized nanocomposite hydrogels, where S.
      cerevisiae loaded nanofilled prepolymer solution was directly written in layer-by
      layer fashion using solid free form fabrication also known as rapid prototyping
      technique and was cross-linked into 3D cell loaded construct via blue light
      induced polymerization. The swelling trend was found to be a function of silica
      nanofiller concentration and transitioned from decreasing to increasing type at
      10% w/v nanofiller concentration. Dynamic swelling profile predicted that the
      swelling agent transported with in the gels via super case II type transport
      mechanism irrespective of the crosslink density. In contrast, the mode of
      transportation of the loaded solute was found to be fickian and nonfickian type
      respectively for loosely and tightly crosslinked gels. Spatial heterogeneity in
      the crosslinked network was resulted upon blue light curing, subsequently the 3D
      growth of the immobilized cells was observed to be a function of crosslink
      density.

PMID- 25778997
TI  - Is it necessary to retain the tensor tympani tendon in tympanoplasty?
AB  - OBJECTIVES/HYPOTHESIS: To evaluate the acoustic effect after canal wall-down
      tympanoplasty with sectioning of the tensor tympani muscle (TTM) tendon in
      patients with chronic otitis media. STUDY DESIGN: Prospective, controlled
      clinical trial. METHODS: From January 2010 to April 2014, 212 patients underwent
      canal wall-down tympanoplasty with ossicular chain reconstruction in one-stage
      surgery. For this study, the patients were assigned to two groups. In group 1
      (107 patients), the TTM tensor would be removed during the surgery, whereas it
      would be retained in group 2 (105 patients). Pre- and postoperative air
      conduction and bone conduction thresholds at 0.5, 1, 2, and 4 kHz were reported,
      and the air-bone gaps (ABGs) were measured. RESULTS: Mean postoperative ABG was
      16.0 dB in group 1 and 17.0 dB in group 2 and the ABG closure was 11.9 +/- 8.5 in
      group 1 and 11.8 +/- 9.7 in group 2. Both were not statistically different (P =
      .2381 and P = .9625). Overall, 84.1% of patients in group 1 and 75.2% of patients
      in group 2 attained a postoperative ABG of 20 dB or less. Success rate in group 1
      is slightly higher than group 2, but not significant (P = .1255). CONCLUSIONS:
      The section of the tensor tympani muscle tendon in canal wall-down tympanoplasty
      with ossiculoplasty had no statistically significant influence on sound
      transmission and can be a safe maneuver in middle ear surgery. LEVEL OF EVIDENCE:
      4

PMID- 25778998
TI  - Validation of reference genes for quantitative real-time PCR in Perigord black
      truffle (Tuber melanosporum) developmental stages.
AB  - The symbiotic fungus Tuber melanosporum Vittad. (Perigord black truffle) belongs
      to the Ascomycota and forms mutualistic symbiosis with tree and shrub roots. This
      truffle has a high value in a global market and is cultivated in many countries
      of both hemispheres. The publication of the T. melanosporum genome has given
      researchers unique opportunities to learn more about the biology of the fungus.
      Real-time quantitative PCR (qRT-PCR) is a definitive technique for quantitating
      differences in transcriptional gene expression levels between samples. To
      facilitate gene expression studies and obtain more accurate qRT-PCR data,
      normalization relative to stable housekeeping genes is required. These
      housekeeping genes must show stable expression under given experimental
      conditions for the qRT-PCR results to be accurate. Unfortunately, there are no
      studies on the stability of housekeeping genes used in T. melanosporum
      development. In this study, we present a morphological and microscopical
      classification of the developmental stages of T. melanosporum fruit body, and
      investigate the expression levels of 12 candidate reference genes (18S rRNA; 5.8S
      rRNA; Elongation factor 1-alpha; Elongation factor 1-beta; alpha-tubulin; 60S
      ribosomal protein L29; beta-tubulin; 40S ribosomal protein S1; 40S ribosomal
      protein S3; Glucose-6-phosphate dehydrogenase; beta-actin; Ubiquitin-conjugating
      enzyme). To evaluate the suitability of these genes as endogenous controls, five
      software-based approaches and one web-based comprehensive tool (RefFinder) were
      used to analyze and rank the tested genes. We demonstrate here that the 18S rRNA
      gene shows the most stable expression during T. melanosporum development and that
      a set of three genes, 18S rRNA, Elongation factor 1-alpha and 40S ribosomal
      protein S3, is the most suitable to normalize qRT-PCR data from all the analyzed
      developmental stages; conversely, 18S rRNA, Glucose-6-phosphate dehydrogenase and
      Elongation factor 1-alpha are the most suitable genes for fruiting body
      developmental stages. 

PMID- 25778999
TI  - Multilocus variable-number tandem-repeat analysis of Neisseria meningitidis
      serogroup C in China.
AB  - This study characterized Neisseria meningitidis serogroup C strains in China in
      order to establish their genetic relatedness and describe the use of multilocus
      variable-number tandem-repeat (VNTR) analysis (MLVA) to provide useful
      epidemiological information. A total of 215 N. meningitidis serogroup C strains,
      obtained from 2003 to 2012 in China, were characterized by MLVA with different
      published schemes as well as multilocus sequence typing. (i) Based on the MLVA
      scheme with a combination of five highly variable loci, 203 genotypes were
      identified; this level of discrimination supports its use for resolving closely
      related isolates. (ii) Based on a combination of ten low variable loci, clear
      phylogenetic relationships were established within sequence type complexes. In
      addition, there was evidence of microevolution of VNTR loci over the decade as
      strain lineages spread from Anhui to other provinces, the more distant the
      provinces from Anhui, the higher the genetic variation. 

PMID- 25779000
TI  - Most patients with HCV-associated lymphoma present with mild liver disease: a
      call to revise antiviral treatment prioritization.
AB  - BACKGROUND & AIMS: Hepatitis C virus (HCV) is associated with development of B
      cell non-Hodgkin lymphoma (HCV-NHL). Antiviral therapy (AVT) is prioritized in
      HCV-infected patients with significant fibrosis/cirrhosis. It is unknown whether
      current recommendations based on liver parameters cover the risk of HCV-NHL
      development. We aimed to evaluate the liver disease stages of patients with HCV
      NHL. METHODS: Hepatitis C virus-NHL patients seen at MD Anderson Cancer Center
      between 2008 and 2014 were evaluated for underlying liver disease within a year
      of HCV-NHL diagnosis by non-invasive fibrosis markers, radiology or liver biopsy.
      Included patients were observed retrospectively (2008-2012) or prospectively
      (2012-2014). RESULTS: Eighty nine patients with HCV-NHL were evaluated. Most
      patients had genotype 1 (62%) infection, had diffuse large B cell lymphomas
      (62%), and detectable HCV RNA (90%) at NHL diagnosis. Notably, advanced liver
      disease (Metavir stage >= 3) was present in only 18% of the patients at the time
      of HCV-NHL diagnosis. All 53 patients with chronic HCV infection documented
      before lymphoma diagnosis were seen by HCV-treating physicians. Providers did not
      recommend AVT in almost one half of cases (44%), mostly because of the lack of
      advanced liver disease at HCV diagnosis (38%). CONCLUSIONS: Most patients with
      HCV-NHL have mild liver disease at cancer diagnosis. Our findings suggest the
      need for early initiation of AVT in infected patients to eradicate HCV infection
      and its extra-hepatic manifestations. Treatment prioritization and cost must be
      weighed against the potential benefits of preventing NHL.

PMID- 25779001
TI  - Crystal structure of an SH2-kinase construct of c-Abl and effect of the SH2
      domain on kinase activity.
AB  - Constitutive activation of the non-receptor tyrosine kinase c-Abl (cellular
      Abelson tyrosine protein kinase 1, Abl1) in the Bcr (breakpoint cluster region)
      Abl1 fusion oncoprotein is the molecular cause of chronic myeloid leukaemia
      (CML). Recent studies have indicated that an interaction between the SH2 (Src
      homology 2) domain and the N-lobe (N-terminal lobe) of the c-Abl kinase domain
      (KD) has a critical role in leukaemogenesis [Grebien et al. (2011) Cell 147, 306
      319; Sherbenou et al. (2010) Blood 116, 3278-3285]. To dissect the structural
      basis of this phenomenon, we studied c-Abl constructs comprising the SH2 and KDs
      in vitro. We present a crystal structure of an SH2-KD construct bound to
      dasatinib, which contains the relevant interface between the SH2 domain and the N
      lobe of the KD. We show that the presence of the SH2 domain enhances kinase
      activity moderately and that this effect depends on contacts in the SH2/N-lobe
      interface and is abrogated by specific mutations. Consistently, formation of the
      interface decreases slightly the association rate of imatinib with the KD. That
      the effects are small compared with the dramatic in vivo consequences suggests an
      important function of the SH2-N-lobe interaction might be to help disassemble the
      auto-inhibited conformation of c-Abl and promote processive phosphorylation,
      rather than substantially stimulate kinase activity. 

PMID- 25779003
TI  - Molecular characterization and phylogeny of Kalotermes populations from the
      Levant, and description of Kalotermes phoeniciae sp. nov.
AB  - The presence of the yellow-necked drywood termite, Kalotermes flavicollis Fabr.,
      has been reported along most of the Mediterranean coasts of Europe, Africa and
      Asia. While morphological and genetic data exist on European K. flavicollis
      populations from western and central Mediterranean regions, data on eastern
      Mediterranean Kalotermes are scarce, and no genetic data exist to date. In this
      study, we analyzed 17 Kalotermes sp. colonies from 11 localities in the Levant
      (Cyprus, Lebanon, and Israel), in order to characterize genetically
      (mitochondrial DNA: COII, 16S, and control region) these populations. We found
      that samples from the Levant are genetically different from K. flavicollis, with
      distance values falling in the range of interspecific distances. In the phylogeny
      of European Kalotermes populations, samples from the Levant form a clade of their
      own, sister to a clade including K. flavicollis and Kalotermes italicus. Inside
      the eastern Mediterranean clade, all the samples from Cyprus are included in a
      well-supported subclade, suggesting that the colonization of the island might
      have occurred in a single event. These findings show that the populations we
      examined do not belong to the species K. flavicollis, but to a new species
      peculiar to the Levant, that we describe as Kalotermes phoeniciae sp. nov. It is
      possible that previous reports of K. flavicollis in this region can be attributed
      to K. phoeniciae. 

PMID- 25779002
TI  - Crossing the embryonic midline: molecular mechanisms regulating axon
      responsiveness at an intermediate target.
AB  - In bilaterally symmetric animals, the precise assembly of neural circuitry at the
      midline is essential for coordination of the left and right sides of the body.
      Commissural axons must first be directed across the midline and then be prevented
      from re-crossing in order to ensure proper midline connectivity. Here, we review
      the attractants and repellents that direct axonal navigation at the ventral
      midline and the receptors on commissural neurons through which they signal. In
      addition, we discuss the mechanisms that commissural axons use to switch their
      responsiveness to midline-derived cues, so that they are initially responsive to
      midline attractants and subsequently responsive to midline repellents.

PMID- 25779004
TI  - Diagnosis of Sarcoidosis.
AB  - The diagnosis of sarcoidosis, a systemic granulomatous disease, is based on a
      compatible clinical-radiological picture and the histological evidence of
      noncaseating granulomas. Other diseases mimicking sarcoidosis, mostly infections
      and other granulomatoses, have to be excluded. There is no single test for
      sarcoidosis, and the presence of granulomas alone does not establish the
      diagnosis. Symptoms of sarcoidosis are not specific and can be markedly different
      according to organ involvement and disease course. Respiratory symptoms and
      fatigue are the most common symptoms at any stage of disease. Histological
      confirmation is not needed for Lofgren's or Heerfordt's syndrome and asymptomatic
      bihilar lymphadenopathy. The radiological staging system is still based on chest
      radiography, and computed tomography is not mandatory for routine follow-up.
      (18)F-fluorodeoxyglucose positron emission tomography may be of value in special
      cases. For assessment of lung involvement and follow-up, pulmonary function tests
      are necessary with vital capacity being the most important single parameter and
      diffusion capacity the most sensitive. Bronchoscopy with biopsy is the most
      common procedure for detection of granulomas, when there is no easier biopsy site
      like skin or peripheral lymph nodes. Endobronchial ultrasonography-guided
      transbronchial needle aspiration has replaced mediastinoscopy for evaluation of
      mediastinal and hilar lymph nodes with a high diagnostic yield. Despite numerous
      studies, no single biomarker can be reliably used for correct diagnosis or
      exclusion of sarcoidosis. Genetic testing, despite promising advances, has still
      not been included in routine care for sarcoidosis patients. The long-term
      prognosis of sarcoidosis depends on the different organ manifestations: Cardiac
      or central nervous involvement, together with respiratory complications, is
      critical. A multidisciplinary approach is necessary for comprehensive care of the
      sarcoidosis patient. 

PMID- 25779005
TI  - Molecular analysis of products of conception obtained by hysteroembryoscopy from
      infertile couples.
AB  - PURPOSE: To analyze the molecular cytogenetic data obtained from products of
      conception (POC) obtained by selective biopsy of first trimester miscarriages and
      to estimate the rate of chromosomal anomalies in miscarriages from pregnancies
      achieved by natural conception (NC) or by assisted reproductive technology (ART)
      interventions. METHODS: We used KaryoLiteTM BoBsTM (PerkinElmer LAS, Wallac,
      Turku, Finland) technology to analyze 189 samples from ART or NC pregnancies.
      RESULTS: All POC were successfully evaluated. A higher incidence of chromosomal
      abnormalities was observed in POC after ART using the patient's own oocytes than
      from NC pregnancies (62.7% vs. 40.6%; p < 0.05). The lowest incidence of
      chromosomal abnormalities was observed in POCs ART using donor eggs from women
      younger than 35 years (12.8%). No statistical differences in the percentage of
      abnormal miscarriages were observed in correlation with sperm concentration: a
      sperm concentration less than 5 million/mL produced 75% abnormal results and a
      concentration higher than 5 million/mL produced 51%. CONCLUSIONS: POC analysis is
      essential to determine the cause of pregnancy loss. Using culture-independent
      molecular biology techniques to analyze POCs avoids limitations such as growth
      failure and reduces the time required for analysis. Selective biopsy of fetal
      tissue by hysteroembryoscopy avoids the risk of misdiagnosis due to maternal cell
      contamination. Our results show that maternal age, sperm quality, and ART
      assisted pregnancies are risk factors for abnormal gestations.

PMID- 25779006
TI  - Malignant EEG patterns in cardiac arrest patients treated with targeted
      temperature management who survive to hospital discharge.
AB  - BACKGROUND AND PURPOSE: Cardiac arrest patients treated with targeted temperature
      management (TTM) have improved neurological outcomes, however mortality remains
      high. EEG monitoring improves detection of malignant EEG patterns (MEPs), however
      their prevalence in patients surviving to hospital discharge is unknown.
      DESIGN/METHODS: We examined consecutive cardiac arrest subjects who received TTM
      and continuous EEG monitoring at one academic center. Only subjects surviving to
      hospital discharge were included in the analysis. MEPs were defined as seizures,
      status epilepticus, myoclonic status epilepticus, or generalized periodic
      discharges. Subjects with suppression-burst (SB) without concomitant MEPs were
      categorized as having a "pure" SB pattern. Demographic, survival, hospital
      discharge disposition, and neurological function data were recorded
      retrospectively. Outcomes were assessed using the Glasgow-Pittsburgh Cerebral
      Performance Category (CPC). A CPC score of 1-2 was considered "good" neurological
      function, and a CPC of 3-4 "poor". RESULTS: Of 364 admissions due to cardiac
      arrest screened, 120 (29.9%) survived to hospital discharge and met inclusion
      criteria. MEPs and pure SB were observed in 19 (15.8%) and 22 (18.3%) survivors
      respectively. Two subjects with MEP and eight subjects with pure SB had good
      neurological function at discharge, however all SB cases were confounded by the
      use of anesthetic agents. Presence of MEPs was not an independent predictor of
      poor neurological function (p=0.1). CONCLUSIONS: MEPs are common among cardiac
      arrest patients treated with induced hypothermia who survive to hospital
      discharge. Poor neurological function at discharge was not associated with MEPs.
      Prospective studies assessing the role of EEG monitoring in cardiac arrest
      prognostication are warranted.

PMID- 25779007
TI  - The incidence of "load&go" out-of-hospital cardiac arrest candidates for
      emergency department utilization of emergency extracorporeal life support: A one
      year review.
AB  - BACKGROUND: The outcome of patients after out-of-hospital cardiac arrest (OHCA)
      is poor and gets worse after prolonged resuscitation. Recently introduced
      attempts like an early installed emergency extracorporeal life support (E-ECLS)
      in patients with persisting cardiac arrest at the emergency department (ED) are
      tried. The "Vienna Cardiac Arrest Registry" (VICAR) was introduced August 2013 to
      collect Utstein-style data. The aim of this observational study was to identify
      the incidence of patients which fulfil "load&go"-criteria for E-ECLS at the ED.
      METHODS: VICAR was retrospectively analyzed for following criteria: age <75
      years; witnessed OHCA; basic life support; ventricular fibrillation/ventricular
      tachycardia; no return-of-spontaneous-circulation (ROSC) within 15 min of
      advanced-life-support, which were supposed as potential optimal criteria for
      "load&go" plus successful E-ECLS treatment at the ED. The observation period was
      from August 1, 2013 to July 31, 2014. RESULTS: Over 948 OHCA patients registered
      during the study period; data were exploitable for 864 patients. Of all patients,
      "load&go"-criteria were fulfilled by 55 (6%). However, 96 (11%) were transported
      with on-going CPR to the ED. Of these 96 patients, only 16 (17%) met the
      "load&go"-criteria. Similarly, among the 96 patients, 12 adults were treated with
      E-ECLS at the ED, with only 5 meeting the criteria. Among these 12 patients,
      favourable neurological outcome (CPC 1/2) was obtained in 1 patient without
      criteria. CONCLUSION: Further promotion of these criteria within the ambulance
      crews is needed. May be these criteria could serve as a decision support for
      emergency physicians/paramedics, which patients to transport with on-going CPR to
      the ED for E-ECLS.

PMID- 25779008
TI  - How effectively can young people perform dispatcher-instructed cardiopulmonary
      resuscitation without training?
AB  - AIMS: Survival from out-of-hospital cardiac arrest is increased by bystander
      cardiopulmonary resuscitation (CPR). Bystander performance can be improved when
      CPR instructions are delivered by a calltaker at the Emergency Communications
      Centre. Little is known about a young person's ability to understand these
      instructions and perform CPR correctly. We assessed the ability of a group of
      untrained young people to effectively apply these directions to an adult
      resuscitation manikin. METHODS: 87 youngsters aged 7-15 years with no previous
      training in CPR were separately equipped with a mobile phone and an adult
      assessment manikin. They phoned the emergency number (111) and were automatically
      diverted to a senior emergency medical dispatcher (EMD). The EMD delivered
      resuscitation instructions which complied fully with Medical Priority Dispatch
      System (version 12.1). Performance was monitored using a Laerdal Computerised
      Skill Reporting System. RESULTS: Average compression depth increased with age
      from 10.3 mm to 30 mm for 8 and 15 year olds respectively. 100 compressions per
      minute was achieved in youngsters aged 10 years and older but the rate fatigued
      over time and improved after interruption for two ventilations. Those aged 11
      years and older consistently compressed the chest from 31 mm to 50mm. Only one
      participant could successfully ventilate the manikin by mouth-to-mouth.
      CONCLUSION: This study demonstrates that untrained youngsters should perform
      compression-only CPR. From 11 years of age, they can effectively perform
      dispatcher-directed CPR by compressing the chest at an appropriate rate and
      depth. However, their technique benefits from formal training.

PMID- 25779009
TI  - Bactericidal activity of 3 cutaneous/mucosal antiseptic solutions in the presence
      of interfering substances: Improvement of the NF EN 13727 European Standard?
AB  - OBJECTIVE: There is no standard protocol for the evaluation of antiseptics used
      for skin and mucous membranes in the presence of interfering substances. Our
      objective was to suggest trial conditions adapted from the NF EN 13727 standard,
      for the evaluation of antiseptics used in gynecology and dermatology. METHODS:
      Three antiseptic solutions were tested in vitro: a chlorhexidine-benzalkonium
      (CB) combination, a hexamidine-chlorhexidine-chlorocresol (HCC) combination, and
      povidone iodine (P). The adaptation of trial conditions to the standard involved
      choosing dilutions, solvent, and interfering substances. The activity of
      solutions was assessed on the recommended strains at concentrations of 97% (pure
      solution), 50%, and 10% (diluted solution), and 1%. A logarithmic reduction >= 5
      was expected after 60seconds of contact, to meet requirements of bactericidal
      activity. RESULTS: HCC did not present any bactericidal activity except on P.
      aeruginosa at a concentration of 97%. P was not bactericidal on E. hirae at any
      concentration and on S. aureus at 97%. CB had the most homogeneous bactericidal
      activity with a reduction>5 log on the 4 bacterial strains at concentrations of
      97%, 50% and 10%. CONCLUSION: Adapting the NF EN 13727 standard allowed assessing
      the 3 tested solutions: only CB was bactericidal in dirty conditions. This study
      proved the possibility of validating antiseptic choice in vitro, in current
      practice conditions, for adjunctive treatment of skin and mucous membranes
      disorders, primarily of bacterial origin or with a potential of superinfection.

PMID- 25779010
TI  - Molecular characterization of extended spectrum beta-lactamases produced by
      Klebsiella pneumoniae clinical strains from a Tunisian Hospital.
AB  - OBJECTIVES: Extended-spectrum beta-lactamases are widespread in hospital settings
      worldwide. The prevalence of ESBL producing Klebsiella pneumoniae (ESBL-KP)
      strains isolated from patients has recently increased in Tunisia. We conducted
      this study to determine the prevalence and the genetic characterization of ESBL
      KP in a Tunisian Hospital. PATIENTS AND METHODS: We performed antibiotic
      susceptibility testing, multiplex PCR, and DNA sequencing analysis on 118 non
      repetitive K. pneumonia strains isolated during three years, to determine the
      prevalence and genotypes of ESBL among K. pneumoniae clinical isolates. RESULTS:
      Most ESBL-producing K. pneumonia strains were isolated from hospitalized
      patients, especially in neonatal and pediatric wards. The resistance to other
      antibiotics was high. Most of the pathogens were isolated from the urinary tract
      (86.44%). Carbapenems were the most effective antimicrobial agents followed by
      amikacin and fosfomycin. The rate of blaSHV, blaTEM, and blaCTX-M genes among the
      isolates was 89, 56.78, and 81.35%, respectively. Sequencing revealed the
      amplicons encoding TEM-1, TEM-53, TEM-158, SHV-1, SHV-11, SHV-28, CTX-M-15, CTX-M
      15-like. The blaCTX-M-15 was the dominant gene among Tunisian isolates, but this
      was the first report of blaTEM-53 and blaTEM-158 genes in the country.
      CONCLUSIONS: Our results confirm the predominance of CTX-M-15 in Tunisia. To our
      knowledge, this is the first report of TEM-158 and TEM-53 in Tunisia.

PMID- 25779011
TI  - Humoral autoimmune response to nucleophosmin in the immunodiagnosis of
      hepatocellular carcinoma.
AB  - Hepatocellular carcinoma (HCC) is a worldwide prevalent cancer with an exremely
      poor prognosis. Detection of serum alpha-fetoprotein (AFP) and liver imaging
      techniques are the conventional methods used clinically for the identification of
      this malignancy. However, these techniques are not reliable for early diagnosis,
      and particularly the sensitivity and specificity of AFP in HCC diagnosis are not
      optimal. Therefore, there is an urgent need for the development of more sensitive
      and specific methods that can improve AFP quantification in the early detection
      of HCC. In the present study, autoantibody responses to nucleophosmin (NPM1) in
      HCC patients were evaluated by enzyme-linked immunosorbent assay (ELISA), western
      blotting and indirect immunofluorescence. Immunohistochemistry (IHC) with tissue
      array slides was also performed to analyze protein expression of NPM1 in HCC and
      control tissues. The prevalence of autoantibodies against NPM1 was 22.4% (17/76)
      in HCC, which was significantly higher than that in sera from patients with liver
      cirrhosis (LC), chronic hepatitis (CH) and systemic lupus erythematosus (SLE)
      (P<0.01). The average titer of autoantibodies against NPM1 in HCC sera was higher
      compared to that in LC, CH, SLE and normal human sera (NHS) (P<0.01). In
      addition, anti-NMP1 autoantibodies were detected in sera from several HCC
      patients with serial bleeding samples. A stronger reactive band corresponding to
      NMP1 was visualized in the western blot analyses, utilizing sera from patients 3
      6 months before the clinical diagnosis of HCC. Our data indicate that NPM1 and
      the anti-NPM1 system may have potential as an early-stage biomarker for HCC
      screening and diagnosis.

PMID- 25779018
TI  - Comparative analysis of the seminal plasma proteomes of oligoasthenozoospermic
      and normozoospermic men.
AB  - A comparative proteomic study of oligoasthenozoospermic and normozoospermic
      seminal plasmas was conducted to establish differences in protein expression.
      Oligoasthenozoospermia (when semen presents with a low concentration and reduced
      motility of spermatozoa) is common in male infertility. Two-dimensional protein
      maps from seminal plasma samples from 10 men with normozoospermia and 10 men with
      idiopathic oligoasthenozoospermia were obtained by isoelectric focusing followed
      by sodium dodecyl-sulphate polyacrylamide electrophoresis. Map images were
      analysed using dedicated software involving normalization, spot-to-spot volume
      comparison and statistical treatment of the results to establish the significance
      of differences between normal and oligoasthenozoospermic samples. Six out of 1028
      spots showed over 1.5-fold relative intensity differences (P < 0.05, analysis of
      variance). Four proteins were identified by nano liquid chromatography
      electrospray ionization-mass spectrometry/mass spectrometry of their tryptic
      peptides and database searches. Two proteins were more than three-fold under
      expressed in oligoasthenozoospermia, namely epididymal secretory protein E1 and
      galectin-3-binding protein; the other (lipocalin-1 and a prolactin-inducible
      protein form) were over-expressed. The identity and differential expression of
      epididymal secretory protein E1 was verified by Western-blotting. The
      statistically significant differential expression of these four proteins in
      oligoasthenozoospermia compared with normozoospermia provides a molecular basis
      for further investigations into the pathogenic mechanisms underlying idiopathic
      oligoasthenozoospermia. 

PMID- 25779014
TI  - WONOEP appraisal: molecular and cellular imaging in epilepsy.
AB  - Great advancements have been made in understanding the basic mechanisms of
      ictogenesis using single-cell electrophysiology (e.g., patch clamp, sharp
      electrode), large-scale electrophysiology (e.g., electroencephalography [EEG],
      field potential recording), and large-scale imaging (magnetic resonance imaging
      [MRI], positron emission tomography [PET], calcium imaging of acetoxymethyl ester
      [AM] dye-loaded tissue). Until recently, it has been challenging to study
      experimentally how population rhythms emerge from cellular activity. Newly
      developed optical imaging technologies hold promise for bridging this gap by
      making it possible to simultaneously record the many cellular elements that
      comprise a neural circuit. Furthermore, easily accessible genetic technologies
      for targeting expression of fluorescent protein-based indicators make it possible
      to study, in animal models of epilepsy, epileptogenic changes to neural circuits
      over long periods. In this review, we summarize some of the latest imaging tools
      (fluorescent probes, gene delivery methods, and microscopy techniques) that can
      lead to the advancement of cell- and circuit-level understanding of epilepsy,
      which in turn may inform and improve development of next generation antiepileptic
      and antiepileptogenic drugs. 

PMID- 25779019
TI  - Response: adhesion barrier market trends.

PMID- 25779020
TI  - Kit ligand decreases the incidence of apoptosis in cultured vitrified whole mouse
      ovaries.
AB  - To investigate the development of follicles and incidence of apoptosis in
      vitrified cultured mouse ovaries in the presence and absence of Kit ligand, 1
      week-old mouse ovaries were cultured in the presence or absence of Kit ligand for
      7 days. Development and function of ovarian follicles was evaluated by histology
      and hormonal analysis. Apoptosis assessment was conducted by analysis of DNA
      laddering, TdT (terminal deoxynucleotidyl transferase)-mediated dUDP nick-end
      labelling and caspase-3/7 activity. The proportion of preantral follicles and the
      level of 17-beta oestradiol, progesterone and dehydroepiandrosterone were
      increased in all cultured groups, and it was significantly higher in Kit ligand
      treated groups than in the control (P < 0.001). The number of apoptotic signals
      in both vitrified samples is significantly higher than in the non-vitrified
      control (P < 0.01), and these signals are significantly lower in both Kit ligand
      treated groups than in non-Kit ligand treated groups (P < 0.001). The level of
      caspase-3/7 activity was higher in vitrified cultured ovaries than non-vitrified
      group (P < 0.01). Kit ligand was shown to improve in-vitro development of
      follicles, and also acted as an anti-apoptotic factor in vitrified ovaries. The
      developmental potential of follicles in vitrified groups was lower than that in
      fresh ovaries. 

PMID- 25779021
TI  - A prospective study using Hatha Yoga for stress reduction among women waiting for
      IVF treatment.
AB  - Yoga has been found to be effective in treating anxiety and depression, reducing
      stress and improving the overall quality of life in the general population.
      Minimal research is available on the effect of stress-management programmes with
      IVF patients. Owing to the diversity of conditions treated, the poor quality of
      most studies, and the different assessment tools used to evaluate the
      psychological state, it is difficult to draw definite conclusions. Previous
      studies have used different mind-body interventions and general measures of
      stress without evaluation of specific stresses known to result from infertility
      and its treatment using standardized measures. In this single-centre study, 49
      infertile women were recruited to participate in a 6-week Yoga class during 2013
      while awaiting their IVF treatment. Study participants were asked to complete
      standardized questionnaires assessing fertility-related quality of life
      (FertiQoL), marital harmony (Dyadic Adjustment Scale [DAS]), state and trait
      anxiety (State-Trait Anxiety Inventory [STAI]) and depression (Beck Depression
      Inventory [BDI]) before commencing and after completing the Yoga workshops.
      Anxiety, depression and fertility-specific quality of life showed improvement
      over time in association with participation in a 6-week Yoga programme in women
      awaiting their treatment with IVF. 

PMID- 25779022
TI  - Variation in pediatric emergency department care of sickle cell disease and
      fever.
AB  - OBJECTIVES: The objective was to study the variation in pediatric emergency
      department (PED) practice patterns for evaluation and management of children with
      sickle cell disease (SCD) and fever in U.S. children's hospitals. METHODS: A
      cross-sectional study of visits by children 3 months to 18 years of age with SCD
      and fever evaluated in 36 U.S. children's hospital PEDs within the 2010 Pediatric
      Health Information System database. The main outcome measures were the
      proportions of SCD visits that received evaluation (laboratory testing and chest
      radiographs [CXRs]) and treatment (parenteral administration of antibiotics) and
      were admitted for fever. RESULTS: Of the 4,853 PED visits for SCD and fever,
      91.7% had complete blood counts (CBCs), 93.8% had reticulocyte counts, 93% had
      blood cultures obtained, 68.5% had CXRs, and 91.7% received antibiotics. Most
      (81.4%) patients received the recommended National Heart, Lung and Blood
      Institute evaluation (CBC, reticulocyte count, and blood culture) and treatment
      (parenteral antibiotics). In multivariate regression modeling controlling for
      hospital- and patient-level effects, age groups >=1 to <5 years (odds ratio [OR]
      = 0.32, 95% confidence interval [CI] = 0.25 to 0.40) and >=5 to <13 years (OR =
      0.40, 95% CI = 0.32 to 0.50), and those visits that did not have CXRs had lower
      odds of hospital admission. After adjusting for age, payor status, receipt of
      laboratory testing, antibiotics, and CXRs, admission rates varied by sevenfold
      across U.S. children's hospitals (p < 0.001). CONCLUSIONS: Standardization of
      practice exists across children's hospitals regarding obtaining laboratory
      studies and administering antibiotics for patients with SCD and fever. However,
      admission rates vary significantly. Evaluating the causes and consequences of
      such significant variation needs further exploration to improve the quality of
      care for patients with SCD.

PMID- 25779023
TI  - Evaluation of different real time PCRs for the detection of Pneumocystis
      jirovecii DNA in formalin-fixed paraffin-embedded bronchoalveolar lavage samples.
AB  - The presence of Pneumocystis jirovecii in fresh clinical materials can be
      detected by PCR with high sensitivity and is thus preferred over microscopic
      methods. However, fresh materials are not always available, and on formalin-fixed
      paraffin-embedded materials, PCR may result in reduced detection rates. In this
      study the diagnostic sensitivity of P. jirovecii real time PCR on DNA isolated
      from fresh bronchoalveolar lavage (BAL) samples versus that from matched FFPE
      derived DNA is analyzed. Our results indicate that when targeting a small DNA
      fragment P. jirovecii PCR can be performed on FFPE BAL samples with acceptable
      sensitivity (up to 83.3%). This is considerably higher than the 33.3% positives
      observed by classical staining of these samples. 

PMID- 25779024
TI  - Linking the ceramide synthases (CerSs) 4 and 5 with apoptosis, endometrial and
      colon cancers.
AB  - Ceramide synthases (CerSs) also known as Longevity Assurance (LASS) genes belong
      to a family of six related genes. CerS gene products have been shown to produce
      ceramide, hence their name CerSs. Ceramide is a bio-effector molecule, belonging
      to the family of sphingolipids (SLs), which are important components of cell
      membranes, and has been implicated in cancer and apoptosis. Cancer still remains
      the second leading cause of death, both globally and in South Africa. The proper
      regulation of the balance between cell growth and cell death is essential for
      cellular homeostasis. Failure to properly regulate this balance may lead to
      pathologic conditions such as cancer development. CerSs have been implicated in
      cancer biology, especially in apoptosis, through the action of ceramide. Although
      knowledge of the role that CerSs play in cancer biology is advancing, the precise
      roles of distinct CerSs in different cancers are not yet fully understood,
      especially the roles of CerS4 and CerS5 in endometrial and colon cancers. The aim
      of this study was to investigate the link of CerS4 and CerS5 in apoptosis and,
      thus in cancers of the endometrium and colon, which are amongst the most
      prevalent cancers globally. Apoptosis was induced using anastrozole in
      endometrial cells and 5-FU in colon cells. Fluorescence activated cell sorting
      was used to analyse and quantify apoptosis and total RNA was extracted from both
      treated and untreated cells. Quantitative relative expression of CerS4 and CerS5
      mRNA was then determined in all cells (treated and untreated), normalised to beta
      actin. Bio-informatics was used to compare CerS4 and CerS5 sequences. The
      endometrial cancer cells were more prone to apoptosis compared to their non
      cancerous counterparts, while the colon cancer cells were more responsive to
      apoptosis induction after 48h, especially the HT-29 cells. Using quantitative
      real-time PCR, both CerS4 and CerS5 were shown to be up-regulated in endometrial
      and colon cancer cells. Apoptosis induction resulted in down-regulation of CerS4
      and CerS5 in endometrial and colon cancers. These findings implicate these genes
      in cancer and apoptosis. Whether these genes play pro- or anti-apoptotic roles in
      cancers of the endometrium and colon is not conclusive at this stage. It may also
      be possible that these genes could exert opposing roles in the same or different
      tissues. Targeting this family of genes and understanding their precise
      individual roles in different types of cancer, are a promising therapeutic tool
      to new anti-cancer drug discovery or improving existing treatments. 

PMID- 25779026
TI  - Identifying acute kidney injury in the community--a novel informatics approach.
AB  - BACKGROUND: Acute kidney injury (AKI) is a serious and common problem that is
      associated with high mortality. Currently nearly all efforts at improving
      outcomes in AKI have been focused on secondary care. We now know that a large
      number of patients most likely develop the condition in primary care. To our
      knowledge there has been no previous attempts to approach this topic from the
      primary care perspective. AIM: To test the utility of novel informatics software
      to identify patients with AKI in the community. SETTING AND METHOD: We carried
      out a retrospective audit of patients in one urban practice in Leicestershire
      using novel informatics software. The audit data was run on two occasions, once
      for high-risk patients between 4th July 2010 through until 30th September 2013,
      and once for low risk patients for the period of 27th October 2011 through until
      21st January 2014. RESULTS: During the period of the data collection the average
      practice list size was 12,420, with 235 and 19 AKI episodes in the high and low
      risk groups respectively. The annual AKI incidence was 27.9/1000 in the high-risk
      group, 1.22/1000 in the low risk group, and 10.6/1000 overall. The most common
      associated factor was sepsis in 170 patients, followed by dehydration in 54
      patients. CONCLUSION: We have shown it is possible to identify patients with AKI
      in the community using informatics software. Our data suggests that AKI in the
      community is much more common than previously thought and demonstrates the need
      to better understand this condition from the primary care perspective.

PMID- 25779025
TI  - Combination of electroacupuncture and grafted mesenchymal stem cells
      overexpressing TrkC improves remyelination and function in demyelinated spinal
      cord of rats.
AB  - This study attempted to graft neurotrophin-3 (NT-3) receptor (TrkC) gene modified
      mesenchymal stem cells (TrkC-MSCs) into the demyelinated spinal cord and to
      investigate whether electroacupuncture (EA) treatment could promote NT-3
      secretion in the demyelinated spinal cord as well as further enhance grafted TrkC
      MSCs to differentiate into oligodendrocytes, remyelination and functional
      recovery. Ethidium bromide (EB) was microinjected into the spinal cord of rats at
      T10 to establish a demyelinated model. Six groups of animals were prepared for
      the experiment: the sham, PBS, MSCs, MSCs+EA, TrkC-MSCs and TrkC-MSCs+EA groups.
      The results showed that TrkC-MSCs graft combined with EA treatment (TrkC-MSCs+EA
      group) significantly increased the number of OPCs and oligodendrocyte-like cells
      differentiated from MSCs. Immunoelectron microscopy showed that the
      oligodendrocyte-like cells differentiated from TrkC-MSCs formed myelin sheaths.
      Immunofluorescence histochemistry and Western blot analysis indicated that TrkC
      MSCs+EA treatment could promote the myelin basic protein (MBP) expression and
      Kv1.2 arrangement trending towards the normal level. Furthermore, behavioural
      test and cortical motor evoked potentials detection demonstrated a significant
      functional recovery in the TrkC-MSCs+EA group. In conclusion, our results suggest
      that EA treatment can increase NT-3 expression, promote oligodendrocyte-like cell
      differentiation from TrkC-MSCs, remyelination and functional improvement of
      demyelinated spinal cord.

PMID- 25779027
TI  - Role of EFNB1 and EFNB2 in Mouse Collagen-Induced Arthritis and Human Rheumatoid
      Arthritis.
AB  - OBJECTIVE: EFNB1 and EFNB2 are ligands for Eph receptor tyrosine kinases. This
      study was undertaken to investigate how the expression of Efnb1 and Efnb2 on
      murine T cells influences the pathogenesis of collagen-induced arthritis (CIA)
      and to assess correlations between the T cell expression of these 2 molecules and
      measures of disease activity in patients with rheumatoid arthritis (RA). METHODS:
      CIA was studied in mice with T cell-specific deletion (double gene knockout
      [dKO]) of both Efnb1 and Efnb2. Expression of EFNB1 and EFNB2 messenger RNA
      (mRNA) in peripheral blood T cells from patients with RA was determined by
      quantitative reverse transcription- polymerase chain reaction. RESULTS: In dKO
      mice, clinical scores of arthritis were reduced compared to those in wild-type
      (WT) control mice. Serum collagen-specific antibody titers in dKO mice were lower
      than those in WT mice. In analyses based on equal cell numbers, dKO mouse T
      cells, as compared to WT mouse T cells, provided vastly inferior help to B cells
      in the production of collagen-specific antibodies in vitro. T cells from dKO mice
      were compromised in their ability to migrate to the arthritic paws in vivo and in
      their ability to undergo chemotaxis toward CXCL12 in vitro. Deletion mutation of
      Efnb1 and Efnb2 intracellular tails revealed critical regions in controlling T
      cell chemotaxis. T cells from RA patients expressed higher EFNB1 mRNA levels,
      which correlated with RA symptoms and laboratory findings. CONCLUSION: Efnb1 and
      Efnb2 in T cells are essential for pathogenic antibody production and for T cell
      migration to the inflamed paws in mice with CIA. These findings suggest that the
      expression of EFNB1 in T cells might be a useful parameter for monitoring RA
      disease activity and treatment responses.

PMID- 25779028
TI  - The visualisation of clinical leadership in the content of nursing education--a
      qualitative study of nursing students' experiences.
AB  - OBJECTIVE: The aim of this study was to describe nursing students' experiences of
      clinical leadership during their last year of education. BACKGROUND: Work as a
      nurse is complex with several demands from stakeholders who are colleagues,
      managers, patients and relatives. Therefore, it is important to provide students
      with tools for a forthcoming professional life as a nurse. SETTING, PARTICIPANTS
      AND METHOD: A qualitative descriptive study was carried out in Jordan. Narratives
      (n=20) written by nursing students in their last year before graduation as a
      registered nurse were collected. The data were analysed by a manifest content
      analysis. RESULTS: The results formed one category: (Clinical leadership-safety
      in being a nurse), and three subcategories (eye-opener, a role model and bridging
      the gap) described the students' clinical leadership experiences due to the
      preparation process for being a nurse. Clinical leadership applies theory to
      practice by using a holistic view in nursing. CONCLUSION: Clinical leadership is
      a valuable tool for bridging the gap between theory and practice in nursing
      education. Skills within nursing management clarify and simplify nursing
      activities, which facilitates the transition from student to nurse. Focus on
      learning needs in nursing management is needed for stakeholders within education
      and health care organisations to facilitate graduation of well skilled nurses.

PMID- 25779029
TI  - Nurses' competence in pain management in patients with opioid addiction: A cross
      sectional survey study.
AB  - BACKGROUND: There may be up to 21 million opioid abusers in the world. Drug abuse
      and associated health-related problems are increasing. Opioid addiction can cause
      serious bacterial infection, injury and trauma, conditions that can trigger pain.
      Opioid abusers experience pain differently from non-addicts. There is limited
      research on nurses' competence to provide pain treatment to patients with opioid
      addiction. OBJECTIVE: To report on a Norwegian pilot study examining nurses'
      knowledge about pain and competence in treating pain in patients who abuse
      opioids. DESIGN: A descriptive cross-sectional survey design was employed.
      PARTICIPANTS: Nurses at medical (n=64) and orthopaedic (n=34) units at two urban,
      public Norwegian hospitals. METHODS: Data were collected in January 2010 using a
      self-administered questionnaire. Sample selection was determined by purposive
      sampling. The response rate was 54%. RESULTS: Eighty-eight percent of nurses did
      not have sufficient knowledge about pain treatment in patients with opioid
      addiction. Eight-eight percent and seventy-seven percent regarded work-place
      experience and colleagues as the primary contributors to their knowledge about
      pain treatment, respectively. Work-place experience contributed most to nurses'
      competence. Ninety percent, 70% and 84% of nurses responded that education,
      literature and information technology, respectively, played a minor role in
      obtaining knowledge about pain management. Sixty-five percent of the respondents
      had basic skills for evaluating pain, although 54% could not evaluate the degree
      of pain. Almost 62% of nurses did not trust the pain experience self-reported by
      patients who were opioid abusers. CONCLUSION: Our study shows shortcomings in the
      nurses' competence to evaluate and treat pain, suggesting that patients with
      opioid addiction may not receive adequate pain management. Nurses' competence to
      offer pain treatment to opioid abusers could be characterized as experience-based
      rather than evidence-based.

PMID- 25779030
TI  - The role of apoptosis in human embryo implantation.
AB  - The process of embryo attachment and invasion through the endometrial epithelial
      cells and subsequent implantation into the decidualized endometrial stroma is the
      groundbreaking step for the establishment of a successful pregnancy. Necessary
      prerequisites are a receptive endometrium, a good-quality embryo and a well
      orchestrated molecular dialog between embryo and maternal endometrium. The embryo
      maternal dialog is conducted via a wide scope of factors, including secreted
      cytokines, chemokines, and growth factors in addition to the expression of
      corresponding receptors and co-receptors. Several embryonic proteins, including
      the aforementioned, are involved in the process of apoptosis, which necessarily
      needs to take place at the maternal endometrium to allow the embryo to invade.
      The endometrial epithelium is thereby disintegrated completely within a
      particular area, whereas the endometrial stroma seems to require a more depth
      limited apoptosis. As of today, the exact mechanisms and factors mediating the
      apoptotic process involved in those apparently differently regulated incidents
      are not fully understood, particularly with regard to stromal cell apoptosis.
      There is evidence though, that cytokines and their respective receptors play a
      major role. A suggested important co-receptor for cytokines, which is highly
      upregulated in the receptive human endometrium, is the heparan sulfate
      proteoglycan syndecan-1. It is present on the cell surface and involved in the
      regulation of cell-cell-interaction, cell binding, cell signaling and
      cytoskeletal organization and therefore represents a possible mediator of
      apoptosis regulation in human endometrium. Herein, the literature on endometrial
      epithelial and stromal apoptosis in general, and in light of the influence of
      syndecan-1, is reviewed. 

PMID- 25779031
TI  - Co-expression of functional human Heme Oxygenase 1, Ecto-5'-Nucleotidase and ecto
      nucleoside triphosphate diphosphohydrolase-1 by "self-cleaving" 2A peptide
      system.
AB  - We developed an F2A-based multicistronic system to evaluate functional effects of
      co-expression of three proteins important for xenotransplantation: heme oxygenase
      1 (HO1), ecto-5'-nucleotidase (E5NT) and ecto-nucleoside triphosphate
      diphosphohydrolase-1 (ENTPD1). The tricistronic p2A plasmid that we constructed
      was able to efficiently drive concurrent expression of HO1, E5NT and ENTPD1 in
      HEK293T cells. All three overexpressed proteins possessed relevant enzymatic
      activities, while addition of furin site interfered with protein expression and
      activity. We conclude that our tricistronic p2A construct is effective and
      optimal to test the combined protective effects of HO1, E5NT and ENTPD1 against
      xeno-rejection mechanisms. 

PMID- 25779032
TI  - The effects of beta-arrestin1 deletion on acute cannabinoid activity, brain
      cannabinoid receptors and tolerance to cannabinoids in mice.
AB  - CONTEXT: Previous studies have indicated a role for beta-arrestin2 in the
      regulation of brain cannabinoid effects and cannabinoid CB1 receptors, but
      whether beta-arrestin1 has a role has not been investigated. OBJECTIVE: To
      determine the role of beta-arrestin1 in cannabinoid activity. MATERIALS AND
      METHODS: Beta-arrestin1 -/- mice and their wild-type (+/+) counterparts were
      assayed for antinociceptive and temperature-decreasing effects of two ligands,
      Delta(9)-tetrahydrocannabinol (THC) and CP55940, after both single and repeated
      administration. In vitro assays examined the effects of deletion on CB1 receptor
      density, agonist-binding and G-protein activation. RESULTS: Deletion of beta
      arrestin1 diminished the effects of CP55940 in both antinociception (latency to
      tail withdrawal) and temperature-depression assays in mice. However, deleting
      beta-arrestin1 had no effect on the actions of THC in either assay. Antagonist
      radioligand ([(3)H]SR141716A) saturation binding indicated no difference between
      beta-arrestin1 +/+ and -/- mice in the density or affinity for cannabinoid CB1
      receptors in brain membranes. CP55940 agonist binding in brain membranes from
      beta-arrestin1 +/+ mice exhibited high- and intermediate-affinity sites, but beta
      arrestin1 -/- membranes exhibited an additional site with low affinity. CP55940
      produced greater stimulation of [(35)S]GTPgammaS binding to membranes from whole
      brain of beta-arrestin1 -/- than +/+ mice. The rates of the development of
      tolerance to chronic THC or CP55940 administration did not appear to be affected
      by genotype. DISCUSSION: Beta-arrestin1 appeared to mediate the actions of
      CP55940, but did not affect the activity of THC. CONCLUSION: Beta-arrestin1
      regulates cannabinoid CB1 receptor sensitivity in an agonist-selective manner,
      but may not be the primary mediator of tolerance to cannabinoid agonists.

PMID- 25779033
TI  - White matter fractional anisotropy over two time points in early onset
      schizophrenia and adolescent cannabis use disorder: A naturalistic diffusion
      tensor imaging study.
AB  - Recurrent exposure to cannabis in adolescence increases the risk for later
      development of psychosis, but there are sparse data regarding the impact of
      cannabis use on brain structure during adolescence. This pilot study investigated
      the effect of cannabis use disorder (CUD) upon white matter fractional anisotropy
      (WM FA) values in non-psychotic treatment-seeking adolescents relative to
      adolescents with early onset schizophrenia-spectrum disorders (EOSS) and to
      healthy control (HC) participants. Diffusion tensor imaging (DTI) and
      tractography methods were used to examine fractional anisotropy (FA) of the
      cingulum bundle, superior longitudinal fasciculus (SLF), corticospinal tract
      (CST), inferior longitudinal fasciculus (ILF), inferior fronto-occipital
      fasciculus (IFOF) and uncinate fasciculus in adolescents with EOSS (n=34), CUD
      (n=19) and HC (n=29). Participants received DTI and substance use assessments at
      baseline and at 18-month follow-up. Using multivariate analysis of variance, a
      significant main effect of diagnostic group was observed. Post-hoc testing
      revealed that adolescents with CUD showed an altered change in FA values in the
      left ILF and in the left IFOF (trend level) compared with HC adolescents. Greater
      consumption of cannabis during the inter-scan interval predicted a greater
      decrease in left ILF FA in CUD. These preliminary longitudinal data suggest that
      heavy cannabis use during adolescence, or some factor associated with cannabis
      use, is associated with an altered change in WM FA values in a fiber bundle that
      has been implicated in the pathophysiology of EOSS (i.e., the left ILF).
      Additional studies are needed to clarify the clinical significance of these
      findings. 

PMID- 25779035
TI  - Berkson's paradox in medical care.

PMID- 25779034
TI  - Widespread white matter tract aberrations in youth with familial risk for bipolar
      disorder.
AB  - Few studies have examined multiple measures of white matter (WM) differences in
      youth with familial risk for bipolar disorder (FR-BD). To investigate WM in the
      FR-BD group, we used three measures of WM structure and two methods of analysis.
      We used fractional anisotropy (FA), axial diffusivity (AD), and radial
      diffusivity (RD) to analyze diffusion tensor imaging (DTI) findings in 25 youth
      with familial risk for bipolar disorder, defined as having both a parent with BD
      and mood dysregulation, and 16 sex-, age-, and IQ-matched healthy controls. We
      conducted a whole brain voxelwise analysis using tract based spatial statistics
      (TBSS). Subsequently, we conducted a complementary atlas-based, region-of
      interest analysis using Diffeomap to confirm results seen in TBSS. When TBSS was
      used, significant widespread between-group differences were found showing
      increased FA, increased AD, and decreased RD in the FR-BD group in the bilateral
      uncinate fasciculus, cingulum, cingulate, superior fronto-occipital fasciculus
      (SFOF), superior longitudinal fasciculus (SLF), inferior longitudinal fasciculus,
      and corpus callosum. Atlas-based analysis confirmed significant between-group
      differences, with increased FA and decreased RD in the FR-BD group in the SLF,
      cingulum, and SFOF. We found significant widespread WM tract aberrations in youth
      with familial risk for BD using two complementary methods of DTI analysis. 

PMID- 25779036
TI  - Synthesis of [(18)F]FMISO in a flow-through microfluidic reactor: Development and
      clinical application.
AB  - INTRODUCTION: The PET radiotracer [(18)F]FMISO has been used in the clinic to
      image hypoxia in tumors. The aim of the present study was to optimize the
      radiochemical parameters for the preparation of [(18)F]FMISO using a microfluidic
      reaction system. The main parameters evaluated were (1) precursor concentration,
      (2) reaction temperature, and (3) flow rate through the microfluidic reactor.
      Optimized conditions were then applied to the batch production of [(18)F]FMISO
      for clinical research use. METHODS: For the determination of optimal reaction
      conditions within a flow-through microreactor synthesizer, 5-400 MUL the
      precursor and dried [(18)F]fluoride solutions in acetonitrile were simultaneously
      pushed through the temperature-controlled reactor (60-180  degrees C) with
      defined flow rates (20-120 MUL/min). Radiochemical incorporation yields to form
      the intermediate species were determined using radio-TLC. Hydrolysis to remove
      the protecting group was performed following standard vial chemistry to afford
      [(18)F]FMISO. RESULTS: Optimum reaction parameters for the microfluidic set-up
      were determined as follows: 4 mg/mL of precursor, 170  degrees C, and 100 MUL/min
      pump rate per reactant (200 MUL/min reaction overall flow rate) to prepare the
      radiolabeled intermediate. The optimum hydrolysis condition was determined to be
      2N HCl for 5 min at 100  degrees C. Large-scale batch production using the
      optimized conditions gave the final, ready for human injection [(18)F]FMISO
      product in 28.4 +/- 3.0% radiochemical yield, specific activity of 119 +/- 26
      GBq/MUmol, and >99% radiochemical and chemical purity at the end of synthesis (n
      = 4). CONCLUSION: By using the NanoTek microfluidic synthesis system,
      [(18)F]FMISO was successfully prepared with good specific activity and high
      radiochemical purity for human use. The product generated from large-scale batch
      production using flow chemistry is currently being used in clinical research.

PMID- 25779037
TI  - A novel multivalent (99m)Tc-labeled EG2-C4bpalpha antibody for targeting the
      epidermal growth factor receptor in tumor xenografts.
AB  - INTRODUCTION: The C4b binding protein (C4bp) alpha/beta-chain C-terminal
      effectively induces polymerization during protein synthesis. Using this fragment
      and the single-domain antibody EG2, which targets the epidermal growth factor
      receptor (EGFR), we generated the novel multimeric antibody EG2-C4bpalpha. We
      radiolabeled EG2-C4bpalpha with (99m)Tc and evaluated its targeting efficiency
      and pharmacokinetics in tumor xenografts. METHODS: EGFR expression and EGFR-EG2
      C4bpalpha binding was evaluated in A431 and OCM-1 cells by Western blotting and
      flow cytometry, respectively. EG2-C4bpalpha was radiolabeled with
      [(99m)Tc(CO)3(OH2)3](+) using a tricarbonyl vial followed by purification on a PD
      10 column. In vitro studies with (99m)Tc-EG2-C4bpalpha were performed in A431
      and/or OCM-1 cells. Single photon emission computed tomography (SPECT) imaging
      and biodistribution studies were carried out in (99m)Tc-EG2-C4bpalpha-injected
      mice bearing A431- and OCM-1-derived tumors. EGFR immunofluorescent staining in
      A431 and OCM-1 tumors was performed. RESULTS: A431 cells showed higher EGFR
      expression levels than OCM-1 cells, and flow cytometry confirmed EG2-C4bpalpha
      bound more A431 cells than OCM-1 cells. (99m)Tc-EG2-C4bpalpha was successfully
      prepared with radiochemical yields of 30.3-50.4%. The binding affinity of (99m)Tc
      EG2-C4bpalpha to A431 cells was approximately 20 nM. (99m)Tc-EG2-C4bpalpha
      specifically bound A431 cells and this binding was blocked by 41% in the presence
      of 50 nM excess unlabeled EG2-C4bpalpha. In vivo radioactivity uptake in A431
      tumors was detected 2h after (99m)Tc-EG2-C4bpalpha administration and sustained
      up to 18h. The highest ratio of A431 tumor-to-muscle and tumor-to-blood was 3.69
      +/- 0.48 at 10h and 0.77 +/- 0.14 at 20 h, respectively. Excess unlabeled EG2
      C4bpalpha blocked radioactivity uptake in A431 tumors by 55% at 10h. (99m)Tc-EG2
      C4bpalpha was barely detectable in OCM-1 tumors, and biodistribution analysis
      confirmed that radioactivity uptake was significantly lower than in A431 tumors.
      CONCLUSIONS: (99m)Tc-EG2-C4bpalpha specifically and efficiently targets EGFR over
      expressing tumors suggesting that EG2-C4bpalpha may be a promising antibody
      alternative for future diagnostic application and potential radioimmunotherapy.
      However, the high activity in the blood and liver, and the relative low ratio of
      tumor-to-blood should be noticed and improved.

PMID- 25779039
TI  - Recombinant osteopontin attenuates experimental cerebral vasospasm following
      subarachnoid hemorrhage in rats through an anti-apoptotic mechanism.
AB  - Cerebral vasospasm (CVS) is an important pathological process following
      subarachnoid hemorrhage (SAH). Osteopontin (OPN), a pleiotropic extracellular
      glycoprotein, has been reported to be able to induce MKP-1 in the spastic
      cerebral arteries and prevent vasospasm after SAH. The purpose of this study was
      to investigate the protective effects of recombinant OPN (r-OPN) on CVS following
      SAH and the underlying mechanisms associated with its anti-apoptotic effect.
      Eighty male Sprague Dawley rats (weighing 300-375g) were randomly assigned to
      four groups: (1) sham+vehicle (n=20), (2) SAH+vehicle (n=20), (3) SAH+OPN0.03
      (0.03MUg) (n=20), (4) SAH+OPN0.1 (0.1MUg) (n=20). The double injection model of
      cisterna magna was performed on day 0 and 48h after the first induction. r-OPN
      was administered intraventricularly nearly 30min after the first SAH. After
      neurological score assessment, rats were sacrificed 72h after the first SAH. The
      cross-sectional area and thickness of basilar arteries (BA) were measured under
      Hematoxylin-eosin (H&E) staining. Endothelial cell apoptosis was identified by
      terminal deoxynucleotidyl transferase mediated nick end labeling (TUNEL)
      staining. Immunohistochemistry was used to assess the expression of p-Akt and
      cleaved caspase-3 in BA. Western blot analysis was applied to evaluate the
      expression of p-Akt, cleaved caspase-3, Bax and Bcl-2 in BA. r-OPN improved
      neurological scores and attenuated vasospasm. r-OPN significantly reduced
      expression of cleaved caspase-3 and Bax in BA following SAH, and increased the
      level of p-Akt and Bcl-2, coupled with reduced apoptosis of endothelial cell in
      BA. These results demonstrate that r-OPN can attenuate vasospasm after SAH
      through a suppressed apoptotic response, which may provide a novel therapeutic
      target for cerebral vasospasm. 

PMID- 25779038
TI  - Stress-activated afferent inputs into the anterior parvicellular part of the
      paraventricular nucleus of the hypothalamus: Insights into urocortin 3 neuron
      activation.
AB  - Urocortin 3 (Ucn 3) is a member of the corticotropin-releasing factor family,
      which plays a major role in coordinating stress responses. Ucn 3 neurons in the
      anterior parvicellular part of the paraventricular nucleus of the hypothalamus
      (PVHap) provide prominent input into the ventromedial nucleus of the hypothalamus
      (VMH), a well known satiety center, where Ucn 3 acts to suppress feeding and
      modulate blood glucose levels. In the present study, we first determined that Ucn
      3 expression in the PVHap was stimulated by acute restraint stress. We then
      performed retrograde tracing with fluorogold (FG) combined with
      immunohistochemistry for Fos as a marker for neuronal activation after restraint
      stress to determine the stress-activated afferent inputs into the PVHap.
      Substantial numbers of FG/Fos double labeled cells were found in the bed nucleus
      of the stria terminalis, the lateral septal nucleus, the medial amygdala, and a
      number of nuclei in the hypothalamus including the VMH, the arcuate nucleus, the
      posterior nucleus, and the ventral premammillary nucleus. In the brainstem,
      FG/Fos positive cells were found in the periaqueductal gray, the nucleus of the
      solitary tract, and the ventrolateral medulla. In conclusion, the present study
      showed that acute stress rapidly stimulates Ucn 3 expression in the PVHap and
      identified specific stress-sensitive brain areas that project to the PVHap. These
      areas are potentially important in mediating the stress-induced activation of Ucn
      3 neurons in the PVHap. 

PMID- 25779040
TI  - Excitotoxicity induced by kainic acid provokes glycogen synthase kinase-3
      truncation in the hippocampus.
AB  - In neuronal cultures, glycogen synthase kinase 3(GSK3) is truncated at the N
      terminal end by calpain downstream of activated glutamate receptors. However, the
      in vivo biological significance of that truncation has not been explored. In an
      attempt to elucidate if GSK3 truncation has a pathophysiological relevance, we
      have used intraperitoneal injections of kainic acid (KA) in rats and intra
      amygdala KA microinjections in mice as in vivo models of excitotoxicity. Spectrin
      cleavage analyzed by immunohistochemistry was observed in the CA1 hippocampal
      field in KA-intraperitoneal treated rats while the CA3 region was the hippocampal
      area affected after intra-amygdala KA microinjections. GSK3beta
      immunofluorescence did not colocalize with truncated spectrin in both treatments
      using an antibody that recognize the N-terminal end of GSK3beta. Thus, those
      neurons which are spectrin-positive do not show GSK3beta immunolabelling. To
      study GSK3beta truncation in vitro, we exposed organotypic hippocampal slices and
      cultured cortical neurons to KA leading to the truncation of GSK3 and we found
      that truncation was blocked by the calpain inhibitor calpeptin. These data
      suggest a relationship between N-terminal GSK3beta truncation and excitotoxicity.
      Overall, our data reinforces the important relationship between glutamate
      receptors and GSK3 and their role in neurodegenerative processes in which
      excitotoxicity is involved. 

PMID- 25779041
TI  - Dumbbell-PCR: a method to quantify specific small RNA variants with a single
      nucleotide resolution at terminal sequences.
AB  - Recent advances in next-generation sequencing technologies have revealed that
      cellular functional RNAs are not always expressed as single entities with fixed
      terminal sequences but as multiple isoforms bearing complex heterogeneity in both
      length and terminal sequences, such as isomiRs, the isoforms of microRNAs.
      Unraveling the biogenesis and biological significance of heterogenetic RNA
      expression requires distinctive analysis of each RNA variant. Here, we report the
      development of dumbbell PCR (Db-PCR), an efficient and convenient method to
      distinctively quantify a specific individual small RNA variant. In Db-PCR, 5'-
      and 3'-stem-loop adapters are specifically hybridized and ligated to the 5'- and
      3'-ends of target RNAs, respectively, by T4 RNA ligase 2 (Rnl2). The resultant
      ligation products with 'dumbbell-like' structures are subsequently quantified by
      TaqMan RT-PCR. We confirmed that high specificity of Rnl2 ligation and TaqMan RT
      PCR toward target RNAs assured both 5'- and 3'-terminal sequences of target RNAs
      with single nucleotide resolution so that Db-PCR specifically detected target
      RNAs but not their corresponding terminal variants. Db-PCR had broad
      applicability for the quantification of various small RNAs in different cell
      types, and the results were consistent with those from other quantification
      method. Therefore, Db-PCR provides a much-needed simple method for analyzing RNA
      terminal heterogeneity. 

PMID- 25779042
TI  - Identification of U2AF(35)-dependent exons by RNA-Seq reveals a link between 3'
      splice-site organization and activity of U2AF-related proteins.
AB  - The auxiliary factor of U2 small nuclear RNA (U2AF) is a heterodimer consisting
      of 65- and 35-kD proteins that bind the polypyrimidine tract (PPT) and AG
      dinucleotides at the 3' splice site (3'ss). The gene encoding U2AF35 (U2AF1) is
      alternatively spliced, giving rise to two isoforms U2AF35a and U2AF35b. Here, we
      knocked down U2AF35 and each isoform and characterized transcriptomes of HEK293
      cells with varying U2AF35/U2AF65 and U2AF35a/b ratios. Depletion of both isoforms
      preferentially modified alternative RNA processing events without widespread
      failure to recognize 3'ss or constitutive exons. Over a third of differentially
      used exons were terminal, resulting largely from the use of known alternative
      polyadenylation (APA) sites. Intronic APA sites activated in depleted cultures
      were mostly proximal whereas tandem 3'UTR APA was biased toward distal sites.
      Exons upregulated in depleted cells were preceded by longer AG exclusion zones
      and PPTs than downregulated or control exons and were largely activated by PUF60
      and repressed by CAPERalpha. The U2AF(35) repression and activation was
      associated with a significant interchange in the average probabilities to form
      single-stranded RNA in the optimal PPT and branch site locations and sequences
      further upstream. Although most differentially used exons were responsive to both
      U2AF subunits and their inclusion correlated with U2AF levels, a small number of
      transcripts exhibited distinct responses to U2AF35a and U2AF35b, supporting the
      existence of isoform-specific interactions. These results provide new insights
      into function of U2AF and U2AF35 in alternative RNA processing. 

PMID- 25779043
TI  - Quantitative analysis of single-molecule force spectroscopy on folded chromatin
      fibers.
AB  - Single-molecule techniques allow for picoNewton manipulation and nanometer
      accuracy measurements of single chromatin fibers. However, the complexity of the
      data, the heterogeneity of the composition of individual fibers and the
      relatively large fluctuations in extension of the fibers complicate a structural
      interpretation of such force-extension curves. Here we introduce a statistical
      mechanics model that quantitatively describes the extension of individual fibers
      in response to force on a per nucleosome basis. Four nucleosome conformations can
      be distinguished when pulling a chromatin fiber apart. A novel, transient
      conformation is introduced that coexists with single wrapped nucleosomes between
      3 and 7 pN. Comparison of force-extension curves between single nucleosomes and
      chromatin fibers shows that embedding nucleosomes in a fiber stabilizes the
      nucleosome by 10 kBT. Chromatin fibers with 20- and 50-bp linker DNA follow a
      different unfolding pathway. These results have implications for accessibility of
      DNA in fully folded and partially unwrapped chromatin fibers and are vital for
      understanding force unfolding experiments on nucleosome arrays. 

PMID- 25779044
TI  - DAP5 associates with eIF2beta and eIF4AI to promote Internal Ribosome Entry Site
      driven translation.
AB  - Initiation is a highly regulated rate-limiting step of mRNA translation. During
      cap-dependent translation, the cap-binding protein eIF4E recruits the mRNA to the
      ribosome. Specific elements in the 5'UTR of some mRNAs referred to as Internal
      Ribosome Entry Sites (IRESes) allow direct association of the mRNA with the
      ribosome without the requirement for eIF4E. Cap-independent initiation permits
      translation of a subset of cellular and viral mRNAs under conditions wherein cap
      dependent translation is inhibited, such as stress, mitosis and viral infection.
      DAP5 is an eIF4G homolog that has been proposed to regulate both cap-dependent
      and cap-independent translation. Herein, we demonstrate that DAP5 associates with
      eIF2beta and eIF4AI to stimulate IRES-dependent translation of cellular mRNAs. In
      contrast, DAP5 is dispensable for cap-dependent translation. These findings
      provide the first mechanistic insights into the function of DAP5 as a selective
      regulator of cap-independent translation. 

PMID- 25779045
TI  - Chemical and structural characterization of interstrand cross-links formed
      between abasic sites and adenine residues in duplex DNA.
AB  - A new type of interstrand DNA-DNA cross-link between abasic (Ap) sites and 2'
      deoxyadenosine (dA) residues was recently reported, but the chemical structure
      and properties of this lesion were not rigorously established. Here we
      characterized the nucleoside cross-link remnant released by enzymatic digestion
      of duplex DNA containing the dA-Ap cross-link. A synthetic standard was prepared
      for the putative nucleoside cross-link remnant 6 in which the anomeric carbon of
      the 2-deoxyribose residue was connected to the exocyclic N(6)-amino group of dA.
      Liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis showed that
      the synthetic material 6: matched the authentic cross-link remnant released by
      enzymatic digestion of cross-linked DNA. These findings establish the chemical
      structure of the dA-Ap cross-link released from duplex DNA and may provide
      methods for the detection of this lesion in cellular DNA. Both the nucleoside
      cross-link remnant 6: and the cross-link in duplex DNA were quite stable at pH 7
      and 37 degrees C, suggesting that the dA-Ap cross-link could be a persistent
      lesion with the potential to block the action of various DNA processing enzymes. 

PMID- 25779046
TI  - An Lnc RNA (GAS5)/SnoRNA-derived piRNA induces activation of TRAIL gene by site
      specifically recruiting MLL/COMPASS-like complexes.
AB  - PIWI-interacting RNA (piRNA) silences the transposons in germlines or induces
      epigenetic modifications in the invertebrates. However, its function in the
      mammalian somatic cells remains unknown. Here we demonstrate that a piRNA derived
      from Growth Arrest Specific 5, a tumor-suppressive long non-coding RNA, potently
      upregulates the transcription of tumor necrosis factor (TNF)-related apoptosis
      inducing ligand (TRAIL), a proapoptotic protein, by inducing H3K4
      methylation/H3K27 demethylation. Interestingly, the PIWIL1/4 proteins, which bind
      with this piRNA, directly interact with WDR5, resulting in a site-specific
      recruitment of the hCOMPASS-like complexes containing at least MLL3 and UTX
      (KDM6A). We have indicated a novel pathway for piRNAs to specially activate gene
      expression. Given that MLL3 or UTX are frequently mutated in various tumors, the
      piRNA/MLL3/UTX complex mediates the induction of TRAIL, and consequently leads to
      the inhibition of tumor growth. 

PMID- 25779047
TI  - Embryonic expression of endogenous retroviral RNAs in somatic tissues adjacent to
      the Oikopleura germline.
AB  - Selective pressure to maintain small genome size implies control of transposable
      elements, and most old classes of retrotransposons are indeed absent from the
      very compact genome of the tunicate Oikopleura dioica. Nonetheless, two families
      of retrotransposons are present, including the Tor elements. The gene
      organization within Tor elements is similar to that of LTR retrotransposons and
      retroviruses. In addition to gag and pol, many Tor elements carry a third gene
      encoding viral envelope-like proteins (Env) that may mediate infection. We show
      that the Tor family contains distinct classes of elements. In some classes, env
      mRNA is transcribed from the 5'LTR as in retroviruses. In others, env is
      transcribed from an additional promoter located downstream of the 5'LTR. Tor Env
      proteins are membrane-associated glycoproteins which exhibit some features of
      viral membrane fusion proteins. Whereas some elements are expressed in the adult
      testis, many others are specifically expressed in embryonic somatic cells
      adjacent to primordial germ cells. Such embryonic expression depends on
      determinants present in the Tor elements and not on their surrounding genomic
      environment. Our study shows that unusual modes of transcription and expression
      close to the germline may contribute to the proliferation of Tor elements. 

PMID- 25779048
TI  - Epstein-Barr virus transcription factor Zta acts through distal regulatory
      elements to directly control cellular gene expression.
AB  - Lytic replication of the human gamma herpes virus Epstein-Barr virus (EBV) is an
      essential prerequisite for the spread of the virus. Differential regulation of a
      limited number of cellular genes has been reported in B-cells during the viral
      lytic replication cycle. We asked whether a viral bZIP transcription factor, Zta
      (BZLF1, ZEBRA, EB1), drives some of these changes. Using genome-wide chromatin
      immunoprecipitation coupled to next-generation DNA sequencing (ChIP-seq) we
      established a map of Zta interactions across the human genome. Using sensitive
      transcriptome analyses we identified 2263 cellular genes whose expression is
      significantly changed during the EBV lytic replication cycle. Zta binds 278 of
      the regulated genes and the distribution of binding sites shows that Zta binds
      mostly to sites that are distal to transcription start sites. This differs from
      the prevailing view that Zta activates viral genes by binding exclusively at
      promoter elements. We show that a synthetic Zta binding element confers Zta
      regulation at a distance and that distal Zta binding sites from cellular genes
      can confer Zta-mediated regulation on a heterologous promoter. This leads us to
      propose that Zta directly reprograms the expression of cellular genes through
      distal elements. 

PMID- 25779049
TI  - mRNA maturation in giant viruses: variation on a theme.
AB  - Giant viruses from the Mimiviridae family replicate entirely in their host
      cytoplasm where their genes are transcribed by a viral transcription apparatus.
      mRNA polyadenylation uniquely occurs at hairpin-forming palindromic sequences
      terminating viral transcripts. Here we show that a conserved gene cluster both
      encode the enzyme responsible for the hairpin cleavage and the viral polyA
      polymerases (vPAP). Unexpectedly, the vPAPs are homodimeric and uniquely self
      processive. The vPAP backbone structures exhibit a symmetrical architecture with
      two subdomains sharing a nucleotidyltransferase topology, suggesting that vPAPs
      originate from an ancestral duplication. A Poxvirus processivity factor homologue
      encoded by Megavirus chilensis displays a conserved 5'-GpppA 2'O
      methyltransferase activity but is also able to internally methylate the mRNAs'
      polyA tails. These findings elucidate how the arm wrestling between hosts and
      their viruses to access the translation machinery is taking place in Mimiviridae.

PMID- 25779050
TI  - Invadolysin acts genetically via the SAGA complex to modulate chromosome
      structure.
AB  - Identification of components essential to chromosome structure and behaviour
      remains a vibrant area of study. We have previously shown that invadolysin is
      essential in Drosophila, with roles in cell division and cell migration. Mitotic
      chromosomes are hypercondensed in length, but display an aberrant fuzzy
      appearance. We additionally demonstrated that in human cells, invadolysin is
      localized on the surface of lipid droplets, organelles that store not only
      triglycerides and sterols but also free histones H2A, H2Av and H2B. Is there a
      link between the storage of histones in lipid droplets and the aberrantly
      structured chromosomes of invadolysin mutants? We have identified a genetic
      interaction between invadolysin and nonstop, the de-ubiquitinating protease
      component of the SAGA (Spt-Ada-Gcn5-acetyltransferase) chromatin-remodelling
      complex. invadolysin and nonstop mutants exhibit phenotypic similarities in terms
      of chromosome structure in both diploid and polyploid cells. Furthermore, IX
      14(1)/not(1) transheterozygous animals accumulate mono-ubiquitinated histone H2B
      (ubH2B) and histone H3 tri-methylated at lysine 4 (H3K4me3). Whole mount
      immunostaining of IX-14(1)/not(1) transheterozygous salivary glands revealed that
      ubH2B accumulates surprisingly in the cytoplasm, rather than the nucleus. Over
      expression of the Bre1 ubiquitin ligase phenocopies the effects of mutating
      either the invadolysin or nonstop genes. Intriguingly, nonstop and mutants of
      other SAGA subunits (gcn5, ada2b and sgf11) all suppress an invadolysin-induced
      rough eye phenotype. We conclude that the abnormal chromosome phenotype of
      invadolysin mutants is likely the result of disrupting the histone modification
      cycle, as accumulation of ubH2B and H3K4me3 is observed. We further suggest that
      the mislocalization of ubH2B to the cytoplasm has additional consequences on
      downstream components essential for chromosome behaviour. We therefore propose
      that invadolysin plays a crucial role in chromosome organization via its
      interaction with the SAGA complex. 

PMID- 25779051
TI  - What matters for lac repressor search in vivo--sliding, hopping, intersegment
      transfer, crowding on DNA or recognition?
AB  - We have investigated which aspects of transcription factor DNA interactions are
      most important to account for the recent in vivo search time measurements for the
      dimeric lac repressor. We find the best agreement for a sliding model where non
      specific binding to DNA is improbable at first contact and the sliding LacI
      protein binds at high probability when reaching the specific Osym operator. We
      also find that the contribution of hopping to the overall search speed is
      negligible although physically unavoidable. The parameters that give the best fit
      reveal sliding distances, including hopping, close to what has been proposed in
      the past, i.e. ~40 bp, but with an unexpectedly high 1D diffusion constant on non
      specific DNA sequences. Including a mechanism of inter-segment transfer between
      distant DNA segments does not bring down the 1D diffusion to the expected
      fraction of the in vitro value. This suggests a mechanism where transcription
      factors can slide less hindered in vivo than what is given by a simple viscosity
      scaling argument or that a modification of the model is needed. For example, the
      estimated diffusion rate constant would be consistent with the expectation if
      parts of the chromosome, away from the operator site, were inaccessible for
      searching. 

PMID- 25779052
TI  - Distinguishing between productive and abortive promoters using a random forest
      classifier in Mycoplasma pneumoniae.
AB  - Distinguishing between promoter-like sequences in bacteria that belong to true or
      abortive promoters, or to those that do not initiate transcription at all, is one
      of the important challenges in transcriptomics. To address this problem, we have
      studied the genome-reduced bacterium Mycoplasma pneumoniae, for which the RNAs
      associated with transcriptional start sites have been recently experimentally
      identified. We determined the contribution to transcription events of different
      genomic features: the -10, extended -10 and -35 boxes, the UP element, the bases
      surrounding the -10 box and the nearest-neighbor free energy of the promoter
      region. Using a random forest classifier and the aforementioned features
      transformed into scores, we could distinguish between true, abortive promoters
      and non-promoters with good -10 box sequences. The methods used in this
      characterization of promoters can be extended to other bacteria and have
      important applications for promoter design in bacterial genome engineering. 

PMID- 25779053
TI  - The nuclease FAN1 is involved in DNA crosslink repair in Arabidopsis thaliana
      independently of the nuclease MUS81.
AB  - Fanconi anemia is a severe genetic disorder. Mutations in one of several genes
      lead to defects in DNA crosslink (CL) repair in human cells. An essential step in
      CL repair is the activation of the pathway by the monoubiquitination of the
      heterodimer FANCD2/FANCI, which recruits the nuclease FAN1 to the CL site.
      Surprisingly, FAN1 function is not conserved between different eukaryotes. No
      FAN1 homolog is present in Drosophila and Saccharomyces cerevisiae. The FAN1
      homolog in Schizosaccharomyces pombe is involved in CL repair; a homolog is
      present in Xenopus but is not involved in CL repair. Here we show that a FAN1
      homolog is present in plants and it is involved in CL repair in Arabidopsis
      thaliana. Both the virus-type replication-repair nuclease and the ubiquitin
      binding ubiquitin-binding zinc finger domains are essential for this function.
      FAN1 likely acts upstream of two sub-pathways of CL repair. These pathways are
      defined by the Bloom syndrome homolog RECQ4A and the ATPase RAD5A, which is
      involved in error-free post-replicative repair. Mutations in both FAN1 and the
      endonuclease MUS81 resulted in greater sensitivity against CLs than in the
      respective single mutants. These results indicate that the two nucleases define
      two independent pathways of CL repair in plants. 

PMID- 25779054
TI  - Does nurse-led initiation of Ottawa ankle rules reduce ED length of stay?
AB  - INTRODUCTION: Ankle injuries can account for up to 3.8% of UK Emergency
      Department (ED) presentations per annum and this figure is comparative to the
      4.4% in North America. Growing ED attendance impacts on crowding, waiting times,
      patient satisfaction and service provision. One way to streamline service would
      be widespread use of the Ottawa Ankle Rules (OAR), which reduces the need to wait
      for radiography. AIM: To examine the best available evidence on the impact of OAR
      on ED length of stay (LoS) following standard systematic review methodology.
      METHODS: A systematic search was undertaken in the CINAHL, EMBASE, MEDLINE,
      SCOPUS, and BNI databases. Studies that examined OAR use in the ED adult
      population were considered. Four studies met the inclusion criteria and were
      included in the narrative synthesis. RESULTS: All four studies point towards a
      reduction in LoS following OAR introduction. The quality of the body of evidence
      is considered to be low due to moderate risk of bias and indirectness between the
      studies. DISCUSSION: A strong body of evidence supports OAR use in reducing
      radiography but further research is needed to explore impact on LoS. This would
      inform clinical practice and potentially combat current pressures faced within
      EDs worldwide.

PMID- 25779056
TI  - [Possibility of the influence that environmental factors give to allergy in
      pediatrics domain].

PMID- 25779057
TI  - [Target molecules for the treatment of allergic diseases].

PMID- 25779055
TI  - Age-dependent association between sex and renal cell carcinoma mortality: a
      population-based analysis.
AB  - Research on sex differences in renal cancer-specific mortality (RCSM), which
      considered the sex effect to be constant throughout life, has yielded conflicting
      results. This study hypothesized the sex effect may be modified by age, which is
      a proxy for hormonal status. Data from the Surveillance, Epidemiology and End
      Results database (1988-2010) were used to identify 114,539 patients with renal
      cell carcinoma (RCC). The study cohort was divided into three age groups using
      cutoffs of 42 and 58 years, which represent the premenopausal and postmenopausal
      periods. The cumulative incidence function and competing risks analyses were used
      to examine the effect of covariates on RCSM and other-cause mortality (OCM). In
      premenopausal period, male sex was a significant predictor of poor RCSM for both
      localized (adjusted subdistribution hazard ratio [aSHR] = 1.63, P = 0.002) and
      advanced (aSHR = 1.20, P = 0.041) disease. In postmenopausal period, the sex
      disparity diminished (aSHR = 1.05, P = 0.16) and reversed (aSHR = 0.95, P =
      0.017) in localized and advanced disease, respectively. On the contrary, similar
      trend was not found for OCM across all age groups. Our results demonstrated the
      sex effect on RCSM was strongly modified by age. These findings may aid in
      clinical practice and need further evaluation of underlying biological
      mechanisms.

PMID- 25779058
TI  - [Current status and perspective of molecular-targeted therapy in asthma].

PMID- 25779059
TI  - [JSA anaphylaxis guideline -importance of basic management and prevention].

PMID- 25779060
TI  - [Clinical practice of collagen diseases from a dermatological standpoint].

PMID- 25779062
TI  - [Group 2 innate lymphoid cells (ILC2s)].

PMID- 25779061
TI  - [Eosinophilic chronic rhinosinusitis].

PMID- 25779063
TI  - [A case of eosinophilic esophagogastroenteritis which developed after rush oral
      immunotherapy for egg allergy].
AB  - Rush oral immunotherapy was provided to a 9 year old boy suffering from egg
      allergy. The patient reached the goal of one boiled egg daily on day 22 of
      treatment. He was discharged from the hospital the following day, with the
      maintenance dose of one whole egg to be taken daily. However, the patient began
      to experience abdominal pain and vomiting after ingestion of egg approximately
      one day after discharge. Blood tests revealed a remarkable increase in
      eosinophils in peripheral blood, and we reduced the patient's intake of egg. The
      patient's condition did not improve, and he gradually started to lose weight.
      Maintenance dosing was stopped completely on day 38. An endoscopic biopsy of the
      mucosa lining from the esophagus to the duodenum was performed on day 45. The
      results confirmed prominent diffuse eosinophilic infiltration of the entire upper
      gastrointestinal tract. The patient was finally diagnosed with eosinophil
      esophagogastroenteritis. While this condition is rare, it should be considered in
      future cases of persistent gastrointestinal symptoms during food allergy
      immunotherapy. 

PMID- 25779064
TI  - [A case of anaphylaxis caused by enokitake (Flammulina velutipes) ingestion].
AB  - Enokitake (Flammulina velutipes, winter mushroom) is a common edible mushroom in
      Japan. We experienced a case of anaphylaxis after enokitake ingestion. There are
      no reports describing anaphylaxis caused by the ingestion of this mushroom.
      Enokitake allergen has also not been reported. We thus attempted to identify
      enokitake allergen using the patient's serum. The patient was a seventeen-year
      old woman who had had no episodes of food allergy and experienced anaphylaxis
      after the ingestion of sukiyaki (beef, pork, tofu, vegetables, enokitake, etc.).
      She had previously eaten sukiyaki (the same ingredients) without any symptoms.
      The result of enokitake skin prick to prick test was positive. Oral food
      challenge was positive, inducing anaphylaxis. We performed western blotting with
      enokitake extract and the patient's serum. Three enokitake protein bands (18 kDa,
      39 kDa, 50 kDa) reacted specifically with the patient's IgE. 

PMID- 25779066
TI  - [Struggle forward in the golden time of stomatological medical development].

PMID- 25779067
TI  - [Overturning challenges of big data against conventional medicine].

PMID- 25779065
TI  - Increased maternal T cell microchimerism in the allogeneic fetus during LPS
      induced preterm labor in mice.
AB  - Fetal surgery is a promising strategy to treat fetuses with severe congenital
      abnormalities but its clinical applications are often limited by preterm labor.
      In normal pregnancy, multiple mechanisms protect the semi-allogeneic fetus from
      attack by maternal T cells. Maternal microchimerism (the presence of maternal
      cells in the fetus) has been suggested to be one mechanism of maternal-fetal
      tolerance in that it exposes the fetus to non-inherited maternal antigens and
      leads to the generation of fetal regulatory T cells that can suppress a maternal
      T cell response. Preterm labor may represent a breakdown of this robust tolerance
      network. We hypothesized that during inflammation-associated preterm labor,
      maternal leukocytes cross the maternal-fetal interface and enter the fetal
      circulation. Consistent with this hypothesis, we found that during preterm labor
      in mice, the percentage of maternal microchimerism in fetal blood increased and
      the frequency of fetuses with high levels of trafficking (greater than 0.5%) also
      increased. Finally, we showed that the maternal leukocytes trafficking into the
      fetus are primarily Gr-1(+) cells in both syngeneic and allogeneic pregnancy,
      while T cell trafficking into the fetus specifically increases during allogeneic
      pregnancies. Our results demonstrate that trafficking of maternal leukocytes
      during pregnancy is altered during preterm labor. Such alterations may be
      clinically significant in affecting maternal-fetal tolerance. 

PMID- 25779068
TI  - [An application of cone-beam CT in the diagnosis of bone defects for chronic
      periodontitis].
AB  - OBJECTIVE: To evaluate the accuracy of cone-beam CT (CBCT) for detection of bone
      defects in chronic periodontitis and its consistency with periapical film,
      panoramic radiograph and clinical examination. METHODS: Seventy-five patients
      with periodontitis were selected in the study. Each patient received clinical
      examination, periapical film, panoramic radiograph and CBCT examination one week
      after supragingival scaling. The distance from the alveolar ridge crest to
      enamelo-cemental junction was measured. The data were statistically analyzed.
      RESULTS: A total of 1 494 teeth and 8 964 sites were included in the study. Among
      the three kinds of imaging methods only CBCT could detect the lip (buccal) or
      tongue (palatine) side of alveolar bone destruction. Compared with panoramic
      radiographs[mesial: (4.9+/-0.4) mm, distal: (4.9+/-0.8) mm] and periapical film
      [mesial: (5.1+/-0.6) mm, distal: (5.1+/-0.8) mm], CBCT [mesial: (5.5+/-0.4) mm,
      distal: (5.6+/-0.8) mm] showed significant differences (P < 0.01) in alveolar
      bone defect measurements in detecting mesial and distal alveolar bone defect.
      There was no significant difference between clinical probing [mesial: (5.5+/-0.6)
      mm, distal: (5.5+/-0.6) mm] and CBCT. CONCLUSIONS: CBCT have the highest
      consistency with clinical probing in detecting the alveolar bone loss in chronic
      periodontitis.

PMID- 25779069
TI  - [The expression and clinical significance of BATF2 in oral tongue squamous cell
      carcinoma].
AB  - OBJECTIVES: To investigate the expression and clinical significance of BATF2 in
      the oral tongue squamous cell carcinoma (OTSCC). METHODS: Expression of BATF2
      mRNA and protein in 16 paired OTSCC tissues and adjacent non-tumor mucosa were
      examined using quantitative PCR, western blotting analysis and
      immunohistochemistry assays, and the relation between BATF2 expression and
      clinical pathologic factor and prognosis was analyzed. RESULTS: In 16 paired
      tissues, expression of BATF2 mRNA in 13 OTSCC tissues and expression of BATF2
      protein in 14 OTSCC tissues were significantly lower than that in adjacent non
      tumor mucosa. In 202 paraffin-embedded OTSCC samples, BATF2 was not expressed in
      20 cases (9.9%), low expressed in 104 cases (51.5%) and highly expressed in 78
      (38.6%). BATF2 expression level was significantly correlated with histological
      differentiation (P = 0.002). Patients with low BATF2 expression had significantly
      poorer overall survival and disease-free survival than those with high BATF2
      expression (P < 0.001). CONCLUSIONS: BATF2 was low expressed in OTSCC and related
      to tumor differentiation and prognosis and may serve as a prognostic biomarker
      and potential therapeutic target for this disease.

PMID- 25779070
TI  - [Raman spectral characteristics of oral squamous cell carcinoma, epithelial
      dysplasia and normal mucosa].
AB  - OBJECTIVE: To investigate the Raman spectral characteristics of oral squamous
      cell carcinoma, high-grade epithelial dysplasia and normal mucosa. METHODS: Fifty
      six fresh samples of oral carcinoma, 50 of high-grade epithelial dysplasia and
      32 of normal mucosa were collected. The i-Raman spectrometer with an optical
      fiber tube was applied to acquire Raman spectrum. The diagnostic model
      established by principle component analysis (PCA) and discriminant function
      analysis (DFA) was used to analyze and classify the spectra of different samples.
      RESULTS: There were significant differences among the Raman spectra of these
      samples. Compared with the spectra of normal mucosa, the spectra of oral
      carcinoma and dysplasia showed strong peaks which were contributed to nucleic
      acids, proteins and lipids. The diagnostic models established by PCA-DFA could
      successfully classify these Raman spectra of different samples with a high
      accuracy of 96.4% (133/138). The model was evaluated by 'Leave one out' cross
      validation and reached a high accuracy of 92.8% (128/138). CONCLUSIONS: The
      proliferation and metabolism of oral squamous cell carcinoma and epithelial high
      grade dysplasia are more active than normal mucosa. The diagnostic models
      established by PCA-DFA can classify these Raman spectra of different samples with
      a high accuracy.

PMID- 25779071
TI  - [Expression of miRNA-155 and miRNA-146a in peripheral blood mononuclear cells and
      plasma of oral lichen planus patients].
AB  - OBJECTIVE: To investigate the expression and clinical significance of miRNA-155
      and miRNA-146a in peripheral blood mononuclear cells (PBMC) and plasma of oral
      lichen planus (OLP) patients. METHODS: Twenty-five female and seven male OLP
      patients (OLP group) aged 25 to 54 years were selected from January 2012 to May
      2013. The diagnosis was confirmed by pathology and the lesions were divided into
      two non-erosive OLP group (18 cases) and erosive OLP group (14 cases). Twenty
      healthy sex and age matched volunteers served as control. miRNA-155 and miRNA
      146a expressions in PBMC and plasma were examined by real-time PCR. The
      difference between OLP group and control group was statistically analyzed.
      RESULTS: The expressions of PBMC and plasma miRNA-155 were higher in OLP patients
      than those in the healthy control (median, 0.07 vs 0.03, P < 0.05; 5.84 vs 1.32,
      P < 0.01). The median expression level of miRNA-146a in PBMC and plasma of OLP
      patients and healthy controls were (1.26 vs 0.58, P < 0.05) and (412.60 vs
      238.42, P < 0.01). The plasma miRNA-155 and miRNA-146a expressions were
      significantly higher in erosive OLP group than those in non-erosive OLP group.
      There were no significant differences in the expression of PBMC miRNA-155 and
      miRNA-146a between the two groups. CONCLUSIONS: The expressions of PBMC and
      plasma miRNA-155 and miRNA-146a are higher in OLP patients. The expressions of
      plasma miRNA-155 and miRNA-146a are associated with OLP severity. The over
      expression of miRNA-155 and miRNA-146a in OLP may play a role in the pathogenesis
      of OLP.

PMID- 25779072
TI  - [Fluoride release and recharge properties of six restorative materials].
AB  - OBJECTIVE: To evaluate the F(-) releasing and recharging properties of six dental
      restorative materials. METHODS: Disc specimens 10 mm in diameter and 1 mm in
      thickness were prepared from 6 different dental restorative materials: Fuji VII
      [glass ionomer cement (GIC)], Fuji II LC (light-curing, GIC), Beautifil (giomer),
      Compoglass F (compomer), Charisma (composite) and Experimental I (a fluoride
      releasing composite), with 10 discs for each material. Specimens were dipped in 5
      ml deionized water and F(-) release was detected using a fluoride-specific ion
      electrode every day from 1-7 days and every three days from 8-28 days. On day 28,
      specimens were exposed to a fluoride foam for 4 min and then dipped in water,
      then the F(-) concentration was detected every day for a week. The specimens were
      exposed to fluoride foam and fluoride release was detected repeatedly for three
      times. RESULTS: All materials presented the highest F(-) release on the first day
      after dipping and the F(-) release sharply decreased after 24 h and slowly
      decreased after 3 days. On the first day, Fuji VII presented the highest F(-)
      release[(99.68+/-15.21) ug*cm(-2)*d(-1)], followed by Fuji II LC [(37.12+/-1.67)
      ug*cm(-2)*d(-1)], Experimental I [(22.93+/-1.53) ug*cm(-2)*d(-1)], Compoglass
      F[(15.28+/-0.70) ug*cm(-2)*d(-1)], Beautifil[(2.40+/-0.52) ug*cm(-2)*d(-1)] and
      Charisma[(0.11+/-0.02) ug*cm(-2)*d(-1)]. Within 28 days of dipping, both Fuji VII
      and Fuji II LC released more F(-) than other materials did(P < 0.05), followed by
      Compoglass F and Experimental I, and Beautifil and Charisma released the least F(
      )(P < 0.01). After F(-) uptake, all materials released the highest F- on the
      first day and presented sharply decrease after 24 h and slowly decrease after 2
      days. On the first day after F(-) uptake, Fuji VII presented the highest F(-)
      release (>40 ug*cm(-2) *d(-1)), much more than other materials(P < 0.01),
      followed by Fuji II LC(>25 ug*cm(-2) *d(-1)). Beautifil, Compoglass F and
      Experimental I were close in F(-) release value(15- 20 ug * cm(-2) * d(-1)), and
      Charisma showed the lowest F(-) release. CONCLUSIONS: Two glass ionomers were
      shown to have highest capacity in F(-) release and uptake, followed by compomer
      and fluoride releasing composite. Composite demonstrated the lowest F(-) release
      and uptake and Giomer was comparable to composite in F(-) release and to compomer
      and fluoride releasing composite in F(-) uptake.

PMID- 25779073
TI  - [Comparative study on contact guidance activity of human gingival fibroblasts on
      microgroove surfaces].
AB  - OBJECTIVE: To compared the difference in contact guidance activity among
      microgroove surfaces with different sizes of human gingival fibroblast (HGF),
      with the hope of providing basis for size selection of microgroove for
      transmucosal part of dental implant. METHODS: Basing on the size of HGF,
      microgroove titanium surfaces were fabricated by photolithography with parallel
      grooves: 15, 30 or 60 um in width and 5 or 10 um in depth. The groups that used
      different microgroove surfaces were denoted as T15/5, T15/10, T30/5, T30/10,
      T60/5, and T60/10. Group T0 (the control meanwhile was a sputter of titanium on a
      simple planar silicon substrate). The morphology that HGF arranged along the
      groove was analyzed by immunofluorescence staining. Difference in contact
      guidance activity was quantitatively compared basing on the consistency of
      nucleus arrangement and deformation ratio. RESULTS: Microgroove groups had
      significantly higher consistency of nucleus arrangement and deformation ratio
      compared to the control group, with T60/10 had the highest consistency of 0.937+/
      0.024, and T15/5 had the lowest consistency of 0.660+/-0.016 and T60/10 had the
      highest deformation ratio of 3.555+/-0.205, and T15/5 had the lowest deformation
      ratio of 1.819+/-0.011. CONCLUSIONS: Microgroove surfaces of all the different
      sizes show contact guidance activity on HGF, and the contact guidance activity
      increases with the increase of width and depth.

PMID- 25779074
TI  - [Effect of fluo-hydroxyapatite on biological properies of osteosarcoma MG63
      cells].
AB  - OBJECTIVE: To investigate the effects of 20% fluor-hydroxyapatite (FHA) on
      proliferation and osteogenic differentiation of human MG63 osteosarcoma cells.
      METHODS: FHA was prepared by chemical precipitation method, and its structure and
      surface features were tested by scanning microscope, X-ray diffraction (XRD) and
      Fourier transform infrared spectroscopy. MG63 cells were cultured and divided
      into FHA, hydroxyapatite (HA) and control groups (n = 3). The proliferation of
      the cells was evaluated using methylthiazol tetrazolium (MTT) assay. ALP activity
      of the cells was assessed. Osteogenic differentiation was evaluated based on the
      reverse transcription PCR (RT-PCR) of differentiation-related genes, namely,
      collagen type I (Col I), alkaline phosphatase (ALP), osteocalcin (OCN) and core
      binding factor alpha1 (Cbfalpha1). The data were analyzed statistically by one
      way analysis of variance using SPSS 13.0 software. RESULTS: XRD test showed that
      the main crystalline phase of FHA was similar to that of HA. Absorptance value of
      cells exposed to FHA(1.87+/-0.06) measured by MTT was higher than that of the
      control(1.25+/-0.02) on the third day(P < 0.05), and there was no statistically
      significant difference between the cells exposed to FHA and HA(1.84+/-0.03) (P >
      0.05). ALP activity of the cells exposed to FHA(4.62+/-0.09)was higher than that
      of the control (1.92 +/- 0.05) (P < 0.05). RT-PCR tests showed that compared with
      the control, FHA up-regulated the expression of Col I, ALP and OCN mRNA, down
      regulated the expression of Cbfalpha1 mRNA. CONCLUSIONS: FHA enhances the
      proliferation and osteogenic differentiation-related gene expression, and has
      good biocompatibility.

PMID- 25779075
TI  - [The research on optical properties of four all-ceramic veneer materials].
AB  - OBJECTIVE: To analyze the color parameters and translucency of four frequently
      used veneer materials. METHODS: Forty disc specimens[(1.00+/-0.01) mm in
      thickness, 10 mm in diameter] were fabricated according to the manufacturer's
      instructions with IPS Empress((r)) CAD[A2, high translucency (HT)], IPS
      e.max((r)) Press(A2, HT), IPS e.max((r)) CAD (A2, HT) and VITABLOCS((r)) Mark II
      (A2) respectively and were divided into Groups A, B, C, D. All of the specimens
      were ground and polished on a grinding machine. Then color parameters (L*, a*,
      b*) and transmittance (tau) were measured using spectrocolorimeter and
      transmissivity testing device. The color parameters of the specimens were
      compared to the color parameters of A2 shade of Ivoclar Vivadent A-D shade guide.
      The data were analyzed with one-way analysis of variance (ANOVA), and mean values
      were compared by the Tukey's test (alpha = 0.05). RESULTS: There was no
      statistical difference between the color parameters L*, a*, b* and C*ab of Group
      A and Group D (P > 0.05). But the color parameters of those two ceramic materials
      were statistically different from the color parameters of Group B and Group C (P
      < 0.05). There was no statistical difference between color parameters b* and C*ab
      of Group B and Group C(P > 0.05). However, the color parameters L* and a* of the
      two materials were statistically different(P < 0.05). The color differences
      (DeltaE) between Group A, B, C, D and standard A2 were 6.05+/-0.12, 5.11+/-0.27,
      3.73+/-0.27, 6.30+/-0.38 respectively. The transmittances of Group A, B, C, D
      were (29.69+/-0.31)%, (25.83+/-0.36) %, (28.92+/-0.47)% and (26.94+/-0.33)%
      respectively. CONCLUSIONS: The color parameters of these four materials are
      different. Their transmittance are relatively high but statistically different.
      The color difference (DeltaE) between IPS e.max((r)) CAD (A2, HT) and standard A2
      is lowest among all the groups.

PMID- 25779076
TI  - [Clinical application of fully guided surgery in dental implant].

PMID- 25779077
TI  - [Clinical diagnosis of oral hereditary diseases].

PMID- 25779078
TI  - [Research progress in immediate implant and provisionalization in the esthetic
      zone].

PMID- 25779079
TI  - [The clinical research progress in the neck cystic metastatic squamous cell
      carcinoma].

PMID- 25779080
TI  - [Case report: nevoid basal cell carcinoma syndrome in a child with hypertension].

PMID- 25779081
TI  - On the mechanism underlying ethanol-induced mitochondrial dynamic disruption and
      autophagy response.
AB  - We have explored the mechanisms underlying ethanol-induced mitochondrial dynamics
      disruption and mitophagy. Ethanol increases mitochondrial fission in a
      concentration-dependent manner through Drp1 mitochondrial translocation and OPA1
      proteolytic cleavage. ARPE-19 (a human retinal pigment epithelial cell line)
      cells challenged with ethanol showed mitochondrial potential disruptions mediated
      by alterations in mitochondrial complex IV protein level and increases in
      mitochondrial reactive oxygen species production. In addition, ethanol activated
      the canonical autophagic pathway, as denoted by autophagosome formation and
      autophagy regulator elements including Beclin1, ATG5-ATG12 and P-S6 kinase.
      Likewise, autophagy inhibition dramatically increased mitochondrial fission and
      cell death, whereas autophagy stimulation rendered the opposite results, placing
      autophagy as a cytoprotective response aimed to remove damaged mitochondria.
      Interestingly, although ethanol induced mitochondrial Bax translocation, this
      episode was associated to cell death rather than mitochondrial fission or
      autophagy responses. Thus, Bax required 600 mM ethanol to migrate to
      mitochondria, a concentration that resulted in cell death. Furthermore, mouse
      embryonic fibroblasts lacking this protein respond to ethanol by undergoing
      mitochondrial fission and autophagy but not cytotoxicity. Finally, by using the
      specific mitochondrial-targeted scavenger MitoQ, we revealed mitochondria as the
      main source of reactive oxygen species that trigger autophagy activation. These
      findings suggest that cells respond to ethanol activating mitochondrial fission
      machinery by Drp1 and OPA1 rather than bax, in a manner that stimulates
      cytoprotective autophagy through mitochondrial ROS.

PMID- 25779082
TI  - Role of Akt and Ca2+ on cell permeabilization via connexin43 hemichannels induced
      by metabolic inhibition.
AB  - Connexin hemichannels are regulated under physiological and pathological
      conditions. Metabolic inhibition, a model of ischemia, promotes surface
      hemichannel activation associated, in part, with increased surface hemichannel
      levels, but little is known about its underlying mechanism. Here, we investigated
      the role of Akt on the connexin43 hemichannel's response induced by metabolic
      inhibition. In HeLa cells stably transfected with rat connexin43 fused to EGFP
      (HeLa43 cells), metabolic inhibition induced a transient Akt activation necessary
      to increase the amount of surface connexin43. The increase in levels of surface
      connexin43 was also found to depend on an intracellular Ca2+ signal increase that
      was partially mediated by Akt activation. However, the metabolic inhibition
      induced Akt activation was not significantly affected by intracellular Ca2+
      chelation. The Akt-dependent increase in connexin43 hemichannel activity in
      HeLa43 cells also occurred after oxygen-glucose deprivation, another ischemia
      like condition, and in cultured cortical astrocytes (endogenous connexin43
      expression system) under metabolic inhibition. Since opening of hemichannels has
      been shown to accelerate cell death, inhibition of Akt-dependent phosphorylation
      of connexin43 hemichannels could reduce cell death induced by
      ischemia/reperfusion.

PMID- 25779083
TI  - Metformin and caloric restriction induce an AMPK-dependent restoration of
      mitochondrial dysfunction in fibroblasts from Fibromyalgia patients.
AB  - Impaired AMPK is associated with a wide spectrum of clinical and pathological
      conditions, ranging from obesity, altered responses to exercise or metabolic
      syndrome, to inflammation, disturbed mitochondrial biogenesis and defective
      response to energy stress. Fibromyalgia (FM) is a world-wide diffused
      musculoskeletal chronic pain condition that affects up to 5% of the general
      population and comprises all the above mentioned pathophysiological states. Here,
      we tested the involvement of AMPK activation in fibroblasts derived from FM
      patients. AMPK was not phosphorylated in fibroblasts from FM patients and was
      associated with decreased mitochondrial biogenesis, reduced oxygen consumption,
      decreased antioxidant enzymes expression levels and mitochondrial dysfunction.
      However, mtDNA sequencing analysis did not show any important alterations which
      could justify the mitochondrial defects. AMPK activation in FM fibroblast was
      impaired in response to moderate oxidative stress. In contrast, AMPK activation
      by metformin or incubation with serum from caloric restricted mice improved the
      response to moderate oxidative stress and mitochondrial metabolism in FM
      fibroblasts. These results suggest that AMPK plays an essential role in FM
      pathophysiology and could represent the basis for a valuable new therapeutic
      target/strategy. Furthermore, both metformin and caloric restriction could be an
      interesting therapeutic approach in FM. 

PMID- 25779084
TI  - Identification of didecyldimethylammonium salts and salicylic acid as
      antimicrobial compounds in commercial fermented radish kimchi.
AB  - Daikon radish (Raphanus sativus) fermented with lactic acid bacteria, especially
      Leuconostoc or Lactobacillus spp., can be used to make kimchi, a traditional
      Korean fermented vegetable. Commercial Leuconostoc/radish root ferment filtrates
      are claimed to have broad spectrum antimicrobial activity. Leuconostoc kimchii
      fermentation products are patented as preservatives for cosmetics, and certain
      strains of this organism are reported to produce antimicrobial peptides
      (bacteriocins). We examined the antimicrobial agents in commercial
      Leuconostoc/radish root ferment filtrates. Both activity-guided fractionation
      with Amberlite XAD-16 and direct extraction with ethyl acetate gave salicylic
      acid as the primary agent with activity against Gram-negative bacteria. Further
      analysis of the ethyl acetate extract revealed that a didecyldimethylammonium
      salt was responsible for the Gram-positive activity. The structures of these
      compounds were confirmed by a combination of (1)H- and (13)C NMR, high
      performance liquid chromatography, high-resolution mass spectrometry, and tandem
      mass spectrometry analyses. Radiocarbon dating indicates that neither compound is
      a fermentation product. No antimicrobial peptides were detected. 

PMID- 25779085
TI  - The Prevalence of Child Sexual Abuse in Out-of-home Care: Increased Risk for
      Children with a Mild Intellectual Disability.
AB  - BACKGROUND: Children without disabilities in out-of-home care have a higher risk
      of child sexual abuse [CSA (Euser et al. 2013)]. In this study, we examined the
      year prevalence of CSA in out-of-home care for children with a mild intellectual
      disability, and compared it with the prevalence in out-of-home care for non
      disabled children and children in the general population. MATERIALS AND METHODS:
      Professionals (N = 104) from out-of-home care facilities reported cases of CSA
      that occurred in 2010 for the children they worked with (N = 1650). RESULTS: In
      out-of-home care for children with a mild intellectual disability, 9.8 per 1000
      children were victims of CSA. This prevalence was significantly higher than in
      regular out-of-home care and in the general population. CONCLUSION: Children with
      a mild intellectual disability in out-of-home care have an increased risk of CSA.
      Adequate education and support for both children and caregivers is necessary to
      recognize and prevent further sexual abuse.

PMID- 25779086
TI  - Aluminum oxide nanoparticles alter cell cycle progression through CCND1 and EGR1
      gene expression in human mesenchymal stem cells.
AB  - Aluminum oxide nanoparticles (Al2 O3 -NPs) are important ceramic materials that
      have been used in a variety of commercial and industrial applications. However,
      the impact of acute and chronic exposure to Al2 O3 -NPs on the environment and on
      human health has not been well studied. In this investigation, we evaluated the
      cytotoxic effects of Al2 O3 -NPs on human mesenchymal stem cells (hMSCs) by using
      a cell viability assay and observing cellular morphological changes, analyzing
      cell cycle progression, and monitoring the expression of cell cycle response
      genes (PCNA, EGR1, E2F1, CCND1, CCNC, CCNG1, and CYCD3). The Al2 O3 -NPs reduced
      hMSC viability in a dose- and time-dependent manner. Nuclear condensation and
      fragmentation, chromosomal DNA fragmentation, and cytoplasmic vacuolization were
      observed in Al2 O3 -NP-exposed cells. The nuclear morphological changes indicated
      that Al2 O3 -NPs alter cell cycle progression and gene expression. The cell cycle
      distribution revealed that Al2 O3 -NPs cause cell cycle arrest in the sub-G0-G1
      phase, and this is associated with a reduction in the cell population in the G2/M
      and G0/G1 phases. Moreover, Al2 O3 -NPs induced the upregulation of cell cycle
      response genes, including EGR1, E2F1, and CCND1. Our results suggested that
      exposure to Al2 O3 -NPs could cause acute cytotoxic effects in hMSCs through cell
      cycle regulatory genes. 

PMID- 25779087
TI  - The relation of baseline skills to psychotherapy outcome across diverse
      psychotherapies.
AB  - OBJECTIVE: We explored whether patients with varied levels of baseline deficits
      in compensatory skills and self-understanding had different outcomes across
      cognitive and dynamic therapies. METHOD: The assessment battery was administered
      at intake and termination (N = 97; 66% female, 81% Caucasian). We conducted
      regression analyses predicting symptom change from baseline levels of self
      understanding and compensatory skills. We also evaluated the interaction between
      baseline skill levels and treatment condition in the prediction of psychotherapy
      outcome. RESULTS: There was a significant interaction between treatment group and
      baseline compensatory skills in the prediction of Hamilton Depression Rating
      Scale (HAMD) symptom change, F(1,76) = 4.59, p = .035. Baseline deficits in
      compensatory skills were significantly related to symptom change for patients who
      received cognitive treatment, etarho = .40, p = .037, while baseline levels of
      self-understanding were not significantly predictive of treatment outcome in
      either condition. Baseline skill variables did not predict symptom change as
      measured by the HAMA. CONCLUSIONS: The findings support a capitalization model of
      cognitive therapy, whereby patients with relative strengths in compensatory
      skills at baseline have better treatment outcomes.

PMID- 25779088
TI  - Analysis of biosurfaces by neutron reflectometry: from simple to complex
      interfaces.
AB  - Because of its high sensitivity for light elements and the scattering contrast
      manipulation via isotopic substitutions, neutron reflectometry (NR) is an
      excellent tool for studying the structure of soft-condensed material. These
      materials include model biophysical systems as well as in situ living tissue at
      the solid-liquid interface. The penetrability of neutrons makes NR suitable for
      probing thin films with thicknesses of 5-5000 A at various buried, for example,
      solid-liquid, interfaces [J. Daillant and A. Gibaud, Lect. Notes Phys. 770, 133
      (2009); G. Fragneto-Cusani, J. Phys.: Condens. Matter 13, 4973 (2001); J.
      Penfold, Curr. Opin. Colloid Interface Sci. 7, 139 (2002)]. Over the past two
      decades, NR has evolved to become a key tool in the characterization of
      biological and biomimetic thin films. In the current report, the authors would
      like to highlight some of our recent accomplishments in utilizing NR to study
      highly complex systems, including in-situ experiments. Such studies will result
      in a much better understanding of complex biological problems, have significant
      medical impact by suggesting innovative treatment, and advance the development of
      highly functionalized biomimetic materials. 

PMID- 25779089
TI  - Emerging applications of low temperature gas plasmas in the food industry.
AB  - The global burden of foodborne disease due to the presence of contaminating micro
      organisms remains high, despite some notable examples of their successful
      reduction in some instances. Globally, the number of species of micro-organisms
      responsible for foodborne diseases has increased over the past decades and as a
      result of the continued centralization of the food processing industry, outbreaks
      now have far reaching consequences. Gas plasmas offer a broad range of
      microbicidal capabilities that could be exploited in the food industry and
      against which microbial resistance would be unlikely to occur. In addition to
      reducing the incidence of disease by acting on the micro-organisms responsible
      for food spoilage, gas plasmas could also play a role in increasing the shelf
      life of perishable foods and thereby reduce food wastage with positive financial
      and environmental implications. Treatment need not be confined to the food itself
      but could include food processing equipment and also the environment in which
      commercial food processing occurs. Moreover, gas plasmas could also be used to
      bring about the degradation of undesirable chemical compounds, such as allergens,
      toxins, and pesticide residues, often encountered on foods and food-processing
      equipment. The literature on the application of gas plasmas to food treatment is
      beginning to reveal an appreciation that attention needs also to be paid to
      ensuring that the key quality attributes of foods are not significantly impaired
      as a result of treatment. A greater understanding of both the mechanisms by which
      micro-organisms and chemical compounds are inactivated, and of the plasma species
      responsible for this is forming. This is significant, as this knowledge can then
      be used to design plasma systems with tailored compositions that will achieve
      maximum efficacy. Better understanding of the underlying interactions will also
      enable the design and implementation of control strategies capable of minimizing
      variations in plasma treatment efficacy despite perturbations in environmental
      and operational conditions. 

PMID- 25779091
TI  - Surgical team in India calls for mandatory enforcement of WHO safety checklist.

PMID- 25779092
TI  - The performance and stability of the oxygen reduction reaction on Pt-M (M = Pd,
      Ag and Au) nanorods: an experimental and computational study.
AB  - The ORR activity of Pt3M NRs is related to the oxophilicity (DeltaE(ads)).
      However, their segregation energy when exposed to oxygen containing species
      (OCS*) determines their stability. Although the DeltaE(ads) of Ag is not as weak
      as that of Au, its structure is relatively stable, thus promoting the ORR
      stability.

PMID- 25779090
TI  - Role of Ran-regulated nuclear-cytoplasmic trafficking of pVHL in the regulation
      of microtubular stability-mediated HIF-1alpha in hypoxic cardiomyocytes.
AB  - Our previous study suggested that microtubule network alteration affects the
      process of glycolysis in cardiomyocytes (CMs) via the regulation of hypoxia
      inducible factor (HIF)-1alpha during the early stages of hypoxia. However, little
      is known regarding the underlying mechanisms of microtubule network alteration
      induced changes of HIF-1alpha. The von Hippel-Lindau tumor suppressor protein
      (pVHL) has been shown to mediate the ubiquitination of HIF-1alpha in the nuclear
      compartment prior to HIF-1alpha exportation to the cytoplasm, and pVHL dynamic
      nuclear-cytoplasmic trafficking is indicated to be involved in the process of HIF
      1alpha degradation. In this study, by administering different microtubule
      stabilizing and -depolymerizing interventions, we demonstrated that microtubule
      stabilization promoted pVHL nuclear export and drove the translocation of pVHL to
      the cytoplasm, while microtubule disruption prevented pVHL nuclear export in
      hypoxic CMs. Moreover, the ratio between nuclear and cytoplasmic pVHL was
      associated with HIF-1alpha regulation. Importantly, microtubule network
      alteration also affected the subcellular localization of Ran, which was involved
      in the regulation of pVHL nuclear-cytoplasmic trafficking. The above results
      suggest that the subcellular translocation of pVHL plays an important role in
      microtubular structure alteration-induced HIF-1alpha regulation. Interestingly,
      Ran is involved in the process of pVHL nuclear-cytoplasmic trafficking following
      microtubule network alteration in hypoxic CMs. 

PMID- 25779093
TI  - The Development of the Ability to Semantically Integrate Information in Speech
      and Iconic Gesture in Comprehension.
AB  - We examined whether children's ability to integrate speech and gesture follows
      the pattern of a broader developmental shift between 3- and 5-year-old children
      (Ramscar & Gitcho, 2007) regarding the ability to process two pieces of
      information simultaneously. In Experiment 1, 3-year-olds, 5-year-olds, and adults
      were presented with either an iconic gesture or a spoken sentence or a
      combination of the two on a computer screen, and they were instructed to select a
      photograph that best matched the message. The 3-year-olds did not integrate
      information in speech and gesture, but 5-year-olds and adults did. In Experiment
      2, 3-year-old children were presented with the same speech and gesture as in
      Experiment 1 that were produced live by an experimenter. When presented live, 3
      year-olds could integrate speech and gesture. We concluded that development of
      the integration ability is a part of the broader developmental shift; however,
      live-presentation facilitates the nascent integration ability in 3-year-olds. 

PMID- 25779094
TI  - Comprehensive lymph node morphometry in rectal cancer using acetone compression.
AB  - AIMS: Acetone compression (AC) is an elution compression technique for the
      comprehensive pathological examination of fatty tissue. Here AC is combined with
      digital morphometry to evaluate the impact of preoperative (neoadjuvant)
      chemoradiotherapy (neoCRT) on lymph node (LN) numbers and morphology in locally
      advanced rectal cancer. AC is compared with complete embedding of the mesorectal
      fat (whole mesorectal embedding (WME)) to exclude artificial alterations and to
      the standard technique, manual dissectioning (MD). METHODS: 320 rectal cancer
      specimens were subjected to LN morphometry. Neoadjuvant CRT was applied in 204
      specimens. LNs were prepared either with AC (n=138), WME (n=51) or MD (n=131).
      8523 LNs were assessed including 530 nodes with metastases. RESULTS: LN prepared
      by AC and WME showed similar morphologies. AC revealed reduced LN sizes in neoCRT
      specimens compared with primary resection (2.2; 2.4 mm, p=0.049) while the LN
      number was comparable (27; 30/specimen). AC yielded 28 LN/specimen on average, MD
      yielded 22 LN (p<0.001). In neoCRT specimens, MD yielded less LN compared with
      primary resection (19; 25). MD detected less small LN (<2 mm; MD: 25%; AC: 56%)
      while 24 of the 135 LN metastases found by AC were <=2 mm in diameter.
      CONCLUSIONS: AC does not alter LN morphology and is especially suited to retrieve
      small LN after neoadjuvant CRT of rectal cancer. Neoadjuvant multimodality
      treatment caused reduced LN sizes while the LN numbers were not affected. When
      compared with MD, AC proved more reliable in the retrieval of LN from rectal
      cancer specimens after neoCRT.

PMID- 25779096
TI  - Synergetic compositional and morphological effects for improved Na+ storage
      properties of Ni3Co6S8-reduced graphene oxide composite powders.
AB  - The electrochemical properties of binary transition metal sulfide-reduced
      graphene oxide (RGO) composite powders, relevant for their performance as anode
      materials in sodium ion batteries, were firstly studied. (Ni,Co)O-RGO composite
      powders prepared by spray pyrolysis are transformed into Ni3Co6S8-RGO composite
      powders by a simple sulfidation process. Plate-shape nanocrystals of nickel
      cobalt sulfide (Ni3Co6S8) are uniformly distributed over the crumpled RGO
      structure. The discharge capacities of the Ni3Co6S8-RGO composite powders for
      2(nd) and 100(th) cycles at a current density of 0.5 A g(-1) are 504 and 498 mA h
      g(-1), respectively. However, the discharge capacities of the bare Ni3Co6S8
      powders for 2(nd) and 100(th) cycles are 522 and 125 mA h g(-1), respectively.
      The NiO-Co3O4 and (Ni,Co)O-RGO composite powders prepared by spray pyrolysis also
      show low discharge capacities of 122 and 119 mA h g(-1), respectively, after 100
      cycles. The high structural stability of the Ni3Co6S8-RGO composite powders
      during repeated sodium ion intercalation/deintercalation processes results in
      excellent cycling and rate performances for Na(+) storage. 

PMID- 25779095
TI  - Weakening of Corticomuscular Signal Coupling During Voluntary Motor Action in
      Aging.
AB  - BACKGROUND: Aging is associated with muscle weakness and impairment in performing
      skilled motor tasks. Still, little is known about whether the link or functional
      coupling or connection between the central and peripheral systems during
      voluntary motor performance is compromised in the elderly subjects. The purposes
      of this study were to estimate functional corticomuscular connection (CMC)
      strength in the elderly subjects by calculating EEG-EMG coherence during
      voluntary motor performance, determine the relationship between the CMC and
      voluntary muscle force, and compare these between the old and the young subjects.
      METHODS: Maximal voluntary contraction (MVC) of elbow flexion (EF) and EFs at
      three submaximal (20%, 50%, and 80% MVC) levels were performed in 28 healthy
      older (74.96+/-1.32 years) and 20 young (22.60+/-0.90 years) individuals, while
      EEG and EMG from biceps brachii, brachioradialis, and triceps brachii muscles
      were recorded simultaneously. RESULTS: Compared with the young, older individuals
      exhibited significantly weakened CMC at all force levels tested. There was a
      proportional relationship between the CMC and EF force and high-positive
      correlation between the CMC and EF strength in both groups. CONCLUSIONS: Weakened
      CMC in aging may be a major factor contributing to age-related muscle weakness,
      and the linear relationship between the CMC and voluntary muscle force suggests
      dependence of force output on translation of the descending command to muscle
      electrical signal.

PMID- 25779097
TI  - Ganoderma lucidum derived ganoderenic acid B reverses ABCB1-mediated multidrug
      resistance in HepG2/ADM cells.
AB  - Chemotherapy is one of the most common therapeutic option for metastatic tumors
      and hematological malignancies. ABCB1-mediated multidrug resistance is the major
      obstacle for chemotherapy. Natural products with diversified structures are ideal
      source of ABCB1 modulators. Ganoderenic acid B, a lanostane-type triterpene
      isolated from Ganoderma lucidum, exhibited potent reversal effect on ABCB1
      mediated multidrug resistance of HepG2/ADM cells to doxorubicin, vincristine and
      paclitaxel. Similarly, ganoderenic acid B could also significantly reverse the
      resistance of ABCB1-overexpressing MCF-7/ADR cells to doxorubicin. Furthermore,
      ganoderenic acid B notably enhanced intracellular accumulation of rhodamine-123
      in HepG2/ADM cells through inhibition of its efflux. ABCB1 siRNA interference
      assay indicated that the reversal activity of ganoderenic acid B was dependent on
      ABCB1. Further mechanistic investigations found that ganoderenic acid B did not
      alter the expression level of ABCB1 and the activity of ABCB1 ATPase. Molecular
      docking model displayed that the positions of ganoderenic acid B binding to ABCB1
      were different from the region of verapamil interacted with ABCB1. Collectively,
      ganoderenic acid B can enhance the cytotoxicity of chemotherapeutics towards
      ABCB1-mediated MDR cancer cells via inhibition of the transport function of
      ABCB1. These findings provide evidence that ganoderenic acid B has the potential
      to be developed into an ABCB1-mediated multidrug resistance reversal agent.

PMID- 25779098
TI  - Evaluation of the use of automatic exposure control and automatic tube potential
      selection in low-dose cerebrospinal fluid shunt head CT.
AB  - INTRODUCTION: Cerebrospinal fluid shunts are primarily used for the treatment of
      hydrocephalus. Shunt complications may necessitate multiple non-contrast head CT
      scans resulting in potentially high levels of radiation dose starting at an early
      age. A new head CT protocol using automatic exposure control and automated tube
      potential selection has been implemented at our institution to reduce radiation
      exposure. The purpose of this study was to evaluate the reduction in radiation
      dose achieved by this protocol compared with a protocol with fixed parameters.
      METHODS: A retrospective sample of 60 non-contrast head CT scans assessing for
      cerebrospinal fluid shunt malfunction was identified, 30 of which were performed
      with each protocol. The radiation doses of the two protocols were compared using
      the volume CT dose index and dose length product. The diagnostic acceptability
      and quality of each scan were evaluated by three independent readers. RESULTS:
      The new protocol lowered the average volume CT dose index from 15.2 to 9.2 mGy
      representing a 39 % reduction (P < 0.01; 95 % CI 35-44 %) and lowered the dose
      length product from 259.5 to 151.2 mGy/cm representing a 42 % reduction (P <
      0.01; 95 % CI 34-50 %). The new protocol produced diagnostically acceptable scans
      with comparable image quality to the fixed parameter protocol. CONCLUSION: A
      pediatric shunt non-contrast head CT protocol using automatic exposure control
      and automated tube potential selection reduced patient radiation dose compared
      with a fixed parameter protocol while producing diagnostic images of comparable
      quality.

PMID- 25779099
TI  - The impact of companion diagnostic device measurement performance on clinical
      validation of personalized medicine.
AB  - A key component of personalized medicine is companion diagnostics that measure
      biomarkers, for example, protein expression, gene amplification or specific
      mutations. Most of the recent attention concerning molecular cancer diagnostics
      has been focused on the biomarkers of response to therapy, such as V-Ki-ras2
      Kirsten rat sarcoma viral oncogene homolog (KRAS) mutations in metastatic
      colorectal cancer, epidermal growth factor receptor mutations in metastatic
      malignant melanoma. The presence or absence of these markers is directly linked
      to the response rates of particular targeted therapies with small-molecule kinase
      inhibitors or antibodies. Therefore, testing for these markers has become a
      critical step in the target therapy of the aforementioned tumors. The core
      capability of personalized medicine is the companion diagnostic devices' (CDx)
      ability to accurately and precisely stratify patients by their likelihood of
      benefit (or harm) from a particular therapy. There is no reference in the
      literature discussing the impact of device's measurement performance, for
      example, analytical accuracy and precision on treatment effects, variances, and
      sample sizes of clinical trial for the personalized medicine. In this paper,
      using both analytical and estimation method, we assessed the impact of CDx
      measurement performance as a function of positive and negative predictive values
      and imprecision (standard deviation) on treatment effects, variances of clinical
      outcome, and sample sizes for the clinical trials.

PMID- 25779100
TI  - The association between diabetes and breast cancer stage at diagnosis: a
      population-based study.
AB  - Women with diabetes have higher breast cancer incidence and mortality. The
      purpose of this study was to examine the impact of diabetes on stage at breast
      cancer diagnosis, as a possible reason for their higher mortality. Using
      population-based health databases from Ontario, Canada, this retrospective cohort
      study examined stage at diagnosis (II, III, or IV vs I) among women aged 20-105
      years who were newly diagnosed with invasive breast cancer between 2007 and 2012.
      We compared those with diabetes to those without diabetes. Diabetes was defined
      based on medical records using a validated algorithm. Among 38,407 women with
      breast cancer, 6115 (15.9 %) women had diabetes. Breast cancer patients with
      diabetes were significantly more likely to present with advanced-stage breast
      cancer than those without diabetes. After adjustment for mammograms and other
      covariates, diabetes was associated with a significantly increased risk of Stage
      II [adjusted odds ratio (aOR) 1.14, 95 % confidence interval (CI) 1.07, 1.22],
      Stage III (aOR 1.21, 95 % CI 1.11, 1.33), and Stage IV (aOR 1.16, 95 % CI 1.01,
      1.33) versus Stage I breast cancer. Women with diabetes had a higher risk of
      lymph node metastases (aOR 1.16, 95 % CI 1.06, 1.27) and tumors with size over 2
      cm (aOR 1.16, 95 % CI 1.06, 1.28). Diabetes was associated with more advanced
      stage breast cancer, even after accounting for differences in screening mammogram
      use and other factors. Our findings suggest that diabetes may predispose to more
      aggressive breast cancer, which may be a contributor to their higher cancer
      mortality.

PMID- 25779101
TI  - High tumor budding stratifies breast cancer with metastatic properties.
AB  - Tumor budding refers to single or small cluster of tumor cells detached from the
      main tumor mass. In colon cancer high tumor budding is associated with positive
      lymph nodes and worse prognosis. Therefore, we investigated the value of tumor
      budding as a predictive feature of lymph node status in breast cancer (BC). Whole
      tissue sections from 148 surgical resection specimens (SRS) and 99 matched
      preoperative core biopsies (CB) with invasive BC of no special type were analyzed
      on one slide stained with pan-cytokeratin. In SRS, the total number of
      intratumoral (ITB) and peripheral tumor buds (PTB) in ten high-power fields (HPF)
      were counted. A bud was defined as a single tumor cell or a cluster of up to five
      tumor cells. High tumor budding equated to scores averaging >4 tumor buds across
      10HPFs. In CB high tumor budding was defined as >=10 buds/HPF. The results were
      correlated with pathological parameters. In SRS high PTB stratified BC with lymph
      node metastases (p <= 0.03) and lymphatic invasion (p <= 0.015). In CB high tumor
      budding was significantly (p = 0.0063) associated with venous invasion.
      Pathologists are able, based on morphology, to categorize BC into a high and low
      risk groups based in part on lymph node status. This risk assessment can be
      easily performed during routine diagnostics and it is time and cost effective.
      These results suggest that high PTB is associated with loco-regional metastasis,
      highlighting the possibility that this tumor feature may help in therapeutic
      decision-making.

PMID- 25779103
TI  - Monitoring treatment outcomes in patients with chronic disease: lessons from
      tuberculosis and HIV/AIDS care and treatment programmes.

PMID- 25779102
TI  - Nested case-control study of selected systemic autoimmune diseases in World Trade
      Center rescue/recovery workers.
AB  - OBJECTIVE: To test the a priori hypothesis that acute and chronic work exposures
      to the World Trade Center (WTC) site on or after September 11, 2001 were
      associated with risk of new-onset systemic autoimmune diseases. METHODS: A nested
      case-control study was performed in WTC rescue/recovery workers who had received
      a rheumatologist-confirmed systemic autoimmune disease diagnosis between
      September 12, 2001 and September 11, 2013 (n = 59), each of whom was individually
      matched to 4 randomly selected controls (n = 236) on the basis of year of hire
      (+/-1 year), sex, race, and work assignment (firefighter or emergency medical
      service). Acute exposure was defined according to the earliest time of arrival
      (morning of 9/11 versus later) at the WTC site, and chronic exposure was defined
      as duration (number of months) of WTC site-related work. Rheumatologists were
      blinded with regard to each subject's exposure status. The conditional odds
      ratios (CORs) with 95% confidence intervals (95% CIs) for incident autoimmune
      disease were derived from exact conditional logistic regression models. RESULTS:
      Rheumatoid arthritis was the most common autoimmune diagnosis (37% of subjects),
      followed by spondyloarthritis (22%), inflammatory myositis (14%), systemic lupus
      erythematosus (12%), systemic sclerosis (5%), Sjogren's syndrome (5%),
      antiphospholipid syndrome (3%), and granulomatosis with polyangiitis (Wegener's)
      (2%). The COR for incident autoimmune disease increased by 13% (COR 1.13, 95% CI
      1.02-1.26) for each additional month worked at the WTC site. These odds were
      independent of the association between high acute exposure (working during the
      morning of 9/11) and disease outcome, which conveyed an elevated, but not
      statistically significant, risk (COR 1.85, 95% CI 0.86-3.89). CONCLUSION:
      Prolonged work at the WTC site, independent of acute exposure, was an important
      predictor of post-9/11 systemic autoimmune diseases. The WTC Health Program
      should expand surveillance efforts for those with extended exposures, as early
      detection can facilitate early treatment, which has been shown to minimize organ
      damage and improve quality of life.

PMID- 25779104
TI  - Multiple Biological Effects of Olive Oil By-products such as Leaves, Stems,
      Flowers, Olive Milled Waste, Fruit Pulp, and Seeds of the Olive Plant on Skin.
AB  - As olive oil production increases, so does the amount of olive oil by-products,
      which can cause environmental problems. Thus, new ways to utilize the by-products
      are needed. In the present study, five bioactive characteristics of olive oil by
      products were assessed, namely their antioxidant, anti-bacterial, anti
      melanogenesis, anti-allergic, and collagen-production-promoting activities.
      First, the extracts of leaves (May and October), stems (May and October),
      flowers, olive milled waste, fruit pulp and seeds were prepared using two safe
      solvents, ethanol and water. According to HPLC and LC/MS analysis and Folin
      Ciocalteu assay, the ethanol extracts of the leaves (May and October), stems (May
      and October) and flowers contained oleuropein, and the ethanol extract of the
      stems showed the highest total phenol content. Oleuropein may contribute to the
      antioxidant and anti-melanogenesis activities of the leaves, stems, and flowers.
      However, other active compounds or synergistic effects present in the ethanol
      extracts are also likely to contribute to the anti-bacterial activity of the
      leaves and flowers, the anti-melanogenesis activity of some parts, the anti
      allergic activity of olive milled waste, and the collagen-production-promoting
      activity of the leaves, stems, olive milled waste and fruit pulp. This study
      provides evidence that the by-products of olive oil have the potential to be
      further developed and used in the skin care industry.

PMID- 25779106
TI  - Multiple antibiotic resistance indexing of Escherichia coli to identify high-risk
      sources of faecal contamination of water.
AB  - We evaluated the antibiogram profile of Escherichia coli (n = 300) isolated from
      selected rivers in Osun State, Nigeria. The identities of the E. coli isolates
      were confirmed by polymerase chain reaction (PCR) technique. Susceptibility of
      the isolates to 20 antibiotics conventionally used in clinical cases was assessed
      in vitro by the standardized agar disc-diffusion method. All the isolates were
      susceptible to imipenem, meropenem, amikacin and gatilofloxacin. The isolates
      were variously susceptible to the other antibiotics as follows: ciprofloxacin (96
      %), kanamycin (95 %), neomycin (92 %), streptomycin (84 %), chloramphenicol (73
      %), nalidixic acid (66 %), nitrofurantoin (64 %), gentamycin (63 %), doxycycline
      (58 %), cefepime (57 %), tetracycline (49 %) and cephalothin (42 %). The multiple
      antibiotic resistance indexing ranged from 0.50 to 0.80 for all the sampling
      locations and exceeded the threshold value of 0.2, suggesting the origin of the
      isolates to be of high antimicrobial usage. Our findings signify an increase in
      the incidence of antimicrobial resistance of E. coli towards conventionally used
      antibiotics necessitating proper surveillance programmes towards the monitoring
      of antimicrobial resistance determinants in water bodies.

PMID- 25779105
TI  - The class II PI 3-kinase, PI3KC2alpha, links platelet internal membrane structure
      to shear-dependent adhesive function.
AB  - PI3KC2alpha is a broadly expressed lipid kinase with critical functions during
      embryonic development but poorly defined roles in adult physiology. Here we
      utilize multiple mouse genetic models to uncover a role for PI3KC2alpha in
      regulating the internal membrane reserve structure of megakaryocytes (demarcation
      membrane system) and platelets (open canalicular system) that results in
      dysregulated platelet adhesion under haemodynamic shear stress. Structural
      alterations in the platelet internal membrane lead to enhanced membrane tether
      formation that is associated with accelerated, yet highly unstable, thrombus
      formation in vitro and in vivo. Notably, agonist-induced 3-phosphorylated
      phosphoinositide production and cellular activation are normal in PI3KC2alpha
      deficient platelets. These findings demonstrate an important role for PI3KC2alpha
      in regulating shear-dependent platelet adhesion via regulation of membrane
      structure, rather than acute signalling. These studies provide a link between the
      open canalicular system and platelet adhesive function that has relevance to the
      primary haemostatic and prothrombotic function of platelets. 

PMID- 25779107
TI  - Estimation of contribution ratios of pollutant sources to a specific section
      based on an enhanced water quality model.
AB  - Because water quality monitoring sections or sites could reflect the water
      quality status of rivers, surface water quality management based on water quality
      monitoring sections or sites would be effective. For the purpose of improving
      water quality of rivers, quantifying the contribution ratios of pollutant
      resources to a specific section is necessary. Because physical and chemical
      processes of nutrient pollutants are complex in water bodies, it is difficult to
      quantitatively compute the contribution ratios. However, water quality models
      have proved to be effective tools to estimate surface water quality. In this
      project, an enhanced QUAL2Kw model with an added module was applied to the
      Xin'anjiang Watershed, to obtain water quality information along the river and to
      assess the contribution ratios of each pollutant source to a certain section (the
      Jiekou state-controlled section). Model validation indicated that the results
      were reliable. Then, contribution ratios were analyzed through the added module.
      Results show that among the pollutant sources, the Lianjiang tributary
      contributes the largest part of total nitrogen (50.43%), total phosphorus
      (45.60%), ammonia nitrogen (32.90%), nitrate (nitrite + nitrate) nitrogen
      (47.73%), and organic nitrogen (37.87%). Furthermore, contribution ratios in
      different reaches varied along the river. Compared with pollutant loads ratios of
      different sources in the watershed, an analysis of contribution ratios of
      pollutant sources for each specific section, which takes the localized chemical
      and physical processes into consideration, was more suitable for local-regional
      water quality management. In summary, this method of analyzing the contribution
      ratios of pollutant sources to a specific section based on the QUAL2Kw model was
      found to support the improvement of the local environment.

PMID- 25779108
TI  - Intercomparison of real-time tailpipe ammonia measurements from vehicles tested
      over the new world-harmonized light-duty vehicle test cycle (WLTC).
AB  - Four light-duty vehicles (two diesel, one flex-fuel, and one gasoline vehicle)
      were tested as part of an intercomparison exercise of the world-harmonized light
      duty vehicle test procedure (WLTP) aiming at measuring real-time ammonia
      emissions from the vehicles' raw exhaust at the tailpipe. The tests were
      conducted in the Vehicle Emission Laboratory (VELA) at the European Commission
      Joint Research Centre (EC-JRC), Ispra, Italy. HORIBA, CGS, and the Sustainable
      Transport Unit of the Joint Research Centre (JRC) took part in the measurement
      and analysis of the four vehicles' exhaust emissions over the world-harmonized
      light-duty vehicle test cycle class 3, version 5.3 using a HORIBA MEXA 1400 QL
      NX, a CGS BLAQ-Sys, and the JRC Fourier transform infrared spectrometer,
      respectively. The measured ammonia concentrations and the emission profiles
      revealed that these three instruments are suitable to measure ammonia from the
      vehicles' raw exhaust, presenting no significant differences. Furthermore,
      results showed that measurement of ammonia from the vehicle exhaust using online
      systems can be performed guaranteeing the reproducibility and repeatability of
      the results. While no ammonia was detected for any of the two diesel vehicles
      (even though, one was equipped with a selective catalytic reduction system), we
      report average ammonia emission factors 8-10 mg/km (average concentrations 20-23
      ppm) and 10-12 mg/km (average concentrations 22-24 ppm) for the flex-fuel and
      gasoline vehicles, respectively.

PMID- 25779109
TI  - Comprehensive studies of hydrogeochemical processes and quality status of
      groundwater with tools of cluster, grouping analysis, and fuzzy set method using
      GIS platform: a case study of Dalcheon in Ulsan City, Korea.
AB  - This research aimed at developing comprehensive assessments of physicochemical
      quality of groundwater for drinking and irrigation purposes at Dalcheon in Ulsan
      City, Korea. The mean concentration of major ions represented as follows: Ca
      (94.3 mg/L) > Mg (41.7 mg/L) > Na (19.2 mg/L) > K (3.2 mg/L) for cations and SO4
      (351 mg/L) > HCO3 (169 mg/L) > Cl (19 mg/L) for anions. Thematic maps for
      physicochemical parameters of groundwater were prepared, classified, weighted,
      and integrated in GIS method with fuzzy logic. The maps exhibited that suitable
      zone of drinking and irrigation purpose occupied in SE, NE, and NW sectors. The
      undesirable zone of drinking purpose was observed in SW and central parts and
      that of irrigation was in the western part of the study area. This was influenced
      by improperly treated effluents from an abandoned iron ore mine, irrigation, and
      domestic fields. By grouping analysis, groundwater types were classified into
      Ca(HCO3)2, (Ca,Mg)Cl2, and CaCl2, and CaHCO3 was the most predominant type.
      Grouping analysis also showed three types of irrigation water such as C1S1, C1S2,
      and C1S3. C1S3 type of high salinity to low sodium hazard was the most dominant
      in the study area. Equilibrium processes elucidated the groundwater samples were
      in the saturated to undersaturated condition with respect to aragonite, calcite,
      dolomite, and gypsum due to precipitation and deposition processes. Cluster
      analysis suggested that high contents of SO4 and HCO3 with low Cl was related
      with water-rock interactions and along with mining impact. This study showed that
      the effluents discharged from mining waste was the main sources of groundwater
      quality deterioration.

PMID- 25779110
TI  - Impact of common cytostatic drugs on pollen fertility in higher plants.
AB  - Cytostatic drugs are among the most toxic chemicals which are produced. Many of
      them cause damage of the genetic material which may affect the fertility of
      higher organisms. To study the impact of the widely used anticancer drugs
      [cisplatin (CisPt), etoposide (Et), and 5-fluorouracil (5-FU)] on the
      reproduction of higher plants, pollen abortion experiments were conducted with
      species which belong to major plant families, namely with Tradescantia paludosa
      (Commelinaceae), Arabidopsis thaliana (Brassicaceae), Chelidonium majus
      (Papaveraceae), and Alisma plantago-aquatica (Alismataceae). All compounds
      increased the frequencies of abortive grains. The lowest effective doses were in
      general in a narrow range (i.e., 1 and 10 mg/kg of dry soil). The effects of the
      individual drugs were similar in T. paludosa, A. plantago-aquatica, and Ch.
      majus, while A. thaliana was consistently less sensitive. The highest abortion
      rate was obtained in most experiments with CisPt, followed by 5-FU and Et.
      Comparisons of the doses which caused effects in the present experiments in the
      different species with the predicted environment concentrations and with the
      levels of the cytostatics which were detected in hospital wastewaters show that
      the realistic environmental concentrations of the drugs are 4-6 orders of
      magnitude lower. Therefore, it is unlikely that these drugs affect the fertility
      of higher plants in aquatic and terrestrial ecosystems. 

PMID- 25779111
TI  - Selenium geochemical distribution in the environment and predicted human daily
      dietary intake in northeastern Qinghai, China.
AB  - Ping'an is a selenium (Se)-rich region located in northeastern Qinghai Province
      of China. To better understand the selenium geochemical distribution and its
      potential ecological effects, this field study investigated the Se distribution
      in the local environment, soil Se bioavailability, and the daily dietary Se
      intake of Ping'an residents. Concentrations of total Se were determined in soil,
      plant, water, and food samples. Results showed that Ping'an is generally a Se
      rich region in China. High-Se soil mainly distributes in the north of
      Hongshuiquan Town in the study region. Se concentration in 43 plant samples
      varied significantly from not detected (nd) to 904 MUg/kg, following a descending
      order of pasture > grain > vegetable > fruit, which was much lower than other
      regions in China. The drinking water Se concentrations were also significantly
      lower than the European and Chinese surface water Se standards of 10 and 50
      MUg/L. The predicted daily dietary Se intake (48 +/- 20 MUg per person) in
      Ping'an met the demand of the WHO-recommended Se amount of 55 MUg per person. The
      Se content is high in soil, but low in different kinds of plants and Se intake,
      indicating that Se that can be taken up by plants was very low. The K2HPO4-KH2PO4
      extractable Se in the soil accounted for only 3% of the total soil Se, indicating
      that a low soil bioavailable Se might result in low Se accumulation in plant
      tissues in Ping'an. This might be due to the influences of geochemistry and the
      inherent properties of the parent materials of these soils. Therefore, further
      studies need to focus on better understanding the process and influential factors
      to soil Se bioavailability to successfully utilize the soil Se resource in low-Se
      availability areas.

PMID- 25779112
TI  - An innovative coupling between column leaching and oxygen consumption tests to
      assess behavior of contaminated marine dredged sediments.
AB  - Contaminated dredged sediments are often considered hazardous wastes, so they
      have to be adequately managed to avoid leaching of pollutants. The mobility of
      inorganic contaminants is a major concern. Metal sulfides (mainly framboidal
      pyrite, copper, and zinc sulfides) have been investigated in this study as an
      important reactive metal-bearing phase sensitive to atmospheric oxygen action. An
      oxygen consumption test (OC-Test) has been adapted to assess the reactivity of
      dredged sediments when exposed to atmospheric oxygen. An experimental column set
      up has been developed allowing the coupling between leaching and oxygen
      consumption test to investigate the reactivity of the sediment. This reactivity,
      which consisted of sulfide oxidation, was found to occur for saturation degree
      between 60 and 90 % and until the 20th testing week, through significant sulfates
      releases. These latter were assumed to come from sulfide oxidation in the first
      step of the test, then probably from gypsum dissolution. Confrontation results of
      OC-Test and leachate quality shows that Cu was well correlated to sulfates
      releases, which in turn, leads to Ca and Mg dissolution (buffer effect). Cu, and
      mostly Zn, was associated to organic matter, phyllosilicates, and other minerals
      through organo-clay complexes. This research confirmed that the OC-Test,
      originally developed for mine tailings, could be a useful tool in the dredged
      sediment field which can allow for intrinsic characterization of reactivity of a
      material suspected to readily reacting with oxygen and for better understanding
      of geochemical processes that affect pollutants behavior, conversion, and
      transfer in the environment.

PMID- 25779113
TI  - Effects of anthracene on filtration rates, antioxidant defense system, and redox
      proteomics in the Mediterranean clam Ruditapes decussatus (Mollusca: Bivalvia).
AB  - This study aimed at analyzing the impact of a toxic polyaromatic hydrocarbon
      (PAH), anthracene (ANT), on Ruditapes decussatus collected from a Tunisian
      coastal lagoon (Bizerte Lagoon). Filtration rates, several antioxidant enzymes-
      superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx),
      glutathione reductase (GR), and glutathione transferase (GST)--as well as indices
      of protein oxidation status were determined in various tissues of this bivalve.
      Specimens were exposed to 100 MUg/L of ANT for 2 days. ANT levels were evaluated
      using HPLC and were detected in the gill and digestive gland at different
      amounts. ANT exposure altered the behavior of bivalves by changing the siphon
      movement and decreasing filtration rate significantly. The enzymatic results
      indicated that ANT exposure affected the oxidative stress status of the gills of
      R. decussatus. In addition, modification of proteins was detected in the gills
      using redox proteomics after ANT treatment. Three protein spots were successfully
      identified by matrix-assisted laser desorption/ionization tandem time-of-flight
      mass spectrometry (MALDI-TOF-MS). These proteins can be roughly related to muscle
      contraction function. In contrast, no significant modification of enzymatic and
      protein responses was detected in the digestive gland after ANT treatment. These
      data demonstrate that combined behavioral and biochemical analyses are a powerful
      tool to provide valuable insights into possible mechanisms of toxicity of
      anthracene in R. decussatus. Additionally, the results highlight the potential of
      the gill as a valuable candidate for investigating PAH toxicity.

PMID- 25779115
TI  - Effect of therapeutic femtosecond laser pulse energy, repetition rate, and
      numerical aperture on laser-induced second and third harmonic generation in
      corneal tissue.
AB  - Clinical therapy incorporating femtosecond laser (FSL) devices is a quickly
      growing field in modern biomedical technology due to their precision and ability
      to generate therapeutic effects with substantially less laser pulse energy. FSLs
      have the potential to produce nonlinear optical effects such as harmonic
      generation (HG), especially in tissues with significant nonlinear
      susceptibilities such as the cornea. HG in corneal tissue has been demonstrated
      in nonlinear harmonic microscopy using low-power FSLs. Furthermore, the
      wavelength ranges of harmonic spectral emissions generated in corneal tissues are
      known to be phototoxic above certain intensities. We have investigated how the
      critical FSL parameters pulse energy, pulse repetition rate, and numerical
      aperture influence both second (SHG) and third harmonic generation (THG) in
      corneal tissue. Experimental results demonstrated corresponding increases in HG
      intensity with increasing repetition rate and numerical aperture. HG duration
      decreased with increasing repetition rate and pulse energy. The data also
      demonstrated a significant difference in HG between FSL parameters representing
      the two most common classes of FSL therapeutic devices.

PMID- 25779204
TI  - Carbamylated low-density lipoprotein attenuates glucose uptake via a nitric oxide
      mediated pathway in rat L6 skeletal muscle cells.
AB  - Carbamylation is a cyanate-mediated posttranslational modification. We previously
      reported that carbamylated low-density lipoprotein (cLDL) increases reactive
      oxygen species and apoptosis via a lectin-like oxidized LDL receptor mediated
      pathway in human umbilical vein endothelial cells. A recent study reported an
      association between cLDL and type 2 diabetes mellitus (T2DM). In the current
      study, the effects of cLDL on glucose transport were explored in skeletal muscle
      cells. The effect of cLDL on glucose uptake, glucose transporter 4 (GLUT4)
      translocation, and signaling pathway were examined in cultured rat L6 muscle
      cells using 2-deoxyglucose uptake, immunofluorescence staining and western blot
      analysis. The quantity of nitric oxide (NO) was evaluated by the Griess reaction.
      The effect of native LDL (nLDL) from patients with chronic renal failure (CRF
      nLDL) on glucose uptake was also determined. It was observed that cLDL
      significantly attenuated glucose uptake and GLUT4 translocation to the membrane,
      which was mediated via the increase in inducible nitric oxide synthase (iNOS)
      induced NO production. Tyrosine nitration of the insulin receptor substrate-1
      (IRS-1) was increased. It was demonstrated that CRF-nLDL markedly reduced glucose
      uptake compared with nLDL from healthy subjects. Collectively, these findings
      indicate that cLDL, alone, attenuates glucose uptake via NO-mediated tyrosine
      nitration of IRS-1 in L6 rat muscle cells and suggests the possibility that cLDL
      is involved in the pathogenesis of T2DM.

PMID- 25779205
TI  - Optically isotropic liquid crystal media formulated by doping star-shaped cyclic
      oligosiloxane liquid crystal surfactants in twin nematic liquid crystals.
AB  - The formation of optically isotropic liquid crystal (LC) media has been
      investigated by doping the star-shaped LC molecular surfactants (SiLC) into the
      rod-shaped twin LC host molecules (DiLC). The experimental phase diagram was
      constructed on the basis of differential scanning calorimetry (DSC) and then a
      theoretical calculation was conducted through a combined Flory-Huggins (FH)/Maier
      Saupe-McMillan (MSM)/phase field (PF) model to account for the experimental
      results. The phase diagram of the SiLC/DiLC mixtures revealed the broad
      coexistence regions such as smectic A + crystal (SmA1 + Cr2), liquid + crystal
      (L1 + Cr2), and liquid + nematic (L1 + N2) at the intermediate composition along
      with the narrow single phase crystal (Cr2), smectic (SmA1), and nematic (N2)
      regions. The morphologies and structures of these coexistence regions were
      further confirmed by polarized optical microscopy (POM) and wide-angle X-ray
      diffraction (WAXD). At the 80/20 SiLC/DiLC composition, the optical anisotropy
      was induced under an alternating current (AC) electric field above its
      isotropization temperature. The formation of an optically isotropic LC medium in
      mixtures of the SiLC molecular surfactants and nematic LC host may allow us to
      develop new electro-optical devices. 

PMID- 25779206
TI  - Localization of CD9 Molecule on Bull Spermatozoa: Its Involvement in the Sperm
      Egg Interaction.
AB  - Tetraspanin CD9 is one of the egg membrane proteins known to be essential in
      fertilization process. The presence and localization of CD9 molecule in
      spermatozoa and its possible function in reproduction are still unclear. In our
      study, we describe the localization of CD9 on bull spermatozoa. In the
      immunofluorescence assay, the positive signal has been observed in the high
      proportion of sperm cells as a fine grains either on the apical part or through
      the entire anterior region of sperm head. CD9 recognized by monoclonal antibody
      IVA-50 was detected on freshly ejaculated (83.4 +/- 3.7%) and frozen-thawed (84.3
      +/- 2.3%) sperm. The same reaction pattern was observed on sperm capacitated for
      1 h, 2 h, 3 h and 4 h (83.6 +/- 2.0%; 84.0 +/- 1.5%; 85.7 +/- 0.8%; 77.5 +/-
      10.8%). The presence of CD9 exclusively on plasma membrane of the bovine sperm
      has been detected by Western blot analysis of the protein fractions after the
      discontinuous sucrose gradient fractionation of the bull sperm. Moreover,
      probable role of the sperm CD9 molecule in fertilization process of cattle has
      been suggested as sperm treatment with anti-CD9 antibody significantly reduced
      (by 25%, p <= 0.001) the number of fertilized oocytes compared to control group
      in fertilization assay in vitro. 

PMID- 25779207
TI  - Shifts in the metabolic function of a benthic estuarine microbial community
      following a single pulse exposure to silver nanoparticles.
AB  - The increasing use of silver nanoparticles (AgNPs) as a biocidal agent and their
      potential accumulation in sediments may threaten non-target natural environmental
      bacterial communities. In this study a microcosm approach was established to
      investigate the effects of well characterized OECD AgNPs (NM-300) on the function
      of the bacterial community inhabiting marine estuarine sediments (salinity
      310/00). The results showed that a single pulse of NM-300 AgNPs (1 mg L(-1)) that
      led to sediment concentrations below 6 mg Ag kg(-1) dry weight inhibited the
      bacterial utilization of environmentally relevant carbon substrates. As a result,
      the functional diversity changed, but recovered after 120 h under the
      experimental conditions. This microcosm study suggests that AgNPs under
      environmentally relevant experimental conditions can negatively affect bacterial
      function and provides an insight into the understanding of the bacterial
      community response and resilience to AgNPs exposure, important for informing
      relevant regulatory measures. 

PMID- 25779208
TI  - In situ investigation of the mechanisms of the transport to tissues of polycyclic
      aromatic hydrocarbons adsorbed onto the root surface of Kandelia obovata
      seedlings.
AB  - A novel method for in situ determination of the polycyclic aromatic hydrocarbons
      (PAHs) adsorbed onto the root surface of Kandelia obovata seedlings was
      established using laser-induced time-resolved nanosecond fluorescence
      spectroscopy (LITRF). The linear dynamic ranges for the established method were
      1.5-1240ng/spot for phenanthrene, 1.0-1360ng/spot for pyrene and 5.0-1220ng/spot
      for benzo[a]pyrene. Then, the mechanisms of PAHs transport from the Ko root
      surface to tissues were investigated. The three-phase model including fast, slow
      and very slow fractions was superior to the single or dual-phase model to
      describe the PAHs transport processes. Moreover, the fast fraction of PAHs
      transport process was mainly due to passive movement, while the slow and very
      slow fractions were not. Passive movement was the main process of B[a]P adsorbed
      onto Ko root surface transport to tissues. In addition, the extent of the PAHs
      transport to Ko root tissues at different salinity were evaluated. 

PMID- 25779209
TI  - Antibiotic prevention of postcataract endophthalmitis: a systematic review and
      meta-analysis.
AB  - Endophthalmitis is one of the most feared complications after cataract surgery.
      The aim of this systematic review was to evaluate the effect of intracameral and
      topical antibiotics on the prevention of endophthalmitis after cataract surgery.
      A systematic literature review in the MEDLINE, CINAHL, Cochrane Library and
      EMBASE databases revealed one randomized trial and 17 observational studies
      concerning the prophylactic effect of intracameral antibiotic administration on
      the rate of endophthalmitis after cataract surgery. The effect of topical
      antibiotics on endophthalmitis rate was reported by one randomized trial and one
      observational study. The quality and design of the included studies were analysed
      using the Cochrane risk of bias tool. The quality of the evidence was evaluated
      using the GRADE approach. We found high-to-moderate quality evidence for a marked
      reduction in the risk of endophthalmitis with the use of intracameral antibiotic
      administration of cefazolin, cefuroxime and moxifloxacin, whereas no effect was
      found with the use of topical antibiotics or intracameral vancomycin.
      Endophthalmitis occurred on average in one of 2855 surgeries when intracameral
      antibiotics were used compared to one of 485 surgeries when intracameral
      antibiotics were not used. The relative risk (95% CI) of endophthalmitis was
      reduced to 0.12 (0.08; 0.18) when intracameral antibiotics were used. The
      difference was highly significant (p < 0.00001). Intracameral antibiotic therapy
      is the best choice for preventing endophthalmitis after cataract surgery. We did
      not find evidence to conclude that topical antibiotic therapy prevents
      endophthalmitis.

PMID- 25779210
TI  - Using temporal orientation, category fluency, and word recall for detecting
      cognitive impairment: the 10-point cognitive screener (10-CS).
AB  - OBJECTIVES: A screening strategy composed of three-item temporal orientation and
      three-word recall has been increasingly used for detecting cognitive impairment.
      However, the intervening task administered between presentation and recall has
      varied. We evaluated six brief tasks that could be useful as intervening
      distractors and possibly provide incremental accuracy: serial subtraction, clock
      drawing, category fluency, letter fluency, timed visual detection, and digits
      backwards. METHODS: Older adults (n = 230) consecutively referred for suspected
      cognitive impairment underwent a comprehensive assessment for gold-standard
      diagnosis, of whom 56 (24%) presented cognitive impairment not dementia and 68
      (30%) presented dementia. Among those with dementia, 87% presented very mild or
      mild stages (Clinical Dementia Rating 0.5 or 1). The incremental value of each
      candidate intervening task in a model already containing orientation and word
      recall was assessed. RESULTS: Category fluency (animal naming) presented the
      highest incremental value among the six candidate intervening tasks.
      Reclassification analyses revealed a net gain of 12% among cognitively impaired
      and 17% among normal participants. A four-point scaled score of the animal naming
      task was added to three-item temporal orientation and three-word recall to
      compose the 10-point Cognitive Screener. The education-adjusted 10-point
      Cognitive Screener outperformed the longer Mini-Mental State Examination for
      detecting both cognitive impairment (area under the curve 0.85 vs 0.77; p =
      0.027) and dementia (area under the curve 0.90 vs 0.83; p = 0.015). CONCLUSIONS:
      Based on empirical data, we have developed a brief and easy-to-use screening
      strategy with higher accuracy and some practical advantages compared with
      commonly used tools.

PMID- 25779211
TI  - Postoperative infection risk after splenectomy: A prospective cohort study.
AB  - INTRODUCTION: Splenectomy is associated with a life-long risk for overwhelming
      infections. The risk for early post-operative infectious complications following
      traumatic and elective splenectomy is, however, understudied. This investigation
      aimed to determine if splenectomy increases the risk for post-operative
      infections. METHODS: This was a retrospective review of prospectively collected
      data on patients admitted to the surgical intensive care unit (SICU) between
      1/2011 and 7/2013 investigating the risk for infectious complications in patients
      undergoing a splenectomy compared with those undergoing any other abdominal
      surgery. RESULTS: During the 30-month study period, a total of 1884 patients were
      admitted to the SICU. Of those, 33 (2%) had a splenectomy and 493 (26%) had an
      abdominal surgery. The two groups were well balanced for age, APACHE IV score
      >20, and past medical history, including diabetes mellitus, cardiac history,
      renal failure or immunosuppression. Patients undergoing splenectomy were more
      likely to have sustained a traumatic injury (30% vs. 7%, p < 0.01). After
      adjustment, splenectomy was associated with increased risk for infectious
      complications (49% vs. 29%, Adjusted Odds Ratio (AOR) [95% CI]: 2.7 [1.3, 5.6], p
      = 0.01), including intra-abdominal abscess (9% vs. 3%, AOR [95% CI]: 4.3 [1.1,
      16.2], p = 0.03). On a subgroup analysis, there were no differences between
      traumatic and elective splenectomy with regards to overall infectious
      complications (50% vs. 46%, p = 0.84), although, abdominal abscess developed only
      in those who had an elective splenectomy (0% vs. 12%, p = 0.55). CONCLUSION:
      Splenectomy increases the risk for post-operative infectious complications.
      Further studies identifying strategies to decrease the associated morbidity are
      necessary.

PMID- 25779212
TI  - Pancreaticoduodenectomy in the presence of a common hepatic artery originating
      from the superior mesenteric artery. Technical implications.
AB  - Pancreaticoduodenectomy (PD) is considered a technically demanding task. Anatomic
      variations in duodenopancreatic vascularization [celiac axis and the superior
      mesenteric artery (SMA)] may carry a risk of potentially life-threatening
      vascular injury. We retrospectively report a modified PD technique performed in
      two patients presenting with a Common Hepatic Artery (CHA) originating from SMA.
      The CHA anatomical pattern was known prior surgical procedure. The main
      modification consisted in cutting pancreas prior dividing the CHA and the
      gastroduodenal artery. No intraoperative incident was reported. Perioperative
      outcomes were unremarkable, no vascular injury or hepatic ischemia was reported.
      Surgeons planning a PD must analyze in depth imaging (CT-scan with 3D
      angiography) and try to find these patterns. Furthermore, some rare arterial
      variations may be met and change typical surgical plan. Knowing prior procedure
      the arterial pattern and keeping in mind expendable or vital vessels allow to
      accomplish unusual but effective operations. 

PMID- 25779213
TI  - Limited utility of inflammatory markers in the early detection of postoperative
      inflammatory complications after pancreatic resection: Cohort study and meta
      analyses.
AB  - PURPOSE: To examine the diagnostic accuracy of systemic inflammatory markers in
      early prediction of inflammatory postoperative complications (IPC) and clinically
      relevant pancreatic fistula (PF). METHODS: Preoperative and postoperative [until
      postoperative day (POD) 4)] measurements of hemoglobin, white blood cell counts
      (WBC), neutrophil/lymphocyte ratio (NLR) and C-reactive protein (CRP) were
      correlated with IPC and PF. Meta-analyses of biochemical predictors were
      performed. RESULTS: Ninety-two out of 378 patients developed IPC, PF occurred in
      31. Preoperative WBC (OR 1.0001, 95% CI: 1.0001-1.0002, p = 0.02), NLR on POD2
      (OR 1.05, 95% CI: 1.006-1.1, p = 0.02) and CRP on POD4 (OR 1.006, 95% CI: 1.002
      1.01, p = 0.02) predicted IPC at multivariate analysis. The model including these
      three variables showed a diagnostic accuracy of 76.8% (sensitivity 20,
      specificity 97%.14; PPV 71.43, PPN 77.27) and, at logistic regression analysis an
      OR of 8.5 (95% CI: 2.5-28.6, p < 0.001). Only CRP >272 on POD3 (OR 3.32, 95% CI:
      1.46-7.52, p = 0.003) was associated with PF with a diagnostic accuracy of 74%
      (sensitivity 54.5, specificity 78.5; PPV 16.88, NPV 94.25). Meta-analyses of
      available data suggested sensitivity of 75.3% (95% CI 66.7-82.6) and specificity
      of 75.5% (95% CI 61.3-85.7). However, these studies were significantly
      heterogeneous. CONCLUSIONS: Readily available, routine tests have limited utility
      in predicting IPC. Further research is required to develop novel biomarkers to
      aid management of these patients.

PMID- 25779214
TI  - A narrative review of evidence for the provision of memory services.
AB  - BACKGROUND: One common finding in analyses of health systems with respect to
      dementia is that there is a "diagnosis gap" in dementia with less than a half of
      those with dementia ever attracting a diagnosis of dementia. The service response
      to this has been to develop memory clinics and other services to enable good
      quality diagnosis of the syndrome of dementia and its sub-types. METHODS: This
      narrative review considers who memory assessment services are for and what they
      should aim to achieve. We will consider the evidence base and discuss "what good
      looks like." RESULTS: The sparsity of the evidence base for the provision of
      memory services is striking. There is a lack of studies that have evaluated the
      absolute and relative impact of different models of diagnostic services or the
      impact of diagnosis and stage of illness at diagnosis. CONCLUSIONS: There remains
      genuine uncertainly about: the positive and negative impacts of receiving the
      diagnosis of dementia; the effects of receiving the diagnosis of dementia at an
      earlier or later stage; and how best to provide memory assessment services in
      terms of clinical and cost-effectiveness. We need applied health research
      designed to fill these important evidence gaps, resolving uncertainty, and
      allowing the development and delivery of efficient and effective services and
      policy to enable people to live well with dementia. The methodology that will be
      needed will be a challenge since, due to ethical and practical considerations, it
      is likely to have to be observational rather than experimental.

PMID- 25779215
TI  - Using QCM-D to study the adhesion of human gingival fibroblasts on implant
      surfaces.
AB  - Sealing the soft tissue-implant interface is one of the key issues in preventing
      transcutaneous implant-associated infections. A promising surface modification
      for improving osseointegration and possibly soft tissue integration is to coat
      the implant surface with hydroxyapatite (HA) nanoparticles. When new implant
      materials are developed, their ability to facilitate cell attachment and
      spreading are commonly investigated in vitro to establish their potential for
      good in vivo performance. However, commonly used techniques, such as microscopy
      methods, are time consuming, invasive, and subjective. This is the first study
      using quartz crystal microbalance with dissipation monitoring, where the real
      time adhesion of biopsy-derived human gingival fibroblasts onto titanium and
      nanostructured HA was investigated. Experiments were performed for at least 16 h,
      and we found that cellular attachment and spreading kinetics can be followed in
      situ by observing the change in dissipation and frequency with time.
      Interestingly, a correlation between cell coverage and the magnitude of
      dissipation shift reached at the end of the experiment was found, but no such
      trend was observed for the frequency. Furthermore, the level of cell coverage was
      found to influence the cellular attachment and spreading behavior. No difference
      in cell response to the two surface types, Ti and nanostructured HA, was found.

PMID- 25779216
TI  - Apparent discrimination in the provision of biologic therapy to patients with
      Crohn's disease according to ethnicity.
AB  - OBJECTIVES: The objective of the study was to investigate whether patients from a
      South Asian ethnic background who had Crohn's disease received equivalent access
      to therapy with biologics compared to patients with an English background. STUDY
      DESIGN: The study was retrospective and covered the period 2008 to 2012. It was
      based on a register of all patients with Crohn's disease in Leicestershire who
      are treated with biologics. The prevalence of Crohn's disease in Leicestershire
      amongst South Asian and English patients was known from earlier studies and from
      these data it was possible to make corrections to allow for the difference in
      frequency of the condition between the two communities. METHODS: All adult
      patients who received biologics for treatment of Crohn's disease in
      Leicestershire between 2008 and 2012 were reviewed and their gender and ethnicity
      noted as well as whether they had received infliximab or adalumimab. The expected
      numbers of patients who should have received these therapies were calculated in
      two ways: RESULTS: One hundred and twenty six patients with Crohn's disease who
      received treatment with biologics were European and 13 South Asian. The patients'
      gender was also noted and 67 European patients (53%) were female as were six
      Asians (46%). Based on prevalence data, the expected distribution of the
      treatment would have been for 97 of the patients to have been European and 42 to
      have been South Asian. If 126 European patients warranted treatment, on this
      basis the expected number of South Asian patients in need of biologic therapy
      would have been 55. Based on the smaller predicted number of South Asian patients
      (42) the difference is significant at P < 0.0001 [Proportion difference=0.69 (95%
      confidence interval=0.539278-0.809576]. For the difference to be extinguished the
      number of English patients who should have received biologic therapy would have
      been as low as between 30 and 39 cases (based on the calculated proportion of 97
      and the actual figure of 126 European patients respectively). Based on a
      population composition, rather than prevalence data, in which 24% of the
      Leicester community should have been of South Asian origin, 33 patients would
      have received biologics compared with 92 patients of English origin (66%). This
      is significantly different to the 13 patients who did receive treatment (z=-3.2,
      P < 0.001). CONCLUSIONS: Suggested reasons for these differences have included
      concerns about the animal origins of infliximab as well as difficulties
      associated with accessing the service, such as the provision of information in an
      appropriate language through appropriate media. For those who come from groups
      with significant social deprivation there is often a readiness to accept more
      limited clinical services. However, such differences themselves, are examples of
      discrimination in clinical practice.

PMID- 25779217
TI  - Personal viewpoint: Limiting maximum ultrafiltration rate as a potential new
      measure of dialysis adequacy.
AB  - While the solute clearance marker (Kt/Vurea ) is widely used, no effective marker
      for volume management exists. Two principles apply to acute volume change in
      hemodialysis: (1) the plasma refill rate, the maximum rate the extracellular
      fluid can replace a contracting intravascular volume (+/-5 mL/kg/hour) and (2)
      the rate of intravascular volume contraction where coronary hypoperfusion,
      myocardial stun, and vascular risk escalates (observed at >=10 mL/kg/hour). In
      extended hour and higher frequency hemodialysis, intravascular contraction rates
      are usually equilibrated by the plasma refill rate, but in "conventional" in
      center hemodialysis, volume contraction rates commonly exceed the capabilities of
      the plasma refill rate, resulting in inevitable hypovolemia. To minimize
      cardiovascular risk, fluid removal rates should ideally be <=10 mL/kg/hour,
      acknowledging that this may be challenging in the in-center setting. Two options
      exist to limit volume removal to >10 mL/kg/hour: restricting interdialytic weight
      gain (always conflict-fraught, often unachievable) or extending sessional
      duration to allow additional removal time. Just as Kt/Vurea quantifies solute
      removal, a simple-to-apply rate variable should also apply for volume removal. As
      predialysis and target postdialysis weights are both known, a simple measure--a
      maximum rate for ultrafiltration (UFRmax )--would advise the sessional duration
      (T) required to minimize organ stun by removing the required fluid load (V) from
      any patient of predialysis weight (W). This would ensure a removal rate no
      greater than 10 mL/kg/hour-T (hours) = V (mL)/10 * W (kg). Used together,
      Kt/Vurea and UFRmax would form a solute and volume composite, each dialysis
      treatment continuing until both solute and volume requirements are fulfilled.

PMID- 25779218
TI  - What is the role of human papillomavirus testing in head and neck cancer?

PMID- 25779219
TI  - Colorimetric and Fluorescent Bimodal Ratiometric Probes for pH Sensing of Living
      Cells.
AB  - pH measurement is widely used in many fields. Ratiometric pH sensing is an
      important way to improve the detection accuracy. Herein, five water-soluble
      cationic porphyrin derivatives were synthesized and their optical property
      changes with pH value were investigated. Their pH-dependent assembly/disassembly
      behaviors caused significant changes in both absorption and fluorescence spectra,
      thus making them promising bimodal ratiometric probes for both colorimetric and
      fluorescent pH sensing. Different substituent identity and position confer these
      probes with different sensitive pH-sensing ranges, and the substituent position
      gives a larger effect. By selecting different porphyrins, different signal
      intensity ratios and different fluorescence excitation wavelengths, sensitive pH
      sensing can be achieved in the range of 2.1-8.0. Having demonstrated the
      excellent reversibility, good accuracy and low cytotoxicity of the probes, they
      were successfully applied in pH sensing inside living cells. 

PMID- 25779221
TI  - Investigation of insecticide-resistance status of Cydia pomonella in Chinese
      populations.
AB  - The codling moth Cydia pomonella (L.) is an economically important fruit pest and
      it has been directly targeted by insecticides worldwide. Serious resistance to
      insecticides has been reported in many countries. As one of the most serious
      invasive pest, the codling moth has populated several areas in China. However,
      resistance to insecticides has not been reported in China. We investigated the
      insecticide-resistance status of four field populations from Northwestern China
      by applying bioassays, enzyme activities, and mutation detections. Diagnostic
      concentrations of lambda-cyhalothrin, chlorpyrifos-ethyl, carbaryl, and
      imidacloprid were determined and used in bioassays. Field populations were less
      susceptible to chlorpyrifos-ethyl and carbaryl than laboratory strain.
      Insensitive populations displayed an elevated glutathione S-transferases (GSTs)
      activity. Reduced carboxylesterase (CarE) activity was observed in some
      insecticide insensitive populations and reduced acetylcholinesterase activity was
      observed only in the Wuw population. The cytochrome P450 polysubstrate
      monooxygenases activities in four field populations were not found to be
      different from susceptible strains. Neither the known-resistance mutation F399V
      in the acetylcholinesterase (AChE) gene, ace1, nor mutations in CarE gene CpCE-1
      were found in adult individuals from our field populations. Native-PAGE revealed
      that various CarE isozymes and AChE insensitivity were occurring among Chinese
      populations. Our results indicate that codling moth populations from Northwestern
      China were insensitivity to chlorpyrifos-ethyl and carbaryl. Increased GST
      activity was responsible for insecticides insensitivity. Decreased CarE activity,
      as well as the presence of CarE and AChE polymorphisms might also be involved in
      insecticides insensitivity. New management strategies for managing this pest are
      discussed. 

PMID- 25779222
TI  - A prospective study of anxiety in ICD patients with a pilot randomized controlled
      trial of cognitive behavioral therapy for patients with moderate to severe
      anxiety.
AB  - PURPOSE: Stress and anxiety are potential consequences from arrhythmias and
      implantable cardioverter defibrillator (ICD) shocks that can contribute to
      substantial morbidity. We assessed anxiety associated with an ICD and whether
      cognitive behavioral therapy (CBT) reduces anxiety. METHODS: The study consisted
      of two parts: part 1 (N = 690) was a prospective cross-sectional observational
      study of consecutive ICD patients. Patients completed the Beck Anxiety Inventory
      (BAI), Generalized Anxiety Disorder Scale (GAD-7), Florida Shock Anxiety Scale
      (FSAS), and Florida Patient Acceptance Survey (FPAS) psychometric tests. Part 2
      (N = 29) was a pilot randomized controlled trial of CBT (three sessions in 3
      months) vs. usual care (UC) in patients with BAI >= 19 from part 1. RESULTS: The
      median BAI and GAD-7 scores were 5 and 2, respectively. By BAI scores, 64.5 % had
      minimal and 3.9 % had severe anxiety. By GAD-7 scores, 73.0 % had low probability
      of anxiety and 2.9 % had high anxiety. Higher anxiety levels were associated with
      recent (p = 0.017) and total number of shocks (p = 0.002). Any shock was
      associated with fear about shocks (FSAS, p < 0.001) and reduced patient ICD
      acceptance (FPAS, p = 0.019). In the pilot trial of CBT, median BAI scores
      decreased from 24.5 to 11 at 1 year (p = 0.031) in the CBT group and GAD-7 scores
      from 12.5 to 7 (p = 0.063); no significant changes in anxiety scores were
      observed in the UC group. CONCLUSIONS: Severe anxiety was present in a small
      proportion of ICD patients, but higher anxiety was associated with recent and
      total number of shocks. The small pilot study suggested that a simple program of
      CBT might lower moderate-high anxiety with lasting effects to 1 year and supports
      the need for a larger trial to validate these results. CLINICAL TRIAL
      REGISTRATION: ClinicalTrials.gov identifier: NCT00851071. URL:
      http://clinicaltrials.gov/ct2/show/NCT00851071?term=anxiety+in+icd+patients+cleve
      and+clinic&rank=1.

PMID- 25779223
TI  - Technical prerequisites and imaging protocols for dynamic and dual energy
      myocardial perfusion imaging.
AB  - Coronary CT angiography (CCTA) is an established imaging technique used for the
      non-invasive morphological assessment of coronary artery disease. As in invasive
      coronary angiography, CCTA anatomical assessment of coronary stenosis does not
      adequately predict hemodynamic relevance. However, recent technical improvements
      provide the possibility of CT myocardial perfusion imaging (CTMPI). Two distinct
      CT techniques are currently available for myocardial perfusion assessment: static
      CT myocardial perfusion imaging (sCTMPI), with single- or dual-energy modality,
      and dynamic CT myocardial perfusion imaging (dCTMPI). The combination of CCTA
      morphological assessment and CTMPI functional evaluation holds promise for
      achieving a comprehensive assessment of coronary artery anatomy and myocardial
      perfusion using a single image modality. 

PMID- 25779224
TI  - Modulation of tumor cell migration, invasion and cell-matrix adhesion by human
      monopolar spindle-one-binder 2.
AB  - Human monopolar spindle-one-binder 2 (hMOB2) is a member of the hMOB family of
      proteins, and it has been reported to regulate the nuclear-Dbf2-related kinase
      (NDR) activation. However, the function of hMOB2 expression in tumor cell
      adhesion and motility has not been addressed. Herein, the lentiviral-mediated
      overexpression and the knockdown of hMOB2 in HepG2 and SMMC-7721 cells was
      established. It was demonstrated that overexpression of hMOB2 significantly
      reduced the cell motility and enhanced the cell-matrix adhesion, while the hMOB2
      knockdown decreased not only the cell motility, but also the cell-matrix
      adhesion. Immunofluorescence results showed that both hMOB2 overexpression and
      knockdown altered assembly of the focal adhesions and the actin cytoskeleton
      rearrangement. Furthermore, the focal adhesion kinase (FAK)-Src-paxillin signal
      pathway activated by hMOB2 was confirmed to be involved in controlling the cell
      motility and the cell-matrix adhesion. These results demonstrated that the
      altered cell-matrix adhesion and cell motility induced by hMOB2 expression was
      caused by the assembly of focal adhesions as well as the actin cytoskeleton
      rearrangement through the activation of the FAK-Src-paxillin signal pathway,
      unveiling a novel mechanism of cell motility and cell-matrix adhesion regulation
      induced by hMOB2 expression. 

PMID- 25779225
TI  - The anticonvulsant retigabine is a subtype selective modulator of GABAA
      receptors.
AB  - OBJECTIVE: Within its range of therapeutic plasma concentrations, the
      anticonvulsant retigabine (ezogabine) is believed to selectively act on Kv7
      channels. Here, the contribution of specific gamma-aminobutyric acid (GABA)A
      receptor subtypes to the antiseizure effects of retigabine was investigated.
      METHODS: Using patch-clamp recordings, seizure-like activity, tonic currents, and
      GABA-induced currents in hippocampal neurons were tested for their sensitivity
      toward retigabine, as were recombinant GABAA receptors expressed in tsA 201
      cells. RESULTS: Retigabine reduced seizure-like activity elicited by low Mg(2+)
      in a concentration-dependent manner with half maximal inhibition at 1 MUm.
      Seizure-like activity triggered by blocking either Kv7 channels or GABAA
      receptors was equally reduced by retigabine, but when these channels/receptors
      were blocked simultaneously, the inhibition was lost. Retigabine (10 MUm)
      enhanced bicuculline-sensitive tonic currents in hippocampal neurons, but failed
      to affect GABA-evoked currents. However, when receptors involved in phasic
      GABAergic inhibition were blocked by penicillin, retigabine did enhance GABA
      evoked currents. In tsA 201 cells expressing various combinations of GABAA
      receptor subunits, 10 MUm retigabine enhanced currents through alpha1beta2delta,
      alpha4beta2delta, alpha4beta3delta, and alpha6beta2delta receptors, but left
      currents through alpha1beta2gamma2S, alpha4beta3gamma2S, alpha5beta3gamma2S, and
      alpha6beta2gamma2S receptors unaltered. With alphabeta receptors, retigabine
      diminished currents through alpha1beta2 and alpha4beta3, but increased currents
      through alpha6beta2 receptors. The enhancement of currents through
      alpha1beta2delta receptors by retigabine was concentration dependent and became
      significant at 1 MUm. SIGNIFICANCE: These results demonstrate that retigabine is
      a subtype selective modulator of GABAA receptors with preference for
      extrasynaptic delta-containing receptors; this property may contribute to its
      broad antiepileptic effectiveness and explain its lack of effect on absence
      seizures.

PMID- 25779226
TI  - Clinical outcomes and graft characteristics in pediatric hematopoietic stem cell
      transplantation: Effect of granulocyte-colony stimulating factor priming.
AB  - In this study, we aimed to determine the effect(s) of G-CSF priming on graft and
      transplantation parameters and compare these findings with those obtained without
      priming. A total of 64 pediatric patients transplanted from HLA-matched family
      donors were enrolled in the study. Twenty-nine patients received G-CSF primed
      marrow (G-BM group) and 35 patients received steady state bone marrow (S-BM
      group). Number of total nucleated cells (TNC) and CD34(+) cells, CFU-GM colony
      number, neutrophil and platelet engraftment times, total length of stay in
      hospital, overall and disease free survival, and occasions of acute and chronic
      GvHD has been compared between these two groups. Granulocyte colony stimulating
      factor primed bone marrow (G-BM) yielded higher numbers of CD34(+) cells, TNCs,
      and CFU-GM colony numbers compared to those obtained in S-BM. The neutrophil
      engraftment time, platelet engraftment time, length of stay in hospital, overall
      survival and disease free survival were not different between G-BM and S-BM
      groups. Also the cumulative incidence of grades II-IV acute and chronic GvHD were
      similar. It was observed that the use of G-CSF did not increase the risk of acute
      or chronic GvHD. We concluded that use of G-CSF for stem cell mobilization is an
      effective and safe method in children. 

PMID- 25779227
TI  - The use of the needle-free jet injection system with buffered lidocaine device
      does not change intravenous placement success in children in the emergency
      department.
AB  - OBJECTIVES: The needle-free jet injection system with buffered lidocaine (J tip)
      has been shown to reduce pain for intravenous (IV) line insertion, but its
      relationship with successful IV placement has not been well studied. This study
      aimed to determine if J tip use is associated with improved first-attempt IV
      placement success in children. METHODS: This was a retrospective cohort study of
      children ages 1 to 18 years with need for emergent IV placement. Approximately
      300 children were selected from each of three separate age groups: 1 to 2, 3 to
      6, and 7 to 18 years. The standard treatment group (no device) included children
      with IV insertions from January 2009 through January 2010 with no J tip. The J
      tip treatment group (device) included children with IV insertions from December
      2010 through December 2011 who received J tips. Successful IV placement on first
      attempt was the primary outcome. A chi-square test was used to compare the
      proportion of first-attempt success and logistic regression was performed to
      assess the effect of device use and patient age, sex, and race on first-attempt
      success. RESULTS: A total of 958 children were identified, 501 in the no-device
      group and 457 in the device group. The most common diagnoses were vomiting or
      dehydration (30.3%), trauma or burn (20.0%), and infection (15.5%). Overall,
      first-attempt success was 69.0% and was similar between the no-device (68.7%) and
      device (69.4%) groups (p = 0.81). No difference in first-attempt success with the
      use of the device was found in any of the age groups. Multivariate analysis found
      that only age of 1 to 2 years was associated with lower odds of first-attempt
      success when controlling for patient characteristics and device use. CONCLUSIONS:
      The use of the J tip did not affect first-attempt success for IV placement in
      children.

PMID- 25779305
TI  - Familial colorectal cancer syndromes: an overview of clinical management.
AB  - Familial colorectal cancer syndromes pose a complex challenge to the treating
      clinician. Once a syndrome is recognized, genetic testing is often required to
      confirm the clinical suspicion. Management from that point is usually based on
      disease-specific guideline recommendations targeting risk reduction for the
      patient and their relatives through surgery, surveillance and chemoprophylaxis.
      The aim of this paper is to provide an up-to-date summary of the most common
      familial syndromes and their medical and surgical management, with specific
      emphasis on evidence-based interventions that improve patient outcome, and to
      present the information in a manner that is easily readable and clinically
      relevant to the treating clinician. 

PMID- 25779306
TI  - Explaining the power-law distribution of human mobility through transportation
      modality decomposition.
AB  - Human mobility has been empirically observed to exhibit Levy flight
      characteristics and behaviour with power-law distributed jump size. The
      fundamental mechanisms behind this behaviour has not yet been fully explained. In
      this paper, we propose to explain the Levy walk behaviour observed in human
      mobility patterns by decomposing them into different classes according to the
      different transportation modes, such as Walk/Run, Bike, Train/Subway or
      Car/Taxi/Bus. Our analysis is based on two real-life GPS datasets containing
      approximately 10 and 20 million GPS samples with transportation mode information.
      We show that human mobility can be modelled as a mixture of different
      transportation modes, and that these single movement patterns can be approximated
      by a lognormal distribution rather than a power-law distribution. Then, we
      demonstrate that the mixture of the decomposed lognormal flight distributions
      associated with each modality is a power-law distribution, providing an
      explanation to the emergence of Levy Walk patterns that characterize human
      mobility patterns. 

PMID- 25779307
TI  - Whole-genome sequencing for comparative genomics and de novo genome assembly.
AB  - Next-generation sequencing technologies for whole-genome sequencing of
      mycobacteria are rapidly becoming an attractive alternative to more traditional
      sequencing methods. In particular this technology is proving useful for genome
      wide identification of mutations in mycobacteria (comparative genomics) as well
      as for de novo assembly of whole genomes. Next-generation sequencing however
      generates a vast quantity of data that can only be transformed into a usable and
      comprehensible form using bioinformatics. Here we describe the methodology one
      would use to prepare libraries for whole-genome sequencing, and the basic
      bioinformatics to identify mutations in a genome following Illumina HiSeq or
      MiSeq sequencing, as well as de novo genome assembly following sequencing using
      Pacific Biosciences (PacBio). 

PMID- 25779308
TI  - Whole-transcriptome sequencing for high-resolution transcriptomic analysis in
      Mycobacterium tuberculosis.
AB  - RNA-seq uses next-generation sequencing technology to determine the transcription
      profile of an organism in a quantitative manner. With respect to microarrays,
      this methodology allows greater resolution, increased dynamic range, and
      identification of new features such as previously unannotated genes and noncoding
      RNAs. Here we describe how to extract RNA from mycobacterial cultures, how to
      prepare libraries for Illumina sequencing, and the bioinformatics analysis of the
      sequencing data to determine the transcription profile. 

PMID- 25779309
TI  - RNA sequencing for transcript 5'-end mapping in mycobacteria.
AB  - Next-generation sequencing technologies facilitate the analysis of multiple
      important properties of the transcriptome in addition to gene expression levels.
      Here we describe a method for mapping RNA 5' ends in Mycobacterium tuberculosis,
      which allows the determination of transcriptional start sites (TSSs), comparative
      analysis of promoter usage under different conditions, and mapping of
      endoribonucleolytic processing sites. We describe in detail the procedures for
      constructing RNA sequencing libraries appropriate for RNA 5' end mapping using an
      Illumina sequencing platform. We also outline the major steps of data analysis. 

PMID- 25779310
TI  - Fractionation and analysis of mycobacterial proteins.
AB  - The extraction and isolation of native bacterial proteins continue to be valuable
      technical pursuits in order to understand bacterial physiology, screen for
      virulence determinants, and describe antigens. In this chapter, methods for the
      manipulation of whole mycobacterial cells are described in detail. Specifically,
      the concentration of spent culture filtrate media is described in order to permit
      separation of soluble, secreted proteins; several discrete separation techniques,
      including precipitation of protein mixtures with ammonium sulfate and separation
      of proteins by hydrophobic chromatography are also provided. Similarly, the
      generation of whole cell lysate and facile separation of lysate into subcellular
      fractions to afford cell wall, cell membrane, and cytosol enriched proteins is
      described. Due to the hydrophobic nature of cell wall and cell membrane proteins,
      several extraction protocols to resolve protein subsets (such as extraction with
      urea and SDS) are also provided, as well as a separation technique (isoelectric
      focusing) that can be applied to separate hydrophobic proteins. Lastly, two
      commonly used analytical techniques, in-gel digestion of proteins for LC-MS and
      analysis of intact proteins by MALDI-ToF MS, are provided for rapid analysis of
      discrete proteins within subcellular or chromatographic fractions. While these
      methods were optimized for the manipulation of Mycobacterium tuberculosis cells,
      they have been successfully applied to extract and isolate Mycobacterium leprae,
      Mycobacterium ulcerans, and Mycobacterium avium proteins. In addition, a number
      of these methods may be applied to extract and analyze mycobacterial proteins
      from cell lines and host derived samples. 

PMID- 25779311
TI  - Lipid and lipoarabinomannan isolation and characterization.
AB  - Mycobacteria are microorganisms that contain a very high content of structurally
      diverse lipids, some of them being biologically active substances. As such the
      lipid composition is commonly used to characterize mycobacterial strains at the
      species and type-species level. This chapter describes the methods that allow the
      purification of the most commonly isolated biologically active lipids and those
      used for analyzing extractable lipids and their constituents, cell wall-linked
      mycolic acids and lipoarabinomannan (LAM). The latter involve simple
      chromatographic and analytical techniques, such as thin-layer chromatography and
      gas chromatography coupled to mass spectrometry. 

PMID- 25779312
TI  - Metabolomics of Mycobacterium tuberculosis.
AB  - Enzymes fuel the biochemical activities of all cells. Their substrates and
      products thus offer a potential window into the physiologic state of a cell.
      Metabolomics focuses on the global, or systems-level, study of small molecules in
      a given biological system and thus provided an experimental tool with which to
      study cellular physiology on a global biochemical scale. While metabolomic
      studies of Mycobacterium tuberculosis are still in their infancy, recent studies
      have begun to deliver unique insights into the composition, organization,
      activity, and regulation of M. tuberculosis' physiologic network. Here, we
      outline practical methods for the culture, collection, and analysis of
      metabolomic samples from Mycobacterium tuberculosis that emphasize minimal sample
      perturbation, broad and native metabolite recovery, and sensitive, biologically
      agnostic metabolite detection. 

PMID- 25779313
TI  - Electroporation of mycobacteria.
AB  - High-efficiency transformation of DNA is integral to the study of mycobacteria,
      allowing genetic manipulation. Electroporation is the most widely used method for
      introducing DNA into mycobacterial strains. Many parameters contribute to high
      efficiency transformation; these include the species per strain, the transforming
      DNA, the selectable marker, the growth medium additives, and the conditions of
      electroporation. In this chapter we provide an optimized method for the
      transformation of representative slow- and fast-growing species of mycobacteria
      Mycobacterium tuberculosis and M. smegmatis, respectively. 

PMID- 25779314
TI  - Targeted gene knockout and essentiality testing by homologous recombination.
AB  - This chapter provides an updated experimental protocol for generating allelic
      exchange mutants of mycobacteria by two-step selection using the p2NIL/pGOAL
      system. The types of mutants that can be generated using this approach are
      targeted gene knockouts marked with a drug resistance gene, unmarked deletion
      mutants, or strains in which a point mutation/s has been introduced into the
      target gene. A method for assessing the essentiality of a gene for mycobacterial
      growth by means of allelic exchange is also described. This method, which
      utilizes a merodiploid strain carrying a second copy of the gene of interest on
      an integration vector, allows the exploration by means of complement switching of
      structure-function relationships in proteins that are essential for mycobacterial
      growth. 

PMID- 25779315
TI  - Construction of conditional knockdown mutants in mycobacteria.
AB  - By definition, essential genes are fundamental to bacterial growth, yet the
      functions of many such genes remain unknown. Essential genes furthermore are
      central to the activity of most antibacterial drugs and among the most attractive
      targets for the development of new therapeutics. This chapter describes how
      synthetic genetic switches that utilize transcriptional repression, controlled
      proteolysis, or both to silence gene activity can be applied to construct and
      characterize conditional knockdown (cKD) mutants for essential genes in
      Mycobacterium smegmatis and Mycobacterium tuberculosis. 

PMID- 25779316
TI  - Mycobacterial recombineering.
AB  - The precise knockout or modification of Mycobacterium tuberculosis genes has been
      critical for the identification of functions important for the growth and
      pathogenicity of this important bacterium. Schemes have been previously
      described, using both non-replicating vectors and transducing particles, for the
      introduction of gene knockout substrates into M. tuberculosis, where the
      endogenous recombination systems of the host (both homologous and illegitimate)
      compete for transfer of the modified allele to the chromosome. Recombineering
      technologies, first introduced in laboratory and pathogenic strains of
      Escherichia coli over the last 16 years, have been developed for use in M.
      tuberculosis. Described in this chapter is the use of the mycobacterial Che9c
      phage RecET recombination system, which has been used to make gene knockouts,
      reporter fusions, promoter replacements, and single base pair modifications
      within the M. tuberculosis and M. smegmatis chromosomes at very high frequency.
      Higher success rates, in a shorter period of time, are routinely observed when
      recombineering is compared to previously described M. tuberculosis gene knockout
      protocols. 

PMID- 25779317
TI  - In vitro models that utilize hypoxia to induce non-replicating persistence in
      Mycobacteria.
AB  - The Wayne model and Rapid Anaerobic Dormancy model are widely used methods to
      analyze the response of Mycobacterium tuberculosis to hypoxia and anaerobiosis.
      In these models tubercle bacilli are grown in sealed tubes in which bacilli
      aerobic respiration produces a temporal oxygen gradient. The gradual depletion of
      oxygen results in a non-replicating persistent culture capable of extended
      microaerobic and anaerobic survival. Here we describe both models used to induce
      hypoxic non-replicating persistence in M. tuberculosis. Additional techniques
      such as the isolation of RNA, the detection of nitrate reductase activity and ATP
      levels, and the determination of the NAD(+)/NADH ratio are described. 

PMID- 25779318
TI  - Genetic dissection of mycobacterial biofilms.
AB  - Our understanding of the biological principles of mycobacterial tolerance to
      antibiotics is crucial for developing shorter anti-tuberculosis regimens. Various
      in vitro approaches have been developed to identify the conditions that promote
      mycobacterial persistence against antibiotics. In our laboratories, we have
      developed a detergent-free in vitro growth model, in which mycobacteria
      spontaneously grow at the air-medium interface as self-organized multicellular
      structures, called biofilms. Mycobacterial biofilms harbor a subpopulation of
      drug tolerant persisters at a greater frequency than their planktonic
      counterpart. Importantly, development of these structures is genetically
      programmed, and defective biofilms of isogenic mutants harbor fewer persisters.
      Thus, genetic analysis of mycobacterial biofilms in vitro could potentially be a
      powerful tool to unravel the biology of drug tolerance in mycobacteria. In this
      chapter we describe a method for screening biofilm-defective mutants of
      mycobacteria in a 96-well format, which readily yields a clonally pure mutant for
      further studies. 

PMID- 25779319
TI  - Measuring efflux and permeability in mycobacteria.
AB  - The intrinsic resistance of mycobacteria to most antimicrobial agents is mainly
      attributed to the synergy between their relatively impermeable cell wall and
      efflux systems. The mycobacterial cell wall is rich in lipids and polysaccharides
      making a compact envelope that limits drug uptake. Changes in cell wall
      composition or structure lead to variations in susceptibility to drugs. Bacterial
      efflux pumps are membrane proteins that are capable of actively transporting a
      broad range of substrates, including drugs, from the cytoplasm to the
      extracellular environment. Increased expression of efflux pump genes confers a
      low level resistance phenotype, and under these conditions, bacteria may have
      greater chances of acquiring chromosomal mutation(s) conferring higher levels of
      drug resistance. In order to develop effective antimycobacterial therapeutic
      strategies, the contributions to drug resistance made by the limited permeability
      of the cell wall and the increased expression of efflux pumps must be understood.
      In this chapter, we describe a method that allows: (1) the quantification of
      general efflux activity of mycobacterial strains (clinical isolates, mutants
      impaired in efflux or permeability) by the study of the transport (influx and
      efflux) of fluorescent compounds, such as ethidium bromide; and (2) the screening
      of compounds in search of inhibitors of efflux pumps, which could restore the
      effectiveness of antimicrobials that are subject to efflux. 

PMID- 25779320
TI  - Single-cell analysis of mycobacteria using microfluidics and time-lapse
      microscopy.
AB  - The crucial role of phenotypic heterogeneity in bacterial physiology and adaptive
      responses has required the introduction of new ways to investigate bacterial
      individuality. Time-lapse microscopy is a powerful technique for evaluating
      phenotypic diversity in bacteria at the single-cell level, whether exploring the
      dynamics of gene expression and protein localization or characterizing the
      heterogeneous phenotypic response to perturbations. Here, we present protocols to
      carry out time-lapse imaging of mycobacteria at the single-cell level using
      either agarose pads or customized microfluidic devices. The sequences of images
      obtained can be analyzed using programs such as ImageJ and allow the investigator
      not only to extract various parameters of growth and gene expression dynamics but
      also to unravel the physiological basis behind phenomenon such as persistence
      against stresses. 

PMID- 25779321
TI  - Antimicrobial susceptibility testing for Mycobacterium sp.
AB  - The concept of antimicrobial susceptibility testing is an essential part of
      clinical microbiology. Antimicrobial testing has played a central role in the
      identification of new antibiotics and defining their clinical uses. Here we
      describe different approaches to determine the activity of compounds in medium-
      or high-throughput format. 

PMID- 25779322
TI  - Determination of compound kill kinetics against Mycobacterium tuberculosis.
AB  - In this chapter, we describe how to determine the kill kinetics and minimum
      bactericidal concentration (MBC) of a compound against Mycobacterium
      tuberculosis. Techniques are described for three conditions: actively growing
      aerobic bacteria, and non-replicating bacteria induced by nutrient starvation
      and/or low pH. Each technique involves determining the number of viable bacteria
      in the presence of several concentrations of compound over 3 weeks. Guidelines
      for how to interpret the results, to determine if growth-inhibitory compounds are
      bactericidal or bacteriostatic and also whether compounds exhibit time-dependent
      or concentration-dependent kill are provided. 

PMID- 25779323
TI  - Microplate Alamar Blue Assay (MABA) and Low Oxygen Recovery Assay (LORA) for
      Mycobacterium tuberculosis.
AB  - Throughput in tuberculosis drug discovery was extremely limited prior to the
      introduction of microplate-based susceptibility assays. The 96-well Microplate
      Alamar Blue Assay (MABA) allows for the quantitative determination of drug
      susceptibility against any strain of replicating Mycobacterium tuberculosis to be
      completed within a week at minimal cost. The Low-Oxygen Recovery Assay (LORA)
      uses a recombinant M. tuberculosis expressing luciferase and provides results of
      drug activity against non-replicating M. tuberculosis surviving under hypoxic
      conditions. Determining activity against non-replicating M. tuberculosis is an
      important factor when developing drug candidates against M. tuberculosis. Here we
      describe a step-by-step procedure for both the MABA and LORA. 

PMID- 25779324
TI  - A multi-stress model for high throughput screening against non-replicating
      Mycobacterium tuberculosis.
AB  - Models of non-replication help us understand the biology of persistent
      Mycobacterium tuberculosis. High throughput screening (HTS) against non
      replicating M. tuberculosis may lead to identification of tool compounds that
      affect pathways on which bacterial survival depends in such states, and to
      development of drugs that can overcome phenotypic tolerance to conventional
      antimycobacterial agents, which are mostly active against replicating M.
      tuberculosis. We describe a multi-stress model of non-replication that mimics
      some of the microenvironmental conditions that M. tuberculosis faces in the host
      as adapted for HTS. The model includes acidic pH, mild hypoxia, a flux of nitric
      oxide and other reactive nitrogen intermediates arising from nitrite at low pH,
      and low concentrations of a fatty acid (butyrate) as a carbon source. 

PMID- 25779325
TI  - Isolation and characterization of compound-resistant isolates of Mycobacterium
      tuberculosis.
AB  - This chapter describes the isolation and characterization of spontaneous
      resistant mutants of Mycobacterium tuberculosis. The overall objective of
      resistant mutant isolation is to determine the mode of action and/or cellular
      targets of new antimycobacterial agents. Whole-genome sequencing of resistant
      mutants can identify targets of antimycobacterial drugs and mechanisms of
      resistance, such as efflux, changes in drug permeability, or drug recognition.
      Mutants allow insight into in vivo biological processes and can help elucidate
      the number and identity of genes in a given pathway. Resistant mutant
      characterization can also lay the groundwork for structure/function studies,
      especially in conjunction with binding studies and X-ray crystallography. 

PMID- 25779326
TI  - Macrophage infection models for Mycobacterium tuberculosis.
AB  - Mycobacterium tuberculosis colonizes, survives, and grows inside macrophages. In
      vitro macrophage infection models, using both primary macrophages and cell lines,
      enable the characterization of the pathogen response to macrophage immune
      pressure and intracellular environmental cues. We describe methods to propagate
      and infect primary murine bone marrow-derived macrophages and J774 and THP-1
      macrophage-like cell lines. We also present methods on the characterization of M.
      tuberculosis intracellular survival and the preparation of infected macrophages
      for imaging. 

PMID- 25779327
TI  - Infection of human neutrophils to study virulence properties of Mycobacterium
      tuberculosis.
AB  - Polymorphonuclear neutrophils (PMN) are professional phagocytes and the first
      line of defense against invading microbes. Upon infection with Mycobacterium
      tuberculosis, PMN are attracted to the site of infection along an interleukin 8
      gradient. In patients with active tuberculosis, PMN comprise the predominant
      population in the lung and carry the main mycobacterial load suggesting a minor
      role for PMN in protective host defense against M. tuberculosis but rather in
      pathology. Therefore, better understanding of PMN biology in tuberculosis is of
      pivotal importance to develop novel immune modulating measures and host directed
      therapies. Virulent M. tuberculosis escape the otherwise microbicidal
      armamentarium of PMNs by inducing necrotic cell death through the PMN's own
      reactive oxygen species. Studying the interactions between PMN and different M.
      tuberculosis strains, and virulence factors thereof, is vital to comprehend
      tuberculosis pathogenesis. Working with PMN is challenging as these cells are non
      adherent, motile and-with a half-life of 6-12 h in vitro-rather short-lived.
      Here, we provide an isolation and infection protocol that is tailored to study
      mycobacterial infection in human PMN regarding the intracellular fate of
      mycobacteria and host cell responses, such as cell death and release of
      microbicidal effectors. 

PMID- 25779328
TI  - Isolation of bead phagosomes to study virulence function of M. tuberculosis cell
      wall lipids.
AB  - Following pathogen recognition by macrophages, the causative agent of human
      tuberculosis, Mycobacterium tuberculosis, is internalized by receptor-mediated
      phagocytosis. Phagosomes containing nonpathogenic bacteria usually follow a
      stepwise maturation process to phagolysosomes where bacteria are eliminated.
      However, as a hallmark of M. tuberculosis virulence, pathogenic mycobacteria
      inhibit phagosome maturation in order to generate an intracellular niche for
      persistence and replication in resting macrophages. In contrast, activation by
      interferon gamma and tumor necrosis alpha activates microbicidal effectors of
      macrophages such as nitric oxide synthase, NO-mediated apoptosis and LRG-47
      linked autophagy, which drives M. tuberculosis into phagolysosomes. Glycolipid
      compounds of the mycobacterial cell wall have been suggested as virulence factors
      and several studies revealed their contribution to mycobacterial interference
      with phagosome maturation. To study their effect on phagosome maturation and to
      characterize phagosomal protein and lipid compositions, we developed a
      reductionist mycobacterial lipid-coated bead model. Here, we provide protocols to
      "infect" macrophages with lipid-coated magnetic beads for subsequent purification
      and characterization of bead phagosomes. This model has been successfully
      employed to characterize the virulence properties of trehalose dimycolate, as one
      of the cell wall glycolipids essential for inhibition of phagosome maturation. 

PMID- 25779329
TI  - Live imaging of Mycobacterium marinum infection in Dictyostelium discoideum.
AB  - The Dictyostelium discoideum-Mycobacterium marinum host-pathogen system is a
      recently established and powerful model system for mycobacterial infection. In
      this chapter, two simple protocols for live imaging of Dictyostelium discoideum
      infection are described. The first method is used to monitor the dynamics of
      recruitment of GFP-tagged Dictyostelium discoideum proteins at single time-points
      corresponding to the main stages of the infection (1.5-72 h post infection). The
      second method focuses at the early stages of the establishment of an infection (0
      3 h post infection). In addition, several procedures to improve the imaging of
      the bacterium-containing compartment are described. Basic bacterial parameters
      such as bacterial growth and the recruitment of host proteins to the bacterium
      containing compartment can be easily and precisely quantified using macros for
      ImageJ. These methods can be adapted to monitoring mycobacteria infection in
      other systems using mammalian cells. 

PMID- 25779330
TI  - Testing chemical and genetic Modulators in Mycobacterium tuberculosis infected
      cells using phenotypic assays.
AB  - Mycobacterium tuberculosis is able to colonize host cells, and it is now well
      admitted that the intracellular stage of the bacteria contributes to tuberculosis
      pathogenesis as well as to making it a persistent infection. There is still
      limited understanding on how the tubercle bacillus colonizes the cell and what
      are the factors impacting on its intracellular persistence. Recent advances in
      imaging technique allow rapid quantification of biological objects in complex
      environments. Furthermore, M. tuberculosis is a microorganism that is
      particularly genetically tractable and that tolerates the expression of
      heterologous fluorescent proteins. Thus, the intracellular distribution of M.
      tuberculosis expressing fluorescent proteins can be easily quantified by the use
      of confocal microscopy. Here we describe high-content/high-throughput imaging
      methods that enable tracking the bacillus inside host settings, taking into
      account the heterogeneity of colonization. 

PMID- 25779331
TI  - CCR2 Expression in Neutrophils Plays a Critical Role in Their Migration Into the
      Joints in Rheumatoid Arthritis.
AB  - OBJECTIVE: Infiltration of neutrophils into the joints plays an important role in
      bone erosion and articular destruction in rheumatoid arthritis (RA). Neutrophil
      trafficking during inflammation is a process that involves activation of
      chemotactic receptors. Recent findings suggest that changes in chemotactic
      receptor patterns could occur in neutrophils under certain inflammatory
      conditions. The aim of this study was to evaluate the gain of responsiveness of
      neutrophils to CCL2 in RA patients and to assess the role of CCL2 in driving
      neutrophil infiltration into the joints. METHODS: Neutrophils were purified from
      the peripheral blood of patients with RA or from mice with antigen-induced
      arthritis (AIA). Expression of CCR2 was evaluated using polymerase chain
      reaction, flow cytometry, and immunofluorescence analyses. In vitro chemotaxis to
      CCL2 was assayed to evaluate the functional significance of de novo CCR2
      expression. The murine AIA model was used to evaluate the in vivo role of CCR2 in
      neutrophil infiltration into the joints. RESULTS: High CCR2 expression and
      responsiveness to CCL2 were observed in neutrophils from the blood of patients
      with early RA and in neutrophils from the blood and bone marrow of mice with AIA.
      Genetic deficiency or pharmacologic inhibition of CCR2 protected against the
      infiltration of neutrophils into the joints. This protection was not associated
      with an impairment of the neutrophil chemotactic ability or CXC chemokine
      production in the joints. Moreover, adoptive transfer of wild-type mouse
      neutrophils to CCR2-deficient mice restored neutrophil infiltration and the
      articular mechanical hyperalgesia associated with joint inflammation. CONCLUSION:
      These findings suggest that CCR2 is directly involved in the detrimental
      infiltration of neutrophils into the joints in patients with RA, showing a new
      inflammatory role of CCR2 during RA flares or active disease.

PMID- 25779332
TI  - Twelve key nutritional issues in bariatric surgery.
AB  - In morbidly obese patients, i.e. body mass index >=35, bariatric surgery is
      considered the only effective durable weight-loss therapy. Laparoscopic Roux-en-Y
      gastric bypass (LRYGBP), laparoscopic sleeve gastrectomy (LSG), and
      biliopancreatic diversion with duodenal switch (BPD-DS) are associated with risks
      of nutritional deficiencies and malnutrition. Therefore, preoperative nutritional
      assessment and correction of vitamin and micronutrient deficiencies, as well as
      long-term postoperative nutritional follow-up, are advised. Dietetic counseling
      is mandatory during the first year, optional later. Planned and structured
      physical exercise should be systematically promoted to maintain muscle mass and
      bone health. In this review, twelve key perioperative nutritional issues are
      raised with focus on LRYGBP and LSG procedures, the most common current bariatric
      procedures. 

PMID- 25779333
TI  - Metallothioneins and heat shock proteins 70 in Armadillidium vulgare (Isopoda,
      Oniscidea) exposed to cadmium and lead.
AB  - The heavy metals bioaccumulation capability in Armadillidium vulgare feeded with
      chestnut leaves contaminated with various sublethal concentrations of Cd and Pb,
      was evaluated under laboratory conditions. The metal concentration found in the
      hepatopancreas of treated animals, as measured by Inductively Coupled Plasma Mass
      Spectrometry (ICP-MS), affected the expression and localization of MT and HSP70
      as shown by immunohistochemical and western blotting analysis. The Cd content of
      the animals treated with the various concentrations of the metal has been always
      higher than that of chestnut leaves contaminated. The accumulation of Pb was,
      instead, always modest compared to the content of the chestnut leaves. The
      immunohistochemical investigation in hepatopancreas tissue of animals treated
      with increasing concentrations of Cd and Pb, by using the anti-MT and anti-HSP70
      antibodies, has provided a response clearly positive even if differentiated in
      relation to the metal and concentration tested. In particular, a positive
      response to anti-MT antibody was detected in B and S cells nuclei and S cells
      cytoplasm; the localization of HSP70 was particularly intense at the cell
      surface. Western blotting analysis showed significant up-regulation of the
      expression (about 2.6 fold) of HSP70 proteins in the hepatopancreas of animals
      exposed to highest Pb concentrations respect to control. Moreover, samples
      exposed to higher Cd and Pb concentrations showed a higher expression of MT (3.2
      fold and 4 fold respectively) compared to control. In summary, our data beyond to
      clearly demonstrate for the first time the expression of MT in terrestrial
      isopods, suggest that A. vulgare would be a suitable organism for assessing Cd
      and Pb exposure in environments threatened by metal pollution as suggested by the
      modulation of the biomarkers MT and HSP70. 

PMID- 25779334
TI  - Rethinking cellular targets for lead neurotoxicity.

PMID- 25779335
TI  - Glyphosate resistance in Echinochloa colona: phenotypic characterisation and
      quantification of selection intensity.
AB  - BACKGROUND: A population of Echinochloa colona infesting agricultural fields in
      the northern region of Western Australia evolved glyphosate resistance after 10
      years of glyphosate selection. This study identified two phenotypic (susceptible
      S versus resistant R) lines from within a segregating glyphosate-resistant
      population. Estimation of survival, growth and reproductive rates of the
      phenotypes in response to glyphosate selection helped to characterise the level
      of resistance, fitness and the selection intensity for glyphosate in this
      species. RESULTS: Estimations of LD(50) (lethal dose) and GR(50) (growth rate)
      showed an eightfold glyphosate resistance in this population. The resistant index
      based on the estimation of seed number (SY(n50)) showed a 13-fold resistance. As
      a result of linear combination of plant survival and fecundity rates, plant
      fitness values of 0.2 and 0.8 were estimated for the S and R phenotypes when
      exposed to the low dose of 270 g glyphosate ha(-1). At the recommended dose of
      540 g glyphosate ha(-1) , fitness significantly decreased (fivefold) in S plants
      but remained markedly similar (0.7) in plants of the R phenotype. Thus, the
      calculated selection intensity (SI) at 540 g glyphosate ha(-1) was much greater
      (SI = 17) than at 270 g glyphosate ha(-1) (SI = 4). CONCLUSIONS: The assessment
      of plant survival and fecundity in response to glyphosate selection in the S and
      R phenotypes allowed a greater accuracy in the estimation of population fitness
      of both phenotypes and thus of glyphosate selection intensity in E. colona. The
      estimation of seed number or mass of phenotypes under herbicide selection is a
      true ecological measure of resistance with implications for herbicide resistance
      evolution.

PMID- 25779336
TI  - Extracellular vesicles secreted by bone marrow- and adipose tissue-derived
      mesenchymal stromal cells fail to suppress lymphocyte proliferation.
AB  - Recently, mesenchymal stromal cell-derived extracellular vesicles (MSC-EVs) have
      been suggested as an alternative to MSCs for the treatment of various
      inflammatory disorders. However, while a first case report observed beneficial
      therapeutic effects of repeated MSC-EV infusions in a patient with therapy
      refractory graft-versus-host disease, in vitro findings revealed that MSC-EVs
      were significantly less immunosuppressive than their parental cells. In this
      study, we compared the immunosuppressive potency of MSCs derived from bone marrow
      (BM-MSCs) and adipose tissue (AT-MSCs), with their secreted EVs in a standardized
      lymphocyte proliferation assay (LPA). Both BM-MSCs and AT-MSCs exhibited a
      remarkable inhibition of lymphocyte proliferation (LP) (88.1%+/-1.5% and 75.5%+/
      1.5%, respectively), while isolated EVs derived from them failed to suppress LP
      at dose levels up to 100 MUg/mL. Thus, our data further substantiate previous
      reports suggesting that cell-cell contact plays an important role on the
      immunosuppressive potential mediated by MSCs. Hence, MSC-EVs are still a matter
      of debate and might not be a reasonable substitute for MSCs with regard to the
      immunosuppressive function. Collectively, these contrasting findings may also
      reflect the importance of relevant translational aspects when designing new
      studies. Standardization of MSC culture conditions before EV collection as well
      as isolation and characterization methods with regard to EV purity are urged.
      Moreover, before clinical use, dose-finding studies evaluating MSC-EV
      preparations in suitable preclinical models are warranted. 

PMID- 25779337
TI  - Is solid-state NMR enhanced by dynamic nuclear polarization?
AB  - The recent trend of high-field (~5-20 T), low-temperature (~100 K) ssNMR combined
      with dynamic nuclear polarization (DNP) under magic angle spinning (MAS)
      conditions is analyzed. A brief overview of the current theory of
      hyperpolarization for so-called MAS-DNP experiments is given, along with various
      reasons why the DNP-enhancement, the ratio of the NMR signal intensities obtained
      in the presence and absence of microwave irradiation suitable for
      hyperpolarization, should not be used alone to gauge the value of performing MAS
      DNP experiments relative to conventional ssNMR. This is demonstrated through a
      dissection of the current conditions required for MAS-DNP with particular
      attention to resulting absolute sensitivities and spectral resolution.
      Consequently, sample preparation methods specifically avoiding the surplus of
      glass-forming solvents so as to improve the absolute sensitivity and resolution
      are discussed, as are samples that are intrinsically pertinent for MAS-DNP
      studies (high surface area, amorphous, and porous). Owing to their pertinence,
      examples of recent applications on these types of samples where chemically
      relevant information has been obtained that would have been impossible without
      the sensitivity increases bestowed by MAS-DNP are also detailed. Additionally, a
      promising further implementation for MAS-DNP is exampled, whereby the sensitivity
      improvements shown for (correlation) spectroscopy of nuclei at low natural
      isotopic abundance, facilitate internuclear distance measurements, especially for
      long distances (absence of dipolar truncation). Finally, we give some speculative
      perspectives for MAS-DNP.

PMID- 25779338
TI  - Regulation of adipogenesis and osteogenesis in mesenchymal stem cells by vascular
      endothelial growth factor A.
AB  - Understanding the mechanisms by which bone marrow mesenchymal stem cells (BMSCs)
      differentiate into bone-forming osteoblasts and marrow adipocytes is crucial to
      develop strategies for the treatment of several bone diseases. Age-related bone
      loss resulting in osteopenia and osteoporosis has been associated with reduced
      numbers of osteoblasts and increased numbers of adipocytes, likely originating
      from differentiation defects in BMSCs. Although many factors involved in the
      complex regulation of osteoblast and adipocyte cell lineages have previously been
      identified, their functional interactions in the context of BMSC differentiation
      and maintenance of bone homeostasis during ageing are unknown. Recent discoveries
      have provided important new insights into the mechanisms by which the nuclear
      envelope protein lamin A and vascular endothelial growth factor A (VEGF) mutually
      control BMSC fate. Particularly interesting is the finding that VEGF in this
      context functions as an intracellular protein, unaffected by neutralizing
      antibodies, and not as a secreted growth factor. These insights may not only
      facilitate the identification of new targets for treating bone diseases but also
      lead to improved design of tissue engineering approaches aimed at stimulating
      bone regeneration and repair. 

PMID- 25779339
TI  - Identification and structural composition of the blood-spleen barrier in
      chickens.
AB  - To identify the existence and composition of the blood-spleen barrier (BSB) in
      chickens, the microanatomical features of the spleen were investigated by light
      and transmission electron microscopy, intravenous injection of ink, acid
      phosphatase reaction, and silver impregnation. The results showed that the white
      pulp in chicken spleen consists of lymphoid nodules, periarteriolar lymphatic
      sheaths (PALS) and periellipsoidal lymphatic sheaths (PELS). There was no
      evidence for the presence of a marginal zone. The splenic ellipsoid was a unique
      structure, which functioned as a barrier for filtering and phagocytosis. Uptake
      of carbon particles was limited to the ellipsoid and PELS, 60 min after injection
      of carbon particles. Reticular fibres were densely distributed in the ellipsoid
      and extended into the PELS. Ellipsoid-associated cells (EACs), reticular cells
      and macrophages were acid phosphatase positive. The sheathed capillaries,
      surrounded by the ellipsoid, were similar to high endothelial venules (HEVs).
      These findings suggest that the BSB of chickens is present in the ellipsoid and
      PELS, protecting the spleen from invasion from circulating pathogens. The BSB was
      a reticular framework, between the arterial and venous vessels, which included
      cuboidal-shaped endothelial cells, supporting cells, EACs, macrophages, reticular
      cells and fibres. Lymphocyte migration into the spleen parenchyma is most likely
      via the HEV-like vessels. These research findings contribute to better
      understanding of avian immunology and provide an insight into evolutionary
      differences in the immune system.

PMID- 25779340
TI  - Human BDCA2+CD123+CD56+ dendritic cells (DCs) related to blastic plasmacytoid
      dendritic cell neoplasm represent a unique myeloid DC subset.
AB  - Dendritic cells (DCs) comprise two functionally distinct subsets: plasmacytoid
      DCs (pDCs) and myeloid DCs (mDCs). pDCs are specialized in rapid and massive
      secretion of type I interferon (IFN-I) in response to nucleic acids through Toll
      like receptor (TLR)-7 or TLR-9. In this report, we characterized a CD56(+) DC
      population that express typical pDC markers including CD123 and BDCA2 but produce
      much less IFN-I comparing with pDCs. In addition, CD56(+) DCs cluster together
      with mDCs but not pDCs by genome-wide transcriptional profiling. Accordingly,
      CD56(+) DCs functionally resemble mDCs by producing IL-12 upon TLR4 stimulation
      and priming naive T cells without prior activation. These data suggest that the
      CD56(+) DCs represent a novel mDC subset mixed with some pDC features. A
      CD4(+)CD56(+) hematological malignancy was classified as blastic plasmacytoid
      dendritic cell neoplasm (BPDCN) due to its expression of characteristic molecules
      of pDCs. However, we demonstrated that BPDCN is closer to CD56(+) DCs than pDCs
      by global gene-expression profiling. Thus, we propose that the CD4(+)CD56(+)
      neoplasm may be a tumor counterpart of CD56(+) mDCs but not pDCs. 

PMID- 25779341
TI  - Current aging research in China.
AB  - The mini-review stemmed from a recent meeting on national aging research
      strategies in China discusses the components and challenges of aging research in
      China. Highlighted are the major efforts of a number of research teams, funding
      situations and outstanding examples of recent major research achievements.
      Finally, authors discuss potential targets and strategies of aging research in
      China. 

PMID- 25779342
TI  - Chemoprotective effect of vitamin E in cyclophosphamide-induced hepatotoxicity in
      rats.
AB  - Cyclophosphamide (CP) has a range of adverse effects on liver tissue in humans
      and animals. Administering an antioxidant with CP might reduce such side effects.
      Therefore, we examined the role of vitamin E in CP-induced liver toxicity in
      rats. Male Wistar albino rats were divided into four groups, each of seven rats:
      control, CP only, CP + vitamin E, and vitamin E only groups. The rats were
      administered treatments intraperitoneally for 7 days. Then the serum
      malondialdehyde (MDA), alanine aminotransferase (ALT), aspartate transaminase
      (AST), and lactate dehydrogenase (LDH) levels were determined while the livers
      were removed, tissue was prepared using routine histological procedures, sections
      were stained using hematoxylin and eosin, and the terminal deoxynucleotidyl
      transferase-mediated nick end-labeling (TUNEL) method was applied.
      Histopathologically, CP caused hydropic degeneration, necrosis, pleomorphism, and
      mitotic activity. The number of TUNEL-positive cells and the MDA and ALT levels
      were significantly higher in the CP group. The antioxidant effects of vitamin E
      significantly decreased the number of TUNEL-positive cells and the ALT and MDA
      levels, and normalized the liver histopathology. CP induces apoptosis, has toxic
      effects on liver tissue, and changes the histological structure. The
      administration of vitamin E prevented the liver tissue damage caused by CP.

PMID- 25779343
TI  - Regulation of hepatic carbohydrate metabolism by Selenium during diabetes.
AB  - In the present study, we have tried to unravel the role of Selenium
      supplementation in containing hyperglycemia by regulating enzymes activities
      involved in carbohydrate metabolism in liver of diabetic animals. Male wistar
      rats were divided into four groups: normal control, diabetic, Selenium treated
      control and Selenium treated diabetic group. Diabetes was induced in the animals
      by injecting alloxan intraperitoneally at a dose level of 150 mg/kg body weight.
      Selenium in the form of sodium selenite was supplemented to rats at a dose level
      of 1 PPM in drinking water, ad libitum for two time durations of 2 and 4 weeks.
      Animals were sacrificed and livers were excised for the analyses of enzymes
      involved in carbohydrate metabolism as well as the levels of glycogen. In-vitro
      (14)C-d glucose uptake and its turnover were also assessed in liver slices of all
      the treatment groups using radiorespirometry. Selenium supplementation to the
      diabetic rats normalized the enzyme activities of glucose-6-phosphatase, lactate
      dehydrogenase and glycogen phosphorylase as well as restored the glycogen levels
      to within the normal limits which were altered during diabetes. Interestingly,
      when Selenium was supplemented to diabetic rats, (14)C-d glucose uptake and its
      turnover showed a statistically significant increase in their values which
      however, were decreased in diabetic rats. In conclusion, Selenium mediates
      insulin-like role during diabetes by tending to normalize the altered activities
      of glucose metabolizing enzymes and also improves the glucose uptake and its
      metabolism by the liver.

PMID- 25779344
TI  - Incidental lung volume reduction following fulminant pulmonary hemorrhage in a
      patient with severe emphysema.
AB  - Endoscopic lung volume reduction is an emerging technique meant to improve lung
      function parameters, quality of life, and exercise tolerance in patients with
      severe lung emphysema. This is the first report of lung volume reduction by
      autologous blood in a patient with non-bullous lung emphysema. A 74-year-old
      woman with heterogeneous lung emphysema developed accidentally diffuse lobar
      bleeding immediately after valve placement. Due to persistent hemorrhage, the
      valves had to be removed shortly thereafter. Despite extraction of the valves,
      respiratory function of the patient improved rapidly indicated also by a drop in
      the COPD assessment test questionnaire, 3 months later. This was consistent with
      both improvement of lung function tests and six-minute walking test.

PMID- 25779345
TI  - Thickness-dependent mobility in two-dimensional MoS2 transistors.
AB  - Two-dimensional (2D) semiconductors such as mono and few-layer molybdenum
      disulphide (MoS2) are very promising for integration in future electronics as
      they represent the ultimate miniaturization limit in the vertical direction.
      While monolayer MoS2 attracted considerable attention due to its broken inversion
      symmetry, spin/valley coupling and the presence of a direct band gap, few-layer
      MoS2 remains a viable option for technological application where its higher
      mobility and lower contact resistance are believed to offer an advantage.
      However, it remains unclear whether multilayers are intrinsically superior or if
      they are less affected by environmental effects. Here, we report the first
      systematic comparison of the field-effect mobilities in mono-, bi- and trilayer
      MoS2 transistors after thorough in situ annealing in vacuum. We show that the
      mobility of field-effect transistors (FETs) based on monolayer MoS2 is
      significantly higher than that of FETs based on two or three layers. We
      demonstrate that it is important to remove the influence of gaseous adsorbates
      and water before comparing mobilities, as monolayers exhibit the highest
      sensitivity to ambient air exposure. In addition, we study the influence of the
      substrate roughness and show that this parameter does not affect FET mobilities. 

PMID- 25779346
TI  - Trends and variations in the epidemiology of meningococcal disease in Kuwait 1987
      2013.
AB  - The introduction of Haemophilus influenzae type b (Hib) conjugate vaccine and
      conjugate pneumococcal vaccine into routine childhood vaccination in Kuwait has
      resulted in the emergence of Neisseria meningitidis as the leading cause of
      invasive bacterial infection in children. Currently, a quadrivalent ACYW-135
      meningococcal polysaccharide vaccine is administered as part of routine childhood
      vaccination in Kuwait at the age of 2 years. Conjugate meningococcal vaccines
      have been shown to be more effective in preventing meningococcal infection in
      young children. The objective of this study was to describe the epidemiology of
      meningococcal disease (MD) in Kuwait and evaluate the need for conjugate vaccine
      in routine childhood immunization. We have reviewed the MD surveillance data from
      the communicable disease unit, Ministry of Health, Kuwait during the period from
      1987 to 2013. The analysis included microbiologically confirmed cases of N.
      meningitidis in the blood and cerebrospinal fluid. There were 293 cases of
      confirmed MD during the study period. Two hundred and four cases (70%) were in
      children <= 14 years of age. The mean incidence rate was 0.5/100,000 persons. The
      dominant serogroups were W-135 and B, accounting for 80 cases (32%) each.
      Serogroup B accounted for 69/204 (34%) of all cases in children <= 14 years and
      serogroup A accounted for 36/89 40% of all adult cases. There were three
      outbreaks: 1987 (caused by serogroup A), 1989 (caused by serogroup W-135) and
      2002 (caused by serogroup B). The mean case fatality rate was 13.5%. In
      conclusion, despite childhood routine vaccination with ACYW-135 polysaccharide
      vaccine, infants and young children remain at high risk for MD, which supports
      the introduction of conjugate meningococcal vaccine to the routine childhood
      vaccination schedule.

PMID- 25779347
TI  - Electrochemical detection of aqueous Ag+ based on Ag+-assisted ligation reaction.
AB  - In this work, a novel strategy to fabricate a highly sensitive and selective
      biosensor for the detection of Ag(+) is proposed. Two DNA probes are designed and
      modified on a gold electrode surface by gold-sulfur chemistry and hybridization.
      In the presence of Ag(+), cytosine-Ag(+)-cytosine composite forms and facilitates
      the ligation event on the electrode surface, which can block the release of
      electrochemical signals labeled on one of the two DNA probes during denaturation
      process. Ag(+) can be sensitively detected with the detection limit of 0.1 nM,
      which is much lower than the toxicity level defined by U.S. Environmental
      Protection Agency. This biosensor can easily distinguish Ag(+) from other
      interfering ions and the performances in real water samples are also
      satisfactory. Moreover, the two DNA probes are designed to contain the
      recognition sequences of a nicking endonuclease, and the ligated DNA can thus be
      cleaved at the original site. Therefore, the electrode can be regenerated, which
      allows the biosensor to be reused for additional tests.

PMID- 25779348
TI  - Microchimerism in women with recurrent miscarriage.
AB  - Miscarriage is the most common pregnancy complication, and recurrent miscarriage
      (3 or more consecutive pregnancy losses) affects 1-5% of couples. Maternal-fetal
      exchange and the persistence of exchanged material as microchimerism appears to
      be disrupted in complicated pregnancies. We recently conducted a longitudinal
      cohort study of microchimerism in women with recurrent miscarriage. Our initial
      data raise multiple questions that require further investigation. Here, we review
      our data from this recent study and provide additional information regarding
      microchimerism in the granulocyte cell layer. This area of investigation offers a
      unique window into early reproductive events, and future related studies have the
      potential to identify novel therapeutic approaches and insights into human
      evolution. 

PMID- 25779350
TI  - Macrophage uptake of cylindrical microparticles investigated with correlative
      microscopy.
AB  - Cylindrical particles offer the opportunity to develop controlled and sustained
      release systems for the respiratory tract. One reason is that macrophages can
      phagocyte such particles only from either of the two ends. We investigated the
      uptake behaviour of murine alveolar macrophages incubated with elongated
      submicron-structured particles. For that purpose, fluorescent model silica
      nanoparticles were interconnected with the biocompatible polysaccharide agarose,
      building up cylindrical particles within the pores of track-etched membranes. In
      contrast to common approaches we determined the uptake at different time points
      with scanning electron microscopy, fluorescence microscopy, and the combination
      of both techniques - correlative microscopy (CLEM). As a consequence, we could
      securely identify uptake events and observe in detail the engulfment of particles
      and confirm, that phagocytosis could only be observed from the tips of the
      cylinders. CLEM allowed a comparison of the uptake measured with different
      techniques at identical macrophages. Qualitative and quantitative evaluation of
      this cylindrical particle uptake showed substantial differences between
      fluorescence microscopy, electron microscopy and the combination of both (CLEM)
      within 24h. 

PMID- 25779349
TI  - Conservation of transcription factor binding specificities across 600 million
      years of bilateria evolution.
AB  - Divergent morphology of species has largely been ascribed to genetic differences
      in the tissue-specific expression of proteins, which could be achieved by
      divergence in cis-regulatory elements or by altering the binding specificity of
      transcription factors (TFs). The relative importance of the latter has been
      difficult to assess, as previous systematic analyses of TF binding specificity
      have been performed using different methods in different species. To address
      this, we determined the binding specificities of 242 Drosophila TFs, and compared
      them to human and mouse data. This analysis revealed that TF binding
      specificities are highly conserved between Drosophila and mammals, and that for
      orthologous TFs, the similarity extends even to the level of very subtle
      dinucleotide binding preferences. The few human TFs with divergent specificities
      function in cell types not found in fruit flies, suggesting that evolution of TF
      specificities contributes to emergence of novel types of differentiated cells. 

PMID- 25779351
TI  - Measurement of low amounts of amorphous content in hydrophobic active
      pharmaceutical ingredients with dynamic organic vapor sorption.
AB  - Today, a variety of devices for dry powder inhalers (DPIs) is available and many
      different formulations for optimized deposition in the lung are developed.
      However, during the production of powder inhalers, processing steps may induce
      changes to both, the carrier and active pharmaceutical ingredients (APIs). It is
      well known that standard pharmaceutical operations may lead to structural
      changes, crystal defects and amorphous regions. Especially operations such as
      milling, blending and even sieving generate these effects. These disorders may
      induce re-crystallization and particle size changes post-production which have a
      huge influence on drug delivery and product stability. In this study, pilot tests
      with a polar solvent (water) and hydrophilic drug (Salbutamol sulfate) were
      performed to receive a first impression on further possible implementation of
      hydrophobic samples with organic solvents. Thereafter, a reliable method for the
      accurate detection of low amounts of amorphous content is described up to a limit
      of quantification (LOQ) of 0.5% for a hydrophobic model API (Ciclesonide). The
      organic vapor sorption method which is a gravimetric method quantifies exactly
      these low amounts of amorphous content in the hydrophobic powder once the
      suitable solvent (isopropanol), the correct p/p0 value (0.1) and the exact
      temperature (25 degrees C) have been found. Afterward it was possible to
      quantitate low amorphous amounts in jet-milled powders (0.5-17.0%). In summary,
      the data of the study led to a clearer understanding in what quantity amorphous
      parts were generated in single production steps and how variable these parts
      behave to fully crystalline material. Nevertheless it showed how difficult it was
      to re-crystallize hydrophobic material with water vapor over a short period. For
      the individual samples it was possible to determine the single humidity at which
      the material starts to re-crystallize, the behavior against different nonpolar
      solvents and the calculation of the reduction of the glass transition temperature
      (Tg) according to the Gordon-Taylor equation. 

PMID- 25779352
TI  - Injectable formulations for an intravitreal sustained-release application of a
      novel single-chain VEGF antibody fragment.
AB  - Sustained-release formulations of a single-chain anti-VEGF-A antibody fragment
      were investigated in vitro toward their potential use for intravitreal
      applications. The hydrophobic polyester hexylsubstituted poly(lactic acid)
      (hexPLA) was selected as the sustained-release excipient for its biodegradability
      and semi-solid aggregate state, allowing an easy and mild formulation procedure.
      The lyophilized antibody fragment ESBA903 was micronized and incorporated into
      the liquid polymer matrix by cryo-milling, forming homogeneous and injectable
      suspensions. The protein showed excellent compatibility with the hexPLA polymer
      and storage stability at 4 degrees C for 10 weeks. Additionally, hexPLA shielded
      the incorporated active substance from the surrounding medium, resulting in a
      better stability of ESBA903 inside the polymer than after its release in the
      buffer solution. Formulations of ESBA903 with hexPLA having drug loadings between
      1.25% and 5.0% and polymer molecular weights of 1500 g/mol, 2500 g/mol, 3500
      g/mol and 5000 g/mol were investigated regarding their in vitro release. All
      formulations except with the highest molecular weight formed spherical depots in
      aqueous buffer solutions and released the antibody fragment for at least 6-14
      weeks. The polymer viscosity derived from the molecular weight strongly
      influenced the release rate, while the drug loading had minor influence, allowing
      customization of the release profile and the daily drug release. Size exclusion
      chromatography and SDS-PAGE revealed that the antibody fragment structure was
      kept intact during incorporation and release from the liquid matrix. Furthermore,
      the released protein monomer maintained its high affinity to human VEGF-A, as
      measured by surface plasmon resonance analysis. Formulations of ESBA903 in hexPLA
      meet the basic needs to be used for intravitreal sustained-release applications
      in age-related macular degeneration treatment.

PMID- 25779353
TI  - PKC-mediated inhibitory feedback of the cholecystokinin 1 receptor controls the
      shape of oscillatory Ca2+ signals.
AB  - Translation of extracellular hormonal input into cellular responses is often
      mediated by repetitive increases in cytosolic free Ca(2+) concentration ([Ca(2+)
      ]c ). Amplitude, duration and frequency of these so-called [Ca(2+) ]c
      oscillations then carry information about the nature and concentration of the
      extracellular signalling molecule. At present, there are different hypotheses
      concerning the induction and control of these oscillations. Here, we investigated
      the role of agonist-induced receptor phosphorylation in this process using
      Chinese hamster ovary cells stably expressing a variant of the cholecystokinin 1
      receptor (CCK1R) lacking the four consensus sites for protein kinase C (PKC)
      phosphorylation and deficient in CCK-induced receptor phosphorylation (CCK1R-mt
      cells). In the presence of cholecystokinin-(26-33)-peptide amide (CCK-8), these
      cells displayed Ca(2+) oscillations with a much more pronounced bursting dynamics
      rather than the dominant spiking dynamics observed in Chinese hamster ovary cells
      stably expressing the wild-type CCK1R. The bursting behaviour returned to
      predominantly spiking behaviour following removal of extracellular Ca(2+) ,
      suggesting that CCK-8-induced, PKC-mediated CCK1R phosphorylation inhibits Ca(2+)
      influx across the plasma membrane. To gain mechanistic insight into the
      underlying mechanism we developed a mathematical model able to reproduce the
      experimental observations. From the model we conclude that binding of CCK-8 to
      the CCK1R leads to activation of PKC which subsequently phosphorylates the
      receptor to inhibit the receptor-mediated influx of Ca(2+) across the plasma
      membrane. Receptor-specific differences in this feedback mechanism may, at least
      in part, explain the observation that different agonists evoke [Ca(2+) ]c
      oscillations with different kinetics in the same cell type. 

PMID- 25779354
TI  - Controlled release of retinyl acetate from beta-cyclodextrin functionalized
      poly(vinyl alcohol) electrospun nanofibers.
AB  - Retinyl acetate (RA) was effectively incorporated into electrospun nanofibers of
      poly(vinyl alcohol) (PVA) containing beta-cyclodextrin (beta-CD) in order to form
      inclusion complexes for encapsulation to prolong shelf life and thermal
      stability. The physical and thermal properties of encapsulated RA were determined
      by scanning electron microscopy (SEM), X-ray diffraction (XRD), and differential
      scanning calorimetry (DSC). The nanofibers of PVA/RA and PVA/RA/beta-CD exhibited
      bead free average fiber diameters of 264 +/- 61 and 223 +/- 49 nm, respectively.
      The surface chemistry of the functional nanofibers was investigated by X-ray
      photoelectron spectroscopy (XPS). Thermogravimetric analysis (TGA) demonstrated
      different thermal stabilities between the bioactive and the polymer, with and
      without beta-CD. Square-wave voltammogram peak current changes were used to
      follow the release kinetics of RA from the nanofibers. Results indicate that RA
      coated inside PVA/beta-CD nanofibers was protected against oxidation much better
      than RA in PVA nanofibers and should extend the shelf life. In addition, RA
      encapsulated in the PVA/beta-CD had better thermal stability than PVA nanofibers.

PMID- 25779355
TI  - Impact of surgical ventricular reconstruction on sphericity index in patients
      with ischaemic cardiomyopathy: follow-up from the STICH trial.
AB  - AIMS: We sought to evaluate associations between baseline sphericity index (SI)
      and clinical outcome, and changes in SI after coronary artery bypass graft (CABG)
      surgery with or without surgical ventricular reconstruction (SVR) in ischaemic
      cardiomyopathy patients enrolled in the SVR study (Hypothesis 2) of the Surgical
      Treatment for Ischemic Heart Failure (STICH) trial. METHODS AND RESULTS: Among
      1000 patients in the STICH SVR study, we evaluated 546 patients (255 randomized
      to CABG alone and 291 to CABG + SVR) whose baseline SI values were available. SI
      was not significantly different between treatment groups at baseline. After 4
      months, SI had increased in the CABG + SVR group, but was unchanged in the CABG
      alone group (0.69 +/- 0.10 to 0.77 +/- 0.12 vs. 0.67 +/- 0.07 to 0.66 +/- 0.09,
      respectively; P < 0.001). SI did not significantly change from 4 months to 2
      years in either group. Although LV end-systolic volume and EF improved
      significantly more in the CABG + SVR group compared with CABG alone, the severity
      of mitral regurgitation significantly improved only in the CABG alone group, and
      the estimated LV filling pressure (E/A ratio) increased only in the CABG + SVR
      group. Higher baseline SI was associated with worse survival after surgery
      (hazard ratio 1.21, 95% confidence interval 1.02 - 1.43; P = 0.026). Survival was
      not significantly different by treatment strategy. CONCLUSION: Although SVR was
      designed to improve LV geometry, SI worsened after SVR despite improved LVEF and
      smaller LV volume. Survival was significantly better in patients with lower SI
      regardless of treatment strategy.

PMID- 25779356
TI  - Carboxymethyl starch/alginate microspheres containing diamine oxidase for
      intestinal targeting.
AB  - The association of carboxymethyl starch (CMS) and alginate is proposed as a novel
      matrix for the entrapment of bioactive agents in microspheres affording their
      protection against gastrointestinal degradation. In this study, the enzyme
      diamine oxidase (DAO) from white pea (Lathyrus sativus) was immobilized by
      inclusion in microspheres formed by ionotropic gelation of CMS/alginate by
      complexation with Ca(2+) . The association of CMS to alginate generated a more
      compact structure presenting a lesser porosity, thus decreasing the access of
      gastric fluid inside the microspheres and preventing the loss of entrapped
      enzyme. Moreover, the immobilized enzyme remained active and was able to oxidize
      the polyamine substrates even in the presence of degrading proteases of
      pancreatin. The inclusion yield in terms of entrapped protein was of about 82%
      95%. The DAO entrapped in calcium CMS/alginate beads retained up to 70% of its
      initial activity in simulated gastric fluid (pH 2.0). In simulated intestinal
      fluid (pH 7.2) with pancreatin, an overall retention of 65% of activity for the
      immobilized DAO was observed over 24 H, whereas in similar conditions the free
      enzyme was totally inactivated. Our project proposes the vegetal DAO as an
      antihistaminic agent orally administered to treat food histaminosis and colon
      inflammation. 

PMID- 25779357
TI  - A magnetic anti-cancer compound for magnet-guided delivery and magnetic resonance
      imaging.
AB  - Research on controlled drug delivery for cancer chemotherapy has focused mainly
      on ways to deliver existing anti-cancer drug compounds to specified targets,
      e.g., by conjugating them with magnetic particles or encapsulating them in
      micelles. Here, we show that an iron-salen, i.e., MU-oxo N,N'-
      bis(salicylidene)ethylenediamine iron (Fe(Salen)), but not other metal salen
      derivatives, intrinsically exhibits both magnetic character and anti-cancer
      activity. X-Ray crystallographic analysis and first principles calculations based
      on the measured structure support this. It promoted apoptosis of various cancer
      cell lines, likely, via production of reactive oxygen species. In mouse leg tumor
      and tail melanoma models, Fe(Salen) delivery with magnet caused a robust decrease
      in tumor size, and the accumulation of Fe(Salen) was visualized by magnetic
      resonance imaging. Fe(Salen) is an anti-cancer compound with magnetic property,
      which is suitable for drug delivery and imaging. We believe such magnetic anti
      cancer drugs have the potential to greatly advance cancer chemotherapy for new
      theranostics and drug-delivery strategies. 

PMID- 25779358
TI  - CD44 Variant 9 Serves as a Poor Prognostic Marker in Early Gastric Cancer, But
      Not in Advanced Gastric Cancer.
AB  - PURPOSE: The present study is to investigate the significance of CD44 variant 9
      (CD44v9) expression as a biomarker in primary gastric cancer. MATERIALS AND
      METHODS: With various gastric tissues, we performed immunohistochemical staining
      for CD44v9. RESULTS: The positive expression rates for CD44v9 in tumor, including
      adenoma, early gastric cancer (EGC), and advanced gastric cancer (AGC), were
      higher than those in non-tumor tissues (p=0.003). In addition, the higher
      expression for CD44v9 was observed as the tissue becomes malignant. In the
      analysis of 333 gastric cancer tissues, we found that positive expression rates
      for CD44v9 were higher in the intestinal type or well differentiated gastric
      cancer than in the diffuse type or poorly differentiated gastric cancer.
      Interestingly, the positive expression indicated poor prognosis in EGC (5-year
      survival rate [5-YSR] in stage I, 81.7% vs. 95.2%; p=0.013), but not in AGC (5
      YSR in stage II, 66.9% vs. 62.2%; p=0.821; 5-YSR in stage III, 34.5% vs. 32.0%;
      p=0.929). Moreover, strong positive expression (3+) showed a trend suggesting
      worse prognosis only in EGC, and it appeared to be associated with lymph node
      metastasis. CONCLUSION: This study suggests that CD44v9 may be a good biomarker
      for prognosis prediction and for chemoprevention or biomarker-driven therapies
      only for EGC.

PMID- 25779359
TI  - The Role of Plasma Chromogranin A as Assessment of Treatment Response in Non
      functioning Gastroenteropancreatic Neuroendocrine Tumors.
AB  - PURPOSE: Chromogranin A (CgA) has been considered to be valuable not only in the
      diagnosis but also in monitoring the disease response to treatment. However, only
      a few studies have been published on this issue. We purposed to evaluate whether
      biochemical response using plasma CgA level is reliable in concordance with the
      clinical response of grade 1-3 nonfunctiong gastroenteropancreatic neuroendocrine
      tumors (GEP-NETs). MATERIALS AND METHODS: Between March 2011 and September 2013,
      a total of 27 cases in 18 patients were analysed, clinically and radiologically
      while serial CgA tests were also conducted during treatment. Tumor responses were
      defined by both Response Evaluation Criteria in Solid Tumors (RECIST) criteria
      ver. 1.1 and biochemical criteria based on the CgA level. RESULTS: Among the 27
      cases analysed, no difference in the basal CgA level was observed with regard to
      gender, primary tumor site, tumor grade (World Health Organization
      classification), liver metastasis, number of metastatic site, and line of
      chemotherapy. The overall response rate (RR) by RECIST criteria ver. 1.1 was six
      out of the 27 cases (22.2%) and eight out of the 27 cases (29.6%) for biochemical
      RR. The overall concordance rates of the response based on RECIST and biochemical
      criteria were 74%. In grades 1 and 2 GEP-NETs (n=17), the concordance rate of the
      disease control was 94.1%. There was a significant difference for progression
      free survival (PFS) between responders and non-responder in accordance to
      biochemical criteria (35.73 months vs. 5.93 months, p=0.05). CONCLUSION: This
      study revealed that changes of the plasma CgA levels were associated with tumour
      response. Additionally, biochemical response based on serial CgA may be a
      predictive marker for PFS in GEP-NETs.

PMID- 25779360
TI  - Prediction of cancer incidence and mortality in Korea, 2015.
AB  - PURPOSE: For estimation of Korea's current cancer burden, this study aimed to
      report on the projected cancer incidence and mortality rates for the year 2015.
      MATERIALS AND METHODS: Cancer incidence data from 1999 to 2012 were obtained from
      the Korea National Cancer Incidence Database, and cancer mortality data from 1993
      to 2013 were acquired from Statistics Korea. The cancer incidence in 2015 was
      projected by fitting a linear regression model to the observed age-specific
      cancer incidence rates against the observed years and then multiplying the
      projected age-specific rates by the age-specific population. A similar procedure
      was used for cancer mortality, except a Joinpoint regression model was used to
      determine at which year the linear trend changed significantly. RESULTS: A total
      of 280,556 new cancer cases and 76,698 cancer deaths are expected to occur in
      Korea in 2015. The crude incidence rate per 100,000 of all sites combined will
      likely reach 551.6 and the age-standardized incidence rate, 347.6. The estimated
      five leading primary cancer incidence sites are the stomach, colorectum, lung,
      prostate, and liver in men; and thyroid, breast, colorectum, stomach, and lung in
      women. The projected crude mortality rate of all sites combined and age
      standardized rate is 150.8 and 82.4, respectively. CONCLUSION: Cancer is
      currently one of the foremost public health concerns in Korea, and as the
      population ages, the nation's cancer burden will continue to increase.

PMID- 25779361
TI  - Is Human Kallikrein 11 in Non-small Cell Lung Cancer Treated Chemoradiotherapy
      Associated with Survival?
AB  - PURPOSE: Involvement of human kallikreins (hKs) in human cancers has been
      reported and several hKs are promising biomarkers of various cancers. The aim of
      this study was to evaluate the prognostic significance of hK11 expression in
      patients with non-metastatic non-small cell lung cancer (NSCLC). MATERIALS AND
      METHODS: The study included 44 patients with NSCLC. hK11 expression was
      determined by immunohistochemical staining. RESULTS: The estimation of disease
      free and overall survival by Kaplan-Meier was 11 months and 17 months,
      respectively. The estimation of overall survival by Kaplan-Meier was
      significantly higher in patients with hK11 strongly positive (2+) than in those
      with hK11 weakly positive (1+) (20 months vs. 11 months, p=0.032). Although not
      statistically different, the estimation of disease-free survival by Kaplan-Meier
      was higher in patients with hK11 strongly positive (2+) than in those with hK11
      weakly positive (1+) (12 months vs. 9 months, p=0.113). Multivariate Cox
      regression analysis showed that the overall survival rates were significantly
      associated with response to chemoradiotherapy and the degree of staining with
      hK11. CONCLUSION: The stronger hK11 expression in NSCLC appears to be associated
      with better survival rates. hK11 may be a prognostic biomarker of NSCLC.

PMID- 25779362
TI  - The Impact of Diabetes Mellitus and Metformin Treatment on Survival of Patients
      with Advanced Pancreatic Cancer Undergoing Chemotherapy.
AB  - PURPOSE: A causal relationship between diabetes mellitus (DM) and pancreatic
      cancer is well established. However, in patients with advanced pancreatic cancer
      (APC) who receive palliative chemotherapy, the impact of DM on the prognosis of
      APC is unclear. MATERIALS AND METHODS: We retrospectively enrolled APC patients
      who received palliative chemotherapy between 2003 and 2010. The patients were
      stratified according to the status of DM, in accordance with 2010 DM criteria
      (American Heart Association/American Diabetes Association). DM at least 2 years'
      duration prior to diagnosis of APC was defined as remote-onset DM (vs. recent
      onset). RESULTS: Of the 349 APC patients, 183 (52.4%) had DM. Among the patients
      with DM, 160 patients had DM at the time of diagnosis of APC (remote-onset, 87;
      recent-onset, 73) and the remaining 23 patients developed DM during treatment of
      APC. Ultimately, 73.2% of patients (134/183) with DM received antidiabetic
      medication, including metformin (56 patients, 41.8%), sulfonylurea (62, 45.5%),
      and insulin (43, 32.1%). In multivariate analysis, cancer extent (hazard ratio
      [HR], 1.792; 95% confidence interval [CI], 1.313 to 2.445; p < 0.001) showed
      association with decreased overall survival (OS), whereas a diagnosis of DM (HR,
      0.788; 95% CI, 0.615 to 1.009; p=0.059) conferred positive tendency on the OS.
      Metformin treatment itself conferred better OS in comparison within DM patients
      (HR 0.693; 95% CI, 0.492 to 0.977; p=0.036) and even in all APC patients
      (adjusted HR, 0.697; 95% CI, 0.491 to 1.990; p=0.044). CONCLUSION: For APC
      patients receiving palliative chemotherapy, metformin treatment is associated
      with longer OS. Patients with DM tend to survive longer than those without DM.

PMID- 25779363
TI  - Definitive Chemoradiotherapy Versus Surgery Followed by Adjuvant Radiotherapy in
      Resectable Stage III/IV Hypopharyngeal Cancer.
AB  - PURPOSE: The purpose of this study is to compare the treatment outcomes for
      locally advanced resectable hypopharyngeal cancer between organ-preserving
      chemoradiotherapy (CRT) and surgery followed by radiotherapy (SRT). MATERIALS AND
      METHODS: We reviewed 91 patients with stage III/IV hypopharyngeal squamous cell
      carcinoma treated with radiotherapy (RT). In the CRT group (n=34), 18 patients
      were treated with concurrent CRT and 16 patients with induction chemotherapy plus
      concurrent CRT. In the SRT group (n=57), six patients were treated with total
      laryngopharyngectomy, 34 patients with total laryngectomy (TL) and partial
      pharyngectomy (PP), and 17 patients with PP, which were followed by adjuvant
      radiotherapy (n=41) or CRT (n=16). The median RT dose was 70 Gy for CRT and 59.4
      Gy for SRT. RESULTS: Five-year local control (84.1% vs. 90.9%), and disease-free
      survival (DFS, 51.0% vs. 52.7%) and overall survival (OS, 58.6% vs. 56.6%) showed
      no significant difference between the CRT and SRT groups. The functional larynx
      preservation rate was higher in the CRT group (88.2% vs. 29.8%). Treatment
      related toxicity, requiring surgical intervention, occurred more frequently in
      the SRT group (37% vs. 12%). In the SRT group, TL resulted in a significantly
      higher DFS than larynx-sparing surgery (63.9% vs. 26.5%, p=0.027). Treatment
      outcome of the SRT group improved when only patients with TL were considered
      (n=40); however, 5-year OS (67.1% vs. 58.6%, p=0.830) and DFS (63.9% vs. 51.0%,
      p=0.490) did not improve significantly when compared to the CRT group.
      CONCLUSION: Organ preserving CRT provided a treatment outcome that is comparable
      to SRT for locally advanced hypopharyngeal cancer, while offering an opportunity
      for functional larynx-preservation and reduced treatment-related toxicity.

PMID- 25779364
TI  - Can Anorectal Manometry Findings Predict Subsequent Late Gastrointestinal
      Radiation Toxicity in Prostate Cancer Patients?
AB  - PURPOSE: The purpose of this study is to investigate the influence of
      radiotherapy (RT) on anorectal function and radiation-induced toxicity in
      patients with prostate cancer. MATERIALS AND METHODS: Fifty-four patients who
      were treated with RT for prostate cancer (T1c-4N0-1M0) were evaluated. To assess
      the changes in anorectal function, two consecutive anorectal manometry readings
      were performed in patients, before and after 4-6 months of RT. Late
      gastrointestinal (GI) toxicity was defined as symptoms occurring more than 6
      months after RT. The median radiation dose was 70.0 Gy (range, 66.0 to 74.0 Gy).
      Whole pelvis field RT was performed in 16 patients (29.6%). Grade of late
      radiation toxicity was defined in accordance to the severity of symptoms
      (Gulliford's scoring system). RESULTS: The median follow-up period was 60 months.
      Resting anal pressure (p=0.001), squeeze pressure (p < 0.001), and urge to
      defecate volume (p=0.025) were significantly reduced after RT. Fourteen patients
      (25.9%) experienced late GI toxicities. Among them, nine (16.7%) showed severe
      (grade >= 2) late toxicities. Elevated resting and squeeze external anal
      sphincter pressure prior to RT and large urge to defecate volumes after RT were
      associated with the occurrence of late GI toxicities. CONCLUSION: RT caused
      symptomatic anorectal dysfunction and resulted in a weakened anal sphincter.
      Increased urge to defecate volumes after RT were related to late GI toxicities.
      Elevated resting and squeeze anal sphincter pressure prior to RT rodcan be used
      to identify patients with an increased risk of late GI toxicities.

PMID- 25779365
TI  - Sustaining Blood Lymphocyte Count during Preoperative Chemoradiotherapy as a
      Predictive Marker for Pathologic Complete Response in Locally Advanced Rectal
      Cancer.
AB  - PURPOSE: The objective of this study was to explore the relationship between the
      circulating lymphocyte level during preoperative chemoradiotherapy (CRT) and
      pathologic complete response (pCR) in locally advanced rectal cancer. MATERIALS
      AND METHODS: From May 2010 to May 2013, 52 patients treated with preoperative CRT
      followed by surgery, were analysed. Patients received conventional fractionated
      radiotherapy (50-54 Gy) with fluorouracil-based chemotherapy. Surgical resection
      was performed at 4 to 8 weeks after the completion of preoperative CRT. Absolute
      blood lymphocyte counts and their relative percentage in total white blood cell
      counts were obtained from complete blood count tests performed prior to and after
      4, 8, and 12 weeks of CRT. We analysed the association between achieving pCR and
      change in blood lymphocyte level during CRT, as well as clinical parameters.
      RESULTS: Among 52 patients, 14 (26.9%) had evidence of pCR. Sustaining the blood
      lymphocyte count during CRT (lymphocyte count at 4 weeks/baseline lymphocyte
      count > 0.35; odds ratio, 8.33; p=0.02) and initial carcinoembryonic antigen <
      4.4 ng/mL (odds ratio, 6.71; p=0.03) were significantly associated with pCR in
      multivariate analyses. CONCLUSION: Sustaining blood lymphocyte count during
      preoperative CRT was predictive for pCR in rectal cancer. Further studies are
      warranted to investigate the association between pathologic responses and
      circulating lymphocyte count with its subpopulation during preoperative CRT.

PMID- 25779366
TI  - Family Avoidance of Communication about Cancer: A Dyadic Examination.
AB  - PURPOSE: This study aimed to examine the following questions: to what extent do
      patients and caregivers perceive their family members to be avoidant of
      communication regarding patient's cancer, and to what extent do these perceptions
      interrelate; and how do such perceptions influence their own and each other's
      communication behaviors, communication outcome, mental health, and quality of
      life. MATERIALS AND METHODS: A national survey was performed with 990 patient
      caregiver dyads (participation rate, 76.2%). To examine the dyadic interaction,
      we developed linked patient and family member questionnaires, including the
      Family Avoidance of Communication about Cancer (FACC) scale. RESULTS: The mean
      scores (standard deviations) of patient- and caregiver-perceived FACC were low at
      10.9 (15.5) and 15.5 (17.5), respectively (p < 0.001), and concordance was low, a
      well (Spearman's rho, 0.23). Patient-perceived FACC was associated with lower
      levels of disclosure and behaviors of holding back communication, as well as
      lower levels of mental health outcome and quality of life. The same was true for
      caregivers (all p < 0.05). Patient-perceived FACC was associated with caregiver
      holding back, caregiver's depression level, and caregiver quality of life (all p
      < 0.05). Both patient- and caregiver-perceived FACC were independently associated
      with communication difficulty within the family. CONCLUSION: Future research
      would benefit from the measurement of FACC from both patients and caregivers, and
      promote family intervention to enhance openness to communication, which would be
      helpful for improving mental health and quality of life for both patients and
      caregivers.

PMID- 25779367
TI  - Robotic Versus Laparoscopic Surgery for Rectal Cancer after Preoperative
      Chemoradiotherapy: Case-Matched Study of Short-Term Outcomes.
AB  - PURPOSE: Robotic surgery is expected to have advantages over laparoscopic
      surgery; however, there are limited data regarding the feasibility of robotic
      surgery for rectal cancer after preoperative chemoradiotherapy (CRT). Therefore,
      we evaluated the short-term outcomes of robotic surgery for rectal cancer.
      MATERIALS AND METHODS: Thirty-three patients with cT3N0-2 rectal cancer after
      preoperative CRT who underwent robotic low anterior resection (R-LAR) between
      March 2010 and January 2012 were matched with 66 patients undergoing laparoscopic
      low anterior resection (L-LAR). Perioperative clinical outcomes and pathological
      data were compared between the two groups. RESULTS: Patient characteristics did
      not differ significantly different between groups. The mean operation time was
      441 minutes (R-LAR) versus 277 minutes (L-LAR, p < 0.001). The open conversion
      rate was 6.1% in the R-LAR group and 0% in the L-LAR group (p=0.11). There were
      no significant differences in the time to flatus passage, length of hospital
      stay, and postoperative morbidity. In pathological review, the mean number of
      harvested lymph nodes was 22.3 in R-LAR and 21.6 in L-LAR (p=0.82). Involvement
      of circumferential resection margin was positive in 16.1% and 6.7%, respectively
      (p=0.42). Total mesorectal excision (TME) quality was complete in 97.0% in R-LAR
      and 91.0% in L-LAR (p=0.41). CONCLUSION: In our study, short-term outcomes of
      robotic surgery for rectal cancer after CRT were similar to those of laparoscopic
      surgery in respect to bowel function recovery, morbidity, and TME quality. Well
      designed clinical trials are needed to evaluate the functional results and long
      term outcomes of robotic surgery for rectal cancer.

PMID- 25779369
TI  - Supramolecular imidazolium frameworks: direct analogues of metal azolate
      frameworks with charge-inverted node-and-linker structure.
AB  - While azolate anions have been extensively used as anionic linkers in framework
      design, we now demonstrate the synthesis of square-grid networks that utilise
      their cationic analogues, imidazolium ions, as linkers. The resulting imidazolium
      frameworks are direct hydrogen-bonded analogues of square-grid metal azolates and
      the first examples of an inverted polarity framework design based on anionic
      nodes and cationic linkers. 

PMID- 25779368
TI  - ZNF488 Enhances the Invasion and Tumorigenesis in Nasopharyngeal Carcinoma Via
      the Wnt Signaling Pathway Involving Epithelial Mesenchymal Transition.
AB  - PURPOSE: The purpose of this study was to investigate the function of Zinc finger
      protein 488 (ZNF488) in nasopharyngeal carcinoma (NPC). MATERIALS AND METHODS:
      The endogenous expression of ZNF488 in NPC tissues, normal nasopharyngeal
      epithelium tissues and NPC cell lines were detected by quantitative reverse
      transcription polymerase chain reaction. ZNF488 over-expressing and knock-down
      NPC cell line models were established through retroviral vector pMSCV mediated
      over-expression and small interfering RNA (siRNA) mediated knock-down. The
      invasion and migration capacities were evaluated by wound healing and transwell
      invasion assays in ZNF488 over-expressing and control cell lines. Soft-agar
      colony formation and a xenograft experiment were performed to study tumorigenic
      ability in vitro and in vivo. Immunofluorescence and western blotting analysis
      were used to examine protein changes followed by ZNF488 over-expression.
      Microarray analysis was performed to explore gene expression profilings, while
      luciferase reporter assay to evaluate the transcriptive activity of Tcf/Lef.
      RESULTS: ZNF488 was over-expressed in NPC tissues compared with normal tissues,
      especially higher in 5-8F and S18, which are well-established high metastatic NPC
      clones. Functional studies indicate that over-expression of ZNF488 provokes
      invasion, whereas knock-down of ZNF488 alleviates invasive capability. Moreover,
      over-expression of ZNF488 promotes NPC tumor growth both in vitro and in vivo.
      Our data further show that over-expression of ZNF488 induces epithelial
      mesenchymal transition (EMT) by activating the WNT/beta-catenin signaling
      pathway. CONCLUSION: Our data strongly suggest that ZNF488 acts as an oncogene,
      promoting invasion and tumorigenesis by activating the Wnt/beta-catenin pathway
      to induce EMT in NPC.

PMID- 25779370
TI  - Genetic and epigenetic associations to obesity-related appetite phenotypes among
      African-American children.
AB  - BACKGROUND: Genetic and epigenetic variations may be an important contributer to
      altered eating behaviors in childhood which may lead to weight gain and obesity
      later in life. OBJECTIVE: This study aimed to evaluate epigenetic as well as
      genetic associations with appetite in young children. SUBJECTS AND METHODS:
      Participants were 32 non-obese and 32 obese African-American children aged 5-6
      years. Saliva was collected from each child, and RNA and DNA were extracted for
      analysis. Individuals were genotyped for eating- and obesity-associated single
      nucleotide polymorphisms in seven candidate genes (FTO, MAOA, SH2B1, LEPR,
      DNMT3B, BDNF and CCKAR), and DNA methylation levels were measured in the upstream
      promoter region of each. Transcript levels of MAOA and FTO were also assessed.
      The Children's Eating Behavior Questionnaire (CEBQ) was used to assess the
      aspects of appetite. Child obesity was assessed using measured height and weight,
      and percent body fat was measured by dual-energy X-ray absorptiometry. RESULTS:
      Food responsiveness was higher and satiety responsiveness was lower among obese
      than non-obese female children (P = 0.001 and P = 0.031), but did not differ
      among male children. Epigenetic analysis of the BDNF promoter revealed
      associations with altered satiety responsiveness among female children (P <
      0.01). CONCLUSION: The findings provide new evidence of epigenetic associations
      with altered appetite among young African-American girls.

PMID- 25779371
TI  - Wolf's Isotopic Response: Varicella Within a Prior Immunization Reaction Site.
AB  - Wolf's isotopic response describes the occurrence of a dermatologic condition at
      the site of a prior healed unrelated condition. Our report details a case of
      varicella occurring as a secondary condition at the site of a prior immunization
      reaction; herpesvirus infection has not been reported as a secondary condition in
      cases of Wolf's isotopic response before. Current hypotheses favor the
      involvement of neurohormonal modulation of local immunity in response to various
      forms of injury as a model for explaining these phenomena. 

PMID- 25779372
TI  - New insights into organic-inorganic hybrid perovskite CH3NH3PbI3 nanoparticles.
      An experimental and theoretical study of doping in Pb2+ sites with Sn2+, Sr2+,
      Cd2+ and Ca2+.
AB  - This paper presents the synthesis of the organic-inorganic hybrid perovskite,
      CH3NH3PbI3, doped in the Pb(2+) position with Sn(2+), Sr(2+), Cd(2+) and Ca(2+).
      The incorporation of the dopants into the crystalline structure was analysed,
      observing how the characteristics of the dopant affected properties such as the
      crystalline phase, emission and optical properties. XRD showed how doping with
      Sn(2+), Sr(2+) and Cd(2+) did not modify the normal tetragonal phase. When doping
      with Ca(2+), the cubic phase was obtained. Moreover, DR-UV-Vis spectroscopy
      showed how the band gap decreased with the dopants, the values following the
      trend Sr(2+) < Cd(2+) < Ca(2+) < CH3NH3PbI3 ~ Sn(2+). The biggest decrease was
      generated by Sr(2+), which reduced the CH3NH3PbI3 value by 4.5%. In turn,
      cathodoluminescence (CL) measurements confirmed the band gap obtained. Periodic
      DFT calculations were performed to understand the experimental structures. The
      DOS analysis confirmed the experimental results obtained using UV-Vis
      spectroscopy, with the values calculated following the trend Sn(2+) ~ Pb(2+) >
      Cd(2+) > Sr(2+) for the tetragonal structure and Pb(2+) > Ca(2+) for the cubic
      phase. The electron localization function (ELF) analysis showed similar electron
      localizations for undoped and Sn(2+)-doped tetragonal structures, which were
      different from those doped with Sr(2+) and Cd(2+). Furthermore, when Cd(2+) was
      incorporated, the Cd-I interaction was strengthened. For Ca(2+) doping, the Ca-I
      interaction had a greater ionic nature than Cd-I. Finally, an analysis based on
      the non-covalent interaction (NCI) index is presented to determine the weak-type
      interactions of the CH3NH3 groups with the dopant and I atoms. To our knowledge,
      this kind of analysis with these hybrid systems has not been performed
      previously. 

PMID- 25779373
TI  - Integrated assessment of biomarker response in carp (Cyprinus carpio) and silver
      catfish (Rhamdia quelen) exposed to clomazone.
AB  - Clomazone is considered a potential contaminant of groundwater and is persistent
      in the environment. To verify the effects of clomazone in Cyprinus carpio and
      Rhamdia quelen, a method that combines biomarker responses into an index of
      "integrated biomarker response" (IBR) was used for observed biological
      alterations in these species. Thiobarbituric acid-reactive substances in liver of
      carp and silver catfish decreased at both concentrations tested. However, in
      muscle it increased in carp at 3 mg/L and silver catfish at 6 mg/L. Protein
      carbonyl increased in liver (3 and 6 mg/L) and muscle (6 mg/L) of carp. In carp,
      superoxide dismutase (SOD) increased at 3 mg/L and catalase at 6 mg/L. In silver
      catfish, SOD in liver decreased at 3 mg/L. Glutathione-S-transferase increased at
      3 mg/L in muscle of carp. Nonprotein thiol levels decreased at both
      concentrations in liver of silver catfish and muscle of carp. In silver catfish,
      acetylcholinesterase (AChE) decreased in brain at 6 mg/L. Nevertheless, AChE in
      muscle of both species increased at 3 and 6 mg/L. IBR was standardized scores of
      biomarker responses and was visualized using star plots. The IBR values shown
      that in carp there was predominantly an induction of parameters, whereas in
      silver catfish there was inhibition of these responses. In this way, IBR may be a
      practical tool for the identification of biological alterations in fish exposed
      to pesticides. In the present study, IBR was efficient for comparisons of fish
      species using clomazone. This study may serve as a base for evaluation of other
      pesticides in the rice field, environment, or laboratory experiment.

PMID- 25779375
TI  - Bonding charge density from atomic perturbations.
AB  - Charge transfer among individual atoms is the key concept in modern electronic
      theory of chemical bonding. In this work, we present a first-principles approach
      to calculating the charge transfer. Based on the effects of perturbations of an
      individual atom or a group of atoms on the electron charge density, we determine
      unambiguously the amount of electron charge associated with a particular atom or
      a group of atoms. We computed the topological electron loss versus gain using
      ethylene, graphene, MgO, and SrTiO3 as examples. Our results verify the nature of
      chemical bonds in these materials at the atomic level.

PMID- 25779374
TI  - Genome-wide analysis of cancer cell-derived Foxp3 target genes in human tongue
      squamous cell carcinoma cells.
AB  - The forkhead transcription factor Foxp3 is essential for differentiation and
      activation of regulatory T cells (Tregs), and used to be regarded as specific
      transcription factor of Tregs. In recent years, Foxp3 expression in tumor cells
      (cancer cell-derived Foxp3) has gained great interest, but its function and
      molecular mechanisms remain incompletely understood. In the present study, we
      detected dynamic nuclear translocation of Foxp3 in TSCC cells using
      immunofluorescent staining. Then we performed a genome-wide analysis of Foxp3 in
      TSCC cells using a combination of ChIP-on-chip and whole-genome microarray
      assays. We also compared Foxp3 biding sites in TSCC cells with the known binding
      sites in human Tregs to show the differences in transcriptional regulation
      profile. Results indicate that Foxp3 in TSCC cells has distinct biological
      functions compared with that in Tregs. Cancer cell-derived Foxp3 directly
      regulates the transcription of genes that affect certain internal biological
      processes of TSCC cells, and indirectly influences the extracellular
      microenvironment. This study reveals the relationship between direct and indirect
      targets genes of Foxp3 in TSCC cells and provide molecular basis of cancer cell
      derived Foxp3 function.

PMID- 25779376
TI  - The cytological features of NPM1-mutated acute myeloid leukemia.

PMID- 25779377
TI  - Teenagers in England to be vaccinated against meningitis group W.

PMID- 25779378
TI  - Association between abortion and breast cancer: an updated systematic review and
      meta-analysis based on prospective studies.
AB  - OBJECTIVE: Although positive association between abortion and breast cancer was
      frequently reported from case-control studies, results from prospective studies
      were still unclear. This study aimed to evaluate this association based on
      prospective studies. METHODS: PubMed, ISI Web of Knowledge and Embase were
      systematically searched for prospective studies on the association between
      abortion and breast cancer up to April 2014, supplemented by manual searches on
      the references. Two reviewers independently conducted the literature search,
      study selection, data extraction, and quality assessment of included studies.
      Random effects models were used to estimate the combined relative risks (RRs) and
      corresponding 95 % confidence intervals (95 % CIs). RESULTS: Fifteen prospective
      studies [14 focused on induced abortion (IA), and 12 focused on spontaneous
      abortion (SA)] were included in the final analysis. The combined RRs (95 % CIs)
      of breast cancer risk were 1.00 (0.94-1.05) [1.00 (0.92-1.08) for cumulative
      incidence data and 1.00 (0.94-1.05) for incidence-rate data] for IA, and 1.02
      (0.95-1.09) [1.06 (0.96-1.16) for cumulative-incidence data and 1.01 (0.92-1.09)
      for incidence-rate data] for SA, respectively. Non-significant associations of
      breast cancer with IA and SA were also found among nulliparous women, women with
      abortion before or after the first full-term pregnancy, women with one or >= 2
      abortions, and women with first abortion after 30 years old. CONCLUSION: The
      current prospective evidences are not sufficient to support the positive
      association between abortion (including IA and SA) and breast cancer risk.

PMID- 25779379
TI  - Breast cancer screening of underserved women in the USA: results from the
      National Breast and Cervical Cancer Early Detection Program, 1998-2012.
AB  - OBJECTIVE: To describe the number and proportion of eligible women receiving
      mammograms funded by the National Breast and Cervical Cancer Early Detection
      Program (NBCCEDP). METHODS: Low-income, uninsured, and underinsured women aged 40
      64 are eligible for mammography screening through the NBCCEDP. We used data from
      the NBCCEDP, the Current Population Survey, and Medical Expenditure Panel Survey
      to describe the number and proportion of women screened by the NBCCEDP and
      overall. RESULTS: In 2011 and 2012, the NBCCEDP screened 549,043 women aged 40
      64, an estimated 10.6 % (90 % confidence interval [CI] 10.4-10.9 %) of the
      eligible population. We estimate that 30.6 % (90 % CI 26.4-34.8 %) of eligible
      women aged 40-64 were screened outside the NBCCEDP, and 58.8 % (90 % CI 54.6-63.0
      %) were not screened. The proportion of eligible women screened by the NBCCEDP
      varied across states, with an estimated range of 3.2 % (90 % CI 2.9-3.5 %) to
      52.8 % (90 % CI 36.1-69.6 %) and a median of 13.7 % (90 % CI 11.0-16.4 %). The
      estimated proportion of eligible women aged 40-64 who received mammograms through
      the NBCCEDP was relatively constant over time, 11.1 % (90 % CI 10.2-11.9 %) in
      1998-1999 and 10.6 % (90 % CI 10.4-11.9 %) in 2011-2012 (p = 0.23), even as the
      number of women screened increased from 343,692 to 549,043. CONCLUSIONS: Although
      the NBCCEDP provided screening services to over a half million low-income
      uninsured women for mammography, it served a small percentage of those eligible.
      The majority of low-income, uninsured women were not screened.

PMID- 25779380
TI  - Childhood lymphoma incidence patterns by ICCC-3 subtype in Mexico City
      metropolitan area population insured by Instituto Mexicano del Seguro Social,
      1996-2010.
AB  - PURPOSE: We reviewed the childhood lymphomas epidemiological data for the Mexico
      City metropolitan area (MCMA). METHODS: Data analysis from children (0-14 years
      old) diagnosed with lymphoma during the period 1996-2010 was performed at the
      Mexican Childhood Cancer Registry. Histological subtype was determined according
      to the International Classification of Childhood Cancer 3 (ICCC-3). Age-adjusted
      incidence rates were calculated per 1,000,000 children/year by age, gender, and
      ICCC-3 subtype; trends, by average annual percent change (AAPC). RESULTS: A total
      of 328 lymphoma cases included in the study had an incidence rate of 11.8,
      showing a decreasing trend [AAPC: -3.5; CI 95% (-5.9, -1.0)], primarily due to
      non-Hodgkin lymphomas (NHL) and Hodgkin lymphoma (HL) mixed cellularity subtype.
      NHL had the major incidence (5.8), with the precursor cell subtype being the most
      frequent (38.3%). Nodular sclerosis was the most frequent HL subtype. The
      incidence of Burkitt lymphoma was low (1.3). During the study period, there was
      an important reduction in the not-otherwise-specified subtype of NHL, which
      translated into a relative increase in the IIb3 subtype [AAPC: 7.3 (1.2, 13.8)].
      Low incidences of NHL and of HL and NHL were found for < 1-year-olds and for 10-
      to 14-year-olds, respectively. Incidence rates for children in the MCMA,
      particularly the < 1 and 10-14 age groups, were lower than those for developed
      countries. The overall male/female ratio was 2.3. CONCLUSIONS: There was a trend
      toward a reduced incidence, for some lymphoma subtypes, in particular for NOS
      lymphomas, which may be the result of improvement in diagnostic techniques.

PMID- 25779381
TI  - Crossing the Atlantic: the Euro-Lupus Nephritis regimen in North America.

PMID- 25779382
TI  - Marital Quality and Health in Middle and Later Adulthood: Dyadic Associations.
AB  - OBJECTIVES: We investigated associations between positive marital quality and
      health among married persons aged 50 or older and their spouses. Prior research
      using data from married individuals has yielded inconsistent findings regarding
      the association between positive marital quality and global health outcomes. The
      present study involved married couples to examine how spouses' positive marital
      quality affect their own and each other's health, and whether these effects vary
      by age. METHODS: Using data from 3 waves of the Health and Retirement Study
      (2006, 2008, 2010), we estimated a series of actor-partner interdependence models
      using mixed linear models. RESULTS: Analyses found that over the 4-year period
      (2006-2010) increases in positive marital quality of both spouses were
      independently associated with increases in their self-rated health in midlife and
      old age as well as with declines in disability in old age. Increases in positive
      marital quality were also linked with declines in functional limitations for
      middle-aged and older adults. DISCUSSION: Being perceived as a supportive spouse,
      as well as perceiving one's partner as such, has significant health implications.
      Overall, positive marital quality of both spouses contributes to health
      protection for middle-aged and older spouses.

PMID- 25779383
TI  - Immunological failure of first-line and switch to second-line antiretroviral
      therapy among HIV-infected persons in Tanzania: analysis of routinely collected
      national data.
AB  - OBJECTIVES: Rates of first-line treatment failure and switches to second-line
      therapy are key indicators for national HIV programmes. We assessed immunological
      treatment failure defined by WHO criteria in the Tanzanian national HIV
      programme. METHODS: We included adults initiating first-line therapy in 2004-2011
      with a pre-treatment CD4 count, and >=6-months of follow-up. We assessed
      subhazard ratios (SHR) for immunological treatment failure, and subsequent switch
      to second-line therapy, using competing risks methods to account for deaths.
      RESULTS: Of 121 308 adults, 7% experienced immunological treatment failure, and
      2% died without observed immunological treatment failure, over a median 1.7
      years. The 6-year cumulative probability of immunological treatment failure was
      19.0% (95% CI 18.5, 19.7) and of death, 5.1% (4.8, 5.4). Immunological treatment
      failure predictors included earlier year of treatment initiation (P < 0.001),
      initiation in lower level facilities (SHR = 2.23 [2.03, 2.45] for dispensaries
      vs. hospitals), being male (1.27 [1.19, 1.33]) and initiation at low or high CD4
      counts (for example, 1.78 [1.65, 1.92] and 5.33 [4.65, 6.10] for <50 and >=500
      vs. 200-349 cells/mm(3) , respectively). Of 7382 participants in the time-to
      switch analysis, 6% switched and 5% died before switching. Four years after
      immunological treatment failure, the cumulative probability of switching was 7.3%
      (6.6, 8.0) and of death, 6.8% (6.0, 7.6). Those who immunologically failed in
      dispensaries, health centres and government facilities were least likely to
      switch. CONCLUSIONS: Immunological treatment failure rates and unmet need for
      second-line therapy are high in Tanzania; virological monitoring, at least for
      persons with immunological treatment failure, is required to minimise unnecessary
      switches to second-line therapy. Lower level government health facilities need
      more support to reduce treatment failure rates and improve second-line therapy
      uptake to sustain the benefits of increased coverage.

PMID- 25779384
TI  - Comparative Cytotoxicity of Glycyrrhiza glabra Roots from Different Geographical
      Origins Against Immortal Human Keratinocyte (HaCaT), Lung Adenocarcinoma (A549)
      and Liver Carcinoma (HepG2) Cells.
AB  - Glycyrrhiza glabra L. (Fabaceae), commonly known as 'liquorice', is a well-known
      medicinal plant. Roots of this plant have long been used as a sweetening and
      flavouring agent in food and pharmaceutical products, and also as a traditional
      remedy for cough, upper and lower respiratory ailments, kidney stones, hepatitis
      C, skin disorder, cardiovascular diseases, diabetes, gastrointestinal ulcers and
      stomach ache. Previous pharmacological and clinical studies have revealed its
      antitussive, antiinflammatory, antiviral, antimicrobial, antioxidant,
      immunomodulatory, hepatoprotective and cardioprotective properties. While
      glycyrrhizin, a sweet-tasting triterpene saponin, is the principal bioactive
      compound, several bioactive flavonoids and isoflavonoids are also present in the
      roots of this plant. In the present study, the cytotoxicity of the methanol
      extracts of nine samples of the roots of G. glabra, collected from various
      geographical origins, was assessed against immortal human keratinocyte (HaCaT),
      lung adenocarcinoma (A549) and liver carcinoma (HepG2) cell lines using the in
      vitro 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazoliumbromide cell
      toxicity/viability assay. Considerable variations in levels of cytotoxicity were
      observed among various samples of G. glabra.

PMID- 25779385
TI  - High performing and stable supported nano-alloys for the catalytic hydrogenation
      of levulinic acid to gamma-valerolactone.
AB  - The catalytic hydrogenation of levulinic acid, a key platform molecule in many
      biorefinery schemes, into gamma-valerolactone is considered as one of the pivotal
      reactions to convert lignocellulose-based biomass into renewable fuels and
      chemicals. Here we report on the development of highly active, selective and
      stable supported metal catalysts for this reaction and on the beneficial effects
      of metal nano-alloying. Bimetallic random alloys of gold-palladium and ruthenium
      palladium supported on titanium dioxide are prepared with a modified metal
      impregnation method. Gold-palladium/titanium dioxide shows a marked,~27-fold
      increase in activity (that is, turnover frequency of 0.1 s(-1)) compared with its
      monometallic counterparts. Although ruthenium-palladium/titanium dioxide is not
      only exceptionally active (that is, turnover frequency of 0.6 s(-1)), it shows
      excellent, sustained selectivity to gamma-valerolactone (99%). The dilution and
      isolation of ruthenium by palladium is thought to be responsible for this
      superior catalytic performance. Alloying, furthermore, greatly improves the
      stability of both supported nano-alloy catalysts.

PMID- 25779386
TI  - The Take-Up of Employer-Sponsored Insurance Among Americans with Mental
      Disorders: Implications for Health Care Reform.
AB  - Little is known about how take-up of private health insurance coverage differs
      between those with and without mental disorders. This study seeks to fill this
      gap by using data from the 2004-2008 Medical Expenditure Panel Survey to examine
      differences in offers and take-up of employer-sponsored insurance (ESI) among
      adults aged 27-54. Little evidence that mental disorders are associated with take
      up of offers of ESI coverage was found. This suggests that take-up rates in the
      Affordable Care Act (ACA) marketplaces by those with and without mental disorders
      may be similar. The ACA is especially important to Americans with mental
      disorders, many of whom lack access to ESI coverage to pay for mental health
      treatment either through their own job or through a spouse's job. 

PMID- 25779387
TI  - Preferences and Barriers to Care Following Psychiatric Hospitalization at Two
      Veterans Affairs Medical Centers: A Mixed Methods Study.
AB  - Patient preferences and barriers to care may impact receipt of adequate mental
      health treatment following psychiatric hospitalization and could inform quality
      improvement initiatives. This study assessed preferences for a broad range of
      post-hospital services and barriers to counseling by surveying 291 patients and
      interviewing 25 patients who had recently been discharged from an inpatient
      psychiatric stay at one of the two Veterans Affairs Medical Centers. Individual
      counseling was the most frequently reported service that survey respondents
      preferred, but did not receive; whereas, open-ended survey responses and
      interviews also identified telephone follow-up "check-in" calls as a frequently
      preferred service. Difficulty with transportation was the most commonly cited
      barrier to counseling among survey respondents and in interviews; however,
      patients strongly preferred in-person counseling to telephone or internet-video
      alternatives. Increasing support from family and support from an individual
      Veteran peer were also perceived to be helpful in the majority of survey
      respondents. 

PMID- 25779424
TI  - An atlas of gastric PIWI-interacting RNA transcriptomes and their utility for
      identifying signatures of gastric cancer recurrence.
AB  - The poor survival and recurrence rate in gastric adenocarcinoma highlights the
      need for cancer gene discovery. Towards this end, we globally assessed the
      expression of an emerging class of small non-coding RNAs, called PIWI-interacting
      RNAs (piRNAs). We analysed the transcriptomes of 358 non-malignant stomach tissue
      and gastric adenocarcinoma samples, and found that nearly half of the expressed
      piRNAs were overexpressed in tumours. Our gastric piRNA atlas showed that most
      piRNAs were embedded in protein-coding sequences rather than known piRNA
      clusters. Furthermore, we identified a three-piRNA signature associated with
      recurrence-free survival. In this proof-of-principle study, we demonstrate the
      potential clinical utility of piRNAs in gastric cancer. 

PMID- 25779457
TI  - Optical trapping of interfaces at ultra-low interfacial tension.
AB  - We achieve active control of interfacial phenomena by optically trapping the
      interface using the gradient forces of a strongly focussed laser beam parallel to
      the interface. We illustrate our technique in a phase separated colloid-polymer
      mixture by distorting the interface in a very controlled way. The static
      structure of the manipulated interface as well as its dynamic relaxation
      behaviour are analysed. Both the statics and dynamics can be related to the
      capillary wave height-height correlation functions using the fluctuation
      dissipation theorem up to surprisingly large deformations of the interface. To
      underline the novelty and potential of our approach we also show multiple
      interface distortions and the controlled snap-off of liquid droplets. 

PMID- 25779425
TI  - Enterovirus 71 induces apoptosis of SH-SY5Y human neuroblastoma cells through
      stimulation of endogenous microRNA let-7b expression.
AB  - Enterovirus 71 (EV71) is a pathogenic microorganism that causes hand, foot and
      mouth disease. However, the epigenetic mechanisms behind how EV71 regulates host
      cell proliferation and apoptosis are unclear. In the present study, the ability
      of EV71 to induce apoptosis was analyzed in the SH-SY5Y human neuroblastoma cell
      line and the effect of this virus on the mRNA expression levels of various
      apoptotic markers, miRNA let-7b and cyclin D1 (CCND1), was also investigated. The
      results demonstrated that EV71 induced SH-SY5Y cell apoptosis. An MTT assay
      revealed a significant inhibitory effect of EV71 on cell proliferation between 12
      72 h post injection, compared with the control group. Furthermore, quantitative
      polymerase chain reaction and western blot analyses demonstrated that expression
      level of the apoptosis inhibitor Bcl-2 was markedly reduced, but the expression
      levels of the apoptosis-promoting factors Bax, caspase-7, caspase-3 and active
      caspase-3 were markedly higher in the SH-SY5Y cells 12-48 h after EV71 infection,
      compared with the non-infected cells. In addition, flow cytometric assays
      revealed that EV71 arrested the cell cycle of host SH-SY5Y cells. Northern blot
      analysis revealed a marked miRNA let-7b hybridization signal in the EV71 virus
      infected group compared with the non-infected group. Furthermore, western
      blotting confirmed that the CCND1 protein expression levels were significantly
      reduced in EV71-infected SH-SY5Y cells. EV71-inhibited SH-SY5Y proliferation was
      abrogated using let-7b specific 2'-O-Methyl-RNA, which inhibited endogenous miRNA
      let-7b expression. Thus, EV71 regulated the host SH-SY5Y cell cycle and cell
      proliferation via stimulating endo-genous miRNA let-7b and directly targeting
      CCND1, therefore EV71 is a potential candidate for antiviral therapy.

PMID- 25779458
TI  - Reproductive performance and reconception of Nellore cows according to their pure
      or cross-bred calves.
AB  - The objective of the present research was to evaluate the effect of a calf's
      genetic group on the productive and reproductive efficiency of its Nellore dam.
      Fixed-time artificial insemination was applied to 800 cows using semen extracted
      from Nellore, Simmental and Angus Red bulls. Four hundred eleven cows calved,
      producing 119 Nellore, 103 1/2Simmental-1/2Nellore and 189 1/2Nellore-1/2Angus
      Red calves. The second mating period, which paired Nellore cows with Simmental
      bulls, was initiated 10 days after parturitions began and lasted for 5 months.
      Based on the two successive parturitions, the cumulative parturition rate for
      calving periods of 3, 4 and 5 months was calculated. Although no significant
      difference was observed for birth weight among the genetic groups, cross-bred
      calves weighed, on average, 10% more than did pure-bred calves at the age of 205
      days. Nellore dams experienced a gestation period that was 7 days longer than did
      the cross-bred dams, and the former showed a higher parturition rate at 90 and
      120 days of the calving season, but not at 150 days (calving rates of 80.6, 76.4
      and 76.2% for mothers of Nellore, 1/2Nellore-1/2Angus Red and 1/2Nellore
      1/2Simmental, respectively, p > 0.05). At 90 and 120 days, Nellore dams produced
      more kg of calf per mated dam. In conclusion, in a short breeding season, Nellore
      dams nursing pure-bred Nellore calves were found to have a higher biological
      efficiency compared with Nellore dams nursing cross-bred calves. 

PMID- 25779459
TI  - Evaluating the mechanisms of change in motivational interviewing in the treatment
      of mental health problems: A review and meta-analysis.
AB  - Motivational interviewing (MI) has proven useful in the treatment of a variety of
      mental health problems, however the mechanisms of MI's success within these
      populations remain unknown. This review is a first attempt to investigate and
      meta-analyse MI mechanisms of change research conducted with participants who
      suffer mood, anxiety, psychotic, eating disorders, and comorbid conditions.
      Twenty studies met inclusion criteria and examined a range of potential MI
      mechanisms, including patient motivation and confidence, patient resistance, and
      engagement. Results indicated that while MI did not increase patient motivation
      more so than did comparison conditions, MI showed a favourable effect on patient
      engagement variables. However, medium to high levels of heterogeneity were
      detected for patient engagement, indicating significant differences between
      studies. Heterogeneity was somewhat explained through subgroup analyses examining
      the effect of comparison condition and participant diagnosis. Overall, there were
      few MI mechanisms of change available for review, though the results suggest that
      patient engagement with treatment may be a potential mechanism of change in
      populations diagnosed with anxiety, mood, and psychotic disorders. 

PMID- 25779460
TI  - Impulsivity and nonsuicidal self-injury: A review and meta-analysis.
AB  - Nonsuicidal self-injury (NSSI; direct self-injury without lethal intent) often is
      thought to be associated with impulse control problems. Recent research, however,
      offers conflicting results about whether impulsivity is a risk factor for NSSI
      engagement. To disentangle findings on the link between impulsivity and NSSI, an
      extensive review of the literature was conducted using several electronic
      databases (i.e., PsychInfo, PsychArticles, ERIC, CINAHL, and MEDLINE). In total,
      27 studies that met the specific inclusion criteria were identified. Results of a
      meta-analysis revealed that individuals who engaged in NSSI self-reported greater
      impulsivity than individuals who did not engage in NSSI, and that this effect was
      most consistent for measures of negative urgency. In contrast, there was little
      evidence of an association between lab-based measures of impulsivity (e.g., Go/No
      Go, Stop/Signal Task) and NSSI. Moreover, the link between impulsivity and NSSI
      found for self-report measures was sometimes eliminated when other risk factors
      for NSSI were controlled (e.g., abuse, depression, post-traumatic stress
      disorder). In addition to integrating findings, the present review provides
      several explanations for the discrepancies in findings between studies employing
      self-report versus lab-based measures of impulsivity. To conclude, several
      specific recommendations for future research directions to extend the literature
      on impulsivity and NSSI are offered. 

PMID- 25779461
TI  - SURVEY OF STAFF OPINIONS ABOUT EXTENDED HAEMODIALYSIS TREATMENT TIME AND SERVICE
      IMPLICATIONS.
AB  - BACKGROUND: We explored the potential impact of staff opinions and service
      provision upon patient's willingness to recruit to a clinical trial studying the
      effects of extended treatment time (TT) on haemodialysis (HD), six hours versus
      four hours for a period of twenty-four weeks. METHODS: We conducted a local
      survey of dialysis nurses and a national survey of multidisciplinary HD staff
      opinions to extended TT including clinical benefits, tolerance to, prescription
      and ability to accommodate extended TT on in-centre HD programmes. RESULTS: The
      survey was completed by 56/134 (42%) local nurses and the national survey by
      15/72 (21%) of dialysis providers across the UK (35% nurses and 75% other
      healthcare professionals). The majority of respondents felt extended TT was
      clinically beneficial but only 42% of nurses would recommend extended TT compared
      to 95% of non-nursing healthcare professionals (p < 0.0001). Although 45% of
      nurses felt that it was well tolerated, non-nursing healthcare professionals
      suggested this was significantly higher at 75% (p < 0.05). The negative impact on
      service provision was agreed by 83% of nurses with the need to facilitate shifts
      within a finite time period and pressure to find session spaces being cited.
      CONCLUSION: There is conflict between the understanding that extended TT is
      clinically beneficial and its prescription & delivery to patients. Enrolment to
      studies examining HD delivery strategies may be influenced by service provision
      and staff attitudes. In centre HD has been designed to maximise patient
      throughput and we may need to consider more flexible settings in which to deliver
      longer treatment time: Home HD maybe a solution.

PMID- 25779462
TI  - BTH treatment caused physiological, biochemical and proteomic changes of
      muskmelon (Cucumis melo L.) fruit during ripening.
AB  - Benzo-(1,2,3)-thiadiazole-7-carbothioic acid S-methyl ester (BTH) is a chemical
      plant elicitor capable of inducing disease resistance in many crops. In this
      study, the climacteric fruit muskmelon (cv. Yujinxiang) was treated with BTH at
      0.1g/L for assaying the changes in physiology, biochemistry and protein profile
      during ripening. The results showed that BTH treatment enhanced respiration rate,
      while reduced titratable acid content and retarded the decline of fruit firmness
      and ascorbic acid content. Ethylene production increased after BTH treatment at
      early stages of ripening, but decreased after 6days of treatment. Of the detected
      protein spots separated by means of 2-DE, 69 spots changed in abundance
      significantly after BTH treatment. Fifty-two spots out of 69 were identified
      using MALDI-TOF/TOF by blasting against NCBInr database. Functional
      classification revealed that the protein species identified were related to
      defense and stress responses, protein synthesis, destination and storage, energy
      metabolism, primary metabolism, cell structure, secondary metabolism, signal
      transduction and transporters. This study demonstrates an overview of major
      physiological, biochemical and proteomic changes in muskmelon fruit during
      ripening after BTH treatment and provides potentially useful information for
      maintaining fruit quality and delaying the ripening and senescence process.
      BIOLOGICAL SIGNIFICANCE: The study offers new proteomic evidences for elucidating
      the regulatory mechanism of muskmelon fruit ripening by BTH treatment at
      proteomic level, and provides a valuable reference for further research on the
      relationship between fruit quality and induction disease resistance in BTH
      treated fruits.

PMID- 25779463
TI  - Effects of heavy metals on Cyanothece sp. CCY 0110 growth, extracellular
      polymeric substances (EPS) production, ultrastructure and protein profiles.
AB  - The effects of several heavy metals on the growth/survival, EPS production,
      ultrastructure and protein profiles of the highly efficient extracellular
      polymeric substances (EPS)-producer cyanobacterium Cyanothece sp. CCY 0110 were
      evaluated. Our results clearly show that each heavy metal affects the cells in a
      particular manner, triggering distinctive responses. Concerning chronic exposure,
      cells were more affected by Cu(2+) followed by Pb(2+), Cd(2+), and Li(+). The
      presence of metal leads to remarkable ultrastructural changes, mainly at the
      thylakoid level. The comparison of the proteomes (iTRAQ) allowed to follow the
      stress responses and to distinguish specific effects related to the time of
      exposure and/or the concentration of an essential (Cu(2+)) and a non-essential
      (Cd(2+)) metal. The majority of the proteins identified and with fold changes
      were associated with photosynthesis, CO2 fixation and carbohydrate metabolism,
      translation, and nitrogen and amino acid metabolism. Moreover, our results
      indicate that during chronic exposure to sub-lethal concentrations of Cu(2+), the
      cells tune down their metabolic rate to invest energy in the activation of
      detoxification mechanisms, which eventually result in a remarkable recovery. In
      contrast, the toxic effects of Cd(2+) are cumulative. Unexpectedly, the amount of
      released polysaccharides (RPS) was not enhanced by the presence of heavy metals.
      BIOLOGICAL SIGNIFICANCE: This work shows the holistic effects of different heavy
      metals on the cells of the highly efficient EPS-producer the cyanobacterium
      Cyanothece sp. CCY 0110. The growth/survival, EPS production, ultrastructure,
      protein profiles and stress response were evaluated. The knowledge generated by
      this study will contribute to the implementation of heavy-metal removal systems
      based on cyanobacteria EPS or their isolated polymers.

PMID- 25779464
TI  - Methionine to isothreonine conversion as a source of false discovery
      identifications of genetically encoded variants in proteogenomics.
AB  - Searching deep proteome data for 9 NCI-60 cancer cell lines obtained earlier by
      Moghaddas Gholami et al. (Cell Reports, 2013) against a database from cancer
      genomes returned a variant tryptic peptide fragment 57-72 of molecular chaperone
      HSC70, in which methionine residue at 61 position is replaced by threonine, or
      isothreonine (homoserine), residue. However, no traces of the corresponding
      genetic alteration were found in the cell line genomes reported by Abaan et al.
      (Cancer Research, 2013). Studying on the background of this modification led us
      to conclude that a conversion of methionine into isothreonine resulted from
      iodoacetamide treatment of the probe during a sample preparation step. We found
      that up to 10% of methionine containing peptides experienced the above conversion
      for the datasets under study. The artifact was confirmed by model experiment with
      bovine albumin, where three of four methionine residues were partly converted to
      isothreonine by conventional iodoacetamide treatment. This experimental side
      reaction has to be taken into account when searching for genetically encoded
      peptide variants in the proteogenomics studies. BIOLOGICAL SIGNIFICANCE: A lot of
      effort is currently put into proteogenomics of cancer. Studies detect non
      synonymous cancer mutations at protein level by search of high-throughput LC
      MS/MS data against customized genomic databases. In such studies, much attention
      is paid to potential false positive identifications. Here we describe one
      possible cause of such false identifications, an artifact of sample preparation
      which mimics methionine to threonine nucleic acid-encoded variant. The methionine
      to isothreonine conversion should be taken into consideration for correct
      interpretation of proteogenomic data.

PMID- 25779465
TI  - Initial cognitive response to cholinesterase inhibitors and subsequent long-term
      course in patients with mild Alzheimer's disease.
AB  - BACKGROUND: Some guidelines recommend to discontinue treatment with
      cholinesterase inhibitors (ChEIs) in patients with Alzheimer's disease (AD)
      without an initial response to ChEI treatment. Evidence supporting this
      recommendation, however, is limited. This study aimed to investigate the relation
      between the initial cognitive response to ChEI treatment and the subsequent long
      term course of cognition of AD patients. METHODS: The Frisian Alzheimer's Disease
      Cohort study is a retrospective longitudinal study of 576 community-dwelling AD
      patients treated with ChEIs in a "real-life" setting at a large memory clinic. A
      repeated measures analysis using a marginal model (population based averaged
      model) was applied to investigate whether there is a difference in the subsequent
      long-term course of cognition (Mini-Mental State Examination (MMSE)) between
      initial non-responders and responders. Absence of an initial response was defined
      as a lower MMSE score after the first six months of treatment compared to
      baseline, a positive response as the same or a higher MMSE score. RESULTS: At
      baseline, median age was 80 years and the median MMSE score 23. Non-responders
      showed a slower rate of cognitive decline in the three subsequent years than
      responders, with a mean annual MMSE decline of 0.9 points versus 1.2 points,
      respectively (p < 0.0001). CONCLUSIONS: Our results suggest that it is not
      appropriate to discontinue ChEI treatment solely based on the absence of an
      initial cognitive response.

PMID- 25779466
TI  - Associations with publication and assessing publication bias in dementia
      diagnostic test accuracy studies.
AB  - OBJECTIVE: Biomarkers are of increasing interest in dementia research. Studies
      describing favourable accuracy of various dementia tests have influenced
      research, guidelines and diagnostic criteria. Publication bias is known to
      compromise reports on efficacy of therapeutic interventions. Traditional methods
      of quantifying publication bias are not suited to reviews of diagnostic tests. We
      aimed to describe rates and predictors of publication of dementia test accuracy
      studies presented at scientific meetings. METHODS: We chose three exemplar
      scientific meetings from 2009. Two independent researchers assessed conference
      proceedings and selected all abstracts relating to dementia diagnostics. We
      recorded basic descriptors and dichotomised results as 'positive' or 'neutral'.
      We assessed publication status using electronic literature databases and
      contacting lead authors. We described univariate and multivariate predictors of
      publication status using logistic regression modelling. RESULTS: From n = 2257
      abstracts, we identified n = 250 (11%) abstracts relating to dementia
      diagnostics. The majority n = 209 (84%) reported positive results. Only 97 (39%)
      of these studies are published. Univariate predictors of publication status
      included positive result (p = 0.042), North American or European authors (p =
      0.047), higher number of participants (p = 0.008) and use of a 'biomarker' test
      (p = 0.035). On multivariate analysis, only increasing number of participants was
      independently associated with publication (p = 0.034). CONCLUSIONS: Our strategy
      did not prove or disprove a publication bias effect in dementia test accuracy
      studies. The substantial proportion of 'positive' studies may point to a
      downstream 'submission bias' effect on decision to submit data to meetings.
      Modest rate of publication of dementia test accuracy studies is concerning, and
      publication bias remains possible.

PMID- 25779467
TI  - Quality of Life (QoL) Assessment in Patients with Neurofibromatosis Type 2 (NF2).
AB  - OBJECTIVE: The aim of this study was to develop a multidimensional metric for
      assessing quality of life (QoL) in patients with neurofibromatosis type 2 (NF2).
      STUDY DESIGN: Electronically distributed questionnaire. SETTING: University
      tertiary care hospital, NF2 support groups. SUBJECTS AND METHODS: Structured
      interviews with NF2 providers and patients identified relevant domains. Items in
      each domain were extracted from validated QoL modules, then combined with items
      unique to NF2 and pretested on NF2 providers and patients. The final 61-item
      questionnaire was administered electronically to patients with NF2 (N = 118). The
      form assessed overall QoL and 11 additional domains, including hearing, balance,
      facial function, vision, oral intake, future uncertainty, psychosocial,
      cognition, sexual activity, pain, and vocal communication. Responses were
      compared with reference values for the general population, patients with head and
      neck cancer, and patients with brain cancer. RESULTS: Overall, QoL in patients
      with NF2 was lower than that of the general population (P < .01) and similar to
      that of patients with cancer. Patients with more facial weakness, hearing loss,
      and imbalance reported significantly lower QoL. However, domains most predictive
      of overall QoL were psychosocial, future uncertainty, and pain. Compared with
      patients with head and neck and brain cancer, patients with NF2 demonstrated
      significantly higher levels of psychosocial stressors, including disease-related
      anxiety, personal and financial stress, and lack of social support (P < .01).
      CONCLUSION: Psychosocial stress and pain significantly affect QoL in NF2,
      indicating that mental health, pain management, and financial counseling could
      have an important impact on QoL in this population.

PMID- 25779468
TI  - Attitudes toward Human Papilloma Virus Vaccination and Head and Neck Cancer
      Prevention in a Diverse, Urban Population.
AB  - OBJECTIVE: (1) To understand if awareness of the human papilloma virus (HPV)
      vaccination's potential to prevent head and neck cancer improves acceptability of
      the vaccine in a large urban population and (2) to identify characteristics of
      those in whom such discussions would have the greatest impact. STUDY DESIGN: In
      person, anonymous survey. SETTING: Academic public hospital between March 2014
      and June 2014. SUBJECTS: Patients aged 12 to 24 years and their parents or
      guardians awaiting scheduled outpatient pediatric appointments. METHODS:
      Demographics and modified Carolina HPV Immunization Attitudes and Beliefs Scales
      data were cross-analyzed, followed by univariate binomial logistic regression to
      identify predictors for major outcomes of interest. RESULTS: More than 78% of
      those surveyed indicated they would be more receptive to the HPV vaccine if given
      strong evidence that it prevented head and neck cancer. Respondents were more
      likely to increase receptivity to HPV vaccination if they held the belief that
      they did not have enough information about the vaccine or indicated they
      preferred to wait because the vaccine was too new. CONCLUSION: Increasing public
      awareness of head and neck cancer prevention with HPV vaccination could increase
      HPV vaccination acceptance.

PMID- 25779469
TI  - Industry ties in otolaryngology: initial insights from the physician payment
      sunshine act.
AB  - OBJECTIVE: To characterize nonresearch payments made by industry to
      otolaryngologists in order to explore how the potential for conflicts of
      interests varies among otolaryngologists and compares between otolaryngologists
      and other surgical specialists. STUDY DESIGN: Retrospective cross-sectional
      database analysis. SETTING: Open Payments program database recently released by
      Centers for Medicare and Medicaid Services. SUBJECTS: Surgeons nationwide who
      were identified as receiving nonresearch payment from industry in accordance with
      the Physician Payment Sunshine Act. METHODS: The proportion of otolaryngologists
      receiving payment, the mean payment per otolaryngologist, and the standard
      deviation thereof were determined using the Open Payments database and compared
      to other surgical specialties. Otolaryngologists were further compared by
      specialization, census region, sponsor, and payment amount. RESULTS: Less than
      half of otolaryngologists (48.1%) were reported as receiving payments over the
      study period, the second smallest proportion among surgical specialties.
      Otolaryngologists received the lowest mean payment per compensated individual
      ($573) compared to other surgical specialties. Although otolaryngology had the
      smallest variance in payment among surgical specialties (SD, $2806), the
      distribution was skewed by top earners; the top 10% of earners accounted for 87%
      ($2,199,254) of all payment to otolaryngologists. Otolaryngologists in the West
      census region were less likely to receive payments (38.6%, P < .001). CONCLUSION:
      Over the study period, otolaryngologists appeared to have more limited financial
      ties with industry compared to other surgeons, though variation exists within
      otolaryngology. Further refinement of the Open Payments database is needed to
      explore differences between otolaryngologists and leverage payment information as
      a tool for self-regulation.

PMID- 25779470
TI  - The effect of radiotherapy on gentamicin ototoxicity: an animal model.
AB  - OBJECTIVE: Patients undergoing radiotherapy (RT) often present with serious
      bacterial infections requiring the use of antibiotic treatment. Gentamicin is a
      commonly used aminoglycoside antibiotic, whose ototoxicity remains a major
      problem in clinical use. The objective of this study was to determine whether
      radiation exposure can influence gentamicin-induced ototoxicity. STUDY DESIGN:
      Prospective animal study. SETTING: Animal care facilities of the Montreal
      Children's Hospital Research Institute. METHODS: Sixteen guinea pigs received low
      dose RT unilaterally for 4 weeks (total: 48 Gy). Animals then received low or
      high doses of gentamicin (40 mg/kg/d and 80 mg/kg/d) for 10 days. The ears were
      divided into 4 groups: gentamicin 40 mg, gentamicin 80 mg, gentamicin 40 mg + RT,
      and gentamicin 80 + RT. Auditory brainstem responses and distortion products
      otoacoustic emissions were assessed at baseline and before and after gentamicin
      treatment. Cochlear morphology using light and scanning electron microscopy were
      evaluated. RESULTS: High-dose gentamicin caused significant auditory brainstem
      response threshold shifts (P = .020), with greater hearing loss in the irradiated
      ear (difference of 23.6 + 7.5 dB). All animals exposed to high-dose gentamicin
      had head tilts toward the radiated side. Cochlear morphology revealed the
      greatest hair cell damage in the gentamicin 80 + RT group followed by gentamicin
      80. CONCLUSION: Results suggest that radiation can exacerbate the ototoxicity of
      gentamicin at high doses.

PMID- 25779471
TI  - Prolonged Radiant Exposure of the Middle Ear during Transcanal Endoscopic Ear
      Surgery.
AB  - Transcanal endoscopic ear surgery (EES) provides a high-resolution, wide-field
      view of the middle ear compared with the conventional operating microscope,
      reducing the need for a postauricular incision or mastoidectomy. Our group has
      shown in cadaveric human temporal bone studies that radiant energy from the
      endoscope tip can quickly elevate temperatures of the tympanic cavity. Elevated
      temperatures of the middle ear are associated with acute auditory brainstem
      response shifts in animal models. In EES, proposed methods to decrease middle ear
      temperature include frequent removal of the endoscope and the use of suction to
      rapidly dissipate heat; however, the routine application of such cooling
      techniques remains unknown. Herein, we aim to quantify the duration that the
      tympanic cavity is typically exposed to the endoscope during routine endoscopic
      middle ear surgery. We find that the tympanic cavity is exposed to the endoscope
      without a cooling mechanism for a prolonged period of time. 

PMID- 25779472
TI  - Development and characterization of chemical cochleostomy in the Guinea pig.
AB  - OBJECTIVES: Creation of an atraumatic, hearing-preservation cochleostomy is
      integral to the future of minimally invasive inner ear surgery. The goal of this
      study was to develop and characterize a novel chemical approach to cochleostomy.
      STUDY DESIGN: Prospective animal study. SETTING: Laboratory. METHODS:
      Experimental animal study in which phosphoric acid gel (PAG) was used to
      decalcify the otic capsule in 25 Hartley guinea pigs. Five animals in each of 5
      surgical groups were studied: (1) mechanically opening the auditory bulla alone,
      (2) PAG thinning of the basal turn otic capsule, leaving endosteum covered by a
      layer of bone, (3) micro-pick manual cochleostomy, (4) PAG chemical cochleostomy,
      exposing the endosteum, and (5) combined PAG/micro-pick cochleostomy, with
      initial chemical thinning and subsequent manual removal of the last osseous
      layer. Preoperative and postoperative auditory brainstem responses and
      otoacoustic emissions were obtained at 2, 6, 10, and 16 kHz. Hematoxylin and
      eosin-stained paraffin sections were compared. RESULTS: Surgical and histologic
      findings confirmed that application of PAG provided reproducible local bone
      removal, and cochlear access was enabled. Statistically significant auditory
      threshold shifts were observed at 10 kHz (P = .048) and 16 kHz (P = .0013)
      following cochleostomy using PAG alone (group 4) and at 16 kHz using manual
      cochleostomy (group 3) (P = .028). No statistically significant, postoperative
      auditory threshold shifts were observed in the other groups, including PAG
      thinning with manual completion cochleostomy (group 5). CONCLUSION: Hearing
      preservation cochleostomy can be performed in an animal model using a novel
      technique of thinning cochlear bone with PAG and manually completing
      cochleostomy.

PMID- 25779473
TI  - Assessment of the potential ototoxicity of high-dose celecoxib, a selective
      cyclooxygenase-2 inhibitor, in rats.
AB  - OBJECTIVE: To evaluate the potential ototoxicity of high-dose celecoxib, a
      selective cyclooxygenase-2 (COX-2) inhibitor. STUDY DESIGN: Prospective animal
      study. SETTING: Laboratory. METHODS: Twenty adult male Sprague Dawley rats were
      divided into 2 groups for hearing and tinnitus tests, respectively. The auditory
      brain-stem response (ABR) and the gap prepulse inhibition of acoustic startle
      (GPIAS) were used as indicators of hearing loss and tinnitus, respectively, and
      were measured before and at 2, 4, 6, 8, 12, 24, and 48 hours after administration
      of celecoxib (2 g/kg) via gavage. RESULTS: ABR threshold and wave III latencies
      did not increase significantly at any frequency following celecoxib
      administration, at any time point (P > .05). GPIAS remained below 30% after
      celecoxib, from a baseline of 20.03% +/- 3.62%; no change was significant.
      CONCLUSION: High-dose celecoxib (2 g/kg), a selective COX-2 inhibitor, did not
      cause hearing loss or tinnitus in Sprague Dawley rats within 48 hours of
      administration. Further studies are needed to explore the roles played by COX
      related mechanisms when nonselective COX inhibitors induce ototoxicity.

PMID- 25779474
TI  - Advances in stroke prevention.
AB  - Stroke remains to be a leading cause of disability. However, optimal strategies
      can prevent up to 80% of strokes. A large body of evidence supports many
      strategies for primary and secondary prevention of stroke. The purpose of this
      paper is to highlight recent major advances for management of modifiable medical
      and behavioral risk factors of stroke. Specific studies are highlighted,
      including those related to atrial fibrillation (AF), hypertension,
      revascularization, hyperlipidemia, antiplatelets, smoking, diet, and physical
      activity. Effective strategies include the use of novel oral anticoagulants for
      AF, antiplatelet therapy, and intensive lowering of atherosclerosis risk factors.

PMID- 25779476
TI  - Introduction to the year in neurology and psychiatry.

PMID- 25779477
TI  - [Severe fat embolism in perioperative abdominal liposuction and fat grafting].
AB  - BACKGROUND AND OBJECTIVES: Fat embolism syndrome (FES) may occur in patients
      suffering from multiple trauma (long bone fractures) or plastic surgery
      (liposuction), compromising the circulatory, respiratory and/or central nervous
      systems. This report shows the evolution of severe FES after liposuction and fat
      grafting. CASE REPORT: SSS, 42 years old, ASA 1, no risk factors for thrombosis,
      candidate for abdominal liposuction and breast implant prosthesis. Subjected to
      balanced general anesthesia with basic monitoring and controlled ventilation.
      After 45minutes of procedure, there was a sudden and gradual decrease of
      capnometry, severe hypoxemia and hypotension. The patient was immediately
      monitored for MAP and central catheter, treated with vasopressors, inotropes, and
      crystalloid infusion, stabilizing her condition. Arterial blood sample showed pH
      = 7.21; PCO2 = 51mmHg; PO2 = 52mmHg; BE = -8; HCO3 = 18 mEq/L, and lactate = 6.0
      mmol/L. Transthoracic echocardiogram showed PASP = 55mmHg, hypocontractile VD and
      LVEF = 60%. Diagnosis of pulmonary embolism. After 24h of intensive treatment,
      the patient developed anisocoria and coma (glasgow coma scale = 3). A brain CT
      was performed which showed severe cerebral hemispheric ischemia with signs of fat
      emboli in right middle cerebral artery; transesophageal echocardiography showed a
      patent foramen ovale. Finally, after 72h of evolution, the patient progressed to
      brain death. CONCLUSION: FES usually occurs in young people. Treatment is based
      mainly on the infusion of fluids and vasoactive drugs, mechanical ventilation,
      and triggering factor correction (early fixation of fractures or suspension of
      liposuction). The multiorganico involvement indicates a worse prognosis.

PMID- 25779478
TI  - Proteasome inhibitors and IMiDs can overcome some high-risk cytogenetics in
      multiple myeloma but not gain 1q21.
AB  - Chromosomal aberrations have significant prognostic importance in multiple
      myeloma (MM). However, proteasome inhibitors (PI) and IMiDs may partly overcome
      the poor prognostic impact of some of them. In this study, we investigated a
      population-based consecutive cohort newly diagnosed patients with MM admitted
      during a defined time period to hospitals in Denmark, Norway, and Sweden. The
      impact of treatment modality on the prognostic importance of specific chromosomal
      aberration was investigated, with special reference to gain 1q21. The median
      follow-up of patients still alive at analysis was 40 months for the high-dose
      (HDT)-treated ones and 29 months for the whole population. Three hundred forty
      seven patients with a known 1q21 status were included in this study. The 347
      patients were divided into three groups, that is, 119 patients with the 1q21
      gain, 105 patients with other aberrations (OA), that is, del(13q), del(17p),
      t(4,14), and/or (14;16), and 123 patients with no aberrations (NA). The groups
      were compared in terms of overall survival (OS), time to progression (TTP), and
      response. The 3-yr OS for patients with gain 1q21 was 60% compared to patients
      with OA 74% and NO 82% (gain 1q21 vs. NO P < 0.001; gain 1q21 vs. OA P = 0.095).
      If treated with PI or IMiDs, the 3-yr OS was 58% for patients with gain 1q21
      compared to patients with OA 78% and NO 78%, respectively (P = 0.041, P = 0.140).
      In HDT patients, the 3-yr OS was 69% for patients with gain 1q21 compared to
      patients with OA 84% and NO 88%, respectively (P < 0.008, P = 0.600). Thus,
      neither HDT nor using PI or IMiDs could overcome the poor prognostic impact of
      gain 1q21, while these drugs and HDT seemed to improve OS in patients with OA,
      approaching the survival in NO. Further, gain 1q21 appears to be one of the most
      important poor prognostic chromosomal aberrations in multiple myeloma with
      current treatments. Trials using new drugs or allogeneic transplantation are
      warranted.

PMID- 25779479
TI  - Long-term in vivo electromechanical reshaping for auricular reconstruction in the
      New Zealand white rabbit model.
AB  - OBJECTIVES/HYPOTHESIS: To demonstrate the dosimetry effect of electromechanical
      reshaping (EMR) on cartilage shape change, structural integrity, cellular
      viability, and remodeling of grafts in an in vivo long-term animal model. STUDY
      DESIGN: Animal study. METHODS: A subperichondrial cartilaginous defect was
      created within the base of the pinna of 31 New Zealand white rabbits. Autologous
      costal cartilage grafts were electromechanically reshaped to resemble the rabbit
      auricular base framework and mechanically secured into the pinna base defect.
      Forty-nine costal cartilage specimens (four control and 45 experimental)
      successfully underwent EMR using a paired set of voltage-time combinations and
      survived for 6 or 12 weeks. Shape change was measured, and specimens were
      analyzed using digital imaging, tissue histology, and confocal microscopy with
      LIVE-DEAD viability assays. RESULTS: Shape change was proportional to charge
      transfer in all experimental specimens (P < .01) and increased with voltage. All
      experimental specimens contoured to the auricular base. Focal cartilage
      degeneration and fibrosis was observed where needle electrodes were inserted,
      ranging from 2.2 to 3.9 mm. The response to injury increased with increasing
      charge transfer and survival duration. CONCLUSIONS: EMR results in appropriate
      shape change in cartilage grafts with chondrocyte injury highly localized. These
      studies suggest that elements of auricular reconstruction may be feasible using
      EMR. Extended survival periods and further optimization of voltage-time pairs are
      necessary to evaluate the long-term effects and shape-change potential of EMR.
      LEVELS OF EVIDENCE: NA.

PMID- 25779480
TI  - Synthesis and Photophysics of BF2 -Rigidified Partially Closed Chain
      Bromotetrapyrroles: Near Infrared Emitters and Photosensitizers.
AB  - We report the synthesis, crystallographic, optical, and triplet and singlet
      oxygen generation properties of a series of BF2 -rigidified partially closed
      chain bromotetrapyrroles as near infrared emitters and photosensitizers. These
      novel dyes were efficiently synthesized from a nucleophilic substitution reaction
      between pyrroles and the 3,5-bromo-substituents on the tetra- and
      hexabromoBODIPYs and absorb in the near-infrared region (681-754 nm) with high
      molar extinction coefficients. Their fluorescent emission (708-818 nm) and
      singlet oxygen generation properties are significantly affected by alkyl
      substitutions on the two uncoordinated pyrrole units of these dyes and the
      polarity of solvents. Among them, dyes 4 ca and 4 da show good singlet oxygen
      generation efficiency and good NIR fluorescence emission (fluorescence quantum
      yields of 0.14-0.43 in different solvents studied).

PMID- 25779481
TI  - Isoniazid poisoning: Pharmacokinetics and effect of hemodialysis in a massive
      ingestion.
AB  - Isoniazid is a rare overdose that causes seizures and there is limited evidence
      to guide treatment. We report a 20-year-old female migrant who presented with
      recurrent seizures after ingesting 25 g of isoniazid. She was treated with
      activated charcoal, repeated doses of midazolam for the seizures, and given
      multiple doses of pyridoxine (14 mg), limited by availability. She was admitted
      to intensive care, and 5.5 hours post-ingestion, she was commenced on continuous
      veno-venous hemodiafiltration (CVVHDF). She was extubated after 24 hours and
      CVVHDF was ceased 6 hours later (30 hours post-overdose). Her renal function
      remained normal and her initial lactate was the highest at 2.3. She made a full
      recovery. Five plasma samples were collected before, during, and after CVVHDF,
      and isoniazid was quantified with liquid chromatography-tandem mass spectrometry.
      A pharmacokinetic analysis of time-isoniazid concentration data was fitted to a
      two-compartment model with first-order input (with fixed ka ) with the effect of
      CVVHDF modeled as a time-dependent covariate. This suggested that there was
      initially good clearance with CVVHDF (4 times endogenous clearance), which
      rapidly declined within hours. 

PMID- 25779482
TI  - Arabidopsis cytosolic acyl-CoA-binding proteins ACBP4, ACBP5 and ACBP6 have
      overlapping but distinct roles in seed development.

PMID- 25779483
TI  - Inheritance of photoperiodic control of larval diapause in the Asian corn borer
      Ostrinia furnacalis (Guenee).
AB  - The Asian corn borer, Ostrinia furnacalis enters diapause as fully grown larvae.
      Owing to geographical variation in photoperiodic control of diapause, the
      subtropical strain from Hefei city (HF) enters diapause in response to short
      daylengths, whereas the tropical strain from Ledong county (LD) exhibits almost
      no diapause under the same conditions. The two strains were used in crosses to
      study the inheritance of diapause. The HF strain showed a typical long-day
      response with a critical daylength of approximately 14.97 h at 22  degrees C,
      14.60 h at 25  degrees C and 13.68 h at 28  degrees C. The LD strain showed weak
      photoperiodic responses at 22 and 25  degrees C; and the F1 progeny also showed a
      long-day response with significantly shorter critical daylength compared with the
      HF strain. However, the LD * HF (F * M) crosses had significantly longer critical
      daylengths than HF * LD crosses, indicating a sexual bias in the inheritance of
      diapause induction, with the male parent having more influence on the F1 progeny.
      The critical daylength in a backcross to HF was significantly longer than a
      backcross to LD. Whether the inheritance of diapause fits an additive hypothesis
      or not depended on photoperiod, with results from different photoperiods showing
      additive inheritance or incomplete dominance of either diapause or non-diapause.
      Unlike diapause induction, the duration of diapause for reciprocal crosses was
      equally influenced by each parent, suggesting that diapause incidence and
      maintenance are controlled by separate systems in O. furnacalis.

PMID- 25779511
TI  - Smart scaffolds: the future of bioceramic.
AB  - The commercial offer for bioceramic bone substitutes is very large, however, the
      prerequisites for applications in bone reconstruction and tissue engineering, are
      most often absent. The main criteria being: on the one hand physico-chemical
      features providing surgeons with an injectable and/or shapeable biomaterial; on
      the second hand the multi-scale bioactivity leading to osteoconduction and
      osteoinduction properties. In order to obtain greater suitability according to
      the nature of the bone defect to be treated, new bone regeneration technologies,
      "smart scaffolds" must be developed and optimize to support suitable Ortho
      Biology. 

PMID- 25779512
TI  - Inflammatory cytokine release is affected by surface morphology and chemistry of
      titanium implants.
AB  - To investigate in vitro cellular cytokine expression in relation to commercially
      pure titanium discs, comparing a native surface to a fluorinated oxide nanotube
      surface. Control samples pure titanium discs with a homogenous wave of the
      margins and grooves and an often smeared-out surface structure. Test samples pure
      titanium discs with a fluorinated titanium oxide chemistry and surface morphology
      with nanopore/tube geometry characterized by ordered structures of nanotubes with
      a diameter of ~ 120 nm, a spacing of ~ 30 nm, and a wall thickness of ~ 10 nm.
      Cross-section view showed vertically aligned nanotubes with similar lengths of ~
      700 nm. Peripheral blood mononuclear leucocytes were cultured for 1, 3, and 6
      days according to standard procedures. BioPlex ProTM assays were used for
      analysis and detection of cytokines. Selected inflammatory cytokines are
      reported. A pronounced difference in production of the inflammatogenic cytokines
      was observed. Leucocytes exposed to control coins produced significantly more TNF
      alpha, IL-1beta, and IL-6 than the test nanotube coins. The effect on the TH2
      cytokine IL-4 was less pronounced at day 6 compared to days 1 and 3, and slightly
      higher expressed on the control coins. The morphology and surface chemistry of
      the titanium surface have a profound impact on basic cytokine production in
      vitro. Within the limitations of the present study, it seems that the fluorinated
      oxide nanotube surface results in a lower inflammatory response compared to a
      rather flat surface that seems to favour inflammation.

PMID- 25779514
TI  - Vets can call themselves Dr - RCVS.

PMID- 25779513
TI  - Biofabricated constructs as tissue models: a short review.
AB  - Biofabrication is currently able to provide reliable models for studying the
      development of cells and tissues into multiple environments. As the complexity of
      biofabricated constructs is becoming increasingly higher their ability to closely
      mimic native tissues and organs is also increasing. Various biofabrication
      technologies currently allow to precisely build cell/tissue constructs at
      multiple dimension ranges with great accuracy. Such technologies are also able to
      assemble together multiple types of cells and/or materials and generate
      constructs closely mimicking various types of tissues. Furthermore, the high
      degree of automation involved in these technologies enables the study of large
      arrays of testing conditions within increasingly smaller and automated devices
      both in vitro and in vivo. Despite not yet being able to generate constructs
      similar to complex tissues and organs, biofabrication is rapidly evolving in that
      direction. One major hurdle to be overcome in order for such level of complex
      detail to be achieved is the ability to generate complex vascular structures
      within biofabricated constructs. This review describes several of the most
      relevant technologies and methodologies currently utilized within biofabrication
      and provides as well a brief overview of their current and future potential
      applications. 

PMID- 25779515
TI  - Royal Charter celebrated.

PMID- 25779516
TI  - Truly international turnout at this year's Crufts.

PMID- 25779517
TI  - Vets' priorities for happy, healthy dogs.

PMID- 25779518
TI  - Microchipping of dogs to be made compulsory in Scotland.

PMID- 25779519
TI  - Loan repaid.

PMID- 25779520
TI  - Transatlantic funding programme supports animal health research.

PMID- 25779521
TI  - Guidance for working safely on farms.

PMID- 25779523
TI  - Speaking up for cats: feline charity launches its manifesto.

PMID- 25779524
TI  - Call for action on puppy smuggling.
AB  - Georgina Mills reports from a breakfast briefing organised by the Dogs Trust at
      the House of Commons last month. The charity convened the briefing to discuss its
      recently published report into the illegal importation of puppies into the UK. 

PMID- 25779525
TI  - Spotlight on medical alert assistance dogs.

PMID- 25779526
TI  - Cattle veterinary services in a changing world.
AB  - In the first of a series of feature articles in Veterinary Record discussing the
      state of different sectors of the veterinary profession in the UK and what the
      future might hold, Jonathan Statham and Martin Green give their perspective on
      developments affecting the provision of cattle veterinary services. 

PMID- 25779527
TI  - Goats, lameness and treponemes - time for preventive measures?

PMID- 25779528
TI  - Food assurance scheme.

PMID- 25779529
TI  - Developing objective measures of gait abnormalities in dogs with degenerative
      myelopathy.

PMID- 25779530
TI  - Bridging the gap between school and university.
AB  - Emily Stacey is a third-year student at the Royal Veterinary College, and is one
      of a group of students that has developed an online course to help new students
      familiarise themselves with the topics they will study and the most useful ways
      to study them. 

PMID- 25779531
TI  - First-year student diary.
AB  - First-year Liverpool vet student Rosie Perrett finds that standard-issue surgical
      gowns are too long when you're not quite 5 feet tall. 

PMID- 25779532
TI  - Involvement of iron depletion in palmitate-induced lipotoxicity of beta cells.
AB  - High levels of plasma free fatty acid are thought to contribute to the loss of
      pancreatic beta-cells in type 2 diabetes. In particular, saturated fatty acid
      such as palmitate or stearate can induce apoptosis in cultured beta cells
      (lipotoxicity). Endoplasmic reticulum stress is a critical mediator of free fatty
      acid-induced lipotoxicity. Recently, disorders in mitochondrial respiratory
      metabolism have been linked to lipotoxicity. Since iron is a critical component
      of respiratory metabolism, this study is initiated to determine whether abnormal
      iron metabolism is involved in palmitate-induced beta cell death. Immunoblotting
      analysis showed that treatment of INS-1 beta cells with palmitate reduced the
      level of transferrin receptor 1 (TfR1), but increased the level of heavy chain
      ferritin (FTH). In addition, palmitate reduced intracellular labile iron pool.
      Whereas iron depletion through treatment with iron-chelators deferoxamine or
      deferasirox augmented palmitate-induced cell death, iron supplementation with
      ferric chloride, ferrous sulfate, or holo-transferrin significantly protected
      cells against palmitate-induced death. Furthermore, overexpression of TfR1
      reduced palmitate-induced cell death, whereas knockdown of TfR1 augmented cell
      death. In particular, treatment with deferoxamine increased the level of
      endoplasmic reticulum (ER) stress markers phospho-PERK, phospho-eIF2alpha, CHOP
      and phospho-c-Jun N-terminal kinase. Treatment with chemical chaperone
      significantly protected cells against deferoxamine-induced apoptosis. Iron
      supplementation also protected cells against palmitate-induced primary islet
      death. These data suggest that iron depletion plays an important role in
      palmitate-induced beta cell death through inducing ER stress. Therefore, attempts
      to block iron depletion might be able to prevent beta cell loss in type 2
      diabetes. 

PMID- 25779533
TI  - Caloric restriction and the adipokine leptin alter the SDF-1 signaling axis in
      bone marrow and in bone marrow derived mesenchymal stem cells.
AB  - Growing evidence suggests that the chemokine stromal cell-derived factor-1 (SDF
      1) is essential in regulating bone marrow (BM) derived mesenchymal stromal/stem
      cell (BMSC) survival, and differentiation to either a pro-osteogenic or pro
      adipogenic fate. This study investigates the effects of caloric restriction (CR)
      and leptin on the SDF-1/CXCR4 axis in bone and BM tissues in the context of age
      associated bone loss. For in vivo studies, we collected bone, BM cells and BM
      interstitial fluid from 12 and 20 month-old C57Bl6 mice fed ad-libitum (AL), and
      20-month-old mice on long-term CR with, or without, intraperitoneal injection of
      leptin for 10 days (10 mg/kg). To mimic conditions of CR in vitro, 18 month
      murine BMSCs were treated with (1) control (Ctrl): normal proliferation medium,
      (2) nutrient restriction (NR): low glucose, low serum medium, or (3) NR + leptin:
      NR medium + 100 ng/ml leptin for 6-48 h. In BMSCs both protein and mRNA
      expression of SDF-1 and CXCR4 were increased by CR and CR + leptin. In contrast,
      the alternate SDF-1 receptor CXCR7 was decreased, suggesting a nutrient signaling
      mediated change in SDF-1 axis signaling in BMSCs. However, in bone SDF-1, CXCR4
      and 7 gene expression increase with age and this is reversed with CR, while
      addition of leptin returns this to the "aged" level. Histologically bone
      formation was lower in the calorically restricted mice and BM adipogenesis
      increased, both effects were reversed with the 10 day leptin treatment. This
      suggests that in bone CR and leptin alter the nutrient signaling pathways in
      different ways to affect the local action of the osteogenic cytokine SDF-1.
      Studies focusing on the molecular interaction between nutrient signaling by CR,
      leptin and SDF-1 axis may help to address age-related musculoskeletal changes.

PMID- 25779534
TI  - Study on the mesothelin-specific cytotoxicity against epithelial ovarian cancer
      with full-length mesothelin cDNA-transduced dendritic cells.
AB  - Epithelial ovarian cancer (EOC) has the highest mortality rate among the various
      types of gynecological cancers. As the current therapeutic approaches are not
      enough, the development of more effective treatments to improve the survival of
      patients with EOC is urgently needed. Mesothelin (MSLN) is a cell surface
      glycoprotein, which is overexpressed in ovarian cancer tissues. As an
      immunotherapeutic approach, in this study, we investigated whether the
      genetically modified dendritic cells (DCs) expressing MSLN could induce cytotoxic
      T lymphocytes (CTLs) to produce MSLN-specific cytotoxic activity against EOCs.
      Here, we report that DCs transfected with full-length coding sequence of MSLN
      could induce MSLN-specific CTLs responses against ovarian cancer lines SKOV3 and
      OVCAR3 in vitro. Additionally, we identified that the death rates of ovarian
      cancer cells, killed by MSLN-specific CTLs, were significantly higher than the
      normal CTLs. Furthermore, IFN-gamma production by stimulated MSLN-specific CTLs
      was significantly higher than that of unstimulated CTLs. This study showed that
      induced CTLs by DCs with full-length MSLN cDNA have effective immune response
      against the ovarian cancer cells, indicating that MSLN-transfected DCs vaccine
      has a promising prospect for the treatment of EOC. 

PMID- 25779535
TI  - DLC-1 induces mitochondrial apoptosis and epithelial mesenchymal transition
      arrest in nasopharyngeal carcinoma by targeting EGFR/Akt/NF-kappaB pathway.
AB  - Loss of deleted in liver cancer-1 (DLC-1) can induce apoptosis and inhibit the
      mobility, migration and metastasis in several cancers. Previously, we revealed
      that ectopic expression of DLC-1 can suppress proliferation, mobility, migration
      and tumorigenesis in nasopharyngeal carcinoma (NPC). However, the molecular
      mechanisms accounting for the roles of DLC-1 in NPC are still obscure. In the
      present work, we attempted to study and uncover the mechanisms underlying the
      functions of DLC-1 in NPC. The apoptosis of 5-8F-DLC-1 cells, established
      previously, was analyzed by mitochondrial membrane potentials assay and flow
      cytometer analysis. And the antibodies involving pathways such as mitochondrial
      associated apoptosis, epithelial mesenchymal transition and metastasis were
      applied to detect and compare the expression level of targeted proteins. The
      obvious apoptosis of 5-8F-DLC-1 cells was observed reflected by mitochondrial
      depolarization and lower ratio in cell viability. Subsequently, the activation of
      mitochondrial apoptosis was verified by the increased expressions of Bax, Apaf1,
      cleave-caspases and cleave-PARP, etc, and the decreased expressions of Bcl-2, Bcl
      xL, Mcl-1, Survivin, etc, in 5-8F-DLC-1 cells. Then, the inhibited epithelial
      mesenchymal transition of 5-8F-DLC-1 cells was validated by upregulated
      expression of E-cadherin and downregulated expression of N-cadherin, Snail,
      Vimentin. Subsequently, downregulated expressions of proteins such as FAK, RhoA,
      ROCK1 and cdc25 related to cell adhesion and cytoskeleton organization were also
      observed. And expressions of MMPs were inhibited in 5-8F-DLC-1 cells. At last,
      the inhibited activity of EGFR/Akt/NF-kappaB axis was revealed by the decreased
      expressions of phosho-EGFR, phosho-Akt, phosho-p38MAPK, phosho-IKKalpha and
      phosho-p65. Here, we systematically explored the mechanisms underlying the
      negative roles of DLC-1 in NPC cells. For the first time, we confirmed that the
      ectopic expression DLC-1 can induce mitochondrial apoptosis, inhibit EMT and
      related processes by targeting the EGFR/Akt/NF-kappaB pathway, which, beyond all
      doubt, offered beneficial guidelines for other studies and laid a good foundation
      for its clinical applications ultimately. 

PMID- 25779536
TI  - Analytical methodologies for the determination of benzodiazepines in biological
      samples.
AB  - Benzodiazepine drugs belong to important and most widely used medicaments. They
      demonstrate such therapeutic properties as anxiolytic, sedative, somnifacient,
      anticonvulsant, diastolic and muscle relaxant effects. However, despite the fact
      that benzodiazepines possess high therapeutic index and are considered to be
      relatively safe, their use can be dangerous when: (1) co-administered with
      alcohol, (2) co-administered with other medicaments like sedatives,
      antidepressants, neuroleptics or morphine like substances, (3) driving under
      their influence, (4) using benzodiazepines non-therapeutically as drugs of abuse
      or in drug-facilitated crimes. For these reasons benzodiazepines are still
      studied and determined in a variety of biological materials. In this article,
      sample preparation techniques which have been applied in analysis of
      benzodiazepine drugs in biological samples have been reviewed and presented. The
      next part of the article is focused on a review of analytical methods which have
      been employed for pharmacological, toxicological or forensic study of this group
      of drugs in the biological matrices. The review was preceded by a description of
      the physicochemical properties of the selected benzodiazepines and two, very
      often coexisting in the same analyzed samples, sedative-hypnotic drugs. 

PMID- 25779537
TI  - Prognostic value of vascular endothelial growth factor and hypoxia-inducible
      factor 1alpha in canine malignant mammary tumors.
AB  - Mammary tumors are the most common type of tumor in dogs, with approximately half
      of these tumors being malignant. Hypoxia, characterized by oxygen levels below
      normal, is a known adverse factor to cancer treatment. The hypoxia-inducible
      factor 1alpha (HIF-1alpha) is a central regulator of the pathophysiological
      response of mammalian cells to low oxygen levels. HIF-1alpha activates the
      transcription of vascular endothelial growth factor (VEGF), which in turn
      promotes angiogenesis through its ability to stimulate the growth, migration and
      invasion of endothelial cells to form new blood vessels, contributing to tumor
      progression. In this study, we evaluated the serum concentration and gene
      expression of VEGF and HIF-1alpha linking them with clinicopathological
      parameters and survival of dogs with mammary tumors in order to infer the
      possible prognostic value of these factors. We collected blood and tumor
      fragments of 24 female dogs with malignant mammary tumors (study group) and 26
      non-affected female dogs (control group) to verify the gene expression of VEGF
      and HIF-1alpha by quantitative real-time PCR (qPCR) and the serum levels by ELISA
      (enzyme-linked immunosorbent). The results showed high serum levels of VEGF in
      the study group and its correlation between abundant vascularization, lymph node
      involvement, metastasis, death rate and low survival (p<0.05). The serum
      percentage of HIF-1alpha in female dogs with mammary neoplasia was lower than
      that in the control group and higher in female dogs with tumor metastasis and
      history of tumor recurrence (p<0.05). Regarding gene expression, there was a gene
      overexpression of VEGFA in female dogs with poor outcome, in contrast to the gene
      underexpression of HIF-1A. Taken together, these results suggested that VEGF is
      important in tumor progression and can be used as a potential prognostic marker
      in the clinic and may be useful in predicting tumor progression in dogs with
      mammary neoplasia. 

PMID- 25779539
TI  - About the article: Prevalence of lower urinary tract symptoms in individuals with
      Down syndrome.

PMID- 25779538
TI  - How should children with West syndrome be efficiently and accurately
      investigated? Results from the National Infantile Spasms Consortium.
AB  - OBJECTIVE: To prospectively evaluate the etiology of new-onset infantile spasms
      and evaluate the yield of genetic and metabolic investigations in those without
      obvious cause after initial clinical evaluation and magnetic resonance imaging
      (MRI). METHODS: Twenty-one U.S. pediatric epilepsy centers prospectively enrolled
      infants with newly diagnosed West syndrome in a central database. Etiology and
      investigations performed within 3 months of diagnosis were documented. RESULTS:
      From June 2012 to June 2014, a total of 251 infants were enrolled (53% male). A
      cause was identified in 161 (64.4%) of 250 cases (genetic,14.4%; genetic
      structural, 10.0%; structural-congenital, 10.8%; structural-acquired, 22.4%;
      metabolic, 4.8%; and infectious, 2.0%). An obvious cause was found after initial
      clinical assessment (history and physical examination) and/or MRI in 138 of 161,
      whereas further genetic and metabolic studies were revealing in another 23 cases.
      Of 112 subjects without an obvious cause after initial evaluation and MRI, 81
      (72.3%) had undergone genetic testing, which showed a causal abnormality in 23.5%
      and a variant of unknown significance in 14.8%. Although metabolic studies were
      done in the majority (serum, 79.5%; urine, 69.6%; and cerebrospinal fluid [CSF],
      38.4%), these revealed an etiology in only five cases (4.5%). No correlation was
      found between type of health insurance (public vs. private) and either genetic or
      metabolic testing. SIGNIFICANCE: Clinical evaluation and MRI provide a specific
      diagnosis in 55% of children presenting with West syndrome. We propose that a
      cost-effective workup for those without obvious cause after initial clinical
      evaluation and MRI includes an array comparative genomic hybridization (aCGH)
      followed by an epilepsy gene panel if the microarray is not definitive, serum
      lactate, serum amino acids, and urine organic acids.

PMID- 25779540
TI  - Interobserver agreement in retrospective chart reviews for factors associated
      with cervical spine injuries in children.
AB  - OBJECTIVES: The objective was to describe the interobserver agreement between
      trained chart reviewers and physician reviewers in a multicenter retrospective
      chart review study of children with cervical spine injuries (CSIs). METHODS:
      Medical records of children younger than 16 years old with cervical spine
      radiography from 17 Pediatric Emergency Care Applied Research Network (PECARN)
      hospitals from years 2000 through 2004 were abstracted by trained reviewers for a
      study aimed to identify predictors of CSIs in children. Independent physician
      reviewers abstracted patient history and clinical findings from a random sample
      of study patient medical records at each hospital. Interobserver agreement was
      assessed using percent agreement and the weighted kappa (kappa) statistic, with
      lower 95% confidence intervals. RESULTS: Moderate or better agreement (kappa >
      0.4) was achieved for most candidate CSI predictors, including altered mental
      status (kappa = 0.87); focal neurologic findings (kappa = 0.74); posterior
      midline neck tenderness (kappa = 0.74); any neck tenderness (kappa = 0.89);
      torticollis (kappa = 0.79); complaint of neck pain (kappa = 0.83); history of
      loss of consciousness (kappa = 0.89); nonambulatory status (kappa = 0.74); and
      substantial injuries to the head (kappa = 0.50), torso/trunk (kappa = 0.48), and
      extremities (kappa = 0.59). High-risk mechanisms showed near-perfect agreement
      (diving, kappa = 1.0; struck by car, kappa = 0.93; other motorized vehicle crash,
      kappa = 0.93; fall, kappa = 0.92; high-risk motor vehicle collision, kappa =
      0.89; hanging, kappa = 0.80). Fair agreement was found for clotheslining
      mechanisms (kappa = 0.36) and substantial face injuries (kappa = 0.40).
      CONCLUSIONS: Most retrospectively assessed variables thought to be predictive of
      CSIs in blunt trauma-injured children had at least moderate interobserver
      agreement, suggesting that these data are sufficiently valid for use in
      identifying potential predictors of CSI.

PMID- 25779541
TI  - Temporal trends in the incidence and prognosis of aortic stenosis: a nationwide
      study of the Swedish population.
AB  - BACKGROUND: The aging of Western populations is expected to result in increasing
      occurrence of aortic stenosis (AS), but data are limited. Recent studies have
      reported declining incidence and mortality for other major heart diseases. We
      aimed to study temporal trends in the incidence and prognosis for AS in Sweden.
      METHODS AND RESULTS: With the use of nationwide registers, all adult patients in
      the Swedish population with a first diagnosis of AS, heart failure, acute
      myocardial infarction, and aortic valve replacement for AS between 1989 and 2009
      were identified and followed up until the end of 2010 for all-cause and
      cardiovascular-related mortality. The age-adjusted incidence of AS in Sweden
      declined from 15.0 to 11.4 in men and 9.8 to 7.1 in women per 100 000 between
      1989 to 1991 and 2007 to 2009, and the median age at diagnosis increased by 4
      years for both men and women. The age- and sex-adjusted relative risk of 1- and 3
      year mortality in 2007 to 2009 was 0.58 (95% confidence interval, 0.53-0.63) and
      0.60 (95% confidence interval, 0.56-0.65), respectively, compared with 1989 to
      1991. Similar improvements were observed for heart failure and acute myocardial
      infarction. Findings were broadly consistent across subgroups. Postoperative
      mortality at 30 days declined despite increased median age at diagnosis.
      CONCLUSIONS: Incidence and mortality rates in AS in Sweden declined between 1989
      and 2009 to an extent similar to that observed for heart failure and acute
      myocardial infarction. These findings could suggest that improved risk factor
      control and cardiovascular therapy, combined with increased use of aortic valve
      replacement in the elderly and reduced perioperative mortality in aortic valve
      replacement, have translated into favorable effects for AS.

PMID- 25779543
TI  - Echo-Doppler hemodynamics: an important management tool for today's heart failure
      care.

PMID- 25779545
TI  - Impact of ascending to descending aortic bypass for aortic coarctation on 3
      dimensional hemodynamics.

PMID- 25779542
TI  - Immune cell and other noncardiomyocyte regulation of cardiac hypertrophy and
      remodeling.

PMID- 25779546
TI  - Myocardial bridging in a man with non-ST-elevation myocardial infarction.

PMID- 25779547
TI  - Letter by Galyfos and Filis regarding article, "effects of sex on coronary
      microvascular dysfunction and cardiac outcomes".

PMID- 25779548
TI  - Response to letter regarding article, "effects of sex on coronary microvascular
      dysfunction and cardiac outcomes".

PMID- 25779549
TI  - Letter by Durukan regarding article, "surgical revascularization is associated
      with maximal survival in patients with ischemic mitral regurgitation: a 20-year
      experience".

PMID- 25779550
TI  - Response to letter regarding article, "surgical revascularization is associated
      with maximal survival in patients with ischemic mitral regurgitation: a 20-year
      experience".

PMID- 25779551
TI  - Systemic methotrexate for the treatment of psoriasis.
AB  - In the era of biologic therapies, methotrexate (MTX), a classic immunomodulator,
      is still the cornerstone of systemic treatment of psoriasis. MTX has been used
      for many years, achieving good responses with a good safety profile. However,
      only a few randomized clinical trials have been performed involving MTX, and most
      of the current evidence comes from pivotal studies of biologic drugs. The aim of
      this article is to make an extensive review of the MTX mechanism of action,
      pharmacokinetics, efficacy, safety and tolerability, especially focusing on the
      future perspective of this old drug and recent advances in the field of
      pharmacogenetics. 

PMID- 25779552
TI  - Association of Anti-Porphyromonas gingivalis Antibody Titers With Nonsmoking
      Status in Early Rheumatoid Arthritis: Results From the Prospective French Cohort
      of Patients With Early Rheumatoid Arthritis.
AB  - OBJECTIVE: To investigate the possible link between Porphyromonas gingivalis
      infection and rheumatoid arthritis (RA), according to antibody profile, genetic
      and environmental factors, and RA severity. METHODS: For assessing P gingivalis
      infection, serum levels of antibodies directed against P gingivalis
      lipopolysaccharide were measured in 694 patients with early RA who were not
      exposed to steroids or disease-modifying antirheumatic drugs. Anti-P gingivalis
      antibody titers were compared between patients with early RA and various control
      groups, and according to various patient characteristics. RESULTS: Anti-P
      gingivalis antibody titers did not significantly differ between patients with RA
      and controls and did not significantly differ with anti-citrullinated protein
      antibody (ACPA), rheumatoid factor (RF), or HLA shared epitope status. Anti-P
      gingivalis antibody titers were significantly higher among patients who had never
      smoked compared to patients who had ever smoked (P = 0.0049). Among nonsmokers,
      high anti-P gingivalis antibody levels were associated with a higher prevalence
      of erosive change (47.5% versus 33.3% with modified Sharp/van der Heijde score
      erosion subscale >=1; P = 0.0135). CONCLUSION: In this large early RA cohort, we
      did not detect any association of anti-P gingivalis antibodies with RA or with
      ACPA status. These results suggest that the association of periodontitis and RA
      could be linked to bacterial species other than P gingivalis or to a mechanism
      other than citrullination. Nevertheless, we found higher anti-P gingivalis
      antibody titers in nonsmokers. In addition, in this population of nonsmokers,
      high anti-P gingivalis antibody titers were associated with more severe disease.
      We hypothesize that the role of tobacco in RA pathogenesis is so high that the
      effect of P gingivalis could be revealed only in a population not exposed to
      tobacco.

PMID- 25779553
TI  - Cost-effective sampling of (137)Cs-derived net soil redistribution: part 2 -
      estimating the spatial mean change over time.
AB  - The caesium-137 ((137)Cs) technique for estimating net, time-integrated soil
      redistribution by the processes of wind, water and tillage is increasingly being
      used with repeated sampling to form a baseline to evaluate change over small
      (years to decades) timeframes. This interest stems from knowledge that since the
      1950s soil redistribution has responded dynamically to different phases of land
      use change and management. Currently, there is no standard approach to detect
      change in (137)Cs-derived net soil redistribution and thereby identify the
      driving forces responsible for change. We outline recent advances in space-time
      sampling in the soil monitoring literature which provide a rigorous statistical
      and pragmatic approach to estimating the change over time in the spatial mean of
      environmental properties. We apply the space-time sampling framework, estimate
      the minimum detectable change of net soil redistribution and consider the
      information content and cost implications of different sampling designs for a
      study area in the Chinese Loess Plateau. Three phases (1954-1996, 1954-2012 and
      1996-2012) of net soil erosion were detectable and attributed to well-documented
      historical change in land use and management practices in the study area and
      across the region. We recommend that the design for space-time sampling is
      considered carefully alongside cost-effective use of the spatial mean to detect
      and correctly attribute cause of change over time particularly across spatial
      scales of variation. 

PMID- 25779554
TI  - Patterns and predictors of sexual function after liver donation: The Adult-to
      Adult Living Donor Liver Transplantation Cohort study.
AB  - Although sexual functioning is an important facet of a living donor's quality of
      life, it has not received an extensive evaluation in this population. Using data
      from the Adult-to-Adult Living Donor Liver Transplantation Cohort Study, we
      examined donor sexual functioning across the donation process from the
      predonation evaluation to 3 months and 1 year after donation. Donors (n = 208)
      and a comparison group of nondonors (n = 155) completed self-reported surveys
      with specific questions on sexual desire, satisfaction, orgasm, and (for men)
      erectile function. Across the 3 time points, donor sexual functioning was lower
      at the evaluation phase and 3 months after donation versus 1 year after donation.
      In the early recovery period, abdominal pain was associated with difficulty
      reaching orgasm [odds ratio (OR), 3.98; 95% confidence interval (CI), 1.30
      12.16], concerns over appearance were associated with lower sexual desire (OR,
      4.14; 95% CI, 1.02-16.79), and not feeling back to normal was associated with
      dissatisfaction with sexual life (OR, 3.58; 95% CI, 1.43-8.99). Efforts to
      educate donors before the surgery and prepare them for the early recovery phase
      may improve recovery and reduce distress regarding sexual functioning.

PMID- 25779555
TI  - Pulmonary and circulatory parameter guided anesthesia in patients with ischemic
      stroke undergoing endovascular recanalization.
AB  - BACKGROUND AND PURPOSE: Endovascular recanalization in ischemic stroke is often
      performed under general anesthesia. Some studies have shown a detrimental effect
      of general anesthesia. The reasons are unknown. METHODS: This was an
      observational study with retrospective and prospective phases. From 2008 to 2010,
      60 patients treated by endovascular recanalization due to proximal vessel
      occlusion were analyzed with regard to ventilation parameters, blood gas values,
      blood pressure, and clinical parameters (pre-protocol phase). Subsequently, a
      protocol with target values for end-tidal CO2 (Petco2) and systolic blood
      pressure (SBP) was introduced and prospectively analyzed in 64 patients in 2012
      (protocol phase). RESULTS: In the pre-protocol phase, significant hypocapnia (<30
      mm Hg), a decrease in SBP after intervention (p<0.001), and an increase in SBP
      after extubation (p<0.001) were observed. After implementing the protocol in
      2012, 63% of Petco2 values and 55% of SBP values (median) of the duration of
      intervention were within the predefined range. Severe hypocapnia and hypotension
      (SBP <100 mm Hg) after the intervention were significantly reduced. Longer
      duration of Petco2 values within 40-45 mm Hg, intracerebral hemorrhage, longer
      door to needle time, older age, unsuccessful recanalization, longer duration of
      endovascular treatment, and higher cumulative dose of norepinephrine were
      associated with an unfavorable outcome (modified Rankin Scale score >2).
      Intracerebral hemorrhage (OR 0.028, p=0.001), age (OR 0.9, p=0.013), and
      cumulative dose of norepinephrine (OR 0.142, p=0.003) were independent predictors
      of an unfavorable outcome. CONCLUSIONS: In patients receiving endovascular stroke
      treatment under general anesthesia, the cumulative dose of norepinephrine was an
      independent predictor of an unfavorable outcome. Further studies are needed to
      evaluate the optimal management of blood pressure in these patients, and whether
      avoidance of catecholamines could partly explain the improved outcomes for
      patients treated under conscious sedation in retrospective studies.

PMID- 25779556
TI  - The feasibility of testing whether Fasciola hepatica is associated with increased
      risk of verocytotoxin producing Escherichia coli O157 from an existing study
      protocol.
AB  - The parasite Fasciola hepatica is a major cause of economic loss to the
      agricultural community worldwide as a result of morbidity and mortality in
      livestock, including cattle. Cattle are the principle reservoir of
      verocytotoxigenic Escherichia coli O157 (VTEC O157), an important cause of
      disease in humans. To date there has been little empirical research on the
      interaction between F. hepatica and VTEC O157. It is hypothesised that F.
      hepatica, which is known to suppress type 1 immune responses and induce an anti
      inflammatory or regulatory immune environment in the host, may promote
      colonisation of the bovine intestine with VTEC O157. Here we assess whether it is
      statistically feasible to augment a prospective study to quantify the prevalence
      of VTEC O157 in cattle in Great Britain with a pilot study to test this
      hypothesis. We simulate data under the framework of a mixed-effects logistic
      regression model in order to calculate the power to detect an association effect
      size (odds ratio) of 2. In order to reduce the resources required for such a
      study, we exploit the fact that the test results for VTEC O157 will be known in
      advance of testing for F. hepatica by restricting analysis to farms with a VTEC
      O157 sample prevalence of >0% and <100%. From a total of 270 farms (mean 27 cows
      per farm) that will be tested for VTEC O157, power of 87% can be achieved,
      whereby testing of F. hepatica would only be necessary for an expected 50 farms,
      thus considerably reducing costs. Pre-study sample size calculations are an
      important part of any study design. The framework developed here is applicable to
      the study of other co-infections. 

PMID- 25779557
TI  - Discussion about the prevalence of mental disorders depending on the different
      phases of cancer care within the cancer continuum.

PMID- 25779558
TI  - Lapatinib or Trastuzumab Plus Taxane Therapy for Human Epidermal Growth Factor
      Receptor 2-Positive Advanced Breast Cancer: Final Results of NCIC CTG MA.31.
AB  - PURPOSE: The efficacy of lapatinib versus trastuzumab combined with taxanes in
      the first-line setting of human epidermal growth factor receptor 2 (HER2) 
      positive metastatic breast cancer (BC) is unknown. PATIENTS AND METHODS: The
      MA.31 trial compared a combination of first-line anti-HER2 therapy (lapatinib or
      trastuzumab) and taxane therapy for 24 weeks, followed by the same anti-HER2
      monotherapy until progression. Stratification was by prior (neo)adjuvant anti
      HER2 therapy, prior (neo)adjuvant taxane, planned taxane, and liver metastases.
      The primary end point was intention-to-treat (ITT) progression-free survival
      (PFS), defined as time from random assignment to progression by RECIST (version
      1.0) criteria, or death for patients with locally assessed HER2-positive tumors.
      The primary test statistic was a stratified log-rank test for noninferiority. PFS
      was also assessed for patients with centrally confirmed HER2-positive tumors.
      RESULTS: From July 17, 2008, to December 1, 2011, 652 patients were accrued from
      21 countries, resulting in 537 patients with centrally confirmed HER2-positive
      tumors. Median follow-up was 21.5 months. Median ITT PFS was 9.0 months with
      lapatinib and 11.3 months with trastuzumab. By ITT analysis, PFS was inferior for
      lapatinib compared with trastuzumab, with a stratified hazard ratio (HR) of 1.37
      (95% CI, 1.13 to 1.65; P = .001). In patients with centrally confirmed HER2
      positive tumors, median PFS was 9.1 months with lapatinib and 13.6 months with
      trastuzumab (HR, 1.48; 95% CI, 1.20 to 1.83; P < .001). More grade 3 or 4
      diarrhea and rash were observed with lapatinib (P < .001). PFS results were
      supported by the secondary end point of overall survival, with an ITT HR of 1.28
      (95% CI, 0.95 to 1.72; P = .11); in patients with centrally confirmed HER2
      positive tumors, the HR was 1.47 (95% CI, 1.03 to 2.09; P = .03). CONCLUSION: As
      first-line therapy for HER2-positive metastatic BC, lapatinib combined with
      taxane was associated with shorter PFS and more toxicity compared with
      trastuzumab combined with taxane.

PMID- 25779559
TI  - Translocation t(11;14) is associated with adverse outcome in patients with newly
      diagnosed AL amyloidosis when treated with bortezomib-based regimens.
AB  - PURPOSE: Bortezomib has become a cornerstone in the treatment of AL amyloidosis.
      In this study, we addressed the prognostic impact of cytogenetic aberrations for
      bortezomib-treated patients. PATIENTS AND METHODS: We analyzed a consecutive
      series of 101 patients with AL amyloidosis treated with bortezomib-dexamethasone
      as first-line treatment by interphase fluorescence in situ hybridization (iFISH).
      Patients were ineligible for high-dose chemotherapy, which would put them at risk
      for cardiac or renal failure, and thus represented a poor-risk group. RESULTS:
      Presence of t(11;14), versus its absence, was associated with inferior
      hematologic event-free survival (median, 3.4 v 8.8 months, respectively; P =
      .002), overall survival (median, 8.7 v 40.7 months, respectively; P = .05), and
      remission rate (>= very good partial remission; 23% v 47%, respectively; P =
      .02). In multivariable Cox regression models incorporating established
      hematologic and clinical risk factors, t(11;14) was an independent adverse
      prognostic marker for hematologic event-free survival (hazard ratio, 2.94; 95%
      CI, 1.37 to 6.25; P = .006) and overall survival (hazard ratio, 3.13; 95% CI,
      1.16 to 8.33; P = .03), but not for remission (>= very good partial remission).
      Markedly, the multiple myeloma high-risk iFISH aberrations t(4;14), t(14;16),
      del(17p), and gain of 1q21 conferred no adverse prognosis in this bortezomib
      dexamethasone-treated group. After backward variable selection, the final
      multivariable model was validated in a consecutive series of 32 patients treated
      with bortezomib, dexamethasone, and cyclophosphamide. CONCLUSION: iFISH results
      are important independent prognostic factors in AL amyloidosis. In contrast to
      our recently published results with melphalan and dexamethasone standard therapy,
      bortezomib is less beneficial to patients harboring t(11;14), whereas it
      effectively alleviates the poor prognosis inherent to high-risk aberrations.
      Given the discrepant response to different treatment modalities, iFISH may help
      to guide therapeutic choices in these poor-risk patients requiring rapid
      hematologic response.

PMID- 25779560
TI  - Reply to C.e. Paiva et Al.

PMID- 25779561
TI  - Right to try?

PMID- 25779562
TI  - Increased incidence of fractures in recipients of hematopoietic stem-cell
      transplantation.
AB  - PURPOSE: The number of long-term survivors after hematopoietic stem-cell
      transplantation (HSCT) for malignant and nonmalignant disorders is increasing,
      and late effects are gaining importance. Osteoporosis and fractures can worsen
      the quality of life of HSCT survivors, but the burden of the disease is unknown.
      PATIENTS AND METHODS: We conducted a retrospective study of patients older than
      age 18 years who underwent an HSCT at The University of Texas MD Anderson Cancer
      Center from January 1, 1997, to December 31, 2011, and were observed until
      December 31, 2013, to ascertain occurrence of fractures. Cumulative incidence
      rates of fractures were calculated with death as a competing risk. Age- and sex
      specific incidence rates per person-year of fracture were compared with those of
      the US general population by using estimated rates from the 1994 National Health
      Interview Survey and the 2004 National Hospital Discharge Survey. RESULTS: A
      total of 7,620 patients underwent an HSCT from 1997 to 2011 at the MD Anderson
      Cancer Center of whom 602 (8%) developed a fracture. Age, underlying disease, and
      HSCT type were significantly associated with fracture. Age- and sex-specific
      fracture incidence rates after HSCT were significantly greater than those of the
      US general population in almost all subgroups. The striking difference was an
      approximately eight times greater risk in females and approximately seven to nine
      times greater risk in males age 45 to 64 years old when compared with the
      National Health Interview Survey and National Hospital Discharge Survey fracture
      rates. CONCLUSION: The incidence of fractures is compellingly higher after HSCT.

PMID- 25779564
TI  - Poly (ADP-ribose) polymerase inhibitors: recent advances and future development.
AB  - Poly (ADP-ribose) polymerase (PARP) inhibitors have shown promising activity in
      epithelial ovarian cancers, especially relapsed platinum-sensitive high-grade
      serous disease. Consistent with preclinical studies, ovarian cancers and a number
      of other solid tumor types occurring in patients with deleterious germline
      mutations in BRCA1 or BRCA2 seem to be particularly sensitive. However, it is
      also becoming clear that germline BRCA1/2 mutations are neither necessary nor
      sufficient for patients to derive benefit from PARP inhibitors. We provide an
      update on PARP inhibitor clinical development, describe recent advances in our
      understanding of PARP inhibitor mechanism of action, and discuss current issues
      in the development of these agents. 

PMID- 25779566
TI  - Antibody positron emission tomography imaging in anticancer drug development.
AB  - More than 50 monoclonal antibodies (mAbs), including several antibody-drug
      conjugates, are in advanced clinical development, forming an important part of
      the many molecularly targeted anticancer therapeutics currently in development.
      Drug development is a relatively slow and expensive process, limiting the number
      of drugs that can be brought into late-stage trials. Development decisions could
      benefit from quantitative biomarkers, enabling visualization of the tissue
      distribution of (potentially modified) therapeutic mAbs to confirm effective
      whole-body target expression, engagement, and modulation and to evaluate
      heterogeneity across lesions and patients. Such biomarkers may be realized with
      positron emission tomography imaging of radioactively labeled antibodies, a
      process called immunoPET. This approach could potentially increase the power and
      value of early trials by improving patient selection, optimizing dose and
      schedule, and rationalizing observed drug responses. In this review, we summarize
      the available literature and the status of clinical trials regarding the
      potential of immunoPET during early anticancer drug development. 

PMID- 25779565
TI  - C-reactive protein as a marker of melanoma progression.
AB  - PURPOSE: To investigate the association between blood levels of C-reactive
      protein (CRP) in patients with melanoma and overall survival (OS), melanoma
      specific survival (MSS), and disease-free survival. PATIENTS AND METHODS: Two
      independent sets of plasma samples from a total of 1,144 patients with melanoma
      (587 initial and 557 confirmatory) were available for CRP determination. Kaplan
      Meier method and Cox regression were used to evaluate the relationship between
      CRP and clinical outcome. Among 115 patients who underwent sequential blood
      draws, we evaluated the relationship between change in disease status and change
      in CRP using nonparametric tests. RESULTS: Elevated CRP level was associated with
      poorer OS and MSS in the initial, confirmatory, and combined data sets (combined
      data set: OS hazard ratio, 1.44 per unit increase of logarithmic CRP; 95% CI,
      1.30 to 1.59; P < .001; MSS hazard ratio, 1.51 per unit increase of logarithmic
      CRP; 95% CI, 1.36 to 1.68; P < .001). These findings persisted after
      multivariable adjustment. As compared with CRP < 10 mg/L, CRP >= 10 mg/L
      conferred poorer OS in patients with any-stage, stage I/II, or stage III/IV
      disease and poorer disease-free survival in those with stage I/II disease. In
      patients who underwent sequential evaluation of CRP, an association was
      identified between an increase in CRP and melanoma disease progression.
      CONCLUSION: CRP is an independent prognostic marker in patients with melanoma.
      CRP measurement should be considered for incorporation into prospective studies
      of outcome in patients with melanoma and clinical trials of systemic therapies
      for those with melanoma.

PMID- 25779568
TI  - Longitudinal study of extended-spectrum-beta-lactamase- and AmpC-producing
      Enterobacteriaceae in household dogs.
AB  - A longitudinal study was performed to (i) investigate the continuity of shedding
      of extended-spectrum-beta-lactamase (ESBL)-producing Enterobacteriaceae in dogs
      without clinical signs, (ii) identify dominant plasmid-mediated ESBL genes, and
      (iii) quantify ESBL-producing Enterobacteriaceae in feces. Fecal samples from 38
      dogs were collected monthly for 6 months. Additional samples were collected from
      7 included dogs on a weekly basis for 6 weeks. Numbers of CFU per gram of feces
      for non-wild-type Enterobacteriaceae were determined by using MacConkey agar
      supplemented with 1 mg/liter cefotaxime (MCC), and those for total
      Enterobacteriaceae were determined by using MacConkey agar. Cefotaxime-resistant
      isolates were screened by PCR and sequence analysis for the presence of bla(CTX
      M), bla(CMY), bla(SHV), bla(OXA), and bla(TEM) gene families. Bacterial species
      were identified by matrix-assisted laser desorption ionization-time of flight
      mass spectrometry (MALDI-TOF MS) analysis. PCR-negative isolates were tested by a
      double-disk synergy test for enhanced AmpC expression. A total of 259 samples
      were screened, and 126 samples were culture positive on MCC, resulting in 352
      isolates, 327 of which were Escherichia coli. Nine dogs were continuously
      positive during this study, and 6 dogs were continuously negative. Monthly or
      weekly shifts in fecal shedding were observed for 23 dogs. Genotyping showed a
      large variety of ESBL genes and gene combinations at single and multiple
      consecutive sampling moments. The ESBL genes bla(CTX-M-1), bla(CTX-M-14), bla(CTX
      M-15), bla(SHV-12), and bla(CMY-2) were most frequently found. The mean number of
      CFU of non-wild-type Enterobacteriaceae was 6.11 * 10(8) CFU/g feces. This study
      showed an abundance of ESBL-producing Enterobacteriaceae in dogs in the
      Netherlands, mostly in high concentrations. Fecal shedding was shown to be highly
      dynamic over time, which is important to consider when studying ESBL
      epidemiology.

PMID- 25779569
TI  - Tenofovir versus entecavir in treatment of chronic hepatitis B virus with severe
      acute exacerbation.
AB  - Tenofovir disoproxil fumarate (TDF) and entecavir (ETV) are effective antivirals
      recommended as first-line monotherapies for treatment of chronic hepatitis B
      (CHB) infection. This study aimed to compare the short-term efficacies of TDF and
      ETV in the treatment of CHB with severe acute exacerbation. From 2008 to 2013,
      189 consecutive treatment-naive CHB patients receiving TDF (n = 41) or ETV (n =
      148) for severe acute exacerbation were enrolled. The primary endpoint was
      overall mortality or receipt of liver transplantation by week 24. The baseline
      characteristics were comparable between these two groups. By week 24, 8 (19% [95%
      confidence interval {CI}, 7% to 32%]) patients in the TDF group and 26 (18% [95%
      CI, 11 to 24%]) patients in the ETV group died (n = 30) or received liver
      transplantation (n = 4) (P = 0.749). The two groups of patients developed similar
      rates of liver-related complications and achieved comparable biochemical and
      virological responses at week 24. Cox regression analysis showed that baseline
      viral DNA level (P = 0.002), hypertension (P = 0.002), model for end-stage liver
      disease (MELD) score (P = 0.01), platelet count (P = 0.005), early presence
      (within 4 weeks) of ascites (P = 0.005), hepatic encephalopathy (P = 0.002), and
      hepatorenal syndrome (P < 0.001) were independent factors for mortality or liver
      transplantation. Among the patients who survived by week 24, there was no
      difference between the two groups in the percentage of patients who had a serum
      creatinine increase of >=0.5 mg/dl from baseline (6.7% [95% CI, 0% to 16%] versus
      2.0% [95% CI, 0% to 4.8%] in the TDF and ETV groups, respectively; P = 0.231),
      whereas a significant reduction in the estimated glomerular filtration rate
      (eGFR) was found in the two groups (P = 0.001 for both). In conclusion, TDF and
      ETV produce a similar treatment response and clinical outcome in patients with
      severe acute exacerbation of CHB.

PMID- 25779570
TI  - Ceftriaxone-resistant Salmonella enterica serotype typhimurium sequence type 313
      from Kenyan patients is associated with the blaCTX-M-15 gene on a novel IncHI2
      plasmid.
AB  - Multidrug-resistant bacteria pose a major challenge to the clinical management of
      infections in resource-poor settings. Although nontyphoidal Salmonella (NTS)
      bacteria cause predominantly enteric self-limiting illness in developed
      countries, NTS is responsible for a huge burden of life-threatening bloodstream
      infections in sub-Saharan Africa. Here, we characterized nine S. Typhimurium
      isolates from an outbreak involving patients who initially failed to respond to
      ceftriaxone treatment at a referral hospital in Kenya. These Salmonella enterica
      serotype Typhimurium isolates were resistant to ampicillin, chloramphenicol,
      cefuroxime, ceftriaxone, aztreonam, cefepime, sulfamethoxazole-trimethoprim, and
      cefpodoxime. Resistance to beta-lactams, including to ceftriaxone, was associated
      with carriage of a combination of blaCTX-M-15, blaOXA-1, and blaTEM-1 genes. The
      genes encoding resistance to heavy-metal ions were borne on the novel IncHI2
      plasmid pKST313, which also carried a pair of class 1 integrons. All nine
      isolates formed a single clade within S. Typhimurium ST313, the major clone of an
      ongoing invasive NTS epidemic in the region. This emerging ceftriaxone-resistant
      clone may pose a major challenge in the management of invasive NTS in sub-Saharan
      Africa.

PMID- 25779571
TI  - Bactericidal monoclonal antibodies specific to the lipopolysaccharide O antigen
      from multidrug-resistant Escherichia coli clone ST131-O25b:H4 elicit protection
      in mice.
AB  - The Escherichia coli sequence type 131 (ST131)-O25b:H4 clone has spread worldwide
      and become responsible for a significant proportion of multidrug-resistant
      extraintestinal infections. We generated humanized monoclonal antibodies (MAbs)
      that target the lipopolysaccharide O25b antigen conserved within this lineage.
      These MAbs bound to the surface of live bacterial cells irrespective of the
      capsular type expressed. In a serum bactericidal assay in vitro, MAbs induced
      >95% bacterial killing in the presence of human serum as the complement source.
      Protective efficacy at low antibody doses was observed in a murine model of
      bacteremia. The mode of action in vivo was investigated by using aglycosylated
      derivatives of the protective MAbs. The significant binding to live E. coli cells
      and the in vitro and in vivo efficacy were corroborated in assays using bacteria
      grown in human serum to mimic relevant clinical conditions. Given the dry
      pipeline of novel antibiotics against multidrug-resistant Gram-negative
      pathogens, passive immunization with bactericidal antibodies offers a therapeutic
      alternative to control infections caused by E. coli ST131-O25b:H4.

PMID- 25779572
TI  - In vitro drug combination studies of Letermovir (AIC246, MK-8228) with approved
      anti-human cytomegalovirus (HCMV) and anti-HIV compounds in inhibition of HCMV
      and HIV replication.
AB  - Despite modern prevention and treatment strategies, human cytomegalovirus (HCMV)
      remains a common opportunistic pathogen associated with serious morbidity and
      mortality in immunocompromised individuals, such as transplant recipients and
      AIDS patients. All drugs currently licensed for the treatment of HCMV infection
      target the viral DNA polymerase and are associated with severe toxicity issues
      and the emergence of drug resistance. Letermovir (AIC246, MK-8228) is a new anti
      HCMV agent in clinical development that acts via a novel mode of action and has
      demonstrated anti-HCMV activity in vitro and in vivo. For the future, drug
      combination therapies, including letermovir, might be indicated under special
      medical conditions, such as the emergence of multidrug-resistant virus strains in
      transplant recipients or in HCMV-HIV-coinfected patients. Accordingly, knowledge
      of the compatibility of letermovir with other HCMV or HIV antivirals is of
      medical importance. Here, we evaluated the inhibition of HCMV replication by
      letermovir in combination with all currently approved HCMV antivirals using cell
      culture checkerboard assays. In addition, the effects of letermovir on the
      antiviral activities of selected HIV drugs, and vice versa, were analyzed. Using
      two different mathematical techniques to analyze the experimental data, (i)
      additive effects were observed for the combination of letermovir with anti-HCMV
      drugs and (ii) no interaction was found between letermovir and anti-HIV drugs.
      Since none of the tested drug combinations significantly antagonized letermovir
      efficacy (or vice versa), our findings suggest that letermovir may offer the
      potential for combination therapy with the tested HCMV and HIV drugs.

PMID- 25779573
TI  - Limited transmission of bla(CTX-M-9)-type-positive Escherichia coli between
      humans and poultry in Vietnam.
AB  - We examined whether Escherichia coli isolates that produce CTX-M-9-type extended
      spectrum beta-lactamases (ESBL) are transferred between humans and chickens in a
      Vietnamese community. The phylogenetic group compositions, sequence types,
      antimicrobial resistance profiles, the prevalence of plasmid antibiotic
      resistance genes, and the plasmid replicon types generally differed between the
      human and chicken E. coli isolates. Our results suggest that transmission of the
      bla(CTX-M-9)-positive E. coli between humans and poultry was limited.

PMID- 25779574
TI  - agr dysfunction affects staphylococcal cassette chromosome mec type-dependent
      clinical outcomes in methicillin-resistant Staphylococcus aureus bacteremia.
AB  - Staphylococcal cassette chromosome mec element (SCCmec) type-dependent clinical
      outcomes may vary due to geographical variation in the presence of virulence
      determinants. We compared the microbiological factors and mortality attributed to
      methicillin-resistant Staphylococcus aureus (MRSA) bacteremia between SCCmec
      types II/III and type IV. All episodes of MRSA bacteremia in a tertiary-care
      hospital (South Korea) over a 4.5-year period were reviewed. We studied the
      microbiological factors associated with all blood MRSA isolates, including spa
      type, agr type, agr dysfunction, and the genes for Panton-Valentine leukocidin
      (PVL) and phenol-soluble modulin (PSM)-mec, in addition to SCCmec type. Of 195
      cases, 137 involved SCCmec types II/III, and 58 involved type IV. The mortality
      attributed to MRSA bacteremia was less frequent among the SCCmec type IV (5/58)
      than that among types II/III (39/137, P = 0.002). This difference remained
      significant when adjusted for clinical factors (adjusted odds ratio [aOR], 0.14;
      95% confidence interval [CI], 0.04 to 0.49; P = 0.002). Of the microbiological
      factors tested, agr dysfunction was the only significant factor that showed
      different positivity between the SCCmec types, and it was independently
      associated with MRSA bacteremia-attributed mortality (aOR, 4.71; 95% CI, 1.72 to
      12.92; P = 0.003). SCCmec type IV is associated with lower MRSA bacteremia
      attributed mortality than are types II/III, which might be explained by the high
      rate of agr dysfunction in SCCmec types II/III in South Korea.

PMID- 25779575
TI  - Squalestatin is an inhibitor of carotenoid biosynthesis in Plasmodium falciparum.
AB  - The increasing resistance of malaria parasites to almost all available drugs
      calls for the characterization of novel targets and the identification of new
      compounds. Carotenoids are polyisoprenoids from plants, algae, and some bacteria,
      and they are biosynthesized by Plasmodium falciparum but not by mammalian cells.
      Biochemical and reverse genetics approaches were applied to demonstrate that
      phytoene synthase (PSY) is a key enzyme for carotenoid biosynthesis in P.
      falciparum and is essential for intraerythrocytic growth. The known PSY inhibitor
      squalestatin reduces biosynthesis of phytoene and kills parasites during the
      intraerythrocytic cycle. PSY-overexpressing parasites showed increased
      biosynthesis of phytoene and its derived product phytofluene and presented a
      squalestatin-resistant phenotype, suggesting that this enzyme is the primary
      target of action of this drug in the parasite.

PMID- 25779576
TI  - In vitro antimalarial activity of novel semisynthetic nocathiacin I antibiotics.
AB  - Presently, the arsenal of antimalarial drugs is limited and needs to be
      replenished. We evaluated the potential antimalarial activity of two water
      soluble derivatives of nocathiacin (BMS461996 and BMS411886) against the asexual
      blood stages of Plasmodium falciparum. Nocathiacins are a thiazolyl peptide group
      of antibiotics, are structurally related to thiostrepton, have potent activity
      against a wide spectrum of multidrug-resistant Gram-positive bacteria, and
      inhibit protein synthesis. The in vitro growth inhibition assay was done using
      three laboratory strains of P. falciparum displaying various levels of
      chloroquine (CQ) susceptibility. Our results indicate that BMS461996 has potent
      antimalarial activity and inhibits parasite growth with mean 50% inhibitory
      concentrations (IC50s) of 51.55 nM for P. falciparum 3D7 (CQ susceptible), 85.67
      nM for P. falciparum Dd2 (accelerated resistance to multiple drugs [ARMD]), and
      99.44 nM for P. falciparum K1 (resistant to CQ, pyrimethamine, and sulfadoxine).
      Similar results at approximately 7-fold higher IC50s were obtained with BMS411886
      than with BMS461996. We also tested the effect of BMS491996 on gametocytes; our
      results show that at a 20-fold excess of the mean IC50, gametocytes were deformed
      with a pyknotic nucleus and growth of stage I to IV gametocytes was arrested.
      This preliminary study shows a significant potential for nocathiacin analogues to
      be developed as antimalarial drug candidates and to warrant further
      investigation.

PMID- 25779577
TI  - Implication of Candida parapsilosis FKS1 and FKS2 mutations in reduced
      echinocandin susceptibility.
AB  - We evaluated FKS1 and FKS2 mutations in Candida parapsilosis bloodstream isolates
      and correlated them with the echinocandin MIC values determined by guidelines in
      CLSI document M27-A3 and the YeastOne panel. All mutations detected were outside
      hot spot (HS) regions. The F1386S mutation detected in an isolate that was
      resistant by the YeastOne panel but not by the M27-A3 guidelines might be
      implicated in echinocandin resistance. Further studies are needed to confirm the
      implication of the F1386S mutation and to elucidate the capability of the M27-A3
      guidelines to detect echinocandin resistance.

PMID- 25779578
TI  - A novel gene amplification causes upregulation of the PatAB ABC transporter and
      fluoroquinolone resistance in Streptococcus pneumoniae.
AB  - Overexpression of the ABC transporter genes patA and patB confers efflux-mediated
      fluoroquinolone resistance in Streptococcus pneumoniae and is also linked to
      pneumococcal stress responses. Although upregulation of patAB has been observed
      in many laboratory mutants and clinical isolates, the regulatory mechanisms
      controlling expression of these genes are unknown. In this study, we aimed to
      identify the cause of high-level constitutive overexpression of patAB in M184, a
      multidrug-resistant mutant of S. pneumoniae R6. Using a whole-genome
      transformation and sequencing approach, we identified a novel duplication of a
      9.2-kb region of the M184 genome which included the patAB genes. This duplication
      did not affect growth and was semistable with a low segregation rate. The
      expression levels of patAB in M184 were much higher than those that could be
      fully explained by doubling of the gene dosage alone, and inactivation of the
      first copy of patA had no effect on multidrug resistance. Using a green
      fluorescent protein reporter system, increased patAB expression was ascribed to
      transcriptional read-through from a tRNA gene upstream of the second copy of
      patAB. This is the first report of a large genomic duplication causing antibiotic
      resistance in S. pneumoniae and also of a genomic duplication causing antibiotic
      resistance by a promoter switching mechanism.

PMID- 25779581
TI  - Complete nucleotide sequence of a conjugative plasmid carrying bla(PER-1).
AB  - The nucleotide sequence of a self-transmissible plasmid pVPH1 harboring bla(PER
      1) from Vibrio parahaemolyticus was determined. pVPH1 was 183,730 bp in size and
      shared a backbone similar to pAQU1 and pAQU2, differing mainly in an ~40-kb
      multidrug resistance (MDR) region. A complex class 1 integron was identified
      together with ISCR1 and bla(PER-1) (ISCR1-bla(PER-1)-gst-abct-qacEDelta1-sul1),
      which was shown to form a circular intermediate playing an important role in the
      dissemination of bla(PER-1).

PMID- 25779580
TI  - Achieving target voriconazole concentrations more accurately in children and
      adolescents.
AB  - Despite the documented benefit of voriconazole therapeutic drug monitoring,
      nonlinear pharmacokinetics make the timing of steady-state trough sampling and
      appropriate dose adjustments unpredictable by conventional methods. We developed
      a nonparametric population model with data from 141 previously richly sampled
      children and adults. We then used it in our multiple-model Bayesian adaptive
      control algorithm to predict measured concentrations and doses in a separate
      cohort of 33 pediatric patients aged 8 months to 17 years who were receiving
      voriconazole and enrolled in a pharmacokinetic study. Using all available samples
      to estimate the individual Bayesian posterior parameter values, the median
      percent prediction bias relative to a measured target trough concentration in the
      patients was 1.1% (interquartile range, -17.1 to 10%). Compared to the actual
      dose that resulted in the target concentration, the percent bias of the predicted
      dose was -0.7% (interquartile range, -7 to 20%). Using only trough concentrations
      to generate the Bayesian posterior parameter values, the target bias was 6.4%
      (interquartile range, -1.4 to 14.7%; P = 0.16 versus the full posterior parameter
      value) and the dose bias was -6.7% (interquartile range, -18.7 to 2.4%; P =
      0.15). Use of a sample collected at an optimal time of 4 h after a dose, in
      addition to the trough concentration, resulted in a nonsignificantly improved
      target bias of 3.8% (interquartile range, -13.1 to 18%; P = 0.32) and a dose bias
      of -3.5% (interquartile range, -18 to 14%; P = 0.33). With the nonparametric
      population model and trough concentrations, our control algorithm can accurately
      manage voriconazole therapy in children independently of steady-state conditions,
      and it is generalizable to any drug with a nonparametric pharmacokinetic model.
      (This study has been registered at ClinicalTrials.gov under registration no.
      NCT01976078.).

PMID- 25779579
TI  - Results of a multinational study suggest the need for rapid diagnosis and early
      antiviral treatment at the onset of herpetic meningoencephalitis.
AB  - Data in the literature regarding the factors that predict unfavorable outcomes in
      adult herpetic meningoencephalitis (HME) cases are scarce. We conducted a
      multicenter study in order to provide insights into the predictors of HME
      outcomes, with special emphasis on the use and timing of antiviral treatment.
      Samples from 501 patients with molecular confirmation from cerebrospinal fluid
      were included from 35 referral centers in 10 countries. Four hundred thirty-eight
      patients were found to be eligible for the analysis. Overall, 232 (52.9%)
      patients experienced unfavorable outcomes, 44 died, and 188 survived, with
      sequelae. Age (odds ratio [OR], 1.04; 95% confidence interval [CI], 1.02 to
      1.05), Glasgow Coma Scale score (OR, 0.84; 95% CI, 0.77 to 0.93), and symptomatic
      periods of 2 to 7 days (OR, 1.80; 95% CI, 1.16 to 2.79) and >7 days (OR, 3.75;
      95% CI, 1.72 to 8.15) until the commencement of treatment predicted unfavorable
      outcomes. The outcome in HME patients is related to a combination of therapeutic
      and host factors. This study suggests that rapid diagnosis and early
      administration of antiviral treatment in HME patients are keys to a favorable
      outcome.

PMID- 25779582
TI  - Artemisinin-resistant Plasmodium falciparum parasites exhibit altered patterns of
      development in infected erythrocytes.
AB  - Artemisinin derivatives are used in combination with other antimalarial drugs for
      treatment of multidrug-resistant malaria worldwide. Clinical resistance to
      artemisinin recently emerged in southeast Asia, yet in vitro phenotypes for
      discerning mechanism(s) of resistance remain elusive. Here, we describe novel
      phenotypic resistance traits expressed by artemisinin-resistant Plasmodium
      falciparum. The resistant parasites exhibit altered patterns of development that
      result in reduced exposure to drug at the most susceptible stage of development
      in erythrocytes (trophozoites) and increased exposure in the most resistant stage
      (rings). In addition, a novel in vitro delayed clearance assay (DCA) that
      assesses drug effects on asexual stages was found to correlate with parasite
      clearance half-life in vivo as well as with mutations in the Kelch domain gene
      associated with resistance (Pf3D7_1343700). Importantly, all of the resistance
      phenotypes were stable in cloned parasites for more than 2 years without drug
      pressure. The results demonstrate artemisinin-resistant P. falciparum has evolved
      a novel mechanism of phenotypic resistance to artemisinin drugs linked to
      abnormal cell cycle regulation. These results offer insights into a novel
      mechanism of drug resistance in P. falciparum and new tools for monitoring the
      spread of artemisinin resistance.

PMID- 25779584
TI  - Evolution and single-nucleotide polymorphisms in methicillin-resistant
      Staphylococcus aureus strains with reduced susceptibility to vancomycin and
      daptomycin, based on determination of the complete genome.
AB  - We obtained a series of methicillin-resistant Staphylococcus aureus isolates,
      including both daptomycin-susceptible strain TD1 and daptomycin-resistant strain
      TD4, from a patient. We determined the complete genome sequences of TD1 and TD4
      using next-generation sequencing, and only four single-nucleotide polymorphisms
      (SNPs) were identified, one each in capB (E58K), rpoB (H481Y), lytN (I16V), and
      mprF (V351E). We determined that these four SNPs were sufficient to cause the
      strains to develop daptomycin, vancomycin, and rifampin resistance.

PMID- 25779583
TI  - Cavitary penetration of levofloxacin among patients with multidrug-resistant
      tuberculosis.
AB  - A better understanding of second-line drug (SLD) pharmacokinetics, including
      cavitary penetration, may help optimize SLD dosing. Patients with pulmonary
      multidrug-resistant tuberculosis (MDR-TB) undergoing adjunctive surgery were
      enrolled in Tbilisi, Georgia. Serum was obtained at 0, 1, 4, and 8 h and at the
      time of cavitary removal to measure levofloxacin concentrations. After surgery,
      microdialysis was performed using the ex vivo cavity, and levofloxacin
      concentrations in the collected dialysate fluid were measured. Noncompartmental
      analysis was performed, and a cavitary-to-serum levofloxacin concentration ratio
      was calculated. Twelve patients received levofloxacin for a median of 373 days
      before surgery (median dose, 11.8 mg/kg). The median levofloxacin concentration
      in serum (Cmax) was 6.5 MUg/ml, and it was <2 MUg/ml in 3 (25%) patients. Among
      11 patients with complete data, the median cavitary concentration of levofloxacin
      was 4.36 MUg/ml (range, 0.46 to 8.82). The median cavitary/serum levofloxacin
      ratio was 1.33 (range, 0.63 to 2.36), and 7 patients (64%) had a ratio of >1.
      There was a significant correlation between serum and cavitary concentrations (r
      = 0.71; P = 0.01). Levofloxacin had excellent penetration into chronic cavitary
      TB lesions, and there was a good correlation between serum and cavitary
      concentrations. Optimizing serum concentrations will help ensure optimal cavitary
      concentrations of levofloxacin, which may enhance treatment outcomes. 

PMID- 25779585
TI  - Subtype-specific analysis of the K65R substitution in HIV-1 that confers
      hypersusceptibility to a novel nucleotide-competing reverse transcriptase
      inhibitor.
AB  - Compound A is a novel nucleotide-competing HIV-1 reverse transcriptase (RT)
      inhibitor (NcRTI) that selects for a unique W153L substitution that confers
      hypersusceptibility to tenofovir, while the K65R substitution in RT confers
      resistance against tenofovir and enhances susceptibility to NcRTIs. Although the
      K65R substitution is more common in subtype C viruses, the impact of subtype
      variability on NcRTI susceptibility has not been studied. In the present study,
      we performed experiments with compound A by using purified recombinant RT enzymes
      and viruses of subtypes B and C and circulating recombinant form CRF_A/G. We
      confirmed the hypersusceptibility of K65R substitution-containing RTs to compound
      A for subtype C, CRF_A/G, and subtype B. Steady-state kinetic analysis showed
      that K65R RTs enhanced the susceptibility to compound A by increasing binding of
      the inhibitor to the nucleotide binding site of RT in a subtype-independent
      manner, without significantly discriminating against the natural nucleotide
      substrate. These data highlight the potential utility of NcRTIs, such as compound
      A, for treatment of infections with K65R substitution-containing viruses,
      regardless of HIV-1 subtype.

PMID- 25779586
TI  - The new macrolide-lincosamide-streptogramin B resistance gene erm(45) is located
      within a genomic island in Staphylococcus fleurettii.
AB  - Genome alignment of a macrolide, lincosamide, and streptogramin B (MLSB)
      resistant Staphylococcus fleurettii strain with an MLSB-susceptible S. fleurettii
      strain revealed a novel 11,513-bp genomic island carrying the new erythromycin
      resistance methylase gene erm(45). This gene was shown to confer inducible MLSB
      resistance when cloned into Staphylococcus aureus. The erm(45)-containing island
      was integrated into the housekeeping gene guaA in S. fleurettii and was able to
      form a circular intermediate but was not transmissible to S. aureus. 

PMID- 25779588
TI  - Update on the UK law on consent.

PMID- 25779587
TI  - Predominance of KPC-3 in a survey for carbapenemase-producing Enterobacteriaceae
      in Portugal.
AB  - Among the 2,105 Enterobacteriaceae tested in a survey done in Portugal, 165 were
      nonsusceptible to carbapenems, from which 35 (26 Klebsiella pneumoniae, 3
      Escherichia coli, 2 Enterobacter aerogenes, and 3 Enterobacter cloacae isolates
      and 1 Klebsiella oxytoca isolate) were confirmed to be carbapenemase producers by
      the presence of 30 Tn4401d-blaKPC-3, 4 intI3-blaGES-5, and one intI1-blaVIM-2
      gene, alone or in combination with other bla genes. The dissemination of blaKPC-3
      gene carried by an IncF plasmid suggests lateral gene transfer as a major
      mechanism of dissemination.

PMID- 25779589
TI  - HIV-1 splicing is controlled by local RNA structure and binding of splicing
      regulatory proteins at the major 5' splice site.
AB  - The 5' leader region of the human immunodeficiency virus 1 (HIV-1) RNA genome
      contains the major 5' splice site (ss) that is used in the production of the many
      spliced viral RNAs. This splice-donor (SD) region can fold into a stable stem
      loop structure and the thermodynamic stability of this RNA hairpin influences
      splicing efficiency. In addition, splicing may be modulated by binding of
      splicing regulatory (SR) proteins, in particular SF2/ASF (SRSF1), SC35 (SRSF2),
      SRp40 (SRSF5) and SRp55 (SRSF6), to sequence elements in the SD region. The role
      of RNA structure and SR protein binding in splicing control was previously
      studied by functional analysis of mutant SD sequences. The interpretation of
      these studies was complicated by the fact that most mutations simultaneously
      affect both structure and sequence elements. We therefore tried to disentangle
      the contribution of these two variables by designing more precise SD region
      mutants with a single effect on either the sequence or the structure. The current
      analysis indicates that HIV-1 splicing at the major 5'ss is modulated by both the
      stability of the local RNA structure and the binding of splicing regulatory
      proteins. 

PMID- 25779590
TI  - First rotavirus vaccine made in India is launched.

PMID- 25779591
TI  - The ESR Patient Advisory Group (ESR-PAG).
AB  - The European Society of Radiology (ESR) Patient Advisory Group addresses the
      issue of communication among radiologists, radiographers and their patients.
      Initiated in 2013, the group represents many patient groups, working together
      with the ESR to raise awareness of medical imaging amongst patients, improve
      patient knowledge about imaging procedures, liaise on policy issues of common
      interest, involve patient representatives in strategic decisions regarding
      medical imaging and ensure that a patient-centred, "human" approach is embedded
      in the structure of the ESR. The ESR strongly believes that close collaboration
      with patient organisations is beneficial for both stakeholders, helping
      radiologists to understand patients' needs, to adapt their practice accordingly
      and to improve their communication skills. These factors are important to help
      radiologists find acknowledgement as clinicians and overcome the specialty's poor
      visibility. Close collaboration with professionals will allow patients to obtain
      a better understanding of the work of everyone involved in a radiological
      department, of the advantages and limitations of imaging, and what to expect from
      a radiological examination or an imaging-guided interventional procedure. Thus,
      this collaborative effort is not simply limited to improving patient
      satisfaction; the ultimate goal is to enhance the faith and trust that patients
      place in the medical imaging profession and all the radiology professionals
      involved. MAIN MESSAGES: * Good communication between patient and doctor is
      important for proper patient care. * The ESR Patient Advisory Group specifically
      addresses this communication issue. * The activities aim at developing a
      reciprocal relationship between radiologists/radiographers and patients. * Both
      radiologists/radiographers and patients need to be "educated" to improve
      communication.

PMID- 25779596
TI  - How Pakistan's media spreads the message about reproductive and sexual health.

PMID- 25779597
TI  - Gastric adenocarcinoma screening and prevention in the era of new biomarker and
      endoscopic technologies: a cost-effectiveness analysis.
AB  - OBJECTIVE: To estimate the cost-effectiveness of noncardia gastric adenocarcinoma
      (NCGA) screening strategies based on new biomarker and endoscopic technologies.
      DESIGN: Using an intestinal-type NCGA microsimulation model, we evaluated the
      following one-time screening strategies for US men: (1) serum pepsinogen to
      detect gastric atrophy (with endoscopic follow-up of positive screen results),
      (2) endoscopic screening to detect dysplasia and asymptomatic cancer (with
      endoscopic mucosal resection (EMR) treatment for detected lesions) and (3)
      Helicobacter pylori screening and treatment. Screening performance, treatment
      effectiveness, cancer and cost data were based on published literature and
      databases. Subgroups included current, former and never smokers. Outcomes
      included lifetime cancer risk and incremental cost-effectiveness ratios (ICERs),
      expressed as cost per quality-adjusted-life-year (QALY) gained. RESULTS:
      Screening the general population at age 50 years reduced the lifetime intestinal
      type NCGA risk (0.24%) by 26.4% with serum pepsinogen screening, 21.2% with
      endoscopy and EMR and 0.2% with H. pylori screening/treatment. Targeting current
      smokers reduced the lifetime risk (0.35%) by 30.8%, 25.5%, and 0.1%,
      respectively. For all subgroups, serum pepsinogen screening was more effective
      and more cost-effective than all other strategies, although its ICER varied from
      $76,000/QALY (current smokers) to $105,400/QALY (general population). Results
      were sensitive to H. pylori prevalence, screen age and serum pepsinogen test
      sensitivity. Probabilistic sensitivity analysis found that at a $100,000/QALY
      willingness-to-pay threshold, the probability that serum pepsinogen screening was
      preferred was 0.97 for current smokers. CONCLUSIONS: Although not warranted for
      the general population, targeting high-risk smokers for serum pepsinogen
      screening may be a cost-effective strategy to reduce intestinal-type NCGA
      mortality.

PMID- 25779598
TI  - Gastric tumour-derived ANGPT2 regulation by DARPP-32 promotes angiogenesis.
AB  - OBJECTIVE: Overexpression of dopamine and cAMP-regulated phosphoprotein, Mr 32000
      (DARPP-32), and its truncated isoform (t-DARPP) are associated with gastric
      tumorigenesis. Herein, we investigated the role of DARPP-32 proteins in
      regulating angiopoietin 2 (ANGPT2) and promoting tumour angiogenesis. DESIGN:
      Quantitative real-time RT-PCR, immunoblotting, luciferase reporter,
      immunofluorescence, immunohistochemistry and angiogenesis assays were applied to
      investigate the regulation of angiogenesis by DARPP-32 proteins. RESULTS:
      Overexpression of DARPP-32 significantly increased the mRNA and protein levels of
      ANGPT2 in gastric cancer cells. The overexpression of DARPP-32 T34A mutant or the
      N-terminal truncated isoform, t-DARPP, led to similar effects ruling out the T34
      dependent regulation of protein phosphatase 1 activity in regulating ANGPT2.
      DARPP-32 proteins induced a secreted form of ANGPT2, which was detectable in the
      media, functionally active, and able to induce angiogenesis, measured by the
      human umbilical vein endothelial cells tube formation assay. Antibody blocking of
      the secreted ANGPT2 abrogated its function. To identify the mechanism by which
      DARPP-32 regulates ANGPT2, we examined the activities of NF-kappaB and signal
      transducer and activator of transcription 3 (STAT3), known regulators of
      angiogenesis. The results ruled out NF-kappaB and showed induction of STAT3
      phosphorylation, activation and nuclear localisation. Inhibition or knockdown of
      STAT3 significantly attenuated the induction of ANGPT2 by DARPP-32 proteins. In
      vivo xenograft models demonstrated that overexpression of DARPP-32 promotes
      angiogenesis and tumour growth. Analyses of human gastric cancer tissues showed a
      strong correlation between DARPP-32 and ANGPT2. CONCLUSIONS: Our novel findings
      establish the role of DARPP-32-STAT3 axis in regulating ANGPT2 in cancer cells to
      promote angiogenesis and tumorigenesis.

PMID- 25779599
TI  - The neuropsychological assessment of cognitive deficits considering measures of
      performance variability.
AB  - Neuropsychologists often face interpretational difficulties when assessing
      cognitive deficits, particularly in cases of unclear cerebral etiology. How can
      we be sure whether a single test score below the population average is indicative
      of a pathological brain condition or normal? In the past few years, the topic of
      intra-individual performance variability has gained great interest. On the basis
      of a large normative sample, two measures of performance variability and their
      importance for neuropsychological interpretation will be presented in this paper:
      the number of low scores and the level of dispersion. We conclude that low scores
      are common in healthy individuals. On the other hand, the level of dispersion is
      relatively small. Here, base rate information about abnormally low scores and
      abnormally high dispersion across cognitive abilities are provided to improve the
      awareness of normal variability and to serve clinicians as additional
      interpretive measures in the diagnostic process. 

PMID- 25779600
TI  - The Interchangeability of CVLT-II and WMS-IV Verbal Paired Associates Scores: A
      Slightly Different Story.
AB  - We investigated the similarity of the Wechsler Memory Scale-Fourth Edition (WMS
      IV) Auditory Memory Index (AMI) scores when California Verbal Learning Test
      Second Edition (CVLT-II) scores are substituted for WMS-IV Verbal Paired
      Associates (VPA) subtest scores. College students (n = 103) were administered
      select WMS-IV subtests and the CVLT-II in a randomized order. Immediate and
      delayed VPA scaled scores were significantly greater than VPA substitute scaled
      scores derived from CVLT-II performance. At the Index level, AMI scores were
      significantly lower when CVLT-II scores were used in place of VPA scores. It is
      important that clinicians recognize the accepted substitution of CVLT-II scores
      can result in WMS-IV scores that are inconsistent with those derived from
      standard administration. Psychometric issues that plausibly contribute to these
      differences and clinical implications are discussed.

PMID- 25779601
TI  - Paediatric use of melatonin.

PMID- 25779602
TI  - More data are needed for Essure hysteroscopic sterilization device.

PMID- 25779603
TI  - Radiographic Progression of Patients With Psoriatic Arthritis Who Achieve Minimal
      Disease Activity in Response to Golimumab Therapy: Results Through 5 Years of a
      Randomized, Placebo-Controlled Study.
AB  - OBJECTIVE: To evaluate long-term outcomes in psoriatic arthritis (PsA) patients
      who achieved or did not achieve minimal disease activity (MDA) through 5 years of
      golimumab treatment in the GO-REVEAL trial. METHODS: The GO-REVEAL trial was a
      phase III, randomized, double-blind trial with placebo-control through week 24
      followed by an open-label extension of golimumab 50/100 mg treatment up to 5
      years. In these post-hoc analyses, MDA was defined by the presence of >=5 of 7
      PsA outcome measures (<=1 swollen joint, <=1 tender joint, Psoriasis Area and
      Severity Index [PASI] <=1, patient pain score <=15, patient global disease
      activity score <=20 [range 0-100], Health Assessment Questionnaire disability
      index [HAQ DI] <=0.5, and <=1 tender enthesis point). RESULTS: Treatment with
      golimumab yielded significantly higher MDA response rates versus patients
      randomized to placebo at week 14 (23.5% versus 1.0%; P < 0.0001), week 24 (28.1%
      versus 7.7%; P < 0.0001), and week 52 (42.4% versus 30.2%; P = 0.037). MDA was
      achieved at least once by ~50% of golimumab-treated patients overall.
      Irrespective of treatment randomization, achievement of MDA at >=3 and >=4
      consecutive visits was associated with significantly less radiographic
      progression and more improvement in MDA components allowing specific assessment
      of physical function (HAQ DI) and overall disease activity (patient global
      assessment of disease activity) at week 256 versus patients not achieving MDA.
      Logistic regression analyses indicated that a 1-unit higher baseline HAQ DI score
      yielded a significantly lower likelihood of achieving MDA at >=3 (odds ratio
      0.514 [95% confidence interval 0.321-0.824]; P = 0.006) and >=4 (odds ratio 0.480
      [95% confidence interval 0.290-0.795]; P = 0.004) consecutive visits. CONCLUSION:
      Among golimumab-treated PsA patients, better long-term functional improvement,
      patient global assessment, and radiographic outcomes were observed when patients
      achieved persistent MDA.

PMID- 25779604
TI  - Comprehensive characterization of temperature- and pressure-induced bilayer phase
      transitions for saturated phosphatidylcholines containing longer chain homologs.
AB  - Complete elucidation of the phase behavior of phospholipid bilayers requires
      information on the subtransition from the lamellar crystal (Lc) phase to the gel
      phase. However, for bilayers of saturated diacylphosphatidylcholines (CnPCs),
      especially longer chain homologs, equilibration in the Lc phase is known to be
      very slow. In this study, bilayer phase transitions of three CnPCs with longer
      acyl chains, C19PC, C20PC and C21PC, were observed by differential scanning
      calorimetry under atmospheric pressure and by light-transmittance measurements
      under high pressure. Using lipid samples treated by thermal annealing enabled the
      observation of the sub-, pre- and main transitions of the C19PC and C20PC
      bilayers under atmospheric pressure. Only the pre- and main transitions could be
      observed for the C21PC bilayer due to very slow kinetics of the Lc phase
      formation for lipids with long acyl chains. The temperature and pressure phase
      diagrams constructed and phase-transitions quantities (enthalpy, entropy and
      volume changes) evaluated for these bilayers were compared with one another and
      with those of bilayers of the CnPC homologs examined in previous studies. These
      results allowed us (1) to clarify the temperature- and pressure-dependent phase
      sequence and phase stability of the CnPC (n=12-22) bilayers as a function of the
      hydrophobicity of the molecules, (2) to prove the presence of a shorter and a
      longer limit (n=13 and 21) in the acyl chain length for the pressure-induced
      bilayer interdigitation and (3) to reveal the chain-length dependence of the
      thermodynamic quantities of the subtransitions including the volume change. 

PMID- 25779605
TI  - Rapamycin loaded magnetic Fe3O4/carboxymethylchitosan nanoparticles as tumor
      targeted drug delivery system: Synthesis and in vitro characterization.
AB  - A novel tumor-targeted drug delivery system (Fe3O4/CMCS-Rapa NPs) was prepared
      using magnetic Fe3O4/carboxymethylchitosan nanoparticles (Fe3O4/CMCS NPs) as
      carrier and rapamycin (Rapa) as the model anti-tumor drug. The morphology,
      composition, and properties of the Fe3O4/CMCS-Rapa NPs were characterized by
      Fourier transform infrared spectroscopy (FT-IR), transmission electron microscope
      (TEM), X-ray diffraction (XRD), thermal analysis (TG/DSC), vibration sample
      magnetometer (VSM), and drug release kinetics, cytotoxicity, cellular uptake,
      apoptosis studies in vitro. The results showed that the synthesized Fe3O4/CMCS
      Rapa NPs were spherical in shape with an average size of 30+/-2 nm, the saturated
      magnetization reached 67.1 emu/g, and the loading efficiency of Rapa was
      approximately 6.32+/-0.34%. In addition, the in vitro drug release behavior
      displayed that the Fe3O4/CMCS NPs exhibited a biphasic drug release pattern with
      initial burst release and consequently sustained release. Furthermore, the
      Fe3O4/CMCS-Rapa NPs showed lower cytotoxicity to liver cell line (LO2) and
      comparatively higher cytotoxicity to human hepatocarcinoma cell line (HepG2) than
      native Rapa. Fe3O4/CMCS-Rapa NPs could enhance cellular uptake and reduce Rapa
      drug damage to the normal cells so as to improve the curative effect of drug to
      tumor cells. All these results demonstrated that the Fe3O4/CMCS-Rapa NPs may be
      useful as a promising candidate for targeted cancer diagnostic and therapy.

PMID- 25779606
TI  - RETRACTED: Enhanced antitumor efficacy of 5-fluorouracil loaded methoxy
      poly(ethylene glycol)-poly(lactide) nanoparticles for efficient therapy against
      breast cancer.
AB  - In the present study, a novel nanocarrier was developed for the delivery of
      anticancer drug to the cancer tissues. For this purpose, 5-FU loaded methoxy
      poly(ethylene glycol)-poly(lactide) (mPEG-PLA) (5-FU NP) based polymeric
      nanoparticles was designed to increase the chemotherapeutic efficacy against
      breast cancers. Nanoprecipitation method was used to prepare the drug-loaded
      nanoparticles. The nanoparticle was evaluated in terms of DLS, TEM, in vitro
      release kinetics, and in vivo parameters. The average particle diameter of drug
      loaded NP was ~110 nm and exhibited a sustained drug release pattern for up to
      120 h. The NP exhibited a pH-response drug release pattern with accelerated
      release at acidic media. The in vitro cytotoxicity assay showed the enhanced
      cytotoxicity effect of NP formulations in comparison to free drug. The NP system
      showed remarkable G2/M phase cell cycle arrest with significant amount of
      apoptosis cells in late and early phase of flow cytometer analysis. Consistently,
      NP formulation greatly decreased the tumor burden of mice with no sign of adverse
      effect. TUNEL assay further confirmed the superior anticancer effect of NP
      formulations which showed a high number of apoptotic cells. The favorable results
      obtained from this study highlights the potential application of encapsulated 5
      FU NP in the treatment of breast cancers. The remarkable anticancer therapeutic
      efficacy with negligible toxicity profile of 5-FU NP makes it one of the possible
      alternative for the successful breast cancer therapy.

PMID- 25779607
TI  - 3D analysis of condylar remodelling and skeletal relapse following bilateral
      sagittal split advancement osteotomies.
AB  - A major concern in mandibular advancement surgery using bilateral sagittal split
      osteotomies (BSSO) is potential postoperative relapse. Although the role of
      postoperative changes in condylar morphology on skeletal relapse was reported in
      previous studies, no study so far has objectified the precise changes of the
      condylar volume. The aim of the present study was to quantify the postoperative
      volume changes of condyles and its role on skeletal stability following BSSO
      mandibular advancement surgery. A total of 56 patients with mandibular hypoplasia
      who underwent BSSO advancement surgery were prospectively enrolled into the
      study. A cone beam computed tomography (CBCT) scan was acquired preoperatively,
      at 1 week postoperatively and at 1 year postoperatively. After the segmentation
      of the facial skeleton and condyles, three-dimensional cephalometry and condylar
      volume analysis were performed. The mean mandibular advancement was 4.6 mm, and
      the mean postoperative relapse was 0.71 mm. Of 112 condyles, 55% showed a
      postoperative decrease in condylar volume, with a mean reduction of 105 mm(3)
      (6.1% of the original condylar volume). The magnitude of condylar remodelling
      (CR) was significantly correlated with skeletal relapse (p = 0.003). Patients
      with a CR greater than 17% of the original condylar volume exhibited relapse as
      seen in progressive condylar resorption. Female patients with a high mandibular
      angle who exhibited postoperative CR were particularly at risk for postoperative
      relapse. Gender, preoperative condylar volume, and downward displacement of
      pogonion at surgery were prognostic factors for CR (r(2) = 21%). It could be
      concluded that the condylar volume can be applied as a useful 3D radiographic
      parameter for the diagnosis and follow-up of postoperative skeletal relapse and
      progressive condylar resorption. 

PMID- 25779608
TI  - Aneurysm-like outpouching of ventricular wall through a gap caused by
      constrictive pericarditis with focal sparing.
AB  - Constrictive pericarditis is usually generalized though it can be focal,
      affecting only a patch of pericardium, or very rarely, generalized with focal
      sparing. We describe a case of constrictive pericarditis with focal sparing along
      the right ventricle. This focal sparing behaved like a defect in the otherwise
      thickened pericardium, resulting in protrusion of normal right ventricular
      myocardium between the margins of the thickened pericardium simulating an
      aneurysm. 

PMID- 25779609
TI  - Targeting caveolin-3 for the treatment of diabetic cardiomyopathy.
AB  - Diabetes is a global health problem with more than 550 million people predicted
      to be diabetic by 2030. A major complication of diabetes is cardiovascular
      disease, which accounts for over two-thirds of mortality and morbidity in
      diabetic patients. This increased risk has led to the definition of a diabetic
      cardiomyopathy phenotype characterised by early left ventricular dysfunction with
      normal ejection fraction. Here we review the aetiology of diabetic cardiomyopathy
      and explore the involvement of the protein caveolin-3 (Cav3). Cav3 forms part of
      a complex mechanism regulating insulin signalling and glucose uptake, processes
      that are impaired in diabetes. Further, Cav3 is key for stabilisation and
      trafficking of cardiac ion channels to the plasma membrane and so contributes to
      the cardiac action potential shape and duration. In addition, Cav3 has direct and
      indirect interactions with proteins involved in excitation-contraction coupling
      and so has the potential to influence cardiac contractility. Significantly, both
      impaired contractility and rhythm disturbances are hallmarks of diabetic
      cardiomyopathy. We review here how changes to Cav3 expression levels and altered
      relationships with interacting partners may be contributory factors to several of
      the pathological features identified in diabetic cardiomyopathy. Finally, the
      review concludes by considering ways in which levels of Cav3 may be manipulated
      in order to develop novel therapeutic approaches for treating diabetic
      cardiomyopathy. 

PMID- 25779610
TI  - Allergic contact dermatitis to triethanolamine in a child.
AB  - Triethanolamine is used as an emulsifier in many cosmetics and in topical
      medications, yet the occurrence of contact dermatitis to cosmetics containing
      triethanolamine is rare in childhood. Our case highlights how young age should
      not be a deterrent to investigation and demonstrates the importance of patch
      testing with selected allergens. 

PMID- 25779611
TI  - Another great wannabe..., with fatal outcome.

PMID- 25779612
TI  - Frontier studies on highly selective bio-regulators useful for environmentally
      benign agricultural production.
AB  - Fungal metabolites active for insects were obtained from fermentation products
      using okara media. The mechanisms of action of these compounds against insects
      were clarified using voltage clamp electrophysiology. The branching factor
      inducing hyphal branching in arbuscular mycorrhizal (AM) fungi was isolated from
      the root exudates of Lotus japonicus and identified as 5-deoxystrigol.
      Strigolactones were originally identified as seed germination stimulants of
      parasitic weeds; therefore, synthetic strigolactones were developed to exhibit
      the inducing activity of hyphal branching in AM fungi and diminish the
      stimulating activity of seed germination of parasitic weeds. Signaling molecules,
      acylhomoserine lactones (AHLs), in quorum sensing were identified in the fungal
      strain Mortierella alpina A-178, and the true producer of AHLs was clarified as
      symbiotic bacteria in the fungus. Since acyl-(S)-adenosylmethionine analogs may
      be good candidates for competitive inhibitors of AHL synthases, intermediate
      mimics in the biosynthesis of AHLs have been synthesized. 

PMID- 25779613
TI  - Preparation of AgInS2 quantum dot/In2S3 co-sensitized photoelectrodes by a facile
      aqueous-phase synthesis route and their photovoltaic performance.
AB  - In an aqueous-phase system, AgInS2 quantum dot (QD) sensitized TiO2 photoanodes
      were prepared in situ by the reaction of beta-In2S3 nanocrystals and as-prepared
      TiO2/Ag2S-QD electrodes, followed by a covering process with a ZnS passivation
      layer. A facile successive ionic layer adsorption and reaction (SILAR) method was
      adopted to obtain TiO2/Ag2S-QD electrodes. beta-In2S3 nanocrystals synthesized by
      the chemical bath deposition (CBD) process serve as the reactant of AgInS2 as
      well as a buffer layer between the interfaces of TiO2 and AgInS2-QDs. A
      polysulfide electrolyte and a Pt-coated FTO glass count electrode were used to
      test the photovoltaic performance of the constructed devices. The characteristics
      of the sensitized photoelectrodes were studied in more detail by electron
      microscopy, X-ray techniques, and optical and photoelectric performance
      measurements. AgInS2 is the main photo-sensitizer for TiO2/AgInS2-QD/In2S3
      electrodes and excess In2S3 appears on the surface of the electrodes. Based on
      the optimal Ag2S SILAR cycle, the best photovoltaic performance of the prepared
      TiO2/AgInS2-QD/In2S3 electrode with the short-circuit photocurrent density (Jsc)
      of 7.87 mA cm(-2) and power conversion efficiency (eta) of 0.70% under full one
      sun illumination was achieved. 

PMID- 25779614
TI  - Performance of Liaison XL automated immunoassay platform for blood-borne
      infection screening on hepatitis B, hepatitis C, HIV 1/2, HTLV 1/2 and Treponema
      pallidum serological markers.
AB  - OBJECTIVES: Aim of the study was to evaluate performance of a new fully automated
      platform, DiaSorin-LIAISON(r) XL (DiaSorin S.p.A, Vercelli, Italy), in blood
      donor screening, specifically for hepatitis B surface antigen (HBsAg), hepatitis
      B core antibodies (anti-HBc), hepatitis C antibodies (anti-HCV), HIV p24 antigen,
      HIV antibodies, human T-lymphotropic virus types 1 and 2 (HTLV-1/2) and Treponema
      pallidum antibodies. BACKGROUND: In screening for such viral and bacteriological
      blood-borne infections, sensitivity and specificity are of utmost importance.
      METHODS: Sensitivity was evaluated using selected panels of samples previously
      analysed on the Abbott Architect immunoanalyser (Abbott Laboratories, Abbott
      Park, IL, USA)--the gold standard for this evaluation. These samples were
      confirmed positive for HBsAg, anti-HBc, anti-HCV, HIV Ag/Ab, anti-HTLV-1/2 and
      antibodies to T. pallidum, respectively. Specificity analysis was assessed by
      analysing blood donor samples previously run on the Architect platform and found
      non-reactive for each marker. A total of 1.100 donor samples (both new and
      regular donors) were tested. Previously, non-specific reactive samples were also
      run for every tested marker, as well as samples with autoimmune antibodies and
      antibodies to other infections. RESULTS: Three hundred seventy-eight samples
      positive for the tested markers (HBsAg n = 51, anti-HBc n = 52, anti-HCV n = 75,
      anti-Treponema n = 55, anti-HIV-1 n = 79, anti-HIV-2 n = 25, anti-HIV 1/2 n = 3,
      anti-HTLV-1 n = 28 anti-HTLV-2 n = 10) were tested and found positive, suggesting
      a high sensitivity. A number of 342-1100 negative blood donors (depending on
      marker) have been tested, with very good specificity for the markers tested,
      ranging between 99.5 and 100%, respectively. CONCLUSIONS: The LIAISON(r) XL
      platform demonstrated very high sensitivity for the markers tested and the
      specificity necessary to fulfil the stringent requirements for blood donor
      screening.

PMID- 25779615
TI  - Usefulness of sonication of cardiovascular implantable electronic devices to
      enhance microbial detection.
AB  - The cardiovascular implantable electronic device (CIED) infection rate is rising
      disproportionately to the rate of device implantation. Identification of
      microorganisms that cause CIED infections is not always achieved using present
      laboratory techniques. We conducted a prospective study to determine whether
      device vortexing-sonication followed by culture of the resulting sonicate fluid
      would enhance microbial detection compared with traditional swab or pocket tissue
      cultures. Forty-two subjects with noninfected and 35 with infected CIEDs were
      prospectively enrolled over 12 months. One swab each from the device pocket and
      device surface, pocket tissue, and the CIED were collected from each patient.
      Swabs and tissues were cultured using routine methods. The CIED was processed in
      Ringer's solution using vortexing-sonication and the resultant fluid
      semiquantitatively cultured. Tissue and swab growth was considered significant
      when colonies grew on >=2 quadrants of the culture plate and device was
      considered significant when >=20 colonies were isolated from 10 ml of sonicate
      fluid. In noninfected group, 5% of sonicate fluids yielded significant bacterial
      growth, compared with 5% of tissue cultures (p = 1.00) and 2% of both pocket and
      device swab cultures (p = 0.317 each). In infected group, significant bacterial
      growth was observed in 54% of sonicate fluids, significantly greater than the
      sensitivities of pocket swab (20%, p = 0.001), device swab (9%, p <0.001), or
      tissue (9%, p <0.001) culture. In conclusion, vortexing-sonication of CIEDs with
      semiquantitative culture of the resultant sonicate fluid results in a significant
      increase in the sensitivity of culture results, compared with swab or tissue
      cultures.

PMID- 25779616
TI  - Comparison of left ventricular torsion and strain with biventricular pacing in
      patients with underlying right bundle branch block versus those with left bundle
      branch block.
AB  - The benefits of biventricular pacing in patients with cardiac resynchronization
      therapy (CRT) remain poorly understood in those with right bundle branch block
      (RBBB). The aim of this study was to examine the differences in several speckle
      tracking-derived parameters, including left ventricular torsion and longitudinal
      strain with CRT on and off for patients with underlying left bundle branch block
      (LBBB) and RBBB. Twelve patients with CRT and RBBB were compared with a similar
      group of patients with underlying LBBB who were sent for evaluation and
      atrioventricular optimization. Echocardiographic images were acquired with
      biventricular pacing on and off. The 2 groups had similar baseline
      characteristics, including age, the ejection fraction, and QRS duration. During
      intrinsic conduction (CRT off), patients with LBBB had lower torsion angles than
      those with RBBB (2.3 +/- 1.0 degrees  in those with LBBB vs 6.3 +/- 1.0 degrees 
      in those with RBBB, p = 0.03) but trended toward improvements in torsional
      parameters, including torsional angle and peak untwisting velocity with CRT on,
      whereas these parameters worsened in patients with RBBB. Compared with CRT off,
      analyses of septal and lateral strain curves showed significant improvements in
      septal strain during 100% and 200% of systole with CRT on in patients with LBBB,
      whereas biventricular pacing resulted in a trend toward worsening of septal
      strain in patients with RBBB. Negligible changes were noted in lateral strain
      values. In conclusion, CRT favorably improves regional mechanics in patients with
      LBBB primarily involving the ventricular septum, with a negligible positive
      impact on cardiac function in patients with underlying RBBB.

PMID- 25779617
TI  - Meta-analysis of the impact of mitral regurgitation on outcomes after
      transcatheter aortic valve implantation.
AB  - Significant mitral regurgitation (MR) constitutes an important co-existing
      valvular heart disease burden in the setting of aortic valve stenosis. There are
      conflicting reports on the impact of significant MR on outcomes after
      transcatheter aortic valve implantation (TAVI). We evaluated the impact of MR on
      outcomes after TAVI by performing a meta-analysis of 8 studies involving 8,927
      patients reporting TAVI outcomes based on the presence or absence of moderate
      severe MR. Risk ratios (RRs) were calculated using the inverse variance random
      effects model. None-mild MR was present in 77.8% and moderate-severe MR in 22.2%
      of the patients. The presence of moderate-severe MR at baseline was associated
      with increased mortality at 30 days (RR 1.35, 95% confidence interval [CI] 1.14
      to 1.59, p = 0.003) and 1 year (RR 1.24, 95% CI 1.13 to 1.37, p <0.0001). The
      increased mortality associated with moderate-severe MR was not influenced by the
      cause of MR (functional or degenerative MR; RR 0.90, 95% CI 0.62 to 1.30, p =
      0.56). The severity of MR improved in 61 +/- 6.0% of patients after TAVI.
      Moderate-severe residual MR, compared with none-mild residual MR after TAVI, was
      associated with significantly increased 1-year mortality (RR 1.48, 95% CI 1.31 to
      1.68, p <0.00001). In conclusion, baseline moderate-severe MR and significant
      residual MR after TAVI are associated with an increase in mortality after TAVI
      and represent an important group to target with medical or transcatheter
      therapies in the future.

PMID- 25779618
TI  - Reply: To PMID 25308108.

PMID- 25779619
TI  - Collisions of deformable cells lead to collective migration.
AB  - Collective migration of eukaryotic cells plays a fundamental role in tissue
      growth, wound healing and immune response. The motion, arising spontaneously or
      in response to chemical and mechanical stimuli, is also important for
      understanding life-threatening pathologies, such as cancer and metastasis
      formation. We present a phase-field model to describe the movement of many self
      organized, interacting cells. The model takes into account the main mechanisms of
      cell motility - acto-myosin dynamics, as well as substrate-mediated and cell-cell
      adhesion. It predicts that collective cell migration emerges spontaneously as a
      result of inelastic collisions between neighboring cells: collisions lead to a
      mutual alignment of the cell velocities and to the formation of coherently-moving
      multi-cellular clusters. Small cell-to-cell adhesion, in turn, reduces the
      propensity for large-scale collective migration, while higher adhesion leads to
      the formation of moving bands. Our study provides valuable insight into
      biological processes associated with collective cell motility. 

PMID- 25779620
TI  - A causal loop analysis of the sustainability of integrated community case
      management in Rwanda.
AB  - Expansion of community health services in Rwanda has come with the national scale
      up of integrated Community Case Management (iCCM) of malaria, pneumonia and
      diarrhea. We used a sustainability assessment framework as part of a large-scale
      project evaluation to identify factors affecting iCCM sustainability (2011). We
      then (2012) used causal-loop analysis to identify systems determinants of iCCM
      sustainability from a national systems perspective. This allows us to develop
      three high-probability future scenarios putting the achievements of community
      health at risk, and to recommend mitigating strategies. Our causal loop diagram
      highlights both balancing and reinforcing loops of cause and effect in the
      national iCCM system. Financial, political and technical scenarios carry high
      probability for threatening the sustainability through: (1) reduction in
      performance-based financing resources, (2) political shocks and erosion of
      political commitment for community health, and (3) insufficient progress in
      resolving district health systems--"building blocks"--performance gaps. In a
      complex health system, the consequences of choices may be delayed and hard to
      predict precisely. Causal loop analysis and scenario mapping make explicit
      complex cause-and-effects relationships and high probability risks, which need to
      be anticipated and mitigated. 

PMID- 25779621
TI  - Estimating unbiased economies of scale of HIV prevention projects: a case study
      of Avahan.
AB  - Governments and donors are investing considerable resources on HIV prevention in
      order to scale up these services rapidly. Given the current economic climate,
      providers of HIV prevention services increasingly need to demonstrate that these
      investments offer good 'value for money'. One of the primary routes to achieve
      efficiency is to take advantage of economies of scale (a reduction in the average
      cost of a health service as provision scales-up), yet empirical evidence on
      economies of scale is scarce. Methodologically, the estimation of economies of
      scale is hampered by several statistical issues preventing causal inference and
      thus making the estimation of economies of scale complex. In order to estimate
      unbiased economies of scale when scaling up HIV prevention services, we apply our
      analysis to one of the few HIV prevention programmes globally delivered at a
      large scale: the Indian Avahan initiative. We costed the project by collecting
      data from the 138 Avahan NGOs and the supporting partners in the first four years
      of its scale-up, between 2004 and 2007. We develop a parsimonious empirical model
      and apply a system Generalized Method of Moments (GMM) and fixed-effects
      Instrumental Variable (IV) estimators to estimate unbiased economies of scale. At
      the programme level, we find that, after controlling for the endogeneity of
      scale, the scale-up of Avahan has generated high economies of scale. Our findings
      suggest that average cost reductions per person reached are achievable when
      scaling-up HIV prevention in low and middle income countries. 

PMID- 25779622
TI  - Traditional acupuncturists and higher education in Britain: the dual, paradoxical
      impact of biomedical alignment on the holistic view.
AB  - Traditional acupuncturists' quest for external legitimacy in Britain involves the
      standardization of their knowledge bases through the development of training
      schools and syllabi, formal educational structures, and, since the 1990s, the
      teaching of undergraduate courses within (or validated by) Higher Education
      Institutions (HEIs), a process which entails biomedical alignment of the
      curriculum. However, as holistic discourses were commonly used as a rhetorical
      strategy by CAM practitioners to distance themselves from biomedicine and as a
      source of public appeal, this 'mainstreaming' process evoked practitioners'
      concerns that their holistic claims are being compromised. An additional
      challenge is being posed by a group of academics and scientists in Britain who
      launched an attack on CAM courses taught in HEIs, accusing them of being
      'unscientific' and 'non-academic' in nature. This paper explores the negotiation
      of all these challenges during the formalization of traditional acupuncture
      education in Britain, with a particular focus on the role of HEIs. The in-depth
      qualitative investigation draws on several data sets: participant observation in
      a university validated acupuncture course; in-depth interviews; and documentary
      analysis. The findings show how, as part of the formalization process,
      acupuncturists in Britain (re)negotiate their holistic, anti-reductionist
      discourses and claims in relation to contemporary societal, political and
      cultural forces. Moreover, the teaching and validation of acupuncture courses by
      HEIs may contribute to broadening acupuncturists' 'holistic awareness' of
      societal and cultural influences on individuals' and communities' ill-health.
      This investigation emphasises the dynamic and context-specific (rather than fixed
      and essentialized) nature of acupuncture practice and knowledge. 

PMID- 25779623
TI  - Reliability of the 36-item version of the Token Test in patients with poststroke
      aphasia.
AB  - AIM: The purpose of this study was to investigate the intra- and inter-rater
      reliability of the 36-item version of the Token Test. METHODS: Twenty-four people
      following stroke with mild disorder of language comprehension were assessed by
      two speech therapists at a distance of 2  days apart. RESULTS: The test showed
      excellent and good inter-rater reliability, while some parts had lower
      coefficients. CONCLUSION: This version of the Token Test can be used to assess
      mild disorder of oral language comprehension. However, further clearer
      instructions for administration and scoring may improve the test reliability.

PMID- 25779624
TI  - The Usefulness of Captive Kept Capercaillie (Tetrao urogallus L.) as the Semen
      Donors for Artificial Insemination and Gene Pool Preservation In vitro.
AB  - Captive breeding of birds threatened by extinction in zoological gardens or other
      closed aviary centres is one of the methods allowing their protection and gene
      pool preservation ex situ in vivo. Such birds are usually kept in captivity
      lifelong and serve as parents of several new generations that can be further
      released into natural environment, or males are used as semen donors for
      artificial insemination and gene banking. Therefore, the fecundity of such flocks
      (number of laid egg and spermatozoa quantity and quality) is very important. The
      aim of this study was to evaluate the usefulness of captive kept capercaillie
      (Tetrao urogallus L.) as semen donors in three subsequent reproductive seasons,
      based on the assessment of manually collected semen quality. Male response to
      dorso-abdominal massage, ejaculate volume, sperm concentration, motility and
      morphology were evaluated individually at three succeeding years. Depending on
      individual male properties and year of collection, the number of positive
      reactions to semen collection attempts (i.e. ending with ejaculation) varied from
      44.4% to 100.0%; single ejaculate volume ranged from 10 to 300 MUl, spermatozoa
      concentration from 10 * 10(6) per ml to 3520 * 10(6) per ml and percentage of
      live morphologically normal spermatozoa from 19.3 to 80.3%. The highest average
      value (66.7) of semen quality factor (SQF) was noted for a 2-year-old male
      (varying from 1.9 to 258.1), while the lowest for ten- (4.8; varying from 0.1 to
      17.0) and 7-year-old (6.6; varying between 0.6 and 13.6). Assuming that for AI
      purposes, the ejaculate quality has to be at minimum 10 SQF, obtained results
      indicate that majority of capercaillie kept in captivity, both young (2-3 years
      old) and older (up to 10 years old), can be valuable semen producers in
      succeeding seasons. 

PMID- 25779625
TI  - Indications and expectations for neuropsychological assessment in routine
      epilepsy care: Report of the ILAE Neuropsychology Task Force, Diagnostic Methods
      Commission, 2013-2017.
AB  - The International League Against Epilepsy (ILAE) Diagnostic Methods Commission
      charged the Neuropsychology Task Force with the job of developing a set of
      recommendations to address the following questions: (1) What is the role of a
      neuropsychological assessment? (2) Who should do a neuropsychological assessment?
      (3) When should people with epilepsy be referred for a neuropsychological
      assessment? and (4) What should be expected from a neuropsychological assessment?
      The recommendations have been broadly written for health care clinicians in
      established epilepsy settings as well as those setting up new services. They are
      based on a detailed survey of neuropsychological assessment practices across
      international epilepsy centers, and formal ranking of specific recommendations
      for advancing clinical epilepsy care generated by specialist epilepsy
      neuropsychologists from around the world. They also incorporate the latest
      research findings to establish minimum standards for training and practice,
      reflecting the many roles of neuropsychological assessment in the routine care of
      children and adults with epilepsy. The recommendations endorse routine screening
      of cognition, mood, and behavior in new-onset epilepsy, and describe the range of
      situations when more detailed, formal neuropsychological assessment is indicated.
      They identify a core set of cognitive and psychological domains that should be
      assessed to provide an objective account of an individual's cognitive, emotional,
      and psychosocial functioning, including factors likely contributing to deficits
      identified on qualitative and quantitative examination. The recommendations also
      endorse routine provision of feedback to patients, families, and clinicians about
      the implications of the assessment results, including specific clinical
      recommendations of what can be done to improve a patient's cognitive or
      psychosocial functioning and alleviate the distress of any difficulties
      identified. By canvassing the breadth and depth of scope of neuropsychological
      assessment, this report demonstrates the pivotal role played by this noninvasive
      and minimally resource intensive investigation in the care of people with
      epilepsy. 

PMID- 25779626
TI  - Gene expression demonstrates an immunological capacity of the human endolymphatic
      sac.
AB  - OBJECTIVES/HYPOTHESIS: The purpose of the present study is to explore,
      demonstrate, and describe the expression of genes related to the innate immune
      system in the human endolymphatic sac. It is hypothesized that the endolymphatic
      sac has a significant immunological function in the human inner ear. STUDY
      DESIGN: DNA microarrays and immunohistochemistry were used for analyses of fresh
      human endolymphatic-sac tissue samples. METHODS: Twelve tissue samples from the
      human endolymphatic sac were obtained during translabyrinthine surgery for
      vestibular schwannoma. Microarray technology was used to investigate tissue
      sample gene expression using adjacent dura mater as control. The expression of
      genes specific for the innate immune system was determined and results for
      selected key molecules verified by immunohistochemistry. RESULTS: A comprehensive
      overview of expressed genes of the innate immune system was obtained. Multiple
      key elements of both the cellular and humoral innate immune system were
      expressed, including Toll-like receptors 4 and 7, as well as beta-defensin and
      lactoferrin. CONCLUSIONS: The present data provides the first direct evidence of
      an immunological capacity of the human endolymphatic sac. At the molecular level,
      the endolymphatic sac is capable of antigen recognition and processing for
      initiation of an immune response. In addition, potent molecules directly toxic to
      invading pathogens are expressed by the sac epithelium. This evidence strongly
      supports the endolymphatic sac as a significant immunological entity of the inner
      ear. LEVEL OF EVIDENCE: N/A.

PMID- 25779627
TI  - Enhanced automated sleep spindle detection algorithm based on synchrosqueezing.
AB  - Detection of sleep spindles is of major importance in the field of sleep
      research. However, manual scoring of spindles on prolonged recordings is very
      laborious and time-consuming. In this paper, we introduce a new algorithm based
      on synchrosqueezing transform for detection of sleep spindles. Synchrosqueezing
      is a powerful time-frequency analysis tool that provides precise frequency
      representation of a multicomponent signal through mode decomposition.
      Subsequently, the proposed algorithm extracts and compares the basic features of
      a spindle-like activity with its surrounding, thus adapting to an expert's visual
      criteria for spindle scoring. The performance of the algorithm was assessed
      against the spindle scoring of one expert on continuous electroencephalogram
      sleep recordings from two subjects. Through appropriate choice of
      synchrosqueezing parameters, our proposed algorithm obtained a maximum
      sensitivity of 96.5% with 98.1% specificity. Compared to previously published
      works, our algorithm has shown improved performance by enhancing the quality of
      sleep spindle detection.

PMID- 25779628
TI  - Generation of transgenic fibroblasts producing doxycycline-inducible human
      interferon-alpha or erythropoietin for a bovine mammary bioreactor.
AB  - Interferon alpha (IFN-alpha) is a cytokine, produced predominantly in immune
      cells in response to pathogens, which interferes with viral replication in host
      cells. Another cytokine hormone, erythropoietin (EPO), is synthesized in
      interstitial fibroblasts of the kidney and acts as a stimulator for the
      production of red blood cells. Importantly, the two cytokines have been used in
      the treatment of certain hematological malignancies, including renal anemia. In
      the production of recombinant proteins, a transgenic expression system in bovine
      species is an efficient strategy for pharmaceutical production. In the present
      study, recombinant constructs capable of producing recombinant human IFN-alpha
      and EPO proteins were established and were generated containing the mammary gland
      specific alphaS1-casein promoter region (between -175 and + 796 nt), as this
      promoter was revealed to have the highest level of activity in a previous
      promoter study. In order to minimize developmental toxicity by constitutive
      exogenous expression, a doxycycline (dox)-inducible system was introduced to the
      IFN-alpha/EPO-expressing constructs. Therefore, a unitary tetracycline (tet)-on
      the IFN-alpha/EPO vector was established, which combined a tet-on activator
      cassette controlled by the alphaS1-casein promoter, with a responder cassette
      encoding the IFN-alpha/EPO gene, controlled by the tetracycline response element
      (TRE) promoter. In these systems, the tet-controlled transactivator is affected
      by mammary gland-specific alphaS1-casein promoter, and binding of the
      transcriptional activator to the TRE results in transcription of the downstream
      IFN-alpha/EPO genes in the presence of dox. To assess this, the unitary tet-on
      IFN-alpha/EPO vector was introduced into a bovine mammary gland cell line (MAC
      T), and the cells were then treated with 0.1-1 ug/ml dox. A marked increase was
      observed in the expression levels of IFN-alpha/EPO. In addition, bovine
      transgenic fibroblasts containing a mammary gland-specific and dox-inducible IFN
      alpha/EPO construct were generated. These transgenic fibroblasts may provide a
      source for somatic cell nuclear transfer for the generation of transgenic cattle
      producing recombinant human IFN-alpha/EPO protein during lactation.

PMID- 25779630
TI  - High morale is associated with increased survival in the very old.
AB  - BACKGROUND: high morale is defined as future-oriented optimism. Previous research
      suggests that a high morale independently predicts increased survival among old
      people, though very old people have not been specifically studied. OBJECTIVE: to
      investigate whether high morale is associated with increased survival among very
      old people. SUBJECTS: the Umea 85+/GErontological Regional DAtabase-study (GERDA)
      recruited participants aged 85 years and older in northern Sweden and western
      Finland during 2000-02 and 2005-07, of whom 646 were included in this study.
      METHODS: demographic, functional- and health-related data were collected in this
      population-based study through structured interviews and assessments carried out
      during home visits and from reviews of medical records. The 17-item Philadelphia
      Geriatric Center Morale Scale (PGCMS) was used to assess morale. RESULTS: the 5
      year survival rate was 31.9% for participants with low morale, 39.4% for moderate
      and 55.6% for those with high morale. In an unadjusted Cox model, the relative
      risk (RR) of mortality was higher among participants with low morale (RR = 1.86,
      P < 0.001) and moderate morale (RR = 1.59, P < 0.001) compared with participants
      with high morale. Similar results were found after adjustment for age and gender.
      In a Cox model adjusted for several demographic, health- and function-related
      confounders, including age and gender, mortality was higher among participants
      with low morale (RR = 1.36, P = 0.032) than those with high morale. There was a
      similar but non-significant pattern towards increased mortality in participants
      with moderate morale (RR = 1.21, P value = 0.136). CONCLUSION: high morale is
      independently associated with increased survival among very old people.

PMID- 25779629
TI  - Mitochondrial superoxide in osteocytes perturbs canalicular networks in the
      setting of age-related osteoporosis.
AB  - Osteocytes are major bone cells that play a crucial role in maintaining the
      quality of and healing damage to bone tissue. The number of living osteocytes and
      canalicular networks declines in an age-dependent manner. However, the
      pathological effects of mitochondrial redox imbalances on osteocytes and bone
      metabolism have not been fully elucidated. We generated mice lacking
      mitochondrial superoxide dismutase 2 (Sod2) in osteocytes. Like an aged bone,
      Sod2 depletion in the osteocytes positively enhanced the production of cellular
      superoxide in vivo. A bone morphological analysis demonstrated that the Sod2
      deficient femurs showed remarkable bone loss in an age-dependent manner.
      Interestingly, Sod2 loss induced markedly disorganized osteocytic canalicular
      networks and decreased the number of live osteocytes. Furthermore, Sod2
      deficiency significantly suppressed bone formation and increased bone resorption
      concomitant with the upregulation of sclerostin and receptor activator of NF
      kappaB ligand (RANKL). In vitro experiments also revealed that treatment with
      paraquat, a superoxide inducer in mitochondria, promoted the RANKL expression
      via, in part, ERK phosphorylation. These findings demonstrate that the
      mitochondrial superoxide induced in osteocytes by Sod2 ablation causes age
      related bone loss due to the impairment of canalicular networks and bone
      metabolism via the deregulation of the sclerostin and RANKL expression. 

PMID- 25779631
TI  - Red and far-red fluorescent dyes for the characterization of head and neck cancer
      at the cellular level.
AB  - BACKGROUND: Primary upper aerodigestive tract malignancy remains a cancer having
      a poor prognosis, despite current progress in treatment, due to a generally late
      diagnosis. OBJECTIVES: We conducted a preliminary assessment of five dyes
      approved for human use for the imaging of head and neck tissues at the cellular
      level, which could be considered for clinical examination. METHODS: We
      investigated fluorescence endomicroscopic images on fresh samples obtained from
      head and neck surgeries after staining with hypericin, methylene blue, toluidine
      blue, patent blue or indocyanine green to provide a preliminary consideration as
      to whether these images contain enough information for identification of non
      pathologic and pathologic tissues. The distribution pattern of dye has been
      examined using probe-based confocal laser endomicroscopy (pCLE) in ex vivo
      specimens and compared with corresponding histology. RESULTS: In most samples,
      the image quality provided by pCLE with both dyes allowed pathologists to
      recognize histological characteristics to identify the tissues. CONCLUSION: The
      combination of pCLE imaging with these dyes provides interpretable images close
      to conventional histology; a promising clinical tool to assist physicians in
      examination of upper aerodigestive tract, as long as depth imaging issues can be
      overcome.

PMID- 25779632
TI  - Infiltration of circulating myeloid cells through CD95L contributes to
      neurodegeneration in mice.
AB  - Neuroinflammation is increasingly recognized as a hallmark of neurodegeneration.
      Activated central nervous system-resident microglia and infiltrating immune cells
      contribute to the degeneration of dopaminergic neurons (DNs). However, how the
      inflammatory process leads to neuron loss and whether blocking this response
      would be beneficial to disease progression remains largely unknown. CD95 is a
      mediator of inflammation that has also been proposed as an apoptosis inducer in
      DNs, but previous studies using ubiquitous deletion of CD95 or CD95L in mouse
      models of neurodegeneration have generated conflicting results. Here we examine
      the role of CD95 in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridin (MPTP)-induced
      neurodegeneration using tissue-specific deletion of CD95 or CD95L. We show that
      DN death is not mediated by CD95-induced apoptosis because deletion of CD95 in
      DNs does not influence MPTP-induced neurodegeneration. In contrast, deletion of
      CD95L in peripheral myeloid cells significantly protects against MPTP
      neurotoxicity and preserves striatal dopamine levels. Systemic pharmacological
      inhibition of CD95L dampens the peripheral innate response, reduces the
      accumulation of infiltrating myeloid cells, and efficiently prevents MPTP-induced
      DN death. Altogether, this study emphasizes the role of the peripheral innate
      immune response in neurodegeneration and identifies CD95 as potential
      pharmacological target for neurodegenerative disease. 

PMID- 25779633
TI  - Inefficient clearance of myelin debris by microglia impairs remyelinating
      processes.
AB  - An imbalance between remyelinating and demyelinating rates underlies degenerative
      processes in demyelinating diseases such as multiple sclerosis. An optimal
      therapeutic strategy would be to stimulate remyelination while limiting
      demyelination. Although accumulation of myelin debris impairs remyelination, the
      mechanisms regulating the clearance of such debris by mononuclear phagocytic
      cells are poorly understood. We demonstrate that after cuprizone intoxication,
      CCR2-dependent infiltration of mouse bone marrow-derived cells is abundant in
      demyelinating areas, but that these cells do not impact demyelination. However,
      in CX3CR1-deficient mice, the clearance of myelin debris by microglia was blocked
      greatly, affecting the integrity of the axon and myelin sheaths and thus
      preventing proper remyelination. These results highlight the crucial role played
      by CX3CR1 in myelin removal and show that there can be no efficient remyelination
      after a primary demyelinating insult if myelin clearance by microglia is
      impaired. 

PMID- 25779635
TI  - Under-reporting and case fatality estimates for emerging epidemics.

PMID- 25779634
TI  - IgE-activated basophils regulate eosinophil tissue entry by modulating
      endothelial function.
AB  - Vertebrate immunity has evolved a modular architecture in response to
      perturbations. Allergic inflammation represents such a module, with signature
      features of antigen-specific IgE and tissue eosinophilia, although the cellular
      and molecular circuitry coupling these responses remains unclear. Here, we use
      genetic and imaging approaches in models of IgE-dependent eosinophilic dermatitis
      to demonstrate a requisite role for basophils. After antigenic inflammation,
      basophils initiate transmigration like other granulocytes but, upon activation
      via their high-affinity IgE receptor, alter their migratory kinetics to persist
      at the endothelium. Prolonged basophil-endothelial interactions, in part
      dependent on activation of focal adhesion kinases, promote delivery of basophil
      derived IL-4 to the endothelium and subsequent induction of endothelial vascular
      cell adhesion molecule-1 (VCAM-1), which is required for eosinophil accumulation.
      Thus, basophils are gatekeepers that link adaptive immunity with innate effector
      programs by altering access to tissue sites by activation-induced interactions
      with the endothelium. 

PMID- 25779636
TI  - Randomized crossover trial of endotracheal tube suctioning systems use in
      newborns.
AB  - BACKGROUND: Maintaining endotracheal tube patency is critical for neonates
      receiving mechanical ventilation. Endotracheal tube suctioning removes
      accumulated secretions preventing potential adverse events, however is also
      potentially hazardous to the patient. OBJECTIVE: To compare respiratory rate,
      arterial blood oxygen saturation, heart rate and pain in newborns undergoing
      endotracheal tube suctioning with closed (CS) and open (OS) systems. METHODS:
      Randomized crossover trial with 13 newborns from two Brazilian hospitals. The
      respiratory rate, arterial blood oxygen saturation, heart rate and pain
      (Premature Infant Pain Profile) were analysed: immediately before (T1), during
      (T2), immediately after (T3), 10 min after (T4) and 30 min (T5) after
      endotracheal suctioning. RESULTS: The majority (11/85.0%) of the newborns were
      premature and 45% weighed less than 1000 g. No statistically significant
      difference was identified according to the use of CS or OS to all the parameters
      investigated. The main results demonstrated that in T2 arterial blood oxygen
      saturation was higher with CS (CS 93.0%; OS 89 . 0%; p = 0.561). In T3 there was
      an increase in respiratory rate average only with the use of OS (T1 50.0; T3
      56.0). The pain score in T2 and heart rate in T3 were higher with OS without
      significant differences (p = 0.114; p = 0.479, respectively). CONCLUSION: There
      was no significant difference in the studied clinical parameters or presence and
      intensity of pain according to the two investigated techniques of endotracheal
      tube suctioning. RELEVANCE TO CLINICAL PRACTICE: This research can provide
      support for clinical practice regarding endotracheal tube suctioning of newborns
      describing that the use of closed systems was similar to the open system
      regarding pain presence and intensity, as well as, in the clinical effects
      analysed, in accordance with other studies produced in this field.

PMID- 25779637
TI  - Inflammatory microenvironment and tumor necrosis factor alpha as modulators of
      periostin and CCN2 expression in human non-healing skin wounds and dermal
      fibroblasts.
AB  - Non-healing skin wounds remain a significant clinical burden, and in recent
      years, the regulatory role of matricellular proteins in skin healing has received
      significant attention. Periostin and CCN2 are both upregulated at day 3 post
      wounding in murine skin, where they regulate aspects of the proliferative phase
      of repair including mesenchymal cell infiltration and myofibroblast
      differentiation. In this study, we examined 1) the wound phenotype and expression
      patterns of periostin and CCN2 in non-healing skin wounds in humans and 2) the
      regulation of their expression in wound fibroblasts by tumor necrosis factor
      alpha (TNFalpha) and transforming growth factor-beta1 (TGF-beta1). Chronic skin
      wounds had a pro-inflammatory phenotype, characterized by macrophage
      infiltration, TNFalpha immunoreactivity, and neutrophil infiltration. Periostin,
      but not CCN2, was significantly suppressed in non-healing wound edge tissue at
      the mRNA and protein level compared with non-involved skin. In vitro, human wound
      edge fibroblasts populations were still able to proliferate and contract collagen
      gels. Compared to cells from non-involved skin, periostin and alpha-SMA mRNA
      levels increased significantly in the presence of TGF-beta1 in wound cells and
      were significantly decreased by TNFalpha, but not those of Col1A2 or CCN2. In the
      presence of both TGF-beta1 and TNFalpha, periostin and alpha-SMA mRNA levels were
      significantly reduced compared to TGF-beta1 treated wound cells. Effects of TGF
      beta1 and TNFalpha on gene expression were also more pronounced in wound edge
      cells compared to non-involved fibroblasts. We conclude that variations in the
      expression of periostin and CCN2, are related to an inflammatory microenvironment
      and the presence of TNFalpha in human chronic wounds. 

PMID- 25779638
TI  - A Plant-Derived Multi-HIV Antigen Induces Broad Immune Responses in Orally
      Immunized Mice.
AB  - Multi-HIV, a multiepitopic protein derived from both gp120 and gp41 envelope
      proteins of the human immunodeficiency virus (HIV), has been proposed as a
      vaccine prototype capable of inducing broad immune responses, as it carries
      various B and T cell epitopes from several HIV strains. In this study, the
      immunogenic properties of a Multi-HIV expressed in tobacco chloroplasts are
      evaluated in test mice. BALB/c mice orally immunized with tobacco-derived Multi
      HIV have elicited antibody responses, including both the V3 loop of gp120 and the
      ELDKWA epitope of gp41. Based on splenocyte proliferation assays, stimulation
      with epitopes of the C4, V3 domain of gp120, and the ELDKWA domain of gp41
      elicits positive cellular responses. Furthermore, specific interferon gamma
      production is observed in both CD4+ and CD8+ T cells stimulated with HIV
      peptides. These results demonstrate that plant-derived Multi-HIV induces T helper
      specific responses. Altogether, these findings illustrate the immunogenic
      potential of plant-derived Multi-HIV in an oral immunization scheme. The
      potential of this low-cost immunization approach and its implications on HIV/AIDS
      vaccine development are discussed.

PMID- 25779639
TI  - Recombinant Bacillus subtilis Spores Elicit Th1/Th17-Polarized Immune Response in
      a Murine Model of Helicobacter pylori Vaccination.
AB  - Current progress in research on vaccines against Helicobacter pylori emphasizes
      the significance of eliciting the Th1/Th17-polarized immune response. Such
      polarization can be achieved by selection of appropriate antigen and adjuvant. In
      this study, we wanted to check the polarization of the immune response elicited
      by UreB protein of Helicobacter acinonychis delivered by recombinant Bacillus
      subtilis spores upon oral immunization. B. subtilis spores presenting fragment of
      UreB protein and able to express entire UreB in vegetative cells after
      germination were orally administered to mice along with aluminum hydroxide or
      recombinant spores presenting IL-2 as an adjuvant. The pattern of cytokines
      secreted by sensitized splenocytes assessed by the cytometric bead array clearly
      indicated polarization of the immune response toward both Th1 and Th17 in mice
      immunized with the use of above-mentioned adjuvants. Obtained result is promising
      regarding the usage of recombinant spores in formulations of vaccines against H.
      pylori and line up with the current state of research emphasizing the key role of
      appropriate adjuvants. 

PMID- 25779640
TI  - Cloning of Toluene 4-Monooxygenase Genes and Application of Two-Phase System to
      the Production of the Anticancer Agent, Indirubin.
AB  - Indirubin is a strong inhibitor of several eukaryotic cell signaling pathways and
      shows promise as a treatment for myelocytic leukemia and Alzheimer's disease. The
      tmoABCDEF operon, encoding the components of a novel toluene 4-monooxygenase from
      the paint factory soil isolate, Pseudomonas sp. M4, was cloned and expressed in
      Escherichia coli. E. coli::pKSR12 expressing the tmo genes was used to develop a
      two-phase [dioctyl phthalate (DOP)/aqueous medium] culture system that was
      optimized to obtain maximal yields of indirubin from the starting substrate,
      indole. DOP was used as the organic phase to solubilize and sequester the toxic
      indole substrate, making possible the use of high indole concentrations that
      would otherwise interfere with growth in aqueous media. A 50 % (v/v) DOP two
      phase system using tryptophan medium containing 3 mM cysteine, 5 mM indole, and 1
      mM isatin yielded 102.4 mg/L of indirubin with no conversion of indole to the
      less valuable alternate product, indigo.

PMID- 25779641
TI  - C/EBPbeta (CEBPB) protein binding to the C/EBP|CRE DNA 8-mer TTGC|GTCA is
      inhibited by 5hmC and enhanced by 5mC, 5fC, and 5caC in the CG dinucleotide.
AB  - During mammalian development, some methylated cytosines (5mC) in CG dinucleotides
      are iteratively oxidized by TET dioxygenases to 5-hydroxymethylcytosine (5hmC), 5
      formylcytosine (5fC), and 5-carboxylcytosine (5caC). The effect of these cytosine
      oxidative products on the sequence-specific DNA binding of transcription factors
      is being actively investigated. Here, we used the electrophoretic mobility shift
      assay (EMSA) to examine C/EBPalpha and C/EBPbeta homodimers binding to all 25
      chemical forms of a CG dinucleotide for two DNA sequences: the canonical C/EBP 8
      mer TTGC|GCAA and the chimeric C/EBP|CRE 8-mer TTGC|GTCA. 5hmC in the CG
      dinucleotide in the C/EBP|CRE motif 8-mer TGAC|GCAA inhibits binding of C/EBPbeta
      but not C/EBPalpha. Binding was increased by 5mC, 5fC and 5caC. Circular
      dichroism monitored thermal denaturations for C/EBPbeta bound to the C/EBP|CRE
      motif confirmed the EMSA. The structural differences between C/EBPalpha and
      C/EBPbeta that may account for the difference in binding 5hmC in the 8-mer
      TGAC|GCAA are explored. 

PMID- 25779642
TI  - Homology modeling and virtual screening of inhibitors against TEM- and SHV-type
      resistant mutants: A multilayer filtering approach.
AB  - TEM and SHV are class-A-type beta-lactamases commonly found in Escherichia coli
      and Klebsiella pneumoniae. Previous studies reported S130G and K234R mutations in
      SHVs to be 41- and 10-fold more resistant toward clavulanic acid than SHV-1,
      respectively, whereas TEM S130G and R244S also showed the same level of
      resistance. These selected mutants confer higher level of resistance against
      clavulanic acid. They also show little susceptibility against other commercially
      available beta-lactamase inhibitors. In this study, we have used docking-based
      virtual screening approach in order to screen potential inhibitors against some
      of the major resistant mutants of SHV and TEM types beta-lactamase. Two different
      inhibitor-resistant mutants from SHV and TEM were selected. Moreover, we have
      retained the active site water molecules within each enzyme. Active site water
      molecules were placed within modeled structure of the mutant whose structure was
      unavailable with protein databank. The novelty of this work lies in the use of
      multilayer virtual screening approach for the prediction of best and accurate
      results. We are reporting five inhibitors on the basis of their efficacy against
      all the selected resistant mutants. These inhibitors were selected on the basis
      of their binding efficacies and pharmacophore features. 

PMID- 25779643
TI  - Trichosanthes kirilowii fruits inhibit non-small cell lung cancer cell growth
      through mitotic cell-cycle arrest.
AB  - Lung cancer is the leading cause of cancer-related death worldwide. Non-small
      cell lung cancer (NSCLC) accounts for 80% of lung cancer cases and the reported
      overall 5-year survival rate is less than 5%. Natural medicines have attracted
      much attention due to their lower toxicity and fewer side effects. Trichosanthes
      kirilowii Maxim (TKM) fruits are commonly used in cancer treatment in combination
      with other Chinese medicinal herbs. However, little is known about their
      biological functions and mechanisms in NSCLC cells. In this study, we
      investigated the efficacy of TKM fruits in NSCLC cells using cell proliferation,
      invasion, migration, and anchorage independent assays and a Xenograft NSCLC tumor
      model, and explored the possible biological mechanism by flow cytometric
      analysis, cDNA microarray and real-time PCR. Results showed that TKM fruits
      significantly suppressed NSCLC cell proliferation, migration, invasion,
      tumorigenicity and tumor growth, and significantly extended the survival time of
      NSCLC-bearing mice. Flow cytometric analysis showed that TKM fruits significantly
      induced G2-M arrest, necrosis and apoptosis in NSCLC cells. cDNA microarray
      analysis revealed that TKM fruits regulated the differential expression of 544
      genes, and the differential expression of selected genes was also confirmed. Gene
      ontology (GO) analysis showed that 18 of first 20 biological processes were
      involved in cell cycle and mitosis. These results indicate that TKM fruits have
      certain inhibitory effect on NSCLC cells through cell-cycle and mitosis arrest,
      and suggest that TKM fruits may be an important resource for developing new
      antitumor drugs, and a potent natural product for treating patients with NSCLC.

PMID- 25779644
TI  - Kaempferol induces DNA damage and inhibits DNA repair associated protein
      expressions in human promyelocytic leukemia HL-60 cells.
AB  - Numerous evidences have shown that plant flavonoids (naturally occurring
      substances) have been reported to have chemopreventive activities and protect
      against experimental carcinogenesis. Kaempferol, one of the flavonoids, is widely
      distributed in fruits and vegetables, and may have cancer chemopreventive
      properties. However, the precise underlying mechanism regarding induced DNA
      damage and suppressed DNA repair system are poorly understood. In this study, we
      investigated whether kaempferol induced DNA damage and affected DNA repair
      associated protein expression in human leukemia HL-60 cells in vitro. Percentages
      of viable cells were measured via a flow cytometry assay. DNA damage was examined
      by Comet assay and DAPI staining. DNA fragmentation (ladder) was examined by DNA
      gel electrophoresis. The changes of protein levels associated with DNA repair
      were examined by Western blotting. Results showed that kaempferol dose
      dependently decreased the viable cells. Comet assay indicated that kaempferol
      induced DNA damage (Comet tail) in a dose-dependent manner and DAPI staining also
      showed increased doses of kaempferol which led to increased DNA condensation,
      these effects are all of dose-dependent manners. Western blotting indicated that
      kaempferol-decreased protein expression associated with DNA repair system, such
      as phosphate-ataxia-telangiectasia mutated (p-ATM), phosphate-ataxia
      telangiectasia and Rad3-related (p-ATR), 14-3-3 proteins sigma (14-3-3sigma), DNA
      dependent serine/threonine protein kinase (DNA-PK), O(6)-methylguanine-DNA
      methyltransferase (MGMT), p53 and MDC1 protein expressions, but increased the
      protein expression of p-p53 and p-H2AX. Protein translocation was examined by
      confocal laser microscopy, and we found that kaempferol increased the levels of p
      H2AX and p-p53 in HL-60 cells. Taken together, in the present study, we found
      that kaempferol induced DNA damage and suppressed DNA repair and inhibited DNA
      repair associated protein expression in HL-60 cells, which may be the factors for
      kaempferol induced cell death in vitro.

PMID- 25779645
TI  - Chrysanthemum promotes adipocyte differentiation, adiponectin secretion and
      glucose uptake.
AB  - The adipose tissue is an endocrine organ, and its endocrine function is closely
      related to type 2 diabetes. Edible Chrysanthemum morifolium Ramat. (ECM)
      possesses several biological properties; however, its effect on adipocytes
      remains unclear. We investigated the effect of the hot water extract of ECM (HW
      ECM) on 3T3-L1 adipocytes. HW-ECM enhanced adipocyte differentiation, adiponectin
      secretion, and glucose uptake in 3T3-L1 cells. It also increased the mRNA levels
      of peroxisome proliferator-activated receptor gamma (PPARgamma), a regulator of
      adipocyte differentiation, adiponectin transcription, and GLUT4 expression. In
      addition, HW-ECM increased the mRNA levels of CCAAT/enhancer-binding protein
      delta (C/EBPdelta), which induces PPARgamma expression, but not C/EBPbeta, during
      early adipocyte differentiation. These results suggest that HW-ECM enhances
      adipocyte differentiation, adiponectin secretion, and glucose uptake through
      C/EBPdelta-induced PPARgamma expression. These effects of HW-ECM on adipocytes
      suggest that HW-ECM is potentially beneficial for type 2 diabetes.

PMID- 25779646
TI  - Novel steps in the autophagic-lysosomal pathway.
AB  - Autophagy is the process by which portions of cytoplasm are enclosed by
      membranous organelles, phagophores, which deliver the sequestered cytoplasm to
      degradative autophagic vacuoles. Genes and proteins involved in phagophore
      manufacture have been extensively studied, but little is known about how mature
      phagophores proceed through the subsequent steps of expansion, closure and
      fusion. Here we have addressed these issues by combining our unique autophagic
      cargo sequestration assay (using the cytosolic enzyme lactate dehydrogenase as a
      cargo marker) with quantitative measurements of the lipidation-dependent
      anchorage and turnover of the phagophore-associated protein LC3. In isolated rat
      hepatocytes, amino acid starved to induce maximal autophagic activity, the two
      unrelated reversible autophagy inhibitors 3-methyladenine (3MA) and thapsigargin
      (TG) both blocked cargo sequestration completely. However, whereas 3MA inhibited
      LC3 lipidation, TG did not, thus apparently acting at a post-lipidation step to
      prevent phagophore closure. Intriguingly, the resumption of cargo sequestration
      seen upon release from a reversible TG block was completely suppressed by 3MA,
      revealing that 3MA not only inhibits LC3 lipidation but also (like TG) blocks
      phagophore closure at a post-lipidation step. 3MA did not, however, prevent the
      resumption of lysosomal LC3 degradation, indicating that phagophores could fuse
      directly with degradative autophagic vacuoles without carrying cytosolic cargo.
      This fusion step was clearly blocked by TG. Furthermore, density gradient
      centrifugation revealed that a fraction of the LC3-marked phagophores retained by
      TG could be density-shifted by the acidotropic drug propylamine along with the
      lysosomal marker cathepsin B, suggesting physical association of some phagophores
      with lysosomes prior to cargo sequestration.

PMID- 25779647
TI  - The design of 3D scaffold for tissue engineering using automated scaffold design
      algorithm.
AB  - Several progresses have been introduced in the field of bone regenerative
      medicine. A new term tissue engineering (TE) was created. In TE, a highly porous
      artificial extracellular matrix or scaffold is required to accommodate cells and
      guide their growth in three dimensions. The design of scaffolds with desirable
      internal and external structure represents a challenge for TE. In this paper, we
      introduce a new method known as automated scaffold design (ASD) for designing a
      3D scaffold with a minimum mismatches for its geometrical parameters. The method
      makes use of k-means clustering algorithm to separate the different tissues and
      hence decodes the defected bone portions. The segmented portions of different
      slices are registered to construct the 3D volume for the data. It also uses an
      isosurface rendering technique for 3D visualization of the scaffold and bones. It
      provides the ability to visualize the transplanted as well as the normal bone
      portions. The proposed system proves good performance in both the segmentation
      results and visualizations aspects. 

PMID- 25779648
TI  - Accuracy of Image-Fusion Stereolithographic Guides: Mapping CT Data with Three
      Dimensional Optical Surface Scanning.
AB  - BACKGROUND: Computer-assisted implant surgery usually requires a radiographic
      scan template as the basis for prosthetic-driven implant planning and surgical
      guide fabrication. PURPOSE: The study aims to evaluate the accuracy of image
      fusion stereolithographic guides in which a computed tomography (CT) scan is
      mapped with three-dimensional optical scans of cast and diagnostic wax-up.
      MATERIALS AND METHODS: Three-dimensional error at the base and tip of the
      implants, angular deviation of the implant-axis, and the inserting-depth error of
      120 implants with a length of 10 mm and a caliber of 4.1 mm in 15 polymer-models
      were examined. A control CT was performed and fused with the planning data for
      accuracy evaluation. RESULTS: The mean three-dimensional error was 0.21 +/- 0.10
      mm (0.00-0.48 mm) at the implant base, 0.32 +/- 0.17 mm (0.03-0.75 mm) at the
      implant tip, and the mean angular error was 0.85 +/- 0.59 degrees  (0.00-2.50
      degrees ). The mean depth error was 0.07 +/- 0.07 mm (0.00-0.32 mm). CONCLUSIONS:
      Within the limitations of an in vitro study, the novel technique showed excellent
      accuracy. Errors from fabrication and scanning of a radiographic scan template
      can be avoided, and the workflow and costs of computer-assisted implant surgery
      may be reduced.

PMID- 25779649
TI  - Denise Barlow: a career in epigenetics.

PMID- 25779650
TI  - Self-assembly of a dual functional bioactive peptide amphiphile incorporating
      both matrix metalloprotease substrate and cell adhesion motifs.
AB  - We describe a bioactive lipopeptide that combines the capacity to promote the
      adhesion and subsequent self-detachment of live cells, using template-cell
      environment feedback interactions. This self-assembling peptide amphiphile
      comprises a diene-containing hexadecyl lipid chain (C16e) linked to a matrix
      metalloprotease-cleavable sequence, Thr-Pro-Gly-Pro-Gln-Gly-Ile-Ala-Gly-Gln, and
      contiguous with a cell-attachment and signalling motif, Arg-Gly-Asp-Ser.
      Biophysical characterisation revealed that the PA self-assembles into 3 nm
      diameter spherical micelles above a critical aggregation concentration (cac). In
      addition, when used in solution at 5-150 nM (well below the cac), the PA is
      capable of forming film coatings that provide a stable surface for human corneal
      fibroblasts to attach and grow. Furthermore, these coatings were demonstrated to
      be sensitive to metalloproteases expressed endogenously by the attached cells,
      and consequently to elicit the controlled detachment of cells without
      compromising their viability. As such, this material constitutes a novel class of
      multi-functional coating for both fundamental and clinical applications in tissue
      engineering. 

PMID- 25779651
TI  - The Topoisomerase I Inhibitor Irinotecan and the Tyrosyl-DNA Phosphodiesterase 1
      Inhibitor Furamidine Synergistically Suppress Murine Lupus Nephritis.
AB  - OBJECTIVE: The treatment of lupus nephritis is still an unmet medical need
      requiring new therapeutic approaches. Our group found recently that irinotecan,
      an inhibitor of topoisomerase I (topo I), reversed proteinuria and prolonged
      survival in mice with advanced lupus nephritis. While irinotecan is known to
      stabilize the complex of topo I and DNA, the enzyme tyrosyl-DNA phosphodiesterase
      1 (TDP-1) functions in an opposing manner by releasing topo I from DNA.
      Therefore, we undertook this study to test whether the TDP-1 inhibitor furamidine
      has an additional effect on lupus nephritis when used in combination with
      irinotecan. METHODS: NZB/NZW mice were treated with low-dose irinotecan and
      furamidine either alone or in combination beginning at age 26 weeks. DNA
      relaxation was visualized using gel electrophoresis. Binding of anti-double
      stranded DNA (anti-dsDNA) antibodies to DNA modified by topo I, TDP-1, and the
      topo I inhibitor camptothecin was determined by enzyme-linked immunosorbent
      assay. RESULTS: Compared to treatment with either agent alone, simultaneous
      treatment with low-dose irinotecan and furamidine significantly improved survival
      of NZB/NZW mice. Similar to what has been previously shown for irinotecan alone,
      the combination treatment did not change the levels of anti-dsDNA antibodies. In
      vitro, recombinant TDP-1 increased topo I-mediated DNA relaxation, resulting in
      enhanced binding of anti-dsDNA antibodies. In combination with topo I and
      camptothecin, TDP-1 reversed the inhibitory effects of camptothecin on DNA
      relaxation and anti-dsDNA binding. CONCLUSION: Affecting DNA relaxation by the
      enzymes topo I and TDP-1 and their inhibitors may be a promising approach for the
      development of new targeted therapies for systemic lupus erythematosus.

PMID- 25779652
TI  - Construction of a GeogDetector-based model system to indicate the potential
      occurrence of grasshoppers in Inner Mongolia steppe habitats.
AB  - Grasshopper plagues have seriously disturbed grassland ecosystems in Inner
      Mongolia, China. The accurate prediction of grasshopper infestations and control
      of grasshopper plagues have become urgent needs. We sampled 234, 342, 335, and
      369 plots in Xianghuangqi County of Xilingol League in 2010, 2011, 2012, and
      2013, respectively, and measured the density of the most dominant grasshopper
      species, Oedaleus decorus asiaticus, and the latitude, longitude, and associated
      relatively stable habitat factors at each plot. We used Excel-GeogDetector
      software to explore the effects of individual habitat factors and the two-factor
      interactions on grasshopper density. We estimated the membership of each
      grasshopper density rank and determined the weights of each habitat category.
      These results were used to construct a model system evaluating grasshopper
      habitat suitability. The results showed that our evaluation system was reliable
      and the fuzzy evaluation scores of grasshopper habitat suitability were good
      indicators of potential occurrence of grasshoppers. The effects of the two-factor
      interactions on grasshopper density were greater than the effects of any
      individual factors. O. d. asiaticus was most likely to be found at elevations of
      1300-1400 m, flat terrain or slopes of 4-6 degrees , typical chestnut soil with
      70-80% sand content in the top 5 cm of soil, and medium-coverage grassland. The
      species preferred temperate bunchgrass steppe dominated by Stipa krylovii and
      Cleistogenes squarrosa. These findings may be used to improve models to predict
      grasshopper occurrence and to develop management guidelines to control
      grasshopper plagues by changing habitats. 

PMID- 25779654
TI  - What can we learn from variation of red cell size distribution?

PMID- 25779655
TI  - P2Y2 receptor antagonists as anti-allodynic agents in acute and sub-chronic
      trigeminal sensitization: role of satellite glial cells.
AB  - Trigeminal (TG) pain often lacks a satisfactory pharmacological control. A better
      understanding of the molecular cross-talk between TG neurons and surrounding
      satellite glial cells (SGCs) could help identifying innovative targets for the
      development of more effective analgesics. We have previously demonstrated that
      neuronal pro-algogenic mediators upregulate G protein-coupled nucleotide P2Y
      receptors (P2YRs) expressed by TG SGCs in vitro. Here, we have identified the
      specific P2YR subtypes involved (i.e., the ADP-sensitive P2Y1 R and the UTP
      responsive P2Y2 R subtypes), and demonstrated the contribution of neuron-derived
      prostaglandins to their upregulation. Next, we have translated these data to an
      in vivo model of TG pain (namely, rats injected with Complete Freund's adjuvant
      in the temporomandibular joint), by demonstrating activation of SGCs and
      upregulation of P2Y1 R and P2Y2 R in the ipsi-lateral TG. To unequivocally link
      P2YRs to the development of facial allodynia, we treated animals with various
      purinergic antagonists. The selective P2Y2 R antagonist AR-C118925 completely
      inhibited SGCs activation, exerted a potent anti-allodynic effect that lasted
      over time, and was still effective when administration was started 6-days post
      induction of allodynia, i.e. under subchronic pain conditions. Conversely, the
      selective P2Y1 R antagonist MRS2179 was completely ineffective. Moreover,
      similarly to the anti-inflammatory drug acetylsalicylic acid and the known anti
      migraine agent sumatriptan, the P2X/P2Y nonselective antagonist PPADS was only
      partially effective, and completely lost its activity under sub-chronic
      conditions. Taken together, our results highlight glial P2Y2 Rs as potential
      "druggable" targets for the successful management of TG-related pain.

PMID- 25779656
TI  - Cartilage T1rho and T2 Relaxation Times in Patients With Mild-to-Moderate
      Radiographic Hip Osteoarthritis.
AB  - OBJECTIVE: To analyze region-specific T1rho and T2 relaxation times of the hip
      joint cartilage in relation to presence or absence of radiographic hip
      osteoarthritis (OA) and presence or absence of magnetic resonance imaging (MRI)
      detected cartilage defects. METHODS: Weight-bearing radiographs and 3T MRI
      studies of the hip were obtained from 84 volunteers. Based on Kellgren/Lawrence
      (K/L) scoring of the radiographs, 54 subjects were classified as healthy controls
      (K/L grade <=1) and 30 were classified as having mild or moderate radiographic
      hip OA (K/L grades 2 or 3, respectively). Two-dimensional fat-suppressed fast
      spin-echo MRI sequences were used for semiquantitative clinical scoring of
      cartilage defects, and a T1rho/T2 sequence was used to quantitatively assess the
      cartilage matrix. The femoral and acetabular cartilage was then segmented into 8
      regions and the mean T1rho/T2 values were calculated. Differences in T1rho and T2
      relaxation times were compared between subjects with and those without
      radiographic hip OA, and those with and those without femoral or acetabular
      cartilage defects. RESULTS: Higher T1rho and T2 relaxation times in the anterior
      superior and central regions of the acetabular cartilage were seen in individuals
      with radiographic hip OA and those with acetabular cartilage defects compared to
      their respective controls (P < 0.05). In the femoral cartilage, the differences
      in T1rho and T2 were not significant for any of the comparisons. Significant
      differences in the T1rho and T2 values (each P < 0.05) were found in more
      subregions of the cartilage and across the whole cartilage when subjects were
      stratified based on the presence of MRI-detected cartilage defects than when they
      were stratified based on the presence of radiographic hip OA. CONCLUSION: T1rho
      and T2 relaxation parameters are sensitive to the presence of cartilage
      degeneration. Both parameters may therefore support MRI evidence of cartilage
      defects of the hip.

PMID- 25779657
TI  - Elevated Src family kinase activity stabilizes E-cadherin-based junctions and
      collective movement of head and neck squamous cell carcinomas.
AB  - EGF receptor (EGFR) overexpression is thought to drive head and neck
      carcinogenesis however clinical responses to EGFR-targeting agents have been
      modest and alternate targets are actively sought to improve results. Src family
      kinases (SFKs), reported to act downstream of EGFR are among the alternative
      targets for which increased expression or activity in epithelial tumors is
      commonly associated to the dissolution of E-cadherin-based junctions and
      acquisition of a mesenchymal-like phenotype. Robust expression of total and
      activated Src was observed in advanced stage head and neck tumors (N=60) and in
      head and neck squamous cell carcinoma lines. In cultured cancer cells Src co
      localized with E-cadherin in cell-cell junctions and its phosphorylation on Y419
      was both constitutive and independent of EGFR activation. Selective inhibition of
      SFKs with SU6656 delocalized E-cadherin and disrupted cellular junctions without
      affecting E-cadherin expression and this effect was phenocopied by knockdown of
      Src or Yes. These findings reveal an EGFR-independent role for SFKs in the
      maintenance of intercellular junctions, which likely contributes to the cohesive
      invasion E-cadherin-positive cells in advanced tumors. Further, they highlight
      the need for a deeper comprehension of molecular pathways that drive collective
      cell invasion, in absence of mesenchymal transition, in order to combat tumor
      spread.

PMID- 25779658
TI  - Population analysis of microsatellite genotypes reveals a signature associated
      with ovarian cancer.
AB  - Ovarian cancer (OV) ranks fifth in cancer deaths among women, yet there remain
      few informative biomarkers for this disease. Microsatellites are repetitive
      genomic regions which we hypothesize could be a source of novel biomarkers for OV
      and have traditionally been under-appreciated relative to Single Nucleotide
      Polymorphisms (SNPs). In this study, we explore microsatellite variation as a
      potential novel source of genomic variation associated with OV. Exomes from 305
      OV patient germline samples and 54 tumors, sequenced as part of The Cancer Genome
      Atlas, were analyzed for microsatellite variation and compared to healthy females
      sequenced as part of the 1,000 Genomes Project. We identified a subset of 60
      microsatellite loci with genotypes that varied significantly between the OV and
      healthy female populations. Using these loci as a signature set, we classified
      germline genomes as 'at risk' for OV with a sensitivity of 90.1% and a
      specificity of 87.6%. Cross-analysis with a similar set of breast cancer
      associated loci identified individuals 'at risk' for both diseases. This study
      revealed a genotype-based microsatellite signature present in the germlines of
      individuals diagnosed with OV, and provides the basis for a potential novel risk
      assessment diagnostic for OV and new personal genomics targets in tumors. 

PMID- 25779659
TI  - Phospho-TCTP as a therapeutic target of Dihydroartemisinin for aggressive breast
      cancer cells.
AB  - Upregulation of Translationally Controlled Tumor Protein (TCTP) is associated
      with poorly differentiated aggressive tumors, including breast cancer, but the
      underlying mechanism(s) are still debated. Here, we show that in breast cancer
      cell lines TCTP is primarily localized in the nucleus, mostly in the
      phosphorylated form.The effects of Dihydroartemisinin (DHA), an anti-malaria
      agent that binds TCTP, were tested on breast cancer cells. DHA decreases cell
      proliferation and induces apoptotic cell death by targeting the phosphorylated
      form of TCTP. Remarkably, DHA enhances the anti-tumor effects of Doxorubicin in
      triple negative breast cancer cells resulting in an increased level of apoptosis.
      DHA also synergizes with Trastuzumab, used to treat HER2/neu positive breast
      cancers, to induce apoptosis of tumor cells.Finally, we present new clinical data
      that nuclear phospho-TCTP overexpression in primary breast cancer tissue is
      associated with high histological grade, increase expression of Ki-67 and with ER
      negative breast cancer subtypes. Notably, phospho-TCTP expression levels increase
      in trastuzumab-resistant breast tumors, suggesting a possible role of phospho
      TCTP as a new prognostic marker.In conclusion, the anti-tumor effect of DHA in
      vitro with conventional chemotherapeutics suggests a novel therapeutic strategy
      and identifies phospho-TCTP as a new promising target for advanced breast cancer.

PMID- 25779660
TI  - Traditional Chinese medicine herbal mixture LQ arrests FUCCI-expressing HeLa
      cells in G0/G1 phase in 2D plastic, 2.5D Matrigel, and 3D Gelfoam culture
      visualized with FUCCI imaging.
AB  - We used the fluorescence ubiquitination-based cell cycle indicator (FUCCI) to
      monitor cell cycle arrest after treatment of FUCCI-expressing HeLa cells (FUCCI
      HeLa) with a traditional Chinese medicine (TCM) herbal mixture LQ, previously
      shown to have anti-tumor and anti-metastatic activity in mouse models. Paclitaxel
      was used as the positive control. In 2D monolayer culture, the untreated control
      had approximately 45% of the cells in S/G2/M phase. In contrast, the LQ-treated
      cells (9 mg/ml) were mostly in the G0/G1 (>90%) after 72 hours. After treatment
      with paclitaxel (0.01 MUm), for 72 hours, 95% of the cells were in S/G2/M. In
      2.5D Matrigel culture, the colonies in the untreated control group had 40% of the
      cells in S/G2/M. LQ arrested the cells in G0/G1 after 72 hours. Paclitaxel
      arrested almost all the cells in S/G2/M after 72 hours. In 3D Gelfoam culture,
      the untreated control culture had approximately 45% of cells in G2/M. In
      contrast, the LQ-treated cells were mostly in G0/G1 phase (>80%) after 72 hours
      treatment. Paclitaxel resulted in 90% of the cells arrested in S/G2/M after 72
      hours. The present report suggests the non-toxic LQ has potential to maintain
      cancers in a quiescent state for long periods of time.

PMID- 25779661
TI  - Immunostimulatory effects of RACK1 pseudosubstrate in human leukocytes obtained
      from young and old donors.
AB  - Aims of this study were to investigate the ability of RACK1 pseudosubstrate alone
      or in combination with classical immune stimuli to activate human leukocytes, and
      to restore age-associated immune defects.A total of 25 donors (17 old donors, 77
      79 yrs; 8 young donors, 25-34 yrs) were enrolled. To evaluate the effect of RACK1
      pseudosubstrate on cytokine production and CD86 expression the whole blood assay
      was used. Cultures were treated with RACK1 pseudosubstrate in the presence or
      absence of lipopolysaccharide (LPS) or phytohaemagglutinin (PHA) and incubated
      for 24 h or 48 h for LPS-induced CD86 expression, TNF-alpha, IL-6, IL-8, IL-10
      production, and PHA-induced IL-4, IL-10, IFN-gamma, respectively. RACK1
      pseudosubstrate alone induced IL-6, IL-8, and CD86 expression in both young and
      old donors, and IFN-gamma in old donors. In combination with LPS an increase in
      IL-8, IL-10 and TNF-alpha was observed, also resulting in restoration of age
      associated defective production, while no changes in the other parameters
      investigated were found.Even if based on a small sample size, these results
      suggest the possibility to by-pass some of age-associated immune alterations,
      which may be beneficial in situations were natural immune stimulation is
      required, and highlight a different role of PKCbeta in immune cells activation. 

PMID- 25779662
TI  - High expression of inositol 1,4,5-trisphosphate receptor, type 2 (ITPR2) as a
      novel biomarker for worse prognosis in cytogenetically normal acute myeloid
      leukemia.
AB  - Inositol 1,4,5-trisphosphate receptor, type 2 (ITPR2) is a key regulator for the
      activity of calcium ion transmembrane transportation, which plays a critical role
      in cell cycle and proliferation. However, the clinical impact of ITPR2 in
      cytogenetically normal acute myeloid leukemia (CN-AML) remained unknown. Several
      microarray datasets were used to evaluate the association between ITPR2
      expression and clinical and molecular characteristics. ITPR2 showed a higher
      expression in CN-AML patients than normal persons. In a cohort of 157 CN-AML
      patients, high ITPR2 expression (ITPR2high) was associated with dramatically
      shorter overall survival (OS; P = 0.004) and event-free survival (EFS; P = 0.01),
      which were also shown in the European Leukemia Net (ELN) intermediate-I genetic
      category (OS: P = 0.0066; EFS: P = 0.009). Multivariable analyses adjusting for
      known prognostic factors confirmed ITPR2high to be associated with shorter OS (P
      = 0.0019) and EFS (P = 0.012). The prognostic value of ITPR2 was further
      validated in another cohort of 162 CN-AML patients (P = 0.007). In addition,
      first gene/microRNA expression signatures were derived that associated with
      ITPR2high on the genome-wide scale, which provided many indications to illustrate
      the possible mechanisms why ITPR2 could function. These results could aid to
      identify new targets and design novel therapeutic strategies for CN-AML patients.

PMID- 25779663
TI  - EGF-reduced Wnt5a transcription induces epithelial-mesenchymal transition via
      Arf6-ERK signaling in gastric cancer cells.
AB  - Wnt5a, a ligand for activating the non-canonical Wnt signaling pathway, is
      commonly associated with Epithelial-to-mesenchymal transition (EMT) in cancer
      cell metastasis. Here, we show that downregulation of Wnt5a mRNA and protein by
      EGF is necessary for EGF-induced EMT in gastric cancer SGC-7901 cells. To further
      explore the mechanisms, we investigated the effect of EGF signaling on Wnt5a
      expression. EGF increased Arf6 and ERK activity, while blockade of Arf6
      activation repressed ERK activity, up-regulated Wnt5a expression and repressed
      EMT in response to EGF. We also demonstrate that EGF inactivated Wnt5a
      transcription by direct recruitment of ERK to the Wnt5a promoter. On the other
      hand, inhibition of ERK phosphorylation resulted in decreased movement of ERK
      from the cytoplasm to the nucleus, following rescued Wnt5a mRNA and protein
      expression and favored an epithelial phenotype of SGC-7901 cells. In addition, we
      notice that kinase-dead, nuclear-localised ERK has inhibitory effect on Wnt5a
      transcription. Analysis of gastric cancer specimens revealed an inverse
      correlation between P-ERK and Wnt5a protein levels and an association between
      Wnt5a expression and better prognosis. These findings indicate that Wnt5a is a
      potential suppressor of EMT and identify a novel Arf6/ERK signaling pathway for
      EGF-regulated Wnt5a expression at transcriptional level of gastric cancer cells. 

PMID- 25779664
TI  - Prognostic factors of survival in patients treated with nab-paclitaxel plus
      gemcitabine regimen for advanced or metastatic pancreatic cancer: a single
      institutional experience.
AB  - PURPOSE: The objectives of this study were to evaluate the effectiveness of nab
      paclitaxel plus gemcitabine (NAB-P/GEM) regimen in an unselected population of
      patients with advanced inoperable or metastatic pancreatic cancer (PC), and to
      identify the prognostic factors influencing overall survival (OS). EXPERIMENTAL
      DESIGN: Patients with age < 85 years, ECOG-performance status (PS) < 3, and
      adequate renal, hepatic and hematologic function were eligible. NAB-P (125 mg/m2)
      and GEM (1000 mg/m2) day 1,8,15 every 4 weeks were employed for 3-6 cycles or
      until highest response. RESULTS: Overall, 147 cycles (median 4, range 1-11
      cycles) were administered on thirty-seven consecutive patients (median 66 years
      old, range 40-82) treated. The median overall progression-free survival and OS
      were 6.2 and 9.2 months, respectively. The G 3-4 dose-limiting toxicity were
      neutropenia (20.7%), severe anemia (17.2%), and cardiovascular toxicity (10.3%).
      PS, number of cycles, baseline CA 19-9 and LDH serum levels, were found to be
      significantly related to OS. The multivariate analysis showed that both number of
      cycles (HR = 9.14, 95% CI 1.84-45.50, p = 0.001) and PS (HR = 13.18, 95% CI 2.73
      63.71, p = 0.001) were independently associated with OS. CONCLUSION: NAB-P/GEM
      regimen should be used in all patients with advanced or metastatic PC, with the
      exception of those with serious contraindications to chemotherapy, such as severe
      renal or hepatic impairment or major cardiovascular diseases.

PMID- 25779665
TI  - UV irradiation/cold shock-mediated apoptosis is switched to bubbling cell death
      at low temperatures.
AB  - When COS7 fibroblasts and other cells were exposed to UVC irradiation and cold
      shock at 4 degrees C for 5 min, rapid upregulation and nuclear accumulation of
      NOS2, p53, WWOX, and TRAF2 occurred in 10-30 min. By time-lapse microscopy, an
      enlarging gas bubble containing nitric oxide (NO) was formed in the nucleus in
      each cell that finally popped out to cause "bubbling death". Bubbling occurred
      effectively at 4 and 22 degrees C, whereas DNA fragmentation was markedly blocked
      at 4 degrees C. When temperature was increased to 37 degrees C, bubbling was
      retarded and DNA fragmentation occurred in 1 hr, suggesting that bubbling death
      is switched to apoptosis with increasing temperatures. Bubbling occurred prior to
      nuclear uptake of propidium iodide and DAPI stains. Arginine analog Nomega-LAME
      inhibited NO synthase NOS2 and significantly suppressed the bubbling death.
      Unlike apoptosis, there were no caspase activation and flip-over of membrane
      phosphatidylserine (PS) during bubbling death. Bubbling death was significantly
      retarded in Wwox knockout MEF cells, as well as in cells overexpressing TRAF2 and
      dominant-negative p53. Together, UV/cold shock induces bubbling death at 4
      degrees C and the event is switched to apoptosis at 37 degrees C. Presumably,
      proapoptotic WWOX and p53 block the protective TRAF2 to execute the bubbling
      death.

PMID- 25779667
TI  - Improving the Dermatologic Care of Individuals with Autism: A Review of Relevant
      Issues and a Perspective.
AB  - Autism spectrum disorder (ASD) is a neurodevelopmental condition that effects
      verbal and nonverbal communication and social cognition and often presents with
      altered sensory processing, stereotyped behavior, and restricted interests. The
      prevalence of this diagnosis has increased markedly over the past two decades.
      Dermatologists undoubtedly will be evaluating and managing more patients with
      this diagnosis, but there has been little written regarding the dermatologic care
      of patients with ASD. Difficulties with communication and sensory processing
      create significant challenges in clinical evaluation and management. Individuals
      with ASD are also at higher risk for certain dermatologic conditions. This review
      is intended to build an awareness of the complexity of caring for individuals
      with ASD and discuss strategies that can help improve the dermatologic care of
      these patients. 

PMID- 25779666
TI  - Fatty acid binding protein 5 promotes metastatic potential of triple negative
      breast cancer cells through enhancing epidermal growth factor receptor stability.
AB  - Fatty acid binding protein 5 (FABP5), an intracellular lipid binding protein, has
      been shown to play a role in various cancers, including breast cancer. However,
      FABP5 and its role in triple negative breast cancer (TNBC) have not been studied.
      We show FABP5 protein expression correlates with TNBC, high grade tumors, and
      worse disease-free survival in a tissue microarray containing 423 breast cancer
      patient samples. High FABP5 expression significantly correlates with epidermal
      growth factor receptor (EGFR) expression in these samples. Decreased tumor growth
      and lung metastasis were observed in FABP5-/- mice othotopically injected with
      murine breast cancer cells. FABP5 loss in TNBC tumor cells inhibited motility and
      invasion. Mechanistic studies revealed that FABP5 knockdown in TNBC cells results
      in decreased EGFR expression and FABP5 is important for EGF-induced metastatic
      signaling. Loss of FABP5 leads to proteasomal targeting of EGFR. Our studies show
      that FABP5 has a role in both host and tumor cell during breast cancer
      progression. These findings suggest that FABP5 mediates its enhanced effect on
      TNBC metastasis, in part, through EGFR, by inhibiting EGFR proteasomal
      degradation. These studies show, for the first time, a correlation between FABP5
      and EGFR in enhancing TNBC metastasis through a novel mechanism. 

PMID- 25779668
TI  - Enzymatically active ultrathin pepsin membranes.
AB  - Enzymatically active proteins enable efficient and specific cleavage reactions of
      peptide bonds. Covalent coupling of the enzymes permits immobilization, which in
      turn reduces autolysis-induced deactivation. Ultrathin pepsin membranes were
      prepared by facile interfacial polycondensation of pepsin and trimesoyl chloride.
      The pepsin membrane allows for simultaneous enzymatic conversion and selective
      removal of digestion products. The large water fluxes through the membrane
      expedite the transport of large molecules through the pepsin layers. The
      presented method enables the large-scale production of ultrathin, cross-linked,
      enzymatically active membranes. 

PMID- 25779669
TI  - One hundred seventy-nine consecutive bariatric operations after introduction of
      protocol inspired by the principles of enhanced recovery after surgery (ERAS(r))
      in bariatric surgery.
AB  - BACKGROUND: Obese patients are a very large high-risk group for complications
      after surgical procedures. In this group, optimized perioperative care and a
      faster recovery to full activity can contribute to a decreased rate of
      postoperative complications. The introduction of ERAS(r)-based protocol is now
      even more important in bariatric surgery centers. The results of our study
      support the idea of implementation of ERAS(r)-based protocol in this special
      group of patients. MATERIAL AND METHODS: This analysis included 170 patients (62
      male/108 female, mean BMI 46.7 kg/m2) who had undergone laparoscopic bariatric
      surgery, and whose perioperative care was conducted according to a protocol
      inspired by ERAS(r) principles. Examined factors included oral nutrition
      tolerance, time until mobilization after surgery, requirements for opioids,
      duration of hospitalization, and readmission rate. RESULTS: During the first 24
      postoperative hours, oral administration of liquid nutrition was tolerated by 162
      (95.3%) patients and 163 (95.8%) were fully mobile. In 44 (25.8%) patients it was
      necessary to administer opioids to relieve pain. Intravenous liquid supply was
      discontinued within 24 hours in 145 (85.3%) patients. The complication rate was
      10.5% (mainly rhabdomyolysis and impaired passage of gastric contents). The
      average time of hospitalization was 2.9 days and the readmission rate was 1.7%.
      CONCLUSIONS: The introduction of an ERAS(r) principles-inspired protocol in our
      center proved technically possible and safe for our patients, and allowed for
      reduced hospitalization times without increased rate of complications or
      readmissions.

PMID- 25779670
TI  - Gradient gravitational search: An efficient metaheuristic algorithm for global
      optimization.
AB  - The adaptation of novel techniques developed in the field of computational
      chemistry to solve the concerned problems for large and flexible molecules is
      taking the center stage with regard to efficient algorithm, computational cost
      and accuracy. In this article, the gradient-based gravitational search (GGS)
      algorithm, using analytical gradients for a fast minimization to the next local
      minimum has been reported. Its efficiency as metaheuristic approach has also been
      compared with Gradient Tabu Search and others like: Gravitational Search, Cuckoo
      Search, and Back Tracking Search algorithms for global optimization. Moreover,
      the GGS approach has also been applied to computational chemistry problems for
      finding the minimal value potential energy of two-dimensional and three
      dimensional off-lattice protein models. The simulation results reveal the
      relative stability and physical accuracy of protein models with efficient
      computational cost.

PMID- 25779671
TI  - Human Wharton's jelly mesenchymal stem cell secretome display antiproliferative
      effect on leukemia cell line and produce additive cytotoxic effect in combination
      with doxorubicin.
AB  - Mesenchymal stem cell (MSC) therapy moves toward clinic progressively. Recent
      evidences establish anticancer effect of mesenchymal stem cells. However multiple
      factors including type of cancer, MSC source, study design, and animal model play
      role in final outcome. Wharton's jelly - a newly approved source of MSCs -
      possesses superiorities to bone marrow as the conventional source; therefore
      investigation of its medical effects can produce beneficial results. In this
      survey we examined cytotoxic and proapoptotic effect of human Wharton's jelly MSC
      secretome on K562 human leukemia cells. MSCs were isolated from human Wharton's
      jelly of umbilical cord by explant culture method, then characterized according
      to ISCT criteria (morphology and plastic adherence, surface antigenicity and
      differentiation potential). MSC secretome was collected and its cytotoxic and
      proapoptotic effects on K562 cells in combination with doxorubicin were evaluated
      using BrdU cell proliferation assay and Annexin V-PI staining. Our results showed
      antiproliferative effect of mesenchymal stem cell secretome on K562 cancer cells,
      the effect was also added to cytotoxic effect of doxorubicin without induction of
      drug resistance. Human Wharton's jelly derived mesenchymal stem cells exerted
      cytotoxic effect on leukemia cells. Addition of that effect to anticancer effect
      of chemotherapeutic agents can leads to cytotoxic drug dose reduction and
      diminished side effects. 

PMID- 25779672
TI  - The epidemiology of Scottish trauma: A comparison of pre-hospital and in-hospital
      deaths, 2000 to 2011.
AB  - AIMS: To characterise the temporal trends and urban-rural distribution of fatal
      injuries in Scotland through the analysis of mortality data collected by the
      National Records of Scotland. METHODS: The prospectively collected NRS database
      was queried using ICD-10 codes for all Scottish trauma deaths during the period
      2000 to 2011. Patients were divided into pre-hospital and in-hospital groups
      depending on the location of death. Incidence was plotted against time and linear
      regression was used to identify temporal trends. RESULTS: A total of 13,100
      deaths were analysed. There were 4755 (36.3%) patients in the pre-hospital group
      with a median age (IQR) of 42 (28-58) years. The predominant cause of pre
      hospital death related to vehicular injury (27.8%), which had a decreasing trend
      over the study period (p = 0.004). In-hospital, patients had a median age of 80
      (58-88) years and the majority (67.0%) of deaths occurred following a fall on the
      level. This trend was shown to increase over the decade of study (p = 0.020). In
      addition, the incidence of urban incidents remained static, but the rate of rural
      fatal trauma decreased (p < 0.001). CONCLUSIONS: Around a third of Scottish
      trauma patients die prior to hospital admission and the predominant mechanism of
      injury is due to road traffic accidents. This contrasts with in-hospital deaths,
      which are mainly observed in elderly patients following a fall from standing
      height. Further research is required to determine the preventability of fatal
      traumatic injury in Scotland.

PMID- 25779673
TI  - FOXA2 attenuates the epithelial to mesenchymal transition by regulating the
      transcription of E-cadherin and ZEB2 in human breast cancer.
AB  - The Forkhead Box A2 (FOXA2) transcription factor is required for embryonic
      development and for normal functions of multiple adult tissues, in which the
      maintained expression of FOXA2 is usually related to preventing the progression
      of malignant transformation. In this study, we found that FOXA2 prevented the
      epithelial to mesenchymal transition (EMT) in human breast cancer. We observed a
      strong correlation between the expression levels of FOXA2 and the epithelial
      phenotype. Knockdown of FOXA2 promoted the mesenchymal phenotype, whereas stable
      overexpression of FOXA2 attenuated EMT in breast cancer cells. FOXA2 was found to
      endogenously bind to and stimulate the promoter of E-cadherin that is crucial for
      epithelial phenotype of the tumor cells. Meanwhile, FOXA2 prevented EMT of breast
      cancer cells by repressing the expression of EMT-related transcription factor
      ZEB2 through recruiting a transcriptional corepressor TLE3 to the ZEB2 promoter.
      The stable overexpression of FOXA2 abolished metastasis of breast cancer cells in
      vivo. This study confirmed that FOXA2 inhibited EMT in breast cancer cells by
      regulating the transcription of EMT-related genes such as E-cadherin and ZEB2. 

PMID- 25779674
TI  - Peroxiredoxin 4: a novel secreted mediator of cancer induced osteoclastogenesis.
AB  - Bone is a common site of metastasis from breast and prostate carcinoma, where
      activation of bone resorbing osteoclasts is important for cancer progression. A
      large body of evidence indicates that soluble factors produced by the cancer
      cells act to promote osteoclast formation. Using mass spectrometry, we identified
      peroxiredoxin (PRDX) as a secreted mediator of cancer-induced osteoclastogenesis.
      Both breast (MCF7 and MDA-MB-231) and prostate (PC3 and LNCaP) carcinoma cells
      secreted PRDX4. PRDX4 knockdown using shRNA (shPRDX4) diminished PRDX4 secretion
      from MDA-MB-231 and PC3 cells and significantly decreased the ability of cancer
      derived factors to induce osteoclast formation from late precursors in vitro.
      Tibial injection of shPRDX4 PC3 cells led to the development of significantly
      smaller osteolytic lesions characterized by significantly reduced osteoclast
      numbers compared to control PC3 cells. A meta-analysis demonstrated an increase
      in PRDX4 mRNA expression in carcinoma and metastatic breast and prostate tissues.
      Moreover, high expression of PRDX4 in the primary breast tumor was consistently
      associated with metastasis at 5 years. These data identify a novel function of
      secreted PRDX4 in mediating osteoclast activation by cancer cells. 

PMID- 25779675
TI  - Adipose tissue macrophage polarization by intermittent hypoxia in a mouse model
      of OSA: effect of tumor microenvironment.
AB  - Intermittent hypoxia (IH)-induces alterations in tumor-associated macrophages
      (TAMs) that are associated with adverse cancer outcomes, as reported in patients
      suffering from sleep apnea. Adipose tissues (AT) and bone-marrow (BM)-derived
      cells are the inferred sources of macrophages infiltrating malignant tumors.
      Here, the sources of TAMs and the phenotypic changes induced by IH in the
      ipsilateral and contralateral AT were investigated by using a syngeneic murine
      solid tumor model (TC1). C57/B6 male mice were exposed to either IH or room air
      (RA) for 6 weeks, with TC1 cells being inoculated in the 2nd week. Macrophage
      content, phenotype and tissue origin were assessed in tumors, and ipsilateral and
      contralateral AT. IH induced a ~2.2-fold increase in TAM tumor infiltration.
      However, differential responses in the tumor ipsilateral and contralateral AT
      emerged: IH increased infiltration of preferentially M1 macrophages in
      contralateral AT, while reductions in macrophages emerged in ipsilateral AT and
      primarily consisted of the M2 phenotype. These changes were accompanied by
      reciprocal increases in resident and BM-derived TAMs in the tumor. IH-induced
      phenotypic alterations in AT macrophages surrounding the tumor and their
      increased infiltration within the tumor may contribute to the accelerated tumor
      progression associated with IH. 

PMID- 25779677
TI  - We need a drug formulary for obese people.

PMID- 25779676
TI  - REG3A accelerates pancreatic cancer cell growth under IL-6-associated
      inflammatory condition: Involvement of a REG3A-JAK2/STAT3 positive feedback loop.
AB  - Regenerating gene protein (REG) 3A is a 19 kD secretory pancreas protein with pro
      growth function. Previously we demonstrated that overexpression of REG3A, acting
      as a key molecule for up-regulation of the JAK2/STAT3 pathway, contributed to
      inflammation-related pancreatic cancer (PaC) development. However the exact
      network associated with REG3A signaling still remains unclear. Here we determined
      that exposure of human PaC cells to cytokine IL-6 activated the oncogenic
      JAK2/STAT3 pathway, which directly upregulated REG3A expression, accelerated cell
      cycle progression by promoting CyclinD1 expression, and enhancing the expression
      of the anti-apoptosis Bcl family. Importantly, the activation of REG3A would
      instead enhance the JAK2/STAT3 pathway to constitute a REG3A-JAK2/STAT3 positive
      feedback loop, which leads to the amplification of the oncogenic effects of IL
      6/JAK2/STAT3, a classic pathway linking to inflammation-related tumorigenesis,
      ultimately resulting in PaC cell over-proliferation and tumor formation both in
      vitro and in vivo. Moreover, EGFR was found to mediate the REG3A signal for PaC
      cell growth and JAK2/STAT3 activation, thus functioning as a REG3A receptor.
      Collectively, our results provide the first evidence for the presence of the
      synergistic effect of REG3A and IL-6 on PaC development via a REG3A-JAK2/STAT3
      positive feedback loop.

PMID- 25779678
TI  - A retrospective analysis to determine factors contributing to the survival of
      patients with oral squamous cell carcinoma.
AB  - The clinical outcome of patients with OSCC is assessed based on TNM system and
      currently it is the most reliable indicator on which therapeutic decisions are
      made. The patients with advanced disease are managed with combined treatment
      modalities. The aim of this retrospective study was to identify the factors which
      influence survival of patients with OSCC in Sri Lanka. Four hundred and thirty
      patients who have been managed surgically using either (1) local excision, (2)
      local excision+supraomohyoid neck dissection, (3) local excision+modified radical
      neck dissection, (4) local excision+radical neck dissection, (5) local
      excision+contra-lateral neck dissection depending on TNM stage, with or without
      post-operative radiotherapy. Patients with incompletely excised tumours showed
      statistically significant poor survival which improved with radiotherapy (stage
      II P=0.002, stage III P=0.017). With reference to TNM stage IV tumours, the
      patients who had received surgical option 4, showed poor survival compared to
      surgical options 2, 3, and 5 (P=0.001). However, within the group of patients who
      had received surgical option 4, those who had nodal metastasis showed poorer
      survival compared to patients without nodal metastasis. In addition, survival
      improved in patients who had been treated with surgical option 4, with
      radiotherapy. Furthermore, margin status was also found to significantly
      influence the survival of patients with TNM stage IV tumours (P=0.003). The main
      factors that had significant impact on the survival were TNM stage, nodal
      metastasis and the state of excision margins. 

PMID- 25779679
TI  - Social relationships and risk of dementia: a population-based study.
AB  - BACKGROUND: The objective was to examine whether aspects of social relationships
      in old age are associated with all-cause dementia and Alzheimer's disease (AD).
      METHODS: We studied 1,715 older adults (>= 65 years) who were dementia-free at
      baseline over a period of up to 16 years. Data on living status, contact/visit
      frequency, satisfaction with contact frequency, and having/not having a close
      friend were analyzed using Cox proportional hazards regressions with all-cause
      dementia or AD as the dependent variable. To control for reverse causality and to
      identify potential long-term effects, we additionally performed analyses with
      delayed entry. RESULTS: We identified 373 incident cases of dementia (207 with
      AD) during follow-up. The variable visiting/visits from friends was associated
      with reduced risk of all-cause dementia. Further, a higher value on the
      relationships index (sum of all variables) was associated with reduced risk of
      all-cause dementia and AD. However, in analyses with delayed entry, restricted to
      participants with a survival time of three years or more, none of the social
      relationship variables was associated with all-cause dementia or AD. CONCLUSIONS:
      The results indicate that certain aspects of social relationships are associated
      with incident dementia or AD, but also that these associations may reflect
      reverse causality. Future studies aimed at identifying other factors of a
      person's social life that may have the potential to postpone dementia should
      consider the effects of reverse causality.

PMID- 25779680
TI  - Honey and green/black tea consumption may reduce the risk of Helicobacter pylori
      infection.
AB  - The aim of the study was to evaluate the influence of dietary and demographic
      factors and some habits on the prevalence of Helicobacter pylori infection in 150
      dyspeptic patients examined endoscopically and by the urea breath test.
      Positivity rate was lower (50.6%) in patients consuming honey >=1 day weekly
      compared with the remainder (70.8%) and in those consuming green/black tea >=1
      day weekly (45.2%) compared with the other patients (64.8%). Logistic regression
      confirmed that the factors associated with significantly lower H. pylori
      positivity rate were the consumption of honey (odds ratio [OR], 0.38; 95%
      confidence interval [CI], 0.19-0.78) and green/black tea (OR, 0.45; 95% CI, 0.21
      0.95). In conclusion, honey and green/black tea intake is associated with reduced
      prevalence of H. pylori infection.

PMID- 25779681
TI  - Nanocomplexation between curcumin and soy protein isolate: influence on curcumin
      stability/bioaccessibility and in vitro protein digestibility.
AB  - The complexation of nanoparticles in unheated and heated (at 75-95 degrees ) soy
      protein isolate (SPI) with curcumin and the effects on curcumin
      stability/bioaccessibility and in vitro protein digestibility were investigated.
      The nanoparticles did not display noticeable changes in size and morphology upon
      nanocomplexation with curcumin, except their surface hydrophobicity. The
      encapsulation efficiency of curcumin progressively decreased with increasing
      initial curcumin concentration in the dispersion, while the load amount linearly
      increased. The solubility of curcumin in water was enhanced by the complexation
      above 98000-fold (vs free curcumin in water). The formation of the nanocomplexes
      considerably improved the storage stability of curcumin. In vitro simulated
      digestion experiments indicated that the complexation also improved the
      bioaccessibility of curcumin; the bioaccessibility was greatly impaired by
      hydrolysis-induced protein aggregation. Addtionally, the nanocomplexation
      significantly improved the in vitro protein digestibility of both unheated and
      heated SPI. 

PMID- 25779682
TI  - Correction to: Once-daily LCP-Tacro MeltDose tacrolimus for the prophylaxis of
      organ rejection in kidney and liver transplantations.

PMID- 25779683
TI  - Dual Functioning Thieno-Pyrrole Fused BODIPY Dyes for NIR Optical Imaging and
      Photodynamic Therapy: Singlet Oxygen Generation without Heavy Halogen Atom
      Assistance.
AB  - We discovered a rare phenomenon wherein a thieno-pyrrole fused BODIPY dye
      (SBDPiR690) generates singlet oxygen without heavy halogen atom substituents.
      SBDPiR690 generates both singlet oxygen and fluorescence. To our knowledge, this
      is the first example of such a finding. To establish a structure-photophysical
      property relationship, we prepared SBDPiR analogs with electron-withdrawing
      groups at the para-position of the phenyl groups. The electron-withdrawing groups
      increased the HOMO-LUMO energy gap and singlet oxygen generation. Among the
      analogs, SBDPiR688, a CF3 analog, had an excellent dual functionality of
      brightness (82290 m(-1)  cm(-1) ) and phototoxic power (99170 m(-1)  cm(-1) )
      comparable to those of Pc 4, due to a high extinction coefficient (211 000 m(-1) 
      cm(-1) ) and balanced decay (Phiflu =0.39 and PhiDelta =0.47). The dual
      functionality of the lead compound SBDPiR690 was successfully applied to
      preclinical optical imaging and for PDT to effectively control a subcutaneous
      tumor. 

PMID- 25779684
TI  - A novel 1,8-naphthalimide derivative with an open space for an anion: unique
      fluorescence behaviour depending on the binding anion's electrophilic properties.
AB  - We have designed a novel 1,8-naphthalimide derivative with an open space for an
      anion. Computational calculation has predicted that the space could trap various
      anion species and photo-induced charge transfer depending on the anion's
      electrophilic properties. Indeed, the fluorescence behaviour of the 1,8
      naphthalimide derivative complexes with each anion is consistent with the
      computational prediction. 

PMID- 25779685
TI  - A unique pattern of delayed enhancement of a large cardiac fibroma on magnetic
      resonance imaging.
AB  - MRI is a valuable noninvasive tool that helps in predicting the type of cardiac
      tumors and guiding management decisions. Several reports have described the
      appearance of cardiac fibromas on MRI, which typically show hyperenhancement on
      myocardial delayed enhancement (MDE) imaging, with or without a dark core. This
      report demonstrates the unique appearance of a large solitary ventricular septal
      cardiac fibroma in a 5-month-old patient on MDE imaging, with two discrete dark
      cores, each surrounded by a hyperenhancing pseudocapsule. 

PMID- 25779686
TI  - Generation of hyper-entanglement in polarization/energy-time and discrete
      frequency/energy-time in optical fibers.
AB  - In this paper, a generation scheme for telecom band hyper-entanglement is
      proposed and demonstrated based on the vector spontaneous four wave mixing (SFWM)
      processes in optical fibers. Two kinds of two-photon states are generated, one is
      hyper-entangled in the degree of freedoms (DOFs) of energy-time and polarization,
      the other is hyper-entangled in DOFs of energy-time and discrete-frequency.
      Experiments of Franson-type interference, two-photon interference under non
      orthogonal polarization bases and spatial quantum beating are realized to
      demonstrate the entanglement in energy-time, polarization and frequency,
      respectively. This scheme provides a simple way to realize telecom band hyper
      entanglement, which has potential for large geographic-scale applications of
      quantum communication and quantum information over optical fibers. 

PMID- 25779687
TI  - Continuity of care trajectories and emergency room use among patients with
      diabetes.
AB  - OBJECTIVES: To analyze the pattern of continuity of care (COC) using trajectory
      analysis for a group of patients newly diagnosed with diabetes, and determine
      whether various trajectories lead to distinct patient outcomes. METHODS: We used
      the Taiwan National Health Insurance claims database. Newly diagnosed patients
      with diabetes in 2005 totaling 4367 were included in this study. All patients
      were followed up to 2011. We identified groups of COC trajectories using
      trajectory analysis. We subsequently determined whether various COC trajectories
      were associated with the frequency of total and diabetes-related emergency room
      (ER) use using negative binomial models. RESULTS: We discovered five distinct COC
      trajectories for our newly diagnosed diabetes sample based on trajectory
      analysis. The early-seeker group had the lowest IRR for total ER visits (IRR =
      0.56, P < 0.001), followed by the high-maintainer group (IRR = 0.67, P < 0.001).
      Similar results were obtained for diabetes-specific ER use. CONCLUSIONS: We
      identified various COC trajectories for diabetes patients. Chronic disease
      patients may seek a suitable physician by compromising care continuity at the
      onset of disease progression and exhibit favorable outcome.

PMID- 25779688
TI  - Impedance sensing device enables early detection of pressure ulcers in vivo.
AB  - When pressure is applied to a localized area of the body for an extended time,
      the resulting loss of blood flow and subsequent reperfusion to the tissue causes
      cell death and a pressure ulcer develops. Preventing pressure ulcers is
      challenging because the combination of pressure and time that results in tissue
      damage varies widely between patients, and the underlying damage is often severe
      by the time a surface wound becomes visible. Currently, no method exists to
      detect early tissue damage and enable intervention. Here we demonstrate a
      flexible, electronic device that non-invasively maps pressure-induced tissue
      damage, even when such damage cannot be visually observed. Using impedance
      spectroscopy across flexible electrode arrays in vivo on a rat model, we find
      that impedance is robustly correlated with tissue health across multiple animals
      and wound types. Our results demonstrate the feasibility of an automated, non
      invasive 'smart bandage' for early detection of pressure ulcers. 

PMID- 25779689
TI  - Biomechanical effect of interspinous dynamic stabilization adjacent to single
      level fusion on range of motion of the transition segment and the adjacent
      segment.
AB  - BACKGROUND: Despite numerous biomechanical studies have been carried out on
      dynamic stabilizers, there is very little information on their hybrid
      application, especially when combined interspinous dynamic stabilization with
      single-level fusion. The aim of this study is to assess the biomechanical effect
      of interspinous dynamic stabilization adjacent to single-level fusion on range of
      motion of the transition segment and the adjacent segment. METHODS: Six fresh
      lumbosacral spines (L2-S1) were tested in the following sequence: 1) intact
      (Construct A); 2) fusion in L5/S1 and intact in L4/5 (Construct B); 3) fusion in
      L5/S1 and unstable state in L4/5 (Construct C); 4) fusion in L5/S1 and Coflex in
      L4/5 (Construct D). Range of motion (at L3/4 and L4/5) was recorded and
      calculated. FINDINGS: Range of motion in L3/4 in the four constructs showed no
      difference under all motion states. Under flexion/extension, the range of motion
      of L4/5 in Construct B and Construct C increased, while the range of motion of
      L4/5 in Construct D decreased compared with Construct A. Compared with Construct
      D, the range of motion of L4/5 in Constructs B and C showed a significant
      increase. Under lateral bending and axial rotation, Construct A showed similar
      range of motion of L3/4 compared with other constructs. INTERPRETATION: Fusion
      combined with Coflex is able to stabilize the transition segment and restrict
      flexion and extension in that segment, while having no significant effect on the
      range of motion of the adjacent segment or the range of motion of the transition
      segment under lateral bending and axial rotation.

PMID- 25779690
TI  - The effects of laterality on obstacle crossing performance in unilateral trans
      tibial amputees.
AB  - BACKGROUND: Unilateral trans-tibial amputees have bilaterally reduced toe
      clearance, and an increased risk of foot contact, while crossing obstacles
      compared to the able-bodied. While the able-bodied tend to lead with a
      'preferred' limb it is equivocal whether amputees prefer to lead with the intact
      or prosthetic limb. This study determined the effects of laterality, compared to
      side of amputation, on amputees' obstacle crossing performance. To help
      understand why laterality could affect performance we also assessed knee
      proprioception for both limbs. METHODS: Foot placement and toe clearance
      parameters were recorded while nine amputees crossed obstacles of varying heights
      leading with both their intact and prosthetic limbs. Joint-position sense was
      also assessed. Participants self-reported which limb was their preferred
      (dominant) limb. FINDINGS: There were no significant differences in foot
      placements or toe clearance variability across lead-limb conditions. There were
      no significant differences in toe clearance between intact and prosthetic lead
      limbs (p=0.28) but toe clearance was significantly higher when amputees led with
      their preferred compared to non-preferred limb (p=0.025). There was no difference
      in joint-position sense between the intact and residual knees (p=0.34) but joint
      position sense tended to be more accurate for the preferred, compared to non
      preferred limb (p=0.08). INTERPRETATION: Findings suggest that, despite the
      mechanical constraints imposed by use of a prosthesis, laterality may be as
      important in lower-limb amputees as it is in the able bodied. This suggests that
      amputees should be encouraged to cross obstacles leading with their preferred
      limb.

PMID- 25779691
TI  - Public open space, physical activity, urban design and public health: Concepts,
      methods and research agenda.
AB  - Public open spaces such as parks and green spaces are key built environment
      elements within neighbourhoods for encouraging a variety of physical activity
      behaviours. Over the past decade, there has been a burgeoning number of active
      living research studies examining the influence of public open space on physical
      activity. However, the evidence shows mixed associations between different
      aspects of public open space (e.g., proximity, size, quality) and physical
      activity. These inconsistencies hinder the development of specific evidence-based
      guidelines for urban designers and policy-makers for (re)designing public open
      space to encourage physical activity. This paper aims to move this research
      agenda forward, by identifying key conceptual and methodological issues that may
      contribute to inconsistencies in research examining relations between public open
      space and physical activity. 

PMID- 25779692
TI  - The effect of emotional stress and depression on the prevalence of digestive
      diseases.
AB  - BACKGROUND/AIMS: Epidemiological data indicate that emotional stress and
      depression might influence the development of gastrointestianl disorders and
      cancers, but the relationship between the two is still unclear. The aim was to
      investigate the effect of stress/depression on the prevalence of digestive
      diseases. In addition, we tried to identify whether stress and depression are
      risk factors for these diseases. METHODS: A total of 23 698 subjects who
      underwent a medical check-up including upper and lower endoscopy were enrolled.
      By reviewing the subject's self-reporting questionnaire and endoscopic findings,
      we investigated the digestive diseases, including functional dyspepsia (FD),
      irritable bowel syndrome (IBS), reflux esophagitis, peptic ulcer disease, and
      adenoma and carcinoma of the stomach and colon. Stress and depression scores were
      measured by the Brief Encounter Psychosocial Instrument and Beck's Depression
      Inventory, respectively (Korean version). RESULTS: Stress and depression were
      related to FD, IBS, and reflux esophagitis. Depression was also linked to peptic
      ulcer disease and adenoma/carcinoma of the colon and stomach. Multivariate
      analysis revealed that stress and depression were independent risk factors for FD
      (OR, 1.713 and 1.984; P < 0.001) and IBS (OR, 1.730 and 3.508; P < 0.001). In
      addition, depression was an independent risk factor for gastric adenoma/carcinoma
      (OR, 4.543; P < 0.001). CONCLUSIONS: Stress and depression are related to various
      digestive diseases, and they may be predisposing factors for FD and IBS.
      Depression may also be a cause of gastric cancer. Psychological evaluation of
      gastroenterology patients may be necessary, but more study is needed.

PMID- 25779693
TI  - IFN-alpha production by plasmacytoid dendritic cell associations with
      polymorphisms in gene loci related to autoimmune and inflammatory diseases.
AB  - The type I interferon (IFN) system is persistently activated in systemic lupus
      erythematosus (SLE) and many other systemic autoimmune diseases. Studies have
      shown an association between SLE and several gene variants within the type I IFN
      system. We investigated whether single-nucleotide polymorphisms (SNPs) associated
      with SLE and other autoimmune diseases affect the IFN-alpha production in healthy
      individuals. Plasmacytoid dendritic cells (pDCs), B cells and NK cells were
      isolated from peripheral blood of healthy individuals and stimulated with RNA
      containing immune complexes (ICs), herpes simplex virus (HSV) or the
      oligonucleotide ODN2216. IFN-alpha production by pDCs alone or in cocultures with
      B or NK cells was measured by an immunoassay. All donors were genotyped with the
      200K ImmunoChip, and a 5 bp CGGGG length polymorphism in the IFN regulatory
      factor 5 gene (IRF5) was genotyped by PCR. We found associations between IFN
      alpha production and 18-86 SNPs (P <= 0.001), depending on the combination of the
      stimulated cell types. However, only three of these associated SNPs were shared
      between the cell-type combinations. Several SNPs showed novel associations to the
      type I IFN system among all the associated SNPs, whereas some loci have been
      described earlier for their association with SLE. Furthermore, we found that the
      SLE-risk variant of the IRF5 CGGGG-indel was associated with lower IFN-alpha
      production. We conclude that the genetic variants affecting the IFN-alpha
      production highlight the intricate regulation of the type I IFN system and the
      importance of understanding the mechanisms behind the dysregulated type I IFN
      system in SLE. 

PMID- 25779694
TI  - Applying Health Locus of Control and Latent Class Modelling to food and physical
      activity choices affecting CVD risk.
AB  - Health Locus of Control (HLC) classifies our beliefs about the connection between
      our actions and health outcomes (Skinner, 1996) into three categories: "internal
      control", corresponding to health being the result of an individual's effort and
      habits; "control by powerful others", whereby health depends on others, such as
      doctors; and "chance control", according to which health depends on fate and
      chance. Using Choice Experiments we investigate the relationship between HLC and
      willingness to change lifestyle, in terms of eating habits, physical activity and
      associated cardiovascular disease risk, in a 384 person sample representative of
      the 40-65 aged population of Northern Ireland administered between February and
      July 2011. Using latent class analysis we identify three discrete classes of
      people based on their HLC: the first class is sceptical about their capacity to
      control their health and certain unhealthy habits. Despite being unsatisfied with
      their situation, they are reluctant to accept behaviour changes. The second is a
      group of individuals unhappy with their current situation but willing to change
      through exercise and diet. Finally, a group of healthy optimists is identified,
      who are satisfied with their current situation but happy to take more physical
      activity and improve their diet. Our findings show that any policy designed to
      modify people's health related behaviour should consider the needs of this
      sceptical class which represents a considerable proportion of the population in
      the region. 

PMID- 25779696
TI  - Umbilical and fetal middle cerebral artery Doppler at 35-37 weeks' gestation in
      the prediction of adverse perinatal outcome.
AB  - OBJECTIVE: To investigate the potential value of cerebroplacental ratio (CPR) at
      36 weeks' gestation in the prediction of adverse perinatal outcome. METHODS: This
      was a screening study in 6178 singleton pregnancies at 35-37 weeks' gestation.
      Umbilical artery (UA) and fetal middle cerebral artery (MCA) pulsatility index
      (PI) were measured and the values were converted to multiples of the median (MoM)
      after adjustment from variables in maternal characteristics and medical history
      that affect the measurements. CPR was calculated by dividing MCA-PI MoM by UA-PI
      MoM. Multivariable logistic regression analysis was used to determine if
      measuring CPR improved the prediction of adverse perinatal outcome provided by
      maternal characteristics, medical history and obstetric factors. The detection
      rate (DR) and false-positive rate (FPR) of screening by CPR were estimated for
      stillbirth, Cesarean section for fetal distress, umbilical arterial cord blood pH
      <= 7.0, umbilical venous cord blood pH <= 7.1, 5-min Apgar score < 7 and
      admission to the neonatal unit (NNU) and neonatal intensive care unit (NICU).
      RESULTS: There was a linear association between CPR and both birth-weight Z-score
      and arterial or venous umbilical cord blood pH, but the steepness of the
      regression lines was inversely related to the interval from assessment to
      delivery. The performance of low CPR < 5(th) percentile in screening for each
      adverse outcome was poor, with DRs of 6-15% and a FPR of about 6%. In the small
      subgroup of the population delivering within 2 weeks of assessment, the DRs
      improved to 14-50%, but with a simultaneous increase in FPR, to about 10%.
      CONCLUSION: The performance of CPR in routine screening for adverse perinatal
      outcome at 36 weeks' gestation is poor.

PMID- 25779695
TI  - Emergency department revisits for patients with kidney stones in California.
AB  - OBJECTIVES: Kidney stones affect nearly one in 11 persons in the United States,
      and among those experiencing symptoms, emergency care is common. In this
      population, little is known about the incidence of and factors associated with
      repeat emergency department (ED) visits. The objective was to identify
      associations between potentially mutable factors and the risk of an ED revisit
      for patients with kidney stones in a large, all-payer cohort. METHODS: This was a
      retrospective cohort study of all patients in California initially treated and
      released from EDs for kidney stones between February 2008 and November 2009. A
      multivariable regression model was created to identify associations between
      patient-level characteristics, area health care resources, processes of care, and
      the risk of repeat ED visits. The primary outcome was a second ED visit within 30
      days of the initial discharge from emergent care. RESULTS: Among 128,564 patients
      discharged from emergent care, 13,684 (11%) had at least one additional emergent
      visit for treatment of their kidney stone. In these patients, nearly one in three
      required hospitalization or an urgent temporizing procedure at the second visit.
      On multivariable analysis, the risk of an ED revisit was associated with
      insurance status (e.g., Medicaid vs. private insurance; odds ratio [OR] = 1.52,
      95% confidence interval [CI] = 1.43 to 1.61; p < 0.001). Greater access to
      urologic care was associated with lower odds of an ED revisit (highest quartile
      OR = 0.88, 95% CI = 0.80 to 0.97; p < 0.01 vs. lowest quartile). In exploratory
      models, performance of a complete blood count was associated with a decreased
      odds of revisit (OR = 0.86, 95% CI = 0.75 to 0.97; p = 0.02). CONCLUSIONS: Repeat
      high-acuity care affects one in nine patients discharged from initial emergent
      evaluations for kidney stones. Access to urologic care and processes of care are
      associated with lower risk of repeat emergent encounters. Efforts are indicated
      to identify preventable causes of ED revisits for kidney stone patients and
      design interventions to reduce the risk of high-cost, high-acuity, repeat care.

PMID- 25779697
TI  - One-year neurodevelopmental outcome of very and late preterm infants: Risk
      factors and correlation with maternal stress.
AB  - Although "late preterm" (LP) newborns (33-36 weeks of gestational age) represent
      more than 70% of all preterm labors, little is known about the relation between
      certain risk factors and developmental outcomes in LP compared to "very preterm"
      (<=32 weeks) children (VP). This study investigates: (1) LP and VP infants'
      development at 12 months of corrected age (CA) using the Bayley Scales of Infant
      Development - 3rd Edition (BSID-III); (2) correlation between BSID-III
      performances and maternal stress (using Parenting Stress Index-Short Form, PSI
      SF) among LP and VP at 12 months CA; and (3) the link between known neonatal and
      demographic risk factors and developmental outcomes of LP and VP infants. For
      both LP and VP infants the Mean Cognitive (LP: 102.69+/-7.68; VP: 103.63+/
      10.68), Language (LP: 96.23+/-10.08; VP: 99.10+/-10.37) and Motor (LP: 91.11+/
      10.33; VP: 93.85+/-10.17) composite scores were in the normal range, without
      significant differences between the groups. Correlations between PSI-SF and BSID
      III showed that in the VP group (but not LP), Language score was negatively
      related to the PSI-SF 'Difficult Child' scale (r=-.34, p<.05). Regression models
      revealed that cognitive performance was significantly predicted by physical
      therapy in LP and by cesarean section in VP infants. For VP only maternal
      education and length of stay predicted Language score, whereas physical therapy
      predicted Motor score. Results of the study underline the importance of
      considering cognitive, language and motor developments separately when assessing
      a preterm child's development. Prediction models of developmental performance
      confirm the influence of some known neonatal risk factors and indicate the need
      for further research on the role of sociodemographic risk factors. 

PMID- 25779698
TI  - Diabetes and onset of natural menopause: results from the European Prospective
      Investigation into Cancer and Nutrition.
AB  - STUDY QUESTION: Do women who have diabetes before menopause have their menopause
      at an earlier age compared with women without diabetes? SUMMARY ANSWER: Although
      there was no overall association between diabetes and age at menopause, our study
      suggests that early-onset diabetes may accelerate menopause. WHAT IS KNOWN
      ALREADY: Today, more women of childbearing age are being diagnosed with diabetes,
      but little is known about the impact of diabetes on reproductive health. STUDY
      DESIGN, SIZE, DURATION: We investigated the impact of diabetes on age at natural
      menopause (ANM) in 258 898 women from the European Prospective Investigation into
      Cancer and Nutrition (EPIC), enrolled between 1992 and 2000.
      PARTICIPANTS/MATERIALS, SETTING, METHODS: Determinant and outcome information was
      obtained through questionnaires. Time-dependent Cox regression analyses were used
      to estimate the associations of diabetes and age at diabetes diagnosis with ANM,
      stratified by center and adjusted for age, smoking, reproductive and diabetes
      risk factors and with age from birth to menopause or censoring as the underlying
      time scale. MAIN RESULTS AND THE ROLE OF CHANCE: Overall, no association between
      diabetes and ANM was found (hazard ratio (HR) = 0.94; 95% confidence interval
      (CI) 0.89-1.01). However, women with diabetes before the age of 20 years had an
      earlier menopause (10-20 years: HR = 1.43; 95% CI 1.02-2.01, <10 years: HR =
      1.59; 95% CI 1.03-2.43) compared with non-diabetic women, whereas women with
      diabetes at age 50 years and older had a later menopause (HR = 0.81; 95% CI 0.70
      0.95). None of the other age groups were associated with ANM. LIMITATIONS,
      REASONS FOR CAUTION: Strengths of the study include the large sample size and the
      broad set of potential confounders measured. However, results may have been
      underestimated due to survival bias. We cannot be sure about the sequence of the
      events in women with a late age at diabetes, as both events then occur in a short
      period. We could not distinguish between type 1 and type 2 diabetes. WIDER
      IMPLICATIONS OF THE FINDINGS: Based on the literature, an accelerating effect of
      early-onset diabetes on ANM might be plausible. A delaying effect of late-onset
      diabetes on ANM has not been reported before, and is not in agreement with recent
      studies suggesting the opposite association. STUDY FUNDING/COMPETING INTERESTS:
      The coordination of EPIC is financially supported by the European Commission (DG
      SANCO) and the International Agency for Research on Cancer. The national cohorts
      are supported by Danish Cancer Society (Denmark); Ligue Contre le Cancer,
      Institut Gustave Roussy, Mutuelle Generale de l'Education Nationale, Institut
      National de la Sante et de la Recherche Medicale (INSERM) (France); German Cancer
      Aid, German Cancer Research Center (DKFZ) and Federal Ministry of Education and
      Research (BMMF) (Germany); Ministry of Health and Social Solidarity, Stavros
      Niarchos Foundation and Hellenic Health Foundation (Greece); Italian Association
      for Research on Cancer (AIRC) and National Research Council (Italy); Dutch
      Ministry of Public Health, Welfare and Sports (VWS), Netherlands Cancer Registry
      (NKR), LK Research Funds, Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek
      Nederland), World Cancer Research Fund (WCRF), Statistics Netherlands (The
      Netherlands); ERC-2009-AdG 232997 and Nordforsk, Nordic Centre of Excellence
      programme on Food, Nutrition and Health (Norway); Health Research Fund (FIS),
      Regional Governments of Andalucia, Asturias, Basque Country, Murcia (no. 6236)
      and Navarra, ISCIII RETIC (RD06/0020) (Spain); Swedish Cancer Society, Swedish
      Scientific Council and Regional Government of Skane and Vasterbotten (Sweden);
      Cancer Research UK, Medical Research Council, Stroke Association, British Heart
      Foundation, Department of Health, Food Standards Agency, and Wellcome Trust (UK).
      None of the authors reported a conflict of interest.

PMID- 25779699
TI  - Twenty-four-hour monitoring of scrotal temperature in obese men and men with a
      varicocele as a mirror of spermatogenic function.
AB  - STUDY QUESTION: How do day and night scrotal temperatures, spermatogenesis
      parameters, sex hormones and intratesticular perfusion in obese men and men with
      a varicocele compare with healthy controls? SUMMARY ANSWER: Compared with healthy
      controls, 24-h monitoring of scrotal temperature in men with a varicocele and
      obese men showed higher temperatures and this condition was related to a
      significant alteration of spermatogenesis and stasis of testicular perfusion.
      WHAT IS KNOWN ALREADY: Several studies have shown that increased scrotal
      temperature has dramatic effects on spermatogenesis. Scrotal hyperthermia by
      exposure to sauna is able to induce a significant alteration of sperm production.
      STUDY DESIGN, SIZE AND DURATION: In a case-control study, data were collected
      over a period of 2 years from 60 subjects with risk factors for testicular
      heating and 20 healthy subjects who consecutively attended an andrology unit as
      participants in an infertility prevention program. PARTICIPANTS/MATERIALS,
      SETTING AND METHODS: Forty subjects with a left varicocele, 20 obese men and 20
      healthy subjects who served as controls, were evaluated for testicular volumes,
      sex hormones, sperm parameters, sperm aneuploidies, mean transit time (MTT) of
      intratesticular blood and 24-h scrotal temperature monitoring by a cutaneous
      thermochip. Subjects with a varicocele were further subgrouped on the basis of
      normo or oligozoospermia (VN and VO). Student's t-test was used for statistical
      analysis. MAIN RESULTS AND THE ROLE OF CHANCE: We found a significant increase in
      24-h mean scrotal temperature in obese men and men with a varicocele compared
      with controls (both P < 0.01). This increase in scrotal temperature was
      associated with impaired sperm parameters and higher FSH plasma levels compared
      with controls. Dynamic evaluation of scrotal temperatures showed wide
      fluctuations in controls, but little variation in obese men and men with a
      varicocele. Men with VO had left and right increase in scrotal temperatures (the
      right was increased also versus VN, P < 0.01) (both P < 0.001). Men with VN
      showed a left scrotal temperature higher than controls (P < 0.01) and a right
      scrotal temperature no different from controls (34.92 +/- 0.53 and 34.66 +/-
      0.65, respectively). Mean MTT values recorded in men with VO were significantly
      higher than men with VN and obese men (both P < 0.001). LIMITATIONS AND REASONS
      FOR CAUTION: Different lifestyle, diet, occupation, stress level and
      environmental temperatures due to seasonal conditions are major limitations of
      this study. WIDER IMPLICATIONS OF THE FINDINGS: Our data suggested for the first
      time that dynamic evaluation of scrotal temperatures seems to reflect alterations
      of testicular function and perfusion in obese men and men with a varicocele. In
      these clinical conditions, spermatogenic impairment and scrotal heating seem to
      be related to different mechanisms. The dynamic evaluation of scrotal temperature
      in subjects with risk factors for testicular heating could allow the
      identification of subjects needing treatment or a change in lifestyle. STUDY
      FUNDING/COMPETING INTERESTS: No external funding was sought for this study, and
      the authors have no conflict of interest to declare.

PMID- 25779700
TI  - Suppression of tubulin detyrosination by parthenolide recruits the plant-specific
      kinesin KCH to cortical microtubules.
AB  - Detyrosination of alpha-tubulin seems to be conserved in all eukaryotes. However,
      its biological function in plants has remained obscure. A conserved C-terminal
      tyrosine is removed by a still unidentified tubulin-tyrosine carboxypeptidase
      (TTC) and can be religated by a tubulin-tyrosine ligase (TTL). To obtain insight
      into the still elusive biological function of this detyrosination-tyrosination
      cycle, the effects of the TTC inhibitor parthenolide were analysed in BY-2
      tobacco cells. Parthenolide caused a depletion of detyrosinated alpha-tubulin,
      whereas the level of tyrosinated tubulin was elevated. This biochemical effect
      was accompanied by growth inhibition in cycling BY-2 cells and alteration of
      microtubule-dependent events that define division and expansion geometry such as
      cell plate alignment or axial expansion. Furthermore, parthenolide triggered an
      apoplastic alkalinization indicative of activation of defence-related calcium
      influx channels. At the same time, parthenolide promoted the association of the
      plant-specific kinesin KCH with cortical microtubules. These observations are
      integrated into a working model, where detyrosination acts as signal to modulate
      the binding of kinesin motors involved in structural and sensory functions of the
      microtubular cytoskeleton. 

PMID- 25779701
TI  - Overexpression of GmERF5, a new member of the soybean EAR motif-containing ERF
      transcription factor, enhances resistance to Phytophthora sojae in soybean.
AB  - Phytophthora root and stem rot of soybean [Glycine max (L.) Merr.], caused by
      Phytophthora sojae Kaufmann and Gerdemann, is a destructive disease throughout
      the soybean planting regions in the world. Here, we report insights into the
      function and underlying mechanisms of a novel ethylene response factor (ERF) in
      soybean, namely GmERF5, in host responses to P. sojae. GmERF5-overexpressing
      transgenic soybean exhibited significantly enhanced resistance to P. sojae and
      positively regulated the expression of the PR10, PR1-1, and PR10-1 genes.
      Sequence analysis suggested that GmERF5 contains an AP2/ERF domain of 58 aa and a
      conserved ERF-associated amphiphilic repression (EAR) motif in its C-terminal
      region. Following stress treatments, GmERF5 was significantly induced by P.
      sojae, ethylene (ET), abscisic acid (ABA), and salicylic acid (SA). The activity
      of the GmERF5 promoter (GmERF5P) was upregulated in tobacco leaves with ET, ABA,
      Phytophthora nicotianae, salt, and drought treatments, suggesting that GmERF5
      could be involved not only in the induced defence response but also in the ABA
      mediated pathway of salt and drought tolerance. GmERF5 could bind to the GCC-box
      element and act as a repressor of gene transcription. It was targeted to the
      nucleus when transiently expressed in Arabidopsis protoplasts. GmERF5 interacted
      with a basic helix-loop-helix transcription factor (GmbHLH) and eukaryotic
      translation initiation factor (GmEIF) both in yeast cells and in planta. To the
      best of our knowledge, GmERF5 is the first soybean EAR motif-containing ERF
      transcription factor demonstrated to be involved in the response to pathogen
      infection. 

PMID- 25779702
TI  - The impact of chronic endurance and resistance training upon the right
      ventricular phenotype in male athletes.
AB  - OBJECTIVES: The traditional view of differential left ventricular adaptation to
      training type has been questioned. Right ventricular (RV) data in athletes are
      emerging but whether training type mediates this is not clear. The primary aim of
      this study was to evaluate the RV phenotype in endurance- vs. resistance-trained
      male athletes. Secondary aims included comparison of RV function in all groups
      using myocardial speckle tracking, and the impact of allometric scaling on RV
      data interpretation. METHODS: A prospective cross-sectional design assessed RV
      structure and function in 19 endurance-trained (ET), 21 resistance-trained (RT)
      and 21 sedentary control subjects (CT). Standard 2D tissue Doppler imaging and
      speckle tracking echocardiography assessed RV structure and function. Indexing of
      RV structural parameters to body surface area (BSA) was undertaken using
      allometric scaling. RESULTS: A higher absolute RV diastolic area was observed in
      ET (mean +/- SD: 27 +/- 4 cm(2)) compared to CT (22 +/- 4 cm(2); P < 0.05) that
      was maintained after scaling. Whilst absolute RV longitudinal dimension was
      greater in ET (88 +/- 9 mm) than CT (81 +/- 10 mm; P < 0.05), this difference was
      removed after scaling. Wall thickness was not different between ET and RT and
      there were no between group differences in global or regional RV function.
      CONCLUSION: We present some evidence of RV adaptation to chronic ET in male
      athletes but limited structural characteristics of an athletic heart were
      observed in RT. Global and regional RV functions were comparable between groups.
      Allometric scaling altered data interpretation in some variables.

PMID- 25779703
TI  - Reduction of T antigen causes loss of hematopoietic progenitors in Drosophila
      through the inhibition of filopodial extensions from the hematopoietic niche.
AB  - Hematopoietic stem cells (HSCs) are present in hematopoietic organs and
      differentiate into mature blood cells as required. Defective HSCs have been
      implicated in the human autoimmune disease Tn syndrome, which results from the
      failure of the core 1 beta1,3-galactosyltransferase 1 enzyme (C1beta3GalT1) to
      synthesize T antigen. In both mice and humans, a reduced level of T antigen is
      associated with a reduction in blood cell numbers. However, the precise roles of
      T antigen in hematopoiesis are unknown. Here, we show that the Drosophila T
      antigen, supplied by plasmatocytes, is essential for the regulation of HSCs. T
      antigen appears to be an essential factor in maintaining the extracellular
      environment to support filopodial extensions from niches that are responsible for
      transmitting signaling molecules to maintain the HSCs. In addition, our results
      revealed that the clotting factor, hemolectin, disrupted the hemolymph
      environment of C1beta3GalT1 mutants. This study identified a novel mucin function
      for the regulation of HSCs that may be conserved in other species. 

PMID- 25779705
TI  - Therapeutic evaluation of interleukin 1-beta antagonist Anakinra against
      traumatic brain injury in rats.
AB  - BACKGROUND: The aim of this study was to evaluate the therapeutic efficiency of
      Anakinra, an IL-1beta antagonist with anti-inflammatory effects, in an
      experimental model of traumatic brain injury (TBI). METHODS: Fifty-four rats
      underwent TBI after a weighted object was dropped onto a metal disc secured to
      their skulls. Animals were randomized into 3 main groups: control (n=18), TBI +
      saline (n=18; six animals per time-point) with samples obtained at the first,
      sixth and twenty-fourth h postoperatively, and TBI + Anakinra (n=18; six animals
      per time-point) with brain samples obtained at the first, sixth and twenty-fourth
      h postoperatively. Brain tissue and blood serum were extracted for the analysis
      of IL-1beta, malondialdehyde, glutathione peroxidase, superoxide dismutase, and
      catalase levels. Tissue sections were evaluated histopathologically under a light
      microscope. RESULTS: After trauma, tissue and serum IL-1beta levels were
      significantly elevated and after Anakinra administration, these levels
      substantially decreased. Glutathione peroxidase, superoxide dismutase, and
      catalase activity decreased following TBI and Anakinra administration proved
      effective in increasing the activity of these antioxidant enzymes.
      Histopathological analysis confirmed that Anakinra might protect the brain tissue
      and nerve cells from injury. CONCLUSION: Results demonstrate that Anakinra
      reduces the development of inflammation and tissue injury events associated with
      TBI.

PMID- 25779704
TI  - Origin and development of neuropil glia of the Drosophila larval and adult brain:
      Two distinct glial populations derived from separate progenitors.
AB  - Glia comprise a conspicuous population of non-neuronal cells in vertebrate and
      invertebrate nervous systems. Drosophila serves as a favorable model to elucidate
      basic principles of glial biology in vivo. The Drosophila neuropil glia (NPG),
      subdivided into astrocyte-like (ALG) and ensheathing glia (EG), extend reticular
      processes which associate with synapses and sheath-like processes which surround
      neuropil compartments, respectively. In this paper we characterize the
      development of NPG throughout fly brain development. We find that differentiated
      neuropil glia of the larval brain originate as a cluster of precursors derived
      from embryonic progenitors located in the basal brain. These precursors undergo a
      characteristic migration to spread over the neuropil surface while
      specifying/differentiating into primary ALG and EG. Embryonically-derived primary
      NPG are large cells which are few in number, and occupy relatively stereotyped
      positions around the larval neuropil surface. During metamorphosis, primary NPG
      undergo cell death. Neuropil glia of the adult (secondary NPG) are derived from
      type II lineages during the postembryonic phase of neurogliogenesis. These
      secondary NPG are much smaller in size but greater in number than primary NPG.
      Lineage tracing reveals that both NPG subtypes derive from intermediate neural
      progenitors of multipotent type II lineages. Taken together, this study reveals
      previously uncharacterized dynamics of NPG development and provides a framework
      for future studies utilizing Drosophila glia as a model. 

PMID- 25779706
TI  - Effects of alpha lipoic acid on intra-abdominal adhesion: an experimental study
      in a rat model.
AB  - BACKGROUND: This study was performed to determine the effect of alpha lipoic
      acid, a powerful antioxidant, on intra-abdominal adhesion formation. METHODS:
      Twenty-four female Wistar Albino rats weighing 250-300 g were used in this study
      conducted on three groups consisting of the alpha lipoic acid group (Group I,
      n=8), control group (Group II, n=8), and sham group (Group III, n=8). After
      performing laparotomy with a midline incision under general anesthesia, the
      adhesion model was created on the antimesenteric side of the caecum in Group I
      and Group II. 50 mg/kg alpha-lipoic acid was administered intraperitoneally (IP)
      in Group I while the surgical procedure was performed but no drugs administered
      in Group II. Only laparotomy was performed in Group III. Rats were sacrificed at
      the end of the tenth day. RESULTS: Macroscopic scoring was performed, tissue
      samples were obtained and subjected to biochemical and histopathological
      evaluation. The degree of adhesion and malondialdehyde level decreased (p<0.01),
      and glutathione levels had increased (p<0.01) in Group I compared to Group II in
      macroscopic scoring. CONCLUSION: Alpha lipoic acid was found to significantly
      decrease (p<0.01) intra-abdominal adhesion when administered IP compared to the
      control group.

PMID- 25779707
TI  - Spontaneous regeneration capacity of controlled small bowel perforations: an
      experimental study in rats.
AB  - BACKGROUND: Selective observation method has started to replace routine
      laparotomy application for abdominal penetrating trauma patients after Shaftan's
      selective observation method applied in the 1960s. In this respect, there is a
      possibility of bowel perforations healing without operations. An experimental
      model was established in this study in order to clarify this possibility.
      METHODS: Fifty Wistar-Albino rats were divided into five groups, ten in each.
      While one group served as the control, distal part of the small bowel of the rats
      in the other four groups was perforated 1, 2, 3, and 4 mm in diameter with
      appropriate cutters. After a week of observation, test rats were sacrificed and
      relaparotomy was applied. The test material consisting of the perforated bowel,
      covering 1 cm of proximal and distal margins, and some peritoneal tissue was
      taken for histopathological examination. RESULTS: Small bowel perforations with a
      diameter of 2 mm or below healed spontaneously without any operation. Peritonitis
      intensity increased in direct ratio with perforation diameters. Wall repair
      capacity of the bowel diminished with increasing perforation diameters.
      CONCLUSION: It was observed that small perforations in the small bowel of rats
      could be limited by the organism itself without a necessity of any surgical
      intervention.

PMID- 25779708
TI  - Comparison of morphine-midazolam versus morphine injection for pain relief in
      patients with limb fractures - a clinical trial.
AB  - BACKGROUND: Pain relief, using opiates as a primary choice, is an important part
      of treating limb fractures. Yet, in order to reduce opiate consumption, other
      combinations have been introduced. This study aimed to compare pain reduction by
      a combination of morphine-midazolam with morphine injection in patients with limb
      fractures. METHODS: A randomized double-blind study of patients with upper or
      lower extremity fractures was conducted. Patients' response to treatment with
      either morphine-midazolam solution or morphine at 15, 30, 45, 60, 120, and 180
      minutes were assessed. The Kaplan-Meier curves and generalized estimating
      equations were examined to evaluate the success of treatment. RESULTS: A total of
      seventy-two patients aged 18-60 (80.6% male; mean age: 35+/-17.9 years) were
      included. At 15, 30, 45, and 60 minutes, successful pain control was seen in 8.83
      22.2%, 33.3% and 63.9% of the patients in the morphine group, and 11.1%, 27.7%,
      44.4% and 63.8% in the midazolam-morphine group. By the third hour, pain-control
      was achieved in all patients receiving morphine while pain persisted in one
      patient receiving morphine-midazolam. Log-rank test showed no significant
      difference between the two groups (p=0.55). CONCLUSION: Our findings revealed
      that adding midazolam to morphine did not improve its pain-relief profile.

PMID- 25779709
TI  - Outpatient burn management and unnecessary referrals.
AB  - BACKGROUND: This study aimed to determine the profile of burn patients presented
      in our polyclinic and evaluate the current status in comparison to the treatment
      methods of past series. METHODS: Burn patients presented in the polyclinic in a
      one-year period were included into this prospective study. The records of all
      patients were examined in respect of gender, age, burn percentage, burn location,
      cause of burn, degree of burn, dressing material, number of dressings, type of
      treatment, place of trauma, and month of trauma. RESULTS: From a total of one
      thousand seven hundred and ninety-five patients presented, management was
      completed in the polyclinic for one thousand five hundred and eleven cases with a
      mean age of 27.9 years, with a female: male ratio of 0.88. While most patients
      were in the 18-64 age group, hot liquid burn was the leading cause in all age
      groups (p<0.05, p<0.001). Of the total patients, 89.6% were injured at home
      (p<0.001). The extremities were determined as the body area most often burned
      (p<0.001). While a single dressing was applied to 446 patients (29.5%), in 64.9%
      of cases polyclinic follow-up was terminated after the first 3 dressings. The
      mean number of dressings was greater in patients with deep dermal burns (mean
      14.5, median 14, p<0.001). CONCLUSION: A higher incidence of burns was found due
      to increasing urban populations compared to previous years. Currently, the
      majority of patients are referred to a healthcare facilty near their residences
      for follow-up after a few dressings. Unneccessary presentation at specialist
      centres increases the workload of these centres and creates a burden of wasted
      time and transport expense for the patients. The application of current burn
      treatment principles in primary and secondary health facilities will reduce the
      workload of reference centres.

PMID- 25779710
TI  - Mortality risk factors in burn care units considering the clinical significance
      of acinetobacter infections.
AB  - BACKGROUND: This study aimed to evaluate risk factors and the role of
      Acinetobacter isolates in mortality due to burns since morbidity and mortality
      rates are considerably high. METHODS: A total of four hundred and sixty-five
      patients hospitalized in our Burn Care Unit between January 2009 and May 2011
      were reviewed retrospectively. Logistic regression analysis was used in order to
      predict the risk. RESULTS: Mortality rates were as follows: 7.5% in general, 3.9%
      for under 17 years of age, 12% for between 18-64 years of age, and 24% for over
      65 years of age (p<0.001). CONCLUSION: As the burnt body surface area increased,
      higher mortality rates were detected. Despite higher mortality rates,
      Acinetobacter infections were not found risk factors for mortality.

PMID- 25779711
TI  - Evaluation of serum L-FABP levels in patients with acute pancreatitis.
AB  - BACKGROUND: The aim of this study was to assess the serum L-FABP levels in
      patients with acute pancreatitis and compare with healthy subjects. METHODS:
      Thirty patients with acute pancreatitis and thirty consecutive healthy age- and
      sex-matched control subjects were included into the study. The serum levels of L
      FABP were measured upon admission and at the remission period. RESULTS: Upon
      admission, serum L-FABP concentration was significantly higher in patients with
      acute pancreatitis compared to control subjects (41009.41 +/- 32401.31 pg/ml vs.
      17057.00 +/- 5015.74 pg/ml, p=0.008). Serum L-FABP levels decreased after the
      remission period; however, the differences were not statistically significant. In
      addition, serum L-FABP levels showed significant correlation with AST and LDH
      levels. CONCLUSION: Increased serum L-FABP levels may be related to the mechanism
      of pancreatic microcirculatory disturbance in patients with acute pancreatitis,
      suggesting that serum L-FABP could be used for a potential biomarker of acute
      pancreatitis.

PMID- 25779712
TI  - Factors affecting postoperative mortality in patients older than 65 years
      undergoing surgery for hip fracture.
AB  - BACKGROUND: The aim of this study was to determine the factors affecting
      postoperative mortality in patients older than 65 years of age undergoing surgery
      for hip fracture. METHODS: A total of 308 patients (219 males and 89 females)
      were included into the study. Spinal-epidural anaesthesia was administered in 203
      patients and general anaesthesia in 105 patients. In the evaluation of the
      patients regarding ASA, two groups were determined ASA 1-2 and ASA 3-4. Systemic
      diseases present in the patients were determined preoperatively. RESULTS: Seventy
      seven (25%) of the total 308 patients died. In addition, patients with
      preoperative cardiac disease, patients on whom general anaesthesia was
      administered, patients in the ASA 3-4 group, and age were found to be
      significantly higher in mortality. When logistic regression analysis was
      performed for these four efficient factors, age, general anaesthesia, presence of
      cardiac disease were effective in mortality. However, ASA score changed depending
      on the age and cardiac disease. CONCLUSION: In case of presence of multiple risk
      factors, it is necessary to determine which factor is, in fact, more effective.
      Age, ASA score, type of anaesthesia, and presence of cardiac disease are
      effective in mortality. However, ASA score affects mortality depending on the
      cardiac disease and age.

PMID- 25779713
TI  - Evaluation of power Doppler sonography in acute cholecystitis to predict
      intraoperative findings: a prospective clinical study.
AB  - BACKGROUND: This study aimed to evaluate the diagnostic value of gray-scale and
      power Doppler sonography for acute cholecystitis and show a correlation between
      sonographic and intraoperative findings, quantitively. METHODS: Forty chronic and
      forty acute cholecystitis patients were examined. Early laparoscopic
      cholecystectomy was performed for acute cholecystitis. Demographic
      characteristics, sonographic findings, and adhesion scores were analyzed. Data
      were collected prospectively (clinicaltrials.gov: NCT02156947). RESULTS: Wall
      thickness (>=3 mm) and vascularity increased in acute cholecystitis (p<0.01 and
      <0.01). Vascularity was found to be moderately correlated with adhesion (p<0.01,
      r=0.59) but it did not affect the difficulty of the operation by means of
      perforation, conversion rate, and operation time. In addition, wall thickness did
      not correlate with adhesion formation (p=0.36). Sensitivity and specifity of wall
      thickness and vascularity were found to be 96.9%, 72.7%, and 68%, 87.2%,
      respectively. When both diagnostic measurements were taken into account,
      sensitivity was calculated 69.7% and specificity reached up to 97.6%. CONCLUSION:
      Vascularity correlated with adhesion but failed to predict operation difficulty.
      Specificity of gray-scale sonography could be improved with power Doppler
      examination; however, desired diagnostic accuracy could not be obtained with only
      quantitive measurements of sonography.

PMID- 25779714
TI  - [Investigation of prevalance and risk factors for hospital-acquired urinary tract
      infections in patients with severe burn injury].
AB  - BACKGROUND: This study aimed to investigate the prevalence and risk factors for
      hospital-acquired urinary tract infections in patients with severe burn injuries.
      METHODS: In this study, patients treated due to their burn injuries of greater
      than 20% between August 2009 and April 2012 in Bozyaka Training and Research
      Hospital Burn Center were assessed retrospectively. Sixty nine patients (30
      [43.5%] males, 39 [56.5%] females; mean age 40.1+/-16.7 years) were included into
      the study. RESULTS: DM, duration of the catheter and catheter care showed a
      statistically significant correlation with hospital-acquired urinary tract
      infections (p<0.005). DISCUSSION: A large number of hospital-acquired urinary
      tract infections are associated with urinary catheterization. In addition,
      removing urinary catheter within the shortest time possible is another issue to
      be considered for the prevention of these infections. If the catheter has to
      remain for a longer time, regular catheter care is recommended.

PMID- 25779715
TI  - Closed reduction of traumatic bilateral anterior hip dislocations with sedation:
      a case report and review of the literature.
AB  - A rare case of bilateral anterior hip dislocation reduced under sedation was
      reported in this study. A 47-year-old man was knocked down by a car and sustained
      bilateral anterior hip dislocation which was reduced successfully with sedation
      using titrated dose of intravenous Midazolam in combination with Pethidine. A
      modified Lefkowitz maneuver using the manipulator's thigh as a fulcrum was used.
      Patient started weight bearing in the second month after injury and was walking
      without any hip pain at the twenty-fourth month follow-up. Thirteen case reports
      describing bilateral anterior hip dislocations were found while reviewing the
      literature and it was noticed that only one author had reported the usage of
      intravenous sedation (Propofol) for the reduction procedure. However, no author
      reported the use of Lefkowitz maneuver for this purpose. Consequently, reduction
      of a bilateral anterior hip dislocation is possible with sedation using a
      modified Lefkowitz maneuver. 

PMID- 25779716
TI  - Carotid blowout syndrome.
AB  - Carotid blowout syndrome refers to the rupture of the carotid artery and its
      branches. Carotid blowout syndrome is a dangerous medical emergency typically
      resulting from complications of treatments for head and neck cancer. A patient
      without a prior history of head or neck cancer presented to the emergency
      department with a painless, enlarging neck mass was reported in this study. The
      mass progressed to acute airway obstruction during imaging of the lesion and
      necessitated emergency cricothyrotomy to secure the airway. The patient underwent
      four endovascular treatments to manage repeated bleeding thus producing the
      neurological complication of right middle cerebral artery infarction. Clinical
      manifestations, varied treatments, and common complications of carotid blowout
      syndrome were discussed. 

PMID- 25779717
TI  - The care of a patient with Fournier's gangrene.
AB  - Fournier's gangrene is a rare, necrotizing fasciitis of the genitals and perineum
      caused by a mixture of aerobic and anaerobic microorganisms. This infection leads
      to complications including multiple organ failure and death. Due to the
      aggressive nature of this condition, early diagnosis is crucial. Treatment
      involves extensive soft tissue debridement and broad-spectrum antibiotics.
      Despite appropriate therapy, mortality is high. This case report aimed to present
      nursing approaches towards an elderly male patient referred to the urology
      service with a diagnosis of Fournier's gangrene. 

PMID- 25779718
TI  - Late onset brachial artery thrombosis and total temporary peripheral neuropathy
      in a child with humerus supracondylar fracture: a case report.
AB  - Pediatric supracondylar fractures of the humerus are generally associated with
      neurovascular complications due to the deformity and sharp nature of bone
      fragments. When treated inadequately, these injuries may result in catastrophic
      complications, such as Volkmann's contracture and amputation. To our knowledge,
      late onset brachial arterial thrombosis and total temporary peripheral neuropathy
      after surgery of pediatric supracondylar fracture in the setting of normal
      preoperative vascular examination has not been reported yet. In this study, a 2
      year and 6- month-old girl, who had delayed brachial arterial thrombosis after a
      displaced humerus supracondylar fracture surgery treated with embolectomy, was
      reported. Total lesion of median, ulnar and radial nerves completely resolved
      four months after surgery. Close neurovascular monitoring on the postoperative
      phase especially in severely displaced supracondylar fractures is strongly
      emphasized even in the setting of well-perfused hand. 

PMID- 25779720
TI  - Cholesterol and cognitive performance among community volunteers from the Czech
      Republic.
AB  - BACKGROUND: Research shows that lipid levels may be associated with cognitive
      function, particularly among women. We aimed to examine total cholesterol (TC),
      low-density lipoprotein cholesterol (LDL-C), triglycerides (TG), high-density
      lipoprotein (HDL), and HDL/LDL ratio in relation to cognitive performance,
      measured with six well-established cognitive domains and a composite cognitive
      score (CCS). METHODS: In this cross-sectional study, biomarkers and
      neuropsychological assessment were available for 141 adults with MMSE scores >=
      24 (mean age = 69 years, 47% female, mean education = 14.4 years) attending a
      neuropsychological evaluation. Ordinary least squares regressions were adjusted
      for age, gender, education, and depressive symptoms in Model 1 and also for
      apolipoprotein E4 (APOE4) status in Model 2. RESULTS: High-density lipoprotein
      cholesterol (HDL-C) was associated with better CCS (beta = 0.24; p = 0.014). This
      association was significant among women (beta = 0.30; p = 0.026) and not among
      men (beta = 0.20; p = 0.124). HDL-C was also related to attention/working memory
      (beta = 0.24; p = 0.021), again only among women (beta = 0.37; p = 0.012) and not
      men (beta = 0.15; p = 0.271). Adjusting for APOE4 yielded significance for high
      HDL-C and CCS (beta = 0.24; p = 0.022). CONCLUSIONS: HDL-C was the main
      lipoprotein affecting cognitive function, with results somewhat more pronounced
      among women. Research should investigate the possibility of finding ways to boost
      HDL-C levels to potentially promote cognitive function.

PMID- 25779719
TI  - Role of Sleep Disturbance, Depression, Obesity, and Physical Inactivity in
      Fatigue in Rheumatoid Arthritis.
AB  - OBJECTIVE: Fatigue is a major concern for individuals with rheumatoid arthritis
      (RA). However, in order to treat fatigue adequately, its sources need to be
      identified. METHODS: Data were collected during a single home visit (number of
      participants = 158). All participants had physician-diagnosed RA. Assessments of
      self-reported sleep quality, depression, physical activity, RA disease activity,
      muscle strength, functional limitations, and body composition were made.
      Information on demographics, medications, and smoking was collected. The Fatigue
      Severity Inventory (FSI; measuring average fatigue over the past 7 days) was used
      as the primary outcome. Analyses were first conducted to evaluate bivariate
      relationships with fatigue. Correlations among risk factors were examined.
      Multivariate analyses identified independent predictors of fatigue. RESULTS: The
      mean +/- SD age was 59 +/- 11 years, the mean +/- SD disease duration was 21 +/-
      13 years, and 85% of subjects were female. The mean +/- SD FSI rating was 3.8 +/-
      2.0 (range 0-10). In multivariate analyses, self-reported disease activity, poor
      sleep, depression, and obesity were independently associated with fatigue.
      Physical inactivity was correlated with poor sleep, depression, and obesity.
      Mediation analyses indicated that physical inactivity had an indirect association
      with fatigue, mediated by poor sleep, depression, and obesity. CONCLUSION: This
      cross-sectional study suggests that fatigue may not be solely a result of RA
      disease activity, but may result from a constellation of factors that includes RA
      disease activity or pain, but also includes inactivity, depression, obesity, and
      poor sleep. The results suggest new avenues for interventions to improve fatigue
      in individuals with RA, such as increasing physical activity or addressing
      depression or obesity.

PMID- 25779721
TI  - A novel method for delineation of oral mucosa for radiotherapy dose-response
      studies.
AB  - There is currently no standard method for delineating the oral mucosa and most
      attempts are oversimplified. A new method to obtain anatomically accurate
      contours of the oral mucosa surfaces was developed and applied to 11 patients.
      This is expected to represent an opportunity for improved toxicity modelling of
      oral mucositis. 

PMID- 25779722
TI  - Accuracy of applicator tip reconstruction in MRI-guided interstitial 192Ir-high
      dose-rate brachytherapy of liver tumors.
AB  - BACKGROUND AND PURPOSE: To evaluate the reconstruction accuracy of brachytherapy
      (BT) applicators tips in vitro and in vivo in MRI-guided (192)Ir-high-dose-rate
      (HDR)-BT of inoperable liver tumors. MATERIALS AND METHODS: Reconstruction
      accuracy of plastic BT applicators, visualized by nitinol inserts, was assessed
      in MRI phantom measurements and in MRI (192)Ir-HDR-BT treatment planning datasets
      of 45 patients employing CT co-registration and vector decomposition.
      Conspicuity, short-term dislocation, and reconstruction errors were assessed in
      the clinical data. The clinical effect of applicator reconstruction accuracy was
      determined in follow-up MRI data. RESULTS: Applicator reconstruction accuracy was
      1.6+/-0.5 mm in the phantom measurements. In the clinical MRI datasets applicator
      conspicuity was rated good/optimal in ?72% of cases. 16/129 applicators showed
      not time dependent deviation in between MRI/CT acquisition (p>0.1).
      Reconstruction accuracy was 5.5+/-2.8 mm, and the average image co-registration
      error was 3.1+/-0.9 mm. Vector decomposition revealed no preferred direction of
      reconstruction errors. In the follow-up data deviation of planned dose
      distribution and irradiation effect was 6.9+/-3.3 mm matching the mean co
      registration error (6.5+/-2.5 mm; p>0.1). CONCLUSION: Applicator reconstruction
      accuracy in vitro conforms to AAPM TG 56 standard. Nitinol-inserts are feasible
      for applicator visualization and yield good conspicuity in MRI treatment planning
      data. No preferred direction of reconstruction errors were found in vivo.

PMID- 25779723
TI  - Canonical autophagy does not contribute to cellular radioresistance.
AB  - BACKGROUND: (Pre)clinical studies indicate that autophagy inhibition increases
      response to anti-cancer therapies. Although promising, due to contradicting
      reports, it remains unclear if radiation therapy changes autophagy activity and
      if autophagy inhibition changes the cellular intrinsic radiosensitivity.
      Discrepancies may result from different assays and models through off-target
      effects and influencing other signaling routes. In this study, we directly
      compared the effects of genetic and pharmacological inhibition of autophagy after
      irradiation in human cancer cell lines. MATERIALS AND METHODS: Changes in
      autophagy activity after ionizing radiation (IR) were assessed by flux analysis
      in eight cell lines. Clonogenic survival, DNA damage (COMET-assay) and H2AX
      phosphorylation were assessed after chloroquine or 3-methyladenine pretreatment
      and after ATG7 or LC3b knockdown. RESULTS: IR failed to induce autophagy and
      chloroquine failed to change intrinsic radiosensitivity of cells. Interestingly,
      3-methyladenine and ATG7- or LC3b-deficiency sensitized cancer cells to
      irradiation. Surprisingly, the radiosensitizing effect of 3-methyladenine was
      also observed in ATG7 and LC3b deficient cells and was associated with attenuated
      gamma-H2AX formation and DNA damage repair. CONCLUSION: Our data demonstrate that
      the anti-tumor effects of chloroquine are independent of changes in intrinsic
      radioresistance. Furthermore, ATG7 and LC3b support radioresistance independent
      of canonical autophagy that involves lysosomal degradation.

PMID- 25779724
TI  - Unravelling "off-target" effects of redox-active polymers and polymer
      multilayered capsules in prostate cancer cells.
AB  - Redox-active polymers and carriers are oxidizing nanoagents that can potentially
      trigger intracellular off-target effects. In the present study, we investigated
      the occurrence of off-target effects in prostate cancer cells following exposure
      to redox-active polymer and thin multilayer capsules with different chemical
      properties. We show that, depending on the intracellular antioxidant capacity,
      thiol-functionalized poly(methacrylic acid), PMA(SH) triggers cell defense
      responses/perturbations that result in off-target effects (i.e., induction of
      autophagy and down-regulation of survivin). Importantly, the conversion of the
      carboxyl groups of PMA(SH) into the neutral amides of
      poly(hydroxypropylmetacrylamide) (pHPMA(SH)) nullified the off-target effects and
      cytotoxicity in tested cell lines. This suggests that the simultaneous action of
      carboxyl and disulfide groups in PMA(SH) polymer or capsules may play a role in
      mediating the intracellular off-target effects. Our work provides evidence that
      the rational design of redox-active carriers for therapeutic-related application
      should be guided by a careful investigation on potential disturbance of the
      cellular machineries related to the carrier association.

PMID- 25779725
TI  - Complex watersheds, collaborative teams: Assessing pollutant presence and effects
      in the San Francisco Delta.
AB  - There is a great diversity of sources of chemical contaminants and stressors over
      large geographic areas. Chemical contaminant inputs and magnitude can potentially
      exhibit wide seasonal variation over large geographic areas. Together, these
      factors make linking exposure to monitored chemical contaminants and effects
      difficult. In practice, this linkage typically relies on relatively limited
      chemical occurrence data loosely coupled with individual effects, and population-
      or community-level assessments. Increased discriminatory power may be gained by
      approaching watershed level assessment in a more holistic manner, drawing from a
      number of disciplines that target endpoints spanning levels of the biological
      hierarchy. Using the Sacramento River as a case study, the present study aimed to
      1) evaluate the performance of new analytical and biomarker tools in a real world
      setting and their potential for linking occurrence and effect; 2) characterize
      the effects of geographic and temporal variability through the integration of
      suborganismal, tissue, and individual level endpoints, as well as extensive
      chemical analyses; 3) identify knowledge gaps and research needs that limit the
      implementation of this holistic approach; and 4) provide an experimental design
      workflow for these types of assessments. Sites were selected to target inputs
      into the Sacramento River as it transitions from an agricultural to a mixed but
      primarily urban landscape. Chemical analyses were conducted on surface water
      samples at each site in both the spring and fall for pesticides, hormones, and
      active pharmaceutical ingredients (APIs). Active pharmaceutical ingredients were
      more often detected across sampling events in the fall; however, at the most
      downstream site the number of analytes detected and their concentrations were
      greater in the spring, which may be due to seasonal differences in rainfall.
      Changes in gene and protein expression targeting endocrine and reproductive
      effects were observed within each sampling event; however, they were inconsistent
      across seasons. Larval mortality at the most downstream site was seen in both
      seasons; however, behavioral changes were only observed in the spring. No clear
      linkages of specific analyte exposure to biological response were observed, nor
      were linkages across biological levels of organization. This failure may have
      resulted from limitations of the scope of molecular endpoints used, inconsistent
      timing of exposure, or discordance of analytical chemistry through grab sampling
      and longer term, integrative exposure. Together, results indicate a complicated
      view of the watershed.

PMID- 25779748
TI  - Lessons from 150 years of UK maternal hemorrhage deaths.
AB  - We have reviewed maternal hemorrhage death rates in the UK over the past 150
      years in order to draw lessons from this material for current attempts to reduce
      global maternal mortality. Mortality rates from data in the UK Annual Reports
      from the Registrar General were entered into a database. Charts were created to
      display trends in hemorrhage mortality, allowing comparison with historical
      medical advances. Hemorrhage death rates fell steadily before the 1930s; between
      1874 and 1926 they fell by 56%. In contrast, there was no consistent reduction in
      overall maternal mortality rates until the 1930s; from 1932 to 1952 they fell by
      85%, primarily due to a reduction in sepsis deaths. In conclusion the majority of
      maternal hemorrhage mortality reductions in the UK occurred prior to the
      availability of effective oxytocics, antibiotics, and blood transfusion.
      Improving access to and standards of maternal care is key to addressing global
      maternal mortality today.

PMID- 25779749
TI  - Nano-sized Mn3O4 and beta-MnOOH from the decomposition of beta-cyclodextrin-Mn:
      2. The water-oxidizing activities.
AB  - Nano-sized Mn oxides contain Mn3O4, beta-MnOOH and Mn2O3 have been prepared by a
      previously reported method using thermal decomposition of beta-cyclodextrin-Mn
      complexes. In the next step, the water-oxidizing activities of these Mn oxides
      using cerium(IV) ammonium nitrate as a chemical oxidant are studied. The turnover
      frequencies for beta-MnO(OH) and Mn3O4 are 0.24 and 0.01-0.17 (mmol O2/mol Mns),
      respectively. Subsequently, water-oxidizing activities of these compounds are
      compared to the other previously reported Mn oxides. Important factors affecting
      water oxidation by these Mn oxides are also discussed. 

PMID- 25779751
TI  - Prior publication of papers.

PMID- 25779750
TI  - Apremilast in Patients With Active Rheumatoid Arthritis: A Phase II, Multicenter,
      Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Study.
AB  - OBJECTIVE: To study the efficacy/safety of apremilast, an oral phosphodiesterase
      4 inhibitor, compared with placebo in patients with active rheumatoid arthritis
      (RA) who had an inadequate response to methotrexate (MTX). METHODS: Patients were
      randomized 1:1:1 to receive placebo, apremilast 20 mg twice a day, or apremilast
      30 mg twice a day. Patients whose swollen and tender joint counts had not
      improved by >=20% were considered nonresponders at week 16 and were required to
      enter the protocol-defined early escape. At week 24, patients were transitioned
      in a blinded manner to receive apremilast 20 mg twice a day if they were
      initially randomized to receive placebo. Patients who were not initially
      randomized to receive placebo continued to receive their target apremilast dose.
      Patients were required to take a stable dose of MTX (7.5-25 mg/week) throughout
      the study. Magnetic resonance imaging (MRI) was performed in a subset of
      patients. RESULTS: A total of 237 patients who were receiving MTX therapy were
      randomized and received >=1 dose of study medication. At week 16, similar
      proportions of patients receiving placebo (35%), apremilast 20 mg twice a day
      (28%), and apremilast 30 mg twice a day (34%) met the American College of
      Rheumatology criteria for 20% improvement in disease activity (the primary
      efficacy end point). In the MRI substudy, mean change from baseline in total
      joint damage scores according to the Rheumatoid Arthritis Magnetic Resonance
      Imaging Scoring system was generally similar with either apremilast dose at week
      16. At week 52, no trends were noted for clinical end points by treatment group.
      Both apremilast doses were generally well tolerated. CONCLUSION: Apremilast
      efficacy was not demonstrated in patients who had active RA despite stable MTX
      therapy.

PMID- 25779752
TI  - Cardiovascular pathobiology of inflammasomes: inflammatory machinery and beyond.
AB  - SIGNIFICANCE: In response to infection or cellular stress, inflammasomes are
      assembled and activated to mediate host defense and to initiate or promote the
      development of different diseases, in particular, autoinflammatory diseases and
      chronic degenerative diseases. Understanding of inflammasomes and related
      physiological and pathological relevance to the cardiovascular system will open a
      new chapter on the pathogenesis of inflammation and related diseases and will
      help develop novel therapeutic strategies for prevention or treatment of
      cardiovascular diseases. RECENT ADVANCES: The inflammasome, in particular the
      nucleotide oligomerization domain-like receptor containing pyrin domain 3 (NLRP3)
      inflammasome, has been recently recognized as a fundamental mechanism to mediate
      or promote the pathogenesis of degenerative diseases. Some important mechanisms
      responsible for NLRP3 inflammasome activation have been proposed and many
      molecular targets associated with this inflammasome activation are shown to be
      the possible candidates of therapeutic targets for treatment of cardiovascular
      diseases. CRITICAL ISSUES: The concepts that NLRP3 inflammasome activation occurs
      just in immune cells or phagocytes and that its role is only for the inflammatory
      progression of cardiovascular diseases are oversimplified. A large body of other
      cell types are capable of NLRP3 inflammasome activation, and many uncanonical
      effects of this inflammasome may also be implicated in the development of
      cardiovascular diseases, which are discussed in a great detail by this Forum.
      FUTURE DIRECTIONS: More mechanistic and translational studies will rapidly widen
      the horizon of knowledge on NLRP3 inflammasome activation and regulation, which
      may help develop novel effective therapeutic strategies to target this
      inflammasome for treatment or prevention of cardiovascular diseases.

PMID- 25779753
TI  - Erratum to: Mitochondrial phospholipids: role in mitochondrial function.

PMID- 25779754
TI  - Thermostability and reactivity in organic solvent of O-phospho-L-serine
      sulfhydrylase from hyperthermophilic archaeon Aeropyrum pernix K1.
AB  - O-phospho-l-serine sulfhydrylase (OPSS) from archaeon Aeropyrum pernix K1 is able
      to synthesize l-cysteine even at 80  degrees C. In this article, we compared
      thermal stability and reactivity in organic solvent of OPSS with those of O
      acetyl-l-serine sulfhydrylase B (OASS-B) from Escherichia coli. As a result, the
      thermostability of OPSS was much higher than that of OASS-B. Moreover, the
      activity of OPSS increased in the reaction mixture containing the organic
      solvent, such as N, N'-dimethyl formamide and 1,4-dioxane, whereas that of OASS-B
      gradually decreased as the content of organic solvent increased. From the crystal
      structural analysis, the intramolecular electrostatic interactions of N-terminal
      domain in OPSS seemed to be correlated with the tolerance of OPSS to high
      temperature and organic solvent. These results indicate that OPSS is more
      superior to OASS-B for the industrial production of l-cysteine and unnatural
      amino acids that are useful pharmaceuticals in the presence of organic solvent.

PMID- 25779755
TI  - Repeat abortions in New York City, 2010.
AB  - This study aims to describe factors associated with the number of past abortions
      obtained by New York City (NYC) abortion patients in 2010. We calculated rates of
      first and repeat abortion by age, race/ethnicity, and neighborhood-level poverty
      and the mean number of self-reported past abortions by age, race/ethnicity,
      neighborhood-level poverty, number of living children, education, payment method,
      marital status, and nativity. We used negative binomial regression to predict
      number of past abortions by patient characteristics. Of the 76,614 abortions
      reported for NYC residents in 2010, 57% were repeat abortions. Repeat abortions
      comprised >50% of total abortions among the majority of sociodemographic groups
      we examined. Overall, mean number of past abortions was 1.3. Mean number of past
      abortions was higher for women aged 30-34 years (1.77), women with >=5 children
      (2.50), and black non-Hispanic women (1.52). After multivariable regression, age,
      race/ethnicity, and number of children were the strongest predictors of number of
      past abortions. This analysis demonstrates that, although socioeconomic
      disparities exist, all abortion patients are at high risk for repeat unintended
      pregnancy and abortion.

PMID- 25779756
TI  - Comprehensive transgender healthcare: the gender affirming clinical and public
      health model of Fenway Health.
AB  - This report describes the evolution of a Boston community health center's
      multidisciplinary model of transgender healthcare, research, education, and
      dissemination of best practices. This process began with the development of a
      community-based approach to care that has been refined over almost 20 years where
      transgender patients have received tailored services through the Transgender
      Health Program. The program began as a response to unmet clinical needs and has
      grown through recognition that our local culturally responsive approach that
      links clinical care with biobehavioral and health services research, education,
      training, and advocacy promotes social justice and health equity for transgender
      people. Fenway Health's holistic public health efforts recognize the key role of
      gender affirmation in the care and well-being of transgender people worldwide. 

PMID- 25779757
TI  - Decision support for organ offers in liver transplantation.
AB  - Organ offers in liver transplantation are high-risk medical decisions with a low
      certainty of whether a better liver offer will come along before death. We
      hypothesized that decision support could improve the decision to accept or
      decline. With data from the Scientific Registry of Transplant Recipients,
      survival models were constructed for 42,857 waiting-list patients and 28,653
      posttransplant patients from 2002 to 2008. Daily covariate-adjusted survival
      probabilities from these 2 models were combined into a 5-year area under the
      curve to create an individualized prediction of whether an organ offer should be
      accepted for a given patient. Among 650,832 organ offers from 2008 to 2013,
      patient survival was compared by whether the clinical decision was concordant or
      discordant with model predictions. The acceptance benefit (AB)--the predicted
      gain or loss of life by accepting a given organ versus waiting for the next organ
      -ranged from 3 to -22 years (harm) and varied geographically; for example, the
      average benefit of accepting a donation after cardiac death organ ranged from
      0.47 to -0.71 years by donation service area. Among organ offers, even when AB
      was >1 year, the offer was only accepted 10% of the time. Patient survival from
      the time of the organ offer was better if the model recommendations and the
      clinical decision were concordant: for offers with AB > 0, the 3-year survival
      was 80% if the offer was accepted and 66% if it was declined (P < 0.001). In
      conclusion, augmenting clinical judgment with decision support may improve
      patient survival in liver transplantation.

PMID- 25779758
TI  - Thrombosis of the hepatic veins secondary to abdominal trauma.

PMID- 25779759
TI  - Molecular orientation of lead phthalocyanine on (100) oriented single crystal
      diamond surfaces.
AB  - Lead phthalocyanine (PbPc) thin films of 5 and 50 nm have been deposited on
      hydrogen and oxygen terminated single crystal diamond (SCD) using organic
      molecular beam deposition. Atomic force microscopy and X-ray diffraction (XRD)
      studies showed that PbPc grown on the hydrogen terminated SCD forms layers with a
      high degree of crystallinity, dominated by the monoclinic (320) orientation
      parallel to the diamond surface. The oxygen terminated diamond led to a randomly
      oriented PbPc film. Absorption and photocurrent measurements indicated the
      presence of both polymorphs of PbPc, however, the ratio differed depending on the
      termination of the SCD. Finally, polarized Raman spectroscopy was used to
      determine the orientation of the molecules of the thin film. The results
      confirmed the random orientation on the O-terminated diamond. On SCD:H, the PbPc
      molecules are lying down in accordance with the XRD results. 

PMID- 25779760
TI  - Antioxidative and antiinflammatory activities of asiatic acid, glycyrrhizic acid,
      and oleanolic acid in human bronchial epithelial cells.
AB  - Protective effects of triterpenic acids, asiatic acid (AA), glycyrrhizic acid
      (GA), or oleanolic acid (OA), for two human bronchial epithelial cells, 16HBE and
      BEAS-2B cells, against hydrogen peroxide (H2O2) induced injury were examined.
      Cells were pretreated by triterpenic acid at 4 or 8 MUmol/L and followed by H2O2
      treatment. Results showed that H2O2 significantly upregulated both Bax and
      cleaved caspase-3 expression, and also downregulated Bcl-2 expression in test
      cells. AA at these doses retained Bcl-2 expression, but GA and OA only at 8
      MUmol/L reserved Bcl-2 expression. Test triterpenic acids lowered cleaved caspase
      3 expression dose-dependently. H2O2 treatment lowered Na(+)-K(+)-ATPase activity
      and mitochondrial membrane potential in cells. Triterpenic acid pretreatments
      significantly maintained mitochondrial membrane potential and Na(+)-K(+)-ATPase
      activity. H2O2 enhanced reactive oxygen species, interleukin-6, tumor necrosis
      factor-alpha, and prostaglandin E2 levels in test cells. Three triterpenic acid
      treatments dose-dependently reversed these changes. H2O2 promoted the protein
      expression of p47(phox), gp91(phox), cyclooxygenase-2 (COX-2), mitogen-activated
      protein kinase, and nuclear factor-kappaB (NF-kappaB). AA, GA, or OA
      pretreatments dose-dependently downregulated the expression of p47(phox), COX-2,
      NF-kappaB p65, and p-p38 but only at 8 MUmol/L decreased gp91(phox) expression.
      These results support that these triterpenic acids could protect bronchial
      epithelial cells to attenuate apoptotic, oxidative, and inflammatory stress.

PMID- 25779761
TI  - Expression of Heparin-Binding EGF-Like Growth Factor (HB-EGF) in Bovine
      Endometrium: Effects of HB-EGF and Interferon-tau on Prostaglandin Production.
AB  - Heparin-binding EGF-like growth factor (HB-EGF) regulates several cell functions
      by binding to its membrane receptor (ErbB1 and ErbB4). Experimental evidences
      suggest that HB-EGF, prostaglandins (PGs) and interferon-tau (IFN-tau) regulate
      uterine function for pregnancy establishment in ruminants. In this study, the
      mRNA expressions of HB-EGF, ErbB1 and ErbB4 in bovine endometrium and the effects
      of HB-EGF and IFN-tau on PGE2 and PGF2-alpha production by endometrial cells were
      investigated. RT-PCR analysis revealed that HB-EGF mRNA was greater at the mid
      luteal stage than at the early and regressed luteal stages (p < 0.05). ErbB1 mRNA
      expression was greater at the mid- and late luteal stages than at the other
      luteal stages (p < 0.05). IFN-tau increased the expression of HB-EGF, ErbB1 and
      ErbB4 mRNA in epithelial cells (p < 0.05). HB-EGF did not affect PGF2-alpha or
      PGE2 production by bovine endometrial epithelial cells, but increased PGF2-alpha
      and PGE2 production by bovine endometrial stromal cells (p < 0.05). IFN-tau
      significantly decreased HB-EGF-stimulated PGF2-alpha (p < 0.05), but not PGE2 (p
      > 0.05) production by stromal cells. These results indicate that HB-EGF and its
      receptors expression changed in bovine endometrium throughout the oestrous cycle.
      IFN-tau increased their expression in cultured endometrial cells. HB-EGF and IFN
      tau have the ability to regulate PGs production by stromal cells and therefore
      may play a role in the local regulation of uterine function at the time of
      implantation in cattle. 

PMID- 25779762
TI  - Facile and green production of aqueous graphene dispersions for biomedical
      applications.
AB  - We proposed a facile, low cost, and green approach to produce stable aqueous
      graphene dispersions from graphite by sonication in aqueous bovine serum albumin
      (BSA) solution for biomedical applications. The production of high-quality
      graphene was confirmed using microscopy images, Raman spectroscopy, UV-vis
      spectroscopy, and XPS. In addition, ab initio calculations revealed molecular
      interactions between graphene and BSA. The processability of aqueous graphene
      dispersions was demonstrated by fabricating conductive and mechanically robust
      hydrogel-graphene materials. 

PMID- 25779763
TI  - Ultrasonic evaluation of the morphological characteristics of metallic powders in
      the context of mechanical alloying.
AB  - An ultrasonic method is proposed to characterize the morphological (geometrical)
      aspects of powders through the elastic modulus dependence of their packing on the
      factors of polydispersity, coordination number and particle shape. During the
      mechanical alloying process, the variation in geometrical characteristics of
      powders provides critical information. Ultrasonic parameters are shown to be
      sensitive not only to the average contact number per bead (i.e. the coordination
      number) but also to characteristics of the bead size distribution, when given the
      same sample preparation and confining pressure. These parameters, in turn, are
      sensitive to both the granular medium polydispersity and particle shapes. A non
      monotonic behavior of the ultrasonic velocity (and of the derived compressional
      wave modulus) is observed throughout the alloying process, which thus offers
      possibilities for powder structure monitoring. 

PMID- 25779764
TI  - Post-stroke fatigue: a review on prevalence, correlates, measurement, and
      management.
AB  - BACKGROUND: Post-stroke fatigue (PSF) is a common yet debilitating symptom for
      the majority of patients post-stroke. However, limited information is available
      for the management of this disabling condition. This is partly due to our poor
      understanding of the condition. OBJECTIVES: In this paper, we review the
      prevalence, predisposing factors, impact, measurement, and management of PSF.
      RESULTS: The prevalence of PSF ranged from 29 to 70%, depending on the selected
      outcome measurement tools and the patient characteristics. Predisposing factors
      of PSF are multifactorial, including biological, physical, and psychological
      factors. Further, the relationships between some of the predisposing factors and
      PSF seem to be indirect. CONCLUSIONS: PSF has an adverse effect on the patient's
      quality of life, recovery, and mortality. Its impact on physical function and
      independence requires further investigation. There are a number of tools
      available to measure fatigue in neurological conditions. However, very few of
      them have been validated in stroke. Lastly, single-disciplinary management for
      PSF was rarely successful. In contrast, evidence suggests that approaches which
      incorporated both physical and psychological interventions may be beneficial.
      Further studies are urgently needed to gain a better understanding of the
      etiology of PSF, such that the development of better management strategies is
      possible.

PMID- 25779765
TI  - Single-carbon discrimination by selected peptides for individual detection of
      volatile organic compounds.
AB  - Although volatile organic compounds (VOCs) are becoming increasingly recognized
      as harmful agents and potential biomarkers, selective detection of the organic
      targets remains a tremendous challenge. Among the materials being investigated
      for target recognition, peptides are attractive candidates because of their
      chemical robustness, divergence, and their homology to natural olfactory
      receptors. Using a combinatorial peptide library and either a graphitic surface
      or phenyl-terminated self-assembled monolayer as relevant target surfaces, we
      successfully selected three interesting peptides that differentiate a single
      carbon deviation among benzene and its analogues. The heterogeneity of the
      designed target surfaces provided peptides with varying affinity toward targeted
      molecules and generated a set of selective peptides that complemented each other.
      Microcantilever sensors conjugated with each peptide quantitated benzene, toluene
      and xylene to sub-ppm levels in real time. The selection of specific receptors
      for a group of volatile molecules will provide a strong foundation for general
      approach to individually monitoring VOCs. 

PMID- 25779766
TI  - The multikinase inhibitor Sorafenib enhances glycolysis and synergizes with
      glycolysis blockade for cancer cell killing.
AB  - Although the only effective drug against primary hepatocarcinoma, the multikinase
      inhibitor Sorafenib (SFB) usually fails to eradicate liver cancer. Since SFB
      targets mitochondria, cell metabolic reprogramming may underlie intrinsic tumor
      resistance. To characterize cancer cell metabolic response to SFB, we measured
      oxygen consumption, generation of reactive oxygen species (ROS) and ATP content
      in rat LCSC (Liver Cancer Stem Cells) -2 cells exposed to the drug. Genome wide
      analysis of gene expression was performed by Affymetrix technology. SFB
      cytotoxicity was evaluated by multiple assays in the presence or absence of
      metabolic inhibitors, or in cells genetically depleted of mitochondria. We found
      that low concentrations (2.5-5 MUM) of SFB had a relatively modest effect on LCSC
      2 or 293 T cell growth, but damaged mitochondria and increased intracellular ROS.
      Gene expression profiling of SFB-treated cells was consistent with a shift toward
      aerobic glycolysis and, accordingly, SFB cytotoxicity was dramatically increased
      by glucose withdrawal or the glycolytic inhibitor 2-DG. Under metabolic stress,
      activation of the AMP dependent Protein Kinase (AMPK), but not ROS blockade,
      protected cells from death. We conclude that mitochondrial damage and ROS drive
      cell killing by SFB, while glycolytic cell reprogramming may represent a
      resistance strategy potentially targetable by combination therapies.

PMID- 25779767
TI  - IgG4 antibodies and peanut challenge outcome in children IgE-sensitized to
      peanut.

PMID- 25779768
TI  - Failure to Provide ABPM to All Hypertensive Patients Amounts to Medical
      Ineptitude.

PMID- 25779769
TI  - Non-uniform space charge limited current injection into a nano contact solid.
AB  - We have developed a two-dimensional (2D) non-uniform model to study the space
      charge limited (SCL) current injection into a trap-filled solid of nano-contact,
      such as organic materials and dielectrics. Assuming a solid of length D with a
      contact of width W, the enhancement over the well-known 1D uniform model is
      calculated as a function of W/D for different material properties, such as the
      dielectric constant (epsilon) and the trap distribution. The non-uniform current
      density profile due to edge effect is predicted. The findings reported here are
      different from the prior uniform 2D models, which are significant for small W/D
      when the size of the contact reaching nanometer scale, i.e. W = 50 nm for D = 1
      MUm. This model will be useful for the characterization of carrier mobility and
      properties of traps, which are critical to many novel devices (with small nano
      contact) operating in the space charge limited condition reporting in novel
      device and its applications. Empirical formulas are given for future comparison
      with experimental results.

PMID- 25779770
TI  - Molecular analysis of isolates of the cestode Rodentolepis nana from the great
      gerbil, Rhombomys opimus.
AB  - Rodentolepis nana (syn. Hymenolepis nana) is a cyclophyllidean zoonotic enteric
      parasite with worldwide distribution. In humans, it is more prevalent in
      children, especially in temperate zones. A morphologically similar species of R.
      nana occurs in different rodents, including gerbils. In the present study
      molecular characterization of five isolates of R. nana from Rhombomys opimus in
      the Golestan Province (n= 2) and Razavi Khorasan Province (n= 3), both in north
      eastern Iran, were analysed. After DNA extraction, the internal transcribed
      spacer 2 (ITS2) region of the R. nana isolates was amplified and sequenced, and
      genetic variation was analysed. Accordingly, two isolates from the Razavi
      Khorasan Province showed ITS2 signatures that differed from the isolates from the
      Golestan Province. The third isolate from Razavi Khorasan did not reveal these
      specific signatures, but exhibited sparse nucleotide polymorphisms in the ITS2
      sequence. The ITS gene is conserved, and variation in this fragment could be an
      interesting subject for further inspection of existing variation in the genome of
      R. nana, among different domestic and wildlife host species and from different
      areas.

PMID- 25779771
TI  - Aromaticity Switching in Porphyrinoids.
AB  - The aromaticity of porphyrinoids can be substantially altered by reversible
      modification of their original electronic structures. Well-defined modulators can
      be used as a means to initiate these modifications, including redox processes,
      acid-base chemistry, and conformational phenomena. This Focus Review emphasizes
      the situation for which a single macrocyclic frame alternatively adopts diatropic
      and paratropic features and both situations are readily and mutually
      exchangeable. Eventually, such a porphyrinoid transformation can be explored as a
      suitable element to construct switchable optoelectronic materials. 

PMID- 25779772
TI  - Highly uniform and vertically aligned SnO2 nanochannel arrays for photovoltaic
      applications.
AB  - Nanostructured electrodes with vertical alignment have been considered ideal
      structures for electron transport and interfacial contact with redox electrolytes
      in photovoltaic devices. Here, we report large-scale vertically aligned SnO2
      nanochannel arrays with uniform structures, without lateral cracks fabricated by
      a modified anodic oxidation process. In the modified process, ultrasonication is
      utilized to avoid formation of partial compact layers and lateral cracks in the
      SnO2 nanochannel arrays. Building on this breakthrough, we first demonstrate the
      photovoltaic application of these vertically aligned SnO2 nanochannel arrays.
      These vertically aligned arrays were directly and successfully applied in quasi
      solid state dye-sensitized solar cells (DSSCs) as photoanodes, yielding
      reasonable conversion efficiency under back-side illumination. In addition, a
      significantly short process time (330 s) for achieving the optimal thickness (7.0
      MUm) and direct utilization of the anodized electrodes enable a simple, rapid and
      low-cost fabrication process. Furthermore, a TiO2 shell layer was coated on the
      SnO2 nanochannel arrays by the atomic layer deposition (ALD) process for
      enhancement of dye-loading and prolonging the electron lifetime in the DSSC.
      Owing to the presence of the ALD TiO2 layer, the short-circuit photocurrent
      density (Jsc) and conversion efficiency were increased by 20% and 19%,
      respectively, compared to those of the DSSC without the ALD TiO2 layer. This
      study provides valuable insight into the development of efficient SnO2-based
      photoanodes for photovoltaic application by a simple and rapid fabrication
      process. 

PMID- 25779773
TI  - "Learning how to deal with feelings differently": Psychotropic medications as
      vehicles of socialization in adolescence.
AB  - Drawing from ethnographic research among clinicians working with adolescents at a
      hospital psychiatric emergency department and outpatient clinic, and with
      interviews with adolescent psychiatric patients and their parents, we examine how
      psychiatric medicines function as socializing agents. Although psychiatric
      medications are thought to exert their main effects through direct biological
      action on neural circuitry, in fact, their use mobilizes specific kinds of moral
      discourse and social positioning that may have profound effects on sense of self,
      personhood, and psychological development. Specifically, our data reveal how
      clinical discourse around medications aims to enlist adolescents in becoming
      responsible, emotionally intelligent selves through learning to manage their
      medications. Among doctors, adolescents and their families, talk about
      psychiatric medications intertwines narratives of 'growing up' and 'getting
      well'. Our analysis of case studies from the clinic thus demonstrates that while
      psychiatric medications are explicitly designed to influence behavior by acting
      directly on the brain, they also act to structure adolescents' selves and social
      worlds through indirect, rather than direct causal pathways to the brain. 

PMID- 25779774
TI  - Diet and obesity in Los Angeles County 2007-2012: Is there a measurable effect of
      the 2008 "Fast-Food Ban"?
AB  - We evaluate the impact of the "Los Angeles Fast-Food Ban", a zoning regulation
      that has restricted opening/remodeling of standalone fast-food restaurants in
      South Los Angeles since 2008. Food retail permits issued after the ban are more
      often for small food/convenience stores and less often for larger restaurants not
      part of a chain in South Los Angeles compared to other areas; there are no
      significant differences in the share of new fast-food chain outlets, other chain
      restaurants, or large food markets. About 10% of food outlets are new since the
      regulation, but there is little evidence that the composition has changed
      differentially across areas. Data from the California Health Interview Survey
      show that fast-food consumption and overweight/obesity rates have increased from
      2007 to 2011/2012 in all areas. The increase in the combined prevalence of
      overweight and obesity since the ban has been significantly larger in South Los
      Angeles than elsewhere. A positive development has been a drop in soft drink
      consumption since 2007, but that drop is of similar magnitude in all areas. 

PMID- 25779775
TI  - Assessment of superior semicircular canal thickness with advancing age.
AB  - OBJECTIVE: To determine whether superior semicircular canal dehiscence (SSCD) is
      more prevalent with advancing age. STUDY DESIGN: Retrospective observational
      study. METHODS: High-resolution computed-tomographic temporal bone scans were
      identified for patients of all ages and analyzed by two independent assessors.
      Multiplanar reconstruction was applied, and the thinnest area of temporal bone
      overlying each superior semicircular canal (SSC) was measured. RESULTS: A sample
      of 121 patients was analyzed that contained an almost identical number of male
      and female patients. In total, 242 temporal bone images were reviewed. Patients'
      ages ranged between 6 and 86 years. Age was shown to have a significant linear
      relationship (P < 0.001) such that for every unit increase in age the predicted
      thickness was reduced by 0.0047 mm. CONCLUSIONS: The thickness of the SSC
      decreases with advancing age. LEVEL OF EVIDENCE: 4.

PMID- 25779776
TI  - Reply: To PMID 25156222.

PMID- 25779777
TI  - Radiation-induced carotid stenosis: perioperative and late complications of
      surgical and endovascular treatment.
AB  - BACKGROUND: The surgical treatment of radio-induced carotid stenosis (RICS) is
      challenging and burdened with high risk of complications. Carotid stenting (CAS)
      may be a valid alternative, but better approach is still not defined. Two
      approaches have been assessed in this an observational monocentric study,
      focusing on perioperative and follow-up complications. METHODS: From 2005 to
      2013, data on patients treated for extracranial carotid stenosis with previous
      radiotherapy (RT) for head or neck tumor were prospectively collected according
      to the procedure performed (open repair [OR], endovascular stenting [CAS]).
      Patient demographics, clinical risk factors, organ of cancer origin, elapsed time
      from RT, duplex ultrasound (DUS) and clinical presentation of carotid stenosis
      were preoperatively gathered. Primary outcomes were technical success, 30-day
      mortality, transient ischemic attack (TIA)/stroke and myocardial infarction (MI).
      In OR group, laterocervical hematoma and cranial nerve injury were evaluated and,
      in CAS group, arterial access site complications were considered as well.
      Secondary outcomes were the mortality, TIA/stroke, restenosis and reintervention
      during follow-up. RESULTS: Fifteen RICS were treated in 12 patients (M/F=9/3;
      median age: 71 years, range: 51-80). OR was performed to treat 8 RICS in 5
      patients (M/F=3/2; median age: 65, range: 50-76) and CAS to treat 7 RICS in 7
      patients (M/F=6/1; median age: 75, range 59-80). In OR group, all patients were
      asymptomatic and all plaques were hypoechogenic at DUS with histological features
      of vulnerable plaque. Technical success was 100%. Thirty-day mortality was 12.5%
      (1 death for upper airways complication in patient with previous neck surgery).
      TIA/stroke and MI rate were 0% and cranial nerve injury 12.5%. In CAS group,
      carotid stenosis was symptomatic in 2(28.6%) cases, all plaques resulted
      hypoechogenic at DUS. Technical success was 100%. Thirty-day mortality was 0%.
      TIA occurred in 4 (57.1%) patients. No stroke, MI or access site hematoma
      occurred in this group. Mean follow-up was 35.5+/-18.2 months. At 12 and 36
      month, freedom from neurological events, restenosis and reintervention was 100%.
      At 1 and 3 years, survival was 91.7% and 81.5%, respectively. No patient died for
      carotid-related or cardiovascular causes. CONCLUSIONS: According with the plaque
      morphology and the high rate of cerebrovascular complications of CAS, OR should
      be suggested as the first choice for treatment of RICS in the majority of cases.
      In patients with previous neck surgery, assessment of airways is necessary before
      OR to avoid respiratory complications.

PMID- 25779778
TI  - In vivo real-time imaging of airway dynamics during bronchial challenge test.
AB  - BACKGROUND AND OBJECTIVE: Asthmatic patients exhibit airway hyper-responsiveness,
      which induces bronchoconstriction and results in a ventilation defect. The
      bronchial challenge test using methacholine is a useful way to measure airway
      hyper-responsiveness with airway constriction. Anatomical optical coherence
      tomography has been used to image airway hyper-responsiveness of medium sized
      bronchus with the aid of an endoscopic probe. Recently, a thoracic window was
      reported that allows direct visualization of terminal airway such as alveolus. A
      multi-scale integrated airway dynamics was assessed in this study. We imaged in
      vivo changes in the right intermedius bronchus and alveolar structure during the
      bronchial challenge test using two optical coherence tomography systems and
      correlated the changes with airway resistance. MATERIALS AND METHODS: Rabbits
      intubated with a non-cuffed endotracheal tube on a ventilator sequentially
      inhaled normal saline and methacholine (2 or 5 MUg/ml). The airway resistance was
      measured by mechanical ventilation and airway structures were monitored by a
      commercial endoscopic optical coherence tomography system (1,310 nm) and a house
      made table-top spectral-domain optical coherence tomography system (850 nm).
      RESULTS: We demonstrated an early decrease in the size of the right intermedius
      bronchus and alveoli in accordance with increased airway resistance after
      methacholine inhalation. OCT image after inhalation of 2 MUg/ml methacholine
      showed some segmental narrowing of the right intermedius bronchus and the image
      after inhalation of 5 MUg/ml methacholine showed even greater segmental
      narrowing. The cross-sectional areas were 7.2 +/- 3.3 mm2 (normal saline), 3.7 +/
      2.1 mm2 (2 MUg/ml methacholine), and 2.4 +/- 1.1 mm2 (5 MUg/ml methacholine),
      respectively (P = 0.04). Most of the alveolar space was collapsed under elevated
      airway resistance with methacholine inhalation. The averaged areas per alveolus
      at the end of inspiration were 0.0244 +/-0.0142 mm2 (normal saline), 0.0046 +/
      0.0026 mm2 (2 MUg/ml methacholine), and 0.0048 +/-0.0028 mm2 (5 MUg/ml
      methacholine), respectively (P = 0.03). Methacholine induced a dose-dependent
      increase in airway resistance (1.1 +/- 0.3 cm H2O sec/ml for 2 MUg/ml
      methacholine, 1.5 +/- 0.5 cm H2O sec/ml for 5 MUg/ml methacholine) (P = 0.03).
      These results were obtained from normal rabbits during the bronchial challenge
      test with a non-cuffed endotracheal tube on a ventilator. With this setup
      increased airway resistance possibly resulted in larger leakage around the
      endotracheal tube, decreased inhaled volumes, and, in turn, alveolar collapse.
      CONCLUSION: We performed a feasibility study of in vivo visualization of real
      time airway dynamics. To our best knowledge, this is the first report of real
      time integrated airway dynamics including the right intermedius bronchus and
      alveoli during a bronchial challenge test. OCT showed bronchial constriction and
      alveolar collapse with a higher methacholine dose. OCT images correlated with the
      measured airway resistance. Therefore, OCT could be a potential diagnostic device
      for airway hyper-responsiveness and airway remodeling.

PMID- 25779822
TI  - Dynamically self-assembled silver nanoparticles as a thermally tunable
      metamaterial.
AB  - The availability of metamaterials with properties that can be actively tuned is
      crucial for the future development of various metamaterial-based technologies.
      Here we show that by using silver nanoparticles equipped with a thermally
      responsive organic coating a metamaterial is obtained with reversibly switchable
      properties. The material investigated exhibits dynamic self-assembly resulting
      from temperature-dependent changes of organic coating shape, which translates to
      a switchable spatial distribution of the silver nanoparticles. This in turn
      strongly influences the optical properties of the entire material. The measured
      optical characteristics of the material are in excellent agreement with
      theoretical calculations, which allow us to use the latter to predict a
      dynamically tunable epsilon-near-zero behaviour of the metamaterial. The
      suggested methodology opens new routes for tunable metamaterials that operate in
      the visible region and will enable various applications for soft-matter-based
      optical devices. 

PMID- 25779823
TI  - Tangential flow ultrafiltration for detection of white spot syndrome virus (WSSV)
      in shrimp pond water.
AB  - Water represents the most important component in the white spot syndrome virus
      (WSSV) transmission pathway in aquaculture, yet there is very little information.
      Detection of viruses in water is a challenge, since their counts will often be
      too low to be detected by available methods such as polymerase chain reaction
      (PCR). In order to overcome this difficulty, viruses in water have to be
      concentrated from large volumes of water prior to detection. In this study, a
      total of 19 water samples from aquaculture ecosystem comprising 3 creeks, 10
      shrimp culture ponds, 3 shrimp broodstock tanks and 2 larval rearing tanks of
      shrimp hatcheries and a sample from a hatchery effluent treatment tank were
      subjected to concentration of viruses by ultrafiltration (UF) using tangential
      flow filtration (TFF). Twenty to 100l of water from these sources was
      concentrated to a final volume of 100mL (200-1000 fold). The efficiency of
      recovery of WSSV by TFF ranged from 7.5 to 89.61%. WSSV could be successfully
      detected by PCR in the viral concentrates obtained from water samples of three
      shrimp culture ponds, one each of the shrimp broodstock tank, larval rearing
      tank, and the shrimp hatchery effluent treatment tank with WSSV copy numbers
      ranging from 6 to 157mL(-1) by quantitative real time PCR. The ultrafiltration
      virus concentration technique enables efficient detection of shrimp viral
      pathogens in water from aquaculture facilities. It could be used as an important
      tool to understand the efficacy of biosecurity protocols adopted in the
      aquaculture facility and to carry out epidemiological investigations of aquatic
      viral pathogens. 

PMID- 25779824
TI  - A TaqMan qPCR for quantitation of Ungulate protoparvovirus 1 validated in several
      matrices.
AB  - Ungulate protoparvovirus 1 (UPV1) is one of the major causes of reproductive
      disorders in swine. Recently, the rapid viral evolution of UPV1 and its viral
      persistence in several tissues has been described. Based upon this, a real-time
      qPCR method using upgraded primers targeting VP1 and applying the TaqMan
      technology was developed in this study for UPV1, and it was validated in feces,
      serum and tissue. Within the results, the limit of detection of the qPCR was
      100copies of the viral genome per reaction of serum and feces and 1000copies of
      the viral genome per reaction of the grinded tissue (pre-inoculated matrices with
      diluted serially viruses). No cross reactivity was observed with other viruses
      associated with reproductive disorders. The assay was specific and reproducible,
      presenting low intra- and inter-assay variation (0.93% and 1.06%, respectively).
      In 50 clinical samples, the method was found to be more sensitive than
      immunofluorescence and a SYBR Green PCR. In conclusion, this qPCR represents an
      upgraded and useful tool to quantify UPV1 in different sample matrices for
      diagnostic and research purposes. 

PMID- 25779825
TI  - Cardioprotection by curcumin post-treatment in rats with established chronic
      kidney disease.
AB  - PURPOSE: The pathogenic mechanisms leading to cardiovascular disorders in
      patients with chronic kidney disease have not been clearly established, although
      increased oxidative stress has been pointed out as a potential cause. Therefore,
      as cardiovascular events are still the first cause of death in patients with
      chronic kidney disease and traditional drugs or therapies rarely have effects on
      cardiac complications, we sought to determine the effect of curcumin in treating
      cardiac dysfunction in rats with established chronic renal disease. METHODS AND
      RESULTS: Treatment consisted in daily administration of curcumin (120 mg/kg/day)
      dissolved in 0.05% carboxymethylcellulose via oral gavages during 30 days,
      beginning from day 30 after 5/6 nephrectomy (5/6Nx). Cardiac function, markers of
      oxidative stress, activation of PI3K/Akt/GSK3beta and MEK1/2-ERK1/2 pathway,
      metalloproteinase-II (MMP-2) content, overall gelatinolytic activity, ROS
      production and mitochondrial integrity were evaluated after 1-month treatment.
      Curcumin restored systolic blood pressure, diminished interventricular and rear
      wall thickening, decreased left ventricle dimension at end-systole (LVSd) and
      restored ejection fraction in nephrectomized rats. Also, it diminished
      metalloproteinase-II levels and overall gelatinase activity, decreased oxidative
      stress and inhibited the mitochondrial permeability transition pore opening.
      CONCLUSION: Our findings suggest that curcumin might have therapeutic potential
      in treatment of heart disease in patients with established CKD by attenuating
      oxidative stress-related events as cardiac remodeling, mitochondrial dysfunction
      and cell death.

PMID- 25779826
TI  - Optimal insertion lengths of right and left internal jugular central venous
      catheters in children.
AB  - BACKGROUND: Knowledge of the optimal lengths for central venous catheterization
      prior to the procedure may lessen the need for repositioning and prevent vascular
      complications. OBJECTIVE: To establish the optimal lengths for non-tunneled
      central venous catheter insertion through the right and left internal jugular
      veins. MATERIALS AND METHODS: We included 92 children who received US-guided
      central venous catheterization via right or left internal jugular veins in
      intensive care units. The calculated distance between the skin and carina was
      considered the optimal length for right and left internal jugular venous
      catheterization. Univariate and multivariate linear regression analyses was used
      to identify predictors. RESULTS: Age, height and weight showed significant
      correlations with optimal insertion lengths for right and left internal jugular
      vein approaches on univariate analysis, while height was the only significant
      independent predictor of optimal insertion length. CONCLUSION: The optimal
      insertion lengths (cm) suggested by our data are, for the right internal jugular
      vein 0.034 * height (cm) + 3.173, and for the left 0.072 * height (cm) + 2.113.

PMID- 25779827
TI  - Periventricular hyperintensity in children with hydrocephalus.
AB  - BACKGROUND: Magnetic resonance images of children with hydrocephalus often
      include a rim of hyperintensity in the periventricular white matter (halo).
      OBJECTIVE: The purpose of this study was to decide between the hypothesis that
      the halo is caused by cerebrospinal fluid (CSF) flow during the cardiac cycle,
      and the alternate hypothesis that the halo is caused by anatomical changes
      (stretching and compression of white matter). MATERIALS AND METHODS: Participants
      were selected from a multicenter imaging study of pediatric hydrocephalus. We
      compared 19 children with hydrocephalus to a group of 52 controls. We quantified
      ventricle enlargement using the frontal-occipital horn ratio. We conducted
      qualitative and quantitative analysis of diffusion tensor imaging in the corpus
      callosum and posterior limb of the internal capsule. Parameters included the
      fractional anisotropy (FA), mean diffusivity, axial diffusivity and radial
      diffusivity. RESULTS: The halo was seen in 16 of the 19 children with
      hydrocephalus but not in the controls. The corpus callosum of the hydrocephalus
      group demonstrated FA values that were significantly decreased from those in the
      control group (P = 4 . 10(-6)), and highly significant increases were seen in the
      mean diffusivity and radial diffusivity in the hydrocephalus group. In the
      posterior limb of the internal capsule the FA values of the hydrocephalus group
      were higher than those for the control group (P = 0.002), and higher values in
      the hydrocephalus group were also noted in the axial diffusivity. We noted
      correlations between the diffusion parameters and the frontal-occipital horn
      ratio. CONCLUSION: Our results strongly support the hypothesis that the halo
      finding in hydrocephalus is caused by structural changes rather than pulsatile
      CSF flow.

PMID- 25779828
TI  - High-resolution coronary MR angiography for evaluation of patients with anomalous
      coronary arteries: visualization of the intramural segment.
AB  - BACKGROUND: Anomalous origin of the coronary artery from the contralateral
      coronary sinus is a rare coronary anomaly associated with sudden death. The inter
      arterial course is most closely associated with sudden death, but it has been
      suggested that the presence of an intramural segment of a right anomalous
      coronary is associated with more symptoms and therefore may be an important
      criterion for intervention in these patients. OBJECTIVE: To demonstrate that MR
      angiography can accurately determine the presence or absence of an intramural
      segment in an anomalous coronary artery. MATERIALS AND METHODS: All studies of
      children who underwent MR angiography for the evaluation of an anomalous coronary
      artery were retrospectively reviewed by two pediatric radiologists in consensus.
      Criteria for an intramural anomalous coronary artery were the presence of a small
      or slit-like ostium and the relative smaller size of the proximal intramural
      portion of the coronary artery in relation to the more distal epicardial coronary
      artery. The anomalous coronary artery was classified as not intramural if these
      two findings were absent. These findings were correlated with operative reports
      confirming the presence or absence of an intramural segment. RESULTS: Twelve
      patients (86%) met MR angiography criteria for the presence of an intramural
      course. Only 2 patients (14%) met MR angiography criteria for a non-intramural
      course. When correlating with intraoperative findings, MR angiography was
      successful in distinguishing between intramural and non-intramural anomalous
      coronary arteries in all cases (P = 0.01). CONCLUSION: MR angiography may be able
      to reliably identify the intramural segment of an anomalous coronary artery in
      older children using the imaging criteria of a small or slit-like ostium and
      relative decrease in size of the proximal portion of the anomalous coronary
      artery compared to the distal portion of the anomalous coronary artery.
      Determining the presence of the intramural segment may help with surgical
      planning and may be an important criterion for the determination of intervention
      in patients with inter-arterial anomalous right coronary arteries.

PMID- 25779829
TI  - Tracheal quadrifurcation associated with congenital heart disease.
AB  - Tracheal anomalies are known in association with congenital cardiac defects. Some
      of the well-described anomalies include accessory (displaced) tracheal bronchus
      with variants, tracheal trifurcation and accessory cardiac bronchus. Here we
      describe a case of tracheal quadrifurcation associated with complex congenital
      heart disease. Illustration of complex airway anatomy was simplified by the use
      of multidetector CT using a variety of image display options. Awareness of this
      complex anomaly will expand our knowledge of tracheal anomalies and equip the
      anesthesia and surgical team for better airway management. 

PMID- 25779830
TI  - Craniovertebral junction stenosis in Lenz-Majewski syndrome.
AB  - We report a girl with Lenz-Majewski syndrome associated with craniovertebral
      junction stenosis that led to communicating hydrocephalus and cervical
      myelopathy. The life-threatening complication was related to progressive
      craniovertebral hyperostosis that rapidly exacerbated during early childhood.
      Despite initial success of surgical intervention at 2 years of age, she developed
      apneic spells and died suddenly at age 5 years. Close monitoring for
      craniovertebral junction stenosis is essential to reduce morbidity and mortality
      in children with Lenz-Majewski syndrome.

PMID- 25779846
TI  - Preparation, characterization, and silanization of 3D microporous PDMS structure
      with properly sized pores for endothelial cell culture.
AB  - Nowadays, application of porous polydimethylsiloxane (PDMS) structure in
      biomedical is becoming widespread, and many methods have been established to
      create such structure. Although the pores created through these methods are
      mostly developed on the outer surface of PDMS membrane, this study offers a
      simple and cost-efficient technique for creating three-dimensional (3D)
      microporous PDMS structure with appropriate pore size for endothelial cell
      culture. In this study, combination of gas foaming and particulate leaching
      methods, with NaHCO3 as effervescent salt and NaCl as progen are used to form a
      3D PDMS sponge. The in situ chemical reaction between NaHCO3 and HCl resulted in
      the formation of small pores and channels. Moreover, soaking the samples in HCl
      solution temporarily improved the hydrophilicity of PDMS, which then facilitated
      the penetration of water for further leaching of NaCl. The surface chemical
      modification process was performed by (3-aminopropyl)triethoxysilane to culture
      endothelial cells on porous PDMS matrix. The results are an indication of
      positive response of endothelial cells to the fabricated PDMS sponge. Because of
      simplicity and practicality of this method for preparing PDMS sponge with
      appropriate pore size and biological properties, the fabricated matrix can
      perfectly be applied to future studies in blood-contacting devices. 

PMID- 25779847
TI  - Angiotensin-(1-7) stimulates cholesterol efflux from angiotensin II-treated
      cholesterol-loaded THP-1 macrophages through the suppression of p38 and c-Jun N
      terminal kinase signaling.
AB  - Angiotensin II (Ang II) and Ang-(1-7) are key effector peptides of the renin
      angiotensin system. The present study aimed to investigate the effects of Ang-(1
      7) on Ang II-stimulated cholesterol efflux and the associated molecular
      mechanisms. Differentiated THP-1 macrophages were treated with Ang II (1 uM)
      and/or Ang-(1-7) (10 and 100 nM) for 24 h and the cholesterol efflux and gene
      expression levels were assessed. Pharmacological inhibition of peroxisome
      proliferator-activated receptor (PPAR)gamma and mitogen-activated protein kinases
      (MAPKs) were performed to identify the signaling pathways involved. The results
      demonstrated that Ang II significantly inhibited the cholesterol efflux from
      cholesterol-loaded THP-1 macrophages. Treatment with Ang-(1-7) led to a dose
      dependent restoration of cholesterol efflux in the Ang II-treated cells. The co
      treatment with Ang-(1-7) and Ang II significantly increased the expression levels
      of adenosine triphosphate (ATP)-binding cassette (ABC)A1 and ABCG1 compared with
      treatment with Ang II alone. This was coupled with increased expression levels of
      PPARgamma and liver X receptor (LXR)alpha. The pharmacological inhibition of
      PPARgamma significantly (P<0.05) eliminated the Ang-(1-7)-mediated induction of
      ABCA1 and ABCG1 mRNA expression. Treatment with Ang-(1-7) caused the inactivation
      of c-Jun N-terminal kinases (JNK) and p38 MAPK signaling in the Ang II-treated
      THP-1 macrophages. In addition, the inhibition of JNK or p38 MAPK signaling using
      specific pharmacological inhibitors mimicked the Ang-(1-7)-induced expression of
      PPARgamma and LXRalpha. In conclusion, the data demonstrated that treatment with
      Ang-(1-7) promoted cholesterol efflux in Ang II-treated THP-1 macrophages, partly
      through inactivation of p38 and JNK signaling and by inducing the expression of
      PPARgamma and LXRalpha. Ang (1-7) may, therefore, have therapeutic benefits for
      the treatment of atherosclerosis.

PMID- 25779848
TI  - Therapeutic targeting of the thrombospondin-1 receptor CD47 to treat liver
      cancer.
AB  - CD47 is a signaling receptor for the matricellular protein thrombospondin-1 and a
      counter-receptor for signal regulatory protein-alpha (SIRPalpha) on macrophages.
      Following its initial discovery in 1992 as a cell surface protein that is over
      expressed by ovarian carcinoma, elevated CD47 expression has emerged as a
      negative prognostic factor for a variety of cancers. CD47 is also a potential
      therapeutic target based on the ability of CD47 blockade to cause regression of
      tumors in mice, and a humanized CD47 antibody has recently entered phase I
      clinical trials. CD47 blockade may control tumor growth by inhibiting
      thrombospondin-1 signaling or by preventing inhibitory SIRPalpha signaling in
      tumor-associated macrophages. A recent publication by Lee et al. (Hepatology
      60:179-191, 2014) provides evidence that blocking CD47 signaling specifically
      depletes tumor-initiating stem cells in hepatocellular carcinoma and implicates
      cathepsin-S/protease-activated receptor-2 signaling in mediating this therapeutic
      response. 

PMID- 25779849
TI  - Suplatast tosilate for treating cutaneous mastocytosis.
AB  - Pediatric cutaneous mastocytosis is a rare disease caused by mast cell
      hyperplasia. We report the case of an infant diagnosed as cutaneous mastocytosis
      and seasonal allergies. The wheals, flushing, and pruritus of the mastocytosis
      were unresponsive to combination therapy with an antihistamine, a mast cell
      stabilizer (sodium cromoglycate), and a leukotriene antagonist. Addition of
      suplatast tosilate as a treatment for the seasonal allergy also dramatically
      improved his cutaneous symptoms and signs. Further trials of suplatast tosilate
      in selected cases of cutaneous mastocytosis are warranted. 

PMID- 25779850
TI  - The activity of class I, II, III and IV alcohol dehydrogenase isoenzymes and
      aldehyde dehydrogenase in renal cell carcinoma.
AB  - OBJECTIVES: Ethanol has been considered as a lifestyle risk factor for cancer in
      humans. While some studies have indicated that alcohol intake has a preventive
      effect for renal cell cancer, others have not. The metabolism of alcohol in
      cancer cells may be in many ways different than in healthy tissue and its
      disturbances could be associated with carcinogenesis. The aim of this study was
      to compare the metabolism of renal cell cancer cells and normal renal cells by
      measurement of ADH isoenzymes and ALDH activities in these tissues. MATERIAL AND
      METHODS: The study material consisted of 43 cancerous renal tissues (14 patients
      in stage II, 19 in stage III and 10 in stage IV). Class III and IV ADH and total
      ADH activities were measured by the photometric method and class I and II ADH and
      ALDH activities by the fluorometric method with class-specific fluorogenic
      substrates. RESULTS: The activity of the class I ADH isoenzyme and the total ADH
      was significantly higher in every stage of renal cell cancer as compared to
      healthy tissues. Analysis of ALDH activity did not show statistically significant
      differences between cancer and healthy cells. CONCLUSION: The increased activity
      of total ADH in renal cell cancer, especially the class I isoenzyme and normal
      activity of ALDH, may be the factor intensifying carcinogenesis because of
      increasing the ability to highly carcinogenic acetaldehyde formation and causing
      disorders in metabolism of many biologically important substances.

PMID- 25779851
TI  - Identifying relationships between symptom clusters and quality of life in adults
      with chronic mixed venous and arterial leg ulcers.
AB  - The objective of this study was to identify symptom clusters and their effect on
      quality of life (QOL) of adults with chronic leg ulcers of mixed venous and
      arterial aetiology. A secondary analysis of data from four existing prospective
      longitudinal studies conducted by a wound healing research group in Australia was
      undertaken. A total of 110 patients who met the inclusion criteria were selected
      for this study. Exploratory factor analysis (EFA) was used to identify symptom
      clusters and correlational analyses to examine relationships between the
      identified symptom clusters and QOL. The EFA identified two distinct symptom
      clusters: a 'systemic symptom cluster' consisting of pain, fatigue and depressive
      symptoms; and a 'localised-leg symptom cluster' including pain, fatigue, oedema,
      lower limb inflammation and exudate. Physical QOL correlated significantly with
      the systemic symptom cluster (r = -0.055, P < 0.0001) and the localised-leg
      symptom cluster (r = -0.054, P < 0.0001), whereas mental QOL was associated only
      with the systemic symptom cluster (r = -0.038, P = 0.01). The results suggest
      that appropriate intervention strategies targeting specific symptom clusters
      should be developed. Targeting patients with symptom clusters is particularly
      important because they are at high risk and the most vulnerable for reduced QOL. 

PMID- 25779852
TI  - Microcatheter Shaping for Intracranial Aneurysm Coiling Using the 3-Dimensional
      Printing Rapid Prototyping Technology: Preliminary Result in the First 10
      Consecutive Cases.
AB  - OBJECTIVE: An optimal microcatheter is necessary for successful coiling of an
      intracranial aneurysm. The optimal shape may be predetermined before the
      endovascular surgery via the use of a 3-dimensional (3D) printing rapid
      prototyping technology. We report a preliminary series of intracranial aneurysms
      treated with a microcatheter shape determined by the patient's anatomy and
      configuration of the aneurysm, which was fabricated with a 3D printer aneurysm
      model. METHODS: A solid aneurysm model was fabricated with a 3D printer based on
      the data acquired from the 3D rotational angiogram. A hollow aneurysm model with
      an identical vessel and aneurysm lumen to the actual anatomy was constructed with
      use of the solid model as a mold. With use of the solid model, a microcatheter
      shaping mandrel was formed to identically line the 3D curvature of the parent
      vessel and the long axis of the aneurysm. With use of the mandrel, a test
      microcatheter was shaped and validated for the accuracy with the hollow model.
      All the planning processes were undertaken at least 1 day before treatment. The
      preshaped mandrel was then applied in the endovascular procedure. Ten consecutive
      intracranial aneurysms were coiled with the pre-planned shape of the
      microcatheter and evaluated for the clinical and anatomical outcomes and
      microcatheter accuracy and stability. RESULTS: All of pre-planned microcatheters
      matched the vessel and aneurysm anatomy. Seven required no microguidewire
      assistance in catheterizing the aneurysm whereas 3 required guiding of a
      microguidewire. All of the microcatheters accurately aligned the long axis of the
      aneurysm. The pre-planned microcatheter shapes demonstrated stability in all
      except in 1 large aneurysm case. CONCLUSION: When a 3D printing rapid type
      prototyping technology is used, a patient-specific and optimal microcatheter
      shape may be determined preoperatively.

PMID- 25779853
TI  - Biomechanical Analysis of a Novel Pedicle Screw Anchor Designed for the
      Osteoporotic Population.
AB  - OBJECTIVE: The biomechanical study was performed to investigate the effect of a
      novel pedicle screw anchor in increasing the pullout strength of pedicle screws.
      METHODS: Ten lumbar vertebral bodies with a weighted average T-score of -2.13
      were used. Pedicle screws of 4.5 mm diameter and 25 mm length were inserted in to
      one pedicle randomly and matched with an anchor in the corresponding pedicle.
      Fatigue testing was performed by applying an axial load of +/-200N to the screw
      tulip, along the axis of the rod, at a rate of 0.5 Hz for 1,000 cycles. After
      fatigue loading was completed, all screws underwent axial pullout testing at a
      rate of 0.1 mm/sec until failure. A paired two sample for means t-test was
      performed to determine a significant difference between the two groups (p <=
      0.05). RESULTS: Following fatigue testing, the axial displacement at the 1,000
      cycle point for the anchor and non-anchor group was 1.4 +/- 0.7mm and 2.9 +/-
      1.2mm, respectively. The anchor group had significantly lower axial displacement
      compared to the non-anchor group (p <= 0.01). The group with the anchor reached
      an average maximum load of 702 +/- 373N. The average yield load for the non
      anchor group was 421 +/- 293N. The anchor group yield load was significantly
      greater than the non-anchor group (p <= 0.01). CONCLUSIONS: A novel anchor for
      standard pedicle screws resulted in significantly less axial movement during
      fatigue and a greater failure force compared a screw with no anchor. The anchor
      may provide a stronger bone-to-screw interface, than a non-anchor screw, without
      the complications of cement augmentation.

PMID- 25779854
TI  - Prognostic Factors in Lobar World Health Organization Grade II Astrocytomas.
AB  - BACKGROUND: World Health Organization grade II astrocytomas (AII) are the
      commonest low-grade glioma subset, but their prognostic factors are subject to
      debate. This institutional study aimed to identify prognostic factors in lobar
      AII. METHODS: Retrospective review of newly diagnosed, lobar AII between 2006 and
      2012. Patient demographics, imaging, and treatment data were obtained. Isocitrate
      dehydrogenase-1 (IDH1) status was assessed via immunohistochemistry. Multivariate
      analysis was performed with Cox regression to identify prognostic factors for
      overall survival (OS) and progression-free survival (PFS). RESULTS: A total of 92
      adult patients were identified with a median age of 42 years (range 20-73 years)
      and median follow-up period of 45 months (range, 7-98 months). Seizures were the
      commonest mode of presentation (75%). IDH1 immunopositivity was seen in 46 of 83
      patients (55%). Radiology diagnosis agreed with histology in 76% of cases, and
      28% of tumors had documented evidence of some degree of contrast enhancement.
      Surgical management was either resection (51%) or biopsy (49%) and postoperative
      radiotherapy was used in patients with unfavorable prognostic features. The
      median OS and PFS were 85 months (range 2-98 months) and 36 months (95%
      confidence interval [95% CI] 27-45 months), respectively. Surgical resection (P <
      0.001; hazard ratio [HR] 5.072; 95% CI 2.050-12.550), absence of contrast
      enhancement (P = 0.006; HR 3.180; 95% CI 1.403-7.206), and IDH1 immunopositivity
      (P = 0.006; HR 3.310; 95% CI 1.416-7.738) were associated with improved OS. Good
      performance status (P = 0.005; HR 5.965; 95% CI 1.710-20.804) and absence of
      contrast enhancement (P < 0.001; HR 3.446; 95% CI 1.883-6.304) were associated
      with improved PFS. CONCLUSIONS: Patients with World Health Organization grade II
      astrocytomas have better overall survival if their tumor is nonenhancing,
      amenable to surgical resection, and exhibits the IDH1 mutation. These factors
      should be used to guide patient management and inform prognosis.

PMID- 25779855
TI  - Factors associated with oxyhemoglobin desaturation during rapid sequence
      intubation in a pediatric emergency department: findings from multivariable
      analyses of video review data.
AB  - OBJECTIVES: In a video-based study of rapid sequence intubation (RSI) in a
      pediatric emergency department (PED), 33% of children experienced oxyhemoglobin
      desaturation (SpO2 < 90%). To inform targeted improvement interventions, we
      planned multivariable analyses to identify patient and process variables
      (including time-based data around performance of key RSI process elements
      uniquely available from video review) associated with desaturation during
      pediatric RSI. METHODS: These were planned analyses of data collected during a
      retrospective, video-based study of RSI in a high-volume, academic PED. For
      variables with plausible associations with desaturation, multiple logistic
      regression and generalized estimating equations were used to identify those
      characteristics independently associated with desaturation at both the patient
      and the attempt levels. RESULTS: The authors analyzed video data from 114
      patients undergoing RSI over 12 months. Desaturation was more common in patients
      24 months of age and younger (59%) than in patients older than 24 months of age
      (10%). Variables associated with desaturation in patients 24 months of age and
      younger were duration of attempts (both individual and cumulative), the
      occurrence of esophageal intubation, a respiratory indication for intubation, and
      young age. The receiver operating characteristics curve for the model had an area
      under the curve of 0.80 (95% confidence interval [CI] = 0.67 to 0.92). Forty-six
      percent of desaturations occurred after 45 seconds of laryngoscopy, and 82% after
      30 seconds. The odds ratio for desaturation on individual attempts lasting longer
      than 30 seconds (vs. those 30 seconds or less) was 5.7 (95% CI = 2.26 to 14.36).
      CONCLUSIONS: For children 24 months of age or younger undergoing RSI in a PED,
      respiratory indication for intubation, esophageal intubation, and duration of
      laryngoscopy (both individual and cumulative) were associated with desaturation;
      the number of attempts was not. Interventions to limit attempt duration in the
      youngest children may improve the safety of RSI.

PMID- 25779856
TI  - Immunochemical Detection Methods for Gluten in Food Products: Where Do We Go from
      Here?
AB  - Accurate and reliable quantification methods for gluten in food are necessary to
      ensure proper product labeling and thus safeguard the gluten sensitive consumer
      against exposure. Immunochemical detection is the method of choice, as it is
      sensitive, rapid and relatively easy to use. Although a wide range of detection
      kits are commercially available, there are still many difficulties in gluten
      detection that have not yet been overcome. This review gives an overview of the
      currently commercially available immunochemical detection methods, and discusses
      the problems that still exist in gluten detection in food. The largest problems
      are encountered in the extraction of gluten from food matrices, the choice of
      epitopes targeted by the detection method, and the use of a standardized
      reference material. By comparing the available techniques with the unmet needs in
      gluten detection, the possible benefit of a new multiplex immunoassay is
      investigated. This detection method would allow for the detection and
      quantification of multiple harmful gluten peptides at once and would, therefore,
      be a logical advancement in gluten detection in food.

PMID- 25779857
TI  - Effect of a Realigning Brace on Tibiofemoral Contact Stress.
AB  - OBJECTIVE: To determine the degree to which focally elevated tibiofemoral joint
      contact stress is reduced by using a frontal plane realigning brace. METHODS:
      Fifteen volunteers (9 women) with unicompartmental tibiofemoral osteoarthritis
      underwent weight-bearing radiographic imaging at 15-20 degrees  and 5-10 degrees 
      of knee flexion with and without an UnloaderOne knee brace. Discrete element
      analysis was used to estimate compartment-specific contact stress distributions.
      Paired t-tests were used to assess the differences in mean contact stress and
      contact stress distributions, comparing the braced and unbraced conditions.
      RESULTS: The mean +/- SD age was 56.1 +/- 6.4 years and body mass index was 28.4
      +/- 4.5 kg/m(2). Twelve of 15 participants were fit with braces set to unload the
      medial compartment. For the 15-20 degrees  condition, the mean contact stress in
      the compartment of interest did not significantly change (0.08 +/- 0.35 MPa; P =
      0.410). Also at 5-10 degrees  flexion, the mean contact stress in the compartment
      of interest did not significantly change with use of the brace (0.24 +/- 0.45
      MPa; P = 0.175). CONCLUSION: This is the first study of the effects of a frontal
      plane realignment brace on in vivo articular contact stress in native human
      knees. Using the off-the-shelf brace tested, there were no changes in
      compartmental tibiofemoral contact stress distributions at either 15-20 degrees 
      or 5-10 degrees  of knee flexion, revealing no redistribution of contact stress
      away from the compartment of interest. These findings indicate that the brace
      that was studied was ineffective for redistributing tibiofemoral contact stress.
      Further research is necessary to determine whether double-upright or customized
      frontal plane braces are effective in redistributing compartmental articular
      contact stress.

PMID- 25779862
TI  - Non-invasive EEG evaluation in epilepsy diagnosis.
AB  - The EEG is an invaluable tool in the diagnosis of epilepsy which guides clinical
      management. It helps to determine if attacks are of epileptic origin, allows the
      estimation of the recurrence risk after a first seizure, aids in the diagnosis of
      the epilepsy syndrome and represents the gold standard in the presurgical
      evaluation of epilepsy. The EEG can also detect subclinical seizures as a cause
      of coma. In this review we discuss the sensitivity and specificity of the EEG,
      present the EEG findings and their significance in different epilepsy syndromes
      including focal and generalized epilepsies and describe the application of
      activation procedures. 

PMID- 25779863
TI  - Glial cell progenitors in the Drosophila embryo.
AB  - Development and general organization of the nervous system is comparable between
      insects and vertebrates. Our current knowledge on the formation of neurogenic
      anlagen and the generation of neural stem cells is deeply influenced by work done
      in invertebrate model organisms such as Drosophila and Caenorhabditis elegans. It
      is the aim of this review to summarize the most important steps in neurogenesis
      in the Drosophila embryo with a special emphasis on glial cell progenitors and
      the specification of glial cells. Induction of neurogenic regions during early
      embryogenesis and determination of neural stem cells are briefly described.
      Special attention is given to the formation of neural precursors called
      neuroblasts (NB) and their lineages. NBs divide in a stem cell mode to generate a
      cell clone of either neurons and/or glial cells. The latter require the
      activation of the transcription factor glial cells missing (gcm), thus providing
      a binary switch between neuronal and glial cell fates. Further aspects of glial
      cell specification and the resulting heterogeneity of the glial population in
      Drosophila are discussed.

PMID- 25779864
TI  - Are uric acid plasma levels different between unipolar depression with and
      without adult attention deficit hyperactivity disorder?
AB  - BACKGROUND: The aim of our study is to compare uric acid plasma levels in
      patients with unipolar depression between those with Attention deficit
      hyperactivity disorder (ADHD) comorbidity and those without. Our hypothesis is
      that uric acid plasma levels may be higher in unipolar depressive patients with
      adult ADHD than without ADHD. METHODS: Sixty four patients diagnosed with MDD
      were investigated, among which 28 patients had been diagnosed with ADHD according
      to DSM5. 28 patients were ADHD. 36 patients were diagnosed as not having ADHD.
      One of the criteria was including cases that had not started using medication for
      the current depressive episode. The control group (HC) consisted of 43 healthy
      staff members from our hospital who had no prior psychiatric admission or
      treatment history and matched with the patient group in terms of age and gender.
      Blood samples were obtained, and plasma uric acid levels were recorded in mg/dl
      after being rotated for 15min in a centrifuge with 3000 rotations and kept at -80
      degrees C. RESULTS: Uric acid plasma levels 5.1+/-1.6 in unipolar depression and
      ADHD group, 4.6+/-1.8 in unipolar depression group. Uric acid plasma levels were
      higher in the comorbid unipolar depression and ADHD group than in the unipolar
      depression and healthy control (HC) groups (F= 4.367, p= 0.037). There was no
      correlation between ADHD (predominantly inattentive type) and uric acid plasma
      levels (p>0.05). LIMITATIONS: The limitation of this study is the small number of
      sample and one of the criteria was including cases that had not started using
      medication for the current depressive episode. CONCLUSION: The identification of
      a different etiologic process of biological markers may lead to a better
      understanding of the physiological mechanisms involved in drive and impulsivity
      and may suggest different potential targets for therapeutic intervention.

PMID- 25779865
TI  - Evaluation of blood glucose fluctuation in Japanese patients with type 1 diabetes
      mellitus by self-monitoring of blood glucose and continuous glucose monitoring.
AB  - AIMS: Accurate assessment of blood glucose fluctuation is essential for managing
      blood glucose control while avoiding hypoglycemia in patients with diabetes
      mellitus. In this study, blood glucose was measured by continuous glucose
      monitoring (CGM) in patients with type 1 diabetes mellitus (T1DM) whom self
      monitoring of blood glucose (SMBG) was carried out three or more times per day,
      and evaluation was performed using blood glucose fluctuation parameters obtained
      by CGM and SMBG. METHODS: Twenty-nine insulin-depleted patients with T1DM were
      enrolled. Their blood glucose fluctuations were measured at the same time by SMBG
      and CGM, and the correlations were evaluated. RESULTS: Correlations were found
      between the following values obtained by SMBG and CGM: mean and standard
      deviation of blood glucose levels, average daily risk range, Morbus value and
      high-blood-glucose index. The hypoglycemia duration and the nocturnal
      hypoglycemia duration showed no correlation with any of the blood glucose
      fluctuation parameters obtained by SMBG. CONCLUSIONS: The findings suggest that
      routine SMBG and glycated hemoglobin (HbA1c) measurement are sufficient for
      evaluation of hyperglycemia in T1DM. On the other hand, blood glucose fluctuation
      parameters obtained by SMBG and HbA1c have been shown to have no correlations
      with either hypoglycemia duration or nocturnal hypoglycemia duration.

PMID- 25779866
TI  - The impact of severe hypoglycemia on renal impairment in type 2 diabetes.
AB  - AIMS: Hypoglycemia has been reported to be associated with the development of
      microvascular events. Therefore, it is important to assess the impact of severe
      hypoglycemia on renal dysfunction in type 2 diabetes. METHODS: We conducted a
      retrospective cohort study in a large tertiary care hospital from 2004 to 2013. A
      total of 101 patients with type 2 diabetes from the outpatient department with a
      history of severe hypoglycemia were studied. A random sample of 101 patients with
      type 2 diabetes without any hypoglycemia was selected by matching values of
      baseline blood creatinine, age, sex and diabetic duration. RESULTS: Baseline
      blood creatinine (1.42 +/- 0.75 mg/dL) significantly increased to 1.77 +/- 1.26
      and 1.93 +/- 1.54 mg/dL, and baseline eGFR (44.37 +/- 26.13 ml/min/1.73 m(2))
      decreased to 41.28 +/- 27.70 and 37.64 +/- 24.54 ml/min/1.73 m(2) at the onset of
      hypoglycemia and the follow-up visit in severe hypoglycemia group; while no
      significant changes were observed in the group without any hypoglycemia. Multiple
      linear regression analysis showed that severe hypoglycemia is an independent risk
      factor for increase in blood creatinine and decrease in eGFR in all patients with
      type 2 diabetes, and that baseline creatinine, longer diabetic duration and lower
      HbA1c are risk factors for the deterioration of renal impairment in the group
      with severe hypoglycemia. CONCLUSION: Our results showed that severe hypoglycemia
      is associated with deterioration of renal function in type 2 diabetes with
      chronic kidney disease and the patients with higher baseline creatinine and a
      longer diabetic duration could be more vulnerable to aggravation of renal
      function impairment.

PMID- 25779867
TI  - Erectile dysfunction cannot be used in primary screening of pre-diabetes.
AB  - We hypothesized that erectile dysfunction is associated with impaired fasting
      glucose and impaired glucose tolerance and could be used in primary screening of
      pre-diabetes. Although erectile dysfunction is known to be closely associated
      with diabetes, we demonstrate that it is not associated with pre-diabetes in 926
      apparently healthy men. 

PMID- 25779868
TI  - High spatial resolution proteomic comparison of the brain in humans and
      chimpanzees.
AB  - We performed high-throughput mass spectrometry at high spatial resolution from
      individual regions (anterior cingulate and primary motor, somatosensory, and
      visual cortices) and layers of the neocortex (layers III, IV, and V) and
      cerebellum (granule cell layer), as well as the caudate nucleus in humans and
      chimpanzees. A total of 39 mass spectrometry peaks were matched with probable
      protein identifications in both species, allowing for comparison in expression.
      We explored how the pattern of protein expression varies across regions and
      cortical layers to provide insights into the differences in molecular phenotype
      of these neural structures between species. The expression of proteins differed
      principally in a region- and layer-specific pattern, with more subtle differences
      between species. Specifically, human and chimpanzee brains were similar in their
      distribution of proteins related to the regulation of transcription and enzyme
      activity but differed in their expression of proteins supporting aerobic
      metabolism. Whereas most work assessing molecular expression differences in the
      brains of primates has been performed on gene transcripts, this dataset extends
      current understanding of the differential molecular expression that may underlie
      human cognitive specializations.

PMID- 25779869
TI  - Apparent lack of physical or functional interaction between CaV1.1 and its distal
      C terminus.
AB  - CaV1.1 acts as both the voltage sensor that triggers excitation-contraction
      coupling in skeletal muscle and as an L-type Ca(2+) channel. It has been proposed
      that, after its posttranslational cleavage, the distal C terminus of CaV1.1
      remains noncovalently associated with proximal CaV1.1, and that tethering of
      protein kinase A to the distal C terminus is required for depolarization-induced
      potentiation of L-type Ca(2+) current in skeletal muscle. Here, we report that
      association of the distal C terminus with proximal CaV1.1 cannot be detected by
      either immunoprecipitation of mouse skeletal muscle or by colocalized
      fluorescence after expression in adult skeletal muscle fibers of a CaV1.1
      construct labeled with yellow fluorescent protein (YFP) and cyan fluorescent
      protein on the N and C termini, respectively. We found that L-type Ca(2+) channel
      activity was similar after expression of constructs that either did (YFP
      CaV1.11860) or did not (YFP-CaV1.11666) contain coding sequence for the distal C
      terminal domain in dysgenic myotubes null for endogenous CaV1.1. Furthermore, in
      response to strong (up to 90 mV) or long-lasting prepulses (up to 200 ms), tail
      current amplitudes and decay times were equally increased in dysgenic myotubes
      expressing either YFP-CaV1.11860 or YFP-CaV1.11666, suggesting that the distal C
      terminal domain was not required for depolarization-induced potentiation. Thus,
      our experiments do not support the existence of either biochemical or functional
      interactions between proximal CaV1.1 and the distal C terminus. 

PMID- 25779870
TI  - Conditional knockout of TMEM16A/anoctamin1 abolishes the calcium-activated
      chloride current in mouse vomeronasal sensory neurons.
AB  - Pheromones are substances released from animals that, when detected by the
      vomeronasal organ of other individuals of the same species, affect their
      physiology and behavior. Pheromone binding to receptors on microvilli on the
      dendritic knobs of vomeronasal sensory neurons activates a second messenger
      cascade to produce an increase in intracellular Ca(2+) concentration. Here, we
      used whole-cell and inside-out patch-clamp analysis to provide a functional
      characterization of currents activated by Ca(2+) in isolated mouse vomeronasal
      sensory neurons in the absence of intracellular K(+). In whole-cell recordings,
      the average current in 1.5 uM Ca(2+) and symmetrical Cl(-) was -382 pA at -100
      mV. Ion substitution experiments and partial blockade by commonly used Cl(-)
      channel blockers indicated that Ca(2+) activates mainly anionic currents in these
      neurons. Recordings from inside-out patches from dendritic knobs of mouse
      vomeronasal sensory neurons confirmed the presence of Ca(2+)-activated Cl(-)
      channels in the knobs and/or microvilli. We compared the electrophysiological
      properties of the native currents with those mediated by heterologously expressed
      TMEM16A/anoctamin1 or TMEM16B/anoctamin2 Ca(2+)-activated Cl(-) channels, which
      are coexpressed in microvilli of mouse vomeronasal sensory neurons, and found a
      closer resemblance to those of TMEM16A. We used the Cre-loxP system to
      selectively knock out TMEM16A in cells expressing the olfactory marker protein,
      which is found in mature vomeronasal sensory neurons. Immunohistochemistry
      confirmed the specific ablation of TMEM16A in vomeronasal neurons. Ca(2+)
      activated currents were abolished in vomeronasal sensory neurons of TMEM16A
      conditional knockout mice, demonstrating that TMEM16A is an essential component
      of Ca(2+)-activated Cl(-) currents in mouse vomeronasal sensory neurons. 

PMID- 25779872
TI  - Sexual maturation pattern in the mirror of socioeconomic background.
AB  - The inequalities among the socioeconomic strata in the Hungarian society
      increased during the last decades. Since the socioeconomic conditions play a
      decisive part in shaping the growth and maturation of children, our purpose was
      to study the body structure and the growth and maturation pattern of children
      living in deprived regions in Hungary. Our former analysis revealed that the
      prevalence of non-normal nutritional status was significantly higher in children
      and adolescents living in the seriously deprived regions of Hungary than the
      national reference values. The main purpose of the present study was to compare
      the sexual maturation pattern of pubertal children living in the deprived regions
      by comparing the timing of pubertal maturation events to the national reference
      values. Sexual maturity status of 711 girls and 790 boys (aged 10 - 16 years)
      living in the deprived small regions of Hungary was compared to the national
      reference values (Hungarian National Growth Study II). Sexual maturity status was
      estimated by the stages of pubic hair, axillary hair, breast and external
      genitalia development, as well as by the menarcheal and spermarcheal status,
      respectively. The median ages of being in the pubertal stages of the sexual
      characteristics, menarcheal and spermarcheal age were estimated by probit
      analysis. By comparing it to the national reference values, the timing of
      pubertal development in boys and girls living in the seriously deprived regions
      showed a 1 - 3-month shift toward older ages. However, the length of sexual
      maturation: the interval between the median ages of the first and last pubertal
      stages of sexual characteristics was similar in the subjects living in the
      regions of Hungary as the Hungarian reference values. 

PMID- 25779871
TI  - Voltage-dependent gating and gating charge measurements in the Kv1.2 potassium
      channel.
AB  - Much has been learned about the voltage sensors of ion channels since the x-ray
      structure of the mammalian voltage-gated potassium channel Kv1.2 was published in
      2005. High resolution structural data of a Kv channel enabled the structural
      interpretation of numerous electrophysiological findings collected in various ion
      channels, most notably Shaker, and permitted the development of meticulous
      computational simulations of the activation mechanism. The fundamental premise
      for the structural interpretation of functional measurements from Shaker is that
      this channel and Kv1.2 have the same characteristics, such that correlation of
      data from both channels would be a trivial task. We tested these assumptions by
      measuring Kv1.2 voltage-dependent gating and charge per channel. We found that
      the Kv1.2 gating charge is near 10 elementary charges (eo), ~25% less than the
      well-established 13-14 eo in Shaker. Next, we neutralized positive residues in
      the Kv1.2 S4 transmembrane segment to investigate the cause of the reduction of
      the gating charge and found that, whereas replacing R1 with glutamine decreased
      voltage sensitivity to ~50% of the wild-type channel value, mutation of the
      subsequent arginines had a much smaller effect. These data are in marked contrast
      to the effects of charge neutralization in Shaker, where removal of the first
      four basic residues reduces the gating charge by roughly the same amount. In
      light of these differences, we propose that the voltage-sensing domains (VSDs) of
      Kv1.2 and Shaker might undergo the same physical movement, but the septum that
      separates the aqueous crevices in the VSD of Kv1.2 might be thicker than
      Shaker's, accounting for the smaller Kv1.2 gating charge. 

PMID- 25779873
TI  - Thermodynamic matchers for the construction of the cuckoo RNA family.
AB  - RNA family models describe classes of functionally related, non-coding RNAs based
      on sequence and structure conservation. The most important method for modeling
      RNA families is the use of covariance models, which are stochastic models that
      serve in the discovery of yet unknown, homologous RNAs. However, the performance
      of covariance models in finding remote homologs is poor for RNA families with
      high sequence conservation, while for families with high structure but low
      sequence conservation, these models are difficult to built in the first place. A
      complementary approach to RNA family modeling involves the use of thermodynamic
      matchers. Thermodynamic matchers are RNA folding programs, based on the
      established thermodynamic model, but tailored to a specific structural motif. As
      thermodynamic matchers focus on structure and folding energy, they unfold their
      potential in discovering homologs, when high structure conservation is paired
      with low sequence conservation. In contrast to covariance models, construction of
      thermodynamic matchers does not require an input alignment, but requires human
      design decisions and experimentation, and hence, model construction is more
      laborious. Here we report a case study on an RNA family that was constructed by
      means of thermodynamic matchers. It starts from a set of known but structurally
      different members of the same RNA family. The consensus secondary structure of
      this family consists of 2 to 4 adjacent hairpins. Each hairpin loop carries the
      same motif, CCUCCUCCC, while the stems show high variability in their nucleotide
      content. The present study describes (1) a novel approach for the integration of
      the structurally varying family into a single RNA family model by means of the
      thermodynamic matcher methodology, and (2) provides the results of homology
      searches that were conducted with this model in a wide spectrum of bacterial
      species. 

PMID- 25779874
TI  - [Intercalary reconstruction for diaphyseal bone defects with a modular
      replacement system: Clinical results].
AB  - OBJECTIVE: Reconstruction and long-term stabilization of segmental diaphyseal
      bone defects of the humerus, femur, and tibia. INDICATIONS: Segmental bone
      defects due to aggressive benign or primary malignant bone tumors, trauma,
      pathological fractures, osteomyelitis, or failed osteosynthesis.
      CONTRAINDICATIONS: Acute or chronic local infections, large metadiaphyseal bone
      defects preventing adequate anchorage of the prosthesis, very short life
      expectancy (<3 months). SURGICAL TECHNIQUE: Exposure and resection of the bony
      defect according to the preoperative planning. Reaming of the intramedullary
      canals proximally and distally followed by implantation of the stems (cemented or
      noncemented). Reducing sleeves can be used to bridge the difference in diameter
      between the nail and the spacer. Mounting of the spacer half shell with the
      threaded holes from underneath after adjusting for alignment and rotation.
      Assembling of the other half shell by guided pins to ensure proper alignment.
      Tightening of the clamping screws using a torque screwdriver. Connection of two
      spacers is possible. POSTOPERATIVE MANAGEMENT: Active physiotherapy and full
      weight bearing; antibiotic prophylaxis. RESULTS: The results of 14 consecutive
      patients treated with 15 modular intercalary endoprostheses (OsteobridgeTM,
      Merete, Berlin, Germany) between January 2007 and January 2012 with a mean follow
      up of 24 +/- 12 months (range 12-51 months) were evaluated retrospectively. One
      patient had a primary malignant bone tumor, while all the other patients
      underwent resection for metastatic disease. The mean age at surgery was 65.9 +/-
      15.7 years (range 25-83 years). The mean diaphyseal reconstruction length was 110
      +/- 50 mm (range 50-190 mm). Three patients (20%) required revision of the distal
      stem due to aseptic loosening. Evaluation of the functional outcome using the
      MSTS score by Enneking revealed 3 very good (22%), 7 good (50%), 4 fair (28%),
      and no poor results.

PMID- 25779875
TI  - Does the Aphid Alarm Pheromone (E)-beta-farnesene Act as a Kairomone under Field
      Conditions?
AB  - Insect natural enemies use several environmental cues for host/prey finding, and
      adjust their foraging behavior according to these signals. In insects, such cues
      are mainly chemical, derived from the host plant or the prey itself. The aphid
      alarm pheromone, (E)-beta-farnesene (EBF), is believed to be such a cue, because
      several aphid enemies are able to perceive EBF and show attractant behavior.
      These studies are, however, based mainly on electroantennogram or olfactometer
      assays, and often use unnaturally high pheromone concentrations. It is,
      therefore, unclear if EBF is used to locate prey in the field when only naturally
      released amounts are present. We monitored the frequencies and durations of plant
      visits by aphid natural enemies in the field using long-duration camera
      observations. By placing pheromone releasers emitting no, natural or exaggerated
      amounts of EBF next to small colonies of pea aphids (Acyrthosiphon pisum), we
      analyzed if EBF presence altered long-range foraging behavior of natural enemies.
      Thirteen potential groups of aphid natural enemies were observed in 720 hr of
      analyzed video data. There was no effect of EBF on the number of predator visits
      to an aphid colony, or on predator patch residence times. The number of plant
      visits increased at exaggerated EBF amounts but not at natural EBF levels. We
      conclude that while there may be potential for use of high EBF concentrations for
      agricultural pest management strategies, an ecological role of EBF as a kairomone
      in a natural context is doubtful.

PMID- 25779876
TI  - Do elderly patients benefit from enrollment into Phase I Trials?
AB  - BACKGROUND: Despite the significant burden of cancer in the older population,
      their outcomes in the context of phase I studies have been poorly studied. While
      the Royal Marsden Hospital (RMH) prognostic score (albumin, lactate dehydrogenase
      [LDH], number of metastatic sites) is validated in this setting, its utility
      among the elderly is uncertain. METHODS: A total of 296 consecutive patients who
      were treated in 20 phase I trials from 2005 to 2012 in our unit were analysed.
      Clinical characteristics and outcomes between young (<65, n=202) and older
      patients (>=65, n=94) were compared. RESULTS: The median age of the older
      patients was 69 years (65-84) and 71% were males. Although elderly patients had
      more co-morbidities and lower albumin levels at baseline, there was no
      significant difference in survival (8.8 months versus 9.9 months, p=0.68) and
      clinical benefit rate (69% versus 56%, p=0.07) compared to younger patients after
      median follow-up of 7.1 months (0.36-50.6 months). Age (p=0.23) did not have any
      bearing on occurrence of grade 3/4 toxicities. Twenty-six percent of elderly
      patients experienced grade 3/4 toxicities. The prognostic factors for overall
      survival (OS) identified in multivariate analysis were prior lines of
      chemotherapy (0-2 versus >=3), baseline sodium levels (>=135 versus <135 mmol/L)
      and platelet levels (<=400 versus >400*10(9)). We developed a risk nomogram based
      on the factors prognostic of survival with concordance index of 0.65. The RMH
      model yielded a concordance index of 0.635. CONCLUSION: Elderly patients enrolled
      into phase I clinical trials had similar survival outcomes and toxicity profiles
      compared to younger patients. Risk scoring models to aid patient selection need
      further clarification.

PMID- 25779877
TI  - Review of potential improvements using MRI in the radiotherapy workflow.
AB  - The goal of modern radiotherapy is to deliver a lethal amount of dose to tissue
      volumes that contain a significant amount of tumour cells while sparing
      surrounding unaffected or healthy tissue. Online image guided radiotherapy with
      stereotactic ultrasound, fiducial-based planar X-ray imaging or helical/conebeam
      CT has dramatically improved the precision of radiotherapy, with moving targets
      still posing some methodical problems regarding positioning. Therefore,
      requirements for precise target delineation and identification of functional body
      structures to be spared by high doses become more evident. The identification of
      areas of relatively radioresistant cells or areas of high tumor cell density is
      currently under development. This review outlines the state of the art of MRI
      integration into treatment planning and its importance in follow up and the
      quantification of biological effects. Finally the current state of the art of
      online imaging for patient positioning will be outlined and indications will be
      given what the potential of integrated radiotherapy/online MRI systems is. 

PMID- 25779878
TI  - Early myoclonic encephalopathy in 9q33-q34 deletion encompassing STXBP1 and
      SPTAN1.
AB  - Deletions in the 9q33-q34 region have been reported in patients with early onset
      epileptic encephalopathy, but a consistent phenotype has yet to emerge. We report
      on the diagnosis of a de novo 9q33-q34.12 microdeletion of 4 Mb in a 15-month-old
      girl presenting with severe psychomotor delay, facial dysmorphisms, thin corpus
      callosum and early myoclonic encephalopathy. This deletion encompasses 101 RefSeq
      genes, including the four autosomal dominant genes STXBP1, SPTAN1, ENG and TOR1A.
      We discuss genetic, clinical and epileptic features comparing our patient with
      those previously reported in the literature. 

PMID- 25779880
TI  - Assessing the fit of biotic ligand model validation data in a risk management
      decision context.
AB  - Biotic ligand models (BLMs) have advanced the ability to predict the
      concentrations of metals in surface waters likely to harm aquatic organisms. BLMs
      have been developed for several metals including Cu, Zn, Cd, and Ag.
      Additionally, the US Environmental Protection Agency has published guidance on
      the use of a BLM to develop water quality criteria for Cu. To validate the
      predictive performance of many BLMs, model predictions based on test water
      quality have been compared with corresponding laboratory toxicity measurements.
      Validation results are typically described in the published literature in terms
      of the proportion of predicted effect concentrations that fall within a factor of
      2 of measured values. In this article, an alternative is presented using a
      receiver operating characteristics approach and regression prediction limit
      analyses, quantifying the probabilities of true and false predictions of excess
      toxicity risk based on toxic unit calculations and a risk management threshold of
      1. The approaches are applied to a published Zn BLM and 3 simulated data sets
      that reflect attributes of other published BLM validation data. The overall
      accuracy of the unified Zn BLM is estimated to be 80% to 90%, and analyses of
      simulated data suggest a similar level of accuracy for other published BLMs.
      Further application of these validation methods to other BLMs may provide more
      complete and transparent information on their possible predictive value when used
      in the management of risks due to aqueous metals.

PMID- 25779879
TI  - Losartan increases bone mass and accelerates chondrocyte hypertrophy in
      developing skeleton.
AB  - Angiotensin receptor blockers (ARBs) are a group of anti-hypertensive drugs that
      are widely used to treat pediatric hypertension. Recent application of ARBs to
      treat diseases such as Marfan syndrome or Alport syndrome has shown positive
      outcomes in animal and human studies, suggesting a broader therapeutic potential
      for this class of drugs. Multiple studies have reported a benefit of ARBs on
      adult bone homeostasis; however, its effect on the growing skeleton in children
      is unknown. We investigated the effect of Losartan, an ARB, in regulating bone
      mass and cartilage during development in mice. Wild type mice were treated with
      Losartan from birth until 6 weeks of age, after which bones were collected for
      microCT and histomorphometric analyses. Losartan increased trabecular bone volume
      vs. tissue volume (a 98% increase) and cortical thickness (a 9% increase) in 6
      weeks old wild type mice. The bone changes were attributed to decreased
      osteoclastogenesis as demonstrated by reduced osteoclast number per bone surface
      in vivo and suppressed osteoclast differentiation in vitro. At the molecular
      level, Angiotensin II-induced ERK1/2 phosphorylation in RAW cells was attenuated
      by Losartan. Similarly, RANKL-induced ERK1/2 phosphorylation was suppressed by
      Losartan, suggesting a convergence of RANKL and angiotensin signaling at the
      level of ERK1/2 regulation. To assess the effect of Losartan on cartilage
      development, we examined the cartilage phenotype of wild type mice treated with
      Losartan in utero from conception to 1 day of age. Growth plates of these mice
      showed an elongated hypertrophic chondrocyte zone and increased Col10a1
      expression level, with minimal changes in chondrocyte proliferation. Altogether,
      inhibition of the angiotensin pathway by Losartan increases bone mass and
      accelerates chondrocyte hypertrophy in growth plate during skeletal development.

PMID- 25779881
TI  - Monoclonal anti-transferrin antibody: a paradigm for better understanding of iron
      metabolism.

PMID- 25779882
TI  - Microsurgery in 46 cases with total hand degloving injury.
AB  - OBJECTIVE: To summarize the characteristics of total hand degloving injury and
      investigate the curative effect of microsurgery. METHODS: A total of 46 patients
      with total hand degloving injury were enrolled in this study. The injury
      classification and treatment methods were as follows: Type I (11 cases), treated
      by replantation of the gloved skin; Type II (6 cases), treated by reconstruction
      using thumb wrap-around flap and second toe; Type III (4 cases), treated by
      reconstruction using bilateral second toe with dorsal foot flap; Type IV (9
      cases), treated by replantation in situ or reconstruction; Type V (16 cases),
      treated by replantation or abdominal flap reconstruction. RESULTS: Of the
      patients who received Type I treatment, five completely survived, whereas eight
      had finger necrosis. In Type II, both the reconstructed fingers and hand flaps
      survived. For four patients who received Type III treatment, eight reconstructed
      fingers survived. In Type IV, two patients with reconstructed fingers survived,
      whereas the six with replantation in situ had necrosis of the partial palmar or
      hand dorsum skin. In Type V, nine patients with reconstructed fingers survived,
      and five cases with abdominal skin flap reconstruction and one case with
      anterolateral femoral flap survived. The restoration of hand appearance and
      function was the best in patients who received replantation. For reconstruction
      cases, however, the hand function was recovered to the basic self-care level. In
      cases with abdominal flap reconstruction, the hand function showed poor recovery.
      CONCLUSION: Total hand degloving injury can be classified into different types
      according to the injury degree. The appropriate microsurgical treatment based on
      these types can produce better curative effect.

PMID- 25779883
TI  - A case of rare primary cystic-type squamous cell carcinoma of the breast that
      could be preoperatively diagnosed.
AB  - Primary squamous cell carcinoma of the breast (SCCB) is a rare disease, with a
      worldwide incidence <0.1%. In many cases, it is clinically characterized by rapid
      growth. Cyst formation due to central necrosis of the tumor accompanies its
      growth of the tumor in approximately 60-80% of all cases. Furthermore, it is
      considered difficult to diagnose SCCB solely on the basis of findings from
      diagnostic imaging. For large intracystic tumors, mammotome biopsy or core needle
      biopsy (CNB) is rarely performed. Instead, fine-needle aspiration (FNA) targeted
      at the tumor inside the cyst is often performed. The accurate diagnosis rate of
      SCCB using FNA is lower than that for ordinary-type breast cancer. If the cyst is
      large, the solid tumor shadow outside the cyst behind or around the cyst may be
      masked or hidden by the large cyst, which can sometimes yield an unclear view of
      the tumor shadow or make it impossible to visualize the shadow. In the present
      case, the contents within the cyst were completely aspirated and collected during
      the first step (FNA), thereby yielding a clearer, complete view of the solid
      tumor located outside the cyst. Thus, the subsequent step (CNB) was able to be
      performed in a more accurate and reliable manner. The combined use of FNA and CNB
      proved to be useful in making a preoperative diagnosis of SSCB accompanying a
      cyst.

PMID- 25779884
TI  - Transcervical diverticulectomy for Killian-Jamieson diverticulum.
AB  - Surgery for Killian-Jamieson diverticulum of the esophagus is scarcely reported
      in the literature owing to the rarity of this entity. This is a case report of
      such a diverticulum and a description of the transcervical diverticulectomy that
      we performed on a 49-year-old lady. The patient was investigated for symptoms of
      gastroesophageal reflux disease and was diagnosed with a left-sided Killian
      Jamieson diverticulum.

PMID- 25779885
TI  - The role of prophylactic cefazolin in the prevention of infection after various
      types of abdominal wall hernia repair with mesh.
AB  - OBJECTIVE: There are controversies about the benefits of prophylactic antibiotics
      in the prevention of postoperative surgical site infection (SSI) in mesh
      herniorrhaphy for a long time. This study aimed to evaluate the effectiveness and
      efficacy of systemic prophylactic cefazolin in prevention of wound infection in
      various types of hernia repair with mesh materials. METHODS: This is a
      prospective randomized control study. We evaluated wound infection rates in 395
      patients with various kinds of hernia who underwent elective mesh repair using
      polypropylene mesh from 2007 to 2011. A total of 237 (60.0%) patients received
      prophylactic cefazolin (study group) and the remaining 158 (40.0%) patients did
      not receive any prophylactic antibiotics (control group). Patients were followed
      for infection at the following periods after the operation by an independent
      surgeon: 10 days, 30 days, 12 months, and then annually for at least 2 years.
      RESULTS: Eight (2.03%) patients had infection in the site of surgery [2 (1.27%)
      in the control group and 6 (2.53%) in the study group]. The distribution of
      infection was not significantly different between the two groups (p = 0.364). The
      superficial infections were managed by drainage and irrigation. One patient from
      the study group developed deep SSI and was readmitted and subsequently received
      antibiotic therapy, drainage, and debridement. CONCLUSION: Preoperative
      administration of single-dose cefazolin for prosthetic hernia repairs did not
      markedly decrease the risk of wound infection. Our results do not support the use
      of cefazolin as a prophylactic antibiotic for various kinds of abdominal wall
      hernia repair with mesh.

PMID- 25779886
TI  - A retrospective study of anastomotic leakage between patients with and without
      vascular enhancement of esophageal reconstructions with colon interposition:
      Thammasat University Hospital experience.
AB  - BACKGROUND: Anastomotic leakage is a common complication after operative
      reconstruction with colon interposition in corrosive esophageal injury patients.
      Because the underlying causes are ischemic in nature, vascular enhancement would
      resolve this complication. OBJECTIVE: To compare the incidence of anastomotic
      leakage between patients with and without vascular enhancement of esophageal
      reconstructions with colon interposition. MATERIALS AND METHODS: This is a
      retrospective comparative study between patients with and without vascular
      enhancement during corrosive esophageal reconstructions with colon interposition
      in Thammasat University Hospital from January 2004 to December 2012. RESULTS:
      Twenty-five adult patients who received esophageal reconstructions with colon
      interposition for corrosive esophageal injury were included in this study. Eleven
      of these patients also received vascular enhancement (classified as the "with
      vascular enhancement" group) during the reconstruction, whereas the remaining 14
      patients did not (classified as the "without vascular enhancement" group). There
      was no significant difference in baseline characteristics of the patients between
      the two groups (i.e., sex, age, and preoperative hematocrit and serum albumin
      levels). There was also no significant difference in the leakage rate between the
      two groups: 35.7% (5/14) and 9% (1/11) in the without and with vascular
      enhancement groups, respectively (p = 0.180). However, in the "with vascular
      enhancement" group, the operative time was significantly longer (7.8 hours vs.
      6.4 hours; an additional 1.4 hours), whereas length of hospital stay was shorter
      (18.3 days vs. 28.1 days; reduced by 9.8 days) compared with the other group.
      CONCLUSIONS: Patients who received vascular enhancement along with colon
      interposition had a lower incidence of anastomotic leakage; however, there was no
      significant difference between the two groups in this study. Thus, further
      studies with a large sample size should be conducted in this regard.

PMID- 25779887
TI  - A novel data collection and monitoring system for health status measures in
      patients undergoing lateral internal sphincterotomy: The Knowledge Program (TKP).
AB  - BACKGROUND/OBJECTIVE: The Knowledge Program (TKP) allows prospective data
      collection during routine clinical practice. The aim of this study was to
      evaluate the efficacy and feasibility of TKP for capturing and monitoring health
      status measures in patients undergoing lateral internal sphincterotomy (LIS).
      METHODS: TKP data of patients undergoing LIS from December 2008 to May 2013 were
      retrieved. Health status measures including the Cleveland Global Quality of Life
      (CGQL), European Quality of Life Index (EQ-5D), Fecal Incontinence Severity Index
      (FISI), anorectal pain scores, and satisfaction questions were evaluated in the
      study. RESULTS: A total of 500 patients underwent LIS within the study period.
      Overall patient numbers responding to the health status measures in the pre- and
      postoperative period were as follows: CGQL: 112 preoperatively, 53
      postoperatively; EQ-5D: 112 preoperatively, 55 postoperatively; FISI: 102
      preoperatively, 30 postoperatively; and anorectal pain score: 107 preoperatively,
      45 postoperatively. Among the responders, the number of patients who completed
      the health status measures both pre- and postoperatively was as follows: EQ-5D:
      31, CGQL: 28, anorectal pain: 24, and FISI: 15. A total of 30 patients completed
      postoperative satisfaction and recommendation questions. Postoperative earliest
      (p = 0.02) and most recent (p = 0.01) anorectal pain visual analog scores were
      significantly lower than the preoperative measurements. The earliest
      postoperative EQ-5D scores were significantly higher than their preoperative
      values (p = 0.02). The majority of patients who completed the surveys said they
      were satisfied (70% and 67%) and would recommended (73% and 70%) LIS to others
      undergoing postoperative earliest and most recent follow up. CONCLUSION: LIS
      reduces anorectal pain without worsening quality of life. TKP captures
      information directly from patients and records it to a database which may reduce
      the risk of information loss or alteration.

PMID- 25779889
TI  - Defect/oxygen assisted direct write technique for nanopatterning graphene.
AB  - High resolution nanopatterning of graphene enables manipulation of electronic,
      optical and sensing properties of graphene. In this work we present a
      straightforward technique that does not require any lithographic mask to etch
      nanopatterns into graphene. The technique relies on the damaged graphene to be
      etched selectively in an oxygen rich environment with respect to non-damaged
      graphene. Sub-40 nm features were etched into graphene by selectively exposing it
      to a 100 keV electron beam and then etching the damaged areas away in a
      conventional oven. Raman spectroscopy was used to evaluate the extent of damage
      induced by the electron beam as well as the effects of the selective oxidative
      etching on the remaining graphene. 

PMID- 25779888
TI  - The relationship between dietary protein consumption and risk of fracture: a
      subgroup and dose-response meta-analysis of prospective cohort studies.
AB  - It is still debate of the relationship between the dietary protein consumption
      and risk of fracture. We searched Medline and Embase to assess the effects of
      dietary protein consumption on risk of fracture. Twelve prospective cohort
      studies with 407,104 participants were included, higher total protein consumption
      may be decrease 11% risk of hip fractures, with adj. RR of 0.89 (0.82, 0.97), no
      significant difference was found for total protein and risk of all fractures and
      limb fracture; for animal protein consumption and risk of all fractures and hip
      fracture, with adj.RR of 0.79 (032, 1.96) and 1.04 (0.70, 1.54); for vegetable
      protein consumption and risk of all fractures, hip fracture and limb fractures
      with adj.RR of 0.77 (0.52, 1.12), 1.00 (0.53, 1.91), and 0.94 (0.40, 2.22), the
      subgroup of vegetable protein consumption and risk of all fractures of
      postmenopausal women with adj.RR of 0.78(0.52,1.16). Dose-response meta-analysis
      the relationship of total/animal/vegetable protein and hip fracture was
      consistent to the results of forest plot, the line of total protein and hip
      fracture was below the Y = 1.0 line. This meta-analysis showed that total dietary
      protein consumption may be decrease the risk of hip fracture, but not for animal
      or vegetable protein. 

PMID- 25779890
TI  - A Mathematical Framework for Understanding Four-Dimensional Heterogeneous
      Differentiation of CD4+ T Cells.
AB  - At least four distinct lineages of CD4+ T cells play diverse roles in the immune
      system. Both in vivo and in vitro, naive CD4+ T cells often differentiate into a
      variety of cellular phenotypes. Previously, we developed a mathematical framework
      to study heterogeneous differentiation of two lineages governed by a mutual
      inhibition motif. To understand heterogeneous differentiation of CD4+ T cells
      involving more than two lineages, we present here a mathematical framework for
      the analysis of multiple stable steady states in dynamical systems with multiple
      state variables interacting through multiple mutual-inhibition loops. A
      mathematical model for CD4+ T cells based on this framework can reproduce known
      properties of heterogeneous differentiation involving multiple lineages of this
      cell differentiation system, such as heterogeneous differentiation of TH1-TH2,
      TH1-TH17 and iTReg-TH17 under single or mixed types of differentiation stimuli.
      The model shows that high concentrations of differentiation stimuli favor the
      formation of phenotypes with co-expression of lineage-specific master regulators.

PMID- 25779891
TI  - Expression of Mitochondria-Associated Genes (PPARGC1A, NRF-1, BCL-2 and BAX) in
      Follicular Development and Atresia of Goat Ovaries.
AB  - Most follicles undergo atresia during the developmental process. Follicular
      atresia is predominantly regulated by apoptosis of granulosa cells, but the
      mechanism underlying apoptosis via the mitochondria-dependent apoptotic pathway
      is unclear. We aimed to investigate whether the mitochondria-associated genes
      peroxisome proliferator-activated receptor-gamma, coactivator1-alpha (PPARGC1A),
      nuclear respiratory factor-1 (NRF-1), B-cell CLL/lymphoma 2 (BCL-2) and BCL2
      associated X protein (BAX) played a role in follicular atresia through this
      pathway. The four mitochondria-associated proteins (PGC-1alpha, which are encoded
      by the PPARGC1A gene, NRF-1, BCL-2 and BAX) mainly expressed in granulosa cells.
      The mRNA and protein levels of PPARGC1A/PGC-1alpha and NRF-1 in granulosa cells
      increased with the follicular development. These results showed that these genes
      may play a role in the regulation of the follicular development. In addition,
      compared with healthy follicles, the granulosa cell in atretic follicles had a
      reduced expression of NRF-1, increased BAX expression and increased ratio of BAX
      to BCL-2 expression. These results suggested that changes of the mitochondria
      associated gene expression patterns in granulosa cells may lead to follicular
      atresia during goat follicle development. 

PMID- 25779892
TI  - The effect of pelvic floor muscle training on sexual function in men with lower
      urinary tract symptoms after stroke.
AB  - BACKGROUND: Erectile dysfunction and lower urinary tract symptoms (LUTS) are
      common sequelae in men after stroke. OBJECTIVE: The objective of this study was
      to evaluate the effect of pelvic floor muscle training (PFMT) on measured
      erectile function as an indicator of sexuality in men with LUTS after stroke.
      METHOD: A sample of 516 men with stroke was invited to participate in this single
      blinded, randomized controlled trial according to in- and exclusion criteria.
      This resulted in 31 participants who were randomized to either a Treatment Group
      (n = 16) or a Control Group (n = 15). The intervention included 12?weeks of PFMT.
      The effect was measured on the International Index of Erectile Function (IIEF-5)
      questionnaire. RESULTS: Thirty participants (median age: 68 years; interquartile
      range: 60-74 years) completed the study, 15 in each group. The results of the
      IIEF-5 sum score showed a significant improvement (P < 0.04) from pre-test to
      post-test in the Treatment Group, but not in the Control Group. Within pre-test
      and 6-month follow-up, the median sum score decreased in both groups, worsened in
      the Control Group [Treatment Group, 3 (17%) versus Control Group, 5 (31%)]. There
      were differences between the groups at post-test and at follow-up, but they were
      not statistically significant. CONCLUSION: The results showed that, as measured
      by erectile function in men with LUTS after stroke, PFMT may have short-term and
      long-term effect, although no statistically significant effect was demonstrated
      between the groups.

PMID- 25779893
TI  - Singlet-triplet gaps in polyacenes: a delicate balance between dynamic and static
      correlations investigated by spin-flip methods.
AB  - Over the last few years people have been interested in the process of singlet
      fission, owing to its relevance to solar cell technology. The energetics of
      singlet fission is intimately related to singlet-triplet (ST) gaps and energies
      of singlet excited states. However, accurate calculations of ST gaps in
      polyacenes are complicated due to near degeneracies in the pi orbitals, and
      therefore, have been quite challenging. The spin-flip equation-of-motion coupled
      cluster (SF-EOM-CC) and its perturbative approximation have been shown to
      correctly treat situations involving electronic degeneracies and near
      degeneracies. In this work, we use various spin-flip methods to benchmark the ST
      gaps of small polyacenes and show that the error in the ST gaps with respect to
      the experiment is small and does not increase appreciably with the system size.
      The diradical and polyradical character of the polyacene ground states increase
      with the system size. However, for the small polyacenes the open-shell character
      of the ground state is still small enough to be treated using single reference
      methods. 

PMID- 25779894
TI  - Imbalanced functional link between executive control network and reward network
      explain the online-game seeking behaviors in Internet gaming disorder.
AB  - Literatures have shown that Internet gaming disorder (IGD) subjects show impaired
      executive control and enhanced reward sensitivities than healthy controls.
      However, how these two networks jointly affect the valuation process and drive
      IGD subjects' online-game-seeking behaviors remains unknown. Thirty-five IGD and
      36 healthy controls underwent a resting-states scan in the MRI scanner.
      Functional connectivity (FC) was examined within control and reward network seeds
      regions, respectively. Nucleus accumbens (NAcc) was selected as the node to find
      the interactions between these two networks. IGD subjects show decreased FC in
      the executive control network and increased FC in the reward network when
      comparing with the healthy controls. When examining the correlations between the
      NAcc and the executive control/reward networks, the link between the NAcc -
      executive control network is negatively related with the link between NAcc -
      reward network. The changes (decrease/increase) in IGD subjects' brain synchrony
      in control/reward networks suggest the inefficient/overly processing within
      neural circuitry underlying these processes. The inverse proportion between
      control network and reward network in IGD suggest that impairments in executive
      control lead to inefficient inhibition of enhanced cravings to excessive online
      game playing. This might shed light on the mechanistic understanding of IGD. 

PMID- 25779895
TI  - Emergency preparedness of families of children with developmental disabilities:
      what public health and safety emergency planners need to know.
AB  - OBJECTIVE: To assess the emergency preparedness knowledge, behaviors, and
      training needs of families of children with developmental disabilities (DD).
      DESIGN: An online survey. PARTICIPANTS: A sample of 314 self-selecting US
      parents/guardians of children with DD, aged birth-21 years. MAIN OUTCOME
      MEASURES: 1) Preparedness self-assessment; 2) self-report regarding the extent to
      which families followed 11 specific preparedness action steps derived from
      publicly available preparedness guides; and 3) parent training and support needs.
      RESULTS: Although most participants assessed themselves to be somewhat to
      moderately well prepared, even those who reported being "very well prepared" had
      taken fewer than half of 11 recommended action steps. Most participants expressed
      a need for preparedness support; virtually all the respondents felt that training
      was either important or very important. CONCLUSIONS: Children with disabilities
      are known to be particularly vulnerable to negative disaster impacts. Overall,
      parents in this study appeared under-prepared to meet family disaster needs,
      although they recognized its importance. The results suggest opportunities and
      methods for public health and safety planning, education and outreach to parents
      of children with DD who would benefit from targeted training such as information
      and skill building to develop effective family preparedness plans and connections
      to local emergency management and responders.

PMID- 25779896
TI  - Evaluation of emergency drug releases from the Centers for Disease Control and
      Prevention Quarantine Stations.
AB  - The Centers for Disease Control and Prevention (CDC) Quarantine Stations
      distribute select lifesaving drug products that are not commercially available or
      are in limited supply in the United States for emergency treatment of certain
      health conditions. Following a retrospective analysis of shipment records, the
      authors estimated an average of 6.66 hours saved per shipment when drug products
      were distributed from quarantine stations compared to a hypothetical centralized
      site from CDC headquarters in Atlanta, GA. This evaluation supports the continued
      use of a decentralized model which leverages CDC's regional presence and
      maximizes efficiency in the distribution of lifesaving drugs. 

PMID- 25779897
TI  - Predisaster integration of community emergency response teams.
AB  - OBJECTIVE: The Community Emergency Response Team (CERT) program has been
      increasingly used within local emergency management systems since the United
      States' Federal Emergency Management Agency (FEMA) adopted and began promoting
      the program in 1993. The objective of this study was to explore the integration
      of CERT programs within local emergency management systems predisaster. DESIGN:
      Qualitative, semistructured telephone interviews were used to collect data from a
      purposive sample of CERT program coordinators. SETTING: Telephone interviews were
      conducted with CERT program coordinators in FEMA Region VII (Iowa, Kansas,
      Missouri, and Nebraska). SUBJECTS, PARTICIPANTS: Twenty-five local county
      emergency managers participated in this study. RESULTS: This study found that the
      integration of CERTs varied significantly. The extent to which most teams were
      integrated allowed them to be placed along an integration continuum and
      classified as one of three types including Least Integrated, Somewhat Integrated,
      and Highly Integrated. Other team characteristics seemed to covary with the team
      integration. A phenomenon of team Piggy Backing-where the integration of the team
      was no longer relevant-was also found. CONCLUSIONS: This study concludes by
      making a key recommendation that could benefit any CERT-add a module to the CERT
      training curriculum designed to integrate the individuals associated with the
      CERT program within their local emergency management system.

PMID- 25779898
TI  - Emergency managers as change agents: recognizing the value of management,
      leadership, and strategic management in the disaster profession.
AB  - This article discusses the influence of management theory, some principles of
      leadership, four strategic management considerations, that are applied to
      emergency management, allow emergency managers to transform their followers,
      organizations, and communities at large. The authors argue that in the past there
      has been little recognition of the value, or application, of these three areas of
      emphasis in the disaster profession. Using more of these principles, emergency
      managers may transform into transformational change agents who make a difference
      in their followers' lives, who themselves transform other people and improve
      emergency management. 

PMID- 25779899
TI  - The variational effects of jurisdictional attributes on hazard mitigation
      planning costs.
AB  - Under the Disaster Mitigation Act of 2000 and Federal Emergency Management
      Agency's subsequent Interim Final Rule, the requirement was placed on local
      governments to author and gain approval for a Hazard Mitigation Plan (HMP) for
      the areas under their jurisdiction. Low completion percentages for HMPs-less than
      one-third of eligible governments-were found by an analysis conducted 3 years
      after the final deadline for the aforementioned legislation took place. Follow-up
      studies showed little improvement at 5 and 8 years after the deadline. Based on
      these results, a previous study hypothesized that the cost of creating a HMP
      might be an influential factor in explaining why most jurisdictions had failed to
      write or gain approval for a HMP. The frequency of natural hazards experienced by
      the planning jurisdiction, the number of jurisdictions participating in the plan,
      and the population and population density were found to explain more than half of
      the variation in HMP costs. This study is a continuation of that effort, finding
      that there are significant differences in cost both across ranges of values for
      the jurisdictional attributes and single-jurisdictional versus
      multijurisdictional plans. 

PMID- 25779900
TI  - The general use of outdoor warning sirens: a preliminary survey of emergency
      managers.
AB  - With more direct, personal warning systems becoming popular, the continued
      maintenance of older warning systems, such as outdoor warning sirens, may be
      jeopardized as emergency managers (EMs) seek to optimize their limited budgets.
      However, the extent to which sirens are embedded into the American landscape and
      culture argues against their removal. To better quantify the distribution and use
      of outdoor warning sirens, an international survey of EMs was conducted to learn
      more about where siren systems are deployed and how they are operated.
      Approximately 593 respondents started the 31 question survey with 383 completing
      it. Questions were asked regarding siren network size, alternative warning
      systems, siren use and capabilities, and testing. For those without sirens, a
      series of questions were asked for why sirens were not used. In general, a lack
      of perceived threat, high costs, and large geographic area kept some
      jurisdictions from installing sirens. Of those that operate siren networks, half
      of networks are small (<=10 sirens), while a small percentage of jurisdictions
      (6.3 percent) operate very large networks (>100). A large majority of respondents
      expected to maintain or expand their networks within the next 5 years. Three
      quarters of respondents use additional warning systems. Nearly half of
      respondents use sirens for nonweather applications, and nearly two-thirds have
      the capability to use multiple sound alerts. Overall, sirens remain a popular
      tool for warning on a variety of local hazards though how the sirens are operated
      and tested vary widely by jurisdiction. 

PMID- 25779901
TI  - Public health incident management: logistical and operational aspects of the 2009
      initial outbreak of H1N1 influenza in Mexico.
AB  - Hosting an international outbreak response team can pose a challenge to
      jurisdictions not familiar with incident management frameworks. Basic principles
      of team forming, organizing, and executing mission critical activities require
      simple and flexible communication that can be easily understood by the host
      country's public health leadership and international support agencies.
      Familiarity with incident command system principles before a public health
      emergency could save time and effort during the initial phases of the response
      and aid in operationalizing and sustaining complex field activities throughout
      the response. The 2009 initial outbreak of H1N1 in Mexico highlighted the
      importance of adequately organizing and managing limited resources and expertise
      using incident management principles. This case study describes logistical and
      operational aspects of the response and highlights challenges faced during this
      response that may be relevant to the organization of public health responses and
      incidents requiring international assistance and cooperation.

PMID- 25779902
TI  - Differential effects of two probiotics on the risks of eczema and atopy
      associated with single nucleotide polymorphisms to Toll-like receptors.
AB  - BACKGROUND: There is strong evidence to support a genetic predisposition to
      eczema and more recently studies have suggested that probiotics might be used to
      prevent eczema by modifying the expression of putative allergy-associated genes.
      The aim of this present study was to investigate whether two probiotics,
      Lactobacillus rhamnosus HN001 (HN001) and Bifidobacterium animalis subsp. lactis
      HN019 (HN019), can modify the known genetic predisposition to eczema conferred by
      genetic variation in the Toll-like receptor (TLR) genes in a high-risk infant
      population. METHODS: We selected 54 SNPs in the Toll-like receptor genes. These
      SNPs were analysed in 331 children of sole European ancestry as part of a double
      blind, randomized, placebo-controlled trial examining the effects of HN001 and
      HN019 supplementation on eczema development and atopic sensitization. RESULTS:
      The data showed that 26 TLR SNPs interacted with HN001 resulting in a
      significantly reduced risk of eczema, 18 for eczema severity as defined by SCORAD
      >= 10 and 20 for atopic sensitization compared to placebo. There were only two
      SNPs that interacted with HN019 resulting in a reduced risk of eczema, eczema
      severity or atopy. CONCLUSIONS: This is the first study to show that the negative
      impact of specific TLR genotypes may be positively affected by probiotic
      supplementation. HN001 exhibits a much stronger effect than HN019 in this
      respect.

PMID- 25779903
TI  - Impact of Ambulatory Blood Pressure Monitoring on Reclassification of
      Hypertension Prevalence and Control in Older People in Spain.
AB  - Ambulatory blood pressure monitoring (ABPM) accurately classifies blood pressure
      (BP) status but its impact on the prevalence and control of hypertension is
      little known. The authors conducted a cross-sectional study in 2012 among 1047
      individuals 60 years and older from the follow-up of a population cohort in
      Spain. Three casual BP measurements and 24-hour ABPM were performed under
      standardized conditions. Approximately 68.8% patients were hypertensive based on
      casual BP (>=140/90 mm Hg or current BP medication use) and 62.1% based on 24
      hour ABPM (>=130/80 mm Hg or current BP medication use) (P=.009). The proportion
      of patients with treatment-eligible hypertension who met BP goals increased from
      37.4% based on the casual BP target to 54.1% based on the 24-hour BP target
      (absolute difference, 16.7%; P<.01). These results were consistent across
      alternative BP thresholds. Therefore, compared with casual BP, 24-hour ABPM led
      to a reduction in the proportion of older patients recommended for hypertension
      treatment and a substantial increase in the proportion of those with hypertension
      control.

PMID- 25779904
TI  - The association between the density of retail tobacco outlets, individual smoking
      status, neighbourhood socioeconomic status and school locations in New South
      Wales, Australia.
AB  - AIM: We explored the association between the density of tobacco outlets and
      neighbourhood socioeconomic status, and between neighbourhood tobacco outlet
      density and individual smoking status. We also investigated the density of
      tobacco outlets around primary and secondary schools in New South Wales (NSW).
      METHODS: We calculated the mean density of retail tobacco outlets registered in
      NSW between 2009 and 2011, using kernel density estimation with an adaptive
      bandwidth. We used generalised ordered logistic regression model to explore the
      association between socioeconomic status and density of tobacco outlets. The
      association between neighbourhood tobacco outlet density and individuals' current
      smoking status was investigated using random-intercept generalised linear mixed
      models. We also calculated the median tobacco outlet density around NSW schools.
      RESULTS: More disadvantaged Census Collection Districts (CDs) were significantly
      more likely to have higher tobacco outlet densities. After adjusting for
      neighbourhood socioeconomic status and participants' age, sex, country of birth
      and Aboriginal status, neighbourhood mean tobacco outlet density was
      significantly and positively associated with individuals' smoking status. The
      median of tobacco outlet density around schools was significantly higher than the
      state median. CONCLUSION: Policymakers could consider exploring a range of
      strategies that target tobacco outlets in proximity to schools, in more
      disadvantaged neighbourhoods and in areas of existing high tobacco outlet
      density.

PMID- 25779905
TI  - Landscape risk factors for Lyme disease in the eastern broadleaf forest province
      of the Hudson River valley and the effect of explanatory data classification
      resolution.
AB  - This study assessed how landcover classification affects associations between
      landscape characteristics and Lyme disease rate. Landscape variables were derived
      from the National Land Cover Database (NLCD), including native classes (e.g.,
      deciduous forest, developed low intensity) and aggregate classes (e.g., forest,
      developed). Percent of each landcover type, median income, and centroid
      coordinates were calculated by census tract. Regression results from individual
      and aggregate variable models were compared with the dispersion parameter-based
      R(2) (Ralpha(2)) and AIC. The maximum Ralpha(2) was 0.82 and 0.83 for the best
      aggregate and individual model, respectively. The AICs for the best models
      differed by less than 0.5%. The aggregate model variables included forest,
      developed, agriculture, agriculture-squared, y-coordinate, y-coordinate-squared,
      income and income-squared. The individual model variables included deciduous
      forest, deciduous forest-squared, developed low intensity, pasture, y-coordinate,
      y-coordinate-squared, income, and income-squared. Results indicate that regional
      landscape models for Lyme disease rate are robust to NLCD landcover
      classification resolution.

PMID- 25779906
TI  - Maternal anemia associated with walkable distance to healthy food sources in
      Bronx, New York.
AB  - The relationship between walkable access to healthy food sources and risk of
      anemia in pregnancy was evaluated for a cohort of 4678 women who initiated
      prenatal care in the year 2010 at an academic medical center in Bronx, New York.
      After geocoding patient residences, street network distances were obtained for
      the closest healthy food sources, which were identified from multiple databases.
      For lower-income patients, as indicated by Medicaid or lack of health insurance,
      those who lived less than 0.25miles from a healthy food source were less likely
      to be anemic when compared to those who lived farther (adjusted OR=0.65, 95% CI
      0.48, 0.88). Patients with commercial insurance showed no effect. These results
      help to understand how a nutritionally-mediated condition such as anemia during
      pregnancy can be affected by one's built environment, while also highlighting the
      importance of conditioning on socioeconomic status for these types of studies.

PMID- 25779907
TI  - Estimating areas of common risk in low birth weight and infant mortality in
      Namibia: a joint spatial analysis at sub-regional level.
AB  - There is lots of literature documenting a positive association between low birth
      weight (LBW) and infant mortality (IM), however, little is known how the risk of
      LBW and IM are geographically co-distributed. We fitted joint spatial models of
      LBW and IM, and used data from Namibia, to examine their geographical
      variability. We used a Bayesian approach to measure and rank areas according to
      specific and shared risk of LBW and IM. Our findings show some degree of
      similarities in the spatial pattern of LBW and IM, with high risk in the central
      and north-eastern parts of the country. Results suggest a need for comprehensive
      programming of maternal and newborn interventions that reach areas of spatially
      concentrated risk of LBW and IM. It further presents an opportunity for
      generating hypotheses for further research aimed at improving child health,
      especially in higher risk constituencies thus identified. 

PMID- 25779908
TI  - Spatial variation in attributable risks.
AB  - The attributable risk (AR) measures the contribution of a particular risk factor
      to a disease, and allows estimation of disease rates specific to that risk. While
      previous studies consider variability in ARs over demographic categories, this
      paper considers the extent of spatial variability in ARs estimated from
      multilevel data with confounders both at individual and geographic levels. A case
      study considers the AR for diabetes in relation to elevated BMI, and area rates
      for diabetes attributable to excess weight. Contextual adjustment includes known
      area variables, and unobserved spatially clustered influences, while spatial
      heterogeneity (effect modification) is considered in terms of varying effects of
      elevated BMI by neighbourhood deprivation category. The application is to patient
      register data in London, with clear evidence of spatial variation in ARs, and in
      small area diabetes rates attributable to excess weight. 

PMID- 25779909
TI  - Error-based extraction of states and energy landscapes from experimental single
      molecule time-series.
AB  - Characterization of states, the essential components of the underlying energy
      landscapes, is one of the most intriguing subjects in single-molecule (SM)
      experiments due to the existence of noise inherent to the measurements. Here we
      present a method to extract the underlying state sequences from experimental SM
      time-series. Taking into account empirical error and the finite sampling of the
      time-series, the method extracts a steady-state network which provides an
      approximation of the underlying effective free energy landscape. The core of the
      method is the application of rate-distortion theory from information theory,
      allowing the individual data points to be assigned to multiple states
      simultaneously. We demonstrate the method's proficiency in its application to
      simulated trajectories as well as to experimental SM fluorescence resonance
      energy transfer (FRET) trajectories obtained from isolated agonist binding
      domains of the AMPA receptor, an ionotropic glutamate receptor that is prevalent
      in the central nervous system. 

PMID- 25779910
TI  - Surgical treatment of hepatic cystic echinococcosis in patients co-infected with
      HIV/AIDS.
AB  - Co-infections of cystic echinococcosis (CE) and HIV/AIDS is rare. We report four
      CE cases that were HIV positive. Three out of the four patients underwent a
      surgical operation to remove the hydatid cysts in their livers. The operation
      confirmed that in two of the cases their cysts had ruptured. These patients were
      given 3 months of albendazole after the operation. Follow-up showed they were
      remarkably improved in term of their health, although they were still HIV
      antibody positive 6 months after surgical treatment. Interestingly, the treatment
      remarkably increased their CD4+ cell population. We showed that surgery is
      suitable for treating hepatic cystic echinococcosis with HIV/AIDS co-infection. 

PMID- 25779911
TI  - Silver nanowire-embedded PDMS with a multiscale structure for a highly sensitive
      and robust flexible pressure sensor.
AB  - The development of highly sensitive pressure sensors with a low-cost and facile
      fabrication technique is desirable for electronic skins and wearable sensing
      devices. Here a low-cost and facile fabrication strategy to obtain multiscale
      structured elastomeric electrodes and a highly sensitive and robust flexible
      pressure sensor is presented. The principles of spontaneous buckle formation of
      the PDMS surface and the embedding of silver nanowires are used to fabricate the
      multiscale-structured elastomeric electrode. By laminating the multiscale
      structured elastomeric electrode onto the dielectric layer/bottom electrode
      template, the pressure sensor can be obtained. The pressure sensor is based on
      the capacitive sensing mechanism and shows high sensitivity (>3.8 kPa(-1)), fast
      response and relaxation time (<150 ms), high bending stability and high cycle
      stability. The fabrication process can be easily scaled up to produce pressure
      sensor arrays and they can detect the spatial distribution of the applied
      pressure. It is also demonstrated that the fingertip pressure sensing device can
      sense the pressure distribution of each finger, when grabbing an object. 

PMID- 25779912
TI  - Editorial: treat to target in rheumatoid arthritis: good for the joints as well
      as the heart?

PMID- 25779913
TI  - Trauma patterns, symptoms, and complications associated with external auditory
      canal fractures.
AB  - OBJECTIVES/HYPOTHESIS: External auditory canal (EAC) trauma, although rare, can
      have significant long-term adverse outcomes. This study aims to investigate the
      frequency, treatment, and complications of external ear canal injury in
      association with mandibular and temporal bone trauma. STUDY DESIGN: Retrospective
      chart review. METHODS: Computed tomography images with mandibular or temporal
      bone trauma were reviewed for EAC fractures. Patient data were collected from
      initial presentation and subsequent follow-up clinic visits. RESULTS: Thirty-nine
      percent of temporal bone fractures and 3.3% of mandible trauma involved the EAC.
      In particular, 10% of condylar or subcondylar trauma included an EAC fracture (P
      = 0.0006). One patient sustained bilateral EAC fractures despite an isolated,
      unilateral condylar fracture. The most common presenting sign was blood in the
      external auditory canal. Two patients underwent exam under anesthesia and removal
      of debris and stenting as treatment, whereas 42% of the patients were placed on
      otic drops and 5% received packing or a stent. Follow-up data were only available
      for 16% of the patients. Hearing loss from otic capsule involvement or ossicular
      chain disruption were follow-up complaints, and one patient had persistent canal
      stenosis. CONCLUSIONS: External auditory canal trauma is present in a significant
      proportion of mandibular and temporal bone trauma, including both condylar and
      noncondylar fractures with a higher incidence of condylar fractures. One case was
      seen with bilateral EAC fractures despite a unilateral mandibular fracture.
      Complications of these fractures can include hearing loss and canal stenosis;
      however, additional outpatient follow-up is needed to further elucidate long-term
      complications and shape treatment recommendations.

PMID- 25779914
TI  - Cervical joint position sense in neck pain. Immediate effects of muscle vibration
      versus mental training interventions: a RCT.
AB  - BACKGROUND: Impaired cervical joint position sense is a feature of chronic neck
      pain and is commonly argued to rely on abnormal cervical input. If true, muscle
      vibration, altering afferent input, but not mental interventions, should have an
      effect on head repositioning acuity and neck pain perception. AIM: The aim of the
      present study was to determine the short-term effects of neck muscle vibration,
      motor imagery, and action observation on cervical joint position sense and
      pressure pain threshold in people with chronic neck pain. DESIGN: Forty-five
      blinded participants with neck pain received concealed allocation and were
      randomized in three treatment groups. A blinded assessor performed pre- and post
      test measurement. SETTING: Patients were recruited from secondary outpatient
      clinics in the southwest of Germany. POPULATION: Chronic, non specific neck pain
      patients without arm pain were recruited for this study. METHODS: A single
      intervention session of 5 minutes was delivered to each blinded participant.
      Patients were either allocated to one of the following three interventions: (1)
      neck muscle vibration; (2) motor imagery; (3) action observation. Primary
      outcomes were cervical joint position sense acuity and pressure pain threshold.
      Repeated measures ANOVAs were used to evaluate differences between groups and
      subjects. RESULTS: Repositioning acuity displayed significant time effects for
      vibration, motor imagery, and action observation (all P<0.05), but revealed no
      time*group effect. Pressure pain threshold demonstrated a time*group effect
      (P=0.042) as only vibration significantly increased pressure pain threshold
      (P=0.01). CONCLUSION: Although motor imagery and action observation did not
      modulate proprioceptive, afferent input, they nevertheless improved cervical
      joint position sense acuity. This indicates that, against the common opinion,
      changes in proprioceptive input are not prerequisite to improve joint
      repositioning performance. However, the short-term applications of these
      cognitive treatments had no effect on pressure pain thresholds, whereas vibration
      reduced pressure pain thresholds. This implies different underlying mechanisms
      after vibration and mental training. CLINICAL REHABILITATION IMPACT: Mental
      interventions were effective in improving cervical joint position sense and are
      easy to integrate in rehabilitation regimes. Neck muscle vibration is effective
      in improving cervical joint position sense and pressure pain thresholds within 5
      minutes of application.

PMID- 25779915
TI  - Obesity and female malignancies.
AB  - Obesity increases the risk of endometrial and ovarian cancer, and oestrogen
      receptor (ER)-progesterone receptor (PR)-positive postmenopausal breast cancer. A
      modest positive association between body mass index (BMI) and cervical cancer has
      also been found. By contrast, an inverse correlation between BMI and
      premenopausal breast cancer exists. Endogenous sex hormones, insulin
      resistance/hyperinsulinaemia, adipokines, cytokines and chronic inflammation,
      among other factors, may be involved in the promotion of cancer in obese
      patients. Obesity is also associated with an increased risk of cancer recurrence
      and mortality most likely due to suboptimal treatment and/or co-morbidities. It
      is recommended that chemotherapy doses be calculated on the actual body weight
      and that radical surgery be performed as in non-obese patients. The high risk of
      peri-operative complications may be reduced by optimizing preoperative clinical
      conditions. As part of cancer prevention, obese women should be encouraged to
      adopt healthy lifestyles leading to weight loss and to undergo regular cancer
      screening. 

PMID- 25779916
TI  - Real-time conductivity imaging of temperature and tissue property changes during
      radiofrequency ablation: an ex vivo model using weighted frequency difference.
AB  - We demonstrated the feasibility of time difference and weighted frequency
      difference conductivity imaging for real-time monitoring of temperature
      distribution and ablation region estimation during radiofrequency (RF) ablation.
      The electrical conductivity spectrum of biological tissue reflects mobility of
      ions in intra- and extra-cellular fluids and changes in cellular morphology
      induced by heating. The time series conductivity spectra were measured in an ex
      vivo bovine liver by a high-speed electrical impedance tomography (EIT) system.
      The EIT system was protected by filters to suppress RF energy and allow
      interleaved real-time imaging. We recorded time and weighted frequency-difference
      conductivity images and direct temperature variations at the ablation region and
      control region during 8 min ablation and for the following 66 min of cooling.
      Conductivity variation in regions of interest was compared with temperature
      recordings. Contours of conductivity change were visualized and compared to
      estimate the ablation area. EIT images confirmed increase of conductivity at all
      frequencies and loss of frequency conductivity change associated with loss of
      cellular structure. Time difference conductivity images showed changes due to
      both heating during ablation and heat dissipation following ablation together
      with tissue property changes. Weighted frequency-difference images presented
      persistent changes following heating due to the morphological change in the
      ablation zone.

PMID- 25779917
TI  - Expression of human poly (ADP-ribose) polymerase 1 in Saccharomyces cerevisiae:
      Effect on survival, homologous recombination and identification of genes involved
      in intracellular localization.
AB  - The poly (ADP-ribose) polymerase 1 (PARP-1) actively participates in a series of
      functions within the cell that include: mitosis, intracellular signaling, cell
      cycle regulation, transcription and DNA damage repair. Therefore, inhibition of
      PARP1 has a great potential for use in cancer therapy. As resistance to PARP
      inhibitors is starting to be observed in patients, thus the function of PARP-1
      needs to be studied in depth in order to find new therapeutic targets. To gain
      more information on the PARP-1 activity, we expressed PARP-1 in yeast and
      investigated its effect on cell growth and UV induced homologous recombination.
      To identify candidate genes affecting PARP-1 activity and cellular localization,
      we also developed a yeast genome wide genetic screen. We found that PARP-1
      strongly inhibited yeast growth, but when yeast was exposed to the PARP-1
      inhibitor 6(5-H) phenantridinone (PHE), it recovered from the growth suppression.
      Moreover, we showed that PARP-1 produced PAR products in yeast and we
      demonstrated that PARP-1 reduced UV-induced homologous recombination. By genome
      wide screening, we identified 99 mutants that suppressed PARP-1 growth
      inhibition. Orthologues of human genes were found for 41 of these yeast genes. We
      determined whether the PARP-1 protein level was altered in strains which are
      deleted for the transcription regulator GAL3, the histone H1 gene HHO1, the HUL4
      gene, the deubiquitination enzyme gene OTU1, the nuclear pore protein POM152 and
      the SNT1 that encodes for the Set3C subunit of the histone deacetylase complex.
      In these strains the PARP-1 level was roughly the same as in the wild type. PARP
      1 localized in the nucleus more in the snt1Delta than in the wild type strain;
      after UV radiation, PARP-1 localized in the nucleus more in hho1 and pom152
      deletion strains than in the wild type indicating that these functions may have a
      role on regulating PARP-1 level and activity in the nucleus.

PMID- 25779918
TI  - Ferroelectric domain wall motion induced by polarized light.
AB  - Ferroelectric materials exhibit spontaneous and stable polarization, which can
      usually be reoriented by an applied external electric field. The electrically
      switchable nature of this polarization is at the core of various ferroelectric
      devices. The motion of the associated domain walls provides the basis for
      ferroelectric memory, in which the storage of data bits is achieved by driving
      domain walls that separate regions with different polarization directions. Here
      we show the surprising ability to move ferroelectric domain walls of a BaTiO3
      single crystal by varying the polarization angle of a coherent light source. This
      unexpected coupling between polarized light and ferroelectric polarization
      modifies the stress induced in the BaTiO3 at the domain wall, which is observed
      using in situ confocal Raman spectroscopy. This effect potentially leads to the
      non-contact remote control of ferroelectric domain walls by light.

PMID- 25779919
TI  - Corrigendum.

PMID- 25779920
TI  - Retraction note: Predicting new molecular targets for rhein using network
      pharmacology.

PMID- 25779921
TI  - MetaNET--a web-accessible interactive platform for biological metabolic network
      analysis.
AB  - BACKGROUND: Metabolic reactions have been extensively studied and compiled over
      the last century. These have provided a theoretical base to implement models,
      simulations of which are used to identify drug targets and optimize metabolic
      throughput at a systemic level. While tools for the perturbation of metabolic
      networks are available, their applications are limited and restricted as they
      require varied dependencies and often a commercial platform for full
      functionality. We have developed MetaNET, an open source user-friendly platform
      independent and web-accessible resource consisting of several pre-defined
      workflows for metabolic network analysis. RESULT: MetaNET is a web-accessible
      platform that incorporates a range of functions which can be combined to produce
      different simulations related to metabolic networks. These include (i)
      optimization of an objective function for wild type strain,
      gene/catalyst/reaction knock-out/knock-down analysis using flux balance analysis.
      (ii) flux variability analysis (iii) chemical species participation (iv) cycles
      and extreme paths identification and (v) choke point reaction analysis to
      facilitate identification of potential drug targets. The platform is built using
      custom scripts along with the open-source Galaxy workflow and Systems Biology
      Research Tool as components. Pre-defined workflows are available for common
      processes, and an exhaustive list of over 50 functions are provided for user
      defined workflows. CONCLUSION: MetaNET, available at http://metanet.osdd.net ,
      provides a user-friendly rich interface allowing the analysis of genome-scale
      metabolic networks under various genetic and environmental conditions. The
      framework permits the storage of previous results, the ability to repeat analysis
      and share results with other users over the internet as well as run different
      tools simultaneously using pre-defined workflows, and user-created custom
      workflows.

PMID- 25779923
TI  - Chronic unpredictable mild stress induces parallel reductions of 15-PGDH in the
      hypothalamus and lungs in rats.
AB  - Prostaglandin E2 (PGE2) is an important inflammatory mediator and considered to
      be involved in the pathophysiology of depression. Previous studies that
      investigated the role of PGE2 in depression solely concentrated on the
      cyclooxygenase-dependent synthesis of this bioactive lipid. However, enzymes that
      degrade PGE2, such as NAD(+)-dependent 15-hydroxyprostaglandin dehydrogenase (15
      PGDH), have not yet been explored. The present study examined the expression of
      15-PGDH in an animal model of depression. Depressive-like behaviors were measured
      after rats were exposed to chronic unpredictable mild stress (CUMS). 15 PGDH mRNA
      and protein expression and activity and PGE2 levels were detected in the brain
      and lungs in stressed animals. The stressed animals exhibited decreases in body
      weight gain, locomotor activity in the open field, and sucrose preference. The
      hypothalamus and lungs had high baseline 15-PGDH mRNA and protein expression,
      whereas the frontal cortex and hippocampus showed no detectable 15-PGDH mRNA or
      protein expression. 15 PGDH mRNA and protein expression was significantly
      downregulated in the hypothalamus and lungs in stressed rats compared with
      control rats, and the enzymatic activity of 15-PGDH was correlated with protein
      expression levels. PGE2 concentrations in the brain and serum increased in
      stressed rats. These results suggest the loss of 15-PGDH expression in
      depression, and 15-PGDH may be a novel potential pharmacological target for the
      treatment of depression. 

PMID- 25779924
TI  - Obesity is marked by distinct functional connectivity in brain networks involved
      in food reward and salience.
AB  - We hypothesized that brain circuits involved in reward and salience respond
      differently to fasting in obese versus lean individuals. We compared functional
      connectivity networks related to food reward and saliency after an overnight fast
      (baseline) and after a prolonged fast of 48 h in lean versus obese subjects. We
      included 13 obese (2 males, 11 females, BMI 35.4 +/- 1.2 kg/m(2), age 31 +/- 3
      years) and 11 lean subjects (2 males, 9 females, BMI 23.2 +/- 0.5 kg/m(2), age 28
      +/- 3 years). Resting-state functional magnetic resonance imaging scans were made
      after an overnight fast (baseline) and after a prolonged 48 h fast. Functional
      connectivity of the amygdala, hypothalamus and posterior cingulate cortex
      (default-mode) networks was assessed using seed-based correlations. At baseline,
      we found a stronger connectivity between hypothalamus and left insula in the
      obese subjects. This effect diminished upon the prolonged fast. After prolonged
      fasting, connectivity of the hypothalamus with the dorsal anterior cingulate
      cortex (dACC) increased in lean subjects and decreased in obese subjects.
      Amygdala connectivity with the ventromedial prefrontal cortex was stronger in
      lean subjects at baseline, which did not change upon the prolonged fast. No
      differences in posterior cingulate cortex connectivity were observed. In
      conclusion, obesity is marked by alterations in functional connectivity networks
      involved in food reward and salience. Prolonged fasting differentially affected
      hypothalamic connections with the dACC and the insula between obese and lean
      subjects. Our data support the idea that food reward and nutrient deprivation are
      differently perceived and/or processed in obesity.

PMID- 25779925
TI  - The effects of different levels of vitamin E and vitamin C in modified Beltsville
      extender on rooster post-thawed sperm quality.
AB  - Oxidative damage of sperm by means of reactive oxygen species generated by the
      cellular components of semen is one of the main reason of declined motility and
      fertility of sperm during the freeze-thawing process. This study was conducted to
      determine the influence of vitamin C and vitamin E on rooster post-thawed sperm
      motility, viability and malondialdehyde (MDA) level. Semen samples from 10
      sexually-mature Ross 308 breeder roosters were collected and pooled, divided into
      nine equal parts and diluted with modified Beltsville extender containing with no
      antioxidants (control), or containing 100 (C100), 200 (C200), 400 (C400), 800
      (C800) ug/mL vitamin C, and 2 (E2), 5 (E5), 10 (E10) and 15 (E15) ug/mL vitamin
      E. After thawing, total and progressive sperm motility, sperm viability and semen
      MDA level were assessed. The results shown that C200 and E5 extenders resulted in
      higher total motility (p < 0.05) compared to other extenders, with exception of
      E10 extender. Progressive motility was higher in E5 extender (p < 0.05) compared
      to other extenders, with exception of C200 and E10 extenders. Also, C200 and E5
      extenders resulted in higher viability of post-thawed spermatozoa (p < 0.05)
      compared to other extenders. Finally, the results showed that MDA level was lower
      in C100 and C200 extenders compared to other extenders (p < 0.05), with exception
      of E5 extender. In conclusion, the results of the present study demonstrate that
      C200 and E5 can improve the function of post-thawed rooster spermatozoa. 

PMID- 25779926
TI  - Growth and Survival of Mesorhizobium loti Inside Acanthamoeba Enhanced Its
      Ability to Develop More Nodules on Lotus corniculatus.
AB  - The importance of protozoa as environmental reservoirs of pathogens is well
      recognized, while their impact on survival and symbiotic properties of rhizobia
      has not been explored. The possible survival of free-living rhizobia inside
      amoebae could influence bacterial abundance in the rhizosphere of legume plants
      and the nodulation competitiveness of microsymbionts. Two well-characterized
      strains of Mesorhizobium: Mesorhizobium loti NZP2213 and Mesorhizobium huakuii
      symbiovar loti MAFF303099 were assayed for their growth ability within the Neff
      strain of Acanthamoeba castellanii. Although the association ability and the
      initial uptake rate of both strains were similar, recovery of viable M. huakuii
      MAFF303099 after 4 h postinfection decreased markedly and that of M. loti NZP2213
      increased. The latter strain was also able to survive prolonged co-incubation
      within amoebae and to self-release from the amoeba cell. The temperature 28 
      degrees C and PBS were established as optimal for the uptake of Mesorhizobium by
      amoebae. The internalization of mesorhizobia was mediated by the mannose
      dependent receptor. M. loti NZP2213 bacteria released from amoebae developed 1.5
      times more nodules on Lotus corniculatus than bacteria cultivated in an amoebae
      free medium. 

PMID- 25779927
TI  - Sudden death associated with QT interval prolongation and KCNQ1 gene mutation in
      a family of English Springer Spaniels.
AB  - BACKGROUND: A 5-year-old, healthy English Springer Spaniel died suddenly 4 months
      after delivering a litter of 7 puppies. Within 4 months of the dam's death, 3
      offspring also died suddenly. HYPOTHESIS: Abnormal cardiac repolarization, caused
      by an inherited long QT syndrome, is thought to be responsible for arrhythmias
      leading to sudden death in this family. ANIMALS: Four remaining dogs from the
      affected litter and 11 related dogs. METHODS: Physical examination and resting
      ECG were done on the littermates and 9 related dogs. Additional tests on some or
      all littermates included echocardiogram with Doppler, Holter monitoring, and
      routine serum biochemistry. Blood for DNA sequencing was obtained from all 15
      dogs. RESULTS: Three of 4 littermates examined, but no other dogs, had prolonged
      QT intervals with unique T-wave morphology. DNA sequencing of the KCNQ1 gene
      identified a heterozygous single base pair mutation, unique to these 3 dogs,
      which changes a conserved amino acid from threonine to lysine and is predicted to
      change protein structure. CONCLUSIONS AND CLINICAL IMPORTANCE: This family
      represents the first documentation in dogs of spontaneous familial QT
      prolongation, which was associated with a KCNQ1 gene mutation and sudden death.
      Although the final rhythm could not be documented in these dogs, their phenotypic
      manifestations of QT interval prolongation and abnormal ECG restitution suggested
      increased risk for sudden arrhythmic death. The KCNQ1 gene mutation identified is
      speculated to impair the cardiac repolarizing current IKs, similar to KCNQ1
      mutations causing long QT syndrome 1 in humans.

PMID- 25779928
TI  - Trop2 inhibition suppresses the proliferation and invasion of laryngeal carcinoma
      cells via the extracellular signal-regulated kinase/mitogen-activated protein
      kinase pathway.
AB  - The cell surface glycoprotein Trop2 is overexpressed in various types of
      epithelial cancer. Laryngeal carcinoma is one of the most common types of head
      and neck cancer and in a previous study, the expression of Trop2 in laryngeal
      squamous cell carcinoma (LSCC) was identified as an independent prognostic
      factor. However, the biological significance of Trop2 in LSCC development remains
      unclear. In the current study, Trop2 protein expression in fresh LSCC tissue and
      paracancerous tissue was investigated using western blotting. Trop2 in the Hep2
      laryngeal cell line was subsequently suppressed by transfection with small
      interfering RNA (siRNA). The effects of knockdown of Trop2 on cell viability,
      migration, invasiveness and ERK/MAPK pathway activity were investigated in the
      current study. The expression of Trop2 in fresh LSCC tissue was demonstrated to
      be significantly greater than that in paracancerous tissue. Trop2 expression was
      also identified to be required for proliferation, migration and invasiveness of
      Hep2 laryngeal carcinoma cells, as all were blocked by siRNA-mediated Trop2
      inhibition. Notably, the ERK/MAPK signaling pathway and cell cycle factor, cyclin
      D1, were identified to be suppressed following the knockdown of Trop2 in Hep2
      cells. These observations suggest that Trop2 serves an oncogenic role in LSCC and
      has potential as a therapeutic target.

PMID- 25779929
TI  - A case of loose anagen syndrome in an African American girl.
AB  - We present the case of 7-year-old African American girl with loose anagen
      syndrome. Although this is a common cause of hair loss in Caucasian children, and
      there have been reports of cases occurring in dark-skinned children of North
      African and Middle Eastern descent, to our knowledge there have been no cases
      reported in black children of sub-Saharan African ancestry. We present this case
      to broaden the differential diagnosis of hair loss in African Americans. 

PMID- 25779930
TI  - Suppression of adenosine 2a receptor (A2aR)-mediated adenosine signaling improves
      disease phenotypes in a mouse model of amyotrophic lateral sclerosis.
AB  - Amyotrophic lateral sclerosis (ALS) is a rapidly progressing neurodegenerative
      disease in which the majority of upper and lower motor neurons are degenerated.
      Despite intensive efforts to identify drug targets and develop neuroprotective
      strategies, effective therapeutics for ALS remains unavailable. The
      identification and characterization of novel targets and pathways remain crucial
      in the development of ALS therapeutics. Adenosine is a major neuromodulator that
      actively regulates synaptic transmission. Interestingly, adenosine levels are
      significantly elevated in the cerebrospinal fluid (CSF) of progressing human ALS
      patients. In the current study, we showed that adenosine 2a receptor (A2aR), but
      not adenosine 1 receptor (A1R), is highly enriched in spinal (motor) neurons.
      A2aR expression is also selectively increased at the symptomatic onset in the
      spinal cords of SOD1G93A mice and end-stage human ALS spinal cords.
      Interestingly, we found that direct adenosine treatment is sufficient to induce
      embryonic stem cell-derived motor neuron (ESMN) cell death in cultures.
      Subsequent pharmacological inhibition and partial genetic ablation of A2aR
      (A2aR(+/-)) significantly protect ESMN from SOD1G93A(+) astrocyte-induced cell
      death and delay disease progression of SOD1G93A mice. Taken together, our results
      provide compelling novel evidence that A2aR-mediated adenosine signaling
      contributes to the selective spinal motor neuron degeneration observed in the
      SOD1G93A mouse model of ALS. 

PMID- 25779931
TI  - ENU mutagenesis identifies mice modeling Warburg Micro Syndrome with sensory axon
      degeneration caused by a deletion in Rab18.
AB  - Mutations in the gene of RAB18, a member of Ras superfamily of small G-proteins,
      cause Warburg Micro Syndrome (WARBM) which is characterized by defective
      neurodevelopmental and ophthalmological phenotypes. Despite loss of Rab18 had
      been reported to induce disruption of the endoplasmic reticulum structure and
      neuronal cytoskeleton organization, parts of the pathogenic mechanism caused by
      RAB18 mutation remain unclear. From the N-ethyl-N-nitrosourea (ENU)-induced
      mutagenesis library, we identified a mouse line whose Rab18 was knocked out. This
      Rab18(-/-) mouse exhibited stomping gait, smaller testis and eyes, mimicking
      several features of WARBM. Rab18(-/-) mice were obviously less sensitive to pain
      and touch than WT mice. Histological examinations on Rab18(-/-) mice revealed
      progressive axonal degeneration in the optic nerves, dorsal column of the spinal
      cord and sensory roots of the spinal nerves while the motor roots were spared.
      All the behavioral and pathological changes that resulted from abnormalities in
      the sensory axons were prevented by introducing an extra copy of Rab18 transgene
      in Rab18(-/-) mice. Our results reveal that sensory axonal degeneration is the
      primary cause of stomping gait and progressive weakness of the hind limbs in
      Rab18(-/-) mice, and optic nerve degeneration should be the major pathology of
      progressive optic atrophy in children with WARBM. Our results indicate that the
      sensory nervous system is more vulnerable to Rab18 deficiency and WARBM is not
      only a neurodevelopmental but also neurodegenerative disease. 

PMID- 25779932
TI  - Nursing staff induced repositionings and immobile patients' spontaneous movements
      in nursing care.
AB  - The aim of this study was to investigate nursing staff induced repositionings and
      the patients' spontaneous movements during the day and night among older immobile
      patients in nursing care. Furthermore, the aim was to identify factors associated
      with the nursing staff induced repositionings and the patients' spontaneous
      movement frequency. An observational cross-sectional design was used. Spontaneous
      movements among patients (n = 52) were registered continuously using the
      MovinSense monitoring system. The nursing staff documented each time they
      repositioned the patient. Patients spontaneous movements were compared with
      nursing staff induced repositionings. There were large variations in the
      patients' spontaneous repositioning frequency during both days and nights, which
      shows that, although immobilised, some patients frequently reposition themselves.
      Analgesics were positively related to the movement frequency and psycholeptics
      were negatively related. The nursing staff more often repositioned the patients
      who were assessed as high risk than those assessed as low risk, but the patients'
      spontaneous movement frequency was not correlated to the risk score. This may be
      important when planning repositioning schedules. A monitoring system may be
      useful in decision making with regard to planning repositioning and positions
      used in the prevention of pressure ulcers among elderly immobile patients.

PMID- 25779933
TI  - Significant bone microarchitecture impairment in premenopausal women with active
      celiac disease.
AB  - Patients with active celiac disease (CD) are more likely to have osteoporosis and
      increased risk of fractures. High-resolution peripheral quantitative computed
      tomography (HR-pQCT) permits three-dimensional exploration of bone
      microarchitectural characteristics measuring separately cortical and trabecular
      compartments, and giving a more profound insight into bone disease
      pathophysiology and fracture. We aimed to determine the volumetric and
      microarchitectural characteristics of peripheral bones-distal radius and tibia-in
      an adult premenopausal cohort with active CD assessed at diagnosis. We
      prospectively enrolled 31 consecutive premenopausal women with newly diagnosed CD
      (median age 29 years, range: 18-49) and 22 healthy women of similar age (median
      age 30 years, range 21-41) and body mass index. Compared with controls,
      peripheral bones of CD patients were significantly lower in terms of total
      volumetric density mg/cm(3) (mean +/- SD: 274.7 +/- 51.7 vs. 324.7 +/- 45.8, p
      0.0006 at the radius; 264.4 +/- 48.7 vs. 307 +/- 40.7, p 0.002 at the tibia),
      trabecular density mg/cm(3) (118.6 +/- 31.5 vs. 161.9 +/- 33.6, p<0.0001 at the
      radius; 127.9 +/- 28.7 vs. 157.6 +/- 15.6, p < 0.0001 at the tibia); bone
      volume/trabecular volume ratio % (9.9 +/- 2.6 vs. 13.5 +/- 2.8, p<0.0001 at the
      radius; 10.6 +/- 2.4 vs. 13.1 +/- 1.3, p < 0.0001 at the tibia); number of
      trabeculae 1/mm (1.69 +/- 0.27 vs. 1.89 +/- 0.26, p 0.009 at the radius; 1.53 +/-
      0.32 vs. 1.80 +/- 0.26, p 0.002 at the tibia); and trabecular thickness mm (0.058
      +/- 0.010 vs. 0.071 +/- 0.008, p < 0.0001 at the radius with no significant
      difference at the tibia). Cortical density was significantly lower in both
      regions (D comp mg/cm(3) 860 +/- 57.2 vs. 893.9 +/- 43, p 0.02; 902.7 +/- 48.7
      vs. 932.6 +/- 32.6, p 0.01 in radius and tibia respectively). Although cortical
      thickness was lower in CD patients, it failed to show any significant inter-group
      difference (a-8% decay with p 0.11 in both bones). Patients with symptomatic CD
      (n = 22) had a greater bone microarchitectural deficit than those with
      subclinical CD. HR-pQCT was used to successfully identify significant
      deterioration in the microarchitecture of trabecular and cortical compartments of
      peripheral bones. Impairment was characterized by lower trabecular number and
      thickness-which increased trabecular network heterogeneity-and lower cortical
      density and thickness. In the prospective follow-up of this group of patients we
      expect to be able to assess whether bone microarchitecture recovers and to what
      extend after gluten-free diet.

PMID- 25779934
TI  - Age-related differences in factors associated with cervical spine injuries in
      children.
AB  - OBJECTIVES: The Pediatric Emergency Care Applied Research Network (PECARN)
      investigators previously identified risk factors associated with cervical spine
      injuries (CSIs) in children. Anatomic maturation and age-related variation in
      mechanisms of injury suggested the need to explore factors separately for younger
      versus older children. The purpose of this substudy was to investigate CSI risk
      factors in age subgroups within the PECARN study cohort. METHODS: This was an age
      stratified case-control analysis of children younger than 16 years presenting to
      17 PECARN hospitals following blunt trauma between January 1, 2000 and December
      31, 2004. Data were abstracted for children with CSIs and randomly selected CSI
      free children. Age-stratified multivariable logistic regression was performed to
      identify factors associated with CSI within three age groups: younger than 2, 2
      to 7, and 8 to 15 years. Sensitivity and specificity for CSI were estimated for
      both the age-specific and original (altered mental status, focal neurologic
      findings, neck pain, torticollis, substantial torso injury, predisposing
      conditions, diving, and high-risk motor vehicle crash [MVC]) models. RESULTS:
      Among 540 children with CSIs, 27 were younger than 2 years, 140 were 2 to 7
      years, and 373 were 8 to 15 years. Focal neurologic deficits and high-risk MVC
      were associated with CSIs in all age-specific models. Other age-specific factors
      included the following: younger than 2 years, none; 2 to 7 years, altered mental
      status, neck pain, torticollis; and 8 to 15 years, altered mental status, neck
      pain, diving. Age-specific models had comparable sensitivity to the original
      model among the older groups, but had lower sensitivity and higher specificity
      among the youngest children. CONCLUSIONS: While this analysis supports the
      original PECARN model for CSI, there were subtle age variations in factors
      associated with CSIs in children that warrant future investigation.

PMID- 25779935
TI  - New Trends in Food Allergens Detection: Toward Biosensing Strategies.
AB  - Food allergens are a real threat to sensitized individuals. Although food
      labeling is crucial to provide information to consumers with food allergies,
      accidental exposure to allergenic proteins may result from undeclared allergenic
      substances by means of food adulteration, fraud or uncontrolled cross
      contamination. Allergens detection in foodstuffs can be a very hard task, due to
      their presence usually in trace amounts, together with the natural interference
      of the matrix. Methods for allergens analysis can be mainly divided in two large
      groups: the immunological assays and the DNA-based ones. Mass spectrometry has
      also been used as a confirmatory tool. Recently, biosensors appeared as
      innovative, sensitive, selective, environmentally friendly, cheaper and fast
      techniques (especially when automated and/or miniaturized), able to effectively
      replace the classical methodologies. In this review, we present the advances in
      the field of food allergens detection toward the biosensing strategies and
      discuss the challenges and future perspectives of this technology. 

PMID- 25779936
TI  - A novel profibrotic mechanism mediated by TGFbeta-stimulated collagen prolyl
      hydroxylase expression in fibrotic lung mesenchymal cells.
AB  - Idiopathic pulmonary fibrosis is a severe chronic lung disease with a high
      mortality rate. Excessive TGFbeta signalling is recognized as a central player in
      lung fibrosis. However, the related mechanisms remain unclear. Herein we used a
      novel Tbx4 lung enhancer-driven Tet-On transgenic system to inhibit TGFbeta
      signalling in mouse lung-resident mesenchymal cells at different stages of
      bleomycin-induced fibrosis, by conditionally knocking out TGFbeta receptor II or
      expressing a dominant-negative TGFbeta receptor II. Abrogation of mesenchymal
      TGFbeta signalling markedly attenuated bleomycin-induced fibrotic pathology,
      which was independent of altered early inflammation. Furthermore, a novel TGFbeta
      downstream target gene P4HA3 (an alpha-subunit of collagen prolyl hydroxylase)
      was identified, and its expression was significantly increased in fibroblastic
      foci of both bleomycin-induced fibrotic mouse lungs and idiopathic pulmonary
      fibrosis patients' lungs. The relationship between activated TGFbeta signalling,
      up-regulation of P4HA3 and increased hydroxyproline/collagen production was
      further verified in cultured lung fibroblasts. Moreover, inhibition of collagen
      prolyl hydroxylase by pyridine-2,5-dicarboxylate attenuated TGFbeta-stimulated
      collagen production in both cultured fibroblasts and bleomycin-induced mouse lung
      fibrosis. These data indicate that increased expression and activity of collagen
      prolyl hydroxylase is one of the important mechanisms underlying TGFbeta-mediated
      profibrotic effects. Inhibition of collagen prolyl hydroxylase may be a new,
      promising approach for preventing and treating pulmonary fibrosis.

PMID- 25779937
TI  - CSF miR-16 is decreased in major depression patients and its neutralization in
      rats induces depression-like behaviors via a serotonin transmitter system.
AB  - BACKGROUND: Animal and cell line studies demonstrated that miR-16 may be
      associated with major depressive disorder (MDD) via regulation of the expression
      of serotonin transporter (SERT) gene. However, human studies about miR-16 of
      patients with MDD are still lacking. The aim of this study was to investigate the
      possible involvement of miR-16 in the mechanism of MDD in humans. METHODS: Thirty
      six drug-free patients with MDD and 30 healthy controls aged between 18 and 45
      years old were recruited. 24-item Hamilton depression scale test was performed
      for each subject. MiR-16 in cerebrospinal fluid (CSF) and blood, as well as
      serotonin in CSF were assayed by the qRT-PCR or ELISA method. To confirm the role
      of CSF miR-16 in MDD, animal study about intracerebroventricular injection of
      anti-miR-16 was also performed. Depression-like behaviors, CSF miR-16 and
      serotonin, blood miR-16, and raphe SERT protein of rats were also tested.
      RESULTS: CSF miR-16 in MDD patients was significantly lower than that in
      controls. It was negatively correlated with Hamilton scores and positively
      associated with CSF serotonin. However, blood miR-16 was not significantly
      different between two groups and it was not statistically correlated with CSF miR
      16. In animal study, anti-miR-16-treated rats were evaluated to exhibit
      depression-like behaviors, extremely lower CSF miR-16, significantly higher CSF
      serotonin, and obviously higher raphe SERT protein than control rats. LIMITATION:
      We did not detect SERT protein in human brain due to the impossibility of sample
      collection. CONCLUSION: Our study suggested that CSF miR-16 participated in the
      physiopathology of MDD via the modulation of serotonin transmitter system in
      brain.

PMID- 25779938
TI  - Supplementation with vitamin E alone is associated with reduced myocardial
      infarction: a meta-analysis.
AB  - BACKGROUND AND AIMS: Previous meta-analyses of interventional trials with vitamin
      E provided negative results but it remains unclear if this vitamin has some
      influence on cardiovascular events when supplemented alone. The aim of this study
      was to compare the effect of vitamin E alone or in combination with other
      antioxidants on myocardial infarction. METHODS AND RESULTS: Pubmed, ISI Web of
      Science, SCOPUS and Cochrane database were searched without language
      restrictions. We investigated randomized clinical trials studying the effect of
      vitamin E supplementation on myocardial infarction. Sixteen randomized controlled
      trials of vitamin E treatment were analyzed in this meta-analysis. The dose range
      for vitamin E was 33-800IU. Follow-up ranged from 0.5 to 9.4 years. Compared to
      controls, vitamin E given alone significantly decreased myocardial infarction
      (3.0% vs 3.4%) (random effects R.R.: 0.82; 95% C.I., 0.70-0.96; p = 0.01). This
      effect was driven by reduction of fatal myocardial infarction (random effects
      R.R.: 0.84; 95% C.I., 0.73-0.96; p = 0.01). CONCLUSIONS: When supplemented alone,
      vitamin E reduces myocardial infarction in interventional trials while it appears
      ineffective when associated with other antioxidants.

PMID- 25779939
TI  - Fluorescent analysis for bioindication of ozone on unicellular models.
AB  - Unicellular model plant systems (vegetative microspores of horsetail Equisetum
      arvense and pollen of six plant species Corylus avellana, Dolichothele albescens
      Populus balsamifera, Salix caprea, Saintpaulia ionantha, Tulipa hybridum, on
      which autofluorescence and fluorescence after histochemical treatment studied,
      have been represented as bioindicators of ozone. It has found that low doses of
      ozone 0.005 or 0.008 MUl/l did not affect or stimulate the autofluorescence of
      the samples with the ability to germinate in an artificial medium. In higher
      ozone concentrations (0.032 MUl/l) either the decrease in the intensity of the
      emission or changing in the position of the maxima in the fluorescence spectrum
      (new 515-520 nm maximum characteristic for the green-and yellow area has
      appeared) were observed. In dose of 0.2 MUl/l, higher than above the threshold of
      danger to human health, autofluorescence in all samples fell down to up to zero,
      and there was no the ability to germinate. In this case the formation of
      lipofuscin-like compounds fluoresced in blue with maxima from 440 to 485 nm was
      observed. Stress metabolites, known as neurotransmitters biogenic amines, were
      found in treated cells as determined on the characteristic fluorescence at 460
      480 nm in the samples after a specific histochemical reactions for catecholamines
      (with glyoxylic acid) or for histamine (with o-phthalic aldehyde). Increased
      intensity of the emission under the treatment with ozone (total doses from 0.012
      to 0.032 MUl/l) was associated with an increase in the concentrations of
      catecholamines and histamine. The fluorescent analysis on undamaged cells
      possible bioindicators of ozone can be useful in ecomonitoring for earlier
      warning about health hazardous concentrations of this compound in the air. 

PMID- 25779940
TI  - Ruthenium (II) Complexes of Mono-, Di- and Tripodal Polypyridine Ligands:
      Synthesis, Characterization, and Spectroscopic Studies.
AB  - Mono-, di- and tripodal polypyridine ligands 4-(1H-imidazo[4,5
      f][1,10]phenanthroline-2-yl)phenol (L1), 2-(4-(2-((4-(1H-imidazo[4,5
      f][1,10]phenanthroline-2-yl)phenoxy)methyl)benzyloxy)phenyl)-1H-imidazo[4,5
      f][1,10]phenanthroline (L2), 2-(4-(4-((4-(1H-imidazo[4,5-f][1,10]phenanthroline-2
      yl)phenoxy)methyl)benzyl oxy)phenyl)-1H-imidazo[4,5-f][1,10]phenanthroline (L3),
      2-(4-(4,6-bis(4-(1H-imidazo[4,5-f][1,10] phenanthroline-2-yl)phenoxy)-1,3,5
      triazine-2-yloxy)phenyl)-1H-imidazo[4,5-f][1,10]phenanthroline (L4), and their Ru
      (II) complexes have been synthesized and characterized. All the ligands (L1-L4)
      gave the emissions at three shoulder at 278 nm, 315 nm, and 328 nm and the
      complexes (C1-C4) exhibit Ru (II) metal centered emission at 265 nm, 288 nm and
      328 nm in acetonitrile solution at room temperature. Maximum d-pi* transition
      seen at 462 nm for all the complexes. 

PMID- 25779941
TI  - Genomic landscape of human papillomavirus-associated cancers.
AB  - Recent next-generation sequencing studies have generated a comprehensive overview
      of the genomic landscape of human papillomavirus (HPV)-associated cancers. This
      review summarizes these findings to provide insight into the tumor biology of
      these cancers and potential therapeutic opportunities for HPV-driven
      malignancies. In addition to the tumorigenic properties of the HPV oncoproteins,
      integration of HPV DNA into the host genome is suggested to be a driver of the
      neoplastic process. Integration may confer a growth and survival advantage via
      enhanced expression of viral oncoproteins, alteration of critical cellular genes,
      and changes in global promoter methylation and transcription. Alteration of
      cellular genes may lead to loss of function of tumor suppressor genes, enhanced
      oncogene expression, loss of function of DNA repair genes, or other vital
      cellular functions. Recurrent integrations in RAD51B, NR4A2, and TP63, leading to
      aberrant forms of these proteins, are observed in both HPV-positive head and neck
      squamous cell carcinoma (HNSCC) and cervical carcinoma. Additional genomic
      alterations, independent of integration events, include recurrent PIK3CA
      mutations (and aberrations in other members of the PI3K pathway), alterations in
      receptor tyrosine kinases (primarily FGFR2 and FGFR3 in HPV-positive HNSCC, and
      ERBB2 in cervical squamous cell carcinoma), and genes in pathways related to
      squamous cell differentiation and immune responses. A number of the alterations
      identified are potentially targetable, which may lead to advances in the
      treatment of HPV-associated cancers.

PMID- 25779942
TI  - SLFN11 Is a Transcriptional Target of EWS-FLI1 and a Determinant of Drug Response
      in Ewing Sarcoma.
AB  - PURPOSE: SLFN11 was identified as a critical determinant of response to DNA
      targeted therapies by analyzing gene expression and drug sensitivity of NCI-60
      and CCLE datasets. However, how SLFN11 is regulated in cancer cells remained
      unknown. Ewing sarcoma, which is characterized by the chimeric transcription
      factor EWS-FLI1, has notably high SLFN11 expression, leading us to investigate
      whether EWS-FLI1 drives SLFN11 expression and the role of SLFN11 in the drug
      response of Ewing sarcoma cells. EXPERIMENTAL DESIGN: Binding sites of EWS-FLI1
      on the SLFN11 promoter were analyzed by chromatin immunoprecipitation sequencing
      and promoter-luciferase reporter analyses. The relationship between SLFN11 and
      EWS-FLI1 were further examined in EWS-FLI1-knockdown or -overexpressing cells and
      in clinical tumor samples. RESULTS: EWS-FLI1 binds near the transcription start
      site of SLFN11 promoter and acts as a positive regulator of SLFN11 expression in
      Ewing sarcoma cells. EWS-FLI1-mediated SLFN11 expression is responsible for high
      sensitivity of Ewing sarcoma to camptothecin and combinations of PARP inhibitors
      with temozolomide. Importantly, Ewing sarcoma patients with higher SLFN11
      expression showed better tumor-free survival rate. The correlated expression
      between SLFN11 and FLI1 extends to leukemia, pediatric, colon, breast, and
      prostate cancers. In addition, expression of other ETS members correlates with
      SLFN11 in NCI-60 and CCLE datasets, and molecular experiments demonstrate that
      ETS1 acts as a positive regulator for SLFN11 expression in breast cancer cells.
      CONCLUSIONS: Our results imply the emerging relevance of SLFN11 as an ETS
      transcription factor response gene and for therapeutic response to topoisomerase
      I inhibitors and temozolomide-PARP inhibitor combinations in ETS-activated
      cancers.

PMID- 25779943
TI  - Genetics and Prognostication in Splenic Marginal Zone Lymphoma: Revelations from
      Deep Sequencing.
AB  - PURPOSE: Mounting evidence supports the clinical significance of gene mutations
      and immunogenetic features in common mature B-cell malignancies. EXPERIMENTAL
      DESIGN: We undertook a detailed characterization of the genetic background of
      splenic marginal zone lymphoma (SMZL), using targeted resequencing and explored
      potential clinical implications in a multinational cohort of 175 patients with
      SMZL. RESULTS: We identified recurrent mutations in TP53 (16%), KLF2 (12%),
      NOTCH2 (10%), TNFAIP3 (7%), MLL2 (11%), MYD88 (7%), and ARID1A (6%), all genes
      known to be targeted by somatic mutation in SMZL. KLF2 mutations were early,
      clonal events, enriched in patients with del(7q) and IGHV1-2*04 B-cell receptor
      immunoglobulins, and were associated with a short median time to first treatment
      (0.12 vs. 1.11 years; P = 0.01). In multivariate analysis, mutations in NOTCH2
      [HR, 2.12; 95% confidence interval (CI), 1.02-4.4; P = 0.044] and 100% germline
      IGHV gene identity (HR, 2.19; 95% CI, 1.05-4.55; P = 0.036) were independent
      markers of short time to first treatment, whereas TP53 mutations were an
      independent marker of short overall survival (HR, 2.36; 95 % CI, 1.08-5.2; P =
      0.03). CONCLUSIONS: We identify key associations between gene mutations and
      clinical outcome, demonstrating for the first time that NOTCH2 and TP53 gene
      mutations are independent markers of reduced treatment-free and overall survival,
      respectively.

PMID- 25779944
TI  - The MET Inhibitor AZD6094 (Savolitinib, HMPL-504) Induces Regression in Papillary
      Renal Cell Carcinoma Patient-Derived Xenograft Models.
AB  - PURPOSE: Papillary renal cell carcinoma (PRCC) is the second most common cancer
      of the kidney and carries a poor prognosis for patients with nonlocalized
      disease. The HGF receptor MET plays a central role in PRCC and aberrations,
      either through mutation, copy number gain, or trisomy of chromosome 7 occurring
      in the majority of cases. The development of effective therapies in PRCC has been
      hampered in part by a lack of available preclinical models. We determined the
      pharmacodynamic and antitumor response of the selective MET inhibitor AZD6094 in
      two PRCC patient-derived xenograft (PDX) models. EXPERIMENTAL DESIGN: Two PRCC
      PDX models were identified and MET mutation status and copy number determined.
      Pharmacodynamic and antitumor activity of AZD6094 was tested using a dose
      response up to 25 mg/kg daily, representing clinically achievable exposures, and
      compared with the activity of the RCC standard-of-care sunitinib (in RCC43b) or
      the multikinase inhibitor crizotinib (in RCC47). RESULTS: AZD6094 treatment
      resulted in tumor regressions, whereas sunitinib or crizotinib resulted in
      unsustained growth inhibition. Pharmacodynamic analysis of tumors revealed that
      AZD6094 could robustly suppress pMET and the duration of target inhibition was
      dose related. AZD6094 inhibited multiple signaling nodes, including MAPK, PI3K,
      and EGFR. Finally, at doses that induced tumor regression, AZD6094 resulted in a
      dose- and time-dependent induction of cleaved PARP, a marker of cell death.
      CONCLUSIONS: Data presented provide the first report testing therapeutics in
      preclinical in vivo models of PRCC and support the clinical development of
      AZD6094 in this indication.

PMID- 25779946
TI  - PLEKHA5: A Key to Unlock the Blood-Brain Barrier?
AB  - Brain metastases represent a devastating complication of melanoma. Our
      understanding of the mechanisms driving metastasis to the brain is limited.
      PLEKHA5 functions as a regulator of brain metastasis in melanoma, and further
      investigation is warranted to explore the use of PLEKHA5 as a potential
      therapeutic target.

PMID- 25779945
TI  - The Use of Transcriptional Profiling to Improve Personalized Diagnosis and
      Management of Cutaneous T-cell Lymphoma (CTCL).
AB  - PURPOSE: Although many patients with mycosis fungoides presenting with stage I
      disease enjoy an indolent disease course and normal life expectancy, about 15% to
      20% of them progress to higher stages and most ultimately succumb to their
      disease. Currently, it is not possible to predict which patients will progress
      and which patients will have a stable disease. Previously, we conducted
      microarray analyses with RT-PCR validation of gene expression in biopsy specimens
      from 60 patients with stage I-IV cutaneous T-cell lymphoma (CTCL), identified
      three distinct clusters based upon transcription profile, and correlated our
      molecular findings with 6 years of clinical follow-up. EXPERIMENTAL DESIGN: We
      test by RT-PCR within our prediction model the expression of about 240 genes that
      were previously reported to play an important role in CTCL carcinogenesis. We
      further extend the clinical follow-up of our patients to 11 years. We compare the
      expression of selected genes between mycosis fungoides/Sezary syndrome and benign
      inflammatory dermatoses that often mimic this cancer. RESULTS: Our findings
      demonstrate that 52 of the about 240 genes can be classified into cluster 1-3
      expression patterns and such expression is consistent with their suggested
      biologic roles. Moreover, we determined that 17 genes (CCL18, CCL26, FYB, T3JAM,
      MMP12, LEF1, LCK, ITK, GNLY, IL2RA, IL26, IL22, CCR4, GTSF1, SYCP1, STAT5A, and
      TOX) are able to both identify patients who are at risk of progression and also
      distinguish mycosis fungoides/Sezary syndrome from benign mimickers. CONCLUSIONS:
      This study, combined with other gene expression analyses, prepares the foundation
      for the development of personalized molecular approach toward diagnosis and
      treatment of CTCL.

PMID- 25779947
TI  - Monoclonal Antibodies Targeting LecLex-Related Glycans with Potent Antitumor
      Activity.
AB  - PURPOSE: To produce antitumor monoclonal antibodies (mAbs) targeting glycans as
      they are aberrantly expressed in tumors and are coaccessory molecules for key
      survival pathways. EXPERIMENTAL DESIGN: Two mAbs (FG88.2 and FG88.7) recognizing
      novel tumor-associated Lewis (Le) glycans were produced by immunizations with
      plasma membrane lipid extracts of the COLO205 cell line. RESULTS: Glycan array
      analysis showed that both mAbs bound Le(c)Le(x), di-Le(a), and Le(a)Le(x), as
      well as Le(a)-containing glycans. These glycans are expressed on both lipids and
      proteins. Both mAbs showed strong tumor reactivity, binding to 71% (147 of 208)
      of colorectal, 81% (155 of 192) of pancreatic, 54% (52 of 96) of gastric, 23% (62
      of 274) of non-small cell lung, and 31% (66 of 217) of ovarian tumor tissue in
      combination with a restricted normal tissue distribution. In colorectal cancer,
      high FG88 glyco-epitope expression was significantly associated with poor
      survival. The mAbs demonstrated excellent antibody-dependent cellular
      cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC), in addition to
      direct tumor cell killing via a caspase-independent mechanism. Scanning electron
      microscopy revealed antibody-induced pore formation. In addition, the mAbs
      internalized, colocalized with lysosomes, and delivered saporin that killed cells
      with subnanomolar potency. In vivo, the mAbs demonstrated potent antitumor
      efficacy in a metastatic colorectal tumor model, leading to significant long-term
      survival. CONCLUSIONS: The mAbs direct and immune-assisted tumor cell killing,
      pan-tumor reactivity, and potent in vivo antitumor efficacy indicate their
      potential as therapeutic agents for the treatment of multiple solid tumors. In
      addition, internalization of saporin conjugates and associated tumor cell killing
      suggests their potential as antibody drug carriers.

PMID- 25779948
TI  - Significance of Circulating Tumor Cells in Metastatic Triple-Negative Breast
      Cancer Patients within a Randomized, Phase II Trial: TBCRC 019.
AB  - PURPOSE: Circulating tumor cells (CTC) are prognostic in metastatic breast cancer
      (MBC). We tested whether EpCAM-based capture system (CellSearch) is effective in
      patients with triple-negative (TN) MBC, and whether CTC apoptosis and clustering
      enhances the prognostic role of CTC. EXPERIMENTAL DESIGN: CTC enumeration and
      apoptosis were determined using the CXC CellSearch kit at baseline and days 15
      and 29 in blood drawn from TN MBC patients who participated in a prospective
      randomized phase II trial of nanoparticle albumin-bound paclitaxel (nab
      paclitaxel) with or without tigatuzumab. Association between levels of CTC and
      patient outcomes was assessed using logistic regression, Kaplan-Meier curves, and
      Cox proportional hazards modeling. RESULTS: Nineteen of 52 (36.5%), 14 of 52
      (26.9%), and 13 of 49 (26.5%) patients who were evaluable had elevated CTC (>=5
      CTC/7.5 mL whole blood) at baseline and at days 15 and 29, respectively. Patients
      with elevated versus not elevated CTC at each time point had worse progression
      free survival (PFS; P = 0.005, 0.0003, 0.0002, respectively). The odds of
      clinical benefit response for those who had elevated versus low CTC at baseline
      and days 15 and 29 were 0.25 (95% CI: 0.08-0.84; P = 0.024), 0.19 (95% CI: 0.05
      0.17; P = 0.014), and 0.06 (95% CI: 0.01-0.33; P = 0.001), respectively. There
      was no apparent prognostic effect comparing CTC apoptosis versus non-apoptosis.
      Presence of CTC cluster at day 15 and day 29 was associated with shorter PFS.
      CONCLUSIONS: CTC were detected using CellSearch assay in approximately one-third
      of TN MBC patients. Elevated CTC at baseline and days 15 and 29 were prognostic,
      and reductions in CTC levels reflected response.

PMID- 25779949
TI  - A New and Validated Clinical Prognostic Model (EPI) for Enteropathy-Associated T
      cell Lymphoma.
AB  - PURPOSE: Enteropathy-associated T-cell lymphoma (EATL) is a rare intestinal non
      Hodgkin lymphoma with a poor, though variable prognosis. The International
      Prognostic Index (IPI) and the prognostic index for peripheral T-cell lymphoma
      (PIT) have limited predictive value for outcome of EATL. The purpose of this
      study was to develop and validate a prognostic model for EATL, which can identify
      high-risk patients who need more aggressive therapy. EXPERIMENTAL DESIGN: This
      retrospective multicenter study was based on 92 patients and included 45 patients
      diagnosed with EATL between 1999 and 2009 from the Netherlands and 47 patients
      from England and Scotland, diagnosed with EATL between 1994 and 1998. A new EATL
      prognostic index (EPI) was constructed using the RPART (recursive partitioning
      and regression trees) procedure. Validation was performed applying the bootstrap
      method. RESULTS: Three risk groups were distinguished (P < 0.0001): a high-risk
      group, characterized by the presence of B-symptoms [median overall survival (OS)
      of 2 months]; an intermediate-risk group, comprising patients without B-symptoms
      and an IPI score >= 2 (7 months); and a low-risk group, representing patients
      without B-symptoms and an IPI score of 0 to 1 (34 months). Internal validation
      showed stability of statistical significance and prognostic discrimination. In
      contrast with the IPI and PIT, the EPI better classified patients in risk groups
      according to their clinical outcome. CONCLUSIONS: Our new, validated, prognostic
      model EPI accurately predicts survival outcome in EATL and may be used for
      patient selection for new therapeutic strategies and evaluation of clinical
      trials.

PMID- 25779950
TI  - Targeting IL11 Receptor in Leukemia and Lymphoma: A Functional Ligand-Directed
      Study and Hematopathology Analysis of Patient-Derived Specimens.
AB  - PURPOSE: The IL11 receptor (IL11R) is an established molecular target in primary
      tumors of bone, such as osteosarcoma, and in secondary bone metastases from solid
      tumors, such as prostate cancer. However, its potential role in management of
      hematopoietic malignancies has not yet been determined. Here, we evaluated the
      IL11R as a candidate therapeutic target in human leukemia and lymphoma.
      EXPERIMENTAL DESIGN AND RESULTS: First, we show that the IL11R protein is
      expressed in a variety of human leukemia- and lymphoma-derived cell lines and in
      a large panel of bone marrow samples from leukemia and lymphoma patients, whereas
      expression is absent from nonmalignant control bone marrow. Moreover, a targeted
      peptidomimetic prototype (termed BMTP-11), specifically bound to leukemia and
      lymphoma cell membranes, induced ligand-receptor internalization mediated by the
      IL11R, and resulted in a specific dose-dependent cell death induction in these
      cells. Finally, a pilot drug lead-optimization program yielded a new
      myristoylated BMTP-11 analogue with an apparent improved antileukemia cell
      profile. CONCLUSIONS: These results indicate (i) that the IL11R is a suitable
      cell surface target for ligand-directed applications in human leukemia and
      lymphoma and (ii) that BMTP-11 and its derivatives have translational potential
      against this group of malignant diseases.

PMID- 25779951
TI  - Immune Recovery after Allogeneic Hematopoietic Stem Cell Transplantation
      Following Flu-TBI versus TLI-ATG Conditioning.
AB  - PURPOSE: A conditioning regimen for allogeneic hematopoietic cell transplantation
      (HCT) combining total lymphoid irradiation (TLI) plus anti-thymocyte globulin
      (ATG) has been developed to induce graft-versus-tumor effects without graft
      versus-host disease (GVHD). EXPERIMENTAL DESIGN: We compared immune recovery in
      53 patients included in a phase II randomized study comparing nonmyeloablative
      HCT following either fludarabine plus 2 Gy total body irradiation (TBI arm, n =
      28) or 8 Gy TLI plus ATG (TLI arm, n = 25). RESULTS: In comparison with TBI
      patients, TLI patients had a similarly low 6-month incidence of grade II-IV acute
      GVHD, a lower incidence of moderate/severe chronic GVHD (P = 0.02), a higher
      incidence of CMV reactivation (P < 0.001), and a higher incidence of relapse (P =
      0.01). While recovery of total CD8(+) T cells was similar in the two groups, with
      median CD8(+) T-cell counts reaching the normal values 40 to 60 days after allo
      HCT, TLI patients had lower percentages of naive CD8 T cells. Median CD4(+) T
      cell counts did not reach the lower limit of normal values the first year after
      allo-HCT in the two groups. Furthermore, CD4(+) T-cell counts were significantly
      lower in TLI than in TBI patients the first 6 months after transplantation.
      Interestingly, while median absolute regulatory T-cell (Treg) counts were
      comparable in TBI and TLI patients, Treg/naive CD4(+) T-cell ratios were
      significantly higher in TLI than in TBI patients the 2 first years after
      transplantation. CONCLUSIONS: Immune recovery differs substantially between these
      two conditioning regimens, possibly explaining the different clinical outcomes
      observed (NCT00603954).

PMID- 25779952
TI  - SIRT1/PGC1alpha-Dependent Increase in Oxidative Phosphorylation Supports
      Chemotherapy Resistance of Colon Cancer.
AB  - PURPOSE: Chemotherapy treatment of metastatic colon cancer ultimately fails due
      to development of drug resistance. Identification of chemotherapy-induced changes
      in tumor biology may provide insight into drug resistance mechanisms.
      EXPERIMENTAL DESIGN: We studied gene expression differences between groups of
      liver metastases that were exposed to preoperative chemotherapy or not. Multiple
      patient-derived colonosphere cultures were used to assess how chemotherapy alters
      energy metabolism by measuring mitochondrial biomass, oxygen consumption, and
      lactate production. Genetically manipulated colonosphere-initiated tumors were
      used to assess how altered energy metabolism affects chemotherapy efficacy.
      RESULTS: Gene ontology and pathway enrichment analysis revealed significant
      upregulation of genes involved in oxidative phosphorylation (OXPHOS) and
      mitochondrial biogenesis in metastases that were exposed to chemotherapy. This
      suggested chemotherapy induces a shift in tumor metabolism from glycolysis
      towards OXPHOS. Indeed, chemotreatment of patient-derived colonosphere cultures
      resulted in an increase of mitochondrial biomass, increased expression of
      respiratory chain enzymes, and higher rates of oxygen consumption. This was
      mediated by the histone deacetylase sirtuin-1 (SIRT1) and its substrate, the
      transcriptional coactivator PGC1alpha. Knockdown of SIRT1 or PGC1alpha prevented
      chemotherapy-induced OXPHOS and significantly sensitized patient-derived
      colonospheres as well as tumor xenografts to chemotherapy. CONCLUSIONS:
      Chemotherapy of colorectal tumors induces a SIRT1/PGC1alpha-dependent increase in
      OXPHOS that promotes tumor survival during treatment. This phenomenon is also
      observed in chemotherapy-exposed resected liver metastases, strongly suggesting
      that chemotherapy induces long-lasting changes in tumor metabolism that
      potentially interfere with drug efficacy. In conclusion, we propose a novel
      mechanism of chemotherapy resistance that may be clinically relevant and
      therapeutically exploitable.

PMID- 25779954
TI  - Optical Coherence Tomography Findings After Scoring Balloon Dilatation.

PMID- 25779953
TI  - TBCRC 019: A Phase II Trial of Nanoparticle Albumin-Bound Paclitaxel with or
      without the Anti-Death Receptor 5 Monoclonal Antibody Tigatuzumab in Patients
      with Triple-Negative Breast Cancer.
AB  - PURPOSE: Tigatuzumab (TIG), an agonistic anti-DR5 antibody, triggers apoptosis in
      DR5(+) human tumor cells without crosslinking. TIG has strong in vitro/in vivo
      activity against basal-like breast cancer cells enhanced by chemotherapy agents.
      This study evaluates activity of TIG and chemotherapy in patients with metastatic
      triple-negative breast cancer (TNBC). EXPERIMENTAL DESIGN: Randomized 2:1 phase
      II trial of albumin-bound paclitaxel (nab-PAC) +/- TIG in patients with TNBC
      stratified by prior chemotherapy. Patients received nab-PAC weekly * 3 +/- TIG
      every other week, every 28 days. Primary objective was within-arm objective
      response rate (ORR). Secondary objectives were safety, progression-free survival
      (PFS), clinical benefit, and TIG immunogenicity. Metastatic research biopsies
      were required. RESULTS: Among 64 patients (60 treated; TIG/nab-PAC n = 39 and nab
      PAC n = 21), there were 3 complete remissions (CR), 8 partial remissions (PR; 1
      almost CR), 11 stable diseases (SD), and 17 progressive diseases (PD) in the
      TIG/nab-PAC arm (ORR, 28%), and no CRs, 8 PRs, 4 SDs, and 9 PDs in the nab-PAC
      arm (ORR, 38%). There was a numerical increase in CRs and several patients had
      prolonged PFS (1,025+, 781, 672, 460, 334) in the TIG/nab-PAC arm. Grade 3
      toxicities were 28% and 29%, respectively, with no grade 4-5. Exploratory
      analysis suggests an association of ROCK1 gene pathway activation with efficacy
      in the TIG/nab-PAC arm. CONCLUSIONS: ORR and PFS were similar in both.
      Preclinical activity of TIG in basal-like breast cancer and prolonged PFS in few
      patients in the combination arm support further investigation of anti-DR5 agents.
      ROCK pathway activation merits further evaluation.

PMID- 25779955
TI  - Coronary Thromboembolism During Transcatheter Aortic Valve Replacement.

PMID- 25779956
TI  - The ratios of 2nd to 4th digit may be a predictor of schizophrenia in male
      patients.
AB  - The production of androgens (mostly testosterone) during the early fetal stage is
      essential for the differentiation of the male brain. Some authors have suggested
      a relationship between androgen exposure during the prenatal period and
      schizophrenia. These two separate relationships suggest that digit length ratios
      are associated with schizophrenia in males. The study was performed in a
      university hospital between October 2012 and May 2013. One hundred and three male
      patients diagnosed with schizophrenia according to DSM-IV using SCID-I, and 100
      matched healthy males, were admitted to the study. Scale for the Assessment of
      Positive Symptoms (SAPS), Scale for the Assessment of Negative Symptoms (SANS)
      and Brief Psychiatric Rating Scale (BPRS) were used to assess schizophrenia
      symptoms. The second digit (2D) and fourth digit (4D) asymmetry index (AI), and
      the right- and left-hand 2D:4D ratios were calculated. All parametric data in the
      groups were compared using an independent t-test. The predictive power of the AI
      was estimated by receiver operating characteristics analysis. The 2D:4D AI was
      statistically significantly lower in the patient group than the healthy control
      comparison group. There were significant differences between the schizophrenia
      and the control groups in respect of left 2D:4D and right 2D:4D. There was no
      correlation between AI, left, or right 2D:4D, BPRS, or SAPS in the schizophrenia
      group. However, there was a negative correlation between left 2nd digit (L2D):4D
      and the SANS score. Our findings support the view that the 2D:4D AI can be used
      as a moderate indicator of schizophrenia. Even more simply, the right or left
      2D:4D can be used as an indicator. L2D:4D could indicate the severity of negative
      symptoms.

PMID- 25779957
TI  - Disparities in health status between rural and urban adult males in Lower
      Silesia, Poland.
AB  - Among the factors responsible for disparities in health status is place of
      residence. The aim of the study was to analyze differences in health status in
      4142 adult males from villages and cities in Poland. Eleven biological parameters
      were used to assess the biological age. Among the better educated subjects, nine
      out of the eleven parameters were significantly worse in the rural subjects than
      in their urban counterparts. BMI, percent body fat, white blood cell count and
      blood glucose were higher, whereas respiratory and cardiovascular efficiency were
      lower. Only visual acuity was better in the rural subjects. For the poorly
      educated men, the pattern was generally similar, although the differences between
      the rural and urban subjects were smaller. 

PMID- 25779959
TI  - [Methodological reflections applied to clinical case of a caesarean section
      performed on a pregnant woman with pre-eclampsia].

PMID- 25779960
TI  - [Silence pact from the perspective of caretakers of palliative care patients].
AB  - OBJECTIVES: To determine why terminally-ill patients, family caregivers and
      health care providers make a pact of silence about the terminal status of the
      patient, and to identify the attitudes, experiences and opinions of family
      caregivers concerning the conspiracy of silence in palliative care. METHODS: A
      qualitative phenomenological study based on an interpretive analysis, conducted
      in Primary Health Care, Seville, Spain. Study dimensions: knowledge of the
      diagnosis and prognosis of the condition; disclosure of information; reaction to
      information received, feelings and approach to death; information disclosed to
      the patient and reasons behind partial disclosure; communication between
      patients, families, and health care providers. STUDY POPULATION: Family
      caregivers of patients on palliative care suspicious about a pact of silence.
      RESULTS: Family caregivers hamper professional-patient communication; use of
      deceit to conceal the truth; suspicion that the patient knows the truth; the
      clinician conceals the truth; paternalist attitudes; feelings of sadness, grief,
      resignation, acceptance of the disease. CONCLUSIONS: The pact of silence has
      negative effects on coping with death, quality of life in the last days of life,
      and mourning. Communication between patients, health care providers, and families
      should be improved to prevent the pact of silence, and help patients cope with
      death.

PMID- 25779961
TI  - [Self-efficacy and self management of healthy habits in fibromyalgia].
AB  - Fibromyalgia is a disorder characterized by general chronic pain, together with
      other symptoms such as fatigue, sleep disorders, anxiety and depression. AIM: To
      analyze, in FM patients, the effects of a multi-component intervention program
      (nursing+cognitive-behavioural therapy, focused on improving resting habits,
      physical exercise, and family relationships, working simultaneously on
      empowerment and patient self-efficacy. METHOD: A quasi-experimental design was
      used following-up 5 women diagnosed with fibromyalgia. An analysis was performed
      on their daily habits, self-efficacy for chronic pain, pain perception,
      functional limitation, and affect. The intervention was composed by 8 group
      sessions: Six of them aimed at health education and self-management of healthy
      habits (nursing), and two sessions dedicated to increasing self-efficacy
      (cognitive-behavioural therapy). Follow-up consisted of five individual sessions
      (nursing) so as to consolidate the newly acquired habits, maintain self
      management and self-efficacy based on observing compliance. RESULTS:
      Statistically significant improvements were observed (pre-, pos-) in habit
      modification and in self-efficacy, as well as for positive and negative affect.
      Also, statistically significant differences were found pre-follow up for
      functional limitation. CONCLUSIONS: The role of nursing has to be considered
      within multi-component programs, in particular during follow-up, for changing
      habits and for self-efficacy, in response to some of the current limitations of
      interventions with these patients.

PMID- 25779962
TI  - An unusual cause of acute abdominal pain: mesenteric panniculitis.

PMID- 25779963
TI  - Dysregulation of parkin in the substantia nigra of db/db and high-fat diet mice.
AB  - Parkinson's disease (PD) is characterized by selective loss of dopaminergic
      neurons in the substantia nigra (SN). Epidemiological evidence has suggested a
      link between type 2 diabetes and PD, although the mechanisms remain largely
      unknown. We applied LC-MS/MS-based pattern analysis to investigate altered
      proteomes in the SN of db/db mice (db-SN) and high-fat diet mice (HFD-SN),
      revealing that the level of mitochondrial proteins has changed in the SN of
      diabetic mice compared to that of control mice. Since mitochondrial proteins were
      robustly altered in db-SN and HFD-SN, we performed immunoblot analysis to monitor
      the level of parkin, PINK1 (phosphatase and tensin homolog-induced putative
      kinase 1) and DJ-1 that were directly involved in mitochondrial dynamics. As a
      result, PINK1 and DJ-1 level was unchanged, whereas a significant loss of parkin
      was found in db-SN and HFD-SN, leading to the accumulation of parkin-interacting
      substrate (PARIS) and the reduction of peroxisome proliferator-activated receptor
      gamma coactivator 1-alpha (PGC-1alpha). Interestingly, these alterations were
      reversed by the administration of metformin, one of most frequently prescribed
      anti-hyperglycemic agents. The slight loss of dopaminergic neurons was found in
      chronic HFD-SN that was restored by metformin. Taken together, our data suggest
      that the dysregulation of Parkin-PARIS-PGC-1alpha pathway by metabolic
      malregulation may contribute to the pathogenesis of PD and metformin might exert
      a neuroprotective effect on PD via the restoration of parkin.

PMID- 25779964
TI  - Forebrain neuronal specific ablation of p53 gene provides protection in a
      cortical ischemic stroke model.
AB  - Cerebral ischemic injury involves death of multiple cell types at the ischemic
      sites. As a key regulator of cell death, the p53 gene has been implicated in the
      regulation of cell loss in stroke. Less focal damage is found in stroke animals
      pre-treated with a p53 inhibitor or in traditional p53 knockout (ko) mice.
      However, whether the p53 gene plays a direct role in regulating neuronal cell
      death is unknown. In this study, in contrast to the global inhibition of p53
      function by pharmacological inhibitors and in traditional p53 ko mice, we
      utilized a neuronal specific conditional ko mouse line (CamcreTRP53(loxP/loxP))
      to achieve forebrain neuronal specific deletion of p53 and examined the role of
      the p53 gene in ischemia-induced cell death in neurons. Expression of p53 after
      stroke is examined using the immunohistochemical method and the outcome of stroke
      is examined by analysis of infarction size and behavioral deficits caused by
      stroke. Our data showed that p53 expression is upregulated in the ischemic region
      in neuronal cells in wildtype (wt) mice but not in CamcreTRP53(loxP/loxP) ko
      mice. Deletion of the p53 gene in forebrain neurons results in a decreased
      infarction area in ko mice. Locomotor behavior, measured in automated activity
      chambers, showed that CamcreTRP53(loxP/loxP) ko mice have less locomotor deficits
      compared to wt mice after middle cerebral artery occlusion (MCAo). We conclude
      that manipulation of p53 expression in neurons may lead to unique therapeutic
      development in stroke. 

PMID- 25779965
TI  - Galangin-induced down-regulation of BACE1 by epigenetic mechanisms in SH-SY5Y
      cells.
AB  - Alzheimer's disease (AD), the most common cause of dementia in aging people, is
      found to have a critical link with the deposition of beta-amyloid (Abeta) in the
      brain. The inhibition of beta-site amyloid precursor protein-cleaving enzyme 1
      (BACE1), a key enzyme for Abeta production, is a promising target for AD therapy.
      In pursuit to find a potent inhibitor of BACE1, we identified galangin, a natural
      flavonoid, had a significant lowering effect on Abeta levels. Furthermore, a
      dramatic reduction of BACE1 at mRNA and protein levels was observed after
      galangin treatment. We further investigated whether epigenetic mechanisms, such
      as histone acetylation and DNA methylation, were involved in galangin-induced
      transcriptional regulation of BACE1. Our data show that galangin induces a
      decrease of acetylated H3 in the BACE1 promoter regions through the up-regulation
      of endogenous HDAC1-mediated deacetylation, which is independent of DNA
      methylation status. The above findings suggest a novel mechanism for polyphenols'
      neuroprotective effect in neurodegeneration and galangin as a potential drug
      candidate for AD therapy.

PMID- 25779966
TI  - Prenatal maternal immune activation increases anxiety- and depressive-like
      behaviors in offspring with experimental autoimmune encephalomyelitis.
AB  - Multiple sclerosis (MS) is thought to result from a combination of genetics and
      environmental factors. Several lines of evidence indicate that significant
      prevalence of anxiety and depression-related disorders in MS patients can
      influence the progression of the disease. Although we and others have already
      reported the consequences of prenatal maternal immune activation on anxiety and
      depression, less is known about the interplay between maternal inflammation, MS
      and gender. We here investigated the effects of maternal immune activation with
      Poly I:C during mid-gestation on the progression of clinical symptoms of
      experimental autoimmune encephalomyelitis (EAE; a mouse model of MS), and then
      anxiety- and depressive-like behaviors in non-EAE and EAE-induced offspring were
      evaluated. Stress-induced corticosterone and tumor necrosis factor-alpha (TNF
      alpha) levels in EAE-induced offspring were also measured. Maternal immune
      activation increased anxiety and depression in male offspring, but not in
      females. This immune challenge also resulted in an earlier onset of the EAE
      clinical signs in male offspring and enhanced the severity of the disease in both
      male and female offspring. Interestingly, the severity of the disease was
      associated with increased anxiety/depressive-like behaviors and elevated
      corticosterone or TNF-alpha levels in both sexes. Overall, these data suggest
      that maternal immune activation with Poly I:C during mid-pregnancy increases
      anxiety- and depressive-like behaviors, and the clinical symptoms of EAE in a sex
      dependent manner in non-EAE or EAE-induced offspring. Finally, the progression of
      EAE in offspring seems to be linked to maternal immune activation-induced
      dysregulation in neuro-immune-endocrine system.

PMID- 25779967
TI  - Circadian rhythm disruption in a mouse model of Rett syndrome circadian
      disruption in RTT.
AB  - Disturbances in the sleep/wake cycle are prevalent in patients with Rett syndrome
      (RTT). We sought to determine whether the circadian system is disrupted in a RTT
      model, Mecp2(-/y) mice. We found that MeCP2 mutants showed decreased strength and
      precision of daily rhythms of activity coupled with extremely fragmented sleep.
      The central circadian clock (suprachiasmatic nucleus) exhibited significant
      reduction in the number of neurons expressing vasoactive intestinal peptide (VIP)
      as well as compromised spontaneous neural activity. The molecular clockwork was
      disrupted both centrally in the SCN and in peripheral organs, indicating a
      general disorganization of the circadian system. Disruption of the molecular
      clockwork was observed in fibroblasts of RTT patients. Finally, MeCP2 mutant mice
      were vulnerable to circadian disruption as chronic jet lag accelerated mortality.
      Our finds suggest an integral role of MeCP2 in the circadian timing system and
      provides a possible mechanistic explanation for the sleep/wake distrubances
      observed in RTT patients. The work raises the possibility that RTT patients may
      benefit from a temporally structured environment. 

PMID- 25779969
TI  - Dual-pharmacophore DNA-encoded chemical libraries.
AB  - In contrast to single-pharmacophore DNA-encoded libraries, where only one
      chemical moiety is linked to DNA, dual-pharmacophore DNA-encoded chemical
      libraries feature the display of two independent small-molecules in close
      proximity. This, in principle, allows to explore adjacent epitopes on a
      pharmaceutical target of choice and hence the discovery of simultaneously binding
      pairs of fragments, by virtue of the chelate effect. 

PMID- 25779968
TI  - A cell-penetrating ester of the neural metabolite lanthionine ketimine stimulates
      autophagy through the mTORC1 pathway: Evidence for a mechanism of action with
      pharmacological implications for neurodegenerative pathologies.
AB  - Autophagy is a fundamental cellular recycling process vulnerable to compromise in
      neurodegeneration. We now report that a cell-penetrating neurotrophic and
      neuroprotective derivative of the central nervous system (CNS) metabolite,
      lanthionine ketimine (LK), stimulates autophagy in RG2 glioma and SH-SY5Y
      neuroblastoma cells at concentrations within or below pharmacological levels
      reported in previous mouse studies. Autophagy stimulation was evidenced by
      increased lipidation of microtubule-associated protein 1 light chain 3 (LC3) both
      in the absence and presence of bafilomycin-A1 which discriminates between effects
      on autophagic flux versus blockage of autophagy clearance. LKE treatment caused
      changes in protein level or phosphorylation state of multiple autophagy pathway
      proteins including mTOR; p70S6 kinase; unc-51-like-kinase-1 (ULK1); beclin-1 and
      LC3 in a manner essentially identical to effects observed after rapamycin
      treatment. The LKE site of action was near mTOR because neither LKE nor the mTOR
      inhibitor rapamycin affected tuberous sclerosis complex (TSC) phosphorylation
      status upstream from mTOR. Confocal immunofluorescence imaging revealed that LKE
      specifically decreased mTOR (but not TSC2) colocalization with LAMP2(+) lysosomes
      in RG2 cells, a necessary event for mTORC1-mediated autophagy suppression,
      whereas rapamycin had no effect. Suppression of the LK-binding adaptor protein
      CRMP2 (collapsin response mediator protein-2) by means of shRNA resulted in
      diminished autophagy flux, suggesting that the LKE action on mTOR localization
      may occur through a novel mechanism involving CRMP2-mediated intracellular
      trafficking. These findings clarify the mechanism-of-action for LKE in
      preclinical models of CNS disease, while suggesting possible roles for natural
      lanthionine metabolites in regulating CNS autophagy. 

PMID- 25779971
TI  - A review of olanzapine as an antiemetic in chemotherapy-induced nausea and
      vomiting and in palliative care patients.
AB  - Olanzapine is an atypical antipsychotic agent that blocks multiple neuronal
      receptors involved in the nausea and vomiting pathways. It has therefore been
      studied for the prevention and treatment of chemotherapy-induced emesis and in
      patients in palliative care presenting nausea and vomiting refractory to standard
      antiemetics. Some studies have shown that olanzapine was not inferior to
      aprepitant in the prophylaxis of highly and moderately emetogenic chemotherapy
      and that it increased the rate of complete response when added to a combination
      of a 5-HT3 antagonist, aprepitant and dexamethasone. These studies present so
      many shortcomings, however, that they do not permit us to draw any firm
      conclusions. Oral olanzapine showed superior antiemetic efficacy to
      metoclopramide as rescue treatment to control breakthrough emesis induced by
      chemotherapy. However, an oral formulation is not appropriate because in patients
      with vomiting or severe nausea the mere ingestion of an oral drug could induce
      emesis. Finally, in palliative care olanzapine could control or reduce the
      intensity of nausea and vomiting refractory to standard antiemetics. 

PMID- 25779972
TI  - Phylogeography of the endangered Lesser Antillean iguana, Iguana delicatissima: a
      recent diaspora in an archipelago known for ancient herpetological endemism.
AB  - Iguana delicatissima is an endangered endemic of the Lesser Antilles in the
      Caribbean. Phylogeographic analyses for many terrestrial vertebrate species in
      the Caribbean, particularly lizards, suggest ancient divergence times. Often, the
      closest relatives of species are found on the same island, indicating that
      colonization rates are so low that speciation on islands is often more likely to
      generate biodiversity than subsequent colonization events. Mitochondrial sequence
      analysis of the region spanning ND4 was performed on I. delicatissima individuals
      from islands across the species' range to estimate genetic divergence among
      geographically isolated populations. Five unique haplotypes were recovered from
      46 individuals. The majority of animals carry a single common haplotype. Two of
      the haplotypes were only present in individuals classified as hybrids from Iles
      des Saintes. The final 2 haplotypes, single nucleotide substitutions, were
      present in animals from Ilet Chancel of Martinique and Saint Barthelemy,
      respectively. Despite the great distances between islands and habitat
      heterogeneity within islands, this species is characterized by low haplotype
      diversity. The low mtDNA variation of I. delicatissima suggests a single
      colonization coupled with rapid range expansion, potentially hastened by human
      mediated dispersal. 

PMID- 25779970
TI  - Gene-centric approach identifies new and known loci for FVIII activity and VWF
      antigen levels in European Americans and African Americans.
AB  - Coagulation factor VIII and von Willebrand factor (VWF) are key proteins in
      procoagulant activation. Higher FVIII coagulant activity (FVIII :C) and VWF
      antigen (VWF :Ag) are risk factors for cardiovascular disease and venous
      thromboembolism. Beyond associations with ABO blood group, genetic determinants
      of FVIII and VWF are not well understood, especially in non European-American
      populations. We performed a genetic association study of FVIII :C and VWF:Ag that
      assessed 50,000 gene-centric single nucleotide polymorphisms (SNPs) in 18,556
      European Americans (EAs) and 5,047 African Americans (AAs) from five population
      based cohorts. Previously unreported associations for FVIII :C were identified in
      both AAs and EAs with KNG1 (most significantly associated SNP rs710446,
      Ile581Thr, Ile581Thr, P = 5.10 * 10(-7) in EAs and P = 3.88 * 10(-3) in AAs) and
      VWF rs7962217 (Gly2705Arg,P = 6.30 * 10(-9) in EAs and P = 2.98 * 10(-2) in AAs.
      Significant associations for FVIII :C were also observed with F8/TMLHE region SNP
      rs12557310 in EAs (P = 8.02 * 10(-10) ), with VWF rs1800380 in AAs (P = 5.62 *
      10(-11) ), and with MAT1A rs2236568 in AAs (P51.69 * 10(-6) ). We replicated
      previously reported associations of FVIII :C and VWF :Ag with the ABO blood
      group, VWF rs1063856(Thr789Ala), rs216321 (Ala852Gln), and VWF rs2229446
      (Arg2185Gln). Findings from this study expand our understanding of genetic
      influences for FVIII :C and VWF :Ag in both EAs and AAs.

PMID- 25779973
TI  - Prey or parasite? The first observations of live Euglenida in the intestine of
      Gastrotricha.
AB  - Euglenida are an important element in almost all aquatic ecosystems. They are
      known to parasitize animals such as copepods and flatworms, but have never been
      found in any other microscopic group. Gastrotrichs, a phylum of small
      microinvertebrates, are a constant and important element of marine and freshwater
      ecosystems. During our observation, 72 live gastrotrich specimens were collected
      from Europe (Poland, Germany) and South America (Brazil) containing active
      Euglenida of the genus Heteronema. Euglenida were found in the intestine of
      10.4%, 52.6% and 1% of gastrotrichs, respectively. Taking into consideration the
      existing parasitism in euglenoids, it may be hypothesized that they either
      constitute fortuitous feed in the gastrotrich intestine or they are parasites or
      commensals. These observations suggest a new, so far unknown type of interaction
      between Gastrotricha and protists. 

PMID- 25779974
TI  - Improved sensitization efficiency in Er(3+) ions and SnO2 nanocrystals co-doped
      silica thin films.
AB  - Er(3+) ions and SnO2 nanocrystals co-doped silica thin films are prepared by an
      improved sol-gel spin-coating method. With increase in annealing temperature, the
      related 1.54 MUm characteristic emission intensity from Er(3+) ions is obviously
      enhanced by more than two orders of magnitude via SnO2 nanocrystals size control
      to boost the sensitization efficiency. Quantitative studies of steady-state
      spectroscopic data and fluorescence decay curves demonstrate that the related
      sensitization efficiency via size-tunable nanocrystals is increased from 0.14% to
      1.3%. This improved sensitization efficiency is achieved by doping some of the
      Er(3+) ions into the SnO2 inner sites at a high annealing temperature, as
      revealed by high-resolution TEM, X-ray diffraction patterns and elemental mapping
      technique. Different sensitization mechanisms are also discussed separately
      according to the selective photoluminescence excitation measurements. All these
      results have not only explained the greatly improved sensitization efficiency
      resulting from SnO2 nanocrystals but also indicated that the development of
      Er(3+) ions and SnO2 nanocrystals co-doped silica thin films could result in
      promising high-performance near-infrared luminous materials using broadband UV
      pumping. 

PMID- 25779976
TI  - Predicting risk for childhood asthma by pre-pregnancy, perinatal, and postnatal
      factors.
AB  - BACKGROUND: Symptoms of atopic disease start early in human life. Predicting risk
      for childhood asthma by early-life exposure would contribute to disease
      prevention. A birth cohort study was conducted to investigate early-life risk
      factors for childhood asthma and to develop a predictive model for the
      development of asthma. METHODS: National representative samples of newborn babies
      were obtained by multistage stratified systematic sampling from the 2005 Taiwan
      Birth Registry. Information on potential risk factors and children's health was
      collected by home interview when babies were 6 months old and 5 yr old,
      respectively. Backward stepwise regression analysis was used to identify the risk
      factors of childhood asthma for predictive models that were used to calculate the
      probability of childhood asthma. RESULTS: A total of 19,192 children completed
      the study satisfactorily. Physician-diagnosed asthma was reported in 6.6% of 5-yr
      old children. Pre-pregnancy factors (parental atopy and socioeconomic status),
      perinatal factors (place of residence, exposure to indoor mold and
      painting/renovations during pregnancy), and postnatal factors (maternal
      postpartum depression and the presence of atopic dermatitis before 6 months of
      age) were chosen for the predictive models, and the highest predicted probability
      of asthma in 5-yr-old children was 68.1% in boys and 78.1% in girls; the lowest
      probability in boys and girls was 4.1% and 3.2%, respectively. CONCLUSIONS: This
      investigation provides a technique for predicting risk of childhood asthma that
      can be used to developing a preventive strategy against asthma.

PMID- 25779975
TI  - The juxtamembrane regions of human receptor tyrosine kinases exhibit conserved
      interaction sites with anionic lipids.
AB  - Receptor tyrosine kinases (RTKs) play a critical role in diverse cellular
      processes and their activity is regulated by lipids in the surrounding membrane,
      including PIP2 (phosphatidylinositol-4,5-bisphosphate) in the inner leaflet, and
      GM3 (monosialodihexosylganglioside) in the outer leaflet. However, the precise
      details of the interactions at the molecular level remain to be fully
      characterised. Using a multiscale molecular dynamics simulation approach, we
      comprehensively characterise anionic lipid interactions with all 58 known human
      RTKs. Our results demonstrate that the juxtamembrane (JM) regions of RTKs are
      critical for inducing clustering of anionic lipids, including PIP2, both in
      simple asymmetric bilayers, and in more complex mixed membranes. Clustering is
      predominantly driven by interactions between a conserved cluster of basic
      residues within the first five positions of the JM region, and negatively charged
      lipid headgroups. This highlights a conserved interaction pattern shared across
      the human RTK family. In particular predominantly the N-terminal residues of the
      JM region are involved in the interactions with PIP2, whilst residues within the
      distal JM region exhibit comparatively less lipid specificity. Our results
      suggest that JM-lipid interactions play a key role in RTK structure and function,
      and more generally in the nanoscale organisation of receptor-containing cell
      membranes. 

PMID- 25779977
TI  - Non-local classical optical correlation and implementing analogy of quantum
      teleportation.
AB  - This study reports an experimental realization of non-local classical optical
      correlation from the Bell's measurement used in tests of quantum non-locality.
      Based on such a classical Einstein-Podolsky-Rosen optical correlation, a
      classical analogy has been implemented to the true meaning of quantum
      teleportation. In the experimental teleportation protocol, the initial teleported
      information can be unknown to anyone and the information transfer can happen over
      arbitrary distances. The obtained results give novel insight into quantum physics
      and may open a new field of applications in quantum information. 

PMID- 25779978
TI  - Controllable synthesis of mesoporous carbon nanospheres and Fe-N/carbon
      nanospheres as efficient oxygen reduction electrocatalysts.
AB  - The synthesis of mesoporous carbon nanospheres (MCNs), especially with diameters
      below 200 nm remains a great challenge due to weak interactions between the
      carbon precursors and soft templates, as well as the uncontrollable cross-linking
      rate of carbon precursors. Herein, we demonstrate a simple acid-assisted,
      hydrothermal synthesis approach to synthesizing such uniform MCNs with well
      controlled diameters ranging from 20 to 150 nm under highly acidic conditions (2
      M HCl). Both the carbon precursor and the template are partly protonated under
      such conditions and show additional Coulombic interactions with chloride ions
      (acts as mediators). This kind of enhanced interaction is similar to that of the
      "I(+)X(-)S(+)" mechanism in the synthesis of mesoporous metal oxide, which can
      effectively retard the cross-linking rate of resol molecules and avoid
      macroscopic phase separation during the hydrothermal synthesis. Due to their
      uniform spherical morphology, small diameter, and high surface areas, MCNs can be
      modified with Fe and N species via impregnation of cheap precursors (ferric
      nitrate and dicyandiamide), which are further converted into nonprecious
      electrocatalysts for oxygen reduction reactions. The resulting Fe-N/MCNs exhibit
      high catalytic activities, long-term stability and improved methanol tolerance
      under alkaline conditions, which can be potentially used in direct methanol fuel
      cells and metal-air batteries. 

PMID- 25779979
TI  - Interdependence of specialization and biodiversity in Phanerozoic marine
      invertebrates.
AB  - Studies of the dynamics of biodiversity often suggest that diversity has upper
      limits, but the complex interplay between ecological and evolutionary processes
      and the relative role of biotic and abiotic factors that set upper limits to
      diversity are poorly understood. Here we statistically assess the relationship
      between global biodiversity and the degree of habitat specialization of benthic
      marine invertebrates over the Phanerozoic eon. We show that variation in habitat
      specialization correlates positively with changes in global diversity, that is,
      times of high diversity coincide with more specialized faunas. We identify the
      diversity dynamics of specialists but not generalists, and origination rates but
      not extinction rates, as the main drivers of this ecological interdependence.
      Abiotic factors fail to show any significant relationship with specialization.
      Our findings suggest that the overall level of specialization and its
      fluctuations over evolutionary timescales are controlled by diversity-dependent
      processes--driven by interactions between organisms competing for finite
      resources.

PMID- 25779980
TI  - Identification of novel splice variants of the voltage- and Ca2+-dependent K+
      channel SLO-1 of Trichuris muris.
AB  - The anthelmintic cyclooctadepsipeptide emodepside is effective against nematodes
      showing resistance against established drug classes. Emodepside exerts its
      nematicidal effects mainly through its validated target, the tetrameric voltage-
      and calcium-activated potassium channel SLO-1. Two slo-1 genes were described in
      Trichuris muris. Alternative splicing is known to alter SLO-1 properties. Here,
      16 T. muris splice variants for slo-1.1 and three variants for slo-1.2 were
      identified in addition to previously described variants. Splice variants caused
      by intron retentions and/or exon exclusions encode varyingly truncated subunits.
      Depending on the subunit composition, channels might have altered physiological
      and pharmacological properties including different modulation by calcium and/or
      voltage or reduced emodepside susceptibility which might lead to emodepside
      resistance as observed in Caenorhabditis elegans expressing only similarly
      truncated Slo-1. The comprehensive characterisation of splice variants is a
      prerequisite for functional analysis and confirmed conservation of remarkable
      differences found between both slo-1 paralogs in Trichuris suis. 

PMID- 25779981
TI  - Strain induced modulation of the correlated transport in epitaxial Sm0.5Nd0.5NiO3
      thin films.
AB  - We report a study of the effect of epitaxial strain on the correlated transport
      properties of 2-40 nm Sm0.5Nd0.5NiO3 (SNNO) films grown on different substrates.
      The metal-insulator transition (MIT) temperature T(MI) of the SNNO films
      increases with increasing tensile strain. While films on (0 0 1) LaAlO3 and (1 1
      0) NdGaO3 substrates exhibit a sharp MIT and thermal hysteresis in the cooling
      heating cycle, signaling a first-order transition, films on (0 0 1) SrTiO3 show a
      broad, second-order MIT. Hall effect measurements reveal hole-type charge
      carriers and thermally activated temperature dependence of the carrier density
      below T(MI). The corresponding activation energy is ~80 meV for films on LaAlO3
      and NdGaO3, and is suppressed to 25 meV for films on SrTiO3. The carrier mobility
      in the metallic state and variable range hopping (VRH) transport at a low
      temperature point significantly enhanced electron localization in SNNO on STO,
      which we believe is not simply driven by extrinsic effects such as oxygen
      vacancies, but rather is an intrinsic characteristic for films subject to tensile
      strain due to the elongated Ni-O bond and hence enhanced dynamic Jahn-Teller
      distortion. In ultrathin films above the electrical dead layer thickness (2-3
      nm), we observe a more than 100 K increase of T(MI) for films on LaAlO3, which
      has been correlated with a crossover from 3D to 2D transport as revealed from
      VRH. We attribute the distinct transport characteristics to strain induced
      modulation of various energy scales associated with the Ni-O-Ni bond angle and Ni
      O bond length, which collectively determine the delocalization bandwidth of the
      system.

PMID- 25779982
TI  - Effect of width and boundary conditions on meeting maneuvers on two-way separated
      cycle tracks.
AB  - Cycle track design guidelines are rarely based on scientific studies. In the case
      of off-road two-way cycle tracks, a minimum width must facilitate both passing
      and meeting maneuvers, being meeting maneuvers the most frequent. This study
      developed a methodology to observe meeting maneuvers using an instrumented
      bicycle, equipped with video cameras, a GPS tracker, laser rangefinders and speed
      sensors. This bicycle collected data on six two-way cycle tracks ranging 1.3
      2.15m width delimitated by different boundary conditions. The meeting maneuvers
      between the instrumented bicycle and every oncoming bicycle were characterized by
      the meeting clearance between the two bicycles, the speed of opposing bicycle and
      the reaction of the opposing rider: change in trajectory, stop pedaling or
      braking. The results showed that meeting clearance increased with the cycle track
      width and decreased if the cycle track had lateral obstacles, especially if they
      were higher than the bicycle handlebar. The speed of opposing bicycle shown the
      same tendency, although were more disperse. Opposing cyclists performed more
      reaction maneuvers on narrower cycle tracks and on cycle tracks with lateral
      obstacles to the handlebar height. Conclusions suggested avoiding cycle tracks
      narrower than 1.6m, as they present lower meeting clearances, lower bicycle
      speeds and frequent reaction maneuvers. 

PMID- 25779983
TI  - Investigating the accuracy of Bayesian techniques for before-after safety
      studies: the case of a "no treatment" evaluation.
AB  - The main challenge in conducting observational before-after (BA) studies of road
      safety measures is to use a methodology that accounts for many potential
      confounding factors. However, it is usually difficult to evaluate and decide on
      the accuracy of the different safety evaluation techniques available in
      literature. This is mainly because the outcome of the comparison has no specific
      target (i.e., the effect of a specific treatment on safety is not precisely
      known). The objective of this paper is to compare the accuracy of some of the
      commonly used Bayesian methodologies for BA safety studies by applying them to
      locations where no safety treatment has been implemented (making the target
      result to be no effect). This goal was pursued within the setting of a specific
      case study where a recent set of collision data was available for urban
      signalized intersections in British Colombia (Canada) with no safety treatments
      implemented during the time frame considered. An assessment of the temporal
      stability of the data set was undertaken to exclude the presence of significant
      BA changes as explanation of the results reported in this paper. Both the well
      known empirical Bayes and the full Bayes method with non-linear intervention
      models were explored for comparison. Two types of selection of the hypothetical
      treatment sites were used in the analysis: random, to minimize the selection bias
      effect, and non-random, by selecting sites with abnormal collision frequency
      (hotspots). Several criteria were used for comparisons including variability
      among the index of effectiveness for individual treatment locations, the
      stability of the outcome in terms of the consistency of the results of several
      experiments and the overall treatment effectiveness. The results showed that when
      sites are selected randomly for treatment, all methodologies including the simple
      (naive) BA study provide reasonable results (small statistically non-significant
      change in collision frequency). However, when sites are selected for treatment
      because of high collision occurrence, the estimated index of treatment
      effectiveness can potentially be biased by values up to 10%. This finding can
      have significant impact on estimating safety benefits of treatments, especially
      on those that have low collision reductions. As well, the FB method seems to
      perform better than other evaluation techniques including the most commonly used
      EB method. In particular, the FB method provides higher consistency in the
      estimated collision reduction among treatment sites. 

PMID- 25779984
TI  - Parents' Recall and Reflections on Experiences Related to HPV Vaccination for
      Their Children.
AB  - Human papillomavirus (HPV) vaccination coverage remains suboptimal in the United
      States. We conducted in-depth interviews with parents of adolescents from an
      urban primary care center serving a low-income minority population to describe
      their experiences. We identified the following themes: (a) parents of
      unvaccinated children generally had not discussed the vaccine with providers and
      had low awareness; (b) among unaware parents, provision of brief information
      generally resulted in positive comments about the vaccine; (c) vaccine was
      typically not requested by parents but rather offered by providers; (d) strength
      of the recommendations from providers varied, and vaccine was sometimes presented
      as optional or low priority; (e) parents had low awareness of the three-dose
      regimen and poor recall about completion; and (f) limited understanding of why
      boys should be vaccinated. More than 7 years after the introduction of HPV
      vaccine, there is substantial room for improving the way it is recommended and
      discussed by providers. 

PMID- 25779985
TI  - Health/Service Providers' Perspectives on Barriers to Healthy Weight Gain and
      Physical Activity in Pregnant, Urban First Nations Women.
AB  - The purpose of this article is to examine health/service providers' perspectives
      of barriers to healthy weight gain and physical activity for urban, pregnant
      First Nations women in Ottawa, Canada. Through the use of semi-structured
      interviews, we explored 15 health/service providers' perspectives on the complex
      barriers their clients face. By using a postcolonial feminist lens and a social
      determinants of health framework, we identified three social determinants of
      health that the health/service providers believed to have the greatest influence
      on their clients' weight gain and physical activity during pregnancy: poverty,
      education, and colonialism. Our findings are then contextualized within existing
      Statistics Canada and the Ottawa Neighbourhood Study data. We found that
      health/service providers are in a position to challenge colonial relations of
      power. We conclude by urging health/service providers, researchers, and
      policymakers alike to take into consideration the ways in which these social
      determinants of health and their often synergistic effects affect urban First
      Nations women during pregnancy. 

PMID- 25779986
TI  - Modern clinical management helps reducing the impact of type 1 diabetes in
      children.
AB  - Type 1 diabetes care may be very costly not only in terms of money but also in
      terms of psychological and therapeutic acceptance and compliance. Recently, a lot
      of new technologies have been introduced in the care of patients with type 1
      diabetes that should allow them to achieve an improvement in glycemic control,
      quality of life and above all prevent long-term complications. Combining
      continuous glucose monitoring (CGM) and continuous subcutaneous insulin infusion
      (CSII) provides a more useful tool for patients with type 1 diabetes, the sensor
      augmented pump (SAP). The aim of the present review is to explore SAP efficacy
      and safety in young patients with type 1 diabetes. SAP demonstrated increased
      efficacy in lowering glycated hemoglobin when compared either to multiple daily
      injections or CSII alone. Its efficacy is positively associated with CGM use,
      baseline HbA1c and patients' age. According to currently available evidence, SAP
      seems sufficiently safe, effective and beneficial in improving glycemic control
      in pediatric patients with type 1 diabetes. Moreover, encouraging results using
      semi-closed loop systems are emerging, paving the way toward a fully automated
      artificial pancreas. As pediatric diabetologists we have the duty to offer our
      patients the best therapeutic option currently available, supported by evidence,
      to help them gain the best results with the fewest adverse effects (hypoglycemia
      and/or diabetic ketoacidosis), better if chomping a little piece of dark
      chocolate. 

PMID- 25779988
TI  - Interfacing graphene and related 2D materials with the 3D world.
AB  - An important prerequisite to translating the exceptional intrinsic performance of
      2D materials such as graphene and transition metal dichalcogenides into useful
      devices precludes their successful integration within the current 3D technology.
      This review provides theoretical insight into nontrivial issues arising from
      interfacing 2D materials with 3D systems including epitaxy and ways to
      accommodate lattice mismatch, the key role of contact resistance and the effect
      of defects in electrical and thermal transport. 

PMID- 25779987
TI  - GlycA: A Composite Nuclear Magnetic Resonance Biomarker of Systemic Inflammation.
AB  - BACKGROUND: Nuclear magnetic resonance (NMR) spectra of serum obtained under
      quantitative conditions for lipoprotein particle analyses contain additional
      signals that could potentially serve as useful clinical biomarkers. One of these
      signals that we named GlycA originates from a subset of glycan N
      acetylglucosamine residues on enzymatically glycosylated acute-phase proteins. We
      hypothesized that the amplitude of the GlycA signal might provide a unique and
      convenient measure of systemic inflammation. METHODS: We developed a spectral
      deconvolution algorithm to quantify GlycA signal amplitudes from automated NMR
      LipoProfile((r)) test spectra and assessed analytic precision and biological
      variability. Spectra of acute-phase glycoproteins and serum fractions were
      analyzed to probe the origins of the GlycA signal. GlycA concentrations obtained
      from archived NMR LipoProfile spectra of baseline plasma from 5537 participants
      in the Multi-Ethnic Study of Atherosclerosis (MESA) were used to assess
      associations with demographic and laboratory parameters including measures of
      inflammation. RESULTS: Major acute-phase protein contributors to the serum GlycA
      signal are alpha1-acid glycoprotein, haptoglobin, alpha1-antitrypsin, alpha1
      antichymotrypsin, and transferrin. GlycA concentrations were correlated with high
      sensitivity C-reactive protein (hsCRP) (r = 0.56), fibrinogen (r = 0.46), and
      interleukin-6 (IL-6) (r = 0.35) (all P < 0.0001). Analytic imprecision was low
      (intra- and interassay CVs 1.9% and 2.6%, respectively) and intraindividual
      variability, assessed weekly for 5 weeks in 23 healthy volunteers, was 4.3%,
      lower than for hsCRP (29.2%), cholesterol (5.7%), and triglycerides (18.0%).
      CONCLUSIONS: GlycA is a unique inflammatory biomarker with analytic and clinical
      attributes that may complement or provide advantages over existing clinical
      markers of systemic inflammation.

PMID- 25779989
TI  - Thermoelectric effects in graphene nanostructures.
AB  - The thermoelectric properties of graphene and graphene nanostructures have
      recently attracted significant attention from the physics and engineering
      communities. In fundamental physics, the analysis of Seebeck and Nernst effects
      is very useful in elucidating some details of the electronic band structure of
      graphene that cannot be probed by conductance measurements alone, due in
      particular to the ambipolar nature of this gapless material. For applications in
      thermoelectric energy conversion, graphene has two major disadvantages. It is
      gapless, which leads to a small Seebeck coefficient due to the opposite
      contributions of electrons and holes, and it is an excellent thermal conductor.
      The thermoelectric figure of merit ZT of a two-dimensional (2D) graphene sheet is
      thus very limited. However, many works have demonstrated recently that
      appropriate nanostructuring and bandgap engineering of graphene can concomitantly
      strongly reduce the lattice thermal conductance and enhance the Seebeck
      coefficient without dramatically degrading the electronic conductance. Hence, in
      various graphene nanostructures, ZT has been predicted to be high enough to make
      them attractive for energy conversion. In this article, we review the main
      results obtained experimentally and theoretically on the thermoelectric
      properties of graphene and its nanostructures, emphasizing the physical effects
      that govern these properties. Beyond pure graphene structures, we discuss also
      the thermoelectric properties of some hybrid graphene structures, as graphane,
      layered carbon allotropes such as graphynes and graphdiynes, and
      graphene/hexagonal boron nitride heterostructures which offer new opportunities.
      Finally, we briefly review the recent activities on other atomically thin 2D
      semiconductors with finite bandgap, i.e. dichalcogenides and phosphorene, which
      have attracted great attention for various kinds of applications, including
      thermoelectrics. 

PMID- 25779990
TI  - Is volunteering in later life impeded or stimulated by other activities?
AB  - PURPOSE: Volunteering among older adults has received increasing attention from
      researchers, policy makers, and associations. However, there remains a lack of
      knowledge in how volunteering is impacted by other activities in the lives of
      older adults. In order to understand activity engagement in later life, insights
      into the extent to which activities compete with or complement each other are
      necessary. METHODS: Data for the present research were derived from the Belgian
      Aging Studies (N = 23,768). The main objective is to uncover the activities that
      impede or stimulate actual volunteering and/or the likeliness to volunteer at an
      older age. RESULTS: Structural equation models indicate a strong positive
      correlation between altruistic types of activities and actual volunteering.
      Furthermore, older adults active in personal leisure activities are more drawn to
      be potential volunteers. IMPLICATIONS: The article demonstrates that the activity
      level of older people is not sufficient to understand volunteering, that is, a
      distinction between the types of activities is essential.

PMID- 25779991
TI  - Tensor-based dictionary learning for dynamic tomographic reconstruction.
AB  - In dynamic computed tomography (CT) reconstruction, the data acquisition speed
      limits the spatio-temporal resolution. Recently, compressed sensing theory has
      been instrumental in improving CT reconstruction from far few-view projections.
      In this paper, we present an adaptive method to train a tensor-based spatio
      temporal dictionary for sparse representation of an image sequence during the
      reconstruction process. The correlations among atoms and across phases are
      considered to capture the characteristics of an object. The reconstruction
      problem is solved by the alternating direction method of multipliers. To recover
      fine or sharp structures such as edges, the nonlocal total variation is
      incorporated into the algorithmic framework. Preclinical examples including a
      sheep lung perfusion study and a dynamic mouse cardiac imaging demonstrate that
      the proposed approach outperforms the vectorized dictionary-based CT
      reconstruction in the case of few-view reconstruction. 

PMID- 25779992
TI  - Independent dose calculations for commissioning, quality assurance and dose
      reconstruction of PBS proton therapy.
AB  - Pencil beam scanning proton therapy allows the delivery of highly conformal dose
      distributions by delivering several thousand pencil beams. These beams have to be
      individually optimised and accurately delivered requiring a significant quality
      assurance workload. In this work we describe a toolkit for independent dose
      calculations developed at Paul Scherrer Institut which allows for dose
      reconstructions at several points in the treatment workflow. Quality assurance
      based on reconstructed dose distributions was shown to be favourable to pencil
      beam by pencil beam comparisons for the detection of delivery uncertainties and
      estimation of their effects. Furthermore the dose reconstructions were shown to
      have a sensitivity of the order of or higher than the measurements currently
      employed in the clinical verification procedures. The design of the independent
      dose calculation tool allows for a high modifiability of the dose calculation
      parameters (e.g. depth dose profiles, angular spatial distributions) allowing for
      a safe environment outside of the clinical treatment planning system for
      investigating the effect of such parameters on the resulting dose distributions
      and thus distinguishing between different contributions to measured dose
      deviations. The presented system could potentially reduce the amount of patient
      specific quality assurance measurements which currently constitute a bottleneck
      in the clinical workflow.

PMID- 25779993
TI  - To screen or not to screen: that is not (yet) the question.

PMID- 25779994
TI  - Added value of screening for CKD among the elderly or persons with low
      socioeconomic status.
AB  - BACKGROUND AND OBJECTIVE: Three screening approaches were compared for their
      ability to detect CKD cases, and identify patients with CKD who have a higher
      rate of incident cardiovascular disease (CVD) events and renal function decline.
      Approach 1 was the traditional CKD screening approach, targeting only individuals
      with known diabetes, hypertension, or CVD history. Approach 2 was defined as
      Approach 1+elderly, and Approach 3 as Approach 1+low-socioeconomic status (SES)
      individuals. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Data on 3411
      individuals from the general population in The Netherlands were examined.
      Individuals aged >60 years were classified as elderly. Persons with low SES was
      defined as those with primary school or below primary school education. CKD was
      diagnosed during outpatient clinic visits. Individuals were followed for 9.4+/
      2.6 years during four screening rounds. RESULTS: At baseline, 16%, 29%, and 25%
      of the general population was to be screened and 36%, 59%, and 51% of the CKD
      (n=263) cases were detected in Approaches 1, 2, and 3, respectively. The numbers
      of individuals needed to screen to detect one CKD case were 5.6 in Approach 1 and
      6.5 each in Approach 2 and 3. In Approach 2 the hazard ratio for incident CVD
      events was 1.87 (95% confidence interval [95% CI], 1.35 to 2.61) in detected and
      1.92 (95% CI, 1.01 to 3.64) in undetected CKD cases compared with persons without
      CKD, whereas in Approach 3 these values were 2.31 (95% CI, 1.64 to 3.25) and 1.28
      (95% CI, 0.77 to 2.13), respectively. In Approach 2, the rate of renal function
      decline was -1.37 ml/min per 1.73 m(2) per year in detected and -1.13 ml/min per
      1.73 m(2) per year in undetected CKD cases. In Approach 3, these figures were 
      1.41 and -1.14 ml/min per 1.73 m(2) per year, respectively. CONCLUSIONS: Adding
      persons with low SES, rather than adding elderly persons, to the traditional high
      risk groups may help detect more persons with CKD who have a higher rate of
      future CVD events and renal function decline.

PMID- 25779996
TI  - Can molecular subtyping be used to guide metastatic screening in breast cancer?

PMID- 25779995
TI  - Mouse Ovarian Very Small Embryonic-Like Stem Cells Resist Chemotherapy and Retain
      Ability to Initiate Oocyte-Specific Differentiation.
AB  - This study was undertaken to investigate stem cells in adult mouse ovary, the
      effect of chemotherapy on them and their potential to differentiate into germ
      cells. Very small embryonic-like stem cells (VSELs) that were SCA-1+/Lin-/CD45-,
      positive for nuclear octamer-binding transforming factor 4 (OCT-4), Nanog, and
      cell surface stage-specific embryonic antigen 1, were identified in adult mouse
      ovary. Chemotherapy resulted in complete loss of follicular reserve and
      cytoplasmic OCT-4 positive progenitors (ovarian germ stem cells) but VSELs
      survived. In ovarian surface epithelial (OSE) cell cultures from chemoablated
      ovary, proliferating germ cell clusters and mouse vasa homolog/growth
      differentiation factor 9-positive oocyte-like structure were observed by day 6,
      probably arising as a result of differentiation of the surviving VSELs. Follicle
      stimulating hormone (FSH) exerted a direct stimulatory action on the OSE and
      induced stem cells proliferation and differentiation into premeiotic germ cell
      clusters during intact chemoablated ovaries culture. The FSH analog pregnant mare
      serum gonadotropin treatment to chemoablated mice increased the percentage of
      surviving VSELs in ovary. The results of this study provide evidence for the
      presence of potential VSELs in mouse ovaries and show that they survive
      chemotherapy, are modulated by FSH, and retain the ability to undergo oocyte
      specific differentiation. These results show relevance to women who undergo
      premature ovarian failure because of oncotherapy. 

PMID- 25779997
TI  - Breast cancer subtypes predispose the site of distant metastases.
AB  - OBJECTIVES: The distant organs to which breast cancer preferentially metastasizes
      are of significant clinical importance. METHODS: We explored the relationship
      between the clinicopathologic factors and the common sites of distant metastasis
      in 531 consecutive patients with advanced breast cancer. RESULTS: Breast cancer
      subtype as a variable was significantly associated with all five common sites of
      relapse by multivariate analysis. The luminal tumors were remarkable for their
      significant bone-seeking phenotype and were less frequently observed in lung,
      brain, and pleural metastases and less likely to be associated with multiorgan
      relapse. The HER2 subtype demonstrated a significant liver-homing characteristic.
      African Americans were significantly less likely to have brain-only metastasis in
      patients with brain relapse. CONCLUSIONS: These findings further articulate that
      breast cancer subtypes differ not only in tumor characteristics but also in their
      metastatic behavior, thus raising the possibility that this knowledge could
      potentially be used in determining the appropriate strategy for follow-up of
      patients with newly diagnosed breast cancer.

PMID- 25779999
TI  - Follow-up outcomes in a large cohort of patients with HPV-negative LSIL cervical
      screening test results.
AB  - OBJECTIVES: Cervical screening guidelines now recommend repeat cotesting of
      patients aged 30 years and older having a human papillomavirus (HPV)-negative low
      grade squamous intraepithelial lesion (LSIL) in 1 year as preferred management.
      Only limited follow-up data on patients with HPV-negative LSILs are available
      from routine US clinical practice settings. METHODS: In total, 680 patients with
      Hybrid Capture 2 (Qiagen, Hinden, Germany) high-risk HPV-negative LSIL ThinPrep
      (Hologic, Marlborough, MA) results were identified. Patients' ages and
      histopathologic, cytologic, and HPV follow-up results were identified. RESULTS:
      Among 680 patients with HPV-negative LSILs, 468 had follow-up within 1 year.
      During the study period, 14 (3.0%) of 468 had follow-up high-grade squamous
      intraepithelial lesion (HSIL) and 184 (39.3%) LSIL findings. No diagnoses of
      cervical carcinoma were documented. There were no significant follow-up
      differences between age groups. Of the 321 patients who had follow-up HPV
      testing, 271 (84.4%) had negative and 50 (15.6%) had positive HPV results.
      CONCLUSIONS: This is the largest study documenting follow-up results for patients
      with HPV-negative LSIL results based on prevalent US FDA-approved co-testing
      methods from one collection vial. These data document that risk for follow-up
      HSILs in these patients is low and also that no cervical cancers were diagnosed.
      These findings support recent recommendations for repeat co-testing after 1 year
      as an appropriate option for patients with HPV-negative LSIL results.

PMID- 25779998
TI  - Evaluation of treponemal serum tests performed on cerebrospinal fluid for
      diagnosis of neurosyphilis.
AB  - OBJECTIVES: We evaluated the use of treponemal serum tests in cerebrospinal fluid
      (CSF) to diagnose neurosyphilis since CSF-Venereal Disease Research Laboratory
      (VDRL) is specific but lacks sensitivity. METHODS: We tested CSF specimens using
      the following treponemal serum tests: INNO-LIA, Treponema pallidum particle
      agglutination (TP-PA), Trep-Sure, and Maxi-Syph. The reference standard to
      calculate sensitivity and specificity was having two or more reactive/positive
      tests on CSF. RESULTS: The reference standard group included 11 cases that
      fulfilled the definition of neurosyphilis (reactive CSF-VDRL plus symptoms) and
      three cases that did not fulfill the definition: two cases had neurologic
      symptoms but a nonreactive CSF-VDRL, and one had several positive CSF syphilis
      tests (reactive VDRL and positive treponemal and syphilis polymerase chain
      reaction) but no history (referred sample). Controls included 18 patients in whom
      a CSF-VDRL was performed the same week as patients in the reference group. The
      sensitivity was 85.7% (12/14) for CSF-VDRL, 92.9% (13/14) for Trep-Sure, 100%
      (10/10) for Maxi-Syph, 92.3% (12/13) for INNO-LIA, and 83.3% (10/12) for TP-PA.
      Specificity was 100% for all tests. CONCLUSIONS: Treponemal serum tests performed
      on CSF were useful in identifying two patients with nonreactive CSF-VDRL.

PMID- 25780000
TI  - Relationship of pathologic factors to efficacy of sorafenib treatment in patients
      with metastatic clear cell renal cell carcinoma.
AB  - OBJECTIVES: To evaluate the predictive value of growth patterns in patients
      undergoing sorafenib treatment for metastatic clear cell renal cell carcinomas
      (CCRCCs). METHODS: Forty-eight patients were analyzed, each of whom underwent
      nephrectomy and received sorafenib treatment for metastatic CCRCC. Progression
      free survival (PFS) was predicted using pathologic parameters, including
      pathologic stage, Fuhrman nuclear grade (FNG), the presence of a sarcomatoid
      component, lymphovascular invasion, tumor necrosis, and growth pattern. RESULTS:
      Three (6%) patients showed partial response, 20 (42%) patients showed stable
      disease, and 25 (52%) patients showed progressive disease. Univariate analyses
      demonstrated that FNG, the presence of a sarcomatoid component, tumor necrosis,
      and growth pattern were significantly associated with PFS. In the multivariate
      analysis, growth pattern was the only parameter that was significantly and
      independently predictive of PFS. CONCLUSIONS: As a novel histologic prognostic
      parameter, growth pattern may be useful for predicting response to sorafenib
      treatment.

PMID- 25780001
TI  - Detection of BRAF mutations on direct smears of thyroid fine-needle aspirates
      through cell transfer technique.
AB  - OBJECTIVES: To determine the utility of the cell transfer technique (CTT) for
      BRAF molecular testing on thyroid fine-needle aspiration (FNA) specimens.
      METHODS: Polymerase chain reaction (PCR)-based BRAF molecular testing was
      performed on tissues obtained through CTT from both air-dried and ethanol-fixed
      direct smears of thyroid FNA specimens and then compared with the corresponding
      thyroidectomy formalin-fixed, paraffin-embedded (FFPE) tissues on 30 cases.
      RESULTS: BRAF testing was successfully performed on 29 of 30 air-dried CTT, 27 of
      30 ethanol-fixed CTT, and 27 of 30 FFPE tissues. The results exhibited 11, 13,
      and 13 BRAF mutations and 18, 14, and 14 wild types for the air-dried CTT, the
      ethanol-fixed CTT, and the FFPE tissues, respectively. The concordance rate was
      96% between air-dried and ethanol-fixed CTT tissues, 88% between air-dried CTT
      and FFPE tissues, and 92% between ethanol-fixed CTT and FFPE tissues.
      CONCLUSIONS: PCR-based BRAF mutational testing can be reliably performed on the
      direct smears of the thyroid FNA specimens through the application of CTT.

PMID- 25780002
TI  - Primary sclerosing cholangitis: detailed histologic assessment and integration
      using bioinformatics highlights arterial fibrointimal hyperplasia as a novel
      feature.
AB  - OBJECTIVES: Liver biopsy diagnosis of primary sclerosing cholangitis (PSC) is
      difficult. We performed a detailed histologic analysis of PSC cases using novel
      bioinformatics analysis to identify histologic features that may be useful in its
      diagnosis. METHODS: PSC liver explants were examined and compared with primary
      biliary cirrhosis and hepatitis C explants to act as controls. Demographic,
      macroscopic, and histologic variables were analyzed using both conventional
      statistics and an integrative bioinformatics approach, significance analysis of
      microarrays (SAM), and hierarchical clustering analysis (HCA). RESULTS: The PSC
      group was younger and had distinctive PSC features, including bile duct scars,
      onion-skin fibrosis, and arterial fibrointimal hyperplasia. SAM allowed the
      integration of variables by comparing PSC and control groups, whereas HCA was
      able to correctly categorize each group. CONCLUSIONS: This study demonstrates
      characteristic PSC histology as well as arterial hyperplasia to be distinctive
      features that may aid in PSC diagnosis and be confirmed by bioinformatics.

PMID- 25780003
TI  - Expression of Bcl-xL and Mcl-1 in the nonmelanoma skin cancers of renal
      transplant recipients.
AB  - OBJECTIVES: This study aims to investigate how immunosuppression influences the
      protein expression of antiapoptotic members of the Bcl-2 family-namely, Bcl-xL
      and Mcl-1-in nonmelanoma skin cancer (NMSC) and the peritumoral epidermis of
      renal transplant recipients. METHODS: NMSC and peritumoral epidermis protein
      expression of Bcl-xL and Mcl-1 were assessed by immunohistochemistry in renal
      transplant recipients receiving tacrolimus or sirolimus and the general
      population not receiving immunosuppression. RESULTS: NMSC from renal transplant
      recipients compared with patients not receiving immunosuppressant medications had
      a reduced Bcl-xL expression intensity (P = .042). Mcl-1 expression intensity in
      NMSC was decreased in tacrolimus-treated patients compared with sirolimus-treated
      patients and the nonimmunosuppressed population (P = .024). Bcl-xL expression
      intensity was increased in peritumoral epidermis compared with NMSC (P = .002).
      CONCLUSIONS: It was shown for the first time that Bcl-xL and Mcl-1 expression are
      widespread in the peritumoral epidermis and NMSC of renal transplant recipients.
      Importantly in NMSC, Bcl-xL expression was reduced with immunosuppression
      exposure, and Mcl-1 expression was reduced in tacrolimus-treated compared with
      sirolimus-treated patients.

PMID- 25780004
TI  - Mast cells in systemic mastocytosis have distinctly brighter CD45 expression by
      flow cytometry.
AB  - OBJECTIVES: We sought to determine the significance of bright CD45 expression on
      mast cells in cases of systemic mastocytosis vs mast cells in bone marrows
      uninvolved by systemic mastocytosis and compare this CD45 expression with CD25
      and CD2 expression on mast cells. METHODS: Multiparameter flow cytometry was
      performed on 31 cases of systemic mastocytosis and 70 bone marrow cases that were
      not involved by systemic mastocytosis. Bright expression of CD45 was defined as
      more than 20% of CD117+ mast cells showing brighter CD45 expression than the
      average expression level of lymphocytes. RESULTS: Mast cells with bright CD45
      expression were seen in 26 systemic mastocytosis cases and three bone marrows
      uninvolved by systemic mastocytosis (sensitivity, 84%; specificity, 96%). CD25
      alone had a greater sensitivity (100%) but lower specificity (93%) compared with
      bright CD45 for identifying abnormal mast cells, while CD2 alone had lower
      sensitivity but higher specificity. To reach a specificity of 100%, CD25 together
      with bright CD45 on mast cells was the optimal combination to detect cases of
      systemic mastocytosis. CONCLUSIONS: A combination of bright CD45 and CD25 appears
      to specifically identify abnormal mast cells in cases of systemic mastocytosis.
      Further studies will be necessary to confirm these results.

PMID- 25780005
TI  - Adequacy of powered vs manual bone marrow biopsy specimens: a retrospective
      review of sequential marrow aspirates and biopsies in 68 patients.
AB  - OBJECTIVES: To evaluate the quality and quantity of the bone marrow aspirates and
      biopsy specimens obtained with a powered system in comparison with the standard
      manual method. METHODS: The Pathology Laboratory Information System was reviewed
      for patients who had previously undergone bone marrow biopsies performed by both
      the OnControl Bone Marrow System and the manual method. A total of 136 cases (68
      patients) were reviewed for adequacy and compared using an unpaired t test.
      RESULTS: The core biopsy specimens obtained by the OnControl system were
      significantly longer compared with those obtained by the manual system (16.9 vs
      14.4 mm, P = .0036). However, the core biopsy specimens obtained by the manual
      method had on average more evaluable marrow elements (66% vs 40%, P < .0001), and
      the manual method was superior in 46 of the 68 cases when the length of evaluable
      marrow was calculated (9.7 vs 7 mm, P = .0049). CONCLUSIONS: Our findings show
      that longer core biopsy specimens are obtained by the OnControl Bone Marrow
      system but that the manual method is still superior when the percentage and
      length of evaluable bone marrow are analyzed.

PMID- 25780006
TI  - Clinicopathologic relevance of claudin 5 expression in breast cancer.
AB  - OBJECTIVES: Claudins are major adhesion molecules in tight junctions and are
      strongly expressed in various cancers. We thus investigated the expression of
      claudin 5, a member of the claudin family, in breast cancer. METHODS: A total of
      193 patients with breast cancer were identified based on their pathologic
      diagnosis. The expression of each claudin 5 was analyzed in the tumor by
      immunohistochemical staining. Parametric correlations were done between claudin 5
      expression and the clinicopathologic findings. RESULTS: Claudin 5 expression in
      patients with recurrent breast cancer was statistically significantly higher (P =
      .004). In addition, analysis of the correlation with other clinicopathologic
      factors showed statistically significant differences with respect to lymphatic
      invasion (P = .014), venous invasion (P = .048), estrogen receptor status (P =
      .002), and human epidermal growth factor 2 status (P = .007). Multivariate
      analysis revealed that claudin 5 expression was an independent predictive factor
      in the recurrence for relapse-free survival (RFS) (P = .020). Kaplan-Meier
      analysis showed that the RFS rate was significantly lower in the high claudin 5
      expression group (P = .001). CONCLUSIONS: Patients with breast cancer with high
      claudin 5 expression had a significantly lower RFS rate. Our findings suggest
      that claudin 5 may be useful as a new biomarker of a risk factor.

PMID- 25780007
TI  - BCL6 expression correlates with the t(1;19) translocation in B-lymphoblastic
      leukemia.
AB  - OBJECTIVES: Study to date suggests that BCL6 protein expression in B-cell
      neoplasia predominates in germinal center-derived tumors, but less is known
      regarding its expression in B-lymphoblastic leukemia. Therefore, we designed a
      comprehensive study of BCL6 expression in B-lymphoblastic leukemia. METHODS:
      BCL6, LMO, and HGAL protein expression in B-lymphoblastic leukemia was
      investigated using immunohistochemical staining of paraffin-embedded bone marrow
      specimens. Cryptic TCF3(E2A)-PBX1 rearrangements were investigated using
      interphase fluorescence in situ hybridization. RESULTS: Six (12%) of 52 B
      lymphoblastic leukemias demonstrated BCL6 protein expression, with B-cell
      lymphoblastic leukemias containing a t(1;19) translocation demonstrating the
      strongest staining (three of three). Additional t(1;19) cases beyond the
      screening study showed similar results. Public microarray expression database
      mining showed that BCL6 messenger RNA expression levels in B-lymphoblastic
      leukemia correlated with the protein expression findings. Finally, other markers
      of B-cell development correlated with BCL6 expression in t(1;19) B-lymphoblastic
      leukemia cases, with LMO2 and HGAL proteins expressed in six (67%) of nine and
      eight (89%) of nine cases, respectively. CONCLUSIONS: BCL6 expression is present
      in a subset of B-lymphoblastic leukemias, especially in cases containing the 1;19
      translocation. Investigation for TCF3(E2A)-PBX1 rearrangements may be useful in
      BCL6-positive B-lymphoblastic leukemia.

PMID- 25780008
TI  - Effect of blood sampling, processing, and storage on the measurement of
      complement activation biomarkers.
AB  - OBJECTIVES: Recent studies have shown that complement hyperactivation contributes
      to development of thrombotic microangiopathy. The evaluation of complement
      biomarkers is known to be influenced by inappropriate specimen handling. However,
      there has been no study fully addressing this topic. METHODS: Blood from each
      donor was subjected to 62 different handling conditions prior to complement
      assays. RESULTS: Complement biomarkers (C4d/C3a/factor Bb/C5a/C5b-9) are stable
      at room temperature (RT) for up to 4 hours in whole blood containing citrate or
      EDTA. However, under similar conditions, levels of C4d and C3a were significantly
      higher in serum than those in plasma. Thawing of the samples on ice or at RT had
      no significant effect on complement levels. In contrast, thawing at 37 degrees C
      resulted in striking increases in levels of the complement system in serum and
      citrated plasma but not in EDTA plasma. Up to four freeze/thaw cycles on ice or
      RT did not substantially increase the levels of C3a, factor Bb, C5a, and C5b-9
      but had a significant effect on C4d. Long-term storage of citrated plasma at -80
      degrees C for up to 6 years had no significant effect on levels of complement
      factors. CONCLUSIONS: The results from this study thus provide crucial guidelines
      for future investigations using complement biomarkers to define the role of
      complement system in disease.

PMID- 25780009
TI  - Laboratory quality improvement in Tanzania.
AB  - OBJECTIVES: The article describes the implementation and improvement in the first
      groups of medical laboratories in Tanzania selected to participate in the
      training program on Strengthening Laboratory Management Toward Accreditation
      (SLMTA). METHODS: As in many other African nations, the selected improvement plan
      consisted of formalized hands-on training (SLMTA) that teaches the tasks and
      skills of laboratory management and provides the tools for implementation of best
      laboratory practice. Implementation of the improvements learned during training
      was verified before and after SLMTA with the World Health Organization African
      Region Stepwise Laboratory Improvement Process Towards Accreditation checklist.
      RESULTS: During a 4-year period, the selected laboratories described in this
      article demonstrated improvement with a range of 2% to 203% (cohort I) and 12% to
      243% (cohort II) over baseline scores. CONCLUSIONS: The article describes the
      progress made in Tanzania's first cohorts, the obstacles encountered, and the
      lessons learned during the pilot and subsequent implementations.

PMID- 25780010
TI  - Comparison of next-generation sequencing and mutation-specific platforms in
      clinical practice.
AB  - OBJECTIVES: To compare next-generation sequencing (NGS) platforms with mutation
      specific analysis platforms in a clinical setting, in terms of sensitivity,
      mutation specificity, costs, capacity, and ease of use. METHODS: We analyzed 25
      formalin-fixed, paraffin-embedded lung cancer samples of different size and tumor
      percentage for known KRAS and EGFR hotspot mutations with two dedicated
      genotyping platforms (cobas [Roche Diagnostics, Almere, The Netherlands] and
      Rotor-Gene [QIAGEN, Venlo, The Netherlands]) and two NGS platforms (454 Genome
      Sequencer [GS] junior [Roche Diagnostics] and Ion Torrent Personal Genome Machine
      [Life Technologies, Bleiswijk, The Netherlands]). RESULTS: All platforms, except
      the 454 GS junior, detected the mutations originally detected by Sanger
      sequencing and high-resolution melting prescreening and detected an additional
      KRAS mutation. The dedicated genotyping platforms outperformed the NGS platforms
      in speed and ease of use. The large sequencing capacity of the NGS platforms
      enabled them to deliver all mutation information for all samples at once.
      CONCLUSIONS: Sensitivity for detecting mutations was highly comparable among all
      platforms. The choice for either a dedicated genotyping platform or an NGS
      platform is basically a trade-off between speed and genetic information.

PMID- 25780011
TI  - Validation of hemolysis index thresholds optimizes detection of clinically
      significant hemolysis.
AB  - OBJECTIVES: Automated hemolysis index (HI) measurement has standardized the
      identification and gradation of sample hemolysis. METHODS: This study evaluates
      whether clinically significant changes in the concentration of intracellular
      analytes occur at manufacturer-recommended automated HI thresholds (HI >=3, >25
      mg/dL hemoglobin). RESULTS: Adult outpatient results for serum potassium (K+),
      magnesium (Mg), lactate dehydrogenase (LDH), and aspartate aminotransferase (AST)
      were analyzed. Mean +/- SD analyte concentration and distribution within the
      reference interval (RI) were calculated for each HI group (1-7). Potassium
      results with an HI of 4 or more demonstrated clinically significant differences
      (>=0.5 mmol/L) in mean K+ concentration and RI classification compared with non
      hemolyzed samples (HI = 1). LDH and AST showed clinically significant differences
      (+20%) for an HI of 3 or more. For Mg, only the group with an HI of 7
      demonstrated a clinically significant difference (>25%); however, the number was
      low. CONCLUSIONS: Mean measured potassium concentrations are not clinically
      significantly affected by hemolysis at the manufacturer-recommended HI threshold,
      while AST and LDH are. Aligning reporting of sample hemolysis with clinically
      significant changes provides clinically meaningful alerts regarding this common
      pre-analytic error.

PMID- 25780012
TI  - Expression of metabolism-related proteins in lacrimal gland adenoid cystic
      carcinoma.
AB  - OBJECTIVES: To investigate the expression and the clinical implications of
      metabolism-related proteins in lacrimal gland adenoid cystic carcinoma (ACC) in
      comparison with salivary gland ACC. METHODS: Human tissue samples of lacrimal
      gland ACC (n = 11) and salivary gland ACC (n = 64) were analyzed. Immunochemistry
      was used to measure expression of proteins related to glycolysis (glucose
      transporter 1, hexokinase II, carbonic anhydrase IX, and monocarboxylate
      transporter 4 [MCT4]), glutaminolysis (glutaminase 1 [GLS1], glutamate
      dehydrogenase [GDH], and amino acid transporter 2 [ASCT2]), mitochondria
      (adenosine triphosphate [ATP] synthase, succinate dehydrogenase A [SDHA], and
      succinate dehydrogenase B), and glycolytic intermediate metabolism (phosphoserine
      phosphatase [PSPH], serine hydroxymethyl transferase 1 [SHMT1]). RESULTS: GLS1
      and ASCT2 were more highly expressed, and GDH, ATP synthase, and SDHA were
      expressed to a lesser degree in lacrimal gland ACC than in salivary gland ACC (P
      < .05). Lacrimal gland ACC showed less of a mitochondrial phenotype than did
      salivary gland ACC (P = .001). Positivity of MCT4 and PSPH was related to shorter
      disease-free survival, and SHMT1 was related to shorter overall survival (P <
      .05). CONCLUSIONS: Lacrimal gland ACC exhibited higher expression of GLS1 and
      ASCT2, compared with salivary gland ACC. Overexpression of MCT4, PSPH, and SHMT1
      was associated with poorer prognosis.

PMID- 25780013
TI  - Dermatopathologists' opinions about the quality of clinical information in the
      skin biopsy requisition form and the skin biopsy care process: a semiqualitative
      assessment.
AB  - OBJECTIVES: The skin biopsy care process is prone to communication failures. We
      sought to solicit dermatopathologists about their opinions on the quality of
      clinical information provided in the requisition form (RF) that accompanies skin
      specimens and their suggestions on how to improve the process. METHODS: A self
      administered survey of the membership of the American Society of Dermatopathology
      was performed. Qualitative methods were used to analyze free-text comments.
      RESULTS: Of 1,102 participants, 153 completed the final question in the survey
      (response rate 14%). Respondent opinions fell into four critical themes: (1)
      quality of clinical information in the RF and adequacy of biopsy specimens, (2)
      training of residents and nondermatologist providers, (3) information transfer
      via electronic medical records, and (4) practice constraints. CONCLUSIONS:
      Dermatopathologists communicated that missing clinical information in the RF and
      inadequate specimens are common and adversely affect the quality of care.
      Multiple provider- and practice-related factors contribute to communication
      failures and deserve further investigation.

PMID- 25780014
TI  - Clinicopathologic evaluation of MYC expression in primary mediastinal (thymic)
      large B-cell lymphoma.
AB  - OBJECTIVES: Based on previous molecular studies, a small fraction of primary
      mediastinal (thymic) large B-cell lymphoma (PMBL) demonstrates MYC alterations.
      However, no studies have evaluated MYC protein expression by immunohistochemistry
      (IHC) with follow-up fluorescence in situ hybridization (FISH) analysis. We aim
      to evaluate the clinicopathologic importance of MYC IHC expression in PMBL.
      METHODS: Three pathologists independently evaluated MYC IHC expression in 32
      cases of PMBL for percent tumor positivity and nuclear intensity. FISH analysis
      for MYC rearrangement was performed on cases with high MYC IHC expression.
      Clinical data including treatment, follow-up, and outcome were also reviewed in a
      subset of cases. RESULTS: Variable MYC protein expression by IHC was detected in
      30 (94%) of 32 cases of PMBL. One-third of the positive cases (10/30) showed high
      MYC IHC expression of at least 30% nuclear positivity. FISH analyses for MYC
      rearrangement on these 10 cases were negative. Review of clinical data on a
      subset of cases with high and low MYC IHC expression showed no differences in
      clinical outcome. CONCLUSIONS: MYC protein expression by IHC is present in most
      PMBLs. Increased MYC protein expression can be seen in one-third of the cases;
      however, it does not correlate with genetic abnormalities by FISH. There is also
      no significant impact of MYC protein expression on clinical outcomes.

PMID- 25780016
TI  - Correction.
AB  - In the March 2015 AJCP article by the African Strategies for Advancing Pathology
      Group (African Strategies for Advancing Pathology Group Members. Quality
      pathology and laboratory diagnostic services are key to improving global health
      outcomes: improving global health is not possible without accurate disease
      diagnosis. Am J Clin Pathol. 2015;143:325-328), the name of Lorenzo Leoncini,
      Siena, Italy, was inadvertently omitted from the list of members. We apologize
      for this omission.

PMID- 25780017
TI  - Oral Health and Blood Pressure: The IPC Cohort.
AB  - BACKGROUND: Chronic periodontal diseases involve bacteria-induced inflammation of
      the tissues supporting the teeth. An inflammatory origin for hypertension has
      been proposed, and periodontal diseases are associated with an increased risk of
      vascular disease. The present study was performed to assess whether oral health
      conditions were associated with the risk of hypertension in adult population.
      METHODS: The sample comprised 102,330 subjects, who underwent medical and oral
      examinations between 2002 and 2011. A full-mouth clinical examination was
      performed using simplified plaque index, calculus index, and simplified modified
      gingival index to assess dental plaque, dental calculus and gingival
      inflammation. The number of teeth was recorded. Biological parameters, including
      blood pressure were assessed. A subset analysis according to age (<65 or >=65
      years) was conducted. The association between blood pressure and oral conditions
      was explored using a logistic regression approach. RESULTS: In the sample of
      subject >=65 years, no significant association was found between oral variables
      and the risk of hypertension. In subset <65 years, oral variables and risk of
      hypertension were associated. Insufficient masticatory function and missing teeth
      (>10) showed odds ratio (OR) = 1.20 [95% CI = 1.08-1.32] and OR = 1.17 [95% CI =
      1.04-1.31], respectively. Hypertension was also associated with high level of
      dental plaque [OR = 1.90, 95% CI = 1.55-2.33], dental calculus [OR = 1.18, 95% CI
      = 1.07-1.29] and gingival inflammation [OR = 1.56, 95% CI = 1.35-1.80] Moreover,
      in this subset <65 years, the risk of hypertension increases with the number of
      dental exposure. CONCLUSIONS: The present study indicates that insufficient
      masticatory function, poor oral hygiene, and oral inflammation are associated
      with hypertension in subject <65.

PMID- 25780019
TI  - Bronchogenic cyst in left anterior cranial fossa.

PMID- 25780020
TI  - Cefepime-induced jaw myoclonus.

PMID- 25780021
TI  - Palliative care and neurology: time for a paradigm shift.

PMID- 25780022
TI  - Heterogeneity in neurologic education and care in Asian and Oceanian region.

PMID- 25780023
TI  - Postictal nose wiping: a lateralizing sign in temporal lobe complex partial
      seizures.

PMID- 25780024
TI  - Child neurology: Andersen-Tawil syndrome.

PMID- 25780025
TI  - Teaching NeuroImages: Reversible widespread brain MRI lesions in Marchiafava
      Bignami disease.

PMID- 25780026
TI  - Teaching Video NeuroImages: Frontal opercular seizures with jacksonian march.

PMID- 25780027
TI  - Interventions for Increasing Subsequent Alcohol Treatment Utilisation Among
      Patients with Alcohol Use Disorders from Somatic Inpatient Settings: A Systematic
      Review.
AB  - AIMS: Alcohol Use Disorders (AUDs) are common in medical and surgical hospital
      wards. Brief Interventions (BIs) for reducing alcohol use and consequences are
      generally inefficacious in this population. Because there is evidence that
      receipt of formal treatment could be useful, we performed a systematic review to
      determine efficacious interventions for increasing subsequent alcohol treatment
      from these settings. METHODS: A systematic literature search of articles
      published prior to December 2013 to identify articles describing randomised
      controlled trials (RCTs) in three electronic databases: PubMed, PsycINFO and The
      Cochrane Library. Data were extracted independently by one reviewer and were
      checked by a second reviewer. Because of heterogeneity between study groups in
      treatment utilisation during the follow-up, a meta-analysis was considered
      inappropriate and a qualitative synthesis was conducted. RESULTS: From the 5030
      identified records, only 5 RCTs, including 1113 patients with AUDs, met inclusion
      criteria. No evidence of efficacy in increasing subsequent treatment utilisation
      was reported for inpatient BIs alone, but interventions with post-discharge
      sessions might be beneficial. Increased treatment utilisation was generally
      associated with favourable drinking outcomes. CONCLUSIONS: Given the small number
      of included studies and the presence of several alternative methodological
      explanations for the present findings, no firm conclusions could be drawn on
      efficacious interventions for increasing subsequent treatment utilisation among
      somatic inpatients with AUDs. However the findings support efforts to explore
      this under-researched area.

PMID- 25780028
TI  - Consumption of Alcoholic Energy Drinks Is Associated with Work-related Injury or
      Disease Among Manual Workers in Taiwan.
AB  - AIMS: Alcoholic energy drinks (AEDs) have been popular among Taiwanese manual
      workers. Study results concerning increased health risks of AED consumption
      relative to alcohol alone have been inconsistent, and the risk for potential work
      related injury or disease has not been studied. Our study goal was to evaluate
      the association between AED consumption and work-related injury or disease in
      manual workers in Taiwan. METHODS: National survey data of the working population
      in 2007 was utilized. A total of 1192 manual workers, who drank alcohol more than
      once per week, were divided into AED-drinkers and non-AED drinkers. We compared
      AED drinking behaviors and risk of work-related injury or disease between the two
      groups. RESULTS: AED drinkers had a higher risk of work-related injury or
      disease, with an odds ratio of 1.48 (95% CI: 1.14-1.93), after controlling
      demographic, smoking and drinking characteristics. The presence of problem
      drinking (defined by CAGE score equal to or higher than two) was another risk
      factor of having work-related injury or disease. Compared to non-AED
      counterparts, AED drinkers had a significantly higher prevalence of work-related
      injury or disease in the strata of CAGE score of 1 and 2. CONCLUSION: AED
      consumers presented increased risks of work-related injury or disease compared
      with non-AED drinkers among manual workers in Taiwan. In order to conduct an
      effective intervention program to protect Taiwanese manual workers from potential
      risks, the reasons for this increased risk among AED drinkers need to be further
      studied.

PMID- 25780029
TI  - Author response to "Time of day of cognitive tests might distort shift-work study
      results".

PMID- 25780030
TI  - Occupational exposure to N-nitrosamines and pesticides and risk of pancreatic
      cancer.
AB  - OBJECTIVES: Animal evidence shows that N-nitrosamines and similar xenobiotic
      compounds are pancreatic carcinogens. We aimed to determine whether occupational
      exposure to N-nitrosamines or to pesticides increases risk of pancreatic cancer
      development. METHODS: Participants (504 cases, 643 controls) in a population
      based case-control study (The Queensland Pancreatic Cancer Study) provided data
      on demographic, medical and lifestyle factors and lifetime job histories.
      Specific questions were asked regarding work in rubber and leather industries,
      metalworking jobs and occupational or direct use of pesticides on animals or
      crops. An occupational hygienist reviewed this information (blind to case status)
      to assess likelihood of exposure to N-nitrosamines and pesticides, and estimated
      level and frequency of such exposures. RESULTS: No associations were found for
      risk of pancreatic cancer and occupational exposure to N-nitrosamines (OR=0.85,
      95% CI 0.51 to 1.42) and no associations were seen with level or frequency of
      exposure. No associations were observed for ever exposure to pesticides in
      general (OR=0.90, 95% CI 0.61 to 1.33) or to any of the pesticide subgroups.
      Stratification by history of cigarette smoking did not change these results.
      CONCLUSIONS: This comprehensive analysis of a large case-control study does not
      support an association between occupational exposure to N-nitrosamines or
      pesticide use and risk of pancreatic cancer.

PMID- 25780031
TI  - The impact of onsite workplace health-enhancing physical activity interventions
      on worker productivity: a systematic review.
AB  - The aim of this study is to investigate the effects of onsite workplace health
      enhancing physical activity (HEPA) programmes on worker productivity. The
      PROSPERO registration number is CRD42014008750. A search for controlled trials or
      randomised controlled trials (RCTs) that investigated the effects of onsite
      workplace HEPA programmes on productivity levels of working adults was performed.
      Risk of bias of included studies was assessed, and the inter-rater reliability of
      the quality assessment was analysed. Qualitative synthesis of available evidence
      is presented. Eight studies were included in the review. There is consistent
      evidence that onsite workplace HEPA programmes do not reduce levels of sick
      leave. There appears to be inconsistent evidence of the impact of onsite
      workplace HEPA programmes on worker productivity. A high-quality study of an
      onsite combination (aerobic, strengthening and flexibility) HEPA regime and a
      moderate-quality study of a Tai Chi programme improved worker productivity
      measured with questionnaires in female laundry workers and older female nurses,
      respectively. Two high-quality studies and four moderate-quality studies did not
      show benefit. Studies that showed benefit were mainly those designed with
      productivity measures as primary outcomes, delivered to occupations involved with
      higher physical loads, and had higher compliance and programme intensity. The
      small number of studies and the lack of consistency among studies limited further
      analyses. There is inconsistent evidence that onsite workplace HEPA programmes
      improve self-reported worker productivity. Future high-quality RCTs of onsite
      workplace HEPA programmes should be designed around productivity outcomes, target
      at-risk groups and investigate interventions of sufficient intensity. High
      attendance with improved recording is needed to achieve significant results in
      augmenting worker productivity. 

PMID- 25780032
TI  - Occupational asthma after exposure to ortho-phthalaldehyde (OPA).

PMID- 25780033
TI  - Occupational injury risk among ambulance officers and paramedics compared with
      other healthcare workers in Victoria, Australia: analysis of workers'
      compensation claims from 2003 to 2012.
AB  - OBJECTIVE: To investigate occupational risk of musculoskeletal (MSK) and mental
      injury among ambulance officers and paramedics, and compare with nurse
      professionals, social and welfare professionals, and carers and aides in
      Victoria, Australia, using workers' compensation (WC) claims statistics. METHODS:
      Data were retrieved from the Victorian Compensation Research Database (CRD).
      Analysis was restricted to claims received between 1 July 2003 and 30 June 2012.
      WC claim rates were calculated using labour force statistics, and expressed per
      1000 full-time equivalent workers. Adjusted HRs with 95% CIs for injury risk were
      estimated using multivariable regression modelling. RESULTS: Ambulance officers
      and paramedics had an upward trend in WC claim rates for all injuries and the
      highest rates for MSK and mental injury, in comparison with other healthcare
      workers during the study period. In the 2009-2012 time period, ambulance officers
      and paramedics' risk of lower back MSK and mental injury was approximately 13
      times higher than nurse professionals, HRs 57.6 vs 4.4 and 17.77 vs 1.29,
      respectively. Social and welfare professionals had the second highest risk of
      mental injury, which was up to threefold greater than in nurses. Carers and aides
      and nurse professionals had similar HRs overall for all injury categories.
      CONCLUSIONS: Differential patterns of MSK and mental injury exist among
      healthcare occupational groups in Victoria, Australia. Given the significant
      findings, especially the high risks among ambulance personnel, future research
      should focus on the circumstances of injury to improve understanding and inform
      prevention programmes.

PMID- 25780034
TI  - IL-18 acts in synergy with IL-7 to promote ex vivo expansion of T lymphoid
      progenitor cells.
AB  - Although IL-18 has not previously been shown to promote T lymphopoiesis, results
      obtained via a novel data mining algorithm (global microarray meta-analysis) led
      us to explore a predicted role for this cytokine in T cell development. IL-18 is
      a member of the IL-1 cytokine family that has been extensively characterized as a
      mediator of inflammatory immune responses. To assess a potential role for IL-18
      in T cell development, we sort-purified mouse bone marrow-derived common lymphoid
      progenitor cells, early thymic progenitors (ETPs), and double-negative 2
      thymocytes and cultured these populations on OP9-Delta-like 4 stromal layers in
      the presence or absence of IL-18 and/or IL-7. After 1 wk of culture, IL-18
      promoted proliferation and accelerated differentiation of ETPs to the double
      negative 3 stage, similar in efficiency to IL-7. IL-18 showed synergy with IL-7
      and enhanced proliferation of both the thymus-derived progenitor cells and the
      bone marrow-derived common lymphoid progenitor cells. The synergistic effect on
      the ETP population was further characterized and found to correlate with
      increased surface expression of c-Kit and IL-7 receptors on the IL-18-treated
      cells. In summary, we successfully validated the global microarray meta-analysis
      prediction that IL-18 affects T lymphopoiesis and demonstrated that IL-18 can
      positively impact bone marrow lymphopoiesis and T cell development, presumably
      via interaction with the c-Kit and IL-7 signaling axis. 

PMID- 25780035
TI  - Mycobacterium tuberculosis Mce3E suppresses host innate immune responses by
      targeting ERK1/2 signaling.
AB  - Crucial to the pathogenesis of the tuberculosis (TB)-causing pathogen
      Mycobacterium tuberculosis is its ability to subvert host immune defenses to
      promote its intracellular survival. The mammalian cell entry protein 3E (Mce3E),
      located in the region of difference 15 of the M. tuberculosis genome and absent
      in Mycobacterium bovis bacillus Calmette-Guerin, has an essential role in
      facilitating the internalization of mammalian cells by mycobacteria. However,
      relatively little is known about the role of Mce3E in modulation of host innate
      immune responses. In this study, we demonstrate that Mce3E inhibits the
      activation of the ERK1/2 signaling pathway, leading to the suppression of Tnf and
      Il6 expression, and the promotion of mycobacterial survival within macrophages.
      Mce3E interacts and colocalizes with ERK1/2 at the endoplasmic reticulum in a DEF
      motif (an ERK-docking motif)-dependent manner, relocates ERK1/2 from cytoplasm to
      the endoplasmic reticulum, and finally reduces the association of ERK1/2 with
      MEK1 and blocks the nuclear translocation of phospho-ERK1/2. A DEF motif mutant
      form of Mce3E (F294A) loses its ability to suppress Tnf and Il6 expression and to
      promote intracellular survival of mycobacteria. Inhibition of the ERK1/2 pathway
      in macrophages using U0126, a specific inhibitor of the ERK pathway, also leads
      to the suppressed Tnf and Il6 expression and the enhanced intracellular survival
      of mycobacteria. Taken together, these results suggest that M. tuberculosis Mce3E
      exploits the ERK1/2 signaling pathway to suppress host innate immune responses,
      providing a potential Mce3E-ERK1/2 interface-based drug target against M.
      tuberculosis. 

PMID- 25780036
TI  - CD4+ T cell-derived IL-21 and deprivation of CD40 signaling favor the in vivo
      development of granzyme B-expressing regulatory B cells in HIV patients.
AB  - IL-21 can induce both plasma cells and regulatory B cells. In this article, we
      demonstrate that untreated HIV patients display CD4(+) T cells with enhanced IL
      21 expression and high in vivo frequencies of regulatory B cells overexpressing
      the serine protease granzyme B. Granzyme B-expressing regulatory B cells (GraB
      cells) cells from HIV patients exhibit increased expression of CD5, CD43, CD86,
      and CD147 but do not produce IL-10. The main functional characteristic of their
      regulatory activity is direct granzyme B-dependent degradation of the TCR-zeta
      chain, resulting in significantly decreased proliferative T cell responses.
      Although Th cells from HIV patients secrete IL-21 in a Nef-dependent manner, they
      barely express CD40L. When culturing such IL-21(+)CD40L(-) Th cells with B cells,
      the former directly induce B cell differentiation into GraB cells. In contrast,
      the addition of soluble CD40L multimers to T cell/B cell cultures redirects B
      cell differentiation toward plasma cells, indicating that CD40L determines the
      direction of IL-21-dependent B cell differentiation. As proof of principle, we
      confirmed this mechanism in a patient lacking intact CD40 signaling due to a NEMO
      mutation. The majority of peripheral B cells from this patient were GraB cells
      and strongly suppressed T cell proliferation. In conclusion, GraB cells represent
      potent regulatory B cells in humans that are phenotypically and functionally
      distinct from B10 cells and occur in early HIV infection. GraB cells may
      contribute significantly to immune dysfunction in HIV patients, and may also
      explain ineffective Ab responses after vaccination. The use of soluble CD40L
      multimers may help to improve vaccination responses in HIV patients. 

PMID- 25780037
TI  - Minimal sequence requirements for oligodeoxyribonucleotides activating human
      TLR9.
AB  - Synthetic oligodeoxyribonucleotides (ODNs) containing CpG (unmethylated
      deoxycytidylyl-deoxyguanosine dinucleotide) motifs activate endosomal TLR9. The
      nucleotide sequence, length, and dimerization properties of ODNs modulate their
      activation of TLR9. We performed a systematic investigation of the sequence
      motifs of B-class and C-class phosphodiester ODNs to identify the sequence
      properties that govern TLR9 activation. ODNs shorter than 21 nt and with the
      adenosine adjacent to the cytidine-guanosine (CG) dinucleotide motif led to a
      significant loss of the propensity to activate TLR9. The distance between the
      stimulatory CpG motifs within the ODN fine-tunes the activation of B cells. The
      minimal ODNs that activate human TLR9 comprise 2 CG dinucleotides separated by 6
      10 nt, where the first CpG motif is preceded by the 5'-thymidine and the
      elongated poly-thymidine tail at the 3' end of the ODN. The minimal sequence
      provides insight into the molecular mechanism of TLR9 ligand recognition. On the
      basis of sequence requirements, we conclude that two binding sites with different
      affinities for CG are formed in the human TLR9 dimer, with a very stringent
      binding site interacting with the 5' CpG motif. 

PMID- 25780038
TI  - Regulatory T cell-derived adenosine induces dendritic cell migration through the
      Epac-Rap1 pathway.
AB  - Dendritic cells (DC) are one target for immune suppression by regulatory T cells
      (Treg), because their interaction results in reduced T cell stimulatory capacity
      and secretion of inhibitory cytokines in DC. We show that DC in the presence of
      Treg are more mobile as compared with cocultures with conventional CD4(+) T cells
      and form DC-Treg aggregates within 2 h of culture. The migration of DC was
      specifically directed toward Treg, as Treg, but not CD4(+) T cells, attracted DC
      in Boyden chambers. Treg deficient for the ectonucleotidase CD39 were unable to
      attract DC. Likewise, addition of antagonists for A2A adenosine receptors
      abolished the formation of DC-Treg clusters, indicating a role for adenosine in
      guiding DC-Treg interactions. Analysis of the signal transduction events in DC
      after contact to Treg revealed increased levels of cAMP, followed by activation
      of Epac1 and the GTPase Rap1. Subsequently activated Rap1 localized to the
      subcortical actin cytoskeleton in DC, providing a means by which directed
      locomotion of DC toward Treg is facilitated. In aggregate, these data show that
      Treg degrade ATP to adenosine via CD39, attracting DC by activating Epac1-Rap1
      dependent pathways. As a consequence, DC-Treg clusters are formed and DC are
      rendered less stimulatory. This adenosine-mediated attraction of DC may therefore
      act as one mechanism by which Treg regulate the induction of immune responses by
      DC. 

PMID- 25780039
TI  - A role for APPL1 in TLR3/4-dependent TBK1 and IKKepsilon activation in
      macrophages.
AB  - Endosomes have important roles in intracellular signal transduction as a sorting
      platform. Signaling cascades from TLR engagement to IRF3-dependent gene
      transcription rely on endosomes, yet the proteins that specifically recruit IRF3
      activating molecules to them are poorly defined. We show that adaptor protein
      containing a pleckstrin-homology domain, a phosphotyrosine-binding domain, and a
      leucine zipper motif (APPL)1, an early endosomal protein, is required for both
      TRIF- and retinoic acid-inducible gene 1-dependent signaling cascades to induce
      IRF3 activation. APPL1, but not early endosome Ag 1, deficiency impairs IRF3
      target gene expression upon engagement of both TLR3 and TLR4 pathways, as well as
      in H1N1-infected macrophages. The IRF3-phosphorylating kinases TBK1 and
      IKKepsilon are recruited to APPL1 endosomes in LPS-stimulated macrophages.
      Interestingly, APPL1 undergoes proteasome-mediated degradation through ERK1/2 to
      turn off signaling. APPL1 degradation is blocked when signaling through the
      endosome is inhibited by chloroquine or dynasore. Therefore, APPL1 endosomes are
      critical for IRF3-dependent gene expression in response to some viral and
      bacterial infections in macrophages. Those signaling pathways involve the signal
      induced degradation of APPL1 to prevent aberrant IRF3-dependent gene expression
      linked to immune diseases. 

PMID- 25780040
TI  - The upregulation of LAG-3 on T cells defines a subpopulation with functional
      exhaustion and correlates with disease progression in HIV-infected subjects.
AB  - T cells develop functional defects during HIV-1 infection, partially due to the
      upregulation of inhibitory receptors such as programmed death-1 (PD-1) and CTLA
      4. However, the role of lymphocyte activation gene-3 (LAG-3; CD223), also known
      as an inhibitory receptor, in HIV infection remains to be determined. In this
      study, we revealed that LAG-3 on T cells delivers an inhibitory signal to
      downregulate T cell functionality, thereby playing an immunoregulatory role
      during persistent HIV-1 infection. We observed that HIV-1 infection results in a
      significant increase in LAG-3 expression in both the peripheral blood and the
      lymph nodes. The upregulation of LAG-3 is dramatically manifested on both CD4(+)
      and CD8(+) T cells and is correlated with disease progression. As expected,
      prolonged antiretroviral therapy reduces the expression of LAG-3 on both CD4(+)
      and CD8(+) T cells. The ex vivo blockade of LAG-3 significantly augments HIV
      specific CD4(+) and CD8(+) T cell responses, whereas the overexpression of LAG-3
      in T cells or the stimulation of LAG-3 on T cells leads to the reduction of T
      cell responses. Furthermore, most LAG-3 and PD-1 are expressed in different T
      cell subsets. Taken together, these data demonstrate that the LAG-3/MHC class II
      pathway plays an immunoregulatory role, thereby providing an important target for
      enhancing immune reconstitution in HIV-infected patients. Additionally, the LAG
      3/MHC class II pathway may synergize with PD-1/PD ligand to enhance T cell
      mediated immune responses. 

PMID- 25780041
TI  - Distinct modes of antigen presentation promote the formation, differentiation,
      and activity of foxp3+ regulatory T cells in vivo.
AB  - How the formation and activity of CD4(+)Foxp3(+) regulatory T cells (Tregs) are
      shaped by TCR recognition of the diverse array of peptide:MHC complexes that can
      be generated from self-antigens and/or foreign Ags in vivo remains poorly
      understood. We show that a self-peptide with low (but not high) stimulatory
      potency promotes thymic Treg formation and can induce conventional CD4(+) T cells
      in the periphery to become Tregs that express different levels of the
      transcription factor Helios according to anatomical location. When Tregs
      generated in response to this self-peptide subsequently encountered the same
      peptide derived instead from influenza virus in the lung-draining lymph nodes of
      infected mice, they proliferated, acquired a T-bet(+)CXCR3(+) phenotype, and
      suppressed the antiviral effector T cell response in the lungs. However, these
      self-antigen-selected Tregs were unable to suppress the antiviral immune response
      based on recognition of the peptide as a self-antigen rather than a viral Ag.
      Notably, when expressed in a more immunostimulatory form, the self-peptide
      inhibited the formation of T-bet(+)CXCR3(+) Tregs in response to viral Ag, and Ag
      expressing B cells from these mice induced Treg division without upregulation of
      CXCR3. These studies show that a weakly immunostimulatory self-peptide can induce
      thymic and peripheral Foxp3(+) Treg formation but is unable to activate self
      antigen-selected Tregs to modulate an antiviral immune response. Moreover, a
      strongly immunostimulatory self-peptide expressed by B cells induced Tregs to
      proliferate without acquiring an effector phenotype that allows trafficking from
      the draining lymph node to the lungs and, thereby, prevented the Tregs from
      suppressing the antiviral immune response. 

PMID- 25780042
TI  - IL-10/HMOX1 signaling modulates cochlear inflammation via negative regulation of
      MCP-1/CCL2 expression in cochlear fibrocytes.
AB  - Cochlear inflammatory diseases, such as tympanogenic labyrinthitis, are
      associated with acquired sensorineural hearing loss. Although otitis media is
      extremely frequent in children, tympanogenic labyrinthitis is not commonly
      observed, which suggests the existence of a potent anti-inflammatory mechanism
      modulating cochlear inflammation. In this study, we aimed to determine the
      molecular mechanism involved in cochlear protection from inflammation-mediated
      tissue damage, focusing on IL-10 and hemoxygenase-1 (HMOX1) signaling. We
      demonstrated that IL-10Rs are expressed in the cochlear lateral wall of mice and
      rats, particularly in the spiral ligament fibrocytes (SLFs). The rat SLF cell
      line was found to inhibit nontypeable Haemophilus influenzae (NTHi)-induced
      upregulation of monocyte chemotactic protein-1 (MCP-1; CCL2) in response to IL
      10. This inhibition was suppressed by silencing IL-10R1 and was mimicked by
      cobalt Protoporphyrin IX and CO-releasing molecule-2. In addition, IL-10 appeared
      to suppress monocyte recruitment through reduction of NTHi-induced rat SLF cell
      line-derived chemoattractants. Silencing of HMOX1 was found to attenuate the
      inhibitory effect of IL-10 on NTHi-induced MCP-1/CCL2 upregulation. Chromatin
      immunoprecipitation assays showed that IL-10 inhibits NTHi-induced binding of p65
      NF-kappaB to the distal motif in the promoter region of MCP-1/CCL2, resulting in
      suppression of NTHi-induced NF-kappaB activation. Furthermore, IL-10 deficiency
      appeared to significantly affect cochlear inflammation induced by intratympanic
      injections of NTHi. Taken together, our results suggest that IL-10/HMOX1
      signaling is involved in modulation of cochlear inflammation through inhibition
      of MCP-1/CCL2 regulation in SLFs, implying a therapeutic potential for a CO-based
      approach for inflammation-associated cochlear diseases. 

PMID- 25780043
TI  - IL-17A, but not IL-17F, is indispensable for airway vascular remodeling induced
      by exaggerated Th17 cell responses in prolonged ovalbumin-challenged mice.
AB  - We previously demonstrated an essential role of Th17 cells in excessive mucous
      secretion and airway smooth muscle proliferation in a prolonged OVA-challenged
      C57BL/6 mouse model. However, the impact of Th17 cells in vascular remodeling,
      another characteristic feature of airway remodeling in asthma, remains elusive.
      This issue was further investigated in this study. The time-course experiments
      showed that progressively increasing levels of Th17 cells and IL-17A (not IL-17F)
      in the lungs of prolonged allergen-challenged mice were positively correlated
      with microvessel density in peribronchial tissues. In addition, exaggerated
      airway vascular remodeling in this mouse model was exacerbated by airway
      administration of IL-17A or adoptive transfer of Th17 cells. This effect was
      dramatically alleviated by the administration of anti-IL-17A Ab, but not anti-IL
      17F Ab. Boyden chamber assays indicated that IL-17A accelerates endothelial
      progenitor cell (EPC) migration. Furthermore, EPC accumulation in the airways of
      allergen-exposed mice after adoptive transfer of Th17 cells was eliminated by
      blockade of IL-17A. We found that IL-17A promoted tubule-like formation rather
      than proliferation of pulmonary microvascular endothelia cells (PMVECs) in vitro.
      In addition, IL-17A induced PMVEC tube formation via the PI3K/AKT1 pathway, and
      suppression of the PI3K pathway markedly reduced the formation of tubule-like
      structures. Collectively, our results indicate that Th17 cells contribute to the
      airway vascular remodeling in asthma by mediating EPC chemotaxis, as well as
      PMVEC tube formation, via IL-17A rather than IL-17F. 

PMID- 25780045
TI  - Unique roles of infiltrating myeloid cells in the murine uterus during early to
      midpregnancy.
AB  - Leukocyte infiltration into the uterus is a characteristic feature in early to
      midpregnancy, but the composition and function of these leukocytes are not well
      understood. Using a pregnant murine model, we showed that myeloid cells and
      uterine NK (uNK) cells were the predominant populations in uteri during early to
      midgestation, whereas T and B cells were constrained. Uterine myeloid populations
      included cells that infiltrated from the circulation (myeloid-derived suppressor
      cells [MDSCs], monocyte-derived macrophages [Mphis], and dendritic cells [DCs])
      or proliferated from resident precursors (resident Mphis [Re-Mphis] and DCs).
      CD11b(hi)Ly6-G(hi) cells, representing neutrophils in both blood and uterine
      MDSCs, significantly increased from embryonic days 8.5 to 9.5. To understand
      their putative functions, we used anti-Gr-1 Ab to deplete circulating neutrophils
      and uterine MDSCs. In the absence of MDSC suppression, uterine DCs, T cells, and
      regulatory T cells expanded. Conversely, uterine MDSCs responded to LPS-induced
      inflammation and transformed into CD14(+)-activated neutrophils, resulting in an
      upregulation of tolerogenic DCs. A high dose of LPS (2.5 MUg/mouse) significantly
      increased the influx of neutrophils and production of proinflammatory cytokines,
      such as IL-1beta and TNF-alpha, resulting in the reduction of Re-Mphis and uNK
      cells, and led to placental hemorrhages and fetal deaths. In summary, uterine
      MDSCs are important in early to midpregnancy by responding to the maternal
      immunologic milieu and protecting uNK cells and Re-Mphis via MDSC's suppressive
      and anti-inflammatory functions. Upsetting this delicate immune balance by
      factors leading to either insufficient MDSCs or excessive neutrophil infiltration
      in the fetomaternal interface may contribute to pregnancy failure. 

PMID- 25780044
TI  - Fasciola hepatica fatty acid binding protein inhibits TLR4 activation and
      suppresses the inflammatory cytokines induced by lipopolysaccharide in vitro and
      in vivo.
AB  - TLR4, the innate immunity receptor for bacterial endotoxins, plays a pivotal role
      in the induction of inflammatory responses. There is a need to develop molecules
      that block either activation through TLR4 or the downstream signaling pathways to
      inhibit the storm of inflammation typically elicited by bacterial LPS, which is a
      major cause of the high mortality associated with bacterial sepsis. We report in
      this article that a single i.p. injection of 15 MUg fatty acid binding protein
      from Fasciola hepatica (Fh12) 1 h before exposure to LPS suppressed significantly
      the expression of serum inflammatory cytokines in a model of septic shock using
      C57BL/6 mice. Because macrophages are a good source of IL-12p70 and TNF-alpha,
      and are critical in driving adaptive immunity, we investigated the effect of Fh12
      on the function of mouse bone marrow-derived macrophages (bmMPhis). Although Fh12
      alone did not induce cytokine expression, it significantly suppressed the
      expression of IL-12, TNF-alpha, IL-6, and IL-1beta cytokines, as well as
      inducible NO synthase-2 in bmMPhis, and also impaired the phagocytic capacity of
      bmMPhis. Fh12 had a limited effect on the expression of inflammatory cytokines
      induced in response to other TLR ligands. One mechanism used by Fh12 to exert its
      anti-inflammatory effect is binding to the CD14 coreceptor. Moreover, it
      suppresses phosphorylation of ERK, p38, and JNK. The potent anti-inflammatory
      properties of Fh12 demonstrated in this study open doors to further studies
      directed at exploring the potential of this molecule as a new class of drug
      against septic shock or other inflammatory diseases. 

PMID- 25780046
TI  - Collaborative interactions between type 2 innate lymphoid cells and antigen
      specific CD4+ Th2 cells exacerbate murine allergic airway diseases with prominent
      eosinophilia.
AB  - Type-2 innate lymphoid cells (ILC2s) and the acquired CD4(+) Th2 and Th17 cells
      contribute to the pathogenesis of experimental asthma; however, their roles in Ag
      driven exacerbation of chronic murine allergic airway diseases remain elusive. In
      this study, we report that repeated intranasal rechallenges with only OVA Ag were
      sufficient to trigger airway hyperresponsiveness, prominent eosinophilic
      inflammation, and significantly increased serum OVA-specific IgG1 and IgE in
      rested mice that previously developed murine allergic airway diseases. The recall
      response to repeated OVA inoculation preferentially triggered a further increase
      of lung OVA-specific CD4(+) Th2 cells, whereas CD4(+) Th17 and ILC2 cell numbers
      remained constant. Furthermore, the acquired CD4(+) Th17 cells in Stat6(-/-)/IL
      17-GFP mice, or innate ILC2s in CD4(+) T cell-ablated mice, failed to mount an
      allergic recall response to OVA Ag. After repeated OVA rechallenge or CD4(+) T
      cell ablation, the increase or loss of CD4(+) Th2 cells resulted in an enhanced
      or reduced IL-13 production by lung ILC2s in response to IL-25 and IL-33
      stimulation, respectively. In return, ILC2s enhanced Ag-mediated proliferation of
      cocultured CD4(+) Th2 cells and their cytokine production, and promoted
      eosinophilic airway inflammation and goblet cell hyperplasia driven by adoptively
      transferred Ag-specific CD4(+) Th2 cells. Thus, these results suggest that an
      allergic recall response to recurring Ag exposures preferentially triggers an
      increase of Ag-specific CD4(+) Th2 cells, which facilitates the collaborative
      interactions between acquired CD4(+) Th2 cells and innate ILC2s to drive the
      exacerbation of a murine allergic airway diseases with an eosinophilic phenotype.

PMID- 25780047
TI  - Estimated cost of universal public coverage of prescription drugs in Canada.
AB  - BACKGROUND: With the exception of Canada, all countries with universal health
      insurance systems provide universal coverage of prescription drugs. Progress
      toward universal public drug coverage in Canada has been slow, in part because of
      concerns about the potential costs. We sought to estimate the cost of
      implementing universal public coverage of prescription drugs in Canada. METHODS:
      We used published data on prescribing patterns and costs by drug type, as well as
      source of funding (i.e., private drug plans, public drug plans and out-of-pocket
      expenses), in each province to estimate the cost of universal public coverage of
      prescription drugs from the perspectives of government, private payers and
      society as a whole. We estimated the cost of universal public drug coverage based
      on its anticipated effects on the volume of prescriptions filled, products
      selected and prices paid. We selected these parameters based on current policies
      and practices seen either in a Canadian province or in an international
      comparator. RESULTS: Universal public drug coverage would reduce total spending
      on prescription drugs in Canada by $7.3 billion (worst-case scenario $4.2
      billion, best-case scenario $9.4 billion). The private sector would save $8.2
      billion (worst-case scenario $6.6 billion, best-case scenario $9.6 billion),
      whereas costs to government would increase by about $1.0 billion (worst-case
      scenario $5.4 billion net increase, best-case scenario $2.9 billion net savings).
      Most of the projected increase in government costs would arise from a small
      number of drug classes. INTERPRETATION: The long-term barrier to the
      implementation of universal pharmacare owing to its perceived costs appears to be
      unjustified. Universal public drug coverage would likely yield substantial
      savings to the private sector with comparatively little increase in costs to
      government.

PMID- 25780050
TI  - Drugged driving: how much is too much?

PMID- 25780051
TI  - Federal report calls for regulation of e-cigarettes.

PMID- 25780052
TI  - A false dichotomy.

PMID- 25780053
TI  - Methotrexate-induced nodulosis.

PMID- 25780054
TI  - Google proposes evidence-based search rankings.

PMID- 25780055
TI  - Canada has 1838 drinking-water advisories.

PMID- 25780056
TI  - Doctors v. government: taking the fight online.

PMID- 25780058
TI  - Network-based identification of feedback modules that control RhoA activity and
      cell migration.
AB  - Cancer cell migration enables metastatic spread causing most cancer deaths. Rho
      family GTPases control cell migration, but being embedded in a highly
      interconnected feedback network, the control of their dynamical behavior during
      cell migration remains elusive. To address this question, we reconstructed the
      Rho-family GTPases signaling network involved in cell migration, and developed a
      Boolean network model to analyze the different states and emergent rewiring of
      the Rho-family GTPases signaling network at protrusions and during extracellular
      matrix-dependent cell migration. Extensive simulations and experimental
      validations revealed that the bursts of RhoA activity induced at protrusions by
      EGF are regulated by a negative-feedback module composed of Src, FAK, and CSK.
      Interestingly, perturbing this module interfered with cyclic Rho activation and
      extracellular matrix-dependent migration, suggesting that CSK inhibition can be a
      novel and effective intervention strategy for blocking extracellular matrix
      dependent cancer cell migration, while Src inhibition might fail, depending on
      the genetic background of cells. Thus, this study provides new insights into the
      mechanisms that regulate the intricate activation states of Rho-family GTPases
      during extracellular matrix-dependent migration, revealing potential new targets
      for interfering with extracellular matrix-dependent cancer cell migration. 

PMID- 25780057
TI  - Increased monocyte turnover is associated with interstitial macrophage
      accumulation and pulmonary tissue damage in SIV-infected rhesus macaques.
AB  - We recently reported that increasing blood monocyte turnover that was associated
      with tissue macrophage death better predicts terminal disease progression in
      adult SIV-infected macaques than does declining CD4(+) T cell levels. To
      understand better mechanisms of pathogenesis, this study relates severity of lung
      tissue damage to the ratio, distribution, and inflammatory responses of lung
      macrophage subsets during SIV infection in rhesus macaques exhibiting varying
      rates of monocyte turnover. In vivo BrdU incorporation was used to evaluate
      kinetics of monocyte/tissue macrophage turnover. Tissue damage was scored
      microscopically from H&E-stained lung-tissue sections, and cytokine expression
      was examined via immunohistochemistry and confocal microscopy. Increased monocyte
      turnover in SIV-infected rhesus macaques significantly correlated with severity
      of lung-tissue damage, as exhibited by perivasculitis, vasculitis, interstitial
      pneumonia, alveolar histiocytosis, foamy macrophages, multinucleated giant cells,
      fibrin, and edema in the alveoli. In addition, the higher monocyte turnover
      correlated with declining AI ratio, increased accumulation of IM in the
      perivascular region of the lung, and higher expression of IL-6 in the IM of the
      lung tissue exposed to a LPS, calcium ionophore, and tumor promoter combination
      stimulation ex vivo. Accumulation of IM associated with increasing monocyte
      turnover during SIV infection appears to contribute to chronic pulmonary
      inflammation and tissue damage during disease progression to AIDS. 

PMID- 25780060
TI  - Acute Toxicity From Breast Cancer Radiation Using Helical Tomotherapy With a
      Simultaneous Integrated Boost.
AB  - PURPOSE: To evaluate 2 simultaneous integrated boost treatment planning
      techniques using helical tomotherapy for breast conserving therapy with regard to
      acute skin toxicity and dosimetry. METHODS: Thirty-two patients were studied. The
      original approach was for 16 patients and incorporated a directional block of the
      ipsilateral lung and breast. An additional 16 patients were planned for using a
      modified approach that incorporates a full block of the ipsilateral lung
      exclusive of 4 cm around the breast. Dose-volume histograms of targets and
      critical structures were evaluated. Skin toxicity monitoring was performed
      throughout treatment and follow-up using the Common Terminology Criteria for
      Adverse Events. RESULTS: Treatment was well tolerated with patients receiving a
      median dose of 59.36 Gy. Of the 16 patients in both groups, 8 had grade 2
      erythema immediately after radiation. On 3-week follow-up, 10 and 7 patients in
      the original and modified groups showed grade 1 erythema. On 3- and 6-month
      follow-up, both groups had minimal erythema, with all patients having either
      grade 0 or 1 symptoms. No grade 2 or 3 toxicities were reported. Mean treatment
      time was 7.5 and 10.4 minutes using the original and modified methods. Adequate
      dose coverage was achieved using both methods (V95 = 99.5% and 98%). Mean dose to
      the heart was 10.5 and 1.8 Gy, respectively (P < .01). For right-sided tumors,
      the original and modified plans yielded a mean of 8.8 and 1.1 Gy (P < .01) versus
      11.7 and 2.4 Gy for left-sided tumors (P < .01). The mean dose to the ipsilateral
      lung was also significantly lower in the modified plans (11.8 vs. 5.0 Gy, P <
      .01). CONCLUSIONS: Tomotherapy is capable of delivering homogeneous treatment
      plans to the whole breast and lumpectomy cavity using simultaneous integrated
      boost treatment. Using the treatment methods described herein, extremely low
      doses to critical structures can be achieved without compromising acute skin
      toxicity.

PMID- 25780059
TI  - Roles of collecting duct renin and (pro)renin receptor in hypertension: mini
      review.
AB  - In angiotensin (Ang)-II-dependent hypertension, collecting duct renin synthesis
      and secretion are stimulated despite suppression of juxtaglomerular (JG) renin.
      This effect is mediated by Ang II type 1 (AT1) receptor independent of blood
      pressure. Although the regulation of JG renin is known, the mechanisms by which
      renin is regulated in the collecting duct are not completely understood. The
      presence of renin activity in the collecting duct may provide a pathway for
      intratubular Ang II formation since angiotensinogen substrate and angiotensin
      converting enzyme are present in the distal nephron. The recently named new
      member of the renin-angiotensin system (RAS), the (pro)renin receptor [(P)RR], is
      able to bind renin and the inactive prorenin, thus enhancing renin activity and
      fully activating prorenin. We have demonstrated that renin and (P)RR are
      augmented in renal tissues from rats infused with Ang II and during sodium
      depletion, suggesting a physiological role in intrarenal RAS activation.
      Importantly, (P)RR activation also causes activation of intracellular pathways
      associated with increased cyclooxygenase 2 expression and induction of
      profibrotic genes. In addition, renin and (P)RR are upregulated by Ang II in
      collecting duct cells. Although the mechanisms involved in their regulation are
      still under study, they seem to be dependent on the intrarenal RAS activation.
      The complexities of the mechanisms of stimulation also depend on cyclooxygenase 2
      and sodium depletion. Our data suggest that renin and (P)RR can interact to
      increase intratubular Ang II formation and the activation of profibrotic genes in
      renal collecting duct cells. Both pathways may have a critical role in the
      development of hypertension and renal disease. 

PMID- 25780061
TI  - Perceptions of options available for victims of physical intimate partner
      violence in northern India.
AB  - We used qualitative methodologies to understand perceptions regarding options
      available for victims of physical intimate partner violence (IPV) in northern
      India. We interviewed male and female community members along with IPV experts.
      Interviews were transcribed, coded, and analyzed using grounded theory.
      Participants emphasized that a victim of physical IPV should bear the violence,
      modify her husband's behaviors, or seek help from her natal family. Accessing
      external resources such as the police or nongovernmental organizations was viewed
      as both socially inappropriate and infeasible. These results have widespread
      implications and lay the foundation for the development of IPV prevention
      initiatives in India.

PMID- 25780062
TI  - Modulation of murine breast tumor vascularity, hypoxia and chemotherapeutic
      response by exercise.
AB  - Exercise has been shown to improve postischemia perfusion of normal tissues; we
      investigated whether these effects extend to solid tumors. Estrogen receptor
      negative (ER-, 4T1) and ER+ (E0771) tumor cells were implanted orthotopically
      into syngeneic mice (BALB/c, N = 11-12 per group) randomly assigned to exercise
      or sedentary control. Tumor growth, perfusion, hypoxia, and components of the
      angiogenic and apoptotic cascades were assessed by MRI, immunohistochemistry,
      western blotting, and quantitative polymerase chain reaction and analyzed with
      one-way and repeated measures analysis of variance and linear regression. All
      statistical tests were two-sided. Exercise statistically significantly reduced
      tumor growth and was associated with a 1.4-fold increase in apoptosis (sedentary
      vs exercise: 1544 cells/mm(2), 95% CI = 1223 to 1865 vs 2168 cells/mm(2), 95% CI
      = 1620 to 2717; P = .048), increased microvessel density (P = .004), vessel
      maturity (P = .006) and perfusion, and reduced intratumoral hypoxia (P = .012),
      compared with sedentary controls. We also tested whether exercise could improve
      chemotherapy (cyclophosphamide) efficacy. Exercise plus chemotherapy prolonged
      growth delay compared with chemotherapy alone (P < .001) in the orthotopic 4T1
      model (n = 17 per group). Exercise is a potential novel adjuvant treatment of
      breast cancer. 

PMID- 25780063
TI  - Cube search, revisited.
AB  - Observers can quickly search among shaded cubes for one lit from a unique
      direction. However, replace the cubes with similar 2-D patterns that do not
      appear to have a 3-D shape, and search difficulty increases. These results have
      challenged models of visual search and attention. We demonstrate that cube search
      displays differ from those with "equivalent" 2-D search items in terms of the
      informativeness of fairly low-level image statistics. This informativeness
      predicts peripheral discriminability of target-present from target-absent
      patches, which in turn predicts visual search performance, across a wide range of
      conditions. Comparing model performance on a number of classic search tasks, cube
      search does not appear unexpectedly easy. Easy cube search, per se, does not
      provide evidence for preattentive computation of 3-D scene properties. However,
      search asymmetries derived from rotating and/or flipping the cube search displays
      cannot be explained by the information in our current set of image statistics.
      This may merely suggest a need to modify the model's set of 2-D image statistics.
      Alternatively, it may be difficult cube search that provides evidence for
      preattentive computation of 3-D scene properties. By attributing 2-D luminance
      variations to a shaded 3-D shape, 3-D scene understanding may slow search for 2-D
      features of the target. 

PMID- 25780064
TI  - Trajectories and outcomes among children with special health care needs.
AB  - BACKGROUND AND OBJECTIVE: Outcomes for children with special health care needs
      (SHCN) can vary by their patterns and persistence over time. We aimed to
      empirically establish typical SHCN trajectories throughout childhood and their
      predictive relationships with child and parent outcomes. METHODS: The 2 cohorts
      of the nationally representative Longitudinal Study of Australian Children were
      recruited in 2004 at ages 0 to 1 (n = 5107, B cohort) and 4 to 5 years (n = 4983,
      K cohort). The parent-reported Children With SHCN Screener (Short Form) was
      completed at each of 4 biennial waves. Wave 4 outcomes were parent-reported
      behavior and health-related quality of life, teacher-reported learning, and
      directly assessed cognition. Both parents self-reported mental distress. We
      derived intracohort trajectories by using latent class analysis in Mplus. We
      compared mean outcome scores across trajectories by using linear regression,
      adjusting for socioeconomic position. RESULTS: Four distinct SHCN trajectories
      were replicated in both cohorts: persistent (B 6.8%, K 8.7%), emerging (B 4.1%, K
      11.5%), transient (B 7.9%, K 4.2%), and none (B 81.3%, K 75.6%). Every outcome
      was adversely affected except fathers' mental health. From infancy to age 6 to 7
      years, the persistent and emerging groups had similarly poor outcomes. From age 4
      and 5 to 10 and 11 years, outcomes were incrementally poorer on moving from none
      to transient to emerging and to persistent SHCN. Effect sizes were largest for
      behavior, learning, and psychosocial outcomes. CONCLUSIONS: Adverse outcomes are
      shaped more by cumulative burden than point prevalence of SHCNs. In addition to
      providing care according to a child's need at any given time, prioritizing care
      toward persistent SHCNs may have the biggest benefits for children and parents.

PMID- 25780065
TI  - Children with special health care needs: with population-based data, better
      individual care plans.

PMID- 25780066
TI  - Delayed-onset of multiple cutaneous infantile hemangiomas due to propranolol: a
      case report.
AB  - Infantile hemangiomas are the most common vascular tumors in childhood. In view
      of its proven effectiveness in such cases, propranolol is the drug of choice. We
      present the case of a male infant who started treatment with propranolol shortly
      after birth due to heart disease. After 7 months, when the patient had suffered
      various respiratory exacerbations, this treatment was suspended. One week later,
      multiple skin lesions (ie, multifocal infantile hemangiomas) began to appear,
      with no extracutaneous involvement. It was decided to resume treatment with
      propranolol, although at lower doses than before, and the skin lesions improved
      rapidly, with some disappearing completely. Treatment was definitively withdrawn
      at age 16 months, with only slight recurrence of the lesions. The case described
      is of multifocal infantile hemangiomas without extracutaneous involvement
      appearing beyond the neonatal period after treatment with propranolol beginning
      in the first days of life. The details of the case support the hypothesis that
      this drug is not only therapeutic but also plays a prophylactic role against
      infantile hemangiomas. In turn, this supports the recent proposal that this drug
      may be useful in preventing the growth and spread of tumors with high angiogenic
      potential. It is postulated that the inhibition of beta-adrenergic receptors is
      associated with multiple intracellular processes related to the progression and
      metastasis of different tumors. 

PMID- 25780067
TI  - Isolated linear skull fractures in children with blunt head trauma.
AB  - BACKGROUND AND OBJECTIVE: Children and adolescents with minor blunt head trauma
      and isolated skull fractures are often admitted to the hospital. The objective of
      this study was to describe the injury circumstances and frequency of clinically
      important neurologic complications among children with minor blunt head trauma
      and isolated linear skull fractures. METHODS: This study was a planned secondary
      analysis of a large prospective cohort study in children <18 years old with blunt
      head trauma. Data were collected in 25 emergency departments. We analyzed
      patients with Glasgow Coma Scale scores of 14 or 15 and isolated linear skull
      fractures. We ascertained acute neurologic outcomes through clinical information
      collected during admission or via telephone or mail at least 1 week after the
      emergency department visit. RESULTS: In the parent study, we enrolled 43,904
      children (11,035 [25%] <2 years old). Of those with imaging studies, 350 had
      isolated linear skull fractures. Falls were the most common injury mechanism,
      accounting for 70% (81% for ages <2 years old). Of 201 hospitalized children, 42
      had computed tomography or MRI repeated; 5 had new findings but none required
      neurosurgical intervention. Of 149 patients discharged from the hospital, 20 had
      repeated imaging, and none had new findings. CONCLUSIONS: Children with minor
      blunt head trauma and isolated linear skull fractures are at very low risk of
      evolving other traumatic findings noted in subsequent imaging studies or
      requiring neurosurgical intervention. Hospital admission for neurologically
      normal children with isolated linear skull fractures after minor blunt head
      trauma for monitoring is typically unnecessary.

PMID- 25780068
TI  - Handheld echocardiography versus auscultation for detection of rheumatic heart
      disease.
AB  - BACKGROUND: Rheumatic heart disease (RHD) remains a major public health concern
      in developing countries, and routine screening has the potential to improve
      outcomes. Standard portable echocardiography (STAND) is far more sensitive than
      auscultation for the detection of RHD but remains cost-prohibitive in resource
      limited settings. Handheld echocardiography (HAND) is a lower-cost alternative.
      The purpose of this study was to assess the incremental value of HAND over
      auscultation to identify RHD. METHODS: RHD screening was completed for
      schoolchildren in Gulu, Uganda, by using STAND performed by experienced
      echocardiographers. Any child with mitral or aortic regurgitation or stenosis
      plus a randomly selected group of children with normal STAND findings underwent
      HAND and auscultation. STAND and HAND studies were interpreted by 6 experienced
      cardiologists using the 2012 World Heart Federation criteria. Sensitivity and
      specificity of HAND and auscultation for the detection of RHD and pathologic
      mitral or aortic regurgitation were calculated by using STAND as the gold
      standard. RESULTS: Of 4773 children who underwent screening with STAND, a
      subgroup of 1317 children underwent HAND and auscultation. Auscultation had
      uniformly poor sensitivity for the detection of RHD or valve disease. Sensitivity
      was significantly improved by using HAND compared with auscultation for the
      detection of definite RHD (97.8% vs 22.2%), borderline or definite RHD (78.4% vs
      16.4%), and pathologic aortic insufficiency (81.8% vs 13.6%). CONCLUSIONS:
      Auscultation alone is a poor screening test for RHD. HAND significantly improves
      detection of RHD and may be a cost-effective screening strategy for RHD in
      resource-limited settings.

PMID- 25780069
TI  - Sociodemographic attributes and spina bifida outcomes.
AB  - BACKGROUND: A National Spina Bifida Patient Registry (NSBPR) was begun in 2009 to
      help understand the natural history of spina bifida (SB) and the effects of
      treatments provided by SB clinics. We used the NSBPR to explore the relationship
      of sociodemographic characteristics with SB outcomes. METHODS: Using NSBPR data
      collected in 2009 to 2012, we examined the unadjusted association between
      demographic characteristics and 4 SB outcomes: bowel continence, bladder
      continence, mobility, and presence of pressure sores. We then developed
      multivariable logistic models to explore these relationships while controlling
      for SB clinic, SB type, and level of lesion. RESULTS: Data were available on 2054
      patients <22 years of age from 10 SB clinics. In the multivariable models, older
      age groups were more likely to have continence and pressure sores and less likely
      to be community ambulatory. Males and patients without private insurance were
      less likely to be continent and community ambulatory. Non-Hispanic blacks were
      less likely to be continent. Level of lesion was associated with all outcomes; SB
      type was associated with all but pressure sores; and all outcomes except
      community ambulation showed significant variation across clinic sites.
      CONCLUSIONS: Sociodemographic attributes are associated with SB outcomes. In
      particular, males, non-Hispanic blacks, and patients without private insurance
      have less favorable outcomes, and age has an impact as well. These
      characteristics need to be considered by clinicians who care for this patient
      population and factored into case-mix adjustment when evaluating variation in
      clinical and functional outcomes among different SB clinics.

PMID- 25780070
TI  - Improvement methodology increases guideline recommended blood cultures in
      children with pneumonia.
AB  - BACKGROUND AND OBJECTIVE: A national evidence-based guideline for the management
      of community-acquired pneumonia (CAP) in children recommends blood cultures for
      patients admitted with moderate to severe illness. Our primary aim was to
      increase ordering of blood cultures for children hospitalized with CAP from 53%
      to 90% in 6 months. The secondary aim was to evaluate the effect of obtaining
      blood cultures on length of stay (LOS). METHODS: At a tertiary children's
      hospital, interventions to increase blood cultures focused on 3 key drivers and
      were tested separately in the emergency department and inpatient units by using
      multiple plan-do-study-act cycles. The impact of the interventions was tracked
      over time on run charts. The association of ordering blood cultures and LOS was
      estimated by using linear regression models. RESULTS: Within 6 months, the
      percentage of patients admitted with CAP who had blood cultures ordered increased
      from 53% to 100%. This change has been sustained for 12 months. Overall, 239
      (79%) of the 303 included patients had a blood culture ordered; of these, 6
      (2.5%) were positive. Patients who had a blood culture did not have an increased
      LOS compared with those without a blood culture. CONCLUSIONS: Quality improvement
      methods were used to increase adherence to evidence-based national guidelines for
      performing blood cultures on children hospitalized with CAP; LOS did not
      increase. These results support obtaining blood cultures on all patients admitted
      with CAP without negative effects on LOS in a setting with a reliably low false
      positive blood culture rate.

PMID- 25780071
TI  - Lung ultrasound for the diagnosis of pneumonia in children: a meta-analysis.
AB  - BACKGROUND AND OBJECTIVE: Pneumonia is the leading cause of death of children.
      Diagnostic tools include chest radiography, but guidelines do not currently
      recommend the use of lung ultrasound (LUS) as a diagnostic method. We conducted a
      meta-analysis to summarize evidence on the diagnostic accuracy of LUS for
      childhood pneumonia. METHODS: We performed a systematic search in PubMed, Embase,
      the Cochrane Library, Scopus, Global Health, World Health Organization-Libraries,
      and Latin American and Caribbean Health Sciences Literature of studies comparing
      LUS diagnostic accuracy against a reference standard. We used a combination of
      controlled key words for age <18 years, pneumonia, and ultrasound. We identified
      1475 studies and selected 15 (1%) for further review. Eight studies (765
      children) were retrieved for analysis, of which 6 (75%) were conducted in the
      general pediatric population and 2 (25%) in neonates. Eligible studies provided
      information to calculate sensitivity, specificity, and positive and negative
      likelihood ratios. Heterogeneity was assessed by using Q and I(2) statistics.
      RESULTS: Five studies (63%) reported using highly skilled sonographers. Overall
      methodologic quality was high, but heterogeneity was observed across studies. LUS
      had a sensitivity of 96% (95% confidence interval [CI]: 94%-97%) and specificity
      of 93% (95% CI: 90%-96%), and positive and negative likelihood ratios were 15.3
      (95% CI: 6.6-35.3) and 0.06 (95% CI: 0.03-0.11), respectively. The area under the
      receiver operating characteristic curve was 0.98. Limitations included the
      following: most studies included in our analysis had a low number of patients,
      and the number of eligible studies was also small. CONCLUSIONS: Current evidence
      supports LUS as an imaging alternative for the diagnosis of childhood pneumonia.
      Recommendations to train pediatricians on LUS for diagnosis of pneumonia may have
      important implications in different clinical settings.

PMID- 25780072
TI  - Are we on the right track? Examining the role of developmental behavioral
      pediatrics.

PMID- 25780073
TI  - Measuring quality of pediatric care: where we've been and where we're going.

PMID- 25780074
TI  - Continuous positive airway pressure with helmet versus mask in infants with
      bronchiolitis: an RCT.
AB  - BACKGROUND: Noninvasive continuous positive airway pressure (CPAP) is usually
      applied with a nasal or facial mask to treat mild acute respiratory failure (ARF)
      in infants. A pediatric helmet has now been introduced in clinical practice to
      deliver CPAP. This study compared treatment failure rates during CPAP delivered
      by helmet or facial mask in infants with respiratory syncytial virus-induced ARF.
      METHODS: In this multicenter randomized controlled trial, 30 infants with
      respiratory syncytial virus-induced ARF were randomized to receive CPAP by helmet
      (n = 17) or facial mask (n = 13). The primary endpoint was treatment failure rate
      (defined as due to intolerance or need for intubation). Secondary outcomes were
      CPAP application time, number of patients requiring sedation, and complications
      with each interface. RESULTS: Compared with the facial mask, CPAP by helmet had a
      lower treatment failure rate due to intolerance (3/17 [17%] vs 7/13 [54%], P =
      .009), and fewer infants required sedation (6/17 [35%] vs 13/13 [100%], P =
      .023); the intubation rates were similar. In successfully treated patients, CPAP
      resulted in better gas exchange and breathing pattern with both interfaces. No
      major complications due to the interfaces occurred, but CPAP by mask had higher
      rates of cutaneous sores and leaks. CONCLUSIONS: These findings confirm that CPAP
      delivered by helmet is better tolerated than CPAP delivered by facial mask and
      requires less sedation. In addition, it is safe to use and free from adverse
      events, even in a prolonged clinical setting.

PMID- 25780075
TI  - State-of-the-art office-based interventions to eliminate youth tobacco use: the
      past decade.
AB  - Tobacco use and tobacco smoke exposure are among the most important preventable
      causes of premature disease, disability, and death and therefore constitute a
      major pediatric health concern. The pediatric primary care setting offers
      excellent opportunities to prevent tobacco use in youth and to deliver cessation
      related treatment to youth and parents who use tobacco. This report updates a
      "state-of-the-art" article published a decade ago on office-based interventions
      to address these issues. Since then there has been marked progress in
      understanding the nature, onset, and trajectories of tobacco use and nicotine
      addiction in youth with implications for clinical practice. In addition,
      clinicians need to remain abreast of emerging nicotine delivery systems, such as
      electronic cigarettes, that may influence uptake or continuation of smoking.
      Although evidence-based practice guidelines for treating nicotine addiction in
      youth are not yet available, research continues to build the evidence base toward
      that goal. In the interim, practical guidelines are available to assist
      clinicians in addressing nicotine addiction in the pediatric clinical setting.
      This article reports current practices in addressing tobacco in pediatric primary
      care settings. It reviews our increasing understanding of youth nicotine
      addiction, summarizes research efforts on intervention in the past decade and
      additional research needed going forward, and provides practical guidelines for
      pediatric health care providers to integrate tobacco use prevention and treatment
      into their clinical practice. Pediatric providers can and should play an
      important role in addressing tobacco use and dependence, both in the youth they
      care for and in parents who use tobacco. 

PMID- 25780076
TI  - Medical providers' understanding of sex trafficking and their experience with at
      risk patients.
AB  - BACKGROUND AND OBJECTIVES: Sex trafficking (ST) victims have unique medical and
      mental health needs and are often difficult to identify. Our objectives were to
      evaluate knowledge gaps and training needs of medical providers, to demonstrate
      the importance of provider training to meet the pediatric ST victim's specific
      needs, and to highlight barriers to the identification of and response to
      victims. METHODS: A survey was sent to providers in specialties that would be
      most likely to encounter victims of ST. Participants included physicians, nurses,
      physician assistants, social workers, and patient and family advocates at
      multiple hospitals and medical clinics in urban, suburban, and rural locations.
      RESULTS: Of ~ 500 survey recipients, 168 participants responded. In 2 clinical
      vignettes, 48% correctly classified a minor as an ST victim, and 42% correctly
      distinguished an ST victim from a child abuse victim. In all, 63% of respondents
      said that they had never received training on how to identify ST victims. Those
      with training were more likely to report ST as a major problem locally (P <=
      .001), to have encountered a victim in their practice (P <= .001), and to have
      greater confidence in their ability to identify victims (P <= .001). The greatest
      barriers to identification of victims reported were a lack of training (34%) and
      awareness (22%) of ST. CONCLUSIONS: Health care providers demonstrate gaps in
      knowledge and awareness of ST, specifically of pediatric victims, that correlate
      with their limited experience and training. Training is crucial to improve
      identification of these victims and provide appropriate care for their specific
      needs.

PMID- 25780077
TI  - 13-valent pneumococcal conjugate vaccine (PCV13) in preterm versus term infants.
AB  - OBJECTIVES: This study evaluated the immune response and safety profile of 13
      valent pneumococcal conjugate vaccine (PCV13) in preterm infants compared with
      term infants. METHODS: This Phase IV, open-label, 2-arm, multicenter, parallel
      group study enrolled 200 healthy infants (preterm, n = 100; term, n = 100) aged
      42 to 98 days. All subjects received PCV13 at ages 2, 3, 4 (infant series), and
      12 (toddler dose [TD]) months, together with routine vaccines (diphtheria-tetanus
      acellular pertussis, hepatitis B, inactivated poliovirus, and Haemophilus
      influenzae type b vaccine and meningococcal group C conjugate vaccine). RESULTS:
      Most subjects achieved an anticapsular immunoglobulin G (IgG) antibody
      concentration >= 0.35 MUg/mL for all serotypes: >85% after the infant series
      (except preterm infants for serotypes 5, 6A, and 6B) and >97% after TD (except
      for serotype 3). Preterm infants had overall lower IgG geometric mean
      concentrations compared with term infants; however, geometric mean fold increases
      after TD were similar for all serotypes. Opsonophagocytic activity results were
      consistent with IgG results and titers increased after TD in both groups for all
      serotypes, including serotype 3. PCV13 was generally well tolerated, with similar
      safety profiles in all preterm subgroups. CONCLUSIONS: Immune responses were
      lower in preterm infants than in term infants. However, the majority of subjects
      in both groups achieved both pneumococcal serotype-specific IgG antibody levels
      after the infant series that exceeded the World Health Organization-established
      threshold of protection and functional antibody responses. Responses were
      uniformly higher after TD, reinforcing the importance of a timely booster dose.
      PCV13 was well tolerated regardless of gestational age.

PMID- 25780079
TI  - Screening for deafness.

PMID- 25780080
TI  - Screening for deafness.

PMID- 25780081
TI  - Residency matching woes.

PMID- 25780082
TI  - A more correct interpretation.

PMID- 25780083
TI  - Obesity solutions?

PMID- 25780084
TI  - Obesity solutions?

PMID- 25780085
TI  - Noninvasive functional and anatomical imaging of the human medial temporal lobe.
AB  - The ability to remember life's events, and to leverage memory to guide behavior,
      defines who we are and is critical for everyday functioning. The neural
      mechanisms supporting such mnemonic experiences are multiprocess and multinetwork
      in nature, which creates challenges for studying them in humans and animals.
      Advances in noninvasive neuroimaging techniques have enabled the investigation of
      how specific neural structures and networks contribute to human memory at its
      many cognitive and mechanistic levels. In this review, we discuss how functional
      and anatomical imaging has provided novel insights into the types of information
      represented in, and the computations performed by, specific medial temporal lobe
      (MTL) regions, and we consider how interactions between the MTL and other
      cortical and subcortical structures influence what we learn and remember. By
      leveraging imaging, researchers have markedly advanced understanding of how the
      MTL subserves declarative memory and enables navigation of our physical and
      mental worlds. 

PMID- 25780086
TI  - Moderate alcohol consumption does not impair overload-induced muscle hypertrophy
      and protein synthesis.
AB  - Chronic alcohol consumption leads to muscle weakness and atrophy in part by
      suppressing protein synthesis and mTORC1-mediated signaling. However, it is
      unknown whether moderate alcohol consumption also prevents overload-induced
      muscle growth and related anabolic signaling. Hypertrophy of the plantaris muscle
      was induced by removal of a section of the gastrocnemius and soleus muscles from
      one leg of C57BL/6 adult male mice while the contralateral leg remained intact as
      the sham control. A nutritionally complete alcohol-containing liquid diet (EtOH)
      or isocaloric, alcohol-free liquid diet (Con) was provided for 14 days post
      surgery. EtOH intake was increased progressively (day 1-5) before being
      maintained at ~20 g/day/kg BW. The plantaris muscle from the sham and OL leg was
      removed after 14 days at which time there was no difference in body weight
      between Con and EtOH-fed mice. OL increased muscle weight (90%) and protein
      synthesis (125%) in both Con and EtOH mice. The overload-induced increase in mTOR
      (Ser2448), 4E-BP1 (Thr37/46), S6K1 (Thr389), rpS6 (Ser240/244), and eEF2 (Thr56)
      were comparable in muscle from Con and EtOH mice. Modulation of signaling
      upstream of mTORC1 including REDD1 protein expression, Akt (Thr308), PRAS40
      (Thr246), and ERK (Thr202/Tyr204) also did not differ between Con and EtOH mice.
      Markers of autophagy (ULK1, p62, and LC3) suggested inhibition of autophagy with
      overload and activation with alcohol feeding. These data show that moderate
      alcohol consumption does not impair muscle growth, and therefore imply that
      resistance exercise may be an effective therapeutic modality for alcoholic
      related muscle disease. 

PMID- 25780087
TI  - Stimulating angiogenesis mitigates the unloading-induced reduction in
      osteogenesis in early-stage bone repair in rats.
AB  - Accelerating fracture healing during bed rest allows early mobilization and
      avoids prolonged fracture healing times. We tested the hypothesis that
      stimulating angiogenesis with deferoxamine (DFO) mitigates the unloading-induced
      reduction in early-stage bone repair. Rats aged 12 weeks were subjected to
      cortical drilling on their tibial diaphysis under anesthesia and treated with
      hindlimb unloading (HU), HU and DFO administration (DFOHU), or weight bearing
      (WB) for 5 or 10 days (HU5/10, DFOHU5/10, WB5/10; n = 8 per groups) until
      sacrifice for vascular casting with a zirconium dioxide-based contrast agent.
      Taking advantage of its absorption discontinuity at the K-absorption edge,
      vascular and bone images in the drill-hole defects were acquired by synchrotron
      radiation subtraction CT. Bone repair was reduced in HU rats. The bone volume
      fraction (B.Vf) was 88% smaller in HU5 and 42% smaller in HU10 than in WB5/10.
      The bone segment densities (B.Seg) were 97% smaller in HU5 and 141% larger in
      HU10 than in WB5/10, and bone thickness (B.Th) was 38% smaller in HU10 than in
      WB10. The vascular volume fraction (V.Vf) was 35% and the mean vessel diameter
      (V.D) was 13% smaller in HU10 than in WB10. When compared according to
      categorized vessel sizes, V.Vf in the diameter ranges 20-30, 30-40, and >40 MUm
      were smaller in HU10 than in WB10, and V.Seg in the diameter range >40 MUm was
      smaller in HU10 than in WB10. In contrast, there was no difference in B.Vf
      between DFOHU5/10 and WB5/10 and in V.Vf between DFOHU10 and WB10, though B.Seg
      remained 86% smaller in DFOHU5 and 94% larger in DFOHU10 than in WB5/10, and B.Th
      and V.D were 23% and 14% lower in DFOHU10 than in WB10. Vessel size-specific V.Vf
      in the diameter ranges 10-20 and 20-30 MUm was larger in DFOHU5 than in HU5. In
      conclusion, the enhanced angiogenic ingrowth mitigates the reduction in bone
      repair during mechanical unloading. 

PMID- 25780088
TI  - Pathological hypertrophy reverses beta2-adrenergic receptor-induced angiogenesis
      in mouse heart.
AB  - beta-adrenergic activation and angiogenesis are pivotal for myocardial function
      but the link between both events remains unclear. The aim of this study was to
      explore the cardiac angiogenesis profile in a mouse model with cardiomyocyte
      restricted overexpression of beta2-adrenoceptors (beta2-TG), and the effect of
      cardiac pressure overload. beta2-TG mice had heightened cardiac angiogenesis,
      which was essential for maintenance of the hypercontractile phenotype seen in
      this model. Relative to controls, cardiomyocytes of beta2-TGs showed upregulated
      expression of vascular endothelial growth factor (VEGF), heightened
      phosphorylation of cAMP-responsive-element-binding protein (CREB), and increased
      recruitment of phospho-CREB, CREB-binding protein (CBP), and p300 to the VEGF
      promoter. However, when hearts were subjected to pressure overload by transverse
      aortic constriction (TAC), angiogenic signaling in beta2-TGs was inhibited within
      1 week after TAC. beta2-TG hearts, but not controls, exposed to pressure overload
      for 1-2 weeks showed significant increases from baseline in phosphorylation of
      Ca(2+)/calmodulin-dependent kinase II (CaMKIIdelta) and protein expression of
      p53, reduction in CREB phosphorylation, and reduced abundance of phospho-CREB,
      p300 and CBP recruited to the CREB-responsive element (CRE) site of VEGF
      promoter. These changes were associated with reduction in both VEGF expression
      and capillary density. While non-TG mice with TAC developed compensatory
      hypertrophy, (2-TGs exhibited exaggerated hypertrophic growth at week-1 post-TAC,
      followed by LV dilatation and reduced fractional shortening measured by serial
      echocardiography. In conclusion, angiogenesis was enhanced by the cardiomyocyte
      (2AR/CREB/VEGF signaling pathway. Pressure overload rapidly inhibited this
      signaling, likely as a consequence of activated CaMKII and p53, leading to
      impaired angiogenesis and functional decompensation. 

PMID- 25780089
TI  - Disturbed shear stress reduces Klf2 expression in arterial-venous fistulae in
      vivo.
AB  - Laminar shear stress (SS) induces an antiproliferative and anti-inflammatory
      endothelial phenotype and increases Klf2 expression. We altered the diameter of
      an arteriovenous fistula (AVF) in the mouse model to determine whether increased
      fistula diameter produces disturbed SS in vivo and if acutely increased disturbed
      SS results in decreased Klf2 expression. The mouse aortocaval fistula model was
      performed with 22, 25, or 28 gauge needles to puncture the aorta and the inferior
      vena cava. Duplex ultrasound was used to examine the AVF and its arterial inflow
      and venous outflow, and SS was calculated. Arterial samples were examined with
      western blot, immunohistochemistry, and immunofluorescence analysis for proteins
      and qPCR for RNA. Mice with larger diameter fistulae had diminished survival but
      increased AVF patency. Increased SS magnitudes and range of frequencies were
      directly proportional to the needle diameter in the arterial limb proximal to the
      fistula but not in the venous limb distal to the fistula, with 22-gauge needles
      producing the most disturbed SS in vivo. Klf2 mRNA and protein expression was
      diminished in the artery proximal to the fistula in proportion to increasing SS.
      Increased fistula diameter produces increased SS magnitude and frequency,
      consistent with disturbed SS in vivo. Disturbed SS is associated with decreased
      mRNA and protein expression of Klf2. Disturbed SS and reduced Klf2 expression
      near the fistula are potential therapeutic targets to improve AVF maturation. 

PMID- 25780090
TI  - Early pulmonary events of nose-only water pipe (shisha) smoking exposure in mice.
AB  - Water pipe smoking (WPS) is increasing in popularity and prevalence worldwide.
      Convincing data suggest that the toxicants in WPS are similar to that of
      cigarette smoke. However, the underlying pathophysiologic mechanisms related to
      the early pulmonary events of WPS exposure are not understood. Here, we evaluated
      the early pulmonary events of nose-only exposure to mainstream WPS generated by
      commercially available honey flavored "moasel" tobacco. BALB/c mice were exposed
      to WPS 30 min/day for 5 days. Control mice were exposed using the same protocol
      to atmospheric air only. We measured airway resistance using forced oscillation
      technique, and pulmonary inflammation was evaluated histopathologically and by
      biochemical analysis of bronchoalveolar lavage (BAL) fluid and lung tissue. Lung
      oxidative stress was evaluated biochemically by measuring the level of reactive
      oxygen species (ROS), lipid peroxidation (LPO), reduced glutathione (GSH),
      catalase, and superoxide dismutase (SOD). Mice exposed to WPS showed a
      significant increase in the number of neutrophils (P < 0.05) and lymphocytes (P <
      0.001). Moreover, total protein (P < 0.05), lactate dehydrogenase (P < 0.005),
      and endothelin (P < 0.05) levels were augmented in bronchoalveolar lavage fluid.
      Tumor necrosis factor alpha (P < 0.005) and interleukin 6 (P < 0.05)
      concentrations were significantly increased in lung following the exposure to
      WPS. Both ROS (P < 0.05) and LPO (P < 0.005) in lung tissue were significantly
      increased, whereas the level and activity of antioxidants including GSH (P <
      0.0001), catalase (P < 0.005), and SOD (P < 0.0001) were significantly decreased
      after WPS exposure, indicating the occurrence of oxidative stress. In contrast,
      airway resistance was not increased in WPS exposure. We conclude that subacute,
      nose-only exposure to WPS causes lung inflammation and oxidative stress without
      affecting pulmonary function suggesting that inflammation and oxidative stress
      are early markers of WPS exposure that precede airway dysfunction. Our data
      provide information on the initial steps involved in the respiratory effects of
      WPS, which constitute the underlying causal chain of reactions leading to the
      long-term effects of WPS. 

PMID- 25780091
TI  - Effect of acute acid-base disturbances on the phosphorylation of phospholipase C
      gamma1 and Erk1/2 in the renal proximal tubule.
AB  - The renal proximal tubule (PT) plays a major role in whole-body pH homeostasis by
      secreting H(+) into the tubule lumen. Previous work demonstrated that PTs respond
      to basolateral changes in [CO2] and [HCO3-] by appropriately altering H(+)
      secretion-responses blocked by the ErbB inhibitor PD168393, or by eliminating
      signaling through AT1 angiotensin receptors. In the present study, we analyze
      phosphorylation of three downstream targets of both ErbBs and AT1: phospholipase
      C-gamma1 (PLC-gamma1), extracellular-regulated kinase 1 (Erk1), and Erk2. We
      expose rabbit PT suspensions for 5 and 20 min to our control (Ctrl) condition (5%
      CO2, 22 mmol/L HCO3-, pH 7.40) or one of several conditions that mimic acid-base
      disturbances. We found that each disturbance produces characteristic
      phosphorylation patterns in the three enzymes. For example, respiratory acidosis
      (elevated [CO2], normal [HCO3-]) at 20 min decreases PLC-gamma1 phosphorylation
      at tyrosine-783 (relative to Ctrl). Metabolic acidosis (normal [CO2], decreased
      [HCO3-]) for 5 min increases Erk1 phosphorylation (p-Erk1) but not p-Erk2,
      whereas metabolic alkalosis (normal [CO2], elevated [HCO3-]) for 5 min decreases
      p-Erk1 and p-Erk2. In the presence of CO2/HCO3-, PD168393 blocks only two of
      eight induced decreases in phosphorylation. In two cases in which disturbances
      have no remarkable effects on phosphorylation, PD168393 unmasks decreases and in
      two others, increases. These drug effects provide insight into the roles of
      PD168393-sensitive kinases. Our results indicate that PLC-gamma1.pY783, p-Erk1,
      and p-Erk2 in the PT change in characteristic ways in response to acute acid-base
      disturbances, and thus presumably contribute to the transduction of acid-base
      signals. 

PMID- 25780092
TI  - Association of the ACTN3 R577X polymorphism with glucose tolerance and gene
      expression of sarcomeric proteins in human skeletal muscle.
AB  - A common polymorphism (R577X) in the alpha-actinin (ACTN) 3 gene, which leads to
      complete deficiency of a functional protein in skeletal muscle, could directly
      influence metabolism in the context of health and disease. Therefore, we tested
      the hypothesis that states of glucose tolerance are associated with the ACTN3
      R577X genotype. We analyzed the prevalence of the ACTN3 R577X polymorphism in
      people with normal glucose tolerance (NGT) and type 2 diabetes (T2D) and measured
      muscle-specific alpha-actinin 2 and 3 mRNA and protein abundance in skeletal
      muscle biopsies. Furthermore, we investigated the protein abundance of the myosin
      heavy chain isoforms and the components of the mitochondrial electron transport
      chain in skeletal muscle from people with NGT or T2D. mRNA of selected sarcomeric
      z-disk proteins was also assessed. Although the prevalence of the ACTN3 577XX
      genotype was higher in T2D patients, genotype distribution was unrelated to
      metabolic control or obesity. ACTN2 and ACTN3 mRNA expression and protein
      abundance was unchanged between NGT and T2D participants. Protein abundance of
      mitochondrial complexes II and IV was related to genotype and glucose tolerance
      status. Gene expression of sarcomeric z-disk proteins was increased in skeletal
      muscle from NGT participants with the ACTN3 577XX genotype. While genetic
      variation in ACTN3 does not influence metabolic control, genotype does appear to
      influence gene expression of other sarcomeric proteins, which could contribute to
      the functional properties of skeletal muscle and the fatigue-resistant phenotype
      associated with the R577X polymorphism. 

PMID- 25780093
TI  - Strengthening of the intestinal epithelial tight junction by Bifidobacterium
      bifidum.
AB  - Epithelial barrier dysfunction has been implicated as one of the major
      contributors to the pathogenesis of inflammatory bowel disease. The increase in
      intestinal permeability allows the translocation of luminal antigens across the
      intestinal epithelium, leading to the exacerbation of colitis. Thus, therapies
      targeted at specifically restoring tight junction barrier function are thought to
      have great potential as an alternative or supplement to immunology-based
      therapies. In this study, we screened Bifidobacterium, Enterococcus, and
      Lactobacillus species for beneficial microbes to strengthen the intestinal
      epithelial barrier, using the human intestinal epithelial cell line (Caco-2) in
      an in vitro assay. Some Bifidobacterium and Lactobacillus species prevented
      epithelial barrier disruption induced by TNF-alpha, as assessed by measuring the
      transepithelial electrical resistance (TER). Furthermore, live Bifidobacterium
      species promoted wound repair in Caco-2 cell monolayers treated with TNF-alpha
      for 48 h. Time course (1)H-NMR-based metabonomics of the culture supernatant
      revealed markedly enhanced production of acetate after 12 hours of coincubation
      of B. bifidum and Caco-2. An increase in TER was observed by the administration
      of acetate to TNF-alpha-treated Caco-2 monolayers. Interestingly, acetate-induced
      TER-enhancing effect in the coculture of B. bifidum and Caco-2 cells depends on
      the differentiation stage of the intestinal epithelial cells. These results
      suggest that Bifidobacterium species enhance intestinal epithelial barrier
      function via metabolites such as acetate. 

PMID- 25780094
TI  - Universal and individual characteristics of postural sway during quiet standing
      in healthy young adults.
AB  - The time course of the center of pressure (CoP) during human quiet standing,
      corresponding to body sway, is a stochastic process, influenced by a variety of
      features of the underlying neuro-musculo-skeletal system, such as postural
      stability and flexibility. Due to complexity of the process, sway patterns have
      been characterized in an empirical way by a number of indices, such as sway size
      and mean sway velocity. Here, we describe a statistical approach with the aim of
      estimating "universal" indices, namely parameters that are independent of
      individual body characteristics and thus are not "hidden" by the presence of
      individual, daily, and circadian variations of sway; in this manner it is
      possible to characterize the common aspects of sway dynamics across healthy young
      adults, in the assumption that they might reflect underlying neural control
      during quiet standing. Such universal indices are identified by analyzing intra
      and inter-subject variability of various indices, after sorting out individual
      specific indices that contribute to individual discriminations. It is shown that
      the universal indices characterize mainly slow components of sway, such as
      scaling exponents of power-law behavior at a low-frequency regime. On the other
      hand, most of the individual-specific indices contributing to the individual
      discriminations exhibit significant correlation with body parameters, and they
      can be associated with fast oscillatory components of sway. These results are
      consistent with a mechanistic hypothesis claiming that the slow and the fast
      components of sway are associated, respectively, with neural control and
      biomechanics, supporting our assumption that the universal characteristics of
      postural sway might represent neural control strategies during quiet standing. 

PMID- 25780095
TI  - Vitamin D deficiency aggravates ischemic acute kidney injury in rats.
AB  - Vitamin D deficiency (VDD) increases the risk of death in hospitalized patients.
      Renal ischemia/reperfusion injury (IRI) induces acute kidney injury (AKI), which
      activates cell cycle inhibitors, including p21, a cyclin-dependent kinase
      inhibitor and genomic target of 25-hydroxyvitamin D, which is in turn a potent
      immunomodulator with antiproliferative effects. In this study, we assess the
      impact of VDD in renal IRI. Wistar rats were divided into groups, each evaluated
      for 30 days: control (receiving a standard diet); VDD (receiving a vitamin D-free
      diet); IRI (receiving a standard diet and subjected to 45-min bilateral renal
      ischemia on day 28); and VDD + IRI (receiving a vitamin D-free diet and subjected
      to 45-min bilateral renal ischemia on day 28). At 48 h after IRI, animals were
      euthanized; blood, urine, and kidney tissue samples were collected. Compared with
      IRI rats, VDD + IRI rats showed a more severe decrease in glomerular filtration
      rate, greater urinary protein excretion, a higher kidney/body weight ratio and
      lower renal aquaporin 2 expression, as well as greater morphological damage,
      characterized by increased interstitial area and tubular necrosis. Our results
      suggest that the severity of tubular damage in IRI may be associated with
      downregulation of vitamin D receptors and p21. VDD increases renal inflammation,
      cell proliferation and cell injury in ischemic AKI. 

PMID- 25780096
TI  - The caspase inhibitor zVAD increases lung inflammation in pneumovirus infection
      in mice.
AB  - Severe respiratory syncytial virus (RSV) disease is a frequent cause of acute
      respiratory distress syndrome (ARDS) in young children, and is associated with
      marked lung epithelial injury and neutrophilic inflammation. Experimental studies
      on ARDS have shown that inhibition of apoptosis in the lungs reduces lung
      epithelial injury. However, the blockade of apoptosis in the lungs may also have
      deleterious effects by hampering viral clearance, and importantly, by enhancing
      or prolonging local proinflammatory responses. The aim of this study was to
      determine the effect of the broad caspase inhibitor Z-VAD(OMe)-FMK (zVAD) on
      inflammation and lung injury in a mouse pneumovirus model for severe RSV disease.
      Eight- to 11-week-old female C57BL/6OlaHsd mice were inoculated with the rodent
      specific pneumovirus pneumonia virus of mice (PVM) strain J3666 and received
      multiple injections of zVAD or vehicle (control) during the course of disease,
      after which they were studied for markers of apoptosis, inflammation, and lung
      injury on day 7 after infection. PVM-infected mice that received zVAD had a
      strong increase in neutrophil numbers in the lungs, which was associated with
      decreased neutrophil apoptosis. Furthermore, zVAD treatment led to higher
      concentrations of several proinflammatory cytokines in the lungs and more weight
      loss in PVM-infected mice. In contrast, zVAD did not reduce apoptosis of lung
      epithelial cells and did not affect the degree of lung injury, permeability, and
      viral titers in PVM disease. We conclude that zVAD has an adverse effect in
      severe pneumovirus disease in mice by enhancing the lung proinflammatory
      response. 

PMID- 25780098
TI  - Twenty years of RNA: then and now.

PMID- 25780099
TI  - RNA World research-still evolving.

PMID- 25780100
TI  - RNA-RNA base-pairing: theme and variations.

PMID- 25780097
TI  - A high-resolution tissue-specific proteome and phosphoproteome atlas of maize
      primary roots reveals functional gradients along the root axes.
AB  - A high-resolution proteome and phosphoproteome atlas of four maize (Zea mays)
      primary root tissues, the cortex, stele, meristematic zone, and elongation zone,
      was generated. High-performance liquid chromatography coupled with tandem mass
      spectrometry identified 11,552 distinct nonmodified and 2,852 phosphorylated
      proteins across the four root tissues. Two gradients reflecting the abundance of
      functional protein classes along the longitudinal root axis were observed. While
      the classes RNA, DNA, and protein peaked in the meristematic zone, cell wall,
      lipid metabolism, stress, transport, and secondary metabolism culminated in the
      differentiation zone. Functional specialization of tissues is underscored by six
      of 10 cortex-specific proteins involved in flavonoid biosynthesis. Comparison of
      this data set with high-resolution seed and leaf proteome studies revealed 13%
      (1,504/11,552) root-specific proteins. While only 23% of the 1,504 root-specific
      proteins accumulated in all four root tissues, 61% of all 11,552 identified
      proteins accumulated in all four root tissues. This suggests a much higher degree
      of tissue-specific functionalization of root-specific proteins. In summary, these
      data illustrate the remarkable plasticity of the proteomic landscape of maize
      primary roots and thus provide a starting point for gaining a better
      understanding of their tissue-specific functions.

PMID- 25780101
TI  - Brave new RNA world.

PMID- 25780102
TI  - The RNA Society: after 20 years clearly a big success.

PMID- 25780103
TI  - Present at the creation.

PMID- 25780104
TI  - Lessons from the RNA World: humility and hubris.

PMID- 25780105
TI  - tRNA processing, modification, and subcellular dynamics: past, present, and
      future.

PMID- 25780106
TI  - Twenty years of RNA crystallography.

PMID- 25780107
TI  - The amazing web of post-transcriptional gene control: the sum of small changes
      can make for significant consequences.

PMID- 25780108
TI  - Twenty years: a very short sequence in the RNA world.

PMID- 25780109
TI  - RNA surveillance and the exosome.

PMID- 25780110
TI  - Coffee with Ribohipster.

PMID- 25780111
TI  - Reflections on the RNA journal at 20 and its role in the question of splice site
      choice.

PMID- 25780112
TI  - Splicing: still so much to learn.

PMID- 25780113
TI  - RNA folding retrospective: lessons from ribozymes big and small.

PMID- 25780114
TI  - On the shoulders of giants.

PMID- 25780115
TI  - Musings on 20 years of RNA.

PMID- 25780116
TI  - Reminiscences on my life with RNA: a self-indulgent perspective.

PMID- 25780117
TI  - Accelerating expansion.

PMID- 25780118
TI  - RNA reflections: converging on Hfq.

PMID- 25780119
TI  - Twenty years.

PMID- 25780120
TI  - The wonder of RNA: a personal reflection of the last 20 years.

PMID- 25780121
TI  - The evolution of RNase P.

PMID- 25780122
TI  - The long unfinished march towards understanding microRNA-mediated repression.

PMID- 25780123
TI  - Know thyself.

PMID- 25780124
TI  - Learning from ribozymes.

PMID- 25780125
TI  - Methods to our madness.

PMID- 25780126
TI  - Reflections on the RNA world.

PMID- 25780127
TI  - RNA catalysis--is that it?

PMID- 25780128
TI  - A journey to the end of the message.

PMID- 25780129
TI  - RNA: yesterday, today and tomorrow.

PMID- 25780130
TI  - Finding the unexpected--how we identified a second class of introns and the U12
      dependent spliceosome.

PMID- 25780131
TI  - We'll always have RNA.

PMID- 25780132
TI  - RNPs and autoimmunity: 20 years later.

PMID- 25780133
TI  - Reflections on the 20th anniversary of RNA.

PMID- 25780134
TI  - The importance of being modified: an unrealized code to RNA structure and
      function.

PMID- 25780135
TI  - RNAi, the guiding principle and keeping family happy.

PMID- 25780136
TI  - Fifty to 100 times the size!

PMID- 25780137
TI  - Central dogma alchemy.

PMID- 25780138
TI  - Riboswitches: still a lot of undiscovered country.

PMID- 25780139
TI  - The beginning of RNA.

PMID- 25780140
TI  - Way to go, RNA.

PMID- 25780141
TI  - A decades-long journey with mobile introns.

PMID- 25780142
TI  - The union of transcription and mRNA processing: 20 years of coupling.

PMID- 25780143
TI  - Pre-mRNA splicing: from protein-coding to noncoding RNAs.

PMID- 25780144
TI  - Reflections for the 20th anniversary issue of RNA journal.

PMID- 25780145
TI  - An RNA mystery and its denouement.

PMID- 25780146
TI  - My RNA world: past, present and future.

PMID- 25780147
TI  - RNA imaging: seeing is believing.

PMID- 25780148
TI  - Finding the rules of splicing, and using them ... alternatively.

PMID- 25780149
TI  - Two degrading decades for RNA.

PMID- 25780150
TI  - RNA splicing for 30 years.

PMID- 25780151
TI  - Caps and tales.

PMID- 25780152
TI  - A long and winding road to the RNA world.

PMID- 25780153
TI  - The virology-RNA biology connection.

PMID- 25780154
TI  - Metals and RNA: scenes from a road trip.

PMID- 25780155
TI  - Twenty years of bacterial RNases and RNA processing: how we've matured.

PMID- 25780156
TI  - Reflections on 20 years of RNA.

PMID- 25780157
TI  - On the occasion of the 20th anniversary of the RNA journal.

PMID- 25780158
TI  - Homology searches for structural RNAs: from proof of principle to practical use.

PMID- 25780159
TI  - RNA as a conception.

PMID- 25780160
TI  - Reflections on 20 years of RNA science.

PMID- 25780161
TI  - Back to the future of RNA structure.

PMID- 25780162
TI  - Assembly of RNPs: help needed.

PMID- 25780163
TI  - Discovery and investigation of the GAIT translational control system.

PMID- 25780164
TI  - Yes, SiR.

PMID- 25780165
TI  - The continuing allure of RNA.

PMID- 25780166
TI  - RNA modification: the Golden Period 1995-2015.

PMID- 25780167
TI  - rRNA--the evolution of that magic molecule.

PMID- 25780168
TI  - Mighty tiny.

PMID- 25780169
TI  - RNA and lessons from viruses.

PMID- 25780170
TI  - A big score for RNA.

PMID- 25780171
TI  - Translational control 1995-2015: unveiling molecular underpinnings and roles in
      human biology.

PMID- 25780172
TI  - The best of 25 years: mRNA 3'end processing.

PMID- 25780173
TI  - Post-transcriptional modifications to tRNA--a response to the genetic code
      degeneracy.

PMID- 25780174
TI  - The early days of RNomics.

PMID- 25780175
TI  - Transfer RNA comes of age.

PMID- 25780176
TI  - An origin story: ribozyme catalysis by the ribosome.

PMID- 25780177
TI  - The awesome power of ribosome profiling.

PMID- 25780178
TI  - From exotic to exciting.

PMID- 25780179
TI  - What will the future hold: RNP quality control and degradation.

PMID- 25780180
TI  - The new era of RNA modification.

PMID- 25780181
TI  - Experiences gathered and lessons learned from 20 years of RNA structure.

PMID- 25780182
TI  - Twenty years of RNA and mRNA decay.

PMID- 25780183
TI  - A short biased history of RNA viruses.

PMID- 25780184
TI  - Transcriptional control of alternative splicing along time: ideas change,
      experiments remain.

PMID- 25780185
TI  - Polyadenylation in E. coli: a 20 year odyssey.

PMID- 25780186
TI  - Two decades of miRNA biology: lessons and challenges.

PMID- 25780187
TI  - Sleeping Beauty and the Beast (of pervasive transcription).

PMID- 25780188
TI  - A magnesium-binding nucleotide, a remodeling ATPase, and a wonderful RNA world.

PMID- 25780189
TI  - A journey.

PMID- 25780190
TI  - Thoughts on NGS, alternative splicing and what we still need to know.

PMID- 25780191
TI  - A career in (mRNA) decay.

PMID- 25780192
TI  - Twenty years of RNA: reflections on post-transcriptional regulation.

PMID- 25780193
TI  - Twenty years of RNA: reflections from the RNP world.

PMID- 25780194
TI  - Ribosomal RNA, the lens into life.

PMID- 25780195
TI  - Gene expression regulation: lessons from noncoding RNAs.

PMID- 25780196
TI  - Twenty years of technology.

PMID- 25780197
TI  - In the beginning was the U1A protein: a personal reflection.

PMID- 25780198
TI  - RNA: master or servant?

PMID- 25780199
TI  - RNA modification and the epitranscriptome; the next frontier.

PMID- 25780200
TI  - Looking for the key to secrets of RNA under the lamp-post.

PMID- 25780201
TI  - My adventure in tRNA biology, so far.

PMID- 25780202
TI  - MicroRNAs: heralds of the noncoding RNA revolution.

PMID- 25780203
TI  - Fair and prompt.

PMID- 25780204
TI  - RNA dances to center stage.

PMID- 25780205
TI  - Rediscovering RNA.

PMID- 25780206
TI  - RNA and the synapse.

PMID- 25780207
TI  - Twenty years of RNA.

PMID- 25780208
TI  - Twenty-five plus years of an RNA addiction.

PMID- 25780209
TI  - Reflections on 20 years of RNA folding, dynamics, and structure.

PMID- 25780210
TI  - Personal reflection (RNA journal 20th anniversary).

PMID- 25780211
TI  - Dynamic RNA world.

PMID- 25780212
TI  - Soups & SELEX for the origin of life.

PMID- 25780213
TI  - Two decades of RNA as I see it.

PMID- 25780214
TI  - RNA capping: progress and prospects.

PMID- 25780215
TI  - Study of mRNA turnover never decays.

PMID- 25780216
TI  - The most unlikely places.

PMID- 25780217
TI  - A tRNA-guided research journey from synthetic chemistry to synthetic biology.

PMID- 25780218
TI  - Personal reflections on RNA: an emphasis on trypanosomes.

PMID- 25780219
TI  - My encounter with RNA.

PMID- 25780220
TI  - RNA rules!

PMID- 25780221
TI  - Twenty years of RNA: the discovery of microRNAs.

PMID- 25780222
TI  - An RNA biochemist's affair with proteins.

PMID- 25780223
TI  - Going viral: riding the RNA wave to discovery.

PMID- 25780224
TI  - Twenty years of ribosome assembly and ribosomopathies.

PMID- 25780225
TI  - RNA clubs.

PMID- 25780226
TI  - An RNAmazing 20 years.

PMID- 25780227
TI  - Are we there yet?

PMID- 25780228
TI  - Assembly of ribosomes in eukaryotes.

PMID- 25780229
TI  - Ahead and behind: a small, small RNA world.

PMID- 25780230
TI  - Ribosome biochemistry in crystal structure determination.

PMID- 25780231
TI  - Physical behaviour of anthropogenic light propagation into the nocturnal
      environment.
AB  - Propagation of artificial light at night (ALAN) in the environment is now known
      to have non negligible consequences on fauna, flora and human health. These
      consequences depend on light levels and their spectral power distributions, which
      in turn rely on the efficiency of various physical processes involved in the
      radiative transfer of this light into the atmosphere and its interactions with
      the built and natural environment. ALAN can affect the living organisms by direct
      lighting and indirect lighting (scattered by the sky and clouds and/or reflected
      by local surfaces). This paper mainly focuses on the behaviour of the indirect
      light scattered under clear sky conditions. Various interaction processes between
      anthropogenic light sources and the natural environment are discussed. This work
      mostly relies on a sensitivity analysis conducted with the light pollution
      radiative transfer model, Illumina (Aube et al. 2005 Light pollution modelling
      and detection in a heterogeneous environment: toward a night-time aerosol optical
      depth retrieval method. In Proc. SPIE 2005, vol. 5890, San Diego, California,
      USA). More specifically, the impact of (i) the molecular and aerosol scattering
      and absorption, (ii) the second order of scattering, (iii) the topography and
      obstacle blocking, (iv) the ground reflectance and (v) the spectrum of light
      devices and their angular emission functions are examined. This analysis
      considers different behaviour as a function of the distance from the city centre,
      along with different zenith viewing angles in the principal plane. 

PMID- 25780232
TI  - Does light pollution alter daylength? A test using light loggers on free-ranging
      European blackbirds (Turdus merula).
AB  - Artificial light at night is one of the most apparent environmental changes
      accompanying anthropogenic habitat change. The global increase in light pollution
      poses new challenges to wild species, but we still have limited understanding of
      the temporal and spatial pattern of exposure to light at night. In particular, it
      has been suggested by several studies that animals exposed to light pollution,
      such as songbirds, perceive a longer daylength compared with conspecifics living
      in natural darker areas, but direct tests of such a hypothesis are still lacking.
      Here, we use a combination of light loggers deployed on individual European
      blackbirds, as well as automated radio-telemetry, to examine whether urban birds
      are exposed to a longer daylength than forest counterparts. We first used
      activity data from forest birds to determine the level of light intensity which
      defines the onset and offset of daily activity in rural areas. We then used this
      value as threshold to calculate the subjective perceived daylength of both forest
      and urban blackbirds. In March, when reproductive growth occurs, urban birds were
      exposed on average to a 49-min longer subjective perceived daylength than forest
      ones, which corresponds to a 19-day difference in photoperiod at this time of the
      year. In the field, urban blackbirds reached reproductive maturity 19 day earlier
      than rural birds, suggesting that light pollution could be responsible of most of
      the variation in reproductive timing found between urban and rural dwellers. We
      conclude that light at night is the most relevant change in ambient light
      affecting biological rhythms in avian urban-dwellers, most likely via a
      modification of the perceived photoperiod. 

PMID- 25780233
TI  - Electric light, particularly at night, disrupts human circadian rhythmicity: is
      that a problem?
AB  - Over the past 3 billion years, an endogenous circadian rhythmicity has developed
      in almost all life forms in which daily oscillations in physiology occur. This
      allows for anticipation of sunrise and sunset. This physiological rhythmicity is
      kept at precisely 24 h by the daily cycle of sunlight and dark. However, since
      the introduction of electric lighting, there has been inadequate light during the
      day inside buildings for a robust resetting of the human endogenous circadian
      rhythmicity, and too much light at night for a true dark to be detected; this
      results in circadian disruption and alters sleep/wake cycle, core body
      temperature, hormone regulation and release, and patterns of gene expression
      throughout the body. The question is the extent to which circadian disruption
      compromises human health, and can account for a portion of the modern pandemics
      of breast and prostate cancers, obesity, diabetes and depression. As societies
      modernize (i.e. electrify) these conditions increase in prevalence. There are a
      number of promising leads on putative mechanisms, and epidemiological findings
      supporting an aetiologic role for electric lighting in disease causation. These
      include melatonin suppression, circadian gene expression, and connection of
      circadian rhythmicity to metabolism in part affected by haem iron intake and
      distribution.

PMID- 25780234
TI  - Artificial light at night: melatonin as a mediator between the environment and
      epigenome.
AB  - The adverse effects of excessive use of artificial light at night (ALAN) are
      becoming increasingly evident and associated with several health problems
      including cancer. Results of epidemiological studies revealed that the increase
      in breast cancer incidents co-distribute with ALAN worldwide. There is compiling
      evidence that suggests that melatonin suppression is linked to ALAN-induced
      cancer risks, but the specific genetic mechanism linking environmental exposure
      and the development of disease is not well known. Here we propose a possible
      genetic link between environmental exposure and tumorigenesis processes. We
      discuss evidence related to the relationship between epigenetic remodelling and
      oncogene expression. In breast cancer, enhanced global hypomethylation is
      expected in oncogenes, whereas in tumour suppressor genes local hypermethylation
      is recognized in the promoter CpG chains. A putative mechanism of action
      involving epigenetic modifications mediated by pineal melatonin is discussed in
      relation to cancer prevalence. Taking into account that ALAN-induced epigenetic
      modifications are reversible, early detection of cancer development is of great
      significance in the treatment of the disease. Therefore, new biomarkers for
      circadian disruption need to be developed to prevent ALAN damage.

PMID- 25780235
TI  - Melatonin: a possible link between the presence of artificial light at night and
      reductions in biological fitness.
AB  - The mechanisms underpinning the ecological impacts of the presence of artificial
      night lighting remain elusive. One suspected underlying cause is that the
      presence of light at night (LAN) supresses nocturnal production of melatonin, a
      key driver of biological rhythm and a potent antioxidant with a proposed role in
      immune function. Here, we briefly review the evidence for melatonin as the link
      between LAN and changes in behaviour and physiology. We then present preliminary
      data supporting the potential for melatonin to act as a recovery agent mitigating
      the negative effects of LAN in an invertebrate. Adult crickets (Teleogryllus
      commodus), exposed to constant illumination, were provided with dietary melatonin
      (concentrations: 0, 10 or 100 ug ml(-1)) in their drinking water. We then
      compared survival, lifetime fecundity and, over a 4-week period, immune function
      (haemocyte concentration, lysozyme-like and phenoloxidase (PO) activity).
      Melatonin supplementation was able only partially to mitigate the detrimental
      effects of LAN: it did not improve survival or fecundity or PO activity, but it
      had a largely dose-dependent positive effect on haemocyte concentration and
      lysozyme-like activity. We discuss the implications of these relationships, as
      well as the usefulness of invertebrates as model species for future studies that
      explore the effects of LAN.

PMID- 25780236
TI  - Barriers and benefits: implications of artificial night-lighting for the
      distribution of common bats in Britain and Ireland.
AB  - Artificial lighting is a particular problem for animals active at night.
      Approximately 69% of mammal species are nocturnal, and one-third of these are
      bats. Due to their extensive movements-both on a nightly basis to exploit
      ephemeral food supplies, and during migration between roosts-bats have an
      unusually high probability of encountering artificial light in the landscape.
      This paper reviews the impacts of lighting on bats and their prey, exploring the
      direct and indirect consequences of lighting intensity and spectral composition.
      In addition, new data from large-scale surveys involving more than 265 000 bat
      calls at more than 600 locations in two countries are presented, showing that
      prevalent street-lighting types are not generally linked with increased activity
      of common and widespread bat species. Such bats, which are important to ecosystem
      function, are generally considered 'light-attracted' and likely to benefit from
      the insect congregations that form at lights. Leisler's bat (Nyctalus leisleri)
      may be an exception, being more frequent in lit than dark transects. For common
      pipistrelle bats (Pipistrellus pipistrellus), lighting is negatively associated
      with their distribution on a landscape scale, but there may be local increases in
      habitats with good tree cover. Research is now needed on the impacts of sky glow
      and glare for bat navigation, and to explore the implications of lighting for
      habitat matrix permeability.

PMID- 25780237
TI  - Tuning the white light spectrum of light emitting diode lamps to reduce
      attraction of nocturnal arthropods.
AB  - Artificial lighting allows humans to be active at night, but has many unintended
      consequences, including interference with ecological processes, disruption of
      circadian rhythms and increased exposure to insect vectors of diseases. Although
      ultraviolet and blue light are usually most attractive to arthropods, degree of
      attraction varies among orders. With a focus on future indoor lighting
      applications, we manipulated the spectrum of white lamps to investigate the
      influence of spectral composition on number of arthropods attracted. We compared
      numbers of arthropods captured at three customizable light-emitting diode (LED)
      lamps (3510, 2704 and 2728 K), two commercial LED lamps (2700 K), two commercial
      compact fluorescent lamps (CFLs; 2700 K) and a control. We configured the three
      custom LEDs to minimize invertebrate attraction based on published attraction
      curves for honeybees and moths. Lamps were placed with pan traps at an urban and
      two rural study sites in Los Angeles, California. For all invertebrate orders
      combined, our custom LED configurations were less attractive than the commercial
      LED lamps or CFLs of similar colour temperatures. Thus, adjusting spectral
      composition of white light to minimize attracting nocturnal arthropods is
      feasible; not all lights with the same colour temperature are equally attractive
      to arthropods.

PMID- 25780238
TI  - Light pollution alters the phenology of dawn and dusk singing in common European
      songbirds.
AB  - Artificial night lighting is expanding globally, but its ecological consequences
      remain little understood. Animals often use changes in day length as a cue to
      time seasonal behaviour. Artificial night lighting may influence the perception
      of day length, and may thus affect both circadian and circannual rhythms. Over a
      3.5 month period, from winter to breeding, we recorded daily singing activity of
      six common songbird species in 12 woodland sites, half of which were affected by
      street lighting. We previously reported on analyses suggesting that artificial
      night lighting affects the daily timing of singing in five species. The main aim
      of this study was to investigate whether the presence of artificial night
      lighting is also associated with the seasonal occurrence of dawn and dusk
      singing. We found that in four species dawn and dusk singing developed earlier in
      the year at sites exposed to light pollution. We also examined the effects of
      weather conditions and found that rain and low temperatures negatively affected
      the occurrence of dawn and dusk singing. Our results support the hypothesis that
      artificial night lighting alters natural seasonal rhythms, independently of other
      effects of urbanization. The fitness consequences of the observed changes in
      seasonal timing of behaviour remain unknown.

PMID- 25780239
TI  - The impacts of new street light technologies: experimentally testing the effects
      on bats of changing from low-pressure sodium to white metal halide.
AB  - Artificial light at night is a major feature of anthropogenic global change and
      is increasingly recognized as affecting biodiversity, often negatively. On a
      global scale, newer technology white lights are replacing orange sodium lights to
      reduce energy waste. In 2009, Cornwall County Council (UK) commenced replacement
      of existing low-pressure sodium (LPS) high intensity discharge (HID) street
      lights with new Phillips CosmoPolis white ceramic metal halide street lights to
      reduce energy wastage. This changeover provided a unique collaborative
      opportunity to implement a before-after-control-impact field experiment to
      investigate the ecological effects of newly installed broad spectrum light
      technologies. Activity of the bat species Pipistrellus pipistrellus, P. pygmaeus
      and Nyctalus/Eptesicus spp. was significantly higher at metal halide than LPS
      lights, as found in other studies of bat activity at old technology (i.e. mercury
      vapour) white light types. No significant difference was found in feeding
      attempts per bat pass between light types, though more passes overall were
      recorded at metal halide lights. Species-specific attraction of bats to the metal
      halide lights could have cascading effects at lower trophic levels. We highlight
      the need for further research on possible ecosystem-level effects of light
      technologies before they are installed on a wide scale.

PMID- 25780240
TI  - Effects of nocturnal illumination on life-history decisions and fitness in two
      wild songbird species.
AB  - The effects of artificial night lighting on animal behaviour and fitness are
      largely unknown. Most studies report short-term consequences in locations that
      are also exposed to other anthropogenic disturbance. We know little about how the
      effects of nocturnal illumination vary with different light colour compositions.
      This is increasingly relevant as the use of LED lights becomes more common, and
      LED light colour composition can be easily adjusted. We experimentally
      illuminated previously dark natural habitat with white, green and red light, and
      measured the effects on life-history decisions and fitness in two free-living
      songbird species, the great tit (Parus major) and pied flycatcher (Ficedula
      hypoleuca) in two consecutive years. In 2013, but not in 2014, we found an effect
      of light treatment on lay date, and of the interaction of treatment and distance
      to the nearest lamp post on chick mass in great tits but not in pied flycatchers.
      We did not find an effect in either species of light treatment on breeding
      densities, clutch size, probability of brood failure, number of fledglings and
      adult survival. The finding that light colour may have differential effects opens
      up the possibility to mitigate negative ecological effects of nocturnal
      illumination by using different light spectra.

PMID- 25780241
TI  - Experimental illumination of natural habitat--an experimental set-up to assess
      the direct and indirect ecological consequences of artificial light of different
      spectral composition.
AB  - Artificial night-time illumination of natural habitats has increased dramatically
      over the past few decades. Generally, studies that assess the impact of
      artificial light on various species in the wild make use of existing illumination
      and are therefore correlative. Moreover, studies mostly focus on short-term
      consequences at the individual level, rather than long-term consequences at the
      population and community level-thereby ignoring possible unknown cascading
      effects in ecosystems. The recent change to LED lighting has opened up the
      exciting possibility to use light with a custom spectral composition, thereby
      potentially reducing the negative impact of artificial light. We describe here a
      large-scale, ecosystem-wide study where we experimentally illuminate forest-edge
      habitat with different spectral composition, replicated eight times. Monitoring
      of species is being performed according to rigid protocols, in part using a
      citizen-science-based approach, and automated where possible. Simultaneously, we
      specifically look at alterations in behaviour, such as changes in activity, and
      daily and seasonal timing. In our set-up, we have so far observed that
      experimental lights facilitate foraging activity of pipistrelle bats, suppress
      activity of wood mice and have effects on birds at the community level, which
      vary with spectral composition. Thus far, we have not observed effects on moth
      populations, but these and many other effects may surface only after a longer
      period of time.

PMID- 25780242
TI  - Microbial diversity and community respiration in freshwater sediments influenced
      by artificial light at night.
AB  - An increasing proportion of the Earth's surface is illuminated at night. In
      aquatic ecosystems, artificial light at night (ALAN) may influence microbial
      communities living in the sediments. These communities are highly diverse and
      play an important role in the global carbon cycle. We combined field and
      laboratory experiments using sediments from an agricultural drainage system to
      examine how ALAN affects communities and alters carbon mineralization. Two
      identical light infrastructures were installed parallel to a drainage ditch
      before the start of the experiment. DNA metabarcoding indicated that both
      sediment communities were similar. After one was lit for five months (July
      December 2012) we observed an increase in photoautotroph abundance (diatoms,
      Cyanobacteria) in ALAN-exposed sediments. In laboratory incubations mimicking
      summer and winter (six weeks each), communities in sediments that were exposed to
      ALAN for 1 year (July 2012-June 2013) showed less overall seasonal change
      compared with ALAN-naive sediments. Nocturnal community respiration was reduced
      in ALAN-exposed sediments. In long-term exposed summer-sediments, we observed a
      shift from negative to positive net ecosystem production. Our results indicate
      ALAN may alter sediment microbial communities over time, with implications for
      ecosystem-level functions. It may thus have the potential to transform inland
      waters to nocturnal carbon sinks.

PMID- 25780243
TI  - Cascading effects of artificial light at night: resource-mediated control of
      herbivores in a grassland ecosystem.
AB  - Artificial light at night has a wide range of biological effects on both plants
      and animals. Here, we review mechanisms by which artificial light at night may
      restructure ecological communities by modifying the interactions between species.
      Such mechanisms may be top-down (predator, parasite or grazer controlled), bottom
      up (resource-controlled) or involve non-trophic processes, such as pollination,
      seed dispersal or competition. We present results from an experiment
      investigating both top-down and bottom-up effects of artificial light at night on
      the population density of pea aphids Acyrthosiphon pisum in a diverse artificial
      grassland community in the presence and absence of predators and under low-level
      light of different spectral composition. We found no evidence for top-down
      control of A. pisum in this system, but did find evidence for bottom-up effects
      mediated through the impact of light on flower head density in a leguminous food
      plant. These results suggest that physiological effects of light on a plant
      species within a diverse plant community can have detectable demographic effects
      on a specialist herbivore.

PMID- 25780245
TI  - Correction to 'The mystery of extreme non-coding conservation'.

PMID- 25780244
TI  - The biological impacts of artificial light at night: the research challenge.

PMID- 25780246
TI  - Additive manufacturing. Continuous liquid interface production of 3D objects.
AB  - Additive manufacturing processes such as 3D printing use time-consuming, stepwise
      layer-by-layer approaches to object fabrication. We demonstrate the continuous
      generation of monolithic polymeric parts up to tens of centimeters in size with
      feature resolution below 100 micrometers. Continuous liquid interface production
      is achieved with an oxygen-permeable window below the ultraviolet image
      projection plane, which creates a "dead zone" (persistent liquid interface) where
      photopolymerization is inhibited between the window and the polymerizing part. We
      delineate critical control parameters and show that complex solid parts can be
      drawn out of the resin at rates of hundreds of millimeters per hour. These print
      speeds allow parts to be produced in minutes instead of hours. 

PMID- 25780247
TI  - Requirement for specific gravity and creatinine adjustments for urinary steroids
      and luteinizing hormone concentrations in adolescents.
AB  - OBJECTIVES: Urinary hormone concentrations are often adjusted to correct for
      hydration status. We aimed to determine whether first morning void urine hormones
      in growing adolescents require adjustments and, if so, whether urinary creatinine
      or specific gravity are better adjustments. DESIGN AND METHODS: The study
      population was adolescents aged 10.1 to 14.3 years initially who provided fasting
      morning blood samples at 0 and 12 months (n = 343) and first morning urine every
      three months (n = 644). Unadjusted, creatinine and specific gravity-adjusted
      hormonal concentrations were compared by Deming regression and Bland-Altman
      analysis and grouped according to self-rated Tanner stage or chronological age. F
      ratios for self-rated Tanner stages and age groups were used to compare
      unadjusted and adjusted hormonal changes in growing young adolescents.
      Correlations of paired serum and urinary hormonal concentration of unadjusted and
      creatinine and specific gravity-adjusted were also compared. RESULTS: Fasting
      first morning void hormone concentrations correlated well and were unbiased
      between unadjusted or adjusted by either creatinine or specific gravity. Urine
      creatinine concentration increases with Tanner stages, age and male gender
      whereas urine specific gravity was not influenced by Tanner stage, age or gender.
      Adjustment by creatinine or specific gravity of urinary luteinizing hormone,
      estradiol, testosterone, dihydrotestosterone and dehydroepiandrosterone
      concentrations did not improve correlation with paired serum concentrations.
      CONCLUSIONS: Urine steroid and luteinizing hormone concentrations in first
      morning void samples of adolescents are not significantly influenced by hydration
      status and may not require adjustments; however, if desired, both creatinine and
      specific gravity adjustments are equally suitable.

PMID- 25780248
TI  - The effect of storage conditions on sample stability in the routine clinical
      laboratory.
AB  - BACKGROUND: 'Add-on' tests are often requested for samples already in the
      laboratory. This study was carried out to assess the stability of common analytes
      in uncapped samples stored in different conditions, and therefore their
      suitability for 'add-on' requests. METHODS: Storage conditions evaluated included
      initial storage at room temperature for 16 hours, followed by storage at 4C
      (Group 1: current conditions employed in the laboratory), compared with storage
      at 4C immediately following analysis (Group 2: optimum storage conditions).
      RESULTS: Some analytes were not suitable for 'add-ons' when samples were stored
      in either storage condition, whereas some were suitable for 'add-ons'
      irrespective of storage condition. Storage conditions influenced the suitability
      of 'add-on' tests for a proportion of analytes including urea, amylase, total
      protein, alkaline phosphatase, adjusted calcium, lactate dehydrogenase,
      triglycerides, HDL cholesterol and total cholesterol; these analytes were stable
      in optimum conditions (Group 2) but not in current conditions (Group 1).
      CONCLUSIONS: 'Add-on' tests can only be safely performed on a proportion of
      routine analytes. For some analytes, storage conditions affect their suitability
      for delayed analysis.

PMID- 25780249
TI  - Infliximab and adalimumab are stable in whole blood clotted samples for seven
      days at room temperature.
AB  - INTRODUCTION: The biologic anti-tumour necrosis factor alpha (anti-TNFalpha)
      agents infliximab and adalimumab are monoclonal antibodies with binding
      specificity to TNFalpha, which are used for the treatment of Crohn's disease.
      Clinical response is varied from complete with mucosal healing, to primary non
      response, loss of response and adverse drug reactions. Measuring trough blood
      levels of infliximab and adalimumab may guide clinical management. The sample
      handling requirements for infliximab and adalimumab were previously unknown. AIM:
      The aim of this study was to determine the in vitro stability of infliximab and
      adalimumab in samples stored for up to seven days at room temperature. METHODS:
      Samples were stored as clotted whole blood or serum at room temperature for up to
      seven days, before being frozen (-20C) and analysed as a batch for either
      infliximab or adalimumab. RESULTS: No significant difference between the
      concentration of infliximab and adalimumab measured in samples stored as serum or
      whole blood for seven days at room temperature, as compared to baseline was found
      (t-test; infliximab: P = .35 [serum], P = .38 [whole blood]; adalimumab: P = .12
      [serum], P = .49 [whole blood]). CONCLUSION: The stability of infliximab and
      adalimumab at room temperature for seven days allows samples to be posted direct
      from clinics and research centres to the analysing laboratory.

PMID- 25780250
TI  - Development of clinical pharmacy key performance indicators for hospital
      pharmacists using a modified Delphi approach.
AB  - BACKGROUND: Key performance indicators (KPIs) are quantifiable measures of
      quality. There are no published, systematically derived clinical pharmacy KPIs
      (cpKPIs). OBJECTIVE: A group of hospital pharmacists aimed to develop national
      cpKPIs to advance clinical pharmacy practice and improve patient care. METHODS: A
      cpKPI working group established a cpKPI definition, 8 evidence-derived cpKPI
      critical activity areas, 26 candidate cpKPIs, and 11 cpKPI ideal attributes in
      addition to 1 overall consensus criterion. Twenty-six clinical pharmacists and
      hospital pharmacy leaders participated in an internet-based 3-round modified
      Delphi survey. Panelists rated 26 candidate cpKPIs using 11 cpKPI ideal
      attributes and 1 overall consensus criterion on a 9-point Likert scale. A meeting
      was facilitated between rounds 2 and 3 to debate the merits and wording of
      candidate cpKPIs. Consensus was reached if 75% or more of panelists assigned a
      score of 7 to 9 on the consensus criterion during the third Delphi round.
      RESULTS: All panelists completed the 3 Delphi rounds, and 25/26 (96%) attended
      the meeting. Eight candidate cpKPIs met the consensus definition: (1) performing
      admission medication reconciliation (including best-possible medication history),
      (2) participating in interprofessional patient care rounds, (3) completing
      pharmaceutical care plans, (4) resolving drug therapy problems, (5) providing in
      person disease and medication education to patients, (6) providing discharge
      patient medication education, (7) performing discharge medication reconciliation,
      and (8) providing bundled, proactive direct patient care activities. CONCLUSIONS:
      A Delphi panel of hospital pharmacists was successful in determining 8 consensus
      cpKPIs. Measurement and assessment of these cpKPIs will serve to advance clinical
      pharmacy practice and improve patient care.

PMID- 25780251
TI  - Difficult airway and intubation in thyroid surgery.

PMID- 25780252
TI  - Detailed hearing and vestibular profiles in the patients with COCH mutations.
AB  - OBJECTIVES: To evaluate the clinical features of Japanese DFNA9 families with
      mutations of the COCH gene. METHODS: Mutation screening was performed using
      targeted next-generation sequencing (NGS) for 63 previously reported deafness
      genes. The progression of hearing loss and vestibular dysfunction were evaluated
      by pure-tone audiometry, caloric testing, cVEMP, and computed dynamic
      posturography. RESULTS: We detected 1 reported mutation of p.G88E and 2 novel
      mutations of p.I372T and p.C542R. The patients with the novel mutations of
      p.I372T and p.C542R within the vWFA2 domain showed early onset progressive
      hearing loss, and the patients with the p.G88E mutation showed late onset hearing
      loss and acute hearing deterioration over a short period. Vestibular symptoms
      were reported in the patients with p.G88E and p.C542R. Vestibular testing was
      performed for the family with the p.G88E mutation. Severe vestibular dysfunction
      was observed in the proband, and the proband's son showed unilateral semicircular
      canal dysfunction with mild hearing loss. CONCLUSIONS: Targeted exon resequencing
      of selected genes using NGS successfully identified mutations in the relatively
      rare deafness gene, COCH, in the Japanese population. The phenotype is compatible
      with that described in previous reports. Additional supporting evidence
      concerning progressive hearing loss and deterioration of vestibular function was
      obtained from our study.

PMID- 25780253
TI  - Germinal mosaicism in a family with BO syndrome.
AB  - OBJECTIVES: To clarify the existence of germinal mosaicism, we performed a
      genetic analysis of 2 siblings identified with an EYA1 mutation associated with
      branchiooto (BO) syndrome but who were born from normal parents. METHODS:
      Detailed data from the 2 affected siblings were collected for clinical diagnosis,
      with haplotype analysis also performed to prove germinal mosaicism. RESULTS: The
      2 sisters showed characteristic clinical features of BO syndrome (middle and
      inner ear anomalies, microtia, and auditory canal stenosis/atresia). Haplotype
      analysis confirmed the genetic relationship between the affected sisters and
      their parents. The younger sister with auditory canal atresia received a bone
      anchored hearing aid (Baha), a transcutaneous bone conduction hearing device,
      resulting in a good hearing outcome. CONCLUSIONS: Based on the results of
      haplotype analysis, we proved that the BO syndrome in these cases was caused by
      germinal mosaicism of the EYA1 gene in either the mother or father. We also
      demonstrated that the bone-conduction hearing implant is a good option for BO
      patients with complex outer, middle, and inner ear anomalies.

PMID- 25780254
TI  - Non-ocular Stickler syndrome with a novel mutation in COL11A2 diagnosed by
      massively parallel sequencing in Japanese hearing loss patients.
AB  - OBJECTIVES: This study aims to document the clinical features of patients with
      COL11A2 mutations and to describe the usefulness of massively parallel
      sequencing. METHODS: One thousand one hundred twenty (1120) Japanese hearing loss
      patients from 53 ENT departments nationwide participated in this study. Massively
      parallel sequencing of 63 genes implicated in hearing loss was performed to
      identify the genetic causes in the Japanese hearing loss patients. RESULTS: A
      novel mutation in COL11A2 (c.3937_3948delCCCCCAGGGCCA) was detected in an
      affected family, and it was segregated in all hearing loss individuals. The
      clinical findings of this family were compatible with non-ocular Stickler
      syndrome. Orofacial features of mid-facial hypoplasia and slowly progressive mild
      to moderate hearing loss were also presented. Audiological examinations showed
      favorable auditory performance with hearing aid(s). CONCLUSION: This is the first
      case report of the genetic diagnosis of a non-ocular Stickler syndrome family in
      the Japanese population. We suggest that it is important to take both genetic
      analysis data and clinical symptoms into consideration to make an accurate
      diagnosis.

PMID- 25780255
TI  - Parents' and children's beliefs and concerns about taking medicines.

PMID- 25780256
TI  - Primary Immunodeficiency Diseases: An Opportunity in Pediatrics for Improving
      Patient Outcomes.
AB  - OBJECTIVES: Primary immunodeficiency diseases (PIDDs) are caused by inherent
      deficits in immune defenses that result in abnormal susceptibility to infection.
      In most cases, early and appropriate diagnosis can improve patient outcomes. The
      objective of this study was to evaluate understanding, recognition, and diagnosis
      of PIDD among pediatricians. METHODS: A mail survey sent to a sample of
      pediatricians obtained from the American Medical Association and American
      Osteopathic Association. Results were compared with a similar survey of
      specialists who are members of the American Academy of Asthma, Allergy and
      Immunology. RESULTS: More than a third (35%) of pediatricians were uncomfortable
      with the recognition and diagnosis of PIDD despite 95% having ordered screening
      tests or referring patients to specialists to be evaluated for PIDD, and 77%
      having followed at leastone patient with PIDD. In all, 84% of pediatricians were
      unaware that professional guidelines for PIDD exist. CONCLUSIONS: Patients with
      PIDD would benefit from improved recognition of the diseases by pediatricians in
      order to facilitate earlier diagnosis and optimize ongoing therapy.

PMID- 25780257
TI  - The Burden of Psychosocial Stressors and Urgent Mental Health Problems in a
      Pediatric Weight Management Program.
AB  - OBJECTIVE: To systematically screen for behavioral and mental health problems and
      psychosocial stressors (PS) in newly referred patients and adult caregivers
      (PACs) in a pediatric weight management program. METHODS: We used the Strengths
      and Difficulties Questionnaire (SDQ), the Center for Epidemiologic Studies
      Depression Scale (CES-D) for caregivers and patients >=18 years, and assessed
      urgent mental health concerns and psychosocial stressors. RESULTS: A total of 243
      PACs were screened; data were unavailable for 6. Compared with US normative data
      for the SDQ-Parent Proxy Version, the proportion of patients in our sample with
      borderline/abnormal total difficulties and conduct problems scores was greater
      for all age groups. Among adult caregivers with complete CES-D, 18.4% were at
      risk for depression. Eleven percent of patients screened positive for urgent
      mental health problems. Overall, 43% of patients and 57.4% of caregivers had PS.
      CONCLUSIONS: Systematic screening identified untreated symptoms and significant
      PS. Addressing these complex problems likely requires collaborative approaches
      with community providers.

PMID- 25780258
TI  - The effectiveness of a neck and shoulder stretching exercise program among office
      workers with neck pain: a randomized controlled trial.
AB  - OBJECTIVE: To determine the effectiveness of neck and shoulder stretching
      exercises for relief neck pain among office workers. DESIGN: Randomized
      controlled trial. SETTING: An outpatient setting. PARTICIPANTS: A total of 96
      subjects with moderate-to-severe neck pain (visual analogue score ?5/10) for ?3
      months. INTERVENTIONS: All participants received an informative brochure
      indicating the proper position and ergonomics to be applied during daily work.
      The treatment group received the additional instruction to perform neck and
      around shoulder stretching exercises two times/day, five days/week during four
      weeks. MAIN OUTCOMES: Pain, neck functions, and quality of life were evaluated at
      baseline and week 4 using pain visual analogue scale, Northwick Park Neck Pain
      Questionnaire, and Short Form-36, respectively. RESULTS: Both groups had
      comparable baseline data. All outcomes were improved significantly from baseline.
      When compared between groups, the magnitude of improvement was significantly
      greater in the treatment group than in the control group (-1.4; 95% CI: -2.2, 
      0.7 for visual analogue scale; -4.8; 95% CI: -9.3, -0.4 for Northwick Park Neck
      Pain Questionnaire; and 14.0; 95% CI: 7.1, 20.9 for physical dimension of the
      Short Form-36). Compared with the patients who performed exercises <3 times/week,
      those who exercised ?3 times/week yielded significantly greater improvement in
      neck function and physical dimension of quality of life scores (p = 0.005 and p =
      0.018, respectively). CONCLUSION: A regular stretching exercise program performed
      for four weeks can decrease neck and shoulder pain and improve neck function and
      quality of life for office workers who have chronic moderate-to-severe neck or
      shoulder pain.

PMID- 25780259
TI  - Self-help relaxation for post-stroke anxiety: a randomised, controlled pilot
      study.
AB  - OBJECTIVE: To consider relaxation as a potential treatment for anxiety in stroke
      survivors living in the community, including feasibility and acceptability.
      DESIGN: Randomised two group design (intervention and control). PARTICIPANTS: All
      participants (n = 21) were stroke survivors living in the community who reported
      experiencing anxiety (Hospital Anxiety and Depression Scale - Anxiety Subscale ?
      6). INTERVENTIONS: The intervention group were asked to listen to a self-help
      autogenic relaxation CD, five times a week, for at least one month. Participants
      completed the Hospital Anxiety and Depression Scale at screening and then monthly
      for three months. RESULTS: At each assessment following screening, participants
      who received the relaxation training were significantly more likely to report
      reduced anxiety compared to those who had not received the training (Month 1 P =
      0.002; Month 2 P < 0.001; Month 3 P = 0.001). After one month, seven of the
      intervention group (n = 10) had completed the relaxation training as directed and
      planned to continue using it. The intervention appeared practical to deliver and
      relatively inexpensive, with minimal adverse effects. CONCLUSIONS: Preliminary
      evidence suggests that autogenic relaxation training delivered in a self-help CD
      format is a feasible and acceptable intervention, and that anxiety is reduced in
      stroke survivors who received the intervention. Future studies should seek to
      recruit a larger and more heterogeneous sample of 70 participants.

PMID- 25780260
TI  - The efficacy of three-dimensional Schroth exercises in adolescent idiopathic
      scoliosis: a randomised controlled clinical trial.
AB  - OBJECTIVE: To compare the efficacy of three-dimensional (3D) Schroth exercises in
      patients with adolescent idiopathic scoliosis. DESIGN: A randomised-controlled
      study. SETTING: An outpatient exercise-unit and in a home setting. SUBJECTS:
      Fifty-one patients with adolescent idiopathic scoliosis. INTERVENTIONS: Forty
      five patients with adolescent idiopathic scoliosis meeting the inclusion criteria
      were divided into three groups. Schroth's 3D exercises were applied to the first
      group in the clinic and were given as a home program for the second group; the
      third group was the control. MAIN MEASURES: Scoliosis angle (Cobb method), angle
      of rotation (scoliometer), waist asymmetry (waist - elbow distance), maximum hump
      height of the patients and quality of life (QoL) (SRS-23) were assessed pre
      treatment and, at the 6(th), 12(th) and 24(th) weeks. RESULTS: The Cobb (-2.53
      degrees ; P=0.003) and rotation angles (-4.23 degrees ; P=0.000) significantly
      decreased, which indicated an improvement in the clinic exercise group compared
      to the other groups. The gibbosity (-68.66mm; P=0.000) and waist asymmetry
      improved only in the clinic exercise group, whereas the results of the other
      groups worsened. QoL did not change significantly in either group. CONCLUSION:
      According to the results of this study the Schroth exercise program applied in
      the clinic under physiotherapist supervision was superior to the home exercise
      and control groups; additionally, we observed that scoliosis progressed in the
      control group, which received no treatment.

PMID- 25780261
TI  - Does wearing unstable shoes reduce low back pain and disability in nurses? A
      randomized controlled pilot study.
AB  - OBJECTIVE: To evaluate if wearing unstable shoes reduces low back pain and
      disability in nurses. DESIGN: A randomized controlled trial. SETTING: Hospitals
      and homecare. SUBJECTS: A total of 20 matched female registered nurses with low
      back pain. The mean (standard deviation) age was 31 years (5) for the control and
      34 years (6) for the intervention group; height was 161 cm (5) and 165 cm (7),
      respectively. INTERVENTIONS: The intervention group received unstable shoes at
      Week 2 to wear for at least 36 h/week for a month. MAIN MEASURES: The Oswestry
      Low Back Pain Disability Questionnaire and a visual analogue pain scale. RESULTS:
      The mean (standard deviation) pain level was 6 (1) at baseline vs. 6 (2) at Week
      6 for the control group, and 5 (1) vs. 1 (1) for the intervention group. The mean
      (standard deviation) disability level was 31% (9) at baseline vs. 28% (7) at Week
      6 for the control, and 27% (12) vs. 13% (5) for the intervention group. There
      were no significant changes over time on pain or disability levels for the
      control group. The intervention group reported lower levels of pain on Weeks 4
      (mean difference ?-1.4, p ? 0.009) and 6 (mean difference ?-3.1, p < 0.001).
      Disability levels were also lower on Weeks 4 (mean difference = -4.5%, p NS) and
      6 (mean difference = -14.1%, p = 0.020). CONCLUSIONS: Wearing unstable shoes
      reduced low back pain and disability in nurses and might be helpful as part of
      the back pain rehabilitation process.

PMID- 25780263
TI  - Psychogenic nonepileptic seizures: a new direction.

PMID- 25780262
TI  - Design and baseline characteristics of the CARdiovascular Outcome Trial of
      LINAgliptin Versus Glimepiride in Type 2 Diabetes (CAROLINA(r)).
AB  - CARdiovascular Outcome Trial of LINAgliptin Versus Glimepiride in Type 2 Diabetes
      (NCT01243424) is an ongoing, randomized trial in subjects with early type 2
      diabetes and increased cardiovascular risk or established complications that will
      determine the long-term cardiovascular impact of linagliptin versus the
      sulphonylurea glimepiride. Eligible patients were sulphonylurea-naive with HbA1c
      6.5%-8.5% or previously exposed to sulphonylurea (in monotherapy or in a
      combination regimen <5 years) with HbA1c 6.5%-7.5%. Primary outcome is time to
      first occurrence of cardiovascular death, non-fatal myocardial infarction, non
      fatal stroke or hospitalization for unstable angina. A total of 631 patients with
      primary outcome events will be required to provide 91% power to demonstrate non
      inferiority in cardiovascular safety by comparing the upper limit of the two
      sided 95% confidence interval as being below 1.3 for a given hazard ratio.
      Hierarchical testing for superiority will follow, and the trial has 80% power to
      demonstrate a 20% relative cardiovascular risk reduction. A total of 6041
      patients were treated with median type 2 diabetes duration 6.2 years, 40.0%
      female, mean HbA1c 7.2%, 66% on 1 and 24% on 2 glucose-lowering agents and 34.5%
      had previous cardiovascular complications. The results of CARdiovascular Outcome
      Trial of LINAgliptin Versus Glimepiride in Type 2 Diabetes may influence the
      decision-making process for selecting a second glucose-lowering agent after
      metformin in type 2 diabetes. 

PMID- 25780264
TI  - Autonomic changes in psychogenic nonepileptic seizures: toward a potential
      diagnostic biomarker?
AB  - Disturbances of the autonomic nervous system (ANS) are common in neuropsychiatric
      disorders. Disease specific alterations of both sympathetic and parasympathetic
      activity can be assessed by heart rate variability (HRV), whereas electrodermal
      activity (EDA) can assess sympathetic activity. In posttraumatic stress disorder
      (PTSD), parasympathetic HRV parameters are typically decreased and EDA is
      increased, whereas in major depressive disorder (MDD) and dissociation, both
      parasympathetic and sympathetic markers are decreased. ANS abnormalities have
      also been identified in psychogenic nonepileptic seizures (PNES) by using HRV,
      indicating lower parasympathetic activity at baseline. In addition to reviewing
      the current literature on ANS abnormalities in PTSD, MDD, and disorders with
      prominent dissociation, including borderline personality disorder (BPD), this
      article also presents data from a pilot study on EDA in patients with PNES.
      Eleven patients with PNES, during an admission to our epilepsy monitoring unit
      (EMU), were compared with 9 with generalized tonic-clonic seizures (GTCS). The
      area under the EDA curve, the number of EDA responses lasting longer than 2
      seconds, and the number of EDA surges during sleep (sympathetic sleep storms)
      were calculated on ictal and interictal days by an automated algorithm. EDA
      changes in PNES patients did not follow a systematic pattern of sympathetic
      hyperarousal (like EDA after GTCS) but were more variable. How specific PNES
      semiologies, and/or underlying neuropsychiatric disorders, may influence ictal
      and interictal EDA patterns, and lead to a novel diagnostic biomarker remains to
      be evaluated in future larger studies. 

PMID- 25780265
TI  - A clinically oriented perspective on psychogenic nonepileptic seizure-related
      emergencies.
AB  - Psychogenic nonepileptic seizures (PNES) can present emergently and are often
      mistaken for epileptic seizures. PNES emergencies have not been well studied, and
      yet there are associated serious morbidities, particularly when patients are seen
      in an emergency setting and are misdiagnosed. PNES may be prolonged, mimicking
      status epilepticus, a condition we refer to as nonepileptic psychogenic status
      (NEPS), and patients may receive aggressive and unnecessary medical treatments
      that can lead to serious iatrogenic complications, including death. NEPS is also
      associated with an increased risk of self-harm, including suicide attempts, and
      may indicate a serious comorbid psychiatric illness. In addition to iatrogenic
      complications of PNES, accidents and injuries are an underrecognized source of
      morbidity. PNES may also present during medical procedures, which may not only
      interfere with their completion, but may alarm practitioners who, fearing
      liability, may initiate further medical evaluations and treatments. When PNES
      occur during pregnancy, patients may be misdiagnosed with eclampsia and their
      offspring delivered prematurely. They also risk being placed on medications that
      are harmful to the fetus. Increased awareness of PNES is necessary to prevent
      iatrogenic harm and to identify underlying psychiatric illnesses that carry their
      own risks. As yet, data available to guide treatment are scant, and further study
      is needed. 

PMID- 25780266
TI  - Cognitive impairment and evaluation in psychogenic nonepileptic seizures: an
      integrated cognitive-emotional approach.
AB  - Neuropsychological studies comparing patients with psychogenic nonepileptic
      seizures (PNES) to those with epilepsy have been largely equivocal. The
      variability in the neuropsychological literature highlights the heterogeneity of
      the PNES population across a number of psychiatric and neurologic factors.
      Phenotypic presentations in PNES arise from complex interactions between
      vulnerable cognitive and emotional systems. We propose that variability in
      neuropsychological findings in PNES emerge in the context of diverse psychiatric,
      neurologic, and clinical factors. Traditional assessments that fail to integrate
      cognitive and emotional/behavioral profiles sufficiently would fall short in
      characterizing the complexity of brain-behavior relationships in this population.
      To advance the neuropsychology of PNES, we propose a systematic approach to
      measure a number of factors that influence cognitive impairment in this
      population. We begin by reviewing the current neuropsychological literature in
      PNES and discussing a number of factors that influence cognitive deficits. We
      then present a comprehensive neuropsychological battery designed to capture
      elements (cognitive dysfunction, psychopathology, emotion processing deficits)
      underlying the proposed vulnerable cognitive-emotional system in PNES. It is our
      hope that the proposed battery will facilitate the aggregation of data across
      neuropsychological investigations, to allow more advanced statistical analyses,
      and ultimately enhance our understanding of PNES and the development of effective
      management and treatment options. 

PMID- 25780267
TI  - High Rate of Recurrence Following Proximal Medial Opening Wedge Osteotomy for
      Correction of Moderate Hallux Valgus.
AB  - BACKGROUND: The proximal medial opening wedge (PMOW) osteotomy has become more
      popular to treat moderate to severe hallux valgus with the recent development of
      specifically designed, low-profile modular plates. Despite the promising results
      previously reported in the literature, we have noted a high incidence of
      recurrence in patients treated with a PMOW. The purpose of this study was to
      report the clinical and radiographic outcomes of an initial cohort of patients
      treated with a PMOW osteotomy for moderate hallux valgus. METHODS: We
      retrospectively analyzed prospectively gathered data on a cohort of 17
      consecutive patients who were treated by the senior author using a PMOW osteotomy
      for moderate hallux valgus deformity. Average time to follow-up was 2.4 years
      (range, 1.0-3.5 years). The intermetatarsal angle (IMA), the hallux valgus angle
      (HVA), and the distal metatarsal articular angle (DMAA) were assessed on standard
      weightbearing radiographs of the foot preoperatively and at all follow-up visits.
      The Foot and Ankle Outcome Score (FAOS) was collected on all patients
      preoperatively and at final follow-up. RESULTS: Despite demonstrating good
      correction of their deformity initially, 11 of the 17 patients (64.7%) had
      evidence of recurrence of their hallux valgus deformity at final follow-up.
      Patients who recurred had a greater preoperative HVA (P = .023) and DMAA (P =
      .049) than patients who maintained their correction. Improvement in the quality
      of-life subscale of the FAOS was noted at final follow-up for all patients (P =
      .05). There was no significant improvement in any of the other FAOS subscales.
      CONCLUSIONS: There was a high rate of recurrence of the hallux valgus deformity
      in this cohort of patients. Recurrence was associated with greater preoperative
      deformity and an increased preoperative DMAA. The PMOW without a concomitant
      distal metatarsal osteotomy may be best reserved for patients with mild hallux
      valgus deformity without an increased DMAA. LEVEL OF EVIDENCE: Level IV,
      retrospective case series.

PMID- 25780268
TI  - Advanced hallux rigidus: do we have a choice other than arthrodesis?

PMID- 25780269
TI  - Peripheral androgen action helps modulate vocal production in a suboscine
      passerine.
AB  - Androgenic activation of intracellular androgen receptors (AR) influences avian
      vocal production, though this has largely been investigated at the level of the
      brain. We investigated the influence of predominantly peripheral AR on vocal
      output in wild Golden-collared Manakins (Manacus vitellinus). In this suboscine
      species, males court females by performing acrobatic displays and by producing
      relatively simple chee-poo vocalizations. To assess whether peripheral AR
      influences the acoustic structure of these vocal signals, we treated
      reproductively active adult males with the peripherally selective antiandrogen
      bicalutamide and then measured phonation performance. Inhibiting AR outside of
      the central nervous system increased the duration of the chee note and decreased
      the fundamental frequency of the poo note. This treatment caused no discernable
      change to chee-poo frequency modulation or entropy. Our results show that
      activation of peripheral AR mediates note-specific changes to temporal and pitch
      characteristics of the Golden-collared Manakin's main sexual call. Thus, our
      study provides one of the first demonstrations that androgenic action originating
      outside of the brain and likely on musculoskeletal targets can modulate avian
      vocal production.

PMID- 25780270
TI  - Multi-walled carbon nanotube length as a critical determinant of bioreactivity
      with primary human pulmonary alveolar cells.
AB  - Multiwalled carbon nanotube (MWCNT) length is suggested to critically determine
      their pulmonary toxicity. This stems from in vitro and in vivo rodent studies and
      in vitro human studies using cell lines (typically cancerous). There is little
      data using primary human lung cells. We addressed this knowledge gap, using
      highly relevant, primary human alveolar cell models exposed to precisely
      synthesized and thoroughly characterized MWCNTs. In this work, transformed human
      alveolar type-I-like epithelial cells (TT1), primary human alveolar type-II
      epithelial cells (ATII) and alveolar macrophages (AM) were treated with
      increasing concentrations of MWCNTs before measuring cytotoxicity, inflammatory
      mediator release and MAP kinase signalling. Strikingly, we observed that short
      MWCNTs (~0.6 um in length) induced significantly greater responses from the
      epithelial cells, whilst AM were particularly susceptible to long MWCNTs (~20
      um). These differences in the pattern of mediator release were associated with
      alternative profiles of JNK, p38 and ERK1/2 MAP kinase signal transduction within
      each cell type. This study, using highly relevant target human alveolar cells and
      well defined and characterized MWCNTs, shows marked cellular responses to the
      MWCNTs that vary according to the target cell type, as well as the aspect ratio
      of the MWCNT.

PMID- 25780271
TI  - Optimization of a lensless digital holographic otoscope system for transient
      measurements of the human tympanic membrane.
AB  - In this paper, we propose a multi-pulsed double exposure (MPDE) acquisition
      method to quantify in full-field-of-view the transient (i.e., >10 kHz)
      acoustically induced nanometer scale displacements of the human tympanic membrane
      (TM or eardrum). The method takes advantage of the geometrical linearity and
      repeatability of the TM displacements to enable high-speed measurements with a
      conventional camera (i.e., <20 fps). The MPDE is implemented on a previously
      developed digital holographic system (DHS) to enhance its measurement
      capabilities, at a minimum cost, while avoiding constraints imposed by the
      spatial resolutions and dimensions of high-speed (i.e., >50 kfps) cameras. To our
      knowledge, there is currently no existing system to provide such capabilities for
      the study of the human TM. The combination of high temporal (i.e., >50 kHz) and
      spatial (i.e., >500k data points) resolutions enables measurements of the
      temporal and frequency response of all points across the surface of the TM
      simultaneously. The repeatability and accuracy of the MPDE method are verified
      against a Laser Doppler Vibrometer (LDV) on both artificial membranes and ex-vivo
      human TMs that are acoustically excited with a sharp (i.e., <100 MUs duration)
      click. The measuring capabilities of the DHS, enhanced by the MPDE acquisition
      method, allow for quantification of spatially dependent motion parameters of the
      TM, such as modal frequencies, time constants, as well as inferring local
      material properties.

PMID- 25780272
TI  - 16SrRNA sequencing of Dye decolorizing bacteria isolated from Soil.
AB  - Dye's residues in textile effluents are hazardous for humans and animals health.
      Such pollutants can be degraded into non-harmful molecules using biological
      approaches that are considered cheaper and ecologically safer. Isolated 15
      bacterial cultures from soil that could be used in biological system were showed
      decolorization capacity for Acid Green dye (33.9% to 94.0%) using thin layer
      chromatography and broth culture method. The most promising cultures (AMC3) to
      decolorize Acid green Dye (94.6%) was re-coded as NSDSUAM for submitting at
      IMTECH, Chandigarh for sequencing. The 16SrRNA sequencing suggested that it can
      be a variant of Pseudomonas geniculata (99.85% identical similarity) with
      difference of 2 base pairs to reference strain Pseudomonas geniculata ATCC
      19374(T). Thus present study proposed dye decolorizing efficiency of the isolated
      strain of Pseudomonas geniculata that was previously unnoticed. The sequence is
      deposited in NCBI GenBank with the accession number KP238100. 

PMID- 25780273
TI  - Handling class imbalance problem in miRNA dataset associated with cancer.
AB  - MiRNAs are small (~22nt long) non-coding RNA sequences; binds to the
      complementarity target sites in 3' Untranslated Region (UTR) of mRNA sequences
      but not restricted to other mRNA regions viz., 5' UTR and Coding sequences (CDS).
      Complementarity binding of miRNA to mRNA target sites either results in complete
      degradation of the mRNA itself or it may regulate the mRNA as an oncogene or as a
      tumor suppressor gene. However, the exact mechanism involved in identifying a
      miRNA to be associated with cancer is still unclear. Further, with the outburst
      in the number of miRNAs sequences recorded every year in miRBase, the gap is
      still widening mainly due to the laborious and economically unfavorable
      experimental procedures associated with the functional annotation. Motivated by
      the fact, we constructed a two-step support vector machine-based predictive model
      - miRSEQ and miRINT. However, the major pitfall during the construction of the
      model is the class imbalance problem. Hence, in order to overcome class imbalance
      problem, in the present study we empirically compare the effectiveness of two
      different methods viz., Synthetic Minority Oversampling Technique (SMOTE) and
      cost-senstive learning method. Performance measures were evaluated in terms of
      Precision and Recall. Based on our result, it was observed that for miRNA dataset
      with high class imbalance utilized for predicting association of cancer, cost
      sensitive method outperformed the oversampling method. 

PMID- 25780274
TI  - Structure and functional annotation of hypothetical proteins having putative
      Rubisco activase function from Vitis vinifera.
AB  - Rubisco is a very large, complex and one of the most abundant proteins in the
      world and comprises up to 50% of all soluble protein in plants. The activity of
      Rubisco, the enzyme that catalyzes CO2 assimilation in photosynthesis, is
      regulated by Rubisco activase (Rca). In the present study, we searched for
      hypothetical protein of Vitis vinifera which has putative Rubisco activase
      function. The Arabidopsis and tobacco Rubisco activase protein sequences were
      used as seed sequences to search against Vitis vinifera in UniprotKB database.
      The selected hypothetical proteins of Vitis vinifera were subjected to sequence,
      structural and functional annotation. Subcellular localization predictions
      suggested it to be cytoplasmic protein. Homology modelling was used to define the
      three-dimensional (3D) structure of selected hypothetical proteins of Vitis
      vinifera. Template search revealed that all the hypothetical proteins share more
      than 80% sequence identity with structure of green-type Rubisco activase from
      tobacco, indicating proteins are evolutionary conserved. The homology modelling
      was generated using SWISS-MODEL. Several quality assessment and validation
      parameters computed indicated that homology models are reliable. Further,
      functional annotation through PFAM, CATH, SUPERFAMILY, CDART suggested that
      selected hypothetical proteins of Vitis vinifera contain ATPase family associated
      with various cellular activities (AAA) and belong to the AAA+ super family of
      ring-shaped P-loop containing nucleoside triphosphate hydrolases. This study will
      lead to research in the optimization of the functionality of Rubisco which has
      large implication in the improvement of plant productivity and resource use
      efficiency. 

PMID- 25780275
TI  - Genome-wide identification of antimicrobial peptides in the liver fluke,
      Clonorchis sinensis.
AB  - The increase in prevalence of antimicrobial resistance makes the search for new
      antibiotic agents imperative. Antimicrobial peptides (AMPs) from natural
      resources have been recognized as suitable tools to combat antibiotic-resistant
      bacteria. The liver fluke Clonorchis sinensis living in germ-filled environments
      could be a good source of antimicrobials. Here, we report the use of a rational
      protocol that combines AMP predictions based on their physicochemical properties
      and their in vivo stability to discover AMP candidates from the entire genome of
      C. sinensis. To screen AMP candidates, in silico analyses based on the
      physicochemical properties of known AMPs, such as length, charge, isoelectric
      point, and in vitro and in vivo aggregation values were performed. To enhance
      their in vivo stability, proteins having proteolytic cleavage sites were
      excluded. As a consequence, four high-activity, highstability peptides were
      identified. These peptides could be potential starting materials for the
      development of new AMPs via structural modification and optimization. Thus, this
      study proposes a refined computational method to develop new AMPs and identifies
      four AMP candidates, which could serve as templates for further development of
      peptide antibiotics. 

PMID- 25780276
TI  - Identification of Ellagic acid analogues as potent inhibitor of protein Kinase
      CK2:A chemopreventive role in oral Cancer.
AB  - Over expression of Protein kinase (CK2) suppresses apoptosis induced by a variety
      of agents, whereas down-regulation of CK2 sensitizes cells to induction of
      apoptosis. In this study, we have built quantitative structure activity
      relationship (QSAR) models, which were trained and tested on experimentally
      verified 38 enzyme's inhibitors having inhibitory value IC50 in uM. These
      inhibitors were docked at the active site of CK2 (PDB id: 2ZJW) using AutoDock
      software, which resulted in energy-based descriptors such as binding energy,
      intermol energy, torsional energy, internal energy and docking energy. For QSAR
      modeling, Multiple Linear Regression (MLR) model was engendered using energy
      based descriptors yielding correlation coefficient r(2) of 0.4645. To assess the
      predictive performance of QSAR models, different cross-validation procedures were
      adopted. Our results suggests that ligand-receptor binding interactions for CK2
      employing QSAR modeling seems to be a promising approach for prediction of IC50
      value of a new ligand molecule against CK2.Further, twenty analogues of ellagic
      acid were docked with CK2 structure. After docking, two compounds CID 46229200
      and CID 10003463 had lower docking energy even lower than standard control
      Ellagic acid with CK2 was selected as potent candidate drugs for Oral cancer. The
      biological activity of two compounds in terms of IC50 was predicted based on QSAR
      model, which could be used as a guideline for anticancerous activity of compounds
      before their synthesis. 

PMID- 25780277
TI  - A novel feature extraction approach for microarray data based on multi-algorithm
      fusion.
AB  - Feature extraction is one of the most important and effective method to reduce
      dimension in data mining, with emerging of high dimensional data such as
      microarray gene expression data. Feature extraction for gene selection, mainly
      serves two purposes. One is to identify certain disease-related genes. The other
      is to find a compact set of discriminative genes to build a pattern classifier
      with reduced complexity and improved generalization capabilities. Depending on
      the purpose of gene selection, two types of feature extraction algorithms
      including ranking-based feature extraction and set-based feature extraction are
      employed in microarray gene expression data analysis. In ranking-based feature
      extraction, features are evaluated on an individual basis, without considering
      inter-relationship between features in general, while set-based feature
      extraction evaluates features based on their role in a feature set by taking into
      account dependency between features. Just as learning methods, feature extraction
      has a problem in its generalization ability, which is robustness. However, the
      issue of robustness is often overlooked in feature extraction. In order to
      improve the accuracy and robustness of feature extraction for microarray data, a
      novel approach based on multi-algorithm fusion is proposed. By fusing different
      types of feature extraction algorithms to select the feature from the samples
      set, the proposed approach is able to improve feature extraction performance. The
      new approach is tested against gene expression dataset including Colon cancer
      data, CNS data, DLBCL data, and Leukemia data. The testing results show that the
      performance of this algorithm is better than existing solutions. 

PMID- 25780278
TI  - Analysis of expressed sequence tags from cDNA library of Fusarium culmorum
      infected barley (Hordeum vulgare L.) roots.
AB  - Fusarium culmorum is one of the most common and globally important causal agent
      of root and crown rot diseases of cereals. These diseases cause grain yield loss
      and reduced grain quality in barley. In this study, we have analyzed an expressed
      sequence tag (EST) database derived from F. culmorum infected barley root tissues
      available at the National Center for Biotechnology Information (NCBI). The 2294
      sequences were assembled into 1619 non-redundant sequences consisting of 359
      contigs and 1260 singletons using the program CAP3. BLASTX analysis for these
      sequences was conducted in order to find similar sequences in all databases. Gene
      Ontology search, enzyme search, KEGG mapping and InterProScan search were done
      using Blast2GO 3.0.7 tool. By BLASTX analysis, 41.7%, 7.7%, 3.2% and 47.4% of
      ESTs were categorized as annotated, unannotated, not mapping and without blast
      hits, respectively. BLASTX analysis revealed that the majority of top hits were
      barley proteins (43.5%). Based on Gene Ontology classification, 38.3%, 31.3%, and
      16% of ESTs were assigned to molecular function, biological process, and cellular
      component GO terms, respectively. Most abundant GO terms were as follows: 157
      sequences were related to response to stress (biological process), 207 sequences
      were related to ion binding (molecular function), and 160 sequences were related
      to plastid (cellular component). Furthermore, based on KEGG mapping, 369
      sequences could be assigned to 264 enzymes and 83 different KEGG pathways.
      According to Enzyme Commission (EC) distribution; 94 sequences were transferases
      (EC2) while 70 sequences were hydrolases (EC3). 

PMID- 25780279
TI  - SBION2: Analyses of Salt Bridges from Multiple Structure Files, Version 2.
AB  - Specific electrostatics (i.e. salt-bridge) includes both local and non-local
      interactions that contribute to the overall stability of proteins. It has been
      shown that a salt-bridge could either be buried or exposed, networked or
      isolated, hydrogen-bonded or nonhydrogen bonded, in secondary-structure or in
      coil, formed by single or multiple bonds. Further it could also participates
      either in intra- or inter-dipole interactions with preference in orientation
      either for basic residue at N-terminal (orientation-I) or acidic residue at N
      terminal (orientation-II). In this context SBION2 is unique in that it reports
      above mentioned binary items in excel format along with details on intra and
      inter-dipole interactions and orientations. These results are suitable for post
      run statistical analyses involving large datasets. Reports are also made on
      protein-protein interactions, intervening residue distances and general residue
      specific salt-bridge details. A ready to use compact supplementary table is also
      produced. The program runs in three alternative modes. Each mode works on any
      number of structure files with any number of chains at any given atomic distance
      of ion-pair. Thus SBION2 provides intricate details on salt-bridges and finds
      application in structural bioinformatics. AVAILABILITY: SBION2 is freely
      available at http://sourceforge.net/projects/sbion2/ for academic users.

PMID- 25780280
TI  - Disease associated cellular machinery in anaphylaxis - And the de novo paradigm
      shift.
AB  - Anaphylaxis is a sudden immune reaction against an allergen that can potentially
      lead to Anaphylactic Shock (AS). This immune reaction is characterized by an
      increase in Immunoglobulin-E (IgE) type of antibodies that bind with FcepsilonRI
      receptors on mast cells to release inflammatory mediators. Various intracellular
      signaling molecules downstream of IgE/ FcepsilonRI axis play a potential role in
      cytokine, chemokine and eicosanoid secretion as well as degranulation of immune
      cells causing vasodilation, vascular permeability, and reduction of intravascular
      volume leading to cardiovascular collapse. Here, we discuss the cellular
      machinery of anaphylaxis and the de novo paradigm shift in the cellular aspects
      of AS. 

PMID- 25780281
TI  - Viral immune surveillance: Toward a TH17/TH9 gate to the central nervous system.
AB  - Viral cellular immune surveillance is a dynamic and fluid system that is driven
      by finely regulated cellular processes including cytokines and other factors
      locally in the microenvironment and systemically throughout the body. It is
      questionable as to what extent the central nervous system (CNS) is an immune
      privileged organ protected by the blood-brain barrier (BBB). Recent evidence
      suggests converging pathways through which viral infection, and its associated
      immune surveillance processes, may alter the integrity of the blood-brain
      barrier, and lead to inflammation, swelling of the brain parenchyma and
      associated neurological syndromes. Here, we expand upon the recent "gateway
      theory", by which viral infection and other immune activation states may disrupt
      the specialized tight junctions of the BBB endothelium making it permeable to
      immune cells and factors. The model we outline here builds upon the proposition
      that this process may actually be initiated by cytokines of the IL-17 family, and
      recognizing the intimate balance between TH17 and TH9 cytokine profiles
      systemically. We argue that immune surveillance events, in response to viruses
      such as the Human Immunodeficiency Virus (HIV), cause a TH17/TH9 induced gateway
      through blood brain barrier, and thus lead to characteristic neuroimmune
      pathology. It is possible and even probable that the novel TH17/TH9 induced
      gateway, which we describe here, opens as a consequence of any state of immune
      activation and sustained chronic inflammation, whether associated with viral
      infection or any other cause of peripheral or central neuroinflammation. This
      view could lead to new, timely and critical patient-centered therapies for
      patients with neuroimmune pathologies across a variety of etiologies.
      ABBREVIATIONS: BBB - blood brain barrier, BDV - Borna disease virus, CARD -
      caspase activation and recruitment domains, CD - clusters of differentiation, CNS
      - central nervous system, DAMP - damage-associated molecular patterns, DENV -
      Dengue virus, EBOV - Ebola virus, ESCRT - endosomal sorting complex required for
      transport-I, HepC - Hepatitis C virus, HIV - human immunodeficiency virus, IFN -
      interferon, ILn - interleukin-n, IRF-n - interferon regulatory factor-n, MAVS -
      mitochondrial antiviral-signaling, MBGV - Marburg virus, M-CSF - macrophage
      colony-stimulating factor, MCP-1 - monocyte chemotactic protein 1 (aka CCL2), MHC
      - major histocompatibility complex, MIP-alpha beta - macrophage inflammatory
      protein-1 alpha beta (aka CCL3 & CCL4), MIF - macrophage migration inhibitory
      factor, NVE - Nipah virus encephalitis, NK - natural killer cell, NLR - NLR, NOD 
      like receptor, NOD - nucleotide oligomerization domain, PAMP - pathogen
      associated molecular patterns, PtdIns - phosphoinositides, PV - Poliovirus, RIG-I
      - retinoic acid-inducible gene I, RIP - Receptor-interacting protein (RIP)
      kinase, RLR - RIG-I-like receptor, sICAM1 - soluble intracellular adhesion
      molecule 1, STAT-3 - signal tranducer and activator of transcription-3, sVCAM1 -
      soluble vascular cell adhesion molecule 1, TANK - TRAF family member-associated
      NF- . B activator, TBK1 - TANK-binding kinase 1, TLR - Toll-like receptor, TNF -
      tumor necrosis factor, TNFR - TNF receptor, TNFRSF21 - tumor necrosis factor
      receptor superfamily member 21, TRADD TNFR-SF1A - associated via death domain,
      TRAF TNFR - associated factor, Tregs - regulatory T cellsubpopulation
      (CD4/8+CD25+FoxP3+), VHF - viral hemorrhagic fever.

PMID- 25780282
TI  - Mesopancreas: A boundless structure, namely the rationale for dissection of the
      paraaortic area in pancreaticoduodenectomy for pancreatic head carcinoma.
AB  - This review highlights the rationale for dissection of the 16a2 and 16b1
      paraaortic area during pancreaticoduodenectomy (PD) for carcinoma of the head of
      the pancreas. Recent advances in surgical anatomy of the mesopancreas indicate
      that the retropancreatic area is not a single entity with well defined boundaries
      but an anatomical site of embryological fusion of peritoneal layers, and that
      continuity exists between the neuro lymphovascular adipose tissues of the
      retropancreatic and paraaortic areas. Recent advances in surgical pathology and
      oncology indicate that, in pancreatic head carcinoma, the mesopancreatic
      resection margin is the primary site for R1 resection, and that epithelial
      mesenchymal transition-related processes involved in tumor progression may impact
      on the prevalence of R1 resection or local recurrence rates after R0 surgery.
      These concepts imply that mesopancreas resection during PD for pancreatic head
      carcinoma should be extended to the paraaortic area in order to maximize
      retropancreatic clearance and minimize the likelihood of an R1 resection or the
      persistence of residual tumor cells after R0 resection. In PD for pancreatic head
      carcinoma, the rationale for dissection of the paraaortic area is to control the
      spread of the tumor cells along the mesopancreatic resection margin, rather than
      to control or stage the nodal spread. Although mesopancreatic resection cannot be
      considered "complete" or "en bloc", it should be "extended as far as possible" or
      be "maximal", including dissection of 16a2 and 16b1 paraaortic areas. 

PMID- 25780283
TI  - Targeted therapy in first line treatment of RAS wild type colorectal cancer.
AB  - The debate on the optimal drug combination for treating chemotherapy-naive
      patients with metastatic colorectal cancer has recently become particularly
      heated. The present editorial will review recent data on this topic. The FIRE-3
      and PEAK trials have shown a 7.5 to 12 mo survival advantage with the use anti
      epidermal growth factor receptor (anti-EGFR) antibodies. The CALGB 80405 has
      shown no difference between anti-EGFR and anti-vascular endothelial growth factor
      agents. All three trials have consistently shown a significant increase in
      objective response rate. These data suggest that there is a subset of metastatic
      colorectal cancer patients, rigorously selected by molecular profiling, who
      particularly benefit from an anti-EGFR-based regimen in the first-line setting. 

PMID- 25780284
TI  - Chemokine ligand 2 and paraoxonase-1 in non-alcoholic fatty liver disease: The
      search for alternative causative factors.
AB  - The incidence and prevalence of non-alcoholic fatty liver disease (NAFLD) is
      constantly increasing. Despite this is apparently associated with the growing
      increase in obesity, insulin resistance and obesity-related metabolic
      disturbances their presence is not a necessary or sufficient condition to explain
      the accumulation of fat in the liver. Conversely, NAFLD is a predictor of other
      metabolic risks. NAFLD is currently the most frequent chronic liver disease but
      should not be considered benign or anecdotic because a considerable proportion of
      patients with NAFLD progress to cirrhosis and end-stage liver disease.
      Consequently, the search for alternative molecular mechanisms with therapeutic
      implications in NAFLD and associated disorders deserves a careful consideration.
      Mitochondria are possible targets as these organelles generate energy from
      nutrient oxidation. Some findings, generated in patients with extreme obesity and
      in murine models, support the notion that NAFLD could be a mitochondrial disease.
      This is plausible because mitochondrial dysfunction affects the accumulation of
      lipids in hepatocytes and promotes lipid peroxidation, the production of reactive
      oxygen species, the release of cytokines causing inflammation and cell death.
      Here we discuss basic research and mechanistic studies targeting the role of
      chemokine ligand 2 in liver inflammation and that of the paraoxonases in the
      oxidative stress. Their combination and association with mitochondrial
      dysfunction may uncover mechanisms underlying the progression of NAFLD and may
      help to identify novel therapeutic targets. 

PMID- 25780285
TI  - To be or not to be: The host genetic factor and beyond in Helicobacter pylori
      mediated gastro-duodenal diseases.
AB  - Helicobacter pylori (H. pylori) have long been associated with a spectrum of
      disease outcomes in the gastro-duodenal system. Heterogeneity in bacterial
      virulence factors or strains is not enough to explain the divergent disease
      phenotypes manifested by the infection. This review focuses on host genetic
      factors that are involved during infection and eventually are thought to
      influence the disease phenotype. We have summarized the different host genes that
      have been investigated for association studies in H. pylori mediated duodenal
      ulcer or gastric cancer. We discuss that as the bacteria co-evolved with the
      host; these host gene also show much variation across different ethnic
      population. We illustrate the allelic distribution of interleukin-1B, across
      different population which is one of the most popular candidate gene studied with
      respect to H. pylori infections. Further, we highlight that several polymorphisms
      in the pathway gene can by itself or collectively affect the acid secretion
      pathway axis (gastrin: somatostatin) thereby resulting in a spectrum of disease
      phenotype. 

PMID- 25780286
TI  - Endoscopic and histologic characteristics of serrated lesions.
AB  - In recent years, a second pathway for colonic carcinogenesis, distinct from the
      adenomatous pathway, has been explored. This is referred to as serrated pathway
      and includes three types of polyp, characterised by a serrated appearance of the
      crypts: hyperplastic polyps (HP), sessile serrated adenomas (SSA) or lesions, and
      traditional serrated adenomas. Each lesion has its own genetic, as well as
      macroscopic and microscopic morphological features. Because of their flat aspect,
      their detection is easier with chromoendoscopy (carmin indigo or narrow-band
      imaging). However, as we show in this review, the distinction between SSA and HP
      is quite difficult. It is now recommended to resect in one piece as it is
      possible the serrated polyps with a control in a delay depending on the presence
      or not of dysplasia. These different types of lesion are described in detail in
      the present review in general population, in polyposis and in inflammatory bowel
      diseases patients. This review highlights the need to improve characterization
      and understanding of this way of colorectal cancerogenesis. 

PMID- 25780287
TI  - Prevalence of human papillomavirus in esophageal carcinoma in Tangshan, China.
AB  - AIM: To study the prevalence of human papillomavirus (HPV) in esophageal
      carcinoma in Tangshan, China, a high-incidence area. METHODS: Formalin-fixed,
      paraffin-embedded tissue specimens from 198 patients who were pathologically
      diagnosed with esophageal squamous cell carcinoma from 2011 to 2013 were obtained
      from a pathology department in Tangshan. DNA was extracted from all 198 specimens
      to detect HPV by polymerase chain reaction (PCR). beta-globin PCR was performed
      to check the quality of the DNA extraction procedure. PCR was performed to detect
      a wide range of HPV types, and type-specific PCR was performed to detect HPV
      types 16 and 18. Negative and positive controls were used for HPV 16 and 18
      detection. RESULTS: The DNA extraction method in this study appeared to be more
      effective than other previously reported methods. After DNA extraction, more than
      98% of the tissue specimens had an acceptable result in the DNA qualification
      test (beta-globin PCR). The overall prevalence of HPV in tumor tissues by
      GP6+/GP5+ PCR was 79.79%, and the prevalence of HPV types 16 and 18 was 40.40%
      and 47.47%, respectively. PCR demonstrated the presence of HPV, and direct
      sequencing confirmed the HPV genotypes. All HPV-positive PCR products were
      checked by DNA sequence analysis using DNAman and compared with the known HPV
      sequences listed in the Basic Local Alignment Search Tool database to evaluate
      the HPV types. This analysis confirmed the presence of HPV types 16 and 18.
      CONCLUSION: DNA of high-risk HPV types 16 and 18 is present in esophageal tumors,
      implicating HPV as a possible etiologic factor for esophageal squamous cell
      carcinoma.

PMID- 25780288
TI  - Inhibitory effect of TongXie-YaoFang formula on colonic contraction in rats.
AB  - AIM: To investigate the pharmacological effect of TongXie-YaoFang (TXYF) formula
      and its underlying mechanisms. METHODS: A neonatal maternal separation plus
      restraint stress (NMS + RS) model of diarrhea-predominant irritable bowel
      syndrome was developed by subjecting male Sprague-Dawley rats to daily maternal
      separation from postnatal days 2 to 21 plus restraint stress from days 50 to 59.
      Rats were randomly divided into two groups (NMS + RS and TXYF formula), and rats
      with no handling or separation were used as normal controls. Starting from
      postnatal day 60, rats were administered TXYF formula (9.84 g/100 g body weight)
      orally twice daily for 14 consecutive days, while the normal and NMS + RS groups
      were given distilled water. The distinctions of movement index (MI, area under
      the curve of contraction intensity/min, mg/min) and contraction frequency (CF,
      number of contractions/min, times/min) of isolated colonic longitudinal smooth
      muscle strips (CLSMs) in the three groups before and after treatment were
      observed with a Power Lab system. Different inhibitors were applied, and then 10(
      4) mol/L acetylcholine chloride (Ach) was added to CLSMs to induce muscle
      contraction. RESULTS: Before treatment, the MI of CLSMs in the NMS + RS and TXYF
      formula groups was similar and both higher than that in the normal group (545.49
      +/- 73.66 mg/min vs 245.76 +/- 34.44 mg/min and 551.09 +/- 54.29 mg/min vs 245.76
      +/- 34.44 mg/min, P < 0.01, respectively). After treatment, the MI in the TXYF
      formula group was lower than that in the NMS + RS group (261.39 +/- 38.59 mg/min
      vs 533.9 +/- 61.63 mg/min, P < 0.01). In the same way, the CF of CLSMs in the NMS
      + RS and TXYF formula groups was similar and both higher than that in the normal
      group (3.42 +/- 0.25 times/min and 3.31 +/- 0.21 vs 1.1 +/- 0.17 times/min, P <
      0.01) before treatment. After treatment, the CF in the TXYF formula group was
      lower than that in the NMS + RS group (1.42 +/- 0.87 times/min vs 3.11 +/- 0.82
      times/min, P < 0.01) and similar to that in the normal group (1.42 +/- 0.87
      times/min vs 1.09 +/- 0.13 times/min). When 8-(N,N-diethylamino)octyl 3,4,5
      trimethoxybenzoate hydrochloride and 4-aminopyridine were added to the bath and
      equilibrated for 30 min, respectively, and 10(-4) mol/L Ach was added to CLSMs to
      induce muscle contraction, MI of the CLSMs in the TXYF formula group was lower
      than that in the normal group (666 +/- 36.32 mg/min vs 747.77 +/- 49.47 mg/min,
      and 686.53 +/- 39.17 mg/min vs 750.45 +/- 29.39 mg/min; P < 0.01, respectively).
      The MI of CLSMs in the TXYF formula group was lower than that in the normal group
      after treatment with nifedipine (689.48 +/- 30.84 mg/min vs 741.65 +/- 32.41
      mg/min; P < 0.05). CONCLUSION: TXYF formula inhibits colon contraction in rats.
      This may be related to activation of specific potassium channels and inhibition
      of extracellular calcium internal flow.

PMID- 25780289
TI  - Improved method increases sensitivity for circulating hepatocellular carcinoma
      cells.
AB  - AIM: To improve an asialoglycoprotein receptor (ASGPR)-based enrichment method
      for detection of circulating tumor cells (CTCs) of hepatocellular carcinoma
      (HCC). METHODS: Peripheral blood samples were collected from healthy subjects,
      patients with HCC or various other cancers, and patients with hepatic lesions or
      hepatitis. CTCs were enriched from whole blood by extracting CD45-expressing
      leukocytes with monoclonal antibody coated-beads following density gradient
      centrifugation. The remaining cells were cytocentrifuged on polylysine-coated
      slides. Isolated cells were treated by triple immunofluorescence staining with
      CD45 antibody and a combination of antibodies against ASGPR and carbamoyl
      phosphate synthetase 1 (CPS1), used as liver-specific markers, and costained with
      DAPI. The cell slide was imaged and stained tumor cells that met preset criteria
      were counted. Recovery, sensitivity and specificity of the detection methods were
      determined and compared by spiking experiments with various types of cultured
      human tumor cell lines. Expression of ASGPR and CPS1 in cultured tumor cells and
      tumor tissue specimens was analyzed by flow cytometry and triple
      immunofluorescence staining, respectively. RESULTS: CD45 depletion of leukocytes
      resulted in a significantly greater recovery of multiple amounts of spiked HCC
      cells than the ASGPR(+) selection (Ps < 0.05). The expression rates of either
      ASGPR or CPS1 were different in various liver cancer cell lines, ranging between
      18% and 99% for ASGPR and between 9% and 98% for CPS1. In both human HCC tissues
      and liver cancer cell lines, there were a few HCC cells that did not stain
      positive for ASGPR or CPS1. The mixture of monoclonal antibodies against ASGPR
      and CPS1 identified more HCC cells than either antibody alone. However, these
      antibodies did not detect any tumor cells in blood samples spiked with the human
      breast cancer cell line MCF-7 and the human renal cancer cell line A498. ASGPR(+)
      or/and CPS1(+) CTCs were detected in 29/32 (91%) patients with HCC, but not in
      patients with any other kind of cancer or any of the other test subjects.
      Furthermore, the improved method detected a higher CTC count in all patients
      examined than did the previous method (P = 0.001), and consistently achieved 12%
      21% higher sensitivity of CTC detection in all seven HCC patients with more than
      40 CTCs. CONCLUSION: Negative depletion enrichment combined with identification
      using a mixture of antibodies against ASGPR and CPS1 improves sensitivity and
      specificity for detecting circulating HCC cells.

PMID- 25780290
TI  - Anti-proliferation effects of Twist gene silencing in gastric cancer SGC7901
      cells.
AB  - AIM: To study the role of Twist gene in gastric cancer by gene silencing,
      including the potential of induction of apoptosis, cell cycle arrest, and
      proliferation inhibition in human malignant gastric SGC7901 cells. METHODS: The
      expression level of Twist in gastric cancer samples was measured by
      immunohistochemistry. The effects of Twist gene silencing were detected at both
      mRNA and protein levels by RT-PCR and Western blot. We also evaluated the cell
      proliferation and apoptosis by CCK-8 assay and flow cytometry. We determined the
      activity of caspase-3 and caspase-9 with a caspase activity assay kit. Cell cycle
      distribution was analyzed by flow cytometry. Cell migration and invasion ability
      was evaluated by wound scratch assay and Boyden chamber assay. RESULTS: Twist
      protein was highly expressed in gastric cancer samples. Twist gene silencing
      significantly induced apoptosis, cell cycle arrest at G0/G1 phase, proliferation
      inhibition, and reduced the ability of migration and invasion in human gastric
      cancer SGC7901 cells. Meanwhile, both caspase-3 and caspase-9 were activated.
      CONCLUSION: The Twist gene could serve as a potential molecular target for gene
      therapy of gastric cancer with targeted small interfering RNA.

PMID- 25780291
TI  - Heme oxygenase-1 protects rat liver against warm ischemia/reperfusion injury via
      TLR2/TLR4-triggered signaling pathways.
AB  - AIM: To investigate the efficacy and molecular mechanisms of induced heme
      oxygenase (HO)-1 in protecting liver from warm ischemia/reperfusion (I/R) injury.
      METHODS: Partial warm ischemia was produced in the left and middle hepatic lobes
      of SD rats for 75 min, followed by 6 h of reperfusion. Rats were treated with
      saline, cobalt protoporphyrin (CoPP) or zinc protoporphyrin (ZnPP) at 24 h prior
      to the ischemia insult. Blood and samples of ischemic lobes subjected to ischemia
      were collected at 6 h after reperfusion. Serum transaminases level, plasma
      lactate dehydrogenase and myeloperoxidase activity in liver were measured. Liver
      histological injury and inflammatory cell infiltration were evaluated by tissue
      section and liver immunohistochemical analysis. We used quantitative reverse
      transcription polymerase chain reaction to analyze liver expression of
      inflammatory cytokines and chemokines. The cell lysates were subjected to
      immunoprecipitation with anti-Toll-IL-1R-containing adaptor inducing interferon
      beta (TRIF) and anti-myeloid differentiation factor 88 (MyD88), and then the
      immunoprecipitates were analyzed by SDS-PAGE and immunoblotted with the indicated
      antibodies. RESULTS: HO-1 protected livers from I/R injury, as evidenced by
      diminished liver enzymes and well-preserved tissue architecture. In comparison
      with ZnPP livers 6 h after surgery, CoPP treatment livers showed a significant
      increase inflammatory cell infiltration of lymphocytes, plasma cells, neutrophils
      and macrophages. The Toll-like receptor (TLR)-4 and TANK binding kinase 1 protein
      levels of rats treated with CoPP significantly reduced in TRIF-immunoprecipitated
      complex, as compared with ZnPP treatment. In addition, pretreatment with CoPP
      reduced the expression levels of TLR2, TLR4, IL-1R-associated kinase (IRAK)-1 and
      tumor necrosis factor receptor-associated factor 6 in MyD88-immunoprecipitated
      complex. The inflammatory cytokines and chemokines mRNA expression rapidly
      decreased in CoPP-pretreated liver, compared with the ZnPP-treated group.
      However, the expression of negative regulators Toll-interacting protein,
      suppressor of cytokine signaling-1, IRAK-M and Src homology 2 domain-containing
      inositol-5-phosphatase-1 in CoPP treatment rats were markedly up-regulated as
      compared with ZnPP-treated rats. CONCLUSION: HO-1 protects liver against I/R
      injury by inhibiting TLR2/TLR4-triggered MyD88- and TRIF-dependent signaling
      pathways and increasing expression of negative regulators of TLR signaling in
      rats.

PMID- 25780292
TI  - Tumor suppressor role of miR-133a in gastric cancer by repressing IGF1R.
AB  - AIM: To investigate the function and mechanism of miR-133a in gastric cancer (GC)
      and its relationship with clinicopathological characteristics of GC. METHODS: A
      total of 105 GC patients who underwent surgical resection as primary treatment
      were selected for this study. Real-time quantitative reverse transcriptase
      polymerase chain (qRT-PCR) was used to examine the expression levels of miR-133a
      in human GC and adjacent non-tumor tissues, as well as in GC cell lines (SGC
      7901, BGC-823, MGC-803, and AGS) and a human gastric mucosal epithelial cell line
      (GES-1). The biological role of miRNA (miR)-133a was assessed in the GC cell
      lines using MTT, apoptosis, migration and invasion, and colony formation assays,
      and xenograft tumorigenesis. qRT-PCR and western blot analyses were used to
      evaluate the potential target gene expression of miR-133a. Pearson's correlation
      was calculated to evaluate the correlation between miR-133a and insulin-like
      growth factor 1 receptor (IGF1R) expression. The regulation of IGF1R by miR-133a
      was verified using the luciferase reporter assay. RESULTS: In 80% of the 105 GC
      patients, the mean expression of miR-133a was significantly downregulated in
      tumor tissues compared with adjacent normal tissues (1.215 +/- 0.1477 vs 3.093 +/
      0.4104, P < 0.0001). Downregulation of miR-133a was significantly correlated
      with the degree of differentiation (P = 0.01), local invasion (P = 0.001) and TNM
      stage (P = 0.02) in GC patients. Compared with a control construct, forced
      expression of miR-133a in GC cell lines inhibited proliferation (0.4787 +/-
      0.0219 vs 0.7050 +/- 0.0147, P = 0.0013 in SGC-7901 cells; and 0.5448 +/- 0.0085
      vs 0.7270 +/- 0.0084, P = 0.001 in MGC-803 cells); migration (0.6333 +/- 0.0233
      vs 1.037 +/- 0.0584, P = 0.003 in SGC-7901 cells; 0.6126 +/- 0.0311 vs 1.024 +/-
      0.0456, P = 0.0017 in MGC-803 cells); and invasion (0.613 +/- 0.0399 vs 1.033 +/-
      0.0278, P = 0.0013 in SGC-7901 cells; 0.7433 +/- 0.0221 vs 1.017 +/- 0.0311, P =
      0.002 in MGC-803 cells). It also induced apoptosis (18.19% +/- 0.2483% vs 5.887%
      +/- 0.3837%, P < 0.0001 in SGC-7901 cells; 22.69% +/- 0.7846% vs 9.347% +/-
      0.3012%, P < 0.0001 in MGC-803 cells). Furthermore, miR-133a inhibited tumor
      growth and xenograft tumorigenesis of SGC -7901 cells in vivo. In addition, we
      identified IGF1R as a regulatory target of miR-133a in GC. CONCLUSION: This study
      suggests that miR-133a is downregulated in GC and functions as a tumor suppressor
      in vitro and in vivo partly by repressing IGF1R.

PMID- 25780293
TI  - Increased VGLUT3 involved in visceral hyperalgesia in a rat model of irritable
      bowel syndrome.
AB  - AIM: To investigate the activity of vesicular glutamate transporter-3 (VGLUT3) in
      a visceral hyperalgesia rat model of irritable bowel syndrome, and the role of
      mast cells (MCs). METHODS: Transient intestinal infection was induced by oral
      administration of Trichinella spiralis larvae in rats. On the 100(th) day post
      infection (PI), the rats were divided into an acute cold restraint stress (ACRS)
      group and a non-stressed group. Age-matched untreated rats served as controls.
      The abdominal withdrawal reflex was used to measure the visceromotor response to
      colorectal distension (CRD). The expression levels of VGLUT3 in peripheral and
      central neurons were analyzed by immunofluorescence and western blotting.
      RESULTS: VGLUT3 expression in the L6S1 dorsal root ganglion cells was
      significantly higher in the PI group than in the control group (0.32 +/- 0.009 vs
      0.22 +/- 0.008, P < 0.01), and there was no significant difference in the
      expression of VGLUT3 between MC-deficient rats and their normal wild-type
      littermates. Immunofluorescence showed that the expression levels of VGLUT3 in PI
      + ACRS rats were enhanced in the prefrontal cortex of the brain compared with the
      control group. CONCLUSION: VGLUT3 is involved in the pathogenesis of visceral
      hyperalgesia. Coexpression of c-fos, 5-hydroxytryptamine and VGLUT3 after CRD was
      observed in associated neuronal pathways. Increased VGLUT3 induced by transient
      intestinal infection was found in peripheral nerves, and was independent of MCs.
      Moreover, the expression of VGLUT3 was enhanced in the prefrontal cortex in rats
      with induced infection and stress.

PMID- 25780294
TI  - Indeterminate pulmonary nodules in colorectal cancer.
AB  - AIM: To investigate the clinicopathologic parameters of pulmonary metastasis in
      colorectal cancer (CRC) patients after lung operation of indeterminate pulmonary
      nodules (IPNs). METHODS: From a prospective database of CRC patients, 40 cases
      that underwent lung operation between November 2008 and December 2012 for
      suspicious metastatic pulmonary nodules on chest computed tomography (CT) were
      enrolled. The decision to perform a lung operation was made if the patient met
      the following criteria: (1) completely resected or resectable primary CRC; (2)
      completely resectable IPNs; (3) controlled or controllable extrapulmonary
      metastasis; and (4) adequate general condition and pulmonary function to tolerate
      pulmonary operation. Lung operation was performed by a thoracic surgeon without
      CT-guided biopsy for pathologic confirmation. RESULTS: A total of 40 cases of
      lung resection was performed in 29 patients. Five patients underwent repeated
      lung resection. The final pathology result showed metastasis from the CRC in 30
      cases (75%) and benign pathology in 10 cases (25%). The primary tumor site was
      the rectum in 26/30 (86.6%) cases with pulmonary metastasis, but only 3/10 (30%)
      cases in the benign group had a primary rectal cancer (P = 0.001). Positron
      emission tomography (PET)-CT was performed for 22/30 (73.4%) patients in the lung
      metastasis group and for 6/10 (60.0%) patients in the benign group. PET-CT
      revealed hot uptake of (18)fluorine 2-fluoro-2-deoxy-D-glucose with all IPNs in
      both groups. The group with pulmonary metastasis had a higher incidence of
      primary rectal cancer (P = 0.001), a more advanced tumor stage (P = 0.011), and
      more frequent lymphatic invasion of tumor cells (P = 0.005). Six cases with
      previous liver metastasectomy were present in the lung metastasis group. Serum
      carcinoembryonic antigen levels before lung operation were not elevated in any of
      the patients. CONCLUSION: The stage and location of the primary tumor and tumor
      cell infiltration of lymphatics provide useful indicators for deciding on lung
      resection of IPNs in CRC.

PMID- 25780295
TI  - Intracorporeal esophagojejunostomy using the double stapling technique after
      laparoscopic total gastrectomy: A retrospective case-series study.
AB  - AIM: To introduce a simple and safe anvil insertion technique to esophagus during
      laparoscopic total gastrectomy (LTG). METHODS: Between July 2010 and December
      2012, 58 consecutive patients with early gastric cancer underwent LTG were
      enrolled. We performed a simple and safe Roux-en-Y esophagojejunostomy using the
      double stapling technique to all patients. Then patients' characteristics,
      perioperative outcome and histopathologic data were analyzed retrospectively.
      RESULTS: The mean age and body mass index were 59.3 +/- 9.7 years and 22.7 +/-
      2.6 kg/m(2). The mean operation, reconstruction and anvil insertion times (from
      gastric incision to linear stapling) were 251.8 +/- 57.0, 43.1 +/- 2.8 and 4.2 +/
      1.9 min, respectively. Intraoperative blood loss was 204.6 +/- 156.3 mL and
      there was no open conversion. The postoperative complications were in 8 cases
      (delayed gastric emptying in 4 cases, pulmonary complication in 2 cases,
      pancreatitis in 1 case, anastomotic stricture in 1 case). Anastomotic stricture
      occurred after discharge and was recovered by endoscopic intervention. The
      patients were discharged at a mean of 9.6 +/- 2.0 d after surgery. Neither
      leakage nor bleeding from the esophagojejunostomy occurred postoperatively. The
      mean proximal margin of specimen was 2.7 +/- 2.8 cm CONCLUSION: Roux-en Y
      esophagojejunostomy using the double stapling technique is simple and rapid, and
      it may offer a solid, alternative reconstruction method for LTG or proximal
      gastrectomy.

PMID- 25780296
TI  - Endoscopic resection using band ligation for esophageal SMT in less than 10 mm.
AB  - AIM: To evaluate the safety and feasibility of endoscopic resection using band
      ligation (EMR-B) for the diagnostic and therapeutic removal of tumors located in
      the esophageal subepithelial region having originated from the submucosa.
      METHODS: From May 2009 to September 2014, after medical chart and endoscopic
      ultrasonography report review, a total of 15 esophageal tumors located in the
      submucosal layer were resected by EMR-B. Previous symptom, location, pathology,
      complete resection rate, incidence of complications, incidence of minor
      complication, size, length of procedures time and follow up months were
      evaluated. To evaluate local recurrence at the resection site, periodic follow-up
      endoscopic examination was undertaken in all of the patients. The first
      endoscopic examination was performed about 6 mo after the endoscopic resection.
      Thereafter, the endoscopic follow up were scheduled annually. RESULTS: The mean
      age was 50.3 +/- 9.67 years. The mean tumor size was 6.93 +/- 3.15 mm and most of
      the lesions size was between 5-10 mm in diameter (10/15, 66.6%). In all patients,
      endoscopic en bloc resection was achieved. In one patient, the vertical margin
      was involved. The mean procedural time was 8.86 +/- 3.66 min. In all patients, no
      evidence of severe complications such as perforation or bleeding occurred. Minor
      complications such as chest pain (2/15, 13.3%) and heartburn (3/15, 13.3%) were
      reported but they symptoms were controlled by proton pump inhibitors, ulcermin
      and/or analgesics. Histologic assessments of the removed specimens revealed 10
      granular cell tumors (66.6%), 4 leiomyomas (16.6%) and one lipoma (6.6%). No
      recurrence was observed during the mean follow up period of 45 +/- 3.5 mo (range:
      5-64 mo). CONCLUSION: EMR-B might be considered safe and effective for the
      diagnosis and treatment of lesions measuring less than 10 mm in diameter.

PMID- 25780297
TI  - Cross-modality PET/CT and contrast-enhanced CT imaging for pancreatic cancer.
AB  - AIM: To explore the diagnostic value of the cross-modality fusion images provided
      by positron emission tomography/computed tomography (PET/CT) and contrast
      enhanced CT (CECT) for pancreatic cancer (PC). METHODS: Data from 70 patients
      with pancreatic lesions who underwent CECT and PET/CT examinations at our
      hospital from August 2010 to October 2012 were analyzed. PET/CECT for the cross
      modality image fusion was obtained using TureD software. The diagnostic
      efficiencies of PET/CT, CECT and PET/CECT were calculated and compared with each
      other using a chi(2) test. P < 0.05 was considered to indicate statistical
      significance. RESULTS: Of the total 70 patients, 50 had PC and 20 had benign
      lesions. The differences in the sensitivity, negative predictive value (NPV), and
      accuracy between CECT and PET/CECT in detecting PC were statistically significant
      (P < 0.05 for each). In 15 of the 31 patients with PC who underwent a surgical
      operation, peripancreatic vessel invasion was verified. The differences in the
      sensitivity, positive predictive value, NPV, and accuracy of CECT vs PET/CT and
      PET/CECT vs PET/CT in diagnosing peripancreatic vessel invasion were
      statistically significant (P < 0.05 for each). In 19 of the 31 patients with PC
      who underwent a surgical operation, regional lymph node metastasis was verified
      by postsurgical histology. There was no statistically significant difference
      among the three methods in detecting regional lymph node metastasis (P > 0.05 for
      each). In 17 of the 50 patients with PC confirmed by histology or clinical follow
      up, distant metastasis was confirmed. The differences in the sensitivity and NPV
      between CECT and PET/CECT in detecting distant metastasis were statistically
      significant (P < 0.05 for each). CONCLUSION: Cross-modality image fusion of
      PET/CT and CECT is a convenient and effective method that can be used to diagnose
      and stage PC, compensating for the defects of PET/CT and CECT when they are
      conducted individually.

PMID- 25780298
TI  - Clinical outcome of medium-sized hepatocellular carcinoma treated with microwave
      ablation.
AB  - AIM: To evaluate the outcomes of patients with medium-sized hepatocellular
      carcinoma (HCC) who underwent percutaneous microwave ablation (MWA). METHODS: We
      retrospectively reviewed all patients with a single medium-sized HCC who
      underwent percutaneous MWA from January 2010 to January 2013. Technical success,
      technical effectiveness and complications were subsequently observed. Survival
      curves were constructed using the Kaplan-Meier method. The Cox proportional
      hazards model was fitted to each variable. The relative prognostic significance
      of the variables for predicting overall survival rate, recurrence-free survival
      rate and local tumor recurrence(s) was assessed using univariate analysis. All
      variables with a P value < 0.20 were subjected to multivariate analysis. RESULTS:
      The study included 182 patients (mean age, 58 years; age range: 22-86 years) with
      a single HCC (mean size, 3.72 +/- 0.54 cm; range: 3.02-5.00 cm). The estimated
      technical effectiveness rate was 93% in 182 patients. The major complication rate
      was 2.7% (5/182), including liver abscess in 4 cases, and abdominal bleeding at
      the puncture site in 1 case. Thirty-day mortality rate was 0.5% (1/182). One
      patient died due to liver abscess-related septicemia. Cumulative recurrence-free
      survival and overall survival (OS) rates were 51%, 36%, 27% and 89%, 74%, 60% at
      1, 2, and 3 years, respectively. Age (P = 0.017) and tumor diameter (P = 0.029)
      were independent factors associated with local tumor recurrence. None of the
      factors had a statistically significant impact on recurrence-free survival. Serum
      albumin level (P = 0.009) and new lesion(s) (P = 0.029) were independently
      associated with OS. CONCLUSION: Percutaneous MWA is a relatively safe and
      effective treatment for patients with medium-sized HCC.

PMID- 25780299
TI  - Corticosteroid therapy in ulcerative colitis: Clinical response and predictors.
AB  - AIM: To evaluate clinical response to initial corticosteroid (CS) treatment in
      Chinese ulcerative colitis patients (UC) and identify predictors of clinical
      response. METHODS: Four hundred and twenty-three UC patients who were initially
      treated with oral or intravenous CS from 2007 to 2011 were retrospectively
      reviewed at eight inflammatory bowel disease centers in China, and 101
      consecutive cases with one-year follow-up were analyzed further for clinical
      response and predictors. Short-term outcomes within one month were classified as
      primary response and primary non-response. Long-term outcomes within one year
      were classified as prolonged CS response, CS dependence and secondary non
      response. CS refractoriness included primary and secondary non-response.
      Multivariate analyses were performed to identify predictors associated with
      clinical response. RESULTS: Within one month, 95.0% and 5.0% of the cases were
      classified into primary response and non-response, respectively. Within one year,
      41.6% of cases were assessed as prolonged CS response, while 49.5% as CS
      dependence and 4.0% as secondary non-response. The rate of CS refractoriness was
      8.9%, while the cumulative rate of surgery was 6.9% within one year. After
      multivariate analysis of all the variables, tenesmus was found to be a negative
      predictor of CS dependence (OR = 0.336; 95%CI: 0.147-0.768; P = 0.013) and weight
      loss as a predictor of CS refractoriness (OR = 5.662; 95%CI: 1.111-28.857; P =
      0.040). After one-month treatment, sustained high Sutherland score (>= 6) also
      predicted CS dependence (OR = 2.347; 95%CI: 0.935-5.890; P = 0.014). CONCLUSION:
      Tenesmus was a negative predictor of CS dependence, while weight loss and
      sustained high Sutherland score were strongly associated with poor CS response.

PMID- 25780300
TI  - Evaluation of the prognostic value of liver stiffness in patients with hepatitis
      C virus treated with triple or dual antiviral therapy: A prospective pilot study.
AB  - AIM: To evaluate the association between liver stiffness (LS) prior to the
      initiation of dual/triple therapy and viral response. METHODS: LS was measured in
      all patients before treatment was administered. The therapeutic approach was
      based on hepatic, virological, and immunological evaluations and considered the
      fact that patients with severe fibrosis (F3) or compensated cirrhosis (F4) in
      Child-Pugh class A are the primary candidates for triple therapy. In total, 65
      hepatitis C virus (HCV) patients were treated with Peg-interferon/ribavirin (Peg
      IFN/RBV); 24 patients were classified as genotypes 1/4 (36.92%), and 41 patients
      were classified as genotypes 2/3 (63.08%) (dual therapy). In addition, 20 HCV
      treatment-experienced genotype 1 patients were treated with PegIFN-RBV and
      boceprevir (triple therapy). Wilcoxon rank-sum tests were used to compare the
      groups. RESULTS: LS significantly differed between dual therapy and triple
      therapy (P = 0.002). The mean LS value before dual therapy treatment was 8.61 +/-
      5.79 kPa and was significantly different between patients achieving a sustained
      virologic response (SVR) 24 weeks after therapy and those who did not (7.23 +/-
      5.18 kPa vs 11.72 +/- 5.99 kPa, respectively, P = 0.0003). The relative risk of
      non-response to therapy was 4.45 (95%CI: 2.32-8.55). The attributable risk of non
      response to therapy was 49%. The mean LS value before triple therapy treatment
      was 13.29 +/- 8.57 kPa and was significantly different between patients achieving
      and not achieving SVR24 (9.41 +/- 5.05 vs 19.11 +/- 9.74, respectively; P =
      0.008). The relative risk of non-response to therapy was 5.57% (95%CI: 1.50
      20.65). The attributable risk of non-response to therapy (70%) was increased
      compared with dual therapy patients. Pre-treatment stiffness > 12 kPa was
      significantly associated with non-SVR (P < 0.025) in both groups. CONCLUSION: Pre
      treatment liver stiffness may be useful for predicting the response to treatment
      in patients treated with either dual or triple anti-HCV therapy.

PMID- 25780301
TI  - Adipokines levels are associated with the severity of liver disease in patients
      with alcoholic cirrhosis.
AB  - AIM: To investigate the adipokine levels of leptin, adiponectin, resistin,
      visfatin, retinol-binding protein 4 (RBP4), apelin in alcoholic liver cirrhosis
      (ALC). METHODS: Forty non-diabetic ALC patients [median age: 59 years, males: 35
      (87.5%), Child-Pugh (CP) score: median 7 (5-12), CP A/B/C: 18/10/12, Model for
      End-stage Liver Disease (MELD): median 10 (6-25), follow-up: median 32.5 mo (10
      43)] were prospectively included. The serum adipokine levels were estimated in
      duplicate by ELISA. Somatometric characteristics were assessed with tetrapolar
      bioelectrical impedance analysis. Pearson's rank correlation coefficient was used
      to assess possible associations with adipokine levels. Univariate and
      multivariate Cox regression analysis was used to determine independent predictors
      for overall survival. RESULTS: Body mass index: median 25.9 (range: 20.1-39.3),
      fat: 23.4% (7.6-42.1), fat mass: 17.8 (5.49-45.4), free fat mass: 56.1 (39.6
      74.4), total body water (TBW): 40.6 (29.8-58.8). Leptin and visfatin levels were
      positively associated with fat mass (P < 0.001/P = 0.027, respectively) and RBP4
      with TBW (P = 0.025). Median adiponectin levels were significantly higher in CPC
      compared to CPA (CPA: 7.99 +/- 14.07, CPB: 7.66 +/- 3.48, CPC: 25.73 +/- 26.8, P
      = 0.04), whereas median RBP4 and apelin levels decreased across the spectrum of
      disease severity (P = 0.006/P = 0.034, respectively). Following adjustment for
      fat mass, visfatin and adiponectin levels were significantly increased from CPA
      to CPC (both P < 0.001), whereas an inverse correlation was observed for both
      RBP4 and apelin (both P < 0.001). In the multivariate Cox regression analysis,
      only MELD had an independent association with overall survival (HR = 1.53, 95%CI:
      1.05-2.32; P = 0.029). CONCLUSION: Adipokines are associated with deteriorating
      liver function in a complex manner in patients with alcoholic liver cirrhosis.

PMID- 25780302
TI  - Gastroesophageal reflux in asymptomatic obese subjects: An esophageal impedance
      pH study.
AB  - AIM: To investigate the relationship between reflux and body mass index (BMI) in
      the asymptomatic obese population using the impedance-pH technique. METHODS:
      Gastroesophageal reflux is frequent in the obese population. However, the
      relationship between acid reflux and BMI in asymptomatic obese people is unclear.
      Forty-six obese (BMI > 25 kg/m(2)) people were enrolled in this prospective
      study. We evaluated the demographic findings and 24-h impedance pH values of the
      whole group. Gas, acid (pH < 4), weak acid (pH = 4-7) and weak alkaline (pH >= 7)
      reflux parameters were analyzed. RESULTS: The mean age of patients was 49.47 +/-
      12.24 years, and half of them were men. The mean BMI was 30.64 +/- 3.95 kg/m(2)
      (25.14-45.58 kg/m(2)). BMI of 23 was over 30 kg/m(2). Seventeen patients had a
      comorbidity (hypertension, diabetes mellitus, or ischemic heart disease).
      Endoscopic examination revealed esophagitis in 13 of the 28 subjects (10 Grade A,
      3 Grade B). The subjects were divided into two groups according to BMI (< 30 and
      > 30 kg/m(2)). Demographic and endoscopic findings, and impedance results were
      similar in these two groups. However, there was a positive correlation between
      BMI and total and supine pH < 4 episodes (P = 0.002, r = 0.414; P = 0.000, r =
      0.542), pH < 4 reflux time (P = 0.015, r = 0.319; P = 0.003, r = 0.403), and
      DeMeester score (P = 0.012, r = 0.333). CONCLUSION: Acid reflux is correlated
      with BMI in asymptomatic obese individuals.

PMID- 25780303
TI  - C-arm Lipiodol CT in transcatheter arterial chemoembolization for small
      hepatocellular carcinoma.
AB  - AIM: To investigate the value of C-arm Lipiodol computed tomography (CT) for
      intra-procedural hepatocellular carcinoma (HCC) lesion detection during
      transcatheter arterial chemoembolization (TACE). METHODS: Forty patients (37
      male, 3 female; mean age, 52.6 +/- 12.5 years, age range: 25-82 years) diagnosed
      with HCC were enrolled in this study. All patients underwent 64-slice CT 1-2 wk
      before TACE. During the procedure, hepatic angiography was performed first.
      Following diagnostic embolization with Lipiodol injected into the hepatic artery,
      a C-arm CT scan was immediately conducted (C-arm Lipiodol CT). If new HCC lesions
      were confirmed, gelfoam particles were super-selectively injected into the tumor
      nourishing blood vessel. A Lipiodol CT scan was performed 7-14 d after TACE. All
      images acquired from 64-slice CT, digital subtraction angiography (DSA), C-arm
      Lipiodol CT and Lipiodol CT were retrospectively reviewed by four radiologists
      and the number of detected lesions in each examination was counted, respectively.
      The results of Lipiodol CT were taken as the diagnostic reference. Alpha
      fetoprotein values were examined both before and after TACE. This study only
      takes into account the lesions that were not found or were considered suspicious
      on 64-slice CT before TACE. RESULTS: Preprocedural 64-slice CT detected a total
      of 13 suspicious lesions in the 40 patients. DSA detected ten definite and four
      suspicious lesions. C-arm Lipiodol CT detected 71 lesions in total and Lipiodol
      CT confirmed 67 lesions with a diameter range of 3-12 mm. Four false-positive
      lesions, which were detected by C-arm Lipiodol CT, were considered to be hepatic
      artery-portal vein fistulas. The average alpha-fetoprotein values before and
      after TACE were significantly different (452.3 +/- 192.6 ng/mL vs 223.8 +/- 93.2
      ng/mL; P = 0.039). CONCLUSION: C-arm Lipiodol CT has a higher diagnostic
      sensitivity for small HCC lesions. This technique may help physicians make
      intraprocedural decisions to provide patients with earlier treatment.

PMID- 25780304
TI  - Electrolyte changes after bowel preparation for colonoscopy: A randomized
      controlled multicenter trial.
AB  - AIM: To investigate the electrolyte changes between 2-L polyethylene glycol with
      ascorbic acid 20 g (PEG-Asc) and 4-L PEG solutions. METHODS: From August 2012 to
      February 2013, a total of 226 patients were enrolled at four tertiary hospitals.
      All patients were randomly allocated to a PEG-Asc group or a 4-L PEG. Before
      colonoscopy, patients completed a questionnaire to assess bowel preparation
      related symptoms, satisfaction, and willingness. Endoscopists assessed the bowel
      preparation using the Boston Bowel Preparation Scale (BBPS). In addition, blood
      tests, including serum electrolytes, serum osmolarity, and urine osmolarity were
      evaluated both before and after the procedure. RESULTS: A total of 226 patients
      were analyzed. BBPS scores were similar and the adequate bowel preparation rate
      (BBPS >= 6) was not different between the two groups (PEG-Asc vs 4-L PEG, 73.2%
      vs 76.3%, P = 0.760). Bowel preparation-related symptoms also were not different
      between the two groups. The taste of PEG-Asc was better (41.1% vs 16.7%, P <
      0.001), and the willingness to undergo repeated bowel preparation was higher in
      the PEG-Asc group (73.2% vs 59.3%, P = 0.027) than in 4-L PEG. There were no
      significant changes in serum electrolytes in either group. CONCLUSION: In this
      multicenter trial, bowel preparation with PEG-Asc was better than 4-L PEG in
      terms of patient satisfaction, with similar degrees of bowel preparation and
      electrolyte changes.

PMID- 25780305
TI  - Prognostic value of (18)F-FDG PET/CT in liver transplantation for
      hepatocarcinoma.
AB  - AIM: To evaluate the prognostic value of pretreatment FDG positron emission
      tomography computed tomography (PET-CT) in patients with hepatocarcinoma treated
      by liver transplantation (LT). METHODS: The authors retrospectively analyzed the
      data of 27 patients (mean age 58 +/- 9 years) who underwent FDG PET-CT before LT
      for hepatocarcinoma. Mean follow-up was 26 +/- 18 mo. The FDG PET/CT was
      performed according to a standard clinical protocol: 4 MBqFDG/kg body weight,
      uptake 60 min, low-dose non-enhanced CT. The authors measured the SUVmax and
      SUVmean of the tumor and the normal liver. The tumor/liver activity ratios
      (RSUVmax and RSUVmean) were tested as prognostic factors and compared to the
      following conventional prognostic factors: MILAN, CLIP, OKUDA, TNM stage,
      alphafoetoprotein level, portal thrombosis, size of the largest nodule, tumor
      differentiation, microvascular invasion, underlying cirrhosis and liver function.
      RESULTS: Overall and recurrence free survivals were 80.7% and 67.4% at 3 years,
      and 70.6% and 67.4% at 5 years, respectively. According to a multivariate Cox
      model, only FDG PET/CT RSUVmax predicted recurrence free survival. Even though
      the MILAN criteria alone were not predictive, it is worth noting that none of the
      patients outside the MILAN criteria and with RSUVmax < 1.15 relapsed. CONCLUSION:
      FDG PET/CT with an RSUVmax cut-off value of 1.15 is a strong prognostic factor
      for recurrence and death in patients with HCC treated by LT in this retrospective
      series. Further prospective studies should test whether this metabolic index
      should be systematically included in the preoperative assessment.

PMID- 25780306
TI  - Decaprenyl diphosphate synthase subunit 2 as a prognosis factor in hepatocellular
      carcinoma.
AB  - AIM: To investigate the involvement of decaprenyl diphosphate synthase subunit 2
      (PDSS2) in development and progression of human hepatocellular carcinoma (HCC).
      METHODS: PDSS2 protein expression was examined in well- and poorly differentiated
      HCC tumor samples. The levels of PDSS2 expression were compared with clinical
      features and prognosis of HCC patients. The effects of PDSS2 on cell
      proliferation, cell cycle, apoptosis, cell migration, and invasion in HCC HepG2
      cells were also investigated. RESULTS: PDSS2 was downregulated in poorly
      differentiated cancer samples compared with well-differentiated tumor samples,
      and the expression level was markedly lower in HCC tissues than in histologically
      normal tissue adjacent to the cancer. Reduced protein expression was negatively
      associated with the status of HCC progression. In addition, overexpression of
      PDSS2 dramatically suppressed cell proliferation and colony formation, and
      induced apoptosis in HepG2 cells by inducing G1-phase cell-cycle arrest. The
      migration and invasion capabilities of HepG2 cells were significantly decreased
      following PDSS2 overexpression. CONCLUSION: Decreased PDSS2 expression is an
      unfavorable prognostic factor for HCC, and PDSS2 has potent anticancer activity
      in HCC tissues and HepG2 cells.

PMID- 25780307
TI  - Cutaneous metastasis of cholangiocarcinoma.
AB  - AIM: To investigate the clinical characteristics and prognostic factors of
      cutaneous metastasis of cholangiocarcinoma by a retrospective analysis of
      published cases. METHODS: An extensive search was conducted in the English
      literature within the PubMed database using the following keywords: cutaneous
      metastasis or skin metastasis and cholangiocarcinoma or bile duct. The data of 30
      patients from 21 articles from 1978 to 2014 were analyzed. Patient data retrieved
      from the articles included the following: age, gender, time cutaneous metastasis
      occurred, number of cutaneous metastases throughout life, sites of initial
      cutaneous metastasis, anatomic site, pathology and differentiation of
      cholangiocarcinoma, and immunohistochemical results of the cutaneous metastasis.
      The assessment of overall survival after cutaneous metastasis (OSCM) was the
      primary endpoint. RESULTS: The median age at diagnosis of cutaneous metastasis of
      cholangiocarcinoma was 60.0 years (range: 35-77). This metastasis showed a
      predilection towards males, with a male to female ratio of 3.29. In 8 cases
      (27.6%), skin metastasis was the first sign of cholangiocarcinoma. Additionally,
      18 cases (60.0%) manifested single cutaneous metastasis, while 12 cases (40.0%)
      demonstrated multiple skin metastases. In 50.0% of patients, the metastasis
      occurred in the drainage region, while 50.0% of patients had distant cutaneous
      metastases. The scalp was the most frequently involved region of distant skin
      metastasis, occurring in 36.7% of patients. The median OSCM of cholangiocarcinoma
      was 4.0 mo. Patient age and cutaneous metastatic sites showed no significant
      relation with OSCM, while male gender and single metastasis of the skin were
      associated with a poorer OSCM (hazard ratio: 0.168; P = 0.005, and hazard ratio:
      0.296; P = 0.011, respectively). CONCLUSION: The prognosis of cutaneous
      metastasis of cholangiocarcinoma is dismal. Both male gender and single skin
      metastasis are associated with a poorer OSCM.

PMID- 25780308
TI  - Effectiveness of probiotics in irritable bowel syndrome: Updated systematic
      review with meta-analysis.
AB  - AIM: To investigate the efficacy of probiotics in irritable bowel syndrome (IBS)
      patients. METHODS: PubMed, Cochrane library, Scopus, Google Scholar, and
      Clinicaltrial.gov databases were searched for literature published between
      September 2007 and December 2013. The applied Mesh terms were "probiotics,"
      "irritable bowel syndrome," and "irritable bowel syndrome treatment." The
      collected data contained24 clinical trials, of which 15 were eligible for meta
      analysis and nine were reviewed systematically. All studies were randomized
      placebo-controlled trials in patients with IBS that investigated the efficacy of
      probiotics in IBS improvement. The Jadad score was used to assess the
      methodological quality of trials. The quality scale ranges from 0 to 5 points,
      with a score <= 2 indicating a low quality report, and a score of >= 3 indicating
      a high quality report. Relative risk (RR), standardized effect size, and 95%CI
      were calculated using the DerSimonian-Laird method. The Cochran Q test was used
      to test heterogeneity with P < 0.05. Funnel plots were constructed and Egger's
      and Begg-Mazumdar tests were performed to assess publication bias. RESULTS: A
      total of 1793 patients were included in the meta-analysis. The RR of responders
      to therapies based on abdominal pain score in IBS patients for two included
      trials comparing probiotics to placebo was 1.96 (95%CI: 1.14-3.36; P = 0.01). RR
      of responders to therapies based on a global symptom score in IBS patients for
      two included trials comparing probiotics with placebo was 2.43 (95%CI: 1.13-5.21;
      P = 0.02). For adequate improvement of general symptoms in IBS patients, the RR
      of seven included trials (six studies) comparing probiotics with placebo was 2.14
      (95%CI: 1.08-4.26; P = 0.03). Distension, bloating, and flatulence were evaluated
      using an IBS severity scoring system in three trials (two studies) to compare the
      effect of probiotic therapy in IBS patients with placebo, the standardized effect
      size of mean differences for probiotics therapy was -2.57 (95%CI: -13.05--7.92).
      CONCLUSION: Probiotics reduce pain and symptom severity scores. The results
      demonstrate the beneficial effects of probiotics in IBS patients in comparison
      with placebo.

PMID- 25780309
TI  - Association between diabetes mellitus and gastroesophageal reflux disease: A meta
      analysis.
AB  - AIM: To investigate whether there is a link between diabetes mellitus (DM) and
      gastroesophageal reflux disease (GERD). METHODS: We conducted a systematic search
      of PubMed and Web of Science databases, from their respective inceptions until
      December 31, 2013, for articles evaluating the relationship between DM and GERD.
      Studies were selected for analysis based on certain inclusion and exclusion
      criteria. Data were extracted from each study on the basis of predefined items. A
      meta-analysis was performed to compare the odds ratio (OR) in DM between
      individuals with and without GERD using a fixed effect or random effect model,
      depending on the absence or presence of significant heterogeneity. Subgroup
      analyses were used to identify sources of heterogeneity. Publication bias was
      assessed by Begg's test. To evaluate the results, we also performed a sensitivity
      analysis. RESULTS: When the electronic database and hand searches were combined,
      a total of nine eligible articles involving 9067 cases and 81 968 controls were
      included in our meta-analysis. Based on the random-effects model, these studies
      identified a significant association between DM and the risk of GERD (overall OR
      = 1.61; 95%CI: 1.36-1.91; P = 0.003). Subgroup analyses indicated that this
      result persisted in studies on populations from Eastern countries (OR = 1.71;
      95%CI: 1.38-2.12; P = 0.003) and in younger patients (mean age < 50 years) (OR =
      1.70; 95%CI: 1.22-2.37; P = 0.001). No significant publication bias was observed
      in this meta-analysis using Begg(')s test (P = 0.175). The sensitivity analysis
      also confirmed the stability of our results. CONCLUSION: This meta-analysis
      suggests that patients with DM are at greater risk of GERD than those who do not
      have DM.

PMID- 25780310
TI  - Outcomes for jejunal interposition reconstruction compared with Roux-en-Y
      anastomosis: A meta-analysis.
AB  - AIM: To compare the clinical outcomes between jejunal interposition
      reconstruction and Roux-en-Y anastomosis after total gastrostomy in patients with
      gastric cancer. METHODS: A systematic literature search was conducted by two
      independent researchers on PubMed, EMBASE, the Cochrane Library, Google Scholar,
      and other English literature databases, as well as the Chinese Academic Journal,
      Chinese Biomedical Literature Database, and other Chinese literature databases
      using "Gastrostomy", "Roux-en-Y", and "Interposition" as keywords. Data
      extraction and verification were performed on the literature included in this
      study. RevMan 5.2 software was used for data processing. A fixed-effects model
      was applied in the absence of heterogeneity between studies. A random effects
      model was applied in the presence of heterogeneity between studies. RESULTS: Ten
      studies with a total of 762 gastric cancer patients who underwent total
      gastrostomy were included in this study. Among them, 357 received jejunal
      interposition reconstruction after total gastrostomy, and 405 received Roux-en-Y
      anastomosis. Compared with Roux-en-Y anastomosis, jejunal interposition
      reconstruction significantly decreased the incidence of dumping syndrome (OR =
      0.18, 95%CI: 0.10-0.31; P < 0.001), increased the prognostic nutritional index
      [weighted mean difference (WMD) = 6.02, 95%CI: 1.82-10.22; P < 0.001], and
      improved the degree of postoperative weight loss [WMD = 2.47, 95%CI: -3.19-(
      1.75); P < 0.001]. However, there is no statistically significant difference in
      operative time, hospital stay, or incidence of reflux esophagitis. CONCLUSION:
      Compared with Roux-en-Y anastomosis, patients who underwent jejunal interposition
      reconstruction after total gastrostomy had a lower risk of postoperative long
      term complications and improved life quality.

PMID- 25780311
TI  - Nonselective beta-blockers in cirrhotic patients with no or small varices: A meta
      analysis.
AB  - AIM: To explore effects of nonselective beta-blockers (NSBBs) in cirrhotic
      patients with no or small varices. METHODS: The PubMed, EMBASE, Science Direct,
      and Cochrane library databases were searched for relevant papers. A meta-analysis
      was performed using ORs with 95%CI as the effect sizes. Subgroup analysis was
      conducted according to the studies including patients without varices and those
      with small varices. RESULTS: Overall, 784 papers were initially retrieved from
      the database searches, of which six randomized controlled trials were included in
      the meta-analysis. The incidences of large varices development (OR = 1.05, 95%CI:
      0.25-4.36; P = 0.95), first upper gastrointestinal bleeding (OR = 0.59, 95%CI:
      0.24-1.47; P = 0.26), and death (OR = 0.70, 95%CI: 0.45-1.10; P = 0.12) were
      similar between NSBB and placebo groups. However, the incidence of adverse events
      was significantly higher in the NSBB group compared with the placebo group (OR =
      3.47, 95%CI: 1.45-8.33; P = 0.005). The results of subgroup analyses were similar
      to those of overall analyses. CONCLUSION: The results of this meta-analysis
      indicate that NSBBs should not be recommended for cirrhotic patients with no or
      small varices.

PMID- 25780312
TI  - Successful surgical management of ruptured umbilical hernias in cirrhotic
      patients.
AB  - Acute umbilical hernia rupture in patients with hepatic cirrhosis and ascites is
      an unusual, but potentially life-threatening complication, with postoperative
      morbidity about 70% and mortality between 60%-80% after supportive care and 6%
      20% after urgent surgical repair. Management options include primary surgical
      repair with or without concomitant portal venous system decompression for the
      control of the ascites. We present a retrospective analysis of our centre's
      experience over the last 6 years. Our cohort consisted of 11 consecutive patients
      (median age: 53 years, range: 36-63 years) with advanced hepatic cirrhosis and
      refractory ascites. Appropriate patient resuscitation and optimisation with
      intravenous fluids, prophylactic antibiotics and local measures was instituted.
      One failed attempt for conservative management was followed by a successful
      primary repair. In all cases, with one exception, a primary repair with non
      absorbable Nylon, interrupted sutures, without mesh, was performed. The
      perioperative complication rate was 25% and the recurrence rate 8.3%. No
      mortality was recorded. Median length of hospital stay was 14 d (range: 4-31 d).
      Based on our experience, the management of ruptured umbilical hernias in patients
      with advanced hepatic cirrhosis and refractory ascites is feasible without the
      use of transjugular intrahepatic portosystemic shunt routinely in the
      preoperative period, provided that meticulous patient optimisation is performed. 

PMID- 25780313
TI  - Recurrent intussusception as initial manifestation of primary intestinal
      melanoma: Case report and literature review.
AB  - Enteric intussusception caused by primary intestinal malignant melanoma is a very
      rare cause of intestinal obstruction. We herein present a case of a 42-year-old
      female patient with no prior medical history of malignant melanoma, who was
      admitted with persistent abdominal pain, nausea, and vomiting. A computed
      tomography scan revealed an intestinal obstruction due to ileocolic
      intussusception. An emergency laparoscopy and subsequent laparotomy revealed
      multiple small solid tumors across the whole small bowel. An oncologic resection
      was not feasible due to the insufficient length of the remaining small bowel.
      Only a small segment of ileum, which included the largest tumors causing the
      intussusception, was resected. The pathologic examination revealed two intestinal
      malignant melanoma lesions. A systematic clinical examination, endoscopic
      procedures, and fluorodeoxyglucose positron emission tomography-computed
      tomography scan all failed to reveal any indication of cutaneous, anal, or
      retinal melanoma. Hence, the tumor was classified as a primary intestinal
      malignant melanoma with multiple intestinal metastases. Since a complete
      oncologic resection of tumors was not possible, in order to prevent future
      intestinal obstruction, a surgical resection of the largest lesions was performed
      with palliative intention. The epidemiology, clinical manifestations, diagnosis
      and management of primary intestinal malignant melanoma, and intestinal
      intussusception in adults are discussed along with a review of the current
      literature. 

PMID- 25780314
TI  - Esophageal diverticulum exposed during endoscopic submucosal dissection of
      superficial cancer.
AB  - Endoscopic submucosal dissection (ESD) is now widely accepted as a strategy to
      treat superficial esophageal neoplasms. The rate of adverse events, such as
      perforation, has been decreasing with the improvement of devices and techniques.
      In this paper, we report a case of esophageal cancer that had a diverticulum
      under cancerous epithelium. The diverticulum was not detected during preoperative
      examination, and led to perforation during the ESD procedure. Our case shows
      that, although rare, some diverticula can exist underneath the mucosal surface
      without obvious depression. If there is any sign of hidden diverticula during
      ESD, surgeons should proceed with caution or, depending on the case, the
      procedure should be discontinued to avoid adverse events. 

PMID- 25780315
TI  - Endoscopic submucosal dissection of a large colonic lipoma: Report of two cases.
AB  - A colonic lipoma is a very rare benign tumor that is usually asymptomatic and is
      found incidentally by colonoscopy. Patients with a large colonic lipoma may
      present with symptoms such as abdominal pain, bleeding, and colonic obstruction
      or intussusceptions. We report two patients with large colonic lipomas and
      symptoms. Standard endoscopic submucosal dissection (ESD) was performed to remove
      the lipomas instead of conventional surgical bowel resection. No complications
      were observed during or after the procedure. The tumors were resected en bloc,
      and the patients were discharged 2 d after ESD with a regular diet. The results
      indicate that ESD can be applied as safe and effective treatment for a large
      colonic lipoma. 

PMID- 25780316
TI  - Primary hepatic neuroendocrine tumor with multiple liver metastases: A case
      report with review of the literature.
AB  - We herein present a case involving a 41-year-old woman in whom ultrasound
      examination revealed multiple liver hemangiomas more than 3 years ago. Follow-up
      ultrasound examination revealed that the masses had significantly increased; the
      largest was located in the right lobe (about 8.2 cm * 7.4 cm * 6.0 cm). Abdominal
      multidetector computed tomography revealed multiple well-circumscribed,
      heterogeneous, hypodense masses (largest, 6.4 cm * 6.3 cm * 5.0 cm) with
      significant contrast enhancement during the arterial and portal phases and with
      contrast wash-out and peripheral enhancement during the delayed phases. Magnetic
      resonance images demonstrated multiple well-circumscribed, heterogeneous,
      hypointense hepatic masses with significant contrast enhancement (largest, 6.4 cm
      * 6.5 cm * 5.1 cm); multiple enlarged porta lymph nodes; and multiple slightly
      enlarged retroperitoneal lymph nodes. Histological and immunohistochemical
      examination of the right mass biopsy specimen suggested a malignant neoplasm that
      had originated from a neuroendocrine cell type (grade 2 well-differentiated
      neuroendocrine carcinoma). After performing a systemic examination to exclude
      metastasis from an extrahepatic primary site, we considered that the masses had
      arisen from a primary hepatic neuroendocrine tumor with multiple liver
      metastases. The patient underwent transcatheter arterial chemoembolization using
      a combination of oxaliplatin (150 mg) mixed with one bottle of gelatin sponge
      particles (560-710 MUm) and lipiodol (6 mL). Primary neuroendocrine tumors of the
      liver are extremely rare. This case is interesting because of the rarity of this
      neoplasm and previous misdiagnosis as multiple liver hemangiomas. Previously
      reported cases in the literature are also reviewed. 

PMID- 25780317
TI  - Eosinophilic gastroenteritis associated with eosinophilic cystitis: Computed
      tomography and magnetic resonance imaging findings.
AB  - Eosinophilic gastroenteritis (EG) is a rare, distinct clinical entity, and EG
      associated with eosinophilic cystitis (EC) is extremely rare and has not been
      well documented. Here, we report two cases of EG and coexistent EC along with
      findings from computed tomography (CT) and magnetic resonance imaging (MRI). An
      18-year-old male with a history of hematuria, urgency and occasional urodynia for
      two weeks and a 34-year-old male with a history of abdominal distention for one
      week were admitted to our hospital. Abdominal contrast-enhanced CT in both
      patients revealed wall thickening in different parts of the gastrointestinal
      tract with inhomogeneous reinforcement, coexistent with local or diffuse bladder
      wall thickening with progressive enhancement, and also showed that the bladder
      mucosal lining was nondestructive. Pelvic MRI showed that the local or diffuse
      thickened bladder wall was iso-intense on T1-weighted images, hypo-intense on T2
      weighted images, and slightly restricted on diffusion weighted imaging (DWI) in
      one case. After therapy, the thickened wall of the gastrointestinal tract and
      urinary bladder had improved markedly in the two cases. To the best of our
      knowledge, this is the first report on the radiological imaging of EG and
      coexistent EC by both CT and MRI and the first with DWI findings. 

PMID- 25780318
TI  - Rare cause of appendicitis: Mechanical obstruction due to Fasciolopsis buski
      infestation.
AB  - This study aimed to improve the understanding of the clinical characteristics of
      patients with fasciolopsiasis and thus reduce misdiagnosis and inappropriate
      treatment. We retrospectively analyzed the clinical data of two patients with
      fasciolopsiasis which caused appendicitis. Fasciolopsis buski infestation as a
      cause of appendicitis is very rarely seen in the clinic. The clinical
      characteristics, clinical manifestations, diagnostic methods and the principles
      of treatment in these two patients were analyzed. 

PMID- 25780319
TI  - Adenomas of the common bile duct in familial adenomatous polyposis.
AB  - Familial adenomatous polyposis (FAP) or Gardner's syndrome is often accompanied
      by adenomas of the stomach and duodenum. We experienced a case of adenomas of the
      common bile duct in a 40-year-old woman with FAP presenting with acute
      cholangitis. Only 8 cases of adenomas or adenocarcinoma of the common bile duct
      have been reported in the literature in patients with FAP or Gardner's syndrome.
      Those patients presented with acute cholangitis or pancreatitis. Local excision
      or Whipple procedure may be the reasonable surgical option. 

PMID- 25780320
TI  - Atrial fibrillation and gastroesophageal reflux disease: From the cardiologist
      perspective.
AB  - We have read with interest the paper by Roman C. and colleagues discussing the
      relationship between gastroesophageal reflux disease and atrial fibrillation. The
      review is presenting the available evidence for the common pathogenic mechanisms.
      However, from a cardiologist perspective, some available data were not
      highlighted in the review, cardiovascular involvement in gastroesophageal reflux
      is less assessed. Hypertension, obesity or diabetes mellitus are substrate for
      left atrial remodeling that initiate and sustained atrial fibrillation
      development. One of the pathophysiologic mechanisms in atrial fibrillation is the
      presence of a trigger. Gastroesophageal reflux could be only a trigger for this
      arrhythmia. We believe that atrial fibrillation should be considered as possible
      extraesophageal syndrome in the gastroesophageal reflux classification. 

PMID- 25780321
TI  - Craving is an Affective State and Its Regulation Can Be Understood in Terms of
      the Extended Process Model of Emotion Regulation.

PMID- 25780322
TI  - Surgical, interventional, and device innovations in the management of
      hypertension.
AB  - The prevalence of hypertension around the world has increased significantly with
      projections for an increasing major global burden of hypertension. Medication
      resistant hypertension can be perplexing and frustrating. The existence of these
      difficult patients results in the need for additional approaches to treatment
      including surgery, percutaneous interventions, and device management. The
      sophistication of these techniques has progressed markedly and initial procedures
      such as classical sympathectomy and renal artery bypass are almost never
      performed. Newer techniques of angioplasty with stenting, renal artery
      denervation, and baroreflex activation therapy via electrical stimulation of the
      carotid baroreceptors are now in use with increasing evidence for significant
      benefit. 

PMID- 25780323
TI  - Influence of Access, Anticoagulant, and Bleeding Definition on Outcomes of
      Primary Percutaneous Coronary Intervention: Early Experience of an US Academic
      Center.
AB  - Background We aimed to carry out comparison of different bleeding avoidance
      strategies in doing primary percutaneous coronary intervention (PPCI) using
      either radial or femoral as access of choice and either bivalirudin or
      unfractionated heparin as anticoagulant of choice. In this analysis, we analyzed
      the influence of major bleeding definition on bleeding outcomes as well. Methods
      We did a retrospective analysis of 139 patients with ST-segment elevation
      myocardial infarction (STEMI) who had PPCI in our academic center from January
      2010 till October 2013. The primary outcome at 30 days was a composite of death
      from any cause or stent thrombosis or non-coronary artery bypass grafting (CABG)
      related major bleeding (CathPCI Registry definition) and secondary outcomes were
      individual components of primary outcome and the hospital length of stay. Results
      There was no significant difference among different access/anticoagulant
      combinations with regards to primary outcome (22% in radial/bivalirudin vs. 5% in
      radial/heparin vs. 17% in femoral/bivalirudin vs. 28% in femoral/heparin group; p
      = 0.2) as well as its individual components except the hospital length of stay
      (2.56 vs. 3 vs. 3.97 vs. 4.4 days each; p < 0.0001). The overall rate of major
      bleeding was 11.5%. When we use HORIZON-AMI bleeding definition, it went up to 25
      % due to one particular component (p < 0.004). Conclusions This single center
      observational study doing PPCI did not show any superiority of one bleeding
      avoidance strategy over others with regard to primary outcome and its individual
      components except the hospital length of stay. It also shows the importance of
      bleeding definition on bleeding outcomes. 

PMID- 25780324
TI  - Overcoming aspirin resistance with loading clopidogrel earlier in elective
      percutaneous coronary intervention.
AB  - We aimed to analyze the clinical effect of clopidogrel loading time on adverse
      cardiovascular events among patients with aspirin resistance. Recurrent adverse
      events may still occur despite dual antiplatelet therapy after coronary stenting.
      Aspirin resistance is one of the possible reasons of this trouble. Optimal
      antiplatelet strategy for coronary stenting is unknown among patients with
      aspirin resistance. A total of 980 patients scheduled for elective coronary
      stenting were enrolled and allocated into two groups according to the loading
      time of clopidogrel more or less than 6 hours before coronary intervention (early
      or late-loaded groups, respectively). Aspirin resistance was determined
      according to the urinary levels of 11-dehydrothromboxane B2. Overall 240 patients
      who were allocated to early- and late-loaded groups were identified as aspirin
      resistant according to the urinary levels of 11-dehydrothromboxane B2. After a
      follow-up period of 12 months major adverse cardiac events were observed among 16
      patients (13.9%) in the early-loaded group and 30 patients (25.8%) in the late
      loaded group (p = 0.02). Early loading of clopidogrel was an independent
      predictor of lower rate of cardiac events (hazard ratio = 0.46 [0.32-0.76, 95%
      confidence interval], p = 0.001). The rates of bleeding events and periprocedural
      myocardial infarction were similar in early- and late-loaded groups. The current
      study demonstrated that loading of clopidogrel earlier than 6 hours before
      elective coronary stenting among aspirin-resistant patients was associated with
      increased benefits for ischemic events with similar bleeding rates. 

PMID- 25780325
TI  - A near infrared spectroscopy-based test of calf muscle function in patients with
      peripheral arterial disease.
AB  - Background The study aims to test a new, simple, and reliable apparatus and
      procedure for the diagnostics and treatment evaluation of peripheral arterial
      disease (PAD). The test apparatus involves near infrared spectroscopy (NIRS) of a
      main part of the lower leg muscles during isometric flexion and extension of the
      ankle joint performed with the foot strapped in a specially designed pedal
      ergometer. Design To evaluate the reproducibility of the new test compared with
      an existing testing method of treadmill walking. Methods Eleven patients
      participated in the study: nine patients with claudication and two age-matched
      patients without claudication. Each patient was tested with an isometric
      ergometer pedal test and a treadmill test applying NIRS measurements of the
      anterior tibial and the gastrocnemius muscles (GAS). Tests were repeated three
      times with randomly selected intervals between individual test runs. Intraclass
      correlation constant (ICC) was used to describe reproducibility. The ICC was
      calculated using the area under the NIRS oxygenated hemoglobin (Hbox) curve, the
      initial velocity of the Hbox recovery curve, force measurements, and walking
      time. Results The ICC of the GAS was between 0.92-0.95 (foot-pedal) and 0.70-0.98
      (tread mill) and of the anterior tibial muscle was between 0.87-0.96 (foot-pedal)
      and 0.67-0.79 (tread mill). Conclusion In this study, we contribute a new
      apparatus and test protocol for peripheral arterial disease (PAD) applying NIRS
      technique and controlled physical activity to evaluate the degree of muscle
      oxygenation under specific functionally relevant conditions. Thus, we have
      developed a clinically applicable "easy-to-do" exercise test of patients with
      chronic PAD which show high reproducibility. 

PMID- 25780326
TI  - A novel method to risk stratify patients undergoing exercise stress
      echocardiography using a set of combined criteria.
AB  - Background and Purposes A novel method using quantitative long-axis function and
      tissue Doppler in addition to wall motion analysis in exercise stress
      echocardiography was evaluated. We hypothesized that the novel criteria added
      additional accuracy in stress echocardiography. Methods Patients with chest pain
      and at low-to-intermediate risk for obstructive coronary artery disease (CAD)
      were retrospectively studied. They underwent stress echocardiography with
      attention to wall motion abnormalities, left ventricular long-axis function, and
      tissue Doppler measurement. Results The results showed that the combined novel
      criteria (i.e., classifying a case as positive if three out of the following four
      criteria were fulfilled: (1) abnormal segmental wall motion shortly after peak
      stress; (2) Ee wave after peak stress less than 10 cm/s and Ee/Aa ratio after
      peak stress less than 1; (3) Sm wave after peak stress less than 10.5 cm/s; (4)
      abnormal long-axis left ventricular function) offered a better accuracy for
      predicting obstructive CAD and future revascularization with a high sensitivity
      (100%) and high negative predictive value (100%) . Conclusion From a practical
      standpoint, the combined novel criteria may be useful in improving the diagnostic
      accuracy of stress echocardiography. 

PMID- 25780327
TI  - French Oak Wood (Quercus robur) Extract (Robuvit) in Primary Lymphedema: A
      Supplement, Pilot, Registry Evaluation.
AB  - The aim of this pilot supplement study was the evaluation of an oak wood extract
      (Robuvit, Quercus robur [QR], Horphag Research) in an 8-week registry study on
      lymphatic signs in primary lymphedema. Subjects with primary lymphedema confined
      to a single leg without skin changes or ulcerations were followed for at least 8
      weeks. Lymphedema was mainly present distally (below the knee). Three groups were
      formed: one group used only the standard management for lymphedema; one used the
      same management plus 300 mg Robuvit; and one used the standard management plus
      600 mg of Robuvit. The three groups were comparable. After 8 weeks the variation
      in leg volume was on average -6.2% with standard management, -15% in the QR 300
      mg group, and -18.9% in the 600 mg group. The edema score was also significantly
      lower at 8 weeks in the two QR groups. The variation in proteins in the
      interstitial fluid in comparison with initial values was -14.8% in controls in
      comparison with -29.9% in QR 300 mg group and -36.9% in QR 600 mg group. Skin
      flux significantly improved (increased) in the two QR groups. Ultrasound
      pretibial skin thickness was decreased on average 6% in controls versus 10.3% in
      the low-dose QR group and 11.8% in the higher dose group. Perimalleolar thickness
      was decreased 7% in controls and more in the two QR groups. Ankle circumference
      was decreased 4.4% in controls and more in the two supplement groups. This pilot
      registry indicates that Robuvit can be effective in the management of primary
      lymphedema. More patients and longer evaluation periods are needed. 

PMID- 25780328
TI  - Endovascular management of secondary aortoduodenal fistula: the importance of gut
      restoration.
AB  - Secondary aortoenteric fistula (SAEF) is a rare, life-threatening complication of
      aortic reconstructive surgery. Graft excision associated with gut repair and
      extra-anatomic bypass or in situ aortic reconstruction is the best option.
      However, it is associated with high mortality rates, especially when undertaken
      in unstable patients with severe comorbidities. We present a case of SAEF
      successfully treated by endovascular repair and gut restoration. After
      laparotomy, a dense inflammatory "frozen" mass was found around the involved part
      of the duodenum and the aortic sac. Because of his comorbidities, the difficulty
      in dissection of the aortic sac and the risk of damage in adjacent organs, the
      initial plan for aortic reconstruction was abandoned. A surgical isolation of the
      third portion of the duodenum and a duodenum-jejunal anastomosis were performed.
      An Endurant endograft 32-16-16 mm (Medtronic, Inc., Minneapolis, MN) was
      implanted to achieve aortic continuity. Twenty months postdischarge, the patient
      remains in good general condition, afebrile, and with normal laboratory tests and
      inflammation markers. In high-risk patients, endovascular intervention combined
      with gut repair without further aortic reconstruction can be a permanent solution
      requiring, however, close surveillance. 

PMID- 25780329
TI  - Concomitant anterior and inferior myocardial infarctions.
AB  - Acute multicoronary occlusion is an extremely rare clinical and angiographic
      finding. Prompt diagnosis and treatment are extremely important. Herein, we
      present a 38-year-old man suffering from concomitant anterior and inferior
      myocardial infarctions due to simultaneous total occlusion of both the left
      anterior descending and right coronary arteries. 

PMID- 25780331
TI  - Effect of cilostazol on the p50 of the oxygen-hemoglobin dissociation curve.
AB  - Cilostazol is a drug used for the treatment of intermittent claudication caused
      by narrowing of the blood vessels and reduced oxygen supply, characterized by
      intense pain in the leg when walking. This study was designed to investigate the
      effect of cilostazol on the P50 of the oxygen hemoglobin dissociation curve. A
      total of eight healthy adult subjects were studied. Blood samples (0.5 mL) from
      each subject were mixed with 5, 10, and 20 MUL of the 0.5 mg/mL stock solution of
      cilostazol to give concentrations of 10, 20, and 40 ug/mL equivalent to adult
      doses of 50, 100, and 200 mg, respectively. The control sample had no drug added.
      The oxygen hemoglobin dissociation curve of each sample was plotted and the P50
      determined with a Hemox-Analyzer (TCS, Medical Products Division, Southampton,
      PA). The mean P50 for the control samples was 28.27 +/- 0.43 mm Hg. The values of
      the samples exposed to 10, 20, and 40 ug/mL cilostozol were 29.63 +/- 0.66, 30.15
      +/- 0.77, and 31.66 +/- 0.62 mm Hg, respectively. There was a statistically
      significant difference (p < 0.01) between the control and samples exposed to 40
      ug/mL cilostazol. This study suggests that cilostazol caused an increase in the
      release of oxygen from hemoglobin as shown in the P50 values. This effect was
      significant at the highest concentration of 40 ug/mL. 

PMID- 25780330
TI  - Polyarteritis nodosa-induced pancreaticoduodenal artery aneurysmal rupture.
AB  - Polyarteritis nodosa (PAN) is a systemic, necrotizing vasculitis of small- and
      medium-sized arteries typically with multiorgan involvement. Most cases of PAN
      are idiopathic, although hepatitis B or C virus infections and hairy cell
      leukemia are important in the pathogenesis of some cases. PAN is characterized as
      segmental transmural inflammation of muscular arteries. Diagnosis is based on
      clinical suspicion, a negative immunofluorescence test for antineutrophil
      cytoplasmic antibodies, and whenever possible, biopsy conformation. Angiographic
      images may reveal microaneurysms affecting the renal, hepatic, or mesenteric
      vasculature. Aneurysmal formation and rupture are important complications that
      can be fatal. Treatment may warrant immunosuppression with steroids and
      cyclophosphamide. If left untreated, PAN can be fatal. To our knowledge, we
      report the second documented case of PAN-induced ruptured inferior
      pancreaticoduodenal artery aneurysm. 

PMID- 25780332
TI  - Use of noncontrast computed tomography of the inferior vena cava for real-time
      imaging guidance for the placement of inferior vena cava filters.
AB  - Appropriate placement of an inferior vena cava (IVC) filter necessitates imaging
      of the renal veins because when an IVC filter is deployed its tip should be at or
      below the inferior aspect of the inferiormost renal vein. Traditionally, imaging
      during placement of IVC filters has been with conventional cavography and
      fluoroscopy. Recently, intravascular ultrasound has been used for the same
      purpose but with additional expense. Morbidly obese patients often exceed the
      weight limit of fluoroscopy tables. In addition, short obese patients are at risk
      of falling from narrow fluoroscopy tables. For such patients, computed tomography
      (CT) guidance is a viable alternative to conventional fluoroscopic guidance. IVC
      placement was performed in the CT suite for two obese patients who exceeded the
      weight limits of the available fluoroscopy tables. In one case, a Vena-Tech
      filter (Braun Medical, Melsungen, Germany) was placed using CT fluoroscopy. In
      the second case, a Recovery (Bard, Murray Hill, NJ) filter was placed using
      intermittent limited z-axis scanning. In the first case, the filter was placed
      below the level of the renal veins and above the confluence of the iliac veins,
      which is acceptable placement. In the second case, with refinement of technique,
      the filter tip was placed less than 1 cm below the inferiormost renal vein, which
      is considered optimal placement. CT of the IVC precisely images the renal veins
      and can characterize their number and their confluence with the IVC. CT guidance
      is a viable alternative to fluoroscopic guidance for the placement of IVC filters
      in morbidly obese patients. 

PMID- 25780333
TI  - A novel approach to identify candidate prognostic factors for hepatitis C
      treatment response integrating clinical and viral genetic data.
AB  - The combined therapy of pegylated interferon (IFN) plus ribavirin (RBV) has been
      for a long time the standard treatment for patients infected with hepatitis C
      virus (HCV). In the case of genotype 1, only 38%-48% of patients have a positive
      response to the combined treatment. In previous studies, viral genetic
      information has been occasionally included as a predictor. Here, we consider
      viral genetic variation in addition to 11 clinical and 19 viral populations and
      evolutionary parameters to identify candidate baseline prognostic factors that
      could be involved in the treatment outcome. We obtained potential prognostic
      models for HCV subtypes la and lb in combination as well as separately. We also
      found that viral genetic information is relevant for the combined treatment
      assessment of patients, as the potential prognostic model of joint subtypes
      includes 9 viral-related variables out of 11. Our proposed methodology fully
      characterizes viral genetic information and finds a combination of positions that
      modulate inter-patient variability. 

PMID- 25780334
TI  - Apparent microRNA-Target-specific Histone Modification in Mammalian
      Spermatogenesis.
AB  - BACKGROUND: Epigenetics is an important mRNA expression regulator. However, how
      distinct epigenetic factors, such as microRNAs (miRNAs) and promoter methylation,
      cooperatively regulate mRNA expression is rarely discussed. Recently, apparent
      miRNA regulation of promoter methylation was identified by bioinformatic
      analysis; however, it has not yet been experimentally confirmed. If miRNA
      regulation of other epigenetic factors were identified, it would reveal another
      layer of epigenetic regulation. In this paper, histone modifications (H3K4me1,
      H3K4me3, H3K27me3, H3K27ac, H3K9ac, and H2AZ) during mammalian spermatogenesis
      were studied and the apparent miRNA-target-specific histone modification was
      investigated by bioinformatic analyses of publicly available datasets. RESULTS:
      We identified several miRNAs' target genes that are significantly associated with
      histone modification during mammalian spermatogenesis. MiRNAs that target genes
      associated with the most significant histone modifications are expressed before
      or during spermatogenesis; thus the results were convincing. CONCLUSIONS: In this
      paper, we identified apparent miRNA regulation of histone modifications using a
      bioinformatics approach. The biological mechanisms of this effect should be
      further experimentally investigated.

PMID- 25780335
TI  - Comprehensive evaluation of composite gene features in cancer outcome prediction.
AB  - Owing to the heterogeneous and continuously evolving nature of cancers,
      classifiers based on the expression of individual genes usually do not result in
      robust prediction of cancer outcome. As an alternative, composite gene features
      that combine functionally related genes have been proposed. It is expected that
      such features can be more robust and reproducible since they can capture the
      alterations in relevant biological processes as a whole and may be less sensitive
      to fluctuations in the expression of individual genes. Various algorithms have
      been developed for the identification of composite features and inference of
      composite gene feature activity, which all claim to improve the prediction
      accuracy. However, because of the limitations of test datasets incorporated by
      each individual study and inconsistent test procedures, the results of these
      studies are sometimes conflicting and unproducible. For this reason, it is
      difficult to have a comprehensive understanding of the prediction performance of
      composite gene features, particularly across different cancers, cancer subtypes,
      and cohorts. In this study, we implement various algorithms for the
      identification of composite gene features and their utilization in cancer outcome
      prediction, and perform extensive comparison and evaluation using seven
      microarray datasets covering two cancer types and three different phenotypes. Our
      results show that, while some algorithms outperform others for certain
      classification tasks, no single algorithm consistently outperforms other
      algorithms and individual gene features. 

PMID- 25780336
TI  - Sequencing platform modeling and analysis.

PMID- 25780337
TI  - What Tumor Dynamics Modeling Can Teach us About Exploiting the Stem-Cell View for
      Better Cancer Treatment.
AB  - The cancer stem cell hypothesis is that in human solid cancers, only a small
      proportion of the cells, the cancer stem cells (CSCs), are self-renewing; the
      vast majority of the cancer cells are unable to sustain tumor growth indefinitely
      on their own. In recent years, discoveries have led to the concentration, if not
      isolation, of putative CSCs. The evidence has mounted that CSCs do exist and are
      important. This knowledge may promote better understanding of treatment
      resistance, create opportunities to test agents against CSCs, and open up promise
      for a fresh approach to cancer treatment. The first clinical trials of new anti
      CSC agents are completed, and many others follow. Excitement is mounting that
      this knowledge will lead to major improvements, even breakthroughs, in treating
      cancer. However, exploitation of this phenomenon may be more successful if
      informed by insights into the population dynamics of tumor development. We revive
      some ideas in tumor dynamics modeling to extract some guidance in designing anti
      CSC treatment regimens and the clinical trials that test them. 

PMID- 25780338
TI  - Workplace exercise for control of occupational neck/shoulder disorders: a review
      of prospective studies.
AB  - A review was conducted of prospective studies (1997-2014) examining the efficacy
      of exercise as a workplace intervention to control neck/shoulder pain, symptoms,
      and disability. The review identified 38 relevant studies - 20 were classified
      with positive effects, 13 with null effects, and 5 as inconclusive. Of the
      positive studies, 12 were consistent with Level I evidence, 3 with Level II
      evidence, and 5 with Level IV evidence. Specific resistance training (SRT)
      exercise appeared to be associated with more positive studies (eight Level I
      studies) than other exercise modalities such as general resistance training,
      general physical exercise, stretching, and movement awareness exercises. Studies
      of longer trial duration tended toward more null findings and lower program
      compliance. Evidence for a primary preventive effect of workplace exercise is
      minimal. The findings of this review suggest that workplace exercise can be
      effective as tertiary prevention and therapeutic relief of neck/shoulder
      symptoms, at least over the shorter term. 

PMID- 25780339
TI  - Lack of Correlation between Bristol Stool Scale and Quantitative Bacterial Load
      in Clostridium difficile Infection.
AB  - Decision to test for Clostridium difficile infection (CDI) is usually made when
      patients have loose stools with Bristol stool score of >=5. We aimed to assess
      the relationship between bacterial load of C. difficile and Bristol stool scale,
      as well as stool frequency in stool samples collected from patients infected with
      the organism. Samples were collected at baseline, during therapy, and at the end
      of therapy. Spearman correlation test was used to evaluate these relationships.
      No correlation between Bristol stool scale and fecal load of C. difficile was
      found for both spores and vegetative cells at all time points as counts were
      persistently high (P = non-significant). Weak positive correlations were found
      between stool frequency and fecal load of C. difficile spores and vegetative
      cells (r s = 0.22 and 0.24, P = 0.04 and 0.03, respectively). These findings
      indicate that quantitative colony counts were sufficiently high to detect C.
      difficile, irrespective of stool consistency, and suggest that semiformed stool
      should be sought for the pathogen in symptomatic patients with frequent stools. 

PMID- 25780340
TI  - Molecular and Physiological Factors of Neuroprotection in Hypoxia-tolerant
      Models: Pharmacological Clues for the Treatment of Stroke.
AB  - The naked mole-rat possesses several unique physiological and molecular features
      that underlie their remarkably and exceptional resistance to tissue hypoxia.
      Elevated pattern of Epo, an erythropoietin (Epo) factor; c-fos; vascular
      endothelial growth factor (VEGF); and hypoxia-inducible factors (HIF-1alpha)
      contribute to the adaptive strategy to cope with hypoxic stress. Moreover, the
      naked mole-rat has a lower metabolic rate than any other eutherian mammal of
      comparable size that has been studied. The ability to actively reduce metabolic
      rate represents a strategy widely used in the face of decreased tissue oxygen
      availability. Understanding the different molecular and physiological factors
      that induce metabolic suppression could guide the development of pharmacological
      agents for the clinical management of stroke patient. 

PMID- 25780341
TI  - The Use of Carbon-Fiber-Reinforced (CFR) PEEK Material in Orthopedic Implants: A
      Systematic Review.
AB  - Carbon-fiber-reinforced polyetheretherketone (CFR-PEEK) has been successfully
      used in orthopedic implants. The aim of this systematic review is to investigate
      the properties, technical data, and safety of CFR-PEEK biomaterial and to
      evaluate its potential for new innovation in the design of articulating medical
      devices. A comprehensive search in PubMed and EMBASE was conducted to identify
      articles relevant to the outcomes of CFR-PEEK orthopedic implants. The search was
      also expanded by reviewing the reference sections of selected papers and
      references and benchmark reports provided by content experts. A total of 23
      articles were included in this review. There is limited literature available
      assessing the performance of CFR-PEEK, specifically as an implant material for
      arthroplasty systems. Nevertheless, available studies strongly support CFR-PEEK
      as a promising and suitable material for orthopedic implants because of its
      biocompatibility, material characteristics, and mechanical durability. Future
      studies should continue to investigate CFR-PEEK's potential benefits. 

PMID- 25780342
TI  - Transpopliteal balloon-assisted excimer-laser atherectomy for the treatment of
      chronic femoropopliteal occlusions: feasibility and initial results.
AB  - PURPOSE: Recanalization of chronic total occlusions (CTOs) of the femoropopliteal
      arteries depends on a successful lesion crossing with the guide wire. The aim of
      this retrospective study was to evaluate the safety, feasibility, and the primary
      results of retrograde recanalization of CTOs with balloon-assisted excimer-laser
      atherectomy (ELA) via a transpopliteal approach after failed antegrade attempts.
      METHODS: A total number of 15 patients (10 male, 5 female) with a mean age of
      68.5 years (range: 43-91 years) treated with retrograde transpopliteal ELA in the
      years 2009-2012 were included retrospectively. After unsuccessful antegrade
      recanalization attempts with conventional guide wires and catheters, patients
      were treated with a retrograde recanalization attempt via a transpopliteal access
      using an excimer laser, followed by pressure-only balloon angioplasty (POBA). The
      mean length of the CTOs in the femoropopliteal arteries was 17.8 +/- 5.4 cm
      (range: 9-29 cm). RESULTS: Technically successful recanalization was achieved in
      14 of 15 patients. Provisional stenting was done in two cases. There were no
      major adverse events regarding the laser atherectomy or popliteal access site.
      One acute reocclusion was observed in the first 48 hours after intervention. The
      ankle-brachial Index increased from preinterventional 0.45 +/- 0.07 to 0.77 +/-
      0.29 (P < 0.05) in the follow-up period (1.5 months), resulting in a primary
      patency of 80%. CONCLUSION: The retrograde ELA for recanalization of chronic
      femoropopliteal occlusions via a popliteal access turned out to be a safe and
      effective procedure with promising primary results. Thus it may be an
      endovascular treatment option for long chronic occlusions after failed antegrade
      recanalization or in patients who are not suitable for surgery.

PMID- 25780343
TI  - Echocardiographic manifestation of esophagitis mimicking a posterior mediastinal
      mass.
AB  - Incidental extracardiac findings (ECFs) are commonly noted on cardiac imaging.
      The majority of the ECFs are noticed on computed tomography (CT), cardiac
      magnetic resonance scanning, and myocardial perfusion imaging. Although
      transthoracic echocardiography (TTE) is a widely used cardiac modality, there is
      scarcity of data describing ECF on TTE. ECFs have the potential to alter patient
      management. We present a rare case of a cystic mass seen in the posterior
      mediastinum on TTE, which led to further evaluation and diagnosis of esophagitis
      with ulceration. 

PMID- 25780345
TI  - Life threatening hemoperitoneum and liver injury as a result of chest tube
      thoracostomy.
AB  - Common complications of chest tube thoracostomy (CTT) include lung laceration,
      chest wall bleeding, improper position of tube, subcutaneous emphysema, and so
      on. Although intra-abdominal injury because of CTT was possible in stomach,
      spleen, and liver, published reports are rare and no case of life-threatening
      hemoperitoneum because of CTT has been published in the literature. Here, we
      present a rare case of life-threatening hemoperitoneum and liver injury because
      of CTT. We successfully treated the case with emergent laparotomy. Owing to great
      rarity and particular rare complication of CTT, we report this case with a review
      of literature. 

PMID- 25780344
TI  - Characterizing heart failure in the ventricular volume domain.
AB  - Heart failure (HF) may be accompanied by considerable alterations of left
      ventricular (LV) volume, depending on the particular phenotype. Two major types
      of HF have been identified, although heterogeneity within each category may be
      considerable. All variants of HF show substantially elevated LV filling
      pressures, which tend to induce changes in LV size and shape. Yet, one type of HF
      is characterized by near-normal values for LV end-diastolic volume (EDV) and even
      a smaller end-systolic volume (ESV) than in matched groups of persons without
      cardiac disease. Furthermore, accumulating evidence indicates that, both in terms
      of shape and size, in men and women, the heart reacts differently to adaptive
      stimuli as well as to certain pharmacological interventions. Adjustments of ESV
      and EDV such as in HF patients are associated with (reverse) remodeling
      mechanisms. Therefore, it is logical to analyze HF subtypes in a graphical
      representation that relates ESV to EDV. Following this route, one may expect that
      the two major phenotypes of HF are identified as distinct entities localized in
      different areas of the LV volume domain. The precise coordinates of this position
      imply unique characteristics in terms of the actual operating point for LV volume
      regulation. Evidently, ejection fraction (EF; equal to 1 minus the ratio of ESV
      and EDV) carries little information within the LV volume representation. Thus
      far, classification of HF is based on information regarding EF combined with EDV.
      Our analysis shows that ESV in the two HF groups follows different patterns in
      dependency of EDV. This observation suggests that a superior HF classification
      system should primarily be founded on information embodied by ESV. 

PMID- 25780346
TI  - Three Adult Cases of HPV-B19 Infection with Concomitant Leukopenia and Low
      Platelet Counts.
AB  - We encountered three adult patients with flu-like symptoms diagnosed with human
      parvovirus B19 (HPV-B19) infection. Blood serum analysis also revealed
      leukopenia, with white blood cell counts (WBCs) of 1,000-2,000/mL and low
      platelet counts of 89-150 * 10(9)/L. Typical skin rash was absent in one patient.
      Bone marrow examination of another patient showed hypoplastic marrow with <5%
      blast cells. All patients recovered without administration of granulocyte colony
      stimulating factor (G-CSF). Therefore, HPV-B19 infection with leukopenia should
      be considered in adult patients with leukopenia during erythema infectiosum
      epidemics, even if typical clinical findings (ie, skin rash) are absent. Further,
      the fact that three cases were observed over the stated time period at our
      hospital, which is located in Nagoya city, showed a transition to a slightly
      higher level of incidence than the annual average. 

PMID- 25780347
TI  - Relative adrenal insufficiency in cirrhotic patients.
AB  - Relative adrenal insufficiency (RAI) was demonstrated in patients with cirrhosis
      and liver failure. A relationship appears to exist between the severity of the
      liver disease and the presence of RAI. Neither the mechanism nor the exact
      prevalence of RAI is fully understood. There is though a hypothesis that low high
      density lipoprotein (HDL) levels in this group of patients may be responsible for
      the insufficiency of cortisol. Several questions also arise about the way and the
      kind of cortisol (total cortisol, free cortisol, or even salivary cortisol) that
      should be measured. The presence of RAI in patients with cirrhosis is
      unquestionable, but still several studies should come up in order to properly
      define it and fully understand it. 

PMID- 25780348
TI  - Development of Interpretable Predictive Models for BPH and Prostate Cancer.
AB  - BACKGROUND: Traditional methods for deciding whether to recommend a patient for a
      prostate biopsy are based on cut-off levels of stand-alone markers such as
      prostate-specific antigen (PSA) or any of its derivatives. However, in the last
      decade we have seen the increasing use of predictive models that combine, in a
      non-linear manner, several predictives that are better able to predict prostate
      cancer (PC), but these fail to help the clinician to distinguish between PC and
      benign prostate hyperplasia (BPH) patients. We construct two new models that are
      capable of predicting both PC and BPH. METHODS: An observational study was
      performed on 150 patients with PSA >=3 ng/mL and age >50 years. We built a
      decision tree and a logistic regression model, validated with the leave-one-out
      methodology, in order to predict PC or BPH, or reject both. RESULTS: Statistical
      dependence with PC and BPH was found for prostate volume (P-value < 0.001), PSA
      (P-value < 0.001), international prostate symptom score (IPSS; P-value < 0.001),
      digital rectal examination (DRE; P-value < 0.001), age (P-value < 0.002),
      antecedents (P-value < 0.006), and meat consumption (P-value < 0.08). The two
      predictive models that were constructed selected a subset of these, namely,
      volume, PSA, DRE, and IPSS, obtaining an area under the ROC curve (AUC) between
      72% and 80% for both PC and BPH prediction. CONCLUSION: PSA and volume together
      help to build predictive models that accurately distinguish among PC, BPH, and
      patients without any of these pathologies. Our decision tree and logistic
      regression models outperform the AUC obtained in the compared studies. Using
      these models as decision support, the number of unnecessary biopsies might be
      significantly reduced.

PMID- 25780349
TI  - Incidence and outcome of contrast-associated acute kidney injury assessed with
      Risk, Injury, Failure, Loss, and End-stage kidney disease (RIFLE) criteria in
      critically ill patients of medical and surgical intensive care units: a
      retrospective study.
AB  - BACKGROUND: Contrast medium used for radiologic tests can decrease renal
      function. However there have been few studies on contrast-associated acute kidney
      injury in intensive care unit (ICU) patients. The objective of this study was to
      evaluate the incidence, characteristics, and outcome of contrast-associated acute
      kidney injury (CA-AKI) patients using the Risk, Injury, Failure, Loss, and End
      stage kidney disease (RIFLE) criteria in critically ill patients in the ICU.
      METHODS: We conducted a retrospective study of adult patients who underwent
      contrast-enhanced radiologic tests from January 2011 to December 2012 in a 30-bed
      medical ICU and a 24-bed surgical ICU. RESULTS: The study included 335 patients,
      and the incidence of CA-AKI was 15.5%. The serum creatinine and estimated
      glomerular filtration rate values in the CA-AKI patients did not recover even at
      discharge from the hospital compared with the values prior to the contrast use.
      Among 52 CA-AKI patients, 55.8% (n = 29) had pre-existing kidney injury and 44.2%
      (n = 23) did not. The CA-AKI patients were divided into risk (31%), injury (31%),
      and failure (38%) by the RIFLE classification. The percentage of patients in whom
      AKI progressed to a more severe form (failure, loss, end-stage kidney disease)
      increased from 38% to 45% during the hospital stay, and the recovery rate of AKI
      was 17% at the time of hospital discharge. Because the Acute Physiology and
      Chronic Health Evaluation (APACHE) II score was the only significant variable
      inducing CA-AKI, higher APACHE II scores were associated with a higher risk of CA
      AKI. The ICU and hospital mortality of patients with CA-AKI was significantly
      higher than in patients without CA-AKI. CONCLUSIONS: CA-AKI is associated with
      increases in hospital mortality, and can be predicted by the APACHE score. TRIAL
      REGISTRATION: NCT01807195 on March. 06. 2013.

PMID- 25780351
TI  - An instrument for broadened risk assessment in antenatal health care including
      non-medical issues.
AB  - INTRODUCTION: Growing evidence on the risk contributing role of non-medical
      factors on pregnancy outcomes urged for a new approach in early antenatal risk
      selection. The evidence invites to more integration, in particular between the
      clinical working area and the public health domain. We developed a non-invasive,
      standardized instrument for comprehensive antenatal risk assessment. The current
      study presents the application-oriented development of a risk screening
      instrument for early antenatal detection of risk factors and tailored prevention
      in an integrated care setting. METHODS: A review of published instruments
      complemented with evidence from cohort studies. Selection and standardization of
      risk factors associated with small for gestational age, preterm birth, congenital
      anomalies and perinatal mortality. Risk factors were weighted to obtain a
      cumulative risk score. Responses were then connected to corresponding care
      pathways. A cumulative risk threshold was defined, which can be adapted to the
      population and the availability of preventive facilities. A score above the
      threshold implies multidisciplinary consultation between caregivers. RESULTS: The
      resulting digital score card consisted of 70 items, subdivided into four non
      medical and two medical domains. Weighing of risk factors was based on existing
      evidence. Pilot-evidence from a cohort of 218 pregnancies in a multi-practice
      urban setting showed a cut-off of 16 points would imply 20% of all pregnant women
      to be assessed in a multidisciplinary setting. A total of 28 care pathways were
      defined. CONCLUSION: The resulting score card is a universal risk screening
      instrument which incorporates recent evidence on non-medical risk factors for
      adverse pregnancy outcomes and enables systematic risk management in an
      integrated antenatal health care setting.

PMID- 25780352
TI  - Prevalence and risk factors of Otitis Media with effusion in school children in
      Qassim Region of Saudi Arabia.
AB  - OBJECTIVE: To determine the prevalence of otitis media with effusion (OME) among
      school children in Qassim region of Kingdom of Saudi Arabia and to determine
      relevant risk factors in affected children. METHODS: Through a cross-sectional
      study, 1488 children in the age range 6-12 years were randomly selected from 25
      primary schools in Qassim region. A questionnaire was used to determine risk
      factors for OME. Otoscopy and tympanometry were used to diagnose and confirm OME.
      Pure tone average for children with confirmed OME was measured. Teachers of
      children were asked to complete a questionnaire evaluating child's level of
      school performance. RESULTS: Prevalence of OME in the study population was 7.5%
      (112/1488). In univariate analysis, it was strongly associated with age less than
      8 years (p< 0.0001; OR= 4.23, 95% CI: 2.85-6.29 ), family size more than 4
      members in the household((p<0.0001; OR= 4.45, 95% CI: 2.23-8.88), mother
      education less than secondary school education (p<0.0001; OR=2.2, 95% CI: 1.47
      3.29), recurrent acute otitis media (AOM) (p<0.0001; OR=5.73, 95% CI: 3.47-9.45),
      and hearing loss symptom (p< 0.0001; OR= 3.39, 95% CI: 1.92-5.99). It is less
      strongly associated with history of preschool AOM (p= 0.002; OR= 3.15, 95% CI:
      1.67-5.97), nasal discharge (p= 0.003; OR= 1.91, 95% CI: 1.24-2.93) and snoring
      (p=0.03; OR= 1.76, 95% CI: 1.06-2.94). OME was significantly higher in schools
      located in rural districts (p<0.001, OR= 2.82, 95% CI: 1.86-4.28). In
      multivariate regression model, five of these factors were found to be predictors
      of OME: age less than 8 years (OR= 5.052, 95% CI:3.289-7.762), family size more
      than4 members in the household) (OR= 4.192, 95% CI: 2.033-8.643), rural school
      district (OR=3.037, 95% CI: 1.933-4.772), mother education lower than secondary
      school education) (OR=2.041, 95% CI:1.602-3.877) and recurrent AOM (OR=4.914, 95%
      CI: 2.677-9.02). Children with OME tend to have poorer school performance
      compared to normal children (p=0.067). No significant correlation was found
      between OME and type of feeding during the first two years of life (p=0.62; OR=
      0.87, 95% CI: 0.51-1.49), preschool daycare attendance (p=0.17; OR= 0.71, 95% CI:
      0.44-1.16), home exposure to cigarette smoke (p=0.4; OR= 1.34, 95% CI:0.68-2.65),
      visits to ENT clinic (p=0.13; OR= 0.58, 95% CI:0.29-1.18), and ENT operations
      (p=0.12; OR= 0.46, 95% CI: 0.17-1.27). CONCLUSION: Prevalence of OME in Qassim
      region reaches 7.5% in school children. Age less than 8 years, family size more
      than 4 members in the household, mother education less than secondary school
      education, living in rural area and recurrent AOM are found to be predictors of
      OME in Qassim region. In this population of children, otoscopy and tympanometry
      should be used as screening tools for OME.

PMID- 25780353
TI  - Atlas and axis injuries role of Halovest.
AB  - BACKGROUND: The literature regarding the different patterns of atlas and axis
      injuries and their appropriate management and the progressive development in the
      management of these injuries is scarce from our world, so we presenting here our
      experience of management of these injuries by applying Halovest. MATERIALS AND
      METHODS: Thirty patients (22 males, 8 females) with atlas and axis injuries were
      treated and then followed-up for an average of 24 months. The data was analysed
      with respect to type of injury and use of Halovest in the treatment of these
      injuries. The patients with neuro defecit were scored as per ASIA grading scale
      (from Grade A to Grade E). RESULTS: The halo-vest immobilization was used for a
      mean period of 12 +/- 3weeks (range 9 to 15 weeks) for atlas and axis injuries.
      Four patients had neurodeficit. Two patients recovered from ASIA Grade C to ASIA
      Grade D. One patient improved from ASIA grade D to ASIA grade E while as one
      patient with neurodeficit was lost to follow up. No death or worsening of the
      neurodeficit was observed during the follow up period. CONCLUSION: The clinical
      as well as radiological outcome of these injuries is mostly satisfactory with the
      conservative management using Halovest. More studies should be conducted to form
      the guidelines regarding patient selection for conservative management using
      halovest.

PMID- 25780354
TI  - Erectile Dysfunction and Other Sexual Activity Dysfunctions among Saudi Type 2
      Diabetic Patients.
AB  - OBJECTIVES: The aim of the study is to determine the prevalence of Erectile
      Dysfunction (ED) in Type 2 diabetic Saudi patients, to determine the effect of
      Type 2 diabetic on other sexual activities (intercourse satisfaction, orgasmic
      function, sexual desire, overall satisfaction), and to assess whether glycemic
      control and duration of diabetes have an influence on sexual activities or not.
      METHODS: A cross-sectional study was conducted among 376 of Type 2 diabetic male
      Saudi patients. Erectile dysfunction and other sexual activities dysfunctions
      were evaluated using the International Index of Erectile Function (IIEF) by a
      fill coded questionnaire. Additionally, the level of glycosylated hemoglobin was
      measured to classify the diabetes control status in patients. RESULTS: Erectile
      Dysfunction was reported by 83% of male Saudi diabetic patients. The results show
      that there was a significant association between the presence of ED and both the
      age and the duration of diabetes. Family income, occupation, and educational
      level of the patients show a significant association between them and erectile
      dysfunction (ED). Moreover, glycemic control did not show a significant
      association with ED in our sample. CONCLUSION: The findings showed that
      prevalence of ED among male Saudi diabetic patients is high. It increases with
      age and duration of diabetes. Also, the study showed that the glycemic control
      did not correlate with ED. It is recommended that the family physician and
      diabetologist should ask routinely for this complication in patients with
      diabetes just like any other diabetes complication.

PMID- 25780355
TI  - Laser micro-grooved, Arginine-Glycine-Apspartic acid (RGD) coated dental
      implants, a 5 years radiographic follow-up.
AB  - OBJECTIVES: This work has utilized laser direct writing to produce 10 microns
      wide uniform grooves on the surface of custom made titanium (Ti-6Al-4V) dental
      implants, and the tri-peptide RGD coating to produce a micromechanical and a
      chemical union with the tissues around the implant crest module and minimize
      crestal bone loss. The aim of this study was to follow these implants
      radiographically after five years of service under a mandibular overdenture.
      METHODOLOGY: Standardized digital periapical radiographs and the computer
      software "Image J" were used to evaluate the bone density profile and vertical
      bone loss along the mesial and distal sides of the implants used in this study.
      RESULTS: The results of this study demonstrated less vertical bone loss and
      higher bone density profiles next to the laser microgrooved implants coated with
      the RGD than those only having the laser micro-grooves. CONCLUSION: The RGD
      coating has improved the bone density profile and reduced the vertical bone loss
      around the studied dental implants. However, further studies are needed to
      compare the effects of the laser micro-grooves versus other uniform or non
      uniform surface features; also, the RGD coating should be compared to other
      biomimetic surface coating materials.

PMID- 25780356
TI  - Levels of adult patients' satisfaction with nursing care in selected public
      hospitals in ethiopia.
AB  - OBJECTIVE: To assess level of adult patients' satisfaction and associated factors
      in nursing care provided in selected public hospitals in Ethiopia. METHODS: A
      cross sectional institution based study was conducted on 582 randomly selected
      patients admitted for at least two nights in three wards of selected public
      hospitals in Eastern Ethiopia. Patients were interviewed face to face using the
      adapted Newcastle Satisfaction with Nursing Scales (NSNS) at the time of their
      discharge. Data was analyzed using SPSS V 16. RESULT: More than half of the
      respondents, 307(52.75%), were satisfied with the nursing care they received. The
      patient satisfaction was found to be 62.71%, 55.67%, 44.85% and 55.15% for
      nursing characteristics, the caring activities, the amount of information given
      and the entire caring environment respectively. Previous history of admission,
      patients' income level, and type of admission rooms have been found to
      significantly affect overall satisfaction of patients. CONCLUSION: The overall
      level of adult patients' satisfaction was moderate. The hospitals should consider
      mechanisms to improve the nurses' communication skills and interpersonal
      relationships beyond training on direct patient care.

PMID- 25780357
TI  - Clinical and radiographic evaluation of copolymerized Polylactic/polyglycolic
      acids as a bone filler in combination with a cellular dermal matrix graft around
      immediate implants.
AB  - OBJECTIVE: This study was conducted to evaluate clinically and radiographically
      the use of a cellular dermal matrix allograft (Alloderm) in combination with
      PLA/PGA (Fisiograft) around immediate implants. MATERIALS AND METHODS: Fourteen
      patients were included in this study, three patients received two implants, total
      of seventeen implants were placed. Periapical radiographs and orthopantomographs
      were taken. The selected teeth were extracted atraumatically after the reflection
      of full thickness flaps. One-piece Zimmer implants were placed immediately into
      the sockets. Weeks from implantation, radiographic evaluation was made at 6
      Fisiograft in powder form was placed in the osseous defects around the implants.
      The implants were immediately restored with provisional crowns free from
      occlusion. Patients were clinically evaluated at 3, 6, and 14 months after
      loading which was done after 6 weeks from implantation. Radiographic evaluation
      was made at 6 and 14 months from implant placement. RESULTS: showed that
      immediate implantation was successful in sixteen out of seventeen implants,
      clinical parameters regarding plaque index, gingival index, there was a slight
      decrease through the follow-up periods from 3 to 14 months but it was non
      significant, while there was a significant decrease in the probing depth.
      Radiographically there was a significant increase in the bone density from 6 to
      14 months post loading, while the vertical bone defect was significantly
      decreased. The fisiograft functioned well as space maker and scaffolding
      material. The Alloderm performed well as a membrane to be used in association
      with immediate implants and it has a good potentiality for increasing the width
      of the keratinized gingiva, which is an important feature for implant esthetics.
      CONCLUSION: the combination technique between the bone graft and the membrane
      proved to be successful to overcome dehiscence and osseous defects around
      immediate implants.

PMID- 25780358
TI  - Effects of chocolate intake on Perceived Stress; a Controlled Clinical Study.
AB  - BACKGROUND: Cocoa polyphenols have been shown to reduce stress in highly
      stressed, as well as normal healthy individuals, we wondered whether commercially
      available chocolate could reduce perceived stress in medical students or not, so
      we decided to conduct this study. METHODS: Sixty students were divided into 3
      groups (10 males + 10 females/group): i) Dark chocolate (DC) ii) Milk chocolate
      (MC) iii) White chocolate (WC). Subjects answered a PSS-10 (Perceived Stress
      Scale) questionnaire at baseline and after consumption of chocolate (40 g/day)
      for 2 weeks. Data were analyzed by using Microsoft Excel and SPSS version 20.
      Descriptive analyses were conducted. Means were compared across the study groups
      by One-Way ANOVA and within the same group by paired 't' test. RESULTS: Mean
      stress scores compared between the groups by ANOVA revealed statistically not
      significant differences before (F =0.505; P=0.606) and after chocolate
      consumption (F=0.188; P=0.829). Paired 't' test compared stress scores means
      before and after chocolate supplementation within the same group and exhibited
      statistically significant decrease in DC (t = 2.341; p value = 0.03) and MC (t =
      3.302; p value = 0.004) groups. Mean stress scores decreased, on average, by
      approximately 2 and 3 points in DC and MC groups, respectively, at 95% Confidence
      Interval. The difference was more evident and statistically significant in female
      students as compared to the males. CONCLUSION: Consumption of 40 g of Dark and
      Milk chocolate daily during a period of 2 weeks appear to be an effective way to
      reduce perceived stress in females.

PMID- 25780359
TI  - Selected enteropathogens and clinical course in children hospitalized with severe
      acute gastroenteritis in Barbados.
AB  - OBJECTIVES: The primary aim of this study was to determine the prevalence of
      selected bacterial and viral enteropathogens in children hospitalized with acute
      gastroenteritis and the secondary aim was to characterize the clinical course and
      the outcome. METHODOLOGY: A retrospective audit of children (<15 years) admitted
      with acute gastroenteritis during January 2008 to October 2010. Stool samples
      were analyzed for bacterial pathogens and for the Rotavirus. Demographics,
      clinical presentations, hospital course and outcome were extracted from the
      admission records. RESULTS: There were 571 children hospitalized with acute
      gastroenteritis, which accounted for 11% of all medical hospitalization in
      children. Overall, 42.9% of these children were <=12 months in age. Stool test
      result was documented in 46.6% of children hospitalized with gastroenteritis and
      an enteropathogen was isolated in 36.8% of cases with documented stool test
      result. Non-typhoidal Salmonella species was the most commonly isolated
      enteropathogen accounting for 21.1% of all the documented cases. Rotavirus was
      identified as an etiological agent in 9.0%. Of the 56 children who had non
      typhoidal salmonella gastroenteritis, 54(96.4%) were younger than 5 years. The
      median duration of hospitalization was 2 days (Range 1 day to 9 days). There were
      no deaths. CONCLUSION: Non-typhoidal salmonella was the most common
      enteropathogen isolated and this was followed by the Rotavirus.

PMID- 25780360
TI  - Novel configuration of laryngeal mask airway.
AB  - OBJECTIVES: Hospital airway emergency teams are often responsible for responding
      to codes, emergency intubations etc. The individual provider may have to respond
      quickly to widely separated areas of large medical centers on a moment's notice.
      Further, in addition to the urgency, the distance of different sites makes it
      important that the airway team not have to lug a large medical gear bag with
      airway supplies and emergency drugs. While the importance of the LMA in emergency
      airway management has been well established, it is sold as a fairly bulky device
      that requires a disproportionate space in an airway pack. We sought to examine
      whether modifying the LMA packaging might reduce the amount of space taken up by
      the need to carry three different sizes in an airway pack. METHODS: A commonly
      used Laryngeal Mask Size Number 3 manufactured by Ambu Company was studied. The
      volume displacement of the package, and then just the LMA was measured using
      volumetric techniques. RESULTS: Removing the large packaging yielded a much
      smaller footprint in cubic ml that was only 18% of the original packaging: 43
      versus 240 cubic milliliters. CONCLUSIONS: This configuration of LMA transport
      allows for transporting more airway equipment in less space. These results have
      important implications for emergency airway response teams. Removing the original
      packaging and using this folded-over configuration allows to use 82% less volume
      in cubic milliliters per LMA in the airway pack. This allows emergency teams to
      carry more equipment in much less space.

PMID- 25780361
TI  - Management of pulp canal obliteration using the Modified-Tip instrument
      technique.
AB  - The incidence of pulp canal obliteration following dental trauma has been
      reported to be approximately 4 - 24% and its management can be quite challenging
      for the practitioner. Locating the canal and negotiating it to full working
      length may lead to iatrogenic errors such as fractured instrument and
      perforation. This case report deals with such a case using the modified tip
      instrument technique to gain access and negotiate the canal to the apex followed
      by conventional root canal preparation and obturation. 

PMID- 25780362
TI  - A 94-year-old man with recurrent hypoglycemia caused by non-islet cell tumor
      hypoglycemia (NICTH).
AB  - Non-islet cell tumor hypoglycemia (NICTH) is a rare but serious paraneoplastic
      syndrome in which a tumor secretes the high molecular weight form of IGF-II,
      causing hypoglycemia and requiring early diagnosis and management. Here, I report
      a rare case of NICTH caused by fibrosarcoma in a 94-year-old male with recurrent
      hypoglycemia. This case report describes the clinical presentation and diagnostic
      and management issues involved in a case of NICTH that was diagnosed at a
      tertiary care institute. 

PMID- 25780363
TI  - Cutaneous Rosai-Dorfman Disease presenting as a flank swelling.
AB  - Rosai-Dorfman disease (RDD) is primarily a disease of lymph nodes caused by
      accumulation of excessive histiocytes. The extra-nodal sites are simultaneously
      involved in almost half the cases. However, presentation with isolated extra
      nodal sites is uncommon and disease confined to skin and soft tissues is a rare
      entity. We report RDD in a 33 year old man who presented as a flank mass and was
      a diagnostic challenge for the surgical team. This case report strengthens the
      evidence that RDD should be added to the list of rare causes of skin and soft
      tissue swellings and informs how to manage such patients. 

PMID- 25780364
TI  - Renomedullary Interstitial Cell tumor in a young lady: An incidental autopsy
      finding: A case report.
AB  - Renomedullary interstitial cell tumor (RMICT) is a rare benign tumor of the
      kidney. It is usually detected incidentally at autopsies. It occurs commonly in
      patients above 50 years of age. This lesion is most of the times small,
      asymptomatic and not detected clinically. We report a case of incidental
      detection of this tumor at autopsy of a young female patient. 

PMID- 25780365
TI  - Health risks associated with mobile phones use.

PMID- 25780366
TI  - Psychological assessment of mothers and their daughters at the time of diagnosis
      of precocious puberty.
AB  - BACKGROUND: Concerns about psychological distress are often used to justify
      treatment of girls with precocious puberty, but there is little evidence to
      support these concerns. The extent to which psychological problems are associated
      with central precocious puberty (CPP) compared with other forms of early puberty
      in girls has likewise not been established. METHODS: Girls presenting with
      untreated CPP, premature adrenarche (PA) or early normal puberty (ENP) were
      recruited from our pediatric endocrine clinic along with their mothers. Child
      psychological adjustment was assessed by child self-report and parent report.
      Parent self-reported personality, anxiety, and depression were also assessed.
      Differences between groups were explored using one-way ANOVA and Dunnett's T3
      test. RESULTS: Sixty-two subjects (aged 7.5 +/- 1.4 years, range 4.8-10.5) were
      enrolled, of whom 19 had CPP, 22 had PA, and 21 had ENP. Girls with ENP were
      significantly older (8.9 +/- .9 years) than girls with CPP (6.9 +/- 1.1 years, p
      < .001) and PA (6.6 +/- 1.0 years, p < .001). Girls with PA had significantly
      higher BMI z-scores (1.7 +/- .8) than girls with CPP (1.1 +/- .6, p = .01) and
      ENP (1.2 +/- .6, p = .04). More girls with PA and ENP were from racial minorities
      (47% and 50% respectively) than girls with CPP (32%). No group differences were
      found for any child measure of psychological adjustment. However, mothers of
      girls with PA scored significantly higher than mothers of girls with ENP on one
      measure of depression (p = .04) and stress (p = .01). CONCLUSIONS: While mothers
      of girls with PA report increased psychological distress on some measures, no
      differences in psychological adjustment were found at baseline amongst the girls
      themselves. Whether these results will change as puberty progresses in the PA and
      ENP groups or with treatment of CPP is unknown. Long-term prospective studies are
      needed in order to further investigate psychological correlates of early puberty
      in girls.

PMID- 25780367
TI  - Congenital nystagmus and central hypothyroidism.
AB  - We observed a male newborn with bilateral nystagmus and central hypothyroidism
      without hypoprolactinemia due to a deletion of chromosome band Xq26.1q26.2,
      containing FRMD7 and IGSF1. These two loss-of function mutations are known to
      cause, respectively, congenital nystagmus and the ensemble of central
      hypothyroidism, hypoprolactinemia and testicular enlargement. These latter two
      features may not yet be present in early life. 

PMID- 25780368
TI  - Congenital adrenal hyperplasia patient perception of 'disorders of sex
      development' nomenclature.
AB  - BACKGROUND: As the benefits of patient-centered care have become more widely
      recognized, it is important to understand patients' sentiments regarding aspects
      affecting their care. In an effort to display more sensitivity to patient
      concerns, the term "disorders of sex development" (DSD) was proposed in 2006 as
      new nomenclature to replace older terms that were considered to have negative
      connotations. METHODS: The objective of the study was to examine the views of
      congenital adrenal hyperplasia (CAH) patients and their caregivers regarding the
      new nomenclature. The study was observational to evaluate the views of the CAH
      community, and the primary endpoint was perception of the term DSD. The study was
      conducted as a survey about views regarding DSD nomenclature. The survey was sent
      via email to eligible subjects. Along with a short introduction explaining the
      term DSD, the survey was sent to eligible CAH patients and their caregivers. 589
      CAH patients or family members participated in the survey. RESULTS: A total of
      589 responses were received (255 classical females, 104 non-classical females,
      174 males, 56 not specified) (547 U.S., 42 international) (128 CAH patients, 408
      parents or other family members). 70.6% had never heard the term DSD. 71.0%
      disliked or strongly disliked the term DSD. 83.6% stated they did not identify
      with the term DSD. 76.0% felt that the term DSD has a negative effect on the CAH
      community. There was no significant difference in opinion of DSD between
      classical females and other CAH patients, between US and international, between
      surgical and non-surgical patients, or between patients and parents. There was no
      correlation with patient age. CONCLUSIONS: Our results indicate that the majority
      of parents and patients with CAH are dissatisfied with the term DSD. Our results
      highlight the challenges within the field of DSD to reach a consensus regarding a
      sensitive topic and to bridge the gap between current medical practice and
      patient satisfaction. It is the authors' belief that reconsideration of the
      current nomenclature and ongoing dialogue between the medical community and
      patients will eventually lead to removal of stigmatization, better management
      protocols, and improved outcomes.

PMID- 25780369
TI  - Horizons of psychiatric genetics and epigenetics: where are we and where are we
      heading?
AB  - Today multinational studies using genome-wide association scan (GWAS) for
      >1000,000 polymorphisms on >100,000 cases with major psychiatric diseases versus
      controls, combined with next-generation sequencing have found ~100 genetic
      polymorphisms associated with schizophrenia (SCZ), bipolar disorder (BD), autism,
      attention deficit and hyperactivity disorder (ADHD), etc. However, the effect
      size of each genetic mutation has been generally low (<1%), and altogether could
      portray a tiny fraction of these mental diseases. Furthermore, none of these
      polymorphisms was specific to disease phenotypes indicating that they are simply
      genetic risk factors rather than causal mutations. The lack of identification of
      the major gene(s) in huge genetic studies increased the tendency for reexamining
      the roles of environmental factors in psychiatric and other complex diseases.
      However, this time at cellular/molecular levels mediated by epigenetic mechanisms
      that are heritable, but reversible while interacting with the environment. Now,
      gene-specific or whole-genome epigenetic analyses have introduced hundreds of
      aberrant epigenetic marks in the blood or brain of individuals with psychiatric
      diseases that include aberrations in DNA methylation, histone modifications and
      microRNA expression. Interestingly, most of the current psychiatric drugs such as
      valproate, lithium, antidepressants, antipsychotics and even electroconvulsive
      therapy (ECT) modulate epigenetic codes. The existing data indicate that, the
      impacts of environment/nurture, including the uterine milieu and early-life
      events might be more significant than genetic/nature in most psychiatric
      diseases. The lack of significant results in large-scale genetic studies led to
      revise the bolded roles of genetics and now we are at the turning point of
      genomics for reconsidering environmental factors that through epigenetic
      mechanisms may impact the brain development/functions causing disease phenotypes.

PMID- 25780370
TI  - Sulfur Mustard Effects on Mental Health and Quality-of-Life: A Review.
AB  - OBJECTIVE: Mental disorders are more common among the chemically injured veterans
      rather the than the normal population. The main aim of this study was to evaluate
      the effects of mustard gas (MG) on mental health and quality-of-life (QOL) in the
      people exposed to it based on reviewing valid published articles. METHODS: We
      searched English databases including Medline, ISI and Scopus as well as Farsi
      databases including Iranmedex and Irandoc and reviewed them. The used keywords
      were in two English and Farsi languages. Forty related full texts out of more
      than 300 articles were assessed and for their qualification, only the
      publications in accredited journals were considered sufficient. RESULTS: The
      average mental health score of victims using the general health questionnaire
      (GHQ) was 48.92. The frequency of anxiety was (18-65%), insomnia (13.63%), social
      performance disturbances (10.73%), severe depression (6-46%), low concentration
      (54%), emotional problems (98%), behavioral abnormalities (80%), thought
      processing disturbances (14%), memory impairment (80%), personality disorders
      (31%), seizures (6%), psychosis (3%). Post-traumatic stress disorder (PTSD) is
      one of the most common and important disorders with lifetime PTSD (8-59%),
      current PTSD (2-33%) and the QOL in chemical warfare victims decreased.
      CONCLUSION: Exposure to chemical weapons may lead to physical, mental, social,
      and economic damages and consequently decrease the victims' (QOL. Therefore, they
      should be taken into more care.

PMID- 25780371
TI  - Impact of psychological violence on pregnancy outcomes in a prospective study.
AB  - OBJECTIVE: Violence during pregnancy has been associated with adverse pregnancy
      outcomes. This study aimed to explore the link between psychological violence
      (PSV) and pregnancy outcomes in terms of maternal and birth for the first time in
      women attending Mazandaran University of Medical Sciences (MUMS) primary health
      centers (PHCs) in Iran. METHODS: Prospective cohort of 1461 pregnant women
      exposed and non-exposed to PSV was followed until the pregnancy outcome. Modified
      Intimate Partner Violence, demographic and pregnancy outcomes questionnaires were
      administered face-to-face. Logistic regression analysis was down to estimate
      independent effects of the PSV on pregnancy outcomes. RESULTS: More than half of
      the women (69.9%) reported PSV during pregnancy. The differences between the two
      groups in reference with pregnancy complication did not reach statistical
      significance. Premature rapture of membrane was the only outcome that was
      independently associated with PSV. CONCLUSION: PSV in pregnancy was frequent in
      our study. Although the lack of adverse pregnancy outcome following PSV was
      observed in this study, intervention is required to prevent the effect of
      violence on women and child health.

PMID- 25780372
TI  - Comparison of Temperament and Character in Major Depressive Disorder Versus
      Bipolar II Disorder.
AB  - OBJECTIVE: The aim was to determine how personality of major depressive disorder
      (MDD) patients is different from that of bipolar II disorder (BIID) patients.
      METHODS: In this cross-sectional study, two groups of patients with MDD (47
      patients) and BIID (45 patients) between 18 and 55 years old were included and
      compared. The research instrument that subjects answered to was Temperament and
      Characteristic Inventory-125-R. RESULTS: Among temperament dimensions, novelty
      seeking, and reward-dependently in contrast with other traits such as harm
      avoidance and persistence showed a significant difference between the two studied
      groups. Among characteristic dimensions, self-direction and self-transcendence
      demonstrated a significant difference between the two groups (p < 0.005).
      CONCLUSION: Patients suffering from BIID are sensation seeker and are motivated
      by stimulates more often than MDD patients are. They feel euphoria more and, find
      the world more stimulating.

PMID- 25780373
TI  - A comparative study of thought fusion beliefs and thought control strategies in
      patient with obsessive-compulsive disorder, major depressive disorder and normal
      people.
AB  - OBJECTIVE: The present study aimed to investigate the metacognitive model of
      obsessive-compulsive disorder (OCD), through a comparative study of thought
      fusion beliefs and thought control strategies between patients with OCD,
      depression, and normal people. METHODS: This is a causal-comparative study. About
      20 patients were selected with OCD, and 20 patients with major depression
      disorder (MDD), and 20 normal individuals. Participants completed a thought
      fusion instrument and thought control questionnaire. Data were analyzed using
      multivariate analysis of variance. RESULTS: RESULTS indicated that patients with
      OCD obtained higher scores than two other groups. Also, there was a statistical
      significant difference between the three groups in thought control strategies and
      punishment, worry, and distraction subscales. CONCLUSION: Therefore, the results
      of the present study supported the metacognitive model of obsessive and showed
      thought fusion beliefs and thought control strategies can be effective in onset
      and continuity of OCD.

PMID- 25780374
TI  - Relationships between self-efficacy, self-esteem and procrastination in
      undergraduate psychology students.
AB  - OBJECTIVE: The present study aimed to review the relationships between
      procrastination and two self-factors self-efficacy and self-esteem. METHODS:
      Participants were 140 undergraduates Psychology students enrolled in Mohagheg
      Ardabili University, Ardabil, Iran. Instruments used for collecting the required
      data were the student-version of the General Procrastination Scale (GP-S),
      General Self-Efficacy Scale (GSE) and Rosenberg's Self-Esteem Scale (SES).
      RESULTS: Using causal modeling, two models were compared; a model with self
      esteem as a mediator versus a model with procrastination as a mediator. The self
      esteem mediator model accounted for 21% of the variance in procrastination. The
      significance of the mediation effect was found by bootstrapping method.
      CONCLUSION: The relationship of procrastination with self-esteem and self
      efficacy was revealed among undergraduate psychology students.

PMID- 25780375
TI  - The effect of self-disclosure skill training on communication patterns of
      referred couples to counseling clinics.
AB  - OBJECTIVE: This study aimed to examine the effect of self-disclosure skill
      training on communication patterns of referred couples to counseling clinics in
      Bandar Abbas. METHODS: The applied research design was an experimental study
      using pre-test and post-test, which was performed on a population of all referred
      couples to counseling clinics in Bandar Abbas who were interested to participate
      in a self-disclosure training workshop in response to the announcement. This
      study was performed on 26 couples who were selected by simple, convenient
      sampling method; however, they were randomly assigned to the control and
      experiment groups. A pre-test was administrated before self-disclosure training.
      The applied instrument includes Christensen and Salavy's scale of communication
      patterns. Participants in the experiment group had six sessions of training
      workshop, each lasted for 90 min. After the intervention, both groups answered
      the questionnaire again. The collected data were analyzed with paired t-test and
      covariance statistics. RESULTS: The results showed that the intervention led to
      significant (p < 0.05) increase in mutual constructive communication pattern and
      a reduction in mutual avoidance, demand/withdraw, demanding man/withdrawing woman
      communication patterns. It was also found that the training was not effective on
      the communication pattern of demanding woman/withdrawing man. CONCLUSION: The
      training of simple, but important skills of self-disclosure can help couples to
      improve their communication and consequently improve their marital satisfaction.

PMID- 25780376
TI  - Spiritual Development and Death Attitude in Female Patients With Type II
      Diabetes.
AB  - OBJECTIVE: The present study aimed to investigate the differences regarding
      spiritual development dimensions and death attitude profiles, and also to
      determinate association between them, in patients suffering from type II
      diabetes. METHODS: In a cross-sectional design study, 100 female outpatients who
      were suffering from type II diabetes were recruited in Imam Khomeini Hospital,
      Sari, Iran. Data were collected through two questionnaires including the
      Spiritual Assessment Inventory (SAI) and the Death Attitude Profile-Revised
      (DAPR). Analysis of the data involved analysis of covariance (ANCOVA) with the
      Fisher's Least Significant Difference (LSD) as post-hoc test plus the Pearson
      correlation. RESULTS: There was a statistical significant difference in spiritual
      development dimensions and death attitude profile. The results showed that
      spiritual development were significantly associated with some items of death
      attitude profiles. CONCLUSION: Awareness of God was suitable in diabetic
      patients, but the quality of relationship with God indicated spiritually
      immature. It is necessary to provide instruction to improve patient's death
      attitude and following health behavior.

PMID- 25780377
TI  - Relationship between perceived social self-efficacy and depression in
      adolescents.
AB  - OBJECTIVE: The objective of the present study is to investigate the relationship
      of perceived social self-efficacy (PSSE) with depression in students. METHODS:
      The sample of the present study consisted of 216 adolescent students including
      120 males and 96 females randomly selected from different educational institutes
      of Karachi, Pakistan. The age of the participants ranged from 16 to 19 years old,
      with the mean age of 17.09 +/- 1.13 years. Personal information form, PSSE scale,
      and Siddiqui-Shah depression scale were administered on the adolescent students
      to check the following hypothesis; there would be a negative correlation between
      PSSE and depression in adolescents. RESULTS: Pearson product moment coefficient
      of correlation was applied to analyze the relationship between PSSE and level of
      depression in adolescent students. Findings of the study showed a significant
      negative correlation (r = -0.149, p < 0.05) between the variables of PSSE and
      depression. CONCLUSION: There is a relationship between PSSE and depression in
      adolescents.

PMID- 25780378
TI  - Effect of reminiscence on cognitive status and memory of the elderly people.
AB  - OBJECTIVE: The present study aimed to determine the effect of reminiscence on
      cognitive status and memory of a sample of elderly people who lived in aged day
      centers in Golestan province, Iran. METHODS: This study was a semi-experimental
      research. The subjects consisted of 45 elderly people who referred to the aged
      day centers of Golestan province. Each four groups of 45 aged subjects (4 groups
      of 10-12 subjects) took part in 8 reminiscence sessions which lasted one to one
      and half hour. Cognitive status and of the aged, before and after taking part,
      was assessed by Mini Mental State Examination and Wechsler Memory Scale. RESULTS:
      Mean (+/-SD) cognitive status score at pre-test stage was 24 (+/-2) which
      increased to 25 (+/-2) at post-test stage (p < 0.01). Mean (+/-SD) intelligence
      quotient was 87 (+/-7) at pre-test stage which increased to 92 (+/-10) at post
      test stage (p < 0.01). CONCLUSION: Reminiscence sessions held for the aged
      studied here had beneficial effects on cognition and memory of the subjects.

PMID- 25780379
TI  - Sertraline-related bleeding tendency: could it be dose-dependent?
AB  - Selective serotonin reuptake inhibitors (SSRIs) are reported to be associated
      with increased bleeding tendency. While findings of recent studies explain a lot
      about the pathophysiology of this side-effect, there is a general tendency to
      discontinue SSRIs as harmful medications. We report two instances of dose
      dependent relations between sertraline and bleeding tendency. Bleeding diathesis
      was alleviated by adjusting dosage of medication. It could be argued that
      benefits of SSRIs could outweigh this potential and probably avoidable side
      effect; if dose-adjustment is properly implemented. 

PMID- 25780380
TI  - The relationship between religious orientation, and gender with a cognitive
      distortion.
AB  - OBJECTIVE: The objective of this study was to determine the relationship between
      religious orientation (intrinsic-external) and cognitive distortions. METHODS:
      General design of this study considered as a descriptive and correlational
      method. Universal population in this research consist all students of the Urmia
      Azad University, which were studying during 2012 and 2013 (n = 250). All
      respondents filled the Alports religious and cognitive distortions
      questionnaires. The answers were analyzed with step by step regression and
      correlation method. RESULTS: The research showed a significant relationship
      between the religious orientation and cognitive distortions (p < 0.005) (p <
      0.001). CONCLUSION: The results suggest that religious orientation is an
      important factor in cognitive distortions and individuals with intrinsic
      religious orientation have less cognitive distortion.

PMID- 25780381
TI  - Recommendations for research studies on treatment of idiopathic scoliosis:
      Consensus 2014 between SOSORT and SRS non-operative management committee.
AB  - The two main societies clinically dealing with idiopathic scoliosis are the
      Scoliosis Research Society (SRS), founded in 1966, and the international Society
      on Scoliosis Orthopedic and Rehabilitation Treatment (SOSORT), started in 2004.
      Inside the SRS, the Non-Operative Management Committee (SRS-NOC) has the same
      clinical interest of SOSORT, that is the Orthopaedic and Rehabilitation (or Non
      Operative, or conservative) Management of idiopathic scoliosis patients. The aim
      of this paper is to present the results of a Consensus among the best experts of
      non-operative treatment of Idiopathic Scoliosis, as represented by SOSORT and
      SRS, on the recommendation for research studies on treatment of Idiopathic
      Scoliosis. The goal of the consensus statement is to establish a framework for
      research with clearly delineated inclusion criteria, methodologies, and outcome
      measures so that future meta- analysis or comparative studies could occur. A
      Delphi method was used to generate a consensus to develop a set of
      recommendations for clinical studies on treatment of Idiopathic Scoliosis. It
      included the development of a reference scheme, which was judged during two
      Delphi Rounds; after this first phase, it was decided to develop the
      recommendations and 4 other Delphi Rounds followed. The process finished with a
      Consensus Meeting, that was held during the SOSORT Meeting in Wiesbaden, 8-10 May
      2014, moderated by the Presidents of SOSORT (JP O'Brien) and SRS (SD Glassman)
      and by the Chairs of the involved Committees (SOSORT Consensus Committee: S
      Negrini; SRS Non-Operative Committee: MT Hresko). The Boards of the SRS and
      SOSORT formally accepted the final recommendations. The 18 Recommendations
      focused: Research needs (3), Clinically significant outcomes (4), Radiographic
      outcomes (3), Other key outcomes (Quality of Life, adherence to treatment) (2),
      Standardization of methods of non-operative research (6). 

PMID- 25780382
TI  - Analysis of hydrazine in smokeless tobacco products by gas chromatography-mass
      spectrometry.
AB  - BACKGROUND: Due to the lower health risks associated with the use of certain
      categories of smokeless tobacco products (STPs) such as Swedish snus, there is
      interest in the comparative levels of toxic chemical constituents in different
      types of STPs. A method has been developed and validated for the analysis of
      hydrazine in STPs. Seventy four commercial STPs from the US and Sweden,
      representing 80-90% of the 2010 market share for all the major STP categories in
      these two countries, as well as three reference STPs, were analysed for
      hydrazine. RESULTS: Aqueous extracts of the STPs were treated with excess
      pentafluorobenzaldehyde (PFB), which reacted with hydrazine in solution to form
      decafluorobenzaldehyde azine (DFBA). DFBA was partitioned into hexane and then
      quantified by gas chromatography-mass spectrometry (GC-MS). The method was
      validated using five different types of STP, was linear in the range 8-170 ng/mL,
      and had limits of quantification (LOQ) from 26-53 ng of hydrazine per g of STP
      (as sold). The method was applied to the analysis of 74 contemporary STPs
      commercially available in the United States and Sweden, none of which were found
      to contain hydrazine above the LOQ or LOD. Trace levels of compounds showing
      chromatographic and mass spectral features consistent with hydrazine were
      identified at very low levels (sub-limit of detection, <10 ng/g) in the
      chromatograms of less than half of the 74 STPs examined; in contrast, for 40 of
      the STPs no evidence for the presence of hydrazine was observed. Where present,
      the levels of compounds consistent with hydrazine were estimated to be at least
      an order of magnitude lower than the only previous study to have quantified
      hydrazine in tobacco. CONCLUSIONS: Our results show that hydrazine is not a
      prevalent constituent of STPs, and when present is not quantifiable using
      currently available analytical methodology.

PMID- 25780383
TI  - Distribution and treatment of clavicular fractures in monotrauma and polytrauma
      patients.
AB  - BACKGROUND: Although extensive research for the optimal treatment of clavicle
      fractures has been performed, comparative studies between monotrauma and
      polytrauma patients are lacking. OBJECTIVE: To compare fracture distribution and
      treatment in monotrauma and polytrauma patients with a clavicle fracture.
      METHODS: Single center retrospective cohort study. Fractures were classified by
      the Robinson classification. Monotrauma patients sustained only a clavicle
      fracture or a clavicle fracture plus a minor abrasion, hematoma, or superficial
      skin lesion leading to an Injury Severity Score (ISS) of 4 or 5 respectively.
      Polytrauma patients had an ISS >=16 as a result of injury in 2 or more
      Abbreviated Injury Scale (AIS) regions. RESULTS: 154 monotrauma and 155
      polytrauma patients with a clavicle fracture were identified. Monotrauma patients
      had a higher incidence of Type IIB fractures (displaced midshaft) compared to
      polytrauma patients (P = 0.002). No difference was observed regarding Type I
      (medial) and Type III (lateral) fractures. In monotrauma patients, Type IIB
      fractures were treated operatively more frequently (P = 0.004). The initial
      treatment for Type I and Type III fractures did not differ between monotrauma and
      polytrauma patients. CONCLUSIONS: Monotrauma patients had a higher incidence of
      displaced midshaft clavicle fractures compared to polytrauma patients, and
      monotrauma patients with displaced midshaft clavicle fractures were treated
      operatively more frequently. No differences were found in the distribution and
      treatment of medial and lateral clavicle fractures.

PMID- 25780384
TI  - Hepatic pseudoaneurysm after traumatic liver injury; is CT follow-up warranted?
AB  - INTRODUCTION: Hepatic pseudoaneurysm (HPA) is a rare complication after liver
      trauma, yet it is potentially fatal, as it can lead to sudden severe haemorrhage.
      The risk of developing posttraumatic HPA is one of the arguments for performing
      follow-up CT of patients with liver injuries. The aim of this study was to
      investigate the occurrence of HPA post liver trauma. METHODS: A retrospective
      study from 2000-2010 of conservatively treated patients with blunt liver trauma
      was performed to investigate the incidence and nature of HPA. After the initial
      CT scan patients were admitted to the department and if not clinically indicated
      prior a follow-up CT was performed on day 4-5. RESULTS: A total of 259 non
      operatively managed patients with liver injury were reviewed. 188 had a follow-up
      CT or US and in 7 patients a HPA was diagnosed. All aneurysms were treated with
      angiographic embolization and there were no treatment failures. There was no
      correlation between the severity of the liver injury and development of HPA. 5
      out of 7 patients were asymptomatic and would have been discharged without
      treatment if the protocol did not include a default follow-up CT. CONCLUSIONS: In
      conclusion, this study shows that HPA is not correlated to the severity of liver
      injury and it develops in 4% of patients after traumatic liver injury. In order
      to avoid potentially life-threatening haemorrhage from a post trauma hepatic
      pseudoaneurysm, it seems appropriate to do follow-up CT as part of the
      conservative management of blunt and penetrating liver injuries.

PMID- 25780385
TI  - An overview of the mental health system in Gaza: an assessment using the World
      Health Organization's Assessment Instrument for Mental Health Systems (WHO-AIMS).
AB  - BACKGROUND: Mental health system reform is urgently needed in Gaza to respond to
      increasing mental health consequences of conflict. Evidence from mental health
      systems research is needed to inform decision-making. We aimed to provide new
      knowledge on current mental health policy and legislation, and services and
      resource use, in Gaza to identify quality gaps and areas for urgent intervention.
      METHODS: As part of a mixed methods study, we used the World Health
      Organization's Assessment Instrument for Mental Health Systems Version 2.2 to
      collect data on mental health services and resources. Data collection was carried
      out in 2011, based on the year 2010. RESULTS: Gaza's mental health policy
      suggests some positive steps toward reform such as supporting
      deinstitutionalisation of mental health services. The decrease in the number of
      beds in the psychiatric hospital and the progressive transition of mental
      healthcare toward more community based care are indicative of
      deinstitutionalisation. However, mental health legislation in support of
      deinstitutionalisation in Gaza is lacking. The integration of mental health into
      primary healthcare and general hospitals has not been fully achieved. Mental
      health in Gaza is underfunded, human rights protection of service users is
      absent, and human resources, service user advocacy, and mental health training
      are limited. CONCLUSION: Priority needs to be given to human rights protection,
      mental health training, and investment in human and organisational resources.
      Legislation is needed to support policy and plan development. The ongoing
      political conflict and expected increase in need for mental health services
      demonstrates an urgent response is necessary.

PMID- 25780386
TI  - Length of stay of psychiatric admissions in a general hospital in Ethiopia: a
      retrospective study.
AB  - BACKGROUND: In sub-Saharan Africa, the number of psychiatric beds per population
      is disproportionately low. Moreover, there is a lack of data regarding the
      patterns of psychiatric admissions and the factors leading to long psychiatric
      hospitalization in this region. This study aimed to investigate the average
      length of stay (LOS) and the factors associated with prolonged hospitalizations.
      METHODS: A ten-year retrospective chart review of patients admitted to the
      psychiatric facility of Jimma University Specialized Hospital in southwest
      Ethiopia was conducted. The medical charts of 846 admissions spanning the period
      from January 2001 to December 2010 were reviewed. LOS greater than 21 days was
      considered as a cut-off point for lengthier stay. Bivariate and multivariable
      logistic regression analyses were conducted to identify factors independently
      associated with LOS. RESULTS: The most common discharge diagnoses were
      schizophrenia and other psychotic disorders (27.6%), and bipolar disorder
      (23.4%). A global clinical rating taken on discharge showed 90.3% improved
      outcome. The median (25th, 75th percentiles) LOS was 22 (15, 36) days. Patients
      with major depressive disorder [aOR = 0.51 (0.32 - 0.81)] and brief psychotic
      disorder [aOR = 0.52 (0.33 - 0.84)] were less likely than patients with
      schizophrenia and other psychotic disorders to have long hospital stays. Presence
      of extrapyramidal side-effects and out of pocket expenditures predicted LOS.
      CONCLUSIONS: Patients with psychoses and bipolar disorder have lengthier hospital
      stays burdening the cost of care of psychiatric treatment in a general hospital
      setting. Our findings call for identifying those cases quickly, attending to
      their needs with evidence-based efficient treatment and for improving and
      developing an aftercare system such that the utilization of acute inpatient beds,
      already a scarce resource, could achieve higher efficiency.

PMID- 25780387
TI  - Development of mental health problems - a follow-up study of unaccompanied
      refugee minors.
AB  - BACKGROUND: Studies have shown that unaccompanied refugee children have elevated
      symptoms of post-traumatic stress disorder (PTSD), depression, anxiety, and
      externalizing problems. Few studies have examined change in this group's mental
      health symptoms after resettlement in a new country, particularly for those who
      arrive to a host country when being under the age of 15. METHOD: The sample
      included 75 unaccompanied refugee children (mean age 16.5 years, SD =1.6; 83%
      boys) who settled in Norway. We examined change in the number of stressful life
      events, symptoms of PTSD (Child PTSD Symptom Scale; CPSS), and symptoms of
      anxiety, depression and externalizing problems (Hopkins Symptom Checklist; HSCL
      37A) from 6 months after arrival (T1) to 1.9 years (SD =0.6) later (T2) using
      paired samples t-tests. Linear regression models were used to examine whether
      length of stay, level of education or change in the number of experienced
      stressful life events predicted symptom change. RESULTS: There was a small and
      non-significant change in the mean scores of both symptom scales between T1 and
      T2, although there was considerable variation among the participants. The number
      of children who remained above the clinical cut-off value from T1 to T2 was as
      follows: 28 of 47 (59.6%) on the CPSS and eight of 16 (50.0%) on the HSCL-37A.
      There was a significant increase in the number of reported stressful life events
      from T1 to T2. An increase in reported stressful life events predicted an
      increase in PTSS (beta =1.481, 95% CI .552 to 2.411). Length of stay, increase in
      stressful life events and level of education did not predict changes in the HSCL
      37A. CONCLUSIONS: There was no average change in the level of PTSS, depression,
      anxiety, or externalizing problems in this group of unaccompanied refugee
      children from shortly after arrival to nearly two years later. The large
      variation in change scores across informants indicates a need for monitoring the
      development of mental health problems and securing that the youth's primary
      psychosocial needs are met. The high rate of children above clinical cut-off on
      the symptoms scales and with suicidal ideation indicates that many may be in need
      of treatment.

PMID- 25780388
TI  - O brave new world that has such machines in it.

PMID- 25780389
TI  - Thyroid function is associated with insulin resistance markers in healthy
      adolescents with risk factors to develop diabetes.
AB  - INTRODUCTION: The prevalence of obesity and Type 2 diabetes mellitus (T2DM) among
      children and adolescents is rising. Thyroid function has been associated with
      insulin resistance. There is scarce information about how thyroid function could
      be related with cardiovascular risk or glucose homeostasis in adolescent. AIM: To
      analyze how thyroid function is associated with insulin resistance and another
      cardiovascular risk factors in healthy adolescents with risk factors to develop
      diabetes. METHODS: A prospective cross-sectional analysis was carried out on
      euthyroid, adolescents. considered at high risk to develop Type 2 diabetes.
      Fasting blood samples were obtained. Thyroid function test and another
      cardiometabolic parameters were assessed. A 75 grams oral glucose tolerance test
      was performed to calculate insulin resistance. RESULTS: One hundred adolescents
      were evaluated. The mean age was 15.9 +/- 0.8 years, There is a negative
      correlation between Fasting insulin, post glucose load insulin and HOMA IR. There
      were no correlation with Matsuda index. We could not found any correlation with
      TSH values. CONCLUSIONS: We found a correlation between fasting insulin, HOMA IR
      and serum thyroid hormones, we did not find any relation with serum TSH. In
      euthyroid adolescents with risk factors to develop diabetes.

PMID- 25780390
TI  - Changes in the neurochemistry of athletes with repetitive brain trauma:
      preliminary results using localized correlated spectroscopy.
AB  - INTRODUCTION: The goal was to identify which neurochemicals differ in
      professional athletes with repetitive brain trauma (RBT) when compared to healthy
      controls using a relatively new technology, in vivo Localized COrrelated
      SpectroscopY (L-COSY). METHODS: To achieve this, L-COSY was used to examine five
      former professional male athletes with 11 to 28 years of exposure to contact
      sports. Each athlete who had had multiple symptomatic concussions and repetitive
      sub concussive trauma during their career was assessed by an experienced
      neuropsychologist. All athletes had clinical symptoms including headaches, memory
      loss, confusion, impaired judgment, impulse control problems, aggression, and
      depression. Five healthy men, age and weight matched to the athlete cohort and
      with no history of brain trauma, were recruited as controls. Data were collected
      from the posterior cingulate gyrus using a 3 T clinical magnetic resonance
      scanner equipped with a 32 channel head coil. RESULTS: The variation of the
      method was calculated by repeated examination of a healthy control and phantom
      and found to be 10% and 5%, respectively, or less. The L-COSY measured large and
      statistically significant differences (P <=0.05), between healthy controls and
      those athletes with RBT. Men with RBT showed higher levels of glutamine/glutamate
      (31%), choline (65%), fucosylated molecules (60%) and phenylalanine (46%). The
      results were evaluated and the sample size of five found to achieve a
      significance level P = 0.05 and a power of 90%. Differences in N-acetyl aspartate
      and myo-inositol between RBT and controls were small and were not statistically
      significance. CONCLUSIONS: A study of a small cohort of professional athletes,
      with a history of RBT and symptoms of chronic traumatic encephalopathy when
      compared with healthy controls using 2D L-COSY, showed elevations in brain
      glutamate/glutamine and choline as recorded previously for early traumatic brain
      injury. For the first time increases in phenylalanine and fucose are recorded in
      the brains of athletes with RBT. Larger studies utilizing the L-COSY method may
      offer an in-life method of diagnosis and personalized approach for monitoring the
      acute effects of mild traumatic brain injury and the chronic effects of RBT.

PMID- 25780391
TI  - Kidney disease as a determinant of cognitive decline and dementia.
AB  - Chronic kidney disease (CKD) has evolved as a possible new determinant of
      cognitive decline and dementia. This review outlines the presumed pathophysiology
      of cognitive decline in CKD, which consists of traditional and new vascular risk
      factors as well as nonvascular risk factors and metabolic and biochemical
      abnormalities within the central nervous system caused by CKD. The recent major
      cross-sectional studies and longitudinal studies - including one meta-analysis -
      that mostly suggest an association of cognitive decline and CKD are discussed.
      Finally, potential therapeutic strategies are presented. 

PMID- 25780392
TI  - Role of the angiopoietin/Tie system in pregnancy (Review).
AB  - Angiopoietin-1 and -2 are endogenous ligands for the vascular endothelium
      specific receptor tyrosine kinase Tie-2. The angiopoietin/Tie system plays a
      critical role in the regulation of endothelial cell survival and vascular
      maturation and stability. Apart from its well-established role in vascular
      morphogenesis, emerging data support the involvement of angiopoietins in
      inflammation and various malignancies. Previous studies have underlined the
      significance of several angiogenic factors in normal placental development. In
      addition, angiogenic imbalance is observed in pregnancy complications related to
      impaired placentation, such as preeclampsia (PE) and intrauterine growth
      restriction (IUGR). However, there is only limited information available on the
      role of the angiopoietin/Tie system in the establishment of a competent feto
      maternal vascular system. In this review, we present the current knowledge
      regarding the role of angiopoietins in normal pregnancy and pregnancy
      complications.

PMID- 25780393
TI  - Quantitative analysis of factors influencing tissue-engineered bone formation by
      detecting the expression levels of alkaline phosphatase and bone gamma
      carboxyglutamate protein 2.
AB  - Bone tissue engineering is a promising alternative approach that permits the
      efficient reconstruction of bone defects. There are four elements involved in
      bone tissue engineering technology, including the seed cells, growth factors,
      scaffolds and culture environment. The aim of the present study was to evaluate
      the effect of these factors on bone formation in tissue engineering technology by
      analyzing the expression of osteogenetic markers using polymerase chain reaction
      (PCR). Bone marrow mesenchymal stem cells (BMSCs) were extracted from the bone
      marrow of the bilateral tibial platform of New Zealand white rabbits. In
      addition, platelet-rich plasma (PRP) samples were prepared from blood extracted
      from the ear vein of the rabbits. A perfusion bioreactor was used to provide the
      culture environment, and beta-tricalcium phosphate (beta-TCP) was used to build
      the scaffolds. The beta-TCP scaffolds were divided into five groups and each
      group was treated with a different combination of the factors. Next, the
      composites were implanted into the rabbits. After three months, the expression
      levels of the new bone formation markers, alkaline phosphatase and bone gamma
      carboxyglutamate protein 2, were detected using quantitative reverse
      transcription-PCR analysis. The expression levels of the markers in the
      experimental groups were higher compared with the negative control group.
      Comparisons between the experimental groups also revealed statistical
      significance. Scanning electron microscopy revealed good adhesion and
      distribution of the BMSCs on the beta-TCP scaffold. In conclusion, the PCR
      results indicated that PRP, BMSCs and the bioreactor exhibited a promoting effect
      on bone formation.

PMID- 25780394
TI  - Role of tissue transglutaminase in the pathogenesis of diabetic cardiomyopathy
      and the intervention effect of rutin.
AB  - The aim of this study was to investigate the role of tissue transglutaminase
      (tTG) in the pathogenesis of diabetic cardiomyopathy (DCM) and the intervention
      effect of rutin. DCM was induced in rats by the injection of streptozotocin (STZ;
      25 mg/kg). After a preliminary examination, the rats were randomly divided into
      four groups: Control (n=8), STZ-induced DCM (n=8), STZ + positive drug
      (captopril; n=6) and STZ + rutin (n=8) groups. The DCM model was evaluated using
      blood sugar values, serum enzyme levels, hematoxylin and eosin staining and
      Masson's staining, ex vivo. The protein and mRNA expression of tTG was assessed
      with immunohistochemistry, western blotting and reverse transcription
      quantitative polymerase chain reaction (RT-qPCR). The rat model of DCM was
      successfully established by STZ administration, and the expression levels of tTG
      were significantly increased in the DCM model. Following the injection of
      captopril or rutin, the blood sugar values, collagen content and expression
      levels of tTG were gradually reduced and serum enzyme levels were increased, as
      compared with those in the STZ-induced DCM group. In conclusion, tTG plays an
      important role in STZ-induced DCM. In addition, rutin may inhibit the expression
      of tTG and regulate myocardial injury in STZ-induced DCM.

PMID- 25780395
TI  - Blastic plasmacytoid dendritic cell neoplasm with leukemic manifestation and ETV6
      gene rearrangement: A case report.
AB  - Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare malignant tumor of
      the hemopoietic system that arises from plasmacytoid dendritic cell precursors
      with a highly aggressive course. BPDCN frequently involves the skin, lymph nodes,
      peripheral blood and bone marrow. BPDCN is known to develop leukemic
      dissemination as a feature of myelomonocytic leukemia in the late phase of the
      disease, which leads to a poorer prognosis. In the present study, a case of BPDCN
      with leukemic manifestation without cutaneous involvement was reported. In
      addition, ETS variant gene 6 (ETV6) gene rearrangement was detected in the
      patient. The patient relapsed soon after complete remisson and had no response to
      further treatment. To the best of our knowledge, this is the first reported case
      of BPDCN with ETV6 rearrangement. Following chemotherapy treatment, the patient
      suffered from severe headache in the complete remission stage; however, brain CT
      scans showed no significant abnormalities. Several lumbar punctures and
      intrathecal chemotherapy were performed, and the patient recovered gradually.
      Therefore, the patient was considered to suffer from central nervous system
      leukemia. In conclusion, implementation of lumbar punctures and preventive
      intrathecal chemotherapy are required in BPDCN patients with leukemic
      manifestation during the remission stage.

PMID- 25780396
TI  - Accuracy of computer-aided geometric three-dimensional reconstruction of the
      human petrous bone based on serial unstained celloidin sections.
AB  - The aim of this study was to present a comprehensive three-dimensional (3D)
      morphology of the petrous bone with computer image-processing technology, which
      could be beneficial for the teaching of anatomy and for surgical procedures. The
      unstained celloidin sections of human temporal bone were digitized with high
      resolution and quality, and then processed with Amira(r) software to include
      alignment, segmentation and reconstruction. The integral structure of the human
      inner ear was presented with computer modeling, including the petrous bone, bone
      labyrinth, internal carotid artery canal, internal jugular vein canal, sigmoid
      sinus, inferior petrosal sinus, glossopharyngeal meatus, vagal meatus, internal
      acoustic meatus, facial nerve canal, greater superficial petrosal nerve,
      vestibular aqueduct, extraosseous portion of the endolymphatic sac, round and
      oval window, processus cochleariformis and pyramidal eminence. The 3D model
      showed detailed structure of the external and internal petrous bone, as well as
      their spatial relationship. The present study suggests the feasibility of
      comprehensive 3D reconstruction of the petrous bone using unstained celloidin
      sections, which may provide advantages for future study.

PMID- 25780398
TI  - microRNA-23b regulates the expression of inflammatory factors in vascular
      endothelial cells during sepsis.
AB  - miR-23b is a multifunctional microRNA that contributes to the regulation of
      multiple signaling pathways. It has been reported that miR-23b prevents multiple
      autoimmune diseases through the regulation of inflammatory cytokine pathways. In
      addition, the function and underlying mechanisms of miR-23b on sepsis are
      currently being investigated. In the present study, miR-23b inhibitor and mimics
      sequences were transfected into human vascular endothelial cells to inhibit and
      upregulate the expression of miR-23b, respectively. In addition, respective
      negative control (NC) sequences were transfected. The expression of miR-23b was
      found to be downregulated in the cells transfected with the mimics NC or
      inhibitor NC sequences following stimulation with lipopolysaccharide (LPS;
      P<0.01); however, higher expression levels were maintained in the cells
      transfected with the mimics sequence and very low levels were observed in the
      cells transfected with the inhibitor sequence. In addition, the expression levels
      of nuclear factor (NF)-kappaB, tumor necrosis factor (TNF)-alpha, interleukin
      (IL)-6, intercellular adhesion molecule (ICAM)-1, E-selectin and vascular cell
      adhesion molecule (VCAM)-1 were shown to increase following induction by LPS in
      the cells transfected with inhibitor/mimics NC sequences (P<0.05). However, the
      expression levels of these inflammatory factors decreased in the cells
      transfected with the mimics sequence, and increased to a greater degree in the
      cells transfected with the inhibitor sequence, as compared with the inhibitor NC
      sequences (P<0.05). Therefore, miR-23b may play a significant role in the
      pathogenesis and progression of sepsis by inhibiting the expression of
      inflammatory factors, including NF-kappaB, TNF-alpha, IL-6, ICAM-1, E-selectin
      and VCAM-1.

PMID- 25780399
TI  - Protective effect of Lai Fu Cheng Qi decoction on severe acute pancreatitis
      induced myocardial injury in a rat model.
AB  - The aim of the present study was to evaluate the effects of Lai Fu Cheng Qi
      decoction on myocardial injury in rats with severe acute pancreatitis (SAP). In
      total, 30 rats were randomly divided into sham, SAP and decoction treatment
      groups. SAP was induced by a retrograde pancreatic duct injection of 5% sodium
      taurocholate in the SAP and decoction treatment groups. Rats in decoction
      treatment group also received intragastric administration of Lai Fu Cheng Qi
      decoction. The serum levels of creatine kinase isoenzyme (CK-MB) and lactate
      dehydrogenase (LDH) were detected using an automatic biochemical analyzer. In
      addition, myocardial Na+-K+-ATPase activity was analyzed using a
      spectrophotometric method and the mitochondrial membrane potential was measured
      by flow cytometry. Myocardial apoptosis was assessed using a TUNEL assay and
      pathological changes to the heart and pancreas were detected by hematoxylin and
      eosin staining. Compared with the rats in the sham group, rats in the SAP and
      decoction treatment groups exhibited significantly higher levels of serum CK-MB
      and LDH, apoptosis index and pathological scores, and had significantly lower
      levels of Na+-K+-ATPase activity and mitochondrial membrane potential. However,
      when compared with the SAP group, the serum levels of CK-MB and LDH, the
      pathological scores of the pancreas and heart, and the myocardial cell apoptosis
      index in the decoction treatment group were significantly lower. Furthermore, the
      Na+-K+-ATPase activity and mitochondrial membrane potential were significantly
      increased in the decoction treatment group when compared with the SAP group.
      Therefore, Lai Fu Cheng Qi decoction was shown to exert a protective effect on
      myocardial injury induced by SAP in rats.

PMID- 25780397
TI  - Extravasated platelet aggregation in liver zone 3 may correlate with the
      progression of sinusoidal obstruction syndrome following living donor liver
      transplantation: A case report.
AB  - Sinusoidal obstruction syndrome (SOS), previously known as veno-occlusive
      disease, is relatively rare subsequent to liver transplantation (LT). SOS
      refractory to medical therapy, however, can result in centrilobular fibrosis,
      portal hypertension and liver failure. Although sinusoidal endothelial cell
      damage around central venules (zone 3) occurs early in the development of SOS,
      the detailed mechanism of SOS development and its association with
      thrombocytopenia are not yet completely understood. The present report describes
      a patient who experienced SOS with unexplained thrombocytopenia following living
      donor LT. The progression of SOS resulted in graft dysfunction and the patient
      succumbed. The presence of platelets in the liver allograft was assayed
      immunohistochemically using antibody to the platelet marker cluster of
      differentiation 42b (platelet glycoprotein Ib). Platelet aggregates were found
      attached to hepatocytes along the sinusoid and within the cytoplasm of
      hepatocytes, particularly in zone 3. By contrast, no staining was observed in
      zone 1. These findings suggested that extravasated platelet aggregation in the
      space of Disse and the phagocytosis of platelets by hepatocytes were initiated by
      sinusoidal endothelial cell damage due to the toxicity of the immunosuppressant
      tacrolimus or a corticosteroid pulse, and that platelet activation and
      degranulation may be at least partially involved in the mechanism responsible for
      SOS.

PMID- 25780400
TI  - Synergistic effects of Buyang Huanwu decoction and embryonic neural stem cell
      transplantation on the recovery of neurological function in a rat model of spinal
      cord injury.
AB  - The aim of the present study was to investigate the therapeutic effect of a
      combined treatment of Buyang Huanwu decoction (BYHWD), a well-known formula of
      traditional Chinese medicine, and neural stem cells (NSCs) on spinal cord injury
      (SCI) and the associated underlying mechanisms. A SCI model was established by
      surgery via a complete transection of the T10 vertebra of female Sprague-Dawley
      rats. Gelatin sponges were used to absorb NSCs labeled with the thymidine analog,
      5-bromo-2-deoxyuridine (BrdU), and were transferred into the transected spinal
      cords. BYHWD was administered once a day by introgastric infusion. Motor
      functions of the hind limbs were evaluated using the 21-point locomotor rating
      scale developed by Basso, Beattie and Bresnahan (BBB). The fate of the
      transplanted NSCs under the various conditions was examined by double
      immunofluorescence staining, using markers for neurons, astrocytes and
      oligodendrocytes, with BrdU. Ultrastructural changes of the SCI site following
      the various treatments were examined under a transmission electron microscope.
      The number of double positive cells for glial fibrillary acidic protein and BrdU
      in the BYHWD + NSC group was significantly decreased when compared with that in
      the NSC group (P<0.05). However, the number of cells that were labeled double
      positive for myelin basic protein and BrdU, as well as neuron specific enolase
      and BrdU, was greater in the BYHWD + NSC group when compared with the NSC group.
      Electron microscopy demonstrated that treatment with BYHWD combined with NSCs
      significantly alleviated demyelination. Results from the BBB motor function test
      exhibited a significant improvement in the BYHWD + NSC group when compared with
      the SCI, BYHWD and NSC only groups. In conclusion, the results demonstrated that
      the traditional Chinese medicine formula, BYHWD, exerted an effect on the
      differentiation and migration of NSCs. Combining the administration of BYHWD with
      NSCs was shown to have a synergistic effect on the recovery of neurological
      function, mitigating the progress of demyelination or ameliorating the recovery
      of myelination.

PMID- 25780401
TI  - Application of renal-rotation techniques in retroperitoneoscopic partial
      nephrectomy.
AB  - Retroperitoneoscopic partial nephrectomy (RPN) is one of the standard methods for
      treating T1-stage renal carcinoma, which has a narrow operational space and a
      difficult surgical procedure. The aim of this study was to examine the safety and
      feasibility of renal-rotation techniques in RPN. Between April 2012 and June
      2014, the renal-rotation technique in RPN was performed in 22 male and 16 female
      patients, aged between 31 and 75 years (mean, 52 years), with stage T1N0M0 renal
      cell carcinoma. In 29 cases the tumor was located at the ventral side of the
      kidney, including 22 cases at the renal hilum, and in nine cases the tumor was
      located at the inferior pole of the kidney. The tumor size was between 1.5 and
      4.6 cm (mean, 2.8 cm). The results showed that, in all 38 cases, the procedure
      was successfully accomplished without conversion to open surgery. There were no
      intraoperative complications and only three cases of postoperative complications.
      The surgery duration was between 45 and 116 min (mean, 59 min); blood loss was
      between 10 and 120 ml (mean, 40 ml) and no patients required a blood transfusion.
      The average kidney ischemia time was 21 min (range, 15-38 min). No patients had
      local recurrence or metastasis after follow-up of between one and 26 months. In
      conclusion, the application of the renal-rotation technique in RPN for tumors
      located at the ventral side, renal hilum or at the inferior pole of the kidney is
      safe and feasible and worth wider clinical application.

PMID- 25780402
TI  - Seawater immersion aggravates sciatic nerve injury in rats.
AB  - The aim of the present study was investigate the impact of seawater immersion on
      peripheral nerve injury and the underlying mechanisms. A total of 234 specific
      pathogen-free Sprague-Dawley male rats were randomly divided into a sham group,
      injury control group and seawater immersion + injury group. The Sciatic
      Functional Index (SFI) was used to assess nerve function for 6 weeks after
      injury. Compound muscle action potentials were measured and hematoxylin and eosin
      (H&E) staining of nerve specimens was carried out at week 6. Levels of reactive
      oxygen species (ROS) and malondialdehyde (MDA) in nerve tissues were measured by
      enzyme-linked immunosorbent assay (ELISA), and the expression levels of inducible
      nitric oxide synthase (iNOS) mRNA and protein were measured by reverse
      transcription-quantitative polymerase chain reaction and immunohistochemistry,
      respectively. The SFI value in the seawater immersion + injury group after 6
      weeks was lower than that in the injury control group (P<0.05). The compound
      muscle action potential in the seawater immersion + injury group had a prolonged
      latency, and the amplitude and nerve conduction velocity were decreased compared
      with those in the other groups (P<0.05). H&E staining demonstrated that nerve
      fiber regeneration was worse in the seawater immersion + injury group. The ROS
      and MDA levels in the seawater immersion + injury group were higher than those in
      the other groups (P<0.05). The expression levels of iNOS mRNA and protein
      gradually increased in the injury and seawater immersion + injury groups and
      peaked at 48 h after surgery. Immersion in seawater further aggravated sciatic
      nerve injury and led to worse neuronal recovery. The mechanism may be associated
      with oxidative stress.

PMID- 25780403
TI  - Genetic stability of a recombinant adenovirus vaccine vector seed library
      expressing human papillomavirus type 16 E6 and E7 proteins.
AB  - The aim of the present study was to understand the genetic stability of a master
      seed bank (MSB) and a working seed bank (WSB) of an adenovirus vector vaccine
      expressing the human papillomavirus (HPV) type 16 E6 and E7 fusion proteins (Ad
      HPV16E6E7). Microscopic examination and viral infectious efficacy were used to
      measure the infectious titers of the Ad-HPV16E6E7 MSB and WSB. Polymerase chain
      reaction was used to analyze the stability of the Ad-HPV16E6E7 target gene
      insertion, while western blot analysis and immunofluorescence were used to assess
      the expression levels of the Ad-HPV16E6E7 target protein. A C57BL/6 mouse TC-1
      tumor cell growth inhibition model was used to evaluate the biological effect of
      Ad-HPV16E6E7 administration. The infectious titers of the Ad-HPV16E6E7 MSB and
      WSB were 6.31*109 IU/ml and 3.0*109 IU/ml, respectively. In addition, the
      expression levels of the inserted target genes and target proteins were found to
      be stable. In the mouse TC-1 tumor inhibition analysis, when the virus titers of
      the Ad-HPV16E6E7 MSB and WSB were 109 IU/ml, the tumor inhibition rate was 100%,
      which was significantly different when compared with the control group
      (chi2MSB=20.00 and chi2WSB=20.00; P<0.01). Therefore, the Ad-HPV16E6E7 vaccine
      seed bank is genetically stable and meets the requirements for vaccine
      development.

PMID- 25780404
TI  - Postconditioning with simvastatin decreases myocardial injury in rats following
      acute myocardial ischemia.
AB  - The aim of the present study was to investigate whether postconditioning with
      simvastatin attenuated myocardial ischemia reperfusion injury by inhibiting the
      expression of high mobility group box 1 (HMGB1) in rat myocardium following acute
      myocardial ischemia. In total, 30 male Sprague-Dawley rats were divided into sham
      operation (sham; n=10), acute myocardial infarction (AMI; n=10) and simvastatin
      (sim; n=10) groups. The AMI and sim groups were subjected to ischemia for 30 min,
      followed by reperfusion for 180 min. The rats in the sim group were administered
      20 mg/kg simvastatin intravenously 5 min prior to reperfusion. Subsequently, the
      infarct size, serum cardiac troponin (c-TnI), tumor necrosis factor (TNF)-alpha
      and myocardial malondialdehyde (MDA) levels and superoxide dismutase (SOD)
      activity were measured. Western blot analysis was used to detect the protein
      expression of HMGB1. Postconditioning with simvastatin was shown to decrease the
      infarct size and HMGB1 expression levels in the myocardium following AMI
      (P<0.05). In addition, postconditioning with simvastatin not only decreased the
      serum levels of c-TnI and TNF-alpha (P<0.05), but also inhibited the increase in
      MDA levels and the reduction in SOD activity (P<0.05). Therefore,
      postconditioning with simvastatin was shown to attenuate myocardial injury. The
      underlying mechanism may be associated with the downregulation of HMGB1
      expression in the ischemic myocardium.

PMID- 25780405
TI  - Early peritoneal lavage with ulinastatin improves outcome and enhances multi
      organ protection in a model of severe acute pancreatitis.
AB  - The aim of this study was to investigate the effect of early peritoneal lavage
      with ulinastatin on the outcome of a rat model of severe acute pancreatitis
      (SAP). A total of 80 male Wistar rats were randomly divided into the following
      groups: Sham-operated (C), SAP model (M), saline lavage (SL), intravenous
      ulinastatin (IU), early ulinastatin lavage (EUL) and late ulinastatin lavage
      (LUL). Intraperitoneal lavage or injection were performed immediately subsequent
      to the establishment of the SAP model in groups SL, IU and EUL and 3 h later in
      group LUL. Intraperitoneal lavage with or without ulinastatin was performed for 3
      h. The survival time of the rats in groups C, M, EUL and LUL was recorded over a
      12-h period and the median survival time was calculated. At 3 h after the
      induction of SAP, histopathological analyses were performed and the biochemical
      parameters of groups C, M, SL, IU and EUL were assessed. Groups EUL and LUL
      exhibited an increased median survival time compared with Group M, with the
      survival time of the rats in group EUL markedly longer than that in the group LUL
      rats. Group SL, IU and EUL rats were found to have reduced plasma activities of
      amylase, lipase, aspartate transaminase and alanine transaminase, with the
      biggest change observed in the group EUL rats. Furthermore, the intervention in
      groups SL and EUL was more effective at reducing creatinine and urea levels than
      that in group IU. Rats in group EUL exhibited a greater inhibition of the SAP
      induced increase in troponin T levels than rats in groups SL and IU. The
      pathological severity scores of the pancreas, liver, kidney and lung in group EUL
      were significantly lower than those in groups M and better than those in groups
      SL and IU. In conclusion, early intraperitoneal lavage with ulinastatin
      significantly improves the median survival time and protects multi-organ function
      in an SAP model.

PMID- 25780406
TI  - Electrocardiographic profile of adenosine pharmacological stress testing.
AB  - Adenosine stress testing in conjunction with radionuclide myocardial perfusion
      imaging has become a common approach for the detection of coronary artery
      diseases in patients who are unable to perform adequate levels of exercise.
      However, specific electrocardiographic alterations during the test have been
      rarely described. Using a Chinese population, the aim of the present study was to
      provide a detailed electrocardiographic profile of adenosine stress testing. The
      study population included 1,168 consecutive outpatients who had undergone
      adenosine-induced stress myocardial perfusion imaging. Electrocardiographic data
      during and immediately following the adenosine infusion were collected, and the
      corresponding myocardial perfusion images were assessed. During adenosine
      infusion, 174 transient and 47 persistent arrhythmic events occurred in 110
      patients (9.42%). Furthermore, frequent premature atrial contractions occurred in
      65 individuals and frequent premature ventricular contractions were observed in
      73 individuals. Atrioventricular block (AVB) occurred in 75 patients [first
      degree (I degrees ) AVB, 16; second degree (II degrees ) AVB, 58; third degree
      AVB, 1), while sinoatrial block occurred in eight patients. ST depression emerged
      in 69 patients. Patients with a baseline I degrees  AVB had an increased risk of
      a II degrees  AVB, and patients exhibiting baseline ST depression were more
      likely to have a further depressed ST segment during the stress test (odds ratio,
      28.68 and 5.01, respectively; both P<0.001). Following adenosine infusion, 10
      patients (0.86%) exhibited newly occurred arrhythmic events. However, no patient
      presented with acute myocardial infarction or sudden mortality. In conclusion,
      the results demonstrated that adenosine infusion was a safe method, despite the
      relatively high incidence of arrhythmic events. The majority of arrhythmias that
      occurred during infusion were transient, were reversible with the termination of
      infusion and did not indicate abnormal perfusion results.

PMID- 25780407
TI  - Substance P enhances the proliferation and migration potential of murine bone
      marrow-derived mesenchymal stem cell-like cell lines.
AB  - Due to the therapeutic characteristics of bone marrow (BM)-derived mesenchymal
      stem cells (MSCs), clinical trials are testing the use of autologous or
      allogeneic MSCs for the treatment of several conditions. These therapies require
      large numbers of MSCs and numerous studies are attempting to find substances that
      could enhance the egression of endogenous MSCs from the BM into the periphery and
      increase their proliferation in vivo and in vitro. It has been reported that
      substance P (SP) has the potential to increase the expansion of MSCs in vivo and
      to induce their mobilization from the BM into the periphery. The aim of the
      present study was to investigate the effects of SP on the migration and
      proliferation potential of two BM-derived MSC-like cell lines, ST2 and OP9. SP
      was found to induce the migration potential of ST2 cells in vitro. Furthermore,
      SP increased the proliferation of the MSCs cell line, OP9 cell line. Cyclin D1
      expression was observed to increase in the OP9 cells, indicating the activation
      of the cell cycle in response to SP. The upstream signals involved in these
      phenomena have yet to be elucidated, although previous studies have proposed the
      activation of the extracellular signal-regulated kinase-1/2 and Wingless/beta
      catenin pathways as possible mediators of the cellular proliferation of human
      MSCs in response to SP. The present results therefore suggest that SP would
      facilitate the obtainment of higher numbers of endogenous MSCs from patients or
      donors and/or shorten the process of in vitro expansion that could cause the MSCs
      to undergo changes in their innate therapeutic characteristics prior to their use
      in therapy.

PMID- 25780408
TI  - Mesenchymal stem cells expressing interleukin-18 suppress breast cancer cells in
      vitro.
AB  - Breast cancer is the most common malignancy among females throughout the world.
      Current treatments have unsatisfactory outcomes due to the dispersed nature of
      certain types of the disease. The development of a more effective therapy for
      breast cancer has long been one of the most elusive goals of cancer gene therapy.
      In the present study, human mesenchymal stem cells derived from umbilical cord
      (hUMSCs) genetically modified with interleukin 18 (IL-18) gene were used to study
      the effect of hUMSCs/IL-18 on the growth, migration and invasion of MCF-7 and
      HCC1937 cells in vitro. The hUMSCs could be efficiently modified by lentiviral
      systems and stably expressed IL-18 protein. hUMSCs/IL-18, but not hUMSCs without
      the IL-18 gene transduction, significantly suppressed the proliferation,
      migration and invasion of the MCF-7 and HCC1937 cells. The mechanism of this
      proliferation suppression may have involved the induction of G1- to S-phase
      arrest of the breast cancer cells by the hUMSCs/IL-18. In conclusion, hUMSCs/IL
      18 can suppress the proliferation, migration and invasion of breast cancer cells
      in vitro and may provide an approach for a novel antitumor therapy in breast
      cancer.

PMID- 25780409
TI  - Effect of low glycemic index food and postprandial exercise on blood glucose
      level, oxidative stress and antioxidant capacity.
AB  - Low glycemic index (GI) food and postprandial exercise are non-drug therapies for
      improving postprandial hyperglycemia. The present randomized, crossover study
      investigated the effect of low GI food combined with postprandial exercise on
      postprandial blood glucose level, oxidative stress and antioxidant capacity. A
      total of 13 healthy subjects were each used in four experiments: i) rice only
      (control), ii) salad prior to rice (LGI), iii) exercise following rice (EX) and
      iv) salad prior to rice and exercise following rice (MIX). The blood glucose
      level, oxidative stress and antioxidant capacity were then measured. At 60 min
      after the meal, the blood glucose level was observed to be increased in the MIX
      group compared with that in the LGI group. Furthermore, at 180 min, the
      antioxidant capacity was found to be reduced in the MIX group compared with those
      of the LGI and EX groups. These findings suggest that low GI food combined with
      postprandial exercise does not improve postprandial hyperglycemia. It may be
      necessary to establish optimal timing and intensity when combining low GI food
      with postprandial exercise to improve postprandial hyperglycemia.

PMID- 25780410
TI  - Survival of influenza A virus on contaminated student clothing.
AB  - The role of contaminated clothing in the transmission of influenza A virus during
      an epidemic period was investigated by examining the recovery of infectious
      influenza virus from experimentally virus-contaminated clothing, which had been
      subejected to routine wearing and washing for several months or years. The amount
      of infectious virus recovered from the nine types of clothing decreased with time
      and was shown to differ widely between clothing samples, when the contaminated
      clothing samples were maintained in uncovered glass Petri dishes in a safety
      cabinet under air blowing. These results indicate a dependence of virus
      transmissibility on the nature of the contaminated clothes. The difference in
      recovery was shown to have no significant correlation with the thickness or the
      materials of the clothing; however, a correlation was observed with the residual
      amount of water in the deposited virus preparation on the test clothing.

PMID- 25780411
TI  - Risk factors for non-curative resection of early gastric neoplasms with
      endoscopic submucosal dissection: Analysis of 1,123 lesions.
AB  - Although the frequency of residual disease and recurrence following endoscopic
      submucosal dissection (ESD) has markedly decreased, a few cases of residual
      disease and recurrence following ESD are still observed. The aims of the present
      study were to clarify the causes of non-curative resection and to investigate the
      risk factors. A total of 1,123 early gastric neoplasm lesions treated by ESD were
      investigated. Non-curative resection was defined as histological positivity of
      the resected margins, vascular invasion or failure of en bloc resection. Cases of
      non-curative resection were classified as being caused by one of three reasons:
      Inadequate technique, pre-procedural misdiagnosis or problems in the histological
      diagnosis. Following classification, the cases of non-curative and curative
      resection were compared based on a range of patient characteristics: Procedure
      time, and size, type and location of the lesions. The frequency of non-curative
      resection was 16% (182 lesions). Non-curative resection occurred due to
      inadequate technique in 59 cases, pre-procedural misdiagnosis in 88 cases and
      problems in the histological diagnosis in 35 cases. Multivariate analysis
      revealed that a large lesion size, long procedure time and inexperienced
      endoscopist were associated with a significantly higher risk of non-curative
      resection due to an inadequate technique. Furthermore, it was found that lesions
      located in the upper area of the stomach and cancer with submucosal invasion were
      associated with a significantly higher risk of non-curative resection due to pre
      procedural misdiagnosis. In conclusion, the present study has shown that the
      major reasons for non-curative resection are an inadequate technique and pre
      procedural misdiagnosis. The risk factors for these problems have been clarified.

PMID- 25780412
TI  - Anti-CD20 antibody induces the improvement of cytokine-induced killer cell
      activity via the STAT and MAPK/ERK signaling pathways.
AB  - There is a current requirement for novel therapeutic strategies for the treatment
      of hematopoietic tumors. Residual tumor cells are the main origin of tumor
      relapse. The aim of this study was to eliminate the residual tumor cells of
      hematopoietic tumors. Cytokine-induced killer (CIK) cells are used in
      immunotherapy to deplete the residual cells. However, it is necessary to increase
      the antitumor activity and clinical applicability of CIK cells. The present study
      investigated the antitumor activity of CIK cells to the SU-DHL2 human B-cell
      lymphoma and K562 human chronic myelogenous leukemia cell lines. CD3+CD56+ cells
      from healthy donors were expanded in culture with cytokines and anti-CD20
      monoclonal antibody (mAb; rituximab) to generate CIK cells. A preliminary
      investigation of their mechanism was then performed. The increase in the
      cytotoxicity of the CIK cells induced by the anti-CD20 mAb was associated with an
      increase in the expression of cytotoxic factors. The expression of components of
      the signal transducer and activator of transcription (STAT) and mitogen-activated
      protein kinase/extracellular signal-regulated kinase (MAPK/ERK) signaling
      pathways was found to increase. Upregulation of the expression of STAT1, STAT3
      and STAT5 is important as these co-stimulatory molecules enhance T-cell
      proliferation. Activation of the MAPK signaling pathway is a possible mechanism
      for the anti-apoptosis effect on the proliferation of CIK cells. In conclusion,
      anti-CD20 mAb may play an important role in the improvement of CIK-mediated
      cytotoxicity to tumor cells. These observations may aid in the improvement of the
      effects of immunotherapy in depleting the residual cells of hematopoietic tumors.
      Thus, the use of CIK cells cultured with anti-CD20 mAb could be a novel
      therapeutic strategy for the depletion of chemotherapy-resistant or residual
      cells in anaplastic large and B-cell lymphoma.

PMID- 25780413
TI  - Expression of platelet-derived growth factor in the vascular walls of patients
      with lower extremity arterial occlusive disease.
AB  - The aim of the present study was to quantitatively analyze the expression of
      platelet-derived growth factor (PDGF)-A and PDGF-B in the vascular walls of
      patients with lower extremity arterial occlusive disease (LEAOD). The expression
      levels of PDGF-A and PDGF-B in the lower extremity arteries of 19 LEAOD patients
      (case group) and three healthy subjects (control group) was determined using
      quantitative polymerase chain reaction. Intergroup comparisons revealed that the
      relative mRNA expression levels were higher in the case group, as compared with
      the control group, for PDGF-A (34.38+/-5.80 vs. 21.94+/-1.05; P<0.05) and PDGF-B
      (33.95+/-5.92 vs. 24.15+/-3.12; P<0.05). In addition, the expression of PDGF-A
      revealed a positive linear correlation with the expression of PDGF-B (P<0.05).
      Therefore, the expression levels of PDGF-A and PDGF-B were found to be higher in
      the vascular walls of LEAOD patients, while the expression of PDGF-A was found to
      correlate with the expression of PDGF-B. A significant increase in the expression
      levlels of PDGF-A and PDGF-B were observed in the vascular walls of patients with
      LEAOD, and the expression of PDGF-A was associated with the expression of PDGF-B.

PMID- 25780414
TI  - Opioid receptors and associated regulator of G protein signaling are involved in
      the cathartic colon of rats.
AB  - A cathartic colon is characteristic of slow transit constipation (STC), which can
      result following the long-term use of irritant laxatives. In the present study,
      the involvement of three opioid receptor subtypes (MU, MOR; delta, DOR; and
      kappa, KOR), regulator of G protein signaling 4 (RGS-4) and beta-arrestin-2 were
      investigated in the cathartic colon of rats. A rat model of a cathartic colon was
      established by feeding the animals with phenolphthalein, while normal rats were
      used as a control. The mRNA and protein expression levels of the opioid
      receptors, RGS-4 and beta-arrestin-2 were detected in the rat colon using semi
      quantitative reverse transcription polymerase chain reaction and western blot
      analysis, respectively. The rat model of a cathartic colon was successfully
      established using the phenolphthalein stimulus, and was shown to result in
      shrunken myenteric neurons and loose muscle fibers in the intestinal wall. The
      mRNA and protein expression levels of the three opioid receptor subtypes, RGS-4
      and beta-arrestin-2 were significantly higher in the cathartic colon group when
      compared with the levels in the normal control group (all P<0.01). With regard to
      the protein expression levels, MOR protein increased 2.4 fold, DOR expression
      increased 1.5 fold, KOR levels increased 1.5 fold, RGS-4 protein increased 3.5
      fold and beta-arrestin-2 expression increased 2.0 fold. Therefore, the expression
      levels of opioid receptors were found to increase in the cathartic colons of the
      rats, indicating that opioid receptors and downstream RGS-4 and beta-arrestin-2
      signaling may play an important role in the pathogenesis of STC.

PMID- 25780415
TI  - Effect of heterologous bone marrow mononuclear cell transplantation on midpalatal
      expansion in rats.
AB  - The aim of this study was to explore whether bone marrow mononuclear cell (BMMC)
      transplantation is able to accelerate the bone remodeling induced by midpalatal
      expansion in rats. A total of 48 male Sprague-Dawley rats (mean weight, 208.36+/
      7.32 g) were divided into control and midpalatal expansion with or without BMMC
      transplantation groups. Histological and morphological changes were observed in
      each group. The osteogenic activities and differential potentials of the
      transplanted BMMCs labeled with bromodeoxyuridine in the midpalatal bone tissue
      were assessed by osteocalcin expression. The receptor activator of nuclear factor
      kappaB ligand (RANKL)/osteoprotegerin (OPG) ratio was determined by reverse
      transcription-quantitative polymerase chain reaction (RT-qPCR) to reflect the
      equilibrium between bone resorption and formation. The results demonstrated that
      the width of the maxillary dental arch increased distinctly within 2 weeks of
      midpalatal expansion with BMMC transplantation. The morphology of the midpalatal
      suture in this group changed significantly; the cartilage was completely replaced
      by fibrous-like tissue expressing osteocalcin. The palatal bone was reorganized
      from a cancellous form into a mature compact structure after an additional 2-week
      relapse period. Immunostaining results indicated that the heterologous
      transplanted BMMCs survived and differentiated into osteoblasts during the
      remodeling induced by midpalatal expansion. The RANKL/OPG expression ratio
      significantly decreased after 2 weeks of midpalatal expansion with BMMC
      transplantation due to the inhibition of RANKL expression. Heterologous BMMC
      transplantation appears to accelerate the midpalatal bone remodeling induced by
      expansion of the rats through increasing the number of osteoprogenitor cells and
      regulating the RANKL-OPG signaling pathway.

PMID- 25780416
TI  - Separation and confirmation of nine Enterobacteriaceae strains that carry the
      blaNDM-1 gene.
AB  - The aim of the present study was to confirm the existence of carbapenem-resistant
      Enterobacteriaceae carrying the blaNDM-1 gene in clinics in Hainan province,
      China. Collected clinical bacterial isolates that were Enterobacteriaceae strains
      suspected of producing carbapenemase were used as experimental strains. Drug
      resistance to imipenem, meropenem and other antibacterial agents was tested.
      Imipenem/imipenem inhibitor (IP/IPI) E-testing was conducted to identify the
      bacterial strains that produced metallo-beta-lactamases. The blaNDM-1 drug
      resistance gene was amplified by polymerase chain reaction (PCR), and agarose gel
      electrophoresis (AGE) and sequencing were conducted to identify the products. The
      species of the strains carrying the blaNDM-1 gene were determined using a
      biochemical identification system. Through the IP/IPI E-test, 21 of the 30
      collected Enterobacteriaceae strains were found to be positive, indicating that
      70% of the strains produced metallo-beta-lactamases. Following blaNDM-1 gene PCR
      amplification, AGE and sequencing tests confirmed that nine of the strains
      carried the blaNDM-1 drug resistance gene. The biochemical identification system
      indicated that four of the strains were Klebsiella pneumoniae, two were
      Escherichia coli, two were Enterobacter cloacae and one was Enterobacter
      aerogenes. Drug susceptibility testing in vitro demonstrated that the strains
      were 100% resistant to a broad spectrum antibiotic plus lactamase inhibitor,
      cephalosporins and carbapenems. However, they had high sensitivity rates to
      polymyxin B and tigecycline of 100 and 88.9%, respectively. The sensitivity rate
      to amikacin was also high at 77.8%, whereas sensitivity to ciprofloxacin and
      gentamicin was moderate at rates of 44.4 and 33.3% respectively. This clinical
      study of Enterobacteriaceae strains that carry the blaNDM-1 gene in Hainan shows
      a bacterial tolerance that is different from that in previous studies, which
      requires further in-depth study.

PMID- 25780417
TI  - Loss of plexin-B3 in hepatocellular carcinoma.
AB  - Plexins are the primary receptors of semaphorins, and participate in the majority
      of intracellular pathways triggered by semaphorins, including the regulation of
      cell adhesion and the motility of numerous cell types. Recently, several studies
      have reported that plexins can significantly affect different aspects of cancer
      cell biology, and the aberrant expression of plexins has been observed in a wide
      variety of tumor types. However, the expression and role of plexin-B3 in
      hepatocellular carcinoma (HCC) is yet to be investigated. In the present study,
      plexin-B3 expression was measured in 14 paired HCC samples and the corresponding
      adjacent non-cancerous tissue by quantitative polymerase chain reaction and
      western blot analysis. The results indicated that the mRNA and protein expression
      levels of plexin-B3 were downregulated in HCC samples when compared with the
      corresponding adjacent non-cancerous tissue. In order to elucidate the
      correlation between clinicopathological data and the expression of plexin-B3 in
      patients with HCC, 84 HCC archived specimens were analyzed by
      immunohistochemistry (IHC). The IHC results revealed that the protein expression
      level of plexin-B3 was lower in the HCC samples compared with the corresponding
      adjacent non-cancerous tissue, and plexin-B3 underexpression was correlated with
      the patient gender and tumor size. In conclusion, these results indicated that
      loss of plexin-B3 in HCC may be of predictive value for the occurrence and
      progression of HCC. Thus, plexin-B3 may be a promising biomarker for the
      diagnosis and treatment of tumors in the future.

PMID- 25780418
TI  - Picroside II protects rat kidney against ischemia/reperfusion-induced oxidative
      stress and inflammation by the TLR4/NF-kappaB pathway.
AB  - Picroside II possesses a wide range of pharmacological effects and has been
      demonstrated to ameliorate cerebral ischemia and reperfusion (I/R) injury.
      However, its effects on renal I/R injury remain unclear. In the present study,
      the role of picroside II in attenuating oxidative stress and the inflammatory
      response in a rat model of renal I/R injury was investigated. Sprague Dawley rats
      were subjected to 45 min of ischemia followed by 24 h of reperfusion. Prior to
      reperfusion, the rats were treated with picroside II or an equal volume of
      phosphate-buffered saline. Renal function and histological changes were compared
      and the relevant parameters of oxidative stress and inflammation were detected.
      The expression of toll-like receptor 4 (TLR4) and nuclear factor kappaB (NF
      kappaB; p65) were assessed by immunohistochemistry and western blotting. It was
      observed that renal function was significantly improved by treatment with
      picroside II. Morphological analysis indicated that picroside II clearly reduced
      tissue damage and the expression of TLR4 and NF-kappaB. Reverse transcription
      quantitative polymerase chain reaction demonstrated that picroside II inhibited
      the increase of tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta and
      intercellular adhesion molecule (ICAM)-1 expression induced by I/R injury.
      Western blot analysis indicated that the expression levels of TLR4 and NF-kappaB
      were significantly downregulated in the picroside II group compared with those in
      the I/R group. These results indicate that picroside II treatment suppressed the
      TLR4/NF-kappaB signaling pathway, protecting renal tissue against I/R-induced
      oxidative stress and inflammatory response.

PMID- 25780419
TI  - Comparison between remifentanil and dexmedetomidine for sedation during modified
      awake fiberoptic intubation.
AB  - Cricothyroid membrane injections and the application of a coarse fiberoptic
      bronchoscope (FOB) below the vocal cords for topical anesthesia have a number of
      limitations for certain patients. Thus, the aim of the present observational
      study was to assess the effect of a novel modified topical anesthesia method
      using the effective sedation drugs, remifentanil (Rem) or dexmedetomidine (Dex),
      during awake fiberoptic orotracheal intubation (AFOI). In total, 90 adult
      patients, who had been classified as American Society of Anesthesiologists I-II,
      were included in the study. The patients had anticipated difficult airways and
      were to undergo orotracheal intubation for elective surgery. The patients were
      enrolled in the double-blinded randomized pilot study and received Rem or Dex for
      sedation during the modified AFOI procedure. The two groups received 2% lidocaine
      for topical anesthesia via an epidural catheter, which was threaded through the
      suction channel of the FOB. The main clinical outcomes were evaluated by graded
      scores representing the conditions for intubation and post-intubation. Additional
      parameters analyzed included airway obstruction, hemodynamic changes, time
      required for intubation, amnesia level and subjective satisfaction. All 90
      patients were successfully intubated using the modified AFOI technique. The
      comfort scores and airway events during intubation did not significantly differ
      between the two groups. However, the Rem group experienced less coughing, and
      less time was required for tracheal intubation when compared with the Dex group.
      No statistically significant differences were observed in the changes to the mean
      arterial pressure and heart rate at any time point between the two groups.
      Therefore, the current study demonstrated that the modified AFOI method is
      feasible and effective for difficult airway management, and that Dex and Rem
      exhibit similar efficacy as adjuvant therapies.

PMID- 25780420
TI  - Cbl-b-regulated extracellular signal-regulated kinase signaling is involved in
      the shikonin-induced apoptosis of lung cancer cells in vitro.
AB  - Shikonin (SK), a naturally occurring naphthoquinone, exhibits antitumor activity.
      However, its precise mechanisms of action are unknown. In the present study, the
      effects of SK on NCI-H460 human lung cancer cells were investigated. It was found
      that SK reduced cell viability and induced apoptosis in the NCI-H460 cells.
      Additionally, SK inhibited extracellular signal-regulated kinase (ERK) activity,
      which indicates that inhibition of the ERK pathway is probably one of the
      mechanisms by which SK induced NCI-H460 cell apoptosis. The expression of Cbl-b
      was significantly increased by treatment with SK for 4 h, and gradually increased
      to a maximal level at 24 h; the time taken for the upregulation of Cbl-b protein
      was in accordance to that required for the downregulation of phospho (p)-ERK
      protein. The Cbl inhibitor Ps341 reversed the SK-induced downregulation of p-ERK
      and apoptosis of NCI-H460 cells. These results indicate that Cbl-b potentiates
      the apoptotic action of SK by inhibiting the ERK pathway in lung cancer cells.

PMID- 25780421
TI  - Knockdown of autophagy-related gene LC3 enhances the sensitivity of HepG2 cells
      to epirubicin.
AB  - Hepatocellular carcinoma (HCC) is a major public health problem. Despite new
      chemotherapeutic treatments, drug resistance remains a major clinical obstacle to
      successful treatment in HCC patients. Therefore, novel therapeutic targets and
      new modalities of treatment are urgently required. In this study, tetracycline
      inducible lentivirus-mediated RNA interference (RNAi) was employed to knock down
      microtubule-associated protein 1 light chain 3 (LC3) gene, which encodes a key
      protein in the induction of autophagy, to study the protective function of
      autophagy in liver cancer tolerant to epirubicin. The effect of combined
      treatment with lentiviral shLC3 and epirubicin on cell growth and
      chemosensitivity to epirubicin in the HCC cell line HepG2 were also investigated.
      The results demonstrated that lentivirus-mediated LC3 silencing significantly
      inhibited cell proliferation. In addition, combined treatment with lentiviral
      shLC3 and epirubicin significantly decreased the survival rate of HepG2 cells,
      compared with that following treatment with either agent alone. Overall, the
      results from this study suggest for the first time, to the best of our knowledge,
      that LC3 plays a key role in HCC tumorigenesis, and is a novel therapeutic target
      for HCC.

PMID- 25780422
TI  - Effect of lithium ions on cementoblasts in the presence of lipopolysaccharide in
      vitro.
AB  - The applications of lithium ions as an agent to facilitate bone formation have
      been widely documented; however, the effect of lithium ions in the periodontitis
      model has not yet been elucidated. The aim of the present study, therefore, was
      to investigate the effect of single lithium ions in the presence of
      lipopolysaccharide (LPS). A periodontitis model was induced in cementoblasts
      using LPS. The cytotoxic effect of the lithium ions on the cementoblasts was
      studied through the MTT assay. Alkaline phosphatase analysis and alizarin red
      staining were performed to investigate the effect of the lithium ions on
      differentiation. To examine the effect of lithium ions on osteoclastogenesis,
      osteoprotegerin (OPG) and receptor activator of nuclear factor-kappaB ligand
      (RANKL) mRNA and protein expression levels were assessed using reverse
      transcription-polymerase chain reaction analysis and ELISA, respectively.
      Compared with the effect induced by lithium ions on normal cementoblasts,
      proliferation and differentiation were downregulated following the co-incubation
      of the cementoblasts with LPS and lithium ions. Furthermore, the lithium ions
      appeared to alter osteoclastogenesis by regulating the OPG/RANKL ratio. In
      conclusion, the present findings suggest that lithium ions can downregulate
      proliferation and differentiation in a periodontitis model. Further studies
      should be undertaken prior to the acceptance of lithium ions for use in the
      clinic.

PMID- 25780423
TI  - Testosterone suppresses ventricular remodeling and improves left ventricular
      function in rats following myocardial infarction.
AB  - Men with congestive heart failure (CHF) have relatively low testosterone levels.
      Several studies demonstrated that testosterone treatment increases cardiac output
      and reduces peripheral vascular resistance. However, the effects of testosterone
      on heart function, cardiomyocyte apoptosis and ventricular remodeling have not
      been fully elucidated. This study was conducted to investigate the effects of
      testosterone on heart function, cardiomyocyte apoptosis and ventricular
      remodeling in male rats post-myocardial infarction. A total of 86 male rats were
      randomly assigned to undergo ligation of the coronary artery (n=70) or
      pseudosurgery (n=16). After 6 weeks, a left ventricular ejection fraction (LVEF)
      of <=45% was defined as a successful model of CHF. The model rats were randomly
      assigned to 3 groups, namely low-dose testosterone (TU), high-dose TU and placebo
      (PL) groups. After treatment for 12 weeks, the expression of several mRNA
      transcripts in myocardial tissue was measured by quantitative polymerase chain
      reaction. Immunofluorescence was used to measure myocardial caspase-3 expression.
      Compared to the PL group, LVEF was significantly improved in the TU treatment
      groups. Moreover, the mRNA expression of atrial natriuretic peptide, brain
      natriuretic peptide, matrix metalloproteinase-2 and sarcoendoplasmic reticulum
      Ca2+-ATPase 2a was significantly reduced, while the mRNA expression of glycogen
      synthase kinase 3beta and tissue inhibitor of metalloproteinase-2 was markedly
      increased in the TU groups. TU treatment also significantly reduced caspase-3
      expression. Therefore, different doses of TU suppressed ventricular remodeling
      and improved left ventricular function, reduced apoptosis and prevented mortality
      in a CHF rat model.

PMID- 25780424
TI  - Effects of bone marrow-derived mesenchymal stem cells transplanted via the portal
      vein or tail vein on liver injury in rats with liver cirrhosis.
AB  - The aim of the present study was to compare the effects of bone marrow-derived
      mesenchymal stem cells (BMSCs) transplanted via the portal vein or tail vein on
      liver injury in rats with liver cirrhosis. BMSCs were isolated from rat bone
      marrow and labeled with green fluorescent protein (GFP). Then, the labeled BMSCs
      were injected into rats with liver injury via the portal vein or tail vein. Two
      weeks after transplantation, three rats in each group were sacrificed to test the
      distribution of GFP in the liver and the serum levels of alanine aminotransferase
      (ALT), aspartate aminotransferase (AST) and albumin. Six weeks later, the
      remaining rats were sacrificed, and serum ALT, AST, albumin, hyaluronic acid
      (HA), laminin (LN) and procollagen type III (PC-III) levels were measured. The
      expression of albumin in the liver was analyzed by immunohistochemistry. Two
      weeks after BMSC transplantation, GFP-positive cells were detected in the livers
      of rats with BMSCs transplanted via the portal vein and tail vein. Compared with
      pre-transplantation levels, the ALT levels of the groups with BMSC
      transplantation via the portal vein and tail vein were significantly decreased
      after two and six weeks of BMSC transplantation (P<0.05), whereas the AST and
      albumin levels were not significantly different at two weeks after BMSC
      transplantation in the two groups (all P>0.05). However, the AST and albumin
      levels were significantly reduced at six weeks after BMSC transplantation (all
      P<0.05). At six weeks after BMSC transplantation, the serum HA, LN and PC-III
      levels in rats transplanted with BMSCs via the portal vein or tail vein had
      decreased significantly (all P<0.05), as compared with the levels prior to BMSC
      transplantation. BMSCs transplanted via the portal vein and tail vein achieved
      similar improvements in liver function in rats with liver cirrhosis, which
      suggests that peripheral venous administration is a convenient and effective
      route for BMSC transplantation.

PMID- 25780425
TI  - Primary primitive neuroectodermal tumor arising in the mesentery and ileocecum: A
      report of three cases and review of the literature.
AB  - Primitive neuroectodermal tumor (PNET) is most commonly encountered in the soft
      tissue or bone in children and young adults, and its involvement in the
      intestines is exceedingly rare. To the best of our knowledge, eighteen cases have
      been reported to date. The present study reports three cases of PNET arising in
      the mesentery and ileocecum in 59- and 22-year-old males and a 36-year-old
      female. Computed tomography revealed a solid mass in the lower abdomen, with
      areas of cystic changes. Microscopically, the tumors were composed of small round
      cells arranged in sheets and rosettes with scant cytoplasm, hyperchromatic nuclei
      and a high mitotic rate. The tumor cells were immunopositive for CD99 and FLI1.
      EWS/FLI1 translocations were detected in all cases. Case 1 and case 2 underwent
      tumor resection without any preoperative radiotherapy, chemotherapy or biological
      therapy. Case 3 underwent tumor resection and received eight cycles of IAP
      chemotherapy (2.0 mg ifosfamide, 80 mg epirubicin, 30 mg cisplatin 30mg). Case 3
      was followed up for 34 months until they succumbed to peritoneal recurrence,
      whereas the other cases were not followed up. The incidence of these small round
      cell tumors in the intestinal system, their clinical and pathological features
      and differential diagnosis are discussed with a review of the literature.

PMID- 25780426
TI  - Volatile oils of Chinese crude medicines exhibit antiparasitic activity against
      human Demodex with no adverse effects in vivo.
AB  - Demodex is a type of permanent obligatory parasite, which can be found on the
      human body surface. Currently, drugs targeting Demodex usually result in adverse
      effects and have a poor therapeutic effect. Thus, the aim of the present study
      was to investigate the use of Chinese crude medicine volatile oils for targeting
      and inhibiting Demodex in vitro. The volatile oils of six Chinese crude medicines
      were investigated, including clove, orange fruit, Manchurian wildginger, cinnamon
      bark, Rhizome Alpiniae Officinarum and pricklyash peel, which were extracted
      using a distillation method. The exercise status of Demodex folliculorum and
      Demodex brevis and the antiparasitic effects of the volatile oils against the two
      species were observed using microscopy. A skin irritation test was used to
      examine the irritation intensity of the volatile oils. In addition, an acute
      toxicity test was utilized to observe the toxicity effects of the volatile oils
      on the skin. Xin Fumanling ointment was employed as a positive control to
      identify the therapeutic effects of the volatile oils. The results indicated that
      all six volatile oils were able to kill Demodex efficiently. In particular, the
      clove volatile oil was effective in inducing optimized anti-Demodex activity. The
      lethal times of the volatile oils were significantly decreased compared with the
      Xin Fumanling ointment (P<0.05). Furthermore, the skin irritation test results
      indicated that the clove volatile oil did not trigger any irritation (0.2 and 0.3
      points for intact and scratched skin, respectively), and had a safety equal to
      that of distilled water. There were not any adverse effects observed following
      application of the clove volatile oil on the intact or scratched skin. In
      conclusion, the volatile oils of Chinese crude medicines, particularly that of
      clove, demonstrated an evident anti-Demodex activity and were able to kill
      Demodex effectively and safely in vivo.

PMID- 25780427
TI  - A lack of association between the IKZF2 rs12619285 polymorphism and coronary
      heart disease.
AB  - The IKZF2 rs12619285 polymorphism is associated with the eosinophil count, which
      has multidimensional functions in the pathogenesis of coronary heart disease
      (CHD). The aim of the present study was to investigate the contribution of the
      IKZF2 rs12619285 polymorphism to the risk of CHD in a Han Chinese population. In
      total, 721 CHD cases and 631 non-CHD controls were recruited for an association
      study of the IKZF2 rs12619285 polymorphism. Genotyping was performed using the
      melting temperature-shift polymerase chain reaction method. No statistically
      significant association was observed between the IKZF2 rs12619285 polymorphism
      and CHD (odds ratio, 1.139, 95% confidence interval, 0.927-1.334; P=0.17). In
      addition, subgroup analyses by gender or age were unable to identify any
      association between IKZF2 rs12619285 and CHD (P>0.05), and there was no
      significant correlation between IKZF2 rs12619285 and the severity of CHD
      (P>0.05). The power of the case-control study was determined to be 63.3%. In
      addition, the G allele frequency was calculated as 63.6% in the Han Chinese
      population, which was similar to the 59.3% recorded for the HapMap Chinese
      population of Han Chinese individuals living in Beijing, compared with 24.3% in
      European descendents (HapMap-CEU). Therefore, the results indicated that the
      IKZF2 rs12619285 polymorphism was not associated with CHD in a Han Chinese
      population. The discrepancy in the association between rs12619285 and CHD may be
      due to the ethnic differences between Han Chinese and European populations.

PMID- 25780428
TI  - Super-compact treatment with a high dose of moxifloxacin in patients with drug
      resistant tuberculosis and its resistance mechanisms.
AB  - The aim of this study was to investigate the curative effect and resistance
      mechanisms of high-dose moxifloxacin in the short-term treatment of multidrug
      resistant tuberculosis. A total of 92 patients with multidrug-resistant
      tuberculosis were randomly selected and divided into groups A and B (n=46 per
      group). The two groups received moxifloxacin treatment with the same dose in
      total. Group A received a short course of treatment with moxifloxacin (0.6 g/day
      for 6 months), whereas group B received normal moxifloxacin treatment (0.4 g/day
      for 9 months). Sputum negative conversion, foci absorption, cavity closure and
      adverse reactions in the two groups were observed, and the drug resistance
      mechanism of tuberculosis to moxifloxacin treatment was investigated. Following
      the treatment, the curative rate of group A was 82.61%, and the curative rate of
      group B was 84.78%; there was no statistically significant difference between the
      two groups (P>0.05). The rates of sputum negative conversion, foci absorption and
      cavity closure were not significantly different between the two groups (P>0.05).
      However, the rates of reduction in peripheral white blood cell counts, liver
      function damage and adverse reactions, including symptoms affecting the
      gastrointestinal and nervous systems, were significantly lower in group A than in
      group B (P<0.05). The expression levels of the antigen-presenting functional
      molecules CD80 and CD40 on the surfaces of mononuclear cells were higher in group
      A than in group B (P<0.05), whereas the difference in HLA-DR expression between
      groups A and B was not significant (P>0.05). In conclusion, short-term treatment
      with a high dose of moxifloxacin is effective for multidrug-resistant
      tuberculosis, and its advantages are a reduction in the incidence of drug
      associated adverse reactions and a lack of drug resistance.

PMID- 25780430
TI  - X-linked hyper-IgM syndrome with eosinophilia in a male child: A case report.
AB  - The hyper-IgM syndromes (HIGMs) are a group of primary immune deficiency diseases
      characterized by a normal or elevated serum level of IgM and low or absent serum
      levels of IgG, IgA and IgE. Here, we report a case of X-linked HIGM with a new
      CD40L gene mutation presenting with eosinophilia. The patient experienced
      recurrent pneumonia and acute respiratory distress syndrome (ARDS) from 4 months
      of age. Immunological evaluation revealed a normal level of serum IgM, with
      significantly low levels of serum IgG and IgA. Genetic analysis of the CD40L gene
      revealed a splice mutation in exon 5 at the nucleotide position 410 (c.410-2A>G),
      which has never been reported previously in the literature. Following treatment
      with regular intravenous immunoglobulin (IVIG) replacement therapy every 3 to 4
      weeks and infection prophylaxis with trimethoprim-sulfamethoxazole during follow
      up, the patient's immunoglobulin level returned to normal with no pulmonary
      infection. The eosinophil count also returned to normal after a small dose of
      steroid agent treatment was administered orally for 5 months. In summary, X
      linked hyper-IgM syndrome with CD40L gene mutation presenting with eosinophilia
      may be successfully treated using IVIG replacement therapy and a small dose of
      steroid agent.

PMID- 25780429
TI  - Neuroprotective effect of the active components of three Chinese herbs on brain
      iron load in a mouse model of Alzheimer's disease.
AB  - Alzheimer's disease (AD) is a neurodegenerative brain disorder and the most
      common cause of dementia. New treatments for AD are required due to its
      increasing prevalence in aging populations. The present study evaluated the
      effects of the active components of Epimedium, Astragalus and Radix Puerariae on
      learning and memory impairment, beta-amyloid (Abeta) reduction and brain iron
      load in an APPswe/PS1DeltaE9 transgenic mouse model of AD. Increasing evidence
      indicates that a disturbance of normal iron homeostasis may contribute to the
      pathology of AD. However, the underlying mechanisms resulting in abnormal iron
      load in the AD brain remain unclear. It has been hypothesized that the brain iron
      load is influenced by the deregulation of certain proteins associated with brain
      iron metabolism, including divalent metal transporter 1 (DMT1) and ferroportin 1
      (FPN1). The present study investigated the effects of the active components of
      Epimedium, Astragalus and Radix Puerariae on the expression levels of DMT1 and
      FPN1. The treatment with the active components reduced cognitive deficits,
      inhibited Abeta plaque accumulation, reversed Abeta burden and reduced the brain
      iron load in AD model mice. A significant increase was observed in the levels of
      DMT1-iron-responsive element (IRE) and DMT1-nonIRE in the hippocampus of the AD
      mouse brain, which was reduced by treatment with the active components. In
      addition, the levels of FPN1 were significantly reduced in the hippocampus of the
      AD mouse brain compared with those of control mice, and these levels were
      increased following treatment with the active components. Thus, the present study
      indicated that the active components of Epimedium, Astragalus and Radix Puerariae
      may exert a neuroprotective effect against AD by reducing iron overload in the AD
      brain and may provide a novel approach for the development of drugs for the
      treatment of AD.

PMID- 25780431
TI  - Study on extracellular matrix metalloproteinase inducer and human epidermal
      growth factor receptor-2 protein expression in papillary thyroid carcinoma using
      a quantum dot-based immunofluorescence technique.
AB  - The aim of the present study was to investigate the association of extracellular
      matrix metalloproteinase inducer (EMMPRIN) and human epidermal growth factor
      receptor (HER)-2 protein expression in papillary thyroid carcinoma with lymph
      node metastasis (LNM), as well as the correlation between the two types of
      protein expression. A quantum dot-based immunofluorescence technique was used to
      detect EMMPRIN and HER-2 protein expression in 75 papillary thyroid carcinoma
      cases (including 70 cases of papillary thyroid carcinoma tissues and 5 cases of
      peri-tumor tissues). The positive rate and expression of EMMPRIN and HER-2 were
      compared and observed. The positive rate of EMMPRIN was 75.71% in papillary
      thyroid carcinoma tissues and 20.00% in peri-tumor tissues (P<0.05). The positive
      rate of HER-2 was 45.71% in papillary thyroid carcinoma tissues and 0% in peri
      tumor tissues (P>0.05). The expression of EMMPRIN and HER-2 in papillary thyroid
      carcinoma was significantly associated with LNM (P<0.05). In addition, in the 70
      papillary thyroid carcinoma tissues, the expression of EMMPRIN and HER-2 was
      positively and significantly correlated. In conclusion, this study demonstrates
      that the co-evolution of EMMPRIN and HER-2 may promote the occurrence and
      development of papillary thyroid carcinoma and LNM.

PMID- 25780432
TI  - Clinical study of cerebral palsy in 408 children with periventricular
      leukomalacia.
AB  - This study aimed to investigate the high risk factors, cerebral palsy (CP)
      subtypes and comorbidities of periventricular leukomalacia (PVL). Based on
      treatment conditions at a specialist hospital, a cross-sectional clinical study
      and retrospective analysis of computed tomography and magnetic resonance imaging
      examinations was conducted to evaluate the risk factors, subtypes and
      comorbidities of CP in children with PVL. Among the 408 children with PVL, 8.58%
      were born with a weight of <=1,500 g and 44.36% were born with a weight of
      >=2,500 g. In addition, 36.76% of these children had a gestational age of <=32
      weeks and 37.75% had a gestational age of >=37 weeks. The proportion of the
      children born with various high risk factors was 95.59%, including perinatal
      infections and hypoxia. Severe PVL was observed in preterm infants (63.41% with a
      gestational age of <28 weeks and 21.95% with a gestational age of 28-30 weeks)
      and low-birth weight infants, which were prone to quadriplegia (43.90%). The
      common comorbidities included visual and auditory disorders, epilepsy, mental
      retardation and language barriers. Visual and auditory disorders (26.96%) were
      the most common comorbidities. PVL was identified primarily in premature and low
      birth weight infants. The degree of PVL was found to be negatively correlated
      with gestational age and birth weight. The degree of PVL in the full-term infants
      correlated with exposure to infections or hypoxia. Quadriplegia is common among
      the various subtypes of CP. Visual and hearing disorders are the most common
      comorbidities of CP; these comorbidities occurred most frequently with
      quadriplegia.

PMID- 25780433
TI  - Piperlongumine reverses doxorubicin resistance through the PI3K/Akt signaling
      pathway in K562/A02 human leukemia cells.
AB  - Drug resistance is an important obstacle to human leukemia therapeutics.
      Piperlongumine has previously demonstrated the ability to suppress certain human
      tumor processes; however, the ability of piperlongumine to reverse the drug
      resistance of human leukemia and its mechanism of action have not yet been
      clearly elucidated. In this study, the doxorubicin resistance reversal effect of
      piperlongumine on K562/A02 human leukemia cells and the underlying mechanism were
      investigated. The results indicated that piperlongumine promoted doxorubicin
      sensitivity, apoptosis, the intracellular accumulation of rhodamine-123, the
      activities of caspase-3 and -8, and the expression of reactive oxygen species,
      p53, p27 and p-PTEN. Furthermore, it suppressed the expression of P-glycoprotein,
      MDR1, MRP1, survivin and p-Akt, and the transcriptional activities of NF-kappaB
      and twist, and arrested the cell cycle in the G2/M phase. The results indicate
      that piperlongumine has the potential to be used as a therapeutic agent for human
      leukemia.

PMID- 25780434
TI  - Oxytocin in the paraventricular nucleus attenuates incision-induced mechanical
      allodynia.
AB  - Oxytocin (OT) neurons localized in the paraventricular nucleus (PVN) and
      supraoptic nucleus (SON) send fibers to the brain and spinal cord. While most
      previous studies have looked at the role of OT in chronic pain, few have
      investigated the role of OT in acute pain, particularly postoperative pain. In
      the present study, the role of OT in incision-induced allodynia was explored for
      the first time, using a rat incisional pain model. Immunohistochemical staining
      showed that, compared with the baseline (prior to incision) measurements, the OT
      content in the PVN was significantly decreased at 0.5, 1.0 and 3.0 h post
      incision and returned to the baseline level at 6.0 h post-incision. By contrast,
      there was no significant difference in the OT content in the SON prior to and
      subsequent to incision. A dose-dependent inhibition of mechanical
      hypersensitivity was detected 30 min after intracerebroventricular injection of
      OT (100, 400 or 600 ng) and lasted for 3.0 h. No significant difference was
      noted, however, between the intrathecal OT injection group (600 ng) and the
      control group. In conclusion, the present study provides the first in vivo
      evidence that OT in the PVN predominantly attenuates incision-induced mechanical
      allodynia at the supraspinal, rather than the spinal, level. This suggests that
      OT is involved in supraspinal analgesia for postoperative pain.

PMID- 25780435
TI  - Blockade of Plasmodium falciparum erythrocyte invasion: New assessment of anti
      Plasmodium falciparum reticulocyte-binding protein homolog 5 antibodies.
AB  - There is great interest in any new discoveries in malaria vaccine research.
      Plasmodium falciparum reticulocyte-binding protein homolog 5 (PfRH5) shows
      promise in this area and may be used together with other merozoite antigens as a
      potential vaccine. In the present study, a bioinformatics prediction approach was
      applied to a PfRH5 B-cell epitope, and two B-cell epitope distributions were
      selected. Antibodies against the two PfRH5 distributions were obtained and the
      growth activity inhibition was measured. No inhibition of the P. falciparum CY
      strain was found, but the growth of the P. falciparum 3D7 strain was inhibited by
      all of the antibodies, in contrast to the results of other studies. It was
      additionally found that certain quantities of protein led to the inhibition of
      the parasitic invasion. Equally noteworthy was that the survival time of the
      group immunized with a portion of PfRH5 was significantly longer than that of the
      group immunized with the full-length protein, following infection by P. berghei
      ANKA. The present study produced conflicting results in in vitro and in vivo
      experiments, although the accuracy of the evaluation may be lessened due to the
      use of a murine malaria model. The findings of the present study may indicate
      that PfRH5 may not be suitable in malaria vaccine research.

PMID- 25780436
TI  - Clinical characteristics and therapeutic evaluation of childhood myasthenia
      gravis.
AB  - This study aimed to analyze the clinical characteristics, classification and
      treatment of childhood myasthenia gravis (MG) and address the prognosis through
      follow-up. The clinical data of 135 children with MG were grouped according to
      clinical type and therapeutic drugs, retrospectively analyzed and prospectively
      monitored. Of the 135 MG patients, 85.2% had type I (ocular type), with only 4.2%
      progressing to systemic MG; 13.4% had type II (general type); and 1.5% had type
      III (fulminating type). Relapse occurred in 46.1% of the 102 patients that were
      followed up. The positive rate for the primary acetylcholine receptor antibody
      was 40.19%, without significant differences among clinical subtypes. The positive
      rate of the repetitive nerve stimulation frequency test by electromyography was
      37.97%. Decreased expression of CD4+, CD8+, or CD3+ was present in 71% of the
      patients. Thymic hyperplasia was present in 5.93% of the patients, while 1.48%
      had thymoma. Steroid treatment was effective in the majority of the patients.
      Ocular type MG was common in this cohort of patients. The incidence and mortality
      of myasthenia crisis were low, the presence of concurrent thymoma was rare and
      only a limited number of children developed neurological sequelae.

PMID- 25780437
TI  - Effect of polycan, a beta-glucan originating from Aureobasidium, on a high-fat
      diet-induced hyperlipemic hamster model.
AB  - The aim of the present study was to analyze the effect of polycan, a beta-glucan
      originating from Aureobasidium, on high-fat diet (HFD)-induced hyperlipemia and
      hepatic damage. A total of 30 hamsters were divided into 6 groups based on their
      body weight following acclimatization: control, sham, simvastatin (SIMVA) and 3
      Polycan groups. In the polycan groups, Polycan, at three concentrations (31.25,
      62.5 and 125 mg/kg), was administered orally once a day for 56 days, in addition
      to the HFD. On the day of sacrifice, changes in the body weight, food
      consumption, liver weight and serum levels of aspartate aminotransferase (AST),
      alanine aminotransferase (ALT), low-density lipoprotein (LDL), high-density
      lipoprotein (HDL), triglyceride and total cholesterol (T-CHOL) were observed, as
      well as changes to the liver and aorta (thoracic and abdominal) histopathology
      and histomorphometry. The results from the polycan groups were compared with a
      SIMVA 10 mg/kg oral treatment group, in addition to the sham and vehicle control
      groups. After the HFD-induced hyperlipidemic hamsters were administered Polycan,
      there was no significant change in their body weight and food consumption when
      compared with the hamsters in the vehicle control group. However, the serum
      levels of AST, ALT, triglyceride, T-CHOL and LDL were significantly reduced in a
      dose-dependent manner when compared with the vehicle control group (P<0.05).
      Furthermore, the levels of liver steatosis and arteriosclerosis in the abdominal
      and thoracic aorta were significantly decreased in a dose-dependent manner
      (P<0.01). In the SIMVA-treated group, body weight (P<0.05), the serum level of
      lipids (triglyceride, T-CHOL and LDL; P<0.01) and the level of arteriosclerosis
      (P<0.01) were significantly reduced when compared with the vehicle control group.
      However, liver weight and the serum levels of AST, ALT, and liver steatosis
      increased when compared with the vehicle control group. Based on these results,
      it was concluded that polycan exerts a favorable effect in decreasing HFD-induced
      hyperlipemia and associated atherosclerosis, with relatively good protective
      effects on liver damage.

PMID- 25780438
TI  - Superficial siderosis of the central nervous system: A case report.
AB  - Superficial siderosis of the central nervous system (SSCNS) is a rare syndrome
      resulting from hemosiderin deposits in neuronal tissues close to the
      cerebrospinal fluid. SSCNS is characterized by sensorineural deafness, cerebellar
      ataxia and signs of pyramidal tract dysfunction. The present study describes a
      patient with SSCNS that did not suffer from hearing loss, which is the most
      common symptom of SSCNS. The patient was a 48-year-old male, presenting with
      dizziness, ataxia and slurred speech. The patient's ataxia was characterized by
      dizziness, nystagmus, dysarthria, abnormal finger-nose pointing and heel-knee
      shin tests and a positive Chaddock sign. The patient had suffered from a pontine
      hemorrhage two years prior to the study. Audiometric tests showed normal hearing
      during the hospital stay and at the two-month follow-up examination. The
      diagnosis of SSCNS was made based on magnetic resonance images, which showed
      areas of linear hypointensity on the surface of the pons with mild cerebellar
      atrophy. However, a long-term follow-up is required to monitor the hearing of the
      patient. Improved understanding of SSCNS is important for clinicians to identify
      SSCNS patients who present without typical clinical symptoms.

PMID- 25780439
TI  - Comparison of droplet digital PCR and conventional quantitative PCR for measuring
      EGFR gene mutation.
AB  - Early detection of epidermal growth factor receptor (EGFR) mutation, particularly
      EGFR T790M mutation, is of clinical significance. The aim of the present study
      was to compare the performances of amplification refractory mutation system-based
      quantitative polymerase chain reaction (ARMS-qPCR) and droplet digital polymerase
      chain reaction (ddPCR) approaches in the detection of EGFR mutation and explore
      the feasibility of using ddPCR in the detection of samples with low mutation
      rates. EGFR gene mutations in plasmid samples with different T790M mutation rates
      (0.1-5%) and 10 clinical samples were detected using the ARMS-qPCR and ddPCR
      approaches. The results demonstrated that the ARMS-qPCR method stably detected
      the plasmid samples (6,000 copies) with 5 and 1% mutation rates, while the ddPCR
      approach reliably detected those with 5% (398 copies), 1% (57 copies), 0.5% (24
      copies) and 0.1% (average 6 copies) mutation rates. For the 10 clinical samples,
      the results for nine samples by the ARMS-qPCR and ddPCR methods were consistent;
      however, the sample N006, indicated to be EGFR wild-type by ARMS-qPCR, was
      revealed to have a clear EGFR T790M mutation with seven copies of mutant alleles
      in a background of 6,000 wild-type copies using ddPCR technology. This study
      demonstrates the feasibility of applying the ddPCR system to detect EGFR mutation
      and identified the advantage of ddPCR in the detection of samples with a low EGFR
      mutation abundance, particularly the secondary EGFR T790M resistance mutation,
      which enables early diagnosis before acquired resistance to tyrosine kinase
      inhibitors becomes clinically detectable.

PMID- 25780440
TI  - Facial cutaneous Rosai-Dorfman disease: A case report and literature review.
AB  - Rosai-Dorfman disease (RDD), otherwise known as sinus histiocytosis with massive
      lymphadenopathy, is a rare disease. Cutaneous RDD (CRDD) is an extremely rare
      form of RDD, which is limited to the skin. The present study examined a case of
      purely CRDD in a 25-year-old female patient who presented with a two-month
      history of red plaques on her face. In addition, a review of the literature was
      conducted, where the etiology, pathology, clinical characteristics and treatment
      of the disease were discussed. From a dermatological perspective, the current
      study aimed to emphasize the histological features and clinical morphology of
      cutaneous RDD. Clinicians should have sufficient knowledge to be able to
      recognize and manage this rare condition. The present study found that the
      presence of reddish-yellow nodules on the face without any particular sensitivity
      may be useful in the diagnosis of CRDD. Treatment with topical steroids was found
      to be beneficial in alleviating CRDD.

PMID- 25780441
TI  - Prognostic value of excision repair cross-complementation group 1 expression in
      gastric cancer: A meta-analysis.
AB  - The prognostic impact of excision repair cross-complementation group 1 (ERCC1)
      expression in gastric cancer (GC) has been investigated for decades, but has
      yielded controversial results. The aim of the present study was to provide a
      precise evaluation of whether the expression levels of ERCC1 are associated with
      overall survival (OS) in patients with GC. A systematic search of Medline and
      Embase was conducted. Original studies concerning OS and ERCC1 expression were
      included for critical appraisal. A total of 15 studies comprising 1,425 patients
      with GC were identified. The results revealed that high/positive ERCC1 expression
      was an indicator of poor survival in patients with GC [hazard ratio (HR) 1.48;
      95% confidence interval (CI) 1.02-2.10; P=0.036; I2=83.8%; random-effects model]
      compared with low/negative ERCC1 expression. Subgroup analysis indicated that
      high/positive ERCC1 expression had a significant unfavorable impact on OS in the
      group of patients evaluated by reverse transcription polymerase chain reaction
      (RT-PCR; HR 2.57; 95% CI 1.49-4.45). Furthermore, high/positive ERCC1 expression
      was found to be associated with poor survival in patients receiving platinum
      based chemotherapy in the RT-PCR group (HR 2.13; 95% CI 1.06-4.27). These data
      suggest that ERCC1 may be a useful prognostic factor for GC. In addition, low
      mRNA levels of ERCC1 appear to be associated with a significant favorable OS
      benefit from platinum-based chemotherapy.

PMID- 25780442
TI  - Metformin inhibits the proliferation of A431 cells by modulating the PI3K/Akt
      signaling pathway.
AB  - The ability of metformin, an antidiabetic drug with wide applications, to inhibit
      tumor cell growth has recently been discovered. The PI3K/Akt signaling pathway
      has been found to play an important role in the survival, proliferation and
      apoptosis of tumor cells. The aim of the present study was to explore the effect
      of metformin on the proliferation of A431 human squamous cell carcinoma cells and
      the underlying molecular mechanisms. A431 cells in the logarithmic growth phase
      were treated with 0, 15, 30, 45 and 60 mM metformin for 12, 24 and 36 h,
      respectively. Cell morphology with 45 mM metformin treatment for 24 h was
      observed under a microscope. The proliferation of A431 cells was detected by the
      Cell Counting kit-8 colorimetric method. The mRNA expression levels of PI3K and
      Akt were detected by reverse transcription-polymerase chain reaction (RT-PCR).
      The protein expression levels of PI3K, Akt and phosphorylated (p)-Akt were
      detected by western blot analysis. Metformin treatment caused morphological
      change in A431 cells and inhibited their proliferation in a significant time- and
      dose-dependent manner. RT-PCR results showed that the mRNA expression of PI3K was
      inhibited by metformin in a time- and dose-dependent manner (P<0.05). However,
      there was no significant change in the mRNA expression of Akt following metformin
      treatment (P>0.05). Western blotting results showed that the protein expression
      levels of PI3K and p-Akt were inhibited by metformin in a time- and dose
      dependent manner (P<0.05). In conclusion, metformin significantly inhibited the
      proliferation of A431 cells in the current study, which may be strongly
      associated with the inhibition of the PI3K/Akt signaling pathway.

PMID- 25780443
TI  - VE/VCO2 slope and its prognostic value in patients with chronic heart failure.
AB  - The minute ventilation/carbon dioxide production (VE/VCO2) slope has been widely
      demonstrated to have strong prognostic value in patients with chronic heart
      failure (CHF), and the risk of mortality is believed to increase when the VE/VCO2
      slope is >32.8; however, there is little evidence concerning the prognostic value
      of the VE/VCO2 slope in Chinese patients. In the present study, the prognostic
      value of the VE/VCO2 slope was investigated in patients with CHF. A total of 258
      subjects underwent symptom-limited cardiopulmonary exercise testing (CPET) and
      were divided into CHF (113 males and 16 females; LVEF <0.49) and control (106
      males and 23 females) groups. The cardiac-related events over a median 33.7-month
      follow-up period subsequent to the CPET were evaluated using receiver operating
      characteristic curve analysis. The VE/VCO2 slope was significantly different
      between the CHF and control groups (P<0.001). The area under the curve (AUC) for
      the VE/VCO2 slope in predicting cardiac-related mortalities in the patients with
      CHF was 0.670 (P<0.05), and the sensitivity and specificity of the VE/VCO2 slope
      were 0.667 and 0.620, respectively. The optimal threshold of the VE/VCO2 slope
      for predicting cardiac-related mortalities in patients with CHF was >=39.3. The
      AUC for the VE/VCO2 slope in predicting cardiac-related hospitalizations in
      patients with CHF was 0.682 (P<0.05), and the sensitivity and specificity of the
      VE/VCO2 slope were 0.631 and 0.778, respectively. The optimal threshold of the
      VE/VCO2 slope for predicting cardiac-related hospitalizations in patients with
      CHF was >=32.9. In conclusion, ventilatory efficiency decreases in patients with
      CHF. The VE/VCO2 slope is a strong predictor of cardiac-related mortalities in
      the patients with CHF analyzed.

PMID- 25780444
TI  - Golgi protein 73 as a biomarker for hepatocellular carcinoma: A diagnostic meta
      analysis.
AB  - Hepatocellular carcinoma (HCC) is the most common primary malignancy of the liver
      and the third leading cause of cancer-related mortality worldwide. Conflicting
      results have been reported regarding the use of serum Golgi protein 73 (GP73) as
      a promising serum marker for the diagnosis of HCC; therefore, the aim of the
      present study was to provide a systematic review of the diagnostic performance of
      GP73 for HCC. Following a systematic review of the relevant studies, a number of
      indices associated with the accuracy of the diagnostic performance of GP73,
      including the sensitivity and specificity, were pooled using Meta Disc 1.4
      software. Data were presented as forest plots, and summary receiver operating
      characteristic (SROC) curve analysis was used to summarize the overall test
      performance. Eleven studies were included in this meta-analysis. The summary
      estimates for serum GP73 in diagnosing HCC were as follows: Sensitivity, 77% [95%
      confidence interval (CI), 75-79%]; specificity, 91% (95% CI, 90-92%); positive
      likelihood ratio, 4.34 (95% CI, 2.19-8.59); negative likelihood ratio, 0.30 (95%
      CI, 0.26-0.36) and diagnostic odds ratio, 15.78 (95% CI, 6.95-35.83). The area
      under the SROC curve was 0.8638, and the Q index was 0.7944. Significant
      heterogeneity was found. This meta-analysis indicates a moderate diagnostic value
      of GP73 in HCC; however, further studies with rigorous design, large sample size
      and multiregional cooperation are required.

PMID- 25780445
TI  - Cytotoxic effects of solvent-extracted active components of Salvia miltiorrhiza
      Bunge on human cancer cell lines.
AB  - Herbal extracts and dietary supplements may be extracted from the medicinal
      plants used in traditional Chinese medicine, and are used increasingly commonly
      worldwide for their benefits to health and quality of life. Thus, ensuring that
      they are safe for human consumption is a critical issue for the preparation of
      plant extracts as dietary supplements. The present study investigated extracts of
      Salvia miltiorrhiza Bunge (S. miltiorrhiza), traditionally used in Asian
      countries to treat a variety of conditions, as a dietary supplement or as an
      ingredient in functional foods. Dried S. miltiorrhiza root was extracted with
      various solvents and under varying extraction conditions, and the effects of the
      extracts on the viability of five human cancer cell lines were compared. Extracts
      obtained using 100% ethanol and 100% acetone as solvents exhibited more potent
      effects compared with extracts obtained using 70 and 30% aqueous ethanol.
      Furthermore, the active components of S. miltiorrhiza ethanol extracts, known as
      tanshinones, were investigated. Dihydrotanshinone I was observed to exhibit a
      higher cytotoxic potential compared with the other tanshinones in the majority of
      the examined cell lines. Conversely, cryptotanshinone exhibited weak anti-cancer
      activity. In summary, the results of the present study suggest that the active
      components obtained from an ethanol extract of S. miltiorrhiza possess the
      potential to be used as ingredients in functional and health care foods that may
      be used to improve the effectiveness of chemotherapeutics in the prevention
      and/or treatment of cancer.

PMID- 25780446
TI  - Sacral myeloid sarcoma involving multiple metastases to the brain: A case report.
AB  - The presentation of myeloid sarcoma (MS) in the bone is common; however, rarely
      does the tumor occur in the sacral spine, and in a normal patient with no history
      of acute myeloid leukemia. The present study describes the rare case of a
      previously healthy 24-year-old male patient, who presented with a history of six
      months of repeated pain in the right leg and hip and limping for less than a
      month, who was diagnosed with sacral MS. Despite receiving surgical management
      and chemotherapy promptly subsequent to the diagnosis and undergoing close
      observation following the treatment, the patient still developed metastases to
      multiple sites of the brain. Taking into account the similar presentation of this
      rare disease to other entities, the early and accurate diagnosis of MS is vital,
      and the condition should be considered as a threatening manifestation with the
      possibility of metastasis to other sites of the body.

PMID- 25780447
TI  - Treatment of chest wall tuberculosis with transdermal ultrasound-mediated drug
      delivery.
AB  - Chest wall tuberculosis (TB) is an endemic disease with a large number of
      variants. The condition affects numerous parts of the body and can penetrate the
      skin to form chronic open ulcers. Current treatment methods include oral anti-TB
      drugs and surgery. However, conventional drug treatments are not effective due to
      the difficulty in achieving an effective local concentration, and certain
      patients are unable to tolerate surgery. The recurrence rate for chest wall TB is
      high following surgery, and may result in the prolonged healing of wounds in
      certain patients, as well as chronic sinusitis and fistula formation. To identify
      a safe, simple, less invasive and more clinically effective treatment method, the
      present study investigated transdermal ultrasound-mediated anti-TB drug delivery.
      A total of 186 patients were selected and randomly divided into transdermal
      ultrasound, surgery and oral anti-TB drug only groups. Rifampicin was the drug
      delivered by transdermal ultrasound. The cure and efficiency rates were shown to
      be 87.10 and 93.55%, respectively, in the ultrasound treatment group. No
      statistically significant difference was observed in the cure rates between the
      transdermal ultrasound and surgery groups; however, a statistically significant
      difference was identified in the cure rates between the transdermal ultrasound
      and oral anti-TB drug only groups. Therefore, transdermal ultrasound technology
      was shown to deliver anti-TB drugs quickly and directly, which resulted in a high
      local concentration of the drug, overcoming the problem of obtaining an effective
      local drug concentration. The observations demonstrated that transdermal
      ultrasound-mediated drug delivery is an effective method by which to control TB,
      particularly when compared with traditional oral anti-TB therapy and surgery.

PMID- 25780448
TI  - Significance of resistin expression in acute pancreatitis.
AB  - The aim of the present study was to detect the expression of resistin in rats
      with acute pancreatitis (AP) and investigate its significance in the pathogenesis
      of AP. In total, 40 Sprague-Dawley rats were randomly divided into four groups
      (n=10), including the normal control, sham-operated, acute edematous pancreatitis
      (AEP) and acute necrotizing pancreatitis (ANP) groups. Following the
      establishment of animal models, the levels of serum resistin, C-reactive protein
      (CRP), tumor necrosis factor-alpha (TNF-alpha) and interleukin (IL)-1beta were
      measured using ELISA. Resistin expression in the pancreatic tissues was detected
      using an immunohistochemical method. In addition, the mRNA expression of resistin
      in the pancreatic tissues was analyzed with quantitative polymerase chain
      reaction. The levels of serum amylase, serum resistin, TNF-alpha, IL-1beta and
      CRP were all significantly higher in the AEP and ANP groups when compared with
      the control and sham-operated groups (P<0.01), as were the pancreas/body weight
      ratios and pathological scores of the pancreas. These increases were more
      significant in the ANP group than in the AEP group (P<0.05). The mRNA expression
      levels of resistin in the pancreatic tissues were markedly higher in the AEP and
      ANP groups when compared with the control and sham-operated groups (P<0.01),
      particularly in the pancreatic tissues of the ANP group, which exhibited notably
      higher levels compared with the AEP group. The serum resistin level was found to
      positively correlate with the serum levels of CRP, TNF-alpha and IL-1beta, and
      the pathological scores of the pancreatic tissues. In conclusion, the results
      indicated that resistin may be associated with the occurrence and development of
      AP; thus, the protein may be a valuable indicator for assessing the severity of
      AP.

PMID- 25780449
TI  - Plasma levels of tumor necrosis factor-alpha in adolescent idiopathic scoliosis
      patients serve as a predictor for the incidence of early postoperative cognitive
      dysfunction following orthopedic surgery.
AB  - The aim of the present study was to evaluate whether the levels of the plasma
      biomarkers, cortisol, interleukin (IL)-1beta, IL-6, IL-10 and tumor necrosis
      factor (TNF)-alpha, change in adolescent idiopathic scoliosis patients with
      postoperative cognitive dysfunction (POCD); thus, may serve as predictive factors
      for POCD. In total, 75 adolescent scoliosis patients, aged between 11 and 18
      years and categorized as American Society of Anesthesiologists classification I
      or II, were scheduled for orthopedic surgery with general anesthesia. Blood
      samples were collected on the day of admission and at day 2 following surgery.
      The plasma levels of IL-1beta, IL-6, IL-10 and TNF-alpha were measured using an
      enzyme-linked immunosorbent assay, while the concentrations of cortisol were
      determined using a radioimmunoassay. Cognitive function was assessed one day
      prior to and at day 7 following the surgery in a quiet room with the guidance of
      a Chinese version protocol. In total, 66 patients completed the sample collection
      and neurocognitive tests. According to the criteria for the diagnosis of POCD, 19
      patients (28.8%) developed POCD within seven days of surgery. No statistically
      significant differences were observed in the baseline concentrations of cortisol,
      TNF-alpha, IL-1beta, IL-10 or IL-6 between the POCD and non-POCD groups. However,
      the baseline plasma level of TNF-alpha on day 2 in the POCD group was found to be
      higher compared with the non-POCD group. In addition, at day 2 after surgery, the
      concentration of cortisol in the non-POCD group was higher compared with the POCD
      group. Therefore, the plasma level of TNF-alpha in adolescent idiopathic
      scoliosis patients at day 2 following orthopedic surgery may be a predictor for
      the incidence of early POCD.

PMID- 25780450
TI  - Study of genes associated with the 'anger-in' and 'anger-out' emotions of humans
      using a rat model.
AB  - The aim of the present study was to investigate the genes associated with 'anger
      in' (tendency to suppress anger) and 'anger-out' (tendency to express anger
      through verbal or physical means) emotions in humans. Wistar rats were divided
      into five groups (n=10/group), based on the type of model and the Chinese
      medicinal formulation administered, and the rat models were established. The five
      groups were as follows: Normal control (control), anger-in model (AIM), anger-in
      Jingqianshu-administered (AIA), anger-out model (AOM) and anger-out Jingqianping
      administered (AOA). Open-field, resident-intruder and aggressive behavior tests
      were carried out, as well as gene expression analysis, reverse transcription
      quantitative polymerase chain reaction and western blot analyses. The body
      weights of the rats in the AIM and AOM groups were significantly lower than those
      of the control group rats. The open-field test indicated that the scores in the
      AOM group were significantly higher (P<0.05) than those in the AIM group. The
      aggression scores of the rats in the AOM group were significantly higher than
      those of the AIM group rats. Jingqianshu and Jingqianping granules attenuated the
      behavioral changes of the rats. 5-Htr2C, GABABR2 and 5-Htr3B were associated with
      anger-in and anger-out emotions. Jingqianping and Jingqianshu granules attenuated
      the changes in the mRNA expression of 5-Htr2C, GABABR2 and 5-Htr3B, as indicated
      by RT-qPCR, and showed similar effects on protein expression, as demonstrated by
      western blot analysis. The present study demonstrated that the anger-in and anger
      out emotions of rats are closely associated with 5-Htr2C, GABABR2 and 5-Htr3B
      genes, and that Jingqianshu and Jingqianping granules attenuate the abnormal
      behaviors of model rats. These findings may be useful for the treatment of
      emotional disorders associated with anger.

PMID- 25780451
TI  - Expression of Toll-like receptors in the mucosa of patients with ulcerative
      colitis.
AB  - Patients with ulcerative colitis (UC) have a high risk of developing colorectal
      cancer. The aim of the present study was to evaluate the expression pattern of
      Toll-like receptors (TLRs) in the colonic mucosa of patients with UC. Colonic
      mucosal biopsy specimens were collected during colonoscopy from 30 patients with
      UC and 30 patients with normal findings as controls. The protein and mRNA
      expression levels of TLRs 1-4 and TLR9 were measured by immunohistochemistry and
      reverse transcription-quantitative polymerase chain reaction analysis,
      respectively. The results showed that the mRNA and protein expression of TLR2,
      TLR4 and TLR9, but not TLR1 and TLR3, was significantly increased in the colonic
      mucosa of patients with UC compared with that in the normal controls. TLR (TLR2,
      TLR4 and TLR9) immunoreactivity was found in the cytoplasm of epithelial cells in
      the mucosa, and occasionally in the endothelium of small vessels of the stromal
      tissues. In conclusion, TLR2, TLR4 and TLR9 expression may be important in the
      biological pathogenesis of UC. TLR alterations in the innate response system may
      contribute to the pathogenesis of UC.

PMID- 25780452
TI  - Knockdown of S100A11 expression suppresses ovarian cancer cell growth and
      invasion.
AB  - As a member of the S100 protein family, S100A11 expression is often upregulated
      in human cancer tissues. Numerous studies have demonstrated that S100A11 plays an
      important role in the progression of cancer. However, the function of S100A11 in
      ovarian cancer remains elusive. In the present study, the expression levels of
      S100A11 were found to be significantly increased in ovarian cancer cells.
      Subsequently, the expression of S100A11 in ovarian cancer HO8910 cells was
      knocked down using short hairpin (sh)RNA in order to investigate the biological
      effects of S100A11 on the progression of the disease. The results demonstrated
      that knockdown of S100A11 by shRNA inhibited the proliferation, anchorage
      independent growth, invasion and migration of HO8910 cells. In addition,
      knockdown of S100A11 increased the expression of E-cadherin and decreased the
      expression of Snail in HO8910 cells. Collectively, these results indicated that
      S100A11 was able to promote the growth, invasion and migration of ovarian cancer
      cells. Therefore, S100A11 may serve as a potential molecular target for the
      diagnosis and treatment of ovarian cancer.

PMID- 25780453
TI  - Preconditioning with cobalt chloride modifies pain perception in mice.
AB  - Cobalt chloride (CoCl2) modifies mitochondrial permeability and has a hypoxic
      mimetic effect; thus, the compound induces tolerance to ischemia and increases
      resistance to a number of injury types. The aim of the present study was to
      investigate the effects of CoCl2 hypoxic preconditioning for three weeks on
      thermonociception, somatic and visceral inflammatory pain, locomotor activity and
      coordination in mice. A significant pronociceptive effect was observed in the hot
      plate and tail flick tests after one and two weeks of CoCl2 administration,
      respectively (P<0.001). Thermal hyperalgesia (Plantar test) was present in the
      first week, but recovered by the end of the experiment. Contrary to the
      hyperalgesic effect on thermonociception, CoCl2 hypoxic preconditioning decreased
      the time spent grooming the affected area in the second phase of the formalin
      test on the orofacial and paw models. The first phase of formalin-induced pain
      and the writhing test were not affected by CoCl2 preconditioning. Thus, the
      present study demonstrated that CoCl2 preconditioning has a dual effect on pain,
      and these effects should be taken into account along with the better-known neuro
      , cardio- and renoprotective effects of CoCl2.

PMID- 25780454
TI  - Curcumin improves the paclitaxel-induced apoptosis of HPV-positive human cervical
      cancer cells via the NF-kappaB-p53-caspase-3 pathway.
AB  - Paclitaxel, isolated from Taxus brevifolia, is considered to be an efficacious
      agent against a wide spectrum of human cancers, including human cervical cancer.
      However, dose-limiting toxicity and high cost limit its clinical application.
      Curcumin, a nontoxic food additive, has been reported to improve paclitaxel
      chemotherapy in mouse models of cervical cancer. However, the underlying
      mechanisms remain unclear. In this study, two human cervical cancer cell lines,
      CaSki [human papilloma virus (HPV)16-positive] and HeLa (HPV18-positive), were
      selected in which to investigate the effect of curcumin on the anticancer action
      of paclitaxel and further clarify the mechanisms. Flow cytometry and MTT analysis
      demonstrated that curcumin significantly promoted paclitaxel-induced apoptosis
      and cytotoxicity in the two cervical cell lines compared with that observed with
      paclitaxel alone (P<0.05). Reverse transcription-polymerase chain reaction
      indicated that the decline of HPV E6 and E7 gene expression induced by paclitaxel
      was also assisted by curcumin. The expression levels of p53 protein and cleaved
      caspase-3 were increased significantly in the curcumin plus paclitaxel-treated
      HeLa and CaSki cells compared with those in the cells treated with paclitaxel
      alone (P<0.01). Significant reductions in the levels of phosphorylation of
      IkappaBalpha and the p65-NF-kappaB subunit in CaSki cells treated with curcumin
      and paclitaxel were observed compared with those in cells treated with paclitaxel
      alone (P<0.05). This suggests that the combined effect of curcumin and paclitaxel
      was associated with the NF-kappaB-p53-caspase-3 pathway. In conclusion, curcumin
      has the ability to improve the paclitaxel-induced apoptosis of HPV-positive human
      cervical cancer cell lines via the NF-kappaB-p53-caspase-3 pathway. Curcumin in
      combination with paclitaxel may provide a superior therapeutic effect on human
      cervical cancer.

PMID- 25780455
TI  - Effective components of Panax quinquefolius and Corydalis tuber protect the
      myocardium by inhibiting platelet activation and improving the hypercoagulable
      state.
AB  - The aim of the present study was to investigate the effects of extract of Panax
      quinquefolius and Corydalis tuber (EPC) on platelet activation and the
      hypercoagulable state in rats with acute myocardial infarction (AMI). The MI
      model in Wistar rats was induced by coronary artery ligation. Sham surgery was
      performed as a control. The surviving rats that underwent MI surgery were divided
      into control (administered normal saline), metoprolol (9 mg/kg) and low-,
      moderate- and high-dose EPC groups (0.54, 1.08 g/kg and 2.16 g/kg, respectively).
      Saline, metoprolol and EPC were administered by gastrogavage for two consecutive
      weeks. The morphological changes of the myocardium were assessed by hematoxylin
      and eosin and nitroblue tetrazolium staining. Serum von Willebrand factor (vWF),
      D-dimer (DD), platelet membrane glycoproteins IIb-IIIa (GPIIb-IIIa) and CD62P
      levels were assessed using enzyme-linked immunosorbent assay. EPC attenuated the
      pathological changes of the myocardium. High-dose EPC decreased the serum
      concentration of vWF when compared with control group. Moderate and high doses of
      EPC decreased the DD and GPIIb-IIIa levels, and the CD62P level was gradually
      decreased with EPC dose escalation. The results therefore demonstrated that EPC
      protects the myocardium by inhibiting platelet activation and improving the
      hypercoagulable state in a rat model of AMI.

PMID- 25780456
TI  - Construction of tissue-engineered laryngeal cartilage with a hollow, semi-flared
      shape using poly(3-hydroxybutyrate-co-3-hydroxyhexanoate) as a scaffold.
AB  - The aim of the present study was to construct tissue-engineered laryngeal
      cartilage with a hollow, semi-flared shape using a poly(3-hydroxybutyrate-co-3
      hydroxyhexanoate) (PHBHH) scaffold. Porous PHBHH was prepared and formed into a
      hollow, semi-flared shape, and the cell-material composites were cultured for one
      week in vitro prior to implantation in vivo. Cells of the nine rabbits of the
      experimental group were filled and encapsulated in the myofascial flap-shaping
      material composite for in situ implantation. The three rabbits in the control
      group were treated with the shaping material without the chondrocytes. Cartilage
      regeneration was assessed at six, 12 and 18 weeks after surgery. In the
      experimental group, the shape and porosity of the material were ideal, the cells
      exhibited good adhesion with the material and the myofascial flap blood supply
      was rich. The engineered laryngeal cartilage with the hollow, semi-flared shape
      was ideally formed, and the cartilage formed at six weeks after the surgery.
      Further maturation of the cartilage was observed at 12 and 18 weeks after the
      surgery. PHBHH was a suitable material for the formation of a hollow, semi-flared
      shape with good cellular compatibility. Myofascial flap filling and wrapping can
      be used to build tissue-engineered laryngeal cartilage with a hollow, semi-flared
      shape.

PMID- 25780457
TI  - Effects of vitamins E and C combined with beta-carotene on cognitive function in
      the elderly.
AB  - The aim of the present study was to investigate the effect of vitamins E (VE) and
      C (VC), combined with beta-carotene (beta-C), on cognitive function in the
      elderly. A total of 276 elderly subjects completed the prospective study
      following treatment with VE, VC and different doses of beta-C or with VE only.
      Cognitive function was assessed by the Mini-Mental State Examination (MMSE) and
      Hasegawa Dementia Scale (HDS) tests. The plasma levels of amyloid-beta (Abeta)
      and estradiol (E2) were determined by radioimmunoassay (RIA). Results from the
      MMSE and HDS assessments indicated that the treatment strategy of VE and VC
      combined with beta-C significantly improved cognitive function in the elderly
      subjects, particularly with higher doses of beta-C. Furthermore, RIA suggested
      that treatment with these vitamins could markedly reduce plasma Abeta levels and
      elevate plasma E2 levels. The present findings suggest that treatment with VE, VC
      and beta-C results in promising improvements in cognitive function in the
      elderly.

PMID- 25780458
TI  - Effects of fentanyl, midazolam and their combination on immune function and
      mortality in mice with sepsis.
AB  - The aim of this study was to investigate the effects of fentanyl and/or midazolam
      on the immune function and mortality of septic mice. Mice were randomly divided
      into sham-operated, model, fentanyl-, midazolam- and combination-treated groups.
      The body weights and locomotor activities of the mice were measured, prior to and
      following surgery, and the mortality rates following surgery were recorded and
      compared among these groups. The organ weights and the corresponding coefficients
      were measured and calculated. Leukocyte numbers in peritoneal and thoracic cavity
      lavage fluid were counted, and the serum levels of the inflammation-related
      cytokines interleukin (IL)-1beta, IL-10, tumor necrosis factor (TNF)-alpha,
      procalcitonin (PCT) and C-reactive protein (CRP) were detected by enzyme-linked
      immunosorbent assay (ELISA). The results demonstrated that the locomotor
      activities were reduced in septic mice, and medication led to significant
      declined body weights in these model animals. Importantly, the mortality rates of
      the septic mice were reduced by fentanyl and/or midazolam, and the
      histopathological changes were influenced by the medication. Moreover, in the
      medication-treated groups, the leukocyte numbers in the peritoneal cavity lavage
      fluid were lower than those in the model group, while the medication slightly
      increased the numbers of leukocytes in the thoracic cavity lavage fluid. ELISA
      indicated that the levels of proinflammatory cytokines were reduced by fentanyl
      and/or midazolam, which may contribute to the beneficial effects of these
      medications in septic mice. Analgesic and/or sedative drugs could reduce
      inflammatory responses in septic mice, and immunosedation may have contributed to
      the improved mortality rates in these models. These results provide a theoretical
      basis for further clinical studies concerning the treatment of sepsis with these
      medications.

PMID- 25780459
TI  - Impact of ankylosing spondylitis on sexual function: A systematic review and meta
      analysis.
AB  - A number of studies have reported the association of sexual problems with
      ankylosing spondylitis (AS); however, the results have been conflicting. The
      present study aimed to investigate the impact of AS on sexual function. To
      develop a more comprehensive understanding of sexual function in patients with
      AS, a systematic review and meta-analysis of the literature up to 2013 was
      conducted. Studies that assessed the impact of AS on sexual function by adopting
      the International Index of Erectile Function or the Female Sexual Function Index
      (FSFI) scoring system were included. Statistical analysis was performed using
      Review Manager statistical software (version 5.2). The weighted mean differences
      were calculated by employing a fixed or random effects model. A total of 484
      cases from five studies were identified as being well-documented and included in
      the meta-analysis. Compared with healthy controls, male patients with AS have a
      significant reduction in sexual function scores of erectile function (-3.07),
      orgasmic function (-1.17), sexual drive (-0.72) and intercourse satisfaction (
      1.89). Female patients with AS have a lower FSFI score in domains of desire (
      0.34) and arousal (-0.87). In conclusion, AS has a certain impact on the sexual
      function of male patients. AS appears to have a greater influence on the sexual
      function of males compared with that of females. However, the mechanism by which
      AS affects sexual function requires further evaluation by further studies of a
      larger population of patients.

PMID- 25780460
TI  - Association between red cell distribution width and the risk of heart events in
      patients with coronary artery disease.
AB  - Red cell distribution width (RDW) has been found to be a novel prognostic
      biomarker in patients with coronary artery disease (CAD); however, the
      association between RDW and the risk of heart events in patients with CAD is yet
      to be fully elucidated. Thus, the aim of the present study was to determine
      whether an elevated RDW was associated with the Framingham risk score (FRS) in
      patients with CAD. Data were retrospectively collected from Affiliated Dongyang
      Hospital of Wenzhou Medical University (Dongyang, China). The patients had
      undergone a coronary angiography and their clinical data were integrated. The
      patients (male, 260; female, 132) were divided into two groups based on the
      results of the coronary angiography, namely the CAD (n=283) and control groups
      (n=109). The FRS was calculated for all the subjects, and complete blood count
      testing with biochemical measurements was performed. The mean RDW level was
      13.7+/-1.8% in the CAD group and 13.1+/-1.0% in the control group, while the mean
      FRS was 9.0+/-4.9 in the CAD group and 6.4+/-3.9 in the control group. The RDW
      and FRS were significantly higher in the CAD group compared with the control
      group (P<0.001). No statistically significant differences were observed between
      the groups with regard to the hematocrit, mean corpuscular volume, platelets,
      glucose, urea, albumin, aspartate aminotransferase, total cholesterol,
      triglycerides (TG), high-density lipoprotein cholesterol, low-density lipoprotein
      cholesterol and N-terminal pro-brain natriuretic peptide (P>0.05). The RDW was
      shown to significantly correlate with the red blood cell (RBC) count (r=-0.133,
      P=0.029), hemoglobin level (r=-0.207, P=0.001) and TG level (r=0.226, P<0.001)
      within the laboratory parameters, as well as the FRS (r=0.206, P<0.001). In the
      stepwise multivariate linear regression, which included the RBC count, hemoglobin
      level, TG level and RDW, the FRS was predicted by hemoglobin (r2=0.034, P=0.001),
      TG (r2=0.059, P<0.001) and RDW (r2=0.030, P=0.003) parameters. Therefore, a novel
      association was revealed between higher levels of RDW and an elevated FRS in
      patients with CAD, which raises the possibility that a simple marker, RDW, may be
      associated with an increased risk of heart events in CAD patients.

PMID- 25780461
TI  - Marchiafava-Bignami disease with rare etiology: A case report.
AB  - A male, 62-year-old patient was admitted to hospital due to dizziness and gait
      disturbance for 10 days. The patient had fallen a few times due to the gait
      instability, which was associated with stiffness and memory loss. The patient had
      undergone cardiac carcinoma surgery three years previously and had no drinking
      history. Physical examination revealed that the patient was lucid when conscious
      but exhibited slurred speech, apathy and cognitive impairment. The finger-to-nose
      and rapid alternating movement tests showed the patient to be slightly clumsy.
      Magnetic resonance imaging revealed symmetric abnormal signals in the splenium of
      the corpus callosum, and the diagnosis was Marchiafava-Bignami disease (MBD). The
      patient recovered following the administration of vitamin B and other treatments.
      The patient had long-term appetite loss. A brain myelin metabolism disorder
      caused by long-term malnutrition and leading to demyelinating changes in the
      brain may have been the cause of the MBD of this patient. Clinicians should
      increase awareness of this disease and should not ignore the diagnosis of it,
      even when the patient lacks a drinking history. Early diagnosis and treatment can
      improve the prognosis of the patient.

PMID- 25780462
TI  - Doxapram hastens the recovery following total intravenous anesthesia with
      dexmedetomidine, propofol and remifentanil.
AB  - Dexmedetomidine is a suitable sedative for awake fiberoptic intubation in
      patients with obstructive sleep apnea (OSA). However, previous studies have shown
      that dexmedetomidine delays recovery from propofol-remifentanil anesthesia. This
      study aimed to determine whether doxapram may hasten the recovery following
      dexmedotomidine-propofol-remifentanil anesthesia. Sixty patients scheduled for
      uvulopalatopharyngoplasty with total intravenous anesthesia were randomized to
      two groups according to the medicine given at the end of surgery. These were the
      doxapram (1 mg/kg) and control (normal saline) groups (n=30 per group). The
      primary outcome was the time to eye opening on verbal command. The time to return
      to spontaneous breathing, to hand squeezing in response to verbal command, to
      extubation of the trachea, and the heart rate (HR), bispectral index (BIS)
      values, respiratory rate (RR) and pulse oximetry values were also recorded and
      compared. The time to return to spontaneous breathing (5.2+/-2.9 vs. 11.7+/-3.4
      min, P<0.001), eye opening (9.3+/-4.7 vs. 15.9+/-6.3 min, P<0.001), hand squeeze
      to command (11.8+/-6.5 vs. 17.6+/-7.7 min, P=0.0026) and extubation (14.2+/-7.8
      vs. 19.2+/-9.6 min, P=0.0308) were significantly shorter in the doxapram group
      compared with the control group. BIS scores (at 3-14 min), RR (at 4-10 min) and
      HR (at 2-13 min) were significantly higher in the doxapram group compared with
      those in the control group (P<0.05). Doxapram hastens the recovery from
      dexmedetomidine-propofol-remifentanil anesthesia in patients undergoing
      uvulopalatopharyngoplasty, and may benefit patients with OSA.

PMID- 25780463
TI  - Serum levels of specific IgE to Staphylococcus aureus enterotoxins in patients
      with chronic rhinosinusitis.
AB  - The aim of this study was to determine the prevalence of Staphylococcus aureus
      enterotoxins (SEs) in the serum from patients with chronic rhinosinusitis (CRS)
      and its involvement in the condition. Thirty CRS patients without nasal polyps
      (CRSsNP), 40 CRS patients with nasal polyps (CRSwNP), and 30 healthy controls
      were enrolled in this study. Peripheral blood was obtained and analyzed to
      measure the serum levels of total IgE, specific IgE to SEA, SEB and SEC, and
      eosinophil cationic protein (ECP) using ImmunoCAP assays. The positive rate and
      level of serum specific IgE to SEB, but not to SEA or SEC, were significantly
      higher in CRSwNP patients compared with the controls (P=0.027 and P=0.021,
      respectively). No significant differences were found between CRSsNP patients and
      controls, or between CRSsNP and CRSwNP patients. Serum total IgE was
      significantly elevated and positively correlated with SEB-specific IgE in the
      CRSsNP (P<0.001; r=0.393, P=0.032) and CRSwNP (P<0.001; r=0.581, P<0.001) groups.
      ECP was also significantly increased in the CRSsNP (P=0.002) and CRSwNP (P<0.001)
      groups, but not correlated with specific IgE to SEs in either CRS group. The
      results suggest that SEB may play a role in the pathogenesis of CRSwNP.

PMID- 25780464
TI  - Efficacy and safety of sitagliptin compared with sulfonylurea therapy in patients
      with type 2 diabetes showing inadequately controlled glycosylated hemoglobin with
      metformin monotherapy: A meta-analysis.
AB  - Previous randomized controlled trials (RCTs) have reported conflicting results
      for the efficacy of sitagliptin and sulfonylurea therapy in patients with type 2
      diabetes mellitus showing inadequate glycemic control with metformin monotherapy.
      To clarify these findings, a meta-analysis was conducted of the outcomes of all
      published RCTs comparing sitagliptin with sulfonylureas in the treatment of type
      2 diabetes mellitus. Standard medical databases were searched to identify
      relevant English- and Chinese-language RCTs. RCT results were compared regarding
      the mean change in glycated hemoglobin (HbA1c) level; the proportion achieving
      <7% HbAlc; and a change in body weight. No significant differences were found
      between the metformin plus sitagliptin and metformin plus sulfonylurea groups
      regarding HbAlc or the proportion achieving <7% HbAlc, while the metformin plus
      sitagliptin group experienced fewer hypoglycemic events (P<0.00001) and a greater
      reduction in body weight (P<0.00001). Metformin plus sitagliptin therapy may
      decrease HbAlc values in patients with type 2 diabetes mellitus who are not
      achieving their glycemic targets with metformin monotherapy in a manner similar
      to metformin plus sulfonylurea therapy, whilst posing a lower risk of
      hypoglycemia, and yielding a more beneficial effect on body weight.

PMID- 25780465
TI  - Role of high-mobility group box-1 in myocardial ischemia/reperfusion injury and
      the effect of ethyl pyruvate.
AB  - High-mobility group box-1 (HMGB1) acts as a proinflammatory cytokine that
      triggers and amplifies the inflammation cascade following ischemia/reperfusion
      (I/R). Ethyl pyruvate (EP) has been reported to inhibit HMGB1 release in several
      I/R models. This study was designed to investigate the potential role of HMGB1 in
      a rat myocardial I/R model and to determine the effect of EP. Male Sprague Dawley
      rats were subjected to 30 min myocardial ischemia and 48 h reperfusion. In
      protocol 1, the rats were assigned to one of four groups (n=16 per group):
      Phosphate-buffered saline (PBS) or recombinant human HMGB1 (rhHMGB1) at three
      different doses (1, 10 or 100 MUg/kg). In protocol 2, the rats were also assigned
      to one of four groups (n=16 per group): Sham, control, EP and EP + rhHMGB1. EP
      (40 mg/kg) or rhHMGB1 (100 MUg/kg) was injected intravenously prior to
      reperfusion. Hemodynamic measurements were performed, and myocardial infarct size
      (IS) was calculated. Western blotting was conducted to evaluate HMGB1, tumor
      necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) expression levels. In
      the protocol 1 rats, the IS was markedly increased in the rhHMGB1 (100 MUg/kg)
      group compared with that in the PBS group, and this increase was accompanied by
      elevated levels of TNF-alpha and IL-6. In the protocol 2 rats, I/R resulted a 4.8
      fold increase in HMGB1 expression with an increased IS and impaired cardiac
      function compared with the sham group. EP significantly inhibited the elevated
      HMGB1 level, suppressed the activated TNF-alpha and IL-6 and reduced cardiac
      dysfunction. This cardioprotection was abolished by rhHMGB1. In conclusion,
      accumulation of HMGB1 is deleterious to the heart following myocardial I/R. EP
      can exert a strong protective effect against myocardial I/R injury, and these
      benefits are associated with a reduction in HMGB1.

PMID- 25780466
TI  - Anesthetic management for resection of para-aortic paraganglioma and unexpected
      aortic resection: A case report.
AB  - Paragangliomas account for 15-20% of pheochromocytomas derived from chromaffin
      cells and secretes catecholamines. It has a high mortality rate due to
      hypertension and challenging anesthetic management. The present report is of a
      case of the successful management of paraganglioma resection with unexpected
      aortic resection. The patient presented for paraganglioma resection. The blood
      pressure (BP) was well controlled with alpha blockade followed by beta blockade
      prior to surgery. The patient was under general anesthesia, with multiple
      intravenous lines, catheters and an arterial line. Induction was achieved by the
      administration of narcotic and volatile agents. During the procedure, the aorta
      was found to require resection in order to complete the tumor resection. The BP
      changed markedly with clamping and unclamping, tumor vein ligation and tumor
      resection. The increased BP due to catecholamine release and unclamping was
      controlled with phentolamine, nitroprusside, esmolol and labetolol. Drops in BP
      due to tumor vein ligation and clamping were managed with norepinephrine and
      vasopressin. With close communication and monitoring, the surgery on the patient
      was successfully completed and the patient was discharged days later in a
      hemodynamically stable condition. The diagnosis was further confirmed by
      pathology. This was a challenging case of paraganglioma resection with unexpected
      aortic resection. The success achieved suggests that the resection of
      paraganglioma and an aortic segment requires delicate anesthetic management. The
      key are alpha blockade and beta blockade as necessary to control BP pre
      operatively, frequent communication between the anesthesiologist and surgeons,
      intra-operative intervention in excess catecholamine release with phentolamine,
      nitroprusside and labetalol prior to tumor removal, and vasopressin for
      catecholamine deficiency when clamping or subsequent to tumor removal. It is a
      delicately orchestrated process requiring team work.

PMID- 25780467
TI  - Clinical performance of biodegradable versus permanent polymer drug-eluting
      stents: A meta-analysis of randomized clinical trials at long-term follow-up.
AB  - Several types of biodegradable polymer drug-eluting stents (BPDES) have been used
      for percutaneous transluminal angioplasty; however, the safety and efficiency of
      these BPDES have not been fully evaluated. A meta-analysis was, therefore,
      conducted to compare the clinical performance of BPDES with that of permanent
      polymer drug-eluting stents (PPDES) in unselected patients with coronary
      stenosis. PubMed, Web of Science, Medline and The Cochrane Library were searched
      for randomized clinical trials (RCTs) from January 2005 to January 2014. Trials
      that compared BPDES with PPDES in patients with coronary stenosis were
      considered. Twelve RCTs with a total of 15,938 patients with coronary stenosis
      were included in this meta-analysis. No significant difference was found between
      the two arms in the incidence of major adverse cardiac events (MACE) and definite
      or probable stent thrombosis (DpST) at the one-year follow-up (P>0.10). The use
      of BPDES, however, showed a tendency towards a lower risk of MACE (P=0.09) and a
      beneficial effect by reducing DpST episodes (P=0.04) at long-term follow-up,
      particularly when compared with the incidence of DpST at the one-year follow-up.
      BPDES also tended to be associated with a decreased late lumen loss in patients
      with coronary stenosis [instrumental variable =-0.04; 95% confidence interval =
      0.08-0.00; P=0.05). In conclusion, the one-year outcomes following drug-eluting
      stent implantation showed BPDES were noninferior to PPDES in unselected patients
      with coronary stenosis. Long-term clinical outcomes, however, indicated that
      BPDES appeared to a present a lower risk of MACE and DpST.

PMID- 25780469
TI  - Welcome to the March 2015 Issue of the IJTMB.

PMID- 25780470
TI  - The impact of the Swedish massage on the kinesthetic differentiation in healthy
      individuals.
AB  - BACKGROUND: Swedish massage is one of the common treatments to provide optimal
      start and readiness of athletes. The ability of kinesthetic differentiation (KD)
      is crucial in sport performance. This skill allows to adapt demanded muscle
      forces to optimize the motor tasks, and it is responsible for the precision. In
      the literature, there is no evidence how Swedish massage influences the
      kinesthetic differentiation. PURPOSE: The objective of the study was to evaluate
      the impact of Swedish massage on the kinesthetic differentiation and muscle
      strength of hand grip. METHODS: Thirty participants took part in this
      investigation (17 women and 13 men). The assessment consisted of KD tests
      conducted on the dominant (DH) and nondominant hand (NDH) after 15 minutes of
      hand and forearm Swedish massage. The procedure consisted of 13 trials for each
      extremity. The first three were done for 100% of the participants' capabilities
      (Fmax), the next five trials were done using 50% of maximum force (50% of Fmax),
      and in the last five trials, the participants tried to use only 50% of their
      previous force (1/2 of 50%). Finally, the absolute force production error (FPE)
      was calculated for 50% (FPE_50%) and 25% (FPE_25%). RESULTS: The two-way repeated
      measure analysis of variance ANOVA did not reveal any statistically significant
      changes in maximal strength grip and KD between pre- and postmassage intervention
      in both DH and NDH hand. Correlations showed strong relationship between pre- and
      postmassage for maximum force (r = 0.92, p = .01 for DH, and r = 0.94, p = .01
      for NDH), and only for the FPE_50% (r = 0.67, p = .01 for DH, and r = 0.71, p =
      .01 for NDH). CONCLUSIONS: The results obtained indicated that the application of
      the Swedish massage did not affect the kinesthetic differentiation in this
      particular young adult group.

PMID- 25780468
TI  - Prevalence and predictors of germline CDKN2A mutations for melanoma cases from
      Australia, Spain and the United Kingdom.
AB  - BACKGROUND: Mutations in the CDKN2A and CDK4 genes predispose to melanoma. From
      three case-control studies of cutaneous melanoma, we estimated the prevalence and
      predictors of these mutations for people from regions with widely differing
      latitudes and melanoma incidence. METHODS: Population-based cases and controls
      from the United Kingdom (1586 cases, 499 controls) and Australia (596 early-onset
      cases, 476 controls), and a hospital-based series from Spain (747 cases, 109
      controls), were screened for variants in all exons of CDKN2A and the p16INK4A
      binding domain of CDK4. RESULTS: The prevalence of mutations for people with
      melanoma was similar across regions: 2.3%, 2.5% and 2.0% for Australia, Spain and
      the United Kingdom respectively. The strongest predictors of carrying a mutation
      were having multiple primaries (odds ratio (OR) = 5.4, 95% confidence interval
      (CI: 2.5, 11.6) for 2 primaries and OR = 32.4 (95% CI: 14.7, 71.2) for 3 or more
      compared with 1 primary only); and family history (OR = 3.8; 95% CI:1.89, 7.5)
      for 1 affected first- or second-degree relative and OR = 23.2 (95% CI: 11.3,
      47.6) for 2 or more compared with no affected relatives). Only 1.1% of melanoma
      cases with neither a family history nor multiple primaries had mutations.
      CONCLUSIONS: There is a low probability (<2%) of detecting a germline CDKN2A
      mutation in people with melanoma except for those with a strong family history of
      melanoma (>=2 affected relatives, 25%), three or more primary melanomas (29%), or
      more than one primary melanoma who also have other affected relatives (27%).

PMID- 25780471
TI  - Massage Impact on Pain in Opioid-dependent Patients in Substance Use Treatment.
AB  - BACKGROUND: Chronic pain is a common cause of health care utilization and high
      levels of pain are pronounced in individuals engaged in methadone maintenance
      treatment. Although massage has been demonstrated to alleviate chronic pain
      symptoms, its use as an adjunctive therapy to modify pain during opioid
      replacement treatment is absent from the literature. PURPOSE: To consider the
      efficacy of Swedish massage in reducing pain in opioid-dependent patients with
      chronic pain receiving methadone treatment. SETTING: Trial was conducted at a
      nonprofit methadone treatment center serving low-income patients. RESEARCH
      DESIGN: A randomized clinical trial with randomized to either 1) massage plus
      treatment-as-usual (TAU) (n = 27) or 2) TAU (n = 24). Durability of treatment
      effect was evaluated at Week 12. INTERVENTION: Eight weekly 50-minute Swedish
      massage sessions plus TAU or TAU alone. MAIN OUTCOME MEASURES: Pain, anxiety,
      depression, physical functioning, decreased substance use, and improvement in
      treatment engagement. RESULTS: Randomized participants were comparable at
      Baseline for demographic, pain, physical, and emotional variables. Massage group
      reported improved pain scores; worst pain had a clinically significant 2-point
      improvement while the other pain scores did not. Overall improvements were not
      observed in treatment engagement or levels of anxiety, depression, or physical
      functioning. A subgroup of the participants, who felt they could be pain-free,
      consistently reported improvements in pain from Baseline to Week 8, and this was
      most pronounced and clinically significant in the massage group. CONCLUSIONS:
      These preliminary findings do not support an overall clinically significant
      positive effect of Swedish massage on reduction in pain ratings or improvement in
      anxiety, depression, or treatment engagement in a substance-using, opioid
      dependent population with chronic pain. Future nonpharmacologic pain research in
      marginalized substance-using populations may wish to consider some of the
      challenges and limitations faced in this project.

PMID- 25780472
TI  - Development of a Hospital-based Massage Therapy Course at an Academic Medical
      Center.
AB  - BACKGROUND: Massage therapy is offered increasingly in US medical facilities.
      Although the United States has many massage schools, their education differs,
      along with licensure and standards. As massage therapy in hospitals expands and
      proves its value, massage therapists need increased training and skills in
      working with patients who have various complex medical concerns, to provide safe
      and effective treatment. These services for hospitalized patients can impact
      patient experience substantially and provide additional treatment options for
      pain and anxiety, among other symptoms. The present article summarizes the
      initial development and description of a hospital-based massage therapy course at
      a Midwest medical center. METHODS: A hospital-based massage therapy course was
      developed on the basis of clinical experience and knowledge from massage
      therapists working in the complex medical environment. This massage therapy
      course had three components in its educational experience: online learning,
      classroom study, and a 25-hr shadowing experience. The in-classroom study portion
      included an entire day in the simulation center. RESULTS: The hospital-based
      massage therapy course addressed the educational needs of therapists
      transitioning to work with interdisciplinary medical teams and with patients who
      have complicated medical conditions. Feedback from students in the course
      indicated key learning opportunities and additional content that are needed to
      address the knowledge and skills necessary when providing massage therapy in a
      complex medical environment. CONCLUSIONS: The complexity of care in medical
      settings is increasing while the length of hospital stay is decreasing. For this
      reason, massage provided in the hospital requires more specialized training to
      work in these environments. This course provides an example initial step in how
      to address some of the educational needs of therapists who are transitioning to
      working in the complex medical environment.

PMID- 25780473
TI  - Lateral knee pain requires a thorough assessment and adequate, best-practice
      intervention.

PMID- 25780474
TI  - In response: Lateral Knee Pain Requires a Thorough Assessment and Adequate, Best
      Practice Intervention.

PMID- 25780475
TI  - A Systematic Review and Meta-Analysis of Open vs. Laparoscopic Resection of
      Gastric Gastrointestinal Stromal Tumors.
AB  - Gastric gastrointestinal stromal tumors (GISTs) are the most common sarcoma of
      the gastrointestinal tract, and surgical resection is the primary treatment of
      early disease. Limited data exist concerning laparoscopic resections of these
      neoplasms. This systematic review was designed to evaluate the literature
      comparing laparoscopic and open surgical resection of gastric GISTs and to assess
      the effectiveness and safety of this minimally invasive technique. We performed a
      systematic search of MEDLINE, the Cochrane Library, PubMed, Embase, Scopus, Web
      of Science, Google Scholar, the clinical trials database and ProQuest
      Dissertations and Theses as well as the past 3 years of conference abstracts from
      the Society of American Gastrointestinal and Endoscopic Surgeons Annual Meetings.
      Studies comparing the open and the laparoscopic approaches to the resection of
      gastric GISTs were included in this systematic review. Two reviewers
      independently performed the screen of titles and abstracts, the full manuscript
      review, the data extraction and the risk of bias assessment. A quantitative
      analysis was performed. Of the 189 studies identified, seven studies were
      included. The laparoscopic approach was associated with a significantly lower
      length of hospital stay (3.82 days (2.14 - 5.49)). There was no observed
      difference in operative time, adverse events, estimated blood loss, overall
      survival and recurrence rates. This study supports that laparoscopic resection is
      safe and effective for gastric GISTs and is associated with a significantly lower
      length of hospital stay. Further trials are needed for cost analysis and to
      rigorously assess oncologic outcomes. 

PMID- 25780476
TI  - Small vessel disease/white matter disease of the brain and its association with
      osteoporosis.
AB  - BACKGROUND: Evidence now suggests the role of neural effect on bone mass control.
      The effect of small vessel disease of the brain on osteoporosis has not been
      studied. The aim of this study was to investigate the association of white matter
      disease (WMD) of the brain with osteoporosis in the elderly. METHODS: In this
      retrospective cross-sectional study, 780 consecutive patient charts between 2010
      and 2011 were reviewed in the Senior's Outpatient Clinic at the University of
      Alberta Hospital. Subjects with brain computerized tomography (CT) were included
      in the study. Subjects with incomplete information, intracranial hemorrhage,
      acute stroke, cerebral edema, and/or normal pressure hydrocephalus on the CT were
      excluded. WMD was quantified on CT using Wahlund's scoring protocol. Osteoporosis
      information was obtained from the chart, which has been diagnosed based on bone
      mineral density (BMD) information. Logistic regression analysis was done to
      determine the association of WMD severity with osteoporosis after controlling for
      confounding vascular risk factors. RESULTS: Of the 505 subjects who were included
      in the study, 188 (37%) had osteoporosis and 171 (91%) of these osteoporotic
      subjects were females. The mean age was 79.8 +/- 7.04 years. The prevalence of
      WMD in osteoporosis subjects was 73%. In the unadjusted logistic regression
      analysis, there was a significant association between WMD severity and
      osteoporosis (odds ratio (OR): 1.10; 95% confidence interval (CI): 1.05 - 1.14; P
      < 0.001) and the significance remained in the adjusted model, after correcting
      for age, sex and all vascular risk factors (OR: 1.11; 95% CI: 1.05 - 1.18; P <
      0.001). CONCLUSION: WMD severity of the brain was associated with osteoporosis in
      the elderly.

PMID- 25780477
TI  - The efficacy of vildagliptin concomitant with insulin therapy in type 2 diabetic
      subjects.
AB  - BACKGROUND: In Japan, dipeptidyl peptidase 4 (DPP4) inhibitors have become
      standard therapeutic agents for type 2 diabetes, and numbers of patients
      receiving insulin therapy combined with DPP4 inhibitors, which is a highly
      effective regimen, are increasing. METHODS: In this study, we evaluated the
      efficacy of vildagliptin administered at the dose of 100 mg twice daily in 57
      patients with type 2 diabetes already receiving insulin treatment. RESULTS: The
      36 patients who simply received add-on vildagliptin showed a 0.6% decrease in
      HbA1c levels, despite a marked insulin dose reduction, mainly bolus insulin, of
      approximately 8.3 units. In addition, body mass index exhibited a significant
      negative correlation with the efficacy of vildagliptin, i.e., DeltaHbA1c. On the
      other hand, the 21 patients switched from 50 mg of sitagliptin to vildagliptin
      showed HbA1c decreases approaching 0.7%. CONCLUSION: Taking into consideration
      that twice-daily oral vildagliptin has already been reported to be advantageous
      in reducing postprandial hyperglycemia, this drug was suggested to be more
      effective in reducing HbA1c than sitagliptin under conditions in which it is used
      as a supplement to basal insulin, as in this study.

PMID- 25780478
TI  - Common features in patients with superior canal dehiscence declining surgical
      treatment.
AB  - BACKGROUND: Superior canal dehiscence (SCD) is a benign condition in which a
      surgical treatment may be considered depending on the patients' tolerance of
      their symptoms. In this study, we aim to identify driving factors behind the
      patients' choice of a surgical management over watchful waiting. METHODS: Sixty
      two patients with cochlear and/or vestibular symptoms and a temporal bone high
      resolution CT (HRCT) scan showing SCD were included in the study. All patients
      have been offered either surgical management or watchful waiting. RESULTS: Of
      these, 28 elected surgery and 34 declined it. The operated group showed more
      cochlear (6.6 vs. 2.4) symptoms than the non-operated group (P < 0.001) except
      for hypoacousis, but no significant difference (P = 0.059) was found for the
      number of vestibular symptoms between both groups (3.4 vs. 1.1). Footstep and
      eating hyperacousis were both present in 57.1% of operated vs. 3% of non-operated
      patients (P < 0.001). Oscillopsia with effort and with walking was found in 50%
      and 35.7% of operated patients, respectively, but none in the non-operated group
      (P < 0.001). Hearing tuning fork at malleolus and Valsalva and pneumatic speculum
      induced vertigo showed a statistically significant difference between the two
      groups (P = 0.003, P < 0.001, P = 0.010 respectively). Cervical vestibular-evoked
      myogenic potential (cVEMP) thresholds, air and bone conduction thresholds, and
      mean air-bone gap (ABG) were similar in the two populations (P > 0.05). The
      average dehiscence size was 4.7 mm (2.0 - 8.0 mm) and 3.8 mm (1.3 - 7.7 mm) in
      the operated and non-operated patients, respectively (P = 0.421). CONCLUSIONS:
      The natures of cochleovestibular signs and symptoms were shown to be key factors
      in patients' choice of a surgical management whereas paraclinical tests seem to
      be less significant in the patients' decision for a surgical treatment.

PMID- 25780479
TI  - Variability in response to hepatitis B vaccine in hemodialysis patients.
AB  - BACKGROUND: Hemodialysis patients are exposed to blood and blood products more
      than the general population and are also at higher risk for hepatitis B (HB)
      contamination. For these reasons, it is highly recommended that this patient
      population gets the HB vaccine. The efficacy of the vaccine is measured by
      measuring titers of antibody in the serum of the patient. A minimum titer of 10
      mIU/mL is considered to be a response. The conversion rate in hemodialysis
      patients ranges from 50% to 80%, as compared to the general population where the
      conversion rate is over 95%. As opposed to the general population, end-stage
      renal patients on hemodialysis do not always respond to the vaccine. The main
      objective in this study was to try to identify factors that may hinder the
      response. Correction of these factors in the future may help non-responders.
      METHODS: This was a retrospective chart review at a single hemodialysis center to
      compare the laboratory and clinical differences between responders and non
      responders. Inclusion criteria are hemodialysis patients who received the HB
      vaccine and patients with concomitant hepatitis C. Exclusion criteria are
      patients who refused the vaccine and patients who did not complete the vaccine
      course. RESULTS: There are a total of 108 subjects included in the study, out of
      which 44 (42.3%) are responders to the HB vaccine. A multivariate logistic
      regression was performed using the statistically significant risk factors as
      identified by the univariate logistic regression, including age range, albumin,
      hemodialysis vintage, vascular access and diabetes status. The results from the
      multivariate logistic regression show that advanced age (P = 0.005) and diabetes
      status (P = 0.003) are found to be strong independent risk factors of responder
      status. The type of vascular access (AVF or other types) is also marginally
      statistically significant (P = 0.05). CONCLUSIONS: In this retrospective chart
      review comparing HB vaccine in responders versus non-responders, we found that
      advanced age and a history of diabetes are independent risk factors in predicting
      responder status.

PMID- 25780480
TI  - Evaluation of Maternal-Fetal Outcomes After Emergency Vaginal Cerclage Performed
      With Shirodkar-McDonald Combined Modified Technique.
AB  - BACKGROUND: Several techniques of emergency vaginal cerclage have been proposed
      in case of unexpected and abrupt cervical incompetence (CI), in order to prolong
      the pregnancy as much as possible and to reduce the adverse maternal-fetal
      outcomes. The aim of our study was to evaluate the effectiveness of emergency
      cervical cerclage, performed with the combined modified Shirodkar-McDonald
      technique. METHODS: We selected 12 cases of emergency vaginal cerclage, performed
      between January 1, 2008 and June 30, 2013. The age of the patients was between 20
      and 38 years (mean 29.0 +/- standard deviation (SD) 5.69), parity between 0 and 2
      (mean 0.7 +/- SD 0.65), and gestational age at the time of admission ranged
      between 17 and 26 weeks (mean 21.0 +/- SD 3.44). In all these cases, we used a
      combined modified Shirodkar-McDonald technique to perform the procedure. RESULTS:
      The neonatal survival rate was 83.3%. The cesarean section rate was 16.7%. The
      average pregnancy prolongation was 89.9 days, higher than that reported for other
      studies in the literature. CONCLUSIONS: We can assume that the emergency vaginal
      cerclage performed with the combined modified Shirodkar-McDonald technique is the
      best option of surgical therapy for the treatment of unexpected and abrupt CI.

PMID- 25780481
TI  - Cross-sectional study of patients with onset of acute coronary syndrome during
      statin therapy.
AB  - BACKGROUND: Although statin therapy significantly reduces cardiovascular
      morbidity and mortality, atherosclerotic plaque progresses in some patients
      taking statins. This study investigated the factors associated with onset of
      acute coronary syndrome (ACS) early after the initiation of statin therapy.
      METHODS: Consecutive patients taking statins who presented with ACS (n = 64) were
      divided into < 1-year and > 1-year groups based on the duration of statin
      therapy. Patient characteristics, coronary risk factors, lesion locations, and
      percutaneous intervention procedures were compared between groups. RESULTS: The <
      1-year group was significantly younger (57.6 +/- 11.9 years vs. 76.6 +/- 9.1
      years, P < 0.01), had significantly higher body mass index (27.22 +/- 4.20
      kg/m(2) vs. 24.60 +/- 4.65 kg/m(2), P < 0.05), higher proportion of males (94%
      vs. 70%, P < 0.05), higher proportion of current smokers (61% vs. 17%, P < 0.01),
      and lower proportions taking aspirin and calcium antagonists (both 17% vs. 57%, P
      < 0.05) than the > 1-year group. In the < 1-year group, there were significant
      correlations between the low-density lipoprotein cholesterol (LDL-C) and
      triglyceride (TG) levels (r = 0.649, P = 0.004) and between the TG and hemoglobin
      (Hb)A1c levels (r = 0.552, P = 0.018), but these correlations were not observed a
      year before admission. TG level was the only parameter associated with LDL-C and
      HbA1c levels. CONCLUSIONS: A linear correlation between the LDL-C and TG levels,
      obesity, older age, male sex, and smoking may be associated with increased risk
      of onset of ACS early after the initiation of statin therapy. Prospective cohort
      studies are needed to further explore these interactions.

PMID- 25780482
TI  - Depression, suicide ideation, and thyroid tumors among ukrainian adolescents
      exposed as children to chernobyl radiation.
AB  - BACKGROUND: The Chernobyl Childhood Illness Program (CCIP) was a humanitarian
      assistance effort funded by the United States Congress. Its purpose was to assist
      the Ukrainian Government to identify and treat adolescents who developed mental
      and physical problems following their exposure as young children to Chernobyl
      radiation. Thirteen years after the Chernobyl nuclear plant accident in 1986, the
      CCIP examined 116,655 Ukrainian adolescents for thyroid diseases. Of these,
      115,191 were also screened for depression, suicide ideation, and psychological
      problems. The adolescents lived in five of Ukraine's seven most Chernobyl
      radiation contaminated provinces. They were up to 6 years of age or in utero when
      exposed to nuclear fallout, or were born up to 45 months after Chernobyl.
      METHODS: Ukrainian endocrinologist and ultrasonographers used physical
      examination and ultrasonography of the neck to evaluate the adolescents for
      thyroid tumors. The adolescents were then screened for depression by the
      Children's Depression Inventory (CDI). After this, Ukrainian psychologists
      conducted individual psychological interviews to corroborate the adolescents' CDI
      responses. RESULTS: Papillary thyroid carcinoma was diagnosed in eight
      adolescents, a high prevalence rate similar to that reported by other studies
      from the Soviet Union. Screening identified thyroid nodules in 1,967 adolescents
      (1.7%). Depression was diagnosed in 15,399 adolescents (13.2%), suicide ideation
      in 813 (5.3%), and attempted suicide in 354 (2.3%). Underlying components of the
      participants' depression were negative mood, interpersonal difficulties, negative
      self-esteem, ineffectiveness, and anhedonia. Depression was greater in females
      (77%). Those with thyroid and psychological problems were referred for treatment.
      CONCLUSIONS: The adolescents screened by CCIP represent the largest Ukrainian
      cohort exposed to Chernobyl radiation as children who were evaluated for both
      thyroid tumors and depression. The group had an increased prevalence of thyroid
      cancer, thyroid tumors, depression, and suicide ideation. CCIP demonstrated that
      psychological problems among Chernobyl exposed adolescents began earlier in life
      than previously reported. They also experienced socioeconomic problems from their
      relocation from radiation-affected areas and from the Soviet's inadequate
      responses to their health needs. CCIP's findings underscore the requirement that
      governments prepare plans to deal promptly with the diagnosis and treatment of
      nuclear accident victims' medical and psychological problems.

PMID- 25780483
TI  - Nurse-led psychological intervention after physical traumas: a randomized
      controlled trial.
AB  - BACKGROUND: Emergency room nurses were trained to provide a short-term
      psychological intervention in physically injured patients with Impact of Event
      Scale (IES) scores > 20. The aims were to study the effects of the psychological
      intervention relative to usual care (UC). METHODS: In a randomized controlled
      trial, psychological distress, daily functioning and the personality traits
      optimism/pessimism were compared with patients who received the UC. The
      interventions were provided 1 - 3 months after discharge. RESULTS: The IES scores
      were significantly reduced in both groups at 3 months (intervention: 41.1 - 28.6,
      P < 0.001 vs. UC: 35.4 - 26.2, P < 0.001), but not significantly different
      between groups. Baseline IES score was a significant predictor of IES scores at 3
      (beta = 0.4, P < 0.05) and 12 months (beta = 0.3, P < 0.05), whereas overall
      daily functioning at 3 months predicted IES scores at 12 months (beta = -0.5, P <
      0.001). Patients receiving intervention became significantly more optimistic
      during the year, and had an increase in overall daily functioning from 3 to 12
      months (P < 0.001). Patients declining intervention were more pessimistic and had
      lower daily functioning. Patients who talked with nurses with more training in
      psychological processing had a larger reduction in IES symptoms at 3 months (beta
      = -0.3, P = 0.081). CONCLUSION: The nurse-led intervention had a significant
      effect on optimism and overall daily functioning. Nurses may become a low-cost
      option to perform short-term psychological interventions with physically injured
      hospitalized patients.

PMID- 25780484
TI  - Effectiveness of physical exercise to reduce cardiovascular risk factors in
      youths: a randomized clinical trial.
AB  - BACKGROUND: The aim of the current study was to test the effectiveness of a
      physical activity and exercise-based program in a clinical context to reduce
      cardiovascular risk factors in children and adolescents. METHODS: A randomized
      clinical trial was conducted in a pediatric preventive outpatient clinic.
      Intervention was 14 weeks of exercise for the intervention group or general
      health advice for the control group. The primary and the secondary outcomes were
      reduction of cardiovascular risk factors and the feasibility and the
      effectiveness of clinical advice plan to practice physical exercises at home.
      RESULTS: A total of 134 children were screened; 26 met eligibility criteria. Of
      these, 10 were allocated in the exercise intervention group and nine were
      included in the control group until the end of the intervention. Those patients
      who discontinued the intervention had the lowest scores of z-BMI (P = 0.033) and
      subscapular skin fold (P = 0.048). After 14 weeks of intervention, no statistical
      differences were found between the groups. High-density lipoprotein cholesterol
      (HDL-C) was higher in the exercise group, with a mild tendency to be significant
      (P = 0.066). Patients who adhere to treatment had diastolic blood pressure
      decreased from baseline to the end of the follow-up period in the control group
      (P = 0.013). Regardless of this result, the other comparisons within the group
      were not statistically different between T0 and T14. CONCLUSION: A low-cost
      physical activity advice intervention presented many barriers for implementation
      in routine clinical care, limiting its feasibility and evaluation of
      effectiveness to reduce cardiovascular risk factors.

PMID- 25780485
TI  - Aortic dissection presenting as acute subtotal left main coronary artery
      occlusion: a case approach and review of the literature.
AB  - Aortic dissection is the most common fatal condition of the aorta, yet it is
      often missed on initial clinical presentation. Aortic dissection associated with
      acute coronary syndrome (ACS) is relatively rare, but if it occurs, it can be
      diagnostically challenging, and the condition can be fatal. Here we describe a
      case of aortic dissection presenting as ST-segment elevation myocardial
      infarction (STEMI) managed via the transradial approach. We describe the current
      literature on the subject. 

PMID- 25780486
TI  - A case report on a rare disease: dyskeratosis congenita.
AB  - Dyskeratosis congenita (DC) is a rare hereditary disorder characterized by bone
      marrow failure, cancer predisposition (11-fold increase compared to general
      population), ectodermal dysplasia (nail dystrophy, oral leukoplakia, and abnormal
      skin pigmentation) and other additional somatic abnormalities. A 22-year-old man
      presented with fever, chills, and a painful throat. Leukoplakia was noted on his
      tongue and some of his fingers and toe nails were markedly dystrophic. His skin
      seemed spotted with pigmentation on the anterior chest and neck. Patient reported
      family history of "blood disease" and leukemia. He was admitted for the
      management of neutropenic fever (102.9  degrees F, WBC: 940, ANC: 404, platelets:
      21,000 and Hb: 9.2), and was put on broad spectrum antibiotics. A bone marrow
      biopsy revealed normocellular marrow with erythroid predominance and mild
      dyserythropoiesis. Chromosomal analysis indicated no numerical or structural
      chromosomal abnormalities. The fluorescence in situ hybridization report did not
      reveal any assay specific abnormalities. Viral marker for hepatitis and studies
      of autoimmune antibodies showed negative results. CT scan had shown splenomegaly.
      Patient was discharged after he has been fever and symptoms free, with a follow
      up at hematology clinic. Individuals with DC most commonly present with skin
      pigmentation, dystrophic nails and leukoplakia, as presented in this case.
      Genetic abnormality was not confirmed in our patient, but it is suggested that X
      linked recessive pattern would be significant because of greater prevalence in
      men than in women (10:1). The distribution of blood counts and bone marrow biopsy
      categorizes our patient in the moderate aplastic anemia class which is the most
      prevalent pattern. When fever in young patients with a failing bone marrow is
      diagnosed, it is important that physicians rule out the possible underlying
      causes. DC is a rare disease, but can be diagnosed by simple inspection of the
      mucocutaneous abnormalities. DC is a severe multisystem disorder associated with
      premature morbidity and mortality. We believe that reporting this case would add
      more information to the existing fund of knowledge. 

PMID- 25780487
TI  - Paranoid personality masking an atypical case of frontotemporal dementia.
AB  - Frontotemporal dementia (FTD) is a debilitating disease that is well described in
      the "Diagnostic and statistical manual of mental disorders, fifth edition (DSM
      5)", and typically presents with memory impairment, progressive decline in
      cortical functioning, and behavioral changes. Age of onset is generally in the
      late fifties, and usually the first presentation involves a change in behavior
      and emotional blunting. Treatment of FTD involves management of any
      neurobehavioral symptoms while trials of atypical antipsychotics are ongoing but
      suggest some efficacy. We present a case of a patient who first presented with
      severe paranoid personality traits and frank persecutory delusions. This atypical
      presentation of our patient first led to her incorrect diagnosis of a psychotic
      disorder and paranoid personality disorder. As a result of this diagnosis, she
      was treated unsuccessfully. A subsequent magnetic resonance imaging (MRI) then
      showed atrophy of frontal and temporal lobes bilaterally (left more prominent
      than right) which confirmed the diagnosis of FTD. The importance of this case
      involves the atypical presentation of paranoia and delusions, and our patient's
      incorrect diagnosis based on her clinical presentation led to a trial of
      unsuccessful treatment. Only after performing an MRI, which showed atrophy, was
      the patient appropriately treated and deemed medically stable. This case report
      illustrates the importance of considering a rare presentation of frontotemporal
      lobe dementia with patients who are in the typical age range and present with
      paranoia and delusions. 

PMID- 25780488
TI  - Economic problems and mental disorders in Japanese pregnant women.

PMID- 25780489
TI  - Correction: Aung Zaw Win, Renal Cell Carcinoma Metastasis to the Gallbladder
      Detected by FDG-PET/CT.
AB  - [This corrects the article DOI: 10.14740/jocmr1886w.]. 

PMID- 25780490
TI  - Host, vehicular and environmental factors responsible for road traffic crashes in
      a Nigerian city: identifiable issues for road traffic injury control.
AB  - INTRODUCTION: Road traffic injury (RTI) has assumed major public health
      importance world-wide and the burden is heavier on the health-care infrastructure
      of countries in Sub-Saharan Africa. In Nigeria, RTI is the leading cause of
      trauma related morbidity and mortality. While there are some published
      epidemiological reports on RTI in the region, studies on the mechanism of
      causation of road traffic crashes (RTC) are not available. METHODS: Over a 9
      month period, we prospectively captured the 571 victims of RTC presenting to a
      single tertiary health care center in Nigeria. Data collected include demographic
      data, Mechanism of causation of RTC, Injuries sustained and outcomes. RESULTS:
      Over three-quarters of the victims are young people and half were either traders
      (27.5%) or students (20%). Pedestrians, motorcycle riders and open truck
      occupants (people sitting at the rear loading compartment of trucks) often had
      fatal injuries. Analysis of collision patterns showed that lone crashes were the
      most frequent though car-to-motorcycle crashes caused a quarter of the deaths.
      Host factors (over-speeding driver, driver misjudgment, sleeping driver etc.)
      were responsible for four-fifths of the crashes while vehicular and environmental
      factors accounted for the remaining. On binary regression analysis, head injured
      victims had higher odds of dying than the non-head injured (Odds ratio = 6.5).
      CONCLUSION: This paper elucidates the mechanisms of causation of and types of
      injuries sustained following RTC in Nigeria and thus provide opportunities for
      prevention and control of this unacceptable situation.

PMID- 25780491
TI  - Aluminium in Allergies and Allergen immunotherapy.
AB  - Aluminium is a hot topic in the current debate. Exposure occurs due to
      environmental, dietary and intentional exposure to aluminium, such as in vaccines
      where it was introduced in 1926. In spite of the fact that it is a typical Th2
      adjuvant, aluminium redirects the immune response in systemic allergen
      immunotherapy (SIT) upon prolonged immunization. SIT in the US, and SLIT in
      general, are at present non-adjuvanted therapies, but in Europe aluminium is used
      as adjuvant in most SIT preparations. It enhances the safety of SIT by local
      deposition of the allergen. Undesired properties of aluminium adjuvants comprise
      acute and chronic inflammation at the injection site, its Th2 immune stimulatory
      capacity, its accumulation besides biodistribution in the body. The adjuvant and
      safety profile of aluminium adjuvants in allergy vaccines are discussed, as well
      as the need for putting modern delivery systems and adjuvants on the fast track. 

PMID- 25780492
TI  - The IgE response to Ascaris molecular components is associated with clinical
      indicators of asthma severity.
AB  - BACKGROUND: Asthma is a common chronic disease worldwide and Ascaris lumbricoides
      infection (ascariasis) is frequent in tropical regions. However, the effect of
      ascariasis on asthma severity has not been sufficiently explored. We sought to
      evaluate the influence of the IgE immune response to Ascaris extract and purified
      house dust mites (HDM) and Ascaris allergens on indicators of asthma severity in
      patients living in the tropics. METHODS: Asthmatic patients from Cartagena,
      Colombia were recruited. Clinical assessment included questionnaires, physical
      examination, allergy skin tests, spirometry, parasite stool examination and IgE
      antibody measurements. Asthma was diagnosed by a physician according to validated
      criteria. Indicators of severity were occurrence of severe dyspnea episodes,
      night awakenings events, > 4 emergency room (ER) visits and hospitalizations
      during the last year. Specific IgE to Der p 2, Ascaris spp., Blomia tropicalis
      and Dermatophagoides pteronyssinus extracts was determined by ImmunoCap. IgE to
      tropomyosins (Asc l 3, Blo t 10 and Der p 10), Blo t 5 and Asc s 1 was detected
      by ELISA. Logistic regression analyses were used to explore the relationships
      between sensitization and indicators of asthma severity. RESULTS: After
      adjustment for HDM sensitization, Ascaris sensitization remained associated with
      severe dyspnea (aOR: 1.90, 95% CI: 1.08 - 3.34, p = 0.03) and > 4 ER visits (aOR:
      2.23, 95% CI: 1.15 - 4.30, p = 0.02). We also found that sensitization to the
      species specific markers Blo t 5 and Asc s 1, as well as the cross-reactive
      tropomyosins of D. pteronyssinus and Ascaris were associated with > 4 ER visits.
      Der p 2 sensitization was associated with bronchodilator responsiveness (aOR:
      2.24: 1.25-4.02, p = 0.01). Remarkably, significantly higher IgE levels to HDM
      species specific allergens were found in Ascaris sensitized patients.
      CONCLUSIONS: In this tropical population, IgE sensitization to Ascaris and the
      cross-reactive tropomyosins was frequent and associated with clinical indicators
      of asthma severity. The significant relationship between sensitization to the
      nematode-specific marker Asc s 1 and ER attendance supports these findings.
      Moreover, ascariasis increases the human IgE responses to HDM specific allergens.

PMID- 25780493
TI  - Intralymphatic immunotherapy.
AB  - Gold Standard allergen-specific immunotherapy is associated with low efficacy
      because it requires either many subcutaneous injections of allergen or even more
      numerous sublingual allergen administrations to achieve amelioration of symptoms.
      Intralymphatic vaccination can maximize immunogenicity and hence efficacy. We and
      others have demonstrated that as few as three low dose intralymphatic allergen
      administrations are sufficient to effectively alleviate symptoms. Results of
      recent prospective and controlled trials suggest that this strategy may be an
      effective form of allergen immunotherapy. 

PMID- 25780494
TI  - Standards in Genomic Sciences: New beginnings to reflect the association between
      the journal and BMC.

PMID- 25780496
TI  - Genome sequence of the Lotus corniculatus microsymbiont Mesorhizobium loti strain
      R88B.
AB  - Mesorhizobium loti strain R88B was isolated in 1993 in the Rocklands range in
      Otago, New Zealand from a Lotus corniculatus root nodule. R88B is an aerobic,
      Gram-negative, non-spore-forming rod. This report reveals the genome of M. loti
      strain R88B contains a single scaffold of size 7,195,110 bp which encodes 6,950
      protein-coding genes and 66 RNA-only encoding genes. This genome does not harbor
      any plasmids but contains the integrative and conjugative element ICEMlSym(R7A),
      also known as the R7A symbiosis island, acquired by horizontal gene transfer in
      the field environment from M. loti strain R7A. It also contains a mobilizable
      genetic element ICEMladh(R88B), that encodes a likely adhesin gene which has
      integrated downstream of ICEMlSym(R7A), and three acquired loci that together
      allow the utilization of the siderophore ferrichrome. This rhizobial genome is
      one of 100 sequenced as part of the DOE Joint Genome Institute 2010 Genomic
      Encyclopedia for Bacteria and Archaea-Root Nodule Bacteria (GEBA-RNB) project. 

PMID- 25780495
TI  - Complete genome sequence of DSM 30083(T), the type strain (U5/41(T)) of
      Escherichia coli, and a proposal for delineating subspecies in microbial
      taxonomy.
AB  - Although Escherichia coli is the most widely studied bacterial model organism and
      often considered to be the model bacterium per se, its type strain was until now
      forgotten from microbial genomics. As a part of the G enomic E ncyclopedia of B
      acteria and A rchaea project, we here describe the features of E. coli DSM
      30083(T) together with its genome sequence and annotation as well as novel
      aspects of its phenotype. The 5,038,133 bp containing genome sequence includes
      4,762 protein-coding genes and 175 RNA genes as well as a single plasmid.
      Affiliation of a set of 250 genome-sequenced E. coli strains, Shigella and
      outgroup strains to the type strain of E. coli was investigated using digital
      DNA:DNA-hybridization (dDDH) similarities and differences in genomic G+C content.
      As in the majority of previous studies, results show Shigella spp. embedded
      within E. coli and in most cases forming a single subgroup of it. Phylogenomic
      trees also recover the proposed E. coli phylotypes as monophyla with minor
      exceptions and place DSM 30083(T) in phylotype B2 with E. coli S88 as its closest
      neighbor. The widely used lab strain K-12 is not only genomically but also
      physiologically strongly different from the type strain. The phylotypes do not
      express a uniform level of character divergence as measured using dDDH, however,
      thus an alternative arrangement is proposed and discussed in the context of
      bacterial subspecies. Analyses of the genome sequences of a large number of E.
      coli strains and of strains from > 100 other bacterial genera indicate a value of
      79-80% dDDH as the most promising threshold for delineating subspecies, which in
      turn suggests the presence of five subspecies within E. coli. 

PMID- 25780497
TI  - Genome sequence of Ensifer medicae Di28; an effective N2-fixing microsymbiont of
      Medicago murex and M. polymorpha.
AB  - Ensifer medicae Di28 is an aerobic, motile, Gram-negative, non-spore-forming rod
      that can exist as a soil saprophyte or as a legume microsymbiont of Medicago spp.
      Di28 was isolated in 1998 from a nodule recovered from the roots of M. polymorpha
      growing in the south east of Sardinia (Italy). Di28 is an effective microsymbiont
      of the annual forage legumes M. polymorpha and M. murex and is capable of
      establishing a partially effective symbiotic association with the perennial M.
      sativa. Here we describe the features of E. medicae Di28, together with genome
      sequence information and its annotation. The 6,553,624 bp standard draft genome
      is arranged into 104 scaffolds of 104 contigs containing 6,394 protein-coding
      genes and 75 RNA-only encoding genes. This rhizobial genome is one of 100
      sequenced as part of the DOE Joint Genome Institute 2010 Genomic Encyclopedia for
      Bacteria and Archaea-Root Nodule Bacteria (GEBA-RNB) project. 

PMID- 25780498
TI  - Genome sequence of the dark pink pigmented Listia bainesii microsymbiont
      Methylobacterium sp. WSM2598.
AB  - Strains of a pink-pigmented Methylobacterium sp. are effective nitrogen- (N2)
      fixing microsymbionts of species of the African crotalarioid genus Listia. Strain
      WSM2598 is an aerobic, motile, Gram-negative, non-spore-forming rod isolated in
      2002 from a Listia bainesii root nodule collected at Estcourt Research Station in
      South Africa. Here we describe the features of Methylobacterium sp. WSM2598,
      together with information and annotation of a high-quality draft genome sequence.
      The 7,669,765 bp draft genome is arranged in 5 scaffolds of 83 contigs, contains
      7,236 protein-coding genes and 18 RNA-only encoding genes. This rhizobial genome
      is one of 100 sequenced as part of the DOE Joint Genome Institute 2010 G enomic E
      ncyclopedia for B acteria and A rchaea- R oot N odule B acteria (GEBA-RNB)
      project. 

PMID- 25780499
TI  - Genome sequence of the Lotus spp. microsymbiont Mesorhizobium loti strain R7A.
AB  - Mesorhizobium loti strain R7A was isolated in 1993 in Lammermoor, Otago, New
      Zealand from a Lotus corniculatus root nodule and is a reisolate of the inoculant
      strain ICMP3153 (NZP2238) used at the site. R7A is an aerobic, Gram-negative, non
      spore-forming rod. The symbiotic genes in the strain are carried on a 502-kb
      integrative and conjugative element known as the symbiosis island or
      ICEMlSym(R7A). M. loti is the microsymbiont of the model legume Lotus japonicus
      and strain R7A has been used extensively in studies of the plant-microbe
      interaction. This report reveals that the genome of M. loti strain R7A does not
      harbor any plasmids and contains a single scaffold of size 6,529,530 bp which
      encodes 6,323 protein-coding genes and 75 RNA-only encoding genes. This rhizobial
      genome is one of 100 sequenced as part of the DOE Joint Genome Institute 2010
      Genomic Encyclopedia for Bacteria and Archaea-Root Nodule Bacteria (GEBA-RNB)
      project. 

PMID- 25780500
TI  - Genome sequence of the Lotus spp. microsymbiont Mesorhizobium loti strain
      NZP2037.
AB  - Mesorhizobium loti strain NZP2037 was isolated in 1961 in Palmerston North, New
      Zealand from a Lotus divaricatus root nodule. Compared to most other M. loti
      strains, it has a broad host range and is one of very few M. loti strains able to
      form effective nodules on the agriculturally important legume Lotus pedunculatus.
      NZP2037 is an aerobic, Gram negative, non-spore-forming rod. This report reveals
      that the genome of M. loti strain NZP2037 does not harbor any plasmids and
      contains a single scaffold of size 7,462,792 bp which encodes 7,318 protein
      coding genes and 70 RNA-only encoding genes. This rhizobial genome is one of 100
      sequenced as part of the DOE Joint Genome Institute 2010 Genomic Encyclopedia for
      Bacteria and Archaea-Root Nodule Bacteria (GEBA-RNB) project. 

PMID- 25780501
TI  - Non-contiguous finished genome sequence and description of Clostridium saudii sp.
      nov.
AB  - Clostridium saudii strain JCC(T) sp. nov. is the type strain of C. saudii sp.
      nov., a new species within the genus Clostridia. This strain, whose genome is
      described here, was isolated from a fecal sample collected from an obese 24-year
      old (body mass index 52 kg/m2) man living in Jeddah, Saudi Arabia. C. saudii is a
      Gram-positive, anaerobic bacillus. Here we describe the features of this
      organism, together with the complete genome sequence and annotation. The
      3,653,762 bp long genome contains 3,452 protein-coding and 53 RNA genes,
      including 4 rRNA genes. 

PMID- 25780502
TI  - High quality draft genome sequence and description of Occidentia massiliensis
      gen. nov., sp. nov., a new member of the family Rickettsiaceae.
AB  - The family Rickettsiaceae currently includes two genera: Orientia that contains
      one species, Orientia tsutsugamushi, and Rickettsia that contains 28 species.
      Occidentia massiliensis gen. nov., sp. nov. strain OS118(T) is the type strain of
      O. massiliensis gen. nov., sp. nov., the type species of the new genus Occidentia
      gen. nov. within the family Rickettsiaceae. This strain, whose genome is
      described here, was isolated in France from the soft tick Ornithodoros sonrai
      collected in Senegal. O. massiliensis is an aerobic, rod-shaped, Gram-negative,
      obligate intracellular bacillus that may be cultivated in BME/CTVM2 cells. Here
      we describe the features of O. massiliensis, together with the complete genomic
      sequencing and annotation. The 1,469,252 bp long genome (1 chromosome but no
      plasmid) contains 1,670 protein-coding and 41 RNA genes, including one rRNA
      operon. 

PMID- 25780504
TI  - An Updated genome annotation for the model marine bacterium Ruegeria pomeroyi DSS
      3.
AB  - When the genome of Ruegeria pomeroyi DSS-3 was published in 2004, it represented
      the first sequence from a heterotrophic marine bacterium. Over the last ten
      years, the strain has become a valuable model for understanding the cycling of
      sulfur and carbon in the ocean. To ensure that this genome remains useful, we
      have updated 69 genes to incorporate functional annotations based on new
      experimental data, and improved the identification of 120 protein-coding regions
      based on proteomic and transcriptomic data. We review the progress made in
      understanding the biology of R. pomeroyi DSS-3 and list the changes made to the
      genome. 

PMID- 25780503
TI  - Complete genome sequence of Planctomyces brasiliensis type strain (DSM 5305(T)),
      phylogenomic analysis and reclassification of Planctomycetes including the
      descriptions of Gimesia gen. nov., Planctopirus gen. nov. and Rubinisphaera gen.
      nov. and emended descriptions of the order Planctomycetales and the family
      Planctomycetaceae.
AB  - Planctomyces brasiliensis Schlesner 1990 belongs to the order Planctomycetales,
      which differs from other bacterial taxa by several distinctive features such as
      internal cell compartmentalization, multiplication by forming buds directly from
      the spherical, ovoid or pear-shaped mother cell and a cell wall consisting of a
      proteinaceous layer rather than a peptidoglycan layer. The first strains of P.
      brasiliensis, including the type strain IFAM 1448(T), were isolated from a water
      sample of Lagoa Vermelha, a salt pit near Rio de Janeiro, Brasil. This is the
      second completed genome sequence of a type strain of the genus Planctomyces to be
      published and the sixth type strain genome sequence from the family
      Planctomycetaceae. The 6,006,602 bp long genome with its 4,811 protein-coding and
      54 RNA genes is a part of the G enomic E ncyclopedia of Bacteria and Archaea
      project. Phylogenomic analyses indicate that the classification within the
      Planctomycetaceae is partially in conflict with its evolutionary history, as the
      positioning of Schlesneria renders the genus Planctomyces paraphyletic. A re
      analysis of published fatty-acid measurements also does not support the current
      arrangement of the two genera. A quantitative comparison of phylogenetic and
      phenotypic aspects indicates that the three Planctomyces species with type
      strains available in public culture collections should be placed in separate
      genera. Thus the genera Gimesia, Planctopirus and Rubinisphaera are proposed to
      accommodate P. maris, P. limnophilus and P. brasiliensis, respectively.
      Pronounced differences between the reported G + C content of Gemmata
      obscuriglobus, Singulisphaera acidiphila and Zavarzinella formosa and G + C
      content calculated from their genome sequences call for emendation of their
      species descriptions. In addition to other features, the range of G + C values
      reported for the genera within the Planctomycetaceae indicates that the
      descriptions of the family and the order should be emended. 

PMID- 25780505
TI  - Non-contiguous finished genome sequence of Ornithobacterium rhinotracheale strain
      H06-030791.
AB  - The Gram-negative, pleomorphic, rod-shaped bacterium Ornithobacterium
      rhinotracheale is a cause of pneumonia and airsacculitis in poultry. It is a
      member of the family Flavobacteriaceae of the phylum "Bacteroidetes". O.
      rhinotracheale strain H06-030791 was isolated from the lung of a turkey in North
      Carolina in 2006. Its genome consists of a circular chromosome of 2,319,034 bp in
      length with a total of 2243 protein-coding genes and nine RNA genes. Genome
      sequences are available for two additional strains of O. rhinotracheale, isolated
      in 1988 and 1995, the latter described in a companion genome report in this issue
      of SIGS. The genome sequence of O. rhinotracheale strain H06-030791, a more
      contemporary isolate, will be of value in establishing core and pan-genomes for
      O. rhinotracheale and elucidating its evolutionary history. 

PMID- 25780506
TI  - The complete genome sequence of the rumen methanogen Methanobacterium formicicum
      BRM9.
AB  - Methanobacterium formicicum BRM9 was isolated from the rumen of a New Zealand
      Friesan cow grazing a ryegrass/clover pasture, and its genome has been sequenced
      to provide information on the phylogenetic diversity of rumen methanogens with a
      view to developing technologies for methane mitigation. The 2.45 Mb BRM9
      chromosome has an average G + C content of 41%, and encodes 2,352 protein-coding
      genes. The genes involved in methanogenesis are comparable to those found in
      other members of the Methanobacteriaceae with the exception that there is no [Fe]
      hydrogenase dehydrogenase (Hmd) which links the methenyl-H4MPT reduction directly
      with the oxidation of H2. Compared to the rumen Methanobrevibacter strains, BRM9
      has a much larger complement of genes involved in determining oxidative stress
      response, signal transduction and nitrogen fixation. BRM9 also has genes for the
      biosynthesis of the compatible solute ectoine that has not been reported to be
      produced by methanogens. The BRM9 genome has a prophage and two CRISPR repeat
      regions. Comparison to the genomes of other Methanobacterium strains shows a core
      genome of ~1,350 coding sequences and 190 strain-specific genes in BRM9, most of
      which are hypothetical proteins or prophage related. 

PMID- 25780507
TI  - Complete genome sequence of Ornithobacterium rhinotracheale strain ORT-UMN 88.
AB  - Ornithobacterium rhinotracheale strain ORT-UMN 88 is a Gram-negative,
      pleomorphic, rod-shaped bacterium and an etiologic agent of pneumonia and
      airsacculitis in poultry. It is a member of the family Flavobacteriaceae of the
      phylum Bacteroidetes. O. rhinotracheale strain ORT-UMN 88 was isolated from the
      pneumonic lung of a turkey in 1995. It was the isolate first used to
      experimentally reproduce disease in turkeys and has since been the focus of
      investigations characterizing potential virulence factors of the bacterium. The
      genome of O. rhinotracheale strain ORT-UMN 88 consists of a circular chromosome
      of 2,397,867 bp with a total of 2300 protein-coding genes, nine RNA genes, and
      one noncoding RNA gene. A companion paper in this issue of SIGS reports the non
      contiguous finished genome sequence of an additional strain of O. rhinotracheale,
      isolated in 2006. 

PMID- 25780508
TI  - Metazen - metadata capture for metagenomes.
AB  - BACKGROUND: As the impact and prevalence of large-scale metagenomic surveys grow,
      so does the acute need for more complete and standards compliant metadata.
      Metadata (data describing data) provides an essential complement to experimental
      data, helping to answer questions about its source, mode of collection, and
      reliability. Metadata collection and interpretation have become vital to the
      genomics and metagenomics communities, but considerable challenges remain,
      including exchange, curation, and distribution. Currently, tools are available
      for capturing basic field metadata during sampling, and for storing, updating and
      viewing it. Unfortunately, these tools are not specifically designed for
      metagenomic surveys; in particular, they lack the appropriate metadata collection
      templates, a centralized storage repository, and a unique ID linking system that
      can be used to easily port complete and compatible metagenomic metadata into
      widely used assembly and sequence analysis tools. RESULTS: Metazen was developed
      as a comprehensive framework designed to enable metadata capture for metagenomic
      sequencing projects. Specifically, Metazen provides a rapid, easy-to-use portal
      to encourage early deposition of project and sample metadata. CONCLUSIONS:
      Metazen is an interactive tool that aids users in recording their metadata in a
      complete and valid format. A defined set of mandatory fields captures vital
      information, while the option to add fields provides flexibility.

PMID- 25780509
TI  - Quality scores for 32,000 genomes.
AB  - BACKGROUND: More than 80% of the microbial genomes in GenBank are of 'draft'
      quality (12,553 draft vs. 2,679 finished, as of October, 2013). We have examined
      all the microbial DNA sequences available for complete, draft, and Sequence Read
      Archive genomes in GenBank as well as three other major public databases, and
      assigned quality scores for more than 30,000 prokaryotic genome sequences.
      RESULTS: Scores were assigned using four categories: the completeness of the
      assembly, the presence of full-length rRNA genes, tRNA composition and the
      presence of a set of 102 conserved genes in prokaryotes. Most (~88%) of the
      genomes had quality scores of 0.8 or better and can be safely used for standard
      comparative genomics analysis. We compared genomes across factors that may
      influence the score. We found that although sequencing depth coverage of over
      100x did not ensure a better score, sequencing read length was a better indicator
      of sequencing quality. With few exceptions, most of the 30,000 genomes have
      nearly all the 102 essential genes. CONCLUSIONS: The score can be used to set
      thresholds for screening data when analyzing "all published genomes" and
      reference data is either not available or not applicable. The scores highlighted
      organisms for which commonly used tools do not perform well. This information can
      be used to improve tools and to serve a broad group of users as more diverse
      organisms are sequenced. Unexpectedly, the comparison of predicted tRNAs across
      15,000 high quality genomes showed that anticodons beginning with an 'A' (codons
      ending with a 'U') are almost non-existent, with the exception of one arginine
      codon (CGU); this has been noted previously in the literature for a few genomes,
      but not with the depth found here.

PMID- 25780510
TI  - Gastric metastasis from primary lung adenocarcinoma mimicking primary gastric
      cancer.
AB  - Gastric metastases from lung adenocarcinoma are rare. Because gastric metastasis
      grossly resembles advanced gastric cancer, it is difficult to diagnose gastric
      metastasis especially when the histology of the primary lung cancer is
      adenocarcinoma. We describe a case of gastric metastasis from primary lung
      adenocarcinoma mimicking Borrmann type IV primary gastric cancer. A 68-year-old
      man with known lung adenocarcinoma with multiple bone metastases had been
      experiencing progressive epigastric pain and dyspepsia over one year.
      Esophagogastroduodenoscopy revealed linitis plastica-like lesions in the fundus
      of the stomach. Pathologic examination revealed a moderately differentiated
      adenocarcinoma with submucosal infiltration. Positive immunohistochemical
      staining for thyroid transcription factor-1 (TTF-1) and napsin A (Nap-A)
      confirmed that the metastasis was pulmonary in origin. The patient had been
      treated with palliative chemotherapy for the lung cancer and had lived for over
      fifteen months after the diagnosis of gastric metastasis. Clinicians should be
      aware of the possibility of gastric metastasis in patients with primary lung
      adenocarcinoma, and additional immunohistochemical staining for Nap-A as well as
      TTF-1 may help in differentiating its origin. 

PMID- 25780511
TI  - Dehydroepiandrosterone sulfate as a risk factor for premature myocardial
      infarction: a comparative study.
AB  - BACKGROUND: This study aimed to evaluate some of the major risk factors of
      myocardial infarction including dehydroepiandrosterone sulfate in patients with
      premature myocardial infarction (age <50 years old) and myocardial infarction
      (age >=50 years). METHODS: This is a parallel case-control study on 50 premature
      myocardial infarction patients and 50 myocardial infarction patients. We also
      recruited 50 matched participants for each of the two groups. Patients and their
      control groups were assessed for dehydroepiandrosterone sulfate serum level,
      diabetes mellitus, hyperlipidemia, hypertriglyceridemia, and hypertension. In
      addition, family history of cardiovascular disease and current smoking was
      recorded. Univariate and multivariate logistic regression analyses were performed
      to evaluate predictors of premature myocardial infarction and myocardial
      infarction. RESULTS: No significant differences were observed between the
      demographic data of patients and their controls. The dehydroepiandrosterone
      sulfate serum level was significantly higher in patients with premature
      myocardial infarction compared with controls. Multivariate logistic regression
      analysis revealed only serum dehydroepiandrosterone sulfate
      dehydroepiandrosterone sulfate level to be significantly associated with
      premature myocardial infarction (odds ratio, 2.65; 95% confidence interval, 1.44
      to 4.877; P = 0.002). Additionally, hypertension was found to be associated with
      myocardial infarction. CONCLUSION: Higher levels of serum dehydroepiandrosterone
      sulfate level are associated with premature myocardial infarction but not with
      myocardial infarction, and this association is independent of the effects of
      other risk factors.

PMID- 25780512
TI  - Relationship between Neck Length, Sleep, and Cardiovascular Risk Factors.
AB  - BACKGROUND: Neck circumference, as a predicator of obesity, is a well-known risk
      factor for obstructive sleep apnea and cardiovascular diseases. However, little
      research exists on neck length associated with these factors. This study explored
      the association of neck length with sleep and cardiovascular risk factors by
      measuring midline neck length (MNL) and lateral neck length (LNL). METHODS: We
      examined 240 patients aged 30 to 75 years who visited a health check-up center
      between January 2012 and July 2012. Patients with depressive disorder or sleep
      disturbance were excluded from this study. MNL from the upper margin of the hyoid
      bone to the jugular notch and LNL from the mandibular angle to the mid-portion of
      the ipsilateral clavicle were measured twice and were adjusted by height to
      determine their relationship with sleep and cardiovascular disease risk factors.
      RESULTS: Habitual snorers had shorter LNL height ratios (P = 0.011), MNL height
      ratios in men (P = 0.062), and MNL height ratios in women (P = 0.052). Those
      snoring bad enough to annoy others had shorter MNL height ratios in men (P =
      0.083) and women (P = 0.035). Men with objective sleep apnea had longer distances
      from the mandible to the hyoid bone to the mandible (P = 0.057). Men with
      metabolic syndrome had significantly shorter LNL height ratios (P = 0.021), and
      women with diabetes, hyperlipidemia, and metabolic syndrome had shorter MNL
      height ratios (P < 0.05). CONCLUSION: This study shows that a short neck by
      measuring the MNL is probably associated with snoring. In addition, MNL is
      related to cardiovascular disease risk factors in women.

PMID- 25780513
TI  - Association between Muscle Loss and Urinary Incontinence in Elderly Korean Women.
AB  - BACKGROUND: Incontinence and muscle loss are important senior health issues.
      Nevertheless, there are no available domestic or international studies on the
      association between urinary incontinence and muscle loss. The aim of this study
      was to investigate the association between muscle loss and urinary incontinence
      in elderly Korean woman. METHODS: Korean women (1,313) >=65 years of age whose
      complete body composition data were collected using dual X-ray absorptiometry
      were analyzed from the Fourth Korean National Health and Nutritional Examination
      Surveys. Class I and II losses of the appendicular, truncal, and total muscle
      mass were defined using adjustments for weight and height. Each participant's
      incontinence status was collected using constructed questionnaires. Multiple
      logistic regression was performed to examine the association between muscle loss
      and incontinence. RESULTS: On the basis of physician-diagnosed incontinence,
      weight- and height-adjusted muscle loss showed no association with urinary
      incontinence (weight-adjusted muscle loss: class I adjusted odds ratio [aOR],
      0.77; 95% confidence interval [CI], 0.34 to 1.73; class II aOR, 1.37; 95% CI,
      0.59 to 3.18; height-adjusted muscle loss: class I aOR, 0.51; 95% CI, 0.18 to
      1.51; class II aOR, 1.86; 95% CI, 0.22 to 15.79). Similar results were observed
      for truncal muscle and total muscle mass as well as self-reported urinary
      incontinence. CONCLUSION: Our study found no association between urinary
      incontinence and appendicular, truncal, and total muscle loss in elderly Korean
      women.

PMID- 25780514
TI  - Anaplastic lymphoma kinase-positive anaplastic large cell lymphoma arising in a
      patient with hypersensitivity to mosquito bites.
AB  - Hypersensitivity to mosquito bites is defined as the appearance of intense skin
      reactive lesions and systemic symptoms subsequent to mosquito bites. Most cases
      of hypersensitivity to mosquito bites reported thus far have been associated with
      chronic Epstein-Barr virus infection or natural killer cell leukemia/lymphoma. In
      this study, we describe the case of an 18-year-old Korean boy who had
      hypersensitivity to mosquito bites associated with primary systemic anaplastic
      lymphoma kinase-positive anaplastic large cell lymphoma. After a mosquito bite,
      the patient developed a progressive cutaneous nodule on his left lower leg and
      regional lymphadenopathy in the left inguinal area. The histopathological and
      immunohistochemical findings suggested anaplastic lymphoma kinase-positive
      anaplastic large cell lymphoma. Positron emission tomography-computed tomography
      revealed increased fluorodeoxyglucose uptake in the left T4 vertebrae, left
      external iliac lymph nodes, left inguinal lymph nodes, and lateral subcutaneous
      region of the left lower leg. According to the clinical, histopathological, and
      immunohistochemical findings, as well as the imaging data, the patient was
      diagnosed with primary systemic anaplastic lymphoma kinase-positive anaplastic
      large cell lymphoma. Consequently, the patient received a total of 6 cycles of
      cyclophosphamide + doxorubicin + vincristine + prednisolone chemotherapy at 3
      week intervals, after which the lesions regressed. 

PMID- 25780515
TI  - Comments on statistical issues in january 2015.

PMID- 25780516
TI  - Association between Environmental Dioxin-Related Toxicants Exposure and Adverse
      Pregnancy Outcome: Systematic Review and Meta-Analysis.
AB  - Dioxin-related compounds are associated with teratogenic and mutagenic risks in
      laboratory animals, and result in adverse pregnancy outcomes. However, there were
      inconsistent results in epidemiology studies. In view of this difference, we
      conducted a systematic review and meta-analysis to examine this association and
      to assess the heterogeneity among studies. Comprehensive literature searches were
      performed to search for relevant articles published in English up to 15 May 2012.
      In total, we identified 15 studies which included 9 cohort and 6 case control
      studies. The Cochrane Q test and index of heterogeneity (I(2)) were used to
      evaluate heterogeneity. In either cohort studies (I(2)=0.89, p<0.0001) or case
      control studies (I(2)=0.69, p=0.02), significant heterogeneity of risk estimates
      were observed. Subgroup analyses found no significant increased risk of adverse
      pregnancy outcome with air dioxin-related compounds exposure (RR=0.99, 95%
      CI:0.85-1.16), no significant increased risk of spontaneous abortion (SAB) with
      exposure to food dioxin-related compounds (RR=1.05, 95% CI:0.80-1.37), higher
      significant risks of low birth weight (LBW) with exposure to food dioxin-related
      compounds (RR=1.55, 95% CI:1.24-1.94), and higher significant risks of birth
      defects with maternal solid contaminants dioxin exposure (OR=1.24, 95% CI:1.19
      1.29). In conclusion, more evidences are needed to confirm the association
      between environmental dioxin-related compounds exposure and pregnancy outcome. 

PMID- 25780517
TI  - Pregnancy Complications and Neonatal Outcomes in Multiple Pregnancies: A
      Comparison between Assisted Reproductive Techniques and Spontaneous Conception.
AB  - BACKGROUND: This study compared neonatal outcome and maternal complications in
      multiple pregnancies after assisted reproductive technologies (ART) to
      spontaneous pregnancies. MATERIALS AND METHODS: In this cross-sectional study, we
      reviewed medical records of 190 multiple pregnancies and births conceived by ART
      or spontaneous conceptions between 2004 and 2009 in Women Hospital. Obstetric
      history and outcomes were recorded and compared between these two groups. SPSS
      version 13 was used for data analysis. The results were analyzed using student's
      t test, chi square and logistic regression (p<0.05). RESULTS: There were 106
      deliveries from spontaneous conceptions and 84 that resulted from ART. Parity
      history and mode of delivery significantly differed between the two groups
      (p<0.001). The ART group had significantly higher preterm labor and premature
      rupture of membranes (PROM) whereas pregnanc-induced hypertension (PIH) was
      higher in the spontaneous group (p=0.01). Newborn intensive care unit (NICU)
      admission, duration of hospitalization, still birth and low gestational age were
      significantly higher in the ART group while neonatal jaundice was higher in the
      spontaneous group. Logistic regression analysis by considering neonatal
      complications as the dependent variable showed that respiratory distress syndrome
      (RDS), NICU admission and Apgar score were independent predictors for neonatal
      complications. CONCLUSION: Obstetric and neonatal outcomes must be considered in
      multiple pregnancies conceived by ART.

PMID- 25780518
TI  - The Higher Response of Vascular Endothelial Growth Factor and Angiotensin-II to
      Human Chorionic Gonadotropin in Women with Polycystic Ovary Syndrome.
AB  - BACKGROUND: This research investigated the response of vascular active factors,
      vascular endothelial growth factor (VEGF) and angiotensin-II (AT-II) to ovarian
      stimulation during 24 hours in patients with polycystic ovary syndrome (PCOS).
      MATERIALS AND METHODS: In this clinical trial study, 52 patients with PCOS and 8
      control cases were stimulated with human chorionic gonadotropin (HCG) on the
      4(th) to 7(th) day of the patients' natural or induced menstrual cycles. We
      measured VEGF and AT-II by radioimmunoassay before the injection (0 hour) and 3,
      8, 12, 18 and 24 hours after the stimulation. RESULTS: After ovarian stimulation,
      there was substantially higher level of VEGF in typical PCOS patients than the
      other three groups at the 3 hour time point (p<0.05), while there were no
      significant differences in VEGF at all the other time points among the four
      groups. As for AT-II, before and at all time points after the ovarian
      stimulation, it seemed that the AT-II levels in patients' sera with different
      phenotypes of PCOS by the Rotterdam criteria were all higher than in the control
      group although the differences were not statistically significant. The level of
      AT-II in typical PCOS patients was also significantly higher than the other three
      groups at the 3 hour time point (p<0.05), while no significant differences at all
      the other time points among the four groups were observed. CONCLUSION: The
      response to the stimulation varied among patients with different phenotypes of
      PCOS according to the Rotterdam criteria. Serum VEGF and AT-II were possible
      contributors to an increased risk of developing ovarian hyperstimulation syndrome
      (OHSS) in patients with typical PCOS during the early follicular phase (3 hours)
      after ovarian stimulation ( REGISTRATION NUMBER: NCT02265861).

PMID- 25780519
TI  - The comparison between Intrauterine Insemination and Fallopian Tube Sperm
      Perfusion Using FAST(r)System in Patients with Unexplained Infertility.
AB  - BACKGROUND: Controlled ovarian stimulation (COH) with intrauterine insemination
      (IUI) is commonly offered to infertile couples with patent fallopian tubes
      because it is simple, non-invasive and cost-effective technique. Another non
      invasive method is fallopian tube sperm perfusion (FSP). This study was performed
      to compare the relative efficacy between FSP using fallopian sperm transfer
      (FAST) system and standard IUI in patients with unexplained infertility.
      MATERIALS AND METHODS: This prospective randomized study was conducted at the IVF
      Unit, Department of Gynecology and Obstetrics, Mazandaran University of Medical
      Sciences, Sari, Iran, from March 2011 to February 2012. A total of ninety
      patients with unexplained infertility underwent ovarian stimulation with
      clomiphene citrate and human menopausal gonadotropin (HMG). Patients were then
      randomly assigned into either group I (n=45) to undergo standard IUI or group II
      (n=45) to undergo FSP using FAST system. RESULTS: The patients' basic
      characteristics, including age, primary infertility and duration of infertility,
      were not significantly different between two study groups. In the group I, there
      were 9 pregnancies (a pregnancy rate per cycle of 20%), whereas in the group II,
      8 pregnancies occurred (a pregnancy rate per cycle of 17.8%, p>0.05). CONCLUSION:
      FSP using FAST system offers no advantage over the standard IUI in order to
      increase pregnancy rate in patients with unexplained infertility.

PMID- 25780520
TI  - Efficacy of Highly Purified Urinary FSH versus Recombinant FSH in Chinese Women
      over 37 Years Undergoing Assisted Reproductive Techniques.
AB  - BACKGROUND: Urine derived follicle-stimulating hormone (uFSH) contains a higher
      proportion of acidic isoforms, whereas recombinant FSH (rFSH) contains a higher
      proportion of less-acidic isoforms. Less-acidic isoforms have a faster clearance,
      and thus a shorter half-life than the acidic FSH isoforms. The slow clearance of
      the acidic isoforms has a longer half-life and higher biological activity. This
      study was designed to determine whether uFSH or rFSH is more effective in older
      Chinese women undergoing assisted reproductive techniques (ART). MATERIALS AND
      METHODS: This is a prospective, randomized, controlled cohort study. A total of
      508 Chinese women over 37 years were randomized into two following study groups
      for their in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI)
      cycles: i. group A (n=254) were treated with rFSH, and ii. group B (n=254) were
      treated with uFSH. Both groups were suppressed with a gonadotropin-releasing
      hormone (GnRH) analogue using a long down-regulation protocol. The main outcomes
      for comparison were days of stimulation, estradiol (E2) on the day of human
      chorionic gonadotropin (hCG) administration, number of oocytes collected, amount
      of FSH used, quantity of FSH/oocyte, endometrial thickness at hCG day, M P oocyte
      rate, 2PN zygote rate, grade I embryo rate, number of embryos cryopreserved,
      pregnancy rate, implantation rate, abortion rate and the rate of no transferable
      embryos. RESULTS: Twenty two cycles including 16 cycles with poor ovarian
      response and six cycles with ovarian hyperstimulation syndrome were cancelled.
      There were 243 cycles left in each group. The patients treated with uFSH had a
      significantly higher 2PN zygote rate (87.4 vs. 76.6%, p<0.001), grade I embryo
      rate (49.8 vs. 40.8%, p<0.001) and endometrial thickness on day of hCG (11.8 mm
      vs. 11.2 mm, respectively, p=0.006) and a lower rate of no transferable embryos
      (1.2 vs. 5.3%, p=0.019) than women treated with rFSH. The other measures
      evaluated showed no statistically significant differences between groups
      (p>0.05). CONCLUSION: This study showed that uFSH produced a significantly higher
      proportion of grade I embryos than rFSH in older Chinese women and there was a
      significantly lower chance of no transferable embryos in uFSH cycles. The
      clinical efficacy of the two gonadotropins was equivalent.

PMID- 25780521
TI  - The correlations of anti-mullerian hormone, follicle-stimulating hormone and
      antral follicle count in different age groups of infertile women.
AB  - BACKGROUND: The objective of our study was to identify the correlations between
      the tests currently used in ovarian reserve assessment: anti-Mullerian hormone
      (AMH), follicle stimulating hormone (FSH) and antral follicle count (AFC) and to
      distinguish the most reliable markers for ovarian reserve in order to select an
      adequate strategy for the initial stages of infertility treatment. MATERIALS AND
      METHODS: In this prospective study, 112 infertile women were assessed. Subjects
      were divided into three age groups: group I <35 years (n=39), group II 35-40
      years (n=31), and group III 41-46 years (n=42). AMH, FSH and AFC were determined
      on days 2-3 of the patients' menstrual cycles. RESULTS: There was a significantly
      elevated negative correlation between age and AMH level (rs=-0.67, p<0.0001) and
      AFC (rs=-0.55, p<0.0001). We observed a significantly positive correlation
      between age and FSH (rs=0.38, p<0.0001). AMH negatively correlated with FSH (rs=
      0.48, p<0.0001) and positively with AFC (r=-0.71, p=0.0001). There was a moderate
      negative relation between FSH and AFC (r=-0.41, p=0.0001) and moderate positive
      relation between age and FSH (rs=0.38, p<0.0001). The correlation analysis
      performed in separate groups showed that AMH and AFC showed a statistically
      significant positive correlation for group I (r=0.57, p<0.0001), group II
      (r=0.69, p<0.0001) and group III (r=0.47, p<0.002). A statistically significant
      correlation between FSH and AMH was detected only in groups I (r=-0.41, p<0.02)
      and II (r=-0.55, p<0.0001). A statistically significant correlation existed
      between FSH and AFC only in group III (r=-0.42, p<0.006), as well as between age
      and AFC only in group I (r=-0.35, p<0.03). CONCLUSION: Currently, AMH should be
      considered as the more reliable of the ovarian reserve assessments tests compared
      to FSH. There is a strong positive correlation between serum AMH level and AFC.
      The use of AMH combined with AFC may improve ovarian reserve evaluation.

PMID- 25780522
TI  - Do Endometrial Movements Affect The Achievement of Pregnancy during Intrauterine
      Insemination?
AB  - BACKGROUND: This study was aimed to assess the effect of endometrial movements on
      pregnancy achievement in intrauterine insemination (IUI) cycles. MATERIALS AND
      METHODS: The population of this observational study was composed of unexplained
      infertility couples undergoing first-time IUI with clomiphene citrate between
      September 2010 and October 2011. Not only endometrial movements, but also
      thickness, volume, pattern, and echogenic change of endometrium were analyzed
      prospectively in prediction of pregnancy. RESULTS: The total number of 241 cycles
      of IUI with 49 intrauterine pregnancies (20.3%) was analyzed. Pregnancy was not
      related to endometrial thickness and endometrial volume, but significantly
      related to endometrial movements associated with the number of contraction,
      strong movement, cervicofundal direction, and hyperechoic change (p<0.05).
      Pregnant group showed higher cervicofundal movement rate (89.8 vs. 75.5%).
      CONCLUSION: For IUI cycles stimulated by clomiphene citrate in unexplained
      infertility women, endometrial movements on the day of IUI could be a predictor
      of pregnancy.

PMID- 25780523
TI  - The Social Consequences of Infertility among Iranian Women: A Qualitative Study.
AB  - BACKGROUND: Infertility may prevent couples to achieve the desired social roles
      and lead to some social and psychological problems. This study aimed to explain
      the social consequences of infertility in Iranian women seeking treatment.
      MATERIALS AND METHODS: A qualitative content analysis was conducted based on 32
      semi-structured interviews with 25 women affected by primary and secondary
      infertility with no surviving children. The participants were purposefully
      selected with maximum variability from a fertility health research center in
      Tehran, Iran, from January to October 2012. Data were collected using semi
      structured interviews and analyzed using the conventional content analysis
      method. RESULTS: Our findings indicate that the consequences of infertility are
      divided into five main categories: 1. violence including psychological violence
      and domestic physical violence, 2. marital instability or uncertainty, 3. social
      isolation including avoiding certain people or certain social events and self
      imposed isolation from family and friends, 4. social exclusion and partial
      deprivation including being disregarded by family members and relatives and
      reducing social interactions with the infertile woman and 5. social alienation.
      CONCLUSION: This study reveals that Iranian women with fertility issues seeking
      treatment face several social problems that could have devastating effects on the
      quality of their lives. It is, therefore, recommended that, in Iran, infertility
      is only considered as a biomedical issue of a couple and pay further attention to
      its sociocultural dimensions and consequences.

PMID- 25780524
TI  - Outcomes of Micro-Dissection TESE in Patients with Non-Mosaic Klinefelter's
      Syndrome without Hormonal Treatment.
AB  - BACKGROUND: Klinefelter syndrome (KS) is the most common sex chromosomal disorder
      in males and historically patients have been labeled as sterile. After the
      introduction of microdissection testicular sperm extraction (micro-TESE),
      successful sperm retrievals for intracytoplasmic sperm injection (ICSI) have been
      reported. MATERIALS AND METHODS: A retrospective study was undertaken on ten
      patients with non-mosaic KS undergoing micro-TESE for ICSI. The testicular volume
      and FSH and LH levels of each patient were measured. Karyotypes were confirmed by
      analyzing peripheral lymphocyte metaphases. Physical examination of the external
      genitalia was performed in all patients to rule out any co-existing anomaly.
      Micro-TESE was performed in order to investigate the presence of seminiferous
      tubules which may contain spermatozoa. When testicular spermatozoa were found in
      micro-TESE, ICSI was performed. Embryos were evaluated for further development.
      Fertilization was considered to have occurred after the visualization of the two
      pro-nuclei stage of the oocyte 24 hours after the intracytoplasmic injection of
      the motile spermatozoa. Pregnancy was confirmed by visualization of an
      intrauterine gestational sac under ultrasonographic examination. RESULTS:
      Testicular biopsy revealed motile spermatozoa in 6 of 9 patients (66.6 %).
      Fertilization rate per embryo-transfer was 40%. One patient was able to conceive
      and fathered a healthy boy weights 3410 g at the 39(th) week of gestation.
      CONCLUSION: Retrieval of testicular spermatozoa by micro-TESE is possible for
      azoospermic men with KS when assisted reproductive techniques are applied. For
      patients with KS who want to conceive, assisted reproductive techniques (ART)
      should be recommended.

PMID- 25780525
TI  - The expression of the autophagy gene beclin-1 mRNA and protein in ectopic and
      eutopic endometrium of patients with endometriosis.
AB  - BACKGROUND: To investigate the expression of Beclin-1 mRNA and protein in eutopic
      and ectopic endometrium of women with and without endometriosis, and evaluate the
      association of Beclin-1 protein expression and serum CA125 levels in the
      endometriosis group due to CA125 being a well-known biomarker of endometriosis.
      MATERIALS AND METHODS: The expression levels (mean +/- SD) of the mRNA and
      protein of Beclin-1 were examined in uterine endometria from 26 women without
      endometriosis and in eutopic and ectopic endometria from 26 endometriosis
      patients through experimental study, as reverse transcription PCR and Western
      blotting assays. Serum CA125 levels in the endometriosis and control groups were
      compared and the correlation between Beclin-1 protein expression and serum CA125
      was evaluated in the endometriosis group. RESULTS: Both eutopic (0.12 +/- 0.04,
      1.25 +/- 0.42) and ectopic (0.12 +/- 0.05, 1.09 +/- 0.50) endometriotic tissue
      from 26 women with endometriosis expressed significantly lower levels of Beclin-1
      mRNA and protein than endometrium from 26 normal women (0.15 +/- 0.02, 1.67 +/-
      0.44) (p<0.05). Serum CA125 levels were found to be significantly higher in the
      endometriosis group (p<0.05). In addition, Beclin-1 protein expression of eutopic
      endometria in patients with endometriosis was negatively correlated with serum
      CA125 (r= -0.57, p<0.01). CONCLUSION: The present study strongly suggests that
      Beclin-1 may play a role in the formation and progression of endometriosis.

PMID- 25780526
TI  - The 763C>G Polymorphism of The Secretory PLA2IIa Gene Is Associated with
      Endometriosis in Iranian Women.
AB  - BACKGROUND: Endometriosis is a chronic gynecological disease resulting from
      complex interactions between genetic, hormonal, environmental and oxidative
      stress and intrinsic inflammatory components. The aim of this study was to
      investigate the potential association of the 763C>G polymorphism in the secretory
      phospholipase A2 group IIa gene (PLA2G2A) with the risk of endometriosis in
      Iranian women. MATERIALS AND METHODS: Ninety seven patients with endometriosis
      along with 107 women who were negative for endometriosis after laparoscopy and
      laparatomy, and served as the control group, were enrolled for this cross
      sectional study. Samples were genotyped using the polymerase chain reaction
      restriction fragment length polymorphism method. RESULTS: Multivariate analysis
      was used to examine the association between the risk of endometriosis and the
      763C>G polymorphism of PLA2G2A. Genotype distributions of PLA2G2A were
      significantly different between patients and the controls (p<0.001, OR=0.22, 95%
      CI=0.21-0.39). Correlation analysis showed that there was a significant
      association between the normal homozygous genotype and susceptibility to
      endometriosis (p<0.001). CONCLUSION: The present study suggests that the 763C>G
      polymorphism of PLA2G2A plays an important role as an independent factor in the
      risk of endometriosis in Iranian women.

PMID- 25780527
TI  - Expression and Distribution of Calcium-Binding Protein S100P in Human Placenta
      during Pregnancy.
AB  - BACKGROUND: S100P is a member of the S100 family of calcium-binding proteins, and
      it participates in pathophysiological events, such as tumor growth and invasion.
      Based on the striking similarities between trophoblast cells and tumor cells with
      regard to proliferative and invasive properties, we raised the question of
      whether and how S100P expresses in trophoblast cells during development. This
      study aimed to investigate the expression pattern of S100P in the human placenta
      during pregnancy development. MATERIALS AND METHODS: In this experimental study,
      we collected 16 first-trimester placental tissues, 10 second-trimester placental
      tissues, and 12 term placentas. The mRNA expression levels of S100P were detected
      by reverse-transcription-polymerase chain reaction (RT-PCR) and quantitative real
      time PCR, the protein expression levels were detected by western blot, and the
      localization of S100P was measured by immunohistochemical staining. The values
      obtained from PCR and western blot analysis were expressed as the mean +/- SD.
      Levene's test was used to test equal variances, and one-way analysis of variance
      (ANOVA) was used to evaluate differences between groups. RESULTS: Protein and
      mRNA expression of S100P could be detected in placenta during pregnancy, with
      minor higher levels in first-trimester (p>0.05). Immunohistochemical staining
      revealed that S100P protein was strongly expressed in syncytiotrophoblasts, and
      moderate expression was detected in villous cytotrophoblasts and cytotrophoblast
      columns. The S100P protein was localized to both cytoplasm and nuclei in
      syncytiotrophoblasts, while it only existed in the cytoplasm of cytotrophoblasts.
      CONCLUSION: S100P was strongly detected in human placenta during pregnancy. The
      specific expression and distribution of S100P in human placenta throughout
      gestation suggested that S100P function might vary with its location in the
      placenta.

PMID- 25780528
TI  - A novel large-scale deletion of the mitochondrial DNA of spermatozoa of men in
      north iran.
AB  - BACKGROUND: To investigate the level of correlation between large-scale deletions
      of the mitochondrial DNA (mtDNA) with defective sperm function. MATERIALS AND
      METHODS: In this analytic study, a total of 25 semen samples of the nor-
      mozoospermic infertile men from North of Iran were collected from the IVF center
      in an infertility clinic. The swim-up procedure was performed for the separation
      of spermatozoa into two groups; (normal motility group and abnormal motility
      group) by 2.0 ml of Ham's F-10 medium and 1.0 ml of semen. After total DNA
      extraction, a long-range polymerase chain reaction (PCR) technique was used to
      determine the mtDNA deletions in human spermatozoa. RESULTS: The products of PCR
      analysis showed a common 4977 bp deletion and a novel 4866 bp deletion (flanked
      by a seven-nucleotide direct repeat of 5?-ACCCCCT-3? within the deleted area)
      from the mtDNA of spermatozoa in both groups. However, the frequency of mtDNA
      deletions in abnormal motility group was significantly higher than the normal
      motility group (56, and 24% for 4866 bp-deleted mtDNA and, 52, and 28% for 4977
      bp-deleted mtDNA, respectively). CONCLUSION: It is suggested that large-scale
      deletions of the mtDNA is associated with poor sperm motility and may be a
      causative factor in the decline of fertility in men.

PMID- 25780529
TI  - Association between Maternal MTHFR Polymorphisms and Nonsyndromic Cleft Lip with
      or without Cleft Palate in Offspring, A Meta-Analysis Based on 15 Case-Control
      Studies.
AB  - BACKGROUND: The methylenetetrahydrofolate reductase (MTHFR) is thought to be
      involved in the development of nonsyndromic cleft lip with or without cleft
      palate (NSCL/P). However, conflicting results have been obtained when evaluating
      the association between maternal MTHFR C677T and A1298C polymorphisms and the
      risk of NSCL/P. In light of this gap, a meta-analysis of all eligible case
      control studies was conducted in the present study. MATERIALS AND METHODS: A
      total of 15 case-control studies were ultimately identified after a comprehensive
      literature search and Hardy-Weinberg equilibrium (HWE) examination. Cochrane's Q
      test and index of heterogeneity (I(2)) indicated no obvious heterogeneity among
      studies. RESULTS: Fixed or random-effects models were used to calculate the
      pooled odds ratios (ORs). The results showed that the TT genotype in mothers
      increased the likelihood of having NSCL/P offspring 1.25 times (95% CI: 1.047
      1.494) more than the CC homozygotes. Meanwhile, maternal TT genotype increased
      the risk of producing NSCL/P offspring in recessive model (OR=1.325, 95% CI:
      1.124-1.562). However, the CT heterozygote and the CT+TT dominant models had no
      association with NSCL/P offspring compared with the CC wild-type homozygote
      model. Subgroup analyses based on ethnicity indicated that maternal TT genotype
      increased the likelihood of having NSCL/P offspring in Whites (OR=1.308, 95% CI:
      1.059-1.617) and Asians (OR=1.726, 95% CI: 1.090-2.733) in recessive model. Also,
      subgroup analyses based on source of control showed that mothers with the 677TT
      genotype had a significantly increased susceptibility of having NSCL/P children
      in hospital based population (HB) when compared with CC homozygotes (OR=1.248,
      95% CI: 1.024-1.520) and un- der the recessive model (OR=1.324, 95% CI: 1.104
      1.588). Furthermore, maternal A1298C polymorphism had no significant association
      with producing NSCL/P offspring (dominant model OR=0.952, 95% CI: 0.816-1.111,
      recessive model OR=0.766, 95% CI: 0.567-1.036). CONCLUSION: MTHFR C677T
      polymorphism is associated with the risk of generating NSCL/P offspring, and
      being a 677TT homozygote is a risk factor. MTHFR A1298C polymorphism was not
      associated with generating NSCL/P offspring. However, further work should be
      performed to confirm these findings.

PMID- 25780530
TI  - Tuberculosis endometritis presenting as a leiomyoma.
AB  - Genitourinary tuberculosis is a common extrapulmonary manifestation of
      tuberculosis. Taking into consideration that genitourinary tuberculosis may be
      associated with a diversity of presentations, its diagnoses may be difficult. A
      young woman with an initial presumptive diagnosis of a uterine leiomyoma
      presented with abdominal pain and a pelvic mass that after further
      investigations, she was diagnosed with genital tuberculosis. 

PMID- 25780531
TI  - Methodological concerns regarding levels of vascular endothelial growth factor
      (VEGF) in serum of women with endometriosis.

PMID- 25780532
TI  - Effectiveness of mindfulness-based cognitive therapy on reduction of depression
      and anxiety symptoms in mothers of children with cancer.
AB  - BACKGROUND: Findings demonstrated that parents of children with cancer experience
      elevated levels of distress, depression, anxiety, posttraumatic stress symptoms,
      and subjective symptoms of stress. In this study, we determined effectiveness of
      Mindfulness-Based Cognitive Therapy (MBCT) on reduction of depression and anxiety
      symptoms in mothers of children with cancer. METHODS: Four mothers whose children
      had cancer were diagnosed to have depression and anxiety symptoms, using Beck
      Anxiety Inventory, Beck Depression Inventory II, and Structured Clinical
      Interview for DSM-IV. They were selected through purposeful sampling to
      participate in this experimental single-case study. After the baseline was
      determined, subjects attended an eight-session program of Mindfulness-Based
      Cognitive Therapy. RESULTS: The comparison of baseline and post-test showed that
      depression and anxiety symptoms decreased through MBCT. Improvement quotient for
      depression and anxiety of each subject was good. CONCLUSION: Data showed that
      MBCT reduced depression and anxiety symptoms in mothers of children with cancer.

PMID- 25780533
TI  - Sexuality after breast cancer: need for guideline.
AB  - BACKGROUND: Clinical experiences have revealed that patients with breast cancer
      experience various sexual problems following their treatment. Breast cancer
      negatively impacts the sexual life of the afflicted couples, and as a traumatic
      event can influence women's psychosexual functioning and intimate relationship.
      This review focuses on sexuality after breast cancer and on a growing need for
      bio-psycho-social guidelines for breast cancer treatment. METHODS: This study
      aims to review the literature on management, psychological outcomes and sexual
      dysfunction in patients with breast cancer. RESULTS: Although the benefits of the
      current treatment strategies are well established, many cancer survivors are at
      risk for developing psycho physiological symptoms including sexual dysfunction.
      Cancer and treatment-related factors can influence sexual functioning. We review
      current treatment-related side effects on sexual functioning such as desire,
      arousal and orgasm in breast cancer patients. Despite the impact of medical
      treatment on survival of patients with breast cancer, no satisfactory steps have
      been taken towards improving sexual functioning of these patients. CONCLUSION:
      Breast cancer affects many aspects of sexuality, including changes in physical
      functioning and in the perception of feminity. Sexual dysfunction following
      breast cancer should be diagnosed and managed as a systematic approach with
      multidisciplinary inputs. Healthcare professionals should assess the effects of
      medical and surgical treatment on the sexuality of breast cancer survivors.

PMID- 25780534
TI  - Production of human papilloma virus type 16 e6 oncoprotein as a recombinant
      protein in eukaryotic cells.
AB  - BACKGROUND: Cervical cancer is one of the most important and widespread cancer
      which affects women. There are several causes of cervical cancer; among them HPV
      types 16 and 18 are the most prominent ones which are recurrent and persistent
      infections. These genotypes are currently about 70% of cervical cancer causes in
      developing countries. Due to the importance of these viruses in cervical cancer,
      we pioneered the production of Human Papilloma Virus type16 E6 oncoprotein as a
      recombinant protein in order to develop a vaccine. Two HPV oncoproteins, E6 and
      E7, are consistently expressed in HPV-associated cancer cells and are responsible
      for malignant transformation. These oncogenic proteins represent ideal target
      antigens for developing vaccine and immunotherapeutic strategies against HPV
      associated neoplasm. METHODS: In the present study, the cloned E6-oncoprotein of
      HPV16 in pTZ57R/T-E6 vector was used to produce professional expression vector.
      The target gene was subcloned in a eukaryotic expression vector. The pcDNA3-E6
      vector was propagated in E.coli strain DH5alpha and transfected into CHO cells 72
      hours post-transfection. RESULTS: The transfected cells were harvested; mRNA
      detection and the interest protein production were confirmed by western blot
      analysis using specific anti E6 monoclonal antibody. CONCLUSION: HPV16-E6 target
      protein recognized by specific antibody could be an appropriate form of protein,
      which can be used for further studies. Due to potential effect of this protein,
      its DNA construction can be used for DNA vaccine in future studies.

PMID- 25780535
TI  - Human papilloma virus in head and neck squamous cell cancer.
AB  - BACKGROUND: Epidemiologic and molecular evidences have established a strong link
      between high risk types of Human Papilloma Virus and a subgroup of Head and Neck
      Squamous Cell Carcinomas (HNSCC). We evaluated the frequency of HPV positivity in
      HNSCC and its relationship to demographic and some risk factor variables in an
      open case- control study. METHODS: Fourteen recently diagnosed patients with
      squamous cell cancer of oropharynx, hypopharynx and larynx aged 18-50 years were
      examined from 2008-2010 in Tabriz, Iran. HPV DNA was extracted from paraffin
      embedded blocks of each patient's sample for PCR evaluation. Saliva samples of 94
      control cancer-free subjects were collected for DNA analysis. Multivariable
      logistic regression method was used to calculate odds ratio for case-control
      comparisons. RESULTS: High risk HPV was detected in 6(42.8%) patients, and
      6(5.3%) control subjects which was statistically significant (p<0.0001). HPV-18
      was the most frequent type both in the cases and controls. HPV-16 DNA was
      detected in two patients of the case group, but it was not detected in any of the
      controls. The relation between demographic and risk factor variables was not
      statistically significant. CONCLUSION: HPV infection has a significant impact on
      HNSCC. Despite HPV-16 stronger impact, HPV-18 is more likely to cause malignant
      degeneration in such cancers amongst some communities. It is vital to introduce
      and conduct immunization schedules in health care systems to protect communities
      to some extent.

PMID- 25780536
TI  - Screening of C-kit gene Mutation in Acute Myeloid Leukaemia in Northern India.
AB  - BACKGROUND: Acute Myeloid Leukaemia (AML) is a cancer of blood-forming cells in
      bone marrow. C-kit gene is a Receptor Tyrosine Kinase class III (RTK) that is
      expressed by early hematopoietic progenitor cells and plays an important role in
      hematopoietic stem cell proliferation, differentiation and survival. It is known
      that c-kit is a proto-oncogene and the activating c-kit mutations are likely to
      contribute in the development of leukaemia in humans. Exon 11 of c-Kit gene is
      the frequent site for mutations in different kinds of tumours. METHODS: In order
      to determine the frequency and prevalence of exon 11 mutations in 51 AML cases,
      we have done polymerase chain reaction-single-strand conformational polymorphism
      followed by direct DNA sequencing. RESULTS: The c-kit mutations in exon 11 were
      detected in 15.68% (8/51) in AML cases. We have detected totally ten missense
      mutations in eight AML cases those include Lys550Asn, Tyr568Ser, Ile571Leu,
      Tyr578Pro, Trp582Ser and Arg588Met and novel missense mutations at codons
      Ile563Lys and Val569Leu. Mutations at codons Ile571Leu and Trp582Ser was found in
      two independent cases. CONCLUSION: The presence of c-kit mutations in our study
      adds to investigative spectrum of AML cases. Since the c-kit mutations are seen
      in other malignancies, mutations in exon 11 of the c-kit gene might be involve in
      pathogenesis and represent useful predictive genetic marker in AML. Further
      studies in larger group of cases possibly will be required to determine the
      prognostic implications and to investigate how these mutations are co-related to
      the progression and pathogenesis of AML.

PMID- 25780537
TI  - Comparison of pap smear quality with anatomical spatula method and the common
      method (spatula-cytobrush): a single blind clinical trial.
AB  - BACKGROUND: Cervical cancer is the third most common cancer in women in the
      world. Papanicolaou smear is known as a standard test for cervical cancer
      screening; however, the most important challenge is high rates of false negative
      results. The aim of this study was to compare the quality of smears obtained by
      anatomical spatula and spatula-cytobrush. The most important factor in false
      negative result is inappropriate tool of sampling. METHODS: One hundred married
      women participated in this single blind clinical trial. All participants were
      interviewed; two samples were obtained from every participant: one with spatula
      cytobrush and another one with anatomical spatula. All slides were encoded and
      were assessed by two pathologists. Then, data were analyzed by means of kappa
      coefficient. RESULTS: Cell adequacy was 96.1 % in anatomical spatula method and
      91.2 % in spatula-cytobrush method (p= 0.016). The rates for endocervical cells
      and metaplasia cells in anatomical spatula method were 70.6% and 24.5%
      respectively and these amounts were 69.6% and 24.5% respectively in the spatula
      cytobrush method (p <0.001). No one reported any pain and the amount of bleeding
      was 38.2% in both methods (P>0.05). Regarding infection and inflammatory
      reactions there was no statistically significant difference between two methods
      (p>0.05). CONCLUSION: Based on our findings in this study, results of sampling
      with anatomical spatula method were more acceptable and better than those with
      spatula-cytobrush sampling.

PMID- 25780538
TI  - A study of 63 cases of mouth neoplasms in arecanut growing belt of sullia.
AB  - BACKGROUND: Betel nut and betel quid chewing are from major etiological factor
      for oral cancer. They also increase the risk of systemic diseases such as asthma,
      diabetes mellitus, metabolic syndrome, myocardial infarction, hypertension, and
      other cardiovascular diseases. METHODS: Sixty three patients of oral cancer in
      our institution during Jan. 2007 to May 2011 were included in our study. This
      study included 14 cases of lip carcinoma, 41 cases of buccal mucosa carcinoma, 7
      cases of tongue carcinoma, and 1 case of carcinoma of upper alveolus. Duration of
      use of betel quid, pan masala, and gutkha were studied as well as management.
      RESULTS: All patients in our study have been chewing betel-quid for 6-31 years
      (mean19.42 years). All of them quit betel quid and used easily available
      panmasala and gutkha for 4-13 years (mean 8.28 years). Nine cases of lip
      carcinoma, 13 cases of buccal mucosa carcinoma and 3 cases of tongue carcinoma
      were treated with surgery. Seven cases of lip carcinoma, 30 cases of buccal
      mucosa carcinoma and 5 cases of tongue carcinoma were treated with post operative
      or palliative radiotherapy. CONCLUSION: Betel nut chewing with or without tobacco
      and lime are proven to be carcinogens in human. Direct relationship between oral
      cancer and betel quid, gutkha, and panmasala use has been shown in our study. As
      betel quid, panmasala and gutkha chewing were proven to be carcinogens, a
      permanent ban on manufacturing and sale of these products should be implemented.

PMID- 25780539
TI  - Non surgical treatment of sacral osteosarcoma.
AB  - Osteosarcoma may rarely originate from the axial bones such as pelvis or
      vertebrae. In some pelvic and most vertebral primary tumors, resection often is
      not possible completely. In general, these tumors cannot be resected with
      negative margins so they need additional radiotherapy and chemotherapy, but
      results are unfavourable because of poor local control and high incidence of
      distant metastases. This is a case report of sacral osteosarcoma which was
      treated successfully with chemotherapy and radiation therapy. The patient is a 14
      year-old boy with a large osteosarcoma tumor in the first sacral vertebral body,
      with extra skeletal extension. The patient took radiotherapy (6000 centigray)
      plus chemotherapy regimen consisting of doxorubicin and cisplatin. In the last
      follow up 48 months later, the patient was completely asymptomatic with normal
      performance and there was not any evidence of local progression or distant
      metastasis. 

PMID- 25780540
TI  - Early sonographic diagnosis of neurocutaneous melanosis in a newborn.
AB  - Neurocutaneous melanosis (NCM) is a rare, congenital non-hereditary syndrome,
      characterized by multiple pigmented nevi. We report the radiologic findings of a
      newborn who had extensive cutaneous melanotic nevus with satellite lesions in the
      brain. Ultrasound showed multiple echogenic foci in the cerebral parenchyma.
      Subsequent MRI confirmed these lesions as characteristic deposits of melanin. The
      infant was asymptomatic, but presence of risk factors such as malign
      transformation or neurological manifestations makes early diagnosis very
      important. We present this case to emphasize on the radiological findings of this
      syndrome in order to reach an early diagnosis. 

PMID- 25780541
TI  - Randomized double-blind clinical trial of eutectic mixture of local anesthetic
      creams in reducing pain during hysterosalpingography.
AB  - BACKGROUND: Hysterosalpingography (HSG) is considered as a primary test in
      infertility work up worldwide due to its reliability in evaluating abnormalities
      related to the uterus and fallopian tubes. OBJECTIVES: To assess the efficacy of
      applying eutectic mixture of local anesthetics (lidocaine-prilocaine cream)
      (EMLA) on the uterine cervix in reducing pain during HSG. PATIENTS AND METHODS:
      Eighty patients undergoing HSG as part of infertility evaluation were randomly
      allocated to groups receiving either EMLA (N = 40) or placebo cream (N = 40) in a
      double-blinded prospective study. Fifteen minutes before HSG, 5 grams of 5% cream
      was applied to the uterine cervix using a cervical applicator. The degree of pain
      experienced by the patient was evaluated during and after HSG at five predefined
      steps on a visual analogue scale (VAS). RESULTS: There was no significant
      difference in the efficacy between EMLA and placebo creams in pain perception
      during the entire procedure. There was no significant difference in long term
      pain perception half an hour after the HSG performance. CONCLUSIONS: This study
      does not support the use of EMLA for HSG.

PMID- 25780542
TI  - Chondroblastoma of the navicular bone.
AB  - This is a case report of a 24-year-old man who presented with increased pain and
      firm swelling of the right foot after a minor twisting injury. Radiography,
      computed tomography (CT) and magnetic resonance imaging (MRI) findings showed
      ancillary information that was helpful for surgical treatment. The final
      diagnosis was confirmed as chondroblastoma of the navicular bone based on the
      pathology report. The navicularbone is a very rare site in the foot, where we
      should pay attention to chondroblastoma. 

PMID- 25780543
TI  - Bilateral supernumerary kidney: a very rare presentation.
AB  - To our knowledge, bilateral supernumerary kidney is a very rare renal abnormality
      and there are five cases presented in the literature. It is difficult to diagnose
      supernumerary kidney and clinicians have not detected most cases preoperatively.
      Laboratory and imaging studies were acquired and carefully examined. The normal
      laboratory tests were found. Emergency ultrasonography was performed and they
      revealed no signs of parenchymal abnormality in both kidneys. Serial imaging
      study including enhanced computed tomography (CT) was performed. An imaging study
      identified bilateral supernumerary kidney with expanded collecting systems. On
      each side, significant rotation anomaly was found. In addition, there were two
      different renal arteries originating from the aorta. This report presents
      radiological determinations of supernumerary kidney bilaterally in a young man.
      We think that CT commonly appears to be enough for the diagnosis of supernumerary
      kidneys. 

PMID- 25780544
TI  - A Comparison of the Performance of Myocardial Videodensitometry, Tissue Velocity
      Imaging and Tissue Tracking in Discrimination Between ST-Segment Elevation
      Ischemic Reperfusion Injury and Normal Reperfusion State After Non-Beating
      Cardiac Operation.
AB  - BACKGROUND: The timely diagnosis of presence or absence of reperfusion injury
      after cardiac operation is critical for the patient's outcome. Whether
      transesophageal echocardiography (TEE) acquisition of regional grayscale
      intensity (TI), velocity, and displacement (D) after cardiac operation can
      discriminate between patients with ST-segment elevation ischemic reperfusion
      injury (STEIRI) and normal reperfusion state remains unknown. OBJECTIVES: In this
      study, we investigated whether these parameters can effectively reflect the
      situation of ST-segment elevation ischemic reperfusion injury (STEIRI) in
      patients after cardiac operation and which has a higher performance of
      discrimination between patients with and without STEIRI. PATIENTS AND METHODS:
      The maximal and minimal grayscale intensity in the cardiac cycle [TI (max), TI
      (min)], the difference of TI (max) and TI (min) [TI (max-min)], the cyclic
      variation index of TI [TI (CVI)], the systolic velocity (Vs), the early diastolic
      velocity (Ve), the late diastolic velocity (Va) and the peak displacement in the
      cardiac cycle (D) at the lateral side of the mitral annulus were measured and
      compared between patients with and without STEIRI. The performance of these
      parameters in discriminating between patients with and without STEIRI was
      analyzed. RESULTS: Compared with the patients without STEIRI, the patients with
      STEIRI had significantly smaller TI (max-min), TI (CVI), Vs, Ve, Va and D
      (P<0.05). With the use of these parameters as the criteria to distinguish
      patients with STEIRI from patients without STEIRI, the areas under the receiver
      operating characteristic curve were 0.86 for TI (max-min), 0.99 for TI (CVI),
      0.89 for Vs, 0.71 for Ve, 0.85 for Va and 0.82 for D. For the best cut-off value
      of TI (CVI) of less than 34.45%, the sensitivity, specificity and accuracy for
      the prediction of patients with STEIRI were 94.74%, 97.05%, and 96.22%,
      respectively. CONCLUSION: The myocardial grayscale intensity, velocity and
      displacement can effectively reflect the situation of STEIRI in patients after
      cardiac operation, and TI (CVI) has a higher performance in discriminating
      between patients with and without STEIRI.

PMID- 25780545
TI  - Comparison of chest x-ray findings of smear positive and smear negative patients
      with pulmonary tuberculosis.
AB  - BACKGROUND: Tuberculosis is a chronic pulmonary infectious disease that has
      affected one-third of the people in the world. It causes nine million new cases
      and two million deaths per year. Chest radiography associated with Ziehl-Neelsen
      acid-fast staining procedure significantly helps the diagnosis of pulmonary
      tuberculosis (PTB). Chest radiography can help the diagnosis of tuberculosis in
      patients with a negative smear sample result that is mainly diagnosed with delay.
      OBJECTIVES: In this study, chest X-ray findings of PTB were compared in two
      groups of smear positive and smear negative patients. PATIENTS AND METHODS: In
      this retrospective descriptive-analytical study, 376 patients who had been
      confirmed with PTB were referred to Birjand Health Care Center from 2001 to 2006.
      Out of the 376 patients, 100 patients with a positive smear based on WHO criteria
      were selected. In addition, among negative smear patients, 100 were selected in
      whom similar demographic characteristics with positive smear patients were seen.
      All of them had undergone chest radiographies that were then interpreted by two
      expert radiologists independently. Moreover, all patients' sputa were examined by
      an expert laboratory technician at the reference laboratory of the health center.
      The obtained data were analyzed by means of frequency distribution table and
      descriptive statistics using SPSS (version 15) and Chi-square statistical test.
      RESULTS: Except reticulo-nodular infiltration, the relative frequency of other
      radiographic findings in positive smear patients were more than negative smear
      patients; and only differences in calcification variables, mediastinal widening,
      patchy infiltration and hilar adenopathy were statistically significant (P <
      0.05). CONCLUSIONS: Based on the results of this study, although radiographic
      findings are not diagnostic in PTB, they are helpful if the assessment associates
      with the view of clinical manifestations and sputum smears.

PMID- 25780546
TI  - Presence or absence of palmaris longus and fifth superficial flexor digitorum; is
      there any effect on median nerve surface area in wrist sonography.
AB  - BACKGROUND: Carpal tunnel syndrome (CTS) describes a set of symptoms caused by
      compression of the median nerve in the wrist, which is the most common site of
      nerve compression in the upper limb. This syndrome is a primary source of pain
      and reduced function in these patients, and the cause is compression of the
      median nerve where it passes beneath the flexor retinaculum in the wrist.
      OBJECTIVES: The aim of the present cross sectional study is to assess the absence
      of palmaris longus and fifth superficial flexor digitorum tendon as normal
      anatomic variations on the sonographic measurement of median nerve surface area
      in healthy individuals' wrists. PATIENTS AND METHODS: Ninety-three healthy
      volunteers underwent clinical evaluation for determining the presence of tendons
      in both wrists and sonographic measurement of median nerve surface area. RESULTS:
      In 41 of 186 (22%) hands, the palmaris longus tendon was absent and absence of
      the fifth flexor digitorum tendon was noted in eight (4.30 %). The median surface
      area in the hands without palmaris longus was meaningfully lower than the hands
      with it (P = 0.025), while the difference in the median surface area was not
      statistically significant with regard to presence of the fifth flexor digitorum
      tendon (P = 0.324). CONCLUSIONS: Based upon the findings of the present study, it
      seems that the median surface area as a sonographic finding is probably related
      to presence or absence of the palmaris longus tendon, so that hands with the
      tendon present have larger surface areas. In addition, it seems that this
      sonographic finding does not depend on the function of the fifth superficial
      flexor digitorum tendon. Therefore, no correlation between CTS and the presence
      of palmaris longus tendon should be observed.

PMID- 25780547
TI  - The minimum percentage of triolein emulsion for studying cerebral vascular
      permeability with least brain edema.
AB  - BACKGROUND: Triolein emulsion infusion into the brain produces transiently
      increased vascular permeability. OBJECTIVES: The purpose of this study was to
      find the minimum percentage of triolein emulsion required for studying vascular
      permeability with minimal brain edema. MATERIALS AND METHODS: Sixty healthy cats
      were divided into six groups according to the concentration of emulsified
      triolein infused into the carotid artery: group 1, 0.125% (n = 10); group 2,
      0.25% (n = 10); group 3, 0.5% (n = 10); group 4, 1% (n = 10); group 5, 2% (n =
      10); and group 6, saline infusion (control group, n = 10). T2-, T1- and contrast
      enhanced T1-weighted MR images were obtained 2 hours after infusing triolein
      emulsion. Contrast enhancement ratios (CERs) and signal intensity ratios (SIRs)
      versus contralateral hemispheres were calculated. Statistical analysis was
      performed by analysis of variance followed by Tukey's test. P values of <= 0.05
      were considered significant. RESULTS: The lesion hemispheres showed mild
      hyperintensity due to edema on T2-weighted images, and contrast enhancement on
      post-contrast T1-weighted images in cats of group 1-5. CERs showed statistically
      significant differences between the control group and group 3 (P = 0.006), group
      4 (P = 0.003), and group 5 (P < 0.001). However, SIRs were significantly
      different between the control group and group 5 only (P < 0.001). CONCLUSION: The
      minimum concentration of triolein emulsion required to increase vascular
      permeability adequately with minimal brain edema in a cat model was 0.5%.

PMID- 25780548
TI  - Better visualization of vermiform appendix with tissue harmonic imaging compared
      to conventional sonography.
AB  - BACKGROUND: Surgery of appendicitis carries 7-11% negative appendectomy rates.
      Sonographically visualized normal appendix precludes unnecessary computed
      tomography (CT) examination and may reduce negative appendectomy rates. Tissue
      harmonic imaging (THI) has been reported to improve the overall image quality.
      OBJECTIVE: We aimed to assess whether THI is more successful than conventional
      ultrasonography (US) in detecting normal and pathologic appendices. PATIENTS AND
      METHODS: The study was performed on 185 patients who applied for routine US
      examinations in whom clinical findings of appendicitis were detected in 25. We
      searched for the appendix; applying both THI and conventional US to each patient,
      one before and the other after the routine US examinations. Patients were divided
      into two groups; one was evaluated first with conventional US and the other first
      with THI. When the appendix was found, localization, diameter and time spent for
      visualization were recorded. Twelve patients were operated; all of whom had
      appendicitis pathologically. Two methods were compared for: 1. Success rates in
      all patients; female, male and child groups separately; 2. Visualization of
      pathologic and normal appendices; 3. Time for visualization of appendix; 4.
      Comparison of success rates in the adult and child population. The relationship
      between the rate of visualization and body mass index was evaluated. RESULTS: The
      appendix was visualized better by THI in all patients, and in the female and male
      groups (P < 0.001). In children, both methods were more successful compared to
      adults (P < 0.001, compared to male group, P < 0.001, compared to female group),
      with no difference between the methods (P = 0.22). When only the normal
      appendices were concerned, there was significant difference between both methods
      (P < 0.000). Both methods detected pathologic appendices better than normal ones,
      with a higher ratio for THI (P = 0.022 for the THI group, and chi(2) = 7.22, P =
      0.07 for the conventional US group). THI visualized the appendix faster. Both
      methods were more successful in lean patients (P = 0.004 for THI, P = 0.001 for
      conventional US imaging). CONCLUSIONS: THI visualizes appendix better than
      conventional US. It is a simple and time saving method that may eliminate further
      diagnostic imaging, and it may decrease negative appendectomy rates and related
      complications.

PMID- 25780549
TI  - A Review on the Paper Entitled: "The Cost-Utility Analysis of PET-Scan in the
      Diagnosis and Treatment of Non-Small Cell Lung Carcinoma in Iran.

PMID- 25780550
TI  - Unusual cortical bone features in a patient with gorlin-goltz syndrome: a case
      report.
AB  - Gorlin-Goltz syndrome (GGS) consists of ectodermal and mesodermal abnormalities.
      In this case report we will investigate lower extremity lesions of GGS. A 52-year
      old man with GGS underwent skull and lower extremity computer tomography.
      Radiographic findings included cervical spondylosis, transparent areas with
      slurred margins, and cerebral falx calcification. Tibial and fibular specific
      cortical lesions (thin cortical and subcortical cystic lesions) were seen on the
      radiography, which was confirmed by computer tomography. To our knowledge, this
      is the first report of such a long lesion of the tibia and fibula. Specific lower
      extremity cortical lesions (thin cortical and subcortical cystic lesions) may
      occur and these abnormalities can be found on radiography or CT, which are most
      probably attributed to retinoid treatment. 

PMID- 25780551
TI  - Diagnostic Evaluation of Neonatal Cholestasis: HIDA Scan and Alagille Criteria.

PMID- 25780552
TI  - The importance of standardizing acquisition settings and interpretation criteria
      of radionuclide cisternography.

PMID- 25780553
TI  - The association of GPR85 with PSD-95-neuroligin complex and autism spectrum
      disorder: a molecular analysis.
AB  - BACKGROUND: Autism spectrum disorder (ASD) has a complex genetic etiology. Some
      symptoms and mutated genes, including neuroligin (NLGN), neurexin (NRXN), and SH3
      and multiple ankyrin repeat domains protein (SHANK), are shared by schizophrenia
      and ASD. Little is known about the molecular pathogenesis of ASD. One of the
      possible molecular pathogenesis is an imbalance of excitatory and inhibitory
      receptors linked with the NLGN-PSD-95-SHANK complex via postsynaptic density
      protein/Drosophila disc large tumor suppressor/zonula occludens-1 protein (PDZ)
      binding. In the present study, we focused on GPR85 as a candidate gene for ASD
      because the C-terminal amino acid sequence of GPR85 [Thr-Cys-Val-Ile (YCVI)] is
      classified as a type II PDZ-binding motif, and GPR85 is a risk factor for
      schizophrenia. GPR85 is an orphan receptor that regulates neural and synaptic
      plasticity and modulates diverse behaviors, including learning and memory. While
      searching for molecules that associate with GPR85, we found that GPR85 was
      associated with postsynaptic density protein (PSD)-95 linked with NLGN in the
      brain. METHODS: We examined the proteins that associate with the C-terminal
      sequence of GPR85 by pull-down assay and immunoblot analysis and searched for a
      mutation of the GPR85 gene in patients with ASD. We used immunostaining to
      examine the intracellular localization of mutated GPR85 and its influence on the
      morphology of cells and neurons. RESULTS: The C-terminal sequence of GPR85
      interacted with PSD-95 at PDZ1, while NLGN interacted with PSD-95 at PDZ3. Two
      male patients with ASD from independent Japanese families possessed inherited
      missense mutations at conserved sites in GPR85: one had T1033C (M152T) and the
      other had G1239T (V221L). These mutations were located in a domain related to G
      protein interaction and signal transduction. In contrast to wild-type GPR85,
      mutated GPR85 was more preferentially accumulated, causing endoplasmic reticulum
      stress, and disturbed the dendrite formation of hippocampal neurons. CONCLUSIONS:
      GPR85 associated with the PSD-95 linked with NLGN, which is related to ASD. GPR85
      carrying the mutations detected in ASD patients disturbed dendrite formation that
      could be the candidate for molecular pathogenesis of ASD through the associated
      NLGN-PSD-95 receptor complex.

PMID- 25780554
TI  - Simultaneously estimating evolutionary history and repeated traits phylogenetic
      signal: applications to viral and host phenotypic evolution.
AB  - Phylogenetic signal quantifies the degree to which resemblance in continuously
      valued traits reflects phylogenetic relatedness. Measures of phylogenetic signal
      are widely used in ecological and evolutionary research, and are recently gaining
      traction in viral evolutionary studies. Standard estimators of phylogenetic
      signal frequently condition on data summary statistics of the repeated trait
      observations and fixed phylogenetics trees, resulting in information loss and
      potential bias. To incorporate the observation process and phylogenetic
      uncertainty in a model-based approach, we develop a novel Bayesian inference
      method to simultaneously estimate the evolutionary history and phylogenetic
      signal from molecular sequence data and repeated multivariate traits. Our
      approach builds upon a phylogenetic diffusion framework that model continuous
      trait evolution as a Brownian motion process and incorporates Pagel's lambda
      transformation parameter to estimate dependence among traits. We provide a
      computationally efficient inference implementation in the BEAST software package.
      We evaluate the synthetic performance of the Bayesian estimator of phylogenetic
      signal against standard estimators, and demonstrate the use of our coherent
      framework to address several virus-host evolutionary questions, including
      virulence heritability for HIV, antigenic evolution in influenza and HIV, and
      Drosophila sensitivity to sigma virus infection. Finally, we discuss model
      extensions that will make useful contributions to our flexible framework for
      simultaneously studying sequence and trait evolution.

PMID- 25780555
TI  - Effects of age and sex on cerebrovascular function in the rat middle cerebral
      artery.
AB  - BACKGROUND: Although the mechanisms underlying the beneficial effects of estrogen
      on cerebrovascular function are well known, the age-dependent deleterious effects
      of estrogen are largely unstudied. It was hypothesized that age and sex interact
      in modulating cerebrovascular reactivity to vasopressin (VP) by altering the role
      of prostanoids in vascular function. METHODS: Female (F) Sprague-Dawley rats
      approximating key stages of "hormonal aging" in humans were studied:
      premenopausal (mature multigravid, MA, cyclic, 5-6 months) and postmenopausal
      (reproductively senescent, RS, acyclic, 10-12 months). Age-matched male (M) rats
      were also studied. Reactivity to VP (10(-12)-10(-7) M) was measured in
      pressurized middle cerebral artery segments in the absence or presence of
      selective inhibitors of COX-1 (SC560, SC, 1 MUM) or COX-2 (NS398, NS, 10 MUM). VP
      stimulated release of PGI2 and TXA2 were measured using radioimmunoassay of 6
      keto-PGF1alpha and TXB2 (stable metabolites, pg/mg dry wt/45 min). RESULTS: In M,
      there were no changes in VP-induced vasoconstriction with age. Further, there
      were no significant differences in basal or in low- or high-VP-stimulated PGI2 or
      TXA2 production in younger or older M. In contrast, there were marked differences
      in cerebrovascular reactivity and prostanoid release with advancing age in F.
      Older RS F exhibited reduced maximal constrictor responses to VP, which can be
      attributed to enhanced COX-1 derived dilator prostanoids. VP-induced
      vasoconstriction in younger MA F utilized both COX-1 and COX-2 derived
      constrictor prostanoids. Further, VP-stimulated PGI2 and TXA2 production was
      enhanced by endogenous estrogen and decreased with advancing age in F, but not in
      M rats. CONCLUSIONS: This is the first study to examine the effects of age and
      sex on the mechanisms underlying cerebrovascular reactivity to VP. Interestingly,
      VP-mediated constriction was reduced by age in F, but was unchanged in M rats.
      Additionally, it was observed that selective blockade of COX-1 or COX-2 produced
      age-dependent changes in cerebrovascular reactivity to VP and that VP-stimulated
      PGI2 and TXA2 production were enhanced by endogenous estrogen in younger F. A
      better understanding of the mechanisms by which estrogen exerts its effects may
      lead to new age- and sex-specific therapeutic agents for the prevention and/or
      treatment of cerebrovascular diseases.

PMID- 25780556
TI  - NIH initiative to balance sex of animals in preclinical studies: generative
      questions to guide policy, implementation, and metrics.
AB  - In May of 2014, the NIH Director together with the Director of the Office of
      Research on Women's Health announced plans to take a multi-dimensional approach
      to address the over reliance on male cells and animals in preclinical research.
      The NIH is engaging the scientific community in the development of policies to
      improve the sex balance in research. The present, past, and future presidents of
      the Organization for the Study of Sex Differences, in order to encourage
      thoughtful discussion among scientists, pose a series of questions to generate
      ideas in three areas: 1. research strategies, 2. educational strategies, and 3.
      strategies to monitor effectiveness of policies to improve the sex balance in
      research. By promoting discussion within the scientific community, a consensus
      will evolve that will move science forward in a productive and effective manner. 

PMID- 25780557
TI  - Effects of sex chromosome dosage on corpus callosum morphology in supernumerary
      sex chromosome aneuploidies.
AB  - BACKGROUND: Supernumerary sex chromosome aneuploidies (sSCA) are characterized by
      the presence of one or more additional sex chromosomes in an individual's
      karyotype; they affect around 1 in 400 individuals. Although there is high
      variability, each sSCA subtype has a characteristic set of cognitive and physical
      phenotypes. Here, we investigated the differences in the morphometry of the human
      corpus callosum (CC) between sex-matched controls 46,XY (N =99), 46,XX (N =93),
      and six unique sSCA karyotypes: 47,XYY (N =29), 47,XXY (N =58), 48,XXYY (N =20),
      47,XXX (N =30), 48,XXXY (N =5), and 49,XXXXY (N =6). METHODS: We investigated CC
      morphometry using local and global area, local curvature of the CC boundary, and
      between-landmark distance analysis (BLDA). We hypothesized that CC morphometry
      would vary differentially along a proposed spectrum of Y:X chromosome ratio with
      supernumerary Y karyotypes having the largest CC areas and supernumerary X
      karyotypes having significantly smaller CC areas. To investigate this, we defined
      an sSCA spectrum based on a descending Y:X karyotype ratio: 47,XYY, 46,XY,
      48,XXYY, 47,XXY, 48,XXXY, 49,XXXXY, 46,XX, 47,XXX. We similarly explored the
      effects of both X and Y chromosome numbers within sex. Results of shape-based
      metrics were analyzed using permutation tests consisting of 5,000 iterations.
      RESULTS: Several subregional areas, local curvature, and BLDs differed between
      groups. Moderate associations were found between area and curvature in relation
      to the spectrum and X and Y chromosome counts. BLD was strongly associated with X
      chromosome count in both male and female groups. CONCLUSIONS: Our results suggest
      that X- and Y-linked genes have differential effects on CC morphometry. To our
      knowledge, this is the first study to compare CC morphometry across these
      extremely rare groups.

PMID- 25780558
TI  - A practical approach to vitamin and mineral supplementation in food allergic
      children.
AB  - BACKGROUND: The management of food allergy in children requires elimination of
      the offending allergens, which significantly contribute to micronutrient intake.
      Vitamin and mineral supplementation are commonly suggested as part of dietary
      management. However a targeted supplementation regime requires a complete
      nutritional assessment, which includes food diaries. Ideally these should be
      analysed using a computerised program, but are very time consuming. We therefore
      set out to evaluate current practice of vitamin and mineral supplementation in a
      cohort of children with non-Immunoglobulin E (IgE) mediated food allergies.
      METHODS: This prospective, observational study recruited children aged 4 weeks -
      16 years, who required to follow an elimination diet for non-IgE mediated
      allergies. Only children that improved according to a symptom score and were on a
      vitamin and/or mineral supplement were included. A 3-day food diary including
      vitamin and mineral supplementation was recorded and analysed using Dietplan
      computer program. We assessed dietary adequacy with/without the supplement using
      the Dietary Reference Values. RESULTS: One hundred-and-ten children had completed
      food diaries and of these 29% (32/110) were taking vitamin and/or mineral
      supplements. Children on hypoallergenic formulas were significantly (p = 0.007)
      less likely to be on supplements than those on alternative over-the-counter
      milks. Seventy-one percent had prescribable supplements, suggested by a
      dietitian/physician. Sixty percent of those without a vitamin supplement had a
      low vitamin D intake, but low zinc, calcium and selenium was also common. Of the
      supplemented cohort many continued to be either under or over-supplemented.
      CONCLUSION: This study has raised the question for the first time, whether
      clinicians dealing with paediatric food allergies should consider routine vitamin
      and/or mineral supplements in the light of deficient intake being so common in
      addition to being so difficult to predict.

PMID- 25780559
TI  - How can we assess the burden of muscle, bone and joint conditions in rural
      Botswana: context and methods for the MuBoJo focused ethnography.
AB  - BACKGROUND: Musculoskeletal diseases are the most common causes of long-term pain
      and disability worldwide and a growing international public health concern.
      However, the everyday burden and impact of musculoskeletal conditions are not
      well understood, especially among people living in low- and middle-income
      countries in Africa. Since 2011, World Spine Care, a nongovernmental
      organisation, has collaborated with the Botswana Ministry of Health to open spine
      care centres and to conduct research. The broad aim of the Muscle, Bone and Joint
      (MuBoJo) research project is to examine the sociocultural, organisational and
      clinical characteristics for the burden of living with and caring for people
      living with musculoskeletal conditions in rural Botswana. In this paper, we
      describe the community context, theoretical framework, and research methods to
      address the project aim with a qualitative study. METHODS/DESIGN: This focused
      ethnography is based on eight months (November 2011, April 2013, October 2013
      March 2014) of fieldwork in Botswana. The project was theoretically informed by
      the concepts of explanatory models of illness, social suffering, and biographical
      disruption. Data collection included fieldnotes, non-participant and participant
      observations, and informal and in-depth interviews with villagers and healthcare
      providers. Villager interviews were typically conducted in Setswana with an
      interpreter. Audio recordings were transcribed verbatim in the language spoken
      with Setswana contextually translated into English. Computer software supported
      qualitative data management. Analysis is ongoing using constant comparison and a
      template organising style to facilitate pattern-finding and reveal insights for
      the burden and care of musculoskeletal conditions. DISCUSSION: Findings from the
      MuBoJo Project will document the context of musculoskeletal burden, illness
      beliefs, self-care behaviours, and healthcare options in a Botswana rural
      village. These data will inform ongoing efforts to establish spine care clinics
      for underserved populations in low-middle income countries and sustain these
      healthcare services through local providers and volunteer health professionals.
      This study also will generate new knowledge about the burden and impact of
      muscle, bone and joint disorders for cross-cultural comparisons and patient
      centred interventions. CONCLUSIONS: Our systematic and transparent methodology to
      conduct musculoskeletal research in more than one language and in a cross
      cultural setting may be useful for investigators and NGO healthcare personnel.

PMID- 25780560
TI  - ETV2 expression increases the efficiency of primitive endothelial cell derivation
      from human embryonic stem cells.
AB  - BACKGROUND: Endothelial cells line the luminal surface of blood vessels and form
      a barrier between the blood and other tissues of the body. Ets variant 2 (ETV2)
      is transiently expressed in both zebrafish and mice and is necessary and
      sufficient for vascular endothelial cell specification. Overexpression of this
      gene in early zebrafish and mouse embryos results in ectopic appearance of
      endothelial cells. Ectopic expression of ETV2 in later development results in
      only a subset of cells responding to the signal. FINDINGS: We have examined the
      expression pattern of ETV2 in differentiating human embryonic stem cells (ESCs)
      to determine when the peak of ETV2 expression occurs. We show that overexpression
      of ETV2 in differentiating human ESC is able to increase the number of
      endothelial cells generated when administered during or after the endogenous peak
      of gene expression. CONCLUSIONS: Addition of exogenous ETV2 to human ESCs
      significantly increased the number of cells expressing angioblast genes without
      arterial or venous specification. This may be a viable solution to generate in
      vitro endothelial cells for use in research and in the clinic.

PMID- 25780561
TI  - Educational inequalities in young-adult mortality between the 1990s and the
      2000s: regional differences in Belgium.
AB  - BACKGROUND: This study addresses educational inequalities in young-adult
      mortality between the 1990s and the 2000s by comparing trends in the three
      different regions in Belgium stratified by sex. Social inequalities in mortality
      are of major concern to public health but are rarely studied at young ages.
      Substantial health differences have been found between the Flemish (FR) and
      Walloon region (WR) concerning (healthy) life expectancy and avoidable mortality,
      but little is known about regional differentials in young-adult mortality, and
      comparisons with the Brussels-Capital Region (BCR) have thus far never been made.
      METHODS: Data are derived from record linkage between the Belgian censuses of
      1991 and 2001 and register data on death and emigration for the periods
      01/03/1991-01/03/1999 and 01/10/2001-01/10/2009. Analyses are restricted to young
      adults aged 25 to 34 years at the moment of each of the censuses. Absolute
      (directly standardized mortality rates (ASMRs)) and relative (mortality rate
      ratio using Poisson regression) measures were calculated. RESULTS: There is a
      significant drop in young-adult mortality between the 1990s and the 2000s in all
      regions and both sexes, with the strongest decline in the BCR (e.g. ASMR of men
      declined from 165.6 [151.1-180.1] per 100,000 person years to 73.8 [88.3-98.3]).
      The mortality rates remain highest in the WR in the 2000s Between the 1990s and
      the 2000s, a remarkable change in the educational distribution occurred as well,
      with much lower proportions of primary educated in all regions in the 2000s in
      favour of higher proportions in all other educational levels, especially in
      higher education. All educational groups show lower mortality over time, except
      for lower educated men in the FR. CONCLUSIONS: There is a positive evolution
      towards lower mortality among the young-adult Belgian population. The WR trails
      behind in this evolution, which calls for tailored preventive actions.
      Educational inequalities are marked in all regions and time periods. A more
      general discussion is needed on the responsibility of society in rendering
      support and capability to enhance the state of well-being of those not able to
      achieve a high social position.

PMID- 25780562
TI  - The nutrition transition in Colombia over a decade: a novel household
      classification system of anthropometric measures.
AB  - BACKGROUND: Overweight and underweight increase the risk of metabolic impairments
      and chronic disease. Interventions at the household level require the diagnosis
      of nutritional status among family members. The aim of this study was to describe
      the prevalence and patterns of various anthropometric typologies over a decade in
      Colombia using a novel approach that considers all children in the household as
      well as the mother. This approach also allows identifying a dual burden of
      malnutrition within a household, where one child may be overweight and another
      one undernourished. METHODS: This study used data from the Demographic and Health
      Survey and the Colombian National Nutrition Survey [2000 n = 2,876, 2005 n =
      8,598, and 2010 n = 11,349]. Four mutually exclusive household (HH)
      anthropometric typologies - normal, undernourished, overweight/obese, and dual
      burden - were created. Anthropometric information of height-for-age Z-scores
      (HAZ) and body-mass-index-for-age Z-scores (BMIz) in children under the age of 5
      y, and on body mass index (BMI) in mothers, 18-49 y was used. RESULTS: Prevalence
      of overweight/obese HHs increased between 2000 (38.2%) and 2010 (43.1%) (p <
      0.05), while undernourished and dual burden HHs significantly decreased between
      2005 (13.7% and 10.6%, respectively) and 2010 (3.5% and 5.1%, respectively) (p <
      0.05). A greater increase of overweight/obesity was observed for the lowest
      quintile of wealth index (WI), with an increase of almost 10% between 2000 and
      2010, compared to 2% and 4% for the fourth and highest WI, respectively. Although
      in 2010 there is still a higher prevalence of overweight/obesity HHs in urban
      areas (43.7%), the prevalence of overweight/obesity HHs in rural areas increased
      sharply between 2000 (34.3%) and 2010 (41.6%) (p < 0.05). CONCLUSION: The
      observed prevalence of dual burden households was not different from the expected
      prevalence. Results from this study indicate that although overweight/obesity
      continues to be more prevalent among high-income Colombian households, it is
      growing at a faster pace among the most economically disadvantaged.

PMID- 25780564
TI  - The declarative system in children with specific language impairment: a
      comparison of meaningful and meaningless auditory-visual paired associate
      learning.
AB  - BACKGROUND: It has been proposed that children with Specific Language Impairment
      (SLI) have a selective deficit in procedural learning, with relatively spared
      declarative learning. In previous studies we and others confirmed deficits in
      procedural learning of sequences, using both verbal and nonverbal materials. Here
      we studied the same children using a task that implicates the declarative system,
      auditory-visual paired associate learning. There were parallel tasks for verbal
      materials (vocabulary learning) and nonverbal materials (meaningless patterns and
      sounds). METHODS: Participants were 28 children with SLI aged 7-11 years, 28
      younger typically-developing children matched for raw scores on a test of
      receptive grammar, and 20 typically-developing children matched on chronological
      age. Children were given four sessions of paired-associate training using a
      computer game adopting an errorless learning procedure, during which they had to
      select a picture from an array of four to match a heard stimulus. In each session
      they did both vocabulary training, where the items were eight names and pictures
      of rare animals, and nonverbal training, where stimuli were eight visual patterns
      paired with complex nonverbal sounds. A total of 96 trials of each type was
      presented over four days. RESULTS: In all groups, accuracy improved across the
      four sessions for both types of material. For the vocabulary task, the age
      matched control group outperformed the other two groups in the starting level of
      performance, whereas for the nonverbal paired-associate task, there were no
      reliable differences between groups. In both tasks, rate of learning was
      comparable for all three groups. CONCLUSIONS: These results are consistent with
      the Procedural Deficit Hypothesis of SLI, in finding spared declarative learning
      on a nonverbal auditory-visual paired associate task. On the verbal version of
      the task, the SLI group had a deficit in learning relative to age-matched
      controls, which was evident on the first block in the first session. However, the
      subsequent rate of learning was consistent across all three groups. Problems in
      vocabulary learning in SLI could reflect the procedural demands of remembering
      novel phonological strings; declarative learning of crossmodal links between
      auditory and visual information appears to be intact.

PMID- 25780565
TI  - Andrologie becomes Basic and Clinical Andrology.

PMID- 25780566
TI  - Erectile function after permanent 125I prostate brachytherapy for localized
      prostate cancer.
AB  - BACKGROUND AND PURPOSE: To analyze erectile function in men treated by prostate
      brachytherapy (PB) for localized prostate cancer. MATERIAL AND METHODS: Of a
      series of 270 sexually active men treated by PB, 241 (89%), mean age 65 yr
      (range, 43-80 yr), participated in a study on erectile function that was
      evaluated using the International Index of Erectile Function 5-item (IIEF-5)
      questionnaire before implantation and by postal survey after a mean follow-up of
      36 months (range, 6-70 months). RESULTS: After PB, 27 patients (11%) had no
      erectile dysfunction (ED), 36 (15%) had mild ED, 58 (24%) had mild to moderate
      ED, 24 (10%) had moderate ED, 53 (22%) had severe ED and 43 (18%) were not
      sexually active. In patients with a preimplant IIEF score >12 (cut-off for
      intercourse with penetration), 73% had a deterioration of erectile function by at
      least one class after PB. Risk factors for ED after PB were age, preimplant IIEF
      score and prostate volume. Median time to ED onset was 16 months and was shorter
      with androgen deprivation (p = 0.007), diabetes (p = 0.03) and age over 55 (p =
      0.01). CONCLUSIONS: Following PB, the majority of patients progressively develop
      or major ED after a free interval that may last several months. SUPPORT: Ligue
      Nationale contre le Cancer, France.

PMID- 25780567
TI  - The nature of human sperm head vacuoles: a systematic literature review.
AB  - Motile sperm organelle morphology examination (MSOME) involves the use of
      differential interference contrast microscopy (also called Nomarski contrast) at
      high magnification (at least 6300x) to improve the observation of live human
      spermatozoa. In fact, this technique evidences sperm head vacuoles that are not
      necessarily seen at lower magnifications - particularly if the vacuoles are small
      (i.e. occupying <4% of the sperm head's area). However, a decade after MSOME's
      introduction, it is still not clear whether sperm head vacuoles are nuclear,
      acrosomal and/or membrane-related in nature. In an attempt to clarify this
      debate, we performed a systematic literature review in accordance with the PRISMA
      guidelines. The PubMed database was searched from 2001 onwards with the terms
      "MSOME", "human sperm vacuoles", "high-magnification, sperm". Out of 180 search
      results, 21 relevant English-language publications on the nature of human sperm
      head vacuoles were finally selected and reviewed. Our review of the literature
      prompted us to conclude that sperm-head vacuoles are nuclear in nature and are
      related to chromatin condensation failure and (in some cases) sperm DNA damage. 

PMID- 25780568
TI  - In Vitro fertilization failure of normozoospermic men: search for a lack of
      testicular isozyme of angiotensin-converting enzyme.
AB  - BACKGROUND: Angiotensin converting enzyme (ACE) is a metalloprotease with two
      isoforms. The somatic isoform is a key component of the renin-angiotensin system;
      its main function is to hydrolyse angiotensin I into angiotensin II. The germinal
      or testicular isoform (tACE) located at the plasma membrane of the spermatozoa,
      plays a crucial role in the spermatozoa-oocyte interaction during in vivo
      fertilization, in rodents. Disruption of the tACE in mice has revealed that
      homozygous male tACE-/- sire few pups despite mating normally. Few spermatozoa
      from these tACE-/- mice are bound to the zona pellucida (ZP) despite normal semen
      parameters. Based on these findings in mice models, we hypothesized that some
      infertile men that have the same phenotype as the tACE-/- mice, ie normal semen
      parameters and a lack of sperm bind to the ZP in vitro, may have a tACE defect.
      METHODS: Twenty four men participated to this study. The case subjects (n = 10)
      had normal semen parameters according to the WHO guidelines (WHO 1999) but a
      total in vitro fertilization failure with absence of sperm fixation to the ZP.
      The control subjects (n = 14) also had normal semen parameters and a normal
      fertilization rate >=65%. We investigated the tACE expression in spermatozoa by
      Western-Blot and performed a DNA sequencing of the tACE gene. RESULTS: Three case
      subjects and one control-subject had no tACE expression. There were no statistic
      differences between the two groups. No mutation was detected in the tACE DNA
      sequence. CONCLUSIONS: Our results didn't show any involvement of tACE in human
      fertilization especially in ZP binding.

PMID- 25780569
TI  - Comparative testicular transcriptome of wild type and globozoospermic Dpy19l2
      knock out mice.
AB  - BACKGROUND: Globozoospermia is a male infertility phenotype characterized by the
      presence in the ejaculate of near 100% acrosomeless round-headed spermatozoa with
      normal chromosomal content. Following intracytoplasmic sperm injection (ICSI)
      these spermatozoa give a poor fertilization rate and embryonic development. We
      showed previously that most patients have a 200 kb homozygous deletion, which
      includes DPY19L2 whole coding sequence. Furthermore we showed that the DPY19L2
      protein is located in the inner nuclear membrane of spermatids during
      spermiogenesis and that it is necessary to anchor the acrosome to the nucleus
      thus performing a function similar to that realized by Sun proteins within the
      LINC-complex (Linker of Nucleoskeleton and Cytoskeleton). SUN1 was described to
      be necessary for gametogenesis and was shown to interact with the telomeres. It
      is therefore possible that Dpy19l2 could also interact, directly or indirectly,
      with the DNA and modulate gene expression during spermatogenesis. In this study,
      we compared the transcriptome of testes from Dpy19l2 knock out and wild type mice
      in order to identify a potential deregulation of transcripts that could explain
      the poor fertilization potential of Dpy19l2 mutated spermatozoa. METHODS: RNA was
      extracted from testes from DPY19L2 knock out and wild type mice. The
      transcriptome was carried out using GeneChip(r) Mouse Exon 1.0 ST Arrays. The
      biological processes and molecular functions of the differentially regulated
      genes were analyzed with the PANTHER software. RESULTS: A total of 76 genes were
      deregulated, 70 were up-regulated and 6 (including Dpy19l2) were down-regulated.
      These genes were found to be involved in DNA/RNA binding, structural
      organization, transport and catalytic activity. CONCLUSIONS: We describe that an
      important number of genes are differentially expressed in Dpy19l2 mice. This work
      could help improving our understanding of Dpy19l2 functions and lead to a better
      comprehension of the molecular mechanism involved in spermatogenesis.

PMID- 25780570
TI  - The immunobiology of the mammalian epididymis: the black box is now open!
AB  - Spermatozoa represent an immunologic challenge for the mammalian males. They are
      produced long after the establishment of the immune library of the individual and
      harbor specific spermatic antigens that are found nowhere else in other organs,
      tissues and cells. Consequently, spermatozoa are somehow "foreign" to the male
      adaptive immune system. In order not to elicit autoimmune responses that would be
      detrimental for male fertility, spermatozoa should be either physically separated
      from the adaptive immune response and/or, the immune system challenged by
      spermatic antigens must be efficiently silenced. Within the mammalian male
      genital tract it becomes more and more obvious that a range of strategies are at
      stake to ensure that the immune-stranger spermatozoa do not constitute an
      immunological issue. In this review the focus will be on the immune status of the
      epididymis tubule, in which spermatozoa that have left the testes will mature for
      approximately 2 weeks and may be stored for prolonged period of time. How the
      epididymal immune environment compares to that of the testis and what are the
      immune regulatory processes at work in the epididymal compartment will only be
      briefly described. Instead, this review will focus on recent data that highlight
      epididymal immune regulatory actors that partly explain/illustrate the rather
      complicated, fragile but nevertheless robust immune environment of the
      epididymis. 

PMID- 25780571
TI  - RNA: a possible contributor to the 'missing heritability'.
AB  - A number of human pathologies have a transmission pattern that does not obey
      Mendelian segregation rules. This type of heredity is defined as non-Mendelian
      and is based on mechanisms of transgenerational epigenetic inheritance.
      Comprehensive information on the molecular mechanisms of it is still lacking.
      However, recent evidence from distantly related species including Caenorhabditis
      elegans, Drosophila, and mouse, points towards a role for non-coding RNA
      molecules in such a pattern of inheritance. While it would be too hasty to
      conclude that RNA molecules are at work in the transgenerational non-genetic
      inheritance of human pathologies, a growing number of studies seem to strongly
      support such a speculation. 

PMID- 25780572
TI  - Intracytoplasmic morphologically selected sperm injection (IMSI): a critical and
      evidence-based review.
AB  - Introduced in 2001, intracytoplasmic morphologically selected sperm injection
      (IMSI) represents a more sophisticated way of ICSI whereby, prior to injection,
      the spermatozoon is selected at higher magnification. Doing so, the spermatozoon
      can be evaluated for fine integrity of its nucleus and the injection of a normal
      spermatozoon with a vacuole-free head can be assured. Additional research is
      needed to unravel the underlying mechanisms responsible for the presence of
      vacuoles in sperm heads. Associations with acrosome status, chromatin
      condensation, DNA fragmentation and sperm aneuploidy have been documented,
      however, controversy on their nature exists. Spermatozoon shape and large
      vacuoles are detected and deselected in conventional ICSI as well. However, the
      detection of subtle small vacuoles depends on the resolving power of the optical
      system and may impact oocyte fertilization, embryo development and implantation.
      Several comparative studies have indicated that the use of high-magnification
      sperm selection was associated with both higher pregnancy and delivery rates,
      whereas also lower miscarriage rates were observed. However, still to date
      randomized, well-powered studies to confirm these findings are scarce and show
      conflicting results. Hence, the most relevant indications for IMSI still remain
      to be determined. Two groups of patients have been put forward i.e. severe male
      factor infertility patients and patients with a history of repeated ICSI
      failures. However, for both groups limited to no proof of any benefit does exist.
      IMSI is a time-consuming procedure at the expense of oocyte ageing. The lack of
      proof and understanding of its benefit does not justify its routine clinical
      application at present. 

PMID- 25780573
TI  - "Breaking news" from spermatids.
AB  - During the haploid phase of spermatogenesis, spermatids undergo a complex
      remodeling of the paternal genome involving the finely orchestrated replacement
      of histones by the highly-basic protamines. The associated striking change in DNA
      topology is characterized by a transient surge of both single- and double
      stranded DNA breaks in the whole population of spermatids which are repaired
      before spermiation. These transient DNA breaks are now considered part of the
      normal differentiation program of these cells. Despite an increasing interest in
      the study of spermiogenesis in the last decade and the potential threat to the
      haploid genome, the origin of these DNA breaks still remains elusive. This review
      briefly outlines the current hypotheses regarding possible mechanisms that may
      lead to such transient DNA fragmentation including torsional stress, enzyme
      induced breaks, apoptosis-like processes or oxidative stress. A better
      understanding of the origin of these DNA breaks will lead to further
      investigations on the genetic instability and mutagenic potential induced by the
      chromatin remodeling. 

PMID- 25780574
TI  - Expression and localization of aromatase during fetal mouse testis development.
AB  - BACKGROUND: Both androgens and estrogens are necessary to ensure proper testis
      development and function. Studies on endocrine disruptors have highlighted the
      importance of maintaining the balance between androgens and estrogens during
      fetal development, when testis is highly sensitive to environmental disturbances.
      This balance is regulated mainly through an enzymatic cascade that converts
      irreversibly androgens into estrogens. The most important and regulated component
      of this cascade is its terminal enzyme: the cytochrome p450 19A1 (aromatase
      hereafter). This study was conducted to improve our knowledge about its
      expression during mouse testis development. FINDINGS: By RT-PCR and western
      blotting, we show that full-length aromatase is expressed as early as 12.5 day
      post-coitum (dpc) with maximal expression at 17.5 dpc. Two additional truncated
      transcripts were also detected by RT-PCR. Immunostaining of fetal testis sections
      and of gonocyte-enriched cell cultures revealed that aromatase is strongly
      expressed in fetal Leydig cells and at variable levels in gonocytes. Conversely,
      it was not detected in Sertoli cells. CONCLUSIONS: This study shows for the first
      time that i) aromatase is expressed from the early stages of fetal testis
      development, ii) it is expressed in mouse gonocytes suggesting that fetal germ
      cells exert an endocrine function in this species and that the ratio between
      estrogens and androgens may be higher inside gonocytes than in the interstitial
      fluid. Furthermore, we emphasized a species-specific cell localization. Indeed,
      previous works found that in the rat aromatase is expressed both in Sertoli and
      Leydig cells. We propose to take into account this species difference as a new
      concept to better understand the changes in susceptibility to Endocrine
      Disruptors from one species to another.

PMID- 25780575
TI  - FISH and tips: a large scale analysis of automated versus manual scoring for
      sperm aneuploidy detection.
AB  - BACKGROUND: Approximately 1% of the spermatozoa found in ejaculate of healthy men
      are aneuploid and this rate increases in the population of subfertile and
      infertile men. Moreover, fertilization with these aneuploid sperm can lead to
      impaired embryo development. Fluorescent In Situ Hybridization (FISH) is the
      common cytogenetic tool used for aneuploidy screening on sperm. However, it is a
      time-consuming technique and cytogenetic or in vitro fertilization laboratories
      cannot routinely use it and face the increasing demand of such analyses before
      Assisted Reproductive Techniques (ART). As automation can be a clue for routine
      practice, this study compares manual and automated scoring of sperm aneuploidy
      rates using a Metafer Metasystems(r) device. The results obtained also contribute
      to global data about FISH on sperm cells. METHODS: We recruited 100 men addressed
      for sperm cryopreservation. They all signed an informed consent to participate in
      the study. 29 men were donors or consulted before vasectomy (control group) and
      71 were suffering of Hodgkin's disease or non Hodgkin lymphoma (patient group).
      One semen sample was collected for each patient, analyzed according to WHO
      criteria and prepared for a triple-color FISH using centromeric probes for
      chromosomes 18, X and Y. Automated scoring was performed using a Metafer
      Metasystems(r) device. RESULTS: 507,019 cells were scored. We found a strong
      concordance between the automated and the manual reading (d < 0.01 in Bland
      Altman test). We also did not find a statistically significant difference between
      the automated and the manual reading using Wilcoxon test for total aneuploidy
      rate (p = 0.06), sex chromosomes disomy (p = 0.33), chromosome 18 disomy (p =
      0.39) and diploidy (p = 0.21). Cumulative rate of total aneuploidy was 0.78% +/-
      0.212% for patient group and 0.54% +/- 0.15 for control group and among this, sex
      chromosome XY disomy rate was of 0.54% for patient group and 0.27% for control
      group. CONCLUSION: This study validates the automated reading for FISH on sperm
      with a Metafer Metasystems(r) device and allows its use in a laboratory routine.

PMID- 25780576
TI  - Outcomes with intracytoplasmic sperm injection of cryopreserved sperm from men
      with spinal cord injury.
AB  - BACKGROUND: Erectile dysfunction, ejaculatory dysfunction and poor semen quality
      are the main causes of infertility in men with spinal cord injury (SCI).
      Different sperm retrieval techniques such as penile vibratory stimulation (PVS),
      electro-ejaculation (EEJ) or surgical sperm retrieval (SSR) associated or not
      with sperm cryopreservation can be offered to these patients to preserve their
      fertility. If fatherhood cannot be achieved naturally, assisted reproductive
      techniques can be offered to these patients using either fresh or frozen/thawed
      sperm. The aim of the study was to report in SCI patients from Dijon (Burgundy)
      and in the literature, intracytoplasmic sperm injection (ICSI) outcomes using
      frozen sperm obtained either by antegrade ejaculation (PVS or sexual intercourse)
      or by SSR. METHODS: A retrospective analysis was performed in Dijon, Burgundy
      over a 17 year period (1995-2011) on a cohort of 19 SCI men (6 quadriplegics and
      13 paraplegics, mean age: 25.2 +/- 5.6 years) who underwent a sperm
      cryopreservation followed or not by intracytoplasmic sperm injection (ICSI).
      Patients were divided into two groups according to the sperm retrieval method
      used (antegrade ejaculation group (n=10): penile vibratory stimulation (PVS) for
      9 patients and sexual intercourse for 1 patient and surgical sperm retrieval
      (SSR) group: n=9). The sperm parameters in both groups were analyzed. Pregnancy
      outcomes in the 8 couples who underwent ICSI were evaluated. RESULTS: The
      fertilization rates were 57 and 55%, the embryo's cleavage rates were 90 and 93%
      in the antegrade ejaculation and SSR groups respectively. Among the 8 couples who
      underwent ICSI, 5 couples achieved pregnancy. The pregnancy rates per couple were
      50% and 75% in the antegrade and SSR groups respectively. CONCLUSIONS: Although
      some studies don't recommend freezing sperm in SCI patients, the pregnancy rates
      presented in this study are encouraging and warrant the use of frozen/thawed
      sperm in very specific situations.

PMID- 25780577
TI  - Identity suffering in infertile men.
AB  - The suffering caused by infertility in a man can have multiple aspects. It can
      display a narcissistic dimension, an objectal dimension (object-libido) turned
      toward others or/and an identity dimension. Two clinical case reports were used
      here to (i) illustrate all these aspects of infertility suffering, (ii) to
      evidence the difficulty for infertile men to speak about their infertility and
      (iii) underlie the importance for professional of medical assisted reproduction
      to be attentive to this suffering that many men keep silent. An empathetic
      attention to infertile men may give a way to express this suffering and thus
      allow the beginning of a psychoanalytic approach which is necessary in
      infertility and especially for infertile men who do not easily express their
      suffering. 

PMID- 25780578
TI  - RHOXF2 gene, a new candidate gene for spermatogenesis failure.
AB  - INTRODUCTION: Genes involved in testicular differentiation, spermatogenesis,
      proliferation and apoptosis of germ cells have been shown to evolve rapidly and
      display rapid DNA changes. These genes are therefore good candidates for
      explaining impairments in spermatogenesis. Initial studies of some of these genes
      appear to confirm this hypothesis. The RHOXF2 candidate gene belongs to the RHOX
      family clustered in Xq24 and is specifically expressed in the testis. It contains
      four exons and codes for a 288 amino acid (aa) transcription factor. It has a
      high degree of homology (>99.9%) with its paralogue RHOXF2B, which is also
      preferentially expressed in the testis. OBJECTIVES: To sequence RHOXF2 and
      RHOXF2B in intracytoplasmic sperm injection (ICSI) patients and identify any
      single-nucleotide polymorphisms (SNPs) associated with impaired spermatogenesis.
      MATERIALS: A cohort of 327 patients in ICSI programmes at Poissy and Bichat
      hospitals. All patients gave their written, informed consent to participation.
      One hundred patients had unaffected spermatogenesis and 227 displayed impaired
      spermatogenesis. METHODS: The four exons in each of RHOXF2 and RHOXF2B were
      sequenced in 47 patients with oligospermia or non-obstructive azoospermia. Given
      that exons 2 and 3 were found to harbour most of the SNPs, only these two exons
      were sequenced in the remaining 280 subjects. RESULTS: Due to the extremely high
      degree of sequence identity between RHOXF2 and RHOXF2B, we were not able to
      distinguish between the sequences of these two genes. Although 9 SNPs were
      identified, there were no significant frequency differences between ICSI patients
      with normal vs. impaired spermatogenesis. Two insertions were identified: a 21
      nucleotide insertion was retrieved in both groups and a guanine insertion
      (inducing a premature stop codon) only found in two patients with impaired
      spermatogenesis. CONCLUSION/OUTLOOK: RHOXF2 is a good candidate for rapid
      evolution by positive selection. Analysis of the polymorphism frequency in exons
      2 and 3 did not allow us to correlate the identified SNPs with male infertility.
      However, a single nucleotide insertion was identified only in men with impaired
      spermatogenesis. Further work will be needed to establish whether genetic changes
      in RHOXF2 can give rise to defects in spermatogenesis.

PMID- 25780580
TI  - Penile Mondor's disease.
AB  - Mondor's disease is a rare, self-limiting, benign process with acute presentation
      characterized by subcutaneous bands in several parts of the body. Penile Mondor's
      disease (PMD) is thrombophlebitis of the superficial dorsal vein of the penis. It
      is usually considered as thrombophlebitis or phlebitis of subcutaneous vessels.
      Some findings suggest that it might be of lymphatic origin. The chest, abdominal
      wall, penis, upper arm, and other parts of the body may also be involved by the
      disease. Although its physiopathology is not exactly known, transection of the
      vessel during surgery or any type of trauma such as external compression may
      trigger its possible development. This disease almost always limits itself. It
      may be associated with psychological distress and sexual incompatibility. The
      patients usually feel the superficial vein of the penis like a hard rope and
      present with complaint of pain around this hardness. Diagnosis is usually easy
      with physical examination but color Doppler ultrasound examination is important
      for differential diagnosis. Thus, a close collaboration is required between
      radiologist and urologist in order to determine the correct diagnosis and
      appropriate therapies. 

PMID- 25780579
TI  - Peroxiredoxins: hidden players in the antioxidant defence of human spermatozoa.
AB  - Spermatozoon is a cell with a precious message to deliver: the paternal DNA. Its
      motility machinery must be working perfectly and it should be able to acquire
      fertilizing ability in order to accomplish this mission. Infertility touches 1 in
      6 couples worldwide and in half of the cases the causes can be traced to men. A
      variety of conditions such as infections of the male genital tract, varicocele,
      drugs, environmental factors, diseases, smoking, etc., are associated with male
      infertility and a common feature among them is the oxidative stress in semen that
      occurs when reactive oxygen species (ROS) are produced at high levels and/or when
      the antioxidant systems are decreased in the seminal plasma and/or spermatozoa.
      ROS-dependent damage targets proteins, lipids, and DNA, thus compromising sperm
      function and survival. Elevated ROS in spermatozoa are associated with DNA damage
      and decreased motility. Paradoxically, ROS, at very low levels, regulate sperm
      activation for fertilization. Therefore, the regulation of redox signaling in the
      male reproductive tract is essential for fertility. Peroxiredoxins (PRDXs) play a
      central role in redox signaling being both antioxidant enzymes and modulators of
      ROS action and are essential for pathological and physiological events. Recent
      studies from our lab emphasize the importance of PRDXs in the protection of
      spermatozoa as infertile men have significant low levels of PRDXs in semen and
      with little enzymatic activity available for ROS scavenging. The relationships
      between sperm DNA damage, motility and lipid peroxidation and high levels of
      thiol-oxidized PRDXs suggest the enhanced susceptibility of spermatozoa to
      oxidative stress and further support the importance of PRDXs in human sperm
      physiology. This review aims to characterize PRDXs, hidden players of the sperm
      antioxidant system and highlight the central role of PRDXs isoforms in the
      protection against oxidative stress to assure a proper function and DNA integrity
      of human spermatozoa. 

PMID- 25780581
TI  - Eponyms in andrology.
AB  - Andrology is the study of male reproductive health, its associated medicines, and
      biology, including functions and diseases that are specific to men, especially
      with regard to the reproductive organs. This concise report discusses the eponyms
      that are encountered in andrological literature. 

PMID- 25780582
TI  - Precocious initiation of spermatogenesis in a 19-month-old boy with Hurler
      syndrome.
AB  - Mucopolysaccharidosis type IH (MPS IH) is a rare autosomal recessive lysosomal
      storage disorder. Haematopoietic stem cell transplantation (HSCT) has been
      proposed for the treatment of MPS IH patients and offers the possibility to grow
      into their adulthood. Precocious puberty has been described in few MPS patients.
      We report, to the best of our knowledge and for the first time, the initiation of
      the first waves of spermatogenesis fortuitously observed in seminiferous tubules
      of a pre-pubertal 19-month-old boy, affected by MPS IH and who did not present
      any clinical signs of precocious puberty. This patient benefited from testicular
      tissue cryopreservation before HSCT. Seminiferous tubule size, germ cell
      differentiation and Sertoli cell expression of androgen receptor and anti
      mullerian hormone corresponded to the pattern observed in a pubertal boy. The
      Hurler syndrome may be responsible for the precocious initiation of
      spermatogenesis. A specific follow-up during childhood may be useful to confirm
      if such abnormal testis development is common in young boys with MPS IH and if it
      may lead to precocious onset of puberty in survivors despite HSCT. Furthermore,
      we have observed that Sertoli cell maturation (up-regulation of AR expression,
      down-regulation of AMH expression) occurred before the clinical signs of puberty
      and before the increase of testosterone plasmatic level. 

PMID- 25780583
TI  - Beneficial effects of varicocele embolization on semen parameters.
AB  - BACKGROUND: The value of varicocele repair and the latter's impact on semen
      parameters are still subject to debate. METHODS: We analyse changes over time in
      initially abnormal sperm parameters and serum concentrations of testosterone, FSH
      and inhibin B after embolization treatment of males with high-grade varicocele.
      From 2007 to 2012, we recruited 47 male infertile patients with clinically
      visible left varicocele in the resting patient and at least one abnormal semen
      parameter. Sperm parameters and serum levels of total testosterone, FSH and
      inhibin B were measured prior to retrograde embolization (M0) and then 3 (M3) and
      6 (M6) months afterwards. RESULTS: At M0, the median sperm concentration was 5.78
      [0.84-37.70] * 10(6)/ejaculate. The mean +/- SD sperm progressive motility,
      vitality and percentage of normal sperm were respectively, 21.83 +/- 16.48%,
      61.88 +/- 15.98% and 12.88 +/- 7.15%. The corresponding values at M3 were
      significantly higher (38.75 [3.96-95] * 10(6)/ejaculate, 29.32 +/- 14.21%, 69.14
      +/- 14.86% and 19.03 +/- 11.02%, respectively). The mean percentage of
      spermatozoa with a thin head was significantly lower at M6 (6.35 +/- 5.29%) than
      at M0 (14.03 +/- 13.09%). The mean serum testosterone, FSH and inhibin B levels
      did not change significantly over time. CONCLUSIONS: Embolization treatment in
      men with clinically visible left varicocele, abnormal sperm parameters and
      documented infertility is associated with a significant improvement in semen
      parameters including sperm head morphology.

PMID- 25780584
TI  - A prospective study in male recipients of kidney transplantation reveals
      divergent patterns for inhibin B and testosterone secretions.
AB  - BACKGROUND: Male patients with chronic kidney disease often exhibit the
      biological and clinical hallmarks of an abnormal hypothalamo-pituitary-gonadal
      axis. It is known that dialysis does not reverse this impaired endocrine status;
      however, the impact of kidney transplantation (KT) is still controversial. The
      aim of our study was to investigate the levels of serum gonadotropins,
      testosterone, and inhibin B during dialysis and after KT. METHODS: A longitudinal
      and prospective single center study was led in an academic setting. Blood
      hormones levels were assayed by immunoassays in 53 men (mean age: 37 years)
      receiving dialysis (T0) and at 6 months post-KT (T180). These data were compared
      with those from 46 fertile semen donors (mean age: 37 years). The main outcome
      measure was the between-groups differences in hormones levels. A second criterion
      was the comparison of T0 and T180 hormones levels according to the
      immunosuppressive regimen. RESULTS: For patients ongoing dialysis, luteinizing
      hormone (LH) and follicle-stimulating hormone (FSH) mean levels were high,
      whereas testosterone and inhibin B mean levels remained normal. After KT, LH
      levels returned to normal whereas FSH was significantly increased. Testosterone
      levels remained normal whereas inhibin B levels significantly decreased. We found
      that the combination tacrolimus plus mycophenolic acid significantly decreased
      post-KT inhibin B levels. Moreover, we found that pre-graft inhibin-B level was
      independent of testosterone and could predict low post-operative inhibin B level
      with a sensitivity of 77% and a specificity of 92%. CONCLUSIONS: Our study
      suggests that endocrine secretions of Leydig and Sertoli cells are differently
      impacted by dialysis, KT and immunosuppressive regimen raising new issues to
      explore.

PMID- 25780585
TI  - The emerging role of insulin-like growth factors in testis development and
      function.
AB  - The insulin-like family of growth factors (IGFs) - composed of insulin, and
      insulin-like growth factors I (IGF1) and II (IGF2) - provides essential signals
      for the control of testis development and function. In the testis, IGFs act in an
      autocrine-paracrine manner but the extent of their actions has been
      underestimated due to redundancies at both the ligand and receptor levels, and
      the perinatal lethality of constitutive knockout mice. This review synthesizes
      the current understanding of how the IGF system regulates biological processes
      such as primary sex determination, testis development, spermatogenesis and
      steroidogenesis, and highlights the questions that remain to be explored. 

PMID- 25780586
TI  - Evaluation of sexual functions and sexual behaviors after penile brachytherapy in
      men treated for penile carcinoma.
AB  - PURPOSE: To assess sexual functions and behaviors of men treated by penile
      brachytherapy for a cancer of the penis. MATERIALS AND METHODS: Thirty eight men
      (19 patients treated by penile brachytherapy for a cancer of the penis and 19 age
      paired-matched controls) participated in a survey about sexuality. The mean age
      of patients and controls were 73.2 +/- 11.7 and 70.0 +/- 10.5 years, respectively
      (NS). Controls were men without penile pathology, without history of cancer and
      no evidence of cognitive impairment. All agreed to participate in the survey
      about sexuality using 2 questionnaires : the IIEF questionnaire, which explores 4
      domains of sexual functions, namely erection, satisfaction, orgasm and desire,
      and a questionnaire created using the BASIC IDEA grid, which addresses nine
      domains: behavior, affect, sensation, self-image, cognition, interpersonal,
      drugs, expectation and attitude. RESULTS: Patients had better scores than
      controls in 3 domains of the IIEF: erection, desire and satisfaction. These
      results contrasted with the frequency of intercourse and the quality of erection
      (evaluated through the BASIC IDEA questionnaire) that were not significantly
      different between the two populations. Patients also had significantly higher
      frequency of masturbation (p <0.001) lower worry about sexual performance and
      higher expected satisfaction for future life (p: 0.021) than controls.
      CONCLUSION: Penile brachytherapy is a treatment of cancer of the penis that seems
      to have a moderated impact on sexual functions since most of sexual scores are
      not inferior in these patients than in age pair-matched controls.

PMID- 25780588
TI  - In cryptozoospermia or severe oligozoospermia is sperm freezing useful?
AB  - BACKGROUND: Intracytoplasmic Sperm Injection (ICSI) is an Assisted Reproduction
      Technique (ART) which offers the chance to conceive to patients presenting very
      low sperm counts (cryptozoospermia/severe oligozoospermia). Sperm freezing before
      the oocyte pick-up, can prevent from a lack of spermatozoa on the day of the
      ICSI. It can avoid the cancellation of the ICSI or the use of TESE (Testicular
      sperm extraction). The objective of this study was to analyse the practice of
      sperm freezing for these patients in our center over 8 years and the rate of use
      of these frozen sperms. We also compared the outcome of ICSIs with frozen versus
      ejaculated sperm. MATERIAL AND METHODS: We performed a retrospective
      epidemiological study between 2004 and 2011. We recruited all the patients having
      a sperm count below 1 Million/mL and who were waiting for their first ICSI
      attempt. RESULTS: 169 patients were recruited: 84 cryopreserved their sperm
      before the ICSI (secured ICSI) while 85 did not (non-secured ICSI). Both groups
      were split in cryptozoospermia (<10(3) spermatozoa/ml): 19 and 17 patients
      respectively, very severe oligozoospermia (10(3)-10(5)/ml): 37 and 13 patients,
      and severe oligozoospermia (10(5)-10(6)/ml): 28 and 55 patients. The part of
      secured ICSI significantly increased from 29% during 2004-2007 to 74% during 2008
      2011(p = 0.0029) and the frozen sperm was used in 5.9% of the cases. Median age
      was significantly higher in the non secured ICSI group (33.57 vs 35.52 for men, p
      = 0.0069 and 30.45 vs 32.26 for women, p = 0.025) but no significant difference
      was found in the outcome of the ICSI between frozen-thawed sperm and fresh
      ejaculated sperm. CONCLUSION: Sperm freezing before ICSI for severe
      oligozoospermic and cryptozoospermic patients significantly increased in our
      practice but the rate of use remain very low. This encourages to define more
      accurate criteria leading to sperm freezing.

PMID- 25780589
TI  - Reconstructive surgery for giant penoscrotal elephantiasis: about one case.
AB  - Elephantiasis of the external genitalia is characterized by lymphedema and
      thickening of the subcutaneous tissues. This gives the skin an appearance similar
      to a pachyderm skin. This pathology is invalidating for the patient.
      Reconstructive surgery is often the only way to restaure aesthetic and functional
      aspects of the external genitalia. We aim to report a 52 year man with huge
      penoscrotal elephantiasis who underwent excision and penoscrotal reconstruction
      at the department of Urology, Yalgado Ouedraogo Teaching Hospital at Ouagadougou.

PMID- 25780587
TI  - Man is not a big rat: concerns with traditional human risk assessment of
      phthalates based on their anti-androgenic effects observed in the rat foetus.
AB  - Phthalates provide one of the most documented example evidencing how much we must
      be cautious when using the traditional paradigm based on extrapolation of
      experimental data from rodent studies for human health risk assessment of
      endocrine disruptors (EDs). Since foetal testis is known as one of the most
      sensitive targets of EDs, phthalate risk assessment is routinely based on the
      capacity of such compounds to decrease testosterone production by the testis or
      to impair masculinization in the rat during foetal life. In this paper, the well
      established inhibiting effects of phthalates of the foetal Leydig cells function
      in the rat are briefly reviewed. Then, data obtained in humans and other species
      are carefully analysed. Already in January 2009, using the organotypic culture
      system named Fetal Testis Assay (FeTA) that we developed, we reported that
      phthalates might not affect testosterone production in human foetal testes.
      Several recent experimental studies using xenografts confirm the absence of
      detectable anti-androgenic effect of phthalates in the human foetal testes.
      Epidemiological studies led to contradictory results. Altogether, these findings
      suggest that phthalates effects on foetal Leydig cells are largely species
      specific. Consequently, the phthalate threshold doses that disturb foetal
      steroidogenesis in rat testes and that are presently used to define the
      acceptable daily intake levels for human health protection must be questioned.
      This does not mean that phthalates are safe because these compounds have many
      deleterious effects upon germ cell development that may be common to the
      different studied species including human. More generally, the identification of
      common molecular, cellular or/and phenotypic targets in rat and human testes
      should precede the choice of the toxicological endpoint in rat to accurately
      assess the safety threshold of any ED in humans. 

PMID- 25780590
TI  - Possible germ cell-Sertoli cell interactions are critical for establishing
      appropriate expression levels for the Sertoli cell-specific MicroRNA, miR-202-5p,
      in human testis.
AB  - BACKGROUND: To examine human microRNA expression in fertile men and subsequently
      to compare expression patterns of miRNAs in fertile and infertile men,
      specifically men with Sertoli Cell Only (SCO) histopathology. METHODS: Testicular
      tissues from men with azoospermia and SCO, as well as those of men with normal
      spermatogenesis, were analyzed. MicroRNA was isolated using the miRCURYTM RNA
      Purification Kit. A miRCURY LNATM Universal RT system was used for detection of
      microRNA by quantitative real-time PCR. MicroRNA localization was performed by in
      situ hybridizations (ISH) on formalin-fixed paraffin embedded (FFPE) tissue
      utilizing miRCURY LNATM microRNA ISH technology. Statistical analysis was
      performed by GenEx V5.0. RESULTS: MicroRNA expression was determined for 13
      normal fertile men and 5 men with the confirmed diagnosis of diffuse SCO. MiR-202
      5p expression was reduced by 17-fold (P < 0.00001) in tissue from SCO men
      compared to normal. MiR-34c-5p was reduced by 346-fold (P < 0.00001), miR-10b was
      reduced 18-fold (P < 0.00001), miR-191 was reduced 20-fold (P = 0.001) and miR
      126 was reduced 40-fold (P < 0.00001)) in tissues from SCO compared to normal
      fertile men. Using ISH, miR-202-5p was localized to Sertoli cells of men with
      normal spermatogenesis, but not in the Sertoli cells of men with SCO. CONCLUSION:
      Number of miRNAs are differentially expressed in normal fertile men compared to
      men with SCO. MicroRNA-202-5p is localized to Sertoli cells and its expression
      dramatically differs between fertile men and men whose germ cells are depleted,
      suggesting a novel interaction for regulating microRNA expression between the
      somatic and germ cell components of the seminiferous epithelium.

PMID- 25780591
TI  - Enhanced recovery programmes in colorectal surgery are less enhanced later in the
      week: An observational study.
AB  - OBJECTIVES: Since the introduction and favourable early results of the enhanced
      recovery programme more than a decade ago, it has become increasingly popular
      following major abdominal surgery. The programme has now been adopted in the UK.
      The aim of our study was to see if the day of surgery affected hospital stay and
      we compared patients who had colorectal surgery early in the week (Monday to
      Wednesday) with those who had it later in the week (Thursday to Friday). DESIGN:
      Patient outcomes were studied between May 2010 and April 2011 from a
      prospectively maintained database. All colorectal surgeons involved in the
      enhanced recovery programme in our unit have a flexible rota and so no surgeon
      was operating on a particular day to avoid bias. An enhanced recovery programme
      protocol was utilised for all the patients with no bowel preparation, early
      feeding and early mobilisation. SETTING: Study was carried out at the University
      Hospitals of Leicester. PARTICIPANTS: Patients undergoing elective colorectal
      resection between Monday and Friday. MAIN OUTCOME MEASURE: Hospital stay.
      RESULTS: Two hundred and twenty-seven patients underwent surgery and were on the
      enhanced recovery programme during this period. Two (0.9%) patients who had
      surgery on a Sunday were excluded. Two hundred and twenty-five patients were
      analysed of which 155 (69%) were in the group (Monday to Wednesday) and 70 (31%)
      in the group (Thursday to Friday). No significant differences were observed
      amongst the groups for age (p = 0.129), sex (p = 0.555), tumour location (p =
      0.140), operation performed (p = 0.127), type of surgery (laparoscopy or open, p
      = 0.892), complications (p = 0.428). However, a significant shorter length of
      stay was present in the first group six days (interquartile range: 4-10) versus
      eight days (interquartile range: 5-11) (p = 0.045). CONCLUSION: Operating on
      colorectal patients early in the week is associated with a significant decreased
      hospital stay. This should be put into consideration by units practising enhanced
      recovery programme if the maximal benefit of this is to be attained.

PMID- 25780592
TI  - A "Google Image" diagnosis of Madelung's disease.
AB  - Given the rare nature of Madelung's disease many clinicians will not have seen a
      patient with it and will not be able to recognise them: subsequently a diagnosis
      is unlikely to be made. 

PMID- 25780593
TI  - New onset diabetes after transplantation: Not another acronym!
AB  - New onset diabetes after transplantation is the onset of diabetes in previously
      non-diabetic individuals extending beyond the first month post-transplantation. 

PMID- 25780594
TI  - Adolescents' perception of substance use and factors influencing its use: a
      qualitative study in Abu Dhabi.
AB  - OBJECTIVE: The objective of this article is to gain a deeper understanding of the
      attitudes and perceptions of adolescents in the United Arab Emirates regarding
      substance and to identify factors that, in their view, may influence the risk of
      substance use and suggest possible interventions. DESIGN: This was a qualitative
      study that used a focus group approach. SETTING: The study was carried out in Abu
      Dhabi, United Arab Emirates. PARTICIPANTS: Male and female teenagers aged 13-18
      years residing in the emirate of Abu Dhabi. MAIN OUTCOME MEASURES: Adolescents'
      awareness of substance use, patterns of use and associated harm; Adolescents'
      perceptions about the factors associated with substance use. RESULTS: Six focus
      groups were carried out, and a total of 41 adolescents (20 males and 21 females)
      participated. Data analysis identified three main themes: (1) adolescents'
      awareness of substance use and associated harm; (2) gender role and image and (3)
      perceived factors affecting substance use among adolescents. Knowledge of
      substances and related consequences of use varied between groups but was
      compatible with participants' age and school years. Factors that participants
      believed influenced substance use were classified into: (1) parent-adolescent
      relationship, (2) peer pressure, (3) substance accessibility, (4) religiosity and
      (5) others. Many factors were believed to increase the risk of substance use
      among adolescents such as peer pressure, inadequate knowledge of the harmful
      consequences of drug use, family-related factors (e.g. low monitoring and poor
      parent-adolescents relationship), affordability and availability of substances,
      boredom and affluence. On the other hand, religiosity was as a shield against
      substance use, especially alcohol. Other identified protective factors included
      carrying out schools- and communities-based educational campaigns, enhancing
      social workers' ability to raise awareness and detect early signs of addiction
      and implementing CCTV systems in schools. CONCLUSIONS: The study was successful
      in exploring adolescents' awareness of substances and associated harm to health
      from their use. Also, it identifies a number of risk and protective factors based
      on the perceptions of a group of adolescents residing in the United Arab
      Emirates. Such factors can guide the planning, designing and implementing of
      prevention programmes that focus on raising awareness about the harms of
      substance use. The study findings would suggest that multifactorial prevention
      programmes that address social norms, gender role and image, and incorporate drug
      policy, religion, family and school would be more effective and may have better
      protective outcomes.

PMID- 25780595
TI  - Doctors currently in jobs with academic content and their future intentions to
      pursue clinical academic careers: questionnaire surveys.
AB  - OBJECTIVES: Our aim was to report on doctors' descriptions of their current post
      at about 12 years after qualification, in respect of academic content, and to
      compare this with their long-term intentions. By academic content, we mean posts
      that are designated as clinical academic posts or clinical service posts that
      include research and/or teaching commitments. DESIGN: Questionnaire survey.
      PARTICIPANTS: All UK medical graduates of 1996 contacted in 2007, graduates of
      1999 in 2012, and graduates of 2000 in 2012. SETTING: UK. MAIN OUTCOME MEASURES:
      Responses about current posts and future intentions. METHOD: Postal and email
      questionnaires. RESULTS: The response rate was 61.9% (6713/10844). Twenty eight
      per cent were working in posts with academic content (3.3% as clinical academics,
      25% in clinical posts with some academic content). Seventeen per cent of women
      were working in clinical posts with some teaching and research, compared with 29%
      of men. A higher percentage of men than women intended to be clinical academics
      as their eventual career choice (3.9% overall, 5.4% of men, 2.7% of women). More
      doctors wished to move to a job with an academic component than away from one (N
      = 824 compared with 236). This was true for both men (433 compared with 118) and
      women (391 compared with 118). CONCLUSIONS: Women are under-represented both in
      holding posts with academic content and in aspirations to do so. It is noteworthy
      that many more doctors hoped to move into an academic role than to move out of
      one. Policy should facilitate this wish in order to address current shortfalls in
      clinical academic medicine.

PMID- 25780596
TI  - Canadian Journal of Kidney Health and Disease: a unique launch of a unique
      journal.
AB  - Usually inaugural editorials are written by the Editor-in-Chief to describe the
      scope and vision for the journal to potential authors and readers. This editorial
      is written by the Editor-in-Chief, the Deputy Editors and the Associate Editors
      collaboratively as a clear signal that this is a unique and different journal. We
      will build this journal on a set of principles which are fundamental to improving
      the outcomes of patients with kidney disease. To that end, we aim to be
      supportive, to collaborate, to integrate multiple perspectives and to be open to
      possibilities. 

PMID- 25780597
TI  - Establishing a national knowledge translation and generation network in kidney
      disease: the CAnadian KidNey KNowledge TraNslation and GEneration NeTwork.
AB  - Patients with chronic kidney disease (CKD) do not always receive care consistent
      with guidelines, in part due to complexities in CKD management, lack of
      randomized trial data to inform care, and a failure to disseminate best practice.
      At a 2007 conference of key Canadian stakeholders in kidney disease, attendees
      noted that the impact of Canadian Society of Nephrology (CSN) guidelines was
      attenuated given limited formal linkages between the CSN Clinical Practice
      Guidelines Group, kidney researchers, decision makers and knowledge users, and
      that further knowledge was required to guide care in patients with kidney
      disease. The idea for the Canadian Kidney Knowledge Translation and Generation
      Network (CANN-NET) developed from this meeting. CANN-NET is a pan-Canadian
      network established in partnership with CSN, the Kidney Foundation of Canada and
      other professional societies to improve the care and outcomes of patients with
      and at risk for kidney disease. The initial priority areas for knowledge
      translation include improving optimal timing of dialysis initiation, and
      increasing the appropriate use of home dialysis. Given the urgent need for new
      knowledge, CANN-NET has also brought together a national group of experienced
      Canadian researchers to address knowledge gaps by encouraging and supporting
      multicentre randomized trials in priority areas, including management of
      cardiovascular disease in patients with kidney failure. 

PMID- 25780598
TI  - An assessment of dialysis provider's attitudes towards timing of dialysis
      initiation in Canada.
AB  - BACKGROUND: Physicians' perceptions and opinions may influence when to initiate
      dialysis. OBJECTIVE: To examine providers' perspectives and opinions regarding
      the timing of dialysis initiation. DESIGN: Online survey. SETTING: Community and
      academic dialysis practices in Canada. PARTICIPANTS: A nationally-representative
      sample of dialysis providers. MEASUREMENTS AND METHODS: Dialysis providers
      opinions assessing reasons to initiate dialysis at low or high eGFR. Responses
      were obtained using a 9-point Likert scale. Early dialysis was defined as
      initiation of dialysis in an individual with an eGFR greater than or equal to
      10.5 ml/min/m(2). A detailed survey was emailed to all members of the Canadian
      Society of Nephrology (CSN) in February 2013. The survey was designed and pre
      tested to evaluate duration and ease of administration. RESULTS: One hundred and
      forty one (25% response rate) physicians participated in the survey. The majority
      were from urban, academic centres and practiced in regionally administered renal
      programs. Very few respondents had a formal policy regarding the timing of
      dialysis initiation or formally reviewed new dialysis starts (N = 4, 3.1%). The
      majority of respondents were either neutral or disagreed that late compared to
      early dialysis initiation improved outcomes (85-88%), had a negative impact on
      quality of life (89%), worsened AVF or PD use (84-90%), led to sicker patients
      (83%) or was cost effective (61%). Fifty-seven percent of respondents felt uremic
      symptoms occurred earlier in patients with advancing age or co-morbid illness.
      Half (51.8%) of the respondents felt there was an absolute eGFR at which they
      would initiate dialysis in an asymptomatic patient. The majority of respondents
      would initiate dialysis for classic indications for dialysis, such as volume
      overload (90.1%) and cachexia (83.7%) however a significant number chose other
      factors that may lead them to early dialysis initiation including avoiding an
      emergency (28.4%), patient preference (21.3%) and non-compliance (8.5%).
      LIMITATIONS: 25% response rate. CONCLUSIONS: Although the majority of
      nephrologists in Canada who responded followed evidence-based practice regarding
      the timing of dialysis initiation, knowledge gaps and areas of clinical
      uncertainty exist. The implementation and evaluation of formal policies and
      knowledge translation activities may limit potentially unnecessary early dialysis
      initiation.

PMID- 25780599
TI  - Views of Canadian patients on or nearing dialysis and their caregivers: a
      thematic analysis.
AB  - BACKGROUND: Quality of life of patients receiving dialysis has been rated as
      poor. OBJECTIVE: To synthesize the views of Canadian patients on or nearing
      dialysis, and those who care for them. DESIGN: Secondary analysis of a survey,
      distributed through dialysis centres, social media and the Kidney Foundation of
      Canada. SETTING: Pan-Canadian convenience sample. PARTICIPANTS: Patients, their
      caregivers and health-care providers. MEASUREMENTS: Text responses to open-ended
      questions on topics relevant to end-stage renal disease. METHODS: Statements
      related to needs, beliefs or feelings were identified, and were analysed by
      thematic content analysis. RESULTS: A total of 544 relevant statements from 189
      respondents were included for the thematic content analysis. Four descriptive
      themes were identified through the content analysis: gaining knowledge,
      maintaining quality of life, sustaining psychosocial wellbeing and ensuring
      appropriate care. Respondents primarily identified a need for more information,
      better communication, increased psychosocial and financial support for patients
      and their families and a strong desire to maintain their previous lifestyle.
      LIMITATIONS: Convenience sample; questions were originally asked with a different
      intent (to identify patient-important research issues). CONCLUSIONS: Patients on
      or nearing dialysis and their caregivers identified four major themes, gaining
      knowledge, maintaining quality of life, sustaining psychosocial wellbeing and
      ensuring appropriate care, several of which could be addressed by the health care
      system without requiring significant resources. These include the development of
      patient materials and resources, or sharing of existing resources across Canadian
      renal programs, along with adopting better communication strategies. Other
      concerns, such as the need for increased psychosocial and financial support,
      require consideration by health care funders.

PMID- 25780600
TI  - The Canadian Society of Nephrology methods in developing and adapting clinical
      practice guidelines: a review.
AB  - INTRODUCTION: The Canadian Society of Nephrology (CSN) was established to promote
      the highest quality of care for patients with renal diseases and to encourage
      research related to the kidney and its disorders. The CSN Clinical Practice
      Guideline (CPG) Committee develops guidelines with clear recommendations to
      influence physicians' practice and improve the health of patients with kidney
      disease in Canada. REVIEW: In this review we describe the CSN process in
      prioritizing CPGs topics. We document the CSN experience using the Grading of
      Recommendations Assessment, Development and Evaluation (GRADE) approach. We then
      detail the CSN process in developing de novo CPGs and in adapting existing CPGs
      and developing accompanying commentaries. We also discuss challenges faced during
      this process and suggest solutions. Furthermore, we summarize the CSN effort in
      disseminating and implementing their guidelines. Additionally, we describe recent
      development and partnerships that allow evaluation of the effect of the CSN
      guidelines and commentaries. CONCLUSION: The CSN follows a comprehensive process
      in identifying priority areas to be addressed in CPGs. In 2010, the CSN adopted
      GRADE, which enhanced the rigor and transparency of guideline development. This
      process focuses on systematically identifying best available evidence and
      carefully assessing its quality, balancing benefits and harms, considering
      patients' and societies' values and preferences, and when possible considering
      resource implications. Recent partnership allows wider dissemination and
      implementation among end users and evaluation of the effects of CPG and
      commentaries on the health of Canadians.

PMID- 25780601
TI  - Foundations and principles of the Canadian living donor paired exchange program.
AB  - PURPOSE OF REVIEW: Kidney paired donation (KPD) remains an important strategy to
      facilitate transplantation in patients who have a healthy and willing donor, but
      are unable to proceed with directed donation due to either ABO incompatibility or
      a positive cross-match against their intended donor. SOURCES OF INFORMATION:
      Personal knowledge, The Canadian Blood Services Database for Living Donor
      Exchange, published reports and personal communications. FINDINGS: The national
      Living Donor Paired Exchange Programme (LDPE) in Canada was established in 2009.
      235 transplants were completed of which 190 were registered recipients and 45
      were from the deceased donor (DD) wait list. At 1 year, patient survival was
      100%, graft survival 98%, with a biopsy proven acute rejection rate of 8%. The
      mean serum creatinine (Cr) at the end of one year was 109 mmol/l. Donor survival
      is 100%. Key to success are national standards for antibody testing and cross
      matching, and for evaluating donors and recipients, as well infrastructure
      (software and personnel) to run the program. The structure of the Canadian
      program is compared with that of other programs in the United Kingdom, Australia,
      the Netherlands, and the United States. LIMITATIONS: This review does not include
      information on travel distances and difficulties, or patient satisfaction.
      IMPLICATIONS: National collaboration and acceptance of common standards is
      possible and leads to substantial benefits, especially for those patients who are
      hardest to match. What was known before: Kidney paired donation is considered
      ethically acceptable. National and regional programs have been created in a
      number of countries. WHAT THIS PAPER ADDS: Key to the success of the Canadian
      national program are acceptance of standardized procedures and national and
      provincial support and oversight.

PMID- 25780602
TI  - Incentives and organ donation: what's (really) legal in Canada?
AB  - PURPOSE OF REVIEW: To date, there has been little analysis of the degree to which
      emerging incentive initiatives are permissible under Canadian law. The purpose of
      this review is to examine the relevant law - including legislation and case law -
      in order to clarify the legality of existing proposed incentive schemes. SOURCES
      OF INFORMATION: Legislation and case law. FINDINGS: Organ donation is governed by
      provincial legislation that, in general, bans the exchange of any "benefit" or
      any form of "valuable consideration" in return for an organ. As such, these laws
      are tremendously restrictive and could have significant implications for emerging
      and proposed procurement policy. IMPLICATIONS: Given the need for innovative,
      ethically appropriate policies to increase donation rates, we suggest that the
      time is right to rethink the potentially restrictive nature of Canada's organ
      donation laws.

PMID- 25780603
TI  - Is the Canadian legal framework too restrictive and based on false premises?

PMID- 25780604
TI  - Evaluating the implementation strategy for estimated glomerular filtration rate
      reporting in Manitoba: the effect on referral numbers, wait times, and
      appropriateness of consults.
AB  - BACKGROUND: Chronic kidney disease screening using estimated glomerular
      filtration rate (eGFR) reporting is standard in many regions. With its
      implementation, many centres have had higher referral rates and increased wait
      times to see nephrologists. OBJECTIVE: Manitoba began eGFR reporting in October
      2010. We measured the effect of eGFR reporting on referral rates, wait times, and
      appropriateness of referrals after an educational intervention. DESIGN: An
      interrupted time series design was used. SETTING: This study took place in
      Manitoba, Canada. PATIENTS: All referrals to the Manitoba Renal Program in the
      period prior to eGFR reporting between April 1, 2010 and September 30, 2010 were
      compared with a post period between January 1, 2011 and June 30, 2011.
      MEASUREMENTS: Data on demographics, co-morbidities, referral numbers and wait
      times were compared between periods. Appropriateness of consults was also
      measured after eGFR implementation. METHODS: Prior to eGFR reporting, primary
      care physicians underwent educational interventions on eGFR interpretation and
      referral guidelines. Referral rates and wait times were compared between periods
      using generalized linear models. Chart audits of a random sample of 232 patients
      in the pre period and 239 patients in the post period were performed. RESULTS:
      The pre and post eGFR reporting referral rate was 116 and 152 referrals/month,
      respectively. Average wait times in the pre and post eGFR reporting was 113 and
      115 days, respectively. Non-urgent referral wait times increased by 40 days
      immediately post reporting, while urgent median referral wait times had a more
      gradual increase. Despite our intervention, inappropriate consultations post eGFR
      reporting was 495/790 (62.7%). LIMITATIONS: Our study did not measure the
      intervention's success on primary care providers, which may have affected our
      appropriateness data. Our time series design was not powered to find a
      statistically significant difference in referral numbers. Residual confounding of
      our results was possible given the retrospective nature of our study. CONCLUSION:
      Despite our educational intervention, the inappropriate referrals remained high,
      and wait times increased. Other systemic interventions should be considered to
      attenuate the potential negative effects of eGFR reporting and ensure timely
      access for patients needing specialist consultation.

PMID- 25780605
TI  - Mortality risk for women on chronic hemodialysis differs by age.
AB  - BACKGROUND: Previous reports have demonstrated similar survival for men and women
      on hemodialysis, despite women's increased survival in the general population.
      OBJECTIVES: To examine the effect of age on mortality in women undergoing chronic
      hemodialysis. DESIGN: A retrospective cohort study using an administrative data
      registry, the Canadian Organ Replacement Registry (CORR) from Jan. 2001 and Dec.
      2009. SETTING: Canada. PATIENTS: 28,971 (Women 11,792 (40.7%), Men 17,179
      (59.3%)) incident chronic hemodialysis patients who survived greater than 90 days
      on dialysis. MEASUREMENTS: All-cause mortality. METHODS: Cox proportional hazards
      and competing risks models were employed to determine the independent association
      between sex, age and likelihood of all-cause mortality with renal transplantation
      as the competing outcome. RESULTS: During the study period, 6060 (51.4%) of women
      and 8650 (50.4%) of men initiating dialysis died. Younger women experienced
      higher mortality (Age < 45: Women 22.5%, Men 18.2%, hazard ratio (HR) 1.31 (1.12
      1.52)) whereas elderly women experience lower mortality (Age 75-85: Women 65%,
      Men 67.3%, HR 0.94 95% CI 0.88-0.99, Age > 85: Women 66%, Men 70.2%, HR 0.83 95%
      CI 0.71-0.97) compared to men. This relationship persisted after accounting for
      the competing risk of transplantation. LIMITATIONS: The cause of death was
      unknown. CONCLUSIONS: Women's survival on chronic hemodialysis varies by age
      compared to men with a significantly higher mortality in women younger than 45
      years old and lower mortality in woman older than 75 years of age.

PMID- 25780606
TI  - Programmatic variation in home hemodialysis in Canada: results from a nationwide
      survey of practice patterns.
AB  - BACKGROUND: Over 40% of patients with end stage renal disease in the United
      States were treated with home hemodialysis (HHD) in the early 1970's. However,
      this number declined rapidly over the ensuing decades so that the overwhelming
      majority of patients were treated in-centre 3 times per week on a 3-4 hour
      schedule. Poor outcomes for patients treated in this fashion led to a renewed
      interest in home hemodialysis, with more intensive dialysis schedules including
      short daily (SDHD) and nocturnal (NHD). The relative infancy of these treatment
      schedules means that there is a paucity of data on 'how to do it'. OBJECTIVE: We
      undertook a systematic survey of home hemodialysis programs in Canada to describe
      current practice patterns. DESIGN: Development and deployment of a qualitative
      survey instrument. SETTING: Community and academic HHD programs in Canada.
      PARTICIPANTS: Physicians, nurses and technologists. MEASUREMENTS: Programmatic
      approaches to patient selection, delivery of dialysis, human resources available,
      and follow up. METHODS: We developed the survey instrument in three phases. A
      focus group of Canadian nephrologists with expertise in NHD or SDHD discussed the
      scope the study and wrote questions on 11 domains. Three nephrologists familiar
      with all aspects of HHD delivery reviewed this for content validity, followed by
      further feedback from the whole group. Multidisciplinary teams at three sites
      pretested the survey and further suggestions were incorporated. In July 2010 we
      distributed the survey electronically to all renal programs known to offer HHD
      according to the Canadian Organ Replacement Registry. We compiled the survey
      results using qualitative and quantitative methods, as appropriate. RESULTS: Of
      the academic and community programs that were invited to participate, 80% and
      63%, respectively, completed the survey. We observed wide variation in
      programmatic approaches to patient recruitment, human resources, equipment,
      water, vascular access, patient training, dialysis prescription, home
      requirements, patient follow up, medications, and the approach to non-adherent
      patients. LIMITATIONS: Cross-sectional survey, unable to link variation to
      outcomes. Competition for patients between HHD and home peritoneal dialysis means
      that case mix for HHD may also vary between centres. CONCLUSIONS: There is wide
      variation between programs in all domains of HHD delivery in Canada. We plan
      further study of the extent to which differences in approach are related to
      outcomes.

PMID- 25780607
TI  - Estimation of total glomerular number using an integrated disector method in
      embryonic and postnatal kidneys.
AB  - Congenital Anomalies of the Kidney and Urinary Tract (CAKUT) are a polymorphic
      group of clinical disorders comprising the major cause of renal failure in
      children. Included within CAKUT is a wide spectrum of developmental malformations
      ranging from renal agenesis, renal hypoplasia and renal dysplasia
      (maldifferentiation of renal tissue), each characterized by varying deficits in
      nephron number. First presented in the Brenner Hypothesis, low congenital nephron
      endowment is becoming recognized as an antecedent cause of adult-onset
      hypertension, a leading cause of coronary heart disease, stroke, and renal
      failure in North America. Genetic mouse models of impaired nephrogenesis and
      nephron endowment provide a critical framework for understanding the origins of
      human kidney disease. Current methods to quantitate nephron number include (i)
      acid maceration (ii) estimation of nephron number from a small number of tissue
      sections (iii) imaging modalities such as MRI and (iv) the gold standard physical
      disector/fractionator method. Despite its accuracy, the physical
      disector/fractionator method is rarely employed because it is labour-intensive,
      time-consuming and costly to perform. Consequently, less rigourous methods of
      nephron estimation are routinely employed by many laboratories. Here we present
      an updated, digitized version of the physical disector/fractionator method using
      free open source Fiji software, which we have termed the integrated disector
      method. This updated version of the gold standard modality accurately, rapidly
      and cost-effectively quantitates nephron number in embryonic and post-natal mouse
      kidneys, and can be easily adapted for stereological measurements in other organ
      systems. 

PMID- 25780608
TI  - Assessment of potential biomarkers of subclinical vitamin K deficiency in
      patients with end-stage kidney disease.
AB  - BACKGROUND: A significant proportion of hemodialysis patients have functional,
      but modifiable, vitamin K deficiency. OBJECTIVE: To determine the correlates of
      poor vitamin K status in hemodialysis patients. DESIGN: Cross-sectional study.
      SETTING: Hemodialysis units at Kingston General Hospital and its satellite
      centres, Ontario, Canada. PATIENTS: Patients undergoing outpatient hemodialysis
      for end-stage kidney disease. MEASUREMENTS: Serum concentrations of
      phylloquinone, undercarboxylated prothrombin, also known as protein induced by
      vitamin K absence or antagonism - factor II (PIVKA-II), and the percentage of
      undercarboxylated osteocalcin (%ucOC). METHODS: Vitamin K status was determined
      in fasting blood samples of hemodialysis patients. Bivariate relationships were
      examined using parametric and non-parametric statistics as appropriate.
      Multivariable linear regression models were applied to identify predictors of
      vitamin K status. RESULTS: Among 44 HD patients, criteria for subclinical vitamin
      K deficiency were met in 13.6% (phylloquinone < 0.4 nmol/L), 51% (%ucOC > 20%)
      and 90.9% (PIVKA-II > 2.0 nmol/L) of subjects. Phylloquinone levels were
      positively associated with total cholesterol, triglyceride levels and non-smoking
      status. Higher %ucOC was associated with increased calcium-phosphate product.
      Increased PIVKA-II levels were observed with advancing age, reduced dialysis
      adequacy, lower HDL and a history of coronary artery disease. There were no
      associations found among the individual biomarkers of vitamin K status. In a
      multi-variable model, triglycerides were the only significant predictor of
      phylloquinone levels, while increasing phosphate and decreasing PTH were
      independent predictors of %ucOC. PIVKA-II levels increased by 0.54 nmol/L for
      every 10-year increase in age. LIMITATIONS: Observational study; small sample
      size. CONCLUSIONS: A significant proportion of HD patients met criteria for
      subclinical vitamin K deficiency. Of the biomarkers measured, PIVKA-II may be
      superior given its independence of renal function or dyslipidemia, both of which
      may confound the other vitamin K biomarkers. Studies in patients with ESKD
      linking biomarkers of vitamin K status to important patient outcomes, including
      cardiovascular disease, nutritional status and mortality, are required in order
      to determine the optimal biomarker for evaluating vitamin K status in this
      particular population.

PMID- 25780609
TI  - Cost analysis of in-centre nocturnal compared with conventional hemodialysis.
AB  - BACKGROUND: Provision of in-centre nocturnal hemodialysis (ICNHD; 6-8 hours
      thrice weekly) is associated with health benefits, but the economic implications
      of providing this treatment are unclear. OBJECTIVE: We conducted a health care
      costing study comparing ICNHD to in-centre thrice-weekly conventional
      hemodialysis (CvHD). DESIGN: Micro-costing of both ICNHD and CvHD as practiced at
      our centre. SETTING: Hemodialysis unit at a tertiary-care hospital in Edmonton.
      PARTICIPANTS: An informal survey of 2 other Canadian ICNHD programs was conducted
      to inform practices that may deviate from ours to guide sensitivity analysis.
      MEASUREMENTS: Resources consumed for each strategy were determined, and the cost
      of each unit (CAN $2012) was used to calculate incremental costs of ICNHD and
      CvHD. METHODS: We focused on resources that differ between strategies (staffing,
      dialysis materials, and utilities). The reference case considered 1:3 staff to
      patient ratio; alternate scenarios explored nursing pay grade and ratio, full
      care vs. self-care dialysis (including training costs), and medication costs.
      RESULTS: In the reference case, ICNHD was $61 more costly per dialysis treatment
      compared with CvHD ($9,538 per patient per year). Incremental annual costs for
      staffing, dialysis materials, and utilities were $8,201, $1,193, and $144,
      respectively. If ICNHD reduces medication use (anti-hypertensives, bone mineral
      metabolism medications), the incremental cost of ICNHD decreases to $8,620 per
      patient per year. In a scenario of self-care ICNHD utilizing a staff-to-patient
      ratio of 1:10, ICNHD is more costly in year 1 ($15,196), but results in cost
      savings of $2,625 in subsequent years compared with CvHD. LIMITATIONS: The
      findings of this cost analysis may not be generalizable to other health care
      systems, including other parts of Canada. CONCLUSIONS: Compared to CvHD,
      provision of ICNHD is more expensive, largely driven by increased staffing costs
      as patients dialyze longer. Alternate staffing models, including self-care ICNHD
      with minimal staff, may lead to net cost savings. The incremental cost of
      treatment should be considered in the context of impact on patient health
      outcomes, staffing model, and pragmatic factors, such as current capacity for
      daytime CvHD and the capital costs of new dialysis stations.

PMID- 25780610
TI  - Bridging the gap: a Canadian perspective on translational kidney research.
AB  - PURPOSE OF REVIEW: Chronic kidney disease affects approximately 3 million
      Canadians. Ongoing investment in high quality kidney research is needed to
      improve the care of patients with kidney disease. The barriers to translating
      such research are discussed in this review. SOURCES OF INFORMATION: Personal
      knowledge, research funding body websites, and published reports. FINDINGS: In
      this review, we discuss the meaning of the term translational research and
      present some of the programs aimed at ensuring efficient translation of
      scientific discoveries with a discussion of the barriers to translation. We
      highlight some successes and barriers to kidney research translation using recent
      examples of research in Canadian nephrology. We present the following examples of
      kidney research: (1) research aimed at identifying the causative genes for
      inherited kidney diseases; (2) recent discoveries in cell-based therapies for
      kidney disease; (3) an examination of the impact of acute kidney injury in renal
      transplant patients; and (4) the development of a kidney failure risk equation to
      improve prognosis accuracy. LIMITATIONS: This review focuses on research
      conducted by the authors. IMPLICATIONS: The process of research translation is
      prolonged and challenging and therefore requires resources, patience, and careful
      planning. With increased awareness and understanding of the barriers to research
      translation, researchers and funding bodies can work together to increase the
      rate at which important research findings reach clinical practice and improve the
      care of patients with kidney disease.

PMID- 25780611
TI  - The three-year incidence of major hemorrhage among older adults initiating
      chronic dialysis.
AB  - BACKGROUND: For those who initiate chronic dialysis, knowing what proportion will
      experience 3-year outcomes of hemorrhage with hospitalization informs patient
      prognosis, disease impact, and the planning of trials and programs to prevent
      events. OBJECTIVES: We examined the incidence of hemorrhage and related
      gastrointestinal endoscopic procedures in incident older dialysis patients and
      stratified patients by age, era, dialysis modality and whether recently
      prescribed anti-thrombotic medication. DESIGN: Retrospective cohort study.
      SETTING: Ontario, Canada from 1998 to 2008 (n = 11,173). PATIENTS: All older
      patients (>65 years) who initiated chronic dialysis. MEASUREMENTS:
      Hospitalization with hemorrhage and its subtypes (upper and lower
      gastrointestinal, intra-cerebral, subarachnoid) and related-gastrointestinal
      procedures. METHODS: Three-year outcomes of hospitalization with hemorrhage were
      expressed as cumulative incidence and incidence rate (number of events per 1,000
      patient years). Results were stratified by patient age (66 to 74, 75 to 84, >=
      85), era (1998 to 2001, 2002 to 2005, 2006 to 2008) and dialysis modality. Among
      those with hemorrhage, we examined prescriptions for anti-thrombotic medications
      (warfarin, clopidogrel) in the preceding 120 days. RESULTS: The 3-year cumulative
      incidence of hemorrhage was 14.4% (roughly 1 in 7 patients). By location, the 3
      year cumulative incidence was 8.9% lower gastrointestinal, 6.1% upper
      gastrointestinal, 0.9% intra-cerebral and 0.1% sub arachnoid hemorrhage. The 3
      year cumulative incidence of gastrointestinal endoscopic procedures was 14.8%.
      The cumulative incidence and rate of hemorrhage were not appreciably different
      across the 3 age strata, by era or by dialysis modality. Among patients with a
      hemorrhage, 29.5% were prescribed warfarin in the preceding 120 days, and 8.4%
      clopidogrel. LIMITATIONS: Recurrent events were not included. CONCLUSIONS: Many
      older patients who initiate chronic dialysis will be hospitalized with hemorrhage
      and receive related procedures over the subsequent three years. Despite greater
      age and co-morbidity over the last decade this incidence has not changed.

PMID- 25780612
TI  - Is it ethical to prescribe generic immunosuppressive drugs to renal transplant
      patients?
AB  - PURPOSE OF THE REVIEW: This review was conducted to determine the ethical
      acceptability of prescribing generic immunosuppressive drugs to renal transplant
      patients. SOURCES OF INFORMATION: The literature search was conducted using
      Pubmed and Google Scholar. FINDINGS: The use of generic immunosuppressive drugs
      (ISDs) in transplantation is a controversial topic. There is a consensus among
      transplant societies that clinical data is lacking and that caution should be
      exercised. The reluctance to use generic ISDs in organ transplantation is partly
      related to the fact that most are "critical dose drugs", and that either low
      dosing or overdosing could have serious adverse consequences for both patients
      and society (i.e., the loss of scarce organs). In this paper, we examine the
      various ethical issues involved such as distributive justice, physician duties,
      risks versus benefits, conflict of interest, informed consent, and logistical and
      economic issues. LIMITATIONS: Our analysis was limited by the paucity of clinical
      data on generic ISDs and the absence of health economics studies to quantify the
      benefits of prescribing generic ISDs. IMPLICATIONS: Our study led us to conclude
      that it would be ethical to prescribe generic ISDs provided certain conditions
      were met. These include regulatory safeguards to minimize the risks of
      substitution; education of patients; and further clinical and health economics
      studies to better inform clinicians, patients and society of the risks and costs
      related to drug substitution.

PMID- 25780613
TI  - Patient engagement and patient-centred care in the management of advanced chronic
      kidney disease and chronic kidney failure.
AB  - PURPOSE: The purpose of this article is to review the current status of patient
      centred care (PCC) and patient engagement (PE) in the management of patients with
      advanced chronic kidney disease (CKD) and end-stage renal disease (ESRD), to
      identify some of the barriers that exist to the achievement of PCC and PE, and to
      describe how these barriers can be overcome. SOURCES OF INFORMATION: The review
      is based on the professional experience of one of the authors (RB) as a
      Nephrologist and health care consultant, on the MBA thesis of one of the authors
      (SS) and on a review of pertinent internet-based information and published
      literature. FINDINGS: Evidence exists that, currently, the care of patients with
      advanced CKD and ESRD is not fully patient-centred or fully supportive of PE. A
      number of barriers exist, including: conflict with other priorities; lack of
      training and fear of change; the unequal balance of power between patients and
      providers; physician culture and behaviour; the fee-for-service model of
      physician compensation; slow implementation of electronic health records; and,
      fear of accountability. These barriers can be overcome by committed leadership
      and the development of an information-based implementation plan. Established
      Renal Agencies in Canada appear interested in facilitating this work by
      collaborating in the development of a toolkit of recommended educational
      resources and preferred implementation practices for use by ESRD Programs.
      LIMITATIONS: A limitation of this review is the absence of a substantial pre
      existing literature on this topic. IMPLICATIONS: Receiving care that is patient
      centred and that promotes PE benefits patients with serious chronic diseases such
      as advanced CKD and ESRD. Considerable work is required by ESRD Programs to
      ensure that such care is provided. Canadian Renal Agencies can play an important
      role by ensuring that ESRD Programs have access to essential educational material
      and proven implementation approaches and that implementation successes are
      celebrated. In this area, enabling policies are required, as are clinical
      research studies focusing on the measurement of outcomes.

PMID- 25780614
TI  - Use of a national continuing medical education meeting to provide simulation
      based training in temporary hemodialysis catheter insertion skills: a pre-test
      post-test study.
AB  - BACKGROUND: Simulation-based-mastery-learning (SBML) is an effective method to
      train nephrology fellows to competently insert temporary, non-tunneled
      hemodialysis catheters (NTHCs). Previous studies of SBML for NTHC-insertion have
      been conducted at a local level. OBJECTIVES: Determine if SBML for NTHC-insertion
      can be effective when provided at a national continuing medical education (CME)
      meeting. Describe the correlation of demographic factors, prior experience with
      NTHC-insertion and procedural self-confidence with simulated performance of the
      procedure. DESIGN: Pre-test - post-test study. SETTING: 2014 Canadian Society of
      Nephrology annual meeting. PARTICIPANTS: Nephrology fellows, internal medicine
      residents and medical students. MEASUREMENTS: Participants were surveyed
      regarding demographics, prior NTHC-insertion experience, procedural self
      confidence and attitudes regarding the training they received. NTHC-insertion
      skills were assessed using a 28-item checklist. METHODS: Participants underwent a
      pre-test of their NTHC-insertion skills at the internal jugular site using a
      realistic patient simulator and ultrasound machine. Participants then had a
      training session that included a didactic presentation and 2 hours of deliberate
      practice using the simulator. On the following day, trainees completed a post
      test of their NTHC-insertion skills. All participants were required to meet or
      exceed a minimum passing score (MPS) previously set at 79%. Trainees who did not
      reach the MPS were required to perform more deliberate practice until the MPS was
      achieved. RESULTS: Twenty-two individuals participated in SBML training. None met
      or exceeded the MPS at baseline with a median checklist score of 20 (IQR, 7.25 to
      21). Seventeen of 22 participants (77%) completed post-testing and improved their
      scores to a median of 27 (IQR, 26 to 28; p < 0.001). All met or exceeded the MPS
      on their first attempt. There were no significant correlations between
      demographics, prior experience or procedural self-confidence with pre-test
      performance. LIMITATIONS: Small sample-size and self-selection of participants.
      Costs could limit the long-term feasibility of providing this type of training at
      a CME conference. CONCLUSIONS: Despite most participants reporting having
      previously inserted NTHCs in clinical practice, none met the MPS at baseline;
      this suggests their prior training may have been inadequate.

PMID- 25780615
TI  - Canadian Organ Replacement Register (CORR): reflecting the past and embracing the
      future.
AB  - INTRODUCTION: The Canadian Organ Replacement Register (CORR) is the only Canadian
      information system on kidney and extra-kidney organ failure and transplantation
      in Canada. CORR's mandate is to record and analyze the level of activity and
      outcomes of vital organ transplantation and treatment of end stage kidney disease
      using dialysis, either hemodialysis or peritoneal dialysis, activities across
      Canada. The Canadian Organ Replacement Register was officially launched in 1987,
      and it included transplantation of extra-renal vital organs (liver, heart, lung,
      pancreas, bowel), in addition to renal transplantation and replacement therapy,
      with new financial support from the provinces. OBJECTIVE: This manuscript
      describes the process of data acquisition and reporting, focusing on the patients
      with end stage kidney disease on dialysis, with data reported from the 2014 CORR
      Annual Data Report and the Center-Specific Reports on Clinical Measures. METHODS:
      CORR is currently housed in the Canadian Institute for Health Information and
      collects data from hospital dialysis programs, regional transplant programs,
      organ procurement organizations and kidney dialysis services offered at
      independent health facilities. Data on patients is collected by completion of
      survey forms for each patient at the start of dialysis or receiving a transplant,
      using the Initial Registration form, and yearly follow up forms, which collects
      data on the status of the patient as of October 31(st). RESULTS: The incident
      rate per million population (RPMP) has remained stable with the exception of the
      65+ age group with has experience a modest decrease since 2001. However, there
      has been an increasing prevalence of ESKD diagnoses, with the highest rate per
      million population (RPMP) amongst the age group 65+ years. This is likely
      attributed to gradual improving patient survival. Between 2003 and 2012, nearly
      90% of dialysis patients younger than <18 and 26% of patients 75+ years survived
      for at least five years. CONCLUSION: As the number of people treated for end
      stage organ failure grows, so does the importance of understanding their
      treatment and outcomes. In 2014, CORR continues to evolve and support the
      important information need to advance ESRD research and clinical practice.

PMID- 25780616
TI  - Health care prioritization: a clinician's duty.
AB  - PURPOSE OF REVIEW: Publicly funded health care systems are increasingly
      confronted with fiscal and demographic challenges and face pressure to constrain
      resource use without impacting clinical outcomes. FINDINGS: Clinicians routinely
      make decisions in the care of their patients that use finite health care
      resources. Aligning the goal of caring for their patients with ensuring that
      effective interventions are available for patients who are most likely to benefit
      is critical to sustaining the publicly funded health care system. IMPLICATIONS:
      Balancing the needs of patients with health care prioritization will require
      changes to be made across the health care system. Incorporating costs and value
      for money when caring for patients and making decisions will play an important
      role in efficiency and value in the health system.

PMID- 25780617
TI  - A budget impact analysis of the introduction of erythropoiesis stimulating agent
      subsequent entry biologics for the treatment of anemia of chronic kidney disease
      in Canada.
AB  - BACKGROUND: In Europe, epoetin subsequent entry biologics (SEBs) have been in use
      since 2007. Canadian patents of erythropoietin stimulating agents are expiring in
      2014, therefore it is predicted that epoetin SEBs will penetrate the Canadian
      market in the near future. OBJECTIVE: To estimate the economic impact and costs
      offsets associated with the uptake and use of one or more epoetin SEBs in Canada
      for the treatment of anemia in chronic kidney disease. DESIGN: A Canada-wide
      epidemiological-based budget impact analysis was conducted to estimate cost
      outcomes under two scenarios: with and without the availability of epoetin SEB.
      SETTING: The analysis was conducted from the perspective of the Canadian
      healthcare payer, over a 5-year time horizon from 2015 to 2019. PATIENTS:
      Patients included in the model were those with chronic kidney disease stages 3 to
      5, who have renal anemia and require treatment with erythropoietin stimulating
      agents. METHODS: Only direct medical costs pertaining to drug acquisition of
      currently available erythropoietin stimulating agents in Canada were incorporated
      in the model. Cost of epoetin SEBs, market shares, uptake rates, and other model
      inputs were estimated from published sources or databases. No discounting of
      future costs was applied. RESULTS: Based on our analysis, under market phenomena
      similar to those seen in the Europe and without considering potential switching
      from originator epoetin to epoetin SEB, we could expect that Canadian adoption of
      epoetin SEBs could result in $35 million (2013 CAD, year 1) to $50 million (year
      5) cost savings annually, with cumulative savings of $221 million after 5 years.
      In one-way sensitivity analyses, model variables with substantial impact on cost
      savings were the prevalence of chronic kidney disease and epoetin SEB uptake
      rates. LIMITATIONS: We did not take into account costs associated with overhead,
      administration, or adverse events. CONCLUSION: The advent of SEBs represents an
      opportunity to relieve financial pressure in our healthcare system. Under the
      assumption that the efficacy and safety of epoetin SEBs are non-inferior to
      originator products, we have shown that the adoption of epoetin SEBs can lead to
      cost savings for the Canadian payer.

PMID- 25780618
TI  - Canadian chronic kidney disease clinics: a national survey of structure, function
      and models of care.
AB  - BACKGROUND: The goals of care for patients with chronic kidney disease (CKD) are
      to delay progression to end stage renal disease, reduce complications, and to
      ensure timely transition to dialysis or transplantation, while optimizing
      independence. Recent guidelines recommend that multidisciplinary team based care
      should be available to patients with CKD. While most provinces fund CKD care, the
      specific models by which these outcomes are achieved are not known. Funding for
      clinics is hospital or program based. OBJECTIVES: To describe the structure and
      function of clinics in order to understand the current models of care, inform
      best practice and potentially standardize models of care. DESIGN: Prospective
      cross sectional observational survey study. SETTING PATIENTS/PARTICIPANTS:
      Canadian nephrology programs in all provinces. METHODS AND MEASUREMENTS: Using an
      open-ended semi-structured questionnaire, we surveyed 71 of 84 multidisciplinary
      adult CKD clinics across Canada, by telephone and with written semi-structured
      questionnaires; (June 2012 to November 2013). Standardized introductory scripts
      were used, in both English and French. RESULTS: CKD clinic structure and models
      of care vary significantly across Canada. Large variation exists in staffing
      ratios (Nephrologist, dieticians, pharmacists and nurses to patients), and in
      referral criteria. Dialysis initiation decisions were usually made by MDs. The
      majority of clinics (57%) had a consistent model of care (the same Nephrologist
      and nurse per patient), while others had patients seeing a different nephrologist
      and nurses at each clinic visit. Targets for various modality choices varied, as
      did access to those modalities. No patient or provider educational tools
      describing the optimal time to start dialysis exist in any of the clinics.
      LIMITATIONS: The surveys rely on self reporting without validation from
      independent sources, and there was limited involvement of Quebec clinics. These
      are relative limitations and do not affect the main results. CONCLUSIONS: The
      variability in clinic structure and function offers an opportunity to explore the
      relationship of these elements to patient outcomes, and to determine optimal
      models of care. This list of contacts generated through this study, serves as a
      basis for establishing a CKD clinic network. This network is anticipated to
      facilitate the conduct of clinical trials to test novel interventions or
      strategies within the context of well characterized models of care.

PMID- 25780620
TI  - Organ donation and transplantation in Canada: insights from the Canadian Organ
      Replacement Register.
AB  - PURPOSE OF REVIEW: To provide an overview of the transplant component of the
      Canadian Organ Replacement Register (CORR). FINDINGS: CORR is the national
      registry of organ failure in Canada. It has existed in some form since 1972 and
      currently houses data on patients with end-stage renal disease and solid organ
      transplants (kidney and/or non-kidney). The transplant component of CORR receives
      data on a voluntary basis from individual transplant centres and organ
      procurement organizations across the country. Coverage for transplant procedures
      is comprehensive and complete. Long-term outcomes are tracked based on follow-up
      reports from participating transplant centres. The longitudinal nature of CORR
      provides an opportunity to observe the trajectory of a patient's journey with
      organ failure over their life span. Research studies conducted using CORR data
      inform both practitioners and health policy makers alike. IMPLICATIONS: The
      importance of registry data in monitoring and improving care for Canadian
      transplant candidates/recipients cannot be over-stated. This paper provides an
      overview of the transplant data in CORR including its history, data
      considerations, recent findings, new initiatives, and future directions.

PMID- 25780619
TI  - The Steroids In the Maintenance of remission of Proliferative Lupus nephritis
      (SIMPL) pilot trial.
AB  - BACKGROUND: Patients with proliferative lupus nephritis are at risk of frequent
      relapses. Whether low- dose prednisone prevents relapses is uncertain.
      OBJECTIVES: We undertook a pilot RCT to determine the feasibility of a larger
      trial. DESIGN: Pilot randomized controlled trial. SETTING: Single center Canadian
      outpatient nephrology clinic. PATIENTS: Participants with systemic lupus
      erythematosus (SLE) and a history of class III or IV lupus nephritis that
      achieved at least partial remission and remained on prednisone were eligible.
      MEASUREMENTS: Feasibility: proportion of eligible patients randomized and
      adherence to tapering regimen. Clinical: occurrence of renal or major non-renal
      flare of SLE. METHODS: We conducted a blinded, two-parallel-group randomized
      controlled trial of prednisone 7.5 mg/day (continuation) compared to a matching
      placebo (withdrawal). RESULTS: Of nineteen eligible patients screened, 15 (79%)
      were recruited and randomized; 8 to prednisone continuation and seven to
      withdrawal. All participants adhered to the tapering protocol to their assigned
      withdrawal or low-dose maintenance target. Over 36 months, the primary outcome
      occurred in four (50%) patients in the continuation group (three renal and one
      major non-renal flare), compared with one patient (14%) in the withdrawal group
      (one renal flare). Three participants (38%) in the continuation group had minor
      flares, while no patients in the withdrawal group did. LIMITATIONS: This pilot
      RCT was small and not designed to assess the efficacy or safety of maintenance
      with low-dose prednisone. CONCLUSIONS: The high proportion of eligible patients
      recruited, and success of protocol adherence suggest a large trial of prednisone
      maintenance therapy compared to withdrawal is feasible. TRIAL REGISTRATION:
      Current Controlled Trials ISRCTN31327267.

PMID- 25780621
TI  - Potential impact of subsequent entry biologics in nephrology practice in Canada.
AB  - PURPOSE OF REVIEW: Subsequent entry biologics may soon be a reality in Canadian
      nephrology practice. Along with opportunities to reduce health care costs, these
      agents pose unique challenges that must be met for successful implementation.
      Understanding the experiences around the globe in both regulatory affairs and
      implementation will be a valuable guide for Canadian clinicians. This report
      provides an executive summary of the information required to guide decisions to
      use or implement subsequent entry biologics by comparing Canadian regulations to
      other developed nations, discussing their clinical issues and predicting their
      impact on the Canadian market and nephrology practice. We hope that this review
      will assist clinicians and policy makers to navigate this complex subject and to
      make informed decisions in the best interest of their patients. SOURCES OF
      INFORMATION: Sources of information include published literature and reports
      available in the public domain including guidelines obtained from regulatory
      agencies and information shared by Pharmaceutical companies. Lastly, we generated
      information from our own focus group consisting of nephrologists, a regulatory
      body representative, a hospital formulary representative, a patient
      representative, a hospital administrator, and a health economist. FINDINGS: There
      exists a common and robust approach in the G20 countries for approval and
      regulation of subsequent entry biologics. Although by definition these agents do
      not have advantages (other than costs) or disadvantages compared to the original
      biologic, there are potential concerns and economic uncertainties regarding their
      implementation. Where SEBs are on the market, their market share is variable and
      modest. LIMITATIONS: We did not purchase third party reports for up to the minute
      marketing data. Since there are no subsequent entry biologics currently on the
      Canadian market, the information is only predictive. IMPLICATIONS: The nephrology
      community will have to work with patients, payers, and regulatory bodies to
      ensure safe and effective use of subsequent entry biologics. Cost savings can be
      achieved but these agents should only be used after fully understanding their
      unique challenges. At this time, they should not be automatically substitutable
      and only used for Health Canada-approved indications. Only through good
      pharmacovigilence will health care providers and patients become better informed.

PMID- 25780622
TI  - Kidney function, albuminuria and life expectancy.
AB  - BACKGROUND: Lower estimated glomerular filtration rate is associated with reduced
      life expectancy. Whether this association is modified by the presence or absence
      of albuminuria, another cardinal finding of chronic kidney disease, is unknown.
      OBJECTIVE: Our objective was to estimate the life expectancy of middle-aged men
      and women with varying levels of eGFR and concomitant albuminuria. DESIGN: A
      retrospective cohort study. SETTING: A large population-based cohort identified
      from the provincial laboratory registry in Alberta, Canada. PARTICIPANTS: Adults
      aged >=30 years who had outpatient measures of serum creatinine and albuminuria
      between May 1, 2002 and March 31, 2008. MEASUREMENTS:  PREDICTOR: Baseline levels
      of kidney function identified from serum creatinine and albuminuria measurements.
      OUTCOMES: all cause mortality during the follow-up. METHODS: Patients were
      categorized based on their estimated glomerular filtration rate (eGFR) (>=60, 45
      59, 30-44, and 15-29 mL/min/1 . 73 m(2)) as well as albuminuria (normal, mild,
      and heavy) measured by albumin-to-creatinine ratio or urine dipstick. The
      abridged life table method was applied to calculate the life expectancies of men
      and women from age 40 to 80 years across combined eGFR and albuminuria
      categories. We also categorized participants by severity of kidney disease (low
      risk, moderately increased risk, high risk, and very high risk) using the
      combination of eGFR and albuminuria levels. RESULTS: Among men aged 50 years and
      with eGFR >=60 mL/min/1.73 m(2), estimated life expectancy was 24.8 (95% CI: 24.6
      25.0), 17.5 (95% CI: 17.1-17.9), and 13.5 (95% CI: 12.6-14.3) years for
      participants with normal, mild and heavy albuminuria respectively. Life
      expectancy for men with mild and heavy albuminuria was 7.3 (95% CI: 6.9-7.8) and
      11.3 (95% CI: 10.5-12.2) years shorter than men with normal proteinuria,
      respectively. A reduction in life expectancy was associated with an increasing
      severity of kidney disease; 24.8 years for low risk (95% CI: 24.6-25.0), 19.1
      years for moderately increased risk (95% CI: 18.7-19.5), 14.2 years for high risk
      (95% CI: 13.5-15.0), and 9.6 years for very high risk (95% CI: 8.4-10.8). Among
      women of similar age and kidney function, estimated life expectancy was 28.9 (95%
      CI: 28.7-29.1), 19.8 (95% CI: 19.2-20.3), and 14.8 (95% CI: 13.5-16.0) years for
      participants with normal, mild and heavy albuminuria respectively. Life
      expectancy for women with mild and heavy albuminuria was 9.1 (95% CI: 8.5-9.7)
      and 14.2 (95% CI: 12.9-15.4) years shorter than the women with normal
      proteinuria, respectively. For women also a graded reduction in life expectancy
      was observed across the increasing severity of kidney disease; 28.9 years for low
      risk (95% CI: 28.7-29.1), 22.5 years for moderately increased risk (95% CI: 22.0
      22.9), 16.5 years for high risk (95% CI: 15.4-17.5), and 9.2 years for very high
      risk (95% CI: 7.8-10.7). LIMITATIONS: Possible misclassification of long-term
      kidney function categories cannot be eliminated. Possibility of confounding due
      to concomitant comorbidities cannot be ruled out. CONCLUSION: The presence and
      degree of albuminuria was associated with lower estimated life expectancy for
      both gender and was especially notable in those with eGFR >=30 mL/min/1.73 m(2).
      Life expectancy associated with a given level of eGFR differs substantially based
      on the presence and severity of albuminuria.

PMID- 25780623
TI  - Efficacy and safety data of subsequent entry biologics pertinent to nephrology
      practice: a systematic review.
AB  - BACKGROUND: Subsequent entry biologics (SEBs) may soon be a reality in Canadian
      nephrology practice. Understanding the worldwide experience with these agents
      will be valuable to Canadian clinicians. OBJECTIVES: To compare the efficacy and
      safety data between SEBs used in nephrology practice and their reference
      biologic. DESIGN: Systematic review. SOURCES OF INFORMATION: Ovid MEDLINE,
      EMBASE, Cochrane Database of Systematic Reviews, Database of Abstracts of Review
      of Effects, Cochrane Central Register of Controlled Trials. PATIENTS: Adult
      patients with chronic kidney disease (CKD). METHODS: Our systematic review
      follows the process outlined by Cochrane Reviews. For efficacy data, all
      randomized controlled trials (RCTs), quasi-RCTs and observational trials in
      nephrology practice were included. For safety data, case series, case reports,
      review articles in nephrology practice and pharmacovigilance programs were
      included as well. RESULTS: Only epoetin SEBs trials were published in the
      literature. Ten studies involving three different epoetin SEBs (epoetin zeta,
      HX575 and epoetin theta) were included. The mean epoetin dose used did not differ
      significantly between the SEBs and the reference product. For epoetin zeta and
      epoetin theta, the mean hemoglobin levels achieved in the studies were similar
      between the SEBs and the reference epoetin. The HX 575 studies reported a mean
      absolute change in hemoglobin within the predefined equivalence margin, when
      compared with the reference biologic. In terms of safety data, 2 cases of pure
      red-cell aplasia were linked to the subcutaneous administration of HX 575.
      Otherwise, the rate of adverse drug reactions was similar when epoetin SEBs were
      compared with the reference biologic. LIMITATIONS: Our analysis is limited by the
      paucity of information available on SEB use in nephrology with the exception of
      epoetin SEBs. Methodological flaw was found in one of the epoetin zeta studies
      which accounted for 45% of pooled results. CONCLUSIONS: Little clinical
      difference was found between epoetin SEBs and the reference product. Although not
      deemed clinically important, the financial implication of a possible dose
      difference between epoetin zeta and reference product should be considered in
      pharmacoeconomic studies. Ongoing trials are expected to address the risk of pure
      red-cell aplasia with HX 575.

PMID- 25780624
TI  - Urinary monocyte chemoattractant protein-1 levels and interstitial changes in the
      renal cortex and their relationship with loss of renal function in renal
      transplant patients with delayed graft function.
AB  - BACKGROUND: Inflammatory cell infiltration and residual areas of fibrosis in
      kidneys after renal transplantation can lead to functional abnormalities with
      long-term implications. OBJECTIVES: The aim of this study was to determine
      urinary monocyte chemoattractant protein-1 (uMCP-1) levels, relative cortical
      interstitial area (RCIA), and cortical tubulointerstitial macrophage infiltration
      in renal transplant patients with delayed graft function (DGF) and their possible
      correlation with graft outcome. DESIGN: Patients were followed after biopsies for
      one year, and their renal function and structure were evaluated, as well as
      parameters of inflammatory process. SETTING: Clinical Hospital of the School of
      Medicine of Ribeirao Preto. PATIENTS: Twenty-two cadaveric kidney transplant
      recipients with DGF were followed for one year. MEASUREMENTS: Renal function,
      RCIA, macrophages infiltration and uMCP-1 levels were evaluated. METHODS: Renal
      function was evaluated by plasma creatinine levels. RCIA was determined by
      morphometry. Immunohistochemical staining of macrophages was performed using an
      anti-CD68 monoclonal antibody. uMCP-1 levels were determined using a human MCP
      1/CCL2 immunoassay kit. RESULTS: There was a significant increase in uMCP-1
      levels in transplant patients compared with controls (p < 0.001). RCIA was 7.1%
      (6.4 to 9.2; median and 25th to 75th percentiles) in controls and 37.1% (28.1 to
      43.7) in patients with kidney transplants (p < 0.001). The patients who presented
      with a higher RCIA in the first biopsy showed higher levels of plasma creatinine
      one year after transplantation (r = 0.44; p < 0.05). The number of
      tubulointerstitial macrophages per 0.10 mm(2) grid field was higher in the renal
      cortex of transplant patients compared with the controls (19.4 (9.0 to 47.1) vs.
      2.5 (1.8 to 3.4), p < 0.001). There was also a positive correlation between the
      RCIA and the number of tubulointerstitial macrophages in the renal cortex of
      these patients (r = 0.49; p < 0.001). LIMITATIONS: The number of patients studied
      was relatively small and may not be reflecting outcomes over a larger spectrum of
      kidney cadaveric transplants. CONCLUSIONS: Our results demonstrate increased
      levels of uMCP-1 in transplant patients with DGF, in addition to increased
      tubulointerstitial macrophage infiltration and RCIA, which could predict the
      outcome of renal function in these patients.

PMID- 25780625
TI  - The use of tissue plasminogen activator as continuous infusion into an
      arteriovenous hemodialysis access in the hemodialysis unit: a case series.
AB  - BACKGROUND: Thrombolytics such as tissue plasminogen activator are often used by
      interventional radiologists in the radiology suite to salvage thrombosed
      hemodialysis arteriovenous fistulae. Thrombolytics are also commonly used in
      dialysis facilities as a dialysis catheter lock solution or as an infusion into a
      dialysis catheter when dysfunctional. However, the use of tissue plasminogen
      activator as a continuous infusion into an arteriovenous fistula in the dialysis
      facility to treat clot burden is not commonly done. OBJECTIVE: The aim of our
      case series is to demonstrate the successful use of tissue plasminogen activator
      to decrease clot burden in an arteriovenous fistula in the dialysis unit. DESIGN:
      Observational case series. SETTING: An outpatient dialysis facility in a tertiary
      care hospital. PATIENTS: Three non- consecutive patients were diagnosed with an
      acute thrombosed arteriovenous fistula either on physical exam or by imaging.
      MEASUREMENTS: A thrombosed fistula as well as successful resolution of clot was
      illustrated by either physical exam, fistulogram or ultrasound. A functioning
      fistula demonstrated successful continuation of dialysis and adequate access flow
      measurements in follow up. METHOD: This is a case series that describes the
      technique of using an infusion of tissue plasminogen activator into an
      arteriovenous fistula on the dialysis unit by vascular access nurses to treat or
      diminish clot burden. RESULTS: We have described three separate cases where
      treatments with tissue plasminogen activator infusions on the dialysis unit
      resulted in objective evidence of decrease in clot burden on ultrasound or
      fistulogram. LIMITATIONS: The small numbers of our case series requires that the
      results need to be verified in a larger study. Inclusion and exclusion criteria
      need to be defined before widespread application of this technique. CONCLUSIONS:
      To our knowledge this small case series is the first to describe the procedure
      whereby low dose tissue plasminogen activator is directly infused into the
      fistula by the vascular access nurse in the dialysis unit during dialysis and not
      in the interventional suite. This provides additional information to the existing
      literature that there is an alternative option for dialysis units to diminish
      clot burden until a more permanent solution is established through angioplasty.

PMID- 25780626
TI  - Validating a scoring tool to predict acute kidney injury (AKI) following cardiac
      surgery.
AB  - BACKGROUND: Acute kidney injury (AKI) after cardiac surgery is associated with an
      increased risk of mortality. Preoperative risk scores can identify patients at
      risk for AKI and facilitate preventive strategies. Currently, validated risk
      scores are used to predict AKI requiring dialysis (AKI-D); less is known about
      whether these tools predict less severe forms of AKI. OBJECTIVE: To evaluate the
      Cleveland Clinic scoring tool in predicting both AKI-D and less severe stages of
      AKI in patients after cardiac surgery in a Canadian tertiary care center. DESIGN:
      Retrospective case-control study. SETTING: Regina Qu'Appelle Health Region (RQHR)
      from 2007 to 2011. PATIENTS: Patients who underwent cardiac surgery and developed
      postoperative kidney injury (n = 2316). MEASUREMENTS: Data on risk factors for
      AKI and outcomes of cardiac surgery were collected from a retrospective chart
      review. METHODS: The primary outcome was AKI, defined as Stage 1 (increase in
      serum creatinine 1.5-1.9 X baseline within 5 days), Stage 2 (increase 2.0-2.9 X
      baseline), or Stage 3 (increase 3.0 X baseline or more OR initiation of dialysis
      during hospital stay). We assessed the performance of a modified version of the
      Cleveland Clinic tool using receiver operating curve analyses. RESULTS: The
      incidence of AKI was 6.1% (Stage 1), 2.6% (Stage 2), and 5.8% (Stage 3). The area
      under the curve (AUC) for the Cleveland score was 0.61 (95% CI: 0.56 to 0.65; p <
      0.001) for Stage 1, 0.61 (95% CI: 0.54 to 0.68; p < 0.01) for Stage 2, and 0.78
      (95% CI: 0.74 to 0.82; p < 0.001) for Stage 3. Greater level of risk on the
      Cleveland tool was associated with a higher risk of Stage 3 AKI. LIMITATIONS:
      Lack of prospective validation. CONCLUSIONS: The modified Cleveland Clinic tool
      was valid in identifying patients with severe stages of AKI but did not have
      strong discrimination for early AKI stages.

PMID- 25780628
TI  - Development of a hemodialysis safety checklist using a structured panel process.
AB  - BACKGROUND: The World Health Organization created a Surgical Safety Checklist
      with a pause or "time out" to help reduce preventable adverse events and improve
      communication. A similar tool might improve patient safety and reduce treatment
      associated morbidity in the hemodialysis unit. OBJECTIVE: To develop a
      Hemodialysis Safety Checklist (Hemo Pause) for daily use by nurses and patients.
      DESIGN: A modified Delphi consensus technique based on the RAND method was used
      to evaluate and revise the checklist. SETTING: University-affiliated in-center
      hemodialysis unit. PARTICIPANTS: A multidisciplinary team of physicians, nurses,
      and administrators developed the initial version of the Hemo Pause Checklist. The
      evaluation team consisted of 20 registered hemodialysis nurses. MEASUREMENTS: The
      top 5 hemodialysis safety measures according to hemodialysis nurses. A 75%
      agreement threshold was required for consensus. METHODS: The structured panel
      process was iterative, consisting of a literature review to identify safety
      parameters, individual rating of each parameter by the panel of hemodialysis
      nurses, an in-person consensus meeting wherein the panel refined the parameters,
      and a final anonymous survey that assessed panel consensus. RESULTS: The
      literature review produced 31 patient safety parameters. Individual review by
      panelists reduced the list to 25 parameters, followed by further reduction to 19
      at the in-person consensus meeting. The final round of scoring yielded the
      following top 5 safety measures: 1) confirmation of patient identity, 2)
      measurement of pre-dialysis weight, 3) recognition and transcription of new
      medical orders, 4) confirmation of dialysate composition based on prescription,
      and 5) measurement of pre-dialysis blood pressure. Revision using human factors
      principles incorporated the 19 patient safety parameters with greater than or
      equal to 75% consensus into a final checklist of 17-items. LIMITATIONS: The
      literature review was not systematic. This was a single-center study, and the
      panel lacked patient and family representation. CONCLUSIONS: A novel 17-item
      Hemodialysis Safety Checklist (Hemo Pause) for use by nurses and patients has
      been developed to standardize the hemodialysis procedure. Further quality
      improvement efforts are underway to explore the feasibility of using this
      checklist to reduce adverse events and strengthen the safety culture in the
      hemodialysis unit.

PMID- 25780629
TI  - Effect of Egg White Combined with Chalcanthite on Lipopolysaccharide induced
      Inflammatory Cytokine Expression in RAW 264.7 cells.
AB  - AIM: Historically, mineral compound herbal medicines have long been used in
      treatments of immune-related diseases in Korea, China and other Asian countries.
      In this study, we investigated the anti-inflammatory effect of egg white combined
      with chalcanthite (IS4) on lipopolysaccharide (LPS)-stimulated RAW 264.7 cells.
      METHODS: RAW 264.7 cells cultured with LPS and various concentrations of IS4 were
      analyzed to determine the production of pro-inflammatory cytokines and mediators
      by using enzyme-linked immune sorbent assays (ELISAs). RESULTS: IS4 concentration
      inhibited the production of interleukin-1beta (IL-1 beta), interleukin-6 (IL-6),
      and granulocyte -macrophage colony-stimulating factor (GM-CSF) induced by LPS.
      IS4 at high concentrations (25 and 50?/ml) inhibited, in concentration-dependent
      manner, the expression of tumor necrosis factor-alpha (TNF- alpha) stimulated by
      LPS. CONCLUSION: IS4 has shown an anti-inflammatory effect in RAW 264.7 cells.

PMID- 25780630
TI  - Effects of atractylodis rhizoma pharmacopuncture on an acute gastric mucosal
      lesion induced by compound 48/80 in rats.
AB  - OBJECTIVES: This study was designed to investigate the protective effects of
      Atractylodis Rhizoma pharmacopuncture (ARP) against acute gastric mucosal lesions
      induced by compound 48/80 in rats. METHODS: The ARP was injected in Joksamni
      (ST36) and Jungwan (CV12) 1 hr before treatment with compound 48/80. The animals
      were sacrificed under anesthesia 3 hrs after treatment with compound 48/80. The
      stomachs were removed, and the amounts of gastric adherent mucus, gastric mucosal
      hexosamine, thiobarbituric acid reactive substances (TBARS), xanthine oxidase
      (XO), and superoxide dismutase (SOD) were measured. Also, histological
      examination were performed. RESULTS: Gastric adherent mucus, gastric mucosal
      hexosamine and histological defects of gastric mucosa declined significantly
      after ARP treatment. Changes in gastric mucosal TBARS were also reduced by ARP
      treatment, but this result was not statistically significant. ARP treatment did
      not change the XO and the SOD activities. CONCLUSIONS: ARP showed protective
      effects for acute gastric mucosal lesions induced by compound 48/80 in rats.
      These results suggest that ARP may have protective effects for gastritis.

PMID- 25780631
TI  - Identification and Expression Analysis of Chloroplast p-psbB Gene Differentially
      Expressed in Wild Ginseng.
AB  - Panax ginseng is a well-known herbal medicine in traditional Asian medicine.
      Although wild ginseng is widely accepted to be more active than cultivated
      ginseng in chemoprevention, little has actually been reported on the difference
      between wild ginseng and cultivated ginseng. Using suppressive subtraction
      hybridization, we cloned the p-psbB gene as a candidate target gene for a wild
      ginseng-specific gene. Here, we report that one of the clones isolated in this
      screen was the chloroplast p-psbB gene, a chlorophyll a-binding inner antenna
      protein in the photosystem II complex, located in the lipid matrix of the
      thylakoid membrane. Real-time results showed that the expression of the p-psbB
      gene was significantly up-regulated in wild ginseng as compared to cultivated
      ginseng. Thus, the p-psbB gene may be one of the important markers of wild
      ginseng. 

PMID- 25780632
TI  - Testing of the Safety and the Effectiveness of Using SamjeongPharmacopuncture
      Solution as Eye drops.
AB  - OBJECTIVE: This experimental study was designed to investigate the safety and the
      effectiveness of Samjeong pharmacopuncture solution (SPS) manufactured by using a
      the lowtemperature extract on process. METHODS: To identify the safety and the
      effectiveness of using SPS as eye drops, we performed applied eye irritation
      tests on rabbits and antibacterial tests for Staphylococcus aureus,
      Staphylococcus epidermidis, Pseudomonas aeruginosa, Aspergillus niger, Fusarium
      oxysporum, and Candida albicans. The eye irritation test was performed according
      to the toxicity testing regulation of the Korea Food & Drug Administration (2009.
      8. 24, KFDA 2009-116). After SPS had been applied on the left eye of the rabbits,
      eye irritation in the cornea, iris and conjunctiva was observed on the 1st, 2nd,
      3rd, 4th & 7th day. After SPS had been dropped on bacterial species that cause
      keratitis, the minimum inhibition concentration and the size of the inhibition
      zone were measured. The anti-bacterial potency was also measured by taking the
      size of inhibition zone. RESULTS: After SPS had been administered on the left eye
      of the rabbits, none of nine rabbits were found to show abnormal signs or weight
      changes. After SPS had been administered on the left eye of the rabbits, no eye
      irritation in the cornea, iris and conjunctiva was observed on the 1st, 2nd, 3rd,
      4th & 7th day. No specific response was detected in MIC for bacterial species
      Staphylococcus aureus, Staphylococcus epidermidis, Pseudomonas aeruginosa,
      Aspergillus niger, Fusarium oxysporum, and Candida albicans after SPS had been
      applied. CONCLUSIONS: This study suggests that SPS is a non-toxic and non
      irritant medicine that does not cause any of eye irritation in rabbits, but it
      has no antibacterial effects on bacterial species that are well known to cause
      keratitis. These results suggest that more research is required on extracts from
      herbal medicines for treating keratitis.

PMID- 25780633
TI  - Modulatory Effects of Chrysanyhemi Flos Pharmacopuncture on Nitric-oxide (NO)
      Production in Murin Macrophagy Cells.
AB  - OBJECTIVES: Much evidence exists that herbs have effective immunomodulatory
      activities. Chrysanthemi Flos (CF) is effective in clearing heat, reducing
      inflammation, dropping blood pressure and treating headache and is used as a
      pharmaceutical raw material for an immune enhancer. The purpose of this study was
      to investigate the modulatory effect of Chrysanthemi Flos pharmacopuncture on
      nitric-oxide (NO) production in activating macrophages. METHODS: After a murine
      macrophage cell line, RAW 264.7, was cultured in the presence of
      lipopolysaccharide (LPS), immune-modulating abilities of CF were evaluated by
      using NO, interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha)
      production and phagocytic activity of macrophages. RESULTS: CF enhanced the
      activities of macrophages by increasing the phagocytic activity and decreasing NO
      production. Especially, both LPS and CF, 200 ?/ml, treatment could significantly
      reduce the NO production, but did not change the production of IL-6 and TNF
      alpha. CONCLUSION: The results of this study indicate that CF may be of
      immunomodulatory value, especially for adverse diseases due to increased NO
      production. It may have potential for use as immunoenhancing pharmacopuncture.

PMID- 25780634
TI  - Influence of prescribed herbal and Western medicine on patients with abnormal
      liver function tests: a retrospective quasi-experimental study.
AB  - OBJECTIVES: The aim of this study was to investigate the safety and the efficacy
      of Korean herbal, western and combination medicine use in patients with abnormal
      liver function tests. METHODS: We investigated nerve disease patients with
      abnormal liver function tests who were treated with Korean herbal, western and
      combination medicine at Dong-Eui University Oriental Hospital from January 2011
      to August 2011. We compared aspartic aminotransferase (AST), alanine
      aminotransferase (ALT), alkaline phosphatase (ALP) and total bilirubin (T-bil)
      levels before and after taking medicine and excluded patients who had liver
      related disease when admitted. RESULTS: AST and ALT were decreased significantly
      in patients who had taken herbal, western medicine. AST, ALT and ALP were
      decreased significantly in patients who had taken combination medicine. Compare
      to herbal medicine, AST, ALT and ALP were decreased significantly in patients who
      had taken western medicine, and ALT and ALP were decreased significantly in
      patients who had taken combination medicine. There were no significant
      differences between western and combination medicine. CONCLUSIONS: This study
      suggests that prescribed Korean herbal medicine, at least, does not injure liver
      function for patients', moreover, it was shown to be effective in patients with
      abnormal liver function tests.

PMID- 25780635
TI  - Effect of lithospermi radix on contact dermatitis induced by dinitrofluorobenzene
      in mice.
AB  - OBJECTIVE: The root of Lithospermum erythrorhizon Sieb. et Zucc. (Lithospermi
      Radix, LR) is a kind of heat clearing and blood cooling medicinal herbs. It can
      clear away heat and cool the blood, reduce toxins and disperse maculae. LR has
      long been used as efficacious therapy for inflammation, burns, frostbite and skin
      diseases such as eczema and psoriasis. METHODS: In the present study, we
      investigate anti-allergic and anti-inflammatory effects of LR by using the 1
      fluoro-2, 4- dinitrofluorobenzene (DNFB)-induced contact dermatitis mouse model.
      RESULTS: Topical application of 10 mg/mL of LR effectively inhibited skin lesions
      induced by repeated paintings with DNFB. Topical application of LR also inhibited
      hyperplasia, edema, spongiosis and infiltrations of mononuclear cells. In
      addition, production levels of total immunoglobulin and IgG1 in serum were
      decreased by using LR in vivo. CONCLUSION: These data suggest that LR acts as an
      antiinflammatory agent, improving skin lesions in CD mice.

PMID- 25780636
TI  - An Experimental Study of the Anti-oxidant and the Anti-inflammatory Effects of
      Alum and Burnt Alum.
AB  - OBJECTIVES: The purpose of this study was to compare the antioxidant and anti
      inflammatory effects of Alum (AL) and Burnt Alum (BAL), which are commonly used
      as external ointments. METHODS: Extracts of AL and BAL were classified into three
      groups: 20, 50, and 100 ?/?. The cytotoxicity was measured by using MTT assays in
      human keratinocyte cell line (HaCaT). The anti-oxidant effect was measured by
      using the DPPH (1, 1-diphenyl-2-picryl-hydrazyl-hydrate) radical scavenger. The
      anti-inflammatory effect was measured by using the inhibitory efficacy for the
      amount of nitric-oxide (NO) produced in mouse macrophage cell line (RAW 264.7).
      RESULTS: BAL showed a higher level of cytotoxicity than AL. The AL groups showed
      a concentration-dependent scavenging effect on DPPH radicals, but no significant
      relevance was found. The BAL groups showed a concentration-dependent scavenging
      effect on DPPH radicals. The scavenging effects of the BAL groups were almost
      insignificant, but the values for the 20, 50, and 100 ?/? trials were different.
      The BAL groups showed significant concentration-dependent inhibitory effects on
      NO production, but the AL groups did not. CONCLUSIONS: AL showed an anti-oxidant
      effect more efficiently than BAL did, which demonstrated a superior anti
      inflammatory effect. Therefore, for external usage, AL must be distinguished from
      BAL.

PMID- 25780637
TI  - Effects of sophorae radix on human gastric and colorectal adenocarcinoma cells:
      sophorae radix and cancer cells.
AB  - The purpose of this study was to investigate the anti-cancer effects of Sophorae
      Radix (SR) and doxorubicin (DOX) in human gastric and colorectal adenocarcinoma
      cells. We used the human gastric and colorectal adenocarcinoma cell lines (MKN-45
      and WIDR cells, respectively). We examined cell death by using the MTT(3-[4, 5
      dimethylthiazol-2-yl]-2, 5- diphenyltetrazolium bromide) assay and the caspase 3
      assay with SR. To examine the inhibitory effects of SR, we performed a cell cycle
      (sub G1) analysis for the MKN-45 and WIDR cells after three days with SR. The
      reversibility of SR was examined for one-day to five-day treatments with SR. SR
      inhibited the growth of MKN-45 and WIDR cells in a dosedependent manner. Also, we
      showed that SR induced apoptosis in MKN-45 and WIDR cells by using the MTT assay,
      the caspase 3 assay and the sub-G1 analysis. SR combined with DOX markedly
      inhibited the growth of MKN-45 and WIDR cells compared to SR or DOX alone. After
      3 days of treating MKN-45 and WIDR cells with SR, the fraction of cells in the
      sub-G1 phase was much higher than that of the control group. Our findings provide
      insights into unraveling the effects of SR on human gastric and colorectal
      adenocarcinoma cells and into developing therapeutic agents for use against
      gastric and colorectal adenocarcinomas. 

PMID- 25780638
TI  - Identification and Analysis of the Chloroplast rpoC1 Gene Differentially
      Expressed in Wild Ginseng.
AB  - Panax ginseng is a well-known herbal medicine in traditional Asian medicine, and
      wild ginseng is widely accepted to be more active than cultivated ginseng in
      chemoprevention. However, little has actually been reported on the difference
      between wild ginseng and cultivated ginseng. Thus, to identify and analyze those
      differences, we used suppressive subtraction hybridization (SSH) sequences with
      microarrays, realtime polymerase chain reaction (PCR), and reverse transcription
      PCRs (RT-PCRs). One of the clones isolated in this research was the chloroplast
      rpoC1 gene, a beta subunit of RNA polymerase. Real-time RT-PCR results showed
      that the expression of the rpoC1 gene was significantly upregulated in wild
      ginseng as compared to cultivated ginseng, so, we conclude that the rpoC1 gene
      may be one of the important markers of wild ginseng. 

PMID- 25780639
TI  - Compositional Differences of Ojeok-san (Wuji-san) Decoctions Using Pressurized or
      Non-pressurized Methods for Variable Extraction Times.
AB  - This study compared Ojeok-san (Wuji-san in Chinese) decoctions produced using
      different extraction methods for variable times. Decoctions were extracted in
      pressurized or non-pressurized conditions for 60, 120, and 180 mins. We
      investigated the Ojeok-san extract yield, the total soluble solid content, the
      hydrogen ion concentration (pH), and the reference compound content. The extract
      yield and the total soluble solid content were higher in decoctions produced by
      non-pressurized extraction; both were proportional to the extraction time. The pH
      tended to decrease as the extraction time was increased in decoctions produced
      using both methods. After 60 and 180 mins, the levels of albiflorin,
      paeoniflorin, nodakenin, naringin, and neohesperidin were significantly higher in
      decoctions extracted using the non-pressurized method compared with those
      extracted using the pressurized method. After 120 mins, only cinnamaldehyde was
      extracted in a greater amount in pressurized decoctions compared with non
      pressurized decoctions. The levels of paeoniflorin, ferulic acid, nodakenin,
      naringin, hesperidin, neohesperidin, and glycyrrhizin increased with time in non
      pressurized decoctions. This study showed that the use of pressurized and non
      pressurized extraction methods for different times affected the composition of
      Ojeoksan (Wuji-san) decoctions. 

PMID- 25780640
TI  - A Case Series of Survival Outcomes in Patients with Advanced-stage IIIb/IV Non
      small-cell Lung Cancer Treated with HangAm-Plus.
AB  - BACKGROUND AND OBJECTIVES: Non-small-cell lung cancer (NSCLC) represents
      approximately 80% of all lung cancers. Unfortunately, at their time of diagnosis,
      most patients have advanced to unresectable disease with a very poor prognosis.
      The oriental herbal medicine HangAm-Plus(HAP) has been developed for antitumor
      purposes, and several previous studies have reported its therapeutic effects. In
      this study, the efficacy of HAP was evaluated as a third-line treatment for
      advanced-stage IIIb/IV NSCLC. METHODS: The study involved six patients treated at
      the East- West Cancer Center (EWCC) from April 2010 to October 2011. Inoperable
      advanced-stage IIIb/IV NSCLC patients received 3,000 or 6,000 mg of HAP on a
      daily basis over a 12-week period. Computed tomography (CT) scans were obtained
      from the patients at the time of the initial administration and after 12 weeks of
      treatment. We observed and analyzed the patients overall survival (OS) and
      progression-free survival (PFS). RESULTS: Of the six patients, three expired
      during the study, and the three remaining patients were alive as of October 31,
      2011. The OS ranged from 234 to 512 days, with a median survival of 397 days and
      a one-year survival rate of 66.7%. In the 12-week-interval chest CT assessment,
      three patients showed stable disease (SD), and the other three showed progressive
      disease (PD). The PFS of patients ranged from 88 to 512 days, the median PFS
      being 96 days. Longer OS and PFS were correlated with SD. Although not directly
      comparable, the OS and the PFS of this study were greater than those of the
      docetaxel or the best supportive care group in other studies. CONCLUSION: HAP may
      prolong the OS and the PFS of inoperable stage IIIb/IV NSCLC patients without
      significant adverse effects. In the future, more controlled clinical trials with
      larger samples from multi-centers should be conducted to evaluate the efficacy
      and the safety of HAP.

PMID- 25780641
TI  - Acupuncture and spontaneous regression of a radiculopathic cervical herniated
      disc.
AB  - The spontaneous regression of herniated cervical discs is not a well-established
      phenomenon. However, we encountered a case of a spontaneous regression of a
      severe radiculopathic herniated cervical disc that was treated with acupuncture,
      pharmacopuncture, and herb medicine. The symptoms were improved within 12 months
      of treatment. Magnetic resonance imaging (MRI) conducted at that time revealed
      marked regression of the herniated disc. This case provides an additional example
      of spontaneous regression of a herniated cervical disc documented by MRI
      following non-surgical treatment. 

PMID- 25780642
TI  - A literature study on usage of and satisfaction levels with combined treatment
      including oriental and Western medicine.
AB  - OBJECTIVE: This study aimed to summarize and analyze the usage of and the
      satisfaction levels with combined treatment including Oriental and Western
      medicine. METHODS: We searched studies on the usage of and the satisfaction
      levels with combined treatment including Oriental and Western medicine over the
      past 10 yrs (2001-2011) from 3 Korean databases (National Assembly Library,
      Research Information Service System, and National Discovery for Science Leaders).
      The reviewers also conducted a summarizing analysis by sampling the literature
      according to the type of study, study period, region, study subjects, sample
      size, type of sampling, research method, data analysis, study instruments, main
      results, etc. RESULTS: When the main results of six studies on combined treatment
      usage and satisfaction levels were considered together, the most important
      decisive factor in determining the usage of combined treatment was the illness of
      the patient, followed by the patient's occupation, sex, age, education, marital
      status, religion, treatment cost, and treatment results. In addition, the most
      important factor that determined satisfaction levels with combined treatment was
      age, followed by education, religion, income, health status, treatment
      procedures, staff attitude, and cleanliness. CONCLUSIONS: Elderly patients with
      musculoskeletal, cerebrovascular, and circulatory system illnesses are more
      likely to prefer combined treatment over independent Oriental or Western
      treatment and are more likely to request specialized, adjusted medical care.

PMID- 25780643
TI  - Stimulative Effects of Hominis Placental Pharmacopuncture Solution Combined with
      Zinc-oxide Nanoparticles on RAW 264.7 Cells: ZnO HPPS more easily stimulates RAW
      264.7 cells.
AB  - OBJECTIVES: The purpose of this study is to examine whether Hominis Placental
      pharmacopuncture solution (HPPS) combined with zinc-oxide nanoparticles (ZnO NP)
      activates RAW 264.7 cells. METHODS: We soaked ZnO nanoparticles in the Hominis
      Placenta pharmacopuncture solution, thereby making a combined form (ZnO NP HPPS).
      The effect of ZnO NP HPPS on the intracellular reactive oxygen species (ROS)
      production was measured by 2', 7'-dichlorofluorescin diacetate (DCFH-DA) assay.
      The effect of ZnO NP HPPS on NF-kappa B was measured by using a luciferase assay.
      The effect of ZnO NP HPPS on the cytokine expression was assessed by semi
      quantitative reverse transcriptase polymerase chain reaction (RT-PCR). The
      cellular uptake of ZnO NP HPPS was measured by using a flow cytometric analysis,
      and cellular structural alterations were analyzed by using transmission electron
      microscopy (TEM). RESULTS: Neither the HPPS nor the ZnO NPs induced intracellular
      ROS production in RAW 264.7 cells. Neither of the materials activated NF-kappa B
      or it's dependent genes, such as TNF-alpha, IL-1, and MCP-1. However, ZnO NP
      HPPS, the combined form of ZnO NPs and HPPS, did induce the intracellular ROS
      production, as well as prominently activating NF-kappa B and it's dependent
      genes. Also, compared to ZnO NPs, it effectively increased the uptake by RAW
      264.7 cells. In addition, cellular structural alterations were observed in groups
      treated with ZnO NP HPPS. CONCLUSIONS: Neither ZnO NP nor HPPS activated RAW
      264.7 cells, which is likely due to a low cellular uptake. The ZnO NP HPPS,
      however, significantly activated NF-kappa B and up-regulated its dependent genes
      such as TNF-alpha, IL-1, and MCP-1. ZnO NP HPPS was also more easily taken into
      the RAW 264.7 cells than either ZnO NP or HPPS.

PMID- 25780644
TI  - Galectin-3-independent Down-regulation of GABABR1 due to Treatment with Korean
      Herbal Extract HAD-B Reduces Proliferation of Human Colon Cancer Cells.
AB  - OBJECTIVES: Many efforts have shown multi-oncologic roles of galectin-3 for cell
      proliferation, angiogenesis, and apoptosis. However, the mechanisms by which
      galectin-3 is involved in cell proliferation are not yet fully understood,
      especially in human colon cancer cells. METHODS: To cluster genes showing
      positively or negatively correlated expression with galectin-3, we employed human
      colon cancer cell lines, SNU-61, SNU-81, SNU-769B, SNU-C4 and SNU-C5 in high
      throughput gene expression profiling. Gene and protein expression levels were
      determined by using real-time quantitative polymerase chain reaction (PCR) and
      western blot analysis, respectively. The proliferation rate of human colon cancer
      cells was measured by using a 3-(4, 5- dimethylthiazol-2-yl)-2, 5
      diphenyltetrazolium bromide (MTT) assay. RESULTS: Expression of gamma
      aminobutyric acid B receptor 1 (GABABR1) showed a positive correlation with
      galectin-3 at both the transcriptional and the translational levels.
      Downregulation of galectin-3 decreased not only GABABR1 expression but also the
      proliferation rate of human colon cancer cells. However, Korean herbal extract,
      HangAmDan-B (HAD-B), decreased expression of GABABR1 without any expressional
      change of galectin-3, and offset gamma-aminobutyric acid (GABA)-enhanced human
      colon cancer cell proliferation. CONCLUSIONS: Our present study confirmed that
      GABABR1 expression was regulated by galectin-3. HAD-B induced galectin-3
      independent down-regulation of GABABR1, which resulted in a decreased
      proliferation of human colon cancer cells. The therapeutic effect of HAD-B for
      the treatment of human colon cancer needs to be further validated.

PMID- 25780645
TI  - Involvement of Transient Receptor Potential Melastatin 7 Channels in Sophorae
      Radix-induced Apoptosis in Cancer Cells: Sophorae Radix and TRPM7.
AB  - Sophorae Radix (SR) plays a role in a number of physiologic and pharmacologic
      functions in many organs. OBJECTIVE: The aim of this study was to clarify the
      potential role for transient receptor potential melastatin 7 (TRPM7) channels in
      SR-inhibited growth and survival of AGS and MCF-7 cells, the most common human
      gastric and breast adenocarcinoma cell lines. METHODS: The AGS and the MCF-7
      cells were treated with varying concentrations of SR. Analyses of the caspase-3
      and - 9 activity, the mitochondrial depolarization and the poly (ADPribose)
      polymerase (PARP) cleavage were conducted to determine if AGS and MCF-7 cell
      death occured by apoptosis. TRPM7 channel blockers (Gd(3+) or 2-APB) and small
      interfering RNA (siRNA) were used in this study to confirm the role of TRPM7
      channels. Furthermore, TRPM7 channels were overexpressed in human embryonic
      kidney (HEK) 293 cells to identify the role of TRPM7 channels in AGS and MCF-7
      cell growth and survival. RESULTS: The addition of SR to a culture medium
      inhibited AGS and MCF-7 cell growth and survival. Experimental results showed
      that the caspase-3 and -9 activity, the mitochondrial depolarization, and the
      degree of PARP cleavage was increased. TRPM7 channel blockade, either by Gd(3+)
      or 2-APB or by suppressing TRPM7 expression with small interfering RNA, blocked
      the SR-induced inhibition of cell growth and survival. Furthermore, TRPM7 channel
      overexpression in HEK 293 cells exacerbated SR-induced cell death. CONCLUSIONS:
      These findings indicate that SR inhibits the growth and survival of gastric and
      breast cancer cells due to a blockade of the TRPM7 channel activity. Therefore,
      TRPM7 channels may play an important role in the survival of patients with
      gastric and breast cancer.

PMID- 25780646
TI  - Clinical Review of the Effects of Chukyu (spinehealing) Pharmacopuncture in the
      Treatment of Lumbago and Skelalgia Patients.
AB  - OBJECTIVE: The purpose of this study is to report the effects of Chukyu (spine
      healing) pharmacopuncture treatment in patients with lumbago and skelalgia.
      METHODS: This clinical study included 45 patients who were treated for lumbago
      and skelalgia at the Department of Acupuncture and Moxibusition, Dong-Eui
      University College of Oriental Medicine, from July 5, 2011, to January 31, 2012.
      Subjects were randomly divided into two groups: Chukyu (spinehealing)-
      pharmacopuncture-treated group (experimental group, n = 23) and normal saline
      pharmacopuncture-treated group (control group, n = 22). Patients in the
      experimental group were treated with acupuncture and Chukyu (spine-healing)
      pharmacopuncture while those in the control group were treated with acupuncture
      and normal saline pharmacopuncture. To estimate the efficacy of controlling pain,
      we checked the visual analog scale [VAS], and to estimate the improvement of the
      symptoms, we evaluated by pain rating scale [PRS] and the Oswestry low-back pain
      disability index [ODI]. RESULTS: A comparison of the experimental and the control
      groups showed more significant improvements in the VAS, PRS, and ODI for the
      experimental group than for the control group. CONCLUSIONS: Chukyu (spine
      healing) pharmacopuncture can be used for effective treatment in patients with
      lumbago and skelalgia.

PMID- 25780647
TI  - Correlation between the Constitution of Sasang and Sexual Difference in the
      Hypersensitive Reaction of Sweet Bee Venom.
AB  - OBJECTIVES: The aim of this study is to investigate the correlation between the
      constitution of Sasang and the bee venom hypersensitive reaction, as well as the
      hypersensitive reaction occurrence ratio between males and females, for patients
      treated with sweet bee venom (SBV) and who had undergone an examination of the
      constitution of the Sasang. METHODS: All 81 patients enrolled in the study were
      treated with SBV and underwent an examination of the constitution of Sasang from
      January 2010 to July 2012. We divided them into two groups for the hypersensitive
      reaction and no response and compared the distributions of the Sasang
      constitution types for the two groups as well as the hypersensitive reaction
      occurrence ratio between males and females. RESULTS: No significant differences
      were found between the hypersensitive-reaction group and the no-response group
      (p= 0.390), but the hypersensitive-reaction occurrence ratio was statistically
      higher in females than in males (p= 0.001). CONCLUSIONS: Hypersensitive reactions
      do not seem to be related to the Sasang-constitution types, but the possibility
      of hypersensitive reactions among females seems to be higher than it is among
      males.

PMID- 25780648
TI  - Study of Single-dose Toxicity of Aconitum Kusnezoffii Reichb. Pharmacopuncture in
      Rats.
AB  - OBJECTIVE: This study was performed to analyze the singledose toxicity of
      Aconitum kusnezoffii Reichb. pharmacopuncture (AKRP). METHODS: All experiments
      were conducted at the Korea Testing & Research Institute (KTRI), an institute
      authorized to perform non-clinical studies, under the regulations of Good
      Laboratory Practice (GLP). Twenty (20) Sprague-Dawley rats were chosen for the
      pilot study. The animals were divided into four groups of five animals per group:
      group 1 (G1) being the control group with each animal receiving an injection of
      0.3 ml of saline and groups 2, 3, and 4 (G2, G3, and G4) being the experimental
      groups with each animal receiving an injection of 0.1, 0.2 or 0.3 ml of AKRP,
      respectively. This study was conducted with the approval of the Institutional
      Animal Ethics Committee. RESULTS: No deaths occurred in any of the 4 groups, and
      the LD50 of AKRP administered via IV was higher than 1.77 ml/kg. Some changes in
      the weights of the male rates were observed between the control group and the
      experimental groups, but no significant differences were noted in the weights of
      the female rats. To check for abnormalities in organs and tissues, we stained
      representative sections of each specified organ with Hematoxylin & Eosin for
      light microscopic examination. The results showed no significant differences in
      any of the organs or tissues. CONCLUSIONS: The above findings suggest that
      Aconitum kusnezoffii Reichb. pharmacopuncture is a relatively safe treatment.
      Further studies on the subject should be conducted to yield more concrete
      evidence.

PMID- 25780649
TI  - Comparative study on the effects of bee venom pharmacopuncture according to the
      treatment method for knee osteoarthritis.
AB  - OBJECTIVES: The purpose of this study is to compare the effects of bee venom
      pharmacopuncture (BVP) therapy according to the methods used to treat knee
      osteoarthritis (OA): intra-acupoint combined with intra-articular injection,
      intra-acupoint injection, and intra-articular injection. METHODS: A total of 69
      patients were recruited by the Department of Acupuncture & Moxibustion at Dong-
      Eui Oriental University Hospital from February 1 to July 23, 2012. The patients
      were assigned to 3 groups: the first group with intra-acupoint combined with
      intraarticular BVP Injection (the experimental group), the 2nd group with intra
      acupoint BVP injection (control groupI), and the 3rd group with intra-articular
      BVP injection (control groupII). The participants were assigned in the order in
      which they were recruited. Treatments were done twice a week, for a total of 9
      times. The effectiveness was assessed by using the visual analouge scale (VAS)
      and the Korea Western Ontario and McMaster Universities Osteoarthritis Index
      (KWOMAC). RESULTS: All three groups exhibited significant VAS and KWOMAC effects.
      Moreover, the 4 week follow-up after the final treatment showed a persistence of
      BVP effects. However, when the groups were compared, no statistically significant
      differences in VAS and KWOMAC were noted, but when improvement was considered,
      the results showed that intra-articular injection was more effective than intra
      acupoint injection. Especially, intra-acupoint combined with intra-articular
      injection was the most effective among the three treatments. CONCLUSIONS:
      Combining intra-acupoint with intraarticular injection, depending on the
      patient's symptoms, may produce better results when conservatively treating knee
      OA.

PMID- 25780650
TI  - Clinical research of the efficacy and the safety of dioscoreae rhizoma (sanyak)
      pharmacopuncture therapy for peripheral facial paralysis patients.
AB  - OBJECTIVES: The aim of this study is to evaluate the efficacy and the safety of
      Sanyak pharmacopuncture therapy for the treatment of peripheral facial paralysis
      patients. METHODS: This study was a retrospective investigation of a total of 70
      patients who were inpatients of the Oriental Hospital of Daejeon University
      between January 1, 2011, and May 31, 2012, and who were diagnosed as having
      peripheral facial paralysis by physical examination, the patients received three
      different interventions. Eleven (11) patients were treated with acupuncture and
      alcohol Dioscorea rhizoma pharmacopuncture (ADG), 25 patients with acupuncture
      and distillation Dioscorea rhizoma pharmacopuncture (DDG), and 34 patients with
      acupuncture and non-Dioscorea rhizoma pharmacopuncture (NDG). The resulting data
      were analyzed. RESULTS: The changed H-B grades indicated significant improvements
      in all three groups, and the ADG and the DDG groups showed significant results
      after two weeks of treatment when compared to the NDG group. The changed y-Scores
      indicated significant improvements in all three groups, and the ADG group showed
      significant results after 10 and 15 days of treatment when compared to the NDG
      group. Dioscorea rhizoma pharmacopuncture may be safe for the human body because
      in most cases, the only abnormal finding was the pain could by the application of
      pharmacopuncture. CONCLUSIONS: The results of this study suggest that Oriental
      medical treatment with dioscoreae Rhizoma (Sanyak) pharmacopuncture complex
      therapy may be effective and safe in patient with peripheral facial paralysis.

PMID- 25780651
TI  - Effect of Scolopendrid Calculus Bovis-Fel Uris- Moschus Bee Venom and Sweet Bee
      Venom on Regional Cerebral Blood Flow after Pharmacopuncture to GV16 Pungbu and
      GB20 Pungji in Rat.
AB  - OBJECTIVES: This study was designed to investigate the effect of four
      pharmacopuncture drugs (scolopendrid, Calculus Bovis-Fel Uris-Moschus (BUM), bee
      venom 25%, and sweet bee venom 10%) on the cerebral hemodynamics, including
      changes in the regional cerebral blood flow (rCBF) and in the mean arterial blood
      pressure (MABP). METHODS: The changes in the rCBF and the MABP were determined by
      using a laser-Doppler flowmeter and a pressure transducer, respectively. RESULTS:
      Scolopendrid (0.3 ml, 1 ml/kg) caused no significant changes in the rCBF and the
      MABP, whereas BUM (0.3 ml, 1 ml/kg) decreased the rCBF and the MABP, bee venom
      25% (0.3 ml, 1 ml/kg) increased the rCBF and lowered the MABP, and sweet bee
      venom 10% (0.3 ml, 1 ml/kg) increased the rCBF and had no significant effect on
      the MABP. CONCLUSIONS: The rCBF and the MABP were influenced differently by the
      administration of various pharmacopunctures. Further studies are needed to
      elucidate the underlying mechanism.

PMID- 25780652
TI  - Rehmannia Glutinosa Pharmacopuncture Solution Regulates Functional Activation,
      FcepsilonRI Expression, and Signaling Events in Mast Cells.
AB  - OBJECTIVES: Rehmannia glutinosa pharmacopuncture solution (RGPS) was investigated
      to determine both its anti-allergic inflammatory effects on mast cells and its
      detailed mechanism of actions. METHODS: We investigated whether RGPS suppress
      cytokines, enzymes, FcepsilonRI expression and FcepsilonRImediated signaling in
      RBL-2H3 cells stimulated with anti-DNP IgE/DNP-HSA. The suppressive effects of
      RGPS on the levels of cytokines such as IL-1beta, IL-6 and GM-CSF were measured
      using emzyme-linked immunospecific assay (ELISA). The mRNA expression levels of
      cytokines, enzymes (HDC2, COX-1, COX-2 and 5LO) and FcepsilonRI
      alphabetagammasubunits were measured using reverse transcription polymerase chain
      reaction (RTPCR) method. The activation of FcepsilonRI-mediated signaling was
      examined using Western blot analyses. RESULTS: RGPS suppressed production of
      proinflamm-atory cytokines (IL-1beta, IL-6, and GM-CSF) in stimulated RBL-2H3
      cells significantly (p< 0.05). RGPS also suppressed mRNA expression of
      inflammatory enzymes (HDC2, COX-1, COX-2, 5LO). In addition, mRNA expression
      levels of FcepsilonRIalpha, FcepsilonRIbetaand FcepsilonRIgamma were lowered by
      treatment with RGPS. Finally, RGPS prevented phosphrylation of Lyn, Syk, LAT,
      Gab2, PLC gamma1/2, PI3K, Akt, cPLA2 and IkappaBalpha. CONCLUSIONS: RGPS
      effectively suppresses mast cell activations such as degranulation and
      inflammatory response via down-regulation of the FcepsilonRI-mediated signaling
      pathways in IgE/Ag-stimulated mast cells.

PMID- 25780653
TI  - Analytical Research to Determine the effects of the Components of ONGABO on the
      Viability of HepG2 Cancer Cells by Using the Sovereign, Minister, Assistant and
      Courier Principle ().
AB  - OBJECTIVES: This study used the basic principle of Oriental medicine, the
      sovereign, minister, assistant and courier principle () to investigate the
      effects of the component of ONGABO, which is composed of Ginseng Radix (Red
      Ginseng), Angelica Gigantis Radix, Schisandrae Fructus, Cuscuta Semen and
      Curcumae tuber on the viability of HepG2 cells. METHODS: Single and mixed
      extracts of the component of ONGABO were prepared by lypohilizing powder of Red
      Ginseng (6-year root from Kanghwa), Angelica Gigantis Radix, Schisandrae Fructus,
      Cuscuta Semen, Curcumae Tuber (from Omniherb Co., Ltd., Korea) at the laboratory
      of herbal medicine in Woosuk University and were eluted after being macerated
      with 100% ethanol for three days. The cell viability of HepG2 was determined by
      using an absorptiometric analysis with PrestoBlue (Invitrogen) reagent after the
      plate had been incubated for 48 hours. All of the experiments were repeated three
      times to obtain the average value and standard deviation. The statistical
      analysis was done and the correlation factor was obtained by using Microsoft
      Office Excel 2007 and Origin 6.0 software. RESULTS: Although Ginseng Radix (Red
      Ginseng) and Schisandrae Fructus did not enhance the viability of HepG2 cells,
      they were shown to provide protection of those cells. On the other hand, Angelica
      Gigantis Radix decreased the viability of HepG2 cells significantly, Cuscuta
      Semen and Curcumae Tuber had a small or no effect on the viability of HepG2
      cells. CONCLUSIONS: In the sovereign, minister, assistant and courier principle
      (), Ginseng Radix (Red Ginseng) corresponds to the sovereign component because it
      provides cell protection effects, Angelica Gigantis Radix corresponds to minister
      medicinal because it kills cells, Schisandrae Fructus corresponds to the
      assistant medicinal to help red ginseng having cell protect effects. Cuscuta
      Semen and Curcumae Tuber correspond to the courier medicinal having no effect in
      cell viability in HepG2. We hope this study provides motivation for advanced
      research on the sovereign, minister, assistant and courier principle.

PMID- 25780654
TI  - Comparative Analysis of the Bufonis Venenum by Using TLC, HPLC, and LC-MS for
      Different Extraction Methods.
AB  - OBJECTIVES: Toad venom, called Chan-Su, is a traditional Oriental medicine
      secreted from the auricular and the skin glands of the Bufo bufo gargarizanz
      Cantor or B. melanosticus Schneider and has been widely used in China, Korea and
      other parts of Asia for the treatment of pain, heart conditions, and cancer. We
      examined the concentrations of the main chemical constituents within a
      commerciallyavailable toad venom product and compared the levels for different
      extraction methods. METHODS: Toad venom was extracted using either cold or hot
      water, ethanol (EtOH), methanol (MeOH), or ethyl acetate (EtOAc), was
      fractionated using precipitation or reflux, and was then analyzed using thin
      layer chromatography (TLC), high-performance liquid chromatography (HTLC), and
      liquid chroma-tography - mass spectrometry (LC-MS). Individual components were
      identified by comparisons of the retention times, the ultraviolet spectra, and
      mass spectras and differences in chemical constituents for different solvents and
      extraction methods are presented. RESULTS: Components with authentic standards,
      including serotonin and bufodienolides (cinobufagen, bufalin, cinobufalin, and
      resibufogenin), were detected. The water extract of toad venom contained the
      greatest amount of serotonin (75.7 +/- 0.1 mg/g), but very small amounts of
      bufodienolides (3.8 +/- 0.0 mg/g). In contrast, the use of MeOH or EtOH
      extraction solutions resulted in 5-26 times higher concentrations of
      bufodienolides, with only trace amounts of serotonin. The relative and the
      absolute concentrations of the component also varied based on the extraction
      method; i.e., EtOH extracts yielded the greatest total amounts of bufodienolides,
      and EtOAc precipitation had the lowest amounts of bufodienolides. CONCLUSIONS:
      Toad venom consists of serotonin and several bufodienolides, and the choice of
      solvent to extract chemical the constituents is important as a way to enrich the
      purported active components for treating different conditions.

PMID- 25780655
TI  - Idiopathic ninth, tenth, and twelfth cranial nerve palsy with ipsilateral
      headache: a case report.
AB  - OBJECTIVE: This case report is to report the effect of Korean traditional
      treatment for idiopathic ninth, tenth, and twelfth cranial nerve palsy with
      ipsilateral headache. METHODS: The medical history and imaging and laboratory
      test of a 39-year-old man with cranial palsy were tested to identify the cause of
      disease. A 0.2-mL dosage of Hwangyeonhaedoktang pharmacopuncture was administered
      at CV23 and CV17, respectively. Acupuncture was applied at P06, Li05, TE05, and
      G37 on the right side of the body. Zhuapiandutongbang ( ) was administered at 30
      minutes to 1 hour after mealtime three times a day. The symptoms were
      investigated using Visual Analogue Scale (VAS). RESULTS: The results of magnetic
      resonance imaging (MRI), computed tomography (CT), and laboratory tests were
      normal. The medical history showed no trauma, other illnesses, family history of
      diseases, medications, smoking, drinking and so on. All symptoms disappeared at
      the 10th day of treatment. CONCLUSION: Korean traditional treatment such as
      acupuncture, pharmcopuncture, and herbal medicine for the treatment of ninth,
      tenth, and twelfth cranial nerve palsy of unknown origin is suggested to be
      effective even though this conclusion is based on a single.

PMID- 25780656
TI  - Korean Pharmacopuncture Meets Austrian High- Tech Acupuncture - A Short Review
      Article Including a Bibliometric Analysis of Pharmacopuncture over the Last 15
      Years - Pharmacopuncture and Europe.
AB  - OBJECTIVE: Pharmacopuncture, a new therapy in traditional medicine, has attracted
      significant attention since its introduction to the Western world. This short
      review article employs a database analysis to examine the profile of publication
      activity related to pharmacopuncture. METHODS: Three databases were searched:
      PubMed, Embase, and Cochrane. About 300 papers related to the topic
      "pharmacopuncture" were found in these three most-commonly-used databases.
      RESULTS: Fourteen papers are described in detail and are discussed in the context
      of the research performed at the Medical University of Graz, especially by the
      Frank Bahr Research Group "Auriculomedicine and Pharmacopuncture." CONCLUSION:
      High-tech research methods concerning future pharmacopuncture studies are briefly
      discussed.

PMID- 25780657
TI  - Review of tumor dormancy therapy using traditional oriental herbal medicine.
AB  - OBJECTIVE: Standard cancer therapy prolongs survival, but can be detrimental to
      the quality of life, compromise the immune system, and leave residual disease
      that can cause recurrence years or decades in the future. Tumor dormancy therapy
      is a novel therapeutic approach that may improve these shortcomings, promote
      quality of life, and prolong survival. The aim of this study was to analyze
      studies on dormancy therapy, especially studies using traditional Oriental herbal
      medicine, so as to evaluate the efficacy of dormancy therapy with traditional
      oriental herbal medicine. METHODS: We conducted a systematic literature review
      using Scientific and Technical Information Integration Services (NDSL), PubMed,
      and RISS. We searched for clinical reports, papers, and books related to tumor
      metastasis, recurrence, immunotherapy, tumor dormancy, and traditional oriental
      herbal medicine with anticancer effects. Seventy-nine (79) experimental and
      clinical articles in both Korean and English were reviewed. This study was
      conducted from March 1, 2012 to May 31, 2012. RESULTS: This approach, Tumor
      dormancy therapy, rather than seeking to remove the tumor, includes combination
      of low-dose chemotherapy, immunotherapy, immunosurveillance, and other methods to
      stabilize tumor growth and to enhance the host is immunity against disseminated
      tumor cells and thus to manage cancer as a chronic disease while maintaining
      quality of life. In particular, integrative use of Oriental herbal medicine has
      been shown to induce or maintain tumor dormancy, increase the effectiveness of
      conventional chemotherapy, improve quality of life, and prolong survival.
      CONCLUSION: Tumor dormancy therapy is a promising novel therapeutic approach that
      may be especially effective with Oriental herbal medicine. Further research is
      needed to determine its potential mechanisms and therapeutic applications.

PMID- 25780658
TI  - Anti-Oxidant and Hepatoprotective Activities of Ziziphus mucronata Fruit Extract
      Against Dimethoate-Induced Toxicity.
AB  - OBJECTIVE: The study was carried out to evaluate the hepatoprotective and
      antioxidant potential of Ziziphus mucronata (ZM) fruit extract. METHODS: The
      different types of fruit extract were prepared by soaking the dry powdered fruit
      in different solvents followed by rotary evaporation. Each extract was tested for
      its phenol content and antioxidant activities. An in vivo study was performed in
      Sprague- Dawley (SD) rats. Thirty adult male SD rats (aged 21 weeks) were divided
      into six groups of five rats each and treated as follows: The normal control (NC)
      received distilled water while the dimethoate control (DC) received 6
      mg/kg.bw.day-1 dimethoate dissolved in distilled water. The experimental groups
      E1, E2, E3, and E0 received dimethoate (6 mg/kg.bw) + ZMFM (100 mg/kg.bw-1),
      dimethoate (6 mg/kg.bw) + ZMFM (200 mg/kg.bw-1), dimethoate (6 mg/kg.bw) + ZMFM
      (300 mg/kg.bw-1), and ZMFM (300 mg/kg.bw-1) only. Both the normal control and the
      dimethoate control groups were used to compare the results. After 90 days, rats
      were sacrificed, blood was collected for biochemical assays, and livers were
      harvested for histological study. RESULTS: High phenol content was estimated, and
      2, 2- diphenyl-1-picryl hydrazyl radical (DPPH) spectrophotometric, thin layer
      chromatography (TLC) and 2, 2-Azobis-3-ethyl benzothiazoline-6-sulphonic acid
      (ABTS) assays showed a high antioxidant activity among the extracts. The
      preventive effects observed in the E1, E2 and E3 groups proved that the extract
      could prevent dimethoate toxicity by maintaining normal reduced glutathione
      (GSH), vitamin C and E, superoxide dismutase, catalase, cholineasterase and lipid
      profiles. The preventive effect was observed to be dose dependent. The EO group
      showed no extractinduced toxicity. Histological observations agreed with the
      results obtained in the biochemical studies. CONCLUSION: The study demonstrated
      that ZM methanol fruit extract is capable of attenuating dimethoate-induced
      toxicity because of its high antioxidant activity.

PMID- 25780659
TI  - Identification and Analysis of the Novel pGAPDH-w Gene Differentially Expressed
      in Wild Ginseng.
AB  - OBJECTIVE: Panax ginseng is one of the most medicinally used herbal medicines in
      the world. Wild ginseng is widely accepted to be more active than cultivated
      ginseng in chemoprevention. However, little has actually been reported on the
      differences between wild ginseng and cultivated ginseng. METHOD: To identify wild
      ginseng-specific genes, we used suppressive subtraction hybridization. RESULTS:
      We report that one of the clones isolated in this screen was the
      GAPDH(glyceraldehyde 3-phosphate dehydrogenase) gene (designated pGAPDH-w). DNA
      BLAST sequence analysis revealed that this pGAPDH-w gene contained novel
      sequences of 94 bp. RT-PCR results showed that the expression of the pGAPDH-w
      gene was significantly up-regulated in the wild ginseng as compared with the
      cultivated ginseng. CONCLUSION: The pGAPDH-w gene may be one of the important
      markers of wild ginseng.

PMID- 25780660
TI  - Effect of geumgoeshingi-whan pharmacopuncture on the blood pressure in
      spontaneously hypertensive rats.
AB  - OBJECTIVE: The aim of this experiment was to investigate the effect and the
      mechanism of Geumgoeshingi-whan (GGSGW) Pharmacopuncture at the acupoint GV 4 on
      the blood pressure in spontaneously hypertensive rats (SHR). METHODS: SHR were
      injected with normal saline solution (Control-SHR group)or GGSGW Pharmacopuncture
      (GGSGW-SHR group) at the acupoint GV 4. The systolic arterial blood pressure and
      renal parameters were measured for two weeks. RESULTS: The systolic arterial
      blood pressure was decreased significantly after GGSGW Pharmacopuncture at the
      acupoint GV 4 in SHR, followed by a significant rise in creatine clearance. The
      plasma levels of aldosterone were decreased significantly after GGSGW
      Pharmacopunctureas were the plasma levels of atrial natriuretic peptide (ANP).
      CONCLUSION: These results suggest that the blood pressure was decreased
      significantly after GGSGW Pharmacopuncture at the acupoint GV 4 in SHR and that
      the depressor response of the blood pressure was related to decreases in the
      plasma levels of aldosterone and ANP.

PMID- 25780661
TI  - Modulation of pacemaker potentials by pyungwi-san in interstitial cells of cajal
      from murine small intestine: pyungwi-san and interstitial cells of cajal.
AB  - OBJECTIVE: Pyungwi-san (PWS) plays a role in a number of physiologic and
      pharmacologic functions in many organs. Interstitial cells of Cajal (ICCs) are
      pacemaker cells that generate slow waves in the gastrointestinal (GI) tract. We
      aimed to investigate the beneficial effects of PWS in mouse small-intestinal
      ICCs. METHODS: Enzymatic digestion was used to dissociate ICCs from the small
      intestine of a mouse. The wholecell patch-clamp configuration was used to record
      membrane potentials from the cultured ICCs. RESULTS: ICCs generated pacemaker
      potentials in the GI tract. PWS produced membrane depolarization in the current
      clamp mode. Pretreatment with a Ca(2+) -free solution and a thapsigargin, a
      Ca(2+) -ATPase, inhibitor in the endoplasmic reticulum, eliminated the generation
      of pacemaker potentials. However, only when the thapsigargin was applied in a
      bath solution, the membrane depolarization was not produced by PWS. Furthermore,
      the membrane depolarizations due to PWS were inhibited not by U-73122, an active
      phospholipase C inhibitor, but by chelerythrine and calphostin C, protein kinase
      C inhibitors. CONCLUSIONS: These results suggest that PWS might affect GI
      motility by modulating the pacemaker activity in the ICCs.

PMID- 25780662
TI  - Review of cervi cornu parvum pharmacopuncture in korean medicine.
AB  - OBJECTIVE: The endpoint of this review is to investigate existing studies of
      Cervi cornu parvum(CCP) pharmacopuncture within Korean medicine journals in order
      to present a better research method in the future. METHODS: We searched all the
      papers through six Korean electrical databases that included the title of " Cervi
      cornu parvum pharmacopuncture" or " Cervi cornu parvum aqua-acupuncture".
      Articles that had been published until December 2012 were largely divided into
      experimental studies and clinical studies. RESULTS: Fifty-three (53) experimental
      studies and six clinical studies were found. The number of published articles has
      been constantly increasing. Many of the experimental studies demonstrated anti
      inflammatory effects for arthritis, and most of the clinical studies dealt with
      musculoskeletal problems. CONCLUSION: Various therapeutically significant effects
      of the CCP pharmacopuncture have been found through this review; however, more
      systematic clinical studies on the CCP pharmacopuncture seem to be necessary to
      substantially support its clinical effects.

PMID- 25780663
TI  - In-Vitro, Anti-Bacterial Activities of Aqueous Extracts of Acacia catechu
      (L.F.)Willd, Castanea sativa, Ephedra sinica stapf and shilajita mumiyo Against
      Gram Positive and Gram Negative Bacteria.
AB  - OBJECTIVE: Evaluations of the in-vitro anti-bacterial activities of aqueous
      extracts of Acacia catechu (L.F.)Willd, Castanea sativa, Ephedra sinica stapf and
      Shilajita mumiyo against gram-positive bacteria (Staphylococcus aureus,
      Streptococcus pneumonia) and gram-negative bacteria (Escherichia coli, klebsiella
      pneumoniae, Proteus mirabilis, Pseudomonas aeruginosa) are reasonable since these
      ethnomedicinal plants have been used in Persian folk medicine for treating skin
      diseases, venereal diseases, respiratory problems and nervous disorders for ages.
      METHODS: The well diffusion method (KB testing) with a concentration of 250
      MUg/disc was used for evaluating the minimal inhibitory concentrations (MIC).
      Maximum synergistic effects of different combinations of components were also
      observed. RESULTS: A particular combination of Acacia catechu (L.F.) Willd,
      Castanea sativa, Ephedra sinica stapf and shilajita mumiyo extracts possesses an
      outstanding anti-bacterial activity. It's inhibiting effect on microorganisms is
      significant when compared to the control group (P< 0.05). Staphylococcus aureus
      was the most sensitive microorganism. The highest antibacterial activity against
      gram-positive bacteria (Staphylococcus aureus, Streptococcus pneumonia) or gram
      negative bacteria (Escherichia coli, Klebsiella pneumonia, Proteus mirabilis and
      Pseudomonas aeruginosa) was exerted by formula number 2 (Table1). CONCLUSION: The
      results reveal the presence of antibacterial activities of Acacia catechu,
      Castanea sativa husk, Ephedra sp. and Mumiyo against gram-positive and gram
      negative bacteria. Synergistic effects in a combined formula, especially in
      formula number 2 (ASLAN(R)) can lead to potential sources of new antiseptic
      agents for treatment of acute or chronic skin ulcers. These results considering
      the significant antibacterial effect of the present formulation, support ethno
      pharmacological uses against diarrheal and venereal diseases and demonstrate use
      of these plants to treat infectious diseases.

PMID- 25780664
TI  - Efficacy of pharmacopuncture for treating children with physical disabilities in
      uzbekistan.
AB  - OBJECTIVE: This research was performed to investigate the efficacy of complex
      rehabilitation combined with pharmacopuncture treatment for the children with
      neuromotor system diseases. METHODS: Fifty (50) patients aged from 5 to 15 yr old
      were compared. Twenty (20) patients received conventional treatments and complex
      rehabilitation as a control group, and fifty (50) patients received complex
      rehabilitation with pharmacopuncture. At their first visits, the patients had
      checkups and neurological scales, and after 10 days of pharmacopuncture
      treatments and 55 days of rehabilitation, they also took neurological scales. We
      studied the pre and post effects of the treatment group. RESULTS: The number of
      patients with ankle joint disorder and contracture, knee joint contracture,
      steppage, horsey hoof, shoulder weakness and contracture, radio-carpal joint
      disorder and contracture, arm hypotrophia, arm atrophia, leg hypotrophia and
      total atrophia decreased after treatments. CONCLUSION: This study showed the
      efficacy of pharmacopuncture combined with complex rehabilitation for the
      treatment of neuromotor system diseases.

PMID- 25780665
TI  - Study on a Single-Dose Toxicity Test of D-Amino Acid Oxidase (DAAO) Extracts
      Injected into the Tail Vein of Rats.
AB  - OBJECTIVE: This study was performed to analyze the single-dose toxicity of D
      amino acid oxidase (DAAO) extracts. METHODS: All experiments were conducted at
      the Korea Testing & Research Institute (KTR), an institution authorized to
      perform non-clinical studies, under the regulations of Good Laboratory Practice
      (GLP). Sprague-Dawley rats were chosen for the pilot study. Doses of DAAO
      extracts, 0.1 to 0.3 cc, were administered to the experimental group, and the
      same doses of normal saline solution were administered to the control group. This
      study was conducted under the approval of the Institutional Animal Ethics
      Committee. RESULTS: In all 4 groups, no deaths occurred, and the LD50 of DAAO
      extracts administered by IV was over 0.3 ml/kg. No significant changes in the
      weight between the control group and the experimental group were observed. To
      check for abnormalities in organs and tissues, we used microscopy to examine
      representative histological sections of each specified organ, the results showed
      no significant differences in any organs or tissues. CONCLUSION: The above
      findings suggest that treatment with D-amino acid oxidase extracts is relatively
      safe. Further studies on this subject should be conducted to yield more concrete
      evidence.

PMID- 25780666
TI  - Comparison of the Amino-Acid Content in Pharmacopuncture Extracts Taken from a
      Scorpion's Body and from Its Tail.
AB  - OBJECTIVE: This study was conducted to investigate the amino-acid compositions of
      pharmacopuncture extracts taken from the body and from the tail of Buthus
      martensii Karsch, which are frequently prescribed in Oriental medicine. METHODS:
      Amino acids in hot water and 70% ethanol extracts taken from the scorpion's whole
      body and from its tail were screened by using high performance liquid
      chromatography (HPLC). The experiments were performed with linearity, precision
      and accuracy. RESULTS: The results of the amino-acid-composition analysis showed
      that the Buthus martensii Karsch extracts contained various amino acids such as
      aspartic acid, histidine, alanine, tyrosine, and cystine. The amino-acid analysis
      showed that the hot water extract was more beneficial than the ethanol extract,
      except for histidine. The amino acids from the tail and the body of the scorpion
      were compared, and the concentration of aspartic acid in the extract from the
      scorpion's tail was two times that found in the extract from its body. The
      results of validation experiments were all satisfactory. CONCLUSION: Studies on
      the ingredients in extracts from a scorpion other than buthotoxin may demonstrate
      that the antiepileptic efficacy, anticancer activity, antithrombotic action and
      analgesic effect are enhanced. Using only the tail of the scorpion when
      pharmacopuncture is dispensed may be beneficial because the extracts from the
      tail of the scorpion have higher potency than those from the whole body.

PMID- 25780667
TI  - Anti-Allergic Effect of Ulmus davidiana Cortex on Contact Dermatitis Induced by
      Dinitrofluoro- Benzene in Mice.
AB  - OBJECTIVE: The root bark of Ulmus davidiana var. Japonica (Ulmi Radicis cortex,
      URC) is a medicinal herb used for promoting diuresis and treating dampness. In
      Korea, URC has long been used as an efficacious therapy for inflammation, burns,
      frostbite and skin diseases such as eczema and psoriasis. METHODS: In the present
      study, we used 1-fluoro-2,4- dinitrofluorobenzene (DNFB)-induced contact
      dermatitis (CD) mouse model to investigate the antiallergic and the anti
      inflammatory effects of URC on skin lesion, histopathological changes and
      specific antibody production. RESULTS: URC treatment, 10 mg/mL, effectively
      inhibited skin lesions induced by repeated paintings with DNFB. In the
      histopathological observation, topical application of URC inhibited spongiosis.
      In addition, URC lowered the production levels of total immunoglobulin and IgG2a
      in serum. CONCLUSION: These data indicate that URC has an anti-inflammatory
      effect that produces an improvement of skin lesions in CD mice.

PMID- 25780668
TI  - Isolation from Gloydius blomhoffii siniticus Venom of a Fibrin(ogen)olytic Enzyme
      Consisting of Two Heterogenous Polypeptides.
AB  - OBJECTIVE: This study was undertaken to isolate a fibrin(ogen)olytic enzyme from
      the snake venom of Gloydius blomhoffii siniticus and to investigate the enzymatic
      characteristics and hemorrhagic activity of the isolated enzyme as a potential
      pharmacopuncture agent. METHODS: The fibrinolytic enzyme was isolated by using
      chromatography, sodium dodecyl sulfatepolyacrylamide gel electrophoresis, and
      fibrin plate assay. The characteristics of the enzyme were determined by using
      fibrin plate assay, protein hydrolysis analysis, and hemorrhage assay. Its amino
      acid composition was determined. RESULTS: The fibrin(ogen)olytic enzyme with the
      molecular weight of 27 kDa (FE-27kDa) isolated from G. b. siniticus venom
      consisted of two heterogenous disulfide bond-linked polypeptides with the
      molecular weights of 15 kDa and 18 kDa. When more than 20 MUg of FE-27kDa was
      applied on the fibrin plate, fibrinolysis zone was formed as indicating its
      fibrinolytic activity. The fibrinolytic activity was inhibited completely by
      phenylmethanesulfonylfluoride (PMSF) and ethylenediaminetetraacetic acid (EDTA)
      and partially by thiothreitol and cysteine. Metal ions such as Hg(2+) and Fe(2+)
      inhibited the fibrinolytic activity completely, but Mn(2+) did not. FE-27kDa
      preferentially hydrolyzed alpha- chain of fibrinogen and slowly hydrolyzed beta-
      chain, but did not hydrolyze gamma- chain. High-molecular-weight polypeptides of
      gelatin were hydrolyzed partially into polypeptides with molecular weights of
      more than 45 kDa. A dosage of more than 10 MUg of FE- 27kDa per mouse was
      required to induce hemorrhage beneath the skin. CONCLUSION: FE-27kDa was a serine
      proteinase consisting of two heterogeneous polypeptides, hydrolyzed fibrin,
      fibrinogen, and gelatin, and caused hemorrhage beneath the skin of mouse. This
      study suggests that the potential of FE-27kDa as pharmacopuncture agent should be
      limited due to low fibrinolytic activity and a possible side effect of
      hemorrhage.

PMID- 25780669
TI  - Effects of Ulmi Pumilae Cortex on AGS Gastric Cancer Cells.
AB  - OBJECTIVE: Ulmi Pumilae Cortex(UPC) is a deciduous tree with uneven pinnate
      leaves and is classified as a subfamily of Ulmuceae and contains many
      pharmacologically active constituents. The aim of this study was to investigate
      the effects of UPC on the growth and survival of AGS cells, the most common human
      gastric adenocarcinoma cell lines. METHODS: The AGS cells were treated with
      varying concentrations of UPC. Analyses of the sub G1, caspase-3 activity, and
      mitochondrial depolarization were conducted to determine whether AGS cell death
      occured by apoptosis. Furthermore, to identify the role of the transient receptor
      potential melastatin (TRPM) 7 channels in AGS cell growth and survival, we used
      human embryonic kidney (HEK) 293 cells overexpressed with TRPM7 channels.
      RESULTS: The addition of UPC to a culture medium inhibited AGS cell growth and
      survival. Experimental results showed that the sub G1, caspase-3 activity, and
      mitochondrial depolarization were increased. Furthermore, TRPM7 channel
      overexpression in HEK 293 cells exacerbated UPC-induced cell death. CONCLUSION:
      These findings indicate that UPC inhibits the growth and survival of gastric
      cancer cells due to a blockade of the TRPM7 channel activity. Therefore, UPC is a
      potential drug for treatment of gastric cancer, and TRPM7 channels may play an
      important role in survival in cases of gastric cancer.

PMID- 25780670
TI  - Effects of Dioscoreae Rhizoma (SanYak) on Peripheral Neuropathy and its Safety.
AB  - OBJECTIVES: This study aimed to evaluate the evidence available in the literature
      for the safety and efficacy of Dioscoreae Rhizoma(DR) for the treatment of
      peripheral neuropathy. METHODS: Literature searches were performed in MEDLINE and
      three Korean medical databases up to April 2013. All studies evaluating the
      effects on peripheral neuropathy or the safety of DR monopreparations were
      considered. RESULTS: Three studies - DR extract per os (po) on diabetic
      neuropathy in mice, DR extract injection on the peripheral sciatic nerve after
      crush injury in rats and DR extract injection to patients with peripheral facial
      paralysis proved that DR treatments were effective for the treatment of nerve
      injuries. CONCLUSIONS: In conclusion, we found the DR has a strong positive
      potential for the treatment of peripheral neuropathy, but studies addressing
      direct factors related to the nerve still remain insufficient.

PMID- 25780671
TI  - Post-cancer Treatment with Condurango 30C Shows Amelioration of Benzo[a]pyrene
      induced Lung Cancer in Rats Through the Molecular Pathway of Caspa- se-3-mediated
      Apoptosis Induction: -Anti-lung cancer potential of Condurango 30C in rats.
AB  - OBJECTIVES: The present investigation aimed at examining if post-cancer treatment
      with a potentized homeopathic drug, Condurango 30C, which is generally used to
      treat oesophageal cancer, could also show an ameliorating effect through
      apoptosis induction on lung cancer induced by benzo[a]pyrene (BaP) in white rats
      (Rattus norvegicus). METHODS: Lung cancer was induced after four months by
      chronic feeding of BaP to rats through gavage at a dose of 50 mg/kg body weight
      for one month. After four months, the lung-cancer-bearing rats were treated with
      Condurango 30C for the next one (5(th)), two (5(th)-6(th)) and three (5(th)
      7(th)) months, respectively, and were sacrificed at the corresponding time-
      points. The ameliorating effect, if any, after Condurango 30C treatment for the
      various periods was evaluated by using protocols such as histology, scanning
      electron microscopy (SEM), annexinV-FITC/PI assay, flow cytometry of the
      apoptosis marker, DNA fragmentation, reverse transcriptase-polymerase chain
      reaction (RT-PCR), immunohistochemistry, and western blot analyses of lung tissue
      samples. RESULTS: Striking recovery of lung tissue to a near normal status was
      noticed after post-cancerous drug treatment, as evidenced by SEM and histology,
      especially after one and two months of drug treatment. Data from the annexinV
      FITC/PI and DNA fragmentation assays revealed that Condurango 30C could induce
      apoptosis in cancer cells after post-cancer treatment. A critical analysis of
      signalling cascade, evidenced through a RT-PCR study, demonstrated up-regulation
      and down-regulation of different pro- and anti-apoptotic genes, respectively,
      related to a caspase-3-mediated apoptotic pathway, which was especially
      discernible after one-month and two- month drug treatments. Correspondingly,
      Western blot and immunohistochemistry studies confirmed the ameliorative
      potential of Condurango 30C by its ability to down-regulate the elevated
      epidermal growth factor receptor (EGFR) expression, a hallmark of lung cancer.
      CONCLUSION: The overall result validated a positive effect of Condurango 30C in
      ameliorating lung cancer through caspase-3-mediated apoptosis induction and EGFR
      down-regulation.

PMID- 25780672
TI  - Antihyperlipidemic Activity of the Ethyl-acetate Fraction of Stereospermum
      Suaveolens in Streptozotocin-induced Diabetic Rats.
AB  - OBJECTIVES: Dyslipidemia in diabetes mellitus is a significant risk factor for
      the development of cardiovascular complications. The aim of this study was to
      evaluate the effect of the ethyl-acetate fraction of an ethanolic extract from
      Streospermum suaveolens on lipid metabolism in streptozotocin (STZ)-induced
      diabetic rats. METHODS: Diabetes was induced by intraperitonial injection of STZ
      (50 mg/kg). Diabetic rats were treated with an ethyl-acetate fraction orally at
      doses of 200 and 400 mg/kg daily for 14 days. On the 15(th) day, serum lipid
      profiles, such as total cholesterol (TC), triglycerides (TG), low-density
      lipoprotein (LDL), and high-density lipoprotein (HDL), were estimated in
      experimental rats. The atherogenic (AI) and the coronary risk (CRI) indices were
      also evaluated. RESULTS: The ethyl-acetate fraction at doses of 200 and 400 mg/kg
      significantly (P< 0.001) and dose-dependently reduced serum cholesterol,
      triglycerides and LDL, but increased HDL towards near normal levels as compared
      to diabetic control rats. The fraction also significantly (P< 0.001) lowered the
      atherogenic index (AI) and coronary risk index (CAI) in a dose-dependent manner.
      CONCLUSION: The present study demonstrated that the ethyl-acetate fraction of
      Stereospermum suaveolens exhibits a potent antihyperlipidemic activity in
      hyperglycemic rats and suggests that the plant may have therapeutic value in
      treating the diabetic complication of hyperlipidemia.

PMID- 25780673
TI  - Differential Expression of Gene Profiles in MRGX-treated Lung Cancer.
AB  - OBJECTIVES: Modified regular ginseng extract (MRGX) has stronger anti-cancer
      activity-possessing gensenoside profiles. METHODS: To investigate changes in gene
      expression in the MRGX-treated lung cancer cells (A549), we examined genomic data
      with cDNA microarray results. After completing the gene-ontology-based analysis,
      we grouped the genes into up-and down-regulated profiles and into ontology
      related regulated genes and proteins through their interaction network. RESULTS:
      One hundred nine proteins that were up- and down-regulated by MRGX were queried
      by using IPA. IL8, MMP7 and PLAUR and were found to play a major role in the anti
      cancer activity in MRGX-treated lung cancer cells. These results were validated
      using a Western blot analysis and a semi-quantitative reverse transcription
      polymerase chain reaction (RT-PCR) analysis. CONCLUSIONS: Most MRGX-responsive
      genes are up-regulated transiently in A549 cells, but down-regulated in a
      sustained manner in lung cancer cells.

PMID- 25780674
TI  - Buxus Microphylla var. Koreana Nakai Extract for the Treatment of Gastric Cancer.
AB  - OBJECTIVES: Buxus Microphylla var. Koreana Nakai Extract (BMKNE) is used as a
      folk remedy for malaria and veneral disease. In the present study, we
      investigated the effects of BMKNE in the growth and the survival of AGS cells,
      the most common human gastric adenocarcinoma cell lines. METHODS: The AGS cells
      were treated with varying concentrations of BMKNE. Analyses of the sub G1 peak,
      the caspase-3 and -9 activities, and the mitochondrial depolarization were
      conducted to determine whether AGS cell death occured by apoptosis. Also, to
      identify the role of transient receptor potential melastatin (TRPM) 7 channels in
      AGS cell growth and survival, we used human embryonic kidney (HEK) 293 cells
      overexpressed with TRPM7 channels. RESULTS: Experimental results showed that the
      sub G1 peak, the caspase-3 and -9 activities, and the mitochondrial
      depolarization were increased. Therefore, BMKNE was found to induce the apoptosis
      of these cells, and this apoptosis was inhibited by SB203580 (a p38 mitogen
      activated protein kinase (MAPK) inhibitor), and by a c-jun NH2-terminal kinase
      (JNK) II inhibitor. Furthermore, BMKNE inhibited TRPM7 currents and TRPM7 channel
      over-expressions in HEK 293 cells, exacerbating BMKNE-induced cell death.
      CONCLUSIONS: These findings indicate that BMKNE inhibits the growth and the
      survival of gastric cancer cells due to a blockade of the TRPM7 channel's
      activity and MAPK signaling. Therefore, BMKNE is a potential drug for treatment
      of gastric cancer, and both the TRPM7 channel and MAPK signaling may play an
      important role in survival in gastric cancer cells.

PMID- 25780675
TI  - Clinical study of lumbar spine stenosis treated by using acupotomy combined with
      oriental medical treatments.
AB  - OBJECTIVES: The aim of this study is to evaluate the effect of acupotomy in
      patients with degenerative lumbar spine stenosis. METHODS: A total of 437
      patients who had been diagnosed as having lumbar spine stenosis and who had been
      admitted to Daejeon Oriental hospital from June 1, 2008, to September 31, 2012,
      were included in this study. The patients underwent acupotomy once, twice or
      three times on the lumbar spine, according to their symptoms. Then, the patients
      were asked to complete the verbal numeric rating scale (VNRS) and the oswestry
      disability index (ODI) before and after acupotomy and underwent a global
      assessment. The resulting data were analyzed. RESULTS: The gender ratio of the
      participants was 1:1.54, and the mean age was 65 +/- 10.0 yr. The number of
      patients over the age of 65 yr was less than that of the patients under the age
      of 65 yr in the ratio of 1:1.3. The average disease period was 30.17 +/- 56.63
      months. The verbal numeric rating scale (VNRS) significantly decreased from 10 to
      an average of 7.10 +/- 2.50 after one acupotomy, 6.30 +/- 2.60 after two
      acupotomies, and 5.50 +/- 2.50 after three acupotomies. The ODI was significantly
      decrease from 20.60 +/- 8.70 to 17.80 +/- 8.60 after once acupotomy, 17.10 +/-
      8.50 after two acupotomies, and 16.70 +/- 8.60 after three acupotomies. High
      scores were also observed on the global assessment. CONCLUSION: These results
      provide evidence that acupotomy is effective to relieve pain and to improve
      quality of life in patients with degenerative lumbar spinal stenosis.

PMID- 25780676
TI  - Clinical review of the effects of hominis placental pharmacopuncture in the
      treatment of facial spasm patients.
AB  - OBJECTIVES: The main purpose of this research is to investigate the effect of
      treatment with Hominis Placental pharmacopuncture (HPP) for 32 patients with
      hemifacial spasm. METHODS: We treated facial spasm patients with acupuncture and
      HPP at Sabaek (ST2), Seung-eup (ST1), Gwallyeo (SI18), Chanjuk (BL2), Sajukgong
      (TE23), Hagwan (ST7), Hyeopgeo (ST6), Jichang (ST4), Wan-gol (SI4) and Yepung
      (TE17), and we investigated the effect by using Scott's scale. The data were
      analyzed by using the SPSS/10.0 for windows program with descriptive statistics,
      the paired t-test, and the Shapiro-Wilk normality test. RESULTS: After treatment,
      the grade of the spasm's intensity based on Scott's description were decreased
      significantly. About 72% of the patients felt that the combination treatment had
      produced excellent results. CONCLUSION: These data suggested that HPP can be
      useful for treating facial spasm patients.

PMID- 25780677
TI  - Evidence of an Epigenetic Modification in Cell-cycle Arrest Caused by the Use of
      Ultra-highly-diluted Gonolobus Condurango Extract.
AB  - OBJECTIVES: Whether the ultra-highly-diluted remedies used in homeopathy can
      effectively bring about modulations of gene expressions through
      acetylation/deacetylation of histones has not been explored. Therefore, in this
      study, we pointedly checked if the homeopathically-diluted anti-cancer remedy
      Condurango 30C (ethanolic extract of Gonolobus condurango diluted 10(-60) times)
      was capable of arresting the cell cycles in cervical cancer cells HeLa by
      triggering an epigenetic modification through modulation of the activity of the
      key enzyme histone deacetylase 2 vis-a-vis the succussed alcohol (placebo)
      control. METHODS: We checked the activity of different signal proteins (like
      p21(WAF), p53, Akt, STAT3) related to deacetylation, cell growth and
      differentiation by western blotting and analyzed cell-cycle arrest, if any, by
      fluorescence activated cell sorting. After viability assays had been performed
      with Condurango 30C and with a placebo, the activities of histone de-acetylase
      (HDAC) enzymes 1 and 2 were measured colorimetrically. RESULTS: While Condurango
      30C induced cytotoxicity in HeLa cells in vitro and reduced HDAC2 activity quite
      strikingly, it apparently did not alter the HDAC1 enzyme; the placebo had no or
      negligible cytotoxicity against HeLa cells and could not alter either the HDAC 1
      or 2 activity. Data on p21(WAF), p53, Akt, and STAT3 activities and a cell-cycle
      analysis revealed a reduction in DNA synthesis and G1-phase cell-cycle arrest
      when Condurango 30C was used at a 2% dose. CONCLUSION: Condurango 30C appeared to
      trigger key epigenetic events of gene modulation in effectively combating cancer
      cells, which the placebo was unable to do.

PMID- 25780678
TI  - Role of glyco-persica((r)) in targeting diabetes type 2: an integrative approach.
AB  - OBJECTIVES: The objective of this study was to examine how an integrated approach
      to type 2 diabetes mellitus treatment could improve glycemic control and immune
      potentiating activities adherent to oral hypoglycemic agents along with a
      botanical compound, among primary care patients. METHODS: In this study, we used
      the self-control and the group-control methods. Candidates meeting the trial
      conditions were selected from among volunteers who had taken the test substance
      for 45 days. During the trial, all groups were on a controlled diet; neither were
      the original medications nor their dosages changed. RESULTS: The results showed
      that the botanical compound (Glyco-Persica((r))) significantly reduced the main
      clinical symptoms in diabetes type 2. In the treatment group, 36 of 52 patients
      (69.23%) and in the control group 10 of 52 patients (19.23%) showed reduced
      symptoms, and this difference was statistically significant (P< 0.05). The
      fasting blood sugar in the treatment group after treatment compared with that
      before treatment and with that in the control group after treatment was
      statistically different (P< 0.05). The post-prandial glucose in the treatment
      group after treatment was significantly different from that before treatment and
      from that in the control group after treatment (P< 0.05); the post-prandial blood
      sugar in the treatment group was reduced by 8.98%. CONCLUSIONS: The results
      revealed that the botanical compound (Glyco-Persica((r))) has significant
      hypoglycemic properties which affect main clinical symptoms in diabetes type 2.
      Body weight, blood pressure, heart rate, routine blood, stool and urine tests
      showed no meaningful negative changes after the course of treatment. There was no
      significant adverse reaction during the trial.

PMID- 25780679
TI  - Single Intramuscular-dose Toxicity of Anti-inflammatory Pharmacopuncture in Rats.
AB  - OBJECTIVES: This study was performed to analyze the toxicity of the test
      substance, anti-inflammatory pharmacopuncture (AIP), when used as a single
      intramuscular-dose in 6-week-old, male and female Sprague-Dawley rats and to find
      the lethal dose. METHODS: The experiment was conducted at Biotoxtech according to
      Good Laboratory Practices. Twenty (20) female and 20 male Spague-Dawley rats were
      divided into 4 groups of five 5 female and 5 male animals per group. The rats in
      the three experimental groups received single intramuscular injections with 0.1
      ?, 0.5-? and 1.0-?/animal doses of AIP, Groups 2, 3, and 4, respectively, and the
      control group, Group 1, received a single intramuscular injection with a 1.0-?
      dose of normal saline. Clinical signs were observed and body weight measurements
      were carried out for 14 days following the injections. At the end of the
      observation period, hematology, clinical chemistry, histopathological tests and
      necropsy were performed on the injected parts. RESULTS: No deaths occurred in any
      of the groups. Also, histopathological tests showed that AIP had no effect on the
      injected parts in terms of clinical signs, body weight, hematology, clinical
      chemistry, and necropsy. CONCLUSIONS: As a result of single intramuscular-dose
      tests of the test substance AIP in 4 groups of rats, the lethal dose for both
      males and females exceeded 1.0?/animal. Therefore, AIP is a relatively safe
      pharmacopuncture that can be used for treatment, but further studies should be
      performed.

PMID- 25780680
TI  - Calculus Bovis-Fel Uris-Moschus Pharmacopuncture's Effect on Regional Cerebral
      Blood Flow and Mean Arterial Blood Pressure in Rats.
AB  - OBJECTIVES: This study was designed to investigate the effects of Calculus Bovis
      Fel Uris-Moschus pharmacopuncture(BUM) on the regional cerebral blood flow (rCBF)
      and the mean arterial blood pressure (MABP) in normal and cerebral ischemic rats
      and to investigate a possible pathway involved in the effects of BUM. METHODS:
      The changes in the rCBF and the MABP following BUM into Fengfu (GV16) were
      determined by using a laser-Doppler flow meter and a pressure transducer,
      respectively. RESULTS: BUM significantly increased the rCBF and decreased the
      MABP in normal rats in a dose-dependent manner. The effect on the rCBF was
      significantly inhibited by pretreatment with methylene blue (0.01 mg/kg,
      intraperitoneal), an inhibitor of guanylate cyclase, but was not affected by
      pretreatment with indomethacin (1 mg/kg, intraperitoneal), an inhibitor of
      cyclooxygenase. The BUM-induced decrease of the MABP was changed neither by
      methylene blue nor by indomethacin pretreatment. In the cerebral ischemic rats,
      the rCBF was stably increased upon cerebral reperfusion in the BUM group in
      contrast to the rapid and marked increase in the control group. CONCLUSION: This
      study demonstrated that BUM into Fengbu (GV16) increased the rCBF in a dose
      dependent manner in the normal state; furthermore, it improved the stability of
      the rCBF in the ischemic state upon reperfusion. Also, the effects of BUM on the
      rCBF were attenuated by inhibition of guanylate cyclase, suggesting that the
      effects involved the guanylate cyclase pathway.

PMID- 25780681
TI  - Shengmaisan regulates pacemaker potentials in interstitial cells of cajal in
      mice.
AB  - OBJECTIVES: Shengmaisan (SMS) is a traditional Chinese medicine prescription
      widely used for the treatment of diverse organs in Korea. The interstitial cells
      of Cajal (ICCs) are pacemaker cells that play an important role in the generation
      of coordinated gastrointestinal (GI) motility. We have aimed to investigate the
      effects of SMS in the ICCs in the mouse small intestine. METHODS: To dissociate
      the ICCs, we used enzymatic digestions from the small intestine in a mouse. After
      that, the ICCs were identified immunologically by using the anti-c-kit antibody.
      In the ICCs, the electrophysiological whole-cell patch-clamp configuration was
      used to record pacemaker potentials in the cultured ICCs. RESULTS: The ICCs
      generated pacemaker potentials in the mouse small intestine. SMS produced
      membrane depolarization with concentration-dependent manners in the current clamp
      mode. Pretreatment with a Ca(2+) free solution and thapsigargin, a Ca(2+)-ATPase
      inhibitor in the endoplasmic reticulum, stopped the generation of the pacemaker
      potentials. In the case of Ca(2+)-free solutions, SMS induced membrane
      depolarizations. However, when thapsigargin in a bath solution was applied, the
      membrane depolarization was not produced by SMS. The membrane depolarizations
      produced by SMS were inhibited by U-73122, an active phospholipase C (PLC)
      inhibitors. Furthermore, chelerythrine and calphostin C, a protein kinase C (PKC)
      inhibitors had no effects on SMS-induced membrane depolarizations. CONCLUSIONS:
      These results suggest that SMS might affect GI motility by modulating the
      pacemaker activity through an internal Ca(2+)- and PLC-dependent and PKC
      independent pathway in the ICCs.

PMID- 25780682
TI  - Bee venom pharmacopuncture responses according to sasang constitution and gender.
AB  - OBJECTIVES: The current study was performed to compare the bee venom
      pharmacopuncture skin test reactions among groups with different sexes and Sasang
      constitutions. METHODS: Between July 2012 and June 2013, all 76 patients who
      underwent bee venom pharmacopuncture skin tests and Sasang constitution diagnoses
      at Oriental Medicine Hospital of Sangji University were included in this study.
      The skin test was performed on the patient's forearm intracutaneously with 0.05
      ml of sweet bee venom (SBV) on their first visit. If the patients showed a
      positive response, the test was discontinued. On the other hand, if the patient
      showed a negative response, the test was performed on the opposite forearm
      intracutaneously with 0.05 ml of bee venom pharmacopuncture 25% on the next day
      or the next visit. Three groups were made to compare the differences in the bee
      venom pharmacopuncture skin tests according to sexual difference and Sasang
      constitution: group A showed a positive response to SBV, group B showed a
      positive response to bee venom pharmacopuncture 25%, and group C showed a
      negative response on all bee venom pharmacopuncture skin tests. Fisher's exact
      test was performed to evaluate the differences statistically. RESULTS: The
      results of the bee venom pharmacopuncture skin tests showed no significant
      differences according to Sasang constitution (P = 0.300) or sexual difference (P
      = 0.163). CONCLUSION: No significant differences on the results of bee venom
      pharmacopuncture skin tests were observed according to two factors, Sasang
      constitution and the sexual difference.

PMID- 25780683
TI  - Sa-am Five-element Acupuncture and Hwangyeon- haedoktang Pharmacopuncture
      Treatment for an Essential Tremor: Three Case Reports.
AB  - The purpose of this study was to report the effect of a combination of Sa-am five
      element acupuncture and eight-principle pharmacopuncture (EPP) for the treatment
      of an essential tremor (ET). This study reviewed the medical records treated at
      OO Korean medical hospital for ET by using diverse types of acupuncture without
      herbal medicine, other types of physical therapy, and western medication related
      ET or Parkinson's disease and was performed after the approval of the
      institutional review board (IRB). The three cases that were finally selected were
      then extracted and reviewed. The three cases that were finally selected involved
      three women in their 70s to 80s. The evaluation of the progress was made by using
      the numeric rating scale. A combined treatment, the method of liver excess (),
      from amongSa-am five-element acupuncture, and Hwangyeonhaedoktang ePP at CV23 and
      CV17, was applied to all cases. In all three cases, the ET was improved, and
      recurred ETs improved with the same treatment. The results suggest that the
      combined treatment of Sa-am five-element acupuncture and Hwangyeonhaedoktang ePP
      may be effective for treating an ET, even though this conclusion is based on only
      three cases. 

PMID- 25780684
TI  - Effects of Salviae Miltiorrhizae Radix Hot Aqueous Extract on Nitric Oxide and
      Prostaglandin E2 Production and on 1,1-diphenyl-2-picryl hydrazyl Radical
      Scavenging in Macrophages.
AB  - OBJECTIVES: The objective of this study is to investigate the effects of Salviae
      Miltiorrhizae Radix hot aqueous extract on nitric oxide (NO) and prostaglandin E2
      (PGE2 ) production and on 1,1-diphenyl-2-picryl hydrazyl (DPPH) free-radical
      scavenging in macrophages. METHODS: Salviae Miltiorrhizae Radix(300 g) was heated
      at 100C with distilled water (2 L) for 4 hours. The extract was filtered and
      concentrated to 100 mL by using a rotary evaporator, was frozen at -80C, and was
      then freeze-dried by using a freezing-drying system. The RAW 264.7 macrophage was
      subcultured by using 10-?/mL lipopolysaccharide (LPS). In order to evaluate
      cytotoxicity, we performed (3-(4,5-dimrthylthiazol-2-yl)-2,5-diphenyltetrazolium
      bromide) (MTT) assays and measured the cell viability. The NO production was
      measured by using Griess assays, and the PGE2 production was measured by using
      enzyme immunoassays. The antioxidant activity, the DPPH free-radical scavenging
      capability, was measured by using the DPPH method. RESULTS: Cell viability with
      the 1-, 5-, 25-, 125- and 625-?/mL Salviae Miltiorrhizae Radix hot aqueous
      extract was not significantly decreased compared to the cell viability without
      the extract. When 125 and 625 ?/mL of Salviae Miltiorrhizae Radix hot aqueous
      extract were used, NO production in LPS-stimulated RAW 264.7 macrophages was
      significantly inhibited compared to that in the control group. When 25, 125, and
      625 ?/mL of Salviae Miltiorrhizae Radix hot aqueous extract were used, PGE2
      production in LPS-stimulated RAW 264.7 macrophages was significantly inhibited
      compared to that in the control group. The 125- and 625-?/mL Salviae
      Miltiorrhizae Radix hot aqueous extracts had high DPPH free-radical scavenging
      capabilities in RAW 264.7 macrophages. CONCLUSION: This study indicates that
      Salviae Miltiorrhizae Radix hot aqueous extract suppresses NO and PGE2 production
      and improves DPPH free-radical scavenging capability. Thus, it seems that Salviae
      Miltiorrhizae Radix hot aqueous extract may have an anti-inflammation effect and
      antioxidant activity.

PMID- 25780685
TI  - Serum Biochemical, Histopathology and SEM Analyses of the Effects of the Indian
      Traditional Herb Wattakaka Volubilis Leaf Extract on Wistar Male Rats.
AB  - OBJECTIVES: The present study investigated the protective effect of Wattakaka
      (W.) volubilis leaf extract against streptozotocin (STZ)-induced diabetes in
      rats. METHODS: Male Wistar rats were divided into five groups (with six rats in
      each group) and were fed ad libitum. The rats were fasted for sixteen hours
      before diabetes was induced by injecting a single dose of 90 mg/kg body weight of
      STZ in 0.9-percent normal saline through an intraperitoneal route. The five
      groups were as follows: Group 1: normal control (saline-treated), Group 2:
      untreated diabetic rats, Groups 3 and 4: diabetic rats treated orally with
      petroleum ether cold maceration extract (PEME) of W. volubilis(50 and 100 mg/kg
      body weight), and Group 5: diabetic rats treated orally with metformin (250 mg/kg
      body weight). All rats received treatment for 21 days. For the STZ-induced
      diabetic rats, the blood-glucose, alpha-amylase, total protein and alanine
      transaminase (ALT) levels were measured on days 7,14 and 21 of the treatment with
      PEME of W. volubilis and the treatment with metformin. Histopathological changes
      in the liver were examined with hematoxylin-eosin staining. Morphological changes
      in the liver were also examined with glutaraldehyde fixation. RESULTS: The
      treatments with PEME of W. volubilis and with metformin in experimental rats by
      oral injections for 21 days produced reductions in the levels of serum
      biochemical markers. Histopathology and scanning electron microscopy results
      showed that the administrations of PEME of W. volubilis and of metformin
      suppressed the generation of abnormal liver cells in the STZ-treated rats.
      CONCLUSION: These results suggest that both PEME of W. volubilis and metformin
      have a protective effect against STZ-induced diabetes.

PMID- 25780686
TI  - Changes in the Laboratory Data for Cancer Patients Treated with Korean-medicine
      based Inpatient Care.
AB  - OBJECTIVES: The study aimed to determine changes in laboratory data for cancer
      patients receiving Korean medicine (KM) care, with a focus on patients'
      functional status, cancer-coagulation factors and cancer immunity. METHODS: We
      conducted an observational study of various cancer patients in all stages
      admitted to the East-West Cancer Center (EWCC), Dunsan Korean Hospital of Daejeon
      University, from Mar. 2011 to Aug. 2011. All patients were under the center's
      multi-modality Korean-medicine-based inpatient cancer care program. The
      hospitalization stay at EWCC ranged from 9 to 34 days. A total of 80 patients
      were followed in their routine hematologic laboratory screenings performed before
      and after hospitalization. Patients were divided into three groups depending on
      the status of their treatment: prevention of recurrence and metastasis group,
      Korean medicine (KM) treatment only group, and combination of conventional and KM
      treatment group. The lab reports included natural killer (NK) cell count (CD16 +
      CD56), fibrinogen, white blood cell (WBC), lymphocytes, monocytes, neutrophil,
      red blood cell (RBC), hemoglobin, platelet, Erythrocyte Sedimentation Rate (ESR),
      and Eastern Cooperative Oncology Group (ECOG) performance status. RESULTS: With a
      Focus on patients' functional status, cancer-coagulation factors and cancer
      immunity, emphasis was placed on the NK cell count, fibrinogen count, and ECOG
      scores. Data generally revealed decreased fibrinogen count, fluctuating NK cell
      count and decreased ECOG, meaning improved performance status in all groups. The
      KM treatment only group showed the largest decrease in mean fibrinogen count and
      the largest increase in mean NK cell count. However, the group's ECOG score
      showed the smallest decrease, which may be due to the concentration of late
      cancer-stage patients in that particular group. CONCLUSIONS: Multi-modality KM
      inpatient care may have positive effect on lowering the cancer coagulation factor
      fibrinogen, but its correlation with the change in the NK cell count is not
      clear.

PMID- 25780687
TI  - Single Intramuscular-dose Toxicity of Water soluble Carthmi-Flos herbal
      acupuncture (WCF) in Sprague-Dawley Rats.
AB  - OBJECTIVES: This experiment was conducted to examine the toxicity of Water
      soluble Carthmi-Flos herbal acupuncture (WCF) by administering a single
      intramuscular dose of WCF in 6-week-old, male and female Sprague-Dawley rats and
      to find the lethality dose for WCF. METHODS: The experiment was conducted at
      Biotoxtech according to Good Laboratory Practices under a request by the Korean
      Pharmacopuncture Institute. This experiment was performed based on the testing
      standards of "Toxicity Test Standards for Drugs" by the Ministry of Food and Drug
      Safety. Subjects were divided into 4 groups: 1 control group in which normal
      saline was administered and 3 test groups in which 0.1, 0.5 or 1.0 mL of WCF was
      administered; a single intramuscular dose was injected into 5 males and 5 females
      in each group. General symptoms and body weights were observed/measured for 14
      days after injection. At the end of the observation period, hematological and
      clinical chemistry tests were performed, followed by necropsy and
      histopathological examinations of the injected sections. RESULTS: No mortalities
      were observed in any group. Also, symptoms, body weight, hematology, clinical
      chemistry and necropsy were not affected. However, histopathological examination
      of the injected part in one female in the 1.0-mL group showed infiltration of
      mononuclear cells and a multi-nucleated giant cell around eosinophilic material.
      CONCLUSION: Administration of single intramuscular doses of WCF in 3 groups of
      rats showed that the approximate lethal dose of WCF for all rats was in excess of
      1.0 mL, as no mortalities were observed for injections up to and including 1.0
      mL.

PMID- 25780688
TI  - Single Dose Toxicity of Chukyu (spine-healing) Pharmacopuncture Injection in the
      Muscle of Rats.
AB  - OBJECTIVES: This study was performed to analyze the single dose toxicity of
      Chukyu (spine-healing) pharmacopuncture. METHODS: All experiments were conducted
      at the Biotoxtech, an institution authorized to perform non-clinical studies
      under the regulations of Good Laboratory Practice (GLP) regulations. Sprague
      Dawley rats were chosen for the pilot study. Doses of Chukyu (spine-healing)
      pharmacopuncture, 0.1, 0.5 and 1.0 mL, were administered to the experimental
      groups, and a dose of normal saline solution, 1.0 mL, was administered to the
      control group. This study was conducted under the approval of the Institutional
      Animal Ethic Committee. RESULTS: No deaths or abnormalities occurred in any of
      the four groups. No significant changes in weight, hematological parameters or
      clinical chemistry between the control group and the experimental groups were
      observed. To check for abnormalities in organs and tissues, we used microscopy to
      examine representative histological sections of each specified organ; the results
      showed no significant differences in any of the organs or tissues except in one
      case, where interstitial infiltrating macrophages were found in one female rat in
      the 0.5-mL/animal experimental group. CONCLUSION: The above findings suggest that
      treatment with Chukyu (spine-healing) pharmacopuncture is relatively safe.
      Further studies on this subject are needed to yield more concrete evidence.

PMID- 25780689
TI  - Isolation and Characterization of a 32-kDa Fibrinolytic Enzyme (FE-32kDa) from
      Gloydius blomhoffii siniticus Venom: Fibrinolytic Enzyme from Gloydius blomhoffii
      siniticus Venom.
AB  - OBJECTIVES: This study was undertaken to isolate a fibrinolytic enzyme from the
      snake venom of Gloydius blomhoffii siniticus and to investigate its enzymatic
      characteristics and hemorrhagic activity as a potential pharmacopuncture agent.
      METHODS: The fibrinolytic enzyme was isolated by using chromatography, sodium
      dodecyl sulfate-polyacrylamide gel electrophoresis, and fibrin plate assay. The
      characteristics of the enzyme were investigated using fibrin plate assay, protein
      hydrolysis analysis, and hemorrhage assay. Its amino acid composition was
      determined. RESULTS: The fibrinolytic enzyme with the molecular weight of 32kDa
      (FE-32kDa) from Gloydius blomhoffii siniticus showed a fibrin hydrolysis zone at
      the concentration of 0.2 mg/mL in the fibrin plate assay. The fibrin hydrolysis
      activity of the enzyme was inhibited completely by ethylenediaminetetraacetic
      acid (EDTA), ethyleneglycoltetraacetic acid (EGTA), and 1, 10-phenanthroline,
      thiothreitol and cysteine, and partially by phenylmethanesulfonylfluoride (PMSF).
      Metal ions such as Fe(2+) and Hg(2+) inhibited the fibrin hydrolysis completely,
      but Zn(2+) enhanced it. FE-32kDa hydrolyzed alpha-chain but did not hydrolyze
      beta-chain and gamma-chain of fibrinogen. High-molecular-weight polypeptides of
      gelatin were hydrolyzed partially into low-molecular-weight polypeptides, but the
      extent of hydrolysis was limited. FE-32kDa induced hemorrhage beneath back skin
      of mice at the dose of 2 MUg. CONCLUSIONS: FE-32kDa is a alpha-fibrin(ogen)olytic
      metalloprotease that requires Zn(2+) for fibrinolytic activity and causes
      hemorrhage, suggesting that the enzyme is not appropriate for use as a clinical
      pharmacopuncture.

PMID- 25780690
TI  - Study of Single-dose Toxicity of Guseonwangdo-go Glucose Intramuscular Injection
      in Sprague-Dawley Rats.
AB  - OBJECTIVES: This study was performed to analyze single-dose intramuscular
      toxicity of Guseonwangdo-go glucose pharmacopuncture. METHODS: Eighty six-week
      old Sprague-Dawley rats were divided into two large groups of forty rats;
      Guseonwangdo-go glucose 5% and Guseonwangdo-go glucose 20% groups. Each group was
      sub-divided into four smaller groups of five males and five females, with the
      following dosages of pharmacopuncture being administered by intramuscular (IM)
      injection in each group: group 1 (G1, control group): 1.0 mL of normal saline
      solution, group 2 (G2, low-dose group): 0.1 mL, group 3 (G3, mid-dose group): 0.5
      mL, and group 4 (G4, high-dose group): 1.0 mL. RESULTS: No mortalities or
      clinical signs were observed in any group. Also, no significant changes in body
      weights or in hematological/biochemical analyses were observed between the
      control and the experimental groups during necropsy or histopathology.
      CONCLUSION: The above findings suggest that the lethal dose of Guseonwangdo-go
      glucose 5% and 20% pharmacopuncture administered via IM injection is more than
      1.0 mL per animal in both male and female rats. Further studies on the repeated
      dose toxicity of Guseonwangdo-go glucose should be conducted to yield more
      concrete data.

PMID- 25780691
TI  - Relative Apoptosis-inducing Potential of Homeopa-thic Condurango 6C and 30C in
      H460 Lung Cancer Cells In vitro: -Apoptosis-induction by homeopathic Condurango
      in H460 cells.
AB  - OBJECTIVES: In homeopathy, it is claimed that more homeopathically-diluted
      potencies render more protective/curative effects against any disease condition.
      Potentized forms of Condurango are used successfully to treat digestive problems,
      as well as esophageal and stomach cancers. However, the comparative efficacies of
      Condurango 6C and 30C, one diluted below and one above Avogadro's limit (lacking
      original drug molecule), respectively, have not been critically analyzed for
      their cell-killing (apoptosis) efficacy against lung cancer cells in vitro, and
      signalling cascades have not been studied. Hence, the present study was
      undertaken. METHODS: 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenylte-trazolium
      bromide (MTT) assays were conducted on H460-non-small-cell lung cancer (NSCLC)
      cells by using a succussed ethyl alcohol vehicle (placebo) as a control. Studies
      on cellular morphology, cell cycle regulation, generation of reactive oxygen
      species (ROS), changes in mitochondrial membrane potential (MMP), and DNA-damage
      were made, and expressions of related signaling markers were studied. The
      observations were done in a "blinded" manner. RESULTS: Both Condurango 6C and 30C
      induced apoptosis via cell cycle arrest at subG0/G1 and altered expressions of
      certain apoptotic markers significantly in H460 cells. The drugs induced
      oxidative stress through ROS elevation and MMP depolarization at 18-24 hours.
      These events presumably activated a caspase-3-mediated signalling cascade, as
      evidenced by reverse transcriptase- polymerase chain reaction (RT-PCR), western
      blot and immunofluorescence studies at a late phase (48 hours) in which cells
      were pushed towards apoptosis. CONCLUSION: Condurango 30C had greater apoptotic
      effect than Condurango 6C as claimed in the homeopathic doctrine.

PMID- 25780692
TI  - Assessment of Factors Associated with the Safety Depth of GV15 Yamen: Factors
      Associated with the Safety Depth of GV15.
AB  - OBJECTIVES: Yamen is the fifteenth acupoint of the Governor Vessel Meridian
      (GV15). It is anatomically close to the medulla oblongata, so finding the safety
      depth of the acupoint is very important. However, few studies on the safety depth
      of GV15 have been done. METHODS: This study tried to measure the safety depth of
      GV15 by using magnetic resonance imaging (MRI) scans and to analyze the factors
      affecting the safety depth through multiple regression analyses. This study was
      carried out for patients who had a brain MRI scan while visiting Jeonju Wonkwang
      Hospital, Korea. The shortest distance between the glabella and the occipital
      protuberance (DGO), the horizontal distance between the glabella and the back of
      the head (DGB) and the dangerous depth (DD) were measured from the sagittal views
      of the MRI images. The DD is the horizontal distance from the skin's surface at
      GV15 to the spinal dura mater. RESULTS: The model suggested that the safety depth
      (SD) was significantly associated with gender (beta= 0.474, P< 0.0001), DGO
      (beta= 0.272, P= 0.027), and BMI (beta= 0.249, P= 0.005) and the combination of
      three variables can explain the SD, with R(2)= 0.571 (Table3). A longer SD was
      associated with males and with greater BMI and DGO. CONCLUSION: This study
      suggests that gender, BMI and DGO may be important factors when the SD of GV15 is
      considered clinically through a multiple regression analysis of GV15.

PMID- 25780693
TI  - Analgesic Effects of Toad Cake and Toad-cake-containing Herbal Drugs: Analgesic
      effects of toad cake.
AB  - OBJECTIVES: This study was conducted to clarify the analgesic effect of toad cake
      and toad-cake-containing herbal drugs. METHODS: We counted the writhing response
      of mice after the intraperitoneal administration of acetic acid as a nociceptive
      pain model and the withdrawal response after the plantar surface stimulation of
      the hind paw induced by partial sciatic nerve ligation of the mice as a
      neuropathic pain model to investigate the analgesic effect of toad cake and toad
      cake-containing herbal drugs. A co-treatment study with serotonin biosynthesis
      inhibitory drug 4-chloro- DL-phenylalanine methyl ester hydrochloride (PCPA), the
      catecholamine biosynthesis inhibitory drug alpha-methyl- DL-tyrosine methyl ester
      hydrochloride (AMPT) or the opioid receptor antagonist naloxone hydrochloride was
      also conducted. RESULTS: Analgesic effects in a mouse model of nociceptive pain
      and neuropathic pain were shown by oral administration of toad cake and toad-cake
      containing herbal drugs. The effects of toad cake and toad-cake-containing herbal
      drugs disappeared upon co-treatment with PCPA, but not with AMPT or naloxone in
      the nociceptive pain model; the analgesic effect of toad-cake-containing herbal
      drugs also disappeared upon co-treatment with PCPA in the neuropathic pain model.
      CONCLUSION: Toad cake and toad-cake-containing herbal drugs have potential for
      the treatments of nociceptive pain and of neuropathic pain, such as post-herpetic
      neuralgia, trigeminal neuralgia, diabetic neuralgia, and postoperative or
      posttraumatic pain, by activation of the central serotonin nervous system.

PMID- 25780694
TI  - Ethanolic Extract of Marsdenia condurango Ameliorates Benzo[a]pyrene-induced Lung
      Cancer of Rats: Condurango Ameliorates BaP-induced Lung Cancer in Rats.
AB  - OBJECTIVES: Condurango is widely used in various systems of complementary and
      alternative medicines (CAM) against oesophageal and stomach ailments including
      certain types of cancer. However, until now no systematic study has been
      conducted to verify its efficacy and dose with proper experimental support.
      Therefore, we examined if ethanolic extract of Condurango could ameliorate
      benzo[a]pyrene (BaP)-induced lung cancer in rats, in vivo to validate its use as
      traditional medicine. METHODS: Fifteen male and 15 female Sprague-Dawley (SD)
      rats were treated with 0.28 mg/kg of Sweet Bee Venom (SBV) (high-dosage group)
      and the same numbers of male and female SD rats were treated with 0.2 mL/kg of
      normal saline (control group) for 13 weeks. We selected five male and five female
      SD rats from the high-dosage group and the same numbers of male and female SD
      rats from the control group, and we observed these rats for four weeks. We
      conducted body-weight measurements, ophthalmic examinations, urinalyses and
      hematology, biochemistry, histology tests. RESULTS: A histological study revealed
      gradual progress in lung tissue-repair activity in Condurango-fed cancer-bearing
      rats, showing gradual tissue recovery after three months of drug administration.
      Condurango has the capacity to generate reactive oxygen species (ROS), which may
      contribute to a reduction in anti-oxidative activity and to an induction of
      oxidative stress-mediated cancer cell-death. Condurango-activated pro-apoptotic
      genes (Bax, caspase-3, caspase-9, p53, cytochrome-c, apaf-1, ICAD and PARP) and
      down-regulated antiapoptotic-Bcl-2 expression were noted both at mRNA and protein
      levels. Studies on caspase-3 activation and PARP cleavage by western blot
      analysis revealed that Condurango induced apoptosis through a caspase-3-dependent
      pathway. CONCLUSION: The anticancer efficacy of an ethanolic extract of
      Condurango for treating BaP-induced lung cancer in rats lends support for its use
      in various traditional systems of medicine.

PMID- 25780695
TI  - Study on a 4-week recovery test of sweet bee venom after a 13-week, repeated,
      intramuscular dose toxicity test in sprague-dawley rats.
AB  - OBJECTIVES: This study was performed to check for reversibility in the changes
      induced by a 13-week, repeated, dose toxicity test of Sweet Bee Venom (SBV) in
      Sprague-Dawley (SD) rats. METHODS: Fifteen male and 15 female SD rats were
      treated with 0.28 mg/kg of SBV (high-dosage group) and the same numbers of male
      and female SD rats were treated with 0.2 mL/kg of normal saline (control group)
      for 13 weeks. We selected five male and five female SD rats from the high-dosage
      group and the same numbers of male and female SD rats from the control group, and
      we observed these rats for four weeks. We conducted body-weight measurements,
      ophthalmic examinations, urinalyses and hematology, biochemistry, histology
      tests. RESULTS: (1) Hyperemia and movement disorder were observed in the 13-week,
      repeated, dose toxicity test, but these symptoms were not observed during the
      recovery period. (2) The rats in the high-dose group showed no significant
      changes in weight compared to the control group. (3) No significant differences
      in the ophthalmic parameters, urine analyses, complete blood cell counts (CBCs),
      and biochemistry were observed among the recovery groups. (4) No changes in organ
      weights were observed during the recovery period. (5) Histological examination of
      the thigh muscle indicated cell infiltration, inflammation, degeneration,
      necrosis of muscle fiber, and fibrosis during the treatment period, but these
      changes were not observed during the recovery period. The fatty liver change that
      was observed during the toxicity test was not observed during the recovery
      period. No other organ abnormalities were observed. CONCLUSION: The changes that
      occurred during the 13-week, repeated, dose toxicity test are reversible, and SBV
      can be safely used as a treatment modality.

PMID- 25780696
TI  - Effects of Sumsu (Bufonis venenum) Pharmacopuncture Treatment on Depression in
      Mice.
AB  - OBJECTIVES: The main objective of this study was to evaluate the anti-depressant
      effects of pharmacopuncture using sumsu (Bufonis venenum). METHODS: Animals were
      divided into three groups (control, sham, and experimental), with eight mice per
      group. The sham and the experimental groups were exposed to 2 hours of
      immobilization stress daily for 14 days. They were also injected with normal
      saline (sham) or subjected to pharmacopuncture with sumsu at the acupoints HT7,
      SP6, and GV20 (experimental). The depression or anxiety-like behaviors of the
      mice in each group were evaluated 1 day after treatment. RESULTS: There was no
      difference in locomotor activity between the groups during the open-field test;
      i.e., all groups had normal motor function. However, the open-field and the
      forced-swimming tests revealed that depression and anxiety-like behaviors were
      decreased significantly in the group treated with sumsu pharmacopuncture.
      CONCLUSION: Sumsu pharmacopuncture attenuated depressive or anxiety-like behavior
      in mice stressed with chronic immobilization. These results suggest that sumsu
      pharmacopuncture has therapeutic potential for treating neuropsychiatric
      disorders such as anxiety or depression disorder.

PMID- 25780697
TI  - Physiological Role of a Multigrain Diet in Metabolic Regulations of Lipid and
      Antioxidant Profiles in Hypercholesteremic Rats: Multigrain diet in hyperlipemia.
AB  - OBJECTIVES: The objective of the present study was to investigate the lipid and
      the antioxidant regulatory potential of a multigrain diet in laboratory animals
      with reference to lipid profiles, tissue lipid peroxidation and antioxidant
      status. METHODS: Two types of diets, with or without addition of cholesterol,
      were used in the study - a commercial diet and a formulated multigrain diet (with
      Sorghum vulgare, Avena sativa, Pennisetum typhoideum, Oryza sativa, Eleusine
      coracana and Zea mays grains). After a 10-week period of feeding the diets to
      albino rats the plasma, liver and fecal lipid profiles and the hepatic and renal
      antioxidant status of the animals that were fed the commercial and the formulated
      diets (with and without cholesterol addition) were assessed. RESULTS: The
      commercial diet supplemented with cholesterol elevated the levels of plasma total
      lipids, total cholesterol, triglycerides, low-density lipoprotein cholesterol
      (LDL-C), and very low-density lipoprotein cholesterol (VLDL-C), as well as the
      atherogenic index (AI). The high-density lipoprotein cholesterol (HDL-C) content
      and the antioxidant profiles (total ascorbic acid, superoxide dismutase,
      catalase, glutathione peroxidase reduced glutathione) declined along with
      increases in lipid peroxidation. The formulated diet (with and without addition
      of cholesterol) was found to be more efficient than the commercial diet in
      controlling plasma, hepatic and fecal lipid profiles, as well as hepatic and
      renal lipid peroxidation and antioxidant status, than of the hypercholesteremic
      animals. CONCLUSION: The multigrain diet used in the present study is effective
      in countering the hyperlipidemia and oxidative stress caused by high cholesterol
      intake.

PMID- 25780698
TI  - Single-dose Intramuscular Toxicity of Neutral Natured Blood Stasis
      Pharmacopuncture in Sprague-Dawley Rats.
AB  - OBJECTIVES: This study was performed to analyze the single-dose toxicity of
      neutral natured blood stasis pharmacopuncture extracts. METHODS: All experiments
      were conducted at Biotoxtech, an institution authorized to perform non-clinical
      studies, under the regulations of Good Laboratory Practice (GLP). Sprague-Dawley
      rats were chosen for the pilot study. Doses of neutral natured blood stasis
      pharmacopuncture extracts, 0.1, 0.5 and 1.0 mL, were administered to the
      experimental group, and the same doses of normal saline solution were
      administered to the control group. This study was conducted under the approval of
      the Institutional Animal Ethics Committee. RESULTS: In all 4 groups, no deaths
      occurred, and the neutral natured blood stasis pharmacopuncture extracts
      administered by intramuscular (IM) injection was over 1.0 mL/animal. No
      significant changes in the body weights between the control group and the
      experimental group were observed. To check for abnormalities in organs and
      tissues, we used microscopy to examine representative histological sections of
      each specified organ; the results showed no significant differences in any organs
      or tissues. CONCLUSION: The above findings suggest that treatment with neutral
      natured blood stasis pharmacopuncture extracts is relatively safe. Further
      studies on this subject should be conducted to yield more concrete evidence.

PMID- 25780699
TI  - Single Intramuscular-dose Toxicity of Samgihwalryeok-Pharmacopuncture in Sprague
      Dawley Rats.
AB  - OBJECTIVES: This study was performed to examine the single-dose toxicity of
      Samgihwalryeok pharmacopuncture. METHODS: Forty six-week-old Sprague-Dawley (SD)
      rats were divided into four groups of 10 rats each; each group was then sub
      divided into two smaller groups, one of five males and the other of five females.
      Group 1 (G1, control) received 1.0 mL of normal saline solution, while group 2
      (G2, low-dose group), group 3 (G3, mid-does group, and group 4 (G4, high-dose
      group) received 0.1, 0.5, and 1.0 mL of Samgihwalryeok pharmacopuncture,
      respectively. RESULTS: No mortalities or clinical signs were observed in the four
      groups. Also, no significant changes in body weights were observed among the
      group, and no significant differences in hematology/biochemistry, necropsy, or
      histopathology results were noted. CONCLUSION: The above findings suggest that
      treatment with Samgihwalryeok pharmacopuncture is relatively safe. Further
      studies on this subject are needed.

PMID- 25780700
TI  - A Pilot Study on Single-dose Toxicity Testing of Scolopendrid Pharmacopuncture in
      Sprague-Dawley Rats.
AB  - OBJECTIVES: This study was performed to analyze single dose toxicity and the
      lethal dose of Scolopendrid Pharmacopuncture in rats. METHODS: All experiments
      were conducted at the Korea Testing & Research Institute (KTR), an institution
      authorized to perform non-clinical studies, under the regulations of Good
      Laboratory Practice (GLP). Sprague-Dawley rats were chosen for the pilot study.
      Doses of Scolopendrid pharmacopuncture, 0.1, 0.5, and 1.0 mL, were administered
      to the experimental group, and 1.0 mL doses of normal saline solution were
      administered to the control group. This study was conducted under the approval of
      the Institutional Animal Ethic Committee. RESULTS: No deaths or abnormalities
      occurred in any of the groups. No significant changes in the weight,
      hematological parameters or clinical chemistry were noted between the control
      group and the experimental group. To check for abnormalities in organs and
      tissues, we used microscopy to examine representative histological sections of
      each specified organ; the results showed no significant differences in any of the
      organs or tissues. CONCLUSION: The above findings suggest Scolopendrid
      Pharmacopuncture is a relatively safe to use for treatment. Further studies on
      the subject should be conducted to yield more concrete evidence.

PMID- 25780701
TI  - Intravenous injection of saeng maek san - a safe method of treatment in rats.
AB  - OBJECTIVES: This study evaluated the single-dose toxicity of Saeng Maek San (SMS)
      in rats. METHODS: All experiments were conducted at Biotoxtech (Chungwon, Korea),
      an institute authorized to perform non-clinical studies under the regulations of
      Good Laboratory Practice (GLP). A single-dose intravenous toxicity study was
      carried out on 40 6-week-old Sprague-Daley rats. The animals were randomly
      divided into the following four groups of ten animals each: Group 1 (G1) was the
      control group, with each animal receiving an intravenous injection of 1.0 mL of
      saline, and Groups 2, 3 and 4 (G2, G3 and G4) were the experimental groups, with
      the animals in the groups receiving an injection of 0.1, 0.5 and 1.0 mL of SMS,
      respectively. Mortality, clinical signs, body-weight changes and gross
      pathological findings were observed for 14 days following a single administration
      of SMS or saline. Organ weights, clinical chemistry and hematology were analyzed
      at 14 days. This study was conducted with the approval of the Institutional
      Animal Ethics Committee. RESULTS: No deaths occurred in any of the four
      groups,indicating that the lethal dose of SMS in rats is greater than 1.0
      mL/animal. Some changes in weights of male rats between the control group and the
      experimental groups were observed, but no significant changes in the weights of
      female rats were noted. To identify abnormalities in organs and tissues, we
      stained representative sections of each specified organ with hematoxylin and
      eosin for examination with a light microscope. No significant abnormalities were
      observed in any of the organs or tissues. CONCLUSION: The results suggest that
      intravenous injection of SMS is a safe method of treatment.

PMID- 25780702
TI  - Study of a 13-weeks, Repeated, Intramuscular Dose, Toxicity Test of Sweet Bee
      Venom in Sprague-Dawley Rats.
AB  - OBJECTIVES: This study was performed to analyze a 13-week repeated dose toxicity
      test of Sweet Bee Venom (SBV) extracted from bee venom and administered in
      Sprague-Dawley (SD) rats. METHODS: Male and female 5-week-old SD rats were
      treated once daily with SBV (high-dosage group: 0.28 mg/kg; medium-dosage group:
      0.14 mg/kg; or low-dosage group: 0.07 mg/kg) for 13 weeks. Normal saline was
      administered to the control group in a similar manner (0.2 mL/kg). We conducted
      clinical observations, body weight measurements, ophthalmic examinations,
      urinalyses, hematology and biochemistry tests, and histological observations
      using hematoxylin and eosin (H&E) staining to identify any abnormalities caused
      by the SBV treatment. RESULTS: During this study, no mortality was observed in
      any of the experimental groups. Hyperemia and a movement disorder were observed
      around the area of in all groups that received SBV treatment, with a higher
      occurrence in rats treated with a higher dosage. Male rats receiving in the high
      dosage group showed a significant decrease in weight during the treatment period.
      Compared to the control group, no significant changes in the ophthalmic
      parameters, the urine analyses, the complete blood cell count (CBC), and the
      biochemistry in the groups treated with SBV. Compared to the control group, some
      changes in organ weights were observed in the medium-and the high-dosage groups,
      but the low-dosage group showed no significant changes. Histological examination
      of thigh muscle indicated cell infiltration, inflammation, degeneration, and
      necrosis of muscle fiber, as well as fibrosis, in both the medium- and the high
      dosage groups. Fatty liver change was observed in the periportal area of rats
      receiving medium and high dosages of SBV. No other organ abnormalities were
      observed. CONCLUSION: Our findings suggest that the No Observed Adverse Effect
      Level (NOAEL) of SBV is approximately 0.07 mg/kg in male and female SD rats.

PMID- 25780703
TI  - Kaposi's Varicelliform Eruption in Atopic Dermatitis treated with Korean
      medicine.
AB  - OBJECTIVES: This case report is to present a complete recovery from Kaposi's
      varicelliform eruption (KVE) that occurred in a patient with atopic dermatitis by
      applying Korean Medicine therapies. METHODS: Hwangyeonhaedoktang pharmacopuncture
      (HP), 0.3 mL, and 25% bee venom pharmacopuncture (BVP), 0.1 mL, were injected,
      0.2 mL each, at both BL13 acupoints once a day in the morning. Acupuncture was
      applied at Sama Upper, Middle and Lower of the Master Tung acupuncture points and
      at ST44 on the left lateral for 30 minutes twice a day. The affected face was
      gauze dressed with mixture of 2.0 mL HP and 1.0 mL 25% BVP with 20 mL of normal
      saline twice a day. Herbal Medicine, Seungmagalgeuntang, was administered three
      times a day after each meal. RESULTS: Rashes and papules on the face were
      completely cleared after 10 days of treatments. CONCLUSION: KVE, an acute and
      urgent dermatitis, can be effectively treated with Korean medicine.

PMID- 25780704
TI  - Biological Parameters for Evaluating the Toxic Potency of Petroleum Ether Extract
      of Wattakaka volubilis in Wistar Female Rats.
AB  - OBJECTIVES: The present study investigated the toxic properties of petroleum
      ether extract of Wattakaka (W.) volubilis in Wistar female rats. METHODS: An in
      vitro brine shrimp lethality bioassay was studied in A. Salina nauplii, and the
      lethality concentrations were assessed for petroleum ether extract of W.
      volubilis. A water soluble portion of the test extract was used in different
      concentrations from 100-1000 MUg/mL of 1 mg/mL stock solution. A 24-hours
      incubation with a 1-mL aliquot in 50 mL of aerated sea water was considered to
      calculate the percentage rate of dead nauplii with test extract administration
      against a potassium-dichromate positive control. The acute and the sub-acute
      toxicities of petroleum ether extract of W. volubilis were evaluated orally by
      using gavage in female Wistar rats. Food and water intake, body weight, general
      behavioral changes and mortality of animals were noted. Toxicity or death was
      evaluated following the administration of petroleum ether extract for 28
      consecutive days in the female rats. Serum biochemical parameters, such as
      alanine aminotransferase (ALT), alkaline phosphatase (ALP), bilirubin, total
      cholesterol, triglyceride, total protein, glucose, urea, creatinine, sodium,
      potassium and alpha-amylase levels, were measured in the toxicity evaluations.
      Pathological changes in isolated organs, such as the liver, kidneys, and
      pancreas, were also examined using hematoxylin and eosin dye fixation after the
      end of the test extract's administration. RESULTS: The results of the brine
      shrimp assay indicate that the evaluated concentrations of petroleum ether
      extract of W. volubilis were found to be non-toxic. In the acute and the sub
      acute toxicity evaluations, no significant differences were observed between the
      control animals and the animals treated with extract of W. volubilis. No abnormal
      histological changes were observed in any of the animal groups treated with
      petroleum ether extract of W. volubilis. CONCLUSION: These results suggest that
      petroleum ether extract of W. volubilis has a non-toxic effect in Wistar female
      rats.

PMID- 25780705
TI  - Hepatoprotective Evaluation of Ganoderma lucidum Pharmacopuncture: In vivo
      Studies of Ethanol-induced Acute Liver Injury.
AB  - OBJECTIVES: Alcohol abuse is a public issue and one of the major causes of liver
      disease worldwide. This study was aimed at investigating the protective effect of
      Ganoderma lucidum pharmacopuncture (GLP) against hepatotoxicity induced by acute
      ethanol (EtOH) intoxication in rats. METHODS: Sprague-Dawley (SD) rats were
      divided into 4 groups of 8 animals each: normal, control, normal saline
      pharmacopuncture (NP) and GLP groups. The control, NP and GLP groups received
      ethanol orally. The NP and the GLP groups were treated daily with injections of
      normal saline and Ganoderma lucidum extract, respectively. The control group
      received no treatment. The rats in all groups, except the normal group, were
      intoxicated for 6 hours by oral administration of EtOH (6 g/kg BW). The same
      volume of distilled water was administered to the rats in the normal group. Two
      local acupoints were used: Qimen (LR14) and Taechung (LR3). A histopathological
      analysis was performed, and the liver function and the activities of antioxidant
      enzymes were assessed. RESULTS: GLP treatment reduced the histological changes
      due to acute liver injury induced by EtOH and significantly reduced the increase
      in the alanine aminotransferase (ALT) enzyme; however, it had an insignificant
      effect in reducing the increase in aspartate aminotransferase (AST) enzyme. It
      also significantly ameliorated the superoxide dismutase (SOD) and the catalase
      (CAT) activities. CONCLUSION: The present study suggests that GLP treatment is
      effective in protecting against ethanol-induced acute hepatic injury in SD rats
      by modulating the activities of ethanol-metabolizing enzymes and by attenuating
      oxidative stress.

PMID- 25780706
TI  - Single-dose Toxicity of Guseonwangdo-go Glucose 20% Intravenous Injection in
      Sprague-Dawley Rats.
AB  - OBJECTIVES: This study was performed to evaluate the single-dose intravenous
      toxicity of Guseonwangdo-go glucose 20% pharmacopuncture. METHODS: Forty Sprague
      Dawley rats were divided into four groups of five males and five females per
      group: an intravenous (IV) injection of 1.0 mL of normal saline solution per
      animal was administered to group 1 (G1, control group); an IV injections of 0.1,
      0.5, and 1.0 mL of Guseonwangdo-go glucose pharmacopuncture per animal were
      administered to experimental groups 2, 3, and 4 (G2, G3, and G4), respectively.
      General symptoms, body weights, hematological and biochemical test results, and
      necropsy histopathological observation were recorded in all groups. In the
      statistical analyses, significance was determined by using the one-way analysis
      of variance (ANOVA). The significance level was 0.05 in all comparisons. RESULTS:
      For 14 days, no deaths or abnormalities were observed in any of the 4 groups. The
      body weights of all groups continuously increased during the observation period.
      In the hematological test, the WBC count was significantly increased in female
      rats of G4 compared to the control group, but this difference was considered not
      to be statistically meaningful. No significant biochemical changes were observed.
      On necropsy, crust formation was observed in one rat of the control group, and
      granulation tissues were observed around the injection site in one rat of G4;
      these changes were concluded to have been caused by injection of the needle into
      a vein. CONCLUSION: The findings suggest that the lethal dose of Guseonwangdo-go
      glucose pharmacopuncture is more than 1.0 mL per animal in both male and female
      rats. Thus, we can conclude that Guseonwangdo-go glucose pharmacopuncture
      injection is relatively safe to use in acute toxicity tests. Further studies are
      needed to establish more detailed evidences of its toxicity.

PMID- 25780707
TI  - Single Intravenous-dose Toxicity of Water-soluble Carthami-flos Pharmacopuncture
      (WCF) in Rats.
AB  - OBJECTIVES: This study was performed to analyze the toxicity and to find the
      lethal dose of the test substance Water-soluble Carthami-flos pharmacopuncture
      (WCF) when used as a single intravenous-dose in 6-week-old, male and female
      Sprague-Dawley rats. METHODS: The experiment was conducted at Biotoxtech
      according to Good Laboratory Practices. 20 female and 20 male Spague-Dawley rats
      were divided into 4 groups of 5 female and 5 male animals per group. The rats in
      the three experimental groups received single intravenous injections with 0.125
      mL, 0.25-mL and 0.5-mL/animal doses of WCF, Groups 2, 3, and 4, respectively, and
      the control group, Group 1, received a single intravenous injection with a 0.5-mL
      dose of normal saline. Clinical signs were observed and body weight measurements
      were carried out for 14 days following the injections. At the end of the
      observation period, hematology, clinical chemistry, histopathological tests and
      necropsy were performed on the injected parts. RESULTS: No deaths occurred in any
      of the groups. Also, no significant changes in body weight, hematological
      parameters or clinical chemistry test results between the control group and the
      experimental groups were observed. Visual inspection after necropsy showed no
      abnormalities. Histopathological tests on the injected parts showed no
      significant differences, except for Group 1 females; however, the result was
      spontaneous generation and had no toxicological meaning because it was not dose
      dependent. Therefore, this study showed that WCF had no effect on the injected
      parts in terms of clinical signs, body weight, hematology, clinical chemistry,
      and necropsy. CONCLUSION: As a result of single intravenous-dose tests of the
      test substance WCF in 4 groups of rats, the lethal dose for both males and
      females exceeded 0.5 mL/animal. Therefore, WCF is a relatively safe
      pharmacopuncture that can be used for treatment, but further studies should be
      performed.

PMID- 25780708
TI  - Ganoderma lucidum Pharmacopuncture for the Treatment of Acute Gastric Ulcers in
      Rats.
AB  - OBJECTIVES: The gastric ulcer is a common disorder of the stomach and duodenum.
      The basic physiopathology of a gastric ulcer results from an imbalance between
      some endogenous aggressive and cytoprotective factors. This study examined
      whether Ganoderma lucidum pharmacopuncture (GLP) would provide protection against
      acute gastric ulcers in rats. METHODS: Sprague-Dawley rats were divided randomly
      into 4 groups of 8 rats each: normal, control, normal saline (NP) and GLP groups.
      The experimental acute gastric ulcer was induced by using an EtOH/HCl solution
      and the normal group received the same amount of normal saline instead of
      ethanol. The NP and the GLP groups were treated once with injections of saline
      and GLP, respectively. Two local acupoints were used: CV12 () which is the alarm
      point of the Stomach Meridian, and ST36 (), which is the sea point of the Stomach
      Meridian. The stomachs from the rats in each group were collected and analyzed
      for gross appearance and histology. Also, immunohistochemistry staining for BAX,
      Bcl-2 and TGF-beta1 was performed. RESULTS: Histological observations of the
      gastric lesions in the control group showed comparatively extensive damage of the
      gastric mucosa and necrotic lesions had penetrated deeply into the mucosa. The
      lesions were long, hemorrhagic, and confined to the glandular portions. The
      lesions were measured microscopically by using the clear depth of penetration
      into the gastric mucosal surface. The length and the width of the ulcer were
      measured and the inhibition percentage was calculated. Wound healing of the acute
      gastric ulcer was promoted by using GLP, and significant alterations of indices
      in gastric mucosa were observed. Such protection was shown by gross appearance,
      histology and immunohistochemistry staining for BAX, Bcl-2 and TGF-beta1.
      CONCLUSION: These results suggest that GLP administered at CV12 and ST36 can
      provide significant protection to the gastric mucosa against an ethanol-induced
      acute gastric ulcer.

PMID- 25780710
TI  - Objective and subjective voice examination in korean medicine.
AB  - OBJECTIVES: When a person speaks, voice problems usually include pain or
      discomfort and/or difficulties in terms of the pitch, the loudness and the
      quality of the voice. When patients with voice problems induced by stroke,
      Parkinson's disease, and systemic diseases involving the voice are examined,
      generally, of the Four Diagnoses (), a Diagnosis of Hearing can be used in
      current Korean medicine. The effects of acupuncture and herb medicine on voice
      problems have been reported for over 20 years. However, when it comes to
      improvements, objective and subjective evaluation methods need to be explained.
      METHODS: Subjective methods for evaluating voice were studied through a
      literature search of old medicinal books containing Korean medicine diagnostics,
      and an objective evaluation method using Praat software is presented. RESULTS:
      Korean medicine doctors analyze the patient's voice in clinical settings
      unconsciously on a daily basis. However, most voice diagnoses depend on the
      doctor's subjective evaluation. Voice qualities can be evaluated by using the
      Eight Principles (), including Yin-Yang; the Five Elements (Phases); the Grade,
      Roughness, Breathy, Asthenic, Strained (GRBAS) score, and the Visual Analogue
      Scale (VAS) as subjective methods, and an acoustic analysis using the Praat
      program can be used as an objective method. CONCLUSION: A more complete voice
      examination can be achieved by using subjective and objective methods at the same
      time. For an objective explanation and management of patient's voice problems or
      systemic disorders, an objective method should be used in Korean medicine, which
      already has many subjective diagnostic methods. More research needs to be
      conducted, and more clinical evidence needs to be collected in the future.

PMID- 25780709
TI  - Intravenous Single-dose Toxicity of Mountain Ginseng Pharmacopuncture in Sprague
      Dawley Rats.
AB  - OBJECTIVES: Mountain ginseng pharmacopuncture (MGP) is an extract distilled from
      either mountain cultivated ginseng or mountain wild ginseng. This is the first
      intravenous injection of pharmacopuncture in Korea. The word intravenous does not
      discriminate between arteries, veins, and capillaries in Oriental Medicine, but
      only the vein is used for MGP. The aim of this study is to evaluate the
      intravenous injection toxicity of MGP through a single-dose test in Sprague
      Dawley (SD) rats. METHODS: Male and female 6-week-old SD rats were injected
      intravenously with MGP (high dosage of 20 mL/kg or low dosage of 10 mL/kg).
      Normal saline was injected into the rats in the control group by using the same
      method. After the rats has treated, we conducted clinical observations, body
      weight measurements and histological observations. RESULTS: In this study, no
      mortalities were observed in any of the experimental groups. Also, no significant
      changes by the intravenous injection of MGP were observed in the body weights, or
      the histological observations in any of the experimental groups compared to the
      control group. The lethal dose for intravenous injection of MGP was found to be
      over 20 mL/kg in SD rats. CONCLUSION: Considering that the dosage of MGP
      generally used each time in clinical practice is about 0.3 mL/kg, we concluded
      with confidence that MGP is safe pharmacopuncture.

PMID- 25780711
TI  - Cancer pain control for advanced cancer patients by using autonomic nerve
      pharmacopuncture.
AB  - OBJECTIVES: The purpose of this study is to report a case series of advanced
      cancer patients whose cancer pain was relieved by using autonomic nerve
      pharmacopuncture (ANP) treatment. ANP is a subcutaneous injection therapy of
      mountain ginseng pharmacopuncture (MGP) along the acupoints on the spine (Hua-Tuo
      Jia-Ji-Xue; 0.5 cun lateral to the lower border of the spinous processes of
      vertebrae) to enhance the immune system and to balance autonomic nerve function.
      METHODS: Patients with three different types of cancer (gastric cancer, lung
      cancer, colon cancer with distant metastases) with cancer pain were treated with
      ANP. 1 mL of MGP was injected into the bilateral Hua-Tuo-Jia-Ji-Xue on the T1-L5
      sites (total 12 ? 20 mL injection) of each patient's dorsum by using the
      principle of symptom differentiation. During ANP treatment, the visual analogue
      scale (VAS) for pain was used to assess their levels of cancer pain; also, the
      dosage and the frequency of analgesic use were measured. RESULTS: The cancer pain
      levels of all three patients improved with treatment using ANP. The VAS scores of
      the three patients decreased as the treatment progressed. The dosage and the
      frequency of analgesics also gradually decreased during the treatment period.
      Significantly, no related adverse events were found. CONCLUSION: ANP has shown
      benefit in controlling cancer pain for the three different types of cancer
      investigated in this study and in reducing the dosage and the frequency of
      analgesics. ANP is expected to be beneficial for reducing cancer pain and, thus,
      to be a promising new treatment for cancer pain.

PMID- 25780712
TI  - Sweet Bee Venom Pharmacopuncture May be Effective for Treating Sexual
      Dysfunction.
AB  - Sexual dysfunction (SD) is a health problem which occurs during any phase of the
      sexual response cycle that keeps the individual or couple from experiencing
      satisfaction from the sexual activity. SD covers a wide variety of symptoms like
      in men, erectile dysfunction and premature or delayed ejaculation, in women,
      spasms of the vagina and pain with sexual intercourse, in both sexes, sexual
      desire and response. And pharmacopuncture, i.e. injection of subclinical doses of
      drugs, mostly herb medicine, in acupoints, has been adopted with successful
      results. This case report showed the effect of bee venom on SD. A 51-year-old
      male patient with SD, who had a past history of taking Western medication to
      treat his SD and who had previously undergone surgery on his lower back due to a
      herniated disc, received treatments using pharmacopuncture of sweet bee venom
      (SBV) at Gwanwon (CV4), Hoeeum (CV1), Sinsu (BL23), and Gihaesu (BL24) for 20
      days. Objectively, the patient showed improvement on most items on the
      International Index for Erectile Dysfunction (IIEF) like 28 to 29 out of perfect
      score 30 for erectile function, 10 to 10 out of perfect score 10 for orgasmic
      function, 6 to 8 out of perfect score 10 for sexual desire, 10 to 13 out of
      perfect score 15 for satisfaction with intercourse, and 6 to 8 out of perfect
      score 10 for overall satisfaction; subjectively, his words, the tone of his voice
      and the look of confidence in his eyes all indicated improvement. Among the
      variety of effects of SBV pharmacopuncture, urogenital problems such as SD may be
      health problems that pharmacopuncture can treat effectively. 

PMID- 25780713
TI  - Plexiform neurofibroma treated with pharmacopuncture.
AB  - OBJECTIVES: The purpose of this study is to report a case of a plexiform
      neurofibroma (PNF) in the pelvic region treated with sweet bee venom (SBV) and
      mountain ginseng pharmacopuncture (MGP). METHODS: A 16-year-old girl was
      diagnosed as having PNFs, neurofibromatosis type 1, 10 years ago and she had
      surgery three times to remove the benign tumors, but the growth of the PNFs
      continued. She has been treated in our clinic with SBV and MGP two times per
      month from March 2010 to April 2014. SBV was injected intra-subcutaneously at the
      borders of the PNFs in the pelvic region, and MGP was administrated intravenously
      each treatment time. RESULTS: The growths of the PNFs occurred rapidly and
      continued steadily before treatment. Since March 2010, she has been treated in
      our clinic, and the growths of the PNFs have almost stopped; further-more, the
      discomfort of hip joint pain has been reduced, and her general condition has
      improved. CONCLUSION: We cautiously conclude that SBV and MGP treatment has some
      effects that suppress the growth and the spread of the PNFs in this patient.

PMID- 25780714
TI  - Trend of pharmacopuncture therapy for treating cervical disease in Korea.
AB  - OBJECTIVES: The purpose of this study is to analyze trends in domestic studies on
      pharmacopuncture therapy for treating cervical disease. METHODS: This study was
      carried out on original copies and abstracts of theses listed in databases or
      published until July 2014. The search was made on the Oriental medicine Advanced
      Searching Integrated System (OASIS) the National Digital Science Library (NDSL),
      and the Korean traditional knowledge portal. Search words were 'pain on cervical
      spine', 'cervical pain', 'ruptured cervical disk', 'cervical disc disorder',
      'stiffness of the neck', 'cervical disk', 'whiplash injury', 'cervicalgia',
      'posterior cervical pain', 'neck disability', 'Herniated Nucleus Pulposus (HNP)',
      and 'Herniated Intervertebral Disc (HIVD)'. RESULTS: Twenty-five clinical theses
      related to pharmacopuncture were selected and were analyzed by year according to
      the type of pharmacopuncture used, the academic journal in which the publication
      appeared, and the effect of pharmacopuncture therapy. CONCLUSION: The significant
      conclusions are as follows: (1) Pharmacopunctures used for cervical pain were Bee
      venom pharmacopuncture, Carthami-flos pharmacopuncture, Scolopendra
      pharmacopuncture, Ouhyul pharmacopuncturen, Hwangryun pharmacopuncture, Corpus
      pharmacopuncture, Soyeom pharmacopuncture, Hwangryunhaedoktang pharmacopuncture,
      Shinbaro phamacopuncture. (2) Randomized controlled trials showed that
      pharmacopuncture therapy combined with other methods was more effective. (3) In
      the past, studies oriented toward Bee venom pharmacopuncture were actively
      pursued, but the number of studies on various other types of pharmacopuncture
      gradually began to increase. (4) For treating a patient with cervical pain, the
      type of pharmacopuncture to be used should be selected based on the cause of the
      disease and the patient's condition.

PMID- 25780715
TI  - Research on Korean Pharmacopuncture in South Korea since 2007.
AB  - OBJECTIVES: The purpose of this study was to investigate the current trends in
      research on pharmacopuncture in Korea since 2007. METHODS: A literature review
      was performed by using the search engines 'Science and Technology Society
      Village', 'Korean Studies Information Service System', 'National Discovery for
      Science Leaders', and 'Oriental Medicine Advanced Searching Integrated System' in
      Korea from January 2007 to December 2013. Searched key words were
      'pharmacopuncture', 'herbal acupuncture', 'aqua-acupuncture', and 'bee venom'.
      Finally, we selected 457 papers, including Korean experimental studies and
      clinical studies. Selected papers were classified according to year of
      publication, type of pharmacopuncture, disease & topic, research type and the
      publishing journal. RESULTS: One hundred fifty pharmacopunctures were studied in
      457 papers. Single compound pharmacopuncture was the most studied
      pharmacopuncture in experimental studies while animal-based pharmacopuncture was
      the most studied pharmacopuncture in clinical studies. Bee venom placed first
      among the various pharmacopunctures, followed by placenta, sweet bee venom,
      mountain-ginseng, and anti-inflammatory pharmacopunctures. Experimental research
      on pharmacopuncture has fallen since 2007 when 55 papers were published. However,
      clinical research has been increasing steadily. In clinical studies, case reports
      were numerous than randomized clinical trials (RCTs). Musculoskeletal diseases
      were the most frequently-treated diseases in studies on pharmacopuncture; among
      the musculoskeletal diseases, rheumatoid arthritis was the most frequently
      treated disease in experimental studies and low back pain was the most frequently
      treated condition in clinical studies. Since 2007, 45 different journals have
      published studies on pharmacopuncture, with the Journal of the Korean Acupuncture
      and Moxibustion Medicine Society having the largest number of papers on
      pharmacopuncture and the Journal of Pharmacopuncture the second largest number.
      CONCLUSION: The trends in research on pharmacopuncture published in studies from
      2007 to 2013 were similar to those in studies published before 2006. Many studies
      on pharmacopuncture focused on bee venom and musculoskeletal diseases. Additional
      studies on diverse types of and indications for pharmacopuncture are needed.

PMID- 25780716
TI  - A case study of 20 patients with lateral epicondylitis of the elbow by using
      hwachim (burning acupuncture therapy) and sweet bee venom pharmacopuncture.
AB  - OBJECTIVES: This study was performed to estimate the effectiveness of burning
      acupuncture therapy (Hwachim) and sweet bee venom pharmacopuncture (S-BV
      pharmacopuncture) in treating lateral epicondylitis of elbow. METHODS: We
      selected 33 patients at first, but 13 patients were excluded due to unclear
      medical records. Finally, a total of 20 patients who had received treatment from
      January 2012 to December 2013 were included in this study; all 20 patients had
      undergone Hwachim for the treatment of lateral epicondylitis of elbow, and 19 of
      the 20 had been treated with S-BV pharmacopuncture (Korea Pharmacopuncture
      Institute, KPI) and transcutaneous electrical nerve stimulation (TENS) as an
      ancillary treatment method. The degrees of pain of the 20 patients were evaluated
      by using the visual analogue scale (VAS) score at their first and final visits.
      The Wilcoxon signed rank test and the Kruskal-Wallis test were used to compare
      the VAS scores statistically. RESULTS: The VAS score had decreased significantly
      from 10.00 +/- 0.00 to 4.00 +/- 2.47 (P = 0.000) by the end of the treatment. No
      significant changes were observed based on the number of treatments (P = 0.246),
      the age of the patients (P = 0.810), the duration of the illness (P = 0.705), and
      the location of the lesion (P = 0.076). CONCLUSION: This study suggests Hwachim
      and S-BV pharmacopuncture are very effective for treating lateral epicondylitis
      of the elbow.

PMID- 25780717
TI  - A 4-week, repeated, intravenous dose, toxicity test of mountain ginseng
      pharmacopuncture in sprague-dawley rats.
AB  - OBJECTIVES: Mountain ginseng pharmacopuncture (MGP) is a pharmacopuncture made by
      distilling extract from mountain cultivated ginseng or mountain wild ginseng.
      This pharmacopuncture is injected intravenously, which is a quick, lossless way
      of strongly tonifying Qi function. The present study was undertaken to evaluate a
      4-week, repeated, intravenous injection, toxicity test of MGP in Sprague-Dawley
      (SD) rats. METHODS: Twenty male and female 6-week-old SD rats were used as
      subjects. We divided the SD rats into 4 groups: the high-dosage (10 mL/kg),
      medium-dosage (5 mL/kg), low-dosage (2.5 mL/kg) and control (normal saline)
      groups. MGP or normal saline was injected intravenously into the caudal vein of
      the rats once daily for 4 weeks. Clinical signs, body weights, and food
      consumption were monitored during the observation period, and hematology, serum
      biochemistry, organ weight, necropsy, and histological examinations were
      conducted once the observations had been completed. RESULTS: No mortality was
      observed in any of the groups during the observation period. No changes due to
      MGP were observed in the experimental groups regarding clinical signs, body
      weights, food consumption, hematology, serum biochemistry, organ weight and
      necropsy. No histological changes due to MGP were observed in any of the male or
      female rats in the high-dosage group. CONCLUSION: During this 4-week, repeated,
      intravenous injection, toxicity test of MGP in SD rats, no toxic changes due to
      MGP were observed in any of the male or female rats in the high-dosage group.
      Thus, we suggest that the high and the low doses in a 13-week, repeated test
      should be 10 mL/kg and 2.5 mL/kg, respectively.

PMID- 25780718
TI  - HPLC method for simultaneous quantitative detection of quercetin and curcuminoids
      in traditional chinese medicines.
AB  - OBJECTIVES: Quercetin and curcuminoids are important bioactive compounds found in
      many herbs. Previously reported high performance liquid chromatography
      ultraviolet (HPLC-UV) methods for the detection of quercetin and curcuminoids
      have several disadvantages, including unsatisfactory separation times and lack of
      validation according the standard guidelines of the International Conference on
      Harmonisation of Technical Requirements for Registration of Pharmaceuticals for
      Human Use. METHODS: A rapid, specific, reversed phase, HPLC-UV method with an
      isocratic elution of acetonitrile and 2% v/v acetic acid (40% : 60% v/v) (pH 2.6)
      at a flow rate of 1.3 mL/minutes, a column temperature of 35 degrees C, and
      ultraviolet (UV) detection at 370 nm was developed. The method was validated and
      applied to the quantification of different types of market available Chinese
      medicine extracts, pills and tablets. RESULTS: The method allowed simultaneous
      determination of quercetin, bisdemethoxycurcumin, demethoxycurcumin and curcumin
      in the concentration ranges of 0.00488 ? 200 MUg/mL, 0.625 ? 320 MUg/mL, 0.07813
      ? 320 MUg/mL and 0.03906 ? 320 MUg/mL, respectively. The limits of detection and
      quantification, respectively, were 0.00488 and 0.03906 MUg/mL for quercetin,
      0.62500 and 2.50000 MUg/mL for bisdemethoxycurcumin, 0.07813 and 0.31250 MUg/mL
      for demethoxycurcumin, and 0.03906 and 0.07813 MUg/mL for curcumin. The percent
      relative intra day standard deviation (% RSD) values were 0.432 ? 0.806 MUg/mL,
      0.576 ? 0.723 MUg/mL, 0.635 ? 0.752 MUg/mL and 0.655 ? 0.732 MUg/mL for
      quercetin, bisdemethoxycurcumin, demethoxycurcumin and curcumin, respectively,
      and those for intra day precision were 0.323 ? 0.968 MUg/mL, 0.805 ? 0.854
      MUg/mL, 0.078 ? 0.844 MUg/mL and 0.275 ? 0.829 MUg/mL, respectively. The intra
      day accuracies were 99.589% ? 100.821%, 98.588% ? 101.084%, 9.289% ? 100.88%, and
      98.292% ? 101.022% for quercetin, bisdemethoxycurcumin, demethoxycurcumin and
      curcumin, respectively, and the inter day accuracy were 99.665% ? 103.06%,
      97.669% ? 103.513%, 99.569% ? 103.617%, and 97.929% ? 103.606%, respectively.
      CONCLUSION: The method was found to be simple, accurate and precise and is
      recommended for routine quality control analysis of commercial Chinese medicine
      products containing the flour flavonoids as their principle components in the
      extracts.

PMID- 25780719
TI  - Infrared thermal imaging in patients with medial collateral ligament injury of
      the knee - a retrospective study.
AB  - OBJECTIVES: Digital infrared thermographic imaging (DITI) has been used widely
      for various inflammatory diseases, circulatory diseases, skin diseases,
      musculoskeletal diseases and cancers. In cases of ligament injury, obviously the
      temperature of the damaged area increases due to local inflammation; however,
      whether the temperature also increases due to DITI has not been determined. The
      purpose of the present study was to identify whether or not the changes of
      temperature in patient's with medial collateral ligament injury were really due
      to infrared thermography and to determine the applicability of DITI for assessing
      ligament injuries. METHODS: Twenty patient's who underwent DITI for a medial
      collateral ligament injury from September 2012 to June 2014 were included in the
      current study. The thermographic images from the patient's knees were divided to
      cover seven sub-areas: the middle of the patella, and the inferomedial, the
      inferolateral, the superomedial, the superolateral, the medial, and the lateral
      regions of patella. The temperatures of the seven regions were measured, and the
      temperature differences between affected and unaffected regions were analyzed by
      using the Wilcoxon signed rank test. RESULTS: The 20 patient's were composed of
      14 women (70%) and 6 men (30%), with a mean age of 62.15 +/- 15.71 (mean +/-
      standard deviation (SD)) years. The temperature of the affected side, which
      included the middle of the patella, and the inferomedial, the superomedial, the
      superolateral, and the medial regions, showed a significant increase compared to
      that of the unaffected side (P < 0.05). The inferolateral and the lateral regions
      showed no significant changes. CONCLUSION: Our study results suggest that DITI
      can show temperature changes if a patient has a ligament injury and that it can
      be applied in the evaluation of a medial collateral ligament injury.

PMID- 25780720
TI  - Clinical study on constitutional herbal tea for treating chronic fatigue.
AB  - OBJECTIVES: This study was designed to evaluate the efficacy and the safety of
      constitutional herbal tea for treating chronic fatigue with no diagnosed cause,
      which is called Mibyeong in Korea. METHODS: Males and females with ages between
      40 and 59 years who had complained of fatigue for 1 month consistently or for 6
      months intermittently without a definite cause were recruited. At the same time,
      a Chalder fatigue scale (CFS) score of 19 was essential for participation in this
      study. Sixty five subjects completed the entire process, including blood tests
      and tests with medical devices. Five assessments of health status were
      accomplished over 8 weeks by using the CFS and the visual analogue scale (VAS).
      To ensure that the constitutional herbal tea was being safely used, we conducted
      and analyzed renal function and liver function tests. For the diagnosis of the
      Sasang constitution, the Sasang Constitutional Analysis Tool (SCAT) was used, and
      a specialist in Sasang constitutional medicine made the final diagnosis based on
      the SCAT result. Constitutional herbal tea was served four weeks after the first
      visit. The subjects took the constitutional herbal tea twice a day for one month.
      RESULTS: The results are as follows: The CFS and the VAS scores were
      significantly improved for the subjects in the constitutional herbal tea. No
      abnormalities were found on the blood tests to evaluate safety after taking the
      constitutional herbal tea. The improvements in the CFS and the VAS scores due to
      the constitutional herbal tea had no significant differences according to the
      Sasang constitution. CONCLUSION: Constitutional herbal tea may be used to reduce
      fatigue and improve health and has no adverse effect on either the kidney or the
      liver.

PMID- 25780721
TI  - A study on the oral toxicity of mecasin in rats.
AB  - OBJECTIVES: In this study, we investigated the oral toxicity of Gami-Jakyak
      Gamcho buja Decoction (Mecasin) to develop safe treatments. METHODS: All
      experiments were conducted at the Medvill, an institution authorized to perform
      non-clinical studies, under the Good Laboratory Practice (GLP) regulations. In
      order to investigate the oral toxicity of Mecasin, we administered Mecasin orally
      to rats. Sprague-Dawley rats were divided into four groups of five male and five
      female animals per group: group 1 being the control group and groups 2, 3, and 4
      being the experimental groups. Doses of Mecasin, 500 mg/kg, 1,000 mg/kg and 2,000
      mg/kg, were administered to the experimental groups, and a dose of normal saline
      solution, 10 mL/kg, was administered to the control group. We examined the
      survival rate, weight, clinical signs, and gross findings. This study was
      conducted under the approval of the Institutional Animal Ethics Committee.
      RESULTS: No deaths or abnormalities occurred in any of the four groups. Although
      slight decreases in the weights of some female rats were noted on the third day,
      no significant changes in weights or gross findings between the control group and
      the experimental groups were observed. To check for abnormalities in organs, we
      used microscopy to examine representative histological sections of each specified
      organ; the results showed no significant differences in any of the organs.
      CONCLUSION: The results showed that administration of 500 - 2,000 mg/kg of
      Mecasin did not cause any changes in weight or in the results of necropsy
      examinations. It also did not result in any mortalities. The above findings
      suggest that treatment with Mecasin is relatively safe. Further studies on this
      subject are needed to yield more concrete evidence.

PMID- 25780722
TI  - Bee venom pharmacopuncture: an effective treatment for complex regional pain
      syndrome.
AB  - OBJECTIVES: Treating complex regional pain syndrome (CRPS) is difficult because
      it still does not have a recommended therapy. A 29-year-old man was diagnosed
      with CRPS after surgery on his 4(th) and 5(th) left toes 7 years ago. Though he
      had undergone diverse pain treatment, the symptoms persisted, so he visited
      Dunsan Korean Medicine Hospital of Daejeon University. This case report presents
      results on the effect of bee venom pharmacopuncture in treating patient with
      CRPS. METHODS: Bee venom pharmacopuncture (BVP), 0.15 to 0.4 mL dosage, was
      administered at GB43. The treatment was applied each week for a total 14 times.
      The symptoms were evaluated using a numeric rating scale (NRS) and the dosage of
      pain medicine. RESULTS: On the first visit, he was taking an anticonvulsant, a
      trycyclic antidepressant, and an analgesic. On the NRS the worst pain in the toes
      received a score of 8. He also complained of severe pain and hypersensitivity
      when the 4(th) and the 5(th) toes were touched just slightly. Other complaint
      included dyspepsia, rash, and depression. After treatment, on the NRS, the score
      for toe pain was 0, and he no longer needed to take pain medication. During the 4
      months follow-up period, he has remained without pain; neither have additional
      symptoms appeared nor adverse events occurred. CONCLUSION: BVP may have potential
      benefits for treating patients with CRPS.

PMID- 25780723
TI  - Korean herbal medicine for treating henoch-schonlein purpura with yin deficiency:
      five case reports.
AB  - OBJECTIVES: The purpose of this study is to report the clinical effect of Korean
      medicine (KM) treatment for Henoch-Schonlein purpura (HSP). METHODS: Five HSP
      patients who demonstrated a Yin deficiency and who had a history of a previous
      upper respiratory tract infection were included in this study. Four patients had
      arthritis and three had severe stomachache. One of them appeared to have
      proteinuria and hematuria before starting KM treatment. RESULTS: All patients
      were improved with only herbal medicine, Jarotang (JRT). Purpura in the lower
      extremities and abdominal pain, which were not treated by using a corticosteroid,
      disappeared and had not recurred after 6 months. CONCLUSION: These cases indicate
      that JRT may be effective in treating HSP in patients who demonstrate Yin
      deficiency, even though the number of cases was limited to five.

PMID- 25780724
TI  - A high speed multifocal multiphoton fluorescence lifetime imaging microscope for
      live-cell FRET imaging.
AB  - We demonstrate diffraction limited multiphoton imaging in a massively parallel,
      fully addressable time-resolved multi-beam multiphoton microscope capable of
      producing fluorescence lifetime images with sub-50ps temporal resolution. This
      imaging platform offers a significant improvement in acquisition speed over
      single-beam laser scanning FLIM by a factor of 64 without compromising in either
      the temporal or spatial resolutions of the system. We demonstrate FLIM
      acquisition at 500 ms with live cells expressing green fluorescent protein. The
      applicability of the technique to imaging protein-protein interactions in live
      cells is exemplified by observation of time-dependent FRET between the epidermal
      growth factor receptor (EGFR) and the adapter protein Grb2 following stimulation
      with the receptor ligand. Furthermore, ligand-dependent association of HER2-HER3
      receptor tyrosine kinases was observed on a similar timescale and involved the
      internalisation and accumulation or receptor heterodimers within endosomes. These
      data demonstrate the broad applicability of this novel FLIM technique to the
      spatio-temporal dynamics of protein-protein interaction. 

PMID- 25780725
TI  - Developmental and morphological studies in Japanese medaka with ultra-high
      resolution optical coherence tomography.
AB  - We propose ultra-high resolution optical coherence tomography to study the
      morphological development of internal organs in medaka fish in the post-embryonic
      stages at micrometer resolution. Different stages of Japanese medaka were imaged
      after hatching in vivo with an axial resolution of 2.8 um in tissue. Various
      morphological structures and organs identified in the OCT images were then
      compared with the histology. Due to the medaka's close resemblance to
      vertebrates, including humans, these morphological features play an important
      role in morphogenesis and can be used to study diseases that also occur in
      humans. 

PMID- 25780726
TI  - Detailing renal hemodynamics and oxygenation in rats by a combined near-infrared
      spectroscopy and invasive probe approach.
AB  - We hypothesize that combining quantitative near-infrared spectroscopy (NIRS) with
      established invasive techniques will enable advanced insights into renal
      hemodynamics and oxygenation in small animal models. We developed a NIRS
      technique to monitor absolute values of oxygenated and deoxygenated hemoglobin
      and of oxygen saturation of hemoglobin within the renal cortex of rats. This NIRS
      technique was combined with invasive methods to simultaneously record renal
      tissue oxygen tension and perfusion. The results of test procedures including
      occlusions of the aorta or the renal vein, hyperoxia, hypoxia, and hypercapnia
      demonstrated that the combined approach, by providing different but complementary
      information, enables a more comprehensive characterization of renal hemodynamics
      and oxygenation. 

PMID- 25780727
TI  - Application of time-resolved autofluorescence to label-free in vivo optical
      mapping of changes in tissue matrix and metabolism associated with myocardial
      infarction and heart failure.
AB  - We investigate the potential of an instrument combining time-resolved
      spectrofluorometry and diffuse reflectance spectroscopy to measure structural and
      metabolic changes in cardiac tissue in vivo in a 16 week post-myocardial
      infarction heart failure model in rats. In the scar region, we observed changes
      in the fluorescence signal that can be explained by increased collagen content,
      which is in good agreement with histology. In areas remote from the scar tissue,
      we measured changes in the fluorescence signal (p < 0.001) that cannot be
      explained by differences in collagen content and we attribute this to altered
      metabolism within the myocardium. A linear discriminant analysis algorithm was
      applied to the measurements to predict the tissue disease state. When we combine
      all measurements, our results reveal high diagnostic accuracy in the infarcted
      area (100%) and border zone (94.44%) as well as in remote regions from the scar
      (> 77%). Overall, our results demonstrate the potential of our instrument to
      characterize structural and metabolic changes in a failing heart in vivo without
      using exogenous labels. 

PMID- 25780728
TI  - Optical polarization tractography revealed significant fiber disarray in skeletal
      muscles of a mouse model for Duchenne muscular dystrophy.
AB  - Optical polarization tractography (OPT) was recently developed to visualize
      tissue fiber architecture with cellular-level resolution and accuracy. In this
      study, we explored the feasibility of using OPT to study muscle disease in the
      mdx4cv mouse model of Duchenne muscular dystrophy. The freshly dissected tibialis
      anterior muscles of mdx4cv and normal mice were imaged. A "fiber disarray index"
      (FDI) was developed to quantify the myofiber disorganization. In necrotic muscle
      regions of the mdx4cv mice, the FDI was significantly elevated and can be used to
      segment the 3D necrotic regions for assessing the overall muscle damage. These
      results demonstrated the OPT's capability for imaging microscopic fiber
      alternations in muscle research. 

PMID- 25780729
TI  - Optimizing and extending light-sculpting microscopy for fast functional imaging
      in neuroscience.
AB  - A number of questions in system biology such as understanding how dynamics of
      neuronal networks are related to brain function require the ability to capture
      the functional dynamics of large cellular populations at high speed. Recently,
      this has driven the development of a number of parallel and high speed imaging
      techniques such as light-sculpting microscopy, which has been used to capture
      neuronal dynamics at the whole brain and single cell level in small model
      organisms. However, the broader applicability of light-sculpting microcopy is
      limited by the size of volumes for which high speed imaging can be obtained and
      scattering in brain tissue. Here, we present strategies for optimizing the
      present tradeoffs in light-sculpting microscopy. Various scanning modalities in
      light-sculpting microscopy are theoretically and experimentally evaluated, and
      strategies to maximize the obtainable volume speeds, and depth penetration in
      brain tissue using different laser systems are provided. Design-choices,
      important parameters and their trade-offs are experimentally demonstrated by
      performing calcium-imaging in acute mouse-brain slices. We further show that
      synchronization of line-scanning techniques with rolling-shutter read-out of the
      camera can reduce scattering effects and enhance image contrast at depth. 

PMID- 25780730
TI  - Fiber-based polarization-sensitive OCT for birefringence imaging of the anterior
      eye segment.
AB  - We demonstrate a prototype system of polarization-sensitive optical coherence
      tomography (PS-OCT) designed for clinical studies of the anterior eye segment
      imaging. The system can measure Jones matrices of the sample with depth
      multiplexing of two orthogonal incident polarizations and polarization-sensitive
      detection. An optical clock is generated using a quadrature modulator and a
      logical circuit to double the clock frequency. Systematic artifacts in measured
      Jones matrices are theoretically analyzed and numerically compensated using
      signals at the surface of the sample. Local retardation images of filtering blebs
      after trabeculectomy show improved visualization of subconjunctival tissue,
      sclera, and scar tissue of the bleb wall in the anterior eye segment. 

PMID- 25780731
TI  - Non-invasive evaluation of therapeutic response in keloid scar using diffuse
      reflectance spectroscopy.
AB  - The pathogenesis and ideal treatment of keloid are still largely unknown, and it
      is essential to develop an objective assessment of keloid severity to evaluate
      the therapeutic response. We previously reported that our diffuse reflectance
      spectroscopy (DRS) system could assist clinicians in understanding the functional
      and structural condition of keloid scars. The purpose of this study was to
      understand clinical applicability of our DRS system on evaluating the scar
      severity and therapeutic response of keloid. We analyzed 228 spectral data from
      71 subjects with keloid scars. The scars were classified into mild (0-3),
      moderate (4-7) and severe (8-11) according to the Vancouver scar scale. We found
      that as the severity of the scar increased, collagen concentration and water
      content increased, and the reduced scattering coefficient at 800 nm and oxygen
      saturation (SaO2) decreased. Using the DRS system, we found that collagen bundles
      aligned in a specific direction in keloid scars, but not in normal scars. Water
      content and SaO2 may be utilized as reliable parameters for evaluating the
      therapeutic response of keloid. In conclusion, the results obtained here suggest
      that the DRS has potential as an objective technique with which to evaluate
      keloid scar severity. In addition, it may be useful as a tool with which to track
      longitudinal response of scars in response to various therapeutic interventions. 

PMID- 25780732
TI  - Quantitative SHG imaging in osteoarthritis model mice, implying a diagnostic
      application.
AB  - Osteoarthritis (OA) restricts the daily activities of patients and significantly
      decreases their quality of life. The development of non-invasive quantitative
      methods for properly diagnosing and evaluating the process of degeneration of
      articular cartilage due to OA is essential. Second harmonic generation (SHG)
      imaging enables the observation of collagen fibrils in live tissues or organs
      without staining. In the present study, we employed SHG imaging of the articular
      cartilage in OA model mice ex vivo. Consequently, three-dimensional SHG imaging
      with successive image processing and statistical analyses allowed us to
      successfully characterize histopathological changes in the articular cartilage
      consistently confirmed on histological analyses. The quantitative SHG imaging
      technique presented in this study constitutes a diagnostic application of this
      technology in the setting of OA. 

PMID- 25780733
TI  - Error estimation for reconstruction of neuronal spike firing from fast calcium
      imaging.
AB  - Calcium imaging is becoming an increasingly popular technology to indirectly
      measure activity patterns in local neuronal networks. Calcium transients reflect
      neuronal spike patterns allowing for spike train reconstructed from calcium
      traces. The key to judging spiking train authenticity is error estimation.
      However, due to the lack of an appropriate mathematical model to adequately
      describe this spike-calcium relationship, little attention has been paid to
      quantifying error ranges of the reconstructed spike results. By turning attention
      to the data characteristics close to the reconstruction rather than to a complex
      mathematic model, we have provided an error estimation method for the
      reconstructed neuronal spiking from calcium imaging. Real false-negative and
      false-positive rates of 10 experimental Ca(2+) traces were within the estimated
      error ranges and confirmed that this evaluation method was effective. Estimation
      performance of the reconstruction of spikes from calcium transients within a
      neuronal population demonstrated a reasonable evaluation of the reconstructed
      spikes without having real electrical signals. These results suggest that our
      method might be valuable for the quantification of research based on
      reconstructed neuronal activity, such as to affirm communication between
      different neurons. 

PMID- 25780734
TI  - Photoacoustic imaging of acupuncture effect in small animals.
AB  - Acupuncture has been a powerful clinical tool for treating chronic diseases.
      However, there is currently no appropriate method to clarify the therapeutic
      effect of acupuncture. Here, we use photoacoustic tomography (PAT) to study the
      effect of acupuncture on mouse brain blood vessels. Ten healthy mice were
      stimulated with acupuncture needles on two acupoints. PAT images were obtained
      before and after acupuncture. We report that stimulation of certain acupoints
      resulted in changes in hemodynamics/blood flow at these points. The results
      demonstrate that PAT can non-invasively detect blood flow changes in mouse brain
      under acupuncture. This pilot study shows the potential of PAT as a visualization
      tool for illuminating the mechanism of acupuncture and promoting its clinical
      applications. 

PMID- 25780735
TI  - Broadband absorption and reduced scattering spectra of in-vivo skin can be
      noninvasively determined using delta-P1 approximation based spectral analysis.
AB  - Previously, we revealed that a linear gradient line source illumination (LGLSI)
      geometry could work with advanced diffusion models to recover the sample optical
      properties at wavelengths where sample absorption and reduced scattering were
      comparable. In this study, we employed the LGLSI geometry with a broadband light
      source and utilized the spectral analysis to determine the broadband absorption
      and scattering spectra of turbid samples in the wavelength range from 650 to 1350
      nm. The performance of the LGLSI delta-P1 diffusion model based spectral analysis
      was evaluated using liquid phantoms, and it was found that the sample optical
      properties could be properly recovered even at wavelengths above 1000 nm where
      MUs' to MUa ratios were in the range between 1 to 20. Finally, we will
      demonstrate the use of our system for recovering the 650 to 1350 nm absorption
      and scattering spectra of in-vivo human skin. We expect this system can be
      applied to study deep vessel dilation induced hemoglobin concentration variation
      and determine the water and lipid concentrations of in-vivo skin in clinical
      settings in the future. 

PMID- 25780736
TI  - Evaluation of microsurgical tasks with OCT-guided and/or robot-assisted
      ophthalmic forceps.
AB  - Real-time intraocular optical coherence tomography (OCT) visualization of tissues
      with surgical feedback can enhance retinal surgery. An intraocular 23-gauge B
      mode forward-imaging co-planar OCT-forceps, coupling connectors and algorithms
      were developed to form a unique ophthalmic surgical robotic system. Approach to
      the surface of a phantom or goat retina by a manual or robotic-controlled
      forceps, with and without real-time OCT guidance, was performed. Efficiency of
      lifting phantom membranes was examined. Placing the co-planar OCT imaging probe
      internal to the surgical tool reduced instrument shadowing and permitted constant
      tracking. Robotic assistance together with real-time OCT feedback improved depth
      perception accuracy. The first-generation integrated OCT-forceps was capable of
      peeling membrane phantoms despite smooth tips. 

PMID- 25780737
TI  - Spectral modulation interferometry for quantitative phase imaging.
AB  - We propose a spectral-domain interferometric technique, termed spectral
      modulation interferometry (SMI), and present its application to high-sensitivity,
      high-speed, and speckle-free quantitative phase imaging. In SMI, one-dimensional
      complex field of an object is interferometrically modulated onto a broadband
      spectrum. Full-field phase and intensity images are obtained by scanning along
      the orthogonal direction. SMI integrates the high sensitivity of spectral-domain
      interferometry with the high speed of spectral modulation to quantify fast phase
      dynamics, and its dispersive and confocal nature eliminates laser speckles. The
      principle and implementation of SMI are discussed. Its performance is evaluated
      using static and dynamic objects. 

PMID- 25780738
TI  - Fabrication of three-dimensional multi-protein microstructures for cell migration
      and adhesion enhancement.
AB  - In this study, three-dimensional (3D) multi-component microstructures were
      precisely fabricated via multiphoton excited photochemistry using a femtosecond
      laser direct-writing system with proposed repetition positioning and vector
      scanning techniques. Extracellular matrix (ECM) proteins, such as fibronectin
      (FN), are difficult to stack and form 3D structures larger than several-hundred
      microns in height due to the nature of their protein structure. Herein, to
      fabricate complex 3D microstructures with FN, a 3D scaffold was designed and
      formed from bovine serum albumin (BSA), after which human FN was inserted at
      specific locations on the BSA scaffold; in this manner, the fabricated ECM
      microstructure can guide cells in a 3D environment. A human breast cancer cell
      line, MDA-MB-231, was used to investigate the behavior of cell migration and
      adhesion on the fabricated human FN and BSA protein structures. Experimental
      results indicate that many cells are not able to attach or climb on a 3D
      structure's inclined plane without FN support; hence, the influence of cell
      growth in a 3D context with FN should being taken into consideration. This 3D
      multi-protein fabrication technique holds potential for cell studies in designed
      complex 3D ECM scaffolds. 

PMID- 25780739
TI  - High-throughput multiphoton-induced three-dimensional ablation and imaging for
      biotissues.
AB  - In this study, a temporal focusing-based high-throughput multiphoton-induced
      ablation system with axially-resolved widefield multiphoton excitation has been
      successfully applied to rapidly disrupt biotissues. Experimental results
      demonstrate that this technique features high efficiency for achieving large-area
      laser ablation without causing serious photothermal damage in non-ablated
      regions. Furthermore, the rate of tissue processing can reach around 1.6 * 10(6)
      MUm(3)/s in chicken tendon. Moreover, the temporal focusing-based multiphoton
      system can be efficiently utilized in optical imaging through iterating high
      throughput multiphoton-induced ablation machining followed by widefield optical
      sectioning; hence, it has the potential to obtain molecular images for a whole
      bio-specimen. 

PMID- 25780740
TI  - Measurements of the thermal coefficient of optical attenuation at different depth
      regions of in vivo human skins using optical coherence tomography: a pilot study.
AB  - We present detailed measurement results of optical attenuation's thermal
      coefficients (referenced to the temperature of the skin surface) in different
      depth regions of in vivo human forearm skins using optical coherence tomography
      (OCT). We first design a temperature control module with an integrated optical
      probe to precisely control the surface temperature of a section of human skin. We
      propose a method of using the correlation map to identify regions in the skin
      having strong correlations with the surface temperature of the skin and find that
      the attenuation coefficient in these regions closely follows the variation of the
      surface temperature without any hysteresis. We observe a negative thermal
      coefficient of attenuation in the epidermis. While in dermis, the slope signs of
      the thermal coefficient of attenuation are different at different depth regions
      for a particular subject, however, the depth regions with a positive (or
      negative) slope are different in different subjects. We further find that the
      magnitude of the thermal coefficient of attenuation coefficient is greater in
      epidermis than in dermis. We believe the knowledge of such thermal properties of
      skins is important for several noninvasive diagnostic applications, such as OCT
      glucose monitoring, and the method demonstrated in this paper is effective in
      studying the optical and biological properties in different regions of skin. 

PMID- 25780741
TI  - Three-wavelength light control of freely moving Drosophila Melanogaster for less
      perturbation and efficient social-behavioral studies.
AB  - We developed a real-time automated laser-tracking system combined with continuous
      wave 1064-nm infrared or 473-nm blue lasers to provide punishment for studying
      memory in Drosophila Melanogaster. Combining optogenetic tools with laser
      properties, such as 473-nm and 593-nm lasers that activate light sensitive
      proteins in artificial transgenic flies, we can manipulate the specific neuron of
      an assigned fly among multiple flies to investigate neuron circuit relationships
      in social interactions. In restraining condition assay or optogenetic
      experiments, a ventral irradiated system would be more efficient due to higher
      ventral cuticle transmissions and neuron ganglia locations. Therefore, ventral
      irradiated systems cause less perturbation during behavior studies. 

PMID- 25780743
TI  - Noninvasive photoacoustic measurement of the composite indicator dilution curve
      for cardiac output estimation.
AB  - Recently, the measurement of indicator dilution curves using a photoacoustic (PA)
      technology was reported, which showed promising results on the noninvasive
      estimation of cardiac output (CO) that is an important hemodynamic parameter
      useful in various clinical situations. However, in clinical practice, measuring
      PA indicator dilution curves from an arterial blood vessel requires an ultrasound
      transducer array capable of focusing on the targeted artery. This causes several
      challenges on the clinical translation of the PA indicator dilution method, such
      as high sensor cost and complexity. In this paper, we theoretically derived that
      a composite PA indicator dilution curve simultaneously measured from both
      arterial and venous blood vessels can be used to estimate CO correctly. The ex
      vivo and in-vivo experimental results with a flat ultrasound transducer verified
      the developed theory. We believe this new concept would overcome the main
      challenges on the clinical translation of the noninvasive PA indicator dilution
      technology. 

PMID- 25780744
TI  - Digital separation of diaminobenzidine-stained tissues via an automatic color
      filtering for immunohistochemical quantification.
AB  - The digital separation of diaminobenzidine (DAB)-stained tissues from hematoxylin
      background is an important pre-processing step to analyze immunostains. In most
      stain separation methods, specific color channels (for example: RGB, HSI, CMYK)
      or color deconvolution matrices are used to obtain different tissue contrasts
      between DAB- and hematoxylin-stained areas. However, these methods could produce
      incomplete separation or color changes because the color spectra of stains and co
      localized stains overlap in histological images. Therefore, we proposed an
      automatic color-filtering to separate hematoxylin- and DAB-stained tissues. In
      implantation, the RGB images of DAB-labeled immunostains are first converted to 8
      bit BN images by a mathematical translation to produce the largest contrast
      between brown DAB-stained tissues and blue hematoxylin-stained tissues. The first
      valley in the histogram revised by nonuniform quantization is set as the cut-off
      point to obtain a brown filter. DAB-stained tissues are accurately delineated
      from the background counterstain, resulting in DAB-only-image and De-DAB-image.
      Subsequently, a blue filter is designed in the CIE-Lab color space to further
      delineate the hematoxylin-stained tissues from the De-DAB-image. Finally, the
      average values of the remaining pixels of the De-DAB-image are set as the
      background color of the DAB-only-image to manage uneven dyeing and provide DAB
      stained-image for adaptive immunohistochemistry quantitation. Extensive
      experimental results demonstrated that the proposed method has significant
      advantages compared with existing methods in terms of complete stain separation
      without changing the color in DAB-stained areas. 

PMID- 25780742
TI  - In vivo wide-field reflectance/fluorescence imaging and polarization-sensitive
      optical coherence tomography of human oral cavity with a forward-viewing probe.
AB  - We report multimodal imaging of human oral cavity in vivo based on simultaneous
      wide-field reflectance/fluorescence imaging and polarization-sensitive optical
      coherence tomography (PS-OCT) with a forward-viewing imaging probe. Wide-field
      reflectance/fluorescence imaging and PS-OCT were to provide both morphological
      and fluorescence information on the surface, and structural and birefringent
      information below the surface respectively. The forward-viewing probe was
      designed to access the oral cavity through the mouth with dimensions of
      approximately 10 mm in diameter and 180 mm in length. The probe had field of view
      (FOV) of approximately 5.5 mm in diameter, and adjustable depth of field (DOF)
      from 2 mm to 10 mm by controlling numerical aperture (NA) in the detection path.
      This adjustable DOF was to accommodate both requirements for image-based guiding
      with high DOF and high-resolution, high-sensitivity imaging with low DOF. This
      multimodal imaging system was characterized by using a tissue phantom and a mouse
      model in vivo, and was applied to human oral cavity. Information of surface
      morphology and vasculature, and under-surface layered structure and birefringence
      of the oral cavity tissues was obtained. These results showed feasibility of this
      multimodal imaging system as a tool for studying oral cavity lesions in clinical
      applications. 

PMID- 25780745
TI  - Optical metabolic imaging quantifies heterogeneous cell populations.
AB  - The genetic and phenotypic heterogeneity of cancers can contribute to tumor
      aggressiveness, invasion, and resistance to therapy. Fluorescence imaging
      occupies a unique niche to investigate tumor heterogeneity due to its high
      resolution and molecular specificity. Here, heterogeneous populations are
      identified and quantified by combined optical metabolic imaging and subpopulation
      analysis (OMI-SPA). OMI probes the fluorescence intensities and lifetimes of
      metabolic enzymes in cells to provide images of cellular metabolism, and SPA
      models cell populations as mixed Gaussian distributions to identify cell
      subpopulations. In this study, OMI-SPA is characterized by simulation experiments
      and validated with cell experiments. To generate heterogeneous populations, two
      breast cancer cell lines, SKBr3 and MDA-MB-231, were co-cultured at varying
      proportions. OMI-SPA correctly identifies two populations with minimal mean and
      proportion error using the optical redox ratio (fluorescence intensity of NAD(P)H
      divided by the intensity of FAD), mean NAD(P)H fluorescence lifetime, and OMI
      index. Simulation experiments characterized the relationships between sample
      size, data standard deviation, and subpopulation mean separation distance
      required for OMI-SPA to identify subpopulations. 

PMID- 25780746
TI  - Microscopy illumination engineering using a low-cost liquid crystal display.
AB  - Illumination engineering is critical for obtaining high-resolution, high-quality
      images in microscope settings. In a typical microscope, the condenser lens
      provides sample illumination that is uniform and free from glare. The associated
      condenser diaphragm can be manually adjusted to obtain the optimal illumination
      numerical aperture. In this paper, we report a programmable condenser lens for
      active illumination control. In our prototype setup, we used a $15 liquid crystal
      display as a transparent spatial light modulator and placed it at the back focal
      plane of the condenser lens. By setting different binary patterns on the display,
      we can actively control the illumination and the spatial coherence of the
      microscope platform. We demonstrated the use of such a simple scheme for
      multimodal imaging, including bright-field microscopy, darkfield microscopy,
      phase-contrast microscopy, polarization microscopy, 3D tomographic imaging, and
      super-resolution Fourier ptychographic imaging. The reported illumination
      engineering scheme is cost-effective and compatible with most existing platforms.
      It enables a turnkey solution with high flexibility for researchers in various
      communities. From the engineering point-of-view, the reported illumination scheme
      may also provide new insights for the development of multimodal microscopy and
      Fourier ptychographic imaging. 

PMID- 25780747
TI  - In vivo imaging of human photoreceptor mosaic with wavefront sensorless adaptive
      optics optical coherence tomography.
AB  - Wavefront sensorless adaptive optics optical coherence tomography (WSAO-OCT) is a
      novel imaging technique for in vivo high-resolution depth-resolved imaging that
      mitigates some of the challenges encountered with the use of sensor-based
      adaptive optics designs. This technique replaces the Hartmann Shack wavefront
      sensor used to measure aberrations with a depth-resolved image-driven
      optimization algorithm, with the metric based on the OCT volumes acquired in real
      time. The custom-built ultrahigh-speed GPU processing platform and fast modal
      optimization algorithm presented in this paper was essential in enabling real
      time, in vivo imaging of human retinas with wavefront sensorless AO correction.
      WSAO-OCT is especially advantageous for developing a clinical high-resolution
      retinal imaging system as it enables the use of a compact, low-cost and robust
      lens-based adaptive optics design. In this report, we describe our WSAO-OCT
      system for imaging the human photoreceptor mosaic in vivo. We validated our
      system performance by imaging the retina at several eccentricities, and
      demonstrated the improvement in photoreceptor visibility with WSAO compensation. 

PMID- 25780748
TI  - Phthalocyanine photosensitizers as contrast agents for in vivo photoacoustic
      tumor imaging.
AB  - There is a need for contrast agents for non-invasive diagnostic imaging of
      tumors. Herein, Multispectral Optoacoustic Tomography (MSOT) was employed to
      evaluate phthalocyanines commonly used in photodynamic therapy as photoacoustic
      contrast agents. We studied the photoacoustic activity of three water-soluble
      phthalocyanine photosensitizers: phthalocyanine tetrasulfonic acid (PcS4), Zn(II)
      phthalocyanine tetrasulfonic acid (ZnPcS4) and Al(III) phthalocyanine chloride
      tetrasulfonic acid (AlPcS4) in phantom and in tumor-bearing mice to investigate
      the biodistribution and fate of the phthalocyanines in the biological tissues.
      PcS4 was observed to grant good contrast between the different
      reticuloendothelial organs and accumulate in the tumor within an hour of post
      administration. ZnPcS4 and AlPcS4 offered little contrast in photoacoustic
      signals between the organs. PcS4 is a promising photoacoustic contrast agent and
      can be exploited as a photodiagnostic agent. 

PMID- 25780749
TI  - Quantitative polarized light microscopy of human cochlear sections.
AB  - Dysfunction of the inner ear is the most common cause of sensorineural hearing
      loss, which is the most common sensory deficit worldwide. Conventional imaging
      modalities are unable to depict the microanatomy of the human inner ear, hence
      the need to explore novel imaging modalities. We provide the first
      characterization of the polarization dependent optical properties of human
      cochlear sections using quantitative polarized light microscopy (qPLM). Eight
      pediatric cadaveric cochlear sections, aged 0 (term) to 24 months, were selected
      from the US National Temporal Bone Registry, imaged with qPLM and analyzed using
      Image J. Retardance of the bony otic capsule and basilar membrane were
      substantially higher than that of the stria vascularis, spiral ganglion neurons,
      organ of Corti and spiral ligament across the half turns of the spiraling
      cochlea. qPLM provides quantitative information about the human inner ear, and
      awaits future exploration in vivo. 

PMID- 25780750
TI  - A wide field-of-view scanning endoscope for whole anal canal imaging.
AB  - We report a novel wide field-of-view (FOV) scanning endoscope, the AnCam, which
      is based on contact image sensor (CIS) technology used in commercialized business
      card scanners. The AnCam can capture the whole image of the anal canal within 10
      seconds with a resolution of 89 MUm, a maximum FOV of 100 mm * 120 mm, and a
      depth-of-field (DOF) of 0.65 mm at 5.9 line pairs per mm (lp/mm). We demonstrate
      the performance of the AnCam by imaging the entire anal canal of pigs and
      tracking the dynamics of acetowhite testing. We believe the AnCam can potentially
      be a simple and convenient solution for screening of the anal canal for dysplasia
      and for surveillance in patients following treatment for anal cancer. 

PMID- 25780751
TI  - Linear regression models and k-means clustering for statistical analysis of fNIRS
      data.
AB  - We propose a new algorithm, based on a linear regression model, to statistically
      estimate the hemodynamic activations in fNIRS data sets. The main concern guiding
      the algorithm development was the minimization of assumptions and approximations
      made on the data set for the application of statistical tests. Further, we
      propose a K-means method to cluster fNIRS data (i.e. channels) as activated or
      not activated. The methods were validated both on simulated and in vivo fNIRS
      data. A time domain (TD) fNIRS technique was preferred because of its high
      performances in discriminating cortical activation and superficial physiological
      changes. However, the proposed method is also applicable to continuous wave or
      frequency domain fNIRS data sets. 

PMID- 25780752
TI  - Simultaneous photoacoustic and optically mediated ultrasound microscopy: an in
      vivo study.
AB  - We propose the use of thermoelastic (TE) excitation of an ultrasonic (US)
      detector by backscattered laser radiation as a means of upgrading a single
      modality photoacoustic (PA) microscope to dual-modality PA/US imaging at minimal
      cost. The upgraded scanning head of our dual-modality microscope consists of a
      fiber bundle with 14 output arms and a 32MHz polyvinylidene difluoride (PVDF)
      detector with a 34 MHz bandwidth (-6 dB level), 12.7 mm focal length, and a 0.25
      numerical aperture. A single optical pulse delivered through the fiber bundle to
      the biotissue being investigated, in combination with a metalized surface on the
      PVDF detector allows us to obtain both PA and US A-scans. To demonstrate the in
      vivo capabilities of the proposed method we present the results of bimodal
      imaging of the brain of a newborn rat, a mouse tail and a mouse tumor. 

PMID- 25780753
TI  - Dynamic oxygenation measurements using a phosphorescent coating within a mammary
      window chamber mouse model.
AB  - Phosphorescent lifetime imaging was employed to measure the spatial and temporal
      distribution of oxygen partial pressure in tissue under the coverslip of a
      mammary window chamber breast cancer mouse model. A thin platinum-porphyrin
      coating, whose phosphorescent lifetime varies monotonically with oxygen partial
      pressure, was applied to the coverslip surface. Dynamic temporal responses to
      induced modulations in oxygenation levels were measured using this approach. 

PMID- 25780754
TI  - Using network clustering to predict copy number variations associated with health
      disparities.
AB  - Substantial health disparities exist between African Americans and Caucasians in
      the United States. Copy number variations (CNVs) are one form of human genetic
      variations that have been linked with complex diseases and often occur at
      different frequencies among African Americans and Caucasian populations. Here, we
      aimed to investigate whether CNVs with differential frequencies can contribute to
      health disparities from the perspective of gene networks. We inferred network
      clusters from human gene/protein networks based on two different data sources. We
      then evaluated each network cluster for the occurrences of known pathogenic genes
      and genes located in CNVs with different population frequencies, and used false
      discovery rates to rank network clusters. This approach let us identify five
      clusters enriched with known pathogenic genes and with genes located in CNVs with
      different frequencies between African Americans and Caucasians. These clustering
      patterns predict two candidate causal genes located in four population-specific
      CNVs that play potential roles in health disparities. 

PMID- 25780755
TI  - Body composition in Nepalese children using isotope dilution: the production of
      ethnic-specific calibration equations and an exploration of methodological
      issues.
AB  - Background. Body composition is important as a marker of both current and future
      health. Bioelectrical impedance (BIA) is a simple and accurate method for
      estimating body composition, but requires population-specific calibration
      equations. Objectives. (1) To generate population specific calibration equations
      to predict lean mass (LM) from BIA in Nepalese children aged 7-9 years. (2) To
      explore methodological changes that may extend the range and improve accuracy.
      Methods. BIA measurements were obtained from 102 Nepalese children (52 girls)
      using the Tanita BC-418. Isotope dilution with deuterium oxide was used to
      measure total body water and to estimate LM. Prediction equations for estimating
      LM from BIA data were developed using linear regression, and estimates were
      compared with those obtained from the Tanita system. We assessed the effects of
      flexing the arms of children to extend the range of coverage towards lower
      weights. We also estimated potential error if the number of children included in
      the study was reduced. Findings. Prediction equations were generated,
      incorporating height, impedance index, weight and sex as predictors (R (2) 93%).
      The Tanita system tended to under-estimate LM, with a mean error of 2.2%, but
      extending up to 25.8%. Flexing the arms to 90 degrees  increased the lower weight
      range, but produced a small error that was not significant when applied to
      children <16 kg (p 0.42). Reducing the number of children increased the error at
      the tails of the weight distribution. Conclusions. Population-specific isotope
      calibration of BIA for Nepalese children has high accuracy. Arm position is
      important and can be used to extend the range of low weight covered. Smaller
      samples reduce resource requirements, but leads to large errors at the tails of
      the weight distribution. 

PMID- 25780756
TI  - Evolution of resistance and tolerance to herbivores: testing the trade-off
      hypothesis.
AB  - Background. To cope with their natural enemies, plants rely on resistance and
      tolerance as defensive strategies. Evolution of these strategies among natural
      population can be constrained by the absence of genetic variation or because of
      the antagonistic genetic correlation (trade-off) between them. Also, since plant
      defenses are integrated by several traits, it has been suggested that trade-offs
      might occur between specific defense traits. Methodology/Principal Findings. We
      experimentally assessed (1) the presence of genetic variance in tolerance, total
      resistance, and leaf trichome density as specific defense trait, (2) the extent
      of natural selection acting on plant defenses, and (3) the relationship between
      total resistance and leaf trichome density with tolerance to herbivory in the
      annual herb Datura stramonium. Full-sib families of D. stramonium were either
      exposed to natural herbivores (control) or protected from them by a systemic
      insecticide. We detected genetic variance for leaf trichome density, and
      directional selection acting on this character. However, we did not detect a
      negative significant correlation between tolerance and total resistance, or
      between tolerance and leaf trichome density. We argue that low levels of leaf
      damage by herbivores precluded the detection of a negative genetic correlation
      between plant defense strategies. Conclusions/Significance. This study provides
      empirical evidence of the independent evolution of plant defense strategies, and
      a defensive role of leaf trichomes. The pattern of selection should favor
      individuals with high trichomes density. Also, because leaf trichome density
      reduces damage by herbivores and possess genetic variance in the studied
      population, its evolution is not constrained. 

PMID- 25780757
TI  - Availability of mobile phones for discharge follow-up of pediatric Emergency
      Department patients in western Kenya.
AB  - Objective. Mobile phones have been successfully used for Emergency Department
      (ED) patient follow-up in developed countries. Mobile phones are widely available
      in developing countries and may offer a similar potential for follow-up and
      continued care of ED patients in low and middle-income countries. The goal of
      this study was to determine the percentage of families with mobile phones
      presenting to a pediatric ED in western Kenya and rate of response to a follow-up
      phone call after discharge. Methods. A prospective, cross-sectional observational
      study of children presenting to the emergency department of a government referral
      hospital in Eldoret, Kenya was performed. Documentation of mobile phone access,
      including phone number, was recorded. If families had access, consent was
      obtained and families were contacted 7 days after discharge for follow-up.
      Results. Of 788 families, 704 (89.3%) had mobile phone access. Of those families
      discharged from the ED, successful follow-up was made in 83.6% of cases.
      Conclusions. Mobile phones are an available technology for follow-up of patients
      discharged from a pediatric emergency department in resource-limited western
      Kenya. 

PMID- 25780758
TI  - Comparative genomics and phylogenetic discordance of cultivated tomato and close
      wild relatives.
AB  - Background. Studies of ancestry are difficult in the tomato because it crosses
      with many wild relatives and species in the tomato clade that have diverged very
      recently. As a result, the phylogeny in relation to its closest relatives remains
      uncertain. By using the coding sequence from Solanum lycopersicum, S.
      galapagense, S. pimpinellifolium, S. corneliomuelleri, and S. tuberosum and the
      genomic sequence from S. lycopersicum 'Heinz', an heirloom line, S. lycopersicum
      'Yellow Pear', and two of cultivated tomato's closest relatives, S. galapagense
      and S. pimpinellifolium, we have aimed to resolve the phylogenies of these
      closely related species as well as identify phylogenetic discordance in the
      reference cultivated tomato. Results. Divergence date estimates suggest that the
      divergence of S. lycopersicum, S. galapagense, and S. pimpinellifolium happened
      less than 0.5 MYA. Phylogenies based on 8,857 coding sequences support grouping
      of S. lycopersicum and S. galapagense, although two secondary trees are also
      highly represented. A total of 25 genes in our analysis had sites with evidence
      of positive selection along the S. lycopersicum lineage. Whole genome phylogenies
      showed that while incongruence is prevalent in genomic comparisons between these
      genotypes, likely as a result of introgression and incomplete lineage sorting, a
      primary phylogenetic history was strongly supported. Conclusions. Based on
      analysis of these genotypes, S. galapagense appears to be closely related to S.
      lycopersicum, suggesting they had a common ancestor prior to the arrival of an S.
      galapagense ancestor to the Galapagos Islands, but after divergence of the
      sequenced S. pimpinellifolium. Genes showing selection along the S. lycopersicum
      lineage may be important in domestication or selection occurring post
      domestication. Further analysis of intraspecific data in these species will help
      to establish the evolutionary history of cultivated tomato. The use of an
      heirloom line is helpful in deducing true phylogenetic information of S.
      lycopersicum and identifying regions of introgression from wild species. 

PMID- 25780759
TI  - Towards an easier creation of three-dimensional data for embedding into scholarly
      3D PDF (Portable Document Format) files.
AB  - The Portable Document Format (PDF) allows for embedding three-dimensional (3D)
      models and is therefore particularly suitable to communicate respective data,
      especially as regards scholarly articles. The generation of the necessary model
      data, however, is still challenging, especially for inexperienced users. This
      prevents an unrestrained proliferation of 3D PDF usage in scholarly
      communication. This article introduces a new solution for the creation of three
      of types of 3D geometry (point clouds, polylines and triangle meshes), that is
      based on MeVisLab, a framework for biomedical image processing. This solution
      enables even novice users to generate the model data files without requiring
      programming skills and without the need for an intensive training by simply using
      it as a conversion tool. Advanced users can benefit from the full capability of
      MeVisLab to generate and export the model data as part of an overall processing
      chain. Although MeVisLab is primarily designed for handling biomedical image
      data, the new module is not restricted to this domain. It can be used for all
      scientific disciplines. 

PMID- 25780760
TI  - VaRank: a simple and powerful tool for ranking genetic variants.
AB  - Background. Most genetic disorders are caused by single nucleotide variations
      (SNVs) or small insertion/deletions (indels). High throughput sequencing has
      broadened the catalogue of human variation, including common polymorphisms, rare
      variations or disease causing mutations. However, identifying one variation among
      hundreds or thousands of others is still a complex task for biologists,
      geneticists and clinicians. Results. We have developed VaRank, a command-line
      tool for the ranking of genetic variants detected by high-throughput sequencing.
      VaRank scores and prioritizes variants annotated either by Alamut Batch or
      SnpEff. A barcode allows users to quickly view the presence/absence of variants
      (with homozygote/heterozygote status) in analyzed samples. VaRank supports the
      commonly used VCF input format for variants analysis thus allowing it to be
      easily integrated into NGS bioinformatics analysis pipelines. VaRank has been
      successfully applied to disease-gene identification as well as to molecular
      diagnostics setup for several hundred patients. Conclusions. VaRank is
      implemented in Tcl/Tk, a scripting language which is platform-independent but has
      been tested only on Unix environment. The source code is available under the GNU
      GPL, and together with sample data and detailed documentation can be downloaded
      from http://www.lbgi.fr/VaRank/. 

PMID- 25780761
TI  - Development modeling of Lucilia sericata (Diptera: Calliphoridae).
AB  - The relationship between insect development and temperature has been well
      established and has a wide range of uses, including the use of blow flies for
      postmortem (PMI) interval estimations in death investigations. To use insects in
      estimating PMI, we must be able to determine the insect age at the time of
      discovery and backtrack to time of oviposition. Unfortunately, existing
      development models of forensically important insects are only linear
      approximations and do not take into account the curvilinear properties
      experienced at extreme temperatures. A series of experiments were conducted with
      Lucilia sericata, a forensically important blow fly species, that met the
      requirements needed to create statistically valid development models. Experiments
      were conducted over 11 temperatures (7.5 to 32.5  degrees C, at 2.5  degrees C)
      with a 16:8 L:D cycle. Experimental units contained 20 eggs, 10 g beef liver, and
      2.5 cm of pine shavings. Each life stage (egg to adult) had five sampling times.
      Each sampling time was replicated four times, for a total of 20 measurements per
      life stage. For each sampling time, the cups were pulled from the chambers and
      the stage of each maggot was documented morphologically through posterior
      spiracle slits and cephalopharyngeal skeletal development. Data were normally
      distributed with the later larval stages (L3f, L3m) having the most variation
      within and transitioning between stages. The biological minimum was between 7.5 
      degrees C and 10  degrees C, with little egg development and no egg emergence at
      7.5  degrees C. Temperature-induced mortality was highest from 10.0 to 17.5 
      degrees C and 32.5  degrees C. The development data generated illustrates the
      advantages of large datasets in modeling Lucilia sericata development and the
      need for curvilinear models in describing development at environmental
      temperatures near the biological minima and maxima. 

PMID- 25780762
TI  - Population structure of Neisseria gonorrhoeae based on whole genome data and its
      relationship with antibiotic resistance.
AB  - Neisseria gonorrhoeae is the causative agent of gonorrhea, a sexually transmitted
      infection (STI) of major importance. As a result of antibiotic resistance, there
      are now limited options for treating patients. We collected draft genome sequence
      data and associated metadata data on 76 N. gonorrhoeae strains from around the
      globe and searched for known determinants of antibiotics resistance within the
      strains. The population structure and evolutionary forces within the pathogen
      population were analyzed. Our results indicated a cosmopolitan gonoccocal
      population mainly made up of five subgroups. The estimated ratio of recombination
      to mutation (r/m = 2.2) from our data set indicates an appreciable level of
      recombination occurring in the population. Strains with resistance phenotypes to
      more recent antibiotics (azithromycin and cefixime) were mostly found in two of
      the five population subgroups. 

PMID- 25780763
TI  - Arioc: high-throughput read alignment with GPU-accelerated exploration of the
      seed-and-extend search space.
AB  - When computing alignments of DNA sequences to a large genome, a key element in
      achieving high processing throughput is to prioritize locations in the genome
      where high-scoring mappings might be expected. We formulated this task as a
      series of list-processing operations that can be efficiently performed on
      graphics processing unit (GPU) hardware.We followed this approach in implementing
      a read aligner called Arioc that uses GPU-based parallel sort and reduction
      techniques to identify high-priority locations where potential alignments may be
      found. We then carried out a read-by-read comparison of Arioc's reported
      alignments with the alignments found by several leading read aligners. With
      simulated reads, Arioc has comparable or better accuracy than the other read
      aligners we tested. With human sequencing reads, Arioc demonstrates significantly
      greater throughput than the other aligners we evaluated across a wide range of
      sensitivity settings. The Arioc software is available at
      https://github.com/RWilton/Arioc. It is released under a BSD open-source license.

PMID- 25780764
TI  - Prospecting Russula senecis: a delicacy among the tribes of West Bengal.
AB  - Russula senecis, a worldwide distributed mushroom, is exclusively popular among
      the tribal communities of West Bengal for food purposes. The present study
      focuses on its reliable taxonomic identification through macro- and micro
      morphological features, DNA barcoding, confirmation of its systematic placement
      by phylogenetic analyses, myco-chemicals and functional activities. For the first
      time, the complete Internal Transcribed Spacer region of R. senecis has been
      sequenced and its taxonomic position within subsection Foetentinae under series
      Ingratae of the subgen. Ingratula is confirmed through phylogenetic analysis. For
      exploration of its medicinal properties, dried basidiocarps were subjected for
      preparation of a heat stable phenol rich extract (RusePre) using water and
      ethanol as solvent system. The antioxidant activity was evaluated through
      hydroxyl radical scavenging (EC50 5 ug/ml), chelating ability of ferrous ion
      (EC50 0.158 mg/ml), DPPH radical scavenging (EC50 1.34 mg/ml), reducing power
      (EC50 2.495 mg/ml) and total antioxidant activity methods (13.44 ug ascorbic acid
      equivalent/mg of extract). RusePre exhibited antimicrobial potentiality against
      Listeria monocytogenes, Bacillus subtilis, Pseudomonas aeruginosa and
      Staphylococcus aureus. Furthermore, different parameters were tested to
      investigate its chemical composition, which revealed the presence of appreciable
      quantity of phenolic compounds, along with carotenoids and ascorbic acid. HPLC-UV
      fingerprint indicated the probable existence of at least 13 phenolics, of which
      10 were identified (pyrogallol > kaempferol > quercetin > chlorogenic acid >
      ferulic acid, cinnamic acid > vanillic acid > salicylic acid > p-coumaric acid >
      gallic acid). Result from the present work suggests that the fraction, RusePre,
      may open novel prospect as a functional ingredient in antioxidant supplements and
      in drugs to treat infectious disease. 

PMID- 25780765
TI  - Rapid morphological change in black rats (Rattus rattus) after an island
      introduction.
AB  - Rapid morphological change has been shown in rodent populations on islands,
      including endemic deer mice (Peromyscus maniculatus subspp.) on the California
      Channel Islands. Surprisingly, most of these changes were towards a smaller size.
      Black rats were introduced to Anacapa Island in the mid-1800s (probably in 1853)
      and eradicated in 2001-2002. To assess possible changes in these rats since their
      introduction, eleven cranial and four standard external measurements were taken
      from 59 Rattus rattus specimens collected from 1940-2000. All rat cranial traits
      changed 3.06-10.43% (724-2567 d, 0.06-0.42 h), and all became larger. When
      considered in haldanes, these changes are among the fastest on record in any
      organism, and far exceed changes found in other island rodents. These changes
      were confirmed by MANOVA (Wilk's lambda < 0.0005, F d.f.15 = 2974.386, P <
      0.0005), and all 11 cranial traits significantly fit linear regressions. We
      speculate that concurrent changes in mice may have been due in part to
      competition with and/or predation by rats. Future research might evaluate whether
      the vector of mouse evolution on Anacapa is again changing after rat eradication.

PMID- 25780766
TI  - Pallid bands in feathers and associated stable isotope signatures reveal effects
      of severe weather stressors on fledgling sparrows.
AB  - In August 2013, we observed a high incidence (44%) of synchronous bands of
      reduced melanin (a type of fault bar we have termed "pallid bands") across the
      rectrices of juvenile Grasshopper Sparrows (Ammodrammus savannarum) captured near
      El Reno, Oklahoma. Earlier that year, on May 31, the site was struck by a severe
      storm which rained hailstones exceeding 5.5 cm diameter and spawned an historic
      4.2 km-wide tornado <8 km to the south of the site. We hypothesized that this
      stressor had induced the pallid bands. An assessment of Grasshopper Sparrow
      nesting phenology indicated that a large number of nestlings were likely growing
      tail feathers when the storm hit. The pallid bands were restricted to the distal
      half of feathers and their widths significantly increased as a function of
      distance from the tip (i.e., age at formation). We predicted that if stress had
      caused these pallid bands, then a spike in circulating delta (15)N originating
      from tissue catabolism during the stress response would have been incorporated
      into the developing feather. From 18 juveniles captured at the site in August we
      measured delta (15)N and delta (13)C stable isotope ratios within four to five
      0.25-0.40 mg feather sections taken from the distal end of a tail feather; the
      pallid band, if present, was contained within only one section. After accounting
      for individual and across-section variation, we found support for our prediction
      that feather sections containing or located immediately proximal to pallid bands
      (i.e., the pallid band region) would show significantly higher delta (15)N than
      sections outside this region. In contrast, the feathers of juveniles with pallid
      bands compared to normal appearing juveniles showed significantly lower delta
      (15)N. A likely explanation is that the latter individuals hatched after the May
      31 storm and had consumed a trophically-shifted diet relative to juveniles with
      pallid bands. Considering this, the juveniles of normal appearance were
      significantly less abundant within our sample relative to expectations from past
      cohorts (z = - 2.03; p = 0.042) and, in as much, suggested widespread nest losses
      during the storm. Severe weather events may represent major stressors to ground
      nesting birds, especially for recent fledglings. We call for others to exploit
      opportunities to study the effects of severe weather when these rare but
      devastating stressors impact established field research sites. 

PMID- 25780767
TI  - Definition of sampling units begets conclusions in ecology: the case of habitats
      for plant communities.
AB  - In ecology, expert knowledge on habitat characteristics is often used to define
      sampling units such as study sites. Ecologists are especially prone to such
      approaches when prior sampling frames are not accessible. Here we ask to what
      extent can different approaches to the definition of sampling units influence the
      conclusions that are drawn from an ecological study? We do this by comparing a
      formal versus a subjective definition of sampling units within a study design
      which is based on well-articulated objectives and proper methodology. Both
      approaches are applied to tundra plant communities in mesic and snowbed habitats.
      For the formal approach, sampling units were first defined for each habitat in
      concave terrain of suitable slope using GIS. In the field, these units were only
      accepted as the targeted habitats if additional criteria for vegetation cover
      were fulfilled. For the subjective approach, sampling units were defined visually
      in the field, based on typical plant communities of mesic and snowbed habitats.
      For each approach, we collected information about plant community characteristics
      within a total of 11 mesic and seven snowbed units distributed between two
      herding districts of contrasting reindeer density. Results from the two
      approaches differed significantly in several plant community characteristics in
      both mesic and snowbed habitats. Furthermore, differences between the two
      approaches were not consistent because their magnitude and direction differed
      both between the two habitats and the two reindeer herding districts.
      Consequently, we could draw different conclusions on how plant diversity and
      relative abundance of functional groups are differentiated between the two
      habitats depending on the approach used. We therefore challenge ecologists to
      formalize the expert knowledge applied to define sampling units through a set of
      well-articulated rules, rather than applying it subjectively. We see this as
      instrumental for progress in ecology as only rules based on expert knowledge are
      transparent and lead to results reproducible by other ecologists. 

PMID- 25780768
TI  - The use of neuralgia medications to treat sensory neuropathic cough: our
      experience in a retrospective cohort of thirty-two patients.
AB  - Objective. This study sought to: (1) quantify response rate and efficacy of
      amitriptyline, desipramine, and gabapentin in treating sensory neuropathic cough;
      and (2) describe an efficient treatment protocol. Study Design. This study is a
      retrospective case series. Methods. Persons diagnosed with sensory neuropathic
      cough during a one-year period were potential study candidates. To bolster the
      diagnosis credibility, only persons who had been treated elsewhere for
      gastroesophageal reflux disease, asthma, and allergy with no reduction of cough
      were included. Upon diagnosis of sensory neuropathic cough, each person was
      treated with either amitriptyline, desipramine, or gabapentin, titrating the dose
      upward to desired benefit or the dose limit. If the benefit was insufficient,
      another of the medications was used next, using a similar dose escalation
      strategy. Data points included patient demographics, initial and final
      medication, final dose, and degree of improvement. Results. 32 patients met the
      diagnostic and inclusion criteria and had a complete data set. 94% (30 of 32) of
      the patients responded to at least one of the medications. The 32 patients
      undertook a total of 45 single-medication trials. Patients reported symptom
      relief during 78% (14 of 18) of amitriptyline trials, 73% (11 of 15) of
      desipramine trials, and 83% (10 of 12) of gabapentin trials. At final dosage,
      symptom reduction averaged 77% on amitriptyline, 73% on desipramine, and 69% on
      gabapentin. Conclusion. Amitriptyline, desipramine, and gabapentin appear to vary
      in their effectiveness for individual cases of sensory neuropathic cough; across
      a whole cohort, symptom relief was similar in frequency and degree on any of the
      three medications. More evidence is needed to demonstrate more convincingly the
      effectiveness of these medications, but this data set suggests that each of these
      three medications deserves consideration in the codified treatment protocol
      presented here. 

PMID- 25780769
TI  - Improvement of enzymatic saccharification yield in Arabidopsis thaliana by
      ectopic expression of the rice SUB1A-1 transcription factor.
AB  - Saccharification of polysaccharides releases monosaccharides that can be used by
      ethanol-producing microorganisms in biofuel production. To improve plant biomass
      as a raw material for saccharification, factors controlling the accumulation and
      structure of carbohydrates must be identified. Rice SUB1A-1 is a transcription
      factor that represses the turnover of starch and postpones energy-consuming
      growth processes under submergence stress. Arabidopsis was employed to test if
      heterologous expression of SUB1A-1 or SUB1C-1 (a related gene) can be used to
      improve saccharification. Cellulolytic and amylolytic enzymatic treatments
      confirmed that SUB1A-1 transgenics had better saccharification yield than wild
      type (Col-0), mainly from accumulated starch. This improved saccharification
      yield was developmentally controlled; when compared to Col-0, young transgenic
      vegetative plants yielded 200-300% more glucose, adult vegetative plants yielded
      40-90% more glucose and plants in reproductive stage had no difference in yield.
      We measured photosynthetic parameters, starch granule microstructure, and
      transcript abundance of genes involved in starch degradation (SEX4, GWD1),
      juvenile transition (SPL3-5) and meristematic identity (FUL, SOC1) but found no
      differences to Col-0, indicating that starch accumulation may be controlled by
      down-regulation of CONSTANS and FLOWERING LOCUS T by SUB1A-1 as previously
      reported. SUB1A-1 transgenics also offered less resistance to deformation than
      wild-type concomitant to up-regulation of AtEXP2 expansin and BGL2 glucan-1,3,
      beta-glucosidase. We conclude that heterologous SUB1A-1 expression can improve
      saccharification yield and softness, two traits needed in bioethanol production. 

PMID- 25780770
TI  - Small sample sizes in the study of ontogenetic allometry; implications for
      palaeobiology.
AB  - Quantitative morphometric analyses, particularly ontogenetic allometry, are
      common methods used in quantifying shape, and changes therein, in both extinct
      and extant organisms. Due to incompleteness and the potential for restricted
      sample sizes in the fossil record, palaeobiological analyses of allometry may
      encounter higher rates of error. Differences in sample size between fossil and
      extant studies and any resulting effects on allometric analyses have not been
      thoroughly investigated, and a logical lower threshold to sample size is not
      clear. Here we show that studies based on fossil datasets have smaller sample
      sizes than those based on extant taxa. A similar pattern between vertebrates and
      invertebrates indicates this is not a problem unique to either group, but common
      to both. We investigate the relationship between sample size, ontogenetic
      allometric relationship and statistical power using an empirical dataset of skull
      measurements of modern Alligator mississippiensis. Across a variety of
      subsampling techniques, used to simulate different taphonomic and/or sampling
      effects, smaller sample sizes gave less reliable and more variable results, often
      with the result that allometric relationships will go undetected due to Type II
      error (failure to reject the null hypothesis). This may result in a false
      impression of fewer instances of positive/negative allometric growth in fossils
      compared to living organisms. These limitations are not restricted to fossil data
      and are equally applicable to allometric analyses of rare extant taxa. No
      mathematically derived minimum sample size for ontogenetic allometric studies is
      found; rather results of isometry (but not necessarily allometry) should not be
      viewed with confidence at small sample sizes. 

PMID- 25780771
TI  - Found in transition: applying milestones to three unique discharge curricula.
AB  - Introduction. A safe and effective transition from hospital to post-acute care is
      a complex and important physician competency. Milestones and Entrustable
      Professional Activities (EPA) form the new educational rubric in Graduate Medical
      Education Training. "A safe and effective discharge from the hospital" is an EPA
      ripe for educational innovation. Methods. The authors collaborated in a
      qualitative process called mapping to define 22 of 142 Internal Medicine (IM)
      curricular milestones related to the transition of care. Fifty-five participant
      units at an Association for Program Directors in Internal Medicine (APDIM)
      workshop prioritized the milestones, using a validated ranking process called Q
      sort. We analyzed the Q-sort results, which rank the milestones in order of
      priority. We then applied this ranking to three innovative models of training IM
      residents in the transitions of care: Simulation (S), Discharge Clinic Feedback
      (DCF) and TRACER (T). Results. We collected 55 Q-sort rankings from particpants
      at the APDIM workshop. We then identified which milestones are a focus of the
      three innovative models of training in the transition of care: Simulation = 5 of
      22 milestones, Discharge Clinic Feedback = 9 of 22 milestones, and TRACER = 7 of
      22 milestones. Milestones identified in each innovation related to one of the top
      8 prioritized milestones 75% of the time; thus, more frequently than the
      milestones with lower priority. Two milestones are shared by all three curricula:
      Utilize patient-centered education and Ensure succinct written communication. Two
      other milestones are shared by two curricula: Manage and coordinate care
      transitions across multiple delivery systems and Customize care in the context of
      the patient's preferences. If you combine the three innovations, all of the top 8
      milestones are included. Discussion. The milestones give us a context to share
      individual innovations and to compare and contrast using a standardized frame. We
      demonstrate that the three unique discharge curricula in aggregate capture all of
      the highest prioritized milestones for this discharge EPA. 

PMID- 25780772
TI  - Cell kinetics during regeneration in the sponge Halisarca caerulea: how local is
      the response to tissue damage?
AB  - Sponges have a remarkable capacity to rapidly regenerate in response to wound
      infliction. In addition, sponges rapidly renew their filter systems (choanocytes)
      to maintain a healthy population of cells. This study describes the cell kinetics
      of choanocytes in the encrusting reef sponge Halisarca caerulea during early
      regeneration (0-8 h) following experimental wound infliction. Subsequently, we
      investigated the spatial relationship between regeneration and cell proliferation
      over a six-day period directly adjacent to the wound, 1 cm, and 3 cm from the
      wound. Cell proliferation was determined by the incorporation of 5-bromo-2'
      deoxyuridine (BrdU). We demonstrate that during early regeneration, the growth
      fraction of the choanocytes (i.e., the percentage of proliferative cells)
      adjacent to the wound is reduced (7.0 +/- 2.5%) compared to steady-state,
      undamaged tissue (46.6 +/- 2.6%), while the length of the cell cycle remained
      short (5.6 +/- 3.4 h). The percentage of proliferative choanocytes increased over
      time in all areas and after six days of regeneration choanocyte proliferation
      rates were comparable to steady-state tissue. Tissue areas farther from the wound
      had higher rates of choanocyte proliferation than areas closer to the wound,
      indicating that more resources are demanded from tissue in the immediate vicinity
      of the wound. There was no difference in the number of proliferative mesohyl
      cells in regenerative sponges compared to steady-state sponges. Our data suggest
      that the production of collagen-rich wound tissue is a key process in tissue
      regeneration for H. caerulea, and helps to rapidly occupy the bare substratum
      exposed by the wound. Regeneration and choanocyte renewal are competing and
      negatively correlated life-history traits, both essential to the survival of
      sponges. The efficient allocation of limited resources to these life-history
      traits has enabled the ecological success and diversification of sponges. 

PMID- 25780773
TI  - Prolonged decay of molecular rate estimates for metazoan mitochondrial DNA.
AB  - Evolutionary timescales can be estimated from genetic data using the molecular
      clock, often calibrated by fossil or geological evidence. However, estimates of
      molecular rates in mitochondrial DNA appear to scale negatively with the age of
      the clock calibration. Although such a pattern has been observed in a limited
      range of data sets, it has not been studied on a large scale in metazoans. In
      addition, there is uncertainty over the temporal extent of the time-dependent
      pattern in rate estimates. Here we present a meta-analysis of 239 rate estimates
      from metazoans, representing a range of timescales and taxonomic groups. We found
      evidence of time-dependent rates in both coding and non-coding mitochondrial
      markers, in every group of animals that we studied. The negative relationship
      between the estimated rate and time persisted across a much wider range of
      calibration times than previously suggested. This indicates that, over long time
      frames, purifying selection gives way to mutational saturation as the main driver
      of time-dependent biases in rate estimates. The results of our study stress the
      importance of accounting for time-dependent biases in estimating mitochondrial
      rates regardless of the timescale over which they are inferred. 

PMID- 25780774
TI  - Artemisinin mimics calorie restriction to trigger mitochondrial biogenesis and
      compromise telomere shortening in mice.
AB  - Calorie restriction is known to extend lifespan among organisms by a debating
      mechanism underlying nitric oxide-driven mitochondrial biogenesis. We report here
      that nitric oxide generators including artemisinin, sodium nitroprusside, and L
      arginine mimics calorie restriction and resembles hydrogen peroxide to initiate
      the nitric oxide signaling cascades and elicit the global antioxidative responses
      in mice. The large quantities of antioxidant enzymes are correlated with the low
      levels of reactive oxygen species, which allow the down-regulation of tumor
      suppressors and accessory DNA repair partners, eventually leading to the
      compromise of telomere shortening. Accompanying with the up-regulation of signal
      transducers and respiratory chain signatures, mitochondrial biogenesis occurs
      with the elevation of adenosine triphosphate levels upon exposure of mouse
      skeletal muscles to the mimetics of calorie restriction. In conclusion, calorie
      restriction-triggered nitric oxide provides antioxidative protection and
      alleviates telomere attrition via mitochondrial biogenesis, thereby maintaining
      chromosomal stability and integrity, which are the hallmarks of longevity. 

PMID- 25780775
TI  - Wing bone laminarity is not an adaptation for torsional resistance in bats.
AB  - Torsional loading is a common feature of skeletal biomechanics during vertebrate
      flight. The importance of resisting torsional loads is best illustrated by the
      convergence of wing bone structure (e.g., long with thin walls) across extant
      bats and birds. Whether or not such a convergence occurs at the microstructural
      level is less clear. In volant birds, the humeri and ulnae often contain abundant
      laminar bony tissue in which primary circumferential vascular canals course
      concentrically about the long axis of the bone. These circumferential canals and
      the matrix surrounding them presumably function to resist the tissue-level shear
      stress caused by flight-induced torsion. Here, we assess whether or not laminar
      bone is a general adaptive feature in extant flying vertebrates using a
      histological analysis of bat bones. We sampled the humeri from six adult taxa
      representing a broad phylogenetic and body size range (6-1,000 g). Transverse
      thick sections were prepared from the midshaft of each humerus. Bone tissue was
      classified based on the predominant orientation of primary vascular canals. Our
      results show that humeri from bats across a wide phylogenetic and body size range
      do not contain any laminar bone. Instead, humeri are essentially avascular in
      bats below about 100 g and are poorly vascularized with occasional longitudinal
      to slightly radial canals in large bats. In contrast, humeri from birds across a
      comparable size range (40-1,000 g) are highly vascularized with a wide range in
      bone laminarity. Phylogenetically-informed scaling analyses reveal that the
      difference in vascularity between birds and bats is best explained by higher
      somatic relative growth rates in birds. The presence of wing bone laminarity in
      birds and its absence in bats suggests that laminar bone is not a necessary
      biomechanical feature in flying vertebrates and may be apomorphic to birds. 

PMID- 25780776
TI  - CauseMap: fast inference of causality from complex time series.
AB  - Background. Establishing health-related causal relationships is a central pursuit
      in biomedical research. Yet, the interdependent non-linearity of biological
      systems renders causal dynamics laborious and at times impractical to
      disentangle. This pursuit is further impeded by the dearth of time series that
      are sufficiently long to observe and understand recurrent patterns of flux.
      However, as data generation costs plummet and technologies like wearable devices
      democratize data collection, we anticipate a coming surge in the availability of
      biomedically-relevant time series data. Given the life-saving potential of these
      burgeoning resources, it is critical to invest in the development of open source
      software tools that are capable of drawing meaningful insight from vast amounts
      of time series data. Results. Here we present CauseMap, the first open source
      implementation of convergent cross mapping (CCM), a method for establishing
      causality from long time series data (?25 observations). Compared to existing
      time series methods, CCM has the advantage of being model-free and robust to
      unmeasured confounding that could otherwise induce spurious associations. CCM
      builds on Takens' Theorem, a well-established result from dynamical systems
      theory that requires only mild assumptions. This theorem allows us to reconstruct
      high dimensional system dynamics using a time series of only a single variable.
      These reconstructions can be thought of as shadows of the true causal system. If
      reconstructed shadows can predict points from opposing time series, we can infer
      that the corresponding variables are providing views of the same causal system,
      and so are causally related. Unlike traditional metrics, this test can establish
      the directionality of causation, even in the presence of feedback loops.
      Furthermore, since CCM can extract causal relationships from times series of,
      e.g., a single individual, it may be a valuable tool to personalized medicine. We
      implement CCM in Julia, a high-performance programming language designed for
      facile technical computing. Our software package, CauseMap, is platform
      independent and freely available as an official Julia package. Conclusions.
      CauseMap is an efficient implementation of a state-of-the-art algorithm for
      detecting causality from time series data. We believe this tool will be a
      valuable resource for biomedical research and personalized medicine. 

PMID- 25780777
TI  - Differential contribution of soil biota groups to plant litter decomposition as
      mediated by soil use.
AB  - Plant decomposition is dependant on the activity of the soil biota and its
      interactions with climate, soil properties, and plant residue inputs. This work
      assessed the roles of different groups of the soil biota on litter decomposition,
      and the way they are modulated by soil use. Litterbags of different mesh sizes
      for the selective exclusion of soil fauna by size (macro, meso, and microfauna)
      were filled with standardized dried leaves and placed on the same soil under
      different use intensities: naturalized grasslands, recent agriculture, and
      intensive agriculture fields. During five months, litterbags of each mesh size
      were collected once a month per system with five replicates. The remaining mass
      was measured and decomposition rates calculated. Differences were found for the
      different biota groups, and they were dependant on soil use. Within systems, the
      results show that in the naturalized grasslands, the macrofauna had the highest
      contribution to decomposition. In the recent agricultural system it was the
      combined activity of the macro- and mesofauna, and in the intensive agricultural
      use it was the mesofauna activity. These results underscore the relative
      importance and activity of the different groups of the edaphic biota and the
      effects of different soil uses on soil biota activity. 

PMID- 25780778
TI  - Subject-specific body segment parameter estimation using 3D photogrammetry with
      multiple cameras.
AB  - Inertial properties of body segments, such as mass, centre of mass or moments of
      inertia, are important parameters when studying movements of the human body.
      However, these quantities are not directly measurable. Current approaches include
      using regression models which have limited accuracy: geometric models with
      lengthy measuring procedures or acquiring and post-processing MRI scans of
      participants. We propose a geometric methodology based on 3D photogrammetry using
      multiple cameras to provide subject-specific body segment parameters while
      minimizing the interaction time with the participants. A low-cost body scanner
      was built using multiple cameras and 3D point cloud data generated using
      structure from motion photogrammetric reconstruction algorithms. The point cloud
      was manually separated into body segments, and convex hulling applied to each
      segment to produce the required geometric outlines. The accuracy of the method
      can be adjusted by choosing the number of subdivisions of the body segments. The
      body segment parameters of six participants (four male and two female) are
      presented using the proposed method. The multi-camera photogrammetric approach is
      expected to be particularly suited for studies including populations for which
      regression models are not available in literature and where other geometric
      techniques or MRI scanning are not applicable due to time or ethical constraints.

PMID- 25780779
TI  - Immigration rates and species niche characteristics affect the relationship
      between species richness and habitat heterogeneity in modeled meta-communities.
AB  - The positive relationship between habitat heterogeneity and species richness is a
      cornerstone of ecology. Recently, it was suggested that this relationship should
      be unimodal rather than linear due to a tradeoff between environmental
      heterogeneity and population sizes. Increased environmental heterogeneity will
      decrease effective habitat sizes, which in turn will increase the rate of local
      species extinctions. The occurrence of the unimodal richness-heterogeneity
      relationship at the habitat scale was confirmed in both empirical and theoretical
      studies. However, it is unclear whether it can occur at broader spatial scales,
      for meta-communities in diverse and patchy landscapes. Here, I used a spatially
      explicit meta-community model to quantify the roles of two species-level
      characteristics, niche width and immigration rates, on the type of the richness
      heterogeneity relationship at the landscape scale. I found that both positive and
      unimodal richness-heterogeneity relationships can occur in meta-communities in
      patchy landscapes. The type of the relationship was affected by the interactions
      between inter-patch immigration rates and species' niche widths. Unimodal
      relationships were prominent in meta-communities comprising species with wide
      niches but low inter-patch immigration rates. In contrast, meta-communities
      consisting of species with narrow niches and high immigration rates exhibited
      positive relationships. Meta-communities comprising generalist species are
      therefore likely to exhibit unimodal richness-heterogeneity relationships as long
      as low immigration rates prevent rescue effects and patches are small. The
      richness-heterogeneity relationship at the landscape scale is dictated by
      species' niche widths and inter-patch immigration rates. These immigration rates,
      in turn, depend on the interaction between species dispersal capabilities and
      habitat connectivity, highlighting the roles of both species traits and landscape
      structure in generating the richness-heterogeneity relationship at the landscape
      scale. 

PMID- 25780780
TI  - Efficacy and safety of low molecular weight heparin compared to unfractionated
      heparin for chronic outpatient hemodialysis in end stage renal disease:
      systematic review and meta-analysis.
AB  - Background. Low molecular weight heparin (LMWH) is an effective anti-coagulant
      for thrombotic events. However, due to its predominant renal clearance, there are
      concerns that it might be associated with increased bleeding in patients with
      renal disease. Objectives. We systematically evaluated the efficacy and safety of
      LMWH compared to unfractionated heparin (UH) in end stage renal disease (ESRD)
      patients. Search Methods. Pubmed, Embase and cochrane central were searched for
      eligible citations. Selection Criteria. Randomized controlled trials, comparing
      LMWH and UH, involving adult (age > 18 years), ESRD patients receiving
      outpatient, chronic, intermittent hemodialysis were included. Data Collection and
      Analysis. Two independent reviewers performed independent data abstraction. I2
      statistic was used to assess heterogeneity. Random effects model was used for
      meta-analysis. Results. Nineteen studies were included for systematic review and
      4 were included for meta-analysis. There were no significant differences between
      LMWH and UFH for extracorporeal circuit thrombosis [risk ratio: 1 (95% CI [0.62
      1.62])] and bleeding complications [risk ratio: 1.16 (95% CI [0.62-2.15])].
      Conclusions. LMWH is as safe and effective as UFH. Considering the poor quality
      of studies included for the review, larger well conducted RCTs are required
      before conclusions can be drawn. 

PMID- 25780781
TI  - Blood transfusion practice in a referral cardiovascular center in tehran, iran: a
      critical point of view.
AB  - BACKGROUND: Unnecessary perioperative transfusions are likely to be related to
      increased morbidity and additional costs in cardiac surgery. OBJECTIVES: The aim
      of this study was to evaluate the blood transfusion practice during and after
      adult cardiac surgery in a referral university hospital in Iran. PATIENTS AND
      METHODS: In a descriptive study, we collected data from 153 adult patients
      underwent cardiac surgery at Rajaie Cardiovascular Medical and Research Center,
      Tehran, Iran from January to March 2013. The variables were patients'
      demographic, operative and post-operative data and the numbers of transfused
      packed red blood cell (PC) units and fresh frozen plasma (FFP) during and after
      cardiac surgery. Then we evaluated patients' and physicians' related causes of
      relatively increased transfusion rate in our patients and compared them with
      literature. RESULTS: Of 153 patients, 96.8% received PC and 54.9% transfused FFP
      during or after surgery. Most of the transfusions were done after operation in
      intensive care unit (ICU). Also, 20% and 17% of the patients underwent
      transfusion of more than 6 units of PC and FFP, respectively. The mean left
      ventricular ejection fraction of the patients was 42.5 +/- 10.9%. A significant
      number of patients had anemia (especially women) or received anticoagulants or
      antiplatelet agents preoperatively. Thirteen percent of the patients underwent
      emergency operations and 12.3% had re-exploration. CONCLUSIONS: The results of
      this study demonstrate that the cardiac surgery patients receive a relatively
      greater number of PC or FFP units during and after the operation in our center.
      This finding may be explained to some extent by the fact that the sicker and more
      co-morbid patients referred to our center and such patients are more anemic and
      undergoing more emergent and complex procedures. Moreover, Transfusion strategy
      or protocol should be updated, especially after the operation in ICU.

PMID- 25780782
TI  - Autonomic dysfunction predicts poor physical improvement after cardiac
      rehabilitation in patients with heart failure.
AB  - BACKGROUND: Cardiac autonomic dysfunction, clinically expressed by reduced heart
      rate variability (HRV), is present in patients with congestive heart failure
      (CHF) and is related to the degree of left ventricular dysfunction. In athletes,
      HRV is an indicator of ability to improve performance. No similar data are
      available for CHF. OBJECTIVES: The aim of this study was to assess whether HRV
      could predict the capability of CHF patients to improve physical fitness after a
      short period of exercise-based cardiac rehabilitation (CR). PATIENTS AND METHODS:
      This was an observational, non-randomized study, conducted on 57 patients with
      advanced CHF, admitted to a residential cardiac rehabilitation unit 32 +/- 22
      days after an episode of acute heart failure. Inclusion criteria were sinus
      rhythm, stable clinical conditions, no diabetes and ejection fraction <= 35%. HRV
      (time-domain) and mean and minimum heart rate (HR) were evaluated using 24-h
      Holter at admission. Patients' physical fitness was evaluated at admission by 6
      minute walking test (6MWT) and reassessed after two weeks of intensive exercise
      based CR. Exercise capacity was evaluated by a symptom-limited cardiopulmonary
      exercise test (CPET). RESULTS: Patients with very depressed HRV (SDNN 55.8 +/-
      10.0 ms) had no improvement in their walking capacity after short CR, walked
      shorter absolute distances at final 6MWT (348 +/- 118 vs. 470 +/- 109 m; P =
      0.027) and developed a peak-VO2 at CPET significantly lower than patients with
      greater HRV parameters (11.4 +/- 3.7 vs. an average > 16 +/- 4 mL/kg/min).
      Minimum HR, but not mean HR, showed a negative correlation (rho = -0.319) with
      CPET performance. CONCLUSIONS: In patients with advanced CHF, depressed HRV and
      higher minimum HR were predictors of poor working capacity after a short period
      of exercise-based CR. An individualized and intensive rehabilitative intervention
      should be considered for these patients.

PMID- 25780783
TI  - Acute myocarditis or the kounis syndrome: role of cardiac MRI and speckle
      tracking echocardiography in diagnosis.
AB  - INTRODUCTION: The Kounis syndrome and acute myocarditis are two distinct clinical
      entities, which could share nearly the same symptomatology as well as ECG
      (electrocardiography) and laboratory findings. CASE PRESENTATION: First case was
      a 39-year-old male presented with acute chest pain and inferolateral ST elevation
      on ECG. The second case was a 29-year-old male presented with chest pain and
      diffuses ST elevation. Diagnosis of acute myocarditis was achieved by
      demonstrating subepicardial contrast enhancement as well as atypical involvement
      in both of our clinical cases. CONCLUSIONS: We reported two cases in which
      specific imaging modalities (cardiac magnetic resonance imaging and speckle
      tracking echocardiography) were used when the signs and symptoms were
      indistinguishable.

PMID- 25780784
TI  - RENASICA II: A Mexican acute myocardial infarction registry that highlights the
      importance of regional registries.
AB  - Cardiovascular diseases are the leading cause of death, worldwide, with
      disproportionate representation in low- and middle-income countries (LMICs). The
      Registro Nacional de los Sindromes Coronarios Agudos II (RENASICA II)
      investigators reported smoking, hypertension and diabetes were the main risk
      factors among Mexican patients presenting with ST-elevation myocardial infarction
      (STEMI). Fibrinolytic therapy was administered to 37%. Primary percutaneous
      coronary intervention (PPCI) was performed in only 15% of patients. 30-day
      mortality was 10%. This study highlights the importance of conducting regional
      registries for quality improvement. 

PMID- 25780786
TI  - Endothelial dysfunction and cardiovascular disease.

PMID- 25780788
TI  - Niemann-Pick C1-Like 1 protein: Another target for treatment of dyslipidemia?
      Evidence from the Myocardial Infarction Genetic Consortium and IMPROVE-IT trials.

PMID- 25780787
TI  - Tissue plasminogen activator-based clot busting: Controlled delivery approaches.
AB  - Cardiovascular diseases are the leading cause of death worldwide. Thrombosis, the
      formation of blood clot (thrombus) in the circulatory system obstructing the
      blood flow, is one of the main causes behind various ischemic arterial syndromes
      such as ischemic stroke and myocardial infarction, as well as vein syndromes such
      as deep vein thrombosis, and consequently, pulmonary emboli. Several thrombolytic
      agents have been developed for treating thrombosis, the most common being tissue
      plasminogen activator (tPA), administrated systemically or locally via IV
      infusion directly proximal to the thrombus, with the aim of restoring and
      improving the blood flow. TPA triggers the dissolution of thrombi by inducing the
      conversion of plasminogen to protease plasmin followed by fibrin digestion that
      eventually leads to clot lysis. Although tPA provides powerful thrombolytic
      activity, it has many shortcomings, including poor pharmacokinetic profiles,
      impairment of the reestablishment of normal coronary flow, and impairment of
      hemostasis, leading to life-threatening bleeding consequences. The bleeding
      consequence is ascribed to the ability of tPA to circulate throughout the body
      and therefore can lysis all blood clots in the circulation system, even the good
      ones that prevent the bleeding and promote injury repair. This review provides an
      overview of the different delivery approaches for tPA including: liposomes,
      ultrasound-triggered thrombolysis, anti-fibrin antibody-targeted tPA, camouflaged
      tPA, tpA-loaded microcarriers, and nano-modulated delivery approaches. 

PMID- 25780789
TI  - GAUSS-2, RUTHERFORD-2, LAPLACE-2, DESCARTES, and TESLA Part B: PCSK9 inhibitors
      gain momentum.

PMID- 25780785
TI  - The role of phosphodiesterase inhibitors in the management of pulmonary vascular
      diseases.
AB  - Phosphodiesterase inhibitors (PDE) can be used as therapeutic agents for various
      diseases such as dementia, depression, schizophrenia and erectile dysfunction in
      men, as well as congestive heart failure, chronic obstructive pulmonary disease,
      rheumatoid arthritis, other inflammatory diseases, diabetes and various other
      conditions. In this review we will concentrate on one type of PDE, mainly PDE5
      and its role in pulmonary vascular diseases. 

PMID- 25780790
TI  - Diabetes and silent atrial fibrillation: A dangerous liaison?
AB  - Diabetic patients have higher risk of stroke when compared to non-diabetics and
      in 25% of patients the cause of stroke is unknown. Marfella et al hypothesized
      that subclinical episodes of atrial fibrillation may be a common etiologic
      factor. 464 type-2 diabetic patients were compared to 240 health controls and
      were followed-up for 37 months. Silent cerebral infarcts at baseline were more
      common among diabetic patients with silent AF (176 patients) when compared to non
      silent AF group (288 patients) (61% vs. 29%; p < 0.001) and was associated with
      higher number of stroke at follow-up. 

PMID- 25780791
TI  - COMPARE and Pediatric Heart Network Investigator trials: Losartan finally
      validated in humans with Marfan, but much work remains!
AB  - A landmark study by Habashi et al(1) in 2006 documented for the first time both
      the prevention and reversal of structural changes in the aorta associated with
      Marfan syndrome, via pharmacological means. This study, carried out in a rat
      model, concluded that such results were due to an inhibitor effect by the drug
      losartan on TGB-beta1 (Figure 1). Habashi's paper prompted some physicians, in
      the absence of human trials, to begin the clinical off-label use of losartan on
      Marfan patients, arguing that this was justified due to the drug's excellent
      safety profile. This has caused some controversy. Two significant randomized
      human trials of losartan in Marfan patients have since been conducted, which
      contribute different but valuable elements to the debate; the COMPARE trial
      demonstrated a significantly lower increase in aortic root diameter among study
      subjects receiving losartan compared with a placebo group after 3 years, although
      no significant differences were observed in aortic diameter beyond the root
      itself. A more recently concluded trial by Lacro et al(2) from the Paediatric
      Heart Network, comparing losartan with atenolol (and no placebo group), appeared
      to show no comparative benefit with respect to the rate of aortic dilatation over
      three years among the losartan users compared with study patients given atenolol,
      with both groups of patients experiencing a similar decrease in the rate of
      dilatation over the 3 year follow-up. Both studies suggest a positive impact of
      losartan on aortic dilation in humans with Marfan, but they also highlight a
      number of important questions that remain unanswered. Further trials are clearly
      needed in order to assess optimal dosing and to guide timing of therapy, and also
      to further assess the potential and comparative effectiveness of both losartan
      and beta-blockers, individually and in combination, as therapeutic treatments for
      aortic protection of different groups of patients with Marfan syndrome. 

PMID- 25780792
TI  - Lessons from the PURE study.

PMID- 25780793
TI  - Role of prostacyclin in pulmonary hypertension.
AB  - Prostacyclin is a powerful cardioprotective hormone released by the endothelium
      of all blood vessels. Prostacyclin exists in equilibrium with other vasoactive
      hormones and a disturbance in the balance of these factors leads to
      cardiovascular disease including pulmonary arterial hypertension. Since it's
      discovery in the 1970s concerted efforts have been made to make the best
      therapeutic utility of prostacyclin, particularly in the treatment of pulmonary
      arterial hypertension. This has centred on working out the detailed pharmacology
      of prostacyclin and then synthesising new molecules based on its structure that
      are more stable or more easily tolerated. In addition, newer molecules have been
      developed that are not analogues of prostacyclin but that target the receptors
      that prostacyclin activates. Prostacyclin and related drugs have without doubt
      revolutionised the treatment and management of pulmonary arterial hypertension
      but are seriously limited by side effects within the systemic circulation. With
      the dawn of nanomedicine and targeted drug or stem cell delivery systems it will,
      in the very near future, be possible to make new formulations of prostacyclin
      that can evade the systemic circulation allowing for safe delivery to the
      pulmonary vessels. In this way, the full therapeutic potential of prostacyclin
      can be realised opening the possibility that pulmonary arterial hypertension will
      become, if not curable, a chronic manageable disease that is no longer fatal.
      This review discusses these and other issues relating to prostacyclin and its use
      in pulmonary arterial hypertension. 

PMID- 25780794
TI  - Arab gene geography: From population diversities to personalized medical
      genomics.
AB  - Genetic disorders are not equally distributed over the geography of the Arab
      region. While a number of disorders have a wide geographical presence
      encompassing 10 or more Arab countries, almost half of these disorders occur in a
      single Arab country or population. Nearly, one-third of the genetic disorders in
      Arabs result from congenital malformations and chromosomal abnormalities, which
      are also responsible for a significant proportion of neonatal and perinatal
      deaths in Arab populations. Strikingly, about two-thirds of these diseases in
      Arab patients follow an autosomal recessive mode of inheritance. High fertility
      rates together with increased consanguineous marriages, generally noticed in Arab
      populations, tend to increase the rates of genetic and congenital abnormalities.
      Many of the nearly 500 genes studied in Arab people revealed striking spectra of
      heterogeneity with many novel and rare mutations causing large arrays of clinical
      outcomes. In this review we provided an overview of Arab gene geography, and
      various genetic abnormalities in Arab populations, including disorders of blood,
      metabolic, circulatory and neoplasm, and also discussed their associated
      molecules or genes responsible for the cause of these disorders. Although
      studying Arab-specific genetic disorders resulted in a high value knowledge base,
      approximately 35% of genetic diseases in Arabs do not have a defined molecular
      etiology. This is a clear indication that comprehensive research is required in
      this area to understand the molecular pathologies causing diseases in Arab
      populations. 

PMID- 25780795
TI  - Bioresorbable scaffolds for percutaneous coronary interventions.
AB  - Innovations in drug-eluting stents (DES) have substantially reduced rates of in
      segment restenosis and early stent thrombosis, improving clinical outcomes
      following percutaneous coronary interventions (PCI). However a fixed metallic
      implant in a vessel wall with restored patency and residual disease remains a
      precipitating factor for sustained local inflammation, in-stent neo
      atherosclerosis and impaired vasomotor function increasing the risk for late
      complications attributed to late or very late stent thrombosis and late target
      lesion revascularization (TLR) (late catch-up). The quest for optimal coronary
      stenting continues by further innovations in stent design and by using
      biocompatible materials other than cobalt chromium, platinum chromium or
      stainless steel for engineering coronary implants. Bioresorbable scaffolds made
      of biodegradable polymers or biocorrodible metals with properties of transient
      vessel scaffolding, local drug-elution and future restoration of vessel anatomy,
      physiology and local hemodynamics have been recently developed. These devices
      have been utilized in selected clinical applications so far providing preliminary
      evidence of safety showing comparable performance with current generation drug
      eluting stents (DES). Herein we provide a comprehensive overview of the current
      status of these technologies, we elaborate on the potential benefits of transient
      coronary scaffolds over permanent stents in the context of vascular reparation
      therapy, and we further focus on the evolving challenges these devices have to
      overcome to compete with current generation DES. CONDENSED ABSTRACT: : The quest
      for optimizing percutaneous coronary interventions continues by iterative
      innovations in device materials beyond cobalt chromium, platinum chromium or
      stainless steel for engineering coronary implants. Bioresorbable scaffolds made
      of biodegradable polymers or biocorrodible metals with properties of transient
      vessel scaffolding; local drug-elution and future restoration of vessel anatomy,
      physiology and local hemodynamics were recently developed. These devices have
      been utilized in selected clinical applications providing preliminary evidence of
      safety showing comparable intermediate term clinical outcomes with current
      generation drug-eluting stents.

PMID- 25780796
TI  - Computational fluid dynamics applied to virtually deployed drug-eluting coronary
      bioresorbable scaffolds: Clinical translations derived from a proof-of-concept.
AB  - BACKGROUND: Three-dimensional design simulations of coronary metallic stents
      utilizing mathematical and computational algorithms have emerged as important
      tools for understanding biomechanical stent properties, predicting the
      interaction of the implanted platform with the adjacent tissue, and informing
      stent design enhancements. Herein, we demonstrate the hemodynamic implications
      following virtual implantation of bioresorbable scaffolds using finite element
      methods and advanced computational fluid dynamics (CFD) simulations to visualize
      the device-flow interaction immediately after implantation and following scaffold
      resorption over time. METHODS AND RESULTS: CFD simulations with time averaged
      wall shear stress (WSS) quantification following virtual bioresorbable scaffold
      deployment in idealized straight and curved geometries were performed. WSS was
      calculated at the inflow, endoluminal surface (top surface of the strut), and
      outflow of each strut surface post-procedure (stage I) and at a time point when
      33% of scaffold resorption has occurred (stage II). The average WSS at stage I
      over the inflow and outflow surfaces was 3.2 and 3.1 dynes/cm(2) respectively and
      87.5 dynes/cm(2) over endoluminal strut surface in the straight vessel. From
      stage I to stage II, WSS increased by 100% and 142% over the inflow and outflow
      surfaces, respectively, and decreased by 27% over the endoluminal strut surface.
      In a curved vessel, WSS change became more evident in the inner curvature with an
      increase of 63% over the inflow and 66% over the outflow strut surfaces. Similar
      analysis at the proximal and distal edges demonstrated a large increase of 486%
      at the lateral outflow surface of the proximal scaffold edge. CONCLUSIONS: The
      implementation of CFD simulations over virtually deployed bioresorbable scaffolds
      demonstrates the transient nature of device/flow interactions as the
      bioresorption process progresses over time. Such hemodynamic device modeling is
      expected to guide future bioresorbable scaffold design.

PMID- 25780797
TI  - Radiation in medicine: Origins, risks and aspirations.
AB  - The use of radiation in medicine is now pervasive and routine. From their crude
      beginnings 100 years ago, diagnostic radiology, nuclear medicine and radiation
      therapy have all evolved into advanced techniques, and are regarded as essential
      tools across all branches and specialties of medicine. The inherent properties of
      ionizing radiation provide many benefits, but can also cause potential harm. Its
      use within medical practice thus involves an informed judgment regarding the
      risk/benefit ratio. This judgment requires not only medical knowledge, but also
      an understanding of radiation itself. This work provides a global perspective on
      radiation risks, exposure and mitigation strategies. 

PMID- 25780798
TI  - Voltage-gated sodium channels in the mammalian heart.
AB  - Mammalian species express nine functional voltage-gated Na(+) channels. Three of
      them, the cardiac-specific isoform Nav1.5 and the neuronal isoforms Nav1.8 and
      Nav1.9, are relatively resistant to the neurotoxin tetrodotoxin (TTX; IC50 >= 1
      MUM). The other six isoforms are highly sensitive to TTX with IC50 values in the
      nanomolar range. These isoforms are expressed in the central nervous system
      (Nav1.1, Nav1.2, Nav1.3, Nav1.6), in the skeletal muscle (Nav1.4), and in the
      peripheral nervous system (Nav1.6, Nav1.7). The isoform Nav1.5, encoded by the
      SCN5A gene, is responsible for the upstroke of the action potential in the heart.
      Mutations in SCN5A are associated with a variety of life-threatening arrhythmias,
      like long QT syndrome type 3 (LQT3), Brugada syndrome (BrS) or cardiac conduction
      disease (CCD). Previous immunohistochemical and electrophysiological assays
      demonstrated the cardiac expression of neuronal and skeletal muscle Na(+)
      channels in the heart of various mammals, which led to far-reaching speculations
      on their function. However, when comparing the Na(+) channel mRNA patterns in the
      heart of various mammalian species, only minute quantities of transcripts for TTX
      sensitive Na(+) channels were detectable in whole pig and human hearts,
      suggesting that these channels are not involved in cardiac excitation phenomena
      in higher mammals. This conclusion is strongly supported by the fact that
      mutations in TTX-sensitive Na(+) channels were associated with epilepsy or
      skeletal muscle diseases, rather than with a pathological cardiac phenotype.
      Moreover, previous data from TTX-intoxicated animals and from cases of human
      tetrodotoxication showed that low TTX dosages caused at most little alterations
      of both the cardiac output and the electrocardiogram. Recently, genome-wide
      association studies identified SCN10A, the gene encoding Nav1.8, as a determinant
      of cardiac conduction parameters, and mutations in SCN10A have been associated
      with BrS. These novel findings opened a fascinating new research area in the
      cardiac ion channel field, and the on-going debate on how SCN10A/Nav1.8 affects
      cardiac conduction is very exciting. 

PMID- 25780799
TI  - Is susceptibility to chronic rheumatic heart disease determined in early infancy?
      An analysis of mortality in Britain during the 20th century.
AB  - BACKGROUND: The reason why some individuals but not others are susceptible to
      rheumatic fever and chronic rheumatic heart disease is not understood. Because of
      the substantial evidence that poverty is an important determinant of the disease
      and must operate in early life, we have investigated the role of the early
      environment in an ecological study using 20(th) century mortality as an index of
      disease prevalence. METHODS: We analysed 37,321 deaths from rheumatic heart
      disease in England and Wales during 1968-78. We compared the geographical
      distribution of deaths with previous infant mortality records from 1911 onwards.
      These records included details of mortality at different ages and from different
      causes. They also included data on housing and population density. RESULTS:
      Mortality from rheumatic heart disease showed a strong correlation with past
      infant mortality that was consistently stronger with postneonatal mortality
      (deaths from one month to one year) than with neonatal mortality (deaths during
      the first month of life). Areas with high infant mortality from diarrhoea or
      bronchitis had the highest subsequent mortality from rheumatic heart disease.
      Although rheumatic heart disease was linked with early overcrowding, regression
      analyses suggested that overcrowding could not per se explain the infant
      mortality associations. CONCLUSIONS: Chronic rheumatic heart disease may have its
      origins in early infancy. Our findings raise the possibility that susceptibility
      to rheumatic fever and rheumatic heart disease may be linked with infection in
      the postneonatal period. Alternatively, they may be explained by the operation of
      environmental factors that both predispose to infection in infancy and the
      subsequent liability to heart disease.

PMID- 25780800
TI  - Genetic susceptibility to endomyocardial fibrosis.
AB  - BACKGROUND: Endomyocardial fibrosis (EMF) is the most common form of restrictive
      cardiomyopathy worldwide. It has been linked to poverty and various environmental
      factors, but-for unknown reasons-only some people who live in similar conditions
      develop the disease. EMF cases cluster within both families and ethnic groups,
      suggesting a role for a genetic factor in host susceptibility. The human
      leukocyte antigen (HLA) system is associated with predisposition to various
      diseases. This two-center study was designed to investigate variation in the HLA
      system between EMF patients and unaffected controls. We provide the first genetic
      investigation of patients with EMF, as well as a comprehensive review of the
      literature. METHODS: HLA class I (HLA-A, -B, -C) and class II (DRB1, DQB1) types
      were determined in 71 patients with severe EMF and 137 controls from Uganda and
      Mozambique. Chi Square analysis was used to identify any significant difference
      in frequency of class I and class II HLA types between cases and controls.
      RESULTS: Compared to ethnically matched controls, HLA-B*58 occurred more
      frequently in Mozambique patients with EMF and HLA-A*02:02 occurred more
      frequently in Ugandan patients with EMF. CONCLUSIONS: Ample subjective evidence
      in the historical literature suggests the importance of a genetically susceptible
      host in EMF development. In this first formal genetic study, we found HLA alleles
      associated with cases of EMF in two populations from sub-Saharan Africa, with EMF
      patients being more likely than controls to have the HLA-B*58 allele in
      Mozambique (p-0.03) and the HLA-A*02:02 in Uganda (p = 0.005). Further
      investigations are needed to more fully understand the role of genetics in EMF
      development.

PMID- 25780801
TI  - The time-course of speaking rate compensation: Effects of sentential rate and
      vowel length on voicing judgments.
AB  - Many sources of context information in speech (such as speaking rate) occur
      either before or after the phonetic cues they influence, yet there is little work
      examining the time-course of these effects. Here, we investigate how listeners
      compensate for preceding sentence rate and subsequent vowel length (a secondary
      cue that has been used as a proxy for speaking rate) when categorizing words
      varying in voice-onset time (VOT). Participants selected visual objects in a
      display while their eye-movements were recorded, allowing us to examine when each
      source of information had an effect on lexical processing. We found that the
      effect of VOT preceded that of vowel length, suggesting that each cue is used as
      it becomes available. In a second experiment, we found that, in contrast, the
      effect of preceding sentence rate occurred simultaneously with VOT, suggesting
      that listeners interpret VOT relative to preceding rate.

PMID- 25780802
TI  - AIDS incidence and AIDS-related mortality in British  Columbia, Canada, between
      1981 and 2013: a retrospective  study.
AB  - BACKGROUND: Appropriate use of highly active antiretroviral therapy (ART) can
      substantially decrease the risk of progression to AIDS and of premature
      mortality. We aimed to characterise the trends between 1981 and 2013 in AIDS
      defining illnesses (ADIs) and the number AIDS-related deaths in British Columbia,
      Canada, where ART has been fully subsidised since 1996. METHODS: We included data
      on HIV-positive individuals, aged 19 years or older, from four administrative
      databases in British Columbia: the British Columbia Centre for Excellence in
      HIV/AIDS, St Paul's Hospital, the British Columbia Vital Statistics Agency, the
      British Columbia Cancer Agency. We estimated the relative risk of developing an
      ADI over time by use of a negative binomial model, and we investigated trends in
      the proportion of all deaths associated with AIDS by use of generalised additive
      models. FINDINGS: Data were available for 3550 people with HIV. 6205 ADIs were
      recorded. In 2013, 84 ADIs occurred, the lowest number since 1990. The peak of
      the AIDS epidemic in the region happened in 1994 with 696 ADIs reported (42 ADIs
      per 100 person-years). Since 1997, the number of ADIs decreased from 253 (7 per
      100 person-years) to 84 cases in 2013 (1 per 100 person-years; p<0.0001 for trend
      in number of ADIs). We have also shown that of 22 ADIs included, only
      Pneumocystis jirovecii pneumonia remained prominent (albeit with much reduced
      overall prevalence). 2828 deaths were from AIDS-related causes, peaking in 1996
      with 241 (96%) of 252 deaths in people with HIV and declining to 44 (20%) of 218
      in 2013. INTERPRETATION: Our results provide further evidence that integrated
      comprehensive free programmes that facilitate testing and deliver treatment and
      care can be eff ective in decreasing AIDS-related morbidity and mortality, thus
      suggesting that control of and eventually an end to AIDS are possible.

PMID- 25780803
TI  - Fabrication of silver nanoplate hierarchical turreted ordered array and its
      application in trace analyses.
AB  - Silver nanoplate hierarchical turreted ordered arrays were fabricated through an
      electro-deposition method on ordered acuate silicon nanocone templates. Such
      arrays can be used as SERS substrates for trace analyses of streptomycin
      sulphate, and exhibit high activity and stability. This work is of importance in
      practical applications based on the SERS effect of noble metal micro/nano
      structured arrays. 

PMID- 25780804
TI  - A one-step hydrothermal route to programmable stimuli-responsive hydrogels.
AB  - A hydrothermal route to regulate the swelling and responsiveness properties of
      poly(N-isopropylacrylamide) (PNIPAM) hydrogels is reported. During the process,
      water is the only reactive medium used, and the hydrogel properties can be
      programmed effectively. 

PMID- 25780805
TI  - Development of an electrochemical surface-enhanced Raman spectroscopy (EC-SERS)
      aptasensor for direct detection of DNA hybridization.
AB  - Rapid detection of disease biomarkers at the patient point-of-care is essential
      to timely and effective treatment. The research described herein focuses on the
      development of an electrochemical surface-enhanced Raman spectroscopy (EC-SERS)
      DNA aptasensor capable of direct detection of tuberculosis (TB) DNA.
      Specifically, a plausible DNA biomarker present in TB patient urine was chosen as
      the model target for detection. Cost-effective screen printed electrodes (SPEs)
      modified with silver nanoparticles (AgNP) were used as the aptasensor platform,
      onto which the aptamer specific for the target DNA was immobilized. Direct
      detection of the target DNA was demonstrated through the appearance of SERS peaks
      characteristic for adenine, present only in the target strand. Modulation of the
      applied potential allowed for a sizeable increase in the observed SERS response
      and the use of thiol back-filling prevented non-specific adsorption of non-target
      DNA. To our knowledge, this work represents the first EC-SERS study of an
      aptasensor for the direct, label-free detection of DNA hybridization. Such a
      technology paves the way for rapid detection of disease biomarkers at the patient
      point-of-care. 

PMID- 25780806
TI  - Enhancement and extinction effects in surface-enhanced stimulated Raman
      spectroscopy.
AB  - We address the optical physics of surface-enhanced stimulated Raman spectroscopy
      (SESRS) from the microscopic to macroscopic scales to provide experimental design
      criteria in colloidal-suspension SESRS. The nanoparticles that provide local
      field enhancement also extinguish the Raman signal. We compute the total Raman
      signal detected from a suspension of Raman-active molecules and nanoparticles due
      to the cumulative effects of enhancement and extinction and find optimum
      operating parameters for pump frequency and nanoparticle concentration. 

PMID- 25780807
TI  - Reply: To PMID 22618564.

PMID- 25780808
TI  - Goodbye my friend (Carlos E. Baena-Cagnani).

PMID- 25780809
TI  - Nitric oxide signals postovulatory aging-induced abortive spontaneous egg
      activation in rats.
AB  - OBJECTIVE: The aim of this study was to determine whether an increase of
      intracellular nitric oxide (NO) level signals postovulatory aging-induced
      abortive spontaneous egg activation (SEA) in rats. METHODS: Freshly ovulated eggs
      (arrested at metaphase-II stage; M-II) were cultured in vitro for 3 hours to
      induce postovulatory egg aging. The morphological changes, inducible nitric oxide
      synthase (iNOS) expression, NO, cytosolic free Ca(2+), 3',5' cyclic guanosine
      monophosphate (cGMP), cell division cycle 25B (Cdc25B) and Wee1 levels, specific
      phosphorylation (pThr-14/Tyr-15) as well as total cyclin-dependent kinases-1
      (Cdk1) (PSTAIRE) levels were analyzed. RESULTS: Postovulatory aging induced
      generation of NO possibly through an iNOS-mediated pathway. The increase in NO
      level was associated with augmented cytosolic free Ca(2+) as well as cGMP levels
      in aged eggs. A significant increase in Wee1 level and decrease of Cdc25B level
      were observed in aged eggs. An accumulation of phosphorylated Cdk1 (pThr-14/Tyr
      15) level was observed in aged eggs, while total Cdk1 (PSTAIR) level remained
      unchanged. CONCLUSION: Our study demonstrates that generation of NO through an
      iNOS-mediated pathway increases cytosolic free Ca2+and cGMP levels. High levels
      of these signal molecules trigger the accumulation of phosphorylated Cdk1 in aged
      eggs. Thus, NO signals the accumulation of phosphorylated Cdk1 and induces
      postovulatory aging-induced abortive SEA in the rat.

PMID- 25780810
TI  - Effects of dietary betaine on growth performance, fat deposition and serum lipids
      in broilers subjected to chronic heat stress.
AB  - We evaluated the effects of supplementing betaine on growth performance, fat
      deposition and lipid metabolism status in broilers kept under chronic heat
      stress. Five hundred and forty chicks were randomly divided into six groups and
      the two normal temperature groups were held at normal ambient temperature and fed
      the basal diet (CONT) and basal diet plus 0.1% betaine, respectively. Heat
      stressed (HS) broilers were held at 32 +/- 1 degrees C from days 22 to 42 and fed
      the basal diet containing variable levels of betaine. Broilers were examined at
      days 28, 35 and 42 for body weight, feed consumption, fat deposition and serum
      lipids. The CONT and betaine-supplemented groups showed higher (P < 0.01 or P <
      0.05) feed consumption, body weight gain, and lower feed : gain ratio compared
      with the HS-CONT group. Meanwhile, heat stress increased abdominal, intermuscular
      and subcutaneous fat deposition, whereas the supplemental betaine significantly
      decreased those compared with the HS-CONT group. Additionally, betaine
      supplementation significantly decreased triglyceride, free fatty acids, low
      density lipoprotein cholesterol and high-density lipoprotein cholesterol compared
      with HS-CONT. Chronic HS reduces broiler production performance. However, betaine
      can reverse these negative effects partially and thus improve carcass composition
      by changing lipid metabolism. 

PMID- 25780811
TI  - Children born to women treated for hypothyroidism during pregnancy show abnormal
      corpus callosum development.
AB  - BACKGROUND: Thyroid hormone (TH) is essential for the developing brain, and
      because the fetal thyroid develops relatively late in gestation, the maternal TH
      supply is critical for fetal brain development. However, if the mother has
      hypothyroidism during pregnancy, fetal brain and neuropsychological development
      may be compromised. Rodents experiencing maternal TH insufficiency show abnormal
      corpus callosum (CC) morphology, but it is not known if children born to women
      treated for hypothyroidism (HYPO) show similar effects. The purpose of the
      current study was to investigate HYPO for CC morphology and morphometry and to
      determine whether any specific CC abnormalities were associated aspects of
      maternal hypothyroidism and were correlated with reduced neuropsychological
      functioning in the children. METHODS: ANALYZE software was used to trace CCs in
      archived magnetic resonance imaging scans from 22 HYPO and 22 matched controls.
      Areas of two sub-regions and six segments and different shape metrics (angles,
      lengths, ratios) were determined. CC parameters were correlated with maternal
      thyrotropin (TSH) values and number of hypothyroid trimesters as well as the
      child's neuropsychological test performance. RESULTS: HYPO showed a smaller
      anterior CC and genu and larger posterior CC and splenium areas than controls as
      well as shape abnormalities in genu and splenium. Results were correlated with
      the duration of maternal hypothyroidism. Executive function skills were
      positively associated with genu size in HYPO, while verbal comprehension skills
      were negatively associated with splenium and overall posterior CC sizes.
      CONCLUSIONS: Maternal hypothyroidism contributes to CC abnormalities in the
      offspring, and effects differ for anterior versus posterior CC regions.

PMID- 25780812
TI  - Polymorphism at the Clock gene predicts phenology of long-distance migration in
      birds.
AB  - Dissecting phenotypic variance in life history traits into its genetic and
      environmental components is at the focus of evolutionary studies and of pivotal
      importance to identify the mechanisms and predict the consequences of human
      driven environmental change. The timing of recurrent life history events
      (phenology) is under strong selection, but the study of the genes that control
      potential environmental canalization in phenological traits is at its infancy.
      Candidate genes for circadian behaviour entrained by photoperiod have been
      screened as potential controllers of phenological variation of breeding and moult
      in birds, with inconsistent results. Despite photoperiodic control of migration
      is well established, no study has reported on migration phenology in relation to
      polymorphism at candidate genes in birds. We analysed variation in spring
      migration dates within four trans-Saharan migratory species (Luscinia
      megarhynchos; Ficedula hypoleuca; Anthus trivialis; Saxicola rubetra) at a
      Mediterranean island in relation to Clock and Adcyap1 polymorphism. Individuals
      with larger number of glutamine residues in the poly-Q region of Clock gene
      migrated significantly later in one or, respectively, two species depending on
      sex and whether the within-individual mean length or the length of the longer
      Clock allele was considered. The results hinted at dominance of the longer Clock
      allele. No significant evidence for migration date to covary with Adcyap1
      polymorphism emerged. This is the first evidence that migration phenology is
      associated with Clock in birds. This finding is important for evolutionary
      studies of migration and sheds light on the mechanisms that drive bird
      phenological changes and population trends in response to climate change. 

PMID- 25780813
TI  - Post-partum anemia and factors that work against alleviation of the anemia.
AB  - AIM: This study aimed to clarify conditions of women experiencing post-partum
      anemia and identify factors that work against the alleviation of anemia. METHODS:
      This was a retrospective longitudinal study, involving 246 women giving birth at
      five participating institutions, diagnosed with anemia on day 3 post-partum, and
      given a blood sample at the medical examination 1 month after the birth. With
      answers about alleviation of anemia during the 1 month post-partum period as an
      objective variable, and explanatory variables, multiple logistic regression
      analysis was performed. The explanatory variables included demographic data of
      the participants, information about anemia, following the nutrition instruction
      advice for anemia alleviation, family structure and others assisting the
      participants, and self-management skills (measured by the Self-Management Skill
      [SMS] scale). RESULTS: The present authors collected 211 valid responses; the
      average age was 32.6 years. The mean hemoglobin values on the 3rd and 30th days
      post-partum were 9.6 and 12.0 g/dL, respectively. One fifth of the participants
      (21.3%) showed no anemia alleviation. The mean value on the SMS scale was 28.35,
      and the anemia alleviated group (30.78) was significantly higher than the non
      alleviated group (19.38). Results of the multiple logistic regression analysis
      showed a strong relationship between anemia risk and self-management skills. The
      absence of anemia alleviation increased 2.51 times as the total score of the SMS
      decreased 1 point. CONCLUSION: There is an urgent need to develop an intervention
      program to alleviate post-partum anemia focusing on the low score items because
      self-management skills strongly affect alleviation improvement.

PMID- 25780815
TI  - Convergent Strategies in Total Syntheses of Complex Terpenoids.

PMID- 25780814
TI  - Eating disorders and biochemical composition of saliva: a retrospective matched
      case-control study.
AB  - This study aimed to compare the biochemical composition of saliva from patients
      with eating disorders (EDs) with saliva from control subjects with no ED. All
      patients who initiated outpatient treatment in an ED clinic during a 12-month
      period were invited to participate. Of the 65 patients who started treatment
      during the period, 54 (50 female patients/four male patients; mean age: 21.5 yr)
      agreed to participate. The controls were 54 sex- and age-matched patients from a
      dental health clinic. All participants completed a questionnaire and underwent
      dental clinical examinations, including laboratory analyses of saliva. The
      proportion of subjects with unstimulated salivary hyposalivation was lower in the
      ED group and not correlated with intake of xerogenic drugs. Significant
      differences in the biochemical composition of saliva were found almost
      exclusively in the unstimulated state, with albumin, inorganic phosphate,
      aspartate aminotransferase (ASAT), chloride, magnesium, and total protein all
      being significantly higher in the ED group. Conditional logistic regression
      showed that higher ASAT and total protein concentrations were relatively good
      predictors of ED, with sensitivity and specificity of 65% and 67%, respectively.
      In conclusion, elevated salivary concentrations of ASAT and total protein may
      serve as indicators of ED as well as of disease severity. Future studies are
      needed to corroborate these initial findings.

PMID- 25780816
TI  - Viscoelastic properties of electrochemically deposited protein/metal complexes.
AB  - The interfacial gelation of proteins at metallic surfaces was investigated with
      an electrochemical quartz crystal microbalance (QCM). When Cr electrodes were
      corroded in proteinaceous solutions, it was found that gels will form at the Cr
      surfaces if molybdate ions are also present in the solution. Gelation is
      reversible and can also be controlled with the electrochemical potential at the
      electrode. Further, a method was developed to characterize the viscoelastic
      properties of thin films in liquid media using the QCM as a high-frequency
      rheometer. By measuring the frequency and dissipation at multiple harmonics of
      the resonance frequency, the viscoelastic phase angle, density-modulus product,
      and areal mass of a film can be determined. The method was applied to
      characterize the protein films, demonstrating that they have a phase angle near
      55 degrees  and a density-modulus product of ~10(7) Pa.g/cm(3). Data imply that
      the gels are composed of a weakly cross-linked proteinaceous network with
      properties similar to albumin solutions with concentrations in the range of ~40
      wt %. 

PMID- 25780817
TI  - Acrodermatitis Enteropathica: A Novel SLC39A4 Gene Mutation in a Patient with
      Normal Zinc Levels.
AB  - Acrodermatitis enteropathica (AE) is a rare disease that results from a defective
      gene, SLC39A4, and is characterized by dermatitis, alopecia, and diarrhea. We
      report a case of AE presenting with only periorificial and acral dermatitis in
      which genetic testing revealed two novel compound heterozygous missense mutations
      for SLC39A4. This case demonstrates that not all AE mutations alter zinc
      transporters in the same manner and highlights the phenotypic variability of AE. 

PMID- 25780818
TI  - Small rodents as reservoirs of Cryptosporidium spp. and Giardia spp. in south
      western Poland.
AB  - Cryptosporidium spp. and Giardia spp. have been detected in a range of host
      species, including rodents. The aim of this study was to determine the
      distribution of these pathogens and recognition of the reservoir role of rodents
      in the maintenance of these pathogens in south-western Poland. Additionally,
      preliminary molecular studies were conducted to elucidate the species and
      genotypes of Cryptosporidium and Giardia identified in this study. Stool samples
      (n=266) from A. agrarius, A. flavicollis and M. glareolus, were subjected for
      analyses. Values of prevalence were 61.7, 68.3 and 68.1%, respectively, for
      Cryptosporidium spp. and 41.7, 24.4 and 38.4%, respectively, for Giardia spp.
      There was a statistically significant correlation between host species and
      Giardia infection where A. agrarius was the species of the highest prevalence.
      Statistically significant differences were not found for comparisons made for
      study sites and occurrence of Giardia spp. and Cryptosporidium spp. Due to
      preliminary nested PCR results, specific amplifications of Cryptosporidium COWP
      and SSU rRNA genes were obtained for several isolates taken from rodent host
      species. One isolate recovered from A. agrarius (from a semi-aquatic, urban area)
      was identified as C. parvum and revealed 100% similarity with sequences obtained
      from humans. To the best of the knowledge of the authors, this is the first
      record of the C. parvum zoonotic species from the striped field mouse. Also
      recorded were the first findings of C. ubiquitum from three small rodent species.

PMID- 25780819
TI  - Seasonal variation of Ganoderma spore concentrations in urban and suburban
      districts of the city of Szczecin, Poland.
AB  - According to recent studies, Ganoderma may be the third genus, after Alternaria
      and Cladosporium, the spores of which cause symptoms of allergy, and
      concentration is related to meteorological factors. The aerobiology of Ganoderma
      spores in Szczecin in urban and suburban districts was examined using Lanzoni
      Volumetric Spore Traps in 2008-2010. Ganoderma spores were present in the
      atmosphere on more than 90% of the days from June through September with peak
      concentrations in June, July and September. The number of days with spores was
      lower in the suburban district, while the total number of spores collected was
      higher there than in the urban district. Correlation and multiple regression
      analyses revealed weak relationships between Ganoderma and meteorological
      conditions, while testing the significance of differences between the districts
      showed that urban development did not have a clear impact on the values of
      meteorological parameters. A significantly higher abundance of spores in the
      suburbs of Szczecin seemed to be conditioned by the closeness of potential area
      sources. This study indicates that a single measuring site in the city centre
      insufficiently reflected the dynamics and level of Ganoderma spore concentration
      in peripheral districts. 

PMID- 25780820
TI  - Serological and molecular evidence of hepadnavirus infection in swine.
AB  - INTRODUCTION AND OBJECTIVE: Recently, investigations in a swine herd identified
      evidence of the existence of a novel member of the Hepadnavirus family endemic in
      swine. The aim of this study was to investigate the serological and molecular
      markers of Hepadnavirus circulation in Brazilian domestic swine and wild boar
      herds, and to evaluate the identity with HBV and other Hepadnaviruses reported
      previously. MATERIALS AND METHODS: For the study, 376 swine were screened for
      hepatitis B virus serological markers. Analyses were performed in serum samples
      using commercial enzyme-linked immunosorbent assay (ELISA) kits (DiaSorin(r)) for
      anti-HBc, HBsAg and anti-HBs. Reactive and undetermined swine serum samples were
      selected to perform DNA viral extraction (QIAamp DNA Mini Kit, Qiagen(r)),
      partial genome amplification and genome sequencing. RESULTS: From 376 swine
      samples analysed, 28 (7.45%) were reactive to anti-HBc, 3 (0.80%) to HBsAg and 6
      (1.6%) to anti-HBs. Besides, more 17 (4.52%) swine samples analyzed were
      classified in the grey zone of the EIA test to anti-HBc and 2 (0.53%) to HBsAg.
      From 49 samples molecularly analyzed after serological trial, 4 samples showed a
      positive result for the qualitative PCR for Hepadnavirus. Phylogenetic
      reconstruction using partial genome sequencing (360 bp) of 3 samples showed
      similarity with HBV with 90.8-96.3% of identity. CONCLUSIONS: Serological and
      molecular data showed evidence of the circulation of a virus similar to hepatitis
      B virus in swine.

PMID- 25780821
TI  - Child car seats - a habitat for house dust mites and reservoir for harmful
      allergens.
AB  - INTRODUCTION AND OBJECTIVE: House dust mites produce allergens which can cause or
      aggravate diseases such as asthma, eczema and rhinitis. The objectives of this
      study are to quantify typical house dust mite and Der p 1 allergen levels in
      child car seats, and to determine external variables that may influence mite
      populations in cars. MATERIALS AND METHODS: Dust samples were collected from the
      child car seats and driver seats of 106 cars using a portable vacuum sampling
      pump over a two minute sampling period. Mites were counted and identified and
      results were expressed as mites per gram (mites/g) of dust, while Der p 1 content
      of samples were measured by enzyme-linked immunosorbent assay (ELISA).
      Questionnaires were completed by participants to identify environmental and
      behavioural effects on mite populations. Results were analysed using General
      Linear Model (GLM) procedures. RESULTS: Twelve species of mites, of which nine
      are known to produce harmful allergens, were recorded from 212 dust samples. Over
      80% of drivers' seats and over 77% of child car seats harboured dust mites with a
      significant correlation (p = 0.001) between the mites/g of dust and Der p 1
      content recovered from each seat. A mean of 53 mites/g of dust per seat was
      recovered, with a mean Der p 1 level of 1.1ug/g. Over 12% of driver seats and 15%
      of child car seats contained house dust mite levels sufficient to be risk factors
      for sensitisation and allergic reactions. CONCLUSIONS: Child car seats and driver
      seats are habitats to a range of mite species which can be present in sufficient
      concentrations to cause or aggravate allergen related illnesses in individuals
      who are genetically predisposed.

PMID- 25780822
TI  - Presence of Toxocara spp. eggs in children's recreation areas with varying
      degrees of access for animals.
AB  - INTRODUCTION AND OBJECTIVE: The contamination, seasonal and vertical
      distributions of Toxocara eggs in children's recreation areas were estimated with
      respect to their accessibility to domestic and stray animals. MATERIALS AND
      METHODS: During autumn 2011 and spring 2012, a total 88 composite samples of
      soil/sand (300g each) were taken twice, from 2 depths, from 11 sandpits and 11
      play areas situated in the city of Lodz, Poland. From the collected material, 528
      samples (20g) were tested using the flotation method. Half the sample sites were
      secured from access to dogs and cats, while the other half were not. RESULTS: The
      difference in the numbers of positive samples from sandpits and playing areas was
      significant (c 2 = 13.72, p = 0.0002). The highest rate of contamination was
      observed in poorly-secured play areas (15.8% of positive samples and 1.2 eggs/100
      g of soil/sand). The average density of Toxocara eggs in secured play areas was 6
      times less than that found in unsecured areas, while secured sandpits were 3
      times less contaminated than those unsecured. The contamination rate was similar
      in autumn 2011 and spring 2012 (6.4% and 6.8%, respectively). An inverse
      relationship between the sand/soil depth and number of recovered Toxocara eggs
      was observed. Additionally, other intestinal helminth eggs (Ancylostomidae,
      Ascaris spp., and Trichuris spp.) and oocysts of Isospora spp. were also detected
      from soil samples collected from playing fields. CONCLUSIONS: The number of
      Toxocara eggs recovered decreased following fence construction around the
      examined children's play areas, but it did not sufficiently prevent the
      contamination by eggs. These data indicate the necessity for educational
      programmes which should be implemented for the protection of the local child
      population from zoonotic infection.

PMID- 25780823
TI  - Epidemiology of human toxocariasis in Poland - A review of cases 1978-2009.
AB  - Toxocariasis is a helminthozoonosis due to the infection of humans with larvae
      belonging to the Toxocara genus. Humans become infected as a result of accidental
      consumption of infected eggs containing third stage larvae (L3) nematodes from
      Toxocara canis or Toxocara cati species. Toxocariasis was recognized for the
      first time in the early 1950s, and the first cases of toxocariasis in Poland were
      described a few years later. Toxocariasis is clinically classified into several
      types: classic and incomplete visceral larva migrans (VLM) syndrome, ocular larva
      migrans (OLM) syndrome, neurological toxocariasis (NLM), covert toxocariasis and
      asymptomatic toxocariasis. In 1994-2005, 18,367 sera of people suspected of being
      infected with Toxocara were analysed, 1.8-76% had anti- Toxocara antibodies. In
      the period 1978-2009, 1,022 clinical cases of toxocariasis were recognized in
      Poland. In the opinion of the authors, in order to reduce the frequency of
      toxocariasis in human populations, some prophylaxis should undertaken, e.g.
      public education of zoonotic diseases, systematic control of animal, deworming of
      pets, cleaning pets' faeces by the owners. 

PMID- 25780824
TI  - A study of Neospora caninum and Toxoplasma gondii antibody seroprevalence in
      healthy cattle in the Czech Republic.
AB  - INTRODUCTION AND OBJECTIVE: The aim of study was to test the sera of healthy
      dairy cows by ELISAs, the methods also used in other groups of animals in the
      Czech Republic, and thus to obtain actual data about N. caninum and T. gondii
      seroprevalence in cattle. MATERIAL AND METHODS: In the Czech Republic, sera from
      546 clinically healthy dairy cows (Bos primigenius f. taurus) aged > 2 years from
      49 farms in 7 districts were collected. Sera were tested for Neospora caninum
      antibodies by a commercial competitive-inhibition enzyme-linked immunosorbent
      assay; samples with more than 30% inhibition were considered as positive. The
      same samples were also analysed for Toxoplasma-specific IgG antibodies by an
      enzyme-linked immunosorbent assay; samples with more than 50% S/P were considered
      as positive. RESULTS: Antibodies against N. caninum were found only in 3 cows
      (0.5%) with inhibitions of 47, 78 and 85. Antibodies against T. gondii were found
      in 53 cows (9.7%) with S/P ranging from 51% to over 211%; positive animals were
      found in 4 of 7 districts, with prevalences ranging from 8% - 14%. Indication of
      mixed infections (concurrent presence of both N. caninum and T. gondii
      antibodies) was not proved. CONCLUSION: The results of the study indicate that
      dairy cows in the Czech Republic have a relatively low seroprevalence for both N.
      caninum and T. gondii. Therefore, natural infection with N. caninum and T. gondii
      seems not to be very common in Czech cattle. These results show actual data about
      N. caninum and T. gondii infection in healthy dairy cattle from the Czech
      Republic.

PMID- 25780825
TI  - Occurrence of deoxynivalenol (DON) in wheat flours in Guilan province, northern
      Iran.
AB  - INTRODUCTION AND OBJECTIVE: Deoxynivalenol (DON) is one of several mycotoxins
      produced by certain Fusarium species that frequently infect wheat, corn, rice,
      oats, barley and other grains in the field or during storage. Guilan, Golestan
      and Mazandaran areas are located in the North Iran with favorite conditions for
      Fusarium growth. DON affects animal and human health causing vomiting, acute
      temporary nausea, diarrhea, abdominal pain, headache, dizziness, and fever.
      MATERIALS AND METHODS: In this study, a total of 96 wheat flour samples of
      different types were collected during summer 2013 from six flour mills in
      Northern Iran. All samples were analyzed for DON by enzyme-linked immunosorbent
      assay. RESULTS: DON was detected in 80 out of 96 wheat flour samples (83.33%), at
      levels ranging from 23 to 1270 ug/kg. The maximum contamination level of DON
      (1270 MUg/kg) was found in whole flour while the minimum value (23 MUg/kg) was
      registered in debranned flour. The mean of contamination was 630.53 ug/kg.
      CONCLUSIONS: According to results obtained, incidence and contamination levels of
      DON, seem to be a serious problem for public health. Therefore, cereal and cereal
      based foods should be controlled for the presence of toxins, storage conditions
      and moisture content, which is considered a major factor in the growth of the
      Fusarium fungi.

PMID- 25780826
TI  - Antifungal activity of essential oils against selected terverticillate
      penicillia.
AB  - The aim of this study was to screen 15 essential oils of selected plant species,
      viz. Lavandula angustifolia, Carum carvi, Pinus mungo var. pulmilio, Mentha
      piperita, Chamomilla recutita L., Pinus sylvestris, Satureia hortensis L.,
      Origanum vulgare L., Pimpinella anisum, Rosmarinus officinalis L., Salvia
      officinalis L., Abietis albia etheroleum, Chamomilla recutita L. Rausch, Thymus
      vulgaris L., Origanum vulgare L. for antifungal activity against five Penicillium
      species: Penicillium brevicompactum, Penicillium citrinum, Penicillium crustosum,
      Penicillium expansum and Penicillium griseofulvum. The method used for screening
      included the disc diffusion method. The study points out the wide spectrum of
      antifungal activity of essential oils against Penicillium fungi. There were five
      essential oils of the 15 mentioned above which showed a hopeful antifungal
      activity: Pimpinella anisum, Chamomilla recutita L., Thymus vulgaris, Origanum
      vulgare L. The most hopeful antifungal activity and killing effect against all
      tested penicillia was found to be Origanum vulgare L. and Pimpinella anisum. The
      lowest level of antifungal activity was demonstrated by the oils Pinus mungo var.
      pulmilio, Salvia officinalis L., Abietis albia etheroleum, Chamomilla recutita L.
      Rausch, Rosmarinus officinalis. 

PMID- 25780827
TI  - Zoonotic occupational diseases in forestry workers - Lyme borreliosis, tularemia
      and leptospirosis in Europe.
AB  - INTRODUCTION: Forestry workers and other people who come into close contact with
      wild animals, such as hunters, natural science researchers, game managers or
      mushroom/berry pickers, are at risk of contracting bacterial, parasitological or
      viral zoonotic diseases. Synthetic data on the incidence and prevalence of
      zoonotic diseases in both animals and humans in European forests do not exist. It
      is therefore difficult to promote appropriate preventive measures among workers
      or people who come into direct or indirect contact with forest animals.
      OBJECTIVES: The objectives of this review are to synthesise existing knowledge on
      the prevalence of the three predominant bacterial zoonotic diseases in Europe,
      i.e. Lyme borreliosis, tularemia and leptospirosis, in order to draw up
      recommendations for occupational or public health. METHODS: 88 papers published
      between 1995-2013 (33 on Lyme borreliosis, 30 on tularemia and 25 on
      leptospirosis) were analyzed. CONCLUSIONS: The prevalences of these three
      zoonotic diseases are not negligible and information targeting the public is
      needed. Moreover, the results highlight the lack of standardised surveys among
      different European countries. It was also noted that epidemiological data on
      leptospirosis are very scarce.

PMID- 25780828
TI  - First report of two asymptomatic cases of human infection with Babesia microti
      (Franca, 1910) in Poland.
AB  - Human infection by Babesia microti has been recognized as an emerging zoonosis
      with important public health implications worldwide. In Europe the reported cases
      of human babesiosis have been attributed mostly to B. divergens infection, with
      only sporadic cases of the disease caused by B. microti or B. venatorum. This
      study, based on molecular methods (PCR, R-T PCR, DNA sequencing and phylogenetic
      analysis), reveals for the first time in Poland, asymptomatic infection with .
      microti in immunocompetent healthy individuals working in forest ecosystems. Of
      the 58 professional foresters examined, two (3.4%) were identified as B. microti
      positive by specific PCR. The results of this study also provide strong evidence
      that in eastern Poland, where tick-borne diseases (TBDs) are endemic, there is a
      potential risk of acquiring human babesiosis due to zoonotic B. microti parasites
      commonly found in rodents and I. ricinus ticks. The potential public health
      importance of this finding is discussed. 

PMID- 25780829
TI  - Odour annoyance in the neighbourhood of livestock farming - perceived health and
      health care seeking behaviour.
AB  - INTRODUCTION AND OBJECTIVES: Odour annoyance forms the main source of
      environmental stress in residents living in the proximity of animal feeding
      operations (AFOs) and it has been associated with reduced health. This study aims
      to gain more insight into the association between AFOs in the neighbourhood,
      odour annoyance, other environmental stressors, and health, and incorporates
      health care seeking behaviour for reported symptoms. MATERIALS AND METHODS: Cross
      sectional data from 753 people living in an area in the Netherlands with a high
      density of AFOs was evaluated. Odour and other environmental annoyances in the
      neighbourhood, general health and symptom reporting were obtained by
      questionnaire. Health care utilisation was obtained from electronic medical
      records of general practices. The number of pigs, poultry and cattle within a 500
      m radius from homes was computed using Geographic Information System data.
      Mutually adjusted multiple Poisson and (ordinal) logistic regression analyses
      were performed. RESULTS: The number of pigs, poultry and cattle was equally
      associated with odour annoyance. This annoyance was associated with reduced
      general health and increased reporting of respiratory, gastrointestinal,
      neurological and stress-related symptoms. Participants rarely consulted their
      general practitioner for reported symptoms. Environmental stressors were weakly
      associated. CONCLUSIONS: The number of animals around the homes was associated
      with odour annoyance. Odour annoyance was associated with reduced health, which
      could be a reason for caution with the construction of new AFOs.

PMID- 25780830
TI  - Toxoplasma gondii in small ruminants in Northern Italy - prevalence and risk
      factors.
AB  - OBJECTIVE: The aim of the survey was to evaluate Toxoplasma gondii seroprevalence
      in small ruminants and possible risk factors associated with the infection.
      MATERIALS AND METHODS: Sera from 474 goats and 502 sheep reared on 42 farms in
      northern Italy were collected and tested for IgG antibodies to T. gondii by IFAT
      (indirect immunofluorescence antibody test). To identify risk factors, a binary
      logistic regression analysis of the variables was performed. An audit form about
      farm management was used. RESULTS: Antibodies to T. gondii were found in 96.6% of
      goat farms and in 87.5% of sheep farms; 41.7% goats and 59.3% sheep resulted
      positive. Seroprevalence was significantly higher in sheep than in goats.
      Seroprevalence values were similar in goats from eastern and western areas,
      whereas goats from the southern area were at lower risk of infection. Saanen
      goats presented the lowest seroprevalence (30.7 %), whereas cross-breed exhibited
      the highest rate (48.7%). Goats from farms housing both sheep and goats had an
      infection risk 1.39 times higher than goats from farms that did not house sheep.
      Animals bred on intensive farms showed lower prevalence (22.1%) in comparison
      with those from extensive (45.6%) or semi-intensive farms (60%). Sampling area
      was one of the strongest predictors of T. gondii infection in sheep flocks.
      Transhumant flocks showed a higher risk of infection by T. gondii compared with
      semi-intensive farms (66.8% vs. 38.4%). CONCLUSIONS: The highest T. gondii
      seroprevalence values were registered in transhumant flocks of sheep and in
      family businesses rearing goats. As these traditional activities represent an
      important resource for the conservation of the territory and its economy,
      management practices for a better control of the disease should be improved.

PMID- 25780831
TI  - Age influence on mice lung tissue response to Aspergillus fumigatus chronic
      exposure.
AB  - INTRODUCTION AND OBJECTIVE: Exposure to conidia of Aspergillus fumigatus was
      described as a causative factor of a number of the respiratory system diseases,
      including asthma, chronic eosinophilic pneumonia, hypersensitivity pneumonitis
      and bronchopulmonary aspergillosis. The study investigates the effects of the
      repeated exposure to A. fumigatus in mice pulmonary compartment. Our work tackles
      two, so far insufficiently addressed, important aspects of interaction between
      affected organism and A. fumigatus: 1) recurrent character of exposure
      (characteristic for pathomechanism of the abovementioned disease states) and 2)
      impact of aging, potentially important for the differentiation response to an
      antigen. MATERIALS AND METHODS: In order to dissect alterations of the immune
      system involved with both aging and chronic exposure to A. fumigatus, we used 3-
      and 18-month-old C57BL/6J mice exposed to repeated A. fumigatus inhalations for 7
      and 28 days. Changes in lung tissue were monitored by histological and
      biochemical evaluation. Concentration of pro- and anti-inflammatory cytokines in
      lung homogenates was assessed by ELISA tests. RESULTS AND CONCLUSIONS: Our study
      demonstrated that chronic inflammation in pulmonary compartment, characterized by
      the significant increase of proinflammatory cytokines (IL1, IL6, IL10) levels,
      was the dominant feature of mice response to repeated A. fumigatus inhalations.
      The pattern of cytokines' profile in the course of exposure was similar in both
      age groups, however in old mice the growth of the cytokines' levels was more
      pronounced (especially in case of IL1).

PMID- 25780832
TI  - Epidemiology of animal bites and other potential rabies exposures and anti-rabies
      vaccine utilization in a rural area in Southern Ethiopia.
AB  - The presented report describes the epidemiology of potential rabies exposures and
      examines the utilization of anti-rabies vaccine in a rural area of Ethiopia
      during a period of 43 months. A total of 683 persons (51.1% females, 73%
      children) with animal- related bites were included in the retrospective, registry
      based study. The most common site of exposure was the leg (66.8%). In children
      under 8 years of age the face was more often involved than in adults (9.5% vs.
      4.8%; p=0.03). The main type of exposure was a bite with bleeding (66.3%)
      followed by contamination of mucous membranes with saliva (19.7%). The primary
      sources were dogs (93.4%) followed by cats (2.6%). Children under 15 years were
      more likely to be exposed to dogs (94.9%) than adults (88.7%) (p=0.01). The most
      common way of coming in contact with animals was 'walking by' (83.9%). Children
      came in contact with animals while 'playing with' (10.7%) more often than adults
      (1.1%) (p<0.001). All the patients received an anti-rabies nervous-tissue
      vaccine, 99% of whom completed the vaccination course. Animal bites continue to
      be a problem in rural Ethiopia, mainly among children. Efforts to protect
      children against animal bites must be of paramount importance in preventing
      rabies in this population. 

PMID- 25780833
TI  - Detection of protozoans Babesia microti and Toxoplasma gondii and their co
      existence in ticks (Acari: Ixodida) collected in Tarnogorski district (Upper
      Silesia, Poland).
AB  - INTRODUCTION: Ticks (Acari: Ixodida) are vectors of many pathogens i. a: Babesia
      microti [Bm] and Toxoplasma gondii [Tg]. In Poland, Ixodes ricinus [Ir] is the
      main vector of both pathogens. This tick species and pathogens transmitted by
      them are a significant threat to human and animal health. OBJECTIVES OF THE
      STUDY: Detection of the protozoans Bm and Tg in ticks collected in the
      Tarnogorski district area. MATERIAL AND METHODS: The ticks were collected from
      vegetation and pets in the spring period of their activity on the territory of
      the Tarnogorski district. The parasites were preserved in 70% ethanol. DNA was
      isolated by ammonia method. Bm was detected by nested-PCR using specific primers
      for the 18S rRNA sequence. To detect the Tg a commercial kit was used. The PCR
      products were separated on 2% ethidium bromide stained agarose gels and
      visualised under UV light. RESULTS: It was showed that all collected ticks
      belonged to the species Ir. Bm was detected in 50.87% and Tg in 64.91% of all
      examined ticks. Co-existence of these both protozoans in 36.84% of total examined
      ticks was noted. CONCLUSIONS: The study showed a high risk of exposure to Bm and
      Tg in the studied area. Ticks Ir play an important role in the transmission of Bm
      in this region. Demonstrating a high percentage of ticks collected from animals
      infected with Tg may indicate their important role in the transmission of this
      pathogen, but it requires a further studies.

PMID- 25780834
TI  - One-step synthesis of highly-biocompatible spherical gold nanoparticles using
      Artocarpus heterophyllus Lam. (jackfruit) fruit extract and its effect on
      pathogens.
AB  - INTRODUCTION: Novel approaches for the synthesis of gold nanoparticles (AuNPs)
      are of great importance due to its vast spectrum of applications in diverse
      fields, including medical diagnostics and therapeutics. Te presented study
      reports the successful AuNPs' synthesis using Artocarpus heterophyllus Lam.
      extract, and provides detailed characterization and evaluation of its
      antibacterial potential. OBJECTIVE: The aim was to develop a cost-effective and
      environmentally friendly synthesis method of gold nanoparticles using aqueous
      fruit extract of Artocarpus heterophyllus Lam. as a reducing and capping agent,
      which has proven activity against human pathogens, such as microbial species
      E.coli and Streptobacillus sps. MATERIALS AND METHOD: Characterizations were
      carried out using ultraviolet-visible (UV-Vis) spectrophotometry, scanning
      electron microscopy (SEM), energy dispersive X-ray and Fourier-Transform infra
      red spectroscopy (FT-IR). RESULTS: SEM images showed the formation of gold
      nanoparticles with an average size of 20-25 nm. Spectra collected while infra-red
      analysis contained broad peaks in ranges from 4000-400 cm -1 . CONCLUSIONS: It
      can be concluded that the fruit of Artocarpus heterophyllus Lam. can be good
      source for synthesis of gold nanoparticles which showed antimicrobial activity
      against investigated microbes, in particul E. coli, and Streptobacillus. An
      important outcome of this study will be the development of value-added products
      from the medicinal plant Artocarpus heterophyllus Lam. for the biomedical and
      nanotechnology-based industries.

PMID- 25780835
TI  - Central auditory processing disorder (CAPD) tests in a school-age hearing
      screening programme - analysis of 76,429 children.
AB  - INTRODUCTION AND OBJECTIVE: Hearing disorders among school-age children are a
      current concern. Continuing studies have been performed in Poland since 2008, and
      on 2 December 2011 the EU Council adopted Conclusions on the Early Detection and
      Treatment of Communication Disorders in Children, Including the Use of e-Health
      Tools and innovative Solutions. The discussion now focuses not only on the
      efficacy of hearing screening programmes in schoolchildren, but what should be
      its general aim and what tests it should include? This paper makes the case that
      it is important to include central auditory processing disorder (CAPD) tests. One
      such test is the dichotic digits test (DDT). The aim of the presented study was
      to evaluate the usefulness of the DDT in detecting central hearing disorders in
      school-age children. MATERIALS AND METHODS: During hearing screening programmes
      conducted in Poland in 2008-2010, exactly 235,664 children (7-12-years-old) were
      screened in 9,325 schools. Of this number, 7,642 were examined using the DDT test
      for CAPD. Screening programmes were conducted using the Sense Examination
      Platform. RESULTS: With the cut-off criterion set at the 5th percentile, results
      for the DDT applied in a divided attention mode were 11.4% positive for 7-year
      olds and 11.3% for 12-year-olds. In the focused attention mode, the comparable
      result for 12-year-olds was 9.7%. There was a clear right ear advantage. In
      children with positive DDT results, a higher incidence of other disorders, such
      as dyslexia, was observed. CONCLUSIONS: A test for CAPD should be included in the
      hearing screening of school-age children. The results of this study form the
      basis for developing Polish standards in this area.

PMID- 25780836
TI  - Detection of airborne allergen (Pla a 1) in relation to Platanus pollen in
      Cordoba, South Spain.
AB  - Cordoba is one of the Spanish cities with the highest records of plane tree
      pollen grains in the air. Clinical studies have identified Platanus as a major
      cause of pollinosis. This fact provokes an important public health problem during
      early spring when these trees bloom. The objective of the study is to evaluate
      the correlation between airborne pollen counts and Pla a 1 aeroallergen
      concentrations in Cordoba, to elucidate if airborne pollen can be an accurate
      measure that helps to explain the prevalence of allergenic symptoms. Pollen
      sampling was performed during 2011-2012 using a Hirst-type sampler. Daily average
      concentration of pollen grains (pollen grains/m 3 ) was obtained following the
      methodology proposed by the Spanish Aerobiology Network. A multi-vial cyclone was
      used for the aeroallergen quantification. Allergenic particles were measured by
      ELISA using specific antibodies Pla a 1. The trend of Platanus pollen was
      characterized by a marked seasonality, reaching high concentrations in a short
      period of time. Airborne pollen and aeroallergen follow similar trends. The
      overlapping profile between both variables during both years shows that pollen
      and Pla a 1 are significantly correlated. The highest significant correlation
      coefficients were obtained during 2011 and for the post peak. Although some
      studies have found notable divergence between pollen and allergen concentrations
      in the air, in the case of Platanus in Cordoba, similar aerobiological dynamics
      between pollen and Pla a 1 have been found. Allergenic activity was found only
      during the plane tree pollen season, showing a close relationship with daily
      pollen concentrations. The obtained pollen potency was similar for both years of
      study. The results suggest that the allergenic response in sensitive patients to
      plane tree pollen coincide with the presence and magnitude of airborne pollen. 

PMID- 25780837
TI  - Total hip arthroplasty in the treatment of degenerative disorders in rural and
      urban patients - A retrospective, randomised and controlled study.
AB  - INTRODUCTION: Farming is hard work which may lead to overstrain and
      osteoarthritis of the hip and knee. Hip osteoarthritis has been rarely discussed
      in the Polish literature. OBJECTIVE: The objective of the study was to determine
      the differences in hip osteoarthritis in urban and rural patients. The
      differences concern: prevalence, etiology, degree of degeneration and time spent
      in hospital. MATERIALS AND METHOD: Hospital records of 200 patients were analysed
      who were divided into 2 groups. Group A consisted of 79 rural patients: 39 males
      (49.4%) and 40 females (50.6%), mean age 66.09 (+/-9.48), mean BMI - 27.26 (+/
      4.47). Group B consisted of 121 urban patients: 51 males (42.1%), and 70 females
      (57.9%), mean age 67.74 (+/-8.88); mean BMI - 27.33 (+/-4.21). RESULTS: There
      were no differences observed regarding hospitalization times, but statistically
      significant differences were noted concerning the causes of osteoarthritis in
      both the rural and urban patients. No statistically significant differences were
      found between the types of prosthetic implants. CONCLUSIONS: 1) There are no
      differences between rural and urban patients who received surgical treatment for
      hip osteoarthritis, although more patients operated upon were urban patients. 2)
      The degree of hip degeneration was greater in rural patients.

PMID- 25780838
TI  - Do polyomavirus hominis strains BK and JC play a role in oral squamous cell
      carcinoma?
AB  - INTRODUCTION: Head and neck cancers are the most common cancers worldwide. It is
      estimated that approximately 90% of all head and neck cancers are represented by
      squamous cell carcinoma (SCC). There are many risk factors causing this type of
      cancer, including environmental factors and lifestyle choices, such as tobacco
      smoking or abusing alcohol. Other important risk factor include infectious
      factors. OBJECTIVE: The aim of this study was to analyze the prevalence of BK and
      JC virus infections among patients with oral squamous cell carcinoma (OSCC).
      MATERIALS AND METHOD: The correlation between BKV infection and OSCC, and
      correlation between BKV, OSCC, alcohol abuse, tobacco smoking, demographic data,
      pre-treatment staging, metastases of lymph node evidence, and grading, was
      analyzed. The study group consisted of 92 patients with squamous cell carcinoma
      (OSCC), 75 males, and 17 females, aged between 40 - 87 (average 56.8). All the
      patients underwent surgery and were not subjected to chemotherapy or radiotherapy
      prior to treatment. The analyzed samples were collected from paraffin sections.
      RESULTS: BKV DNA was detected in 18.5% of patients with OSCC. In the control
      group, BKV DNA was detected in 3.3%. BKV DNA was statistically more frequently
      detected among patients with squamous carcinoma, compared to the control group
      (p<0.05). CONCLUSIONS: The obtained results suggest that the BKV virus may play
      an important role in the development of oral squamous cell carcinoma.

PMID- 25780839
TI  - The detection of areas in Poland with an increased prevalence of isolated cleft
      lip with or without cleft palate.
AB  - INTRODUCTION AND OBJECTIVES: It is difficult to identify the environmental
      factors which together influence the occurrence of congenital malformations. It
      could be helpful to define the geographic location of the areas with an increased
      prevalence of such malformations. The aim of this study is to define if there are
      regions in Poland where the prevalence of isolated cleft lip, with or without a
      cleft palate (CL+/-P), is increased, and to present a method for searching for
      such areas. MATERIALS AND METHODS: The analysis included the whole area of Poland
      monitored in 2007-2008 by the Polish Register of Congenital Malformations (PRCM).
      The area was divided into 3,045 census regions. The number of children with CL+/
      P in those years was 514, and the size of the reference population (live births)
      was 802,372. Two methods were used for the detection of clusters with an
      increased prevalence of isolated CL+/-P: the LISA analysis and Kulldorff's scan
      statistic, and described in detail. RESULTS: The prevalence of isolated CL+/-P
      and the smoothed prevalence were calculated for every community. The results of
      the LISA and Kulldorff's analyses were consistent. Both methods located the sites
      with an increased prevalence of isolated CL+/-P. The lack of statistical
      significance of clusters indicated by Kulldorff's statistic, and the significance
      of clusters detected with the use of the LISA method, indicated the existence of
      clusters with an only slightly increased prevalence of isolated CL+/-P.
      CONCLUSIONS: The study shows the usefulness of the LISA and Kulldorff's spatial
      analyses in epidemiological studies, including the etiology of congenital
      malformations. Because the two methods work in different ways, good results can
      be obtained when they are used together.

PMID- 25780840
TI  - Association of socio-economic and demographic factors with physical activity of
      males and females aged 20-69 years.
AB  - OBJECTIVE: To assess the physical activity of working residents of Warsaw aged 20
      69 years, as well as to identify the socio-demographic factors associated with
      their levels of physical activity. MATERIALS AND METHOD: The study involved 2,544
      working residents of Warsaw aged 20-69 years. The short version of the IPAQ was
      applied and four physical activity levels (insufficient, sufficient, augmented,
      high) were distinguished. The relationships between physical activity and gender,
      age, BMI, education, economic and martial status as well as participation in
      recreation were determined. RESULTS: High levels of physical activity were
      reached by 8% of respondents, 22% achieved augmented level, 32% were sufficiently
      and 32% insufficiently active. Out of 2544 studied subjects, 6% declared complete
      sedentariness. Females were, as compared to males, more frequently (p<0.05)
      insufficiently active (35.9 vs. 31.9%). In obese and overweight subjects
      insufficient physical activity predominated (42.9 and 36.2%, respectively) and
      was significantly more frequent than in subjects with normal BMI (31.0%).
      Moreover, the subjects living in partner relationships were significantly
      (p<0.05) more frequently insufficiently active than those staying single (36.3
      vs. 30.3%). Respondents who declared regular participation in leisure activities
      were less frequently insufficiently active (20.0%) and more frequently met the
      criteria of sufficient (37.6%), augmented (28.0%) or high (14.4%) level of
      physical activity. No significant effects were found with respect to education of
      respondents. CONCLUSIONS: Prophylactic schedules associated with the improvement
      of physical activity level should be addressed particularly to females, people
      taking up recreation occasionally or to those not involved in recreation at all,
      living in partner relationships, youngest (21-30 years), in obese and overweight
      and in the lowest economic category.

PMID- 25780841
TI  - Gender and Age - Dependent effect of type 1 diabetes on obesity and altered body
      composition in young adults.
AB  - INTRODUCTION AND OBJECTIVE: The aim of the study was to evaluate the influence of
      age and gender on the prevalence of overweight and obesity, body composition and
      fatty tissue distribution in young adults with type 1 diabetes. MATERIAL AND
      METHODS: 197 patients with type 1 diabetes aged 20-40 years participated in the
      study. The control group consisted of 138 healthy adults. Body weight, height,
      waist and hip circumferences were measured. Analysis of body mass composition was
      performed using the bioimpedance. Study groups were stratified into cohorts aged
      <30 and 30+ years. RESULTS: Overweight and obesity were diagnosed in 35.5% and
      13.2% of diabetic patients and in 26.1% and 7.3% of the control group,
      respectively (p=0.016). In the whole study group, advanced age (OR=1.10; p<0.001)
      and diabetes mellitus (OR=2.25; p=0.001) predisposed patients to excess body
      weight. Women had a lower prevalence of overweight and obesity, but a trend
      toward excessive body mass was observed in diabetic females (OR=1.18; p=0.181).
      Diabetic females more often had abdominal obesity than control females (mean
      difference - 19.2%; p=0.020). Higher total body fat mass was found in the
      diabetic group (p=0.037). Diabetic females had a higher amount of absolute
      (p<0.001) and relative body fat mass (p=0.002), fat free mass (p=0.007), relative
      arm (p=0.007), leg (0<0.001) and trunk (p-=0.006) fat mass than control females.
      Diabetic males showed only higher relative fat mass of the lower limbs compared
      to control males (p=0.018). CONCLUSIONS: Patients with type 1 diabetes develop
      overweight and obesity in early adulthood more frequently than the general
      population and are characterized by higher body fat mass. Gender-related
      differences in body weight and composition in young type 1 diabetic adults were
      found.

PMID- 25780842
TI  - Prevalence of Internet addiction and risk of developing addiction as exemplified
      by a group of Polish adolescents from urban and rural areas.
AB  - OBJECTIVE: The objective of the study was to determine the prevalence of Internet
      addiction and the risk of developing this addiction in Polish adolescents
      attending junior high schools and high school in Lublin Province, to indicate the
      differences regarding the intensity of Internet addiction symptoms, and the types
      of online activity of adolescents residing in urban and rural areas. MATERIAL AND
      METHODS: The examined group comprised 1,860 participants (1,320 girls and 540
      boys) with an average age of 17 years. 760 students lived in urban areas and
      1,100 lived in rural areas. The following were used in the study: the Socio
      demographic Questionnaire designed by the authors, the Internet Addiction
      Questionnaire designed by Potembska, the Internet Addiction Test by Young and the
      Internet Addiction Questionnaire (Kwestionariusz do Badania Uzaleznienia od
      Internetu - KBUI) designed by Pawlowska and Potembska. RESULTS: The adolescents
      living in urban areas showed a significantly greater intensity of Internet and
      computer addiction symptoms measured by the KBUI Questionnaire, compared to those
      living in rural areas. CONCLUSIONS: The Internet addiction criteria were
      fulfilled by 0.45% of adolescents living in urban areas and 2.9% of those living
      in rural areas, whereas 35.55% of urban dwelling students and 30.18% of students
      living in rural areas showed a risk of developing this addiction. More
      adolescents living in urban areas, compared to those living in rural areas, use
      Internet pornography, play computer games, disclose their personal data to
      unknown individuals encountered on the Internet, use Instant Messaging (IM)
      services, electronic mail and Facebook social networking service. Compared to
      their peers from urban areas, significantly more adolescents from rural areas use
      'Nasza Klasa' (Our Classmates) online social networking service.

PMID- 25780843
TI  - Occupational accidents with mowing machines in Austrian agriculture.
AB  - The number of recognized accidents during agricultural work is still very high in
      Austria. In the years 2008 to 2009, there occurred 84 approved work accidents
      with mowing machines. The main causes of accidents were the loss of control of
      machines, transportations or conveyances, hand tools, objects or animals. In the
      literature, numerous studies of general agricultural and forestry accident
      situations are available. Detailed studies on specific types of agricultural
      machines, which describe concrete circumstances and causes of accidents, are in
      limited numbers. The accident database from the General Accident Insurance
      Institution and the Austrian Social Insurance Institution of Farmers, with
      personal and accidental data information about mowing machine accidents, were
      analyzed. The results showed that most accidents occurred on mixed agricultural
      farms (68%). The majority of the injured persons were male (86%), over 40-years
      old (86%) with an agricultural or forestry education (91%). The most common
      accidents occurred in the summer months (69%) and on afternoons during the
      working week (79%). The majority of accidents were caused by contact with the
      machine (55%) and the loss of control (73%) during their operation (60%) and
      harvesting work (63%). The most frequently injuries were wounds, fractures and
      superficial injuries (81%) to the upper and lower extremities (66%). The results
      of the chi-square test showed significant correlations between the specific task
      with the form of contact, the working process, the day and season. Results of the
      odds ratio determination showed an increased risk of suffering serious injury for
      men in the first half of the year and half of the day due to loss of control over
      the machine during agricultural harvesting work. 

PMID- 25780844
TI  - Evaluation of influence of stretching therapy and ergonomic factors on postural
      control in patients with chronic non-specific low back pain.
AB  - INTRODUCTION AND OBJECTIVES: The vertical orientation of the body in the upright
      standing position is maintained by keeping the body's centre of gravity (COG)
      upright, above the base of support, by a dynamic interplay of visual, vestibular,
      and somatosensory control systems. The objectives of this study were: to compare
      the postural control strategy between people with and without low back pain
      (LBP), to estimate the influence of the stretching therapy on the postural
      control strategy, and to discover the relationship between the restriction of
      spine mobility and occurrence of some ergonomic factors. MATERIALS AND METHODS:
      The study consisted of 32 patients with LBP and 25 healthy controls. Postural
      characteristics of the subjects were measured with the use of a computerized
      force platform. The software programme filters and measures COG sway velocity in
      different conditions. Additional measurements and tests were conducted in
      patients after stretching therapy. Based on survey research, all individuals were
      selected and evaluated from the aspect of ergonomics. RESULTS: The results of the
      COG sway velocity vary under the testing conditions. From the aspect of ergonomic
      attitude and influence of the rehabilitation, results varied in the groups.
      CONCLUSIONS: Ergonomic factors are often accompanied by the appearance of LBP.
      The restrictions within the musculoskeletal system cause disorders in muscle
      synergies, which is expressed by an increase in the angular velocity of the COG.
      In patients with chronic back pain syndrome, selected stretching therapy
      techniques improves the range of motion of the spine and reduces pain.

PMID- 25780845
TI  - An evaluation of life satisfaction and health - Quality of life of senior
      citizens.
AB  - INTRODUCTION AND OBJECTIVE: Modern medicine is still searching for the
      antecedents which will lead to successful aging. The article discusses the self
      perception of life satisfaction and health of senior citizens. The aim of the
      study was to determine the relationship between self-evaluation of life
      satisfaction and health by senior citizens in comparison to different age groups.
      MATERIALS AND METHOD: The study included 463 persons - 230 men and 233 women. The
      age of the participants was in the range 16 - 83 years. All participants were
      asked to fill the Life Satisfaction Questionnaire (Fragebogen zur
      Lebenszufriedenheit - FLZ). The FLZ questionnaire assesses the global life
      satisfaction of a person and health domain separately. RESULTS: The results show
      age-related differences in the evaluation of life satisfaction. Accordingly,
      there is a significant change in health evaluations in different age groups, but
      there are no significant gender differences in health self-report data. The
      senior citizens' assessment of general health, although the lowest among all the
      age-subgroups, showed significant difference only in relation to the people below
      45 years of age. The significant differences in satisfaction from mental health
      occurred only for the elderly and participants aged 25-34 and 35-44. CONCLUSIONS:
      Life satisfaction is associated with subjective health evaluations. There are two
      domains (mental health and performance) that are positively evaluated by more
      than two-thirds of senior citizens. The observed differences challenge
      stereotypes and prejudices relating to negative aging process. Senior citizens
      can improve their control beliefs and develop self-regulation and coping skills.

PMID- 25780846
TI  - Symptoms of depression among adults in rural areas of western Poland.
AB  - OBJECTIVE: To measure the intensity of depressive symptoms in the populations
      residing in rural areas of western Poland, and to delineate the putative
      association between the intensity of depression and selected socio-demographic
      and clinical factors. MATERIALS AND METHOD: The study covered 445 adults
      recruited from one family physician practice in the rural area of Wielkopolska
      region. The following tools were applied: Beck Depression Inventory (BDI), the
      WHO WHOQoL-Bref quality of life assessment scale, and a socio-demographic and
      clinical questionnaire elaborated by the authors. RESULTS: Depressive symptoms
      were observed in approx. 30% of the patients. The intensity of symptoms
      correlated with age, female gender, and inversely correlated with the quality of
      life. There was no association between depressive symptoms and level of education
      (counted as years of education), number of somatic illnesses, and family burden
      of psychiatric disorders. CONCLUSION: Symptoms of depression were noted in
      approx. 30% of patients who consulted their family physician. The Beck
      questionnaire is a simple tool whose application could decidedly improve the
      recognition of depression. It is worth taking note of factors that may be
      connected with the intensity of depressive symptoms - gender, the number of
      diagnosed somatic illnesses, and the quantity of drugs administered.

PMID- 25780847
TI  - Patient rights, risk, and responsibilities in the genetic era - a right to know,
      a right not to know, or a duty to know?
AB  - INTRODUCTION AND OBJECTIVE: As genetics tests ordered by physicians have
      implications not only for patients but also their relatives, they create a
      bioethical dilemma for both clinicians and patients. Especially when a patient is
      reluctant to undergo the test, know the genetic risk, and share such information
      with others. While international biomedical law recognises the right not to know
      one's genetic status, it has been criticised for many reasons. This paper
      outlines the arguments for and against the right not to know about genetic risk.
      Abbreviated description of the state of knowledge. Both medicine and bioethics
      acknowledge that information about genetic risk affects not only the individual
      but also other family members. Consequently, many argue that such information is
      not a private matter and should be regarded not as a right but as an obligation,
      or even a duty. Thus, it is emphasized that one's right not to know is strictly
      related to the duty to inform others about any genetic risk. Yet others believe
      that constant proliferation of genetic testing and moralization of health issues
      poses a serious threat to patient rights and creates new opportunities for social
      surveillance and control. In both cases there can be observed an increasing
      'bioethecization' of genetic discourse. SUMMARY: The paper suggests that the
      developments in genetics result in the emergence of new molecular ethics which
      stress that individuals have a moral and political duty to undergo the test, know
      the risk, and disclose that information to others. Consequently, it may transform
      the right to know into a duty and poses the question whether in the genetic
      context individuals should have the right to remain ignorant. Finally, the paper
      argues that genetic literacy becomes a source of biological citizenship.

PMID- 25780848
TI  - Long-term risk of complications after mid-urethral sling IVS implantation.
AB  - INTRODUCTION: Results of short-term evaluation of multifilament microporous
      midurethral tape IVS differ a great deal. During the first year of implantation,
      erosions have been observed in 0%-26% of operated women. Long-term observations
      are rare. They suggest high risk of extrusion and infection even after years of
      implantation. OBJECTIVE: The purpose of the study was to evaluate long-term risk
      of complications after IVS implantation. MATERIAL AND METHODS: Between 2001-2005,
      72 women were operated on with the use of IVS mid-urethral tape. RESULTS: Two
      women had vaginal erosions during the first 3 months after the operation. Twelve
      women had vaginal erosions, purulent vaginal discharge, with IVS tape sticking
      out of the abdominal wall or vagina, and abdominal abscess. These complications
      were diagnosed between 9 months and 6 years after IVS implantation. The patients
      were operated on vaginally and open abdominally, 1-5 times because of
      complications after IVS implantation. CONCLUSIONS: In the case of post-IVS
      complication, as much tape as possible should be excised. Long-term follow up on
      patients with IVS implantation should be recommended to the centres where IVS
      tape was used, even to patients after removal of the tape. Risk of erosion,
      extrusion and infection after midurethral multifilament microporous IVS tape
      implantation is too high - which is the reason it should no longer be used.

PMID- 25780849
TI  - Effect of transdermal hormone therapy on platelet haemostasis in menopausal
      women.
AB  - INTRODUCTION: Despite the undeniably positive effect on the quality of life of
      menopausal women, menopausal hormone therapy (HT) also has negative side-effects,
      which include, among others, thromboembolic complications. OBJECTIVE: To assess
      the effect of a popular type of this therapy - transdermal HT on platelet
      hemostasis, which plays a significant role in intravascular coagulation.
      MATERIALS AND METHOD: The study group consisted of 92 postmenopausal women: 1)
      group G1 (n=30), treated with transdermal HT (17beta-estradiol 50 MUg/day plus
      NETA 170 MUg/day); 2) group G2 (n=31), treated with the above transdermal HT and
      low dosage of acetylsalicylic acid (ASA); 3) control group P (n=31). All the
      women qualified for the study had two or more risk factors for arterial
      thrombosis, such as: smoking, hypertension, visceral obesity,
      hypercholesterolaemia, hypertriglyceridaemia, elevated levels of PAI-1, and
      increased fibrinogen, increased activity of coagulation factor VII. RESULTS:
      After three months of therapy, in the G1 group there was a decrease in platelet
      count (p = 0.004) and a decrease in GP IIb/IIIa - a platelet receptor for
      fibrinogen (p = 0.022). In the G2 group, no changes in the tested parameters were
      observed. CONCLUSIONS: 1) Transdermal HT in the form of combined, estrogen
      progestogen patches favourably modifies platelets haemostasis, reversing the
      adverse effects that occur after menopause. 2) The use of low ASA doses as a
      thromboprophylaxis in short-term transdermal HT is not necessary.

PMID- 25780850
TI  - Release of bisphenol A and its derivatives from orthodontic adhesive systems
      available on the European market as a potential health risk factor.
AB  - INTRODUCTION: Treatment with fixed orthodontic appliances requires the
      application of adhesive systems to enable secure fastening of brackets and
      retainers to the surface of tooth enamel. The orthodontic bonding systems are
      similar in terms of chemical composition to dental filling materials, the
      chemical stability of which is not satisfactory. Particularly alarming is the
      release of bisphenol A and its derivatives to the external environment, which has
      been well-documented for materials used in conservative dentistry. OBJECTIVES:
      The aim of the study was an in vitro assessment of the release of biologically
      harmful bisphenol A and its derivatives from orthodontic adhesives available on
      the European market, as a potential health risk factor for orthodontic patients.
      MATERIAL AND METHODS: The study assessed levels of BPA, BPA polymers and Bis-GMA
      resin in eluates of six commonly used orthodontic adhesives: Light Bond,
      Transbond XT, Resilence, Aspire, GrenGloo and ConTec LC, obtained after one hour,
      24 hours, 7 days and 31 days of material sample storage in water. The presence
      and concentration of the studied chemicals in the obtained solutions were
      identified using the HPLC method. RESULTS: The highest (p<=0.05) concentration of
      BPA at 32.10ug/ml was observed in the Resilence material eluates. The highest
      concentration of poly-bisphenol A was found in solutions obtained after
      incubation of ConTec LC adhesive at 371.90ug/ml, whereas the highest amount of
      Bis-GMA resin (425.07ug/ml) was present in Aspire material eluates. CONCLUSIONS:
      1) In conditions of the current experiment it was demonstrated that most of the
      assessed orthodontic adhesive resins available on the European market and
      released into the outside environment - biologically harmful bisphenol A or its
      derivatives, posing a potential threat to the patients' health. 2) Release of BPA
      and its derivatives into aqueous solutions is the highest in the early stages of
      sample incubation.

PMID- 25780851
TI  - Are cognitive functions in post-menopausal women related with the contents of
      macro- and micro-components in the diet?
AB  - The objective of the study was an evaluation of the relationship between the
      level of cognitive functions and contents of micro- and macro-components in the
      diet of postmenopausal women. A group of 402 women was recruited to the study.
      The inclusion criteria were: minimum two years after the last menstruation, FSH
      concentration 30 U/ml and no dementia signs on the Montreal Cognitive Assessment
      (MoCA). A computerized battery of the Central Nervous System Vital Signs (CNS VS)
      test was used to diagnose cognitive functions. The dietary questionnaire was
      evaluated based on observation of a seven-day diet. The data obtained were
      introduced into the database and analyzed using computer software DIETICIAN.
      Statistical analysis was performed using statistical software STATISTICA.
      RESULTS: The results of the study concerning diet unequivocally indicate a very
      poor quality of diet in the group of postmenopausal women examined. The daily
      diet had a too high energetic value. The women consumed an excessive amount of
      total fat, including definitely too much monounsaturated fatty acids, and
      insufficient polyunsaturated fatty acids. The dietary intake of sodium and
      phosphorus was too high, whereas deficiencies were observed in the consumption of
      iron, copper, potassium, calcium, magnesium and zinc. No significant correlations
      were found in the analysis of cognitive functions according to the energetic
      value of daily diet and contents of macro- and micro-components. The results
      concerning verbal memory significantly depended on the daily intake of
      polyunsaturated fatty acids. Women who consumed polyunsaturated fatty acids below
      the daily normal or normal level obtained significantly higher results in verbal
      memory.

PMID- 25780852
TI  - Evaluation of symptoms of anxiety and depression in women with breast cancer
      after breast amputation or conservation treated with adjuvant chemotherapy.
AB  - OBJECTIVE: Evaluation of the presence of symptoms of anxiety and depression in
      women treated for breast cancer who underwent surgical procedure using one of two
      alternative methods, either radical mastectomy or breast conserving treatment
      (BCT). METHODS: A questionnaire survey involved 85 patients treated in a
      conservative way and 94 patients after breast amputation. Hospital Anxiety and
      Depression Scale (HADS), Beck Depression Inventory (BDI) and depression degree
      evaluation questionnaire were used in the study. The patients' esponses were
      statistically analyzed. RESULTS: Based on the HADS questionnaire, the total
      anxiety level in the group of women treated with BCT was 6.96 points, while in
      the group of patients who had undergone mastectomy the value was 7.8 points. The
      observed results were statistically significant. In the case of depression, the
      following values were found: patients after amputation had 8.04 scale value
      points, and those after BCT had 6.8 scale value points. The observed differences
      were statistically significant. Negative correlation was found between the level
      of anxiety and depression. The total level of depression evaluated using the Beck
      scale was 16.3 points in the BCT group, which means that they suffered from mild
      depression, while in the mastectomy group the level was 19.6 points, which
      corresponds to moderate depression. CONCLUSIONS: The level of anxiety and
      depression among women with breast cancer was influenced by the type of the
      applied surgical procedure and adjuvant chemotherapy. Demographic variables did
      not influence the level of anxiety and depression.

PMID- 25780853
TI  - Regulatory focus moderates the social performance of individuals who conceal a
      stigmatized identity.
AB  - People often choose to hide a stigmatized identity to avoid bias. However, hiding
      stigma can disrupt social interactions. We considered whether regulatory focus
      qualifies the social effects of hiding stigma by examining interactions in which
      stigmatized participants concealed a devalued identity from non-stigmatized
      partners. In the Prevention Focus condition, stigmatized participants were
      instructed to prevent a negative impression by concealing the identity; in the
      Promotion Focus condition, they were instructed to promote a positive impression
      by concealing the identity; in the Control condition, they were simply asked to
      conceal the identity. Both non-stigmatized partners and independent raters rated
      the interactions more positively in the Promotion Focus condition. Thus,
      promotion focus is interpersonally beneficial for individuals who conceal a
      devalued identity. 

PMID- 25780854
TI  - Genetic analysis of river, swamp and hybrid buffaloes of north-east India throw
      new light on phylogeography of water buffalo (Bubalus bubalis).
AB  - This study analysed buffaloes from north-east India and compared their nuclear
      and mitochondrial DNA variations with buffaloes of mainland India, China,
      Mediterranean and South-East Asia. Microsatellite genotypes of 338 buffaloes
      including 210 from six north-east Indian buffalo populations and three mainland
      Indian breeds were analysed to evaluate their genetic structure and evolutionary
      relationships. Phylogenetic analysis and multidimensional scaling plot of
      pairwise FST revealed the clustering of all swamp-type buffaloes of north-east
      India with Lower Assamese (significantly hybrid type) buffaloes in one plane and
      all the mainland river buffaloes in another plane while the upper Assamese
      buffaloes being distinct from both these clusters. Analysis of mtDNA D-loop
      region of 530-bp length was performed on 345 sequences belonging to 23 buffalo
      populations from various geographical regions to establish the phylogeography of
      Indian water buffalo. The swamp buffaloes of north-east India clustered with both
      the lineages of Chinese swamp buffalo. Multidimensional scaling display of
      pairwise FST derived from mitochondrial DNA data showed clustering of upper
      Assamese, Chilika and Mediterranean buffaloes distinctly from all the other
      Indian buffalo populations. Median-joining network analysis further confirmed the
      distinctness and ancestral nature of these buffaloes. The study revealed north
      east region of India forming part of the wider hybrid zone of water buffalo that
      may probably extend from north-east India to South-East Asia. 

PMID- 25780856
TI  - Failure of empirical systemic antifungal therapy in mechanically ventilated
      critically ill patients.
AB  - RATIONALE: Systemic antifungal treatments are empirically administered to the
      sickest critically ill patients, often without documented invasive fungal
      infection. OBJECTIVES: To estimate the impact of systemic antifungal treatment on
      30-day survival of patients suspected to have invasive candidiasis. METHODS: All
      nonneutropenic, nontransplant recipients managed in five intensive care units
      intubated for at least 5 days, and free of invasive candidiasis, were included.
      To account for differences in patients' characteristics recorded daily before
      study end point, a causal model for longitudinal data was used to assess benefits
      from antifungal treatment. The composite primary end point was hospital mortality
      or occurrence of invasive candidiasis. MEASUREMENTS AND MAIN RESULTS: Among 1,491
      patients, 100 (6.7%) received antifungal treatment for a suspected infection.
      Patients treated with antifungals were more severely ill than untreated patients.
      Within the 30-day follow-up period, 363 (24.3%) patients died, and 22 (1.5%)
      exhibited documented invasive candidiasis. After adjustment on baseline and time
      dependent confounders (underlying illness, severity, invasive procedures, Candida
      colonization), and using a marginal structural model for longitudinal data,
      treatment was not associated with a decreased risk of mortality or of occurrence
      of invasive candidiasis (hazard ratio, 1.05; 95% confidence interval, 0.56-1.96;
      P = 0.91). CONCLUSIONS: This study failed to show outcome benefits for empirical
      systemic antifungal therapy in the sickest critically ill, nonneutropenic,
      nontransplanted patients. The post hoc power did not allow us to conclude to an
      absence of treatment effect especially for specific subgroups. Studies to refine
      indications for empirical treatment based on surrogate markers of invasive
      candidiasis are warranted.

PMID- 25780855
TI  - Proteomic profiling of the retinas in a neonatal rat model of oxygen-induced
      retinopathy with a reproducible ion-current-based MS1 approach.
AB  - Investigation of the retina proteome during hypoxia-induced retinal
      neovascularization is valuable for understanding pathogenesis of retinopathy of
      prematurity (ROP). Here we employed a reproducible ion-current-based MS1
      quantification approach (ICB) to explore the retinal proteomic changes in early
      stage of ROP in a rat model of oxygen-induced retinopathy (OIR). Retina proteins,
      which are rich in membrane proteins, were efficiently extracted by a detergent
      cocktail and subjected to precipitation/on-pellet-digestion, followed by nano-LC
      MS analysis on a 75-cm column with a 7-h gradient. The high reproducibility of
      sample preparation and chromatography separation enabled excellent peak alignment
      and contributed to the superior performance of ICB over parallel label-free
      approaches. In this study, sum-of-intensity with rejection was incorporated to
      determine the protein ratios. In total, 1325 unique protein groups were
      quantified from rat retinas (n = 4/group) with at least two distinct peptides at
      a protein FDR of 1%. Thirty-two significantly altered proteins were observed with
      confidence, and the elevated glial fibrillary acidic protein and decreased
      crystalline proteins in OIR retinas agree well with previous studies. Selected
      key alterations were further validated by Western blot analysis. Interestingly,
      Rab21/RhoA/ROCK2/moesin signaling pathway was found to be involved in retinal
      neovascularization of OIR. Moreover, highly elevated annexin A3, a potential
      angiogenic mediator, was observed in OIR retinas and may serve as a potential
      therapeutic target. In conclusion, reproducible ICB profiling enabled reliable
      discovery of many altered mediators and pathways in OIR retinas, thereby
      providing new insights into molecular mechanisms involved in pathogenesis of ROP.

PMID- 25780858
TI  - Exploring the limitations of age-based models for health care planning.
AB  - Health care decision makers are required to make planning decisions over a medium
      to long term planning horizon. Whilst population ageing is an important
      consideration for planners, age-stratified demographic models may produce
      misleading estimates of future resource requirements if the actual relationship
      between age and health is not fixed. We present a methodology which tests whether
      the assumption of a fixed age-health relationship is valid and estimate the
      magnitude of planning errors using a long time-series of measures of chronic
      health and service utilisation (N = 2419) taken from the Great British General
      Household Survey (1980-2008). We find that age-only models contain significant
      omitted variable bias, and that the relationship between age and health varies
      significantly across birth cohorts. Chronic sickness has fallen across birth
      cohorts born between 1890 and 2008, particularly before birth year 1930.
      Generational health improvements have mitigated the effects of population ageing,
      meaning that the population rate of sickness fell between 1980 and 2008. Planning
      based only on age leads to overestimation of the population level of health care
      need if successive cohorts are becoming healthier. Many alternative approaches
      exist which allow planners to relax the assumption of a fixed relationship
      between age and health. 

PMID- 25780857
TI  - Evaluation of von Willebrand factor phenotypes and genotypes in Hemophilia A
      patients with and without identified F8 mutations.
AB  - BACKGROUND: Hemophilia A (HA) is an X-linked bleeding disorder caused by a
      deficiency in factor VIII (FVIII). von Willebrand disease (VWD) is characterized
      by a quantitative or qualitative defect in von Willebrand factor (VWF). Patients
      with VWD with severely low VWF or VWD Type 2N (VWD2N), a VWD subtype
      distinguished by defective VWF binding to FVIII, may have reduced FVIII levels
      secondary to their VWD. These patients superficially resemble patients with HA
      and pose a potential for misdiagnosis. OBJECTIVES: To investigate the unexplained
      cause of bleeding in HA patients without known FVIII mutations by assessing
      plasma VWF antigen (VWF:Ag), FVIII binding capacities and VWF genotypes.
      PATIENTS/METHODS: Thirty-seven of 1027 patients with HA studied as part of the
      Hemophilia Inhibitor Research Study lacked identifiable F8 mutations. These
      patients (cases) and 73 patients with identified F8 mutations (controls) were
      evaluated for VWF:Ag, a patient's VWF capacity to bind FVIII (VWF:FVIIIB) and VWF
      sequence. RESULTS: Four cases had VWF:Ag < 3 IU dL(-1) and VWF mutations
      consistent with Type 3 VWD. Six cases and one control were heterozygous for
      mutations previously reported to cause Type 1 VWD (VWD1) (n = five cases and one
      control) or predicted to be deleterious by Polyphen2 and SIFT prediction tools (n
      = 1 case). One control had VWF:Ag < 30 IU dL(-1) and seven patients (four cases
      and three controls), including two cases who were heterozygous for a known VWD2N
      mutation, had reduced VWF:FVIIIB. CONCLUSIONS: These data emphasize that some
      patients diagnosed with HA require VWF assessments in order to achieve a
      comprehensive diagnosis and an optimal treatment strategy.

PMID- 25780859
TI  - Relationship between Dongting Lake and surrounding rivers under the operation of
      the Three Gorges Reservoir, China.
AB  - The natural flow properties of the Yangtze River have been changed completely
      following the construction of the Three Gorges Dam. The dam's operation has
      affected the resources and environment in the middle and lower reaches of the
      Yangtze River, changing the hydrological conditions and ecological environment of
      the Dongting Lake. During three different dispatching periods of the reservoir,
      we took triplicate samples of the river and lake water. All the samples were
      analysed for delta(2)H and delta(18)O to determine the relationship between the
      lake and the Yangtze River (and other rivers), and to evaluate objectively the
      influence of the dam's operation on the lake. During the period of water-supply
      dispatch, the Four Rivers and Miluo River are the main recharge sources of the
      lake. During the flood-storage dispatching period, the Dongting Lake is recharged
      largely by the Three Outlets and the Four Rivers, whereas during the period of
      water-storage dispatch, most of the lake's water originates from the Miluo,
      Xiang, Zi, and Yuan rivers. Although the Yangtze River only contributes
      significantly to the lake's recharge through the Three Outlets during the flood
      storage dispatching period, the lake discharges large amounts of water into the
      Yangtze River during all three periods. Through the operation of the reservoir,
      it should be ensured that the water level of the Dongting Lake is not too low
      during the dry season, nor too high during the wet season, thus preventing the
      lake region from future flood and drought disasters. 

PMID- 25780860
TI  - Phospholipid bilayer-coated aluminum nanoparticles as an effective vaccine
      adjuvant-delivery system.
AB  - The phospholipid bilayer-coated aluminum nanoparticles (PLANs), formed via
      chemisorption, were prepared by reverse ethanol injection-lyophilization (REIL)
      utilizing the phosphophilicity of aluminum. The anhydrous antigen-loaded PLANs
      obtained by REIL proved stable, satisfying using the controlled-temperature-chain
      instead of the integrated cold-chain for distribution, and could be rehydrated to
      reconstitute instantly an aqueous suspension of the antigen-PLANs, which were
      more readily taken up by antigen-presenting cells and, when given subcutaneously
      to mice, induced more robust antigen-specific humoral and cellular
      immunoresponses but less local inflammation than the antigen-alum. Thus, the
      PLANs are a useful vaccine adjuvant-delivery system with advantages over the
      widely used naked alum. 

PMID- 25780861
TI  - The 'hero syndrome': a human condition of the ICU?

PMID- 25780862
TI  - A Bayesian network for assessing the collision induced risk of an oil accident in
      the Gulf of Finland.
AB  - The growth of maritime oil transportation in the Gulf of Finland (GoF), North
      Eastern Baltic Sea, increases environmental risks by increasing the probability
      of oil accidents. By integrating the work of a multidisciplinary research team
      and information from several sources, we have developed a probabilistic risk
      assessment application that considers the likely future development of maritime
      traffic and oil transportation in the area and the resulting risk of
      environmental pollution. This metamodel is used to compare the effects of two
      preventative management actions on the tanker collision probabilities and the
      consequent risk. The resulting risk is evaluated from four different
      perspectives. Bayesian networks enable large amounts of information about
      causalities to be integrated and utilized in probabilistic inference. Compared
      with the baseline period of 2007-2008, the worst-case scenario is that the risk
      level increases 4-fold by the year 2015. The management measures are evaluated
      and found to decrease the risk by 4-13%, but the utility gained by their joint
      implementation would be less than the sum of their independent effects. In
      addition to the results concerning the varying risk levels, the application
      provides interesting information about the relationships between the different
      elements of the system. 

PMID- 25780865
TI  - Reduced sensitivity of the renal vasculature to angiotensin II in young rats: the
      role of the angiotensin type 2 receptor.

PMID- 25780866
TI  - Mast cells mediate hyperoxia-induced airway hyperreactivity in newborn rats.

PMID- 25780867
TI  - Neuroprotective effects of pregabalin in a rat model of intracisternal facial
      nerve avulsion.
AB  - BACKGROUND: Pregabalin (PGB), a drug used for treating neuropathic pain, has
      immune-modulating property that may have therapeutic implications. Suppression of
      microglial activation and improvement in functional recovery was observed in
      experimental spinal cord injury after PGB administration. An experimental study
      was conducted to evaluate whether PGB could afford neuroprotection in a rat model
      of intracisternal facial nerve avulsion. METHODS: Twenty-eight male Wistar rats
      (250-300 g) were dichotomized into two groups: a PGB group (N.=14) and a control
      group (N.=14). The PGB group received a total of 4 intraperitoneal PGB injections
      (30 mg/kg, 15 minutes preoperatively and 4, 24, and 48 hours postoperatively),
      and the control group underwent intraperitoneal saline injection. Intracisternal
      facial nerve avulsion was created by tangential pull-out of the nerve surgically
      exposed at the stylomastoid foramen. In both groups, the brainstem containing the
      facial motor nuclei neurons was thin-sliced and stained with cresyl violet, and
      the number of viable neurons in the facial motor nuclei on days 14 and 28 was
      counted under microscope. RESULTS: The total viable neuron count was
      significantly greater in the PGB group than in the Control group both on day 14
      (271.4+/-14.9 vs. 196.2+/-22.2, P<0.01) and day 28 (160.2+/-21.6 vs. 102.6+/
      13.4, P<0.01). Furthermore, CD11b/c immunostaining on days 3 and 8 showed that
      CD11b/c-positive cells, suggestive of activated microglia, were observed only in
      the control group. CONCLUSIONS: Better neuronal survival by PGB administration
      may be beneficial and clinically relevant when surgical reconstruction of the
      facial nerve, such as hypoglossal-facial nerve anastomosis, is considered.

PMID- 25780868
TI  - Risk factors for falls and cognitive decline in older individuals.

PMID- 25780869
TI  - Geriatric patients with cognitive impairment.
AB  - BACKGROUND: Hospitals are now faced with increasing numbers of cognitively
      impaired patients aged 80 and older who are at increased risk of treatment
      complications. This study concerns the outcomes when such patients are treated in
      a specialized ward for cognitive geriatric medicine. METHODS: Observation of a
      cohort of 2084 patients from 2009 to 2014, supplemented by a sample of 380
      patients from the hospital cohort of the Longitudinal Urban Cohort Ageing Study
      (LUCAS) for the years 2010 and 2011. RESULTS: Geriatric inpatients with cognitive
      impairment tend to be multimorbid. Half of the patients studied (1031 of 2084
      patients) were admitted to the hospital on an emergency basis. Complications
      arising on the ward that necessitated transfer elsewhere arose in 2.6% (51 of
      2084 patients). Moreover, analysis of the sample of 380 patients from the LUCAS
      cohort revealed that the treatments they underwent during hospitalization were
      associated with an improvement of their functional state: their mean overall
      score on the Barthel index rose from 39.8 +/- 24.3 (median, 35) on admission to
      52.7 +/- 27.0 (median, 55) on discharge. The percentage of patients being treated
      with 5 or more drugs fell from 98.2% (373/380) on admission to 79.3% (314/362) on
      discharge. The percentage receiving potentially inappropriate medications (PIM),
      as defined by the PRISCUS list, fell from 45% to 13.3%, while the percentage of
      drug orders and prescriptions involving PIM fell from 7.8 % (327/4181) to 2.0%
      (53/2600). 70% of the patients were discharged to the same living situation where
      they had been before admission. CONCLUSION: In this study, structured geriatric
      treatment in a cohort of older acutely ill patients with cognitive impairment was
      associated with improvement of functions that are relevant to everyday life, as
      well as with a reduction of polypharmacy. Controlled studies are needed to
      confirm the observed benefit.

PMID- 25780870
TI  - Treatment in a center for geriatric traumatology.
AB  - BACKGROUND: Although the number of elderly patients with fractures is increasing,
      there have been only a few studies to date of the efficacy of collaborative
      treatment by trauma surgeons and geriatricians. METHODS: Data on patients over
      age 75 with femoral neck, trochanteric, proximal humeral, and pelvic ring
      fractures were evaluated from the eras before and after the establishment of a
      certified center for geriatric traumatology (CGT) (retrospective analysis, n =
      169; prospective analysis, n = 216). Moreover, data were also analyzed from
      younger patients (aged 65-74) with the same types of fracture who were not
      treated in the CGT. The main outcome parameter was in-hospital mortality. Other
      ones were the frequency and length of stays in the intensive care unit, the
      overall length of hospital stay, and the use of inpatient rehabilitation after
      acute hospitalization. RESULTS: Before the CGT was established, 20.7% of all
      patients over age 75 (95% confidence interval [CI], 14.8-27%) were treated in an
      intensive care unit; the corresponding figure after the establishment of the CGT
      was 13.4% (95% CI, 9.3-18.5%, p = 0.057). The mean length of stay in the
      intensive care unit before and after establishment of the CGT was 48 hours (95%
      CI, 32-64 hours) and 53 hours (95% CI, 29-77 hours), respectively (p = 0.973).
      The in-hospital mortality declined from 9.5% (95% CI, 5.3-13.8%) to 6.5% (95% CI,
      3.7-9.5%, p = 0.278), while the overall length of hospital stay increased from
      13.7 days (95% CI, 12.6-14.8 days) to 16.9 days (95% CI, 16.1-17.7 days,
      p<0.001). The percentage of patients transferred to an inpatient rehabilitation
      facility upon discharge decreased slightly, from 53.8% to 49.1%. Among the
      younger patients who were not treated in the CGT, no comparable trends were seen
      toward lower in-hospital mortality or toward less treatment in an intensive care
      unit. In fact, the developments over time in the younger age group tended to be
      in the opposite direction.0.001). The percentage of patients transferred to an
      inpatient rehabilitation facility upon discharge decreased slightly, from 53.8%
      to 49.1%. Among the younger patients who were not treated in the CGT, no
      comparable trends were seen toward lower in-hospital mortality or toward less
      treatment in an intensive care unit. In fact, the developments over time in the
      younger age group tended to be in the opposite direction. CONCLUSION: The
      collaborative treatment of elderly patients with fractures by trauma surgeons and
      geriatric physicians can markedly improve their acute care.

PMID- 25780871
TI  - Better risk assessment for individual substances.

PMID- 25780872
TI  - In reply.

PMID- 25780873
TI  - Intrinsic and Extrinsic Contributions to Seated Balance in the Sagittal and
      Coronal Planes: Implications for Trunk Control After Spinal Cord Injury.
AB  - The contributions of intrinsic (passive) and extrinsic (active) properties of the
      human trunk, in terms of the simultaneous actions about the hip and spinal
      joints, to the control of sagittal and coronal seated balance were examined. Able
      bodied (ABD) and spinal-cord-injured (SCI) volunteers sat on a moving platform
      which underwent small amplitude perturbations in the anterior-posterior (AP) and
      medial-lateral (ML) directions while changes to trunk orientation were measured.
      A linear parametric model that related platform movement to trunk angle was fit
      to the experimental data by identifying model parameters in the time domain. The
      results showed that spinal cord injury leads to a systematic reduction in the
      extrinsic characteristics, while most of the intrinsic characteristics were
      rarely affected. In both SCI and ABD individuals, passive characteristics alone
      were not enough to maintain seated balance. Passive stiffness in the ML direction
      was almost 3 times that in the AP direction, making more extrinsic mechanisms
      necessary for balance in the latter direction. Proportional and derivative terms
      of the extrinsic model made the largest contribution to the overall output from
      the active system, implying that a simple proportional plus derivative (PD)
      controller structure will suffice for restoring seated balance after spinal cord
      injury. 

PMID- 25780875
TI  - Neuroimaging effects of prenatal alcohol exposure on the developing human brain:
      a magnetic resonance imaging review.
AB  - OBJECTIVE: This paper reviews the magnetic resonance imaging (MRI) literature on
      the effects of prenatal alcohol exposure on the developing human brain. METHOD: A
      literature search was conducted through the following databases: PubMed, PsycINFO
      and Google Scholar. Combinations of the following search terms and keywords were
      used to identify relevant studies: 'alcohol', 'fetal alcohol spectrum disorders',
      'fetal alcohol syndrome', 'FAS', 'FASD', 'MRI', 'DTI', 'MRS', 'neuroimaging',
      'children' and 'infants'. RESULTS: A total of 64 relevant articles were
      identified across all modalities. Overall, studies reported smaller total brain
      volume as well as smaller volume of both the white and grey matter in specific
      cortical regions. The most consistently reported structural MRI findings were
      alterations in the shape and volume of the corpus callosum, as well as smaller
      volume in the basal ganglia and hippocampi. The most consistent finding from
      diffusion tensor imaging studies was lower fractional anisotropy in the corpus
      callosum. Proton magnetic resonance spectroscopy studies are few to date, but
      showed altered neurometabolic profiles in the frontal and parietal cortex,
      thalamus and dentate nuclei. Resting-state functional MRI studies reported
      reduced functional connectivity between cortical and deep grey matter structures.
      Discussion There is a critical gap in the literature of MRI studies in alcohol
      exposed children under 5 years of age across all MRI modalities. The dynamic
      nature of brain maturation and appreciation of the effects of alcohol exposure on
      the developing trajectory of the structural and functional network argue for the
      prioritisation of studies that include a longitudinal approach to understanding
      this spectrum of effects and potential therapeutic time points.

PMID- 25780876
TI  - Design, synthesis, and biological evaluation of novel 2-((2-(4
      (substituted)phenylpiperazin-1-yl)ethyl)amino)-5'-N-ethylcarboxamidoadenosines as
      potent and selective agonists of the A2A adenosine receptor.
AB  - Stimulation of A2A adenosine receptors (AR) promotes anti-inflammatory responses
      in animal models of allergic rhinitis, asthma, chronic obstructive pulmonary
      disease, and rheumatic diseases. Herein we describe the results of a research
      program aimed at identifying potent and selective agonists of the A2AAR as
      potential anti-inflammatory agents. The recent crystallographic analysis of A2AAR
      agonists and antagonists in complex with the receptor provided key information on
      the structural determinants leading to receptor activation or blocking. In light
      of this, we designed a new series of 2-((4-aryl(alkyl)piperazin-1-yl)alkylamino)
      5'-N-ethylcarboxamidoadenosines with high A2AAR affinity, activation potency and
      selectivity obtained by merging distinctive structural elements of known agonists
      and antagonists of the investigated target. Docking-based SAR optimization
      allowed us to identify compound 42 as one of the most potent and selective A2A
      agonist discovered so far (Ki hA2AAR = 4.8 nM, EC50 hA2AAR = 4.9 nM, Ki hA1AR >
      10 000 nM, Ki hA3AR = 1487 nM, EC50 hA2BAR > 10 000 nM). 

PMID- 25780877
TI  - MicroRNAs and Asthma Regulation.
AB  - MicroRNAs participate in the regulation of asthma, the goal of this study is to
      summarize recent researches on the roles of microRNAs in the pathogenesis of
      asthma. A review of the English medical literatures was conducted by searching
      PubMed for studies concerning asthma and microRNAs. The results of the present
      study indicate that microRNAs play important roles in regulating asthma immune
      responses. MicroRNAs not only participate in determining DCs phenotype and then
      naive T lymphocyte differentiation, but also participate in the regulation of
      airway inflammation and airway remodeling in asthma. Furthermore, microRNAs are
      also shown to be targets for asthma therapy in the future. 

PMID- 25780878
TI  - The diagnosis of hyper immunoglobulin e syndrome based on project management.
AB  - Hyperimmunoglobulin E Syndrome (HIES) is a complex primary immunodeficiency
      characterized by both immunologic and non-immunologic manifestations. High serum
      IgE level, eosinophilia, eczema, recurrent skin and lung infections constitute
      the immunologic profile of HIES, whereas characteristic facial appearance,
      scoliosis, retained primary teeth, joint hyperextensibility, bone fractures
      following minimal trauma and craniosynostosis are the main non-immunologic
      manifestations. The diagnosis of HIES cannot be made by routine immunologic
      tests. As the main characteristic laboratory abnormalities of this syndrome are
      highly elevated serum IgE levels and eosinophilia; both features have a broad
      spectrum of differential diagnosis. The purpose of this essay was presenting the
      best way for diagnosis management of HIES. Based on the genetic reports of
      patients of the Center for Chronic Immunodeficiency (CCI) as a single center
      experience, and applying project management (PM) in health care research
      projects, we sought the best way for a rapid diagnosis of HIES. The combination
      of project management principles with immunologic and genetic knowledge to better
      define the laboratory and clinical diagnosis lead to an improvement of the
      management of patients with HIES. These results are shown in one "Decision Tree"
      which is based on 342 genetic reports of the CCI during the past ten years. It is
      necessary to facilitate the diagnostic analysis of suspected HIES patients;
      applying project management in health care research projects provides a better
      and more accurate diagnosis eventually leading to a better patients' care. This
      Abstract was presented at 16th Biennial Meeting of the European Society for
      Immunodeficiencies (ESID 2014), Prague, Czech Republic. 

PMID- 25780874
TI  - Chitin, chitosan, and its derivatives for wound healing: old and new materials.
AB  - Chitin (beta-(1-4)-poly-N-acetyl-D-glucosamine) is widely distributed in nature
      and is the second most abundant polysaccharide after cellulose. It is often
      converted to its more deacetylated derivative, chitosan. Previously, many reports
      have indicated the accelerating effects of chitin, chitosan, and its derivatives
      on wound healing. More recently, chemically modified or nano-fibrous chitin and
      chitosan have been developed, and their effects on wound healing have been
      evaluated. In this review, the studies on the wound-healing effects of chitin,
      chitosan, and its derivatives are summarized. Moreover, the development of
      adhesive-based chitin and chitosan are also described. The evidence indicates
      that chitin, chitosan, and its derivatives are beneficial for the wound healing
      process. More recently, it is also indicate that some nano-based materials from
      chitin and chitosan are beneficial than chitin and chitosan for wound healing.
      Clinical applications of nano-based chitin and chitosan are also expected. 

PMID- 25780879
TI  - Common aeroallergens in patients with asthma and allergic rhinitis living in
      southwestern part of Iran: based on skin prick test reactivity.
AB  - Aeroallergens continue to have a key role in the pathogenesis of asthma and
      allergic diseases and have recently received increased attention in medical
      research throughout the world. The prevalence of aeroallergens vary in different
      regions, depending on the type of climate. The aim of the present study was to
      determine prevalence of the sensitivity to aeroallergens among patients with
      asthma and allergic rhinitis (AR), based on skin prick test (SPT) reactivity in
      the province of Bushehr, Iran. In this cross-sectional study, 743 patients were
      enrolled. The participants had asthma and AR and reacted to at least one allergen
      with SPT. Skin prick test with standard extracts including house dust mites
      (HDMs), animal dander, molds and pollens were performed on patients according to
      the herbal geography of the area. The male to female ratio and mean age of the
      patients were 1.03 and 27.6+/- 15.4 year, respectively. Out of 567 patients with
      AR, the common aeroallergens were HDMs (88.5%), molds (82.9%), animal dander
      (79.5%), weeds (77.6%), trees (75.5%) and grass pollen (71.5%). Moreover, among
      176 patients with asthma, the prevalence of aeroallergens were HDMs (90.5 %),
      molds (80.7%), animal dander (77.5%), weeds (73.3%), trees (73.3%) and grass
      pollen (67.9%). The sensitivity to animal dander, Chenopodium album and Russian
      thistle pollens were significantly associated with the severity of AR. Moreover,
      sensitivity to animal dander such as cat and feather of birds, cockroach, Bermuda
      grass and Chenopodium album pollens were significantly associated with the
      severity of asthma. The results of this study revealed that HDM was the most
      common sensitizing aeroallergen in patients with asthma and AR. Molds and animal
      dander as indoor allergens were also common aeroallergens. We suggest that the
      hot weather and ambient humidity in the region may be the main cause of the
      change in the pattern of SPT reactivity. 

PMID- 25780880
TI  - Characterization of two pollen allergens of the London plane tree in Shanghai.
AB  - Platanus acerifolia, London plane tree, a significant source of airborne
      allergens, is widely grown in Shanghai and other cities in China. In recent
      decades, little has been known regarding the influence of the allergens on
      sensitizing the population in the Shanghai area. The aims of this study were to
      purify and characterize the two major allergens and to confirm the immunological
      activities of these pollen allergens in Shanghai. Crude extract was purified with
      a HiTrap SP column and a Sephedex G75 column. Immunodetection was performed with
      ELISA and immunoblotting. Following gel proteolytic digestion and mass
      spectrometry, the tandem MS (MS/MS) peptide mass fingerprint was obtained and the
      MASCOT search engine was used to identify the peptide. The accession number of
      the interesting homologous data and all the sequence information was acquired by
      an internet database and the evolutionary trees were drawn with Mega 4.0
      software. Two proteins with molecular weights of 43 kDa and 18 kDa were purified
      from P. acerifolia pollen extract. The purified proteins were identified as
      pollen allergen Pla a 1 and Pla a 2 via mass spectrometry. The proteins have
      immunological activities with human IgE antibodies. According to the ELISA
      results, 12% (5/41) of the subjects were sensitive to Pla a 1 and 9% (4/41) were
      sensitive to Pla a 2. Pla a 1 and Pla a 2 are thus important allergens for
      patients with an allergic reaction to P. acerifolia pollen in Shanghai. 

PMID- 25780881
TI  - Evaluation of the Effect of Ascorbic Acid Administration on Gene Expression Level
      of IL-6 and TNF-alpha Cytokines in Deceased Donors.
AB  - Brain death is associated with increased inflammatory cytokines levels and poor
      graft quality to transplant. We aimed to evaluate the impact of Ascorbic Acid
      (AA) on the inflammatory status of Brain-Dead Donors (BDDs). Forty BDDs were
      randomly divided into two groups. Donor treatment (n=20) consisted of 100 mg/kg
      AA infusion 6 hours before donor operation and subsequent infusion of 100
      mg/kg/p6h until organ removal. Blood samples were taken at three times, 6 hours
      before donor surgery (TP(1)), immediately after laparotomy (TP(2)), and before
      organ removal (TP(3)). Gene expression level and serum concentration of IL-6 and
      TNF-alpha cytokines were assessed by real-time PCR and ELISA methods. To
      investigate transplanted liver function, serum values of Aspartate
      Aminotransferase (AST), Alanine Aminotransferase (ALT), and Billirubin-Total were
      evaluated on the 1(st), 3(rd), and 10(th) postoperative days. We found a
      significant reduction in IL-6 mRNA expression ratio of TP(3) to TP(1) following
      AA application among BDDs. Despite the considerable decrease in treated donors
      regarding IL-6 mRNA expression ratio of TP(2) to TP(1), TP(3) to TP(2), and also
      TNF-alpha variations in these periods, the results were not significant.
      Regarding serum concentration of these cytokines, particularly IL-6, there was a
      decrease between TP(2) and TP(3) following AA application in the treated donors.
      Furthermore, a significant reduction was found in serum AST and ALT levels in the
      recipients of treated group on the 3(rd) day compared to the 1(st) day after
      transplantation. It seems that AA beneficially affects the inflammatory status of
      BDDs, resulting in improved primary allograft function.

PMID- 25780882
TI  - The Effect of IL-22 and IL-28 in Induction of Type 1 Regulatory T (Tr1) Cells.
AB  - Cytokines have been introduced as critical inducers in the development of Th
      subpopulations.Cytokines like IL-10 are involved in inducing regulatory T cells
      such as Type 1 regulatory T (Tr1) cells cells. IL-22 is a member of IL-10 family
      of cytokines, and IL-28A is a member of IFN-gamma family. In this study, cord
      blood mononuclear cells (CBMC) from normal healthy individuals were isolated by
      Ficoll and then naive T cells were purified by CD4+CD25+ Regulatory T cell
      Isolation kit. The effect of these two cytokines on production of IL-5, TGF-beta,
      IL-10, IL-4 and IFN-gamma cytokines from cord blood T cells was investigated to
      identify Tr1 cells as well as Th1 and Th2 polarization. Flow cytometric analysis
      showed that IL-28A and IL-22 were not effective in expression of IL-5 and TGF
      beta either alone or in synergy, but in view of IL-10, IL-4 and IFN-gamma, the
      results showed that IL-22 increased IL-10 and IL-4 but had a decreasing effect on
      IFN-gamma. The results showed that IL-28A was not effective in increasing or
      decreasing the level of IL-10, IL-4 and IFN-gamma. Therefore, according to these
      results, IL-22 and IL-28A were not effective in inducing Tr1 cells. 

PMID- 25780883
TI  - Expression and Purification of a Novel Computationally Designed Antigen for
      Simultaneously Detection of HTLV-1 and HBV Antibodies.
AB  - Computational tools are reliable alternatives to laborious work in chimeric
      protein design. In this study, a chimeric antigen was designed using
      computational techniques for simultaneous detection of anti-HTLV-I and anti-HBV
      in infected sera. Databases were searched for amino acid sequences of HBV/HLV-I
      diagnostic antigens. The immunodominant fragments were selected based on
      propensity scales. The diagnostic antigen was designed using these fragments.
      Secondary and tertiary structures were predicted and the B-cell epitopes were
      mapped on the surface of built model. The synthetic DNA coding antigen was sub
      cloned into pGS21a expression vector. SDS-PAGE analysis showed that glutathione
      fused antigen was highly expressed in E. coli BL21 (DE3) cells. The recombinant
      antigen was purified by nickel affinity chromatography. ELISA results showed that
      soluble antigen could specifically react with the HTLV-I and HBV infected sera.
      This specific antigen could be used as suitable agent for antibody-antigen based
      screening tests and can help clinicians in order to perform quick and precise
      screening of the HBV and HTLV-I infections. 

PMID- 25780884
TI  - Investigating the Effect of rs3783605 Single-nucleotide Polymorphism on the
      Activity of VCAM-1 Promoter in Human Umbilical Vein Endohelial Cells.
AB  - The interaction between immune cells and endothelial lining of blood vessels is
      vital in many processes such as inflammatory and immune responses as well as
      cancer cell metastasis. The expression level of VCAM-1 is regulated by many
      factors including the promoter activity that is possibly affected by the single
      nucleotide polymorphisms (SNPs) present in the promoter. There are previous
      reports suggesting an important role for rs3783605 at -420 position in the
      pathogenesis of VCAM1-associated diseases. This is possibly due to the effect of
      this SNP on promoter activity and gene expression. Therefore, present study was
      designed to investigate the effect of rs3783605 on the activity of VCAM-1 gene
      promoter in human umbilical vein endothelial cells (HUVEC). In this study, two
      appropriate expression vectors containing VCAM1 promoter with different alleles
      of rs3783605 were constructed to express the Green Fluorescent Protein (GFP).
      Expression vectors were transfected into HUVECs and their EGFP expression level
      was assessed by the fluorescent microscopy and real-time PCR. Bright green
      fluorescence was seen in the HUVECs transfected by expression vector containing
      CMV promoter. The expression level in the cells transfected by vector containing
      promoter with A allele of rs3783605 was 0.14888 folds and G allele was about
      0.37851 folds of cells transfected by vector having CMV promoter (p<0.001).
      Moreover, HUVECs transfected by G allele of rs3783605 showed about 2-fold higher
      transcriptional activity compared with the A allele, (p=0.049). Our findings
      showed that rs3783605 polymorphism may play a role in VCAM-1 gene expression.
      Therefore, it is likely that it may have an important role in the pathogenesis of
      VCAM1-associated diseases and tumor metastases. 

PMID- 25780885
TI  - Down-regulation of TLR2, 3, 9 and Signaling Mediators, MyD88 and TRIF, Gene
      Transcript Levels in Patients with Kawasaki Disease Treated with IVIG.
AB  - Kawasaki disease (KD) is an acute febrile systemic vasculitis of childhood
      characterized by elevated levels of inflammatory mediators at the acute stage.
      High-dose intravenous immunoglobulin (IVIG) is well accepted as a conventional
      therapy for KD. The aim of the present study was to determine the expression
      level of Toll like receptors (TLRs) and their corresponding signaling mediators
      in PBMCs of IVIG-treated KD patients. TLR2, 3, 9 and signaling mediators, MyD88
      and TRIF transcript levels were determined in PBMCs from 31 KD patients, before
      (acute phase), 2 weeks later (sub-acute phase) and 6 weeks later (convalescent
      phase) of IVIG therapy using real time PCR. The mean age of the patients was 3.6
      years and 65% of subjects were male and 35% were female. 20 age-matched
      irrelevant febrile patients and 20 healthy subjects were included as control
      groups. Elevated levels of TLR2, MyD88, and TRIF gene transcripts were observed
      in the PBMCs at acute phase of untreated KD patients in compression with normal
      subjects. IVIG therapy resulted in significant decrease in TLR2, 3 and 9 (60-90%)
      as well as MyD88 and TRIF (60-70%) transcripts following 2 and 6 weeks. With
      Regard to significant up-regulation of MyD88 and TRIF at the acute phase of KD,
      our findings suggest TLR signaling pathway potential in KD pathogenesis and may
      also support the assumption of an infectious background in KD. Down-regulation of
      TLR members and corresponding mediators in IVIG treated patient suggest general
      TLR pathway suppression as a novel anti-inflammatory mechanism of IVIG. 

PMID- 25780886
TI  - Cyclosporine A Suppresses the Activation of the Th17 Cells in Patients with
      Primary Sjogren's Syndrome.
AB  - Primary Sjogren's syndrome (pSS) is a common autoimmune disease involving
      abnormal Th17 activation. The aim of the current study was to investigate the
      immunosuppression effect of Cyclosporine A (Cys A), a potent immunosuppressor on
      the proliferation and activation of T cells, on the activation of Th17 cells.
      Blood samples from both inactive and active pSS patients as well as healthy
      controls were collected and serum and peripheral blood mononuclear cells (PBMCs)
      were collected and tested for IL-17 and RORgammat expression. Subsequently, PBMCs
      were treated in vitro with Cys A in a series of doses and incubation time and the
      effect of Cys A on inhibiting Th17 activation was tested by measuring IL-17 and
      RORgammat expression. IL-17 in both serum and PBMCs as well as RORgammat in PBMCs
      from active pSS patients were significantly elevated on both the mRNA and protein
      levels comparing to those from both inactive pSS patients and healthy controlCys
      A in the final concentration of 80ng/ml and the treatment time of 24h showed
      strong inhibition effect on the expression of IL-17 and RORgammat in PBMCs from
      active pSS patients. However, Cys A in various doses and incubation times did not
      show much impact on inhibiting IL-17 as well as RORgammat expression in PBMCs
      from healthy donors and inactive pSS patients. Cys A possesses the capability in
      immunosuppressing the activation of Th17 cells, suggesting that Cys A may be a
      potential treatment for pSS and maybe other autoimmune diseases. 

PMID- 25780887
TI  - Cytokines gene expression in newly diagnosed multiple sclerosis patients.
AB  - Multiple Sclerosis (MS) is characterized by multiple areas of inflammation,
      demyelination and neurodegeneration. Infiltrating Th1 CD4+ T cells secrete
      proinflammatory cytokines. They stimulate the release of some cytokines,
      expression of adhesion molecules and these cytokines may cause damage to the
      myelin sheath and axons. In this study, we analyzed plasma levels and gene
      expressions of five important cytokines in the new diagnosed MS Patients by ELISA
      and Real time PCR. PCR amplifications were performed to determine the IL-17, IL
      23, IL-10, IL-27 and TGF-beta mRNA expression levels using the SYBR Green PCR
      Kit. Our results showed significant decrease in IL-10, IL-27 and TGF-beta but
      there was no significant difference in the IL-17 and IL-23 between patients and
      healthy controls. Altogether, our results indicated that dysregulation of
      cytokines, mainly increased expression of pro-inflammatory cytokines and
      decreased expression of inhibitory cytokines occurred in MS patients. This study
      may shed light to the probable role of these cytokines in neurodegeneration
      mechanism and current or future use of cytokines in managing and treatment of
      multiple sclerosis. 

PMID- 25780888
TI  - HLA-G5 and G7 Isoforms in Pregnant Women.
AB  - Human leukocyte antigen-G which is an immune tolerance effecter molecule has an
      important role in the maintenance of fetus during pregnancy. Abortion is one of
      the complications of pregnancy period.  In this research, we have studied levels
      of HLA-G 5, HLA-G7 isoforms in the abortion-threatened pregnant women in
      comparison with controls. In a case-control study, 101 abortion-threatened women
      and 101 healthy pregnant women (healthy controls) with age range 21-32 years were
      studied. Gene expression of HLA-5 and HLA-7 isoforms was analyzed by real-time
      polymerase chain reaction after mRNA extraction and cDNA synthesis. The results
      indicated that HLA-G5 was significantly lower in abortion-threatened women in
      comparison with the control group whereas HLA-G7 was not significantly
      differentbetween the 2 groups. HLA-G is a vital molecule during pregnancy that
      can be a key factor in prevention of abortion. It is concluded that determination
      of HLA-G5 can be of value in pregnancy. 

PMID- 25780889
TI  - Vitamin D deficiency in chronic idiopathic urticaria.
AB  - Chronic urticaria is the most common skin diseases, characterized by chronic
      cutaneous lesions which severely debilitates patients in several aspects of their
      everyday life. Vitamin D is known to exert several actions in the immune system
      and to influence function and differentiation of mast cells, central role players
      in the pathogenesis of chronic idiopathic urticaria. This study was performed to
      evaluate the relationship between vitamin D levels and susceptibility to chronic
      idiopathic urticaria. One hundred and fourteen patients with chronic idiopathic
      urticaria were recruited in this study along with one hundred and eighty seven
      sex-matched and age-matched healthy volunteers as the control group. For each
      patient, urticaria activity score was calculated and autologous serum skin test
      was done. Vitamin D metabolic statue was measured in serum as 25 hydroxyvitamin D
      using enzyme immunoassay method. Patients with chronic idiopathic urticaria
      significantly showed lower levels of vitamin D. Vitamin D deficiency was
      significantly associated with increased susceptibility to chronic idiopathic
      urticaria. There was a significant positive correlation between vitamin D levels
      and urticaria activity score. This study showed that patients with chronic
      idiopathic urticaria had reduced levels of vitamin D, while vitamin D deficiency
      could increase susceptibility to chronic idiopathic urticaria.

PMID- 25780890
TI  - The local and systemic reactions due to sublingual immunotherapy: is anaphylaxis
      associated with therapy.

PMID- 25780891
TI  - Retraction announcement.

PMID- 25780893
TI  - No correlation between estimated and actual glomerular filtration rates in
      pediatric oncology patients.

PMID- 25780894
TI  - Into the pressure cooker: Student stress in college preparatory high schools.
AB  - PURPOSE: The goals of this study were to (1) measure psychological,
      physiological, and behavioral indicators of stress, (2) assess the relationship
      between stress and student attitudes, and (3) explore coping behaviors in
      response to stress, among a sample of students in two academically high-achieving
      environments. METHOD: Three hundred thirty-three students in grades 9 through 12
      from two college-preparatory high schools completed a cross-sectional online
      survey that included the Students' Life Satisfaction Scale, School Attitude
      Assessment Questionnaire-Revised, and assessments for stress-related indicators,
      including eating, sleeping and exercise, and strategies they utilized for coping
      with stress. RESULTS: Students reported a high prevalence of physical and
      psychological correlates of stress, and related unhealthy behaviors such as
      widespread and chronic sleep deprivation and rushed meals. CONCLUSIONS: The
      results suggest areas to focus attention for identifying and addressing
      maladaptive responses to stress among high-achieving student populations.

PMID- 25780896
TI  - CDC42 Gtpase Activation Affects Hela Cell DNA Repair and Proliferation Following
      UV Radiation-Induced Genotoxic Stress.
AB  - Cell division control protein 42 (CDC42) homolog is a small Rho GTPase enzyme
      that participates in such processes as cell cycle progression, migration,
      polarity, adhesion, and transcription. Recent studies suggest that CDC42 is a
      potent tumor suppressor in different tissues and is related to aging processes.
      Although DNA damage is crucial in aging, a potential role for CDC42 in genotoxic
      stress remains to be explored. Migration, survival/proliferation and DNA
      damage/repair experiments were performed to demonstrate CDC42 involvement in the
      recovery of HeLa cells exposed to ultraviolet radiation-induced stress. Sub-lines
      of HeLa cells ectopically expressing the constitutively active CDC42-V12 mutant
      were generated to examine whether different CDC42-GTP backgrounds might reflect
      different sensitivities to UV radiation. Our results show that CDC42 constitutive
      activation does not interfere with HeLa cell migration after UV radiation.
      However, the minor DNA damage exhibited by the CDC42-V12 mutant exposed to UV
      radiation most likely results in cell cycle arrest at the G2/M checkpoint and
      reduced proliferation and survival. HeLa cells and Mock clones, which express
      endogenous wild-type CDC42 and show normal activity, are more resistant to UV
      radiation. None of these effects are altered by pharmacological CDC42 inhibition.
      Finally, the phosphorylation status of the DNA damage response proteins gamma
      H2AX and p-Chk1 was found to be delayed and attenuated, respectively, in CDC42
      V12 clones. In conclusion, the sensitivity of HeLa cells to ultraviolet radiation
      increases with CDC42 over-activation due to inadequate DNA repair signaling,
      culminating in G2/M cell accumulation, which is translated into reduced cellular
      proliferation and survival.

PMID- 25780898
TI  - Prediction of small-for-gestational-age neonates: screening by uterine artery
      Doppler and mean arterial pressure at 35-37 weeks.
AB  - OBJECTIVE: To investigate the potential value of uterine artery (UtA) pulsatility
      index (PI) and mean arterial pressure (MAP) at 35-37 weeks' gestation in the
      prediction of delivery of small-for-gestational-age (SGA) neonates, in the
      absence of pre-eclampsia (PE). METHODS: This was a screening study in singleton
      pregnancies at 35-37 weeks, including 245 that delivered SGA neonates with birth
      weight < 5(th) percentile and 4876 cases unaffected by SGA, PE or gestational
      hypertension. Multivariable logistic regression analysis was used to determine if
      UtA-PI and MAP improved the prediction of SGA neonates provided by screening with
      maternal characteristics and medical history (maternal factors), and estimated
      fetal weight (EFW) from fetal head circumference, abdominal circumference and
      femur length. RESULTS: Compared to the normal group, the median multiple of the
      median (MoM) values of UtA-PI and MAP were significantly higher in the SGA <
      5(th) group. Combined screening by maternal factors, EFW Z-score, UtA-PI and MAP
      at 35-37 weeks predicted, at a 10% false-positive rate, 90%, 86% and 90% of SGA
      neonates with birth weight < 10(th) , < 5(th) and < 3(rd) percentiles,
      respectively, delivering < 2 weeks following assessment; the respective values
      for SGA delivering >= 37 weeks were 66%, 74% and 80%. Such performance was not
      significantly different from screening by maternal factors and EFW Z-score alone.
      CONCLUSION: Addition of UtA-PI and MAP to combined testing by maternal factors
      and fetal biometry at 35-37 weeks does not improve the performance of screening
      for delivery of SGA neonates.

PMID- 25780899
TI  - Surveillance direct laryngoscopy and bronchoscopy in children with
      tracheostomies.
AB  - OBJECTIVES/HYPOTHESIS: To determine utility of surveillance direct laryngoscopy
      and bronchoscopy (DLB) in children with chronic tracheostomies by examining the
      frequency of operative intervention in children undergoing an annual DLB. STUDY
      DESIGN: Retrospective medical record review and analysis of operative findings
      and interventions. METHODS: A retrospective chart review was conducted of all
      children with tracheostomies who underwent surveillance DLB between 2003 and 2012
      at a tertiary children's hospital. Charts were reviewed for demographics,
      indication for tracheotomy, symptoms prior to DLB, dates of DLB, and operative
      findings and interventions. RESULTS: A total of 489 patients underwent 1,094
      DLBs. Two hundred fifty-three DLBs (23%) were accompanied by preprocedural
      symptoms including bleeding; increased secretions; infection; and changes in
      ventilation requirement, swallow, or voice. Six hundred nineteen procedures (58%)
      required 817 interventions. Common interventions performed included debridement
      of granulation tissue (41%), tracheostomy tube exchange (27%), and subglottic
      dilation (10%). The presence of preprocedural symptoms and indication for
      tracheostomy did not predict need for intervention during DLB (P > .05).
      CONCLUSIONS: In pediatric tracheostomy patients undergoing surveillance DLB, most
      procedures (58%) required operative intervention for airway optimization. These
      data support our current practice of yearly surveillance DLB in asymptomatic
      pediatric tracheostomy patients and aim to facilitate the development of clinical
      practice guidelines regarding chronic tracheostomy care in pediatric patients.
      LEVEL OF EVIDENCE: 4

PMID- 25780900
TI  - Micellar electrokinetic chromatography method for measuring amino acid secretions
      from islets of Langerhans.
AB  - Islets of Langerhans are responsible for maintaining glucose homeostasis through
      regulated secretion of hormones and other factors. It is hypothesized that amino
      acids secreted from islets play a critical role in cell functionality and
      viability. For example, glutamate and gamma-aminobutyric acid have been proposed
      to work as paracrine signaling molecules within islets to coordinate the release
      of hormone secretion; other amino acids, such as glutamine, leucine, alanine, and
      arginine, have been shown to stimulate or potentiate glucose-stimulated insulin
      secretion. To characterize the potential roles that these small molecules may
      play in islet physiology, derivatization of amino acids in high-salt buffers
      commonly used in islet experiments with naphthalene-2,3-dicarboxaldehyde and MEKC
      separation conditions were optimized. The optimized conditions used d-norvaline
      as the internal standard and allowed quantification of 14 amino acids with LODs
      ranging from 0.2 to 7 nM. The RSDs of the migration times were 0.04-0.54% and the
      RSDs of the peak areas were 0.2-5.8% for the various amino acids. The effects of
      glucose and 2,4-dinitrophenol on amino acid secretions from islets were tested
      and a suppressive effect of glucose on gamma-aminobutyric acid release was
      observed, likely acting through adenosine triphosphate inactivation of glutamate
      decarboxylase. 

PMID- 25780902
TI  - Synthesis, characterization and cellular location of cytotoxic constitutional
      organometallic isomers of rhenium delivered on a cyanocobalmin scaffold.
AB  - Constitutional isomers of cyanocobalamin adducts based on a fluorescent rhenium
      tris-carbonyl diimine complex were prepared, characterized and tested against PC
      3 cancer cells. The adducts differ only in the relative binding position of the
      organometallic species which is either bound at the cyano or the 5'-hydroxo group
      of vitamin B12. When tested for their cytotoxic potency, the species showed IC50
      values in the low MUM rage. Upon conjugation to the vitamin an energy transfer
      process causes an extremely low quantum yield of fluorescence emission, making
      the conjugates unsuitable for fluorescence imaging. However, by exploiting the
      vibrational signature of the fac-[Re(CO)3](+) core, their cellular distribution
      was evaluated via FTIR spectromicroscopy. 

PMID- 25780903
TI  - Nutrients and pharmaceuticals removal from wastewater by culture and harvesting
      of Chlorella sorokiniana.
AB  - This work aimed to study both the removal of nutrients and pharmaceuticals,
      namely salicylic acid or paracetamol, from water by the culture of Chlorella
      sorokiniana. The removal of nutrients was nearly complete at the end of the batch
      culture; above 70% for nitrates and 89% for phosphates in the semicontinuous
      culture. The pharmaceuticals removal kinetics were 2.3 times greater for the
      salicylic acid than paracetamol, reaching volumetric efficiencies above 93% for
      salicylic acid in the semicontinuous culture. Finally, to separate the microalgae
      biomass from treated water, metal salts, synthetic polyelectrolytes and a
      biopolymer were tested as coagulants-flocculants. The best flocculation results
      were achieved with AlCl3 (95.23% with 200mgg(-1), 1min incubation time). However,
      given that resulting flocs had different characteristics, flocculants must be
      chosen on the basis of the subsequent use of the biomass. 

PMID- 25780904
TI  - An energy analysis of torrefaction for upgrading microalga residue as a solid
      fuel.
AB  - The torrefaction characteristics and energy utilization of microalga
      Chlamydomonas sp. JSC4 (C. sp. JSC4) residue under the combination of temperature
      and duration are studied by examining contour maps. The torrefaction temperature
      on the contour line of solid yield has a trend to linearly decrease with
      increasing duration. An index of relative energy efficiency (REE) is introduced
      to identify the performance of energy utilization for upgrading biomass. For a
      fixed energy yield, the optimal operation can be found to maximize the heating
      value of the biomass and minimize the solid yield. The energy utilization under
      the combination of a high temperature and a short duration is more efficient than
      that of a low temperature and a long duration. The maximum REE along the contour
      line of energy yield is always exhibited at the highest temperature (300 degrees
      C) where the energy efficiency can be enlarged by a factor of at least 2.36. 

PMID- 25780901
TI  - Proteomics analysis of bodily fluids in pancreatic cancer.
AB  - Proteomics study of pancreatic cancer using bodily fluids emphasizes biomarker
      discovery and clinical application, presenting unique prospect and challenges.
      Depending on the physiological nature of the bodily fluid and its proximity to
      pancreatic cancer, the proteomes of bodily fluids, such as pancreatic juice,
      pancreatic cyst fluid, blood, bile, and urine, can be substantially different in
      terms of protein constitution and the dynamic range of protein concentration.
      Thus, a comprehensive discovery and specific detection of cancer-associated
      proteins within these varied fluids is a complex task, requiring rigorous
      experiment design and a concerted approach. While major challenges still remain,
      fluid proteomics studies in pancreatic cancer to date have provided a wealth of
      information in revealing proteome alterations associated with pancreatic cancer
      in various bodily fluids. 

PMID- 25780905
TI  - Performance and microbial community of carbon nanotube fixed-bed microbial fuel
      cell continuously fed with hydrothermal liquefied cornstalk biomass.
AB  - Hydrothermal liquefaction (HTL) is a green technology for biomass pretreatment
      with the omission of hazardous chemicals. This study reports a novel integration
      of HTL and carbon nanotubes (CNTs) fixed-bed microbial fuel cell (FBMFC) for
      continuous electricity generation from cornstalk biomass. Two FBMFCs in parallel
      achieved similar performance fed with cornstalk hydrolysate at different organic
      loading rates (OLRs) (0.82-8.16g/L/d). About 80% of Chemical oxygen demand (COD)
      and Total organic carbon (TOC) was removed from low-Biochemical oxygen demand
      (BOD)/COD (0.16) cornstalk hydrolysate at 8.16g/L/d, whereas a maximum power
      density (680mW/m(3)) was obtained at 2.41g/L/d, and a smallest internal
      resistance (Rin) (28Omega) at 3.01g/L/d. Illumina MiSeq sequencing reveals the
      diverse microbial structure induced by the complex composition of cornstalk
      hydrolysate. Distinguished from Proteobacteria, which a number of exoelectrogens
      belong to, the identified dominant genus Rhizobium in FBMFC was closely related
      to degradation of cellulosic biomass. 

PMID- 25780906
TI  - Steam pretreatment of agricultural residues facilitates hemicellulose recovery
      while enhancing enzyme accessibility to cellulose.
AB  - The origins of lignocellulosic biomass and the pretreatment used to enhance
      enzyme accessibility to the cellulosic component are known to be strongly
      influenced by various substrate characteristics. To assess the impact that fibre
      properties might have on enzymatic hydrolysis, seven agricultural residues were
      characterised before and after steam pretreatment using a single pretreatment
      condition (190 degrees C, 5min, 3% SO2) previously shown to enhance fractionation
      and hydrolysis of the cellulosic component of corn stover. When the fibre length,
      width and coarseness, viscosity, water retention value and cellulose
      crystallinity were monitored, no clear correlation was observed between any
      single substrate characteristic and the substrate's ease of enzymatic hydrolysis.
      However, the amount of hemicellulose that was solubilised during pretreatment
      correlated (r(2)=0.98) with the effectiveness of enzyme hydrolysis of each
      pretreated substrate. Simons's staining, to measure the cellulose accessibility,
      showed good correlation (r(2)=0.83) with hemicellulose removal and the extent of
      enzymatic hydrolysis. 

PMID- 25780907
TI  - Does faecal diversion prevent morbidity after ileocecal resection for Crohn's
      disease? Retrospective series of 80 cases.
AB  - BACKGROUND: After ileocecal resection for Crohn's disease, a temporary faecal
      diversion is indicated in high-risk patients. The impact of a temporary stoma on
      post-operative morbidity has been poorly assessed so far. The aim was to analyse
      post-operative morbidity of temporary faecal diversion after ileocecal resection
      for Crohn's disease. METHODS: Patients undergoing temporary faecal diversion
      combined with ileocecal resection were retrospectively included. Patients
      presenting with complications were compared with patients with an uneventful post
      operative course, to identify any predictive factor for morbidity. RESULTS:
      Eighty faecal diversions were performed (43 males, 33.5 (18-75) years), including
      63 split stoma (79%) and 17 covering loop ileostomies (21%). Fifty-two patients
      (65%) presented with a perforating disease. Post-operative complications occurred
      in 15 patients (19%), 15 days after surgery (1-30). The main complications were
      intra-abdominal abscess (n = 6), functional renal failure (n = 6), fistula (n =
      2) and stomal prolapse (n = 2). Two patients required surgery. Previous bowel
      resections (60% versus 28%, P = 0.01) were significantly associated with post
      operative morbidity. CONCLUSIONS: Temporary faecal diversion is useful in high
      risk patients after ileocecal resection for Crohn's disease. Patients'
      information about post-operative risks remains an important issue. Risk factors
      for post-operative morbidity despite faecal diversion are previous bowel
      resections.

PMID- 25780908
TI  - Mechanical and microstructural investigation of the cyclic behavior of human
      amnion.
AB  - The structural and mechanical integrity of amnion is essential to prevent preterm
      premature rupture (PPROM) of the fetal membrane. In this study, the mechanical
      response of human amnion to repeated loading and the microstructural mechanisms
      determining its behavior were investigated. Inflation and uniaxial cyclic tests
      were combined with corresponding in situ experiments in a multiphoton microscope
      (MPM). Fresh unfixed amnion was imaged during loading and changes in thickness
      and collagen orientation were quantified. Mechanical and in situ experiments
      revealed differences between the investigated configurations in the deformation
      and microstructural mechanisms. Repeated inflation induces a significant but
      reversible volume change and is characterized by high energy dissipation. Under
      uniaxial tension, volume reduction is associated with low energy, unrecoverable
      in-plane fiber reorientation. 

PMID- 25780910
TI  - Large-scale transportation network congestion evolution prediction using deep
      learning theory.
AB  - Understanding how congestion at one location can cause ripples throughout large
      scale transportation network is vital for transportation researchers and
      practitioners to pinpoint traffic bottlenecks for congestion mitigation.
      Traditional studies rely on either mathematical equations or simulation
      techniques to model traffic congestion dynamics. However, most of the approaches
      have limitations, largely due to unrealistic assumptions and cumbersome parameter
      calibration process. With the development of Intelligent Transportation Systems
      (ITS) and Internet of Things (IoT), transportation data become more and more
      ubiquitous. This triggers a series of data-driven research to investigate
      transportation phenomena. Among them, deep learning theory is considered one of
      the most promising techniques to tackle tremendous high-dimensional data. This
      study attempts to extend deep learning theory into large-scale transportation
      network analysis. A deep Restricted Boltzmann Machine and Recurrent Neural
      Network architecture is utilized to model and predict traffic congestion
      evolution based on Global Positioning System (GPS) data from taxi. A numerical
      study in Ningbo, China is conducted to validate the effectiveness and efficiency
      of the proposed method. Results show that the prediction accuracy can achieve as
      high as 88% within less than 6 minutes when the model is implemented in a Graphic
      Processing Unit (GPU)-based parallel computing environment. The predicted
      congestion evolution patterns can be visualized temporally and spatially through
      a map-based platform to identify the vulnerable links for proactive congestion
      mitigation. 

PMID- 25780909
TI  - AUY922 effectively overcomes MET- and AXL-mediated resistance to EGFR-TKI in lung
      cancer cells.
AB  - The activation of bypass signals, such as MET and AXL, has been identified as a
      possible mechanism of EGFR-TKI resistance. Because various oncoproteins depend on
      HSP90 for maturation and stability, we investigated the effects of AUY922, a
      newly developed non-geldanamycin class HSP90 inhibitor, in lung cancer cells with
      MET- and AXL-mediated resistance. We established resistant cell lines with HCC827
      cells harboring an exon 19-deletion mutation in of the EGFR gene via long-term
      exposure to increasing concentrations of gefitinib and erlotinib (HCC827/GR and
      HCC827/ER, respectively). HCC827/GR resistance was mediated by MET activation,
      whereas AXL activation caused resistance in HCC827/ER cells. AUY922 treatment
      effectively suppressed proliferation and induced cell death in both resistant
      cell lines. Accordingly, the downregulation of EGFR, MET, and AXL led to
      decreased Akt activation. The inhibitory effects of AUY922 on each receptor were
      confirmed in gene-transfected LK2 cells. AUY922 also effectively controlled tumor
      growth in xenograft mouse models containing HCC827/GR and HCC827/ER cells. In
      addition, AUY922 reduced invasion and migration by both types of resistant cells.
      Our study findings thus show that AUY922 is a promising therapeutic option for
      MET- and AXL-mediated resistance to EGFR-TKI in lung cancer. 

PMID- 25780911
TI  - Genetic interaction between Tmprss2-ERG gene fusion and Nkx3.1-loss does not
      enhance prostate tumorigenesis in mouse models.
AB  - Gene fusions involving ETS family transcription factors (mainly TMPRSS2-ERG and
      TMPRSS2-ETV1 fusions) have been found in ~50% of human prostate cancer cases.
      Although expression of TMPRSS2-ERG or TMPRSS2-ETV1 fusion alone is insufficient
      to initiate prostate tumorigenesis, they appear to sensitize prostate epithelial
      cells for cooperation with additional oncogenic mutations to drive frank prostate
      adenocarcinoma. To search for such ETS-cooperating oncogenic events, we focused
      on a well-studied prostate tumor suppressor NKX3.1, as loss of NKX3.1 is another
      common genetic alteration in human prostate cancer. Previous studies have shown
      that deletions at 8p21 (harboring NKX3.1) and 21q22 (resulting in TMPRSS2-ERG
      fusion) were both present in a subtype of prostate cancer cases, and that ERG can
      lead to epigenetic silencing of NKX3.1 in prostate cancer cells, whereas NKX3.1
      can in turn negatively regulate TMPRSS2-ERG fusion expression via suppression of
      the TMPRSS2 promoter activity. We recently generated knockin mouse models for
      TMPRSS2-ERG and TMPRSS2-ETV1 fusions, utilizing the endogenous Tmprss2 promoter.
      We crossed these knockin models to an Nkx3.1 knockout mouse model. In Tmprss2
      ERG;Nkx3.1+/- (or -/-) male mice, although we observed a slight but significant
      upregulation of Tmprss2-ERG fusion expression upon Nkx3.1 loss, we did not detect
      any significant cooperation between these two genetic events to enhance prostate
      tumorigenesis in vivo. Furthermore, retrospective analysis of a previously
      published human prostate cancer dataset revealed that within ERG-overexpressing
      prostate cancer cases, NKX3.1 loss or deletion did not predict biochemical
      relapse after radical prostatectomy. Collectively, these data suggest that
      although TMPRSS2-ERG fusion and loss of NKX3.1 are among the most common
      mutational events found in prostate cancer, and although each of them can
      sensitize prostate epithelial cells for cooperating with other oncogenic events,
      these two events themselves do not appear to cooperate at a significant level in
      vivo to enhance prostate tumorigenesis. 

PMID- 25780912
TI  - Comprehensive model of annual plankton succession based on the whole-plankton
      time series approach.
AB  - Ecological succession provides a widely accepted description of seasonal changes
      in phytoplankton and mesozooplankton assemblages in the natural environment, but
      concurrent changes in smaller (i.e. microbes) and larger (i.e. macroplankton)
      organisms are not included in the model because plankton ranging from bacteria to
      jellies are seldom sampled and analyzed simultaneously. Here we studied, for the
      first time in the aquatic literature, the succession of marine plankton in the
      whole-plankton assemblage that spanned 5 orders of magnitude in size from
      microbes to macroplankton predators (not including fish or fish larvae, for which
      no consistent data were available). Samples were collected in the northwestern
      Mediterranean Sea (Bay of Villefranche) weekly during 10 months. Simultaneously
      collected samples were analyzed by flow cytometry, inverse microscopy, FlowCam,
      and ZooScan. The whole-plankton assemblage underwent sharp reorganizations that
      corresponded to bottom-up events of vertical mixing in the water-column, and its
      development was top-down controlled by large gelatinous filter feeders and
      predators. Based on the results provided by our novel whole-plankton assemblage
      approach, we propose a new comprehensive conceptual model of the annual plankton
      succession (i.e. whole plankton model) characterized by both stepwise stacking of
      four broad trophic communities from early spring through summer, which is a new
      concept, and progressive replacement of ecological plankton categories within the
      different trophic communities, as recognised traditionally. 

PMID- 25780914
TI  - Ocean acidification may aggravate social-ecological trade-offs in coastal
      fisheries.
AB  - Ocean Acidification (OA) will influence marine ecosystems by changing species
      abundance and composition. Major effects are described for calcifying organisms,
      which are significantly impacted by decreasing pH values. Direct effects on
      commercially important fish are less well studied. The early life stages of fish
      populations often lack internal regulatory mechanisms to withstand the effects of
      abnormal pH. Negative effects can be expected on growth, survival, and
      recruitment success. Here we study Norwegian coastal cod, one of the few stocks
      where such a negative effect was experimentally quantified, and develop a
      framework for coupling experimental data on OA effects to ecological-economic
      fisheries models. In this paper, we scale the observed physiological responses to
      the population level by using the experimentally determined mortality rates as
      part of the stock-recruitment relationship. We then use an ecological-economic
      optimization model, to explore the potential effect of rising CO2 concentration
      on ecological (stock size), economic (profits), consumer-related (harvest) and
      social (employment) indicators, with scenarios ranging from present day
      conditions up to extreme acidification. Under the assumptions of our model,
      yields and profits could largely be maintained under moderate OA by adapting
      future fishing mortality (and related effort) to changes owing to altered pH.
      This adaptation comes at the costs of reduced stock size and employment, however.
      Explicitly visualizing these ecological, economic and social tradeoffs will help
      in defining realistic future objectives. Our results can be generalized to any
      stressor (or stressor combination), which is decreasing recruitment success. The
      main findings of an aggravation of trade-offs will remain valid. This seems to be
      of special relevance for coastal stocks with limited options for migration to
      avoid unfavorable future conditions and subsequently for coastal fisheries, which
      are often small scale local fisheries with limited operational ranges. 

PMID- 25780913
TI  - Modeling the dynamics of Plasmodium vivax infection and hypnozoite reactivation
      in vivo.
AB  - The dynamics of Plasmodium vivax infection is characterized by reactivation of
      hypnozoites at varying time intervals. The relative contribution of new P. vivax
      infection and reactivation of dormant liver stage hypnozoites to initiation of
      blood stage infection is unclear. In this study, we investigate the contribution
      of new inoculations of P. vivax sporozoites to primary infection versus
      reactivation of hypnozoites by modeling the dynamics of P. vivax infection in
      Thailand in patients receiving treatment for either blood stage infection alone
      (chloroquine), or the blood and liver stages of infection (chloroquine +
      primaquine). In addition, we also analysed rates of infection in a study in Papua
      New Guinea (PNG) where patients were treated with either artesunate, or
      artesunate + primaquine. Our results show that up to 96% of the P. vivax
      infection is due to hypnozoite reactivation in individuals living in endemic
      areas in Thailand. Similar analysis revealed the around 70% of infections in the
      PNG cohort were due to hypnozoite reactivation. We show how the age of the
      cohort, primaquine drug failure, and seasonality may affect estimates of the
      ratio of primary P. vivax infection to hypnozoite reactivation. Modeling of P.
      vivax primary infection and hypnozoite reactivation provides important insights
      into infection dynamics, and suggests that 90-96% of blood stage infections arise
      from hypnozoite reactivation. Major differences in infection kinetics between
      Thailand and PNG suggest the likelihood of drug failure in PNG.

PMID- 25780915
TI  - Coupled biomechanical response of the cornea assessed by non-contact tonometry. A
      simulation study.
AB  - The mechanical response of the cornea subjected to a non-contact air-jet
      tonometry diagnostic test represents an interplay between its geometry, the
      corneal material behavior and the loading. The objective is to study this
      interplay to better understand and interpret the results obtained with a non
      contact tonometry test. A patient-specific finite element model of a healthy eye,
      accounting for the load free configuration, was used. The corneal tissue was
      modeled as an anisotropic hyperelastic material with two preferential directions.
      Three different sets of parameters within the human experimental range obtained
      from inflation tests were considered. The influence of the IOP was studied by
      considering four pressure levels (10-28 mmHg) whereas the influence of corneal
      thickness was studied by inducing a uniform variation (300-600 microns). A
      Computer Fluid Dynamics (CFD) air-jet simulation determined pressure loading
      exerted on the anterior corneal surface. The maximum apex displacement showed a
      linear variation with IOP for all materials examined. On the contrary, the
      maximum apex displacement followed a cubic relation with corneal thickness. In
      addition, a significant sensitivity of the apical displacement to the corneal
      stiffness was also obtained. Explanation to this behavior was found in the fact
      that the cornea experiences bending when subjected to an air-puff loading,
      causing the anterior surface to work in compression whereas the posterior surface
      works in tension. Hence, collagen fibers located at the anterior surface do not
      contribute to load bearing. Non-contact tonometry devices give useful information
      that could be misleading since the corneal deformation is the result of the
      interaction between the mechanical properties, IOP, and geometry. Therefore, a
      non-contact tonometry test is not sufficient to evaluate their individual
      contribution and a complete in-vivo characterization would require more than one
      test to independently determine the membrane and bending corneal behavior. 

PMID- 25780916
TI  - Characterizing social media metrics of scholarly papers: the effect of document
      properties and collaboration patterns.
AB  - A number of new metrics based on social media platforms--grouped under the term
      "altmetrics"--have recently been introduced as potential indicators of research
      impact. Despite their current popularity, there is a lack of information
      regarding the determinants of these metrics. Using publication and citation data
      from 1.3 million papers published in 2012 and covered in Thomson Reuters' Web of
      Science as well as social media counts from Altmetric.com, this paper analyses
      the main patterns of five social media metrics as a function of document
      characteristics (i.e., discipline, document type, title length, number of pages
      and references) and collaborative practices and compares them to patterns known
      for citations. Results show that the presence of papers on social media is low,
      with 21.5% of papers receiving at least one tweet, 4.7% being shared on Facebook,
      1.9% mentioned on blogs, 0.8% found on Google+ and 0.7% discussed in mainstream
      media. By contrast, 66.8% of papers have received at least one citation. Our
      findings show that both citations and social media metrics increase with the
      extent of collaboration and the length of the references list. On the other hand,
      while editorials and news items are seldom cited, it is these types of document
      that are the most popular on Twitter. Similarly, while longer papers typically
      attract more citations, an opposite trend is seen on social media platforms.
      Finally, contrary to what is observed for citations, it is papers in the Social
      Sciences and humanities that are the most often found on social media platforms.
      On the whole, these findings suggest that factors driving social media and
      citations are different. Therefore, social media metrics cannot actually be seen
      as alternatives to citations; at most, they may function as complements to other
      type of indicators.

PMID- 25780917
TI  - Toddlers favor communicatively presented information over statistical reliability
      in learning about artifacts.
AB  - Observed associations between events can be validated by statistical information
      of reliability or by testament of communicative sources. We tested whether
      toddlers learn from their own observation of efficiency, assessed by statistical
      information on reliability of interventions, or from communicatively presented
      demonstration, when these two potential types of evidence of validity of
      interventions on a novel artifact are contrasted with each other. Eighteen-month
      old infants observed two adults, one operating the artifact by a method that was
      more efficient (2/3 probability of success) than that of the other (1/3
      probability of success). Compared to the Baseline condition, in which
      communicative signals were not employed, infants tended to choose the less
      reliable method to operate the artifact when this method was demonstrated in a
      communicative manner in the Experimental condition. This finding demonstrates
      that, in certain circumstances, communicative sanctioning of reliability may
      override statistical evidence for young learners. Such a bias can serve fast and
      efficient transmission of knowledge between generations. 

PMID- 25780918
TI  - Correction: deciphering the genetic programme triggering timely and spatially
      regulated chitin deposition.

PMID- 25780919
TI  - Correction: spinal cord transection-induced allodynia in rats - behavioral,
      physiopathological and pharmacological characterization.

PMID- 25780920
TI  - Nfix expression critically modulates early B lymphopoiesis and myelopoiesis.
AB  - The commitment of stem and progenitor cells toward specific hematopoietic
      lineages is tightly controlled by a number of transcription factors that regulate
      differentiation programs via the expression of lineage restricting genes. Nuclear
      factor one (NFI) transcription factors are important in regulating hematopoiesis
      and here we report an important physiological role of NFIX in B- and myeloid
      lineage commitment and differentiation. We demonstrate that NFIX acts as a
      regulator of lineage specification in the haematopoietic system and the
      expression of Nfix was transcriptionally downregulated as B cells commit and
      differentiate, whilst maintained in myeloid progenitor cells. Ectopic Nfix
      expression in vivo blocked early B cell development stage, coincident with the
      stage of its downregulation. Furthermore, loss of Nfix resulted in the
      perturbation of myeloid and lymphoid cell differentiation, and a skewing of gene
      expression involved in lineage fate determination. Nfix was able to promote
      myeloid differentiation of total bone marrow cells under B cell specific culture
      conditions but not when expressed in the hematopoietic stem cell (HSPC),
      consistent with its role in HSPC survival. The lineage choice determined by Nfix
      correlated with transcriptional changes in a number of genes, such as E2A, C/EBP,
      and Id genes. These data highlight a novel and critical role for NFIX
      transcription factor in hematopoiesis and in lineage specification. 

PMID- 25780922
TI  - On the relation between the small world structure and scientific activities.
AB  - The modern science has become more complex and interdisciplinary in its nature
      which might encourage researchers to be more collaborative and get engaged in
      larger collaboration networks. Various aspects of collaboration networks have
      been examined so far to detect the most determinant factors in knowledge creation
      and scientific production. One of the network structures that recently attracted
      much theoretical attention is called small world. It has been suggested that
      small world can improve the information transmission among the network actors. In
      this paper, using the data on 12 periods of journal publications of Canadian
      researchers in natural sciences and engineering, the co-authorship networks of
      the researchers are created. Through measuring small world indicators, the small
      worldiness of the mentioned network and its relation with researchers'
      productivity, quality of their publications, and scientific team size are
      assessed. Our results show that the examined co-authorship network strictly
      exhibits the small world properties. In addition, it is suggested that in a small
      world network researchers expand their team size through getting connected to
      other experts of the field. This team size expansion may result in higher
      productivity of the whole team as a result of getting access to new resources,
      benefitting from the internal referring, and exchanging ideas among the team
      members. Moreover, although small world network is positively correlated with the
      quality of the articles in terms of both citation count and journal impact
      factor, it is negatively related with the average productivity of researchers in
      terms of the number of their publications. 

PMID- 25780921
TI  - Identification and characterization of PERK activators by phenotypic screening
      and their effects on NRF2 activation.
AB  - Endoplasmic reticulum stress plays a critical role to restore the homeostasis of
      protein production in eukaryotic cells. This vital process is hence involved in
      many types of diseases including COPD. PERK, one branch in the ER stress
      signaling pathways, has been reported to activate NRF2 signaling pathway, a known
      protective response to COPD. Based on this scientific rationale, we aimed to
      identify PERK activators as a mechanism to achieve NRF2 activation. In this
      report, we describe a phenotypic screening assay to identify PERK activators.
      This assay measures phosphorylation of GFP-tagged eIF2alpha upon PERK activation
      via a cell-based LanthaScreen technology. To obtain a robust assay with
      sufficient signal to background and low variation, multiple parameters were
      optimized including GFP-tagged eIF2alpha BacMam concentration, cell density and
      serum concentration. The assay was validated by a tool compound, Thapsigargin,
      which induces phosphorylation of eIF2alpha. In our assay, this compound showed
      maximal signal window of approximately 2.5-fold with a pEC50 of 8.0, consistent
      with literature reports. To identify novel PERK activators through
      phosphorylation of eIF2alpha, a focused set of 8,400 compounds was screened in
      this assay at 10 uM. A number of hits were identified and validated. The
      molecular mechanisms for several selected hits were further characterized in
      terms of PERK activation and effects on PERK downstream components. Specificity
      of these compounds in activating PERK was demonstrated with a PERK specific
      inhibitor and in PERK knockout mouse embryonic fibroblast (MEF) cells. In
      addition, these hits showed NRF2-dependent anti-oxidant gene induction. In
      summary, our phenotypic screening assay is demonstrated to be able to identify
      PERK specific activators. The identified PERK activators could potentially be
      used as chemical probes to further investigate this pathway as well as the link
      between PERK activation and NRF2 pathway activation. 

PMID- 25780923
TI  - Quantitative structure-property relationship (QSPR) modeling of drug-loaded
      polymeric micelles via genetic function approximation.
AB  - Self-assembled nano-micelles of amphiphilic polymers represent a novel anticancer
      drug delivery system. However, their full clinical utilization remains
      challenging because the quantitative structure-property relationship (QSPR)
      between the polymer structure and the efficacy of micelles as a drug carrier is
      poorly understood. Here, we developed a series of QSPR models to account for the
      drug loading capacity of polymeric micelles using the genetic function
      approximation (GFA) algorithm. These models were further evaluated by internal
      and external validation and a Y-randomization test in terms of stability and
      generalization, yielding an optimization model that is applicable to an expanded
      materials regime. As confirmed by experimental data, the relationship between
      microstructure and drug loading capacity can be well-simulated, suggesting that
      our models are readily applicable to the quantitative evaluation of the drug
      loading capacity of polymeric micelles. Our work may offer a pathway to the
      design of formulation experiments. 

PMID- 25780924
TI  - Using Massive Parallel Sequencing for the development, validation, and
      application of population genetics markers in the invasive bivalve zebra mussel
      (Dreissena polymorpha).
AB  - The zebra mussel (Dreissena polymorpha, Pallas, 1771) is one of the most invasive
      species of freshwater bivalves, due to a combination of biological and
      anthropogenic factors. Once this species has been introduced to a new area,
      individuals form dense aggregations that are very difficult to remove, leading to
      many adverse socioeconomic and ecological consequences. In this study, we
      identified, tested, and validated a new set of polymorphic microsatellite loci
      (also known as SSRs, Single Sequence Repeats) using a Massive Parallel Sequencing
      (MPS) platform. After several pruning steps, 93 SSRs could potentially be
      amplified. Out of these SSRs, 14 were polymorphic, producing a polymorphic yield
      of 15.05%. These 14 polymorphic microsatellites were fully validated in a first
      approximation of the genetic population structure of D. polymorpha in the Iberian
      Peninsula. Based on this polymorphic yield, we propose a criterion for
      establishing the number of SSRs that require validation in similar species,
      depending on the final use of the markers. These results could be used to
      optimize MPS approaches in the development of microsatellites as genetic markers,
      which would reduce the cost of this process. 

PMID- 25780925
TI  - Elucidation of sigma factor-associated networks in Pseudomonas aeruginosa reveals
      a modular architecture with limited and function-specific crosstalk.
AB  - Sigma factors are essential global regulators of transcription initiation in
      bacteria which confer promoter recognition specificity to the RNA polymerase core
      enzyme. They provide effective mechanisms for simultaneously regulating
      expression of large numbers of genes in response to challenging conditions, and
      their presence has been linked to bacterial virulence and pathogenicity. In this
      study, we constructed nine his-tagged sigma factor expressing and/or deletion
      mutant strains in the opportunistic pathogen Pseudomonas aeruginosa. To uncover
      the direct and indirect sigma factor regulons, we performed mRNA profiling, as
      well as chromatin immunoprecipitation coupled to high-throughput sequencing. We
      furthermore elucidated the de novo binding motif of each sigma factor, and
      validated the RNA- and ChIP-seq results by global motif searches in the proximity
      of transcriptional start sites (TSS). Our integrated approach revealed a highly
      modular network architecture which is composed of insulated functional sigma
      factor modules. Analysis of the interconnectivity of the various sigma factor
      networks uncovered a limited, but highly function-specific, crosstalk which
      orchestrates complex cellular processes. Our data indicate that the modular
      structure of sigma factor networks enables P. aeruginosa to function adequately
      in its environment and at the same time is exploited to build up higher-level
      functions by specific interconnections that are dominated by a participation of
      RpoN. 

PMID- 25780927
TI  - The quorum sensing peptides PhrG, CSP and EDF promote angiogenesis and invasion
      of breast cancer cells in vitro.
AB  - The role of the human microbiome on cancer progression remains unclear.
      Therefore, in this study, we investigated the influence of some quorum sensing
      peptides, produced by diverse commensal or pathogenic bacteria, on breast cancer
      cell invasion and thus cancer outcome. Based on microscopy, transcriptome and
      Chick Chorioallantoic Membrane (CAM) analyses, four peptides (PhrG from B.
      subtilis, CSP from S. mitis and EDF from E. coli, together with its tripeptide
      analogue) were found to promote tumour cell invasion and angiogenesis, thereby
      potentially influencing tumour metastasis. Our results offer not only new
      insights on the possible role of the microbiome, but also further opportunities
      in cancer prevention and therapy by competing with these endogenous molecules
      and/or by modifying people's life style. 

PMID- 25780926
TI  - Dynamic regulation of a cell adhesion protein complex including CADM1 by
      combinatorial analysis of FRAP with exponential curve-fitting.
AB  - Protein components of cell adhesion machinery show continuous renewal even in the
      static state of epithelial cells and participate in the formation and maintenance
      of normal epithelial architecture and tumor suppression. CADM1 is a tumor
      suppressor belonging to the immunoglobulin superfamily of cell adhesion molecule
      and forms a cell adhesion complex with an actin-binding protein, 4.1B, and a
      scaffold protein, MPP3, in the cytoplasm. Here, we investigate dynamic regulation
      of the CADM1-4.1B-MPP3 complex in mature cell adhesion by fluorescence recovery
      after photobleaching (FRAP) analysis. Traditional FRAP analysis were performed
      for relatively short period of around 10 min. Here, thanks to recent advances in
      the sensitive laser detector systems, we examine FRAP of CADM1 complex for longer
      period of 60 min and analyze the recovery with exponential curve-fitting to
      distinguish the fractions with different diffusion constants. This approach
      reveals that the fluorescence recovery of CADM1 is fitted to a single exponential
      function with a time constant (tau) of approximately 16 min, whereas 4.1B and
      MPP3 are fitted to a double exponential function with two taus of approximately
      40-60 sec and 16 min. The longer tau is similar to that of CADM1, suggesting that
      4.1B and MPP3 have two distinct fractions, one forming a complex with CADM1 and
      the other present as a free pool. Fluorescence loss in photobleaching analysis
      supports the presence of a free pool of these proteins near the plasma membrane.
      Furthermore, double exponential fitting makes it possible to estimate the ratio
      of 4.1B and MPP3 present as a free pool and as a complex with CADM1 as
      approximately 3:2 and 3:1, respectively. Our analyses reveal a central role of
      CADM1 in stabilizing the complex with 4.1B and MPP3 and provide insight in the
      dynamics of adhesion complex formation.

PMID- 25780928
TI  - Analysis of neurogenesis during experimental autoimmune encephalomyelitis reveals
      pitfalls of bioluminescence imaging.
AB  - Bioluminescence imaging is a sensitive approach for longitudinal neuroimaging.
      Transgenic mice expressing luciferase under the promoter of doublecortin (DCX
      luc), a specific marker of neuronal progenitor cells (NPC), allow monitoring of
      neurogenesis in living mice. Since the extent and time course of neurogenesis
      during autoimmune brain inflammation are controversial, we investigated
      neurogenesis in MOG-peptide induced experimental allergic encephalomyelitis (EAE)
      using DCX-luc reporter mice. We observed a marked, 2- to 4-fold increase of the
      bioluminescence signal intensity 10 days after EAE induction and a gradual
      decline 1-2 weeks thereafter. In contrast, immunostaining for DCX revealed no
      differences between EAE and control mice 2 and 4 weeks after immunization in
      zones of adult murine neurogenesis such as the dentate gyrus. Ex vivo
      bioluminescence imaging showed similar luciferase expression in brain homogenates
      of EAE and control animals. Apart from complete immunization including MOG
      peptide also incomplete immunization with complete Freund's adjuvant and
      pertussis toxin resulted in a rapid increase of the in vivo bioluminescence
      signal. Blood-brain barrier (BBB) leakage was demonstrated 10 days after both
      complete and incomplete immunization and might explain the increased
      bioluminescence signal in vivo. We conclude, that acute autoimmune inflammation
      in EAE does not alter neurogenesis, at least at the stage of DCX-expressing NPC.
      Effects of immunization on the BBB integrity must be considered when luciferase
      is used as a reporter within the CNS during the active stage of EAE. Models with
      stable CNS-restricted luciferase expression could serve as technically convenient
      way to evaluate BBB integrity in a longitudinal manner. 

PMID- 25780930
TI  - Rarity-weighted richness: a simple and reliable alternative to integer
      programming and heuristic algorithms for minimum set and maximum coverage
      problems in conservation planning.
AB  - Here we report that prioritizing sites in order of rarity-weighted richness (RWR)
      is a simple, reliable way to identify sites that represent all species in the
      fewest number of sites (minimum set problem) or to identify sites that represent
      the largest number of species within a given number of sites (maximum coverage
      problem). We compared the number of species represented in sites prioritized by
      RWR to numbers of species represented in sites prioritized by the Zonation
      software package for 11 datasets in which the size of individual planning units
      (sites) ranged from <1 ha to 2,500 km2. On average, RWR solutions were more
      efficient than Zonation solutions. Integer programming remains the only
      guaranteed way find an optimal solution, and heuristic algorithms remain superior
      for conservation prioritizations that consider compactness and multiple near
      optimal solutions in addition to species representation. But because RWR can be
      implemented easily and quickly in R or a spreadsheet, it is an attractive
      alternative to integer programming or heuristic algorithms in some conservation
      prioritization contexts. 

PMID- 25780929
TI  - Functional analysis of sirtuin genes in multiple Plasmodium falciparum strains.
AB  - Plasmodium falciparum, the causative agent of severe human malaria, employs
      antigenic variation to avoid host immunity. Antigenic variation is achieved by
      transcriptional switching amongst polymorphic var genes, enforced by epigenetic
      modification of chromatin. The histone-modifying 'sirtuin' enzymes PfSir2a and
      PfSir2b have been implicated in this process. Disparate patterns of var
      expression have been reported in patient isolates as well as in cultured strains.
      We examined var expression in three commonly used laboratory strains (3D7, NF54
      and FCR-3) in parallel. NF54 parasites express significantly lower levels of var
      genes compared to 3D7, despite the fact that 3D7 was originally a clone of the
      NF54 strain. To investigate whether this was linked to the expression of
      sirtuins, genetic disruption of both sirtuins was attempted in all three strains.
      No dramatic changes in var gene expression occurred in NF54 or FCR-3 following
      PfSir2b disruption, contrasting with previous observations in 3D7. In 3D7,
      complementation of the PfSir2a genetic disruption resulted in a significant
      decrease in previously-elevated var gene expression levels, but with the
      continued expression of multiple var genes. Finally, rearranged chromosomes were
      observed in the 3D7 PfSir2a knockout line. Our results focus on the potential for
      parasite genetic background to contribute to sirtuin function in regulating
      virulence gene expression and suggest a potential role for sirtuins in
      maintaining genome integrity. 

PMID- 25780932
TI  - The link between cardiovascular and circulatory events in inflammatory
      gastrointestinal disorders.

PMID- 25780931
TI  - Development and external validation of a prognostic nomogram for metastatic uveal
      melanoma.
AB  - BACKGROUND: Approximately 50% of patients with uveal melanoma (UM) will develop
      metastatic disease, usually involving the liver. The outcome of metastatic UM
      (mUM) is generally poor and no standard therapy has been established.
      Additionally, clinicians lack a validated prognostic tool to evaluate these
      patients. The aim of this work was to develop a reliable prognostic nomogram for
      clinicians. PATIENTS AND METHODS: Two cohorts of mUM patients, from Veneto
      Oncology Institute (IOV) (N=152) and Mayo Clinic (MC) (N=102), were analyzed to
      develop and externally validate, a prognostic nomogram. RESULTS: The median
      survival of mUM was 17.2 months in the IOV cohort and 19.7 in the MC cohort.
      Percentage of liver involvement (HR 1.6), elevated levels of serum LDH (HR 1.6),
      and a WHO performance status=1 (HR 1.5) or 2-3 (HR 4.6) were associated with
      worse prognosis. Longer disease-free interval from diagnosis of UM to that of mUM
      conferred a survival advantage (HR 0.9). The nomogram had a concordance
      probability of 0.75 (SE .006) in the development dataset (IOV), and 0.80 (SE
      .009) in the external validation (MC). Nomogram predictions were well calibrated.
      CONCLUSIONS: The nomogram, which includes percentage of liver involvement, LDH
      levels, WHO performance status and disease free-interval accurately predicts the
      prognosis of mUM and could be useful for decision-making and risk stratification
      for clinical trials.

PMID- 25780933
TI  - Porous Zr(x)Si(1-x)O2 shell/void/TiO2 core particles with enhancing transfer for
      cleaning water.
AB  - In order to immobilize TiO2 and prevent TiO2 nanoparticles from damaging
      polymeric supporters, the porous Zr(x)Si(1-x)O2 shell/void/TiO2 core particles
      (Zr-SVTs) were fabricated by the synergistic effect between nonionic surfactant
      P123 ((EO)20(PO)70(EO)20) and oleic acid (CH3(CH2)7CH=CH(CH2)7COOH) and
      cohydrolysis between TEOS and ZrOCl2.8H2O. Zr-SVTs were characterized by FT-IR,
      SEM, TEM, EDX and BET. The results show Zr-SVTs exhibit well-developed spherical
      shape with channels (approximately 5.5 nm in diameter) in porous Zr(x)Si(1-x)O2
      shells. Moreover, the preparation conditions of Zr-SVTs were studied and
      confirmed, and the photocatalytic activity of Zr-SVTs was studied by
      photodegrading methyl orange in aqueous solution and oil in sewage containing
      oil. Alternatively, the photocatalytic activity of Zr-SVTs presents better result
      compared with SiO2 shell/void/TiO2 core (SVT) without doping Zr into the SiO2
      shell, which further demonstrates that the Zr(x)Si(1-x)O2 shell could promote the
      mass transfer inside channels of Zr-SVTs. It suggests that Zr-SVTs with higher
      photocatalytic activity are desirable for application in water cleaning.

PMID- 25780934
TI  - Subclinical hypothyroidism might worsen the effects of aging on serum lipid
      profiles: a population-based case-control study.
AB  - BACKGROUND: Dyslipidemia is an important global health problem, particularly in
      the elderly population. Traditionally, the high prevalence of dyslipidemia in
      elderly people is considered a "natural condition." Notably, subclinical
      hypothyroidism (SCH) is one of the most important risk factors for dyslipidemia.
      Few studies have assessed whether SCH plays a role in the increase in age-related
      dyslipidemia. This study aimed to explore the association between SCH and lipid
      profiles in different age groups. METHODS: This was a large-scale, population
      based, case-control study. The population was derived from the REACTION study
      conducted across China. A total of 17,046 individuals (8827 cases and 8219
      controls) aged 40 years or older were enrolled in the final analyses. The
      relationships between SCH and serum lipid parameters in each age group were
      evaluated after adjustment for thyroid hormones and common confounding factors.
      RESULTS: In the entire population, thyrotropin (TSH), the key indicator of SCH,
      was positively associated with cholesterol parameters (total cholesterol [TC] and
      low-density lipoprotein cholesterol [LDL-C]) through the sixth decade of life.
      After adjusting for common confounding factors and thyroid hormones, each 1 mIU/L
      increase in TSH was estimated to elevate the TC level by 0.0147 mmol/L and 0.0551
      mmol/L, respectively, in individuals aged 40-49 years and 60-69 years. Similarly,
      with each 1 mIU/L increase in TSH, the LDL-C level tended to show gradually
      greater increases as age increased. In moderately old subjects (60-69 years),
      mild (TSH<=10 mIU/L) and significant (TSH>10 mIU/L) SCH increased the
      concentration of TC approximately 1.03- and 1.36-fold, and the concentration of
      LDL-C approximately 1.19- and 1.65-fold, respectively, when compared with younger
      subjects. CONCLUSIONS: TSH exhibited a stronger effect on the TC and LDL-C level
      in moderately old subjects than in younger subjects. SCH might augment and worsen
      the effects of aging on serum lipid profiles.

PMID- 25780935
TI  - A functional drug delivery platform for targeting and imaging cancer cells based
      on Pluronic F127.
AB  - Functional polymeric micelles play an important role in the efficient delivery of
      therapeutic drugs into tumours. In this study, a functional drug delivery
      platform with ligands for targeting and fluorescent imaging was designed based on
      Pluronic F127 (PF127). Using folic acid (FA) and fluorescein isothiocyanate
      (FITC) to chemically conjugate with PF127, two functional polymers, Pluronic F127
      FA (PF127-FA) and Pluronic F127-FITC (PF127-FITC), were synthesized. Solasodine
      loaded micelles were then prepared via the thin-film hydration method. By
      employing A549 and HeLa cells, the results of in vitro cell assays performed
      using confocal laser scanning microscopy and flow cytometry suggested that the
      proposed micelles could provide the desired specific targeting and fluorescent
      imaging functions. In addition, the results of in vitro cytotoxicity experiments
      showed that the growth inhibition rates of A549 and HeLa cells treated with
      solasodine-loaded micelles were remarkably higher than those of cells treated
      with free solasodine. Solasodine-loaded micelles exhibited a more distinct
      inhibitory effect against HeLa cells than against A549 cells. Thus, an effective
      drug delivery system for targeting and imaging cancer cells was developed. 

PMID- 25780936
TI  - Take-off time of the first generation of the overwintering small brown
      planthopper, Laodelphax striatellus in the temperate zone in East Asia.
AB  - Overseas migration of the small brown planthopper, Laodelphax striatellus
      (Fallen), occurs during the winter wheat harvest season in East Asia. Knowing the
      take-off time of emigrating L. striatellus is crucial for predicting such
      migrations with a simulation technique because winds, carriers of migratory
      insects, change continuously. Several methods were used in China and Japan from
      late May to early June 2012 and again in 2013 to identify the precise timing of
      take-off. These methods included: a tow net trap mounted to a pole at 10 m above
      the ground, a helicopter-towed net trap, and a canopy trap (which also had video
      monitoring) set over wheat plants. Laodelphax striatellus emigrated from wheat
      fields mainly in the early evening, before dusk. The insects also emigrated
      during the daytime but rarely emigrated at dawn, showing a pattern that is unlike
      the bimodal emigration at dusk and dawn of two other rice planthoppers, the brown
      planthopper, Nilaparvata lugens (Stal), and the white-backed planthopper,
      Sogatella furcifera (Horvath). There was no significant difference in the
      temporal pattern of take-off behavior between females and males of Japanese L.
      striatellus populations. 

PMID- 25780938
TI  - Single-layer graphene as a stable and transparent electrode for nonaqueous
      radical annihilation electrogenerated chemiluminescence.
AB  - We explored the use of single-layer graphene (SLG) obtained by chemical vapor
      deposition, and transferred to a glass substrate, as a transparent electrode
      material for use in coupled electrochemical and spectroscopic experiments in
      nonaqueous media through electrogenerated chemiluminescence (ECL). SLG was used
      with classical ECL luminophores, rubrene and 9,10-diphenylanthracene, in an inert
      environment to generate stable electrochemical responses and measure light
      emission through it. As an electrode material, SLG displayed excellent stability
      during electrochemical potential stepping and voltammetry in a window that
      spanned at least from ca. -2.4 to +1.8 V versus SCE in acetonitrile and
      acetonitrile/benzene. Although the peak splitting between forward and reverse
      sweeps in voltammetry was larger in comparison to metal electrodes due to in
      plane resistance, SLG displayed sufficiently facile electron transfer properties
      to yield stable voltammetric cycling and ECL. SLG electrodes patterned with poly
      tetrafluoroethylene permitted the stable generation of radical ions on an SLG
      microelectrode to be studied through scanning electrochemical microscopy in the
      generation/collection mode. SLG was able to stably collect radical ions produced
      by a 50 MUm gold tip with up to 96% collection efficiency. The transparency of
      graphene was used to obtain accurate spectral responses in ECL. While inner
      filter effects are known to cause a shift in peak emission wavelength of
      spectroelectrochemical studies, the use of SLG electrodes with detection through
      the graphene window reduced apparent peak shifts by up to 10 nm in peak
      wavelength. This work introduces SLG as a virtually transparent,
      electrochemically active, and chemically stable platform for studying ECL in the
      radical annihilation mode, where large electrode polarizations could compromise
      the chemical stability of other existing transparent electrodes. 

PMID- 25780937
TI  - Insulin receptor signaling in the GnRH neuron plays a role in the abnormal GnRH
      pulsatility of obese female mice.
AB  - Infertility associated with obesity is characterized by abnormal hormone release
      from reproductive tissues in the hypothalamus, pituitary, and ovary. These
      tissues maintain insulin sensitivity upon peripheral insulin resistance. Insulin
      receptor signaling may play a role in the dysregulation of gonadotropin-releasing
      hormone (GnRH) secretion in obesity, but the interdependence of hormone secretion
      in the reproductive axis and the multi-hormone and tissue dysfunction in obesity
      hinders investigations of putative contributing factors to the disrupted GnRH
      secretion. To determine the role of GnRH insulin receptor signaling in the
      dysregulation of GnRH secretion in obesity, we created murine models of diet
      induced obesity (DIO) with and without intact insulin signaling in the GnRH
      neuron. Obese control female mice were infertile with higher luteinizing hormone
      levels and higher GnRH pulse amplitude and total pulsatile secretion compared to
      lean control mice. In contrast, DIO mice with a GnRH specific knockout of insulin
      receptor had improved fertility, luteinizing hormone levels approaching lean
      mice, and GnRH pulse amplitude and total secretion similar to lean mice.
      Pituitary responsiveness was similar between genotypes. These results suggest
      that in the obese state, insulin receptor signaling in GnRH neurons increases
      GnRH pulsatile secretion and consequent LH secretion, contributing to
      reproductive dysfunction. 

PMID- 25780939
TI  - Effects of a partnership support program for couples undergoing fertility
      treatment.
AB  - AIM: The study's purpose was to examine the effects of providing a partnership
      support program. It was designed to improve Japanese couples' partnership,
      maintain quality of life, decrease psychological distress, and improve marital
      relationship satisfaction while they underwent infertility treatment that
      included the possibility of using assisted reproductive technology. METHODS: This
      quasi-experimental study with a two-group pretest-post-test design used purposive
      sampling and non-random assignment of 318 consenting Japanese patients from
      previous phases of assisted reproductive technology fertility treatment who were
      patients from a fertility clinic in Tokyo, Japan. The intervention group of 152
      patients (76 couples) participated in the partnership support program. The
      comparison group of 166 patients (83 couples) received usual care. Recruitment
      was age matched. The program provided information and used a participatory
      interactive approach to enhance understanding and cooperation in couples
      undergoing fertility treatment. The main outcome measures were: "partnership",
      FertiQoL, Quality Marriage Index, and "psychological distress". RESULTS: There
      were 311 participants (intervention group n = 148; comparison group, n = 163).
      The intervention group showed significant improvement in the couples'
      partnerships and a significant decrease in women's psychological distress using
      subgroup analysis. CONCLUSION: The partnership support program provided effective
      improvement in partnership for the couples, and reduced psychological distress
      for the women; however, it had less impact for the men. The program was not
      effective in improving couples' overall quality of life (QOL); however, it was
      effective in improving the "mind-body" aspects of the QOL subscale.

PMID- 25780940
TI  - Use of a new spirophosphine to achieve catalytic enantioselective [4 + 1]
      annulations of amines with allenes to generate dihydropyrroles.
AB  - Due in part to the common occurrence of five-membered nitrogen heterocycles in
      bioactive molecules, the discovery of methods for the enantioselective synthesis
      of such structures is a useful endeavor. Building on a single example by Tong of
      a phosphine-catalyzed [4 + 1] annulation of an amine with an allene that
      furnished an achiral dihydropyrrole in 22% yield, we have developed, with the aid
      of a new chiral spirophosphine catalyst, a method with increased utility,
      specifically, improved yield, enhanced scope (the use of gamma-substituted
      allenes), and good ee. The enantioenriched dihydropyrrole products can be
      transformed into other interesting families of compounds with very good
      stereoselectivity. 

PMID- 25780941
TI  - Hybrid halide perovskite solar cell precursors: colloidal chemistry and
      coordination engineering behind device processing for high efficiency.
AB  - The precursor of solution-processed perovskite thin films is one of the most
      central components for high-efficiency perovskite solar cells. We first present
      the crucial colloidal chemistry visualization of the perovskite precursor
      solution based on analytical spectra and reveal that perovskite precursor
      solutions for solar cells are generally colloidal dispersions in a mother
      solution, with a colloidal size up to the mesoscale, rather than real solutions.
      The colloid is made of a soft coordination complex in the form of a lead
      polyhalide framework between organic and inorganic components and can be
      structurally tuned by the coordination degree, thereby primarily determining the
      basic film coverage and morphology of deposited thin films. By utilizing
      coordination engineering, particularly through employing additional
      methylammonium halide over the stoichiometric ratio for tuning the coordination
      degree and mode in the initial colloidal solution, along with a thermal leaching
      for the selective release of excess methylammonium halides, we achieved full and
      even coverage, the preferential orientation, and high purity of planar perovskite
      thin films. We have also identified that excess organic component can reduce the
      colloidal size of and tune the morphology of the coordination framework in
      relation to final perovskite grains and partial chlorine substitution can
      accelerate the crystalline nucleation process of perovskite. This work
      demonstrates the important fundamental chemistry of perovskite precursors and
      provides genuine guidelines for accurately controlling the high quality of hybrid
      perovskite thin films without any impurity, thereby delivering efficient planar
      perovskite solar cells with a power conversion efficiency as high as 17% without
      distinct hysteresis owing to the high quality of perovskite thin films. 

PMID- 25780942
TI  - Prospective, Randomized Comparison of the Effect of Two Antimicrobial Regimes on
      Surgical Site Infection Rate in Dogs Undergoing Orthopedic Implant Surgery.
AB  - OBJECTIVES: To determine whether extending prophylactic antimicrobial
      administration into the postoperative period would decrease the surgical site
      infection (SSI) rate in clean canine orthopedic surgery associated with a metal
      implant. STUDY DESIGN: Randomized prospective clinical study. SAMPLE POPULATION:
      Consecutive procedures (n = 400) on dogs that had clean orthopedic surgery using
      a metal implant. METHODS: Cases were randomly allocated to 1 of 2 groups. Group 1
      was only administered perioperative antimicrobial drugs whereas group 2 was
      administered perioperative and 5 days of postoperative antimicrobial therapy.
      Owners were questioned or dogs were examined at 2 and 6 weeks after surgery to
      identify any SSI. Long term follow-up by questionnaire of the referring
      veterinary surgeon >=1 year after surgery was obtained. RESULTS: Ten of 191 dogs
      (5.24%) in group 1 developed SSI within 6 weeks compared with 7 of 198 (3.54%) in
      group 2; 7.22% of dogs in group 1 and 8.24% in group 2 developed infections more
      than 6 weeks after surgery. CONCLUSIONS: SSI rates in this population of dogs
      were similar where antimicrobial prophylaxis was administered perioperatively
      over 3 hours or as a course continued for 6 days.

PMID- 25780944
TI  - Evaluation of total mixed ration silage with brewers grains for dairy buffalo in
      Tarai, Nepal.
AB  - To investigate the effects of total mixed ration (TMR) silage, which contained
      brewers grain and rice straw as a substitute for conventional concentrate on feed
      intake and milk production in middle-to-late lactation buffaloes, four
      multiparous Murrah buffaloes were assigned to a 3 * 3 Latin square design
      experiment. The TMR silage, which had higher neutral and acid detergent fiber
      contents and digestibility than concentrate (P < 0.05) and similar crude protein
      (CP) and total digestible nutrient (TDN) contents with concentrate were used for
      the lactation experiment. The treatments were control (CTL) fed concentrate at
      0.6% of body weight (BW), and T1 and T2 fed the TMR silage at 0.6 and 1.2% of BW
      on a dry matter (DM) basis, respectively, with rice straw ad libitum. Daily
      intakes of DM, CP and TDN, and BW change were higher in T2 than in CTL and T1 (P
      < 0.05). Although milk composition did not differ among the treatments, milk
      yield (MY) was higher in T2 (P < 0.05). There were no significant differences in
      MY/DM intake and MY/TDN intake among the treatments. The increase of BW and MY in
      middle-to-late lactation buffaloes might have been due to high TDN intake from
      supplementary TMR silage.

PMID- 25780943
TI  - Tuberous sclerosis complex 2 loss increases lysophosphatidylcholine synthesis in
      lymphangioleiomyomatosis.
AB  - Lymphangioleiomyomatosis (LAM) is a destructive lung disease affecting women. LAM
      is caused by mutations in the tuberous sclerosis complex (TSC) genes. The TSC
      protein complex inhibits the mechanistic/mammalian target of rapamycin complex 1
      (mTORC1), which is a master regulator of cellular metabolism. Using mass
      spectrometry-based lipid profiling, we analyzed plasma from patients with LAM and
      discovered elevated levels of four lysophosphatidylcholine (LPC) species (C16:0,
      C18:0, C18:1, and C20:4) compared with those in healthy control women. To
      investigate whether these lipids are generated in a TSC2-dependent manner, we
      profiled in vitro preclinical models of TSC/LAM and found significant LPC
      accumulation in TSC2-deficient cells relative to TSC2-expressing control cells.
      These lysoglycerophospholipid changes occurred alongside changes in other
      phospholipid and neutral lipid species. Treatment with rapamycin or torin1 or
      down-regulation of sterol regulatory element-binding protein (SREBP), a lipogenic
      transcription factor, did not suppress LPC in TSC2-deficient cells. Inhibition of
      distinct isoforms of phospholipase A2 decreased the proliferation of TSC2
      deficient cells. Collectively, these results demonstrate that TSC2-deficient
      cells have enhanced choline phospholipid metabolism and reveal a novel function
      of the TSC proteins in choline lysoglycerophospholipid metabolism, with
      implications for disease pathogenesis and targeted therapeutic strategies. 

PMID- 25780945
TI  - Quantitation of selected terpenoids and mercaptans in the dual-purpose hop
      varieties Amarillo, Citra, Hallertau Blanc, Mosaic, and Sorachi Ace.
AB  - Free terpenoids and both free and bound polyfunctional thiols were investigated
      in five selected dual-purpose hop cultivars. Surprisingly, the dual-purpose
      Sorachi Ace variety was found to contain higher amounts of farnesene (2101 mg/kg)
      than aromatic hops such as Saaz but only traces of 3-methylbutylisobutyrate, a
      compound that usually distinguishes all bitter varieties. All five cultivars
      investigated here showed an exceptional citrus-like potential explained by either
      monoterpenic alcohols or polyfunctional thiols. Among the monoterpenic alcohols,
      beta-citronellol at concentrations above 7 mg/kg distinguished Amarillo, Citra,
      Hallertau Blanc, Mosaic, and Sorachi Ace from Nelson Sauvin and Tomahawk, two
      previously investigated dual-purpose hops, while linalool (312 mg/kg) and
      geraniol (211 mg/kg) remained good discriminating compounds for Nelson Sauvin and
      Tomahawk, respectively. Regarding polyfunctional thiols, higher amounts of 3
      sulfanylhexyl acetate (27 MUg/kg) characterized the Citra variety. Free 4
      sulfanyl-4-methylpentan-2-one proved discriminant for Sorachi Ace, while the
      bound form is predominant in Nelson Sauvin. On the other hand, an S-conjugate of
      3-sulfanylhexan-1-ol was found in Sorachi Ace at levels not far from those
      previously reported for Cascade, although the free form was undetected here. Both
      free and bound grapefruit-like 3-sulfanyl-4-methylpentan-1-ol (never evidenced
      before the present work) emerged as discriminating compounds for the Hallertau
      Blanc variety. The apotryptophanase assay also allowed us to evidence for the
      first time an S-conjugate of 2-sulfanylethan-1-ol. 

PMID- 25780946
TI  - Validity and reliability of a protocol of orofacial myofunctional evaluation for
      patients with obstructive sleep apnea.
AB  - There is no standardized protocol for the clinical evaluation of orofacial
      components and functions in patients with obstructive sleep apnea. The aim of
      this study was to examine the validity, reliability, and psychometric properties
      of the Expanded Protocol of Orofacial Myofunctional Evaluation with Scores (OMES
      expanded) in subjects with obstructive sleep apnea. Patients with obstructive
      sleep apnea and control subjects were evaluated, and the validity of OMES
      expanded was tested by construct validity (i.e. the ability to discriminate
      orofacial status between apneic and control subjects) and criterion validity
      (i.e. correlation between OMES-expanded and a reference instrument). Construct
      validity was adequate; the apneic group showed significantly worse orofacial
      status than did control subjects. Criterion validity of OMES-expanded was good,
      as was its reliability. The OMES-expanded is valid and reliable for evaluating
      orofacial myofunctional disorders of patients with obstructive sleep apnea, with
      adequate psychometric properties. It may be useful to plan a therapeutic strategy
      and to determine whether the effects of therapy are related to improved muscle
      and orofacial functions. 

PMID- 25780947
TI  - MS1-based label-free proteomics using a quadrupole orbitrap mass spectrometer.
AB  - Presented is a data set for benchmarking MS1-based label-free quantitative
      proteomics using a quadrupole orbitrap mass spectrometer. Escherichia coli digest
      was spiked into a HeLa digest in four different concentrations, simulating
      protein expression differences in a background of an unchanged complex proteome.
      The data set provides a unique opportunity to evaluate the proteomic platform
      (instrumentation and software) in its ability to perform MS1-intensity-based
      label-free quantification. We show that the presented combination of informatics
      and instrumentation produces high precision and quantification accuracy. The data
      were also used to compare different quantitative protein inference methods such
      as iBAQ and Hi-N. The data can also be used as a resource for development and
      optimization of proteomics informatics tools, thus the raw data have been
      deposited to ProteomeXchange with identifier PXD001385. 

PMID- 25780948
TI  - A molecular analysis of the patterns of genetic diversity in local chickens from
      western Algeria in comparison with commercial lines and wild jungle fowls.
AB  - The objectives of this study were to characterize the genetic variability of
      village chickens from three agro-ecological regions of western Algeria: coastal
      (CT), inland plains (IP) and highlands (HL), to reveal any underlying population
      structure, and to evaluate potential genetic introgression from commercial lines
      into local populations. A set of 233 chickens was genotyped with a panel of 23
      microsatellite markers. Geographical coordinates were individually recorded.
      Eight reference populations were included in the study to investigate potential
      gene flow: four highly selected commercial pure lines and four lines of French
      slow-growing chickens. Two populations of wild red jungle fowls were also
      genotyped to compare the range of diversity between domestic and wild fowls. A
      genetic diversity analysis was conducted both within and between populations.
      Multivariate redundancy analyses were performed to assess the relative influence
      of geographical location among Algerian ecotypes. The results showed a high
      genetic variability within the Algerian population, with 184 alleles and a mean
      number of 8.09 alleles per locus. The values of heterozygosity (He and Ho) ranged
      from 0.55 to 0.62 in Algerian ecotypes and were smaller than values found in
      Jungle fowl populations and higher than values found in commercial populations.
      Although the structuring analysis of genotypes did not reveal clear
      subpopulations within Algerian ecotypes, the supervised approach using
      geographical data showed a significant (p < 0.01) differentiation between the
      three ecotypes which was mainly due to altitude. Thus, the genetic diversity of
      Algerian ecotypes may be under the influence of two factors with contradictory
      effects: the geographical location and climatic conditions may induce some
      differentiation, whereas the high level of exchanges and gene flow may suppress
      it. Evidence of gene flow between commercial and Algerian local populations was
      observed, which may be due to unrecorded crossing with commercial chickens.
      Chicken ecotypes from western Algeria are characterized by a high genetic
      diversity and must be safeguarded as an important reservoir of genetic diversity.

PMID- 25780949
TI  - Gravitational erythema.
AB  - We report a case of gravitational erythema in a 13-year-old boy who presented
      with a blotchy erythematous rash affecting his arms when hanging down and legs
      and lower abdomen on standing. The cutaneous symptoms in the upper limbs would
      resolve rapidly on elevation of the arms, whereas the lower limb rash would
      disappear on lying flat. Although this is a benign condition, no effective
      treatment has previously been reported. Our patient was managed with compression
      stockings, which provided some symptomatic benefit. 

PMID- 25780950
TI  - Effects on bleeding complications of pharmacogenetic testing for initial dosing
      of vitamin K antagonists: a systematic review and meta-analysis: comment.

PMID- 25780951
TI  - A similarity-based QSAR model for predicting acute toxicity towards the fathead
      minnow (Pimephales promelas).
AB  - REACH regulation demands information about acute toxicity of chemicals towards
      fish and supports the use of QSAR models, provided compliance with OECD
      principles. Existing models present some drawbacks that may limit their
      regulatory application. In this study, a dataset of 908 chemicals was used to
      develop a QSAR model to predict the LC50 96 hours for the fathead minnow. Genetic
      algorithms combined with k nearest neighbour method were applied on the training
      set (726 chemicals) and resulted in a model based on six molecular descriptors.
      An automated assessment of the applicability domain (AD) was carried out by
      comparing the average distance of each molecule from the nearest neighbours with
      a fixed threshold. The model had good and balanced performance in internal and
      external validation (182 test molecules), at the expense of a percentage of
      molecules outside the AD. Principal Component Analysis showed apparent
      correlations between model descriptors and toxicity. 

PMID- 25780953
TI  - Selective catalytic reduction operation with heavy fuel oil: NOx, NH3, and
      particle emissions.
AB  - To meet stringent NOx emission limits, selective catalytic reduction (SCR) is
      increasingly utilized in ships, likely also in combination with low-priced higher
      sulfur level fuels. In this study, the performance of SCR was studied by
      utilizing NOx, NH3, and particle measurements. Urea decomposition was studied
      with ammonia and isocyanic acid measurements and was found to be more effective
      with heavy fuel oil (HFO) than with light fuel oil. This is suggested to be
      explained by the metals found in HFO contributing to metal oxide particles
      catalyzing the hydrolysis reaction prior to SCR. At the exhaust temperature of
      340  degrees C NOx reduction was 85-90%, while at lower temperatures the
      efficiency decreased. By increasing the catalyst loading, the low temperature
      behavior of the SCR was enhanced. The drawback of this, however, was the tendency
      of particle emissions (sulfate) to increase at higher temperatures with higher
      loaded catalysts. The particle size distribution results showed high amounts of
      nanoparticles (in 25-30 nm size), the formation of which SCR either increased or
      decreased. The findings of this work provide a better understanding of the usage
      of SCR in combination with a higher sulfur level fuel and also of ship particle
      emissions, which are a growing concern. 

PMID- 25780952
TI  - Diet soda intake is associated with long-term increases in waist circumference in
      a biethnic cohort of older adults: the San Antonio Longitudinal Study of Aging.
AB  - OBJECTIVES: To examine the relationship between diet soda (DS) intake (DSI) and
      long-term waist circumference (WC) change (DeltaWC) in the biethnic San Antonio
      Longitudinal Study of Aging (SALSA). DESIGN: Prospective cohort study. SETTING:
      San Antonio, Texas, neighborhoods. PARTICIPANTS: SALSA examined 749 Mexican
      American and European-American individuals aged 65 and older at baseline
      (baseline, 1992-96); 474 (79.1%) survivors completed follow-up 1 (FU1, 2000-01),
      413 (73.4%) completed FU2 (2001-03), and 375 (71.0%) completed FU3 (2003-04).
      Participants completed a mean of 2.64 follow-up intervals, for 9.4 total follow
      up years. MEASUREMENTS: DSI, WC, height, and weight were measured at outset and
      at the conclusion of each interval: baseline, FU1, FU2, and FU3. RESULTS:
      Adjusted for initial WC, demographic characteristics, physical activity, diabetes
      mellitus, and smoking, mean interval DeltaWC of DS users (2.11 cm, 95% confidence
      interval (CI) = 1.45-2.76 cm) was almost triple that of nonusers (0.77 cm, 95% CI
      = 0.29-1.23 cm) (P < .001). Adjusted interval DeltaWCs were 0.77 cm (95% CI =
      0.29-1.23 cm) for nonusers, 1.76 cm (95% CI = 0.96-2.57 cm) for occasional users,
      and 3.04 cm (95% CI = 1.82-4.26 cm) for daily users (P = .002 for trend). This
      translates to DeltaWCs of 0.80 inches for nonusers, 1.83 inches for occasional
      users, and 3.16 for daily users over the total SALSA follow-up. In subanalyses
      stratified for selected covariates, DeltaWC point estimates were consistently
      higher in DS users. CONCLUSION: In a striking dose-response relationship,
      increasing DSI was associated with escalating abdominal obesity, a potential
      pathway for cardiometabolic risk in this aging population.

PMID- 25780954
TI  - Second versus first generation DES in multiple vessel disease and unprotected
      left main stenosis: insights from ERACI IV Study.
AB  - Recent data from randomized clinical trials (RCT) between PCI with first
      generation drug-eluting stent (DES) versus coronary artery bypass graft (CABG)
      showed a lack of benefit in the incidence of death and myocardial infarction (MI)
      with PCI. However in the last years a large improvement in the DES platforms was
      seen and was translated to a significant increase in safety and efficacy observed
      in RCT and observational studies. However, at present time little is known about
      the role of second generation DES in patients with complex multiple vessel
      coronary artery disease (CAD). ERACI IV registry is a multicenter, prospective
      and controlled open label study that evaluates a second generation DES, for the
      treatment of patients with multiple vessel CAD including unprotected left main.
      End point was to compare major adverse cardiovascular events (MACCE) and each
      component of them with previous arms of ERACI III study, first generation DES and
      CABG. ERACI IV compared to ERACI III DES arm, had greater number of diabetics (p
      = 0.02), at rest unstable angina (P = 0.01), 3 vessels plus left main (P = 0.02)
      and also more stent length per patient (P = 0.03).In ERACI IV 66.2% of patients
      had intermediate or high Syntax score. At one year, patients treated with 2nd
      generation compared to 1st generation DES had lower incidence of death (0.4% vs.
      3.1% 4 P = 0.03), death/MI/stroke (0.9 vs. 6.7% P = 0.001), unplanned
      revascularization (1.8% vs. 8.9%, P = 0.001) and MACCE (2.2% vs. 12% P <= 0.001).
      Advantages was also observed in diabetics, MI (0% vs. 8.5 P = 0.05),
      death/MI/stroke (0% vs. 12.8%, P = 0.009), unplanned revascularization (1.4% vs.
      14.9%, P = 0.01) and MACCE (1.4% vs. 21.3%, P < 0.001). In ERACI IV diabetic and
      non-diabetics had similar MACCE (1.4% vs. 2.6 %, P = 0.97). In conclusion, at one
      year follow-up patients treated with second generation DES showed a remarkable
      low incidence of MACCE and any component of them; benefit was also seen in
      diabetics.

PMID- 25780955
TI  - Rules and stereoelectronic guidelines for the anionic nucleophilic displacement
      of furanoside and furanose O-sulfonates.
AB  - Rules for predicting anionic SN2 displacement viability in furanose and
      furanoside sulfonates are presented. 

PMID- 25780956
TI  - Automatic seizure detection using Stockwell transform and boosting algorithm for
      long-term EEG.
AB  - Automatic detection of seizures has vital significance for epileptic diagnosis
      and can efficiently reduce the workload of the medical staff. In this study, a
      novel seizure detection method based on Stockwell transform is proposed for
      intracranial long-term EEG data. The Stockwell transform is employed to obtain
      the time-frequency representation of the EEG signals, and then the power spectral
      density is calculated in the time-frequency plane to characterize the behavior of
      EEG recordings. After that, a classifier based on gradient boosting algorithm is
      used to make the classification. Finally, the postprocessing is utilized on the
      outputs of the classifier to obtain more stable and accurate detection results,
      which includes Kalman filter, threshold judgment, and collar technique. The
      performance of this method is assessed on the publicly available EEG database
      which contains approximately 533h of intracranial EEG recordings. The
      experimental results indicate that the proposed method can achieve a satisfactory
      sensitivity of 94.26%, a specificity of 96.34%, as well as a very short delay
      time of 0.56s. 

PMID- 25780957
TI  - Combined Effects of Drop Height and Fatigue on Landing Mechanics in Active
      Females.
AB  - Drop height and fatigue have been shown in isolation to affect landing mechanics
      and increase the risk of sustaining an anterior cruciate ligament injury. The
      purpose of this study was to identify the combined effects of drop height and
      fatigue on landing mechanics in recreationally active females. To assess this, 11
      healthy, young adult females performed a series of drop jumps from randomized
      heights before and following a lower extremity fatiguing protocol. Findings for
      kinematic results demonstrated that hip flexion decreased at initial contact (P =
      .003) and maximum hip (P = .005) and knee flexion (P = .001) angles increased
      with increases in drop height. Kinetic results demonstrated that vertical ground
      reaction forces and joint moments and powers increased as height increased.
      Ground reaction forces and maximum knee valgus increased from pre- to postfatigue
      with interactive effects observed in frontal plane hip angle at impact and peak
      ankle moment. These results confirm the effects of drop height and fatigue and
      highlighted interactions between these factors. The differential effect of
      fatigue as a function of drop heights helps to illustrate potentially risky
      situations that should be addressed in training and injury prevention programs. 

PMID- 25780958
TI  - Coupled phases and combinatorial selection in fluctuating hydrothermal pools: a
      scenario to guide experimental approaches to the origin of cellular life.
AB  - Hydrothermal fields on the prebiotic Earth are candidate environments for
      biogenesis. We propose a model in which molecular systems driven by cycles of
      hydration and dehydration in such sites undergo chemical evolution in dehydrated
      films on mineral surfaces followed by encapsulation and combinatorial selection
      in a hydrated bulk phase. The dehydrated phase can consist of concentrated
      eutectic mixtures or multilamellar liquid crystalline matrices. Both conditions
      organize and concentrate potential monomers and thereby promote polymerization
      reactions that are driven by reduced water activity in the dehydrated phase. In
      the case of multilamellar lipid matrices, polymers that have been synthesized are
      captured in lipid vesicles upon rehydration to produce a variety of molecular
      systems. Each vesicle represents a protocell, an "experiment" in a natural
      version of combinatorial chemistry. Two kinds of selective processes can then
      occur. The first is a physical process in which relatively stable molecular
      systems will be preferentially selected. The second is a chemical process in
      which rare combinations of encapsulated polymers form systems capable of
      capturing energy and nutrients to undergo growth by catalyzed polymerization.
      Given continued cycling over extended time spans, such combinatorial processes
      will give rise to molecular systems having the fundamental properties of life. 

PMID- 25780959
TI  - Nitrogen Starvation Acclimation in Synechococcus elongatus: Redox-Control and the
      Role of Nitrate Reduction as an Electron Sink.
AB  - Nitrogen starvation acclimation in non-diazotrophic cyanobacteria is
      characterized by a process termed chlorosis, where the light harvesting pigments
      are degraded and the cells gradually tune down photosynthetic and metabolic
      activities. The chlorosis response is governed by a complex and poorly understood
      regulatory network, which converges at the expression of the nblA gene, the
      triggering factor for phycobiliprotein degradation. This study established a
      method that allows uncoupling metabolic and redox-signals involved in nitrogen
      starvation acclimation. Inhibition of glutamine synthetase (GS) by a precise
      dosage of l-methionine-sulfoximine (MSX) mimics the metabolic situation of
      nitrogen starvation. Addition of nitrate to such MSX-inhibited cells eliminates
      the associated redox-stress by enabling electron flow towards nitrate/nitrite
      reduction and thereby, prevents the induction of nblA expression and the
      associated chlorosis response. This study demonstrates that nitrogen starvation
      is perceived not only through metabolic signals, but requires a redox signal
      indicating over-reduction of PSI-reduced electron acceptors. It further
      establishes a cryptic role of nitrate/nitrite reductases as electron sinks to
      balance conditions of over-reduction. 

PMID- 25780961
TI  - Successful use of the excimer laser for generalized psoriasis in an ustekinumab
      non-responder.
AB  - Effective treatments for moderate to severe psoriasis are phototherapy and
      biologics. These treatments are similar in that they both decrease cutaneous
      immune system hyperactivity yet do so via different mechanisms. Our patient, a 63
      year old Asian male had a rapid response to treatment with the high dose excimer
      laser, having previously failed treatment with 28 weeks of ustekinumab therapy. A
      pre-treatment biopsy of a psoriatic plaque was found to contain relatively low
      levels of IFN-gamma (Th1) and IL-17 (Th17) secreting T cells. Following treatment
      with the excimer laser, the patient had a quick improvement in PASI that was
      reflected by a 3-fold reduction in the number of live T cells found in the post
      treatment biopsy. Although ustekinumab and the excimer laser both result in
      decreased levels of these cytokines, the excimer laser directly causes apoptosis
      of T cells and induces DNA damage in antigen presenting cells. Thus, the broader
      effects of phototherapy on immune cells compared to the targeted inhibition of IL
      12 and IL-23 by ustekinumab likely account for the superior response observed.

PMID- 25780960
TI  - The Expansion of Animal MicroRNA Families Revisited.
AB  - MicroRNAs are important regulatory small RNAs in many eukaryotes. Due to their
      small size and simple structure, they are readily innovated de novo. Throughout
      the evolution of animals, the emergence of novel microRNA families traces key
      morphological innovations. Here, we use a computational approach based on
      homology search and parsimony-based presence/absence analysis to draw a
      comprehensive picture of microRNA evolution in 159 animal species. We confirm
      previous observations regarding bursts of innovations accompanying the three
      rounds of genome duplications in vertebrate evolution and in the early evolution
      of placental mammals. With a much better resolution for the invertebrate lineage
      compared to large-scale studies, we observe additional bursts of innovation,
      e.g., in Rhabditoidea. More importantly, we see clear evidence that loss of
      microRNA families is not an uncommon phenomenon. The Enoplea may serve as a
      second dramatic example beyond the tunicates. The large-scale analysis presented
      here also highlights several generic technical issues in the analysis of very
      large gene families that will require further research. 

PMID- 25780962
TI  - Scleromyxedema with histology resembling granuloma annulare.
AB  - Scleromyxedema is a generalized and progressive fibromucinous disorder associated
      with substantial cutaneous and systemic morbidity. The diagnosis is often
      challenging, as is management. We present here a patient with scleromyxedema with
      atypical, granuloma annulare-like histology, which contributed to delayed
      diagnosis and management, including a delayed workup for multiple myeloma.
      Ultimately, the patient did well with appropriate therapy, but his presentation
      illustrates the importance of more widespread familiarity among dermatologists
      and dermatopathologists with this variant of scleromyxedema. 

PMID- 25780963
TI  - Marginal vitiligo: an unusual depigmenting disorder.
AB  - BACKGROUND: Marginal vitiligo, or inflammatory vitiligo with raised borders is a
      unique subset of vitiligo vulgaris presenting with scattered depigmented,
      pruritic patches surrounded by a raised, erythematous border. Alternative
      diagnoses include discoid lupus erythematosus and cutaneous T-cell lymphoma.
      PURPOSE: To properly guide treatment, it is important to exclude other conditions
      that present with a similar pattern of depigmentation. This requires the ability
      to identify specific cutaneous and histologic clues that support this diagnosis.
      MATERIAL AND METHODS: A 22 year-old man presented with a history of depigmented,
      pruritic patches and surrounding raised, erythematous borders. Several areas of
      depigmentation on the scalp were associated with alopecia. Punch biopsy of the
      rim of a patch was performed and sent for routine hematoxylin and eosin staining
      and direct immunofluorescence. RESULTS AND CONCLUSION: Histopathology revealed a
      spongiotic dermatitis with superficial dermal lymphocytic infiltrate and
      eosinophils; DIF demonstrated no immunoreactants. A diagnosis of inflammatory
      vitiligo with raised borders was thus made based on consistent clinical and
      histopathologic features. The symptoms improved with topical clobetasol 0.05%
      cream twice daily.

PMID- 25780964
TI  - Infantile perianal protrusion.
AB  - Infantile perianal protrusion is characterized by a skin fold located in the
      perianal area. It is a relatively recent reported condition and affects both
      infants and prepubertal children with a clear female predominance. Three types
      are recognized: constitutional/congenital, acquired, and associated with lichen
      sclerosus et atrophicus. We report eleven new cases, three of whom have the
      defect in locations that have been reported only once before. We would like to
      increase the awareness of this condition to avoid erroneous diagnostic and
      therapeutic procedures. 

PMID- 25780965
TI  - Reed syndrome: an atypical presentation of a rare disease.
AB  - Reed syndrome, also known as Multiple Uterine and Cutaneous Leiomyomas (MCUL), is
      an autosomal dominant defect in the fumurate hydrase gene, leading to a
      predisposition of leiomyomas of the skin and uterus. Patients with Reed syndrome
      may present with cutaneous leiomyomas, uterine leiomyomas and/or leiomyosarcomas.
      A 37-year-old woman presented to the dermatology clinic with several subcutaneous
      nodules. Punch biopsy was performed and the diagnosis of angioleiomyosarcoma with
      supervening degenerative changes was made. Medical history was positive for
      uterine leiomyomas. These concomitant findings led to the diagnosis of Reed
      syndrome. At the present time, genetic counseling is a suggested screening
      parameter for patients with multiple cutaneous leiomyomas. The superficial nature
      of these lesions and the low staging made surgical excision the preferred and
      actual treatment method. Adjunct radiation and chemotherapy have not been shown
      to provide clear benefit of survival. Owing to an association with renal cell
      carcinoma, a referral for nephrology consultation is also recommended. 

PMID- 25780966
TI  - Lues maligna praecox: an important consideration in HIV-positive patients with
      ulceronodular skin lesions.
AB  - Syphilis is commonly known as "the great imitator" owing to its varied clinical
      manifestations. Secondary syphilis has a variety of presentations, with the most
      common manifesting as a diffuse papulosquamous eruption on the palms and soles.
      Lues maligna praecox is a rare form of secondary syphilis, with severe
      constitutional symptoms, seen primarily in HIV-positive individuals. We report an
      atypical case of suspected lues maligna in a 45-year-old male. The patient was
      HIV-positive with a CD4 count of 441. He presented to our clinic with large
      painful gummatous ulcers in the groin and lower back. He also reported daily
      fevers, night sweats, and weight loss consistent with secondary syphilis. Prior
      to this episode the patient had a history of acute active syphilis (RPR 1:128) in
      2012 treated at that time with a single dose of 2.4 million units intramuscular
      benzathine penicillin; he had no reported exposures since that time. The patient
      was treated with three weekly doses of benzathine penicillin, 2.4 million units,
      given intramuscularly. This case demonstrates the importance of recognizing the
      varied clinical presentation of secondary syphilis and keeping lues maligna in
      consideration for ulceronodular skin lesions in patients who are HIV-positive.

PMID- 25780967
TI  - [Cutaneous and subcutaneous leiomyosarcoma: report of two cases].
AB  - Cutaneous leiomyosarcomas are uncommon malignant tumors of smooth muscle. We
      report herein two cases of cutaneous leiomyosarcoma, one of dermal and other of
      subcutaneous vascular origin, confirmed by histology and immunohistochemistry.
      Both cases were treated with wide surgical excision, one with local recurrence.
      No metastases were detected at follow-up. Leiomyosarcomas should be considered in
      lesions with histologic features of spindle cell malignancy. It is necessary in
      most of the cases a histological differentiation with specific
      immunohistochemical markers. The treatment of choice is radical excision with
      wide margins, achieving satisfactory results. 

PMID- 25780968
TI  - A case of generalized red sweating.
AB  - We report a case of a 70-year-old man with a 5-year history of red pigmented
      sweating on the axillae, groin, forearms, trunk, and and peri-nuchal sites. No
      identifiable cause of the pigmented sweat was identified. Biopsy revealed
      lipofuscin pigment leading to the diagnosis of idiopathic chromhidrosis. This
      case represents an unusual presentation of chromhidrosis that was not limited to
      the apocrine sweat gland distribution and ultimately revealed no identifiable
      cause. After failing multiple treatment options, the patient elected for a trial
      of treatment with 20% aluminum chloride solution. 

PMID- 25780969
TI  - Eccrine chromhidrosis secondary to hyperbilirubinemia.
AB  - BACKGROUND: Eccrine chromhidrosis, or colored eccrine sweating, may be caused by
      contamination of sweat by dyes, pigmentation from microorganisms, or more rarely,
      hyperbilirubinemia. Pigment usually affects the palms and soles, where abundant
      sweat glands are found.Purpose, Material and Methods: We report a unique case of
      eccrine chromhidrosis in the setting of hyperbilirubinemia and review the current
      literature available on PubMed of previously reported cases. RESULTS: Six
      patients with chromhidrosis have been previously reported in the setting of
      significant hyperbilirubinemia, in association with fever and thickened stratum
      corneum. CONCLUSIONS: Eccrine chromhidrosis secondary to hyperbilirubinemia is
      very rare, but can be diagnosed on the basis of classic clinical findings,
      dermoscopic examination, and negative tissue cultures.

PMID- 25780970
TI  - Primary mucocutaneous histoplasmosis in an immunocompetent patient.
AB  - We report a case of primary mucocutaneous histoplasmosis in an immunocompetent
      individual. The patient, a 61-year-old woman, presented with a non-healing ulcer
      on the lateral border of her tongue. Excisional biopsy of the lesion was
      consistent with histoplasmosis and no evidence of pulmonary or disseminated
      infection was found. Although mucocutaneous infection has been well-described as
      a manifestation of disseminated disease, especially in immunocompromised
      individuals, oral infections in immunocompetent patients are rare.

PMID- 25780971
TI  - Cutaneous metastasis from penile squamous cell carcinoma resembling carcinoma en
      cuirasse.
AB  - Penile squamous cell carcinoma is a rare malignancy seen more frequently in
      developing nations. Metastasis occurs in a predictable manner, with superficial
      lymph node involvement occurring first, followed by deep lymph node involvement,
      and then distant spread. Brain, lung, liver, and bone are the typical sites of
      distant metastasis. We present the unusual case of an 81-year-old man with penile
      squamous cell carcinoma requiring total penectomy who developed a confluent red
      to violaceous, indurated suprapubic plaque with satellite papules and bulky
      inguinal lymphadenopathy. The shield-like clinical presentation and infiltrating
      strands and cords on histology resembled carcinoma en cuirasse, a rare form of
      cutaneous metastasis frequently associated with breast cancer but not reported
      with penile squamous cell carcinoma.

PMID- 25780972
TI  - Varicella zoster virus encephalitis in a patient with disseminated herpes zoster:
      report and review of the literature.
AB  - Herpes zoster infection occurs owing to reactivation of varicella zoster virus
      and classically manifests as a vesicular eruption involving a single dermatome.
      Disseminated herpes zoster - defined as having greater than twenty vesicles
      outside the primary or adjacent dermatome - is uncommon and typically occurs in
      immunocompromised individuals. Central nervous system complications during or
      following a zoster outbreak are exceedingly rare. Encephalitis is reported to
      affect only 0.1-0.2% of patients and occurs more often in disseminated cases and
      in outbreaks involving those dermatomes in close proximity to the central nervous
      system. We present an elderly woman with disseminated herpes zoster and altered
      mental status who was subsequently diagnosed with varicella zoster virus
      encephalitis and describe the characteristics of patients with disseminated
      zoster who developed varicella zoster virus encephalitis. 

PMID- 25780973
TI  - Pemphigus vulgaris presenting with multiple lesion morphologies.
AB  - Pemphigus vulgaris is an uncommon intraepidermal blistering disorder that
      typically presents with flaccid bullae or erosions. We report a patient with
      pemphigus vulgaris who presented with several unusual clinical features: tense
      bullae with dependently layered pus, true target lesions coalescing into annular
      configurations, and diffuse desquamation that initially raised concern for toxic
      epidermal necrolysis. We discuss the differential diagnosis and implications of
      these morphological findings. 

PMID- 25780974
TI  - Blastic plasmacytoid dendritic cell neoplasm of the skin associated with
      myelodysplastic syndrome.
AB  - Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a recently described,
      rare hematologic malignancy with prominent skin involvement. The prognosis of
      this disease is poor in most cases, with rapid progression despite chemotherapy
      administration. The first reported case of this disease was in 1994, and less
      than 200 cases worldwide have been described in the literature to date. Moreover
      coexistence of BPDCN and MDS is extremely rare. In this study, we describe a
      typical patient with BPDCN in China who presented with cutaneous involvement as
      the first manifestation associated with MDS; a brief review of literature is also
      given.

PMID- 25780975
TI  - Lipoid Proteinosis: a case report in two siblings.
AB  - Lipoid proteinosis was first reported by Urbach and Wiethe in 1929. It is also
      known as hyalinosis cutis et mucosae or Urbach-Wiethe disease. It is a rare
      autosomal recessive disorder and characterized by the infiltration of hyaline
      material in the skin, oral cavity, larynx, and internal organs. Lipid proteinosis
      presents early in life. Hoarseness develops in infancy. The classic sign is
      beaded eyelid papules along the lid margin, also known as 'Monilform
      Blepherosis'. In India about 30 cases have been reported to date. We report the
      following case because of its rarity in the Indian literature. 

PMID- 25780976
TI  - Otophyma: a rare benign clinical entity mimicking leprosy.
AB  - Otophyma is a rare condition characterized by edematous deformation of the ear
      that is considered to be the end-stage of an inflammatory process such as rosacea
      and eczema. This report illustrates a case in an elderly male, originally thought
      to have leprosy. Biopsy revealed a nodular infiltration of inflammatory cells
      around adnexal structures and an intraepidermal cyst. No acid-fast organisms were
      identified. We present a patient who is of a different ethnic group than usually
      seen with this disease and provide a review of the clinical presentation,
      histopathological features, and management of this rare condition. 

PMID- 25780978
TI  - Maintenance of certification and the financial status of the medical boards.
AB  - BACKGROUND: The Maintenance of Certification (MOC) program proposed by the
      American Board of Medical Specialties (ABMS) gained approval in 2006. The
      implementation of this program will impact all physicians who are board
      certified. Therefore, The Financial Status of the Medical Boards is an
      increasingly relevant topic of discussion amongst all physicians and those
      interested in medical education and certification. With this study we aim to
      bring greater attention to the already publicly available financial status of the
      Medical Boards (MB) so that it can become part of the ongoing discussion of MOC.
      METHOD: We analyzed the yearly revenue, expenses, net gain or loss and end of
      year balance for the ABMS and its 24 MB, additional member boards, as well as the
      Accreditation Council for Graduate Medical Education (ACGME), American
      Osteopathic Association (AOA) and Accreditation Council for Continuing Medical
      Education (ACCME) organizations. RESULTS: We have commented on notable trends
      based on the available IRS Form 990s spanning from 1997 to 2012. When comparing
      the most recently available reported end of year balance to the first available
      reported end of year balance, 87% (27/31) of the member boards have reported an
      increase. All three of the additional organizations studied, ACGME, AOA and ACCME
      reported an increase as well. CONCLUSIONS: It is clear from the data and analysis
      that the majority of MB have financially benefited from the MOC program. It
      remains to be proven whether or not this economic benefit will translate into an
      improvement in physician education and patient care.

PMID- 25780977
TI  - Extensive cutaneous sarcoidosis and coexistant Crohn disease with dual response
      to infliximab: case report and review of the literature.
AB  - Sarcoidosis and Crohn disease (CD) are granulomatous disorders of unknown
      etiology that are rarely seen together in one patient. We describe a woman in her
      40s with well-established diagnoses of pulmonary and cutaneous sarcoidosis and CD
      involving the terminal ileum, whose skin and gastrointestinal symptoms improved
      dramatically with infliximab treatment (5mg/kg on weeks 0, 2, 6, then every 8
      weeks). The concurrence of sarcoidosis and CD has only been reported in a handful
      of cases and a review of the literature reveals that the two diseases share many
      clinical and immunological features, suggesting the presence of an underlying
      connection. Further studies of patients with overlap syndromes may provide deeper
      insight into the clinical spectrum, and possibly the pathogenesis, of idiopathic
      granulomatous diseases. 

PMID- 25780979
TI  - Histiocytoid giant cellulitis-like Sweet's syndrome: case report and review of
      the literature.
AB  - BACKGROUND: Histiocytoid Sweet syndrome is an uncommon variant in which the
      dermal infiltrate is composed of mononuclear cells with a histiocytic appearance
      that represent immature myeloid cells. Giant cellulitis-like Sweet syndrome is a
      recently described variant characterized by relapsing widespread giant lesions.
      PURPOSE: We report a unique patient with histiocytoid giant cellulitis-like Sweet
      syndrome and review the current literature on histiocytoid Sweet syndrome and
      giant cellulitis-like Sweet syndrome. MATERIAL AND METHODS: We reviewed PubMed
      for the following terms and have reviewed the literature: histiocytoid, giant
      cellulitis-like, and Sweet syndrome. RESULTS: Six individuals, including our
      patient, have been reported with giant cellulitis-like Sweet syndrome; four had
      obesity, two had a hematologic malignancy, and one had breast cancer.
      Histiocytoid Sweet syndrome has been reported in association with autoimmune
      diseases, infection or inflammation, inflammatory bowel disease, malignancies,
      medications, and other conditions. CONCLUSIONS: Histiocytoid Sweet syndrome is a
      rare variant of Sweet syndrome, often associated with malignancy. Giant
      cellulitis-like Sweet syndrome has been reported in six individuals; four of the
      patients were obese and three of the patients had an associated cancer. Our
      patient had histiocytoid giant cellulitis-like Sweet syndrome-associated
      myelodysplastic syndrome/myeloproliferative disorder. The diagnosis of
      histiocytoid Sweet syndrome or giant cellulitis-like Sweet syndrome should prompt
      the clinician to consider additional evaluation for a Sweet syndrome-associated
      malignancy.

PMID- 25780980
TI  - Disseminated varicella-zoster virus in an immunocompetent adult.
AB  - Varicella-zoster is the virus that causes varicella (chicken pox), herpes zoster
      (shingles), and rarely, severe disseminated disease including diffuse rash,
      encephalitis, hepatitis, and pneumonitis. Disseminated disease is most often seen
      in immunocompromised patients. We describe a case of disseminated zoster in an
      immunocompentent patient who had previously been immune to VZV. This case is also
      unusual in that his clinical presentation was most consistent with varicella
      while his laboratory data was most consistent with herpes zoster. For the purpose
      of rapid diagnosis and initiation of appropriate therapy, clinicians should be
      aware of these more atypical presentations of VZV infection. 

PMID- 25780981
TI  - Elejalde syndrome (ES).
AB  - Silvery hair and severe dysfunction of the central nervous system
      (Neuroectodermal melanolysosomal disease or Elejalde Syndrome) characterize this
      rare autosomal recessive syndrome. The main clinical features include silver
      leaden hair, bronze skin after sun exposure, and neurologic involvement. Large
      granules of melanin unevenly distributed in the hair shaft are observed. Abnormal
      melanocytes and melanosomes and abnormal inclusion bodies in fibroblasts may be
      present. We report a 10-year-old girl with silver-leaden (silvery) hair, bronze
      skin color on sun-exposed areas, generalized hypopigmentation of covered body
      parts, and congenital seizures. The child was the elder of two children born of a
      consanguineous marriage. The younger sibling, a female neonate, had the same
      clinical presentation. 

PMID- 25780982
TI  - Cutaneous manifestations of the Ebola virus.
AB  - The current Ebola outbreak has drawn attention to the virus in the medical
      community. Zaire ebolavirus, more commonly known as 'the Ebola virus,' is a level
      4-security agent in the Filoviridae family. The main cutaneous finding of Ebola
      is a nonspecific maculopapular rash that appears between day four and six of
      disease. Patients have "ghost-like" features, and the rash initially presents on
      the upper arms, flexor forearms, and upper legs, sometimes in a centripetal
      fashion. Skin biopsy, immunohistochemistry, ELISA, and electron microscopy can
      help provide early diagnosis and conceivably prevent spread if proper
      precautionary measures are in place. 

PMID- 25780983
TI  - Dermatitis medicamentosa: severe rebound erythema secondary to topical
      brimonidine in rosacea.
AB  - BACKGROUND: Rebound erythema secondary to use of topical brimonidine in the
      setting of rosacea is an important, possibly significantly distressing potential
      side effect that may be under-reported; there is little photo-documentation in
      the literature to date. This article documents such a case. OBSERVATIONS: A 28
      year-old woman (Fitzpatrick II) with a long-standing history of untreated rosacea
      presented for initiation of treatment of what was noted to be primarily
      erythematotelangiectatic rosacea and was offered Mirvaso for daily use. Initial
      improvement was followed by progressive worsening of baseline erythema several
      hours following treatment, only improved with subsequent applications of
      additional Mirvaso. The patient's symptoms were improved upon discontinuing use
      of Mirvaso. CONCLUSIONS: There are few cases documented of rebound erythema
      secondary to use of Mirvaso to date. Further reporting might prompt further long
      term investigation for this topical medication for further delineation of its
      role in treatment of rosacea. What is proposed is a phenomenon similar to that of
      rhinitis medicamentosa with upregulation of alph-adrenergic receptors, suggesting
      the name "dermatitis medicamentosa" for this phenomenon.

PMID- 25780984
TI  - [NiFe]-hydrogenases revisited: nickel-carboxamido bond formation in a variant
      with accrued O2-tolerance and a tentative re-interpretation of Ni-SI states.
AB  - [NiFe]-hydrogenases are well-studied enzymes capable of oxidizing molecular
      hydrogen and reducing protons. EPR and FTIR spectroscopic studies have shown that
      these enzymes can be isolated in several redox states that include paramagnetic
      oxidized inactive Ni-A and Ni-B species and a reduced Ni-C form. The latter and
      the diamagnetic respectively more oxidized Ni-SI and more reduced Ni-R forms are
      generally thought to be involved in the catalytic cycle of [NiFe]-hydrogenases.
      With the exception of Ni-SI, these different stable states have been well
      characterized. Here, based on the crystal structure of a partially reduced
      Desulfovibrio fructosovorans (Df) enzyme and data from the literature we propose
      that at least one of the Ni-SI sub-states contains an unexpected combination of
      hydride and sulfenic acid moieties. We have also determined the structure of the
      less oxygen-sensitive Df [NiFe]-hydrogenase V74C mutant and found that more than
      half of the active site nickel occupies a novel position, called Ni'. In this new
      position, the metal ion is coordinated by two cysteine thiolates, a bridging
      species modeled as SH(-) and a main chain carboxamido N atom. The Ni'
      coordination is similar to the one found in Ni superoxide dismutase, an enzyme
      that operates at significantly more positive potentials than [NiFe]-hydrogenases.
      We propose that the oxygen-tolerance of the V74C variant results from a high
      potential stabilization of a Ni'(iii) species induced by the change in the metal
      ion coordination sphere. We also propose that transient Ni'(iii) species can
      rapidly attract successive electrons from the Fe4S4 proximal cluster accelerating
      the reduction of oxygen to water and hydroxide. The naturally occurring oxygen
      tolerant [NiFe]-hydrogenases have an unusual proximal cluster that has been shown
      to be exceptionally plastic and capable of undergoing two successive one-electron
      oxidations. This double oxidation is modulated by the migration of one of the
      iron atoms in the cluster to the main chain where, as Fe(iii), it forms a bond
      with a carboxamido N ligand. Like in the Df V74C variant the electrons from the
      proximal cluster help reducing O2 to H2O and OH(-). In conclusion, in both cases
      a metal-carboxamido bond may explain, at least partially, the observed oxygen
      tolerance. 

PMID- 25780985
TI  - Combinatorial Libraries As a Tool for the Discovery of Novel, Broad-Spectrum
      Antibacterial Agents Targeting the ESKAPE Pathogens.
AB  - Mixture based synthetic combinatorial libraries offer a tremendous enhancement
      for the rate of drug discovery, allowing the activity of millions of compounds to
      be assessed through the testing of exponentially fewer samples. In this study, we
      used a scaffold-ranking library to screen 37 different libraries for
      antibacterial activity against the ESKAPE pathogens. Each library contained
      between 10000 and 750000 structural analogues for a total of >6 million
      compounds. From this, we identified a bis-cyclic guanidine library that displayed
      strong antibacterial activity. A positional scanning library for these compounds
      was developed and used to identify the most effective functional groups at each
      variant position. Individual compounds were synthesized that were broadly active
      against all ESKAPE organisms at concentrations <2 MUM. In addition, these
      compounds were bactericidal, had antibiofilm effects, showed limited potential
      for the development of resistance, and displayed almost no toxicity when tested
      against human lung cells and erythrocytes. Using a murine model of peritonitis,
      we also demonstrate that these agents are highly efficacious in vivo. 

PMID- 25780986
TI  - Legalizing physician-assisted suicide and/or euthanasia: Pragmatic implications-
      CORRIGENDUM.

PMID- 25780987
TI  - Synthesis of new heteroscorpionate iridium(I) and iridium(III) complexes.
AB  - The reactivity of different heteroscorpionate ligands based on bis(pyrazol-1
      yl)methane, with different iridium-(i) and -(iii) precursors is reported. The
      reaction of the heteroscorpionate lithium salts "Li(bdmpza)", [bdmpza = bis(3,5
      dimethylpyrazol-1-yl)acetate], "Li(bdmpzdta)" [bdmpzdta = bis(3,5-dimethylpyrazol
      1-yl)dithioacetate] and "Li(S)-mbpam" [(S)-mbpam = (S)-(-)-N-alpha-methylbenzyl
      2,2-bis(3,5-dimethylpyrazol-1-yl)acetamidate] with 1 equivalent of [IrCl3(THF)3]
      in THF for 18 h affords high yields of neutral and anionic heteroscorpionate
      chloride iridium complexes [IrCl2(bdmpza)(THF)] (), [Li(THF)4][IrCl3(bdmpzdta)]
      () and [IrCl2{(S)-mbpam})(THF)] (). Solution of complex in acetonitrile at room
      temperature leads to complex [IrCl2{(S)-mbpam})(NCCH3)] (). Complexes and were
      isolated as enantiopure compounds. The reaction of the lithium salt "Li(bdmpza)"
      with [IrCl(eta(4)-CH2[double bond, length as m-dash]C(Me)C(Me)[double bond,
      length as m-dash]CH2)]2 in THF for 18 h gave the Ir(i) complex [Ir(bdmpza)(eta(4)
      CH2[double bond, length as m-dash]C(Me)C(Me)[double bond, length as m-dash]CH2)]
      (). The reaction of complex with CO (2 atm) at room temperature leads to a new
      complex of Ir(iii), [Ir(bdmpza)(k(2)-CH2C(Me)[double bond, length as m
      dash]C(Me)CH2)(CO)] (). Treatment of heteroscorpionate ligand precursors
      "Li(bdmpza)" and "Li(bdmpzdta)" with [IrCp*Cl2]2 in THF yielded the iridium(iii)
      complexes [Ir2Cp*2Cl2(bdmpzx)] (x = a , x = dta ). These complexes have helical
      chirality due to the demands of the fixed pyrazole rings. The stereoisomerism and
      the self-assembly processes of these helicates have been studied in some detail
      in solution by NMR spectroscopy and in the solid state by X-ray diffraction.
      Mixtures of M- and P-handed enantiomers were obtained. Complex undergoes a
      decarboxylation process initiated by the HCl generated in the previous step
      leading to the known ionic complex [IrClCp*(bdmpm)][IrCl3Cp*] [bdmpm = bis(3,5
      dimethylpyrazol-1-yl)methane] (). The structures of the complexes were determined
      by spectroscopic methods and the X-ray crystal structures of , , and were also
      established. 

PMID- 25780988
TI  - Microstructure of transparent strontium fresnoite glass-ceramics.
AB  - Glass-ceramics grown from a glass of the composition Sr2TiSi2.45O8.9 (STS 45) are
      analyzed by scanning electron microscopy (SEM) and electron backscatter
      diffraction (EBSD). Oriented nucleation with the c-axes preferably perpendicular
      to the surface is detected. A very strong 001-texture is observed after only 10
      MUm of growth into the bulk, making this the first system in which an orientation
      preferred during nucleation prevails during growth into the bulk in glass
      ceramics. Piezoelectric measurements are performed and d33-values presented and
      discussed. The obtained results are critically viewed with respect to the two
      growth models describing Sr2TiSi2O8 growth in glasses.

PMID- 25780990
TI  - Histopathological findings in the peritumoral edema area of human glioma.
AB  - Peritumoral brain edema (PTBE) is considered to be one of the main biological
      behaviors of brain glioma. However, the histopathological features of PTBE remain
      imprecisely defined. We analyzed the histopathological characteristics in the
      PTBE area of 22 cases of glioma. Microscopically, the pre-existing basic
      structure in the edema area was still preserved but there were varying degrees of
      loose tissue. The main components of the edema tissue were scattered invasive
      tumor cells, reactive cells, and various blood vessel patterns. Invasive tumor
      cell density was significantly higher in high-grade glioma than in low-grade
      glioma, and the density was significantly higher in the area near compared to the
      area far from the glioma. The Ki-67 proliferative index of the invasive tumor
      cells was higher in high-grade glioma than in low-grade glioma, but the index was
      not different in the area near compared to the area far from the glioma. The
      microvessel pattern in PTBE was primarily branching capillary. The microvessel
      densities (MVDs) of CD34+ and CD105+ were higher in high-grade glioma and the
      area near the glioma than in low-grade glioma and the area far from the glioma.
      Compared to CD34+, the MVD of CD105+ exhibited a more significant downward trend
      in terms of distance from the glioma. The most obvious types of reactive cells
      were reactive astrocytes and activated microglia. The reactive astrocytes were
      positive for nestin. The activated microglia emerged in the area near the glioma
      in most cases and in the area far from the glioma in more than half of the cases.
      In addition, several cases displayed focal collections of small lymphocytes
      around small blood vessels and tumor cells arranged around a neuronal cell, and a
      limited number of cases displayed giant dysmorphic neurons in an edematous
      cortex. Our data indicate that PTBE is a consequence of tissue reconstruction
      resulting from tumor cell invasion and is an appropriate niche for the growth and
      spread of glioma cells. 

PMID- 25780991
TI  - Exploring views on current and future cochlear implant service delivery: the
      perspectives of users, parents and professionals at cochlear implant centres and
      in the community.
AB  - OBJECTIVE: The objective of this survey was to explore the perceptions of implant
      users/carers and professionals across the UK about current and future cochlear
      implant service delivery and the challenges. METHODS: Data were collected via an
      online questionnaire consisting of totally 22 questions. The questionnaire
      contained both open- and close-ended questions. RESULTS: Totally, seven hundred
      and forty-eight responses were received. In spite of the wide range of
      respondents, there was a broad consensus of opinion across groups. The majority
      of participants were satisfied with the service they currently receive, but
      wanted some changes. They reported their current experience of implant services
      to be mainly driven by decisions made by the implant team. For the future, they
      preferred the service to be mainly driven by decisions made jointly by the team
      and the user and/or parent/carer. The majority of participants wanted the
      cochlear implant services to be integrated into local audiology and other
      services such as education. Restrictions on number of candidates funded and
      political decisions and issues were seen as major challenges. Qualitative
      analysis of the open-ended responses supported the questionnaire responses.
      CONCLUSIONS: This research highlighted the benefits and limitations of the
      current cochlear implant service delivery as well as the potential implications
      for the long term. While respondents were generally happy with the current
      cochlear implant service provision, they expressed some concerns about the long
      term sustainability and management, wanting integration into the local services,
      and more involvement of parents and users in decisions.

PMID- 25780993
TI  - Priming effect of abscisic acid on alkaline stress tolerance in rice (Oryza
      sativa L.) seedlings.
AB  - Saline-alkaline stress is characterized by high salinity and high alkalinity
      (high pH); alkaline stress has been shown to be the primary factor inhibiting
      rice seedling growth. In this study, we investigated the potential priming effect
      of abscisic acid (ABA) on tolerance of rice seedlings to alkaline stress
      simulated by Na2CO3. Seedlings were pretreated with ABA at concentrations of 0
      (control), 10, and 50 MUM by root-drench for 24 h and then transferred to a
      Na2CO3 solution that did not contain ABA. Compared to control treatment,
      pretreatment with ABA substantially improved the survival rate of rice seedlings
      and increased biomass accumulation after 7 days under the alkaline condition. ABA
      application at 10 MUM also alleviated the inhibitory effects of alkaline stress
      on the total root length and root surface area. Physiologically, ABA increased
      relative water content (RWC) and decreased cell membrane injury degree (MI) and
      Na(+)/K(+) ratios. In contrast, fluridone (an ABA biosynthesis inhibitor)
      decreased the RWC and increased MI in shoots under the alkaline conditions. These
      data suggest that ABA has a potent priming effect on the adaptive response to
      alkaline stress in rice and may be useful for improving rice growth in saline
      alkaline paddy fields.

PMID- 25780994
TI  - Extended pelvic lymph node dissection for clinically localized prostate cancer: a
      West Australian experience.
AB  - BACKGROUND: The role and type of pelvic lymph node dissection for clinically
      localized prostate cancer is controversial in Australia. Our study aims to
      determine the incidence of pelvic lymph node involvement and the complication
      rate of extended lymphadenectomy in a group of West Australian patients who
      underwent a robotic assisted radical prostatectomy plus extended pelvic lymph
      node dissection. METHOD: Forty-nine patients underwent a robotic assisted radical
      prostatectomy with extended pelvic lymph node dissection between 2008 and 2012 by
      a single private urological surgeon. The inclusion criteria for the extended
      lymph node dissection were clinical localized, intermediate and high-risk
      prostate cancer based on preoperative D'Amico classification. RESULTS: Of the 49
      patients, eight patients had positive nodes giving a nodal positivity rate of
      16.33%. Six patients had a complication giving a total complication rate of
      12.24%. Three of these complications have been attributed to the nodal
      dissection, thus giving an extended pelvic lymph node dissection complication
      rate of 6.12%. CONCLUSION: Rates of nodal involvement in our West Australian
      cohort are in keeping with those published in the literature. Extended pelvic
      lymph node dissection can be performed with an acceptable complication rate.
      Further research is required to investigate the therapeutic role of pelvic lymph
      node dissection.

PMID- 25780995
TI  - Oscillation of the velvet worm slime jet by passive hydrodynamic instability.
AB  - The rapid squirt of a proteinaceous slime jet endows velvet worms (Onychophora)
      with a unique mechanism for defence from predators and for capturing prey by
      entangling them in a disordered web that immobilizes their target. However, to
      date, neither qualitative nor quantitative descriptions have been provided for
      this unique adaptation. Here we investigate the fast oscillatory motion of the
      oral papillae and the exiting liquid jet that oscillates with frequencies f~30-60
      Hz. Using anatomical images, high-speed videography, theoretical analysis and a
      physical simulacrum, we show that this fast oscillatory motion is the result of
      an elastohydrodynamic instability driven by the interplay between the elasticity
      of oral papillae and the fast unsteady flow during squirting. Our results
      demonstrate how passive strategies can be cleverly harnessed by organisms, while
      suggesting future oscillating microfluidic devices, as well as novel ways for
      micro and nanofibre production using bioinspired strategies. 

PMID- 25780996
TI  - Socioeconomic status as a possible moderator of neurocognitive outcomes in
      children with cancer.

PMID- 25780997
TI  - The influence of spray cryotherapy on wound healing following endoscopic sinus
      surgery in chronic rhinosinusitis.
AB  - OBJECTIVES/HYPOTHESIS: The aim of this study was to assess the influence of spray
      cryotherapy on wound healing following endoscopic sinus surgery (ESS). STUDY
      DESIGN: A prospective, randomized, double-blinded, controlled trial. METHODS: The
      study included 22 consecutive adult patients with chronic rhinosinusitis with and
      without polyps scheduled for bilateral ESS. At the end of the surgical procedure,
      patients were randomized to the distribution of spray cryotherapy in one middle
      meatus and saline contralaterally. Outcomes were only measured for endoscopy
      scores. Thus, postoperative healing and the amount of edema, crusting,
      secretions, and scarring were assessed using the validated Lund-Kennedy and
      Perioperative Sinus Endoscopy (POSE) scores. RESULTS: There were no baseline
      differences concerning POSE and Lund-Kennedy scores between the two groups.
      Nevertheless, a significant difference was recorded at one, 2, 4, 8, and 12 weeks
      in both POSE (P = .001, P = .012, P = .02, P = .006, P = .001) and Lund-Kennedy
      (P = .002, P = .005, P = .02, P = .02, P = .03) scores. CONCLUSIONS: These
      preliminary results reveal an improvement in postoperative scores, demonstrating
      enhanced healing following spray cryotherapy. However, without patient subjective
      outcomes, the study is limited. Additional studies with longer follow-up and
      larger samples are needed to describe the effects of cryotherapy on wound
      healing.

PMID- 25780998
TI  - Device for dielectrophoretic separation and collection of nanoparticles and DNA
      under high conductance conditions.
AB  - Most dielectrophoretic (DEP) separations of cells, nanoparticles, and other
      entities are carried out on microelectrode arrays or in microfluidic device
      formats. Less work has been directed at designing pipette-type formats that would
      allow dipping into and recovering specific analytes from samples in microtiter
      plate formats. In order to address this important area, we have fabricated
      micropipette tip devices containing a 2% agarose gel plug, a buffer chamber, and
      platinum electrode as the DEP collection device, to be used in combination with
      separate sample wells that contain a circular gold electrode. We demonstrated
      that 200 nm fluorescent nanoparticles could be isolated into DEP high-field
      regions and separated from 10 MUm fluorescent microbeads in high conductance
      buffer (1* PBS) by applying an alternating current at 10 kHz with a peak-to-peak
      voltage (Vpp) of 160 Vpp. The collected nanoparticles were then transferred to a
      new buffer solution. We also demonstrated the DEP isolation and separation of
      genomic DNA (>50 kbps) from the 10 MUm microbeads in high conductance buffer (1*
      PBS) with transfer of collected DNA to another solution. 

PMID- 25780999
TI  - Cryopreservation-induced alterations in protein composition of rainbow trout
      semen.
AB  - The aim of this study was to detect cryopreservation-induced alterations in the
      protein composition of rainbow trout semen using two independent methods 1DE SDS
      PAGE prefractionation combined with LC-MS/MS and 2D difference gel
      electrophoresis followed by MALDI-TOF/TOF identification. Here, we show the first
      comprehensive dataset of changes in rainbow trout semen proteome after
      cryopreservation, with a total of 73 identified proteins released from sperm to
      extracellular fluid, including mitochondrial, cytoskeletal, nuclear, and
      cytosolic proteins. Our study provides new information about proteins released
      from sperm, their relation to sperm structure and function, and changes of
      metabolism of sperm cells as a result of cryopreservation. The identified
      proteins represent potential markers of cryoinjures of sperm structures and
      markers of the disturbances of particular sperm metabolic pathways. Further
      studies will allow to decipher the precise function of the proteins altered
      during rainbow trout cryopreservation and are useful for the development of
      extensive diagnostic tests of sperm cryoinjures and for the successful
      improvement of sperm cryopreservation of this economically important species. 

PMID- 25781001
TI  - Development of an adaptive monitoring framework for long-term programs: An
      example using indicators of fish health.
AB  - Detecting unwanted changes associated with localized human activities in aquatic
      ecosystems requires defining the value of an indicator expected at a site in the
      absence of development. Ideally, adequate and comparable baseline data will be
      collected at an exposure location before that development, but this is rarely
      done. Instead, comparisons are made using various designs to overcome the
      inadequate or missing baseline data. Commonly these comparisons are done over
      short periods, using information from local reference sites to estimate
      variability expected at the exposed site. Results of these truncated designs are
      often evaluated using p values that may have little bearing on ecologically
      relevant changes. To remedy the reliance of studies on small datasets collected
      at reference sites, other designs emphasize regional analyses, but these may be
      insensitive to site-specific changes. Some designs also may forego discussing the
      consequences of detecting any differences. A new monitoring framework has been
      proposed to use existing solutions, simplify analysis, and focus on the detection
      of meaningful changes. It is illustrated here by using data on fish health from a
      large-scale, long-term program in the Moose River basin in northern Ontario. This
      framework advocates interpretation of data at multiple scales: within-site,
      locally, and regionally. The primary focus is on estimating a range from a
      probability distribution of historical data collected at a specific location
      where 95% of future observations are predicted to occur. Changes at the exposed
      site are also compared with historical and contemporary expectations from
      proximate and regional reference sites. Critical effect sizes also can be derived
      from regional reference data to evaluate the magnitude of differences observed
      between any 2 sites. Any unexpected changes inform future monitoring decisions
      provided by a priori guidance. Adoption of this framework extends the utility of
      monitoring programs in which commitments to long-term collections have been made,
      advocates harmonization of studies over time and space, and focuses attention on
      unusual observations.

PMID- 25781000
TI  - Inhibition of presynaptic calcium transients in cortical inputs to the
      dorsolateral striatum by metabotropic GABA(B) and mGlu2/3 receptors.
AB  - Cortical inputs to the dorsolateral striatum (DLS) are dynamically regulated
      during skill learning and habit formation, and are dysregulated in disorders
      characterized by impaired action control. Therefore, a mechanistic investigation
      of the processes regulating corticostriatal transmission is key to understanding
      DLS-associated circuit function, behaviour and pathology. Presynaptic GABA(B) and
      group II metabotropic glutamate (mGlu2/3) receptors exert marked inhibitory
      control over corticostriatal glutamate release in the DLS, yet the signalling
      pathways through which they do so are unclear. We developed a novel approach
      using the genetically encoded calcium (Ca(2+) ) indicator GCaMP6 to assess
      presynaptic Ca(2+) in corticostriatal projections to the DLS. Using simultaneous
      photometric presynaptic Ca(2+) and striatal field potential recordings, we report
      that relative to P/Q-type Ca(2+) channels, N-type channels preferentially
      contributed to evoked presynaptic Ca(2+) influx in motor cortex projections to,
      and excitatory transmission in, the DLS. Activation of GABA(B) or mGlu2/3
      receptors inhibited both evoked presynaptic Ca(2+) transients and striatal field
      potentials. mGlu2/3 receptor-mediated depression did not require functional N
      type Ca(2+) channels, but was attenuated by blockade of P/Q-type channels. These
      findings reveal presynaptic mechanisms of inhibitory modulation of
      corticostriatal function that probably contribute to the selection and shaping of
      behavioural repertoires.

PMID- 25781002
TI  - Biokinetics and metallothionein-like proteins response in oysters facing metal
      challenges in an estuary.
AB  - The discovery of colored oysters in an estuary in Southern China raised questions
      of how these oysters could survive in such an unpredictable estuary. In the
      present study, the authors conducted a transplant experiment using oysters
      Crassostrea hongkongensis in the estuary to quantify the changes of metal
      biokinetics (Cd and Zn) and the responses of metallothionein-like proteins.
      Oysters in the transplantation experiment accumulated extremely high
      concentrations of Cd, Cu, Cr, Ni, and Zn. The present study provided the field
      evidence of the time-course coupling relationship between Cd and Zn
      bioaccumulation. Over the 2-mo transplantation, the uptake rate constants of Cd
      and Zn varied greatly during the early stage of exposure but subsequently became
      comparable among the different locations. The dietary Zn assimilation remained
      relatively constant, whereas the Cd assimilation increased gradually with
      increasing period of exposure. No notable difference was seen in dietary metal
      assimilation among the different locations. In contrast, the efflux rates
      quantified by the end of transplantation were 26% to 42% higher for Cd and 12% to
      37% higher for Zn than that in the unexposed oysters. The authors further
      demonstrated that the incoming Cu and Zn were not stored in metallothionein-like
      pools and that metallothionein-like proteins synthesis and breakdown were little
      affected by metal exposure. Overall, the authors' transplantation experiments
      suggested that oysters displayed a rather weak ability to modify their
      biokinetics and metallothionein turnover under metal exposure.

PMID- 25781003
TI  - Young children's ability to use two-dimensional and three-dimensional symbols to
      show placements of body touches and hidden objects.
AB  - In two experiments, we investigated 3- to 5-year-old children's ability to use
      dolls and human figure drawings as symbols to map body touches. In Experiment 1,
      stickers were placed on different locations of children's bodies, and the
      children were asked to indicate the locations of the stickers using three
      different symbols: a doll, a human figure drawing, and the adult researcher.
      Performance on the tasks increased with age, but many 5-year-olds did not attain
      perfect performance. Surprisingly, younger children made more errors on the two
      dimensional (2D) human figure drawing task compared with the three-dimensional
      (3D) doll and adult tasks. In Experiment 2, we compared children's ability to use
      3D and 2D symbols to indicate body touch as well as to guide their search for a
      hidden object. We replicated the findings of Experiment 1 for the body touch
      task; for younger children, 3D symbols were easier to use than 2D symbols.
      However, the reverse pattern was found for the object locations task, with
      children showing superior performance using 2D drawings over 3D models. Although
      children showed developmental improvements in using dolls and drawings to show
      where they were touched, less than two thirds of the 5-year-olds performed
      perfectly on the touch tasks. Both developmental and forensic implications of
      these results are discussed. 

PMID- 25781004
TI  - Temporal and spatial variations of wall shear stress in the entrance region of
      microvessels.
AB  - Using a simplified two-dimensional divider-channel setup, we simulate the
      development process of red blood cell (RBC) flows in the entrance region of
      microvessels to study the wall shear stress (WSS) behaviors. Significant temporal
      and spatial variation in WSS is noticed. The maximum WSS magnitude and the
      strongest variation are observed at the channel inlet due to the close cell-wall
      contact. From the channel inlet, both the mean WSS and variation magnitude
      decrease, with a abrupt drop in the close vicinity near the inlet and then a slow
      relaxation over a relatively long distance; and a relative stable state with
      approximately constant mean and variation is established when the flow is well
      developed. The correlations between the WSS variation features and the cell free
      layer (CFL) structure are explored, and the effects of several hemodynamic
      parameters on the WSS variation are examined. In spite of the model limitations,
      the qualitative information revealed in this study could be useful for better
      understanding relevant processes and phenomena in the microcirculation. 

PMID- 25781005
TI  - ZnO/NiO diode-based charge-trapping layer for flash memory featuring low-voltage
      operation.
AB  - A stacked oxide semiconductor of n-type ZnO/p-type NiO with diode behavior was
      proposed as the novel charge-trapping layer to enable low-voltage flash memory
      for green electronics. The memory performance outperforms that of other devices
      with high kappa and a nanocrystal-based charge-trapping layer in terms of a large
      hysteresis memory window of 2.02 V with +/-3 V program/erase voltage, a high
      operation speed of 1.88 V threshold voltage shift by erasing at -4 V for 1 ms,
      negligible memory window degradation up to 10(5) operation cycles, and 16.2%
      charge loss after 10 years of operation at 85  degrees C. The promising
      electrical characteristics can be explained by the negative conduction band
      offset with respect to Si of ZnO that is beneficial to electron injection and
      storage, the large number of trapping sites of NiO that act as other good storage
      media, and most importantly the built-in electric field between n-type ZnO and p
      type NiO that provides a favorable electric field for program and erase
      operation. The process of diode-based flash memory is fully compatible with
      incumbent VLSI technology, and utilization of the built-in electric field ushers
      in a new avenue of accomplishing green flash memory. 

PMID- 25781006
TI  - Iodine status assessment in children: spot urine iodine concentration reasonably
      reflects true twenty-four-hour iodine excretion only when scaled to creatinine.
AB  - BACKGROUND: Currently, the measurement of urinary iodine concentration (UIC,
      MUg/L) is the recommended parameter to assess iodine status, however, the
      dependency of UIC on urine volume may limit its use as an accurate parameter for
      monitoring iodine status in populations. Therefore, our objective was to compare
      two approaches for the assessment of urinary iodine excretion in spot urine
      samples: UIC (MUg/L) and a creatinine-scaled estimate of 24-hour iodine excretion
      (est24h-UIEcrea [MUg/d]) against actually measured 24-hour urinary iodine
      excretion rates (24h-UIE, MUg/d). METHODS: Urinary iodine and creatinine were
      measured both in 24-hour urine samples and parallel collected spot urine samples
      from 180 healthy participants of the DONALD Study, aged 6-18 years. 24h-UIE was
      used as quasi-reference for actual iodine status. Published 24-hour creatinine
      reference values served to calculate est24h-UIEcrea. Correlation analysis, cross
      classifications, and Bland-Altman plots were used to evaluate agreement between
      the different assessment approaches. RESULTS: Correlation coefficients of 24h-UIE
      with UIC (r=0.12, r=0.22; p=n.s.) were substantially weaker than with est24h
      UIEcrea (r=0.41, r=0.47; p<0.001) in the 6-12 year old and 13-18 year old groups,
      respectively. Cross-classification into opposite quartiles by UIC was 7% (6-12
      year old group) and 15% (13-18 year old group) versus 5% and 3% by est24h
      UIEcrea, respectively. Bland-Altman plots indicated greater deviation from 24h
      UIE for the UIC versus the est24h-UIEcrea approach. CONCLUSION: Our findings in
      children and adolescents clearly show a better comparability of real 24h-UIE with
      est24h-UIEcrea than with UIC. Whenever highest possible validity is required for
      iodine status assessment from spot urine sampling, the determination of est24h
      UIEcrea appears to be the more accurate monitoring approach.

PMID- 25781007
TI  - Illegals/Ilegales: Comparing Anti-Immigrant/Anti-Refugee Discourses in Australia
      and Spain.

PMID- 25781008
TI  - Antihypertensive treatment in the elderly.

PMID- 25781009
TI  - Analysis of resistance to antimicrobials and presence of virulence/stress
      response genes in Campylobacter isolates from patients with severe diarrhoea.
AB  - Campylobacter infections are a major cause of diarrhoea world-wide and two of the
      antimicrobials used for their control (erythromycin and ciprofloxacin) have been
      losing efficacy in recent years. In a sample of 174 genotyped isolates from the
      stools of patients with severe diarrhoea in Qatar, collected between 2005 and
      2012, 63.2% showed resistance to ciprofloxacin, 8.6% to erythromycin, 0.57% to
      chloramphenicol and all were sensitive to gentamycin. While 33.9% of isolates
      were sensitive to all four antimicrobials, 59.8% were resistant to at least one,
      6.3% were resistant to two and none showed resistance to three antimicrobials.
      There was no host sex- or age-dependence among isolates resistant to
      ciprofloxacin and erythromycin and no significant variation was found with the
      region of origin of the patients. All isolates were screened for the presence of
      3 virulence factors (ciaB, cadF and cdtB) and two stress-response factors (htrB
      and clpP), all of which were present in more than 50% of the isolates. Host sex-,
      age- and region of origin-dependent variations in prevalence were found for some
      of these factors. Data analysis for the combination of virulence factors and
      their effect on antimicrobial resistance indicated that the prevalence of
      resistance to both erythromycin and ciprofloxacin was higher in isolates
      harbouring ciaB but not clpP. Prevalence of resistance to ciprofloxacin was
      similar in clpP positive and negative isolates also possessing htrB, while for
      htrB-negative isolates prevalence was higher in the absence of clpP. These
      results are discussed and their implications are highlighted. 

PMID- 25781010
TI  - DNA methylation of the serotonin transporter gene in peripheral cells and stress
      related changes in hippocampal volume: a study in depressed patients and healthy
      controls.
AB  - Serotonin plays an important role in the etiology of depression. Serotonin is
      also crucial for brain development. For instance, animal studies have
      demonstrated that early disruptions in the serotonin system affect brain
      development and emotion regulation in later life. A plausible explanation is that
      environmental stressors reprogram the serotonin system through epigenetic
      processes by altering serotonin system gene expression. This in turn may affect
      brain development, including the hippocampus, a region with dense serotonergic
      innervations and important in stress-regulation. The aim of this study was to
      test whether greater DNA methylation in specific CpG sites at the serotonin
      transporter promoter in peripheral cells is associated with childhood trauma,
      depression, and smaller hippocampal volume. We were particularly interested in
      those CpG sites whose state of methylation in peripheral cells had previously
      been associated with in vivo measures of brain serotonin synthesis. Thirty-three
      adults with Major Depressive Disorder (MDD) (23 females) and 36 matched healthy
      controls (21 females) were included in the study. Depressive symptoms, childhood
      trauma, and high-resolution structural MRI for hippocampal volume were assessed.
      Site-specific serotonin transporter methylation was assessed using
      pyrosequencing. Childhood trauma, being male, and smaller hippocampal volume were
      independently associated with greater peripheral serotonin transporter
      methylation. Greater serotonin transporter methylation in the depressed group was
      observed only in SSRI-treated patients. These results suggest that serotonin
      transporter methylation may be involved in physiological gene-environment
      interaction in the development of stress-related brain alterations. The results
      provide some indications that site-specific serotonin transporter methylation may
      be a biomarker for serotonin-associated stress-related psychopathology. 

PMID- 25781011
TI  - Distinct mechanisms of inadequate erythropoiesis induced by tumor necrosis factor
      alpha or malarial pigment.
AB  - The role of infection in erythropoietic dysfunction is poorly understood. In
      children with P. falciparum malaria, the by-product of hemoglobin digestion in
      infected red cells (hemozoin) is associated with the severity of anemia which is
      independent of circulating levels of the inflammatory cytokine tumor necrosis
      alpha (TNF-alpha). To gain insight into the common and specific effects of TNF
      alpha and hemozoin on erythropoiesis, we studied the gene expression profile of
      purified primary erythroid cultures exposed to either TNF-alpha (10 ng/ml) or to
      hemozoin (12.5 MUg/ml heme units) for 24 hours. Perturbed gene function was
      assessed using co-annotation of associated gene ontologies and expression of
      selected genes representative of the profile observed was confirmed by real time
      PCR (rtPCR). The changes in gene expression induced by each agent were largely
      distinct; many of the genes significantly modulated by TNF-alpha were not
      affected by hemozoin. The genes modulated by TNF-alpha were significantly
      enriched for those encoding proteins involved in the control of type 1 interferon
      signalling and the immune response to viral infection. In contrast, genes induced
      by hemozoin were significantly enriched for functional roles in regulation of
      transcription and apoptosis. Further analyses by rtPCR revealed that hemozoin
      increases expression of transcription factors that form part of the integrated
      stress response which is accompanied by reduced expression of genes involved in
      DNA repair. This study confirms that hemozoin induces cellular stress on
      erythroblasts that is additional to and distinct from responses to inflammatory
      cytokines and identifies new genes that may be involved in the pathogenesis of
      severe malarial anemia. More generally the respective transcription profiles
      highlight the varied mechanisms through which erythropoiesis may be disrupted
      during infectious disease.

PMID- 25781012
TI  - Continuous theta burst stimulation over the left dorsolateral prefrontal cortex
      decreases medium load working memory performance in healthy humans.
AB  - The dorsolateral prefrontal cortex (DLPFC) plays a key role in working memory.
      Evidence indicates that transcranial magnetic stimulation (TMS) over the DLPFC
      can interfere with working memory performance. Here we investigated for how long
      continuous theta-burst stimulation (cTBS) over the DLPFC decreases working memory
      performance and whether the effect of cTBS on performance depends on working
      memory load. Forty healthy young subjects received either cTBS over the left
      DLPFC or sham stimulation before performing a 2-, and 3-back working memory
      letter task. An additional 0-back condition served as a non-memory-related
      control, measuring general attention. cTBS over the left DLPFC significantly
      impaired 2-back working memory performance for about 15 min, whereas 3-back and 0
      back performances were not significantly affected. Our results indicate that the
      effect of left DLPFC cTBS on working memory performance lasts for roughly 15 min
      and depends on working memory load. 

PMID- 25781014
TI  - Intractable headaches, ischemic stroke, and seizures are linked to the presence
      of anti-beta2GPI antibodies in patients with systemic lupus erythematosus.
AB  - BACKGROUND: Neuropsychiatric systemic lupus erythematosus (NPSLE) is a common and
      potentially fatal manifestation of SLE. Antiphospholipid antibodies (aPL) such as
      lupus anticoagulant (LA), anticardiolipin (aCL) and antibodies to
      beta2glycoprotein I (anti-beta2GPI), the most important aPL antigen, are thought
      to play a role in some forms of NPSLE. As of yet, their specific roles in NPSLE
      manifestations remain to be elucidated. METHODOLOGY/PRINCIPAL FINDINGS: 57 SLE
      patients (53 women) were assessed for LA, aCL and anti-beta2GPI twice, to
      determine persistent positivity. All patients were examined by neurology and
      psychiatry specialists. 69 healthy subjects were assessed as controls. NPSLE was
      diagnosed in 74% of patients. Headaches were the most prevalent manifestation of
      NPSLE (39%), followed by cerebrovascular disease (CVD) (23%), depressive
      disorders (19.0%), and seizures (14%). NPSLE and non-NPSLE patients showed
      comparable SLE activity and corticosteroid use. In 65% of patients
      neuropsychiatric manifestations preceded SLE diagnosis. aPL profiles of NPSLE
      patients and non-NPSLE patients were similar. Headaches and ischemic stroke were
      independently associated with anti-beta2GPI-IgM (OR=5.6; p<0.05), and seizures
      were linked to anti-beta2GPI-IgG (OR=11.3; p=0.01). CONCLUSIONS: In SLE patients,
      neuropsychiatric manifestations occur frequently and early, often before the
      disease is diagnosed. Autoantibodies to beta2GPI are linked to non-specific
      headaches, ischemic stroke and seizures, and show a better predictive value than
      aCL and LA. These findings may help to improve the diagnosis of NPSLE and should
      prompt further studies to characterize the role of anti-beta2GPI in the
      pathogenesis of this condition.

PMID- 25781015
TI  - Prevalence and diversity of small mammal-associated Bartonella species in rural
      and urban Kenya.
AB  - Several rodent-associated Bartonella species are human pathogens but little is
      known about their epidemiology. We trapped rodents and shrews around human
      habitations at two sites in Kenya (rural Asembo and urban Kibera) to determine
      the prevalence of Bartonella infection. Bartonella were detected by culture in
      five of seven host species. In Kibera, 60% of Rattus rattus were positive, as
      compared to 13% in Asembo. Bartonella were also detected in C. olivieri (7%),
      Lemniscomys striatus (50%), Mastomys natalensis (43%) and R. norvegicus (50%).
      Partial sequencing of the citrate synthase (gltA) gene of isolates showed that
      Kibera strains were similar to reference isolates from Rattus trapped in Asia,
      America, and Europe, but that most strains from Asembo were less similar. Host
      species and trapping location were associated with differences in infection
      status but there was no evidence of associations between host age or sex and
      infection status. Acute febrile illness occurs at high incidence in both Asembo
      and Kibera but the etiology of many of these illnesses is unknown. Bartonella
      similar to known human pathogens were detected in small mammals at both sites and
      investigation of the ecological determinants of host infection status and of the
      public health significance of Bartonella infections at these locations is
      warranted. 

PMID- 25781013
TI  - Multivariate and phylogenetic analyses assessing the response of bacterial mat
      communities from an ancient oligotrophic aquatic ecosystem to different scenarios
      of long-term environmental disturbance.
AB  - Understanding the response of bacterial communities to environmental change is
      extremely important in predicting the effect of biogeochemical modifications in
      ecosystem functioning. The Cuatro Cienegas Basin is an ancient oasis in the
      Mexican Chihuahuan desert that hosts a wide diversity of microbial mats and
      stromatolites that have survived in extremely oligotrophic pools with nearly
      constant conditions. However, thus far, the response of these unique microbial
      communities to long-term environmental disturbances remains unexplored. We
      therefore studied the compositional stability of these bacterial mat communities
      by using a replicated (3x) mesocosm experiment: a) Control; b) Fluct: fluctuating
      temperature; c) 40C: increase to 40 oC; d) UVplus: artificial increase in UV
      radiation; and f) UVmin: UV radiation protection. In order to observe the changes
      in biodiversity, we obtained 16S rRNA gene clone libraries from microbial mats at
      the end of the experiment (eight months) and analyzed them using multivariate and
      phylogenetic tools. Sequences were assigned to 13 major lineages, among which
      Cyanobacteria (38.8%) and Alphaproteobacteria (25.5%) were the most abundant. The
      less extreme treatments (Control and UVmin) had a more similar composition and
      distribution of the phylogenetic groups with the natural pools than the most
      extreme treatments (Fluct, 40C, and UVplus), which showed drastic changes in the
      community composition and structure, indicating a different community response to
      each environmental disturbance. An increase in bacterial diversity was found in
      the UVmin treatment, suggesting that protected environments promote the
      establishment of complex bacterial communities, while stressful environments
      reduce diversity and increase the dominance of a few Cyanobacterial OTUs (mainly
      Leptolyngbya sp) through environmental filtering. Mesocosm experiments using
      complex bacterial communities, along with multivariate and phylogenetic analyses
      of molecular data, can assist in addressing questions about bacterial responses
      to long-term environmental stress. 

PMID- 25781017
TI  - Correction: systematic cell-based phenotyping of missense alleles empowers rare
      variant association studies: a case for LDLR and myocardial infarction.

PMID- 25781016
TI  - The effect of low-level laser irradiation on sperm motility, and integrity of the
      plasma membrane and acrosome in cryopreserved bovine sperm.
AB  - BACKGROUND AND OBJECTIVE: Freezing changes sperm integrity remarkably.
      Cryopreservation involves cooling, freezing, and thawing and all these contribute
      to structural damage in sperm, resulting in reduced fertility potential. Low
      level laser irradiation (LLLI) could increase energy supply to the cell and cause
      reactive oxygen species reduction (ROS), contributing to the restoration of
      oxygen consumption and adenosine triphosphate synthesis (ATP) in the
      mitochondria. Our goal was to analyze the effects of low-level laser irradiation
      on sperm motility and integrity of the plasma membrane and acrosome in
      cryopreserved bovine sperm. STUDY DESIGN/MATERIALS AND METHODS: We analyzed 09
      samples of bull semen (Bos taurus indicus), divided into three groups: a control
      group without laser irradiation, a 4J group subjected to a laser irradiation dose
      of 4 joules, and a 6J group subjected to dose of 6 joules. Samples were divided
      for the analysis of cell viability and acrosomal membrane integrity using flow
      cytometry; another portion was used for motion analysis. Irradiation was
      performed in petri dishes of 30 mm containing 3 ml of semen by an aluminum
      gallium indium phosphide laser diode with a wavelength of 660 nm, 30 mW power,
      and energy of 4 and 6 joules for 80 and 120 seconds respectively. Subsequently,
      the irradiated and control semen samples were subjected to cryopreservation and
      analyzed by flow cytometry (7AAD and FITC-PSA) using the ISAS--Integrated Semen
      Analysis System. RESULTS: Flow cytometry showed an increase in the percentage of
      live sperm cells and acrosome integrity in relation to control cells when
      subjected to irradiation of low-power laser in two different doses of 4 and 6
      joules (p < 0.05). In the analysis of straightness, percentage of cell movement,
      and motility, a dose of 4 joules was more effective (p < 0.05). CONCLUSION: We
      conclude that LLLI may exert beneficial effects in the preservation of live
      sperm. A dose of 4 joules prior to cryopreservation was more effective than a
      dose of 6 joules in preserving sperm motility.

PMID- 25781018
TI  - Correction: development of beta-carotene rich maize hybrids through marker
      assisted introgression of beta-carotene hydroxylase allele.

PMID- 25781019
TI  - Innovative Bayesian and parsimony phylogeny of dung beetles (coleoptera,
      scarabaeidae, scarabaeinae) enhanced by ontology-based partitioning of
      morphological characters.
AB  - Scarabaeine dung beetles are the dominant dung feeding group of insects and are
      widely used as model organisms in conservation, ecology and developmental
      biology. Due to the conflicts among 13 recently published phylogenies dealing
      with the higher-level relationships of dung beetles, the phylogeny of this
      lineage remains largely unresolved. In this study, we conduct rigorous
      phylogenetic analyses of dung beetles, based on an unprecedented taxon sample
      (110 taxa) and detailed investigation of morphology (205 characters). We provide
      the description of morphology and thoroughly illustrate the used characters.
      Along with parsimony, traditionally used in the analysis of morphological data,
      we also apply the Bayesian method with a novel approach that uses anatomy
      ontology for matrix partitioning. This approach allows for heterogeneity in
      evolutionary rates among characters from different anatomical regions. Anatomy
      ontology generates a number of parameter-partition schemes which we compare using
      Bayes factor. We also test the effect of inclusion of autapomorphies in the
      morphological analysis, which hitherto has not been examined. Generally, schemes
      with more parameters were favored in the Bayesian comparison suggesting that
      characters located on different body regions evolve at different rates and that
      partitioning of the data matrix using anatomy ontology is reasonable; however,
      trees from the parsimony and all the Bayesian analyses were quite consistent. The
      hypothesized phylogeny reveals many novel clades and provides additional support
      for some clades recovered in previous analyses. Our results provide a solid basis
      for a new classification of dung beetles, in which the taxonomic limits of the
      tribes Dichotomiini, Deltochilini and Coprini are restricted and many new tribes
      must be described. Based on the consistency of the phylogeny with biogeography,
      we speculate that dung beetles may have originated in the Mesozoic contrary to
      the traditional view pointing to a Cenozoic origin. 

PMID- 25781020
TI  - Information seeking regarding tobacco and lung cancer: effects of seasonality.
AB  - This paper conducted one of the first comprehensive international Internet
      analyses of seasonal patterns in information seeking concerning tobacco and lung
      cancer. Search query data for the terms "tobacco" and "lung cancer" from January
      2004 to January 2014 was collected from Google Trends. The relevant countries
      included the USA, Canada, the UK, Australia, and China. Two statistical
      approaches including periodogram and cross-correlation were applied to analyze
      seasonal patterns in the collected search trends and their associations. For
      these countries except China, four out of six cross-correlations of seasonal
      components of the search trends regarding tobacco were above 0.600. For these
      English-speaking countries, similar patterns existed in the data concerning lung
      cancer, and all cross-correlations between seasonal components of the search
      trends regarding tobacco and that regarding lung cancer were also above 0.700.
      Seasonal patterns widely exist in information seeking concerning tobacco and lung
      cancer on an international scale. The findings provide a piece of novel Internet
      based evidence for the seasonality and health effects of tobacco use. 

PMID- 25781021
TI  - The porcine microRNA transcriptome response to transmissible gastroenteritis
      virus infection.
AB  - Transmissible gastroenteritis virus (TGEV; Coronaviridae family) causes huge
      economic losses to the swine industry. MicroRNAs (miRNAs) play a regulatory role
      in viral infection and may be involved in the mammalian immune response. Here, we
      report a comprehensive analysis of host miRNA expression in TGEV-infected swine
      testis (ST) cells. Deep sequencing generated 3,704,353 and 2,763,665 reads from
      uninfected ST cells and infected ST cells, respectively. The reads were aligned
      to known Sus scrofa pre-miRNAs in miRBase 19, identifying 284 annotated miRNAs.
      Certain miRNAs were differentially regulated during TGEV infection. 59 unique
      miRNAs displayed significant differentially expression between the normal and
      TGEV-infected ST cell samples: 15 miRNAs were significantly up-regulated and 44
      were significantly down-regulated. Stem-loop RT-PCR was carried out to determine
      the expression levels of specific miRNAs in the two samples, and the results were
      consistent with those of sequencing. Gene ontology enrichment analysis of host
      target genes demonstrated that the differentially expressed miRNAs are involved
      in regulatory networks, including cellular process, metabolic process, immune
      system process. This is the first report of the identification of ST cell miRNAs
      and the comprehensive analysis of the miRNA regulatory mechanism during TGEV
      infection, which revealed the miRNA molecular regulatory mechanisms for the viral
      infection, expression of viral genes and the expression of immune-related genes.
      The results presented here will aid research on the prevention and treatment of
      viral diseases. 

PMID- 25781022
TI  - Unraveling antimicrobial resistance genes and phenotype patterns among
      Enterococcus faecalis isolated from retail chicken products in Japan.
AB  - Multidrug-resistant enterococci are considered crucial drivers for the
      dissemination of antimicrobial resistance determinants within and beyond a genus.
      These organisms may pass numerous resistance determinants to other harmful
      pathogens, whose multiple resistances would cause adverse consequences.
      Therefore, an understanding of the coexistence epidemiology of resistance genes
      is critical, but such information remains limited. In this study, our first
      objective was to determine the prevalence of principal resistance phenotypes and
      genes among Enterococcus faecalis isolated from retail chicken domestic products
      collected throughout Japan. Subsequent analysis of these data by using an
      additive Bayesian network (ABN) model revealed the co-appearance patterns of
      resistance genes and identified the associations between resistance genes and
      phenotypes. The common phenotypes observed among E. faecalis isolated from the
      domestic products were the resistances to oxytetracycline (58.4%),
      dihydrostreptomycin (50.4%), and erythromycin (37.2%), and the gene tet(L) was
      detected in 46.0% of the isolates. The ABN model identified statistically
      significant associations between tet(L) and erm(B), tet(L) and ant(6)-Ia, ant(6)
      Ia and aph(3')-IIIa, and aph(3')-IIIa and erm(B), which indicated that a multiple
      resistance profile of tetracycline, erythromycin, streptomycin, and kanamycin is
      systematic rather than random. Conversely, the presence of tet(O) was only
      negatively associated with that of erm(B) and tet(M), which suggested that in the
      presence of tet(O), the aforementioned multiple resistance is unlikely to be
      observed. Such heterogeneity in linkages among genes that confer the same
      phenotypic resistance highlights the importance of incorporating genetic
      information when investigating the risk factors for the spread of resistance. The
      epidemiological factors that underlie the persistence of systematic multiple
      resistance patterns warrant further investigations with appropriate adjustments
      for ecological and bacteriological factors. 

PMID- 25781023
TI  - Viridans Group Streptococci clinical isolates: MALDI-TOF mass spectrometry versus
      gene sequence-based identification.
AB  - Viridans Group Streptococci (VGS) species-level identification is fundamental for
      patients management. Matrix-assisted laser desorption ionization-time of flight
      mass spectrometry (MALDI-TOF MS) has been used for VGS identification but
      discrimination within the Mitis group resulted difficult. In this study, VGS
      identifications with two MALDI-TOF instruments, the Biotyper (Bruker) and the
      VITEK MS (bioMerieux) have been compared to those derived from tuf, soda and rpoB
      genes sequencing. VGS isolates were clustered and a dendrogram constructed using
      the Biotyper 3.0 software (Bruker). RpoB gene sequencing resulted the most
      sensitive and specific molecular method for S. pneumonia identification and was
      used as reference method. The sensitivity and the specificity of the VITEK MS in
      S. pneumonia identification were 100%, while the Biotyper resulted less specific
      (92.4%). In non pneumococcal VGS strains, the group-level correlation between
      rpoB and the Biotyper was 100%, while the species-level correlation was 61% after
      database upgrading (than 37% before upgrading). The group-level correlation
      between rpoB and the VITEK MS was 100%, while the species-level correlation was
      36% and increases at 69% if isolates identified as S. mitis/S. oralis are
      included. The less accurate performance of the VITEK MS in VGS identification
      within the Mitis group was due to the inability to discriminate between S. mitis
      and S. oralis. Conversely, the Biotyper, after the release of the upgraded
      database, was able to discriminate between the two species. In the dendrogram,
      VGS strains from the same group were grouped into the same cluster and had a good
      correspondence with the gene-based clustering reported by other authors, thus
      confirming the validity of the upgraded version of the database. Data from this
      study demonstrated that MALDI-TOF technique can represent a rapid and cost saving
      method for VGS identification even within the Mitis group but improvements of
      spectra database are still recommended. 

PMID- 25781024
TI  - Correlation between relaxometry and diffusion tensor imaging in the globus
      pallidus of Huntington's disease patients.
AB  - Huntington's disease (HD) is an inherited neurodegenerative disorder with
      progressive impairment of motor, behavioral and cognitive functions. The clinical
      features of HD are closely related to the degeneration of the basal ganglia,
      predominantly the striatum. The main striatal output structure, the globus
      pallidus, strongly accumulates metalloprotein-bound iron, which was recently
      shown to influence the diffusion tensor scalar values. To test the hypothesis
      that this effect dominates in the iron-rich basal ganglia of HD patients, we
      examined the globus pallidus using DTI and T2 relaxometry sequences. Quantitative
      magnetic resonance (MR), clinical and genetic data (number of CAG repeats) were
      obtained from 14 HD patients. MR parameters such as the T2 relaxation rate (RR),
      fractional anisotropy (FA) and mean diffusivity (MD) were analysed. A positive
      correlation was found between RR and FA (R2=0.84), between CAG and RR (R2=0.59)
      and between CAG and FA (R2=0.44). A negative correlation was observed between RR
      and MD (R2=0.66). A trend towards correlation between CAG and MD was noted. No
      correlation between MR and clinical parameters was found. Our results indicate
      that especially magnetic resonance FA measurements in the globus pallidus of HD
      patients may be strongly affected by metalloprotein-bound iron accumulation. 

PMID- 25781025
TI  - A randomised controlled trial of intravenous zoledronic acid in malignant pleural
      disease: a proof of principle pilot study.
AB  - INTRODUCTION: Animal studies have shown Zoledronic Acid (ZA) may diminish pleural
      fluid accumulation and tumour bulk in malignant pleural disease (MPD). We
      performed a pilot study to evaluate its effects in humans. METHODS: We undertook
      a single centre, double-blind, placebo-controlled trial in adults with MPD.
      Patients were randomised (1:1) to receive 2 doses of intravenous ZA or placebo, 3
      weeks apart and were followed-up for 6 weeks. The co-primary outcomes were change
      in Visual Analogue Scale (VAS) score measured breathlessness during trial follow
      up and change in the initial area under the curve (iAUC) on thoracic Dynamic
      Contrast Enhanced Magnetic Resonance Imaging (DCE-MRI) from randomisation to week
      5. Multiple secondary endpoints were also evaluated. RESULTS: Between January
      2010 and May 2013, 30 patients were enrolled, 24 randomised and 4 withdrew after
      randomisation (1 withdrew consent; 3 had a clinical decline). At baseline, the ZA
      group were more breathless, had more advanced disease on radiology and worse
      quality of life than the placebo group. There was no significant difference
      between the groups with regards change in breathlessness (Adjusted mean
      difference (AMD) 4.16 (95%CI -4.7 to 13.0)) or change in DCE-MRI iAUC (AMD -15.4
      (95%CI -58.1 to 27.3). Two of nine (22%) in the ZA arm had a >10% improvement by
      modified RECIST (vs 0/11 who received placebo). There was no significant
      difference in quality of life measured by the QLQ-C30 score (global QOL: AMD -4.1
      (-13.0 to 4.9)), side effects or serious adverse event rates. CONCLUSIONS: This
      is the first human study to evaluate ZA in MPD. The study is limited by small
      numbers and imbalanced baseline characteristics. Although no convincing treatment
      effect was identified, potential benefits for specific subgroups of patients
      cannot be excluded. This study provides important information regarding the
      feasibility of future trials to evaluate the effects of ZA further. TRIAL
      REGISTRATION: UK Clinical Research Network ID 8877 ISRCTN17030426 www.isrctn.com.

PMID- 25781026
TI  - Inositol depletion restores vesicle transport in yeast phospholipid flippase
      mutants.
AB  - In eukaryotic cells, type 4 P-type ATPases function as phospholipid flippases,
      which translocate phospholipids from the exoplasmic leaflet to the cytoplasmic
      leaflet of the lipid bilayer. Flippases function in the formation of transport
      vesicles, but the mechanism remains unknown. Here, we isolate an arrestin-related
      trafficking adaptor, ART5, as a multicopy suppressor of the growth and endocytic
      recycling defects of flippase mutants in budding yeast. Consistent with a
      previous report that Art5p downregulates the inositol transporter Itr1p by
      endocytosis, we found that flippase mutations were also suppressed by the
      disruption of ITR1, as well as by depletion of inositol from the culture medium.
      Interestingly, inositol depletion suppressed the defects in all five flippase
      mutants. Inositol depletion also partially restored the formation of secretory
      vesicles in a flippase mutant. Inositol depletion caused changes in lipid
      composition, including a decrease in phosphatidylinositol and an increase in
      phosphatidylserine. A reduction in phosphatidylinositol levels caused by
      partially depleting the phosphatidylinositol synthase Pis1p also suppressed a
      flippase mutation. These results suggest that inositol depletion changes the
      lipid composition of the endosomal/TGN membranes, which results in vesicle
      formation from these membranes in the absence of flippases. 

PMID- 25781027
TI  - Comparison between different methods for biomechanical assessment of ex vivo
      fracture callus stiffness in small animal bone healing studies.
AB  - For ex vivo measurements of fracture callus stiffness in small animals, different
      test methods, such as torsion or bending tests, are established. Each method
      provides advantages and disadvantages, and it is still debated which of those is
      most sensitive to experimental conditions (i.e. specimen alignment, directional
      dependency, asymmetric behavior). The aim of this study was to experimentally
      compare six different testing methods regarding their robustness against
      experimental errors. Therefore, standardized specimens were created by selective
      laser sintering (SLS), mimicking size, directional behavior, and embedding
      variations of respective rat long bone specimens. For the latter, five different
      geometries were created which show shifted or tilted specimen alignments. The
      mechanical tests included three-point bending, four-point bending, cantilever
      bending, axial compression, constrained torsion, and unconstrained torsion. All
      three different bending tests showed the same principal behavior. They were
      highly dependent on the rotational direction of the maximum fracture callus
      expansion relative to the loading direction (creating experimental errors of more
      than 60%), however small angular deviations (<15 degrees ) were negligible.
      Differences in the experimental results between the bending tests originate in
      their respective location of maximal bending moment induction. Compared to four
      point bending, three-point bending is easier to apply on small rat and mouse
      bones under realistic testing conditions and yields robust measurements, provided
      low variation of the callus shape among the tested specimens. Axial compressive
      testing was highly sensitive to embedding variations, and therefore cannot be
      recommended. Although it is experimentally difficult to realize, unconstrained
      torsion testing was found to be the most robust method, since it was independent
      of both rotational alignment and embedding uncertainties. Constrained torsional
      testing showed small errors (up to 16.8%, compared to corresponding alignment
      under unconstrained torsion) due to a parallel offset between the specimens' axis
      of gravity and the torsional axis of rotation. 

PMID- 25781029
TI  - Tri-trophic effects of seasonally variable induced plant defenses vary across the
      development of a shelter building moth larva and its parasitoid.
AB  - Plant chemical defenses can negatively affect insect herbivore fitness, but they
      can also decrease herbivore palatability to predators or decrease parasitoid
      fitness, potentially changing selective pressures on both plant investment in
      production of chemical defenses and host feeding behavior. Larvae of the fern
      moth Herpetogramma theseusalis live in and feed upon leaf shelters of their own
      construction, and their most abundant parasitoid Alabagrus texanus oviposits in
      early instar larvae, where parasitoid larvae lay dormant for most of host
      development before rapidly developing and emerging just prior to host pupation.
      As such, both might be expected to live in a relatively constant chemical
      environment. Instead, we find that a correlated set of phenolic compounds shows
      strong seasonal variation both within shelters and in undamaged fern tissue, and
      the relative level of these compounds in these two different fern tissue types
      switches across the summer. Using experimental feeding treatments, in which we
      exposed fern moth larvae to different chemical trajectories across their
      development, we show that exposure to this set of phenolic compounds reduces the
      survival of larvae in early development. However, exposure to this set of
      compounds just before the beginning of explosive parasitoid growth increased
      parasitoid survival. Exposure during the period of rapid parasitoid growth and
      feeding decreased parasitoid survival. These results highlight the spatial and
      temporal complexity of leaf shelter chemistry, and demonstrate the developmental
      contingency of associated effects on both host and parasitoid, implying the
      existence of complex selective pressures on plant investment in chemical
      defenses, host feeding behavior, and parasitoid life history. 

PMID- 25781028
TI  - When chocolate seeking becomes compulsion: gene-environment interplay.
AB  - BACKGROUND: Eating disorders appear to be caused by a complex interaction between
      environmental and genetic factors, and compulsive eating in response to adverse
      circumstances characterizes many eating disorders. MATERIALS AND METHODS: We
      compared compulsion-like eating in the form of conditioned suppression of
      palatable food-seeking in adverse situations in stressed C57BL/6J and DBA/2J
      mice, two well-characterized inbred strains, to determine the influence of gene
      environment interplay on this behavioral phenotype. Moreover, we tested the
      hypothesis that low accumbal D2 receptor (R) availability is a genetic risk
      factor of food compulsion-like behavior and that environmental conditions that
      induce compulsive eating alter D2R expression in the striatum. To this end, we
      measured D1R and D2R expression in the striatum and D1R, D2R and alpha1R levels
      in the medial prefrontal cortex, respectively, by western blot. RESULTS: Exposure
      to environmental conditions induces compulsion-like eating behavior, depending on
      genetic background. This behavioral pattern is linked to decreased availability
      of accumbal D2R. Moreover, exposure to certain environmental conditions
      upregulates D2R and downregulates alpha1R in the striatum and medial prefrontal
      cortex, respectively, of compulsive animals. These findings confirm the function
      of gene-environment interplay in the manifestation of compulsive eating and
      support the hypothesis that low accumbal D2R availability is a "constitutive"
      genetic risk factor for compulsion-like eating behavior. Finally, D2R
      upregulation and alpha1R downregulation in the striatum and medial prefrontal
      cortex, respectively, are potential neuroadaptive responses that parallel the
      shift from motivated to compulsive eating.

PMID- 25781030
TI  - Nonclinical evaluation of novel cationically modified polysaccharide antidotes
      for unfractionated heparin.
AB  - Protamine, the only registered antidote of unfractionated heparin (UFH), may
      produce a number of adverse effects, such as anaphylactic shock or serious
      hypotension. We aimed to develop an alternative UFH antidote as efficient as
      protamine, but safer and easier to produce. As a starting material, we have
      chosen generally non-toxic, biocompatible, widely available, inexpensive, and
      easy to functionalize polysaccharides. Our approach was to synthesize, purify and
      characterize cationic derivatives of dextran, hydroxypropylcellulose, pullulan
      and gamma-cyclodextrin, then to screen them for potential heparin-reversal
      activity using an in vitro assay and finally examine efficacy and safety of the
      most active polymers in Wistar rat and BALB/c mouse models of experimentally
      induced arterial and venous thrombosis. Efficacy studies included the measurement
      of thrombus formation, activated partial thromboplastin time, bleeding time, and
      anti-factor Xa activity; safety studies included the measurement of hemodynamic,
      hematologic and immunologic parameters. Linear, high molecular weight dextran
      substituted with glycidyltrimethylammonium chloride groups at a ratio of 0.65 per
      glucose unit (Dex40-GTMAC3) is the most potent and the safest UFH inhibitor
      showing activity comparable to that of protamine while possessing lower
      immunogenicity. Cationic polysaccharides of various structures neutralize UFH.
      Dex40-GTMAC3 is a promising and potentially better UFH antidote than protamine. 

PMID- 25781031
TI  - Impact of ten-valent pneumococcal conjugate vaccination on invasive pneumococcal
      disease in Finnish children--a population-based study.
AB  - BACKGROUND: The ten-valent pneumococcal conjugate vaccine (PCV10) was introduced
      into the Finnish National Vaccination Program (NVP) in September 2010 with a 2+1
      schedule (3, 5, 12 months) without catch-up vaccinations. We evaluated the direct
      and indirect effects of PCV10 on invasive pneumococcal disease (IPD) among
      children <=5 years of age during the first three years after NVP introduction.
      METHODS: We conducted a population-based, observational follow-up study. The
      cohort of vaccine-eligible children (all children born June 1, 2010 or later) was
      followed from 3 months of age until the end of 2013. For the indirect effect,
      another cohort of older children ineligible for PCV10 vaccination was followed
      from 2011 through 2013. Both cohorts were compared with season- and age-matched
      reference cohorts before NVP introduction. National, population-based laboratory
      surveillance data were used to compare culture-confirmed serotype-specific IPD
      rates in the vaccine target and reference cohorts by using Poisson regression
      models. RESULTS: The overall IPD rate among vaccine-eligible children was reduced
      by 80% (95%CI 72 to 85); the reduction in vaccine-type IPD was 92% (95%CI 86 to
      95). However, a non-significant increase in non-vaccine type IPD was observed.
      During 2012-2013, we also observed a 48% (95%CI 18 to 69) reduction in IPD among
      unvaccinated children 2 to 5 years of age, which was mostly attributable to the
      ten vaccine serotypes. CONCLUSIONS: This is the first population-based study
      investigating the impact of PCV10 introduction without prior PCV7 use. A
      substantial decrease in IPD rates among vaccine-eligible children was observed. A
      smaller and temporally delayed reduction among older, unvaccinated children
      suggests that PCV10 also provides indirect protection against vaccine-type IPD.
      Changes in serotype distribution warrant continuous monitoring of potential
      increases in non-vaccine serotypes.

PMID- 25781033
TI  - Palladium-catalyzed tandem annulation: a strategy to construct 2,3
      difunctionalized benzofuran derivatives in ionic liquids.
AB  - An efficient and ecofriendly method for the construction of 2,3-difunctionalized
      benzofuran derivatives in moderate to good yields from readily available 2
      alkynylphenols has been developed. This tandem annulation process, featuring one
      pot, three steps, good functional group tolerance, and high atom economy, makes
      this transformation efficient and practical. Moreover, this protocol is scalable,
      illustrating its potential applications in synthetic and pharmaceutical
      chemistry. 

PMID- 25781032
TI  - Assessment of the distribution, sources and potential ecological risk of heavy
      metals in the dry surface sediment of Aibi Lake in northwest China.
AB  - The distribution, sources and potential ecological risk of heavy metals in the
      sediment of lakes in eastern China and other areas of the world that have
      undergone rapid economic development have been widely researched by scholars.
      However, this is not true for heavy metals in the sediment of rump lakes in the
      arid regions of China and world-wide. Because of this, we chose Aibi Lake to
      serve as a typical rump lake in an oasis in an arid area in northwest China for
      our study. Sediment samples were collected from the lake and then the quantities
      of the heavy metals Pb, Ni, Cd, Cu, Zn, Hg and Cr were measured. Then using a
      variety of statistical methods, we analyzed the distribution, sources, pollution
      status and the potential ecological risk of these metals. The results show that:
      (1) The amounts of the seven heavy metals all fell within the Second Soil
      National Standard, but the average and maximum values were all higher than the
      background values of Xinjiang in northwest China. (2) Multivariate statistical
      analysis determined that the Cd, Pb, Hg and Zn in the sediment were mainly
      derived from man-sources, and Cu, Ni, and Cr were mainly from the natural
      geological background. (3) Enrichment factor analysis and the geo-accumulation
      index evaluation method show that Cd, Hg and Pb in the surface sediment of the
      Aibi Lake were at low and partial pollution levels, while Zn, Cr, Ni and Cu were
      at no and low pollution levels. (4) Calculation of the potential ecological
      hazards index found that, among the seven tested heavy metals, Cd, Hg and Pb were
      the main potential ecological risk factors, and the contribution of each was
      42.6%, 28.6%, and 24.0%, respectively. Cd is the main potential ecological risk
      factor, followed by Hg and Pb. This work revealed that recent economic
      development of the Aibi Lake Basin has negatively influenced the accumulation of
      heavy metals in the sediments of the lake, and, therefore, we should pay
      increasing attention to this problem and take effective measures to protect the
      ecology of the Aibi Lake Basin. This work can provide a scientific basis for an
      early warning of heavy metal pollution and for protection of the environment.
      Furthermore, it can serve as a reference when creating policies for the economic
      development in Aibi Lake Basin and environmental protection of rump lakes in arid
      regions of northwest China and other areas of the world. 

PMID- 25781034
TI  - Fabrication of periodic silicon nanopillars in a two-dimensional hexagonal array
      with enhanced control on structural dimension and period.
AB  - We present a method to fabricate well-controlled periodic silicon nanopillars (Si
      NPs) in hexagonal arrays using silica nanosphere (SNS) lithography (SNL) combined
      with metal-assisted chemical etching (MaCE). The period of the Si NPs is easily
      changed by using our silica nanosphere (SNS) spin-coating process, which provides
      excellent monolayer uniformity and coverage (>95%) over large surface areas. The
      size of the deposited SNS is adjusted by reactive ion etching (RIE) to produce a
      target diameter at a fixed period for control of the surface pattern size after a
      gold metal mask layer deposition. The Si NPs are etched with the MaCE technique
      following introduction of a Ni interfacial layer between the Si and Au catalyst
      layer for adhesion and improved lithographical accuracy. The result is a fast,
      convenient, and large-area applicable Si surface nanolithography technique for
      accurate and reproducible Si NP fabrication. 

PMID- 25781036
TI  - Magic ratios for connectivity-driven electrical conductance of graphene-like
      molecules.
AB  - Experiments using a mechanically controlled break junction and calculations based
      on density functional theory demonstrate a new magic ratio rule (MRR) that
      captures the contribution of connectivity to the electrical conductance of
      graphene-like aromatic molecules. When one electrode is connected to a site i and
      the other is connected to a site i' of a particular molecule, we assign the
      molecule a "magic integer" Mii'. Two molecules with the same aromatic core but
      different pairs of electrode connection sites (i,i' and j,j', respectively)
      possess different magic integers Mii' and Mjj'. On the basis of connectivity
      alone, we predict that when the coupling to electrodes is weak and the Fermi
      energy of the electrodes lies close to the center of the HOMO-LUMO gap, the ratio
      of their conductances is equal to (Mii'/Mjj')(2). The MRR is exact for a tight
      binding representation of a molecule and a qualitative guide for real molecules. 

PMID- 25781035
TI  - Evolutionary problems in centrosome and centriole biology.
AB  - Centrosomes have been an enigma to evolutionary biologists. Either they have been
      the subject of ill-founded speculation or they have been ignored. Here, we
      highlight evolutionary paradoxes and problems of centrosome and centriole
      evolution and seek to understand them in the light of recent advances in
      centrosome biology. Most evolutionary accounts of centrosome evolution have been
      based on the hypothesis that centrosomes are replicators, independent of the
      nucleus and cytoplasm. It is now clear, however, that this hypothesis is not
      tenable. Instead, centrosomes are formed de novo each cell division, with the
      presence of an old centrosome regulating, but not essential for, the assembly of
      a new one. Centrosomes are the microtubule-organizing centres of cells. They can
      potentially affect sensory and motor characters (as the basal body of cilia), as
      well as the movements of chromosomes during cell division. This latter role does
      not seem essential, however, except in male meiosis, and the reasons for this
      remain unclear. Although the centrosome is absent in some taxa, when it is
      present, its structure is extraordinarily conserved: in most taxa across
      eukaryotes, it does not appear to evolve at all. And yet a few insect groups
      display spectacular hypertrophy of the centrioles. We discuss how this might
      relate to the unusual reproductive system found in these insects. Finally, we
      discuss why the fate of centrosomes in sperm and early embryos might differ
      between different groups of animals.

PMID- 25781037
TI  - Systematic review of the predisposing, enabling, and reinforcing factors which
      influence nursing administration of opioids in the postoperative period.
AB  - AIM: To provide an overview of the administration of opioid analgesics by nurses
      when prescription is on an "as-needed" basis for postoperative pain, and to
      identify the important factors that determine the decisions of nurses, by using
      the framework of predisposing, reinforcing, and enabling causes in educational
      diagnosis and evaluation. METHODS: Multiple databases were searched for the
      period from 2000-2012. Out of a total of 1755 citations and 148 abstracts
      retrieved, 39 studies met the criteria for inclusion. Studies were considered
      eligible for review if they focused on situations or factors influencing a
      nurse's performance in pain assessment and the administration of opioid
      analgesics in postoperative pain management. RESULTS: The topics of the
      descriptive and qualitative studies presented four themes: (i) nurses' knowledge
      and attitudes about pain management; (ii) the situation of nurses' work practices
      in administrating range orders for opioid analgesics; (iii) factors that
      influenced nurses' work practices; and (iv) perceived barriers to effective pain
      management from the nurse's perspective. The experimental studies investigated
      the effects of different approaches in nurses' pain management practices in
      postoperative settings and their outcomes for patients. CONCLUSION: A knowledge
      deficit was observed to be the reason in most cases for a nurse's failure to
      administrate adequate analgesics for postoperative pain relief. Pain-related
      education for nurses is the cornerstone to improve pain management. The
      integration of enabling and reinforcing factors will help nurses to develop the
      ability to make the decision to engage in a comprehensive intervention to improve
      pain management and patient outcomes.

PMID- 25781038
TI  - Editorial: is thalidomide a good option for patients with refractory Crohn's
      disease?

PMID- 25781039
TI  - Editorial: is thalidomide a good option for patients with refractory Crohn's
      disease? Authors' reply.

PMID- 25781040
TI  - Editorial: chronic liver disease and deaths from peptic ulcer bleeding.

PMID- 25781041
TI  - Editorial: chronic liver disease and deaths from peptic ulcer bleeding - authors'
      reply.

PMID- 25781042
TI  - Letter: pre- and post-operative anti-viral therapy is important for patients with
      hepatitis B virus-related hepatocellular carcinoma.

PMID- 25781043
TI  - Letter: pre- and post-operative anti-viral therapy is important for patients with
      hepatitis B virus-related hepatocellular carcinoma - authors' reply.

PMID- 25781044
TI  - Letter: irritable bowel syndrome is significantly associated with somatisation -
      authors' reply.

PMID- 25781045
TI  - Letter: irritable bowel syndrome is significantly associated with somatisation.

PMID- 25781046
TI  - Letter: prompt endoscopy in Asians with uninvestigated dyspepsia.

PMID- 25781047
TI  - Letter: prompt endoscopy in Asians with uninvestigated dyspepsia - authors'
      reply.

PMID- 25781048
TI  - Letter: reversibility of hepatic fibrosis and immunosuppression withdrawal in
      patients with autoimmune hepatitis/primary biliary cirrhosis overlap syndrome -
      author's reply.

PMID- 25781049
TI  - Letter: reversibility of hepatic fibrosis and immunosuppression withdrawal in
      patients with autoimmune hepatitis/primary biliary cirrhosis overlap syndrome.

PMID- 25781050
TI  - Letter: metabolic syndrome in patients with coeliac disease on a gluten-free
      diet.

PMID- 25781051
TI  - Letter: metabolic syndrome in patients with coeliac disease on a gluten-free diet
      - authors' reply.

PMID- 25781052
TI  - Proresolving Action of Docosahexaenoic Acid Monoglyceride in Lung Inflammatory
      Models Related to Cystic Fibrosis.
AB  - Cystic fibrosis (CF) is a hereditary, chronic disease of the exocrine glands,
      characterized by the production of viscid mucus that obstructs the pancreatic
      ducts and bronchi, leading to infection and fibrosis. omega3 fatty acid
      supplementations are known to improve the essential fatty acid deficiency as well
      as reduce inflammation in CF. The objective of this study was to determine the
      effects of docosahexaenoic acid monoacylglyceride (MAG-DHA) on mucin
      overproduction and resolution of airway inflammation in two in vitro models
      related to CF. Isolated human bronchi reverse permeabilized with CF transmembrane
      conductance regulator (CFTR) silencing (si) RNA and stable Calu3 cells expressing
      a short hairpin (sh) RNA directed against CFTR (shCFTR) were used. Lipid analyses
      revealed that MAG-DHA increased DHA/arachidonic acid (AA) ratio in shCFTR Calu-3
      cells. MAG-DHA treatments, moreover, resulted in a decreased activation of
      Pseudomonas aeruginosa LPS-induced NF-kappaB in CF and non-CF Calu-3 cells. Data
      also revealed a reduction in MUC5AC, IL-6, and IL-8 expression levels in MAG-DHA
      treated shCFTR cells stimulated, or not, with LPS. Antiinflammatory properties of
      MAG-DHA were also investigated in a reverse-permeabilized human bronchi model
      with CFTR siRNA. After MAG-DHA treatments, messenger RNA transcript levels for
      MUC5AC, IL-6, and IL-8 were markedly reduced in LPS-treated CFTR siRNA bronchi.
      MAG-DHA displays antiinflammatory properties and reduces mucin overexpression in
      Calu-3 cells and human bronchi untreated or treated with P. aeruginosa LPS, a
      finding consistent with the effects of resolvinD1, a known antiinflammatory
      mediator.

PMID- 25781053
TI  - DNA melting and genotoxicity induced by silver nanoparticles and graphene.
AB  - We have revealed a connection between DNA-nanoparticle (NP) binding and in vitro
      DNA damage induced by citrate- and branched polyethylenimine-coated silver
      nanoparticles (c-AgNPs and b-AgNPs) as well as graphene oxide (GO) nanosheets.
      All three types of nanostructures triggered an early onset of DNA melting, where
      the extent of the melting point shift depends upon both the type and
      concentration of the NPs. Specifically, at a DNA/NP weight ratio of 1.1/1, the
      melting temperature of lambda DNA dropped from 94  degrees C down to 76  degrees
      C, 60  degrees C, and room temperature for GO, c-AgNPs and b-AgNPs, respectively.
      Consistently, dynamic light scattering revealed that the largest changes in DNA
      hydrodynamic size were also associated with the binding of b-AgNPs. Upon
      introduction to cells, b-AgNPs also exhibited the highest cytotoxicity, at the
      half-maximal inhibitory (IC50) concentrations of 3.2, 2.9, and 5.2 mg/L for B and
      T-lymphocyte cell lines and primary lymphocytes, compared to the values of 13.4,
      12.2, and 12.5 mg/L for c-AgNPs and 331, 251, and 120 mg/L for GO nanosheets,
      respectively. At cytotoxic concentrations, all NPs elicited elevated
      genotoxicities via the increased number of micronuclei in the lymphocyte cells.
      However, b-AgNPs also induced micronuclei at subtoxic concentrations starting
      from 0.1 mg/L, likely due to their stronger cellular adhesion and
      internalization, as well as their subsequent interference with normal DNA
      synthesis or chromosome segregation during the cell cycle. This study facilitates
      our understanding of the effects of NP chemical composition, surface charge, and
      morphology on DNA stability and genotoxicity, with implications ranging from
      nanotoxicology to nanobiotechnology and nanomedicine. 

PMID- 25781054
TI  - Diverse functions of perlecan in central nervous system cells in vitro.
AB  - Therapeutic treatment targeting one cell type is considered ineffective in
      remedying any injury to the central nervous system (CNS). Perlecan, a multi
      functional, heparan sulfate proteoglycan, shows diverse effects on distinct cell
      types, suggesting that it is one of the candidates that can augment the
      regenerative mechanisms in the injured CNS. Therefore, we examined the functions
      of perlecan in CNS cells in vitro by using perlecan purified from bovine kidney.
      Perlecan-coated cell culture plates, unlike their type I/III collagen-coated
      counterparts, did not inhibit the adhesion of neural stem/progenitor cells
      (NS/PCs) and neurons. The coated perlecan and the perlecan added to the culture
      medium suppressed astrocyte proliferation; however, perlecan added to the medium
      promoted NS/PC proliferation. Neurons were promoted to extend their neurites on
      the perlecan-coated substrate, and perlecan added to the medium also showed a
      similar effect. NS/PC proliferation and neurite extension is a major regenerative
      reaction in CNS injury, whereas excess proliferation of astrocytes cause
      hypertrophy of glial scars, which repels neurons. Our in vitro study suggests
      that perlecan is an attractive candidate to promote regenerative mechanisms and
      to suppress reactions that hamper regenerative processes in cases of CNS injury. 

PMID- 25781055
TI  - Oncological outcome after radical prostatectomy: Marital status does not make a
      difference.
AB  - OBJECTIVES: To examine the impact of marital status on prostate cancer
      characteristics at radical prostatectomy and oncological outcome after surgery at
      a high-volume center. METHODS: We relied on the Martini-Clinic Prostate Cancer
      database and investigated 8088 prostate cancer patients treated with radical
      prostatectomy between January 2000 and March 2011. We analyzed differences in
      clinical and pathological characteristics according to marital status (married
      and partnership vs single). Additionally, we relied on multivariable Cox
      regression analyses to predict biochemical recurrence, metastases and death after
      radical prostatectomy. Finally, Kaplan-Meier analyses were used in a propensity
      score-matched cohort, adjusted for clinical and pathological characteristics, to
      examine differences in biochemical recurrence-free, metastases-free and overall
      survival according to marital status. RESULTS: According to marital status, no
      significant differences were recorded within clinical and pathological
      characteristics (all P > 0.05). The impact of marital status on biochemical
      recurrence (hazard ratio 1.0, 95% confidence interval 0.9-1.3, P = 0.7),
      metastases (hazard ratio 1.3, 95% confidence interval 0.8-2.1, P = 0.3) and death
      (hazard ratio 0.8, 95% confidence interval 0.4-1.6, P = 0.6) after radical
      prostatectomy was not significant (median follow up 48 months). Kaplan-Meier
      analyses recorded no significant differences for biochemical recurrence-free,
      metastases-free and overall survival (all log-rank P > 0.05) according to marital
      status. CONCLUSIONS: Marital status does not affect the clinical and pathological
      characteristics of radical prostatectomy patients treated at a high-volume
      center. Furthermore, marital status does not affect biochemical recurrence-free
      and metastases-free survival after radical prostatectomy.

PMID- 25781056
TI  - Y-chromosomal variation of local goat breeds of Turkey close to the domestication
      centre.
AB  - Genetic variations in chromosome Y are enabling researchers to identify paternal
      lineages, which are informative for introgressions and migrations. In this study,
      the male-specific region markers, sex-determining region-Y (SRY), amelogenin
      (AMELY) and zinc finger (ZFY) were analysed in seven Turkish native goat breeds,
      Angora, Kilis, Hair, Honamli, Norduz, Gurcu and Abaza. A SNP in the ZFY gene
      defined a new haplotype Y2C. All domestic haplogroups originate from Capra
      aegagrus, while the finding of Y1A, Y1B, Y2A and Y2C in 32, 4, 126 and 2 Turkish
      domestic goats, respectively, appears to indicate a predomestic origin of the
      major haplotypes. The occurrence of four haplotypes in the Hair goat and, in
      contrast, a frequency of 96% of Y1A in the Kilis breed illustrate that Y
      chromosomal variants have a more breed-dependent distribution than mitochondrial
      or autosomal DNA. This probably reflects male founder effects, but a role in
      adaptation cannot be excluded.

PMID- 25781057
TI  - Roles of chromatin insulators in the formation of long-range contacts.
AB  - Chromatin insulators are factors involved in higher-order, genome-wide
      organization of chromatin, and play key roles in regulating transcriptional
      programs. In this review, we discuss recent studies on the diverse composition of
      insulator complexes, and on the mechanism by which they establish long-range DNA
      interactions. Particularly, we describe new biophysical methods that allow for
      the study of the composition of large molecular complexes, and for defining the
      factors potentially required to establish long-range DNA contacts. 

PMID- 25781058
TI  - Camptodactyly and knuckle pads coexisting in an adolescent boy: connection or
      coincidence?
AB  - Camptodactyly is a condition characterized by a nontraumatic, fixed flexion
      contracture at the proximal interphalangeal joint, typically involving the fifth
      finger. Most occurrences are sporadic, but autosomal dominant transmission and
      syndromic associations have been described in the literature. We describe the
      case of an adolescent boy who presented to our clinic with a 2-year history of
      bilateral, nonsyndromic camptodactyly and knuckle pads. 

PMID- 25781059
TI  - Management of cancer-associated disseminated intravascular coagulation: guidance
      from the SSC of the ISTH: comment.

PMID- 25781060
TI  - Singlet oxygen phosphorescence lifetime imaging based on a fluorescence lifetime
      imaging microscope.
AB  - The feasibility of singlet oxygen phosphorescence (SOP) lifetime imaging
      microscope was studied on a modified fluorescence lifetime imaging microscope
      (FLIM). SOP results from the infrared radiative transition of O2(a(1)Deltag ->
      X(3)Sigmag(-)) and O2(a(1)Deltag) was produced in a C60 powder sample via
      photosensitization process. To capture the very weak SOP signal, a dichroic
      mirror was placed between the objective and tube lens of the FLIM and used to
      divide the luminescence returning from the sample into two beams: the reflected
      SOP beam and the transmitted photoluminescence of C60 (C60-PL) beam. The C60-PL
      beam entered the scanner of the FLIM and followed the normal optical path of the
      FLIM, while the SOP steered clear of the scanner and directly entered a finely
      designed SOP detection channel. Confocal C60-PL images and nonconfocal SOP images
      were then simultaneously obtained by using laser-scanning mode. Experimental
      results show that (1) under laser-scanning mode, the obstacle to confocal SOP
      imaging is the infrared-incompatible scanner, which can be solved by using an
      infrared-compatible scanner. Confocal SOP imaging is also expected to be realized
      under stage-scanning mode when the laser beam is parked and meanwhile a pinhole
      is added into the SOP detection channel. (2) A great challenge to SOP imaging is
      its extraordinarily long imaging time, and selecting only a few interesting
      points from fluorescence images to measure their SOP time-dependent traces may be
      a correct compromise. 

PMID- 25781061
TI  - Utility of the Cognistat Judgment Subtest in Motorically Impaired Populations.
AB  - The Cognistat is one the most frequently employed measures to briefly evaluate
      cognitive functioning. However, clinical experience indicates that the questions
      within the Judgment subtest may be biased and insensitive toward persons with
      motor impairments. These issues may impact the examinee's performance and
      decrease the validity of the test-not to mention possibly create undue emotional
      distress. Suggestions for rectifying these issues are presented. 

PMID- 25781062
TI  - The association of androgenetic alopecia and insulin resistance is independent of
      hyperandrogenemia: A case-control study.
AB  - BACKGROUND/OBJECTIVES: Androgenetic alopecia (AGA) occurs due to the effect of
      androgens and genetic predisposition. The association between hyperandrogenism
      and insulin resistance (IR) has been clearly documented. In recent years there
      have been reports supporting the presence of IR in AGA. The study aimed to
      investigate the presence of IR in women with AGA and discern whether or not it is
      associated with hyperandrogenism. METHODS: Overall, 77 women with AGA were
      included in the study. Patients with Ludwig grades I-III AGA were enrolled in the
      study. Blood samples were drawn for measurements of hormone profile, basal
      insulin and fasting blood glucose (FBG). An oral glucose tolerance test was
      performed on another day. IR was assessed by the homeostasis model assessment
      score. RESULTS: All IR parameters were significantly higher in the 75 study
      subjects without DM than in the control group (P < 0.05). After excluding five
      patients with IGT, the level of all IR parameters were still higher than in the
      control group (P < 0.05). Hyperandrogenemia was found in 30 (40%) patients. When
      this second group (n = 45) (excluding patients with hyperandrogenemia) was
      compared with the control group on IR, all parameters except for basal insulin
      were significantly higher in the second group than in the controls (P < 0.05).
      CONCLUSION: Our results suggest a relation between IR and AGA in female patients.
      We showed for the first time that the association of AGA and IR is independent of
      hyperandrogenemia.

PMID- 25781063
TI  - Enhanced long-term nitrogen removal and its quantitative molecular mechanism in
      tidal flow constructed wetlands.
AB  - Tidal flow constructed wetlands (TF CWs) have recently been studied as a
      sustainable technology to achieve enhanced nitrogen removal; however, the
      underlying mechanisms responsible for removing ammonium (NH4(+)) and nitrate
      (NO3(-)) have not been compared and quantified at the molecular level (genes) in
      controlled TF CWs. In this study, two TF CWs T1 (treating NH4(+) wastewater) and
      T2 (treating NO3(-) wastewater) achieved high removal efficiencies for chemical
      oxygen demand (COD, 92 +/- 2.7% and 95 +/- 2.4%, respectively), NH4(+)/NO3(-) (76
      +/- 3.9% and 97 +/- 2.2%, respectively), and total nitrogen (TN, 81 +/- 3.5% and
      93 +/- 2.3%, respectively). Combined analyses revealed that the presence of
      simultaneous nitrification, anammox, and denitrification processes and the
      coupling of dissimilatory nitrate reduction to ammonium, ammonia oxidation, and
      anammox were the primary reason accounted for the robust treatment performance in
      T1 and T2, respectively. Results from stepwise regression analysis suggested that
      the NH4(+) removal rate in T1 was collectively controlled by amoA, nxrA, and
      anammox, while the NO3(-) removal rate in T2 was governed by nxrA and narG gene. 

PMID- 25781064
TI  - Influence of pressure and crowding on the sub-nanosecond dynamics of globular
      proteins.
AB  - The influence of high hydrostatic pressure on the internal sub-nanosecond
      dynamics of highly concentrated lysozyme in aqueous solutions was studied by
      elastic incoherent neutron scattering (EINS) up to pressures of 4 kbar. We have
      found, with increasing pressure, a reduction in the dynamics of H atoms of folded
      lysozyme, suggesting a loss in protein mobility that follows a change in the
      local energy landscape upon the increase in packing density. Moreover, the
      amplitude of the protein fluctuations depends drastically on the protein
      concentration, and protein structural and interaction parameters as well as the
      dynamical properties are affected by pressure in a nonlinear way. A significant
      reduction of the mean squared displacement of H atoms occurs already at rather
      low pressures of a few hundred bars for lysozyme in bulk water solution. This
      trend is lifted at ~2 kbar, which is probably due to a solvent-mediated effect.
      Conversely, for high protein concentrations (e.g., 160 mg mL(-1)), that is, under
      strong self-crowding conditions, as they are also encountered in the biological
      cell, strong restriction of the dynamics of protein motions takes place, reducing
      the mean squared displacement of H atoms by 60% and rendering its pressure
      dependence almost negligible. These results are also important for understanding
      the pressure stability of highly concentrated protein solutions in organisms
      thriving under hydrostatic pressure conditions such as in the deep sea, where
      pressures up to the kbar level are reached.

PMID- 25781065
TI  - Novel strategies in the management of polycystic ovary syndrome.
AB  - Polycystic ovary syndrome (PCOS) is a common endocrinopathy affecting
      reproductive-aged women. PCOS has been recognized as a syndrome combining
      reproductive and metabolic abnormalities with lifelong health implications.
      Cardiometabolic alterations require regular screening and effective and targeted
      lifestyle advice to lose weight as well as to prevent weight gain.
      Pharmacological therapy includes insulin-sensitizer drugs and agents that act
      directly on metabolic comorbidities, such as statins and antiobesity drugs.
      Bariatric surgery may be an option for severely obese women with PCOS Regarding
      reproductive aspects, ovulation induction with antiestrogens such as clomiphene
      citrate or letrozole is the first-line medical treatment. Exogenous gonadotropins
      and in vitro fertilization (IVF) are recommended as second-line treatment for
      anovulatory infertility. Laparoscopic ovarian diathermy may be used in special
      cases and metformin is no longer recommended for ovulation induction. Combined
      oral contraceptives (OCs) are the first-line treatment for the management of
      menstrual irregularities in women not seeking pregnancy, also providing
      endometrial protection and contraception. Progestin-only pills or cyclical
      progestins are recommended for those with contraindications to OCs. Metformin is
      also considered a second-line choice for improving menstrual cycles in women
      presenting insulin-resistance and dysglicemia. Hirsutism requires cosmetic
      procedures and medical treatment with OCs. More severe cases may need anti
      androgen drugs added to the OCs. In conclusion, strategies regarding the
      management of reproductive issues in PCOS encompass a tailored approach to
      individual needs of each patient. 

PMID- 25781066
TI  - 5'-beta,gamma-CHF-ATP diastereomers: synthesis and fluorine-mediated selective
      binding by c-Src protein kinase.
AB  - The first preparation of the individual beta,gamma-CHF-ATP stereoisomers 12a and
      12b is reported. Configurationally differing solely by the orientation of the C-F
      fluorine, 12a and 12b have discrete (31)P (202 MHz, pH 10.9, DeltadeltaPalpha 6
      Hz, DeltadeltaPbeta 4 Hz) and (19)F NMR (470 MHz, pH 9.8, DeltadeltaF 25 Hz)
      spectral signatures and exhibit a 6-fold difference in IC50 values for c-Src
      kinase, attributed to a unique interaction of the (S)-fluorine of bound 12b with
      R388 in the active site. 

PMID- 25781067
TI  - Explosion impacts during transport of hazardous cargo: GIS-based characterization
      of overpressure impacts and delineation of flammable zones for ammonia.
AB  - The aim of this research was to investigate accidental releases of ammonia
      followed by an en-route incident in an attempt to further predict the
      consequences of hazardous cargo accidents. The air dispersion model Areal
      Locations of Hazardous Atmospheres (ALOHA) was employed to track the probable
      outcomes of a hazardous material release of a tanker truck under different
      explosion scenarios. The significance of identification of the flammable zones
      was taken into consideration; in case the flammable vapor causes an explosion.
      The impacted areas and the severity of the probable destructions were evaluated
      for an explosion by considering the overpressure waves. ALOHA in conjunction with
      ArcGIS was used to delineate the flammable and overpressure impact zones for
      different scenarios. Based on the results, flammable fumes were formed in oval
      shapes having a chief axis along the wind direction at the time of release. The
      expansions of the impact areas under the overpressure value which can lead to
      property damage for 2 and 20 tons releases, under very stable and unstable
      atmospheric conditions were estimated to be around 1708, 1206; 3742, 3527 feet,
      respectively, toward the wind direction. A sensitivity analysis was done to
      assess the significance of wind speed on the impact zones. The insight provided
      by this study can be utilized by decision makers in transportation of hazardous
      materials as a guide for possible rerouting, rescheduling, or limiting the
      quantity of hazardous cargo to reduce the possible impacts after hazardous cargo
      accidents during transport. 

PMID- 25781068
TI  - Synthesis and photoluminescent properties of geometrically hindered cis
      tris(diphenylaminofluorene) as precursors to light-emitting devices.
AB  - A novel highly luminescent tris-fluorenyl ring-interconnected chromophore
      tris(DPAF-C9) was synthesized using a C3 symmetrical triaminobenzene core as the
      synthon. This structure bears three light-harvesting 2-diphenylamino-9,9
      dialkylfluorenyl (DPAF) ring moieties with each attached by two branched 3',5',5'
      trimethylhexyl (C9) arms. A major stereoisomer was chromatographically isolated
      and characterized to possess a 3D structural configuration of cis-conformer in a
      cup-form. Molecular calculation at B3LYP/6-31G* level revealed the unexpected
      stability of this cis-cup-conformer of tris(DPAF-C9) better than that of the
      stereoisomer in a propeller-form and the trans-conformer. The structural geometry
      is proposed to be capable of minimizing the aggregation related self-quenching
      effect in the condensed phase. Fluorescence emission wavelength of tris(DPAF-C9)
      was found to be in a close range to that of PVK that led to its potential uses as
      the secondary blue hole-transporting material for enhancing the device property
      toward the modulation of PLED performance.

PMID- 25781069
TI  - Potential role of olive oil phenolic compounds in the prevention of
      neurodegenerative diseases.
AB  - Adherence to the Mediterranean Diet (MD) has been associated with a reduced
      incidence of neurodegenerative diseases and better cognitive performance. Virgin
      olive oil, the main source of lipids in the MD, is rich in minor phenolic
      components, particularly hydroxytyrosol (HT). HT potent antioxidant and anti
      inflammatory actions have attracted researchers' attention and may contribute to
      neuroprotective effects credited to MD. In this review HT bioavailability and
      pharmacokinetics are presented prior to discussing health beneficial effects. In
      vitro and in vivo neuroprotective effects together with its multiple mechanisms
      of action are reviewed. Other microconstituents of olive oil are also considered
      due to their potential neuroprotective effects (oleocanthal, triterpenic acids).
      Finally, we discuss the potential role of HT as a therapeutic tool in the
      prevention of neurodegenerative diseases.

PMID- 25781070
TI  - Simultaneous determination of ferulic acid and phthalides of Angelica sinensis
      based on UPLC-Q-TOF/MS.
AB  - The radix of Angelica sinensis (AS) is one of the most commonly used as a herbal
      medicine. To investigate the geoherbalism and quality evaluation of AS, an ultra
      performance liquid chromatography coupled with electrospray ionization quadrupole
      time-of-flight tandem mass spectrometry (UPLC-ESI-Q-TOF/MS) method was
      established to analyze and identify ferulic acid and phthalides in AS. The
      results showed that among samples collected in four regions, the relative
      contents of ferulic acid and phthalides were highest in samples collected in
      Gansu, and the samples from the four different regions were apparently classified
      into four groups. Meanwhile, the relative content in non-fumigated root was
      higher than after sulfur-fumigation and the sulfur-fumigated and non-fumigated
      samples were obviously divided into two groups by PCA. The paper establishes a
      systematic and objective evaluation system to provide a scientific basis for
      evaluating the quality of AS.

PMID- 25781071
TI  - Anti-allergic properties of curine, a bisbenzylisoquinoline alkaloid.
AB  - Curine is a bisbenzylisoquinoline alkaloid isolated from Chondrodendron
      platyphyllum (Menispermaceae). Recent findings have shed light on the actions of
      curine in different models of allergy and inflammation. Here we review the
      properties and mechanisms of action of curine focusing on its anti-allergic
      effects. Curine pre-treatment significantly inhibited the scratching behavior,
      paw edema and systemic anaphylaxis induced by either ovalbumin (OVA) in
      sensitized animals or compound 48/80, through mechanisms of mast cell
      stabilization and inhibition of mast cell activation to generate lipid mediators.
      In addition, oral administration of curine significantly inhibited eosinophil
      recruitment and activation, as well as, OVA-induced airway hyper-responsiveness
      in a mouse model of asthma, through inhibition of the production of IL-13 and
      eotaxin, and of Ca2+ influx. In conclusion, curine exhibit anti-allergic effects
      in models of lung, skin and systemic allergy in the absence of significant
      toxicity, and as such has the potential for anti-allergic drug development.

PMID- 25781072
TI  - Synthesis of peptide nucleic acids containing a crosslinking agent and evaluation
      of their reactivities.
AB  - Peptide nucleic acids (PNAs) are structural mimics of nucleic acids that form
      stable hybrids with DNA and RNA. In addition, PNAs can invade double-stranded
      DNA. Due to these characteristics, PNAs are widely used as biochemical tools, for
      example, in antisense/antigene therapy. Interstrand crosslink formation in
      nucleic acids is one of the strategies for preparing a stable duplex by covalent
      bond formation. In this study, we have synthesized PNAs incorporating 4-amino-6
      oxo-2-vinylpyrimidine (AOVP) as a crosslinking agent and evaluated their
      reactivities for targeting DNA and RNA.

PMID- 25781073
TI  - The Effect of Isolated Hamstrings Fatigue on Landing and Cutting Mechanics.
AB  - The function of the hamstrings in protecting the ACL is not fully understood. The
      purpose of this study was to determine how landing knee mechanics were affected
      by hamstrings fatigue, analyzed with principal components analysis (PCA). Knee
      joint mechanics were collected during single-leg stride landings that were
      followed by lateral and vertical jumps. An isokinetic fatigue protocol was
      employed to reduce hamstrings strength by 75% at the cessation of the exercise
      protocol. On the landing test day, participants performed the stride landing
      maneuvers before and after the fatigue protocol. PCA was performed on the landing
      knee joint angle, moment, and power waveforms, and MANOVAs were conducted on the
      retained PCs of each waveform (P < .05). On the strength test day, hamstrings
      strength recovery was assessed with an identical fatigue protocol followed by
      strength assessment ~75 s after the cessation of exercise. Pre- and postexercise
      hamstrings strength on this day was assessed with a dependent t test (P < .05).
      The hamstrings strength remained significantly reduced by ~8% postexercise (75
      s). For stride landings followed by vertical jumps, there were significantly
      reduced knee flexion angles, extensor moments, and energy absorption. This was
      indicative of a stiffer landing strategy postfatigue, which has been associated
      with increased ACL loading. 

PMID- 25781074
TI  - Synthesis and structure-activity relationships for extended side chain analogues
      of the antitubercular drug (6S)-2-nitro-6-{[4-(trifluoromethoxy)benzyl]oxy}-6,7
      dihydro-5H-imidazo[2,1-b][1,3]oxazine (PA-824).
AB  - Novel extended side chain nitroimidazooxazine analogues featuring diverse linker
      groups between two aryl rings were studied as a potential strategy to improve
      solubility and oral activity against chronic infection by Mycobacterium
      tuberculosis. Both lipophilic and highly polar functionalities (e.g.,
      carboxamide, alkylamine, piperazine, piperidine, but not sulfonamide) were well
      tolerated in vitro, and the hydrophilic linkers provided some solubility
      improvements, particularly in combination with pyridine rings. Most of the 18
      compounds further assessed showed high microsomal stabilities, although in the
      acute infection mouse model, just one stilbene (6-fold) and two pyridine
      containing acetylene derivatives (5-fold and >933-fold) gave in vivo efficacies
      notably superior to the clinical stage compound pretomanid (PA-824). The most
      efficacious analogue also displayed outstanding in vivo activity in the stringent
      chronic model (up to 24-fold better than the drug delamanid and 4-fold greater
      than our previous best phenylpyridine candidate), with favorable
      pharmacokinetics, including good oral bioavailability in the rat. 

PMID- 25781075
TI  - Investigation on the conductivity-dependent performance in low voltage
      cathodoluminescence.
AB  - With the increase of applied current density in low voltage cathodoluminescence,
      the exciting power tends to saturate, causing the saturation of electron-hole
      generation rate in the phosphor layer. Moreover, ground-state depletion could
      emerge for the activators owing to the increased exciting power and decreased
      average penetration depth of incident electrons in the phosphor layer, causing
      the decrease of the energy transfer probability of e-h pairs exciting ground
      state activators. In addition, the radiative transition probability of excited
      activators could be decreased due to the increase of temperature. In view of
      these key factors, the efficiency decrease in cathodoluminescence is the
      inevitable result. To restrain the efficiency decrease so as to improve the
      performance in low voltage cathodoluminescence, the conductivity of the phosphor
      material was improved. By introducing a conductive component, which improves the
      conductivity of the phosphor material, the performance in low voltage
      cathodoluminescence was effectively improved. 

PMID- 25781076
TI  - Protection from neurodegeneration in the 6-hydroxydopamine (6-OHDA) model of
      Parkinson's with novel 1-hydroxypyridin-2-one metal chelators.
AB  - Brain iron accumulation has been associated with inciting the generation of
      oxidative stress in a host of chronic neurological diseases, including
      Parkinson's disease. Using the catecholaminergic neurotoxin 6-hydroxydopamine to
      lesion cellular dopaminergic pathways as a model of Parkinson's disease in
      culture, a selection of 1-hydroxypyridin-2-one (1,2-HOPO) metal chelators were
      synthesized and their neuroprotective properties were compared to the 3
      hydroxypyridin-4-one; deferiprone (3,4-HOPO; DFP). Protection against 6-OHDA and
      iron insult by the novel compounds 6 and 9 was comparable to DFP. Iron associated
      changes by 6-OHDA imply that the neuroprotective capacity of these compounds are
      due to chelation of the neuronal labile iron pool and the requirement of the iron
      binding moiety of compound 6 for efficacy supported this hypothesis. In
      conclusion, two novel 1,2-HOPO's and DFP have comparable neuroprotection against
      Parkinsonian-associated neurotoxins and supports the continued development of
      hydroxypyridinone compounds as a non-toxic therapeutic agent in the treatment of
      neurodegenerative disease.

PMID- 25781077
TI  - Education in Disaster Management and Emergencies: Defining a New European Course.
AB  - OBJECTIVE: Unremitting natural disasters, deliberate threats, pandemics, and
      humanitarian suffering resulting from conflict situations necessitate swift and
      effective response paradigms. The European Union's (EU) increasing visibility as
      a disaster response enterprise suggests the need not only for financial
      contribution but also for instituting a coherent disaster response approach and
      management structure. The DITAC (Disaster Training Curriculum) project identified
      deficiencies in current responder training approaches and analyzed the
      characteristics and content required for a new, standardized European course in
      disaster management and emergencies. METHODS: Over 35 experts from within and
      outside the EU representing various organizations and specialties involved in
      disaster management composed the DITAC Consortium. These experts were also
      organized into 5 specifically tasked working groups. Extensive literature reviews
      were conducted to identify requirements and deficiencies and to craft a new
      training concept based on research trends and lessons learned. A pilot course and
      program dissemination plan was also developed. RESULTS: The lack of
      standardization was repeatedly highlighted as a serious deficiency in current
      disaster training methods, along with gaps in the command, control, and
      communication levels. A blended and competency-based teaching approach using
      exercises combined with lectures was recommended to improve intercultural and
      interdisciplinary integration. CONCLUSION: The goal of a European disaster
      management course should be to standardize and enhance intercultural and inter
      agency performance across the disaster management cycle. A set of minimal
      standards and evaluation metrics can be achieved through consensus, education,
      and training in different units. The core of the training initiative will be a
      unit that presents a realistic situation "scenario-based training."

PMID- 25781078
TI  - Does left-handedness confer resistance to spatial bias?
AB  - We recently demonstrated that drowsiness, indexed using EEG, was associated with
      left-inattention in a group of 26 healthy right-handers. This has been linked to
      alertness-related modulation of spatial bias in left neglect patients and the
      greater persistence of left, compared with right, neglect following injury.
      Despite handedness being among the most overt aspects of human lateralization,
      studies of this healthy analogue of left neglect have only been conducted with
      predominantly or exclusively right-handed individuals. Here, with a group of 26
      healthy non-right-handers we demonstrate that, unlike right-handers who showed a
      rightward shift in attention with drowsiness, non-right-handers showed the
      opposite pattern on an auditory spatial localization task. The current results
      are the first indication that factors linked to handedness can affect the
      development and extremity of spatial biases, potentially conferring resilience to
      clinical symptoms in non-right-handers and, given that 90% of us are right
      handed, why left neglect is disproportionately persistent. 

PMID- 25781080
TI  - Taxonomic review of the species of Mugil (Teleostei: Perciformes: Mugilidae) from
      the Atlantic South Caribbean and South America, with integration of
      morphological, cytogenetic and molecular data.
AB  - Analysis of morphological, molecular and cytological data helped to define and
      more precisely characterize the species of Mugil from the Atlantic coasts of
      South Caribbean and South America, allowing a correction of prior
      misidentifications and distributional ranges. A new species from Venezuela is
      described and all the species from the area are redescribed. It is demonstrated
      that the apparent similarity in morphological traits, which contradicted the
      results from recent molecular studies, is the result of the misuse of traditional
      morphological characters, and thus both the molecular and cytological data
      instead are congruent with the morphological differences that are found among
      mullet species. The presence of Mugil hospes Jordan & Culver in the western south
      Atlantic is refuted based on the comparison of type material of this species with
      specimens from this area that also indicated a very significant morphological
      difference, what on the other hand justifies the recognition of these specimens
      as Mugil brevirostris (Ribeiro). The distribution of Mugil incilis Hancock is
      restricted and the similarities among the species formerly depicted in a prior
      dendrogram is modified following the inclusion of recently obtained molecular
      data for Mugil curvidens Valenciennes. 

PMID- 25781081
TI  - Adaptive morpho-traits, taxonomy and biogeography of Metania Gray, 1867
      (Porifera: Spongillina: Metaniidae) with the description of a new species from
      Madagascar.
AB  - A comparative analysis of gemmular architecture adaptive morpho-traits at family
      level is reported for Metaniidae together with the discovery and description of a
      new species from the River Mangoky (High Plateau), Madagascar. The new Malagasy
      species, ascribed to Metania for diagnostic traits of the skeleton and the
      gemmular architecture, differs from all the other known species of the genus in
      its unique combination of diagnostic traits. Metania madagascariensis sp. nov. is
      characterised by encrusting growth form, conulose surface, specialized ectosomal
      skeleton, alveolate-reticulate choanosomal skeleton, two types of megascleres as
      smooth oxeas (alpha) and acanthoxeas (beta) ornamented with spines and/or
      tubercles, one type of microsclere as acanthoxeas with dense spines/tubercles
      bearing rosettes of microspines at tips; gemmules with or without cage of
      megascleres and frequently surrounded by microscleres; gemmular theca trilayered
      with pneumatic layer of fibrous spongin, boletiform (trumpet-like) gemmuloscleres
      with proximal true rotule large, smooth and with irregular blunt margins, and
      distal knob-like pseudorotule notably smaller, with a few hooks at the margins.
      M. madagascariensis belongs to the Afrotropical species group of Metania.
      Identification keys and an annotated checklist at global level are also provided
      together with a species-level discussion of Metania focusing on morphology,
      taxonomy, nomenclature and biogeography. 

PMID- 25781082
TI  - A revision of the Anthaxia (Haplanthaxia) schah Abeille de Perrin, 1904 species
      group, with description of two new species from Iran (Coleoptera: Buprestidae:
      Anthaxiini).
AB  - Two new species of Anthaxia Eschscholtz, 1829 endemic to Iran, Anthaxia
      (Haplanthaxia) cadusiana sp. nov. and A. (H.) elamita sp. nov., are described and
      compared to their most similar species. The A. (H.) schah Abeille de Perrin, 1904
      species-group is proposed and revised, and lectotypes for A. (H.) schah Abeille
      de Perrin, 1904 and A. (H.) wethloi Obenberger, 1940 are designated. All species
      of the new species-group are illustrated, including type specimens. A short
      definition of the new species-group and a key to its species are given, together
      with data on the distribution, bionomy and taxonomic position for each of the
      species that compose it. 

PMID- 25781083
TI  - Abalakeus Southcott, 1994 is a junior synonym of "plume-footed" Eatoniana
      Cambridge, 1898 (Trombidiformes, Erythraeidae)--evidence from experimental
      rearing.
AB  - Eatoniana Cambridge, 1898 was previously known exclusively from active postlarval
      forms. In the course of experimental rearing, larvae showing a strong affinity to
      members of Abalakeus jahromiensis Sedghi, Saboori et Hakimitabar, 2010, were
      obtained from a field-collected female of Eatoniana plumipes (L. Koch, 1856).
      Studies of all members of Abalakeus compared with newly obtained larvae of
      Eatoniana, resulted in synonymisation of Abalakeus Southcott, 1994 with Eatoniana
      and of A. jahromiensis with E. plumipes. Complementary data to the previous
      diagnosis of Eatoniana and information on the biology of E. plumipes are
      provided. A female of E. plumipes was selected as the neotype. A key to Eatoniana
      spp. known from larvae is provided. 

PMID- 25781084
TI  - Korean species of the genus Neoperla Needham, 1905 (Plecoptera: Perlidae).
AB  - Two new species of the perlid genus Neoperla, N. adamantea Muranyi & Li, sp. n.
      and N. goguryeo Muranyi & Li, sp. n. are described from both sexes, collected in
      the Kumgang and Myohyang Mountains of North Korea by personnel of the Hungarian
      Natural History Museum during the 1970's. Two additional species, N. coreensis
      Ra, Kim, Kang & Ham, 1994 and N. ussurica Sivec & Zhiltzova, 1996 are redescribed
      from North Korean specimens. Neoperla quadrata Wu & Claassen, 1934 is redescribed
      on the basis of the holotype from Sichuan Province, China, and the Korean
      occurrence of this species requires confirmation. Korean and global distributions
      of the five Neoperla species reported from the peninsula are depicted on maps. 

PMID- 25781085
TI  - Three new species of the family Phthiracaridae (Acari, Oribatida) from Bolivia.
AB  - Three new species of the family Phthiracaridae, Austrophthiracarus longisetosus
      sp. nov., Phthiracarus allocotos sp. nov., Protophthiracarus amboroensis sp. nov.
      from Bolivia are described and figured. A comparison of morphological
      similarities with the most closely related species is presented. Additional
      descriptions and taxonomical notes for three ptyctimous species: Acrotritia
      peruensis (Hammer, 1961), Acrotritia vestita (Berlese, 1913), and Steganacarus
      (Rhacaplacarus) sedecimus Niedbala, 2004 are added. A list of twenty six
      ptyctimous species from Bolivia is presented, ten of these species are new
      records for the fauna of Bolivia. A key to all species of ptyctimous mites of
      Bolivia is presented. 

PMID- 25781086
TI  - Crabs of the families Palicidae and Crossotonotidae (Crustacea, Decapoda,
      Brachyura, Palicoidea) from the Ogasawara Islands, Japan, with the description of
      a new species.
AB  - Four species of palicoid crabs, Neopalicus jukesii (White, 1847) and Rectopalicus
      ampullatus Castro, 2000 of the family Palicidae, and Crossotonotus spinipes (De
      Man, 1888) and a new species of Pleurophricus A. Milne-Edwards, 1873 of the
      family Crossotonotidae, are recorded from the Ogasawara Islands, Japan.
      Diagnostics for the new species are the protruded bilobed front, six subacute
      lobate teeth at each lateral margin of the carapace, six rounded lobes at the
      posterior margin of the carapace, a crested armature of the cheliped carpus, and
      the strongly depressed ambulatory legs, which readily distinguish it from its two
      congeners, P. cristatipes A. Milne-Edwards, 1873 known by two males from
      Australia and the Kai Islands in Indonesia, and P. longirostris (Moosa & Serene,
      1981) known by a female from the Sunda Strait, Indonesia. 

PMID- 25781087
TI  - Review of the genus Mansonella Faust, 1929 sensu lato (Nematoda: Onchocercidae),
      with descriptions of a new subgenus and a new subspecies.
AB  - Based on material deposited in museum collections, twelve species within
      Mansonella sensu lato were examined and their descriptions amended. Based on
      additional morphological details, the erection of the new monotypic subgenus
      Filyamagutia Bain & Uni for M. (F.) akitensis (Uni, 1983), and the new
      combination M. (Pseudolitomosa) musasabi (Yamaguti, 1941) Bain & Uni are
      proposed. A new subspecies, M. (Tetrapetalonema) atelensis amazonae Bain &
      Guerrero is described and a key to the seven subgenera of Mansonella is provided.
      Furthermore, the elevation of Sandnema to full genus rank comprising the two
      species S. digitatum (Chandler, 1929) n. comb. and S. sunci (Sandground, 1933) n.
      comb., is proposed. Host and geographic records for the species of Mansonella and
      Sandnema are included. 

PMID- 25781088
TI  - A new East-Asian species in the Chrysoperla carnea-group of cryptic lacewing
      species (Neuroptera: Chrysopidae) based on distinct larval morphology and a
      unique courtship song.
AB  - Larval morphology and substrate-borne vibrational courtship songs have been
      hypothesized to distinguish and isolate Chrysoperla 'nipponensis-B' from true
      'Type A' Chrysoperla nipponensis (Okamoto), both of which occur sympatrically in
      eastern Asia. Here, we formally describe C. 'nipponensis-B' as Chrysoperla
      nigrocapitata sp.n., based on populations sampled throughout Japan and at two
      sites in South Korea. Behavioral playback experiments show that males and females
      of each species reject the duetting songs of non-conspecifics, supporting the
      existence in nature of strong premating reproductive isolation between the two
      species. Detailed morphological analysis substantiates that the adults of the two
      species are nearly identical. However, the dorsum of the larval head of C.
      nigrocapitata is usually darkly and heavily pigmented, in striking contrast to
      the condition seen in C. nipponensis; if available, it is probably the best trait
      for distinguishing the two species morphologically. Other aspects of life
      history, ecology, geographic distribution, and molecular systematics of the new
      species are briefly considered. 

PMID- 25781089
TI  - Elucidating taxonomic problems of the genus Disparia Nagano, 1916 of Taiwan and
      its neighboring areas, with description of one new species (Lepidoptera,
      Notodontidae).
AB  - The taxonomic problems of the genus Disparia Nagano, 1916 in Taiwan and its
      neighboring areas are elucidated in the present study. The hitherto well-known
      separated taxonomic units, Fentonia nigrofasciata Wileman, 1910 and
      Pseudofentonia medioalbida Nakamura, 1973, are confirmed as the conspecific
      species based on the type material examination. The latter is here treated as a
      junior synonym (syn. nov.). The taxon previously identified as "D. nigrofasciata"
      in most of studies is actually D. wilemani Matsumura, 1925 stat. rev. Fentonia
      variegata Wileman, 1910 is retained for the eastern Asian population as a
      subspecies of widespread D. diluta (Wileman, 1910) through comparison with other
      populations. In addition, one new species, D. kobayashii sp. nov., endemic to
      Taiwan is described. Including D. maculata (Moore, 1879), totally five Disparia
      species are distributed in Taiwan. 

PMID- 25781090
TI  - A new species of the hermit crab genus Pagurus Fabricius, 1775 (Crustacea:
      Decapoda: Anomura: Paguridae) from shallow coastal waters in Japan, with a
      checklist of the East Asian species of the genus.
AB  - A new species of hermit crab of the family Paguridae, Pagurus rectidactylus, is
      described and illustrated on the basis of material from inshore waters in the
      Seto Inland Sea and the Sea of Japan. It appears closest to P. quinquelineatus
      Komai, 2003, also known from Japan, but is easily distinguished from the latter
      by the dactylus of the right cheliped almost unarmed or armed only with a few
      tiny spines or tubercles, instead of dorsal and dorsomesial rows of conspicuous
      spines, and the more elongate and slender ambulatory legs with more numerous
      ventral corneous spines on dactyli and propodi. Housing is also different between
      the two species: the new species exclusively inhabits carcinoecia formed by a
      hydrozoan Stylactaria misakiensis (Iwasa, 1934), whereas P. quinquelineatus uses
      gastropod shells without association with coelenterates. A checklist of East
      Asian (Japanese Archipelago to Taiwan Island, Far Eastern Russia to northern
      China) species of Pagurus along with general geographical distributions is
      presented. 

PMID- 25781091
TI  - A new genus of bamboo coral (Octocorallia: Isididae) from the Bahamas.
AB  - A bamboo coral collected during a deep-sea expedition to the Bahamas in 2009
      proved to have a unique combination of features for a member of the bamboo coral
      subfamily Keratoisidinae: the structure and shape of the polyps, the sclerites
      consisting entirely of rods, some of which extend the length of the polyp, the
      delicateness of the branches with solid internodes, and the deep funnel
      construction of the peristomal region into which the tentacles can contract. The
      specimens are described as a new genus and species. 

PMID- 25781092
TI  - A new genus and new species of Paguridae (Crustacea: Decapoda: Anomura) from
      shallow subtidal waters in Okinawa Island, the Ryukyu Islands, Japan.
AB  - During a survey on decapod crustacean fauna of shallow coral reefs and nearby
      environments in Okinawa Island, Ryukyu Archipelago, Japan, four specimens of a
      small but distinctive undescribed species of pagurid hermit crab, which could not
      be referred to any known genus, were collected. The new taxon, Eutrichopagurus
      shirakawai n. gen., n. sp., is described and illustrated herein. The new genus is
      characterized by the possession of 11 pairs of deeply quadriserial
      phyllobranchiate gills, the third maxilliped with well-developed crista dentata
      and one or two accessory teeth on the ischium, the presence of unpaired left
      gonopore in the female, the absence of paired first pleopods in the female, and
      the telson with prominent tuft of setae on the lateral margin of the posterior
      lobes; the male is unknown at present. It appears close to Trichopagurus de Saint
      Laurent, 1968, but the deeply quadriserial gills immediately distinguish
      Eutrichopagurus from Trichopagurus. The new genus is also compared with other
      genera characterized by the possession of 11 pairs of quadriserial
      phyllobranchiate gills and the lack of paired first pleopods in females. 

PMID- 25781093
TI  - A new species of Samba s. str. (Hymenoptera: Melittidae) from the Turkana Basin,
      Kenya with observations on the function of the metatibial spur in females.
AB  - The third known species of the Afrotropical subgenus Samba s. str. is described
      based upon eight females. This is the northernmost and also the most arid habitat
      record for the genus. Images are provided of the habitus and diagnostic features
      for the species as well as the subgenus and some notes on floral hosts and
      habitat are provided. The species is added to a morphology-based phylogeny for
      the genus and results of barcoding of some species of the genus are presented.
      Some unusual morphological features of the subgenus are discussed, in particular,
      the function of the remarkable metatibial spurs of the female is recorded as
      assisting with removal of pollen from a floral host. 

PMID- 25781094
TI  - Two new freshwater eutardigrade species from Sicily.
AB  - Two new species of freshwater Eutardigrada are described from Sicily:
      Isohypsibius rusticus sp. nov. and Isohypsibius zappalai sp. nov. The former
      species has eye spots, ornamented body surface with many, variously sized
      tubercles; bucco-pharyngeal apparatus of the Isohypsibius type; pharyngeal bulb
      with apophyses and two rod-shaped macroplacoids; microplacoid absent; claws, of
      the Isohypsibius type, well developed, with long and thin common basal portion;
      main branches of all claws without free accessory points; very thin lunules
      present; cuticular bars on the legs absent. Isohypsibius zappalai sp. nov. has
      eye spots; entire body surface with small tubercles rounded in shape, fairly
      uniformly sized and tending to form transverse lines; bucco-pharyngeal apparatus
      of the Isohypsibius type, pharyngeal bulb with apophyses and two macroplacoids;
      microplacoid absent; claws of the Isohypsibius type, well developed, with long
      common basal portion and both main and secondary branches with a wide proximal
      portion. Main branches of all claws with accessory points; small, flexible
      lunules present; cuticular bars on the legs absent.

PMID- 25781095
TI  - Two closely related Homidia species (Entomobryidae, Collembola) revealed by
      morphological and molecular evidence.
AB  - Two closely related Homidia species, H. fascia Wang & Chen, 2001 and H.
      pseudofascia sp. nov., are recognized by both morphological and molecular
      approaches. Both species have minor morphological differences except distinct
      colour patterns on thorax. Genetic distances (18%) of COI barcodes between them
      greatly exceed commonly employed threshold (3%), also indicating two independent
      species. The use of colour pattern in taxonomy of Homidia is also discussed. 

PMID- 25781096
TI  - Caetetermes taquarussu Fontes (Isoptera, Termitidae, Nasutitermitinae):
      description of the imago caste and new distributional records.

PMID- 25781097
TI  - Redescriptions of Hypogastruridae and Onychiuridae (Collembola) described by
      David L. Wray.
AB  - Species of Hypogastruridae and Onychiuridae described by D. L. Wray were
      reexamined and redescribed where necessary from type material and other
      specimens. Mitchellania hermosa is redescribed and transferred to Ceratophysella.
      Hypogastrura ireneae is redescribed and H. gravesi is validated with additional
      material. Hypogastrura gami is synonymized with H. humi and H. utahensis is
      synonymized with H. promatro. A lectotype is designated for Schoettella
      (Knowltonella) idahoensis. Achorutes magnoliana is confirmed as a synonym of
      Schoettella glasgowi. Xenylla carolinensis is synonymized with Xenyllodes armatus
      Axelson (Odontellidae). Onychiurus mai is transferred to the genus Leeonychiurus
      and becomes L. mai, and O. magninus is transferred to Heteraphorura and becomes
      H. magnina. Additional details are given for Onychiurus wilchi. 

PMID- 25781098
TI  - A checklist of the aspidogastrea (platyhelminthes: trematoda) of the world.
AB  - A checklist of records of aspidogastrean trematodes (Aspidogastrea) is provided
      on the basis of a comprehensive survey of the literature since 1826, when the
      first aspidogastrean species was reported, until December 2014. We list 61
      species representing 13 genera within 4 families and 2 orders of aspidogastreans
      associated with 298 species of invertebrate and vertebrate hosts. The majority of
      records include bivalves (44% of the total number of host-parasite associations),
      whereas records from bony fishes represent 32% of host-parasite associations. The
      aspidogastreans have worldwide distribution, with the highest number of records
      in the Neartic Region for freshwater hosts and the North Atlantic Ocean for
      marine ones. The checklist includes a parasite-host list with data on host
      habitat, site of infection and distribution area of parasites, and a host
      parasite list. A limited number of molecular studies on aspidogastreans does not
      allow us to unravel phylogenetic relationships within the Aspidogastrea. 

PMID- 25781099
TI  - A new species of Rhadinella (Serpentes: Colubridae) from the Pacific versant of
      Oaxaca, Mexico.
AB  - I describe a new species of Rhadinella from the Pacific versant of Oaxaca,
      Mexico, a region where the genus was previously unknown. This diminutive snake is
      a member of a group of snakes that have dark dorsal coloration, which mostly or
      completely obfuscates a pattern of longitudinal striping characteristic of most
      species of Rhadinella. The closest relative of the new species, on the basis of
      morphological similarities, appears to be Rhadinella pilonaorum which occurs to
      the east of the Isthmus of Tehuantepec about 800 km from the type-locality of the
      new species. 

PMID- 25781100
TI  - A catalogue of the types of Stratiomyidae (Diptera: Brachycera) in the collection
      of the Museu de Zoologia da Universidade de Sao Paulo, Brazil.
AB  - Following a recommendation of the International Code of Zoological Nomenclature,
      a catalogue of the type specimens of Stratiomyidae (Diptera: Brachycera) held in
      the collection of the Museu de Zoologia da Universidade de Sao Paulo, Brazil
      (MZUSP) is provided, with information on 30 type specimens (including 14 primary
      types) of 17 Neotropical species. 

PMID- 25781101
TI  - Contribution to the knowledge of the genus Syndicus Motschulsky (Coleoptera:
      Staphylinidae: Scydmaeninae) in China.
AB  - Two new species of the ant-like stone beetle genus Syndicus Motschulsky
      (Scydmaeninae: Cyrtoscydmini) from the Hainan Island, southern China are
      described: S. (Semisyndicus) grossepunctatus sp. n. and S. (Semisyndicus)
      hainanicus sp. n. The previously unknown female of S. (Semisyndicus) schuelkei is
      discovered, and its spermatheca is illustrated. Syndicus (s. str.) jaloszynskii
      is newly recorded from Hunan, central China. A single female of the nominotypical
      subgenus from Motuo, Xizang is listed; its identity remains unconfirmed until
      associated males become available. 

PMID- 25781102
TI  - Palaearctic species of the Hercostomus plagiatus group (Diptera: Dolichopodidae)
      with description of a new species from the Middle East.
AB  - The Hercostomus plagiatus species group is defined and distinguished from other
      Hercostomus groups by the following combination of features including: bulging
      clypeus in both sexes, anterodorsal comb-like row of setae on fore tibia, usually
      straight and weakly convergent veins R4+5 and M1+2, hypopygium without
      basiventral epandrial lobes, mostly free hypandrium, relatively poorly developed
      postgonite, and female terminalia with tergite 8 and sternite 8 fused
      anterolaterally forming a narrow process. A new species, Hercostomus golanensis
      sp. nov., is described from the Middle East (Golan Heights), differing from the
      other species of this group in the long-pubescent arista-like stylus, triangular
      rather than oval male cercus and epandrial lobe bearing a very long seta at the
      base of the stem. A key to species of the H. plagiatus group is provided.

PMID- 25781103
TI  - First record of the genus Anaxiphomorpha Gorochov (Orthoptera: Gryllidae) from
      China, with description of four new species.
AB  - The genus Anaxiphomorpha Gorochov, 1987 is recorded to China for the first time.
      We provide supplementary characters of female for generic diagnosis. Four new
      species from China are described and illustrated, Anaxiphomorpha
      serratiprotuberus sp. nov. A. brevisparamerus sp. nov. A. biserratus sp. nov. and
      A. longiserratus sp. nov. A key and a distribution map of all species in the
      world are presented. 

PMID- 25781104
TI  - A new species and two new records of the family Phytoseiidae (Acari:
      Mesostigmata) from Turkey.
AB  - Phytoseius ibrahimi Doker & Kazak sp. nov. is described and illustrated. The
      genus Paragigagnathus Amitai & Grinberg, represented by P. insuetus (Livshitz &
      Kuznetsov), and Neoseiulus neomarginatus Stathakis, Kapaxidi & Papadoulis, are
      recorded from Turkey for the first time. Identification keys for the Turkish
      species of Phytoseius Ribaga and Neoseiulus Hughes are provided. 

PMID- 25781105
TI  - Two new species of the genus Arboridia Zachvatkin (Hemiptera: Auchenorrhyncha:
      Cicadellidae: Typhlocybinae) from Korea.
AB  - Two new species of the genus Arboridia Zachvatkin, A. koreana sp. nov., A.
      septempunctata sp. nov., are described from Korea. Photographs of dorsal habitus,
      illustrations of male genitalia, abdomens and forewings, and biological
      information such as host plants and distributional records and a key to the
      Korean Arboridia species are provided. 

PMID- 25781106
TI  - Taxonomic study of the leafhopper genus Thagria Melichar (Hemiptera:
      Cicadellidae: Coelidiinae) from Guangxi, China.
AB  - The paper deals with 21 valid species of the genus Thagria from Guangxi
      Autonomous Region, China. Eight new species are described and illustrated: T.
      biprocessa Fan & Dai, sp. nov., T. decussata Fan & Dai, sp. nov., T. irregularis
      Fan & Dai, sp. nov., T. multispinosa Fan & Dai, sp. nov., T. paramultipars Fan &
      Li, sp. nov., T. triangula Fan & Li, sp. nov., T. trifasciata Fan & Li, sp. nov.
      and T. webbi Fan & Li, sp. nov.. A key is given to distinguish all species of
      this genus from Guangxi, China and maps showing the geographic distribution of
      new species are also provided. The name Thagria xuae nom. emend. is given for T.
      xui Nielson. 

PMID- 25781107
TI  - Species of Thripinae (Thysanoptera) from bamboo in Malaysia, with one new species
      and six new records.
AB  - Nine species of Thripinae that inhabit bamboo are recorded from Malaysia.
      Clypeothrips idrisi sp.n. is described as a second species in the genus, and
      Trichromothrips bruncurrum Reyes is considered a syn.n. of Neocorynothrips
      asiaticus Ramakrishna & Margabandhu. Six species are newly recorded from
      Malaysia: N. asiaticus, Okajimaella tubercula, Simulothrips banpoti,
      Stenchaetothrips bambusicola, S. bambusae and S. spinalis. Seven species of
      Stenchaetothrips are now known from Malaysia. Illustrations and descriptions of
      each species are provided. 

PMID- 25781108
TI  - Disentangling a taxonomic nightmare: a revision of the Australian, Indomalayan
      and Pacific species of Altica Geoffroy, 1762 (Coleoptera: Chrysomelidae:
      Galerucinae).
AB  - The genus Altica Geoffroy, 1762, is revised for Australia, the west Pacific
      region and the Indomalayan Archipelago, with 6 valid species: A. aenea (Olivier,
      1808); A. birmanensis (Jacoby, 1896); A. caerulea (Olivier, 1791); A. corrusca
      (Erichson, 1842); A. cyanea Weber, 1801; A. gravida (Blackburn, 1896). The
      following new synonymy is recognised, in original combinations, senior synonym
      first: Galeruca aenea Olivier = Haltica ignea Blackburn, 1889, syn. nov., =
      Haltica bicolora Jacoby, 1904, syn. nov., = Altica jussiaeae Gressitt, 1955, syn.
      nov.; Galeruca caerulea Olivier = Haltica elongata Jacoby, 1884, syn. nov., =
      Altica brevicosta Weise, 1922; Haltica corrusca Erichson = Haltica pagana
      Blackburn, 1896, syn. nov.; Haltica birmanensis Jacoby = Haltica indica Shukla,
      1960, syn. nov. Altica brevicosta and A. birmanensis are removed from synonymy
      with A. cyanea and A. indica is removed from synonymy with A. caerulea. The
      Altica caerulea of Maulik and subsequent authors (not Olivier) is a
      misidentification of two species, correctly named A. cyanea and A. birmanensis.
      The Altica cyanea of Maulik and subsequent authors (not Weber) is a
      misidentification, correctly named A. aenea. Altica bicosta Shukla, 1960, is
      removed from synonymy with A. brevicosta and regarded as a valid species. Altica
      splendida Olivier, 1808, and Haltica ferruginis Blackburn, 1889, are transferred
      to Sutrea Baly, 1876, as S. splendida (comb. nov.) and S. ferruginis (comb.
      nov.). The type species of Sutrea is designated as S. elegans Baly, 1876. Altica
      albicornis Medvedev, 2004, is transferred to Phygasia Dejean, 1836, as P.
      albicornis (comb. nov.). Lectotypes are designated for A. australis, A.
      birmanensis, A. caerulea, A. cyanea, A. elongata, A. ignea and A. pagana. A
      neotype is designated for A. aenea. Altica caerulea is newly recorded from
      Australia and A. cyanea is removed from the Australian fauna. Altica corrusca and
      A. gravida are endemic to Australia; all published records of these species from
      outside Australia refer to the widespread Asian-Pacific species A. aenea. The
      single record of the European Altica oleracea (L., 1758) from New Caledonia is
      regarded as a label error and this species removed from the Pacific fauna. A key,
      based primarily on genitalic structures, is provided for the six regional species
      and all are redescribed. Host plant records are reviewed: A. corrusca is a minor
      agricultural pest; A. aenea, A. caerulea and A. cyanea may be useful for
      biocontrol of weeds. 

PMID- 25781109
TI  - Persanura hyrcanica, a new genus and species of Neanurinae (Collembola:
      Neanuridae) from Iran, with a key to genera of the tribe Neanurini.
AB  - Persanura hyrcanica, a new genus and species of Neanurini from Iran is described
      and illustrated. It has a unique suite of morphological characters: labrum with
      only 4 chaetae, fusion of tubercles So and L on head, tubercle Di on th. II-III
      with 2 chaetae and separation of tubercles Di on abd. V. The erected genus is
      closely related to Neanura MacGillivray, 1893, Kalanura Smolis, 2007 and Xylanura
      Smolis, 2011. An updated key to genera of the tribe Neanurini is given. 

PMID- 25781110
TI  - Three new species of Exampithoe from Australia and New Zealand (Ampithoidae:
      Amphipoda: Crustacea).
AB  - Three new species of Exampithoe are described from Australia and New Zealand.
      Material described here corroborates the peculiar mandibular palp variability,
      with either a two- or three- articulate palp reported for species within the
      genus Exampithoe compared to the absence of the mandibular palp in Melanesius.
      The Exampthoinae remain a Southern Hemisphere subfamily with nine described
      species. 

PMID- 25781111
TI  - Two new species of the acifer species group of Polypedilum subgenus Tripodura
      Townes from China (Diptera: Chironomidae).
AB  - Polypedilum (Tripodura) falcatum sp. n. and P. (T.) procerum sp. n. of the acifer
      species group of Polypedilum subgenus Tripodura Townes are described and
      illustrated as male imagines from China. The male adult of P. (T.) falcatum sp.
      n. is distinguished by the presence of two faint markings on wing; short and
      interrupted abdominal tergite bands; the sickle-like superior volsella bearing 0
      2 outer setae and a tuft of short setae on its apex. The male adult of P. (T.)
      procerum sp. n. differs in having short abdominal tergite bands; a long, slender
      and apically curved superior volsella; a high fore leg ratio (2.30-2.33). A key
      to known male imagines of Polypedilum subgenus Tripodura from China is presented.

PMID- 25781112
TI  - The type specimens, type localities and nomenclature of Sarcoramphus vultures
      (Aves: Cathartidae), with a note on their speciation.
AB  - A nomenclatural review of Sarcoramphus vultures resulted in the following: The
      genus Sarcoramphus was described by Dumeril in 1805 rather than 1806. Vultur papa
      Linnaeus, 1758, is the type of Sarcoramphus by subsequent monotypy (Froriep in
      Dumeril 1806), not by Vigors's (1825) designation. The type of the genus Gypagus
      Vieillot, 1816, is, by monotypy, Vultur gryphus Linnaeus, 1758, not Vultur papa
      Linnaeus, 1758. Due to this, Gypagus is a junior objective synonym of Vultur
      Linnaeus, 1758. Gyparchus was created by Gloger (1841) as a new genus for Vultur
      papa Linnaeus, 1758, not as an emendation of Gypagus Vieillot, 1816. Vultur papa
      Linnaeus, 1758 was found to be possibly based on syntypes from two different taxa
      and a lectotype is here designated. The author of Vultur sacer is Zimmermann (in
      Bartram 1793), not Cassin (1853). Possible speciation events in the genus
      Sarcoramphus are also discussed. 

PMID- 25781113
TI  - A new genus and two new species of Araecerini from high elevation in the Andes
      with a synopsis of the tribe in South America (Coleoptera, Anthribidae,
      Choraginae).
AB  - A new genus and two new species in the tribe Araecerini are described from South
      America. The new genus and species Aurigeripilus andinus gen. nov. et sp. nov.
      from high elevation (2930 m) from Colombia (PNN Chingaza Bosque Palacio) is
      described and characterized by a conspicuous antebasal carina of the pronotum.
      Neoxenus corrugatus sp. nov. is also described from Ecuador (Napo, Baeza).
      Illustrations are provided of both species. An overview with diagnostic
      characteres of South America genera of the tribe Araecerini Lacordaire is
      presented. 

PMID- 25781114
TI  - A new Mexican species of Megarthrus Curtis (Coleoptera, Staphylinidae,
      Proteininae).

PMID- 25781115
TI  - A modified cavity slide for temporary preparation and illustration of insect
      genitalia in glycerin.